PMID- 21713124
TI  - High-precision, three-dimensional tracking of mouse whisker movements with
      optical motion capture technology.
AB  - The mystacial vibrissae or whiskers in rodents are sensitive tactile hairs
      emerging from both sides of the face. Rats and mice actively move these whiskers
      during exploration. The neuronal mechanisms controlling whisker movements and the
      sensory representation of whisker tactile information are widely studied as a
      model for sensorimotor processing in mammals. Studies of the natural whisker
      movement patterns during exploration and tactile examination are still in their
      early stages. Tracking the movements of whiskers is technically challenging as
      they move relatively fast and are very thin, particularly in mice. Existing
      systems detect light-beam interruptions by the whiskers or use high-speed video
      to track whisker movements in one or two-dimensions. Here we describe a method
      for tracking the movements of mouse whiskers in three-dimensions (3D) using
      optical motion capture technology (OMCT). OMCT tracks the movements of small
      retro-reflective markers attached to whiskers of a head-fixed mouse with a
      spatial resolution of <0.5 mm in all 3D and a temporal resolution of 5 ms (200
      fps). The system stores the 3D coordinates of the marker's trajectories onto hard
      disk allowing a detailed analysis of movement trajectories bilateral
      coordination. The described method currently uses the minimum of two tracking
      cameras, which requires head-fixation for reliable tracking.

PMID- 21713125
TI  - Porcine bladder urothelial, myofibroblast, and detrusor muscle cells:
      characterization and ATP release.
AB  - ATP is released from the bladder mucosa in response to stretch, but the cell
      types responsible are unclear. Our aim was to isolate and characterize individual
      populations of urothelial, myofibroblast, and detrusor muscle cells in culture,
      and to examine agonist-stimulated ATP release. Using female pig bladders,
      urothelial cells were isolated from bladder mucosa following trypsin-digestion of
      the luminal surface. The underlying myofibroblast layer was dissected, minced,
      digested, and cultured until confluent (10-14 days). A similar protocol was used
      for muscle cells. Cultures were used for immunocytochemical staining and/or ATP
      release investigations. In urothelial cultures, immunoreactivity was present for
      the cytokeratin marker AE1/AE3 but not the contractile protein alpha-smooth
      muscle actin (alpha-SMA) or the cytoskeletal filament vimentin. Neither
      myofibroblast nor muscle cell cultures stained for AE1/AE3. Myofibroblast
      cultures partially stained for alpha-SMA, whereas muscle cultures were 100%
      stained. Both myofibroblast and muscle stained for vimentin, however, they were
      morphologically distinct. Ultrastructural studies verified that the suburothelial
      layer of pig bladder contained abundant myofibroblasts, characterized by high
      densities of rough endoplasmic reticulum. Baseline ATP release was higher in
      urothelial and myofibroblast cultures, compared with muscle. ATP release was
      significantly stimulated by stretch in all three cell populations. Only
      urothelial cells released ATP in response to acid, and only muscle cells were
      stimulated by capsaicin. Tachykinins had no effect on ATP release. In conclusion,
      we have established a method for culture of three cell populations from porcine
      bladder, a well-known human bladder model, and shown that these are distinct
      morphologically, immunologically, and pharmacologically.

PMID- 21713126
TI  - Role of Striatum in the Pause and Burst Generation in the Globus Pallidus of 6
      OHDA-Treated Rats.
AB  - Electrophysiological studies in patients and animal models of Parkinson's disease
      (PD) often reported increased burst activity of neurons in the basal ganglia.
      Neurons in the globus pallidus external (GPe) segment in 6-hydroxydopamine (6
      OHDA)-treated hemi-parkinsonian rats fire with strong bursts interrupted by
      pauses. The goal of this study was to evaluate the hypothesis that dopamine (DA)
      depletion increases burst firings of striatal (Str) neurons projecting to the GPe
      and that the increased Str-GPe burst inputs play a significant role in the
      generation of pauses and bursts in GPe and its projection sites. To evaluate this
      hypothesis, the unitary activity of Str and GPe was recorded from control and 6
      OHDA-treated rats anesthetized with 0.5-1% isoflurane. The occurrence of pauses
      and bursts in the firings of GPe neurons was significantly higher in 6-OHDA than
      in normal rats. Muscimol injection into the Str of 6-OHDA rats increased average
      firing rate and greatly reduced the pauses and bursts in GPe. Recordings from Str
      revealed that most of the presumed projection neurons in control rats have very
      low spontaneous activity, and even the occasional neurons that did exhibit
      spontaneous burst firings did so with an average rate of less than 2 Hz. In DA
      depleted Str, neurons having stronger bursts and a higher average firing rate
      were encountered more frequently. Juxtacellular labeling revealed that most of
      these neurons were medium spiny neurons projecting only to GPe. Injection of a
      behaviorally effective dose of methyl-l-DOPA into the Str of 6-OHDA rats
      significantly increased the average firing rate and decreased the number of
      pauses of GPe neurons. These data validate the hypothesis that DA-depletion
      increases burst firings of Str neurons projecting to the GPe and that the
      increased Str-GPe burst inputs play a significant role in the generation of
      pauses and bursts in GPe. These results suggest that treatment to reduce burst
      Str-GPe inhibitory inputs may help to restore some PD disabilities.

PMID- 21713127
TI  - Cost-utility analysis: current methodological issues and future perspectives.
AB  - The use of cost-effectiveness as final criterion in the reimbursement process for
      listing of new pharmaceuticals can be questioned from a scientific and policy
      point of view. There is a lack of consensus on main methodological issues and
      consequently we may question the appropriateness of the use of cost-effectiveness
      data in health care decision-making. Another concern is the appropriateness of
      the selection and use of an incremental cost-effectiveness threshold (Cost/QALY).
      In this review, we focus mainly on only some key methodological concerns relating
      to discounting, the utility concept, cost assessment, and modeling methodologies.
      Finally we will consider the relevance of some other important decision criteria,
      like social values and equity.

PMID- 21713128
TI  - Modality Switching in a Property Verification Task: An ERP Study of What Happens
      When Candles Flicker after High Heels Click.
AB  - The perceptual modalities associated with property words, such as flicker or
      click, have previously been demonstrated to affect subsequent property
      verification judgments (Pecher et al., 2003). Known as the conceptual modality
      switch effect, this finding supports the claim that brain systems for perception
      and action help subserve the representation of concepts. The present study
      addressed the cognitive and neural substrate of this effect by recording event
      related potentials (ERPs) as participants performed a property verification task
      with visual or auditory properties in key trials. We found that for visual
      property verifications, modality switching was associated with an increased
      amplitude N400. For auditory verifications, switching led to a larger late
      positive complex. Observed ERP effects of modality switching suggest property
      words access perceptual brain systems. Moreover, the timing and pattern of the
      effects suggest perceptual systems impact the decision-making stage in the
      verification of auditory properties, and the semantic stage in the verification
      of visual properties.

PMID- 21713129
TI  - Biology of consciousness.
AB  - The Dynamic Core and Global Workspace hypotheses were independently put forward
      to provide mechanistic and biologically plausible accounts of how brains generate
      conscious mental content. The Dynamic Core proposes that reentrant neural
      activity in the thalamocortical system gives rise to conscious experience. Global
      Workspace reconciles the limited capacity of momentary conscious content with the
      vast repertoire of long-term memory. In this paper we show the close relationship
      between the two hypotheses. This relationship allows for a strictly biological
      account of phenomenal experience and subjectivity that is consistent with
      mounting experimental evidence. We examine the constraints on causal analyses of
      consciousness and suggest that there is now sufficient evidence to consider the
      design and construction of a conscious artifact.

PMID- 21713130
TI  - Children's Brain Development Benefits from Longer Gestation.
AB  - Disruptions to brain development associated with shortened gestation place
      individuals at risk for the development of behavioral and psychological
      dysfunction throughout the lifespan. The purpose of the present study was to
      determine if the benefit for brain development conferred by increased gestational
      length exists on a continuum across the gestational age spectrum among healthy
      children with a stable neonatal course. Neurodevelopment was evaluated with
      structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year
      old children born between 28 and 41 gestational weeks with a stable neonatal
      course. Data indicate that a longer gestational period confers an advantage for
      neurodevelopment. Longer duration of gestation was associated with region
      specific increases in gray matter density. Further, the benefit of longer
      gestation for brain development was present even when only children born full
      term were considered. These findings demonstrate that even modest decreases in
      the duration of gestation can exert profound and lasting effects on
      neurodevelopment for both term and preterm infants and may contribute to long
      term risk for health and disease.

PMID- 21713132
TI  - Anger and the speed of full-body approach and avoidance reactions.
AB  - The notion that anger is linked to approach motivation received support from
      behavioral studies, which measured various motor responses to angering stimuli.
      However, none of these studies examined full-body motions which characterize many
      if not most everyday instances of anger. The authors incorporate a novel
      behavioral motor task that tests motivational direction by measuring the reaction
      times (RTs) of stepping forward and backward in response to the words "toward"
      and "away." The results show that, relative to anxiety and control conditions,
      anger induction resulted in a steeper approach-avoidance RT gradient which was
      shifted in favor of approach.

PMID- 21713131
TI  - Men fear other men most: gender specific brain activations in perceiving threat
      from dynamic faces and bodies - an FMRI study.
AB  - Gender differences are an important factor regulating our daily interactions.
      Using functional magnetic resonance imaging we show that brain areas involved in
      processing social signals are activated differently by threatening signals send
      from male and female facial and bodily expressions and that their activation
      patterns are different for male and female observers. Male participants pay more
      attention to the female face as shown by increased amygdala activity. But a host
      of other areas show selective sensitivity for male observers attending to male
      threatening bodily expressions (extrastriate body area, superior temporal sulcus,
      fusiform gyrus, pre-supplementary motor area, and premotor cortex). This is the
      first study investigating gender differences in processing dynamic female and
      male facial and bodily expressions and it illustrates the importance of gender
      differences in affective communication.

PMID- 21713133
TI  - Secondary metabolites and bioactivities of Myrtus communis.
AB  - BACKGROUND: Myrtus species are characterized by the presence of phenolic acids,
      flavonoids, tannins, volatile oils and fatty acids. They are remedies for variety
      of ailments. This study therefore investigated medicinal effects of Myrtus
      communis L. METHODS: Bioactivity studies of Myrtus communis L. leaves were
      carried out on volatile oil, 7% methanol and aqueous extracts and the isolated
      compounds myricetin 3-O-beta-glucopyranoside, myricetin 3-O-?-rhamnopyranoside
      and gallic acid. RESULTS: Determination of the median lethal dose (LD(50))
      revealed that the volatile oil, alcoholic and aqueous extracts were practically
      nontoxic and highly safe as no lethality was observed. The tested materials
      (volatile oil, alcoholic and aqueous extracts, myricetin 3-O-beta
      glucopyranoside, myricetin 3-O-?-rhamnopyranoside and gallic acid) showed
      significant antihyperglycemic, anti-inflammatory and antinociceptive effects as
      compared with control groups and reference drugs. CONCLUSION: Administration of
      extracts of M. communis leaves could be safe at the dose used in this study.

PMID- 21713134
TI  - Effect of nanohypericum (Hypericum perforatum gold nanoparticles) treatment on
      restraint stressinduced behavioral and biochemical alteration in male albino
      mice.
AB  - BACKGORUND: Hypericum perforatum extract (HPE), is known for its antidepressant
      effect. METHODS: In the present study we investigated the effect of H. perforatum
      gold nanoparticles (Nanohypericum-HPGNPs) protective role against restraint
      stress-induced behavioral and biochemical alterations in mice. Animals were
      immobilized for a period of 6 hrs/day. HPE (200 mg/kg) and nanohypericum (20
      mg/kg) were administered 30 minutes before the animals were subjected to acute
      immobilized stress. Behavioral test parameters for anxiety and spatial memory
      were assessed followed by biochemical parmeters (lipid peroxidation, super oxide
      dismutase, catalase, glutathione peroxidase, reduced glutathione, etc.)
      subsequently. RESULTS: The behavior study showed severe anxiety and memory loss
      compared to unstressed animals. Biochemical analyses revealed an increase in
      lipid per oxidation, depletion of super oxide dismutase, reduced glutathione,
      catalase activity and glutathione per oxidase as compared to unstressed animal.
      Twenty one days of H. perforatum and nanohypericum treatment in a dose of 200
      mg/kg and 20 mg/kg, respectively, significantly attenuated restraint stress
      induced behavioral and oxidative damage. CONCLUSION: In conclusion nanohypericum
      prove the modest activity than the HPE.

PMID- 21713135
TI  - A comparison of the cytotoxic potential of standardized aqueous and ethanolic
      extracts of a polyherbal mixture comprised of Nigella sativa (seeds), Hemidesmus
      indicus (roots) and Smilax glabra (rhizome).
AB  - BACKGROUND: A decoction (hot-water extract) comprised of Nigella sativa (seeds),
      Hemidesmus indicus (roots), and Smilax glabra (rhizome) has been reported to
      prevent chemically-induced hepatocarcinogenic changes in rats and to exert
      significant cytotoxic effects on human hepatoma (HepG2) cells. However, the
      decoction used in previous studies to determine cytotoxicity was not
      standardized. Further, during preparation of pharmaceuticals for clinical use, it
      is more convenient to use an ethanolic extract. Therefore this study was carried
      out to (a) develop standardized aqueous and ethanolic extracts of the plant
      mixture (N. sativa, H. indicus, and S. glabra) used in the preparation of the
      original decoction, and (b) compare the cytotoxic effects of these two extracts
      by evaluating cytotoxicity to the human hepatoma (HepG2) cell line. METHODS:
      Aqueous and ethanolic extracts have been standardized by evaluating organoleptic
      characters, physicochemical properties, qualitative and quantitative analysis of
      chemical constituents, and analysis of High Performance Liquid Chromatography
      (HPLC) and Thin Layer Chromatography (TLC) profiles. Cytotoxic potentials of the
      above standardized extracts were compared by evaluating their effects on the
      survival and overall cell activity of HepG2 cells by use of the 3-(4, 5
      dimethylthiazol-2yl) -2, 5 - biphenyl tetrazolium bromide (MTT) and
      Sulphorhodamine B (SRB) assays. RESULTS: Results from MTT and SRB assays
      demonstrated that both extracts exerted strong dose-dependent in vitro
      cytotoxicity to HepG2 cells. The standardized aqueous extract showed a marginally
      (though significantly, P<0.05) higher cyotoxic potential than the ethanolic
      extract. Thymoquinone, an already known cytotoxic compound isolated from N.
      sativa seeds was only observed in the standardized ethanolic extract. Thus,
      compounds other than thymoquinone appear to mediate the cytotoxicity of the
      standardized aqueous extract of this poly-herbal preparation. CONCLUSION: It may
      be concluded that results obtained in the present study could be used as a
      diagnostic tool for the correct identification of these aqueous or ethanolic
      extracts and would be useful for the preparation of a standardized pharmaceutical
      product that may be used in the future for clinical therapy of hepatocellular
      carcinoma.

PMID- 21713136
TI  - Isolation and characterization of phytoconstituents from Chlorophytum
      borivilianum.
AB  - BACKGROUND: The present communication deals with the identification and
      characterization of bioactive principles from the roots of Chlorophytum
      borivilianum. METHOD: Methanolic extract and its fractions were used to isolate
      different phytoconstituents. The structures of isolated compounds were
      characterized and elucidated with chemical and spectroscopic techniques such as
      Infra Red, Nuclear Mass Resonace and Mass spectroscopy experiments. Fatty acids
      were characterized by GC-MS analysis. RESULT: Three Fatty acids were isolated and
      confirmed. One sterol stigmasterol was isolated. One new saponin named as
      Chlorophytoside-I (3beta, 5alpha, 22R, 25R)-26-(beta-D-glucopyranosyloxy)-22
      hydroxy-furostan-12-one-3 yl O-beta-D-galactopyranosyl (1-4) glucopyranoside was
      isolated. CONCLUSION: The roots of Chlorophytum borivilianum contain three
      important fatty acids, common sterol stigmasterol and one furostanol saponins.

PMID- 21713137
TI  - Possible implication of oxidative stress in anti filarial effect of certain
      traditionally used medicinal plants in vitro against Brugia malayi microfilariae.
AB  - INTRODUCTION: Tropical disease research scheme of World Health Organization has
      duly recognized traditional medicine as alternative for antifilarial drug
      development. Polyphenolic compounds present in traditionally used herbal
      medicines are natural antioxidants; however, paradoxically they may exert pro
      oxidant effect. Popular drug diethyl carbamazine citrate harnesses the innate
      inflammatory response and the consequent oxidative assault to combat invading
      microbes. METHODS: With this perspective, extracts of Vitex negundo L. (roots),
      Butea monosperma L. (leaves), Aegle marmelos Corr. (leaves), and Ricinus communis
      L. (leaves) were selected to explore the possible role of oxidative rationale in
      the antifilarial effect in vitro. RESULTS: Apart from the last, other three plant
      extracts were reported to have polyphenolic compounds. Dose-dependent increase
      was found in the levels of lipid peroxidation and protein carbonylation for all
      the three plant extracts except Ricinus communis L. (leaves). Such increase in
      oxidative parameters also showed some degree of plant-specific predilection in
      terms of relatively higher level of particular oxidative parameter. High degree
      of correlation was observed between the antifilarial effect and the levels of
      corresponding oxidative stress parameters for these three plants. However,
      extracts of Ricinus communis L. (leaves) which is relatively deficient in
      polyphenolic ingredients recorded maximum 30% loss of motility and also did not
      show any significant difference in various stress parameters from corresponding
      control levels. CONCLUSION: These results reveal that targeted oxidative stress
      might be crucial in the pharmacodynamics.

PMID- 21713138
TI  - Evaluation of in vitro cytotoxic effect of Trichosanthes dioica root.
AB  - BACKGROUND: Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in
      English is a dioecious climber grown in India and used traditionally for various
      medicinal purposes. METHODS: Present study was aimed to evaluate in vitro
      cytotoxic effect of dichloromethane (DCTD), methanol (METD), and aqueous (AQTD)
      extracts of T. dioica root using Allium cepa root meristems by keeping them in
      different concentrations of each test extract under specific experimental
      conditions followed by determination of root growth inhibition (root length and
      number) and mitotic index. RESULTS: All the extracts significantly demonstrated
      concentration-dependent inhibition of root length and number and reduction in
      mitotic index, indicating antimitotic activity demonstrating cytotoxicity and
      genotoxicity. DCTD was found to be the most potent (EC(50) : 2.8 mg/ml), followed
      by METD and AQTD. CONCLUSION: The present study therefore, establishes promising
      in vitro cytotoxic and genotoxic property of T. dioica root against the test
      system.

PMID- 21713139
TI  - Modulating effect of Gmelina arborea Linn. on immunosuppressed albino rats.
AB  - AIM: In the present study, the immunomodulatory effects of roots of Gmelina
      arborea Linn. were investigated MATERIALS AND METHODS: Methanolic extract of G.
      arborea Linn. (MEGA) and its ethyl acetate fraction (EAFME) were used for
      evaluating the pharmacological activity. The modulating effect was evaluated on
      humoral and cell-mediated immune response using animal models like
      cyclophosphamide-induced myelosuppression, delayed-type hypersensitivity (DTH)
      response, and humoral antibody (HA) titre RESULTS: Both test extracts produced
      significant increase in HA titre, DTH response, and levels of total white blood
      cell count CONCLUSION: This drug is found to be a potential immunostimulant.

PMID- 21713140
TI  - Anti-inflammatory activity of aqueous extract of Mirabilis jalapa Linn. leaves.
AB  - BACKGROUND: Theobjective of the present study was to evaluate the anti
      inflammatory activity of aqueous extract of Mirabilis jalapa Linn.
      (MJL)(Nyctaginaceae) leaves for scientific validation of the folklore claim of
      the plant. The leaves are used as traditional folk medicine in the south of
      Brazil to treat inflammatory and painful diseases. Cosmetic or dermo
      pharmaceutical compositions containing MJL are claimed to be useful against
      inflammation and dry skin. METHODS: Aqueous extract of the leaves was prepared by
      cold maceration. RESULTS: The anti-inflammatory activity was evaluated using
      carrageenan and formalin-induced paw edema models in Wistar albino rats. The anti
      inflammatory activity was found to be dose dependent in carrageenan-induced paw
      edema model. The aqueous extract has shown significant (P < 0.05) inhibition of
      paw oedema, 37.5% and 54.0% on 4 (th) hour at the doses of 200 and 400 mg/kg,
      respectively. Similar pattern of paw edema inhibition was seen in formalin
      induced paw edema model. The maximum percentage inhibition in paw edema was 32.9%
      and 43.0% on 4 (th) day at the doses of 200 and 400 mg/kg, respectively.
      CONCLUSION: The results of present study demonstrate that aqueous extract of the
      leaves possess significant (P < 0.05) anti-inflammatory potential.

PMID- 21713141
TI  - Influence of sonication on the phenolic content and antioxidant activity of
      Terminalia catappa L. leaves.
AB  - AIM: This study was designed to evaluate the phenolic content and antioxidant
      activity of ethanolic extracts from T. catappa leaves obtained by different
      intervals of sonication. METHODS: Three commonly used methods were followed to
      evaluate phenolic content and four in vitro methods like 2,2-diphenyl-1
      picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)
      diammonium salt (ABTS) radical scavenging assay, ferric reducing antioxidant
      potency (FRAP), and total antioxidant capacity assays for measuring the
      antioxidant activities. Antioxidant values of these assays were expressed in
      terms of milligrams vitamin C equivalent (VCE) antioxidant activities. RESULTS:
      This study showed that extract obtained with 40 minutes of sonication possessed
      significant (P < 0.05) polyphenolic contents compared to 20 and 60 minutes
      sonication and control (24 hour maceration). Moreover, sonication of T. catappa
      leaf above 40 minutes was found to be unsuitable for extracting out phenolic
      contents. Even the results of antioxidant assays showed that 40 minutes of the
      sonicated extract exhibited significant (P < 0.05) VCE values compared to
      extracts obtained at different intervals of sonication and control. CONCLUSIONS:
      In sonication extraction method 40 minutes is an ideal time to obtain extract
      enriched with high polyphenolic content with good antioxidant activity from T.
      catappa leaves.

PMID- 21713142
TI  - A comparative profile of methanol extracts of Allium cepa and Allium sativum in
      diabetic neuropathy in mice.
AB  - INTRODUCTION: Diabetic Neuropathy (DN) is a major microvascular complication of
      uncontrolled diabetes. This may result from increased oxidative stress that
      accompanies diabetes. Hence plants with antioxidant action play an important role
      in management of diabetes and its complications. MATERIALS AND METHODS: This
      study was designed to evaluate preventive as well as curative effect of methanol
      extracts of outer scales and edible portions of two plants with established
      antioxidant action - Allium cepa and Allium sativum, in induced DN in albino
      mice. Mice were divided into control, diabetic and test extracts treated groups.
      Test extracts were administered daily at a dose of 200 mg/kg p.o. for 21 days, in
      the preventive group prior to onset of DN, and in the curative group after the
      onset of DN. Hyperalgesia and oxidative stress markers were assessed. STZ
      diabetic mice showed a significant thermal hyperalgesia (as assessed by the tail
      flick test), indicating development of DN. RESULTS: Treatment with test extracts
      prevented loss in body weight, decreased plasma glucose level, and significantly
      ameliorated the hyperalgesia, TBARS, serum nitrite and GSH levels in diabetic
      mice. CONCLUSION: Methanol extract of outer scales of onion has shown most
      significant improvement; may be due to higher content of phenolic compounds in
      outer scales of A. cepa.

PMID- 21713143
TI  - An automated or semi-automated identification system using venation pattern to
      delimit Indian leaf drugs: A proposal.
AB  - About 7,200 medicinal plants are known to occur in India, of which, the leaves of
      a few hundred plants have medicinal properties. Identification of leaf drugs
      using venation is considered as one of the most reliable and convenient methods.
      Leaf identification by mechanical means may often lead to wrong identification.
      Due to the growing volume of illegal trade/malpractice in the crude drug industry
      on the one hand and lack of sufficient experts on the other, a much faster,
      convenient and reliable method is mandatory for the identification of Indian leaf
      drugs. Therefore, a new automated or semi-automated identification system based
      on venation pattern is inevitable for the present day condition to identify and
      authenticate the leaves of Indian medicinal plants.

PMID- 21713144
TI  - Inhibitory effect of rutin and curcumin on experimentally-induced calcium oxalate
      urolithiasis in rats.
AB  - BACKGROUND: Renal epithelial cell injury by reactive oxygen species is pre
      requisite step in the pathogenesis of urolithiasis. Rutin and curcumin are
      polyphenolic compounds known to have antioxidant and anti-inflammatory
      activities, but their effect on urolithiasis is yet to be elucidated. In the
      present study, we have investigated the inhibitory effect of rutin and curcumin
      on calcium oxalate urolithiasis in Wistar albino rats. METHODS: Calcium oxalate
      urolithiasis was induced experimentally by administration of 0.75% v/v ethylene
      glycol with 1% w/v ammonium chloride in drinking water for three days followed by
      only 0.75% v/v ethylene glycol for 25 days. Rutin (20 mg/kg body weight) and
      curcumin (60 mg/kg body weight) were given once daily for 28 days by oral route.
      After treatment period, calcium and oxalate levels in urine and kidney tissue
      homogenate were measured. Kidney was also used for histopathological examination.
      RESULTS: Stone-induction with ethylene glycol and ammonium chloride resulted in
      elevated levels of calcium and oxalate in the urine and kidney sample, whereas
      supplementation of rutin and curcumin restored it near to normal.
      Histopathological study revealed minimum tissue damage and less number of calcium
      oxalate deposits in kidney of animal treated with rutin and curcumin as compared
      to calculi-induced animal. CONCLUSION: The data suggest that the rutin and
      curcumin inhibits calcium oxalate urolithiasis. This effect is mediated possibly
      through a lowering of urinary concentration of stone forming constituents, anti
      inflammatory and antioxidant effects.

PMID- 21713145
TI  - Ayurveda and cancer.

PMID- 21713146
TI  - Needle stick injuries during fine needle aspiration procedure: Frequency, causes
      and knowledge, attitude and practices of cytopathologists.
AB  - BACKGROUND: There is no study available on the frequency, predisposing factors
      and outcome of needle stick injury (NSI) in cytopathologists who perform fine
      needle aspiration (FNA). AIM: To know the frequency, circumstances and sequlae of
      NSI sustained by cytopathologists, assess their knowledge about risks of NSI and
      attitudes and practices towards use of standard precautions and post-injury wound
      care. MATERIALS AND METHODS:  STUDY DESIGN: cross sectional. SETTING: Tertiary
      care teaching and non-teaching hospitals and private laboratories. DATA
      COLLECTION METHOD: Knowledge, attitude and practices survey using a
      questionnaire. RESULTS: Majority (90.5%) of the respondents have had NSI in their
      total career. In the previous year, more than half (71.4%) had at least one NSI
      (mean 3.2). NSI was the most common in index finger of non-dominant hand (59.6%)
      and occurred during step two of FNA procedure when the needle was being
      manipulated within the lump. The major predisposing factors were uncooperative
      patients (88.9%), small children (54%), deep masses (36.5%), hot humid climate
      (88.9%), heavy workload (76.2%) and poor administrative arrangement (54%). The
      adherence to standard precautions was not optimal (74.6%). None of them reported
      NSI to the authorities, nor investigated source patient or themselves. 82.5% of
      the respondents were not aware of any formal exposure reporting system in their
      hospital. CONCLUSION: Cytopathologists frequently experience NSI while performing
      FNA. Frequency of injury is also related to patient characteristics and work site
      factors. Education and motivation for adhering to standard precautions and post
      exposure prophylaxis are often lacking.

PMID- 21713147
TI  - Her-2 neu (Cerb-B2) expression in fine needle aspiration samples of breast
      carcinoma: A pilot study comparing FISH, CISH and immunocytochemistry.
AB  - BACKGROUND: Breast cancers with Her-2 neu gene amplification are recognized as
      important markers for aggressive disease and targets which respond to therapy
      with trastuzumab. Her-2 neu testing on histological sections is routinely
      performed to select patients who may benefit from anti- Her-2 neu therapy. Few
      reports are available which document Her-2 neu status on fine needle aspirates
      (FNA). AIM: This pilot study is to document expression of Her-2 neu (Cerb-B2) on
      cytospin smears from FNA of patients with breast carcinoma. MATERIALS AND
      METHODS: Twenty samples of FNA already collected for diagnostic purposes from
      patients with primary breast carcinoma were studied for demonstration of Her-2
      neu expression by immunohistochemistry (IHC), Fluorescent in-situ hybridization
      (FISH) and chromogenic in-situ hybridization (CISH) on cytospin smears from FNA.
      Their expression was compared with tissue sections where possible. RESULTS: Good
      correlation was observed between Her-2 neu protein expression and gene
      amplification in cytospin smears. Three of five (60%) breast carcinomas cases
      with 2+ and 3+ staining on IHC showed gene amplification by FISH and CISH. Three
      of 7 (43%) and 5 of 7 (71%) cases negative/1+ staining on IHC did not show gene
      amplification by FISH and CISH respectively. Tissue sections from 10 cases with
      2+ and 3+ staining for Her2neu by IHC showed gene amplification in 8 cases.
      CONCLUSION: Demonstration of Her-2 neu by IHC, FISH or CISH in FNA is possible
      and may play a role in the management of patients with advanced breast cancer or
      those cases where surgical resection is not advisable.

PMID- 21713148
TI  - Cell Cannibalism: A cytological study in effusion samples.
AB  - BACKGROUND: Cytological examination of effusion fluid is a relatively easy and
      quick method for the diagnosis of primary or secondary malignancy. AIMS: To
      analyze the cytological significance of cell cannibalism in malignant effusion
      samples. MATERIALS AND METHODS: A retrospective review of 100 cases of malignant
      effusion was done. These 100 cases included 50 cases of contiguous, local spread
      to pleural/ascitic fluid. The remaining 50 cases were of disseminated malignancy.
      Effusions due to hematolymphoid malignancies were excluded. Smears from these
      cases were assessed for the presence of cell cannibalism, tumor cell within a
      tumor cell. RESULTS: The cannibalistic cells were more common in effusions with
      disseminated malignancy (nine out of 50 cases i.e. 18%) compared with cases of
      contiguous, local spread (two out of 50 cases i.e. 4%). Chi square test showed
      this difference to be statistically significant (x(2) 5.005, P=0.025). The
      majority of the cases were of carcinoma lung (6/11). Cytomorphologically,
      histiocytes displaying phagocytosis can simulate tumor cells and need to be
      distinguished. CONCLUSIONS: Presence of cell cannibalism in malignant effusions
      is more often an indicator of disseminated malignancy with secondaries and higher
      tumor stage. Furthermore, cannibalism may provide a reliable predictor of
      progression of tumor from primary to the metastatic site.

PMID- 21713149
TI  - FNAB of metastatic lesions with special reference to clinicopathological analysis
      of primary site in cases of epithelial and non-epithelial tumors.
AB  - AIMS: To ascertain the cytological diagnosis of metastatic lesions with special
      reference to the clinicopathological analysis of the primary site in cases of
      epithelial and non-epithelial tumors. MATERIALS AND METHODS: One hundred seventy
      one suspected metastatic lesions were aspirated with a 22-23G needle and the
      smears were fixed and stained. The cases in which the primary site was not
      evident at the time of initial presentation were subsequently subjected to
      thorough physical examination followed by radiological investigations for the
      search of the primary site. Histopathological examination was performed in 16
      cases with inconclusive cytological impression. OBSERVATIONS: Of the total cases
      of metastatic lesions, 155 cases (90.6%) were diagnosed by fine needle aspiration
      biopsy and 16 cases (9.4%) by histopathology. The majority of the cases, 81
      (47.4%), were observed in the fifth decade of life, followed by 76 cases (44.4%)
      in the sixth decade and 11 cases (6.4%) in the seventh decade of life. Lymph
      nodes were the most frequent site of metastasis in 115 cases (67.3%), with the
      majority in the cervical group. The oropharynx, including the oral cavity and
      pharyngolarynx, was observed to be the most common primary site, 55 cases
      (32.2%). CONCLUSION: The most critical aspect of the evaluation of metastatic
      cases is the accurate pathologic assessment of the malignant tissues in
      conjunction with pertinent clinical data. Such close collaboration between the
      clinician and the pathologist may maximize the diagnostic potential in treatable
      primary tumors.

PMID- 21713151
TI  - Intraparenchymal clear cell ependymoma.
AB  - Clear cell ependymoma (CCE) is an uncommon variant of ependymoma having a
      predilection for the supratentorial region. Histologically, it bears an uncanny
      resemblance to oligodendroglioma, central neurocytoma, hemangioblastoma and
      metastasis from clear cell carcinoma. Here, we report a rare case of clear cell
      ependymoma in a 45-year-old male, which histomorphologically resembled anaplastic
      oligodendroglioma on intraoperative smears, frozen section and routine light
      microscopy. Immunohistochemistry, however, helped to arrive at the correct
      diagnosis. Unlike other clear cell tumors of the brain parenchyma, CCE is known
      to follow an aggressive course and, hence, obtaining a correct diagnosis is
      imperative since it has a direct therapeutic and prognostic connotation.

PMID- 21713150
TI  - Quantitative cytomorphometric analysis of exfoliated normal gingival cells.
AB  - BACKGROUND: The use of oral exfoliative cytology as a diagnostic aid accentuates
      the need for establishing an accurate baseline, thereby enabling the comparison
      of abnormal oral tissue with established baseline. AIMS AND OBJECTIVE: To detect
      any changes in the nuclear area (NA), cytoplasmic area (CA), and
      nuclear:cytoplasmic ratio (N:C ratio) values for clinically normal gingival
      smears in relation to age and sex of apparently healthy subjects. MATERIALS AND
      METHODS: Gingival smears were collected from 80 (40 male, 40 female) apparently
      healthy subjects belonging to the age group of 0-20, 21-40, 41-60, and more than
      60 years. Smear slides were fixed by using spray fixative. The smears were
      stained using Papanicolaou procedure. The cytoplasmic and NAs were measured using
      image analysis software. Statistical analysis of the data was done using one-way
      ANOVA with Tukey-HSD procedure and Student's t test. RESULTS: The result showed
      that there was a significant difference (P<0.001) in NA, CA, and N:C in males of
      different age groups. There was a significant difference (P<0.001) in NA, CA, and
      N:C in females of different age groups. The difference in N:C between males and
      females was significant (P<0.001) in all the groups. The difference in NA, CA,
      and N:C with age irrespective of gender was significant (P<0.05). There was a
      significant difference (P<0.05) between males and females with respect to NA, CA,
      and N:C irrespective of age. CONCLUSION: Age-and sex-related alterations were
      observed in gingival smears, which could be a baseline for these variables to
      compare identical measurements, made on pathologic smears of oral premalignant
      and malignant lesions.

PMID- 21713152
TI  - Imprint cytology of the chromophobe renal cell carcinoma: Correlation with the
      histological and ultrastructural features.
AB  - Chromophobe renal cell carcinoma (ChRCC) is a unique entity of renal cell
      carcinoma and has a low malignant potential. A correct cytological diagnosis can
      help to decide the suitable management and operation. I present here a case with
      an imprint cytology of ChRCC focusing on the correlation with the histological
      and ultrastructural features. A 69-year-old male underwent partial nephrectomy
      and imprint cytology. The cellular smear consisted of predominantly granular
      eosinophilic cells with round nuclei, a well-defined cytoplasmic membrane and
      accentuated cell borders. The cytoplasm was characterized by variable granularity
      with reticulated clearing or vague perinuclear vacuolization. Distinct
      perinuclear halos were infrequently noted. The histological, immunohistochemical
      and ultrastructural findings were compatible with ChRCC.

PMID- 21713153
TI  - Fine-needle aspiration diagnosis of extranodal non-Hodgkin's lymphoma of the
      tongue.
AB  - Primary non-Hodgkin's lymphoma (NHL) of the oral region is rare. Oral
      manifestation is present in 3-5% of cases of NHL and oral lesions are rarely the
      initial manifestations. We describe primary NHL, diffuse, mixed, small and large
      cell type in a 50-year-old female, who presented with mass lesion primarily
      involving the base of the tongue; initially diagnosed by fine needle aspiration
      cytology and later confirmed by histopathology and immunohistochemistry.
      Pertinent literature is being reviewed.

PMID- 21713154
TI  - Mucinous carcinoma in a male breast.
AB  - Male breast cancer is rare as compared to female counterpart. Pure mucinous
      carcinoma is an extremely rare histological subtype representing less than 1% of
      male breast cancers. So far very few cases of pure mucinous carcinoma of male
      breast have been reported in the literature, most of which were diagnosed after
      surgical resection. Fine-needle aspiration cytology is a well-established
      procedure for the evaluation of female breast masses but the diagnosis of
      malignancy in aspirates from male breast masses is rare. We herein present one
      case of mucinous carcinoma of breast in a 75-year-old male diagnosed by fine
      needle aspiration and confirmed by histopathology. After a follow-up of 12 months
      the patient is free of any recurrence or metastasis.

PMID- 21713155
TI  - Cytologic features of abscessified anaplastic large cell lymphoma.

PMID- 21713156
TI  - Schaumann body in a case of sarcoidosis diagnosed on transbronchial FNAC.

PMID- 21713157
TI  - Presacral chordoma diagnosed by transrectal fine-needle aspiration cytology.

PMID- 21713158
TI  - Reconstructions of eyelid defects.
AB  - Eyelids are the protective mechanism of the eyes. The upper and lower eyelids
      have been formed for their specific functions by Nature. The eyelid defects are
      encountered in congenital anomalies, trauma, and postexcision for neoplasm. The
      reconstructions should be based on both functional and cosmetic aspects. The
      knowledge of the basic anatomy of the lids is a must. There are different
      techniques for reconstructing the upper eyelid, lower eyelid, and medial and
      lateral canthal areas. Many a times, the defects involve more than one area. For
      the reconstruction of the lid, the lining should be similar to the conjunctiva, a
      cover by skin and the middle layer to give firmness and support. It is important
      to understand the availability of various tissues for reconstruction. One layer
      should have the vascularity to support the other layer which can be a graft. A
      proper plan and execution of it is very important.

PMID- 21713159
TI  - Bleomycin: A worthy alternative.
AB  - CONTEXT: Lymphangiomas are developmental anomalies presenting mainly in the first
      two years of life. Surgical excision has been the mainstay of treatment; however
      a potentially disfiguring surgery along with presence of important structures in
      the vicinity and infiltration into surrounding structures makes the dissection
      difficult. AIMS: To study the safety and efficacy of Bleomycin as a sclerosing
      agent for lymphatic malformations in children. SETTINGS AND DESIGN: Prospective
      non comparative nonrandomized trial. MATERIALS AND METHODS: The study was carried
      out in 15 children between Day 5 of life to 12 years of age who presented between
      May2008 to May 2009. Bleomycin aqueous solution was injected intralesionally at a
      dose not exceeding 0.6 to 0.8 mg. /kg Body wt. The response to therapy was
      monitored clinically by measuring the length, breadth and area as well as by
      measuring the two largest perpendicular dimensions. The response was graded as
      excellent [total disappearance], good [>50% reduction] and poor [<50% decrease].
      Those patients with diffuse lymphangiomas associated predominantly with
      hemangiomatous malformations, mediastinal, spinal or retroperitoneal extensions,
      visceral lymphangiomas, those with infections were excluded from the study.
      STATISTICAL ANALYSIS USED: None applicable. RESULTS: The reduction in the size of
      the mass usually took between two weeks to ten months. The average duration of
      follow up has been ten months. A significant response was seen in 8 out of the
      fifteen [53.33%] patients. 5 patients [33.33%] patients showed a good response to
      therapy and achieved >50% reduction in the size of their swellings. 2 patients
      [13.33%] showed a poor response to therapy and achieved less than 50% reduction
      in the size of the swelling. Complications of the therapy were few and far
      between. 2 patients developed fever after injection, one patients reported a
      transient increase in size of swelling, 2 patients have developed discoloration
      of the overlying skin and are currently being followed up for final outcome. None
      of the patients developed leucopenia or leukocytosis. All of the complications
      were managed with conservatively. Patients are on long term follow up to evaluate
      long term effects, if any.

PMID- 21713160
TI  - Is Bleomycin a worthy alternative?

PMID- 21713161
TI  - Effect of static wrist position on grip strength.
AB  - BACKGROUND: Grip strength after wrist arthrodesis is reported to be significantly
      less than normal. One of the reasons suggested for this decrease in grip strength
      is that the arthrodesis was performed in a suboptimal position. However, there is
      no consensus on the ideal position of wrist fusion. There is a paucity of studies
      evaluating the effect of various fixed positions of the wrist on grip strength
      and therefore, there is no guide regarding the ideal position of wrist fusion.
      The authors' aim was to determine the grip strength in various fixed positions of
      the wrist and subsequently to find out in which position of wrist fusion the grip
      strength would be maximal. MATERIALS AND METHODS: One hundred healthy adults
      participated in the study. For the purpose of this study, the authors constructed
      splints to hold the wrist in five different fixed positions: 45, 30 and 15
      degrees of wrist extension, neutral and 30 degrees of wrist flexion. The grip
      strength in all the participants was measured bilaterally, first without a splint
      and then with each splint sequentially. RESULTS: The average grip strength
      without the splint was 34.3 kg for right and 32.3 kg for the left hand. Grip
      strength decreased by 19-25% when the wrist was splinted. The maximum average
      grip strength with a splint on was recorded at 45 degrees of extension (27.9 kg
      for right and 26.3 kg for left side). There was a gradual increase in the grip
      strength with increase in wrist extension but the difference was not
      statistically significant (P = 0.29). The grip strength was significantly less in
      flexed position of the wrist (P < 0.001).

PMID- 21713162
TI  - Reconstruction of severe hand contractures: An illustrative series.
AB  - AIM: An overview of a series of severe burn contractures in 44 hands
      reconstructed over a 20 month period with an easy to follow algorithm. SETTINGS
      AND DESIGN: The series was carried out by a single surgeon at Green Pastures
      Rehabilitation Centre in Pokhara, Nepal. All patients attending with severe burn
      contractures to the hand were included in the series. MATERIALS AND METHODS: This
      is a retrospective review of burn contractures in a total of 44 hands. All the
      contractures involved limitation of movement by 60 degrees in two or more joints
      or by 80 degrees in one joint. The decision making process is presented as a flow
      chart indicating when and which flaps were used. RESULTS: Illustrations
      demonstrate what was achieved, with all hands obtaining an improvement in
      function. CONCLUSIONS: Although many of these contractures can be dealt with by
      skin grafting the series clearly illustrates the indications for flap coverage.

PMID- 21713163
TI  - Use of preputial skin for coverage of post-burn contractures of fingers in
      children.
AB  - OBJECTIVE: Hand burns are common injuries. Children frequently sustain burn
      injuries, especially to their hands. Contractures are a common sequel of severe
      burns around joints. The prepuce, or foreskin, has been used as a skin graft for
      a number of indications. We conducted this study to evaluate the feasibility of
      utilising the preputial skin for the management of post-burn contractures of
      fingers in uncircumcised male children. MATERIALS AND METHODS: Preputial skin was
      used for the coverage of released contractures of fingers in 12 patients aged 2-6
      years. The aetiology of burns was "Kangri" burn in eight patients and scalding in
      four patients. Six patients had contracture in two fingers, four patients in one
      finger, and two patients had contractures in three fingers. RESULTS: None of the
      patients had graft loss, and all the wounds healed within 2 weeks. All patients
      had complete release of contractures without any recurrence. Hyperpigmentation of
      the grafts was observed over a period of time, which was well accepted by the
      parents. CONCLUSIONS: Preputial skin can be used successfully for male children
      with mild-to-moderate contractures of 2-3 fingers for restoration of the hand
      function, minimal donor site morbidity.

PMID- 21713164
TI  - Role of platysma muscle flap in depressed scars of neck.
AB  - BACKGROUND: Depressed scars in the neck pose a cosmetic problem. There is a need
      to fill the lost tissue volume defect between the surface and deeper tissues. It
      is preferable that the filling is done by autologous tissue which is available in
      substantial amount in the adjoining area. There should be no donor site
      morbidity. Platysma muscle flap meets these criteria. MATERIALS AND METHODS:
      Platysma muscle flap was advanced into the defect after excision of depressed
      scar. The procedure was done under local anesthetic in two patients. RESULT: The
      result was a 'good scar' with scar lying in the transversely oriented neck lines.
      CONCLUSIONS: Platysma muscle flap has a definitive role in revision surgery of
      depressed scars in neck as it provides an ideal tissue for lost tissue volume.

PMID- 21713165
TI  - A modified technique for nipple-areola complex reconstruction.
AB  - BACKGROUND: From a historical perspective, many techniques of nipple
      reconstruction have been performed, including a graft from the contralateral
      nipple, composite grafts such as toe pulp or earlobe tissue and even an intra
      dermal tattoo alone. This is the final stage of breast reconstruction, and is
      carried out only when the surgeon is confident that acceptable symmetry and shape
      of the reconstructed breast has been achieved. The technical challenges of nipple
      reconstruction include correcting position, maintaining adequate projection and
      creating an inconspicuous scar. An alternative to a surgically reconstructed
      nipple is the use of silicone prosthetic nipples. MATERIALS AND METHODS: From
      August 2006 until September 2007, 80 cases of nipple/areola reconstruction were
      performed in our department (UDINE UNIV.) following mammary reconstruction or
      conservative breast surgery. Forty cases were carried out with the classical
      technique and another 40 cases with the introduction of our modification in the
      form of deepithelization of a semicircular area of the adjacent skin at the base
      of the flap. Postoperative follow-up as regards the nipple size, site,
      projection, symmetry and donnar scar were assessed. Patient satisfaction was also
      addressed and evaluated. RESULTS: There were good to excellent results as regards
      nipple size, symmetry and projection. The technique is suitable for different
      autologous and implant reconstruction. The technique is an outpatient procedure,
      is easy and is not consuming time. Areolar graft from the contra-lateral areola
      is colouur matching and shows nearly no deference from the opposite one.
      CONCLUSIONS: Simple technique and not time consuming. Maintains the consistency
      and projection of the new nipple. Patient satisfaction. Minimal complication.

PMID- 21713166
TI  - Cross-chest liposuction in gynaecomastia.
AB  - BACKGROUND: Gynaecomastia is usually treated with liposuction or liposuction with
      excision of the glandular tissue. The type of surgery chosen depends on the grade
      of the condition. OBJECTIVE: Because gynaecomastia is treated primarily as a
      cosmetic procedure, we aimed at reducing the invasiveness of the surgery.
      MATERIALS AND METHODS: The technique complies with all recommended protocols for
      different grades of gynaecomastia. It uses liposuction, gland excision, or both,
      leaving only minimal post-operative scars. The use of cross-chest liposuction
      through incisions on the edge of the areola helps to get rid of all the fat under
      the areola without an additional scar as in the conventional method. RESULTS:
      This is a short series of 20 patients, all with bilateral gynaecomastia (i.e., 40
      breasts), belonging to Simon's Stage 1 and 2, studied over a period of 2 years.
      The average period of follow-up was 15 months. Post-operative complications were
      reported in only two cases, with none showing long-term complications or issues
      specifically due to the procedure. CONCLUSIONS: Cross-chest liposuction for
      gynaecomastia is a simple yet effective surgical tool in bilateral gynaecomastia
      treatment to decrease the post-operative scars. The use of techniques like
      incision line drain placement and post-drain removal suturing of wounds aid in
      decreasing the scar.

PMID- 21713167
TI  - Large myelomeningocele repair.
AB  - BACKGROUND: Wound closure is accomplished in most cases of myelomeningocele (MMC)
      by undermining of the skin edges surrounding the defect. However, large defects
      cannot be closed reliably by this simple technique. Due to the technical
      challenge associated with large MMC, surgeons have devised different methods for
      repairing large defects. In this paper, we report our experience of managing
      large defects, which we believe bears a direct relationship to decrease the
      incidence of wound complications. MATERIALS AND METHODS: Forty children with
      large MMCs underwent surgical repair and represent our experience. We recommend
      using all hairy skin around the defect as a way to decrease the tension on the
      edges of the wound and the possible subsequent necrosis. It is our experience
      that vertical incision on one or two flanks parallel to the midline can decrease
      the tension of the wound. Moreover, ventriculo-peritoneal shunting for children
      who developed hydrocephalus was performed simultaneously, which constitutes
      another recommendation for preventing fluid collection and build up of pressure
      on the wound. RESULTS: Patients in this study were in the age range of 2 days to
      8 years. The most common location of MMC was in the thoracolumbar area. All but
      four patients had severe weakness in lower extremities. We used as much hairy
      skin around the MMC sac as possible in all cases. Vertical incisions on one or
      both flanks and simultaneous shunt procedure were performed in 36 patients. We
      treated children with large MMC defects with acceptable tension-free closure.
      Nonetheless, three patients developed superficial skin infection and partial
      wound dehiscence, and they were managed conservatively. CONCLUSIONS: We recommend
      using all hairy skin around the MMC defect for closure of large defects. In cases
      that were expected to be at a higher risk to develop dehiscence release incisions
      on one or two flanks towards the fascia were found to be useful. Simultaneous
      ventriculo-peritoneal shunting is also recommended in this cohort of patients,
      according to our experience. These recommendations neither prolong the time of
      surgery nor increase the cost, but facilitate a successful closure.

PMID- 21713168
TI  - The surgical treatment of Balanitis Xerotica Obliterans.
AB  - BACKGROUND: Balanitis Xerotica Obliterans (BXO) is a chronic, often progressive
      disease, which can lead to phimosis and urethral stenosis, affecting both urinary
      and sexual function. Steroid creams are usually the first-line treatment but have
      a limited role and surgical intervention is frequently necessary. Conservative
      surgical procedures (circumcision) are often preferred in the first instance with
      the premise that recurrence of disease will require a more definitive
      reconstruction. This study looked at patients with pathologically proven BXO
      referred to the Plastic Surgery Unit at James Cook University Hospital between
      2005 and 2009. The aim was to look at their management in the past and subsequent
      management by us. We also looked at whether early referral of progressive and
      recurrent BXO patients to reconstructive surgery could have prevented unnecessary
      delay in resolving symptoms at an earlier stage. MATERIALS AND METHODS: Data was
      collected retrospectively and information regarding the exact anatomical location
      affected, the extent of the disease, the referring specialty and any previous
      surgical interventions was obtained. Alterations in urinary and sexual function
      and relief of symptoms following reconstructive surgery were analysed. RESULTS:
      Of the 23 patients in the study, 43% had previous surgery and 60% of those had
      undergone two or more procedures. Twenty-one percent of patients had a history of
      BXO for over five years. Forty-seven percent of patients had alteration in their
      urinary function and 48% alteration in their sexual function due to the disease,
      prior to referral. Early results showed remarkable improvement in urinary and
      sexual function following reconstructive surgery in this group. CONCLUSIONS:
      Steroid creams have been shown to limit the progression of the disease but do not
      offer a cure in the majority of cases. Circumcision can be a curative procedure
      in early disease. Although there is conflicting evidence for treatment of
      recurring urethral strictures, repeated urethrotomy or urethral dilatation has
      poor long-term outcome. In patients with recurrent disease and associated
      complications we propose early referral to a plastic surgeon with genitourinary
      interest or reconstructive urologist for definitive treatment.

PMID- 21713169
TI  - Management of urethrocutaneous fistula after hypospadias surgery - An experience
      of thirty-five cases.
AB  - INTRODUCTION: The commonest complication following hypospadias repair is
      occurrence of urethrocutaneous fistula. The smaller fistulas (<2 mm) are easier
      to close with a simple closure whereas larger ones (>2 mm) with good vascular
      surrounding skin require a local skin flap closure for avoiding overlapping
      suture lines. For the recurrent/larger fistulas with impaired local surrounding
      skin - incidence of recurrence is significantly reduced by providing a
      waterproofing interposition layer. AIMS: To study the effect of size, location,
      number of fistulas and surrounding tissues in selecting the procedure and its
      outcome. To identify various factors involved in the recurrence and to formulate
      a management in the cases where recurrence has occurred. PATIENTS AND METHODS:
      This study of 35 cases of urethrocutaneous fistula repair was done from July 2006
      to May 2009 to achieve better results in fistula management following hypospadias
      surgery. STATISTICAL ANALYSIS USED: X(2) test and Fisher's exact test. RESULTS:
      The overall success rate for fistula repair at first attempt was 89% with success
      rates for simple closure, layered closure and closure with waterproofing layer
      being 77%,89% and 100%, respectively. The second attempt success rate at fistula
      repair for simple closure and closure with waterproofing layer were 33% and 100%,
      respectively. At third attempt the two recurrent fistulas were managed by simple
      closure with a waterproofing interposition layer with no recurrence. All the
      waterproofing procedures in this study had a success rate of 100%. CONCLUSIONS:
      The treatment plan for a fistula must be individualized based on variables which
      has an effect on the outcome of repair and to an extent dictates the type of
      repair to be performed. The significantly improved success rates with the
      addition of a waterproofing layer suggests the use of this interposition layer
      should be done at the earliest available opportunity to prevent a reccurence
      rather than to reserve it for future options.

PMID- 21713170
TI  - Facial emotion and identity processing development in 5- to 15-year-old children.
AB  - Most developmental studies of emotional face processing to date have focused on
      infants and very young children. Additionally, studies that examine emotional
      face processing in older children do not distinguish development in emotion and
      identity face processing from more generic age-related cognitive improvement. In
      this study, we developed a paradigm that measures processing of facial expression
      in comparison to facial identity and complex visual stimuli. The three matching
      tasks were developed (i.e., facial emotion matching, facial identity matching,
      and butterfly wing matching) to include stimuli of similar level of
      discriminability and to be equated for task difficulty in earlier samples of
      young adults. Ninety-two children aged 5-15 years and a new group of 24 young
      adults completed these three matching tasks. Young children were highly adept at
      the butterfly wing task relative to their performance on both face-related tasks.
      More importantly, in older children, development of facial emotion discrimination
      ability lagged behind that of facial identity discrimination.

PMID- 21713171
TI  - Students' Factors Affecting Undergraduates' Perceptions of their Teaching and
      Learning Process within ECTS Experience.
AB  - INTRODUCTION: In the present study, we investigated the potential factors that
      influenced the level of students satisfaction with the teaching-learning process
      (TLP), from the perspective of students participating in the European Credit
      Transfer System (ECTS) experience. METHOD: A total of 1490 students from the
      Universities of Almeria and Granada (Spain) participated in an evaluation of
      their class discipline area. They completed the new revised protocol for
      evaluating the ECTS experience. Analyses of variance were carried out, taking the
      following factors as independent variables: student's grade average, year in
      school, study discipline, credit load in terms of ECTS credits assigned to a
      subject, the e-learning approach. Perception of the TLP was used as the dependent
      variable. RESULTS: The data analyses showed variability of the degree of
      statistically significance among the factors that influenced students'
      perceptions of the TLP. These factors included: Student's grade average (in favor
      of high performers), year in school (in favor of earlier years), ECTS load (in
      favor of subjects with a medium load of credits), and e-learning (in favor of its
      use). These research findings provided evidence to explore the delineation of a
      potential profile of factors that trigger a favorable perception of the TLP.
      DISCUSSION AND CONCLUSION: The present findings certainly have implications to
      deepen our understanding of the core beliefs, commitment, and the experience in
      shaping the implementation of the European Higher Education Area through the
      ECTS.

PMID- 21713172
TI  - Moving beyond traditional null hypothesis testing: evaluating expectations
      directly.
AB  - This mini-review illustrates that testing the traditional null hypothesis is not
      always the appropriate strategy. Half in jest, we discuss Aristotle's scientific
      investigations into the shape of the earth in the context of evaluating the
      traditional null hypothesis. We conclude that Aristotle was actually interested
      in evaluating informative hypotheses. In contemporary science the situation is
      not much different. That is, many researchers have no particular interest in the
      traditional null hypothesis. More can be learned from data by evaluating specific
      expectations, or so-called informative hypotheses, than by testing the
      traditional null hypothesis. These informative hypotheses will be introduced
      while providing an overview of the literature on evaluating informative
      hypothesis.

PMID- 21713173
TI  - Spatial Attention is Driven by Mental Simulations.

PMID- 21713174
TI  - A conceptual model of referee efficacy.
AB  - This paper presents a conceptual model of referee efficacy, defines the concept,
      proposes sources of referee specific efficacy information, and suggests
      consequences of having high or low referee efficacy. Referee efficacy is defined
      as the extent to which referees believe they have the capacity to perform
      successfully in their job. Referee efficacy beliefs are hypothesized to be
      influenced by mastery experiences, referee knowledge/education, support from
      significant others, physical/mental preparedness, environmental comfort, and
      perceived anxiety. In turn, referee efficacy beliefs are hypothesized to
      influence referee performance, referee stress, athlete rule violations, athlete
      satisfaction, and co-referee satisfaction.

PMID- 21713176
TI  - High skies and oceans deep: polarity benefits or mental simulation?

PMID- 21713175
TI  - Modulation of visual cortical excitability by working memory: effect of luminance
      contrast of mental imagery.
AB  - Although much is known about the impact of stimulus properties such as luminance
      contrast, spatial frequency, and orientation on visually evoked neural activity,
      much less is known about how they modulate neural activity when they are
      properties of a mental image held in working memory (WM). Here we addressed this
      question by investigating how a parametric manipulation of an imagined stimulus
      attribute affects neuronal excitability in the early visual cortex. We
      manipulated luminance contrast, a stimulus property known to strongly affect the
      magnitude of neuronal responses in early visual areas. Luminance contrast
      modulated neuronal excitability, as assessed by the frequency of phosphenes
      induced by transcranial magnetic stimulation (TMS) with the exact nature of this
      modulation depending on TMS intensity. These results point to a strong overlap in
      the neuronal processes underlying visual perception and mental imagery: not only
      does WM maintenance selectively engage neurons which are tuned to the maintained
      attribute (as has previously been shown), but the extent to which those neurons
      are activated depends on the image contrast (as is the case with visually evoked
      responses). From a methodological viewpoint, these results suggest that
      assessment of visual cortical excitability using TMS is affected by the TMS
      intensity used to probe the neuronal population.

PMID- 21713177
TI  - Attributional and relational processing in pigeons.
AB  - Six pigeons were trained using a matching-to-sample procedure where sample and
      rewarded comparisons matched on both attributional (color) and relational
      (horizontal or vertical orientation) dimensions. Probes then evaluated the
      pigeons' preference to comparisons that varied in these dimensions. A strong
      preference was found for the attribute of color. The discrimination was not found
      to transfer to novel colors, however, suggesting that a general color rule had
      not been learned. Further, when color could not be used to guide responding, some
      influence of other attributional cues such as shape, but not relational cues, was
      found. We conclude that pigeons based their performance on attributional
      properties of but not on relational properties between elements in our matching
      to-sample procedure. Future studies should look at examining other attributes to
      compare attributional versus relational processing.

PMID- 21713179
TI  - Get the story straight: contextual repetition promotes word learning from
      storybooks.
AB  - Although shared storybook reading is a common activity believed to improve the
      language skills of preschool children, how children learn new vocabulary from
      such experiences has been largely neglected in the literature. The current study
      systematically explores the effects of repeatedly reading the same storybooks on
      both young children's fast and slow mapping abilities. Specially created
      storybooks were read to 3-year-old children three times during the course of 1
      week. Each of the nine storybooks contained two novel name-object pairs. At each
      session, children either heard three different stories with the same two novel
      name-object pairs or the same story three times. Importantly, all children heard
      each novel name the same number of times. Both immediate recall and retention
      were tested with a four-alternative forced-choice task with pictures of the novel
      objects. Children who heard the same stories repeatedly were very accurate on
      both the immediate recall and retention tasks. In contrast, children who heard
      different stories were only accurate on immediate recall during the last two
      sessions and failed to learn any of the new words. Overall, then, we found a
      dramatic increase in children's ability to both recall and retain novel name
      object associations encountered during shared storybook reading when they heard
      the same stories multiple times in succession. Results are discussed in terms of
      contextual cueing effects observed in other cognitive domains.

PMID- 21713178
TI  - The nature of consciousness in the visually deprived brain.
AB  - Vision plays a central role in how we represent and interact with the world
      around us. The primacy of vision is structurally imbedded in cortical
      organization as about one-third of the cortical surface in primates is involved
      in visual processes. Consequently, the loss of vision, either at birth or later
      in life, affects brain organization and the way the world is perceived and acted
      upon. In this paper, we address a number of issues on the nature of consciousness
      in people deprived of vision. Do brains from sighted and blind individuals
      differ, and how? How does the brain of someone who has never had any visual
      perception form an image of the external world? What is the subjective correlate
      of activity in the visual cortex of a subject who has never seen in life? More in
      general, what can we learn about the functional development of the human brain in
      physiological conditions by studying blindness? We discuss findings from animal
      research as well from recent psychophysical and functional brain imaging studies
      in sighted and blind individuals that shed some new light on the answers to these
      questions.

PMID- 21713180
TI  - Gender affects body language reading.
AB  - Body motion is a rich source of information for social cognition. However, gender
      effects in body language reading are largely unknown. Here we investigated
      whether, and, if so, how recognition of emotional expressions revealed by body
      motion is gender dependent. To this end, females and males were presented with
      point-light displays portraying knocking at a door performed with different
      emotional expressions. The findings show that gender affects accuracy rather than
      speed of body language reading. This effect, however, is modulated by emotional
      content of actions: males surpass in recognition accuracy of happy actions,
      whereas females tend to excel in recognition of hostile angry knocking. Advantage
      of women in recognition accuracy of neutral actions suggests that females are
      better tuned to the lack of emotional content in body actions. The study provides
      novel insights into understanding of gender effects in body language reading, and
      helps to shed light on gender vulnerability to neuropsychiatric and
      neurodevelopmental impairments in visual social cognition.

PMID- 21713181
TI  - Frequency specific modulation of human somatosensory cortex.
AB  - Oscillatory neuronal activities are commonly observed in response to sensory
      stimulation. However, their functional roles are still the subject of debate. One
      way to probe the roles of oscillatory neural activities is to deliver alternating
      current to the cortex at biologically relevant frequencies and examine whether
      such stimulation influences perception and cognition. In this study, we tested
      whether transcranial alternating current stimulation (tACS) over the primary
      somatosensory cortex (SI) could elicit tactile sensations in humans in a
      frequency-dependent manner. We tested the effectiveness of tACS over SI at
      frequency bands ranging from 2 to 70 Hz. Our results show that stimulation in
      alpha (10-14 Hz) and high gamma (52-70 Hz) frequency range produces a tactile
      sensation in the contralateral hand. A weaker effect was also observed for beta
      (16-20 Hz) stimulation. These findings highlight the frequency dependency of
      effective tACS over SI with the effective frequencies corresponding to those
      observed in previous electroencephalography/magnetoencephalography studies of
      tactile perception. Our present study suggests that tACS could be used as a
      powerful online stimulation technique to reveal the causal roles of oscillatory
      brain activities.

PMID- 21713182
TI  - Quiet eye training facilitates competitive putting performance in elite golfers.
AB  - The aim of this study was to examine the effectiveness of a brief quiet eye (QE)
      training intervention aimed at optimizing visuomotor control and putting
      performance of elite golfers under pressure, and in real competition. Twenty-two
      elite golfers (mean handicap 2.7) recorded putting statistics over 10 rounds of
      competitive golf before attending training individually. Having been randomly
      assigned to either a QE training or Control group, participants were fitted with
      an Applied Science Laboratories Mobile Eye tracker and performed 20 baseline (pre
      test) putts from 10 ft. Training consisted of video feedback of their gaze
      behavior while they completed 20 putts; however the QE-trained group received
      additional instructions related to maintaining a longer QE period. Participants
      then recorded their putting statistics over a further 10 competitive rounds and
      re-visited the laboratory for retention and pressure tests of their visuomotor
      control and putting performance. Overall, the results were supportive of the
      efficacy of the QE training intervention. QE duration predicted 43% of the
      variance in putting performance, underlying its critical role in the visuomotor
      control of putting. The QE-trained group maintained their optimal QE under
      pressure conditions, whereas the Control group experienced reductions in QE when
      anxious, with subsequent effects on performance. Although their performance was
      similar in the pre-test, the QE-trained group holed more putts and left the ball
      closer to the hole on missed putts than their Control group counterparts in the
      pressure test. Importantly, these advantages transferred to the golf course,
      where QE-trained golfers made 1.9 fewer putts per round, compared to pre
      training, whereas the Control group showed no change in their putting statistics.
      These results reveal that QE training, incorporated into a pre-shot routine, is
      an effective intervention to help golfers maintain control when anxious.

PMID- 21713183
TI  - Competition for cognitive resources during rapid serial processing: changes
      across childhood.
AB  - The ability to direct cognitive resources to target objects despite distraction
      by competing information plays an important role for the development of mental
      aptitudes and skills. We examined developmental changes of this ability in a
      cross-sectional design, using the "attentional blink" (AB) paradigm. The AB is a
      pronounced impairment of T2 report, which occurs when a first (T1) and second
      target (T2) embedded in a rapid stimulus sequence are separated by at least one
      distractor and occur within 500 ms of each other. Two groups of children (6- to 7
      year-olds and 10- to 11-year-olds; ns = 21 and 24, respectively) were asked to
      identify green targets in two AB tasks: one using non-linguistic symbols and the
      other letters or words. The temporal distance or stimulus-onset asynchrony (SOA)
      between T1 and T2 varied between no intervening distractor (Lag 1, 116-ms SOA)
      and up to 7 intervening distractors (Lag 8, 928-ms SOA). In the symbol task,
      younger children linearly increased T2 identification with increasing lag. Older
      children, however, displayed a hook-shaped pattern as typically seen in adults,
      with lowest identification reports in T2 symbols at the critical blink interval
      (Lag 2, 232-ms SOA), and a slight performance gain for the Lag 1 condition. In
      the verbal task, the older group again exhibited a prominent drop in T2
      identification at Lag 2, whereas the younger group showed a more alleviated and
      temporally diffuse AB impairment. Taken together, this pattern of results
      suggests that the control of attention allocation and/or working memory
      consolidation of targets among distractors represents a cognitive skill that
      emerges during primary school age.

PMID- 21713185
TI  - Interactive graphics: exemplified with real data applications.
AB  - Graphics are widely used in modern applied statistics because they are easy to
      create, convenient to use, and they can present information effectively. Static
      plots do not allow interacting with graphics. User interaction, on the other
      hand, is crucial in exploring data. It gives flexibility and control. One can
      experiment with the data and the displays. One can investigate the data from
      different perspectives to produce views that are easily interpretable and
      informative. In this paper, we try to explain interactive graphics and advocate
      their use as a practical tool. The benefits and strengths of interactive graphics
      for data exploration and data quality analyses are illustrated systematically
      with three complex real datasets.

PMID- 21713184
TI  - The mechanics of embodiment: a dialog on embodiment and computational modeling.
AB  - Embodied theories are increasingly challenging traditional views of cognition by
      arguing that conceptual representations that constitute our knowledge are
      grounded in sensory and motor experiences, and processed at this sensorimotor
      level, rather than being represented and processed abstractly in an amodal
      conceptual system. Given the established empirical foundation, and the relatively
      underspecified theories to date, many researchers are extremely interested in
      embodied cognition but are clamoring for more mechanistic implementations. What
      is needed at this stage is a push toward explicit computational models that
      implement sensorimotor grounding as intrinsic to cognitive processes. In this
      article, six authors from varying backgrounds and approaches address issues
      concerning the construction of embodied computational models, and illustrate what
      they view as the critical current and next steps toward mechanistic theories of
      embodiment. The first part has the form of a dialog between two fictional
      characters: Ernest, the "experimenter," and Mary, the "computational modeler."
      The dialog consists of an interactive sequence of questions, requests for
      clarification, challenges, and (tentative) answers, and touches the most
      important aspects of grounded theories that should inform computational modeling
      and, conversely, the impact that computational modeling could have on embodied
      theories. The second part of the article discusses the most important open
      challenges for embodied computational modeling.

PMID- 21713186
TI  - Reorganization of the injured brain: implications for studies of the neural
      substrate of cognition.
AB  - In the search for a neural substrate of cognitive processes, a frequently
      utilized method is the scrutiny of post-traumatic symptoms exhibited by
      individuals suffering focal injury to the brain. For instance, the presence or
      absence of conscious awareness within a particular domain may, combined with
      knowledge of which regions of the brain have been injured, provide important data
      in the search for neural correlates of consciousness. Like all studies addressing
      the consequences of brain injury, however, such research has to face the fact
      that in most cases, post-traumatic impairments are accompanied by a "functional
      recovery" during which symptoms are reduced or eliminated. The apparent
      contradiction between localization and recovery, respectively, of functions
      constitutes a problem to almost all aspects of cognitive neuroscience. Several
      lines of investigation indicate that although the brain remains highly plastic
      throughout life, the post-traumatic plasticity does not recreate a copy of the
      neural mechanisms lost to injury. Instead, the uninjured parts of the brain are
      functionally reorganized in a manner which - in spite of not recreating the basic
      information processing lost to injury - is able to allow a more or less complete
      return of the surface phenomena (including manifestations of consciousness)
      originally impaired by the trauma. A novel model [the Reorganization of
      Elementary Functions-model] of these processes is presented - and some of its
      implications discussed relative to studies of the neural substrates of cognition
      and consciousness.

PMID- 21713187
TI  - What does Neural Plasticity Tell us about Role of Primary Visual Cortex (V1) in
      Visual Awareness?
AB  - The complete loss of visual awareness resulting from a lesion to the primary
      visual cortex (V1) suggests that this region is indispensable for conscious
      visual perception. There are however a number cases of conscious perception in
      the absence of V1 which appear to challenge this conclusion. These include
      reports of patients with bilateral V1 lesions sustained at an early age whose
      conscious vision has spontaneously recovered, as well as stroke patients who have
      recovered some conscious vision with the help of rehabilitation programs. In
      addition, the phenomenon of hemianopic completion and percepts induced by brain
      stimulation suggest that V1 may not be necessary for conscious perception in all
      circumstances. Furthermore, that the visual abilities in the cat are associated
      with the recovery of normal extrastriate tuning properties rather than emulation
      of V1 functions suggests that there is nothing unique about the functional
      properties of this region in visual awareness. Rather, the dramatic effect of a
      V1 lesion on visual awareness may be due to its role in providing the majority of
      extrastriate visual input, the loss of which abolishes normal neural
      responsiveness throughout the visual cortex.

PMID- 21713188
TI  - The grammar of exchange: a comparative study of reciprocal constructions across
      languages.
AB  - Cultures are built on social exchange. Most languages have dedicated grammatical
      machinery for expressing this. To demonstrate that statistical methods can also
      be applied to grammatical meaning, we here ask whether the underlying meanings of
      these grammatical constructions are based on shared common concepts. To explore
      this, we designed video stimuli of reciprocated actions (e.g., "giving to each
      other") and symmetrical states (e.g., "sitting next to each other"), and with the
      help of a team of linguists collected responses from 20 languages around the
      world. Statistical analyses revealed that many languages do, in fact, share a
      common conceptual core for reciprocal meanings but that this is not a universally
      expressed concept. The recurrent pattern of conceptual packaging found across
      languages is compatible with the view that there is a shared non-linguistic
      understanding of reciprocation. But, nevertheless, there are considerable
      differences between languages in the exact extensional patterns, highlighting
      that even in the domain of grammar semantics is highly language-specific.

PMID- 21713189
TI  - Neural mechanisms of anaphoric reference revealed by FMRI.
AB  - Pronouns are bound to their antecedents by matching syntactic and semantic
      information. The aim of this functional magnetic resonance imaging study was to
      localize syntactic and semantic information retrieval and integration during
      pronoun resolution. Especially we investigated their possible interaction with
      verbal working memory manipulated by distance between antecedent and pronoun. We
      disentangled biological and syntactic gender information using German sentences
      about persons (biological/syntactic gender) or things (syntactic gender) followed
      by congruent or incongruent pronouns. Increasing the distance between pronoun and
      antecedent resulted in a short and a long distance condition. Analysis revealed a
      language related network including inferior frontal regions bilaterally
      (integration), left anterior and posterior temporal regions (lexico-semantics and
      syntactic retrieval) and the anterior cingulate gyrus (conflict resolution)
      involved in pronoun resolution. Activities within the inferior frontal region
      were driven by Congruency (incongruent > congruent) and Distance (long > short).
      Temporal regions were sensitive to Distance and Congruency (but solely within
      long distant conditions). Furthermore, anterior temporal regions were sensitive
      to the antecedent type with an increased activity for person pronouns compared to
      thing pronouns. We suggest that activity modulations within these areas reflect
      the integration process of an appropriate antecedent which depends on the type of
      information that has to be retrieved (lexico-syntactic posterior temporal, lexico
      semantics anterior temporal). It also depends on the overall syntactic and
      semantic complexity of long distant sentences. The results are interpreted in the
      context of the memory-unification-control model for sentence comprehension as
      proposed by Vosse and Kempen (2000), Hagoort (2005), and Snijders et al. (2009).

PMID- 21713190
TI  - Single-trial regression elucidates the role of prefrontal theta oscillations in
      response conflict.
AB  - In most cognitive neuroscience experiments there are many behavioral and
      experimental dynamics, and many indices of brain activity, that vary from trial
      to trial. For example, in studies of response conflict, conflict is usually
      treated as a binary variable (i.e., response conflict exists or does not in any
      given trial), whereas some evidence and intuition suggests that conflict may vary
      in intensity from trial to trial. Here we demonstrate that single-trial multiple
      regression of time-frequency electrophysiological activity reveals neural
      mechanisms of cognitive control that are not apparent in cross-trial averages. We
      also introduce a novel extension to oscillation phase coherence and
      synchronization analyses, based on "weighted" phase modulation, that has
      advantages over standard coherence measures in terms of linking
      electrophysiological dynamics to trial-varying behavior and experimental
      variables. After replicating previous response conflict findings using trial
      averaged data, we extend these findings using single-trial analytic methods to
      provide novel evidence for the role of medial frontal-lateral prefrontal theta
      band synchronization in conflict-induced response time dynamics, including a role
      for lateral prefrontal theta-band activity in biasing response times according to
      perceptual conflict. Given that these methods shed new light on the prefrontal
      mechanisms of response conflict, they are also likely to be useful for
      investigating other neurocognitive processes.

PMID- 21713191
TI  - Assessing the usefulness of google books' word frequencies for psycholinguistic
      research on word processing.
AB  - In this Perspective Article we assess the usefulness of Google's new word
      frequencies for word recognition research (lexical decision and word naming). We
      find that, despite the massive corpus on which the Google estimates are based
      (131 billion words from books published in the United States alone), the Google
      American English frequencies explain 11% less of the variance in the lexical
      decision times from the English Lexicon Project (Balota et al., 2007) than the
      SUBTLEX-US word frequencies, based on a corpus of 51 million words from film and
      television subtitles. Further analyses indicate that word frequencies derived
      from recent books (published after 2000) are better predictors of word processing
      times than frequencies based on the full corpus, and that word frequencies based
      on fiction books predict word processing times better than word frequencies based
      on the full corpus. The most predictive word frequencies from Google still do not
      explain more of the variance in word recognition times of undergraduate students
      and old adults than the subtitle-based word frequencies.

PMID- 21713193
TI  - Second opinion in plastic surgery.

PMID- 21713192
TI  - Succumbing to bottom-up biases on task choice predicts increased switch costs in
      the voluntary task switching paradigm.
AB  - Bottom-up biases are widely thought to influence task choice in the voluntary
      task switching paradigm. Definitive support for this hypothesis is lacking,
      however, because task choice and task performance are usually confounded. We
      therefore revisited this hypothesis using a paradigm in which task choice and
      task performance are temporally separated. As predicted, participants tended to
      choose the task that was primed by bottom-up biases. Moreover, such choices were
      linked to increased switch costs during subsequent task performance. These
      findings provide compelling evidence that bottom-up biases influence voluntary
      task choice. They also suggest that succumbing to such biases reflects a
      reduction of top-down control that persists to influence upcoming task
      performance.

PMID- 21713194
TI  - Is chronic venous ulcer curable? A sample survey of a plastic surgeon.
AB  - INTRODUCTION: Venous ulcers of lower limbs are often chronic and non-healing,
      many a time neglected by patients and their treating physicians as these ulcers
      mostly do not lead to amputation as in gangrenous arterial ulcer and also cost
      much to complete the course of treatment and prevention of recurrence. MATERIALS
      AND METHODS: One hundred and twenty two lower limb venous ulcers came up for
      treatment between May 2006 and April 2009. Only twenty nine cases completed the
      treatment. The main tool of investigation was the non invasive Duplex scan
      venography. Biopsy of the ulcer was done for staging the disease. Patients'
      choice of treatment was always conservative and as out-patient instead of
      hospitalisation and surgery, which required a lot of motivation by the treating
      unit. RESULTS: Out of twenty nine cases, ten cases were treated conservatively
      and seven (24.13%) healed well. Remaining nineteen cases were given surgical
      modality in which fifteen cases (51.74%) were successful. Only seven cases
      (24.13%) failed to heal. Compression stockings were advised to control oedema,
      varices and pain. Foot care, regular exercises and follow-up were stressed
      effectively.

PMID- 21713195
TI  - Venous ulcer: Current concepts.

PMID- 21713196
TI  - Evaluations of bacterial contaminated full thickness burn wound healing in
      Sprague Dawley rats Treated with Tualang honey.
AB  - AIM: The effect of Tualang honey on wound healing in bacterial contaminated full
      thickness burn wounds was evaluated in 36 male Sprague Dawley rats. MATERIALS AND
      METHODS: The rats were randomly divided into three groups (n = 12/group). Three
      full-thickness burn wounds were created on each rat. Each group of rats was
      inoculated with a different organism in the burn wounds: Group A was inoculated
      with Pseudomonas aeruginosa, Group B was inoculated with Klebsiella pneumoniae
      and Group C was inoculated with Acinetobacter baumannii. One wound on each rat
      was dressed with either Tualang honey, Chitosan gel or Hydrofibre silver. Each
      wound size was measured on day 3, 6, 9, 12, 15, 18 and 21 of the study. RESULTS:
      The mean wound size of the Tualang honey-treated wounds was not statistically
      different than that of the Chitosan gel or Hydrofibre silver-treated wounds when
      the wounds were compared throughout the entire experiment (P > 0.05). However,
      comparing the mean wound size on day 21 alone revealed that the Tualang honey
      treated wounds were smaller in comparison to that of the Chitosan gel and
      Hydrofibre silver-treated groups. CONCLUSIONS: This study shows that topical
      application of Tualang honey on burn wounds contaminated with P. aeruginosa and
      A. baumannii gave the fastest rate of healing compared with other treatments.

PMID- 21713197
TI  - Soluble CD163: A novel biomarker for the susceptibility to sepsis in severe burn
      injuries.
AB  - OBJECTIVE: Soluble CD163 (sCD163) has been previously shown to play a role in
      inflammatory and infectious diseases. This study, for the first time,
      investigates the characteristics and potential values of sCD163 in burn patients.
      A first look is taken on the changes of sCD163 levels in burn patients by
      comparing predefined subgroups at single time points. MATERIALS AND METHODS:
      Serum samples of 18 patients with burn injuries were collected for biochemical
      analysis at the time of admission and in a chronological sequence of 12, 24, 48
      and 120 h after the injury and were matched to clinical parameters. Statistical
      analysis was performed using the Mann-Whitney test, Wilcoxon signed rank and
      Pearson bivariate correlation. RESULTS: Patients with sepsis showed a significant
      increase of sCD163 levels. sCD163 was correlated with leukocytes (P=0.035) over
      the time course of 120 h. Patients characterized by a burn size exceeding 25% of
      the total body surface area (TBSA) showed a significant increase of sCD163
      between 12 and 48 h after burn injury (P=0.038). CONCLUSIONS: The first view on
      the characteristics of sCD163 in the serum of burn patients points out that
      sCD163 seems to be an early indicator for the susceptibility to sepsis.
      Furthermore, the changes in sCD163 serum levels within the first hours after burn
      trauma have great potential for early prediction of organ failure after burn
      injury.

PMID- 21713198
TI  - Soluble CD 163: A novel biomarker.

PMID- 21713199
TI  - Histomorphometric and sympathetic innervation of the human superficial temporal
      artery.
AB  - CONTEXT: Following microvascular surgeries, stenosis and spasm of the arterial
      graft or the recipient vessel are serious complications which are often caused by
      intimal hyperplasia and perivascular nerves, respectively. AIMS: The purpose of
      this study was to understand the characteristics of arterial wall and sympathetic
      innervation of the human superficial temporal artery (STA) and also, the effect
      of aging on STA. METHODS AND MATERIALS: Fifty-two fresh human STA (frontal
      branch) samples were obtained from 26 cadavers (19 males and 7 females) between
      the ages of 19 and 83 years. Samples were divided into three age groups: G1, 19
      40 years; G2, 41-60 years; G3, over 61 years. 5MUm-thin sections of each sample
      were taken and stained with haematoxylin-eosin, Verhoff's and tyrosine
      hydroxylase (TH) immunostaining. RESULTS: The well-defined internal elastic
      lamina (IEL) was observed in all samples of STA, whereas external elastic lamina
      (EEL) was not prominent in almost all cases or absent in few cases. This might be
      the important factor in the process of intimal and medial hyperplasia in the
      frontal branch of STA. Notably, intimal thickening appeared from second decade of
      life. Sympathetic fibres are located mainly in tunica adventitia and outer media.
      Mean adventitial and sympathetic areas were found to be 0.080 and 0.010mm(2),
      respectively. STATISTICAL ANALYSIS USED: One-way ANOVA followed by Tukey HSD post
      hoc test by using the SPSS 11.5 software. CONCLUSIONS: STA is prone to age
      related pathological changes. Sympathetic index may be used for analysis of
      sympathetic fibre-related problems (vasospasm, migraine) of the STA.

PMID- 21713200
TI  - Incidence of agenesis of palmaris longus in the Andhra population of India.
AB  - BACKGROUND: The knowledge of Palmaris longus (PL) is a growing interest for its
      wide role in reconstructive plastic surgeries as a donor tendon for transfer or
      transplant. The prevalence of the PL agenesis has been well-documented by many
      authors in different ethnic groups or populations. Many conventional tests for
      determining the presence of the PL has been described, but lamentably there are
      many discrepancies in confirming its presence or absence. Slight modifications of
      the prevailing methods can still give authenticate results. AIM: This prospective
      study was conducted to determine the incidence of unilateral and bilateral
      agenesis of PL and its association with sex and side of the limb in the Andhra
      population of India. MATERIALS AND METHODS: A total of 942 subjects of both sexes
      belonging to 18-23 years were used to access the PL using various tendon
      examination techniques including our modified Schaeffer's test. The data
      collected were analyzed by Pearsons chi(2) test using SPSS software. RESULTS:
      Overall agenesis of muscle in both sexes was 264 (28.0%), out of which 40.2% was
      seen in females and 14.7% in males with the ratio of 3:1. The unilateral agenesis
      was seen in 70.5% and bilateral agenesis in 29.5% subjects. The left side
      agenesis was seen in 51.6% and right side in 48.4% subjects. CONCLUSIONS: The
      prevalence of bilateral and unilateral agenesis was more common on left side with
      a greater likelihood in the female subjects. The proposed technique could bring
      better results in all subjects and can be implemented in manual examination of
      PL.

PMID- 21713201
TI  - Congenital pseudoarthrosis of the tibia with localised gigantism in a case of
      congenital constriction band syndrome.

PMID- 21713202
TI  - Body contouring following massive weight loss.
AB  - Obesity is a global disease with epidemic proportions. Bariatric surgery or
      modified lifestyles go a long way in mitigating the vast weight gain. Patients
      following these interventions usually undergo massive weight loss. This results
      in redundant tissues in various parts of the body. Loose skin causes increased
      morbidity and psychological trauma. This demands various body contouring
      procedures that are usually excisional. These procedures are complex and part of
      a painstaking process that needs a committed patient and an industrious plastic
      surgeon. As complications in these patients can be quite frequent, both the
      patient and the surgeon need to be aware and willing to deal with them.

PMID- 21713203
TI  - A multi-staged approach to the reconstruction of a burnt Asian face.
AB  - This article describes the management of chemical burns to the Asian face with
      resultant full thickness loss to the right side of the face including the eyelid
      and nose. We detail the techniques used to reconstruct the face which include
      skin grafting according to the aesthetic units of the face, accurate placement of
      junction lines, use of a chondrocutaneous graft to reconstruct the alar grove and
      scalp strip grafting for eyebrow reconstruction. We obtained a successful result
      that minimised scar formation in the burnt Asian face.

PMID- 21713204
TI  - Ascher syndrome: Review of literature and case report.
AB  - A 13 year old girl presented with aesthetic deformity of upper lip since birth.
      She also presented with eyelid swelling on and off for 11 months. She was
      diagnosed to be a rare case of Ascher syndrome. Ascher syndrome commonly presents
      with double lip and blepharochalasis, sometimes associated with goitre. The
      deformity of her double upper lip was corrected by appropriate surgery. Because
      her blepharochalasis is in active stage now, she is under periodic follow up for
      appropriate intervention. This article describes the management of the patient
      and brief overview of the syndrome. Ascher syndrome is often missed or
      misdiagnosed commonly.

PMID- 21713205
TI  - Salvage of foot with extensive giant cell tumour with transfer of vascularised
      fibular bone graft.
AB  - Though giant cell tumor is not uncommon in young adults, simultaneous involvement
      of multiple mid-foot bones is very uncommon and very difficult to treat. For
      reconstruction of large segmental bony defects following tumour excision, free
      vascularized bone graft is an excellent surgical option. We report a case with
      extensive involvement of all the tarsal bones and metatarsal bases in a young
      adult. After excision his foot was reconstructed with vascularised bone flap. We
      were able to save his foot after a wide local excision and reconstruction with
      free fibula graft. Graft united early and showed excellent remodelling because of
      good vascularity. We feel that this method deserves consideration as a last
      attempt to salvage functional foot in disease like this.

PMID- 21713206
TI  - Understanding the fibula by the candle model.

PMID- 21713207
TI  - Understanding the fibula by the candle model.

PMID- 21713208
TI  - The use of bone wax for protection from sharp ends of interdental wires.

PMID- 21713209
TI  - Modified right-angled forceps for Gigli's wire saw retrieval during osteotomy.

PMID- 21713210
TI  - The ulnar digital artery perforator flap.

PMID- 21713211
TI  - The Sommerlad pen: Yet another use.

PMID- 21713212
TI  - Clinical outcome of shoulder muscle transfer for shoulder deformities in
      obstetric brachial plexus palsy: A study of 150 cases.
AB  - BACKGROUND: Residual muscle weakness, cross-innervation (caused by misdirected
      regenerating axons), and muscular imbalance are the main causes of internal
      rotation contractures leading to limitation of shoulder joint movement, glenoid
      dysplasia, and deformity in obstetric brachial plexus palsy. Muscle transfers and
      release of antagonistic muscles improve range of motion as well as halt or
      reverse the deterioration in the bony architecture of the shoulder joint. The aim
      of our study was to evaluate the clinical outcome of shoulder muscle transfer for
      shoulder abnormalities in obstetric brachial plexus palsy. MATERIALS AND METHODS:
      One hundred and fifty patients of obstetric brachial plexus palsy with shoulder
      deformity underwent shoulder muscle transfer along with anterior shoulder release
      at our institutions from 1999 to 2007. Shoulder function was assessed both
      preoperatively and postoperatively using aggregate modified Mallet score and
      active and passive range of motion. The mean duration of follow-up was 4 years
      (2.5-8 years). RESULTS: The mean preoperative abduction was 45 degrees  +/- 7.12,
      mean passive external rotation was 10 degrees  +/- 6.79, the mean active external
      rotation was 0 degrees , and the mean aggregate modified Mallet score was 11.2 +/
      1.41. At a mean follow-up of 4 years (2.5-8 years), the mean active abduction
      was 120 degrees  +/- 18.01, the mean passive external rotation was 80 degrees  +/
      10.26, while the mean active external rotation was 45 degrees  +/- 3.84. The
      mean aggregate modified Mallet score was 19.2 +/- 1.66. CONCLUSIONS: This
      procedure can thus be seen as a very effective tool to treat internal rotation
      and adduction contractures, achieve functional active abduction and external
      rotation, as well as possibly prevent glenohumeral dysplasia, though the long
      term effects of this procedure may still have to be studied in detail clinico
      radiologically to confirm this hypothesis. LEVEL OF EVIDENCE: Therapeutic level
      IV.

PMID- 21713213
TI  - Spectrum of primary bone grafting in cranio maxillofacial trauma at a tertiary
      care centre in India.
AB  - BACKGROUND: In past several years, traumas following road traffic accidents and
      other causes have increased, owing to an increase in mechanization and pace of
      life. These patients frequently have complicated injuries involving soft tissue
      and the craniofacial skeleton. Assessment of bony injuries and loss of portions
      of facial skeleton and their management has proved to be a challenge to the
      reconstructive surgeon. AIMS: Primary bone grafting of craniofacial skeletal
      injuries provides an opportunity for one stage correction of bony defects. The
      varied spectrum of primary bone grafts for management of craniomaxillofacial
      injuries are evaluated in this study. MATERIALS AND METHODS: Patients with a
      history of acute trauma resulting in facial skeletal injuries with or without
      bone loss were included in the study. Primary bone grafting was undertaken in
      situations requiring contour correction, replacement of skeletal losses and for
      rigid fixation of fracture segments. Olecranon, Iliac crest, ribs, Vascularized
      as well as nonvascularized outer table calvarial grafts and nonvascularized inner
      table calvarial grafts were used in this study. RESULTS: Sixty two patients of
      craniomaxillofacial injury following trauma requiring primary bone grafting were
      considered in this study. Fifty seven percent of patients (n=32) required primary
      bone grafting for replacement of bone loss while bone grafting for contour
      correction was done in twenty three patients. The parietal calvaria overlying the
      non-dominant hemisphere was used as a source of bone graft in forty-nine
      patients. Nearly ninety-two percent of the patients were satisfied with the
      results of primary bone grafting. CONCLUSIONS: Functional and aesthetic
      assessment of each of these patients, managed with primary bone grafting revealed
      a low rate of disabilities and high percentage of satisfaction in this study.

PMID- 21713214
TI  - Pour water on burns - prof. M.h. Keswani.

PMID- 21713215
TI  - Radial bone graft usage for nasal septal reconstruction.
AB  - BACKGROUND: Although various techniques have been described for correction of
      crooked and saddle nose deformities, these problems are challenging with high
      recurrence and revision rates. Conventional septal surgery may not be adequate
      for nose reconstruction in crooked and saddle nose deformities. MATERIALS AND
      METHODS: Between December 2005 and October 2009, six patients with crooked nose
      and five patients with saddle nose deformities underwent corrective surgery in
      our clinic. All patients were male, and the mean age was 21 years (range, 19-23
      years). We used rigid radial bone graft to prevent redeviation and recurrence
      following corrective nasal septal surgery. RESULTS: The mean follow-up period was
      28 months, ranging from 18 to 46 months. Mean operation time was 4 hours (3-4.5).
      All patients healed uneventfully. None of the patients required secondary
      surgery. CONCLUSIONS: We believe that radial bone grafts offer a long lasting
      support in treatment of challenging cases with crooked and saddle nose
      deformities.

PMID- 21713216
TI  - Descriptive study of management of palatal fistula in one hundred and ninety-four
      cleft individuals.
AB  - OBJECTIVE: Palatal fistula is a significant complication following cleft palate
      repair. The guidelines of management of the palatal fistula is dependent on the
      type of cleft, site of fistula, condition of surrounding tissue and associated
      problem. We studied the management and outcome of 194 cleft palate fistula in our
      institute. DESIGN: We present the descriptive hospital-based study of management
      of palatal fistula in 194 cleft patients. We have excluded all the syndromic
      children and children whose anterior palate was not operated as per protocol.
      SETTINGS: Of 194 cleft palate fistula, 37 had palate repair in our hospital and
      157 were refereed with fistula following palate repair.The patients were
      evaluated by interdisciplinary team and plan of management was decided. RESULT:
      Various parameters like types of cleft, site of fistula and management of fistula
      were studied in all the patients. Fifty-two percent were in unilateral CLP and
      30% in bilateral CLP because unilateral CLP is the commonest type of cleft.
      Postalveolar and hard palate region contributing to 67% of all fistulae, followed
      by junctional in (9%). Seventy-two percent of fistula were amenable for repair by
      local available tissue, 28% needed tongue flap due to shortage of tissue. Minor
      numbers have failure of procedure for fistula closure needing further management.
      CONCLUSIONS: This descriptive study present analysis of management of fistula in
      our institute. It also reinforces that patient with bilateral cleft lip and
      palate more likely to have shortage of local tissue needing the local flaps like
      tongue flap compare to other cleft types. The surgical management of fistula can
      be combined to tackle the associated problems.

PMID- 21713217
TI  - Management of palatal fistulae.

PMID- 21713218
TI  - Evaluation of stressors and coping strategies for stress in Indian
      anaesthesiologists.
AB  - Several studies have been done to assess job satisfaction and quantify effects of
      stressors on anaesthesiologists in different regions and countries. Studies
      related to stress in Indian anaesthesiologists are very limited, which prompted
      us to design this study not only to identify the stressors but also to find out
      how anaesthesiologists react to stress and devise means to minimize it to
      increase their job satisfaction levels. A set of questions was handed over
      personally to 200 anaesthesiologists at the national- and state-level
      anaesthesiology conferences and continuing medical educations with a request to
      return them duly filled in, with an assurance that confidentiality and anonymity
      would bemaintained. Main outcome measures were demographics, factors causing
      stress, how the responding anaesthesiologists and their colleagues react to it
      and methods they adopt to reduce stress at their workplace. Response rate was
      96%. The total number of respondents was 192 (54% males and 46% females; juniors,
      76%; and seniors, 24%). Identified stressors were as follows: time constraints
      (34%), medicolegal concerns (24%), interference with home life (22%), clinical
      problems (20%) and communication problems (9%). Different strategies for coping
      with stress were identified. This survey is just a beginning. Indian Society of
      Anaesthesiologists is requested to look into the matter and take it further on a
      larger scale by multicentric studies to lay down standards related to number of
      working hours, number of night-call duties per week, proper assistance,
      medicolegal protection, etc., which would not only reduce occupational stress but
      also improve efficiency and job satisfaction among anaesthesiologists.

PMID- 21713219
TI  - Hyperthyroidism and jaundice.
AB  - Development of hyperbilirubinemia, concurrent or subsequent to hyperthyroidism,
      can be due to thyrotoxicosis per se, or due to drug treatment of hyperthyroidism.
      Other rare conditions: autoimmune thyroid disease, or causes unrelated to
      hyperthyroidism like viral hepatitis, alcohol abuse, sepsis, cholangitis, or as a
      side effect of certain medications. In this article, we review these causes of co
      existent hyperthyroidism and jaundice. We also highlight the changes to be
      expected while interpreting thyroid function tests vis-a-vis liver function tests
      in this subgroup of patients.

PMID- 21713220
TI  - Quantitative analysis of SPECT imaging parameters in patients with resting
      perfusion defects on myocardial perfusion scintigraphy.
AB  - BACKGROUND: Functional status/contractile behaviour of hibernating myocardium was
      analyzed objectively by analyzing the available quantitative parameters obtained
      on gated SPECT myocardial perfusion imaging (MPI) using Emory cardiac toolbox
      (ECTB) software. MATERIALS AND METHODS: In this retrospective study, 70 patients
      with perfusion defects on (99)Tc-Sestamibi MPI (12 females, 58 males) who also
      underwent (18)F-FDG Cardiac PET study for assessment of hibernating myocardium
      were included for analysis. Patients were divided in three categories based on
      summed rest score (SRS) obtained from ECTB software, depicting the extent of
      perfusion defects. In a study population matched for extent of perfusion defects,
      quantitative parameters obtained from ECTB software such as left ventricular
      ejection fraction (LVEF), left ventricular end diastolic volume (EDV), left
      ventricular end systolic volume (ESV) and left ventricular stroke volume (SV)
      were compared between patients showing evidence of hibernating myocardium and
      patients showing no evidence of hibernating myocardium. Student 't' test was
      applied on the given observations and a P-value <0.05 was considered as a
      significant difference between the means in two categories. RESULTS: There was no
      significant difference in LVEF, EDV, ESV and SV measurements between those who
      demonstrate hibernating myocardium and those who show no evidence of hibernating
      myocardium across all the categories of patients. Few trends were evident in the
      present study in LVEF, EDV and ESV measurements i.e., fall in mean LVEF with
      increasing SRS and rise in mean EDV and ESV with increasing SRS. CONCLUSIONS: The
      findings were consistent with the nature of hibernating myocardium i.e., non
      contractile and dysfunctional. The fall in the LVEF was suggestive of
      deteriorating myocardial function with increasing extent of perfusion defects.
      The increasing left ventricular EDV and ESV with increasing extent of perfusion
      defects was suggestive of rising incidence of gross morphological LV cavity
      dilatation or "Dilated ischemic cardiomyopathy" in these patients.

PMID- 21713221
TI  - Role of Tc99m sulfur colloid scintigraphy in differentiating non-cirrhotic portal
      fibrosis from cirrhosis liver.
AB  - BACKGROUND: Two most important causes of portal hypertension are cirrhosis of
      liver and non-cirrhotic portal fibrosis (NCPF). The purpose of this study was to
      assess the scintigraphic appearances of Tc99m sulfur colloid liver scan in
      differentiating liver cirrhosis from NCPF. MATERIALS AND METHODS: Retrospective
      analysis records of 146 patients (91 male and 55 female) with diffuse
      hepatocellular disease was done for liver size, liver uptake, spleen size, spleen
      uptake, colloid shift to bone marrow and lungs. METHODS: Retrospective analysis
      records of 146 patients (91 male and 55 female) with diffuse hepatocellular
      disease was done for liver size, liver uptake, spleen size, spleen uptake,
      colloid shift to bone marrow and lungs. RESULTS: Cirrhotic livers showed patchy
      and lower uptake than NCPF (59% vs. 20%, P-value 0.041). Spleen size was
      significantly increased in NCPF compared to cirrhosis (100% vs. 67%, P-value
      0.0137). Significant colloid shift to bone marrow was noted in cirrhosis (84% vs.
      7%, P-value<0.0001). CONCLUSION: Tc99m sulfur colloid liver scan is a non
      invasive procedure having a useful adjunctive role in clinical differentiation of
      cirrhosis from NCPF.

PMID- 21713222
TI  - Rare developmental abnormalities of thyroid gland, especially multiple ectopia: A
      review and our experience.
AB  - BACKGROUND: Developmental structural abnormalities of the thyroid gland are
      relatively rare. There are scanty reports of hemiagensis, dual and triple ectopia
      of the thyroid in the literature MATERIALS AND METHODS: We did a retrospective
      analysis of 236 patients referred to us for Tc-99m Pertechnetate thyroid scan
      over period of four months (May 2010 to Sept 2010). Twenty of these 236 patients
      aged less than 20 years found to have developmental abnormality of the thyroid
      gland on thyroid scan. Diagnosis was correlated with anatomical imaging (USG/CT
      scan), fine needle aspiration cytology (FNAC) and histopathology. RESULTS: Out of
      the 20 patients, 8 were diagnosed with thyroglossal cyst, 4 with ectopic thyroid
      gland, 4 with dual ectopia, two had agenesis of thyroid gland, one case each with
      hemiagenesis and triple ectopia. CONCLUSION: The study has emphasized the
      indispensable role of Tc-99m Pertechnetate thyroid scan in the evaluation of
      midline neck swellings of childhood and diagnosing developmental anomalies of
      thyroid gland.

PMID- 21713223
TI  - Role of positron emission tomography-computed tomography in staging and early
      chemotherapy response evaluation in children with neuroblastoma.
AB  - BACKGROUND: To evaluate the role of positron emission tomography-computed
      tomography (PET-CT) in staging and determining early treatment response to
      chemotherapy in children with neuroblastoma (NB) and its correlation with the
      final outcome. PATIENTS AND METHODS: Seventeen patients of NB with mean age of
      51.5 months (age range 2-132 months; 14 males, 3 females) underwent serial 18F
      flourodeoxygl ucose (FDG) PET-CT imaging. All 17 patients were for staging before
      any treatment. Twelve of 17 patients underwent I-131 meta-iodobezylguanidine
      (MIBG) scan and bone scan. MIBG uptake was seen in the primary lesion in 11/12
      patients. MIBG uptake in bones was seen in 3/12 patients. All bone lesions were
      concordant on MIBG and bone scan. Early response to chemotherapy was evaluated
      after two cycles using PET-CT. A 30% reduction in longest diameter was taken as
      cut-off value for response on CT based on the response evaluation criteria in
      solid tumors criteria. Response on PET-CT was assessed using percentage
      improvement in lesion to background SUV ratio, taking a value of 50% as cut-off.
      Final outcome based on follow-up ranging from 6 to 43 months (mean 18.8 months)
      served as reference. RESULTS: All 17 patients showed increased FDG uptake at the
      primary site. Seven of the 17 patients (41.2%) showed metastasis. Lymph nodes
      were the most common site of metastatic disease followed by bone, bone marrow,
      lung and meninges. For response evaluation, change in the size of the primary
      tumor was noted in 11/17 (64.7%) patients on CT. Treatment response was noted in
      12/17 patients (70.6%) on PET-CT. Eleven out of 17 (65%) patients showed response
      in both CT and PET-CT. Five out of 17 patients showed no response in both.
      Discordant findings on CT and PET were noted in one (5.9%) patient where PET
      showed response but no response was seen on CT. Two patients with initial
      response but with distant metastases expired during follow-up. CONCLUSION: PET-CT
      has potential in the initial staging of NB. PET-CT also appears to be a good
      modality for response assessment in patients with moderate and high FDG uptake on
      the baseline scan. However, no significant beneficial effect was seen in patients
      with low baseline FDG uptake.

PMID- 21713224
TI  - Do reconstruction filters really effect the volume and ejection fraction
      calculation with 99Tc-sestamibigated myocardial SPECT?
AB  - BACKGROUND: ECG -gated myocardial perfusion imaging is a sensitive test for
      diagnosis of ischemia as well as scarred myocardium. It provides additional
      information on global and regional myocardial contractile function. A number of
      methods are available to calculate left ventricular volumes and ejection
      fractions, which depends on various technical and patients specific factor.
      OBJECTIVE: This study was carried out to measure effect of reconstruction filter
      in calculations of left ventricularend diastolic volume (EDV) and end systolic
      volume (ESV) and left ventricular ejection fraction (LVEF) from 99mTc-sestamibi
      myocardial perfusion imaging. MATERIALS AND METHODS: 99mTc-sestamibi-gated SPECT
      myocardial perfusion imaging was performed in 90 patients. Studies were
      reconstructed with Butterworth and Metz filters. RESULTS: Mean ejection fraction
      with Butterworth and Metz filter are 64.3 and 64.2, respectively. Mean EDV is for
      Butterworth and Metz filters are 77.3 and 78.5 ml, respectively. While ESV was
      36.49 and 36.63 ml, stroke volume calculated was 41.54 and 42 ml for Butterworth
      and Metz filters, respectively. Pearsons's correlation coefficients between
      results calculated with Metz and Butterworth filters were 0.994 for ESV, 0.996
      for EDV, 0.966 for LVEF and 0.925 for SV. Student 't' test was applied on the
      data and no significant difference was noted between parameter estimated by
      Butterworth or Metz filter. CONCLUSION: This study shows that difference of
      filter application has no significant effect in computing left ventricular
      function parameters.

PMID- 21713225
TI  - Choroidal metastasis from carcinoma of breast detected on F18-FDG PET CT scan: A
      case report and review of literature.
AB  - Intraocular choroidal metastasis is a very rare cause of blindness. Choroidal
      hemangioma and melanoma are other causes that may mimic the condition. Carcinoma
      of breast is the most common primary malignancy that accounts for choroidal
      metastasis in females and carcinoma of lung is the most common cause in males.
      Other primary neoplasms which can uncommonly metastasize to the choroid are
      testis, gastrointestinal tract, kidney, thyroid, pancreas, and prostate.
      Metastatic neoplasm to the eye outnumbers the primary tumors such as
      retinoblastomas and malignant melanoma. Sonography is usually the initial
      investigation after fundus examination to look for the architecture of the
      lesion. However, it lacks in specificity. We present a case of carcinoma of
      breast that had visual disturbances and wholebody F18-fluorodeoxyglucose,
      positron emission tomography-computerized tomography (FDG PET CT) revealed a
      choroidal lesion in addition to cerebral, pulmonary, and skeletal metastases.
      Choroidal metastasis from carcinoma of lung has been reported previously on FDG
      PET. To the best of our knowledge, this is the first case report of carcinoma of
      breast demonstrating choroid metastasis on F18-FDG PET CT scan.

PMID- 21713226
TI  - Tc 99m bone scan and fluorodeoxyglucose positron emission tomography in
      evaluation of disseminated langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder in which
      pathological langerhans cells accumulate in a variety of organs. Manifestations
      may include lung infiltrates, lymph node involvements, bone lesions, hepatic,
      hematopoietic and endocrine dysfunctions. In this case report we present fluorine
      18 positron emission tomography (F-18 PET/CT) and bone scintigraphy findings of a
      18-year-old male patient with disseminated LCH, mimicking multiple hypermetabolic
      metastatic lesions. Clinicians should be aware that LCH infiltrations can be seen
      as intense uptake and to differentiate infiltrations from other metastatic
      intense uptake with fluorodeoxyglucose PET/CT and bone scintigraphy, clinical and
      laboratory findings should be kept in mind.

PMID- 21713227
TI  - Functional movement screen normative values in a young, active population.
AB  - BACKGROUND: The Functional Movement Screen(TM) (FMS(TM)) is a screening
      instrument which evaluates selective fundamental movement patterns to determine
      potential injury risk. However, despite its global use, there are currently no
      normative values available for the FMS(TM). OBJECTIVES: To establish normative
      values for the FMS(TM) in a population of active, healthy individuals. Secondary
      aims were to investigate whether performance differed between males and females,
      between those with and without a previous history of injury, and to establish
      real-time inter-rater reliability of the FMS(TM). METHODS: Two hundred and nine
      (108 females and 101 males) physically active individuals, aged between 18 and 40
      years, with no recent (<6 weeks) history of musculoskeletal injury were
      recruited. All participants performed the FMS(TM) and were scored using the
      previously established standardized FMS(TM) criteria. A representative sub-group
      participant sample (28%) determined inter rater reliability. RESULTS: The mean
      composite FMS(TM) score was 15.7 with a 95% confidence interval between 15.4 and
      15.9 out of a possible total of 21. There was no statistically significant
      difference in scores between females and males (t(207) = .979, p = .329), or
      those who reported a previous injury and those who did not (t(207) = .688, p=
      .492). Inter-rater reliability (ICC(3,1)) for the composite FMS(TM) score was
      .971, demonstrating excellent reliability. Inter-rater reliability (Kappa) for
      individual test components of the FMS(TM) demonstrated substantial to excellent
      agreement (0.70 - 1.0). DISCUSSION AND CONCLUSION: This cross-sectional study
      provides FMS(TM) reference values for young, active individuals, which will
      assist in the interpretation of individual scores when screening athletes for
      musculoskeletal injury and performance factors.

PMID- 21713228
TI  - A pilot study of core stability and athletic performance: is there a
      relationship?
AB  - STUDY DESIGN: Correlation study OBJECTIVES: To objectively evaluate the
      relationship between core stability and athletic performance measures in male and
      female collegiate athletes. BACKGROUND: The relationship between core stability
      and athletic performance has yet to be quantified in the available literature.
      The current literature does not demonstrate whether or not core strength relates
      to functional performance. Questions remain regarding the most important
      components of core stability, the role of sport specificity, and the measurement
      of core stability in relation to athletic performance. METHODS: A sample of 35
      volunteer student athletes from Asbury College (NAIA Division II) provided
      informed consent. Participants performed a series of five tests: double leg
      lowering (core stability test), the forty yard dash, the T-test, vertical jump,
      and a medicine ball throw. Participants performed three trials of each test in a
      randomized order. RESULTS: Correlations between the core stability test and each
      of the other four performance tests were determined using a General Linear Model.
      Medicine ball throw negatively correlated to the core stability test (r -0.389,
      p=0.023). Participants that performed better on the core stability test had a
      stronger negative correlation to the medicine ball throw (r =-0.527). Gender was
      the most strongly correlated variable to core strength, males with a mean
      measurement of double leg lowering of 47.43 degrees compared to females having a
      mean of 54.75 degrees. CONCLUSIONS: There appears to be a link between a core
      stability test and athletic performance tests; however, more research is needed
      to provide a definitive answer on the nature of this relationship. Ideally,
      specific performance tests will be able to better define and to examine
      relationships to core stability. Future studies should also seek to determine if
      there are specific sub-categories of core stability which are most important to
      allow for optimal training and performance for individual sports.

PMID- 21713229
TI  - An update for the conservative management of patellofemoral pain syndrome: a
      systematic review of the literature from 2000 to 2010.
AB  - PURPOSE/BACKGROUND: Patellofemoral pain syndrome (PFPS) is one of the most common
      and clinically challenging knee pathologies. Historically, clinicians have used a
      myriad of interventions, many of which have benefited some but not all patients.
      Suboptimal outcomes may reflect the need for an evidence-based approach for the
      treatment of PFPS. The authors believe that integrating clinical expertise with
      the most current scientific data will enhance clinical practice. The purpose of
      this systematic review is to provide an update on the evidence for the
      conservative treatment of PFPS. METHODS: The PubMed, CINAHL, and SPORTDiscus
      databases were searched for studies published between January 1, 2000 and
      December 31, 2010. Studies used were any that utilized interventions lasting a
      minimum of 4 weeks for subjects with PFPS. Data were examined for subject sample,
      intervention duration, intervention type, and pain outcomes. RESULTS: General
      quadriceps strengthening continues to reduce pain in patients with PFPS. Data are
      inconclusive regarding the use of patellar taping, patellar bracing, knee
      bracing, and foot orthosis. Although emerging data suggest the importance of hip
      strengthening exercise, ongoing investigations are needed to better understand
      its effect on PFPS. CONCLUSIONS: Current evidence supports the continued use of
      quadriceps exercise for the conservative management of PFPS. However,
      inconsistent or limited data regarding the other interventions precluded the
      authors' ability to make conclusive recommendations about their use. Future
      investigations should focus on identifying cohorts of patients with PFPS who may
      benefit from the other treatment approaches included in this systematic review.

PMID- 21713230
TI  - Exertional compartment syndrome: review of the literature and proposed
      rehabilitation guidelines following surgical release.
AB  - BACKGROUND: There is little published information regarding postoperative
      management of patients with Chronic Exertional Compartment Syndrome (CECS).
      Reports of recurrence of symptoms following surgical decompression exist, and are
      not uncommon depending on the specific technique used. Recurrence suggests that
      more time and effort may need to be spent on implementing strategic post
      operative rehabilitation management in order to avoid repeat surgical
      intervention or prolonged symptoms. OBJECTIVE: To summarize relevant literature
      regarding CECS and propose scientifically-based guidelines for rehab following
      compartment release with the rationale based on tissue healing, muscle loading,
      and scar tissue formation and consideration of all tissues contained in the
      involved compartment. LITERATURE REVIEW: A LITERATURE SEARCH WAS PERFORMED IN
      PUBMED, SPORTDISCUS, CINAHL, PEDRO, AND GOOGLE SCHOLAR USING THE PHRASE: "chronic
      exertional compartment syndrome." RESULTS: No specific rehabilitation guidelines
      following surgical compartment release for lower extremity CECS were found in the
      literature search performed for this clinical commentary. DISCUSSION: The
      development of the proposed post-operative guidelines may allow for improved long
      term outcomes following anterior compartment release. SUMMARY: Adequate
      description of long-term follow-up of outcomes following compartment release for
      CECS is lacking in current literature. The proposed guidelines for rehab
      following compartment release include consideration of tissue healing, muscle
      loading, scar tissue formation, and consideration of soft tissues contained in
      the involved compartment. Utilization of the proposed guidelines may allow for
      future research to be performed in order to assess outcomes following surgical
      intervention for CECS.

PMID- 21713231
TI  - Hip muscle activation and knee frontal plane motion during weight bearing
      therapeutic exercises.
AB  - PURPOSE/BACKGROUND: Hip abduction strengthening exercises may be critical in the
      prevention and rehabilitation of both overuse and traumatic injuries where knee
      frontal plane alignment is considered to be important. The purpose of the current
      investigation was to examine the muscular activation of the gluteus maximus and
      gluteus medius during the double-leg squat (DLS), single-leg squat (SLS), or
      front step-up (FSU), and the same exercises when an added load was used to pull
      the knee medially. METHODS: Eighteen healthy females (ages 18-26) performed six
      exercises: DLS, DLS with load, FSU, FSU with load, SLS, and SLS with load.
      Integrated and peak surface electromyography of gluteus maximus and gluteus
      medius of the dominant leg were recorded and normalized. Motion analysis was used
      to measure knee abduction angle during each exercise. RESULTS: SLS had the
      highest integrated and peak activation for both muscles, regardless of load.
      Adding load, only increased DLS integrated gluteus maximus activation (p=0.019).
      Load did not increase integrated gluteus medius or peak gluteus maximus
      activation. Adding load decreased SLS peak gluteus medius activation (p=0.003).
      Adding load increased peak knee abduction angle during DLS (p=0.013), FSU
      (p=0.000), and SLS (p=0.011). CONCLUSIONS: Overall, the SLS was most effective
      exercise for activating the gluteus maximus and gluteus medius. Applied knee load
      does not appear to increase muscle activation during SLS and FSU. DLS with an
      applied load may be more beneficial in activating the gluteus maximus. Overall,
      the use of applied loads appears to promote poorer musculoskeletal alignment in
      terms of peak knee valgus angle. LEVEL OF EVIDENCE: 3.

PMID- 21713232
TI  - Effect of topical menthol on ipsilateral and contralateral superficial blood flow
      following a bout of maximum voluntary muscle contraction.
AB  - PURPOSE/BACKGROUND: Various doses of topical menthol are commonly applied prior
      to, during, and after exercise to relieve pain although there is limited
      empirical evidence examining the physiological effects of this treatment. The
      purpose of this study was to examine the effects of two different doses of
      menthol (3.5% and 10%) on blood flow and arterial diameter before and after an
      acute bout of three isokinetic maximum voluntary muscular contraction (MVMC) of
      the quadriceps and hamstrings. METHODS: Blood flow and arterial diameter of the
      right and left popliteal arteries were measured with an ultrasound Doppler prior
      to and after subjects completed 1 set of 3 MVMC isokinetic knee extension/flexion
      exercises. Immediately following this exercise one of three different treatment
      conditions was randomly applied to the right thigh only; 3.5% menthol gel, 10%
      menthol wipe, or a control condition. Five minutes following the treatment
      application blood flow through both right and left popliteal arteries was
      reassessed. This procedure was completed once per week until each of the 16
      subjects was exposed to each treatment condition. RESULTS: Repeated measures
      ANOVA with post hoc analysis indicated that both menthol dosages resulted in
      significant decreases in popliteal blood flow on the right (-19.60 to -8.39%) and
      left sides (-14.72 to -5.4%) while the control condition demonstrated an increase
      in blood flow bilaterally (+26.40 to +15.19%) as a result of the MVMC exercise.
      The right popliteal arterial diameter was also significantly reduced as a result
      of both menthol dosages (-5.73 to -6.73%) and increased under the control
      condition (+6.67%). CONCLUSION: These results indicate that topical menthol has a
      rapid effect on reducing ipsilateral and contralateral arterial blood flow as
      well as ipsilateral arterial diameter. LEVELS OF EVIDENCE: 2a.

PMID- 21713233
TI  - Cortical visual impairment in children - A new challenge for the future?

PMID- 21713234
TI  - Combined intravitreal bevacizumab with phacoemulsification in visually
      significant cataract and visually significant exudative maculopathy.
AB  - PURPOSE: We investigated the visual outcome of combined phacoemulsification with
      intravitreal bevacizumab, in eyes with dense cataract and visually significant
      exudative maculopathy. MATERIALS AND METHODS: Prospective longitudinal pilot
      study of consecutive patients treated by two surgeons in 2006, using intravitreal
      bevacizumab at the end of phacoemulsification. The historical control group
      consisted of consecutive subjects with exudative maculopathy and dense cataract
      treated by the same surgeons with the help of phacoemulsification without
      intravitreal bevacizumab prior to 2006. RESULTS: Thirty-one treated patients had
      the mean (SD) logMar best corrected visual acuity improving from - 1.48 (0.50)
      preoperatively to - 0.67 (0.38) in the first postoperative week (P < 0.001), to -
      0.64 (0.40) in the first postoperative month (P < 0.001), and to - 0.62 (0.42) (P
      < 0.001) on the last follow-up (mean 4.2 months, range 1 - 9 months). Fourteen
      control patients had the mean (SD) logMar best corrected visual acuity improving
      from - 1.78 (0.79) preoperatively, to - 0.91 (0.53) in the first postoperative
      week (P < 0.001), to - 0.86 (0.45) in the first postoperative month (P < 0.001),
      and to - 0.90 (0.47) (P < 0.001) on the last follow- up (mean 19.6 months, range
      1 - 49 months). Initial visual acuities, final visual acuities, and percentage of
      visual improvement at one month were all not significantly better in the
      intervention compared to the control group at one month. In the study group, the
      fovea was flattened at the one-month follow-up, by 90-diopter slit lamp
      examination and / or Optical coherence tomography. CONCLUSION: The combination of
      intravitreal bevacizumab and phacoemulsification is beneficial for maximal visual
      rehabilitation in the first postoperative month.

PMID- 21713235
TI  - Ocular status and functional adaptation of visually challenged children of a
      special school in Oman.
AB  - INTRODUCTION: We assessed the ocular status and visual adaptation among children
      studying at a school for visually disabled children in Muscat, Oman. MATERIALS
      AND METHODS: This descriptive study was conducted in 2009-2010. We assessed the
      visual and ocular status of the participants. They were interviewed to elicit the
      past history of eye problems and management. They also expressed their visual
      adaptation in their 'day-to-day' life, and their ambitions. RESULT: We examined
      and interviewed 47 participants (29 male and 18 female). The mean age of the
      participants was 19.7 years (Standard deviation 5.9 years). Twenty-six of them
      were blind since birth. Phthisical eyes, disfigured eyes and anophthalmic sockets
      were noted in 19, 58, and six eyes of participants. Twenty-six (55.5%)
      participants had visual disabilities due to genetic causes, since birth. In 13
      participants, further investigations were needed to confirm diagnosis and
      determine further management After low vision training, 13 participants with
      residual vision could be integrated in the school with normal children. One
      participant was recommended stem cell treatment for visual restoration. Five
      children were advised reconstructive orbital surgery. The participants were not
      keen to use a white cane for mobility. Some participants, 16 / 28 (57%), with
      absolute blindness, were not able to read the Braille language. Singing and
      playing music were not very well-accepted hobbies among the participants.
      Nineteen participants were keen to become teachers. CONCLUSIONS: Children with
      visual disabilities need to be periodically assessed. The underlying causes of
      visual disabilities should be further explored to facilitate prevention and
      genetic counseling. Participants had visual adaptation for daily living and had
      ambitions for the future.

PMID- 21713236
TI  - Role of antimetabolites in recalcitrant idiopathic orbital inflammatory syndrome.
AB  - BACKGROUND: High-dose systemic steroids are the primary modality of treatment for
      idiopathic orbital inflammatory syndrome (IOIS). Occasionally patients experience
      a relapse of symptoms on tapering steroids or require large doses of steroid,
      predisposing them to the adverse effects of steroids. AIM: We present our
      experience with the management of three patients with recalcitrant IOIS, with
      immunosuppressive therapy, using antimetabolites. MATERIALS AND METHODS: A
      retrospective review of the medical records of the patients being reported.
      RESULTS: Two patients were treated with Methotrexate and one with Azathioprine
      for a duration of 6-24 months. Two patients were symptom-free three years after
      stopping the medication. One was doing well clinically with methotrexate therapy
      alone, when he was lost to follow-up after six months. No adverse effects of
      immunosuppressive therapy were encountered. CONCLUSION: High-dose systemic
      steroid therapy is the first-line treatment for IOIS, but in refractory or
      steroid-dependent cases, immunosuppressive therapy with antimetabolites is a safe
      and effective treatment alternative to steroids. However, treatment with
      antimetabolites warrants close monitoring for complications like bone marrow
      suppression and liver dysfunction, especially because long-term treatment is
      required.

PMID- 21713237
TI  - A rare case of adult onset retinoblastoma.
AB  - Retinoblastoma usually manifests before five years of age. Retinoblastoma in an
      adult is extremely rare. Twenty-three cases of retinoblastoma in adults 20 years
      or older have been reported in world literature. We report a case of adult onset
      retinoblastoma in a 29-year-old female. Our patient had unilateral endophytic
      retinoblastoma with vitreous seeds and calcification on ultrasonography. She
      underwent enucleation with silicone ball implantation and the diagnosis was
      confirmed histopathologically. The diagnosis of retinoblastoma should be kept in
      mind in cases presenting with a white mass lesion of unknown etiology, in the
      fundus of an adult.

PMID- 21713238
TI  - Hemorrhagic intraretinal macrocyst: Differential diagnoses and report of an
      unusual case.
AB  - Retinal 'cysts' may be single or multiple, ranging from two-to-ten disc diameters
      in size, and occur in eyes with longstanding retinal detachment. The authors
      describe a retinal macrocyst larger than ten disc diameters, with a blood-filled
      cavity, and its ultrasound findings. Improved retinal nourishment following
      retinal reattachment gradually reverses the process responsible for cystic
      degeneration, with the eventual collapse of the cyst (within days or weeks).
      Surprisingly, this giant cyst did not collapse for almost three years despite
      retinal reattachment. The internal mobile echogenic contents were suggestive of
      blood. The possible reason of blood in the cyst could be rupture of the retinal
      blood vessels in the cyst cavity. This could be a recurrent phenomenon, which did
      not allow the cyst to collapse. The Hemorrhagic Intraretinal Macrocyst needs to
      be differentiated from mimicking clinical conditions, namely, retinoschisis,
      choroidal melanoma, subretinal abscess, choroidal hemangioma, and the like. It
      could take up to a few years to collapse spontaneously, following successful
      retinal reattachment.

PMID- 21713240
TI  - Sudden onset isolated complete third nerve palsy due to pituitary apoplexy.

PMID- 21713239
TI  - Inflammatory glaucoma.
AB  - Glaucoma is seen in about 20% of the patients with uveitis. Anterior uveitis may
      be acute, subacute, or chronic. The mechanisms by which iridocyclitis leads to
      obstruction of aqueous outflow include acute, usually reversible forms (e.g.,
      accumulation of inflammatory elements in the intertrabecular spaces, edema of the
      trabecular lamellae, or angle closure due to ciliary body swelling) and chronic
      forms (e.g., scar formation or membrane overgrowth in the anterior chamber
      angle). Careful history and follow-up helps distinguish steroid-induced glaucoma
      from uveitic glaucoma. Treatment of combined iridocyclitis and glaucoma involves
      steroidal and nonsteroidal antiinflammatory agents and antiglaucoma drugs.
      However, glaucoma drugs can often have an unpredictable effect on intraocular
      pressure (IOP) in the setting of uveitis. Surgical intervention is required in
      case of medical failure. METHOD OF LITERATURE SEARCH: Literature on the Medline
      database was searched using the PubMed interface.

PMID- 21713241
TI  - Congenital bilateral ectropion in lamellar ichthyosis.

PMID- 21713242
TI  - Retinal pigment epithelial changes after trypan blue-assisted internal limiting
      membrane peeling for idiopathic macular hole.

PMID- 21713243
TI  - 67-year-old male with right eye discharge.

PMID- 21713244
TI  - Optic nerve infiltration in relapse of acute lymphoblastic leukemia.

PMID- 21713245
TI  - Combined posterior flap and anterior suspended flap external
      dacryocystorhinostomy.

PMID- 21713246
TI  - Novelty vs. Familiarity Principles in Preference Decisions: Task-Context of Past
      Experience Matters.
AB  - Our preferences are shaped by past experience in many ways, but a systematic
      understanding of the factors is yet to be achieved. For example, studies of the
      mere exposure effect show that experience with an item leads to increased liking
      (familiarity preference), but the exact opposite tendency is found in other
      studies utilizing dishabituation (novelty preference). Recently, it has been
      found that image category affects whether familiarity or novelty preference
      emerges from repeated stimulus exposure (Park et al., 2010). Faces elicited
      familiarity preference, but natural scenes elicited novelty preference. In their
      task, preference judgments were made throughout all exposures, raising the
      question of whether the task-context during exposure was involved. We adapt their
      paradigm, testing if passive exposure or objective judgment task-contexts lead to
      different results. Results showed that after passive viewing, familiar faces were
      preferred, but no preference bias in either direction was found with natural
      scenes, or with geometric figures (control). After exposure during the objective
      judgment task, familiar faces were preferred, novel natural scenes were
      preferred, and no preference bias was found with geometric figures. The overall
      results replicate the segregation of preference biases across object categories
      and suggest that the preference for familiar faces and novel natural scenes are
      modulated by task-context memory at different processing levels or selection
      involvement. Possible underlying mechanisms of the two types of preferences are
      discussed.

PMID- 21713247
TI  - Stress and coping with discrimination and stigmatization.
AB  - The aim of this article is to briefly review the literature on stigmatization and
      more generally identity threats, to focus more specifically of the way people
      appraise and cope with those threatening situations. Based on the transactional
      model of stress and coping of Lazarus and Folkman (1984), we propose a model of
      coping with identity threats that takes into accounts the principle
      characteristic of stigma, its devaluing aspect. We present a model with specific
      antecedents, a refined appraisal phase and a new classification of coping
      strategies based on the motives that may be elicited by the threatening
      situation, those of protecting and/or enhancing the personal and/or social
      identity.

PMID- 21713248
TI  - Stabilization of photosensitizing dyes by complexation with clay.
AB  - Synthetic saponites containing photosensitizing dyes (1,1'-diethyl-2,2'-cyanine
      (pseudoisocyanine) or tris(2,2'-bipyridine)ruthenium(II)) in the interlayer space
      were complexed with nanocrystalline anatase. The photostability of the dyes in
      the dye-clay-anatase hybrids upon visible light irradiation was improved,
      possibly because of the separation of the dyes from the anatase surface by the
      thin clay layer.

PMID- 21713249
TI  - Direct assembly synthesis of metal complex-semiconductor hybrid photocatalysts
      anchored by phosphonate for highly efficient CO2 reduction.
AB  - Hybrid photocatalysts consisting of a ruthenium complex and p-type photoactive N
      doped Ta(2)O(5) anchored with an organic group were successfully synthesized by a
      direct assembly method. The photocatalyst anchored by phosphonate exhibited
      excellent photoconversion activity of CO(2) to formic acid under visible-light
      irradiation with respect to the reaction rate and stability.

PMID- 21713250
TI  - Synthesis of a polythieno[3,4-b]thiophene derivative with a low-lying HOMO level
      and its application in polymer solar cells.
AB  - A planar benzodithiophene with lower HOMO was copolymerized with the thieno[3,4
      b]thiophene unit to obtain a new low band gap polymer of PBDPTT-C, which
      exhibited a higher open-circuit voltage (V(oc)) of 0.8 V and a promising
      efficiency of 5.2%.

PMID- 21713251
TI  - Highly fluorescent M2L4 molecular capsules with anthracene shells.
AB  - M(2)L(4) molecular capsules self-assembled from M(II) ions (where M = Zn, Ni, and
      Pd) and bent bidentate ligands constructed from anthracene fluorophores. The
      Ni(II) and Zn(II) capsules exhibited weak to strong blue emission unlike
      traditional Pd(II) cages and capsules.

PMID- 21713261
TI  - High temperatures enhance cooperative motions between CBM and catalytic domains
      of a thermostable cellulase: mechanism insights from essential dynamics.
AB  - Cellulases from thermophiles are capable of cleaving sugar chains from cellulose
      efficiently at high temperatures. The thermo-resistant Cel9A-68 cellulase
      possesses two important domains: CBM and a catalytic domain connected by a
      Pro/Ser/Thr rich linker. These domains act cooperatively to allow efficient
      catalysis. Despite exhaustive efforts to characterize cellulase binding and
      mechanism of action, a detailed description of the cellulose intrinsic
      flexibility is still lacking. From computational simulations we studied the
      temperature influence on the enzyme plasticity, prior to substrate binding.
      Interestingly, we observed an enhancement of collective motions at high
      temperatures. These motions are the most representative and describe an intrinsic
      hinge bending transition. A detailed analysis of these motions revealed an
      interdomain approximation where D459 and G460, located at the linker region, are
      the hinge residues. Therefore, we propose a new putative site for mutagenesis
      targeting the modulation of such conformational transition that may be crucial
      for activity.

PMID- 21713262
TI  - Reversible chain association/dissociation via a CO2 responsive
      crosslinking/decrosslinking system.
AB  - Reversible chain association/dissociation phenomenon via CO(2) responsive
      crosslinking/decrosslinking was detected in aqueous solutions of polyallylamine
      (PAA). The chain association/dissociation behavior was reversible and useful in
      the synthesis of porous crosslinked polystyrene, which suggested potential
      utility in the area of CO(2)-responsive separable adhesives, switches and
      sensors.

PMID- 21713263
TI  - Cucurbit[n]uril based supramolecular assemblies: tunable physico-chemical
      properties and their prospects.
AB  - This Feature Article provides an account of the recent work by our research group
      (with some reference to relevant work of other groups) on the spectacular physico
      chemical properties of cucurbituril-based supramolecular assemblies of
      chromophoric dyes having technological and biological importance. Simultaneous
      association of multiple hosts or guests either by cooperative binding or
      competitive displacement is an applied strategy to construct novel functional
      assemblies with predesignated characteristics. Here, effort has been made to
      briefly discuss the diverse photophysical characteristics of several host-guest
      complexes and the dynamic responses of such molecular assemblies towards external
      stimulants like metal ions. The detailed experimentation on these assemblies
      project their applications in the controlled uptake and release of drugs,
      photofunctional devices, aqueous-based dye lasers, and molecular architectures.

PMID- 21713264
TI  - A facile one-pot synthesis of uniform core-shell silver nanoparticle@mesoporous
      silica nanospheres.
AB  - The uniform core-shell silver nanoparticle@mesoporous silica nanospheres have
      been prepared by a simple one-pot synchronous method, which combines several
      steps into one, including the generation of silver nanocrystals and mesoporous
      silica, transfer and aggregation of silver nanoparticles in an incompact silica
      framework.

PMID- 21713265
TI  - Unique photoemission from single-layer graphene on a SiO2 layer by a substrate
      charging effect.
AB  - Single-layer graphene (SLG) shows an anomalously large surface charging effect
      during scanning photoelectron microscopy (SPEM), which is distinguished from bi
      layer graphene (BLG). The different behaviour is believed due to a different
      screening effect for SLG and BLG.

PMID- 21713266
TI  - CO oxidation catalyzed by a single gold atom: benchmark calculations and the
      performance of DFT methods.
AB  - Quantum chemical calculations were carried out on CO oxidation catalyzed by a
      single gold atom. To investigate the performance of density functional theory
      (DFT) methods, 42 DFT functionals have been evaluated and compared with high
      level wavefunction based methods. It was found that in order to obtain accurate
      results the functionals used must treat long range interaction well. The double
      hybrid mPW2PLYP and B2PLYP functionals are the two functionals with best overall
      performance. CAM-B3LYP, a long range corrected hybrid GGA functional, also
      performs well. On the other hand, the popular B3LYP, PW91, and PBE functionals do
      not show good performance and the performance of the latter two are even at the
      bottom of the 42 functionals. Our accurate results calculated at the CCSD(T)/aug
      cc-pVTZ//mPW2PLYP/aug-cc-pVTZ level of theory indicate that Au atom is a good
      catalysis for CO oxidation. The reaction follows the following mechanism where CO
      and O(2) adsorb on Au atom forming an Au(OCOO) intermediate and subsequently O(2)
      transfer one oxygen atom to CO to form CO(2) and AuO. Then AuO reacts with CO to
      form another CO(2) to complete the catalytic cycle. The overall energy barrier at
      0 K for the first CO oxidation step (Au + CO + O(2)-> AuO + CO(2)) is just 4.8
      kcal mol(-1), and that for the second CO oxidation step (AuO + CO -> Au + CO(2))
      is just 1.6 kcal mol(-1).

PMID- 21713267
TI  - Controlled growth of single-walled carbon nanotubes on patterned substrates.
AB  - Single-walled carbon nanotubes (SWCNTs) have attracted great interest in the last
      two decades because of their unique electrical, optical, thermal, mechanical
      properties, etc. One major research field of SWCNTs is the controlled growth of
      them from the patterned catalysts on substrates, since the integration of SWCNTs
      into nanoelectronics and other devices requires well-organized SWCNT arrays. This
      tutorial review describes the commonly used lithographic techniques to pattern
      catalysts used for controlled growth of SWCNTs, specifically confined to the
      horizontal direction. Advantages and disadvantages of each method will be briefly
      discussed. Applications of the SWCNT arrays grown from the catalyst patterns will
      also be introduced.

PMID- 21713268
TI  - Transformations of biomass-derived platform molecules: from high added-value
      chemicals to fuels via aqueous-phase processing.
AB  - Global warming issues and the medium-term depletion of fossil fuel reserves are
      stimulating researchers around the world to find alternative sources of energy
      and organic carbon. Biomass is considered by experts the only sustainable source
      of energy and organic carbon for our industrial society, and it has the potential
      to displace petroleum in the production of chemicals and liquid transportation
      fuels. However, the transition from a petroleum-based economy to one based on
      biomass requires new strategies since the petrochemical technologies, well
      developed over the last century, are not valid to process the biomass-derived
      compounds. Unlike petroleum feedstocks, biomass derived platform molecules
      possess a high oxygen content that gives them low volatility, high solubility in
      water, high reactivity and low thermal stability, properties that favour the
      processing of these resources by catalytic aqueous-phase technologies at moderate
      temperatures. This tutorial review is aimed at providing a general overview of
      processes, technologies and challenges that lie ahead for a range of different
      aqueous-phase transformations of some of the key biomass-derived platform
      molecules into liquid fuels for the transportation sector and related high added
      value chemicals.

PMID- 21713269
TI  - Evidence of highly dynamic geochemical behaviour of zinc in the Deule river
      (northern France).
AB  - The monitoring of dissolved zinc in the Deule river was undertaken at three
      different periods of the years 2008 and 2009. Electrolabile concentrations of Zn
      were estimated every 2 hours for several weeks by using an ATMS (Automatic Trace
      metal Monitoring System) based on voltammetric measurements using a solid Ag-Hg
      rotating disc working electrode. Complementary measurements were carried out with
      DGT (Diffusive Gradient in Thin films) pistons deployed directly in the river for
      24 hours. Water samples filtrated at 0.45 MUm were also analysed by HR-ICP-MS to
      estimate the total dissolved concentrations of zinc and other trace metals. High
      frequency monitoring of zinc over several weeks in the Deule river indicated that
      the concentration could change significantly over short time periods.
      Resuspension of polluted sediment and biological activities are two main factors
      that control the behaviour of zinc in the Deule river. Furthermore, in May 2009,
      daily cycles of the electrolabile zinc fraction have been observed at relatively
      constant total dissolved concentration. It is assumed that this particular
      behaviour of zinc is based on an exchange between colloids and/or
      nonelectrolabile forms and free cation and inorganic complexes at a daily time
      scale.

PMID- 21713270
TI  - Serum metabolic profiling and features of papillary thyroid carcinoma and nodular
      goiter.
AB  - Thyroid carcinoma is a common endocrine malignancy worldwide, accounting for
      approximately 1% of all diagnosed cancers and about 91.5% of the malignancies of
      head and neck. However, differentiating malignant thyroid nodules from benign
      ones remains a diagnostic challenge. Thus, novel molecular markers that enable
      non-invasive diagnostics for malignant thyroid nodules are urgently needed. In
      the present study, a metabonomic investigation based on liquid chromatography-LTQ
      Orbitrap mass spectrometry was employed for serum metabolic profiling of 30 cases
      of papillary thyroid carcinomas (PTC), 80 cases of nodular goiters (benign
      thyroid nodules) and 30 cases of healthy controls. According to the results of
      multivariate statistical data analysis, the significantly changed metabolites
      among these three groups were defined. It was found that most of these
      metabolites decreased in the sera of both malignant and benign thyroid cases due
      to the increased metabolic rate, which is in accordance with clinical features.
      The major metabolic differences between benign and malignant nodules occurred in
      lipid metabolism. Especially, the content of 3-hydroxybutyric acid, an
      intermediate product of fatty acid metabolism, was much higher in the PTC group
      than that in the nodule goiter and control groups, indicating its potential as a
      diagnostic marker for PTC and nodular goiters. These results show that the serum
      metabolic profiling method is a powerful tool for distinguishing thyroid
      carcinoma from nodular goiter and healthy controls.

PMID- 21713271
TI  - Diterpenoids of terrestrial origin.

PMID- 21713272
TI  - Trophic transfer of amphiphilic polymer coated CdSe/ZnS quantum dots to Danio
      rerio.
AB  - To investigate the trophic transfer of nanomaterials along the food chain, we
      examined the potential trophic transfer and biomagnification of CdSe/ZnS quantum
      dots (QDs) in a simple freshwater food chain. Our results indicate that QDs can
      transfer from zooplankton to Danio rerio (zebrafish) by dietary exposure. No
      significant biomagnification of QDs was observed and the biomagnification factors
      for both adult and juvenile zebrafish were both less than one (0.04 and 0.004
      respectively). The assimilation efficiency was 8% and 4% for adult and juvenile
      zebrafish respectively. This study is the first to examine the potential food
      chain transfer and biomagnification of QDs from zooplankton to zebrafish.

PMID- 21713273
TI  - Graphene nanosheets-polypyrrole hybrid material as a highly active catalyst
      support for formic acid electro-oxidation.
AB  - A novel electrode material based on graphene oxide (GO)-polypyrrole (PPy)
      composites was synthesized by in situ chemical oxidation polymerization.
      Palladium nanoparticles (NPs) with a diameter of 4.0 nm were loaded on the
      reduced graphene oxide(RGO)-PPy composites by a microwave-assisted polyol
      process. Microstructure analysis showed that a layer of coated PPy film with
      monodisperse Pd NPs is present on the RGO surface. The Pd/RGO-PPy catalysts
      exhibit excellent catalytic activity and stability for formic acid electro
      oxidation when the weight feed ratio of GO to pyrrole monomer is 2:1. The
      superior performance of Pd/RGO-PPy catalysts may arise from utilization of
      heterogeneous nucleation sites for NPs and the greatly increased electronic
      conductivity of the supports.

PMID- 21713274
TI  - Cu2ZnSnS4 nanocrystals and graphene quantum dots for photovoltaics.
AB  - Semiconductor quantum dots exhibit great potential for applications in next
      generation high efficiency, low cost solar cells because of their unique
      optoelectronic properties. Cu(2)ZnSnS(4) (CZTS) nanocrystals and graphene quantum
      dots (GQDs) have recently received much attention as building blocks for use in
      solar energy conversion due to their outstanding properties and advantageous
      characteristics, including high optical absorptivity, tunable bandgap, and earth
      abundant chemical composition. In this Feature Article, recent advances in the
      synthesis and utilization of CZTS nanocrystals and colloidal GQDs for
      photovoltaics are highlighted, followed by an outlook on the future research
      efforts in these areas.

PMID- 21713275
TI  - Reduction of isoviolanthrone by reaction with photogenerated radicals.
AB  - The properties of isoviolanthrone (V(1)) and its corresponding dihydro form (V(1)
      H(2)) in argon-saturated 1-phenylethanol in the presence of acetophenone were
      examined by photophysical and photochemical methods. Upon photolysis of the
      sensitizer, a radical-induced reduction of V(1) to V(1)-H(2) occurs. The quantum
      yield of this reduction is close to unity. The fluorescence of V(1) has a quantum
      yield of 0.08, for V(1)-H(2)Phi(f) is strongly enhanced and the emission maximum
      is blue-shifted. The ketyl radical, the semiquinone radical and V(1)-H(2) were
      observed in this sequence by flash photolysis. V(1)-H(2) is unstable and
      undergoes oxidation to V(1) on admission of oxygen.

PMID- 21713276
TI  - Chemical studies on the BRET system between the bioluminescence of Cypridina and
      quantum dots.
AB  - We report a bioluminescence resonance energy transfer (BRET) system between
      Cypridina luciferase (Cluc) and QDs. After coupling of the biotinylated Cluc with
      streptavidin-QDs, a BRET emission of QDs through the resonance energy transfer
      from the oxidation of Vargula (Cypridina) luciferin was observed. A luciferin
      analogue having a naphtyl group at C6-position showed a large blue shift of the
      emission spectrum, which improved the ratio of this BRET system. After directly
      conjugating the luciferase with QDs, an efficient BRET was observed similar to
      the previous BRET using organic dyes. Furthermore, the symmetric emission spectra
      of QDs show a potential to realize multiplexed imaging based on the BRET of Cluc
      using the same luciferin.

PMID- 21713277
TI  - UV-induced immunosuppression and the efficacy of vaccination.
AB  - Exposure to ultraviolet radiation (UVR) suppresses immunity by complex pathways,
      initiated by chromophores located in the skin and ending with the generation of
      specific subsets of T and B regulatory cells. The primary and memory (recall)
      immune response to a wide variety of antigens, including microorganisms, can be
      reduced by UVR, leading to the possibility that the efficacy of vaccination could
      be similarly reduced. A limited number of animal models of vaccination
      demonstrate that this may indeed be the case. The situation in human subjects has
      not been rigorously assessed but there are indications from a variety of sources
      that UVR adversely affects the immune responses to several vaccines. These
      studies are reviewed and the implications for vaccine administration discussed.
      As vaccination represents a major public health measure world-wide for the
      control of an increasing number of common infections, it is important to maximise
      its efficacy; therefore further evaluation of UVR in the context of vaccination
      is required and warranted.

PMID- 21713278
TI  - Metall(prote)omic studies by capillary electrophoresis using separation capillary
      as an in-line reactor.
AB  - This perspective article highlights the potential of capillary electrophoresis
      (CE) in in-line monitoring of biomolecular reactions related to in vivo
      transformations of metal species. In such scrutinizing, the capillary is regarded
      as a nanolitre-volume reactor in which electrical field-driven reactants are
      mixed to produce a response that enables in situ following-up and
      characterization of non-covalent molecular interactions. The concept of a CE
      reactor has been extended here to the investigation of processes that are
      responsible for the formation and decomposition of metal-bioligand species under
      simulated physiological conditions.

PMID- 21713279
TI  - Mono-acylation of a polyamine-beta-cyclodextrin based on guest mediated acyl
      migration.
AB  - The S -> N acylation rates of thioester functionalized coumarins on heptakis-[6
      deoxy-6-(2-aminoethylsulfanyl)]-beta-cyclodextrin were measured. A high yield of
      mono-acylation was achieved with products that form self-inclusion compounds. The
      differential fluorescence response of the functionalized cyclodextrins upon
      binding biomacromolecules shows the potential of the constructs as probes.

PMID- 21713280
TI  - Electrical conductive coordination polymers.
AB  - Coordination polymers are currently one of the hottest topics in Inorganic and
      Supramolecular Chemistry. This critical review summarizes the current state-of
      the-art on electrical conductive coordination polymers (CPs), also named metal
      organic frameworks (MOFs). The data were collected following two sort criteria of
      the CPs structure: dimensionality and bridging ligands (151 references).

PMID- 21713281
TI  - Modeling synergistic drug inhibition of Mycobacterium tuberculosis growth in
      murine macrophages.
AB  - We developed a metabolism-based systems biology framework to model drug-induced
      growth inhibition of Mycobacterium tuberculosis in murine macrophage cells. We
      used it to simulate ex vivo bacterial growth inhibition due to 3-nitropropionate
      (3-NP) and calculated the corresponding time- and drug concentration-dependent
      dose-response curves. 3-NP targets the isocitrate lyase 1 (ICL1) and ICL2 enzymes
      in the glyoxylate shunt, an essential component in carbon metabolism of many
      important prokaryotic organisms. We used the framework to in silico mimic
      drugging additional enzymes in combination with 3-NP to understand how synergy
      can arise among metabolic enzyme targets. In particular, we focused on exploring
      additional targets among the central carbon metabolism pathways and ascertaining
      the impact of jointly inhibiting these targets and the ICL1/ICL2 enzymes. Thus,
      additionally inhibiting the malate synthase (MS) enzyme in the glyoxylate shunt
      did not produce synergistic effects, whereas additional inhibition of the
      glycerol-3-phosphate dehydrogenase (G3PD) enzyme showed a reduction in bacterial
      growth beyond what each single inhibition could achieve. Whereas the ICL1/ICL2-MS
      pair essentially works on the same branch of the metabolic pathway processing
      lipids as carbon sources (the glyoxylate shunt), the ICL1/ICL2-G3PD pair
      inhibition targets different branches among the lipid utilization pathways. This
      allowed the ICL1/ICL2-G3PD drug combination to synergistically inhibit carbon
      processing and ultimately affect cellular growth. Our previously developed model
      for in vitro conditions failed to capture these effects, highlighting the
      importance of constructing accurate representations of the experimental ex vivo
      macrophage system.

PMID- 21713282
TI  - DIPOS: database of interacting proteins in Oryza sativa.
AB  - Rice is an important crop throughout the world and is the staple food for about
      half the world's population. For better breeding and improved production, we need
      to know the function of rice molecules which facilitate their function through
      interactions with each other. The database of interacting proteins in Oryza
      sativa (DIPOS) provides comprehensive information of interacting proteins in
      rice, where the interactions are predicted using two computational methods, i.e.,
      interologs and domain based methods. DIPOS contains 14 614 067 pairwise
      interactions among 27 746 proteins, covering about 41% of the whole Oryaza sativa
      proteome. Furthermore, each interaction is assigned a confidence score which
      further enables biologists to sort out the important proteins. Biological
      explanations of pathways and interactions are also provided based on the
      database. Public access to the DIPOS is available at and .

PMID- 21713283
TI  - Proteomic responses in Arabidopsis thaliana seedlings treated with ethylene.
AB  - Ethylene (ET) is a volatile hormone that modulates fruit ripening, plant growth,
      development and stress responses. Key components of the ET-signaling pathway
      identified by genetic dissection in Arabidopsis thaliana include five ET
      receptors, the negative regulator CTR1 and the positive regulator EIN2, all of
      which localize to the endoplasmic reticulum. Mechanisms of signaling among these
      proteins are still unresolved and targets of ET responses are not fully known.
      So, we used mass spectrometry to identify proteins in microsomal membrane
      preparations from etiolated A. thaliana seedlings maintained in ambient air or
      treated with ET for 3 h. We compared 3814 proteins from ET-exposed seedlings and
      controls and identified 304 proteins with significant accumulation changes. The
      proteins with increased accumulation were involved in ET biosynthesis, cell
      morphogenesis, oxidative stress and vesicle secretion while those with decreased
      accumulation were ribosomal proteins and proteins positively regulated by
      brassinosteroid, another hormone involved in cell elongation. Several proteins,
      including EIN2, appeared to be differentially phosphorylated upon ET treatment,
      which suggests that the activity or stability of these proteins may be controlled
      by phosphorylation. TUA3, a component of microtubules that contributes to
      cellular morphological change, exhibited both increased accumulation and
      differential phosphorylation upon ET treatment. To verify the role of TUA3 in the
      ET response, tua3 mutants were evaluated. Mutant seedlings had altered ET
      associated growth movements. The data indicate that ET perception leads to rapid
      proteomic change and that these changes are an important part of signaling and
      development. The data serve as a foundation for exploring ET signaling through
      systems biology.

PMID- 21713284
TI  - Electrospinning induced ferroelectricity in poly(vinylidene fluoride) fibers.
AB  - Poly(vinylidene fluoride) (PVDF) fibers with diameters ranging from 70 to 400 nm
      are produced by electrospinning and the effect of fiber size on the ferroelectric
      beta-crystalline phase is determined. Domain switching and associated ferro
      /piezo-electric properties of the electrospun PVDF fibers were also determined.
      The fibers showed well-defined ferroelectric and piezoelectric properties.

PMID- 21713285
TI  - Bcl-2 family interactome analysis using bacterial surface display.
AB  - Members of the Bcl-2 family of proteins have opposing roles in programmed cell
      death; family members can play either pro-apoptotic or anti-apoptotic roles.
      Heterodimeric interactions between pro-apoptotic and anti-apoptotic members of
      the Bcl-2 family are critical for the regulation of apoptosis and are important
      targets for cancer therapeutics. Bcl-2 family interactions are mediated by the
      highly-conserved BH3 domain, corresponding to a single amphipathic alpha-helix,
      which binds in a hydrophobic cleft of its Bcl-2 family interaction partner. Here,
      using a high-throughput peptide-protein interaction assay based on bacterial cell
      surface display and flow cytometry, we present quantitative data for a near
      complete set of 17 BH3 domains from the human genome binding to each of the 5
      anti-apoptotic Bcl-2 family members. Biophysical insights into the affinity and
      specificity of these interactions are provided by analysis of the interactome
      data. In addition we carried out a truncation study of the Bim BH3 domain to
      define the core residues responsible for anti-apoptotic protein binding. The
      interactome data from this study has implications both in basic research on
      apoptosis and in the design of peptidic cancer therapeutics.

PMID- 21713286
TI  - Chromatographic behaviour of single cells in a microchannel with dynamic
      geometry.
AB  - We present the design of a microchannel with dynamic geometry that imparts
      different flow rates to different cells based on their physical properties. This
      dynamic microchannel is formed between a textured surface and a flexible
      membrane. As cells flow through the microchannel, the height of the channel
      oscillates causing periodic entrapment of the larger cells, and as a result,
      attenuating their velocity relative to the bulk liquid. The smaller cells are not
      slowed by the moving microstructure, and move synchronously with the bulk liquid.
      The ability of the dynamic microchannel to selectively attenuate the flow rate of
      eukaryotic cells is similar to a size-exclusion chromatography column, but with
      the opposite behavior. The speed of smaller substances is attenuated relative to
      the larger substances in traditional size-exclusion chromatography columns,
      whereas the speed of the larger substances that is attenuated in the dynamic
      microchannel. We verified this property by tracking the flow of single cells
      through the dynamic microchannel. L1210 mouse lymphoma cells (MLCs), peripheral
      blood mononuclear cells (PBMCs), and red blood cells (RBCs) were used as model
      cells. We showed that the flow rate of MLC is slowed by more than 50% compared to
      PBMCs and RBCs. We characterized the operation of the microchannel by measuring
      the velocity of each of the three cell types as a function of the pressures used
      to oscillate the membrane position, as well as the duty cycle of the oscillation.

PMID- 21713287
TI  - Facile fabrication of a rigid and chemically resistant micromixer system from
      photocurable inorganic polymer by static liquid photolithography (SLP).
AB  - Highly effective mixing in microchannels is important for most chemical reactions
      conducted in microfluidic chips. To obtain a rigid and chemically resistant
      micromixer system at low cost, we fabricated a Y-shaped microchannel with built
      in mixer structures by static liquid photolithography (SLP) from methacrylated
      polyvinylsilazane (MPVSZ) as an inorganic polymer photoresist which was then
      converted to a silicate phase by hydrolysis in vaporized ammonia atmosphere at 80
      degrees C. The microchannel incorporating herringbone mixer structures was
      bonded with a matching polydimethylsiloxane (PDMS) open channel which was pre
      coated by perhydropolysilazane (PHPS)-based mixture, and finally treated by
      additional hydrolysis at room temperature to convert the PHPS layer to a silica
      phase. Finally, the chemical resistance of the microfluidic system with embedded
      micromixer was confirmed with various solvents, and the excellent mixing
      performance in a short mixing length of 2.3 cm was demonstrated by injecting two
      different colored fluids into the microchannel.

PMID- 21713288
TI  - Continuous electrospinning of polymer nanofibers of Nylon-6 using an atomic force
      microscope tip.
AB  - An atomic force microscopy (AFM) probe is successfully utilized as an
      electrospinning tip for fabricating Nylon-6 nanofibers. The nanometre-size tip
      enabled controlled deposition of uniform polymeric nanofibers within a 1 cm
      diameter area. Nylon-6 nanofibers were continuously electrospun at a solution
      concentration as low as 1 wt% Nylon-6 in 1,1,1,3,3,3-hexafluoro-2-propanol
      (HFIP). Wide-angle X-ray diffraction (WAXD) and differential scanning calorimetry
      (DSC) results of the AFM electrospun fibers indicated that the nanofibers
      predominantly display the meta-stable gamma crystalline form suggesting rapid
      crystallization rate during the process. In addition to precise control over
      fiber deposition and diameter, some of the drawbacks of conventional
      electrospinning such as large volume of solutions and clogging of needles can be
      overcome using this AFM based electrospinning technique. Lastly, a comparison of
      electrospun fibers from syringe-needle based electrospinning and AFM probe-tip
      based electrospinning indicated significant morphological and microstructural
      differences in the case of AFM based electrospinning.

PMID- 21713289
TI  - Hydroboration of an alkene by amine-boranes catalysed by a [Rh(PR3)2]+ fragment.
      Mechanistic insight and tandem hydroboration/dehydrogenation.
AB  - The catalytic hydroboration of tert-butylethene using H(3)B.NMe(3) gives
      RH(2)B.NMe(3). With H(3)B.NMe(2)H tandem hydroboration under mild
      conditions/dehydrocoupling occurs that produces R(2)B=NMe(2) (R = H,
      CH(2)CH(2)(t)Bu).

PMID- 21713290
TI  - Photo- and electroluminescence in thin films of covalently bonded azomethin
      zinc/SiO2 hybrid materials.
AB  - We report the design and chemical synthesis of covalently bonded azomethin
      zinc/SiO(2) hybrid transparent thin films with photoluminescent and
      electroluminescent emissions in condensed solid state by a sol-gel approach.

PMID- 21713291
TI  - Contrasting behaviour of TCNE and TCNQ zwitterionic benzoquinonemonoimine
      derivatives and coordination of a tricyanoethenyl substituent to Pd(0).
AB  - The reaction of TCNE and TCNQ zwitterionic benzoquinonemonoimine derivatives
      under basic conditions resulted in HCN elimination to give a tricyanoethenyl
      derivative - which forms a pi-complex with Pd(0)--or a stable malodinitrile salt,
      respectively. In the latter case, chemoselective C-alkylation was observed
      whereas oxidation led to dimerization by C-C coupling.

PMID- 21713292
TI  - Non-classical hydrogen bonding in [K(1-aza-18-crown-6)]BH4 and its 18-crown-6
      counterpart.
AB  - The extended structures of [K(1-aza-18-crown-6)]BH(4) and its 18-crown-6 analogue
      exhibits significantly different primary and secondary stabilizing interactions.
      However, their respective ion pairs display similar cation-to-anion interactions,
      in spite of the differences in the nature of the crown ether ligand.

PMID- 21713293
TI  - A survey on the temporal and spatial distribution of perchlorate in the Potomac
      River.
AB  - Samples of river water and treated drinking water were obtained from eight sites
      along the Potomac River between western Maryland and Washington DC. Samples were
      collected each month from October 2007 to September 2008 and analyzed for
      perchlorate by ion chromatography/mass spectrometry. Data on anions were also
      collected for seven of the twelve months. Data were analyzed to identify spatial
      and temporal patterns for the occurrence of perchlorate in the Potomac. Over the
      year of sampling, the largest monthly increase occurred from June to July, with
      levels then decreasing from July to September. Samples from the period between
      December and May had lower perchlorate concentrations, relative to the remainder
      of the study year. Spatially, higher levels of perchlorate were found at sites
      located in west-central Maryland, the eastern panhandle of West Virginia, and
      central northern Virginia, with levels decreasing slightly as the Potomac
      approaches Washington DC. Within the sampling boundaries, river (untreated) water
      perchlorate concentrations ranged from 0.03 MUg L(-1) to 7.63 MUg L(-1), averaged
      0.67 +/- 0.97 MUg L(-1) over the year-long period and had a median value of 0.37
      MUg L(-1). There was no evidence that any of the existing drinking water
      treatment technologies at the sampling sites were effective in removing
      perchlorate. There were no correlations found between the presence of perchlorate
      and any of the anions or water quality parameters examined in the source water
      with the exception of a weak positive correlation with water temperature. Results
      from the summer (June-August) and fall (September-November) months sampled in
      this study were generally higher than from the winter and spring months (December
      May). All but one of the locations had annual average perchlorate levels below 1
      MUg L(-1); however, 7 of the 8 sites sampled had river water perchlorate
      detections over 1 MUg L(-1) and 5 of the 8 sites had treated water detections
      over this level.

PMID- 21713294
TI  - Direct conversion of acetals to esters with high regioselectivity via O,P
      acetals.
AB  - A new direct conversion of O,O-acetals to esters via O,P-acetal intermediates was
      developed. The regioselective cleavage of unsymmetrical cyclic acetals occurred
      to give the more crowded esters as single isomers.

PMID- 21713295
TI  - Synthesis and assembling properties of bioorganometallic cyclometalated Au(III)
      alkynyls bearing guanosine moieties.
AB  - A guanosine-based Au(III) compound was demonstrated to serve as a versatile
      bioorganometallic conjugate, which could form a variety of aggregates in the
      absence and presence of KPF(6)via self-assembly of the guanosine moiety.

PMID- 21713296
TI  - Porpholactams and chlorolactams: replacement of a beta,beta'-double bond in meso
      tetraphenyl-porphyrin and -chlorin by a lactam moiety.
AB  - Reaction of meso-tetraphenylporpholactone with hydrazine converts the lactone
      moiety to an N-aminolactam. It also reduces the opposite pyrrolic moiety of both
      the starting material and the N-aminolactam, generating chlorin-like
      chlorolactone and N-aminochlorolactam, respectively. Reductive N-N cleavage of
      the N-aminoporpholactam generates the parent porpholactam.

PMID- 21713297
TI  - Fullerenolates: metallated polyhydroxylated fullerenes with potent anti-amyloid
      activity.
AB  - It has been revealed for the first time that sodium fullerenolate
      Na(4)[C(60)(OH)(~30)] (NaFL), a water soluble polyhydroxylated [60]fullerene
      derivative, destroys amyloid fibrils of the Abeta(1-42) peptide in the brain and
      prevents their formation in in vitro experiments. The cytotoxicity of NaFL was
      found to be negligibly low with respect to nine different culture cell lines. At
      the same time, NaFL showed a very low acute toxicity in vivo. The maximal
      tolerable dose (MTD) and LD50 for NaFL correspond to 1000 mg kg(-1) and 1800 mg
      kg(-1), respectively, as revealed by in vivo tests in mice using intraperitoneal
      drug injection. The observed pronounced anti-amyloid activity and low toxicity of
      NaFL make it a very promising lead drug for the development of potent fullerene
      based therapeutic approaches for the treatment of amyloidoses, such as
      Alzheimer's disease and others.

PMID- 21713298
TI  - HIV infection and cardiovascular risk in black South Africans.

PMID- 21713299
TI  - Cardiovascular disease prevention in women: are we up to date?

PMID- 21713300
TI  - The history of the Pan-African Society of Cardiology (PASCAR): the first 30
      years, 1981-2011.
AB  - The year 2011 marks the 30th anniversary of the founding of the Pan-African
      Society of Cardiology (PASCAR). Throughout its brief history, PASCAR has been
      integral to improving the cardiovascular health of the people of Africa. During
      the past three decades, many African countries have been vulnerable to political
      and social turmoil, and PASCAR itself has been repeatedly challenged to press on
      with its mission, in spite of innumerable practical obstacles. This article
      celebrates the hard work and dedication of PASCAR's founders and subsequent
      leaders, and challenges the present and future generations to carry on the charge
      of furthering the health of Africans.

PMID- 21713301
TI  - Relationship between Tei index of myocardial performance and left ventricular
      geometry in Nigerians with systemic hypertension.
AB  - INTRODUCTION: Left ventricular geometry is associated with cardiovascular events
      and prognosis. The Tei index of myocardial performance is a combined index of
      systolic and diastolic dysfunction and has been shown to be a predictor of
      cardiovascular outcome in heart diseases. The relationship between the Tei index
      and left ventricular geometry has not been well studied. This study examined the
      association between the Tei index and left ventricular geometry among
      hypertensive Nigerian subjects. METHODS: We performed echocardiography on 164
      hypertensives and 64 control subjects. They were grouped into four geometric
      patterns based on left ventricular mass and relative wall thickness. The Tei
      index was obtained from the summation of the isovolumic relaxation time and the
      isovolumic contraction time, divided by the ejection time. Statistical analysis
      was done using SPSS 16.0. RESULTS: Among the hypertensive subjects, 68 (41.4%)
      had concentric hypertrophy, 43 (26.2%) had concentric remodelling, 24 (14.6%) had
      eccentric hypertrophy, and 29 (17.7%) had normal geometry. The Tei index was
      significantly higher among the hypertensives with concentric hypertrophy (CH),
      concentric remodelling (CR) and eccentric hypertrophy (EH) compared to the
      hypertensives with normal geometry (0.83 +/- 1.0, 0.71 +/- 0.2, 0.80 +/- 0.2 vs
      0.61 +/- 0.2, respectively). The Tei index was higher among hypertensives with CH
      and EH than those with CR. Stepwise regression analysis showed that the Tei index
      was related to ejection fraction, fractional shortening and mitral E/A ratio.
      CONCLUSION: Among Nigerian hypertensives, LV systolic and diastolic functions
      (using the Tei index) were impaired in all subgroups of hypertensive patients
      according to their left ventricle geometry compared to the control group. This
      impairment was more advanced in patients with concentric and eccentric
      hypertrophy.

PMID- 21713302
TI  - Is HIV-1 infection associated with endothelial dysfunction in a population of
      African ancestry in South Africa?
AB  - The chronic infection status suffered by HIV-infected individuals promotes
      chronic arterial inflammation and injury, which leads to dysfunction of the
      endothelium, atherosclerosis and thrombosis. Although HIV-1 subtype C is
      prevalent in South Africa and accounts for almost a third of the infections
      worldwide, this subtype differs genetically from HIV-1 subtype B on which the
      majority of studies have been done. The objective of this study was to assess
      whether newly identified, never-treated, HIV-1-infected South African
      participants showed signs of endothelial dysfunction, accelerated atherosclerosis
      and increased blood coagulation. We compared 300 newly diagnosed (never
      antiretroviraltreated) HIV-infected participants to 300 age-, gender-, body mass
      index- and locality-matched uninfected controls. Levels of high-density
      lipoprotein cholesterol (HDL-C), triglycerides, interleukin-6 (IL-6), C-reactive
      protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule-1 (VCAM-1), fibrinogen and plasminogen activator inhibitor-1 (PAI-1),
      and carotid radialis pulse wave velocity (cr-PWV) were determined. The HIV
      infected participants showed lower HDL-C and higher IL-6, CRP, ICAM-1 and VCAM-1
      levels compared to the uninfected controls. No differences in fibrinogen and PAI
      1 levels were detected. A continuous positive trend of increasing age with cr-PWV
      was detected in the HIV-infected group. Our findings suggest inflammatory injury
      of the endothelium, pointing to endothelial dysfunction of never-treated HIV-1
      infected South Africans of African ancestry. Although no indication of a
      prothrombotic state could be detected, there was an indication of accelerated
      vascular aging and probable early atherosclerosis in the older HIV-infected
      participants.

PMID- 21713303
TI  - The metabolic syndrome, anthropometry and microalbumin.

PMID- 21713304
TI  - Aberrant pathway in an anomaly: pre-excitation syndrome in association with
      coronary sinus aneurysm.
AB  - Congenital coronary sinus anomalies are unusual and they rarely coexist with
      accessory atrio-ventricular pathways. These anomalies are generally symptomatic;
      however they can cause difficulty in mapping. The association between accessory
      pathway and coronary sinus anomalies may suggest an embryological link. Here, we
      report on a male patient with an accessory conducting pathway in the coronary
      sinus, leading to Wolff-Parkinson-White (WPW) syndrome.

PMID- 21713305
TI  - Mycotic pseudoaneurysm of the ascending aorta following purulent pericardial
      effusion diagnosed by multi-slice computed tomography.
AB  - Mycotic pseudoaneurysm of the aorta is an uncommon disease, especially in
      childhood but has a high mortality due to spontaneous rupture. It is caused by
      endarteritis following bacteraemia or fungaemia. Due to spontaneous rupture,
      early diagnosis is very important.

PMID- 21713307
TI  - The management of tobacco smoking.

PMID- 21713308
TI  - Serving diabetes and cardiology: round three of the South African
      diabetologist/cardiologist debate.

PMID- 21713306
TI  - Once fat was fat and that was that: our changing perspectives on adipose tissue.
AB  - Past civilisations saw excess body fat as a symbol of wealth and prosperity as
      the general population struggled with food shortages and famine. Nowadays it is
      recognised that obesity is associated with co-morbidities such as cardiovascular
      disease and diabetes. Our views on the roll of adipose tissue have also changed,
      from being solely a passive energy store, to an important endocrine organ that
      modulates metabolism, immunity and satiety. The relationship between increased
      visceral adiposity and obesity-related co-morbidities has lead to the recognition
      that variation in fat distribution contributes to ethnic differences in the
      prevalence of obesity-related diseases. Our current negative view of adipose
      tissue may change with the use of pluripotent adipose-derived stromal cells,
      which may lead to future autologous stem cell therapies for bone, muscle, cardiac
      and cartilage disorders. Here, we briefly review the concepts that adipose tissue
      is an endocrine organ, that differences in body fat distribution underline the
      aetiology of obesity-related co-morbidities, and the use of adipose-derived stem
      cells for future therapies.

PMID- 21713309
TI  - Re-LY trial: new sub-analyses highlight stroke reduction in all types of non
      valvular atrial fibrillation.

PMID- 21713310
TI  - New telmisartan/amlodipine single-pill combination offers both efficacy and
      tolerability.

PMID- 21713311
TI  - Prasugrel study addresses timing of thienopyridine loading dose in NSTEMI
      patients pre-PCI (the ACCOAST study).

PMID- 21713313
TI  - Computational intelligence in early diabetes diagnosis: a review.
AB  - The development of an effective diabetes diagnosis system by taking advantage of
      computational intelligence is regarded as a primary goal nowadays. Many
      approaches based on artificial network and machine learning algorithms have been
      developed and tested against diabetes datasets, which were mostly related to
      individuals of Pima Indian origin. Yet, despite high accuracies of up to 99% in
      predicting the correct diabetes diagnosis, none of these approaches have reached
      clinical application so far. One reason for this failure may be that
      diabetologists or clinical investigators are sparsely informed about, or trained
      in the use of, computational diagnosis tools. Therefore, this article aims at
      sketching out an outline of the wide range of options, recent developments, and
      potentials in machine learning algorithms as diabetes diagnosis tools. One focus
      is on supervised and unsupervised methods, which have made significant impacts in
      the detection and diagnosis of diabetes at primary and advanced stages.
      Particular attention is paid to algorithms that show promise in improving
      diabetes diagnosis. A key advance has been the development of a more in-depth
      understanding and theoretical analysis of critical issues related to algorithmic
      construction and learning theory. These include trade-offs for maximizing
      generalization performance, use of physically realistic constraints, and
      incorporation of prior knowledge and uncertainty. The review presents and
      explains the most accurate algorithms, and discusses advantages and pitfalls of
      methodologies. This should provide a good resource for researchers from all
      backgrounds interested in computational intelligence-based diabetes diagnosis
      methods, and allows them to extend their knowledge into this kind of research.

PMID- 21713314
TI  - Zinc and zinc transporter regulation in pancreatic islets and the potential role
      of zinc in islet transplantation.
AB  - The critical trace element zinc is essential for normal insulin production, and
      plays a central role in cellular protection against apoptosis and oxidative
      stress. The regulation of zinc within the pancreas and beta-cells is controlled
      by the zinc transporter families ZnT and ZIP. Pancreatic islets display wide
      variability in the occurrence of these molecules. The zinc transporter, ZnT8 is
      an important target for autoimmunity in type 1 diabetes. Gene polymorphisms of
      this transporter confer sensitivity for immunosuppressive drugs used in islet
      transplantation. Understanding the biology of zinc transport within pancreatic
      islets will provide insight into the mechanisms of beta-cell death, and may well
      reveal new pathways for improvement of diabetes therapy, including islet
      transplantation. This review discusses the possible roles of zinc in beta-cell
      physiology with a special focus on islet transplantation.

PMID- 21713315
TI  - Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated
      with coronary artery disease in patients with diabetic nephropathy.
AB  - BACKGROUND: Indoxyl sulphate (IS) and p-cresylsulphate (PCS) are uremic toxins
      with similar protein-binding, dialytic clearance, and proinflammatory features.
      Few studies have evaluated the possible associations between these solutes and
      coronary artery disease (CAD) in type 2 diabetes (T2D) patients. METHODS: A
      hospital-based case control study was performed. A total of 209 T2D patients were
      divided into two groups based on the presence/absence of significant CAD (>=50%
      luminal reduction). Serum total PCS and IS levels were measured using the Ultra
      Performance LC System. The relationship between total PCS and IS levels were
      investigated. Coronary calcium scores and the modified Gensini score were
      analyzed. RESULTS: Serum total PCS and IS levels were significantly higher in
      patients with both T2D and significant CAD, than in non-diabetic control subjects
      and T2D patients without CAD (all p < 0.05). Logistic regression analysis
      revealed independent and significant associations between the two solutes and CAD
      status. Serum total PCS, IS, and numbers of diseased vessels were elevated in
      groups with estimated glomerular filtration rate (eGFR) of 60-89 ml/min/1.73 m2
      and below. Also, serum total PCS and IS levels were significantly associated with
      eGFR, coronary calcium scores, Gensini score, adipocytokines (adiponectin,
      visfatin, and leptin), and total white blood cell count. CONCLUSIONS: Serum total
      PCS and IS levels were elevated in patients with T2D and CAD. These increases
      were associated with renal function deterioration, inflammation, and coronary
      atherosclerosis.

PMID- 21713316
TI  - A WFS1 haplotype consisting of the minor alleles of rs752854, rs10010131, and
      rs734312 shows a protective role against type 2 diabetes in Russian patients.
AB  - BACKGROUND: Rare variants of the WFS1 gene encoding wolframin cause Wolfram
      syndrome, a monogenic disease associated with diabetes insipidus, diabetes
      mellitus, optic atrophy, and deafness. In contrast, common variants of WFS1
      showed association with type 2 diabetes (T2D) in numerous Caucasian populations.
      AIM: In this study, we tested whether the markers rs752854, rs10010131, and
      rs734312, located in the WFS1 gene, are related to the development of T2D in a
      Russian population. METHODS: The polymorphic markers were genotyped in Russian
      diabetic (n = 1,112) and non-diabetic (n = 1,097) patients using a Taqman allele
      discrimination assay. The correlation between the carriage of disease-associated
      WFS1 variants and the patients' clinical and metabolic characteristics was
      studied using ANOVA and ANCOVA. Adjustment for confounding variables such as
      gender, age, body mass index, obesity, HbA1c, and hypertension was made. RESULTS:
      Haplotype GAG, consisting of the minor alleles of rs752854, rs10010131, and
      rs734312, respectively, showed association with decreased risk of T2D (OR = 0.44,
      95% CI = 0.32-0.61, p = 4.3 x 10(-7)). Compared to other WFS1 variants, non
      diabetic individuals homozygous for GAG/CAG had significantly increased fasting
      insulin (p(adjusted) = 0.047) and homeostasis model assessment of beta-cell
      function (HOMA-beta) index (p(adjusted) = 0.006). Diabetic patients homozygous
      for GAG/GAG showed significantly elevated levels of 2-h insulin (p(adjusted) =
      0.029) and HOMA-beta = 0.011. CONCLUSIONS: Disease-associated variants of WFS1
      contribute to the pathogenesis of T2D through impaired insulin response to
      glucose stimulation and altered beta-cell function.

PMID- 21713317
TI  - Prevalence of undiagnosed diabetes and quality of care in diabetic patients
      followed at primary and tertiary clinics in Abu Dhabi, United Arab Emirates.
AB  - AIMS: To investigate the prevalence of undiagnosed type 2 diabetes (T2D) at
      primary health care (PHC) clinics, and to assess the quality of care of diabetic
      patients followed at a tertiary hospital diabetes center in Abu Dhabi, United
      Arab Emirates (UAE). METHODS: Between May 2009 and October 2010, adult patients
      attending two PHC clinics, and adult diabetic patients attending the diabetes
      center, were invited to participate in the study. After overnight fast,
      participants returned for interview and laboratory tests. Undiagnosed T2D was
      defined by FPG >= 7.0 mmol/l or HbA1c >= 6.5%. Quality of care was assessed by
      reported care practices and achievement of internationally recognized targets.
      RESULTS: Out of 239 patients at PHC clinics without history of T2D, 14.6% had
      undiagnosed T2D, and 31% had increased risk of diabetes (FPG 5.6-7.0 mmol/l or
      HbA1c 5.7-6.5%). The independent predictors of undiagnosed T2D were age (adjusted
      OR per year 1.07, 95% CI 1.04-1.11, p < 0.001) and BMI >= 25 (adjusted OR 4.2,
      95% CI 0.91-19.7, p = 0.033). Amongst all 275 diagnosed T2D patients, including
      those attending PHC clinics and those followed at the diabetes center, it was
      found that 40.1% followed dietary recommendations, 12% reported visiting a
      diabetes educator, 28.2% walked for exercise, and 13.5% attained recognized
      targets of HbA1c < 7%, blood pressure < 130/80 mmHg, and LDL cholesterol < 2.6
      mmol/l. CONCLUSIONS: Almost half of the adult patients attending PHC clinics had
      undiagnosed T2D, or increased diabetes risk. Care practices, and achievement of
      treatment targets, were suboptimal.

PMID- 21713318
TI  - Role of vitamin K-dependent proteins in the arterial vessel wall.
AB  - Vitamin K was discovered early last century at the same time as the vitamin K
      antagonists. For many years the role of vitamin K was solely ascribed to
      coagulation and coagulation was thought to be involved only at the venous blood
      side. This view has dramatically changed with the discovery of vitamin K
      dependent proteins outside the coagulation cascade and the role of coagulation
      factors at the arterial side. Vitamin K-dependent proteins are involved in the
      regulation of vascular smooth muscle cell migration, apoptosis, and
      calcification. Vascular calcification has become an important independent
      predictor of cardiovascular disease. Vitamin K-antagonists induce inactivity of
      inhibitors of vascular calcification, leading to accelerated calcification. The
      involvement of vitamin K-dependent proteins such as MGP in vascular calcification
      make that calcification is amendable for intervention with high intake of vitamin
      K. This review focuses on the effect of vitamin K-dependent proteins in vascular
      disease.

PMID- 21713319
TI  - Involvement of microparticles in diabetic vascular complications.
AB  - Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and
      vascular complications. Circulating microparticles (MPs) are involved in
      thrombosis, inflammation, and angiogenesis. However, the role of MPs in T2DM
      vascular complications is unclear. We characterised the cell origin and pro
      coagulant profiles of MPs obtained from 41 healthy controls and 123 T2DM patients
      with coronary artery disease, retinopathy and foot ulcers. The effects of MPs on
      endothelial cell coagulability and tube formation were evaluated. Patients with
      severe diabetic foot ulcers expressed the highest levels of MPs originated from
      platelet and endothelial cells and negatively-charged phospholipid-bearing MPs.
      MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor
      (TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients
      (<0.7) but high in patients with coronary artery disease and foot ulcers (>1.8,
      p>=0.002). MPs of all T2DM patients induced a more than two-fold increase in
      endothelial cell TF (antigen and gene expression) but did not affect TFPI levels.
      Tube networks were longest and most stable in endothelial cells that were
      incubated with MPs of healthy controls, whereas no tube formation occurred in MPs
      of diabetic patients with coronary artery disease. MPs of diabetic retinopathy
      and diabetic foot ulcer patients induced branched tube networks that were
      unstable and collapsed over time. This study demonstrates that MP characteristics
      are related to the specific type of vascular complications and may serve as a bio
      marker for the pro- coagulant state and vascular pathology in patients with T2DM.

PMID- 21713320
TI  - The relationship between platelet reactivity and infarct-related artery patency
      in patients presenting with a ST-elevation myocardial infarction.
AB  - Both heightened platelet reactivity and an occluded infarct related artery (IRA)
      on initial angiography and at the time of primary percutaneous coronary
      intervention (PCI) are associated with a worsened clinical outcome in patients
      with ST-elevation myocardial infarction (STEMI). However, the relationship
      between platelet reactivity and IRA patency has not yet been established.
      Consecutive STEMI-patients were enrolled in this study. Patients who had TIMI
      flow (thrombolysis in myocardial infarction) 0 or 1 on initial angiography
      constituted the occluded IRA group and patients having TIMI-flow 2 or 3 comprised
      the IRA patent group. Platelet function measurements were performed using the PFA
      100 COL/ADP cartridge and light transmittance aggregometry without agonist
      (spontaneous) and after stimulation with adenosine diphosphate (ADP) and
      arachidonic acid (AA). Ninety-nine patients were enrolled, of whom 49 presented
      with an occluded IRA. Multivariate analysis identified the following independent
      factors to be associated with an occluded IRA; short COL/ADP closure time (ORper
      quartile increase=0.60; 95% CI, 0.39-.93; p=0.02), the 20 MUM ADP-induced light
      transmittance aggregometry (ORper quartile increase =1.77; 95% CI, 1.15-2.73;
      p=0.01) and leukocyte counts (odds ratio [OR]=1.21; 95% CI, 1.05-1.39; p =
      0.008). In conclusion, heightened platelet reactivity and elevated leukocyte
      counts are associated with an occluded IRA upon presentation in STEMI-patients.
      These results emphasise the importance of potent antithrombotic therapy early
      after the onset of symptoms, to obtain early recanalisation of the IRA.

PMID- 21713321
TI  - The effect of decitabine on megakaryocyte maturation and platelet release.
AB  - Thrombocytopenia is a common feature of myelodysplastic syndromes (MDS). 5-aza-2'
      deoxycytidine (decitabine) has been used to treat MDS with an approximately 20%
      response rate in thrombocytopenia. However, the mechanism of how decitabine
      increases platelet count is not clear. In this study, we investigated the effect
      of decitabine on megakaryocyte maturation and platelet release in the mouse. The
      effect of decitabine on megakaryocyte maturation was studied in an in vitro
      megakaryocyte differentiation model utilising mouse bone marrow cells and mouse
      megakaryoblastic cell line L8057. Decitabine (2.5 MUM) is able to induce L8057
      cells to differentiate into a megakaryocyte-like polyploidy cells with positive
      markers of acetylcholinesterase and alphaIIb integrin (CD41). Higher expression
      of alphaIIb integrin was also found in primary mouse bone marrow cells and human
      cord blood CD34+ cells cultured with both thrombopoietin and decitabine as
      compared to thrombopoietin alone. In addition, we noted a 30% platelet count
      increase in Balb/c mice 12 hours after the injection of decitabine at a
      clinically relevant dose (15 mg/m2), suggesting a rapid platelet release from the
      spleen or bone marrow. Our data suggest that decitabine increases platelet counts
      by enhancing platelet release and megakaryocyte maturation.

PMID- 21713322
TI  - Symptomatic and incidental thromboembolism are both associated with mortality in
      pancreatic cancer.
AB  - Pancreatic cancer is known to be associated with VTE, but contemporary rates of
      incidental and symptomatic VTE events and their association with mortality are
      incompletely understood. We conducted a retrospective cohort study of consecutive
      pancreatic adenocarcinoma patients at the University of Rochester from 2006-2009.
      Data were analysed using a Cox model with time-dependent covariates. A total of
      1,151 radiologic exams of 135 patients were included. Forty-seven patients
      (34.8%) experienced VTE including 12 pulmonary emboli (PE), 28 deep-vein
      thromboses (DVTs) and 47 visceral vein events. Incidental events comprised 33.3%
      of PEs, 21.4% of DVTs and 100% of visceral VTE. Median (95% CI) conditional
      survival beyond three months was 233 (162-322) more days for those without VTE,
      which was significantly greater than 12 (3-60) days for those with DVT as first
      event (p<0.0001) and 87 (14-322) days with visceral first events (p=0.022). In
      multivariate analysis, DVT (HR 25, 95% CI 10-63, p <0.0001), PE (HR 8.9, 95% CI
      2.5-31.7, p = 0.007) and incidental visceral events (HR 2.6, 95% CI 1.6-4.2, p
      =0.0001) were all associated with mortality, though anticoagulants reduced these
      risks by 70% (26-88%, p = 0.009). In conclusion, VTE occurs in over one-third of
      contemporary pancreatic cancer patients and, whether symptomatic or incidental,
      is strongly associated with worsened mortality. The role of anticoagulation in
      treating incidental or visceral VTE warrants further study.

PMID- 21713323
TI  - Venous thromboembolism in pregnant and puerperal women in Denmark 1995-2005. A
      national cohort study.
AB  - Venous thromboembolism (VTE) is the leading cause of maternal death in the
      Western world, and the risk increases during pregnancy and puerperal period. It
      was the objective of the present study to estimate the absolute and the relative
      risk of VTE at different weeks of gestation and in the postnatal period as
      compared to non-pregnant women. This was a historical controlled national cohort
      study. The National Registry of Patients identified relevant diagnoses. These
      data were linked to The National Registry of Medical Products Statistics for
      information about current use of oral contraceptives. Danish women 15 to 49 years
      old during the period January 1995 through December 2005 were included in the
      study. In total 819,751 pregnant women were identified of whom 727 had a
      diagnosis of VTE. The absolute risk of VTE per 10,000 pregnancy-years increased
      from 4.1 (95% CI, 3.2 to 5.2) during week 1-11 up to 59.0 (95% CI: 46.1 to 76.4)
      in week 40 and decreased in the puerperal period from 60.0 (95% CI:47.2-76.4)
      during the first week after birth to 2.1 (95% CI:1.1 to 4.2) during week 9-12
      after birth. Compared with non-pregnant women, the incidence rate ratio rose from
      1.5 (95% CI:1.1 to 1.9) in week 1-11, to 21.0 (95%CI16.7 to 27.4) in week 40 and
      21.5 (95% CI:16.8 to 27.6) in the first week after delivery, declining to 3.8
      (95% CI:2.5 to 5.8) 5-6 weeks after delivery. In conclusion, the risk of VTE
      increases almost exponentially through pregnancy and reaches maximum just after
      delivery and is no longer significantly increased six weeks after delivery.

PMID- 21713324
TI  - Decreased proteinZ levels in patients with rheumatoid arthritis: links with
      inflammation.

PMID- 21713325
TI  - The inhibition effect of anti-GPIIIa49-66 antibody on megakaryocyte
      differentiation.
AB  - We previously reported that patients with early-onset HIV-1 ITP developed a
      unique anti-platelet integrin GPIIIa antibody against the GPIIIa49-66 epitope.
      Anti-GPIIIa49-66 antibody-induced platelet fragmentation requires sequential
      activation of the platelet 12-lipoxygenase (12-LO) and NADPH oxidase to release
      reactive oxygen species (ROS). 12-LO is upstream of the NADPH oxidase pathway and
      12(S)-HETE, the product of 12-LO, induces the same oxidative platelet
      fragmentation as anti-GPIIIa49-66. Since the megakaryocyte (MK) is the progenitor
      cell for platelets, we have investigated the effect of anti-GPIIIa49-66 on MK
      differentiation and, in particular, the potential role of anti-GPIIIa49-66
      induced ROS in this process. We first show that polyclonal anti-GPIIIa49-66
      antibody isolated from HIV-1 ITP patients inhibits MK proliferation 2.5-fold in
      in vitro culture of human cord blood CD34+ cells driven by thrombopoietin (TPO).
      We also observe a three-fold decrease in the number of MK colony-forming units in
      the presence of a human monoclonal anti-GPIIIa49-66 antibody. However, we could
      not detect ROS release in DCFH-loaded mouse megakaryoblastic cells L8057 treated
      with anti-GPIIIa49-66 antibody. In addition, 12(S)-HETE does not inhibit the in
      vitro differentiation of L8057 cells induced by TPO. In fact, we found a dose
      dependent increase in the percentage of CD41 positive cells (from 17.1% to 48.7%)
      in in vitro culture of L8057 cells treated with various concentrations of H2O2
      (from 5 to 20 MUM). We therefore conclude that the anti-GPIIIa49-66 antibody
      inhibits MK differentiation through beta3 integrin signalling independent of ROS
      release.

PMID- 21713326
TI  - Clopidogrel response variability and the advent of personalised antiplatelet
      therapy. A bench to bedside journey.
AB  - Platelet-mediated thrombosis is a dreaded clinical event and is the primary cause
      of acute coronary syndromes and post-percutaneous intervention (PCI) ischaemic
      events. There has been a long standing interest in the ex vivo quantification of
      platelet reactivity to assess the risk of thrombosis. Early studies demonstrated
      platelet activation and heightened platelet reactivity in acute coronary
      syndromes and after PCI. However, a demonstration that heightened reactivity
      actually precipitated the ischaemic event was lacking. Our knowledge of platelet
      receptor physiology and the advent of novel inhibitors have significantly
      advanced the field. The P2Y12 receptor has been shown to play a pivotal role in
      the amplification of platelet activation by multiple agonists and its inhibition
      has resulted in improved clinical outcomes. The most widely used drug to block
      P2Y12 receptor, clopidogrel is associated with resistance in selected patients
      and these patients have been shown to be at increased risk for post-PCI ischaemic
      event occurrence in multiple studies. Importantly, a threshold of high platelet
      reactivity has been demonstrated, and beyond this threshold ischaemic events
      occur precipitously. Based on the current evidence, it is rational to quantify
      the intensity of the ADP-P2Y12 interaction in the patient at the greatest risk
      for thrombosis-the PCI patient. However, there is only evidence from small
      clinical trials demonstrating the clinical efficacy of changing an antiplatelet
      regimen based on an ex vivo platelet function measurement. Moreover, there are
      numerous patients with vulnerable coronary anatomy that have not yet experienced
      plaque rupture; the prognostic role of a measurement of platelet reactivity in
      the latter group has never been studied. Large-scale trials are ongoing that will
      investigate the role of personalised antiplatelet therapy in the PCI patient.

PMID- 21713327
TI  - Intrinsic platelet reactivity before P2Y12 blockade contributes to residual
      platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose
      clopidogrel. Results from PRINCIPLE-TIMI 44.
AB  - It was the objective of this study to determine whether the intrinsic platelet
      response to adenosine diphosphate (ADP) before thienopyridine exposure
      contributes to residual platelet reactivity to ADP despite high level P2Y12
      blockade by prasugrel (60 mg loading dose [LD]), 10 mg daily maintenance dose
      [MD]) or high-dose clopidogrel (600 mg LD, 150 mg daily MD). High residual
      platelet function during clopidogrel therapy is associated with poor clinical
      outcomes. It remains unknown whether the relationship between platelet reactivity
      prior to treatment with clopidogrel (300 mg LD, 75 mg daily MD) and residual on
      treatment platelet reactivity is maintained after more potent P2Y12 inhibition.
      PRINCIPLE-TIMI 44 was a randomised, double-blind, two-phase crossover study of
      prasugrel compared with high-dose clopidogrel in 201 patients undergoing cardiac
      catheterisation for planned percutaneous coronary intervention. ADP-stimulated
      platelet-monocyte aggregates, platelet surface P-selectin and platelet
      aggregation were measured pre-treatment, during LD (6 h and 18-24 h) and MD (15
      d). Correlations of pre-treatment to on-treatment values were determined by
      Spearman rank order. Prasugrel resulted in greater platelet inhibition than high
      dose clopidogrel for each measure. However, for both drugs, pre-treatment
      reactivity to ADP predicted 6 h, 18-24 h and 15 day reactivity to ADP
      (correlations 0.24-0.62 for platelet-monocyte aggregates and P-selectin). In
      conclusion, a patient's intrinsic platelet response to ADP before exposure to
      thienopyridines contributes to residual platelet reactivity to ADP despite high
      level P2Y12 blockade with high-dose clopidogrel or even higher level P2Y12
      blockade with prasugrel. Patients who are hyper-responsive to ADP pre-treatment
      are more likely to be hyper-responsive to ADP on-treatment, which may be relevant
      to therapeutic strategies.

PMID- 21713328
TI  - A comparison of the original and simplified Pulmonary Embolism Severity Index.
AB  - The Pulmonary Embolism Severity Index (PESI) is a validated clinical prognostic
      model for patients with pulmonary embolism (PE). Recently, a simplified version
      of the PESI was developed. We sought to compare the prognostic performance of the
      original and simplified PESI. Using data from 15,531 patients with PE, we
      compared the proportions of patients classified as low versus higher risk between
      the original and simplified PESI and estimated 30-day mortality within each risk
      group. To assess the models' accuracy to predict mortality, we calculated
      sensitivity, specificity, and predictive values and likelihood ratios for low-
      versus higher-risk patients. We also compared the models' discriminative power by
      calculating the area under the receiver-operating characteristic curve. The
      overall 30-day mortality was 9.3%. The original PESI classified a significantly
      greater proportion of patients as low-risk than the simplified PESI (40.9% vs.
      36.8%; p<0.001). Low-risk patients based on the original and simplified PESI had
      a mortality of 2.3% and 2.7%, respectively. The original and simplified PESI had
      similar sensitivities (90% vs. 89%), negative predictive values (98% vs. 97%),
      and negative likelihood ratios (0.23 vs. 0.28) for predicting mortality. The
      original PESI had a significantly greater discriminatory power than the
      simplified PESI (area under the ROC curve 0.78 [95% CI: 0.77-0.79] vs. 0.72 [95%
      CI: 0.71-0.74]; p<0.001). In conclusion, even though the simplified PESI
      accurately identified patients at low-risk of adverse outcomes, the original PESI
      classified a higher proportion of patients as low-risk and had a greater
      discriminatory power than the simplified PESI.

PMID- 21713329
TI  - Novel fibrinogen (B beta401Gly->Val) presents as dys- or hypodysfibrinogenaemia
      due to alterations in sialic acid content.

PMID- 21713330
TI  - Trachoma in Latin America: an opportunity for elimination.

PMID- 21713331
TI  - [Eaton-Lambert myasthenic syndrome].

PMID- 21713332
TI  - Cutaneous tuberculosis after mesotherapy: report of six cases.
AB  - INTRODUCTION: Cutaneous tuberculosis as a result of a needle injection is a rare
      event; it generally occurs among medical and laboratory personnel and among
      patients receiving percutaneous treatment. OBJECTIVE: Six patients are presented
      who developed cutaneous tuberculosis after mesotherapy cosmetic treatment.
      MATERIAL AND METHODS: One to four months after injection of an unknown product as
      treatment for obesity and cellulites, five women and a man developed papules,
      nodules and drainage of wax like material at the inoculated sites; this was
      interpreted clinically as a non tuberculous mycobacterium infection. Skin
      biopsies were taken for a histopathologic study; the biopsy and exudates were
      cultured to make a phenotypic identification. Polymerase chain reaction and
      restriction enzyme pattern analyses (PCR-restriction pattern analysis))
      procedures were applied to the skin biopsies. RESULTS: Mycobacterium tuberculosis
      was confirmed in the culture and by PRA analysis in the paraffin-embedded
      biopsies. The patients had never had tuberculosis. Their thoracic X rays were
      normal and the size of the tuberculin reaction was 17 to 20 mm. Five patients
      recovered with antituberculosis treatment and the sixth spontaneously healed
      after the removal of the largest cutaneous module. No satellite adenopathy or
      recurrences were observed. CONCLUSIONS: A previously undescribed mode of
      acquisition cutaneous tuberculosis was described. This was the second incident of
      a demonstrated cutaneous tuberculosis following mesotherapy in Colombia. Skin
      lesions induced by injections must be tested to detect mycobacterias to include
      M. tuberculosis.

PMID- 21713333
TI  - Endophthalmitis by Pseudomonas aeruginosa. after penetrating keratoplasty, case
      report with an epidemiological investigation.
AB  - INTRODUCTION: An endophthalmitis following penetrating keratoplasty by
      Pseudomonas aeruginosa is a devasting case with very poor visual outcomes.
      OBJECTIVE: To determine the origin of an infection after a penetrating
      keratoplasty. MATERIALS AND METHODS: After an endophthalmitis an epidemiological
      study was undertaken with the approval of the ethics committee and support of a
      medical team comprised of an epidemiologist, infectologist, bacteriologist and
      ophthalmologists specializing in cornea. Factors that may have contributed to the
      risk of infection were assessed, for example, the processing and preservation of
      the cornea in the moment of the extraction, the characteristics of the donor,
      recipient and infecting bacterium, as well as the details pertaining to the
      surgical operation. RESULTS: No risks factors were found in the institution, in
      the eye bank facilities, in the donor or in the receptor. However, sterile
      technique could not be guaranteed in the morgue where the corneal extraction
      occurred, and other isolated cases of endophthalmitis post-keratoplasty had been
      documented involving tissues from the same morgue that had been processed by two
      eye banks in the same city. Characteristics of the multi-resistant Pseudomonas
      sp. demonstrated its origin from a hospital environment due to its previous
      exposure to a variety of antibiotics. CONCLUSIONS: Corneal extraction site must
      guarantee an antiseptic preparation and aseptic tissue donor recuperation;
      although in this study it was not feasible to accurately establish the infection
      source, all of the findings led to suspect a possible contamination at the
      morgue.

PMID- 21713334
TI  - Disseminated mycobacteriosis affecting a prosthetic aortic valve: first case of
      Mycobacterium peregrinum type III reported in Colombia.
AB  - Rapidly growing mycobacteria are non-tuberculous mycobacteria amply present in
      the environment. Although they are not usually pathogenic for humans, they are
      opportunistic in that they can cause disease in people with disadvantageous
      conditions or who are immunocompromised. Mycobacterium peregrinum, an
      opportunistic, rapidly growing mycobacteria, belongs to the M. fortuitum group
      and has been reported as responsible for human cases of mycobacteriosis. A case
      of M. peregrinum type III is herein reported as the first in Colombia. It
      presented as a disseminated disease involving a prosthetic aortic valve
      (endocarditis) in a seventeen-year-old girl with a well-established diagnosis of
      prosthetic aortic valve endocarditis who was referred for a surgical replacement.
      Due to a congenital heart disease (subaortic stenosis with valve insufficiency),
      she had two previous aortic valve implantation surgeries. One year after the
      second implantation, the patient presented with respiratory symptoms and weight
      lost indicative of lung tuberculosis. A chest X-ray did not show parenchymal
      compromise but several Ziehl-Neelsen stains were positive. An echocardiography
      showed a vegetation on the prosthetic aortic valve. In blood and sputum samples,
      M. peregrinum type III was identified through culture, biochemical tests and
      hsp65 gene molecular analysis (PRA). The patient underwent a valve replacement
      and received a multidrug antimycobacterial treatment. Progressive recovery ensued
      and further samples from respiratory tract and blood were negative for
      mycobacteria.

PMID- 21713335
TI  - [Clinical and microbiological profiles of anti-personnel mine injuries in the
      Medellin area of northwestern Colombia].
AB  - INTRODUCTION: The counts of antipersonnel mine injuries are increasing worldwide,
      but in Colombia, documentation of the clinical and microbiological
      characteristics of these lesions is lacking. OBJECTIVES: To determine the
      clinical and microbiological characteristics of antipersonnel mine injuries for
      patients admitted for treatment during a 2 and a half year period. MATERIALS AND
      METHODS: The medical records were reviewed for 151 patients hospitalized with
      injuries caused by antipersonnel mines. The admissions occurred between January
      1st 2003 and July 31st 2005 at a highly specialized university hospital, the
      Pablo Tobon Uribe Hospital in Medellin, Colombia. RESULTS: All patients were
      male, mean age 24 years old, and all but 8 of them military. The length of stay
      averaged 20 days and hospital mortality 4%. Multiple lesions occurred in 66.8% of
      the cases, 88.0% of the injuries affected the limbs, and amputations were
      mandated in 52.3% of patients. A total of 313 specimens were cultured--68.7% of
      cultures were positive, and 386 microorganisms were identified. The most
      prevalent bacteria in the first culture were Pseudomonas aeruginosa and
      Escherichia coli. In subsequent cultures, P. aeruginosa and Enterococcus faecalis
      appeared. Most of the patients (93.4%) received standard antibiotic therapy,
      ampicillin/sulbactam. CONCLUSIONS: The clinical and microbiological
      characteristics of patients were related to their military occupation and the
      complex injuries produced by the mines. Knowledge of these characteristics will
      permit the design of better management strategies and empirical treatments.

PMID- 21713336
TI  - [Serological, molecular and virological analyses associated with yellow fever
      surveillance in Colombia].
AB  - INTRODUCTION: Yellow fever is an immunopreventable viral hemorrhagic fever that
      causes high morbidity and mortality in tropical and sub-tropical regions. In
      Colombia, approximately 5 million persons are at risk of becoming infected with
      yellow fever virus. OBJECTIVE: The serological, molecular and virological
      analyses on the yellow fever surveillance samples were summarized in order to
      indicate the importance of appropriate and timely sampling in the process of case
      confirmation. MATERIALS AND METHODS: The survey was based on samples received at
      the Arbovirus Laboratory, Virology Group, Instituto Nacional de Salud, Bogota,
      during years 2006 to 2008. A total of 2,096 serum and tissue samples were tested
      for IgM antibodies against yellow fever by capture enzyme-linked immunosorbent
      assay, viral isolation-indirect fluorescence antibody technique, and reverse
      transcriptase-polymerase chain reaction. Positive samples were correlated with
      the clinical and epidemiological findings for their interpretation and
      confirmation. RESULTS: Of the 15 yellow fever cases confirmed in Colombia during
      2006-2008 by histopathological techniques, 82% were confirmed at the Arbovirus
      Laboratory using serologic and molecular techniques. The positive cases were
      distributed in the rainforest region and in the foothills of the eastern chain of
      the Andes mountains. CONCLUSION: The case distribution and prognosis illustrated
      the necessity of maintaining and strengthening the surveillance processes in
      those regions where the yellow fever virus is circulating. The cases must be
      recruited and diagnosed sufficiently early in order to use the above techniques
      in samples from live patients, in contrast to the histopathological procedures
      that require samples from fatal cases.

PMID- 21713337
TI  - [Methicillin-resistant Staphylococcus aureus colonization in a Colombian hospital
      intensive care unit: phenotypic and molecular characterization].
AB  - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) cause nosocomial
      and community infections. MRSA colonization in hospitals has been described as an
      important risk factor during hospitalization. OBJECTIVE: The colonization
      characteristics of MRSA was described using the tools of molecular biology.
      MATERIALS AND METHODS: Between February 2007 and February 2008, 705 patients
      entering a Colombian intensive care unit (ICU) were screened for MRSA by taking
      nasopharyngeal samples. For 683 of these patients, a weekly follow-up was
      provided after they left the ICU. The susceptibility of each S. aureus isolate
      was tested against 11 antibiotics using agar dilution methods. Sixty two percent
      (62.0%) of the MRSA isolates were characterized at genetic and molecular level
      with the detection of resistant genes, SCCmec typing using PCR and the genetic
      profile with pulsed field gel electrophoresis (PFGE). RESULTS: Of the 705
      patients screened at entry to the ICU, 182 (25.8%) were colonized by S. aureus,
      and of these, 51 (7.2%) were MRSA. Of the 683 patients with follow-up, 62 (9.1%)
      were infected by MRSA contracted in the hospital ICU. The prevalence of the
      Chilean clone was 76.5% at entry and 88.9% for follow-up patients. Of the 113
      patients colonized with MRSA, nosocomial infection was present in 18 patients
      (16.0%). Three community-acquired MRSA isolates related to the USA300-0114
      pandemic clone were identified. These were also positive for Panton-Valentine
      leucidin cytotoxin genes of S.aureus. CONCLUSIONS: This is the first report in
      Colombia of patients colonized with CA-MRSA-ST8-SCCmec IVc isolates, and it is a
      probable source of dissemination of this bacteria in Colombian hospitals.

PMID- 21713338
TI  - [Drug-resistant Mycobacterium tuberculosis in children under 15 years].
AB  - INTRODUCTION: Tuberculosis is a widespread and increasingly important infectious
      disease. A third of the world-wide population is infected. Every year nine
      million cases occur in the world, one million of them appearing in children under
      15 years old. In Colombia alone, 719 cases were reported for the year 2008.
      OBJECTIVE: The incidence of Mycobacterium tuberculosis resistant forms was
      characterized in children under 15 years old in Colombia. MATERIALS AND METHODS:
      Mycobacterium tuberculosis drug susceptibility test data from 2001 to mid year
      2009 were analyzed at the Laboratorio Nacional de Referencia, Instituto Nacional
      de Salud, Bogota, Colombia. Cases were evaluated by patient age, disease
      geographic location, and type of sample, as well as the proportions of TB/HIV
      coinfections and drug resistance. RESULTS: Of the 128 patients examined, 66 were
      female (52%) and 62 were male (48%). The age group 0 to 5 years old consisted of
      59 cases (46%), 21 cases were 6 to 10 years old (16%) and 48 cases 11 to 14 years
      old (37.5%). The types of disease were 89 (69.6%) pulmonary, 34 (26.4%)
      extrapulmonary, and 5 (3.9%) cases without data. TB/VIH coinfection cases were
      7(5.4%). 123 (96%) untreated cases and 5 (2.34%) cases previously treated. Global
      resistance among the untreated cases was 21.1% and MDR-TB was 6.5%. CONCLUSION:
      This analysis demonstrated weaknesses in following established procedures in the
      TB treatment process, thereby impeding the diagnosis and the identification of
      drug resistance s in children under 15 years old. Approaches to improving
      treatment standards is a topic which requires further exploration.

PMID- 21713339
TI  - [Antimicrobial resistance of Gram negative bacilli isolated from tertiary-care
      hospitals in Colombia].
AB  - INTRODUCTION: Antimicrobial resistance has been identified as one of the major
      public health problems worldwide. To facilitate its control, bacterial resistance
      levels must be monitored permanently by effective surveillance systems.
      OBJECTIVE: To describe the antimicrobial resistance patterns of Gram negative
      bacilli in Colombian hospitals over a 3-year period. MATERIALS AND METHODS: This
      descriptive study used the bacterial susceptibility profiles provided by 14
      tertiary-care hospitals belonging to the Colombian Nosocomial Resistance Study
      Group. The hospitals were located in 7 major cities in Colombia, and provided
      records over the period January 2006 to December 2008. Using WHONET 5.4, the
      antimicrobial resistance patterns were described for the Enterobacteriaceae
      (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) and non
      fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii). Comparisons were
      made in the bacterial responses to selected antibiotics in samples from general
      wards and from adult intensive care units. RESULTS: The antimicrobial resistance
      frequencies of several Enterobacteriaceae species showed a decreasing trend. In
      contrast, P. aeruginosa was demonstrated to be a multidrug-resistance organism
      with increasing resistance frequencies. CONCLUSIONS: These data emphasize the
      importance of surveillance programs in detecting presence of multidrug-resistant
      organisms. This information will aid the implementation of protocols aimed to
      strengthen the infection control strategies and antibiotic stewardship in each
      hospital.

PMID- 21713340
TI  - [Distribution and ecoepidemiology of the triatomine fauna (Hemiptera: Reduviidae)
      in Margarita Island, Bolivar, Colombia].
AB  - INTRODUCTION: Information concerning to triatomine diversity and some eco
      epidemiologic aspects on Margarita Island has been recorded only from two of the
      five counties on the island. Knowledge about species habitat and their natural
      infection is essential to establish the risk for Chagas disease in endemic areas.
      OBJECTIVE: The distribution of triatomine insect fauna and its infection with
      Trypanosoma cruzi was described in order to establish and to stratify the risk of
      Chagas disease transmission. MATERIAL AND METHODS: Each of the 5 counties on
      Margarita Island were surveyed for triatomid insects inside and outside each
      dwelling. In the extradomicilary area, searches were conducted in the palms and
      bird nests located within forests and in pastures near domiciles. Infection with
      T. cruzi was determined amplifying by PCR the DNA extracted from triatomine
      feces. RESULTS: Five species of Reduviidae were recovered among the 1,154
      triatomines captured in the 5 counties. Triatoma maculata and Rhodnius pallescens
      showed high infection rates within dwellings and as well as in the peridomestic
      areas in Mompos and Talaigua Nuevo. On the palm trees, only R. pallescens and
      Eratyrus cuspidatus were found infected, and only in San Fernando and Margarita.
      In Cicuco, only R. pallescens was infected. Presence of Triatoma dimidiata was
      also ascertained. CONCLUSION: Infected triatomines were present in houses and on
      palm trees in all counties on the island. These observations indicate a potential
      risk of Chagas across the entire island; furthermore the presence of T.
      dimidiata, a very efficient Chagas vector, emphasizes the need to establish its
      epidemiological status on the island.

PMID- 21713341
TI  - [Detection of chromosome 17 aneuplody and TP53 gene deletion in a broad variety
      of solid tumors by dual-color fluorescence in situ hybridization (FISH)].
AB  - INTRODUCTION: TP53 is a tumor suppressor gene located on chromosome 17p13.1. This
      gene is essential for the control of cell cycle and has been found altered in
      about 50% of all tumor types. OBJECTIVE: The presence of aneuploidy of chromosome
      17 and TP53 gene deletion at 17p13.1 locus was determined in primary solid tumors
      using the dual-color FISH (fluorescence in situ hybridization). MATERIALS AND
      METHODS: Thirty-eight samples consisted of several types of primary solid tumors.
      All samples were mechanically and enzymatically disaggregated with 0.2%
      collagenase prior to obtaining interphase nuclei. The dual-color FISH was
      performed using direct fluorescent labeling probes for the chromosome 17
      centromere (green signal) and for the TP53 gene locus-specific (orange signal).
      RESULTS: Characteristic aneuploidy on chromosome 17 was found in 63% (24/38) of
      the samples. Monosomy occurred most frequently (75%, 18/24), followed by trisomy
      (17%, 4/24); nullisomy and tetrasomy were less frequent. TP53 gene deletion was
      found in 89.5% (34/38) of cases. Only four tumors were normal for copy number of
      chromosome 17 and TP53 gene. The histopathologic study showed that most of the
      samples were malignant tumors. CONCLUSIONS: Aneuploidy of chromosome 17 and
      deletion at 17p13.1 locus of TP53 gene were genetic alterations found to be very
      frequent in solid tumors. The dual-color FISH was able to detect both numerical
      and structural chromosomal abnormalities in interphase nuclei.

PMID- 21713342
TI  - The salivary glands of two sand fly vectors of Leishmania: Lutzomyia migonei
      (Franca) and Lutzomyia ovallesi (Ortiz)(Diptera: Psychodidae).
AB  - INTRODUCTION: Leishmaniasis is a vector-borne disease transmitted by the
      intradermal inoculation of Leishmania (Kinetoplastida: Trypanosomatidae)
      promastigotes together with saliva during the bite of an infected sand fly.
      OBJECTIVE: The salivary glands were compared from two vector species, Lutzomyia
      ovallesi (Ortiz,1952) and Lutzomyia migonei (Franca,1920) (Diptera: Psychodidae).
      MATERIAL AND METHODS: Protein profiles by SDS PAGE of salivary glands were
      compared among species as well as their development at several times post
      feeding. First, mice were immunized to salivary proteins by exposure to biting by
      L. ovallesi and of L. migonei. Antibodies in these mice against salivary gland
      specific proteins were evaluated by immunoblotting. RESULTS: No apparent change
      was revealed in the kinetic expression of salivary proteins induced by the
      different physiological states post feeding. Qualitative and quantitative
      variations were detected in16-18 polypeptides with molecular weights ranging from
      6 to 180 kDa. Species-specific proteins were demonstrated for L. migonei and L.
      ovallesi. In addition, antibodies against salivary gland specific proteins were
      found in mice immunized by the saliva of both species. CONCLUSION: Basic
      information was obtained concerning the nature of salivary gland proteins of L.
      migonei and L. ovallesi. This information helps to elucidate the role of salivary
      proteins and their potential as effective tools in screening risk factors in
      human and other vertebrate hosts.

PMID- 21713343
TI  - [Genetic and bioenvironmental factors associated with warfarin response in
      Colombian patients].
AB  - INTRODUCTION: Warfarin is an anticoagulant that is difficult to administer
      because of its narrow therapeutic margin and the numerous factors that influence
      patient response. OBJECTIVE: Demographic, clinical and genetic variables were
      characterized to establish the appropriate maintenance dosages of warfarin.
      MATERIALS AND METHODS: The Colombian patients consisted of 145 adults of both
      sexes. They were in stable anticoagulation status with international normalized
      ratio between 2 and 3 for at least two months, and without changes in the
      warfarin commercial preparation or in the dosage. After signing the informed
      consent, the following data was recorded for each volunteer: age, gender, weight,
      height, smoker status, co-morbidity, co-medication, International Normalized
      Ratio (INR), warfarin dose, and commercial brand. Each patient was typed for
      genes CYP2C9, VKORC1, CYP4F2 and PROC; for 59 patients, the serum levels of
      warfarin were quantified. The genotyping and the blood quantification were
      performed by mini-sequencing and HPLC methods, respectively. RESULTS: Age, co
      medication with enzymatic inhibitors (amiodarone, sertraline, fluoxetine) or
      inducers (phenytoin, carbamazepine), and the alleles rs1799853 (*2) and rs1057910
      (*3) of the CYP2C9 gene, as well as rs9923231 of the VKORC1 gene were associated
      with warfarin dose required to achieve anticoagulation with INR of 2-3. These
      variables were included in a multiple linear regression model for predicting the
      optimum dose/week of warfarin. This resulted in an algorithm that explained 47.4%
      of the variability in the dose responses. CONCLUSION: Clinical and
      pharmacogenetic variables provided a basis for improving the safety and effective
      dosage of warfarin; however, the use of a pharmacogenetic algorithm will require
      patient data obtained during clinical trials.

PMID- 21713344
TI  - [Microbiological and chemical quality of water used in Colombian food
      industries].
AB  - INTRODUCTION: Food safety is a public health concern that is recognized
      worldwide. Food-borne diseases affect millions of people throughout the world,
      although mainly in developing countries. The current study was performed within
      the framework of an inter-administrative agreement in Colombia that considers
      decisions for improving the sanitary status of products from the agrofood
      industry in Colombia. OBJECTIVE: Water used in Colombian food industries was
      assessed for its hygienic and sanitary qualities. MATERIALS AND METHODS: The
      descriptive cross sectional study included 66 industries located in eight
      geographic provinces across Colombia, including the Capital District of Bogota.
      The analytical determinations included 13 physical-chemical parameters, three
      bacteriological parameters, organophosphate and carbamate levels and presence of
      10 metals. Half of the industries were associated with production of dairy
      products and the other half with the meat-packing industry. RESULTS: Using the
      the current standards for human drinking water, the risk index of the food
      industry water samples was high for 4.5% of these industries, moderate risk for
      34.8%, low risk for 16.7% and for 43.9%, no risk. The parameters with the highest
      number of samples not in compliance with water health standards were
      microbiological (21.2%) and residual chlorine (28.8%). CONCLUSIONS: The results
      showed that the water used in most food industries can produce food spoilage and
      transmission of pathogen microorganisms. Importance is stressed for organizing a
      constant program of monitoring and control of water usage in food industries.

PMID- 21713345
TI  - [Clinical evidence of trachoma in Colombian Amerindians of the Vaupes Province].
AB  - INTRODUCTION: Trachoma is the leading cause of infectious blindness in the world.
      In 2008 there were 1,300,000 persons with blindness caused by trachoma and 8
      million with trichiasis, which might eventually lead to blindness. In Latin
      America it has been documented in Brazil, Guatemala and Mexico. OBJECTIVE: To
      inform the presence of trachoma for the first time in Colombia, amongst
      Amerindians of the Department of Vaupes. MATERIALS AND METHODS: In 2003 and 2006
      the Amerindian Maku communities of San Joaquin and Santa Catalina, located 5 km
      from the border with Brazil, were visited. From 2007 to 2009, San Gerardo, San
      Gabriel and Nuevo Pueblo, at a 35 km distance from San Joaquin were visited.
      RESULTS: In 2006 114 people were examined in Santa Catalina and San Joaquin; 21
      patients were clinically diagnosed with trachoma (18.4%), 15 (13.2%) of them
      children under 15 years old. All trachoma phases were observed. Three women had
      corneal opacity with poor vision. In the remaining three communities, three women
      with advanced trachoma with corneal opacity and blindness were detected. The poor
      quality of living conditions without fresh water and adequate sanitary disposal
      systems, and the abundance of flies identified as Hippelates sp., are risk
      factors for the transmission of the disease. DISCUSSION: Trachoma exists in
      Colombia, and it is frequent among the studied communities. Its focalized
      distribution makes it amenable to elimination. It is advisable to search for
      trachoma in other indigenous communities in Vaupes with similar living
      conditions.

PMID- 21713346
TI  - [New approaches for allergen-specific immunotherapy].
AB  - Rates of allergic diseases such as asthma and rhinitis are on the rise as
      important health problems in every country of the world. Allergen specific
      immunotherapy with natural allergenic extracts is a treatment directed to
      changing the natural course of these diseases, and is a treatment that has
      reported beneficial effects in a majority of allergic patients. However, this
      treatment is difficult because of the complex composition of the extracts. The
      composition is difficult to standardize and, consequently, the risk of
      anaphylactic shock is increased; furthermore, sensitization can occur to other
      antigens present in the extract. Therefore, new allergen specific immunotherapy
      approaches are needed. Chemically defined and standardized antigens are more
      easily managed and provide a safer and more efficient treatment. Vaccines for
      immunotherapy have already been designed, based on recombinant allergens,
      variants (or peptides derived from them), that can be administrated alone or in
      combination with adjutants. Some of these preparations are indicated for
      facilitating the uptake and antigenic presentation by dendritic cells, or by
      targeting the mast cells and basophiles. Studies in vitro, in animal models and
      clinical trials in allergic patients, indicate that these preparations may
      provide protection against the allergen exposure and improve the symptoms by
      inducing the production of blocking antibodies of the IgE mediated response,
      production of regulator T cells and cytokines of Th1 profile.

PMID- 21713347
TI  - [Malaria and social health determinants: a new heuristic framework from the
      perspective of Latin American social medicine?].

PMID- 21713348
TI  - [Biomedica, 30 years of devotion and compromise].

PMID- 21713349
TI  - [Kikuchi-Fujimoto disease: pediatric case presentation].
AB  - Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis is a rare,
      benign condition, usually self-limited to a six-month period. Classic clinical
      presentation is characterized by cervical lymphadenopathy, leukopenia and
      prolonged fever. It affects principally young, Asiatic adult women, although a
      few cases in the pediatric population have been reported. This disease frequently
      mimics tuberculous lymphadenitis, malign lymphoma, systemic lupus erythematosus
      and other benign and malignant conditions. The etiology is unknown, although a
      viral or autoimmune pathogenesis has been suggested. Laboratory investigations
      are usually unremarkable, and the most frequent findings are leukopenia, elevated
      erythrocyte sedimentation rate, anemia and positive antinuclear antibodies. To
      make an accurate diagnosis, histopathological studies are required. To avoid the
      use of antibiotics (which have no effect), early diagnosis is necessary. Herein
      the case of a 10 years old girl is described that presented with high, prolonged
      fever and marked cervical lymphadenopathy secondary to Kikuchi-Fujimoto disease.

PMID- 21713350
TI  - Pentalogy of Cantrell: report of a case with consanguineous parents.
AB  - Pentalogy of Cantrell is a syndrome evidencing five anomalies: a midline, upper
      abdominal wall abnormality; lower sternal defect; anterior diaphragmatic defect;
      diaphragmatic pericardial defect, and congenital abnormalities of the heart. Its
      prevalence is one in every 65,000 live births and a survival rate that is low if
      the fall the five defects are present or the gravity of the cardiac anomalies. It
      may be diagnosed during the first trimester obstetric ultrasound. For postnatal
      care, emission-computed tomography and magnetic resonance imaging is recommended
      for a clear definition of the extent of the defect and to design a course of
      corrective surgery. Herein, a case of pentology of Cantrell is reported for a
      child offspring of consanguineous parents.

PMID- 21713351
TI  - [Clinical, epidemiological and microbiological characteristics of a cohort of
      pulmonary tuberculosis patients in Cali, Colombia].
AB  - INTRODUCTION: The World Health Organization recommended strategy for global
      tuberculosis control is a short-course, clinically administered treatment, This
      approach has approximately 70% coverage in Colombia. OBJECTIVE: The clinical,
      epidemiological and microbiological characteristics along with drug therapy
      outcomes were described in newly diagnosed, pulmonary tuberculosis patients.
      MATERIALS AND METHODS: This was a descriptive study, conducted as part of a
      multicenter clinical trial of tuberculosis treatment. A cohort of 106 patients
      with pulmonary tuberculosis were recruited from several public health facilities
      in Cali between April 2005 and June 2006. Sputum smear microscopy, culture, drug
      susceptibility tests to first-line anti-tuberculosis drugs, chest X- ray and HIV
      ELISA were performed. Clinical and epidemiological information was collected for
      each participant. Treatment was administered by the local tuberculosis health
      facility. Food and transportation incentives were provided during a 30 month
      follow-up period. RESULTS: The majority of patients were young males with a
      diagnostic delay longer than 9 weeks and a high sputum smear grade (2+ or 3+).
      The initial drug resistance was 7.5% for single drug treatment and 1.9% for
      multidrug treatments. The incidence of adverse events associated with treatment
      was 8.5%. HIV co-infection was present in 5.7% of the cases. Eighty-six percent
      of the patients completed the treatment and were considered cured. The
      radiographic presentation varied within a broad range and differed from the
      classic progression to cavity formation. CONCLUSION: Delay in tuberculosis
      diagnosis was identified as a risk factor for treatment compliance failure. The
      study population had similar baseline epidemiologic characteristics to those
      described in other cohort studies.

PMID- 21713352
TI  - [Nodular hepatic lesions secondary to myeloma IgA presenting as fever of unknown
      origin].
AB  - A 45 year old male presented with IgA multiple myeloma s/p (status post)
      autologous hematopoietic stem cell transplantation; and with a history of six
      weeks of fever and constitutional symptoms. Liver tests showed an infiltrative
      pattern, with ultrasound evidence of multiple nodular lesions. A laparoscopic
      biopsy identified circumscribed myeloma foci. This is the first reported case of
      myeloma nodular liver lesions causing a fever of unknown origin.

PMID- 21713353
TI  - [Quality of life related to the health of the people affected by burns after the
      healing].
AB  - INTRODUCTION: Burn injuries affect the quality of life of the injured as a
      consequence of deformities and loss of bodily function. Objective. Changes in the
      quality of life related to the health were described in the people who had been
      affected by burns. MATERIALS AND METHODS: A cross-sectional descriptive study
      conducted in Medellin, Colombia, enrolled 130 people who suffered burns in the
      period 2001-2005. A standard quality-of-life survey consisting of 36 questions
      (the SF-36 scale) was administered. Statistical data were tested with Mann
      Whitney-U, Student-t, ANOVA, and Kruskal Wallis. Ethical considerations were met
      within the framework of resolution 8430/93 of the Colombian Ministry of National
      Health. RESULTS: The number of burns showed an increasing trend each year. Men
      were most often affected (66.9%) and severe burns were the most common (58%). The
      main burn sources were the fire flames, targeted attacks and gunpowder burns. The
      component of change of health upper obtained the average (55.3+/-19.2) and those
      of emotional performance (30.2+/-42.9), and physical performance (31.1+/-43.6)
      lowest, finding significant differences in those of physical performance
      (p=0.039) and general health (p=0.034) according to burn degree. CONCLUSION: In
      spite some inconsistency, the most affected quality-of-life components were the
      physical and emotional performance, with an overall presentation of a low quality
      of-life related to health.

PMID- 21713354
TI  - Correlation between malaria incidence and prevalence of soil-transmitted
      helminths in Colombia: an ecologic evaluation.
AB  - INTRODUCTION: Recent studies have suggested an association between the soil
      transmitted helminth infections and malaria incidence. However, published
      evidence is still insufficient and diverging. Since 1977, new ecologic studies
      have not been carried out to explore this association. Ecologic studies could
      explore this correlation on a population level, assessing its potential
      importance on public health. OBJECTIVES: The aim of this evaluation is to explore
      the association between soil-transmitted helminths prevalence and malaria
      incidence, at an ecologic level in Colombia. MATERIALS AND METHODS: Using data
      from the National Health Survey, which was carried out in 1980 in Colombia, we
      calculated Spearman correlation coefficients between the prevalence of: Ascaris
      lumbricoides, Trichuris trichiura and hookworm, with the 1980 malaria incidence
      data of the same year provided from the Colombian Malaria National Eradication
      Service. A robust regression analysis with least trimmed squares was performed.
      RESULTS: Falciparum malaria incidence and Ascaris lumbricoides prevalence had a
      low correlation (R2= 0.086) but this correlation was stronger into the clusters
      of towns with prevalence of Ascaris lumbricoides infection above 30% were only
      included (R2= 0.916). CONCLUSION: This work showed an ecologic correlation in
      Colombia between malaria incidence and soil-transmitted helminths prevalence.
      This could suggest that either there is an association between these two groups
      of parasites, or could be explained by the presence of common structural
      determinants for both diseases.

PMID- 21713355
TI  - [Teenage tobacco consumption in five Colombian cities].
AB  - INTRODUCTION: The consumption of tobacco is a public health problem around the
      world. In Colombia, each year approximately 17,000 deaths are attributed to
      smoking. The monitoring of tobacco consumption is necessary to estimate
      population risk for chronic diseases and cancer. OBJECTIVE: The prevalence of
      smoking was estimated and factors assessed that influence the use of tobacco
      among youths. MATERIALS AND METHODS: The survey was implemented by the Colombian
      National Cancer Institute in 2007, in public and private schools located in 5
      cities in Colombia. The survey was anonymous, voluntary and self-processed by
      students 13 to 15 years of age and the participants selected by a multi-stage
      sampling process. Statistical analysis was performed with SUDAAN software.
      Differences in proportions were considered statistically significant at the
      p<0.05 level. RESULTS: The average age of onset for tobacco consumption in the
      five cities was 11.9 years. The prevalence of cigarette smoking varied between
      7.4% and 34.1% among the cities and susceptibility to initiate smoking among non
      smokers was between 12.3% to 32.0%. Between 40% and 60% of students were exposed
      to secondhand smoke in public places. Approximately 70% were exposed to indirect
      tobacco advertising. Between 40% and 69% of students who currently smoke
      cigarettes reported that they wanted to stop smoking. Approximately 80% of
      students who currently smoke cigarettes were not refused when they purchased
      cigarettes in a store or supermarket. Finally, 34% to 54% of students reported
      having been taught in school about the harmful effects of smoking. CONCLUSIONS:
      The high prevalence of consumption in four of the five cities suggested
      interventions that aim primarily at prevention components, smoke-free spaces and
      advertising control.

PMID- 21713356
TI  - [Prevalence of respiratory symptomatic in health institutions of Bogota,
      Colombia].
AB  - INTRODUCTION: One of the greatest challenges in tuberculosis control is the early
      detection of cases. Detection is hindered by low level of active search for
      respiratory symptoms by health consultants and the small number of tubercular
      smear tests ordered by health personnel. OBJECTIVE: The prevalence of individuals
      with respiratory symptoms was estimated in Bogota Health Service Institutions,
      along with the proportion of those receiving diagnostic baciloscopies (smear or
      culture tests). MATERIALS AND METHODS: A cross sectional survey was carried out
      in 113 health service institutions located in the city of Bogota, involved 3,170
      users and covered a 10-month period between June 2005 and March 2006. Sampling
      design was based on a probabilistic, stratified, multistage, cluster-without
      replacement strategy. A telephone follow-up and review of laboratory registers
      was done to identify symptomatic individuals for whom baciloscopy was requested.
      RESULTS: The prevalence of symptomatic individuals was 7.5% (95%CI 6.4-8.6%). A
      higher prevalence occurred in public institutions, 9.5% (95%CI 8.0-10.9%), in
      institutions of first level, 8.6% (95%CI 7.4-9.8), in persons >= 60 years of age
      15.8% (95%CI 12.4-19.2%) and in health users with social security, 7.6% (95% CI
      6.4-8.7%). In 47% of symptomatic cases, a baciloscopic procedures were not
      ordered. CONCLUSIONS: The study updated the prevalence ofrespiratory symptomatic
      individuals in Colombia and due to the large sample size (and small confidence
      interval), inferences can be generalized to the entire health service system in
      Bogota. The current tuberculosis program goals in Bogota require adjustment based
      on the current prevalence of 7.5% compared with a 1977 estimate of 10%.. The
      study recommends an awareness program for physicians to use TB diagnostic tests
      in suspect cases.

PMID- 21713357
TI  - [Efficacy of the social mobilization and the social participation in dengue
      control measures].
AB  - INTRODUCTION: Dengue is a public health problem. However, the efficacy of typical
      control programs is not well-established. OBJECTIVE: The efficacy of social
      mobilization was assessed for its role in public empowerment in the improvement
      of dengue control measures. MATERIALS AND METHODS: A community trial was
      conducted in Comuna Norte, a section of the city of Bucaramanga,Santander. Four
      high-incidence neighborhoods were selected--two received empowerment training and
      two served as controls. During 1,968 home visits, information was collected
      concerning knowledge and practices of dengue control, and information was
      provided concerning dengue and mosquito larval habitats of the vector. At local
      schools, dengue control information was provided for 2,455 students. The
      intervention included training of 155 community leaders and tracking of
      prevention and control activities. Findings were compared between post
      intervention and controls by chi2 test, with a significance level of p<0.05.
      RESULTS: At the home visits, 80.7% of respondents were female. with a mean age of
      39.1 and 5.8 years schooling. In comparing the intervention neighborhoods with
      the controls, differences in knowledge about dengue were as follows: symptoms of
      bodily pain (chi2=21.0, p<0.001) and abdominal pain (chi2=5.1, p=0.024),
      reproduction cycle of the mosquito vector (chi2=11.5, p<0.001), knowledge of
      mosquitos characteristics (chi2=7.1, p=0.008). In washing practices batteries
      (chi2=7.2, p=0.007), spraying (chi2=7.0, p<0.008), use of bednets (chi2=49.8,
      p<0.001), consulting a physician (chi2=8.2, p=0.004), participate in meetings
      (chi2=29.6, p<0.001), prevention methods (chi2=10.4, p=0.013), willingness to
      lead anti-mosquito campaigns (chi2=6.8, p= 0.009) and to get help for programs
      (chi2=5.8, p=0.016). There was a decrease in the proportion of households with
      larvae from 20.0% to 15.9% in both groups. The difference in prevalence of dengue
      one year after initiation of the program was not significant--4.8% in the
      intervention group and 6.7% in control (chi2=3.4, p=0.065). CONCLUSION: The
      social mobilization was effective for improving actions of empowerment, control,
      but not dengue prevention.

PMID- 21713358
TI  - [Genotypic survey of Plasmodium falciparum based on the msp1, msp2 and glurp
      genes by multiplex PCR].
AB  - INTRODUCTION: The genetic diversity of Plasmodium falciparum has been one of the
      major obstacles for the success of anti-malaria drug therapy. It provides the
      parasite an ability to evade the host's immune response by generating changes in
      its antigenic composition and resistance to antimalarial drugs. OBJECTIVE: The
      genetic diversity of P.falciparum was characterized in 4 Colombian localities
      through the analysis of polymorphic genes. MATERIALS AND METHODS: Eighty-one
      samples were obtained from patients with uncomplicated P. falciparum malaria and
      screened for polymorphic variants of msp1, msp2 (merozoite surface proteins) and
      glurp (glutamate-rich protein) with a multiplex PCR assay. The geographic regions
      sampled were Tierralta (Cordoba), in northwestern Colombia and in the Orinoco
      river watershed of eastern Colombia--Inirida (Guainia), La Carpa (Guaviare), and
      Casuarito (Vichada). RESULTS: The MAD20 variant was detected in all samples
      analyzed for the msp1 gene. For the msp2 gene, the IC allelic family was found in
      96.3% of the samples as compared to 4.9% of the samples with the FC family. Both
      families showed size polymorphism with bands between 467 and 513 basepairs (bp)
      for IC and 286 and 300 bp for FC. PCR products of differing sizes were detected
      for the glurp gene and grouped into 5 size classes: I (600-699 bp) 2.5%, II (700
      799 bp) 19.8%, III (800-899 bp) 72.8%, IV (900-999 bp) 1.2% and V (1000-1099 bp)
      3.7%. CONCLUSIONS: The msp1 molecular marker did not provide information for
      differentiating P. falciparum parasite populations. The msp2 gene was more
      suitable for studying the genetic diversity, however, further studies are
      required to identify polymorphisms within the two allelic families. The glurp
      gene showed a great genetic diversity of circulating P. falciparum populations,
      and suggested that this gene may be useful for distinguishing between
      recrudescence and reinfection.

PMID- 21713359
TI  - [Insulin-like growth factor receptor I signaling in a breast cancer cell line].
AB  - INTRODUCTION: In vitro studies strongly suggest that proliferation, migration and
      cell survival of breast cancer cell lines are significantly affected by
      activation of the IGF type 1 receptor (IGF-IR). OBJECTIVE: The phosphorylation by
      IGF-I of IGF-IR and the intracellular signaling molecules Akt (PI-3K pathway) and
      Erk1/2 (MAPK pathway) was characterized in a human breast cancer cell lines.
      MATERIALS AND METHODS: The study compared a standard breast adenocarcinoma line
      (MCF-7) cell line with a line (CSC 1595) derived from an infiltrating ductal
      breast cancer in a Colombian patient. The CSC 1595 and MCF-7 cell lines were
      cultured in DMEM supplemented with 10% fetal bovine serum, 2 mM glutamine, 100
      U/ml penicillin, and 100 ug/ml streptomycin and grown at 37  degrees C in 5% CO2
      atmosphere and 95% humidity. Cell extracts were prepared, followed by
      immunoprecipitation and immunoblotting with specific anti-pIGF-IR, anti-pERK1/2
      and anti-pAkt antibodies. RESULTS: After 5 minute stimulation with IGF-I, 70% of
      the IGF-IR was phosphorylated in the cell line CSC 1595 and 25% in MCF-7. In
      addition, Akt (oncogene protein v-akt) and ERK1/2 (extracellular signal-regulated
      MAP kinases) were phosphorylated. Basal and stimulated levels of phosphorylated
      ERK1/2 were substantially higher compared to those in the MCF-7 cell line.
      CONCLUSIONS: The IGF-IR and MAPK kinase pathway involving proteins ERK1/2 showed
      more significant phosphorylation in the 1,595 cells compared to the observed in
      the MCF-7 cell line. Since the IGF-IR is the major activator of this pathway it
      may play an important role in ductal infiltrating breast cancer tumor growth and
      metastases.

PMID- 21713360
TI  - [Risk factors for premature coronary disease in women].
AB  - INTRODUCTION: Coronary disease is the leading cause of death in women, and
      consequently, identification of cardiovascular risk factors must be a priority.
      Recent studies have linked pregnancy disturbances and coronary disease, but this
      hypothesis has remained unproved in Hispanic women. OBJECTIVE: The association of
      traditional risk factors and pregnancy disturbances with coronary heart disease
      was assessed in a sample of women with premature coronary disease. MATERIALS AND
      METHODS: The case control study included only women <55 years old, who had
      undergone a coronary angiography. Two hundred women were included, 100 without
      and 100 with coronary disease, and with mean ages of 46.5+/-4.3 and 49.5+/-3.7
      years, respectively. Logistic regression analysis was used to assess the
      relationship between risk factors and coronary disease. Crude and multivariate
      adjusted odds ratios with 95% confidence intervals were calculated. RESULTS:
      Univariate analysis showed an association between coronary disease and the past
      medical history of preeclampsia, premature delivery, low birth weight, diabetes,
      hypercholesterolemia and smoking habit. Logistic regression analysis showed an
      association of premature delivery (OR=6.0, 95%CI 2.3-15.0, p<0.01),
      hypercholesterolemia (OR=4.1, 95%CI 2.1-7.8, p<0.01) and smoking habit (OR=1.7,
      95%Ci 0.9-3.2, p=0.08). The practice of regular physical activity was identified
      as a protection factor (OR=0.5, 95%CI 0.3-1.0, p=0.04). CONCLUSION: Pregnancy
      disturbances and traditional risk factors were related to an increased risk of
      coronary artery disease in a Hispanic population of women with premature coronary
      disease.

PMID- 21713361
TI  - [Endovascular coil occlusion of 473 intracranial aneurysms: angiographic and
      clinical results].
AB  - INTRODUCTION: Endovascular therapy is a technique accepted throughout the world
      for the treatment of ruptured and non-ruptured intracranial aneurysms. In
      Colombia, however, no summary data have been published that validate the method
      in terms of occlusion grade and morbimortality. OBJECTIVE: The clinical and
      angiographic outcomes were evaluated for endovascular embolization of 473
      intracranial aneurysms treated during a 12 year time interval. MATERIALS AND
      METHODS: Between 1996-2008, 473 intracranial aneurysms treated by an endovascular
      approach were included in the current retrospective study. Pre and postprocedural
      angiographic images were analyzed, and clinical outcome was recorded according to
      the Glasgow coma scale. Immediate angiographic results and morbimortality were
      evaluated. RESULTS: The technical feasibility of the procedure was 96.8%.
      According to Hunt and Hess scale, 8.7% patients were classified as grade I, 35.7%
      grade II, 19.2% grade III and 7.8% grades IV/V. Non-ruptured aneurysms had
      occurred in 28.5% of patients. Immediate procedural angiography demonstrated
      total occlusion in 69.6%, neck remnant in 17.5% and partial or failed occlusion
      in 16.1%. Global mortality was 10.4% and procedural mortality was 1.5%. Technique
      associated complications presented in 7.6% of treated aneurysms. CONCLUSION:
      Endovascular treatment of intracranial aneurysms was associated with low
      morbimortality and high technical feasibility. The results are comparable with
      other published data summaries and supporting the use of the method in Colombia.

PMID- 21713362
TI  - Implication of NF-kappaB and p53 in the expression of TRAIL-death receptors and
      apoptosis by apple procyanidins in human metastatic SW620 cells.
AB  - INTRODUCTION: The nuclear factor-kappaB (NF-NF-kappa) has been shown to
      upregulate pro-apoptotic mediators such as TRAIL-DR4/-DR5 receptors and the p53
      transcription factor depending on the type of stimulus and the cell type
      involved. Previously, apple procyanidins (Pcy) have been shown to upregulate the
      expression of TRAIL-DR4/-DR5 and thereby overcoming the resistance of human colon
      cancer-derived metastatic SW620 cells to TRAIL. OBJECTIVES: NF-kappaB and p53
      were investigated for their involvement in the Pcy-triggered apoptosis of human
      derived-metastatic colon cancer (SW620) cells. MATERIALS AND METHODS: Cell death,
      p53, TRAIL-DR4/-DR5 proteins were analyzed by flow cytometry. DR4/DR5 mRNA was
      analyzed by RT-PCR in real time. Activated p50/p65 and p53 forms were studied by
      ELISA and immunoblotting RESULTS: Pcy-triggered cell death was prevented by
      specific inhibitors of NF-kappaB and of p53: amino-4-(4-phenoxy-phenylethylamino)
      quinazoline (QNZ) and pifithrin alpha (Palpha), respectively. QNZ and Palpha
      inhibited the Pcy-dependent activation of TRAIL-DR4/-DR5 death receptors.
      However, the upregulation of TRAIL-DR4 by Pcy was significantly decreased only
      when NF-kappaB and p53 inhibitors were used in combination; this effect was not
      observed with a single inhibitor. This effect was not observed for TRAIL-DR5 and
      suggested that the expression of each TRAIL-death receptor may be regulated
      differently. CONCLUSIONS: These data suggested that NF-kappaB and p53 are
      partially required in Pcy-triggered apoptosis of SW620 cells by up-regulating the
      expression of TRAIL-DR4/-DR5. In addition, the ratio between TRAIL-DR4/-DR5 may
      be a determining factor in the activation of TRAIL-death receptor mediated
      apoptosis.

PMID- 21713363
TI  - [Comparison of the transcriptional profiles of patients with dengue fever and
      dengue hemorrhagic fever reveals differences in the immune response and clues in
      immunopathogenesis].
AB  - INTRODUCTION: Dengue infection demonstrates a wide spectrum of clinical
      manifestations from mild disease (dengue fever) to severe dengue hemorrhagic
      fever, but the immunopathogenic mechanisms involved in disease severity are not
      clear. OBJECTIVE: Differentially expressed genes associated to immune response
      were identified from peripheral blood mononuclear cells of Colombian children
      with dengue fever and dengue hemorrhagic fever. MATERIALS AND METHODS: Microarray
      analysis was used as a tool to establish and compare transcriptional profiles of
      peripheral blood mononuclear cells of six children in acute phase of dengue fever
      and dengue hemorrhagic fever. The commercial gene chip used was Affymnetrix
      GeneChip HG_U133_Plus_2. RESULTS: Dengue hemorrhagic fever patients expressed
      interleukin 6, chemokines, complement proteins and pentraxin 3, along with the
      lymphocyte inhibitors lymphocyte-activation gene 3 and cathepsin L1. An
      interaction model for these genes showed tissue factor playing a central role in
      the network generated. In contrast, dengue fever patients expressed cytokines,
      complement and the leukotrienes inhibitors lactotransferrin, C1 inhibitor, and
      leukotriene-B (4-omega-hydroxylase 2). CONCLUSIONS: These results indicate that
      in dengue fever, cytokine and complement inhibitors are able to limit endothelial
      damage and prevent increases in vascular permeability, whereas dengue-
      hemorrhagic fever patients have immune cell dysfunction and unregulated
      complement and cytokine action. This leads to "hypercoagulation" and endothelial
      damage, thereby increasing disease severity. Verification of the pathogenic role
      of the identified molecules will contribute to understanding of dengue
      pathogenesis and lead to rational development of therapeutic drugs.

PMID- 21713364
TI  - Intratumoral lymphocyte density in serous ovarian carcinoma is superior to ERCC1
      expression for predicting response to platinum-based therapy.
AB  - Intratumoral immune cells and ERCC1 expression are likely to play a role in the
      response of ovarian carcinoma to chemotherapy, but their impact on therapy
      outcome is still unclear. Therefore, 41 cases of optimally resected high grade
      serous ovarian carcinomas were examined retrospectively for stromal and
      intraepithelial lymphocyte populations and ERCC1 status in relation to response
      to platinum-based therapy. Based on RECIST criteria, 27 patients were classified
      as responsive and 14 as therapy resistant, respectively. Using
      immunohistochemistry for CD3, CD8, CD4, TIA1, MUM1 and FOX P3 on representative
      tumor sections, we quantitatively evaluated the intratumoral density of
      lymphocyte subpopulations. In addition, ERCC1 protein and mRNA expression were
      determined by immunohistochemistry using the Steffensen score and quantitative RT
      PCR, respectively. Furthermore, ERCC1 SNP's C8092A and codon 118 were analysed.
      Response to chemotherapy was significantly associated with higher numbers of
      stromal CD3+ (mean 21.33 lymphocytes/HPF versus 8.21 lymphocytes/HPF, p = 0.002)
      and CD8+ lymphocytes (mean 9.22 lymphocytes/HPF versus 4.57 lymphocytes/HPF, p =
      0.013). Counts of intraepithelial CD3+ and CD8+ lymphocytes, stromal and
      intraepithelial FOXP3+ and TIA1+ cells, CD4+ lymphocytes, and MUM1+ plasma cells
      did not reach statistical significance. Neither ERCC1 protein expression (p =
      0.232) nor SNPs codon 118 and C8092A of the ERCC1 gene (p = 0.269 and p = 0.543)
      showed an association with therapy response. The same was true for ERCC1 mRNA
      levels (p = 0.896), probably due to intratumoral lymphocyte contamination. In
      conclusion, the density of CD3+ and CD8+ T-cells in tumor stroma proved to be a
      significant predictor for response to platinum-based therapy, whereas examination
      of ERCC1 failed to identify therapy-responsive patients.

PMID- 21713365
TI  - Genetic markers of oral malignant melanoma analysed by fluorescence in situ
      hybridisation (FISH).
AB  - Oral malignant melanoma (OMM) is a rare condition, and our knowledge about
      morphological and genetic modifications is scanty and incomplete. The aim of this
      study is to report morphological and fluorescent in situ hybridisation (FISH)
      data obtained in four cases of OMM. FISH results were also compared with those of
      cutaneous malignant melanoma (CMM, three cases), desmoplastic cutaneous melanoma
      (DMM, four cases) and spindle cells cutaneous melanoma (SCCM, one case). All the
      OMM cases showed a combined radial and vertical growth pattern, with the invasive
      component characterised by malignant spindle cells intermingled among collagen
      bundles. Two cases of OMM resulted positively stained with p16, in contrast with
      frequent loss of immunoreactivity in CMM. Three OMM were suitable for FISH
      analysis: 9p21 locus was deleted in 1/3, 1p36 resulted deleted 3/3, while EGFR
      gene showed a relative deletion. Similar genetic alterations were found in DMM
      and SCMM, but not in CMM. Ultrastructural findings further enhanced differences
      between OMM and CMM; OMM displayed, mature-staged melanosomes only within in situ
      component. In conclusion, OMM presents a morphological and genetic profile
      similar to DMM; and SCCM, however, displays some differences from CMM.

PMID- 21713366
TI  - Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an
      independent predictor of survival in HCC.
AB  - Histone deacetylases (HDAC) are responsible for the transcriptional control of
      genes through chromatin remodeling and control tumor suppressor genes. In several
      tumors, their expression has been linked to clinicopathological factors and
      patient survival. This study investigates HDACs 1, 2, 3, and 7 expressions in
      hepatocellular carcinoma (HCC) and their correlation with clinical data and
      patient survival. Tissue microarrays of 170 surgically resected primary HCCs and
      adjacent uninvolved tissue were evaluated immunohistochemically for the
      expression of HDACs 1, 2, 3, 7, and Ki-67 and were analyzed with respect to
      clinicopathological data and patient survival. HDACs 1, 2, 3, and Ki-67 were
      expressed significantly higher in cancer cells compared to normal tissue (HDAC1:
      p = 0.034, HDACs 2 and 3 and Ki-67: p < 0.001), while HDAC7 expression did not
      differ between HCC and non-cancerous liver tissue. In tumor tissue HDACs 1-3
      expression levels showed high concordance with each other, Ki-67 and tumor grade
      (p < 0.001). High HDAC2 expression was associated with poor survival in low-grade
      and early-stage tumors (p < 0.05). The expression of the HDACs 1, 2, and 3 (but
      not HDAC7) isoenzymes correlates with clinicopathological factors, and HDAC2
      expression has an impact on patient survival.

PMID- 21713367
TI  - Estimating 3D lumen centerlines of carotid arteries in free-hand acquisition
      ultrasound.
AB  - PURPOSE: The purpose of this paper is to present a methodology to estimate the
      carotid artery lumen centerlines in ultrasound (US) images obtained in a free
      hand examination. Challenging aspects here are speckle noise in US images,
      artifacts, and the lack of contrast in the direction orthogonal to the US beam
      direction. METHOD: An algorithm based on a rough lumen segmentation obtained by
      robust ellipse fitting was developed to deal with these conditions and estimate
      the lumen center in 2D B-mode scans. In a free-hand sweep examination, continuous
      image acquisitions are performed through time when the radiologist moves the
      probe on the patient's neck. The result is a series of images that show 2D cross
      sections of the carotid's morphology. A tracking sensor (Flock of Birds) was
      attached to the probe and both were connected to a PC executing the Stradwin
      software, which relates spatial information to the acquisition data of the US
      probe. The spatial information was combined with the 2D lumen center estimates to
      provide a centerline in 3D. For validation, 19 carotid scans from 15 different
      patients were scanned, their centerlines calculated by the algorithm and compared
      with results acquired by manual annotations. RESULTS: The average Euclidean
      distance between both among all the examinations was 0.82  mm. For each
      examination, the percentage of these Euclidean distances below 2  mm was
      calculated; the average over all examinations was 92%. CONCLUSION: Automated 3D
      estimation of carotid artery lumen centerlines in free-hand real-time ultrasound
      is feasible and can be performed with high accuracy. The algorithm is robust
      enough to keep the centerlines inside the vessel, even in the absence of contrast
      in parts of the vessel wall.

PMID- 21713368
TI  - Phylogeny of members of the Frankia genus based on gyrB, nifH and glnII
      sequences.
AB  - To construct an evolutionary hypothesis for the genus Frankia, gyrB (encoding
      gyrase B), nifH (encoding nitrogenase reductase) and glnII (encoding glutamine
      synthetase II) gene sequences were considered for 38 strains. The overall
      clustering pattern among Frankia strains based on the three analyzed sequences
      varied among themselves and with the previously established 16S rRNA gene
      phylogeny and they did not reliably reflect clear evolution of the four discerned
      Frankia clusters (1, 2, 3 and 4). Based on concatenated gyrB, nifH and glnII,
      robust phylogenetic trees were observed with the three treeing methods (Maximum
      Likelihood, Parsimony and Neighbor-Joining) and  supported by strong bootstrap
      and posterior probability values (>75%) for overall branching. Cluster 4 (non
      infective and/or non-nitrogen-fixing Frankia) was positioned at a deeper branch
      followed by cluster 3 (Rhamnaceae and Elaeagnaceae infective Frankia), while
      cluster 2 represents uncultured Frankia microsymbionts of the Coriariaceae,
      Datiscaceae, Rosaceae and of Ceanothus sp. (Rhamnaceae); Cluster 1 (Betulaceae,
      Myricaceae and Casuarinaceae infective Frankia) appears to have diverged more
      recently. The present study demonstrates the utility of phylogenetic analyses
      based upon concatenated gyrB, nifH and glnII sequences to help resolve previously
      unresolved or poorly resolved nodes and will aid in describing species among the
      genus Frankia.

PMID- 21713369
TI  - Visual working memory contaminates perception.
AB  - Indirect evidence suggests that the contents of visual working memory may be
      maintained within sensory areas early in the visual hierarchy. We tested this
      possibility using a well-studied motion repulsion phenomenon in which perception
      of one direction of motion is distorted when another direction of motion is
      viewed simultaneously. We found that observers misperceived the actual direction
      of motion of a single motion stimulus if, while viewing that stimulus, they were
      holding a different motion direction in visual working memory. Control
      experiments showed that none of a variety of alternative explanations could
      account for this repulsion effect induced by working memory. Our findings provide
      compelling evidence that visual working memory representations directly interact
      with the same neural mechanisms as those involved in processing basic sensory
      events.

PMID- 21713370
TI  - A formal ideal-based account of typicality.
AB  - Inspired by Barsalou's (Journal of Experimental Psychology: Learning, Memory, and
      Cognition, 11, 629-654, 1985) proposal that categories can be represented by
      ideals, we develop and test a computational model, the ideal dimension model
      (IDM). The IDM is tested in its account of the typicality gradient for 11
      superordinate natural language concepts and, using Bayesian model evaluation,
      contrasted with a standard exemplar model and a central prototype model. The IDM
      is found to capture typicality better than do the exemplar model and the central
      tendency prototype model, in terms of both goodness of fit and generalizability.
      The present findings challenge the dominant view that exemplar representations
      are most successful and present compelling evidence that superordinate natural
      language categories can be represented using an abstract summary, in the form of
      ideal representations. Supplemental appendices for this article can be downloaded
      from http://mc.psychonomic-journals.org/content/supplemental.

PMID- 21713371
TI  - Early morphological decomposition during visual word recognition: evidence from
      masked transposed-letter priming.
AB  - The present experiments were designed to explore the theory of early morpho
      orthographic segmentation (Rastle, Davis, & New, Psychonomic Bulletin & Review
      11,1090-1098, 2004), which postulates that written words with a true
      morphologically complex structure (cleaner) and those with a morphological
      pseudostructure (corner) are both decomposed into affix and stem morphemes. We
      used masked complex transposed-letter (TL) nonword primes in a lexical decision
      task. Experiment 1 replicated the well-known masked TL-priming effect using
      monomorphemic nonword primes (e.g., wran-WARN). Experiment 2 used the same
      nonword TL stems as in Experiment 1, but combined them with real suffixes (e.g.,
      ish as in wranish-WARN). Priming was compared with that from nonsuffixed primes
      in which the real suffixes were replaced with nonmorphemic endings (e.g., el as
      in wranel-WARN). Significant priming was found in the suffixed but not in the
      nonsuffixed condition, suggesting that affix-stripping occurs at prelexical
      stages in visual word recognition and operates over early letter-position
      encoding mechanisms.

PMID- 21713372
TI  - Surgery of the primary tumor does not improve survival in stage IV breast cancer.
AB  - We sought to evaluate the survival of patients who received breast surgery prior
      to any other breast cancer therapy following a metastatic diagnosis. Standard
      treatment for stage IV breast cancer is systemic therapy without resection of the
      primary tumor. Registry-based studies suggest that resection of the primary tumor
      may improve survival in stage IV cancer. We performed a retrospective analysis
      using data from the National Comprehensive Cancer Network (NCCN) Breast Cancer
      Outcomes Database. Patients were eligible if they had a metastatic breast cancer
      diagnosis at presentation with disease at a distant site and either received
      surgery prior to any systemic therapy or received systemic therapy only. Eligible
      patients who did not receive surgery were matched to those who received surgery
      based on age at diagnosis, ER, HER2, and number of metastatic sites. To determine
      whether estimates from the matched analysis were consistent with estimates that
      could be obtained without matching univariate and multivariable analyses of the
      unmatched sample were also conducted. There were 1,048 patients in the NCCN
      database diagnosed with stage IV breast cancer from 1997 to 2007. 609 metastatic
      breast cancer patients were identified as eligible for the study. Among the 551
      patients who had data available for matching, 236 patients who did not receive
      surgery were matched to 54 patients who received surgery. Survival was similar
      between the groups with a median of 3.4 years in the nonsurgery group and 3.5
      years in the surgery group. The groups were similar after adjusting for the
      presence of lung metastases and use of trastuzumab therapy (HR=0.94, CI 0.83
      1.08, P=0.38). When matching for the variables associated with a survival benefit
      in previous studies, surgery was not shown to improve survival in the stage IV
      setting for this subset.

PMID- 21713374
TI  - Membranous nephropathy in an HIV-positive patient complicated with hepatitis B
      virus infection.
AB  - In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy
      should be considered when HIV infection is associated with heavy proteinuria. On
      the other hand, hepatitis B virus (HBV) may also play a role in the development
      of glomerular injury among patients with HIV infection, since HIV and HBV
      infections commonly occur together due to shared modes of transmission. We
      present here a case of nephrotic syndrome in an HIV-positive patient complicated
      with HBV infection. A renal biopsy revealed sparse granular deposits of
      immunoglobulin G in the subepithelial region, consistent with membranous
      nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis
      B core activity within glomeruli. These results led us to consider that HBV
      associated MN might play a role in the development of nephrotic syndrome.
      Although anti-viral treatment for patients with HBV-associated MN has been
      suggested to be clinically effective, the use of two anti-HIV agents (tenofovir
      and emtricitabine), both of which have anti-HBV activities, was not effective for
      the patient's nephrotic syndrome, despite obtaining a decrease in the serum HBV
      DNA levels. A lack of prospective data suggests that many decisions on the
      treatment of glomerulopathies with HIV infections are potentially empirical.
      Obviously, further studies and accumulated clinical experience are required to
      better determine the pathogenesis and management of HBV-associated MN among
      patients with HIV infections.

PMID- 21713375
TI  - Mitochondrial ATP-sensitive potassium channels enhance angiotensin-induced
      oxidative damage and dopaminergic neuron degeneration. Relevance for aging
      associated susceptibility to Parkinson's disease.
AB  - Recent studies have shown that renin-angiotensin system overactivation is
      involved in the aging process in several tissues as well as in longevity and
      aging-related degenerative diseases by increasing oxidative damage and
      inflammation. We have recently shown that angiotensin II enhances dopaminergic
      degeneration by increasing levels of reactive oxygen species and
      neuroinflammation, and that there is an aging-related increase in angiotensin II
      activity in the substantia nigra in rats, which may constitute a major factor in
      the increased risk of Parkinson's disease with aging. The mechanisms involved in
      the above mentioned effects and particularly a potential angiotensin-mitochondria
      interaction have not been clarified. The present study revealed that activation
      of mitochondrial ATP-sensitive potassium channels [mitoK(ATP)] may play a major
      role in the angiotensin II-induced effects on aging and neurodegeneration.
      Inhibition of mitoK(ATP) channels with 5-hydroxydecanoic acid inhibited the
      increase in dopaminergic cell death induced by angiotensin II, as well as the
      increase in superoxide/superoxide-derived reactive oxygen species levels and the
      angiotensin II-induced decrease in the mitochondrial inner membrane potential in
      cultured dopaminergic neurons. The present study provides data for considering
      brain renin-angiotensin system and mitoK(ATP) channels as potential targets for
      protective therapy in aging-associated diseases such as Parkinson's disease.

PMID- 21713376
TI  - Skeletal muscle contractile function and neuromuscular performance in Zmpste24 -/
      mice, a murine model of human progeria.
AB  - Human progeroid syndromes and premature aging mouse models present as segmental,
      accelerated aging because some tissues and not others are affected. Skeletal
      muscle is detrimentally changed by normal aging but whether it is an affected
      tissue in progeria has not been resolved. We hypothesized that mice which mimic
      Hutchinson-Gilford progeria syndrome would exhibit age-related alterations of
      skeletal muscle. Zmpste24 (-/-) and Zmpste24 (+/+) littermates were assessed for
      skeletal muscle functions, histo-morphological characteristics, and ankle joint
      mechanics. Twenty-four-hour active time, ambulation, grip strength, and whole
      body tension were evaluated as markers of neuromuscular performance, each of
      which was at least 33% lower in Zmpste24 (-/-) mice compared with littermates (p
      < 0.06). Contractile capacity of the posterior leg muscles were not affected in
      Zmpste24 (-/-) mice, but muscles of the anterior leg were 30-90% weaker than
      those of Zmpste24 (+/+) mice (p < 0.01). Leg muscles were 32-47% smaller in the
      Zmpste24 (-/-) mice and contained ~60% greater collagen relative to littermates
      (p < 0.01). Soleus and extensor digitorum longus muscles of Zmpste24 (-/-) mice
      had excessive myonuclei and altered fiber size distributions but, otherwise,
      appeared normal. Ankle range of motion was 70% lower and plantar- and
      dorsiflexion passive torques were nearly 3-fold greater in Zmpste24 (-/-) than
      Zmpste24 (+/+) mice (p <= 0.01). The combined factors of muscle atrophy, collagen
      accumulation, and perturbed joint mechanics likely contributed to poor
      neuromuscular performance and selective muscle weakness displayed by Zmpste24 (-/
      )mice. In summary, these characteristics are similar to those of aged mice
      indicating accelerated aging of skeletal muscle in progeria.

PMID- 21713377
TI  - Coronary flow reserve varies depending upon the location within the artery it is
      assessed and the TIMI myocardial perfusion grade: a PROTECT TIMI-30 analysis.
AB  - Coronary flow reserve (CFR) is a measure of the capacity of the epicardial
      coronary artery and the microvasculature to achieve maximal blood flow in
      response to hyperemic stimulation. It is not known whether the CFR varies along
      the length of the artery. Likewise, the interaction between CFR and the
      thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG) is
      unknown. CFR was measured using the number of cineframes required for the
      contrast to traverse the same length of the coronary artery before and following
      the administration of intracoronary adenosine. Following percutaneous coronary
      intervention (PCI), CFR was assessed both proximal and distal to the lesion in
      192 consecutive patients with non-ST-segment elevation acute coronary syndrome
      (NSTEACS) from the PROTECT TIMI-30 trial. TMPG was also assessed. The difference
      between the distal and proximal CFR for patients with TMPG 0/1 (n = 76) was 0.11
      (95% CI 0.01-0.20, P = 0.026), while among those with TMPG 2/3 (n = 114) it was 
      0.02 (95% CI -0.09-0.06, P = 0.65). The difference in the CFR between the distal
      and proximal segments among patients with TMPG 0/1 and TMPG 2/3 was significant
      (P interaction = 0.044). Following PCI among patients with impaired TMPG (0/1) in
      the setting of NSTEACS, CFR varies significantly between the proximal and distal
      segment of coronary arteries and is associated with higher (greater) distal CFR.

PMID- 21713378
TI  - Pharmacogenetic distribution of warfarin and its clinical significance in Korean
      patients during initial anticoagulation therapy.
AB  - During warfarin treatment, determining the optimal dose and maintaining the
      target PT-INR are challenging. Increasing evidence supports the theory that
      genotypic polymorphisms influence an individual's warfarin dose requirement. In
      this study, we evaluated allele frequencies and effects of CYP2C9 and VKORC1 on
      warfarin response during initial anticoagulation therapy in Korean patients. We
      enrolled patients who had initiated warfarin therapy and undergone PT-INR testing
      at least three times within the first month of anticoagulation therapy. All the
      participating patients were tested for the detection of CYP2C9*3 (c.1075A>C) and
      VKORC1-1639G>A. A melting-curve analysis after real-time PCR was performed using
      CYP2C9*3 and VK1639 genotyping kits (Idaho Technology, US). A total of 37
      patients were enrolled in this study. CYP2C9*1/*1 (87%) and VKORC1-1639AA
      genotypes (89%) were predominant in Korea. The CYP2C9*3 and VKORC1-1639G alleles
      were found in five (13%) and four patients (11%), respectively. Patients with the
      CYP2C9*3 allele received a lower warfarin dose (P = 0.018) and tended to show
      more rapid PT-INR increase than CYP2C9*1/*1 genotype. Patients with the VKORC1
      1639G allele nonsignificantly received higher warfarin dose than those without.
      The CYP2C9*3 and VKORC1-1639G alleles influenced warfarin response during the
      first month of anticoagulation therapy. Considering these results, CYP2C9 and
      VKORC1 genotyping can be an useful tool to estimate initial warfarin dose and
      frequency of PT-INR monitoring during the first month of anticoagulation therapy.

PMID- 21713379
TI  - Direct anterior approach for total hip arthroplasty using the fracture table.
AB  - Total hip arthroplasty is a successful procedure for treatment of painful hip
      arthritides. A large volume of literature is devoted to the patient outcomes and
      complication profiles of the commonly used surgical approaches to help refine the
      technique, enhance patient function, and limit cost and patient morbidity. The
      direct anterior approach has been reported using a fracture table to promote
      surgical exposure to the proximal femur. This technique is described herein with
      attention paid to the technical points which facilitate surgical exposure,
      patient safety, and functional outcome. Following a literature review of recent
      reports using this procedure are reviewed in context of the reported
      complications. The results show the direct anterior approach using a fracture
      table performed by experienced surgeons is an effective technique which provides
      early postoperative function and reduces the risk of dislocation.

PMID- 21713380
TI  - Inhibitory effect of phytoglycoprotein (38 kDa) on expression of matrix
      metalloproteinase-9 in 12-O-tetradecanoylphorbol-13-acetate-treated HepG2cells.
AB  - Tumor metastasis is one of the main causes of death for patients with malignant
      tumors. Matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion
      and metastasis of various cancer cells. Firstly, glycoprotein isolated from
      Styrax japonica Siebold et al. Zuccarini (SJSZ) has a molecular weight with 38
      kDa and consists of carbohydrate (57.64%) and protein (42.35%). In the
      composition of SJSZ glycoprotein, carbohydrate mostly consists of glucose
      (28.17%), galactose (21.85%) and mannose (2.62%) out of 52.64%, respectively. the
      protein consists of Trp (W, 7.01%), Pro (P, 6.72%), and Ile (I, 5.42%) out of
      42.35% as three major amino acids, while total amount of other amino acids is
      23.20%. The present study was designed to demonstrate whether or not SJSZ
      glycoprotein prevents the activity of MMP-9 as a metastasis factor against 12-O
      tetradecanoylphorbol-13-acetate (TPA). The study evaluated intracellular ROS and
      the phosphorylation of mitogen-activated protein kinases (MAPKs: extracellular
      signal-regulated kinase [ERK], stress-activated protein kinase/c-Jun N-terminal
      kinase [SAPK/JNK] and the p38 MAPK), the activities of transcriptional factors
      (nuclear factor [NF]-kappaB and activator protein [AP]-1), cyclooxygenase (COX)
      2, inducible nitric oxide synthase (iNOS), and MMP-9 in TPA-induced HepG2 cells
      using the Western blotting analysis, EMSA and gelatin zymography. The results
      showed that SJSZ glycoprotein (50 MUg/ml) suppressed the production of
      intracellular ROS and the phosphorylation of ERK, JNK and p38 MAPK, as well as
      the activities of transcriptional factors (NF-kappaB and AP-1), COX-2, iNOS, and
      MMP-9 in TPA-induced HepG2 cells. Taking the aforementioned results into account
      together, this present study suggested that SJSZ glycoprotein might be a potent
      anti-metastatic agent that suppresses MMP-9 enzymatic activity via the NF-kappaB
      and AP-1 signaling pathway.

PMID- 21713381
TI  - Quantification of cAMP and cGMP analogs in intact cells: pitfalls in enzyme
      immunoassays for cyclic nucleotides.
AB  - Immunoassays are routinely used as research tools to measure intracellular cAMP
      and cGMP concentrations. Ideally, this application requires antibodies with high
      sensitivity and specificity. The present work evaluates the cross-reactivity of
      commercially available cyclic nucleotide analogs with two non-radioactive and one
      radioactive cAMP and cGMP immunoassay. Most of the tested cyclic nucleotide
      analogs showed low degree competition with the antibodies; however, with Rp
      cAMPS, 8-Br-cGMP and 8-pCPT-cGMP, a strong cross-reactivity with the
      corresponding cAMP and cGMP, respectively, immunoassays was observed. The
      determined EIA-binding constants enabled the measurement of the intracellular
      cyclic nucleotide concentrations and revealed a time- and lipophilicity-dependent
      cell membrane permeability of the compounds in the range of 10-30% of the
      extracellular applied concentration, thus allowing a more accurate prediction of
      the intracellular analog levels in a given experiment.

PMID- 21713382
TI  - Lack of enantiomeric influence on the brain cytoprotective effect of ibuprofen
      and flurbiprofen.
AB  - R(-) enantiomers of the 2-arylpropionic acid derivatives ibuprofen and
      flurbiprofen weakly inhibit cyclooxygenase (COX) activity. However, a possible
      cytoprotective effect has been proposed. The aim of the study is to investigate
      the possible mechanism of this effect. An in vitro hypoxia-reoxygenation model in
      rat brain slices was used (n=6 rats per group). After reoxygenation, we measured
      LDH efflux (neuronal death), brain prostaglandin E(2) (PGE(2)) concentration,
      interleukins (IL)-1beta and 10, oxidative and nitrosative stress (lipid
      peroxides, glutathione, 3-nitrotyrosine, and nitrites/nitrates). Anti-COX
      activity was measured in human whole blood. Racemic, R(-), and S(+) enantiomers
      of ibuprofen and flurbiprofen were tested. All compounds had a cytoprotective
      effect with IC(50) values in the range of 10(-5) M. R(-) enantiomers did not
      significantly inhibit brain PGE(2). The concentration of IL-1beta was reduced by
      53.1% by the racemic form, 30.6% by the S(+) and 43.2% by the R(-) enantiomer of
      ibuprofen. The IL-10 concentration increased significantly only with S(+)
      flurbiprofen (33.1%) and R(-)-flurbiprofen (26.1%). Lipid peroxidation was
      significantly reduced by all three forms of flurbiprofen. Nitrite + nitrate
      concentrations were reduced by racemic, S(+), and R(-)-flurbiprofen.
      Peroxynitrite formation (3-nitrotyrosine) was significantly reduced by racemic
      and S(+)-ibuprofen. COX inhibition is not the main mechanism of cytoprotection
      for these compounds. Their influence on inflammatory mediators and oxidative and
      nitrosative stress could account for the potential cytoprotective effect of R(-)
      enantiomers.

PMID- 21713383
TI  - Protein-protein interactions: a mechanism regulating the anti-metastatic
      properties of Nm23-H1.
AB  - Nm23-H1, also known as NDPK-A, was the first of a class of metastasis suppressor
      genes to be identified. Overexpression of Nm23-H1 in metastatic cell lines
      (melanoma, breast carcinoma, prostate, colon, hepatocellular, and oral squamous
      cell carcinoma) reduced cell motility in in vitro assays and metastatic potential
      in xenograft models, without a significant effect on primary tumor size. The
      mechanism of Nm23-H1 suppression of metastasis, however, is incompletely
      understood. Nm23-H1 has been reported to bind proteins, including those in small
      G-protein complexes, transcriptional complexes, the Map kinase, the TGF-beta
      signaling pathways and the cytoskeleton. Evidence supporting these associations
      is presented together with evidence of resultant biochemical and phenotypic
      consequences of association. Cumulatively, the data suggest that part of the anti
      metastatic function of Nm23-H1 lies in pathways that it interrupts via binding
      and inactivation of proteins.

PMID- 21713384
TI  - The HIV reverse transcriptase inhibitor tenofovir induces cell cycle arrest in
      human cancer cells.
AB  - Selected HIV drugs, either of the protease inhibitor type or the nucleoside
      antagonist type, have been shown to exert tumoricidal effects. Here, we show that
      the HIV reverse transcriptase inhibitor Truvada, a combination drug of the
      cytidine analogue emtricitabine and the adenosine analogue tenofovir, induces DNA
      damage and cell cycle arrest in human cancer cells. Phosphorylation of the DNA
      repair enzyme H2AX by emtricitabine/tenofovir indicated that it interfered with
      the integrity of the DNA and replication machinery in human cancer cells. Long
      term incubation of cancer cells with emtricitabine/tenofovir caused the formation
      of multi-nuclear giant cells, further indicating DNA replication problems. When
      tested as single agents, the anti-tumoral activity of emtricitabine/tenofovir was
      predominantly caused by tenofovir, although the combination with emtricitabine
      enhanced its effect on cancer cells. Combined with established anti-cancer drugs,
      emtricitabine/tenofovir was preferentially found to enhance the cytotoxic effect
      of doxorubicin, a promising drug for the treatment of relapsed, chemoresistant
      cancer. These results show that especially the adenosine analogue tenofovir could
      be used to interfere with the proliferation machinery of human cancer cells and
      to be applied for chemosensitization of cancer cells to already established DNA
      interacting drugs.

PMID- 21713386
TI  - Changes in microbial populations and enzyme activities during nitrogen
      biodegradation of domestic sewage treatment in the Subsurface Wastewater
      Infiltration System (SWIS).
AB  - During the process of domestic sewage treatment in the Subsurface Wastewater
      Infiltration System (SWIS), changes in the microbial populations (nitrifying and
      denitrifying bacteria) and enzyme activities (urease, nitrate reductase and
      nitrite reductase) involved in the nitrogen removal process were evaluated over a
      2-year period. The results showed nitrifying bacteria number declined with depths
      increasing, while denitrifying bacteria increased, both of which increased nearer
      the inlet. The depth for nitrate reductase activity from high to low in sequence
      was 0.3, 0.5, 0.7, 0.9 and 1.1 m. For nitrite reductase, the sequence was 0.5,
      0.3, 0.7, 0.9 and 1.1 m. Urease and nitrite reductase activities were in positive
      correlation with the total nitrogen removal efficiency, with correlation
      coefficients 0.8662 and 0.9140, respectively and could be alternative to monitor
      the nitrogen biodegradation process in SWIS.

PMID- 21713385
TI  - Yin and Yang of hypothalamic insulin and leptin signaling in regulating white
      adipose tissue metabolism.
AB  - Fatty acids released from white adipose tissue (WAT) provide important energy
      substrates during fasting. However, uncontrolled fatty acid release from WAT
      during non-fasting states causes lipotoxicity and promotes inflammation and
      insulin resistance, which can lead to and worsen type 2 diabetes (DM2). WAT is
      also a source for insulin sensitizing fatty acids such as palmitoleate produced
      during de novo lipogenesis. Insulin and leptin are two major hormonal adiposity
      signals that control energy homeostasis through signaling in the central nervous
      system. Both hormones have been implicated to regulate both WAT lipolysis and de
      novo lipogenesis through the mediobasal hypothalamus (MBH) in an opposing fashion
      independent of their respective peripheral receptors. Here, we review the current
      literature on brain leptin and insulin action in regulating WAT metabolism and
      discuss potential mechanisms and neuro-anatomical substrates that could explain
      the opposing effects of central leptin and insulin. Finally, we discuss the role
      of impaired hypothalamic control of WAT metabolism in the pathogenesis of insulin
      resistance, metabolic inflexibility and type 2 diabetes.

PMID- 21713387
TI  - Comparison of nitrofen uptake via water and food and its distribution in tissue
      of common carp, Cyprinus carpio L.
AB  - Carp (Cyprinus carpio L.) were exposed to nitrofen (NIP) by different routes (via
      water or food) to compare bioaccumulation parameters and tissue distribution. The
      bioconcentration factor of NIP was 5,100, and the lipid-corrected
      biomagnification factor was 0.137. Growth-corrected elimination half lives were
      2.1-3.0 days via aqueous exposure and 2.7-2.9 days via dietary exposure. From
      either uptake route, the tissue distribution of NIP was highest in the head,
      followed by muscle, viscera, dermis, digestive tract and hepatopancreas, which
      was highly correlated with the tissue lipid content. We conclude that the uptake
      route has no influence on tissue distribution of NIP and that the accumulation
      potential in tissues depends on the lipid content.

PMID- 21713388
TI  - PM 2.5 and PAH concentrations in urban atmosphere of Tiruchirappalli, India.
AB  - Airborne PM 2.5 and polycyclic aromatic hydrocarbons (PAHs) bound to it were
      determined from March 2009 to February 2010 at different locations in
      Tiruchirappalli City, Southern India using fine particulate sampler and high
      performance liquid chromatography. Average ?9 PAHs concentrations at four
      sampling stations were 333.7, 202.6, 265.9, and 232.7 ng/m(3), respectively.
      Highest concentration of PAHs was observed during northeast monsoon season (301.5
      ng/m(3)) and lowest in southwest monsoon (216 ng/m(3)). Low and medium molecular
      weight PAHs such as phenanthrene, anthracene, benzo(a)anthracene and chrysene
      were observed in all seasons. Principal compound analysis revealed gasoline and
      diesel vehicular emissions as major sources for PAHs compounds.

PMID- 21713389
TI  - Curcumin decreases survival of Hep3B liver and MCF-7 breast cancer cells: the
      role of HIF.
AB  - BACKGROUND: Curcumin, a commonly used spice, affects the activities of cytokines,
      enzymes, and transcription factors that are linked to inflammation. Furthermore,
      curcumin has been assigned tumor growth inhibiting effects, possibly mediated by
      promoting hypoxia-inducible factor (HIF) degradation. HIFs are transcription
      factors that play a central role in the adaptation and response to low oxygen
      levels in metazoan cells. However, curcumin also exhibits properties of an iron
      chelator indicating its potential of inhibiting HIF-alpha prolyl hydroxylase
      (PHD) activity. METHODS: We were interested in clarifying these divergent actions
      of curcumin in due consideration of the effects on radio-therapy. Thus,
      concentration- and time-dependent effects of curcumin on HIF-alpha and -beta
      protein levels and activity in hepatoma and breast carcinoma cell cultures under
      normoxic and hypoxic conditions were studied. RESULTS: It was shown that HIF
      1alpha accumulated in normoxia after the application of higher doses of the drug.
      Curcumin proved to lower HIF-1alpha and HIF-2alpha protein levels in hypoxia. HIF
      1beta (ARNT; arylhydrocarbon nuclear translocator) protein levels and HIF
      transcriptional activity were reduced in normoxia and hypoxia after 4 h and 24 h
      incubation periods. Furthermore, curcumin treatment negatively impacted on
      clonogenic cell survival of Hep3B hepatoma and MCF-7 breast carcinoma cells.
      CONCLUSION: Effects of curcumin on cell growth and survival factor expression
      suggest its potential benefit in the treatment of cancer without a direct
      radiosensitizing influence of curcumin on these cells.

PMID- 21713390
TI  - Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in
      patients with brain oligometastases: long-term analysis.
AB  - OBJECTIVE: To verify whether the treatment of brain oligometastases with whole
      brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical
      resection results in different outcomes. METHODS: Files of patients affected by
      brain metastases submitted to surgical resection followed by WBRT (group A) or
      WBRT + SRT (group B) were retrospectively selected for this study. The two
      treatment groups were matched for the following potential prognostic factors:
      WBRT schedule, age, gender, performance status, tumor type, number of brain
      metastases, extra-cerebral metastases, and recursive partitioning analysis class
      (RPA). The outcomes of patients in both groups were evaluated in terms of
      toxicity, local control, and overall survival. RESULTS: Total of 97 patients were
      selected (56 male; 42 female) who were respectively submitted to surgical
      resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n =
      47 patients). Median follow-up was 95 months (range, 8-171 months). The 1-year
      local control rates were 46.0% and 69.0% respectively. No significant difference
      in local tumor control was observed between group A and B (p = 0.10). Median
      overall survival was 15 and 19 months in group A and B, respectively. One-year
      survival was 56.0% and 62%, respectively. No difference was observed in the two
      groups (p = 0.40). CONCLUSION: Surgery remains the main therapeutic approach in
      symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in
      one or two brain metastases smaller than 3 cm.

PMID- 21713391
TI  - Extrapulmonary small cell carcinoma: An indication for prophylactic cranial
      irradiation? A single center experience.
AB  - BACKGROUND: Information about extrapulmonary small cell carcinoma (EPSCC) is
      limited and the role of prophylactic cranial irradiation (PCI) is unknown.
      PATIENTS AND METHODS: Disease presentation and outcome of all EPSCC at our
      hospital between 1990 and 2009 were retrospectively analyzed. RESULTS: Of 30
      EPSCC, the male:female ratio was 58%:42%; 83% had a performance status of 0-2.
      Median age was 71 years (32-80). Seventeen (57%) had limited stage (LS), 13 (43%)
      extensive stage (ES). The location of the primary tumor was gastrointestinal (n =
      8), unknown (6), gynecological (6), urogenital (5), and ear nose throat (5). Four
      (13%) developed brain metastases (2 ES, 2 LS). In ES, first line chemotherapy
      (CT) was given in 85%, mostly platinum-etoposide (64%). Response rate was 90%. In
      LS, CT and radiotherapy (RT) +/- resection resulted in persistent remissions in
      67% of patients. Median survival was 16 months (1-107 months), 18 months (1-107
      months), and 9 months (0.4-25 months) for LS + ES, LS, and ES, respectively.
      Weight loss >=5 % and ECOG performance status 3 + 4 were associated with poorer
      survival (p < 0.001 and p < 0.01, respectively). CONCLUSION: The incidence of
      brain metastases was relatively low (13%). More studies are necessary, before
      routinely offering PCI to patients with EPSCC. Best survival outcomes in LS were
      achieved with multimodality treatment including CT and RT. Prognosis was poor in
      patients with ES.

PMID- 21713392
TI  - Feasibility of tomotherapy for Graves' ophthalmopathy: Dosimetry comparison with
      conventional radiotherapy.
AB  - PURPOSE: To compare the dosimetry of tomotherapy and the conventional half-beam
      technique (HBT) or non-split beam technique (NSBT) for target coverage and
      radiation dose to the lacrimal glands and lens. PATIENTS AND METHODS: A
      retrospective review of 7 patients with Graves' ophthalmopathy who had
      radiotherapy because of disease progression on high steroid dose is reported: 3
      patients were treated with tomotherapy and 4 patients with HBT. RESULTS: Compared
      to HBT, tomotherapy may provide better target coverage and significant reduction
      of radiation dose to the lacrimal glands and a higher dose to the lens. The NSBT
      improved target coverage but resulted in significantly higher doses to the lens
      and lacrimal glands. CONCLUSION: Tomotherapy may provide better coverage of the
      target volume and may be more effective in reducing severe exophthalmos compared
      to the conventional radiotherapy technique.

PMID- 21713393
TI  - CT-myelography for high-dose irradiation of spinal and paraspinal tumors with
      helical tomotherapy: revival of an old tool.
AB  - BACKGROUND AND PURPOSE: High-dose irradiation or reirradiation of spinal and
      paraspinal tumors is a challenge particularly in the presence of metal artifacts
      after surgery. Image-guided advanced intensity-modulated radiotherapy delivers
      high-dose radiation to the tumor sparing the spinal cord. Precise delineation of
      the spinal cord is necessary treating para- and intraspinal tumors with a
      sufficient dose. PATIENTS AND METHODS: The use of myelo-CT was evaluated in 23
      patients with spinal and paraspinal tumors. All patients had had previous surgery
      with metal implants in the radiation area. All patients had an indication for
      high-dose irradiation. Treatment planning was performed using nonenhanced and
      contrast-enhanced myelo-CT in the same position and immobilization and both CT
      scans were matched. Treatment was performed by using a tomotherapy treatment
      unit. RESULTS: Contouring of the myelon in all slices of the myelo-CT was
      possible in 20 of 23 patients. All these patients were treated with doses of
      median 69.4 Gy in 2 Gy/1.8 Gy single doses using daily image guidance. One
      patient received an integrated boost with a TD/SD of 70/2.3 Gy. No side effects
      have been observed so far during a median follow-up of 15.5 months. No separation
      between tumor and myelon could be observed in 3 patients. CONCLUSION: Myelo-CT
      offers a distinct delineation of the myelon and the paraspinal tumor in case of
      artifacts due to metal implants after surgery. Using this tool in combination
      with advanced image guidance and IMRT techniques, patients with relatively
      radioresistent paraspinal tumors might have the chance of improved local control
      using higher target doses.

PMID- 21713394
TI  - Clinical comparison of dose calculation using the enhanced collapsed cone
      algorithm vs. a new Monte Carlo algorithm.
AB  - PURPOSE: Comparison of the dosimetric accuracy of the enhanced collapsed cone
      (eCC) algorithm with the commercially available Monte Carlo (MC) dose calculation
      for complex treatment techniques. MATERIAL AND METHODS: A total of 8 intensity
      modulated radiotherapy (IMRT) and 2 stereotactic body radiotherapy (SBRT) lung
      cases were calculated with eCC and MC algorithms with the treatment planning
      systems (TPS) Oncentra MasterPlan 3.2 (Nucletron) and Monaco 2.01 (Elekta/CMS).
      Fluence optimization as well as sequencing of IMRT plans was primarily performed
      using Monaco. Dose prediction errors were calculated using MC as reference. The
      dose-volume histrogram (DVH) analysis was complemented with 2D and 3D gamma
      evaluation. Both algorithms were compared to measurements using the Delta4 system
      (Scandidos). RESULTS: Recalculated with eCC IMRT plans resulted in lower planned
      target volume (PTV) coverage, as well as in lower organs-at-risk (OAR) doses up
      to 8%. Small deviations between MC and eCC in PTV dose (1-2%) were detected for
      IMRT cases, while larger deviations were observed for SBRT (up to 5%). Conformity
      indices of both calculations were similar; however, the homogeneity of the eCC
      calculated plans was slightly better. Delta4 measurements confirmed high
      dosimetric accuracy of both TPS. CONCLUSION: Mean dose prediction errors < 3% for
      PTV suggest that both algorithms enable highly accurate dose calculations under
      clinical conditions. However, users should be aware of slightly underestimated
      OAR doses using the eCC algorithm.

PMID- 21713395
TI  - Randomized clinical trial of postoperative strontium-90 radiation therapy for
      pterygia: treatment using 30 Gy/3 fractions vs. 40 Gy/4 fractions.
AB  - BACKGROUND AND PURPOSE: Postoperative adjuvant treatment with strontium-90
      radiation therapy (RT) is a proven technique for reducing the recurrence of
      pterygium. This randomized trial was conducted to evaluate whether a total dose
      of 40 Gy provides a better local control rate than a total dose of 30 Gy for
      surgically resected pterygia. PATIENTS AND METHODS: A single institutional
      randomized trial was conducted. Between 1999 and 2003, 74 pterygia in 71 patients
      were randomly allocated to 30 Gy/3 fractions/15 days (arm A) or to 40 Gy/4
      fractions/22 days (arm B). Only primary pterygia for which RT could be started
      within 3 days of surgical resection were included. Postoperative RT was given by
      a strontium-90 eye applicator, and a dose of 10 Gy per fraction was delivered in
      weekly fractions (day 1, 8, 15, 22). RESULTS: Of the 74 pterygia treated, 73 in
      70 patients were analyzed. Of the 73 pterygia, 41 were allocated to arm A, and
      the remaining 32 to arm B. The 2-year local control rates for arm A and arm B
      were 85% and 75%, respectively, without significant difference. No serious acute
      and late complications were noted in either arm. CONCLUSION: Our new standard
      fractionation for postoperative RT for pterygia is 30 Gy/3 fractions.

PMID- 21713396
TI  - Respiratory-induced prostate motion: characterization and quantification in
      dynamic MRI.
AB  - BACKGROUND AND PURPOSE: To investigate prostate movement during deep breathing
      and contraction of abdominal musculature by means of dynamic MRI and analyze
      implications for image-guided radiotherapy of prostate cancer. PATIENTS AND
      METHODS: A total of 43 patients and 8 healthy volunteers were examined with MRI.
      Images during deep respiration and during contraction of abdominal musculature
      (via a coughing maneuver) were obtained with dynamic two-dimensional (2D)
      balanced SSFP; 3 frames/s were obtained over an acquisition time of 15 s. Images
      were acquired in sagittal orientation to evaluate motion along both the
      craniocaudal (cc)-axis and anteroposterior (ap)-axis. Prostate motion was
      quantified semi-automatically using dedicated software tools. RESULTS:
      Respiratory induced mean cc-axis displacement of the prostate was 2.7 +/- 1.9
      (SD) mm (range, 0.5-10.6 mm) and mean ap-axis displacement 1.8 +/- 1.0 (SD) mm
      (range, 0.3-10 mm). In 69% of the subjects, breathing-related prostate movements
      were found to be negligible (< 3 mm). The prostate displacement for abdominal
      contraction was significantly higher: mean cc-axis displacement was max. 8.4 +/-
      6.7 (SD) mm (range, 0.6-27 mm); mean anteroposterior movement was 8.3 +/- 7.7
      (SD) mm (range, 0.7-26 mm). CONCLUSION: Dynamic MRI is an excellent tool for
      noninvasive real-time imaging of prostate movement. Further investigations
      regarding possible applications in image-guided radiotherapy, e.g., for
      individualized planning and in integrated linac/MRI systems, are warranted.

PMID- 21713397
TI  - Reirradiation of spinal column metastases: comparison of several treatment
      techniques and dosimetric validation for the use of VMAT.
AB  - BACKGROUND: For reirradiation of spinal column metastases, intensity-modulated
      radiation therapy (IMRT) reduces the dose to the spinal cord, while allowing
      longer treatment times. We analyzed the potential of volumetric modulated arc
      therapy (VMAT) to reduce treatment time and number of monitor units (MU).
      PATIENTS AND METHODS: In CT datasets of 9 patients with spinal column metastases,
      the planned target volume (PTV) encompassed the macroscopic tumor including the
      spinal cord or medullary cone, respectively. The prescribed dose for the target
      was 40 Gy, but median spinal cord dose was intended to be < 26 Gy. We compared a
      posterior (3D-PA) static field technique, a two-field wedge technique (3D-wedge)
      and 5-/7-beam IMRT with VMAT. Conformity index (CI), homogeneity index (HI40),
      dose volume histogram (DVH) parameters, treatments delivery time (T), and MU were
      analyzed. Dosimetry was validated with EDR2-film/ionization chambers. RESULTS:
      PTV coverage was insufficient for 3D-conformal radiotherapy (3D-CRT) when spinal
      cord tolerance was respected. The IMRT approach provided excellent results but
      has the longest treatment time. VMAT produced dose distributions similar to IMRT
      with shorter treatment times (VMAT: mean 4:49 min; IMRT: mean 6:50 min) and fewer
      MU (VMAT: 785; IMRT: 860). Reduced conformity and increased homogeneity for VMAT
      when compared to IMRT were observed. An absolute deviation between measured and
      calculated dose of +0.70 +/- 3.69% was recorded. gamma-Index analysis showed an
      agreement of 91.33 +/- 3.53% for the 5%/5 mm criteria. CONCLUSION: For this
      paradigm, VMAT produces high quality treatment plans with homogeneity/conformity
      similar to static IMRT, shorter treatment times, and fewer MU. Verification
      measurements showed good agreement between calculation and delivered dose,
      leading to clinical implementation.

PMID- 21713398
TI  - Mechanism of attenuation of pro-inflammatory Ang II-induced NF-kappaB activation
      by genistein in the kidneys of male rats during aging.
AB  - Angiotensin II (Ang II), a main effector of the renin-angiotensin system, is
      recognized as a pro-inflammatory mediator on age-related vascular inflammation.
      Ang II is one of the most important oxidative stress inducer, activates the redox
      sensitive transcription factor, nuclear factor-kappaB (NF-kappaB) during aging.
      Genistein, a major component found in isoflavone, has anti-inflammatory
      activities that are often associated with its anti-oxidative activity. The
      purpose of this study is to document molecular mechanism of altered Ang II
      related NF-kappaB activation during aging and inhibitory molecular events by
      genistein regarding to age-related Ang II-induced NF-kappaB activation. At
      present, we utilized young (6 months old), old (24 months old), and genistein
      treated (2 and 4 mg/kg/day for 10 days) old rats. For our current study, we
      choose to use the kidney and rat endothelial cell line, YPEN-1 because of its
      vulnerability to age-related oxidative stress and inflammatory responsiveness.
      The results of the analysis showed that Ang II and AT1 expression increased
      during aging and that these increases were blunted by treatment with genistein.
      Furthermore, we investigated the inhibitory effects of genistein on the Ang II
      induced redox imbalance in aged rat kidneys. Genistein reduced age-related
      increases in NF-kappaB activity and NF-kappaB-dependent pro-inflammatory genes
      expression. We also determined genistein attenuated Ang II-induced NF-kappaB
      activation through its anti-oxidant activity in YPEN-1 cells. Taken together, our
      present results show that genistein has potent anti-inflammatory effect resulting
      in the attenuation of the Ang II-induced NF-kappaB activation during aging. The
      most significant new finding from this study is that genistein exerts its anti
      Ang II action during aging by suppressive effect of NF-kappaB activation. Based
      on these data, genistein may be an anti-Ang II agent that may be used in anti
      inflammatory therapies.

PMID- 21713399
TI  - Efficacy of an intensive post-induction chemotherapy regimen for adult patients
      with Philadelphia chromosome-negative acute lymphoblastic leukemia, given
      predominantly in the out-patient setting.
AB  - Intensification of chemotherapy in adults with acute lymphoblastic leukemia (ALL)
      has improved outcome. The aim of this analysis was to evaluate outcome of
      patients treated with an intensive regimen based on that used in the German
      national trials, but adapted in order to enable treatment to be given mainly on
      an out-patient basis, once complete remission (CR) had been achieved. Between
      2000 and 2007, 53 patients with Philadelphia chromosome-negative ALL (40 with B
      ALL and 13, T-ALL) received treatment. CR was achieved in 47/53 (89%), with no
      significant difference in CR rate between B- and T-ALL. At a median follow-up of
      6.3 years, 25 patients are alive, 23 (43%) in 1st CR, and 20 have relapsed. No
      patient died in CR due to treatment-related toxicity. At 5 years, overall
      survival was 50%, and disease-free survival, 53%. Thirty four of the 47 patients
      in whom CR was achieved completed therapy and are evaluable for duration of
      hospital stay and number of Day Unit attendances. The median time in hospital
      during the year of treatment was 10 weeks (range, 6-44) with no significant
      difference between patients <= vs. >30 years old. It was possible to administer
      this intensive protocol largely on an out-patient basis without compromising
      patient safety.

PMID- 21713400
TI  - Obstetric providers' knowledge, awareness, and use of CDC'S HIV testing
      recommendations and One Test. Two Lives.TM.
AB  - This study examined the impact of the Centers for Disease Control and
      Prevention's (CDC's) One Test. Two Lives.TM (OTTL) campaign on key outcomes
      related to CDC's revised HIV testing recommendations and the use of the campaign
      materials. Data from three cross-sectional surveys were used to assess the effect
      of OTTL on Obstetricians/Gynecologists' (OB/GYN) HIV knowledge and practice. A 2
      year combined sample of 500 OB/GYNs completed DocStyles, a Web-based survey for
      physicians, and 575 American College of Obstetricians and Gynecologists (ACOG)
      Fellows completed an ACOG survey. The surveys were similar in focus but did not
      contain the same items. Data were analyzed using cross-tabulations, chi(2)
      analyses, and logistic regression. There was a 20% recall of exposure to OTTL
      with DocStyles and 25% with ACOG. DocStyles respondents reporting having seen
      OTTL materials were significantly more likely to report awareness of CDC's
      recommendations [chi(2)(1) = 25.43, P < .001] and include HIV testing as a
      regular screening test for all patients [chi(2)(1) = 4.98, P < .05]. ACOG
      respondents not using the materials indicated high levels of willingness to use
      the materials-63.0 to 71.5%, depending on the material. Of the ACOG sample, 68.1%
      correctly answered the knowledge items regarding the recommendations. However, a
      significant relationship between correct knowledge and campaign exposure was not
      found. Overall, results suggest that OTTL is instrumental in raising awareness
      and implementation of the testing recommendations and plays an important role in
      facilitating HIV testing practices with obstetric providers and their patients.

PMID- 21713401
TI  - Guest editorial: tackling the problems of hematopoietic stem cell aging.

PMID- 21713402
TI  - Freshwater fish-consumption relations with total hair mercury and selenium among
      women in eastern China.
AB  - Wild fish from Qiandao Hu, a reservoir in the Zhejiang Province in eastern China,
      have increased mercury (Hg) concentrations exceeding the World Health
      Organization's (WHO) recommended guidelines. Due to the importance of freshwater
      biota in the local cuisine, dietary exposure to increased neurotoxic Hg is a
      concern in this region. An environmental hair-marker study was undertaken
      coincident with a cross-sectional epidemiologic study with 50 women age 17-46
      years living in a Qiandao Hu fishing village. Diet, occupation, and other
      possible sources of Hg were recorded by way of questionnaires. Total mercury
      (THg) and selenium (Se) concentrations were measured in human hair samples and in
      important market fish species. Fish THg and Se concentrations were increased,
      with some fish concentrations >200 ng/g THg and 500 ng/g Se (wet weight [ww]).
      However, the average hair THg was low at 0.76 +/- 0.51 MUg/g dry weight, lower
      than the WHO's no observable-adverse effect level (50 MUg/g), whereas the average
      hair Se was 1.0 MUg/g. Hair THg concentration was positively associated with the
      average mass of fish consumed weekly, indicating that fish consumption is the
      main contributor to hair THg in this geographic area. The age-related hair THg
      trend was not linear but instead demonstrated a rapid increase in THg before age
      25 years, followed by consistent concentrations in all ages after age 25 years.
      There was a positive correlation (p < 0.001) between molar Se and Hg in the hair
      samples, suggesting a possible antagonistic relation. This is the first study
      examining the relation between dietary Hg exposure and hair THg in an eastern
      China community where freshwater fish, as opposed to marine fish, dominates the
      cuisine.

PMID- 21713403
TI  - Compromised cellular responses to DNA damage accelerate chronological aging by
      incurring cell wall fragility in Saccharomyces cerevisiae.
AB  - Elevated levels of reactive oxygen species (ROS) can attack almost all cell
      components including genomic DNA to induce many types of DNA damage. In this
      study, we used Saccharomyces cerevisiae with various mutations in a biological
      network supposed to prevent deleterious effects of endogenous ROS to test the
      effect of such a network on yeast chronological aging. Our results showed that
      cells with defects in cellular antioxidation, DNA repair and DNA damage
      checkpoints displayed a mutation rate higher than that of wild-type strain.
      Moreover, the chronological life span of most mutants as determined by colony
      formation was found to be shorter than that of wild-type cells, especially for
      the mutants defective in DNA replication and DNA damage checkpoints, although the
      observed cell number was almost the same for wild-type and mutant strains. The
      mutants were finally found to be more sensitive to SDS and lysing enzyme
      treatment, and that the degree of sensitivity was correlated with their
      chronological life span.

PMID- 21713404
TI  - Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition in
      human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways.
AB  - Metastasis of tumor cells is associated with epithelial-to-mesenchymal transition
      (EMT), which is a process whereby epithelial cells lose their polarity and
      acquire new features of mesenchyme. EMT has been reported to be induced by
      transforming growth factor-beta1 (TGF-beta1), but its mechanism remains elusive.
      In this study, we performed a study to investigate whether PI3K/Akt and
      MAPK/Erk1/2 signaling pathways involved in EMT in the human lung cancer A549
      cells. The results showed that after treated with TGF-beta1 for 48 h, A549 cells
      displayed more fibroblast-like shape, lost epithelial marker E-cadherin and
      increased mesenchymal markers Vimentin and Fibronectin. Moreover, TGF-beta1
      induced EMT after 48 h was accompanied by increased of cell migration and change
      of Akt and Erk1/2 phosphorylation. In addition, EMT was reversed by PI3K
      inhibitor LY294002 and MEK1/2 inhibitor U0126, which suggested that A549 cells
      under stimulation of TGF-beta1 undergo a switch into mesenchymal cells and
      PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-beta1-induced
      EMT of A549 cells.

PMID- 21713405
TI  - Characterization of the expression profile of calpain-3 (CAPN3) gene in chicken.
AB  - Calpain-3 is a skeletal muscle-specific protease and participates in the
      regulation of myogenesis. In this study, we quantified the expression of calpain
      3 (CAPN3) mRNA in a Chinese local chicken breed (Sichuan Mountainous Black-boned
      chicken [MB]), to discern the tissue and ontogenic expression pattern. Meanwhile,
      we compared the CAPN3 mRNA expression pattern in MB chicken at 10 weeks with a
      commercial meat type chicken line (S01) of the same age to identify the unique
      expression pattern under different genetic background. A real time quantitative
      PCR (qRT-PCR) assay was developed for an accurate measurement of its expression
      in various tissues from chickens at different ages (0, 2, 4, 6, 8, 10, and 12
      weeks). Expression of the CAPN3 mRNA was detected in the selected tissues,
      regardless of age. The breast muscle and leg muscle tissues had a significantly
      higher expression than the other tissues from the same individual (P < 0.01).
      Overall, the CAPN3 mRNA level exhibited a "rise-decline" developmental change in
      detected tissues except for brain. The S01 chicken had a higher expression of the
      CAPN3 mRNA in detected tissues than the MB chicken at 10 weeks. The present
      expression data of chicken CAPN3 gene may provide some information to shed light
      on the tissue and ontogenic expression pattern during chicken development.

PMID- 21713406
TI  - Association between two single nucleotide polymorphisms at corresponding microRNA
      and schizophrenia in a Chinese population.
AB  - Numerous linkage and association studies have been performed to identify genetic
      predispositions to schizophrenic (SCZ) in different populations, but its genetic
      basis remains unclear. Some findings may provide a clue in understanding the
      association between abnormal immunity and SCZ. MicroRNA (miRNA) involves in
      regulating both schizophrenic and immunity as previous reported. And single
      nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics,
      resulting in functional and/or phenotypic changes. So two SNPs (hsa-pre-mir-146a
      rs2910164 G>C and hsa-mir-499 rs3746444 T>C) at two miRNAs, were genotyped to
      demonstrate their association with susceptibility to SCZ. Polymorphisms were
      analyzed among 268 Chinese schizophrenic patients and 232 healthy controls by PCR
      RFLP and validated by sequencing. No association was found between the two
      polymorphisms and SCZ either in cases or in controls. SCZ patients with family
      history showed significant increase of the G allele frequency of rs2910164 in
      comparison to those without (P = 0.018). The CC genotype frequency of rs3746444
      was also higher in the patients having hallucinations than those without
      hallucinations (P = 0.012). In addition, patients carrying CC genotype of
      rs3746444 were more likely to be lack of motivation in comparison to normal
      controls (P = 0.042). Allele and genotype frequency of rs2910164 showed no
      significant difference between patients and normal subjects or between patients
      with and without clinical variables. Although patients carrying CC genotype of
      rs3746444 were found to be more likely to develop hallucination and individuals
      carrying C allele to lack motivation, there is lacking association between SCZ
      and the two SNPs at miRNAs, which may regulate immune response.

PMID- 21713407
TI  - Association of interleukin 4 VNTR polymorphism and HIV/AIDS in a north Indian
      seropositive patients.
AB  - Despite different efforts made to intervene with the deadly nature of HIV/AIDS,
      all attempts remained unsuccessful due to complexity of the viral host
      interactions. The solution to HIV-1 pandemic is still to come, thus to assist the
      efforts being made to intervene with the deadly nature of the virus, different
      factors responsible for the disease burdens have to be looked into a systematic
      manner. As a result, the present study aimed to find out the association of IL-4
      VNTR polymorphism with HIV-1 susceptibility and rate of disease progression.
      Three hundred cases and an equal number of sex and age matched controls were
      included for this study. The polymerase chain reaction assay was utilized to
      genotype IL-4 VNTR. The results of this study showed statistically significant
      variation among cases and controls in the distribution of the Rp2/Rp2 genotype
      (OR = 0.36, 95% CI = 0.18-0.69; P value = 0.0014) indicating, thereby, a
      possibility of reduced risk of HIV-1 susceptibility. Thus, Rp2/Rp2 genotype of
      the IL-4 might have a role to play in reducing risk of HIV-1 susceptibility among
      a north Indian population.

PMID- 21713408
TI  - Diagnosis of Chenopodium album allergy with a cocktail of recombinant allergens
      as a tool for component-resolved diagnosis.
AB  - Chenopodium album pollen is one of the main sources of pollen allergy in desert
      and semi-desert areas and contains three identified allergens, so the aim of this
      study is comparison of the diagnostic potential of C. album recombinant allergens
      in an allergenic cocktail and C. album pollen extract. Diagnostic potential of
      the allergenic cocktail was investigated in 32 individuals using skin prick test
      and obtained results were compared with the acquired results from C. album pollen
      extract. Specific IgE reactivity against the pollen extract and allergenic
      cocktail was determined by ELISA and western blotting tests. Inhibition assays
      were performed for the allergenic cocktail characterization. The exact
      sensitization profile of all patients was identified which showed that 72, 81 and
      46% of allergic patients had IgE reactivity to rChe a 1, rChe a 2 and rChe a 3,
      respectively. Almost all of C. album allergic patients (30/32) had specific IgE
      against the allergenic cocktail. In addition, there was a high correlation
      between IgE levels against the allergenic cocktail and IgE levels against the
      pollen extract. The allergenic cocktail was able to completely inhibit IgE
      binding to natural Che a 1, Che a 2 and Che a 3 in C. album extract. In addition,
      positive skin test reactions were seen in allergic patients that tested by the
      allergenic cocktail. The reliable results obtained from this study confirmed that
      the allergenic cocktail with high diagnostic potential could be replaced with
      natural C. album allergen extracts in skin prick test and serologic tests.

PMID- 21713409
TI  - Differential expression of microRNA patterns in planarian normal and regenerative
      tissues.
AB  - MicroRNAs (miRNAs) are ~22-nt small non-coding RNAs that regulate the expression
      of specific target genes in many eukaryotes. miRNAs have been shown to play
      important roles in stem cell maintenance, cell fate determination, and
      differentiation. Planarians are capable of regenerating entire body plans from
      tiny fragments; this regenerative capacity is facilitated by a population of
      pluripotent stem cells known as neoblasts. Planarians have been a classic model
      system for the study of many aspects of stem cell biology. However, very limited
      knowledge on miRNA involved in this regulatory mechanism exists. This study
      profiles the expression of miRNAs in the normal and regenerative tissues of
      planarians using miRCURY LNA array technology. Thirteen miRNAs showed significant
      differences in expression between these two tissues. To further confirm our
      results, we examined the expression of two miRNAs by qRT-PCR. Results show that
      some known miRNAs may play key roles in the regulatory mechanisms of
      regeneration. Our findings can be utilized in future research on miRNA function.

PMID- 21713410
TI  - Computer-assisted three-dimensional reconstruction of the fetal pancreas
      including the supplying arteries according to immunohistochemistry of pancreatic
      polypeptide.
AB  - PURPOSE: Computer-assisted three-dimensional reconstruction of the fetal human
      pancreas was prepared to reconsider topographical relation between the
      dorsal/ventral anlagen and the vascular supply. METHODS: Tissue sections from the
      upper abdominal viscera of three fetuses were examined. Sections were
      immunohistochemically stained to determine pancreatic polypeptide expression, a
      marker of the ventral pancreas. RESULTS: The immunohistochemical findings were
      used to create three-dimensional computer-assisted reconstructions to identify
      pancreatic arteries. The narrowest part of the pancreas, or the neck,
      corresponding to a part of the dorsal pancreas, was located on the left side of
      the common bile duct, portal vein and gastroduodenal artery (GDA). The posterior
      arterial arcade accompanied the ventral pancreas, whereas the anterior arcade did
      not. In contrast to the GDA, the splenic artery was clearly separated from the
      neck in fetuses. The GDA appears to be the primary and stable arterial supply for
      the neck of the pancreas. CONCLUSIONS: This observation may have implications for
      the preservation of the neck with the GDA during pancreaticoduodenectomy for
      benign and low-grade malignant diseases.

PMID- 21713411
TI  - Quercitrin a bioflavonoid improves the antioxidant status in streptozotocin:
      induced diabetic rat tissues.
AB  - Quercitrin, a bio flavonoid, was investigated for its antioxidant potential in
      streptozotocin (STZ)-induced diabetic rats. Rats were induced diabetic by a
      single intraperitoneal injection of streptozotocin (50 mg/kg). The levels of
      fasting plasma glucose and insulin were estimated. Lipid peroxidative products
      and antioxidants were estimated in pancreas, liver, and kidney. Histopathological
      studies were carried out in these tissues. A significant (P < 0.05) increase in
      the levels of fasting plasma glucose and lipid peroxidative products
      (thiobarbituric acid reactive substances and lipid hydroperoxides) and a
      significant (P < 0.05) decrease in plasma insulin, enzymic antioxidants
      (superoxide dismutase, catalase, glutathione peroxidase, and glutathione
      reductase), and nonenzymic antioxidants (reduced glutathione, vitamin C, and E)
      in diabetic pancreas, liver, and kidney were observed. Oral administration of
      quercitrin (30 mg/kg) for a period of 30 days significantly (P < 0.05) decreased
      fasting plasma glucose, increased insulin levels, and improved the antioxidant
      status of diabetic rats by decreasing lipid peroxidative products and increasing
      enzymic and nonenzymic antioxidants. Normal rats treated with quercitrin (30
      mg/kg) showed no significant (P < 0.05) effect on any of the parameters studied.
      Histopathological studies of the pancreas, liver, and kidney showed the
      protective role of quercitrin. Thus, our study clearly shows that quercitrin has
      antioxidant effect in STZ-induced experimental diabetes.

PMID- 21713412
TI  - Antibodies to citrullinated protein antigens (ACPAs): clinical and
      pathophysiologic significance.
AB  - Antibodies to citrullinated protein antigens (ACPAs) are highly specific for
      rheumatoid arthritis (RA) and are useful in the diagnosis of RA as well as the
      prediction of the course and outcomes of disease. Multiple methodologies exist
      for measuring ACPAs, including the widely available tests for anticyclic
      citrullinated peptide antibodies and for antibodies to mutated/modified
      citrullinated vimentin. These methodologies overall have similar diagnostic
      accuracies for RA, although there is some variability. The discovery of ACPAs and
      the biology of citrullination have also led to important advances in the
      understanding of the pathophysiology and development of RA, especially regarding
      the relationship between potential genetic and environmental risk factors for RA.
      Going forward, research into autoimmunity to citrullinated proteins may help
      identify the specific etiology of RA and provide approaches for the prediction of
      future risk of disease, and ultimately prevention of RA.

PMID- 21713413
TI  - Surgical repair of the distal biceps brachii tendon: a comparative study of three
      surgical fixation techniques.
AB  - PURPOSE: Several fixation techniques exist to repair the distal biceps brachii
      tendon. We aimed to evaluate the clinical and functional outcomes after distal
      biceps tendon repair using three different fixation techniques. METHODS: A total
      of 54 patients were included in the study and were available for follow-up (mean,
      30.7 months; SD 18.6). Surgery was performed using a single-incision approach
      with Corkscrews or Mitek suture anchors or with a two-incision exposure using
      transosseous sutures. The patients were evaluated with range of motion (ROM)
      measurements for flection/extension and pronation/supination as well as
      Disabilities of Arm Shoulder and Hand (DASH) scores. Furthermore, the duration of
      surgery and the length of hospital stay as well as the complication rate were
      analyzed. RESULTS: Fifty-four out of 73 patients were available after a mean
      follow-up time of 30.7 months (SD 18.6) for clinical evaluation. There was no
      statistical significant difference between the three groups comparing the mean
      DASH score, the length of hospital stay, the duration of surgery, or the ROM. The
      most common complication was neurapraxia, with 6 cases. All 3 reruptures were
      registered in the Mitek anchors group. Two patients in the Mitek anchors group
      required an open arthrolysis due to stiffness of the elbow. CONCLUSIONS: In
      summary, we achieved good clinical and functional results after surgical repair
      of the distal biceps tendon using Corkscrews, Mitek anchors, or transosseous
      sutures. The results conferred by Corkscrews were comparable to the other
      techniques, justifying their use.

PMID- 21713414
TI  - Mechanism of intermolecular hydroacylation of vinylsilanes catalyzed by a
      rhodium(I) olefin complex: a DFT study.
AB  - Density functional theory (DFT) was used to investigate the Rh(I)-catalyzed
      intermolecular hydroacylation of vinylsilane with benzaldehyde. All intermediates
      and transition states were optimized completely at the B3LYP/6-31G(d,p) level
      (LANL2DZ(f) for Rh). Calculations indicated that Rh(I)-catalyzed intermolecular
      hydroacylation is exergonic, and the total free energy released is -110 kJ mol(
      1). Rh(I)-catalyzed intermolecular hydroacylation mainly involves the active
      catalyst CA2, rhodium-alkene-benzaldehyde complex M1, rhodium-alkene-hydrogen
      acyl complex M2, rhodium-alkyl-acyl complex M3, rhodium-alkyl-carbonyl-phenyl
      complex M4, rhodium-acyl-phenyl complex M5, and rhodium-ketone complex M6. The
      reaction pathway CA2 + R2 -> M1b -> T1b -> M2b -> T2b1 -> M3b1 -> T4b -> M4b ->
      T5b -> M5b -> T6b -> M6b -> P2 is the most favorable among all reaction channels
      of Rh(I)-catalyzed intermolecular hydroacylation. The reductive elimination
      reaction is the rate-determining step for this pathway, and the dominant product
      predicted theoretically is the linear ketone, which is consistent with
      Brookhart's experiments. Solvation has a significant effect, and it greatly
      decreases the free energies of all species. The use of the ligand Cp' (Cp' =
      C(5)Me(4)CF(3)) decreased the free energies in general, and in this case the rate
      determining step was again the reductive elimination reaction.

PMID- 21713415
TI  - In silico screening of epidermal growth factor receptor (EGFR) in the tyrosine
      kinase domain through a medicinal plant compound database.
AB  - The unregulated epidermal growth factor receptor tyrosine kinase (ErbB1-TK or
      EGFR-TK) protein is involved in the proliferation of more than 50% of all cancer
      types. The reduction of EGFR-TK activity by small or medium-sized molecules has
      been proven to be an effective treatment for cancer. There is a widespread belief
      that Chinese medicinal herbs are active against several diseases, including
      various types of cancer. In this study, 29,960 compounds from the Chemiebase
      medicinal compound database were virtually screened against the EGFR-TK using
      AutoDock4.0, GOLD and GLIDE (XP). The results revealed eight potential hits: CAS
      nos. 104096-45-9, 112649-21-5, 113866-89-0, 142608-98-8, 142608-99-9, 144761-33
      1, 155233-17-3 and 80510-05-0. These compounds have been reported to show
      anticancer activities in the literature. With the help of SiMMap and MOE
      interaction analysis, the protein-ligand interaction patterns between the
      functional groups of these compounds and the binding pocket residues were
      analyzed. Hydrogen bonding and hydrophobic forces are the main components of the
      interactions of these hits, similar to those observed for the known inhibitors
      erlotinib, gefitinib and AEE. The physicochemical filter indicates that compounds
      CAS nos. 104096-45-9 and 144761-33-1 are likely to be potential leads in the drug
      discovery process.

PMID- 21713416
TI  - Effects of manipulated herbivore inputs on nutrient flux and decomposition in a
      tropical rainforest in Puerto Rico.
AB  - Forest canopy herbivores are known to increase rates of nutrient fluxes to the
      forest floor in a number of temperate and boreal forests, but few studies have
      measured effects of herbivore-enhanced nutrient fluxes in tropical forests. We
      simulated herbivore-induced fluxes in a tropical rainforest in Puerto Rico by
      augmenting greenfall (fresh foliage fragments), frassfall (insect feces), and
      throughfall (precipitation enriched with foliar leachates) in replicated
      experimental plots on the forest floor. Background rates of greenfall and
      frassfall were measured monthly using litterfall collectors and augmented by
      adding 10* greenfall or 10* frassfall to designated plots. Throughfall fluxes of
      NH(4), NO(3) and PO(4) (but not water) were doubled in treatment plots, based on
      published rates of fluxes of these nutrients in throughfall. Control plots
      received only background flux rates for these compounds but the same minimum
      amount of distilled water. We evaluated treatment effects as changes in flux
      rates for NO(3), NH(4) and PO(4), measured as decomposition rate of leaf litter
      in litterbags and as adsorption in ion-exchange resin bags at the litter-soil
      interface. Frass addition significantly increased NO(3) and NH(4) fluxes, and
      frass and throughfall additions significantly reduced decay rate, compared to
      controls. Reduced decay rate suggests that nitrogen flux was sufficient to
      inhibit microbial decomposition activity. Our treatments represented fluxes
      expected from low-moderate herbivore outbreaks and demonstrated that herbivores,
      at these outbreak levels, increase ecosystem-level N and P fluxes by >30% in this
      tropical rainforest.

PMID- 21713417
TI  - Comparative permeabilities of the paracellular and transcellular pathways of
      corneal endothelial layers.
AB  - Layers of rabbit corneal endothelial cells were cultured on permeable inserts. We
      characterized the diffusional permeability of the cell layer to nonelectrolyte
      and charged molecules and compared the diffusional and filtration permeabilities
      of the paracellular and transcellular pathways. We determined the rates of
      diffusion of (3)H- and (14)C-labeled nonelectrolyte test molecules and estimated
      the equivalent pore radius of the tight junction. Negatively charged molecules
      permeate slower than neutral molecules, while positively charged molecules
      permeate faster. Palmitoyl-DL-carnitine, which opens tight junctions, caused an
      increase of permeability and equivalent pore radius. Diffusional water
      permeability was determined with (3)H-labeled water; the permeabilities of the
      tight junction and lateral intercellular space were calculated using tissue
      geometry and the Renkin equation. The diffusional permeability (P(d)) of the
      paracellular pathway to water is 0.57 MUm s(-1) and that of the transcellular
      path is 2.52 MUm s(-1). From the P(d) data we calculated the filtration
      permeabilities (P(f)) for the paracellular and transcellular pathways as 41.3 and
      30.2 MUm s(-1), respectively. In conclusion, the movement of hydrophilic
      molecules through tight junctions corresponds to diffusion through negatively
      charged pores (r = 2.1 +/- 0.35 nm). The paracellular water permeability
      represents 58% of the filtration permeability of the layer, which points to that
      route as the site of sizable water transport. In addition, we calculated for NaCl
      a reflection coefficient of 0.16 <= sigma(NaCl) <= 0.33, which militates against
      osmosis through the junctions and, hence, indirectly supports the electro-osmosis
      hypothesis.

PMID- 21713418
TI  - Concomitant vesicoureteral reflux and gastroesophageal reflux: an analytic cross
      sectional study.
AB  - PURPOSE: Vesicoureteral reflux (VUR) and Gastroesophageal reflux (GER) are both
      common disorders in children and could be associated with significant
      morbidities. Although they appear to be separate entities, their natural history
      and underlying pathophysiology are the same and they both tend to resolve over
      time. We aimed to appraise their concurrent occurrence and prevalence of GER in
      VUR patients to understand whether they can be considered different
      manifestations of a syndrome mainly caused by developmental delay resulting in
      dysfunction of the sphincters. METHODS: Totally, 174 children <= 2 years of age
      were enrolled and 87 of them with primary VUR constituted patients group. The
      rest of the cases with the same age and sex distribution entered control group.
      All the study population underwent ultrasonographic evaluation to detect GER.
      RESULTS: GER was more frequent in patients with primary VUR. GER was more
      prevalent in higher grades of VUR. We observed higher prevalence of GER and
      higher grades of VUR in younger infants demonstrating the tendency of both
      conditions to resolve overtime. Bilateral VUR was more prevalent among patients
      with higher grades of VUR. GER was more prevalent in patients with bilateral VUR
      and Prevalence of bilateral VUR decreased with increase in age. These findings
      show that the chance of concomitant GER and VUR is higher in children with more
      severe developmental defect of sphincters. CONCLUSIONS: Regarding the higher
      prevalence of GER among VUR patients and correlation of VUR severity with co
      occurrence of GER, besides the natural tendency of both conditions to resolve
      overtime, they may be considered parts of developmental delay syndrome of
      sphincters.

PMID- 21713419
TI  - Ancient Roman wall paintings mapped nondestructively by portable NMR.
AB  - The stratigraphies of decorated walls in ancient Herculaneum, Italy, were
      analyzed by single-sided (1)H NMR. A large version of the NMR-MOUSE(r) with a
      maximum penetration depth of 25 mm was used to map proton density profiles at
      different positions of the Mosaic of Neptune and Amphitrite showing considerable
      differences between different tesserae and the mortar bed at different times of
      the year. In the House of the Black Room, different mortar layers were observed
      on painted walls as well as different proton content in different areas due to
      different moisture levels and different conservation treatments. The proton
      density profiles of the differently treated areas indicated that one method leads
      to higher moisture content than the other. Untreated wall paintings from
      different times were profiled in a recently excavated room at the Villa of the
      Papyri showing two different types of mortar layer structures which identify two
      different techniques of preparing the walls for painting. Reflectance Fourier mid
      infrared spectroscopy and in situ X-ray fluorescence measurements complemented
      the NMR measurements and provided additional insight into the identification of
      organic coatings as well as the nature of the pigments used, respectively. The
      information acquired nondestructively by NMR is valued for elaborating
      conservation strategies and for identifying different schools of craftsmen who
      prepared the mortar supports of the wall paintings.

PMID- 21713420
TI  - HPLC-APCI-MS analysis of triacylglycerols (TAGs) in historical pharmaceutical
      ointments from the eighteenth century.
AB  - The lipid fractions of residues from historical pharmaceutical ointments were
      analysed by reversed-phase liquid chromatography coupled with atmospheric
      pressure chemical ionization and mass spectrometer detection. The residues were
      contained in a series of historical apothecary jars, dating from the eighteenth
      century and conserved at the "Aboca Museum" in Sansepolcro (Arezzo, Italy) and at
      the pharmacy of the "Real Cartuja de Valldemossa" in Palma de Majorca (Spain).
      The analytical protocol was set up using a comparative study based on the
      evaluation of triacylglycerol (TAG) compositions in raw natural lipid materials
      and in laboratory-reproduced ointments. These ointments were prepared following
      pharmaceutical recipes reported in historical treatises and used as reference
      materials. The reference materials were also subjected to stress treatments in
      order to evaluate the modification occurring in the TAG profiles as an effect of
      ageing. TAGs were successfully detected in the reproduced formulations even in
      mixtures of up to ten ingredients and after harsh degradative treatments, and
      also in real historical samples. No particular interferences were detected from
      other non-lipid ingredients of the formulations. The TAG compositions detected in
      the historical ointments indicated a predominant use of olive oil and pig adipose
      material as lipid ingredients. The detection of a high level of tristearine and
      myristyl-palmitoyl-stearyl glycerol in two of the samples suggested the presence
      of a fatty material of a different origin (maybe a ruminant). On the basis of the
      positional isomer ratio, sn-PPO/sn-POP, it was possible to hypothesize an
      exclusive use of pig fat in one sample. We also evaluated the application of
      principal component analysis of TAG profiles as an approach for the multivariate
      statistical comparison of the reference and historical ointments.

PMID- 21713421
TI  - Analysis of urinary estrogens, their oxidized metabolites, and other endogenous
      steroids by benchtop orbitrap LCMS versus traditional quadrupole GCMS.
AB  - Estrogens and other endogenous steroids are known risk markers for cancer. Gas
      chromatography (GC) with mass spectrometry (MS) has traditionally predominated
      the analysis of estrogens and other endogenous steroids, but liquid
      chromatography (LC) MS is increasingly favored. Direct comparisons of the two
      technologies have hitherto not been performed. Steroids were analyzed from 232
      urine samples of 78 premenopausal women in a blinded fashion by benchtop orbitrap
      LCMS and single quadrupole GCMS. Sixteen steroidal estrogens including oxidized
      metabolites could be analyzed by LCMS. LCMS-GCMS Spearman rank correlations of
      the major estrogens E(1), E(2), E(3), 16alpha-OHE(1), and 2-OHE(1) were very high
      (r = 0.72-0.91), and absolute concentrations also agreed (<5% difference for
      E(1), E(2), E(3), 16alpha-OHE(1)). LCMS allowed reinterrogation of the acquired
      data due to orbitrap technology, which permitted post-analysis quantitation of
      progesterone, cortisol, and cortisone (LCMS-GCMS Spearman rank correlations =
      0.80-0.84; absolute difference, <7%; n = 137). GCMS allows the measurement of a
      wide range of steroids including non-polar analytes that escape the presented
      LCMS assay. In contrast, orbitrap-based LCMS can detect more estrogens, is
      faster, less costly, allows post-data acquisition reinterrogation of certain
      analytes that had not been targeted a priori, and requires much less urine.

PMID- 21713422
TI  - Construction of osteochondral-like tissue graft combining beta-tricalcium
      phosphate block and scaffold-free centrifuged chondrocyte cell sheet.
AB  - BACKGROUND: The combination of a beta-tricalcium phosphate (betaTCP) block with a
      scaffold-free chondrocyte sheet formed by the centrifugation of chondrocytes in a
      well was investigated with the aim of constructing an osteochondral-like
      structure. METHODS: Human and porcine articular cartilage chondrocytes were
      respectively centrifuged in a 96-well plate or cell culture insert (0.32 cm(2))
      that was set in a 24-well plate, cultivated in the respective vessel for 3 weeks,
      and the cell sheets were harvested. In some cases, a cylindrical betaTCP block
      (diameter 5 mm, height 3 mm) was placed on the sheet on days 1-7. The sheet size,
      cell number, and sulfated glycosaminoglycan accumulation were determined.
      RESULTS: The use of a 96-well plate for not suspension but adhesion culture and
      the initial centrifugation of a well containing cells were crucial to obtaining a
      uniformly thick cell sheet. The glycosaminoglycan density of the harvested cell
      sheet was comparable to that of the pellet culture. An inoculum cell number of
      more than 31 * 10(5) cells tended to result in a curved cell sheet. Culture
      involving 18.6 * 10(5) cells and the 96-well plate for adhesion culture showed no
      curving of the cell sheet (thickness of 0.85 mm), and these were found to be the
      best of the culture conditions tested. The timing of the addition of a betaTCP
      block to the cell sheet (1-7 days) markedly affected the balance between the
      thickness of cell sheet parts on and in the betaTCP block. CONCLUSION:
      Centrifugation and subsequent cultivation of chondrocytes (18.6 * 10(5) cells) in
      a 96-well plate for adhesion culture led to the production of a scaffold-free
      cartilage-like cell sheet with a thickness of 0.85 mm. A combined osteochondral
      like structure was produced by putting a betaTCP block on the cell sheet. The
      thickness of the cell sheet on the betaTCP block and the binding strength between
      the cell sheet and the betaTCP block could be optimized by adjusting the inoculum
      cell number and timing of betaTCP block addition.

PMID- 21713423
TI  - The effects of systemic chemical sympathectomy on local bone loss induced by
      sciatic neurectomy.
AB  - BACKGROUND: It has been suggested that the sympathetic nervous system (SNS) is
      involved in bone metabolism and that blockade of the SNS could reduce bone loss
      and stimulate bone formation. However, the question of whether suppression of SNS
      tone could compensate for mechanical unloading-induced bone loss must be further
      clarified. The purpose of this study was to investigate whether systemically
      inhibiting sympathetic nervous system (SNS) tone could prevent bone loss from
      mechanical-inactivity-induced osteopenia. METHODS: Female Wistar rats (12 weeks
      old) were randomly assigned to three groups: the SN group (n = 10), or single leg
      sciatic neurectomy group; the SNP group (n = 12), or single leg sciatic
      neurectomy + propranolol treatment (0.5 g/L in dietary water) group; and the CON
      group (n = 10), or single leg sham-operated group. Animals were fed with
      distilled water or propranolol in water, in accordance with their group design,
      for 30 days. Histomorphometry, geometry, tissue weight, and serum markers were
      assessed. RESULTS: Propranolol-treated animals drank significantly less water,
      but did not differ in daily chow consumption or body weight gain. In
      histomorphometric analysis, the spongy bone volume ratio in proximal tibiae was
      significantly lower in the two sciatic neurectomy groups, but there was no
      difference between the SN and SNP groups. Architecture analysis showed that the
      SN group had significantly thinner trabeculae and fewer trabeculae than the CON
      group (p < 0.05), but there was no difference between the SNP and CON groups.
      There were no significant differences for tissue weight, geometric measurement,
      or serum markers assay. CONCLUSION: It was observed that blockade of the SNS
      prevented neurectomy-induced bone resorption, as demonstrated by various
      histomorphometric data, although the difference between SN and SNP did not reach
      significance. In further work it would be valuable to study possible gender, age,
      and dose-dependent efficacy of propranolol on bone metabolism.

PMID- 21713424
TI  - Cementless total hip arthroplasty for avascular necrosis of the femoral head
      following cardiac transplantation: report of two cases.

PMID- 21713425
TI  - Women with insufficient 25-hydroxyvitamin D without secondary hyperparathyroidism
      have altered bone turnover and greater incidence of vertebral fractures.
AB  - BACKGROUND: The connection of 25-hydroxyvitamin D [25(OH)D] with bone metabolism
      is reported to occur indirectly through parathyroid hormone (PTH) activity.
      However, we hypothesized that 25(OH)D insufficiency raises the risk of bone
      fracture independent of PTH, since 25(OH)D insufficiency is not always
      accompanied by hyperparathyroidism. The aim of this study was to show a direct
      association between 25(OH)D, bone turnover markers, and fractures that was
      independent of PTH. METHODS: We measured serum 25(OH)D in a group of 330
      postmenopausal osteoporotic women who did not have secondary hyperparathyroidism.
      We analyzed the effects of 25(OH)D insufficiency [25(OH)D < 20 ng/mL] on the
      expression of several bone markers, including serum bone alkaline phosphatase
      (BAP), osteocalcin (OC), urinary N-terminal telopeptide of type-I collagen and
      free deoxypyridinoline (DPD), and inorganic phosphorus (IP), as well as on the
      prevalence of vertebral fractures. RESULTS: OC/BAP ratios and IP levels were
      significantly lower and DPD was significantly higher in 25(OH)D insufficient
      patients. These effects were independent of age, PTH, and estimated glomerular
      filtration rate (eGFR). 25(OH)D insufficiency, a low OC/BAP ratio, and low IP
      were related to the presence of prior vertebral fractures independent of PTH,
      bone mineral density (BMD), and eGFR. CONCLUSIONS: We propose that 25(OH)D
      insufficiency is associated with a low OC/BAP ratio and high DPD in
      postmenopausal osteoporosis patients without hyperparathyroidism. This
      pathological condition is associated with an increased incidence of prior
      vertebral fractures independent of PTH, BMD, and eGFR.

PMID- 21713426
TI  - Lack of relationship between endothelial nitric oxide synthase gene 4b/a and T
      786C polymorphisms with preeclampsia in southeast of Iran.
AB  - PURPOSE: Preeclampsia is an important disorder of pregnancy that carries a severe
      morbidity and mortality risk for both mother and fetus. A large number of studies
      have shown that abnormalities in nitric oxide synthesis may contribute to the
      development of preeclampsia. METHODS: We examined the relationship between the
      endothelial nitric oxide synthase (eNOS) gene 4b/a and T-786C polymorphisms with
      preeclampsia (PE) in 123 preeclamptic pregnant women and 142 healthy pregnant
      women in the southeast of Iran. RESULTS: Our findings indicate that the 4b/a and
      T-786C polymorphisms of eNOS gene do not have any association with preeclampsia,
      but we found that the risk of preeclampsia was twofold in Afghan women in
      contrast to Persian and Balooch women. In a backward stepwise multiple regression
      analysis, the Afghan race and the history of preeclampsia were the risk factors
      for preeclampsia. CONCLUSION: We conclude that the presence of 4b/a and T-786C
      polymorphisms were not risk factors for preeclampsia.

PMID- 21713427
TI  - Correlation between maternal hepatitis B surface antigen carrier status with
      social, medical and family factors in an endemic area: have we overlooked
      something?
AB  - PURPOSE: Hepatitis B virus (HBV) infection is endemic in many countries, but the
      risk factors for HBV carriage in the obstetric population are unclear. METHODS: A
      survey on 1,580 women attending the antenatal clinic in an endemic region was
      conducted in order to examine the prevalence of and factors associated with
      maternal HBV carriage, including socio-demographic, medical, and previous
      obstetrical and family history, by means of a questionnaire. RESULTS: The
      prevalence of maternal HBV carriage was 9.1%, and 4.8% of women with a history of
      hepatitis B vaccination were found to be HBV carriers. Factors associated with
      maternal HBV carriage were residency status (adjusted odds ratio [aOR] 3.65 for
      immigrants; aOR 7.62 for non-residents), positive family history (aOR 3.72 for
      infected mother; aOR 5.36 for other family members), no previous vaccination (aOR
      4.39) and having previous HBsAg testing (aOR 2.26). CONCLUSIONS: The findings
      suggest that there was probably an overlooked role of horizontal transmission
      within the family setting in addition to perinatal transmission in determining
      the likelihood of HBV infection in our obstetric population. Reconfirmation of
      hepatitis B status might be necessary among individuals with a history of
      vaccination to ensure the effectiveness of their immunoprotection.

PMID- 21713428
TI  - Risk of liver-associated morbidity and mortality in a cohort of HIV and HBV
      coinfected Han Chinese.
AB  - OBJECTIVES: To investigate the incidence and risk factors of liver-associated
      morbidity and mortality in Han Chinese patients with human immunodeficiency virus
      (HIV) and hepatitis B virus (HBV) coinfection. METHODS: A retrospective study was
      conducted. RESULTS: Of the 255 subjects with HIV and HBV coinfection, 181 (71.0%)
      received lamivudine-based combined antiretroviral therapy (cART). Of the
      patients, 49/255 (19.2%) developed advanced liver diseases (ALDs) (during 5.2
      years): 30 patients developed clinically overt cirrhosis, 10 developed
      hepatocellular carcinoma and 9 developed severe reactivation of a preexisting
      chronic hepatitis B. Baseline CD4(+) cell count <200 cell/mm(3) (P = 0.013, OR =
      6.503), baseline alanine aminotransferase (ALT) elevation (P = 0.011, OR =
      14.456), and longer cumulated time with detectable HIV RNA (P = 0.008, OR =
      1.814) and HBV DNA (P = 0.014, OR = 1.536) were risk factors for ALDs
      development, while CD4(+) cell count changes >=150 cells/mm(3) within 3 months (P
      = 0.039, OR = 0.049) and the use of lamivudine-based cART (P = 0.030, OR = 0.034)
      were protective against ALDs development. CONCLUSIONS: ALDs was common among HIV
      and HBV coinfected Han Chinese patients. Lamivudine-based cART was beneficial in
      terms of sustained HBV viral suppression and resulted in less incidence of ALDs.

PMID- 21713429
TI  - Coxiella burnetii causing haemophagocytic syndrome: a rare complication of an
      unusual pathogen.
AB  - We describe an unusual presentation of Q fever with associated haemophagocytic
      syndrome, confirmed by bone marrow aspirate, Q fever polymerase chain reaction
      (PCR) and serological testing. Clinical recovery was observed after the
      commencement of doxycycline with normalisation of the patient's full blood count
      and serum biochemistry. Serial monitoring of the Q fever serology revealed the
      subsequent development of sustained high phase 1 IgG antibodies, suggestive of
      chronic Q fever. Although many infectious aetiologies have been associated with
      haemophagocytosis, Q fever has only rarely been described in this context. The
      diagnosis of Q fever is often overlooked, especially when the presentation is
      atypical. We describe how the use of PCR testing significantly shortened the
      interval to definitive diagnosis and helped elucidate the underlying cause of the
      patient's haematological disorder.

PMID- 21713430
TI  - Deep sternal wound infection due to Pasteurella multocida: the first case report
      and review of literature.
AB  - Pasteurella multocida is a Gram-negative bacterium recovered from a wide variety
      of wild and domestic animals and has mostly been associated with infection
      following animal bites. We present the first reported case of a patient who
      developed a postoperative sternal wound infection due to P. multocida complicated
      by bloodstream infection. The outcome was favorable following surgical
      debridement and antimicrobial therapy. We also review the literature regarding P.
      multocida postoperative wound infections.

PMID- 21713431
TI  - Legionellosis must be kept in mind in case of pneumonia with lung abscesses in
      children receiving therapeutic steroids.
AB  - A 10-year-old boy, who had received recurrent short-course treatments with
      steroids to control severe autoimmune thrombocytopaenia, developed Legionnaires'
      disease as community-acquired pneumonia. Legionella pneumophila pneumonia was
      complicated by an extended abscess of the right inferior lobe, leading to
      residual lung cavities. Legionellosis must be kept in mind as the differential
      diagnosis in the case of severe pneumonia and with lung abscesses in children
      receiving therapeutic steroids. Legionella-specific diagnostic tests (polymerase
      chain reaction [PCR] in respiratory samples or urine antigen assay) and, also,
      specific empirical antibiotic combination therapy are required for the early
      detection and treatment of L. pneumophila pneumonia in childhood.

PMID- 21713432
TI  - The road ahead: less travelled and more arduous than initially envisioned.

PMID- 21713433
TI  - Adding fuel to the fire: alcohol's effect on the HIV epidemic in Sub-Saharan
      Africa.
AB  - Alcohol consumption adds fuel to the HIV epidemic in sub-Saharan Africa (SSA).
      SSA has the highest prevalence of HIV infection and heavy episodic drinking in
      the world. Alcohol consumption is associated with behaviors such as unprotected
      sex and poor medication adherence, and biological factors such as increased
      susceptibility to infection, comorbid conditions, and infectiousness, which may
      synergistically increase HIV acquisition and onward transmission. Few
      interventions to decrease alcohol consumption and alcohol-related sexual risk
      behaviors have been developed or implemented in SSA, and few HIV or health
      policies or services in SSA address alcohol consumption. Structural
      interventions, such as regulating the availability, price, and advertising of
      alcohol, are challenging to implement due to the preponderance of homemade
      alcohol and beverage industry resistance. This article reviews the current
      knowledge on how alcohol impacts the HIV epidemic in SSA, summarizes current
      interventions and policies, and identifies areas for increased research and
      development.

PMID- 21713434
TI  - Impacts of organic and inorganic fertilizers on nitrification in a cold climate
      soil are linked to the bacterial ammonia oxidizer community.
AB  - The microbiology underpinning soil nitrogen cycling in northeast China remains
      poorly understood. These agricultural systems are typified by widely contrasting
      temperature, ranging from -40 to 38 degrees C. In a long-term site in this
      region, the impacts of mineral and organic fertilizer amendments on potential
      nitrification rate (PNR) were determined. PNR was found to be suppressed by long
      term mineral fertilizer treatment but enhanced by manure treatment. The abundance
      and structure of ammonia-oxidizing bacterial (AOB) and archaeal (AOA) communities
      were assessed using quantitative polymerase chain reaction and denaturing
      gradient gel electrophoresis techniques. The abundance of AOA was reduced by all
      fertilizer treatments, while the opposite response was measured for AOB, leading
      to a six- to 60-fold reduction in AOA/AOB ratio. The community structure of AOA
      exhibited little variation across fertilization treatments, whereas the structure
      of the AOB community was highly responsive. PNR was correlated with community
      structure of AOB rather than that of AOA. Variation in the community structure of
      AOB was linked to soil pH, total carbon, and nitrogen contents induced by
      different long-term fertilization regimes. The results suggest that manure
      amendment establishes conditions which select for an AOB community type which
      recovers mineral fertilizer-suppressed soil nitrification.

PMID- 21713435
TI  - Environmental conditions constrain the distribution and diversity of archaeal
      merA in Yellowstone National Park, Wyoming, U.S.A.
AB  - The distribution and phylogeny of extant protein-encoding genes recovered from
      geochemically diverse environments can provide insight into the physical and
      chemical parameters that led to the origin and which constrained the evolution of
      a functional process. Mercuric reductase (MerA) plays an integral role in mercury
      (Hg) biogeochemistry by catalyzing the transformation of Hg(II) to Hg(0).
      Putative merA sequences were amplified from DNA extracts of microbial communities
      associated with mats and sulfur precipitates from physicochemically diverse Hg
      containing springs in Yellowstone National Park, Wyoming, using four PCR primer
      sets that were designed to capture the known diversity of merA. The recovery of
      novel and deeply rooted MerA lineages from these habitats supports previous
      evidence that indicates merA originated in a thermophilic environment.
      Generalized linear models indicate that the distribution of putative archaeal
      merA lineages was constrained by a combination of pH, dissolved organic carbon,
      dissolved total mercury and sulfide. The models failed to identify statistically
      well supported trends for the distribution of putative bacterial merA lineages as
      a function of these or other measured environmental variables, suggesting that
      these lineages were either influenced by environmental parameters not considered
      in the present study, or the bacterial primer sets were designed to target too
      broad of a class of genes which may have responded differently to environmental
      stimuli. The widespread occurrence of merA in the geothermal environments implies
      a prominent role for Hg detoxification in these environments. Moreover, the
      differences in the distribution of the merA genes amplified with the four merA
      primer sets suggests that the organisms putatively engaged in this activity have
      evolved to occupy different ecological niches within the geothermal gradient.

PMID- 21713436
TI  - Density of Gr1-positive myeloid precursor cells, p-STAT3 expression and gene
      expression pattern in canine mammary cancer metastasis.
AB  - The very recent studies on human and mice models have indicated an important role
      of myeloid precursor cells (progenitors or not fully differentiated cells that
      express the Gr1 antigen also called Gr1-positive myeloid suppressor cells) in the
      tumor progression and metastasis. They are thought to suppress the immune system
      and promote angiogenesis via Signal transducer and activator of transcription 3
      (STAT3) activation. As of now there is no data available on the correlation of
      Gr1-positive cell number, phosphorylated STAT3 (p-STAT3) expression and cancer
      ability to metastasis. Thus, we counted the myeloid precursor cell number and
      analyzed p-STAT3 expression in 50 canine mammary tumors that gave local/distant
      metastases and did not metastasize. We showed that the number of Gr1-positive
      cells and p-STAT3 expression are significantly higher (p < 0.001) in the
      metastatic tumors than in the non-metastatic ones. We also observed higher
      expression of p-STAT3 in the canine mammary cancer cell lines with metastatic
      potential than in other cell lines (p < 0.001). Moreover, the number of myeloid
      precursors and p-STAT3 expression in metastatic tumors correlate strongly. The
      tumor infiltrating myeloid precursor cells may invigorate the STAT3 activity
      (probably via vascular endothelial growth factor - VEGF) that contributes to the
      tumor angiogenesis and furthermore tumor's ability to metastasize. The analysis
      of gene expression in canine mammary cancer cell lines with metastatic potential
      indicated that semaphorin 3B (SEMA3B) and neuropilin receptors (NRP) may also be
      important elements in this process. Thus, we discuss the possible interactions
      within the tumor that may be required for cancer metastatis.

PMID- 21713437
TI  - Identification of a new genotype of canine distemper virus circulating in
      America.
AB  - Canine Distemper is a highly contagious viral systemic disease that affects a
      wide variety of terrestrial carnivores. Canine Distemper virus (CDV) appears
      genetically heterogeneous, markedly in the hemagglutinin protein (H), showing
      geographic patterns of diversification that are useful to monitor CDV molecular
      epidemiology. In Mexico the activity of canine distemper remains high in dogs,
      likely because vaccine prophylaxis coverage in canine population is under the
      levels required to control effectively the disease. By phylogenetic analysis
      based on the nucleoprotein (N) and on the H genes, Mexican CDV strains collected
      between 2007 and 2010 were distinguished into several genovariants, all which
      constituted a unique group, clearly distinct from field and vaccine strains
      circulating worldwide, but resembling a CDV strain, 19876, identified in
      Missouri, USA, 2004, that was genetically unrelated to other North-American CDV
      strains. Gathering information on the genetic heterogeneity of CDV on a global
      scale appears pivotal in order to investigate the origin and modalities of
      introduction of unusual/novel CDV strains, as well as to understand if vaccine
      breakthroughs or disease epidemics may be somewhat related to genetic/antigenic
      or biological differences between field and vaccine strains.

PMID- 21713438
TI  - Successful treatment of a newborn with genetically confirmed long QT syndrome 3
      and repetitive Torsades De Pointes tachycardia.

PMID- 21713439
TI  - Outcomes and risk factors for mortality in premature neonates with critical
      congenital heart disease.
AB  - We sought to describe contemporary outcomes and identify risk factors for
      hospital mortality in premature neonates with critical congenital heart disease
      who were referred for early intervention. Neonates who were born before 37 weeks'
      gestation with critical congenital heart disease and admitted to our institution
      from 2002 to 2008 were included in this retrospective cohort study. Critical
      congenital heart disease was defined as a defect requiring surgical or
      transcatheter cardiac intervention or a defect resulting in death within the
      first 28 days of life. Logistic regression analyses were performed to identify
      risk factors for mortality before hospital discharge. The study included 180
      premature neonates, of whom 37 (21%) died during their initial hospitalization,
      including 6 (4%) before cardiac intervention and 31 (17%) after cardiac
      intervention. For the 174 patients undergoing cardiac intervention, independent
      risk factors for mortality were a 5 min Apgar score <= 7, need for
      preintervention mechanical ventilation, and Risk Adjustment in Congenital Heart
      Surgery category >= 4 or not assignable. Mortality for premature infants with
      critical congenital heart disease who are referred for early intervention remains
      high. Patients with lower Apgar scores who receive preintervention mechanical
      ventilation and undergo more complex procedures are at greatest risk.

PMID- 21713440
TI  - Renal safety in pediatric imaging: randomized, double-blind phase IV clinical
      trial of iobitridol 300 versus iodixanol 270 in multidetector CT.
AB  - BACKGROUND: It is debated whether iso-osmolar and low-osmolar contrast media are
      associated with different incidences of contrast medium-induced nephropathy (CIN)
      in patients with renal insufficiency. OBJECTIVE: To compare the incidence of CIN
      in children undergoing contrast-enhanced multidetector computer tomography (MDCT)
      with intravenous injection of low-osmolar (iobitridol, Xenetix(r) 300) or an iso
      osmolar (iodixanol, Visipaque(r) 270) iodinated contrast medium. MATERIALS AND
      METHODS: One hundred forty-six children with normal renal function were included
      in this multicenter trial and underwent contrast-enhanced MDCT. The primary
      endpoint was the relative change in creatinine clearance from 48 h pre- to 72 h
      postcontrast medium administration using a noninferiority analysis in the intent
      to-treat (ITT, n = 128) and per protocol (n = 68) populations. Secondary
      endpoints were incidence of CIN, global image quality, diagnostic efficacy and
      clinical safety. RESULTS: In the ITT population, the noninferiority of iobitridol
      over iodixanol was demonstrated. CIN incidence was 4.8% (three cases) with
      iobitridol and 10.6% (seven cases) with iodixanol (not significant). No
      statistically significant differences were observed for the secondary endpoints.
      CONCLUSION: Comparable satisfactory safety profiles were confirmed for both
      contrast media, with no significant difference in the incidence of CIN in
      children with normal renal function.

PMID- 21713441
TI  - A case of Sjogren-Larsson syndrome with minimal MR imaging findings facilitated
      by proton spectroscopy.
AB  - We present a 5-year-old girl who was ultimately diagnosed with Sjogren-Larsson
      syndrome (SLS). Although her MRI findings were minimal compared to previously
      published cases, prominent and characteristic abnormal lipid peaks on single
      voxel proton MR spectroscopy ((1)H-MRS) facilitated the diagnosis. This case
      emphasizes the importance and usefulness of (1)H-MRS in diagnosing SLS.

PMID- 21713442
TI  - Abdominal cocoon: a unique presentation in an immunodeficient infant.
AB  - Abdominal cocoon is a rare disorder that may pose a diagnostic conundrum in
      patients presenting with intermittent symptoms of small bowel obstruction. We
      describe the imaging findings of a unique case of abdominal cocoon that presented
      in infancy.

PMID- 21713443
TI  - Are there control processes, and (if so) can they be studied?
AB  - Generally, so-called control processes are thought to be necessary when we must
      perform one out of several competing actions. Some examples include performance
      of a less well-practiced action instead of a well-practiced one (prepotency);
      learning a new action (novelty); and rapidly switching from one action to another
      (task-switching). While it certainly is difficult to perform the desired action
      in these circumstances, it is less clear that a separate set of processes (e.g.,
      control processes) are necessary to explain the observed behavior. Another way to
      approach the study of control processes is to investigate physiological dependent
      measures (e.g., electrophysiological or neuroimaging measures). Although these
      offer another avenue of inquiry into control processes, they have yet to furnish
      unambiguous evidence that control processes exist. While this might suggest that
      there are no control processes, it is also possible that our methods are
      insufficiently sensitive to measure control processes. We have investigated this
      latter possibility using tasks that are neuroanatomically distinct, though within
      the same modality (vision). This approach did not yield evidence for a separable
      set of control processes. However, recent works using a task-switching paradigm
      in which subjects switch between a visual and an auditory task suggest that
      switching both task and modality may be importantly different than switching task
      within a given modality. This may represent a way forward in the study of control
      processes.

PMID- 21713444
TI  - Genome sequence analyses of two isolates from the recent Escherichia coli
      outbreak in Germany reveal the emergence of a new pathotype: Entero-Aggregative
      Haemorrhagic Escherichia coli (EAHEC).
AB  - The genome sequences of two Escherichia coli O104:H4 strains derived from two
      different patients of the 2011 German E. coli outbreak were determined. The two
      analyzed strains were designated E. coli GOS1 and GOS2 (German outbreak strain).
      Both isolates comprise one chromosome of approximately 5.31 Mbp and two putative
      plasmids. Comparisons of the 5,217 (GOS1) and 5,224 (GOS2) predicted protein
      encoding genes with various E. coli strains, and a multilocus sequence typing
      analysis revealed that the isolates were most similar to the entero-aggregative
      E. coli (EAEC) strain 55989. In addition, one of the putative plasmids of the
      outbreak strain is similar to pAA-type plasmids of EAEC strains, which contain
      aggregative adhesion fimbrial operons. The second putative plasmid harbors genes
      for extended-spectrum beta-lactamases. This type of plasmid is widely distributed
      in pathogenic E. coli strains. A significant difference of the E. coli GOS1 and
      GOS2 genomes to those of EAEC strains is the presence of a prophage encoding the
      Shiga toxin, which is characteristic for enterohemorrhagic E. coli (EHEC)
      strains. The unique combination of genomic features of the German outbreak
      strain, containing characteristics from pathotypes EAEC and EHEC, suggested that
      it represents a new pathotype Entero-Aggregative-Haemorrhagic E scherichia c oli
      (EAHEC).

PMID- 21713445
TI  - Clinico-pathological correlations in neurodegeneration.

PMID- 21713446
TI  - Triptolide augments the effects of 5-lipoxygenase RNA interference in suppressing
      pancreatic tumor growth in a xenograft mouse model.
AB  - PURPOSE: Pancreatic cancer has one of the highest fatality rates of all cancers,
      and new strategies or reagents to tackle this disease are needed. Triptolide (TL)
      is able to potently inhibit the growth of pancreatic tumor cells in vitro. On the
      other hand, blockage of 5-LOX pathway might be useful for treatment of pancreatic
      cancer. In the current study, we tested the effects of 5-LOX RNA interference and
      TL individually or in combination in suppressing human pancreatic tumor growth in
      xenograft mouse model. METHODS: 5-LOX short hairpin RNA (shRNA) vectors were
      developed and screened out for their efficacy in human pancreatic cancer cell
      line SW1990 in vitro. Their antitumor effects were also evaluated by measuring
      cell proliferation and apoptosis. An effective 5-LOX shRNA was given alone or in
      combination with TL to treat pancreatic tumor xenograft. Expression levels of 5
      LOX and VEGF were measured with Western blotting and immunohistology. RESULTS:
      Knocking down 5-LOX gene suppressed cancer cell growth in vitro and intra-tumoral
      delivering of 5-LOX shRNA inhibited growth of transplanted tumor in vivo. TL
      treatment induced tumor suppression and greatly enhanced antitumor effects of 5
      LOX shRNA in the mouse model. 5-LOX RNA interference or TL treatment suppresses
      VEGF expression in tumor tissue, and combined treatment further reduces its
      expression. CONCLUSIONS: Both treatments exerted antitumor effects in vivo, and
      combined use of the two approaches produced more powerful antitumor effects.
      Synergistic effects of combined treatment in VEGF expression may contribute to
      the mechanisms of the strong antitumor effects.

PMID- 21713447
TI  - The role of Tau protein in resistance to paclitaxel.
AB  - Resistance to taxanes, related to limited efficacy of systemic therapy in cancer
      patients, is multifactorial. Among mechanisms of resistance to taxanes, those
      related to microtubule-associated proteins (MAP), including protein Tau, are of
      great importance. Protein Tau (50-64 kD) binds to beta-tubulin in the same place
      as paclitaxel. In preclinical studies, low expression of Tau in cancer cells was
      associated with increased sensitivity to paclitaxel. High expression of Tau
      protein in ER-positive breast cancers indicates resistance to taxane-containing
      chemotherapy and sensitivity to hormonal treatment. This article reviews current
      knowledge on predictive value of protein Tau in response to taxanes. Better
      understanding of its role may facilitate patients selection to this sort of
      treatment and lead to treatment optimization.

PMID- 21713448
TI  - Live chilling of Atlantic salmon: physiological response to handling and
      temperature decrease on welfare.
AB  - Investigation of the physiological effects of live chilling in Atlantic salmon,
      Salmo salar, has been performed in two experiments. In the first, fish (mean
      weight 840 g) acclimatized to either 16, 8, or 4 degrees C were directly
      transferred horizontally or vertically (9 combinations) to water temperatures of
      16, 8, 4, or 0 degrees C using a dip net. Blood samples were collected at 1 and 6
      h (h) post-transfer. In the second experiment, fish (mean weight 916 g)
      acclimatized to 16 degrees C were exposed to four temperature-drop regimes (no
      physical handling): 16-4 degrees C (over 5 h), 16-4 degrees C (over 1 h), 16-0
      degrees C (over 5 h), and 16-0 degrees C (over 1 h). Blood samples were collected
      1 h post-temperature drop. Physical transfers in the first trial, i.e.,
      temperature drops, resulted in immediate (1 h) increases in blood lactate
      concentrations at all three temperatures, but levels were significantly reduced
      and close to pre-transfer levels after 6 h. Horizontal transfers, i.e., 16-16
      degrees C, 8-8 degrees C, and 4-4 degrees C, resulted in similar increases and
      were not significantly different from the groups exposed to temperature drops.
      The most severe vertical transfer (16-0) resulted in a swift loss of equilibrium
      and eventually death. In experiment 2, temperature drops from 16 to 4 degrees C
      and from 16 to 0 degrees C over a period of one or 5 h, without physically
      handling the fish, resulted in no significant increases in any of the measured
      parameters 1 h post-transfer, except in the 16-0 (1 h) group. The latter
      experienced a significant increase in blood sodium, glucose, lactate, and
      cortisol levels compared to all other groups. The results suggest that salmon are
      capable of tolerating relatively steep temperature drops without any significant
      negative effects on blood stress parameters and that physical stress from
      handling overrides the effect of thermal insults.

PMID- 21713449
TI  - Reconstitution and functional analyses of neutrophils and distinct subsets of
      monocytes after allogeneic stem cell transplantation.
AB  - PURPOSE: The aim of the study was to investigate the recovery of the innate
      immune system within the first 100 days after allogeneic peripheral blood stem
      cell transplantation (PBSCT) and to elucidate a potential correlation with such
      important events as severe infectious complications or graft-versus-host disease
      (GvHD). METHODS: In 30 consecutive patients who underwent allogeneic PBSCT,
      absolute numbers of neutrophils and monocytes were determined and different
      functional analyses performed at different time points (day +30, +60 and +90,
      respectively). The capacity to phagocyte Escherichia coli (E. coli) as well as
      the induction of oxidative burst after incubation with different stimuli (Phorbol
      12-myristate-13-acetate; PMA, the chemotactic peptide N-formyl-Met-Leu-Phe; f-MLP
      or opsonized E. coli) were analysed after engraftment. RESULTS: There was a rapid
      reconstitution concerning the capability of both neutrophils and monocytes to
      phagocyte E. coli without a significant increase between day +30 and +90. In
      contrast, a twofold increase of monocyte oxidative burst after incubation with
      PMA at day +90 was observed (P = 0.017). Furthermore, the ability of neutrophils
      to induce oxidative burst after ingestion with E. coli was impaired on day +30
      with a significant functional reconstitution on day +60 (P = 0.01). The oxidative
      burst activity following incubation with f-MLP did not show significant changes
      after stem cell engraftment. Analysis of numeric reconstitution of CD14+CD16+
      monocytes demonstrated a potential correlation with a decreased incidence of
      chronic GvHD. CONCLUSION: The functional recovery of neutrophils and monocytes in
      the early period after allogeneic PBSCT differs not only concerning phagocytosis
      and oxidative burst but also with respect to the stimulus and the cell population
      that was analysed for oxidative burst activity. The subset of CD16+CD14+
      monocytes might be a predictor for a reduced risk of chronic GvHD.

PMID- 21713450
TI  - Influence of weather variables on pain severity in end-stage osteoarthritis.
AB  - PURPOSE: Patients often attribute increasing pain in an arthritic joint to
      changing weather patterns. Studies examining the impact of weather on pain
      severity have yielded equivocal and sometimes contradictory results. The
      relationship between subchondral pseudocysts and the role they play in this
      phenomenon has not been explored. METHODS: Fifty-three patients with end-stage
      osteoarthritis of the hip completed daily pain severity visual analogue scale
      (VAS) scores over a one month period. Radiographs were reviewed to determine the
      presence of pseudocysts. Data pertaining to precipitation, atmospheric pressure
      and temperature were collected from the nearest weather station. A generalised
      linear mixed model was used to explore the relationship between weather
      variables, cysts and pain severity. RESULTS: Pain levels increased as a function
      of absolute change in atmospheric pressure from one day to the next.
      Precipitation, temperature and the presence of subchondral pseudocysts were not
      shown to influence pain severity. CONCLUSIONS: This data supports the belief held
      by many osteoarthritic patients that changing weather patterns influence their
      pain severity.

PMID- 21713451
TI  - Effect of lactoferrin on osteogenic differentiation of human adipose stem cells.
AB  - PURPOSE: Many in vitro studies of the analysis of the lactoferrin (LF) effect on
      cells have been reported. However, no study has yet investigated the effect of LF
      on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The
      aim of this study was to evaluate the effect of LF on osteogenic differentiation
      of human adipose stem cells. METHODS: The hADSCs were cultured in an osteogenic
      medium with 0, 10, 50 and 100 MUg/ml LF, respectively. hADSC proliferation was
      analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic
      differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von
      Kossa staining and real-time polymerase chain reaction (RT-PCR). RESULTS: Cell
      proliferation was significantly increased by LF in a dose-dependent manner from
      days 4 to 14. Cells cultured with 100 MUg/ml LF presented a higher activity
      compared with the control. The deposition of calcium was increased after the
      addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin
      (OCN) and RUNX2 increased markedly as a result of LF treatment. CONCLUSIONS: We
      have shown for the first time that LF could promote the proliferation and
      osteogenic differentiation of hADSCs, which could be a promising approach for
      enhancing osteogenic capacity of cell-based construction in bone tissue
      engineering.

PMID- 21713452
TI  - Acute mastoiditis in children: 10 years experience in a French tertiary
      university referral center.
AB  - Acute mastoiditis have been increasingly reported in the last decade, with
      bacteriologic modifications and new therapeutic guidelines. This study is a
      retrospective review of 36 children hospitalized for acute mastoiditis in a
      French tertiary university referral center from 1999 to 2009, to assess
      incidence, bacteriology of pathogens and management. There were 10 periosteitis
      and 26 subperiosteal abscesses. There was a trend toward increased incidence over
      the past 10 years. The mean age of the patients was 31.8 months. A total of 63.2%
      children received 7.2 days antibiotic prior to hospitalization for acute otitis
      media, with sensitive pathogens in 80%. The pathogens were Streptococcus
      pneumoniae (36.1%), S. pyogenes A (13.9%), Staphylococcus coagulase-negative
      (13.9%), Pseudomonas aeruginosa (8.3%), Fusobacterium necroforum (8.3%) and
      Haemophiluss influenzae (2.8%). Cultures were negative in 16.7%. All patients
      received intravenous antibiotics. Eleven patients underwent bilateral myringotomy
      with or without tympanostomy tubes. Mastoidectomy was performed in 24 patients.
      Decrease in the length of hospitalization and delay from admission to surgery
      were significantly correlated. We observed a trend in the increase of acute
      mastoiditis at our center. The pathogens were dominated by S. pneumoniae. F.
      necroforum and P. aerguginosae were pathogens found in children over 2 years of
      age. Mastoidectomy was performed in 92.3% of subperiostal abscesses. However,
      there has been a trend toward conservative nonsurgical treatment in recent
      reported studies and further prospective studies are warranted to evaluate the
      long-term sequelae.

PMID- 21713453
TI  - The value of 18F-FDG-PET/CT imaging for sinonasal malignant melanoma.
AB  - The aim this study was to evaluate imaging findings using position emission
      tomography (PET) in combination with computed tomography (CT) and 18F
      fluorodeoxyglucose ((18)F-FDG) in sinonasal malignant melanoma (SNMM) of the head
      and neck in a retrospective analysis of a consecutive cohort of patients. (18)F
      FDG-PET/CT examinations were performed for initial staging and compared with CT
      or magnetic resonance tomography (MRI), and (18)F-FDG-PET alone. Medical records
      were reviewed retrospectively with regard to the location and the size of the
      tumor. Furthermore, locoregional and distant metastases with a consecutive change
      in therapy detected by (18)F-FDG-PET/CT were assessed. Ten patients suffering
      from sinonasal malignant melanoma were staged and followed by (18)F-FDG-PET/CT
      imaging. A total of 34 examinations were obtained. (18)F-FDG-PET/CT depicted all
      primary tumors adequately. Aside from one cerebral metastasis all regional and
      distant metastases were truly identified by using this method. In summary, if
      available, (18)F-FDG-PET/CT is a valuable imaging modality for staging and re
      staging sinonasal malignant melanoma to evaluate expansion of the primary tumor,
      locoregional disease, and distant metastases.

PMID- 21713454
TI  - Surgical classification of different types of en bloc resection for primary
      malignant sacral tumors.
AB  - PURPOSE: The purpose of the study was to develop a surgical classification system
      for primary malignant sacral tumors. METHODS: The sacrum is divided into three
      regions 1, 2 and 3 by the S1-S2 and S2-S3 junctions. En bloc resections were
      classified into five types: type I involves regions 1, or 1 and 2, or regions 1,
      2 and 3, type II involves regions 2 and 3, and type III involves only region 3.
      Type IV includes sagittal hemisacrectomy and resection of a portion of the
      adjacent ilium. Type V includes the sacrum and the fifth lumbar vertebra. 117
      patient cases (68 females and 49 males) were reviewed. RESULTS: There were two
      perioperative deaths. Of the 35 patients who should have undergone type I
      resection, local recurrence (LR) occurred in four of the 14 patients who
      underwent type I resection with free margins without tumor rupture. The other 21
      patients underwent piecemeal resection, and LR occurred in 15 (P = 0.013). 35
      patients underwent type II resection. Free margin without tumor rupture was
      accomplished in 26 and LR occurred in 6. Tumor rupture (TR) occurred in the other
      9 and LR occurred in seven (Yates' P = 0.012). All 33 patients underwent type III
      resection with free margins without tumor rupture. LR occurred in five. 11
      patients had type IV resection. Free margin without tumor rupture was
      accomplished in seven and LR occurred in three. TR occurred in the other four,
      and LR occurred in two (Yates' P = 0.689). One patient underwent type V resection
      with free margin without tumor rupture and LR occurred. Postoperatively, less
      than 1/3 needed long-term urethral catheterization. No patients received
      colostomy for postoperative fecal incontinence. All the patients were able to
      ambulate. CONCLUSION: Our classification system and the corresponding surgical
      approaches are helpful in dealing with primary malignant sacral tumors. Better
      oncologic results could be expected if free margin without tumor rupture was
      accomplished.

PMID- 21713455
TI  - Postpartum depression: the distribution of severity in a community sample.

PMID- 21713456
TI  - The neural processing of negative emotion postpartum: a preliminary study of
      amygdala function in postpartum depression.
AB  - While contemporary diagnostic nosology characterizes postpartum depression (PPD)
      as a specifier of a major depressive disorder (MDD), this classification
      continues to be questioned. Functional magnetic resonance imaging (fMRI) holds
      the promise of helping to characterize the neuroanatomical dysfunction associated
      with dysregulated emotion after childbirth. Twenty postpartum women underwent
      fMRI in the presence of emotionally valenced stimuli. The observation of relative
      amygdala non-responsivity in subjects demonstrating greater depression
      symptomotology stands in contrast to imaging studies of MDD and provides insight
      into possible phenotypic differences of PPD.

PMID- 21713457
TI  - What accounts for depressive symptoms among mothers?: the impact of socioeconomic
      status, family structure and psychosocial stress.
AB  - OBJECTIVES: Based on a cross-sectional population survey of 3,129 women with
      minor children, it was analyzed how socioeconomic status, family structure and
      perceived psychosocial stress are linked and how they contributed to women's self
      reported depressive symptoms. METHODS: Pearson's chi(2) test and multi-factor
      analysis of variance were used for investigating relationships between social
      status, family characteristics and psychosocial stress. Logistic regression
      models were computed for estimating their impact on depressive symptoms. RESULTS:
      Mothers having more than two children, early mothers and single mothers were
      prone to socioeconomic disadvantages. Low income was associated with higher
      psychosocial stress, however also an inverse social gradient was found indicating
      increased psychosocial stress among higher educated mothers. Having a youngest
      child below 16 years and low income increased while being a housewife was
      associated with decreased risks of depressive symptoms. Psychosocial stress, in
      particular due to family demands, conflicts with (former) partner and loneliness
      revealed to be highly relevant for depressive symptoms. CONCLUSIONS: The findings
      are pointing to the importance of life-phase specific stressors for explaining
      depressive symptoms among mothers.

PMID- 21713458
TI  - Remembrances of Corwin Hansch.

PMID- 21713459
TI  - Cytomorphological changes in buccal mucosa of patients treated with low-level
      1,064-nm laser radiation.
AB  - The aim of this study was to examine the cytomorphological changes occurring in
      the buccal mucosa in patients treated with low-level 1,064-nm laser radiation.
      Seventeen individuals (12 males, five females) 18-24 years of age were included
      in the study. Low-level 1,064-nm laser radiation was applied to the right buccal
      mucosa near the premolar region; this therapy was repeated for 10 days. Buccal
      epithelial cells were collected from the right and left premolar regions of the
      individuals with a brush before and after therapy. The specimens collected from
      the left side were measured cytomorphometrically and used for the control group.
      Student's t test was used for statistical comparison of the values of the buccal
      epithelial cells collected from individuals; a p value < 0.05 was considered
      statistically significant. None of the patients showed any adverse reactions to
      the low-level 1,064-nm laser radiation therapy during application. There was no
      cytogenetic damage to the therapied or non-therapied regions in the buccal mucosa
      cells, as determined cytomorphologically. The results suggest that low-level
      1,064-nm laser radiation therapy has no genotoxic potential. Within the
      limitations of this study, it can be concluded that low-level 1,064-nm laser
      radiation therapy may be used safely in dental treatments.

PMID- 21713460
TI  - Preclinical evaluation of drug in adhesive type ondansetron loaded transdermal
      therapeutic systems.
AB  - The in vivo assessment of percutaneous absorption of molecules is a very
      important step in the evaluation of any transdermal drug delivery system and a
      key goal in the design and optimization of transdermal dosage forms lies in
      understanding the factors that determine a good in vivo performance. The
      objective of the present investigation is to assess the in vivo performance of an
      optimized transdermal system of ondansetron hydrochloride in rabbits and to
      generate preclinical pharmacokinetic data. The pharmacokinetic performance of
      ondansetron hydrochloride following intravenous and transdermal administration
      was studied in rabbits following non compartmental pharmacokinetic analysis. The
      pharmacokinetic parameters such as area under the curve, elimination rate
      constant, elimination half life and mean residence time, were significantly (P <
      0.01) different following transdermal administration compared to intravenous
      administration. Absolute bioavailability of the transdermal film studied was
      estimated to be 0.37 +/- 0.06 which is quite low because a very high drug loading
      in the transdermal system was essential to achieve sufficient thermodynamic
      activity for transdermal permeation. Though in vivo studies in rabbits are found
      promising, investigations in healthy human subjects are essential to confirm the
      performance of the developed transdermal films.

PMID- 21713461
TI  - Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in
      human liver microsomes.
AB  - Wogonin, derived from the root of Scutellaria baicalensis, is a popular herb for
      its anticancer, anti-inflammatory, neuroprotective and anti-convulsant effects.
      The purpose of this study was to investigate the effect of wogonin on human
      hepatic cytochrome P450s (CYP450s) in vitro. Isoform-specific substrate probes of
      CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 were incubated in human liver microsomes with
      or without wogonin. IC(50) and K (i) values were estimated and the types of
      inhibition were determined. Wogonin was a potent, competitive inhibitor of CYP1A2
      (K (i) = 0.24 MUM), and a weak inhibitor of CYP2C19 (IC(50) = 101.10 MUM), but
      was not able to inhibit CYP2C9, CYP2D6, CYP2E1 and CYP3A4 (IC(50) > 200 MUM).
      Wogonin could inhibit the activity of CYP1A2 and CYP2C19 with varying potency,
      while it is a strong inhibitor of CYP1A2. These findings suggested that it was
      necessary to study the potential pharmacokinetic drug interaction in vivo.

PMID- 21713462
TI  - Comparing removal of trace organic compounds and assimilable organic carbon (AOC)
      at advanced and traditional water treatment plants.
AB  - Stability of drinking water can be indicated by the assimilable organic carbon
      (AOC). This AOC value represents the regrowth capacity of microorganisms and has
      large impacts on the quality of drinking water in a distribution system. With
      respect to the effectiveness of traditional and advanced processing methods in
      removing trace organic compounds (including TOC, DOC, UV(254), and AOC) from
      water, experimental results indicate that the removal rate of AOC at the Cheng
      Ching Lake water treatment plant (which utilizes advanced water treatment
      processes, and is hereinafter referred to as CCLWTP) is 54%, while the removal
      rate of AOC at the Gong Yuan water treatment plant (which uses traditional water
      treatment processes, and is hereinafter referred to as GYWTP) is 36%. In advanced
      water treatment units, new coagulation-sedimentation processes, rapid filters,
      and biological activated carbon filters can effectively remove AOC, total organic
      carbon (TOC), and dissolved organic carbon (DOC). In traditional water treatment
      units, coagulation-sedimentation processes are most effective in removing AOC.
      Simulation results and calculations made using the AutoNet method indicate that
      TOC, TDS, NH(3)-N, and NO(3)-N should be regularly monitored in the CCLWTP, and
      that TOC, temperature, and NH(3)-N should be regularly monitored in the GYWTP.

PMID- 21713463
TI  - Determination of ametryn in sugarcane and ametryn-atrazine herbicide formulations
      using spectrophotometric method.
AB  - A sensitive spectrophotometric method has been developed for determination of
      ametryn in agricultural samples. The proposed method was based on reaction with
      pyridine and further coupling with sulfanilic acid to form a colored product. The
      absorbance was measured at 400 nm with a molar absorptivity of 2.1 x 10(5) L mol(
      1) cm(-1). The method shows a linear range from 0.2-20 MUg mL(-1) with limit of
      detection and limit of quantification 0.16 and 0.54 MUg mL(-1), respectively. The
      method has been successfully applied to the determination of ametryn in sugarcane
      juice and commercial formulations after separation of ametryn from triazine
      herbicides based on solvent extraction. Recovery values were found to be in the
      range of 96.0 +/- 0.2% to 98.4  +/-  0.1%.

PMID- 21713464
TI  - Evaluation of trace element contents of some herbal plants and spices retailed in
      Kayseri, Turkey.
AB  - The trace element contents of seven kinds of herbal plants and spice samples
      retailed in local markets in Kayseri-Turkey were determined by flame atomic
      absorption spectrometry after digestion with HNO(3)/H(2)O(2) mixture. The
      concentration ranges for the studied elements were found as 6.0-15.2, 0-32.2,
      80.0-324.8, 8.1-386.3, and 13.1-36.2 MUg/g for copper, nickel, iron, manganese,
      and zinc, respectively. The levels of cobalt, lead, and chromium ions in all the
      investigated samples were found to be below the detection limit of flame atomic
      absorption spectrometry. The results found in the present work were compared with
      values in the literature.

PMID- 21713465
TI  - Examination of reactive phosphate fluxes in an eutrophicated coastal area.
AB  - Reactive phosphate (RP) fluxes over sediment in an eutrophic bay were obtained
      under different conditions. The results were assessed together with water column,
      sediment solid, and liquid-phase parameters. The RP fluxes ranged from 0 to 1,300
      MUgatP * m(-2)d(-1) day depending on the sediment site and other variables. At
      stations with relatively high net RP fluxes, the clay fraction was >3% and
      disproportionate with salinity, which explained why the RP effluxes decreased by
      inhibition of the organic coating on particulate matter with increased SO(4) (-2)
      ions and good competition of RP anions with SO(4) (-2). The RP flux in Fe/RP
      ratios >2 in surface water decreased to approach a minimum asymptotically, which
      was thus defined with a hyperbolic curve to determine the maximum rate of the RP
      flux (J(RP)). The [RP(porewater)](initial)/[RP(ambient)] (initial) ratios were
      suggested to govern the net RP flux regionally, so the critical value where the
      RP flux turns positive could indicate eutrophication with Chl-a values <500
      MUg/g. So, this study investigated the phosphate fluxes between sediment and
      water column and determined the factors influencing the RP fluxes in the inner
      bay of Izmir.

PMID- 21713466
TI  - Long-term variability of metals from fungicides applied in amended young vineyard
      fields of La Rioja (Spain).
AB  - The long-term variability of total Cu content from fungicides applied in a
      certified wine region of Spain (La Rioja) and of other metals (Cd, Cr, Ni, Pb,
      and Zn) was evaluated in three young vineyard soils and subsoils unamended and
      amended with spent mushroom substrates (SMS) over a 3-year period (2006-2008).
      SMS is a promising agricultural residue as an amendment to increase the soil
      organic matter content but may modify the behaviour of metals from pesticide
      utilisation in vineyards. Fresh and composted SMS was applied each year at a rate
      of 25 t ha(-1) (dry-weight). Copper concentrations in the three unamended soils
      were 21.2-88.5, 25.5-77.1, and 29.4-78.4 mg kg(-1). They exceeded natural Cu
      concentrations of the region and reference sub-lethal hazardous concentration for
      soil organism. The concentrations of Cd, Ni, Pb, and Zn were largely below the
      sub-lethal limits. Thus, although Cu levels were lower than those of established
      vineyards, vine performance, and productivity might be affected. The variation in
      behaviour between different amendments for each soil was high, so a generic
      conclusion could not be drawn. The amendment practice seemed to have caused
      temporarily Cu mobilization respect to untreated soils. Total zinc concentrations
      fall within the range of the natural soil of La Rioja and were significantly
      affected (p < 0.05) especially by fresh state SMS addition, with increasing up to
      75% respect to untreated specimen. The results indicated a build-up of fresh
      sites for metal retention at both surface and subsurface level, although no
      accumulation of metals was observed in the short-term period. However, the
      benefit for soils and the negative effects need to be monitored in the long run.

PMID- 21713467
TI  - Methyl mercury in fish--a case study on various samples collected from Ganges
      river at West Bengal.
AB  - This study investigated the presence of total mercury (Hg) and organic mercury
      levels in the muscle of 19 common fresh water fish species captured from river
      Ganges, West Bengal, India. The total mercury level found in our study may not
      cause any toxic effect, but the methyl mercury (MeHg) level in some freshwater
      fish species was surprisingly very high and toxically unacceptable. The results
      of mercury analysis in various specimens indicated that some fish muscles tended
      to accumulate high levels of Hg, and approximately 50-84% of Hg was organic
      mercury. A strong positive correlation between mercury levels in muscle with food
      habit and fish length (age) was found. Wallago attu possessed the highest amount
      of organic mercury in their muscle tissues, and it was 0.93 +/- 0.61 MUg Hg/g of
      wet weight. Whereas in small-sized fishes Eutropiichthys murius, Puntius sarana,
      Cirrhinus mrigala, Mystus vittatus or Mystus gulio, and Tilapia mossambicus, it
      was below the detection limit. Contamination in Catla catla (0.32 +/- 0.11),
      Anguilla bengalensis bengalensis (0.26 +/- 0.07 MUg Hg/g), Chitala chitala (0.25
      +/- 0.18), Rita rita (0.34 +/- 0.14), and Ompok pabda (0.26 +/- 0.04) was also
      above the 0.25 MUg Hg/g of wet weight, the limit set by the PFA for the maximum
      level for consumption of fish exposed to MeHg. Though in Labeo rohita (0.12 +/-
      0.03), Mastacembelus armatus (0.17 +/- 0.02), Pangasius pangasius (0.12 +/-
      0.16), Bagarius bagarius (0.12 +/- 0.01), and Clupisoma garua (0.1 +/- 0.01),
      concentration was below the recommended level, in Lates calcarifer (0.23 +/- 0.0)
      and Mystus aor (0.23 +/- 0.1), it was threatening. Interestingly, a low
      concentration of Hg was found in post-monsoon samples.

PMID- 21713468
TI  - Fish abundances in shoreline habitats and submerged aquatic vegetation in a tidal
      freshwater embayment of the Potomac River.
AB  - Submerged aquatic vegetation (SAV) is considered an important habitat for
      juvenile and small forage fish species, but many long-term recruitment surveys do
      not effectively monitor fish communities in SAV. To better understand the impact
      of recent large increases of SAV on the fish community in tidal freshwater
      reaches of the Potomac River, we compared traditional seine sampling from shore
      with drop ring sampling of SAV beds (primarily Hydrilla) in a shallow water
      (depths, <1.5 m) embayment, Gunston Cove. To accomplish this, we developed
      species-specific catch efficiency values for the seine gear and calculated area
      based density in both shoreline and SAV habitats in late summer of three
      different years (2007, 2008, and 2009). For the dominant species (Fundulus
      diaphanus, Lepomis macrochirus, Etheostoma olmstedi, Morone americana, Lepomis
      gibbosus, and Fundulus heteroclitus), density was nearly always higher in SAV,
      but overall, species richness was highest in shoreline habitats sampled with
      seines. Although historical monitoring of fish in Gunston Cove (and throughout
      Chesapeake Bay) is based upon seine sampling (and trawl sampling in deeper
      areas), the high densities of fish and larger areal extent of SAV indicated that
      complementary sampling of SAV habitats would produce more accurate trends in
      abundances of common species. Because drop ring samples cover much less area than
      seines and may miss rare species, a combination of methods that includes seine
      sampling is needed for biodiversity assessment. The resurgence of SAV in tidal
      freshwater signifies improving water quality, and methods we evaluated here
      support improved inferences about population trends and fish community structure
      as indicators of ecosystem condition.

PMID- 21713469
TI  - A hydrochemical and geological investigation on the Mambakkam mini watershed,
      Kancheepuram District, Tamil Nadu.
AB  - The hydrochemical characterization of groundwater is important to bring out its
      nature and usefulness. The main objective of this paper was to discuss the major
      ion chemistry of groundwater in the Mambakkam mini watershed. Besides its semi
      arid nature, rapid socioeconomic development encourages a greater demand for
      water, which leads to uncontrolled groundwater development. The groundwater of
      the study area is characterized by the dominance of alkaline earth (Ca(2+),
      Mg(2+)) and strong acids (Cl(-), SO(4)(-)) over alkalies (Na(+), K(+)) and weak
      acids (HCO(3)(-), CO(3)(-)) during both post-monsoon and pre-monsoon seasons of
      the year 2010, based on the hydrochemical facies. These have been probably
      derived from natural chemical weathering of rock minerals, ion exchange and
      anthropogenic activities of the fertilizer source. The classification based on
      the total hardness reveals that a majority of groundwater samples fall in the
      hard to very hard category during the pre-monsoon season. Based on the values of
      EC, SAR and RSC and the diagrams of USSL and Wilcox, most of the groundwater
      samples range from excellent to permissible for irrigation purposes, with a low
      alkalinity and high salinity hazard, except for a few samples in the study area.

PMID- 21713470
TI  - Hydrogeochemical processes controlling the high fluoride concentration in
      groundwater: a case study at the Boden block area, Orissa, India.
AB  - The present investigation reports the assessment of hydrochemical/geochemical
      processes controlling the concentration of fluoride in groundwater of a village
      in India (Boden block, Orissa). Boden block is one of the severely affected
      fluoride-contaminated areas in the state of Orissa (India). The sampling and
      subsequent analysis of water samples of the study area was carried out following
      standard prescribed methods. The results of the analysis indicate that 36.60%
      groundwater F(-) concentration exceeds the limit prescribed by the World Health
      Organization for drinking water. The rock interaction with groundwater containing
      high concentration of HCO(3)(-) and Na(+) at a higher pH value of the medium
      could be one of the important reasons for the release of F(-) from the aquatic
      matrix into groundwater. Geochemical classification of groundwater based on
      Chadha rectangular diagram shows that most of the groundwater samples having
      fluoride concentration more than 1.5 mg L(-1) belongs to the Na-K-HCO(3) type.
      The saturation index values evaluated for the groundwater of the study area
      indicated that it is oversaturated with respect to calcite, whereas the same is
      undersaturated with respect to fluorite content. The deficiency of calcium ion
      concentration in the groundwater from calcite precipitation favors fluorite
      dissolution leading to excess of fluoride concentration. The risk index was
      calculated as a function of fluoride level in drinking water and morbidity of
      fluorosis categorizes high risk for villages of Amera and Karlakote panchayat of
      Boden block.

PMID- 21713471
TI  - Total mercury distribution in different tissues of six species of freshwater fish
      from the Kpong hydroelectric reservoir in Ghana.
AB  - Total mercury concentrations were determined in seven tissues of 38 fish samples
      comprising six species from the Kpong hydroelectric reservoir in Ghana by cold
      vapour atomic absorption spectrometry technique using an automatic mercury
      analyzer. Mercury concentration in all the tissues ranged from 0.005 to 0.022
      MUg/g wet weight. In general, the concentration of mercury in all the tissues
      were decreasing in the order; liver > muscle > intestine > stomach > gonad > gill
      > swim bladder. Mercury concentration was generally greater in the tissues of
      high-trophic-level fish such as Clarotes laticeps, Mormyrops anguilloides and
      Chrysichthys aurutus whereas low-trophic-level fish such as Oreochromis niloticus
      recorded low mercury concentration in their tissues. The results obtained for
      total mercury concentration in the muscle tissues analysed in this study are
      below the WHO/FAO threshold limit of 0.5 MUg/g. This suggests that the exposure
      of the general public to Hg through fish consumption can be considered
      negligible.

PMID- 21713472
TI  - Determination of polychlorinated biphenyls and total mercury in two fish species
      (Esox lucius and Carassius auratus) in Anzali Wetland, Iran.
AB  - The Anzali Wetland is one of the most important ecosystems in the north of Iran,
      and parts of it were registered as a Ramsar site in 1975. However, even though,
      due to many problems, including eutrophication produced by inflow of excess
      nutrients and organic materials, the wetland was also listed on the Montreux
      Record indicating the need to take urgent remedial action. This study was
      conducted to study the levels of polychlorinated biphenyls (PCBs) and total
      mercury (THg) in two fish species (Esox lucius and Carassius auratus) as bio
      indicators of the ecosystem condition in eastern part of Anzali Wetland. The
      sampling was carried out in six different periods between years 2009 and 2010.
      The results showed that the amounts of PCBs in the muscle of northern pike were
      below the detection limit of gas chromatography, whereas the average
      concentration in goldfish was 0.449 mg/kg wet weight. Some possible reasons for
      the higher levels of PCBs in goldfish in comparison with pike have been
      discussed. No significant (p < 0.05) correlation was observed between PCBs and
      biological factors (weight, length, lipid content) for both species. On the other
      hand, the mean concentration of THg in the muscle of pike and goldfish were
      182.22 and 75.27 ng/g dry weight, respectively. Although these concentrations
      were below US-EPA criterion for human consumption (0.3 mg/kg), it pointed up a
      significant deterioration of the ecosystem condition during the past years.
      Finally, statistical analysis revealed a significant correlation between THg with
      weight and an insignificant correlation with length for pike specimens.

PMID- 21713473
TI  - Impact of socioeconomic development on ecosystem services and its conservation
      strategies: a case study of Shandong Province, China.
AB  - Ecosystems and their components provide a lot of benefits for the welfare of
      human beings. Coupled with increasing socioeconomic development, most of the
      rapidly developing and transitional countries and regions have been experiencing
      dramatic land use changes. This has resulted in a large amount of forestland,
      grassland, and wetland being occupied as residential and industrial land or
      reclaimed for arable land, which in turn results in a sharp deterioration of
      ecosystem services around the world. Shandong Province, an economically powerful
      province of China, was chosen as a case study in order to capture the impact of
      socioeconomic development on ecosystem services. By way of the study, land uses
      and their changes were categorized between 1980 and 2006, and the ecosystem
      services capital and changes of 111 counties of Shandong Province in different
      phases were evaluated, as well as the total ecosystem services capital, followed
      by the zoning of ecosystem services function region of Shandong Province. We
      found that the counties in mountainous areas and wetlands, where generally the
      prefectural-level cities are located with a rapid socioeconomic development,
      experienced a successive deterioration of ecosystem services especially during
      the 2000s. Finally, three conservation strategies for managing and improving
      ecosystem services were proposed and discussed with the aim of achieving
      coordinate and sustainable development of the socioeconomy, environment, and
      ecosystems not only in Shandong Province but also in other provinces of China, as
      well as in other developing and transitional countries and regions.

PMID- 21713474
TI  - Role of meteorology in seasonality of air pollution in megacity Delhi, India.
AB  - The winters in megacity Delhi are harsh, smoggy, foggy, and highly polluted. The
      pollution levels are approximately two to three times those monitored in the
      summer months, and the severity is felt not only in the health department but
      also in the transportation department, with regular delays at airport operations
      and series of minor and major accidents across the road corridors. The impacts
      felt across the city are both manmade (due to the fuel burning) and natural (due
      to the meteorological setting), and it is hard to distinguish their respective
      proportions. Over the last decade, the city has gained from timely interventions
      to control pollution, and yet, the pollution levels are as bad as the previous
      year, especially for the fine particulates, the most harmful of the criteria
      pollutants, with a daily 2009 average of 80 to 100 MUg/m(3). In this paper, the
      role of meteorology is studied using a Lagrangian model called Atmospheric
      Transport Modeling System in tracer mode to better understand the seasonality of
      pollution in Delhi. A clear conclusion is that irrespective of constant emissions
      over each month, the estimated tracer concentrations are invariably 40% to 80%
      higher in the winter months (November, December, and January) and 10% to 60%
      lower in the summer months (May, June, and July), when compared to annual average
      for that year. Along with monitoring and source apportionment studies, this paper
      presents a way to communicate complex physical characteristics of atmospheric
      modeling in simplistic manner and to further elaborate linkages between local
      meteorology and pollution.

PMID- 21713475
TI  - Estimating vertebrate, benthic macroinvertebrate, and diatom taxa richness in
      raftable Pacific Northwest rivers for bioassessment purposes.
AB  - The number of sites sampled must be considered when determining the effort
      necessary for adequately assessing taxa richness in an ecosystem for
      bioassessment purposes; however, there have been few studies concerning the
      number of sites necessary for bioassessment of large rivers. We evaluated the
      effect of sample size (i.e., number of sites) necessary to collect vertebrate
      (fish and aquatic amphibians), macroinvertebrate, and diatom taxa from seven
      large rivers in Oregon and Washington, USA during the summers of 2006-2008. We
      used Monte Carlo simulation to determine the number of sites needed to collect 90
      95% of the taxa 75-95% of the time from 20 randomly located sites on each river.
      The river wetted widths varied from 27.8 to 126.0 m, mean substrate size varied
      from 1 to 10 cm, and mainstem distances sampled varied from 87 to 254 km. We
      sampled vertebrates at each site (i.e., 50 times the mean wetted channel width)
      by nearshore-raft electrofishing. We sampled benthic macroinvertebrates nearshore
      through the use of a 500-MUm mesh kick net at 11 systematic stations. From each
      site composite sample, we identified a target of 500 macroinvertebrate
      individuals to the lowest possible taxon, usually genus. We sampled benthic
      diatoms nearshore at the same 11 stations from a 12-cm(2) area. At each station,
      we sucked diatoms from soft substrate into a 60-ml syringe or brushed them off a
      rock and rinsed them with river water into the same jar. We counted a minimum of
      600 valves at 1,000* magnification for each site. We collected 120-211 diatom
      taxa, 98-128 macroinvertebrate taxa, and 14-33 vertebrate species per river. To
      collect 90-95% of the taxa 75-95% of the time that were collected at 20 sites, it
      was necessary to sample 11-16 randomly distributed sites for vertebrates, 13-17
      sites for macroinvertebrates, and 16-18 sites for diatoms. We conclude that 12-16
      randomly distributed sites are needed for cost-efficient sampling of vertebrate
      richness in the main stems of our study rivers, but 20 sites markedly
      underestimates the species richness of benthic macroinvertebrates and diatoms in
      those rivers.

PMID- 21713476
TI  - Modeling wastewater discharge at the planning stage of a marine outfall system.
AB  - The possibility of marine discharge of a negatively buoyant industrial waste was
      evaluated by a modeling study using Killworth 3-D, which is the first version of
      the Modular Ocean Model (MOM). The Model was run with the recorded wind direction
      and speed on the cruise dates and the circulation patterns for surface and
      subsurface were found to be similar with the current meter measurements. Model
      scenarios have been set-up in order to estimate the intensity and direction of
      the currents in the Nemrut Bay under the condition of wind blowing from a
      definite direction for a long time. MOM model has been run for four major wind
      directions, each having duration of 10 days and the behavior of the discharge
      plume in the worst case has been traced. Also, the behavior of the discharge
      plume in the real case has been estimated by using the wind data of the region.
      According to the model results, impact of trace elements that compose the
      discharge effluent is limited both in time and space. It is concluded that trace
      elements will leave the Bay in a short time due to the short residence times.

PMID- 21713477
TI  - Development of geomorphologic instantaneous unit hydrograph for a large
      watershed.
AB  - Hill torrents cause a lot of environmental and property damage in Pakistan every
      year. Proper assessment of direct runoff in the form of hill torrents is
      essential for protection of environment, property, and human life. In this paper,
      direct surface runoff hydrograph (DSRH) was derived for a large catchment using
      the geomorphologic instantaneous unit hydrograph concept. The catchment with hill
      torrent flows in semi-arid region of Pakistan was selected for this study. It was
      divided into series of linear cascades and hydrologic parameters required for
      Nash's conceptual model, and were estimated using geomorphology of the basin.
      Geomorphologic parameters were derived from satellite images of the basin and
      ERDAS and ArcGIS were used for data processing. Computer program was developed to
      systematically estimate the dynamic velocity, its related parameters by
      optimization and thereby to simulate the DSRH. The data regarding rainfall-runoff
      and satellite images were collected from Punjab Irrigation and Power Department,
      Pakistan. Model calibration and validation was made for 15 rainfall-runoff
      events. Ten events were used for calibration and five for validation. Model
      efficiency was found to be more than 90% and root mean square error to be about
      5%. Impact of variation in model parameters (shape parameter and storage
      coefficient) on DSRH was investigated. For shape parameter, the number of linear
      cascades varied from 1 to 3 and it was found that the shaper parameter value of 3
      produced the best DSRH. Various values of storage coefficient were used and it
      was observed that the value determined from geomorphology and the dynamic
      velocity produced the best results.

PMID- 21713478
TI  - Heavy metals in the liver and muscle of Micropogonias manni fish from Budi Lake,
      Araucania Region, Chile: potential risk for humans.
AB  - The concentrations of cadmium, lead, manganese and zinc were determined in the
      fish species Micropogonias manni captured in Budi Lake, Araucania Region (Chile).
      The measurements were made by atomic absorption spectroscopy, and the analysis
      considered the sex, weight and size of the species; the representative samples
      were taken from the liver and muscle tissue. The method was validated using
      certified reference material (DOLT-1). The ranges of concentrations found in the
      muscle tissue were: Cd, not determinate (n.d.)-0.26; Pb, n.d.-1.88; Mn, 0.02
      12.17 and Zn, 0.48-39.04 mg kg(-1) (dry weight). The concentrations in muscle
      tissue were generally lower than those found in the liver. With respect to the
      average concentrations recorded for each metal in the edible part of the fish
      (muscle tissue), it was found that the levels of Cd, Pb, Mn and Zn are within the
      ranges published by other authors in similar works and below the maximum
      concentration limits permitted by current legislation (FAO/WHO 2004; EU 2001) and
      do not constitute a health hazard for consumers of this species. The results were
      subjected to statistical analysis to evaluate the correlations between the
      content of the various metals and the sex, weight and size of each sample.

PMID- 21713479
TI  - Pesticide monitoring in The Netherlands: can it be improved?
AB  - In The Netherlands, pesticide monitoring of the surface water is separately
      managed by different water authorities. These water authorities can decide when,
      where, and what pesticide will be monitored and at what frequency. To help make
      the decisions more reasonable and make the monitoring system more efficient and
      systematic, three new types of monitoring maps were developed. The maps are based
      on actual pesticide measurement from current monitoring system and crop data.
      Combined temporal and spatial distribution maps give an overview of the pesticide
      problem in the whole Netherlands. It can be used to develop a strategy in which
      season and where the pesticide should be intensively monitored. Temporal
      distribution map, together with the pesticide usage prediction map, provide
      information of individual pesticide. They help to find out when and at what
      frequency and which pesticide be monitored, based on which monitoring facilities
      can be applied more efficiently.

PMID- 21713480
TI  - Using watershed characteristics, sediment, and tissue of resident mollusks to
      identify potential sources of trace elements to streams in a complex agricultural
      landscape.
AB  - Trace elements used in animal feed additives can be introduced to aquatic
      environments through application of manures from animal feeding operations to
      agricultural land as fertilizer. The use of poultry feed additives containing
      arsenic (As) is of particular concern in the Shenandoah River watershed
      (Virginia, USA), an agricultural landscape with a high density of poultry
      operations. This study investigated the relationship between watershed
      characteristics of Shenandoah River tributaries and trace element concentrations
      in streambed sediment and tissue of resident mollusks, including: Asian clams
      (Corbicula fluminea), which are commonly used biomonitors, and pleurocerid snails
      (Leptoxis carinata), which are generally understudied. Results failed to support
      the primary hypothesis of a predictive relationship between watershed densities
      of poultry operations and As concentrations in sediment and mollusk tissue.
      However, there were statistical relationships between land use in tributary
      watersheds and other trace elements in sediment (Cu, Mn, Pb, Zn) and tissue (Cd,
      Hg, Pb). Principal components analysis of the sediment data suggested a possible
      geologic source of As at some sites. Tissue concentrations of As were
      significantly higher in snails than in clams, but clams accumulated higher
      concentrations of other trace elements (Cd, Cr, Hg, Pb, Se). Snails may be useful
      biomonitors of environmental As, but appear to be less suitable than clams for
      studies of landscape sources of other trace elements.

PMID- 21713481
TI  - Greenhouse gas mitigation in rice-wheat system with leaf color chart-based urea
      application.
AB  - Conventional blanket application of nitrogen (N) fertilizer results in more loss
      of N from soil system and emission of nitrous oxide, a greenhouse gas (GHG). The
      leaf color chart (LCC) can be used for real-time N management and synchronizing N
      application with crop demand to reduce GHG emission. A 1-year study was carried
      out to evaluate the impact of conventional and LCC-based urea application on
      emission of nitrous oxide, methane, and carbon dioxide in a rice-wheat system of
      the Indo-Gangetic Plains of India. Treatments consisted of LCC scores of <=4 and
      5 for rice and wheat and were compared with conventional fixed-time N splitting
      schedule. The LCC-based urea application reduced nitrous oxide emission in rice
      and wheat. Application of 120 kg N per hectare at LCC <= 4 decreased nitrous
      oxide emission by 16% and methane by 11% over the conventional split application
      of urea in rice. However, application of N at LCC <= 5 increased nitrous oxide
      emission by 11% over the LCC <= 4 treatment in rice. Wheat reduction of nitrous
      oxide at LCC <= 4 was 18% as compared to the conventional method. Application of
      LCC-based N did not affect carbon dioxide emission from soil in rice and wheat.
      The global warming potential (GWP) were 12,395 and 13,692 kg CO(2) ha(-1) in LCC
      <= 4 and conventional urea application, respectively. Total carbon fixed in
      conventional urea application in rice-wheat system was 4.89 Mg C ha(-1) and it
      increased to 5.54 Mg C ha(-1) in LCC-based urea application (LCC <= 4). The study
      showed that LCC-based urea application can reduce GWP of a rice-wheat system by
      10.5%.

PMID- 21713482
TI  - Occurrence and characterization of selected organochlorine contaminants in
      outdoor dust collected from Xinxiang, a fast developing city in North China.
AB  - As facile "environmental media", the outdoor dust may reflect the changes of
      contaminants in environment more promptly. In the present study, selected
      organochlorine contaminants (OCs) include hexachlorocyclohexanes (HCHs),
      dichlorodiphenyltrichloroethanes (DDTs), hexachlorobenzene (HCB), and
      pentachlorobenzene (PeCB) were detected in 20 outdoor dust samples collected from
      Xinxiang City. The concentrations of SigmaHCHs, SigmaDDTs, HCB, and PeCB in dust
      were in the range of 0.18-5.05 ng/g dry weight, 0.44-13.50 ng/g dry weight, 0.13
      51.61 ng/g dry weight and ND-0.74 ng/g dry weight, respectively. Long-range
      transport, historical use, and recent impact of impure pesticides might be the
      main sources of OCs in the outdoor dust. The results of this study indicated that
      impure pesticide application maybe an important source of DDTs and HCB in the
      environment.

PMID- 21713483
TI  - The effects of pesticide mixtures on degradation of pendimethalin in soils.
AB  - Most agronomic situations involve a sequence of herbicide, fungicide, and
      insecticide application. On the other hand, use of pesticidal combinations has
      become a standard practice in the production of many agricultural crops. One of
      the most important processes influencing the behavior of a pesticide in the
      environment is its degradation in soil. It is known that due to several pesticide
      applications in one vegetation season, the pesticide may be present in mixtures
      with other pesticides or xenobiotics in soil. This study examines the role which
      a mixture of chemicals plays in pesticide degradation. The influence of other
      pesticides on the rate of pendimethalin (PDM) degradation in soil was measured in
      controlled conditions. Mixtures of PDM with mancozeb or mancozeb and thiamethoxam
      significantly influenced the degradation of pendimethalin under controlled
      conditions. The second type of mixtures, with metribuzin or thiamethoxam, did not
      affect the behavior of pendimethalin in soil. Also, we determined the influence
      of water content on the rate of pendimethalin degradation alone in two soils and
      compared it to the rate in three pesticide mixtures. We compared two equations to
      evaluate the predictors of the rate of herbicide dissipation in soil: the first
      order kinetic and the non-linear empirical models. We used the non-linear
      empirical model assuming that the degradation rate of a herbicide in soil is
      proportional to the difference of the observed concentration of herbicide in soil
      at time and concentration of herbicide in the last day of measurement.

PMID- 21713484
TI  - Spatial variability of soil 137Cs in the South Caspian region.
AB  - In a comprehensive program of environmental radioactivity survey in South Caspian
      region, (137)Cs inventories in soil has been measured at more than 50 sites in
      the Iranian northern province of Guilan. This has been the first wide-range
      survey of soil radionuclide inventories in the narrow band sensitive ecosystem of
      south Caspian shore. Radioactivity measurements were carried out using HPGe gamma
      spectrometry system. The activity concentration of (137)Cs in surface soil
      exhibits a mean value of 17.6 +/- 9.4 Bq kg(-1), with a range of 2.3-41.7 Bq kg(
      1). In many sites, split-level sampling method has been applied down to a depth
      of 20 cm. There were found generally two profiles. Most profiles exhibit a
      negative exponential distribution, while others revealed a clear subsurface peak
      in 5-10-cm layer. Cesium deposition in the study area has been estimated to be in
      the range of 0.38-2.9 kBq m(-2) with a mean value of 1.7 kBq m(-2). Distribution
      patterns of (137)Cs concentration levels and deposition values have been
      estimated using Kriging interpolation method. Observed hotspots in deposition
      pattern coincide with areas of higher precipitation.

PMID- 21713485
TI  - Detection of microcystins in Pamvotis lake water and assessment of cyanobacterial
      bloom toxicity.
AB  - Lake Pamvotis is a shallow, eutrophic Mediterranean lake with ecological
      significance. This paper deals with the evaluation of cyanobacterial toxicity in
      Lake Pamvotis. ELISA and HPLC revealed the presence of significant amounts of
      MCYST-LR. Danio rerio bioassay confirmed the toxic nature of the bloom.
      Cyanobacterial extracts had adverse toxic effects on development of D. rerio.
      Also, it was shown that cyanobacterial extracts containing environmentally
      detected concentrations of MCYST can cause reduced survival rate of fish species.
      The results clearly indicate that cyanobacterial blooms in Lake Pamvotis may be
      regarded as human and fish health hazard. Continuous monitoring of the lake is
      suggested, in order to prevent future possible intoxications.

PMID- 21713486
TI  - Environmental assessment of polycyclic aromatic hydrocarbons in the surface
      sediments of a remote region on the eastern coast, Taiwan.
AB  - Surface sediment samples were collected in He-Ping Harbor and the nearby He-Ping
      Estuary from 2005 to 2006 to examine spatial and temporal variability in
      polycyclic aromatic hydrocarbon (PAH) concentrations. The sum of the 16 USEPA
      priority pollutant PAHs varied from 8 to 312 ng/g dry weight, which was
      relatively low compared to values obtained from other studies in the world.
      Regarding temporal changes in the PAH profile, total PAH concentrations in the
      wet season were lower than during the dry season in He-Ping Harbor. However, the
      concentration of PAHs exhibited no significant difference in the four seasons in
      the He-Ping Estuary. PAH concentrations in He-Ping Harbor were higher than those
      in the He-Ping Estuary. In comparison with sediment quality guidelines, PAH
      concentrations of sediments in this study were lower than those outlined in the
      criteria, which suggests no evident adverse biological effects due to PAHs around
      the He-Ping coast. Ratios of specific PAH compounds calculated to assess the
      possible sources of PAHs reflect that PAHs in He-Ping Harbor may mainly be from
      pyrogenic coal combustion.

PMID- 21713487
TI  - Trace metals biogeochemistry of Kumaun Himalayan Lakes, Uttarakhand, India.
AB  - The increasing urbanization, along with tourism, has posed a major threat to the
      Kumaun Himalayan Lakes, Uttarakhand, India. The total metal concentration in the
      water, interstitial water, and sediments along with the metal fractionation
      studies were carried out to understand the remobilization of the trace metals
      from the sediments of the lakes. The high concentration of the metals in the
      water column of the lakes generally decreases with depth and the metals release
      from the sediment is mainly due to the prevalence of anoxic condition at the
      sediment-water interface and sediment column. The sediment shows that metals Fe
      and Cr are derived from detrital source, whereas Co, Ni, and Zn are derived
      mainly from the organic matter dissolution. The sparse correlation of the trace
      metals with Ti shows most of the metals have chiefly re-precipitated from the
      water column. The metals speciation studies also supports that metals experience
      a high rate of anoxic dissolution and their precipitation onto the sediments are
      determined by the sediment composition and organic matter content. The high
      concentration of manganese in the interstitial water in the lakes indicates
      dissolution of organic matter. The released manganese is adsorbed/precipitated as
      carbonate phase (Nainital Lake) and oxide pahse (in other lakes). The study shows
      that the trace metals are regenerated from the sediments due to oxyhydroxide
      dissolution and organic matter decomposition.

PMID- 21713488
TI  - Using the analytical hierarchy process to assess the environmental
      vulnerabilities of basins in Taiwan.
AB  - Every year, Taiwan endures typhoons and earthquakes; these natural hazards often
      induce landslides and debris flows. Therefore, watershed management strategies
      must consider the environmental vulnerabilities of local basins. Because many
      factors affect basin ecosystems, this study applied multiple criteria analysis
      and the analytical hierarchy process (AHP) to evaluate seven criteria in three
      phases (geographic phase, hydrologic phase, and societal phase). This study
      focused on five major basins in Taiwan: the Tan-Shui River Basin, the Ta-Chia
      River Basin, the Cho-Shui River Basin, the Tseng-Wen River Basin, and the Kao
      Ping River Basin. The objectives were a comprehensive examination of the
      environmental characteristics of these basins and a comprehensive assessment of
      their environmental vulnerabilities. The results of a survey and AHP analysis
      showed that landslide area is the most important factor for basin environmental
      vulnerability. Of all these basins, the Cho-Shui River Basin in central Taiwan
      has the greatest environmental vulnerability.

PMID- 21713489
TI  - Influence of water pollution on the growth and pigment concentration of the
      microalgae Phaeodactylum tricornutum Bohlin (Bacillariophyta).
AB  - The aim of the work was to study the influence of the water taken from one of the
      most polluted parts of the Peter the Great Bay (the Japan Sea), the Nakhodka Bay,
      on the growth and chlorophyll a concentration in the cells of microalga P.
      tricornutum Bohlin (Bacillariophyta). The estimation of the dynamics of cell
      number growth and chlorophyll a concentration in the cells of microalga grown in
      the water from the Nakhodka Bay was made. At the same time, in 2007-2008, the
      main hydrochemical parameters, such as water salinity, dissolved oxygen
      concentration, BOD(5), organic and mineral phosphates concentration, anionic
      surfactants, and total petroleum hydrocarbons, were determined. It is shown that
      in July 2007, when most hydrochemical parameters were lower than the maximum
      permissible level, the culture growth and chlorophyll a contents in the cells did
      not differ from the control for certain. In other seasons these indices differed
      greatly from the control. The positive correlation between the concentration of
      dissolved oxygen, phosphates, petroleum hydrocarbons, and the number of microalga
      cells, grown in the water from the Nakhodka Bay, was shown.

PMID- 21713490
TI  - Chloride migration in groundwater for a tannery belt in Southern India.
AB  - Groundwater in a tannery belt in Southern India is being polluted by the
      discharge of untreated effluents from 80 operating tanneries. Total dissolved
      solids and chloride (Cl(-)) measurements in open wells in the tannery cluster
      vary from 27,686 to 39,100 and 12,000 to 13,652 mg/l, respectively. A mass
      transport model was constructed using Visual MODFLOW Premium 4.4 software to
      investigate the chloride migration in an area of 75.56 km(2). Input to the
      chloride migration model was a groundwater flow model that considered steady and
      transient conditions. This model was calibrated with field observations; and
      sensitivity analysis was carried out whereby model parameters, viz.,
      conductivity, dispersivity, and source concentration were altered slightly, and
      the effect on calibration statistics was evaluated. Results indicated that
      hydraulic conductivity played a more sensitive role than did dispersivity. The
      Cl(-) migration was mainly through advection rather than dispersion. It was found
      that even if the pollutant load reduced to 50% of the present level, the Cl(-)
      concentration in groundwater, even after 6 years, would not be reduced to the
      permissible limit of drinking water in the tannery belt.

PMID- 21713491
TI  - Effects of roof and rainwater characteristics on copper concentrations in roof
      runoff.
AB  - Copper sheeting is a common roofing material used in many parts of the world.
      However, copper dissolved from roof sheeting represents a source of copper ions
      to watersheds. Researchers have studied and recently developed a simple and
      efficient model to predict copper runoff rates. Important input parameters
      include precipitation amount, rain pH, and roof angle. We hypothesized that the
      length of a roof also positively correlates with copper concentration (thus,
      runoff rates) on the basis that runoff concentrations should positively correlate
      with contact time between acidic rain and the copper sheet. In this study, a
      novel system was designed to test and model the effects of roof length (length of
      roof from crown to the drip edge) on runoff copper concentrations relative to
      rain pH and roof angle. The system consisted of a flat-bottom copper trough
      mounted on an apparatus that allowed run length and slope to be varied. Water of
      known chemistry was trickled down the trough at a constant rate and sampled at
      the bottom. Consistent with other studies, as pH of the synthetic rainwater
      decreased, runoff copper concentrations increased. At all pH values tested, these
      results indicated that run length was more important in explaining variability in
      copper concentrations than was the roof slope. The regression equation with log
      transformed data (R(2) = 0.873) accounted for slightly more variability than the
      equation with untransformed data (R(2) = 0.834). In log-transformed data, roof
      angle was not significant in predicting copper concentrations.

PMID- 21713492
TI  - Water pinch analysis for water and wastewater minimization in Tehran oil refinery
      considering three contaminants.
AB  - This study aims to find an appropriate way to minimize water utility in the
      petrochemical and petroleum industries due to high rate of water consumption. For
      this purpose, Tehran oil refinery has been well studied. In this research, three
      key contaminants including suspended solid, hardness as well as COD have been
      considered to analyze the water network. In addition, the potential of water
      reuse was studied for all methods. These key contaminants once were analyzed
      separately as a single contaminant and the amount of required freshwater was
      calculated for them. In this stage, amount of freshwater was reduced to about
      60.9 (17%), 203 (59.7%) and 143 m(3)/h (42.5%) in terms of suspended solids,
      hardness, and COD, respectively. Water minimization within operations for
      suspended solids is less than two others. Therefore, this is a limiting
      contaminant and can be selected as a key contaminant. In the next stage, three
      contaminants were analyzed two by two based on their mass transfer. Results show
      that, in the targeting for minimization based on the suspended solids and
      hardness, the amount of required water is reduced to 142.74 m(3)/h or 42%. This
      amount for suspended solids and COD is equal to 86.3 m(3)/h (26%) and for COD and
      hardness is 124 m(3)/h (37%). Analyzing the methods shows that the method based
      on the double contaminant gives more precise results rather than single
      contaminant.

PMID- 21713493
TI  - Water pollution in relation to mineral exploration: a case study from Alayi-Ovim
      area of southeastern Nigeria.
AB  - Water samples from rivers, streams, springs, and shallow wells in Alayi-Ovim area
      of southeast Nigeria have been analyzed for Pb, Ca, Mg, Fe, Mg, PO(4), NO(3),
      CO(3), SO(4), Cl, and pH. The analyses were carried out using atomic absorption
      spectrometer and Hach Direct Reading Equipment. Results of the analyses from the
      area conform to the WHO (1995) standards for drinking water. However, the results
      show relative enrichment of Ca, pH, Mg, CO(3), and Cl. Low values were obtained
      for Fe, SO(4), and NO(3). While the Cl and Pb enrichment in the area north of
      Alayi-Ovim axis is attributed to proximity to the lead-zinc and chloride-rich
      formations of the Turonian Eze-Aku and the Albian Asu River; the Ca, Mg, SO(4),
      and CO(3) enrichment in Southern part of Alayi-Ovim is due to the limestone
      bearing Late Maastrichtian Nsukka Formation. Furthermore, the very low values of
      less than 5 ppm for these characters in water in the central region correlate
      well with the relatively clean Maastrichtian quartz arenite Ajali Sandstone
      Formation. The Pb-Zn and Cl incursions into the water system from the Older
      Albian Asu River/Turonian Eze-Aku Formations in the northern part of Alayi-Ovim
      area and the leaching of Mg, and Ca into the water system in the Maastrichtian
      limestone area in the south thus constitute geochemical indices for chemical
      pollution and mineral exploration for brine and dolomitic limestone in the area.

PMID- 21713494
TI  - Physicochemical and microbiological assessment of recreational and drinking
      waters.
AB  - The present study was aimed to make an assessment of health risk due to pollution
      and human pathogenic bacteria associated with the recreational and drinking water
      sources in twin densely populated holy Indian cities Ayodhya and Faizabad. Though
      physicochemical studies revealed that the water available in the area is under
      recommended limits for human use, it is unsafe on account of poor microbiological
      quality of surface and ground water in the region. The most probable number (MPN)
      test results revealed the preponderance of >=2,400 total coliforms (TC) (100 ml)(
      1) in river, pond, dug well and kund waters. Contrary to that, 94% tube wells,
      32% hand pumps and 25% piped supply water were under safe limits having <3 TC
      (100 ml)(-1). The shallow depth (~40 ft), water logging and presence of septic
      tanks in the near vicinity are the possible reasons of poor microbial quality of
      hand pump drinking water. The municipal supply water passes along sewage line
      where loose connections and/or cracks in pipe lead to mixing and contamination.
      The significant best quality of tube well water evident from the absence of TC
      could be attributed to the depth of well >=150 ft and usually their location away
      from the habitation. A total of 263 bacteria from 186 water samples were
      isolated, and at least five genera of enteric bacteria from various water sources
      were identified morphologically and biochemically as Escherichia coli, Klebsiella
      sp., Enterobacter sp., Shigella sp. and Salmonella sp. The serotyping of 72 E.
      coli and 36 Salmonella sp. revealed 51 as E. coli O157 and 20 as Salmonella sp.
      The presence of enteric pathogens in water sources pose threat to human health
      and therefore call for immediate remedial measures.

PMID- 21713495
TI  - Mixed response in bacterial and biochemical variables to simulated sand mining in
      placer-rich beach sediments, Ratnagiri, West coast of India.
AB  - We investigated the influence on bacterial community and biochemical variables
      through mechanical disturbance of sediment-akin to small-scale mining in
      Kalbadevi beach, Ratnagiri, a placer-rich beach ecosystem which is a potential
      mining site. Changes were investigated by comparing three periods, namely phase I
      before disturbance, phase II just after disturbance, and phase III 24 h after
      disturbance as the bacterial generation time is <=7 h. Cores from dune, berm,
      high-, mid-, and low-tide were examined for changes in distribution of total
      bacterial abundance, total direct viability (counts under aerobic and anaerobic
      conditions), culturability and biochemical parameters up to 40 cm depth. Results
      showed that bacterial abundance decreased by an order from 10(6) cells g(-1)
      sediment, while, viability reduced marginally. Culturability on different
      strength nutrient broth increased by 155% during phase II. Changes in sedimentary
      proteins, carbohydrates, and lipids were marked at berm and dune and masked at
      other levels by tidal influence. Sedimentary ATP reduced drastically. During
      phase III, Pearson's correlation between these variables evolved from non
      significant to significant level. Thus, simulated disturbance had a mixed effect
      on bacterial and biochemical variables of the sediments. It had a negative impact
      on bacterial abundance, viability and ATP but positive impact on culturability.
      Viability, culturability, and ATP could act as important indicators reflecting
      the disturbance in the system at short time intervals. Culturability, which
      improved by an order, could perhaps be a fraction that contributes to restoration
      of the system at bacterial level. This baseline information about the potential
      mining site could help in developing rational approach towards sustainable
      harnessing of resources with minimum damage to the ecosystem.

PMID- 21713496
TI  - Particle emission from heavy-duty engine fuelled with blended diesel and
      biodiesel.
AB  - In this study, particulate matter (PM) were characterized from a place impacted
      by heavy-duty vehicles (Bus Station) fuelled with diesel/biodiesel fuel blend
      (B3) in the city of Londrina, Brazil. Sixteen priority polycyclic aromatic
      hydrocarbons (PAH) concentrations were analyzed in the samples by their
      association with atmospheric PM, mass size distributions and major ions
      (fluorite, chloride, bromide, nitrate, phosphate, sulfate, nitrite, oxalate;
      fumarate, formate, succinate and acetate; lithium, sodium, potassium, magnesium,
      calcium and ammonium). Results indicate that major ions represented 21.2%
      particulate matter mass. Nitrate, sulfate, and ammonium, respectively, presented
      the highest concentration levels, indicating that biodiesel may also be a
      significant source for these ions, especially nitrate. Dibenzo[a,h]anthracene and
      indeno[1,2,3,-cd]pyrene were the main PAH found, and a higher fraction of PAH
      particles was found in diameters lower than 0.25 MUm in Londrina bus station. The
      fine and ultrafine particles were dominant among the PM evaluated, suggesting
      that biodiesel decreases the total PAH emission. However, it does also increase
      the fraction of fine and ultrafine particles when compared to diesel.

PMID- 21713497
TI  - Heavy metals and arsenic concentrations in ten fish species from the Salek lakes
      (Slovenia): assessment of potential human health risk due to fish consumption.
AB  - The study, which measured the concentrations of Hg, Pb, Cd, Zn and As in various
      fish tissues (muscle, gill and liver) of 10 fish species (Abramis brama danubii,
      Alburnus alburnus alburnus, Barbus meridionalis petenyi, Carassius auratius
      gibelio, Cyprinus carpio, Lepomis gibossus, Leuciscius cephalus cephalus, Perca
      fluviatilis fluviatilis, Rutilus rutilus, Scardinus erythrophtlalmus
      erythrophtlalmus) collected in the Salek lakes, is the first survey regarding
      metal concentrations in fish species with samples originating from Slovene lakes,
      while only a limited number of such studies have been carried out in southeastern
      Europe. Since these lakes are situated in the close vicinity of the largest
      Slovene thermal power plant, the study provides an insight into the potential
      impact of increased levels of metals in the environment as well as an estimate of
      the contamination of fish tissues with metals. Furthermore, it was possible to
      compare the results obtained with those from other studies regarding metal levels
      in freshwater fish species. The mean metal concentrations of different tissues
      irrespective of species varied in the following ranges: Zn 4.31-199 mg/kg ww, Pb
      0.01-0.48 mg/kg ww, As 0.02-0.44 mg/kg ww, Hg <0.01-0.31 mg/kg ww, Cd < 0.01-0.19
      mg/kg ww. In general, higher contents of Hg were found in muscles and livers than
      in gills and higher contents of As in gills and livers than in muscles,
      respectively. The accumulation of Pb and Zn was most pronounced in gills. The
      result obtained regarding metal concentrations in fish revealed that the
      ecosystems of the Salek lakes are not polluted with Hg and Pb, slightly loaded
      with As and Cd and moderately polluted with Zn. In addition, the potential human
      health risk due to fish consumption was assessed. This showed that the estimated
      weekly intakes for all metals were far below provisional permissible tolerable
      weekly intakes determined by WHO/FAO. The consumption of fish from the Salek
      lakes, therefore, does not pose a risk to human health.

PMID- 21713498
TI  - Arsenic accumulation in native plants of West Bengal, India: prospects for
      phytoremediation but concerns with the use of medicinal plants.
AB  - Arsenic (As) is a widespread environmental and food chain contaminant and class
      I, non-threshold carcinogen. Plants accumulate As due to ionic mimicry that is of
      importance as a measure of phytoremediation but of concern due to the use of
      plants in alternative medicine. The present study investigated As accumulation in
      native plants including some medicinal plants, from three districts [Chinsurah
      (Hoogly), Porbosthali (Bardhman), and Birnagar (Nadia)] of West Bengal, India,
      having a history of As pollution. A site-specific response was observed for
      Specific Arsenic Uptake (SAU; mg kg(-1) dw) in total number of 13 (8 aquatic and
      5 terrestrial) collected plants. SAU was higher in aquatic plants (5-60 mg kg(-1)
      dw) than in terrestrial species (4-19 mg kg(-1) dw). The level of As was lower in
      medicinal plants (MPs) than in non-medicinal plants, however it was still beyond
      the WHO permissible limit (1 mg kg(-1) dw). The concentration of other elements
      (Cu, Zn, Se, and Pb) was found to be within prescribed limits in medicinal plants
      (MP). Among the aquatic plants, Marsilea showed the highest SAU (avg. 45 mg kg(
      1) dw), however, transfer factor (TF) of As was the maximum in Centella asiatica
      (MP, avg. 1). Among the terrestrial plants, the maximum SAU and TF were
      demonstrated by Alternanthera ficoidea (avg. 15) and Phyllanthus amarus (MP, avg.
      1.27), respectively. In conclusion, the direct use of MP or their by products for
      humans should not be practiced without proper regulation. In other way, one fern
      species (Marsilea) and some aquatic plants (Eichhornia crassipes and Cyperus
      difformis) might be suitable candidates for As phytoremediation of paddy fields.

PMID- 21713499
TI  - Night-sky brightness monitoring in Hong Kong: a city-wide light pollution
      assessment.
AB  - Results of the first comprehensive light pollution survey in Hong Kong are
      presented. The night-sky brightness was measured and monitored around the city
      using a portable light-sensing device called the Sky Quality Meter over a 15
      month period beginning in March 2008. A total of 1,957 data sets were taken at
      199 distinct locations, including urban and rural sites covering all 18
      Administrative Districts of Hong Kong. The survey shows that the environmental
      light pollution problem in Hong Kong is severe-the urban night skies (sky
      brightness at 15.0 mag arcsec(- 2)) are on average ~ 100 times brighter than at
      the darkest rural sites (20.1 mag arcsec(- 2)), indicating that the high lighting
      densities in the densely populated residential and commercial areas lead to light
      pollution. In the worst polluted urban location studied, the night-sky at 13.2
      mag arcsec(- 2) can be over 500 times brighter than the darkest sites in Hong
      Kong. The observed night-sky brightness is found to be affected by human factors
      such as land utilization and population density of the observation sites,
      together with meteorological and/or environmental factors. Moreover, earlier
      night skies (at 9:30 p.m. local time) are generally brighter than later time (at
      11:30 p.m.), which can be attributed to some public and commercial lightings
      being turned off later at night. On the other hand, no concrete relationship
      between the observed sky brightness and air pollutant concentrations could be
      established with the limited survey sampling. Results from this survey will serve
      as an important database for the public to assess whether new rules and
      regulations are necessary to control the use of outdoor lightings in Hong Kong.

PMID- 21713500
TI  - Inventory methods for trees in nonforest areas in the Great Plains States.
AB  - The US Forest Service's Forest Inventory and Analysis (FIA) program collects
      information on trees in areas that meet its definition of forest. However, the
      inventory excludes trees in areas that do not meet this definition, such as those
      found in urban areas, in isolated patches, in areas with sparse or predominantly
      herbaceous vegetation, in narrow strips (e.g., shelterbelts), or in riparian
      areas. In the Great Plains States, little is known about the tree resource in
      these noninventoried, nonforest areas, and there is a great deal of concern about
      the potential impact of invasive pests, such as the emerald ash borer. To address
      this knowledge gap, FIA's National Inventory and Monitoring Applications Center
      has partnered with state cooperators and others in a project called the Great
      Plains Initiative to design and implement an inventory of trees in nonforest
      areas. The goal of the inventory is to characterize the nonforest tree resource
      using methods compatible with those of FIA so a holistic understanding of the
      resource can be obtained by integrating the two surveys. The goal of this paper
      is to describe the process of designing and implementing the survey, including
      plot and sample design, and to present some example results from a reporting tool
      we developed.

PMID- 21713501
TI  - The effects of socioeconomic parameters on household solid-waste generation and
      composition in developing countries (a case study: Ahvaz, Iran).
AB  - Environment problems associated with the generation of waste are part of societal
      changes where households play an important role. These societal changes influence
      the size, structure and characteristic of given households. For the effective
      planning of solid-waste handling infrastructure, it is essential to know the
      quantity of waste generation and its composition. This paper presents the
      findings of a study carried out in an urban municipal area in Iran to determine
      the household solid-waste generation rate and waste composition based on field
      surveys and to determine the related socioeconomic parameters. The dependent
      variables were waste generation and composition, and independent variables were
      family size, family employment, age, number of room and education. Over 400
      sample households were selected for the study using a stratified random sampling
      methodology and from five different socioeconomic groups. Waste collected from
      all groups of households were segregated and weighted. Waste generation rate was
      5.4 kg/household/day. Household solid waste comprised of ten categories of wastes
      and with the largest component (76.9%). The generation and composition of
      household solid waste were correlated with family size, education level and
      households income. This paper adequately suggests new insights concerning the
      role of socioeconomic parameters in affecting the generation of household waste.

PMID- 21713502
TI  - The monitoring results of electromagnetic radiation of 110-kV high-voltage lines
      in one urban location in Chongqing P.R. China.
AB  - To understand electromagnetic radiation field strength and its influencing
      factors of certain 110-kV high-voltage lines in one urban area of Chongqing by
      measuring 110-kV high-voltage line's electromagnetic radiation level. According
      to the methodology as determined by the National Hygienic Standards, we selected
      certain adjacent residential buildings, high-voltage lines along a specific
      street and selected different distances around its vertical projection point as
      monitoring points. The levels of electromagnetic radiations were measured
      respectively. In this investigation within the frequency of 5-1,000 Hz both the
      electric field strength and magnetic field strength of each monitoring sites were
      lower than the public exposure standards as determined by the International
      Commission on Non-Ionizing Radiation Protection. However, the electrical field
      strength on the roof adjacent to the high-voltage lines was significantly higher
      than that as measured on the other floors in the same buildings (p < 0.05). The
      electromagnetic radiation measurements of different monitoring points, under the
      same high-voltage lines, showed the location which is nearer the high-voltage
      line maintain a consistently higher level of radiation than the more distant
      locations (p < 0.05). Electromagnetic radiation generated by high-voltage lines
      decreases proportionally to the distance from the lines. The buildings can to
      some extent shield (or absorb) the electric fields generated by high-voltage
      lines nearby. The electromagnetic radiation intensity near high-voltage lines may
      be mitigated or intensified by the manner in which the high-voltage lines are set
      up, and it merits attention for the potential impact on human health.

PMID- 21713503
TI  - Responses of human soleus motor units to low-threshold stimulation of the tibial
      nerve.
AB  - The peristimulus frequencygram (PSF) has recently been shown to illustrate
      postsynaptic potentials of motoneurones much more reliably than the peristimulus
      time histogram (PSTH). The aim of this investigation was to examine the profile
      of the postsynaptic potential (PSP) in soleus motoneurones in response to an H
      reflex with and without accompanying M waves of different magnitude by using PSTH
      and PSF profiles of single motor units. Nine men and five women healthy subjects
      participated in this study. Electrical stimuli were delivered to the tibial nerve
      in the popliteal fossa. The reflex response of the soleus muscle was recorded
      using both surface electromyogram and single motor unit potentials. The PSTH
      analysis demonstrated that there were four different synaptic events following
      low-intensity stimulation of the tibial nerve: primary enhancement in firing
      probability (H-reflex or E1), primary reduction in firing probability (primary
      silent period or SP1), secondary reduction in firing probability (secondary
      silent period or SP2), and secondary enhancement in firing probability (E2). On
      the other hand, the PSF analysis indicated only two reflex responses, long
      lasting enhancement in discharge rate including the H-reflex (LLE) and long
      lasting decrease in discharge rate (LLD). The results of the two analyses methods
      are compared and contrasted. While the PSTH demonstrated that there was a silent
      period (SP1) immediately following the H-reflex, the PSF indicated an increase in
      discharge rate during the same period. The PSF also indicated that, during SP2
      and E2, the discharge rate actually decreased (LLD). It was therefore suggested
      that LLD involved activation of several inhibitory pathways including the
      autogenic inhibition of units via the Golgi tendon organs. It was concluded that
      the PSF could indicate the details of the postsynaptic potentials and is very
      useful for bringing out previously unknown effects of electrical stimulation of
      muscle nerves.

PMID- 21713504
TI  - Tool-use learning by common marmosets (Callithrix jacchus).
AB  - One of the most critical and common features of tool use is that the tool
      essentially functions as a part of the body. This feature is likely rooted in
      biological features that are shared by tool users. To establish an ideal primate
      model to explore the neurobiological mechanisms supporting tool-use behaviours,
      we trained common marmosets, a small New World monkey species that is not usually
      associated with tool use, to use a rake-shaped tool to retrieve food. Five naive
      common marmosets were systematically trained to manipulate the tool using a 4
      stage, step-by-step protocol. The relative positions of the tool and the food
      were manipulated, so that the marmosets were required to (1) pull the tool
      vertically, (2) move the tool horizontally, (3) make an arc to retrieve a food
      item located behind the tool and (4) retrieve the food item. We found
      considerable individual differences in tool-use technique; for example, one
      animal consistently used a unilateral hand movement for all of the steps, whereas
      the others (n = 4) used both hands to move the tool depending on the location of
      the food item. After extensive training, all of the marmosets could manipulate
      the rake-shaped tool, which is reported in this species for the first time. The
      common marmoset is thus a model primate for such studies. This study sets the
      stage for future research to examine the biological mechanisms underlying the
      cognitive ability of tool use at the molecular and genetic levels.

PMID- 21713505
TI  - Melatonin for sleep-disturbed children with autism spectrum disorders: can we
      really speak of a substitution treatment?

PMID- 21713506
TI  - Trajectories of CBCL attention problems in childhood.
AB  - The first aim of this study was to identify developmental trajectories of
      Attention Problems in twins followed from age 6 to 12 years. Second, we
      investigated whether singletons follow similar trajectories. Maternal
      longitudinal ratings on the Attention Problems (AP) subscale of the Child
      Behavior Checklist were obtained for a sample of 12,486 twins from the
      Netherlands Twin Register and for a general population sample of 1,346
      singletons. Trajectories were analyzed by growth mixture modeling in twins, and
      compared with singletons. Teacher ratings on the AP subscale of the Teachers'
      Report Form were available for 7,179 twins and 1,211 singletons, and were used
      for cross-sectional mean comparisons at each age. All analyses were conducted for
      boys and girls separately. We identified three linear trajectories in both boys
      and girls, i.e., stable low (62-71%), low-increasing (15-18%), and high
      decreasing (14-21%). Singletons followed three identical trajectories, with
      similar class proportions. Teacher ratings yielded no differences in mean levels
      of Attention Problems between twins and singletons. The development of Attention
      Problems from age 6 to 12 years can be characterized by stable low, low
      increasing, and high-decreasing developmental trajectories. Twins and singletons
      are comparable with respect to the development of Attention Problems in
      childhood.

PMID- 21713507
TI  - Epidemiology of psychoactive drug use amongst adolescents in metropolitan Lagos,
      Nigeria.
AB  - The study was conducted in response to the lack of epidemiological data in recent
      time on the use of psychoactive substances by adolescents in metropolitan Lagos-a
      city unique for its socio-economic profile. We considered some methodological
      issues omitted in several previous studies. A total of 4,286 school pupils (mean
      age 15.2) were anonymously administered a Self-Report Questionnaire to ascertain
      a range of key drug use factors in lifetime and 1-year periods. The rate of use
      of most of the 14 substances investigated was much higher than reported in any
      other study on comparable population sample. We found that 61.8 and 32.1% of
      respondents have used one or more substances in their lifetime and in the past 1
      year, respectively. High lifetime rates of use were found for common stimulants:
      coffee, kolanut, and prescription drugs (barbiturates and minor tranquilisers).
      The rate of use of proscribed addictive substances, cannabis, heroin, and
      cocaine, ranged between 4.0 and 4.8%. Missing data and non-response rates were
      few; however, social acquiescence, under and over reporting, could be mitigant to
      estimation of rates and patterns of use. We advocate properly articulated school
      based educative programmes that can facilitate drug demand reduction.

PMID- 21713508
TI  - Overexpression of the ABC transporter AvtAB increases avermectin production in
      Streptomyces avermitilis.
AB  - Avermectins are 16-membered macrocyclic polyketides with potent antiparasitic
      activities, produced by Streptomyces avermitilis. Upstream of the avermectin
      biosynthetic gene cluster, there is the avtAB operon encoding the ABC transporter
      AvtAB, which is highly homologous to the mammalian multidrug efflux pump P
      glycoprotein (Pgp). Inactivation of avtAB had no effect, but increasing the
      concentration of avtAB mRNA 30-500-fold, using a multi-copy plasmid in S.
      avermitilis, enhanced avermectin production about two-fold both in the wild-type
      and in a high-yield producer strain on agar plates. In liquid industrial
      fermentation medium, the overall productivity of avermectin B1a in the engineered
      high-yield producer was improved for about 50%, from 3.3 to 4.8 g/l. In liquid
      YMG medium, moreover, the ratio of intracellular to extracellular accumulation of
      avermectin B1a was dropped from 6:1 to 4.5:1 in response to multiple copies of
      avtAB. Additionally, the overexpression of avtAB did not cause any increased
      expression of the avermectin biosynthetic genes through RT-PCR analysis. We
      propose that the AvtAB transporter exports avermectin, and thus reduces the
      feedback inhibition on avermectin production inside the cell. This strategy may
      be useful for enhancing the production of other antibiotics.

PMID- 21713509
TI  - Biotransformation of acetamiprid by the white-rot fungus Phanerochaete sordida YK
      624.
AB  - Acetamiprid (ACE) belongs to the neonicotinoid class of systemic broad-spectrum
      insecticides, which are the most highly effective and largest-selling
      insecticides worldwide for crop protection. As neonicotinoid insecticides persist
      in crops, biotransformation of these insecticides represents a promising approach
      for improving the safety of foods. Here, the elimination of ACE from a liquid
      medium by the white-rot fungus Phanerochaete sordida YK-624 was examined. Under
      ligninolytic and non-ligninolytic conditions, 45% and 30% of ACE were eliminated,
      respectively, after 15 days of incubation. High-resolution electrospray
      ionization mass spectra and nuclear magnetic resonance analyses of a metabolite
      identified in the culture supernatant suggested that ACE was N-demethylated to
      (E)-N (1)-[(6-chloro-3-pyridyl)-methyl]-N (2)-cyano-acetamidine, which has a much
      lower toxicity than ACE. In addition, we investigated the effect of the
      cytochrome P450 inhibitor piperonyl butoxide (PB) on the elimination of ACE. The
      elimination rate of ACE by P. sordida YK-624 was markedly reduced by the addition
      of either 0.01 or 0.1 mM PB to the culture medium. These results suggest that
      cytochrome P450 plays an important role in the N-demethylation of ACE by P.
      sordida YK-624.

PMID- 21713510
TI  - Engineering Escherichia coli for efficient cellobiose utilization.
AB  - Escherichia coli normally cannot utilize the beta-glucoside sugar cellobiose as a
      carbon and energy source unless a stringent selection pressure for survival is
      present. The cellobiose-utilization phenotype can be conferred by mutations in
      the two cryptic operons, chb and asc. In this study, the cellobiose-utilization
      phenotype was conferred to E. coli by replacing the cryptic promoters of these
      endogenous operons with a constitutive promoter. Evolutionary adaptation of the
      engineered strain CP12CHBASC by repeated subculture in cellobiose-containing
      minimal medium led to an increase in the rate of cellobiose uptake and cell
      growth on cellobiose. An efficient cellobiose-metabolizing E. coli strain would
      be of great importance over glucose-metabolizing E. coli for a simultaneous
      saccharification and fermentation process, as the cost of the process would be
      reduced by eliminating one of the three enzymes needed to hydrolyze cellulose
      into simple sugars.

PMID- 21713511
TI  - Identification of a periplasmic AlgK-AlgX-MucD multiprotein complex in
      Pseudomonas aeruginosa involved in biosynthesis and regulation of alginate.
AB  - The opportunistic human pathogen Pseudomonas aeruginosa produces an extracellular
      polysaccharide called alginate. This is especially relevant in pulmonary
      infection of cystic fibrosis patients where it protects the bacteria from the
      hosts' immune system and the diffusion of antibiotics. Here a connection between
      the stability of a proposed alginate polymerisation/secretion complex and the
      regulation of the operon encoding these proteins was assessed. Experimental
      evidence was provided for a periplasmic multiprotein complex composed of AlgX,
      AlgK, and the regulatory protein MucD. Disruption of the alginate machinery in a
      mucoid strain, either by removal, or over production of various essential
      proteins resulted in an at least 2-fold increase in transcription of a lacZ
      reporter under the control of the algD promoter. Instability of the complex was
      indicated by an increase in secretion of alginate degradation products. This
      increase in transcription was found to be dependent on the negative regulatory
      protein MucD. Surprisingly, over production of MucD leads to a 3.3-fold increase
      in transcription from the alginate promoter and a 1.7-fold increase in the levels
      of alginate produced, suggesting an additional positive regulatory role for MucD
      in mucoid strains. Overall, this study provided experimental evidence for the
      proposed periplasmic multiprotein complex and established a link of a constituent
      of this complex, MucD, to transcriptional regulation of alginate biosynthesis
      genes.

PMID- 21713512
TI  - Poly(aspartate) hydrolases: biochemical properties and applications.
AB  - Thermally synthesized poly(aspartate) (tPAA) shows potential for use in a wide
      variety of products and applications as a biodegradable replacement for non
      biodegradable polycarboxylates, such as poly(acrylate). The tPAA molecule has
      unnatural structures, and the relationship between its biodegradability and
      structures has been investigated. Two tPAA-degrading bacteria, Sphingomonas sp.
      KT-1 and Pedobacter sp. KP-2, were isolated from river water; from them, two PAA
      hydrolyzing enzymes, PAA hydrolases-1 and -2, were purified and biologically and
      genetically characterized. Interestingly, not only are PAA hydrolases-1 from
      those two strains novel in terms of structural genes and substrate specificities
      (they specifically cleave the amide bond between beta-aspartate units in tPAA),
      they also probably play a central role in tPAA biodegradation by both strains. In
      green polymer chemistry, one active area of research is the use of purified
      enzymes for the enzyme-catalyzed synthesis of polypeptides by taking advantage of
      their substrate specificities. Recently, beta-peptides have attracted academic
      and industrial interest as functional materials as they possess both functions of
      alpha-peptides and excellent metabolic stability. As one of the attractive
      applications of PAA hydrolases, we report here the enzyme-catalyzed synthesis of
      poly(alpha-ethyl beta-aspartate), which is composed of only beta-linkages and
      belongs to beta-peptides, using the unique substrate specificity of the enzyme
      from Pedobacter sp. KP-2.

PMID- 21713513
TI  - Large-scale expression, purification, and glucose uptake activity of recombinant
      human FGF21 in Escherichia coli.
AB  - As a novel important regulator of glucose and lipid metabolism homeostasis, human
      fibroblast growth factor 21 (hFGF21) has become a potential drug candidate for
      the treatment of metabolic diseases including obesity, and type 2 diabetes, as
      well as non-alcoholic fatty liver disease. To improve the production of
      recombinant hFGF21 to meet the increasing demand in clinical applications, an
      artificial gene encoding its mature peptide sequence was constructed, cloned into
      vector pET-3c and then expressed in Escherichia coli Origami B (DE3). Under
      optimal conditions in a 50-L fermentor, the average bacterial yield and the
      soluble expression level of recombinant hFGF21 of six batches attained 1750 +/-
      185 g and 32 +/- 1.5%, respectively. The target protein was purified by the
      combination of nickel-nitrilotriacetic acid affinity chromatography and Sephadex
      S-100 resin. 5% (w/v) trehalose solution was able to prevent rhFGF21 from
      degradation effectively. The purity of rhFGF21 was higher than 97%, and the yield
      was 213 +/- 17 mg/L. The preliminary biochemical characterization of rhFGF21 was
      confirmed using Western blot and peptide map finger analysis. Based on the
      glucose oxidase-peroxidase assay, the EC50 of glucose uptake activity of the
      purified rhFGF21 was 22.1 nM.

PMID- 21713514
TI  - High-level production of a kringle domain variant by high-cell-density
      cultivation of Escherichia coli.
AB  - Human kringle domains (KDs) are ubiquitously expressed binding modulators that
      fold into seven flexible loops and it has been previously demonstrated that KDs
      can be engineered toward target-specific binding proteins as a non-antibody
      protein scaffold. Here, we report a method for efficient expression of a KD
      derivative (KD548)-a promising anti-cancer agent-by high-cell-density culture of
      Escherichia coli at a preparative scale production. The correct folding of KD548
      requires three disulfide bonds. Nevertheless, cytoplasmic expression of KD548 in
      E. coli led to good yields of highly soluble proteins with high activity. For
      efficient expression, four sets of expression systems consisting of different
      promoters (lac or T7) and fusion tags (His or FLAG) were examined. Of these, the
      expression system using a combination of the T7 promoter with the FLAG tag
      resulted in the highest production in shake flask cultivation as well as in high
      cell-density cultivation performed in a 6.6-L jar bioreactor. When protein
      expression was induced at high-cell density (optical density [OD] = 100) and when
      complex feeding solutions were supplemented, cell density (maximum OD = 184) and
      production yield (approximately 5.4 g/L) were significantly enhanced to values
      that were much higher than those found previously with Pichia cultivation (<8
      mg/L).

PMID- 21713515
TI  - Identification and comparison of cutinases for synthetic polyester degradation.
AB  - Cutinases have been exploited for a broad range of reactions, from hydrolysis of
      soluble and insoluble esters to polymer synthesis. To further expand the
      biotechnological applications of cutinases for synthetic polyester degradation,
      we perform a comparative activity and stability analysis of five cutinases from
      Alternaria brassicicola (AbC), Aspergillus fumigatus (AfC), Aspergillus oryzae
      (AoC), Humicola insolens (HiC), and the well-characterized Fusarium solani (FsC).
      Of the cutinases, HiC demonstrated enhanced poly(epsilon-caprolactone) hydrolysis
      at high temperatures and under all pH values, followed by AoC and AfC. Both AbC
      and FsC are least stable and function poorly at high temperatures as well as at
      acidic pH conditions. Surface charge calculations and phylogenetic analysis
      reveal two important modes of cutinase stabilization: (1) an overall neutral
      surface charge within the "crowning area" by the active site and (2) additional
      disulfide bond formation. These studies provide insights useful for reengineering
      such enzymes with improved function and stability for a wide range of
      biotransformations.

PMID- 21713516
TI  - 3D dynamic position assessment of the coronary sinus lead in cardiac
      resynchronization therapy.
AB  - Although cardiac resynchronization therapy (CRT) is an effective treatment for
      chronic systolic heart failure with dyssynchrony, about one-third of patients do
      not respond favorably. The interaction between the pacing lead and the coronary
      sinus (CS) branches is of paramount importance for an effective
      resynchronization. Minor changes in lead position overtime could interfere with
      CRT mechanics, without affecting even biophysical parameters or ECG morphology.
      Although late post-implant CS lead dislodgement rate is consistent, lead
      movements have been little investigated and only with bi-dimensional methods. The
      aim of this study was (1) to develop a method for quantifying CS lead position in
      the 3D domain throughout the cardiac cycle and (2) to test it by comparing the CS
      lead position at implant and at follow-up, using chest fluoroscopy. Method
      performance, its accuracy and reproducibility were qualitatively and
      quantitatively assessed. Intra- and inter-observer percent discordance between
      trajectories were also computed. The accuracy of the procedure resulted in 0.3 +/
      0.1 mm and its resolution was 0.5 mm. Intra- and inter-observer discordances
      were 2.2 +/- 1.5 and 5.5 +/- 3.6 mm, respectively. The proposed method for
      measuring the CS lead dynamic placement in 3D space seems accurate and
      reproducible. Investigating CS lead 3D dynamics could provide further insights
      into CRT mechanics.

PMID- 21713517
TI  - Clinical impact of fluvoxamine-mediated long QTU syndrome.

PMID- 21713518
TI  - New users of antidepressant medications: first episode duration and predictors of
      discontinuation.
AB  - PURPOSE: Clinical guidelines recommend that antidepressant treatment should be
      continued for at least 6 months. We examined persistence in patients initiated on
      an antidepressant medication and factors associated with treatment cessation.
      METHODS: We conducted a cohort study of antidepressant initiators in the
      Australian veteran population. Patients included were those who had filled at
      least one prescription for an antidepressant between 2005 and 2008 but had no
      antidepressants in the preceding 12 months. Kaplan-Meier was used to assess the
      treatment duration and Cox regression estimated the hazard ratio (HR) of ceasing
      antidepressant therapy. RESULTS: There were 91,183 antidepressant users of which
      more than 50% were prevalent users. Among new users (n = 28,585), 50%
      discontinued within 6 months, and 61% within 12 months. The median duration for
      antidepressant treatment was 175 days [95% confidence interval (CI), 168-180].
      Patients who received psychological or psychiatrist care around the time of
      initiation had higher persistence (HR: 0.86, CI: 0.77-0.95 and HR: 0.67, CI: 0.61
      0.75 respectively), those with psychiatric disorders and dementia were also more
      persistent (HR: 0.82, CI: 0.77-0.88 and HR: 0.77, CI: 0.72-0.83 respectively). In
      contrast, patients with cancer and multi-morbidities had a higher risk of
      discontinuation (HR: 1.10, CI: 1.03-1.18 and HR: 1.16, CI: 1.05-1.28
      respectively). CONCLUSIONS: This analysis indicates persistence with
      antidepressants in the Australian veteran patients is inconsistent with clinical
      guidelines, with the majority of initiating patients provided with insufficient
      duration. Enhanced management of patients with characteristics associated with
      shorter persistence, including cancer and multi-morbidities, may improve
      antidepressant use.

PMID- 21713519
TI  - Preliminary studies for the development of a second generation
      granulocytapheresis (G-CAP) column. Part II: in vitro and ex vivo studies.
AB  - Our previous studies concluded Egyptian cotton was the most appropriate material
      for making a second generation granulocytapheresis (G-CAP) column as structural
      dimensions of the cotton fibers are able to attract granulocytes. Unfortunately,
      it is considered to be blood incompatible as its fibers are of non-synthetic
      origins. In this study we examined the alteration of the removal rates of blood
      cells with different surface modifications of Egyptian cotton to enhance its
      blood compatibility. The surface-modified cotton fibers were compared after three
      kinds of combination treatments. There were no differences in the removal rates
      of white blood cells (WBCs) and particularly neutrophils with the use of three
      kinds of biolized cottons. Next, an ex vivo animal study with a healthy dog was
      performed with the prototype of the G-CAP column. The dog's blood pressure (BP)
      decreased to approximately 80% of the initial values of BP at 20 min after the
      start of the extracorporeal circulation. The decrease in BP gradually reverted to
      normal. WBCs and particularly neutrophils decreased significantly at 15 min after
      the start of the extracorporeal circulation and remained low during the
      extracorporeal circulation. The ability of this column to remove WBCs was
      maintained during extracorporeal circulation. Especially, neutrophils at the
      inlet of the column were thoroughly removed for 1 h. Based upon these results, a
      second generation G-CAP column could be fabricated with Egyptian cotton and
      applied for clinical use on the condition that the biocompatibility of the
      Egyptian cotton needs to be improved by the appropriate biolization method.

PMID- 21713520
TI  - Significance of persistence of antibodies against Leishmania infantum in Sicilian
      patients affected by acute visceral leishmaniasis.
AB  - The background of this article is as follows: Few data are available about the
      persistence of serum-specific IgG antibodies to L. infantum after acute VL. The
      objective of this article is to evaluate the persistence of antibodies against L.
      infantum in patients healed from acute VL, and the kinetic of the same antibodies
      observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The
      methods which we used to obtain our objective are the following: 55 apparently
      immunocompetent, HIV-negative patients were examined for antibodies to L.
      infantum by IFAT over 14 years period, and we got the following results: Serum
      specific IgG antibodies titers decrease slowly, but constantly. In the patients
      with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an
      initial reduction, and a subsequent antibody levels rapidly increase, while in
      the patients with a clinical and parasitological diagnosis of VL not responding
      to specific therapy, we demonstrated persistent high level of antibodies to L.
      infantum. Finally, we conclude that specific antibodies to L. infantum might
      persist for many years, and decrease slowly, but steadily. The persistence of
      these specific antibodies is not related to poor therapeutic response or
      prognosis, but an acute increase in their levels might be a sentinel of a VL
      relapse, while persistence of high antibody levels could suggest a resistance to
      therapy.

PMID- 21713521
TI  - Distal radius fracture after Sauve-Kapandji procedure in a rheumatoid arthritis
      patient.
AB  - We report a case of distal radius fracture after a Sauve-Kapandji procedure
      combined with synovectomy and tendon transfer in a rheumatoid arthritis patient.
      This case shared several unusual features that were also seen in a previously
      reported case. Based on these features, we discuss favorable surgical treatment
      for the rheumatoid wrist with extensor tendon rupture, and also the optimal
      treatment for distal radius fracture after such procedures.

PMID- 21713522
TI  - Long-term outcomes, branch-specific expressivity, and disease-related mortality
      in von Hippel-Lindau type 2A.
AB  - Although a large kindred with familial pheochromocytoma (Pheo) and paraganglioma
      (PGL) was discovered in 1962 and later found to represent von Hippel-Lindau (VHL)
      type 2A (mutation Y112H), the phenotype lacks current characterization. Branch
      specific expressivity was suspected based on oral family history. Family pedigree
      analysis, prospective interviews, and extensive record review were used to extend
      the pedigree, determine phenotype, examine branch-specific expression, and
      analyze mortality rates over 5 decades. In its 3 known affected branches the
      kindred now comprises 107 people with or at-risk for VHL, of whom 49 have been
      diagnosed and 35/49 (71%) are clinically affected. Phenotypic cumulative lifetime
      risk was 71% for Pheo/PGL, 15% for hemangioblastoma, 33% for retinal angioma, 3%
      for renal cell carcinoma, and 3% for pancreatic cysts. The mean ages for VHL and
      Pheo/PGL diagnosis were younger in successive generations. Branch II-4
      predominately expressed RA, while branch II-5 predominantly expressed Pheo/PGL.
      Disease-specific mortality occurred early and was less frequent in successive
      generations. This analysis of Y112H VHL confirms a high cumulative risk for
      pheochromocytoma/paraganglioma. Over time, both age at diagnosis and disease
      specific mortality have decreased. The observed branch-specific expressivity
      prompts further study of genetic and environmental disease modifiers in this
      large family.

PMID- 21713523
TI  - Determinants of 40-year all-cause mortality in the European cohorts of the Seven
      Countries Study.
AB  - If a few risk factors had predictive power for all-cause mortality in different
      geographical-cultural areas, then preventive efforts might be concentrated on
      these. Thirteen potential risk factors were measured in 6,554 men aged 40-59
      around 1960 in Northern, Southern and Eastern European areas of the Seven
      Countries Study. In 40 years 85.3% of men died in the pooled areas (87.9, 81.8
      and 87.9% in Northern, Southern and Eastern Europe, respectively). Six risk
      factors were significant predictors of events in all three areas: directly for
      age, smoking habits, mean blood pressure, heart rate and ECG abnormalities;
      inversely for forced expiratory volume. In a pooled model also father and mother
      life status, socio-economic status, and arm circumference (the last one in an
      inverse way) had significant coefficients that were not heterogeneous across
      areas (except for socio-economic status). Serum cholesterol was around
      significance. ROC curves had values of 0.833, 0.806 and 0.819 respectively in
      Northern, Southern and Eastern Europe, and 0.827 in the pooled areas. Correlation
      coefficients between observed and expected cases in deciles of estimated risk
      were between 0.98 and 0.99. Survivors after 40 years in the lower half of the
      estimated risk were 10.7, 23.6 and 13.3% in Northern, Southern and Eastern
      Europe, respectively. Under- or over-estimate of cross-applying risk functions
      did not exceed 15%. All-cause mortality and survival in middle aged men during 40
      years were strongly associated with a few, mainly cardiovascular, risk factors,
      whose predictive power was similar in different cultures across Europe.

PMID- 21713525
TI  - Differential thermal performance curves in response to different habitats in the
      parasitoid Venturia canescens.
AB  - Environmental variability is expected to be important in shaping performance
      curves, reaction norms of phenotypic traits related to fitness. Models predict
      that the breadth of performance curves should increase with environmental
      variability at the expense of maximal performance. In this study, we compared the
      thermal performance curves of two sympatric populations of the parasitoid
      Venturia canescens that were observed under contrasting thermal regimes in their
      respective preferred habitats and differing in their modes of reproduction. Our
      results confirm the large effect of developmental temperature on phenotypic
      traits of insects and demonstrate that thelytokous and arrhenotokous wasps
      respond differently to temperature during development, in agreement with model
      predictions. For traits related to fecundity, thelytokous parasitoids, which
      usually occur in stable thermal conditions, exhibit specialist performance
      curves, maximising their reproductive success under a restricted range of
      temperature. In contrast, arrhenotokous parasitoids, which occur in variable
      climates, exhibit generalist performance curves, in keeping with the hypothesis
      "jack of all temperatures, master of none".

PMID- 21713524
TI  - Epidemiology of chronic kidney disease in children.
AB  - In the past 30 years there have been major improvements in the care of children
      with chronic kidney disease (CKD). However, most of the available epidemiological
      data stem from end-stage renal disease (ESRD) registries and information on the
      earlier stages of pediatric CKD is still limited. The median reported incidence
      of renal replacement therapy (RRT) in children aged 0-19 years across the world
      in 2008 was 9 (range: 4-18) [corrected] per million of the age-related
      population). [corrected] The prevalence of RRT in 2008 ranged from 18 to 100 per
      million of the age-related population. Congenital disorders, including congenital
      anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies,
      are responsible for about two thirds of all cases of CKD in developed countries,
      while acquired causes predominate in developing countries. Children with
      congenital disorders experience a slower progression of CKD than those with
      glomerulonephritis, resulting in a lower proportion of CAKUT in the ESRD
      population compared with less advanced stages of CKD. Most children with ESRD
      start on dialysis and then receive a transplant. While the survival rate of
      children with ERSD has improved, it remains about 30 times lower than that of
      healthy peers. Children now mainly die of cardiovascular causes and infection
      rather than from renal failure.

PMID- 21713526
TI  - Quantitative analysis and prediction of regional lymph node status in rectal
      cancer based on computed tomography imaging.
AB  - OBJECTIVES: To quantitatively evaluate regional lymph nodes in rectal cancer
      patients by using an automated, computer-aided approach, and to assess the
      accuracy of this approach in differentiating benign and malignant lymph nodes.
      METHODS: Patients (228) with newly diagnosed rectal cancer, confirmed by biopsy,
      underwent enhanced computed tomography (CT). Patients were assigned to the benign
      node or malignant node group according to histopathological analysis of node
      samples. All CT-detected lymph nodes were segmented using the edge detection
      method, and seven quantitative parameters of each node were measured. To increase
      the prediction accuracy, a hierarchical model combining the merits of the support
      and relevance vector machines was proposed to achieve higher performance.
      RESULTS: Of the 220 lymph nodes evaluated, 125 were positive and 95 were negative
      for metastases. Fractal dimension obtained by the Minkowski box-counting approach
      was higher in malignant nodes than in benign nodes, and there was a significant
      difference in heterogeneity between metastatic and non-metastatic lymph nodes.
      The overall performance of the proposed model is shown to have accuracy as high
      as 88% using morphological characterisation of lymph nodes. CONCLUSIONS: Computer
      aided quantitative analysis can improve the prediction of node status in rectal
      cancer.

PMID- 21713527
TI  - Endocrine-mediated effects of 4,4'-(hexafluoroisopropylidene)diphenol in SD rats,
      based on a subacute oral toxicity study.
AB  - The purpose of this study was to investigate the endocrine-mediated effects of
      4,4'-(hexafluoroisopropylidene)diphenol according to OECD test guideline no. 407.
      The estrogenic properties of this chemical have already been shown on
      uterotrophic assay, and this chemical is classified as a low-production volume
      chemical in REACH program. Rats were orally gavaged with 0, 10, 30, and 100
      mg/kg/day of test chemical for at least 28 days, beginning at 8 weeks of age. In
      the 100 mg/kg group of male rats, endocrine-mediated effects, atrophic changes in
      the mammary glands and testicular Leydig cells, decreased accessory sex organ
      weights, and hypertrophy of the adrenal zona fasciculata with increased organ
      weights were seen; there was dysfunction of the estrous cycle in the 30 and 100
      mg/kg groups, and increased serum T4 values were observed in the 100 mg/kg groups
      of both sexes. In addition, we also noted other findings, such as reduced body
      weight gains in the 30 and/or 100 mg/kg groups of both sexes, dilatation of the
      large intestinal lumen in the 100 mg/kg groups of both sexes, decreased
      hematopoiesis in the bone marrow and spleen, and decreased white blood cell
      counts in the 100 mg/kg group of male rats. Our results demonstrate that in a
      repeated-dose toxicity study, 4,4'-(hexafluoroisopropylidene)diphenol has various
      endocrine-mediated effects and its NOAEL (no observed adverse effect level) is 10
      mg/kg/day.

PMID- 21713528
TI  - Improvement of cardiac parameters in patients with acromegaly treated with
      medical therapies.
AB  - In acromegaly, growth hormone (GH) and insulin-like growth factor-1 (IGF-1)
      excess results in a specific cardiomyopathy characterized by concentric cardiac
      hypertrophy primarily associated with diastolic dysfunction that can lead to
      impaired systolic function and eventually heart failure. This review of the
      literature evaluates the effect of therapeutic intervention on cardiac
      parameters. Clinical studies investigating the impact of treatments for
      acromegaly on cardiac function published between January 1980 and January 2009
      were identified through electronic searches of Medline. Suppression of GH and IGF
      1 following surgery or medical treatment with somatostatin analogue therapy is
      effective in decreasing left ventricular (LV) hypertrophy, with subsequent
      improvement in cardiac function. First-line treatment with somatostatin analogues
      resulted in improved cardiac outcome compared with first-line surgery, possibly
      due to somatostatin analogues acting directly through somatostatin receptors on
      cardiac cells. Additional cardiac improvement has been reported when somatostatin
      analogue treatment was combined with surgery. In patients where complete
      biochemical control was not achieved, an improved cardiac performance following
      treatment with somatostatin analogues has been reported. Treatment with
      pegvisomant has been demonstrated to reduce LV hypertrophy and improve diastolic
      and systolic performance. In contrast, reports have suggested that treatment with
      the dopamine agonist cabergoline increased the incidence of valvular heart
      disease. Although surgery and somatostatin analogues are effective in improving
      cardiomyopathy, a greater beneficial effect is observed with somatostatin
      analogue treatment. Selected patients with acromegaly should consider first-line
      therapy or pre-treatment with somatostatin analogues prior to surgery to achieve
      biochemical control and improve cardiac dysfunction.

PMID- 21713529
TI  - Evaluation of left ventricular twist in acute myocardial infarction patients
      using speckle tracking imaging.
AB  - The aim of this study is to evaluate the differences of left ventricular (LV)
      twist and untwisting rate in patients with acute myocardial infarction (AMI) as
      compared with healthy subjects by means of Speckle Tracking Imaging (STI). 45 AMI
      patients (AMI group) and 48 healthy subjects (NOR group) were studied. Two
      dimensional STI was performed in all patients. Peak apical rotation, peak basal
      rotation, peak LV twist, peak basal untwisting rate, peak apical untwisting rate,
      peak LV untwisting rate, time to peak LV twist, and untwisting rate were
      measured. In comparison with the NOR group, peak LV rotational parameters were
      found to be decreased in the AMI group (P < 0.01). A strong correlation was found
      between the peak LV twist and LV ejection fraction in the overall study
      population (P < 0.001). The LV twist is strongly related to LV systolic function,
      and the impairment of LV function observed in patients with AMI is associated
      with a decrease of LV twist and untwist rate. The STI appears to accurately
      evaluate LV function.

PMID- 21713530
TI  - Generation and analysis of expressed sequence tags from a normalized cDNA library
      of young leaf from Ma bamboo (Dendrocalamus latiflorus Munro).
AB  - Ma bamboo (Dendrocalamus latiflorus Munro) belongs to Dendrocalamus genus,
      Bambusease tribe, Bambusoideae subfamily, Poaceae family. It is a representative
      species of clumping bamboo, and a principal commercial species for various
      construction purposes using mature culms and for human consumption using young
      shoots. A normalized cDNA library was constructed from young leaves of Ma bamboo
      and 9,574 high-quality ESTs were generated, from which 5,317 unigenes including
      1,502 contigs and 3,815 singletons were assembled. The unigenes were assigned
      into different gene ontology (GO) categories and summarized into 13 broad
      biologically functional groups according to similar functional characteristics or
      cellular roles by BLAST search against public databases. Eight hundred and ninety
      one unigenes were assigned by KO identifiers and mapped to six KEGG biochemical
      pathways. The transcripts involved in biosynthesis of secondary metabolites such
      as cytochrome 450, flavonol synthase/flavanone 3-hydroxylase, and dihydroflavonol
      4-reductase were well represented by 14 unigenes in the unigene set. The
      candidate genes involved in phytohormone metabolism, signal transduction and
      encoding cell wall-associated receptor kinases were also identified. Sixty-seven
      unigenes related to plant resistance (R) genes, including RPP genes, RGAs and
      RDL/RF genes, were discovered. These results will provide genome-wide knowledge
      about the molecular physiology of Ma bamboo young leaves and tools for advanced
      studies of molecular mechanism underlying leaf growth and development.

PMID- 21713531
TI  - Postdural puncture headache following acupuncture.

PMID- 21713532
TI  - Choroidal metastasis from chondrosarcoma.

PMID- 21713533
TI  - Primary transpupillary thermotherapy for small choroidal melanoma.
AB  - BACKGROUND: The treatment of small choroidal melanoma is controversial. Thermal
      laser-induced treatment is utilized by some centers but there is still sparse
      literature about the subject, mainly with short-term follow-up time. The efficacy
      of transpupillary thermotherapy (TTT) for the treatment of small choroidal
      melanomas was evaluated. METHODS: A prospective nonrandomized study of
      transpupillary thermotherapy for small (thickness <= 4.0 mm and basal diameter <=
      12 mm) pigmented choroidal melanomas presenting either growth or risk factors for
      growth and metastasis. Ophthalmoscopic aspect, tumor control, visual acuity and
      complications were evaluated. RESULTS: Twenty-seven patients were treated; mean
      age 61 years; mean tumor thickness before treatment was 2.7 mm and base was 8.52
      mm. After a mean of three treatment sessions and 45-month follow-up, mean tumor
      thickness decreased significantly to 1.34 mm (p < 0.001) and mean tumor base to
      5.48 mm (p < 0.001). Complications were observed in 12 patients (44%) and
      included retinal vascular occlusion, optic disc atrophy, retinal traction,
      vitreous hemorrhage, rhegmatogenous retinal detachment, and maculopathy. Lesions
      touching the optic disc were associated with a significantly higher rate of disc
      atrophy after treatment (60% vs. 40%, p=0.030). Visual acuity remained the same
      in nine eyes (33%), improved in five (19%) and decreased during the first 6
      months after treatment in 13 eyes (48%). Complete tumor control without
      recurrence was observed in 25 patients (93%). Recurrence at tumor margin was
      detected in two (7%). All eyes were preserved. One patient had tumor-related
      death. CONCLUSIONS: TTT is an effective treatment in the management of selected
      small choroidal melanoma. Decrease in visual acuity occurred early after
      treatment mainly associated with subfoveal and perifoveal tumors treatment and
      complications. Long-term randomized studies are still needed in order to better
      situate this treatment.

PMID- 21713534
TI  - How soft are biological helices? A measure of axial and lateral force constants
      in folate quadruplexes by high-pressure X-ray diffraction.
AB  - Alkaline folates self-associate in aqueous solutions to form columnar lyotropic
      phases. Such phases are made by quadruplexes, which are supramolecular helicoidal
      structures formed by a stacked array of folate tetramers. High-pressure
      synchrotron X-ray diffraction is used to analyze alkaline folate quadruplex
      stability and energetics. Diffraction data show that both inter-helical lateral
      and tetramer stacking distances decrease as a function of pressure. Lateral and
      axial quadruplex compressibilities and force constants have been derived and
      strong correlation between the strength of tetramer stacking and pressure effects
      demonstrated. In particular, quadruplex rigidity increases by changing Na+ to K+
      and by adding excess KCl, as a consequence of increased stacking interactions and
      quadruplex elongation.

PMID- 21713535
TI  - A molecular map of the apomixis-control locus in Paspalum procurrens and its
      comparative analysis with other species of Paspalum.
AB  - Since apomixis was first mapped in Paspalum, the absence of recombination that
      characterizes the related locus appeared to be the most difficult bottleneck to
      overcome for the dissection of the genetic determinants that control this trait.
      An approach to break the block of recombination was developed in this genus
      through an among-species comparative mapping strategy. A new apomictic species,
      P. procurrens (Q4094) was crossed with a sexual plant of P. simplex and their
      progeny was classified for reproductive mode with the aid of morphological,
      embryological and genetic analyses. On this progeny, a set of heterologous rice
      RFLP markers strictly co-segregating in coupling phase with apomixis was
      identified. These markers were all located on the telomeric region of the long
      arm of the chromosome 12 of rice. In spite of the lack of recombination exhibited
      by the apomixis-linked markers in P. procurrens, a comparative mapping analysis
      among P. simplex, P. malacophyllum, P. notatum and P. procurrens, allowed us to
      identify a small group of markers co-segregating with apomixis in all these
      species. These markers bracketed a chromosome region that likely contains all the
      genetic determinants of apomictic reproduction in Paspalum. The implications of
      this new inter-specific approach for overcoming the block of recombination to
      isolate the genetic determinants of apomixis and gain a better comprehension of
      genome structure of apomictic chromosome region are discussed.

PMID- 21713536
TI  - Targeted association analysis identified japonica rice varieties achieving
      Na(+)/K (+) homeostasis without the allelic make-up of the salt tolerant indica
      variety Nona Bokra.
AB  - During the last decade, a large number of QTLs and candidate genes for rice
      tolerance to salinity have been reported. Using 124 SNP and 52 SSR markers, we
      targeted 14 QTLs and 65 candidate genes for association mapping within the
      European Rice Core collection (ERCC) comprising 180 japonica accessions.
      Significant differences in phenotypic response to salinity were observed.
      Nineteen distinct loci significantly associated with one or more phenotypic
      response traits were detected. Linkage disequilibrium between these loci was
      extremely low, indicating a random distribution of favourable alleles in the
      ERCC. Analysis of the function of these loci indicated that all major tolerance
      mechanisms were present in the ERCC although the useful level of expression of
      the different mechanisms was scattered among different accessions. Under moderate
      salinity stress some accessions achieved the same level of control of Na(+)
      concentration and Na(+)/K(+) equilibrium as the indica reference variety for
      salinity tolerance Nona Bokra, although without sharing the same alleles at
      several loci associated with Na(+) concentration. This suggests (a) differences
      between indica and japonica subspecies in the effect of QTLs and genes involved
      in salinity tolerance and (b) further potential for the improvement of tolerance
      to salinity above the tolerance level of Nona Bokra, provided the underlying
      mechanisms are complementary at the whole plant level. No accession carried all
      favourable alleles, or showed the best phenotypic responses for all traits
      measured. At least nine accessions were needed to assemble the favourable alleles
      and all the best phenotypic responses. An effective strategy for the accumulation
      of the favourable alleles would be marker-assisted population improvement.

PMID- 21713537
TI  - [Is the training and continuing education for urologists in Germany still up to
      date?].
AB  - Besides its role in bladder and kidney cancer, urology plays a leading part in
      oncology particularly with regard to prostate cancer, the most frequent malignant
      tumor found in men. The multitude of hereditary anomalies of the urogenital tract
      and the resultant medical conditions, the importance of urinary tract infections
      including the still deadly urosepsis, urolithiasis which has become as widespread
      a condition as diabetes mellitus, and urinary incontinence as an increasing
      problem of a continuously aging population play such a large role in routine
      practice that every practicing physician must acquire the necessary skills for
      appropriate diagnosis and treatment. Is our current curriculum for training and
      continuing education adequate for this task?The primary goal of a meaningful
      program for continuing education must be to impart the corresponding qualities to
      young colleagues to ensure optimal patient care. The specialist certification
      exam itself should invariably be based nationwide on an objective written test:
      the existing European Board of Urology exam would be ideally suited to facilitate
      a comparison with other countries across Europe.

PMID- 21713538
TI  - Transcranial Doppler ultrasonography in acute ischemic stroke predicts stroke
      subtype and clinical outcome: a study in Omani population.
AB  - BACKGROUND: Transcranial Doppler ultrasonography (TCD) is being increasingly used
      for its ability to provide cerebral hemodynamic information in stroke. Few
      studies have explored its association with cerebral arteriographic changes and
      stroke subtype. This study explored the relation of TCD changes in acute stroke
      with stroke subtypes, MR cerebral arteriography and clinical outcome in Omani
      population. METHODS: Adult patients presenting with acute ischemic stroke within
      4 days of stroke onset were subjected to TCD through the temporal and
      suboccipital windows using a 2 MHz probe; flow velocities, pulsatility and
      direction of flow were recorded from arteries at the skull base. MR
      arteriographic (MRA) changes on corresponding arteries were graded on a scale of
      1-4. ANOVA, student's t test and ROC analysis were used to evaluate TCD in
      relation to stroke type, outcome and stenosis on MRA. RESULTS: Of 60 patients
      recruited, 52 (M:F::36:16; mean age: 60 + 13 years) had adequate bone window for
      TCD study. Large artery stroke occurred in 30 (58%) patients; lacunar stroke-11
      (21%); cardioembolic and mixed groups 9 (17%), other specificed causes-2 (4%).
      86.5% had evidence of intracranial disease. 10/52 patients (19%) died while 33
      (63%) had good outcome (modified Rankin Score 0-3). Of the 186 arteries studied
      by the two methods, 52 had TCD evidence of stenosis while 42 were abnormal on
      MRA, giving a sensitivity of 60%, specificity: 81.25%; positive likelihood ratio:
      3.18 and negative likelihood ratio: 0.5. 29/52 (56%) of patients had TCD changes
      in the arteries corresponding to stroke location. Abnormal TCD was associated
      with large artery strokes (p = 0.007), poor outcome (p = 0.038) and mortality (p
      = 0.01). CONCLUSION: This study of TCD in acute stroke in Omani population
      demonstrates a relatively higher burden of intracranial arterial disease. TCD
      changes are associated with type of stroke and outcome in this population. TCD is
      a simple and fairly useful method of evaluation in patients with acute stroke.
      Adopting TCD in evaluation of stroke patients may provide useful information
      regarding the pathophysiology which could enhance patient management.

PMID- 21713539
TI  - Evidence-based treatment of open ankle fractures.
AB  - Fractures of the ankle are fairly common injuries. Open ankle fractures are much
      less common and associated with severe injuries to surrounding tissues. We have
      performed a systematic review of the literature concerning the clinical results
      and complication rates in the treatment of open ankle fractures. We conducted a
      search limited to the following databases: Pubmed/Medline, Cochrane Database of
      Systematic Reviews, Cochrane Clinical Trial Register and Embase. These were
      searched from 1968 to April 2010 to identify studies relating to the treatment of
      open ankle fractures. Fifteen articles concerning 498 patients with treatment of
      an open ankle fracture were identified. The number of included patients varied
      from 11 to 64. There were 2 prospective and 13 retrospective studies. All
      articles were case series and classified as Level IV evidence. In 373 cases, open
      ankle fractures were treated by immediate internal fixation. In 125 cases, a
      conservative treatment or delayed/other fixation treatment was followed. Of those
      patients treated by immediate internal fixation, 81% had satisfactory result.
      Poor results (15%) were most commonly due to non-anatomic reductions, articular
      surface damage or deep infection. When conservative treatment was followed, 76%
      had satisfactory results. The most reported complications after immediate
      internal fixation were deep infection (8%) and skin necrosis (14%). There is a
      lack of high quality literature concerning the (operative) treatment of patients
      with open ankle fractures. Remarkable is that most authors reported satisfactory
      results after performance of their treatment protocol. Based on the available
      literature, we formulated guidelines regarding: timing of operative treatment,
      wound irrigation, the role of internal fixation, wound coverage and closure, the
      use of antibiotics and additional therapies.

PMID- 21713540
TI  - Is there an increased stem migration or compromised osteointegration of the Mayo
      short-stemmed prosthesis following cerclage wiring of an intrasurgical
      periprosthetic fracture?
AB  - AIM: Short-stemmed prostheses are increasingly regarded as implants of first
      choice in primary THA. As a result of the press-fit fixation in the femoral
      metaphysis, the occurrence of intraoperative fractures were reported. The aim of
      this study was to analyze the postoperative results of the Mayo short-stem
      prosthesis following treatment of an intrasurgical femur fracture with cerclage
      wiring. PATIENTS AND METHODS: From 1999 to 2005, in 38 patients (18 females, 20
      males; mean age 56 years; mean BMI = 27) with the diagnosis of coxarthrosis in
      whom a Mayo short-stemmed prosthesis has been implanted, an intraoperative
      fracture was observed. The fractures were treated with cerclage wiring (1
      cerclage, n = 32; 2 cerclages, n = 5; 3 cerclages, n = 1). Postoperatively, all
      patients were prescribed mobilization without weight-bearing (floor contact) on
      the treated leg for 6 weeks. Using the Wristing software, longitudinal stem
      migration and varus-valgus femoral stem alignment were examined digitally in
      anteroposterior X-rays taken immediately after surgery, after 6 weeks and on
      average after 5.7 years (Zeh et al., Z Orthop Unfall 149:200-205, 2011).
      Additionally, the incidence of periprosthetic radiolucent lines was captured in
      the anteroposterior X-rays and assigned to the Gruen zones. Additionally, a DEXA
      scan was performed. The X-rays of a matched control group after the implantation
      of a Mayo prosthesis without femur fracture were analyzed by the same method.
      RESULTS: There was no significant migration of the Mayo prosthesis in the study
      or control groups during postoperative follow-up (t test, P > 0.05). The cerclage
      group compared with the control group showed a statistically significant valgus
      tilt of 1.5 degrees  on average during the follow-up, which is regarded to be
      clinically not relevant. The frequency of occurrence of radiolucent lines was not
      statistically different (chi-square test, chi = 0.42, P = 0.51). DEXA scans
      showed no differences of the bone mineral density in the Gruen zones compared
      with a historical control group. CONCLUSION: After wiring of an intrasurgical
      fracture, no disadvantage could be proven for Mayo prosthesis regarding stem
      migration and varus-valgus alignment. Furthermore, due to the absence of
      differences in the occurrence of radiolucent lines and the same results in the
      DEXA scan, an unimpaired osseointegration is assumed.

PMID- 21713542
TI  - Determinants of spirometry use and accuracy of COPD diagnosis in primary care.
AB  - BACKGROUND: It is unclear if primary care physicians are following guidelines or
      using other patient characteristics and factors to determine when to perform
      spirometry in patients at risk for COPD. It is also unclear to what degree a
      diagnosis of COPD is accurately reflected by spirometry results. OBJECTIVES: To
      examine characteristics associated with use of spirometry in primary care for
      patients with increased risk for COPD and to determine the accuracy of COPD
      diagnosis in patients with spirometry. DESIGN: Retrospective cohort study.
      SUBJECTS: A cohort that met the following criteria was identified: >=35 years of
      age; >= 2 primary care visits in internal medicine clinic in 2007; at least one
      respiratory or smoking cessation medication, or diagnosis of COPD or shortness of
      breath or dyspnea in 2007. MAIN MEASURES: Medical records of all primary care
      physician visits prior to the time of inclusion in 2007 were reviewed. Data on
      patient demographics, co-morbidities, respiratory medication use, presence of
      symptoms, history of tobacco use, and pulmonary function tests were extracted.
      KEY RESULTS: A total 1052 patients were identified. Dyspnea on exertion (Adjusted
      odds ratio (AOR) 1.52 [95% CI 1.06-2.18]) and chronic cough (AOR 1.71 [1.07
      2.72]) were the only chronic symptoms associated with use of spirometry. Current
      (AOR 1.54 [0.99-2.40]) or past smoking (AOR 1.09 [0.72-1.65]) status were not
      associated with use of spirometry. Of the 159 patients with a diagnosis of COPD,
      93 (58.5%) met GOLD criteria and 81(50.9%) met lower limit of normal (LLN)
      criteria for COPD. CONCLUSION: Clinicians use spirometry more often among
      patients with symptoms suggestive of COPD but not more often among patients with
      current or past tobacco use. For patients who had a spirometry and a diagnosis of
      COPD, primary care physicians were accurate in their diagnosis only half of the
      time.

PMID- 21713543
TI  - The impact of cardiovascular disease prevalence on women's enrollment in landmark
      randomized cardiovascular trials: a systematic review.
AB  - Many studies have demonstrated that women are substantially underrepresented in
      cardiovascular trials, but few have considered that women develop cardiovascular
      disease at older ages than men. The extent to which observed gender enrollment
      inequalities persist after accounting for age-gender differences in disease
      prevalence is unknown. The purpose of the study was to compare observed rates of
      women participating in cardiovascular clinical trials with expected rates of
      female participation based on age- and gender-specific population disease
      prevalence. Publications between 1997 and 2009 in the three leading medical
      journals were included to calculate observed women's enrollment rates. Population
      based data in Canada were used to determine the expected enrollment rates of
      women. Multicenter, randomized cardiovascular clinical trials that enrolled both
      men and women were analyzed. Two reviewers independently extracted data on
      women's enrollment and important clinical trial characteristics. The female
      enrollment rate was 30% in the included 325 trials, which ranged from 27% in
      trials of coronary artery disease, 27% in heart failure, 31% in arrhythmia, to
      45% in primary prevention. Increased female enrollment correlated strongly with
      increasing age at recruitment in cardiovascular clinical trials (P < 0.001).
      After accounting for age- and gender-specific differences in disease prevalence,
      gaps in female enrollment were much lower than the expected enrollment rates
      estimated by 5% in coronary artery disease, 13% in heart failure, 9% in
      arrhythmia, and 3% in primary prevention. Only cardiovascular trials were
      evaluated in our study. Female underrepresentation in cardiovascular clinical
      trials is smaller than conventionally believed after accounting for age- and
      gender-specific population disease prevalence. Our findings suggest that greater
      representation of women in cardiovascular clinical trials can be achieved through
      the recruitment of older populations.

PMID- 21713544
TI  - The case against marketing genetic tests to primary care doctors to promote test
      ordering.

PMID- 21713545
TI  - Prevalence and densitometric characteristics of incomplete distal renal tubular
      acidosis in men with recurrent calcium nephrolithiasis.
AB  - The aim of this study was to assess the prevalence of incomplete distal renal
      tubular acidosis (idRTA) in men with recurrent calcium nephrolithiasis and its
      potential impact on bone mineral density. We conducted a retrospective analysis
      of 150 consecutive, male idiopathic recurrent calcium stone formers (RCSFs),
      which had originally been referred to the tertiary care stone center of the
      University Hospital of Berne for further metabolic evaluation. All RCSFs had been
      maintained on a free-choice diet while collecting two 24-h urine samples and
      delivered second morning urine samples after 12 h fasting. Among 12 RCSFs with a
      fasting urine pH >5.8, a modified 3-day ammonium chloride loading test identified
      idRTA in 10 patients (urine pH >5.32, idRTA group). We matched to each idRTA
      subject 5 control subjects from the 150 RCSFs, primary by BMI and then by age,
      i.e., 50 patients, without any acidification defect (non-RTA group) for
      comparative biochemistry and dual energy X-ray absorptiometry (DEXA) analyses.
      The prevalence of primary idRTA among RCSFs was 6.7% (10/150). Patients with
      idRTA had significantly higher 2-h fasting and 24-h urine pH (2-h urine pH: 6.6
      +/- 0.4 vs. 5.2 +/- 0.1, p = 0.001; 24-h urine pH: 6.1 +/- 0.2 vs. 5.3 +/- 0.3, p
      = 0.001), 24-h urinary calcium excretion (7.70 +/- 1.75 vs. 5.69 +/- 1.73 mmol/d,
      p = 0.02), but significantly lower 24-h urinary urea excretion (323 +/- 53 vs.
      399 +/- 114 mmol/d, p = 0.01), urinary citrate levels (2.32 +/- 0.82 vs. 3.01 +/-
      0.72 mmol/d, p = 0.04) and renal phosphate threshold normalized for the
      glomerular filtration rate (TmPO(4)/GFR: 0.66 +/- 0.17 vs. 0.82 +/- 0.21, p =
      0.03) compared to non-RTA patients. No significant difference in bone mineral
      density (BMD) was found between idRTA and non-RTA patients for the lumbar spine
      (LS BMD (g/cm(2)): 1.046 +/- 0.245 SD vs. 1.005 +/- 0.119 SD, p = 0.42) or
      femoral neck (FN BMD (g/cm(2)): 0.830 +/- 0.135 SD vs. 0.852 +/- 0.127 SD). Thus,
      idRTA occurs in 1 in 15 male RCSFs and should be sought in all recurrent calcium
      nephrolithiasis patients. Bone mineral density, however, does not appear to be
      significantly affected by idRTA.

PMID- 21713546
TI  - Stroke prevention: might vitamin D be safer than statins?

PMID- 21713547
TI  - A saddle nose with acute respiratory failure.

PMID- 21713548
TI  - An unusual case of dilated cardiomyopathy associated with partial
      hypopituitarism.

PMID- 21713549
TI  - PGS-FISH in reproductive medicine and perspective directions for improvement: a
      systematic review.
AB  - INTRODUCTION: Embryo selection can be carried out via morphological criteria or
      by using genetic studies based on Preimplantation Genetic Screening. In the
      present study, we evaluate the clinical validity of Preimplantation Genetic
      Screening with fluorescence in situ hybridization (PGS-FISH) compared with
      morphological embryo criteria. MATERIAL AND METHODS: A systematic review was made
      of the bibliography, with the following goals: firstly, to determine the
      prevalence of embryo chromosome alteration in clinical situations in which the
      PGS-FISH technique has been used; secondly, to calculate the statistics of
      diagnostic efficiency (negative Likelihood Ratio), using 2 * 2 tables, derived
      from PGS-FISH. The results obtained were compared with those obtained from embryo
      morphology. We calculated the probability of transferring at least one chromosome
      normal embryo when it was selected using either morphological criteria or PGS
      FISH, and considered what diagnostic performance should be expected of an embryo
      selection test with respect to achieving greater clinical validity than that
      obtained from embryo morphology. RESULTS: After an embryo morphology selection
      that produced a negative result (normal morphology), the likelihood of embryo
      aneuploidies was found to range from a pre-test value of 65% (prevalence of
      embryo chromosome alteration registered in all the study groups) to a post-test
      value of 55% (Confidence interval: 50-61), while after PGS-FISH with a negative
      result (euploid), the post-test probability was 42% (Confidence interval: 35-49)
      (p < 0.05). The probability of transferring at least one euploid embryo was the
      same whether 3 embryos were selected according to morphological criteria or
      whether 2, selected by PGS-FISH, were transferred. Any embryo selection test, if
      it is to provide greater clinical validity than embryo morphology, must present a
      LR-value of 0.40 (Confidence interval: 0.32-0.51) in single embryo transfer, and
      0.06 (CI: 0.05-0.07) in double embryo transfer. DISCUSSION: With currently
      available technology, and taking into account the number of embryos to be
      transferred, the clinical validity of PGS-FISH, although superior to that of
      morphological criteria, does not appear to be clinically relevant.

PMID- 21713550
TI  - CD44+/CD24- cells and lymph node metastasis in stage I and II invasive ductal
      carcinoma of the breast.
AB  - The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been
      reported as a possible cause of cancer metastasis and treatment failure.
      Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within
      the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was
      analyzed in 40 samples and in 10 lymph node metastases using flow cytometry
      phenotyping. Anti-human CD326 (EpCam; FITC), anti-human CD227 (MUC-1; FITC), anti
      human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4
      (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years
      (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The
      Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic
      regression was used for multivariate analysis. The median percentage of
      CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7%
      (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range,
      0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated
      with age, pT, tumor grade and HER2. We observed a significantly enrichment of
      CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with
      positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that
      metastatic dissemination is associated with an increase in tumor-initiating cells
      in stage I and II breast cancer.

PMID- 21713551
TI  - Effects of epidural TNF-alpha inhibitor injection: analysis of the pathological
      changes in a rat model of chronic compression of the dorsal root ganglion.
AB  - OBJECTIVES: To evaluate the efficacy of a single direct epidural injection of
      tumor necrosis factor (TNF)-alpha inhibitor to reduce the pathological changes in
      nerve fiber injuries in a rat model of chronic compression of the dorsal root
      ganglion (CCD). MATERIALS AND METHODS: A surgical procedure for CCD was performed
      in 17 adult male F-344 rats. The effects of the epidural TNF-alpha inhibitors on
      CCD-induced pathological changes were investigated. Three groups of rats (n = 17)
      were used: (1) CCD + saline (n = 4), (2) CCD + triamcinolone (n = 5), and (3) CCD
      + TNF-alpha inhibitors (n = 8). Their dorsal root ganglia and nerve roots were
      removed on postoperative day 14. The intraneural edema, demyelination, and
      Wallerian degeneration of all 17 rats were scored pathologically. RESULTS: The
      pathology scores of the rats in the TNF-alpha inhibitor treatment group (1.38 +/-
      0.74) indicated a mild degree of intraneural edema compared to the saline
      treatment group (2.25 +/- 0.50, p = 0.041). In addition, rats in the TNF-alpha
      inhibitor treatment group (2.13 +/- 0.35) had a mild degree of demyelination
      compared to the saline treatment group (2.75 +/- 0.50, p = 0.038) and the
      triamcinolone treatment group (2.80 +/- 0.45, p = 0.019). The differences in the
      pathology scores for Wallerian degeneration were not statistically significant in
      all three study groups (p = 0.658). CONCLUSION: The epidural injection of a TNF
      alpha inhibitor was more effective than a placebo and comparable to triamcinolone
      in reducing pathological nerve injury progression.

PMID- 21713552
TI  - Overview of migration, poverty and health dynamics in Nairobi City's slum
      settlements.
AB  - The Urbanization, Poverty, and Health Dynamics research program was designed to
      generate and provide the evidence base that would help governments, development
      partners, and other stakeholders understand how the urban slum context affects
      health outcomes in order to stimulate policy and action for uplifting the
      wellbeing of slum residents. The program was nested into the Nairobi Urban Health
      and Demographic Surveillance System, a uniquely rich longitudinal research
      platform, set up in Korogocho and Viwandani slum settlements in Nairobi city,
      Kenya. Findings provide rich insights on the context in which slum dwellers live
      and how poverty and migration status interacts with health issues over the life
      course. Contrary to popular opinions and beliefs that see slums as homogenous
      residential entities, the findings paint a picture of a highly dynamic and
      heterogeneous setting. While slum populations are highly mobile, about half of
      the population comprises relatively well doing long-term dwellers who have lived
      in slum settlements for over 10 years. The poor health outcomes that slum
      residents exhibit at all stages of the life course are rooted in three key
      characteristics of slum settlements: poor environmental conditions and
      infrastructure; limited access to services due to lack of income to pay for
      treatment and preventive services; and reliance on poor quality and mostly
      informal and unregulated health services that are not well suited to meeting the
      unique realities and health needs of slum dwellers. Consequently, policies and
      programs aimed at improving the wellbeing of slum dwellers should address
      comprehensively the underlying structural, economic, behavioral, and service
      oriented barriers to good health and productive lives among slum residents.

PMID- 21713553
TI  - Monitoring of health and demographic outcomes in poor urban settlements: evidence
      from the Nairobi Urban Health and Demographic Surveillance System.
AB  - The Nairobi Urban Health and Demographic Surveillance System (NUHDSS) was set up
      in Korogocho and Viwandani slum settlements to provide a platform for
      investigating linkages between urban poverty, health, and demographic and other
      socioeconomic outcomes, and to facilitate the evaluation of interventions to
      improve the wellbeing of the urban poor. Data from the NUHDSS confirm the high
      level of population mobility in slum settlements, and also demonstrate that slum
      settlements are long-term homes for many people. Research and intervention
      programs should take account of the duality of slum residency. Consistent with
      the trends observed countrywide, the data show substantial improvements in
      measures of child mortality, while there has been limited decline in fertility in
      slum settlements. The NUHDSS experience has shown that it is feasible to set up
      and implement long-term health and demographic surveillance system in urban slum
      settlements and to generate vital data for guiding policy and actions aimed at
      improving the wellbeing of the urban poor.

PMID- 21713554
TI  - Polymorphisms of the SCN1A gene in children and adolescents with primary headache
      and idiopathic or cryptogenic epilepsy: is there a linkage?
AB  - The purpose of this study was to evaluate the distribution of the polymorphisms
      of the SCN1A gene in a series of children and adolescents with primary headache
      and idiopathic or cryptogenic epilepsy compared to controls. Five non-synonymous
      exonic polymorphisms (1748A > T, 2656T > C, 3199A > G, 5771G > A, 5864T > C) of
      the SCN1A gene were selected and their genotyping was performed, by high
      resolution melting (HRM), in 49 cases and 100 controls. We found that among the
      five polymorphisms, only 3199A > G was a true polymorphism. We did not find a
      statistically significant difference between distribution of 3199A > G genotypes
      between cases and controls. We excluded the role of the SCN1A gene in the
      pathogenesis of comorbidity between headache (especially migraine) and epilepsy.
      The SCN1A gene is a major gene in different epilepsies and epilepsy syndromes;
      the HRM could be the new methodology, more rapid and efficacious, for molecular
      analysis of the SCN1A gene.

PMID- 21713556
TI  - Steroid treatment for patients with severe sepsis and septic shock.

PMID- 21713557
TI  - Analyzing lung crackle sounds: stethoscopes and beyond.

PMID- 21713558
TI  - Lung sound analysis correlates to injury and recruitment as identified by
      computed tomography: an experimental study.
AB  - PURPOSE: The aim of this study is to assess how analysis of the spectral
      characteristics of lung sounds can help in detecting lung injury and subsequent
      recruitment as verified by computed tomography (CT). METHODS: Lung sounds were
      recorded at four locations (ventral and dorsal on right and left side) in six
      ventilated pigs before and after unilateral oleic acid-induced lung injury during
      sequential increase of positive end-expiratory pressure (PEEP) from 0 to 20
      cmH(2)O. CT scans of the chest were used for comparison with lung aeration. Sound
      characteristics were compared by computer-aided analysis in the time and
      frequency domain as well as by clinicians. RESULTS: The presence of lung injury
      and its location were detected by substantial acoustic spectral components above
      500 Hz (frequency) and -70 dB (amplitude). Application of increasing PEEP
      gradually reduced the pathological components as CT analysis verified
      recruitment. At 20 cmH(2)O PEEP there was no further tidal recruitment of injured
      lung and the pathological sounds had disappeared, rendering the lung sounds of
      the injured lung similar to those of the control lung. This was mirrored by the
      clinicians' characterization of the sounds. CONCLUSIONS: Computer-aided analysis
      of lung sounds is suitable for detection of pathological lung sounds and may
      guide in detection and recruitment of poorly/nonaerated lung.

PMID- 21713560
TI  - Comment on Tusman et al.: Validation of Bohr dead space measured by volumetric
      capnography.

PMID- 21713561
TI  - Investigating the role of emotion during the search process in free recall.
AB  - Typically, research has shown that emotional words are remembered better than
      neutral words; however, most studies have reported only the mean proportion of
      correctly recalled words. The present study looked at various dependent measures
      used by search models to determine whether emotion can influence the search
      process as well. The results from Experiment 2 showed that when emotionality was
      made salient, participants were able to utilize emotional associations, in
      addition to temporal associations, to cue retrieval of additional emotional words
      during subsequent sampling but relied mainly on temporal context when the
      emotional information was not made salient (Experiment 1). Additionally, both
      experiments showed that emotional words were more likely to be output earlier in
      the recall sequence, which would suggest that emotion also serves to boost
      relative strength during initial sampling. Overall, the results suggest that
      emotion contributes to enhanced memory dynamically by influencing the probability
      of sampling an item during the search process--specifically, by boosting relative
      strength and strengthening interitem associations.

PMID- 21713562
TI  - Unitization, similarity, and overt attention in categorization and exposure.
AB  - Unitization, the creation of new stimulus features by the fusion of preexisting
      features, is one of the hypothesized processes of perceptual learning (Goldstone
      Annual Review of Psychology, 49:585-612, 1998). Some argue that unitization
      occurs to the extent that it is required for successful task performance (e.g.,
      Shiffrin & Lightfoot, 1997), while others argue that unitization is largely
      independent of functionality (e.g., McLaren & Mackintosh Animal Learning &
      Behavior, 30:177-200, 2000). Across three experiments, employing supervised
      category learning and unsupervised exposure, we investigated three predictions of
      the McLaren and Mackintosh (Animal Learning & Behavior, 30:177-200, 2000) model:
      (1) Unitization is accompanied by an initial increase in the subjective
      similarity of stimuli sharing a unitized component; (2) unitization of a
      configuration occurs through exposure to its components, even when the task does
      not require it; (3) as unitization approaches completion, salience of the
      unitized component may be reduced. Our data supported these predictions. We also
      found that unitization is associated with increases in overt attention to the
      unitized component, as measured through eye tracking.

PMID- 21713563
TI  - Therapeutic neovascularization for coronary disease: current state and future
      prospects.
AB  - Despite advances in surgical and percutaneous revascularization techniques,
      nearly one-third of patients with ischemic coronary artery disease are not
      candidates for revascularization due to suboptimal anatomy or receive suboptimal
      revascularization from these standard procedures. Neovascularization of the
      myocardium is not only a physiologic response to ischemia, but also potentially
      the target of new therapeutic strategies. Induced angiogenesis via protein, gene,
      and cell-based therapies showed initial promise in experiments using otherwise
      healthy laboratory animals. However, failure to translate these gains into humans
      prompted further study into the vascular environment and endothelial dysfunction.
      Understanding that factors such as hypertension, diabetes, and hyperlipidemia are
      not only placing patients at risk for coronary artery disease but also
      undermining our attempts in neovascularization therapies, has prompted us to
      rethink our therapeutic approach. Future directions for therapeutic
      neovascularization lie in therapies combining optimization of the vascular
      environment, improvement of endothelial function and other aspects of vascular
      formation and development.

PMID- 21713564
TI  - What we talk about when we talk about capacitance measured with the voltage-clamp
      step method.
AB  - Capacitance is a fundamental neuronal property. One common way to measure
      capacitance is to deliver a small voltage-clamp step that is long enough for the
      clamp current to come to steady state, and then to divide the integrated
      transient charge by the voltage-clamp step size. In an isopotential neuron, this
      method is known to measure the total cell capacitance. However, in a cell that is
      not isopotential, this measures only a fraction of the total capacitance. This
      has generally been thought of as measuring the capacitance of the "well-clamped"
      part of the membrane, but the exact meaning of this has been unclear. Here, we
      show that the capacitance measured in this way is a weighted sum of the total
      capacitance, where the weight for a given small patch of membrane is determined
      by the voltage deflection at that patch, as a fraction of the voltage-clamp step
      size. This quantifies precisely what it means to measure the capacitance of the
      "well-clamped" part of the neuron. Furthermore, it reveals that the voltage-clamp
      step method measures a well-defined quantity, one that may be more useful than
      the total cell capacitance for normalizing conductances measured in voltage-clamp
      in nonisopotential cells.

PMID- 21713565
TI  - Effects of a coumarin derivative, 4-methylumbelliferone, on seed germination and
      seedling establishment in Arabidopsis.
AB  - The root system is central for plant adaptation to soil heterogeneity and is
      organized primarily by root branching. To search for compounds that regulate root
      branching, a forward chemical genetics screen was employed, and 4
      methylumbelliferone (4-MU), a coumarin derivative, was found to be a potent
      regulator of lateral root formation. Exogenous application of 4-MU to Arabidopsis
      thaliana seeds affected germination and led to reduced primary root growth, the
      formation of bulbous root hairs, and irregular detached root caps accompanied by
      reorganization of the actin cytoskeleton in root tips before seedling
      establishment. Abundant lateral roots formed after exposure to 125 MUM 4-MU for
      22 days. Molecular, biochemical, and phytochemical approaches were used to
      determine the effect of 4-MU on root growth and root branching. Arabidopsis
      seedlings grown in the presence of 4-MU accumulated this compound only in roots,
      where it was partially transformed by UDP-glycosyltransferases (UGTs) into 4
      methylumbelliferyl-beta-D-glucoside (4-MU-Glc). The presence of 4-MU-Glc in
      seedling roots was consistent with the upregulation of several genes that encode
      UGTs in the roots. This shows that UGTs play an integral role in the
      detoxification of 4-MU in plants. The increased expression of two auxin efflux
      facilitator genes (PIN2 and PIN3) in response to 4-MU and the lack of response of
      the auxin receptor TIR1 and the key auxin biosynthetic gene YUCCA1 suggest that
      auxin redistribution, rather than auxin biosynthesis, may directly or indirectly
      mediate 4-MU-induced root branching.

PMID- 21713566
TI  - Are the phytoestrogens genistein and daidzein anti-herbivore defenses? A test
      using the gypsy moth (Lymantria dispar).
AB  - Phytoestrogens are compounds that have moderate estrogenic or anti-estrogenic
      activity toward mammals. Although genistein and daidzein, the main phytoestrogens
      of soybean, have been the subject of thousands of studies that address their
      benefit to human health, relatively little is known about their benefits to
      plants that produce them. It has been suggested that genistein and daidzein
      protect plants against arthropod herbivores, but direct tests of this hypothesis
      are rare. In this study, we evaluated the effect of genistein and daidzein on the
      survivorship, growth, and fecundity of the gypsy moth, a generalist insect
      herbivore that does not encounter phytoestrogens in its normal diet. We compared
      survivorship, egg-to-pupa growth rate, and 4th instar performance of gypsy moth
      caterpillars on artificial diets containing no phytoestrogen, genistein,
      daidzein, or a combination of genistein and daidzein. Our results indicate that
      genistein and daidzein do not decrease survivorship, growth, or fecundity of this
      insect herbivore. Therefore, it seems unlikely that the primary function of these
      compounds in aboveground plant tissues is anti-herbivore defense.

PMID- 21713567
TI  - Effects of dietary form of selenium on its distribution in eggs.
AB  - The objective of this experiment was to investigate the selenium distribution in
      eggs from hens fed diets supplemented with Se from sodium selenite (SS) or
      selenium-enriched yeast (SY). One-day-old female chickens of Hy-Line Brown breed
      were randomly divided into four groups according to dietary treatments and, for
      the subsequent 9 months, were fed diets which differed only in the form or amount
      of Se supplemented. During the whole experiment, group 1 (control) was fed basal
      diet (BD) with only background Se level of 0.13 mg/kg dry matter (DM). Diets for
      groups 2 and 3 consisted of BD supplemented with an Se dose of 0.4 mg/kg DM
      either in the form of SS or SY, respectively. Group 4 was fed BD supplemented
      with 0.9 mg Se/kg DM from SY. After 9 months of dietary treatments, the Se levels
      in egg yolk and albumen from hens fed unsupplemented diet were almost identical
      whereas eggs from hens given diet supplemented with SS showed significantly
      higher Se deposition in yolk than in albumen (P < 0.01). On the other hand, the
      feed supplementation with Se doses 0.4 or 0.9 mg/kg DM from SY resulted in
      significantly higher Se concentration in albumen than in yolk (both P < 0.001).
      The total Se amounts in whole eggs from hens in groups 1, 2, 3 and 4 were 5.1,
      14.4, 22.7 and 31.6 MUg Se/egg thus demonstrating the significantly higher (P <
      0.001) selenium deposition in eggs from hens given feed enriched with SY than
      from birds fed diet with equivalent SS dose. Regardless of dose and source, the
      selenium supplementation to feeds for groups 2, 3 and 4 resulted in significantly
      increased alpha-tocopherol concentration in egg yolk compared to control group 1
      (P < 0.001). The presented results demonstrate the different pattern of Se
      distribution in egg mass when laying hens are fed diets supplemented with
      inorganic or organic selenium sources.

PMID- 21713568
TI  - [Glaucoma in childhood : what should be considered?].

PMID- 21713569
TI  - Antifungal activity of some cyclooxygenase inhibitors on Candida albicans: PGE2
      dependent mechanism.

PMID- 21713570
TI  - Pullulan production by Aureobasidium pullulans cells immobilized in chitosan
      beads. Fungal pullulan production by immobilized cells.
AB  - Fungal cells of Aureobasidium pullulans ATCC 201253 were immobilized by
      entrapment in chitosan beads, and the immobilized cells were investigated for
      their ability to produce the polysaccharide pullulan using batch fermentation.
      The 1% chitosan-entrapped fungal cells were capable of producing pullulan for two
      cycles of 168 h using corn syrup as a carbon source. Pullulan production by the
      immobilized cells increased by 1.6-fold during the second production cycle (5.0
      g/l) relative to the first production cycle (3.1 g/l) with the difference in
      production being statistically significant after 168 h. The productivity of the
      immobilized cells increased during the second production cycle while its pullulan
      content decreased. The level of cell leakage from the support remained unchanged
      for both production cycles.

PMID- 21713571
TI  - Which is the last stage before packing in elective liver surgery?

PMID- 21713572
TI  - Re: Laparoscopic evaluation shows deficiencies in memory ring deployment during
      small ventral hernia repair.

PMID- 21713573
TI  - The necessity and reliability of intraoperative parathyroid hormone (PTH) testing
      in patients with mild hyperparathyroidism and PTH levels in the normal range.
AB  - BACKGROUND: Intraoperative parathyroid hormone (IoPTH) testing is useful in the
      management of hyperparathyroidism. The successful removal of hypersecreting
      parathyroids is indicated by a decrease in PTH levels >50% within 15 min. A
      subset of patients with mild hyperparathyroidism will actually have starting PTH
      levels in the normal range. We sought to determine if IoPTH testing is necessary
      in these patients and if the 50% rule delineating surgical cure is reliable.
      METHODS: A retrospective review was performed on all patients who underwent
      parathyroidectomy for hyperparathyroidism at a single institution from 3/2001 to
      8/2008. RESULTS: Of the 1,001 patients, 142 (14%) had mild hyperparathyroidism
      and normal baseline PTH levels (<65 pg/ml). Their mean PTH was 59 +/- 1 pg/ml.
      During surgery, 105 (74%) had a >50% decline in PTH levels after resection of
      hyperfunctioning parathyroid glands, and their operations were terminated. In
      contrast, 37 (26%) patients did not have a >50% decline in PTH levels leading to
      further surgical exploration. In these 37 patients, the PTH levels fell by >50%
      after the removal of the additional glands in 25 patients (17.6%) and dropped
      after 20 min in 7 patients (4.9%). In 5 patients (3.5%) the IoPTH did not drop.
      Of the 142 total patients, 91 had single adenomas and 51 patients had multi-gland
      disease. All patients (100%) were cured (normal serum calcium after 6 months).
      CONCLUSIONS: Intraoperative PTH testing plays an important role in the operative
      management in 14% of patients with mild hyperparathyroidism. Importantly, a 50%
      decline in IoPTH level within 15 min of parathyroidectomy is 96.5% reliable in
      predicting cure in these patients with PTH starting in the normal range.

PMID- 21713574
TI  - Planned hernia repair and late abdominal wall reconstruction.
AB  - Planned ventral hernia is a management strategy in which the abdominal fascial
      layer has been left unclosed and the viscera are covered only with original or
      grafted skin. Leaving the fascia open can be deliberate or unavoidable and most
      commonly results from staged repair of the abdominal wall due to trauma,
      peritonitis, pancreatitis, abdominal vascular emergencies, or abdominal
      compartment syndrome. The abdominal wall defects can be categorized as type I or
      II defects depending on whether there is intact, stable skin coverage. In defects
      with intact skin coverage, the most commonly used methods are the components
      separation technique and a prosthetic repair, sometimes used in combination. The
      advantages of the components separation technique is the ability to close the
      linea alba at the midline, creating a better functional result than a repair with
      inert mesh. Although the reherniation risk seems higher after components
      separation, the risk of infection is considerably lower. With a type II defect,
      with absent or unstable skin coverage, fascial repair alone is inadequate. Of the
      more complex reconstruction techniques, the use of a free tensor fasciae latae
      (TFL) flap utilizing a saphenous vein arteriovenous loop is the most promising.
      The advantages of the TFL flap include constant anatomy of the pedicle, a strong
      fascial layer, large-caliber vessels matching the size of the AV loop, and the
      ability to use large flaps (up to 20 * 35 cm). Whatever technique is used, the
      repair of complex abdominal wall defects requires close collaboration with
      plastic and abdominal surgeons, which is best managed in specialized centers.

PMID- 21713575
TI  - Safety and sterilization of mosquito net mesh for humanitarian inguinal
      hernioplasty.
AB  - BACKGROUND: Inguinal hernia repair is one of the most commonly performed
      operations in Africa. Prosthetic repair with commercially available mesh is
      generally considered too expensive in low-income countries. Elective groin hernia
      surgery with mosquito net mesh has recently been described. However, can mesh
      sterility in resource-poor countries be guaranteed to ensure both effectiveness
      and safety? METHODS: Copolymer and polyester mosquito net mesh were steam
      sterilized at varying temperatures. PubMed and EMBASE were searched using key
      words, MeSH, and subject headings (mosquito net mesh, mesh sterilization,
      inguinal hernia repair). RESULTS: Copolymer mosquito net mesh manufactured in
      India can be safely sterilized at lower (less "strict") temperatures (121 degrees
      C) than those usually demanded by advanced health care systems (134 degrees C).
      The literature search revealed a number of case series but all with limited
      follow-up. Available data, however, support the use of this type mosquito net
      mesh in the elective repair of hernias. CONCLUSIONS: Hernia repair with mosquito
      net mesh is a plausible, safe, cost-effective alternative in low-income
      countries. Sterilization in steam autoclaves that have accurate temperature
      control is required.

PMID- 21713576
TI  - Does gastric resection have a role in the management of severe postfundoplication
      gastric dysfunction?
AB  - BACKGROUND: Bloating, flatulence, early satiety, and dysphagia resolve in more
      than 90% of patients early after fundoplication. Gastric dysfunction can persist,
      however, and a small number of patients develop severe gastric dysfunction
      (gastroparesis). Management of gastroparesis after antireflux procedures is
      generally conservative, but gastroparesis can become refractory to medical
      therapy. The aim of this study was to assess the role of gastric resection in the
      management of the unusual patient with severe postfundoplication gastric
      dysfunction. METHODS: From January 1990 to October 2010, a total of 5,129 gastric
      resections were performed at our institution. From this cohort, we identified
      nine patients with postfundoplication gastric dysfunction managed with gastric
      resection. Clinical records were reviewed retrospectively for preoperative
      evaluation, perioperative course, and long-term outcomes. RESULTS: Over 20 years,
      nine patients were treated with gastric resection for debilitating gastric
      dysfunction after antireflux surgery. Seven of the nine patients were female; the
      median preoperative body mass index was 25 kg/m(2) (18-31 kg/m(2)). Median follow
      up was 23 months (1-97 months). Preoperatively, five patients required enteral
      feeding. Postoperatively, although there were no deaths, one patient required
      operative drainage of a subphrenic abscess, one developed temporary respiratory
      failure, and one was readmitted for partial small bowel obstruction. Six of the
      nine patients maintain their nutrition orally, but three are maintained with
      enteral nutrition. Only two patients are subjectively asymptomatic. CONCLUSIONS:
      Outcomes after gastric resection for postfundoplication gastric dysfunction are
      poor, with three of the nine patients requiring supplemental nutrition and seven
      of the nine having persistent symptoms.

PMID- 21713577
TI  - Prospective randomized trial of laparoscopic Nissen fundoplication with anterior
      versus posterior hiatal repair: late outcomes.
AB  - BACKGROUND: The technique used for hiatal closure in laparoscopic Nissen
      fundoplication might have an impact on the risk of postfundoplication dysphagia
      and hiatal herniation. In 1997, we commenced a randomized trial to evaluate the
      impact of anterior versus posterior hiatal repair techniques on these outcomes.
      In the present study, we evaluated the 10-year outcomes from this trial. METHODS:
      A total of 102 patients were randomized to undergo laparoscopic Nissen
      fundoplication with either anterior (47 patients) or posterior (55 patients)
      repair of the diaphragmatic hiatus. Outcomes were assessed using standardized
      clinical assessment scores that evaluated reflux symptoms, dysphagia, and
      satisfaction with the outcome following surgery. RESULTS: Clinical outcomes 10
      years after surgery were available for 93% of patients, and outcome scores were
      obtained for 43 patients in each group. Patients undergoing anterior hiatal
      repair were less likely to report dysphagia for lumpy solid foods (14.0% vs.
      39.5%, p = 0.01), although there were no significant differences in dysphagia
      outcomes for six other dysphagia assessment scores. There were no differences
      between the two groups for reflux symptoms, medication use, and overall
      satisfaction with the outcome of surgery. CONCLUSIONS: At the 10-year follow-up,
      the outcomes for the two groups were similar. Anterior hiatal repair is an
      acceptable technique for hiatal closure during laparoscopic Nissen
      fundoplication.

PMID- 21713578
TI  - Vascular constraints in laparoscopic renal allograft: comparative analysis of
      multiple and single renal arteries in 976 laparoscopic donor nephrectomies.
AB  - BACKGROUND: Since the initial description of laparoscopic donor nephrectomy (LDN)
      in 1995, the field of renal transplantation has continued to evolve. Although the
      identification of donor kidneys with multiple renal arteries (MRA) was considered
      a contraindication to LDN, improvement in the surgical technique to surmount the
      technical challenges of LDN with MRA have been established as the skill and
      laparoscopic experience of transplant surgeons evolves with time. Consensus
      regarding LDN with MRA and recipient outcomes is not uniformly documented amongst
      the transplant community. METHODS: A retrospective analysis of 976 patients who
      underwent LDN at our institution from January 1999 to August 2009 was performed.
      Patients were grouped based on the number of arteries and the data were compared
      with respect to patient demographics, operative characteristics, postoperative
      course and complications. RESULTS: The two donor groups had comparable outcomes
      except for operative time, which was significantly prolonged in patients with MRA
      kidneys when compared to a single renal artery (SRA) kidney (P < 0.01). 1-, 3
      year and estimated overall graft survival for the MRA recipient kidneys was
      significantly inferior when compared to SRA recipient kidneys. CONCLUSIONS: Our
      decade long experience with LDN demonstrates that operative times for MRA kidneys
      are longer than for SRA kidneys, however complication rates are similar.
      Laparoscopic donor nephrectomy with MRA is a safe and effective procedure for
      living kidney donation; however, the recipient graft outcomes with MRA kidneys
      warrant appropriate preoperative counseling of recipients.

PMID- 21713579
TI  - Popular belief meets surgical reality: impact of lunar phases, Friday the 13th
      and zodiac signs on emergency operations and intraoperative blood loss.
AB  - BACKGROUND: The influence of superstition, moon calendars, and popular belief on
      evidence-based medicine is stunning. More than 40% of medical staff is convinced
      that lunar phases can affect human behavior. The idea that Friday the 13th is
      associated with adverse events and bad luck is deep-rooted in the population of
      Western industrial countries. The aim of the present study was to test the
      hypothesis that these myths are transferable to real-life surgery. METHODS: We
      analyzed the extent to which moon phases, zodiac signs, and Friday the 13th
      influence blood loss, emergency frequency, and intestinal perforations by
      evaluating the operation records of all 27,914 consecutive patients of our
      institution undergoing general, visceral, or vascular surgery between August 2001
      and August 2010. Dates of surgery were allocated to lunar phases and to zodiac
      signs, as well as to Friday the 13th. RESULTS: A total of 111 lunar cycles and 15
      Fridays the 13th occurred within the 3,281-day observation period. Patients'
      characteristics did not differ in lunar phases, zodiac signs, or Fridays the
      13th. Full moon phases, the presence of Friday the 13th, and zodiac signs
      influenced neither intraoperative blood loss nor emergency frequency. No
      statistical peaks regarding perforated aortic aneurysms and gastrointestinal
      perforations were found on full moon or Friday the 13th. CONCLUSIONS: Scientific
      analysis of our data does not support the belief that moon phases, zodiac signs,
      or Friday 13th influence surgical blood loss and emergency frequency. Our data
      indicate that such beliefs are myths far beyond reality.

PMID- 21713580
TI  - The optimal surgical treatment for primary hyperparathyroidism in MEN1 patients:
      a systematic review.
AB  - BACKGROUND: The optimal surgical approach for patients with primary
      hyperparathyroidism (pHPT) and multiple endocrine neoplasia 1 (MEN1) is
      controversial. We sought to determine the optimal type of surgery for pHPT in
      MEN1. METHODS: We collected data on clinical presentation, surgery, and follow-up
      for MEN1 patients with pHPT at the University Medical Center Utrecht and
      affiliated hospitals between 1967 and 2008. Furthermore, we performed a
      systematic review of the literature and meta-analysis. Surgical procedures were
      classified into less than subtotal (<SPTX) versus subtotal (SPTX) and total
      parathyroidectomy (TPTX). RESULTS: Fifty-two patients underwent primary surgery
      for pHPT, of which 29 had <SPTX, 17 SPTX, and 6 TPTX. Recurrent pHPT was most
      frequent after SPTX (65%) followed by <SPTX (59%). Persistent disease was most
      frequent after <SPTX (31%). Time to recurrence was 61 months longer after SPTX
      than after <SPTX. Although recurrent pHPT was not seen after TPTX, permanent
      hypoparathyroidism developed in 67% of these patients. The meta-analysis showed
      that after SPTX and TPTX, patients had the lowest risk of persistent and
      recurrent pHPT. TPTX had the highest risk of permanent hypoparathyroidism. Large
      noncomparative studies showed a low recurrence rate after SPTX and TPTX.
      CONCLUSION: We believe that SPTX is the best surgical therapy for pHPT in MEN1.
      MEN1 patients with pHPT should not be treated with <SPTX because of the
      unacceptable high rate of recurrent and persistent pHPT. Additionally, a
      thymectomy should routinely be performed in these patients.

PMID- 21713581
TI  - [The 2-year follow-up results of a patient-specific interpositional knee
      implant].
AB  - BACKGROUND: Besides the primary goal of functional improvement and pain
      reduction, the operative treatment of unicompartmental arthritis in younger
      patients is focused on preservation of intact bone and joint structures. The
      question arises whether an interpositional knee implant based on magnetic
      resonance imaging (MRI) data can be an alternative treatment option to the
      established procedures of high tibial osteotomy and unicompartmental knee
      arthroplasty. METHODS: From June 2004 to May 2008 a total of 33 patients
      suffering from unicompartmental knee arthritis received a patient-specific
      interpositional implant (31 medial and 2 lateral) within a single arm trial. The
      mean follow-up time was 26.6 months (range 1-48 months) and the mean age of the
      patients was 54.5 years (range 39-65 years). In addition to the clinical results
      the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC)
      function scale and the Knee Society scores were measured. A descriptive data
      analysis, a variance analysis for repeated measurements and a determination of
      significance level were carried out. RESULTS: The 2-4 year results showed a
      significant improvement in the WOMAC function scale as well as the Knee Society
      scores. The knee function after 2 years was comparable to the preoperative
      situation with an extension to flexion of 0/2/130 degrees . The dislocation rate
      was 6% and the overall revision rate 21%. CONCLUSION: Despite acceptable
      functional results a significant pain relief, a complete preservation of bone and
      a lower rate of dislocations compared to the off-the-shelf Unispacer implant
      there were only limited indications for the customized interpositional knee
      implant with respect to the given contraindications due to the high 2 year
      revision rate.

PMID- 21713582
TI  - Technology, recommendation and design: on being a 'paternalistic' philosopher.
AB  - Philosophers have talked to each other about moral issues concerning technology,
      but few of them have talked about issues of technology and the good life, and
      even fewer have talked about technology and the good life with the public in the
      form of recommendation. In effect, recommendations for various technologies are
      often left to technologists and gurus. Given the potential benefits of informing
      the public on their impacts on the good life, however, this is a curious state of
      affairs. In the present paper, I will examine why philosophers are seemingly
      reluctant to offer recommendations to the public. While there are many reasons
      for philosophers to refrain from offering recommendations, I shall focus on a
      specific normative reason. More specifically, it appears that, according to a
      particular definition, offering recommendations can be viewed as paternalistic,
      and therefore is prima facie wrong to do so. I will provide an argument to show
      that the worry about paternalism is unfounded, because a form of paternalism
      engendered by technology is inevitable. Given the inevitability of paternalism, I
      note that philosophers should accept the duty to offer recommendations to the
      public. I will then briefly turn to design ethics, which has reconceptualised the
      role of philosophers and, in my mind, fitted well with the inevitability of
      paternalism. Finally, I shall argue that design ethics has to be supplemented by
      the practice of recommendation if it is to sustain its objective.

PMID- 21713583
TI  - [Structural and functional neuronal connectivity in Alzheimer's disease: a
      combined DTI and fMRI study].
AB  - BACKGROUND: Cognitive performance depends on intact cortical connectivity.
      Important for memory processing in the human brain is the connection between
      posterior cingulate cortex and hippocampus, directly as well as indirectly via
      the parahippocampal gyrus. These brain areas are involved early in Alzheimer's
      disease (AD). At the same time, they belong to the default mode network (DMN), a
      functional network showing high functional connectivity under resting state
      conditions. In AD, this connectivity in specifically compromised, offering the
      possibility to investigate the structural basis of functional brain connectivity.
      METHODS: We studied 18 patients with mild to moderate AD, 16 patients with mild
      cognitive impairment (MCI) and 20 healthy control subjects using diffusion tensor
      imaging (DTI) and resting state fMRI at 3.0 Tesla. We determined the effect of
      structural integrity in the posterior cingulate as assessed by DTI on the
      functional connectivity between posterior cingulate, hippocampus and
      parahippocampus during resting state in these three groups. RESULTS: Structural
      integrity was reduced in posterior cingulate fibre tracts in patients with AD in
      the left hemisphere; however, this effect was partly accounted for by age
      differences. All three groups showed high functional connectivity between
      posterior cingulate cortex and hippocampus, via both the direct and the indirect
      pathways. Determination of effective connectivity yielded a negative fractional
      anisotropy (FA)-moderated correlation on the direct pathway in AD and MCI for
      both hemispheres, and in healthy controls for the right hemisphere. The indirect
      pathway showed a negative FA-moderated correlation in AD for the right hemisphere
      and in MCI for both hemispheres. Healthy controls showed a positive correlation
      on the indirect pathway for the left hemisphere. CONCLUSION: Our data suggest
      that under healthy conditions, effective connectivity in the DMN between
      posterior cingulate cortex and hippocampus is mainly maintained by the indirect
      pathway via the parahippocampal gyrus. Patients with AD and patients with MCI
      show changes in this connectivity with a partial allocation to the direct
      pathway, most likely reflecting early parahippocampal lesions. The combination of
      DTI and fMRI broadens our understanding of human brain connectivity and its
      pathological changes with AD.

PMID- 21713584
TI  - Mouse models and type 2 diabetes: translational opportunities.
AB  - Type 2 diabetes prevalence is increasing worldwide. Treatments are available, but
      glycaemic control is not always effective in many patients. Better models are
      needed to create new and improved therapies and to expand our understanding of
      how type 2 diabetes begins and progresses. Translational research involves the
      transformation of knowledge from basic scientific discoveries to impacting on
      public health. This can allow identification of novel molecular mechanisms
      underlying the disease which can lead to preventative measures, biomarkers for
      diagnosis, or future therapies. Generation of genetically modified mice has
      allowed us to investigate the function of genes and develop reproducible models
      in which the phenotype of the animal can be tested. Mouse models have already
      given us insight into glucose metabolism and insulin secretion, identified novel
      pathways, and have been used to confirm genome-wide association studies. In this
      review we discuss the use of the mouse to clarify human genome-wide association
      study loci, understand genes and pathways involved in type 2 diabetes, and
      uncover novel targets for drug discovery.

PMID- 21713585
TI  - Advances in the treatment of chronic inflammatory demyelinating neuropathies in
      2010.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon disease
      of the peripheral nerves. The diagnosis is based mainly on clinical presentation,
      cerebrospinal fluid (CSF) examination, and electrodiagnostic studies. Treatment
      of CIDP has at least two components: supportive care and specific therapy
      including primarily steroids, intravenous immunoglobulins (IVIg), and
      plasmapheresis (PE). This review summarizes progress in the treatment of CIDP
      published during the last year.

PMID- 21713586
TI  - Reproductive tissue-specific expression profiling and genetic variation across a
      19 gene bovine beta-defensin cluster.
AB  - beta-defensins are small cationic peptides, with potent immunoregulatory and
      antimicrobial activity which are produced constitutively and inducibly by
      eukaryotic cells. This study profiles the expression of a cluster of 19 novel
      defensin genes which spans 320 kb on chromosome 13 in Bos taurus. It also
      assesses the genetic variation in these genes between two divergently selected
      cattle breeds. Using quantitative real-time PCR (qRT-PCR), all 19 genes in this
      cluster were shown to be expressed in the male genital tract and 9 in the female
      genital tract, in a region-specific manner. These genes were sequenced in
      Norwegian Red (NR) and Holstein-Friesian (HF) cattle for population genetic
      analysis. Of the 17 novel single nucleotide polymorphisms (SNPs) identified, 7
      were non-synonymous, 6 synonymous and 4 outside the protein coding region.
      Significant frequency differences in SNPs in bovine beta-defensins (BBD) 115,
      117, 121, and 122 were detected between the two breeds, which was also reflected
      at the haplotype level (P<0.05). There was clear segregation of the haplotypes
      into two blocks on chromosome 13 in both breeds, presumably due to historical
      recombination. This study documents genetic variation in this beta-defensin gene
      cluster between Norwegian Red and Holstein-Friesian cattle which may result from
      divergent selection for production and fertility traits in these two breeds.
      Regional expression in the epididymis and fallopian tube suggests a potential
      reproductive-immunobiology role for these genes in cattle.

PMID- 21713587
TI  - Laparoscopic-facilitated colonic endoscopic mucosal resection and endoscopic
      submucosal resection of adenomas: techniques to avoid segmental colectomy.

PMID- 21713589
TI  - Examining shared and unique aspects of Social Anxiety Disorder and Autism
      Spectrum Disorder using factor analysis.
AB  - Social Anxiety Disorder (SAD) and Autism Spectrum Disorders (ASD) are fairly
      common psychiatric conditions that impair the functioning of otherwise healthy
      young adults. Given that the two conditions frequently co-occur, measurement of
      the characteristics unique to each condition is critical. This study evaluated
      the structure and construct overlap of two screening measures of SAD and ASD.
      Results from 623 young adults indicated that separable, though highly correlated,
      factors can be derived from the two measures related to social anxiety and social
      difficulties. The ASD screening measure also taps unique factors related to
      restricted interests and attention to details, theory of mind deficits, and a
      preference for routine. Recommendations are provided for accurate screening of
      symptoms of both SAD and ASD.

PMID- 21713590
TI  - Is long-term prognosis for pervasive developmental disorder not otherwise
      specified different from prognosis for autistic disorder? Findings from a 30-year
      follow-up study.
AB  - We followed 74 children with autistic disorder (AD) and 39 children with
      pervasive developmental disorder not otherwise specified (PDD NOS) for 17-38
      years in a record linkage study. Rates of disability pension award, marital
      status, criminality and mortality were compared between groups. Disability
      pension award was the only outcome measure that differed significantly between
      the AD and PDD NOS groups (89% vs. 72%, p < 0.05). The lower rate of disability
      pension award in the PDD NOS group was predicted by better psychosocial
      functioning. The lack of substantial differences in prognosis between the groups
      supports a dimensional description of autism spectrum disorder, in line with
      proposed DSM-V revision.

PMID- 21713591
TI  - Distinct plasma profile of polar neutral amino acids, leucine, and glutamate in
      children with Autism Spectrum Disorders.
AB  - The goal of this investigation was to examine plasma amino acid (AA) levels in
      children with Autism Spectrum Disorders (ASD, N = 27) and neuro-typically
      developing controls (N = 20). We observed reduced plasma levels of most polar
      neutral AA and leucine in children with ASD. This AA profile conferred
      significant post hoc power for discriminating children with ASD from healthy
      children. Furthermore, statistical correlations suggested the lack of a typical
      decrease of glutamate and aspartate with age, and a non-typical increase of
      isoleucine and lysine with age in the ASD group. Findings from this limited
      prospective study warrant further examination of plasma AA levels in larger cross
      sectional and longitudinal cohorts to adequately assess for relationships with
      developmental and clinical features of ASD.

PMID- 21713592
TI  - Treatment of risk factors to prevent stroke.
AB  - Much of the decline in stroke incidence and mortality for the past several
      decades in Western countries has been attributed to better treatment of risk
      factors. Many epidemiological studies and clinical trials confirmed the
      importance of managing hypertension. Comparative trials of anti-hypertensive
      drugs or drug classes have not yielded clear results, but blood pressure
      variability may play an important role beyond the absolute value of blood
      pressure. Diabetes therapy remains a conundrum. Although diabetes is clearly a
      risk factor for ischemic stroke, treatment trials targeting different glycemic
      goals have not indicated that glucose lowering results in stroke prevention.
      Trials focused on insulin resistance are ongoing and they may be able to help
      establish the management of diabetes/impaired glucose tolerance. Evidence for
      treatment of dyslipidemia has contrasted science to diabetes mellitus.
      Dyslipidemia has not been strongly or consistently linked to ischemic stroke but
      the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)
      trial showed the impact of statin treatment in stroke prevention. The results of
      clinical trials investigating dabigatran and rivaroxaban clearly indicate
      alternative strategies to vitamin K antagonists in stroke prevention for persons
      with atrial fibrillation. Evidence for stroke prevention by life style
      modification, treating metabolic syndrome, sleep disordered breathing,
      lipoprotein (a), hyperhomocysteinemia, and coagulation disorders are also
      discussed.

PMID- 21713593
TI  - Comparison of two electromyographical endotracheal tube systems for
      intraoperative recurrent laryngeal nerve monitoring: reliability and side
      effects.
AB  - BACKGROUND: Recurrent laryngeal nerve (RLN) monitoring systems should be reliable
      and safe. Monitoring via electromyographical systems on an endotracheal tube
      (ETT) is widely spread. The MagStimTM system consists of an adhesive electrode to
      be fixed on an endotracheal tube. The XomedTM endotracheal tube provides
      integrated electrodes. Reliability and side effects had never been compared. As
      both systems have very different morphological properties, we hypothesized that
      there might be differences in reliability and the incidence of side effects.
      METHODS: In a retrospective quality management analysis of 118 patients
      (MagStimTM electrode, 57 patients; XomedTM ETT, 61 patients), we compared
      laryngeal side effects according to the Chilla score and detection rate of the
      RLN. RESULTS: Both systems had comparable detection rates of the RLN above 95%.
      Both electrode systems seemed to have similar reliability. Difficulties to detect
      the nerve were observed in seven patients (four with MagStim, three with Xomed).
      In the group with the XomedTM ETT, significantly less mild laryngeal side effects
      were observed. CONCLUSION: Both MagStimTM and XomedTM ETT were reliable in
      detecting the RLN. The XomedTM ETT, however, might cause milder laryngeal side
      effects compared with the MagStimTM electrode.

PMID- 21713594
TI  - Diagnostic evaluation, surgical technique, and perioperative management after
      esophagectomy: consensus statement of the German Advanced Surgical Treatment
      Study Group.
AB  - PURPOSE: Correct diagnosis, surgical treatment, and perioperative management of
      patients with esophageal carcinoma remain crucial for prognosis within multimodal
      treatment procedures. This study aims to achieve a consensus regarding current
      management strategies in esophageal cancer by questioning a panel of experts from
      the German Advanced Surgical Treatment Study (GAST) group, comprised of 9 centers
      specialized in esophageal surgery, with a combined total of >220 esophagectomies
      per year. MATERIALS AND METHODS: The Delphi method, a systematic and interactive,
      evidence-based approach, was used to obtain consensus statements from the GAST
      group regarding ambiguities and disparities in diagnosis, patient selection,
      surgical technique, and perioperative management of patients with esophageal
      carcinoma. After four rounds of surveys, agreement was measured by Likert scales
      and defined as full (100% agreement), near (>=66.6% agreement), or no consensus
      (<66.6% agreement). RESULTS: Full or near consensus was obtained for essential
      aspects of esophageal cancer staging, proper surgical technique, perioperative
      management and indication for primary surgery, and neoadjuvant treatment or
      palliative treatment. No consensus was achieved regarding acceptability of
      minimally invasive technique and postoperative nutrition after esophagectomy.
      CONCLUSION: The GAST consensus statement represents a position paper for
      treatment of patients with esophageal carcinoma which both contributes to the
      development of clinical treatment guidelines and outlines topics in need of
      further clinical studies.

PMID- 21713596
TI  - Cerebellar hemorrhage as a first presentation of acquired Hemophilia A.
AB  - BACKGROUND: Acquired hemophilia A (AHA) is an uncommon coagulation disorder
      caused by the development of autoantibodies against coagulation factor VIII
      (FVIII). While intracranial hemorrhage is a known complication of AHA,
      intracranial hemorrhage as the presenting manifestation of AHA has only been
      described in three previous case reports. METHOD: We report a case of an 86-year
      old woman with no previously reported history of coagulopathy presenting with an
      acute intraparenchymal cerebellar hemorrhage and laboratory studies demonstrating
      an isolated prolonged activated partial thromboplastin time (aPTT). We discuss an
      approach to the prolonged aPTT, and review the literature concerning the
      diagnosis and treatment of AHA. RESULTS: Occipital decompressive craniectomy with
      evacuation of the hemorrhage was performed. Eight hours following the procedure,
      the patient's status acutely declined with demonstration of a reoccurrence of the
      cerebellar hemorrhage and new right frontal lobe hemorrhage. After discussion
      with the patient's family, life-sustaining support measures were withdrawn.
      Postmortem analysis revealed a low FVIII activity level and the presence of FVIII
      inhibitor. CONCLUSION: The presentation of intracranial hemorrhage with an
      isolated prolonged aPTT is concerning for an acquired hemophilia with FVIII
      deficiency. Other causes of isolated prolonged aPTT such as a lupus anticoagulant
      must also be considered. Preoperative identification and work-up of the
      coagulation abnormality is essential to guide initial treatment.

PMID- 21713597
TI  - Application of triamcinolone acetonide paste to the endotracheal tube to reduce
      postoperative sore throat.

PMID- 21713598
TI  - Sickle cell anemia--molecular diagnosis and prenatal counseling: SGPGI
      experience.
AB  - OBJECTIVE: To study the issues and dilemmas in prenatal diagnosis of Sickle cell
      anemia (SCA) and to evaluate the role of genetic modifiers in counseling the
      families. METHODS: The authors studied the genotype in 47 individuals with
      increased HbS and three representative families were taken as an example for
      describing various issues which need to be sorted out for appropriate counseling.
      RESULTS: Of 47 individuals 24 were S beta thalassemia, 14 were homozygous sickle
      cell anemia (SS) and 9 were HbS trait. In the S beta thalassemia and homozygous
      SS cases, anemia was presenting manifestation in all. The transfusion requirement
      in these varied from 0-12 transfusions/ year. Hepatosplenomegaly was seen in 27
      cases (71%) and only splenomegaly in 9 cases (23.7%). Jaundice was observed in 34
      cases (84.2%). All the 47 subjects (including HbS trait) were studied by Hb
      Variant system and underwent DNA analysis for beta globin gene mutations, alpha
      globin gene number and XmnI polymorphism. One or two alpha gene deletion of 3.7
      kb (-alpha3.7/alphaalpha or -alpha3.7/-alpha3.7) was found in 11 out of 47 cases
      whereas alpha triplication was found in 2 cases. 28 cases were heterozygous (+/-)
      for XmnI polymorphism, 9 were homozygous negative (-/-) and 10 were homozygous
      positive (+/+). Patients with SCA co-inherited with alpha-thalassemia have less
      hemolysis as revealed by lower reticulocyte counts than with normal alpha
      genotype. The authors further discuss the issues and dilemmas faced during
      prenatal counseling of three families during this study. CONCLUSIONS: The
      knowledge of the relationship between genotype and phenotype, effect of the
      modifier genes has an important role in genetic counseling and for planning
      individualized treatment for sickle cell anemia.

PMID- 21713599
TI  - Intravenous diazepam, midazolam and lorazepam in acute seizure control.
AB  - OBJECTIVE: To evaluate the safety and efficacy of three benzodiazepine drugs:
      Lorazepam, Midazolam and Diazepam, when given parenterally in the control of
      acute seizure. METHODS: One hundred and twenty children of either sex in the age
      group 6 month to 14 years brought convulsing to the pediatric emergency services,
      were enrolled in the study. These were randomised to three equal groups of 40
      patients each; Group A-received diazepam, Group B-received midazolam, Group C
      received lorazepam. End of seizure episode (clinically) was defined as cessation
      of visible epileptic phenomenon or return of purposeful response to external
      stimuli within 15 min of drug administration. A stopwatch was used to measure
      various time intervals accurately. The patient's vitals were monitored and
      recorded in a predesigned performa. The primary outcome was the time to seizure
      cessation and secondary outcome was the side effects of the drugs. Data obtained
      was analysed statistically using student's t-test and chi-square test. RESULTS:
      Mean duration to clinical seizure cessation was comparable among the three
      groups. For diazepam group it was 84.94 +/- 38.56 s, for midazolam group it was
      92.69 +/- 25.97 s, for lorazepam group it was 91.12 +/- 23.58 s. Number of
      patients with any abnormality in seizure cessation were significantly higher in
      diazepam group [11/40 (27.5%)] when compared to the midazolam [4/40 (10%)] and
      lorazepam group [2/40 (5%)]. Number of patients requiring 2nd dose to control
      seizures was significantly higher [4/40 (10%)] in diazepam group when compared to
      lorazepam group [0/40 (0%)] but diazepam and midazolam and midazolam and
      lorazepam were comparable in this aspect.All the three drugs were comparable in
      terms of side effects except excessive somnolence which was significantly higher
      in diazepam group. CONCLUSIONS: All the three groups were comparable in terms of
      time to clinical seizure cessation, seizure recurrence and uncontrolled seizures
      after drug administration. However, number of patients requiring second dose to
      control seizures were significantly higher in diazepam group when compared to
      lorazepam group. Excessive somnolence and sedation occurred more frequently with
      diazepam.

PMID- 21713600
TI  - Silencing Poly (ADP-Ribose) glycohydrolase (PARG) expression inhibits growth of
      human colon cancer cells in vitro via PI3K/Akt/NFkappa-B pathway.
AB  - Poly ADP-ribose polymerase (PARP) which is closely related to Poly ADP-ribose
      glycohydrolase (PARG) has already been thoroughly investigated in both
      experimental and clinical cancer trials compared to the latter. Nevertheless, in
      this experiment the importance of PARG expression was highlighted; whereby it is
      being silenced via lentivirus vector-mediated short hairpin RNA (shRNA). MTT
      assay showed that there was an inhibition in human Lovo colon cancer cell growth
      and flow cytometry demonstrated an increase in the population of cells in
      G(0)/G(1) phase with a decrease in the S phase in transfected Lovo cells.
      Furthermore, our results suggested that the effect of silencing PARG leads to the
      inhibition of PARP expression; related to a decrease in the expression of Nuclear
      Factor Kappa-B (NFkappa-B) with an increase in Akt(473) phosphorylation;
      suggesting that the Phosphoinositol 3-kinase (PI3K)/Akt/NFkappa-B pathway is
      important for cellular growth and proliferation. Hence, this study emphasizes and
      converges on the relevance of silencing PARG which inhibits growth of human
      colonic cancer cells via PI3K/Akt/NFkappa-B pathway; as colon carcinoma remains
      to be amongst one of the commonest cancers throughout the world with high
      morbidity and mortality rates.

PMID- 21713601
TI  - Chemotherapy response analysis for osteosarcom with intra-arterial chemotherapy
      by subcutaneous implantable delivery system.
AB  - To summarize the experience in intraarterial neoadjuvant chemotherapy for
      extremity osteosarcoma. Between January 2002 and December 2007,111 patients with
      stage IIB extremity osteosarcoma received preoperative intraarterial therapy with
      subcutaneous implantation of chemotherapy pump as well as en bloc resection, and
      postoperative adjuvant chemotherapy. There were 63 males and 48 females with an
      average age of 18 (range, 14 ~ 39 years). The time from symptom onset to
      hospitalization varied from several days to 6 months. The induction chemotherapy
      regimen includes: epirubicin [50 ~ 70 mg/m(2) by 4-hour intraarterial
      infusion/day for 3 day] and cisplatin [100 ~ 120 mg/m(2) by 2-hour intraarterial
      infusion/day for 3 days] repetitively every 2 ~ 3 weeks. Among which 24 cases
      only received two cycles induction chemotherapy was set to nonstandard
      chemotherapy group and 87 cases received three to six cycles induction
      chemotherapy set to standard chemotherapy group. The number of preoperative
      chemotherapy-cycles of standard chemotherapy group depends on the clinical and
      radiographic evaluation of chemotherapy efficacy. Median follow-up time was 28(8
      ~ 48) months. The rate of limb preservation surgery was 89.53% (77/86) in
      standard chemotherapy group,and was 37.5% (9/24) in nonstandard chemotherapy
      group. Kaplan-Meier survival analysis showed that the 3-year overall survival
      rate and disease free survival rate of all the 111 cases were 68.3% and 65.9%
      respectively. There were significant differences in overall survival rate (38.9%,
      80.0%, P = 0.000), disease free survival rate (30.1%, 79.5%, P = 0.000), distant
      metastasis rate (66.67%, 16.09%, P = 0.0000) and local recurrence rate (58.33%,
      13.79%, P = 0.0000) between nonstandard chemotherapy group and standard
      chemotherapy group. Standard intraarterial neo-adjuvant chemotherapy was more
      effective than nonstandard intraarterial induction chemotherapy to stage IIB
      extremity osteosarcoma.

PMID- 21713602
TI  - From "Periodical Observations" to "Anthochronology" and "Phenology" - the
      scientific debate between Adolphe Quetelet and Charles Morren on the origin of
      the word "Phenology".
AB  - Mankind has observed and documented life cycle stages of plants and animals for a
      long time. However, it was comparatively recently that the newly emerging science
      was given its name. The name of Charles Morren and the year 1853 are being cited,
      although not frequently. Exact information is hardly known among present-day
      phenologists, yet new evidence shows that the term "phenology" was already in use
      in 1849. In the early 1840s, physicist and astronomer Adolphe Quetelet set up an
      observational network named "Observations of periodical Phenomena of the Animal
      and Vegetable Kingdom" and issued instructions for it. Even though biologist
      Charles Morren welcomed Quetelet's initiative, differences between Morren and
      Quentlet regarding the instructions for the observations and the potential
      results soon arose and a debate started, which lasted for nearly 10 years. In the
      wake of these disagreements, Morren was compelled to create a new term to denote
      his ideas on "periodical phenomena". At first, he temporally used the word
      anthochronology, but in the end he coined the word phenology. The term was first
      used in a public lecture at the Academie royale des Sciences, des Lettres et des
      Beaux-Arts de Belgique' in Brussels on 16 December 1849, and simultaneously in
      the December 1849 issue of volume V of the Annales de la Societe royale
      d'Agriculture et de Botanique de Gand. One had to wait until 1853 before the new
      name appeared in the title of one of Morren's publications. Based on evidence
      from archives and original publications, we trace the 10-year-long scientific
      debate between Morren and Quetelet. Morren states his biologist's view on the
      subject and extends the more climate-related definition of Quetelet of
      "periodical phenomena".

PMID- 21713603
TI  - Patterns of recurrence and outcome in patients with surgically resected small
      cell lung cancer.
AB  - BACKGROUND: Although prophylactic cranial irradiation (PCI) in limited-stage (LS)
      small cell lung cancer (SCLC) patients who are surgically resected and treated
      with adjuvant chemotherapy is considered to be a reasonable treatment option, the
      efficacy of PCI for those patients remains unclear. METHODS: The records of 28
      patients with SCLC undergoing curative surgery at the Aichi Cancer Center
      Hospital between 1995 and March 2008 were retrospectively reviewed to assess
      patterns of relapse and overall survival. RESULTS: The patients were 27 men and 1
      woman. Eight patients underwent induction chemotherapy. Fourteen patients (50%)
      had pathologic stage (p-stage) I disease, 7 patients (25%) had p-stage II, and 7
      patients (25%) had p-stage III. Nineteen patients underwent adjuvant chemotherapy
      and one patient received adjuvant chemoradiotherapy. There were a total of 13
      deaths and 8 were disease-related. Most patients developed hematogenous distant
      metastases before their death. The 5-year overall probability of survival was
      47%. Ten (36%) of the 28 patients had a relapse. Two had a local relapse alone,
      one patient had combined local and distant relapses, and seven patients had
      distant metastases alone as their first site of failure. Four patients with p
      stage II/III disease developed brain metastases with a cumulative incidence at 1
      and 2 years of 25 and 36%, respectively. CONCLUSIONS: Our retrospective study
      suggested that PCI might have a role in surgically resected patients with p-stage
      II/III SCLC because of their relatively high frequency of brain metastasis.

PMID- 21713604
TI  - Therapeutic use of microRNAs in myocardial diseases.
AB  - The discovery of regulatory non-coding (nc) RNAs has opened a new world in cell
      biology. Within this class of ncRNAs, microRNAs (miRNAs) have been found to be
      involved in many cellular functions. Regarding the cardiovascular system, miRNAs
      regulate cardiomyocyte size and survival, the action potential, angiogenesis,
      mitochondrial function, and energetics. Moreover, misexpression of miRNAs has
      been linked to pathology, and altered levels of certain miRNAs even may cause
      disease. Thus, the manipulation of miRNAs, by affecting the biological processes
      in which they are implicated, may be used to improve cardiac function. The
      expression of microRNAs can be modulated through different approaches. This
      article reviews these issues in relation to the therapeutic potential of miRNAs
      for heart failure.

PMID- 21713605
TI  - A direct comparison of the behavioral and physiological effects of
      methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans.
AB  - RATIONALE: Despite their chemical similarities, methamphetamine and 3,4
      methylenedioxymethamphetamine (MDMA) produce differing neurochemical and
      behavioral responses in animals. In humans, individual studies of methamphetamine
      and MDMA indicate that the drugs engender overlapping and divergent effects;
      there are only limited data comparing the two drugs in the same individuals.
      OBJECTIVES: This study examined the effects of methamphetamine and MDMA using a
      within-subject design. METHODS: Eleven adult volunteers completed this 13-day
      residential laboratory study, which consisted of four 3-day blocks of sessions.
      On the first day of each block, participants received oral methamphetamine (20,
      40 mg), MDMA (100 mg), or placebo. Drug plasma concentrations, cardiovascular,
      subjective, and cognitive/psychomotor performance effects were assessed before
      drug administration and after. Food intake and sleep were also assessed. On
      subsequent days of each block, placebo was administered and residual effects were
      assessed. RESULTS: Acutely, both drugs increased cardiovascular measures and
      "positive" subjective effects and decreased food intake. In addition, when asked
      to identify each drug, participants had difficulty distinguishing between the
      amphetamines. The drugs also produced divergent effects: methamphetamine improved
      performance and disrupted sleep, while MDMA increased "negative" subjective
      effect ratings. Few residual drug effects were noted for either drug.
      CONCLUSIONS: It is possible that the differences observed could explain the
      differential public perception and abuse potential associated with these
      amphetamines. Alternatively, the route of administration by which the drugs are
      used recreationally might account for the many of the effects attributed to these
      drugs (i.e., MDMA is primarily used orally, whereas methamphetamine is used by
      routes associated with higher abuse potential).

PMID- 21713607
TI  - [Acute liver failure. How much diagnostic work-up and therapy does my patient
      need?].
AB  - Acute liver failure is a multisystem disease with predominantly sudden and severe
      hepatic injury and hepatic encephalopathy caused by apoptotic or necrotic
      hepatocyte damage. The clinical challenge in patients with acute liver failure is
      to promptly identify those with poor prognosis and refer them for emergency liver
      transplantation. This review article highlights the main aspects of decision
      making in the setting of acute liver failure, summarizes new aspects of its
      critical care management and gives an overview of sclerosing cholangitis in the
      critically ill patient, an under-recognized disease entity that can progress to
      acute liver failure.

PMID- 21713611
TI  - [New agents for the therapy of angina pectoris].
AB  - There is a renaissance of medical treatment of chronic angina pectoris despite of
      advances in interventional therapy. New drugs include nicorandil, ivabradine and
      ranolazine. Nicorandil dilates venous and arterial vessels via relaxation of
      smooth muscle cells. Since the drug has only recently been approved, the German
      experience is limited. Ivabradine exerts an anti-anginous effect by selective
      action on the sinus node with reduction of heart rate. Multiple studies have
      demonstrated its anti-anginal efficacy, which has also been shown if it was used
      as an additional therapy to classic anti-anginal treatment. Its use is reasonable
      as a substitute for beta-blockers or as an "add-on therapy" combined with beta
      blockers, if the target heart rate for treatment of angina pectoris has not been
      reached. Ranolazine delays the late sodium current into the myocytes. Thereby, it
      improves the diastolic ventricular function and the microcirculation of the
      myocardium. Several large studies confirmed the anti-anginal efficacy of the
      drug. Currently it is used if angina pectoris still occurs under a combined
      treatment with different classic anti-anginal drugs.

PMID- 21713627
TI  - Strategies for boosting the accumulation of correctly folded recombinant proteins
      expressed in Escherichia coli.
AB  - The yields of soluble recombinant protein expressed in bacteria can be
      significantly enhanced by optimally exploiting the cell-folding machinery. The
      proposed protocol describes the strategies that can be used to reach a suitable
      ratio between heat-shock proteins and target proteins. Specifically, molecular
      recombinant chaperones can be overexpressed or cell-native chaperones are
      stimulated by inducing chemical and physical stress. Furthermore, the protein
      synthesis block can make available the cell-folding machinery for in vivo,
      disaggregating and refolding the already produced misfolded recombinant target
      protein. A rapid fluorimetric analytical method allows the evaluation of the
      protein monodispersity at any single purification step and enables comparison of
      different growth combinations that are useful to test for screening the optimal
      conditions for each recombinant protein.

PMID- 21713628
TI  - An Escherichia coli cell-free system for recombinant protein synthesis on a
      milligram scale.
AB  - In vitro translation systems derived from a wide range of organisms have been
      described in the literature and are widely used in biomedical research
      laboratories. Perhaps the most robust and efficient of these cell-free systems is
      that derived from Escherichia coli. Over the past decade or so, experimental
      strategies have been developed which have enhanced the efficiency and stability
      of E. coli cell-free systems such that we can now prepare recombinant proteins on
      a scale suitable for purification and analysis by biophysical and structural
      biology techniques, which commonly require relatively large quantities of
      protein. This chapter describes in detail the protocols employed in our
      laboratory to prepare translationally active E. coli extracts and to synthesise
      proteins on a milligram scale from these extracts.

PMID- 21713629
TI  - Synthesis of peptide sequences derived from fibril-forming proteins.
AB  - The pathogenesis of a large number of diseases, including Alzheimer's Disease,
      Parkinson's Disease, and Creutzfeldt-Jakob Disease (CJD), is associated with
      protein aggregation and the formation of amyloid, fibrillar deposits. Peptide
      fragments of amyloid-forming proteins have been found to form fibrils in their
      own right and have become important tools for unlocking the mechanism of amyloid
      fibril formation and the pathogenesis of amyloid diseases. The synthesis and
      purification of peptide sequences derived from amyloid fibril-forming proteins
      can be extremely challenging. The synthesis may not proceed well, generating a
      very low quality crude product which can be difficult to purify. Even clean crude
      peptides can be difficult to purify, as they are often insoluble or form fibrils
      rapidly in solution. This chapter presents methods to recognise and to overcome
      the difficulties associated with the synthesis, and purification of fibril
      forming peptides, illustrating the points with three synthetic examples.

PMID- 21713630
TI  - Refolding your protein with a little help from REFOLD.
AB  - The expression and harvesting of proteins from insoluble inclusion bodies by
      solubilization and refolding is a technique commonly used in the production of
      recombinant proteins. Despite the importance of refolding, publications in the
      literature are essentially ad hoc reports consisting of a dazzling array of
      experimental protocols and a diverse collection of buffer cocktails. For the
      protein scientists, using this information to refold their protein of interest
      presents enormous challenges. Here, we describe some of the practical
      considerations in refolding and present several standard protocols. Further, we
      describe how refolding procedures can be designed and modified using the
      information in the REFOLD database (http://refold.med.monash.edu.au), a freely
      available, open repository for protocols describing the refolding and
      purification of recombinant proteins.

PMID- 21713631
TI  - Circular dichroism and its use in protein-folding studies.
AB  - The way in which proteins fold into the complex 3 dimensional structures that are
      responsible for their function is a subject of great practical as well as
      fundamental significance because of the involvement of folding and misfolding in
      a number of serious human and animal diseases. Ultraviolet circular dichroism
      (CD) reports on the secondary and tertiary structure of proteins. Measurements
      can be made on proteins in the solution phase, and critically time-resolved
      measurements can be made with millisecond resolution. This combination of
      characteristics makes CD a useful tool for investigating protein folding, and
      indeed any process involving changes in protein structure. Experimental methods
      for a typical time-resolved CD experiment are described, and some common problems
      identified.

PMID- 21713632
TI  - Distance measurements by continuous wave EPR spectroscopy to monitor protein
      folding.
AB  - Site-Directed Spin Labeling Electron Paramagnetic Resonance (SDSL-EPR) offers a
      powerful method for the structural analysis of protein folds. This method can be
      used to test and build secondary, tertiary, and quaternary structural models as
      well as measure protein conformational changes in solution. Insertion of two
      cysteine residues into the protein backbone using molecular biology methods and
      the subsequent labeling of the cysteine residues with a paramagnetic spin label
      enables the technique of EPR to be used as a molecular spectroscopic ruler. EPR
      measures the dipolar interaction between pairs of paramagnetic spin labels to
      yield internitroxide distances from which quantitative structural information on
      a protein fold can then be obtained. Interspin dipolar interaction between two
      spin labels at less than 25  A are measured using continuous wave (CW) EPR
      methods. As for any low-resolution distance methods, the positioning of the spin
      labels and the number of distance constraints to be measured are dependent on the
      structural question being asked, thus a pattern approach for using distance sets
      to decipher structure mapping, including protein folds and conformational changes
      associated with biological activity, is essential. Practical guidelines and hints
      for the technique of SDSL-EPR are described in this chapter, including methods
      for spin labeling the protein backbone, CW-EPR data collection at physiological
      temperatures and two semiquantitative analysis methods to extract interspin
      distance information from the CW-EPR spectra.

PMID- 21713633
TI  - Solution-state nuclear magnetic resonance spectroscopy and protein folding.
AB  - A protein undergoes a variety of structural changes during its folding and
      misfolding and a knowledge of its behaviour is key to understanding the molecular
      details of these events. Solution-state NMR spectroscopy is unique in that it can
      provide both structural and dynamical information at both high-resolution and at
      a residue-specific level, and is particularly useful in the study of dynamic
      systems. In this chapter, we describe NMR strategies and how they are applied in
      the study of protein folding and misfolding.

PMID- 21713634
TI  - Diagnostics for amyloid fibril formation: where to begin?
AB  - Twenty-five proteins are known to form amyloid fibrils in vivo in association
      with disease (Westermark et al., Amyloid 12:1-4, 2005). However, the fundamental
      ability of a protein to form amyloid-like fibrils is far more widespread than in
      just the proteins associated with disease, and indeed this property can provide
      insight into the basic thermodynamics of folding and misfolding pathways. But how
      does one determine whether a protein has formed amyloid-like fibrils? In this
      chapter, we cover the basic steps toward defining the amyloid-like properties of
      a protein and how to measure the kinetics of fibrillization. We describe several
      basic tests for aggregation and the binding to two classic amyloid-reactive dyes,
      Congo Red, and thioflavin T, which are key indicators to the presence of fibrils.

PMID- 21713635
TI  - Probing protein aggregation with quartz crystal microbalances.
AB  - The supra-molecular self-assembly of peptides and proteins is a process which
      underlies a range of normal and aberrant biological pathways in nature, but one
      which remains challenging to monitor in a quantitative way. We discuss the
      experimental details of an approach to this problem which involves the direct
      measurement in vitro of mass changes of the aggregates as new molecules attach to
      them. The required mass sensitivity can be achieved by the use of a quartz
      crystal transducer-based microbalance. The technique should be broadly applicable
      to the study of protein aggregation, as well as to the identification and
      characterisation of inhibitors and modulators of this process.

PMID- 21713636
TI  - Dried and hydrated X-ray scattering analysis of amyloid fibrils.
AB  - Wide angle X-ray scattering is a key technique for the analysis of amyloid
      fibrils that can be used to -confirm the presence of a characteristic cross-beta
      fibril structure and to characterise the arrangement of beta-strands and beta
      sheets within this fibril core. Further structural insight can be obtained by the
      comparison of X-ray scattering data obtained for dried and hydrated fibril
      samples. We describe simple techniques for the preparation of dried and hydrated
      fibril samples for X-ray analysis and the subsequent analysis of X-ray scattering
      patterns using custom built and readily available software.

PMID- 21713637
TI  - Solid-state NMR of amyloid membrane interactions.
AB  - Solid-state NMR pulse sequences often feature fewer pulses and delays than the
      more common solution NMR experiments. This ostensible simplicity, however, belies
      the care with which experimental parameters must be determined, as solid-state
      NMR can be much less forgiving of improper experimental set-up. This is
      especially true of "semi-solid" samples, such as the phospholipid vesicles used
      to study membrane-associated peptides and proteins, which feature prominently in
      misfolding diseases. Protocols for the preparation of multilamellar vesicles for
      solid-state NMR studies of Abeta peptides are described, together with procedures
      for optimization of critical experimental parameters, such as spectral widths,
      delay times, and field strengths for (31)P, (2)H, and (13)C NMR spectroscopy.

PMID- 21713638
TI  - Sedimentation velocity analysis of amyloid fibrils.
AB  - Analytical ultracentrifugation is a classical technique used to study the
      solution behavior of proteins. Experimentally determined sedimentation
      coefficients provide information regarding the size, shape, and interactions of
      biological macromolecules. Sedimentation velocity methods have been used to
      characterize the different aggregation states of amyloid oligomers and fibrils.
      This chapter first describes the theoretical background for sedimentation
      velocity analysis. It then provides experimental protocols for sedimentation
      velocity experiments using the analytical ultracentrifuge. Finally, this chapter
      describes the procedure used to analyze sedimentation velocity data to obtain the
      size distribution of amyloid fibrils and their oligomeric precursors.

PMID- 21713639
TI  - Transmission electron microscopy of amyloid fibrils.
AB  - Transmission Electron Microscopy of negatively stained and cryo-prepared
      specimens allows amyloid fibrils to be visualised at high resolution in a dried
      or a hydrated state, and is an essential method for characterising the morphology
      of fibrils and pre-fibrillar species. We outline the key steps involved in the
      preparation and observation of samples using negative staining and cryo-electron
      preservation. We also discuss methods to measure fibril characteristics, such as
      fibril width, from electron micrographs.

PMID- 21713640
TI  - Surface plasmon resonance spectroscopy: a new lead in studying the membrane
      binding of amyloidogenic transthyretin.
AB  - Surface plasmon resonance (SPR) employs the optical principle of SPR to measure
      changes in mass on a sensor chip surface in real time. Surface chemistry has been
      developed which enables the immoblization of lipid bilayers and determination of
      protein-membrane interactions in real time. In the last decade, the plasma
      membrane has been demonstrated to play an important role in amyloidogenesis and
      cytotoxicity induced by amyloidogenic proteins. SPR provides an ideal way to
      study the membrane binding of amyloidogenic proteins. In this chapter, we
      describe the application of SPR to the study of amyloidogenic transthyretin
      binding to the plasma membrane and artificial lipid bilayers.

PMID- 21713641
TI  - Elucidating the role of metals in Alzheimer's disease through the use of Surface
      Enhanced Laser Desorption/Ionisation time-of-flight mass spectrometry.
AB  - Alzheimer's disease (AD) is a highly heterogeneous and progressive dementia which
      is characterised by a progressive decline in cognitive functioning, selective
      neuronal atrophy, and loss of cortical volume in areas involved in learning and
      memory. However, recent research has indicated that the AD-affected brain is also
      besieged by increases in oxidative stress as well as perturbations to the
      homeostasis of biometals, such as copper and iron. These metals are known to
      interact with the neuropathological hallmark of AD, the beta-amyloid peptide
      (Abeta), in a manner which increases Abeta's neurotoxic effects. This knowledge
      has led to the development of therapeutic measures which act to restore biometal
      homeostasis within the AD brain. This chapter outlines how Surface-Enhanced Laser
      Desorption/Ionisation Time-of-Flight Mass Spectrometry can be used to monitor
      Abeta levels within biological systems as well as describing the use of
      immobilised metal affinity capture in the observation of synthetic Abeta
      peptides.

PMID- 21713642
TI  - In vitro synthesis of primary specific anti-breast cancer antibodies by normal
      human peripheral blood mononuclear cells.
AB  - In this study, we developed a unique in vitro model to mimic the endogenous tumor
      microenvironment to understand the effect of immunotherapy with activated T-cells
      (ATC) armed with anti-CD3 * anti-Her2 bispecific antibody (aATC) on antibody
      response by naive immune cells. This model contained a co-culture of naive
      peripheral blood mononuclear cells (PBMC), breast cancer cells (SK-BR-3), ATC or
      aATC and CpG ODNs. Culture supernatants were tested at various time points for
      anti-SK-BR-3 antibodies by ELISA, Western blot and flow cytometry. PBMC
      cocultured with non-irradiated aATC or irradiated (*) aATC showed significant
      increases in anti-tumor antibody production at day 14 (P < 0.0001) in the
      presence of CpG-ODN compared to unstimulated PBMC cultures (n = 9). Antibody
      specificity was confirmed by ELISA, Western blot and flow cytometry. Co-cultures
      containing *aATC and CpG showed significantly enhanced levels of IgG(2) (P <
      0.001) and cytokines that promote IgG(2) synthesis including IL-13 (P < 0.02),
      IFNgamma (P < 0.01) and GM-CSF (P < 0.05) compared to unstimulated PBMC control
      (n = 3). We show that aATC targeting and lysis of tumor cells induces an anti
      tumor antibody response in our in vitro model. This model provides a unique
      opportunity to evaluate the interactions of T-cells, B-cells, and antigen
      presenting cells leading to specific anti-tumor antibody responses.

PMID- 21713643
TI  - Genome-wide gene expression profiles in response to plastid division
      perturbations.
AB  - Plastids are vital organelles involved in important metabolic functions that
      directly affect plant growth and development. Plastids divide by binary fission
      involving the coordination of numerous protein components. A tight control of the
      plastid division process ensures that: there is a full plastid complement during
      and after cell division, specialized cell types have optimal plastid numbers; the
      division rate is modulated in response to stress, metabolic fluxes and
      developmental status. However, how this control is exerted by the host nucleus is
      unclear. Here, we report a genome-wide microarray analysis of three accumulation
      and replication of chloroplasts (arc) mutants that show a spectrum of altered
      plastid division characteristics. To ensure a comprehensive data set, we selected
      arc3, arc5 and arc11 because they harbour mutations in protein components of both
      the stromal and cytosolic division machinery, are of different evolutionary
      origin and display different phenotypic severities in terms of chloroplast
      number, size and volume. We show that a surprisingly low number of genes are
      affected by altered plastid division status, but that the affected genes encode
      proteins important for a variety of fundamental plant processes.

PMID- 21713646
TI  - Frequency components of systolic blood pressure variability reflect vasomotor and
      cardiac sympathetic functions in conscious rats.
AB  - In this study, after confirming the suppression of autonomic nervous function by
      isoflurane anesthesia using autonomic antagonists, we pharmacologically
      investigated the involvement of vasomotor and cardiac sympathetic functions in
      systolic blood pressure variability (SBPV) frequency components in conscious rats
      at rest and during exposure to low-ambient temperature (LT-exposure, 9 degrees C
      for 90 min). Under unanesthesia, phentolamine administration (alpha-adrenoceptor
      antagonist, 10 mg/kg) decreased the mid-frequency component (MF 0.33-0.73 Hz) and
      inversely increased the high-frequency component (HF 1.3-2.5 Hz). The increased
      HF was suppressed by subsequent treatment with atenolol (beta-adrenoceptor
      antagonist, 10 mg/kg), but not with atropine (muscarinic receptor antagonist, 10
      mg/kg). Moreover, phentolamine administration after atenolol decreased MF, but
      did not increase HF. LT-exposure increased MF and HF; however, phentolamine
      pretreatment suppressed the increased MF during LT-exposure, and atenolol
      pretreatment dose-dependently decreased the increased HF. These results suggest
      that MF and HF of SBPV may reflect alpha-adrenoceptor-mediated vasomotor function
      and beta-adrenoceptor-mediated cardiac sympathetic function, respectively, in the
      conscious state.

PMID- 21713647
TI  - Childhood-onset schizophrenia: the challenge of diagnosis.
AB  - During the past two decades, the Child Psychiatry Branch at the National
      Institute of Mental Health has conducted a longitudinal study (including long
      term prospective follow-up) of childhood-onset schizophrenia, a rare form of the
      disorder. Critical to this research has been accurate diagnosis. Outpatient
      screening has accurately diagnosed 55% of the 121 childhood-onset schizophrenia
      patients in the study to date. However, inpatient observation including drug-free
      observation has proven crucial to ruling out 96 children with alternative
      diagnoses who had been provisionally admitted for inpatient study. Standardized
      clinical ratings from outpatient screening only predicted 62% of these
      nonschizophrenia patients. Historically, medication-free observation was standard
      clinical care for difficult and unusual patients; this should be employed when
      possible in similar situations.

PMID- 21713648
TI  - Mast cell biology: introduction and overview.
AB  - In recent years, the field of mast cell biology has expanded well beyond the
      boundaries of atopic disorders and anaphy laxis, on which it has been
      historically focused. The biochemical and signaling events responsible for the
      development and regulation of mast cells has been increasingly studied, aided in
      large part by novel breakthroughs in laboratory techniques used to study these
      cells. The result of these studies has been a more comprehensive definition of
      mast cells that includes added insights to their overall biology as well as the
      various disease states that can now be traced to defects in mast cells. This
      introductory chapter outlines and highlights the various topics of mast cell
      biology that will be discussed in further detail in subsequent chapters.

PMID- 21713649
TI  - Mast cell progenitor trafficking and maturation.
AB  - Mast cells are derived from the hematopoietic progenitors found in bone marrow
      and spleen. Committed mast cell progenitors are rare in bone marrow suggesting
      they are rapidly released into the blood where they circulate and move out into
      the peripheral tissues. This migration is controlled in a tissue specific manner.
      Basal trafficking to the intestine requires expression of alpha4beta7 integrin
      and the chemokine receptor CXCR2 by the mast cell progenitors and expression of
      MAdCAM-1 and VCAM-1 in the intestinal endothelium; and is also controlled by
      dendritic cells expressing the transcriptional regulatory protein T-bet. None of
      these play a role in basal trafficking to the lung. With the induction of
      allergic inflammation in the lung, there is marked recruitment of committed mast
      cell progenitors to lung and these cells must express alpha4beta7 and alpha4beta1
      integrins. Within the lung there is a requirement for expression of VCAM-1 on the
      endothelium that is regulated by CXCR2, also expressed on the endothelium. There
      is a further requirement for expression of the CCR2/CCL2 pathways for full
      recruitment of the mast cell progenitors to the antigen-inflamed lung.

PMID- 21713650
TI  - Monomeric IgE and mast cell development, survival and function.
AB  - Mast cells play a major role in allergy and anaphylaxis, as well as a protective
      role in immunity against bacteria and venoms (innate immunity) and T-cell
      activation (acquired immunity).1,2 It was long thought that two steps are
      essential to mast cell activation. The first step (sensitization) occurs when
      antigen-specific IgE binds to its high-affinity IgE receptor (FcepsilonRI)
      expressed on the surface of mast cells. The second step occurs when antigen (Ag)
      or anti-IgE binds antigen-specific IgE antibodies bound to FcepsilonRI present on
      the mast cell surface (this mode of stimulation hereafter referred to as IgE+Ag
      or IgE+anti-IgE stimulation, respectively).Conventional wisdom has been that
      monomeric IgE plays only an initial, passive role in mast cell activation.
      However, recent findings have shown that IgE binding to its receptor FcepsilonRI
      can mediate mast cell activation events even in the absence of antigen (this mode
      of stimulation hereafter referred to as IgE(-Ag) stimulation). Different subtypes
      of monomeric IgEs act via IgE(-Ag) stimulation to elicit varied effects on mast
      cells function, survival and differentiation. This chapter will describe the role
      of monomeric IgE molecules in allergic reaction, the various effects and
      mechanisms of action of IgE(-Ag) stimulation on mast cells and what possible
      developments may arise from this knowledge in the future. Since mast cells are
      involved in a variety of pathologic and protective responses, understanding the
      role that monomeric IgE plays in mast cell function, survival and differentiation
      will hopefully lead to better understanding and treatment of asthma and other
      allergic diseases, as well as improved understanding of host response to
      infections.

PMID- 21713651
TI  - Mast cell apoptosis and survival.
AB  - Mast cells are enigmatic cells that are recognized as critical components of our
      immune system. They are strategically localized at the host/environment
      interface, display a long lifespan once situated in tissues and have the ability
      to produce, store and upon activation, release immuno-regulatory molecules. In
      specific acute and chronic conditions, mast cell accumulation, activation and
      release of mediators are important for the initiation and perpetuation of the
      inflammation associated with these disease states. During the past decade,
      regulatory pathways for mast cell survival have been elucidated, which have, in
      part, helped to explain the increased number and survival of mast cells observed
      during inflammatory reactions associated with, e.g., the allergic response. One
      key group of regulators involved in cell survival and apoptosis is the Bcl-2
      family of proteins. The Bcl-2 family consists of pro- and anti-apoptotic members,
      where the balance between these members determines cellular fate via protein
      protein interactions. In this chapter, we will discuss the regulation of mast
      cell apoptosis and survival and how understanding the mechanisms by which Bcl-2
      family members regulate mast cell survival could lead to the identification of
      key proteins that affect the severity of inflammation. This knowledge could be
      used to develop treatments for mast cell disorders such as mastocytosis and other
      inflammatory diseases where mast cells are involved.

PMID- 21713652
TI  - Regulators of Ca(2+) signaling in mast cells: potential targets for treatment of
      mast cell-related diseases?
AB  - A calcium signal is essential for degranulation, generation of eicosanoids and
      optimal production of cytokines in mast cells in response to antigen and other
      stimulants. The signal is initiated by phospholipase C-mediated production of
      inositol1,4,5-trisphosphate resulting in release of stored Ca(2+) from the
      endoplasmic reticulum (ER) and Golgi. Depletion of these stores activates influx
      of extracellular Ca(2+), usually referred to as store-operated calcium entry
      (SOCE), through the interaction of the Ca(2+)-sensor, stromal interacting
      molecule-1 (STIM1 ), in ER with Orai1(CRACM1) and transient receptor potential
      canonical (TRPC) channel proteins in the plasma membrane (PM). This interaction
      is enabled by microtubular-directed reorganization of ER to form ER/PM contact
      points or "punctae" in which STIM1 and channel proteins colocalize. The ensuing
      influx of Ca(2+) replenishes Ca(2+) stores and sustains elevated levels of
      cytosolic Ca(2+) ions-the obligatory signal for mast-cell activation. In
      addition, the signal can acquire spatial and dynamic characteristics (e.g.,
      calcium puffs, waves, oscillations) that encode signals for specific functional
      outputs. This is achieved by coordinated regulation of Ca(2+) fluxes through ATP
      dependent Ca(2+)-pumps and ion exchangers in mitochondria, ER and PM. As
      discussed in this chapter, studies in mast cells revealed much about the
      mechanisms described above but little about allergic and autoimmune diseases
      although studies in other types of cells have exposed genetic defects that lead
      to aberrant calcium signaling in immune diseases. Pharmacologic agents that
      inhibit or activate the regulatory components of calcium signaling in mast cells
      are also discussed along with the prospects for development of novel SOCE
      inhibitors that may prove beneficial in the treatment inflammatory mast-cell
      related diseases.

PMID- 21713653
TI  - Spatio-temporal signaling in mast cells.
AB  - This chapter summarizes the evidence for localized signaling domains in mast
      cells and basophils, with a particular focus on the high affinity IgE receptor,
      FcepsilonRI and its crosstalk with other membrane proteins. It is noteworthy that
      a literature spanning 30 years established the FcepsilonRI as a model receptor
      for studying activation-induced changes in receptor diffusion and lipid raft
      association. Now a combination of high resolution microscopy methods, including
      immunoelectron microscopy and sophisticated fluorescence-based techniques,
      provide new insight into the nanoscale spatial and temporal aspects of receptor
      topography on the mast cell plasma membrane. Physical crosslinking of FcepsilonRI
      with multivalent ligands leads to formation of IgE receptor clusters, termed
      "signaling patches," that recruit downstream signaling molecules. However,
      classes of receptors that engage solely withmono valent ligands can also form
      distinctive signaling patches. The dynamic relationships between receptor
      diffusion, aggregation state, clustering, signal initiation and signal strength
      are discussed in the context of these recent findings.

PMID- 21713654
TI  - The mechanisms of exocytosis in mast cells.
AB  - Upon activation through high affinity IgE receptors (FcepsilonRI), mast cells
      (MCs) can release up to 100% of their content of preformed mediators stored in
      cytoplasmic secretory granules by compound exocytosis. This causes Type I
      immediate hypersensitivity reactions and, in the case of inappropriate activation
      by allergens, the symptoms of allergy. Recent work has uncovered a central role
      of SNARE (Soluble N-ethylmaleimide-Sensitive Factor (NSF) Attachment Protein
      (SNAP) Receptors) proteins in regulating the numerous membrane fusion events
      during exocytosis. This has defined a series of new molecular actors in MC
      exocytosis that participate in the regulation of membrane fusion and the
      connection of the fusion machinery with early signaling events. The purpose of
      this chapter is to describe these proteins and provide a brief overview on their
      mechanism of action.

PMID- 21713656
TI  - Down-regulation of mast cell responses through ITIM containing inhibitory
      receptors.
AB  - The multiple cell types that comprise the immune system provide an efficient
      defense system against invading pathogens and micro-organisms. In general, immune
      cells are activated for disparate functions, such as proliferation, production
      and release of mediators and chemotaxis, as a result of interactions between
      ligands and their matching immunoreceptors. This in turn leads to the recruitment
      and activation of a cascade of second messengers, via their regulators/adaptors,
      that determine the net effect of the initial response. However, activation of
      cells of the immune system must be tightly regulated by a finely tuned interplay
      between activation and inhibition to avoid excessive or inappropriate
      responsiveness and to maintain homeostasis. Loss of inhibitory signals may
      disrupt this balance, leading to various pathological processes such as allergic
      and auto-immune diseases. In this chapter, we will discuss down-regulating
      mechanisms of mast cells focusing on immunoreceptor tyrosine-based inhibition
      motifs (ITIM)-containing inhibitory receptors (IR).

PMID- 21713655
TI  - An emerging role for the lipid mediator sphingosine-1-phosphate in mast cell
      effector function and allergic disease.
AB  - Sphingosine-1-phosphate (S1P) plays important roles regulating functions of
      diverse biological systems, including the immune system. S1P affects immune cell
      function mostly by acting through its receptors at the cell membrane but it can
      also induce S1P receptor-independent responses in the cells where it is
      generated. S1P produced in allergically-stimulated mast cells mediates
      degranulation, cytokine and lipid mediator production and migration of mast cells
      towards antigen by mechanisms that are both S1P receptor-dependent and
      independent. Even in the absence of an antigen challenge, the differentiation and
      responsiveness of mast cells can be affected by chronic exposure to elevated S1P
      from a nonmast cell source, whichmay occur under pathophysiological conditions,
      potentially leading to the hyper-responsiveness of mast cells. The role of S1P
      extends beyond the regulation of the function of mast cells to the regulation of
      the surrounding or distal environment. S1P is exported out of antigen-stimulated
      mast cells and into the extracellular space and the resulting S1P gradient within
      the tissue may influence diverse surrounding tissue cells and several aspects of
      the allergic disease, such as inflammation or tissue remodeling. Furthermore,
      recent findings indicate that vasoactive mediators released systemically by mast
      cells induce the production of S1P in nonhematopoietic compartments, where it
      plays a role in regulating the vascular tone and reducing the hypotension
      characteristic of the anaphy lactic shock and thus helping the recovery. The dual
      actions of S1P, promoting the immediate response of mast cells, while controlling
      the systemic consequences of mast cell activity will be discussed in detail.

PMID- 21713657
TI  - The mast cell in innate and adaptive immunity.
AB  - Mast cells (MCs) were once considered only as effector cells in pathogenic IgE-
      and IgG-mediated responses such as allergy. However, developments over the last
      15 years have suggested that MCs have evolved in vertebrates as beneficial
      effector cells that are involved in the very first inflammatory responses
      generated during infection. This pro-inflammatory environment has been
      demonstrated to be important for initiating innate responses in many different
      models of infection and more recently, in the development of adaptive immunity as
      well. Interestingly this latter finding has led to the discovery that small MC
      activating compounds can behave as adjuvants in vaccine formulations. Thus, our
      continued understanding of the MC in the context of infectious disease is likely
      to not only expand our scope of the MC in the normal processes of immunity, but
      provide new therapeutic targets to combat disease.

PMID- 21713658
TI  - Mast cells and immunoregulation/immunomodulation.
AB  - Mast cells often represent one of the first cells of the immune system to
      interact with environmental antigens, invading pathogens or environmentally
      derived toxins. Mast cells also can undergo alterations in phenotype, anatomic
      distribution and numbers during innate or adaptive immune responses. In addition
      to their well-known roles as effector cells during IgE- and antigen-induced
      allergic reactions, mast cells can be activated by many other signals, including
      some that are derived directly from pathogens or which are generated during
      innate or adaptive immune responses. Mast cells also express many costimulatory
      molecules with immunoregulatory activities and can secrete many products that can
      positively or negatively regulate immune responses. In this chapter, we describe
      mouse models used for analyzing mast-cell function in vivo and illustrate how
      such models have been used to identify positive or negative immunomodulatory
      roles for mast cells during specific innate or adaptive immune responses. We also
      briefly describe some of the mast-cell functions, products and surface receptors
      that have the potential to permit mast cells to promote or suppress immune
      responses that can either enhance host defense or contribute to disease.

PMID- 21713660
TI  - Mast cells in lung inflammation.
AB  - Mast cells play an important role in the lung in both health and disease. Their
      primary role is to initiate an appropriate program of inflammation and repair in
      response to tissue damage initiated by a variety of diverse stimuli. They are
      important for host immunity against bacterial infection and potentially in the
      host immune response to non small cell lung cancer. In situations of ongoing
      tissue damage, the sustained release of numerous pro-inflammatory mediators,
      proteases and cytokines, contributes to the pathophysiology of lung diseases such
      as asthma and interstitial lung disease. A key goal is the development of
      treatments which attenuate adverse mast cell function when administered
      chronically to humans in vivo. Such therapies may offer a novel approach to the
      treatment of many life-threatening diseases.

PMID- 21713661
TI  - Mast cells, angiogenesis and cancer.
AB  - Mast cells (MCs) were first described by Paul Ehrlich 1 in his doctoral thesis.
      MCs have long been implicated in the pathogenesis of allergic reactions and
      certain protective responses to parasites. As most tumors contain inflammatory
      cell infiltrates, which often include plentiful MCs, the question as to the
      possible contribution of MCs to tumor development has progressively been
      emerging. In this chapter, the specific involvement of MCs in tumor biology and
      tumor fate will be considered, with particular emphasis on the capacity of these
      cells to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis.
      Data from experimental carcinogenesis and from different tumor settings in human
      pathology will be summarized. Information to be presented will suggest that MCs
      may serve as a novel therapeutic target for cancer treatment.

PMID- 21713659
TI  - Mast cell proteases as protective and inflammatory mediators.
AB  - Proteases are the most abundant class of proteins produced by mast cells. Many of
      these are stored in membrane-enclosed intracellular granules until liberated by
      degranulating stimuli, which include cross-linking of high affinity IgE receptor
      F(c)epsilonRI by IgE bound to multivalent allergen. Understanding and separating
      the functions of the proteases is important because expression differs among mast
      cells in different tissue locations. Differences between laboratory animals and
      humans in protease expression also influence the degree of confidence with which
      results obtained in animal models of mast cell function can be extrapolated to
      humans. The inflammatory potential of mast cell proteases was the first aspect of
      their biology to be explored and has received the most attention, in part because
      some of them, notably tryptases and chymases, are biomarkers of local and
      systemic mast cell degranulation and anaphylaxis. Although some of the proteases
      indeed augment allergic inflammation and are potential targets for inhibition to
      treat asthma and related allergic disorders, they are protective and even anti
      inflammatory in some settings. For example, mast cell tryptases may protect from
      serious bacterial lung infections and may limit the "rubor" component of
      inflammation caused by vasodilating neuropeptides in the skin. Chymases help to
      maintain intestinal barrier function and to expel parasitic worms and may support
      blood pressure during anaphylaxis by generating angiotensin II. In other life-or
      death examples, carboxypeptidase A3 and other mast cell peptidases limit systemic
      toxicity of endogenous peptideslike endothelin and neurotensin during septic
      peritonitis and inactivate venom-associated peptides. On the other hand, mast
      cell peptidase-mediated destruction of protective cytokines, like IL-6, can
      enhance mortality from sepsis. Peptidases released from mast cells also influence
      nonmast cell proteases, such as by activating matrix metalloproteinase cascades,
      which are important in responses to infection and resolution of tissue injury.
      Overall, mast cell proteases have a variety of roles, inflammatory and anti
      inflammatory, protective and deleterious, in keeping with the increasingly well
      appreciated contributions of mast cells in allergy, tissue homeostasis and innate
      immunity.

PMID- 21713662
TI  - Metabotropic actions of kainate receptors in the control of GABA release.
AB  - Kainate receptors (KARs) are members of the family of ionotropic glutamate
      receptors (iGluRs) which also include NMDA and AMPA receptors. As ionotropic
      receptors, KARs have been characterized, pre and postsynaptically, in several
      brain regions. In this chapter we review evidence that suggests that KARs mediate
      some of their effects without invoking ion-fluxes. Beginning with seminal
      experiments described some ten years ago, when the notion of a metabotropic
      action of KAR was first posited in the modulation of GABA release from
      hippocampal interneurons, increasingly, there have been reports indicating that
      some KAR functions overtly depend on G-protein activation and involve the
      participation of intracellular signalling cascades. Thus, KAR activation
      instigates a cascade involving G(i/o), phospholipase C and protein kinase C to
      suppress the release of GABA and therefore underpins disinhibition of pyramidal
      cells in the CA1 region of the hippocampus. This type of metabotropic function of
      KARs in controlling GABA release represents an additional level of activity
      dependent control of synaptic inhibition which is independent of any ionotropic
      activity of KARs.

PMID- 21713663
TI  - In the developing hippocampus kainate receptors control the release of GABA from
      mossy fiber terminals via a metabotropic type of action.
AB  - Kainate receptors (KARs) are glutamate-gated ion channels assembled from various
      combinations of GluK1-GluK5 subunits with different physiological and
      pharmacological properties. In the hippocampus, KARs expressed at postsynaptic
      sites mediate a small component of excitatory postsynaptic currents while at
      presynaptic sites they exert a powerful control on transmitter release at both
      excitatory and inhibitory connections. KARs are developmentally regulated and
      play a key role in several developmental processes including neuronal migration,
      differentiation and synapse formation. Interestingly, they can signal through a
      canonical ionotropic pathway but also through a noncanonical modality involving
      pertussis toxin-sensitive G proteins and downstream signaling molecules.In this
      Chapter some of our recent data concerning the functional role of presynaptic
      KARs in regulation of transmitter release from immature mossy fiber terminals and
      in synaptic plasticity processes will be reviewed. Early in postnatal
      development, MFs release into their targeted neurons mainly GABA which is
      depolarizing and excitatory. Endogenous activation of GluK1 KARs localized on MF
      terminals by glutamate present in the extracellular space down regulates GABA
      release, leading sometimes to synapse silencing. The depressant effect of GluK1
      on MF responses is mediated by a metabotropic process, sensitive to pertussis
      toxin and phospholipase C (PLC) along the transduction pathway downstream to G
      protein activation. Blocking PLC with the selective antagonist U73122, unmasks
      the potentiating effect of GluK1 on MF-evoked GABAergic currents, which probably
      depend on the ionotropic type of action of these receptors.In addition, GluK1
      KARs dynamically regulate the direction of spike-time dependent plasticity, a
      particular form of Hebbian type of learning which consists in bidirectional
      modifications in synaptic strength according to the temporal order of pre and
      postsynaptic spiking. At immature MF-CA3 synapses pairing MF stimulation with
      postsynaptic spiking and vice versa induces long term depression of MF-evoked
      GABAergic currents. In the case of positive pairing synaptic depression can be
      switched into spike-time dependent potentiation by blocking GluK1 KARs with UBP
      302. The depressant action exerted by GluK1 KARs on MF responses would prevent
      the excessive activation of the CA3 associative network by the excitatory action
      of GABA early in postnatal development.

PMID- 21713664
TI  - Localization and functions of kainate receptors in the basal ganglia.
AB  - Kainate receptors (KARs) are one of the three subtypes of ionotropic glutamate
      receptors in the CNS. These receptors are widely expressed pre- and
      postsynaptically throughout the brain. Thus, kainate receptor activation mediates
      a large variety of pre- and postsynaptic effects on either glutamatergic or
      GABAergic synaptic transmission. Although ionotropic functions for KAR have been
      described in multiple brain regions, there is considerable evidence from various
      CNS regions that KARs activation modulates GABA release through either G-protein
      dependent metabotropic pathway or secondary activation of G-protein coupled
      receptors. In the present chapter, we provide further evidence supporting that
      these two pathways are also involved in the modulation of GABA release in
      specific basal ganglia nuclei. Because of their more subtle effects on
      neurotransmisison regulation than other ionotropic glutamate receptors, KARs
      represent interesting targets for the future development of pharmacotherapy for
      basal ganglia diseases.

PMID- 21713665
TI  - Metabotropic actions of kainate receptors in the control of glutamate release in
      the hippocampus.
AB  - Kainate-type glutamate receptors (KARs) structurally present the credentials of
      the other ionotropic glutamate receptor (iGluR) family members (NMDA and AMPA
      receptors), but functionally often purport examples of a metabotropic mode of
      operation. In the present chapter, we describe these metabotropic roles of KARs
      in the modulation of glutamate release in the hippocampus at CA3 Schaffer
      Collateral (SC)-CA1 Pyramidal Cell (PC) synapses and dentate gyrus granule cell
      Mossy Fiber (MF)-CA3 PC synapses. As autoreceptors on SC terminals, KARs inhibit
      the release of glutamate at SC-CA1 PC synapses through a mechanism dependent on a
      pertussis toxin-sensitive G(i/o) protein thought to couple via its Gbetagamma
      subunit to a decrease in Ca(2+) channel function. At MF-CA3 PC synapses,
      autoreceptors on MF terminals respond diametrically depending on the agonist
      concentration. At low KA concentrations (< 100 nM), a G-protein-independent
      process invokes the activation of proteins kinase A (PKA) to effect a
      facilitation of glutamate release. This facilitation possibly involves the Ca(2+)
      dependent (rather than GPCR-dependent) activation of adenylate cyclase (AC). At
      high KA concentrations (<100 nM), a mechanism involving a pertussis toxin
      sensitive G(i/o) protein is invoked to inhibit AC activity and thereby suppress
      PKA activity. Taken together with the heterosynaptic regulation of GABA release
      by KARs working with a metabotropic modus operandi, there is therefore compelling
      evidence that these ionotropic glutamate receptors are involved in a noncanonical
      modulation of glutamate release that does not rely on their typical ionotropic
      activity.

PMID- 21713666
TI  - Metabotropic actions of kainate receptors in the regulation of I(sAHP) and
      excitability in CA1 pyramidal cells.
AB  - Kainate receptors (KARs) mediate postsynaptic responses in CA3 pyramidal cells
      and CA1 interneurones in the hippocampus. In CA1 pyramidal cells knockout studies
      have inidcated the presence of functional GluR6-containing KARs, however in this
      region they made no ionotropic contribution to the synaptic responses. In the
      meantime, a metabotropic function was reported for presynaptic KARs modulating
      transmitter release in CA1. We examined the possibility that KARs in CA1
      pyramidal cells have a metabotropic function. Kainate is known to inhibit a slow
      afterhyperpolarization current that regulates excitability in hippocampus and can
      be modulated by a number of G protein coupled receptors. We showed that KARs
      activation reduces slow afterhyperpolarization current in CA1 pyramidal cells via
      metabotropic action and elucidated the transduction mechanism(s) underlying this
      action.

PMID- 21713667
TI  - Kainate receptors with a metabotropic signature enhance hippocampal excitability
      by regulating the slow after-hyperpolarization in CA3 pyramidal neurons.
AB  - Most of our knowledge of the synaptic function of kainate receptors stems from a
      detailed analysis of synaptic transmission between dentate granule cells and CA3
      pyramidal neurons, where kainate receptors mediate a slow excitatory current with
      integrative properties ideally suited for repetitive neuronal firing. Besides
      this well characterized ionotropic effect of kainate receptors, they can also
      enhance neuronal excitability by inhibiting the slow Ca(2+) activated K(+)
      current I(sAHP) via a G-protein coupled mechanism. This phenomenon is associated
      with Ca(2+) mobilization and protein-kinase activation and ultimately leads to
      modulation of ion channels responsible for intrinsic electrical properties such
      as firing adaptation. The significance for CNS function of these newly emerging
      metabotropic kainate receptors is poorly understood and as yet proteomic analysis
      of kainate receptors has yielded little information on signaling molecules
      associated with the kainate receptor ionophore. This chapter covers the key
      findings that have led to the proposal that high-affinity postsynaptic kainate
      receptors trigger a form of metabotropic signaling regulating I(sAH P) and
      neuronal firing in CA3 hippocampal neurons.

PMID- 21713668
TI  - Metabotropic actions of kainate receptors in dorsal root ganglion cells.
AB  - Kainate receptors are widely distributed in the CNS, but also in the PNS. Dorsal
      root ganglia are enriched in this subtype of glutamate ionotropic receptors. In
      addition to their activity as ligand-gated ion channels, kainate receptors
      exhibit other properties already characterized in other systems, such as
      hippocampus, i.e., their ability to induce a metabotropic cascade signalling,
      through G-protein and PKC activation. With a very similar actuation mechanism as
      formerly described in the CNS, kainate receptors in the DRG also present other
      differentiated features, such as the Ca(2+) channel blockade and a self
      regulation property. The peculiarity of these neurons has served to progress the
      study of kainate receptors. Nevertheless, many other physiological functions of
      these receptors remain unclear, as does the related molecular nature of the
      metabotropic cascade and the involvement of this signalling pathway with sensory
      transmission of pain.

PMID- 21713669
TI  - Role of kainate receptors in network activity during development.
AB  - Distinct populations of kainate-type ionotropic glutamate receptors (KARs),
      located at various cell types and subcellular compartments and utilizing diverse
      downstream signaling mechanisms, represent an intricate system with large
      capacity for modulatory effects ranging from synapse-specific changes to
      alterations in the excitability of large neuronal ensembles. However, the way the
      diverse functions ascribed for KARs are utilized under different physiological
      and pathological conditions to regulate activity at the level of neuronal
      networks is still largely unclear. Here, we address the data regarding functions
      of KARs in the regulation of network activity in the hippocampus, with a main
      focus on their roles during early postnatal development. We further discuss the
      evidence suggesting that KAR mediated signaling during the immature type network
      activity is involved in the formation and maturation of glutamatergic synapses.

PMID- 21713670
TI  - Kainate receptor modulation by sodium and chloride.
AB  - The kainate-type glutamate receptor displays strong modulation by monovalent
      anions and cations. This modulation is independent of permeation of the ion
      channel. Instead, structural, computational and biophysical evidence shows that
      receptor activity is controlled by binding of sodium and chloride ions at sites
      that stabilize active dimers of glutamate binding domains. Modulation by
      monovalent ions is a surprisingly general property across ion channel families.
      However, evidence of a physiological role for ion-dependent effects on glutamate
      receptors is lacking, perhaps reflecting the adventitious use of ions as
      structural components of the kainate receptor. "ergo, Hercules, vita humanior
      sine sale non quit degree [...]" "Heaven known, a civilized life is impossible
      without salt" -Pliny the Elder, Natural History XXXI 88.

PMID- 21713671
TI  - BTB-Kelch proteins and ubiquitination of kainate receptors.
AB  - Kainate receptors (KAR) form a class of glutamate receptors that have been
      implicated in epilepsy, stroke, Alzheimer's and neuropathic pain.1 KAR subtypes
      are known to be segregated to specific locations within neurons and play
      significant roles in synaptic transmission and plasticity.2 Increasing evidence
      suggests a the role for ubiqutination in regulating the number of synaptic
      neurotransmitter receptors.3-5 The ubiquitin pathway consists of activation (E1),
      conjugation (E2) and ligation (E3). Cullins form the largest family of E3 ligase
      complexes. We have recently shown that the BTB/Kelch domain proteins, actinfilin
      and mayven, bind both Cul3 and specific KAR subtypes (GluR6 and GluR5-2b) to
      target these KARs for ubiquitination and degradation.5 In this chapter we will
      review how these interactions occur, what they mean for the stability of KARs and
      their associated proteins and how, in turn, they may affect synaptic functions in
      the central nervous system.

PMID- 21713673
TI  - Finding the exosome.
AB  - We describe the events surrounding the identification of the exosome complex and
      the subsequent early development of the field. Like many scientific discoveries,
      the initial identification and characterization of the exosome was based on a
      combination of skill, good fortune-and the availability of cutting edge
      technology.

PMID- 21713674
TI  - Structural components and architectures of RNA exosomes.
AB  - A large body of structural work conducted over the past ten years has elucidated
      mechanistic details related to 3' to 5' processing and decay of RNA substrates by
      the RNA exosome. This chapter will focus on the structural organization of
      eukaryotic exosomes and their evolutionary cousins in bacteria and archaea with
      an emphasis on mechanistic details related to substrate recognition and to 3' to
      5' phosphorolytic exoribonucleolytic activities of bacterial and archaeal
      exosomes as well as the hydrolytic exoribonucleolytic and endoribonucleolytic
      activities of eukaryotic exosomes. These points will be addressed in large part
      through presentation of crystal structures of phosphorolytic enzymes such as
      bacterial RNase PH, PNPase and archaeal exosomes and crystal structures of the
      eukaryotic exosome and exosome sub-complexes in addition to standalone structures
      of proteins that catalyze activities associated with the eukaryotic RNA exosome,
      namely Rrp44, Rrp6 and their bacterial counterparts.

PMID- 21713675
TI  - The archaeal exosome.
AB  - The archaeal exosome is a protein complex with structural similarities to the
      eukaryotic exosome and bacterial PNPase. Its catalytic core is formed by
      alternating Rrp41 and Rrp42 polypeptides, arranged in a hexameric ring. A
      flexible RNA binding cap composed of the evolutionarily conserved proteins Rrp4
      and/or Csl4 is bound at the top of the ring and seems to be involved in
      recruitment of specific substrates and their unwinding. Additionally, the protein
      complex contains an archaea-specific subunit annotated as DnaG, the function of
      which is still unknown. The archaeal exosome degrades RNA phosphorolytically in
      3' to 5' direction. In a reverse reaction, it synthesizes heteropolymeric RNA
      tails using nucleoside diphosphates. The functional similarity between the
      archaeal exosome and PNPase shows that important processes of RNA degradation and
      posttranscriptional modification in Archaea are similar to the processes in
      Bacteria and organelles.

PMID- 21713676
TI  - The exosomes of trypanosomes and other protists.
AB  - The archaeal exosome contains three heterodimeric RNase PH subunits, forming a
      hexamer with RNase activity; on top sits a trimer of two different SI domain
      proteins. In animals and yeast, six different, but related subunits form the
      RNase PH-like core, but these lack enzyme activity; there are three different Si
      domain proteins and enzyme activity is provided by the endo/exonuc lease Rrp44 or
      mainly in the nuclear exosome-the Rnase D enzyme Rrp6. Trypanosomes diverged from
      yeast and mammals very early in eukaryotic evolution. The trypanosome exosome is
      similar in subunit composition to the human exosome, but instead of being an
      optional component, trypanosome RRP6 is present in the nucleus and cytoplasm and
      is required for exosome stability. As in human cells and yeast, the trypanosome
      exosome has been shown to be required for processing and quality control of rRNA
      and to be involved in mRNA degradation. Electron microscopy results for a
      Leishmania exosome suggest that RRP6 is located on the side of the RnasePH ring,
      interacting with several exosome core proteins. Results of a search for exosome
      subunits in the genomes of widely diverged protists revealed varied exosome
      complexity; the Giardia exosome may be as simple as that of Archaea.

PMID- 21713677
TI  - The exosome and 3'-5' RNA degradation in plants.
AB  - One of the most versatile RNA degradation machines in eukaryotes is the 3'-5' RNA
      exosome. It consists of nine conserved subunits forming the core complex, which
      associates with active ribonucleases, RNA binding proteins, helicases and
      additional co-factors. While yeast and human exosome core complexes are
      catalytically inactive, the plant core complex has probably retained a
      phosphorolytic activity. Intriguingly, the down-regulation of individual subunits
      of the plant core complex in Arabidopsis mutants led to distinct developmental
      defects, suggesting an unequal contribution of the core subunits to the in vivo
      activities of the plant exosome complex. In addition, some of the plant core
      subunits as well as some associated factors are encoded by duplicated genes,
      which may have both overlapping and specific functions. Together, these results
      suggest an unique and complex organisation of exosome-mediated RNA degradation
      processes in plants. This chapter reviews our current knowledge of plant exosomes
      and discusses the impact of 3'-5' RNA degradation on the posttranscriptional
      control of plant genome expression.

PMID- 21713678
TI  - Catalytic properties of the eukaryotic exosome.
AB  - The eukaryotic exosome complex is built around the backbone of a 9-subunit ring
      similar to phosporolytic ribonucleases such as RNase PH and polynucleotide
      phosphorylase (PNPase). Unlike those enzymes, the ring is devoid of any
      detectable catalytic activities, with the possible exception of the plant version
      of the complex. Instead, the essential RNA decay capability is supplied by
      associated hydrolytic ribonucleases belonging to the Dis3 and Rrp6 families. Dis3
      proteins are endowed with two different activities: the long known processive 3'
      5' exonucleolytic one and the recently discovered endonucleolytic one. Rrp6
      proteins are distributive exonucleases. This chapter will review the current
      knowledge about the catalytic properties of theses nucleases and their interplay
      within the exosome holocomplex.

PMID- 21713679
TI  - Functions of the cytoplasmic exosome.
AB  - The exosome consists of a core of ten essential proteins that includes the
      ribonuclease Rrp44p and is present in both the cytoplasm and nucleus of
      eukaryotic cells. The cytoplasmic exosome has been extensively characterized in
      the budding yeast Saccharomyces cerevisiae and some characterization of its
      metazoan counterpart indicates that most functional aspects are conserved. These
      studies have implicated the cytoplasmic exosome in the turnover of normal
      cellular mRNAs, as well as several mRNA surveillance pathways. For this, the
      exosome needs a set of four proteins that do not partake in nuclear exosome
      functions. These cofactors presumably direct the exosome to specific cytoplasmic
      RNA substrates. Here, we review cofactors and functions of the cytoplasmic
      exosome and provide unanswered questions on the mechanisms of cytoplasmic exosome
      function.

PMID- 21713680
TI  - Rrp6, rrp47 and cofactors of the nuclear exosome.
AB  - This chapter reviews the present state of knowledge on the activity of enzymes
      that function with the RNA exosome in the nucleus. In this compartment, the
      exosome interacts physically and functionally with the exoribonuclease Rrp6 and
      several cofactors, most prominently Rrp47 and the TRAMP complex. These
      interactions decide the fate of RNA precursors from transcription through the
      formation of mature ribonucleoprotein particles (RNPs) and the export of the RNPs
      to the cytoplasm. The nuclear exosome catalyzes the formation of the mature 3'
      ends of many of these RNAs, but in other cases degrades the RNAs to
      mononucleotides. Cofactors such as Mpp6, TRAMP and the Nrd1/Nab3 complex play
      important roles in determining the outcome of the interaction of RNPs with the
      nuclear exosome. The details that govern the specificity of these decisions
      remain a rich source for future investigation.

PMID- 21713681
TI  - The exosome and heterochromatin : multilevel regulation of gene silencing.
AB  - Heterochromatic silencing is important for repressing gene expression, protecting
      cells against viral invasion, maintaining DNA integrity and for proper chromosome
      segregation. Recently, it has become apparent that expression of eukaryotic
      genomesis far more complex than had previously been anticipated. Strikingly, it
      has emerged that most of the genome is transcribed including intergenic regions
      and heterochromatin, calling for us to re-address the question of how gene
      silencing is regulated and re-evaluate the concept ofheterochromatic regions of
      the genome being transcriptionally inactive. Although heterochromatic silencing
      can be regulated at the transcriptional level, RNA degrading activities supplied
      either by the exosome complex or RNAi also significantly contribute to this
      process. The exosome also regulates noncoding RNAs (ncRNAs) involved in the
      establishment of heterochromatin, further underscoring its role as the major
      cellular machinery involved in RNA processing and turn-over. This multilevel
      control of the transcriptome may be utilized to ensure greater accuracy of gene
      expression and allow distinction between functional transcripts and background
      noise. In this chapter, we will discuss the regulation of gene silencing across
      species, with special emphasis on the exosome's contribution to the process. We
      will also discuss the links between transcriptional and posttranscriptional
      mechanisms for gene silencing and their impact on the regulation of eukaryotic
      transcriptomes.

PMID- 21713682
TI  - Control of cryptic transcription in eukaryotes.
AB  - Over the last few years, the development of large-scale technologies has
      radically modified our conception of genome-wide transcriptional control by
      unveiling an unexpected high complexity of the eukaryotic transcriptome. In
      organisms ranging from yeast to human, a considerable number of novel small RNA
      species have been discovered in regions that were previously thought to be
      incompatible with high levels of transcription. Intriguingly, these transcripts,
      which are rapidly targeted for degradation by the exosome, appear to be devoid of
      any coding potential and may be the consequence of unwanted transcription events.
      However, the notion that an important fraction of these RNAs represent by
      products of regulatory transcription is progressively emerging. In this chapter,
      we discuss the recent advances made in our understanding of the shape of the
      eukaryotic transcriptome. We also focus on the molecular mechanisms that cells
      exploit to prevent cryptic transcripts from interfering with the expression of
      protein-coding genes. Finally, we summarize data obtained in different systems
      suggesting that such RNAs may play a critical role in the regulation of gene
      expression as well as the evolution of genomes.

PMID- 21713683
TI  - The human exosome and disease.
AB  - Long before the RNA degrading exosome was first described in the yeast
      Saccharomyces cerevisiae, the use of autoantibodies found in the sera of certain
      autoimmune patients allowed the identification of a complex of polypeptides which
      later appeared to be the human exosome. Today, the most extensively documented
      association of the exosome with disease is still its targeting by the immune
      system of such patients. The highest frequency of autoantibodies to components of
      the exosome complex is found in polymyositis-scleroderma overlap patients and
      therefore the exosome is termed PM/Scl autoantigen in the autoimmune field. More
      recently, one of the core components of the exosome was identified as a protein
      associated with chronic myelogenous leukemia. In this chapter we will describe
      the identification of the PM/Scl autoantigen from a historical perspective,
      discuss our current knowledge on the occurrence of autoantibodies to exosome
      components in autoimmune diseases and end with the data that connect the exosome
      with cancer.

PMID- 21713696
TI  - [Choice and technical problems of digestive tract reconstruction in laparoscopic
      gastrointestinal surgery].
AB  - Gastrointestinal tract reconstruction is a key procedure in laparoscopic surgery
      for gastrointestinal diseases. The reconstruction procedure in laparoscopic
      surgery is not superior to conventional surgery. Reconstruction procedures such
      as Billroth I, Billroth II( and Roux-en-Y anastomosis are widely used in
      laparoscopic assisted distal gastrectomy, while esophagojejunostomy by Roux-en-Y
      reconstruction is a reasonable option for laparoscopic assisted total
      gastrectomy. The OrVil technique provides an easier alternative to complete the
      esophagojejunostomy. Esophagogastrostomy is mainly used in laparoscopic assisted
      proximal gastrectomy. Colorectal anastomosis with double stapling technique and
      coloanal anastomosis with hand-sewn technique are common reconstruction
      procedures in laparoscopic surgery for mid and low rectal diseases. In
      laparoscopic colectomy, a small incision is usually used to facilitate the
      reconstruction extracorporeally. It is believed that innovation of
      instrumentation in the near future could bring us safer reconstruction devices
      with better efficiency and quality for laparoscopic surgery.

PMID- 21713697
TI  - [Use of uncut Roux-en-Y reconstruction after distal gastrectomy for gastric
      cancer].
AB  - OBJECTIVE: To evaluate the clinical efficacy of uncut Roux-en-Y reconstruction
      after distal gastrectomy for gastric cancer. METHODS: Clinical data of 419
      patients who underwent distal gastrectomy for gastric cancer with complete follow
      up data between March 2005 and March 2008 in the Cancer Institute and Hospital of
      Tianjin Medical University. Patients were divided into B I (138 cases with
      Billroth I reconstruction), M-B II (108 cases with modified Billroth II
      reconstruction), RY (46 cases with Roux-en-Y reconstruction) and Uncut RY (127
      cases with uncut Roux-en-Y reconstruction) according to reconstructive methods.
      RESULTS: Patients in the Uncut RY group had a larger tumor diameter, more T3, and
      poorer stage of disease compared to those in the B I (P<0.05). In Uncut RY group,
      the operative time and postoperative hospital stay were(132.6+/-19.2) minutes and
      (10.4+/-1.2) days respectively, shorter than those in RY group (142.5+/-11.7)
      minutes and (12.1+/-3.7) days(both P<0.05), alkaline reflex gastritis rate was
      3.2%, lower than that in B I group (24.6%, P<0.05) and M-B II group (25.9%,
      P<0.05). Marginal ulcer rate in uncut RY group was lower compared to M-B II group
      (P=0.019), and incidence of Roux-en-Y stasis syndrome was less compared to RY
      group (P=0.000). CONCLUSIONS: The uncut Roux-en-Y reconstruction is both feasible
      and safe. It can prevent alkaline reflex gastritis and Roux-en-Y stasis syndrome.
      It may be the preferred technique for reconstruction after distal gastrectomy.

PMID- 21713698
TI  - [Impact of techniques for gastrointestinal tract reconstruction following
      gastrectomy on pancreatic beta-cell function in patients with type 2 diabetes
      mellitus].
AB  - OBJECTIVE: To evaluate the impact of different techniques for gastrointestinal
      tract reconstruction on postoperative pancreatic beta-cell function in patients
      with type 2 diabetes mellitus (T2DM). METHODS: Twenty-three patients with gastric
      cancer and T2DM were studied. Techniques for reconstruction included Billroth I
      (n=13) and bypass procedures(Billroth II n=4 and Roux-en-Y anastomosis n=6).
      Pancreatic beta-cell function was evaluated by oral glucose tolerance test
      (OGTT). Serum insulin was measured by electrochemiluminescence immunoassay and
      blood glucose by glucose oxidase method. HOMA-IR and HOMA-beta were assessed.
      RESULTS: T2DM remission rate was 90% (9/10) in the bypass group, and 23% (3/13)
      in Billroth I group (P<0.01). Glycosylated hemoglobin A1c and glycated hemoglobin
      HbA1 were improved significantly in patients after bypass procedures(P<0.05), but
      the difference in Billroth I group was not statistically significant (P>0.05).
      OGTT showed that fasting and post-glucose load plasma glucose at each time point
      were significantly lower in the bypass group compared to the Billroth I group. At
      30 minutes and 60 minutes after glucose load, insulin levels and insulin release
      index were significantly higher in the bypass group compared to Billroth I(
      group, as were levels of HOMA-beta and DeltaI30/DeltaG30 in the bypass
      group(P<0.05). CONCLUSION: Gastrointestinal bypass following gastrectomy may
      induce resolution of T2DM and improve beta-cells function.

PMID- 21713699
TI  - [Use of antiperistaltic cecoproctostomy in colorectal reconstruction].
AB  - OBJECTIVE: To explore the feasibility and functional outcome of antiperistaltic
      cecoproctostomy in colorectal reconstruction. METHODS: Fifty-six patients who
      underwent antiperistaltic cecoproctostomy were retrospectively studied.
      Indications for antiperistaltic cecoproctostomy included slow transit
      constipation(n=44), synchronous colon cancer or colonic polyps(n=5), acute
      obstructing left colon carcinoma(n=4), and adult megacolon(n=3). RESULTS: Short
      term postoperative complications included wound infections(n=5), 3 lymphatic
      leakages(n=3), and inflammatory small bowel obstruction(n=1). One month after
      antiperistaltic cecoproctostomy, the median frequency of daily bowel movement was
      4.0(range, 2-6). After a median follow-up of 4 years(range, 1 month to 7 years),
      the median daily bowel frequency was 2.5(range, 0.5-4.0). Five patients suffered
      from long-term postoperative complications including small bowel
      obstruction(n=3), incision hernia(n=1), and mild cecal dilatation(n=1). The mean
      Wexner incontinence score was 4.2+/-1.1. CONCLUSION: Antiperistaltic
      cecoproctostomy is safe and effective for colorectal reconstruction.

PMID- 21713700
TI  - [Antecolic versus retrocolic gastroenteric anastomosis for laparoscopic Roux-en-Y
      gastric bypass: a prospective randomized control trial].
AB  - OBJECTIVE: To compare short-term postoperative outcomes between antecolic and
      retrocolic laparoscopic Roux-en-Y gastric bypass(LRYGB). METHODS: Forty obesity
      patients were admitted into The First Affiliated Hospital of Jinan University
      from March 2008 to July 2010. All patients were randomly assigned to undergo
      antecolic (group A, 20 cases) and retrocolic (group B, 20 cases) gastroenteric
      anastomosis. Short-term outcomes were compared. RESULTS: LRYGB procedures were
      successfully performed in all the 40 patients. There were no significant
      differences between the two groups in estimated blood loss during surgery, time
      to flatus passage, time to resumption of oral intake, or length of postoperative
      hospital stay. The operation time was longer in group B than that in group A
      [(163.4+/-28.1) min vs.(131.8+/-22.7) min, P<0.05]. There were no patients
      developed internal hernia or anastomotic leakage in either group. Comparison of
      short-term gastrointestinal symptoms after surgery showed no statistical
      significance. CONCLUSIONS: Although retrocolic procedure may be closer to
      anatomical structure, antecolic and retrocolic anastomosis have comparable short
      term outcomes after surgery. Further study is warranted to investigate long-term
      outcomes.

PMID- 21713701
TI  - [Influence of digestive tract reconstruction techniques on plasma ghrelin level
      and body mass index after subtotal gastrectomy].
AB  - OBJECTIVE: To study the impact of digestive tract reconstruction techniques on
      plasma ghrelin level and body mass index (BMI) after subtotal gastrectomy.
      METHODS: Eighty-one patients undergoing subtotal gastrectomy for T1-3N0M0 gastric
      cancer were divided into three groups according to digestive tract reconstruction
      techniques, which included Billroth I group (n=30), Billroth II group (n=25) and
      Roux-en-Y group(n=26). Plasma ghrelin level was determined by radioimmunoassay
      preoperatively and one day, one week, half a year, and one year after
      gastrectomy. BMI was similarly recorded. RESULTS: Plasma ghrelin levels of three
      groups decreased sharply to nadir one day after operation, which were (34.2+/
      5.2)%, (37.7+/-4.7)% and (36.5+/-4.9)% respectively. A week after operation they
      were (52.6+/-6.5)%, (48.3+/-5.7)% and (48.1+/-6.0)%. There were no statistical
      difference between groups (P=0.075). Half a year postoperatively, they were
      (91.7+/-7.5)%, (80.4+/-8.1)% and (75.3+/-8.3)% and a year postoperatively(95.3+/
      5.1)%, (84.5+/-6.3)% and (79.9+/-6.7)%, showing that Billroth I group was
      obviously higher than the other two groups (P<0.01) and Billroth II group was
      higher than Roux-en-Y group (P<0.05). BMI of three groups at a year after surgery
      descended by (2.1+/-1.1)%, (4.5+/-1.9)% and (5.7+/-1.8)% respectively,
      demonstrating statistical difference. Linear regression correlation existed in
      the three groups between decreasing amplitude of ghrelin and BMI (P<0.01).
      CONCLUSIONS: Billroth I digestive tract reconstruction takes on the normal
      anatomy and physiology and therefore promotes compensatory ghrelin secretion.
      Falling of ghrelin level greatly contributes to the weight loss after subtotal
      gastrectomy.

PMID- 21713702
TI  - [Quality of life in patients with esophageal carcinoma undergoing thoracoscopic
      and laparoscopic esophagectomy and circular stapled cervical esophagogastric
      anastomosis via retrosternal route].
AB  - OBJECTIVE: To evaluate the quality of life (QOL) in patients with esophageal
      carcinoma after thoracoscopic and laparoscopic esophagectomy and circular stapled
      cervical esophagogastric anastomosis via retrosternal route or three-incision
      open surgery. METHODS: A total of 63 patients with middle-upper esophageal
      carcinoma who underwent radical surgical resection from January 2009 to October
      2010 were enrolled in this study. Thirty-three patients underwent combined
      laparoscopic and thoracoscopic surgery and 30 three-incision open surgery. The
      EORTC questionnaire QLQ-C30 and QLQ-OES18 were used to evaluate the QOL. RESULTS:
      There were no significant differences in the clinical data between the two groups
      except for anastomosis method(P>0.05). In the endoscopy group, there was one
      patient developed anastomotic leakage(3.0%, 1/33), 1 postoperative wound
      infection in the neck (3.0%, 1/33), and 1 anastomotic stricture(3.0%, 1/33). In
      the open group, 8 patients had anastomotic leakage (26.7%, 8/30), 2 had
      anastomotic stricture (6.7%, 2/30), 1 had wound infection in the neck (3.3%,
      1/30), and 6 had pulmonary infection (20.0%, 6/30). All the complications were
      managed by conservative treatment. The two groups differed in dysphagia, food
      intake, pain, obstruction, dyspnea, anorexia, fatigue, financial condition,
      physical function, role function, emotional function, cognitive function, social
      function and global health level and were more favorable in the endoscopy
      group(P<0.05), while there were no significant differences in the other
      dimensions. CONCLUSIONS: The postoperative complication rate is low after
      thoracoscopic and laparoscopic esophagectomy. Stapled anastomosis is associated
      with lower rate of anastomotic leak. QOL is better in patients following
      thoracoscopic and laparoscopic esophagectomy as compared to those following three
      incision open surgery.

PMID- 21713703
TI  - [Adjuvant chemotherapy for gastric cancer: more drugs do not mean better
      efficacy].
AB  - OBJECTIVE: To compare oncologic outcomes between doublet and triplet adjuvant
      chemotherapy for gastric cancer patients undergoing radical resection. METHODS:
      Patients with gastric cancer receiving adjuvant chemotherapy after radical
      resection from January 2004 to December 2008 were included. Doublet was defined
      as 5-FU 750 mg/m2 (days 1-5) or capecitabine 1000 mg/m2 (days 1-14) plus
      cisplatin 60 mg/m2 (day 1) or oxaliplatin 130 mg/m2 (day 1), while triplets had
      epirubicin 50 mg/m2 (day 1) added. Chemotherapy was initiated 4-6 weeks after
      surgery, repeated every three weeks for 6 cycles. Patients were followed-up in
      the outpatient clinic until death or the most recent follow up(April 30, 2010).
      Cox proportional- hazard model and Chi-square test were used to test statistical
      difference. RESULTS: A total of 316 patients (210 received doublets, 106 received
      triplets) had a median follow-up time of 47 months. Seventy-seven patients died
      at the end of the follow-up. Two groups were comparable except for age (median
      age of 57 in doublets, 51 in triplets, P<0.01). The two groups had similar
      disease-free survival (16 months vs. 23 months, P=0.656) and 3-year overall
      survival(59.6% vs. 64.8%, P=0.293). There was no significant difference in severe
      adverse side effects between the two groups (21.9% vs. 30.2%, P=0.107).
      CONCLUSION: Triplet adjuvant chemotherapy appears not to be associated with
      superior efficacy than doublet regimen for patients with gastric cancer after
      radical resection.

PMID- 21713704
TI  - [Effect of early enteral nutrition supplemented with glutamine on postoperative
      intestinal mucosal barrier function in patients with gastric carcinoma].
AB  - OBJECTIVE: To investigate the effect of early enteral nutrition (EEN)
      supplemented with glutamine on postoperative intestinal mucosal barrier function
      of patients with gastric carcinoma. METHODS: Eighty patients with gastric
      carcinoma who underwent intraoperative peritoneal hyperthermic chemotherapy(IPHC)
      were randomized into two groups: EEN+glutamine (EEN+Gln) group(n=40) and EEN
      group(n=40). Intestinal mucosal barrier function was evaluated by serum diamine
      oxidase (DAO), ratio of lactulose to mannitol(L/M), endotoxin
      lipopolysaccharides(LPS), and tumor necrosis factor-alpha(TNF-alpha) at 1 day
      before operation, 1 day, 7 days, 12 days after operation. Time to first flatus
      and tolerance to EEN were recorded as well. RESULTS: There were no significant
      differences in the two groups in demographics(all P>0.05). Two cases(5%) in the
      EEN+Gln group and 1 case (2.5%) in the EEN group could not tolerate well(P>0.05).
      On postoperative day 1, there were no differences in serum DAO, L/M ratio, LPS,
      TNF-alpha between the two groups (P>0.05). On postoperative day 7, all the
      parameters for mucosal barrier function were significantly lower in the EEN+Gln
      group. On postoperative day 12, the urinary L/M and DAO, LPS, and TNF-alpha were
      still significantly lower in the EEN+Gln group, however, urinary L/M was
      comparable between the two groups. There were no differences between the two
      groups in the time to first flatus (P>0.05). CONCLUSION: The immunologic
      tolerance of enteral nutrition supplemented with glutamine is favorable, which
      provides protective effect on intestinal mucosal barrier in patients with gastric
      carcinoma undergoing IPHC.

PMID- 21713705
TI  - [Laparoscopic total mesorectal excision combined with intersphincteric resection
      for ultra-low rectal cancer].
AB  - OBJECTIVE: To evaluate clinical outcomes after laparoscopic total mesorectal
      excision (TME) combined with intersphincteric resection (ISR) for ultra-low
      rectal tumors. METHODS: Clinical data of 36 patients with ultra-low rectal tumor
      undergoing laparoscopic TME combined with ISR were analyzed retrospectively.
      RESULTS: The median distance from the inferior margin of the tumor to the anal
      verge was 3.4 (2.0-5.0) cm. There were 33 cases of well/moderately differentiated
      adenocarcinoma and 3 rectal malignant villous adenoma. There were 16 patients
      with stage I disease, 15 with stage II A, 3 with stage III A, and 1 with III B.
      Postoperatively, one patient developed stenosis at the end ileostomy and 3
      anastomotic leakage. After a median follow-up of 16(4-49) months, one patient
      developed local recurrence at the anastomosis and one case died of liver
      metastasis. In the 19 patients who had a minimum follow-up of one year, the bowel
      movements frequency ranged from 1-4 times per day, and these patients were able
      to withhold defecation for more than 5 minutes. CONCLUSIONS: Laparoscopic TME
      combined with ISR can achieve oncologic clearance, sphincter preservation, and
      minimal invasiveness for ultra-lower rectal cancer. However, patients selection
      should be cautious.

PMID- 21713706
TI  - [Expression and clinical significance of GINS complex in colorectal cancer].
AB  - OBJECTIVE: To investigate the expression and clinical significance of GINS
      complex in colorectal cancer (CRC). METHODS: The expression level of GINS complex
      including PSF1, PSF2, PSF3 and SLD5 in CRC specimens (n=76) were detected by real
      time fluorescent quantitative polymerase chain reaction. The association of GINS
      complex with clinicopathological parameters and prognosis of CRC patients were
      analyzed. RESULTS: The relative expression level of PSF1, PSF2, PSF3, and SLD5
      mRNA in CRC tissues was 0.001 853+/-0.000 651, 0.007 757+/-0.004 260, 0.000 967+/
      0.000 481 and 0.003 248+/-0.001 721, which was significantly higher than that in
      normal colorectal mucosa tissues (0.000 352+/-0.000 169, 0.002 951+/-0.001 216,
      0.000 472+/-0.000 271, and 0.001 675+/-0.001 156) (all P<0.01). PSF1 mRNA
      expression was associated with tumor size (P<0.01), and PSF2 mRNA expression with
      age (P<0.05) and lymph node metastasis (P<0.05). No correlations between PSF3
      mRNA expression and clinicopathological parameters were observed. SLD5 mRNA
      expression was associated with lymph node metastasis (P<0.01). Patients with high
      expression of PSF1, PSF2 and SLD5 had worse 5-year overall survival rate (57.1%,
      54.3%, and 54.3%) than those with low expression (77.1%, 80.0%, and 80.0%) (all
      P<0.05). Multivariable Cox regression analysis indicated that PSF1 mRNA
      expression (P<0.05) was an independent factor associated with prognosis of
      colorectal cancer. CONCLUSIONS: Overexpression of GINS complex in CRC is
      associated with clinicopathological characteristics and prognosis of colorectal
      cancer. PSF1 expression is prognostic for CRC patients.

PMID- 21713707
TI  - [Expression and clinical significance of COX-2 and BCL-2 in distal transitional
      mucosa adjacent to rectal carcinoma].
AB  - OBJECTIVE: To investigate the expression of COX-2 and BCL-2 in transitional
      mucosa adjacent to rectal carcinoma, and to determine whether precursor event
      exists in the transitional mucosa. METHODS: Mucin histochemical method (HID/AB)
      was used to determine the distal mucosa 2 cm away from rectal carcinoma in 54
      patients with rectal cancer. Immunohistochemical method was employed to detect
      the expression of BCL-2 and COX-2 in the rectal cancer specimen, transitional
      mucosa (TM), non-transitional mucosa (NTM), and 20 cases of normal rectal mucosa.
      Student's t-test and Chi-square test were preformed. RESULTS: Nineteen patients
      with positive TM were found. COX-2 expression was identified in 81.5% of cancer
      tissue, 21.1% of TM, 17.1% of NTM, and 10.0% in normal mucosa. BCL-2 protein was
      found in 77.8% of cancer tissue, 21.1% of TM, 22.9% of NTM, and 5.0% of normal
      mucosa. The expressions of COX-2 and BCL-2 in TM were significantly different
      from tumor tissue[(0.737+/-0.895) versus (3.519+/-1.998), and (0.632+/-0.955)
      versus (2.833+/-1.756), all P<0.01]. However, there were no significant
      differences between TM and NTM or normal mucosa. CONCLUSIONS: Expressions of COX
      2 and BCL-2 are non-specific in the transitional mucosa at the distal rectum.
      Evidence is not available in TM being precursor lesion.

PMID- 21713708
TI  - [Factors associated with incontinence following anorectal procedures].
AB  - OBJECTIVE: To investigate the factors associated with postoperative fecal
      incontinence after anorectal procedures. METHODS: A total of 1074 patients
      underwent anorectal procedures in the Department of Colorectal Surgery at the
      Coloproctology Hospital of Shenyang. Factors associated with postoperative fecal
      incontinence were analyzed retrospectively. RESULTS: Follow-up was available in
      all the patients. One hundred and forty-four(13.4%) patients developed mild
      incontinence, and 57(5.3%) moderate incontinence. There was no complete
      incontinence. The overall incontinence rate was 18.7%. The incontinence rate was
      41.8%(107/256) after fistula procedures, higher than that after hemorrhoid
      procedures(12.4%,73/591) and fissure procedures(9.2%,21/227), and the differences
      were statistically significant (P<0.01). Among 490 patients who received
      injection therapy for internal hemorrhoids, patients who received 10 ml of
      Xiaozhiling or more had a mild incontinence rate of 10.4%(27/259) and a moderate
      incontinence rate of 2.3%(6/259), and in those who received less than 10 ml of
      Xiaozhiling, the mild incontinence rate was 9.5%(22/231) and moderate
      incontinence rate was 4.3%(10/231). The differences were not statistically
      significant (all P>0.05). In 354 patients who underwent hemorrhoidectomy, the
      mild incontinence rate and moderate incontinence rate were both 14.1% in those
      who had excision of 3 or more hemorrhoids, and were 3.9%(11/283) and 2.1% (6/283)
      in those who had excision of less than 3 hemorrhoids, and the differences were
      statistically significant (P<0.01). There was no difference in Incontinence rate
      was not associate with fistula or fissure procedure (P>0.05). CONCLUSIONS: The
      incidence of incontinence is high after fistula procedures. Excision of
      hemorrhoids should not exceed 3 hemorrhoids. Wider adoption of injection therapy
      is encouraged.

PMID- 21713709
TI  - [Effect of the expression of ghrelin receptors on the postoperative underpowered
      small intestinal motility in rats].
AB  - OBJECTIVE: To investigate the effect of the expression of ghrelin receptors on
      the postoperative small intestine dysmotility in rat models. METHODS: The effect
      of different concentrations of ghrelin (0, 0.01, 0.1, 0.5, 1.0 MUmol/L) on the
      contraction of smooth muscle strips of rat small intestine in the presence or
      absence of carbachol was observed in vitro. End-to-side anastomosis was performed
      in the study group and sham controls were used. The expression of ghrelin
      receptors(GHS-R1a) in small intestine muscle layers was detected by
      immunohistochemistry and Western blot. RESULTS: In vitro, ghrelin enhanced the
      contraction of smooth muscle strips in the presence of carbachol, and the
      differences in contraction induced by different concentrations of ghrelin(0.1,
      0.5, 1.0 MUmol/L) were statistically significant [(223+/-18)%, (245+/-22)%,
      (264+/-25)%, P<0.01]. Immunohistochemistry study showed that GHS-R1a mainly
      located in the muscular layer of the bowel wall. The expression of GHS-R1a in the
      circular and longitudinal muscle was significantly weaker than that in the
      control group. The expression of ghrelin receptors after surgery was down
      regulated in the study group, which was lower than that in the control
      group(0.51+/-0.02 vs. 0.71+/-0.01, P<0.01). CONCLUSION: Down regulation of
      ghrelin receptors in small intestine muscle layers may contribute to the
      occurrence of small intestine dysmotility after intestinal surgery.

PMID- 21713710
TI  - [Expression of aquaporin 3, 4, and 8 in colonic mucosa of rat models with slow
      transit constipation].
AB  - OBJECTIVE: To investigate the expression of aquaporin 3, 4, and 8 in the colonic
      mucosa of rat models with slow transit constipation (STC). METHODS: STC rat model
      was established by giving the rats the compound solution of diphenoxylate. Real
      time polymerase chain reaction (RT-PCR) was used to measure the expression of
      aquaporin mRNA in colonic mucosa of STC rat models (study group,n=16) and normal
      rats (control group,n=16). Gray scale ratio of aquaporin to beta-action (internal
      reference) was used for quantification. RESULTS: RT-PCR revealed that the mean
      gray scale ratios of aquaporin 3 in the proximal colon of the study group and
      control group were 0.344 and 0.602 (P<0.05), and were 0.419 and 0.509 in the
      distal colon (P>0.05), respectively. The mean gray scale ratios of aquaporin 4 in
      the proximal and the distal colon were 0.764 and 0.759 in the study group
      (P>0.05), and were 0.776 and 0.736 in the control group (P>0.05), respectively.
      However, there was no expression of aquaporin 8 in the proximal and the distal
      colon in either the study group or the control groups. CONCLUSIONS: Expression of
      aquaporin 3 in the proximal colon of STC rat models is down-regulated, which
      regulates water absorption. There are no significant changes in the expressions
      of aquaporin 4 and 8.

PMID- 21713711
TI  - [Comparison of short-term postoperative outcomes between hand-assisted
      laparoscopic and conventional sigmoidectomy].
AB  - OBJECTIVE: To compare the safety and efficacy perioperatively between hand
      assisted laparoscopic surgery (HALS) and conventional open sigmoidectomy.
      METHODS: Prospectively collected data on 115 patients with sigmoid colon cancer
      between January 2009 to June 2010 were analyzed. There were 62 patients in the
      HALS group and 53 in the conventional sigmoidectomy group (CS). Patient
      characteristics, operative parameters, and perioperative outcomes were compared.
      RESULTS: HALS patients were similar to CS patients in age(60.2 yrs vs. 63.4 yrs,
      P=0.163), gender (53.2% vs. 60.4% male, P=0.441), tumor size (4.7 cm vs. 5.3 cm,
      P=0.114) and tumor stage. The two groups were comparable in operative time
      [(122.4+/-32.0) min vs.(126.7+/-37.4) min, P=0.510], lymph node harvest (15.1+/
      4.6 vs. 16.8+/-6.4, P=0.163), free margin length [(4.1+/-1.8) cm vs.(4.3+/-1.7)
      cm, P=0.601], and postoperative complications. However, HALS group had less
      intraoperative bleeding [(62.6+/-35.4) ml vs. (168.9+/-137.1) ml, P=0.000],
      shorter time to flatus [(2.3+/-0.8) d vs. (3.3+/-1.1) d, P=0.000], and shorter
      hospital stay [(8.8+/-2.7) d vs.(12.6+/-8.0) d, P=0.001]. CONCLUSIONS: HALS
      results in similar short-term outcomes compared to conventional surgery. HALS is
      safe and minimally invasive.

PMID- 21713714
TI  - [Planning and intraoperative controls in rhinoplasty].
AB  - We present a technique to quantify computer simulation in rhinoplasty and to make
      individual templates to be used intraoperatively. With these templates the exact
      position and shape of the nasal dorsum, tip, columella and anterioar nasal spine
      can be controlled and adjusted. Due to our experience this techniques contributes
      to precise surgical outcome and patient's satisfaction.

PMID- 21713715
TI  - [Fusobacterium necrophorum--cause of a mastoiditis with skull- and mandibular
      joint osteomyelitis].
AB  - BACKGROUND: The typical clinical manifestation of an infection with the obligate
      anaerobic, gram-negative, rod-shaped bacteria Fusobacterium necrophorum is the
      Lemierre syndrome. As the cause of osteomyelitis and mastoiditis factors of the
      normal bacteria flora are more likely to be found than Fusobacterium necrophorum.
      Nevertheless, Necrobacillosis is an important differential diagnosis of
      complicated courses of mastoiditis. MATERIAL AND METHODS: Because the clinical
      courses of mastoiditis with osteomyelitis may differ a lot, making the
      appropriate diagnosis more difficult, consistently and flawless detection of the
      pathogens is important. Therefore a correct specimen collection, transportation
      and the subsequent cultivation of the pathogens is essential. RESULTS: The genus
      Fusobacterium is an obligate anaerobic, gram-negative rod-shaped bacteria.
      Infections involving the genus Fusobacterium are usually formed endogenously.
      They are characterized by subacute to chronic, purulent gangrenous necrotizing
      inflammations. CONCLUSION: As a differential diagnosis, infections with
      Streptococcus spp., Haemophilus influenzae, Branhamella catarrhalis and
      Staphylococcus aureus are more likely to cause mastoiditis and osteomyelitis than
      an infection with Fusobacterium necrophorum. However, the infection with this
      fusiform bacillus is possible under pathological circumstances e.g. deficiency
      syndroms, so that when observing a prolonged disease course of mastoiditis an
      infection with Fusobacterium necrophorum should be considered .

PMID- 21713717
TI  - [Hand hygiene: basic, but not trivial].
AB  - Hand hygiene is considered as the pillar of infection control and prevention.
      Healthcare-associated infections have a great impact on morbidity, length of
      hospital stay, and treatment costs. Hand disinfection is considered to be the
      single most effective tool to prevent healthcare-associated infections and cross
      transmission of multi-drug resistant bacteria. The WHO defined "5 moments" for
      hand hygiene and highlighted the need for new strategies to improve everyday hand
      hygiene practices on the basis of the current low compliance. Reasons for non
      compliance are multifaceted and behavioural, religious, and sociocultural aspects
      have to be considered when designing intervention programs. Despite all these
      barriers it is worth the effort to aim at quality of care improvement.

PMID- 21713718
TI  - [How many hospital insurance claims are based on infection control failures?].
AB  - BACKGROUND AND OBJECTIVE: It can be expected that hospital insurance claims based
      on health care-associated infections (HCAI) will increase in German hospitals
      because of growing media and patient interest in this topic. It was the aim of
      this study to determine the percentage of insurance claims because of HCAI among
      all potential cases of avoidable HCAI. METHODS: Data of a core group of 254
      hospitals continuously working with one of the largest German hospital insurance
      companies (ECCLESIA) over an eleven-year period were used. The observed number of
      cases caused by infection control failures (ICF) was compared with the potential
      number of avoidable HCAI in the entire patient group treated in these hospitals.
      The type of the failure as well as the probability of an actual ICF were
      evaluated in each case of ICF by a team of experts. RESULTS: A hospital insurance
      claim was made in only 0.2 % of all avoidable HCAI cases. Among the 117 cases
      with payments exceding 700 Euro, only 39 were found to have had a specific
      infection control problem. Fewer than half of these cases were considered as
      probable infection control failures by the experts in this field. CONCLUSION:
      Hospital insurance claims because of HCAI are still rare in German hospitals. In
      the group of insurance claims because of ICF, some cases had been classified
      incorrectly.

PMID- 21713719
TI  - [Assessment of drug treatment in geriatrics with the new FORTA criteria].
AB  - BACKGROUND: Multimorbidity in the elderly often leads to inappropriate and
      harmful polypharmacy. Various approaches have been used to prioritize components
      of drug treatment, especially as on negative lists like the Beers list. A new
      approach is the FORTA assessments system ( Fit f OR The Aged) in which drugs are
      graded as positive (A, should be given), intermediate (B or C), and negative (D
      should not be given). METHODS: In this pilot study of 46 patients in a geriatric
      ward medication was assessed on admission and at discharge, using the FORTA
      criteria. All changes in the number of prescribed drugs, the distribution of
      FORTA criteria, and the number of drug interactions were recorded. RESULTS: The
      use of FORTA resulted in a decrease in the total number of prescirbed drugs from
      7.3 +/- 2,9 to 6.7 +/- 2,3 (p = 0.06), and an increase in positively assessed
      drugs (A / B) from 59 +/- 20 to 77 +/- 38 % (p < 0.01), as well as a decrease in
      negatively assessed drugs (D) from 7 +/- 12 to 5 +/- 9 % (p = 0.06). The number
      of drugs assessed as intermediate (C) did not change significantly. Under
      treatment decreased from 65 to 39 % (p < 0.01), over-treatment from 65 % to 20 %
      (p < 0.01). The number of drug interactions decreased from 79 to 54 (p < 0.01).
      CONCLUSION: This uncontrolled pilot study indicates that the FORTA criteria can
      be used in day-to-day clinical care: it describes the quality of changes in drug
      treatment in a geriatric ward in a plausible way. This study has provided basic
      uncontrolled data which should be validated in controlled studies comparing the
      quality of treatment with or without the use of the FORTA criteria. (DKRS-ID:
      DRKS00000531).

PMID- 21713720
TI  - [Acute squamous cell carcinoma of the gallbladder: a rare cause of acute
      cholecystitis].
AB  - HISTORY AND ADMISSION FINDINGS: A 54-year-old woman with signs of acute
      cholecystitis but no other relevant diseases was admitted into our hospital.
      INVESTIGATIONS: The abdominal ultrasonography showed an acute cholecystitis with
      possibly an abscess in the bed of the gallbladder (DD gall bladder cancer).
      Therefore a laparoscopy was performed which revealed a tumorous infiltrating the
      adjacent organs. A R1 resection was performed. DIAGNOSIS, TREATMENT AND COURSE:
      The histological examination revealed the rare finding of a squamous cell cancer
      of the gall bladder. On advice of our tumor board, chemotherapy with cisplatin
      and 5-flourouracil was initiated. Tumor-associated bile duct stenosis required
      endoscopic stent implantation. Despite the poor prognosis the disease remained
      stable 18 month later, with a Karnofsky index of 100 %. CONCLUSION: Squamous cell
      carcinoma of the gallbladder is rare and requires a good interdisciplinary
      management. In an individual setting it is possible to increase survival with
      interdisciplinary treatment and palliative chemotherapy.

PMID- 21713721
TI  - [Diagnosis and treatment of pneumocystis jirovecii pneumonia].

PMID- 21713722
TI  - [ADP receptor blockers: new insights in the therapy and prophylaxis of ischemic
      heart disease].
AB  - Adenosine diphosphate (ADP)-induced platelet activation plays a pivotal role in
      the thrombocyte aggregation and pathogenesis of ischemic heart disease. The long
      term benefit of dual anti-platelet therapy with ADP-receptor antagonists, such as
      clopidogrel, in combination with aspirin is well established for patients
      following coronary stent implantation. This review discusses latest developments
      in the field of ADP-receptor antagonists.

PMID- 21713723
TI  - [Why history of medicine should remain part of the medical curriculum].

PMID- 21713725
TI  - [Risk adapted treatment of osteoporosis].

PMID- 21713726
TI  - [Proximal ulna fractures].
AB  - Proximal ulna fractures are common injuries in the upper extremity. The severity
      of injury ranges from isolated olecranon fractures to complex elbow fracture
      dislocations. Relevant anatomic features of the proximal ulna for fracture
      management are presented in the first part of this article. Furthermore, standard
      and recent techniques of surgical treatment are described in detail for olecranon
      and Monteggia fractures as well as for fractures of the coronoid process.
      Functional outcome and complications of fracture treatment are discussed.

PMID- 21713727
TI  - Complex technique of large sural flap: an alternative option for free flap in
      large defect of the traumatized foot.
AB  - The distally based sural fasciocutaneous flap has become a main part of the
      reconstruction of the lower leg, heel and foot. However, perfusion problems and
      venous congestion have been reported. Over the past decade, several flap
      modifications have been reported to improve flap viability and to solve a myriad
      of reconstructive needs. The purpose of this paper is to describe our experience
      in harvesting the reversed large sural flap from the proximal and middle third of
      the leg for large defects on the foot. We applied the extended reversed sural
      flap from the proximal third of the leg in traumatized patients which had large
      defects on their foot. The technique was done in 3 parts: 1- the flaps were
      designed in the proximal third of the leg five centimeter lipofascial tissue was
      protected around the pedicle in distal part; 3- The pivot point was located in
      seven to eight cm proximal the lateral malleolus before the first fasciocutaneous
      perforators arising from the peroneal artery. Sural flaps from the proximal and
      middle third of the leg were designed in13 patients who had large defects on
      their foot. No flap necrosis or split thickness skin graft loss occurred. The
      flaps healed by the 3rd week excluding two patients. This study supports the
      application of our technique as a safe, easy and useable method in large defects
      of the foot. The results showed low rates of ischemia, venous congestion,
      dehiscence, infection and flap necrosis. Proximal extended and large distally
      based sural flap is an alternative to free tissue transfer for large defect
      reconstruction of the foot.

PMID- 21713728
TI  - Bonfils fiberscope: intubating conditions and hemodynamic changes without
      neuromuscular blockade.
AB  - To compare intubating conditions and hemodynamic changes between Bonfils
      Intubation Fiberscope and Macintosh laryngoscopy without administering
      neuromuscular blocking drugs (NMBDs). METHODS: In this randomized controlled
      trial,80 male and female patients, scheduled for elective surgery, aged 15 to 60
      years, ASA class II or I, non-obese, non smokers, without anticipated difficult
      intubation; were randomly allocated into two groups of 40: Bonfils and Macintosh.
      Following adequate hydration and preoxygenation, midazolam 0.03 mg.kg(-1) was
      administered, followed by intravenous alfentanil 20 ug.kg(-1), lidocaine 1.0
      mg.kg(-1), and propofol 2 mg.kg(-1) sequentially. Trachea was then intubated
      using Bonfils Intubation Fiberscope in the Bonfils group and conventional
      Macintosh laryngoscopy in the Macintosh group. Intubating condition, mean
      arterial blood pressure, heart rate, pulse oximetry, and success rate were
      measured. RESULTS: Clinically acceptable intubating condition scores did not
      differ significantly between the groups (P=0.465). Compared to the baseline
      values, heart rate rose significantly after intubation only in the Macintosh
      group (P<0.001). Although mean arterial blood pressure increased immediately
      after intubation in the Macintosh group (P=0.022), its post-intubation values
      were significantly less than baseline in both groups (P<0.001). Intubation time
      took much longer in the Bonfils group (40 s) than the Macintosh group (11 s),
      P<0.001. In the absence of NMBDs, Bonfils Intubation Fiberscope compares well
      with Macintosh laryngoscopy in terms of success rate and intubating conditions,
      but with less mechanical stress and hemodynamic compromise and longer intubation
      time.

PMID- 21713729
TI  - Comparing the efficacy of prophylactic p6 acupressure, ondansetron,
      metoclopramide and placebo in the prevention of vomiting and nausea after
      strabismus surgery.
AB  - To compare the efficacy of acupressure wrist bands, ondansetron, metoclopramide
      and placebo in the prevention of vomiting and nausea after strabismus surgery.
      Two hundred patients, ASA physical status I or II, aged between 10 and 60 years,
      undergoing strabismus surgery in Farabi Hospital in 2007-2008 years, were
      included in this randomized, prospective, double-blind and placebo-controlled
      study. Group I was the Control, group II received metoclopramide 0.2 mg/kg, group
      III received ondansetron 0.15 mg/kg iv just before induction, in Group IV
      acupressure wristbands were applied at the P6 points. Acupressure wrist bands
      were placed inappropriately in Groups I, II and III. The acupressure wrist bands
      were applied 30 min prior to the induction of anesthesia and removed six hours
      after surgery. Postoperative nausea and vomiting (PONV) was evaluated within 0-2
      hours and 2-24 hours after surgery by a blinded observer. Results were analyzed
      by X(2) test. A P value of < 0.05 was taken as significant. The incidence of PONV
      was not significantly different in acupressure, metoclopramide and ondansetron
      during the 24 hours. Acupressure at P6 causes a significant reduction in the
      incidence of PONV 24 hours after strabismus surgery as well as metoclopramide 0.2
      mg/kg and ondansetron 0.15 mg/kg iv for patients aged 10 or more.

PMID- 21713730
TI  - Seroprevalence of toxoplasmosis in HIV(+)/AIDS patients in Iran.
AB  - Toxoplasma gondii has arisen as an important opportunistic agent especially in
      the central nervous system and in advanced HIV disease can cause significant
      morbidity and mortality. This study was carried out to determine the
      seroprevalence of toxoplasmosis among HIV-positive patients in Iran. Blood
      samples were collected from 201 HIV-positive patients and anti-toxoplasma
      antibodies were detected by using conventional ELISA. An antibody titer of >3
      IU/ml was considered positive. The majority of studied patients were male (male
      to female ratio: 5 to 1) with the mean age of 36 +/- 1 yrs. The seroprevalence of
      toxoplasmosis in HIV-positive patients was 49.75%. The mean CD4 count in HIV
      patients with positive toxoplasma serology was 332.5 +/- 22.4 cells/ul. Only 1%
      of the patients had IgM anti-toxoplasma antibodies and 10% of the patients had
      clinical toxoplasma encephalitis. The mean CD4 count in this group was 66.4 +/-
      15.5 cells/ul and there was a significant association between CD4 count and rate
      of toxoplasma encephalitis (P<0.001). Previous reports suggested that toxoplasma
      encephalitis could be prevented by appropriate chemoprophylaxis. In view of the
      relatively high prevalence of toxoplasma infection found among the HIV-infected
      patients in our study, we suggest that routine screening for toxoplasma should be
      undertaken for all HIV-infected patients in Iran.

PMID- 21713731
TI  - Clinical characteristics and the prognosis of childhood rhabdomyosarcoma in 60
      patients treated at a single institute.
AB  - Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children. The
      aim of study was to retrospectively review the treatment results of childhood
      rhabdomyosarcoma and identify prognostic factors. 60 children with
      rhabdomyosarcoma treated between 1996 and 2002 in Shafa Hospital were reviewed.
      The data were analyzed for clinico-epidemiological factors. Age, gender, race,
      histology type, primary site, tumor size and intergroup rhabdomyosarcoma study
      (IRS) group were evaluated. The primary site of involvement was orbit in 6 cases
      (10%) head and neck nonparameningial in 12 cases (20%), parameningial region in
      12 cases (20%). The histological findings were as follows: 12 cases (72.5%) for
      embryonal, 6 cases (10%) for alveolar and 11 cases (17. 5%) for botryoid type.
      With respect to the IRS III (15%) were group II, 32 (52.5%) were group III and 24
      cases (40%) were group IV. The 5-year survival rate was 47.9%. Primary tumor site
      (P=0.0003), and histology (P=0.05) were associated significantly with survival
      after recurrence. Among the variables, age, gender, regional lymph node
      involvement, and IRS group did not affect 5-year survival but the type and time
      of recurrence (P=0.0002), and its relation with therapy (P=0.0001) were
      associated with survival. This study showed that overall survival for
      rhabdomyosarcoma is dependent on histological subtype, primary site, disease
      group, duration of disease before treatment. The outcome for infant with RMS is
      less satisfactory than older children and the patients aged 1-9 years had the
      best 5 year survival.

PMID- 21713732
TI  - Temperature changes during and after eccentric contractions and its effect on
      force and desmin loss in rat.
AB  - The typical features of eccentric exercise-induced muscle damage is prolonged
      loss of muscle strength and the most rapid structural change in the fibers is
      loss of immunostaining for the intermediate filament protein, desmin. In this
      study isolated perfused rat muscle was used to examine the direct effect of
      temperature changes on the eccentric contraction-induced force and desmin loss.
      The left medial gastrocnemius muscle was separated and the entire lower limb was
      transferred into a prewarmed (35 degrees C) organ bath. Temperature was adjusted
      to 31 or 39 degrees C during and after eccentric contractions. Maximal isometric
      force and desmin loss were measured after 15 isometric or eccentric contractions.
      According to our data, organ bath temperature changes during or after eccentric
      contractions had no significant effect on force loss. However, a strong
      correlation between desmin loss and temperature changes during (r = 0.886, P<
      0.05) and a weak correlation between desmin loss and temperature changes after
      (r= 0.699, P<0.05) eccentric contractions was observed. Our results suggest that
      cooling during eccentric contractions may decrease desmin loss but temperature
      changes after eccentric contractions have no effect on desmin loss.

PMID- 21713733
TI  - Pulmonary complications of mustard gas exposure: a study on cadavers.
AB  - Sulfur mustard gas is one of the chemical warfare gases that roughly about 45000
      soldiers continue to suffer long-lasting consequences of exposure during the Iran
      Iraq war between 1980 and 1988. According to the common pulmonary lesions due to
      this gas exposure, we studied gross and microscopic pulmonary lesions in cadavers
      and also assessed the main causes of mortality caused by mustard gas exposure. A
      case-series study was performed on hospital record files of 100 cadavers that
      were exposed with documented sulfur mustard gas during the Iran-Iraq war from
      1979 to 1988 and autopsied in legal medicine organization In Tehran between 2005
      and 2007 and gross and microscopic pathological findings of autopsied organs such
      as hematological, pulmonary, hepatic, and renal changes were evaluated. All cases
      were male with the mean age of 43 years. The time interval between the gas
      exposure and death was almost 20years. The most frequent pulmonary complication
      was chronic bronchitis in 81% of autopsied cadavers. Other pulmonary findings
      were progressive pulmonary fibrosis (9%), pulmonary infections and tuberculosis
      (29%), malignant cellular infiltration (4%), and aspergilloma (1%). According to
      the chronic progressive lesions caused by mustard gas exposure such as pulmonary
      lesions and also its high mortality rate, suitable programming for protection of
      the gas exposed persons and prohibiting chemical warfare are recommended.

PMID- 21713734
TI  - Anatomy of arterial supply of the soleus muscle.
AB  - Soft tissue defects of the lower limb are a challenge to the plastic surgeon but
      a soleus muscle flap often provides the solution. Various types of soleus muscle
      flap have been described, based mainly on the vascular supply. This study has
      been conducted as a descriptive study. The arterial blood supply of the soleus
      muscle was studied in 45 cadaveric lower limbs. The blood vessels and their
      branches to the muscle were dissected. The mean length of the soleus muscle was
      37 +/- 2.2 Cm. In 66.7% of the limbs at least two branches arose from the
      popliteal artery trunk. The average distance of the first branch was 2.61 +/-
      1.75 Cm distal to the fibular head. And the second branch was 3.88 +/- 0.7 Cm
      distal to the fibular head. The average number of branches to the soleus muscle
      from the posterior tibial trunk was 4.3 +/- 0.7. The average distance of the
      first branch was 9.4 +/- 2.3 Cm from medial malleolus and second branch was 15 +/
      3.4 Cm. The average number of branches to soleus arising from the proneal artery
      was 3.8 +/- 0.8. The proneal artery gave 2-5 branches to the soleus muscle in the
      limbs that in 95.6% of the limbs were found three branches from proneal artery
      trunk to soleus muscle. In this study have been shown, the distribution of the
      arteries entering the soleus muscle and how the information may be used in the
      design of soleus muscle flaps. However, clinical application of distal pedicle
      soleus muscle flaps in Iranian population is not beneficial and we do not
      recommend it to the surgeons.

PMID- 21713735
TI  - Effect of cryoanalgesia on post-thoracotomy pain.
AB  - We prepared this study to determine the effect of cryoanalgesia on post
      thoracotomy pain. In this double-blinded randomized clinical trial, 60 patients
      who underwent thoracotomy were divided into two groups (control and
      cryoanalgesia). Visual Analogue Scale (VAS, 0-10) was used for the measurement of
      severity of post-thoracotomy pain. It was classified into three categories: 0-1
      (mild), 2-3 (moderate), and 4-10 (severe). Pethidine (0.5-1 mg/kg) was
      administered in case of need for both groups. Patients were visited at the
      hospital a week later, and were contacted by phone at the first, second, and
      third months post-operatively. Intensity of pain in the control group was higher
      than the cryoanalgesia group in all visits the follow-up period. On the second
      day, the frequencies of severe pain (4-10) were 33.3% and 0 in the control and
      cryoanalgesia groups, respectively. The mild pain on the seventh day was 13.3%
      and 83.3% in the control and cryoanalgesia groups, respectively (P < 0.01).
      Pethidine consumption was 151.6 +/- 27 mg in the control group and 87.5 +/-48 mg
      in the cryoanalgesia group on the first day post-operation (P < 0.001).
      Cryoanalgesia is a useful technique with not serious side effects in order to
      alleviate post-thoracotomy pain and reduce the need for opiate consumption.

PMID- 21713736
TI  - Can quality of life questionnaires be used in diabetics to assess the relation
      between HbA1c and patients' domain aspects?
AB  - Over the past few decades, quality of life (QOL) has become an important concept
      in medical researches and treatments. Different meaningful reasons are given for
      this development. In the current research two standard questionnaires for
      evaluating of QOL were selected. First one, was a questionnaire from The World
      Health Organization (WHOQOL-BREF 26) and the second one, The Iranian Diabetics'
      Quality of Life (IRDQOL). The goal of this study is to assess the relation
      between different domains of these questionnaires and HbA1c in diabetics. A
      random sample of Iranian adult outpatient diabetics (n=76) was selected and they
      completed the WHOQOL and IRDQOL assessment instruments. In addition HbA1c was
      measured in these patients by calorimetric method. Comparisons were made between
      scores of "questionnaires' domains" and "HbA1c". Data analysis was carried out by
      the use of T-test, Spearman correlation coefficient, Pearson's correlation
      coefficient, and non-parametric statistical methods including Spearman
      correlation coefficient. Data analysis shows Psychological domain score in IRDQOL
      is lower than in WHOQOL and it is significant (P<0.0001). Physical domain score
      in IRDQOL is lower than WHOQOL and it is significant (P<0.0001). In WHOQOL
      questionnaire, analysis data showed when the patient's age increased, physical
      and psychological domain's score decreased. There is probably no relation between
      questionnaire domains and HbA1c in diabetics. Based on the findings in this
      research, there was obviously almost no difference between the two questionnaires
      for checking the QOL, but in IRDQOL spiritual domain is a very unreliable domain.

PMID- 21713737
TI  - Hepatitis-C and hepatitis-B co-infections in patients with human immunodeficiency
      virus in Tehran, Iran.
AB  - We carried out a study to determine the seroprevalence of HBV and HCV infections
      in HIV positive patients at a main referral center for HIV/AIDS in Iran. Serum
      samples from 201 HIV positive patients referring to a referral center for
      HIV/AIDS were analyzed for the presence of some hepatitis B (HBsAg, anti-HBc,
      anti-HBs) and Hepatitis C (anti-HCV) markers, during 2004- 2005. HBsAg was
      positive in 27 patients (13.4%), anti-HBc was positive in 60 patients (29.8%) and
      anti-HBs in 23 patients (11.4%). Anti-HCV Ab was positive in 135 of 201 (67.2%).
      HBV and HCV coinfection was observed in 73 of 201 (36.3%). The maximum prevalence
      of HBV-HIV and HCV-HIV coinfections were seen in intravenous drug users; 61.2%
      and 85.1%, respectively (P<0.0001). The minimum prevalence of HBV-HIV and HCV-HIV
      were seen in HIV patients' wife (HIV(+) patients who were infected by monogamous
      sexual contact with their HIV positive husband) both of them were 8% (P<0.0001).
      This study showed that HBV-HIV and HCV-HIV coinfections are significant in
      patients with HIV/AIDS in Iran. A greater relevance was observed in the
      association between HCV and HIV. This study suggests that it is necessary to
      investigate risk factors and risk groups for these infections in Iran.

PMID- 21713738
TI  - The effect of paroxetine on ouabain-induced toxicity in isolated guinea pig
      atria.
AB  - It has been reported that selective serotonin reuptake inhibitors (SSRIs) possess
      some cardiac effects. In the present study we have investigated the effect of
      paroxetine (PX), a potent SSRI agent, on spontaneously as well as ouabain-induced
      arrhythmia beating isolated guinea-pig atria. The Guinea-pig heart was rapidly
      removed; the auricles were dissected out in oxygenated modified Krebs solution.
      The rate and force of spontaneous contractions were recorded isometrically with a
      photosensitive transducer. PX (1-16 ug/ml) caused a dose-dependent decrease in
      the rate of contractions (14-70%) and contractile force (8-16%). Ouabain alone
      (1.2 ug/ml) produced arrhythmia at 7.2 +/- 1.5 min and asystole at 20.1 +/- 3.1
      min. Pretreatment with PX (4 ug/ml) significantly increased the time of
      arrhythmia onset to 19.8 min. In addition, PX prolonged the duration of action
      beating from 20.1 +/- 3.1 min to 43.1+/- 2.6 and delayed the occurrence of
      asystole. The pattern of contractile force by PX + ouabain treatment was more
      regular than that observed after administration of ouabain alone. The above
      findings may the probably be due to the inhibition of cardiac Na(+) and Ca(2+)
      channels or autonomic nervous system. Results also suggest that PX may reduce the
      membrane conductance through inhibition of ionic channels to prevent ouabain
      induced arrhythmia.

PMID- 21713739
TI  - Primary echinococcus cyst of the thyroid: a case report.
AB  - Echinococcosis, although eradicated in many countries, is still widespread in
      communities where agriculture is dominant. Cystic hydatidosis is a significant
      public health problem in the regions with endemic echinococcosis. The hydatid
      cysts tend to form in the liver or lung, but may also be found in other organs of
      the body such as brain, heart, and bone, while thyroid gland involvement is
      rather rare. A 25 year old male presented with solitaire goiter. Laboratory tests
      and thyroid profile proved normal. Surgical exploration revealed hydatid cyst in
      the left lobe of the thyroid gland. Examination of the nodule showed it to be a
      solitary primary thyroid hydatid cyst.

PMID- 21713740
TI  - Excision of osteoid osteoma with intramedullary reaming: a new method.
AB  - Osteoid osteoma is a small benign bone tumor usually affects adolescents and
      young adults. Although this tumor mainly affects the shafts of long bones there
      have been several reports of subperiosteal and intramedullary involvement
      .Complete surgical excision is the classic treatment of choice for patients with
      osteoid osteoma. Despite the small size of the tumor, the operative procedure for
      its removal can be extensive .The surgeon may have to excise a significant piece
      of bone to be sure the lesion is removed. There is a risk of fracture if a large
      amount of bone is removed and therefore internal fixation, bone grafting, or both
      may be required. In recent years several techniques of minimally invasive
      treatment of osteoid osteoma have been proposed. We introduce intramedullary
      reaming as a minimally invasive procedure for the treatment of intramedullary
      osteoid osteoma in long bones.

PMID- 21713741
TI  - Cholangitis and choledocholithiasis after repair of duodenal atresia: a case
      report.
AB  - Cholelithiasis is a rare but known complication of surgery for duodenal atresia.
      Occurrence of choledocholithiasis as sequelae of duodenoduodenostomy is still
      rarer. Biliary stasis resulting from compression of common bile duct due to
      periductal fibrosis may predispose to gallstone formation. We are reporting a
      case of choledocholithiasis in a 6 year old child as a late post-operative
      complication of duodenoduodenostomy (for duodenal atresia in the neonatal
      period). To the best of our knowledge this is the first case of its kind reported
      in English literature. Cholecystectomy followed by choledocholithotomy was done
      and the patient had an uneventful recovery. Upper abdominal pain in any patient
      with a history of surgery for duodenal atresia in the past warrants a thorough
      evaluation for any biliary tract anomaly, cholecystitis, cholangitis,
      cholelithiasis or choledocholithiasis.

PMID- 21713742
TI  - Comments on "systemic complications and their risk factors among Tehranian blood
      donor, 2005".

PMID- 21713743
TI  - Prevention of high fructose-induced metabolic syndrome in male wistar rats by
      aqueous extract of Tamarindus indica seed.
AB  - Tamarindus indica is used as a traditional treatment for diabetes. To elucidate
      whether Tamarindus indica seed aqueous extract (TSE) ameliorates metabolic
      syndrome in hyperinsulinemic rats, we evaluated serum insulin,
      dehydroepiandrosterone sulfate (DHEAS), triglyceride (TG), total cholesterol
      (TC), very low density lipoprotein (VLDL), low density lipoprotein (LDL), high
      density lipoprotein (HDL), and glucose levels in fructose-fed rats. Animals were
      divided into three groups; control (C) receiving tap water, fructose-fed (F) and
      TSE-treated fructose-fed rats (F-T) both receiving tap water supplemented with
      10% (w/v) fructose. Water was prepared every day for a period of 8 weeks for all
      three groups. F-T rats were fed with TSE via gavage feeding at the dose of 20
      mg/0.5 ml distilled water/100 g body weight per day. Fasting serum glucose levels
      of three groups were comparable. TSE treatment prevented the increase in fasting
      serum insulin, TG, TC, VLDL, and LDL in the F-T group (P<0.01) when comparing
      with the F group. Fructose feeding led to a decrease in fasting serum DHEAS, and
      HDL levels in the F group (P<0.01) compared with the control. TSE treatment
      prevented the decrease in fasting serum DHEAS, and HDL levels in the F-T group
      (P<0.01) while these results were not seen in control rats. It is indicated that
      the hyperinsulinemia in fructose-fed insulin resistant rats are associated with
      low levels of DHEAS, and HDL; and high levels of TC, VLDL, LDL, and TG. TSE
      supplementation probably ameliorates metabolic syndrome due to the improved
      insulin action.

PMID- 21713744
TI  - The comparison of the effects of acute swimming stress on plasma corticosterone
      and leptin concentration in male and female rats.
AB  - The aim of this study was to investigate the effect of acute swimming stress on
      plasma corticosterone and leptin levels in female and male rats. Thirty- seven
      adult male (n=20) and female (n=20) Sprague Dawley rats (200-250 g weight) were
      used. The leptin and corticosterone levels were measured following swimming
      stress (10 minutes) or no stress. Plasma leptin and corticosterone were measured
      by ELISA system. The plasma leptin and corticosterone levels were significantly
      increased in female and male rats by swimming stress. Plasma leptin level was not
      correlated significantly with plasma corticosterone in all groups. There were no
      sex differences in leptin level among stressed and non stressed rats. The results
      suggest that changes in plasma leptin level could not be associated with
      stimulation of corticosterone secretion from adrenal glands and leptin secretion
      is not sex dependent.

PMID- 21713745
TI  - Effect of prophylactic low dose of methylprednisolone on postoperative new atrial
      fibrillation and early complications in patients with severe LV dysfunction
      undergoing elective off-pump coronary artery bypass surgery.
AB  - Atrial fibrillation (AF) is the most common arrhythmia after cardiothoracic
      surgery. AF following coronary artery bypass graft (CABG) is associated with an
      increase in morbidity, mortality, hemodynamic instability, thromboembolic events,
      severity of heart failure and ICU and hospital stay. Corticosteroids have a
      variety of beneficial effects on recovery after elective surgery. This study was
      designed to test the hypothesis that low dose of Methylprednisolone (MP) can
      affect post-CABG AF and early complications in patients with severe left
      ventricle dysfunction who underwent elective off-pump coronary artery bypass. A
      total of 120 patients with LV dysfunction undergoing elective off- pump CABG
      randomly received either MP or placebo. Diabetic patients and those who were
      receiving corticosteroids were excluded. The MP group received 5mg/kg of MP
      intravenously after induction of anesthesia and the placebo group received an
      equal volume of normal saline. We evaluated Post-CABG variables including
      incidence, duration and frequency of AF recurrence and early morbidity such as
      bleeding, infection, vomiting, renal and respiratory dysfunctions, ICU or
      hospital stay and early mortality. The mean age of patients was 62.11 +/- 12.34
      years with the 2.4 male to female ratio. AF occurred in 23(19.2%) patients. No
      significant difference in the incidence of new AF was found between the placebo
      (21.7%) and MP group (16.7%) (P=0.47). MP did not affect postoperative bleeding,
      infection, vomiting, renal and respiratory dysfunction and mortality; however, MP
      significantly reduced ICU and hospital length of stay. MP did not affect the
      incidence, duration and frequency of AF recurrence in patients with severe LV
      dysfunction undergoing off-pump CABG. However, MP could reduce ICU and hospital
      stay significantly in these patients.

PMID- 21713746
TI  - Antimicrobial resistant pattern of Escherichia coli strains isolated from
      pediatric patients in Jordan.
AB  - The present study was conducted to investigate antimicrobial resistant pattern of
      Escherichia coli (E. coli) strains isolated from clinical specimens of Jordanian
      pediatric patients during the period from January to December 2008. A total of
      444 E. coli strains were isolated from clinical specimens and tested for their
      susceptibility to different antimicrobial drugs. Overall, high resistance rate
      was observed for ampicillin (84%), followed by amoxicillin-clavulanic acid
      (74.3%), cotrimoxazole (71%), nalidixic acid (47.3%), cephalothin (41%). Lower
      resistance rates were observed for amikacin (0%) followed by Cefotaxime (11%),
      Ceftriaxone (11.7%), ciprofloxacin (14.5%), Norfloxacin (16.5%), gentamicin
      (17.3%) cephalexin (20.9%), Ceftazidime (22.5%), cefixime (29.6%), and cefaclor
      (32.8%). Ampicillin, amoxicillin-clavulanic acid and cotrimoxazole were found to
      be ineffective at in vitro inhibition of the E. coli of pediatric origin.
      Amikacin was highly effective for E. coli with susceptibility rate of 100%. The
      majority of E. coli strains were susceptible to third generation cephalosporins
      and fluoroquinolones.

PMID- 21713747
TI  - Learning outcomes in two different teaching approach in nursing education in
      Iran: e-learning versus lecture.
AB  - Traditional teaching methods used in medical education couldn't meet the need for
      keeping pace with up to date information. Present study has conducted in order to
      compare the effect of lecture and e-learning methods on nursing students'
      learning outcomes in the context of Iran. A cross-over design was applied. Study
      sample was consisted of 32 students which were in third semester of nursing
      bachelor program and were passing Maternal Child nursing course. The first part
      of the course was taught using lecture method during first four weeks; an e
      learning method was the technique used to educate the remained part of the course
      during the second four weeks. Students' learning outcomes in each method, opinion
      toward and participation with both educational methods was assessed. No
      significant difference was found between students exam scores in both methods.
      Considering students' opinion toward educational methods, no significant
      difference was found between two methods in general but students reported better
      "capability" and "independency" in e-learning method while lecture was obtained
      higher scores in "effectiveness on learning" and "motivation" characteristics. E
      learning can be used in teaching some nursing courses. It is recommended to use e
      learning method with appropriate interactive strategies and attractive virtual
      environments to motivate students.

PMID- 21713748
TI  - Influence of physiological factors on thyroid size determined by ultrasound.
AB  - According to its superficial anatomical location, the thyroid gland is easily
      accessible by sonography. Sonography allows an exact documentation of the size
      and thyroid volume. The relationship between thyroid volume and anthropometric
      characteristics is a matter of controversy. The aim of this study was to
      investigate thyroid volume and its determinants in healthy adult. A cross
      sectional study was performed from June2003 until April 2005 in 314 healthy
      adults aged over 18 years old in Yazd, Iran. Data were collected on age, sex, and
      weight and thyroid size by sonography. Mean of thyroid volume in male and female
      was 9.08 +/- 2.49 and 7.93 +/- 3.2 milliliter which the differences was
      significant (P<0.003).Differences between thyroid volume and weight was
      significant (P=0.001). Mean of female weight and proportion of thyroid volume to
      their weight was 61.83 +/- 12.09kg and 0.130 +/- 0.33. Mean of male weight and
      proportion of thyroid volume to their weight was 71.41 +/- 9.05kg and 0.126 +/-
      0.028 (P<0.003). Results of study is similar to other studies .Mean of thyroid
      volume in Yazd citizens is not differ from other Iranian but is different from
      other countries. This difference could be related to food intake habit,
      geographical region and daily oral iodine consumption.

PMID- 21713749
TI  - Correlation of tonsillectomy with palatine tonsil size.
AB  - We aimed to investigate the correlation of tonsillectomy with palatine tonsil
      size and to compare the differences of tonsil size and the need for surgery in
      children and adults. Also we can predict the outcome of tonsillectomy. We
      measured tonsil sizes in (height and width) in 150 children and 35 adults with
      hypertrophy of palatine tonsils and we measured the mass of tonsils and then the
      data analysis. In both groups of children and adults, tonsil sizes were
      significantly correlated with the rate of tonsillectomy. Tonsil size of grade 3
      and 4 were with a high tonsillectomy rate in adults but tonsil size grade 2, 3
      and 4 had a high tonsillectomy rate in children. Tonsillectomy correlated with
      tonsil size in both groups children and adults. The rate of tonsillectomy
      increased proportionally with tonsil sizes in both groups children and adults.

PMID- 21713750
TI  - Perioperative predictors and clinical outcome in early and late ICU discharge
      after off-pump coronary artery bypass surgery.
AB  - The duration of ICU (intensive care unit) stay in cardiac surgery patients has an
      important role in the rate of complications and costs. The aim of this study was
      to determine the role of perioperative risk factors in clinical outcome based on
      the time of ICU discharge. In this descriptive study, 219 patients undergoing off
      pump coronary artery bypass (OPCAB) surgery in Afshar Hospital in Yazd, an
      Iranian city, were divided into early (<=24 hrs) and late (>24 hrs) ICU discharge
      groups according to the duration of ICU stay. The preoperative, intraoperative
      and postoperative risk factors, the complications and the outcome were evaluated.
      Age, sex, hyperlipidemia, diabetes mellitus, previous myocardial infarction,
      renal failure, cerebrovascular accident, and level of hematocrit and creatinine
      were not significantly different between the two groups. Patients with
      hemodynamic instability, respiratory dysfunction, ejection fraction <35%,
      hypertension, inotrope administration, left main coronary artery involvement, use
      of intraaortic balloon pump (IABP) and arrhythmia had significantly higher
      mortality and longer ICU stay (>24 hrs) compared to others (P value <0.05). The
      duration of intubation was significantly lower in the early discharge group (7.8
      +/- 3.8 hrs compared to 17 +/- 9.9 hrs) than in the late discharge group. Time of
      ICU discharge depends on perioperative risk factors, and risk factor modification
      may improve clinical outcome.

PMID- 21713751
TI  - Burn scar reconstruction of the neck with FTSG obtained from lower abdominal
      skin.
AB  - Burns account for a significant proportion of injuries, and of these the face,
      neck, and anterior torso are commonly affected. Burn scars remain a lasting
      reminder of the insult both for the patient and the outside world. There is
      little doubt that the change in appearance and the limitation imposed by a burn
      scar contribute to negative body image. Treatment of hypertrophic scars in the
      neck has been quite challenging if there is no intact tissue for local flaps. So
      application of full-thickness skin grafts could be of great value. We applied
      full-thickness grafts obtained from lower abdominal skin for treatment of severe
      neck contractures in four patients when other treatment modalities such as local
      flaps could not be used. Full-thickness skin graft of the neck is a safe and
      reliable treatment option with fairly good functional and aesthetic results. It
      has little donor site morbidity in spite of providing a large surface area of
      full-thickness skin.

PMID- 21713752
TI  - Relationship between Helicobacter pylori infection and serum ferritin level in
      primary school children in Tehran-Iran.
AB  - Iron deficiency can cause cognitive and functional learning disorders in
      children. Some studies have reported a relationship between low serum ferritin
      levels in patients with anemia and Helicobacter pylori (H. pylori) infection.
      Therefore, we aimed to determine the relationship between these two common
      diseases. This descriptive analytical cross-sectional study was performed to
      assess serum ferritin levels and H. pylori antibody titers (IgG) among 6-12 year
      old healthy primary school children in Tehran during the academic year 2005-2006.
      Specimen collection was done by cluster and randomization methods (multistage
      sampling). Personal information and laboratory results were compiled in
      questionnaires and data were analyzed by descriptive and analytical statistics
      via SPSS software. 165 primary school children (43% boys, 57% girls) with mean
      age 9.2 +/- 1.5 years were enrolled in the study. H. pylori IgG antibody titer
      was positive in 26% of cases with mean values of 0.79 +/- 0.42 units in boys and
      0.75 +/- 0.39 units in girls, which showed a significant statistical difference
      (P=0.004). H. pylori infection was more common among children of large families
      or those with low economic status (P=0.002). 29% of children had low serum
      ferritin levels. Out of the children with low serum ferritin levels, 71% and 28%
      had negative and positive anti H. pylori antibody titers (IgG levels),
      respectively. Also, 296 children (25%) with normal ferritin levels had H. pylori
      infection. We did not find a significant relationship between H. pylori infection
      and low serum ferritin levels or iron deficiency anemia.

PMID- 21713753
TI  - Peri-implant soft tissue management through use of cultured gingival graft: a
      case report.
AB  - Tissue-engineered gingival graft was used for regenerating facial gingiva around
      an implant at lower left first premolar area with insufficient attached gingiva.
      Engineered gingival graft was produced by mixing 250 ml bovine skin collagen with
      250 ml nutritional medium containing human gingival fibroblasts (2*10(5)). 3
      months post-surgery, there were gains in the attached gingiva compared to pre
      surgery. The histological examination revealed a keratinized tissue on the
      treated site. Based on the result of this investigation, this graft was safe and
      capable of generating keratinized gingiva.

PMID- 21713754
TI  - Pleural and pericardial effusions: rare presentations of brucellosis, Iran.
AB  - We report a rare case of brucellosis presenting with pleural and pericardial
      effusions in a 35 year-old male rancher in Iran with fever and dyspnea. Such
      findings should prompt inclusion of brucellosis in the differential diagnosis in
      endemic areas.

PMID- 21713755
TI  - Trans-catheter therapy of Lutembacher syndrome: a case report.
AB  - Lutembacher syndrome refers to the rare combination of a congenital atrial septal
      defect and acquired mitral stenosis. Traditionally, Lutembacher syndrome has been
      corrected by surgical treatment. We describe two patients treated percutaneouly
      with a combined Inoue balloon valvuloplasty and septal defect closure using the
      Amplatzer septal occlusion device.

PMID- 21713756
TI  - Routine colonoscopy following acute uncomplicated diverticulitis.
AB  - BACKGROUND: The evidence supporting current recommendations that the colon should
      be evaluated following an initial episode of acute diverticulitis is poor. The
      aim of this study was to clarify whether acute uncomplicated diverticulitis is a
      valid indication for subsequent colonoscopy/computed tomography (CT)
      colonography. METHODS: This was a retrospective longitudinal study of patients
      with an initial presentation of acute uncomplicated diverticulitis on the basis
      of CT criteria, at a single institution between January 2004 and December 2008.
      RESULTS: A radiological diagnosis of acute uncomplicated diverticulitis was made
      in 292 patients. Some 205 patients underwent subsequent colonic evaluation or had
      undergone colonoscopy/CT colonography within the preceding 2 years. Colorectal
      polyps were present in 50 patients (24.4 per cent). Twenty patients (9.8 per
      cent) had hyperplastic polyps and 19 (9.3 per cent) had adenomas. Eleven patients
      (5.4 per cent) had advanced colonic neoplasia, including one (0.5 per cent) with
      a colorectal cancer. One patient had inflammatory bowel disease (IBD). The
      patients with colorectal cancer and IBD had clinical indicators that
      independently warranted colonoscopy. None of the 87 patients who did not undergo
      colonic evaluation had a diagnosis of colorectal cancer registered with the New
      Zealand Cancer Registry. CONCLUSION: The yield of advanced colonic neoplasia in
      this cohort was equivalent to, or less than that detected on screening
      asymptomatic average-risk individuals. In the absence of other indications,
      subsequent evaluation of the colon may not be required to confirm the diagnosis
      of diverticulitis.

PMID- 21713757
TI  - Polycomb group protein EZH2 is frequently expressed in inflammatory breast cancer
      and is predictive of worse clinical outcome.
AB  - BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a member of polycomb group
      proteins, is involved in the regulation of cell cycle progression and has been
      implicated in various human malignancies, including breast cancer, and also has
      been associated with aggressive tumor behavior. However, the clinical
      significance of EZH2 expression in inflammatory breast cancer (IBC), a rare but
      aggressive type of breast carcinoma, has not been explored. In this retrospective
      study, the authors examined EZH2 expression in IBC tumors and evaluated the
      relation between EZH2 expression and patient survival. METHODS: Tissue
      microarrays of 88 surgically resected IBC tumors were stained
      immunohistochemically for EZH2, and the authors evaluated the association of EZH2
      expression status with clinicopathologic factors and clinical outcome. RESULTS:
      The median follow-up for the entire cohort was 45.7 months, and the 5-year
      overall survival (OS) rate was 45%. EZH2 was expressed frequently in IBC tumors
      (75.7%) and was associated significantly with unfavorable prognostic factors,
      such as higher tumor grade, negative estrogen receptor status, and triple
      negative status (ie, negative for the estrogen, progesterone, and human epidermal
      growth factor 2 receptors). Univariate survival analysis indicated that patients
      who had EZH2-positive IBC had a significantly lower 5-year OS rate than patients
      who had EZH2-negative IBC (P = .01). In multivariate analysis, only positive EZH2
      status remained an independent predictor of worse OS. CONCLUSIONS: EZH2 was
      expressed frequently in IBC tumors. The current results indicated that EZH2
      expression status may be used to identify a subset of patients with IBC who have
      a relatively worse prognosis. Targeting EZH2 also may provide a novel strategy
      for improving the clinical outcome of patients with IBC.

PMID- 21713758
TI  - Long-term functional results and quality of life after transanal endoscopic
      microsurgery.
AB  - BACKGROUND: Of the few studies that have investigated quality-of-life (QoL)
      outcomes after transanal endoscopic microsurgery (TEM), the majority have
      reported only short-term follow-up data. This study assessed long-term clinical
      and instrumental outcomes (QoL, sexual, urinary and sphincter function) after TEM
      for extraperitoneal rectal cancer. METHODS: Preoperative and postoperative
      anorectal function was assessed in consecutive patients with benign rectal
      lesions or early rectal cancer, based on clinical scores and anorectal manometry.
      RESULTS: Between January 2000 and July 2005, 93 patients undergoing TEM completed
      the 60-month study protocol. The mean Wexner continence score increased from
      baseline at 3 months, began to decline within 12 months, and had returned to the
      preoperative value at 60 months. Urgency was reported by 65.0, 30.0 and 5 per
      cent of patients at 3, 12 and 60 months respectively (P < 0.050). A significant
      improvement was noted in various clinical and QoL scores at 12 and 60 months.
      Postoperative manometry values at 3 months were significantly lower than at
      baseline (P < 0.050), but had returned to preoperative values at 12 months.
      Tumour size of 4 cm or above was the only factor that significantly (P = 0.008)
      affected the rectal sensitivity threshold, the urge to defaecate threshold and
      the maximum tolerated volume at 3 months after TEM. CONCLUSION: TEM had no long
      term effect on anorectal function or QoL. Lower anal resting pressure at early
      follow-up was not associated with defaecation problems in patients who were
      continent before surgery.

PMID- 21713759
TI  - Human immunodeficiency virus-associated lung cancer in the era of highly active
      antiretroviral therapy.
AB  - BACKGROUND: Lung cancer is the leading cause of death among non-acquired
      immunodeficiency syndrome (AIDS)-defining malignancies. Because highly active
      antiretroviral therapy (HAART) has improved the survival of patients with human
      immunodeficiency virus (HIV), the authors evaluated lung cancer outcomes in the
      HAART era. METHODS: HIV-positive patients who were diagnosed with lung cancer at
      the authors' institution during the HAART era (1995-2008) were analyzed. Patient
      charts were reviewed for clinical and laboratory data. The CD4 count at diagnosis
      was treated as a continuous variable and subcategorized into distinct variables
      with 3 cutoff points (50 cells/mL, 200 cells/mL, and 500 cells/mL). Pearson
      correlation coefficients were estimated for each covariate studied. Survival was
      determined by using the Kaplan-Meier method. RESULTS: Of 80 patients, 73 had
      nonsmall cell lung cancer. Baseline characteristics were as follows: median
      patient age, 52 years; male, 80%; African Americans, 84%; injection drug users,
      25%; smokers, 100%; and previous exposure to antiretroviral agents, 55%. At the
      time of cancer diagnosis, the mean CD4 count was 304 cells/mL, and the mean viral
      load was 82,420 copies/mL. The latency between HIV diagnosis and lung cancer
      diagnosis was significantly shorter among women (4.1 years vs 7.7 years; P =
      .02), and 71% of patients received anticancer therapy. The 1-year and 3-year
      survival rates for stage IIIB/IV were 25% and 0%, respectively. Grade 3/4
      toxicities occurred in 60% of patients who received chemoradiation versus 36% of
      patients who received chemotherapy. Cancer-related survival was better for
      patients with CD4 counts >200 cells/mL (P = .0298) and >500 cells/mL (P = .0076).
      CONCLUSIONS: The latency from diagnosis of HIV to lung cancer was significantly
      shorter for women. Although outcomes for patients with lung cancer who have HIV
      remain poor, a high CD4 count was associated with improved lung cancer-related
      survival.

PMID- 21713760
TI  - An integrated analysis of germline and somatic, genetic and epigenetic
      alterations at 9p21.3 in glioblastoma.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most prevalent and deadly brain
      tumor. A variety of germline and somatic, genetic and epigenetic alterations at
      9p21.3, which encode CDKN2A/CDKN2B tumor suppressor genes, have been isolatedly
      reported to be associated with GBM risk and prognosis. METHODS: To obtain a
      comprehensive view of these events, we leveraged the wide-spectrum GBM data
      available from The Cancer Genome Atlas project and performed an integrated
      analysis by systematically evaluating 9p21.3-related germline single-nucleotide
      polymorphisms, somatic copy number alterations (CNAs), DNA methylation, and
      microRNAs (miRNAs) with regard to CDKN2A/CDKN2B expression and patient prognosis
      in GBM. RESULTS: Our multivariate analysis indicated that expression of CDKN2A
      and CDKN2B was both strongly affected by CNAs (P = 1.00 * 10(-4) and 2.37 * 10(
      14)). The miRNAs hsa-mir-126, hsa-mir-517a, and hsa-mir-125b exhibited
      significant negative correlations with CDKN2A expression (P = 0.003, 0.041, and
      0.050). Survival analysis showed that complete 9p21.3 loss and low CDKN2B
      expression were associated with worse prognosis for both tumor
      progression/recurrence-free survival (P = .041 and .019) and patient overall
      survival (P = .043 and .021) after adjustment for age and treatment, and that
      higher methylation at cg17449661 predicted poorer overall survival (P = .048).
      CONCLUSION: Representing one of the first attempts to systematically integrate
      various levels of alterations associated with the often complex cancer genomes
      and phenotypes, our study provided a holistic view and a mechanistic explanation
      over the functional connections of multiple 9p21.3-related events in GBM, as well
      as clinically useful biomarker information for predicting disease outcomes.

PMID- 21713761
TI  - FBI-1 promotes cell proliferation and enhances resistance to chemotherapy of
      hepatocellular carcinoma in vitro and in vivo.
AB  - BACKGROUND: The so-called factor that binds to inducer of short transcripts-1
      (FBI-1) purportedly plays an important role in tumorigenesis; however, its role
      in hepatocellular carcinoma (HCC) remains unknown. The objective of this study
      was to investigate the expression level, clinical relevance, and biologic
      function of FBI-1 in HCC. METHODS: Real-time quantitative reverse transcriptase
      polymerase chain reaction analysis, Western blot analysis, and
      immunohistochemical staining were used to detect expression levels of FBI-1 and
      to analyze its relation to clinicopathologic parameters and to the prognosis of
      patients with HCC. In addition, the biologic functions of FBI-1 in regulating
      cell proliferation, migration, and reaction to chemotherapy were detected by
      using HepG2 cells and SMMC-7721 cells; subsequently, the molecular mechanism of
      FBI-1 also was investigated. Finally, a xenograft mouse model was used to
      validate the observations obtained from in vitro studies. RESULTS: Expression
      levels of FBI-1 messenger RNA and protein were elevated significantly in HCC
      tissues compared with adjacent nontumorous liver tissues (ANLTs). Increased FBI-1
      expression was correlated with multiple tumor nodes, Edmondson-Steiner grade, and
      a poor prognosis in patients with HCC (P < .05). In vitro studies revealed that
      FBI-1 was capable of promoting cell proliferation (but not cell migration) by
      regulating the cell cycle regulation proteins p53, p21, and p27. In addition, FBI
      1 could inhibit cell death induced by 5-fluorouracil or doxorubicin through
      suppressing the activation of p53. Consistent with the in vitro data, FBI-1 was
      capable of promoting cell proliferation and enhancing chemotherapy resistance of
      HCC in vivo. CONCLUSIONS: The current findings indicated that FBI-1 plays an
      important role in HCC carcinogenesis and chemotherapy tolerance, and FBI-1 may
      served as a novel prognostic marker and therapeutic target for HCC.

PMID- 21713762
TI  - Reirradiation and hyperthermia for radiation-associated sarcoma.
AB  - BACKGROUND: The objective of this study was to evaluate the role of reirradiation
      and hyperthermia in the treatment of radiation-associated sarcoma (RAS) in the
      thoracic region, which is an increasing, yet extremely rare condition with a poor
      prognosis. METHODS: Between 1979 and 2009, 16 patients with RAS in the thoracic
      region were treated in the Academic Medical Center and the Institute Verbeeten
      with reirradiation and hyperthermia. In 13 patients, this treatment was given for
      unresectable disease and 3 times after resection as adjuvant treatment. The
      median latency period between the original malignancy diagnosis and the RAS
      diagnosis was 86 months (range 19-212 months). Histology was angiosarcoma in 11
      patients (69%). The literature on reirradiation with or without hyperthermia for
      RAS was reviewed. RESULTS: The median survival was 15.5 months (range, 3-204
      months). Four patients were not evaluable for response. The response rate for the
      remaining 12 patients was 75% (7 complete responses and 2 partial responses). Six
      patients remained free of local failure until death (5 months and 7 months) or
      last follow-up (8 months, 11 months, 39 months, and 68 months). CONCLUSIONS: The
      current study indicates that combined reirradiation and hyperthermia for RAS in
      the thoracic region is feasible. The high response rate and the possibility of
      durable local control suggest that this treatment is promising.

PMID- 21713763
TI  - Serum cell-free DNA in renal cell carcinoma: a diagnostic and prognostic marker.
AB  - BACKGROUND: Currently, there are no established diagnostic and prognostic serum
      markers for renal cell carcinoma (RCC). The objective of this study was to
      evaluate the putative significance of serum cell-free DNA. METHODS: Preoperative
      serum samples from 200 consecutive patients with sporadic, solid renal tumors
      were analyzed (157 patients with RCC and 43 patients with benign renal tumors).
      Quantitative real-time polymerase chain reaction was used to assess total cell
      free DNA (ring finger protein 185 [RNF185]) and CpG island methylation of Ras
      association domain family member 1A (RASSF1A) von Hippel-Lindau (VHL),
      prostaglandin-endoperoxidase synthase 2 (PTGS2), and P16 (cyclin-dependent kinase
      inhibitor 2A). Associations with RCC, pathologic variables, and disease-specific
      survival were evaluated. RESULTS: Total cell-free DNA levels and CpG island
      methylation of RASSF1A and VHL were highly diagnostic for RCC with an area under
      the receiver operating characteristic curve of 0.755, 0.705, and 0.694,
      respectively. VHL methylation was detected more frequently in patients with clear
      cell RCC than in those with other subtypes (P = .007). Total cell-free DNA levels
      were higher in patients with metastatic RCC (P < .001) and necrotic RCC (P =
      .003) and were associated with poorer disease-specific survival (P < .001). In
      multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score
      (P < .001) and categorized total cell-free DNA levels (P = .028) were retained as
      independent prognostic factors. CONCLUSIONS: The current results indicated that
      cell-free DNA represents a novel serum-based diagnostic and prognostic biomarker
      for RCC. Total serum cell-free DNA levels and CpG island methylation of RASSF1A
      and VHL may be useful diagnostic biomarkers for RCC. VHL methylation of cell-free
      DNA is suggestive of clear cell RCC. Total serum cell-free DNA may be a useful
      prognostic biomarker that may assist in tailoring postoperative surveillance and
      therapy. External prospective validation of these data will be required.

PMID- 21713764
TI  - Comparison of tumor response by Response Evaluation Criteria in Solid Tumors
      (RECIST) and modified RECIST in patients treated with sorafenib for
      hepatocellular carcinoma.
AB  - BACKGROUND: A significant improvement in overall survival (OS) was demonstrated
      in patients with advanced hepatocellular carcinoma (HCC) who received sorafenib
      (Sor) in the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, in
      contrast to a response rate (RR) of 2% assessed according to Response Evaluation
      Criteria in Solid Tumors (RECIST). Modified RECIST (mRECIST) were developed to
      assess the response in patients with HCC, based on measurement of viable tumor
      with arterial enhancement on a computed tomography (CT) scan. In the current
      study, mRECIST were evaluated and were compared with RECIST in patients who
      received Sor for advanced HCC. METHODS: The authors retrospectively analyzed 53
      patients who received Sor for advanced HCC. Patients must to have undergone a 4
      phase CT scan before treatment and repeatedly thereafter. CT scans were analyzed
      using RECIST 1.1 and mRECIST. RESULTS: The rates of objective response (OR),
      stable disease (SD), and progressive disease (PD) were 2%, 79%, and 19%,
      respectively, according to RECIST and 23%, 57%, and 21%, respectively, according
      to mRECIST (P < .001). Patients who achieved an OR according to mRECIST had a
      longer OS than nonresponding patients with SD or PD (median OS, 18 months and 8
      months, respectively; P = .013). In the 42 patients who achieved SD according to
      RECIST, OS differed depending on tumor response according to mRECIST, with a
      median OS of 17 months, 10 months, and 4 months for patients who achieved an OR
      (n = 11), SD (n = 29), and PD (n = 2), respectively (P = .016). CONCLUSIONS: The
      current series validated mRECIST in patients who received Sor for advanced HCC.
      The majority of patients who had SD according to RECIST had a different prognosis
      according to mRECIST. The results indicated that, for patients with HCC, mRECIST
      should be used for the standard assessment of treatment efficacy, particularly in
      patients who are receiving antiangiogenic drugs.

PMID- 21713765
TI  - Identification of potential prognostic biomarkers in patients with untreated,
      advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B
      80303).
AB  - BACKGROUND: Patients with advanced stage adenocarcinoma of the pancreas have a
      poor prognosis. The identification of prognostic and/or predictive biomarkers may
      help stratify patients so that therapy can be individualized. METHODS: Serum
      samples from patients enrolled in the Cancer and Leukemia Group B 80303 phase 3
      trial, "Randomized Study of Gemcitabine With Versus Without Bevacizumab in
      Patients With Locally Advanced or Metastatic Adenocarcinoma of the Pancreas" were
      used to discover novel biomarkers. For the discovery phase, 40 sera were selected
      based on length of survival and type of therapy, and subjected to liquid
      chromatography coupled to tandem mass spectrometry analysis (LC-MS-MS). The top
      features (proteins) were then further selected for validation by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Quantification by nano-LC-MS-MS resulted in
      1452 peptides mapping to 156 proteins across all 40 samples, 92 of which had 2 or
      more peptides. After curation of the data, the authors selected 1 putative
      prognostic protein, alpha 1-antichymotrypsin (AACT), and 2 putative predictive
      proteins, histidine-rich glycoprotein (HRG) and complement factor H (CFH), for
      validation by ELISA. AACT was found to be negatively correlated with overall
      survival (tau = -0.30 [-0.38, -0.22]; P < .00001). There was no evidence for
      interaction with bevacizumab and HRG, but there was some evidence for a weak
      positive correlation of HRG with overall survival (tau = 0.11 [0.03, 0.19]; P <
      .01). CFH was found to be neither a predictive nor a prognostic factor for
      overall survival. CONCLUSIONS: AACT may be a useful prognostic marker in patients
      with advanced stage pancreatic carcinoma, although additional validation studies
      are needed.

PMID- 21713766
TI  - Preclinical xenograft models of human sarcoma show nonrandom loss of aberrations.
AB  - BACKGROUND: Human tumors transplanted into immunodeficient mice (xenografts) are
      good preclinical models, and it is important to identify possible systematic
      changes during establishment and passaging in mice. METHODS: High-resolution
      microarray-based comparative genomic hybridization (array CGH) was used to
      investigate how well a series of sarcoma xenografts, including 9
      patient/xenograft pairs and 8 early versus late xenograft passage pairs,
      represented the patient tumor from which they originated. RESULTS: In all
      analyses, the xenografts were more similar to their tumor of origin than other
      xenografts of the same type. Most changes in aberration patterns were toward a
      more normal genome complement, and the increased aberrations observed were mostly
      toward more loss. In general, the changes were scattered over the genome, but
      some changes were significant in osteosarcomas. These were rather focused and
      consistent with amplifications frequent in patient samples, involving the genes
      platelet-derived growth factor receptor A (PDGFRA), cysteine-rich hydrophobic
      domain 2 (CHIC2), FIP-like 1 (FIP1L1), ligand of numb-protein X1 (LNX1), RAS-like
      family 11 member B (RASL11B), and sec1 family domain containing 2 (SCFD2),
      probably a sign of continued tumor progression. Some changes that disappeared may
      have been involved in host-stroma interactions or chemotherapy resistance,
      possibly because of the absence of selection in the mouse. CONCLUSIONS: Direct
      xenografts reflected well the genomic patterns of their tumors of origin. The few
      significant aberrations that were lost during passaging in immune-defective mice
      may have been caused by the lack of selection in the new host, whereas
      aberrations that were gained appeared to be the result of general tumor
      progression rather than model-specific artifacts.

PMID- 21713767
TI  - A prospective phase 2 study of surgery followed by chemotherapy and radiation for
      superior sulcus tumors.
AB  - BACKGROUND: The optimal treatment for locally advanced superior sulcus tumors is
      not clear. The authors report long-term results of a trial examining the safety
      and efficacy of surgery followed by concurrent chemoradiation therapy for this
      disease. METHODS: Thirty-two patients with resectable or marginally resectable
      superior sulcus tumors at The University of Texas MD Anderson Cancer Center from
      1994 to 2010 were enrolled in a prospective trial. Surgery involved segmentectomy
      or lobectomy with en bloc resection of the involved chest wall and complete nodal
      staging; radiation therapy (RT) began 14 to 42 days later to a dose of 60 grays
      (Gy) in 50 1.2-Gy fractions if surgical margins were negative or 64.8 Gy in 54
      1.2-Gy fractions if margins were positive. Two cycles of etoposide (50 mg/m(2) )
      and cisplatin (50 mg/m(2) ) were given during RT, and another 3 cycles were given
      after RT. Eleven patients underwent prophylactic cranial irradiation (PCI).
      RESULTS: The protocol completion rate was 78%. Gross total resection was
      accomplished in all 32 patients; 28% underwent R1 resection. Operative mortality
      was 0%. The most common surgical complication was postoperative pneumonia (25%).
      At a median follow-up time of 53.4 months (range, 2-154 months), the 2-year, 5
      year, and 10-year rates of locoregional control were 84%, 76%, and 76%; distant
      metastasis-free survival, 52%, 48%, and 48%; disease-free survival, 49%, 45%, and
      45%; and overall survival, 72%, 50%, and 45%, respectively. The brain was the
      most common site of distant failure (n = 5), but no patient who received PCI
      experienced brain metastasis. CONCLUSIONS: Surgery followed by postoperative
      chemoradiation is safe and effective for the treatment of marginally resectable
      superior sulcus tumors.

PMID- 21713768
TI  - The prognostic impact of tumor cell expression of estrogen receptor-alpha,
      progesterone receptor, and androgen receptor in patients irradiated for nonsmall
      cell lung cancer.
AB  - BACKGROUND: The current study was performed to investigate the potential impact
      of tumor cell expression of estrogen receptor-alpha (ER-alpha), progesterone
      receptor (PR), and androgen receptor (AR) on the outcomes of patients who
      received radiotherapy (RT) for non-small cell lung cancer (NSCLC). METHODS: Tumor
      cell expression of ER-alpha, PR, and AR as well as 9 additional potential
      prognostic factors were retrospectively evaluated in 64 patients who underwent RT
      for AJCC stage II/III NSCLC. The endpoints investigated were locoregional
      control, metastases-free survival, and overall survival. The additional potential
      prognostic factors were age, gender, Karnofsky performance score, histology, T
      classification, N classification, surgery, smoking during RT, and hemoglobin
      levels during RT. Subgroup analyses were performed for women and men. RESULTS: On
      univariate analysis, locoregional control was not found to be associated with
      expression of PR or AR. ER-alpha expression demonstrated a strong trend toward
      worse locoregional control. On multivariate analysis, ER-alpha expression was
      found to be significantly associated with worse locoregional control (risk ratio
      [RR], 3.12; P = .035). On univariate analysis, metastases-free survival was not
      associated with expression of ER-alpha, PR, or AR. On univariate analysis,
      survival was found to be negatively associated with expression of ER-alpha (P =
      .003) but not with PR or AR expression. On multivariate analysis, ER-alpha
      expression maintained significance (RR, 2.73; P = .022). CONCLUSIONS: Tumor cell
      expression of ER-alpha was found to be a negative prognostic factor for treatment
      outcomes in both women and men. Expression of PR and AR was not associated with
      outcomes.

PMID- 21713769
TI  - Axillary lymph node failure in patients treated with accelerated partial breast
      irradiation.
AB  - BACKGROUND: Data on the risk of axillary failure (AF) after accelerated partial
      breast irradiation (APBI) are limited. In this study, the authors determined the
      rate of AF and regional lymph node failure (RNF) in patients who received various
      forms of APBI and identified factors that were associated with its occurrence.
      METHODS: In total, 534 patients with early stage breast cancer were treated at
      William Beaumont Hospital with APBI, including 466 patients (87%) with invasive
      breast cancer and 68 patients (13%) with ductal carcinoma in situ. Clinical
      variables (patient age, tumor location), pathologic variables (tumor size, grade,
      estrogen receptor status, margin status, lymph node status), and treatment
      related variables (receipt of hormone and systemic chemotherapy) were analyzed to
      determine which factors were associated with AF and RNF. The median length of
      follow-up was 63 months (range, 1-201 months). RESULTS: The 5-year actuarial AF
      rate was 0.19%. Three patients (0.56%) developed RNF (all patients initially had
      invasive breast cancer) with a 5-year actuarial rate of 0.37%. Two of the
      regional recurrences were in the supraclavicular fossa, and 1 was in the axilla.
      No variables were associated with AF. However, patient numbers were very small.
      The median survival after RNF was 0.8 years (range, 0.3-1.7 years), and 2 of the
      3 patients died of disease. CONCLUSIONS: The rate of AF and RNF after APBI was
      low and appeared to be similar to the rate observed with whole-breast
      irradiation. No variables were associated with a higher rate of AF after APBI.

PMID- 21713770
TI  - Molecular organization and timing of Wnt1 expression define cohorts of midbrain
      dopamine neuron progenitors in vivo.
AB  - Midbrain dopamine (MbDA) neurons are functionally heterogeneous and modulate
      complex functions through precisely organized anatomical groups. MbDA neurons are
      generated from Wnt1-expressing progenitors located in the ventral mesencephalon
      (vMes) during embryogenesis. However, it is unclear whether the progenitor pool
      is partitioned into distinct cohorts based on molecular identity and whether the
      timing of gene expression uniquely identifies subtypes of MbDA neurons. In this
      study we show that Wnt1-expressing MbDA progenitors from embryonic day (E)8.5
      12.5 have dynamic molecular identities that correlate with specific spatial
      locations in the vMes. We also tested the hypothesis that the timing of Wnt1
      expression in progenitors is related to the distribution of anatomically distinct
      cohorts of adult MbDA neurons using genetic inducible fate mapping (GIFM). We
      demonstrate that the Wnt1 lineage contributes to specific cohorts of MbDA neurons
      during a 7-day epoch and that the contribution to MbDA neurons predominates over
      other ventral Mb domains. In addition, we show that calbindin-, GIRK2-, and
      calretinin-expressing MbDA neuron subtypes are derived from Wnt1-expressing
      progenitors marked over a broad temporal window. Through GIFM and quantitative
      analysis we demonstrate that the Wnt1 lineage does not undergo progressive
      lineage restriction, which eliminates a restricted competence model of generating
      MbDA diversity. Interestingly, we uncover that two significant peaks of Wnt1
      lineage contribution to MbDA neurons occur at E9.5 and E11.5. Collectively, our
      findings delineate the temporal window of MbDA neuron generation and show that
      lineage and timing predicts the terminal distribution pattern of MbDA neurons.

PMID- 21713771
TI  - Timing of Sonic hedgehog and Gli1 expression segregates midbrain dopamine
      neurons.
AB  - The ventral midbrain (vMb) is organized into distinct anatomical domains and
      contains cohorts of functionally distinct subtypes of midbrain dopamine (mDA)
      neurons. We tested the hypothesis that genetic history and timing of gene
      expression within mDA neuron progenitors impart spatial diversity. Using genetic
      inducible fate mapping to mark the Sonic hedgehog (Shh) and Gli1 lineages at
      varying embryonic stages, we performed a quantitative and qualitative comparison
      of the two lineages' contribution to the mDA neuron domains. Dynamic changes in
      Shh and Gli1 expression in the vMb primordia delineated their spatial
      contribution to the embryonic day 12.5 vMb: Both lineages first contributed to
      the medial domain, but subsequently the Gli1 lineage exclusively contributed to
      the lateral vMb while the Shh lineage expanded more broadly across the vMb. The
      contribution of both lineages to the differentiated mDA neuron domain was
      initially biased anteriorly and became more uniform across the anterior/posterior
      vMb throughout development. Our findings demonstrate that the early Shh and Gli1
      lineages specify mDA neurons of the substantia nigra pars compacta while the late
      Shh and Gli1 lineages maintain their progenitor state longer in the posterior vMb
      to extend the production of mDA neurons in the ventral tegmental area. Together,
      our study demonstrates that the timing of gene expression along with the genetic
      lineage (Shh or Gli1) within the neural progenitors segregate mDA neurons into
      distinct spatial domains.

PMID- 21713772
TI  - Basal level insulin delivery: in vitro release, stability, biocompatibility, and
      in vivo absorption from thermosensitive triblock copolymers.
AB  - The major goal of this study was to develop the biodegradable and biocompatible
      thermosensitive polylactic acid-polyethylene glycol-polylactic acid triblock
      copolymer-based delivery systems for controlled release of basal level insulin
      for a longer duration after single subcutaneous injection. Insulin was dispersed
      into aqueous copolymer solutions to prepare the delivery system. The in vitro
      release profile of insulin from delivery systems was studied at 37 degrees C in
      phosphate-buffered saline. Stability of released insulin was investigated using
      circular dichroism, differential scanning calorimetry, and matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry. A 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide assay and skin histology were used to
      determine the in vitro and in vivo biocompatibility of the delivery systems,
      respectively. Streptozotocin-induced diabetic rat model was used to study the in
      vivo absorption and bioactivity of insulin. In vitro release studies indicated
      that the delivery systems released insulin over 3 months in structurally stable
      form. The delivery systems were biocompatible in vitro and in vivo. In vivo
      absorption and bioactivity studies demonstrated elevated insulin level and
      corresponding decreased blood glucose level in diabetic rats. Thus, the delivery
      systems released insulin at a controlled rate in vitro in conformationally and
      chemically stable form and in vivo in biologically active form up to 3 months.

PMID- 21713773
TI  - Qualification of FTIR spectroscopic method for protein secondary structural
      analysis.
AB  - Fourier transform infrared (FTIR) spectroscopy is widely used to study protein
      secondary structure both in solution and in the solid state. The FTIR
      spectroscopic method has also been employed as a characterization method by the
      biopharmaceutical industry to determine the higher order structure of protein
      therapeutics, and to determine if any changes in protein conformation have
      occurred as a result of changes to process, formulation, manufacture, and storage
      conditions. The results of these studies are often included in regulatory
      filings; when comparability is assessed, the comparison is often qualitative. To
      demonstrate that the method can be quantitative, and is suitable for these
      intended purposes, the precision and sensitivity of the FTIR method were
      evaluated. The results show that FTIR spectroscopic analysis is reproducible with
      suitable method precision, that is, spectral similarity of replicate measurements
      is greater than 90%. The method can detect secondary structural changes caused by
      pH and denaturant. The sensitivity of the method in detecting structural changes
      depends on the extent of the changes and their impact on the resulting spectral
      similarity and characteristic FTIR bands. The results of these assessments are
      described in this paper.

PMID- 21713774
TI  - Functionalized lipid nanoparticles-cellophane hybrid films for molecular
      delivery: preparation, physicochemical characterization, and stability.
AB  - Lipid nanoparticles functionalized with the sunscreen 2,4-dihydroxybenzophenone
      (FLNPs) have been prepared by the ultrasound method and embedded in highly
      hydrophilic cellophane supports (regenerated cellulose, RC), creating
      biocompatible hybrid films (RC-FLNPs samples). The morphology of the FLNPs was
      studied with transmission microscopy, whereas the surface and interior chemical
      composition was analyzed by micro-Raman spectroscopy. RC-FLNPs hybrid films were
      prepared from the immersion of two cellophane supports with different thicknesses
      and water uptake properties (RC-3 and RC-6) in an aqueous dispersion of FLNPs.
      The structure of this hybrid material was visualized with bright-field
      microscopy, which clearly showed the inclusion of the FLNPs in the cellophane
      matrix. The stability of the RC-FLNPs films with respect to both aqueous
      environments and time was demonstrated by NaCl diffusion measurements. The
      reduction in the diffusion coefficient through the nanoparticle-modified films
      compared with the original supports confirms the presence of nanoparticles for
      concentration gradients of up to 0.4 M (osmotic pressure around 10 bar),
      indicating the stability of the hybrid hydrophilic material, even in aqueous
      environments and under matter flow conditions for a period of 21 days.

PMID- 21713775
TI  - Prognostic significance of postoperative complications after hepatectomy for
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatectomy is one of the best curative therapies for hepatocellular
      carcinoma (HCC). The negative impact of postoperative complications on long-term
      survival has been investigated in patients with several kinds of cancers. To
      clarify the impact of postoperative complications on long-term survival in
      patients who undergo hepatectomy for HCC, we conducted a comparative analysis of
      376 patients using the modified Clavien classification and identified the
      predictors of postoperative complications. METHODS: Patients were assigned into
      two groups: those with (N = 177) and those without complications (N = 199). The
      clinical data, surgical outcome, and long-term survival of patients were analyzed
      retrospectively. RESULTS: The cumulative overall survival rates of the patients
      with complications were significantly less than those of the patients without
      complications (P < 0.01). Multivariate logistic regression analysis revealed that
      intraoperative blood transfusion (P = 0.04), longer operation time (P = 0.02),
      use of Pringle's maneuver (P < 0.01), and use of the thoraco-abdominal approach
      (P = 0.01) were independent risk factors for postoperative complications.
      CONCLUSIONS: Postoperative complications (major or minor) are one of prognostic
      indicators in hepatectomy for HCC. The present study suggests that high quality
      surgical technique to minimize complications will improve the prognosis of HCC.

PMID- 21713776
TI  - A modified technique for end-to-side pancreaticojejunostomy by purse-string
      suture.
AB  - BACKGROUND: Pancreatic fistula is a leading cause of morbidity and mortality
      after pancreaticoduodenectomy. We designed a modified technique, by which the
      pancreatic stump was invaginated into the jejunal loop by purse-string suture.
      METHODS: From June 2008, 18 cases of patients were performed with this modified
      technique, and the morbidity and mortality were calculated. RESULTS: All cases
      recovered well from pancreaticoduodenectomy, and none of them occurred pancreatic
      fistula. The complications included: hemorrhage, wound infection, pulmonary
      infection, and ascite. CONCLUSIONS: Invagination anatomosis by purse-string
      suture could be performed safely and reduced the leakage rate of
      pancreaticojejunostomy.

PMID- 21713777
TI  - More than one pulmonary resections or combined lung-liver resection in 79
      patients with metastatic colorectal carcinoma.
AB  - BACKGROUND: The way to select patients who will benefit from surgical resection
      of pulmonary metastases of colorectal carcinoma (CRC) remains unclear. METHODS:
      We analyze overall survival and potential prognostic factors in 101 pulmonary
      resections of CRC metastases in 79 patients, focusing on cases with repeated
      pulmonary resection or with hepatic metastasectomy. RESULTS: Number of
      pathological pulmonary metastases was higher than that of preoperatively
      suspected pulmonary nodules in 18% of the resections. Morbidity rate was 16.5%.
      There was no mortality. Five-year survival rates from the resection of the CRC
      and from the first pulmonary metastasectomy were 74.6% and 53.3%, respectively.
      Prognosis did not decrease in patients with history of hepatic metastasectomy or
      in those in which repeated pulmonary resection was performed. Age >=70,
      preoperative carcinoembrionary antigen (CEA) >=5 ng/dl and mediastinal lymph node
      involvement entailed worse prognosis. Pathological lymph node involvement and age
      were shown as independent prognostic factors in the multivariate analysis.
      CONCLUSIONS: Resection of pulmonary metastases of CRC is a safe procedure, with 5
      year survival rates over 50%. History of resected hepatic metastases or needs for
      more than one pulmonary resection do not seem to decrease survival rates. Only
      lymph node involvement and age seem to be clearly associated to worse prognosis.

PMID- 21713778
TI  - Adjuvant imatinib treatment after R0 resection for patients with high-risk
      gastrointestinal stromal tumors: a median follow-up of 44 months.
AB  - BACKGROUND: The optimal duration of Imatinib adjuvant treatment for patients with
      high-risk gastrointestinal stromal tumors (GISTs) is uncertain. PATIENTS AND
      METHODS: A total of 90 patients with high-risk GISTs after curative resection
      were recruited into this non-randomized case-control study, including 35 having
      Imatinib adjuvant therapy and 55 having follow-up alone. The recurrence-free
      survival (RFS) was compared. RESULTS: After a median follow-up of 44.0 months, a
      significantly reduced recurrence rate was observed in the treatment group than
      the control group (17.1% vs. 78.2%, P = 0.000). One-year, 2-year, and 3-year RFS
      rates were 100% vs. 70.9%, 88.0% vs. 37.8%, and 88.0% vs. 27.5%, respectively;
      with a significant advantage for Imatinib adjuvant therapy versus the surgery
      only (P = 0.000, HR 0.122, 95% CI 0.041-0.363). Continuation Imatinib treatment
      further improved RFS by comparison with the interruption treatment (both 2-year
      and 3-year RFS were 95.8% vs. 63.6%, P = 0.011, HR 0.103, 95% CI 0.012-0.883).
      There were no serious adverse events in the adjuvant therapy group. CONCLUSIONS:
      Imatinib Adjuvant therapy could significantly prolong the RFS of patients with
      high-risk GISTs. Extended Imatinib adjuvant treatment strategy may further reduce
      the risk of relapse with a low drug resistance rate and toxicity profile.

PMID- 21713779
TI  - Role of the lymph node ratio in pancreatic ductal adenocarcinoma. Impact on
      patient stratification and prognosis.
AB  - BACKGROUND: Survival after resection of pancreatic adenocarcinoma is poor.
      Several prognostic factors such as the status of the resection margin, lymph node
      status, or tumor grading have been identified. Aim of the study was to evaluate
      the prognostic significance of the lymph node ratio (LNR) for resected pancreatic
      ductal adenocarcinoma. MATERIALS AND METHODS: Data were collected from 101
      patients who had undergone pancreatoduodenectomy for pancreatic ductal
      adenocarcinoma. Patients were divided into four groups according to the absolute
      LNR (0, 0-0.199, 0.2-0.399, >0.4). Kaplan-Meier and Cox proportional hazard
      models were used to evaluate the prognostic effect. RESULTS: The actuarial 3- and
      5-year survival rates were 32 and 17%, respectively. The median survival was 19
      months. Patients with LNR 0/0-0.199/0.2-0.399/>0.4 survived 40.2/30.5/18.1, and
      13.6 months, respectively (P = 0.001). At the multivariate analysis, lymph node
      status was not found to be a significant prognostic factor; on the contrary LNR
      >0.2 (P = 0.007), positive resection margin (P = 0.001), and grading (P = 0.05)
      were significantly related to survival. CONCLUSION: LNR is a more powerful
      predictor of survival than the lymph node status in patients undergoing
      pancreaticoduodenectomy for ductal adenocarcinoma.

PMID- 21713780
TI  - Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive
      surgery and HIPEC: a systematic review of survival, mortality, and morbidity.
AB  - Gastric cancer with peritoneal carcinomatosis has an extremely poor prognosis,
      which may be improved with cytoreductive surgery (CRS) combined with heated
      intraperitoneal chemotherapy (HIPEC). We systematically reviewed the literature
      regarding the efficacy of CRS + HIPEC in these patients. Electronic databases
      were searched from 2000 to 2010. Following CRS + HIPEC, overall median survival
      was 7.9 months and improved to 15 months for patients with completeness of
      cytoreduction scores of 0/1, however with a 30-day mortality rate of 4.8%.

PMID- 21713963
TI  - Near-field dosimetry for in vitro exposure of human cells at 60 GHz.
AB  - Due to the expected mass deployment of millimeter-wave wireless technologies,
      thresholds of potential millimeter-wave-induced biological and health effects
      should be carefully assessed. The main purpose of this study is to propose,
      optimize, and characterize a near-field exposure configuration allowing
      illumination of cells in vitro at 60 GHz with power densities up to several tens
      of mW/cm(2) . Positioning of a tissue culture plate containing cells has been
      optimized in the near-field of a standard horn antenna operating at 60 GHz. The
      optimal position corresponds to the maximal mean-to-peak specific absorption rate
      (SAR) ratio over the cell monolayer, allowing the achievement of power densities
      up to 50 mW/cm(2) at least. Three complementary parameters have been determined
      and analyzed for the exposed cells, namely the power density, SAR, and
      temperature dynamics. The incident power density and SAR have been computed using
      the finite-difference time-domain (FDTD) method. The temperature dynamics at
      different locations inside the culture medium are measured and analyzed for
      various power densities. Local SAR, determined based on the initial rate of
      temperature rise, is in a good agreement with the computed SAR (maximal
      difference of 5%). For the optimized exposure setup configuration, 73% of cells
      are located within the +/-3 dB region with respect to the average SAR. It is
      shown that under the considered exposure conditions, the maximal power density,
      local SAR, and temperature increments equal 57 mW/cm(2) , 1.4 kW/kg, and 6 
      degrees C, respectively, for the radiated power of 425 mW.

PMID- 21713964
TI  - alpha-Methylacyl-CoA racemase expression and lethal prostate cancer in the
      Physicians' Health Study and Health Professionals Follow-up Study.
AB  - BACKGROUND: alpha-Methylacyl-CoA racemase (AMACR) is an enzyme that serves as a
      diagnostic biomarker of prostate cancer in clinical practice. Recent studies
      suggest that low AMACR expression is associated with biochemical recurrence and
      the development of fatal disease. METHODS: We conducted a prospective cohort
      study among 920 men aged 47-84 years, who were diagnosed with prostate cancer in
      the Physicians' Health Study and the Health Professionals Follow-up Study
      cohorts, and whose resected tissue specimens were available for
      immunohistochemical analysis. We used Cox proportional hazards regression to
      evaluate the association of AMACR expression with lethal prostate cancer over a
      20-year follow-up period. RESULTS: In total, 68 men died from prostate cancer,
      and an additional 18 developed bony metastases during follow-up. We found that
      lower AMACR intensity was associated with higher prostate-specific antigen levels
      (P = 0.003) and more advanced clinical stage (P = 0.06) at diagnosis, and a
      nonsignificant trend for higher risk of lethal outcomes. The hazard ratio (HR)
      comparing the lowest to the highest quartile of AMACR expression intensity was
      1.53 ((95% CI: 0.86-2.73), P-for-trend across quartiles = 0.07); this trend was
      further attenuated after adjustment for age, Gleason score, stage, and cohort
      with a HR of 1.24 (95% CI: 0.69-2.22), P-for-trend = 0.23. CONCLUSIONS: Low AMACR
      expression in primary tumor specimens was not independently associated with the
      development of metastatic and lethal prostate cancer after treatment over a 20
      year follow-up period, after adjustment for important clinical covariates at
      diagnosis.

PMID- 21713965
TI  - Serum prostate specific antigen changes in cynomolgus monkeys (Macaca
      fascicularis) on a high sugar high fat diet.
AB  - BACKGROUND: An inverse relationship between serum prostate specific antigen (PSA)
      levels and body mass index (BMI) has been reported in men but not in any animal
      model. METHODS: Serum PSA in a colony of cynomolgus monkeys was assayed and
      correlated to body weight, prostate weight, and age. In addition, 15 animals were
      selected and fed a high sugar high fat (HSHF) diet for 49 weeks to increase their
      BMI and correlate it to PSA RESULTS: Serum PSA levels were positively correlated
      to prostate weight (r = 0.515, P = 0.025) and age (r = 0.548, P = 0.00072) but
      was not significantly correlated to body weight (r = -0.032, P = 0.419). For the
      animals on the HSHF diet, body weight, lean mass, fat mass, and BMI were
      significantly higher at 49 weeks than at baseline (P < 0.01). PSA was not
      significantly correlated to body weight and insulin at both baseline and 49
      weeks. PSA was negatively correlated to BMI and insulin resistance (HOMA-IR) at
      49 weeks but not at baseline. In addition, we observed hepatic steatosis and
      increases in serum liver enzymes. CONCLUSIONS: Increases in BMI in cynomolgus
      monkeys as a result of consuming a HSHF diet resulted in PSA changes similar to
      those in humans with increased BMI. Cynomolgus monkeys are a useful model for
      investigating the relationship between obesity, diabetes, and PSA changes
      resulting from prostate gland pathology.

PMID- 21713966
TI  - A case study of model-based Bayesian dose response estimation.
AB  - A Bayesian nonlinear longitudinal Emax model for a binary endpoint was used to
      characterize the dose-response relationship for a new treatment of rheumatoid
      arthritis. The model includes prespecified parametric functions for the
      dependence of response on dose level and time. It was selected based on
      pharmacometric input about likely dose and time trends. The longitudinal model
      was useful for combining data collected at different doses and times from two
      different studies. The example illustrates the utility of more substantive
      parametric models to guide selection of doses outside the initial dosing range
      when designing an additional phase 2 study and for extrapolating shorter-term
      phase 2 dose response to longer-term phase 3 studies, as is often required for
      dosing decisions in drug development for chronic diseases. Comparison of the
      estimated dose response from the longitudinal model with a corresponding logistic
      regression model applied at a single time point also demonstrated improved
      precision. Specification of an informative prior distribution based on numerous
      sources of prior information is described. This was the most difficult step in
      the analysis and one that has limited the use of Bayesian methods in similar
      applications. Model fit was evaluated and the potential impact of some model
      deficiencies on the dosing decision was assessed. Analyses of the combined
      studies identified doses likely to achieve a targeted effect in larger and longer
      confirmatory trials.

PMID- 21713967
TI  - 1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-pyrrolidine-2
      carboxamide: investigation of structural variations.
AB  - We recently reported a series of 1-acyl-N-(biphenyl-4-ylmethyl)pyrrolidine-2
      carboxamides as AT(1) receptor ligands. The most potent compound of the series, 1
      pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-pyrrolidine-2
      carboxamide, showed an interesting affinity for the receptor. To investigate the
      influence of structure variations on affinity, the synthesis of additional
      compounds belonging to this series has been performed. Biological tests run on
      the newly synthesized compounds on CHO-hAT(1) cells stably expressing the human
      AT(1) receptor confirm our previous hypothesis, i.e. that, within this series,
      the length of the acyl chain, the substitution of the amidic group and the nature
      of the acidic one are crucial for the receptor interaction, being a valeric
      chain, a secondary amidic function and the tetrazole moiety, respectively, the
      optimal ones.

PMID- 21713968
TI  - Coupling of methylmercury uptake with respiration and water pumping in freshwater
      tilapia Oreochromis niloticus.
AB  - The relationships among the uptake of toxic methylmercury (MeHg) and two
      important fish physiological processes-respiration and water pumping--in the Nile
      tilapia (Oreochromis niloticus) were explored in the present study. Coupled
      radiotracer and respirometric techniques were applied to measure simultaneously
      the uptake rates of MeHg, water, and oxygen under various environmental
      conditions (temperature, dissolved oxygen level, and water flow). A higher
      temperature enhanced MeHg influx and the oxygen consumption rate but had no
      effect on the water uptake, indicating the influence of metabolism on MeHg
      uptake. The fish showed a high tolerance to hypoxia, and the oxygen consumption
      rate was not affected until the dissolved oxygen concentration decreased to
      extremely low levels (below 1 mg/L). The MeHg and water uptake rates increased
      simultaneously as the dissolved oxygen level decreased, suggesting the coupling
      of water flux and MeHg uptake. The influence of fish swimming performance on MeHg
      uptake was also investigated for the first time. Rapidly swimming fish showed
      significantly higher uptake rates of MeHg, water, and oxygen, confirming the
      coupling relationships among respiration, water pumping, and metal uptake.
      Moreover, these results support that MeHg uptake is a rate-limiting process
      involving energy. Our study demonstrates the importance of physiological
      processes in understanding mercury bioaccumulation in fluctuating aquatic
      environments.

PMID- 21713969
TI  - Mobility and contamination assessment of mercury in coal fly ash, atmospheric
      deposition, and soil collected from Tianjin, China.
AB  - Samples of class F coal fly ash (levels I, II, and III), slag, coal, atmospheric
      deposition, and soils collected from Tianjin, China, were analyzed using U.S.
      Environmental Protection Agency (U.S. EPA) Method 3052 and a sequential
      extraction procedure, to investigate the pollution status and mobility of Hg. The
      results showed that total mercury (HgT) concentrations were higher in level I fly
      ash (0.304 ug/g) than in level II and level III fly ash and slag (0.142, 0.147,
      and 0.052 ug/g, respectively). Total Hg in the atmospheric deposition was higher
      during the heating season (0.264 ug/g) than the nonheating season (0.135 ug/g).
      Total Hg contents were higher in suburban area soils than in rural and
      agricultural areas. High HgT concentrations in suburban area soils may be a
      result of the deposition of Hg associated with particles emitted from coal-fired
      power plants. Mercury in fly ash primarily existed as elemental Hg, which
      accounted for 90.1, 85.3, and 90.6% of HgT in levels I, II, and III fly ash,
      respectively. Mercury in the deposition existed primarily as sulfide Hg, which
      accounted for 73.8% (heating season) and 74.1% (nonheating season) of HgT.
      However, Hg in soils existed primarily as sulfide Hg, organo-chelated Hg and
      elemental Hg, which accounted for 37.8 to 50.0%, 31.7 to 41.8%, and 13.0 to 23.9%
      of HgT, respectively. The percentage of elemental Hg in HgT occurred in the order
      fly ash > atmospheric deposition > soils, whereas organo-chelated Hg and sulfide
      Hg occurred in the opposite order. The present approach can provide a window for
      understanding and tracing the source of Hg in the environment in Tianjin and the
      risk associated with Hg bioaccessibility.

PMID- 21713970
TI  - Critical load analysis in hazard assessment of metals using a Unit World Model.
AB  - A Unit World approach has been used extensively to rank chemicals for their
      hazards and to understand differences in chemical behavior. Whereas the fate and
      effects of an organic chemical in a Unit World Model (UWM) analysis vary
      systematically according to one variable (fraction of organic carbon), and the
      chemicals have a singular ranking regardless of environmental characteristics,
      metals can change their hazard ranking according to freshwater chemistry, notably
      pH and dissolved organic carbon (DOC). Consequently, developing a UWM approach
      for metals requires selecting a series of representative freshwater chemistries,
      based on an understanding of the sensitivity of model results to this chemistry.
      Here we analyze results from a UWM for metals with the goal of informing the
      selection of appropriate freshwater chemistries for a UWM. The UWM loosely
      couples the biotic ligand model (BLM) to a geochemical speciation model
      (Windermere Humic Adsorption Model [WHAM]) and then to the multi-species fate
      transport-speciation (Transpec) model. The UWM is applied to estimate the
      critical load (CL) of cationic metals Cd, Cu, Ni, Pb, and Zn, using three lake
      chemistries that vary in trophic status, pH, and other parameters. The model
      results indicated a difference of four orders of magnitude in particle-to-total
      dissolved partitioning (K(d)) that translated into minimal differences in fate
      because of the short water residence time used. However, a maximum 300-fold
      difference was calculated in Cu toxicity among the three chemistries and three
      aquatic organisms. Critical loads were lowest (greatest hazard) in the
      oligotrophic water chemistry and highest (least hazard) in the eutrophic water
      chemistry, despite the highest fraction of free metal ion as a function of total
      metal occurring in the mesotrophic system, where toxicity was ameliorated by
      competing cations. Water hardness, DOC, and pH had the greatest influence on CL,
      because of the influence of these factors on aquatic toxicity.

PMID- 21713971
TI  - Products of polycyclic aromatic sulfur heterocycles in oil spill
      photodegradation.
AB  - Photo-oxidation is a potentially significant process in the degradation of crude
      oil spilled in the environment. The polycyclic aromatic sulfur heterocycles
      (PASHs) in an Egyptian crude oil (0.8 % sulfur) were photo-oxidized as a film on
      the surface of water in the presence of anthraquinone as photosensitizer under
      simulated solar irradiation. The polar photoproducts were characterized using
      negative ion electrospray ionization with time of flight mass spectrometry and,
      after trimethylsilylation, gas chromatography with mass spectrometry. The
      photoproducts identified revealed the presence of a large variety of sulfonic
      acids, aliphatic and aromatic acids, and alcohols. The data also give new
      information on the substituents of the aromatic compounds in the unexposed oil
      and indicate the presence of cyclohexyl substituted aromatic compounds.

PMID- 21713972
TI  - Aquatic to terrestrial transfer of sediment associated persistent organic
      pollutants is enhanced by bioamplification processes.
AB  - Ephemeral emergent insects, such as mayflies (Hexagenia spp.), are commonly used
      as biomonitors of persistent organic pollutants (POPs) and provide a vector for
      aquatic-terrestrial contaminant transfer. Mayflies bioaccumulate sediment
      associated contaminants by bioconcentration and biomagnification during the
      aquatic stage and concentrate POP residues postemergence due to bioamplification,
      which occurs as a result of weight and lipid loss without contaminant loss. The
      present study quantified polychlorinated biphenyl (PCB) bioamplification in male
      and female emergent mayflies at three sites. Male mayflies used 36 to 68% of
      their lipids during emergence, with the exception of caged males that were
      prevented from flight. Females did not lose lipid content between pre-emergent
      nymph and emerged life stages. Mass balance indicated no PCB elimination between
      life stages. The mean PCB bioamplification factor, expressed as the ratio of
      lipid-equivalent PCB concentrations across life stages, was 2.05 +/- 0.38 for
      male imagos/nymphs and 1.91 +/- 0.18 for male imago/subimago life stages. For
      females, bioamplification factors were close to unity. Wildlife consumers of
      imago stages of emergent mayflies can potentially increase their total daily
      intake of PCBs by 36% depending on the sex-ratio composition of their diet
      relative to animals that feed predominantly on nymph or subimago stages during
      mass emergence events.

PMID- 21713973
TI  - Enzymatic correlates of energy status in wild yellow perch inhabiting clean and
      contaminated environments.
AB  - Enzymes representing a variety of metabolic pathways were examined in yellow
      perch (Perca flavescens) collected from a metal-contaminated region (Rouyn
      Noranda, Quebec, Canada) to determine which were most closely related to fish
      condition factor, pyloric caeca weight, and visceral lipid accumulation, as well
      to seek a better understanding of the influence of metal contamination on the
      physiology and biometrics of perch. Compared to laboratory fish, wild perch were
      under important energy restrictions. The condition factor of wild fish was
      correlated with indicators of aerobic metabolism (citrate synthase, cytochrome C
      oxidase), protein anabolism (nucleoside diphosphokinase), and indicators of lipid
      accumulation (glucose-6-phosphate dehydrogenase, visceral lipid index). Pyloric
      caeca weights were well correlated with indicators of protein anabolism, but only
      when both seasons were examined together, possibly indicating a lag in the
      response of enzymes to changes in diet. The addition of contaminant stress to
      existing energy restrictions led to changes in the relationships between enzymes
      and biometrics, reducing the predictive power of the models for perch in
      contaminated lakes. The present study broadens our knowledge of the impact of
      metal contamination on energy accumulation and tissue metabolic capacities in
      wild perch.

PMID- 21713974
TI  - Avoidance of lip split: a response.

PMID- 21713975
TI  - Functional pectoralis minor muscle flap transplantation for reconstruction of
      thumb opposition: an anatomic study and clinical applications.
AB  - In this report, we present the results of an anatomic study on the dimensions of
      the pectoralis minor muscle and its neurovascular supply in 10 adult human
      cadavers, in attempt to evaluate the feasibility of microsurgical transplantation
      of a part of the muscle for thumb opposition reconstruction. A series of five
      patients consequently underwent thenar reconstruction with the pectoralis minor
      muscle flap from December 2004 to October 2006. The transferred muscle was
      reinnervated with the third lumbrical branch of the ulnar nerve. Follow-up
      assessment showed that the patients recovered functional opposition of
      carpometacarpal joint with 24 degrees of pronation, and a muscle power with M4 to
      M5. All patients were satisfied with the appearance of reconstructed thenar
      eminence. We recommend this new technique for thenar and opposition
      reconstruction in patients who have severe loss of thenar muscles, injury to the
      median nerve, and wish to improve the appearance of thenar eminence.

PMID- 21713976
TI  - Parallel imaging with asymmetric acceleration to reduce Gibbs artifacts and to
      increase signal-to-noise ratio of the gradient echo echo-planar imaging sequence
      for functional MRI.
AB  - Parallel imaging with accelerated acquisition was noted to pronounce Gibbs
      artifacts which appear as ripples propagated in the phase-encoding (PE) direction
      near the susceptibility-affected region in echo-planar imaging (EPI). Using the
      extended EPI sequence, which collected extended readouts outside the regular data
      sampling time, the pronounced Gibbs artifact was analyzed and found to be caused
      by an increased echo shift in the pre-echo time (T(E)) of accelerated parallel
      imaging. This was also confirmed by theoretical derivation of the echo shift
      caused by the inplane susceptibility gradient in the PE direction (ISG(PE)). A
      new EPI sequence was developed to reduce the Gibbs artifact and to restore the
      signal level toward that of nonaccelerated parallel imaging by asymmetrically
      accelerating only the post-T(E) sampling time and by using the extended EPI in
      the pre-T(E). The nonaccelerated portion in the pre-T(E) used the delay for the
      optimum blood oxygen level dependent (BOLD) sensitivity at 3 T, maintaining the
      same slice coverage as the symmetrical acceleration in both pre-T(E) and post
      T(E). The increased data sampling points resulted in an increase of the signal-to
      noise ratio (SNR). The restored signal and enhanced SNR of the proposed method
      were confirmed to deliver a better BOLD functional MRI (fMRI) result in the
      breath holding experiment.

PMID- 21713977
TI  - Non-contrast-enhanced vascular magnetic resonance imaging using flow-dependent
      preparation with subtraction.
AB  - Recent concerns over contrast agent safety have encouraged new developments in
      non-contrast-enhanced vascular imaging techniques. This work investigates the
      potential for imaging both arteries and veins with vascular anatomy by
      nonenhanced static subtraction angiography (VANESSA), a method using controllable
      flow suppression together with subtraction of bright- and dark-blood images. The
      lower legs of eight healthy volunteers and three patients were imaged using a
      modified motion-sensitized driven equilibrium preparation, with three-dimensional
      balanced steady-state free precession readout. The vascular signal decreased with
      increasing motion-suppression gradient amplitude, and was suppressed when the
      velocity-encoding parameter was (approximately) less than the measured flow
      velocity. Selected pairs of images were subtracted to depict vessels with either
      fast flow (e.g. arteries), slow flow (e.g. veins), or both. Several
      methodological modifications improved image quality and reduced the background
      signal from static tissues. Subjectively assessed image quality in volunteers was
      rated as excellent for 56/64 arterial segments, and good or excellent for 35/64
      veins. In conclusion, VANESSA enables rapid non-contrast-enhanced imaging of
      arteries and veins, combining information on both morphology and flow. This study
      demonstrates good technical performance in volunteers and evaluation in patients
      with vascular disease is warranted.

PMID- 21713978
TI  - Addressing phase errors in fat-water imaging using a mixed magnitude/complex
      fitting method.
AB  - Accurate, noninvasive measurements of liver fat content are needed for the early
      diagnosis and quantitative staging of nonalcoholic fatty liver disease. Chemical
      shift-based fat quantification methods acquire images at multiple echo times
      using a multiecho spoiled gradient echo sequence, and provide fat fraction
      measurements through postprocessing. However, phase errors, such as those caused
      by eddy currents, can adversely affect fat quantification. These phase errors are
      typically most significant at the first echo of the echo train, and introduce
      bias in complex-based fat quantification techniques. These errors can be overcome
      using a magnitude-based technique (where the phase of all echoes is discarded),
      but at the cost of significantly degraded signal-to-noise ratio, particularly for
      certain choices of echo time combinations. In this work, we develop a
      reconstruction method that overcomes these phase errors without the signal-to
      noise ratio penalty incurred by magnitude fitting. This method discards the phase
      of the first echo (which is often corrupted) while maintaining the phase of the
      remaining echoes (where phase is unaltered). We test the proposed method on 104
      patient liver datasets (from 52 patients, each scanned twice), where the fat
      fraction measurements are compared to coregistered spectroscopy measurements. We
      demonstrate that mixed fitting is able to provide accurate fat fraction
      measurements with high signal-to-noise ratio and low bias over a wide choice of
      echo combinations.

PMID- 21713979
TI  - Localized blood flow imaging using quantitative flow-enhanced signal intensity.
AB  - Flow-enhanced signal intensity (FENSI) was previously introduced as a novel
      functional imaging method for measuring changes in localized blood flow in
      response to a stimulus. However, FENSI was limited to a qualitative functional
      MRI tool, due to magnetization transfer effects and different tagging plane
      profiles between tag and control images. In this work, a revised FENSI
      acquisition is proposed to enable quantitative imaging, which is capable of
      providing absolute localized blood flow maps free from magnetization transfer and
      slice profile errors. The feasibility and accuracy of measuring microvascular
      (arteriole, capillary, and venule) blood flow by using quantitative FENSI was
      validated by our phantom studies. Additionally, localized cerebral blood flow,
      366 +/- 45 MUL/min/cm(2) in gray matter and 153 +/- 23 MUL/min/cm(2) in white
      matter, was measured in healthy subjects during resting state, whereas a flow
      change of 73 +/- 13% was detected during a visual task.

PMID- 21713980
TI  - A hybrid method for more efficient channel-by-channel reconstruction with many
      channels.
AB  - In MRI, imaging using receiving coil arrays with a large number of elements is an
      area of growing interest. With increasing channel numbers for parallel
      acquisition, longer reconstruction times have become a significant concern.
      Channel reduction techniques have been proposed to reduce the processing time of
      channel-by-channel reconstruction algorithms. In this article, two schemes are
      combined to enable faster and more accurate reconstruction than existing channel
      reduction techniques. One scheme use two stages of channel reduction instead of
      one. The other scheme is to incorporate all acquired data into the final
      reconstruction. The combination of these two schemes is called flexible virtual
      coil. Applications of flexible virtual coil for partially parallel imaging,
      motion compensation, and compressed sensing are presented as specific examples.
      Theoretical analysis and experimental results demonstrate that the proposed
      method has a major impact in reducing computation cost in reconstruction with
      high-channel count coil elements.

PMID- 21713981
TI  - Phase-based regional oxygen metabolism (PROM) using MRI.
AB  - Venous oxygen saturation (Y(v) ) in cerebral veins and the cerebral metabolic
      rate of oxygen (CMRO(2)) are important indicators for brain function and disease.
      Although MRI has been used for global measurements of these parameters, currently
      there is no recognized technique to quantify regional Y(v) and CMRO(2) using
      noninvasive imaging. This article proposes a technique to quantify CMRO(2) from
      independent MRI estimates of Y(v) and cerebral blood flow. The approach uses
      standard gradient-echo and arterial spin labeling acquisitions to make these
      measurements. Using MR susceptometry on gradient-echo phase images, Y(v) was
      quantified for candidate vein segments in gray matter that approximate a long
      cylinder parallel to the main magnetic field. Local cerebral blood flow for the
      identified vessel was determined from a corresponding region in the arterial spin
      labeling perfusion map. Fick's principle of arteriovenous difference was then
      used to quantify CMRO(2) locally around each vessel. Application of this method
      in young, healthy subjects provided gray matter averages of 59.6% +/- 2.3% for
      Y(v), 51.7 +/- 6.4 mL/100 g/min for cerebral blood flow, and 158 +/- 18 MUmol/100
      g/min for CMRO(2) (mean +/- SD, n = 12), which is consistent with values
      previously reported by positron emission tomography and MRI.

PMID- 21713982
TI  - Rapid B1 mapping using orthogonal, equal-amplitude radio-frequency pulses.
AB  - We present a new phase-based method for mapping the amplitude of the radio
      frequency field (B(1) ) of a transmitter coil in three-dimension. This method
      exploits the noncommutation relation between rotations about orthogonal axes. Our
      implementation of this principle in the current work results in a simple relation
      between the phase of the final magnetization and the flip angle (FA). In this
      study, we focus on FAs less than 90 degrees . Our method is rapid and easy to
      implement compared with the existing B(1) mapping schemes. The mapping sequence
      can be simply obtained by adding to a regular three-dimensional gradient-echo
      sequence a magnetization preparation radio-frequency pulse of the same FA but
      orthogonal in phase to the excitation radio-frequency pulse. This method is
      demonstrated capable of generating reliable maps of the B(1) field within 1 min
      using FAs no larger than 60 degrees . We show that it is robust against T(1),
      small chemical shift, and mild background inhomogeneity. This method may
      especially be suitable for B(1) mapping in situations (e.g., long-T(1) and
      hyperpolarized-gas imaging) where magnitude-based methods are not readily
      applicable. A noise calculation of the FA map using this method is also
      presented.

PMID- 21713983
TI  - Accelerated water-fat imaging using restricted subspace field map estimation and
      compressed sensing.
AB  - Water-fat separation techniques play an important role in a variety of clinical
      and research applications. In particular, multiecho separation methods remain a
      topic of great interest due to their ability to resolve water and fat images in
      the presence of B(0)-field inhomogeneity. However, these methods are inherently
      slow as they require multiple measurements. An accelerated technique with reduced
      k-space sampling is desirable to decrease the scan time. This work presents a new
      method for water-fat separation from accelerated multiecho acquisitions. The
      proposed approach does not require the region-growing or region-merging schemes
      that are typically used for field map estimation. Instead, the water, fat, and
      field map signals are estimated directly from the undersampled k-space
      measurements. In this work, up to 2.5*-acceleration is demonstrated in a water
      fat phantom, ankle, knee, and liver.

PMID- 21713984
TI  - Effect of intercompartmental water exchange on the apparent myelin water fraction
      in multiexponential T2 measurements of rat spinal cord.
AB  - The myelin water fraction has been used as a quantitative measure of the amount
      of myelin present in tissue. However, recent work has suggested that
      intercompartmental exchange of water between myelin and nonmyelin compartments
      may cause the myelin water fraction to underestimate the true myelin content of
      tissue. In this work, multiexponential T(2) experiments were performed in vivo
      within the rat spinal cord, and a wide variation of the myelin water fraction (10
      35%) was measured within four rat spinal cord tracts with similar myelin content.
      A numerical simulation based upon segmented histology images was used to
      quantitatively account for T(2) variations between tracts. The model predicts
      that a difference in exchange between the four spinal cord tracts, mediated by a
      difference in the average axon radius and myelin thickness, is sufficient to
      account for the variation in myelin water fraction measured in vivo.

PMID- 21713985
TI  - Lung morphometry with hyperpolarized 129Xe: theoretical background.
AB  - The (3) He lung morphometry technique, based on MRI measurements of
      hyperpolarized (3) He gas diffusion in lung airspaces, provides unique
      information on the lung microstructure at the alveolar level. In vivo 3D
      tomographic images of standard morphological parameters (airspace chord length,
      lung parenchyma surface-to-volume ratio, and number of alveoli per unit volume)
      can be generated from a rather short (several seconds) MRI scan. The technique is
      based on a theory of gas diffusion in lung acinar airways and experimental
      measurements of diffusion-attenuated MRI signal. The present work aims at
      developing the theoretical background of a similar technique based on
      hyperpolarized (129) Xe gas. As the diffusion coefficient and gyromagnetic ratio
      of (129) Xe gas are substantially different from those of (3) He gas, the
      specific details of the theory and experimental measurements with (129) Xe should
      be amended. We establish phenomenological relationships between acinar airway
      geometrical parameters and the diffusion-attenuated MR signal for human and small
      animal lungs, both normal lungs and lungs with mild emphysema. Optimal diffusion
      times are shown to be about 5 ms for human and 1.3 ms for small animals. The
      expected uncertainties in measuring main morphometrical parameters of the lungs
      are estimated in the framework of Bayesian probability theory.

PMID- 21713986
TI  - Impact of oncopediatric dosing regimen of zoledronic acid on bone growth:
      preclinical studies and case report of an osteosarcoma pediatric patient.
AB  - Osteosarcoma and Ewing sarcoma represent the two most frequent primary bone
      tumors that arise in the pediatric population. Despite recent improvement in
      their therapeutic management, no improvement in survival rate has been achieved
      since early 1980 s. Among new therapeutic approaches, bisphosphonates are
      promising candidates as potent inhibitors of bone resorption. However, their
      effects on bone growth must be studied at dosing regimen corresponding to
      pediatric protocols. To this aim, several protocols using zoledronic acid (ZOL)
      were developed in growing mice (50 ug/kg every 2 days * 10). Parameters of bone
      remodeling and bone growth were investigated by radiography, micro-computed
      tomography, histology, and biologic analyses. Extramedullar hematopoiesis was
      searched for in spleen tissue. A transient inhibitory effect of ZOL was observed
      on bone length, with a bone-growth arrest during treatment owing to an impressive
      increase in bone formation at the growth plate level (8- to 10-fold increase in
      BV/TV). This sclerotic band then shifted into the diaphysis as soon as
      endochondral bone formation started again after the end of ZOL treatment,
      revealing that osteoclasts and osteoblasts are still active at the growth plate.
      In conclusion, endochondral bone growth is transiently disturbed by high doses of
      ZOL corresponding to the pediatric treatment of primary bone tumors. These
      preclinical observations were confirmed by a case report in a pediatric patient
      treated in the French OS2006 protocol over 10 months who showed a growth arrest
      during the ZOL treatment period with normal gain in size after the end of
      treatment.

PMID- 21713987
TI  - Hypophosphatasia: nonlethal disease despite skeletal presentation in utero (17
      new cases and literature review).
AB  - Hypophosphatasia (HPP) is caused by deactivating mutation(s) within the gene that
      encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP).
      Patients manifest rickets or osteomalacia and dental disease ranging from absence
      of skeletal mineralization in utero to only loss of adult dentition. Until
      recently, HPP skeletal disease in utero was thought to always predict a lethal
      outcome. However, several reports beginning in 1999 emphasized a benign prenatal
      form of HPP (BP-HPP) where skeletal disease detected in utero had a mild
      postnatal course. Here we describe prenatal and postnatal findings of 17
      additional BP-HPP patients among our 178 pediatric HPP patients. Their findings
      are compared with those of their siblings with HPP, carrier parents, and others
      with identical TNSALP mutations. New information concerning 7 previously
      published BP-HPP patients accompanies a review of the HPP literature. Among our
      17 BP-HPP patients, prenatal ultrasound showed normal chest or abdominal
      circumferences where recorded. Sometimes, poor skeletal mineralization, fetal
      crowding, and third-trimester improvement were observed. Postnatally, extremity
      bowing further improved (13 patients). BP-HPP severity postnatally spanned the
      "infantile" to "odonto" HPP phenotypes, resembling our patients who harbored
      identical TNSALP mutation(s). Eight had autosomal dominant (AD) and 9 had
      autosomal recessive (AR) BP-HPP. Fourteen of our 15 mothers were HPP carriers or
      affected. Of the 41 cumulative BP-HPP patients (24 literature cases meriting a BP
      HPP diagnosis since 1996 plus our 17 patients), 63% had AR BP-HPP. Maternally
      transmitted HPP involved 11 of the 13 total AD BP-HPP probands (p = 0.01),
      supporting a maternal in utero effect on the baby. Fetal crowding, normal fetal
      mineralization and chest size, and TNSALP heterozygosity seem to identify BP-HPP.
      However, bowed fetal long bones with AR HPP, specific TNSALP mutations, or poor
      skeletal mineralization before the third trimester do not reliably diagnose HPP
      lethality.

PMID- 21713988
TI  - Formulated siRNAs targeting Rankl prevent osteolysis and enhance chemotherapeutic
      response in osteosarcoma models.
AB  - The development of osteosarcoma, the most common malignant primary bone tumor is
      characterized by a vicious cycle established between tumor proliferation and
      paratumor osteolysis. This osteolysis is mainly regulated by the receptor
      activator of nuclear factor kappaB ligand (RANKL). Preclinical studies have
      demonstrated that Rankl blockade by soluble receptors is an effective strategy to
      prevent osteolytic lesions leading to osteosarcoma inhibition. A new therapeutic
      option could be to directly inhibit Rankl expression by small interfering RNAs
      (Rkl-siRNAs) and combine these molecules with chemotherapy to counteract the
      osteosarcoma development more efficiently. An efficient siRNA sequence directed
      against both mouse and rat mRNAs coding Rankl was first validated in vitro and
      tested in two models of osteosarcoma: a syngenic osteolytic POS-1 model induced
      in immunocompetent mice and a xenograft osteocondensant model of rat OSRGA in
      athymic mice. Intratumor injections of Rankl-directed siRNAs in combination with
      the cationic liposome RPR209120/DOPE reduced the local and systemic Rankl
      production and protected bone from paratumor osteolysis. Although Rkl-siRNAs
      alone had no effect on tumor development in both osteosarcoma models, it
      significantly blocked tumor progression when combined with ifosfamide compared
      with chemotherapy alone. Our results indicate that siRNAs could be delivered
      using cationic liposomes and thereby could inhibit Rankl production in a specific
      manner in osteosarcoma models. Moreover, the Rankl inhibition mediated by RNA
      interference strategy improves the therapeutic response of primary osteosarcoma
      to chemotherapy.

PMID- 21713989
TI  - Direct costs of fractures in Canada and trends 1996-2006: a population-based cost
      of-illness analysis.
AB  - Cost-of-illness (COI) analysis is used to evaluate the economic burden of illness
      in terms of health care resource (HCR) consumption. We used the Population Health
      Research Data Repository for Manitoba, Canada, to identify HCR costs associated
      with 33,887 fracture cases (22,953 women and 10,934 men) aged 50 years and older
      that occurred over a 10-year period (1996-2006) and 101,661 matched control
      individuals (68,859 women and 32,802 men). Costs (in 2006 Canadian dollars) were
      estimated for the year before and after fracture, and the change (incremental
      cost) was modeled using quantile regression analysis to adjust for baseline
      covariates and to study temporal trends. The greatest total incremental costs
      were associated with hip fractures (median $16,171 in women and $13,111 for men),
      followed by spine fractures ($8,345 in women and $6,267 in men). The lowest costs
      were associated with wrist fractures ($663 in women and $764 in men). Costs for
      all fracture types were greater in older individuals (p < 0.001). Similar results
      were obtained with regression-based adjustment for baseline factors. Some costs
      showed a slight increase over the 10 years. The largest temporal increase in
      women was for hip fracture ($13 per year, 95% CI $6-$21, p < 0.001) and in men
      was for humerus fracture ($11 per year, 95% CI $3-$19, p = 0.007). At the
      population level, hip fractures were responsible for the largest proportion of
      the costs after age 80, but the other fractures were more important prior to age
      80. We found that there are large incremental health care costs associated with
      incident fractures in Canada. Identifying COI from HCR use offers a cost baseline
      for measuring the effects of evidence-based guidelines implementation.

PMID- 21713990
TI  - Universal cervical-length screening and vaginal progesterone prevents early
      preterm births, reduces neonatal morbidity and is cost saving: doing nothing is
      no longer an option.

PMID- 21713991
TI  - Allantoic cysts and posterior urethral valves: a case report.
AB  - Allantoic cysts are a somewhat rare entity. They are identifiable on antenatal
      ultrasound examination but are not easily distinguishable from pseudocysts, which
      are often associated with a poor prognosis. Their etiology remains obscure and
      obstructive uropathies have been proposed to be one of the underlying mechanisms.
      We report on a case in which both allantoic cysts and a patent urachus were
      detected antenatally and turned out to be associated with posterior urethral
      valves (PUV). The cysts were first seen in the early second trimester, with a
      full fetal bladder and patent urachus. They disappeared by the 29(th) week.
      During the subsequent sonographic examinations, the bladder was emptying
      regularly. The kidneys remained normal throughout the pregnancy. It is
      hypothesized that the increased pressure within the urinary tract kept the
      urachus patent, led to the formation of allantoic cysts and, later, to their
      perforation; this allowed the fetus to empty his bladder and kept him from the
      usual complications of PUV. This case emphasizes the importance of detection and
      characterization of umbilical cord cysts on antenatal ultasound examination and
      suggests that obstructive uropathies should be included in the differential
      diagnosis of umbilical cord cyst communicating with the fetal bladder.

PMID- 21713993
TI  - MafB interacts with Gcm2 and regulates parathyroid hormone expression and
      parathyroid development.
AB  - Serum calcium and phosphate homeostasis is critically regulated by parathyroid
      hormone (PTH) secreted by the parathyroid glands. Parathyroid glands develop from
      the bilateral parathyroid-thymus common primordia. In mice, the expression of
      transcription factor Glial cell missing 2 (Gcm2) begins in the dorsal/anterior
      part of the primordium on embryonic day 9.5 (E9.5), specifying the parathyroid
      domain. The parathyroid primordium then separates from the thymus primordium and
      migrates to its adult location beside the thyroid gland by E15.5. Genetic
      ablation of gcm2 results in parathyroid agenesis in mice, indicating that Gcm2 is
      essential for early parathyroid organogenesis. However, the regulation of
      parathyroid development at later stages is not well understood. Here we show that
      transcriptional activator v-maf musculoaponeurotic fibrosarcoma oncogene
      homologue B (MafB) is developmentally expressed in parathyroid cells after E11.5.
      MafB expression was lost in the parathyroid primordium of gcm2 null mice. The
      parathyroid glands of mafB(+/-) mice were mislocalized between the thymus and
      thyroid. In mafB(-/-) mice, the parathyroid did not separate from the thymus.
      Furthermore, in mafB(-/-) mice, PTH expression and secretion were impaired;
      expression levels of renal cyp27b1, one of the target genes of PTH, was
      decreased; and bone mineralization was reduced. We also demonstrate that although
      Gcm2 alone does not stimulate the PTH gene promoter, it associates with MafB to
      synergistically activate PTH expression. Taken together, our results suggest that
      MafB regulates later steps of parathyroid development, that is, separation from
      the thymus and migration toward the thyroid. MafB also regulates the expression
      of PTH in cooperation with Gcm2.

PMID- 21713994
TI  - Intermittent PTH(1-84) is osteoanabolic but not osteoangiogenic and relocates
      bone marrow blood vessels closer to bone-forming sites.
AB  - Intermittent parathyroid hormone (PTH) is anabolic for bone. Our aims were to
      determine (1) whether PTH stimulates bone angiogenesis and (2) whether vascular
      endothelial growth factor (VEGF A) mediates PTH-induced bone accrual. Male Wistar
      rats were given PTH(1-84) daily, and trabecular bone mass increased 150% and 92%
      after 30 and 15 days, respectively. The vascular system was contrasted to image
      and quantify bone vessels with synchrotron radiation microtomography and
      histology. Surprisingly, bone vessel number was reduced by approximately 25% and
      approximately 40% on days 30 and 15, respectively. PTH redistributed the smaller
      vessels closer to bone-formation sites. VEGF A mRNA expression in bone was
      increased 2 and 6 hours after a single dose of PTH and returned to baseline by 24
      hours. Moreover, anti-VEGF antibody administration (1) blunted the PTH-induced
      increase in bone mass and remodeling parameters, (2) prevented the relocation of
      bone vessels closer to bone-forming sites, and (3) inhibited the PTH-induced
      increase in mRNA of neuropilin 1 and 2, two VEGF coreceptors associated with
      vascular development and function. In conclusion, PTH(1-84) is osteoanabolic
      through VEGF-related mechanism(s). Further, PTH spatially relocates blood vessels
      closer to sites of new bone formation, which may provide a microenvironment
      favorable for growth.

PMID- 21713995
TI  - Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating
      RUNX2 gene expression via the SIRT1/FOXO3A axis.
AB  - Reports of the bone-protective effects of resveratrol, a naturally occurring
      phytoestrogen and agonist for the longevity gene SIRT1, have highlighted this
      compound as a candidate for therapy of osteoporosis. Moreover, SIRT1 antagonism
      enhances adipogenesis. There has been speculation that resveratrol can promote
      osteogenesis through SIRT1, but the mechanism remains unclear. In this study we
      investigated the molecular mechanism of how resveratrol can modulate the lineage
      commitment of human mesenchymal stem cells to osteogenesis other than
      adipogenesis. We found that resveratrol promoted spontaneous osteogenesis but
      prevented adipogenesis in human embryonic stem cell-derived mesenchymal
      progenitors. Resveratrol upregulated the expression of osteo-lineage genes RUNX2
      and osteocalcin while suppressing adipo-lineage genes PPARgamma2 and LEPTIN in
      adipogenic medium. Furthermore, we found that the osteogenic effect of
      resveratrol was mediated mainly through SIRT1/FOXO3A with a smaller contribution
      from the estrogenic pathway. Resveratrol activated SIRT1 activity and enhanced
      FOXO3A protein expression, a known target of SIRT1, in an independent manner. As
      a result, resveratrol increased the amount of the SIRT1-FOXO3A complex and
      enhanced FOXO3A-dependent transcriptional activity. Ectopic overexpression or
      silencing of SIRT1/FOXO3A expression regulated RUNX2 promoter activity,
      suggesting an important role for SIRT1-FOXO3A complex in regulating resveratrol
      induced RUNX2 gene transcription. Further mutational RUNX2 promoter analysis and
      chromatin immunoprecipitation assay revealed that resveratrol-induced SIRT1
      FOXO3A complex bound to a distal FOXO response element (-1269/-1263), an action
      that transactivated RUNX2 promoter activity in vivo. Taken together, our results
      describe a novel mechanism of resveratrol in promoting osteogenesis of human
      mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A
      axis.

PMID- 21713996
TI  - Parathyroid hormone signaling via Galphas is selectively inhibited by an NH(2)
      terminally truncated Galphas: implications for pseudohypoparathyroidism.
AB  - Pseudohypoparathyroid patients have resistance predominantly to parathyroid
      hormone (PTH), and here we have examined the ability of an alternative Galphas
      related protein to inhibit Galphas activity in a hormone-selective manner. We
      tested whether the GNAS exon A/B-derived NH(2)-terminally truncated (Tr) alphas
      protein alters stimulation of adenylate cyclase by the PTH receptor (PTHR1), the
      thyroid-stimulating hormone (TSH) receptor (TSHR), the beta(2)-adrenergic
      receptor (beta(2)AR), or the AVP receptor (V2R). HEK293 cells cotransfected with
      receptor and full-length (FL) Galphas +/- Tr alphas protein expression vectors
      were stimulated with agonists (PTH [10(-7) to 10(-9)  M], TSH [1 to 100 mU],
      isoproterenol [10(-6) to 10(-8)  M], or AVP [10(-6) to 10(-8)  M]). Following PTH
      stimulation, HEK293 cells cotransfected with PTHR1 + FL Galphas + Tr alphas had a
      significantly lower cAMP response than those transfected with only PTHR1 + FL
      Galphas. Tr alphas also exerted an inhibitory effect on the cAMP levels
      stimulated by TSH via the TSHR but had little or no effect on isoproterenol or
      AVP acting via beta(2)AR or V2R, respectively. These differences mimic the
      spectrum of hormone resistance in pseudohypoparathyroidism type 1a (PHP-1a) and
      type 1b (PHP-1b) patients. In opossum kidney (OK) cells, endogenously expressing
      the PTHR1 and beta(2)AR, the exogenous expression of Tr alphas at a level similar
      to endogenous FL Galphas resulted in blunting of the cAMP response to PTH,
      whereas that to isoproterenol was unaltered. A pseudopseudohypoparathyroid
      patient with Albright hereditary osteodystrophy harbored a de novo paternally
      inherited M1I Galphas mutation. Similar maternally inherited mutations at the
      initiation codon have been identified previously in PHP-1a patients. The M1I
      alphas mutant (lacking the first 59 amino acids of Galphas) blunted the increase
      in cAMP levels stimulated via the PTHR1 in both HEK293 and OK cells similar to
      the Tr alphas protein. Thus NH(2)-terminally truncated forms of Galphas may
      contribute to the pathogenesis of pseudohypoparathyroidism by inhibiting the
      activity of Galphas itself in a GPCR selective manner.

PMID- 21713997
TI  - LRP5, serotonin, and bone: complexity, contradictions, and conundrums.

PMID- 21713998
TI  - Surgical probings into the basal ganglia: Hemorrhage and hardware-related risks,
      and costs of microelectrode recording.

PMID- 21713999
TI  - Psychiatric disorders, myoclonus dystonia, and the epsilon-sarcoglycan gene: a
      systematic review.
AB  - BACKGROUND: Mutations in the maternally imprinted epsilon-sarcoglycan gene occur
      in 30%-50% of myoclonus-dystonia cases. Psychiatric symptoms, particularly
      obsessive-compulsive disorder, have been described in some patients. METHODS: We
      systematically reviewed 22 reports of psychiatric symptoms in myoclonus-dystonia,
      dividing individuals according to clinical and mutation status. RESULTS:
      Clinically manifesting mutation carriers demonstrated an excess of psychiatric
      disorders compared with nonmutation carriers (P < .001). No differences were seen
      between non-motor-manifesting carriers and nonmutation carriers with the
      exception of alcohol excess/dependence, higher in non-motor-manifesting carriers.
      CONCLUSIONS: The results confirm the association of epsilon-sarcoglycan gene
      mutations with psychiatric disease and suggest a possible separation of the motor
      and psychiatric effects.

PMID- 21714000
TI  - Functional magnetic resonance imaging exploration of combined hand and speech
      movements in Parkinson's disease.
AB  - Among the repertoire of motor functions, although hand movement and speech
      production tasks have been investigated widely by functional neuroimaging,
      paradigms combining both movements have been studied less so. Such paradigms are
      of particular interest in Parkinson's disease, in which patients have specific
      difficulties performing two movements simultaneously. In 9 unmedicated patients
      with Parkinson's disease and 15 healthy control subjects, externally cued tasks
      (i.e., hand movement, speech production, and combined hand movement and speech
      production) were performed twice in a random order and functional magnetic
      resonance imaging detected cerebral activations, compared to the rest. F
      statistics tested within-group (significant activations at P values < 0.05,
      familywise error corrected), between-group, and between-task comparisons
      (regional activations significant at P values < 0.001, uncorrected, with cluster
      size > 10 voxels). For control subjects, the combined task activations comprised
      the sum of those obtained during hand movement and speech production performed
      separately, reflecting the neural correlates of performing movements sharing
      similar programming modalities. In patients with Parkinson's disease, only
      activations underlying hand movement were observed during the combined task. We
      interpreted this phenomenon as patients' potential inability to recruit
      facilitatory activations while performing two movements simultaneously. This lost
      capacity could be related to a functional prioritization of one movement (i.e.,
      hand movement), in comparison with the other (i.e., speech production). Our
      observation could also reflect the inability of patients with Parkinson's disease
      to intrinsically engage the motor coordination necessary to perform a combined
      task.

PMID- 21714001
TI  - Diagnosis and treatment of complications related to deep brain stimulation
      hardware.
AB  - Deep brain stimulation is a therapeutic technique increasingly used in the
      treatment of a variety of neurological, psychiatric, and pain disorders. Although
      beneficial, it carries the immediate and long-term risks associated with
      implanted hardware in the brain parenchyma and subcutaneous tissue. The most
      common hardware complications include electrode migrations or misplacements, wire
      fractures, skin erosion, infections, and device malfunction. We systematically
      reviewed the literature on deep brain stimulation-related complications and
      propose a diagnostic and therapeutic algorithm. Our aim is to provide a guide for
      clinicians and medical staff involved in the treatment of patients with deep
      brain stimulation for rapid recognition and efficient management of these
      complications.

PMID- 21714003
TI  - Kin-cohort analysis of LRRK2-G2019S penetrance in Parkinson's disease.

PMID- 21714002
TI  - Disease-related and genetic correlates of psychotic symptoms in Parkinson's
      disease.
AB  - Our aim was to examine disease-related and genetic correlates of the development
      of psychotic symptoms in a large population of patients with Parkinson's disease.
      We studied 500 patients with Parkinson's disease from the NeuroGenetics Research
      Consortium using logistic regression models. Predictors were demographic,
      clinical (motor/nonmotor features), and genetic, measured as continuous or
      dichotomous variables. Continuous measures were divided into population-based
      tertiles. Results are given as odds ratios (95% confidence intervals) for
      dichotomous variables and by ascending tertile for continuous variables.
      Psychotic symptoms were associated with increasing age: 4.86 (1.62-14.30) and
      6.25 (2.09-18.74) (test for trend: P = 0.01); and duration of disease: 3.81 (1.23
      11.76) and 5.33 (1.68-16.89) (test for trend: P = 0.03). For nonmotor features,
      we demonstrated positive trends with depression: 1.31 (0.47-3.61) and 5.01 (2.04
      12.33) (test for trend: P < 0.0001); cognitive dysfunction: 0.69 (0.26-1.84) and
      2.51 (1.00-6.29) (test for trend: P = 0.03); and an excess for those with sleep
      disorders: 2.00 (1.03-3.89) (P = 0.04). Psychotic symptoms were not associated
      with tremor or postural instability scores, but there was an association with
      freezing of gait: 3.83 (1.67-8.75) (P < 0.002). Psychotic symptoms were not
      associated with the presence of any examined polymorphisms in the apolipoprotein,
      alpha-synuclein, or microtubule associated protein tau genes. This is the largest
      study to examine correlates of psychotic symptoms in Parkinson's disease. We
      discovered a novel association with freezing of gait. We demonstrated an
      association with depression and duration of disease, both of which were
      inconsistently related in previous studies, and confirmed the association with
      age, cognitive dysfunction, and sleep disorders.

PMID- 21714004
TI  - Validation of digital spiral analysis as outcome parameter for clinical trials in
      essential tremor.
AB  - Essential tremor, one of the most prevalent movement disorders, is characterized
      by kinetic and postural tremor affecting activities of daily living. Spiral
      drawing is commonly used to visually rate tremor intensity, as part of the
      routine clinical assessment of tremor and as a tool in clinical trials. We
      present a strategy to quantify tremor severity from spirals drawn on a digitizing
      tablet. We validate our method against a well-established visual spiral rating
      method and compare both methods on their capacity to capture a therapeutic
      effect, as defined by the change in clinical essential tremor rating scale after
      an ethanol challenge. Fifty-four Archimedes spirals were drawn using a digitizing
      tablet by nine ethanol-responsive patients with essential tremor before and at
      five consecutive time points after the administration of ethanol in a
      standardized treatment intervention. Quantitative spiral tremor severity was
      estimated from the velocity tremor peak amplitude after numerical derivation and
      Fourier transformation of pen-tip positions. In randomly ordered sets, spirals
      were scored by seven trained raters, using Bain and Findley's 0 to 10 rating
      scale. Computerized scores correlated with visual ratings (P < 0.0001). The
      correlation was significant at each time point before and after ethanol (P <
      0.005). Quantitative ratings provided better sensitivity than visual rating to
      capture the effects of an ethanol challenge (P < 0.05). Using a standardized
      treatment approach, we were able to demonstrate that spirography time-series
      analysis is a valid, reliable method to document tremor intensity and a more
      sensitive measure for small effects than currently available visual spiral rating
      methods.

PMID- 21714005
TI  - Expanding the phenomenology of benign hereditary chorea: evolution from chorea to
      myoclonus and dystonia.

PMID- 21714006
TI  - Extreme task specificity in writer's cramp.
AB  - BACKGROUND: Focal hand dystonia may be task specific, as is the case with
      writer's cramp. In early stages, task specificity can be so specific that it may
      be mistaken for a psychogenic movement disorder. METHODS: We describe 4 patients
      who showed extreme task specificity in writer's cramp. They initially only had
      problems writing either a single letter or number. Although they were largely
      thought to be psychogenic, they progressed to typical writer's cramp.
      CONCLUSIONS: Early recognition of this condition may provide an opportunity for
      early initiation of treatment.

PMID- 21714007
TI  - Psychopathology and psychogenic movement disorders.
AB  - Psychogenic movement disorder is defined as abnormal movements unrelated to a
      medical cause and presumed related to underlying psychological factors. Although
      psychological factors are of both clinical and pathophysiological relevance, very
      few studies to date have systematically assessed their role in psychogenic
      movement disorder. We sought to assess the role of previous life stress using
      validated quantitative measures in patients with psychogenic movement disorder
      compared with age- and sex-matched healthy volunteers as well as a convenience
      sample of patients with focal hand dystonia. Sixty-four patients with psychogenic
      movement disorder (72% female; mean age, 45.2 years [standard deviation, 15.2
      years]), 38 healthy volunteers (74% female; mean age, 49 years [standard
      deviation, 13.7 years]), and 39 patients with focal hand dystonia (37% female;
      mean age, 48.7 years [standard deviation, 11.7 years]) were evaluated using a
      standardized psychological interview as well as validated quantitative scales to
      assess trauma and previous stressors, depression, anxiety, and personality
      traits. Patients with psychogenic movement disorder reported higher rates of
      childhood trauma, specifically greater emotional abuse and physical neglect,
      greater fear associated with traumatic events, and a greater number of traumatic
      episodes compared with healthy volunteers and patients with focal hand dystonia
      controlled for depressive symptoms and sex (Bonferroni corrected P < .005). There
      were no differences in categorical psychiatric diagnoses or scores on childhood
      physical or sexual abuse subscales, personality traits, or the dissociative
      experience scale. Our findings highlight a biopsychosocial approach toward the
      pathophysiology of psychogenic movement disorder, although the association with
      psychological issues is much less prominent than expected compared with the
      nonepileptic seizure population. A careful psychological assessment is indicated
      to optimize therapeutic modalities.

PMID- 21714008
TI  - Jejunal levodopa infusion in long-term DBS patients with Parkinson's disease.

PMID- 21714009
TI  - Increased muscle belly and tendon stiffness in patients with Parkinson's disease,
      as measured by myotonometry.
AB  - BACKGROUND: Based on Davis's law, greater tonus of the muscle belly in
      individuals with Parkinson's disease can create greater tension in the tendon,
      leading to structural adjustment and an increase in tendon stiffness. Our study
      aimed to separately assess passive stiffness in the muscle belly and tendon in
      medicated patients with Parkinson's disease, using myotonometry. METHODS: We
      tested 12 patients with Parkinson's disease and 12 healthy matched controls.
      Passive stiffness of muscle belly and tendon was estimated by myotonometry,
      electromyography, and mechanomyography in relaxed biceps and triceps brachii
      muscles. RESULTS: Compared with controls, patients with Parkinson's disease had
      higher stiffness in the muscle belly and tendon of the biceps brachii and in the
      tendon of the triceps brachii. In patients with Parkinson's disease, there was a
      positive correlation between muscle belly stiffness and parkinsonian rigidity in
      the biceps brachii. CONCLUSION: Patients with Parkinson's disease have higher
      passive stiffness of the muscle belly and tendon than healthy matched controls.

PMID- 21714010
TI  - High-frequency deep brain stimulation of the putamen improves bradykinesia in
      Parkinson's disease.
AB  - Deep brain stimulation is effective for a wide range of neurological disorders;
      however, its mechanisms of action remain unclear. With respect to Parkinson's
      disease, the existence of multiple effective targets suggests that putamen
      stimulation also may be effective and raises questions as to the mechanisms of
      action. Are there as many mechanisms of action as there are effective targets or
      some single or small set of mechanisms common to all effective targets? During
      the course of routine surgery of the globus pallidus interna in patients with
      Parkinson's disease, the deep brain stimulation lead was placed in the putamen en
      route to the globus pallidus interna. Recordings of hand opening and closing
      during high-frequency and no stimulation were made. Speed of the movements, based
      on the amplitude and frequency of the repetitive hand movements as well as the
      decay in amplitude, were studied. Hand speed in 6 subjects was statistically
      significantly faster during active deep brain stimulation than the no-stimulation
      condition. There were no statistically significant differences in decay in the
      amplitude of hand movements. High-frequency deep brain stimulation of the putamen
      improves bradykinesia in a hand-opening and -closing task in patients with
      Parkinson's disease. Consequently, high-frequency deep brain stimulation of
      virtually every structure in the basal ganglia-thalamic-cortical system improves
      bradykinesia. These observations, together with microelectrode recordings
      reported in the literature, argue that deep brain stimulation effects may be
      system specific and not structure specific.

PMID- 21714011
TI  - Feeding dystonia in McLeod syndrome.
AB  - BACKGROUND: The X-linked McLeod syndrome belongs to the group of
      neuroacanthocytosis syndromes and has a Huntington-disease-like phenotype with a
      choreatic movement disorder, cognitive alterations, and psychiatric symptoms.
      Another neuroacanthocytosis syndrome, the autosomal recessive chorea
      acanthocytosis, has a similar presentation, but distinct clinical features,
      believed to be characteristic, such as tongue protrusion dystonia, feeding
      dystonia, and rubber-man-like appearance. METHODS: This work comprised a case
      series of 3 patients with McLeod syndrome. RESULTS: The 3 patients with McLeod
      syndrome developed severe feeding dystonia and tongue protrusion as well as
      rubber-man-like appearance in 1 patient during the course of the disease.
      CONCLUSION: These observations indicate that there is an extended phenotypic
      overlap between McLeod syndrome and chorea-acanthocytosis.

PMID- 21714012
TI  - Full recovery of adult onset opsoclonus myoclonus syndrome after early
      immunotherapy: a case report.

PMID- 21714013
TI  - Probing the dynamics of CO2 and CH4 within the porous zirconium terephthalate UiO
      66(Zr): a synergic combination of neutron scattering measurements and molecular
      simulations.
AB  - Quasi-elastic neutron scattering (QENS) measurements combined with molecular
      dynamics (MD) simulations were conducted to deeply understand the concentration
      dependence of the self- and transport diffusivities of CH(4) and CO(2),
      respectively, in the humidity-resistant metal-organic framework UiO-66(Zr). The
      QENS measurements show that the self-diffusivity profile for CH(4) exhibits a
      maximum, while the transport diffusivity for CO(2) increases continuously at the
      loadings explored in this study. Our MD simulations can reproduce fairly well
      both the magnitude and the concentration dependence of each measured diffusivity.
      The flexibility of the framework implemented by deriving a new forcefield for UiO
      66(Zr) has a significant impact on the diffusivity of the two species. Methane
      diffuses faster than CO(2) over a broad range of loading, and this is in contrast
      to zeolites with narrow windows, for which opposite trends were observed. Further
      analysis of the MD trajectories indicates that the global microscopic diffusion
      mechanism involves a combination of intracage motions and jump sequences between
      tetrahedral and octahedral cages.

PMID- 21714014
TI  - The dilemma of CrIIINiII exchange interactions: ferromagnetism versus
      antiferromagnetism.
AB  - The sign of the exchange interaction in dinuclear Cr(III)Ni(II) complexes was
      analyzed using theoretical methods based on density functional theory. This
      approach allowed us to reproduce the experimental J values correctly. In
      addition, the Kahn-Briat model, which uses the square of the sum of the overlaps
      between the magnetic orbitals to correlate with the exchange coupling constant,
      provided a reasonable correlation between the different types of Cr(III)Ni(II)
      complexes when using biorthogonalized orbitals. We also examined the exchange
      interactions in two polynuclear Cr(III)Ni(II) complexes: a Cr(7)Ni ring and an S
      shaped Cr(12)Ni(3) complex. We concluded that both systems exhibit
      antiferromagentic interactions, and that the Cr(III)...Ni(II) interactions are
      similar in value to the C(III)...Cr(III) exchange couplings.

PMID- 21714015
TI  - Hybrid gold-nanoparticle-cored conjugated thiophene dendrimers: synthesis,
      characterization, and energy-transfer studies.
AB  - A series of hybrid Au-nanoparticle-dendrimer materials: nanoparticle-cored
      thiophene dendrimers (NCTDs) were synthesized, characterized, and investigated
      for their energy-transfer properties. These hybrid nanoparticles were obtained by
      the simultaneous and in situ reduction of gold(III) chloride and self-assembly of
      the thiol-containing thiophene dendritic ligands. The dendron ligands were
      radially attached to the gold nanoparticles and were analyzed by TEM, UV/Vis,
      (1)H NMR, and FTIR spectroscopies. The solution fluorescence of the attached
      thiophene dendrons are quenched progressively. Both alkyl-chain length and
      dendron size have significant influence on the energy-transfer efficiency, as
      well as on core sizes and size distribution of the Au nanoparticles. In spite of
      the phenomenon's dependence on nanoparticle size, the energy transfer generally
      follows the 1/d(2) distance dependence. Single NCTD nanoparticles were also
      adsorbed on highly ordered pyrolytic graphite (HOPG) and uniform aggregates were
      observed on mica flat substrates.

PMID- 21714016
TI  - Synthesis and photophysics of silicon phthalocyanine-perylenebisimide triads
      connected through rigid and flexible bridges.
AB  - Three new bisperylenebisimide-silicon phthalocyanine triads [(PBI)(2)-SiPcs 1, 2,
      and 3] connected with either rigid or flexible bridges were synthesized and
      characterized. A new synthetic approach to connect SiPc and PBI moieties through
      click chemistry produced triad 3 with an 80% yield. In (PBI)(2)-SiPc 1, PBI and
      SiPc are orthogonal and were connected with a rigid connector; triads 2 and 3
      bear flexible aliphatic bridges, resulting in a tilted (2) or nearly parallel
      arrangement (3) of PBI and SiPc. Photoinduced intramolecular processes in these
      (PBI)(2)-SiPcs were studied and the results are compared with those of the
      reference compounds SiPc-ref and PBI-ref. The occurrence of electron-transfer
      processes between the SiPc and PBI units was confirmed by time-resolved emission
      and transient absorption techniques. Charge-separated (CS) states with lifetimes
      of 0.91, 1.3 and 2.0 ns for triads 1, 2, and 3, respectively, were detected using
      femtosecond laser flash photolysis. Upon the addition of Mg(ClO(4))(2), an
      increase in the lifetime of the CS states to 59, 110 and 200 MUs was observed for
      triads (PBI)(2)-SiPcs 1, 2, and 3, respectively. The energy of the CS state
      (SiPc(.+)-PDI(.-)/Mg(2+)) is lower than the energy of both silicon phthalocyanine
      ((3)SiPc*-PDI) and perylenebisimide (SiPc-(3)PDI*) triplet excited states, which
      decelerates the metal ion-decoupled electron-transfer process for charge
      recombination to the ground state, thus increasing the lifetime of the CS state.
      The photophysics of the three triads demonstrate the importance of the rigidity
      of the spacer and the orientation between donor and acceptor units.

PMID- 21714017
TI  - Asymmetric catalysis with helical polymers.
AB  - Inspired by nature, the use of helical biopolymer catalysts has emerged over the
      last years as a new approach to asymmetric catalysis. In this Concept article the
      various approaches and designs and their application in asymmetric catalysis will
      be discussed.

PMID- 21714018
TI  - A new phosphine oxide host based on ortho-disubstituted dibenzofuran for
      efficient electrophosphorescence: towards high triplet state excited levels and
      excellent thermal, morphological and efficiency stability.
AB  - An efficient host for blue and green electrophosphorescence, 4,6
      bis(diphenylphosphoryl)dibenzofuran (o-DBFDPO), with the structure of a short
      axis-substituted dibenzofuran was designed and synthesised. It appears that the
      greater density of the diphenylphosphine oxide (DPPO) moieties in the short-axis
      substitution configuration effectively restrains the intermolecular interactions,
      because only very weak pi-pi stacking interactions could be observed, with a
      centroid-to-centroid distance of 3.960 A. The improved thermal stability of o
      DBFDPO was corroborated by its very high glass transition temperature (T(g)) of
      191  degrees C, which is the result of the symmetric disubstitution structure.
      Photophysical investigation showed o-DBFDPO to be superior to the monosubstituted
      derivative, with a longer lifetime (1.95 ns) and a higher photoluminescent
      quantum efficiency (61 %). The lower first singlet state excited level (3.63 eV)
      of o-DBFDPO demonstrates the stronger polarisation effect attributable to the
      greater number of DPPO moieties. Simultaneously, an extremely high first triplet
      state excited level (T(1)) of 3.16 eV is observed, demonstrating the tiny
      influence of short-axis substitution on T(1). The improved carrier injection
      ability, which contributed to low driving voltages of blue- and green-emitting
      phosphorescent organic light-emitting diodes (PHOLEDs), was further confirmed by
      Gaussian calculation. Furthermore, the better thermal and morphological
      properties of o-DBFDPO and the matched frontier molecular orbital (FMO) levels in
      the devices significantly reduced efficiency roll-offs. Efficient blue and green
      electrophosphorescence based on the o-DBFDPO host was demonstrated.

PMID- 21714019
TI  - Facile synthesis of wide-bandgap fluorinated graphene semiconductors.
AB  - The bandgap opening of graphene is extremely important for the expansion of the
      applications of graphene-based materials into optoelectronics and photonics.
      Current methods to open the bandgap of graphene have intrinsic drawbacks
      including small bandgap openings, the use hazardous/harsh chemical oxidations,
      and the requirement of expensive chemical-vapor deposition technologies. Herein,
      an eco-friendly, highly effective, low-cost, and highly scalable synthetic
      approach is reported for synthesizing wide-bandgap fluorinated graphene (F
      graphene or or fluorographene) semiconductors under ambient conditions. In this
      synthesis, ionic liquids are used as the only chemical to exfoliate commercially
      available fluorinated graphite into single and few-layer F-graphene. Experimental
      and theoretical results show that the bandgap of F-graphene is largely dependent
      on the F coverage and configuration, and thereby can be tuned over a very wide
      range.

PMID- 21714020
TI  - On the nature of actinide- and lanthanide-metal bonds in heterobimetallic
      compounds.
AB  - Eleven experimentally characterized complexes containing heterobimetallic bonds
      between elements of the f-block and other elements were examined by quantum
      chemical methods: [(eta(5)-C(5)H(5))(2)(THF)LuRu(eta(5)-C(5)H(5))(CO)(2)],
      [(eta(5)-C(5)Me(5))(2)(I)ThRu(eta(5)-C(5)H(5))(CO)(2)], [(eta(5)
      C(5)H(5))(2)YRe(eta(5)-C(5)H(5))(2)], [{N(CH(2)CH(2)NSiMe(3))(3)}URe(eta(5)
      C(5)H(5))(2)], [Y{Ga(NArCh)(2)}{C(PPh(2)NSiH(3))(2)}(CH(3)OCH(3))(2)],
      [{N(CH(2)CH(2)NSiMe(3))(3)}U{Ga(NArCH)(2)}(THF)], [(eta(5)-C(5)H(5))(3)UGa(eta(5)
      C(5)Me(5))], [Yb(eta(5)-C(5)H(5)){Si(SiMe(3))(3)(THF)(2)}], [(eta(5)
      C(5)H(5))(3)U(SnPh(3))], [(eta(5)-C(5)H(5))(3)U(SiPh(3))], and
      (Ph[Me]N)(3)USi(SiMe(3))(3). Geometries in good agreement with experiment were
      obtained at the density functional level of theory. The multiconfigurational
      complete active space self-consistent field method (CASSCF) and subsequent
      corrections with second order perturbation theory (CASPT2) were applied to
      further understand the electronic structure of the lanthanide/actinide-metal (or
      metal-metalloid) bonds. Fragment calculations and energy-decomposition analyses
      were also performed and indicate that charge transfer occurs from one supported
      metal fragment to the other, while the bonding itself is always dominated by
      ionic character.

PMID- 21714021
TI  - Segmental dynamics of PEO/LiClO4 complex crystals and their influence on the Li+
      ion transportation in crystal lattices: A 13C solid-state NMR approach.
AB  - The structure and chain dynamics of polyethylene oxide (PEO)/LiClO(4) complex
      crystals were studied by employing state-of-the-art solid-state (13)C NMR
      techniques. Remarkable helical jump motions of the PEO segments in the complex
      crystals at ambient temperatures were clearly demonstrated. The jump motions are
      believed to induce the transportation of the coordinated Li(+) ions along the
      crystallographic c axis, providing a novel mechanism of ionic conductivity of the
      complex crystals. In addition, this work also shows that solid-state high
      resolution (13)C NMR spectroscopy can be a powerful and general tool for
      elucidating phase structures, dynamics, and subsequently the conduction mechanism
      of crystalline polymer electrolytes.

PMID- 21714022
TI  - pKa values of chiral Bronsted acid catalysts: phosphoric acids/amides,
      sulfonyl/sulfuryl imides, and perfluorinated TADDOLs (TEFDDOLs).

PMID- 21714023
TI  - Luminescent rhenium(I) polypyridine complexes appended with an alpha-D-glucose
      moiety as novel biomolecular and cellular probes.

PMID- 21714024
TI  - Crystal structure of the C17/25 subcomplex from Schizosaccharomyces pombe RNA
      polymerase III.
AB  - Eukaryotic RNA polymerase III (Pol III) is a multisubunit enzyme responsible for
      transcribing tRNA, 5S rRNA, and several small RNAs. Of the 17 subunits in Pol
      III, the C17 (Rpc17) and C25 (Rpc25) subunits form a stable subcomplex that
      protrudes from the core polymerase. In this study, we determined the crystal
      structure of the C17/25 subcomplex from Schizosaccharomyces pombe. The subcomplex
      adopts an elongated shape, and each subunit has two domains. The two subunits in
      the subcomplex are tightly packed and extensively interact, with a contact area
      of 2080 A(2) . The overall conformation of S. pombe C17/25 is considerably
      different from the previously reported structure of C17/25 from Saccharomyces
      cerevisiae, with respect to the position of the C17 HRDC domain, a helix bundle
      essential for cell viability. In contrast, the S. pombe C17/25 structure is quite
      similar to those of the Pol II and archaeal counterparts, Rpb4/7 and RpoE/F,
      respectively, despite the low sequence similarity. A phylogenetic comparison of
      the C17 subunits among eukaryotes revealed that they can be classified into three
      groups, according to the length of the interdomain linker. S. pombe C17, as well
      as Rpb4 and RpoF, belongs to the largest group, with the short linker. On the
      other hand, S. cerevisiae C17 belongs to the smallest group, with the long
      linker, which probably enables the subcomplex to assume the alternative
      conformation.

PMID- 21714025
TI  - Green fluorescent protein: a perspective.
AB  - A brief personal perspective is provided for green fluorescent protein (GFP),
      covering the period 1994-2011. The topics discussed are primarily those in which
      my research group has made a contribution and include structure and function of
      the GFP polypeptide, the mechanism of fluorescence emission, excited state
      protein transfer, the design of ratiometric fluorescent protein biosensors and an
      overview of the fluorescent proteins derived from coral reef animals. Structure
      function relationships in photoswitchable fluorescent proteins and nonfluorescent
      chromoproteins are also briefly covered.

PMID- 21714026
TI  - A matching algorithm for catalytic residue site selection in computational enzyme
      design.
AB  - A loop closure-based sequential algorithm, PRODA_MATCH, was developed to match
      catalytic residues onto a scaffold for enzyme design in silico. The computational
      complexity of this algorithm is polynomial with respect to the number of active
      sites, the number of catalytic residues, and the maximal iteration number of
      cyclic coordinate descent steps. This matching algorithm is independent of a
      rotamer library that enables the catalytic residue to take any required
      conformation during the reaction coordinate. The catalytic geometric parameters
      defined between functional groups of transition state (TS) and the catalytic
      residues are continuously optimized to identify the accurate position of the TS.
      Pseudo-spheres are introduced for surrounding residues, which make the algorithm
      take binding into account as early as during the matching process. Recapitulation
      of native catalytic residue sites was used as a benchmark to evaluate the novel
      algorithm. The calculation results for the test set show that the native
      catalytic residue sites were successfully identified and ranked within the top 10
      designs for 7 of the 10 chemical reactions. This indicates that the matching
      algorithm has the potential to be used for designing industrial enzymes for
      desired reactions.

PMID- 21714027
TI  - Poly(cyclic imino ether)s beyond 2-substituted-2-oxazolines.
AB  - 2-Oxazolines (2-OZO) are 5-membered cyclic imino ethers whose cationic ring
      opening polymerization (CROP) mechanism and resulting polymer properties are
      extensively studied. However, also 6- and 7-membered cyclic imino ethers can be
      polymerized via CROP. Together with the much less studied 4- and 5-substituted
      main-chain chiral poly(2-oxazoline)s (P-2-OZO), these compounds are interesting
      monomers to enhance the versatility of (co)poly(cyclic imino ether)s. To
      emphasize the potential of such alternative cyclic imino ether monomers, we
      provide an overview on the polymerizations of 2-oxazine (2-OZI) and chiral 4- and
      5-substituted 2-OZO as well as of selected properties of the resulting polymers.
      In addition, the hydrolysis of these polymers into the corresponding
      poly(alkylene imine)s will be addressed.

PMID- 21714028
TI  - Epitaxial growth of crystalline polyaniline on reduced graphene oxide.
AB  - Due to its unique electronic properties, graphene has already been identified as
      a promising material for future carbon based electronics. To develop graphene
      technology, the fabrication of a high quality P-N junction is a great challenge.
      Here, we describe a general technique to grow single crystalline polyaniline
      (PANI) films on graphene sheets using in situ polymerization via the oxidation
      reduction of aniline monomer and graphene oxide, respectively, to fabricate a
      high quality P-N junction, which shows diode-like behavior with a remarkably low
      turn-on voltage (60 mV) and high rectification ratio (1880:1) up to a voltage of
      0.2 V. The origin of these superior electronic properties is the preferential
      growth of a highly crystalline PANI film as well as lattice matching between the
      d-values [~2.48 A] of graphene and {120} planes of PANI.

PMID- 21714029
TI  - A primer on meiotic resumption in starfish oocytes: the proposed signaling
      pathway triggered by maturation-inducing hormone.
AB  - This short review updates the maturation-inducing hormonal signaling in starfish
      oocytes. In this system, the activation of cyclin B-Cdc2 kinase (Cdk1) that leads
      to meiotic resumption does not require new protein synthesis. The key
      intracellular mediator after hormonal stimulation by 1-methyladenine is the
      protein kinase Akt/PKB, which in turn directly downregulates Myt1 and upregulates
      Cdc25 toward the activation of cyclin B-Cdc2. Mitotic kinases including Aurora,
      Plk1 and Greatwall are activated downstream of cyclin B-Cdc2. The starfish oocyte
      thus provides a simple model system for the study of meiotic resumption.

PMID- 21714031
TI  - Marked limb bilateral asymmetry in an agricultural endogamous population of North
      India.
AB  - OBJECTIVES: The purpose of this study is to evaluate directional asymmetry in the
      most commonly measured dimensions of limbs in adult male Gujjars of North India.
      METHODS: The sample for this study is based on 967 adult male Gujjars ranging in
      age from 18 to 30 years settled in subHimalayan region in the foothills of
      Siwaliks surrounding Chandigarh city in North India. The data comprise nineteen
      anthropometric measurements taken on left and right side of each subject. Gujjars
      are one of the major caste groups of India having agriculture as the main
      occupation. This group is also homogeneous in terms of ethnic composition,
      language, and religious affiliation. Using appropriate statistical methods, the
      bilateral asymmetry was evaluated in the human body. RESULTS: The results
      indicate that significant bilateral asymmetry exists in some of the limb
      dimensions. Upper extremity dimensions are more asymmetric than that of lower
      extremity dimensions. Most of the arm dimensions are significantly larger on the
      right side except hand length and triceps skinfold in younger sample and triceps
      skinfold in older sample, which are significantly larger on the left side. Most
      of the upper extremity dimensions are larger on the right side, however; most of
      the lower extremity dimensions are larger on the left side. CONCLUSIONS: Marked
      directional asymmetry exists in 13 measurements out of a total 18 taken for the
      study. This significant right-sided asymmetry may be attributed to the fact that
      individuals have normal tendency to favor the right side for power activities
      involving upper limbs, i.e., throwing for distance, sports activities, and in
      this investigation, working with agricultural tools like Khurpa, Datti, Kassi
      (Indian agricultural tools) for long durations. More frequent use of the
      preferred side results in heavier or stronger muscles of that side and
      consequently heavier and stronger bones.

PMID- 21714032
TI  - Drug safety issues of nimesulide in China--nimesulide-induced liver injury.

PMID- 21714033
TI  - Re: How can we produce relevant information for decision makers from small area
      variation studies?

PMID- 21714035
TI  - Managing security and privacy concerns over data storage in healthcare research.
AB  - PURPOSE: Issues surrounding data security and privacy are of great importance
      when handling sensitive health-related data for research. The emphasis in the
      past has been on balancing the risks to individuals with the benefit to society
      of the use of databases for research. However, a new way of looking at such
      issues is that by optimising procedures and policies regarding security and
      privacy of data to the extent that there is no appreciable risk to the privacy of
      individuals, we can create a 'win-win' situation in which everyone benefits, and
      pharmacoepidemiological research can flourish with public support. We discuss
      holistic measures, involving both information technology and people, taken to
      improve the security and privacy of data storage. METHODS: After an internal
      review, we commissioned an external audit by an independent consultant with a
      view to optimising our data storage and handling procedures. RESULTS:
      Improvements to our policies and procedures were implemented as a result of the
      audit. CONCLUSIONS: By optimising our storage of data, we hope to inspire public
      confidence and hence cooperation with the use of health care data in research.

PMID- 21714036
TI  - Cerebral hemodynamics in newborn infants exposed to speech sounds: a whole-head
      optical topography study.
AB  - Considerable knowledge on neural development related to speech perception has
      been obtained by functional imaging studies using near-infrared spectroscopy
      (optical topography). In particular, a pioneering study showed stronger left
      dominant activation in the temporal lobe for (normal) forward speech (FW) than
      for (reversed) backward speech (BW) in neonates. However, it is unclear whether
      this stronger left-dominant activation for FW is equally observed for any
      language or is clearer for the mother tongue. We hypothesized that the maternal
      language elicits clearer activation than a foreign language in newborns because
      of their prenatal and/or few-day postnatal exposure to the maternal language. To
      test this hypothesis, we developed a whole-head optode cap for 72-channel optical
      topography and visualized the spatiotemporal hemodynamics in the brains of 17
      Japanese newborns when they were exposed to FW and BW in their maternal language
      (Japanese) and in a foreign language (English). Statistical analysis showed that
      all sound stimuli together induced significant activation in the bilateral
      temporal regions and the frontal region. They also showed that the left temporal
      parietal region was significantly more active for Japanese FW than Japanese BW or
      English FW, while no significant difference between FW and BW was shown for
      English. This supports our hypothesis and suggests that the few-day-old brain
      begins to become attuned to the maternal language. Together with a finding of
      equivalent activation for all sound stimuli in the adjacent measurement positions
      in the temporal region, these findings further clarify the functional
      organization of the neonatal brain.

PMID- 21714037
TI  - Brief report: benchmarking human pluripotent stem cell markers during
      differentiation into the three germ layers unveils a striking heterogeneity: all
      markers are not equal.
AB  - Pluripotent stem cells (PSC) are functionally characterized by their capacity to
      differentiate into all the cell types from the three germ layers. A wide range of
      markers, the expression of which is associated with pluripotency, has been used
      as surrogate evidence of PSC pluripotency, but their respective relevance is
      poorly documented. Here, we compared by polychromatic flow cytometry the kinetics
      of loss of expression of eight widely used pluripotency markers (SSEA3, SSEA4,
      TRA-1-60, TRA-1-81, CD24, OCT4, NANOG, and alkaline phosphatase [AP]) at days 0,
      5, 7, and 9 after induction of PSC differentiation into cells representative of
      the three germ layers. Strikingly, each marker showed a different and specific
      kinetics of disappearance that was similar in all the PSC lines used and for all
      the induced differentiation pathways. OCT4, SSEA3, and TRA-1-60 were repeatedly
      the first markers to be downregulated, and their expression was completely lost
      at day 9. By contrast, AP activity, CD24, and NANOG proteins were still
      detectable at day 9. In addition, we show that differentiation markers are
      coexpressed with pluripotency markers before the latter begin to disappear. These
      results suggest that OCT4, SSEA3, and TRA-1-60 might be better to trace in vitro
      the emergence of pluripotent cells during reprogramming.

PMID- 21714038
TI  - Expression of Tlx in both stem cells and transit amplifying progenitors regulates
      stem cell activation and differentiation in the neonatal lateral subependymal
      zone.
AB  - Niche homeostasis in the postnatal subependymal zone of the lateral ventricle
      (lSEZ) requires coordinated proliferation and differentiation of neural
      progenitor cells. The mechanisms regulating this balance are scarcely known.
      Recent observations indicate that the orphan nuclear receptor Tlx is an intrinsic
      factor essential in maintaining this balance. However, the effect of Tlx on gene
      expression depends on age and cell-type cues. Therefore, it is essential to
      establish its expression pattern at different developmental ages. Here, we show
      for the first time that in the neonatal lSEZ activated neural stem cells (NSCs)
      and especially transit-amplifying progenitors (TAPs) express Tlx and that its
      expression may be regulated at the posttranscriptional level. We also provide
      evidence that in both cell types Tlx affects gene expression in a positive and
      negative manner. In activated NSCs, but not in TAPs, absence of Tlx leads to
      overexpression of negative cell cycle regulators and impairment of proliferation.
      Moreover, in both cell types, the homeobox transcription factor Dlx2 is
      downregulated in the absence of Tlx. This is paralleled by increased expression
      of Olig2 in activated NSCs and glial fibrillary acidic protein in TAPs,
      indicating that in both populations Tlx decreases gliogenesis. Consistent with
      this, we found a higher proportion of cells expressing glial makers in the
      neonatal lSEZ of mutant mice than in the wild type counterpart. Thus, Tlx playing
      a dual role affects the expression of distinct genes in these two lSEZ cell
      types.

PMID- 21714039
TI  - First do no harm: iatrogenic maintaining factors in anorexia nervosa.
AB  - The aim of this paper is to reflect on the way that we as clinicians may play an
      inadvertent role in perpetuating eating disordered behaviour. This is considered
      within the theoretical framework of Schmidt and Treasures' maintenance model of
      anorexia nervosa (AN). The model includes four main domains; interpersonal
      factors, pro-AN beliefs, emotional style and thinking style. Interpersonal
      reactions are of particular relevance as clinicians (as with family members) may
      react with high expressed emotion and unknowingly encourage eating disorder
      behaviours to continue. Hostility in the form of coercive refeeding in either a
      hospital or outpatient setting may strengthen conditioned food avoidance and
      pessimism may hamper motivation to change. Negative schema common to eating
      disorders, for example low self-esteem, perfectionism and striving for social
      value may augment existing or initiate new eating disorder behaviour. Services
      can become a reinforcing influence by providing an overly protective, palliating
      environment which ensures safety, security and acceptance whilst reducing
      loneliness and isolation. This stifles the need for an individual to develop
      their own sense of responsibility, autonomy and independence allowing avoidance
      to dominate. Furthermore, the highly structured environment of inpatient care
      supports the rigid attention to detail and inflexibility that is characteristic
      of people with eating disorders, and allows these negative behaviours to thrive.
      Careful planning of service provision, reflective practice, supervision and
      regular team feedback is essential to prevent iatrogenic harm.

PMID- 21714040
TI  - Convergent validity of the eating disorder examination and the eating disorder
      examination-questionnaire among university women in Norway.
AB  - The present study compared the Eating Disorder Examination (EDE; 16.0) and the
      Eating Disorder Examination-Questionnaire (EDE-Q; 6.0) and investigated the
      psychometric properties of the Norwegian translation of the EDE. Fifty-eight
      university women aged 19-41 years (mean BMI = 23) were assessed with the EDE and
      EDE-Q. Satisfactory internal consistency and inter-rater reliability were
      demonstrated for the Norwegian translation of the EDE. Generally high convergent
      validity between the EDE and EDE-Q was found, with correlations ranging from 0.60
      (Eating Concern) to 0.86 (Weight Concern). Agreement for OBEs and vomiting were
      excellent, while driven exercising generated lower levels of convergence.
      Consistent with prior studies, the EDE-Q generated significantly higher levels of
      psychopathology, although effect sizes were small. Owing to the significantly
      higher EDE-Q scores, it is ill advised to administer these two instruments
      interchangeably, as this may fail to produce meaningful data.

PMID- 21714044
TI  - The mechanism of potassium promoter: enhancing the stability of active surfaces.

PMID- 21714045
TI  - Nanosizing intermetallic compounds onto carbon nanotubes: active and selective
      hydrogenation catalysts.

PMID- 21714046
TI  - Construction and potential applications of a functionalized cell with an
      intracellular mineral scaffold.

PMID- 21714047
TI  - Distinct reactivity differences of metal oxo and its corresponding hydroxo
      moieties in oxidations: implications from a manganese(IV) complex having
      dihydroxide ligand.

PMID- 21714048
TI  - Ordered gelation of chemically converted graphene for next-generation
      electroconductive hydrogel films.

PMID- 21714049
TI  - Facile preparation of multifunctional upconversion nanoprobes for multimodal
      imaging and dual-targeted photothermal therapy.

PMID- 21714050
TI  - Stereoselective synthesis of highly substituted enamides by an oxidative Heck
      reaction.

PMID- 21714051
TI  - Genetically programmed in vivo packaging of protein cargo and its controlled
      release from bacteriophage P22.

PMID- 21714052
TI  - N-heterocyclic carbenes: organocatalysts with moderate nucleophilicity but
      extraordinarily high Lewis basicity.

PMID- 21714053
TI  - Highly enantioselective alpha alkylation of aldehydes with 1,3-benzodithiolylium
      tetrafluoroborate: a formal organocatalytic alpha alkylation of aldehydes by the
      carbenium ion.

PMID- 21714056
TI  - Iminodipropionic acid as the leaving group for DNA polymerization by HIV-1
      reverse transcriptase.
AB  - Previous studies have demonstrated that some selected amino monoacids and amino
      diacids can function as leaving groups in the polymerase-catalyzed incorporation
      of deoxynucleotides into DNA. Among these, the iminodiacetic acid phosphoramidate
      of deoxyadenosine monophosphate (IDA-dAMP) represents an interesting example, as
      it could overcome some of the problems observed when using L-aspartic acid as the
      leaving group, that is, poor chain elongation. We have now synthesized and
      evaluated a series of IDA-dAMP analogues that bear either an extended aliphatic
      chain in the amino acid function, or a phosphonic acid moiety (substituting for
      the carboxylic acid function). Among these compounds, the nucleotide with an
      iminodipropionic acid leaving group (IDP-dAMP) was identified as the best
      substrate; the excellent single incorporation (91 % conversion to a P+1 strand at
      50 MUM) was at a substrate concentration ten times lower than that used for IDA
      dAMP). This nucleotide also presented improved kinetics and elongation capability
      compared to IDA-dAMP. The analogues with T, G, and C base moieties were also
      investigated for their incorporation ability with HIV-1 RT. The incorporation
      efficiency was found to decrease in the order A>T>G>C. The properties of the
      iminodipropionic acid as the leaving group surpass those of previously evaluated
      leaving groups; this acid will be a prime candidate for in vivo testing.

PMID- 21714057
TI  - Discovery of a metagenome-derived enzyme that produces branched-chain acyl-(acyl
      carrier-protein)s from branched-chain alpha-keto acids.

PMID- 21714058
TI  - Toxicities and sublethal effects of seven neonicotinoid insecticides on survival,
      growth and reproduction of imidacloprid-resistant cotton aphid, Aphis gossypii.
AB  - BACKGROUND: Imidacloprid has been a major neonicotinoid insecticide for
      controlling Aphis gossypii (Glover) (Homoptera: Aphididae) and other piercing
      sucking pests. However, the resistance to imidacloprid has been recorded in many
      target insects. At the same time, cross-resistance of imidacloprid and other
      insecticides, especially neonicotinoid insecticides, has been detected. RESULTS:
      Results showed that the level of cross-resistance was different between
      imidacloprid and tested neonicotinoid insecticides (no cross-resistance:
      dinotefuran, thiamethoxam and clothianidin; a 3.68-5.79-fold cross-resistance:
      acetamiprid, nitenpyram and thiacloprid). In the study of sublethal effects,
      imidacloprid at LC(20) doses could suppress weight gain and honeydew excretion,
      but showed no significant effects on longevity and fecundity of the imidacloprid
      resistant cotton aphid, A. gossypii. However, other neonicotinoid insecticides
      showed significant adverse effects on biological characteristics (body weight,
      honeydew excretion, longevity and fecundity) in the order of dinotefuran >
      thiamethoxam and clothianidin > nitenpyram > thiacloprid and acetamiprid.
      CONCLUSION: The results indicated that dinotefuran is the most effective
      insecticide for use against imidacloprid-resistant A. gossypii. To avoid further
      resistance development, the use of nitenpyram, acetamiprid and thiacloprid should
      be avoided on imidacloprid-resistant populations of A. gossypii.

PMID- 21714059
TI  - Baseline susceptibilities of B- and Q-biotype Bemisia tabaci to anthranilic
      diamides in Arizona.
AB  - BACKGROUND: Development of pyriproxyfen and neonicotinoid resistance in the B
      biotype whitefly and recent introduction of the Q biotype have the potential to
      threaten current whitefly management programs in Arizona. The possibility of
      integrating the novel anthranilic diamides chlorantraniliprole and
      cyantraniliprole into the current program to tackle these threats largely depends
      on whether these compounds have cross-resistance with pyriproxyfen and
      neonicotinoids in whiteflies. To address this question, the authors bioassayed a
      susceptible B-biotype strain, a pyriproxyfen-resistant B-biotype strain, four
      multiply resistant Q-biotype strains and 16 B-biotype field populations from
      Arizona with a systemic uptake bioassay developed in the present study. RESULTS:
      The magnitude of variations in LC(50) and LC(99) among the B-biotype populations
      or the Q-biotype strains was less than fivefold and tenfold, respectively, for
      both chlorantraniliprole and cyantraniliprole. The Q-biotype strains were
      relatively more tolerant than the B-biotype populations. No correlations were
      observed between the LC(50) (or LC(99)) values of the two diamides against the B-
      and Q-biotype populations tested and their survival rates at a discriminating
      dose of pyriproxyfen or imidacloprid. CONCLUSION: These results indicate the
      absence of cross-resistance between the two anthranilic diamides and the
      currently used neonicotinoids and pyriproxyfen. Future variation in
      susceptibility of field populations to chlorantraniliprole and cyantraniliprole
      could be documented according to the baseline susceptibility range of the
      populations tested in this study.

PMID- 21714060
TI  - Droplet size and efficacy of an adulticide-larvicide ultralow-volume formulation
      on Aedes aegypti using different solvents and spray application methods.
AB  - BACKGROUND: When cases of dengue are reported or the density of adult Aedes
      aegypti (L.) becomes too high, ultralow-volume (ULV) application of insecticides
      is the recommended control method. The droplet size of an aerosol insecticide
      influences its efficiency in killing adult mosquitoes. Many studies have been
      carried out to determine the optimum droplet size that maximises vector control
      efforts, but only a few have determined droplet-size spectra for specific
      equipment using different solvents and comparing thermal and non-thermal
      aerosols. RESULTS: The present study showed that the droplet size for a water
      based adulticide-larvicide formulation was larger than for the same formulation
      diluted in gasoil or biodiesel. No significant differences in adult mortality
      were observed between sprayers and solvents, but efficacy decreased with distance
      from the sprayer nozzle. Adult emergence inhibition was more than 90% when using
      water as a solvent for both thermal and cold foggers, and the efficacy did not
      decrease with distance from the sprayer nozzle. On the other hand, oil-based
      solvents became less effective with distance. CONCLUSION: The use of water as a
      solvent with both thermal and cold foggers improves the efficacy of the studied
      formulation containing permethrin as adulticide and pyriproxyfen as larvicide in
      scaled-up assays. Moreover, it reduces the environmental impact and costs of
      spraying by comparison with formulations using oil solvents.

PMID- 21714061
TI  - Zebrafish Tshz3b negatively regulates Hox function in the developing hindbrain.
AB  - In flies, the zinc-finger protein Teashirt promotes trunk segmental identities,
      in part, by repressing the expression and function of anterior hox paralog group
      (PG) 1-4 genes that specify head fates. Anterior-posterior patterning of the
      vertebrate hindbrain also requires Hox PG 1-4 function, but the role of
      vertebrate teashirt-related genes in this process has not been investigated. In
      this work, we use overexpression and structure-function analyses to show that
      zebrafish tshz3b antagonizes Hox-dependent hindbrain segmentation. Ectopic Tshz3b
      perturbs the specification of rhombomere identities and leads to the caudal
      expansion of r1, the only rhombomere whose identity is specified independently of
      Hox function. This overexpression phenotype does not require the homeodomain and
      C-terminal zinc fingers that are unique to vertebrate Teashirt-related proteins,
      but does require that Tshz3b function as a repressor. Together, these results
      argue that the negative regulation of Hox PG 1-4 function is a conserved
      characteristic of Teashirt-related proteins.

PMID- 21714062
TI  - A case-controlled study of the safety and efficacy of transjugular intrahepatic
      portosystemic shunts after liver transplantation.
AB  - The role of transjugular intrahepatic portosystemic shunt (TIPS) insertion in
      managing the complications of portal hypertension is well established, but its
      utility in patients who have previously undergone liver transplantation is not
      well documented. Twenty-two orthotopic liver transplantation (OLT) patients and
      44 nontransplant patients (matched controls) who underwent TIPS were analyzed. In
      the OLT patients, the TIPS procedure was performed at a median of 44.8 months
      (range = 0.3-143 months) after transplantation. Eight (36.4%) had variceal
      bleeding, and 14 (63.6%) had refractory ascites. The underlying liver disease was
      cholestatic in 10 (45.4%) and viral in 4 (18.2%). The mean pre-TIPS Model for End
      Stage Liver Disease (MELD) score was 13.4 +/- 5.1. There were no significant
      differences in age, sex, indication, etiology, or MELD score with respect to the
      control group. The mean initial portal pressure gradients (PPGs) were similar in
      the 2 groups (21.0 versus 22.4 mm Hg for the OLT patients and controls,
      respectively), but the final PPG was lower in the control group (9.9 versus 6.9
      mm Hg, P < 0.05). The rates of both technical success and clinical success were
      higher in the control group versus the OLT group [95.5% versus 68.2% (P < 0.05)
      and 93.2% versus 77.2% (P < 0.05), respectively]. The rates of complications and
      post-TIPS encephalopathy were similar in the 2 groups, and there was a trend
      toward increased rates of shunt insufficiency in the OLT group. The mortality
      rate of the patients with a pre-TIPS MELD score > 15 was significantly higher in
      the OLT group [hazard ratio (HR) = 4.32, 95% confidence interval (CI) = 1.45
      12.88, P < 0.05], but the mortality rates of the patients with a pre-TIPS MELD
      score < 15 were similar in the 2 groups. In the OLT group, the predictors of
      increased mortality were the pre-TIPS MELD score (HR = 1.161, 95% CI = 1.036
      1.305, P < 0.05) and pre-TIPS MELD scores > 15 (HR = 5.846, 95% CI = 1.754
      19.485, P < 0.05). In conclusion, TIPS insertion is feasible in transplant
      recipients, although its efficacy is lower in these patients versus control
      patients. Outcomes are poor for OLT recipients with a pre-TIPS MELD score > 15.

PMID- 21714063
TI  - Need for the clarification of data in a recent meta-analysis about cytokine gene
      polymorphisms and acute liver graft rejection.

PMID- 21714064
TI  - It is time to look inward.

PMID- 21714065
TI  - What is the role of adjuvant therapy after liver transplantation for
      hepatocellular carcinoma?

PMID- 21714066
TI  - Markers for microvascular invasion in hepatocellular carcinoma: where do we
      stand?

PMID- 21714067
TI  - Association between polymorphisms of DRD2 and DRD4 and opioid dependence:
      evidence from the current studies.
AB  - Several studies have assessed the association between genetic polymorphisms of
      DRD2 and DRD4 genes and opioid dependence risk, while the results were
      inconsistent. We performed a meta-analysis, including 6,846 opioid dependence
      cases and 4,187 controls from 22 individual studies, to evaluate the roles of
      four variants (DRD2 -141ins/delC, rs1799732; DRD2 311 Ser > Cys, rs1801028; DRD2
      related TaqI A, rs1800497 and DRD4 exon III VNTR) in opioid dependence for the
      first time. We found that the -141delC polymorphism was significantly associated
      with increased risk of opioid dependence (homozygote comparison: odds ratios
      [OR], 2.71; 95% confidence interval [CI], 1.74-4.22; dominant comparison: OR,
      1.27; 95% CI, 1.09-1.48). Similarly, the TaqI A1 polymorphism was also
      significantly increased opioid dependence risk (homozygote comparison: OR, 2.06;
      95% CI, 1.25-3.42; dominant comparison: OR, 1.34; 95% CI, 1.08-1.67). Moreover,
      long allele (>=5-repeat) and 7-repeat allele of DRD4 exon III VNTR were found to
      be associated with significantly increased opioid dependence risk (OR, 1.50; 95%
      CI, 1.24-1.80 and OR, 1.57; 95%, 1.18-2.09, respectively). However, no
      association was detected between the DRD2 311 Ser > Cys polymorphism and opioid
      dependence. In conclusion, our results suggested that DRD2 -141ins/delC, DRD2
      related TaqI A and DRD4 exon III VNTR polymorphisms might play important roles in
      the development of opioid dependence.

PMID- 21714068
TI  - Founder's award to Antonios G. Mikos, Ph.D., 2011 Society for Biomaterials annual
      meeting and exposition, Orlando, Florida, April 13-16, 2011: Bones to
      biomaterials and back again--20 years of taking cues from nature to engineer
      synthetic polymer scaffolds.
AB  - For biomaterials scientists focusing on tissue engineering applications, the gold
      standard material is healthy, autologous tissue. Ideal material properties and
      construct design parameters are thus both obvious and often times unachievable;
      additional considerations such as construct delivery and the underlying pathology
      necessitating new tissue yield additional design challenges with solutions that
      are not evident in nature. For the past nearly two decades, our laboratory and
      collaborators have aimed to develop both new biomaterials and a better
      understanding of the complex interplay between material and host tissue to
      facilitate bone and cartilage regeneration. Various approaches have ranged from
      mimicking native tissue material properties and architecture to developing
      systems for bioactive molecule delivery as soluble factors or bound directly to
      the biomaterial substrate. Such technologies have allowed others and us to design
      synthetic biomaterials incorporating increasing levels of complexity found in
      native tissues with promising advances made toward translational success. Recent
      work focuses on translation of these technologies in specific clinical situations
      through the use of adjunctive biomaterials designed to address existing
      pathologies or guide host-material integration.

PMID- 21714069
TI  - Sleep quality and diurnal preference in a sample of young adults: associations
      with 5HTTLPR, PER3, and CLOCK 3111.
AB  - Research investigating associations between specific genes and individual
      differences with regards to the quality and timing of sleep has primarily
      focussed on serotonin-related and clock genes. However, there are only a few
      studies of this type and most of those to date have not considered the
      possibility of gene-environment interaction. Here, we describe associations
      between sleep quality and diurnal preference and three functional polymorphisms:
      5HTTLPR, PERIOD3, and CLOCK 3111. Furthermore, we assessed whether associations
      between genotypes and sleep phenotypes were moderated by negative life events-a
      test of gene-environment interaction. DNA from buccal swabs was collected from
      947 individuals [mean age = 20.3 years (SD = 1.77), age range = 18-27 years;
      61.8% female] and genotyped for the three polymorphisms. Participants completed
      the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire.
      There was a significant main effect of 5HTTLPR on sleep quality, indicating that
      "long-long" homozygotes experienced significantly poorer sleep quality (mean =
      6.35, SD = 3.36) than carriers of at least one "short" allele (mean = 5.67, SD =
      2.96; beta = -0.34, P = 0.005). There were no main effects of 5HTTLPR on diurnal
      preference; no main effects of PERIOD3 or CLOCK on sleep quality or diurnal
      preference; and no significant interactions with negative life events. The main
      effect of the "long" 5HTTLPR allele contradicts previous research, suggesting
      that perhaps the effects of this gene are heterogeneous in different populations.
      Failure to replicate previous research in relation to PERIOD3 and CLOCK concurs
      with previous research suggesting that the effects of these genes are small and
      may be related to population composition.

PMID- 21714070
TI  - Functional assessment of a promoter polymorphism in S100B, a putative risk
      variant for bipolar disorder.
AB  - Calcium-binding protein S100B has been implicated in the pathology of bipolar
      affective disorder (BPAD) and schizophrenia (SZ). S100B protein levels are
      elevated in serum of patients with both disorders compared to controls. We
      previously reported genetic association of a SNP in the promoter of S100B,
      rs3788266, with a psychotic form of BPAD. To test for genotypic effects of
      rs3788266 in vivo, S100B serum protein levels were measured in 350 Irish and
      German subjects of known S100B genotype. The functional effect of rs3788266 on
      S100B promoter activity was studied using the luciferase reporter system in
      U373MG glioblastoma and SH-SY5Y neuroblastoma cell lines. Allelic effects of
      rs3788266 on protein complex formation at the S100B promoter were investigated by
      an electrophoretic mobility shift assay. Higher mean serum S100B levels were
      associated with the risk G allele of rs3788266 in BPAD cases (P = 0.0001),
      unaffected relatives of BPAD cases (P < 0.0001) and unrelated controls (P <
      0.0001). Consistent with the in vivo findings, luciferase gene expression was
      significantly increased in the presence of the G allele compared to the A allele
      in SH-SY5Y (P = <0.0001), and in U373MG (P = <0.0008) cell lines. The binding
      affinity of both SH-SY5Y and U373MG protein complexes for the S100B promoter was
      significantly stronger in the presence of G allele compared to the A allele
      promoter fragments. These data support rs3788266 as a functional promoter variant
      in the S100B gene where the presence of the G allele promotes increased gene
      expression and is associated with increased serum levels of the protein.

PMID- 21714071
TI  - ATP13A2 variability in Taiwanese Parkinson's disease.
AB  - Mutations in ATP13A2 have been reported to associate with Parkinson's disease
      (PD). This study investigates the contribution of genetic variants in ATP13A2 to
      Taiwanese PD. ATP13A2 cDNA fragments from 65 early onset PD (onset <50 years)
      were sequenced. The identified variants were validated in a cohort of PD (n =
      493) and ethnically matched controls (n = 585). A novel heterozygous G1014S,
      located at the conserved seventh transmembrane domain of ATP13A2 protein, was
      identified in an early onset PD patient, which was absent in 585 normal controls.
      Additionally, a reported heterozygous A746T was found in two PD patients and four
      controls. The clinical features and 99mTc-TRODAT-1 single photon emission
      computed tomography (SPECT) image of the patients carrying G1014S and A746T were
      similar to that of idiopathic PD. One normal control with A746T showed an
      asymmetric reduction of 99mT TRODAT-1 uptake in the right striatum. Under
      oxidative stress or apoptotic stimulus, lymphoblastoid cells carrying either
      A764T or G1014S showed increased caspase 3 activity compared with the controls.
      The rates of decay for G1014S and A746T proteins were more or less reduced in
      cycloheximide chase experiment. In silico modeling of G1014S exhibited a more
      stable feature than wild-type, and G1014S is mislocalized mainly in the
      intralysosomal space, which is coherent with the prediction of prohibiting N
      myristoylation and membrane association. We therefore hypothesize that rare
      variants of ATP13A2 may contribute to PD susceptibility in Taiwan. The role
      played by ATP13A2 variants in PD remains to be clarified.

PMID- 21714072
TI  - Differential immune system DNA methylation and cytokine regulation in post
      traumatic stress disorder.
AB  - DNA methylation may mediate persistent changes in gene function following chronic
      stress. To examine this hypothesis, we evaluated African American subjects
      matched by age and sex, and stratified into four groups by post-traumatic stress
      disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was
      also assessed in all subjects. We evaluated DNA extracted from peripheral blood
      using the HumanMethylation27 BeadChip and analyzed both global and site-specific
      methylation. Methylation levels were examined for association with PTSD, child
      abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip
      effects. Global methylation was increased in subjects with PTSD. CpG sites in
      five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in
      subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS
      after adjustment for multiple testing. Notably, many of these genes have been
      previously associated with inflammation. Given these results and reports of
      immune dysregulation associated with trauma history, we compared plasma cytokine
      levels in these subjects and found IL4, IL2, and TNFalpha levels associated with
      PTSD, child abuse, and TLS. Together, these results suggest that psychosocial
      stress may alter global and gene-specific DNA methylation patterns potentially
      associated with peripheral immune dysregulation. Our results suggest the need for
      further research on the role of DNA methylation in stress-related illnesses.

PMID- 21714073
TI  - Isocyanate-functional adhesives for biomedical applications. Biocompatibility and
      feasibility study for vascular closure applications.
AB  - Biodegradable isocyanate-functional adhesives based on poly(ethylene glycol)
      adipic acid esters were synthesized, characterized, and evaluated in vitro and in
      vivo. Two types of formulations, P2TT and P2MT, were developed by
      functionalization with 2,4-tolylene diisocyanate (TDI) or 4,4'-methylene
      bis(phenyl isocyanate) (MDI), respectively, and branching with 1,1,1
      trimethylolpropane (TMP). The biocompatibility of the synthesized adhesive
      formulations was evaluated as per ISO 10993. Cytotoxicity, systemic toxicity,
      pyrogenicity, genotoxicity (reverse mutation of Salmonella typhimurium and
      Escherichia coli), hemolysis, intracutaneous reactivity, and delayed-type
      hypersensitivity were evaluated. All formulations met the requirements of the
      conducted standard tests. The biological behavior and ability of the adhesive
      formulations to close an arteriotomy and withstand arterial pressure following
      partial approximation with a single suture were evaluated in a rat abdominal
      aorta model. Animals were evaluated at 1, 2, 3, and 4 weeks after surgery.
      Macroscopic and histopathologic evaluation of explanted arteries suggested that
      the P2TT formulation had better in vivo performance than the P2MT formulation.
      Additionally, the P2TT formulation resulted in less tissue reaction than P2MT
      formulation. To our knowledge, this is the first study demonstrating the
      potential of this new class of isocyanate-functional degradable adhesives for
      vascular applications.

PMID- 21714074
TI  - A new approach in self-etching adhesive formulations: replacing HEMA for
      surfactant dimethacrylate monomers.
AB  - This study evaluated the influence of surfactant dimethacrylates (SD) on the
      resin-to-dentin microtensile bond strength (MUTBS) and characterized the
      interfacial micromorphology of the hybrid layer of the experimental HEMA-free
      self-etching systems. Five experimental HEMA-free two-step self-etching systems
      containing different SD (Bis-EMA 10, Bis-EMA 30, PEG 400, PEG 1000, and PEG 400
      UDMA) and a HEMA-containing system (control) were compared. Each experimental
      adhesive system was applied and resin composite restorations were incrementally
      built up in bovine incisors. After 24 h, restored teeth were sectioned to obtain
      24 sticks per group. Thereafter, the specimens were subjected to the MUTBS test.
      Data (MPa) were analyzed by One-way ANOVA and Tukey's test. Adhesive-dentin
      interfaces were analyzed through Scanning Electron Microscopy (SEM). The adhesive
      system formulated with PEG 400 UDMA produced MUTBS similar to the HEMA-containing
      group and statistically higher than the HEMA-free groups. Similar failure
      percentages were observed in the PEG 400 UDMA and the control group. In the SEM
      analysis, all the adhesive systems presented similar partially demineralized
      hybrid layer (1.5-3.0 MUm thickness) with well-formed resin tags. All SD
      presented reasonable initial MUTBS, with the PEG 400 UDMA being a promising
      monomer to be considered as a HEMA substitute in adhesive systems compositions.

PMID- 21714075
TI  - Preparation, structure, and in vitro chemical durability of yttrium phosphate
      microspheres for intra-arterial radiotherapy.
AB  - Chemically durable microspheres containing yttrium and/or phosphorus are useful
      for intra-arterial radiotherapy. In this study, we attempted to prepare yttrium
      phosphate (YPO4) microspheres with high chemical durability. YPO4 microspheres
      with smooth surfaces and diameters of around 25 MUm were successfully obtained
      when gelatin droplets containing yttrium and phosphate ions were cooled and
      solidified in a water-in-oil emulsion and then heat-treated at 1100 degrees C.
      The chemical durability of the heat-treated microspheres in a simulated body
      fluid at pH = 6 and 7 was high enough for clinical application of intra-arterial
      radiotherapy.

PMID- 21714076
TI  - Mechanical stability of two-step chemically deposited hydroxyapatite coating on
      Ti substrate: effects of various surface pretreatments.
AB  - The success of implants in orthopaedic and dental load-bearing applications
      crucially depends on the initial biological fixation of implants in surrounding
      bone tissues. Using hydroxyapatite (HA) coating on Ti implant as carrier for bone
      morphogenetic proteins (BMPs) may promote the osteointegration of implants;
      therefore, reduce the risk of implant failure. The goal of this study was to
      develop an HA coating method in conditions allowing the incorporation of protein
      based drugs into the coating materials, while achieving a mechanical stable
      coating on Ti implant. HA coatings were deposited on six different groups of Ti
      surfaces: control (no pretreatment), pretreated with alkali, acid, heat at 800
      degrees C, grit blasted with Al2O3, and grit blasted followed by heat treatment.
      HA coating was prepared using a two-step procedure. First step was the chemical
      deposition of a monetite coating on Ti substrate in acidic condition at 75
      degrees C and the second step was the hydrolysis of the monetite coating to HA.
      Coatings were characterized by scanning electron microscope (SEM), energy
      dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). The roughness
      of substrates and coatings was measured using profilometry technique. The
      mechanical stability of the coatings deposited on the pretreated substrates was
      assessed using scratch test. The coatings deposited on the grit-blasted Ti
      surface demonstrated superior adhesive properties with critical shearing stress
      131.6 +/- 0.2 MPa.

PMID- 21714077
TI  - Biocompatibility of magnesium particles evaluated by in vitro cytotoxicity and
      genotoxicity assays.
AB  - Mg is a biodegradable biomaterial which may release particles (MP) to the
      environment. The possible cyto- and genotoxic effects of MP derived from
      magnesium powder (mesh 325) were analyzed on rat osteosarcoma UMR106 cells in
      order simulate the effect of Mg debris. Neutral red (NR) incorporation and
      acridine orange/ethidium bromide (AO/EB) staining techniques were used as
      endpoints to analyze the cytotoxic effects at 25-1000 MUg/mL concentration range.
      Genotoxicity was estimated according to micronucleus (MN) formation and the Comet
      assay (CA). Results showed that MP size changes with time due to corrosion.
      Changes in lysosomal activity were observed after 24 h only at 1000 MUg/mL.
      Accordingly, AO/EB staining showed a significant decrease in the number of living
      cells at 500 MUg/mL. Transmission electronic microscopy showed MP internalization
      (60 and 200 nm diameter) in cells after 2-h treatment, whereas no MP was detected
      after 24 h. A significant dose-dependent increase in MN frequencies was observed
      at 25-100 MUg/mL range (nontoxic range). DNA damage induction was assessed by CA
      only at 500 MUg/mL. Results showed dose-dependent cytotoxic and genotoxic effects
      of MP on UMR106 cells with different threshold values of MP concentration.

PMID- 21714078
TI  - A completely autologous valved conduit prepared in the open form of trileaflets
      (type VI biovalve): mold design and valve function in vitro.
AB  - In-body tissue, architecture technology represents a promising approach for the
      development of living heart valve replacements and preparation of a series of
      biovalves. To reduce the degree of regurgitation and increase the orifice ratio,
      we designed a novel mold for a type VI biovalve. The mold had an outer diameter
      of 14 mm for implantation in beagles, and it was prepared by assembling two
      silicone rods with a small aperture (1 mm) between them. One rod had three
      protrusions of the sinus of Valsalva, whereas the other was almost cylindrical.
      When the molds were embedded in the subcutaneous pouches of beagles for 1 month,
      the native connective tissues that subsequently developed covered the entire
      outer surface of the molds and migrated into the aperture between the rods. The
      mold from both sides of the harvested cylindrical implant was removed, and
      homogenous well-balanced trileaflets were found to be separately formed in the
      open form with a small aperture at the three commissure parts inside the
      developed conduit, which had a thick homogenous wall even in the sinus of
      Valsalva. Exposure of the obtained biovalves to physiological aortic valve flow
      in beagles revealed proper opening motion with a wide orifice area. The closure
      dynamics were suboptimal, probably due to the reduction in the size of the sinus
      of Valsalva. The mechanical behavior of this biovalve might allow its use as a
      living aortic valve replacement.

PMID- 21714079
TI  - Development and in vitro studies of a polyethylene terephthalate-gold
      nanoparticle scaffold for improved biocompatibility.
AB  - Polyethylene terephthalate (PET) mesh is one of the most commonly used synthetic
      biomaterials for tension-free hernia repair. In an effort to improve the
      biocompatibility of PET mesh, gold nanoparticles (AuNP) in various concentrations
      were conjugated to the PET surface to develop PET-AuNP scaffolds. These novel
      scaffolds were characterized with Fourier transform infrared spectroscopy (FT
      IR), scanning electron microscopy (SEM), and differential scanning calorimetry
      (DSC) to assess the addition of functional groups, presence of AuNPs, and thermal
      stability of the modified PET mesh, respectively. The biocompatibility of the PET
      AuNP scaffolds was evaluated through in vitro cell culture assays. The
      cellularity of cells exposed to the PET-AuNP scaffolds, as well as the scaffolds'
      ability to reduce reactive oxygen species, was assessed using L929 murine
      fibroblasts. Antimicrobial properties of AuNPs conjugated to PET mesh were tested
      against the bacteria Pseudomonas aeruginosa. Results from the FT-IR showed
      presence of COOH groups while SEM displayed bonding of AuNPs to the PET surface.
      DSC results indicated that the PET more than likely did not undergo any
      detrimental degradation due to the surface modification. Results from the in
      vitro studies showed that AuNPs, in optimal concentrations (1* concentrations),
      enhanced cellularity, reduced ROS, and reduced bacteria adhesion to PET. These
      studies demonstrated enhanced biocompatibility of the AuNP conjugated PET mesh
      over pristine PET mesh.

PMID- 21714080
TI  - Synthesis of spherical hydroxyapatite granules with interconnected pore channels
      using camphene emulsion.
AB  - The aim of this study was to fabricate porous spherical hydroxyapatite (HA)
      granules with interconnected pore channels for use as a bone graft substitute.
      Various weights of camphene porogen were mixed with nano-sized HA powder
      (camphene/HA = 0, 10, 30, 50, 70, and 90% w/w) and 10% gelatin aqueous solution
      then added to the mixture. The water-in-oil emulsion method was employed to
      obtain spherical-shaped granules, of which those 1000-2000 MUm in diameter were
      selectively classified using a standard sieve set. Thermogravimetric analysis and
      X-ray diffraction were used to determine optimal sintering conditions. The
      sintered granules were characterized using field emission-scanning electron
      microscopy (FE-SEM), microcomputed tomography, and porosimetry. The pore size and
      porosity of spherical HA granules increased with the addition of camphene.
      Granules with a HA/camphene ratio of 90% (HG90) demonstrated macropores (>50 MUm)
      with interconnected pore channels (porosity: 58.49%). In addition, FE-SEM
      examination of HG90 coated with polycaprolactone showed that the granule may hold
      promise as a drug delivery carrier. We concluded that these HG90 granules merit
      consideration as a bone graft substitute or drug delivery carrier in bone tissue
      engineering.

PMID- 21714081
TI  - Comparative study of the viscoelastic mechanical behavior of agarose and
      poly(ethylene glycol) hydrogels.
AB  - This study presents a comparative investigation into differences in the
      mechanical properties between two hydrogels commonly used in cartilage tissue
      engineering [agarose vs. poly(ethylene glycol) (PEG)], but which are formed
      through distinctly different crosslinking mechanisms (physical vs. covalent,
      respectively). The effects of hydrogel chemistry, precursor concentration, platen
      type (nonporous vs. porous) used in compression bioreactors, and degradation (for
      PEG) on the swelling properties and static and dynamic mechanical properties were
      examined. An increase in precursor concentration resulted in decreased
      equilibrium mass swelling ratios but increased equilibrium moduli and storage
      moduli for both hydrogels (p < 0.05). Agarose displayed large stress relaxations
      and a frequency dependence indicating its viscoelastic properties. Contrarily,
      PEG hydrogels displayed largely elastic behavior with minimal stress relaxation
      and frequency dependence. In biodegradable PEG hydrogels, the largely elastic
      behavior was retained during degradation. The type of platen did not affect
      static mechanical properties, but porous platens led to a reduced storage modulus
      for both hydrogels implicating fluid flow. In summary, agarose and PEG exhibit
      vastly different mechanical behaviors; a finding largely attributed to
      differences in their chemistries and fluid movement. Taken together, these design
      choices (hydrogel chemistry/structure, loading conditions) will likely have a
      profound effect on the tissue engineering outcome.

PMID- 21714082
TI  - Characterization and preliminary in vivo evaluation of a novel modified
      hydroxyapatite produced by extrusion and spheronization techniques.
AB  - A glass-reinforced hydroxyapatite (HA) composite, recently registered as
      Bonelike(r), was developed for bone grafting. This biomaterial is composed of a
      modified HA matrix with alpha- and beta-tricalcium phosphate secondary phases and
      ionic species that mimic the chemical composition of human bone. Several in vitro
      and in vivo studies have confirmed the benefits of these properties. However,
      these studies were all executed with Bonelike(r) polygonal granules obtained by
      crushing. In this study, Bonelike(r) pellets were produced through a patented
      process, which required the use of techniques such as extrusion and
      spheronization. The final product presented a homogeneous size, a 55.1% global
      porosity and a spherical shape. This spherical shape permitted a better
      adaptation to the implantation site and improved injectability. Additionally, it
      also may contribute to formation of macropores as pellets packaging leaves open
      spaces. After implantation of Bonelike(r) polygonal granules and Bonelike(r)
      pellets in monocortical defects in sheep for 8 and 12 weeks, light microscopy and
      scanning electron microscopy showed extensive osteointegration simultaneously
      with bone regeneration for both presentations. Histomorphometric analysis did not
      reveal statistically significant differences between defects treated with
      Bonelike(r) polygonal granules and Bonelike(r) pellets, which suggests similar in
      vivo performances.

PMID- 21714083
TI  - Experimental and computational models to investigate the effect of adhesion on
      the mechanical properties of bone-cement composites.
AB  - A generic finite element approach was developed to study the effect of adhesion
      on the mechanical response of bone cement composites and validated against
      literature data. The results showed that a zero friction bone-cement (PMMA)
      interface conditions captured the results of the experimental testing better than
      assuming a fully bonded interface. An experimental model for studying the effect
      of interface adhesion in a bone-cement like composite was also developed in the
      present study. The results using this model indicate that the difference in
      Young's modulus and ultimate strength between a fully bonded interface and
      unbonded interface is approximately 30% for bone volume fraction similar to what
      can be found in osteoporotic vertebrae. Apart from concluding that bone to cement
      adhesion is a major contributor to the mechanical response of bone-cement
      composites, our studies based on the generic FE approach also indicate that the
      mechanical properties of the cement is the most important contributor to the
      resulting mechanical properties of the composite at bone volume fraction relevant
      in terms of vertebroplasty treatment.

PMID- 21714084
TI  - Surface characterization of Ti and Y-TZP following non-thermal plasma exposure.
AB  - Novel non-thermal plasma (NTP) technology has the potential to address the
      bonding issues of Y-TZP and Ti surfaces. This study aims to chemically
      characterize and evaluate the surface energy (SE) of Y-TZP and Ti surfaces after
      NTP application. Y-TZP and Ti discs were treated with a hand-held NTP device
      followed by SE evaluation. Spectra of Y-TZP 3d and Ti 2p regions, survey scans,
      and quantification of the elements were performed via X-ray photoelectron
      Spectroscopy (XPS) prior and after NTP. Separate Y-TZP and Ti discs were NTP
      treated for contact angle readings using (10-methacryloyloxydecyl
      dihydrogenphosphate) MDP primer. Significant augmentation of SE values was
      observed in all NTP treated groups. XPS detected a large increase in the O
      element fraction on both Y-TZP and Ti surfaces. Reduction of contact angle
      reading was obtained when the MDP primer was placed on NTP treated Y-TZP. Ti
      surface showed high SE before and after NTP application on Ti surfaces. NTP
      decreased C and increased O on both surfaces independently of application
      protocol. Wettability of MDP primer on Y-TZP was significantly increased after
      NTP. The high polarity obtained on Y-TZP and Ti surfaces after NTP applications
      appear promising to enhance bonds.

PMID- 21714085
TI  - Neomycin enhances extracellular matrix stability of glutaraldehyde crosslinked
      bioprosthetic heart valves.
AB  - Glutaraldehyde (GLUT) crosslinked porcine aortic heart valves are continued to be
      extensively used in heart valve replacement surgeries. GLUT does not crosslink
      glycosaminoglycans in the tissue and we have demonstrated that GAG loss is
      associated with tissue degeneration. In this study, we examined the ability of
      neomycin to enhance GLUT crosslinking to stabilize GAGs, as well as provide
      evidence of improved functional integrity. Neomycin enhanced GLUT crosslinked
      (NG) leaflets exposed to collagenase and elastase enzymes exhibited an increased
      resistance to proteolytic degradation. Furthermore, NG leaflets exhibited small
      but significant increases in collagen denaturation temperatures when compared to
      that of standard GLUT crosslinked BHVs. NG leaflets subjected to storage,
      accelerated cyclic fatigue, and in vitro enzyme mediated GAG degradation revealed
      improved GAG stabilization versus standard GLUT crosslinked valves, which
      sustained substantial decreases in GAG content. Ultrastructural analysis using
      transmission electron microscopy qualitatively confirmed NG leaflets preserved
      GAGs after enzymatic degradation. Biomechanical analyses demonstrated that NG
      leaflets were functionally similar to GLUT tissues but were slightly stiffer
      under both planar biaxial tension and under flexure. Interestingly, after GAGase
      treatment, GLUT tissues showed increased areal compliance and reduced hysteresis,
      while NG leaflets were unchanged. Collectively, NG cross-linking functionally
      insulated the tissue from GAG digestion, and imparted modest additional matrix
      stiffness but maintained tissue hysteresis properties.

PMID- 21714086
TI  - A synthesis route to nanoparticle dicalcium silicate for biomaterials research.
AB  - Dicalcium silicate (Ca2 SiO4) has been reported as an interesting candidate for
      biomaterials use due to its attractive bioactive properties. Here, we report on
      how dicalcium silicate was prepared by a sol-gel route using calcium nitrate
      tetrahydrate and tetraorthosilicate as the precursors chemicals for CaO and SiO2
      , respectively. The synthesized powders were characterized using
      thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),
      Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Brunauer
      Emmett-Teller (BET) method, scanning electron microscopy (SEM), and transmission
      electron microscopy (TEM). High purity dicalcium silicate at a CaO/SiO2 molar
      ratio of 2:1 could be formed by the sol-gel method without a washing process and
      was then calcined at 800 degrees C. The effects of the molar ratio of CaO/SiO2 ,
      the washing process, and the calcination temperature have been shown to affect
      the purity, the formation, and the particle size of the nanoparticles, which have
      been investigated and discussed.

PMID- 21714087
TI  - Determination of the slow crack growth susceptibility coefficient of dental
      ceramics using different methods.
AB  - This study compared three methods for the determination of the slow crack growth
      susceptibility coefficient (n) of two veneering ceramics (VM7 and d.Sign), two
      glass-ceramics (Empress and Empress 2) and a glass-infiltrated alumina composite
      (In-Ceram Alumina). Discs (n = 10) were prepared according to manufacturers'
      recommendations and polished. The constant stress-rate test was performed at five
      constant stress rates to calculate n(d) . For the indentation fracture test to
      determine n(IF) , Vickers indentations were performed and the crack lengths were
      measured under an optical microscope. For the constant stress test (performed
      only for d.Sign for the determination of n(s) ) four constant stresses were
      applied and held constant until the specimens' fracture and the time to failure
      was recorded. All tests were performed in artificial saliva at 37 degrees C. The
      n(d) values were 17.2 for Empress 2, followed by d.Sign (20.5), VM7 (26.5),
      Empress (30.2), and In-Ceram Alumina (31.1). In-Ceram Alumina and Empress 2
      showed the highest n(IF) values, 66.0 and 40.2, respectively. The n(IF) values
      determined for Empress (25.2), d.Sign (25.6), and VM7 (20.1) were similar. The
      n(s) value determined for d.Sign was 31.4. It can be concluded that the n values
      determined for the dental ceramics evaluated were significantly influenced by the
      test method used.

PMID- 21714088
TI  - Induction plasma sprayed Sr and Mg doped nano hydroxyapatite coatings on Ti for
      bone implant.
AB  - In this study, we report fabrication of strontium (Sr) and magnesium (Mg) doped
      hydroxyapatite (HA) coating on commercially pure titanium (Cp-Ti) substrates
      using inductively coupled radio frequency (RF) plasma spray. HA powder was doped
      with 1 wt % Sr (Sr-HA) and 1 wt % Mg (Mg-HA), heat treated at 800 degrees C for 6
      h and then used for plasma spray coating. X-ray diffraction (XRD) and Fourier
      transformed infrared spectroscopic (FTIR) analysis indicated that the coatings
      were primarily composed of phase pure crystalline HA. When compared to undoped HA
      coating, physical properties such as microstructure, grain size, and adhesive
      bond strength of the doped HA coatings did not change significantly.
      Microstructure of the coatings showed coherency in the structure with an average
      grain size of 200-280 MUm HA particles, where each of the HA grains consisted of
      20-30 nm sized particles. An average adhesive bond strength of 17 MPa ensured
      sufficient mechanical strength of the coatings. A chemistry dependent improvement
      in bone cell-coating interaction was noticed for doped coatings although it had
      minimal effect on physical properties of the coatings. In vitro cell-materials
      interactions using human fetal osteoblasts (hFOB) showed better cell attachment
      and proliferation on Sr-HA coatings compared to HA or Mg-HA coatings. Presence of
      Sr in the coating also stimulated hFOB cell differentiation and alkaline
      phosphatase (ALP) expression. Improvement in bioactivity of Sr doped HA coatings
      on Ti without compromising its mechanical properties makes it an excellent
      material of choice for coated implant.

PMID- 21714090
TI  - Corrosion of Mg alloy AZ91D in the presence of living cells.
AB  - Mg and Mg alloys are of interest for biodegradable implants as they readily
      corrode in biological fluids, and dissolved Mg ions are nontoxic. Even though it
      is well known that Mg dissolution leads to pH increase in the surroundings, the
      effect of the corrosion-induced alkalization on the biological environment has
      not been studied in detail. We therefore explored the interactions between
      corrosion-induced pH increase and cell growth on Mg alloy AZ91D surface. Cell
      adhesion and spreading on the alloy surface is unimpeded initially. However, with
      time a large fraction of cells de-adhere. We attribute this to the observed
      increase of the pH in the cell culture medium in the process of alloy
      dissolution. Cytotoxicity tests with HeLa cells grown on glass surfaces confirm
      that cell death increases with increasing alkalinity of the cell culture medium.
      We also show that a the cells that adhere on the Mg alloy surface act as a
      corrosion-blocking surface layer. In consequence, a slower pH increase in the
      medium takes place when the alloy surface is covered with cells. Electrochemical
      impedance spectroscopy measurements (EIS) verify that a cell layer slows down the
      corrosion process.

PMID- 21714093
TI  - Biphenyl sulfonylamino methyl bisphosphonic acids as inhibitors of matrix
      metalloproteinases and bone resorption.
AB  - A number of matrix metalloproteinases (MMPs), proteins important in the balance
      of bone remodeling, play a critical role both in cancer metastasis and in bone
      matrix turnover associated with the presence of cancer cells in bone. Here, we
      report the synthesis and biological evaluation of a new class of MMP inhibitors
      characterized by a bisphosphonate function as the zinc binding group. Since the
      bisphosphonate group is also implicated in osteoclast inhibition and provides a
      preferential affinity to biological apatite, the new molecules can be regarded as
      bone-seeking medicinal agents. Docking experiments were performed to clarify the
      mode of binding of bisphosphonate inhibitors in the active site of MMP-2. The
      most promising of the studied bisphosphonates showed nanomolar inhibition against
      MMP-2 and resulted in potent inhibition of osteoclastic bone resorption in vitro.

PMID- 21714095
TI  - Cell-free HIV-1 virucidal action by modified peptide triazole inhibitors of Env
      gp120.

PMID- 21714096
TI  - Warfarin glycosylation invokes a switch from anticoagulant to anticancer
      activity.

PMID- 21714097
TI  - Adamantyl ethanone pyridyl derivatives: potent and selective inhibitors of human
      11beta-hydroxysteroid dehydrogenase type 1.
AB  - Elevated levels of active glucocorticoids have been implicated in the development
      of several phenotypes of metabolic syndrome, such as type 2 diabetes and obesity.
      11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses the
      intracellular conversion of inactive cortisone to cortisol. Selective 11beta-HSD1
      inhibitors have shown beneficial effects in various conditions, including
      diabetes, dyslipidemia and obesity. A series of adamantyl ethanone pyridyl
      derivatives has been identified, providing potent and selective inhibitors of
      human 11beta-HSD1. Lead compounds display low nanomolar inhibition against human
      and mouse 11beta-HSD1 and are selective for this isoform, with no activity
      against 11beta-HSD2 and 17beta-HSD1. Structure-activity relationship studies
      reveal that an unsubstituted pyridine tethered to an adamantyl ethanone motif
      through an ether or sulfoxide linker provides a suitable pharmacophore for
      activity. The most potent inhibitors have IC50 values around 34-48 nM against
      human 11beta-HSD1, display reasonable metabolic stability in human liver
      microsomes, and weak inhibition of key human CYP450 enzymes.

PMID- 21714098
TI  - Solution-processable n-type organic field-effect transistor (OFET) materials
      based on carbonyl-bridged bithiazole and dioxocyclopentene-annelated thiophenes.
AB  - A series of electronegative pi-conjugated compounds composed of carbonyl-bridged
      bithiazole and alkyl-substituted dioxocyclopenta[b]thiophene were synthesized as
      a candidate for solution-processable n-type organic semiconductor materials and
      characterized on the basis of photophysical and electrochemical properties.
      Cyclic voltammetry measurements showed that the first half-wave reduction
      potentials of these compounds are between -0.97 and -1.14 V versus
      ferrocene/ferrocenium, which corresponds to lowest unoccupied molecular orbital
      energy levels between -3.83 and -3.66 eV. Thanks to hexyl or dodecyl groups in
      the molecules, the compounds are sufficiently soluble to realize the fabrication
      of their thin films through a spin-coating method. As a result, the prepared
      organic field-effect transistors based on these newly developed compounds
      exhibited n-channel characteristics not only under vacuum but also in air, and
      the best field-effect electron mobility observed under vacuum was 0.011 cm(2) V(
      1) s(-1) with an on/off ratio of 10(8) and a threshold voltage of 16 V.

PMID- 21714099
TI  - In vivo characterization of tumor and tumor vascular network using multi-modal
      imaging approach.
AB  - We present a multi-modal optical diagnostic approach utilizing a combined use of
      Fluorescence Intravital Microscopy (FIM), Dynamic Light Scattering (DLS) and
      Spectrally Enhanced Microscopy (SEM) modalities for in vivo imaging of tumor
      vascular network and blood microcirculation. FIM is used for imaging of tumor
      surroundings and microenvironment, SEM provides information regarding blood
      vessels topography, whereas DLS is applied for functional imaging of vascular
      network and blood microcirculation. This complementary combination of the imaging
      approaches is extremely useful for functional in vivo imaging of blood
      vasculature and tumor microenvironment. The technique has also a great potential
      in vascular biology and can significantly expand the capabilities of tumor
      angiogenesis studies and notably contribute to the development of cancer
      treatment.

PMID- 21714100
TI  - Glycerol hydrogenolysis promoted by supported palladium catalysts.
AB  - Catalytic hydrogenolysis, with high conversion and selectivity, promoted by
      supported palladium substrates in isopropanol and dioxane at a low H(2) pressure
      (0.5 MPa), is reported for the first time. The catalysts, characterized by using
      BET isotherms, transmission electron microscopy (TEM), temperature-programmed
      reduction (TPR), powder X-ray diffraction (XRD), and X-ray photoelectron
      spectroscopy (XPS), were obtained by coprecipitation and impregnation techniques.
      The coprecipitation method allows catalysts with a metal-metal or a metal-support
      interaction to be obtained, which enhances the catalytic performance for both the
      conversion of glycerol and the selectivity to 1,2-propanediol. Analogous
      reactions carried out with catalysts prepared by using impregnation are less
      efficient. A study of the solvent and temperature effect is also presented. The
      obtained results allow the hydrogenolysis mechanism to be inferred; this involves
      both the direct replacement of the carbon-bonded OH group by an incoming hydrogen
      or the formation of hydroxyacetone as an intermediate, which subsequently
      undergoes a hydrogenation process to give 1,2-propanediol. Finally, catalytic
      tests on a large-scale reaction at a higher H(2) pressure and recycling of the
      samples were carried out with the better performing catalysts (Pd/CoO and
      Pd/Fe(2)O(3) prepared by using coprecipitation) to verify possible industrial
      achievements.

PMID- 21714103
TI  - Induction of axon growth arrest without growth cone collapse through the N
      terminal region of four-transmembrane glycoprotein M6a.
AB  - During development, axons elongate vigorously, carefully controlling their speed,
      to connect with their targets. In general, rapid axon growth is correlated with
      active growth cones driven by dynamic actin filaments. For example, when the
      actin-driven tip is collapsed by repulsive guidance molecules, axon growth is
      severely impaired. In this study, we report that axon growth can be suppressed,
      without destroying the actin-based structure or motility of the growth cones,
      when antibodies bind to the four-transmembrane glycoprotein M6a concentrated on
      the growth cone edge. Surprisingly, M6a-deficient axons grow actively but are not
      growth suppressed by the antibodies, arguing for an inductive action of the
      antibody. The binding of antibodies clusters and displaces M6a protein from the
      growth cone edge membrane, suggesting that the spatial rearrangement of this
      protein might underlie the unique growth cone behavior triggered by the
      antibodies. Molecular dissection of M6a suggested involvement for the N-terminal
      intracellular domain in this antibody-induced growth cone arrest.

PMID- 21714101
TI  - Regulation of axonal outgrowth and pathfinding by integrin-ECM interactions.
AB  - Developing neurons use a combination of guidance cues to assemble a functional
      neural network. A variety of proteins immobilized within the extracellular matrix
      (ECM) provide specific binding sites for integrin receptors on neurons. Integrin
      receptors on growth cones associate with a number of cytosolic adaptor and
      signaling proteins that regulate cytoskeletal dynamics and cell adhesion. Recent
      evidence suggests that soluble growth factors and classic axon guidance cues may
      direct axon pathfinding by controlling integrin-based adhesion. Moreover, because
      classic axon guidance cues themselves are immobilized within the ECM and
      integrins modulate cellular responses to many axon guidance cues, interactions
      between activated receptors modulate cell signals and adhesion. Ultimately,
      growth cones control axon outgrowth and pathfinding behaviors by integrating
      distinct biochemical signals to promote the proper assembly of the nervous
      system. In this review, we discuss our current understanding how ECM proteins and
      their associated integrin receptors control neural network formation.

PMID- 21714104
TI  - Neonatal fluoxetine exposure alters motor performances of adolescent rats.
AB  - Growing evidence from human and animal studies has shown adverse consequences of
      maternal usage of antidepressants in their newborn babies. To study the effects
      of early antidepressant exposure on motor function later in life, we treated
      neonatal rat pups with fluoxetine (FLX), a selective serotonin reuptake inhibitor
      (SSRI)-type antidepressant, from the day of birth to postnatal day 4 and examined
      motor performance during adolescence. FLX-treated rats had reduced locomotor
      activities in an open field and poorer motor performance on an accelerating
      rotarod compared to the control group of saline-treated animals. Nevertheless,
      the poorer motor performance largely improved after repetitive practices. To
      elucidate the structural alterations in the motor system, we examined the
      structure of neurons in motor-related brain regions. The shape, density, and soma
      size of cerebellar Purkinje cells were comparable in the two groups, however,
      density of dendritic spine in medial spiny neurons of striatum and Layer 5
      pyramidal neurons in the primary motor cortex (M1) were reduced in FLX-rats.
      Furthermore, the basilar dendrites in M1 Layer 5 neurons had reduced dendritic
      complexity than those of the control animals. The impaired dendritic structure in
      striatal and cortical neurons in FLX-treated rats might account for their poorer
      motor performances. Together, the structure and function of the motor system are
      affected by early FLX exposure, the long-term effects of early exposure to SSRI
      type antidepressants should be concerned.

PMID- 21714102
TI  - Intracellular trafficking in Drosophila visual system development: a basis for
      pattern formation through simple mechanisms.
AB  - Intracellular trafficking underlies cellular functions ranging from membrane
      remodeling to receptor activation. During multicellular organ development, these
      basic cell biological functions are required as both passive machinery and active
      signaling regulators. Exocytosis, endocytosis, and recycling of several key
      signaling receptors have long been known to actively regulate morphogenesis and
      pattern formation during Drosophila eye development. Hence, intracellular
      membrane trafficking not only sets the cell biological stage for receptor
      mediated signaling but also actively controls signaling through spatiotemporally
      regulated receptor localization. In contrast to eye development, the role of
      intracellular trafficking for the establishment of the eye-to-brain connectivity
      map has only recently received more attention. It is still poorly understood how
      guidance receptors are spatiotemporally regulated to serve as meaningful synapse
      formation signals. Yet, the Drosophila visual system provides some of the most
      striking examples for the regulatory role of intracellular trafficking during
      multicellular organ development. In this review we will first highlight the
      experimental and conceptual advances that motivate the study of intracellular
      trafficking during Drosophila visual system development. We will then illuminate
      the development of the eye, the eye-to-brain connectivity map and the optic lobe
      from the perspective of cell biological dynamics. Finally, we provide a
      conceptual framework that seeks to explain how the interplay of simple
      genetically encoded intracellular trafficking events governs the seemingly
      complex cellular behaviors, which in turn determine the developmental product.

PMID- 21714105
TI  - Ovarian stem cell niche and follicular renewal in mammals.
AB  - Stem cell niche consists of perivascular compartment, which connects the stem
      cells to the immune and vascular systems. During embryonic period, extragonadal
      primordial germ cells colonize coelomic epithelium of developing gonads.
      Subsequently, ovarian stem cells (OSC) produce secondary germ cells under the
      influence of OSC niche, including immune system-related cells and hormonal
      signaling. The OSC in fetal and adult human ovaries serve as a source of germ and
      granulosa cells. Lack of either granulosa or germ cell niche will result in
      premature ovarian failure in spite of the presence of OSC. During perinatal
      period, the OSC transdifferentiate into fibroblast-like cells forming the ovarian
      tunica albuginea resistant to environmental threats. They represent mesenchymal
      precursors of epithelial OSC during adulthood. The follicular renewal during the
      prime reproductive period (PRP) ensures that there are fresh eggs available for a
      healthy progeny. End of PRP is followed by exponentially growing fetal genetic
      abnormalities. The OSC are present in adult, aging, and postmenopausal ovaries,
      and differentiate in vitro into new oocytes. During in vitro development of large
      isolated oocytes reaching 200 MUm in diameter, an ancestral mechanism of
      premeiotic nurse cells, which operates during oogenesis in developing ovaries
      from invertebrates to mammalian species, is utilized. In vitro developed eggs
      could be used for autologous IVF treatment of premature ovarian failure. Such
      eggs are also capable to produce parthenogenetic embryos like some cultured
      follicular oocytes. The parthenotes produce embryonic stem cells derived from
      inner cell mass, and these cells can serve as autologous pluripotent stem cells.

PMID- 21714106
TI  - Cross- and triple-ratios of human body parts during development.
AB  - Recently developed landmark-based geometric morphometry has been used to depict
      the morphological development of organisms. In geometry, four landmarks can be
      mapped to any other four by Mobius transformations, if the cross-ratio of the
      landmarks is invariant and vice versa. To geometrically analyze the morphological
      development of the human body, we examined the cross-ratio of three consecutive
      body parts that are segmented by four landmarks in their configuration. Moreover,
      we introduced the triple-ratio of five landmarks that segments four consecutive
      parts (e.g., the shoulder, upper arm, forearm, and hand) and examined their
      growth patterns. The cross- and triple-ratios of the upper limb and shoulder
      girdle in fetuses were constant when biomechanical landmarks were used, although
      the cross-ratio of the upper limb varied when anatomical landmarks were used. The
      cross-ratios of the lower limbs, trunk, and pelvic girdles in fetuses differed
      from their corresponding cross-ratios in adults. These results suggest Mobius
      growth in the fetal upper limb and shoulder girdle but not in the other body
      parts examined. However, the growth balance of the three contiguous body parts
      was represented by the developmental change in the cross-ratio. Therefore, the
      cross- and triple-ratios may be applicable for simple but significant assessments
      of growth balance or proportion of the body parts.

PMID- 21714107
TI  - Paleoneurology of two new neandertal occipitals from El Sidron (asturias, Spain)
      in the context of homo endocranial evolution.
AB  - The endocranial surface description and comparative analyses of two new
      neandertal occipital fragments (labelled SD-1149 and SD-370a) from the El Sidron
      site (Asturias, Spain) reveal new aspects of neandertal brain morphological
      asymmetries. The dural sinus drainage pattern, as observed on the sagittal
      transverse system, as well as the cerebral occipito-petalias, point out a
      slightly differential configuration of the neandertal brain when compared to
      other Homo species, especially H. sapiens. The neandertal dural sinus drainage
      pattern is organized in a more asymmetric mode, in such a way that the superior
      sagittal sinus (SSS) drains either to the right or to the left transverse
      sinuses, but in no case in a confluent mode (i.e. simultaneous continuation of
      SSS with both right (RTS) and left (LTS) transverse sinuses). Besides, the
      superior sagittal sinus shows an accentuated deviation from of the mid-sagittal
      plane in its way to the RTS in 35% of neandertals. This condition, which
      increases the asymmetry of the system, is almost nonexistent neither in the
      analyzed Homo fossil species sample nor in that of anatomically modern humans.
      Regarding the cerebral occipito-petalias, neandertals manifest one of the lowest
      percentages of left petalia of the Homo sample (including modern H. sapiens). As
      left occipito-petalia is the predominant pattern in hominins, it seems as if
      neandertals would have developed a different pattern of brain hemispheres
      asymmetry. Finally, the relief and position of the the cerebral sulci and gyri
      impressions observed in the El Sidron occipital specimens look similar to those
      observed in modern H. sapiens.

PMID- 21714108
TI  - High-intensity resistance training with insufficient recovery time between bouts
      induce atrophy and alterations in myosin heavy chain content in rat skeletal
      muscle.
AB  - The aim of this study was to test whether high-intensity resistance training with
      insufficient recovery time between bouts, could result in a decrease of muscle
      fiber cross-sectional area (CSA), alter fiber-type frequencies and myosin heavy
      chain (MHC) isoform content in rat skeletal muscle. Wistar rats were divided into
      two groups: trained (Tr) and control (Co). Tr group were subjected to a high
      intensity resistance training program (5 days/week) for 12 weeks, involving jump
      bouts into water, carrying progressive overloads based on percentage body weight.
      At the end of experiment, animals were sacrificed, superficial white (SW) and
      deep red (DR) portions of the plantaris muscle were removed and submitted to
      mATPase histochemical reaction and SDS-PAGE analysis. Throughout the experiment,
      both groups increased body weight, but Tr was lower than Co. There was a
      significant reduction in IIA and IID muscle fiber CSA in the DR portion of Tr
      compared to Co. Muscle fiber-type frequencies showed a reduction in Types I and
      IIA in the DR portion and IID in the SW portion of Tr compared to Co; there was
      an increase in Types IIBD frequency in the DR portion. Change in muscle fiber
      type frequency was supported by a significant decrease in MHCI and MHCIIa
      isoforms accompanied by a significant increase in MHCIIb isoform content. MHCIId
      showed no significant differences between groups. These data show that high
      intensity resistance training with insufficient recovery time between bouts
      promoted muscle atrophy and a transition from slow-to-fast contractile activity
      in rat plantaris muscle.

PMID- 21714109
TI  - Age-associated changes of the mandibular foramen position in anteroposterior
      dimension and of the mandibular angle in dry human mandibles.
AB  - The effect of age on the anteroposterior (A-P) position of the mandibular foramen
      (MF) and on the size of the gonial angle (GA) was evaluated in this study. From
      an Israeli Bedouin population, 121 dry mandibles with primary (36), mixed (26),
      and permanent dentitions (59) were analyzed. The A-P position of the MF
      perpendicular to the posterior border of the ramus was measured with a digital
      caliper. A mandibulometer was used to evaluate the GA. The MF distance from the
      posterior border of the ramus increased significantly with age by 66% from
      primary (7.75 mm) to permanent (12.9 mm; P < 0.001). Similarly, the MF distance
      from the posterior border of the ramus relative to the total ramus width in A-P
      dimension increased significantly (21.4%) with altered dentitions from primary
      (0.28) to late permanent dentition (0.34; P < 0.001). The GA decreased
      significantly with age from 140.17 degrees  +/- 5.9 degrees  (primary dentition)
      to 123.61 degrees  +/- 6.9 degrees  (late permanent dentition; P < 0.001). The
      anterior movement of the MF and the decreased size of the GA that occurred with
      changing dentition were related to growth process. The MF moves anteriorly, and
      the GA decreases with age.

PMID- 21714110
TI  - Development of embryonic gill vasculature in the yellow stingray, Urobatis
      jamaicensis.
AB  - Corrosion casting was utilized to examine the development of gill vasculature in
      embryonic yellow stingrays, Urobatis jamaicensis (formerly Urolophus
      jamaicensis). The most marked changes in vascular configuration of the gills
      occur in the earliest castable stages of gestation. These changes included
      development of afferent external gill filament vessels and progression from
      paired dorsal aortae to a single fused dorsal aorta. Internal gill vasculature
      was found to nearly match that of an adult by the time the external gill
      filaments had fully regressed and yolk sac had been exhausted (>47 mm disc
      width). Examination of embryo casts also revealed characteristics of the
      branchial vasculature not previously reported in adult specimens. These include
      the presence of pre-lamellar sphincters, intertrematic branches, afferent
      distributing arteries, which supply blood to many afferent filament arteries
      resulting in greater interconnection of the filaments, and observation that the
      afferent branchial artery in the first hemibranch supplies blood directly to
      afferent filament arteries on the dorsal half of this arch.

PMID- 21714111
TI  - Volumetric analysis of the African elephant ventricular system.
AB  - This study used magnetic resonance imaging (MRI) to determine the volume of the
      ventricular system in the brain of three adult male African elephants (Loxodonta
      africana). The ventricular system of the elephant has a volume of ~240 mL, an
      order of magnitude larger than that seen in the adult human. Despite this large
      size, allometric analysis indicates that the volume of the ventricles in the
      elephant is what one would expect for a mammal with an ~5 kg brain.
      Interestingly, our comparison with other mammals revealed that primates appear to
      have small relative ventricular volumes, and that megachiropterans and
      microchiropterans follow different scaling rules when comparing ventricular
      volume to brain mass indicating separate phylogenetic histories. The current
      study provides context for one aspect of the elephant brain in the broader
      picture of mammalian brain evolution.

PMID- 21714112
TI  - Shrinkage of renal tissue after impregnation via the cold Biodur plastination
      technique.
AB  - Thorough dehydration is a key for good plastination and invariably it leads to
      shrinkage. Shrinkage during plastination has been studied to lesser extent.
      Shrinkage was studied in 10 pig kidneys including regional shrinkage (cortex,
      medulla, sinus) and at which stages of the process (dehydration, impregnation,
      curing) shrinkage occurred. Kidneys were fixation by perfusion of 10% neutral
      buffered formalin solution via the renal artery. The vessels and ureter were
      filled with colored silicone (Dow Corning, Silastic E RTV Silicone Rubber) and
      the kidneys were cut into one centimeter transverse slices. Two slices of each
      kidney were plastinated via the classic von Hagens' method. Slices were
      photographed at the same focal length after preparation and at the end of each
      stage of plastination. Slice surface area was determined by a point-counting
      planimetry method. Post dehydration shrinkage of the kidney was 10.21% while post
      impregnation 10.11%. After completion of plastination, total area of kidney slice
      shrinkage was 19.72%. Cortical area shrunk 12.81% after dehydration and 13.16%
      after impregnation. After plastination, cortical area had shrunk 24.28%. No
      significant shrinkage occurred in the medulla and sinus. Results demonstrate that
      kidney shrinkage during impregnation is as intense as during dehydration.
      Significant shrinkage occurred in the renal cortex but not in the medulla and
      sinus. This demonstrates that different tissue types, even in the same specimen,
      have different rates of shrinkage during dehydration and impregnation. Therefore,
      plastinated specimens should be used carefully in research where obtaining
      measures is important.

PMID- 21714113
TI  - Expression of mortalin detected in human liver cancer by tissue microarrays.
AB  - Mortalin is a highly conserved molecular chaperone in the heat shock protein
      (HSP) 70 family, which plays a role in carcinogenesis. The relationship between
      tumors and the expression of mortalin is not fully elucidated. In this study,
      human tumor specimens from various organs of liver cancer at different stages and
      cultured liver cancer cells were used to study the expression pattern of
      mortalin. Through immunohistochemistry we showed that mortalin was significantly
      higher in tumors than in adjacent benign tissues. Using liver tissue microarrays
      tested on hepatocellular carcinomas, mortalin expression was consecutively higher
      with advanced tumor stages. Mortalin expression on the cultured liver cancer
      cells were characterized with immunocytochemistry, Real-time PCR, and western
      blot. The results showed that the expression level is markedly higher in the SMMC
      7721 (a liver-derived tumor cell line) than in the HL 7702 (a normal liver cell
      line) in the protein level only. Understanding the role of mortalin in tumors may
      lead to development of a new therapeutic target in cancer treatment.

PMID- 21714114
TI  - Letter to the editor: genetic instability in the downregulation of sFRP1.

PMID- 21714115
TI  - Effects of advanced age on the morphometry and degenerative state of the cervical
      spine in a rat model.
AB  - Aging causes changes in the geometry of the human cervical spine that may
      influence the tissue response to applied loads. Rat models are often used to
      study spinal cord injuries (SCI) and have the potential to enhance our
      understanding of the effect of age on SCI. The goal of this study was to
      characterize the morphometry and degenerative state of the cervical spine in
      Fisher 344 rats, and to determine the influence of age on these variables.
      Fifteen rats were split into three age groups: young adult (3 months of age),
      aged (12-18 months) and geriatric (30 months). Following tissue harvest we used a
      MUCT scanner to image the cervical and upper thoracic spine from each specimen.
      Analysis software was used to measure variables including canal pinch diameter
      (the most rostral point on the dorsal aspect of a vertebral body to the most
      caudal aspect of the lamina on the immediately rostral vertebra), vertebral canal
      depth, width, and area, vertebral body height, depth, width, and area, and
      intervertebral disc thickness. Orthopaedic surgeons used midsagittal images to
      rate the degenerative state of the intervertebral discs. For all measures except
      disc thickness there was a significant increase (mean (SD) = 15.0 (9.7)%) for the
      aged compared to young specimens (P < 0.05). There were significant differences
      between the aged and geriatric specimens for only vertebral body depth (P =
      0.016) and area (P = 0.020). Intervertebral disc degeneration was significantly
      greater on the ventral aspect of the spinal column (P < 0.001), with a trend
      toward increased degeneration in the geriatric specimens (P = 0.069). The results
      suggest that age-related morphometric differences may need to be accounted for in
      experimental aging models of SCI in rats.

PMID- 21714116
TI  - Increased expression of sodium channel subunit Nav1.1 in the injured dorsal root
      ganglion after peripheral nerve injury.
AB  - The mechanisms underlying neuropathic pain induction are very complex but might
      involve abnormal spontaneous activity in the sensory dorsal root ganglion (DRG).
      Voltage-gated sodium channels in the DRG are essential for the genesis of
      abnormal spontaneous neuronal activity. In this study, we examined the changes in
      expression of the voltage-gated sodium channel Nav1.1 in the DRG after peripheral
      nerve injury. Western blot analysis showed that the level of Nav1.1 protein in
      the ipsilateral L5 DRG was significantly increased on Days 3 and 7 after fifth
      lumbar spinal nerve ligation. Immunohistochemical study further confirmed a
      marked increase in the percentage of Nav1.1-positive cells in the ipsilateral DRG
      on Day 3 after fifth lumbar spinal nerve ligation. Similarly, on Day 7 after
      sciatic nerve axotomy, the amount of Nav1.1 protein and the percentage of Nav1.1
      positive cells in the ipsilateral L5 DRG were also significantly increased. Our
      results suggest that an early increase in DRG Nav1.1 expression after peripheral
      nerve injury might be involved in the induction of neuropathic pain.

PMID- 21714117
TI  - Extrahepatic and intrahepatic human portal interstitial Cajal cells.
AB  - Portal interstitial cells of Cajal (PICCs), acting as vascular pacemakers, were
      previously only identified in nonhumans. Moreover, there is no evidence available
      about the presence of such cells within the liver. The objective of the study is
      to evaluate whether or not PICCs are identifiable in humans and, if they are,
      whether or not they are following the scaffold of portal vein (PV) branches
      within the liver. We obtained extrahepatic PVs and liver samples from six adult
      human cadavers, negative for liver disease, in accordance with ethical rules.
      They were stained with hematoxylin-eosin (HE) and Giemsa, and then we performed
      immunohistochemistry on formalin-fixed paraffin-embedded specimens for CD117/c
      kit, a marker of the Cajal's cells. Immune labeling was also performed for S-100
      protein, desmin, glial fibrillary acidic protein (GFAP), neurofilaments, alpha
      smooth muscle actin (alpha-SMA), and CD34. c-kit-Positive PICCs were identified
      within the extrahepatic PV, in portal spaces, and septa. On adjacent sections,
      these PICCs were negative for all the other antibodies used. In conclusion, our
      study confirms the presence of extrahepatic PICCs on humans, which may act as a
      possible intrinsic pacemaker in the human PV. However, the intrahepatic PICCs,
      which were evidenced here for the first time, are in need for further
      experimental studies to evaluate their functional role. A promising further
      direction of the study is the PICCs role in the idiopathic portal hypertension.

PMID- 21714118
TI  - Rubredoxin reductase from Alcanivorax borkumensis: expression and
      characterization.
AB  - Oil pollution is an environmental problem of increasing importance. Alcanivorax
      borkumensis, with a high potential for biotechnological applications, is a key
      marine hydrocarbonoclastic bacterium and plays a critical role in the
      bioremediation of oil-polluted marine systems. In oil degrading bacteria, the
      first step of alkane degradation is catalyzed by a monooxygenase. The reducing
      electrons are tunneled from NAD(P)H via rubredoxin, one of the most primitive
      metalloproteins, to the hydroxylase. Rubredoxin reductase is a flavoprotein
      catalyzing the reduction of rubredoxin. There are two rubredoxin genes, alkG and
      rubA, in A. borkumensis genome. In this work, the genes encoding rubredoxin
      reductase (ABO_0162, rubB) and AlkG(ABO_2708, alkG) were cloned and functionally
      overexpressed in E. coli. Our results demonstrate that RubB could reduce AlkG,
      therefore compensating for the absence of AlkT, also a rubredoxin reductase,
      missing in A. borkumensis SK2 genome. These results will increase our knowledge
      concerning biological alkane degradation and will lead us to design more
      efficient biotransformation and bioremediation systems.

PMID- 21714119
TI  - Medication management--the missing link in dementia interventions.

PMID- 21714120
TI  - Brain, the last fortress of sarcoma: similar dismal outcome but discrepancy of
      timing of brain metastasis in bone and soft tissue sarcoma.
AB  - BACKGROUND AND OBJECTIVE: Brain metastasis is a rare but dismal event in
      sarcomas. However, the pattern of occurrence and the prognostic factors
      associated with post-brain metastasis survival (PBMS) are not yet well
      characterized. METHODS: Sarcoma patients treated at one institute within 10-year
      period were retrospectively reviewed and those with brain metastasis were
      identified. The incidence of brain metastasis was demonstrated by case per person
      years and cumulative incidence curves. Univariate factors associated with PBMS
      were analyzed. RESULTS: Among 611 sarcoma patients, 20 (3.3%) developed brain
      metastasis. Alveolar soft part sarcoma (ASPS) and osteosarcoma were the most
      common subtypes. Overall, the cumulative incidence was 3.9% at 5 years and 8.4%
      at 10 years. However, the incidence in STS patients continued to rise up to 10
      years after primary diagnosis, whereas it reached a plateau in bone sarcoma
      patients at 3 years. Median PBMS was 1.67 months. Univariate factors associated
      with better PBMS included ASPS histology, initial surgical treatment, and brain
      irradiation for non-surgically treated patients. CONCLUSION: Our study revealed a
      discrepancy in the timing of occurrence of brain metastasis between STS and bone
      sarcoma. However, patients with brain metastasis had a poor prognosis,
      implicating the brain as the last fortress of sarcoma.

PMID- 21714121
TI  - Cell death-independent functions of granzymes: hit viruses where it hurts.
AB  - Granule exocytosis by cytotoxic lymphocytes is the key mechanism of our immune
      response to eliminate virus-infected cells. These lytic granules contain the pore
      forming protein perforin and a set of five serine proteases called granzymes
      (GrA, GrB, GrH, GrK, GrM) that display distinct substrate specificities.
      Granzymes have mostly been studied for their ability to induce cell death.
      However, viruses have evolved many inhibitors to effectively block apoptosis.
      Evidence is emerging that granzymes also use noncytotoxic strategies to inhibit
      viral replication and potential viral reactivation from latency. Granzymes
      directly cleave viral or host cell proteins that are required in the viral life
      cycle. Furthermore, granzymes induce a pro-inflammatory cytokine response to
      create an antiviral environment. In this review, we summarize and discuss these
      novel strategies by which the immune system counteracts viral infections, and we
      will address the potential therapeutic applications that could emerge from this
      intriguing mechanism.

PMID- 21714122
TI  - Phytosterols can impair vitamin D intestinal absorption in vitro and in mice.
AB  - SCOPE: Adequate vitamin D status is necessary and beneficial for health, although
      deficiency and insufficiency are very common. As cholecalciferol (vitamin D(3) )
      structure is close to cholesterol structure, we hypothesized that phytosterols,
      frequently used to decrease cholesterol, intestinal absorption and consequently
      to reduce hypercholesterolemia, may also interact with cholecalciferol
      absorption. METHODS AND RESULTS: beta-Sitosterol effect on cholecalciferol
      postprandial response was first assessed in mice. We then evaluated the effect of
      different sterols on (i) cholecalciferol micellar incorporation, (ii)
      cholecalciferol apical uptake and (iii) basolateral efflux in vitro or ex vivo.
      In mice, cholecalciferol bioavailability was 15-fold lower in the presence of
      beta-sitosterol (p<0.05). This can partly be explained by the fact that
      phytosterols significantly impaired cholecalciferol incorporation into mixed
      micelles (from -16 to -36% depending on sterol micellar composition). This can
      also be due to the fact that in Caco-2 cells and mouse intestinal explants,
      phytosterols significantly lowered cholecalciferol apical uptake (from -13 to 
      39%). Conversely, phytosterols had no effect on cholecalciferol secretion at the
      basolateral side of Caco-2 cells. CONCLUSION: The present data suggest for the
      first time that phytosterols can interact with vitamin D(3) intestinal
      absorption. This interaction can be explained by a competition for micellar
      incorporation and for apical uptake.

PMID- 21714123
TI  - Oral tolerance induction does not resolve gastrointestinal inflammation in a
      mouse model of food allergy.
AB  - SCOPE: Oral immunotherapy (OIT) involving continuous oral administration of
      allergenic foods has gained attention as a therapy for food allergies. To study
      the influence of oral administration of allergenic foods on gastrointestinal
      symptoms including inflammation, we established a mouse model of food-induced
      intestinal allergy. METHODS AND RESULTS: BALB/c mice were fed an egg white (EW)
      diet containing ovalbumin (OVA, a major EW allergen) after intraperitoneal
      sensitisation with OVA and Alum. The mice on the EW diet for one wk presented
      gastrointestinal symptoms (i.e. weight loss and soft stools) and inflammation in
      the small intestines (i.e. duodenum, jejunum and ileum). Further continuous EW
      diet resolved the weight loss but not the soft stools. Splenic CD4(+) T-cells of
      EW diet-fed mice on the continuous diet showed less proliferation and cytokine
      production compared with those of control mice, suggesting tolerance induction by
      the diet. The continuous EW diet reduced levels of OVA-specific IgE antibodies,
      but significantly aggravated the inflammation in the jejunum. CONCLUSION: Our
      mouse model would be useful to investigate inflammatory and regulatory mechanisms
      in food-induced intestinal allergies. Our results suggest potential
      gastrointestinal inflammation in patients undergoing OIT as continuous
      administration of allergenic foods, even though the therapy may induce clinical
      tolerance.

PMID- 21714124
TI  - Enhancing the bioavailability of resveratrol by combining it with piperine.
AB  - SCOPE: Resveratrol (3,5,4'-trihydroxystilbene) is a phytoalexin shown to possess
      a multitude of health-promoting properties in pre-clinical studies. However, the
      poor in vivo bioavailability of resveratrol due to its rapid metabolism is being
      considered as a major obstacle in translating its effects in humans. In this
      study, we examined the hypothesis that piperine will enhance the pharmacokinetic
      parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its
      elimination. METHODS AND RESULTS: Employing a standardized LC/MS assay, we
      determined the effect of piperine co-administration with resveratrol on serum
      levels resveratrol and resveratrol-3-O-beta-D-glucuronide in C57BL mice. Mice
      were administered resveratrol (100 mg/kg; oral gavage) or resveratrol (100 mg/kg;
      oral gavage)+piperine (10 mg/kg; oral gavage), and the serum levels of
      resveratrol and resveratrol-3-O-beta-D-glucuronide were analyzed at different
      times. We found that the degree of exposure (i.e. AUC) to resveratrol was
      enhanced to 229% and the maximum serum concentration (C(max)) was increased to
      1544% with the addition of piperine. CONCLUSION: Our study demonstrated that
      piperine significantly improves the in vivo bioavailability of resveratrol.
      However, further detailed research is needed to study the mechanism of improved
      bioavailability of resveratrol via its combination with piperine as well as its
      effect on resveratrol metabolism.

PMID- 21714125
TI  - Emotional perception in patients with eating disorders in comparison with
      depressed patients.
AB  - OBJECTIVE: Emotion regulation is a key issue for many psychiatric and
      psychosomatic disorders, including eating disorders. Eating disordered patients
      (EDP) show high levels of depressive comorbidity, and there is much uncertainty
      about disorder-specific deficits. This study is aimed at delineating disorder
      specific disturbances of emotional perception in EDP. METHOD: Fifty-two EDP were
      compared with 35 depressed patients (DP) and 25 healthy controls. They rated
      their emotional experience when viewing visual emotional stimuli. Emphasis was
      placed on the patients' perception of their own emotions and not on the
      recognition of emotions in others. Severity of depression was assessed by the
      Beck Depression Inventory. RESULTS: Eating disordered patients and DP reported
      less anger than healthy controls-independent of the severity of depression. In
      addition, DP showed increased levels of disgust when confronted with anger
      stimuli. Happiness was rated less in EDP and DP, which was associated with
      severity of depression. There were no differences between the EDP subgroups
      bulimia nervosa and anorexia nervosa. CONCLUSION: Eating disordered patients and
      DP showed alterations of emotional perception of anger, an emotion which is
      closely linked to interpersonal difficulties. Alterations in emotional perception
      of EDP and DP might be due to more general emotion regulation disturbances. In
      order to detect more subtle differences between psychiatric subgroups, more
      sophisticated investigation tools are needed. Increased disgust ratings in DP
      merit further investigation.

PMID- 21714126
TI  - Resveratrol derivatives as promising chemopreventive agents with improved potency
      and selectivity.
AB  - SCOPE: Despite scores of investigations, the actual impact of resveratrol (3,5,4'
      trihydroxy-trans-stilbene) on human health, as a dietary component or supplement,
      remains moot. This is due to many factors, such as relatively low potency,
      pleiotropic mechanisms, and rapid metabolism. Nonetheless, as a promiscuous
      molecule that interacts with numerous targets, resveratrol can be viewed as a
      scaffold for designing structural relatives potentially capable of mediating more
      intense responses with greater mechanistic stringency. METHODS AND RESULTS: We
      currently report the synthesis and biological evaluation of 92 stilbene analogs.
      The compounds were tested with in vitro assays for activation of quinone
      reductase 1, inhibition of quinone reductase 2, nitric oxide production,
      aromatase, NFkappaB, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine
      decarboxylase, or cyclooxygenase-1 and -2, quenching of 2,2-diphenyl-1
      picrylhydrazyl free radical, interaction with estrogen receptors, and as
      antiproliferative agents. Several compounds were found to mediate responses with
      much greater potency than resveratrol; some mediated pleiotropic responses, as is
      the case with the parent molecule, but others were highly specific or totally
      inactive. When administered to rats, higher serum concentrations and greater
      stability was demonstrated with prototype lead molecules. CONCLUSION: Owing to
      structural simplicity, facile syntheses are available for large-scale production.
      These data support the promise of more advanced development of novel resveratrol
      derivatives as drug entities.

PMID- 21714127
TI  - Resveratrol and prostate cancer: promising role for microRNAs.
AB  - SCOPE: Resveratrol (Res) has anticancer activity in prostate cancer (PCa), which
      can be attributed to modulation of microRNAs (miRNAs/miRs). miRNAs/miRs are small
      non-coding RNAs that negatively regulate gene expression. We have analyzed
      differential miRNA expression in PCa cells treated with Res. METHODS AND RESULTS:
      Using miRNA microarrays we found that 23 miRNAs were significantly down-regulated
      and 28 miRNAs were significantly up-regulated after Res treatment. The down
      regulated miRs included miR-17-92 and miR-106ab clusters with well recognized
      oncogenic properties while the up-regulated miRs included several tumor
      suppressors. Selected miRs were verified by qRT-PCR, including miR-17, miR-20a,
      miR-20b, miR-106a and miR106b. Since these miRNAs target PTEN (phosphatase and
      tensin homolog deleted on chromosome 10), we performed Western blot to confirm up
      regulation of PTEN in PCa cells. In addition, using TargetScan database, we have
      identified putative mRNA targets for Res-induced down- and up-regulated miRs.
      Using a bioinformatics approach, we generated gene networks specifically altered
      by Res-regulated miRNAs. CONCLUSION: Our results indicate that the dietary
      compound Res may play an important role in prostate carcinogenesis through
      modulation of miRNA expression: Res down-regulated oncogenic miRs and up
      regulated tumor suppressor miRs in PCa cells. Further in-depth studies are
      necessary in order to fully recognize the beneficial miRNA-mediated effects of
      Res in PCa.

PMID- 21714128
TI  - Acrolein induced DNA damage, mutagenicity and effect on DNA repair.
AB  - Acrolein (Acr) is a ubiquitous environmental contaminant; it also can be
      generated endogenously by lipid peroxidation. Acr contains a carbonyl group and
      an olefinic double bond; it can react with many cellular molecules including
      amino acids, proteins and nucleic acids. In this review article we focus on
      updating information regarding: (i) Acr-induced DNA damage and methods of
      detection, (ii) repair of Acr-DNA damage, (iii) mutagenicity of Acr-DNA adducts,
      (iv) sequence specificity and methylation effect on Acr-DNA adduct formation and
      (v) the role of Acr in human cancer. We have found that Acr can inhibit DNA
      repair and induces mutagenic Acr-dG adducts and that the binding spectrum of Acr
      in the p53 gene in normal human bronchial epithelial cells is similar to the p53
      mutational spectrum in lung cancer. Since Acr-DNA adduct has been identified in
      human lung tissue and Acr causes bladder cancer in human and rat models, we
      conclude that Acr is a major lung and bladder carcinogen, and its carcinogenicity
      arises via induction of DNA damage and inhibition of DNA repair.

PMID- 21714129
TI  - Acrolein scavengers: reactivity, mechanism and impact on health.
AB  - Acrolein (ACR) is an alpha,beta-unsaturated aldehyde that exists extensively in
      the environment and (thermally processed) foods. It can also be generated through
      endogenous metabolism. Its high electrophilicity makes this aldehyde notorious
      for its facile reaction with biological nucleophiles, leading to the modification
      of proteins/DNA and depletion of glutathione. Recent studies also have revealed
      its roles in disturbing various cell signing pathways in biological systems. With
      growing evidences of ACR's implication in human diseases, strategies to eliminate
      its hazardous impacts are of great importance. One of the intervention strategies
      is the application of reactive scavengers to directly trap ACR. Some known ACR
      scavengers include sulfur (thiol)-containing and nitrogen (amino)-containing
      compounds as well as the newly emerging natural polyphenols. In this review, the
      interactions between ACR and its scavengers are highlighted. The discussion about
      ACR scavengers is mainly focused on their chemical reactivity, trapping
      mechanisms as well as their roles extended to biological relevance. In addition
      to their direct trapping effect on ACR, these scavengers might possess multiple
      functions and offer additional benefits against ACR-induced toxicity. A
      comprehensive understanding of the mechanism involved may help to establish ACR
      scavenging as a novel therapeutic intervention against human diseases that are
      associated with ACR and/or oxidative stress.

PMID- 21714130
TI  - Optimal pairwise alignment of fixed protein structures in subquadratic time.
AB  - The problem of finding an optimal structural alignment for a pair of superimposed
      proteins is often amenable to the Smith-Waterman dynamic programming algorithm,
      which runs in time proportional to the product of lengths of the sequences being
      aligned. While the quadratic running time is acceptable for computing a single
      alignment of two fixed protein structures, the time complexity becomes a
      bottleneck when running the Smith-Waterman routine multiple times in order to
      find a globally optimal superposition and alignment of the input proteins. We
      present a subquadratic running time algorithm capable of computing an alignment
      that optimizes one of the most widely used measures of protein structure
      similarity, defined as the number of pairs of residues in two proteins that can
      be superimposed under a predefined distance cutoff. The algorithm presented in
      this article can be used to significantly improve the speed-accuracy tradeoff in
      a number of popular protein structure alignment methods.

PMID- 21714131
TI  - In search of the protein native state with a probabilistic sampling approach.
AB  - The three-dimensional structure of a protein is a key determinant of its
      biological function. Given the cost and time required to acquire this structure
      through experimental means, computational models are necessary to complement wet
      lab efforts. Many computational techniques exist for navigating the high
      dimensional protein conformational search space, which is explored for low-energy
      conformations that comprise a protein's native states. This work proposes two
      strategies to enhance the sampling of conformations near the native state. An
      enhanced fragment library with greater structural diversity is used to expand the
      search space in the context of fragment-based assembly. To manage the increased
      complexity of the search space, only a representative subset of the sampled
      conformations is retained to further guide the search towards the native state.
      Our results make the case that these two strategies greatly enhance the sampling
      of the conformational space near the native state. A detailed comparative
      analysis shows that our approach performs as well as state-of-the-art ab initio
      structure prediction protocols.

PMID- 21714132
TI  - A two-stage evolutionary approach for effective classification of hypersensitive
      DNA sequences.
AB  - Hypersensitive (HS) sites in genomic sequences are reliable markers of DNA
      regulatory regions that control gene expression. Annotation of regulatory regions
      is important in understanding phenotypical differences among cells and diseases
      linked to pathologies in protein expression. Several computational techniques are
      devoted to mapping out regulatory regions in DNA by initially identifying HS
      sequences. Statistical learning techniques like Support Vector Machines (SVM),
      for instance, are employed to classify DNA sequences as HS or non-HS. This paper
      proposes a method to automate the basic steps in designing an SVM that improves
      the accuracy of such classification. The method proceeds in two stages and makes
      use of evolutionary algorithms. An evolutionary algorithm first designs optimal
      sequence motifs to associate explicit discriminating feature vectors with input
      DNA sequences. A second evolutionary algorithm then designs SVM kernel functions
      and parameters that optimally separate the HS and non-HS classes. Results show
      that this two-stage method significantly improves SVM classification accuracy.
      The method promises to be generally useful in automating the analysis of
      biological sequences, and we post its source code on our website.

PMID- 21714133
TI  - Ranking valid topologies of the secondary structure elements using a constraint
      graph.
AB  - Electron cryo-microscopy is a fast advancing biophysical technique to derive
      three-dimensional structures of large protein complexes. Using this technique,
      many density maps have been generated at intermediate resolution such as 6-10 A
      resolution. Although it is challenging to derive the backbone of the protein
      directly from such density maps, secondary structure elements such as helices and
      beta-sheets can be computationally detected. Our work in this paper provides an
      approach to enumerate the top-ranked possible topologies instead of enumerating
      the entire population of the topologies. This approach is particularly practical
      for large proteins. We developed a directed weighted graph, the topology graph,
      to represent the secondary structure assignment problem. We prove that the
      problem of finding the valid topology with the minimum cost is NP hard. We
      developed an O(N(2)2(N)) dynamic programming algorithm to identify the topology
      with the minimum cost. The test of 15 proteins suggests that our dynamic
      programming approach is feasible to work with proteins of much larger size than
      we could before. The largest protein in the test contains 18 helical sticks
      detected from the density map out of 33 helices in the protein.

PMID- 21714134
TI  - A method for the detection of meaningful and reproducible group signatures from
      gene expression profiles.
AB  - Gene expression microarrays are commonly used to detect the biological signature
      of a disease or to gain a better understanding of the underlying mechanism of how
      a group of drugs treat a specific disease. The outcome of such experiments, e.g.
      the signature, is a list of differentially expressed genes. Reproducibility
      across independent experiments remains a challenge. We are interested in creating
      a method that can detect the shared signature of a group of expression profiles,
      e.g. a group of samples from individuals with the same disease or a group of
      drugs that treat the same therapeutic indication. We have developed a novel
      Weighted Influence-Rank of Ranks (WIMRR) method, and we demonstrate its ability
      to produce both meaningful and reproducible group signatures.

PMID- 21714135
TI  - Changes of circulatory-metabolic indices and skull biomechanics with brain
      activity during aging.
AB  - The cerebral blood flow values used in experimental and clinical investigations
      as the informative criteria for brain blood supply are often misleading. The
      correlation between the cerebral blood supply and brain function is not proven in
      all cases. An increase of brain activity is known to be accompanied by a rise of
      blood flow in activated regions, while a decreased activity results in a
      decreased blood flow. This demonstrates the close correlation between the brain
      blood supply and its activity. Such a correlation had not been noted in the age
      dependent decrease of cerebral blood flow, suggesting the existence of special
      age-related mechanisms that develop with age to maintain brain metabolism. The
      biomechanical properties are of special significance as predicted in the early
      20th century. Only recently were they validated by the simultaneous recording of
      Transcranial Dopplerogram and Rheoencephalogram with in-depth analysis focused on
      single cardiac cycles. Functioning of the intracranial blood and cerebrospinal
      fluid dynamics was integrated with a special physiological test "Prognosis-2" to
      measure brain cognitive function. Correlation was demonstrated with the
      circulatory-metabolic state of brain activity, especially in people with changing
      cognitive function. The data supports a conceptual model of adequate circulatory
      metabolic supply of brain activity, showing the functional unity, which follows
      from integration of the mentioned systems.

PMID- 21714136
TI  - Central N-acetylcysteine effects on baroreflex in juvenile spontaneously
      hypertensive rats.
AB  - In this study, we evaluated the acute effects of central NAC administration on
      baroreflex in juvenile SHR and Wistar Kyoto (WKY) rats. Male SHR and WKY rats (8
      10 weeks old) were implanted with a stainless steel guide cannula into the fourth
      cerebral ventricle (4th V). The femoral artery and vein were cannulated for mean
      arterial pressure (MAP) and heart rate (HR) measurement and drug infusion,
      respectively. After basal MAP and HR recordings, the baroreflex was tested with a
      pressor dose of phenylephrine (PHE, 8 MUg/kg, bolus) and a depressor dose of
      sodium nitroprusside (SNP, 50 MUg/kg, bolus). Baroreflex was evaluated before, 5,
      15, 30 and 60 minutes after NAC injection into the 4th V. Vehicle treatment did
      not change baroreflex responses in WKY and SHR. Central NAC slightly but
      significantly increased basal HR at 15 minutes and significantly reduced PHE
      induced increase in MAP 30 and 60 minutes after NAC injection (p < 0.05) in WKY
      rats. In relation to SHR, NAC decreased HR range 15 and 30 minutes after its
      administration. In conclusion, acute NAC into the 4th V does not improve
      baroreflex in juvenile SHR.

PMID- 21714137
TI  - Does the stability of elbow support influence the elbow joint matching accuracy?
AB  - The aim of the present work was to determine if the elbow joint instability and
      translatory movements during elbow flexion lead to significant errors in elbow
      angle perception. The matching elbow was fixed on a rocking platform of two
      different heights so that the elbow flexion was associated with tilting movement
      of the support and the angle/torque relationship changed depending on the height
      of the platform. The matching on any of the rocking supports did not cause an
      over-flexion constant error but it did increase the error variance, especially in
      the high rocking support condition. An adaptation to the rocking support
      condition was revealed by an after-effect resulting in an overestimation of the
      reference angle in the final testing on a rigid support. It is concluded that the
      elbow angle perception is modified as a result of adaptation to the rocking
      support, which is associated with recalibration of position sense during the
      experimental session. The results are consistent with the hypothesis that the
      estimation of the elbow joint angle depends on the internal representation of the
      arm's dynamics.

PMID- 21714138
TI  - Effects of wi-fi signals on the p300 component of event-related potentials during
      an auditory hayling task.
AB  - The P300 component of event-related potentials (ERPs) is believed to index
      attention and working memory (WM) operation of the brain. The present study
      focused on the possible gender-related effects of Wi-Fi (Wireless Fidelity)
      electromagnetic fields (EMF) on these processes. Fifteen male and fifteen female
      subjects, matched for age and education level, were investigated while performing
      a modified version of the Hayling Sentence Completion test adjusted to induce WM.
      ERPs were recorded at 30 scalp electrodes, both without and with the exposure to
      a Wi-Fi signal. P300 amplitude values at 18 electrodes were found to be
      significantly lower in the response inhibition condition than in the response
      initiation and baseline conditions. Independent of the above effect, within the
      response inhibition condition there was also a significant gender X radiation
      interaction effect manifested at 15 leads by decreased P300 amplitudes of males
      in comparison to female subjects only at the presence of EMF. In conclusion, the
      present findings suggest that Wi-Fi exposure may exert gender-related alterations
      on neural activity associated with the amount of attentional resources engaged
      during a linguistic test adjusted to induce WM.

PMID- 21714139
TI  - On the relationship between human sensorimotor adaptability and event-related
      potentials.
AB  - It was explored if the speed with which an individual learns to deal with new
      environments and challenges can be predicted on the basis of his/her brain's
      response to irrelevant (repeating) and novel auditory stimuli. In this study, 26
      subjects threw 30 light-weight balls at a target with and without vision
      distorting goggles. The horizontal displacement from a bull's-eye target was
      measured and the rate and degree of adaptation were computed. The adaptation
      parameters were correlated with evoked and event-related potential (EP/ERP)
      measures of the subject's ability to suppress irrelevant information and respond
      to novel stimuli. Only a weak (or a trend to) correlation was found between the
      behavioral adaptation and some of the EP/ERP measures. The correlations were
      limited to EP parameters in the 100 to 200 ms post-stimulus range reflecting the
      ability to suppress irrelevant information. Thus we conclude that the speed with
      which an individual adapts to a new environment is at best weakly correlated with
      brain activity associated with stimulus memory and classification.

PMID- 21714140
TI  - Constructing brain functional networks from EEG: partial and unpartial
      correlations.
AB  - We consider electroencephalograms (EEGs) of healthy individuals and compare the
      properties of the brain functional networks found through two methods:
      unpartialized and partialized cross-correlations. The networks obtained by
      partial correlations are fundamentally different from those constructed through
      unpartial correlations in terms of graph metrics. In particular, they have
      completely different connection efficiency, clustering coefficient,
      assortativity, degree variability, and synchronization properties. Unpartial
      correlations are simple to compute and they can be easily applied to large-scale
      systems, yet they cannot prevent the prediction of non-direct edges. In contrast,
      partial correlations, which are often expensive to compute, reduce predicting
      such edges. We suggest combining these alternative methods in order to have
      complementary information on brain functional networks.

PMID- 21714141
TI  - Ask the doctor.  Is it true that we use only 10% of our brains?

PMID- 21714142
TI  - I'm having trouble sleeping.  Would a sleep study help?

PMID- 21714143
TI  - [Fireworks fear].

PMID- 21714144
TI  - Evidence that "brain-specific" FOX-1, FOX-2, and nPTB alternatively spliced
      isoforms are produced in the lens.
AB  - PURPOSE: Alternative RNA splicing is essential in development and more rapid
      physiological processes that include disease mechanisms. Studies over the last 20
      years demonstrated that RNA binding protein families, which mediate the
      alternative splicing of a large percentage of genes in mammals, contain isoforms
      with mutually exclusive expression in non-neural and neural progenitor cells vs.
      post-mitotic neurons, and regulate the comprehensive reprogramming of alternative
      splicing during neurogenesis. Polypyrimidine tract binding (PTB) proteins and Fox
      1 proteins also undergo mutually exclusive alternative splicing in neural and non
      neural cells that regulates their tissue-specific expression and splicing
      activities. Over the past 50 years, striking morphological similarities noted
      between lens fiber cells and neurons suggested that cell biology processes and
      gene expression profiles may be shared as well. Here, we examined mouse and rat
      lenses to determine if alternative splicing of neuronal nPTB and Fox-1/Fox-2
      isoforms also occurs in lenses. METHODS: Immunoblot, immunofluorescence, and RT
      PCR were used to examine expression and alternative splicing of transcripts in
      lens and brain. RESULTS: We demonstrated that exon 10 is predominantly included
      in nPTB transcripts consistent with nPTB protein in lenses, and that
      alternatively spliced Fox-1/-2 lens transcripts contain exons that have been
      considered neuron-specific. We identified a 3' alternative Fox-1 exon in lenses
      that encodes a nuclear localization signal consistent with its protein
      distribution detected in fiber cells. Neuronal alternative splicing of kinesin
      KIF1Bbeta2 has been associated with PTB/nPTB and Fox-2, and we found that two
      'neuron-specific' exons are also included in lenses. CONCLUSIONS: The present
      study provides evidence that alternative neuronal nPTB and Fox-1/Fox-2 isoforms
      are also produced in lenses. These findings raise questions regarding the extent
      these factors contribute to a similar reprogramming of alternative splicing
      during lens differentiation, and the degree that alternative gene transcripts
      produced during neurogenesis are also expressed in the lens.

PMID- 21714145
TI  - International disease monitoring, January to March 2011.

PMID- 21714146
TI  - A small regulatory core that discriminates the gene expression profiles of cancer
      points to a 'Medusa' structure of the genomic network.

PMID- 21714147
TI  - On immunologists and microbiologists: ground zero in the battle for
      interdisciplinary knowledge.
AB  - The individual disciplines of microbiology and immunology are exploding with new
      information necessary for understanding host-pathogen relationships, infectious
      diseases, cancer, and autoimmunity. Because of overlapping scientific interests,
      immunologists and microbiologists often share common academic affiliations. The
      coexistence is uneasy. Significant problems arise because the groups have evolved
      different intellectual traditions. Pressures are intensified by sporadic changes
      in perceptions of their relative worth. As the mixing of microbiologists and
      immunologists can be likened to ground zero in the fight for interdisciplinary
      knowledge, it is useful, at this time of escalating data acquisition and growing
      appreciation for multidisciplinary research, to examine their histories, the
      challenges to amalgamation, and the advantages of their association for the
      advancement of knowledge and the delivery of protection against disease. The
      exploration supports a recommitment to integration of the disciplines and a
      proposal to facilitate this by inclusion of expertise bridging the areas.

PMID- 21714148
TI  - Chest X-ray quiz.

PMID- 21714149
TI  - [Not Available].

PMID- 21714150
TI  - [Not Available].

PMID- 21714151
TI  - [Not Available].

PMID- 21714152
TI  - [When retirement arrives].

PMID- 21714153
TI  - Abstracts of the British Association of Urological Surgeons 2011 Annual
      Scientific Meeting. Liverpool, United Kingdom. June 20-23, 2011.

PMID- 21714154
TI  - Abstracts of the 7th European Association of Dermato-Oncology (EADO) Congress.
      June 20-23, 2011. Nantes, France.

PMID- 21714155
TI  - Abstracts of the 8th European Cytogenetics Conference. July 2-5, 2011. Porto,
      Portugal.

PMID- 21714156
TI  - Abstracts of the 2011 Tripartite Colorectal Meeting held in conjunction with the
      Australian Association of Stomal Therapy Nurses Conference. July  3-7, 2011.
      Cairns, Australia.

PMID- 21714157
TI  - Proceedings of the 11th International Conference on Malignant Lymphoma, 15-18
      June 2011, Lugano, Switzerland.

PMID- 21714158
TI  - The Eighth Australian Peptide Conference: peptides--tools, targets and
      therapeutics.

PMID- 21714159
TI  - Pickled cabbage.

PMID- 21714160
TI  - Magical dinners: an immigrant Thanksgiving.

PMID- 21714161
TI  - Patients and solipsism: the psychology of decision making for prostate cancer
      treatment.

PMID- 21714162
TI  - Should decision models drive the decision for prostate biopsy?

PMID- 21714163
TI  - GAVI funding meeting exceeds expectations.

PMID- 21714164
TI  - South Sudan faces grim health and humanitarian situation.

PMID- 21714165
TI  - Why are the mentally ill still bearing arms?.

PMID- 21714166
TI  - The IOC's endeavour to protect the health of the athlete continues.

PMID- 21714167
TI  - Reflections: neurology and the humanities. Buster's view.

PMID- 21714168
TI  - The plant cell cycle.

PMID- 21714169
TI  - [Pathogenesis of septic wounds].

PMID- 21714170
TI  - Respiration.

PMID- 21714171
TI  - Life in the colonies: learning the alien ways of colonial organisms.
AB  - Who needs to go to outer space to study alien beings when the oceans of our own
      planet abound with bizarre and unknown creatures? Many of them belong to sessile
      clonal and colonial groups, including sponges, hydroids, corals, octocorals,
      ascidians, bryozoans, and some polychaetes. Their life histories, in many ways
      unlike our own, are a challenge for biologists. Studying their ecology, behavior,
      and taxonomy means trying to "think like a colony" to understand the factors
      important in their lives. Until the 1980s, most marine ecologists ignored these
      difficult modular organisms. Plant ecologists showed them ways to deal with the
      two levels of asexually produced modules and genetic individuals, leading to a
      surge in research on the ecology of clonal and colonial marine invertebrates.
      Bryozoans make excellent model colonial animals. Their life histories range from
      ephemeral to perennial. Aspects of their lives such as growth, reproduction,
      partial mortality due to predation or fouling, and the behavior of both
      autozooids and polymorphs can be studied at the level of the colony, as well as
      that of the individual module, in living colonies and over time.

PMID- 21714172
TI  - Findings of misconduct in science/research misconduct.

PMID- 21714173
TI  - Last gasp for Primatene Mist?

PMID- 21714174
TI  - I've been seeing tiny, random black specks in front of my eyes. Could this be
      some kind of eye disease, like macular degeneration?

PMID- 21714175
TI  - How can we retain muscle strength as we grow older?

PMID- 21714176
TI  - [Paleopathology of violent injuries, before the discovery of gunpowder].

PMID- 21714177
TI  - Peer play, emotion understanding, and socio-moral explanation: the role of
      gender.
AB  - Engagement in peer play is an important factor in young children's adjustment as
      they make the transition to school. We evaluated individual differences in peer
      play within a sample of 58 children aged 4-5 years. Among boys, but not among
      girls, emotion understanding and verbal ability independently served as positive
      predictors of interactive peer play and negative predictors of disconnected play.
      Among girls, but not among boys, interactive peer play and socio-moral reasoning
      about peer conflict situations independently predicted sociometric most-like
      nominations. The results provide a foundation for further research on divergence
      in the early peer play of girls and boys.

PMID- 21714178
TI  - Validity of clinical diagnosis in dermatology.
AB  - OBJECTIVE: We evaluated the accuracy of the clinical diagnostic process performed
      by dermatologists. MATERIAL AND METHODS: We conducted a cross-sectional study,
      based on a retrospective search of data at a dermatology outpatient department.
      Fifteen skin diseases were selected. A group of patients with those diseases at
      their first outpatient visit and a further histopathological study were included.
      The accuracy of any given clinical diagnosis was studied taking the
      histopathological diagnosis as the gold standard. Validity indices were
      calculated. RESULTS: We studied 2188 patients. Skin diseases were more prevalent
      among women (p < 0.05). While the clinical diagnostic process displayed a high
      level of validity in melanocytic naevi and basal cell carcinoma, a poor level was
      nevertheless observed for Bowen's disease (sensitivity 22.8%, specificity 96.5%).
      The most frequent sites of appearance of dermatological problems were face and
      trunk. CONCLUSIONS: Evaluation of diagnosis in pathologies having an available
      "gold standard" enables the accuracy of clinical diagnoses to be verified. The
      validity of clinical diagnosis was high.

PMID- 21714179
TI  - Does orthopaedics need randomized controlled trials?

PMID- 21714180
TI  - Health-care technology: Industrial and clinical applications.

PMID- 21714181
TI  - [Abstracts of the 23rd Annual Meeting of the Association for Rapid Method and
      Automation in Microbiology. June 26, 2010. Gifu, Japan].

PMID- 21714182
TI  - Complex pigment evolution in the Caryophyllales.
AB  - Carotenoids and flavonoids including anthocyanins are the predominant pigments in
      flowering plants, where they play important roles in pollination, seed dispersal,
      protection against stress and signalling. In certain families within the
      Pentapetalae order Caryophyllales, an unusual class of pigments, known as
      betalains, replaces the more common anthocyanins. This isolated occurrence of
      betalains in the Caryophyllales has stimulated over half a century of debate and
      experimentation. Numerous hypotheses have been suggested to explain the
      phylogenetically restricted occurrence of betalains and their apparent mutual
      exclusion with anthocyanins. In this review, we evaluate these hypotheses in the
      face of a changing interpretation of Caryophyllales phylogeny and new comparative
      genetic data. Phylogenetic analyses expose substantial gaps in our knowledge of
      the early evolution of pigments in the Caryophyllales and suggest pigmentation to
      be much more labile than previously recognized. Reconstructions of character
      evolution imply multiple switches from betalain to anthocyanin pigmentation, but
      also allow for possible multiple origins of betalains. Comparative genetic
      studies propose possible mechanisms underlying switches between pigment types and
      suggest that transcriptional down-regulation of late-acting enzymes is
      responsible for a loss of anthocyanins. Given these insights from molecular
      phylogenetics and comparative genetics, we discuss outstanding questions and
      define key goals for future research.

PMID- 21714183
TI  - Patterns of activities of root phosphomonoesterase and  phosphodiesterase in
      wetland plants as a function of  macrophyte species and ambient phosphorus
      regime.
AB  - Phosphorus (P)-limited plants produce higher amounts of root phosphatases, but
      research has mostly focused on phosphomonoesterases (PMEs). Because phosphate
      diesters can form a significant proportion of organic P in wetlands, we aimed to
      determine whether wetland plants produce both root PMEs and root
      phosphodiesterases (PDEs), and, if so, what factors influence activities of these
      enzymes. We measured the activities of root PMEs and PDEs colorimetrically in a
      wide range of macrophytes from natural and P-enriched wetlands. Hydrolyzable P in
      sediments was analyzed using commercially available PMEs and PDEs. In all
      species, both root PMEs and PDEs were always present, and their activities were
      closely correlated. Sedges and broadleaved emergents had the highest activity of
      both enzymes, while those of floating-leaved plants were the lowest. Redundancy
      analysis revealed close association between root enzymes and the proportion of
      monoesterase- and diesterase-hydrolyzable dissolved unreactive P. Both enzymes
      were positively correlated with root tissue N : P ratio. Both plant and sediment
      traits were important when explaining differences in enzyme activities. Although
      the activities are related to ambient P regime, the relationship was not close
      enough to use root enzymes as reliable predictors of dissolved unreactive P that
      is hydrolyzed by sediment phosphomono- and diesterases.

PMID- 21714184
TI  - Competition. Are you looking at my patients.

PMID- 21714185
TI  - Workforce. Practice managers' big moment.

PMID- 21714186
TI  - GPs 'must not rebuild past'.

PMID- 21714187
TI  - A new era of commissiong. So how will it work?

PMID- 21714188
TI  - Efficiency. It means nothing to me....

PMID- 21714189
TI  - Hell no, we won't ACO. Providers, once eager to sign up for new program, say
      proposed rule on accountable care is a deal-breaker.
AB  - Hospital executives were eager to sign up for Medicare's proposed ACO program-
      until they saw the proposed rule spelling out how the CMS wants to structure it.
      They see too many risks, with too little chance of rewards. Stephen Mansfield,
      left, of Methodist Health System, describes the rule as "cold water" on the
      industry's interest and says he fears a promising opportunity will be sidelined.
      "I am so disappointed," Mansfield says.

PMID- 21714190
TI  - Not everyone's a fan. Geographic pay report creates provider schism.

PMID- 21714191
TI  - Unanswered questions. Hospitals seeking more guidance on HAC rule.

PMID- 21714192
TI  - Taken to the top. Feds side against providers in Medicaid dispute.

PMID- 21714193
TI  - Robust blood market. FTC attaches strings to merger, but competition concerns
      remain.

PMID- 21714194
TI  - Fiduciary failure. Lifespan violated duty to one of its hospitals: judge.

PMID- 21714195
TI  - A solid year. Annual survey shows health systems posted strong revenue and
      earnings, but expenses are also rising.

PMID- 21714196
TI  - Largest healthcare fraud settlements. Ranked by settlement amount recovered under
      the False Claims Act in 2010.

PMID- 21714197
TI  - Persistence of high fertility in tropical Africa: the case of the Democratic
      Republic of the Congo.
AB  - The article explores how geography, history, and society have shaped childbearing
      behaviors over the last half-century, and how they are now being reshaped by
      modernity and the exigencies of urban life, in the democratic Republic of the
      Congo. The decline of prolonged postpartum abstinence and involuntary
      childlessness initially raised fertility to high levels (6-7 children per woman).
      More recently, socioeconomic differentials in fertility have emerged, suggesting
      that the country may be entering a phase of fertility decline. A full-blown
      transition, however, seems still a remote prospect. Supported both by cultural
      traditions and by economic rationality, Congo's people remain largely convinced
      of the benefits of many children for their own and their kin's security. While an
      eventual fertility transition may be taken for granted, the article examines the
      many hurdles, contradictions, and tensions that will have to be overcome to
      achieve that outcome.

PMID- 21714198
TI  - A global perspective on happiness and fertility.
AB  - The literature on fertility and happiness has neglected comparative analysis. We
      investigate the fertility/happiness association using data from the world values
      surveys for 86 countries. We find that, globally, happiness decreases with the
      number of children. This association, however, is strongly modified by individual
      and contextual factors. Most importantly, we find that the association between
      happiness and fertility evolves from negative to neutral to positive above age
      40, and is strongest among those who are likely to benefit most from upward
      intergenerational transfers. In addition, analyses by welfare regime show that
      the negative fertility/ happiness association for younger adults is weakest in
      countries with high public support for families, and the positive association
      above age 40 is strongest in countries where old-age support depends mostly on
      the family. Overall these results suggest that children are a long-term
      investment in well-being, and highlight the importance of the life-cycle stage
      and contextual factors in explaining the happiness/fertility association.

PMID- 21714199
TI  - Family policies in OECD countries: a comparative analysis.
AB  - This article discusses the diversity of family policy models in 28 OECD countries
      in terms of the balance between their different objectives and the mix of
      instruments adopted to implement the policies. Cross-country policy differences
      are investigated by applying a principal component analysis to comprehensive
      country-level data from the OECD Family database covering variables such as
      parental leave conditions, childcare service provision, and financial support to
      families. The results find persistent differences in the family policy patterns
      embedded in different contexts of work-family "outcomes." Country classifications
      of family policy packages only partially corroborate categorizations in earlier
      studies, owing to considerable within-group heterogeneity and the presence of
      group outliers. The Nordic countries outdistance the others with comprehensive
      support to working parents with very young children. Anglo-Saxon countries
      provide much less support for working parents with very young children, and
      financial support is targeted on low-income and large families and focuses on
      preschool and early elementary education. Continental and Eastern European
      countries form a more heterogeneous group, while the support received by families
      in Southern Europe and in Asian countries is much lower in all its dimensions.

PMID- 21714200
TI  - Sport in the trenches: the new deal for masculinity in France.
AB  - During the First World War, the life of a soldier was not just reduced to the
      trenches. In daily military life behind the lines, soldiers had recreational
      activities, some of which were seen as a test of virility, such as visiting
      brothels, and also, as we want to show in this paper, sport practices. For most
      of the French citizen-soldiers, who were working class and mainly from the
      countryside, the contact with allied soldiers has to be understood as a
      significant step in the social construction of gender. Educated in gymnastics,
      shooting and military exercises, French infantrymen (Poilus) and civilians saw
      allied sports and soldier-sportsmen as models of a modern masculinity. In a
      descriptive study of the development of football in the French army, our article
      tries to demonstrate firstly, that football learnt in the army by workers and the
      French rural society extended the influence of sport and its part in the
      construction of masculinity in France. Secondly, we show that the official
      recognition of sport in 1917 by the French army led to the definition of a modern
      French masculinity and to the recognition of the sportsmen-soldier as the model
      of hegemonic masculinity.

PMID- 21714201
TI  - American Sammys and French Poilus in the Great War: sport, masculinities and
      vulnerability.
AB  - The violence and duration of fighting throughout the Great War created an intense
      feeling of vulnerability among the men engaged in battle, which challenged their
      perception of manliness. When the Americans joined the war in 1917, the balance
      between the two opposing armies was modified and the psychological crises of
      French soldiers brought to an end. The confidence shown by the American soldiers
      and their first successes on the battlefield changed the way the French Poilus
      perceived their new allies. From scepticism to admiration, Frenchmen's feelings
      extended beyond the fighting. Indeed, by living with American soldiers in the
      trenches and camps behind the front, French soldiers discovered a new culture
      where games and sport played a major role and contributed to building manliness.
      The Foyers Franco-Americains du Soldat (Franco-American hostels for soldiers)
      provided an ideal place for the cultural transfer of a model of masculinity from
      Sammys to Poilus. The foyers were managed by the American YMCA and eventually
      reached the number of 1,500 in France during the war. These hostels afforded
      soldiers numerous opportunities to develop cultural and sports practices, by
      bringing together Americans and Frenchmen. Mainly based on the archives of the
      American Expeditionary Forces, the YMCA and the French Army, the paper argues
      that the Foyers du Soldat brought to light a new model of masculinity based on
      sport, which challenged the Frenchmen's vision. It aims to show the rapid
      transformation of masculine identity within a context of extreme vulnerability
      and confirms the changes in representations of men in French society at this
      time.

PMID- 21714202
TI  - Wartime rugby and football: sports elites, French military teams and
      international meets during the First World War.
AB  - The First World War is traditionally considered in history as a temporary halt
      for cultural and sporting activities. If the Olympic Games and the Tour de France
      were actually cancelled, football and rugby were in fact stimulated by the
      circumstances of war. Indeed, the gathering of allied nations behind the Western
      Front emerged as the main factor in the development of these two sports. Reading
      the sporting press and military archives shows that international sporting
      exchanges were stimulated during the Great War. To be specific, France benefited
      from the golden opportunity provided by the presence of the masters of the game
      to strengthen its practices and affirm its status as a sporting nation. Inter
      allied sporting exchanges were primarily characterised by informal encounters
      between military selections. Then, following the recognition of these sports by
      the military authorities, the number of exchanges increased. At the end of 1917,
      the official status acquired by sport within the military forces created the
      conditions for the structuring of the French sporting elite. From that point, we
      can witness the birth of the first French military rugby and football teams, as
      they demonstrate, through their good performances during the demobilisation
      period, the progressive build-up of the international dimension of French sport
      during the war years.

PMID- 21714203
TI  - Boccioni's coin.
AB  - The Ardito was a fighter as well as a competitor whose status as a 'warrior' was
      based on courage and superior physical performance: a superior man. In addition,
      his exuberant conduct, both on and off the battlefield, introduced a significant
      new sub-culture into post-war Italian society, contributing to the attachment of
      notable value to virility and Mussolini's cult of the 'strong man'. The purpose
      of this research is to analyse the impact of this 'arditismo' (spirit of daring)
      on the early post-war period in particular, including the different 'male image'
      of the Italian citizen, and to study the sense of virility in the transition from
      the liberal, easy-going 'Little Italy' of Giovanni Giolitti (1842-1928) to a
      manly, combative, and ambitious nation. Together with some of the vitalistic
      tendencies in the Futurist movement, the main characteristics and mentality of
      the ex-Ardito (former Special Forces) would thus be significantly influential in
      the ideology of nascent Fascism. Indeed, the 'arditismo' influence, together with
      the article and social movement known as Futurism would constitute the two most
      highly structured foundations of early Fascist culture, bringing a political and
      social revolution necessary to create a 'new man'. It was as if the Arditi and
      the new method of military training had transferred their experience from the
      military into civilian life, contributing to a renewal of the image of the
      Italian male in the collective imagination. Indirectly, the image of women would
      also begin to absorb and adapt to new sports models imported from abroad, which
      would create for the Italian Ardito, a grudgingly tolerated rival. The main
      sources for this paper are the archives of the Historical Office of the Army,
      advertising and manuals from the late nineteenth to the early twentieth century,
      placards and graphic publicity from books and journals or private collections,
      and exhibition catalogues.

PMID- 21714204
TI  - Modern pentathlon and the First World War: when athletes and soldiers met to
      practise martial manliness.
AB  - In the nationalistic atmosphere of the early twentieth century, a nurturing
      medium for sports practising martial manliness abounded throughout Europe. This
      framework supported the invention of a new multi-disciplinary sport, aided by
      Baron Pierre de Coubertin himself: modern pentathlon. Though the idea of a new
      form of pentathlon was already born in 1894, it took 30 years, until Paris 1924,
      to establish modern pentathlon within the Olympic Games. This study is concerned
      with the reasons for that delay. It will be assessed whether the active military
      preparations around the First World War and the contemporary image of masculinity
      had a decisive influence on the early history of modern pentathlon. By including
      historical documents from the IOC archives in Lausanne, Switzerland, the research
      office for military history in Potsdam, Germany, and the LA84 Foundation in Los
      Angeles, USA, as well as literature on gender, military sport and Olympic
      history, this study offers an entirely new view on the early history of a sport
      that was born in an atmosphere of glorifying manliness and apparent militarism.
      The history of modern pentathlon thereby provides a particularly appropriate area
      for the analysis of connections between sport, militarism and masculinity. It was
      not by chance that the implementation of a combined sport, which included besides
      swimming and running the three military disciplines of shooting, fencing and
      horse riding, arose in a pre-war context. Though in 1912 the Great War had not
      yet begun, the awareness of an upcoming battle was rising and led to a higher
      attention to Coubertin's almost forgotten assumption of a new sport. In 1924 the
      advantages were finally admitted on two sides: the army recruited modern
      pentathletes as future military officers; the sports community appointed skilled
      officers as successful competitors. Thus the lobby for an Olympic recognition of
      modern pentathlon was found.

PMID- 21714205
TI  - [Drug development and future scope to BCR-ABL inhibitor for chronic myeloid
      leukemia].

PMID- 21714206
TI  - [The role of allogenic hematopoietic stem cell transplantation for chronic
      myeloid leukemia in imatinib era].

PMID- 21714207
TI  - [Temporal orientation and a course of alcohol addiction therapy].
AB  - AIM: The aim of the study was assess the meaning of preferred temporal
      orientation for results of alcohol dependence therapy. METHODS: One hundred and
      sixteen (116) (95 men and 21 women) alcohol addict patients were evaluated at the
      beginning of the alcohol addiction outpatient therapy. The temporal orientation
      and attitude for time was assessed by using Temporal Orientation Questionnaire
      AION and Carpe Diem, Fatalism and Hedonism Scale by Sobol-Kwapinska. RESULTS: The
      results showed that alcohol addict patients were in the highest degree focused on
      the past and the present in the hedonism and fatalism dimensions, while being
      relatively focused in the lowest degree on the present carpe diem dimension and
      the future at the beginning of the therapy. Men and women at the beginning of the
      therapy varied in some dimensions of temporal orientation. The differences
      occurred also between patients who finished and discontinued alcohol dependence
      therapy. CONCLUSIONS: Patients at the begging of alcohol addiction therapy prefer
      past and present temporal orientation. 1. There are differences between temporal
      orientation preferred by men and women. 2. Future temporal orientation is
      beneficial to finish addiction therapy by addict men. 3. Women who finish therapy
      are focused more on the past and hedonistic present orientation than women who
      discontinued therapy.

PMID- 21714208
TI  - [Prevalence of depressive disorders in patients with end-stage renal failure].
AB  - AIM: The depressive symptoms are common in patients with end-stage kidney disease
      but they are often undiagnosed and can complicate the renal replacement therapy.
      The aim of this study was to identify significant differences in frequency and
      severity of depressive symptoms among patients with end-stage renal disease
      depending on what form of treatment they are undergoing--hemodialysis, peritoneal
      dialysis and patients after kidney transplantation. METHODS: 323 patients with
      end-stage renal failure were examined. Among them 206 patients were hemodialysed,
      64--undergoing the peritoneal dialysis and 53 patients were the recipients of
      kidney transplants. We used a self-constructed questionnaire and Beck Depression
      Inventory (BDI). RESULTS: Beck Depression Inventory reflects mild and moderate
      intensification of symptoms. The results obtained by the use of BDI show the mild
      and moderate intensification of the depressive symptoms in the study group. The
      majority of patients suffering from depression were found in the group of
      patients undergoing peritoneal dialysis, to a lesser degree in the hemodialysis
      subgroup and among these, depression had moderate intensity. Patients after
      kidney transplantation were found to be at a smaller risk of depression comparing
      to dialysed patients. CONCLUSIONS: End-stage renal disease may affect the
      occurrence of depressive symptoms, the treatment may also play a role in the
      formation and intensity. We formulated the conclusions of our study carefully,
      taking into account a multitude of other existing causal factors.

PMID- 21714209
TI  - [Differences in sense of coherence in difficult and aspirin-induced asthma and
      it's links with severity of panic and depressive symptoms in subgroups of women
      and men].
AB  - AIM: The author examined psychiatrically a group of 106 patients with difficult
      asthma and 100 patients with aspirin-induced asthma. The special interest of the
      study were differences in sense of coherence in both groups and it's links with
      severity of panic and depressive symptoms in subgroups of asthmatic women and
      men. METHODS: 106 consecutive adults with confirmed, physician-diagnosed
      difficult asthma and 100 patients with aspirin-induced asthma underwent
      psychiatric interview and assessment using M.I.N.I 5.0, Beck Depression Inventory
      (BDI), Panic And Agoraphobia Scale (PAS) and Sense of Coherence Scale (SOC-29).
      Psychiatric assessment was performed by an experienced liaison psychiatrist
      according to ICD-10 and DSM-IV diagnosis. In the difficult asthma group, there
      were 78 women (74%) and 28 men (26%). The average age was 51.3 (SD = 14.5) for
      women and 47.5 (SD = 12.7) for men. In aspirin induced asthma group there were 66
      women (66%) and 34 men (34%). The average age was 52.7 (SD = 12.3) for women and
      48.8 (SD = 13.0) for men. RESULTS: In both groups of asthmatic patients women
      were the majority (74% with difficult asthma and 66% with aspirin-induced asthma)
      with a much higher level of anxiety and depressive symptoms than men. General
      coherence and coherence measured in all three sub-scales were lower in the
      difficult asthma group, especially in women with severe panic and depressive
      symptoms. CONCLUSIONS: It is possible that differences of coherence affect the
      development, course and severity of anxiety and depressive symptoms in asthmatic
      women and men. It may play a special role in development of difficult asthma
      especially among women.

PMID- 21714210
TI  - [Validation of the Polish version of the Athens Insomnia Scale].
AB  - AIMS: To validate the Polish version of the Athens Insomnia Scale (AIS), the
      instrument designed for quantitative measurement of the severity of insomnia
      based on the ICD-10 criteria. METHOD: The AIS was administered to 356 subjects:
      160 patients from the sleep clinic presenting with ICD-10 non-organic insomnia
      (90f; mean age: 44.9 +/- 15.7y) and 196 self-defined good sleepers (106f; mean
      age: 43.9 +/- 13.4y). To assess psychometric properties of the scale, principal
      component analysis, Cronbach's alpha, Pearson's correlation (test-retest
      reliability: two weeks interval; n = 48) and sensitivity-specificity analysis
      were computed. RESULTS: Using the factor analysis only one factor was extracted,
      which accounted for 60.2% of the variance. The internal consistency (Cronbach's
      alpha = 0.90) and the test-retest reliability (r2 = 0.92) of the AIS were found
      to be very satisfactory. These values remain practically unchanged when any of
      the items was removed from the analysis. As expected, subjects with insomnia
      scored significantly higher on the AIS than good sleepers (14.2 +/- 3.9 pts vs.
      4.8 +/- 3 pts; t = 24.9; p < 0.001). Considering the balance between sensitivity
      and specificity, a score of 8 was indicated as the optimum cut-off, with 89%
      overall correct case identification--94% patients with insomnia and 84% healthy
      controls. CONCLUSIONS: Standardisation of the diagnostic process of insomnia is a
      highly important task in clinical practice, epidemiological considerations and
      treatment outcomes assessment. The AIS is a brief, self-reported measure of
      insomnia that may improve these assessments. The good psychometric properties of
      the Polish version of the AIS were confirmed in the present study.

PMID- 21714211
TI  - [Validation of the Patient Health Questionnaire-9 Polish version in the
      hospitalised elderly population].
AB  - AIM: The first aim of this study was to evaluate the diagnostic validity of the
      Polish version of the PHQ-9 in hospitalised elderly Polish patients. The second
      aim was to find an optimal cutoff score for PHQ-9 to screen for a major
      depressive episode (MDE) (according to the Short Geriatric Depression Scale -
      SGDS). METHOD: The PHQ-9, SGDS and a personal questionnaire were all administered
      to patients age 60 and above, who were hospitalised in our clinic. RESULTS; One
      hundred five people were examined (51.4% women) (mean age +/- SD 73.4 +/- 7.9
      years). According to the PHQ-9 36(34.3%) people had MDE. The PHQ-9 showed
      significant positive internal consistency (Cronbach's alpha = 0.7) and the scores
      of each of its nine items positively correlated (0.31-0.68; p < 0.05) with the
      total score. The convergent validity with the SGDS was significantly positive (r
      = 0.58; p < 0.05). Using > 6 pts as the cutoff point, the sensitivity and
      specificity of the PHQ-9 for recognising MDE (according to SGDS) were found to be
      70.4% and 78.2% respectively. CONCLUSIONS: The Polish version of the PHQ-9 is a
      valid and useful tool for depression screening and a score of > 6 is the optimal
      cutoff point for the hospitalised elderly

PMID- 21714212
TI  - [Sexological questionnaire for screening research. Theory and validity].
AB  - AIM: The aim of the research was to construct a questionnaire basing on the
      presently standing criteria of sexual dysfunctions and sexual disorders
      (according to ICD-10), that would enable the diagnosis of symptoms, as well as to
      verify its validity. METHOD: 102 patients (46 women and 56 men, mean age of
      32.09, SD = 10.29) of sexological clinics who declared they had symptoms of
      sexual dysfunctions or disorders were asked to participate and fill in the
      questionnaire which was later evaluated in a clinical study on the basis of ICD
      10 research criteria. RESULTS: Results show that using the questionnaire enables
      the diagnosis of 100% of gender identity disorders, almost all sexual
      dysfunctions and disorders connected to sexual orientation. The sensibility and
      specificity of the questionnaire were also examined and proved very high.
      CONCLUSIONS: The Sexological questionnaire for screening research presents with
      good validity, sensibility and specificity.

PMID- 21714213
TI  - [Factor structure of symptoms in the Krakow Depression Inventory KID IO "B1"
      among 15-year-olds].
AB  - AIM: The aim of the article is to partially verify the theoretical concept of
      depressive symptoms in adolescents, based on KID IO "B1", as well as to check the
      accuracy of the questionnaire. METHOD: The KID results from an untreated sample
      population of 15-year-olds were statistically analysed. Of the 1118 KID IO "B1"
      questionnaires submitted, 594 (246 boys and 348 girls) underwent factor analysis,
      of which 297, i.e. half, gained a result higher than the diagnostic threshold for
      depression. In search of the presence of general factors, as well as to verify
      the principles used to categorise depressive symptoms according to clinical
      criteria, analysis of the factors using methods consisting of oblimin, quatrimax
      and varimax rotations was carried out separately and combined for both genders.
      RESULTS: The following new factors were distinguished for boys: I--lowered mood,
      and anxiety, II--self-destruction, III--apathy, cognitive disturbances, IV-
      somatic symptoms, V--somatisation, apathy, self-destruction, VI--boredom and
      avoidance of social contact, and for girls: I--lowered mood, lack of
      consideration for future repercussions, II--lowered drive, learning difficulties,
      cognitive and motivational disturbances, III--anxiety, IV--dysphoria with self
      destruction, V--self-destruction, VI--eating pattern disturbances. CONCLUSIONS:
      Depression, as derived from factor analysis of the KID IO "B1" questionnaire
      positions, is heterogeneous. Theoretical division of symptom groups, relating to
      the specific scale in the questionnaire, was confirmed to a very small degree
      through the analysis of the factors. The list of factors in genders differs. The
      groups of symptoms appearing in both genders gained from analysis are different
      in boys and girls with one exception, which may partially result from the
      different factor overviews of depressive symptoms in both genders.

PMID- 21714214
TI  - [Adaptation of psychodrama in psychotherapy of patients with anorexia nervosa and
      bulimia nervosa].
AB  - The aim of the article was an attempt to present selected theoretical motifs and
      moreover self experience in the adaptation of elements of psychodrama by Moreno
      in psychodynamic psychotherapy (individual and group psychotherapy) in a group of
      people with anorexia and bulimia nervosa. Psychodrama through own creativity,
      spontaneity and taking action on the "here and now" stage helps to attain and
      intensify therapeutic aims which concern the consciousness of inner conflict of
      persons with anorexia and bulimia nervosa, which is translocated on their body.

PMID- 21714215
TI  - [Dancing manias. Between culture and medicine].
AB  - Dancing mania is a clinical and cultural phenomenon which occurred in Western
      Europe between 13th and 18th centuries. The term dancing mania is derived from
      the Greek words choros, a dance, and mania, a madness. An Italian variant was
      known as tarantism as victims were believed to have been bitten by tarantula
      spider. Although symptoms of dancing manias were well documented in contemporary
      writings the exact aetiology of dancing plaques is still unclear. Several causes
      for dancing mania have been postulated: demonic possession, the bite of
      tarantula, ergot poisoning, epilepsy, mass hysterias, exotics religious cults.
      The article contains a review of hypothesis of epidemic dances included both
      medical and psychological factors.

PMID- 21714216
TI  - [Jerusalem syndrome. Symptoms, course and cultural context].
AB  - The Jerusalem syndrome is an acute psychotic state observed in tourists and
      pilgrims who visit Jerusalem. The main symptom of this disorder is identification
      with a character from the Bible and exhibiting behaviours which seems to be
      typical for this character. The article presents an overview of cultural and
      demographic factors associated with the appearance of the Jerusalem syndrome.
      Three main categories of the syndrome were identified with special focus on the
      category unconjoined to previous psychopathology which can be described as the
      'pure' form of the Jerusalem syndrome. The main diagnostic criteria for the
      'pure' type and the sequence of seven clinical stages of the Jerusalem syndrome
      were described. The article contains a review of the hypothesis about the causes
      of Jerusalem syndrome with special attention given to the role of places of
      particular meaning for religious tradition.

PMID- 21714217
TI  - [Advance in interferogram data processing technique].
AB  - Fourier transform spectrometry is a type of novel information obtaining
      technology, which integrated the functions of imaging and spectra, but the data
      that the instrument acquired is the interference data of the target, which is an
      intermediate data and couldn't be used directly, so data processing must be
      adopted for the successful application of the interferometric data In the present
      paper, data processing techniques are divided into two classes: general-purpose
      and special-type. First, the advance in universal interferometric data processing
      technique is introduced, then the special-type interferometric data extracting
      method and data processing technique is illustrated according to the
      classification of Fourier transform spectroscopy. Finally, the trends of
      interferogram data processing technique are discussed.

PMID- 21714218
TI  - [Progress of light extraction enhancement in organic light-emitting devices].
AB  - Organic light emitting devices (OLEDs) have been used in flat-panel displays and
      lighting with a near-30-year development. OLEDs possess many advantages, such as
      full solid device, fast response, flexible display, and so on. As the application
      of phosphorescence material, the internal quantum efficiency of OLED has almost
      reached 100%, but its external quantum efficiency is still not very high due to
      the low light extraction efficiency. In this review the authors summarizes recent
      advances in light extraction techniques that have been developed to enhance the
      light extraction efficiency of OLEDs.

PMID- 21714219
TI  - [Current progress in food geographical origin traceability by near infrared
      spectroscopy technology].
AB  - The geographical origin traceability of food, an important part of traceability
      system, is effective in protecting the quality and safety of foodstuffs. Near
      infrared spectroscopy (NIR), which is a powerful technique for geographical
      origin traceability, has attracted extensive attention by scientists due to its
      speediness, non-pollution and simple operation. This paper presents the
      advantages and disadvantages of techniques that have been used for food
      geographical origin traceability. The basic principles of NIR and its
      applications in different food geographical origin traceability are presented
      too. Furthermore, problems in applications are analyzed and the future
      development trends are discussed.

PMID- 21714220
TI  - [Low driving voltage in organic light-emitting diodes with NPB/MoO3/NPB as a hole
      transport layer].
AB  - Driving voltage of organic light-emitting diodes (OLEDs) was lowered by applying
      (NPB/MoO3)(x)/NPB as a hole transport layer (HTL). (NPB/MoO3)(x) was multi-layer
      periodic (MLP) structure with x changed from 0 to 3. Compared with the
      conventional device with 0-periodic structure, the driving voltage of the device
      with 1-periodic structure was the lowest. This was due to charge transfer (CT)
      complex formation between NPB and MoO3. The driving voltage of tris (8
      hydroxyquinoline) aluminum (Alq3)-based organic light-emitting devices (OLEDs)
      could be lowered by 0. 8 V at 1 000 cd x m(-2) by using multiple structure of
      NPB/MoO3/NPB.

PMID- 21714221
TI  - [Effects of hole-injection layers on the performance of blue organic light
      emitting diodes].
AB  - The present work investigates the effects of different buffer layers on the
      performance of blue organic light-emitting diodes (OLEDs), and compares them with
      the device with no buffer layer. Two kinds of blue OLEDs with 4,4'-bis(2,2'
      diphenyl vinyl)-1,1'-biphenyl (DPVBi) as the emitting layer, N, N'-bis-(1
      naphthyl)-N, N'-1-diphenyl-1,1 '-biphenyl-4, 4'-diamine (NPB) as the hole
      transporting layer, and copper phthalocyanine (CuPc) and poly(3,4
      ethylenedioxythiophene) : poly (styrenesulphonate) PEDOT : PSS as the hole
      injection layer respectively were fabricated with the structures of
      ITO/CuPc/NPB/DPVBi/BCP/Alq3 /Al and ITO/PEDOT : PSS/NPB/DPVBi/BCP/Alq3/Al.
      Moreover, the effects of different preparation technology of CuPc on the
      performance of OLEDs were also investigated. It was found that the performance of
      the devices with a hole injection layer is better than that of the device without
      any hole-injection layer. Although the luminance and efficiency of the water
      soluble CuPc based device are worse than that of the device with thermally
      evaporated CuPc, but better than that of the device with water-soluble PEDOT :
      PSS. So the water-soluble CuPc is a good hole injection material because it is
      easier to fabricate the film than traditional CuPc.

PMID- 21714222
TI  - [Synthesis of the Zn2SiO4 : Eu3+ red phosphor by sol-gel method].
AB  - Spherical Zn2 SiO4 : Eu3+ phosphors were prepared by a Pechini sol-gel process.
      The microstructure and luminescent properties of the obtained Zn2 SiO4 : Eu3+
      particles were well characterized by X-ray diffraction (XRD), Fourier transform
      infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy
      dispersive X-ray spectroscopy (EDS) and photoluminescence (PL) spectra. The
      results of SEM demonstrated that the Zn2 SiO4 : Eu3+ particles with a diameter
      about 1 -3microm, which have spherical morphology, emitted an intensive red light
      emission at 613 nm under excitation at 395 nm. Besides, the effects of the Eu3+
      concentration, annealing temperature and charge compensators of Li+ ions on the
      PL emission intensities were investigated in detail. The investigation showed
      that the PL intensity increased with the annealing temperature increasing. At the
      same time, the PL intensity firstly increased and then decreased with the Eu3+
      and Li+ concentration increasing.

PMID- 21714223
TI  - [Mid-infrared emission properties of Ho3+/Tm(3+)-codoped Ge-Ga-S-CsI glasses].
AB  - A serial of chalcogenide glasses based on 78GeS2-12Ga2S3-10CsI (in molar%) system
      doped with the different radios of Ho3+/Tm3+ ions were synthesized by melt
      quenching method. Their absorption spectra and mid-infrared fluorescence under
      808 nm laser excitation were measured. According to Judd-Ofelt theory, the
      intensity parameters omega(i) (i = 2, 4, 6), spontaneous transition probabilities
      A(rad) and radiative lifetomes tau(r) for Ho3+ ion were calculated. Absorption
      cross-sections sigma(a), emission cross-sections sigma(e) and gain coefficient
      G(lambda) corresponding to the emission of Ho3+ ions at 2.0 microm were obtained.
      By changing the Tm3+ concentration, the energy transfer regime of Tm3+ and Ho3+
      ions under 808 nm excitation was investigated. The results show that Ho3+/Tm(3+)
      codoped Ge-Ga-S-CsI glasses would be a potential material for 2.0 microm
      emission.

PMID- 21714224
TI  - [The influence of argon fraction on the emission spectroscopy of air dielectric
      barrier discharge].
AB  - The emission spectra of air dielectric barrier discharge were measured through
      dielectric barrier discharge experiment system, and the influence of argon
      fraction on the emission spectra of air dielectric barrier discharge was studied
      in the present paper. In the wavelength range of 280-500 nm, the second positive
      band system of nitrogen N2 (C3 pi(u)-B 3 pi(g)) and the first negative band
      system of nitrogen ion N2+ (B 3sigma(u)(+) -X 2 sigma(g)+) were found. Adding 10%
      argon under the same conditions, initial discharge voltage reduced from 26 to 23
      kV, both dielectric barrier discharge and its emission spectra intensity were
      enhanced, and the full width at half maximum increased. With increasing argon
      fraction, the trends of each nitrogen second positive band system line were
      different and two nitrogen ion first negative band system lines (391.44 and
      427.81 nm) were reduced.

PMID- 21714225
TI  - [Measurement of refractive index with a PM-LPG based Sagnac loop sensor].
AB  - By inscribing a long-period fiber grating (LPG) on a polarization-maintaining
      fiber (PMF), a fiber Sagnac loop sensor for simultaneous measurement of
      refractive index and temperature has been proposed and demonstrated. The LPG was
      fabricated on the PMF by using a CO2 laser, and then inserted into a fiber loop
      formed by using a normal single-mode fiber coupler. One of the transmission
      minimum of the Sagnac loop sensor was measured, whose wavelength varied with
      temperature and the intensity changed with refractive index. Temperature
      sensitivity of -0.654 nm x degrees C(-1) and refractive sensitivity of 49.9 dB x
      RIU(-1) have been achieved. The sensor system shows advantages of small size and
      low cost, and owns a good application prospect.

PMID- 21714226
TI  - [THz time-domain spectroscopic study of composites filled with different carbon
      black].
AB  - Composites were prepared by filling high density polyethylene (HDPE) with
      acetylene black (AC-CB) and high-structure CB (HG-CB), respectively. Optical
      properties of the composites were characterized with terahertz time-domain
      spectroscopy (THz-TDS). It was found that as frequency increases the absorption
      coefficients of the composites increase whereas the refractive indexes decrease.
      Both the absorption coefficient and refractive index increase with increasing the
      particle concentration. The HG-CB filled composites have larger absorption
      coefficient but smaller refractive index compared with that of the AC-CB
      composites at the same particle concentration. These phenomena are related to the
      different particulate structures and aggregate structures of the CB particles.
      Assuming that the dielectric loss in THz frequency range is mainly attributed to
      the electron transport within the conductive clusters and the interfacial
      polarization of HDPE, the information of relaxation time and relaxation strength
      was obtained through fitting the experimental results to two-Debye theory of
      dipole relaxation.

PMID- 21714227
TI  - [Analysis of urban thermal environment change characteristics during the total
      solar eclipse].
AB  - There was a very good observation area in Chongqing for the total solar eclipse
      along the Changjiang river on 22 July, 2009. Through the experiments, the outdoor
      meteorological data (solar radiation, air temperature and relative humidity) were
      observed and recorded on 21 July and 22 July. Based on the experimental
      observation data, the effect of thermal environment in Chongqing area was to
      analyzed and discussed. Experiment indicates that the reduction of air
      temperature and surface temperature resulted in the decrease in the solar
      radiation intensity, and the amplitude of the air temperature change is 2.4
      degrees C during the total solar eclipse. Compared with the two days' air
      temperature, the amplitude of the air temperature change reached 4.6 degrees C on
      account of the total solar eclipse.

PMID- 21714228
TI  - [The highest proportion of tobacco materials in the blend analysis using PPF
      projection method for the near-infrared spectrum and Monte Carlo method].
AB  - The present paper builds a model based on Monte Carlo method in the projection of
      the blending tobacco. This model is made up of two parts: the projecting points
      of tobacco materials, whose coordinates are calculated by means of the PPF
      (projection based on principal component and Fisher criterion) projection method
      for the tobacco near-infrared spectrum; and the point of tobacco blend, which is
      produced by linear additive to the projecting point coordinates of tobacco
      materials. In order to analyze the projection points deviation from initial state
      levels, Monte Carlo method is introduced to simulate the differences and changes
      of raw material projection. The results indicate that there are two major factors
      affecting the relative deviation: the highest proportion of tobacco materials in
      the blend, which is too high to make the deviation under control; and the
      quantity of materials, which is so small to control the deviation. The conclusion
      is close to the principle of actual formulating designing, particularly, the more
      in the quantity while the lower in proportion of each. Finally the paper figures
      out the upper limit of the proportions in the different quantity of materials by
      theory. It also has important reference value for other agricultural products
      blend.

PMID- 21714229
TI  - [Detection of pear injury based on visible-near infrared spectroscopy and
      multispectral image].
AB  - A new approach to detect the injury degree and time of pear based on visible-near
      infrared spectroscopy and multispectral image has been proposed. Firstly, visible
      near infrared spectroscopy combined with partial least squares (PLS) and least
      squares-support vector machine (LS-SVM) was used for pear injury degree and time
      prediction. The result indicated that these two methods both have good
      performances in predicting pear injury degree in the late period. The LS-SVM
      method is more accurate in predicting the injury time of light pear injury, but
      its overall result of injury time prediction is not as good as that for the PLS
      method. Then, the multispectral image was used to predict the time of pear
      injury. The result shows that for different degrees of pear injury, the
      prediction models based on LS-SVM have a better performance with correlation
      coefficients around 5.85. The result of this study can be used to detect the
      injury degree and time of pear rapidly and non-destructively, and provide a new
      approach to pear classification.

PMID- 21714230
TI  - [Tobacco plant parts similarity analysis based on near-infrared spectroscopy and
      SIMCA algorithm].
AB  - The appearance features of tobacco reflect its inner quality. Many factors, such
      as different plant parts, variety and maturity, provide standard and foundation
      for tobacco production processing. According to the different position of tobacco
      plant parts, tobacco plants leaves can be divided into five parts as tip, upper
      middle, middle, lower-middle and priming leaf respectively. Five hundred tobacco
      leaf samples (100 each for one of five tobacco plant parts) from Yunnan province
      in 2008 were collected using near infrared spectroscopy, which all belong to
      tobacco varieties of K326. The similarity analysis of tobacco plant parts was
      carried out using mathematical model of SIMCA similarity analysis. The conclusion
      showed that the tobacco plant parts similarity results based on near-infrared
      spectroscopy corresponded to the relative tobacco plant parts in Yunnan province.
      The farther two tobacco plant parts were away from each other, the lower the
      similarity of corresponding parts was. And the similarity results of adjacent
      tobacco plant parts were different. The study discussed a method of confirming PC
      numbers and realized the quantitative similarity analysis between classes. It is
      instructive in replacement or adjustment of tobacco leaf blending and evaluation
      of tobacco industrial grading.

PMID- 21714231
TI  - [Exploration of the broken parts of a brake hose by ATR-FTIR and SEM].
AB  - ATR-FTIR and SEM were respectively utilized to analyze the chemical components
      and to observe the micromorphology of a broken brake hose from a traffic case,
      which could be a supplementary for the traditional microscopic examination. The
      instrumental analysis results indicated that the rubber from the brake hose had
      already aged; the rubber from external side had experienced brittle fracture and
      there were original hollows in the rubber from internal side. The breaking of the
      brake hose resulted from all these reasons. The experimental results also
      demonstrated that the fact could be reflected efficiently, accurately and
      objectively by the application of ATR-FTIR and SEM to the physical evidence from
      a case. Therefore, it could be an effective complement for traditional traffic
      trace examination.

PMID- 21714232
TI  - [Early stage diagnosis of endometrial cancer based on near infrared spectroscopy
      and support vector machine].
AB  - Near-infrared spectroscopy combined with chemometrics methods for diagnosis of
      cancer has been reported in literatures. In our study, the NIR spectra of 77
      specimens of different physiological stages of endometrium were collected.
      Spectral data were pretreated firstly by multiplicative scatter correction (MSC),
      orthogonal signal correction (OSC), and both of them, respectively, and then by
      SG smoothing. Latin partition method was used to select 3/4 samples as a training
      set, and the other 1/4 samples for test set. Support vector machine (SVM) model
      was built for classification, and the classification results was compared with
      that of partial least squares (PLS) model based on the same pretreatment methods.
      Samples of malignant, hyperplasia and normal endometrium were classified better
      by SVM (classification accuracy was 92%) than PLS (classification accuracy was
      90%). The results suggested that classification accuracy was affected by
      pretreatment methods and models. SVM combined with endometrial tissue near
      infrared spectroscopy is expected to develop into a new approach to tumor
      diagnosis.

PMID- 21714233
TI  - [Application of near infrared spectral fingerprint technique in lamb meat origin
      traceability].
AB  - Near infrared spectra of 99 lamb meat samples from three pasturing areas and two
      farming areas of China were scanned and analyzed to seek a cheap, rapid and
      effective method for lamb meat origin traceability. Two chemometric methods
      including linear discriminant analysis based on principal component analysis
      (PCA+LDA) and partial least squares discriminant analysis (PLS-DA) were used to
      develop the discriminate models. It was showed that there were significantly
      differences among the lamb meat samples from five regions based on NIR spectra
      after second derivative (Savitzky-Golay, 9 point) and multiplicative scattering
      correction (MSC) transformation in the whole wavelength. The discrimination of
      two models was best for classification of pasturing area and farming area, with
      both correctly classified by 100%. The correct classification rate of samples
      from five different regions using PCA+LDA model was 91.2%, higher than using PLS
      DA model (76.7%). These results demonstrate that near infrared reflectance
      spectroscopy (NIRS) combined with chemometric analysis can be used as an
      effective method to classify lamb meat according to its geographical origin.

PMID- 21714234
TI  - [TG-FTIR study on pyrolysis of wheat-straw with abundant CaO additives].
AB  - Biomass pyrolysis in presence of abundant CaO additives is a fundamental process
      prior to CaO sorption enhanced gasification in biomass-based zero emission
      system. In the present study, thermogravimetric Fourier transform infrared (TG
      FTIR) analysis was adopted to examine the effects of CaO additives on the mass
      loss process and volatiles evolution of wheat-straw pyrolysis. Observations from
      TG and FTIR analyses simultaneously demonstrated a two-stage process for CaO
      catalyzed wheat-straw pyrolysis, different from the single stage process for pure
      wheat-straw pyrolysis. CaO additives could not only absorb the released CO2 but
      also reduce the yields of tar species such as toluene, phenol, and formic acid in
      the first stage, resulting in decreased mass loss and maximum mass loss rate in
      this stage with an increase in CaO addition. The second stage was attributed to
      the CaCO3 decomposition and the mass loss and maximum mass loss rate increased
      with increasing amount of CaO additives. The results of the present study
      demonstrated the great potential of CaO additives to capture CO2 and reduce tars
      yields in biomass-based zero emission system. The gasification temperature in the
      system should be lowered down to avoid CaCO3 decomposition.

PMID- 21714235
TI  - [Study on the fingerprints of magnetitum by FTIR].
AB  - Thirteen different magnetitum samples were analyzed by FTIR, and the FTIR
      fingerprint was set up with them. Processed samples and the crudes were compared
      with the fingerprint. It was found that all the similarities of the samples are
      more than 0.97. The similarities and the correlation coefficients of the
      processed samples are decreased. The FTIR fingerprint could be used for
      evaluating the quality of magnetitum for commodities.

PMID- 21714236
TI  - [Research on nondestructive measurement of soluble tannin content of astringent
      persimmon using visible and near infrared diffuse reflection spectroscopy].
AB  - The objectives of the present study were to establish the relationships of the
      visible and near infrared diffuse reflection (Vis/NIR) spectroscopy and the
      soluble tannin content of internal quality index of astringent persimmon, and to
      evaluate the value of Vis/NIR spectroscopy in measuring the soluble tannin
      content of internal quality index of astringent persimmon. In the spectral region
      between 570 and 1 848 nm, calibration results for the soluble tannin content of
      astringent persimmon were compared with different regression techniques,
      different derivative treatments and different scatter and standard treatments.
      The results showed that the modified partial least squares(MPLS) model, with
      respect to the first derivative D1 log(1/R) and detrend only, provided better
      prediction performance for the soluble tannin content of astringent persimmon
      fruit, with the correlation coefficient of cross validation of calibration
      (R(cv)) and correlation coefficient of prediction (R(p2)), the root mean square
      error of cross validation of calibration (RMSECV) and the root mean square error
      of prediction (RMSEP) of 0.722 7, 0.678 5, 0.148, and 0.176 3 respectively. The
      preliminary research on the built models indicated that nondestructive
      measurement of the soluble tannin content of astringent persimmon using Vis/NIR
      spectroscopy technique was feasible, but the precision of the models could be
      improved further.

PMID- 21714237
TI  - [The evaluation of hydrocarbon potential generation for source rocks by near
      infrared diffuse reflection spectra].
AB  - Near-infrared (NIR) and mid-infrared (MIR) diffuse reflection spectra were
      compared and evaluated for hydrocarbon potential generation of source rocks. Near
      infrared diffuse reflectance often exhibits significant differences in the
      spectra due to the non-homogeneous distribution of the particles, so the signal
      to-noise ratio of NIR is much lower than MIR It is too difficult to get accurate
      results by NIR without using a strong spectral preprocessing method to remove
      systematic noise such as base-line variation and multiplicative scatter effects.
      In the present paper, orthogonal signal correction (OSC) and an improved
      algorithm of it, i.e. direct orthogonal signal correction (DOSC), are used as
      different methods to preprocess both the NIR and MIR spectra of the hydrocarbon
      source rocks. Another algorithm, wavelet multi-scale direct orthogonal signal
      correction (WMDOSC), which is a combination of discrete wavelet transform (DWT)
      and DOSC, is also used as a preprocessing method. Then, the calibration model of
      hydrocarbon source rocks before and after pretreatment was established by
      interval partial least square (iPLS). The experimental results show that WMDOSC
      is more successfully applied to preprocess the NIR spectra data of the
      hydrocarbon source rocks than other two algorithms, and NIR performed as good as
      MIR in the analysis of hydrocarbon potential generation of source rocks with
      WMDOSC-iPLS pretreatment calibration model.

PMID- 21714238
TI  - [Mice scald model investigated by OCT combined with reflection spectrum].
AB  - OCT combined with reflective spectrum was employed to precisely evaluate the mice
      scald model. Under the conditions that the temperature increased by 5 degrees C
      from 60 to 95 degrees C with 20 s thermal effect, the cutis depth linearly
      increased. The fitting absorption parameters and the gradients showed the V
      trends. Wave peaks of first order differential were legible from 65 to 85 degrees
      C, then wave peaks became worse over 85 degrees C. At color coordinates, red
      value decreased severely from 65 to 85 degrees C and from 90 to 95 degrees C,
      green value continuously decreased, but blue value increased. Under the
      conditions that thermal effect time increased from 10 to 40 s at 90 degrees C,
      the main changes of above factors happened at about 20 s, and after 20 s effect
      time the change of these factors was weak. These factors could reflect the form
      and progresses of zones of coagulation, injury of cutis and hypodermis. So OCT
      combined with reflection spectrum could provide a novel method that can be
      applied for the real-time, low-cost, in vivo and noninvasive optical biopsy on
      scald.

PMID- 21714239
TI  - [Prediction of the lengths of fibers and vessels of rattans using near infrared
      spectroscopy].
AB  - The morphological characteristics of fibers and vessels of six rattan species in
      Southern China were investigated to study the feasibility of predicting the
      lengths of fibers and vessels of rattan species with application of analytical
      technologies of near infrared spectroscopy (NIR). The results showed that the
      average lengths of fibers and vessels of six rattan species were from 1 229 to 1
      917 mm and from 1 035 to 2 129 mm, respectively. The models of length of fiber
      and vessel were constructed by combining partial least square (PLS) and full
      cross-validation, and a good correlation between the length of fibers and the
      spectrum transformed by the first derivative was found within the spectral range
      of 350 - 2 454 nm, and the correlation coefficient (r(c) and r(p)) and standard
      error (SEC and SEP ) of calibration model and prediction model are 0.98, 0.85 and
      70, 178 respectively, while a good correlation between the length of vessels and
      the spectrum transformed by the first derivative was found within the spectral
      range of 350-2 500 nm, the correlation coefficient (r(c) and r(p)) and standard
      error (SEC and SEP) of calibration and prediction model is 0.97, 0.80 and 101,
      261 respectively. Their model parameters showed that NIR spectroscopic technique
      can rapidly and accurately predict the lengths of fibers and vessels of the six
      rattan species.

PMID- 21714240
TI  - [Specific interaction study in collagen/hyaluronic acid blends by two-dimensional
      infrared correlation spectroscopy].
AB  - Conformational changes and specific interactions in the collagen/hyaluronic acid
      blends were studied by two-dimensional infrared correlation spectroscopy with the
      interruption of the component of hyaluronic acid in collagen/ hyaluronic acid
      blends. It was found that the synchronous cross-peaks, derived from stretching
      vibrations of C=O at 1 694 cm(-1), wagging of N-H at 1 524 cm(-1) and in-plane
      deformation of N-H at 1 241 cm(-1) of collagen, were indicative of local
      conformational changes of collagen. The synchronous negative cross-peak between
      stretching vibrations of C-OH of hyaluronic acid at 1 045 cm(-1) and streching
      vibrations of C=O of collagen at 1 694 cm(-1) suggested that the interaction of
      hydrogen bonding existing between O-H of HA and C=O of collagen with the content
      of HA varied from 0% to 50%. With the content of HA more than 50%, the cross-peak
      at 1 045 cm(-1) disappeared in synchronous correlation spectra while the
      intensity of cross-peak at (1 694, 1 524), (1 694, 1 241), (1 524, 1 241)
      increased, which indicated that no interaction was found between O-H of HA and
      collagen, however, the interactions of hydrogen bonding existed between C=O of HA
      and N-H of collagen, resulting in the conformational changes of collagen.

PMID- 21714241
TI  - [Study on the wood grading by near infrared spectroscopy].
AB  - The present paper discussed wood grading according to modulus of rupture (MOR) by
      near infrared (NIR) spectroscopy. The calibration model was built between MOR of
      wood and NIR data in the range of 1 000-1 400 nm with partial least square
      regression (PLS). The correlation coefficient (r) was 0.89 and the standard error
      of calibration (SEC) was 6.30 MPa. The MOR of 35 unknown samples was predicted
      using the model. Wood samples were graded according to their predicted values and
      true values. The rate of right prediction for A, B and C was 75.0%, 91.3% and
      80.0% respectively, and the whole rate of right prediction was 88.6%. The result
      has proved that near infrared spectroscopy is a fast method for the determination
      of wood grade in the small clear samples.

PMID- 21714242
TI  - [Study on the processing of leech by FTIR and 2D-IR correlation spectroscopy].
AB  - The chemical differences of traditional Chinese medicine leech before and after
      processing were analyzed by FTIR and two-dimensional correlation infrared (2D-IR)
      spectroscopy. The result showed that the leech was high in protein, with
      characteristic peaks of amide I, II bands. Comparing the IR spectra of samples,
      the primary difference was that the characteristic peak of fresh leech was at 1
      543 cm(-1), while that of crude and processed leech was at 1 535 cm(-1). A 2D-IR
      spectrum with heating perturbation was used to track the processing dynamics of
      leech In the 2D-IR correlation spectra, fresh leech exhibited stronger automatic
      peaks of the amide I and II bands than that of processed leech, which indicates
      that the protein components of the fresh leech were more sensitive to heat
      perturbation than the processed one. Moreover, the result of FTIR and 2D-IR
      correlation spectra validated that the 3-dimensional structure of protein was
      damaged and hydrogen bonds were broken after processing, which resulted in the
      inactivation of protein. The fatty acids and cholesterol components of leech were
      also oxidized in this process.

PMID- 21714243
TI  - [Study on effect of hyperbranched polyester on the mechanical properties and
      morphology of PEG polyurethane elastomer by ATR-FTIR].
AB  - In order to enhance the mechanical properties of polyethylene glycol (PEG)
      polyurethane elastomer, the modified hyperbranched polyester (HBP) was
      introduced. The chemical structures of HBP/PEG polyurethane films were analyzed
      by attenuated total reflection-Fourier transfoum infrared spectrum (ATR-FTIR).
      The results indicate that with the modified hyperbranched polyester added, the
      tensile strength and elongation at break of PEG polyurethane elastomer are
      improved obviously. When the content of hyperbranched polyester of the third
      generation is 0.4%, the resultant elastomer has the best tensile strength, which
      increases 2.53 times. When the content of hyperbranched polyester of the first
      generation rises up to 1.6%, the resultant elastomer has the best elongation at
      break, which increases 1.43 times. The degree of the total hydrogen bonding and
      the degree of microphase separation are increased, which enhance the mechanical
      properties of PEG polyurethane elastomer.

PMID- 21714244
TI  - [Fast determination of malondialdehyde in oilseed rape leaves using near infrared
      spectroscopy].
AB  - Near infrared (NIR) spectroscopy was applied for the fast and nondestructive
      determination of malondialdehyde (MDA) content in oilseed rape leaves. A total of
      90 leaf samples were collected, the calibration set was composed of 60 samples,
      and the prediction set was composed of 30 samples. Different preprocessing
      methods were used before the calibration stage, including smoothing, standard
      normal variate, first and second derivative, and detrending. Then partial least
      squares (PLS) models were developed for the prediction of MDA content in oilseed
      rape leaves. The latent variables selected by PLS and effective wavelengths
      selected by successive projections algorithm (SPA) were used as the inputs of
      least square-support vector machine (LS-SVM) to develop LV-LS-SVM and SPA-LS-SVM
      models. The correlation coefficients (r) and root mean square error of prediction
      (RMSEP) were used as the model evaluation indices. Excellent results were
      achieved by LV-LS-SVM model, and the prediction results by LS-SVM model using
      detrending spectra were r = 0.999 9 and RMSEP = 0.530 2, and those by LS-SVM
      model using 2-Der spectra were r = 0.999 9 and RMSEP = 0.395 7. The results
      showed that NIR spectroscopy could be used for determination of MDA content in
      oilseed rape leaves, and an excellent prediction precision was achieved. This
      study supplied a new approach to the dynamic and continuous field monitoring of
      growing status of oilseed rape.

PMID- 21714245
TI  - [Renewable resource-based composites of thermoplastic acorn starch and
      polycaprolactone: preparation and FTIR spectrum analysis].
AB  - Acorn starch was used as the main material. Thermoplastic acorn starch (TPAS) and
      binary composites of thermoplastic acorn starch(TPAS)/Polycaprolactone (PCL) were
      prepared by hot-melt extrusion method. The effects of different plasticizers such
      as ethylene glycol, glycerol, monoethanolamine, iminobisetnanol and
      triethanolamine on molecular structure of samples were studied by FTIR and XRD
      analysis. In addition, the effects of different plasticizing system on molecular
      structure and mechanical properties of composites were also studied. The results
      showed that the addition of plasticizers changed the inter-molecular structure,
      and glycerol-based TPAS/PCL composites showed favorable mechanical properties.

PMID- 21714246
TI  - [The method of principal component interactive validation in multi-region and its
      application in gas spectrum identification].
AB  - A method of principal component interactive validation in multi-region is
      presented. Based on the characteristic peaks of target gas the full spectral
      region is divided into multiple characteristic regions. In succession the
      principal component analysis around the pure components spectral matrix in
      divided characteristic regions is applied. Thus the potential components included
      in target gas are identified according to the main components number according to
      99% larger cumulated contribution and the descending sorting of maximum value of
      pure component spectrums. After that, the characteristic regions of potential
      components are compared with the ones of target gas one by one. In this way the
      real components of target gas are confirmed. Because the principal component
      analysis was applied in multiple characteristic regions, this method can avoid
      omitted identification. Owning to the matching validation between the
      characteristic absorption regions of target gas and the ones of pure component
      gas this method can avoid additional identification. The simulated and the
      measured spectra both validate the qualitative ability of this method.

PMID- 21714247
TI  - [Raman tweezers-based analysis of carotenoid synthesis in Rhodotorula glutinis].
AB  - Carotenoid synthesis in Rhodotorula glutinis was investigated with Raman tweezers
      in order to find the effect of nitrogen and carbon resource on carotenoid yield.
      The cells in fermentation terminus were harvested, and then divided into two
      parts, one for UV analysis, the other for Raman tweezers detection. Original
      spectra were preprocessed by carrying out background elimination and baseline
      correction, and the averaged spectra of cells cultivated in different
      fermentation medium were analyzed qualitatively. The results showed that the
      Raman intensity of carotenoid were obviously different. There was a high
      correlation between UV results and Raman peak height data, the correlation
      coefficients of fitted parameters were 0.907 8 and 0.912 1, respectively.
      Quantitative analysis of 1 508 cm(-1) peak height indicated that the appropriate
      nitrogen and carbon resources for the growth of Rhodotorula glutinis cells and
      synthesis of carotenoid were yeast extract + tryptone, and glucose, respectively.
      The above results suggest that Raman tweezers can provide information about
      carotenoids in Rhodotorula glutinis cells and serve as an effective tool for real
      time measurement of carotenoid synthesis and optimization of fermentation medium.

PMID- 21714248
TI  - [DFT and surface-enhanced Raman scattering studies of BPA].
AB  - On the base of the vibration theory, the spectrum of bisphenol A(BPA) molecule
      was calculated by the density functional theory(DFT) using B3LYP/6-311G(d), and
      the normal Raman spectrum (NRS) of BPA was assigned in detail. The surface
      enhanced Raman scattering (SERS) of the BPA molecule was obtained by gold sol
      enhancement. The adsorption of BPA to gold surface was analyzed: in acidic pH,
      the molecule was adsorbed on the gold surface by =CO-, the vibration of the band
      O-H disappeared, and the benzene ring was perpendicular on the surface of gold
      sol.

PMID- 21714249
TI  - [Sorting oleaginous yeast by using optical manipulation and Raman spectroscopy].
AB  - Extensive research has been carried out in an effort to screen the oleaginous
      microorganisms. Here, Raman spectroscopy and laser tweezers were used to sort
      oleaginous yeast from mixed yeast cells. The preprocessing of subtracted
      background, 17 points S-G smoothing filter, polynomial fitting baseline
      correction and vector normalization were performed and the main features
      information of intracellular substances from the Raman spectroscopy of yeast
      cells was extracted by combining principal component analysis. Based on the
      distinguished composition of oleaginous yeast and non-oleaginous different yeast,
      a sorting model was established. The test yeast cell in optical trapping was
      distinguished real-time by the model referring to its Raman spectra. The cells
      distinguished as oleaginous yeast were collected by means of optical
      manipulation. The sorted oleaginous yeast cells were verified by microbial
      culture and Sudan black B test. The result illustrates that Raman spectroscopy
      combined with optical manipulation is an effective technique for sorting
      oleaginous yeast and other economic microorganisms.

PMID- 21714250
TI  - [Signal analysis and spectrum distortion correction for tunable diode laser
      absorption spectroscopy system].
AB  - In the present paper, the signal of a tunable diode laser absorption spectroscopy
      (TDLAS) trace gas sensing system, which has a wavelength modulation with a wide
      range of modulation amplitudes, is studied based on Fourier analysis method.
      Theory explanation of spectrum distortion induced by laser intensity amplitude
      modulation is given. In order to rectify the spectrum distortion, a method of
      synchronous amplitude modulation suppression by a variable optical attenuator is
      proposed. To validate the method, an experimental setup is designed. Absorption
      spectrum measurement experiments on CO2 gas were carried out. The results show
      that the residual laser intensity modulation amplitude of the experimental system
      is reduced to -0.1% of its original value and the spectrum distortion improvement
      is 92% with the synchronous amplitude modulation suppression. The modulation
      amplitude of laser intensity can be effectively reduced and the spectrum
      distortion can be well corrected by using the given correction method and system.
      By using a variable optical attenuator in the TDLAS (tunable diode laser
      absorption spectroscopy) system, the dynamic range requirements of photoelectric
      detector, digital to analog converter, filters and other aspects of the TDLAS
      system are reduced. This spectrum distortion correction method can be used for
      online trace gas analyzing in process industry.

PMID- 21714251
TI  - [Interaction between ambroxol hydrochloride and human serum albumin studied by
      spectroscopic and molecular modeling methods].
AB  - In the present paper, the interaction between ambroxol hydrochloride (ABX) and
      human serum albumin (HSA) was studied under simulative physiological condition by
      spectroscopy and molecular modeling method. Stern-Volmer curvers at different
      temperatures and UV-Vis absorption spectroscopy showed that ABX quenched the
      fluorescence of HSA mainly through dynamic quenching mode. On the basis of the
      thermodynamic data, the main binding force between them is hydrophobic
      interaction. According to the theory of Forster non-radiation energy transfer,
      the binding distance between the donor and the acceptor was 3.01 nm. The effect
      of ABX on the conformation of HSA was analyzed by the synchronous and three
      dimensional fluorescence spectroscopy. Furthermore, using the molecular modeling
      method, the interaction between them was predicted from molecular angle: ABX
      might locate in the subdomain III A of HSA.

PMID- 21714252
TI  - [Wavelength intervals selection of LED illumination for color vision
      application].
AB  - In color vision application, for the images with multiple colors, object can not
      be clearly separated from complicated background. The discrimination of the
      surfaces can be enhanced by selecting appropriate wavelength intervals of
      illumination. Firstly, the reflectance functions of all the surfaces were
      calibrated by four standard references. Then partial least squares method was
      used for selecting the effective wavelength interval of illumination. The
      variables important in projection (VIP) scores of wavelength intervals were
      considered as selection criteria. Wavelength intervals with the VIP > 1.0 were
      selected for illumination. Finally, three effective wavelength intervals of LED
      illumination were selected to separate all the surfaces of experiment image
      simultaneously. For separating all the surfaces of experiment image
      simultaneously and improving discrimination, the experiment was carried out. The
      experiment results demonstrate the usefulness of this method.

PMID- 21714253
TI  - [Detection of inorganic elements in parasitic plants and their hosts].
AB  - Parasitic plants are destructive agricultural pests. Today, parasitic plants have
      been recognized as serious pests causing considerable economic damage on crop and
      woods in China. Parasites are among the most destructive weeds known, and more
      and more people begin to pay more attention to the relationship between parasitic
      plant and host. Two cistanches and their hosts were analyzed and characterized by
      ICP-AES. The contents of K, P, Na, Ca, Mg, Fe, B, Cu, Zn, Al and Mn in Tamarix
      chinensis, Haloxylon ammodendron, Cistanche deserticola and Cistanche tubulosa
      were determined. The results showed that the spectra of main elements of the two
      cistanches and their hosts are similar, but the content of each element is
      different. The content of K, P, N and Ca is higher than other element, The
      content of K and P in Cistanche deserticola and Cistanche tubulosa is higher than
      the content of theirs hosts. The present study provides a new scientific
      foundation for further study and general application of parasitic plant.

PMID- 21714254
TI  - [An adaptive VQ algorithm used in interferential multi-spectral image].
AB  - In the present paper, an adaptive LBG VQ algorithm is proposed based on the point
      to line model for the expansion of LBG VQ algorithm which was proposed in 2009,
      and using the algorithm proposed in this paper can achieve less error
      quantification, and can avoid the increase in bits of the larger index generated
      by the point to line expansion of LBG VQ algorithm. This new algorithm was used
      in lossless compression of interferential multi-spectral LASIS image, and
      experiment shows that the adaptive LBG VQ algorithm can remarkably improve the
      lossless compression performance of interferential multi-spectral image, and that
      if using these VQ algorithms above after Dual-Direction Prediction, the
      compression ratio generated by the point to line expansion of LBG VQ algorithm
      will be a little less than that generated by conventional LBG VQ algorithm, and
      the compression ratio generated by the algorithm proposed in this paper will be
      much larger than that generated by conventional LBG VQ algorithm.

PMID- 21714255
TI  - [Tree species information extraction of farmland returned to forests based on
      improved support vector machine algorithm].
AB  - The difference analysis of spectrum among tree species and the improvement of
      classification algorithm are the difficult points of extracting tree species
      information using remote sensing images, and are also the keys to improving the
      accuracy in the tree species information extraction in farmland returned to
      forests area. TM images were selected in this study, and the spectral indexes
      that could distinguish tree species information were filtered by analyzing tree
      species spectrum. Afterwards, the information of tree species was extracted using
      improved support vector machine algorithm. Although errors and confusion exist,
      this method shows satisfying results with an overall accuracy of 81.7%. The
      corresponding result of the traditional method is 72.5%. The method in this paper
      can achieve a more precise information extraction of tree species and the results
      can meet the demand of accurate monitoring and decision-making. This method is
      significant to the rapid assessment of project quality.

PMID- 21714256
TI  - [Reaction kinetics investigation of NVP in HPDLC gratings].
AB  - In order to get the HPDLC grating with high diffraction efficiency and perfect
      surface morphology, NVP was added into the reaction system of fabricating
      gratings and then the influence of NVP on the reaction kinetics of HPDLC was
      described. The analysis showed that NVP significantly increased the rate of
      polymerization in HPDLC photopolymerization, and as the highly cross-linked
      polymer network forms, the small mono-vinyl NVP appeared to react preferentially
      with double bonds inthe reaction system, facilitating additional conversion of
      pendant double bonds otherwise trapped in the polymer network. Furthermore, NVP
      also enhanced the degree of phase separation and got perfect surface morphology
      as well as higher refractive index modulation. So, the diffraction efficiency of
      HPDLC gratings was remarkably improved. However, the surface morphology and
      diffraction efficiency of HPDLC gratings would be worse when the concentration of
      NVP was too high. In a word, the addition of NVP could significantly increase the
      polymerization rate and reaction extent of reaction monomer and ultimately get
      the HPDLC grating with high diffraction efficiency (96.36%) and perfect surface
      morphology.

PMID- 21714257
TI  - [Investigation and assessment of damage in earthquake in Yushu, Qinghai based on
      multi-spectral remote sensing].
AB  - The devastating Yushu Earthquake occurred in Qinghai Province, northwest China,
      with a magnitude of 7.1 on April 14, 2010, which has caused huge destructive
      losses. Most buildings along the seismic zone were ruined, especially the old and
      the basic civil structure houses completely destroyed. The earthquake also
      triggered geological disasters, such as landslides, collapses, debris flows, etc.
      In the present study, the remote sensing technique was used to assess and analyze
      the situation of the earthquake damage. There are four classes of feature which
      can be interpreted according to the remote sensing imageries: (1) the damage
      degree of buildings, like civilian homes, temples; (2) the field disasters of
      earthquake, such as ground fissures, landslides, collapses, debris flows, and
      earthquake subsidence; (3) the damage degree of structures, such as dam; (4) the
      damage degree of the lifeline, for example, the highway. The features can be
      obtained according to high spatial resolution of remote sensing imageries,
      through image processing and interpretation methods. Post-disaster rehabilitation
      and reconstruction phase should fully consider the regional seismotectonic
      background and the carrying capacity of resources and environment. With the
      assessment results of earthquake disaster remote sensing, at last, preliminary
      suggestions were proposed for the rehabilitation and reconstruction planning of
      Yushu earthquake.

PMID- 21714258
TI  - [Influence of albumin on the spectroscopic properties and existence state of mono
      substituted phthalocyanine zinc (II)].
AB  - Interaction between 1-[4-(2-carboxyl-ethyl-)phenoxy] phthalocyanine Zinc(II)
      (ZnPcC1) and albumin (human serum albumin or bovine serum albumin) was studied.
      ZnPcC1 can be covalently bound to albumin through amide bond formation. The molar
      ratios of ZnPcC1 to albumins are found to be about 7 : 1 in the covalent
      bioconjugates. On the other hand, there are strong non-covalent interactions
      between ZnPcC1 and albumins with a binding constant of ca. 1.0 x 10(5) mol(-1) x
      L. Binding sites competition experiments suggest that the binding site locates in
      subdomain I B of human serum albumin. When conjugated to albumin, no matter
      covalent conjugation or non-covalent conjugation, the ZnPcC1 exhibit more
      distinctive characteristic monomer absorption than the free ZnPcC1, which is a
      property beneficial to photodynamic therapy. Covalent conjugation results in the
      Q-band of ZnPcC1 red-shifting about 5 nm, whereas non-covalent conjugation does
      not lead to red-shift.

PMID- 21714259
TI  - [Spectral study on the interaction of [Cu(DPPZ)(L-Ser)]+ complex with DNA and its
      analytical application].
AB  - The characteristics of resonance light scattering (RLS), UV-visible absorption
      spectra and fluorescence spectra of [Cu(DPPZ)(L-Ser)]+ with DNA were studied and
      a RLS method for the determination of DNA was established. [Cu(DPPZ) (L-Ser)]+
      could assemble on the surface of DNA through intercalation, and enhanced the RLS
      of DNA in the tris buffer of pH 7. 2. The maximum resonance light scattering peak
      appeared at 400 nm. Under the optimum conditions, the enhanced intensity of RLS
      was proportional to the concentration of DNA over the range of 0.42 - 4.2 ng x
      mL(-1), with a detection limit (3sigma/k) of 0.29 ng x mL(-1). The method was
      used for the determination of DNA samples with the recoveries between 97.8% and
      106%.

PMID- 21714260
TI  - [A cloud detection algorithm for MODIS images combining Kmeans clustering and
      multi-spectral threshold method].
AB  - An improved method for detecting cloud combining Kmeans clustering and the multi
      spectral threshold approach is described. On the basis of landmark spectrum
      analysis, MODIS data is categorized into two major types initially by Kmeans
      method. The first class includes clouds, smoke and snow, and the second class
      includes vegetation, water and land. Then a multi-spectral threshold detection is
      applied to eliminate interference such as smoke and snow for the first class. The
      method is tested with MODIS data at different time under different underlying
      surface conditions. By visual method to test the performance of the algorithm, it
      was found that the algorithm can effectively detect smaller area of cloud pixels
      and exclude the interference of underlying surface, which provides a good
      foundation for the next fire detection approach.

PMID- 21714261
TI  - [Study on saltation of fluorescence excitation spectra of erythrosine].
AB  - The fluorescence excitation spectra and absorption spectra of six kinds of
      erythrosine solutions with concentrations of 10, 20, 30, 40, 50 and 60 microg x
      mL(-1) were experimentally measured. It was found that the fluorescence
      excitation peaks are both located at 530 nm significantly when the concentrations
      of erythrosine solutions are 10 and 20 microg x mL(-1). However, the linetype
      saltation of fluorescence excitation spectrum occurs as the concentration of
      erythrosine solution is above 30 microg x mL(-1). The valley is located at 530 nm
      and two new peaks appear at both flanks of the valley. Compared with fluorescence
      excitation spectra, the absorption spectra of erythrosine solutions are without
      saltation and the peaks are all located at 530 nm. According to calculations and
      a series of contrast experiments, it was demonstrated that the absorption
      characteristic of erythrosine and the spectral measurement mode conspire to cause
      the saltation of fluorescence excitation spectra. The results can provide
      guidance for further research on physical and chemical properties of erythrosine,
      and offer help and reference for study on saltation behavior in fluorescence
      excitation spectra and improvement in spectral measuring mode.

PMID- 21714262
TI  - [Comparative investigation of molecules releasing from intra-hollow calcium
      alginate capsules using fluorimetry].
AB  - In this paper, the authors employ three different types of dye molecules, Nile
      red, Rhodamine 6G, fluorescein and a fluorescent protein-R-phycoerythrin (R-PE).
      The Rhodamine 6G is positively charged molecules, fluorescein is negatively
      charged molecules, and Nile red is neutral molecules. The R-phycoerythrins have
      either a net positive or negative charge which is balanced at the isoelectric
      point (4.22). It is negatively charged molecules also under our experimental
      condition. The Nile red, rhodamine 6G, fluorescein and R-phycoerythrin are
      trapped into alginate calcium hollow capsule respectively. The diffusion
      processes of those molecules from calcium alginate capsule to solution are
      measured based on a fluorescence method. The results indicate that electrical
      characteristics of encapsulated molecules have effect on their diffusion
      behaviors. The positively charged rhodamine 6G is well accordance with a model of
      control release from porous polymer membranes. The neutral molecules not only can
      be released from porous polymer framework, they also can directly dissolve out
      through polymer membrane. The electrostatic repulsion between fluorescein and
      negatively charged calcium alginate membranes will accelerate the molecular
      motion, which is propitious to molecules directly dissolving out through polymer
      membrane. Based on Fick's law of diffusion, R-PEs can be releases from porous
      polymer framework It shows the longest equilibrium time. Comparing neutral
      molecules, negatively and positively charge molecules show the stronger
      interaction on electric polymer membrane, which results in that the diffusion
      coefficients of rhodamine 6G and fluorescein are less than that of neutral
      molecule Nile red. The consequences obtained here should readily explain
      analogous control releasing behaviors of other functional molecules.

PMID- 21714263
TI  - [Research advances in water quality monitoring technology based on UV-Vis
      spectrum analysis].
AB  - The application of spectral analysis to water quality monitoring is an important
      developing trend in the field of modern environment monitoring technology. The
      principle and characteristic of water quality monitoring technology based on UV
      Vis spectrum analysis are briefly reviewed. And the research status and advances
      are introduced from two aspects, on-line monitoring and in-situ monitoring.
      Moreover, the existent key technical problems are put forward. Finally, the
      technology trends of multi-parameter water quality monitoring microsystem and
      microsystem networks based on microspectrometer are prospected, which has certain
      reference value for the research and development of environmental monitoring
      technology and modern scientific instrument in the authors' country.

PMID- 21714264
TI  - [Monitoring and analysis of vertical profile of atmospheric HONO, NO2 in boundary
      layer of Beijing].
AB  - Based on the scanning differential optical absorption spectroscopy (DOAS) system,
      field measurement of vertical profiles of HONO and NO2 was performed continuously
      from Aug. 27, 2007 to Sep. 4, 2007 in Chaoyang District of Beijing, and their
      vertical profiles were analyzed. Based on the acquired data, the typical vertical
      variation characteristics of HONO, NO2 and the ratio HONO/NO2 were discussed, and
      the possible formation sources of HONO were studied. The results indicated that
      the decrease of HONO with height was faster than the decrease of NO2. The study
      found good correlation between NO2 and HONO, as well as between the ratio
      HONO/NO2 and vapor, respectively. Therefore, the authors' conclusion is that HONO
      was formed by heterogeneous conversion of NO2 on surfaces or near ground and then
      transported to higher altitudes.

PMID- 21714265
TI  - [Preparation and properties of wood/modified UF prepolymer composite materials].
AB  - In the present research, the urea-formaldehyde prepolymer and multilayer hot
      press drying were used to modify poplar plantation. The prepolymer was
      impregnated into cell lumen space by pulse-dipping machine. Then the timbers were
      compressed and dried by the multilayer hot-press drying kiln. The results showed
      that the physical and chemical properties of poplar were changed in this
      investigation. The basic density of modified wood increased 1.06 times compared
      with the natural wood, and the bending strength increased 33% for modified wood,
      compressive strength parallel to grain increased 74%, the water absorption
      decreased to 97% from 104%. The crystallinity decreased slightly from 39.65 to
      36.89 because of the modifier impregnated. TGA analysis showed that the heat
      resistance of modified wood increased, the three exothermic peaks in DTA curve of
      modified wood were 280, 360 and 485 degrees C which were higher than natural wood
      in the corresponding position FTIR analysis showed that the hydroxyl modified
      material has a good association phenomenon, and carbonyl content decreased. The
      SEM spectrum showed the distribution of the prepolymer in the modified timber.

PMID- 21714266
TI  - [Effect of Fe-Mn-Si on the biomass structure of Eichhornia crassipes].
AB  - Eichhornia crassipes (water hyacinth) was cultivated under different iron (Fe),
      manganese (Mn) and silicon (Si) nutrient treatments for its biomass
      characteristics research which was determined by various items including nutrient
      element content (Fe, Mn and Si), adsorption sites and active function groups. The
      results show that Mn and Si can enhance acidic sites of the plant, in which Mn
      plays a great role, but Fe reduces the acidic sites. The sequence of acidic
      sites' amount among three parts of the plant is root > stem > leaf, in the
      treatment of Fe, Mn and their combination, and leaf > stem > root in Si
      treatment. The amount of alkaline sites is less than that of acidic sites, and
      the difference in their distributions among three parts of the plant is not
      great. Mn and Si treated Eichhornia crassipes stalks have more amorphous
      material, such as lignin, pectin and xylan (hemicellulose), which have more
      functional groups of -OH, -COOH and acidic sites.

PMID- 21714267
TI  - [Diagnosis of phosphorus nutrition in winter wheat based on first derivative
      spectra and radial basis function neural network].
AB  - The hyperspectral leaf reflectance in winter wheat was measured under 4
      phosphorus levels at different growth stages, i.e. revival stage, jointing stage,
      tassel stage and grouting stage. And their first derivative of spectra were
      calculated and denoised by the threshold denoising method based on wavelet
      transform. After studying characteristics of the two kinds of spectra resulting
      from different phosphorus contents levels as well as correlations between leaf
      phosphorus contents and spectral values, sensitive wavebands and four kinds of
      absorption areas were extracted. Then the four kinds of absorption areas and
      their corresponding leaf phosphorus content were normalized and input to RBFNN.
      Results show that: (1) Sensitive wavebands for monitoring leaf phosphorus
      contents in original leaf spectra are 426-435 and 669-680 nm. (2) Sensitive
      wavebands in first derivative of spectra are 481-493 and 685-696 nm. (3) Trained
      RBFNN can learn and seize the linearity/non-linearity mapping between samples and
      output targets.

PMID- 21714268
TI  - [Spectral property of one-dimensional rodlike nano cellulose].
AB  - The object of the present paper was researching a kind of nano cellulose prepared
      by the pretreatment of diluted acid and the physical method of high pressure
      homogenization. The cellulose pulp was pretreated by diluted acid and then
      prepared by high pressure homogenization. The one-dimensional rodlike nano
      cellulose was obtained. And the spectral properties of nano cellulose were
      characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray
      diffraction (XRD). The thermal property of nano cellulose was analyzed by
      thermogravimetric analysis (TGA). The dimension and morphology of nano celluose
      were observed using atomic force microscope (AFM) and transmission electron
      microscopy (TEM). FTIR analysis results showed that the one-dimensional rodlike
      nano cellulose had the same characteristic functional groups as cellulose pulp.
      And it was showed that intramolecular hydrogen bond association effects of nano
      cellulose were partly destroyed. It was indicated by XRD analysis that nano
      cellulose and cellulose pulp corresponded to the crystal type of cellulose I. The
      crystallinity of nano cellulose was increased from 59% to 70%, compared to
      cellulose pulp. Nano cellulose still maintained both crystalline domains and
      amorphous regions, although crystalline domains and amorphous regions were partly
      damaged by preparing process. Thermal analysis results demonstrated that the
      thermal stability of nano cellulose was lower than that of cellulose pulp. The
      decomposition temperature of nano cellulose was 330 degrees C. Two weight-loss
      stages were present in the range 292-500 degrees C. The TEM photograph showed
      that nano cellulose was significantly rodlike shape with hundreds of nanometer in
      length and tens of nanometers in width. AFM image showed that nano cellulose was
      agglomerated together.

PMID- 21714269
TI  - [Investigation of the hyperspectral image characteristics of wheat leaves under
      different stress].
AB  - The diagnosis of growing status and vigor of crops under various stresses is an
      important step in precision agriculture. Hyperspectral imaging technology has the
      advantage of providing both spectral and spatial information simultaneously, and
      has become a research hot spot. In the present study, auto-development of the
      pushbroom imaging spectrometer (PIS) was utilized to collect hyperspectral images
      of wheat leaves which suffer from shortage of nutrient, pest and disease stress.
      The hyperspectral cube was processed by the method of pixel average step by step
      to highlight the spectral characteristics, which facilitate the analysis based on
      the differences of leaves reflectance. The results showed that the hyperspectra
      of leaves from different layers can display nutrient differences, and recognize
      intuitively different stress extent by imaging figures. With the 2 nanometer
      spectral resolution and millimeter level spatial resolution of PIS, the number of
      disease spot can be qualitatively calculated when crop is infected with diseases,
      and, the area of plant disease could also be quantitatively analyzed; when crop
      suffered from pest and insect, the spectral information of leaves with single
      aphid and aphids can be detected by PIS, which provides a new means to
      quantitatively detect the aphid destroying of wheat leaf. The present study
      demonstrated that hyperspecral imaging has a great potential in quantitative and
      qualitative analysis of crop growth.

PMID- 21714270
TI  - [Spectralsignatures of nickel and vanadium supported photocatalysts and their
      photocatalytic properties].
AB  - Using SiO2, activated carbon (AC) and Al2O3 as supports, the supported
      photocatalysts Ni-V-O/SiO2, Ni-V-O/AC and Ni-V-O/Al2O3 were prepared by
      impregnation method, and their spectralsignatures were investigated. The
      carbonylation of methanol with CO2 under UV irradiation was used as a probe
      reaction to compare the photocatalytic performance of the prepared catalysts.
      Integrated with the testing results of carbonylation, the effects of different
      supports on selectivity for the carbonylation products of methyl formate (MF) and
      dimethyl carbonate (DMC) were discussed by pyridine-IR and UV-Vis techniques. XRD
      results showed that the particles of nickel and vanadium supported on SiO2 had
      the highest degree of dispersion. Results of pyridine-IR indicated that all
      catalysts retained Lewis acid sites. The acid strength was different from
      catalyst samples with different supports but with the same active components. The
      acid strengths could be arranged as follows: Ni-V-O/SiO2 > Ni-V-O/Al2 O3 > Ni-V
      O/AC. Different acid strengths exhibited different influence on the selectivity
      of products MF and DMC of carbonylation. The surface acid strengths of catalysts
      were the major factor influencing the selectivity of carbonylation products.

PMID- 21714271
TI  - [A study of non-spectral interference of iron matrix and its mechanisms in ICP
      AES analysis].
AB  - In the present paper non-spectral Interference of iron matrix whose concentration
      ranges from 0 to 5 mg x mL(-1) has been studied by using ICP-AES. And its
      mechanisms are discussed through calculating every terms of the interference
      function and investigating the relation between the values of them and Fe matrix
      concentration. The results show that in a certain concentration range (0-5 mg x
      mL(-1)) Fe matrix has no significant influence upon excitation temperature and
      electronic number density. Most of the elements' activity coefficient terms
      decreases with the increase of Fe matrix concentration. And the contribution of
      each term to the interference function is different according to atomic line and
      ionic line. It is the difference in ionization term between atomic line and ionic
      line that causes this.

PMID- 21714272
TI  - [Uncertainty evaluation of determination of copper and lead in soil by using ICP
      MS].
AB  - Copper and lead in soil samples were measured by using inductively coupled plasma
      mass spectrometry(ICP-MS), and the impacts of major source of measurement
      uncertainty were discussed. Uncertainty components such as sample weighing in the
      process of digestion, the volume size, preparation of standard solutions, curve
      fitting, measurement repeatability were analyzed and synthesized according to
      JJF1059-1999 (Evaluation and Expression of Uncertainty in Measurement), and the
      final expanded uncertainty was given. Such expression of result was more
      objective and true.

PMID- 21714273
TI  - [Determination of mineral elements in two grades of three green tea varieties by
      ICP-AES].
AB  - Green tea, a traditional healthy drink, has various necessary nutrients. A study
      was carried out on the contents of mineral elements such as Ni, Ba, Fe, Mn, Cr,
      Mg, Ca, Cu and Al in two grades of three green tea varieties by ICP-AES. The
      difference in contents of mineral elements between green teas was studied. The
      results indicated that there are different contents of mineral elements among
      varieties and grades of green tea. A basis for consumption, varieties
      identification and grades judgment was provided by the study.

PMID- 21714274
TI  - [Determination of trace determination of elements in medicinal materials of
      cultivated and wild Rhizoma et Radix Notopterygii vegetated in different months
      by flame atomic absorption spectrometry].
AB  - The contents of six trace elements Ca, Mg, Fe, Mn, Cu and Zn in the medicinal
      materials of cultivated and wild Rhizoma et Radix Notopterygii vegetated in
      different months were determined by flame atomic absorption spectrometry (FAAS)
      with air-acetylene flame, and the feature of trace elements contents and their
      seasonal dynamics were analyzed using SPSS16.0 analysis software. The recovery
      rate obtained by standard addition method ranged between 96.33% and 105.25%, and
      the relative standard deviation was 0.84%-2.98%. This showed that the method had
      good precision and definition. The study indicated that there are abundant
      microelements in medicinal materials of cultivated and wild Rhizoma et Radix
      Notopterygii. The contents of Ca are both highest in the medicinal materials of
      cultivated and wild Rhizoma et Radix Notopterygii, and the contents of Cu element
      are lowest; the contents order is Ca > Mg > Fe > Mn > Zn > Cu; the seasonal
      dynamics of Ca, Mg, Fe, Mn, Cu and Zn had obvious regularity in the medicinal
      materials of cultivated and wild Rhizoma et Radix Notopterygii. It is concluded
      that the amount of six elements in wild Rhizoma et Radix Notopterygii are more
      than the cultivated; the data can provide reference for artificial cultivation of
      wild herbs.

PMID- 21714275
TI  - [Research on the relevance of earthworms inducing soil Cd2+ absorbed by perennial
      ryegrass].
AB  - Through the method of simulating the heavy metal pollution in farmland, the
      graphite oven (GF-990) atomic absorption was used for analyzing the regulations
      of the earthworms inducing the soil Cd2+ absorbed by the perennial ryegrass. The
      result indicated: (1) under the circumstance of the soil Cd2+ density of 3-6 mg x
      kg(-1), the positive relevance appeared extremely remarkably that the contents of
      Cd2+ in underground portions of the perennial ryegrass relate to the earthworm
      quantity (r = 0.883 2-0.986 2), but in the portion above ground the positive
      relevance did not appear extremely remarkably (r = 0.345 5-0.325 4); And the
      negative relevance appeared remarkably that the contents of Cd2+ in the soil
      relate to the earthworm quantity (r = -0.588 7(-) -0.678 4). (2) Under the
      conditions of isometric number of earthworms, the more the density of Cd2+ in the
      soil, the more the increase of Cd2+ in both portions under and above ground of
      perennial ryegrass. (3) Under the same soil environment, the negative relevance
      appeared that the number of earthworms relates to the contents of Cd2+ in the
      earthworms (r = -0.982 0(-) -0.991 6).

PMID- 21714276
TI  - [Application of XRF to the analysis of Scutellaria baicalensis with space
      mutagenesis].
AB  - X-ray fluorescence spectrum (XRF) analytic method was applied to the
      determination of the contents and varieties of mineral elements in the space
      flight mutagenesis breeding scutellaria baicalensis Georgi, and compared with the
      ground group which were planted and collected together under the same conditions,
      in an attempt to search for the influence of space environment upon mutation on
      scutellaria baicalensis Georgi. The result indicates that the varieties of the
      main mineral elements in the two samples are samely basically, therefore, the two
      samples have same absorption and enrichment capability of specific element, but
      the contents of elements Ca, Na, Zn and S increase by 0.3, 0.3, 0.04 and 0.7
      times, respectively, in the space group. This modern testing method played an
      important role in the study. It is recommended that the testing method should be
      used in the selection of space bred herbal seeds for its advantages, such as
      quick, simple, highly sensitive, and of wide measure range. To conclude, New
      breeds can be selected by space breeding, it is significant for the selection and
      growing of space herbal medicine seeds, and it also has broad application in
      space breeding of medical plants.

PMID- 21714277
TI  - [Study of the phase transformation of TiO2 with in-situ XRD in different gas].
AB  - TiO2 sample was prepared by sol-gel method from chloride titanium. The phase
      transformation of the prepared TiO2 sample was studied by in-situ XRD and normal
      XRD in different gas. The experimental results showed that the phase
      transformation temperatures of TiO2 were different under in-situ or normal XRD in
      different kinds of gas. The transformation of amorphous TiO2 to anatase was
      controlled by kinetics before 500 degrees C. In-situ XRD showed that the growth
      of anatase was inhibited, but the transformation of anatase to rutile was
      accelerated under inactive nitrogen in contrast to air. Also better crystal was
      obtained under hydrogen than in argon. These all showed that external oxygen
      might accelerate the growth of TiO2, but reduced gas might partly counteract the
      negative influence of lack of external oxygen. The mechanism of phase
      transformation of TiO2 was studied by in-situ XRD in order to control the
      structure in situ.

PMID- 21714278
TI  - [Development of soft X-ray multilayer mirror at 23.4 nm].
AB  - To meet the research requirement of Ne-like Ge X-ray laser, we designed and
      fabricated soft X-ray multilayer mirrors at 23.4 nm. New material combination
      Ti/Si has been chosen based on the material selecting rule, considering the
      optical characteristics and physicochemical characteristics. Then the period
      thickness (d), material ratio (gamma), and period number (N) of the multilayer
      were optimized and the reflectivity was calculated by software. The coating
      parameters were optimized through experiments and the Ti/Si multilayer mirrors at
      23.4 nm were fabricated by magnetron sputtering coating machine. The mirrors were
      tested by X-ray diffractometer and soft X-ray reflectometer after fabrication.
      The test results of the Ti/Si multilayer were lambda0 = 23.2 nm and R = 25.8%.
      Compared with Mo/Si multiplayer, which is generally used in soft X-ray region,
      the reflectivity of Ti/Si multilayer increases 10% approximately, and FWHM
      narrows by 1.8 nm at 23.4 nm, indicating better optical performance.

PMID- 21714279
TI  - [New design of Grimm-type glow discharge source for real-time sputtered depth
      measurement].
AB  - The crater depth value of sample surface during sputtering is important analysis
      information for the depth profile analysis of glow discharge spectrometry. Real
      time sputtered depth measurement with Laser triangulation measurement method for
      glow discharge compositional analysis, effectively solves the issues of incorrect
      depth value calculation and complicated procedures in traditional depth analysis
      method. This paper presents a new Grimm-type glow discharge source for real-time
      sputtering depth measurement by laser displacement sensor. This GD source also
      ensures fine sputtering effects and ideal resolution for multi-layer structure
      and interface. Optical fiber is used to transmit glow spectrum signal from GD
      source to multi-channel photoelectric detection system. The design for the first
      time accomplishes the real-time signal collection and time-based synchronization
      analysis for both spectrum signal and sputtering depth signal. The real-time
      sputtering depth measurement curve of standard samples is obtained. The design
      and operating principle of this new-type GD-source is described in detail. Under
      the sputtering conditions of 30 mA, 900 V and 20 minutes, the sputtering rates of
      iron-based and copper-based sample sputtered by this GD source with good depth
      resolution are about 10 and 55 nm x s(-1). Surface topography picture of
      sputtering crater and microphotograph of metal samples are provided in the paper.
      Low-alloy steel standard sample is tested with this new GD source, the relative
      standard deviation (RSD) of C, Cu, Al, Ni, Mo, Mn and V elements are less than
      1.7%, while for Cr and Si elements RSDs are less than 2.6%. The result data of
      the testing is provided in this paper.

PMID- 21714280
TI  - [Selection of interpolation methods used to mitigate spectral misregistration of
      imaging spectrometers].
AB  - Spectral curvature destroys the co-registration of the spectra measured by
      dispersion imaging spectrometer. Using interpolation to re-sample the measured
      spectra at the non-offset mid-wavelengths can mitigate the spectral
      misregistration. It is very important to select an optimum interpolation method.
      The performances of six common interpolation methods are evaluated by comparing
      the residual errors in the corrected spectral radiance. The results indicate
      that, four-point cubic Lagrange interpolation and cubic spline interpolation are
      better than other four interpolation methods (linear Interpolation, three points
      quadratic polynomial interpolation, five points four-order Lagrange interpolation
      and cubic Hermite interpolation). For spectral offset of 10% deltalambda
      (deltalambda = 5 nm), the normalized errors in measured spectral radiance is PV =
      0.06, that is reduced to PV < 0.022 after interpolation with cubic Lagrange
      interpolation or cubic spline interpolation, but for other four methods they are
      PV > 0.035. Furthermore, for lower spectral resolution (deltalambda > 5 nm),
      cubic Lagrange interpolation is a little better than cubic spline interpolation;
      while for higher spectral resolution (deltalambda < 5 nm), cubic spline
      interpolation is a little better.

PMID- 21714281
TI  - [Bioelectrical activity of the myocardium in children born to parents irradiated
      during the Chernobyl disaster with isolated abnormal chords of the left
      ventricle].
AB  - A total 156 children of the main group (children born to parents irradiated
      during the Chernobyl disaster), who according to echocardiography revealed a
      different number of isolated abnormal chords of the left ventricle, 20 healthy
      children, 24 children of nosological control group and 50 children of referent
      group have been observed. It was found that isolated AHLV in children born to
      irradiated parents, was associated with changes in standard ECG, reflecting the
      presence of arrhythmias or predictors of their development. No significant
      differences in subgroups of children with different number of isolated AHLV have
      been established. Children with isolated AHLV born to parents irradiated during
      the Chernobyl accident, as all patients with minor structural anomalies of the
      heart, should be refered to a risk group in connection with the possibility of
      the development, in the first place, ventricular extrasystoles, paroxysmal
      ventricular tachycardia. Early diagnosis of isolated AHLV will allow to assess
      the outlook for further course of the disease and develop a plan of treatment and
      preventive measures.

PMID- 21714282
TI  - [Metabolism of polyunsaturated fatty acids and its value for a human body].
AB  - The article is devoted to the study of metabolism of polynonsaturated fat acids
      in a human body as antiatherogenous which prevents the development of
      cardiovascular diseases (ischemic heart disease, hypertension), as well as
      oncological diseases, a peptic ulcer of the stomach and duodenum.

PMID- 21714283
TI  - [Predictors of cognitive impairment in patients with essential hypertension].
AB  - Clinical, instrumental, laboratory and neuropsychological examinations were
      performed in 79 patients with essential hypertension (EH). It was found using
      multiple linear regression analysis that significant predictors of cerebral
      disorders in patients with EH are elevated maximum values of systolic blood
      pressure (BP) according anamnesis data, increased intima-media thickness,
      increased mean daytime diastolic BP load values, increased average daytime mean
      BP values, increased maximum 24-hours mean BP values, increased pulse pressure
      variability by ambulatory BP monitoring, elevated levels of total cholesterol, a
      lower educational level, a greater age of patients and worsening of subjective
      stress assessment.

PMID- 21714284
TI  - [Coronary reserve peculiarities in patients with ischemic heart diseases
      depending on gender and age aspects].
AB  - Results of clinical and functional studies of 183 patients with organic patology
      of the cardiovascular system are presented in the article. Coronary reserve
      peculiarities in women were determined depending on their age. The analysis of
      dynamics of quantity indicators of myocardium ischemia at hospitalization has
      shown that patients aged till 45 years have sexual dependence of distribution of
      changes of repolarization phase, patients older age group it is not so
      determined. During carrying out of loading tests the percent of the reached
      loading decreased with age increase, considerably conceding in women,
      quantitative changes of myocardium ischemia increased with age with an
      insignificant prevalence in men. Positive test was observed with maximum
      frequency in patients with ischemic heart disease (IHD). The analysis of
      haemodynamic shifts in patients with organic diseases has shown that similar
      changes correlated with a stable tendency to decrease in fraction of ejection
      fraction.

PMID- 21714285
TI  - [Hemocoagulation disorders in patients with acute pancreatitis].
AB  - 62 patients with acute pancreatitis (AP) were examined in order to determine
      hemocoagulation disorders. The obtained results showed that the patients
      developed the consumptive coagulopathy with high levels of D-dimer, activation
      and exhaustion of antithrombin III (AT III). The development of hemocoagulation
      disturbances in patients with severe AP was confirmed through decrease of
      activity of AT III up to 68% and high level of D-dimer>693 ng/ml.

PMID- 21714286
TI  - [Kidney lesions in a diphtheria catamnesis].
AB  - 150 persons aged from 16 to 65 years found in a diphtheria catamnesis have been
      observed. Clinical and laboratory as well as ultrasonic signs of kidney lesions
      in an acute period of a pharynx diphtheria have been studied. These signs
      corresponded to tubulo-interstitial nephritis. Obtained data testifies that more
      severe old form of diphtheria in the acute period is more often symptoms of
      kidneys lesion in a catamnesis period are revealed and they remain throughout
      long time. 47.5% of patients in a diphtheria catamnesis had clinical-laboratory
      and echographic signs of kidneys lesion, 81.3% of them clinically presented pain
      and edematic syndromes, uropoiesis and urine passage disturbances; depression of
      renal functions (concentration and depurination), an urinary syndrome;
      sonographic signs of kidneys lesion were observed and manifested at maximum level
      1-3 years after an acute period of a pharynx diphtheria. Perimedullary thickness
      was revealed in 20-45% of patients depending on severity of the disease, it was
      combined with single and multiple calcifications and a calcification of pyramids
      papillas. According to ultrasonic data, the nephrocalcinosis has been found 1.2
      times oftener after average degree of severity and 2 times oftener after severe
      degree of severity of pharynx diphtheria in comparison with mild form of the
      disease. The calcification of papillas of the pyramids, found out in a diphtheria
      catamnesis, had been developed in a place of necrosis of papillas of pyramids in
      patients in an acute period of disease.

PMID- 21714287
TI  - [Clinical and diagnostic characteristics of the fatty acid spectrum of lipids in
      patients with generalized periodontitis].
AB  - A comparative analysis of complex survey of 67 patients with generalized
      periodontitis was carried out. In comparing different biological diagnostic
      media: in the peripheral blood (plasma and red blood cells), in the leachate
      content of periodontal pockets (PP) and a secret glandula Parotis, determined
      unidirectional imbalance of fatty acid spectrum (FA) due to excessive
      accumulation of saturated (LCD, NLC) and reduction in an amount of unsaturated
      (UFA) and polyunsaturated (PUFA) was defined, regardless of the disease course.
      Differential diagnostic and prognostic test in complex study of LCD spectrum is
      an excess oxidation of arachidonic acid (AA) in PP and plasma levels on the
      background of the identified imbalance, with significant reduction in
      accumulation of AK by 25% in erythrocyte membranes and the filtrate PC, which
      characterizes the change in plasticity and permeability of cell membranes, which
      affects their functional activity.

PMID- 21714288
TI  - [Changes of the endothelial function and cardiac valves in patients with reactive
      arthritis].
AB  - Our investigations showed endothelium's malfunction and changes of the cardiac
      valves in patients with reactive arthritis, which could be precondition of the
      cardiac failure development in these patients.

PMID- 21714289
TI  - [Application of pneumothermometric index for respiratory thermoregulation
      assessment in patients with ischemic heart disease].
AB  - We enrolled 153 patients with Ischemic Heart Disease admitted to general
      hospital: 33--with aterosclerotic cardiosclerosis, 70--with acute myocardial
      infarction (AMI), 17--with postinfarctial cardiosclerosis, 33--with unstable
      angina. 30 control subjects (middle aged men and women) were recruited. Exhaled
      breath temperature (Te), ambient temperature (Tam) and axillaris temperature
      (Tax) were measured. The predicted expired air temperature (prTe) and three
      pneumothermometric indexes were calculated: index ThetaEAT-(Te-Tam)/(prTe-Tam);
      index DeltaEAT-(Tax-Te)/(Tax-prTe); index lamdaEAT-(Te-predTe)/(Te-predTe). Index
      DeltaEAT is the most effective index for revealing disorders of respiratory heat
      exchange in myocardial infarction. Index lamdaEAT is the most effective
      pneumothermic one for revealing disorders of respiratory heat exchange in
      aterosclerotic cardiosclerosis.

PMID- 21714290
TI  - [Efficacy of short-term metformin application in complex treatment of patients
      with coronary artery disease and concomitant metabolic syndrome].
AB  - The inclusion of a short course of metformin in complex therapy of coronary
      artery disease with metabolic syndrome does not alter the clinical features of
      disease. It had a positive effect on weight loss and the activity of systemic
      inflammation. The lipid metabolism and insulin resistance were not significantly
      altered. This results suggest that the treatment with metformin during 1 month in
      patients with coronary artery disease and metabolic syndrome is sufficient for
      the manifestation of systemic anti-inflammatory effect of the drug, but not
      enough to implement a reliable effect of insulin resistance and to improve the
      clinical features of coronary artery disease.

PMID- 21714291
TI  - [Application of Bifi-forma in a complex treatment of children of the early age
      with non-hospital pneumonia].
AB  - The majority of patients with non-hospital pneumonia (NHP) on background of
      antibioticotherapy had changes of a microbiocenosis of their intestines. The
      article presents obtained results on the assessment of Bifi-forma probiotic use
      for 63 children aged from 1 month till 3 years. It has been shown that course of
      the pneumonia has been associated clinically with dyspepsic pain syndromes and
      with significant changes of intestine biocenosis by quantity reduction of bifido-
      and lactobacteria, decrease in escherichia having enzymatic activity and increase
      in hemolytic escherichia, yeastlike mushrooms, staphylococcus and other
      representatives of opportunistic flora. Application of this probiotic in a
      complex therapy on non-hospital pneumonia has shown high clinical and
      microbiological efficiency that allows recommending its administration to
      children of early age, patients with non-hospital pneumonia.

PMID- 21714292
TI  - [Efficacy of complex therapy with metformin and ramipril combination for patients
      with metabolic syndrome].
AB  - We have studied efficiency of a complex therapy with metformin and ramipril
      combination (1000 mg and 5 mg per day) respectively in patients with metabolic
      syndrome (MS). The group of patients with MS which answered the basic criteria
      IDF (2005) was determined. Carbohydrate and Lipidic metabolism were studied.
      Patients were characterized with raised weight index (WI), arterial hypertension,
      increased concentration of triglycerides in blood serum, of glucose, of HbAlc
      level and S-peptide, and also high level of endotelin (1-38) and
      CD32+CD40+circulating particles of endothelium. Three months treatment lead to
      decrease in WI, arterial pressure, triglycerides concentration, HbAlc, glucose,
      except CD32+CD40+. Six months treatment lead to more expressed positive dynamics.
      Thus, metformin and ramipril combination in patients with MS leads to decrease in
      insulin resistancy, carbohydrate and lipid metabolism normalization, to
      restoration of endothelium functions that is possible to consider as prophylaxis
      of the development of type 2 diabetes melitus and its cardiovascular
      complications.

PMID- 21714293
TI  - [New approaches to neuro-metabolic pharmacotherapy of discirculatory
      encephalopathy].
AB  - Modern view on pathogenesis and clinics of one of the most important forms of
      chronic cerebrovascular insufficiency--discirculatory encephalopathy has been
      presented in this article. The author has analyzed requirements to optimal
      treatment choice of this pathology. Action mechanisms and peculiarities of
      clinical use of Vasonat medication were detailed. This medication with good
      clinical and pharmacological properties allows to realize the strategy of
      pathogenetically proved neuromethabolical pharmacotherapy in angioneurology.
      Clinical advantage of Vasonat, its safety characteristics, and recommendations of
      practical use have been detailed.

PMID- 21714294
TI  - [Main sonographic parameters of regional anesthesia conduction in the lower
      extremities under ultrasound guidance].
AB  - The purpose of this research is to study the main sonographic parameters of nerve
      and needles, as well as some methodological aspects of regional anesthesia under
      ultrasound control, comparing the results of different methods, approaches to the
      performance of lower limbs regional anesthesia under ultrasound guidance, the
      formulation of general principles for optimization of visual identification of
      the needle, catheter during anesthesia with the definition of localization,
      structure and distribution of entered anesthetic. The ultrasound is an effective
      method of control of the lower extremities regional anesthesia. The further study
      and improvement of methodological aspects is required. With the proposed method
      is possible to conduct qualitative sonographic navigation with high efficiency in
      all patients.

PMID- 21714295
TI  - [Comparative study of quality of life in patients with psoriasis from Lithuania
      and Ukraine].
AB  - Lithuania and Ukraine have different models of national health care. We decided
      to determine whether difference in health care systems influence quality of life
      (QoL) of psoriasis patients from Lithuania and Ukraine. Lithuanian and Ukrainian
      versions of the Dermatology Life Quality Index (DLQI) and Skindex-16 were used.
      157 Lithuanian and 136 Ukrainian in-patients with chronic plaque psoriasis were
      invited to complete questionnaires. The distribution of each separate item
      according its influence on QoL was the same for Lithuanian and Ukrainian
      psoriatic patients. Lithuanian patients had higher overall mean score for the
      DLQI (P<0.05) and Skindex-16 (P<0.001). Significantly higher number of Ukrainian
      psoriatic patients showed no or small effect on their life (P<0.001) and
      significantly higher number of Lithuanian psoriatic patients had very large or
      extremely large effect on their life according to the DLQI (P<0.05). The number
      of psoriatic patients with a moderate effect on their life according to the DLQI
      did not differ significantly between patients from both countries. We found
      almost equal distribution of QoL domains assessed by Lithuanian and Ukrainian
      psoriatic patients. Differences in QoL assessment by Lithuanian and Ukrainian
      psoriatic patients may be attributed to peculiarities of health care systems and
      cross-cultural inequivalence.

PMID- 21714296
TI  - [Forecasting of medication costs for elderly patients during in-hospital
      treatment stage].
AB  - Based on data analysis concerning the character and the frequency of diseases as
      well as medication therapy costs, there has been developed a functional model of
      the provision of needs in costs on medication aid for elderly and advanced old
      people in patient care institutions. This model allows take into account age
      peculiarities of the patients (polymorbidity, disease severity, regional
      differences in the character of pathology).

PMID- 21714297
TI  - [Dynamic method of trauma prophylaxis during mass sport exercises].
AB  - This article is dedicated to the original technique of prophylactics of sport
      injuries during mass sport exercises, especially in time of overcoming physical
      obstacle exercises. The results of the study showed that preliminary application
      of specially designed training program aimed at improving movement coordination,
      strengthening responsible muscle groups which are responsible quality of
      exercises to be completed allows decreasing the level of sport injuries during
      mass sport exercises among young sportpeople, especially in time of overcoming
      different physical obstacle exercises.

PMID- 21714298
TI  - [Nikolai Ivanovich Pirogov--surgeon, scientist, teacher and public figure].
AB  - The article presents data on the outstanding surgeon and scientist, the teacher
      and public figure. Its contribution to the development of surgical anatomy and
      anatomo-experimental direction of surgery, field medical surgery, the
      organization and tactics of medical maintenance of armies are discussed.

PMID- 21714299
TI  - [V. Ia. Dzhunkovskii--the first historian of the national medicine].
AB  - The article is devoted to the life and work of Vasily Yakovlevich Dzhunkovsky-
      the forgotten first historian of the national medicine.

PMID- 21714300
TI  - Osteopathic Issues Raised by the September 2010 JAOA.

PMID- 21714301
TI  - [A 62-year old man presenting with sudden-onset left hemiplegia, headache, and
      fecal incontinence with early CT signs of acute right middle cerebral artery
      infarction and right internal carotid occlusion].

PMID- 21714302
TI  - National Collegiate Athletic Association Injury Surveillance System commentaries:
      introduction and methods.
AB  - OBJECTIVE: To describe the history and methods of the National Collegiate
      Athletic Association (NCAA) Injury Surveillance System (ISS) as a complement to
      the sport-specific chapters that follow. BACKGROUND: The NCAA has maintained the
      ISS for intercollegiate athletics since 1982. The primary goal of the ISS is to
      collect injury and exposure data from a representative sample of NCAA
      institutions in a variety of sports. Relevant data are then shared with the
      appropriate NCAA sport and policy committees to provide a foundation for evidence
      based decision making with regard to health and safety issues. DESCRIPTION: The
      ISS monitors formal team activities, numbers of participants, and associated time
      loss athletic injuries from the first day of formal preseason practice to the
      final postseason contest for 16 collegiate sports. In this special issue of the
      Journal of Athletic Training, injury information in 15 collegiate sports from the
      period covering 1988-1989 to 2003-2004 is evaluated. CONCLUSIONS: Athletic
      trainers and the NCAA have collaborated for 25 years through the NCAA ISS to
      create the largest ongoing collegiate sports injury database in the world. Data
      collection through the ISS, followed by annual review via the NCAA sport rules
      and sports medicine committee structure, isa unique mechanism that has led to
      significant advances in health and safety policy within and beyond college
      athletics.The publication of this special issue and the evolution of an expanded
      Web-based ISS enhance the opportunity to apply the health and safety decision
      making process at the level of the individual athletic trainer and institution.

PMID- 21714303
TI  - [One hundred books which built up neurology (53)--Emil Heinrich du Bois-Reymond
      "Untersuchungen Uber thierische Elektricitat" (1848-1849)].

PMID- 21714304
TI  - Parent's kiss: successful removal of a nasal bauble.

PMID- 21714305
TI  - Knee dislocation in touch rugby: a case study.

PMID- 21714306
TI  - Lost days--diaries for military intensive care patients.
AB  - There is a real possibility of critically injured service personnel suffering
      from psychological disturbance as a result of not being able to recall traumatic
      events. Many patients report symptoms of depression, anxiety and other
      psychological disturbances such as hallucinations, delusional memories and
      nightmares after discharge from an Intensive Care Unit (ICU). Patients who have
      memories of ICU, sometimes unpleasant ones, as opposed to those who have no
      memories of their stay in ICU, suffer less anxiety, panic attacks and other PTSD
      related symptoms. The impact for clinical practice is that, whilst health care
      professionals cannot remove all of the stressors of treatment in ICU for service
      personnel, we must try to minimise their impact by providing continued patient
      information and reassurance. The introduction of patient diaries has helped this
      vulnerable group of patients and the feedback from patients and their relatives
      validates this. Patient diaries have been developed and introduced for use by
      military patients and further exploration of their impact expected.

PMID- 21714307
TI  - SALIVA--a forgotten fluid.

PMID- 21714308
TI  - Sailing new waters--Role Two Afloat medical facility. Enhanced counter piracy
      operations September-December 2010.

PMID- 21714309
TI  - HMS York--OP deference.

PMID- 21714310
TI  - Journey of a book.

PMID- 21714311
TI  - "F" for public policy.

PMID- 21714312
TI  - Canadians continue to consume too much sodium and not enough potassium.
AB  - OBJECTIVES: Excessive sodium (Na) intakes and insufficient potassium (K) intakes
      are known contributors to hypertension. In July 2010, the Health Canada-led multi
      stakeholder Sodium Working Group issued recommendations to lower Na intakes of
      Canadians. Baseline data and ongoing monitoring are needed. METHODS: Na and K
      content based on recently analyzed food composite samples from the Canadian
      marketplace were matched with over 35,000 dietary recalls from the Canadian
      Community Health Survey (CCHS 2.2). The distributions of usual intakes for Na and
      K were constructed using SIDE software and estimates by age and sex for the 5th,
      10th, 25th, mean, median, 75th, 90th and 95th percentiles were determined.
      RESULTS: Based on recent analyses of Canadian foods, the majority of Canadians
      exceeded the Tolerable Upper Intake Level (UL) for Na for their age and sex
      group, including infants, children, adolescents and adults. In sharp contrast,
      few had Adequate Intakes (AI) of K. CONCLUSION: Canadians of all ages need to
      decrease Na intakes below the UL. At the same time, increased consumption of
      dairy products, fruits and vegetables must be promoted to increase K intakes to
      current recommendations. Both dietary interventions are required to help lower
      hypertension in the Canadian population. We provide the first report based on
      direct analysts of Canadian foods, confirming the high Na and low K intakes of
      the Canadian population. With its annual sampling program of foods commonly
      consumed in Canada, the Total Diet Study provides an important sentinel system
      for monitoring these dietary risk factors for hypertension.

PMID- 21714313
TI  - Occupational physical activity and body mass index (BMI) among Canadian adults:
      does physical activity at work help to explain the socio-economic patterning of
      body weight?
AB  - BACKGROUND: The behavioural and socio-cultural processes underlying the
      association between socio-economic position (SEP) and body mass index (BMI)
      remain unclear. Occupational physical activity (OPA) is one plausible explanatory
      variable that has not been previously considered. OBJECTIVES: 1) To examine the
      association between OPA and BMI, and 2) to examine whether OPA mediates the SEP
      BMI association, in a Canadian population-based sample. METHODS: This cross
      sectional study was based on secondary analysis of the 2008 Canadian Community
      Health Survey data, focusing on adults (age 25-64) working at a job or business
      (men, n = 1,036; women, n = 936). BMI was based on measured height and weight and
      we derived a novel indicator of OPA from the National Occupational Classification
      Career Handbook. Our analytic technique was ordinary least squares regression,
      adjusting for a range of socio-demographic, health and behavioural covariates.
      RESULTS: OPA was marginally associated with BMI in women, such that women with
      medium levels of OPA tended to be lighter than women with low levels of OPA, in
      adjusted models. No associations between OPA and BMI were detected for males.
      Baron and Kenny's (1986) three conditions for testing mediation were not
      satisfied, and thus we were unable to proceed with testing OPA as a mediator.
      CONCLUSIONS: Notwithstanding the small effects observed in women, overall the
      associations between OPA and BMI were neither clear nor strong, which could
      reflect conceptual and/or methodological reasons. Future research on this topic
      might incorporate other plausible explanatory variables (e.g., job-related
      psychosocial stress) and adopt a prospective design.

PMID- 21714314
TI  - Importance of frequency, intensity, time and type (FITT) in physical activity
      assessment for epidemiological research.
AB  - Physical activity is a multi-faceted behaviour comprised of several components:
      frequency, intensity, time and type (FITT). Despite this understanding, there is
      currently a lack of knowledge regarding how the individual components of FITT
      influence chronic diseases. This is partly due to the tendency for researchers to
      focus on intensity via obtaining accurate measurements of energy expenditure.
      Although energy expenditure is an important consideration in the assessment of
      physical activity, it is only one component. Accordingly, future studies
      examining the association between physical activity and disease risk would
      benefit from examining all the components of FITT. Considering that all the
      components of FITT are modifiable, knowing their independent or combined
      influence on risk may provide valuable insight for future prevention
      interventions.

PMID- 21714315
TI  - Neighbourhood environmental correlates of perceived park proximity in Montreal.
AB  - OBJECTIVES: Perceived proximity to recreational settings has been shown to be
      associated with increased physical activity levels. We examined individual socio
      demographic and environmental correlates of perceived park proximity in Montreal
      to assess targets for ecological interventions to improve physical activity.
      METHODS: A stratified clustered sampling design was used to collect data on
      perceived park proximity from 864 adults residing in 300 Montreal census tracts.
      Perceived park proximity was measured by asking participants if they perceived a
      park as within walking distance of their home. Objective measures of park
      proximity and park density were constructed using geographic information systems
      (GIS). Canada Census data provided information on census tract population density
      and median income levels. Multilevel logistic regression was used to examine the
      likelihood of not perceiving a park as proximate. RESULTS: Older adults were more
      likely to perceive a park as not proximate to their home (OR: 1.04; 95% CI: 1.02
      1.07). Perceived park proximity varied across Montreal neighbourhoods with an
      interclass correlation coefficient of 16.10%. Objective distance to the closest
      park (OR: 1.45; 95% CI: 1.10-1.92) was associated with adults' subjective
      perceptions of park proximity. Residents of neighbourhoods with higher population
      density (OR: 0.92; 95% CI: 0.87-0.97) and higher average income (OR: 0.45; 95%
      CI: 0.24-0.87) were less likely to view a park as outside walking distance to
      their residence. CONCLUSION: Regardless of the actual distance to the park,
      neighbourhood environmental factors are associated with people's perceptions of
      having a park within walking distance of their homes.

PMID- 21714316
TI  - Do crack smoking practices change with the introduction of safer crack kits?
AB  - OBJECTIVES: Crack smoking has increased in Vancouver despite the harms associated
      with its use. Many people who smoke crack share their equipment, thereby
      increasing their risk for infectious disease. This project explored the effects
      of outreach distribution of "safer crack kits" on smoking practices. METHODS: Two
      cross-sectional surveys were conducted, the first prior to kit distribution and
      the second a year later. Participants were individuals who smoked crack and lived
      in Vancouver's inner city. Crack smoking practices and use of items in the crack
      kit were documented. RESULTS: The results of the second survey (i.e., following
      12 months of kit distribution) showed an increase in availability and use of
      safer use items; mouthpieces and condoms provided in the kit were used by 79% and
      59% of recipients, respectively. Unsafe practices were reported post
      distribution: although 42% used brass screens, the majority reported that they
      usually used Brillo; over 40% of respondents reported using syringe plungers to
      scrape crack resin; and participants reported sharing crack-use paraphernalia.
      CONCLUSION: While kit distribution made safer use items more accessible, its
      impact on safer use practice was limited. Our findings highlight the need for
      targeted distribution of safer use items. Future research should explore the
      dynamics of unsafe crack smoking practices and ways to leverage safer use
      messaging.

PMID- 21714317
TI  - Optimizing Canadian public immunization programs: a prescription for action.
AB  - Recent expansion of public vaccination programs for children and youth offers new
      health benefits but at substantially increased cost. As with other large public
      investments, immunization programs ought to be systematically evaluated for
      safety, effectiveness and economic value. At present, program evaluations are
      suboptimal in most provinces and territories. Experts in public health and
      vaccinology who attended a workshop in 2009 reviewed the shortcomings and
      produced "prescriptions for action" to improve matters. Six key recommendations
      were made: 1) a formal requirement should exist to evaluate all public
      vaccination programs appropriately; 2) greater voluntary harmonization of
      programs will facilitate evaluations; 3) a mechanism is needed to prioritize and
      coordinate program-specific evaluations; 4) new funding mechanisms are needed for
      basic jurisdictional studies and joint studies of broad relevance; 5) strong
      emphasis is needed on capacity development and training; and 6) administrative
      barriers to accessing health information systems and publishing evaluation
      studies need to be overcome. The expert group considered the need to improve
      program evaluations as urgent and compelling, with success achievable with
      dedicated funding and effective leadership. Demonstrating that Canadian
      immunization programs are among the world's best and safest is a sound strategy
      for maintaining public participation in those programs.

PMID- 21714318
TI  - Administration of the adjuvanted pH1N1 vaccine in egg-allergic children at high
      risk for influenza A/H1N1 disease.
AB  - BACKGROUND: In Canada, the pH1N1 influenza vaccine is recommended for children,
      particularly those less than 5 years of age or with chronic underlying disease.
      The pH1N1 vaccine, which contains residual allergenic egg white proteins, may
      pose a risk for vaccination of egg-allergic children. OBJECTIVE: To describe the
      outcome of pH1N1 influenza vaccine administration to egg-allergic children at
      risk for severe H1N1 disease. DESIGN/METHOD: Prospective observational cohort
      study. Children identified as at high risk for egg allergy and H1N1 influenza
      were vaccinated using a two-dose split protocol in a controlled medical setting.
      Children were given an initial test dose; if no reaction was noted, the remainder
      of the dose was administered and the children were followed for allergic
      reactions. Those who tolerated the split dose and required a second dose of
      vaccine were offered vaccination four weeks later as one injection. RESULTS:
      Sixty-two egg-allergic children considered at high risk for H1N1 disease received
      the adjuvanted pH1N1 vaccine. Egg allergy was diagnosed both clinically by an
      allergist and using skin and/or serum IgE testing. Within one hour of
      immunization, 2 children developed hives, 1 had a vasovagal response and 1 had a
      hypo-responsive episode. Fourteen children received the second H1N1 dose and 1
      developed erythema and itching. There were no anaphylactic reactions. CONCLUSION:
      Administration of the adjuvanted pH1N1 vaccine in egg-allergic children at risk
      for severe H1N1 influenza was safe when performed in a two-dose split protocol in
      a controlled medical setting.

PMID- 21714319
TI  - Canadian newspaper coverage of the A/H1N1 vaccine program.
AB  - OBJECTIVES: The A/H1N1 mass vaccination program in Canada garnered considerable
      attention from the media, including extensive newspaper coverage. Media reports
      have been shown to influence the public's health care decisions, including
      vaccination choices. We analyzed Canadian newspapers' portrayal of the A/H1N1
      vaccine including mention of risks and benefits of the vaccine and whether the
      article supported, questioned or was neutral about the vaccine. METHODS: We
      compiled a data set of Canadian newspaper articles (N = 234) and conducted a
      frequency content analysis to examine discussion and/or mention of evidence
      concerning vaccination, risks of the A/H1N1 virus and the vaccine, and tone of
      article in regards to the vaccination program in Canada. RESULTS: Reasons for
      getting vaccinated appeared in 71.8% of the articles, whereas only 18.4% provided
      reasons against getting vaccinated. Discussion of evidence to support claims for
      or against getting vaccinated appeared in only 27.8% and 6.8% of the articles,
      respectively. Risks associated with contracting the A/H1N1 virus were discussed
      in 49.6% of the articles and risks of the A/H1N1 vaccine were discussed in 12.4%
      of the articles. CONCLUSION: Newspaper coverage in Canada was largely supportive
      of the A/H1N1 mass vaccination program. However, serious risks associated with
      contracting the A/H1N1 virus were also frequently discussed in the print media.
      The news articles rarely presented direct evidence to support statements that the
      vaccine was safe, effective and properly tested. Known risks (such as potential
      allergic reactions and flu-like side effects) of the vaccine were rarely
      reported. The relationship between media portrayals and vaccine uptake warrants
      further research.

PMID- 21714320
TI  - Why are some settings resource-poor and others not? The global marketplace,
      perfect economic storms, and the right to health.
AB  - Analyses of how health system priorities should be set in resource-poor settings
      are routine in the health ethics and policy analysis literature. Less attention
      is devoted to asking why some settings are resource-poor and others not. Asking
      this question must be considered a central task of global health research.
      Comparison of the relatively meager resources devoted to improving the health of
      the poor with the sums routinely mobilized for other purposes serves as a basis
      for ethical reflection and a route into necessary questioning of power imbalances
      in the world economy. The 2008 financial crisis and related developments
      underscore the urgency of such questioning, and the value of research and
      advocacy collaborations (for example, between the human rights and public health
      research and practice communities) focused specifically on the destructive
      consequences of the global marketplace for health.

PMID- 21714321
TI  - Making the case for human rights in global health education, research and policy.
AB  - If the 2010 CPHA conference is a bellwether of mainstream Canadian public and
      global health practice, its dearth of human rights papers suggests that, outside
      a small scholarly cohort, human rights remain marginal therein. This potential
      'rights gap' conflicts with growing recognition of the relationship between
      health and human rights and ergo, the importance of human rights education for
      health professionals. This gap not only places Canadian health research outside
      the growing vanguard of academic research on health and human rights, but also
      ignores a potentially influential tool for achieving health equity. I suggest
      that human rights make a distinctive contribution to such efforts not replicated
      within other social justice and equity approaches, making human rights education
      a crucial complement to other ethical training. These contributions are evident
      in the normative specificity of the right to health in international law and its
      legally binding nature, in the success of litigation, the successful advocacy for
      AIDS treatment and the growing adoption of rights-based approaches to health.
      Canadian academic and research institutions should take up their rightful place
      within health and human rights research, education and practice globally,
      including by ramping up human rights-oriented education for health professionals
      within Canadian universities.

PMID- 21714322
TI  - Inequalities in determinants of health among Aboriginal and Caucasian persons
      living with HIV/AIDS in Ontario: results from the Positive Spaces, Healthy Places
      Study.
AB  - OBJECTIVES: Aboriginal Canadians (i.e., First Nations, Inuit and Metis) are
      disproportionately affected by HIV/AIDS, and experience greater social and
      economic marginalization and poorer housing conditions. This study sought to
      understand the differences in the determinants of health and housing-related
      characteristics between samples of Aboriginal and Caucasian adults living with
      HIV/AIDS in Ontario. METHODS: We analyzed baseline demographic, socio-economic,
      health, and housing-related data from 521 individuals (79 Aboriginal and 442
      Caucasian) living with HIV/AIDS and enrolled in the Positive Spaces, Healthy
      Places study. We compared the characteristics of Aboriginal and Caucasian
      participants to identify determinants of health and housing-related
      characteristics independently associated with Aboriginal ethnicity. RESULTS:
      Compared to Caucausian participants living with HIV, Aboriginal participants were
      more likely to be younger, female or transgender women, less educated,
      unemployed, and homeless or unstably housed. They were also more likely to have
      low incomes and to have experienced housing-related discrimination. In a
      multivariate model, gender, income, and experiences of homelessness were
      independently associated with Aboriginal ethnicity. CONCLUSION: Aboriginal
      individuals living with HIV/AIDS in our sample are coping with significantly
      worse social and economic conditions and are more likely to experience
      challenging housing situations than a comparison group of Caucasian individuals
      living with HIV/AIDS. To develop effective care, treatment and support strategies
      for Aboriginal peoples with HIV, it is critical to address and improve their
      socio-economic and housing conditions.

PMID- 21714323
TI  - Prevalence and predictors of urethral chlamydia and gonorrhea infection in male
      inmates in an Ontario correctional facility.
AB  - OBJECTIVES: To determine the prevalence of urethral chlamydia and gonorrhea in
      males in a correctional facility in Ontario, Canada, and to explore risk factors
      for infection. METHODS: Between June and December, 2009, 500 adult males who had
      been newly admitted at a correctional facility in southern Ontario completed a
      survey of risk factors and provided a urine sample for testing. Those who tested
      positive were treated and their names were provided to the local public health
      unit for follow-up including contact tracing. Prevalence and 95% confidence
      intervals were calculated for infection with chlamydia and gonorrhea,
      respectively, and a multivariable model was used to look at risk factors for
      infection. RESULTS: The study population reported high levels of sexual risk
      behaviours and drug use. The overall chlamydia prevalence was 2.9% (95% CI 1.6
      4.8) and the overall gonorrhea prevalence was 0.6% (95% CI 0.1-1.8). Rates were
      particularly high for chlamydia in younger males, at 16% (95% CI 4.5-36) in 18-19
      year olds and 3.7% (95% CI 1.0-9.3) in 20-24 year olds, and for gonorrhea in
      males aged 20-24 at 1.9% (95% CI 0.2-6.6). A multivariable logistic regression
      model revealed that though not statistically significant, younger age was
      associated with infection. CONCLUSION: The relatively high prevalence of
      chlamydia and gonorrhea found in this study suggests that primary and secondary
      prevention programs should be instituted for males in correctional facilities, in
      particular among younger inmates. Further research is required to ensure internal
      and external generalizability of these results, as well as to determine the cost
      effectiveness of potential interventions.

PMID- 21714324
TI  - Using centralized laboratory data to monitor trends in herpes simplex virus type
      1 and 2 infection in British Columbia and the changing etiology of genital
      herpes.
AB  - OBJECTIVES: Understanding the regional epidemiology of genital Herpes Simplex
      Virus (HSV) infections is important for clinical and public health practice, due
      to the increasing availability of type-specific serologic testing in Canada and
      the contribution of genital HSV-2 infection to ongoing HIV transmission. We used
      centralized laboratory data to describe trends in viral identifications of
      genital HSV in BC and assess the utility of these data for ongoing population
      surveillance. METHODS: Records of viral identifications (1997-2005) were
      extracted from the Provincial Public Health Microbiology & Reference Laboratory
      database. Classification as genital or other site was based on documented
      specimen site. We conducted a descriptive analysis of trends over time, and
      calculated odds of HSV-1 infection among individuals with genital herpes.
      RESULTS: Of 48,183 viral identifications, 56.8% were genital, 10.0% were peri
      oral and 9.1% cutaneous; site was unknown for 22.9%. Among genital
      identifications, HSV-1 infection was more likely in females, younger age groups,
      and later time periods. The proportion of genital herpes due to HSV-1 increased
      over time from 31.4% to 42.8% in BC. CONCLUSIONS: Our analysis of population
      level laboratory data demonstrates that the proportion of genital herpes due to
      HSV-1 is increasing over time in BC, particularly among women and younger age
      groups; this has implications for clinical practice including the interpretation
      of type-specific serology. Provincial viral identification data are useful for
      monitoring the distribution of genital HSV-1 and HSV-2 infections over time.
      Improving clinical documentation of specimen site would improve the utility of
      these data.

PMID- 21714325
TI  - 'Before you teach me, I cannot know': immigrant women's barriers and enablers
      with regard to cervical cancer screening among different ethnolinguistic groups
      in Canada.
AB  - OBJECTIVE: To describe the similarities and differences among multiple groups of
      immigrant women and Canadian-born women of low socio-economic status regarding
      barriers and enablers associated with cervical cancer screening, in order to
      inform core elements of a strategy that would be acceptable across multiple
      underscreened groups. METHOD: Within a health behaviour framework, we used a
      qualitative explanatory multiple-case study approach consisting of focus group
      interviews (n = 11) in Hamilton, Canada. Participants were newly immigrated (1-5
      years) women and a group of Canadian-born women of low socio-economic status; all
      participants were in the age range 35-69 years and married. Language groups were
      Arabic, Cantonese, Somali, Dari (Afghanistan) and Spanish (Latin America). Two
      separate focus groups for each ethnolinguistic group were conducted; one in
      English and one in the native language. A template approach to analysis was used.
      RESULTS: All groups indicated a strong need for information on necessity of
      screening and on how the procedure is done. Use of a video and a group discussion
      format were desired strategies. Women had positive feelings about being proactive
      for their health even if prevention had not been the norm in their home
      countries. There were differences between groups with respect to preferring a
      female clinician, which was a higher priority than language congruence with the
      provider. Only Chinese and Arabic groups discussed embarrassment and modesty as
      barriers. CONCLUSION: Addressing key knowledge gaps around cervical cancer
      screening through personal approaches, educational videos and invitations may be
      useful core strategies to remove stigma and fear around screening and improve
      uptake across multiple ethnic groups and in women of lower socioeconomic status.

PMID- 21714326
TI  - Re: Schechter MT, Kendall P. Counterpoint: is there a need for heroin
      substitution treatment in Vancouver's Downtown Eastside? Yes there is, and in
      many other places. CJPH 2011;102(2):87-89.

PMID- 21714327
TI  - Re: Outram SM. Epidemiology and bioethics: a plea for reconnecting with the
      public. [Ethics in public health] Can J Public Health 2011;102(1):4-6.

PMID- 21714329
TI  - The "regional" Medical School in Fiji: 125 years young--what an amazing journey.

PMID- 21714328
TI  - Fiji School of Medicine 1885-2010 celebrating 125 years.

PMID- 21714330
TI  - The Fiji School of Medicine. A history, 1886-1971. 1971.

PMID- 21714331
TI  - The evolution of primary heath care in Fiji: past, present and future.
AB  - Health policy initiatives are under-analysed in the Pacific region. Understanding
      how health policies develop and evolve is a first step towards improving their
      quality and contextual appropriateness. Through a document review and key
      informant interviews, this paper examines the evolution of primary health care in
      Fiji from 1975 to 2009 focusing on priority-setting, funding, implementation,
      political economy, the cultural context and interactions among communities,
      government and donors. Lessons learned from more than 30 years of experience with
      community health in Fiji are highlighted and reveal high levels of contestation
      over health policy processes. The paper identifies factors for consideration in
      renewed primary health interventions and calls for greater government ownership
      of priority-setting processes, more clarity on the links between policy and
      funding, more focus on evidence-based policy, greater awareness by development
      partners of the risks of policy imposition, and a deeper analysis of political
      economy and culture in relation to health sector policies.

PMID- 21714332
TI  - Building an economic case for food interventions in the Pacific.
AB  - Diet-related health problems are a major issue throughout the Pacific region.
      Micronutrient deficiencies are widespread and rates of non-communicable diseases
      are increasing. There is a need for food-related policy interventions to improve
      the quality of the food supply and to enhance access to a healthy diet. To
      support the promotion and eventual implementation of these interventions, it is
      vital that the costs and impacts of the interventions are known. This paper
      outlines a project being undertaken in the region to develop cost-effectiveness
      models for food interventions in order to help build the case for action.

PMID- 21714333
TI  - Improving integration and coordination of funding, technical assistance, and
      reporting/data collection: recommendations from CDC and USAPI stakeholders.
AB  - BACKGROUND: Current US Federal funding mechanisms may foster program silos that
      disable sharing of resources and information across programs within a larger
      system of public health services. Such silos present challenges to USAPI
      communities where human resources, health infrastructure, and health financing
      are limited. Integrative and coordinated approaches have been recommended. The
      CDC Pacific Islands Integration and Coordination project was initiated by the
      Division of Cancer Prevention and Control (DCPC). Its project aim was to identify
      ways for the CDC to collaborate with the USAPI in improving CDC activities and
      processes related to chronic disease. This article focuses on recommendations for
      improving coordination and integration in three core areas of health services
      programming: funding, program reporting/data collection and analysis, and
      technical assistance. METHOD: Preliminary information on challenges and issues
      relevant to the core areas was gathered through site visits, focus groups, key
      informant interviews, and other sources. This information was used by stakeholder
      groups from the CDC and the USAPI to develop recommendations in the core
      programming areas. Recommendations generated at the CDC and USAPI stakeholder
      meetings were prepared into a single set of recommendations and stakeholders
      reviewed the document for accuracy prior to its dissemination to CDC's National
      Center for Chronic Disease Prevention and Health Promotion programs management
      and staff. RESULTS: Key recommendations, include: (1) consideration of resource s
      and other challenges unique to the USAPI when reviewing funding applications, (2)
      consideration of ways to increase flexibility in USAPI use of program funds, (3)
      dedicate funding and human resources for technical assistance, (4) provide
      opportunities for capacity-building across programs and jurisdictions, (5)
      consider ways to more directly link program reporting with technical assistance.
      CONCLUSIONS: This project provided a unique opportunity for CDC and USAPI
      stakeholders to share diverse perspectives on challenges to public health
      programs in the USAPI. Despite diverse experiences, the final set of
      recommendations reflected a high level of concordance between USAPI and CDC
      stakeholders on ways to improve coordination and integration of CDC processes and
      activities in the three core areas. Recommendations have informed some actions
      already initiated by the DCPC, including the dedication of funds for leadership
      institutes aimed at enhancing USAPI capacity for sustainable, integrated regional
      and jurisdictional cancer control infrastructure. Such efforts are an important
      beginning, but more remains to be done. Indicated is the need for continuous
      dialogue and collaboration. While this project focused on the USAPI, our results
      may be relevant to those interested in inter-organizational collaborations,
      medically underserved areas, public health services programs, and community-based
      participatory approaches.

PMID- 21714334
TI  - Comparisons of health expenditure in 3 Pacific Island Countries using National
      Health Accounts.
AB  - National Health Accounts (NHA) is an important monitoring tool for health policy
      and health systems strengthening. A pilot project amongst three Pacific Island
      Countries (PICs) to assist in developing their NHAs, allowed these countries to
      identify their sources of health funds, the health providers on which these funds
      are spent, and the types of health goods and services provided. In this paper we
      report some of the findings from the NHA exercises in FSM, Fiji and Vanuatu. The
      development of these NHA country reports have allowed these countries to better
      understand the flow of financial resources from financing agents, to health
      providers, and to health functions. The NHA findings across the three countries
      enabled a comparative analysis of health expenditures between the three countries
      as well as with countries in the Asia Pacific Region.

PMID- 21714335
TI  - Graduation ceremony 1975.

PMID- 21714336
TI  - HIV and AIDS responses of health care training institutions in the Pacific
      Islands--a literature review.
AB  - The purpose of this review paper is to provide information on the current roles
      of Pacific health care training institutions response to the HIV pandemic and to
      identify ways to scale up their response. The evidence presented here comes
      primarily from few published papers, unpublished literature and anecdotal
      evidence through interviews with health care training institute staff in the
      region. Studies from high prevalence countries in the Sub - Sahara African and
      Caribbean Countries reveal that higher tertiary institutions played an important
      role in the fight against HIV, through the development of HIV related policies,
      research, partnership networks, community awareness, treatment and care services
      and curriculum in response to the pandemic. While these responses were initiated
      at a time when incidence had seemed to reach an uncontrollable level the
      processes generated many important lessons. Very little is known about the
      response of health care training institutions in the Pacific. Detailed studies
      need to be implemented to assess and verify the level of responses in the health
      care training institutions. What is needed now is political will and resources to
      support and scale up HIV responses at Pacific health care training institutions.

PMID- 21714337
TI  - Fiji School of Medicine graduation ceremony 5/12/80.

PMID- 21714338
TI  - Vitello-intestinal duct fistula--a rare presentation of a patent vitello
      intestinal duct: a case report.
AB  - Patent Vitello-intestinal Duct (VID) results as of failed obliteration of the
      fetal omphalocele coelom (herniated loops of intestine in the umbilical cord)
      during the development of the midgut. We report a case of an infant who presented
      at 11 months of the age with history of persistent umbilical discharge since
      birth. The VID was confirmed with a fistulogram using gastrograffin contrast
      studies and a wedge resection with primary anastomosis. The infant was discharged
      5 days post-op without any post-operative complications. This case report
      highlight a rare cause of umbilical discharge and the surgical intervention
      required.

PMID- 21714339
TI  - Missed diagnosis: blunt abdominal injury-case report.
AB  - Acute pancreatitis is an uncommon finding in children and therefore one must have
      a high index of suspicion when evaluating children with blunt abdominal trauma.
      It can cause severe morbidity and mortality and requires one to be vigilant to
      make the diagnosis and to ensure appropriate management. We report on a case of
      acute pancreatitis that had diagnostic and management dilemmas at Colonial War
      Memorial Hospital (CWMH) in Fiji.

PMID- 21714340
TI  - An ingested toothbrush.
AB  - Toothbrush ingestion is rare and most cases are seen in anorexic or bilumic young
      women or associated with mental retardation or schizophrenia. We report a case of
      accidental swallowing of a toothbrush in a man with no such background
      psychiatric disorder. The toothbrush was impacted in the duodenum and could not
      be removed endoscopically. It was removed via a laparotomy and the patient made
      an uneventful recovery. The pathophysiology, presentation and various techniques
      reported for endoscopic removal have been reviewed. If endoscopic removal is not
      possible the toothbrush must be removed by operation, as spontaneous passage is
      unknown.

PMID- 21714341
TI  - Recurrent abdominal pain post appendectomy--a rare case.
AB  - Right iliac fossa pain in young adults who have previously had an appendicectomy
      represents a diagnostic challenge. In such cases it is important to review the
      histology of the appendix and the previous operation notes. The appendix stump,
      if left long following an appendectomy, can result in chronic appendicitis of the
      stump, or it can rarely develop into a mucocele. This case report describes a
      patient with an appendix stump mucocele who presented with chronic pain under the
      right iliac fossa incision and was successfully treated by laparoscopic
      resection.

PMID- 21714342
TI  - Adult postoperative intussusception following transverse colectomy--a rare
      complication.
AB  - Postoperative intussusception is a rare cause of intestinal obstruction in
      adults. We report a case of postoperative jejunojejunal intussusception in a 45
      year-old female following a transverse colectomy for a colonic tumour. The
      patient presented with intermittent bowel obstruction on the fourth day of her
      operation. A re-laparotomy performed on day twenty one revealed a jejunojejunal
      intussusception as the cause for the obstruction. This is a rare cause of
      postoperative small bowel obstruction, and the pathogenesis and diagnosis of
      postoperative intussusception in the adult is discussed in the case report.

PMID- 21714343
TI  - Guillain-Barre syndrome associated with typhoid fever. A case study in the Fiji
      Islands.
AB  - Guillian-Barre Syndome is a very rare neurological complication of typhoid. We
      report a young girl with blood culture proven typhoid septicaemia that developed
      this very rare neurological complication of the disease. Following treatment with
      intravenous antibiotics she improved but developed the complications during the
      third week of her illness while admitted in hospital. To our knowledge this
      neurological complication of typhoid has never been reported in Fiji.

PMID- 21714344
TI  - A case report: simple and effective external fixator for finger fractures.
AB  - A case report on a very simple and very effective technique of achieving finger
      fracture fixation. This cost effective and yet simple tool and technique of
      immobilization is cheap and can be readily used in the South Pacific. This
      procedure provides us with an alternative to amputation of the digit. It is also
      a very reliable and cost effective procedure which could be easily taught to
      junior surgical registrars.

PMID- 21714345
TI  - Progress in medical education at the Fiji School of Medicine.

PMID- 21714346
TI  - Ciguatera fish poisoning and environmental change: a case for strengthening
      health surveillance in the Pacific?
AB  - Ciguatera Fish Poisoning (CFP), a significant public health problem in the
      Pacific, is intrinsically linked to the health of coral reef ecosystems.
      Incidence data on CFP could therefore be used, in theory, as indicators of
      disruption to coral reefs. Some disruptions, such as increasing sea surface
      temperatures, result from global environmental change--therefore suggesting that
      CFP is likely to become an increasing public health problem in the region. The
      proactive management of increasing numbers of cases will depend on an
      understanding of the ecology of the disease, sound health surveillance systems to
      report cases of CFP including appropriate case definitions, and quantifiable
      correlations between case numbers and environmental variables. Here, we briefly
      review the knowledge about these components in Pacific Island Countries and
      Territories (PICTs), including summarising regional variation in symptoms of CFP
      cases, investigating media as an enhanced surveillance tool, and summarising
      regional environmental drivers of CFP cases. We conclude that CFP could be an
      important indicator of the health of reef ecosystems in the face of global
      climate change and more novel approaches such as combining environmental and
      health data, need to be implemented to improve surveillance of CFP.

PMID- 21714347
TI  - Generic medicines--how confident should we be?

PMID- 21714349
TI  - Writing an academic discussion.

PMID- 21714348
TI  - Western epistemology: a stranger in a strange land?
AB  - Westernization in the Pacific, as in the world, brought with it many old truths
      and new ideas. It brought new belief systems that were widely accepted and
      technologies that mostly proved useful. But it also brought something that it
      never fully put into words, although the brightest of students attending the best
      of schools may have had a glimpse of it. It's not a secret but, somehow, it's
      rarely discussed. When Westerners came they claimed to know an awful lot of
      things. But how did they know what they claimed to know? What was their way of
      knowing things? This paper discusses the various ways of knowing, with special
      reference to scientific knowledge and its epistemological basis, and to the
      nature of the body of knowledge it generates and protects. The objective is to
      provide a short history of western thought and a foundation for young scientist
      who need more than the successes of technology to understand how they know the
      things they claim to know.

PMID- 21714350
TI  - The Fiji School of Medicine: changes in 1984.

PMID- 21714351
TI  - An address delivered by Hon. Dr A.N. Kurisaqila, Minister for Health & Social
      Welfare, at the Fiji School of Medicine graduation? ceremony, on 5th December,
      1984.

PMID- 21714352
TI  - Introduction to the World Bank flagship course on health systems strengthening
      and health financing.

PMID- 21714353
TI  - Fiji School of Medicine produced practical surgeons by Dr. J. S. Baravilala (24th
      August, 2000).

PMID- 21714354
TI  - Reflections of FSM student life and career developments.

PMID- 21714355
TI  - New perspectives in the psychotherapy of psychoses at onset: evidence,
      effectiveness, flexibility, and fidelity.

PMID- 21714356
TI  - Family interventions in early psychosis: specificity and effectiveness.
AB  - The first episode of psychosis frequently occurs during adolescence and early
      adulthood, and is associated with high levels of trauma, affective disturbance
      and suicide. The social networks of service users often decrease significantly
      following the first onset, although many will remain in close contact with some
      family members particularly during the early phases. However, the negative impact
      of psychosis on families and their relationship with the identified service user
      are well documented. Family intervention is a recommended and evidence-based
      treatment in later psychosis. In this paper, we review the literature on family
      interventions in early psychosis in the context of new evidence for its efficacy
      and its routine incorporation in early intervention services for psychosis.

PMID- 21714357
TI  - Adherence and competence assessment in studies of CBT for psychosis: current
      status and future directions.
AB  - All good quality trials of psychological interventions need to check formally
      that therapists have used the techniques prescribed in the published therapy
      manuals, and that the therapy has been carried out competently. This paper
      reviews methods of assessing adherence and competence used in recent large-scale
      trials of Cognitive Behaviour Therapy (CBT) for psychosis in the UK carried out
      by our research groups. A combination of the Cognitive Therapy Rating Scale and
      specific versions of the Cognitive Therapy for Psychosis Adherence Scales
      provides an optimal assessment of adherence and competence. Careful assessment of
      the competence and adherence can help identify the procedures actually carried
      out with individuals within trials. The basic use of such assessments is to
      provide an external check on treatment fidelity on a sample of sessions. Such
      assessment can also provide the first step towards moving research towards making
      sense of CBT for psychosis as a complex intervention and identifying which
      techniques work for which problems of people with psychosis, at which stages of
      disorder?

PMID- 21714358
TI  - The efficacy of psychotherapy in reducing post-psychotic trauma.
AB  - There is now growing evidence to suggest that the experience of psychosis may be
      so traumatic for some that it can lead to Post Traumatic Stress Disorder (PTSD)
      type symptoms or post-psychotic trauma symptoms (PPTS). There is, however, less
      knowledge about what psychological interventions may be helpful in reducing these
      symptoms. Evidence from the literature, to date, suggests that of the seven
      studies that have addressed this issue only four were randomized controlled
      trials (RCTs). However, all these studies included less than 100 patients with
      the vast majority reporting positive results. Overall, it seems that although
      cognitive-behavioural treatment (CBT)-based psychological interventions appear to
      be efficacious in the treatment of PPTS, the studies are too small to draw any
      firm conclusions and should be subjected to larger good-quality RCTs. Further
      research will also need to establish the role of mediating variables such as
      shame and depression in the treatment of PPTS.

PMID- 21714359
TI  - Why it is important to include unpublished data in systematic reviews.
AB  - It is known that studies with statistically significant results have a higher
      probability to be published (publication bias). Therefore, studies with no
      statistically significant differences (or not favoring the investigational drug)
      may not be found in commonly accessed databases and remain unpublished. Moreover,
      unpublished data may also refer to information that are not included in study
      reports published in scientific journals but that may be important to estimate
      study outcomes. Retrieving unpublished evidence represents a compelling challenge
      for researchers, and in the present paper we explore how to do it.

PMID- 21714360
TI  - Diffusion imaging studies of white matter integrity in bipolar disorder.
AB  - Diffusion tensor imaging (DTI) is a neuroimaging technique with a potential to
      elucidate white matter integrity. Recently, it has been used in the field of
      psychiatry to further understand the pathophysiology of major diseases, including
      bipolar disorder (BD). This review sought to focus on existing DTI findings on
      white matter organization in BD.

PMID- 21714361
TI  - Treating co-morbid chronic medical conditions and anxiety/depression.
AB  - AIMS: This systematic review examines interventions for care of people with co
      morbid chronic medical illness and anxiety/depression disorders--a group with
      high risks for morbidity and mortality. METHODS: Systematic search of Medline
      1995 to January 2011 for randomized controlled trials of treatment interventions
      designed for adult outpatients with diagnosed chronic medical illness (diabetes
      mellitus, cardiovascular disorders, and chronic respiratory disorders) and
      anxiety/depression disorders. RESULTS: Six trials studied complex interventions
      based on the chronic care model, and eight trials studied psychosocial
      interventions. Most interventions addressed the mental health aspect of the co
      morbidity and showed improvements in anxiety/depression but not in the co-morbid
      medical disorder. CONCLUSIONS: Further research might focus on interventions
      integrating mental health treatment with enhanced medical care components,
      incorporating shared-decision making and information technology advances.

PMID- 21714362
TI  - A comparison of the implementation of assertive community treatment in Melbourne,
      Australia and London, England.
AB  - AIMS: The efficacy of Assertive Community Treatment (ACT) is well established in
      the USA, and to a lesser extent in Australia, whereas UK studies suggest little
      advantage for ACT over usual care. Implementation of ACT varies and these
      differences may explain variability in reported efficacy. We aimed to investigate
      differences in ACT implementation between Melbourne, Australia and London, UK.
      METHODS: In a cross-sectional survey, we investigated team organisation, staff
      and client characteristics from four Melbourne ACT teams using almost identical
      methods to the Pan London Assertive Outreach studies of 24 ACT teams. RESULTS:
      Client characteristics, staff satisfaction and burnout were very similar. Three
      of four Melbourne teams made over 70% of client contacts 'in vivo' compared to
      only one-third of comparable London teams, although all teams were rated as 'ACT
      like'. Melbourne teams scored more highly on team approach. Three quarters of
      clients were admitted in the preceding 2 years but Melbourne clients had shorter
      stays. CONCLUSIONS: Differences in the implementation of 'active components' of
      home treatment models that have been associated with better client outcomes (home
      visiting, team approach) may explain international differences in ACT efficacy.
      Existing fidelity measures may not adequately weight these important elements of
      the model.

PMID- 21714363
TI  - What to do about depression? Help-seeking and treatment recommendations of the
      public.
AB  - AIMS: Several population studies on beliefs about depression carried out in
      western countries during the 1990s have shown that the public clearly favors
      psychotherapy over antidepressant medication. The present study examines whether
      this phenomenon still exists at the end of the first decade of the twenty-first
      century. MATERIALS AND METHODS: In 2009, a telephone survey was conducted among
      the population of Vienna aged 16 years and older (n = 1205). A fully structured
      interview was administered which began with the presentation of a vignette
      depicting a case of depression fulfilling the diagnostic criteria of DSM-IV for a
      moderate depressive episode. RESULTS: Psychotherapists were most frequently
      endorsed as source of professional help. Antidepressant medication still was more
      frequently advised against than recommended. Respondents familiar with the
      treatment of depression tended to be more ready to recommend to seek help from
      mental health professionals and to endorse various treatment options,
      particularly medication. CONCLUSION: At the end of the first decade of this
      century, there still exists a large gap between the public's beliefs and what
      mental health professionals consider appropriate for the treatment of depression.
      Therefore, further effort to improve the public's mental health literacy seems
      necessary.

PMID- 21714364
TI  - Antipsychotic utilisation and polypharmacy in Italian residential facilities: a
      survey.
AB  - OBJECTIVE: To evaluate the prescribing practices in psychiatric residential
      facilities, with particular focus both on the antipsychotic dose and polypharmacy
      as well as the variation of antipsychotic patterns during a patient's stay within
      the facilities. METHODS: Fifteen residential facilities of Liguria region in
      Italy were included. Data were collected through a chart review during a one-day
      census. Frequency of psychotropic patterns was estimated. Different non
      parametric tests were used to analyse the changes in prescription patterns as
      well as the relationship among antipsychotic dose, the number of antipsychotics
      and anticholinergic use. RESULTS: The study sample includes 362 patients, 61.9%
      males. On the census day 77.5% of patients received psychotropic polypharmacy and
      57.2% antipsychotic polypharmacy. Antipsychotic polypharmacy was related to the
      total antipsychotic daily dose and to anticholinergic use. A trend towards an
      increase of antipsychotic and psychotropic polypharmacy and higher doses of
      antipsychotics over the period of stay within the facilities was noted. This
      tendency was related to the length of stay in the facility. CONCLUSIONS: Compared
      to earlier studies in the same clinical environment a significant increase in the
      use of psychotropic and antipsychotic polypharmacy was observed. The risk of
      prescribed polypharmacy seems to be related to time spent in the facility.

PMID- 21714365
TI  - Needs-oriented discharge planning for high utilisers of psychiatric services:
      multicentre randomised controlled trial.
AB  - AIMS: Attempts to reduce high utilisation of mental health inpatient care by
      targeting the critical time of hospital discharge are rare. In this study, we
      test the effect of a needs-oriented discharge planning intervention on number and
      duration of psychiatric inpatient treatment episodes (primary), as well as on
      outpatient service use, needs, psychopathology, depression and quality of life
      (secondary). METHODS: Four hundred and ninety-one adults with a defined high
      utilisation of mental health care gave informed consent to participate in a
      multicentre RCT carried out at five psychiatric hospitals in Germany (Dusseldorf,
      Greifswald, Regensburg, Ravensburg and Gunzburg). Subjects allocated to the
      intervention group were offered a manualised needs-led discharge planning and
      monitoring intervention with two intertwined sessions administered at hospital
      discharge and 3 months thereafter. Outcomes were assessed at four measurement
      points during a period of 18 months following discharge. RESULTS: Intention-to
      treat analyses showed no effect of the intervention on primary or secondary
      outcomes. CONCLUSIONS: Process evaluation pending, the intervention cannot be
      recommended for implementation in routine care. Other approaches, e.g. team-based
      community care, might be more beneficial for people with persistent and severe
      mental illness.

PMID- 21714366
TI  - Reported stigma and discrimination by people with a diagnosis of schizophrenia.
AB  - AIMS: This article examines the extent of stigma and discrimination as reported
      by people with a diagnosis of schizophrenia. The hypothesis is that when people
      express in their own words the discrimination they experience such discrimination
      will be found to be widespread. METHODS: Seventy-five people with a diagnosis of
      schizophrenia from 15 different countries were interviewed with a mixed methods
      instrument to assess reported discrimination. The data were analysed for
      frequency counts and then a thematic analysis was performed. A conceptual map is
      provided. RESULTS: The study was a cross-cultural one but, contrary to
      expectations, few transnational differences were found. The main hypothesis was
      supported. Conversely, we found that when participants reported 'positive
      discrimination', this could as easily be conceptualised as being treated
      similarly to how others in society would expect to be treated. CONCLUSION:
      Negative discrimination is ubiquitous and sometimes connotatively very strong,
      with reports of humiliation and abuse. 'Positive discrimination' conversely
      indicates that people with a mental illness diagnosis expect discrimination and
      are grateful when it does not occur. The literature on self-stigma is discussed
      and found wanting. Similarly, the theory that contact with mentally ill people
      reduces stigma and discrimination is not fully supported by our results.

PMID- 21714367
TI  - Neuro-imaging of mindfulness meditations: implications for clinical practice.

PMID- 21714368
TI  - The US health system is both superlative and abysmal.

PMID- 21714369
TI  - Interview with Patrick A. Charmel, FACHE, president and chief executive officer
      of Griffin Hospital. Interview by Stephen J O'Connor.

PMID- 21714370
TI  - What every CEO should know about Medicare's recovery audit contractor program.

PMID- 21714371
TI  - Three "brutal facts" that provide strategic direction for healthcare delivery
      systems: preparing for the end of the healthcare bubble.

PMID- 21714372
TI  - Exploring the business case for ambulatory electronic health record system
      adoption.
AB  - Widespread implementation and use of electronic health record (EHR) systems has
      been recognized by healthcare leaders as a cornerstone strategy for
      systematically reducing medical errors and improving clinical quality. However,
      EHR adoption requires a significant capital investment for healthcare providers,
      and cost is often cited as a barrier. Despite the capital requirements, a true
      business case for EHR system adoption and implementation has not been made. This
      is of concern, as the lack of a business case can influence decision making about
      EHR investments. The purpose of this study was to examine the role of business
      case analysis in healthcare organizations' decisions to invest in ambulatory EHR
      systems, and to identify what factors organizations considered when justifying an
      ambulatory EHR. Using a qualitative case study approach, we explored how five
      organizations that are considered to have best practices in ambulatory EHR system
      implementation had evaluated the business case for EHR adoption. We found that
      although the rigor of formal business case analysis was highly variable,
      informants across these organizations consistently reported perceiving that a
      positive business case for EHR system adoption existed, especially when they
      considered both financial and non-financial benefits. While many consider EHR
      system adoption inevitable in healthcare, this viewpoint should not deter
      managers from conducting a business case analysis. Results of such an analysis
      can inform healthcare organizations' understanding about resource allocation
      needs, help clarify expectations about financial and clinical performance metrics
      to be monitored through EHR systems, and form the basis for ongoing
      organizational support to ensure successful system implementation.

PMID- 21714373
TI  - Physician and practice characteristics associated with longitudinal increases in
      electronic health records adoption.
AB  - This article identifies practice- and physician-related characteristics
      associated with the increased use of EHRs by physicians in outpatient practices.
      Two Florida surveys conducted in 2005 and 2008 on physician use of EHRs were
      examined to determine the practice and physician characteristics associated with
      increased EHR use over time. Based on multivariate analysis, several variables
      were found to influence increased EHR adoption. Practice variables included
      participation in a single-specialty practice and percentage of Medicare patients
      in the practice, but not percentage of Medicaid patients in the practice.
      Physician characteristics included younger physician age, but not specialty nor
      years practicing in the community. Factors associated with EHR adoption at any
      given point in time did not necessarily predict longitudinal increases in EHR
      adoption. These results are important for physicians to consider in their
      potential adoption of EHRs and should also be considered by policymakers
      interested in promoting increased use of EHRs by physicians.

PMID- 21714374
TI  - Developing a transfer center in a tertiary cancer center: streamlining access and
      communication to accommodate increasing demand for service.
AB  - Hospital-to-hospital transfers in a tertiary cancer center present an unusual set
      of problems involving a diverse group of acutely ill patients with highly
      specialized needs. The level and urgency of care required and the costs of
      providing optimal management often are exceedingly high. We present the
      administrative issues involved during a major revamping and streamlining of the
      Transfer Center at The University of Texas MD Anderson Cancer Center. The impetus
      for change included overuse of the emergency facility as a triage center for
      transferred patients, lack of adequate preadmission medical and financial
      screening of patients in anticipation of a transfer, a suboptimal level of
      physician-to-physician handoff communication, and insufficient protocols for
      prioritizing potential admissions and thus optimizing the institution's limited
      resources. During implementation of these revised policies, additional concerns
      were identified, including reluctance to modify established protocols and an
      inability to ensure the arrival of non-emergent transfer patients at our
      institution during daytime hours. Prioritizing admissions based on the degree of
      urgency and available resources required ongoing flexibility in accepting new
      concepts and ideas. The success of the project is documented in this report, as
      are suggestions for how other centers that experience similar challenging
      reorganizations can apply the lessons learned from our endeavors.

PMID- 21714375
TI  - Environmental exposures in the era of climate change.

PMID- 21714376
TI  - Health impacts of climate change and biosecurity in the Asian Pacific region.
AB  - Our climate is changing as a result of human activity, and such changes have the
      potential to have a significant impact on human health. The basic requirements
      for health--clean air, safe drinking water, sufficient food and secure shelter-
      are all vulnerable to climate change. Low-income developing countries are
      especially vulnerable; no country, however, is totally immune. In Australia, we
      are already seeing evidence of the health effects of climate change with an
      increase in temperature-related food poisoning events and an increase in mosquito
      borne infections, including Ross River virus and Dengue fever. In the Asian
      Pacific region the issues identified as most pressing vary from country to
      country, but a common theme is a lack of public understanding and education and
      lack of capacity for implementing mitigation strategies. Strategies addressing
      the health impacts of climate change must incorporate the principles of social
      justice and equity within the region.

PMID- 21714377
TI  - Exposures to lead.
AB  - The Pacific Basin Consortium for Environment and Health hosted a workshop on
      Exposures to Lead. Speakers from Australia and the United States of America
      addressed current research knowledge on lead exposures and health effects in
      children, risk assessment and communication issues in dealing with lead exposure
      sources, different methods for assessing exposure, and the variety of scenarios
      where lead still remains a pollutant of concern. Mining continues to be a source
      of lead for many communities, and approaches to reducing exposures in these
      settings present particular challenges. A Perth Declaration for the Global
      Reduction of Childhood Lead Exposure was signed by participants of the meeting
      and is aimed at increasing attention to the need to continue to assess lead in
      the environment and to develop strategies to reduce lead in the environment and
      exposure by communities.

PMID- 21714378
TI  - The status of water and sanitation among Pacific Rim nations.
AB  - Analysis of relationships among national wealth, access to improved water supply
      and sanitation facilities, and population health indices suggests that the
      adequacy of water resources at the national level is a poor predictor of economic
      development--namely, that low water stress is neither necessary nor sufficient
      for economic development at the present state of water stress among Pacific Rim
      nations. Although nations differ dramatically in terms of priority provided to
      improved water and sanitation, there is some level of wealth (per capita GNP) at
      which all nations promote the development of essential environmental services.
      Among the Pacific Rim countries for which there are data, no nation with a per
      capita GNP > US$18,000 per year has failed to provide near universal access to
      improved water supply and sanitation. Below US$18,000/person-year, however, there
      are decided differences in the provision of sanitary services (improved water
      supply and sanitation) among nations with similar economic success. There is a
      fairly strong relationship between child mortality/life expectancy and access to
      improved sanitation, as expected from the experiences of developed nations. Here
      no attempt is made to produce causal relationships among these data. Failure to
      meet Millennium Development Goals for the extension of improved sanitation is
      frequently evident in nations with large rural populations. Under those
      circumstances, capital intensive water and sanitation facilities are infeasible,
      and process selection for water/wastewater treatment requires an adaptation to
      local conditions, the use of appropriate materials, etc., constraints that are
      mostly absent in the developed world. Exceptions to these general ideas exist in
      water-stressed parts of developed countries, where water supplies are frequently
      augmented by water harvesting, water reclamation/reuse, and the desalination of
      brackish water resources. Each of these processes involves public acceptance of
      water resources that are at least initially of inferior quality. Despite
      predictions of looming increases in water stress throughout the world, adaptation
      and resourcefulness generally allow us to meet water demand while pursuing
      rational economic development, even in the most water-stressed areas of the
      Pacific Rim.

PMID- 21714379
TI  - Hazardous waste in the Asian Pacific region.
AB  - The production and disposal of hazardous waste remains a substantial problem in
      the Asian Pacific region. Remediation of waste disposal sites, including landfill
      sites, is attracting considerable research attention within the region. A
      recognition of the need for community engagement in this process is also growing.
      This article reviews the work presented in the Hazardous Waste sessions at the
      Pacific Basin Consortium for Environment and Health held in November 2009 in
      Perth.

PMID- 21714380
TI  - Emerging issues in the Pacific Basin.
AB  - This review provides a snapshot of some key environmental health issues that will
      provide ongoing challenges for the Pacific Basin region in the coming decades. It
      is clear that climate change as well as the rapidly increasing production of
      environmental pollutants are significant emerging environmental health issues. To
      date, research in these areas is limited, and the consequences of potential
      changes in disease vector distribution, disease outbreaks associated with climate
      change-induced severe weather events, and the consequences of chronic exposure to
      engineered nanoparticles and persistent organic pollutants (POPs), particularly
      in children, remain to be determined. Clearly, any progress in (i) predicting the
      outcomes of potential environmental health issues in the future, (ii) identifying
      subpopulations (at local, national, and international levels) that are at risk,
      and (iii) establishing measures to limit the impact of these issues in terms of
      public health, will require a coordinated effort from scientists,
      epidemiologists, monitoring agencies, governments, and aid agencies.

PMID- 21714381
TI  - Baseline determination in social, health, and genetic areas in communities
      affected by glyphosate aerial spraying on the northeastern Ecuadorian border.
AB  - The northeastern Ecuadorian border has undergone aerial spraying with an
      herbicide mix that contains surfactants and adjuvants, executed by the Colombian
      Government. The purpose of this study was to diagnose social, health, and genetic
      aspects of the people affected by glyphosate. For this objective to be achieved,
      144 people were interviewed, and 521 medical diagnoses and 182 peripheral blood
      samples were obtained. Genotyping of GSTP1 Ile105Val, GPX-1 Pro198Leu, and XRCC1
      Arg399Gln polymorphisms were analyzed, using PCR-RFLP technique. The assessment
      of chromosomal aberrations was performed, obtaining 182 karyotypes. Malnutrition
      in children was 3%. Of the total population, 7.7% had children with
      malformations, and the percentage of abortions was 12.7%. Concerning genotyping,
      individuals with GSTP1 Val/Val obtained an odds ratio of 4.88 (p < 0.001), and
      Ile/Val individuals, together with Val/Val individuals, had an odds ratio of 2.6
      (p < 0.05). In addition, GPX-1 Leu/Leu individuals presented an odds ratio (OR)
      of 8.5 (p < 0.05). Regarding karyotyping, the 182 individuals had normal
      karyotypes. In conclusion, the study population did not present significant
      chromosomal and DNA alterations. The most important social impact was fear. We
      recommend future prospective studies to assess the communities.

PMID- 21714382
TI  - Air pollution: a tale of two countries.
AB  - The fast growing economies and continued urbanization in Asian countries have
      increased the demand for mobility and energy in the region, resulting in high
      levels of air pollution in cities from mobile and stationary sources. In
      contrast, low level of urbanization in Australia produces low level of urban air
      pollution. The World Health Organization estimates that about 500,000 premature
      deaths per year are caused by air pollution, leaving the urban poor particularly
      vulnerable since they live in air pollution hotspots, have low respiratory
      resistance due to bad nutrition, and lack access to quality health care.
      Identifying the differences and similarities of air pollution levels and its
      impacts, between Indonesia and Australia, will provide best lesson learned to
      tackle air pollution problems for Pacific Basin Rim countries.

PMID- 21714383
TI  - Health effects of persistent organic pollutants: the challenge for the Pacific
      Basin and for the world.
AB  - Persistent organic pollutants include some organo-metals, such as methylmercury;
      lipophilic halogenated organics, such as dioxins, polychlorinated biphenyls,
      chlorinated pesticides, and polybrominated flame retardants; and perfluorinated
      compounds used as repellants. These compounds are resistant to degradation both
      in the environment and in the human body and tend to bioaccumulate within the
      food chain. Persistent organic pollutants cause a variety of adverse health
      effects, including cancer, immune system suppression, decrements in cognitive and
      neurobehavioral function, disruption of sex steroid and thyroid function, and at
      least some of them increase the risk of chronic diseases, such as hypertension,
      cardiovascular disease, and diabetes. Some compounds are byproducts of industry
      and combustion. Although the manufacture and use of most man-made chemicals has
      been reduced in recent years, the levels currently present in the population are
      still associated with an elevated risk of human disease. Others are still
      manufactured and used. These are dangerous chemicals that have contaminated even
      areas remote from the industrialized world, such as the polar regions.

PMID- 21714384
TI  - Arsenic geochemistry and human health in South East Asia.
AB  - Arsenic occurs naturally in many environmental components and enters the human
      body through several exposure pathways. Natural enrichment of arsenic may result
      in considerable contamination of soil, water, and air. Arsenic in groundwater can
      exceed values hundreds of time higher than the concentration recommended for
      drinking water. Such exposure levels indicate a serious potential health risk to
      individuals consuming raw groundwater. Human activities that have an impact on
      the environment may increase the distribution of inorganic arsenic. Abandoned
      mines are of great concern due to the extremely high arsenic concentrations
      detected in mine drainage and tailings. Diet, drinking water, air, soil, and
      occupational exposures are all sources of inorganic arsenic for humans.
      Interdisciplinary efforts to better characterize the transport of arsenic and
      reactants that facilitate their release to the environment are important for
      human health studies. Multi-disciplinary efforts are needed to study diet,
      infectious disease, genetics, and cultural practices unique to each region to
      better understand human health risk and to design public health interventions.

PMID- 21714385
TI  - What makes a team smarter? More women.

PMID- 21714386
TI  - Before you make that big decision...
AB  - When an executive makes a big bet, he or she typically relies on the judgment of
      a team that has put together a proposal for a strategic course of action. After
      all, the team will have delved into the pros and cons much more deeply than the
      executive has time to do. The problem is, biases invariably creep into any team's
      reasoning-and often dangerously distort its thinking. A team that has fallen in
      love with its recommendation, for instance, may subconsciously dismiss evidence
      that contradicts its theories, give far too much weight to one piece of data, or
      make faulty comparisons to another business case. That's why, with important
      decisions, executives need to conduct a careful review not only of the content of
      recommendations but of the recommendation process. To that end, the authors
      Kahneman, who won a Nobel Prize in economics for his work on cognitive biases;
      Lovallo of the University of Sydney; and Sibony of McKinsey-have put together a
      12-question checklist intended to unearth and neutralize defects in teams'
      thinking. These questions help leaders examine whether a team has explored
      alternatives appropriately, gathered all the right information, and used well
      grounded numbers to support its case. They also highlight considerations such as
      whether the team might be unduly influenced by self-interest, overconfidence, or
      attachment to past decisions. By using this practical tool, executives will build
      decision processes over time that reduce the effects of biases and upgrade the
      quality of decisions their organizations make. The payoffs can be significant: A
      recent McKinsey study of more than 1,000 business investments, for instance,
      showed that when companies worked to reduce the effects of bias, they raised
      their returns on investment by seven percentage points. Executives need to
      realize that the judgment of even highly experienced, superbly competent managers
      can be fallible. A disciplined decision-making process, not individual genius, is
      the key to good strategy.

PMID- 21714387
TI  - The ambidextrous CEO.
AB  - Although most managers publicly acknowledge the need to explore new businesses
      and markets, the claims of established businesses on company resources almost
      always come first, especially when times are hard. When top teams allow the
      tension between core and speculative units to play out at lower levels of
      management, innovation loses out. At best, leaders of core business units dismiss
      innovation initiatives as irrelevancies. At worst, they see the new businesses as
      threats to the firm's core identity and values. Many CEOs take a backseat in
      debates over resources, ceding much of their power to middle managers, and the
      company ends up as a collection of feudal baronies. This is a recipe for long
      term failure, say the authors. Their research of 12 top management teams at major
      companies suggests that firms thrive only when senior teams lead ambidextrously-
      when they foster a state of constant creative conflict between the old and the
      new. Successful CEOs first develop a broad, forward-looking strategic aspiration
      that sets ambitious targets both for innovation and core business growth. They
      then hold the tension between innovation unit demands and core business demands
      at the very top of the organization. And finally they embrace inconsistency,
      allowing themselves the latitude to pursue multiple and often conflicting
      agendas.

PMID- 21714388
TI  - The innovation catalysts.
AB  - A few years ago the software development company Intuit realized that it needed a
      new approach to galvanizing customers. The company's Net Promoter Score was
      faltering, and customer recommendations of new products were especially
      disappointing. Intuit decided to hold a two-day, off-site meeting for the
      company's top 300 managers with a focus on the role of design in innovation. One
      of the days was dedicated to a program called Design for Delight. The centerpiece
      of the day was a PowerPoint presentation by Intuit founder Scott Cook, who
      realized midway through that he was no Steve Jobs: The managers listened
      dutifully, but there was little energy in the room. By contrast, a subsequent
      exercise in which the participants worked through a design challenge by creating
      prototypes, getting feedback, iterating, and refining, had them mesmerized. The
      eventual result was the creation of a team of nine design-thinking coaches-
      "innovation catalysts"--from across Intuit who were made available to help any
      work group create prototypes, run experiments, and learn from customers. The
      process includes a "painstorm" (to determine the customer's greatest pain point),
      a "soljam" (to generate and then winnow possible solutions), and a "code-jam" (to
      write code "good enough" to take to customers within two weeks). Design for
      Delight has enabled employees throughout Intuit to move from satisfying customers
      to delighting them.

PMID- 21714389
TI  - The paradox of excellence.
AB  - Why is it that so many smart, ambitious professionals are less productive and
      satisfied than they could be? Thomas DeLong, an academic and consultant to
      executives, and Sara DeLong, a psychiatrist, argue that it's often because
      they're afraid to demonstrate any sign of weakness. They're reluctant to ask
      important questions or try new approaches that push them outside their comfort
      zones. For high achievers, looking stupid or incompetent is anathema. So they
      stick to the tasks they're good at, even while the rest of the organization may
      be passing them by. In short, they'd rather do the wrong thing well than do the
      right thing poorly. They get stuck in this unproductive and unfulfilling pattern
      and can't break free. Of course, leaders in organizations bear some of the blame
      for this type of play-it-safe mind-set. They don't always want to hear that a
      person is struggling, nor do they necessarily reward risk taking, even though
      they might pay lip service to innovative initiative. The authors outline several
      steps that individuals can take to shake off fear and paralysis, including
      looking at past negative experiences from somebody else's point of view and
      seeking out safe ways to allow themselves to become vulnerable.

PMID- 21714390
TI  - How games could save the world.

PMID- 21714392
TI  - Exec revamp at Christus.

PMID- 21714391
TI  - MedCath plans to dissolve.

PMID- 21714393
TI  - Too much, too little. Country splurges on unneeded care while others lack access.

PMID- 21714394
TI  - Not the be-all, end-all ACOs are a start, but insurers, hospitals, patients all
      must do their part too.

PMID- 21714395
TI  - 'Journey to zero'. Clarity and focus lead hospital to efficiency.

PMID- 21714396
TI  - Collective anxiety. More state bills target benefits, bargaining rights.

PMID- 21714397
TI  - Not enough. ACO waivers need to be wide-ranging: providers.

PMID- 21714398
TI  - Feeling the heat. Healthcare at the center of long-simmering battles; are they
      set to boil over?

PMID- 21714399
TI  - Trust the clinicians. Processes that caused adverse events a more urgent problem
      than human error.

PMID- 21714400
TI  - Caring for kids, with technology by their side. Children's Medical's Durovich
      sees IT as tool to 'help us do what we do better'.

PMID- 21714401
TI  - How to stop superbugs.

PMID- 21714402
TI  - Optimizing impressioning?

PMID- 21714403
TI  - Bonded amalgams and their use in clinical practice.
AB  - There has been a move in recent years for operative dentists to use the benefits
      of adhesive technology when placing dental amalgam restorations. This paper
      describes the potential advantages of the bonded amalgam technique. These
      benefits include decreased microleakage between the cavity wall and the
      restorative material. This, in turn, may decrease post-operative sensitivity,
      pulpal inflammation and the incidence of recurrent caries. Extra retention for
      the restoration may also be provided and the need for cavities to rely on
      traditional retention and resistance form may be decreased or even eliminated,
      thus conserving precious tooth tissue. If the restoration is bonded then flexure
      during function in teeth may be decreased and, in the case of teeth exhibiting a
      cracked cusp, this may alleviate or eliminate symptoms. Bonding may also provide
      support to weakened tooth tissue which otherwise would have to be removed, so
      rendering cavities more conservative, and may increase the fracture resistance of
      the tooth. Clinical examples are included to illustrate some of these benefits.
      CLINICAL RELEVANCE: The use of adhesives to bond amalgam to tooth tissue offers
      potential advantages, although some of the current evidence is equivocal about
      their routine use.

PMID- 21714404
TI  - Domiciliary oral healthcare.
AB  - There is increasing demand for Domiciliary Oral Healthcare (DOHC) and the skills
      and equipment required to provide a quality, patient-centred service with careful
      assessment and management in a sometimes compromised situation. Commissioning of
      DOHC needs to be set in the context and current agenda of equality, diversity and
      human rights in both health and social care. Effective marketing and community
      engagement are required to promote awareness of how to access services amongst
      people confined to home and their families and carers. Training for the whole
      dental team should be available in order to address the concerns and problems
      encountered regarding the provision of DOHC. CLINICAL RELEVANCE: Members of the
      dental team should be aware of the skills required for DOHC and be familiar with
      using effective care pathways in relation to the provision of DOHC.

PMID- 21714405
TI  - Routine and emergency management guidelines for the dental patient with renal
      disease and kidney transplant. Part 2.
AB  - Aimed at the practitioner in Special Care Dentistry, this is the second article
      in a two-part series providing guidelines on the dental management of renal
      patients. Dentists working in Special Care Dentistry will frequently be called
      upon to manage dialysis patients, whether pre- or post-transplant. The following
      paper deals with guidance as to the assessment, work-up and management of such
      patients when undergoing specialist dental treatment. The key to safe treatment
      is careful assessment, discussion and planning with the relevant team members.
      CLINICAL RELEVANCE: This paper provides guidance to the special care dentist for
      the dental management of patients with renal disease, and highlights issues in
      patients who are either on dialysis or have a kidney transplant.

PMID- 21714406
TI  - Coming to a practice near you? Community-acquired meticillin resistant
      Staphylococcus aureus (CA-MRSA).
AB  - Hospital-acquired meticillin resistant Staphylococcus aureus (HA-MRSA) arose in
      the 1960s, but the last decade saw the emergence of a new entity: community
      acquired MRSA (CA-MRSA). Unlike HA-MRSA, patients affected by CA-MRSA have no
      obvious risk factors and may present with recurrent skin and soft tissue
      infections (SSTI) or, rarely, severe necrotizing pneumonia. This article provides
      an overview of CA-MRSA and reinforces the standard infection control procedures
      required to prevent further spread. CLINICAL RELEVANCE: The dental team require
      an awareness of emerging infections, their relevance to dentistry and the
      infection control procedures necessary to prevent transmission.

PMID- 21714407
TI  - Unexpected temporary mental nerve deficit after extraction of mandibular first
      molar: case report.
AB  - Temporary neurologic deficit affecting the distribution of the left mental nerve
      was reported in a warfarinized, diabetic patient who had a history of previous
      CVA with right-sided body weakness. The neurologic deficit was reported following
      routine extraction of a left mandibular first molar. Recovery of sensation began
      six weeks after the procedure. Possible mechanisms and preventive measures are
      discussed. CLINICAL RELEVANCE: The reader should understand that mental
      paraesthesia can be an unexpected outcome in the most routine of mandibular
      extractions.

PMID- 21714408
TI  - Coronectomy of third molar: a reduced risk technique for inferior alveolar nerve
      damage.
AB  - Causing damage to the inferior alveolar nerve (IAN) when extracting lower third
      molars is due to the intimate relationship between the nerve and the roots of the
      teeth. When the proximity radiologic markers between the IAN and the root of the
      third molars are present, the technique of coronectomy can be proposed as an
      alternative to extraction to minimize the risk of nerve injury, with minimal
      complications. CLINICAL RELEVANCE: Nerve injury after the extraction of the
      mandibular third molar is a serious complication. The technique of coronectomy
      can be proposed to minimize the risk.

PMID- 21714409
TI  - The 'secret' of success. Part 3.
AB  - Practice success is defined across the four 'dimensions' of oral health, patient
      satisfaction, job satisfaction and financial profit. It is suggested that the
      'secret' of success in dental practice is to make patient (customer) satisfaction
      the primary focus. Not a very earth shattering or surprising 'secret' perhaps!
      This is hardly a new idea, and not a concept restricted to dental practice. This
      principle applies to all businesses. This series of articles reviews evidence
      from across a broad spectrum of publications: from populist business publications
      through to refereed scientific papers, this 'secret' seems to be confirmed. The
      evidence for which aspects of our service are most important in achieving patient
      satisfaction (and therefore success) is explored. CLINICAL RELEVANCE: Good oral
      health outcomes for patients are defined as the primary purpose of dental
      practice and, therefore, an essential dimension of success. The link between
      positive patient perceptions of general care and his/her own oral health to
      practice success is explored.

PMID- 21714410
TI  - Oral cancer: comprehending the condition, causes, controversies, control and
      consequences. 6. Co-morbidities.

PMID- 21714411
TI  - Physical signs for the general dental practitioner. Case 84. Tuberous xanthomata.

PMID- 21714412
TI  - Beta-blocker therapy for valvular disorders.
AB  - Valvular disorders are common, and result in a neurohormonal milieu similar to
      the heart failure state. Although valve surgery is the therapy of choice in
      symptomatic severe lesions, many patients do not receive surgery for a variety of
      reasons. Beta-blockers have a role in the management of many patients with
      valvular disorders, especially in the case of patients with mitral stenosis,
      where they reduce the transmitral gradient. They may also serve as life-saving
      therapy in pregnant women with pulmonary edema. Other uses of beta-blockers
      include the reduction of valve-related hemolysis, the prevention of atrial
      fibrillation, and the relief of dynamic left and right ventricular outflow tract
      obstruction. The prevention of aortic root dilation, potentially with beta
      receptor blockade, may reduce the risk of aortic insufficiency in Marfan
      syndrome, and also in those with bicuspid aortic valves or following the Ross
      procedure. In this review, the potential role of beta-blockers is explored for
      the treatment of severe mitral and aortic regurgitation and asymptomatic severe
      aortic stenosis.

PMID- 21714413
TI  - Valve repair for rheumatic mitral regurgitation: still worthwhile?

PMID- 21714414
TI  - Rheumatic mitral valve repair: 22-year clinical results.
AB  - BACKGROUND AND AIM OF THE STUDY: Rheumatic mitral valve disease presents a
      surgical and a medical challenge to surgeons in the developing and developed
      world. Comprehensive reproducible repair techniques of the anatomic units in
      individual patients are required to restore the normal mitral valve anatomy and
      function. METHODS: Between April 1986 and December 2009, a total of 2,211
      patients underwent mitral valve repair at the authors' institution. Of these
      patients, 50 (32 women, 18 men) underwent repair at a median age of 45.6 years.
      Pure mitral stenosis was identified in four cases (8%), pure mitral regurgitation
      in 37 (74%), and mixed lesions in nine (18%). Posterior leaflet plication, Paneth
      posterior suture and autologous pericardial strip annuloplasty, chordal transfer
      and papillary muscle splitting were used to repair a rheumatically diseased
      mitral valve with leaflet prolapse, annulus dilatation and elongated or
      restricted chordae and malformed papillary muscle. RESULTS: Three deaths (6%)
      occurred in hospital (< or = 30 days), and 14 late deaths occurred between 60
      days and 14 years. The overall survival was 94.1 +/- 3.3%, 87.5 +/- 4.8%, 84.7 +/
      5.4%, 66.9 +/- 7.9% and 50.2 +/- 9.3% at 30 days and one, five, 10 and 15 years,
      respectively. Successful repair was achieved in 39 cases (78%). Actuarial freedom
      from severe mitral regurgitation and reoperation at one, five and 10 years was
      92.7 +/- 4.1%, 77.3 +/- 7.2% and 53.4 +/- 9.6%, respectively, and was 78% for
      Paneth posterior suture and autologous pericardial strip annuloplasty at five and
      10 years. The linearized rate for reoperation in the age groups < 20 years and >
      20 years was 4.5%/pt-yr (range: 2.0-10.2%/pt-yr) and 4.3%/pt-yr (range: 2.5
      7.2%/pt-yr), respectively. CONCLUSION: Mitral valve repair in rheumatic disease
      is feasible, but the results are suboptimal. Pure mitral incompetence may be
      reparable and long-lasting, whilst mixed lesions may be reparable but fail
      subsequently. The predictability of repair and long-term functional results was
      determined by perioperative echocardiographic evaluation and the application of
      an appropriate repair technique to treat the complex pathology of the mitral
      valve apparatus.

PMID- 21714415
TI  - Mitral valve repair versus replacement in the elderly population.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the available
      literature comparing mitral valve repair (MVRep) versus mitral valve replacement
      (MVR) in the elderly population, and to provide a pooled analysis regarding this
      issue. METHODS: Medline, Embase, Cochrane, trial registries, conference
      proceedings and reference lists were searched for trials of MVRep versus MVR
      surgery in the elderly population. The primary outcome was 30-day mortality,
      while secondary outcomes were postoperative complications and length of hospital
      stay. Pooled odds ratios were calculated for categorical outcomes and weighted
      mean differences for continuous outcomes. RESULTS: Four studies retrieved were
      deemed appropriate for inclusion. The outcome measures used for the analysis
      clearly showed a benefit of MVRep in the elderly population with reduced
      mortality (pooled Odds Ratio (OR) = 3.97; p = 0.003) and reduced postoperative
      complications (pooled OR = 2.35; p = 0.003). There was no significant difference
      between the two groups with regards to duration of hospital stay (weighted mean
      difference = 0.22; p = 0.18). CONCLUSION: With the demonstration of clear
      advantages of MVRep over MVR in the elderly population, a randomized trial
      between the two techniques is not ethically justifiable. As there are clear
      advantages to MVRep, it is recommended that this should be the primary treatment
      offered in mitral valve pathology, irrespective of the patient's age.

PMID- 21714416
TI  - Outcome and improvement predictors of mitral regurgitation after transcatheter
      aortic valve implantation.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral regurgitation (MR) is frequently present
      in patients with calcific aortic stenosis (AS). Yet, the issue of whether to
      surgically correct the MR during aortic valve replacement (AVR) remains
      uncertain. The study aim was to define the outcome of MR after transcatheter
      aortic valve implantation (TAVI) in the TRanscatheter EndoVascular Implantation
      of VALves (REVIVAL) II trial. METHODS: Echocardiography was performed before and
      at 24 h, and three and six months after valve implantation. The degree of MR was
      evaluated by expert readers and by the vena contracta (VC) method. Significant MR
      was defined as at least mild to moderate MR. Those patients with a 30% reduction
      in VC were classified as good responders (GR group), and the remainder as poor
      responders (PR group). RESULTS: The study comprised 35 subjects with at least
      mild to moderate MR before TAVI. The mean VC of the whole group declined from 0.5
      +/- 0.2 cm initially to 0.32 +/- 0.2 cm and 0.38 +/- 0.2 cm at 24 h and three
      months, respectively (p < 0.05). At three months, 12 patients had > 30% VC
      reduction; these constituted the GR group, while the remainder constituted the PR
      group. The percentage of patients with mitral annular calcification with
      restriction (MACr), defined as calcification encroaching onto the leaflets and
      restricting leaflet motion, was significantly lower in the GR group compared to
      the PR group (17% versus 61%, respectively; p < 0.05). The remaining pre
      specified parameters did not differ significantly between the GR and PR groups,
      including age, gender, mitral valve tethering height and area (6 +/- 2 mm versus
      5 +/- 3 mm and 10 +/- 4 mm2 versus 13 +/- 9 and 10 +/- 4 mm2, respectively),
      change in the aortic valve area (336 +/- 130% versus 285 +/- 180%), change in
      mean systolic aortic valve pressure (-20 +/- 8% versus - 23 +/- 10%), and left
      ventricular ejection fraction (47 +/- 15% versus 45 +/- 18%). CONCLUSION: MR is
      improved significantly after TAVI for AS. MACr was the only variable associated
      with a reduction in MR improvement. These results suggest that a careful
      echocardiographic evaluation of the mitral valve prior to TAVI may help to
      predict which patients should experience an improvement in their MR.

PMID- 21714417
TI  - Severe aortic stenosis: a neglected malignant disorder and strategies to improve
      outcomes.

PMID- 21714418
TI  - Prevalence and characteristics of unoperated patients with severe aortic
      stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Although aortic valve replacement (AVR) is the
      preferred therapy for severe symptomatic aortic stenosis (AS), a substantial
      number of patients with indications for surgery do not undergo AVR. The study aim
      was to address, at multiple geographic locations and practice settings, the
      prevalence of unoperated patients with severe AS, and to explore potential
      barriers to intervention. METHODS: The medical records at 10 centers of various
      size and geographic distribution were reviewed retrospectively to identify
      patients with clinically severe AS (echocardiography/Doppler mean gradient > or =
      40 mm Hg, effective orifice area < 1.0 cm2, or an overall interpretation of
      severe AS; and no clinical contradiction of severe AS). Demographic, clinical and
      outcomes data were recorded, including referral to a cardiothoracic surgeon
      (CTS), performance of AVR, and rationale when no AVR was performed. RESULTS: Of
      952 patients who met the criteria for clinically severe AS, 497 (52%) were
      referred to a CTS for evaluation for AVR; subsequently, 395 patients (41%)
      underwent AVR and 557 (59%) were unoperated. Trends were similar across the
      institutions. Symptoms were present in 666 (79%) of 842 patients with available
      data, including 296 of 340 (87%) operated patients and 370 of 502 (74%)
      unoperated patients. Those patients referred to a CTS were younger, more often
      male, had higher aortic valve gradients, and more often were symptomatic. The
      dominant reasons cited for not undergoing AVR were comorbidities or high
      operative risk, advanced age or limited life expectancy, asymptomatic status, and
      patient or family refusal. The one-year survival was 94 +/- 2% for operated
      patients, and 69 +/- 3% for unoperated patients (66 +/- 3% for unoperated
      symptomatic and 78 +/- 5% for unoperated asymptomatic patients). CONCLUSION: In
      this multicenter survey, only about one-half of the patients with severe AS were
      referred to a CTS, and only about 40% underwent AVR. Three-quarters of unoperated
      patients were symptomatic. Referral to a CTS appeared more likely in the setting
      of symptoms of angina rather than heart failure or syncope, and elevated
      echocardiographic gradient rather than low valve area. Many patients who likely
      could benefit from AVR do not undergo evaluation for the condition, and similar
      observations were made at multiple medical institutions.

PMID- 21714419
TI  - Predictors of rapid aortic dilatation in adults with a bicuspid aortic valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The role of atherosclerosis and atherosclerotic
      risk factors in predicting progressive aortic dilatation in patients with
      bicuspid aortic valve (BAV) is not well defined. The study aim was to assess the
      role of these risk factors in progressive aortic dilatation in patients with this
      condition. METHODS: Adult patients were identified with BAV who displayed rapid
      aortic dilatation, and the association of the condition with hemodynamic and
      atherosclerotic risk factors was assessed. By using the Dartmouth-Hitchcock and
      Hartford Hospital echocardiographic databases between 1997 and 2009, a total of
      135 patients with BAV and serial echocardiograms recorded at least one year apart
      were allocated to groups of rapid progressors (RP; n = 53) or slow progressors
      (SP; n = 82). Rapid aortic progression was defined as an annual rate of
      progression > or = 75th percentile at the sinus of Valsalva or ascending aorta
      level. Univariate atherosclerotic and hemodynamic variables that correlated with
      rapid aortic dilatation were analyzed, and independent predictors of rapid aortic
      dilatation identified. RESULTS: The RP group had higher mean random blood glucose
      levels, greater coronary artery disease, more tobacco use, and a higher National
      Heart, Lung and Blood Institute 10-year risk of developing coronary heart disease
      (10-year risk). An elevated 10-year risk of > 7% (OR 4.5; 95% CI 1.92-10.73),
      tobacco use (OR 5.05; 95% CI 1.51-16.86) and higher random blood glucose level
      (OR 1.01; 95% CI 1.002-1.03) were independent predictors of rapid aortic
      dilatation. CONCLUSION: In adults with BAV and non-dilated aortas at baseline, an
      elevated 10-year risk, tobacco use and hyperglycemia may serve as predictors of
      rapid aortic dilatation.

PMID- 21714420
TI  - Understanding the catheter-Doppler pressure gradient discrepancy in aortic
      stenosis.

PMID- 21714421
TI  - Low-flow severe aortic stenosis with preserved ejection fraction, N-terminal pro
      brain natriuretic peptide (NT-proBNP) and cardiovascular remodeling.
AB  - BACKGROUND AND AIM OF THE STUDY: Severe aortic stenosis (AS) with preserved
      systolic function may coexist with 'low flow' and a lower stroke volume (SV). As
      the mechanisms of this phenomenon are not fully understood, the study aim was to
      assess the cardiac and vascular mechanisms of 'low-flow' severe AS with a
      preserved left ventricular ejection fraction (LVEF). METHODS: Forty-four
      consecutive patients (mean age 69.7 +/- 7.6 years) with severe degenerative AS
      [mean effective orifice area (EOA) 0.7 +/- 0.3 cm2] and preserved LVEF (> 50%)
      were enrolled into the study, and allocated to two groups depending on their
      stroke volume index (SVI) (< 35 and > or = 35 ml/m2, respectively). The clinical
      data, N-terminal pro-brain natriuretic peptide (NT-proBNP) serum levels and
      ultrasound assessment of LV geometry and function [stroke work (SW), relative
      wall thickness (RWT)], AS severity, indices of systemic arterial hemodynamics
      [systemic arterial compliance (SAC), systemic vascular resistance (SVR)] and
      remodeling [flow-mediated dilatation (FMD), pulse wave velocity (PWV)], as well
      as valvuloarterial impedance (Z(va)) were analyzed for all study patients.
      RESULTS: Twenty-four patients (56%; 13 females, 11 males) had low-flow LV output,
      and 20 (44%; four females, 16 males) had a normal LV output. The mean NT-proBNP
      serum levels were comparable between the study groups. An analysis of LV
      remodeling and function revealed a lower LV end-diastolic volume (LVEDV; 85.5 +/-
      24.1 versus 160.4 +/- 60.9 ml, p = 0.001), LV end-systolic volume (LVESV; 40.3 +/
      18.5 versus 66.8 +/- 44.2 ml, p = 0.03), LV mass index (LVMI; 150.1 +/- 53.4
      versus 183.7 +/- 57.5 g/m2, p = 0.07) and SW (95.6 +/- 23.7 versus 183.2 +/- 50.6
      mmHg x ml, p < 0.0001) in the group with SVI < 35 ml/m2. The average RWT was
      higher in the group with SVI < 35 ml/m2 (48.7 +/- 14.8 versus 40.0 +/- 7.5, p =
      0.04). The indices of systemic arterial hemodynamics were significantly different
      between the groups: the SAC was lower, and the SVR and Z(va) were higher, in
      patients with SVI < 35 ml/m2 while FMD values were significantly greater in
      patients with SVI < 35 ml/m2 (11.85 +/- 6.4 versus 7.29 +/- 6.3%, p = 0.035).
      However, the brachial artery diameter (BAd) was smaller in the latter group, and
      no differences were found in the FMD x BAd index values. The PWV values were
      comparable in both study groups. CONCLUSION: The low-flow phenomenon in severe AS
      with preserved LVEF is related to smaller LV dimensions, LV concentric
      hypertrophy, and an increased systemic arterial afterload without differences in
      plasma NT-proBNP levels. 'Paradoxically' higher values of FMD observed in this
      population may be associated with a higher proportion of females and a smaller
      BAd.

PMID- 21714422
TI  - Thrombocytopenia after AVR.

PMID- 21714423
TI  - Thrombocytopenia after aortic valve replacement with the Sorin Freedom Solo
      prosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: Thrombocytopenia after implantation of the Sorin
      Freedom Solo (FS) stentless aortic bioprosthesis has been described previously.
      Thus, relevant data acquired at the authors' institution were analyzed. METHODS:
      A comparison of platelet counts was made in patients operated on between January
      and August 2008 following implantation of either the FS valve (n = 26) or a
      stented pericardial prosthesis (n = 238). Thrombocyte levels were measured before
      surgery and on days 0, 1, 2, 3, 5 and 7 after surgery; a comparison was made
      using absolute and hematocrit-adjusted platelet counts. Clinical adverse events
      were investigated in both groups, and a multivariate analysis was performed to
      identify predictors for the occurrence of thrombocytopenia. RESULTS: After
      implantation of the FS valve, the mean absolute and hematocrit-adjusted platelet
      counts were significantly lower on days 2, 3, 5 and 7 after surgery. An
      additional decrease occurred between days 1 and 3 after surgery, but this was not
      associated with any adverse clinical outcome. Independent determinants for
      thrombocytopenia were age and the type of aortic prosthesis. Postoperative
      echocardiography revealed lower gradients after FS valve implantation.
      CONCLUSION: Given the superior hemodynamic performance of the FS valve, and the
      absence of any adverse effects, implantation with this valve may be justified in
      selected patients. Further clarification of the mechanisms causing
      thrombocytopenia is required.

PMID- 21714424
TI  - Clinical and hemodynamic outcomes after aortic valve replacement with stented and
      stentless pericardial xenografts: a propensity-matched analysis.
AB  - BACKGROUND AND AIM OF THE STUDY: Pericardial aortic xenografts have demonstrated
      excellent durability, and also freedom from tissue failure and from endocarditis.
      The aim of this single-center propensity-matched study was to compare the
      clinical and hemodynamic results of aortic valve replacement (AVR) with that for
      stented and stentless pericardial bioprostheses. METHODS: A total of 111
      consecutive AVRs with the Perimount Magna stented valve, performed between
      December 2002 and December 2007, and 150 consecutive AVRs with the Pericarbon
      Freedom stentless bioprosthesis, performed between July 1999 and December 2007,
      was reviewed. Based on a propensity-score analysis, 81 matched pairs were
      created. The mean age of the 162 patients was 74 +/- 7 years. In total, 31 (38%)
      and 39 (48%) associated procedures were performed in the stented and stentless
      groups, respectively (p = 0.20). The mean follow up for stented-valve patients
      was 20 +/- 9 months (range: 6-35 months), and for stentless-valve patients was 36
      +/- 21 months (range: 6-83 months) (p < 0.05). RESULTS: The operative mortality
      was 4.9% (n = 4) and 6.2% (n = 5) (p = 0.77) in the stented- and stentless-valve
      groups, respectively. The cumulative actuarial freedom from structural valve
      deterioration, non-structural dysfunction, reoperation, prosthetic valve
      endocarditis, hemorrhage and thromboembolic events after 24 months were 98.4 +/-
      1.5% and 96.4 +/- 2.6% (p = 0.12) for the stented- and stentless-valve groups,
      respectively; the actuarial survival rates after 24 months were 82.6 +/- 5.2% and
      83.8 +/- 4.3% (p = 0.82), respectively, while freedom from valve-related death
      was 98.4 +/- 1.5% and 97.2 +/- 1.9% (p = 0.56), respectively. No statistically
      significant differences were identified between the peak and mean transaortic
      gradients. CONCLUSION: Both, the stented and stentless pericardial aortic
      xenografts provided good clinical and hemodynamic results. However, the study
      results failed to demonstrate any difference regarding early outcomes between the
      two groups.

PMID- 21714425
TI  - Hemodynamic performance of the St. Jude Medical Epic Supra aortic stented valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the hemodynamic
      performance of the St. Jude Medical Epic Supra bioprosthesis during the early six
      month follow up period, and to confirm the safety and efficacy of the valve by
      collecting details of adverse events and NYHA functional classification. METHODS:
      Fifty-seven patients undergoing aortic valve replacement (AVR) with the Epic
      Supra valve between September 2007 and January 2009 at three centers in Canada
      were evaluated for the study. The subjects were monitored preoperatively, at
      discharge, and at six months postoperatively. Echocardiographic data were
      available from 50 subjects at the six-month follow up. In order to prevent
      observer variability, all echocardiograms were sent to an independent
      Echocardiography Core Laboratory (ECL) for interpretation of the data. RESULTS:
      The mean subject age was 74 years. Concomitant coronary artery bypass grafting
      (CABG) was performed in 44% of the procedures. The mean pressure gradients were
      11.2, 12.5, 10.8, 8.4 and 11.3 mmHg, respectively, for valves sized 19 mm (n =
      2), 21 mm (n = 20), 23 mm (n = 22), 25 mm (n = 5) and 27 mm (n = 1). The average
      effective orifice areas (EOAs) were 1.44, 1.57, 1.69, 1.93 and 1.81 cm2 for the
      .valves sized 19, 21, 23, 25 and 27 mm, respectively. CONCLUSION: The results of
      the six-month echocardiographic follow up indicated that the Epic Supra valve
      offered excellent hemodynamic performance in the 21, 23 and 25 mm sizes. However,
      additional data are still required for the 19 and 27 mm valves to characterize
      their performance. The mean gradients and EOA-values were comparable to those of
      other supra-annular stented tissue valves. The EOA index indicated an absence of
      prosthesis-patient mismatch, with values in all subjects at or near 0.85 cm2/m2.
      The percentage of subjects without aortic insufficiency (AI) at follow up was
      92%; only four subjects showed trivial AI.

PMID- 21714426
TI  - The Ross full root replacement in adults with bicuspid aortic valve disease.
AB  - BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve disease (BAVD) is the most
      common congenital cardiac lesion causing aortic stenosis in adults. This lesion
      can be associated with a histological abnormality of the aortic wall and dilated
      or aneurysmal ascending aorta. In younger patients, the Ross operation offers
      several advantages over conventional aortic valve replacement (AVR); however, the
      rationale of performing this procedure on adults in the face of BAVD have been
      questioned. METHODS: Between 1994 and 2009, a total of 101 adult patients (mean
      age 36 years; range: 18-61 years) with BAVD underwent the Ross full root
      replacement at the authors' institution. Of these patients, 23 (23%) had an
      aneurysmal ascending aorta (4.0-5.2 cm) associated with BAVD which was resected
      at the time of, or subsequent to, a Ross AVR. The end point of the study was
      freedom from Ross autograft dilatation > 4.0 cm, dysfunction, or valve repair or
      replacement. RESULTS: The mean follow up was 6.0 +/- 3.9 years. At the latest
      follow up, 19 patients (19%) had a dilated ascending aorta with a mean size 45.1
      mm (range: 40-64 mm). Eight patients (8%) required a redo operation on the
      autograft. Three of seven patients undergoing reoperation had their autograft
      valve preserved; the remaining four underwent a modified Bentall root
      replacement. One patient had a repair of a left ventricular pseudoaneurysm below
      the Ross valve. Only three patients with preoperative ascending aorta dilation
      developed late autograft dilation. Freedom from autograft dilatation > 4.0 cm,
      dysfunction, repair or replacement was 80% at 10 years. CONCLUSION: Mid-term
      results indicate that Ross AVR in adults with BAVD had good outcomes, with a low
      incidence of autograft-related complications. In almost half of the patients
      undergoing reoperation, the autograft valve was preserved. The incidence of
      autograft valve insufficiency and dilatation might be further reduced by: (i)
      aggressively treating any postoperative systemic hypertension; (ii) externally
      fortifying the annulus and sinotubular junction of the autograft with Dacron
      strips; and/or (iii) replacing a dilated ascending aorta with a Dacron
      interposition graft. The preoperative diagnosis of BAVD and/or aneurysmal
      ascending aorta is not predictive of late autograft dilatation or failure.

PMID- 21714427
TI  - Right ventricular outflow tract reconstruction with decellularized porcine
      xenografts in patients with congenital heart disease.
AB  - BACKGROUND AND AIM OF THE STUDY: Decellularized xenogeneic pulmonary valves have
      been introduced for right ventricular outflow tract (RVOT) reconstruction in
      congenital heart disease. In the present study, the intermediate-term results
      from three institutions were analyzed. METHODS: Between January 2006 and
      September 2008, a total of 61 patients (median age 7 years; range: 9 days to 50
      years; median body weight 21 kg; range: 1.9-140 kg) underwent RVOT reconstruction
      with either the Matrix P (n = 9) or Matrix P Plus (n = 52) tissue-engineered
      conduit. Eighteen patients underwent surgery in infancy, and 31 patients had
      previously undergone one or more RVOT interventions or operations. RESULTS: The
      valve sizes ranged from 11 to 27mm. Five patients died during the hospital stay
      or within three months, from non-valve-related causes; hence, the early mortality
      was 8.2%. No deaths occurred during the follow up period. Reoperation due to
      valve failure became necessary in four patients; three patients underwent RVOT
      interventions due to distal anastomotic stenosis, and six reinterventions were
      performed distal to the valve due to hypoplastic branch pulmonary arteries.
      Patients with valve implantation during infancy showed a composite freedom from
      valve-related reoperation, catheter intervention or valve dysfunction (defined as
      dP(max) > 40 mmHg) of 87% at one and three years postoperatively. Both, computed
      tomography and magnetic resonance imaging studies demonstrated normal structural
      features, with no evidence of calcification. CONCLUSION: The Matrix P/Matrix Plus
      conduit represents a viable alternative for RVOT reconstruction in patients with
      congenital heart disease. The intermediate-term performance of the conduits was
      favorable compared to that of other currently available implants.

PMID- 21714428
TI  - Mitral and aortic valvular disease associated with benfluorex use.
AB  - Fenfluramine has been associated with an increased risk of pulmonary hypertension
      and valvular disease. Benfluorex is a fenfluramine derivative approved for the
      treatment of metabolic syndrome and type 2 diabetes mellitus. To date, only three
      isolated clinical cases of valvular disease and two recent case-control studies
      have been reported in patients exposed to benfluorex. Herein, the case is
      described of a patient with mitral and aortic valvular disease, with both
      echocardiographic and histopathological findings, who had been receiving
      benfluorex for several years, without any other etiology of valvular disease. The
      case is suggestive of toxic valvular lesions, similar to those observed
      previously during treatment with fenfluramine, pergolide, and cabergolide.

PMID- 21714429
TI  - Mitral valve perforation appearing years after radiofrequency ablation.
AB  - The case is reported of a young adult with Wolff-Parkinson-White (WPW) syndrome
      who, three years after a complicated radiofrequency (RF) catheter ablation
      procedure, developed dyspnea on exertion. Echocardiography revealed severe mitral
      valve regurgitation caused by a perforation of the posterior leaflet.
      Echocardiographic follow up is recommended after a complicated course of left
      sided catheter ablation.

PMID- 21714430
TI  - A case of Tropheryma whipplei infective endocarditis of the aortic and mitral
      valves in association with psoriatic arthritis and lumbar discitis.
AB  - Whipple's disease is a chronic condition that is characterized by diarrhea,
      weight loss and arthropathy, and caused by infection with the fastidious
      bacterium Tropheryma whipplei. Although once rare, Whipple's disease is being
      increasingly described owing mainly to advances in molecular genetics and an
      improved isolation of the organism. Whilst cardiac Whipple's disease occurs less
      commonly, especially in the absence of gastrointestinal symptoms, it has become
      apparent that some cases of culture-negative endocarditis may well be
      attributable to T. whipplei. The case is reported of a patient with Whipple's
      disease endocarditis in association with psoriatic arthritis and lumbar discitis.

PMID- 21714431
TI  - Large atrial myxoma causing mitral obstruction and severe pulmonary hypertension.
AB  - Myxoma is the most common type of cardiac tumor, accounting for 30-50% of all
      primary cardiac tumors. Clinically, patients usually present with at least one of
      the classic triad of obstructive cardiac, embolic, and constitutional signs. The
      case is reported of a large atrial myxoma in the left atrium which caused mitral
      valve obstruction, leading to severe pulmonary hypertension and right heart
      failure, mimicking rheumatic mitral stenosis. Postoperatively, a fall occurred in
      the patient's pulmonary artery pressure and she showed clinical improvement.

PMID- 21714432
TI  - Long-term immunesuppressive treatment of Pemphigus vulgaris as a predisposing
      factor for native valve endocarditis: report of two cases.

PMID- 21714433
TI  - Acute mitral regurgitation complicating transcatheter aortic valve implantation.

PMID- 21714435
TI  - The tiniest transplant. The great promise of stem cells is finally being put to
      the test.

PMID- 21714434
TI  - Bilateral carotid atherosclerosis: an inevitable consequence of homozygous
      familial hypercholesterolemia.

PMID- 21714436
TI  - Coping strategies and adherence to treatment in patients with type 2 diabetes
      mellitus.
AB  - INTRODUCTION: Diverse psychosocial and cultural factors are related to adherence
      to treatment of type 2 Diabetes mellitus (DM2) such as social support, coping
      styles and the cost of medical attention. OBJECTIVE: To study the influence of
      diverse psychosocial factors on adherence to treatment in patients with DM2.
      MATERIAL AND METHODS: In a cross sectional design we studied adherence to diet
      and medication, and its relationship with CS for diabetes, belief in conventional
      medicine, social support, and the perception of the burden of treatment cost on
      family finances. RESULTS: We included 210 patients a mean age of 56.3 years, 9.4
      years since diagnosis. Male DM patients had better adherence to medication
      (p<0.016) and social support (p<0.004), and higher rates for supportant CS (31.8
      vs. 29.0; p<0.009). Adherence to diet was associated with belief in conventional
      medicine (p<0.035) and marginally related to fatalistic CS (p<0.05). After
      testing social security coverage as dummy variable, a marginal association was
      found (p<0.15). Adherence to medication was associated with supportant CS
      (p<0.02) and marginally with avoidant CS (p<0.05). CONCLUSIONS: Supportant CS was
      more frequent in men. Belief in conventional medicine, and supportant CS were
      associated with adherence to treatment. These factors should be considered for a
      more rational approach for the management of disease.

PMID- 21714437
TI  - Cancer stem cells.
AB  - There are two hypotheses that explain tumor progression. The first one, the
      stochastic hypothesis, assumes that any cell within a tumor has the capacity to
      form and maintain the tumor mass. The second, the so-called hierarchical
      hypothesis, suggests the existence of a group of cells with a stem phenotype
      which, like in normal tissues, preserves tumors through a continuous production
      of progeny. These stem cells are in a particular niche, have a higher resistance
      to chemotherapy and radiotherapy, and are also capable of invading and migrating
      to other tissues. This review describes the cancer stem cells (CSCs), their
      function inside a tumor and the current knowledge about these cells.

PMID- 21714438
TI  - Early onset type 2 diabetes in Jamaica and in Mexico. Opportunities derived from
      an interethnic study.
AB  - Populations with Amerindian or African heritages are the one with the highest
      prevalence of diabetes worldwide. A large percentage of these individuals
      survived famine. However, the survival effect has become detrimental to their
      descendents living in an environment of caloric surplus. In countries, like
      Mexico and Jamaica, in which diabetes is highly prevalent, the onset of the
      disease happens at earlier ages. Our objective is to summarize diabetes data from
      Mexico and Jamaica and to discuss the opportunities that can result from an
      interethnic study. On one hand, the prevalence of diabetes in Jamaica is 17.9% in
      the 15+ age group. Jamaican researchers have built a cohort of families with
      early onset type 2 diabetes. In this population, this form of the disease is
      unrelated to MODY genes. On the other hand, the prevalence of diabetes in adult
      Mexicans is 14.4%. The group in which the greater percentual changes have
      occurred is the adults who are below the age of 40. More than two thirds of the
      early onset cases studied have a body mass index that is >25 kg/m2 and the
      clinical characteristics of metabolic syndrome. A minority of them has mutations
      in the MODY genes. The joint study of Mexican and Jamaican cohorts of early onset
      type 2 diabetes cases will be useful to identify new genetic and environmental
      players in the pathogenesis of this entity.

PMID- 21714439
TI  - Bad-mouthing gluten. What's behind the craze for gluten-free food?

PMID- 21714440
TI  - Disease hunter.

PMID- 21714441
TI  - The war over Lipitor.

PMID- 21714442
TI  - Does technology pay? Higher profits reported at IT-proficient hospitals.

PMID- 21714443
TI  - Paying for performance. Insurers expected to follow WellPoint's lead.

PMID- 21714444
TI  - We can have it all. ACOs can be driving force in health systems delivering
      quality care, low costs.

PMID- 21714446
TI  - State intervention. Leaders have opportunity to design own reform.

PMID- 21714445
TI  - Helping hand or big fist. Healthcare brass back strong federal role in reform
      despite chatter over state flexibility.

PMID- 21714447
TI  - States with the most health information exchanges. Based on ehealth initiative's
      map of health information exchange activity in the U.S.

PMID- 21714448
TI  - Thumbs down. ACO plans draw more criticism from top execs.

PMID- 21714449
TI  - VA to update VistA EHR.

PMID- 21714450
TI  - For everyone's benefit. Empower employees to set example of wellness in their
      communities.

PMID- 21714451
TI  - The doctor will see you now... at your office. Workplace clinics making a
      resurgence.

PMID- 21714452
TI  - In vitro evaluation of the permeation of cytotoxic drugs through reconstructed
      human epidermis and oral epithelium.
AB  - BACKGROUNDS: Occupational exposure to antineoplastic agents may represent a risk
      to health care workers, although the relevance of different exposure routes is
      not fully understood. The objectives of this study were to determine in vitro
      permeation of four widely used cytotoxic drugs (cisplatin, cyclophosphamide,
      doxorubicin, and fluorouracil) through two reconstituted tissue models
      representing human skin epidermis and oral mucosa. MATERIALS AND METHODS:
      Experiments were conducted with reconstructed models of human epidermis and oral
      epithelium, cultured in a chemically-defined medium under conditions simulating
      possible exposure scenarios (6 h duration, three concentrations corresponding to
      commonly used application doses). The amounts of drugs permeated through the
      tissues into the receptor media were determined using ultra performance liquid
      chromatography with photospectrometric detection. RESULTS: The highest epidermis
      permeations (P = 0.2 x 10(-3) - 1.5 x 10(-3) cm x h(-1)) were observed with three
      polar drugs (cisplatin, cyclophosphamide and fluorouracil), while permeation by
      more hydrophobic doxorubicin was minor (P(max) = 0.03 x 10(-3) cm x h(-1)). As
      expected, more pronounced tissue permeation was observed with the reconstructed
      oral epithelium having the maximum permeability coefficient (P = 180 x 10(-3) cm
      x h(-1)) for cisplatin and fluorouracil. Histological evaluation of the exposed
      tissues revealed cytotoxic effects at higher doses, especially for oral
      epithelium. CONCLUSION: Although the skin epidermis with keratinised stratum
      corneum provided relatively good protection, uptake (of at least some
      investigated drugs) via both types of tissue should not be underestimated. Our
      results provide basic experimental data on the skin and oral epithelia permeation
      for further modelling of exposure and health risk assessment.

PMID- 21714453
TI  - Congenital adrenal hyperplasia (CAH) a wolf in a rabbits' fur.

PMID- 21714454
TI  - Endogenous hyperandrogenism and exercise capacity lessons from the exercise
      congenital adrenal hyperplasia model.
AB  - Athletic excellence requires a combination of genetic endowment, continuous
      training, appropriate equipment, and proper nutrition. However, the specific
      genetic and/or intrinsic hormonal milieus that contribute to athletic performance
      are not clearly understood. Androgens are thought to play an important role in
      exercise-induced target tissue response. In adults, the use of exogenous anabolic
      steroids was found to improve athletic performance, decrease fatigue, increase
      muscle mass, and increase aggressiveness. However, the benefit of these
      substances in adolescents remains questionable. Moreover, the role of endogenous
      androgen secretion for competitive performance success is far less studied. The
      present review will summarize aspects related to the effect of endogenous
      hyperandrogenism on exercise performance, as seen in polycystic ovary syndrome
      (PCOS), and will concentrate on important lessons learned from the unique model
      of exercise in congenital adrenal hyperplasia, a disease associated with
      endogenous hyperandrogenism.

PMID- 21714455
TI  - A child with Cushing's syndrome--etiological clue from adrenal imaging (pediatric
      Cushing's syndrome).

PMID- 21714456
TI  - Polycystic ovaries and adrenal insufficiency in a young pubescent female with
      lipoid congenital adrenal hyperplasia due to splice mutation of the StAR gene: a
      case report and review of the literature.
AB  - We report a case of Lipoid Congenital Adrenal Hyperplasia (LCAH) secondary to
      Steroidogenic Acute Regulatory (StAR) gene mutation in an adolescent female with
      bilateral ovarian cysts. StAR gene defects follow an autosomal recessive mode of
      inheritance and typically present with severe adrenal insufficiency during
      infancy. Both sexes can be affected equally. XY males often present with sex
      reversal, while XX females may develop gonadal failure later in life due to
      premature loss of ovarian follicles. Recently there have been reported cases of
      successful fertility outcomes in women with LCAH. In our case report, we describe
      the clinical, biochemical and molecular analysis of a 16 year-old XX adolescent
      female who was suspected of having LCAH upon discovery of bilateral ovarian cysts
      in the context of adrenal insufficiency. Examination of the StAR gene revealed a
      homozygous splice site mutation. The patient is currently undergoing estradiol
      therapy to suppress ovarian cyst formation.

PMID- 21714457
TI  - Does fat fuel the fire: independent and interactive effects of genetic,
      physiological, and environmental factors on variations in fat deposition and
      distribution across populations.
AB  - Markers of inflammation (MOI) have been reported to influence bone health in
      adults, with reports of inverse associations. Adipose has also been linked to
      bone. In children, the interrelationships are unclear. The objective of this
      study was to evaluate the relationship between MOI (i.e. CRP, TNFR2, IL-6) and
      bone mineral content (BMC) and determine the contribution of fat
      deposition/distribution in children. Forty-nine children (59% male) 7-12 y
      participated. Body composition was evaluated by DXA, and MOI and insulin
      sensitivity (S(I)) were obtained during an IVGTT. Multiple linear regression was
      used for analyses. TNFR2 was inversely associated with BMC. In boys, TNFR2 was
      inversely associated with BMC, and in girls IL-6 was inversely associated with
      BMC, and total and percent fat influenced the relationships. Our results suggest
      a potential inhibitory role of inflammation on bone as well as a negative impact
      of adiposity. Future investigations are warranted to further investigate these
      relationships.

PMID- 21714458
TI  - Application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in
      screening of high risk children with inherited metabolic diseases in northern
      China.
AB  - OBJECTIVE: To investigate the morbidity and distribution of 35 inherited
      metabolic diseases in high risk children by LC-MS/MS in northern China. METHODS:
      The dry blood on filter papers, collected from 2760 children clinically suspected
      to have inherited metabolic diseases from more than sixty hospitals in north
      China, was tested by LC-MS/MS. The specimen was extracted out of the dry blood on
      filter paper, derivatized before being injected into LCMS/MS. The LC-MS/MS
      methodology used in the study was transferred from Pediatrix Medical Group (1301
      Concord Terrace, Sunrise, FL 33323), validated in our lab and further compared
      with United States CDC standard. The positive results were further confirmed by
      gas chromatography-mass, other laboratory tests and clinical symptoms. RESULTS:
      249 of the 2760 children (9%) were diagnosed with one or more of twenty-one
      disorders. Out of 249 patients, there are 41 (16.5%) fatty acid disorders, 71
      (28.5%) amino acid diseases, and 137 (55%) organic acidemias. 48 of the 249
      patients (19.3%) were neonates, including 11 (22.9%) with fatty acid disorders,
      15 (31.3%) with amino acid diseases, and 22 (45.8%) with organic acidemias. 201
      of the 249 patients were elder than 28 days, and was composed of 30 (14.9%) with
      fatty acid disorders, 56 (27.9%) with amino acid diseases, 115 (57.2%) with
      organic acidemias. CONCLUSIONS: The LC-MS/MS technology can be used to detect
      over 30 inherited metabolic disorders for Chinese pediatric clinic in a single
      collection of blood. The morbidity of IMD (9%) is relatively high among high risk
      children, thus we highly suggest that we shall provide initial screening of over
      30 IMDs for the high risk children in China using the technology of LC-MS/MS.

PMID- 21714459
TI  - Relationship between aminotransferases levels and components of the metabolic
      syndrome among multiethnic adolescents.
AB  - BACKGROUND: Data evaluating the frequency of elevated aminotransferases (as a
      surrogate for non-alcoholic fatty liver disease [NAFLD]) and metabolic syndrome
      (MS) components among overweight multiethnic children/adolescents originating
      predominantly from South/Central America and the Caribbean are limited. METHODS:
      A sample (N = 284) of multiethnic (75% Latino, 25% Afro Caribbean/non-Hispanic
      black) overweight children/ adolescents' (mean age 12.24 +/- 3.48) overnight
      fasting insulin and glucose, systolic/diastolic blood pressure, HDL/LDL/total
      cholesterol, triglyceride, aspartate aminotransferase (AST) and alanine
      aminostransferase (ALT) were analyzed. RESULTS: A total of 22% of the sample had
      elevated ALT (> or = 30 U/L; mean 25.94 U/L for Hispanics, 23.05 U/L for blacks)
      and 8% had elevated AST (> or = 35 U/L; mean 23.05 U/L for Hispanics, 24.68 U/L
      for blacks). AST and ALT were significantly correlated with triglycerides (r =
      0.23, P < .01; r = 0.18, P < .05, respectively) for the overall sample.
      CONCLUSIONS: Among overweight adolescents, MS components are associated with
      NALFD in subgroups of major ethnic groups suggesting that AST and ALT as
      surrogate markers for NAFLD should be included in addition to the standard cardio
      metabolic tests.

PMID- 21714460
TI  - Etiologies of precocious puberty: 15-year experience in a tertiary hospital in
      southern Thailand.
AB  - BACKGROUND: Precocious puberty (PP) is defined as the appearance of secondary sex
      characteristic at an age <8 years in girls and <9 years in boys, or menarche <9
      years in girls. OBJECTIVE: To determine the etiologies and clinical
      characteristics of children presenting with PP. SUBJECTS AND METHOD: The medical
      records of 307 children (292 girls, 15 boys) with PP (1995-2009) were reviewed.
      RESULTS: The most common etiology of PP in girls was premature thelarche (35.5%),
      followed by early puberty (25.4%) and central precocious puberty (23.8%). All
      boys had underlying pathologic etiologies. The average age of girls with
      premature thelarche was significantly younger than those with any other
      etiologies (2.8 +/- 1.6 vs 6.7 +/- 1.7 years, p <0.001). Height and weight SDSs
      of girls with central precocious puberty and early puberty were significantly
      greater than those with premature thelarche. CONCLUSIONS: The most common
      etiologies of PP in girls are premature thelarche in girls <6 years and early
      puberty in girls >6 years. PP in boys has to be investigated for underlying
      etiologies.

PMID- 21714461
TI  - Are IGF-I and IGF-BP3 useful for diagnosing growth hormone deficiency in children
      of short stature?
AB  - BACKGROUND: The diagnosis of growth hormone deficiency (GHD) is based on clinical
      and auxological characteristics combined with the results of growth hormone
      provocation tests. AIM: To evaluate the utility of IGF-I and IGF-BP3 serum levels
      in the diagnosis of GHD among children of short stature. SUBJECTS/METHODS: We
      recruited 207 short pre-pubertal children and divided them into two groups. One
      group consisted of 70 children (mean age 7.93 +/- 2.35 SD) with a growth hormone
      (GH) response on two provocative tests of < or = 8 ng/ml, while the other group
      contained 137 children (mean age 7.92 +/- 2.11 SD) with a peak GH value of > 8
      ng/ml. Serum IGF-1 and IGF-BP3 levels were determined in the two groups. RESULTS:
      The difference in serum IGF-I between the two groups was not significant (p=
      0.26), while the difference in IGF-BP3 between the two groups was statistically
      significant (p= 0.004). The performance of serum IGF-1 and IGF-BP3 as a
      diagnostic tool, expressed as AUC by ROC analyses, was quite low. CONCLUSION:
      Neither IGF-I nor IGF-BP3 are an adequate substitute for the stimulus test in the
      diagnosis of growth hormone deficiency among children of short stature.

PMID- 21714462
TI  - Testosterone, obesity and insulin resistance in young males: evidence for an
      association between gonadal dysfunction and insulin resistance during puberty.
AB  - OBJECTIVE: To assess the relationships among obesity, insulin sensitivity, and
      testosterone in pubertal boys. PARTICIPANTS: This study included 20 lean, obese,
      and type 2 diabetic (T2DM) males, the majority of whom underwent a
      hyperinsulinemic-euglycemic clamp (n=16). METHODS: Glucose disposal (M value),
      serum testosterone, and body mass index (BMI) z-score were measured. Differences
      in testosterone were evaluated by group (lean vs. obese vs. T2DM), while
      regression was performed to evaluate the relationships among testosterone,
      obesity and insulin sensitivity. RESULTS: Controlling for Tanner stage,
      testosterone concentration was significantly lower in obese (p=0.02) and T2DM
      males (p=0.001) compared to lean males. Furthermore, M value was significantly
      associated with serum testosterone, even after controlling for BMI and Tanner
      stage. CONCLUSIONS: These data suggest that obese adolescent boys have lower
      serum testosterone than controls of the same Tanner stage, and echo the data in
      adult males associating obesity and insulin resistance with hypogonadism.

PMID- 21714463
TI  - Effects of vitamin D receptor gene polymorphisms on susceptibility to disease and
      bone mineral density in Turkish patients with type 1 diabetes mellitus.
AB  - BACKGROUND: Vitamin D receptor (VDR) gene is regarded as one of the candidate
      genes for type 1 diabetes mellitus (T1D) susceptibility and of some genetic
      factors involved in the development of osteoporosis in this group. STUDY DESIGN:
      We characterized the VDR gene polymorphism (BsmI, ApaI, TaqI, FokI and Cdx-2
      binding site) in a group of Turkish patients with T1D (n=90) and correlated
      respective VDR genotypes with the bone mass and some parameters of bone turnover.
      RESULTS: There were no differences in the genotype frequencies of the BsmI, ApaI,
      TaqI and Cdx-2 polymorphisms in patients and control subjects. We found a
      significantly higher prevalence of the F allele/the FF genotype in the patients
      compared to controls (p=0,0031, odds 1.96 (1,27-3,01)). We observed no difference
      in markers of bone turnover (Serum levels of osteocalcin, PINP and alkaline
      phosphatase, urinary levels of calcium/ creatinine and N-telopeptid) among
      different VDR genotypes. No correlation was found between VDR polymorphisms and
      DEXA measurements of these patients. CONCLUSIONS: Although the FF genotype was
      found to be a risk factor in a Turkish population, elucidation of this result is
      necessary in other larger study groups drawn from the same ethnic population.

PMID- 21714464
TI  - Changes in dynamic insulin and gastrointestinal hormone secretion in obese
      children.
AB  - BACKGROUND: Disturbed satiety and hunger perception in obese individuals has been
      reported, however data on the dynamic changes of hormonal mediators are sparse.
      OBJECTIVE: To evaluate the secretion pattern of insulin, ghrelin, peptide-YY
      (PYY), and amylin via 0 to 180 min oral glucose tolerance testing in obese and
      lean children. SUBJECTS AND METHODS: A prospective clinical study was conducted
      on lean (n=9) and obese (n=20) Caucasian children of comparable age, gender, and
      pubertal stage. Serial blood samples were collected. RESULTS: Compared to
      baseline, levels of acylated ghrelin showed a significant decrease in lean
      (p<0.05) but not in obese children. PYY increase was blunted and of shorter
      duration (60 min) in obese children. Amylin levels increased in both groups, and
      attained significantly higher levels in obese children (p<0.05). CONCLUSION:
      Glucose stimulated gut hormone secretion differed between obese and lean
      children, and may explain the disturbed satiety observed in obese children.

PMID- 21714465
TI  - Risk factors for early onset of diabetic nephropathy in pediatric type 1
      diabetes.
AB  - AIM: Diabetic nephropathy (DN) is a frequent complication in patients with long
      standing type 1 diabetes mellitus (DM1). The objective of this study was to
      assess the prevalence of DN in DM1 patients diagnosed during childhood and its
      association with clinical and metabolic variables, such as age at diagnosis of
      DM1, glucose control, dyslipidemia, hypertension and the occurrence of diabetic
      retinopathy (DR). METHODS: The medical records of 205 patients admitted to the
      Pediatric Endocrinology Division at the Hospital das Clinicas da Universidade
      Federal de Minas Gerais, in Belo Horizonte, Brazil, were analyzed. For the
      analysis of survival and prognostic factors, the Kaplan-Meyer method and the COX
      regression model were used. RESULTS: The mean disease duration was 11.32 +/- 4.02
      years and the mean age at diagnosis was 6.10 +/- 3.54 years. Microalbuminuria was
      present in 11.2% of them, proteinuria in 6.8% and end-stage renal disease (ESRD)
      in 2.9%. There was a significant association between the occurrence of
      microalbuminuria or proteinuria and poor glucose control (p=0.025 and p=0.005,
      respectively), higher LDL cholesterol levels (p=0.006 and p=0.004, respectively)
      and age greater than 6 years at diagnosis (p=0.049 and p=0.05, respectively).
      Proteinuria was also associated to the occurrence of DR (p=0.016). CONCLUSION:
      Our data showed that the prevalence of DN was higher than expected in this young
      population studied, especially considering the most severe forms. Clinical and
      laboratory factors associated to ND were: poor long-term glucose control, higher
      levels of LDL-C, higher age at diagnosis and the occurrence of DR.

PMID- 21714466
TI  - High frequency of D727E polymorphisms in exon 10 of the TSHR gene in Brazilian
      patients with congenital hypothyroidism.
AB  - Congenital Hypothyroidism affects between 1:3000 and 1:4000 newborn infants in
      iodine-sufficient regions. Some studies have shown that mutations and
      polymorphisms in the TSH receptor gene are responsible for this disease. In the
      present study, mutations of exon 10 of the TSH receptor gene were investigated in
      Congenital Hypothyroidism patients. In the present study a sample of 90 Brazilian
      patients with primary congenital hypothyroidism was analyzed. Genomic DNA was
      isolated from peripheric blood samples. Exon 10 of the TSH receptor gene was
      amplified by PCR, and amplicons were automatically sequenced. Three nucleotide
      alterations were identified: c.1377G>A (A459A), c.1935G>A (L645L), and c.2181C>G
      (D727E). A459A polymorphism was also described previously in patients with
      thyroid cancer. The nucleotide alteration L645L was found in a single patient.
      This is the first time the L645L mutation has been described. D727E polymorphism
      showed high frequency (allele frequency 10%) in present study when compared to
      others reports.

PMID- 21714467
TI  - Two novel mutations of SRD5A2 gene in Indonesian siblings with clinical 5-alpha
      reductase deficiency.
AB  - Steroid 5-alpha-reductase 2 deficiency is an autosomal recessive disorder with
      clinical spectrum ranges from a male phenotype with hypospadia to a female
      phenotype with normal wolffian structures. Over 50 different mutations of SRD5A2
      gene has been described in affected patients and several mutations were detected
      in specific populations. DNAs of two 46,XY DSD Indonesian siblings, aged 13 and
      18 years old, with clinically suspected of 5-alpha-reductase deficiency and their
      mother were analysed for molecular defects of SRD5A2 gene. Different from other
      reports, in our series three mutations were found in each patient. Two novel
      mutations were detected in these patients and their mother, which are p.Gly34fs
      and c.699-1G>T. The other mutation detected was c.680G>A or p.Arg227Gln, which
      commonly described in Far East Asian population. Whether the p.Arg227Gln mutation
      is considered a polymorphism or a mutation in Indonesian population warrants
      further study.

PMID- 21714468
TI  - Serendipitous identification of Graves' disease in identical twins with
      polydipsia.
AB  - Graves' disease in adolescents and adults usually presents with classic symptoms
      including weight loss, frequent stools, irritability, and heat intolerance.
      However, the clinical manifestations of hyperthyroidism in young children are
      often subtle, unrecognized, and atypical. Here, we report a 6 year-old girl who
      presented for evaluation of increased. thirst. Review of systems was negative
      with respect to weight loss, irritability, palpitations, diarrhea, and school
      performance problems. Physical exam was unremarkable except for an enlarged
      thyroid gland. Her identical twin sister, who incidentally accompanied her to
      clinic, also had a previously unidentified goiter. Testing for diabetes was
      negative. Further laboratory investigation was consistent with Graves' disease in
      both girls. Polydipsia is a rare and unusual presenting feature of
      hyperthyroidism in children. The evolution of this case highlights the importance
      of maintaining a high index of suspicion for thyroid disease during childhood.

PMID- 21714469
TI  - The R450H mutation and D727E polymorphism of the thyrotropin receptor gene in a
      Chinese child with congenital hypothyroidism.
AB  - BACKGROUND: Congenital hypothyroidism (CH) is the most prevalent congenital
      endocrine disorder. The molecular cause of CH in the majority of newborns is
      unknown. The aim of this study was to investigate the mutation of thyrotropin
      receptor (TSHR) gene in Chinese children with congenital hypothyroidism (CH). and
      the hereditary characteristic. METHODS: Eighteen Chinese children with CH were
      enrolled for molecular analysis of the TSHR gene and 105 normal controls were
      evaluated. The exons 1-9, and 10 of TSHR gene were detected by PCR-SSCP (single
      stranded conformation polymorphism) and sequenced. RESULTS: A slower and a faster
      mobility SSCP shift showed in a 12-year old child with hypoplasic gland.
      Sequencing of TSHR gene revealed a homozygous mutation (CGC --> CAC, Arg450His)
      and a polymorphism (GAC --> GAG, Asp727Glu). The controls revealed no variants.
      The 12 relatives of the proband were enrolled and investigated. Six relatives,
      including his mother and father, were heterozygous for R450H mutation and D727E
      polymorphism of the TSHR gene. Thyroid hormone levels were normal except for
      circulating TSH (5.96-6.92 mU/L) level slightly elevated in six heterozygous
      family members. CONCLUSIONS: Homozygous mutation R450H of the TSHR gene led to
      CH. Heterozygous mutation R450H was the cause of subclinical hypothyroidism.

PMID- 21714470
TI  - Incidental finding of idiopathic unilateral adrenal calcification in an 18-month
      old child: case report and review of the literature.
AB  - The presence of calcified lesions in the adrenal gland requires a careful
      endocrine, microbiological and radiological evaluation combined with detailed
      clinical history to confirm its non-evolving nature and avoid unnecessary
      surgery. We report an 18-month-old male child hospitalized with an incidentally
      discovered calcification in his right adrenal gland. All biochemical data as well
      as liver, renal and adrenal function tests were normal. Abdominal computed
      tomography scan showed that the right adrenal gland was completely occupied by a
      large calcification, which was put in relationship with an undetected adrenal
      distress during the neonatal period, as macrosomy and clavicle fracture of the
      newborn could let us suggest. Our report describes the diagnostic approach to
      disclose the nature of a suprarenal mass, which is particularly problematic when
      this is found incidentally. In addition, an extensive review of the medical
      literature dealing with non-traumatic adrenal calcifications and haemorrhages in
      children has been carried out.

PMID- 21714471
TI  - SEAIC-SEORL. Consensus Document on Nasal Polyposis. POLINA Project.

PMID- 21714472
TI  - Do calcium supplements raise cardiovascular risk?

PMID- 21714473
TI  - Diagnosing and managing psychosis in primary care.
AB  - Psychosis is broadly defined as the presence of delusions and hallucinations. It
      can be organic or functional. The former is secondary to an underlying medical
      condition, such as delirium or dementia, the latter to a psychiatric disorder,
      such as schizophrenia or bipolar disorder. The identification and treatment of
      psychosis is vital as it is associated with a 10% lifetime risk of suicide and
      significant social exclusion. Psychosis can be recognised by taking a thorough
      history, examining the patient's mental state and obtaining a collateral history.
      The history usually enables a distinction to be made between bipolar disorder,
      schizophrenia and other causes. Early symptoms often include low mood, declining
      educational or occupational functioning, poor motivation, changes in sleep,
      perceptual changes, suspiciousness and mistrust. The patient's appearance, e.g.
      unkempt or inappropriately attired, may reflect their predominant mental state.
      There may be signs of agitation, hostility or distractibility. Speech may be
      disorganised and difficult to follow or there may be evidence of decreased
      speech. Mood may be depressed or elated or change rapidly. Patients may describe
      abnormal thoughts and enquiry into thoughts of suicide should be routine.
      Disturbances of thought such as insertion or withdrawal may be present along with
      perceptual abnormalities i.e. illusions, hallucinations. Insight varies during
      the course of a psychotic illness but should be explored as it has implications
      for management. All patients presenting with first episode psychosis for which no
      organic cause can be found should be referred to the local early intervention
      service. In patients with a known diagnosis consider referral if there is: poor
      response or nonadherence to treatment; intolerable side effects; comorbid
      substance misuse; risk to self or others.

PMID- 21714474
TI  - Raising standards of care for patients with depression.
AB  - The point prevalence rates for ICD-10 depressive episode and ICD-10 mixed anxiety
      and depressive disorder were 2.3% and 9.0% respectively, according to the 2007
      household survey of adult psychiatric morbidity in England. Adults in the UK with
      these diagnoses were estimated to have taken more than a quarter of the total
      number of days' sickness absence in one year. Few patients receive effective
      treatment and between one- and two-thirds of primary care patients with major
      depression have not fully recovered 12 months later. The NHS Outcomes Framework
      has identified 'Enhancing quality of life for people with mental illness' as a
      key improvement area. The NICE quality standard on depression in adults is
      intended to facilitate this by providing a definition of high quality care. If
      the standard is followed, patients will benefit from: reduced prescribing of
      antidepressants to those who will not benefit; increased access to psychological
      interventions; increased support through structured monitoring and active follow
      up and reduced risk of chronic relapsing depression. People who may have
      depression should receive an assessment that identifies the severity of symptoms,
      the degree of associated functional impairment and the duration of the episode.
      Health outcomes at each appointment should be recorded and the findings used to
      adjust delivery of interventions.

PMID- 21714475
TI  - Identifying the culprit allergen in seasonal allergic rhinitis.
AB  - Seasonal allergic rhinitis (SAR) is the main form of rhinitis in children whereas
      in adults it accounts for about a third of cases of rhinitis. It is a risk factor
      for the development of asthma and chronic rhinosinusitis. The most common
      allergic triggers are grass and tree pollens, allergy to moulds and weeds is less
      common. Identifying the months of the year when an individual is symptomatic will
      help define the culprit allergen. If there is a clear recurring seasonal history
      the diagnosis may be made on the strength of the history. Skin prick tests are
      available in specialist clinics and are a useful tool in differentiating SAR from
      non-allergic rhinitis and defining the culprit allergen(s). Specific IgE tests
      for suspected allergens can be performed if skin tests are not available. A
      positive specific IgE test to an allergen does not necessarily mean that clinical
      allergy is present, it may reflect sensitisation of the immune system. Although,
      in general, specific IgE tests have a high negative predictive value they are
      less sensitive than skin prick tests for grass pollen and moulds. Allergen
      avoidance is the first step in the management of any allergic rhinitis. Oral non
      sedating antihistamines are recommended as first-line treatment for mild SAR,
      higher doses may be necessary in moderate to severe SAR. Intranasal
      corticosteroids should be used in moderate to severe forms of SAR and also in
      mild forms where treatment with antihistamines has failed. There are no major
      differences in terms of efficacy between different corticosteroid preparations.
      Long-term growth studies in children using fluticasone, mometasone and budesonide
      (but not beclometasone) have been reassuring.

PMID- 21714476
TI  - Skin signs associated with systemic disease.

PMID- 21714477
TI  - Breast milk: vomiting and diarrhoea. 1911.

PMID- 21714478
TI  - Listen to your patients.

PMID- 21714480
TI  - A general organocatalyzed Michael-Michael cascade reaction generates
      functionalized cyclohexenes.
AB  - Although beta-dicarbonyl compounds are regularly employed as Michael donors,
      intermediates arising from the Michael addition of unsaturated beta-ketoesters to
      alpha,beta-unsaturated aldehydes are susceptible to multiple subsequent reaction
      pathways. We designed cyclic unsaturated beta-ketoester substrates that enabled
      the development of the first diphenyl prolinol silyl ether catalyzed Michael
      Michael cascade reaction initiated by a beta-dicarbonyl Michael donor to form
      cyclohexene products. The reaction conditions we developed for this Michael
      Michael cascade reaction were also amenable to a variety of linear unsaturated
      beta-ketoester substrates, including some of the same linear unsaturated beta
      ketoester substrates that were previously ineffective in Michael-Michael cascade
      reactions. These studies thus revealed that a change in simple reaction
      conditions, such as solvent and additives, enables the same substrate to undergo
      different cascade reactions, thereby accessing different molecular scaffolds.
      These studies also culminated in the development of a general organocatalyzed
      Michael-Michael cascade reaction that generates highly functionalized
      cyclohexenes with up to four stereocenters, in up to 97% yield, 32:1 dr, and 99%
      ee, in a single step from a variety of unsaturated beta-ketoesters.

PMID- 21714479
TI  - Progression of cancer from indolent to aggressive despite antigen retention and
      increased expression of interferon-gamma inducible genes.
AB  - Many cancers escape host immunity without losing tumor-specific rejection
      antigens or MHC class I expression. This study tracks the evolution of one such
      cancer that developed in a mouse following exposure to ultraviolet light. The
      primary autochthonous tumor was not highly malignant and was rejected when
      transplanted into naive immunocompetent mice. Neoplastic cells isolated from the
      primary tumor were susceptible to the growth-inhibitory effects of IFNgamma in
      vitro, but expressed very low levels of MHC I antigen and were resistant to tumor
      specific T cells unless they were first exposed to IFNgamma. Serial passage of
      the primary tumor cells in vivo led to a highly aggressive variant that caused
      fast-growing tumors in normal mice. In vitro, the variant tumor cells showed
      increased resistance to the growth-inhibitory effects of IFNgamma but expressed
      high levels of immunoproteasomes and MHC I molecules and were susceptible to
      tumor-specific T cells even without prior exposure to IFNgamma.

PMID- 21714481
TI  - Effect of stereogenic centers on the self-sorting, depolymerization, and
      atropisomerization kinetics of porphyrin-based aggregates.
AB  - We present our results on the mixing of different porphyrin molecules in
      supramolecular assemblies. Herein, chiral amplification experiments reveal the
      subtle role of the structural (mis)match between these monomers. We show that
      according to the "sergeant-and-soldiers" principle, a chiral porphyrin "sergeant"
      efficiently mixes with achiral "soldiers" in the same helical aggregate and
      strongly biases its handedness. However, when we mix two porphyrin enantiomers in
      a majority-rules experiment, no chiral amplification is observed at all, which is
      due to their narcissistic self-sorting into conglomerate-like aggregates. The
      mixing between two enantiomers in the same stack only occurs in a diluted
      majority-rules experiment, in which enantiomeric mixtures of sergeants are
      diluted with achiral soldiers. The different outcomes of these chiral
      amplification phenomena are verified by modeling studies that reveal high
      mismatch penalties, which are ascribed to the high stereocenter loading of 12
      methyl groups onto the monomers. Mixed-metal chiral amplification experiments
      between copper- and zinc-porphyrins show the same distinction in their mixing
      behavior, which is further supported by fluorescence measurements. The selective
      removal of chiral Zn-porphyrins from these mixed-metal systems is performed with
      the Lewis base quinuclidine that depolymerizes the Zn-porphyrins upon axial
      ligation. This extraction process proceeds at different time scales, depending on
      the mixed state: slow extraction kinetics for the mixed sergeant-and-soldiers and
      diluted-majority-rules systems and an instant extraction for the phase-separated
      majority-rules system. By simultaneously monitoring the supramolecular chirality
      during extraction, a chiral memory effect is observed for both mixed systems that
      show slow extraction kinetics. For the sergeant-and-soldiers system, the
      remaining supramolecular backbone contains achiral monomers only, which give rise
      to a long lasting chiral memory with slow, entropy-driven atropisomerization. Yet
      in case of the diluted-majority-rules system, the remaining backbone contains a
      mixture of achiral and chiral monomers in its unpreferred helicity; giving rise
      to a short chiral memory, in which the fast atropisomerization is enthalpy-driven
      due to the high mismatch penalty.

PMID- 21714482
TI  - Indium-sulfur supertetrahedral polymers integrated with [M(phen)3]2+ cations (M =
      Ni and Fe).
AB  - A series of supertetrahedral polymers of chalcogenometalates (T3 cluster
      compounds) integrated with M-phen complexes (phen =1,10-phenanthroline; M = Ni,
      Fe) was prepared by a similar solvothermal technique. Compound
      [Fe(phen)(3)](4)[H(4)In(20)S(38)].Hphen.3HDMA.8H(2)O (Mp-InS-4) (DMA =
      dimethylamine) is a 1-D straight chain. Compounds
      [M(phen)(3)](4)[In(20)S(37)].6Hphen.4H(2)O (M = Ni, Mp-InS-5; Fe, Mp-InS-6) are
      the first reported 2-D Tn polymers integrated with complex cations of
      [M(phen)(3)](2+). Compound [Ni(phen)(3)](4)[H(4)In(20)S(38)].2Hphen.2HDMA.3H(2)O
      (Mp-InS-7) shows a zigzag 1-D structure. We find that the reaction time is an
      important factor in assembling of the T3 clusters. Prolonging the reaction time
      seems favorable to the higher condensed phases (from 0-D to 2-D). However, a
      longer reaction time resulted in the crack of 2-D structure. Integrating M-phen
      complex cations with the chalcogenido anions can improve absorption of the
      materials in the visible range due to the charge transfers within the cations or
      between cations and anions.

PMID- 21714483
TI  - RNA folding pathways and the self-assembly of ribosomes.
AB  - Many RNAs do not directly code proteins but are nonetheless indispensable to
      cellular function. These strands fold into intricate three-dimensional shapes
      that are essential structures in protein synthesis, splicing, and many other
      processes of gene regulation and expression. A variety of biophysical and
      biochemical methods are now showing, in real time, how ribosomal subunits and
      other ribonucleoprotein complexes assemble from their molecular components.
      Footprinting methods are particularly useful for studying the folding of long
      RNAs: they provide quantitative information about the conformational state of
      each residue and require little material. Data from footprinting complement the
      global information available from small-angle X-ray scattering or cryo-electron
      microscopy, as well as the dynamic information derived from single-molecule
      Forster resonance energy transfer (FRET) and NMR methods. In this Account, I
      discuss how we have used hydroxyl radical footprinting and other experimental
      methods to study pathways of RNA folding and 30S ribosome assembly.  Hydroxyl
      radical footprinting probes the solvent accessibility of the RNA backbone at each
      residue in as little as 10 ms, providing detailed views of RNA folding pathways
      in real time. In conjunction with other methods such as solution scattering and
      single-molecule FRET, time-resolved footprinting of ribozymes showed that stable
      domains of RNA tertiary structure fold in less than 1 s. However, the free energy
      landscapes for RNA folding are rugged, and individual molecules kinetically
      partition into folding pathways that lead through metastable intermediates,
      stalling the folding or assembly process.  Time-resolved footprinting was used to
      follow the formation of tertiary structure and protein interactions in the 16S
      ribosomal RNA (rRNA) during the assembly of 30S ribosomes. As previously observed
      in much simpler ribozymes, assembly occurs in stages, with individual molecules
      taking different routes to the final complex. Interactions occur concurrently in
      all domains of the 16S rRNA, and multistage protection of binding sites of
      individual proteins suggests that initial encounter complexes between the rRNA
      and ribosomal proteins are remodeled during assembly.  Equilibrium footprinting
      experiments showed that one primary binding protein was sufficient to stabilize
      the tertiary structure of the entire 16S 5'-domain. The rich detail available
      from the footprinting data showed that the secondary assembly protein S16
      suppresses non-native structures in the 16S 5'-domain. In doing so, S16 enables a
      conformational switch distant from its own binding site, which may play a role in
      establishing interactions with other domains of the 30S subunit. Together, the
      footprinting results show how protein-induced changes in RNA structure are
      communicated over long distances, ensuring cooperative assembly of even very
      large RNA-protein complexes such as the ribosome.

PMID- 21714484
TI  - Redox potentials of oxoiron(IV) porphyrin pi-cation radical complexes:
      participation of electron transfer process in oxygenation reactions.
AB  - The oxoiron(IV) porphyrin pi-cation radical complex (compound I) has been
      identified as the key reactive intermediate of several heme enzymes and synthetic
      heme complexes. The redox properties of this reactive species are not yet well
      understood. Here, we report the results of a systematic study of the
      electrochemistry of oxoiron(IV) porphyrin pi-cation radical complexes with
      various porphyrin structures and axial ligands in organic solvents at low
      temperatures. The cyclic voltammogram of (TMP)Fe(IV)O, (TMP = 5,10,15,20
      tetramesitylporphyrinate), exhibits two quasi-reversible redox waves at E(1/2) =
      0.88 and 1.18 V vs SCE in dichloromethane at -60  degrees C. Absorption spectral
      measurements for electrochemical oxidation at controlled potential clearly
      indicated that the first redox wave results from the
      (TMP)Fe(IV)O/[(TMP(+*))Fe(IV)O](+) couple. The redox potential for the
      (TMP)Fe(IV)O/[(TMP(+*))Fe(IV)O](+) couple undergoes a positive shift upon
      coordination of an anionic axial ligand but a negative shift upon coordination of
      a neutral axial ligand (imidazole). The negative shifts of the redox potential
      for the imidazole complexes are contrary to their high oxygenation activity. On
      the other hand, the electron-withdrawing effect of the meso-substituent shifts
      the redox potential in a positive direction. Comparison of the measured redox
      potentials and reaction rate constants for epoxidation of cyclooctene and
      demethylation of N,N-dimethylanilines enable us to discuss the details of the
      electron transfer process from substrates to the oxoiron(IV) porphyrin pi-cation
      radical complex in the oxygenation mechanisms.

PMID- 21714485
TI  - The heterogeneous nature of Cu2+ interactions with Alzheimer's amyloid-beta
      peptide.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive cognitive and memory impairment. Within the brain, senile plaques,
      which comprise extracellular deposits of the amyloid-beta peptide (Abeta), are
      the most common pathological feature of AD. A high concentration of Cu(2+) is
      found within these plaques, which are also areas under oxidative stress.
      Laboratory work has shown that in vitro Abeta will react with Cu(2+) to induce
      peptide aggregation and the production of reactive oxygen species. As such, this
      interaction offers a possible explanation for two of the defining pathological
      features observed in the AD brain: the presence of amyloid plaques, which consist
      largely of insoluble Abeta aggregates, and the abundant oxidative stress therein.
      Researchers have accordingly put forth the "metals hypothesis" of AD, which
      postulates that compounds designed to inhibit Cu(2+)/Abeta interactions and
      redistribute Cu(2+) may offer therapeutic potential for treating AD. 
      Characterization of the pH-dependent Cu(2+) coordination of Abeta is fundamental
      to understanding the neurological relevance of Cu(2+)/Abeta interactions and
      aiding the design of new therapeutic agents. In an effort to shed light on the
      problem, many experimental and theoretical techniques, using a variety of model
      systems, have been undertaken. The preceding decade has seen numerous conflicting
      spectroscopic reports concerning the nature of the Cu(2+)/Abeta coordination. As
      the number of studies has grown, the nature of the pH-dependent ligand
      environment surrounding the Cu(2+) cation has remained a point of contention. In
      large part, the difficulties can be attributed to inappropriate choices of the
      model system or to methods that are incapable of quantitatively delineating the
      presence and identity of multiple Cu(2+) coordination modes.  Electron
      paramagnetic resonance (EPR) is the method of choice for studying paramagnetic
      metal-protein interactions. With the introduction of site-specific (15)N, (17)O,
      and (13)C isotopic labels and the application of advanced techniques, EPR is
      capable of eliminating much of the ambiguity. Recent EPR studies have produced
      the most definitive picture of the pH-dependent Cu(2+) coordination modes of
      Abeta and enabled researchers to address the inconsistencies present in the
      literature.  In this Account, we begin by briefly introducing the evidence for a
      role of Cu(2+) in AD as well as the potential physiological and therapeutic
      implications of that role. We then outline the EPR methodology used to resolve
      the molecular details of the Cu(2+)/Abeta interactions. No drugs are currently
      available for altering the course of AD, and existing therapies only offer short
      term symptomatic relief. This focused picture of the role of Cu(2+) in AD-related
      plaques offers welcome potential for the development of new methods to combat
      this devastating disease.

PMID- 21714486
TI  - Silylation-based kinetic resolution of monofunctional secondary alcohols.
AB  - The nucleophilic small molecule catalyst (-)-tetramisole was found to catalyze
      the kinetic resolution of monofunctional secondary alcohols via enantioselective
      silylation. Optimization of this new methodology allows for selectivity factors
      up to 25 utilizing commercially available reagents and mild reaction conditions.

PMID- 21714487
TI  - In-water dehydrative alkylation of ammonia and amines with alcohols by a
      polymeric bimetallic catalyst.
AB  - An in-water dehydrative alkylation with a novel heterobimetallic polymeric
      catalyst is described. Thus, a boron-iridium heterobimetallic polymeric catalyst
      was prepared by ionic convolution of a poly(catechol borate) and an iridium
      complex. The alkylation of ammonia and amines with alcohols, alkylating agents,
      was performed with 1 mol % Ir of the heterogeneous catalyst in water without the
      use of organic solvents under aerobic conditions to give the corresponding
      alkylated amines.

PMID- 21714488
TI  - Synthesis and characterization of neutral luminescent diphosphine pyrrole- and
      indole-aldimine copper(I) complexes.
AB  - Heteroleptic copper(I) complexes of the types [Cu(N,N)(P,P)] and [Cu(N,O)(P,P)],
      where (P,P) = phosphine (PPh(3)) or diphosphine (dppb, DPEPHOS, XANTPHOS), (N,N)
      = pyrrole-2-phenylcarbaldimine, 2PyN: [Cu(2PyN)(PPh(3))(2)] (1), [Cu(2PyN)
      (dppb)] (2), [Cu(2PyN)(DPEPHOS)] (3), and [Cu(2PyN)(XANTPHOS)] (4), (N,N) =
      indole-2-phenylcarbaldimine, 2IndN: [Cu(2IndN)(DPEPHOS)] (8), and (N,O) = pyrrole
      2-carboxaldehyde, 2PyO: [Cu(2PyO)(DPEPHOS)] (5), [Cu(2PyO)(XANTPHOS)] (6), or
      (N,O) = indole-2-carboxaldehyde, 2IndO: [Cu(2IndO)(DPEPHOS)] (7), were
      synthesized and characterized by multinuclear NMR spectroscopy, electronic
      absorption spectroscopy, fluorescence spectroscopy, and X-ray crystallography (1
      3, 5-8). The complexes with aldimine ligands are thermally stable, and
      sublimation of 2-4 was possible at T = 230-250  degrees C under vacuum. All
      complexes exhibit long-lived emission in solution, in the solid state, and in
      frozen glasses. The excited states have been assigned as mixed intraligand and
      metal-to-ligand charge transfer (3)(MLCT + pi-pi*) transitions through analysis
      of the photophysical properties and DFT calculations on representative examples.

PMID- 21714489
TI  - Catalytic asymmetric addition of thiols to nitrosoalkenes leading to chiral non
      racemic alpha-sulfenyl ketones.
AB  - The first asymmetric organocatalytic sulfenylation of in situ derived
      nitrosoalkenes leading to chiral nonracemic alpha-sulfenylated ketones is
      described. The transformation proceeds in an umpolung fashion, relative to
      enolate/azaenolate methods, and uses simple thiols, thereby obviating the need
      for electrophilic sulfur reagents.

PMID- 21714490
TI  - Strategy for the rational design of asymmetric triply bridged dinuclear 3d-4f
      single-molecule magnets.
AB  - Three triply bridged M(II)-Dy(III) dinuclear complexes, [Ni(MU-L)(MU
      OAc)Dy(NO(3))(2)] 1, [Zn(MU-L)(MU-OAc)Dy(NO(3))(2)] 2, and [Ni(MU-L)(MU
      NO(3))Dy(NO(3))(2)].2CH(3)OH 3 were prepared with a new and flexible
      compartmental ligand, N,N',N"-trimethyl-N,N"-bis(2-hydroxy-3-methoxy-5
      methylbenzyl)diethylene triamine (H(2)L), containing N(3)O(2)-inner and O(4)
      outer coordination sites. These complexes have diphenoxo/acetate (1 and 2) or
      diphenoxo/nitrate (3) asymmetric bridging fragments. Compounds 1 and 3 exhibit
      ferromagnetic interaction between Ni(2+) and Dy(3+) ions and frequency dependence
      of the out-of-phase (chi"(M)) alternating current (ac) susceptibility signal
      characteristic of single-molecule-magnet behavior. The energy barriers Delta/k(B)
      for compound 3 under zero and 1000 Oe applied direct current (dc) magnetic fields
      were estimated from the Arrhenius plots to be 7.6 and 19.1 K, respectively.

PMID- 21714491
TI  - Microwave versus traditional solvothermal synthesis of Ni7(II) discs: effect of
      ligand on exchange reaction in solution studied by electrospray ionization-mass
      spectroscopy and magnetic properties.
AB  - A comparative evaluation of the solvothermal method of synthesis of magnetic
      Ni(7) discs with four different ligands using the same concentrations of reagents
      and temperature found microwave heating is more effective than the traditional
      oven one. Where the former only needs minutes, the latter needs days with an
      equivalence of 10 min microwave to 1 day of traditional. The size of crystals has
      a narrow distribution and increases with time for the microwave but is a rather
      wide distribution for the traditional one. Furthermore the shape of the crystals
      is more regular for the microwave. The four Ni(7)(II) discs of formulas
      [Ni(7)L(6)(MU(3)-OMe)(6)](ClO(4))(2) (1-3) and {[Ni(7)(L(4))(6)(MU(3)
      OMe)(6)][Ni(L(4))(2)]}(ClO(4))(2) (4) were synthesized as green hexagonal rods
      from Ni(ClO(4))(2).6H(2)O in mixed MeOH/MeCN solution and salicylalde Schiff base
      ligands (L(1) = 2-methoxy-6-(iminomethyl)phenol, L(2) = 2-ethoxy-6
      (iminomethyl)phenol, L(3) = 2-methoxy-6-((methylimino)methyl)phenol, L(4) = 2
      ethoxy-6-((methylimino)methyl)phenol). X-ray structural analyses show six
      symmetrically positioned Ni(2) around a central Ni(1) bridged by the MU(3)
      methoxide and surrounded by the ligand L which also isolates the discs from one
      another. The perchlorate sits in the interstices, and the planar [Ni(L(4))(2)] of
      4 also inserts itself between the discs. The structures of 1-3 can be regarded as
      ordered discotic liquid crystals. Electrospray ionization mass spectrometry of
      solutions showed an exchange of methoxide for hydroxide and a different
      distribution of [Ni(7)] phase with mixed (MeO/OH) core bridges, confirming a
      probable "step by step" substitution of MeO(-) by OH(-). Magnetic studies
      indicate ferromagnetic interaction between Ni(1) and Ni(2) and possible
      antiferromagnetic between Ni(2) and Ni(2), resulting in a noncollinear system
      which only reaches half of the moment in 50 kOe at 2 K.

PMID- 21714492
TI  - Reductive approach to mixed valency (n = 1-) in the pyrazine ligand-bridged
      [(acac)2Ru(MU-L(2-))Ru(acac)2](n) (L(2-) = 2,5-pyrazine-dicarboxylate) through
      experiment and theory.
AB  - The diruthenium(III) complex [(acac)(2)Ru(MU-L(2-))Ru(acac)(2)] (1) with acac(-)
      = acetylacetonato = 2,4-pentanedionato and a 2,5-pyrazine-dicarboxylato bridge,
      L(2-), has been obtained and structurally characterized as the rac
      (DeltaDelta,LambdaLambda) diastereomer. The Ru(III)Ru(III) configuration in 1
      (d(Ru-Ru) = 6.799 A) results in a triplet ground state (MU = 2.82 MU(B) at 300 K)
      with a density functional theory (DFT) calculated triplet-singlet gap of 10840
      cm(-1) and the metal ions as the primary spin-bearing centers (Mulliken spin
      densities: Ru, 1.711; L, 0.105; acac, 0.184). The paramagnetic 1 exhibits broad,
      upfield shifted (1)H NMR signals with delta values ranging from -10 to -65 ppm
      and an anisotropic electron paramagnetic resonance (EPR) spectrum (<linear
      span>g<linear span> = 2.133, g(1) - g(3) = Deltag = 0.512), accompanied by a weak
      half-field signal at g = 4.420 in glassy frozen acetonitrile at 4 K. Compound 1
      displays two closely spaced oxidation steps to yield labile cations. In contrast,
      two well separated reversible reduction steps of 1 signify appreciable
      electrochemical metal-metal interaction in the Ru(II)Ru(III) mixed-valent state
      1(-) (K(c) ~ 10(7)). The intermediate 1(-) shows a weak, broad Ru(II)->Ru(III)
      intervalence charge transfer (IVCT) band at about 1040 nm (epsilon = 380 M(-1)
      cm(-1)); the DFT approach for 1(-) yielded Mulliken spin densities of 0.460 and
      0.685 for the two metal centers. The monitoring of the nu(C?O) frequencies of the
      uncoordinated C?O groups of L(2-) in 1(n) by IR spectroelectrochemistry suggests
      valence averaging (Ru(2.5)Ru(2.5)) in 1(-) on the vibrational time scale. The
      mixed-valent 1(-) displays a rhombic EPR signal (<linear span>g<linear span> =
      2.239 and Deltag = 0.32) which reveals non-negligible contributions from the
      bridging ligand, reflecting a partial hole-transfer mechanism and being confirmed
      by the DFT-calculated spin distribution (Mulliken spin density of -0.241 for L in
      1(-)). The major low energy electronic transitions in 1(n) (n = 0,-,2-) have been
      assigned as charge transfer processes with the support of TD-DFT analysis.

PMID- 21714493
TI  - Structure-dependent coherent acoustic vibrations of hollow gold nanospheres.
AB  - Hollow gold nanospheres (HGNs) were excited with ultrashort laser pulses, and the
      coherent vibrational response was examined using femtosecond time-resolved
      transient absorption. The results indicated that HGNs support an isotropic mode,
      resulting in periodic modulation of the surface plasmon differential absorption.
      Two different categories of coherent acoustic vibrations, which depend on
      particle dimensions, were observed for HGNs. Further, the vibration launching
      mechanism was dependent upon the dimensions of the HGN. Coherent vibrations in
      HGNs characterized by small outer radii (<10 nm) and low cavity-radius-to-outer
      shell radius aspect ratios (<0.5) were excited by a direct mechanism, whereas the
      vibrations observed for the larger particles (>25 nm OR) with higher aspect
      ratios (>0.5) resulted from an indirect mechanism. These findings may be
      significant for developing a predictive understanding of nanostructure optical
      and mechanical properties.

PMID- 21714494
TI  - Multiscale structural characterizations of fatty acid multilayered tubes with a
      temperature-tunable diameter.
AB  - It is known that 12-hydroxystearic acid coupled via ion-pairing with a
      counterion, such as ethanolamine, self-assembles into supramolecular multilayer
      tubes that exhibit a peculiar temperature-tunable diameter variation. At a given
      temperature threshold (T(O?)), there is a large increase of the tube diameter by
      almost a factor of 10. We investigate here the nature of the counterion on the
      self-assembly of such tubes and the variation of their diameter with the
      temperature. Eight different counterions are used to produce tubes via ion
      pairing with 12-hydroxystearic acid. We systematically measure structural
      parameters at different scales coupling phase contrast microscopy and small-angle
      neutron scattering (SANS), in combination with thermodynamic studies using
      differential scanning calorimetry (DSC). The temperature T(O?) is found to depend
      sensitively on the nature of the counterion. One could not identify any DSC peak
      associated with the diameter variation. However, a detailed line-shape analysis
      of the SANS spectra reveals that a significant softening of the elastic
      properties of the multilayer tube walls occurs at T(O?), for all counterions
      investigated. Depending on both the temperature and the nature of the counterion,
      the interlayer spacing in the multilayered structure (respectively, the bilayer
      thickness) varies in a range from 240 to 440 A (respectively, from 22 to 42 A),
      but those variations appear not to be related to T(O?). Altogether, our results
      show that the variation of the diameter is correlated to the nature of the
      counterion and to the elastic properties of the bilayer stack.

PMID- 21714495
TI  - Metal nanoparticle plasmon-enhanced light-harvesting in a photosystem I thin
      film.
AB  - Silver metal nanoparticle (NP) enhanced fluorescence is investigated in thin
      films of cyanobacterial Photosystem I trimer complexes (PSI) by correlating
      confocal laser scanning microscopy, dark-field imaging, and fluorescence lifetime
      measurements. PSI represents an interesting light-harvesting complex with a 20 nm
      diameter that is not uniformly contained within the surface-localized plasmon
      field of the NPs. With weak far-field illumination, 5- to 20-fold fluorescence
      enhancement is observed for PSI complexes adjacent to NPs, arising from efficient
      nanoparticle light collection and subsequent localized, surface plasmon
      excitation of PSI. Enhanced PSI fluorescence is detected most prominently near
      "rafts" of aggregated NPs that more completely fill the confocal field of view.
      These results demonstrate opportunities to probe energy transfer within
      photosynthetic complexes using plasmonic excitation and to design nanostructures
      for optimizing artificial light-harvesting systems.

PMID- 21714496
TI  - Plasmonic properties of the multispot copper-capped nanoparticle array chip and
      its application to optical biosensors for pathogen detection of multiplex DNAs.
AB  - A localized surface plasmon resonance (LSPR)-based optical biosensor in
      connection with a multispot copper-capped nanoparticle array (MC-NPA) chip was
      proposed and developed. The copper (Cu) films, used as a shell, formed a "cap
      like" layer on the top of the silica nanoparticles, used as a core, in an orderly
      fashion, to form the surface called a "Cu-capped nanoparticle array chip". The
      plasmonic properties of this nanostructure type were initially investigated while
      controlling the shell thickness of the deposited Cu. Also, we quantified the
      sensitivity of MC-NPA chip to changes in bulk refractive index (RI). As a result
      of its LSPR properties, the MC-NPA chip displayed a sensitivity of 67.8 nm per RI
      unit, and the wavelength shift of the LSPR spectrum peak was sensitive to the RI
      of the surrounding bulk medium, such as the biomolecular layers. Using MC-NPA
      chips, multiplex sensing of target DNAs from reference bacteria and clinical
      samples was possible in a quantitative manner with a detection limit of 10 fM (50
      zmol). The optical biosensor developed in this study represents a unique approach
      to performing LSPR that utilizes a simple and cost-effective optical setup with
      disposable chips.

PMID- 21714497
TI  - Mechanics of nanoindentation on a monolayer of colloidal hollow nanoparticles.
AB  - We explore the collective mechanical behavior of monolayer assemblies composed of
      close-packed arrays of hollow silica nanoparticles using a spherical
      nanoindentor. Seven types of well-defined hollow nanoparticles are studied with
      their radii ranging from 100 to 300 nm and shell thickness ranging from 14 to 44
      nm. Micromechanical models reveal the underlying deformation mechanisms during
      indentation, where the consecutive contacting of the indentor with an increasing
      number of nanoparticles results in a nonlinear increase in the indentation force
      with penetration depth. Each contacted hollow nanoparticle successively locally
      bends, flattens, and then locally buckles. The effective indentation modulus of
      the monolayer film, which is obtained by a Hertzian fit to the experimental data,
      is found to be proportional to the elastic modulus of the nanoparticle shell
      material and scales exponentially with the ratio of particle shell thickness t to
      radius R to the power of 2.3. Furthermore, we find that for a constant film
      density with the same (t)/(R) of the constituent nanoparticles, smaller particles
      with a thinner shell can provide a higher effective indentation modulus, compared
      to their larger diameter and thicker shell counterparts. This study provides
      useful insights and guidance for constructing high-performance lightweight
      nanoparticle films and coatings with potential applications in tailoring
      stiffness and mechanical energy absorption.

PMID- 21714499
TI  - Photoconversion mechanism of a green/red photosensory cyanobacteriochrome AnPixJ:
      time-resolved optical spectroscopy and FTIR analysis of the AnPixJ-GAF2 domain.
AB  - The photoconversion mechanism of a green/red sensory cyanobacteriochrome AnPixJ
      was studied. The phycocyanobilin-binding second GAF domain of AnPixJ of Anabaena
      sp. PCC 7120 was expressed in Escherichia coli cells. The His-tagged AnPixJ-GAF2
      domain exhibited photoconversion between the green- and red-absorbing forms,
      APg(543) and APr(648), respectively. We detected four intermediate states in the
      photocycle between them, as follows: APr(648) -> red light -> APr(648)* -> (with
      a rise time constant tau(r) of <100 ns) R1(650-80) (with a decay time constant
      tau(d) of <1 MUs) -> R2(610) (tau(d) = 920 MUs) -> APg(543) -> green light ->
      APg(543)* -> (tau(r) < 50 ns) G1(570) (tau(d) = 190 MUs) -> G2(630) (tau(d) =
      1.01 ms) -> APr(648). These intermediates were named for their absorption peak
      wavelengths, which were estimated on the basis of the time-resolved difference
      spectra and global analysis of the time courses. The absorption spectrum of
      APr(648) resembles that of the Pr form of the phytochrome, while all the other
      states showed peaks at 530-650 nm and had wider bandwidths with smaller peak
      amplitudes. The fastest decay phases of fluorescence from APr(648)* and APg(543)*
      gave lifetimes of 200 and 42 ps, respectively, suggesting fast primary reactions.
      The APg(543)-minus-APr(648) difference FTIR spectrum in an H(2)O medium was
      significantly different from those reported for the Pfr/Pr difference spectra in
      phytochromes. Most of the peaks in the difference spectrum were shifted in the
      D(2)O medium, suggesting the high accessibility to the aqueous phase. The
      interactions of the phycocyanobilin chromophore with the surrounding amino acid
      residues, which are fairly different from those in the GAF domain of
      phytochromes, realize the unique green/red photocycle of AnPixJ.

PMID- 21714498
TI  - Molecular basis for an ancient partnership between prolyl isomerase Pin1 and
      phosphatase inhibitor-2.
AB  - Pin1 is a prolyl isomerase that recognizes phosphorylated Ser/Thr-Pro sites, and
      phosphatase inhibitor-2 (I-2) is phosphorylated during mitosis at a PSpTP site
      that is expected to be a Pin1 substrate. However, we previously discovered I-2,
      but not phospho-I-2, bound to Pin1 as an allosteric modifier of Pin1 substrate
      specificity [Li, M., et al. (2008) Biochemistry 47, 292]. Here, we use binding
      assays and NMR spectroscopy to map the interactions on Pin1 and I-2 to elucidate
      the organization of this complex. Despite having sequences that are ~50%
      identical, human, Xenopus, and Drosophila I-2 proteins all exhibited identical,
      saturable binding to GST-Pin1 with K(0.5) values of 0.3 MUM. The (1)H-(15)N
      heteronuclear single-quantum coherence spectra for both the WW domain and
      isomerase domain of Pin1 showed distinctive shifts upon addition of I-2.
      Conversely, as shown by NMR spectroscopy, specific regions of I-2 were affected
      by addition of Pin1. A single-residue I68A substitution in I-2 weakened binding
      to Pin1 by half and essentially eliminated binding to the isolated WW domain. On
      the other hand, truncation of I-2 to residue 152 had a minimal effect on binding
      to the WW domain but eliminated binding to the isomerase domain. Size exclusion
      chromatography revealed that wild-type I-2 and Pin1 formed a large (>300 kDa)
      complex and I-2(I68A) formed a complex of half the size that we propose are a
      heterotetramer and a heterodimer, respectively. Pin1 and I-2 are conserved among
      eukaryotes from yeast to humans, and we propose they make up an ancient
      partnership that provides a means for regulating Pin1 specificity and function.

PMID- 21714500
TI  - Binding of calcium, magnesium, and target peptides to Cdc31, the centrin of yeast
      Saccharomyces cerevisiae.
AB  - Cdc31, the Saccharomyces cerevisiae centrin, is an EF-hand calcium-binding
      protein essential for the cell division and mRNA nuclear export. We used
      biophysical techniques to investigate its calcium, magnesium, and protein target
      binding properties as well as their conformations in solution. We show here that
      Cdc31 displays one Ca(2+)/Mg(2+) mixed site in the N-terminal domain and two low
      affinity Ca(2+) sites in the C-terminal domain. The affinity of Cdc31 for
      different natural target peptides (from Kar1, Sfi1, Sac3) that we obtained by
      isothermal titration calorimetry shows weakly Ca(2+), but also Mg(2+) dependence.
      The characteristics of target surface binding were shown to be similar; we
      highlight that the 1-4 hydrophobic amino acid motif, in a stable amphipathic
      alpha-helix, is critical for binding. Ca(2+) and Mg(2+) binding increase the
      alpha-helix content and stabilize the structure. Analysis of small-angle X-ray
      scattering experiments revealed that N- and C-terminal domains are not
      individualized in apo-Cdc31; in contrast, they are separated in the Mg(2+) state,
      creating a groove in the middle of the molecule that is occupied by the target
      peptide in the liganded form. Consequently, Mg(2+) seems to have consequences on
      Cdc31's function and could be important to stimulate interactions in resting
      cells.

PMID- 21714501
TI  - Stability and structural evolution of Ce(IV)(1-x)Ln(III)(x)O(2-x/2) solid
      solutions: a coupled MU-Raman/XRD approach.
AB  - Several CeO(2)-based mixed oxides with general composition Ce(1-x)Ln(x)O(2-x/2)
      (for 0 <= x <= 1 and Ln = La, Nd, Sm, Eu, Gd, Dy, Er, or Yb) were prepared using
      an initial oxalic precipitation leading to a homogeneous distribution of cations
      in the oxides. After characterization of the Ce/Nd oxalate precursors and then
      thermal conversion to oxides at T = 1000  degrees C, investigation of the
      crystalline structure of these oxides was carried out by XRD and MU-Raman
      spectroscopy. Typical fluorite Fm 3m structure was obtained for relatively low
      Ln(III) contents, while a cubic Ia 3 superstructure was evidenced above x ~ 0.4.
      Moreover, since Nd(2)O(3) does not crystallize with the Ia 3-type structure, two
      phase systems composed with additional hexagonal Nd(2)O(3) were obtained for
      x(Nd) >= 0.73 in the Ce(1-x)Nd(x)O(2-x/2) series. The effect of heat treatment
      temperature on these limits was explored through MU-Raman spectroscopy, which
      allowed determining the presence of small amounts of the different crystal
      structures observed. In addition, the variation of the Ce(1-x)Ln(x)O(2-x/2) unit
      cell parameter was found to follow a quadratic relation as a result of the
      combination between increasing cationic radius, modifications of cation
      coordination, and decreasing O-O repulsion caused by oxygen vacancies.

PMID- 21714502
TI  - Hydrogen atom abstraction reactions from tertiary amines by benzyloxyl and
      cumyloxyl radicals: influence of structure on the rate-determining formation of a
      hydrogen-bonded prereaction complex.
AB  - A time-resolved kinetic study on the hydrogen atom abstraction reactions from a
      series of tertiary amines by the cumyloxyl (CumO(*)) and benzyloxyl (BnO(*))
      radicals was carried out. With the sterically hindered triisobutylamine,
      comparable hydrogen atom abstraction rate constants (k(H)) were measured for the
      two radicals (k(H)(BnO(*))/k(H)(CumO(*)) = 2.8), and the reactions were described
      as direct hydrogen atom abstractions. With the other amines, increases in
      k(H)(BnO(*))/k(H)(CumO(*)) ratios of 13 to 2027 times were observed. k(H)
      approaches the diffusion limit in the reactions between BnO(*) and unhindered
      cyclic and bicyiclic amines, whereas a decrease in reactivity is observed with
      acyclic amines and with the hindered cyclic amine 1,2,2,6,6
      pentamethylpiperidine. These results provide additional support to our hypothesis
      that the reaction proceeds through the rate-determining formation of a C-H/N
      hydrogen-bonded prereaction complex between the benzyloxyl alpha-C-H and the
      nitrogen lone pair wherein hydrogen atom abstraction occurs, and demonstrate the
      important role of amine structure on the overall reaction mechanism. Additional
      mechanistic information in support of this picture is obtained from the study of
      the reactions of the amines with a deuterated benzyloxyl radical (PhCD(2)O(*),
      BnO(*)-d(2)) and the 3,5-di-tert-butylbenzyloxyl radical.

PMID- 21714503
TI  - Self-assembled TiO2 with increased photoelectron production, and improved
      conduction and transfer: enhancing photovoltaic performance of dye-sensitized
      solar cells.
AB  - Highly crystalline mesoporous anatase TiO(2) is prepared through supramolecular
      self-assembly and by utilizing cetyltrimethylammonium bromide (CTAB) as
      templating material. Photoanodes of dye-sensitized solar cells (DSSCs) made from
      these TiO(2) nanoparticles are found to have a high specific surface area of 153
      m(2)/g and high surface roughness. Optical absorption spectroscopy studies reveal
      that the photoanode films adsorb four times more dye than films made of
      commercial P25 TiO(2). Mercury porosimetry and field emission scanning electron
      microscope (FESEM) studies show hierarchical macro- and meso-porosity of the
      photoanode films leading to better dye and electrolyte percolation, combined with
      improved electron conduction pathways compared to P25 films. Electrochemical
      impedance studies confirm lower impedance and higher electron lifetime in the
      synthesized mesoporous TiO(2) films compared to P25 films. Higher photovoltaic
      efficiency was recorded of cells made from the synthesized mesoporous TiO(2) in
      comparison to the corresponding cells made from P25. Incident-photon-to-current
      efficiency data provided critical understanding of recombination kinetics, and
      provided proof of Mie scattering by the self-assembled submicrometer sized TiO(2)
      aggregates and the macropores in their structure. The scattering phenomenon was
      further corroborated by diffused reflectance studies. An in-depth analysis of
      CTAB-templated mesoporous TiO(2) has been conducted to show how it can be a good
      candidate photoanode material for enhancing the performance of DSSCs.

PMID- 21714504
TI  - LiNi1/3Co1/3Mn1/3O2-graphene composite as a promising cathode for lithium-ion
      batteries.
AB  - The use of graphene as a conductive additive to enhance the discharge capacity
      and rate capability of LiNi(1/3)Co(1/3)Mn(1/3)O(2) electrode material has been
      demonstrated. LiNi(1/3)Co(1/3)Mn(1/3)O(2) and its composite with graphene (90:10
      wt %) were prepared by microemulsion and ball-milling techniques, respectively.
      The structural and morphological features of the prepared materials were
      investigated with powder X-ray diffraction, scanning electron microscopy,
      transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron
      spectroscopy. Characterization techniques depict single-phase
      LiNi(1/3)Co(1/3)Mn(1/3)O(2) with particle sizes in the range of 220-280 nm.
      Electrochemical studies on LiNi(1/3)Co(1/3)Mn(1/3)O(2) and
      LiNi(1/3)Co(1/3)Mn(1/3)O(2)-graphene were conducted using cyclic voltammetry,
      galvanostatic charge-discharge, and electrochemical impedance spectroscopy
      methods by constructing a lithium half-cell. Cyclic voltammograms show the well
      defined redox peaks corresponding to Ni(2+)/Ni(4+). Charge-discharge tests were
      performed at different C rates: 0.05, 1, and 5 between 2.5 and 4.4 V. The results
      indicate the better electrochemical performance of the
      LiNi(1/3)Co(1/3)Mn(1/3)O(2)-graphene composite in terms of high discharge
      capacity (188 mAh/g), good rate capability, and good cycling performance compared
      to LiNi(1/3)Mn(1/3)Co(1/3)O(2). The improved electrochemical performance of the
      LiNi(1/3)Co(1/3)Mn(1/3)O(2)-graphene composite is attributed to a decrease in the
      charge-transfer resistance.

PMID- 21714505
TI  - Electronic coupling between two cyclometalated ruthenium centers bridged by
      1,3,6,8-tetrakis(1-butyl-1H-1,2,3-triazol-4-yl)pyrene.
AB  - A new bridging ligand 1,3,6,8-tetrakis(1-butyl-1H-1,2,3-triazol-4-yl)pyrene
      (ttapyr) was designed and synthesized by "click" chemistry. This ligand was used
      to construct a linear dimetallic biscyclometalated Ru(II) complex
      [(tpy)Ru(ttapyr)Ru(tpy)](2+) and a monometallic complex [(tpy)Ru(ttapyr)](+),
      where tpy is 2,2':6',2"-terpyridine. The electronic properties of these complexes
      were studied and compared by electrochemical and spectroscopic methods with the
      aid of DFT calculations. One-electron oxidation of [(tpy)Ru(ttapyr)Ru(tpy)](2+)
      with cerium ammonium nitrate produced a mixed-valent complex
      [(tpy)Ru(ttapyr)Ru(tpy)](3+). The intramolecular electronic coupling between
      individual metal centers was quantified by the intervalence charge transfer
      transition analysis. Mixed-valent complex [(tpy)Ru(ttapyr)Ru(tpy)](3+) exhibits a
      metal-centered rhombic EPR signal at 77 K with an average g factor of 2.203.

PMID- 21714506
TI  - 1H NMR chemical shift calculations as a probe of supramolecular host-guest
      geometry.
AB  - The self-assembled supramolecular host [Ga(4)L(6)](12-) (1; L = 1,5-bis[2,3
      dihydroxybenzamido]naphthalene) can encapsulate cationic guest molecules within
      its hydrophobic cavity and catalyze the chemical transformations of bound guests.
      The cavity of host 1 is lined with aromatic naphthalene groups, which create a
      magnetically shielded interior environment, resulting in upfield shifted (1-3
      ppm) NMR resonances for encapsulated guest molecules. Using gauge independent
      atomic orbital (GIAO) DFT computations, we show that (1)H NMR chemical shifts for
      guests encapsulated in 1 can be efficiently and accurately calculated and that
      valuable structural information is obtained by comparing calculated and
      experimental chemical shifts. The (1)H NMR chemical shift calculations are used
      to map the magnetic environment of the interior of 1, discriminate between
      different host-guest geometries, and explain the unexpected downfield chemical
      shift observed for a particular guest molecule interacting with host 1.

PMID- 21714507
TI  - Controlling the directional emission of light by periodic arrays of
      heterostructured semiconductor nanowires.
AB  - We demonstrate experimentally the directional emission of light by InAsP segments
      embedded in InP nanowires. The nanowires are arranged in a periodic array,
      forming a 2D photonic crystal slab. The directionality of the emission is
      interpreted in terms of the preferential decay of the photoexcited nanowires and
      the InAsP segments into Bloch modes of the periodic structure. By simulating the
      emission of arrays of nanowires with the emitting segments located at different
      heights, we conclude that the position of this active region strongly influences
      the directionality and efficiency of the emission. Our results will help to
      improve the design of nanowire based LEDs and single photon sources.

PMID- 21714508
TI  - Validation of the distal effect of electron-withdrawing groups on the stability
      of peptide enolates and its exploitation in the controlled stereochemical
      inversion of amino acid derivatives.
AB  - Theoretical studies had predicted that N-electron-withdrawing substituents,
      hydrogen bonding, and protonation at amide nitrogen selectively increase the
      acidity of a distal proton adjacent to the amide carbonyl to the extent that the
      alpha-carbonyl acidity of some N-substituted amides exceeds that of typical
      ketones. Now, in the present work, competitive, base-catalyzed hydrogen-deuterium
      exchange experiments, with diisopropyl ketone and a series of N-substituted
      acetamides and diketopiperazines, have established that there is a strong
      correlation between the calculated acidities and the experimental rates of
      deprotonation in these systems. The results show that the rates of exchange of
      the distal protons of N-acylated and N-sulfonylated amides are more than 4 orders
      of magnitude faster than those of the N-methylated analogues and that the
      acylated and sulfonylated amides are much more reactive in this regard than
      diisopropyl ketone. The magnitude and regioselectivity of the distal effect is
      sufficient for practical applications and has been exploited in the manipulation
      of N-acetyl alpha,alpha'-disubstituted diketopiperazines for the controlled alpha
      deuteration and stereochemical inversion of N-methylamino acids, and in the
      production of alpha-deuterated (2R,3S)-N-methylalloisoleucine from the
      nondeuterated (2S,3S)-isoleucine diastereomer.

PMID- 21714509
TI  - Determinants of the heme-CO vibrational modes in the H-NOX family.
AB  - The Heme Nitric oxide/OXygen binding (H-NOX) family of proteins have important
      functions in gaseous ligand signaling in organisms from bacteria to humans,
      including nitric oxide (NO) sensing in mammals, and provide a model system for
      probing ligand selectivity in hemoproteins. A unique vibrational feature that is
      ubiquitous throughout the H-NOX family is the presence of a high C-O stretching
      frequency. To investigate the cause of this spectroscopic characteristic, the Fe
      CO and C-O stretching frequencies were probed in the H-NOX domain from
      Thermoanaerobacter tengcongensis (Tt H-NOX) using resonance Raman (RR)
      spectroscopy. Four classes of heme pocket mutants were generated to assess the
      changes in stretching frequency: (i) the distal H-bonding network, (ii) the
      proximal histidine ligand, (iii) modulation of the heme conformation via Ile-5
      and Pro-115, and (iv) the conserved Tyr-Ser-Arg (YxSxR) motif. These mutations
      revealed important electrostatic interactions that dampen the back-donation of
      the Fe(II) d(pi) electrons into the CO pi* orbitals. The most significant change
      occurred upon disruption of the H-bonds between the strictly conserved YxSxR
      motif and the heme propionate groups, producing two dominant CO-bound heme
      conformations. One conformer was structurally similar to Tt H-NOX WT, whereas the
      other displayed a decrease in nu(C-O) of up to ~70 cm(-1) relative to the WT
      protein, with minimal changes in nu(Fe-CO). Taken together, these results show
      that the electrostatic interactions in the Tt H-NOX binding pocket are primarily
      responsible for the high nu(C-O) by decreasing the Fe d(pi) -> CO pi* back
      donation and suggest that the dominant mechanism by which this family modulates
      the Fe(II)-CO bond likely involves the YxSxR motif.

PMID- 21714510
TI  - Probing the steric space at the floor of the D1 dopamine receptor orthosteric
      binding domain: 7alpha-, 7beta-, 8alpha-, and 8beta-methyl substituted
      dihydrexidine analogues.
AB  - To probe the space at the floor of the orthosteric ligand binding site in the
      dopamine D(1) receptor, four methylated analogues of dihydrexidine (DHX) were
      synthesized with substitutions at the 7 and 8 positions. The 8alpha-axial, 8beta
      equatorial, and 7alpha-equatorial were synthesized by photochemical cyclization
      of appropriately substituted N-benzoyl enamines, and the 7beta-axial analogue was
      prepared by an intramolecular Henry reaction. All of the methylated analogues
      displayed losses in affinity when compared to DHX (20 nM): 8beta-Me(ax)-DHX (270
      nM), 8alpha-Me(eq)-DHX (920 nM), 7beta-Me(eq)-DHX (6540 nM), and 7alpha-Me(ax)
      DHX (>10000 nM). Molecular modeling studies suggest that although the disruption
      of an aromatic interaction between Phe203(5.47) and Phe288(6.51) is the cause for
      the 14-fold loss in affinity associated with 8beta-axial substitution,
      unfavorable steric interactions with Ser107(3.36) result in the more dramatic
      decreases in binding affinity suffered by the rest of the analogues.

PMID- 21714511
TI  - Superhydrophobic functionalized graphene aerogels.
AB  - Carbon-based nanomaterials such as carbon nanotubes and graphene are excellent
      candidates for superhydrophobic surfaces because of their intrinsically high
      surface area and nonpolar carbon structure. This paper demonstrates that graphene
      aerogels with a silane surface modification can provide superhydrophobicity.
      Graphene aerogels of various concentrations were synthesized and the receding
      contact angle of a water droplet was measured. It is shown that graphene aerogels
      are hydrophobic and become superhydrophobic following the application of a
      fluorinated surfactant. The aerogels produced for this experiment outperform
      previous carbon nanomaterials in creating superhydrophobic surfaces and offer a
      more scalable synthetic procedure for production.

PMID- 21714512
TI  - Resistively detected nuclear magnetic resonance in n- and p-type GaAs quantum
      point contacts.
AB  - We present resistively detected NMR measurements in induced and modulation-doped
      electron quantum point contacts, as well as induced hole quantum point contacts.
      While the magnitude of the resistance change and associated NMR peaks in n-type
      devices is in line with other recent measurements using this technique, the
      effect in p-type devices is too small to measure. This suggests that the
      hyperfine coupling between holes and nuclei in this type of device is much
      smaller than the electron hyperfine coupling, which could have implications in
      quantum information processing.

PMID- 21714513
TI  - Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to alpha,beta
      unsaturated ketones with DIFLUORPHOS and SYNPHOS analogues.
AB  - Applications of electron-deficient DIFLUORPHOS and SYNPHOS analogues in the
      rhodium-catalyzed asymmetric conjugate addition of boronic acids to alpha,beta
      unsaturated ketones afford the 1,4-addition adducts in yields up to 92% and with
      99% ee. Particularly, a Rh-catalyzed asymmetric 1,4-addition of arylboronic acids
      to nonsubstituted maleimide substrates using the (R)-3,5-diCF(3)-SYNPHOS ligand
      is also reported. This protocol provides access to various enantioenriched 3
      substituted succinimide units of biological interest, in high yields and good to
      excellent ee up to 93%, which could be upgraded up to 99% ee, after a single
      crystallization.

PMID- 21714514
TI  - The first nucleotide binding domain of the sulfonylurea receptor 2A contains
      regulatory elements and is folded and functions as an independent module.
AB  - The sulfonylurea receptor 2A (SUR2A) is an ATP-binding cassette (ABC) protein
      that forms the regulatory subunit of ATP-sensitive potassium (K(ATP)) channels in
      the heart. ATP binding and hydrolysis at the SUR2A nucleotide binding domains
      (NBDs) control gating of K(ATP) channels, and mutations in the NBDs that affect
      ATP hydrolysis and cellular trafficking cause cardiovascular disorders. To date,
      there is limited information on the SUR2A NBDs and the effects of disease-causing
      mutations on their structure and interactions. Structural and biophysical studies
      of NBDs, especially from eukaryotic ABC proteins like SUR2A, have been hindered
      by low solubility of the isolated domains. We hypothesized that the solubility of
      heterologously expressed SUR2A NBDs depends on the precise definition of the
      domain boundaries. Putative boundaries of SUR2A NBD1 were identified by structure
      based sequence alignments and subsequently tested by exploring the solubility of
      SUR2A NBD1 constructs with different N and C termini. We have determined
      boundaries of SUR2A NBD1 that allow for soluble heterologous expression of the
      protein, producing a folded domain with ATP binding activity. Surprisingly, our
      alignment and screening data indicate that SUR2A NBD1 contains two putative,
      previously unidentified, regulatory elements: a large insert within the beta
      sheet subdomain and a C-terminal extension. Our approach, which combines the use
      of structure-based sequence alignments and predictions of disordered regions
      combined with biochemical and biophysical studies, may be applied as a general
      method for developing suitable constructs of other NBDs of ABC proteins.

PMID- 21714515
TI  - Structural effects on the electronic properties of extended fused-ring thieno[3,4
      b]pyrazine analogues.
AB  - The synthesis and characterization of the extended thieno[3,4-b]pyrazine
      analogues acenaphtho[1,2-b]thieno[3,4-e]pyrazine (3a), 3,4-dibromoacenaphtho[1,2
      b]thieno[3,4-e]pyrazine (3b), 3-octylacenaphtho[1,2-b]thieno[3,4-e]pyrazine (3c),
      dibenzo[f,h]thieno[3,4-b]quinoxaline (4), and thieno[3',4':5,6]pyrazino[2,3
      f][1,10]phenanthroline (5) are reported. Comparison of structural,
      electrochemical, and photophysical properties to those of simple thieno[3,4
      b]pyrazines are provided in order to provide structure-function relationships
      within this series of compounds.

PMID- 21714516
TI  - Analysis of poly(amidoamine) dendrimer structure by UV-vis spectroscopy.
AB  - We report a UV-vis spectroscopic study of four different types of
      poly(amidoamine) dendrimers. The results indicate that the degree of protonation
      of the interior tertiary amines of these dendrimers correlates directly to an
      absorption band with lambda(max) in the range of 280-285 nm. Specifically, at low
      pH, the tertiary amines are protonated and the 280-285 nm band is absent.
      However, at elevated pH, when these groups are deprotonated, this band appears.
      Similar results were obtained for a simple model compound. The dependence of the
      280-285 nm band on the chemical state of the tertiary amines of the dendrimers
      was confirmed by complexing them with Pd(2+) and Pt(2+). In this case the band
      disappears, and it only reappears when the metal ions are decomplexed following
      reduction with BH(4)(-). Finally, filtration experiments showed that the
      absorption band between 280-285 nm arises exclusively from intact, or nearly
      intact, dendrimers rather than low-molecular-weight fragments.

PMID- 21714517
TI  - Ethanol-assisted graphene oxide-based thin film formation at pentane-water
      interface.
AB  - Graphene oxide (GO) can be viewed as an amphiphilic soft material, which form
      thin films at organic solvent-water interfaces. However, organic solvent
      evaporation provides little driving force, which results in slow GO transfer in
      aqueous phase, thus dawdling GO film formation processes for various potential
      applications. We present an ethanol-assisted self-assembly method for the quick
      formation of GO or GO-based composite thin films with tunable composition,
      transmittance, and surface resistivity at pentane-water interface. The thickness
      of pure GO and reduced GO (rGO) films ranging from ~1 nm to more than 10 nm can
      be controlled by the concentration of GO in bulk solution. The transmittance of
      rGO films can be tuned from 72% to 97% at 550 nm while the surface resistivity
      changes from 8.3 to 464.6 kOmega sq(-1). Ethanol is essential for achieving quick
      formation of GO thin films. When ethanol is injected into GO aqueous dispersion,
      it serves as a nonsolvent, compromising the stability of GO and providing driving
      force to allow GO sheets aggregate at the water-pentane interface. On the other
      hand, neither the evaporation of pentane nor the mixing between ethanol and water
      provides sufficient driving forces to allow noteworthy amount of GO sheets to
      migrate from the bulk aqueous phase to the interface. This method can also be
      extended to prepare GO-based composites thin films with tunable composition, such
      as GO/single walled carbon nanotube (SWCNT) composite thin films investigated in
      this work. Reduced GO/SWCNT composite films show much lower surface resistivity
      compared to pure rGO thin films. This ethanol-assisted self-assembly method opens
      opportunities to design and fabricate new functional GO-based hybrid materials
      for various potential applications.

PMID- 21714518
TI  - Electromechanical actuation and current-induced metastable states in suspended
      single-crystalline VO2 nanoplatelets.
AB  - Current-induced electromechanical actuation enabled by the metal-insulator
      transition in VO(2) nanoplatelets is demonstrated. The Joule heating by a
      sufficient current flowing through suspended nanoplatelets results in formation
      of heterophase domain patterns and is accompanied by nanoplatelet deformation.
      The actuation action can be achieved in a wide temperature range below the bulk
      phase transition temperature (68  degrees C). The observed current-sustained
      heterophase domain structures should be interpreted as distinct metastable states
      in free-standing and end-clamped VO(2) samples. We analyze the main prerequisites
      for the realization of a current-controlled actuator based on the proposed
      concept.

PMID- 21714519
TI  - Four-electron oxygen reduction by tetrathiafulvalene.
AB  - The four-electron reduction of oxygen by tetrathiafulvalene (TTF) in acidified
      1,2-dichloroethane and at the acidified water/1,2-dichloroethane interface has
      been observed. Spectroscopy and ion transfer voltammetry results suggest that the
      reaction proceeds by the fast protonation of TTF followed by the 4-electron
      reduction of oxygen to form water. Electronic structure computations give
      evidence of the formation of a helical tetramer assembly ([TTF(4)H(2)](2+)) of
      two protonated TTF and two neutral TTF molecules. The protonated tetramer is
      potentially able to deliver the four electrons needed for the oxygen reduction.
      The production of water was corroborated by (1)H NMR analysis.

PMID- 21714520
TI  - Simulant molecules with trivalent or pentavalent phosphorus atoms: bond
      dissociation energies and other thermodynamic and structural properties from
      quantum chemical models.
AB  - The CBS-QB3 and G4 thermochemical models have been used to generate energetic,
      structural, and spectroscopic data on a set of molecules with trivalent or
      pentavalent phosphorus atoms that can serve as simulants of chemical warfare
      agents. Based on structural data, the conformational stabilities of these
      molecules are explained in terms of the anomeric interaction within the OPOC and
      OPSC fragments. For those cases where experimental data are available,
      comparisons have been made between calculated and previously reported vibrational
      frequencies. All varieties of bond dissociation energies have been examined
      except those for C-H and P?O bonds. In trivalent phosphorus molecules, the O-C
      and S-C bonds have the lowest dissociation energies. In the pentavalent
      phosphorus set, the S-C bonds, followed by P-S bonds, have the lowest
      dissociation energies. In the fluorinated simulant molecules, the P-F bond is
      strongest, and the P-C or O-C bonds are weakest.

PMID- 21714521
TI  - Analysis of cationic structure in some room-temperature molten fluorides and
      dependence of their ionic conductivity and viscosity on hydrofluoric acid
      concentration.
AB  - To understand the ionic and nonionic species in (CH(3))(4)NF.mHF,
      (CH(3))(3)N.mHF, (C(2)H(5))(4)NF.mHF, and (C(2)H(5))(3)N.mHF melts, the
      structures of these melts were investigated by infrared spectroscopy, NMR, and
      high-energy X-ray diffraction. Infrared spectra revealed that three kinds of
      fluorohydrogenate anions, (FH)(n)F(-) (n = 1, 2, and 3), and molecular
      hydrofluoric acid (HF) are present in every melt. Ionic conductivity and
      viscosity of these melts were measured and correlated with their cationic
      structure. The ionic conductivity of the R(4)N(+)-systems was higher than that of
      corresponding R(3)NH(+)-systems because a strong N-H...F(HF)(n) interaction
      prevents the motion of R(3)NH(+) cations in the R(3)N.mHF melts. (CH(3))(4)N(+)
      and (CH(3))(3)NH(+) cations gave higher ionic conductivity than (C(2)H(5))(4)N(+)
      and (C(2)H(5))(3)NH(+) cations, respectively, because the ionic radii of former
      cations were smaller than those of latter. It was concluded that these effects on
      ionic conductivity can be explained by the cationic structure and the
      concentration of molecular HF in the melts.

PMID- 21714522
TI  - Preliminary finding on a new calcium channel entry blocker chemotype: 5,6-diamino
      4-hydroxy-2-mercaptopyrimidine derivatives.
AB  - We report the preliminary in vitro characterization of a series of pyrimidines as
      a new chemotype that modulates cardiovascular parameters and relaxes ileum smooth
      muscle according to classical calcium entry blockers. Tested compounds showed an
      interesting negative inotropic selectivity. In patch-clamp experiments they block
      L- over T-type calcium currents. Two requisites seem essential for the activity:
      lipophilic substituents in positions 2 and 5 of the pyrimidine ring and the
      acetamidic function in position 6.

PMID- 21714523
TI  - Self-assembled plasmonic core-shell clusters with an isotropic magnetic dipole
      response in the visible range.
AB  - We theoretically analyze, fabricate, and characterize a three-dimensional
      plasmonic nanostructure that exhibits a strong and isotropic magnetic response in
      the visible spectral domain. Using two different bottom-up approaches that rely
      on self-organization and colloidal nanochemistry, we fabricate clusters
      consisting of dielectric core spheres, which are smaller than the wavelength of
      the incident radiation and are decorated by a large number of metallic
      nanospheres. Hence, despite having a complicated inner geometry, such a core
      shell particle is sufficiently small to be perceived as an individual object in
      the far field. The optical properties of such complex plasmonic core-shell
      particles are discussed for two different core diameters.

PMID- 21714524
TI  - Contemporaneous dual catalysis: chemoselective cross-coupling of catalytic
      vanadium-allenoate and pi-allylpalladium intermediates.
AB  - This paper presents a detailed investigation of a dual catalytic system that
      combines a vanadium-catalyzed Meyer-Schuster rearrangement and a palladium
      catalyzed allylic alkylation. The implementation of this novel reaction relies on
      matching the formation rates of vanadium-allenoate and pi-allylpalladium
      intermediates with their bimolecular coupling rate in order to minimize the
      undesired protonation or O-alkylation of the catalytically generated
      intermediates. Chemoselectivity in this dual catalytic process was successfully
      achieved by adjusting ligand structure and catalyst loading ratios of the
      vanadium and palladium catalysts. A great range of coupling partners for both the
      propargyl alcohol and allyl carbonate components are readily accommodated in this
      new transformation, which in turn provides a novel avenue to a variety of alpha
      allylated alpha,beta-unsaturated ketones, esters, and amides in moderate to
      excellent isolated yields.

PMID- 21714525
TI  - X-ray crystallographic, FT-IR, and density functional theory studies of the salt
      formed between dipicrylamine and 1,5,7-triazabicyclo[4.4.0]dec-1-ene.
AB  - The DPA-TBD (dipicrylamine-1,5,7-triazabicyclo[4.4.0]dec-1-ene) salt has been
      synthesized and characterized by FT-IR spectroscopy, X-ray single-crystal
      diffraction, and theoretical study. In the FT-IR spectrum of the crystalline DPA
      TBD salt, an unexpected intense band at 1742 cm(-1) is present. The optimized
      geometry and the FT-IR spectra of the DPA salt were calculated at the B3LYP/6
      31G+(d) level and give an explanation of the nature of this band as the nu(C?N?C)
      vibration. For comparison, the calculated IR spectra of the DPA anion, hydrogen
      bonded DPA anion, and neutral DPA and TBD molecules as well as for the TBD cation
      are also shown. The presence of the free DPA anion in the gas phase was directly
      detected in the negative ion mode electrospray ionization MS spectra. The
      fragmentation of the DPA anion is also discussed.

PMID- 21714526
TI  - Structure-activity relationships of phosphoinositide 3-kinase (PI3K)/mammalian
      target of rapamycin (mTOR) dual inhibitors: investigations of various 6,5
      heterocycles to improve metabolic stability.
AB  - N-(6-(6-Chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2
      yl)acetamide (1) is a potent and efficacious inhibitor of PI3Kalpha and mTOR in
      vitro and in vivo. However, in hepatocyte and in vivo metabolism studies, 1 was
      found to undergo deacetylation on the 2-amino substituent of the benzothiazole.
      As an approach to reduce or eliminate this metabolic deacetylation, a variety of
      6,5-heterocyclic analogues were examined as an alternative to the benzothiazole
      ring. Imidazopyridazine 10 was found to have similar in vitro potency and in vivo
      efficacy relative to 1, while only minimal amounts of the corresponding
      deacetylated metabolite of 10 were observed in hepatocytes.

PMID- 21714527
TI  - First-principles study of lattice dynamics and thermodynamics of TiO2 polymorphs.
AB  - The structural, phonon, and thermodynamic properties of six TiO(2) polymorphs,
      i.e., rutile, anatase, columbite, baddeleyite, orthorhombic I, and cotunnite,
      have been systematically investigated by density functional theory. The predicted
      volumes, bulk modulus, and Debye temperature are in good agreement with
      experiments. The phonon dispersions of the TiO(2) polymorphs were studied by the
      supercell approach, whereas the long-range dipole-dipole interactions were
      calculated by linear response theory to reproduce the LO-TO splitting, making
      accurate prediction of phonon frequencies for the polar material TiO(2). The
      calculated phonon dispersions show that all TiO(2) polymorphs are dynamically
      stable at ambient pressure, indicating the high-pressure phases might be quenched
      to ambient conditions as ultrahard materials. Furthermore, the finite temperature
      thermodynamic properties of TiO(2) polymorphs were predicted accurately from the
      obtained phonon density of states, which is critical in the future study of the
      pressure-temperature phase diagram of TiO(2). The calculated Gibbs energies
      reveal that rutile is more stable than anatase at ambient pressure. We derived
      the Gibbs energy and heat capacity functions for all TiO(2) polymorphs for use in
      thermodynamic modeling of phase equilibria.

PMID- 21714528
TI  - Proton coupled electron transfer and redox-active tyrosine Z in the
      photosynthetic oxygen-evolving complex.
AB  - Proton coupled electron transfer (PCET) reactions play an essential role in many
      enzymatic processes. In PCET, redox-active tyrosines may be involved as
      intermediates when the oxidized phenolic side chain deprotonates. Photosystem II
      (PSII) is an excellent framework for studying PCET reactions, because it contains
      two redox-active tyrosines, YD and YZ, with different roles in catalysis. One of
      the redox-active tyrosines, YZ, is essential for oxygen evolution and is rapidly
      reduced by the manganese-catalytic site. In this report, we investigate the
      mechanism of YZ PCET in oxygen-evolving PSII. To isolate YZ(*) reactions, but
      retain the manganese-calcium cluster, low temperatures were used to block the
      oxidation of the metal cluster, high microwave powers were used to saturate the
      YD(*) EPR signal, and YZ(*) decay kinetics were measured with EPR spectroscopy.
      Analysis of the pH and solvent isotope dependence was performed. The rate of
      YZ(*) decay exhibited a significant solvent isotope effect, and the rate of
      recombination and the solvent isotope effect were pH independent from pH 5.0 to
      7.5. These results are consistent with a rate-limiting, coupled proton electron
      transfer (CPET) reaction and are contrasted to results obtained for YD(*) decay
      kinetics at low pH. This effect may be mediated by an extensive hydrogen-bond
      network around YZ. These experiments imply that PCET reactions distinguish the
      two PSII redox-active tyrosines.

PMID- 21714529
TI  - Quantitative analysis of microRNA in blood serum with protein-facilitated
      affinity capillary electrophoresis.
AB  - MicroRNAs (miRNAs) are small (~22 nt) regulatory RNAs that are frequently
      deregulated in cancer and have shown promise as tissue- and blood-based
      biomarkers for cancer classification and prognostication. Here we present a
      protein-facilitated affinity capillary electrophoresis (ProFACE) assay for rapid
      quantification of miRNA levels in blood serum using single-stranded DNA binding
      protein (SSB) and double-stranded RNA binding protein (p19) as separation
      enhancers. The method utilizes either the selective binding of SSB to a single
      stranded DNA/RNA probe or the binding of p19 to miRNA-RNA probe duplex. For the
      detection of ultralow amounts of miRNA without polymerase chain reaction (PCR)
      amplification in blood samples we apply off-line preconcentration of synthetic
      miRNA-122 from serum by p19-coated magnetic beads followed by online sample
      stacking in the ProFACE assay. The detection limit is 0.5 fM or 30 000 miRNA
      molecules in 1 mL of serum as a potential source of naive miRNAs.

PMID- 21714530
TI  - Synthesis of 7,7'-dihydroxy-8,8'-biquinolyl (azaBINOL) via Pd-catalyzed directed
      double C-H functionalization of 8,8'-biquinolyl: emergence of an atropos from a
      tropos state.
AB  - 7,7'-Dihydroxy-8,8'-biquinolyl (azaBINOL) was prepared from 2-chloroaniline in
      four steps: (1) the Skraup reaction, (2) Ni-catalyzed reductive coupling of 8
      chloroquinoline, (3) Pd(II)-catalyzed double C-H functionalization of 8,8'
      biquinolyl mediated by PhI(OAc)(2), and (4) saponification. During the third
      step, an axially chiral (atropos type) biaryl molecule was directly generated
      from an essentially achiral (tropos type) biaryl starting material.

PMID- 21714531
TI  - Schicagenins A-C: three cagelike nortriterpenoids from leaves and stems of
      Schisandra chinensis.
AB  - Schicagenins A-C (1-3), three unprecedented nortriterpenoids characterized with a
      tetracyclic oxa-cage motif and C(9) side chain, were discovered from the leaves
      and stems of Schisandra chinensis. Their structures were determined on the basis
      of extensive spectroscopic analysis, and the absolute stereochemistries were
      established by single-crystal X-ray diffraction and CD experiments. A plausible
      biosynthetic pathway of 1-3 was also discussed.

PMID- 21714532
TI  - AcquaAlta: a directional approach to the solvation of ligand-protein complexes.
AB  - Water molecules mediating polar interactions in ligand-protein complexes can
      substantially contribute to binding affinity and specificity. To account for such
      water molecules in computer-aided drug design, we performed an extensive search
      in the Cambridge Structural Database (CSD) to identify the geometrical criteria
      defining interactions of water molecules with ligand and protein. In addition,
      with ab initio calculations the propensity of ligand hydration was evaluated.
      Based on this information, we developed an algorithm (AcquaAlta) to reproduce
      water molecules bridging polar interactions between ligand and protein moieties.
      This approach was validated with 20 crystal structures and yielded a match of 76%
      between experimental and calculated water positions. When water molecules
      establishing only weak interactions with the protein were neglected, the match
      could be improved to 88%. Supported by a pharmacophore-based alignment tool, the
      solvation algorithm was then applied to the docking of oligopeptides to the
      periplasmic oligopeptide binding protein A (OppA). Calculated waters based on the
      crystal poses matched an average of 66% of the experimental waters. With water
      molecules calculated based on the docked ligands, the average match with the
      experimental waters dropped to 53%.

PMID- 21714533
TI  - Expedient synthesis of N-acyl anthranilamides and beta-enamine amides by the
      Rh(III)-catalyzed amidation of aryl and vinyl C-H bonds with isocyanates.
AB  - A Rh(III)-catalyzed protocol for the amidation of anilide and enamide C-H bonds
      with isocyanates has been developed. This method provides direct and efficient
      syntheses of N-acyl anthranilamides, enamine amides, and pyrimidin-4-one
      heterocycles.

PMID- 21714534
TI  - New way to analyze the adsorption behavior of flavonoids on macroporous
      adsorption resins functionalized with chloromethyl and amino groups.
AB  - A series of macroporous adsorption resins (MARs) with novel structure were
      synthesized on the basis of the Friedel-Crafts catalyzed and amination reaction.
      Adsorption feature of the synthetic resins with respect to the purification
      effect were investigated systemically by employing rutin as the adsorbate.
      Different from traditional adsorption patterns, the results showed interesting
      conclusions: (1) With the increase in the temperature of the experiment, the
      adsorption capacity increased gradually; with the increase in the concentration
      of the initial solution, the adsorption capacity increased to the maximum and
      then decreased gradually. (2) The classical models that the inductive effect
      transmitted to the first layer and the adsorption process contained in one
      compartment could not explain our experimental results reasonably. Thus, a new
      adsorption isotherm model that the inductive effect passed on to a higher layer
      and a new adsorption kinetics model in which the adsorption process contained
      more compartments were created according to the multiparameter theory and
      Karickhoff's theory by investigating the regression of the experimental results.
      The conclusion that the inductive effect passed to the fourth layer and the
      adsorption process contained four compartments was drawn.

PMID- 21714535
TI  - Suppression of magnetic order in Sr3Fe2O4Cl2 by Fe-site substitution by cobalt.
AB  - The low-temperature topotactic reduction of Sr(3)Fe(2-x)Co(x)O(5)Cl(2)
      oxychloride phases with LiH allows the preparation of phases of composition
      Sr(3)Fe(2-x)Co(x)O(4)Cl(2) (0 <= x <= 1). The reduced phases adopt body-centered
      tetragonal structures which are isostructural with Sr(3)Fe(2)O(4)Cl(2) and
      contain square-planar (Fe/Co)O(4) centers connected into apex-linked sheets,
      analogous to the CuO(2) sheets present in superconducting cuprate phases. As the
      cobalt concentration in Sr(3)Fe(2-x)Co(x)O(4)Cl(2) is increased the
      antiferromagnetic order of the Sr(3)Fe(2)O(4)Cl(2) host phase is suppressed,
      ultimately leading to spin-glass behavior, at low temperature, in Sr(3)Fe(2
      x)Co(x)O(4)Cl(2) phases with x >= 0.8. The limited influence of cobalt
      substitution on the reactions which form the Sr(3)Fe(2-x)Co(x)O(4)Cl(2) phases is
      discussed and contrasted to that of the related SrFeO(3-delta)-SrFeO(2) system.

PMID- 21714536
TI  - Rational design of potent, small, synthetic allosteric inhibitors of thrombin.
AB  - Thrombin is a key enzyme targeted by the majority of current anticoagulants that
      are direct inhibitors. Allosteric inhibition of thrombin may offer a major
      advantage of finely tuned regulation. We present here sulfated benzofurans as the
      first examples of potent, small allosteric inhibitors of thrombin. A sulfated
      benzofuran library of 15 sulfated monomers and 13 sulfated dimers with different
      charged, polar, and hydrophobic substituents was studied in this work. Synthesis
      of the sulfated benzofurans was achieved through a multiple step, highly branched
      strategy, which culminated with microwave-assisted chemical sulfation. Of the 28
      potential inhibitors, 11 exhibited reasonable inhibition of human alpha-thrombin
      at pH 7.4. Structure-activity relationship analysis indicated that sulfation at
      the 5-position of the benzofuran scaffold was essential for targeting thrombin. A
      tert-butyl 5-sulfated benzofuran derivative was found to be the most potent
      thrombin inhibitor with an IC(50) of 7.3 MUM under physiologically relevant
      conditions. Michaelis-Menten studies showed an allosteric inhibition phenomenon.
      Plasma clotting assays indicate that the sulfated benzofurans prolong both the
      activated partial thromboplastin time and prothrombin time. Overall, this work
      puts forward sulfated benzofurans as the first small, synthetic molecules as
      powerful lead compounds for the design of a new class of allosteric inhibitors of
      thrombin.

PMID- 21714537
TI  - Tailored one- and two-dimensional self-assembly of a perylene diimide derivative
      in organic solvents.
AB  - We report on studies of the tailored self-assembly of the perylene diimide
      derivative, N,N'-ditridecylperylene-3,4,9,10-tetracarboxylic diimide, into
      structures with fibrous gel-type, one-dimensional, and two-dimensional
      morphologies. This approach for producing highly ordered nanostructures of well
      defined morphologies utilizes a property of pi-conjugated molecules to assemble
      in poor organic solvents due to pi-pi interaction between the aromatic cores and
      takes advantage of the temperature dependence of solubility. The morphology
      control is based on a fine-tuning of anisotropic, intermolecular solute-solute
      interactions that are attenuated by the solute-solvent interaction in organic
      solvents of different chemical structure. We discuss the role of light
      illumination in the self-assembly process as well as application of ultrasonic
      treatment as a way of mechanical tailoring of morphology. This approach paves the
      way toward the molecular-scale tailoring of structural properties of organic
      semiconducting materials for electronic and optoelectronic applications.

PMID- 21714538
TI  - Discovery of a tetrahydroisoquinoline-based hydroxamic acid derivative (ZYJ-34c)
      as histone deacetylase inhibitor with potent oral antitumor activities.
AB  - Histone deacetylase (HDAC) has emerged as an attractive target for the
      development of antitumor agents during the past decade. Previously
      tetrahydroisoquinoline-bearing hydroxamic acid analogue, ZYJ-25e (1), was
      identified and validated as a potent histone deacetylase inhibitor (HDACi) with
      marked in vitro and in vivo antitumor potency. In the present study, further
      modification of 1 led to another more potent, orally active HDACi, ZYJ-34c (4).
      Compared to FDA-approved drug suberoylanilide hydroxamic acid (SAHA), compound 4
      exhibited higher in vivo antitumor potency in a human breast carcinoma (MDA-MB
      231) xenograft model and in a mouse hepatoma-22 (H22) pulmonary metastasis model
      and similar in vivo antitumor potency in a human colon tumor (HCT116) xenograft
      model.

PMID- 21714539
TI  - Utilization of halogen bond in lead optimization: a case study of rational design
      of potent phosphodiesterase type 5 (PDE5) inhibitors.
AB  - For proof-of-concept of halogen bonding in drug design, a series of halogenated
      compounds were designed based on a lead structure as new inhibitors of
      phosphodiesterase type 5. Bioassay results revealed a good correlation between
      the measured bioactivity and the calculated halogen bond energy. Our X-ray
      crystal structures verified the existence of the predicted halogen bonds,
      demonstrating that the halogen bond is an applicable tool in drug design and
      should be routinely considered in lead optimization.

PMID- 21714540
TI  - Rapid evaluation of the antibacterial activity of arylene-ethynylene compounds.
AB  - A series of oligo(arylene-ethynylene) (1-3 repeat units) compounds functionalized
      with quaternary ammonium groups was screened for their antibacterial activity in
      the dark and with activation by long-wavelength (365 nm) UV irradiation. Several
      of these compounds have effective bactericidal activity (>99.9% killing) at
      concentrations between 0.01 and 10 MUg/mL. Our approach uses flow cytometry to
      rapidly screen and evaluate the susceptibility of bacterial populations. The
      rapidity, high information content, and accuracy of this approach make it an
      extremely valuable method for the study of antibacterial compounds.

PMID- 21714541
TI  - Superswollen microemulsions stabilized by shear and trapped by a temperature
      quench.
AB  - We studied the solubilization of oil in the C(16)E(8)/hexadecane/H(2)O system.
      Close to the phase inversion temperature (PIT), the system, at equilibrium, can
      form either homogeneous states (i.e., microemulsions) at high surfactant
      concentrations or three-phase states at lower concentrations. We show that, under
      gentle shear, at a line we named the clearing boundary (CB), located a few
      degrees below the PIT, the system is homogeneous regardless of the surfactant
      concentration. We relate this shift of the microemulsion boundary to shear
      induced disruption of the asymmetric bicontinuous structure. Although this state
      quickly relaxes to equilibrium when shear is stopped, we show that it is still
      possible to trap it into a metastable state through a temperature quench. This
      method is the sub-PIT emulsification that we described in a previous work (Roger
      Langmuir 2010, 26, 3860-3867).

PMID- 21714542
TI  - Enantioselective, palladium-catalyzed alpha-arylation of N-Boc pyrrolidine: in
      situ react IR spectroscopic monitoring, scope, and synthetic applications.
AB  - A comprehensive study of the enantioselective Pd-catalyzed alpha-arylation of N
      Boc pyrrolidine has been carried out. The protocol involves deprotonation of N
      Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et(2)O at -78  degrees C,
      transmetalation with ZnCl(2) and Negishi coupling using Pd(OAc)(2), t-Bu(3)P
      HBF(4) and the aryl bromide. This paper reports several new features including in
      situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and
      the (+)-sparteine surrogate to access products with opposite configuration;
      development of a catalytic asymmetric lithiation-Negishi coupling reaction;
      extension to a wide range of heteroaromatic bromides; total synthesis of (R)
      crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and
      examples of alpha-vinylation of N-Boc pyrrolidine using vinyl bromides
      exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus
      establishing its configuration as (R)). In this way, the full scope and
      limitations of the methodology are delineated.

PMID- 21714543
TI  - Hazardous air pollutant formation from pyrolysis of typical Chinese casting
      materials.
AB  - Analytical pyrolysis was conducted to evaluate the major hazardous air pollutant
      (HAP) emissions from pyrolysis of bituminous coal and a furan binder, which are
      the two most commonly used casting materials for making green sand and furan no
      bake molds in Chinese foundries. These two materials were flash pyrolyzed in a
      Curie-point pyrolyzer at 920  degrees C and slowly pyrolyzed in a
      thermogravimetric analyzer (TGA) from ambient temperature to 1000  degrees C with
      a heating rate of 30  degrees C/min. The emissions from Curie-point and TGA
      pyrolysis were analyzed with gas chromatography-mass spectrometer/flame
      ionization detector. Thirteen HAP species were identified and quantified in the
      pyrolysis emissions of the two materials. The prominent HAP emissions were
      cresols, benzene, toluene, phenol, and naphthalene for the bituminous coal,
      whereas they were m,p,o-xylenes for the furan binder. Xylenesulfonic acid, the
      acidic catalyst in furan binder, was found to be the major source of xylene
      emissions. Thermogravimetry-mass spectrometer monitored the evolution of HAP
      emissions during TGA pyrolysis. For both of the casting materials, most of the
      emissions were released in the temperature range of 350-700  degrees C.

PMID- 21714544
TI  - Identification of guanylate-binding protein 1 as a potential oral cancer marker
      involved in cell invasion using omics-based analysis.
AB  - Oral cavity squamous cell carcinoma (OSCC) is a devastating disease that accounts
      for 3% of all cancer cases diagnosed annually. OSCC is usually diagnosed at
      advanced clinical stages, resulting in poor outcomes. To identify effective
      biomarkers for improved OSCC diagnosis and/or management, we simultaneously
      analyzed the OSCC cell secretome and tissue transcriptome. Among the 19
      candidates isolated, guanylate-binding protein 1 (GBP1) was selected for further
      validation using serum samples from OSCC patients and healthy controls. Notably,
      the serum level of GBP1 was higher in OSCC patients, compared to that in healthy
      controls. Immunohistochemical analysis further revealed GBP1 overexpression in
      OSCC tissues, compared with adjacent noncancerous epithelia. Importantly, the
      higher GBP1 level in OSCC tissue was associated with higher overall pathological
      stage, positive perineural invasion, and poorer prognosis. Moreover, GBP1
      modulated the migration and invasion of OSCC cells in vitro. Our results
      collectively indicate that integrated analysis of the cancer secretome and
      transcriptome is a feasible strategy for the efficient identification of novel
      OSCC markers.

PMID- 21714545
TI  - Detachment of deposited colloids by advancing and receding air-water interfaces.
AB  - Moving air-water interfaces can detach colloidal particles from stationary
      surfaces. The objective of this study was to quantify the effects of advancing
      and receding air-water interfaces on colloid detachment as a function of
      interface velocity. We deposited fluorescent, negatively charged, carboxylate
      modified polystyrene colloids (diameter of 1 MUm) into a cylindrical glass
      channel. The colloids were hydrophilic with an advancing air-water contact angle
      of 60 degrees  and a receding contact angle of 40 degrees . After colloid
      deposition, two air bubbles were sequentially introduced into the glass channel
      and passed through the channel at different velocities (0.5, 7.7, 72, 982, and
      10,800 cm/h). The passage of the bubbles represented a sequence of receding and
      advancing air-water interfaces. Colloids remaining in the glass channel after
      each interface passage were visualized with confocal microscopy and quantified by
      image analysis. The advancing air-water interface was significantly more
      effective in detaching colloids from the glass surface than the receding
      interface. Most of the colloids were detached during the first passage of the
      advancing air-water interface, while the subsequent interface passages did not
      remove significant amounts of colloids. Forces acting on the colloids calculated
      from theory corroborate our experimental results, and confirm that the detachment
      forces (surface tension forces) during the advancing air-water interface movement
      were stronger than during the receding movement. Theory indicates that, for
      hydrophilic colloids, the advancing interface movement generally exerts a
      stronger detachment force than the receding, except when the hysteresis of the
      colloid-air-water contact angle is small and that of the channel-air-water
      contact angle is large.

PMID- 21714546
TI  - Selective growth of Au nanoparticles on (111) facets of Cu2O microcrystals with
      an enhanced electrocatalytic property.
AB  - The selective growth of Au nanoparticles on (111) facets of truncated octahedral
      and cuboctahedral Cu(2)O crystals has been achieved by exploiting the differences
      in the standard potential between AuCl(4)(-)/Au and Cu(2+)/Cu(2)O pairs and in
      surface energies between (111) and (100) planes. The density and size of Au
      nanoparticles can be controlled by tuning the concentration of the gold
      precursor. Truncated octahedral Cu(2)O-Au nanocomposites have a 10 times higher
      electrochemically catalytic activity toward H(2)O(2) reduction than do pure
      Cu(2)O crystals. The enhanced catalysis may be derived from the polarization of
      Au NPs at the interface, which makes Cu(2)O more active for H(2)O(2) reduction.

PMID- 21714547
TI  - Uptake of Sr2+ and Co2+ into biogenic hydroxyapatite: implications for biomineral
      ion exchange synthesis.
AB  - Biomineral hydroxyapatite (Bio-HAp) produced by Serratia sp. has the potential to
      be a suitable material for the remediation of metal contaminated waters and as a
      radionuclide waste storage material. Varying the Bio-HAp manufacturing method was
      found to influence hydroxyapatite (HAp) properties and consequently the uptake of
      Sr(2+) and Co(2+). All the Bio-HAp tested in this study were more efficient than
      the commercially available hydroxyapatite (Com-HAp) for Sr(2+) and Co(2+) uptake.
      For Bio-HAp the uptake for Sr(2+) and Co(2+) ranged from 24 to 39 and 29 to 78
      mmol per 100 g, respectively. Whereas, the uptake of Sr(2+) and Co(2+) by Com-HAp
      ranged from 3 to 11 and 4 to 18 mmol per 100 g, respectively. Properties that
      increased metal uptake were smaller crystallite size (<40 nm) and higher surface
      area (>70 m(2) g(-1)). Organic content which influences the structure (e.g.,
      crystallite arrangement, size and surface area) and composition of Bio-HAp was
      also found to be important in Sr(2+) and Co(2+) uptake. Overall, Bio-HAp shows
      promise for the remediation of aqueous metal waste especially since Bio-HAp can
      be synthesized for optimal metal uptake properties.

PMID- 21714548
TI  - DNA-directed artificial light-harvesting antenna.
AB  - Designing and constructing multichromophoric, artificial light-harvesting
      antennas with controlled interchromophore distances, orientations, and defined
      donor-acceptor ratios to facilitate efficient unidirectional energy transfer is
      extremely challenging. Here, we demonstrate the assembly of a series of
      structurally well-defined artificial light-harvesting triads based on the
      principles of structural DNA nanotechnology. DNA nanotechnology offers
      addressable scaffolds for the organization of various functional molecules with
      nanometer scale spatial resolution. The triads are organized by a self-assembled
      seven-helix DNA bundle (7HB) into cyclic arrays of three distinct chromophores,
      reminiscent of natural photosynthetic systems. The scaffold accommodates a
      primary donor array (Py), secondary donor array (Cy3) and an acceptor (AF) with
      defined interchromophore distances. Steady-state fluorescence analyses of the
      triads revealed an efficient, stepwise funneling of the excitation energy from
      the primary donor array to the acceptor core through the intermediate donor. The
      efficiency of excitation energy transfer and the light-harvesting ability
      (antenna effect) of the triads was greatly affected by the relative ratio of the
      primary to the intermediate donors, as well as on the interchromophore distance.
      Time-resolved fluorescence analyses by time-correlated single-photon counting
      (TCSPC) and streak camera techniques further confirmed the cascading energy
      transfer processes on the picosecond time scale. Our results clearly show that
      DNA nanoscaffolds are promising templates for the design of artificial photonic
      antennas with structural characteristics that are ideal for the efficient
      harvesting and transport of energy.

PMID- 21714549
TI  - Proteomic characterization of human milk fat globule membrane proteins during a
      12 month lactation period.
AB  - The milk fat globule membrane (MFGM) contains proteins which have been implicated
      in a variety of health benefits. Milk fat globule membrane proteins were isolated
      from human milk during a 12 month lactation period and subjected to in-solution
      digestion and liquid chromatography tandem mass spectrometry analysis. Data were
      pooled, and our results showed that 191 proteins were identified. Relative
      quantification of the identified MFGM proteins during the course of lactation was
      performed by label free spectral counting and differentiation expression
      analysis, which showed some proteins decreasing during the course of lactation
      whereas some increased or remained at a relatively constant level. The human MFGM
      proteins are distributed between intracellular, extracellular, and membrane
      associated proteins, and they are mainly involved in cell communication and
      signal transduction, immune function, metabolism and energy production. This
      study provides more insights into the dynamic composition of human MFGM proteins,
      which in turn will enhance our understanding of the physiological significance of
      MFGM proteins.

PMID- 21714550
TI  - Carbon sequestration in soil by in situ catalyzed photo-oxidative polymerization
      of soil organic matter.
AB  - Here we describe an innovative mechanism for carbon sequestration in soil by in
      situ photopolymerization of soil organic matter under biomimetic catalysis. Three
      different Mediterranean soils were added with a synthetic water-soluble iron
      porphyrin, irradiated by solar light, and subjected first to 5 days incubation
      and, then, 15, and 30 wetting and drying (w/d) cycles. The in situ catalyst
      assisted photopolymerization of soil organic carbon (SOC) increased water
      stability of soil aggregates both after 5 days incubation and 15 w/d cycles, but
      not after 30 w/d cycles. Particle-size distribution of all treated soils
      confirmed the induced soil physical improvement, by showing a concomitant lower
      yield of the clay-sized fraction and larger yields of either coarse sand- or fine
      sand-size fractions, depending on soil texture, though only after 5 days
      incubation. The gain in soil physical quality was reflected by the shift of OC
      content from small to large soil aggregates, thereby suggesting that
      photopolymerization stabilized OC by both chemical and physical processes. A
      further evidence of the carbon sequestration capacity of the photocatalytic
      treatment was provided by the significant reduction of CO(2) respired by all
      soils after both incubation and w/d cycles. Our findings suggest that "green"
      catalytic technologies may potentially be the bases for future practices to
      increase soil carbon stabilization and mitigate CO(2) emissions from arable
      soils.

PMID- 21714551
TI  - Replica exchange with solute scaling: a more efficient version of replica
      exchange with solute tempering (REST2).
AB  - A small change in the Hamiltonian scaling in Replica Exchange with Solute
      Tempering (REST) is found to improve its sampling efficiency greatly, especially
      for the sampling of aqueous protein solutions in which there are large-scale
      solute conformation changes. Like the original REST (REST1), the new version
      (which we call REST2) also bypasses the poor scaling with system size of the
      standard Temperature Replica Exchange Method (TREM), reducing the number of
      replicas (parallel processes) from what must be used in TREM. This reduction is
      accomplished by deforming the Hamiltonian function for each replica in such a way
      that the acceptance probability for the exchange of replica configurations does
      not depend on the number of explicit water molecules in the system. For proof of
      concept, REST2 is compared with TREM and with REST1 for the folding of the
      trpcage and beta-hairpin in water. The comparisons confirm that REST2 greatly
      reduces the number of CPUs required by regular replica exchange and greatly
      increases the sampling efficiency over REST1. This method reduces the CPU time
      required for calculating thermodynamic averages and for the ab initio folding of
      proteins in explicit water.

PMID- 21714552
TI  - Fmoc synthesis of peptide thioesters without post-chain-assembly manipulation.
AB  - An operationally simple method for the synthesis of peptide thioesters is
      developed using standard Fmoc solid-phase peptide synthesis procedures. The
      method relies on the use of a premade enamide-containing amino acid which, in the
      final TFA cleavage step, renders the desired thioester functionality through an
      irreversible intramolecular N-to-S acyl transfer.

PMID- 21714553
TI  - Solvated interaction energy (SIE) for scoring protein-ligand binding affinities.
      2. Benchmark in the CSAR-2010 scoring exercise.
AB  - Solvated interaction energy (SIE) is an end-point physics-based scoring function
      for predicting binding affinities from force-field nonbonded interaction terms,
      continuum solvation, and configurational entropy linear compensation. We tested
      the SIE function in the Community Structure-Activity Resource (CSAR) scoring
      challenge consisting of high-resolution cocrystal structures for 343 protein
      ligand complexes with high-quality binding affinity data and high diversity with
      respect to protein targets. Particular emphasis was placed on the sensitivity of
      SIE predictions to the assignment of protonation and tautomeric states in the
      complex and the treatment of metal ions near the protein-ligand interface. These
      were manually curated from an originally distributed CSAR-HiQ data set version,
      leading to the currently distributed CSAR-NRC-HiQ version. We found that this
      manual curation was a critical step for accurately testing the performance of the
      SIE function. The standard SIE parametrization, previously calibrated on an
      independent data set, predicted absolute binding affinities with a mean-unsigned
      error (MUE) of 2.41 kcal/mol for the CSAR-HiQ version, which improved to 1.98
      kcal/mol for the upgraded CSAR-NRC-HiQ version. Half-half retraining-testing of
      SIE parameters on two predefined subsets of CSAR-NRC-HiQ led to only marginal
      further improvements to an MUE of 1.83 kcal/mol. Hence, we do not recommend
      altering the current default parameters of SIE at this time. For a sample of SIE
      outliers, additional calculations by molecular dynamics-based SIE averaging with
      or without incorporation of ligand strain, by MM-PB(GB)/SA methods with or
      without entropic estimates, or even by the linear interaction energy (LIE)
      formalism with an explicit solvent model, did not further improve predictions.

PMID- 21714556
TI  - Chemical synthesis enables biochemical and antibacterial evaluation of
      streptolydigin antibiotics.
AB  - Inhibition of bacterial transcription represents an effective and clinically
      validated anti-infective chemotherapeutic strategy. We describe the evolution of
      our approach to the streptolydigin class of antibiotics that target bacterial RNA
      polymerases (RNAPs). This effort resulted in the synthesis and biological
      evaluation of streptolydigin, streptolydiginone, streptolic acid, and a series of
      new streptolydigin-based agents. Subsequent biochemical evaluation of RNAP
      inhibition demonstrated that the presence of both streptolic acid and tetramic
      acid subunits was required for activity of this class of antibiotics. In
      addition, we identified 10,11-dihydrostreptolydigin as a new RNAP-targeting
      agent, which was assembled with high synthetic efficiency of 15 steps in the
      longest linear sequence. Dihydrostreptolydigin inhibited three representative
      bacterial RNAPs and displayed in vitro antibacterial activity against S.
      salivarius . The overall increase in synthetic efficiency combined with
      substantial antibacterial activity of this fully synthetic antibiotic
      demonstrates the power of organic synthesis in enabling design and comprehensive
      in vitro pharmacological evaluation of new chemical agents that target bacterial
      transcription.

PMID- 21714557
TI  - Physical constraints on sesquiterpene diversity arising from cyclization of the
      eudesm-5-yl carbocation.
AB  - The biogenic origins of complex cyclic terpenes derive from the interplay of
      enzymes and the intrinsic reactivity of carbocation species at major branch
      points along intramolecular cyclization pathways to ultimately determine the
      distribution of terpene skeletal types in nature. Solanaceous plants
      biosynthesize chemical defense compounds, largely derived from the eremophilane
      and spirovetivane-type sesquiterpenes. These hydrocarbon skeletons share a common
      biogenic origin, stemming from alternative Wagner-Meerwein rearrangements of the
      eudesm-5-yl carbocation during the cyclization of farnesyl pyrophosphate (FPP)
      catalyzed by sesquiterpene synthases. While the spirojatamane skeleton shares the
      same carbocation intermediate, this class of sesquiterpenes has not been reported
      in the Solanaceae and is exceedingly rare in nature. To investigate the physical
      basis for alternative rearrangements of the eudesm-5-yl carbocation, we carried
      out quantum mechanics (QM) analyses to calculate the allowable conformations,
      energies, and transition states linking conformers of the eudesm-5-yl carbocation
      to the eremophilene, spirovetivane, and spirojatamane skeletons. Additionally, we
      conducted parallel investigations on simplified decalin carbocation systems to
      examine the contribution of ring substituents to allowable conformations and
      rearrangement pathways. Our study reveals that ring substituents expand the
      conformational space accessible to the eudesm-5-yl carbocation while sterically
      blocking rearrangements in certain contexts. From our analysis, we define a
      conformational threshold for each possible rearrangement based on dihedral angles
      describing transition state geometry. Further, our calculations indicate that
      methylene migration rearrangements leading to spiro compounds are
      thermodynamically dominant in the eudesm-5-yl and simpler decalin carabocation
      systems. Interestingly, the theoretical abundance of sesquiterpene skeletal types
      arising from the intrinsic reactivity of the eudesm-5-yl carbocation stands in
      sharp contrast to their currently known natural abundance. The implications of
      these results for the catalytic tragectories catalyzed by sesquiterpene synthases
      are discussed.

PMID- 21714558
TI  - Identification of 5-7 defects in a copper oxide surface.
AB  - A topological defect in a Cu(2)O surface oxide grown on Cu(111) has been
      identified. Using scanning tunneling microscopy, we observed the formation of
      pentagonal and heptagonal rings within the Cu(2)O surface oxide. These structures
      break the symmetry of the hexagonal oxide surface and are a consequence of the
      presence of oxygen vacancies in the Cu(2)O surface. We propose that the
      pentagonal and heptagonal rings are formed through the rotation of a -O-Cu-O-
      chain in a manner similar to the Stone-Wales transformation. The proposed
      transformation is supported by the results of density functional theory
      calculations.

PMID- 21714559
TI  - View of lone electron pairs and their role in structural chemistry.
AB  - Nonbonding valence electrons, better known as lone pairs, are found in all anions
      as well as in cations in their lower oxidation states. In this paper the
      properties of lone pairs are analyzed using a bond valence model defined in terms
      of a core-and-valence-shell picture, which can be reduced to the point charges of
      the ionic model. A bond is defined in terms of the electrostatic flux linking the
      atoms. When the lone pairs are inactive, they are uniformly distributed around
      the valence shell and the ion behaves like a main group ion that has no lone
      pairs. In this state it can be assigned a bonding strength that obeys the valence
      matching rule (for stable bonds the cation and anion bonding strengths should not
      differ by more than a factor of 2). However, when an ion with a lone pair has a
      bonding strength less than half that of the counterion, it has the flexibility to
      form a stronger bond by converting lone pair electron density to bonding electron
      density in the region where the valence shells overlap. To conserve the number of
      lone pairs, bonding electron density elsewhere in the valence shell is converted
      to lone pairs. The result is the adoption of an anisotropic coordination
      environment with fewer bonds but bonds whose enhanced strength matches the higher
      bonding strength of the counterion. This analysis raises questions about the
      validity of a number of traditional ideas on the nature of chemical bonds. It
      shows that lone pairs do not form dative bonds. In a neutral molecule, the base
      function that is often attributed to a lone pair is always accompanied by an acid
      function, and both functions must be simultaneously activated. Electron-pair
      bonds, which are found only around strongly bonding cations, normally result in
      the formation of molecules, explaining why the models developed to describe
      molecular structures are unable to give good descriptions of extended crystal
      structures.

PMID- 21714560
TI  - Characterization of a trihydrogen bond on the basis of the topology of the
      electron density.
AB  - Recent DFT calculations have predicted unexpected molecular structures for the
      ion induced dipole clusters H(n)(-) (3 <= n-odd <= 13). Analysis of these
      calculations suggests the definition of a new bond, called the trihydogen bond
      (THB). This is placed in context by a review and classification of multihydrogen
      interactions as usually discussed in the literature. The results of analysis
      related to the trihydrogen bond are presented. These include a series of linear
      relations exhibited by the H(n)(-) clusters involving the charge carried by the
      central H(-) ion, the binding energy of the clusters, and the relative
      stabilization of the central anion H(-) with respect to the energy of a free H(-)
      atom.

PMID- 21714561
TI  - Application of the atoms in molecules theory and computational chemistry in mass
      spectrometry analysis of 1,4-naphthoquinone derivatives.
AB  - Mass spectrometry analysis of 2-(acylamino)-1,4-naphthoquinone derivatives was
      carried out using electrospray ionization ion source in combination with tandem
      mass spectrometry. Protonated molecules were dissociated by application of the
      collision-induced dissociation (CID), and the protonation sites were suggested on
      the basis of the HOMO, molecular electrostatic potential map (MEP), proton
      affinity, and Fukui functions calculated by B3LYP/6-31+G(d,p). The main
      fragmentation mechanisms undergone by the protonated ions were elucidated on the
      basis of energy, geometry, and topology analysis of equilibrium geometries.
      Compounds exhibiting only aliphatic hydrogens at the lateral chain undergo
      interesting ketene elimination. On the other hand, only the benzoylium ion
      formation is detected for 2-benzoylamino-1,4-naphthoquinone. The bonds geometric
      and atoms in molecules parameters give evidence that acidic hydrogen atoms play
      an important role in the fragmentation pathways.

PMID- 21714562
TI  - Identification and physicochemical characterization of BldR2 from Sulfolobus
      solfataricus, a novel archaeal member of the MarR transcription factor family.
AB  - The multiple antibiotic resistance regulators (MarR) constitute a family of
      ligand-responsive transcriptional regulators abundantly distributed throughout
      the bacterial and archaeal domains. Here we describe the identification and
      characterization of BldR2, as a new member of this family, in the archaeon
      Sulfolobus solfataricus and report physiological, biochemical, and biophysical
      investigation of its stability and DNA binding ability. Transcriptional analysis
      revealed the upregulation of BldR2 expression by aromatic compounds in the late
      logarithmic growth phase and allowed the identification of cis-acting sequences.
      Our results suggest that BldR2 possesses in solution a dimeric structure and a
      high stability against both temperature and chemical denaturing agents; the
      protein binds site specifically to its own promoter, Sso1082, with a micromolar
      binding affinity at two palindromic sites overlapping TATA-BRE and the
      transcription start site. Benzaldehyde and salicylate, ligands of MarR members,
      are antagonists of binding of DNA by BldR2. Moreover, two single-point mutants of
      BldR2, R19A and A65S, properly designed for obtaining information about the
      dimerization and the DNA binding sites of the protein, have been produced and
      characterized. The results point out an involvement of BldR2 in the regulation of
      the stress response to aromatic compounds and point to arginine 19 as a key amino
      acid involved in protein dimerization, while the introduction of serine 65
      increases the DNA affinity of the protein, making it comparable with those of
      other members of the MarR family.

PMID- 21714563
TI  - Phenolic composition of the Brazilian seedless table grape varieties BRS Clara
      and BRS Morena.
AB  - The detailed phenolic composition (anthocyanins, flavonols, hydroxycinnamic acid
      derivatives, stilbenes, and flavan-3-ols) in the skin and flesh of the new BRS
      Clara and BRS Morena seedless table grapes has been studied using HPLC-DAD-ESI
      MS/MS. The two grapes, especially BRS Morena, contained high amounts of phenolic
      compounds, mainly located in their skins and qualitatively not different from
      those found in Vitis vinifera grapes. In addition, BRS Morena (a teinturier
      variety) showed qualitatively different phenolic compositions in its skin and
      flesh, mainly affecting the anthocyanin and flavonol profiles. Consistent with
      high phenolic contents, high antioxidant capacity values were registered for both
      grape varieties, especially for BRS Morena. Proanthocyanidins and
      hydroxycinnamoyl-tartaric acids were the major phenolic compounds found in BRS
      Clara and were also important in BRS Morena, although anthocyanins were the main
      phenolic compounds in the latter case. These results suggest that the entire
      grapes, including the skin, may potentially possess properties that are
      beneficial to human health. In this context, the BRS Morena grape can be
      considered as a high resveratrol producer.

PMID- 21714564
TI  - Biosynthetic studies of the notoamides: isotopic synthesis of stephacidin A and
      incorporation into notoamide B and sclerotiamide.
AB  - The advanced natural product stephacidin A is proposed as a biosynthetic
      precursor to notoamide B in various Aspergillus species. Doubly (13)C-labeled
      racemic stephacidin A was synthesized and fed to cultures of the terrestrial
      derived fungus, Aspergillus versicolor NRRL 35600, and the marine-derived fungus,
      Aspergillus sp. MF297-2. Analysis of the metabolites revealed enantiospecific
      incorporation of intact (-)-stephacidin A into (+)-notoamide B in Aspergillus
      versicolor and (+)-stephacidin A into (-)-notoamide B in Aspergillus sp. MF297-2.
      (13)C-Labeled sclerotiamide was also isolated from both fungal cultures.

PMID- 21714565
TI  - Covalent binding of single-walled carbon nanotubes to polyamide membranes for
      antimicrobial surface properties.
AB  - We propose an innovative approach to impart nanomaterial-specific properties to
      the surface of thin-film composite membranes. Specifically, biocidal properties
      were obtained by covalently binding single-walled carbon nanotubes (SWNTs) to the
      membrane surface. The SWNTs were first modified by purification and ozonolysis to
      increase their sidewall functionalities, maximize cytotoxic properties, and
      achieve dispersion in aqueous solution. A tailored reaction protocol was
      developed to exploit the inherent moieties of hand-cast polyamide membrane
      surfaces and create covalent amide bonds with the functionalized SWNTs. The
      reaction is entirely aqueous-based and entails activation of the carboxylate
      groups of both the membrane and the nanomaterials to maximize reaction with
      ethylenediamine. The presence of SWNTs was verified after sonication of the
      membranes, confirming the strength of the bond between the SWNTs and the membrane
      surface. Characterization of the SWNT-functionalized surfaces demonstrated the
      attainment of membranes with novel properties that continued to exhibit high
      performance in water separation processes. The presence of surface-bound
      antimicrobial SWNTs was confirmed by experiments using E. coli cells that
      demonstrated an enhanced bacterial cytotoxicity for the SWNT-coated membranes.
      The SWNT membranes were observed to achieve up to 60% inactivation of bacteria
      attached to the membrane within 1 h of contact time. Our results suggest the
      potential of covalently bonded SWNTs to delay the onset of membrane biofouling
      during operation.

PMID- 21714566
TI  - Thermo-msf-parser: an open source Java library to parse and visualize Thermo
      Proteome Discoverer msf files.
AB  - The Thermo Proteome Discoverer program integrates both peptide identification and
      quantification into a single workflow for peptide-centric proteomics.
      Furthermore, its close integration with Thermo mass spectrometers has made it
      increasingly popular in the field. Here, we present a Java library to parse the
      msf files that constitute the output of Proteome Discoverer. The parser is also
      implemented as a graphical user interface allowing convenient access to the
      information found in the msf files, and in Rover, a program to analyze and
      validate quantitative proteomics information. All code, binaries, and
      documentation is freely available at http://thermo-msf-parser.googlecode.com.

PMID- 21714567
TI  - Identification of alternative binding sites for inhibitors of HIV-1 ribonuclease
      H through comparative analysis of virtual enrichment studies.
AB  - The ribonuclease H (RNase H) domain on the p66 monomer of HIV-1 reverse
      transcriptase enzyme has become a target for inhibition. The active site is one
      potential binding site, but other RNase H sites can accommodate inhibitors. Using
      a combination of experimental and computational studies, potential new binding
      sites and binding modes have been identified. Libraries of compounds were
      screened with an experimental assay to identify actives without knowledge of the
      binding site. The compounds were computationally docked at putative binding
      sites. Based on positive enrichment of natural-product actives relative to the
      database of compounds, we propose that many inhibitors bind to an alternative,
      potentially allosteric, site centered on Q507 of p66. For a series of hydrazone
      compounds, a small amount of positive enrichment was obtained when active
      compounds were bound by induced-fit docking at the interface between the DNA:RNA
      substrate and the RNase H domain near residue Q500.

PMID- 21714568
TI  - Soil water availability in rainfed cultivation affects more than cultivar some
      nutraceutical components and the sensory profile of virgin olive oil.
AB  - This research considered the varieties 'Frantoio' and 'Moraiolo' growing in
      rainfed olive trees (Olea europaea) and took place in Tuscany, central Italy.
      Soil moisture was monitored during the very meteorologically contrasting years
      2002 and 2003 in two nearby olive groves. The plots had the same morphological
      and climatic conditions, but different soil types. Monocultivar oil samples were
      analyzed to determine fatty acids, minor polar compounds, and tocopherols content
      and were submitted to organoleptic analysis by a panel of trained tasters. The
      results highlighted that soil water regimen affects some nutraceutical components
      and the sensory evaluation of olive oil. Cultivar also affected yield components,
      polyphenols, and tocopherols content, but less than soil water availability. The
      plants on the soil inducing a relatively more intense and longer water deficit
      during summer (a Skeleti Calcaric Regosol) had an early ripening and gave the
      best results in terms of phenolic compounds and, consequently, antioxidant
      properties of the olive oil. The sensorial properties of the oil obtained from
      both cultivars on the Regosol were superior in both years of the trial.

PMID- 21714569
TI  - Improved hemocompatibility and endothelialization of vascular grafts by covalent
      immobilization of sulfated silk fibroin on poly(lactic-co-glycolic acid)
      scaffolds.
AB  - Endothelialization of vascular grafts prior to implantation has been investigated
      widely to enhance biocompatibility and antithrombogenicity. Thrombosis of
      artificial vessels is typically caused by platelet adhesion and agglomeration
      following endothelial cells detachment when exposed to the shear stress of blood
      circulation. The present study thus aimed at preventing platelet adhesion and
      aggregation onto biomaterials before the endothelial confluence is fully
      achieved. We report this modification of poly(lactic-co-glycolic acid) (PLGA)
      scaffolds, both to impart hemocompatibility to prevent platelet adhesion and
      aggregation before the endothelial confluence is fully achieved and to support EC
      growth to accelerate endothelialization. The modification was achieved by
      covalent immobilization of sulfated silk fibroin on PLGA scaffolds using gamma
      irradiation. Using phosphate-buffered saline (PBS) as an aging medium, it was
      demonstrated that the scaffolds prepared by gamma irradiation had a good
      retention of sulfated silk fibroin. The systematic in vitro hemocompatibility
      evaluation revealed that sulfated silk fibroin covalently immobilized PLGA (S
      PLGA) scaffolds-reduced platelet adhesion and activation, prolonged whole blood
      clotting time, activated partial thromboplastin time (APTT), thrombin time (TT),
      and prothrombin time (PT). To evaluate further in vitro cytocompatibility of the
      scaffolds, we seeded vascular ECs on the scaffolds and cultured them for 2 weeks.
      The ECs were seen to attach and proliferate well on S-PLGA scaffolds, forming
      cell aggregates that gradually increased in size and fused with adjacent cell
      aggregates to form a monolayer covering the scaffold surface. Moreover, it was
      demonstrated through the gene transcript levels and the protein expressions of EC
      specific markers that the cell functions of ECs on S-PLGA scaffolds were better
      preserved than those on PLGA scaffolds. Therefore, this study has described the
      generation of a vascular graft that possesses the unique ability to display
      excellent hemocompatibility while simultaneously supporting extensive
      endothelialization.

PMID- 21714570
TI  - De novo designed protein transduction domain mimics from simple synthetic
      polymers.
AB  - Protein transduction domains (PTDs) that readily transverse cellular membranes
      are of great interest and are attractive tools for the intracellular delivery of
      bioactive molecules. Learning to program synthetic polymers and oligomers with
      the appropriate chemical information to capture adequately the biological
      activity of proteins is critical to our improved understanding of how these
      natural molecules work. In addition, the versatility of these synthetic mimics
      provides the opportunity to discover analogs with superior properties compared
      with their native sequences. Here we report the first detailed structure-activity
      relationship of a new PTD family of polymers based on a completely abiotic
      backbone. The synthetic approach easily allows doubling the density of guanidine
      functional groups, which increases the transduction efficiency of the sequences.
      Cellular uptake studies on three different cell lines (HEK 293T, CHO, and Jurkat
      T cells) confirm that these synthetic analogs are highly efficient novel protein
      transduction domain mimics (PTDMs), which are more effective than TAT(49-57) and
      nonaarginine (R9) and also highlight the usefulness of polymer chemistry at the
      chemistry-biology interface.

PMID- 21714571
TI  - Life cycle assessment of Chinese shrimp farming systems targeted for export and
      domestic sales.
AB  - We conducted surveys of six hatcheries and 18 farms for data inputs to complete a
      cradle-to-farm-gate life cycle assessment (LCA) to evaluate the environmental
      performance for intensive (for export markets in Chicago) and semi-intensive (for
      domestic markets in Shanghai) shrimp farming systems in Hainan Province, China.
      The relative contribution to overall environmental performance of processing and
      distribution to final markets were also evaluated from a cradle-to-destination
      port perspective. Environmental impact categories included global warming,
      acidification, eutrophication, cumulative energy use, and biotic resource use.
      Our results indicated that intensive farming had significantly higher
      environmental impacts per unit production than semi-intensive farming in all
      impact categories. The grow-out stage contributed between 96.4% and 99.6% of the
      cradle-to-farm-gate impacts. These impacts were mainly caused by feed production,
      electricity use, and farm-level effluents. By averaging over intensive (15%) and
      semi-intensive (85%) farming systems, 1 metric ton (t) live-weight of shrimp
      production in China required 38.3 +/- 4.3 GJ of energy, as well as 40.4 +/- 1.7 t
      of net primary productivity, and generated 23.1 +/- 2.6 kg of SO(2) equiv, 36.9
      +/- 4.3 kg of PO(4) equiv, and 3.1 +/- 0.4 t of CO(2) equiv. Processing made a
      higher contribution to cradle-to-destination-port impacts than distribution of
      processed shrimp from farm gate to final markets in both supply chains. In 2008,
      the estimated total electricity consumption, energy consumption, and greenhouse
      gas emissions from Chinese white-leg shrimp production would be 1.1 billion kW.h,
      49 million GJ, and 4 million metric tons, respectively. Improvements suggested
      for Chinese shrimp aquaculture include changes in feed composition, farm
      management, electricity-generating sources, and effluent treatment before
      discharge. Our results can be used to optimize market-oriented shrimp supply
      chains and promote more sustainable shrimp production and consumption.

PMID- 21714572
TI  - Phosphate bonding on noncrystalline Al/Fe-hydroxide coprecipitates.
AB  - Poorly crystalline minerals have high sorption capacities for environmentally
      important chemical species, but molecular-level mechanisms of sorption on complex
      mineral assemblages remain largely unknown. We determined the distribution of
      orthophosphate (PO(4)) bonding between Al and Fe in relation to structural
      properties of Al/Fe-hydroxide coprecipitates. Phosphate was sorbed at
      concentrations between 0.042 and 0.162 mol P mol(-1) Al+Fe on coprecipitates
      containing 0, 20, 50, 75, or 100 mol % of metal as Al. Phosphorus XANES analyses
      showed preferential bonding of PO(4) for Al on coprecipitates with 20 and 50 mol
      % Al, and no preference for either metal at 75 mol % Al, consistent with X-ray
      photoelectron spectroscopy (XPS) analyses of near-surface metal distributions.
      Structural ordering and the Fe-hydroxide domain size in coprecipitates decreased
      with increasing Al proportion, as shown by X-ray diffraction (XRD) and Fe EXAFS
      analyses. Structural interactions in coprecipitates imparted unique PO(4)
      sorption properties compared with isolated Al- or Fe-hydroxide.

PMID- 21714573
TI  - Chemometric classification of the fat residues from the conditioning operations
      of table olive processing, based on their minor components.
AB  - The work characterizes the unsaponifiable matter of fats released in pitting
      green (GP) and ripe (RP) olives, in pitting/stuffing green olives with vegetable
      (GPSV) and animal (GPSA) products and in the fat settled at the end of the
      factory sewer system (W). The unsaponifiable matter ranged from 1.94% (RP) to
      5.91% (GPSA); total sterols from 1319 mg/kg fat (GPSV) to 2002 mg/kg fat (RP),
      with beta-sitosterol as the most abundant. Fatty alcohols ranged from 242 mg/kg
      (GP) to 556 mg/kg (W), with C22 as the most abundant. Triterpene diols were found
      only in GPSV (erythrodiol + uvaol, 0.80%). Wax was not present in the fats from
      GP and RP but increased with the general fat degradation in the order GPSV (128
      mg/kg), GPSA (171 mg/kg) and W (263 mg/kg). Chemometric analysis was able to
      detect differences among the diverse fats; sterols + fatty alcohols cluster
      analysis was useful for fat grouping.

PMID- 21714574
TI  - Sensing amyloid-beta aggregation using luminescent dipyridophenazine
      ruthenium(II) complexes.
AB  - The aggregation of amyloid-beta (Abeta) peptides has been associated with the
      onset of Alzheimer's disease. Here, we report the use of a luminescent
      dipyridophenazine ruthenium(II) complex to monitor Abeta fibrillization. This
      complex is not photoluminescent in aqueous solution nor in the presence of
      monomeric Abeta, but it presents a strong photoluminescence in the presence of
      Abeta fibril aggregates. One of the advantages of this metal complex is its large
      Stokes shift (180 nm). Furthermore, the long-lived photoluminescence lifetime of
      this ruthenium complex allows its use for the detection of fibrillar proteins in
      the presence of short-lived fluorescent backgrounds, using time-gating
      technology. We will present evidence of the advantages of dipyridophenazine
      ruthenium(II) complexes for monitoring protein fibrillization in highly
      fluorescent media.

PMID- 21714575
TI  - Polyisobutylene-supported phosphines as recyclable and regenerable catalysts and
      reagents.
AB  - Phosphines are important as catalysts or reagents in synthesis but must be
      separated from products after a reaction. This report shows that polyisobutylene
      (PIB)-bound alkyldiaryl- and triarylphosphines are useful as catalysts in
      addition and allylic amination reactions or as reagents in aza-Wittig and
      Mitsunobu reactions. Heptane solutions of such phosphines and their oxidized
      byproducts can be easily separated from polar solutions of organic products, and
      PIB-phosphine oxides formed during a reaction can readily be reduced to PIB
      phosphines for reuse.

PMID- 21714576
TI  - One-pot synthesis of (E)-styryl ketones from styrenes.
AB  - A new, efficient protocol for the highly stereoselective one-pot synthesis of (E)
      styryl ketones from styrenes based on sequential ruthenium-catalyzed silylative
      coupling-rhodium-catalyzed desilylative acylation reactions is reported.

PMID- 21714577
TI  - Luminescent gold nanoparticles with pH-dependent membrane adsorption.
AB  - pH regulates many cellular processes and is also an indicator of disease
      progression. Therefore, pH-responsive materials often serve as either tools in
      the fundamental understanding of cell biology or medicine for disease diagnosis
      and therapy. While gold nanoparticles have broad biomedical applications, very
      few of them exhibit pH-dependent interactions with live cells in a native
      biological environment due to nonspecific serum protein adsorption. Herein, we
      report that by coating luminescent gold nanoparticles with a natural peptide,
      glutathione, and the simplest stable aminothiol, cysteamine, we enabled the
      nanoparticles to exhibit not only high resistance to serum protein adsorption but
      also pH-dependent adsorption onto live cell membranes in the presence of serum
      proteins. Incorporating this pH-dependent membrane adsorption behavior into gold
      nanoparticles could potentially catalyze new biomedical applications of metal
      nanoparticles in the fundamental understanding of biological processes as well as
      disease diagnosis and therapy, where pH changes are involved.

PMID- 21714578
TI  - Biomass characterization of morphological portions of alamo switchgrass.
AB  - Comparative studies between the leaf and internode portions of switchgrass,
      Panicum virgatum L., were performed by compositional analysis and structural
      determination. GC-MS, ICP, and HPAEC-PAD were employed to analyze the chemical
      compositions of the fractionated switchgrass samples. Quantitative (13)C NMR and
      CP/MAS (13)C NMR techniques were employed to determine the structures of lignin
      and cellulose, respectively. These results indicated that the leaves and
      internodes differed chemically in the amounts of inorganic elements, hot-water
      extractives, benzene/ethanol extractives, carbohydrates, and lignin content.
      However, the ultrastructure of isolated cellulose was comparable between leaves
      and internodes. Ball-milled lignins isolated from leaves and internodes were
      found to have H/G/S ratios of 12.4/53.9/33.7 and 8.6/54.8/36.6, respectively.

PMID- 21714579
TI  - Treatment options for hyperhidrosis.
AB  - Hyperhidrosis is a disorder of excessive sweating beyond what is expected for
      thermoregulatory needs and environmental conditions. Primary hyperhidrosis has an
      estimated prevalence of nearly 3% and is associated with significant medical and
      psychosocial consequences. Most cases of hyperhidrosis involve areas of high
      eccrine density, particularly the axillae, palms, and soles, and less often the
      craniofacial area. Multiple therapies are available for the treatment of
      hyperhidrosis. Options include topical medications (most commonly aluminum
      chloride), iontophoresis, botulinum toxin injections, systemic medications
      (including glycopyrrolate and clonidine), and surgery (most commonly endoscopic
      thoracic sympathectomy [ETS]). The purpose of this article is to comprehensively
      review the literature on the subject, with a focus on new and emerging treatment
      options. Updated therapeutic algorithms are proposed for each commonly affected
      anatomic site, with practical procedural guidelines. For axillary and
      palmoplantar hyperhidrosis, topical treatment is recommended as first-line
      treatment. For axillary hyperhidrosis, botulinum toxin injections are recommended
      as second-line treatment, oral medications as third-line treatment, local surgery
      as fourth-line treatment, and ETS as fifth-line treatment. For palmar and plantar
      hyperhidrosis, we consider a trial of oral medications (glycopyrrolate 1-2 mg
      once or twice daily preferred to clonidine 0.1 mg twice daily) as second-line
      therapy due to the low cost, convenience, and emerging literature supporting
      their excellent safety and reasonable efficacy. Iontophoresis is considered third
      line therapy for palmoplantar hyperhidrosis; efficacy is high although so are the
      initial levels of cost and inconvenience. Botulinum toxin injections are
      considered fourth-line treatment for palmoplantar hyperhidrosis; efficacy is high
      though the treatment remains expensive, must be repeated every 3-6 months, and is
      associated with pain and/or anesthesia-related complications. ETS is a fifth-line
      option for palmar hyperhidrosis but is not recommended for plantar hyperhidrosis
      due to anatomic risks. For craniofacial hyperhidrosis, oral medications (either
      glycopyrrolate or clonidine) are considered first-line therapy. Topical
      medications or botulinum toxin injections may be useful in some cases and ETS is
      an option for severe craniofacial hyperhidrosis.

PMID- 21714580
TI  - Estrogen and skin: therapeutic options.
AB  - Aging of the skin is associated with skin thinning, atrophy, dryness, wrinkling,
      and delayed wound healing. These undesirable aging effects are exacerbated by
      declining estrogen levels in postmenopausal women. With the rise in interest in
      long-term postmenopausal skin management, studies on the restorative benefits
      that estrogen may have on aged skin have expanded. Systemic estrogen replacement
      therapy (ERT) has been shown to improve some aspects of skin. Estrogen restores
      skin thickness by increasing collagen synthesis while limiting excessive collagen
      degradation. Wrinkling is improved following estrogen treatment since estrogen
      enhances the morphology and synthesis of elastic fibers, collagen type III, and
      hyaluronic acids. Dryness is also alleviated through increased water-holding
      capacity, increased sebum production, and improved barrier function of the skin.
      Furthermore, estrogen modulates local inflammation, granulation, re
      epithelialization, and possibly wound contraction, which collectively accelerates
      wound healing at the expense of forming lower quality scars. Despite its
      promises, long-term ERT has been associated with harmful systemic effects. In the
      search for safe and effective alternatives with more focused effects on the skin,
      topical estrogens, phytoestrogens, and tissue-specific drugs called selective
      estrogen receptor modulators (SERMs) have been explored. We discuss the promises
      and challenges of utilizing topical estrogens, SERMs, and phytoestrogens in
      postmenopausal skin management.

PMID- 21714581
TI  - Effect of multiple oral doses of linagliptin on the steady-state pharmacokinetics
      of a combination oral contraceptive in healthy female adults: an open-label, two
      period, fixed-sequence, multiple-dose study.
AB  - BACKGROUND: Linagliptin is an oral dipeptidyl peptidase (DPP)-4 inhibitor that
      has been recently approved for the treatment of type 2 diabetes mellitus.
      Microgynon(r) 30 is a combined oral contraceptive pill containing both
      ethinylestradiol 30 MUg and levonorgestrel 150 MUg (EE 30 MUg/LNG 150 MUg).
      OBJECTIVE: The objective of this study was to determine the effect of multiple
      doses of linagliptin (5 mg once daily) on the steady-state pharmacokinetics of EE
      and LNG following once-daily doses of EE 30 MUg/LNG 150 MUg. METHODS: This was an
      open-label, two-period, fixed-sequence, multiple-dose study, consisting of a run
      in period, a 14-day reference treatment period and a 7-day test treatment period.
      The study recruited 18 healthy pre-menopausal female subjects aged 18-40 years
      with a body mass index of 18.5-27.0 kg/m2. Only women with regular menstrual
      cycles were included in this study. The treatment sequence was divided into three
      steps: an individually tailored run-in period with EE 30 MUg/LNG 150 MUg to
      synchronize the menstrual cycles of the subjects followed by a washout period of
      7 days; the reference treatment period, during which EE 30 MUg/LNG 150 MUg alone
      was taken on days 1-14; and the test treatment period, during which EE 30 MUg/LNG
      150 MUg plus linagliptin were taken on days 15-21. The pharmacokinetic parameters
      measured were maximum steady-state plasma concentration during a dosage interval
      (C(max,ss)), time to reach maximum plasma concentration following administration
      at steady state (t(max,ss)) and area under the plasma concentration-time curve
      during a dosage interval (tau) at steady state (AUC(tau,ss)). RESULTS: The
      AUC(tau,ss) and C(max,ss) of EE and LNG were comparable when EE 30 MUg/LNG 150
      MUg was given alone or combined with linagliptin. The adjusted geometric mean
      ratios for AUC(tau,ss) and C(max,ss) of EE following EE 30 MUg/LNG 150 MUg plus
      linagliptin versus EE 30 MUg/LNG 150 MUg alone were 101.4 (90% CI 97.2, 105.8)
      and 107.8 (90% CI 99.7, 116.6), respectively. The adjusted geometric mean ratios
      for AUC(tau,ss) and C(max,ss) of LNG following EE 30 MUg/LNG 150 MUg plus
      linagliptin versus EE 30 MUg/LNG 150 MUg alone were 108.8 (90% CI 104.5, 113.3)
      and 113.5 (90% CI 106.1, 121.3), respectively. The combination was well
      tolerated. CONCLUSION: Linagliptin had no clinically relevant effect on the
      steady-state pharmacokinetics of EE and LNG in healthy female subjects, and the
      combination of EE 30 MUg/LNG 150 MUg and linagliptin was well tolerated in this
      study. Therefore, linagliptin has the potential to be used in the treatment of
      female patients with type 2 diabetes in combination with oral contraceptives
      containing these components, such as EE 30 MUg/LNG 150 MUg. TRIAL REGISTRATION:
      The EudraCT number for this study is 2008-000953-37.

PMID- 21714582
TI  - Determinants of antenatal and postnatal care visits among Indigenous people in
      Bangladesh: a study of the Mru community.
AB  - INTRODUCTION: Antenatal and postnatal care services are significant interventions
      to improve maternal health and prevent maternal and infant deaths. However, these
      services are poorly developed in Bangladesh, particularly among Indigenous women.
      This study examined factors associated with antenatal and postnatal care visits
      among the Mru, the most underprivileged Indigenous people in Bangladesh. METHODS:
      This cross-sectional study used both quantitative and qualitative methods. In
      total, 374 currently married Mru women with at least one child aged 5 years or
      younger were selected from 3 upazilas (sub-districts) of Bandarban District,
      Bangladesh for survey. In addition, in-depth interviews were performed with 26
      Mru leaders, Mru women, traditional midwives, village 'doctors', school teachers,
      health and non-government organization workers. Associations between antenatal
      and postnatal care visits and the women's backgrounds characteristics were
      assessed by bivariate and multivariate analyses. RESULTS: The traditional Mru
      prenatal and postnatal practices potentially inhibited women from seeking care.
      Both antenatal (11.2%) and postnatal (6.4%) care visits among the Mru women were
      lower than the national level. Most visits were to traditional midwives in their
      rural villages, rather than to health complexes or hospitals. The main reasons
      for lack of antenatal and postnatal care were travelling distance to care and
      transportation problems. Multivariate analysis revealed factors associated with
      antenatal care were the respondent's place of residence, age, level of education,
      distance to the service centers and exposure to any mass media. Similar results
      were obtained with regard to postnatal care visits. CONCLUSIONS: This study
      suggests that cultural issues, distance, infrastructure and socioeconomic status
      are important determinants of maternal healthcare-seeking behavior. Healthcare
      delivery systems and appropriate education programs should be developed at the
      village level to improve the health of mothers and children in the Mru community.

PMID- 21714583
TI  - Decompressive craniectomy--time for a change?

PMID- 21714584
TI  - Cervical synovial sarcoma necessitating multiple neurosurgical procedures.
AB  - Synovial sarcoma is a rare mesenchymal tumour with the worst prognosis among soft
      tissue tumours. Although chemosensitive, it can only be cured by complete
      surgical resection, often limited by its anatomical relations. We present a
      patient with a cervical synovial sarcoma. Three operations were performed
      followed by equal recurrences.

PMID- 21714585
TI  - The effects of rosuvastatin alone or in combination with fenofibrate or omega 3
      fatty acids on inflammation and oxidative stress in patients with mixed
      dyslipidemia.
AB  - OBJECTIVE: Mixed dyslipidemia, oxidative stress and inflammation are related to a
      high risk for cardiovascular events. The aim of this open-label randomized study
      was to compare the effects of high-dose rosuvastatin, low-dose rosuvastatin plus
      fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation
      and oxidative stress indices in patients with mixed dyslipidemia. METHODS: Ninety
      patients with mixed dyslipidemia participated in the study. Patients were
      randomly allocated to receive rosuvastatin 40 mg (n = 30, group R), rosuvastatin
      10 mg plus fenofibrate 200 mg (n = 30, group RF) or rosuvastatin 10 mg plus omega
      3 fatty acids 2 g daily (n = 30, group ROmega). Plasma and high-density
      lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 (LpPLA2)
      activities, high-sensitivity C reactive protein (hsCRP), plasma isoprostane and
      paraoxonase (PON1) activities were measured at baseline and after 3 months of
      treatment. RESULTS: Serum concentrations of non-HDL cholesterol and low-density
      lipoprotein cholesterol (LDL-C) were significantly reduced in all study groups.
      However, these changes were more pronounced in the rosuvastatin monotherapy
      group. In all treatment groups a significant reduction in total plasma LpPLA2
      activity was observed (by 41, 38 and 30% for groups R, RF and ROmega,
      respectively). This decrease was greater in the R and RF groups compared with the
      ROmega combination (p < 0.05). HDL-LpPLA2 activity was increased more in the RF
      group (+43%) compared with the R and ROmega groups (+ 18% and + 35%,
      respectively; p < 0.05 for both comparisons). In all treatment groups there was a
      nonsignificant reduction in plasma 8-iso-PGF2alpha levels. A 53% reduction of
      hsCRP levels was observed in the R group, while in the RF and ROmega groups the
      reduction was 28 and 23%, respectively (p < 0.05 and p < 0.01 for the comparisons
      of group R with groups RF and ROmega, respectively). No significant changes were
      observed in PON activities in all treatment groups. CONCLUSION: The greater non
      HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its
      more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen
      is a better treatment option for patients with mixed dyslipidemia.

PMID- 21714586
TI  - Therapy for prevention of post-stroke depression.
AB  - INTRODUCTION: Depression is the most common psychiatric disorder after stroke
      that adversely affects stroke outcomes. It is often underdiagnosed and
      inadequately treated. Hence, there is growing interest in interventions to
      prevent depression in stroke patients, which is in concert with emerging data
      that indicate prevention of major depression in selective high-risk populations
      may be effective. AREAS COVERED: This article reviews the state of the current
      literature on pharmacologic and psychosocial preventive intervention strategies
      for depression in stroke patients. EXPERT OPINION: The emerging data indicate
      that antidepressants and psychological therapies may be effective and safe in
      preventing post-stroke depression. More well-designed preventive trials are
      required to determine the efficacy and cost-effectiveness of preventive
      interventions targeting stroke patients, who are a high-risk group for
      depression.

PMID- 21714587
TI  - Contemporary surgical treatment of hidradenitis suppurativa (HS) with a focus on
      the use of the diode hair laser in a case.
AB  - Hidradenitis suppurativa, a chronic recurrent disorder, characterized by painful,
      deep-seated nodules and abscesses commonly affecting the pilosebaceous-apocrine
      unit of the axillary, inguinal and mammary region in females, while the perianal
      area and buttocks are the prevalent sites in males. Its onset is after puberty,
      and may persist thereafter. Its exact aetiology is speculative. Follicular
      occlusion is the primary event leading to secondary inflammation, infection and
      destruction of the unit, ultimately affecting the adjoining subcutaneous tissue.
      Smoking and obesity may trigger or aggravate the condition. Stage of disease
      determines the mode of treatment. Medical treatment is valid in the early stage,
      but the results are transient. The early stage may warrant incision, and drainage
      of abscesses coupled with limited excision for locally recurring draining
      sinuses. While radical excision and healing with secondary intention, skin
      grafting, and flaps is recommended in advanced stages, laser therapy including
      the diode laser may prove a promising and innovative alternative.

PMID- 21714588
TI  - Punch excision combined with erbium:YAG fractional laser: its application on
      different types of scars in Asian patients (a pilot study).
AB  - Scars cause significant impact on the quality of life of the affected patients
      and compel the search for more effective treatments. Ablative laser skin
      resurfacing, either alone or in combination with other modalities, is the gold
      standard for treating various scars but is associated with prolonged recovery and
      many side effects. To address these limitations, newer modalities employing the
      principle of fractional photothermolysis have emerged. Herein, we investigated
      the combined effect of punch excision and the erbium:YAG (Er:YAG) fractional
      laser on different types of scars in Asian individuals.

PMID- 21714589
TI  - Mechanical stability assessment of novel orthodontic mini-implant designs: Part
      2.
AB  - OBJECTIVE: To assess the mechanical stability of a newly revised orthodontic mini
      implant design (N2) compared with a design introduced in Part 1 of the study (N1)
      and the most widely-used commercially-available design (CA). To evaluate the mean
      buccal bone thickness of maxillary and mandibular posterior teeth using cone-beam
      computed tomography (CBCT). MATERIALS AND METHODS: From the CBCT scans of 20
      patients, six tomographic cross-sections were generated for each tooth. Buccal
      bone thickness was measured from the most convex point on the bone to the root
      surface. CA (1.5 mm in diameter and 6 mm in length), N1, and N2 (shorter and
      narrower than N1) were inserted in simulated bone with cortical and trabecular
      bone layers. Mechanical stability was compared in vitro through torque and
      lateral displacement tests. RESULTS: The bone thickness ranged from 2.26 to 3.88
      mm. Maximum insertion torque was decreased significantly in N2 compared to N1.
      However, force levels for all displacement distances and torque ratio were the
      highest in N2, followed by N1 and CA (alpha = .05). CONCLUSIONS: Both torque and
      lateral displacement tests highlighted the enhanced stability of N2 compared with
      CA. Design revisions to N1 effectively mitigated N1's high insertion torque and
      thus potentially reduced microdamage to the surrounding bone. The N2 design is
      promising as evidenced by enhanced stability and high mechanical efficiency.
      Moreover, N2 is not limited to placement in interradicular spaces and has the
      capacity to be placed in the buccal bone superficial to the root surface with
      diminished risk of endangering nearby anatomic structures during placement and
      treatment.

PMID- 21714590
TI  - CX3CR1 as a target for airways inflammation.
AB  - Inflammation is a key component of asthma. Membrane-bound chemokine CX3CL1 is
      markedly induced on endothelial cells by inflammatory cytokines, and CX3CL1
      levels are elevated in the bronchoalveolar lavage (BAL) of subjects with asthma.
      Recently, CX3CR1 (the receptor for CX3CL1) has been proposed as a target for
      airway inflammation, and the paper proposing this was evaluated. The paper
      established a link between CX3CR1 and asthma, as reducing the availability of
      CX3CR1, or inhibiting the responses mediated by the CX3CR1, resulted in reduced
      asthma in a mouse model. This suggests that agents blocking the CX3CR1 may be
      useful in the treatment of asthma. However, there are reports suggesting that
      glucocorticoids may downregulate the CX3CL1-CX3CR1 pathway in inflammation. Thus,
      the next step is to establish whether inhibitors of the CX3CL1-CX3CR1 pathway
      have any additional, or different, effects to glucocorticoids, in the treatment
      of airway inflammatory disorders, in animal models. Subsequently, further
      consideration can be given to the development of CX3CR1 as a target for airway
      inflammation in humans.

PMID- 21714591
TI  - Pulmonary toxicity of well-dispersed multi-wall carbon nanotubes following
      inhalation and intratracheal instillation.
AB  - Multi-walled carbon nanotubes (MWCNTs), dispersed in suspensions consisting
      mainly of individual tubes, were used for intratracheal instillation and
      inhalation studies. Rats intratracheally received a dose of 0.2 mg, or 1 mg of
      MWCNTs and were sacrificed from 3 days to 6 months. MWCNTs induced a pulmonary
      inflammation, as evidenced by a transient neutrophil response in the low-dose
      groups, and presence of small granulomatous lesion and persistent neutrophil
      infiltration in the high-dose groups. In the inhalation study, rats were exposed
      to 0.37 mg/m(3) aerosols of well-dispersed MWCNTs (>70% of MWCNTs were individual
      fibers) for 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after
      the end of exposure. The inhalation exposures delivered less amounts of MWCNTs
      into the lungs, and therefore less pulmonary inflammation responses was observed,
      as compared to intratracheal instillation. The results of our study show that
      well-dispersed MWCNT can produce pulmonary lesions, including inflammation.

PMID- 21714592
TI  - Cyclooxygenase-2 inhibitors: a literature and patent review (2009 - 2010).
AB  - INTRODUCTION: COXs catalyze the complex conversion of arachidonic acid to
      prostaglandins and thromboxanes, which trigger as autacoids with autocrine and
      paracrine biological effects many physiological and pathophysiological responses.
      The structural similarities of the COX-1 and -2 enzymes make the search for
      selective inhibitors for COX-2 versus -1 a formidable challenge. AREAS COVERED:
      The present review provides a survey of the development of novel COX-2 inhibitors
      covering literature and patents between 2009 and 2010. The presence of a central,
      typically 1,2-diaryl substituted, heterocycle or carbocycle as a characteristic
      structural motif in many selective COX-2 inhibitors represents the basis of their
      classification in this review. The classification in this review includes COX-2
      inhibitors based on five- and six-membered heterocycles, benzoheterocycles (e.g.,
      benzopyrans, benzopyranones, indoles and quinolines), quinones, chalcones,
      natural products and miscellaneous. When available, COX-2 inhibitors are
      presented with their related COX-2 inhibitory potency and selectivity. EXPERT
      OPINION: The availability of detailed information on the crystal structure of the
      COX-2 enzyme with various substrates, cofactors and inhibitors, and the recently
      reported increased risk of cardiovascular events associated with selective COX-2
      inhibitors will further stimulate development of COX-2 inhibitors with favorable
      COX-2 inhibition profiles without adverse effects to the cardiovascular system.

PMID- 21714593
TI  - Why is the treatment of hypertension in pregnancy still so difficult?

PMID- 21714594
TI  - Prehypertension and prechronic kidney disease: fact or fiction?

PMID- 21714595
TI  - Heart to heart: challenges and perspectives for genetic research in congenital
      heart disease.

PMID- 21714597
TI  - Renoprotective effects of benazepril: current perspective.
AB  - Cardiovascular (CV) disease, its associated risk factors and continued
      progression run in parallel with renal deterioration (cardio-renal syndrome).
      Most guidelines promote early treatment, including the use of ACE inhibitors to
      control CV risk in patients with chronic renal failure. The renoprotective
      effects of the ACE inhibitor, benazepril, independent of blood pressure control,
      have been demonstrated, as monotherapy or in combination with amlodipine or
      hydrochlorothiazide, in large clinical trials: Avoiding Cardiovascular Events
      through Combination Therapy in Patients Living with Systolic Hypertension
      (ACCOMPLISH) and Gauging Albuminuria Reduction with Lotrel in Diabetic Patients
      with Hypertension (GUARD) in patients with mild-to-severe chronic kidney disease.
      In the ACCOMPLISH trial, CV outcomes and renoprotective effects were greater in
      patients receiving benazepril in combination with amlodipine; the GUARD trial
      demonstrated that combined benazepril/hydrochlorothiazide was more effective than
      amlodipine combined with benazepril in reducing baseline urinary
      albumin:creatinine ratio and normalizing urinary albumin:creatinine ratio in
      patients with baseline microalbuminuria, although this effect was accompanied
      with a greater decrease in glomerular filtration rate than with
      benazepril/amlodipine. While this is not a study in patients with overt renal
      disease (patients had severe CV diseases), the ACCOMPLISH trial is the first
      large study to date to show the added benefit of combining ACE inhibitors and
      calcium-channel blockers in renal protection. Future large, well-controlled
      trials, designed to evaluate hard renal outcomes, are required to identify which
      patients will benefit most from particular combination treatment strategies in
      renoprotection.

PMID- 21714598
TI  - Dronedarone for atrial fibrillation therapy.
AB  - Dronedarone is a new benzofuran derivative that has been developed as an
      antiarrhythmic agent on the basis of the amiodarone molecular structure with the
      intent of maintaining the same pharmacological effects while reducing thyroid and
      pulmonary toxicity. The drug is a multichannel blocker with antiadrenergic
      properties: it reduces heart rate and prolongs the action potential duration.
      Dronedarone is primarily metabolized by cytochrome P450; its half-life is much
      shorter than that of amiodarone because of a lower lipophilicity. As a
      consequence, only 7 days are needed to reach steady-state plasma levels. It has
      been tested in clinical trials both for rate and rhythm control and, even if its
      antiarrhythmic efficacy seems to be somehow lower than that of amiodarone,
      dronedarone is less often discontinued due to adverse reactions or organic
      toxicity. For these reasons, dronedarone can be very useful in long-term
      treatment of atrial fibrillation, by reducing hospitalizations and mortality.

PMID- 21714599
TI  - New clinical concepts after the ONTARGET trial.
AB  - Some aspects of the Ongoing Telmisartan Alone and in Combination with Ramipril
      Global Endpoint Trial (ONTARGET) study are briefly commented on in this article.
      The three main topics of interest related to the study that require further
      analysis are the following: the influence of blood pressure control, and in
      particular, the target blood pressure for patients with established
      cardiovascular disease such as those admitted in the ONTARGET study, the renal
      aspects of the study, which are of great interest but do not adequately clarify,
      in particular, concerns over the dual blockade of the renin-angiotensin
      aldosterone system (RAAS) with telmisartan and ramipril, and finally, and
      probably most importantly, the role of statins in the outcome of the study. A
      high percentage of patients receiving this type of therapy at the end of the
      study, which probably contributed to obtaining a residual risk similar to that in
      the Heart Outcomes Prevention Evaluation (HOPE) study in the absence of treatment
      with RAAS blockers in approximately two-thirds of patients included in the
      ONTARGET trial.

PMID- 21714600
TI  - Angiotensin receptor blockers following acute stroke.
AB  - Elevated blood pressure during the acute stroke period is associated with poor
      neurologic outcomes; however, treating blood pressure in this setting remains
      controversial. Interest in modulating the renin-angiotensin system in this
      setting has gained momentum because of neurohormonal properties, which may
      provide benefits beyond blood pressure control. The Scandinavian Candesartan
      Acute Stroke Trial (SCAST) was recently published describing the effects of
      candesartan in patients with hypertension during the acute stroke period. This
      study shows that lowering blood pressure with an ARB for 7 days poststroke does
      not improve 6-month neurologic outcomes. This article provides a context for a
      continuing discussion regarding the role of blood pressure lowering in patients
      following acute stroke.

PMID- 21714601
TI  - Tackling the thrombotic burden in patients with acute coronary syndrome and
      diabetes mellitus.
AB  - Patients with diabetes mellitus (DM) and coronary artery disease, particularly
      those presenting with acute coronary syndromes (ACS), have a higher risk of
      developing ischemic complications than their nondiabetic counterparts. Although
      ACS patients with DM benefit more than normoglycemic ACS patients from early
      coronary angiography and revascularization, they remain at a higher risk of
      complications following percutaneous coronary intervention and bypass surgery.
      The DM-associated prothrombotic state has been implicated in the pathogenesis of
      these complications and growing data supports the notion that potent platelet
      inhibition is of paramount importance in order to optimize outcomes of DM
      patients presenting with ACS. This article focuses on the evidence supporting the
      concept that augmented platelet reactivity and impaired responsiveness to oral
      antiplatelet agents are influential drivers of the increased propensity of DM
      patients with ACS to develop thrombotic complications. In particular, strategies
      to enhance platelet P2Y(12) receptor inhibition, a key factor to improve outcomes
      in this patient population, are reviewed.

PMID- 21714602
TI  - Myths and truths of growth hormone and testosterone therapy in heart failure.
AB  - Heart failure is a chronic clinical syndrome with very poor prognosis. Despite
      being on optimal medical therapy, many patients still experience debilitating
      symptoms and poor quality of life. In recent years, there has been a great
      interest in anabolic hormone replacement therapy - namely, growth hormone and
      testosterone - as an adjunctive therapy in patients with advanced heart failure.
      It has been observed that low levels of growth hormone and testosterone have been
      associated with increased mortality and morbidity in patients with heart failure.
      Animal studies and clinical trials have shown promising clinical improvement with
      hormonal supplementation. Growth hormone has been shown to increase ventricular
      wall mass, decrease wall stress, increase cardiac contractility, and reduce
      peripheral vascular resistance, all of which might help to enhance cardiac
      function, resulting in improvement in clinical symptoms. Likewise, testosterone
      has been shown to improve hemodynamic parameters via reduction in peripheral
      vascular resistance and increased coronary blood flow through vasodilation,
      thereby improving functional and symptomatic status. To date, growth hormone and
      testosterone therapy have shown some positive benefits, albeit with some concerns
      over adverse effects. However, large randomized controlled trials are still
      needed to assess the long-term safety and efficacy.

PMID- 21714603
TI  - Management of hypertension in diabetic patients: outstanding issues.
AB  - Cardiovascular disease is the leading cause of premature mortality in Type 2
      diabetes mellitus; consequently, good management of all risk factors is vital.
      The recent reappraisal of the European Society of Hypertension guidelines on
      hypertension management reset the blood pressure goal for Type 2 diabetic
      patients to blood pressure <140/90 mmHg. Although this recommendation is based on
      the best available evidence, further data are still required to provide a better
      understanding of the natural history of Type 2 diabetes in order to establish
      blood pressure goals throughout the natural history of the diabetic patient with
      hypertension.

PMID- 21714604
TI  - Recent advances in the treatment of hypertension.
AB  - Uncontrolled blood pressure remains the single most common cause of death
      accounting for more than 7 million deaths per year worldwide. Despite the
      availability of potent lifestyle and pharmacologic approaches, rates of control
      of blood pressure are unsatisfactory and additional strategies to curb the burden
      of hypertension are warranted. Several novel pharmacological- and device-based
      approaches have recently been tested and may prove helpful to achieve better
      blood pressure control rates and thereby improve cardiovascular outcomes in
      patients with hypertension.

PMID- 21714605
TI  - Home blood pressure for the management of hypertension: will it become the new
      standard of practice?
AB  - Accurate identification of hypertension is crucial for the prevention of
      cardiovascular disease. Home blood pressure monitoring (HBPM) provides superior
      prediction of cardiovascular disease, compared with clinic pressures. HBPM can be
      a valuable resource for the effective treatment of hypertension, when combined
      with other modalities used to improve patient education, lifestyle enhancement,
      adherence to medication and reduction of unnecessary clinic visits. In some
      developed nations, more than half of households with a hypertensive patient have
      a device for HBPM. The use of HBPM by patients and the acceptance of HBPM
      measurements by providers is increasing. The long-term effectiveness of HBPM,
      combined with telemetry for disease prevention, is promising. More research is
      still needed to establish its full value. It is predicted that HBPM has definite
      potential for more effective strategies to control hypertension and reduce the
      need for on-site clinical care.

PMID- 21714606
TI  - The role of obesity, salt and exercise on blood pressure in children and
      adolescents.
AB  - The increasing trends of blood pressure (BP) in children and adolescents pose
      great concern for the burden of hypertension-related cardiovascular disease.
      Although primary hypertension in childhood is commonly associated with obesity,
      it seems that other factors, such as dietary sodium and exercise, also influence
      BP levels in children and adolescents. Several studies support that sympathetic
      nervous system imbalance, impairment of the physiological mechanism of pressure
      natriuresis, hyperinsulinemia and early vascular changes are involved in the
      mechanisms causing elevated BP in obese children and adolescents. Under the
      current evidence on the association of salt intake and BP, dietary sodium
      restriction appears to be a rational step in the prevention of hypertension in
      genetically predisposed children and adolescents. Finally, interventional studies
      show that regular aerobic exercise can significantly reduce BP and restore
      vascular changes in obese with hypertensive pediatric patients. This article aims
      to summarize previous studies on the role of obesity, salt intake and exercise on
      BP in children and adolescents.

PMID- 21714607
TI  - Minimally invasive surgical options in pediatric heart surgery.
AB  - Surgery for congenital heart disease has changed considerably during the last
      decade. Improved surgical results in patients with simple congenital heart
      disease and new interventional cardiology procedures have stimulated the surgeon
      to adopt minimally invasive techniques with the aim of reducing the patient's
      surgical insult and obtaining good functional and cosmetic results. As a
      consequence, new surgical techniques and special equipment for minimally invasive
      heart procedures have been developed and refined in recent years. This article
      reports on our institutional protocols for minimally invasive surgery in children
      and adults with congenital heart disease.

PMID- 21714608
TI  - Acute myocarditis in children.
AB  - Myocarditis is an uncommon but significant disease in children. Diagnosis
      requires a high index of suspicion and understanding of the clinical presentation
      of this disease. The understanding of the mechanisms of disease-host immune
      response and host response has improved, but is not completely known. Therapy
      remains mainly supportive, while the use of immunotherapy in children is still
      controversial. The majority of children will improve; however, a substantial
      portion of children will die or develop persistent dilated cardiomyopathy leading
      to necessary heart transplantation.

PMID- 21714609
TI  - The failing Fontan: etiology, diagnosis and management.
AB  - While the Fontan operation has facilitated the survival of a generation of
      children born with congenital heart disease resulting in a functional single
      ventricle, it does not recreate a normal circulation. Over time, survivors of the
      Fontan operation are at risk for ventricular dysfunction, plastic bronchitis,
      protein-losing enteropathy and chronic Fontan failure. New techniques and
      therapies are emerging to address the long-term risks associated with Fontan
      physiology, but as the number of survivors continues to grow, the recognition of
      the limitations of this circulation is increasing. Novel investigations of
      possible mechanical devices designed to function as a subpulmonary ventricle are
      underway, but are still many years away from clinical use. In the meantime,
      continued development of medical therapeutics targeted at the specific problems
      of the Fontan circulation will be beneficial and might reduce the need for
      cardiac transplantation.

PMID- 21714614
TI  - Taxes and entitlements.

PMID- 21714615
TI  - Older men in the homeless shelter: in-depth conversations lead to practice
      implications.
AB  - This article reports on the themes generated by face-to-face interviews conducted
      with 10 men over the age of 50, currently homeless and residing in an overnight
      homeless shelter. In-depth interviews were conducted asking these men to tell
      their stories, talk about their lives in the shelter, and speak about their
      needs, hopes, and dreams. Based on an analysis of interviews, the following
      themes emerged and were presented: Talk of Work, Barriers to Housing are
      Overwhelming, Family Estrangement, and Coping Strategies. Discussion of these
      themes is presented and practice, administrative and research implications are
      suggested.

PMID- 21714616
TI  - A profile of support group use and need among middle-aged and older adults with
      multiple sclerosis.
AB  - This study compared middle-aged and older adults with multiple sclerosis (MS, N =
      1,275) according to their use of support groups and identified factors associated
      with perceived need. Over 64.6% (n = 824) of participants had attended a MS
      support group meeting at least once. Individuals who had never attended a group
      were more likely to reside in urban or suburban communities, report lower symptom
      interference, and fewer activity limitations. Women, individuals without a
      helper, and people with greater symptom interference were more likely to perceive
      a need for a support group. Findings raise questions for professionals involved
      in developing and implementing multiple sclerosis support groups.

PMID- 21714617
TI  - The role of the gerontological social worker in assisted living.
AB  - This qualitative study reports on thirteen assisted living (AL) administrators'
      perspectives of the role and the importance of the AL social worker in addressing
      the unmet needs of older adults as they move and transition into AL. Participant
      interviews were analyzed using the constant comparative method. Administrators
      described 5 AL social work roles: (a) decision-making and adjustment coordinator;
      (b) resident advocate; (c) mental health assessor and counselor; (d) family
      social worker; and (e) care planner. Implications include directly examining AL
      social workers' views, analyzing costs and benefits of employing AL social
      workers, and developing social work practicum sites within AL.

PMID- 21714618
TI  - Exploring the dynamics of middle-aged and older adult residents' perceptions of
      neighborhood safety.
AB  - This study examined what variables best predict concerns about neighborhood
      safety among middle-aged and older adults. Eighty-five participants were selected
      from a Midwestern urban area. Participants completed a 22-item questionnaire that
      assessed their perceptions of neighborhood safety and vigilance. These items were
      clustered as: (a) community care and vigilance, (b) safety concerns, (c) physical
      incivilities, and (d) social incivilities. Police crime data were also used in
      the analyses. Our findings suggest that aspects of the broken window theory,
      collective efficacy, and place attachments play a role in affecting residents'
      perceptions of neighborhood safety.

PMID- 21714619
TI  - It takes a Village: community practice, social work, and aging-in-place.
AB  - The US population of older adults will increase significantly in the coming
      decades. Most of these individuals prefer to age in their homes/communities.
      However, most communities are not prepared to handle the long-term care needs of
      an aging population. This article examines one model that communities are using
      to help older adults age-in-place, the Village. A conceptual lens based in
      community practice and empowerment theory is offered to explicate this model and
      critically evaluate social work's role in it. It also presents challenges to
      social work roles in facilitation and evaluation of the model.

PMID- 21714621
TI  - What is the best measure of psychological reactance? An empirical test of two
      measures.
AB  - This study examines two measures of psychological reactance. In search of
      identifying the best measure, each is compared vis-a-vis the other with respect
      to reliability and validity by placing each in a nomothetic network with a
      freedom threat, attitude, motivation, and source appraisal. The results are
      discussed with an emphasis on future practices regarding the best approach to
      measure psychological reactance.

PMID- 21714622
TI  - Biodegradation of bisphenol-A in river sediment.
AB  - This research investigated the aerobic and anaerobic degradation of bisphenol-A
      (BPA) in river sediment. With the addition of 250 MUg g-1 BPA, the percentages of
      BPA remaining in sediment from sites A, B, and C were 21.9 %, 3.5 % and 12.5 %,
      respectively, after 5 days of incubation under aerobic conditions; degradation
      was not significant after 140 days of incubation under anaerobic conditions. The
      aerobic degradation of BPA was enhanced by adding yeast extract (5 mg L-1),
      sodium chloride (1 %), cellulose (0.96 mg L-1), brij 30 (55 MUM), brij 35 (91
      MUM), rhamnolipid (130 mg L-1), or surfactin (43 mg L-1), with rhamnolipid
      yielding higher BPA degradation than the other additives. 2,4-bis (1,1-dimethyl
      ethyl) phenol, an intermediate product resulting from the aerobic degradation of
      BPA was accumulated in sediments. Of the bacterial strains isolated from the
      sediment, strains J1, J2, J3, and J4 expressed the best aerobic degrading
      ability. The highest BPA degradation rate was found in the sediment by the
      addition of strains J1, J2, J3, and J4 combined, whereas the sediment without the
      addition of the 4 strains had the lowest biodegradation rate. This research
      offers feasible methods for the removal of BPA in river sediment for
      bioremediation.

PMID- 21714623
TI  - Attentional skills 10 years post-paediatric traumatic brain injury (TBI).
AB  - OBJECTIVE: To date no study has reported findings regarding attentional deficits
      following pre-school paediatric traumatic brain injury (TBI), as long as 10 years
      post-injury. It was predicted that more severe TBI would be associated with
      generalized deficits at 10 years post-TBI, particularly for skills not mastered
      at time of injury. RESEARCH DESIGN: The sample comprised 40 prospectively
      recruited children (42% of the original sample) who had sustained a mild,
      moderate or severe traumatic brain injury (TBI) between the ages of 1-7 years and
      19 non-injured control participants. Children were assessed 10 years post-TBI,
      with a focus on measures of attentional ability. OUTCOMES/RESULTS: While
      attentional deficits were not evident across all components of attentional
      ability, both early- and later-established attention skills were compromised,
      particularly following severe TBI. Environmental predictors were generally not
      successful predictors of attentional outcome at 10 years post-TBI. Age at injury
      and acute IQ were identified as contributing to attention at 10 years.
      CONCLUSIONS/IMPLICATIONS: The present study shows that attentional deficits do
      occur and persist to 10 years following serious TBI. Clinicians may be able to
      screen for such deficits and so intervene in order to prevent or lessen the
      consequences of such difficulties.

PMID- 21714624
TI  - Selling the story: narratives and charisma in adults with TBI.
AB  - OBJECTIVE: To examine storytelling performance behaviours in adults with
      traumatic brain injury (TBI) and relate these behaviours to perceived charisma
      and desirability as a conversation partner. DESIGN AND METHODS: Seven adult males
      with traumatic brain injury (TBI) told their accident narratives to a male
      confederate. Ten male undergraduate students rated 1-minute video clips from the
      beginning of each narrative using the Charismatic Leadership Communication Scale
      (CLCS). Raters also indicated whether or not they would like to engage in
      conversation with each participant. RESULTS: Of the performative behaviours
      analysed, gestures alone significantly influenced CLCS ratings and reported
      likelihood of engaging in future conversation with the participant. Post-hoc
      analysis revealed that speech rate was significantly correlated with all of the
      preceding measures. There was a significant correlation between self- and other
      ratings of charisma. CONCLUSIONS: The findings suggest that aspects of non-verbal
      performance, namely gesture use and speech rate, influence how charismatic an
      individual is perceived to be and how likely someone is to engage in conversation
      with that person. Variability in these performance behaviours may contribute to
      the variation in social outcomes seen in the TBI population.

PMID- 21714625
TI  - Salting-out effects on the characterization of naphthenic acids from Athabasca
      oil sands using electrospray ionization.
AB  - There is growing interest in the mass spectrometric characterization of oil sands
      acids present in natural waters and contaminated soils. This interest stems from
      efforts to isolate the principal toxic components of oil sands acid extractable
      organics in aquatic environment. Salting-out effects are demonstrated for
      nanospray ionization mass spectra of Athabasca oil sands acid extractable
      organics (naphthenic acids), using Fourier transform ion cyclotron resonance (FT
      ICR) mass spectrometry. The differences in spectra obtained for the sodium
      naphthenates in dichloromethane/acetonitrile cosolvents compared to spectra
      obtained in the absence of saturated sodium chloride salts, are used here as a
      surrogate to indicate the more bioavailable or toxic components in natural
      waters. Whereas, monocarboxylic compounds (C(n)H(2n+Z)O(2)) were prevalent in the
      Z =-4, -6, and -12 (2, 3 and 6-ring naphthenic acids respectively) family in the
      carbon number range of 13 to 19 in the dichloromethane/acetonitrile cosolvent
      systems, salting-out effects resulted in a general enhancement of Z =-4 species,
      relative to others. Likewise, the shift in relative intensities of species
      containing O(1), O(3), O(4), O(2)S and O(3)S was dramatic for systems with and
      without saturated salts present. The O(4) and O(3)S species for example, were
      prevalent in the dichloromethane/acetonitrile cosolvent but were non-detected in
      the presence of saturated salts. Interactions of oil sands acids with salts are
      expected to occur in oil sands processed waters and natural saline waters. As
      evident by the distribution of species observed, salting-out effects will play a
      major role in limiting the bioavailability of oil sands acids in aquatic systems.

PMID- 21714626
TI  - Analysis of phthalic acid diesters, monoester, and other plasticizers in
      polyvinyl chloride household products in Japan.
AB  - The aim of this study was to determine the concentrations of six phthalic acid
      diesters (PAEs) [di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP),
      butyl benzyl phthalate (BBP), diisononyl phthalate (DINP), di-n-octyl phthalate
      (DNOP), and diisodecyl phthalate (DIDP)], two non-phthalic plasticizers [di(2
      ethylhexyl) adipate (DEHA), 2,2,4-trimethyl-1,3-pentanediol diisobutylate
      (TMPDIB)], and mono 2-ethylhexyl phthalate(MEHP) in polyvinyl chloride (PVC)
      household products that children often places in their mouths and/or contact with
      their skin (41 products, 47 samples) in Japan. The detection frequencies of the
      studied compounds were as follows: DEHP (79 %), DINP-2 (13 %), DINP-1 (11 %), DBP
      (8.5 %), DEHA (8.5 %), DIDP (4.3 %), and DNOP (2.1 %). Concentrations of these
      compounds ranged from 0.021 % to 48 %. BBP and TMPDIB were not detected in the
      all samples. Most samples contained DEHP and DINP at high concentrations over 0.1
      %. High concentrations of PAEs were detected in PVC household products that
      appear appealing to children and can possibly be licked and chewed by them. Di(2
      ethylhexyl) terephtalete, diisononyl 1,2-cyclohexanedicarboxylic acid, acetyl
      tributyl citrate, and di(2-ethylhexyl) 4-cyclohexene-1,2-dicarboxylate used as
      substitute plasticizers were also detected in several samples. MEHP was present
      in 70 % of the samples, with concentrations ranging from trace amounts to 140
      MUg/g. The ratios of MEHP against DEHP were 6.2 * 10(-4) to 1.6 * 10(-1) %. MEHP
      in the household products investigated in this study was most probably an
      impurity in DEHP. The high concentrations of PAEs detected in products that
      children often place in their mouth reveal the importance of replacing
      plasticizers in common household products, and not just children's toys, with
      safer alternatives.

PMID- 21714627
TI  - Repeated measurements for assessment of urinary 2-naphthol levels in individuals
      exposed to polycyclic aromatic hydrocarbons.
AB  - A repeated measurement cohort study was conducted to determine whether 2-napthol
      can be a suitable biomarker for evaluating the magnitude of exposure to PAHs from
      coke oven emissions. Time-course patterns of urinary 2-naphthol levels in coke
      oven workers were examined. Also, the correlation between urinary 2-naphthol
      levels and PAHs from personal breathing zone samples was analyzed while examining
      and adjusting possible confounding factors, such as smoking alcohol consumption,
      and age of human subjects. A total of 8 spot urine samples were collected from
      each high-exposure group (topside-oven workers, n = 17) and low-exposure group
      (side-oven workers, n = 25) during the whole working cycle, which consists of six
      consecutive working days followed by 2 days off. Personal breathing zone samples
      were collected to quantify PAH intake. A questionnaire was distributed and
      collected from each worker for assessment of demographic parameters. Our results
      confirmed that the topside-oven area contained significantly higher PAH levels
      than the side-oven area. Urinary 2-naphthol levels correlated with the levels of
      PAH species, including pyrene, benzo[k]fluoranthene, benezo[g,h,i]pyrene,
      naphthalene, phenanthrene, anthracene, indeno[1,2,3-cd]pyrene,
      benzo[k]fluoranthene, and total PAHs. During the working cycle, urinary 2
      naphthol levels remained stable at around 46-97 ng/mg creatinine during the
      working days and dramatically increased during the off days. After stratification
      of data based on smoking status, smokers had significantly higher urinary 2
      naphthol levels than non-smokers, and 2-naphthol levels positively correlated
      with smoking status. Coke-oven emissions are a source of exposure to naphthalene.
      Also, smoking is a significant source of exposure to naphthalene and served as a
      confounder factor. Due to its abundance, positive association with total PAHs and
      certain carcinogenic PAH compounds, and slower elimination kinetics, urinary 2
      naphthol may have the potential to serve as a biomarker for PAH exposure, when
      smoking status is carefully adjusted.

PMID- 21714628
TI  - Optimization process parameters for in-situ synthesis of ammonia by catalytic
      hydrolysis of urea with fly ash in a batch reactor for safe feedstock in power
      plants.
AB  - In this study, catalytic urea hydrolysis for production of ammonia in presence of
      fly ash, at optimum condition, was investigated in a batch reactor. The single
      and combined effects of operating parameters such as initial feed concentrations,
      temperature, fly ash doses, times and stirring speed on the production of ammonia
      from urea were analyzed using response surface methodology. A 2(5) full factorial
      central composite experimental design was employed. Analysis of variance (ANOVA)
      showed a high coefficient of determination value (R(2)= 0.963) and satisfactory
      prediction second order regression model was derived. The optimum production
      conditions were determined as initial feed concentration 19.9 wt. % of urea,
      temperature 175 degrees C, fly ash dose 7.5 g/L, reaction time 25 min and
      stirring speed 769 rpm. At optimum conversion conditions, the conversion of urea
      for production of ammonia was found to be 99.8 %.

PMID- 21714629
TI  - Kinetics of ozone-initiated oxidation of textile dye, Amaranth in aqueous
      systems.
AB  - The ozone facilitated oxidation mechanism of water soluble azo anionic dye,
      amaranth (Am) was investigated monitoring the depletion kinetics of the dye
      spectrometrically at 521 nm. The oxidation kinetics of the dye by ozone was
      studied under semi-batch conditions, by bubbling ozone enriched oxygen through
      the aqueous reaction mixture of dye, as function of flow rate, ionic strength,
      [O(3)] and pH variations. With excess concentration of ozone and other reagents
      and low [amaranth], reaction followed pseudo-first-order kinetics with respect to
      the dye. Added neutral salts had marginal effect on the reaction rate and the
      variation of pH from 7 to 2 and 7 to 12 exerted only small increases in the
      reaction rate suggesting molecular ozone possibly is the principle reactive
      species in oxidation of dye. The reaction order with respect ozone was near unity
      and it varied slightly with pH and flow rate variations. The overall second-order
      rate constant for the reaction was (105 +/- 4) M(-1) min(-1). The main oxidation
      products immediately after amaranth decolorization were identified. The reaction
      mechanism and overall rate law were proposed. After spiking the seawater, river
      water and wastewaters with Amaranth dye, the reaction rates and trends in BOD and
      COD under control and natural conditions were investigated. The rate of depletion
      of the dye in natural waters was relatively lower, but the ozonation process
      significantly decreased both the BOD and COD levels.

PMID- 21714630
TI  - Influence of diffuse and chronic metal pollution in water and sediments on edible
      seafoods within Ondo oil-polluted coastal region, Nigeria.
AB  - The bioconcentration levels of 3 non-essential elements (Pb, Cd and Ni) have been
      investigated in three different seafoods; Fish (Tilapia zilli), Crab (Callinectes
      sapidus) and periwinkle (Littorina littorea), to investigate the ecosystem health
      status in Ondo oil-polluted coastal region, Nigeria. The seafood samples were
      chosen based on their popularity as a food source and the potential of the
      species to contain high levels of metals based on past research results. Metal
      concentrations in the biota showed marked interspecific differences with C.
      sapidus recording the highest concentrations of all the metals. The
      bioconcentration factor (BCF) showed that C. sapidus and T. zilli have the
      greatest potential to concentrate Cd (BCF = 3-10) and Pb (BCF = 11-84)
      respectively. Lead uptake from both water and sediment (BCF ~ BSAF: 0.003-0.018)
      were abysmally low in L. littorea as compared with other organisms. The high
      concentrations of Pb in fish species, effective bioaccumulation of Cd in species
      of crab and periwinkles, as well as very high BSAF of Ni found in species of crab
      indicated a strong influence from anthropogenic pollutant source on the biotic
      community. Oil pollution appears to be a major source of bioavailable metal
      contaminants for the selected biota. The study shows that C. sapidus and L.
      littorea can effectively compartmentalize potentially toxic metals such as Cd, Pb
      and Ni within their tissues. In terms of toxicity, C. sapidus had Cd
      concentrations greater than the 3,000 ng/g limit set by the Commission of the
      European Communities while Pb concentration exceeded their limits in both C.
      sapidus and T. zilli. All levels of Ni were below the U.S. Food and Drug
      Administration action levels for these metals in fish, crustaceans and shellfish.
      The study revealed anthropogenic enrichment of the metals studied which can
      possibly pose potential threats to the ecology of the area.

PMID- 21714631
TI  - Efficiency of butyl rubber sorbent to remove the PAH toxicity.
AB  - Large amounts of polycyclic aromatic hydrocarbons (PAHs) have been released to
      the marine environment as a result of oil spills and from other sources including
      wastewaters, surface runoff, industrial processes, atmospheric deposition,
      biosynthesis, and natural events such as forest fires. PAHs have been known to
      affect a variety of biological processes and can be potent cell
      mutagens/carcinogens and toxic. In this study, PAH toxicity removal was
      investigated by using a novel macroporous butyl rubber (BR) sorbent. To find out
      the toxicity removal efficiency of the sorbents, the toxicity tests with Vibrio
      fisheri (luminescence bacteria) and Phaeodactylum tricornutum (marine algae) were
      applied to the acenaphthene (Ace) and phenanthrene (Phen) solutions in seawater
      (Ace: 500- 1000 MUg/L; Phen; 100-1000 MUg/L) before and after sorbent
      applications. Additionally, lysosomal stability and filtration rate biomarker
      techniques were applied to the mussels (Mytilus galloprovincialis) exposed to
      1000 MUg/L Phen solution and bioaccumulation was measured. The results showed
      that the toxicity of the PAH solutions decreased 50-100 percent depending on the
      concentration of the solutions and organisms. Phaeodactylum was found as the most
      sensitive organism to Phen and Ace. Since the application of BR sorbent removed
      the Phen from the solution, the bioaccumulated Phen amount in the mussels
      decreased accordingly.

PMID- 21714632
TI  - Influence of soil texture on the electrokinetic transport of diesel-degrading
      microorganisms.
AB  - This work studied the mobilisation of diesel-degrading microorganisms in soils of
      different textures using electrokinetic techniques. The mobilisation tests were
      performed using a laboratory-scale electrokinetic cell in which a synthetic soil
      column was inserted between the cathode and anode compartments. Model soils of
      different textures were prepared by mixing silica and kaolin at different weight
      ratios. Microorganisms were obtained from an undefined diesel-degrading microbial
      culture and located at the anode compartment. In each four hours experiment,
      constant cell voltage was applied, and samples were taken from the cathode
      compartment. Changes in the pH due to water electrolysis were found to
      significantly influence the process performance, and the effect of the carbonate
      concentration (buffer) was studied to clarify this effect. With respect to soil
      texture, it was observed that large particle size led to high numbers of
      microorganisms passing through the soil column, and the presence of small
      particles, which give rise to small pores, was required to improve the retention
      of microorganisms. Finally, current-intensity measurements with different soil
      textures revealed that it was favourable to use only large or small particles,
      whereas a sandy clay soil (50% silica/50% clay) did not favour any of the
      fundamental electrokinetic processes.

PMID- 21714633
TI  - Radon, smoking and lung cancer risk: results of a joint analysis of three
      European case-control studies among uranium miners.
AB  - A combined analysis of three case-control studies nested in three European
      uranium miner cohorts was performed to study the joint effects of radon exposure
      and smoking on lung cancer death risk. Occupational history and exposure data
      were available from the cohorts. Smoking information was reconstructed using self
      administered questionnaires and occupational medical archives. Linear excess
      relative risk models adjusted for smoking were used to estimate the lung cancer
      risk associated with radon exposure. The study includes 1046 lung cancer cases
      and 2492 controls with detailed radon exposure data and smoking status. The
      ERR/WLM adjusted for smoking is equal to 0.008 (95% CI: 0.004-0.014). Time since
      exposure is shown to be a major modifier of the relationship between radon
      exposure and lung cancer risk. Fitting geometric mixture models yielded arguments
      in favor of a sub-multiplicative interaction between radon and smoking. This
      combined study is the largest case-control study to investigate the joint effects
      of radon and smoking on lung cancer risk among miners. The results confirm that
      the lung carcinogenic effect of radon persists even when smoking is adjusted for,
      with arguments in favor of a sub-multiplicative interaction between radon and
      smoking.

PMID- 21714634
TI  - Small molecule cyclin-dependent kinase inhibitors protect against neuronal cell
      death in the ischemic-reperfused rat retina.
AB  - PURPOSE: Recently, cell cycle reentry has been reported in the experimental brain
      ischemia model and Alzheimer's disease brain. Cyclin-dependent kinases (CDKs) are
      known to be key molecules that regulate the cell cycle. The aims of the present
      study were to determine the change in expression of the proteins involved in
      regulation of G1 phase, and to test the effect of small molecule CDK inhibitors
      on neuronal injury in the ischemic-reperfused rat retina. METHODS: Male Sprague
      Dawley rats were anesthetized and subjected to 60 min of retinal ischemia by
      raising intraocular pressure to 130 mmHg. One day after this procedure, the
      retinal tissues were homogenized and immunoblot analyses were done to check the
      expression levels of cell cycle regulatory proteins. Additional groups of rats
      received 3 mg/kg roscovitine, a CDK inhibitor, and 1 mg/kg CDK4 inhibitor
      intravenously (i.v.) 15 min before ischemia and underwent 60 min of ischemia. On
      the 7th day of the retinal ischemia-reperfusion, eyes were subjected to
      morphometry. RESULTS: Immunoblot analysis revealed that ischemia-reperfusion
      significantly increased expression levels of cyclin D1 and CDK4, and decreased
      those of p16(INK4) and p27(KIP1). Treatment with a CDK4 inhibitor (1 mg/kg, i.v.)
      15 min before ischemia significantly reduced death of the retinal ganglion cells.
      CONCLUSION: Upregulation of cell cycle regulatory proteins and activation of
      nonmitotic CDK5 are shown to be associated with neuronal cell death. Although the
      CDK4 inhibitor used in the present study is known to reduce the activity of
      mitotic CDK4, there is no information about its blocking effect on other CDKs,
      such as nonmitotic CDK5. The results in the present study suggest that abnormal
      progression of the cell cycle and/or activation of nonmitotic CDK are involved in
      the neuronal cell death induced by retinal ischemia-reperfusion. Furthermore, as
      shown with a CDK4 inhibitor, agents that alter the activity of CDK may be good
      candidates for inhibitors of neuronal cell death induced by ischemia-reperfusion
      injury.

PMID- 21714635
TI  - Polyoxyethylene hydrogenated castor oil modulates benzalkonium chloride toxicity:
      comparison of acute corneal barrier dysfunction induced by travoprost Z and
      travoprost.
AB  - PURPOSE: To determine the element that modulates benzalkonium chloride (BAC)
      toxicity by using a new electrophysiological method to evaluate acute corneal
      barrier dysfunction induced by travoprost Z with sofZia (Travatan Z((r))),
      travoprost with 0.015% BAC (Travatan((r))), and its additives. METHODS: Corneal
      transepithelial electrical resistance (TER) was measured in live white Japanese
      rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the
      cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z,
      travoprost, and 0.015% BAC. Similarly, TER changes were evaluated after corneas
      were exposed for 60 s to the travoprost additives ethylenediaminetetraacetic acid
      disodium salt, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated
      castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after
      exposure to BAC with or without travoprost additives using scanning electron
      microscopy (SEM) and a cytotoxicity assay. RESULTS: Although no decreases of TER
      were noted after exposure to travoprost Z with sofZia and travoprost with 0.015%
      BAC, a significant decrease of corneal TER was observed after 0.015% BAC
      exposure. With the exception of BAC, no corneal TER decreases were observed for
      any travoprost additives. After corneal exposure to travoprost additives with
      BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations
      and the cytotoxicity assay confirmed that there was a remarkable improvement of
      BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC.
      CONCLUSIONS: Travoprost Z with sofZia and travoprost with BAC do not induce acute
      corneal barrier dysfunction. HCO-40 provides protection against BAC-induced
      corneal toxicity.

PMID- 21714636
TI  - Contamination rates and antimicrobial resistance in Enterococcus spp.,
      Escherichia coli, and Salmonella isolated from "no antibiotics added"-labeled
      chicken products.
AB  - In the United States, products from chickens that were not administered
      antimicrobial medications during growout can contain labels stating "no
      antibiotics added." Here we compared microbial profiles of chicken products
      labeled as coming from birds raised without antimicrobial medications (N=201;
      NON) with chicken products carrying conventional labels (N=201; CONV). There were
      no differences in percentages of samples positive for Enterococcus spp. (CONV:
      17.4%; NON: 21.3%) or Escherichia coli (CONV: 25.9%; NON: 22.3%). The number of
      samples positive for Salmonella was low in both groups, but statistically higher
      in the NON samples (5.0%) versus CONV samples (1.5%; p<0.05). Conversely, CONV
      samples contained higher concentrations of coliforms (CONV: 3.0 log(10)CFU/mL;
      NON: 2.5 log(10)CFU/mL; p<0.05). E. coli (N=190) and Enterococcus spp. isolates
      (N=113) were tested for resistance to common antimicrobials. E. coli isolates
      from CONV samples were more frequently resistant to at least one antimicrobial
      (CONV: 61.3%; NON: 41.2%; p<0.05). Enterococcus spp. isolates from both groups
      were equally likely to be resistant to at least one antimicrobial, but
      Enterococcus spp. isolates from CONV samples were more likely to be resistant to
      erythromycin, kanamycin, and gentamicin (p<0.05). Taken together, these data
      suggest that NON samples may more frequently carry Salmonella; however, E. coli
      and Enterococcus spp. found on CONV are more likely to be resistant to some
      antimicrobials.

PMID- 21714637
TI  - Molecular characterization of Bacillus cereus toxigenic strains isolated from
      different food matrices in Jordan.
AB  - BACKGROUND: Bacillus cereus is increasingly recognized as one of the causative
      agents of food poisoning in different parts of the world. METHODS: In this study,
      molecular characterization of B. cereus toxigenic strains isolated from food in
      Jordan was performed. A total of 202 food samples were collected from local
      markets and restaurants. RESULTS AND DISCUSSION: B. cereus was found in 23.3%
      (47) of the food samples. The hemolytic enterotoxin hblA, hblC, and hblD were
      detected in 40.4%, 36.5%, and 75% of the isolates, respectively. Combination of
      all three hbl genes was detected in 19 isolates (36.5%). The nonhemolytic
      enterotoxin nheA, nheB, and nheC were detected in 61.5%, 92.3%, and 92.3% of the
      isolates, respectively. All three nhe genes were detected in 27 isolates (51.9%).
      The six enterotoxin genes (hemolysin BL [HBL] and NHE complexes) were detected in
      25% of isolates. The cytK gene was detected in 53.8% of B. cereus isolates,
      whereas the bceT gene was detected in 69.2%. Only four emetic toxin-producing
      isolates were found to carry all the three genes of NHE complex, but none of the
      HBL complex ones. The B. cereus Enterotoxin-Reversed Passive Latex Agglutination
      assay results were strongly correlated with molecular detection of the L(2) part
      of the HBL complex (p<=0.01). This study demonstrated the occurrence of
      potentially enterotoxic and emetic toxic B. cereus isolates in the food samples
      analyzed from Jordan.

PMID- 21714638
TI  - Laparoscopic hepatopexy: a new surgical approach to hepatoptosis in an 11-year
      old boy.
AB  - We report a case of hepatoptosis in an 11-year-old boy with a longstanding
      history of intermittent abdominal pain, nausea, and flatulence. The diagnosis of
      hepatoptosis was established by upper gastrointestinal series, abdominal
      ultrasound, and contrast enema so that the working diagnosis of malrotation or
      situs inversus could be excluded. The patient underwent laparoscopic hepatopexy
      with fixation of the ligamentum falciforme hepatis to the right diaphragm and
      fixation of the ligamentum teres hepatis with the distal part of the ligamentum
      falciforme hepatis to the anterior abdominal wall. We describe a new operative
      procedure for hepatoptosis and focus on this rare disease.

PMID- 21714639
TI  - Nutrition support in critical illness--bridging the evidence gap.

PMID- 21714640
TI  - Early versus late parenteral nutrition in critically ill adults.
AB  - BACKGROUND: Controversy exists about the timing of the initiation of parenteral
      nutrition in critically ill adults in whom caloric targets cannot be met by
      enteral nutrition alone. METHODS: In this randomized, multicenter trial, we
      compared early initiation of parenteral nutrition (European guidelines) with late
      initiation (American and Canadian guidelines) in adults in the intensive care
      unit (ICU) to supplement insufficient enteral nutrition. In 2312 patients,
      parenteral nutrition was initiated within 48 hours after ICU admission (early
      initiation group), whereas in 2328 patients, parenteral nutrition was not
      initiated before day 8 (late-initiation group). A protocol for the early
      initiation of enteral nutrition was applied to both groups, and insulin was
      infused to achieve normoglycemia. RESULTS: Patients in the late-initiation group
      had a relative increase of 6.3% in the likelihood of being discharged alive
      earlier from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to
      1.13; P=0.04) and from the hospital (hazard ratio, 1.06; 95% CI, 1.00 to 1.13;
      P=0.04), without evidence of decreased functional status at hospital discharge.
      Rates of death in the ICU and in the hospital and rates of survival at 90 days
      were similar in the two groups. Patients in the late-initiation group, as
      compared with the early-initiation group, had fewer ICU infections (22.8% vs.
      26.2%, P=0.008) and a lower incidence of cholestasis (P<0.001). The late
      initiation group had a relative reduction of 9.7% in the proportion of patients
      requiring more than 2 days of mechanical ventilation (P=0.006), a median
      reduction of 3 days in the duration of renal-replacement therapy (P=0.008), and a
      mean reduction in health care costs of ?1,110 (about $1,600) (P=0.04).
      CONCLUSIONS: Late initiation of parenteral nutrition was associated with faster
      recovery and fewer complications, as compared with early initiation. (Funded by
      the Methusalem program of the Flemish government and others; EPaNIC
      ClinicalTrials.gov number, NCT00512122.).

PMID- 21714642
TI  - Access to safety data--stockholders versus prescribers.

PMID- 21714643
TI  - STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis.
AB  - BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is characterized by
      susceptibility to candida infection of skin, nails, and mucous membranes.
      Patients with recessive CMC and autoimmunity have mutations in the autoimmune
      regulator AIRE. The cause of autosomal dominant CMC is unknown. METHODS: We
      evaluated 14 patients from five families with autosomal dominant CMC. We
      incubated their peripheral-blood mononuclear cells with different combinations of
      stimuli to test the integrity of pathways that mediate immunity, which led to the
      selection of 100 genes that were most likely to contain the genetic defect. We
      used an array-based sequence-capture assay, followed by next-generation
      sequencing, to identify mutations. RESULTS: The mononuclear cells from the
      affected patients were characterized by poor production of interferon-gamma,
      interleukin-17, and interleukin-22, suggesting that the defect lay within the
      interleukin-12 receptor and interleukin-23 receptor signaling pathways. We
      identified heterozygous missense mutations in the DNA sequence encoding the
      coiled-coil (CC) domain of signal transducer and activator of transcription 1
      (STAT1) in the patients. These mutations lead to defective responses in type 1
      and type 17 helper T cells (Th1 and Th17). The interferon-gamma receptor pathway
      was intact in these patients. CONCLUSIONS: Mutations in the CC domain of STAT1
      underlie autosomal dominant CMC and lead to defective Th1 and Th17 responses,
      which may explain the increased susceptibility to fungal infection. (Funded by
      the Netherlands Organization for Scientific Research and others.).

PMID- 21714644
TI  - Better evidence about screening for lung cancer.

PMID- 21714645
TI  - Reduction in intrasubject variability in the pharmacokinetic response to insulin
      after subcutaneous co-administration with recombinant human hyaluronidase in
      healthy volunteers.
AB  - BACKGROUND: This study was designed to test the hypothesis that co-administration
      of recombinant human hyaluronidase (rHuPH20) with regular insulin or insulin
      lispro will reduce intrasubject variability in pharmacokinetic end points
      compared with lispro alone. METHODS: Healthy adult volunteers (18-55 years old)
      were enrolled in this phase 1, randomized, double-blind, crossover study.
      Subjects were administered two injections, each on a separate occasion, of three
      treatments during six euglycemic clamps. Treatments were 0.15 U/kg insulin
      lispro, 0.15 U/kg insulin lispro with 5 MUg/mL rHuPH20, and 0.15 IU/kg regular
      insulin with 5 MUg/mL rHuPH20. Insulin formulations were administered at a
      concentration of 40 U/mL. Serum immunoreactive insulin levels, blood glucose
      concentration, and glucose infusion rate determinations were made at baseline and
      for approximately 8 h after study drug administration. Intrasubject variability
      was assessed using a general linear mixed model with a fixed effect for treatment
      using a compound symmetric covariance matrix. RESULTS: Co-injection of rHuPH20
      with lispro significantly reduced intrasubject root mean square differences in
      time to peak serum insulin, time to early 50% peak serum insulin (t(50%)), and
      time to late t(50%) levels compared with lispro alone. Also, the intrasubject
      coefficient of variation for percentage of total area under the plasma
      concentration-versus-time curve for early time intervals compared with lispro
      alone was reduced. Intrasubject variability for regular insulin with rHuPH20 for
      most pharmacokinetic parameters was similar to the variability of lispro alone,
      although variability in early exposure was significantly reduced. CONCLUSIONS: Co
      administration of rHuPH20 with lispro significantly reduced the variability of
      insulin pharmacokinetics relative to insulin lispro alone.

PMID- 21714646
TI  - Images in clinical medicine. Dependent rubor.

PMID- 21714647
TI  - Assessing the safety of adding LABAs to inhaled corticosteroids for treating
      asthma.

PMID- 21714649
TI  - Antitrypanosomal therapy for chronic Chagas' disease.

PMID- 21714648
TI  - Clinical effect of point mutations in myelodysplastic syndromes.
AB  - BACKGROUND: Myelodysplastic syndromes are clinically heterogeneous disorders
      characterized by clonal hematopoiesis, impaired differentiation, peripheral-blood
      cytopenias, and a risk of progression to acute myeloid leukemia. Somatic
      mutations may influence the clinical phenotype but are not included in current
      prognostic scoring systems. METHODS: We used a combination of genomic approaches,
      including next-generation sequencing and mass spectrometry-based genotyping, to
      identify mutations in samples of bone marrow aspirate from 439 patients with
      myelodysplastic syndromes. We then examined whether the mutation status for each
      gene was associated with clinical variables, including specific cytopenias, the
      proportion of blasts, and overall survival. RESULTS: We identified somatic
      mutations in 18 genes, including two, ETV6 and GNAS, that have not been reported
      to be mutated in patients with myelodysplastic syndromes. A total of 51% of all
      patients had at least one point mutation, including 52% of the patients with
      normal cytogenetics. Mutations in RUNX1, TP53, and NRAS were most strongly
      associated with severe thrombocytopenia (P<0.001 for all comparisons) and an
      increased proportion of bone marrow blasts (P<0.006 for all comparisons). In a
      multivariable Cox regression model, the presence of mutations in five genes
      retained independent prognostic significance: TP53 (hazard ratio for death from
      any cause, 2.48; 95% confidence interval [CI], 1.60 to 3.84), EZH2 (hazard ratio,
      2.13; 95% CI, 1.36 to 3.33), ETV6 (hazard ratio, 2.04; 95% CI, 1.08 to 3.86),
      RUNX1 (hazard ratio, 1.47; 95% CI, 1.01 to 2.15), and ASXL1 (hazard ratio, 1.38;
      95% CI, 1.00 to 1.89). CONCLUSIONS: Somatic point mutations are common in
      myelodysplastic syndromes and are associated with specific clinical features.
      Mutations in TP53, EZH2, ETV6, RUNX1, and ASXL1 are predictors of poor overall
      survival in patients with myelodysplastic syndromes, independently of established
      risk factors. (Funded by the National Institutes of Health and others.).

PMID- 21714650
TI  - Images in clinical medicine. Thrombosis of the inferior vena cava and dilated
      veins of the trunk.

PMID- 21714651
TI  - Case records of the Massachusetts General Hospital. Case 20-2011. A 30-year-old
      man with diarrhea after a trip to the Dominican Republic.

PMID- 21714652
TI  - The dawn of the molecular era of the myelodysplastic syndromes.

PMID- 21714653
TI  - Lessons from sickle cell disease in the treatment and control of malaria.

PMID- 21714654
TI  - Tiotropium versus salmeterol in COPD.

PMID- 21714655
TI  - Tiotropium versus salmeterol in COPD.

PMID- 21714656
TI  - Tiotropium versus salmeterol in COPD.

PMID- 21714657
TI  - Tiotropium versus salmeterol in COPD.

PMID- 21714659
TI  - Prenatal versus postnatal repair of myelomeningocele.

PMID- 21714660
TI  - Prenatal versus postnatal repair of myelomeningocele.

PMID- 21714661
TI  - Prenatal versus postnatal repair of myelomeningocele.

PMID- 21714663
TI  - Anti-IgE for asthma in inner-city children.

PMID- 21714664
TI  - Anti-IgE for asthma in inner-city children.

PMID- 21714641
TI  - Reduced lung-cancer mortality with low-dose computed tomographic screening.
AB  - BACKGROUND: The aggressive and heterogeneous nature of lung cancer has thwarted
      efforts to reduce mortality from this cancer through the use of screening. The
      advent of low-dose helical computed tomography (CT) altered the landscape of lung
      cancer screening, with studies indicating that low-dose CT detects many tumors at
      early stages. The National Lung Screening Trial (NLST) was conducted to determine
      whether screening with low-dose CT could reduce mortality from lung cancer.
      METHODS: From August 2002 through April 2004, we enrolled 53,454 persons at high
      risk for lung cancer at 33 U.S. medical centers. Participants were randomly
      assigned to undergo three annual screenings with either low-dose CT (26,722
      participants) or single-view posteroanterior chest radiography (26,732). Data
      were collected on cases of lung cancer and deaths from lung cancer that occurred
      through December 31, 2009. RESULTS: The rate of adherence to screening was more
      than 90%. The rate of positive screening tests was 24.2% with low-dose CT and
      6.9% with radiography over all three rounds. A total of 96.4% of the positive
      screening results in the low-dose CT group and 94.5% in the radiography group
      were false positive results. The incidence of lung cancer was 645 cases per
      100,000 person-years (1060 cancers) in the low-dose CT group, as compared with
      572 cases per 100,000 person-years (941 cancers) in the radiography group (rate
      ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths
      from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths
      per 100,000 person-years in the radiography group, representing a relative
      reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95%
      CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the
      low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2
      to 13.6; P=0.02). CONCLUSIONS: Screening with the use of low-dose CT reduces
      mortality from lung cancer. (Funded by the National Cancer Institute; National
      Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).

PMID- 21714666
TI  - Adolescent BMI and risk of diabetes versus coronary disease.

PMID- 21714667
TI  - Adolescent BMI and risk of diabetes versus coronary disease.

PMID- 21714669
TI  - Care of transsexual persons.

PMID- 21714671
TI  - Teaching clinicians about drugs.

PMID- 21714673
TI  - Investigation of a researcher's death due to septicemic plague.

PMID- 21714674
TI  - Development and validation of a Spanish diabetes-specific numeracy measure: DNT
      15 Latino.
AB  - BACKGROUND: Although deficits in health literacy and numeracy have been described
      among Latinos, the impact of low numeracy on diabetes outcomes has not been
      studied. Study objectives were (1) to establish the reliability and validity of a
      15-item Spanish, diabetes-specific numeracy measure (Diabetes Numeracy Test [DNT]
      15 Latino) and (2) to examine the relationship between diabetes-specific numeracy
      and diabetes-related outcomes among a sample of Latino adults with diabetes.
      METHODS: Data collection included patient demographics, health literacy, general
      numeracy, diabetes-specific numeracy, acculturation, self-efficacy, self-care
      behaviors, and most recent glycosylated hemoglobin (HbA1c). RESULTS: Participants
      (n=144) were on average 47.8 years old (SD=12.1). The majority were female (62%),
      uninsured (81%), and of Mexican nationality (78%) and reported low levels of
      acculturation (96%). The DNT-15 Latino had high internal reliability (Kruder
      Richardson 20=0.78). The DNT-15 Latino demonstrated construct validity,
      correlating with measures of health literacy (rho=0.291), general numeracy
      (rho=0.500), education (rho=0.361), and income (rho=0.270) (P<0.001 for each).
      The DNT-15 Latino was significantly associated with acculturation but unrelated
      to self-efficacy, self-care behaviors, insulin use, and HbA1c. CONCLUSIONS: The
      DNT-15 Latino is a reliable and valid measure of diabetes-specific numeracy for
      Latino patients with diabetes; however, additional studies are needed to further
      explore the association between diabetes-specific numeracy and acculturation and
      their impact on diabetes-related outcomes for Latinos.

PMID- 21714675
TI  - Continuous subcutaneous insulin infusion (CSII) in inpatient setting: unmet needs
      and the proposal of a CSII unit.
AB  - Continuous subcutaneous insulin infusion (CSII) represents an increasingly
      popular method of treating diabetes. Patients with diabetes are often
      hospitalized, and current data indicate that inpatient hyperglycemia results in
      poorer outcomes. When patients on insulin pump therapy require hospitalization,
      practitioners caring for them face the issue of how to manage the inpatient care
      of these patients. We believe that patients using insulin pumps can safely have
      their therapy transitioned when hospitalized. Moreover, CSII during
      hospitalization should be regarded not only as a fundamental tool in patients
      already on insulin pump therapy, but also as an effective method to obtain
      euglycemia, in critically ill patients. However, a standard policy on CSII use
      during hospitalization is still lacking, and literature data are inconclusive
      about the benefits of insulin pump on glycemic homeostasis, in hospitalized
      patients. We suggest that a CSII unit should be activated inside the hospital, in
      order to increase compliance with required procedures and to properly address the
      unmet needs of CSII in inpatient setting.

PMID- 21714676
TI  - Metabolic clearance rate is a more robust and physiological parameter for insulin
      sensitivity than glucose infusion rate in the isoglycemic glucose clamp
      technique.
AB  - BACKGROUND: The metabolic clearance rate (MCR) of glucose has been defined as the
      value of the glucose infusion rate (GIR) divided by the glucose concentration and
      could be thus expected to be a robust marker at various glucose concentrations.
      METHODS: We evaluated the validity of MCR compared with GIR in 15 healthy
      subjects and 38 type 2 diabetes patients. The glucose clamp technique was
      performed at two different glucose levels-isoglycemia (fasting plasma glucose
      [FPG]) of each subject and euglycemia (100 mg/dL), consecutively. GIR and MCR
      were obtained at both glucose levels, and ratios of those at isoglycemia to
      euglycemia were calculated. RESULTS: Although there was no obvious relationship
      between FPG levels and GIR ratio, the MCR ratio showed a good linear regression
      with FPG levels (r=-0.652, P<0.0001). Furthermore, MCR at FPG was excellently
      (r=0.955) correlated with that at euglycemia in comparison with the modest
      correlation of GIR between the two plasma glucose levels (r=0.876). CONCLUSIONS:
      GIR was rather variable and not proportional to clamped plasma glucose levels.
      MCR was a less variable parameter than GIR at various plasma glucose levels, and
      MCR at FPG in the isoglycemic clamp study could be substituted for GIR at the
      euglycemic clamp study.

PMID- 21714677
TI  - Effect of ambient temperature on analytical performance of self-monitoring blood
      glucose systems.
AB  - BACKGROUND: The analytical quality of self-monitoring of blood glucose (SMBG) can
      be affected by environmental conditions such as temperature. The objective of
      this study was to determine the influence of (1) a shift in the ambient
      temperature immediately before measurement and (2) taking measurements in the
      lower and upper part of the operating temperature range. METHODS: Nine different
      SMBG systems on the Norwegian market were tested with heparinized venous blood
      (4.8 and 19.0 mmol/L). To test the shift in ambient temperature effect, the
      glucometer and strips were equilibrated for 1 h at 5 degrees C or 1 h at 30
      degrees C before the meter and strips were moved to room temperature, and
      measurements were performed after 0, 5, 10, 15, and 30 min. To test the lower and
      upper temperature range, measurements were performed at 10 degrees C and at 39
      degrees C after 1 h for temperature equilibration of the glucometer and strips.
      All these measurements were compared with measurements performed simultaneously
      on a meter and strips kept at room temperature the whole time. RESULTS: Six of
      nine SMBG systems overestimated and/or underestimated the results by more than 5%
      after moving meters and strips from 5 degrees C or 30 degrees C to room
      temperature immediately before the measurements. Two systems underestimated the
      results at 10 degrees C. One system overestimated and another underestimated the
      results by more than 5% at 39 degrees C. CONCLUSIONS: The effect on analytical
      performance was most pronounced after a rapid shift in the ambient temperature.
      Therefore patients need to wait at least 15 min for temperature equilibration of
      affected meters and strips before measuring blood glucose.

PMID- 21714678
TI  - A new tool to detect kidney disease in Chinese type 2 diabetes patients:
      comparison of EZSCAN with standard screening methods.
AB  - BACKGROUND: EZSCAN((r)) (Impeto Medical, Paris, France), a noninvasive device
      that assesses sweat gland dysfunction using reverse iontophoresis, also detects
      early dysglycemia. Given the interrelationships among dysglycemia, vasculopathy,
      and neuropathy, EZSCAN may detect kidney disease in diabetes (DKD). METHODS: An
      EZSCAN score (0-100) was calculated using a proprietary algorithm based on the
      chronoamperometry analysis. We measured the score in 50 Chinese type 2 diabetes
      patients without DKD (urinary albumin-creatinine ratio [ACR] <2.5 mg/mmol in men
      or ACR <3.5 mg/mmol in women and estimated glomerular filtration rate [eGFR] >90
      mL/min/1.73 m(2)) and 50 with DKD (ACR >=25 mg/mmol and eGFR <60 mL/min/1.73
      m(2)). We used spline analysis to determine the threshold value of the score in
      detecting DKD and its sensitivity and specificity. RESULTS: EZSCAN scores were
      highly correlated with log values of eGFR (r=0.67, P<0.0001) and ACR (r=-0.66,
      P<0.0001). Using a cutoff value of 55, the score had 94% sensitivity, 78%
      specificity, and a likelihood ratio of 4.2 to detect DKD with a positive
      predictive value of 81% and a negative predictive value of 93%. On multivariable
      analysis, DKD was independently associated with EZSCAN score (beta=-0.72,
      P=0.02), smoking status (1=never, 0=current/former) (beta=-2.37, P=0.02),
      retinopathy (1=yes, 0=no) (beta=3.019, P=0.01), triglycerides (beta=2.56,
      P=0.013), and blood hemoglobin (beta=-0.613, P=0.04). Patients without DKD but
      low EZSCAN score (n=10) had longer duration of disease (median [interquartile
      range], 13 [9-17] vs. 8 [4-16] years; P=0.017) and were more likely to have
      retinopathy (36.7% vs. 5.1%, P=0.02), lower eGFR (98 [95.00-103] vs. 106 [98.5
      115], P=0.036), and treatment with renin-angiotensin system blockers (81.8% vs.
      25.6%, P=0.002) than those with a normal score. CONCLUSION: EZSCAN may detect
      high-risk subjects for DKD in Chinese populations.

PMID- 21714679
TI  - Glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus
      using lispro versus regular insulin: a systematic review and meta-analysis.
AB  - AIMS: This study performed a systematic review and meta-analysis on glycemic
      control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM)
      treated with lispro (LP) versus regular insulin (RI) since before pregnancy.
      METHODS: We performed a MEDLINE and EMBASE search. Abstracts (and full articles
      when appropriate) were reviewed by two independent researchers. Inclusion
      criteria were patients with T1DM, data on women treated with RI and LP since
      before pregnancy until delivery in the same article, at least five pregnancies in
      each group, and information on at least one pregnancy outcome. Quality assessment
      was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort
      studies. RESULTS: Outcome data were summarized with Revman version 5.0
      (ims.cochrane.org/revman/download [The Nordic Cochrane Centre, The Cochrane
      Collaboration, Copenhagen, Denmark]), applying a random effects model. Two
      hundred sixty-seven abstracts were identified, and four full articles fulfilled
      inclusion criteria, all of them corresponding to observational studies. Baseline
      characteristics were similar in women treated with LP or RI. Regarding outcome
      data, no differences between LP and RI groups were observed in hemoglobin A1c,
      gestational age at birth, birth weight, and rate of diabetic ketoacidosis,
      pregnancy-induced hypertension, pre-eclampsia, spontaneous miscarriages,
      interruptions, total abortions, cesarean section, preterm birth, macrosomia,
      small-for gestational-age newborns, stillbirth, neonatal and perinatal mortality,
      neonatal hypoglycemia, and major malformations. The rate of large-for-gestational
      age newborns was higher in the LP group (relative risk 1.38; 95% confidence
      interval 1.14-1.68). CONCLUSIONS: In relation to women with T1DM treated with RI,
      those treated with LP display similar baseline characteristics and no differences
      in metabolic control or perinatal outcome with the exception of a higher rate of
      large-for-gestational-age newborns.

PMID- 21714680
TI  - Effects of sleep apnea severity on glycemic control in patients with type 2
      diabetes prior to continuous positive airway pressure treatment.
AB  - BACKGROUND: Obstructive sleep apnea (OSA), a highly prevalent condition, is
      independently associated with increased risks of developing type 2 diabetes
      mellitus (T2D) and metabolic syndrome. It is unclear, however, if the severity of
      OSA has any impact on glycemic control among patients with T2D. We therefore
      aimed to determine the independent association between OSA severity and
      glycosylated hemoglobin (HbA1c) in patients with T2D. METHODS: This was an
      observational cross-sectional study of 52 consecutive patients attending the
      diabetes obesity clinic between January 2008 to February 2010 with risk factors
      for sleep apnea and who underwent polysomnography study. Clinical, demographic,
      and lifestyle data were recorded using a questionnaire. RESULTS: Prevalence of
      OSA in this clinical cohort was 58%. After adjusting for age, gender, body mass
      index, duration of diabetes, and insulin dose, increased severity of OSA was
      associated with increased HbA1c levels (P<0.014 for linear trend). A plateau
      effect between HbA1c and OSA severity was, however, noted from moderate to severe
      OSA levels. The adjusted mean values of HbA1c in each OSA category were 8.62% for
      none, 9.36% for mild, 10.61% for moderate, and 9.91% for severe. No significant
      associations were noted between liver transaminase level with OSA severity
      (P=0.324), between body mass index with OSA severity (P=0.278), or between HbA1c
      levels with the Epworth Score (a measure of daytime sleepiness) (P=0.46).
      CONCLUSIONS: Increased severity of OSA is independently associated with worsening
      glycemic control following adjustment of various confounders, including insulin
      dosage. We would hypothesize therefore that identification and treating OSA among
      patients with T2D may confer benefits in improving glycemic control.

PMID- 21714681
TI  - Normal reference range for mean tissue glucose and glycemic variability derived
      from continuous glucose monitoring for subjects without diabetes in different
      ethnic groups.
AB  - BACKGROUND: Glycemic variability has been proposed as a contributing factor in
      the development of diabetes complications. Multiple measures exist to calculate
      the magnitude of glycemic variability, but normative ranges for subjects without
      diabetes have not been described. For treatment targets and clinical research we
      present normative ranges for published measures of glycemic variability. METHODS:
      Seventy-eight subjects without diabetes having a fasting plasma glucose of <120
      mg/dL (6.7 mmol/L) underwent up to 72 h of continuous glucose monitoring (CGM)
      with a Medtronic Minimed (Northridge, CA) CGMS((r)) Gold device. Glycemic
      variability was calculated using EasyGV((c)) software (available free for non
      commercial use at www.easygv.co.uk ), a custom program that calculates the SD, M
      value, mean amplitude of glycemic excursions (MAGE), average daily risk ratio
      (ADRR), Lability Index (LI), J-Index, Low Blood Glucose Index (LBGI), High Blood
      Glucose Index (HBGI), continuous overlapping net glycemic action (CONGA), mean of
      daily differences (MODD), Glycemic Risk Assessment in Diabetes Equation (GRADE),
      and mean absolute glucose (MAG). RESULTS: Eight CGM traces were excluded because
      there were inadequate data. From the remaining 70 traces, normative reference
      ranges (mean+/-2 SD) for glycemic variability were calculated: SD, 0-3.0; CONGA,
      3.6-5.5; LI, 0.0-4.7; J-Index, 4.7-23.6; LBGI, 0.0-6.9; HBGI, 0.0-7.7; GRADE, 0.0
      4.7; MODD, 0.0-3.5; MAGE-CGM, 0.0-2.8; ADDR, 0.0-8.7; M-value, 0.0-12.5; and MAG,
      0.5-2.2. CONCLUSIONS: We present normative ranges for measures of glycemic
      variability in adult subjects without diabetes for use in clinical care and
      academic research.

PMID- 21714682
TI  - Addressing schemes of self-monitoring of blood glucose in type 2 diabetes: a
      European perspective and expert recommendation.
AB  - Self-monitoring of blood glucose (SMBG) in type 2 diabetes has increasingly been
      shown to display beneficial effects on glycemic control. SMBG is not only
      associated with a reduction of hemoglobin A1c but has also been demonstrated to
      increase patients' awareness of the disease. SMBG has also the potential to
      visualize and predict hypoglycemic episodes. International guidelines by the
      International Diabetes Federation, the European Society of Cardiology, and the
      European Association for the Study of Diabetes and also the International Society
      for Pediatric and Adolescent Diabetes emphasize that SMBG is an integral part of
      self-management. More recently, two European consensus documents have been
      published to give recommendations for frequency and timing of SMBG also for
      various clinical scenarios. Recently, a European expert panel was held to further
      facilitate and enhance standardized approaches to SMBG. The aim was to present
      simple, clinically meaningful, and standardized SMBG strategies for type 2
      diabetes. The panel recommended a less intensive and an intensive scheme for SMBG
      across the type 2 diabetes continuum. The length and frequency of SMBG
      performance depend on the clinical circumstances and the quality of glycemic
      control. The expert panel also recommended further evaluation of various schemes
      for SMBG in type 2 diabetes in clinical studies.

PMID- 21714683
TI  - Appropriate values of adiposity and lean body mass indices to detect
      cardiovascular risk factors in Asian Indians.
AB  - OBJECTIVES: The objective of this study was to determine the gender-specific
      appropriate values of direct measurements of adiposity and lean body mass in
      Asian Indians. METHODS: Data was collected cross-sectionally in 168 healthy urban
      Asian Indian individuals. Dual-energy X-ray absorptiometry and anthropometry were
      used to measure various body composition and fat distribution parameters. Blood
      pressure, serum lipids, fasting blood glucose, and 2-h glucose in an oral glucose
      tolerance test were used to identify the cardiovascular risk factors. Subjects
      were classified according to the presence of two or more of these cardiovascular
      risk factors. RESULTS: Appropriate cutoff values for total body fat (%), fat mass
      (kg), total lean mass (%), lean mass (kg), and fat free mass (kg) were 25.5,
      15.1, 73.7, 46.3, and 48.8 for males and 38.0, 20.3, 59.0, 32.6, and 34.8 for
      females. Corresponding values for fat arm (%), fat mass arm (kg), fat leg (%),
      fat mass leg (kg), fat trunk (%), and fat mass trunk (kg) were 19.8, 1.4, 21.9,
      4.1, 30.1, and 8.8 for males and 43.3, 3.1, 38.9, 6.9, 38.5, and 9.5 for females.
      Stepwise logistic regression analysis confirmed the relatively strong and
      independent association of fat mass trunk in men and fat mass arm in women with
      the clustering of cardiovascular risk factors. CONCLUSIONS: Gender-specific
      cutoffs of direct indices of adiposity and lean body mass are presented in this
      article, which could be used for clinical and research purpose to detect
      cardiovascular risk and for categorizing obesity and truncal adiposity in urban
      Asian Indians.

PMID- 21714684
TI  - Alcohol consumption and risk of lung cancer in the VITamins And Lifestyle Study.
AB  - The effect of alcoholic beverage consumption on lung cancer risk was investigated
      in the VITamins And Lifestyle (VITAL) Study. The VITAL study is a prospective
      cohort of residents aged 50-76 yr in Washington state. Five hundred and eighty
      incident lung cancer cases diagnosed between study baseline (2000-2002) and 2007
      were identified among 66,186 participants without previous cancer through the
      Washington Surveillance Epidemiology and End Result cancer registry.
      Multivariable Cox's regression was used to examine the effects of beer, red wine,
      white wine, liquor, combined alcoholic beverage intake at study baseline, and
      alcohol intake at age 30 and 45 on lung cancer risk, with careful adjustment for
      smoking. There was no clear association between lung cancer and consumption of
      beer, red wine, white wine, or liquor at >=1 drink/day. Combined alcoholic
      beverage intake of up to >=3 drink/day was not associated with elevated overall
      lung cancer risk. Heavy consumption of alcohol at study baseline and at age 45
      was, however, associated with more than doubling of risk for squamous cell
      carcinoma (hazard ratio for >=3 drink/day at study baseline = 2.54, 95% CI: 1.36
      4.73, P value for linear trend = 0.002) but not for adenocarcinoma. Alcohol
      intake at age 30 was not associated with lung cancer risk.

PMID- 21714685
TI  - Dietary glycemic load, glycemic index, and carbohydrate and risk of breast cancer
      in the Women's Health Initiative.
AB  - Dietary glycemic load (GL), glycemic index (GI), and carbohydrate could be
      associated with breast cancer risk by influencing long-term blood glucose and
      insulin concentrations. We examined associations between GL, GI, and carbohydrate
      and incident breast cancer in 148,767 Women's Heath Initiative (WHI)
      participants. Dietary variables were estimated from food frequency questionnaires
      administered at baseline. Self-reported breast cancers during follow-up were
      confirmed by medical records review. Cox proportional hazards regression modeled
      time to breast cancer within quintiles of GL, GI, and carbohydrate. There were
      6,115 total breast cancers after a median follow-up of 8.0 yr. We observed no
      associations between GL, GI, or carbohydrate and total incident breast cancer,
      with hazard ratios and 95% confidence intervals for the highest vs. lowest
      quintiles of 1.08, 0.92-1.29 (P for trend = 0.27); 1.01, 0.91-1.12 (P = 0.74);
      and 0.95, 0.80-1.14 (P = 0.98), respectively. There was a trend toward
      significance for the positive association between GL and in situ cancers (1.40,
      0.94-2.13; P = 0.07). Although there was no evidence of associations between GL,
      GI, or carbohydrate and total breast cancer risk in WHI participants, the
      suggestion of an association between GL and risk of in situ cancers requires
      further investigation.

PMID- 21714686
TI  - Efficacy and safety of short-term genistein intervention in patients with
      localized prostate cancer prior to radical prostatectomy: a randomized, placebo
      controlled, double-blind Phase 2 clinical trial.
AB  - We conducted a placebo-controlled, block-randomized double-blind Phase 2 study to
      examine the effect of 30 mg synthetic genistein daily on serum and tissue
      biomarkers in patients with localized prostate cancer (CaP). Fifty-four study
      subjects were recruited and randomized to treatment with genistein (n = 23) or
      placebo (n = 24) for 3 to 6 wk prior to prostatectomy. Seven study subjects were
      noncompliant to the study protocol. Adverse events were few and mild. Serum
      prostate specific antigen (PSA) decreased by 7.8% in the genistein arm and
      increased by 4.4% in the placebo arm (P = 0.051). The PSA level was reduced in
      tumor tissue compared to normal tissue in the placebo arm. In the genistein arm,
      the PSA level in tumor and normal tissue was comparable. Total cholesterol was
      significantly lower in the genistein arm (P = 0.013). There were no significant
      effects on thyroid or sex hormones. Plasma concentrations of total genistein were
      on average 100-fold higher in the genistein arm after treatment (P < 0.001).
      Genistein at a dose that can be easily obtained from a diet rich in soy reduced
      the level of serum PSA in patients with localized CaP, without any effects on
      hormones. It was well tolerated and had a beneficial effect on blood cholesterol.

PMID- 21714687
TI  - Weight loss during radiotherapy for nasopharyngeal carcinoma: a prospective study
      from northern China.
AB  - The objective of this explorative study was to measure weight loss during
      radiotherapy and to select predictive factors for early identification of
      malnourished patients. One hundred and fifty-nine consecutive initial diagnosed
      nasopharyngeal carcinoma patients attending the Oncology Center at Qilu Hospital
      of Shandong University, China participated. Patients' weights were measured at
      the baseline visit and at the end of radiotherapy. The baseline characteristics
      were recorded. A stepwise linear regression analysis was performed to find
      association between baseline characteristics and malnutrition. At baseline, 56%
      of the patients already had a 5% weight loss during the last 3 mo; after the
      treatment, the median weight loss was 6.9 kg (range, 2.1-12.6 kg). After the
      multivariate linear regression analyses, the following factors turned out to be
      independent prognostic factors for significant weight loss: global quality of
      life, body mass index, N stage, insomnia, radiation techniques, Karnofsky
      performance status, concurrent chemotherapy, and fatigue. The authors conclude
      that severe weight loss during radiotherapy for nasopharyngeal carcinoma is
      common. A combination of clinical factors may lead to malnutrition for
      nasopharyngeal carcinoma during radiotherapy.

PMID- 21714688
TI  - Risk factors of dementia in North India: a case-control study.
AB  - OBJECTIVE: The prevalence of dementia in northern India is among the lowest in
      the world but reasons are unclear. The aim of the study was to evaluate the risk
      and protective factors for dementia in North India. METHODS: In a case-control
      study, we investigated demographic, medical, genetic, dietary, lifestyle, and
      sociocultural protective and risk factors associated with dementia. RESULTS: 150
      patients of dementia (118 males and 32 females) and 150 healthy controls (112
      males and 38 females) were included in the study. Diabetes, depression,
      hyperhomocysteinemia, hyperlipidemia, APOE epsilon4 gene, BMI, use of saturated
      fatty acids, pickles in diet, urban living, and lack of exercise were associated
      with independent risk of dementia. Various dietary factors and sociocultural
      factors, like cognitively stimulating activities, active socialization, living in
      joint families, increased intake of polyunsaturated fats, fruits, and salads
      conferred protection against dementia. CONCLUSIONS: Dietary, lifestyle, and
      sociocultural interventions may be protective against dementia.

PMID- 21714689
TI  - Development and implementation of collaborative care for depression in HIV
      clinics.
AB  - We sought to develop and implement collaborative depression care in human
      immunodeficiency virus (HIV) clinics in a project called HIV Translating
      Initiatives for Depression into Effective Solutions (HITIDES). Here we describe:
      (i) the formative evaluation (FE) conducted prior to implementation; (ii) the
      process used to adapt the primary care collaborative care model for depression to
      specialty HIV clinics; and (iii) the intervention itself. The overall design of
      HITIDES was a multi-site randomized trial in United States Department of Veterans
      Affairs (VA) HIV clinics comparing the depression collaborative care intervention
      to usual depression care. Qualitative methods were used for the FEs and informed
      the evidence-based quality improvement (EBQI) methods that were used for adapting
      and implementing the intervention. Baseline assessments were completed by 249
      depressed HIV participants. Summaries of respective key informant interviews with
      eight HIV patients who were receiving depression treatment and 25 HIV or mental
      health (MH) providers were presented to each site. EBQI methods were used to
      tailor the HITIDES intervention to each site while maintaining true to the
      evidence base for depression collaborative care. EBQI methods provided a useful
      framework for intervention adaptation and implementation. The HITIDES study
      provides the opportunity to evaluate collaborative depression care in a specialty
      physical health clinic setting with a population that has a high prevalence of
      depression and MH comorbidity.

PMID- 21714690
TI  - Psychosocial factors associated with sexual behaviour in early adolescence.
AB  - OBJECTIVES: To compare the psychosocial characteristics of sexually inexperienced
      adolescents with those of youths who had had sex, whether safe or unsafe.
      METHODS: We gathered information on self-esteem, well-being, social support,
      family structure, educational aspiration, parental education and sexual behaviour
      of 2318 adolescents (mean-age 14.3 years) attending elementary school in
      Slovakia. Those who reported having had first sex after a relationship shorter
      than one month, who reported sex after alcohol consumption, who had had four or
      more sexual partners or who inconsistently used a condom were considered to have
      engaged in unsafe sex. RESULTS: Respondents who were younger, female, reported
      living in an intact family or having a higher level of social support from family
      were more likely to still be virgins. Adolescents who had sex, whether safe or
      unsafe, had similar psychosocial characteristics. Those who reported a higher
      level of positive self-esteem or social support from friends, but a lower level
      of well-being, social support from family or educational aspiration were more
      likely to engage in unsafe sex. CONCLUSION: Psychosocial features of adolescents
      who reported having had unsafe sex were similar to those of adolescents who had
      had safe sex but differed from the characteristics of adolescents who reported
      not to have started sexual activity.

PMID- 21714691
TI  - Intrapartum antibiotic prophylaxis failure and group-B streptococcus early-onset
      disease.
AB  - OBJECTIVES: To determine factors influencing intrapartum antibiotic prophylaxis
      (IAP) failure in the prevention of group B streptococcus (GBS) early-onset
      disease (EOD). METHODS: GBS EOD case is defined as isolation of GBS from a
      normally sterile body site (e.g. blood or cerebrospinal fluid) in infants aged
      <=7 days. During a consecutive 93-month period, GBS EOD cases and care data were
      reviewed. RESULTS: Seventy-nine GBS EOD cases were registered; 67 infants were
      born to women who received no i.v. antibiotics during labor. The 12 EOD cases
      exposed to IAP were more likely to be associated with emergency caesarean section
      (p = 0.0015), maternal obstetric risk factors (ORFs) (p = 0.0061), particularly
      intrapartum fever (p = 0.0002), and to present with signs of illness at birth (p
      = 0.0015). Correct dosages, agents, and timing were registered in three cases
      only; of which two were associated with intrapartum fever. CONCLUSIONS: ORFs,
      emergency caesarean section, and signs of illness at birth are significantly
      associated with GBS EOD in infants exposed to IAP. This study also suggests that
      recommended IAP agents, dosages, and timing are infrequently associated with EOD.
      Strict protocol adherence is recommended in all cases.

PMID- 21714692
TI  - Managing the difficult case of fetal anemia.
AB  - OBJECTIVES: To describe a series of complex fetal anemia cases, detail the
      appropriate investigations and management, and review the literature. METHODS:
      Four cases of non-red cell alloimmunization or infective cases of fetal anemia
      are presented. RESULTS: Of the four cases presented, one was a neonatal death,
      one pregnancy was terminated, one case was diagnosed with Diamond Blackfan
      anemia, and one case was due to recurrent feto-maternal hemorrhages despite
      negative Kleihauer tests. CONCLUSIONS: Non-alloimmune causes of fetal anemia can
      be difficult to manage. Some cases require repeated and frequent intrauterine
      transfusions. The perinatal mortality and preterm delivery rates are increased,
      and some cases require considerable long-term treatment including regular
      transfusions. We present our experience of a series of non-immune fetal anemia
      managed in a tertiary unit, review the literature, and suggest appropriate
      management.

PMID- 21714693
TI  - Low-dose vaginal misoprostol in the management of intrauterine fetal death.
AB  - OBJECTIVES: To assess the effectiveness and side effects of vaginal misoprostol
      (Vagiprost(r) tablet) termination of second and third trimester pregnancy
      complicated with intrauterine fetal death (IUFD). DESIGN: A prospective
      observational cohort study. SETTING: Tanta University Hospital. Patients. The
      study carried out on 324 women with fetal demise in the second and third
      trimesters, from January 2008 to December 2009. INTERVENTION: All patients were
      subjected to history taking, physical examination, and the Bishop Scoring.
      Application of 25 MUg misoprostol in the posterior fornix of the vagina, this was
      repeated every 4 h over 24 h. We assessed the adverse effects, progress, and
      outcomes. RESULTS: The success rate was 90% and 45% in women in the third and
      second trimesters, respectively. The mean induction-termination interval was 8.95
      +/- 2.63 and 15.3 +/- 5.37 h for women in the third and second trimesters,
      respectively. The induction termination interval correlated negatively with the
      duration of gestation. Approximately, 90% of second trimester and 55% of third
      trimester women required oxytocin augmentation. The mean value of total required
      dose of misoprostol was 166.3 +/- 7.5 and 120 +/- 28.79 MUg for women in the
      second and third trimesters, respectively. CONCLUSION: Vagiprost appears to be a
      safe, effective, practical, and inexpensive method for termination of third
      trimester pregnancy complicated with of IUFD.

PMID- 21714694
TI  - Placental abruption, offspring sex, and birth outcomes in a large cohort of
      mothers.
AB  - OBJECTIVE: To investigate stillbirth, neonatal, and perinatal death outcomes in
      pregnancies complicated by placental abruption, according to fetal sex. METHODS:
      We utilized maternally linked cohort data files of singleton live births to
      mothers diagnosed with placental abruption during the period 1989 through 2005 (n
      = 10,014). Logistic regression models were employed to generate adjusted odd
      ratios and their 95% confidence intervals. Male babies served as the referent
      category. RESULTS: The sex ratio at birth was 1.18. The overall prevalence of
      stillbirth, neonatal mortality, and perinatal mortality was 7.2%, 4.5%, and
      11.8%, respectively. Placental abruption was less likely to occur in mothers
      carrying female pregnancies than mothers of male infants (adjusted odds ratio
      [95% confidence interval] = 0.89 [0.86-0.93]). There were no significant sex
      differences with regards to stillbirth, neonatal mortality, and perinatal
      mortality. Similar findings were observed for preterm and term infants.
      CONCLUSIONS: Although a preponderance of male infants was discernable among
      mothers with placental abruption, no sex difference in fetal survival was
      observed among the offspring of the mothers affected by placental abruption.

PMID- 21714695
TI  - Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm
      injection outcome.
AB  - OBJECTIVE: The purpose of this study was to evaluate the association between the
      follicular fluid (FF) reactive oxygen species (ROS) levels, total antioxidant
      capacity (TAC) and ROS-TAC score and pregnancy after intracytoplasmic sperm
      injection (ICSI). METHODS: A total of 138 consecutive women who had ICSI were
      included in this study. FF ROS and TAC were measured by enhanced
      chemiluminescence and colorimetric assay, respectively, and then the ROS-TAC
      score was calculated. RESULTS: Out of the 138 included patients, 42 (30%)
      achieved pregnancy after ICSI. Log ROS, TAC, and the ROS-TAC score were not
      significantly different across diagnoses. Pregnant cycles were associated with
      significantly lower ROS (P < 0.001), higher TAC (P < 0.001) and higher ROS-TAC
      scores (P < 0.001). After adjusting for age, there was a significant positive
      correlation between log ROS and the number of follicles on the day of HCG
      administration (correlation 0.20, 95% CI: 0.02, 0.39) as well as the number of
      oocytes retrieved (correlation 0.18, 0.001, 0.36) but not with TAC.
      Interestingly, in women with endometriosis, higher TAC levels and higher ROS-TAC
      scores were associated with a higher likelihood of finding normal oocytes (P =
      0.005 and P = 0.002, respectively). CONCLUSION: Higher FF TAC, higher FF ROS-TAC
      scores and lower FF ROS levels are associated with pregnancy after ICSI.
      Oxidative stress parameters may be markers of metabolic activity within the
      follicle.

PMID- 21714696
TI  - Insulin sensitivity in late gestation and early postpartum period: the role of
      circulating maternal adipokines.
AB  - OBJECTIVE: Early postpartum period is characterised by a dramatic decrease in
      insulin resistance and significant metabolic alterations. The aims of this study
      were to determine the changes in circulating maternal concentrations of total
      adiponectin, adiponectin multimers, leptin and resistin before and after the
      delivery and to explore their relationship with insulin sensitivity. METHODS:
      Twenty-seven normal pregnant women at term were included in this longitudinal
      study. Blood samples were taken before and 4 days after elective caesarean
      section. Total adiponectin, adiponectin multimers, leptin, resistin, glucose,
      insulin and prolactin were measured in maternal serum. Adiponectin multimers were
      measured before and after the delivery in eight women. RESULTS: (1) The mean
      maternal serum total adiponectin concentration was significantly higher before
      than after delivery while the relative distribution of circulating maternal
      adiponectin multimers did not change after delivery; (2) the median maternal
      serum concentration of leptin was significantly higher in the antepartum than in
      the postpartum period; (3) the median maternal serum resistin concentration was
      comparable before and after delivery; (4) multiple linear regression analysis
      revealed that antepartum insulin sensitivity was associated with maternal low
      body mass index, and low glucose concentrations in glucose challenge test, as
      well as with maternal age and increased leptin concentrations. Postpartum insulin
      sensitivity was associated with decreased circulating resistin concentrations.
      CONCLUSIONS: Despite increase in insulin sensitivity, early postpartum period is
      characterised by a decrease in maternal circulating total adiponectin and by
      steady concentrations of resistin and adiponectin multimers compared to the late
      third trimester.

PMID- 21714697
TI  - Extended high dose letrozole regimen versus short low dose letrozole regimen as
      an adjuvant to gonadotropin releasing hormone antagonist protocol in poor
      responders undergoing IVF-ET.
AB  - OBJECTIVE: To compare the efficacy and cost-effectiveness of extended high dose
      letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant)
      protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor
      responders undergoing IVF-ET. METHODS: In this randomized controlled trial, 136
      women who responded poorly to GnRH agonist long protocol in their first IVF cycle
      were randomized into two equal groups using computer generated list and were
      treated in the second IVF cycle by either extended letrozole regimen (5 mg/day
      during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days)
      combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from
      cycle day 3-7) combined with HPuFSH-GnRHant protocol. RESULTS: There were no
      significant differences between both groups with regard to number of oocytes
      retrieved and clinical pregnancy rate (5.39 +/- 2.08 vs. 5.20 +/- 1.88 and 22.06%
      vs. 16.18%, respectively).The total gonadotropins dose and medications cost per
      cycle were significantly lower in extended letrozole group (44.87 +/- 9.16 vs.
      59.97 +/- 14.91 ampoules and 616.52 +/- 94.97 vs. 746.84 +/- 149.21 US Dollars
      ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole
      group and 4616 $ in short letrozole group. CONCLUSION: Extended letrozole
      regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole
      regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

PMID- 21714698
TI  - Malignant pheochromocytoma and paraganglioma: three cases illustrating the use of
      molecular targeted diagnostics and therapy and possible role of new drugs.

PMID- 21714699
TI  - Two occult cases of adult T-cell leukaemia/lymphoma.

PMID- 21714700
TI  - Mean platelet volume/platelet count ratio as a predictor of long-term mortality
      after non-ST-elevation myocardial infarction.
AB  - Previous studies reported an association between elevated mean platelet volume
      (MPV) and post-myocardial infarction mortality. This study explores the
      association between long-term mortality after non-ST-segment elevation myocardial
      infarction (NSTEMI) and the peripheral blood platelet indices (i.e., the mean
      platelet volume (MPV), platelet count, and the MPV/platelet (MPV/P) ratio). Two
      physicians independently reviewed the data of 619 NSTEMI patients. The blood
      samples were drawn and analyzed within 1 h of admission, the second, and the last
      hospital days. Patients were stratified into equal tertiles according to the
      platelet count, MPV, and MPV/platelet ratio. The primary outcome, 4-year all
      cause mortality, was compared among the platelet indices tertile models.
      According to MPV, platelet count, and MPV/platelet ratio tertile models, there
      was a trend of higher 4-year mortality for the lower and upper tertiles in
      comparison to the middle tertiles. However, only the admission MPV/platelet ratio
      tercile model was statistically significant for predicting the 4-year mortality.
      The mortality rate of the highest MPV/platelet (48/207 (23%)) and the lowest
      (41/206 (20%)) tertiles were significantly higher than the middle tertile (19/206
      (9%)), p = 0.0004 by the chi-squared test. After adjusting for Global Registry of
      Acute Coronary Events, the patients in the combined first and third MPV/P
      tertiles had higher mortality in reference to those in the middle MPV/P tercile
      (hazard ratio 1.951, confidence interval 1.032-3.687, and p < 0.0396). Our novel
      finding is that the MPV/platelet ratio is superior to the MPV alone in predicting
      long-term mortality after NSTEMI. We suggest that using this ratio will magnify
      any existing relationship between platelet indices and mortality post-NSTMI.
      Further studies are needed to confirm our finding.

PMID- 21714701
TI  - The association between coronary artery calcification and mean platelet volume in
      the general population.
AB  - Patients with coronary artery calcification have an increased risk of coronary
      vascular events and mortality. Coronary artery calcification can be quantified
      using the coronary calcium score (CCS) from multi-detected row computed
      tomography (MDCT), and the score is proportionally related to the severity of
      atherosclerotic disease. Mean platelet volume (MPV) is gaining interest as a new
      independent cardiovascular risk factor. Accordingly, the aim of our study was to
      evaluate the relationship between CCS and MPV in the general population. A total
      of 2116 individuals were enrolled from a health promotion center between July
      2007 and June 2010. Among them, 259 subjects were included in the final analysis.
      MDCT was used to measure CCS and CCS > 1 was defined as the presence of coronary
      calcification. The MPV value was significantly higher in the coronary artery
      calcification group than in the control group. Multivariate analyses showed that
      MPV was positively associated with coronary calcification (OR, 1.61; 95% CI 1.02
      2.55). In summary, there was a significant association between coronary artery
      calcification and MPV in the general population. Therefore, the detection of
      elevated MPV should alert clinicians to the coexistence of multiple underlying
      CVD risk factors warranting early evaluation and treatment.

PMID- 21714702
TI  - The novel platelet activation receptor CLEC-2.
AB  - The c-type lectin-like receptor 2 (CLEC-2) was first identified from a bio
      informatic screen for c-type lectin-like receptors. However, neither its function
      nor its ligand(s) had been elucidated for several years. In 2006, we reported
      that the receptor is expressed on the surface of platelets and serves as a
      receptor for the snake venom rhodocytin, which potently stimulates platelet
      aggregation. Since then CLEC-2 has been intensively investigated, and its
      endogenous/exogenous ligands and several physiological/pathological roles have
      been clarified. In this article and its accompanying poster, we outline the
      structure, distribution, signal transduction mechanism and functions of CLEC-2.

PMID- 21714703
TI  - The P makes the difference in plasma rich in growth factors (PRGF) technology.

PMID- 21714704
TI  - Platelet expression of CD62P in hypotrophic newborns.
AB  - BACKGROUND: Hypotrophic newborns demonstrate a reduced blood platelet count and
      therefore may have haemostasis disorders. The antigen density of CD62P on the
      surface of platelets may indicate the activation of blood platelets. MATERIALS
      AND METHODS: We have studied 31 hypotrophic newborns, and have divided these into
      two groups: weighing less than the 5th centile and between the 5th and 10th
      centiles. The antigen density of CD62P was calculated according to the procedure
      recommended by DAKO QIFIKIT. RESULTS: Hypotrophic newborns exhibited a median 22
      000 of CD62P per platelet. There is a distinct gender difference (female median
      29 768, male median 19 044 of CD62P per platelet, p = 0.001). Newborns below the
      5th centile demonstrated a median 30 000 of CD62P per platelet, whereas between
      the 5th and 10th centiles - a median 18 700. A negative correlation (R = -0.53, p
      = 0.002) was found between the antigen density of CD62P and birth weight.
      CONCLUSION: Hypotrophy affects the expression of CD62P. There is a negative
      correlation between the antigen density of CD62P and birth weight.

PMID- 21714705
TI  - Differences in illness-related knowledge of breast cancer patients according to
      their involvement in self-help groups.
AB  - OBJECTIVE. There is little evidence of the gain in illness-related knowledge
      obtained in breast cancer self-help groups. This paper seeks to explore whether
      participants in self-help groups know more about breast cancer than non
      participants and to examine the level of knowledge of leaders of self-help groups
      in comparison to the other two groups. METHODS. A sample of 727 women affected by
      breast cancer was interviewed with a self-administered questionnaire assessing
      knowledge on disease, prevention, and aftercare. The interviewing took place
      during three different surveys conducted between 2005 and 2009. The data of the
      second and third survey were used in order to create a larger data base and to
      include self-help group leaders. RESULTS. Participants in self-help groups knew
      significantly more than non-participants, although only in the subtests lymph
      edema and breast-examination. Leaders of support groups scored highest in all
      subtests. Involvement in a support group was most decisive for respondents'
      knowledge, but other factors such as age, education, and medical history also had
      effects. CONCLUSION. Self-help groups provide a considerable potential for
      acquiring illness-related knowledge. As the participation rate in German breast
      cancer self-help groups is still quite low, it seems reasonable to generate more
      interest in this kind of support.

PMID- 21714706
TI  - Clinical and metabolic evaluation of Korean patients with urolithiasis.
AB  - BACKGROUND: The purpose of the present study was to conduct a comprehensive
      evaluation of clinical and metabolic factors in order to determine the
      characteristics of urolithiasis in a Korean population, compared with other
      ethnic groups. In addition, clinical and metabolic factors associated with
      calcium oxalate (CaOx) and uric acid (UA) stone formation were compared. METHODS:
      A total of 211 Korean patients with urolithiasis were analysed. Biochemical
      components in 24-hour urine were determined and the relative supersaturation
      (RSS) was calculated using the EQUIL 3 software program. Physical analysis of
      stone composition using Fourier Transform-Infrared spectrometry (FT-IR), blood
      chemistry, and demographics were also investigated. RESULTS: A previous history
      of urolithiasis and male gender were found to be clinical risk factors related to
      urolithiasis. Metabolic abnormalities, including hypercalciuria, low urine
      volume, natriuresis, hypocitraturia, and hyperoxalaturia were commonly found in
      24-hour urine. Korean patients had higher calcium, lower citrate, lower
      phosphate, lower urine volume, and higher RSS with respect to UA than Caucasian
      patients. Patients with CaOx stone formation (n = 100) were younger and excreted
      a higher level of calcium and higher UA at a higher pH than patients with UA
      stones (n = 37). A significant difference in RSS was observed with respect to
      CaOx, while there was no significant difference in RSS with respect to UA between
      them. CONCLUSIONS: Metabolic abnormalities, including hypercalciuria, low urine
      volume, natriuresis, hypocitraturia, and hyperoxalaturia were important findings
      in Korean patients with urolithiasis. In addition, clinical and metabolic
      characteristics of CaOx stone formers differed in comparison with UA stone
      formers.

PMID- 21714707
TI  - Sulfite determination by an inhibitor biosensor-based mushroom (Agaricus
      bisporus) tissue homogenate.
AB  - The aim of the study presented here is to develop a biosensor based on mushroom
      (Agaricus bisporus) tissue homogenate for sensitive and economical determination
      of sulfite in foods. The working principle of the biosensor is based on an
      inhibition effect of sulfite on polyphenol oxidases in mushroom. Mushroom tissue
      homogenate was immobilized by gelatin and glutaraldehyde on a Clark-type oxygen
      electrode. Some optimization studies related to the bioactive layer components
      and working conditions were identified. The biosensor was applied to the food
      samples. The biosensor reported here was successfully allowed to analyze sulfite,
      which was a food additive in real food samples.

PMID- 21714708
TI  - How does linguistic complexity influence intelligibility in a German audiometric
      sentence intelligibility test?
AB  - OBJECTIVE: We investigated if linguistic complexity contributes to the variation
      of the speech reception threshold in noise (SRTN) and thus should be employed as
      an additional design criterion in sentence tests used for audiometry. DESIGN:
      Three test lists were established with sentences from the Gottingen sentence test
      ( Kollmeier & Wesselkamp, 1997 ). One list contained linguistically simple
      sentences, the other two lists contained sentences with two types of linguistic
      complexity. For each listener the SRTN was determined for each list. STUDY
      SAMPLE: Younger and older listeners with normal hearing and older listeners with
      hearing impairment were tested. RESULTS: Younger listeners with normal hearing
      showed significantly worse SRTNs on the complex lists than on the simple list.
      This difference could not be found for either of the older groups. CONCLUSIONS:
      The effect of linguistic complexity on speech recognition seems to depend on age
      and/or hearing status. Hence, pending further research, linguistic complexity
      seems less relevant as a sentence test design criterion for clinical-audiological
      purposes, but we argue that a test with larger variation in linguistic complexity
      across sentences might show a relation between linguistic complexity and speech
      recognition even in a clinical population.

PMID- 21714709
TI  - Prevalence of clinical referrals having hearing thresholds within normal limits.
AB  - OBJECTIVES: To document the prevalence of clinically normal air conduction
      thresholds (0.5-4 kHz, bilaterally, <=20 dB HL) among children and adults in a
      large audiology service and to estimate the prevalence of auditory processing
      disorder (APD). DESIGN: Over a period of one year, clinicians implemented their
      usual protocol and recorded a brief history for those with normal audiometry.
      STUDY SAMPLE: The number of people seen by the service was 2924 children (0-16
      years old) and 4757 adults (17-100 years old). RESULTS: Adults and school-age
      children were most commonly referred by their primary care doctor for
      difficulties listening in noise or following a conversation, and younger children
      by their home health visitor for speech production problems. Children tended to
      be referred on to speech pathology or APD clinics whereas adults were discharged.
      CONCLUSIONS: The prevalence of normal cases was 5.1% among the children and 0.9%
      among all adults. For younger adults (17-60 years, n = 1025), the prevalence was
      4.0%. Based on comparison with those referred with hearing loss, we estimate the
      prevalence of APD among children and adults, defined as listening problems
      despite normal audiometry, to be about 0.5-1.0% of the general population.

PMID- 21714710
TI  - Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion:
      bioequivalence of a new generic product with the branded product in healthy
      volunteers.
AB  - OBJECTIVE: Parenteral sodium ferric gluconate in complex (Ferrlecit [branded
      SFG]) is used to treat patients with iron deficiency anemia undergoing chronic
      hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic
      study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved
      generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded
      SFG) are bioequivalent. METHODS: In this open-label study, 240 healthy volunteers
      in a fasting state were assigned randomly to a single 10-min intravenous (IV)
      infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron
      concentrations were determined for the 36-h period after infusion and corrected
      for pretreatment levels. Maximum concentration (Cmax) and area under the
      concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two
      products. Demonstration of bioequivalence required that the 90% confidence
      intervals of each parameter evaluated for generic SFG were within 80% to 125% of
      the corresponding values for branded SFG. RESULTS: Uncorrected and baseline
      corrected mean serum concentrations of total serum iron during the 36-h
      assessment period were similar for generic and branded SFG. For total serum iron,
      the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For
      transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and
      92% for corrected AUC[0-36]. All associated 90% confidence intervals were within
      the range of 80% to 125%. CONCLUSIONS: A new generic SFG in complex for IV
      infusion is bioequivalent to the branded SFG in complex for IV infusion. The
      generic SFG is AB rated by the FDA and considered therapeutically equivalent to
      the branded product.

PMID- 21714711
TI  - Association between the changes in renal function and serum uric acid levels
      during multifactorial intervention and clinical outcome in patients with
      metabolic syndrome. A post hoc analysis of the ATTEMPT study.
AB  - AIM: To assess the effects of long-term multifactorial intervention on renal
      function and serum uric acid (SUA) levels and their association with estimated
      cardiovascular disease (eCVD) risk and actual CVD events. METHODS: This
      prospective, randomized, target-driven study included 1123 subjects (45.6% men,
      age 45-65 years) with metabolic syndrome (MetS) but without diabetes or CVD.
      Patients were randomized to multifactorial treatment. Atorvastatin was titrated
      from 10-80 mg/day aiming at a low density lipoprotein cholesterol (LDL-C) target
      of <100 mg/dl (group A) or an LDL-C target of <130 mg/dl (group B). Changes in
      estimated glomerular filtration rate (eGFR) and SUA levels were recorded in all
      patients and in the subgroup with stage 3 chronic kidney disease (CKD; eGFR = 30
      59 ml/min/1.73 m(2); n = 349). We used ANOVA to compare changes within the same
      group, unpaired Student t-test to compare results between groups at specific time
      points, and log-rank test to compare event free survival. RESULTS: The eCVD-risk
      reduction was greater in group A. In the overall study population, eGFR increased
      by 3.5% (p < 0.001) and SUA levels fell by 5.6% (p < 0.001). In patients from
      group A with stage 3 CKD (group A1; n = 172), eGFR increased by 11.1% (p < 0.001)
      from baseline and by 7.5% (p < 0.001) in group B1 (n = 177; p < 0.001 vs. the
      change in group A1). The corresponding fall in SUA levels was 10.7% in group A1
      (p < 0.001 vs. baseline) and 8.3% in group B1 (p < 0.001 vs. baseline and group
      A1). These changes were mainly attributed to atorvastatin treatment. Among the
      CKD stage 3 patients there were no CVD events in group A1, while 6 events
      occurred in group B1 (p = 0.014). CONCLUSIONS: Multifactorial intervention in
      patients with MetS without established CVD improved renal function and reduced
      SUA levels. These changes were more prominent in stage 3 CKD patients and might
      have contributed to the reduction in eCVD risk and clinical events. Original
      study registration number [ClinicalTrials.gov ID: NCT00416741].

PMID- 21714721
TI  - Antipsychotic-induced hyperprolactinaemia.
AB  - BACKGROUND AND OBJECTIVES: Antipsychotic medications are a potential cause of
      hyperprolactinaemia and may be implicated in the development of pituitary
      adenomas. This review examines the effect of different antipsychotic medications
      on prolactin and sexual function, and provides practical guidelines for
      investigation and management of antipsychotic-induced hyperprolactinaemia.
      METHOD: Literature review. RESULTS AND CONCLUSIONS: Antipsychotic-induced
      hyperprolactinaemia occurs overall in up to 70% of patients with schizophrenia,
      depending on the medications used. It is associated with significant levels of
      hypogonadism and sexual dysfunction, which in general relates to the degree of
      prolactin elevation. A consequence of the hypogonadism is clinically significant
      bone loss which may lead to osteoporosis and increased risk of minimal trauma
      fracture. Where the potentially offending drug cannot be safely withdrawn to
      document a normal prolactin, imaging with MRI should be undertaken to exclude a
      structural pituitary lesion. The management strategy of choice is switching to a
      prolactin-sparing antipsychotic. Sex steroid replacement can reverse many of the
      adverse effects including the hypogonadal symptoms and bone loss. Low dose
      dopamine agonist therapy should be used with caution as a third line treatment,
      since there have been cases of dopamine agonist-induced exacerbation of
      psychosis. There is a need for a randomised controlled trial of low dose dopamine
      agonist therapy versus sex steroid replacement to establish the relative safety
      and efficacy of each approach.

PMID- 21714722
TI  - Risk assessment: predicting physical aggression in child psychiatric inpatient
      units.
AB  - OBJECTIVE: The aim of this study was to examine the predictive validity of
      unstructured clinical risk assessment and associated risk factors for aggression
      in predicting physical aggression in children admitted to an Australian
      psychiatric inpatient facility. METHOD: A retrospective review of patient records
      was conducted at the State Wide Child Inpatient Unit during late 2009 for the
      period September 2006-July 2009. Children between the ages of 8 and 13 were
      included in analyses. Information collected included admission risk assessment
      ratings, critical incident reports, patient diagnoses and history of aggression
      and trauma. RESULTS: A total of 127 children (aged 8-13 years) were included in
      retrospective analyses. Higher aggression risk rankings were predictive of the
      frequency but not the severity of aggression. A diagnosis of a disruptive
      behaviour disorder and a history of being a victim of trauma were also predictive
      of engagement in aggression; however, were not as predictive as the risk
      assessment. A high risk assessment rating for aggression was better able to
      predict engagement in aggressive behaviour than a history of physical aggression
      alone. CONCLUSIONS: Based on professional expertise, prior experience and
      intuition, clinicians were able to successfully predict engagement in aggressive
      behaviour during patient admission to a child psychiatric inpatient units.

PMID- 21714724
TI  - Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory
      response in airway mucosa.
AB  - AIMS: Airway mucosa is constantly exposed to various airborne microbes, and
      epithelial host defense requires a robust innate immunity. Recently, it has been
      suggested that NADPH oxidase (NOX) isozymes serve functional roles in toll-like
      receptor (TLR)-mediated innate immune responses. However, the molecular mechanism
      between TLR and NOX-mediated reactive oxygen species (ROS) production in human
      airway mucosa has been poorly understood. RESULTS: Here, we show that flagellin
      induced ROS generation is dependent on dual oxidase 2 (DUOX2) activation, which
      is regulated by [Ca(2+)](i) mobilization in primary normal human nasal epithelial
      (NHNE) cells. Interestingly, we observed that silencing of DUOX2 expression in
      NHNE cells and nasal epithelium of Duox2 knockout mice failed to trigger mucin
      and MIP-2? production upon challenging flagellin. INNOVATION: Our observation in
      this study reveals that flagellin-induced hydrogen peroxide (H(2)O(2)) generation
      is critical for TLR5-dependent innate immune responses, including IL-8 production
      and MUC5AC expression in the nasal epithelium. Furthermore, DUOX2-mediated
      H(2)O(2) generation activated by the flagellin-TLR5 axis might serve as a novel
      therapeutic target for infectious inflammation diseases in the airway tract.
      CONCLUSION: Taken together, we propose that DUOX2 plays pivotal roles in TLR5
      dependent inflammatory response of nasal airway epithelium.

PMID- 21714725
TI  - Comparison of the in vitro release characteristics of mucosal freeze-dried wafers
      and solvent-cast films containing an insoluble drug.
AB  - Drug release characteristics of freeze-dried wafers and solvent-cast films
      prepared from sodium carboxymethylcellulose have been investigated and compared.
      In vitro drug dissolution studies were performed using an exchange cell and drug
      release was measured by UV spectroscopy at 272 nm using distilled water. The
      dissolution profiles of hydrochlorothiazide from the wafers and films were
      compared by determining the rates of drug release, estimated from the % release
      versus time profiles and calculating their difference (f(1)) and similarity
      (f(2)) factors. The effects of drug loading, polymer content and amount of
      glycerol (GLY) (films) on the drug release characteristics of both formulations
      were investigated. Both the wafers and films showed sustained type release
      profiles that were best explained by the Korsmeyer-Peppas equation. Changes in
      the concentration of drug and GLY (films) did not significantly alter the release
      profiles whilst increasing polymer content significantly decreased the rate of
      drug release from both formulations. The rate of release was faster from the
      wafers than the corresponding films which could be attributed to differences in
      the physical microstructure. The results show the potential of employing both
      formulations in various mucosal drug delivery applications.

PMID- 21714726
TI  - Participation restrictions at work indicate participation restrictions in other
      domains of life.
AB  - Health problems are often associated with activity limitations and participation
      restrictions, as defined in the International Classification of Functioning,
      Disability and Health (ICF). This often affects the workplace in the form of sick
      leave or a reduction in productivity. The question is, "to what extent are
      participation restrictions at work related to participation restrictions in other
      domains of life?" A total of 382 primary health care patients (aged 18-65) were
      asked to provide information on their employment status, perceived health-related
      workplace problems and sick leave status. Health-dependent participation
      restrictions across different domains of life were assessed using the Index for
      Measuring Participation Restrictions (IMET) self rating questionnaire. Currently
      unemployed patients reported significantly higher degrees of participation
      restrictions across all domains of life than the employed participants. Employed
      patients with workplace problems scored higher than patients without workplace
      problems. The domain of work encompassed the highest level of impairment, while
      the lowest was observed in personal relationships. Workplace problems occur
      frequently for primary health care patients. They coincide with participation
      restrictions in other domains of life. For patients who complain about their
      capacity to work, diagnosis and treatment must not only focus on the work domain,
      but also enquire into and consider participation restrictions in other domains of
      life.

PMID- 21714727
TI  - A novel 8.O.6'-neolignan from Taxillus theifer.
AB  - A new 8.O.6'-neolignan, threo-(7R, 8R)-7-acetoxy-3',4'-dimethoxy-3,4-dimethoxy
      Delta-(8')-8.O.6'-neolignan (1) along with two known lignans (2) and (3), was
      isolated from the leaves and stems of Taxillus theifer. Structural elucidation
      was carried out by 1-D and 2-D-NMR spectroscopic methods, and the absolute
      configurations of C-7 and C-8 in 1 were determined on the basis of circular
      dichroism. Compound 2 is threo-7-acetoxy-3'-methoxy-3,4-dimethoxy-Delta-(7')
      8.O.4'-neolignan obtained from a natural source for the first time, previously
      derived from a synthesis study of 8,4'-oxyneolignans.

PMID- 21714728
TI  - High-performance thin layer chromatographic quantification of bioactive psoralen
      and daidzein in leaves of Ficus carica L.
AB  - This study was undertaken to quantify psoralen and daidzein by high-performance
      thin layer chromatography (HPTLC). The methanolic extract of 10 mg mL(-1)
      concentration solution was prepared for HPTLC quantification of psoralen and
      daidzein. HPTLC aluminium-backed plates coated with 0.2 mm layers of silica gel
      60 F(254) were used as the stationary phase. The working standard solution of
      psoralen and daidzein was applied along with the test sample solution by means of
      Camag Linomat IV sample applicator. R (f) values of psoralen and daidzein were
      found to be 0.60 and 0.88, whilst as their percentage values in methanolic
      extract were found to be 3.02% and 5.64% (w/w), respectively. A simple
      quantitative estimation method of psoralen and daidzein by HPTLC is reported that
      can be used for the quality control of marketed preparations containing Ficus
      carica. However, further study is warranted to isolate and quantify active
      constituents present in the leaves of F. carica by sophisticated techniques.

PMID- 21714729
TI  - Antioxidant activity and cytotoxic effect of aviprin and aviprin-3"-O-D
      glucopyranoside on LNCaP and HeLa cell lines.
AB  - Many researchers have shown that plant-derived polyphenolic compounds are helpful
      nutraceuticals in restraining various disorders such as neoplastic diseases. In
      this study two linear furanocoumarins, aviprin and aviprin-3"-O-D-glucopyranoside
      (A3G), were isolated from methanol extract of Prangos uloptera roots. The
      evaluation of free radical scavenging capacity of the compounds showed that
      aviprin is a more effective antioxidant than A3G with RC50 of 0.54 mg mL-1. The
      biological and antiproliferative activities of the furanocoumarins were examined
      using human cervical carcinoma HeLa cell line and LNCaP prostatic cell line. Cell
      membrane integrity and cell viability were evaluated by measuring trypan blue
      exclusion assay and reduction of the tetrazolium blue compound, respectively.
      Treating the LNCaP cell line with various concentrations of the furanocoumarins
      showed that IC50 of aviprin and A3G were 0.4 and 6.6 mg mL-1, whereas their CC50
      values were 0.7 and 11 mg mL-1, respectively. These results indicated that 42.7%
      of LNCaP cells were not dead by necrosis. Treating the HeLa cells by the
      furanocoumarins showed the greater sensitivity of the HeLa cell line than the
      LNCaP cell line. A morphological analysis and the study of DNA fragmentation
      provided further some evidence for the inhibition of the LNCaP cell line via
      apoptosis induction.

PMID- 21714730
TI  - Propolis oil extract: quality analysis and evaluation of its antimicrobial
      activity.
AB  - Designing propolis products for external use involves determining the optimal
      form of propolis for the introduction into dermatological pharmaceuticals and
      cosmetic preparations. As a potent ingredient, propolis oil extract from raw
      material harvested in Lithuania was analysed. The rheological characteristics,
      content of phenolic compounds, major compounds and antimicrobial activity of the
      propolis oil extract are investigated here for the first time. The propolis oil
      extract was produced by maceration using different solvents, raw material was
      collected in Lithuania. Solvent mixture with 96% ethanol increased the
      rheological stability and extracted amount of phenolic compound. High-performance
      liquid chromatography identified the potent quality markers for Lithuanian
      propolis, phenylpropanoid vanillin, coumaric acid and ferulic acid. Antimicrobial
      activity of propolis oil extract was evaluated in experimental studies in vitro,
      and the minimal concentration of phenolic compounds that inhibited respective
      microorganisms was determined. The results demonstrate that phenolic compounds
      have effective antimicrobial activity in propolis oil extract; thus, it can be
      compatible with the semisolid preparation.

PMID- 21714731
TI  - Optimisation of preparation conditions and properties of phytosterol liposome
      encapsulating nattokinase.
AB  - Phytosterol liposomes were prepared using the thin film method and used to
      encapsulate nattokinase (NK). In order to obtain a high encapsulation efficiency
      within the liposome, an orthogonal experiment (L9 (3)(4)) was applied to optimise
      the preparation conditions. The molar ratio of lecithin to phytosterols, NK
      activity and mass ratio of mannite to lecithin were the main factors that
      influenced the encapsulation efficiency of the liposomes. Based on the results of
      a single-factor test, these three factors were chosen for this study. We
      determined the optimum extraction conditions to be as follows: a molar ratio of
      lecithin to phytosterol of 2 : 1, NK activity of 2500 U mL-1 and a mass ratio of
      mannite to lecithin of 3 : 1. Under these optimised conditions, an encapsulation
      efficiency of 65.25% was achieved, which agreed closely with the predicted
      result. Moreover, the zeta potential, size distribution and microstructure of the
      liposomes prepared were measured, and we found that the zeta potential was -51 +/
      3 mV and the mean diameter was 194.1 nm. From the results of the scanning
      electron microscopy, we observed that the phytosterol liposomes were round and
      regular in shape and showed no aggregation.

PMID- 21714732
TI  - QSPR for predicting chloroform formation in drinking water disinfection.
AB  - Chlorination is the most widely used technique for water disinfection, but may
      lead to the formation of chloroform (trichloromethane; TCM) and other by
      products. This article reports the first quantitative structure-property
      relationship (QSPR) for predicting the formation of TCM in chlorinated drinking
      water. Model compounds (n = 117) drawn from 10 literature sources were divided
      into training data (n = 90, analysed by five-way leave-many-out internal cross
      validation) and external validation data (n = 27). QSPR internal cross-validation
      had Q2 = 0.94 and root mean square error (RMSE) of 0.09 moles TCM per mole
      compound, consistent with external validation Q2 of 0.94 and RMSE of 0.08 moles
      TCM per mole compound, and met criteria for high predictive power and robustness.
      In contrast, log TCM QSPR performed poorly and did not meet the criteria for
      predictive power. The QSPR predictions were consistent with experimental values
      for TCM formation from tannic acid and for model fulvic acid structures. The
      descriptors used are consistent with a relatively small number of important TCM
      precursor structures based upon 1,3-dicarbonyls or 1,3-diphenols.

PMID- 21714733
TI  - A new isoflavone from the mangrove endophytic fungus Fusarium sp. (ZZF60).
AB  - A new isoflavone, 5-hydroxy-7-methoxy-4'-O-(3-methylbut-2-enyl) isoflavone (1),
      together with five known compounds, eriodictyol (2), vittarin-B (3), 3,6,7
      trihydroxy-1-methoxyxanthone (4), 1,3,6-Trihydroxy-8-methylxanthone (5) and cyclo
      (Phe-Tyr) (6), was isolated from the mangrove endophytic fungus, Fusarium sp.
      ZZF60 obtained from the South China Sea. Their structures were determined by the
      analysis of spectroscopic data.

PMID- 21714734
TI  - Polyphenolics profile and antioxidant properties of Raphanus sativus L.
AB  - Raphanus sativus, a common cruciferous vegetable has been attributed to possess a
      number of pharmacological properties. Antioxidant and radical scavenging activity
      of R. sativus root extracted with solvents of varying polarity were evaluated
      using different model systems. Polyphenolic content was estimated to be in the
      range 13.18-63.54 mg g-1 dry weight, with a considerable amount being obtained
      with polar solvents. High-performance liquid chromatography analysis indicated
      the presence of an array of polyphenolics. Catechin was found to be the most
      abundant phenolic compound in water extract and sinapic acid, the predominant
      phenolic compound in methanolic, ethyl acetate and hexane extracts. The
      methanolic extract showed significant ferric reducing ability, moderate metal
      chelating activity and strong radical scavenging activity. The methanolic extract
      could be successfully utilised as an ingredient in functional foods. However,
      water extract could be more pertinent to human nutrition as it contained a
      significant amount of catechin, which was comparable to traditional sources like
      green and black tea.

PMID- 21714735
TI  - QSAR analysis of the toxicity of nitroaromatics in Tetrahymena pyriformis:
      structural factors and possible modes of action.
AB  - The Hierarchical Technology for Quantitative Structure-Activity Relationships
      (HiT QSAR) was applied to 95 diverse nitroaromatic compounds (including some
      widely known explosives) tested for their toxicity (50% inhibition growth
      concentration, IGC50) against the ciliate Tetrahymena pyriformis. The dataset was
      divided into subsets according to putative mechanisms of toxicity. The
      Classification and Regression Trees (CART) approach implemented within HiT QSAR
      has been used for prediction of mechanism of toxicity for new compounds. The
      resulting models were shown to have ~80% accuracy for external datasets
      indicating that the mechanistic dataset division was sensible. The Partial Least
      Squares (PLS) statistical approach was then used to develop 2D QSAR models.
      Validated PLS models were explored to: (1) elucidate the effects of different
      substituents in nitroaromatic compounds on toxicity; (2) differentiate compounds
      by probable mechanisms of toxicity based on their structural descriptors; and (3)
      analyse the role of various physical-chemical factors responsible for compounds'
      toxicity. Models were interpreted in terms of molecular fragments promoting or
      interfering with toxicity. It was also shown that mutual influence of
      substituents in benzene ring plays the determining role in toxicity variation.
      Although chemical mechanism based models were statistically significant and
      externally predictive (r2(ext) = 0.64 for the external set of 63 nitroaromatics
      identified after all calculations have been completed), they were also shown to
      have limited coverage (57% for modelling and 76% for external set).

PMID- 21714736
TI  - Double dissociations of word and number processing in auditory and written
      modalities: a case study.
AB  - We report an individual with a massive left-hemisphere lesion, who showed reverse
      patterns of dissociations between word and number processing in two modalities
      (auditory comprehension and written production). His performance in auditory
      comprehension was perfect for words, but severely impaired for numbers. In
      written production, he performed significantly better at writing numbers (both
      Arabic numbers and word numbers) than writing words. His visual comprehension
      fell into normal range for words and numbers while his oral production was at
      floor for both. This case profile adds further evidence to the functional/neural
      segregation of word and number processing systems.

PMID- 21714737
TI  - Composition of essential oil and antioxidant capacity of Centaurea drabifolia Sm.
      subsp. detonsa (Bornm.) Wagenitz, endemic to Turkey.
AB  - In this study, composition of essential oil and antioxidant capacity of Centaurea
      drabifolia subsp. detonsa were investigated. The antioxidant capacity of the
      methanolic extract was evaluated by various methods including measuring the total
      phenolic content, total antioxidant capacity, free radical scavenging activity
      (DPPH assay), beta-carotene/linoleic acid bleaching assay and ferric and cupric
      ion reducing power assay. The composition of essential oil was identified by
      using gas chromatography-mass spectrometry. Totally, 41 compounds were described
      in the essential oil. Germacrene D (44.829%) was determined as the major compound
      of the essential oil. The total phenolic content, total antioxidant capacity,
      inhibition rate of oxidation of linoleic acid, IC(50) (in DPPH assay) and EC(50)
      (in reducing power) value were found to be 40.454 mg GAE/g, 100.840 mg AAE/g,
      65.639%, 39.584 ug mL(-1) and 0.603 mg mL(-1), respectively. The results
      indicated that the extract of C. drabifolia subsp. detonsa has strong antioxidant
      properties and this species can be used as a natural antioxidant in food
      processing and pharmaceutical industries.

PMID- 21714738
TI  - Musical anhedonia: selective loss of emotional experience in listening to music.
AB  - Recent case studies have suggested that emotion perception and emotional
      experience of music have independent cognitive processing. We report a patient
      who showed selective impairment of emotional experience only in listening to
      music, that is musical anhednia. A 71-year-old right-handed man developed an
      infarction in the right parietal lobe. He found himself unable to experience
      emotion in listening to music, even to which he had listened pleasantly before
      the illness. In neuropsychological assessments, his intellectual, memory, and
      constructional abilities were normal. Speech audiometry and recognition of
      environmental sounds were within normal limits. Neuromusicological assessments
      revealed no abnormality in the perception of elementary components of music,
      expression and emotion perception of music. Brain MRI identified the infarct
      lesion in the right inferior parietal lobule. These findings suggest that
      emotional experience of music could be selectively impaired without any
      disturbance of other musical, neuropsychological abilities. The right parietal
      lobe might participate in emotional experience in listening to music.

PMID- 21714739
TI  - Steroid-responsive encephalopathy subsequently associated with Alzheimer's
      disease pathology: a case series.
AB  - BACKGROUND: Steroid-responsive encephalopathies can be considered vasculitic or
      non-vasculitic. Clinicopathological studies of non-vasculitic steroid-responsive
      encephalopathy are unusual, but can explain the range of diagnoses consistent
      with a steroid-responsive presentation in life. OBJECTIVE: To extend the range of
      clinical features and pathological findings consistent with steroid-responsive
      encephalopathy. Design, methods, and patients: A clinicopathological case series
      of four patients (two women, ages 54-71 years) with steroid-responsive
      encephalopathy followed at this institution until the time of death. RESULTS:
      Clinical features were suggestive of Creutzfeld-Jakob disease (CJD), dementia
      with Lewy bodies (DLB), and parkinsonism, but pathological examination revealed
      only Alzheimer's disease-related findings without evidence of Lewy bodies or
      prion disease in all cases. All patients demonstrated marked, sustained
      improvement following steroid treatment, based on clinical, magnetic resonance
      imaging, and/or electroencephalogram studies. Alzheimer's disease was not
      diagnosed in life due to the atypical clinical features, lack of hippocampal
      atrophy on brain imaging, and a dramatic symptomatic response to steroids.
      CONCLUSIONS: Steroid-responsive encephalopathy is the clinical presentation of
      some patients with Alzheimer's disease-related pathology at autopsy, and can be
      consistent with the clinical diagnoses of parkinsonism, DLB, or CJD disease in
      life.

PMID- 21714740
TI  - Impaired event memory and recollection in a case of developmental amnesia.
AB  - A current debate in the literature is whether all declarative memories and
      associated memory processes rely on the same neural substrate. Here, we show that
      H.C., a developmental amnesic person with selective bilateral hippocampal volume
      loss, has a mild deficit in personal episodic memory, and a more pronounced
      deficit in public event memory; semantic memory for personal and general
      knowledge was unimpaired. This was accompanied by a subtle difference in
      impairment between recollection and familiarity on lab-based tests of recognition
      memory. Strikingly, H.C.'s recognition did not benefit from a levels-of
      processing manipulation. Thus, not all types of declarative memory and related
      processes can exist independently of the hippocampus even if it is damaged early
      in life.

PMID- 21714741
TI  - Geissoschizine methyl ether, a corynanthean-type indole alkaloid from Uncaria
      rhynchophylla as a potential acetylcholinesterase inhibitor.
AB  - Geissoschizine methyl ether (1), a newly discovered strong acetylcholinesterase
      (AChE) inhibitor, along with six weakly active alkaloids, vallesiachotamine (2),
      hisuteine (3), hirsutine (4), isorhynchophylline (5), cisocorynoxeine (6) and
      corynoxeine (7) have been isolated from Uncaria rhynchophylla. Geissoschizine
      methyl ether (1) inhibited 50% of AChE activity at concentrations of 3.7 +/- 0.3
      ug mL(-1) while the IC(50) value of physostigmine as a standard was 0.013 +/-
      0.002 ug mL(-1). The mode of AChE inhibition by 1 was reversible and non
      competitive. In addition, molecular modelling was performed to explore the
      binding mode of inhibitor 1 at the active site of AChE.

PMID- 21714742
TI  - A large, searchable, web-based database of aphasic performance on picture naming
      and other tests of cognitive function.
AB  - Many research questions in aphasia can only be answered through access to
      substantial numbers of patients and to their responses on individual test items.
      Since such data are often unavailable to individual researchers and institutions,
      we have developed and made available the Moss Aphasia Psycholinguistics Project
      Database: a large, searchable, web-based database of patient performance on
      psycholinguistic and neuropsychological tests. The database contains data from
      over 240 patients covering a wide range of aphasia subtypes and severity, some of
      whom were tested multiple times. The core of the archive consists of a detailed
      record of individual-trial performance on the Philadelphia (picture) Naming Test.
      The database also contains basic demographic information about the patients and
      patients' overall performance on neuropsychological assessments as well as tests
      of speech perception, semantics, short-term memory, and sentence comprehension.
      The database is available at http://www.mappd.org/ .

PMID- 21714743
TI  - Emotion is not just an alarm bell--it's the whole tootin' fire truck.

PMID- 21714744
TI  - The effect of information distribution on collaborative inhibition.
AB  - Two experiments examined collaborative memory for information that was studied by
      all group members (shared items) and information that was studied by only a
      subset of group members (unshared items). In both experiments significant
      collaborative inhibition (reduced output of the collaborative groups relative to
      the pooled output of individuals) was obtained for both shared and unshared
      information. In Experiment 1 the magnitude of collaborative inhibition was larger
      for unshared items than for shared items, possibly because unshared items were
      less likely to be acknowledged and thus incorporated into the groups' recall. In
      Experiment 2 the magnitude of collaborative inhibition for shared and unshared
      information was equivalent once all participants were provided with the category
      name associated with the shared and unshared items. The results of the
      experiments are discussed in relation to the retrieval strategy disruption
      hypothesis of collaborative inhibition and the role of social process variables,
      such as acknowledgement, in influencing collaborative inhibition across
      situations involving memory of shared and unshared information.

PMID- 21714746
TI  - Social neuroscience: the social brain, oxytocin, and health.
AB  - Complex social behaviors allow various social organisms to create emergent
      organizations that extend beyond the individual. Social neuroscience is a
      burgeoning field that strives to understand the genetic, hormonal, and neural
      mechanisms responsible for these social structures and behaviors. Consequently,
      social neuroscience is highly interdisciplinary in nature and embraces the
      application of methods ranging from the molecular to the molar to investigate the
      reciprocal interactions between biological, cognitive, and social levels of
      analysis. The broad scope of such an endeavor introduces particular challenges
      associated with the integration of multiple levels of analysis. In the present
      mini-review, we highlight some recent findings in the field of social
      neuroscience and demonstrate the potential benefits of applying multilevel
      integrative analysis to the study of social behavior and its influence on
      physiology and health.

PMID- 21714745
TI  - Changes in frontal-parietal activation and math skills performance following
      adaptive number sense training: preliminary results from a pilot study.
AB  - Number sense is believed to be critical for math development. It is putatively an
      implicitly learned skill and may therefore have limitations in terms of being
      explicitly trained, particularly in individuals with altered neurodevelopment. A
      case series study was conducted using an adaptive, computerised programme that
      focused on number sense and general problem-solving skills. The study was
      designed to investigate training effects on performance as well as brain function
      in a group of children with Turner syndrome who are at risk for math difficulties
      and altered development of math-related brain networks. Standardised measurements
      of math and math-related cognitive skills as well as functional magnetic
      resonance imaging (fMRI) were used to assess behavioural and neurobiological
      outcomes following training. Participants demonstrated significantly increased
      basic math skills, including number sense, and calculation as well as processing
      speed, cognitive flexibility and visual-spatial processing skills. With the
      exception of calculation, increased scores also were clinically significant
      (i.e., recovered) based on reliable change analysis. Participants additionally
      demonstrated significantly increased bilateral parietal lobe activation and
      decreased frontal-striatal and mesial temporal activation following the training
      programme. These findings show proof of concept for an accessible training
      approach that may be potentially associated with improved number sense, math and
      related skills, as well as functional changes in math-related neural systems,
      even among individuals at risk for altered brain development.

PMID- 21714747
TI  - Kill Bill! Ugandan human rights organizations' attempts to influence the media's
      coverage of the Anti-Homosexuality Bill.
AB  - The Ugandan Anti-Homosexuality Bill of October 2009 caused an international
      outcry and sparked intense debate in the local and international media.
      Particularly contentious was its proposal to impose the death penalty for acts of
      'aggravated homosexuality'. Through a quantitative content analysis of 176 items
      from two main daily newspapers, the government-owned New Vision and the privately
      owned Daily Monitor, over the period October 2009-June 2010, combined with
      qualitative interviews with human rights defenders in Uganda, this study explores
      attempts made by local human rights advocates to influence the media's coverage
      of the Bill and the extent to which these attempts were successful. The study
      finds that while there are significant differences between the frequency of
      reporting on the Bill in the two newspapers, both papers devoted little editorial
      space to the public health and human rights concerns put forward by local human
      rights organizations. Despite Uganda's recent and often lauded history of openly
      addressing HIV/AIDS, human right organizations' attempts to highlight the Bill's
      potentially adverse effects on the country's ability to tackle the epidemic
      effectively were only partially successful and, interestingly, awarded much less
      attention than the potential human rights implications of the proposed change in
      legislation.

PMID- 21714748
TI  - Life goals after brain injury in the light of the dual process approach:
      empirical evidence and implications for neuropsychological rehabilitation.
AB  - Sequelae of acquired brain injury endanger the realisation of important life
      goals. Discrepancies arise between the importance attached to a goal and the
      success in realising it. This study investigates goal discrepancies and their
      influence on patients' subjective well-being (SWB) in different rehabilitation
      stages. Life-goals, SWB and daily functioning were assessed in 130 neurological
      inpatients and 42 outpatients by self-report questionnaires. Both patient groups
      reported greater discrepancies between importance and success of life-goals than
      a normative sample of healthy controls. In multiple regression modelling, goal
      discrepancy predicted SWB in the inpatient sample even when controlling for the
      influence of ABI-related functional limitations. Of significant influence were
      the discrepancies in the domains of intimacy and achievement. In the respective
      analysis of the outpatient sample, goal discrepancy was not a significant
      predictor of SWB when accounting for functional limitations. A post-hoc analysis
      examined the inter-relation between functional limitations and goal discrepancy.
      Functional limitations influenced the ratings of successful goal realisation, yet
      they had less impact on the importance attached to a goal. The findings highlight
      the importance of patients' life-goals for successful neuropsychological
      rehabilitation. They indicate a need for further research considering goal
      adjustment processes in the face of chronic functional impairment.

PMID- 21714749
TI  - New QSAR prediction models derived from GPCR CB2-antagonistic triaryl bis-sulfone
      analogues by a combined molecular morphological and pharmacophoric approach.
AB  - In order to build quantitative structure-activity relationship (QSAR) models for
      virtual screening of novel cannabinoid CB2 ligands and hit ranking selections, a
      new QSAR algorithm has been developed for the cannabinoid ligands, triaryl bis
      sulfones, using a combined molecular morphological and pharmacophoric search
      approach. Both pharmacophore features and shape complementarity were considered
      using a number of molecular descriptors, including Surflex-Sim similarity and
      Unity Query fit, in addition to other molecular properties such as molecular
      weight, ClogP, molecular volume, molecular area, molecular polar volume,
      molecular polar surface area and dipole moment. Subsequently, partial least
      squares regression analyses were carried out to derive QSAR models linking
      bioactivity and the descriptors mentioned, using a training set of 25 triaryl bis
      sulfones. Good prediction capability was confirmed for the best QSAR model by
      evaluation against a test set of a further 20 triaryl bis-sulfones. The
      pharmacophore and molecular shape-based QSAR scoring function now established can
      be used to predict the biological properties of virtual hits or untested
      compounds obtained from ligand-based virtual screenings.

PMID- 21714750
TI  - How to discover modules in mind and brain: the curse of nonlinearity, and
      blessing of neuroimaging. A comment on Sternberg (2011).
AB  - Sternberg (2011) elegantly formalizes how certain sets of hypotheses,
      specifically modularity and pure or composite measures, imply certain patterns of
      behavioural and neuroimaging data. Experimentalists are often interested in the
      converse, however: whether certain patterns of data distinguish certain
      hypotheses, specifically whether more than one module is involved. In this case,
      there is a striking reversal of the relative value of the data patterns that
      Sternberg considers. Foremost, the example of additive effects of two factors on
      one composite measure becomes noninformative for this converse question. Indeed,
      as soon as one allows for nonlinear measurement functions and nonlinear module
      processes, even a cross-over interaction between two factors is noninformative in
      this respect. Rather, one requires more than one measure, from which certain data
      patterns do provide strong evidence for multiple modules, assuming only that the
      measurement functions are monotonic. If two measures are not monotonically
      related to each other across the levels of one or more experimental factors, then
      one has evidence for more than one module (i.e., more than one nonmonotonic
      transform). Two special cases of this are illustrated here: a "reversed
      association" between two measures across three levels of a single factor, and
      Sternberg's example of selective effects of two factors on two measures.
      Fortunately, functional neuroimaging methods normally do provide multiple
      measures over space (e.g., functional magnetic resonance imaging, fMRI) and/or
      time (e.g., electroencephalography, EEG). Thus to the extent that brain modules
      imply mind modules (i.e., separate processors imply separate processes), the
      performance data offered by functional neuroimaging are likely to be more
      powerful in revealing modules than are the single behavioural measures (such as
      accuracy or reaction time, RT) traditionally considered in psychology.

PMID- 21714751
TI  - Test-retest reliability of a new executive function battery for use in early
      childhood.
AB  - This study reported test-retest reliability for a newly developed executive
      function battery designed for use in early childhood. A total of 140
      predominantly low-income children (M = 48.1 months; 51% male; 43% African
      American) completed up to six tasks on two occasions an average of 18 (Mdn = 16)
      days apart. Pearson correlations between individual task scores indicated
      moderate retest reliability (mean r = .60; range = .52-.66) similar to that
      observed in other retest studies of executive function in preschool, school-aged,
      and adult samples. In contrast, confirmatory factor analyses of performance on
      the task battery across time indicated high retest reliability (phi = .95) that
      was identical to that observed in a recent study that used an identical method
      involving a sample of older adults. The short-term test-retest reliability of
      executive function in early childhood is comparable to that observed in childhood
      and adult samples. The retest reliability of children's performance on batteries
      of executive function tasks is appreciably stronger than the retest reliability
      of their performance on individual tasks. Studies that focus on inter- and
      intraindividual differences in executive function would be better served by using
      scores that are derived from task batteries than those derived from individual
      tasks.

PMID- 21714753
TI  - Superstition, witchcraft and HIV prevention in sub-Saharan Africa: the case of
      Ghana.
AB  - Belief in superstition and witchcraft is central to many African conceptions of
      illness, disease causation and etiology. While a number of anthropological
      studies have alluded to a theoretical link between such beliefs and HIV
      prevention in particular, there is limited empirical assessment of the
      association. Using data from the 2008 Ghana Demographic and Health Survey and
      applying random-effects logit models, we investigate whether the belief that AIDS
      can spread through witchcraft associates with the sexual decision making of never
      married men and women. The results show that men who believed AIDS can spread
      through witchcraft and other supernatural means were less likely to have used
      condoms at last sexual intercourse, controlling for other socioeconomic and
      cultural variables. Women with similar beliefs were more likely to have
      experienced sexual intercourse but less likely to have used condoms at last sex.
      For women, however, the relationship between such superstitious beliefs and
      condom use was somewhat attenuated after controlling for ethnicity and region of
      residence. From a policy perspective, the findings suggest that local beliefs
      regarding AIDS causation must be considered in designing HIV/AIDS programmes and
      interventions.

PMID- 21714754
TI  - Do children with dyslexia and/or specific language impairment compensate for
      place assimilation? Insight into phonological grammar and representations.
AB  - English speakers have to recognize, for example, that te[m] in te[m] pens is a
      form of ten, despite place assimilation of the nasal consonant. Children with
      dyslexia and specific language impairment (SLI) are commonly proposed to have a
      phonological deficit, and we investigate whether that deficit extends to place
      assimilation, as a way of probing phonological representations and phonological
      grammar. Children with SLI plus dyslexia, SLI only, and dyslexia only listened to
      sentences containing a target word in different assimilatory contexts-viable,
      unviable, and no change-and pressed a button to report hearing the target. The
      dyslexia-only group did not differ from age-matched controls, but the SLI groups
      showed more limited ability to accurately identify words within sentences. Once
      this factor was taken into account, the groups did not differ in their ability to
      compensate for assimilation. The results add to a growing body of evidence that
      phonological representations are not necessarily impaired in dyslexia. SLI
      children's results suggest that they too are sensitive to this aspect of
      phonological grammar, but are more liberal in their acceptance of alternative
      phonological forms of words. Furthermore, these children's ability to reject
      alternative phonological forms seems to be primarily limited by their vocabulary
      size and phonological awareness abilities.

PMID- 21714756
TI  - Case series investigations in cognitive neuropsychology.
AB  - Case series methodology involves the systematic assessment of a sample of related
      patients, with the goal of understanding how and why they differ from one
      another. This method has become increasingly important in cognitive
      neuropsychology, which has long been identified with single-subject research. We
      review case series studies dealing with impaired semantic memory, reading, and
      language production and draw attention to the affinity of this methodology for
      testing theories that are expressed as computational models and for addressing
      questions about neuroanatomy. It is concluded that case series methods usefully
      complement single-subject techniques.

PMID- 21714757
TI  - Neural correlates of donepezil-induced cognitive improvement in patients with
      right hemisphere stroke: a pilot study.
AB  - Donepezil has been proven effective in the treatment of Alzheimer's disease and
      vascular dementia. However, its effects on the cognitive neural network have not
      been fully investigated. The purpose of this study was to evaluate the effect of
      donepezil on reorganisation of the cognitive neural network in patients with post
      stroke cognitive impairment using functional MRI (fMRI). Fourteen patients with
      stroke in the right hemisphere were enrolled. Participants were randomly assigned
      to the experimental or the control group. Donepezil (5 mg) or placebo was
      administered daily for four weeks. Cognitive function assessment was performed
      before and immediately after treatment, and repeated one month after cessation of
      treatment. fMRI was performed before and after treatment. Ten out of 14 patients
      (six in the experimental group, four in the control group) successfully completed
      all experimental processes. The experimental group showed significant
      improvements in the Mini-Mental Status Examination during the post-treatment
      evaluation and one-month follow-up compared to the pre-treatment evaluation (p <
      .05). No improvement was observed in the control group. In the experimental group
      fMRI showed increased activation in both prefrontal areas, both inferior frontal
      lobes, and in the left inferior parietal lobe. Increased recruitment of the
      parieto-frontal networks in the selected patients was considered to be a neural
      correlate of cognitive improvement induced by donepezil.

PMID- 21714758
TI  - Unrecognized hospital trauma as a source of complex psychiatric symptoms: a
      systematic case study with implications for children's rights and evidence-based
      practice.
AB  - This article describes the psychological assessment and treatment of Paul (12).
      For several years, he had received numerous diagnoses from a range of specialists
      and been unsuccessfully treated for epilepsy and obsessive-compulsive disorder.
      Treatment was based on a formulation-driven transdiagnostic approach. Soon it was
      clear that the correct diagnosis was posttraumatic stress disorder (PTSD)
      precipitated by an event in hospital when Paul was 6. Two sessions of Children's
      Accelerated Trauma Treatment (CATT) led to rapid resolution of the main symptoms
      and gains were consolidated and maintained in further treatment and follow-up
      sessions. The case material is used to examine why the correct case formulation
      had been missed, evidence for the efficacy of CATT, and implications for evidence
      based practice and children's rights.

PMID- 21714759
TI  - Therapists' and clients' experiences of alliance ruptures: a qualitative study.
AB  - AIM: We explored therapists' and clients' experiences of alliance rupture events
      for the first 15 sessions of each of eight cases; therapists were each paired
      with one client who had a personality disorder. METHOD: All sessions were
      videotaped and rated with the Rupture Resolution Rating System. Approximately 1
      week after a rupture, clients and therapists were individually interviewed about
      the causes of the rupture, how the rupture evolved, the impact of the rupture on
      the therapeutic process, and experiences during the event. The interviews were
      analyzed by five judges using consensual qualitative research (CQR; Hill, 2011).
      RESULTS: Typically, rupture events involved a repetition of a previous rupture
      event, the rupture emerged when the client was not prepared to respond to the
      therapist's intervention, both therapists and clients felt confused and
      ambivalent, and confrontation events activated intense and negative feelings. We
      discuss the implications for practice, training, and research.

PMID- 21714760
TI  - A paradigm for awake intraoperative memory mapping during forniceal stimulation.
AB  - A case report is presented detailing the successful use of awake intraoperative
      memory testing while using white matter stimulation in order to isolate the
      fornix tracks involved in memory function. The identification of the white matter
      tracks of the fornix that were involved in memory function was used to tailor the
      neurosurgical resection of a third ventricle tumor that was impinging on the
      fornix in order to successfully preserve memory functioning in the patient.

PMID- 21714761
TI  - Cooking "shrimp a la creole": a pilot study of an ecological rehabilitation in
      semantic dementia.
AB  - New learning in semantic dementia (SD) seems to be tied to a specific temporal
      and spatial context. Thus, cognitive rehabilitation could capitalise upon
      preserved episodic memory and focus on everyday activities which, once learned,
      will have an impact in everyday life. This pilot study thus explores the
      effectiveness of an ecological approach in one patient suffering from SD. EC, a
      68-year-old woman with SD, stopped cooking complex meals due to a substantial
      loss of knowledge related to all food types. The therapy consisted of preparing a
      target recipe. She was asked to generate semantic attributes of ingredients found
      in one target, one control and two no-therapy recipes. The number of recipes
      cooked by EC between therapy sessions was computed. She was also asked to prepare
      a generalisation recipe combining ingredients from the target and control
      recipes. EC's generated semantic attributes (GSA) of ingredients pertaining to
      the target and control recipes increased significantly (p < .001), compared to
      the no-therapy recipes (ps > .79). The proportion of meals cooked also increased
      significantly (p = .021). For the generalisation recipe, she could not succeed
      without assistance. Frequent food preparation may have provided EC with new
      memories about the context, usage and appearance of some concepts. These memories
      seem very context-bound, but EC nonetheless re-introduced some recipes into her
      day-to-day life. The impact of these results on the relationship between
      semantic, episodic and procedural memory is discussed, as well as the relevance
      of an ecological approach in SD.

PMID- 21714762
TI  - Essential oil composition of three species of Scutellaria from Turkey.
AB  - The chemical compositions of the essential oils obtained by hydrodistillation
      from the aerial parts of Scutellaria diffusa, Scutellaria heterophylla and
      Scutellaria salviifolia were separately identified simultaneously by gas
      chromatography and gas chromatography-mass spectrometry. The main components were
      determined as hexadecanoic acid (30%) and caryophyllene oxide (9%) in the oil of
      S. diffusa. Germacrene D (21%), hexadecanoic acid (16%) and beta-caryophyllene
      (13%) were found as major components in the oil of S. heterophylla. The main
      components of the oil of S. salviifolia were germacrene D (40%),
      bicyclogermacrene (14%) and beta-caryophyllene (11%). Overall, individually 63,
      68 and 43 constituents were identified in the aerial parts of S. diffusa, S.
      heterophylla and S. salviifolia essential oils representing 92.1%, 89.9% and 90%
      of the total, respectively.

PMID- 21714763
TI  - Synthesis of 1,2,4-triazole derivatives containing benzothiazoles as
      pharmacologically active molecule.
AB  - In attempt to make significant pharmacologically active molecule, we report here
      the synthesis and in vitro antimicrobial and antitubercular activity of various
      series of 3-(3-pyridyl)-5-(4-nitrophenyl)-4-(N-substituted-1,3-benzothiazol-2
      amino)-4H-1,2,4-triazole. The antimicrobial activity of title compounds were
      examined against two Gram-positive bacteria (Staphylococcus aureus, Streptococcus
      pyogenes), two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa),
      and three fungi (Candida albicans, Aspergillus niger, Aspergillus clavatus) using
      the broth microdilution method and antitubercular activity H(37)Rv using
      Lowenstein-Jensen agar method.

PMID- 21714764
TI  - Antimycobacterial activity: synthesis of novel 3-(substituted phenyl)-6,7
      dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues.
AB  - In this study, a series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4
      dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized and evaluated for
      antimycobacterial activity against Mycobacterium tuberculosis (MTB) H(37)Rv and
      isoniazid resistant M. tuberculosis (INHR-MTB). All the newly synthesized
      compounds were showing moderate to high inhibitory activities. The compound 6,7
      dimethoxy-3-(4-chloro phenyl)-4H-indeno[1,2-c]isoxazole (4b) was found to be the
      most promising compound, active against MTB H(37)Rv and INHR-MTB with minimum
      inhibitory concentrations of 0.22 and 0.34 MUM.

PMID- 21714766
TI  - MLL-SEPTIN gene fusions in hematological malignancies.
AB  - The mixed lineage leukemia (MLL) locus is involved in more than 60 different
      rearrangements with a remarkably diverse group of fusion partners in
      approximately 10% of human leukemias. MLL rearrangements include chromosomal
      translocations, gene internal duplications, chromosome 11q deletions or
      inversions and MLL gene insertions into other chromosomes, or vice versa. MLL
      fusion partners can be classified into four distinct categories: nuclear
      proteins, cytoplasmatic proteins, histone acetyltransferases and septins. Five
      different septin genes (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) have been
      identified as MLL fusion partners, giving rise to chimeric fusion proteins in
      which the N terminus of MLL is fused, in frame, to almost the entire open reading
      frame of the septin partner gene. The rearranged alleles result from
      heterogeneous breaks in distinct introns of both MLL and its septin fusion
      partner, originating distinct gene fusion variants. MLL-SEPTIN rearrangements
      have been repeatedly identified in de novo and therapy related myeloid neoplasia
      in both children and adults, and some clinicopathogenetic associations are being
      uncovered. The fundamental roles of septins in cytokinesis, membrane remodeling
      and compartmentalization can provide some clues on how abnormalities in the
      septin cytoskeleton and MLL deregulation could be involved in the pathogenesis of
      hematological malignancies.

PMID- 21714767
TI  - Postpartum hemorrhage in low risk population.
AB  - OBJECTIVE: To identify risk factors for postpartum hemorrhage (PPH) in low risk
      patients. METHODS: All deliveries between 2001 and 2007 were retrieved. Women
      with well-established preexisting risk factors for PPH were excluded. Among the
      remaining women (n=15,198) considered at low risk, various factors were assessed
      to evaluate their role in PPH. RESULTS: Rates of PPH increased from 1.03 in 2001
      to 2.45% in 2007. Gestational age at delivery, induction of labor with oxytocin,
      cesarean section and regional analgesia were not associated with PPH. Logistic
      regression analysis demonstrated that the following factors were significantly
      associated with PPH: increased birth weight (P<0.001), female gender (P=0.006),
      duration of membrane rupture (P=0.002), duration of second stage (P<0.001),
      chorioamnionitis (P=0.02), and use of prostaglandins (P=0.041). CONCLUSION: Early
      recognition of the specific factors presented as associated with PPH should
      prompt early intervention to reduce the PPH and maternal morbidity.

PMID- 21714768
TI  - Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and
      in human lymphocytes in vitro.
AB  - Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for
      the control of annual grasses in grain and vegetable crops. In this study, the
      genotoxic effects of DM were investigated by measuring chromosomal aberrations
      (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral
      lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125 mg/kg body weight
      of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250
      ug/mL concentrations were applied to human lymphocytes for both 24 and 48 hours.
      In in vivo treatments, DM significantly, but not dose dependently, increased the
      total chromosome aberrations, compared to both negative and solvent controls.
      Cell proliferation was significantly, but not dose dependently, affected by all
      doses. In in vitro treatments, DM (except 15.63 ug/mL) significantly and dose
      dependently increased the frequency of chromosome aberrations. Also, 250 ug/mL of
      48-hour treatment was found to be toxic. Cell proliferation was significantly and
      dose dependently affected by DM applications, when compared to negative control.
      In in vitro treatments, DM significantly decreased the mitotic index only at the
      highest concentration for 24 hours, and 62.5- and 125-ug/mL concentrations for 48
      hours. In the comet assay, a significant and dose-dependent increase in comet
      tail intensity was observed at 62.5-, 125-, and 250-ug/mL concentrations. The
      mean comet-tail length was significantly increased in all concentrations. Our
      results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.

PMID- 21714769
TI  - A 90-day safety study in Sprague-Dawley rats fed milk powder containing
      recombinant human lactoferrin (rhLF) derived from transgenic cloned cattle.
AB  - Transgenic cloned animals expressing beneficial human nutritional traits offer a
      new strategy for large-scale production of some kinds of functional substances.
      In some cases, the required safety testing for genetically modified (GM) foods do
      not seem appropriate for human food safety, though regulations do not seem to
      provide alternatives. A 90-day rat feeding study is the core study for the safety
      assessment of GM foods. The test material in this 90-day study was prepared
      nonfat milk powder containing recombinant human lactoferrin (rhLF), which was
      expressed in transgenic cloned cattle. Groups of 10 male and female Sprague
      Dawley rats were given a nutritionally balanced purified diet containing 7.5, 15,
      or 30% transgenic or conventional milk powder for 90 days. A commercial AIN93G
      diet was used as an additional control group. Clinical, biological, and
      pathological parameters were compared between groups. The only significant effect
      of treatment was higher mean ferritin and Fe(+) concentrations for both male and
      female rats fed the transgenic milk powder diets, as compared to rats fed
      nontransgenic milk diets or the commercial diet. The results of the present study
      are consistent with previous research, which indicates that milk powder
      containing rhLF derived from healthy transgenic cloned cattle is as safe as
      conventional milk powder.

PMID- 21714770
TI  - Cholestatic hepatitis related to amoxicillin.
AB  - While it is well recognized that the combination of amoxicillin and clavulanic
      acid has been associated with hepatic adverse events, there are only a few
      reports about amoxicillin alone causing hepatic toxicity. We describe a 34-year
      old woman who developed severe cholestatic hepatitis following amoxicillin
      treatment.

PMID- 21714771
TI  - Reproductive toxicity of di(2-ethylhexyl) phthalate in selenium-supplemented and
      selenium-deficient rats.
AB  - Phthalates are abundantly produced plasticizers, and di(ethylhexyl) phthalate
      (DEHP) is the most widely used derivative in various consumer products and
      medical devices. Animal studies show that DEHP and various other phthalates cause
      reproductive and developmental toxicity. Although the evidences are limited, it
      seems reasonable that DEHP may have a potential for similar adverse effects in
      humans. Such concerns are increasing, particularly for the developing
      reproductive system of male infants and children. By taking into account the
      essentiality of selenium (Se) in testicular structure and functions and the high
      prevalence of inadequate Se intake in various part of the world, this study was
      designed to investigate the testicular toxicity of DEHP in Se-deficient male rats
      and to examine the possible preventive effects of Se supplementation on phthalate
      toxicity. Se deficiency was generated by feeding 3-week-old Sprague-Dawley rats
      with a <=0.05 Se mg/kg diet for 5 weeks. Supplementation groups were on a 1 mg
      Se/kg diet, and DEHP-treated groups received a 1,000 mg/kg dose by gavage during
      the last 10 days of the feeding period. Testicular histopathology, sperm count
      and motility, and sperm morphology were examined, and plasma levels of sex
      hormones were measured. Toxicity and antiandrogenic effects of DEHP were
      evidenced by disturbed testicular histology and spermatogenesis, diminished
      testosterone, leutinizing hormone (LH) and follicle stimulating hormone (FSH)
      levels, and sperm motility. The effects of DEHP were much more pronounced in Se
      deficient rats, whereas Se supplementation was found to be protective, reflecting
      its regulating role in cellular redox equilibrium.

PMID- 21714772
TI  - Pro-oxidant and antiproliferative effects of the 1,3,4-thiadiazole-based Schiff
      base and its metal complexes.
AB  - Adverse biological activities of Schiff base (SB) derivatives are well known. In
      this study, the ligand and its metal complexes have been synthesized and
      characterized by IR, (1)H-NMR spectra, elemental analyses, magnetic
      susceptibility, UV-Vis spectra, and thermogravimetry/differential thermal
      analysis. From the elemental analyses data, the complexes were proposed to have
      the general formula [Mn(L)(2)(H(2)O)(2)], [Co(L)(2)(H(2)O)(2)], and
      [Ni(2)(L)(H(2)O)(4)(Cl)(3)]. From the magnetic moment and UV-Vis spectra data, it
      was found that the geometrical structures of these complexes are octahedral. In
      the in vivo experiment, adult male rats were injected subcutaneously with a new
      SB (L) and its [Mn(L)(2)(H(2)O)(2)], [Co(L)(2)(H(2)O)(2)], and
      [Ni(2)(L)(H(2)O)(4)(Cl)(3)] complexes (25 mg/kg body weight) and were then
      sacrificed 16 days later. Effects of these compounds on serum antioxidant
      vitamins (i.e., vitamins A, E, and C) and malondialdehyde (MDA) levels were
      measured in blood serum, liver, and kidney tissues. In an in vitro experiment,
      antiproliferative effects of these compounds were assessed on the human breast
      carcinoma MCF-7 and murine leukemia L1210 cell lines. Serum MDA and vitamins A,
      E, and C levels did not change by the treatments. However, in the kidney and
      liver tissues, MDA levels were higher, whereas vitamin levels were lower in
      treatment groups, compared to the control group. All compounds inhibited cell
      proliferation of MCF-7 and L1210 cancer cell lines in a dose- and time-dependent
      manner. In conclusion, SB derivatives tested in the current study induced
      oxidative stress in vivo and exhibited anti-proliferative effects in an in vitro
      culture system.

PMID- 21714773
TI  - Attenuating effect of lycopene and ellagic acid on 2,3,7,8-tetrachlorodibenzo-p
      dioxin-induced spermiotoxicity and testicular apoptosis.
AB  - This study was conducted to investigate the prophylactic effects of lycopene (LC)
      and ellagic acid (EA) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced
      testicular and spermatozoal toxicity. These toxicological changes are associated
      with the oxidative stress and apoptosis in male rats. Forty-eight male rats were
      allocated to one of six groups of 8 rats each: control, LC, EA, TCDD, TCDD+LC,
      and TCDD+EA. The control group was treated with 0.5 mL/rat slightly alkaline
      solution+0.5 mL/rat corn oil every other day. The LC group was treated with 0.5
      mL/rat slightly alkaline solution+0.5 mL/rat corn oil containing 10 mg/kg of LC
      every other day. The EA group received 0.5 mL/rat corn oil+0.5 mL/rat slightly
      alkaline solution containing 2 mg/kg of EA every other day. The TCDD group
      received 0.5 mL/rat corn oil containing 100 ng/kg/day of TCDD+0.5 mL/rat slightly
      alkaline solution. The TCDD+LC group was treated with 0.5 mL/rat TCDD+0.5 mL/rat
      LC. The TCDD+EA group was treated with 0.5 mL/rat TCDD+0.5 mL/rat EA. All
      treatments were made by gavage, and the experimental period was maintained during
      8 weeks. Sperm motility, concentration, and abnormal sperm rate in epididymal
      tissue, testicular tissue lipid peroxidation (LPO), antioxidant enzyme activity,
      histopathological changes, and apoptosis (i.e., Bax and Bcl-2 proteins) were
      determined. TCDD exposure resulted in significant decreases in sperm motility,
      concentration, testicular superoxide dismutase activity, germinal cell-layer
      thickness, Johnsen's testicular score, and significant increases in abnormal
      sperm rate, testicular malondialdehyde, glutathione levels, Bax-positive
      staining, and Bax-positive apoptotic cell score, along with some testicular
      histopathological lesions. TCDD treatment did not affect significantly catalase
      activity. However, combined treatment with LC or EA, in addition to TCDD,
      prevented the development of TCDD-induced damages in sperm quality, testicular
      histology, and LPO. Improvements in testicular apoptosis after the administration
      of LC and EA to TCDD-treated rats were minimal, but not statistically
      significant. TCDD-induced lipid peroxidation leads to functional and structural
      damages, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA
      protected against the development of these effects.

PMID- 21714774
TI  - Sexual offending and improvement in autistic characteristics after acquired brain
      injury: a case report.

PMID- 21714775
TI  - Why should psychiatrists learn about narrative therapy?

PMID- 21714776
TI  - Advances in drug delivery: Is triple therapy the future for the treatment of
      chronic obstructive pulmonary disease?
AB  - INTRODUCTION: Current therapies for chronic obstructive pulmonary disease (COPD)
      focus on the improvement of clinical symptoms via the use of bronchodilators:
      beta(2)-adrenoreceptor agonists and muscarinic (M3) acetylcholine receptor
      antagonists. The combination of inhaled corticosteroids (ICSs) and long-acting
      beta(2) agonists (LABAs), or LABAs and anticholinergics has become an efficient
      alternative to single therapies. These combinations consist of a LABA and an ICS
      together with an anticholinergic, such as ipratropium or tiotropium. AREAS
      COVERED: This review summarizes the latest thinking and findings on the
      usefulness of triple therapy in the treatment and management of COPD. Drawing on
      commercial, clinical, scientific and intellectual property data and publications,
      it aims to provide an overview to understand the efficacy and need for COPD
      triple therapy. The reader will gain an in-depth view of the triple therapy
      approach in managing COPD, existing molecules in the market or in development as
      well as new chemical entities. Clinical evidence in support of triple therapy,
      formulations and products are also discussed. EXPERT OPINION: There is limited
      documented clinical evidence for the use of triple therapy in COPD, reflected in
      the lack of commercial activity in the field. The future for the management of
      COPD may lie with triple therapy, but may equally rest on a better understanding
      of the disease and subsequent development of new chemical entities, such as dimer
      molecules, longer-acting beta-agonists and antimuscarinics.

PMID- 21714777
TI  - Pharmacological treatment of bowel obstruction in cancer patients.
AB  - INTRODUCTION: Malignant bowel obstruction (MBO) is a common complication of
      advanced cancer, occurring most frequently in gynaecological and colorectal
      cancer. Its management remains complex and variable. This is in part due to the
      lack of evidence-based guidelines for the clinicians involved. Although surgery
      should be considered the primary treatment, this may not be feasible in patients
      with a poor performance status or advanced disease. Advances have been made in
      the medical management of MBO which can lead to a considerable improvement in
      symptom management and overall quality of life. AREAS COVERED: This review
      emphasizes the importance of a prompt diagnosis of MBO with early introduction of
      pharmacological agents to optimize symptom control. The authors summarize the
      treatment options available for bowel obstruction in those patients for whom
      surgical intervention is not a feasible option. The authors also explore the
      complexities involved in the introduction of parenteral hydration and total
      parenteral nutrition in this group of patients. EXPERT OPINION: It is not always
      easy to distinguish reversible from irreversible bowel obstruction. Early and
      aggressive management with the introduction of pharmacological agents including
      corticosteroids, octreotide and anti-cholinergic agents have the potential to
      maintain bowel patency, and allow for more rapid recovery of bowel transit. A
      combination of analgesics, anti-emetics and anti-cholinergics with or without
      anti-secretory agents can successfully improve symptom control in patients with
      irreversible bowel obstruction.

PMID- 21714778
TI  - Longitudinal analysis of maternal risk factors for childhood sexual abuse: early
      attitudes and behaviours, socioeconomic status, and mental health.
AB  - OBJECTIVE: The objective of this study was to examine whether maternal factors
      such as socioeconomic status (SES), attitudes towards the baby, and mental health
      at 6 months or earlier, are associated with non-penetrative and penetrative
      childhood sexual abuse (CSA) in her offspring. METHODS: This was a prospective
      birth cohort study followed up to 21 years. Set in one of two obstetric hospitals
      in Brisbane, Australia, the Mater-University of Queensland Study of Pregnancy
      (MUSP) involves a prospective birth cohort from a population based sample of 7223
      singletons whose mothers were enrolled between 1981 and 1984 at the first
      antenatal visit. The present cohort consisted of 2664 participants who provided
      CSA data, and whose mothers had responded to all relevant questions. RESULTS:
      About 16% of young adults reported non-penetrative sexual abuse before the age of
      sixteen and 9% reported penetrative abuse. After adjusting for all variables in
      the model, an increased risk for non-penetrative CSA was associated with the
      child being female, unwanted pregnancy, mother being a heavy smoker, and maternal
      anxiety. Increased risk for penetrative CSA was associated with the child being
      female, the mother having failed to complete a high school level education,
      living in an alternative arrangement other than marriage, and being either a
      moderate or heavy smoker. We found no associations between maternal age and CSA
      after correcting for other predictors. CONCLUSION: CSA was not uncommon in this
      cohort with one in four reporting some form of sexual abuse before 16. The
      results suggest that several early factors may predict later CSA and that the
      associations are different according to type of CSA.

PMID- 21714779
TI  - Colonization of citrus seed coats by 'Candidatus Liberibacter asiaticus':
      implications for seed transmission of the bacterium.
AB  - Huanglongbing is an economically damaging disease of citrus associated with
      infection by 'Candidatus Liberibacter asiaticus'. Transmission of the organism
      via infection of seeds has not been demonstrated but is a concern since some
      citrus varieties, particularly those used as rootstocks in commercial plantings
      are propagated from seed. We compared the incidence of detection of 'Ca.
      Liberibacter asiaticus' DNA in individual fruit peduncles, seed coats, seeds, and
      in germinated seedlings from 'Sanguenelli' sweet orange and 'Conners' grapefruit
      fruits sampled from infected trees. Using real-time quantitative PCR (qPCR) we
      detected pathogen DNA in nucleic acid extracts of 36 and 100% of peduncles from
      'Sanguenelli' and from 'Conners' fruits, respectively. We also detected pathogen
      DNA in extracts of 37 and 98% of seed coats and in 1.6 and 4% of extracts from
      the corresponding seeds of 'Sanguenelli' and 'Conners', respectively. Small
      amounts of pathogen DNA were detected in 10% of 'Sanguenelli' seedlings grown in
      the greenhouse, but in none of 204 extracts from 'Conners' seedlings. Pathogen
      DNA was detected in 4.9% and in 89% of seed coats peeled from seeds of
      'Sanguenelli' and 'Conners' which were germinated on agar, and in 5% of
      'Sanguenelli' but in none of 164 'Conners' seedlings which grew from these seeds
      on agar. No pathogen DNA was detected in 'Ridge Pineapple' tissue at 3 months
      post-grafting onto 'Sanguenelli' seedlings, even when pathogen DNA had been
      detected initially in the 'Sanguenelli' seedling. Though the apparent
      colonization of 'Conners' seeds was more extensive and nearly uniform compared
      with 'Sanguenelli' seeds, no pathogen DNA was detected in 'Conners' seedlings
      grown from these seeds. For either variety, no association was established
      between the presence of pathogen DNA in fruit peduncles and seed coats and in
      seedlings.

PMID- 21714780
TI  - Bayesian enrichment strategies for randomized discontinuation trials.
AB  - We propose optimal choice of the design parameters for random discontinuation
      designs (RDD) using a Bayesian decision-theoretic approach. We consider
      applications of RDDs to oncology phase II studies evaluating activity of
      cytostatic agents. The design consists of two stages. The preliminary open-label
      stage treats all patients with the new agent and identifies a possibly sensitive
      subpopulation. The subsequent second stage randomizes, treats, follows, and
      compares outcomes among patients in the identified subgroup, with randomization
      to either the new or a control treatment. Several tuning parameters characterize
      the design: the number of patients in the trial, the duration of the preliminary
      stage, and the duration of follow-up after randomization. We define a probability
      model for tumor growth, specify a suitable utility function, and develop a
      computational procedure for selecting the optimal tuning parameters.

PMID- 21714781
TI  - Discussion of the article by Trippa, Rosner, and Muller on Bayesian enrichment
      strategies for randomized discontinuation trials.
AB  - We congratulate Trippa, Rosner, and Muller (2011, Biometrics, in press) on an
      intriguing and timely article. The randomized discontinuation design (RDD) has
      only recently been used in cancer clinical trials, and methodological
      understanding on how to best design such studies is limited. The authors'
      approach to optimize RDD designs based on prior information and utility
      considerations is an important step forward. A noteworthy element is their use of
      a semimechanistic model to describe tumor growth. Mathematical models have
      provided considerable insight on the complex process of tumor evolution
      (Preziosi, 2003, Cancer Modelling and Simulation). Utilizing this knowledge
      should lead to better design, analysis, and decisions.

PMID- 21714782
TI  - Optimal Bayesian enrichment: a view from the closet.

PMID- 21714783
TI  - Discussion: "Bayesian enrichment strategies for randomized discontinuation
      trials".

PMID- 21714784
TI  - Discussion of Trippa, Rosner, and Muller--Bayesian enrichment strategies for
      randomized discontinuation trials.

PMID- 21714787
TI  - Reduced size and starvation resistance in adult mosquitoes, Aedes notoscriptus,
      exposed to predation cues as larvae.
AB  - 1. Many prey organisms exhibit adaptive phenotypic plasticity in life-history
      traits that facilitate a better chance of survival in the presence of predators.
      The evolution of such plastic traits requires that the defensive phenotype incurs
      a cost in the absence of predation. 2. Model systems that are used to examine
      predator-induced defences are often organisms with complex life histories that
      only induce defences during the larval stage. While many studies have detected
      costs of inducible defences during the larval stage, detecting the costs of
      larval defences after metamorphosis is also important. 3. We examine the benefits
      and costs of inducible larval defences in the urban mosquito, Aedes notoscriptus,
      by rearing them in the presence and absence of predation cues. We compared
      survival of larvae inducing behavioural defences, when exposed to predation cues,
      in predation trials with predatory fish Hypseleotris galii to that of larvae
      reared in the absence predation cues. We also compared life-history traits of
      predator-exposed larvae to larvae reared in control conditions. 4. Larvae exposed
      to chemical predation cues limited activity and were able to avoid predation for
      longer in trials with H. galii. However, predator-exposed larvae suffered
      retarded larval growth and development, were smaller at metamorphosis and less
      resistant to starvation as adults. 5. While it is difficult to understand the
      'fitness costs' that poorer starvation resistance might confer to adult
      mosquitoes, it is likely that smaller adult size of predator-exposed individuals
      would reduce fitness, particularly for females where body size limits the size of
      blood meal they could take to facilitate egg production. We suggest that the
      demonstrable costs of inducible defences in mosquito larvae make this a good
      system for testing theoretical models for the evolutionary maintenance of
      adaptive phenotypic plasticity.

PMID- 21714788
TI  - Broadening the study of phenology and climate change.

PMID- 21714789
TI  - Peatlands in a changing world.

PMID- 21714790
TI  - Composition and diversity of nifH genes of nitrogen-fixing cyanobacteria
      associated with boreal forest feather mosses.
AB  - Recent studies have revealed that nitrogen fixation by cyanobacteria living in
      association with feather mosses is a major input of nitrogen to boreal forests.
      We characterized the community composition and diversity of cyanobacterial nifH
      phylotypes associated with each of two feather moss species (Pleurozium schreberi
      and Hylocomium splendens) on each of 30 lake islands varying in ecosystem
      properties in northern Sweden. Nitrogen fixation was measured using acetylene
      reduction, and nifH sequences were amplified using general and cyanobacterial
      selective primers, separated and analyzed using density gradient gel
      electrophoresis (DGGE) or cloning, and further sequenced for phylogenetic
      analyses. Analyses of DGGE fingerprinting patterns revealed two host-specific
      clusters (one for each moss species), and sequence analysis showed five clusters
      of nifH phylotypes originating from heterocystous cyanobacteria. For H. splendens
      only, N(2) fixation was related to both nifH composition and diversity among
      islands. We demonstrated that the cyanobacterial communities associated with
      feather mosses show a high degree of host specificity. However, phylotype
      composition and diversity, and nitrogen fixation, did not differ among groups of
      islands that varied greatly in their availability of resources. These results
      suggest that moss species identity, but not extrinsic environmental conditions,
      serves as the primary determinant of nitrogen-fixing cyanobacterial communities
      that inhabit mosses.

PMID- 21714791
TI  - Ablation of epicardial right ventricular tachycardia provoked by proarrhythmic RV
      pacing in a patient with dilated cardiomyopathy.
AB  - Ventricular arrhythmias are common in the setting of nonischemic dilated
      cardiomyopathy (NIDCM). However, the characterization of the substrate and
      mechanism of epicardial ventricular tachycardia (VT) associated with NIDCM is
      limited, and to the best of our knowledge VT due to myocardial reentry within the
      right ventricular (RV) epicardium associated with NIDCM has not been reported. We
      report a case of RV epicardial VT provoked by RV pacing that was successfully
      ablated.

PMID- 21714792
TI  - The hemodynamic effect of right ventricle (RV), RT3DE targeted left ventricle
      (LV) and biventricular (BIV) pacing in the early postoperative period after
      cardiac surgery.
AB  - BACKGROUND: Congestive heart failure negatively impacts the prognosis in patients
      after cardiac surgery. The aim of our study was to assess the value of targeted
      cardiac resynchronization therapy (CRT) within 72 hours after cardiac surgery in
      patients with mechanical dyssynchrony, who had an ejection fraction <= 35%, QRS
      >=150 ms or between 120 and 150 ms. METHODS: A prospective randomized trial based
      on three-dimensional echocardiography (RT3DE) and optimized sequential dual
      chamber (DDD ) pacing in patients after cardiac surgery. DDD epicardial pacing
      (Medtronic coaxial epicardial leads 6495) was provided by a modified Medtronic
      INSYNC III Pacemaker (Medtronic Inc., Minneapolis, MN, USA). SUMMARY OF RESULTS:
      The study included 21 patients with ischemic heart disease (HD) or valvular HD
      (16 men, 5 women, average age 69 years) with left ventricle (LV) dysfunction
      after cardiac surgery . Patients with biventricular (BIV) (CO 6.7 +/- 1.7 L/min,
      CI 3.5 +/- 0.8 L/min/m(2) ) and LV (CO 6.2 +/- 1.5 L/min, CI 3.2 +/- 0.7
      L/min/m(2) ) pacing had statistically significantly higher CO and CI than
      patients with right ventricular (RV) (CO 5.4 +/- 1.4 L/min, CI 2.8 +/- 0.6
      L/min/m(2) ) pacing (BIV vs RV P <= 0.001; LV vs RV P <= 0.05; BIV vs LV P <=
      0.05). CONCLUSIONS: RT3DE targeted and optimized CRT in the early postperative
      period after cardiac surgery provided better hemodynamic results than RV pacing. 

PMID- 21714793
TI  - Multilevel population genetics in antibiotic resistance.

PMID- 21714794
TI  - Development of a refractory gastro-oesophageal reflux score using an
      administrative claims database.
AB  - BACKGROUND: Approximately one-third of gastro-oesophageal reflux disease (GERD)
      patients demonstrate refractory symptoms following treatment with proton pump
      inhibitor (PPI) therapy. AIM: To develop a refractory GERD score that can be
      applied to predict patients' healthcare utilisation. METHODS: We enrolled adults
      (>=18 years) with a diagnosis of GERD. Refractory GERD was evaluated on an 8
      point scale where 1 point was given for each of the following criteria: doubling,
      addition, or switching of GERD medication dose, receipt of a GERD-related
      endoscopic procedure or surgery, or >=3 GERD-related outpatient visits.
      Refractory GERD was defined as the presence of two or more points. RESULTS: A
      total of 135,139 GERD patients (44% male) were analysed with a mean (+/-s.d.) age
      of 52.9 +/- 15 years. The mean overall refractory GERD score was 1.12 +/- 1.2
      (range 0-8 on an 8-point scale); 31% of patients had refractory GERD with a mean
      score of 2.56 +/- 0.82. Among patients with refractory GERD, 31% doubled their
      GERD medication, 28% added a new GERD medication, 60% switched GERD medications,
      54% had a GERD-related procedure and 1% had a GERD-related surgery. Patients with
      refractory GERD were more likely to be female (59% vs. 55%, P < 0.001) and had a
      higher co-morbidity score (0.78 vs. 0.56, P < 0.001). The overall mean costs for
      refractory patients during the study period were significantly higher compared
      with treatment-responsive patients ($18,088 +/- $36,220 vs. $11,044 +/- $22,955,
      P < 0.001). CONCLUSIONS: Refractory GERD was present in approximately one-third
      of the GERD patients. We created a GERD refractory score that could define need
      for increased anti-reflux therapy and predict higher healthcare resource
      utilisation.

PMID- 21714795
TI  - Nephrotoxicity, including acquired Fanconi's syndrome, caused by adefovir
      dipivoxil - is there a safe dose?
AB  - WHAT IS KNOWN AND OBJECTIVE: Adefovir dipivoxil (ADV) is an oral bioavailable
      prodrug of adefovir that possesses potent in vitro activity against
      hepadnaviruses, retroviruses and herpes viruses. ADV is excreted unchanged in the
      urine through glomerular filtration and tubular secretion and is known to be
      nephrotoxic at doses of 60mg daily and above. Thus, the long-term safety of ADV,
      particularly nephrotoxicity, is a major concern. Our objective is to comment on
      the nephrotoxcicity of low-dose (10mg daily) ADV through a case report. COMMENT:
      The clinical features of nephrotoxicity because of ADV are described. A case
      report of acquired Fanconi's syndrome in a chronic hepatitis B patient treated
      with ADV 10mg daily is used to illustrate several key aspects. WHAT IS NEW AND
      CONCLUSION: Adefovir dipivoxil can be nephrotoxic at conventional dosage and
      therefore, patients treated with long-term ADV should have regular monitoring of
      renal function, and calcium and phosphate levels.

PMID- 21714796
TI  - Effect of dehydroleucodine on the reproductive tract of male mice.
AB  - The effects of a sesquiterpene lactone, dehydroleucodine, on the reproductive
      tract were investigated using adult male mice. Dehydroleucodine was dissolved in
      tap water and administered as drinking water for 30 days. All the parameters were
      compared with a control group that received only vehicle. Animals were killed by
      decapitation and the trunk blood, the testes and the epididymes were collected.
      Plasma concentrations of testosterone and oestradiol, and testicular weight and
      concentration of spermatids did not change by dehydroleucodine. Nevertheless, in
      epididymal cauda dehydroleucodine treatment caused a diminution in sperm number,
      a decrease in the amount of tubular fluid and a reduction in the activity of the
      hydrolytic enzyme N-acetyl-beta-d-glucosaminidase. However, the sperm motility
      was not altered by dehydroleucodine treatment, although sperm binding to zona
      free oocytes increased significantly. These results suggest that
      dehydroleucodine, which has been implicated in the inhibition of aromatase P450,
      does not affect the plasma concentration of testosterone and oestradiol or
      testicular activity, whereas altering several epididymal parameters. The
      epididymis is thus a more sensitive target for dehydroleucodine action.

PMID- 21714797
TI  - Validation of reference genes in human testis and ejaculate.
AB  - Beta-actin (ACTB), glyceraldehyde-3-phosphate-dehydrogenase (GAPD), Heat Shock
      Protein 1, beta (HSPCB) and Adenosine Triphosphate subunit 5 beta (ATP5B) with
      distinct functional characteristics and expression patterns were investigated as
      suitable references for gene expression studies. We determined the expression
      stability of the four reference genes in ejaculates, cryopreserved as well as
      fixed and paraffin-embedded testicular tissue (from fertile and subfertile men)
      applying real-time qRT-PCR and statistical analysis. The mean gene expressions
      (mean Ct value) were compared for each gene between the fertile and subfertile
      donors by using the Wilcoxon-Mann-Whitney test. We did not observe significant
      statistical differences between variability of genes. To detect random effects,
      we used the two-way analysis of variance with a hierarchical model. The results
      show no significant statistical differences between proband and repetition within
      the probands. Taken together, we concluded that ACTB, GAPD, HSPCB and ATP5B have
      a variable expression within these samples, but this variability is not
      statistically significant. This finding demonstrated that all these genes could
      be appropriated for further studies on gene expression in ejaculate and testis
      tissue. Therefore, the selection of the suitable reference genes is highly
      specific for a particular experimental model and validation for each situation,
      on an individual basis, is a crucial requirement.

PMID- 21714798
TI  - Modified microsurgical subinguinal varicocelectomy without testicular delivery.
AB  - The aim of this study is to report our experience of modified microsurgical
      subinguinal varicocelectomy without delivery of the testes. We retrospectively
      evaluated 138 men treated with microsurgical varicocelectomy who took part in 1
      year follow-up between 1997 and 2007. The varicoceles were grade III in 115
      (81.6%), grade II in 23 (16.3%), and grade I in 3 (2.1%) men. We used a technical
      modification of the standard microsurgical subinguinal technique: division of the
      spermatic cord before microsurgical dissection, and the testes were not
      delivered. Patient age, varicocele grade, operation time, 1-year follow-up
      results, including complications, symptom relief, and recurrence, were recorded.
      We performed 141 varicocelectomies (Left: n = 135; bilateral: n = 3) in 138 men.
      The patients' mean age was 23.5 +/- 2.7 (range: 11-45) years. The mean operation
      time was 69.6 +/- 15.6 (range: 35-140) min. There were three complications (2.2%;
      post-operative haematomas: n = 2; wound infection: n = 1) and 6 recurrences
      (4.3%; grade II: n = 1; grade III: n = 5). Among the 86 patients with scrotal
      pain, 74 (77.9%) reported complete resolution of pain and 13 (12.9%) reported
      partial resolution. Modified microsurgical subinguinal varicocelectomy without
      testis delivery is safe and effective.

PMID- 21714799
TI  - Effect of nicotine on spermatogenesis in adult albino rats.
AB  - This study aimed to assess the effects of nicotine on spermatogenesis in 140
      mature male albino rats divided into group A (controls), group B (sham controls),
      group C (nicotine treated) and group D (nicotine withdrawal). Group C was
      subdivided into CI, CII, CIII according to the dose of injected nicotine (0.2,
      0.4 and 0.6 mg nicotine per 100 g per day), where each subgroup was further
      subdivided according to the treatment duration into subgroups a, b and c that
      received nicotine for 2, 4 and 8 weeks. Group D received nicotine for 8 weeks
      followed by withdrawal for another 8 weeks to assess testicular recovery.
      Testicular tissue sections were subjected to haematoxylin and eosin, Masson's
      trichrome stains and morphometry. The results showed that nicotine caused
      degenerative changes in the seminiferous tubules, revealed by altered general
      tubular architecture, decreased thickness of the spermatogenic cell masses,
      Sertoli cell vacuolation and thickened basal lamina. These changes were
      proportional to the nicotine dose and duration. Following nicotine withdrawal,
      regeneration of the damaged seminiferous tubules was observed to be rather
      complete in CI group. It is concluded that nicotine could adversely affect
      testicular spermatogenesis in a dose- and time-dependent manner which would be
      almost reversible after nicotine withdrawal, especially after small doses.

PMID- 21714800
TI  - Re-evaluation of post-wash sperm is a helpful tool in the decision to perform in
      vitro fertilisation or intracytoplasmic sperm injection.
AB  - The aim of this study was to find discriminatory parameters, based on sperm
      characteristics on the day of ovum pickup, that can help guide the decision to
      perform either intracytoplasmic sperm injection (ICSI) or in vitro fertilisation
      (IVF). We evaluated 112 cycles fertilised with both regular and ICSI insemination
      during the same cycle. A total of 112 cycles were analysed. In 62 cycles,
      fertilisation was obtained with both ICSI and IVF, and in 50 cycles,
      fertilisation was obtained by ICSI alone. The sperm samples were re-evaluated
      after the preparation process. The mean initial total motile sperm count (TMSC)
      was 66.3 * 10(6) +/- 47.5 in the group that underwent both methods and 23.1 *
      10(6) +/- 20.4 in the ICSI only group (P < 0.05). After sperm preparation, the
      mean post-wash TMSC was 4.4 * 10(6) +/- 3.4 and 1.06 * 10(6) +/- 0.9 respectively
      (P < 0.05). A cutoff of 1.5 * 10(6) or fewer sperm after preparation as an
      indicator for ICSI has a sensitivity of 80% and a specificity of 77%. Re
      evaluation of TMSC can prevent unexpected fertilisation failure. Fewer than 1.5
      million TMSC after wash should be considered an indication for ICSI
      fertilisation.

PMID- 21714801
TI  - Study of aneuploidy rate and sperm DNA fragmentation in large-headed, multiple
      tailed spermatozoa.
AB  - The aim of this study was to analyse the meiotic segregation and DNA
      fragmentation rates in ejaculated spermatozoa of Tunisian men who presented the
      macrocephalic sperm head syndrome and to compare the results with those from 20
      fertile men with normal semen profiles. Sperm DNA fragmentation was evaluated by
      the terminal desoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      biotin nick-end labelling assay. Fluorescence in situ hybridisation for
      chromosomes X, Y and 18 was performed for the study of meiotic segregation.
      Despite a normal blood karyotype, patients with large-headed spermatozoa showed a
      significantly higher incidence of sperm chromosomal abnormalities compared with
      the control group. For all the patients, tetraploidy, triploidy and diploidy were
      the most observed abnormalities. A very high level of DNA fragmentation was shown
      for these patients. In conclusion, our results demonstrated that patients with
      large-headed, multiple-tailed spermatozoa had significantly higher incidence of
      sperm chromosomal abnormalities and very high level of DNA fragmentation. So
      intracytoplasmic sperm injection should not be recommended to these patients, not
      only because of its low chances of success rate but also because of its high
      genetic risk.

PMID- 21714802
TI  - Influence of mitochondrial membrane potential of spermatozoa on in vitro
      fertilisation outcome.
AB  - To determine whether the outcome of in vitro fertilisation (IVF) is influenced by
      the percentage of spermatozoa with functional mitochondria, a total of 91 random
      couples undergoing IVF were included. Mitochondrial function was determined by
      flow cytometry and expressed as percentage of spermatozoa. Conventional sperm
      parameters were studied by light microscopy. Reproductive outcome parameters were
      fertilisation rate, embryo quality and clinical pregnancy. It was found that the
      fertilisation rate was correlated with the percentage of spermatozoa (r = 0.24, P
      = 0.01) as well as with the percentage of highly motile spermatozoa. However, we
      did not find any relationship between the percentage of spermatozoa and embryo
      quality. Nevertheless, no patient who exhibited less than 64% of spermatozoa
      achieved pregnancy. It is concluded that determination of Deltapsi(m) provides
      accurate information to guide physicians to identify male patients for whom IVF
      will be unlikely to result in pregnancy. Therefore, we suggest that the
      percentage of spermatozoa may contribute to identify the most appropriate
      treatment for an individual patient.

PMID- 21714803
TI  - Segmental testicular infarction.
AB  - We report a case of segmental testicular infarction occurring in a 24-year-old
      African Malian man who presented with a complaint of sudden and severe left
      testicular pain for 4 days. Scrotal ultrasound showed a hypoechoic mass in the
      left testicle. The hypoechoic area demonstrated no blood flow in colour Doppler
      mode. The patient underwent a left testicular exploration. A partial orchiectomy
      was performed with complete excision of the lesion. Pathological evaluation
      revealed a segmental testicular haemorrhagic infarction.

PMID- 21714804
TI  - Androgen receptor-CAG repeats in infertile Egyptian men.
AB  - This study aimed to assess the androgen receptor (AR) codon amino acids glutamine
      (CAG) repeats in 185 Egyptian men divided into fertile controls (n = 30),
      oligoasthenoteratozoospermic (OAT) men (n = 35), nonobstructive azoospermic (NOA)
      men (n = 120; 18 successful testicular sperm extraction (TESE) and 102
      unsuccessful TESE cases). They were subjected to history taking, genital
      examination, semen analysis, testicular biopsies for NOA cases, serum hormones
      and CAG repeats by PCR. The mean AR-CAG repeats showed significant difference
      between NOA group compared with fertile controls or OAT groups. Nonsignificant
      difference was elicited between OAT group and fertile controls. In NOA cases, CAG
      repeats demonstrated nonsignificant difference between unsuccessful and
      successful TESE. AR-CAG repeats elicited significant negative correlation with
      sperm count, significant positive correlation with sperm normal forms percentage
      and nonsignificant correlations with sperm motility per cent, tested serum
      hormones or testicular volume. It is concluded that AR-CAG repeats in Egyptian
      infertile men are in the range of other international or regional studies. AR-CAG
      repeats have demonstrated nonsignificant difference regarding TESE outcome in NOA
      cases.

PMID- 21714805
TI  - A red palm oil diet can reduce the effects of oxidative stress on rat
      spermatozoa.
AB  - Male Wistar rats (n = 54) received daily supplementation of red palm oil (RPO: 0,
      2, 4 ml). Subgroups were subsequently injected with saline, cumene hydroperoxide
      (cHP, 10 MUm) or t-butyl hydroperoxide (tbHP, 20 MUm) over a 60-day period after
      which animals were sacrificed. Epididymal sperm motility, concentration, reactive
      oxygen species (ROS), lipid peroxidation and enzymes were measured. Sperm
      concentration, motility, superoxide dismutase (SOD) concentration, glutathione
      (GSH) and catalase (CAT) activities were significantly lower, while
      dichlorofluorescein (DCF) and malondialdehyde (MDA) were higher in sperm of
      hydroperoxide-treated animals compared to controls (P < 0.05). DCF and MDA levels
      were significantly lower, while SOD, CAT and GSH were significantly higher in the
      sperm of rats supplemented with RPO in combination with hydroperoxide treatment
      when compared to those receiving hydroperoxide and no RPO supplementation (P <
      0.05). Moreover, the DCF, SOD, CAT and GSH levels in the RPO hydroperoxide groups
      did not differ from control values (P > 0.05). RPO supplementation can
      successfully attenuate the oxidative stress-induced sperm damage due to organic
      hydroperoxide exposure. We therefore propose that a daily intake of RPO
      supplement to the diet might be helpful in protecting males against the adverse
      effects of high ROS in sperm function and help preserve fertility.

PMID- 21714806
TI  - Evaluation of serum oxidative and antioxidative status in patients with erectile
      dysfunction.
AB  - We evaluated and compared serum oxidative and antioxidative parameters of
      patients with erectile dysfunction (ED) and control subjects. Twenty married male
      patients with ED for at least 12 months (Group 1) and 20 volunteer healthy,
      sexually active, married and age-matched men (Group 2) were included in the
      study. Group 1 and 2 were compared concerning serum mean total antioxidant
      capacity (TAC), total oxidant status (TOS), paraoxonase1 (PON1), arylesterase,
      total thiol and oxidative stress index (OSI). Mean patient age was 47.9 +/- 8.1
      and 44.4 +/- 10.6, respectively, in Group 1 and 2. Serum TAC levels were 1.7 +/-
      0.5 and 2.3 +/- 0.3, respectively, in Group 1 and 2 (P = 0.002). Serum TOS levels
      were 21.8 +/- 20.5 and 11.7 +/- 2.2, respectively, in Group 1 and 2 (P = 0.035).
      Serum PON1 levels were 69.8 +/- 13.1 and 164.9 +/- 56.5, respectively, in Group 1
      and 2 (P < 0.001). Serum arylesterase levels were 336 +/- 12 and 370.4 +/- 47.9,
      respectively, in Group 1 and 2 (P = 0.003). Serum total thiol levels were 733.1
      +/- 253 and 885.5 +/- 95.3, respectively, in Group 1 and 2 (P = 0.016). Serum OSI
      was 0.14 +/- 0.17 and 0.05 +/- 0.11, respectively, in Group 1 and 2 (P = 0.021).
      Mean blood platelet count was significantly higher in Group 1 (P = 0.001). A
      positive correlation between platelets and oxidative state and a negative
      correlation between platelets and antioxidative state were found. Oxidative
      stress was detected to be increased, whereas antioxidative parameters were
      detected to be decreased in patients with ED.

PMID- 21714807
TI  - Physicians' reported needs of drug information at point of care in Sweden.
AB  - AIMS: Relevant and easily accessible drug information at point-of-care is
      essential for physicians' decision making when prescribing. However, the
      information available by using Clinical Decision Support Systems (CDSSs) often
      does not meet physicians' requirements. The Summary of Product Characteristics
      (SmPC) is statutory information about drugs. However, the current structure,
      content and format of SmPCs make it difficult to incorporate them into CDSSs and
      link them to relevant patient information from the Electronic Health Records. The
      aim of the study was to evaluate the perceived needs for drug information among
      physicians in Sweden. METHODS: We recruited three focus group discussions with 18
      physicians covering different specialities. The information from the groups was
      combined with a questionnaire administered at the beginning of the group
      discussions. RESULTS: Physicians reported their needs for knowledge databases at
      the point of drug prescribing. This included more consistent information about
      existing and new drugs. They also wished to receive automatically generated
      alerts for severe drug-drug interactions and adverse effects, and to have
      functions for calculating glomerular filtration rate to enable appropriate dose
      adjustments to be made for elderly patients and those with impaired renal
      function. Additionally, features enhancing electronic communication with
      colleagues and making drug information more searchable were suggested.
      CONCLUSIONS: The results from the current study showed the need for knowledge
      databases which provide consistent information about new and existing drugs. Most
      of the required information from physicians appeared to be possible to transfer
      from current SmPCs to CDSSs. However, inconsistencies in the SmPC information
      have to be reduced to enhance their utility.

PMID- 21714808
TI  - Rosacea fulminans in pregnancy: successful treatment with azithromycin.

PMID- 21714809
TI  - A case of widespread hypertrophic scarring in a child after chickenpox.

PMID- 21714810
TI  - An approach to comparative anatomy of the acetabulum from amphibians to primates.
AB  - The objective of this study was to investigate the anatomy, both macroscopic and
      microscopic, of the soft tissue internal structures of the hip joint in animal
      species and in three human hips (an adult and two fetuses). We dissected the hip
      joints of 16 species and compared the anatomical features of the soft tissue from
      the respective acetabula. In addition, a histological study was made of the
      specimens studied. In amphibians, we found a meniscus in the acetabulum, which
      was not observed in any of the other species studied. The isolated round ligament
      is observed from birds onwards. In the group of mammals analysed, including the
      human specimens, we found a meniscoid structure in the acetabular hip joint.
      Furthermore, we found that the meniscoid structure forms an anatomo-functional
      unit with the round ligament and the transverse ligament of the coxofemoral
      joint. These discoveries suggest the participation of the soft tissue anatomy in
      adaptative changes of species.

PMID- 21714811
TI  - Expression of oestrogen receptors in foetal lung tissue of mice.
AB  - Oestrogens are responsible for the sexual dimorphism in adult mice lung tissue,
      and this difference is most notable at sexual maturity. Oestrogen receptor-alpha
      (ERalpha) and the oestrogen receptor-beta (ERbeta) are the two receptors that
      mediate oestrogen action, but adult mice lung tissue only expresses ERbeta, and
      it is probably through this receptor that oestrogens exert their action. The goal
      of our study was to detect the expression of ERalpha and ERbeta in mouse foetal
      lung tissues and identify possible gender differences. The foetal lung tissue was
      collected between developmental days E15-E19, processed for histology and the
      expression of oestrogen receptors was detected by immunohistochemistry. Over the
      5 days of lung development that were evaluated ERalpha was not expressed in the
      foetal lung tissues of neither male nor female mice. In contrast, ERbeta was
      detected in both sexes, although the immunoreactivity differed for each
      developmental day whilst the staining intensity observed for ERbeta also
      indicated differences between male and female lung tissues. The results
      demonstrate the existence of a gender difference in the foetal expression of
      ERbeta in lungs of mice.

PMID- 21714812
TI  - Nosology and therapeutic options for lupus miliaris disseminatus faciei.
AB  - Lupus miliaris disseminatus faciei (LMDF) is a distinctive facial eruption of a
      debatable nosology, unknown etiology and spontaneously resolving course albeit
      with scarring. The aim of this study was to present the clinico-histopathological
      features, the rationale for treating and therapeutic response in patients with
      LMDF treated with different agents, and to attempt to clarify its nosology.
      Clinical details and demographic data of 29 biopsy-proven cases of LMDF were
      studied. Laboratory work up included complete blood count, erythrocyte
      sedimentation rate, tuberculin testing, chest X-ray, serum calcium levels and
      serum angiotensin-converting enzyme levels. Special stains like Ziehl-Neelsen,
      periodic acid Schiff and reticulin staining were used, and acid-fast bacilli
      culture was performed in each patient. The patients were treated with oral
      minocycline, dapsone, prednisolone and isotretinoin as monotherapeutic agents, or
      with a combination of oral dapsone plus prednisolone, and oral dapsone plus
      topical tacrolimus. Six patients had extrafacial lesions. Histological analysis
      revealed three different patterns: tuberculoid granuloma with central caseation
      necrosis in 20 patients; sarcoidal-like granuloma in six patients; and non
      specific localized perifollicular lymphohistiocytic infiltrate in three patients.
      Nine out of 11 patients treated with minocycline did not respond, whereas dapsone
      and low dose prednisone alone or in combination produced good results. Topical
      tacrolimus with dapsone in seven patients yielded excellent results. Early and
      judicious use of medicines can clear this condition without scarring. LMDF should
      be accepted as a distinct entity. Facial idiopathic granulomas with regressive
      evolution (FIGURE), an acronym suggested is an apt, self-explanatory and easy
      term for LMDF, with no connotation of tubercular etiology.

PMID- 21714813
TI  - Connexin26 expression in brain parenchymal cells demonstrated by targeted
      connexin ablation in transgenic mice.
AB  - Astrocytes are known to express the gap junction forming proteins connexin30
      (Cx30) and connexin43 (Cx43), but it has remained controversial whether these
      cells also express connexin26 (Cx26). To investigate this issue further, we
      examined immunofluorescence labelling of glial connexins in wild-type vs.
      transgenic mice with targeted deletion of Cx26 in neuronal and glial cells
      (Cx26fl/fl:Nestin-Cre mice). The Cx26 antibodies utilized specifically recognized
      Cx26 and lacked cross reaction with highly homologous Cx30, as demonstrated by
      immunoblotting and immunofluorescence in Cx26-transfected and Cx30-transfected C6
      glioma cells. Punctate immunolabelling of Cx26 with these antibodies was observed
      in leptomeninges and subcortical brain regions. This labelling was absent in
      subcortical areas of Cx26fl/fl:Nestin-Cre mice, but persisted in leptomeningeal
      tissues of these mice, thereby distinguishing localization of Cx26 between
      parenchymal and non-parenchymal tissue. In subcortical brain parenchyma, Cx26
      positive puncta were often co-localized with astrocytic Cx43, and some were
      localized along astrocyte cell bodies and processes immunolabelled for glial
      fibrillary acidic protein. Cx26-positive puncta were also co-localized with
      punctate labelling of Cx47 around oligodendrocyte somata. Comparisons of Cx26
      labelling in rodent species revealed a lower density of Cx26-positive puncta and
      a more restricted distribution in subcortical regions of mouse compared with rat
      brain, perhaps partly explaining reported difficulties in detection of Cx26 in
      mouse brain parenchyma using antibodies or Cx26 gene reporters. These results
      support our earlier observations of Cx26 expression in astrocytes and its
      ultrastructural localization in individual gap junction plaques formed between
      astrocytes as well as in heterotypic gap junctions between astrocytes and
      oligodendrocytes.

PMID- 21714814
TI  - Subcortical projections to the frontal pole in the marmoset monkey.
AB  - The subcortical projections to the marmoset frontal pole were mapped with the use
      of fluorescent tracer injections. The main thalamic projections, which originated
      in both the magnocellular and parvocellular subdivisions of the mediodorsal
      nucleus, were topographically organized. Our results suggest the existence of a
      third, caudal subdivision of this nucleus, which is likely to be homologous to
      the macaque's pars densocellularis. A substantial, but not topographically
      organized, projection to Brodmann's area 10 originated in the medial part of the
      ventral anterior nucleus. Minor thalamic projections originated in the medial
      pulvinar nucleus and in the midline/intralaminar nuclei. Finally, the posterior
      thalamic group (including the limitans and suprageniculate nuclei) sent a small
      projection to rostral area 10 that has not previously been documented in
      primates. The main extrathalamic projections stemmed from the claustrum, which
      contained as many as 50% of all subcortical labelled neurons. Minor connections
      originated in the hypothalamus (mainly in the lateral anterior and lateral
      tuberal regions), dorsal periaqueductal grey matter, basal forebrain (nucleus
      basalis of Meynert and horizontal limb of the diagonal band of Broca), and
      amygdala (basal, accessory basal and lateral nuclei). The present results,
      combined with recent data on the cortical projections to area 10, reveal the
      frontal pole as a region that integrates information from multiple neural
      processing systems, including high-level sensory, limbic and working memory
      related structures. Although the pattern of subcortical projections is similar to
      that previously described in the macaque, suggesting a homologous organization,
      the present data also suggest functional distinctions between medial and lateral
      sectors of area 10.

PMID- 21714815
TI  - Estradiol-dependent catecholaminergic innervation of auditory areas in a
      seasonally breeding songbird.
AB  - A growing body of evidence suggests that gonadal steroids such as estradiol (E2)
      alter neural responses not only in brain regions associated with reproductive
      behavior but also in sensory areas. Because catecholamine systems are involved in
      sensory processing and selective attention, and because they are sensitive to E2
      in many species, they may mediate the neural effects of E2 in sensory areas.
      Here, we tested the effects of E2 on catecholaminergic innervation, synthesis and
      activity in the auditory system of white-throated sparrows, a seasonally breeding
      songbird in which E2 promotes selective auditory responses to song. Non-breeding
      females with regressed ovaries were held on a winter-like photoperiod and
      implanted with silastic capsules containing either no hormone or E2. In one
      hemisphere of the brain, we used immunohistochemistry to quantify fibers
      immunoreactive for tyrosine hydroxylase or dopamine beta-hydroxylase in the
      auditory forebrain, thalamus and midbrain. E2 treatment increased
      catecholaminergic innervation in the same areas of the auditory system in which
      E2 promotes selectivity for song. In the contralateral hemisphere we quantified
      dopamine, norepinephrine and their metabolites in tissue punches using HPLC.
      Norepinephrine increased in the auditory forebrain, but not the midbrain, after
      E2 treatment. We found that evidence of interhemispheric differences, both in
      immunoreactivity and catecholamine content that did not depend on E2 treatment.
      Overall, our results show that increases in plasma E2 typical of the breeding
      season enhanced catecholaminergic innervation and synthesis in some parts of the
      auditory system, raising the possibility that catecholamines play a role in E2
      dependent auditory plasticity in songbirds.

PMID- 21714816
TI  - Increased expression of 5-HT6 receptors in dorsolateral striatum decreases
      habitual lever pressing, but does not affect learning acquisition of simple
      operant tasks in rats.
AB  - Serotonin-6 (5-HT(6)) receptors are densely expressed in the dorsolateral
      striatum (DLS), a brain region linked to habits. Medications acting on the
      serotonergic system, including 5-HT(6) receptors, can diminish habitual and
      repetitive behaviors associated with clinical syndromes such as obsessive
      compulsive disorder, and may have implications for addiction as well. To examine
      the role of 5-HT(6) receptors in the acquisition and persistence of habitual
      behavior, we manipulated 5-HT(6) receptor expression in the DLS with herpes
      simplex virus vectors in combination with different behavioral procedures;
      control rats received a vector expressing enhanced green fluorescent protein. In
      one set of experiments, rats were tested under conditions that favor the
      acquisition of either discrete action-outcome responding or repetitive
      responding; increased 5-HT(6) receptor expression in DLS did not alter learning
      in either paradigm. In the next experiment, rats were over-trained on fixed- then
      variable-interval schedules, resulting in an escalation of lever pressing over
      sessions far in excess of that necessary to receive sucrose pellets. After
      training, rats received viral vector infusion into the DLS. Subsequently, half of
      each group underwent an omission contingency training session in which they
      received reinforcement for refraining from pressing the lever, while the other
      half served as yoked controls. A probe session under extinction conditions was
      performed the following day. Only rats that received both the 5-HT(6) vector and
      omission contingency training showed reduced lever pressing during the probe
      session. These results suggest that increasing 5-HT(6) receptor signaling in the
      DLS facilitates behavioral flexibility in the face of changing contingencies.

PMID- 21714817
TI  - p53 controls neuronal death in the CA3 region of the newborn mouse hippocampus.
AB  - It is important to determine the mechanisms controlling the number of neurons in
      the nervous system. Previously, we reported that neuronal activity plays a
      central role in controlling neuron number in the neonatal hippocampus of rodents.
      Neuronal survival requires sustained activation of the serine-threonine kinase
      Akt, which is initiated by neurotrophins and continued for several hours by
      neuronal activity and integrin signaling. Here, we focus on the CA3 region to
      show that neuronal apoptosis requires p53. As in wild-type animals, neuronal
      death occurs in the first postnatal week and ends by postnatal day (P)10 in p53(
      /-) mice. During this period, the CA3 region of p53(-/-) mice contains
      significantly lower numbers of apoptotic cells, and at the end of the death
      period, it contains more neurons than the wild type. At P10, the p53(-/-) CA3
      region contains a novel subpopulation of neurons with small soma size. These
      neurons show normal levels of tropomyosin receptor kinase receptor activation,
      but lower levels of activated Akt than the neurons with somata of normal size.
      These results suggest that p53 is the key downstream regulator of the novel
      survival-signaling pathway that regulates the number of CA3 neurons in the first
      10 days of postnatal life.

PMID- 21714818
TI  - Importance of the left auditory areas in chord discrimination in music experts as
      demonstrated by MEG.
AB  - The brain basis behind musical competence in its various forms is not yet known.
      To determine the pattern of hemispheric lateralization during sound-change
      discrimination, we recorded the magnetic counterpart of the electrical mismatch
      negativity (MMNm) responses in professional musicians, musical participants (with
      high scores in the musicality tests but without professional training in music)
      and non-musicians. While watching a silenced video, they were presented with
      short sounds with frequency and duration deviants and C major chords with C minor
      chords as deviants. MMNm to chord deviants was stronger in both musicians and
      musical participants than in non-musicians, particularly in their left
      hemisphere. No group differences were obtained in the MMNm strength in the right
      hemisphere in any of the conditions or in the left hemisphere in the case of
      frequency or duration deviants. Thus, in addition to professional training in
      music, musical aptitude (combined with lower-level musical training) is also
      reflected in brain functioning related to sound discrimination. The present
      magnetoencephalographic evidence therefore indicates that the sound
      discrimination abilities may be differentially distributed in the brain in
      musically competent and naive participants, especially in a musical context
      established by chord stimuli: the higher forms of musical competence engage both
      auditory cortices in an integrative manner.

PMID- 21714819
TI  - Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with
      idiopathic generalized epilepsy.
AB  - Epilepsy is a heterogeneous neurological disease affecting approximately 50
      million people worldwide. Genetic factors play an important role in both the
      onset and severity of the condition, with mutations in several ion-channel genes
      being implicated, including those encoding the GABA(A) receptor. Here, we
      evaluated the frequency of additional mutations in the GABA(A) receptor by direct
      sequencing of the complete open reading frame of the GABRA1 and GABRG2 genes from
      a cohort of French Canadian families with idiopathic generalized epilepsy (IGE).
      Using this approach, we have identified three novel mutations that were absent in
      over 400 control chromosomes. In GABRA1, two mutations were found, with the first
      being a 25-bp insertion that was associated with intron retention (i.e.
      K353delins18X) and the second corresponding to a single point mutation that
      replaced the aspartate 219 residue with an asparagine (i.e. D219N).
      Electrophysiological analysis revealed that K353delins18X and D219N altered
      GABA(A) receptor function by reducing the total surface expression of mature
      protein and/or by curtailing neurotransmitter effectiveness. Both defects would
      be expected to have a detrimental effect on inhibitory control of neuronal
      circuits. In contrast, the single point mutation identified in the GABRG2 gene,
      namely P83S, was indistinguishable from the wildtype subunit in terms of surface
      expression and functionality. This finding was all the more intriguing as the
      mutation exhibited a high degree of penetrance in three generations of one French
      Canadian family. Further experimentation will be required to understand how this
      mutation contributes to the occurrence of IGE in these individuals.

PMID- 21714820
TI  - Use of complementary and alternative medicine by patients with cancer in northern
      Turkey: analysis of cost and satisfaction.
AB  - AIMS AND OBJECTIVES: The aims of this study were to determine (1) the prevalence
      of complementary and alternative medicine use among patients with cancer, (2) the
      method of use of the particular therapy, (3) the reasons for using complementary
      and alternative medicine therapies, (4) the benefits experienced by the use of
      complementary and alternative medicine, (5) the source of information about
      complementary and alternative medicine therapies and, (6) the satisfaction and
      cost of complementary and alternative medicine. BACKGROUND: Complementary and
      alternative medicine consists of diverse medical and healthcare systems,
      practices and products that are not considered at present to be a part of
      conventional medicine. The majority of patients who use complementary and
      alternative medicine use more than one method. Complementary and alternative
      medicine use is more common in cases of advanced disease or poor prognosis.
      DESIGN: This is a descriptive study of complementary and alternative medicine.
      METHODS: This study was conducted in the Chemotherapy Unit at Ondokuz Mayis
      University, Faculty of Medicine, Samsun, Turkey, between 18 March 2008-30 June
      2008. Two hundred fifty-three patients with cancer, among 281 patients who
      applied to the chemotherapy clinic between these dates, agreed to take part in
      the study with whom contact could be made were included. A questionnaire
      including descriptive characteristics in collecting data, characteristics about
      diseases and their treatments, complementary and alternative medicine information
      and implementation situations and a control list about complementary and
      alternative medicine implementations were given. The collected data were
      evaluated by computer using descriptive statistics, the chi-square test and
      Student's t-test. RESULTS: In this study, 94.1% of the patients were content with
      medical treatment, 58.9% of them used complementary and alternative medicine
      treatments, 41.1% did not use any complementary and alternative medicine
      treatments. The satisfaction level of the patients with complementary and
      alternative medicine methods was slightly above mediocre (2.33 SD 0.64, on a
      scale of 1-3). The average cost per capita spent by the patients using
      complementary and alternative medicine for all the different methods was
      US$288.26. CONCLUSIONS: It was determined that although patients did not have
      enough knowledge about complementary and alternative medicine methods, the
      prevalence of complementary and alternative medicine and satisfaction levels are
      high that complementary and alternative medicine users spend substantial sums of
      money for these methods. RELEVANCE TO CLINICAL PRACTICE: To sustain medical
      treatment and prognosis of cancer, it is important for nurses to consult with
      their patients regarding the use and potential risks of some complementary and
      alternative medicine.

PMID- 21714821
TI  - Age-specific breeding success in a wild mammalian population: selection,
      constraint, restraint and senescence.
AB  - The Selection, Constraint, Restraint and Senescence Hypotheses predict how
      breeding success should vary with age. The Selection Hypothesis predicts between
      individual variation arising from quality differences; the other hypotheses
      predict within-individual variation due to differing skills or physiological
      condition (Constraint), residual reproductive lifespan (Restraint), or somatic
      and reproductive investment (Senescence). Studies tend to focus on either the
      initial increase in breeding success or later decrease; however, both require
      consideration when unravelling the underlying evolutionary processes.
      Additionally, few studies present genetic fitness measures and rarely for both
      sexes. We therefore test these four hypotheses, which are not mutually exclusive,
      in a high-density population of European badgers Meles meles. Using an 18-year
      data set (including 22 microsatellite loci), we show an initial improvement in
      breeding success with age, followed by a later and steeper rate of reproductive
      senescence in male than in female badgers. Breeding success was skewed within age
      classes, indicating the influence of factors other than age-class. This was
      partly attributable to selective appearance and disappearance of badgers
      (Selection Hypothesis). Individuals with a late age of last breeding showed a
      concave-down relationship between breeding success and experience (Constraint
      Hypothesis). There was no evidence of abrupt terminal effects; rather,
      individuals showed a concave-down relationship between breeding success and
      residual reproductive lifespan (Restraint Hypothesis), with an interaction with
      age of first breeding only in female badgers. Our results demonstrate the
      importance of investigating a comprehensive suite of factors in age-specific
      breeding success analyses, in both sexes, to fully understand evolutionary and
      population dynamics.

PMID- 21714822
TI  - The parallel evolution of dwarfism in Arctic charr is accompanied by adaptive
      divergence in mTOR-pathway gene expression.
AB  - Ecological factors have a major role in shaping natural variation in body size,
      although the underlying mechanisms are poorly understood. Icelandic Arctic charr
      (Salvelinus alpinus L.) populations represent an ideal model to understand body
      size evolution, because adult dwarfism has arisen independently on multiple
      occasions in response to parallel environmental pressures. The mechanistic target
      of rapamycin (mTOR) pathway transmits signals from the environment to control
      cellular growth and is a primary candidate to be under selection for the dwarf
      phenotype. To test this hypothesis, we modified 'inputs' to this pathway in five
      dwarf and two generalist populations (with ancestral life history and body-size
      traits), using a standardized manipulation of food intake in a common
      environment. The skeletal muscle transcript levels of 21 mTOR-pathway genes were
      quantified in 274 individuals (~6000 datapoints), and statistical modelling was
      used to elucidate sources of variation. Constitutive expression differences
      between populations were the main component of variation for around three
      quarters of the studied genes, irrespective of nutritional-state and body-size
      phenotype. There was evidence for stabilizing selection acting among populations,
      conserving the nutritionally dependent regulation of pathway genes controlling
      muscle atrophy. There were three genes (mTOR, 4E-BP-1 and IGFBP4), where the
      expression variation between dwarf and generalist populations exceeded the
      between-population variation. Divergence in the expression of these candidate
      adaptive genes was most evident during a period of rapid growth following
      sustained fasting and was directionally consistent with their functions
      regulating growth and protein synthesis. We concluded that selection has operated
      efficiently to shape gene expression evolution in Icelandic charr populations and
      that the regulation of certain mTOR-pathway genes evolved adaptively in locations
      favouring dwarfism, resulting in reduced muscle protein accretion under growth
      favouring conditions.

PMID- 21714823
TI  - Heterozygosity and survival in blue tits (Cyanistes caeruleus): contrasting
      effects of presumably functional and neutral loci.
AB  - The relationship between genetic diversity and fitness has important implications
      in evolutionary and conservation biology. This relationship has been widely
      investigated at the individual level in studies of heterozygosity-fitness
      correlations (HFC). General effects caused by inbreeding and/or local effects at
      single loci have been used as explanations of HFC, but the debate about the
      causes of HFC in open, natural populations is still ongoing. Study designs that
      control for variation in the inbreeding level of the individuals, and knowledge
      on the function and location of the markers used to measure heterozygosity, are
      fundamental to understand the causes of HFC. Here we investigated correlations
      between individual heterozygosity and estimates of survival at different life
      history stages in an open population of blue tits (Cyanistes caeruleus). For
      survival at the embryo, nestling and fledgling stage, we used a full-sibling
      approach, i.e. we controlled for the level of inbreeding. We genotyped 1496
      individuals with 79 microsatellites mapped across 25 chromosomes in the zebra
      finch (Taeniopygia guttata) that were classified either as potentially functional
      (58 loci) or as neutral (21 loci). We found different effects of standardized
      multilocus heterozygosity (SH): SH(functional)  had a negative effect on the
      probability of hatching and local recruitment of females, whereas SH(neutral) 
      had a positive effect on adult survival. The negative effects of functional loci
      are better explained by local effects, whereas the positive effects of neutral
      markers could reflect inbreeding effects in the population. Our results highlight
      the importance of considering the characteristics of the markers used in HFC
      studies and confirm the mixed effects of heterozygosity in different contexts
      (e.g. sex and life-history stage).

PMID- 21714824
TI  - Risky single-occasion drinking.

PMID- 21714825
TI  - Co-occurrence of obsessive-compulsive disorder and substance use disorder in the
      general population.
AB  - AIM: Very little is known about the relationship between obsessive-compulsive
      disorder (OCD) and substance use disorder (SUD). The aim of this study is to
      compare the co-occurrence of OCD with SUD to the co-occurrence of SUD with other
      psychiatric disorders in a representative community sample. DESIGN: In order to
      examine the association of SUD and OCD, logistic regression analyses were used
      generating odds ratios and 95% confidence intervals for life-time prevalence and
      12-month prevalence. SETTING AND PARTICIPANTS:   Cross-sectional data were
      derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS),
      a large representative sample of the Dutch population (n = 7076). MEASUREMENTS:  
      The Composite International Diagnostic Interview (CIDI) 1.1 was used to assess
      Diagnostic and Statistical Manual of Mental Disorders Axis I criteria for
      psychiatric disorders. FINDINGS:   The life-time and 12-month odds of being
      diagnosed with SUD in subjects with OCD are significantly higher than the odds of
      SUD for people without a psychiatric disorder. In men, the co-occurrence of
      substance dependence and OCD is significantly higher than the co-occurrence of
      substance dependence and other psychiatric disorders, whereas in women this co
      occurrence does not differ significantly. CONCLUSIONS:   The co-occurrence of
      substance dependence in obsessive-compulsive disorder is higher than the co
      occurrence of substance dependence in other non-obsessive-compulsive disorder DSM
      disorders, especially in men.

PMID- 21714826
TI  - Benzodiazepines revisited--will we ever learn?
AB  - AIMS: To re-examine various aspects of the benzodiazepines (BZDs), widely
      prescribed for 50 years, mainly to treat anxiety and insomnia. It is a
      descriptive review based on the Okey Lecture delivered at the Institute of
      Psychiatry, King's College London, in November 2010. METHODS: A search of the
      literature was carried out in the Medline, Embase and Cochrane Collaboration
      databases, using the codeword 'benzodiazepine(s)', alone and in conjunction with
      various terms such as 'dependence', 'abuse', etc. Further hand-searches were made
      based on the reference lists of key papers. As 60,000 references were found, this
      review is not exhaustive. It concentrates on the adverse effects, dependence and
      abuse. RESULTS: Almost from their introduction the BZDs have been controversial,
      with polarized opinions, advocates pointing out their efficacy, tolerability and
      patient acceptability, opponents deprecating their adverse effects, dependence
      and abuse liability. More recently, the advent of alternative and usually safer
      medications has opened up the debate. The review noted a series of adverse
      effects that continued to cause concern, such as cognitive and psychomotor
      impairment. In addition, dependence and abuse remain as serious problems. Despite
      warnings and guidelines, usage of these drugs remains at a high level. The
      limitations in their use both as choice of therapy and with respect to
      conservative dosage and duration of use are highlighted. The distinction between
      low-dose 'iatrogenic' dependence and high-dose abuse/misuse is emphasized.
      CONCLUSIONS: The practical problems with the benzodiazepines have persisted for
      50 years, but have been ignored by many practitioners and almost all official
      bodies. The risk-benefit ratio of the benzodiazepines remains positive in most
      patients in the short term (2-4 weeks) but is unestablished beyond that time, due
      mainly to the difficulty in preventing short-term use from extending indefinitely
      with the risk of dependence. Other research issues include the possibility of
      long-term brain changes and evaluating the role of the benzodiazepine antagonist,
      flumazenil, in aiding withdrawal.

PMID- 21714827
TI  - Widespread tau and amyloid-beta pathology many years after a single traumatic
      brain injury in humans.
AB  - While a history of a single traumatic brain injury (TBI) is associated with the
      later development of syndromes of cognitive impairment such as Alzheimer's
      disease, the long-term pathology evolving after single TBI is poorly understood.
      However, a progressive tauopathy, chronic traumatic encephalopathy, is described
      in selected cohorts with a history of repetitive concussive/mild head injury.
      Here, post-mortem brains from long-term survivors of just a single TBI (1-47
      years survival; n=39) vs. uninjured, age-matched controls (n=47) were examined
      for neurofibrillary tangles (NFTs) and amyloid-beta (Abeta) plaques using
      immunohistochemistry and thioflavine-S staining. Detailed maps of findings
      permitted classification of pathology using semiquantitative scoring systems.
      NFTs were exceptionally rare in young, uninjured controls, yet were abundant and
      widely distributed in approximately one-third of TBI cases. In addition, Abeta
      plaques were found in a greater density following TBI vs. controls. Moreover,
      thioflavine-S staining revealed that while all plaque-positive control cases
      displayed predominantly diffuse plaques, 64% of plaque-positive TBI cases
      displayed predominantly thioflavine-S-positive plaques or a mixed thioflavine-S
      positive/diffuse pattern. These data demonstrate that widespread NFT and Abeta
      plaque pathologies are present in up to a third of patients following survival of
      a year or more from a single TBI. This suggests that a single TBI induces long
      term neuropathological changes akin to those found in neurodegenerative disease.

PMID- 21714828
TI  - Acute murine H5N1 influenza A encephalitis.
AB  - Avian influenza A virus H5N1 has the proven capacity to infect humans through
      cross-species transmission, but to date, efficient human-to-human transmission is
      limited. In natural avian hosts, animal models and sporadic human outbreaks, H5N1
      infection has been associated with neurological disease. We infected BALB/c mice
      intranasally with H5N1 influenza A/Viet Nam/1203/2004 to study the immune
      response during acute encephalitis. Using immunohistochemistry and in situ
      hybridization, we compared the time course of viral infection with activation of
      immunity. By 5 days postinfection (DPI), mice had lost substantial body weight
      and required sacrifice by 7 DPI. H5N1 influenza was detected in the lung as early
      as 1 DPI, whereas infected neurons were not observed until 4 DPI. H5N1 infection
      of BALB/c mice developed into severe acute panencephalitis. Infected neurons
      lacked evidence of a perineuronal net and exhibited signs of apoptosis. Whereas
      lung influenza infection was associated with an early type I interferon (IFN)
      response followed by a reduction in viral burden concordant with appearance of
      IFN-gamma, the central nervous system environment exhibited a blunted type I IFN
      response.

PMID- 21714829
TI  - Antimicrobial resistance trends in blood culture positive Salmonella Typhi
      isolates from Pondicherry, India, 2005-2009.
AB  - Typhoid fever is caused by Salmonella enterica serovar Typhi, a major public
      health concern in developing countries. Recently, there has been an upsurge in
      the occurrence of bacterial isolates that are resistant to ciprofloxacin, and the
      emergence of broad spectrum beta-lactamases in typhoidal salmonellae constitutes
      a new challenge for the clinician. A total of 337 blood culture isolates of S.
      Typhi, isolated from Pondicherry, India, between January 2005 and December 2009,
      were investigated using phenotypic, molecular and serological methods. Of the 337
      isolates, 74 (22%) were found to be multidrug resistant (MDR) and 264 (78%)
      nalidixic acid resistant (NAR). Isolates with reduced susceptibility to
      ciprofloxacin possessed single mutations in the gyrA gene. A high rate of
      resistance (8%) was found to ciprofloxacin. All isolates with a ciprofloxacin MIC
      >= 4 mg/L possessed both double mutations in the QRDR of the gyrA gene and a
      single mutation in the parC gene. Active efflux pump mechanisms were also found
      to be involved in ciprofloxacin resistance. Finally, a large number of PFGE
      patterns (non-clonal genotypes) were observed among the S. Typhi isolates. In
      conclusion, a high rate of ciprofloxacin resistance was observed in comparison to
      other endemic areas in blood culture isolates of S. Typhi from Pondicherry,
      India, with steadily increasing NAR but decreasing MDR isolations over the study
      period. This is most likely to be due to an increased use of ciprofloxacin as a
      first-line drug of choice over more traditional antimicrobial agents for the
      treatment of typhoid fever.

PMID- 21714830
TI  - Risk factors for recurrence and death after bacteraemia: a population-based
      study.
AB  - Although most bacteraemic outcome studies have focused on mortality, a repeated
      episode(s) is another important outcome of bacteraemia. We sought to characterize
      patient factors and microbial species associated with recurrence and death from
      bacteraemia. Population-based surveillance for bacteraemia was conducted in a
      Canadian health region during 2000-2008. Episodes of bacteraemia were extracted
      and characterized. Transition intensities of both recurrence and death were
      estimated by separate multivariate Cox proportional hazards models. We identified
      9713 patients with incident episodes of bacteraemia. Within 1 year: 892 (9.2%)
      had recurrent bacteraemia, 2401 (24.7%) had died without a recurrent episode and
      330 (3.4%) had died after a recurrent episode. Independent risk factors for
      recurrence within 1 year (hazard ratio; 95% confidence interval) were: increasing
      Charlson comorbidity scores (score 1-2: 2.2; 1.8-2.7 and score 3+: 3.4; 2.8-4.2),
      origin of infection (nosocomial: 2.1; 1.8-2.6 and healthcare-associated: 2.4; 2.0
      2.8), microorganism (polymicrobial: 1.5; 1.2-2.0 and fungal: 2.8; 1.9-4.2) and
      focus of infection (verified urogenital: 0.4; 0.3-0.6). Independent risk factors
      for death within 1 year included: a recurrent bacteraemic episode 3.6 (3.1-4.0),
      increasing age and different foci of infection. This study identifies patient
      groups at risk of having a recurrent episode and dying from these infections. It
      adds recurrent bacteraemia as an independent risk factor of death within 1 year
      and may help to target patients for prevention or changes in management.

PMID- 21714831
TI  - High-resolution spatial analysis of slow wave initiation and conduction in
      porcine gastric dysrhythmia.
AB  - BACKGROUND: The significance of gastric dysrhythmias remains uncertain. Progress
      requires a better understanding of dysrhythmic behaviors, including the slow wave
      patterns that accompany or promote them. The aim of this study was to use high
      resolution spatiotemporal mapping to characterize and quantify the initiation and
      conduction of porcine gastric dysrhythmias. METHODS: High-resolution mapping was
      performed on healthy fasted weaner pigs under general anesthesia. Recordings were
      made from the gastric serosa using flexible arrays (160-192 electrodes; 7.6mm
      spacing). Dysrhythmias were observed to occur in 14 of 97 individual recordings
      (from 8 of 16 pigs), and these events were characterized, quantified and
      classified using isochronal mapping and animation. KEY RESULTS: All observed
      dysrhythmias originated in the corpus and fundus. The range of dysrhythmias
      included incomplete conduction block (n=3 pigs; 3.9+/-0.5cpm; normal range: 3.2+/
      0.2cpm) complete conduction block (n=3; 3.7+/-0.4cpm), escape rhythm (n=5; 2.0+/
      0.3cpm), competing ectopic pacemakers (n=5, 3.7+/-0.1cpm) and functional re-entry
      (n=3, 4.1+/-0.4cpm). Incomplete conduction block was observed to self-perpetuate
      due to retrograde propagation of wave fragments. Functional re-entry occurred in
      the corpus around a line of unidirectional block. 'Double potentials' were
      observed in electrograms at sites of re-entry and at wave collisions. CONCLUSIONS
      & INFERENCES: Intraoperative multi-electrode mapping of fasted weaner healthy
      pigs detected dysrhythmias in 15% of recordings (from 50% of animals), including
      patterns not previously reported. The techniques and findings described here
      offer new opportunities to understand the nature of human gastric dysrhythmias.

PMID- 21714832
TI  - Duodenal ulcer disease, gastroduodenal motor function and reflux esophagitis--a
      cross-sectional survey in a subset of Taiwanese patients.
AB  - BACKGROUND: To investigate the association between the gastric emptying rate and
      the presence of erosive esophagitis in duodenal ulcer (DU) patients among a
      population with high prevalence of Helicobacter pylori infection. METHODS: Cross
      sectional survey was performed in a cohort of 60 male patients with either active
      or healed DU, with or without the presence of erosive esophagitis. Clinical and
      social-demographic data, blood level of fasting gastrin, pepsinogen I & I/II
      ratio, and scintigraphic measurement of half emptying time (t(1/2) ) of the solid
      phase gastric emptying were evaluated. KEY RESULTS: Patients with active DU and
      erosive esophagitis tended to have higher plasma level of fasting gastrin than
      those without erosive esophagitis (75.11+/-13.74 vs 45.81+/-5.06pgmL(-1) , P =
      0.059). In the absence of H. pylori infection, patients with healed DU and
      erosive esophagitis had a trend to have longer half-emptying time (t(1/2) :
      96.5+/-6.4 vs 69.1+/-11.3min, P=0.0572) than those without erosive esophagitis,
      and statistically significant longer after excluding those diagnosed with hiatal
      hernia (t(1/2) : 100.8+/-7.9min vs 69.1+/-11.3min, P<0.05) from the former group.
      Among the healed DU patients, those with negative H. pylori infection, hiatal
      hernia and overweight (body mass index >=24) had significantly increased risk of
      severe esophagitis. CONCLUSIONS & INFERENCES: Presence of erosive esophagitis in
      a subset of Taiwanese patients with healed DU and negative H. pylori status was
      associated with slower solid phase gastric emptying.

PMID- 21714833
TI  - Patients with irritable bowel syndrome and dysmotility express antibodies against
      gonadotropin-releasing hormone in serum.
AB  - BACKGROUND: The etiology of irritable bowel syndrome (IBS) and dysmotility is in
      most cases unknown. Organic, pathognomonic changes have not been described. We
      have previously demonstrated sporadic expressions of antibodies against
      gonadotropin-releasing hormone (GnRH) in serum from these patients. The aim of
      this study was to screen for the presence of GnRH antibodies in healthy subjects
      and patients with gastrointestinal (GI) diseases. METHODS: Consecutive patients
      suffering from either IBS, idiopathic dysmotility, GI complaints secondary to
      diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were
      included. Healthy blood donors served as controls. Blood samples were taken for
      analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical
      records were scrutinized with respect to duration of symptoms, co-existing
      diseases, drug treatments, hereditary factors, and laboratory analyses. KEY
      RESULTS: Healthy controls expressed low levels of GnRH IgM antibodies in a
      prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility
      patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients
      with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as
      controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or
      IBD had the same or lower levels of antibodies. There were no associations
      between antibodies, other co-existing diseases or laboratory analyses.
      CONCLUSIONS & INFERENCES: Higher levels of GnRH IgM antibodies were detected in
      patients with IBS and dysmotility, but not organic GI diseases, compared with
      healthy controls. These findings suggest that IBS and dysmotility to some extent
      may be of an autoimmune origin.

PMID- 21714834
TI  - Biological control of anthracnose (Colletotrichum gloeosporioides) in yam by
      Streptomyces sp.MJM5763.
AB  - AIM: To find a suitable biocontrol agent for yam anthracnose caused by
      Colletotrichum gloeosporioides. METHODS AND RESULTS: An actinobacterial strain,
      MJM5763, showing strong antifungal activity, multiple biocontrol and plant growth
      promoting traits was isolated from a yam cultivation field in Yeoju, South Korea.
      Based on morphological and physiological characteristics and analysis of the 16S
      rDNA sequence, strain MJM5763 was identified as a novel strain of Streptomyces
      and was designated as Streptomyces sp. MJM5763. Treatment with MJM5763 and the
      crude culture filtrate extract (CCFE) was effective in suppressing anthracnose in
      detached yam leaves in vitro and reduced incidence and severity of anthracnose in
      yam plants under greenhouse conditions. The CCFE treatment was the most effective
      of all the treatments and reduced the anthracnose severity by 85-88% and the
      incidence by 79-81%, 90 days after inoculation with the pathogen. CCFE treatment
      was also effective under field conditions and showed a reduction of 86 and 75% of
      anthracnose severity and incidence, respectively. CONCLUSION: Streptomyces sp.
      strain MJM5763 was effective in biocontrolling anthracnose in yam caused by C.
      gloeosporioides. SIGNIFICANCE AND IMPACT OF THE STUDY: Streptomyces sp. MJM5763
      is a potential alternative to chemical fungicides for reducing yield losses to
      anthracnose in yam.

PMID- 21714835
TI  - Fusarium species complex and mycotoxins in grain maize from maize hybrid trials
      and from grower's fields.
AB  - AIMS: To quantify and to compare the occurrence of Fusarium species in maize
      kernels and stalk pieces, to analyse mycotoxins in kernels and maize crop
      residues, to evaluate two approaches to obtain kernel samples and to compare two
      methods for mycotoxin analyses. METHODS AND RESULTS: The occurrence of Fusarium
      species in maize kernels and stalk pieces from a three-year maize hybrid trial
      and 12 kernel samples from grower's fields was assessed. Nine to 16 different
      Fusarium species were detected in maize kernels and stalks. In kernels, F.
      graminearum, F. verticillioides and F. proliferatum were the most prevalent
      species whereas in stalks, they were F. equiseti, F. proliferatum and F.
      verticillioides. In 2006, 68% of the kernel samples exceeded the recommended
      limit for pig feed for deoxynivalenol (DON) and 42% for zearalenone (ZON),
      respectively. Similarly, 75% of the samples from grower's fields exceeded the
      limits for DON and 50% for ZON. In maize crop residues, toxin concentrations
      ranged from 2.6 to 15.3 mg kg(-1) for DON and from 0.7 to 7.4 mg kg(-1) for ZON.
      Both approaches to obtain maize kernel samples were valid, and a strong
      correlation between mycotoxin analysis using ELISA and LC-MS/MS was found.
      CONCLUSIONS: The contamination of maize kernels, stalk pieces and remaining crop
      residues with various mycotoxins could pose a risk not only to animal health but
      also to the environment. With the hand-picked sample, the entire Fusarium complex
      can be estimated, whereas combine harvested samples are more representative for
      the mycotoxin contents in harvested goods. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first multi-year study investigating mycotoxin contamination in maize
      kernels as well as in crop residues. The results indicate a high need to identify
      cropping factors influencing the infection of maize by Fusarium species to
      establish recommendations for growers.

PMID- 21714836
TI  - Selection of antagonistic bacteria isolated from the Physalis peruviana
      rhizosphere against Fusarium oxysporum.
AB  - AIMS: Cape gooseberries (Physalis peruviana) have become increasingly important
      in Colombia for both domestic consumption and the international export market.
      Vascular wilting caused by Fusarium oxysporum is the most damaging disease to P.
      peruviana crops in Colombia. The control of this pathogen is mainly carried out
      by chemical and cultural practices, increasing production costs and generating
      resistance. Therefore, the objectives of this study were to test rhizobacteria
      isolates from P. peruviana rhizosphere against F. oxysporum under in vitro and in
      vivo conditions. METHODS AND RESULTS: Over 120 strains were isolated, and five
      were selected for their high inhibition of F. oxysporum growth and conidia
      production under in vitro conditions. These strains inhibited growth by 41-58%
      and reduced three- to fivefold conidia production. In the in vivo assays, all the
      tested isolates significantly reduced fungal pathogenicity in terms of virulence.
      Isolate B-3.4 was the most efficient in delaying the onset of the first symptoms.
      All isolates were identified as belonging to the genus Pseudomonas except for A
      19 (Bacillus sp.). CONCLUSIONS: Our results confirmed that there are prospective
      rhizobacteria strains that can be used as biological control agents; some of them
      being able to inhibit in vitro F. oxysporum growth and sporulation. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Incorporating these bacteria into biological control
      strategies for the disease that causes high economical losses in the second most
      exported fruit from Colombia would result in a reduced impact on environment and
      economy.

PMID- 21714837
TI  - Isolation of a thermotolerant bacterium producing medium-chain-length
      polyhydroxyalkanoate.
AB  - AIMS: The aim of this study was to isolate a thermotolerant micro-organism that
      produces polyhydroxyalkanoates (PHAs) composed of medium-chain-length (mcl) HA
      units from a biodiesel fuel (BDF) by-product as a carbon source. METHODS AND
      RESULTS: We successfully isolated a thermotolerant micro-organism, strain SG4502,
      capable to accumulate mcl-PHA from a BDF by-product as a carbon source at a
      cultivation temperature of 45 degrees C. The strain could also produce mcl-PHA
      from acetate, octanoate and dodecanoate as sole carbon sources at cultivation
      temperatures up to 55 degrees C. Taxonomic studies and 16S rRNA gene sequence
      analysis revealed that strain SG4502 was phylogenetically affiliated with species
      of the genus Pseudomonas. This study is the first report of PHA synthesis by a
      thermotolerant Pseudomonas. CONCLUSIONS: A novel thermotolerant bacterium capable
      to accumulate mcl-PHA from a BDF by-product was successfully isolated.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A major issue regarding industrial
      production of microbial PHAs is their much higher production cost compared with
      conventional petrochemical-based plastic materials. Especially significant are
      the cost of a fermentative substrate and the running cost to maintain a
      temperature suitable for microbial growth. Thus, strain SG4502, isolated in this
      study, which assimilates BDF by-product and produces PHA at high temperature,
      would be very useful for practical application in industry.

PMID- 21714838
TI  - Survival of Salmonella on cuts of beef carcasses subjected to dry aging.
AB  - AIMS: The aim of this study was to determine the survival of 15 different strains
      of Salmonella of selected serotypes during prolonged cold storage of beef.
      METHODS AND RESULTS: Fifteen strains of eight different serotypes of Salmonella
      were spiked onto fresh cuts beef portions, and the survival was followed during
      storage in a laboratory cooling system. Over a 14-day period, all strains were
      reduced significantly in numbers; however, strains of Salmonella Typhimurium
      DT104 and Salmonella Enteritidis PT4 and PT8 survived significantly longer than
      strains of the serovars Dublin, Derby, Infantis and Newport. For five selected
      strains, the observations were verified in a pilot plant cooling facility
      mimicking industrial cooling. No significant differences in reduction were found
      between the two cooling methods. CONCLUSIONS: A significant reduction in
      Salmonella can be obtained by dry aging of beef during cold storage but the
      survival is strain dependent. SIGNIFICANCE AND IMPACT OF THE STUDY: From a
      hygienic point of view, cold storage of unpacked beef, which is still performed
      in small slaughterhouses, is a good alternative to vacuum packaging.

PMID- 21714839
TI  - Effects of Mn levels on resistance of Bacillus megaterium spores to heat,
      radiation and hydrogen peroxide.
AB  - AIMS: To determine the effects of Mn levels in Bacillus megaterium sporulation
      and spores on spore resistance. METHODS AND RESULTS: Bacillus megaterium was
      sporulated with no added MnCl(2) and up to 1 mmol l(-1) MnCl(2). The resultant
      spores were purified and loosely bound Mn removed, and spore Mn levels were found
      to vary c. 100-fold. The Mn level had no effect on spore gamma-radiation
      resistance, but B. megaterium spores with elevated Mn levels had higher
      resistance to UVC radiation (as did Bacillus subtilis spores), wet and dry heat
      and H(2)O(2). However, levels of dipicolinic acid and the DNA-protective
      alpha/beta-type small, acid-soluble spore proteins were the same in spores with
      high and low Mn levels. CONCLUSIONS: Mn levels either in sporulation or in spores
      are important factors in determining levels of B. megaterium spore resistance to
      many agents, with the exception of gamma-radiation. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The Mn level in sporulation is an important factor to consider when
      resistance properties of B. megaterium spores are examined, and will influence
      the UV resistance of B. subtilis spores, some of which are used as biological
      dosimeters.

PMID- 21714840
TI  - Depth by ultrasound from skin surface to the C6 transverse process while applying
      pressure.
AB  - BACKGROUND: A stellate ganglion block is commonly performed on the anterior
      tubercle of sixth cervical spine's transverse process. When the procedure is
      performed, identifying the anatomical landmarks and confirming the depth of the
      needle insertion to the transverse process are essential for ensuring safety. The
      purpose of this study was to determine the depth of the needle insertion from the
      skin to the transverse process for a safe stellate ganglion block. METHODS: One
      hundred patients were enrolled for this study. The patients' heights, weights,
      and neck circumferences were measured. In the supine position, the anterior
      tubercle of the transverse process were palpated and pressed with the examiner's
      fingers. While spreading the fingers, an ultrasound probe was placed with the
      same strength as the fingers and the depth from the skin to the transverse
      process was measured. RESULTS: The mean depth from the skin to the transverse
      process in men was 9.5 +/- 2.7 mm on the left side and 9.7 +/- 2.5 mm on the
      right side, whereas in women, it was 8.0 +/- 2.2 mm on the left side and 8.2 +/-
      2.0 mm on the right side. There was no significant difference between the right
      and left sides among or between the genders but men showed greater depths than
      women. Although both genders showed a correlation between body mass index and
      depth, only men showed a correlation between the neck circumference and depth.
      CONCLUSIONS: In this study, the mean depth from the skin to the transverse
      process did not exceed 10 mm in both genders and the maximum depth was 16.6 mm.

PMID- 21714841
TI  - Progesterone prevents nerve injury-induced allodynia and spinal NMDA receptor
      upregulation in rats.
AB  - BACKGROUND: Peripheral nerve injury-evoked neuropathic pain still remains a
      therapeutic challenge. Recent studies support the notion that progesterone, a
      neuroactive steroid, may offer a promising perspective in pain modulation.
      OBJECTIVES: Evaluate the effect of progesterone administration on the development
      of neuropathic pain-associated allodynia and on the spinal expression of N-Methyl
      D-Aspartate Receptor subunit 1 (NR1), its phosphorylated form (pNR1), and the
      gamma isoform of protein kinase C (PKCgamma), all key players in the process of
      central sensitization, in animals subjected to a sciatic nerve constriction.
      METHODS: Male Sprague-Dawley rats were subjected to a sciatic nerve single
      ligature constriction and treated with daily subcutaneous injections of
      progesterone (16 mg/kg) or vehicle. The development of hindpaw mechanical and
      thermal allodynia was assessed using the von Frey and Choi tests, respectively.
      Twenty two days after injury, the number of neuronal profiles exhibiting NR1,
      pNR1, or PKCgamma immunoreactivity was determined in the dorsal horn of the
      lumbar spinal cord. RESULTS: Injured animals receiving progesterone did not
      develop mechanical allodynia and showed a significantly lower number of painful
      responses to cold stimulation. In correlation with the observed attenuation of
      pain behaviors, progesterone administration significantly reduced the number of
      NR1, pNR1, and PKCgamma immunoreactive neuronal profiles. CONCLUSIONS: Our
      results show that progesterone prevents allodynia in a rat model of sciatic nerve
      constriction and reinforce its role as a potential treatment for neuropathic
      pain.

PMID- 21714842
TI  - MCP-1 and IL-8 as pain biomarkers in fibromyalgia: a pilot study.
AB  - OBJECTIVE: Although fibromyalgia (FM) is traditionally a non-inflammatory
      condition, emerging data also suggest that FM has an immunologic component.
      Previous studies have reported that peripheral blood concentrations of two
      chemokines (i.e., interleukin-8 [IL-8] and monocyte chemotactic protein-1 [MCP
      1]) were elevated in FM patients compared with normal controls. We sought to
      determine the longitudinal relationships of changes in the levels (picogram/mL)
      of IL-8 and MCP-1 with changes in the severity of FM-related pain. DESIGN:
      Secondary data analysis of a cohort of 16 FM subjects who provided blood samples
      at two time points: week 1 and week 12. Setting.  Urban rheumatology clinic
      practices. PATIENTS: Individuals who met the American College of Rheumatology
      1990 criteria for FM. OUTCOME MEASURES: Changes from week 1 to week 12 of the
      following variables: Brief Pain Inventory (BPI) pain severity and plasma
      concentrations of IL-8 and MCP-1. RESULTS:   Change in BPI pain severity was
      significantly associated with changes in IL-8 and MCP-1 plasma concentrations.
      Specifically, for each unit increase in the change of BPI pain severity, IL-8
      increased by 2.5 pg/mL (P = 0.03) and MCP-1 increased by 9.4 pg/mL (P = 0.006).
      None of the covariates (i.e., body mass index, medications, severity of
      depression, and overall FM burden) were significantly associated with either
      chemokines. CONCLUSION:   Although preliminary, our findings raise the hypothesis
      that IL-8 and MCP-1 may be involved in the pathogenesis of FM. If replicated in a
      larger study, IL-8 and MCP-1 may assist in determining prognosis and in
      monitoring of treatment response.

PMID- 21714843
TI  - Unintended epidural placement of a thoracic paravertebral catheter in a patient
      with severe chest trauma.
AB  - OBJECTIVE: Severe pain can lead to ventilatory compromise in patients with
      multiple rib fractures. Regional anesthetic techniques, including continuous
      thoracic paravertebral and thoracic epidural blocks, can be useful in reducing
      this pain and subsequent morbidity due to respiratory compromise. Thoracic
      paravertebral block can result in significant complications. Presumed epidural
      spread of injected medication has been described with thoracic paravertebral
      block. High-quality radiographic images of an attempted placement of a thoracic
      paravertebral catheter in the epidural space have not been reported. We present
      these images to highlight the occurrence of this complication. SETTINGS AND
      PATIENTS: In this case, we report an attempted placement of a thoracic
      paravertebral catheter that passed into the epidural space. High-fidelity, three
      dimensional computer tomography images and the management of the unintended
      epidural catheterization are presented. RESULTS AND CONCLUSIONS: In the setting
      of severe chest trauma, the potential risk of unintended placement of an intended
      thoracic paravertebral catheter in the epidural space is graphically illustrated
      as a potential risk of this procedure.

PMID- 21714844
TI  - Testing an educational nursing intervention for pain assessment and management in
      older people.
AB  - OBJECTIVE: This study aimed to examine the effectiveness of a structured
      educational nursing intervention on pain assessment and management in older
      hospitalized people. DESIGN: A non-equivalent control group interventional
      design. SETTING: Geriatric evaluation and management units in two metropolitan
      Australian hospitals. PATIENTS: In total, 192 patients participated, with 32
      different patients recruited consecutively for the pre-intervention,
      intervention, and 3-month post-intervention stages from each unit. INTERVENTIONS:
      Nurses in the intervention group received a structured intervention comprising 6
      hours of instruction and 2 hours of clinical demonstration. Nurses in the control
      group received "usual" staff development activities. OUTCOME MEASURES: Five
      assessment tools for pain were used: the visual analog scale, the Faces Pain
      Scale-Revised, the Short-Form McGill Pain Questionnaire, the Pain Assessment in
      Advanced Dementia Tool, and the Abbey Pain Scale. Data were also collected on
      nurses' use of pain assessment tools and their use of non-pharmacological and
      pharmacological methods of managing pain. RESULTS: Improvements were observed in
      pain intensity at rest and on movement in the intervention unit at the post
      intervention stage and at the 3-month post-intervention stage. There was also a
      trend for patients to be prescribed analgesics on a fixed dose schedule following
      implementation of the program in the intervention unit. CONCLUSIONS: The
      comprehensive intervention enabled change in practice and improvements in pain
      intensity, and the assessment and management of pain. Future research is needed
      on implementing the intervention with a multidisciplinary team of health
      professionals in a subacute environment.

PMID- 21714845
TI  - The impact of conversion from prograf to generic tacrolimus in liver and kidney
      transplant recipients with stable graft function.
AB  - Bioequivalence of the recently available generic tacrolimus formulation,
      manufactured by Sandoz, to the reference product (Prograf; Astellas Pharma,
      Tokyo, Japan) has been demonstrated in healthy subjects. However, the safety and
      efficacy of substitution with generic tacrolimus in transplant patients have not
      been evaluated. Tacrolimus trough concentrations and indices of liver and kidney
      function were recorded before and after generic substitution in 48 liver and 55
      kidney transplant recipients. In liver transplant patients, the mean tacrolimus
      concentration/dose (C/D) ratio (+/- SD) was 184.1 (+/- 123.2)
      ([ng/mL]/[mg/kg/day]) for the reference product and 154.7 (+/- 87.8)
      ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). The mean C/D-ratios in
      kidney transplant patients were 125.3 (+/- 92.7) and 110.4 (+/- 79.2)
      ([ng/mL]/[mg/kg/day]) for the reference and generic products, respectively (p <
      0.05). Actual trough concentrations declined by an average of 1.98 ng/mL in liver
      and 0.87 ng/mL in kidney transplant patients following the switch, after
      accounting for all significant covariates. No change was observed in biochemical
      indices of liver or kidney function and no cases of acute rejection occurred
      following the substitution. These results suggest that transplant patients
      currently taking the reference tacrolimus formulation may be safely switched to
      the Sandoz-generic product provided trough concentrations are closely monitored
      following the substitution.

PMID- 21714846
TI  - Do NK cells contribute to the pathophysiology of transplant-associated thrombotic
      microangiopathy?
AB  - Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening
      complication caused by the aggregation of platelets exposed to the thrombogenic
      subendothelial matrix of injured endothelial cells. Here, we present a case of a
      patient transplanted for idiopathic aplastic anemia with a T-cell depleted
      hematopoietic stem cell graft from an HLA-C mismatched unrelated donor. At day 7
      posttransplant, she suffered from acute renal failure with hematuria. The
      presence of numerous schistocytes, an increased level of lactate dehydrogenase
      and a renal biopsy with multiple vascular injuries confirmed the diagnosis of
      severe TA-TMA. At day 14, she developed graft versus host disease and died 7
      months posttransplantation of multiorgan failure. At day 15, we observed a
      sizable population of natural killer (NK) cells in the peripheral blood, the
      number of which reached 0.8 G/L at 4 months posttransplant. Most NK cells lacked
      inhibitory killer immunoglobulin-like receptors (KIR) specific for the KIR
      ligands expressed in the patient. NK cells were also abundantly present in
      pericardial and pleural fluids and had invaded the kidney, where they colocalized
      with the renal vasculopathy. Because there are several mechanisms through which
      NK cells and platelets can activate each other reciprocally, it is conceivable
      that NK cells contribute to TA-TMA and its progression.

PMID- 21714847
TI  - KIR-HLA mismatching in human renal allograft transplantation: emergence of a new
      concept.

PMID- 21714848
TI  - Renal transplantation in patients with AA amyloidosis nephropathy: results from a
      French multicenter study.
AB  - Although end-stage renal disease related to AA amyloidosis nephropathy is well
      characterized, there are limited data concerning patient and graft outcome after
      renal transplantation. We performed a multicentric retrospective survey to assess
      the graft and patient survival in 59 renal recipients with AA amyloidosis. The
      recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall,
      5- and 10-year patient survival was significantly lower for the AA amyloidosis
      patients than for a control group of 177 renal transplant recipients (p = 0.0001,
      0.028 and 0.013, respectively). In contrast, we did not observe any statistical
      differences in the 5- and 10- year graft survival censored for death between two
      groups. AA amyloidosis-transplanted patients exhibited a high proportion of
      infectious complications after transplantation (73.2%). Causes of death included
      both acute cardiovascular events and fatal septic complications. Multivariate
      analysis demonstrated that the recurrence of AA amyloidosis on the graft
      (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1-year
      increase = 1.06, p = 0.03) were significantly associated with risk of death.
      Finally, patients with AA amyloidosis nephropathy are eligible for renal
      transplantation but require careful management of both cardiovascular and
      infectious complications to reduce the high risk of mortality.

PMID- 21714849
TI  - KIR-ligand mismatches are associated with reduced long-term graft survival in HLA
      compatible kidney transplantation.
AB  - Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system
      with the ability to detect HLA class I disparities via killer-cell immunoglobulin
      like receptors (KIR). To test whether such KIR-ligand mismatches contribute to
      the rejection of human solid allografts, we did a retrospective cohort study of
      397 HLA-DR-compatible kidney transplantations and determined the KIR and HLA
      genotypes of recipients and the HLA genotypes of donors. In transplantations
      compatible for HLA-A, HLA-B and HLA-DR (n = 137), in which a role for T cells and
      HLA antibodies in rejection was minimized, KIR-ligand mismatches were associated
      with an approximately 25% reduction in 10-year death-censored graft survival (p =
      0.043). This effect was comparable to the effect of classical HLA-A and HLA-B
      incompatibility, and in HLA-A,-B-incompatible transplantations (n = 260) no
      significant additional effect of KIR-ligand mismatches was observed. Multivariate
      Cox regression analysis confirmed the effect of KIR-ligand mismatching as an
      independent risk factor in HLA-A,-B,-DR-compatible transplantations (hazard ratio
      2.29, range 1.03-5.10, p = 0.043). This finding constitutes the first indication
      that alloreactive NK cells may thwart the success of HLA-compatible kidney
      transplantations, and suggests that suppression of NK-cell activity can improve
      the survival of such kidney grafts.

PMID- 21714850
TI  - Late night activity regarding stroke codes: LuNAR strokes.
AB  - BACKGROUND: There is diurnal variation for cardiac arrest and sudden cardiac
      death. Stroke may show a similar pattern. We assessed whether strokes presenting
      during a particular time of day or night are more likely of vascular etiology.
      AIM: To compare emergency department stroke codes arriving between 22:00 and 8:00
      hours (LuNAR strokes) vs. others (n-LuNAR strokes). The purpose was to determine
      if late night strokes are more likely to be true strokes or warrant acute tissue
      plasminogen activator evaluations. METHODS: We reviewed prospectively collected
      cases in the University of California, San Diego Stroke Team database gathered
      over a four-year period. Stroke codes at six emergency departments were
      classified based on arrival time. Those arriving between 22:00 and 8:00 hours
      were classified as LuNAR stroke codes, the remainder were classified as 'n
      LuNAR'. Patients were further classified as intracerebral hemorrhage, acute
      ischemic stroke not receiving tissue plasminogen activator, acute ischemic stroke
      receiving tissue plasminogen activator, transient ischemic attack, and nonstroke.
      Categorical outcomes were compared using Fisher's Exact test. Continuous outcomes
      were compared using Wilcoxon's Rank-sum test. RESULTS: A total of 1607 patients
      were included in our study, of which, 299 (19%) were LuNAR code strokes. The
      overall median NIHSS was five, higher in the LuNAR group (n-LuNAR 5, LuNAR 7;
      P=0.022). There was no overall differences in patient diagnoses between LuNAR and
      n-LuNAR strokes (P=0.169) or diagnosis of acute ischemic stroke receiving tissue
      plasminogen activator (n-LuNAR 191 (14.6%), LuNAR 42 (14.0%); P=0.86). Mean
      arrival to computed tomography scan time was longer during LuNAR hours (n-LuNAR
      54.9+/-76.3 min, LuNAR 62.5+/-87.7 min; P=0.027). There was no significant
      difference in 90-day mortality (n-LuNAR 15.0%, LuNAR 13.2%; P=0.45). CONCLUSIONS:
      Our stroke center experience showed no difference in diagnosis of acute ischemic
      stroke between day and night stroke codes. This similarity was further supported
      in similar rates of tissue plasminogen activator administration. Late night
      strokes may warrant a more rapid stroke specialist evaluation due to the longer
      time elapsed from symptom onset and the longer time to computed tomography scan.

PMID- 21714851
TI  - Older adults' perceptions of weakness and ageing.
AB  - BACKGROUND: Age-related weakness, or sarcopenia, has been related to functional
      disability, falls, frailty and mortality. Although it is one of the most common
      symptoms older adults link to their functional abilities, to date, no studies
      have explored older adults' perceptions of weakness and its association with
      ageing. AIMS AND OBJECTIVES: To understand the meaning of weakness for older
      adults' and their perceptions of its association with ageing. DESIGNS: A
      qualitative descriptive design involved in-depth interviews with 13 community
      dwelling older adults. RESULTS: Weakness was described primarily in two ways: (i)
      inability and (ii) inward turning. The extreme of weakness, as giving up and
      giving in, which older adults applied to others, not themselves, prompted them to
      engage in several efforts at staying strong. These included motivating self-talk,
      achieving balance, keeping busy and active, and self-validating as a strong
      person. Older adults' perceptions of the association between weakness and ageing
      were variable and characterized by considerable ambiguity. IMPLICATIONS FOR
      PRACTICE: Nurses must be alert to both the visible and subtler dimensions of
      weakness. It is important to engage older adults in active strategies that
      enhance muscle strength while capitalizing on their self-motivating and
      validating efforts at staying strong.

PMID- 21714852
TI  - Nurses' experience of loss on the death of older persons in long-term residential
      care: findings from an interpretative phenomenological study.
AB  - BACKGROUND: Little is known of the experience of loss among nurses working with
      older persons in long-stay settings. OBJECTIVES: The aim of this study was to
      explore and describe the experience of loss among nurses working in a long-term
      residential care setting. DESIGN: Interpretative Phenomenological Analysis (IPA)
      was the method adopted. Data was collected by semi-structured interviews
      undertaken with seven nurses. RESULTS: The findings revealed three main themes:
      'life's final journey', 'family' and 'professional carer'. CONCLUSIONS: The
      experience of loss on the death of an older person is described by nurses in the
      context of the care they give at end of life, and the relationships nurses
      developed with the older person's family. Where the older person has no contact
      with family, nurses become the 'family' and this contributed to the feeling of
      loss experienced. Finally, the loss experienced by nurses when an older person
      dies suddenly can often be emotive. RELEVANCE TO CLINICAL PRACTICE: Supporting
      nurses in their provision of end-of-life care to older persons is essential.
      Nurses' attempts to keep memories of deceased residents alive by remembrance,
      helps place loss in the context of acknowledgment of the person's life.

PMID- 21714853
TI  - Oxymatrine induces human pancreatic cancer PANC-1 cells apoptosis via regulating
      expression of Bcl-2 and IAP families, and releasing of cytochrome c.
AB  - BACKGROUND: Oxymatrine, an isolated extract from traditional Chinese herb Sophora
      Flavescens Ait, has been traditionally used for therapy of anti-hepatitis B
      virus, anti-inflammation and anti-anaphylaxis. The present study was to
      investigate the anti-cancer effect of oxymatrine on human pancreatic cancer PANC
      1 cells, and its possible molecular mechanism. METHODS: The effect of oxymatrine
      on the viability and apoptosis was examined by methyl thiazolyl tetrazolium and
      flow cytometry analysis. The expression of Bax, Bcl-2, Bcl-x (L/S), Bid, Bad,
      HIAP-1, HIAP-2, XIAP, NAIP, Livin and Survivin genes was accessed by RT-PCR. The
      levels of cytochrome c and caspase 3 protein were assessed by Western blotting.
      RESULTS: Oxymatrine inhibited cell viability and induced apoptosis of PANC-1
      cells in a time- and dose-dependent manner. This was accompanied by down
      regulated expression of Livin and Survivin genes while the Bax/Bcl-2 ratio was
      upregulated. Furthermore, oxymatrine treatment led to the release of cytochrome c
      and activation of caspase-3 proteins. CONCLUSION: Oxymatrine can induce apoptotic
      cell death of human pancreatic cancer, which might be attributed to the
      regulation of Bcl-2 and IAP families, release of mitochondrial cytochrome c and
      activation of caspase-3.

PMID- 21714854
TI  - Controlling behavior, power relations within intimate relationships and intimate
      partner physical and sexual violence against women in Nigeria.
AB  - BACKGROUND: Controlling behavior is more common and can be equally or more
      threatening than physical or sexual violence. This study sought to determine the
      role of husband/partner controlling behavior and power relations within intimate
      relationships in the lifetime risk of physical and sexual violence in Nigeria.
      METHODS: This study used secondary data from a cross-sectional nationally
      representative survey collected by face-to-face interviews from women aged 15 -
      49 years in the 2008 Nigeria Demographic and Health Survey. Utilizing a
      stratified two-stage cluster sample design, data was collected frrm 19 216
      eligible with the DHS domestic violence module, which is based on the Conflict
      Tactics Scale (CTS). Multivariate logistic regression analysis was used to
      determine the role of husband/partner controlling behavior in the risk of ever
      experiencing physical and sexual violence among 2877 women aged 15 - 49 years who
      were currently or formerly married or cohabiting with a male partner. RESULTS:
      Women who reported controlling behavior by husband/partner had a higher
      likelihood of experiencing physical violence (RR = 3.04; 95% CI: 2.50 - 3.69),
      and women resident in rural areas and working in low status occupations had
      increased likelihood of experiencing physical IPV. Controlling behavior by
      husband/partner was associated with higher likelihood of experiencing physical
      violence (RR = 4.01; 95% CI: 2.54 - 6.34). In addition, women who justified wife
      beating and earned more than their husband/partner were at higher likelihood of
      experiencing physical and sexual violence. In contrast, women who had decision
      making autonomy had lower likelihood of experiencing physical and sexual
      violence. CONCLUSION: Controlling behavior by husband/partner significantly
      increases the likelihood of physical and sexual IPV, thus acting as a precursor
      to violence. Findings emphasize the need to adopt a proactive integrated approach
      to controlling behavior and intimate partner violence within the society.

PMID- 21714855
TI  - Dealing with the difficult student in emergency medicine.
AB  - Dealing with a student who is perceived as difficult to work with or teach is
      inevitable in any academic physician's career. This paper will outline the basic
      categories of these difficulties pertinent to Emergency Medicine rotations in
      order to facilitate appropriate identification of problems. Strategies for
      evaluation and reporting of the difficult student are presented. Remediation,
      based on the type of difficulty, is addressed. Timeliness of reporting,
      evaluation, and feedback are invaluable to allow for appropriate assessment of
      the outcome of the remediation plan.

PMID- 21714856
TI  - Disease activity and low physical activity associate with number of hospital
      admissions and length of hospitalisation in patients with rheumatoid arthritis.
AB  - INTRODUCTION: Substantial effort has been devoted for devising effective and safe
      interventions to reduce preventable hospital admissions in chronic disease
      patients. In rheumatoid arthritis (RA), identifying risk factors for admission
      has important health policy implications, but knowledge of which factors cause or
      prevent hospital admissions is currently lacking. We hypothesised that disease
      activity/severity and physical activity are major predictors for the need of
      hospitalisation in patients with RA. METHODS: A total of 244 RA patients were
      assessed for: physical activity (International Physical Activity Questionnaire),
      RA activity (C-reactive protein: CRP; disease activity score: DAS28) and
      disability (Health Assessment Questionnaire: HAQ). The number of hospital
      admissions and length of hospitalisation within a year from baseline assessment
      were collected prospectively. RESULTS: Disease activity and disability as well as
      levels of overall and vigorous physical activity levels correlated significantly
      with both the number of admissions and length of hospitalisation (P < 0.05);
      regression analyses revealed that only disease activity (DAS28) and physical
      activity were significant independent predictors of numbers of hospital
      admissions (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) =
      0.999, P = 0.046)) and length of hospitalisation (DAS28: (exp(B) = 1.795, P =
      0.002 and physical activity: (exp(B) = 0.999, P = 0.046). Sub-analysis of the
      data demonstrated that only 19% (n = 49) of patients engaged in recommended
      levels of physical activity. CONCLUSIONS: This study provides evidence that
      physical activity along with disease activity are important predictors of the
      number of hospital admissions and length of hospitalisation in RA. The
      combination of lifestyle changes, particularly increased physical activity along
      with effective pharmacological therapy may improve multiple health outcomes as
      well as cost of care for RA patients.

PMID- 21714857
TI  - High-dose fenoldopam reduces postoperative neutrophil gelatinase-associated
      lipocaline and cystatin C levels in pediatric cardiac surgery.
AB  - INTRODUCTION: The aim of the study was to evaluate the effects of high-dose
      fenoldopam, a selective dopamine-1 receptor, on renal function and organ
      perfusion during cardiopulmonary bypass (CPB) in infants with congenital heart
      disease (CHD). METHODS: A prospective single-center randomized double-blind
      controlled trial was conducted in a pediatric cardiac surgery department. We
      randomized infants younger than 1 year with CHD and biventricular anatomy (with
      exclusion of isolated ventricular and atrial septal defect) to receive blindly a
      continuous infusion of fenoldopam at 1 MUg/kg/min or placebo during CPB.
      Perioperative urinary and plasma levels of neutrophil gelatinase-associated
      lipocaline (NGAL), cystatin C (CysC), and creatinine were measured to assess
      renal injury after CPB. RESULTS: We enrolled 80 patients: 40 received fenoldopam
      (group F) during CPB, and 40 received placebo (group P). A significant increase
      of urinary NGAL and CysC levels from baseline to intensive care unit (ICU)
      admission followed by restoration of normal values after 12 hours was observed in
      both groups. However, urinary NGAL and CysC values were significantly reduced at
      the end of surgery and 12 hours after ICU admission (uNGAL only) in group F
      compared with group P (P = 0.025 and 0.039, respectively). Plasma NGAL and CysC
      tended to increase from baseline to ICU admission in both groups, but they were
      not significantly different between the two groups. No differences were observed
      on urinary and plasma creatinine levels and on urine output between the two
      groups. Acute kidney injury (AKI) incidence in the postoperative period, as
      indicated by pRIFLE classification (pediatric score indicating Risk, Injury,
      Failure, Loss of function, and End-stage kidney disease level of renal damage)
      was 50% in group F and 72% in group P (P = 0.08; odds ratio (OR), 0.38; 95%
      confidence interval (CI), 0.14 to 1.02). A significant reduction in diuretics
      (furosemide) and vasodilators (phentolamine) administration was observed in group
      F (P = 0.0085; OR, 0.22; 95% CI, 0.07 to 0.7). CONCLUSIONS: The treatment with
      high-dose fenoldopam during CPB in pediatric patients undergoing cardiac surgery
      for CHD with biventricular anatomy significantly decreased urinary levels of NGAL
      and CysC and reduced the use of diuretics and vasodilators during CPB. TRIAL
      REGISTRATION: Clinical Trial.Gov NCT00982527.

PMID- 21714858
TI  - Dengue epidemic in Malaysia: Not a predominantly urban disease anymore.
AB  - BACKGROUND: Dengue infection has been an important and serious public health
      concern in Malaysia ever since its first reported case here in 1902.
      Nevertheless, to our knowledge, no nationwide investigation has been carried out
      to determine the actual magnitude of dengue endemicity in the Malaysian
      population. In this study, we describe a cross sectional seroepidemiology study
      of dengue IgG seroprevalence in the Malaysian adult population. FINDINGS: From
      1000 subjects (35-74 years old), 91.6% subjects were found to be dengue
      seropositive. Age is found to be a significant risk factor associated with dengue
      seroposivity, where the seroprevalence increased with every 10 year increase in
      age. Nevertheless, gender and ethnicity did not have an effect. Interestingly,
      there were similar seroprevalence rates between urban and rural samples, showing
      that dengue is presently not confined to urban areas in Malaysia. CONCLUSIONS:
      High dengue IgG seropositivity found in the population is an indication that
      dengue might be endemic in Malaysia for a long time into the future. Public
      awareness, proper vector control and vigilant surveillance are critical to keep
      the infection rates low and to prevent outbreaks.

PMID- 21714859
TI  - Determinants of bed net use in children under five and household bed net
      ownership on Bioko Island, Equatorial Guinea.
AB  - BACKGROUND: As part of comprehensive malaria control strategies, the Bioko Island
      Malaria Control Project (BIMCP) distributed 110,000 long-lasting insecticide
      treated nets (LLIN) in late 2007 with the aim of providing one net for each
      sleeping area. Despite attaining initially very high levels of net coverage and
      net use, many children under five years of age did not sleep under a net by 2009,
      according to annual malaria indicator surveys. The aim of this study was to
      assess the determinants of bed net use in children under five and bed net
      ownership of the households in which they live. METHODS: Using data from annual
      cross-sectional household surveys of 2008 and 2009, we investigated factors
      associated with sleeping under a mosquito net the night prior to the survey, and
      a households owning at least one net, in all households which had at least one
      child under five years. Amongst others, caregiver's knowledge of malaria and
      household characteristics including a socio-economic score (SES), based on
      ownership of household assets, were analysed for their effect on net ownership
      and use. RESULTS: There was a decline of around 32% in the proportion of
      households that owned at least one net between 2008 and 2009. Higher household
      bed net ownership was associated with knowing how malaria was prevented and
      transmitted, having the house sprayed in the previous 12 months, having fewer
      children under five in the household, and children being sick at some point in
      the previous 14 days. Higher bed net use in children < 5 was associated with
      being sick at some point in the last 14 days prior to the survey, living in an
      urban area, more years of education of the head of the household, household
      ownership of at least one ITN (as opposed to an untreated net) and the year in
      which the survey took place. CONCLUSIONS: The big fall in bed net use from 2008
      to 2009 was attributable to the striking decline in ownership. Although ownership
      was similar in rural and urban areas, rural households were less likely to
      protect their children with bed nets. Knowledge about malaria was an important
      determinant of bed net ownership. Further research is needed to elucidate the
      decline in bed net ownership between 2008 and 2009.

PMID- 21714860
TI  - Variation in the human cannabinoid receptor CNR1 gene modulates gaze duration for
      happy faces.
AB  - BACKGROUND: From an early age, humans look longer at preferred stimuli and also
      typically look longer at facial expressions of emotion, particularly happy faces.
      Atypical gaze patterns towards social stimuli are common in autism spectrum
      conditions (ASC). However, it is unknown whether gaze fixation patterns have any
      genetic basis. In this study, we tested whether variations in the cannabinoid
      receptor 1 (CNR1) gene are associated with gaze duration towards happy faces.
      This gene was selected because CNR1 is a key component of the endocannabinoid
      system, which is involved in processing reward, and in our previous functional
      magnetic resonance imaging (fMRI) study, we found that variations in CNR1
      modulate the striatal response to happy (but not disgust) faces. The striatum is
      involved in guiding gaze to rewarding aspects of a visual scene. We aimed to
      validate and extend this result in another sample using a different technique
      (gaze tracking). METHODS: A total of 30 volunteers (13 males and 17 females) from
      the general population observed dynamic emotional expressions on a screen while
      their eye movements were recorded. They were genotyped for the identical four
      single-nucleotide polymorphisms (SNPs) in the CNR1 gene tested in our earlier
      fMRI study. RESULTS: Two SNPs (rs806377 and rs806380) were associated with
      differential gaze duration for happy (but not disgust) faces. Importantly, the
      allelic groups associated with a greater striatal response to happy faces in the
      fMRI study were associated with longer gaze duration at happy faces. CONCLUSIONS:
      These results suggest that CNR1 variations modulate the striatal function that
      underlies the perception of signals of social reward, such as happy faces. This
      suggests that CNR1 is a key element in the molecular architecture of perception
      of certain basic emotions. This may have implications for understanding
      neurodevelopmental conditions marked by atypical eye contact and facial emotion
      processing, such as ASC.

PMID- 21714861
TI  - Sustained eradication of hepatitis C virus by low-dose long-term interferon
      therapy in a renal transplant recipient with dual infection with hepatitis B and
      C viruses: a case report.
AB  - INTRODUCTION: Accelerated liver function deterioration has been recognized in
      renal transplant recipients infected with hepatitis C virus (HCV). Although
      combination therapy with interferon plus ribavirin has been established as the
      standard treatment for patients with chronic HCV, the high risk of allograft
      rejection associated with interferon therapy has greatly discouraged the clinical
      use of this regimen. In Asia, where chronic hepatitis B virus (HBV) is prevalent,
      dual infection with HBV and HCV poses an even greater challenge for clinical
      hepatologists. CASE PRESENTATION: In this article, we report the case of a 51
      year-old Taiwanese man with dual infection with HBV and HCV prior to renal
      transplantation. Low-dose interferon (3 to 6 * 106 U/week) and ribavirin (100
      mg/day to 200 mg/day) were prescribed following the reactivation of the man's HCV
      after renal transplantation. Additionally, lamivudine (100 mg/day) was
      administered concomitantly to prevent HBV reactivation. His initial serum HCV RNA
      concentration was 5.2 * 106 copies/mL (genotype 2a). After three and one-half
      years of antiviral therapy, his HCV was successfully eradicated without any
      episodes of allograft rejection. His serum HCV RNA remained negative six months
      after withdrawal from interferon and ribavirin treatment. His serum HBV DNA
      remained undetectable throughout the course of therapy. CONCLUSION: Low-dose,
      long-term interferon therapy may achieve sustained eradication of HCV in the
      renal transplant recipient with dual infection with HBV and HCV.

PMID- 21714862
TI  - Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum
      concentration of YKL-40 in Danish patients with rheumatoid arthritis and in
      healthy subjects.
AB  - INTRODUCTION: The present study investigates the association between single
      nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene and serum
      concentrations of YKL-40 in Danish patients with rheumatoid arthritis (RA) and
      healthy controls as well as the association with RA in the Danish population. The
      CHI3L1 gene is located on chromosome 1q32.1 and encodes the YKL-40 glycoprotein.
      YKL-40 concentrations are elevated in the serum of patients with RA compared to
      healthy subjects, and YKL-40 has been suggested to be an auto-antigen and may
      play a role in development of RA and in inflammation. METHODS: Eight SNPs in the
      CHI3L1 gene and promotor were genotyped in 308 patients with RA and 605 controls
      (healthy blood donors) using TaqMan allele discrimination assays. Serum
      concentrations of YKL-40 were determined by an enzyme-linked immunosorbent assay
      (ELISA). RESULTS: We found significant association between the serum
      concentrations of YKL-40 and polymorphism in the CHI3L1 gene among both patients
      with RA and controls. The g.-131(C > G) polymorphism (rs4950928) was most
      strongly associated with age adjusted serum concentrations of YKL-40 in patients
      with RA (P < 2.4e-8) and controls (P < 2.2e-16). No significant allelic- or
      genotypic association with RA was found in this Danish cohort. CONCLUSIONS: We
      suggest that the g.-131(C > G) promoter polymorphism has a substantial impact on
      serum concentrations of YKL-40 in patients with RA and healthy subjects. However,
      the polymorphism does not seem to confer risk to RA itself. The effect of CHI3L1
      polymorphism on clinical outcome or the response to treatment in patients with RA
      remains to be investigated.

PMID- 21714863
TI  - 18F-fluorodeoxyglucose positron emission tomography-positive sarcoidosis after
      chemoradiotherapy for Hodgkin's disease: a case report.
AB  - INTRODUCTION: The occurrence of granulomatous disease in the setting of Hodgkin's
      disease is rare; however, when it occurs it can pose significant clinical and
      diagnostic challenges for physicians treating these patients. CASE PRESENTATION:
      We report the case of a 33-year-old Caucasian woman of Mediterranean descent with
      newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography
      (PET)/computed tomography (CT) scan-positive, early-stage Hodgkin's disease
      involving the cervical nodes who, despite having an excellent clinical response
      to chemotherapy, had a persistent 18F-FDG PET scan-positive study, which was
      suggestive of residual or progressive disease. A subsequent biopsy of her post
      chemotherapy PET-positive nodes demonstrated sarcoidosis with no evidence of
      Hodgkin's disease. CONCLUSION: This case highlights the fact that abnormalities
      observed on posttherapy PET/CT scans in patients with Hodgkin's disease are not
      always due to residual or progressive disease. An association between Hodgkin's
      disease and/or its treatment with an increased incidence of granulomatous disease
      appears to exist. Certain patterns of 18F-FDG uptake observed on PET/CT scans may
      suggest other pathologies, such as granulomatous inflammation, and because of the
      significant differences in prognosis and management, clinicians should maintain a
      low threshold of confidence for basing their diagnosis on histopathological
      evaluations when PET/CT results appear to be incongruent with the patient's
      clinical response.

PMID- 21714864
TI  - Renal cell carcinoma metastasizing to solitary fibrous tumor of the pleura: a
      case report.
AB  - INTRODUCTION: A tumor metastasizing to another malignancy is an uncommon
      phenomenon. Since it was first described in 1902, there have been fewer than 200
      cases reported in the literature, with lung cancer metastasizing to renal cell
      carcinoma being the most frequently described pattern. Here we report a case of a
      solitary fibrous tumor of the lung acting as the recipient for a renal cell
      carcinoma. To our knowledge, this is the first reported case of such a
      combination and the second case involving a solitary fibrous tumor. CASE
      PRESENTATION: A 58-year-old Caucasian man who developed a persistent dry cough
      presented to our hospital. Imaging studies revealed a large pleural-based mass in
      the left lung. A biopsy of the mass showed a spindle-cell lesion consistent with
      a solitary fibrous tumor. The patient underwent surgical excision of the 13 cm
      mass. The pathological examination confirmed the diagnosis of a solitary fibrous
      tumor but also demonstrated discrete foci of metastatic renal cell carcinoma.
      Until that point, a primary renal cell carcinoma tissue diagnosis had not been
      made and the initial radiological work-up was inconclusive. CONCLUSION: Awareness
      of the unusual phenomenon of tumor-to-tumor metastasis is important for
      practicing surgical pathologists, particularly in the evaluation of a mass lesion
      showing bimodal histology. This case also highlights the importance of careful
      examination of surgical specimens, as minute and unusual findings can direct
      patient care.

PMID- 21714865
TI  - Risk based culling for highly infectious diseases of livestock.
AB  - The control of highly infectious diseases of livestock such as classical swine
      fever, foot-and-mouth disease, and avian influenza is fraught with ethical,
      economic, and public health dilemmas. Attempts to control outbreaks of these
      pathogens rely on massive culling of infected farms, and farms deemed to be at
      risk of infection. Conventional approaches usually involve the preventive culling
      of all farms within a certain radius of an infected farm. Here we propose a novel
      culling strategy that is based on the idea that farms that have the highest
      expected number of secondary infections should be culled first. We show that, in
      comparison with conventional approaches (ring culling), our new method of risk
      based culling can reduce the total number of farms that need to be culled, the
      number of culled infected farms (and thus the expected number of human infections
      in case of a zoonosis), and the duration of the epidemic. Our novel risk based
      culling strategy requires three pieces of information, viz. the location of all
      farms in the area at risk, the moments when infected farms are detected, and an
      estimate of the distance-dependent probability of transmission.

PMID- 21714866
TI  - Colonization factors of Campylobacter jejuni in the chicken gut.
AB  - Campylobacter contaminated broiler chicken meat is an important source of
      foodborne gastroenteritis and poses a serious health burden in industrialized
      countries. Broiler chickens are commonly regarded as a natural host for this
      zoonotic pathogen and infected birds carry a very high C. jejuni load in their
      gastrointestinal tract, especially the ceca. This eventually results in
      contaminated carcasses during processing. Current intervention methods fail to
      reduce the colonization of broiler chicks by C. jejuni due to an incomplete
      understanding on the interaction between C. jejuni and its avian host. Clearly,
      C. jejuni developed several survival and colonization mechanisms which are
      responsible for its highly adapted nature to the chicken host. But how these
      mechanisms interact with one another, leading to persistent, high-level cecal
      colonization remains largely obscure. A plethora of mutagenesis studies in the
      past few years resulted in the identification of several of the genes and
      proteins of C. jejuni involved in different aspects of the cellular response of
      this bacterium in the chicken gut. In this review, a thorough, up-to-date
      overview will be given of the survival mechanisms and colonization factors of C.
      jejuni identified to date. These factors may contribute to our understanding on
      how C. jejuni survival and colonization in chicks is mediated, as well as provide
      potential targets for effective subunit vaccine development.

PMID- 21714867
TI  - A metabolic model of the mitochondrion and its use in modelling diseases of the
      tricarboxylic acid cycle.
AB  - BACKGROUND: Mitochondria are a vital component of eukaryotic cells and their
      dysfunction is implicated in a large number of metabolic, degenerative and age
      related human diseases. The mechanism or these disorders can be difficult to
      elucidate due to the inherent complexity of mitochondrial metabolism. To
      understand how mitochondrial metabolic dysfunction contributes to these diseases,
      a metabolic model of a human heart mitochondrion was created. RESULTS: A new
      model of mitochondrial metabolism was built on the principle of metabolite
      availability using MitoMiner, a mitochondrial proteomics database, to evaluate
      the subcellular localisation of reactions that have evidence for mitochondrial
      localisation. Extensive curation and manual refinement was used to create a model
      called iAS253, containing 253 reactions, 245 metabolites and 89 transport steps
      across the inner mitochondrial membrane. To demonstrate the predictive abilities
      of the model, flux balance analysis was used to calculate metabolite fluxes under
      normal conditions and to simulate three metabolic disorders that affect the TCA
      cycle: fumarase deficiency, succinate dehydrogenase deficiency and alpha
      ketoglutarate dehydrogenase deficiency. CONCLUSION: The results of simulations
      using the new model corresponded closely with phenotypic data under normal
      conditions and provided insight into the complicated and unintuitive phenotypes
      of the three disorders, including the effect of interventions that may be of
      therapeutic benefit, such as low glucose diets or amino acid supplements. The
      model offers the ability to investigate other mitochondrial disorders and can
      provide the framework for the integration of experimental data in future studies.

PMID- 21714868
TI  - phenosim--A software to simulate phenotypes for testing in genome-wide
      association studies.
AB  - BACKGROUND: There is a great interest in understanding the genetic architecture
      of complex traits in natural populations. Genome-wide association studies (GWAS)
      are becoming routine in human, animal and plant genetics to understand the
      connection between naturally occurring genotypic and phenotypic variation.
      Coalescent simulations are commonly used in population genetics to simulate
      genotypes under different parameters and demographic models. RESULTS: Here, we
      present phenosim, a software to add a phenotype to genotypes generated in time
      efficient coalescent simulations. Both qualitative and quantitative phenotypes
      can be generated and it is possible to partition phenotypic variation between
      additive effects and epistatic interactions between causal variants. The output
      formats of phenosim are directly usable as input for different GWAS tools. The
      applicability of phenosim is shown by simulating a genome-wide association study
      in Arabidopsis thaliana. CONCLUSIONS: By using the coalescent approach to
      generate genotypes and phenosim to add phenotypes, the data sets can be used to
      assess the influence of various factors such as demography, genetic architecture
      or selection on the statistical power of association methods to detect causal
      genetic variants under a wide variety of population genetic scenarios. phenosim
      is freely available from the authors' website http://evoplant.uni-hohenheim.de.

PMID- 21714869
TI  - MicroRNA preparations from individual monogenean Gyrodactylus salaris-a
      comparison of six commercially available totalRNA extraction kits.
AB  - BACKGROUND: Describing and evaluating miRNA inventories with Next Generation
      Sequencing is a goal of scientists from a wide range of fields. It requires high
      purity, high quality, and high yield RNA extractions that do not only contain
      abundant ribosomal RNAs but are also enriched in miRNAs. Here we compare 6
      disparate and commercially available totalRNA extraction kits for their
      suitability for miRNA-preparations from Gyrodactylus salaris, an important but
      small (500 MUm in length) monogenean pathogen of Norwegian Atlantic salmon (Salmo
      salar). FINDINGS: We evaluated 1 salt precipitation method (MasterPureTM Complete
      RNA Purification Kit, Epicentre), 2 Phenol based extraction methods (mirVana Kit,
      Ambion, and Trizol Plus Kit, Invitrogen), 1 paramagnetic bead extraction method
      (RNA Tissue kit, GeneMole) and 2 purification methods based on spin column
      chromatography using a proprietary resin as separation matrix (Phenol-free Total
      RNA Purification Kit, Amresco, and ZR MicroPrep Kit, Zymo Research). The quality
      of the extractions from 1, 10 and 100 individuals, respectively, was assessed in
      terms of totalRNA yield, RNA integrity, and smallRNA and miRNA yield. The 6 RNA
      extraction methods yielded considerably different total RNA extracts, with
      striking differences in low molecular weight RNA yield. The Phenol-free Total RNA
      Purification Kit (Amresco) showed the highest totalRNA yield, but the best
      miRNA/totalRNA ratio was obtained with the ZR MicroPrep Kit (Zymo Research). It
      was not possible to extract electrophoretically detectable miRNAs from
      Gyrodactylus salaris with the RNA Tissue Kit (GeneMole) or the Trizol Plus Kit
      (Invitrogen). CONCLUSIONS: We present an optimized extraction protocol for single
      and small numbers of Gyrodactylus salaris from infected Atlantic salmon that
      delivers a totalRNA yield suitable for downstream next generation sequencing
      analyses of miRNA. Two of the six tested totalRNA kits/methods were not suitable
      for the extraction of miRNAs from Gyrodactylus salaris.

PMID- 21714870
TI  - Evaluating professionalism in medical undergraduates using selected response
      questions: findings from an item response modelling study.
AB  - BACKGROUND: Professionalism is a difficult construct to define in medical
      students but aspects of this concept may be important in predicting the risk of
      postgraduate misconduct. For this reason attempts are being made to evaluate
      medical students' professionalism. This study investigated the psychometric
      properties of Selected Response Questions (SRQs) relating to the theme of
      professional conduct and ethics comparing them with two sets of control items:
      those testing pure knowledge of anatomy, and; items evaluating the ability to
      integrate and apply knowledge ("skills"). The performance of students on the SRQs
      was also compared with two external measures estimating aspects of
      professionalism in students; peer ratings of professionalism and their
      Conscientiousness Index, an objective measure of behaviours at medical school.
      METHODS: Item Response Theory (IRT) was used to analyse both question and student
      performance for SRQs relating to knowledge of professionalism, pure anatomy and
      skills. The relative difficulties, discrimination and 'guessabilities' of each
      theme of question were compared with each other using Analysis of Variance
      (ANOVA). Student performance on each topic was compared with the measures of
      conscientiousness and professionalism using parametric and non-parametric tests
      as appropriate. A post-hoc analysis of power for the IRT modelling was conducted
      using a Monte Carlo simulation. RESULTS: Professionalism items were less
      difficult compared to the anatomy and skills SRQs, poorer at discriminating
      between candidates and more erratically answered when compared to anatomy
      questions. Moreover professionalism item performance was uncorrelated with the
      standardised Conscientiousness Index scores (rho = 0.009, p = 0.90). In contrast
      there were modest but significant correlations between standardised
      Conscientiousness Index scores and performance at anatomy items (rho = 0.20, p =
      0.006) though not skills (rho = .11, p = .1). Likewise, students with high peer
      ratings for professionalism had superior performance on anatomy SRQs but not
      professionalism themed questions. A trend of borderline significance (p = .07)
      was observed for performance on skills SRQs and professionalism nomination
      status. CONCLUSIONS: SRQs related to professionalism are likely to have
      relatively poor psychometric properties and lack associations with other
      constructs associated with undergraduate professional behaviour. The findings
      suggest that such questions should not be included in undergraduate examinations
      and may raise issues with the introduction of Situational Judgement Tests into
      Foundation Years selection.

PMID- 21714871
TI  - Spermatocytic seminoma at the National Institute of Oncology in Morocco.
AB  - BACKGROUND: Spermatocytic seminoma (SS) is a distinct testicular germ cell tumor,
      representing less than 1% of testicular cancers. The clinical features that
      distinguish ss from classical seminoma are an older age at presentation and a
      reduced propensity to metastasize. The aim of our work is to underline the
      epidemiological, clinical, histological, therapeutical and prognostic features of
      this tumor. FINDINGS: A retrospective analysis of patients referred to the
      national institute of oncology with seminoma, identified from the institutional
      tumor registry, between January 1996 and February 2009, was performed.
      Information reviewed included demographics, clinical, pathological staging,
      surgical management, adjuvant treatment and last follow-up. We studied four cases
      of spermatocytic seminoma, which represented 1% of testicular tumor and 6,4% of
      all seminoma treated at our institution during the study period. Median age at
      diagnosis was 45 years (range: 42-48). Mean delay before consulting was 9 months
      and the mean tumor size was 13,75 cm (10-18 cm). No patient had a history of
      maldescended testis. The main clinical complaint was unilateral testis mass with
      low progression. Pathology showed that tumors had a polymorphic appearance with
      small, intermediate and large cells. In all cases, the tumor was limited to the
      testis. immunohistochemical studies showed that tumors were negative for all the
      classical antibodies tested (LCA, cytokeratins, PLAP, lymphoid markers, CD117).
      Thoraco-abdomino-pelvic CT scan and tumor markers (AFP and hCG) were normal. All
      patients were Stage I. Treatment consisted on an orchidectomy associated with
      adjuvant radiotherapy in one patient. After a median follow-up of 6 years ranging
      from 2 to 15 years, we did not note any relapse or metastasis. CONCLUSION: The
      diagnosis of spermatocytic seminoma must be considered in all patients aged of
      more than 50 with testicular tumor. With only three cases of metastatic disease
      confirmed in the literature, this is a subgroup of patients in whom radiotherapy
      can safely be omitted.

PMID- 21714872
TI  - Differences in bioactivity between human insulin and insulin analogues approved
      for therapeutic use- compilation of reports from the past 20 years.
AB  - In order to provide comprehensive information on the differences in bioactivity
      between human insulin and insulin analogues, published in vitro comparisons of
      human insulin and the rapid acting analogues insulin lispro (Humalog(r)), insulin
      aspart ( NovoRapid(r)), insulin glulisine (Apidra(r)), and the slow acting
      analogues insulin glargine (Lantus(r)), and insulin detemir (Levemir(r)) were
      gathered from the past 20 years (except for receptor binding studies). A total of
      50 reports were retrieved, with great heterogeneity among study methodology.
      However, various differences in bioactivity compared to human insulin were
      obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis,
      intracellular signalling, thrombocyte function, protein degradation). Whether or
      not these differences have clinical bearings (and among which patient
      populations) remains to be determined.

PMID- 21714873
TI  - Periductal stromal sarcoma in a child: a case report.
AB  - INTRODUCTION: Periductal stromal sarcoma is an extremely rare malignant
      fibroepithelial tumor of the breast which is characterized by its biphasic
      histology with benign ductal elements and a sarcomatous stroma made of spindle
      cells and lacking phyllodes architecture. Its therapeutic management is based on
      wide surgery with free margins. Adjuvant therapies are not needed. Periductal
      stromal sarcoma may evolve into a phyllodes tumor with time, as well as a
      specific soft-tissue sarcoma. To the best of our knowledge, this tumor has never
      been described in a child. CASE PRESENTATION: A 14-year-old Arabic boy was
      presented to our hospital one year ago with a nodule of the right breast that was
      gradually increasing in size without signs of inflammation. The histological
      examination after lumpectomy revealed a periductal stromal sarcoma with free
      surgical margins. No adjuvant treatment was given. At 50 months of close follow
      up, no recurrence was observed. CONCLUSION: Periductal stromal sarcoma in a child
      is a very rare disease which has the same indolent behavior as it does in adults.
      Therefore, close follow-up is required.

PMID- 21714874
TI  - Serotonin transporter gene polymorphism may be associated with functional
      dyspepsia in a Japanese population.
AB  - BACKGROUND: Although familial clustering of functional dyspepsia (FD) has been
      reported, the role of genetics in the susceptibility to FD is still not well
      understood. In the present study, the association between serotonin transporter
      (SERT) gene (SLC6A4) polymorphism and FD was explored. METHODS: Subjects were
      divided into either a postprandial distress syndrome (PDS) group or an epigastric
      pain syndrome (EPS) group according to the Rome III criteria. The healthy
      controls were those who had visited a hospital for an annual health check-up. The
      presence of the SLC6A4 promoter polymorphism, 5-hydroxytryptamin transporter gene
      linked polymorphic region (5-HTTLPR), was then evaluated, and logistic regression
      analysis was used to test all variables. RESULTS: The 5-HTTLPR genotype
      distribution was 448 SS, 174 SL, and 24 LL in controls and 30 SS, 20 SL, and 3 LL
      in FD subjects. No significant correlation was found between the 5-HTTLPR
      genotype and FD. When the genotypes and subtypes of FD were exploratory
      evaluated, the SL genotype was significantly associated with PDS [odds ratio (OR)
      = 2.24, 95% confidence interval (CI); 1.16-4.32, P = 0.034 after Bonferroni
      correction] compared to the SS genotype adjusted for sex and age. Comparison of
      the SS genotype with the SL/LL genotype also showed a significant association of
      genotype with PDS (OR = 2.32, 95% CI; 1.23-4.37, P = 0.009). CONCLUSION: The
      present results suggest that 5-HTTLPR L allele may influence the susceptibility
      to PDS.

PMID- 21714875
TI  - Male breast cancer: a report of 127 cases at a Moroccan institution.
AB  - BACKGROUND: Male breast cancer (MBC) is a rare disease representing less than 1%
      of all malignancies in men and only 1% of all incident breast cancers. Our study
      details clinico-pathological features, treatments and prognostic factors in a
      large Moroccan cohort. FINDINGS: One hundred and twenty-seven patients were
      collected from 1985 to 2007 at the National Institute of Oncology in Rabat,
      Morocco.Median age was 62 years and median time for consultation 28 months. The
      main clinical complaint was a mass beneath the areola in 93, 5% of the cases.
      Most patients have an advanced disease. Ninety-one percent of tumors were ductal
      carcinomas.Management consisted especially of radical mastectomy; followed by
      adjuvant radiotherapy and hormonal therapy with or without chemotherapy. The
      median of follow-up was 30 months. The evolution has been characterized by local
      recurrence; in twenty two cases (17% of all patients). Metastasis occurred in 41
      cases (32% of all patients). The site of metastasis was the bone in twenty cases;
      lung in twelve cases; liver in seven case; liver and skin in one case and pleura
      and skin in one case. CONCLUSION: Male breast cancer has many similarities to
      breast cancer in women, but there are distinct features that should be
      appreciated. Future research for better understanding of this disease at national
      or international level are needed to improve the management and prognosis of male
      patients.

PMID- 21714876
TI  - Changes in smoking prevalence among U.S. adults by state and region: Estimates
      from the Tobacco Use Supplement to the Current Population Survey, 1992-2007.
AB  - BACKGROUND: Tobacco control policies at the state level have been a critical
      impetus for reduction in smoking prevalence. We examine the association between
      recent changes in smoking prevalence and state-specific tobacco control policies
      and activities in the entire U.S. METHODS: We analyzed the 1992-93, 1998-99, and
      2006-07 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) by
      state and two indices of state tobacco control policies or activities [initial
      outcome index (IOI) and the strength of tobacco control (SOTC) index] measured in
      1998-1999. The IOI reflects cigarette excise taxes and indoor air legislation,
      whereas the SOTC reflects tobacco control program resources and capacity. Pearson
      Correlation coefficient between the proportionate change in smoking prevalence
      from 1992-93 to 2006-07 and indices of tobacco control activities or programs was
      the main outcome measure. RESULTS: Smoking prevalence decreased from 1992-93 to
      2006-07 in both men and women in all states except Wyoming, where no reduction
      was observed among men, and only a 6.9% relative reduction among women. The
      percentage reductions in smoking in men and women respectively were the largest
      in the West (average decrease of 28.5% and 33.3%) and the smallest in the Midwest
      (18.6% and 20.3%), although there were notable exceptions to this pattern. The
      decline in smoking prevalence by state was correlated with the state's IOI in
      both women and men (r = -0.49, p < 0.001; r = -0.31, p = 0.03; respectively) and
      with state's SOTC index in women(r = -0.30, p = 0.03 0), but not men (r = -0.21,
      p = 0.14). CONCLUSION: State level policies on cigarette excise taxes and indoor
      air legislation correlate strongly with reductions in smoking prevalence since
      1992. Strengthening and systematically implementing these policies could greatly
      accelerate further reductions in smoking.

PMID- 21714877
TI  - Cost of individual peer counselling for the promotion of exclusive breastfeeding
      in Uganda.
AB  - BACKGROUND: Exclusive breastfeeding (EBF) for 6 months is the recommended form of
      infant feeding. Support of mothers through individual peer counselling has been
      proved to be effective in increasing exclusive breastfeeding prevalence. We
      present a costing study of an individual peer support intervention in Uganda,
      whose objective was to raise exclusive breastfeeding rates at 3 months of age.
      METHODS: We costed the peer support intervention, which was offered to 406
      breastfeeding mothers in Uganda. The average number of counselling visits was
      about 6 per woman. Annual financial and economic costs were collected in 2005
      2008. Estimates were made of total project costs, average costs per mother
      counselled and average costs per peer counselling visit. Alternative intervention
      packages were explored in the sensitivity analysis. We also estimated the
      resources required to fund the scale up to district level, of a breastfeeding
      intervention programme within a public health sector model. RESULTS: Annual
      project costs were estimated to be US$56,308. The largest cost component was peer
      supporter supervision, which accounted for over 50% of total project costs. The
      cost per mother counselled was US$139 and the cost per visit was US$26. The cost
      per week of EBF was estimated to be US$15 at 12 weeks post partum. We estimated
      that implementing an alternative package modelled on routine public health sector
      programmes can potentially reduce costs by over 60%. Based on the calculated
      average costs and annual births, scaling up modelled costs to district level
      would cost the public sector an additional US$1,813,000. CONCLUSION: Exclusive
      breastfeeding promotion in sub-Saharan Africa is feasible and can be implemented
      at a sustainable cost. The results of this study can be incorporated in cost
      effectiveness analyses of exclusive breastfeeding promotion programmes in sub
      Saharan Africa.

PMID- 21714878
TI  - Shortening of treatment duration in patients with chronic hepatitis C genotype 2
      and 3 - impact of ribavirin dose - a randomized multicentre trial.
AB  - BACKGROUND: Chronic hepatitis C (CHC) Patients, infected with genotype (GT) 2 or
      3 are treated with Peg-IFN and ribavirin (RBV) (800 mg/day) for 24 weeks.
      Treatment duration can be shortened to 12-16 weeks if a higher dose of RBV
      (1.000/1.200 mg/day) was used without considerable loss of responsiveness or
      increased risk of relapse. Previously we have shown that in patients with CHC, GT
      2/3 RBV can be reduced to 400 mg/day if administered for 24 weeks without an
      increase in relapse rates. Therefore we investigated the efficacy of a reduced
      RBV dosage of 400 mg/day with shorter treatment duration (16 weeks). METHODS:
      Treatment naive patients with CHC, GT 2/3 were randomized to receive 180 MUg
      peginterferonalpha2a/week in combination with either 800 (group C) or 400 mg/d
      (group D) for 16 weeks. The primary endpoint was SVR. RESULTS: 12 months after
      the first patient was randomized a inferior outcome of group D as compared to
      group C was noted, therefore the study was terminated. At study termination 89
      patients were enrolled (group C: 31, D: 51). The SVR rate was statistically
      different in the two study groups with 51.6% in group C and 28.4% in group D (p =
      0.038). Patients with low viral load had higher SVR rates (C: 67%, D: 33%) than
      those with high viral load (C: 33%, D: 21%). CONCLUSION: Both treatment duration
      and the dose of RBV play a major role to optimize outcome of patients with GT3.
      If one intends to shorten the treatment weight based RBV dose should be used, if
      lower RBV doses are used patients should be treated for at least 24 weeks as. A
      treatment regimen with a reduced RBV dosage and shortened treatment duration is
      associated with low SVR rates due to high relapse rates. TRIAL REGISTRATION:
      NCT01258101.

PMID- 21714879
TI  - LigaSure ImpactTM versus conventional dissection technique in pylorus-preserving
      pancreatoduodenectomy in clinical suspicion of cancerous tumours on the head of
      the pancreas: study protocol for a randomised controlled trial.
AB  - BACKGROUND: The pp-Whipple procedure requires extensive preparation. The
      conventional preparation technique is done with scissors for dissection and
      ligatures, and with clips and sutures for hemostasis. This procedure is very time
      consuming and requires numerous changes of instruments. The LigaSureTM device
      allows dissection and hemostasis for preparation with one instrument. Up to now
      there has been no comparison of the two techniques with regard to operating time
      and the patients' outcome. It is still unclear which technique has the optimal
      benefit/risk ratio for the patient. METHODS/DESIGN: A single-center, randomized,
      single-blinded, controlled superiority trial to compare two different techniques
      for dissection in a pp-Whipple procedure. 102 patients will be included and
      randomized pre-operatively. All patients aged 18 years or older scheduled for
      primary elective pp-Whipple procedure who signed the informed consent will be
      included. The primary endpoint is the operating time of the randomized technique.
      Control Intervention: Conventional dissection technique; experimental
      intervention: LigaSureTM dissection technique. Duration of study: Approximately
      15 months; follow up time: 3 years. The trial is registered at German
      ClinicalTrials Register (DRKS00000166).

PMID- 21714880
TI  - Premature ovarian failure in a woman with a balanced 15;21 translocation: a case
      report.
AB  - INTRODUCTION: A case of premature ovarian failure with concomitant findings of
      Robertsonian translocation between 15 and 21 chromosomes is reported here. The
      aforementioned karyotypic aberration has not been reported in the context of
      premature ovarian failure to date. CASE PRESENTATION: We present a case of
      premature ovarian failure in a 27-year-old infertile Kurdish Iranian woman with a
      Robertsonian 15;21 translocation. CONCLUSIONS: The diagnosis of premature ovarian
      failure of unknown etiology, but with karyotypic evidence of a balanced autosomal
      translocation, suggests the possible role of autosomal genes in the pathogenesis
      of ovarian follicular attrition.

PMID- 21714881
TI  - Maternal near-miss in a rural hospital in Sudan.
AB  - BACKGROUND: Investigation of maternal near-miss is a useful complement to the
      investigation of maternal mortality with the aim of meeting the United Nations'
      fifth Millennium Development Goal. The present study was conducted to investigate
      the frequency of near-miss events, to calculate the mortality index for each
      event and to compare the socio-demographic and obstetrical data (age, parity,
      gestational age, education and antenatal care) of the near-miss cases with
      maternal deaths. METHODS: Near-miss cases and events (hemorrhage, infection,
      hypertensive disorders, anemia and dystocia), maternal deaths and their causes
      were retrospectively reviewed and the mortality index for each event was
      calculated in Kassala Hospital, eastern Sudan over a 2-year period, from January
      2008 to December 2010. Disease-specific criteria were applied for these events.
      RESULTS: There were 9578 deliveries, 205 near-miss cases, 228 near-miss events
      and 40 maternal deaths. Maternal near-miss and maternal mortality ratio were
      22.1/1000 live births and 432/100 000 live births, respectively. Hemorrhage
      accounted for the most common event (40.8%), followed by infection (21.5%),
      hypertensive disorders (18.0%), anemia (11.8%) and dystocia (7.9%). The mortality
      index were 22.2%, 10.0%, 10.0%, 8.8% and 2.4% for infection, dystocia, anemia,
      hemorrhage and hypertensive disorders, respectively. CONCLUSION: There is a high
      frequency of maternal morbidity and mortality at the level of this facility.
      Therefore maternal health policy needs to be concerned not only with averting the
      loss of life, but also with preventing or ameliorating maternal-near miss events
      (hemorrhage, infections, hypertension and anemia) at all care levels including
      primary level.

PMID- 21714882
TI  - Native valve endocarditis due to Micrococcus luteus: a case report and review of
      the literature.
AB  - INTRODUCTION: Micrococcus luteus endocarditis is a rare case of infective
      endocarditis. A total of 17 cases of infective endocarditis due to M luteus have
      been reported in the literature to date, all involving prosthetic valves. To the
      best of our knowledge, we describe the first case of native aortic valve M luteus
      endocarditis in an immunosuppressed patient in this report. CASE REPORT: A 74
      year-old Greek-Cypriot woman was admitted to our Internal Medicine Clinic due to
      fever and malaise and the diagnosis of aortic valve M luteus endocarditis was
      made. She was immunosuppressed due to methotrexate and steroid treatment. Our
      patient was unsuccessfully treated with vancomycin, gentamicin and rifampicin for
      four weeks. The aortic valve was replaced and she was discharged in good
      condition. CONCLUSIONS: Prosthetic infective endocarditis due to M luteus is
      rare. To the best of our knowledge, we report the first case in the literature
      involving a native valve.

PMID- 21714884
TI  - Stress-induced hemorrhagic gastric ulcer after successful Helicobacter pylori
      eradication: two case reports.
AB  - INTRODUCTION: Helicobacter pylori infection is a major cause of gastric ulcers,
      and Helicobacter pylori eradication drastically reduces ulcer recurrence. It has
      been reported, however, that severe physical stress is closely associated with
      gastric ulceration even in Helicobacter pylori -negative patients. CASE
      PRESENTATION: We report the cases of a 47-year-old Japanese man and a 69-year-old
      Japanese man who developed psychological stress-induced hemorrhagic gastric
      ulcers, in both of whom Helicobacter pylori had been successfully eradicated.
      CONCLUSION: Our cases strongly suggest that not only physical but also
      psychological stress is still an important pathogenic factor for peptic
      ulceration and accordingly that physicians should pay attention to the possible
      presence of psychological stress in the management of patients with peptic
      ulcers.

PMID- 21714883
TI  - Primary care practice-based care management for chronically ill patients
      (PraCMan): study protocol for a cluster randomized controlled trial
      [ISRCTN56104508].
AB  - BACKGROUND: Care management programmes are an effective approach to care for high
      risk patients with complex care needs resulting from multiple co-occurring
      medical and non-medical conditions. These patients are likely to be hospitalized
      for a potentially "avoidable" cause. Nurse-led care management programmes for
      high risk elderly patients showed promising results. Care management programmes
      based on health care assistants (HCAs) targeting adult patients with a high risk
      of hospitalisation may be an innovative approach to deliver cost-efficient
      intensified care to patients most in need. METHODS/DESIGN: PraCMan is a cluster
      randomized controlled trial with primary care practices as unit of randomisation.
      The study evaluates a complex primary care practice-based care management of
      patients at high risk for future hospitalizations. Eligible patients either
      suffer from type 2 diabetes mellitus, chronic obstructive pulmonary disease,
      chronic heart failure or any combination. Patients with a high likelihood of
      hospitalization within the following 12 months (based on insurance data) will be
      included in the trial. During 12 months of intervention patients of the care
      management group receive comprehensive assessment of medical and non-medical
      needs and resources as well as regular structured monitoring of symptoms.
      Assessment and monitoring will be performed by trained HCAs from the
      participating practices. Additionally, patients will receive written information,
      symptom diaries, action plans and a medication plan to improve self-management
      capabilities. This intervention is addition to usual care. Patients from the
      control group receive usual care. Primary outcome is the number of all-cause
      hospitalizations at 12 months follow-up, assessed by insurance claims data.
      Secondary outcomes are health-related quality of life (SF12, EQ5D), quality of
      chronic illness care (PACIC), health care utilisation and costs, medication
      adherence (MARS), depression status and severity (PHQ-9), self-management
      capabilities and clinical parameters. Data collection will be performed at
      baseline, 12 and 24 months (12 months post-intervention). DISCUSSION: Practice
      based care management for high risk individuals involving trained HCAs appears to
      be a promising approach to face the needs of an aging population with increasing
      care demands.

PMID- 21714885
TI  - Attention problems and language development in preterm low-birth-weight children:
      cross-lagged relations from 18 to 36 months.
AB  - BACKGROUND: Research has highlighted a series of persistent deficits in cognitive
      ability in preterm low-birth-weight children. Language and attention problems are
      among these deficits, although the nature of the relation between attention and
      language in early development is not well known. This study represents a
      preliminary attempt to shed light on the relations between attention problems and
      language development in preterm low-birth-weight children. METHODS: The aim of
      this study was to analyse reciprocal influences between language and attention
      problems from 18 to 36 months. We used maternal reports on attention problems and
      language ability referring to a sample of 1288 premature low-birth-weight
      infants, collected as part of the Norwegian Mother and Child Cohort Study (MoBa).
      A sample of children born full-term was used as the control group (N = 37010).
      Cross-lagged panel analyses were carried out to study reciprocal influences
      between attention problems and language. RESULTS: Language ability at 18 months
      did not significantly predict attention problems at 36 months, adjusting for
      attention problems at 18 months. Attention problems at 18 months significantly
      predicted changes in language ability from 18 to 36 months, pointing to a
      precursor role of attention in relation to language in children born preterm.
      Gender, age corrected for prematurity, and mother's education emerged as
      important covariates. CONCLUSIONS: Preliminary evidence was found for a precursor
      role of early attention problems in relation to language in prematurity. This
      finding can contribute to a better understanding of the developmental pathways of
      attention and language and lead to better management of unfavourable outcomes
      associated with co-morbid attention and language difficulties.

PMID- 21714886
TI  - An unusual case of autoimmune pancreatitis presenting as pancreatic mass and
      obstructive jaundice: a case report and review of the literature.
AB  - BACKGROUND: Autoimmune pancreatitis is a rare chronic inflammatory pancreatic
      disease that is increasingly being diagnosed worldwide. As a result of overlap in
      clinical and radiological features, it is often misdiagnosed as pancreatic
      cancer. We report the case of a patient with autoimmune pancreatitis that was
      initially misdiagnosed as pancreatic cancer. CASE PRESENTATION: A 31-year-old
      Caucasian man presented to our hospital with epigastric pain, jaundice and weight
      loss. His CA 19-9 level was elevated, and computed tomography and endoscopic
      ultrasound revealed a pancreatic head mass abutting the portal vein. Endoscopic
      retrograde cholangiopancreaticography showed narrowing of the biliary duct and
      poor visualization of the pancreatic duct. Fine-needle aspiration biopsy revealed
      atypical ductal epithelial cells, which raised clinical suspicion of
      adenocarcinoma. Because of the patient's unusual age for the onset of pancreatic
      cancer and the acuity of his symptoms, he was referred to a tertiary care center
      for further evaluation. His immunoglobulin G4 antibody level was 365 mg/dL, and
      repeat computed tomography showed features typical of autoimmune pancreatitis.
      The patient's symptoms resolved with corticosteroid therapy. CONCLUSION:
      Autoimmune pancreatitis is a rare disease with an excellent response to
      corticosteroid therapy. Its unique histological appearance and response to
      corticosteroid therapy can reduce unnecessary surgical procedures. A thorough
      evaluation by a multidisciplinary team is important in rendering the diagnosis of
      autoimmune pancreatitis.

PMID- 21714887
TI  - Different metastasis promotive potency of small G-proteins RalA and RalB in in
      vivo hamster tumor model.
AB  - BACKGROUND: Previously we have shown that oncogenic Ha-Ras stimulated in vivo
      metastasis through RalGEF-Ral signaling. RalA and RalB are highly homologous
      small G proteins belonging to Ras superfamily. They can be activated by Ras
      RalGEF signaling pathway and influence cellular growth and survival, motility,
      vesicular transport and tumor progression in humans and in animal models. Here we
      first time compared the influence of RalA and RalB on tumorigenic, invasive and
      metastatic properties of RSV transformed hamster fibroblasts. METHODS: Retroviral
      vectors encoding activated forms or effector mutants of RalA or RalB proteins
      were introduced into the low metastatic HET-SR cell line. Tumor growth and
      spontaneous metastatic activity (SMA) were evaluated on immunocompetent hamsters
      after subcutaneous injection of cells. The biological properties of cells,
      including proliferation, clonogenicity, migration and invasion were determined
      using MTT, wound healing, colony formation and Boyden chamber assays
      respectively. Protein expression and phosphorylation was detected by Westen blot
      analysis. Extracellular proteinases activity was assessed by substrate-specific
      zymography. RESULTS: We have showed that although both Ral proteins stimulated
      SMA, RalB was more effective in metastasis stimulation in vivo as well as in
      potentiating of directed movement and invasion in vitro. Simultaneous expression
      of active RalA and RalB didn't give synergetic effect on metastasis formation.
      RalB activity decreased expression of Caveolin-1, while active RalA stimulated
      MMP-1 and uPA proteolytic activity, as well as CD24 expression. Both Ral proteins
      were capable of Cyclin D1 upregulation, JNK1 kinase activation, and stimulation
      of colony growth and motility. Among three main RalB effectors (RalBP1, exocyst
      complex and PLD1), PLD1 was essential for RalB-dependent metastasis stimulation.
      CONCLUSIONS: Presented results are the first data on direct comparison of RalA
      and RalB impact as well as of RalA/RalB simultaneous expression influence on in
      vivo cell metastatic activity. We showed that RalB activation significantly more
      than RalA stimulates SMA. This property correlates with the ability of RalB to
      stimulate in vitro invasion and serum directed cell movement. We also found that
      RalB-PLD1 interaction is necessary for the acquisition of RalB-dependent high
      metastatic cell phenotype. These findings contribute to the identification of
      molecular mechanisms of metastasis and tumor progression.

PMID- 21714888
TI  - Acute abdomen caused by bladder rupture attributable to neurogenic bladder
      dysfunction following a stroke: a case report.
AB  - INTRODUCTION: Spontaneous bladder rupture is a rare and serious event with high
      mortality. It is not often considered in the patient presenting with peritonitis.
      This often leads to delays in diagnosis. There are very few case reports of true
      spontaneous rupture in the literature. This is the first such reported case in
      which bladder rupture was attributable to neurogenic bladder dysfunction
      following a stroke. CASE PRESENTATION: We report the case of a 67-year-old
      Caucasian man who presented with lower abdominal pain and a peritonitic abdomen.
      He had a long-term urethral catheter because of urinary retention following a
      previous stroke. He was treated conservatively with antibiotics before a surgical
      opinion was sought. Exploratory laparotomy confirmed the diagnosis of spontaneous
      bladder rupture. After repair of the defect, he eventually made a full recovery.
      CONCLUSION: In this unusual case report, we describe an example of a serious
      event in which delays in diagnosis may lead to increased morbidity and mortality.
      To date, no unifying theory explaining why rupture occurs has been postulated. We
      conducted a thorough literature search to examine the etiological factors in
      other published cases. These etiological factors either increase intra-vesical
      pressure or decrease the strength of the bladder wall. We hope that by increasing
      awareness of these etiological factors, spontaneous bladder rupture may be
      diagnosed earlier and appropriate therapy started.

PMID- 21714889
TI  - Malignant neuroleptic syndrome following deep brain stimulation surgery: a case
      report.
AB  - BACKGROUND: The neuroleptic malignant syndrome is an uncommon but dangerous
      complication characterized by hyperthermia, autonomic dysfunction, altered mental
      state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It
      is most often caused by an adverse reaction to anti-psychotic drugs or abrupt
      discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our
      knowledge, it has never been reported following the common practice of
      discontinuation of anti-parkinsonian drugs during the pre-operative preparation
      for deep brain stimulation surgery for Parkinson's disease. CASE PRESENTATION: We
      present the first case of neuroleptic malignant syndrome associated with
      discontinuation of anti-parkinsonian medication prior to deep brain stimulation
      surgery in a 54-year-old Caucasian man. CONCLUSION: The characteristic
      neuroleptic malignant syndrome symptoms can be attributed to other, more common
      causes associated with deep brain stimulation treatment for Parkinson's disease,
      thus requiring a high index of clinical suspicion to timely establish the correct
      diagnosis. As more centers become eligible to perform deep brain stimulation,
      neurologists and neurosurgeons alike should be aware of this potentially fatal
      complication. Timely activation of the deep brain stimulation system may be
      important in accelerating the patient's recovery.

PMID- 21714890
TI  - Effect of fruit and vegetable concentrates on endothelial function in metabolic
      syndrome: a randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Dehydrated fruit and vegetable concentrates provide an
      accessible form of phytonutrient supplementation that may offer cardioprotective
      effects. This study assessed the effects of two blends of encapsulated juice
      powder concentrates (with and without added berry powders) on endothelial
      function in persons with metabolic syndrome, a risk factor for type 2 diabetes
      and cardiovascular disease. METHODS: Randomized, double blind, placebo controlled
      crossover clinical trial with three treatment arms. 64 adults with metabolic
      syndrome were enrolled and received 8-week sequences of each blend of the
      concentrates and placebo. The primary outcome measure was change in endothelial
      function (assessed as flow-mediated dilatation of the brachial artery) 2 hr after
      consuming a 75 g glucose load, after 8-weeks of daily consumption (sustained) or
      2 hr after consumption of a single dose (acute). Secondary outcome measures
      included plasma glucose, serum insulin, serum lipids, and body weight. RESULTS:
      No significant between-group differences in endothelial function with daily
      treatment for 8 weeks were seen. No other significant treatment effects were
      discerned in glucose, insulin, lipids, and weight. CONCLUSION: Encapsulated fruit
      and vegetable juice powder concentrates did not alter insulin or glucose measures
      in this sample of adults with metabolic syndrome. TRIAL REGISTRATION:
      clinicaltrials.gov NCT01224743.

PMID- 21714891
TI  - Lateral trunk motion and knee pain in osteoarthritis of the knee: a cross
      sectional study.
AB  - BACKGROUND: Patients with osteoarthritis of the knee may change their gait in an
      attempt to reduce loading of the affected knee, thereby reducing pain. Especially
      changes in lateral trunk motion may be potentially effective, since these will
      affect the position of the centre of mass relative to the knee, enabling
      minimization of the load on the knee and thereby knee pain. The aim of the study
      was to test the hypothesis that a higher level of knee pain is associated with
      higher lateral trunk motion in patients with knee OA. METHODS: Fifty-two patients
      with OA of the knee were tested. Lateral trunk motion was measured during the
      stance phase of walking with an optoelectronic motion analysis system and a force
      plate. Knee pain was measured with the VAS and the WOMAC pain questionnaire.
      Regression analyses were performed to assess the relationship between lateral
      trunk motion and knee pain. RESULTS: It was shown that in bivariate analyses knee
      pain was not associated with lateral trunk motion. In regression analyses, pain
      was associated with more lateral trunk motion. In addition, more lateral trunk
      motion was associated with younger age, being female, higher self-reported knee
      stiffness and higher maximum walking speed. CONCLUSION: Pain is associated with
      lateral trunk motion. This association is weak and is influenced by age, gender,
      self-reported stiffness and maximum walking speed.

PMID- 21714892
TI  - Words matter: a qualitative investigation of which weight status terms are
      acceptable and motivate weight loss when used by health professionals.
AB  - BACKGROUND: Health professionals have an important role to play in the management
      of obesity, but may be unsure how to raise weight issues with patients. The
      societal stigma associated with excess weight means that weight status terms may
      be misunderstood, cause offence and risk upsetting patient-professional
      relationships. This study investigated the views of people who were overweight or
      obese on the acceptability of weight status terms and their potential to motivate
      weight loss when used by health professionals. METHODS: A qualitative study
      comprising 34 semi-structured interviews with men and women in their mid-to-late
      30s and 50s who were overweight or obese and had recently been informed of their
      weight status. Thematic framework analysis was conducted to allow the systematic
      comparison of views by age, gender and apparent motivation to lose weight.
      RESULTS: Although many people favoured 'Overweight' to describe their weight
      status, there were doubts about its effectiveness to motivate weight loss. Terms
      including 'BMI' ('Body Mass Index') or referring to the unhealthy nature of their
      weight were generally considered acceptable and motivational, although a number
      of men questioned the validity of BMI as an indicator of excess weight.
      Participants, particularly women, felt that health professionals should avoid
      using 'Fat'. Whilst response to 'Obese' was largely negative, people recognised
      that it could be appropriate in a health consultation. Some younger people,
      particularly those who appeared motivated to lose weight, felt 'Obese' could
      encourage weight loss, but it was also clear the term could provoke negative
      emotions if used insensitively. CONCLUSIONS: Although most people who are
      overweight or obese accept that it is appropriate for health professionals to
      discuss weight issues with patients, there is great variation in response to the
      terms commonly used to describe excess weight. There is no one-size-fits-all
      approach to discussing weight status: some men and younger people may appreciate
      a direct approach, whilst others need to be treated more sensitively. It is
      therefore important that health professionals use their knowledge and
      understanding to select the terms that are most likely to be acceptable, but at
      the same time have most potential to motivate each individual patient.

PMID- 21714893
TI  - Contributions and challenges of cross-national comparative research in migration,
      ethnicity and health: insights from a preliminary study of maternal health in
      Germany, Canada and the UK.
AB  - BACKGROUND: Public health researchers are increasingly encouraged to establish
      international collaborations and to undertake cross-national comparative studies.
      To-date relatively few such studies have addressed migration, ethnicity and
      health, but their number is growing. While it is clear that divergent approaches
      to such comparative research are emerging, public health researchers have not so
      far given considered attention to the opportunities and challenges presented by
      such work. This paper contributes to this debate by drawing on the experience of
      a recent study focused on maternal health in Canada, Germany and the UK.
      DISCUSSION: The paper highlights various ways in which cross-national comparative
      research can potentially enhance the rigour and utility of research into
      migration, ethnicity and health, including by: forcing researchers to engage in
      both ideological and methodological critical reflexivity; raising awareness of
      the socially and historically embedded nature of concepts, methods and generated
      'knowledge'; increasing appreciation of the need to situate analyses of health
      within the wider socio-political setting; helping researchers (and research
      users) to see familiar issues from new perspectives and find innovative
      solutions; encouraging researchers to move beyond fixed 'groups' and 'categories'
      to look at processes of identification, inclusion and exclusion; promoting a
      multi-level analysis of local, national and global influences on migrant/minority
      health; and enabling conceptual and methodological development through the
      exchange of ideas and experience between diverse research teams. At the same
      time, the paper alerts researchers to potential downsides, including: significant
      challenges to developing conceptual frameworks that are meaningful across
      contexts; a tendency to reify concepts and essentialise migrant/minority 'groups'
      in an effort to harmonize across countries; a danger that analyses are
      superficial, being restricted to independent country descriptions rather than
      generating integrated insights; difficulties of balancing the need for meaningful
      findings at country level and more holistic products; and increased logistical
      complexity and costs. SUMMARY: In view of these pros and cons, the paper
      encourages researchers to reflect more on the rationale for, feasibility and
      likely contribution of proposed cross-national comparative research that engages
      with migration, ethnicity and health and suggests some principles that could
      support such reflection.

PMID- 21714894
TI  - The coupling of pathways and processes through shared components.
AB  - BACKGROUND: The coupling of pathways and processes through shared components is
      being increasingly recognised as a common theme which occurs in many cell
      signalling contexts, in which it plays highly non-trivial roles. RESULTS: In this
      paper we develop a basic modelling and systems framework in a general setting for
      understanding the coupling of processes and pathways through shared components.
      Our modelling framework starts with the interaction of two components with a
      common third component and includes production and degradation of all these
      components. We analyze the signal processing in our model to elucidate different
      aspects of the coupling. We show how different kinds of responses, including
      "ultrasensitive" and adaptive responses, may occur in this setting. We then build
      on the basic model structure and examine the effects of additional control
      regulation, switch-like signal processing, and spatial signalling. In the
      process, we identify a way in which allosteric regulation may contribute to
      signalling specificity, and how competitive effects may allow an enzyme to
      robustly coordinate and time the activation of parallel pathways. CONCLUSIONS: We
      have developed and analyzed a common systems platform for examining the effects
      of coupling of processes through shared components. This can be the basis for
      subsequent expansion and understanding the many biologically observed variations
      on this common theme.

PMID- 21714895
TI  - Care seeking and attitudes towards treatment compliance by newly enrolled
      tuberculosis patients in the district treatment programme in rural western Kenya:
      a qualitative study.
AB  - BACKGROUND: The two issues mostly affecting the success of tuberculosis (TB)
      control programmes are delay in presentation and non-adherence to treatment. It
      is important to understand the factors that contribute to these issues,
      particularly in resource limited settings, where rates of tuberculosis are high.
      The objective of this study is to assess health-seeking behaviour and health care
      experiences among persons with pulmonary tuberculosis, and identify the reasons
      patients might not complete their treatment. METHODS: We performed qualitative
      one-on-one in-depth interviews with pulmonary tuberculosis patients in nine
      health facilities in rural western Kenya. Thirty-one patients, 18 women and 13
      men, participated in the study. All reside in an area of western Kenya with a
      Health and Demographic Surveillance System (HDSS). They had attended treatment
      for up to 4 weeks on scheduled TB clinic days in September and October 2005.The
      nine sites all provide diagnostic and treatment services. Eight of the facilities
      were public (3 hospitals and 5 health centres) and one was a mission health
      centre. RESULTS: Most patients initially self-treated with herbal remedies or
      drugs purchased from kiosks or pharmacies before seeking professional care. The
      reported time from initial symptoms to TB diagnosis ranged from 3 weeks to 9
      years. Misinterpretation of early symptoms and financial constraints were the
      most common reasons reported for the delay.We also explored potential reasons
      that patients might discontinue their treatment before completing it. Reasons
      included being unaware of the duration of TB treatment, stopping treatment once
      symptoms subsided, and lack of family support. CONCLUSIONS: This qualitative
      study highlighted important challenges to TB control in rural western Kenya, and
      provided useful information that was further validated in a quantitative study in
      the same area.

PMID- 21714896
TI  - DOSim: an R package for similarity between diseases based on Disease Ontology.
AB  - BACKGROUND: The construction of the Disease Ontology (DO) has helped promote the
      investigation of diseases and disease risk factors. DO enables researchers to
      analyse disease similarity by adopting semantic similarity measures, and has
      expanded our understanding of the relationships between different diseases and to
      classify them. Simultaneously, similarities between genes can also be analysed by
      their associations with similar diseases. As a result, disease heterogeneity is
      better understood and insights into the molecular pathogenesis of similar
      diseases have been gained. However, bioinformatics tools that provide easy and
      straight forward ways to use DO to study disease and gene similarity
      simultaneously are required. RESULTS: We have developed an R-based software
      package (DOSim) to compute the similarity between diseases and to measure the
      similarity between human genes in terms of diseases. DOSim incorporates a DO
      based enrichment analysis function that can be used to explore the disease
      feature of an independent gene set. A multilayered enrichment analysis (GO and
      KEGG annotation) annotation function that helps users explore the biological
      meaning implied in a newly detected gene module is also part of the DOSim
      package. We used the disease similarity application to demonstrate the
      relationship between 128 different DO cancer terms. The hierarchical clustering
      of these 128 different cancers showed modular characteristics. In another case
      study, we used the gene similarity application on 361 obesity-related genes. The
      results revealed the complex pathogenesis of obesity. In addition, the gene
      module detection and gene module multilayered annotation functions in DOSim when
      applied on these 361 obesity-related genes helped extend our understanding of the
      complex pathogenesis of obesity risk phenotypes and the heterogeneity of obesity
      related diseases. CONCLUSIONS: DOSim can be used to detect disease-driven gene
      modules, and to annotate the modules for functions and pathways. The DOSim
      package can also be used to visualise DO structure. DOSim can reflect the modular
      characteristic of disease related genes and promote our understanding of the
      complex pathogenesis of diseases. DOSim is available on the Comprehensive R
      Archive Network (CRAN) or http://bioinfo.hrbmu.edu.cn/dosim.

PMID- 21714897
TI  - The ratio of CRP to prealbumin levels predict mortality in patients with hospital
      acquired acute kidney injury.
AB  - BACKGROUND: Animal and human studies suggest that inflammation and malnutrition
      are common in acute kidney injury (AKI) patients. However, only a few studies
      reported CRP, a marker of inflammation, albumin, prealbumin and cholesterol,
      markers of nutritional status were associated with the prognosis of AKI patients.
      No study examined whether the combination of inflammatory and nutritional markers
      could predict the mortality of AKI patients. METHODS: 155 patients with hospital
      acquired AKI were recruited to this prospective cohort study according to RIFLE
      (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. C-reactive protein
      (CRP), and the nutritional markers (albumin, prealbumin and cholesterol) measured
      at nephrology consultation were analyzed in relation to all cause mortality of
      these patients. In addition, CRP and prealbumin were also measured in healthy
      controls (n = 45), maintenance hemodialysis (n = 70) and peritoneal dialysis
      patients (n = 50) and then compared with AKI patients. RESULTS: Compared with
      healthy controls and end-stage renal disease patients on maintenance hemodialysis
      or peritoneal dialysis, patients with AKI had significantly higher levels of
      CRP/prealbumin (p < 0.001). Higher level of serum CRP and lower levels of
      albumin, prealbumin and cholesterol were found to be significant in the patients
      with AKI who died within 28 days than those who survived >28 days. Similarly, the
      combined factors including the ratio of CRP to albumin (CRP/albumin),
      CRP/prealbumin and CRP/cholesterol were also significantly higher in the former
      group (p < 0.001 for all). Multivariate analysis (Cox regression) revealed that
      CRP/prealbumin was independently associated with mortality after adjustment for
      age, gender, sepsis and sequential organ failure assessment (SOFA, p = 0.027)
      while the others (CRP, albumin, prealbumin, cholesterol, CRP/albumin and
      CRP/cholesterol) became non-significantly associated. The hazard ratio was 1.00
      (reference), 1.85, 2.25 and 3.89 for CRP/prealbumin increasing according to
      quartiles (p = 0.01 for the trend). CONCLUSIONS: Inflammation and malnutrition
      were common in patients with AKI. Higher level of the ratio of CRP to prealbumin
      was associated with mortality of AKI patients independent of the severity of
      illness and it may be a valuable addition to SOFA score to independent of the
      severity of illness and it may be a valuable addition to SOFA score to predict
      the prognosis of AKI patients.

PMID- 21714898
TI  - Development of a highly sensitive real-time one step RT-PCR combined
      complementary locked primer technology and conjugated minor groove binder probe.
AB  - BACKGROUND: Enterovirus (EV) infections are commonly associated with encephalitis
      and meningitis. Detection of enteroviral RNA in clinical specimens has been
      demonstrated to improve the management of patients, by ruling out other causes of
      disease. METHOD: To develop a sensitive and reliable assay for routine laboratory
      diagnosis, we developed a real-time one step reverse transcription polymerase
      chain reaction (RT-PCR) assay with minor groove binder probes and primers
      modified with complementary locked primer technology (TMC-PCR). We checked the
      sensitivity of the developed assay by comparing it to a previously published
      TaqMan probe real-time one-step RT-PCR (TTN-PCR) procedure using enteroviral
      isolates, Enterovirus Proficiency panels from Quality Control on Molecular
      Diagnostics (QCMD-2007), and clinical specimens from patients with suspected EV
      infections. RESULTS: One hundred clinical specimens from 158 suspected viral
      meningitis cases were determined to be positive by the TMC-PCR assay (63.29%),
      whereas only 60 were found to be positive by the TTN-PCR assay (37.97%). The
      positive and negative agreements between the TMC-PCR and TTN-PCR assays were 100%
      and 59.2%, respectively. CONCLUSION: This data suggest that the TMC-PCR assay may
      be suitable for routine diagnostic screening from patient suspected EV infection.

PMID- 21714899
TI  - The complete genome sequence and genetic analysis of PhiCA82 a novel uncultured
      microphage from the turkey gastrointestinal system.
AB  - The genomic DNA sequence of a novel enteric uncultured microphage, PhiCA82 from a
      turkey gastrointestinal system was determined utilizing metagenomics techniques.
      The entire circular, single-stranded nucleotide sequence of the genome was 5,514
      nucleotides. The PhiCA82 genome is quite different from other microviruses as
      indicated by comparisons of nucleotide similarity, predicted protein similarity,
      and functional classifications. Only three genes showed significant similarity to
      microviral proteins as determined by local alignments using BLAST analysis. ORF1
      encoded a predicted phage F capsid protein that was phylogenetically most similar
      to the Microviridae PhiMH2K member's major coat protein. The PhiCA82 genome also
      encoded a predicted minor capsid protein (ORF2) and putative replication
      initiation protein (ORF3) most similar to the microviral bacteriophage SpV4. The
      distant evolutionary relationship of PhiCA82 suggests that the divergence of this
      novel turkey microvirus from other microviruses may reflect unique evolutionary
      pressures encountered within the turkey gastrointestinal system.

PMID- 21714900
TI  - Convergence of developmental mutants into a single tomato model system: 'Micro
      Tom' as an effective toolkit for plant development research.
AB  - BACKGROUND: The tomato (Solanum lycopersicum L.) plant is both an economically
      important food crop and an ideal dicot model to investigate various physiological
      phenomena not possible in Arabidopsis thaliana. Due to the great diversity of
      tomato cultivars used by the research community, it is often difficult to
      reliably compare phenotypes. The lack of tomato developmental mutants in a single
      genetic background prevents the stacking of mutations to facilitate analysis of
      double and multiple mutants, often required for elucidating developmental
      pathways. RESULTS: We took advantage of the small size and rapid life cycle of
      the tomato cultivar Micro-Tom (MT) to create near-isogenic lines (NILs) by
      introgressing a suite of hormonal and photomorphogenetic mutations (altered
      sensitivity or endogenous levels of auxin, ethylene, abscisic acid, gibberellin,
      brassinosteroid, and light response) into this genetic background. To demonstrate
      the usefulness of this collection, we compared developmental traits between the
      produced NILs. All expected mutant phenotypes were expressed in the NILs. We also
      created NILs harboring the wild type alleles for dwarf, self-pruning and uniform
      fruit, which are mutations characteristic of MT. This amplified both the
      applications of the mutant collection presented here and of MT as a genetic model
      system. CONCLUSIONS: The community resource presented here is a useful toolkit
      for plant research, particularly for future studies in plant development, which
      will require the simultaneous observation of the effect of various hormones,
      signaling pathways and crosstalk.

PMID- 21714901
TI  - Forensic child and Adolescent Psychiatry and mental health in Europe.

PMID- 21714902
TI  - Lack of macrophage migration inhibitory factor in mice does not affect hallmarks
      of the inflammatory/immune response during the first week after stroke.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) has been proposed to
      play a detrimental role in stroke. We recently showed that MIF promotes neuronal
      death and aggravates neurological deficits during the first week after
      experimental stroke, in mice. Since MIF regulates tissue inflammation, we studied
      the putative role of MIF in post-stroke inflammation. METHODS: We subjected
      C57BL/6 mice, Mif-/- (MIF-KO) or Mif+/+ (WT), to a transient occlusion of the
      right middle cerebral artery (tMCAo) or sham-surgery. We studied MIF expression,
      GFAP expression and the number of CD74-positive cells in the ischemic brain
      hemisphere 7 days after tMCAo using primarily immunohistochemistry. We determined
      IFN-gamma, IL-2, IL-4, IL-5, IL-10, IL-12, KC/CXCL-1 and TNF-alpha protein levels
      in the brain (48 h after surgery) and serum (48 h and 7 days after surgery) by a
      multiplex immunoassay. RESULTS: We observed that MIF accumulates in neurons and
      astrocytes of the peri-infarct region, as well as in microglia/macrophages of the
      infarct core up to 7 days after stroke. Among the inflammatory mediators
      analyzed, we found a significant increase in cerebral IL-12 and KC levels after
      tMCAo, in comparison to sham-surgery. Importantly, the deletion of Mif did not
      significantly affect the levels of the cytokines evaluated, in the brain or
      serum. Moreover, the spleen weight 48 h and 7 days subsequent to tMCAo was
      similar in WT and MIF-KO mice. Finally, the extent of GFAP immunoreactivity and
      the number of MIF receptor (CD74)-positive cells within the ischemic brain
      hemisphere did not differ significantly between WT and MIF-KO mice subjected to
      tMCAo. CONCLUSIONS: We conclude that MIF does not affect major components of the
      inflammatory/immune response during the first week after experimental stroke.
      Based on present and previous evidence, we propose that the deleterious MIF
      mediated effects in stroke depend primarily on an intraneuronal and/or
      interneuronal action.

PMID- 21714903
TI  - Measuring and modelling occupancy time in NHS continuing healthcare.
AB  - BACKGROUND: Due to increasing demand and financial constraints, NHS continuing
      healthcare systems seek to find better ways of forecasting demand and budgeting
      for care. This paper investigates two areas of concern, namely, how long existing
      patients stay in service and the number of patients that are likely to be still
      in care after a period of time. METHODS: An anonymised dataset containing
      information for all funded admissions to placement and home care in the NHS
      continuing healthcare system was provided by 26 (out of 31) London primary care
      trusts. The data related to 11289 patients staying in placement and home care
      between 1 April 2005 and 31 May 2008 were first analysed. Using a methodology
      based on length of stay (LoS) modelling, we captured the distribution of LoS of
      patients to estimate the probability of a patient staying in care over a period
      of time. Using the estimated probabilities we forecasted the number of patients
      that are likely to be still in care after a period of time (e.g. monthly).
      RESULTS: We noticed that within the NHS continuing healthcare system there are
      three main categories of patients. Some patients are discharged after a short
      stay (few days), some others staying for few months and the third category of
      patients staying for a long period of time (years). Some variations in
      proportions of discharge and transition between types of care as well as between
      care groups (e.g. palliative, functional mental health) were observed. A close
      agreement of the observed and the expected numbers of patients suggests a good
      prediction model. CONCLUSIONS: The model was tested for care groups within the
      NHS continuing healthcare system in London to support Primary Care Trusts in
      budget planning and improve their responsiveness to meet the increasing demand
      under limited availability of resources. Its applicability can be extended to
      other types of care, such as hospital care and re-ablement. Further work will be
      geared towards updating the dataset and refining the results.

PMID- 21714904
TI  - Parenteral lidocaine for treatment of intractable renal colic: a case series.
AB  - INTRODUCTION: We report a case series of successful treatment of intractable
      renal colic using parenteral lidocaine. CASE PRESENTATION: Because of
      inconsistent responses to standard treatment with opioids and non-steroidal anti
      inflammatory drugs in patients with renal colic pain, we decided to begin a trial
      of a single intravenous dose of lidocaine (approximately 1.5 mg/kg) slowly in
      eight patients with intractable renal colic who were referred to our emergency
      medicine department. The patients were six men and two women with a mean age at
      diagnosis of 34.62 years (age range, 28 to 42 years). The patients were of
      Iranian ethnic origin. The patients' degree of pain, based on Visual Analog Scale
      score upon entering our emergency medicine department, was recorded 10, 20, and
      30 minutes after lidocaine injection. The patients' degree of pain decreased from
      a mean Visual Analog Scale score (+/-SD) of 8.87 +/- 0.99 (95% confidence
      interval (95% CI) 8.04 to 9.70) to a mean Visual Analog Scale score (+/-SD) of 1
      +/- 2.82 (95% CI -1.36 to 3.36) before and 30 minutes after lidocaine treatment,
      respectively. Two of eight patients experienced transient mild dizziness, and
      three of eight patients experienced minimal slurring of speech. No patient
      experienced serious adverse events. CONCLUSION: Parenteral lidocaine treatment
      can reduce pain dramatically or subtly.

PMID- 21714905
TI  - Psychopathology, trauma and delinquency: subtypes of aggression and their
      relevance for understanding young offenders.
AB  - OBJECTIVE: To examine the implications of an ontology of aggressive behavior
      which divides aggression into reactive, affective, defensive, impulsive (RADI) or
      "emotionally hot"; and planned, instrumental, predatory (PIP) or "emotionally
      cold." Recent epidemiological, criminological, clinical and neuroscience studies
      converge to support a connection between emotional and trauma related
      psychopathology and disturbances in the emotions, self-regulation and aggressive
      behavior which has important implications for diagnosis and treatment, especially
      for delinquent populations. METHOD: Selective review of preclinical and clinical
      studies in normal, clinical and delinquent populations. RESULTS: In delinquent
      populations we observe an increase in psychopathology, and especially trauma
      related psychopathology which impacts emotions and self-regulation in a manner
      that hotly emotionally charged acts of aggression become more likely. The
      identification of these disturbances can be supported by findings in cognitive
      neuroscience. These hot aggressive acts can be delineated from planned or
      emotionally cold aggression. CONCLUSION: Our findings support a typology of
      diagnostic labels for disruptive behaviors, such as conduct disorder and
      oppositional defiant disorder, as it appears that these acts of hot emotional
      aggression are a legitimate target for psychopharmacological and other trauma
      specific interventions. The identification of this subtype of disruptive behavior
      disorders leads to more specific clinical interventions which in turn promise to
      improve hitherto unimpressive treatment outcomes of delinquents and patients with
      disruptive behavior.

PMID- 21714906
TI  - Correlates of self-reported offending in children with a first police contact
      from distinct socio-demographic and ethnic groups.
AB  - BACKGROUND: This study aims to identify risk factors for level of offending among
      childhood offenders from different socio-economic status (SES) neighborhoods and
      ethnic origins. METHOD: Three groups of childhood first time police arrestees
      were studied using standardized instruments for individual and parental
      characteristics: native Dutch offenders from moderate to high SES neighborhoods,
      native Dutch offenders from low SES neighborhoods, and offenders of non-Western
      origin from low SES neighborhoods. RESULTS: All subgroups showed high rates of
      externalizing disorders (27.2% to 41.8%) and familial difficulties (25.7% to
      50.5%). Few differences between neighborhoods were found in the prevalence and
      impact of risk factors. However, the impact of some family risk factors on
      offending seemed stronger in the low SES groups. Regarding ethnical differences,
      family risk factors were more prevalent among non-Western childhood offenders.
      However, the association of these factors with level of offending seemed lower in
      the non-Western low SES group, while the association of some individual risk
      factors were stronger in the non-Western low SES group. Turning to the
      independent correlation of risk factors within each of the groups, in the Dutch
      moderate to high SES group, 23.1% of the variance in level of offending was
      explained by ADHD and behavioral problems; in the Dutch low SES group, 29.0% of
      the variance was explained by behavioral problems and proactive aggression; and
      in the non-Western low SES group, 41.2% of the variance was explained by
      substance use, sensation seeking, behavioral peer problems, and parental mental
      health problems. CONCLUSIONS: Thereby, the study indicates few neighborhood
      differences in the impact of individual and parental risk factors on offending,
      while individual and parental risk factors may differ between ethnic groups.

PMID- 21714907
TI  - Ethnic differences in the mother-son relationship of incarcerated and non
      incarcerated male adolescents in the Netherlands.
AB  - BACKGROUND: In the Netherlands, youths of Moroccan origin account for a
      disproportionately large percentage of the population in juvenile justice
      institutions. Previous research showed that Moroccan adolescents in pre-trial
      arrest are characterized by less serious offending behavior (i.e., primarily
      property-based) and lower levels of mental health problems than native Dutch
      adolescents in pre-trial arrest. To date, little is known about the parent-child
      relationship of these adolescents. This study examines the mother-son
      relationships of Moroccan and native Dutch delinquent adolescents and their
      association with adolescent delinquency. METHODS: In the present study,
      differences in the mother-son relationship characteristics between families of
      incarcerated (N = 129) and non-incarcerated (N = 324) adolescents were examined,
      and it was analyzed if these differences between incarcerated and non
      incarcerated adolescents were the same for Moroccans and native Dutch. Data
      collection for the incarcerated sample took place from 2006 to 2008. Comparison
      data were used of interviews conducted with mothers originating from former
      larger studies in the general Dutch population. Latent Class Analysis was
      performed in order to identify types of mother-son relationship. Logistic
      regression analyses were used to identify the relationships between mother-son
      relationship types, incarceration and ethnicity. RESULTS: A three class model of
      mother-son relationship types was found: a low-conflict mother-son relationship
      type, a high-conflict mother-son relationship type, and a neglectful mother-son
      relationship type. Compared to the native Dutch adolescents, Moroccans (both in
      the incarcerated and non-incarcerated population) more often showed a neglectful
      mother-son relationship type. For Moroccans, no differences in mother-son
      relationship types were found between the incarcerated and non-incarcerated
      adolescents, whereas considerable differences occurred between the native Dutch
      incarcerated and non-incarcerated adolescents. CONCLUSIONS: Our findings indicate
      that mother-son relationship types of incarcerated Moroccan adolescents and non
      incarcerated Moroccan adolescents are rather comparable. These findings are in
      line with previous studies which revealed the less problematic profile of
      Moroccan adolescents in pre-trial arrest in the Netherlands compared to native
      Dutch adolescents in pre-trial arrest.

PMID- 21714908
TI  - Large-scale analysis of chromosomal aberrations in cancer karyotypes reveals two
      distinct paths to aneuploidy.
AB  - BACKGROUND: Chromosomal aneuploidy, that is to say the gain or loss of
      chromosomes, is the most common abnormality in cancer. While certain aberrations,
      most commonly translocations, are known to be strongly associated with specific
      cancers and contribute to their formation, most aberrations appear to be non
      specific and arbitrary, and do not have a clear effect. The understanding of
      chromosomal aneuploidy and its role in tumorigenesis is a fundamental open
      problem in cancer biology. RESULTS: We report on a systematic study of the
      characteristics of chromosomal aberrations in cancers, using over 15,000
      karyotypes and 62 cancer classes in the Mitelman Database. Remarkably, we
      discovered a very high co-occurrence rate of chromosome gains with other
      chromosome gains, and of losses with losses. Gains and losses rarely show
      significant co-occurrence. This finding was consistent across cancer classes and
      was confirmed on an independent comparative genomic hybridization dataset of
      cancer samples. The results of our analysis are available for further
      investigation via an accompanying website. CONCLUSIONS: The broad generality and
      the intricate characteristics of the dichotomy of aneuploidy, ranging across
      numerous tumor classes, are revealed here rigorously for the first time using
      statistical analyses of large-scale datasets. Our finding suggests that aneuploid
      cancer cells may use extra chromosome gain or loss events to restore a balance in
      their altered protein ratios, needed for maintaining their cellular fitness.

PMID- 21714909
TI  - Cortical gene transcription response patterns to water maze training in aged
      mice.
AB  - BACKGROUND: The hippocampus mediates the acquisition of spatial memory, but the
      memory trace is eventually transferred to the cortex. We have investigated
      transcriptional activation of pathways related to cognitive function in the
      cortex of the aged mouse by analyzing gene expression following water maze
      training. RESULTS: We identified genes that were differentially responsive in
      aged mice with accurate spatial performance during probe trials or repeated
      swimming sessions, relative to home cage conditions. Effective learners exhibited
      significantly greater activation of several pathways, such as the mitogen
      activated protein kinase and insulin receptor signaling pathways, relative to
      swimmers. The genes encoding activity-related cytoskeletal protein (Arc) and
      brain-derived neurotrophic factor (BDNF) were upregulated in proficient learners,
      relative to swimmers and home cage controls, while the gene encoding Rho GTPase
      activating protein 32 (GRIT) was downregulated. We explored the regulation of
      Arc, BDNF, and GRIT expression in greater morphological detail using in situ
      hybridization. Recall during probe trials enhanced Arc expression across multiple
      cortical regions involved in the cognitive component of water maze learning,
      while BDNF expression was more homogeneously upregulated across cortical regions
      involved in the associational and sensorimotor aspects of water maze training. In
      contrast, levels of GRIT expression were uniformly reduced across all cortical
      regions examined. CONCLUSIONS: These results suggest that cortical gene
      transcription is responsive to learning in aged mice that exhibit behavioral
      proficiency, and support a distributed hypothesis of memory storage across
      multiple cortical compartments.

PMID- 21714910
TI  - Assessing the psychometric properties and the perceived usefulness of the
      BasisRaadsOnderzoek (BARO) as a first-line screening instrument for juvenile
      offenders.
AB  - BACKGROUND: The aim of this study is to investigate the psychometric properties
      and the perceived usefulness of the BARO (Dutch: BAsisRaadsOnderzoek; Protection
      Board Preliminary Examination of Juvenile Suspects). The BARO is a first-line
      screening instrument for the identification of psychiatric disorders, adverse
      environmental factors, and levels of (dys)function in adolescent offenders (age
      12 to 18), to be used by social workers of the Child Protection Board (CPB)
      following a police arrest. METHOD: CPB workers administered the BARO to 295
      juvenile offenders (91% boys, 9% girls). A subgroup of 66 offenders (89% boys,
      11% girls) underwent an elaborate diagnostic assessment by forensic psychologists
      and psychiatrists. Using these assessments the most relevant psychometric
      properties of the BARO were studied. The perceived usefulness was studied using
      questionnaires to be filled in by the CPB social workers. RESULTS: The internal
      consistency of the instrument was sufficient to good, the concurrent validity of
      the CPB social workers applying the BARO and the forensic experts carrying out
      the comprehensive diagnostic assessment was strong, the discriminatory value of
      the instrument was moderate to strong, and the perceived usefulness of the
      instrument was evaluated as good to very good by the majority of the CPB workers.
      DISCUSSION: The BARO has sufficient to good psychometric properties including
      moderate to strong discriminatory value and is considered a good screening
      instrument by the CPB social workers. In conclusion, the BARO seems to be a very
      promising first-line screening instrument to identify psychiatric and
      psychosocial problems in young offenders.

PMID- 21714911
TI  - Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene.
AB  - BACKGROUND: Benzo[a]pyrene (BaP) is a widespread environmental genotoxic
      carcinogen that damages DNA by forming adducts. This damage along with activation
      of the aryl hydrocarbon receptor (AHR) induces complex transcriptional responses
      in cells. To investigate whether human cells are more susceptible to BaP in a
      particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells
      were exposed to BaP. Cell cycle progression was analysed by flow cytometry, DNA
      adduct formation was assessed by 32P-postlabeling analysis, microarrays of 44K
      human genome-wide oligos and RT-PCR were used to detect gene expression (mRNA)
      changes and Western blotting was performed to determine the expression of some
      proteins, including cytochrome P450 (CYP) 1A1 and CYP1B1, which are involved in
      BaP metabolism. RESULTS: Following BaP exposure, cells evaded G1 arrest and
      accumulated in S-phase. Higher levels of DNA damage occurred in S- and G2/M-
      compared with G0/G1-enriched cultures. Genes that were found to have altered
      expression included those involved in xenobiotic metabolism, apoptosis, cell
      cycle regulation and DNA repair. Gene ontology and pathway analysis showed the
      involvement of various signalling pathways in response to BaP exposure, such as
      the Catenin/Wnt pathway in G1, the ERK pathway in G1 and S, the Nrf2 pathway in S
      and G2/M and the Akt pathway in G2/M. An important finding was that higher levels
      of DNA damage in S- and G2/M-enriched cultures correlated with higher levels of
      CYP1A1 and CYP1B1 mRNA and proteins. Moreover, exposure of synchronised MCF-7
      cells to BaP-7,8-diol-9,10-epoxide (BPDE), the ultimate carcinogenic metabolite
      of BaP, did not result in significant changes in DNA adduct levels at different
      phases of the cell cycle. CONCLUSIONS: This study characterised the complex gene
      response to BaP in MCF-7 cells and revealed a strong correlation between the
      varying efficiency of BaP metabolism and DNA damage in different phases of the
      cell cycle. Our results suggest that growth kinetics within a target-cell
      population may be important determinants of susceptibility and response to a
      genotoxic agent.

PMID- 21714913
TI  - Examination of submental space as an alternative method of airway assessment
      (submental sign).
AB  - BACKGROUND: Difficult airway especially failed intubation has been associated
      with a high incidence of mortality and morbidity. Most of mortalities occur when
      an anaesthesiologist encounters an unanticipated difficult airway. FINDINGS: In
      1999, a 23 yr. old, 65 kg weight and 170 cm height female patient had been
      scheduled for arthroscopy. Despite totally normal airway assessment (thyromental
      distance, mouth opening, jaw and neck movement ...) I was astonished by
      encountering a grade IV Cormack - Lehane laryngoscopic view. Tracheal intubation
      was impossible and ventilation was very difficult.On attempt to attain a better
      laryngoscopic view, while manipulating submandibular region I encountered a bulky
      noncompliant submental space (Submental Sign). This event made me more alert
      regarding this finding. Thereafter I noted for this sign throughout the past
      years and I found it very helpful.These findings encouraged me to write this
      report, and suggest a routine examination of submental space in order to keep the
      safety of the patient at the heart of the care we provide. CONCLUSION: Evaluation
      of the submental space is suggested as an alternative predictor of difficult
      airway and routine examination of the submental space is of value in airway
      assessment.

PMID- 21714912
TI  - Complete genome sequence of the filamentous anoxygenic phototrophic bacterium
      Chloroflexus aurantiacus.
AB  - BACKGROUND: Chloroflexus aurantiacus is a thermophilic filamentous anoxygenic
      phototrophic (FAP) bacterium, and can grow phototrophically under anaerobic
      conditions or chemotrophically under aerobic and dark conditions. According to
      16S rRNA analysis, Chloroflexi species are the earliest branching bacteria
      capable of photosynthesis, and Cfl. aurantiacus has been long regarded as a key
      organism to resolve the obscurity of the origin and early evolution of
      photosynthesis. Cfl. aurantiacus contains a chimeric photosystem that comprises
      some characters of green sulfur bacteria and purple photosynthetic bacteria, and
      also has some unique electron transport proteins compared to other photosynthetic
      bacteria. METHODS: The complete genomic sequence of Cfl. aurantiacus has been
      determined, analyzed and compared to the genomes of other photosynthetic
      bacteria. RESULTS: Abundant genomic evidence suggests that there have been
      numerous gene adaptations/replacements in Cfl. aurantiacus to facilitate life
      under both anaerobic and aerobic conditions, including duplicate genes and gene
      clusters for the alternative complex III (ACIII), auracyanin and NADH:quinone
      oxidoreductase; and several aerobic/anaerobic enzyme pairs in central carbon
      metabolism and tetrapyrroles and nucleic acids biosynthesis. Overall, genomic
      information is consistent with a high tolerance for oxygen that has been reported
      in the growth of Cfl. aurantiacus. Genes for the chimeric photosystem,
      photosynthetic electron transport chain, the 3-hydroxypropionate autotrophic
      carbon fixation cycle, CO2-anaplerotic pathways, glyoxylate cycle, and sulfur
      reduction pathway are present. The central carbon metabolism and sulfur
      assimilation pathways in Cfl. aurantiacus are discussed. Some features of the
      Cfl. aurantiacus genome are compared with those of the Roseiflexus castenholzii
      genome. Roseiflexus castenholzii is a recently characterized FAP bacterium and
      phylogenetically closely related to Cfl. aurantiacus. According to previous
      reports and the genomic information, perspectives of Cfl. aurantiacus in the
      evolution of photosynthesis are also discussed. CONCLUSIONS: The genomic analyses
      presented in this report, along with previous physiological, ecological and
      biochemical studies, indicate that the anoxygenic phototroph Cfl. aurantiacus has
      many interesting and certain unique features in its metabolic pathways. The
      complete genome may also shed light on possible evolutionary connections of
      photosynthesis.

PMID- 21714914
TI  - Is RNA-dependent RNA polymerase essential for transposon control?
AB  - BACKGROUND: Eukaryotes use RNA interference and RNA-based epigenetic regulation
      to control transposon activity. In the standard pathways of RNA-based
      transcriptional and post-transcriptional silencing the protein complex RNA
      dependent RNA polymerase (RdRP) plays a crucial role. However, alternative
      pathways that bypass RdRP have recently been described. Hence two important
      questions are: is RdRP truly a necessary component for transposon control, and
      are the alternative RNA-based strategies also capable of controlling transposable
      elements? RESULTS: We have studied the interplay between host RNAi pathways and
      transposons using mathematical models. We show that the canonical RdRP-based
      model controls transposons tightly, mainly via the feedback of cytoplasmic small
      RNA amplification. Next, we consider two variants lacking RdRP and instead
      employing antisense transcription of transposons. We show that transposon
      activity is also controlled by the alternative pathways, although cytoplasmic
      small RNA amplification is absent. Instead, control occurs in the nucleus,
      through a feedback in the epigenetic regulation. CONCLUSIONS: Concluding, our
      models show that the control of transposon activity can be achieved by
      alternative pathways that lack RdRP and act through different feedback
      mechanisms. Thus, although RdRP activity is ubiquitous in eukaryotes, it need not
      be a general requirement for transposon control.

PMID- 21714915
TI  - Real-world comparison of two molecular methods for detection of respiratory
      viruses.
AB  - BACKGROUND: Molecular polymerase chain reaction (PCR) based assays are
      increasingly used to diagnose viral respiratory infections and conduct
      epidemiology studies. Molecular assays have generally been evaluated by comparing
      them to conventional direct fluorescent antibody (DFA) or viral culture
      techniques, with few published direct comparisons between molecular methods or
      between institutions. We sought to perform a real-world comparison of two
      molecular respiratory viral diagnostic methods between two experienced
      respiratory virus research laboratories. METHODS: We tested nasal and throat swab
      specimens obtained from 225 infants with respiratory illness for 11 common
      respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay
      [RMA]) and individual real-time RT-PCR (RT-rtPCR). RESULTS: Both assays detected
      viruses in more than 70% of specimens, but there was discordance. The RMA assay
      detected significantly more human metapneumovirus (HMPV) and respiratory
      syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We
      speculated that primer differences accounted for these discrepancies and
      redesigned the primers and probes for influenza A in the RMA assay, and for HMPV
      and RSV in the RT-rtPCR assay. The tests were then repeated and again compared.
      The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but
      the RMA assay remained similar in terms of influenza detection. CONCLUSIONS:
      Given the absence of a gold standard, clinical and research laboratories should
      regularly correlate the results of molecular assays with other PCR based assays,
      other laboratories, and with standard virologic methods to ensure consistency and
      accuracy.

PMID- 21714916
TI  - Radiolucent lines in low-contact-stress mobile-bearing total knee arthroplasty: a
      blinded and matched case control study.
AB  - BACKGROUND: Low-contact-stress (LCS) mobile-bearing total knee arthroplasty (TKA)
      (Johnson & Johnson, New Brunswick, NJ; previously: DePuy, Warsawa, USA) provides
      excellent functional results and wear rates in long-term follow-up analyses.
      Radiological analysis shows radiolucent lines (RLL) appearing immediately or two
      years after primary implantation, indicative of poor seat. Investigations proved
      RLL to be more frequent in uncemented TKA, resulting in a consensus to cement the
      tibial plateau, but their association with clinical findings and patients
      discomfort and knee pain is still unknown. METHODS: 553 patients with 566 low
      contact-stress (LCS) total knee prostheses were screened for continuous moderate
      knee pain. We compared tibial stress shielding classified by Ewald in patients
      suffering from pain with a matched, pain-free control group on blinded X-rays. We
      hypothesized a positive correlation between pain and radiolucency and higher
      frequency of such radiolucent lines in the most medial and most lateral zones of
      the tibial plateau. RESULTS: Twenty-eight patients suffered from knee pain in
      total. Radiolucencies were detected in 27 of these cases and in six out of 28
      matched controls without knee pain. We could demonstrate a significant
      correlation of knee pain and radiolucencies, which appeared significantly more
      frequently in the outermost zones of the tibial plateau. CONCLUSION: Our findings
      suggest that radiolucent lines, representing poor implant seat, about the tibial
      plateau are associated with knee pain in LCS patients. Radiolucencies are
      observed more often in noncemented LCS, and cementing the tibial plateau might
      improve implant seat and reduce both radiolucent lines and associated knee pain.

PMID- 21714917
TI  - Test performance of faecal occult blood testing for the detection of bowel cancer
      in people with chronic kidney disease (DETECT) protocol.
AB  - BACKGROUND: Cancer is a major cause of mortality and morbidity in patients with
      chronic kidney disease (CKD). In patients without kidney disease, screening is a
      major strategy for reducing the risk of cancer and improving the health outcomes
      for those who developed cancers by detecting treatable cancers at an early stage.
      Among those with CKD, the effectiveness, the efficacy and patients' preferences
      for cancer screening are unknown. METHODS/DESIGN: This work describes the
      protocol for the DETECT study examining the effectiveness, efficiency and
      patient's perspectives of colorectal cancer screening using immunochemical faecal
      occult blood testing (iFOBT) for people with CKD. The aims of the DETECT study
      are 1) to determine the test performance characteristics of iFOBT screening in
      individuals with CKD, 2) to estimate the incremental costs and health benefits of
      iFOBT screening in CKD compared to no screening and 3) to elicit patients'
      perspective for colorectal cancer screening in the CKD population. Three
      different study designs will be used to explore the uncertainties surrounding
      colorectal cancer screening in CKD. A diagnostic test accuracy study of iFOBT
      screening will be conducted across all stages of CKD in patients ages 35-70.
      Using individually collected direct healthcare costs and outcomes from the
      diagnostic test accuracy study, cost-utility and cost-effective analyses will be
      performed to estimate the costs and health benefits of iFOBT screening in CKD.
      Qualitative in-depth interviews will be undertaken in a subset of participants
      from the diagnostic test accuracy study to investigate the perspectives,
      experiences, attitudes and beliefs about colorectal cancer screening among
      individuals with CKD. DISCUSSION: The DETECT study will target the three major
      unknowns about early cancer detection in CKD. Findings from our study will
      provide accurate and definitive estimates of screening efficacy and efficiency
      for colorectal cancer, and will allow better service planning and budgeting for
      early cancer detection in this at-risk population.The DETECT study is also
      registered with the Australia New Zealand Clinical Trials Registry
      ACTRN12611000538943.

PMID- 21714918
TI  - Relationship between behavioural coping strategies and acceptance in patients
      with fibromyalgia syndrome: elucidating targets of interventions.
AB  - BACKGROUND: Previous research has found that acceptance of pain is more
      successful than cognitive coping variables for predicting adjustment to pain.
      This research has a limitation because measures of cognitive coping rely on
      observations and reports of thoughts or attempts to change thoughts rather than
      on overt behaviours. The purpose of the present study, therefore, is to compare
      the influence of acceptance measures and the influence of different behavioural
      coping strategies on the adjustment to chronic pain. METHODS: A sample of 167
      individuals diagnosed with fibromyalgia syndrome completed the Chronic Pain
      Coping Inventory (CPCI) and the Chronic Pain Acceptance Questionnaire (CPAQ).
      RESULTS: Correlational analyses indicated that the acceptance variables were more
      related to distress and functioning than were behavioural coping variables. The
      average magnitudes of the coefficients for activity engagement and pain
      willingness (both subscales of pain acceptance) across the measures of distress
      and functioning were r = 0.42 and 0.25, respectively, meanwhile the average
      magnitude of the correlation between coping and functioning was r = 0.17.
      Regression analyses examined the independent, relative contributions of coping
      and acceptance to adjustment indicators and demonstrated that acceptance
      accounted for more variance than did coping variables. The variance contributed
      by acceptance scores ranged from 4.0 to 40%. The variance contributed by the
      coping variables ranged from 0 to 9%. CONCLUSIONS: This study extends the
      findings of previous work in enhancing the adoption of acceptance-based
      interventions for maintaining accurate functioning in fibromyalgia patients.

PMID- 21714919
TI  - Multiplicity: an organizing principle for cancers and somatic mutations.
AB  - BACKGROUND: With the advent of whole-genome analysis for profiling tumor tissue,
      a pressing need has emerged for principled methods of organizing the large
      amounts of resulting genomic information. We propose the concept of multiplicity
      measures on cancer and gene networks to organize the information in a clinically
      meaningful manner. Multiplicity applied in this context extends Fearon and
      Vogelstein's multi-hit genetic model of colorectal carcinoma across multiple
      cancers. METHODS: Using the Catalogue of Somatic Mutations in Cancer (COSMIC), we
      construct networks of interacting cancers and genes. Multiplicity is calculated
      by evaluating the number of cancers and genes linked by the measurement of a
      somatic mutation. The Kamada-Kawai algorithm is used to find a two-dimensional
      minimum energy solution with multiplicity as an input similarity measure. Cancers
      and genes are positioned in two dimensions according to this similarity. A third
      dimension is added to the network by assigning a maximal multiplicity to each
      cancer or gene. Hierarchical clustering within this three-dimensional network is
      used to identify similar clusters in somatic mutation patterns across cancer
      types. RESULTS: The clustering of genes in a three-dimensional network reveals a
      similarity in acquired mutations across different cancer types. Surprisingly, the
      clusters separate known causal mutations. The multiplicity clustering technique
      identifies a set of causal genes with an area under the ROC curve of 0.84 versus
      0.57 when clustering on gene mutation rate alone. The cluster multiplicity value
      and number of causal genes are positively correlated via Spearman's Rank Order
      correlation (rs(8) = 0.894, Spearman's t = 17.48, p < 0.05). A clustering
      analysis of cancer types segregates different types of cancer. All blood tumors
      cluster together, and the cluster multiplicity values differ significantly
      (Kruskal-Wallis, H = 16.98, df = 2, p < 0.05). CONCLUSION: We demonstrate the
      principle of multiplicity for organizing somatic mutations and cancers in
      clinically relevant clusters. These clusters of cancers and mutations provide
      representations that identify segregations of cancer and genes driving cancer
      progression.

PMID- 21714920
TI  - Antibiotic resistance and adhesion properties of oral Enterococci associated to
      dental caries.
AB  - BACKGROUND: Enterococci are increasingly associated with opportunistic infections
      in Humans but the role of the oral cavity as a reservoir for this species is
      unclear. This study aimed to explore the carriage rate of Enterococci in the oral
      cavity of Tunisian children and their antimicrobial susceptibility to a broad
      range of antibiotics together with their adherence ability to abiotic and biotic
      surfaces. RESULTS: In this study, 17 E. faecalis (27.5%) and 4 E. faecium (6.5%)
      were detected. The identified strains showed resistance to commonly used
      antibiotics. Among the 17 isolated E. faecalis, 12 strains (71%) were slime
      producers and 5 strains were non-producers. Among the 4 E. faecium, 2 strains
      were slime producers. All the tested strains were able to adhere to at least one
      of the two tested cell lines. Our result showed that 11 E. faecalis and 2 E.
      faecium strains adhered strongly to Hep-2 as well as to A549 cells. CONCLUSIONS:
      Drugs resistance and strong biofilm production abilities together with a high
      phenotypic adhesion to host cells are important equipment in E. faecalis and E.
      faecium which lead to their oral cavity colonization and focal infections.

PMID- 21714921
TI  - Determinants of internal medicine residents' choice in the Canadian R4 fellowship
      match: a qualitative study.
AB  - BACKGROUND: There is currently a discrepancy between Internal Medicine residents'
      decisions in the Canadian subspecialty fellowship match (known as the R4 match)
      and societal need. Some studies have been published examining factors that
      influence career choices. However, these were either demographic factors or
      factors pre-determined by the authors' opinion as possibly being important to
      incorporate into a survey. METHODS: A qualitative study was undertaken to
      identify factors that determine the residents choice in the subspecialty (R4)
      fellowship match using focus group discussions involving third and fourth year
      internal medicine residents RESULTS: Based on content analysis of the discussion
      data, we identified five themes:1) Practice environment including acuity of
      practice, ability to do procedures, lifestyle, job prospects and income 2)
      Exposure in rotations and to role models 3) Interest in subspecialty's patient
      population and common diseases 4) Prestige and respect of subspecialty 5)
      Fellowship training environment including fellowship program resources and length
      of training CONCLUSIONS: There are a variety of factors that contribute to
      Internal Medicine residents' fellowship choice in Canada, many of which have been
      identified in previous survey studies. However, we found additional factors such
      as the resources available in a fellowship program, the prestige and respect of a
      subspecialty/career, and the recent trend towards a two-year General Internal
      Medicine fellowship in our country.

PMID- 21714922
TI  - Impact of early life exposures to geohelminth infections on the development of
      vaccine immunity, allergic sensitization, and allergic inflammatory diseases in
      children living in tropical Ecuador: the ECUAVIDA birth cohort study.
AB  - BACKGROUND: Geohelminth infections are highly prevalent infectious diseases of
      childhood in many regions of the Tropics, and are associated with significant
      morbidity especially among pre-school and school-age children. There is growing
      concern that geohelminth infections, particularly exposures occurring during
      early life in utero through maternal infections or during infancy, may affect
      vaccine immunogenicity in populations among whom these infections are endemic.
      Further, the low prevalence of allergic disease in the rural Tropics has been
      attributed to the immune modulatory effects of these infections and there is
      concern that widespread use of anthelmintic treatment in high-risk groups may be
      associated with an increase in the prevalence of allergic diseases. Because the
      most widely used vaccines are administered during the first year of life and the
      antecedents of allergic disease are considered to occur in early childhood, the
      present study has been designed to investigate the impact of early exposures to
      geohelminths on the development of protective immunity to vaccines, allergic
      sensitization, and allergic disease. METHODS/DESIGN: A cohort of 2,403 neonates
      followed up to 8 years of age. Primary exposures are infections with geohelminth
      parasites during the last trimester of pregnancy and the first 2 years of life.
      Primary study outcomes are the development of protective immunity to common
      childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B,
      tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the
      development of eczema by 3 years of age, the development of allergen skin test
      reactivity at 5 years of age, and the development of asthma at 5 and 8 years of
      age. Potential immunological mechanisms by which geohelminth infections may
      affect the study outcomes will be investigated also. DISCUSSION: The study will
      provide information on the potential effects of early exposures to geohelminths
      (during pregnancy and the first 2 years of life) on the development of vaccine
      immunity and allergy. The data will inform an ongoing debate of potential effects
      of geohelminths on child health and will contribute to policy decisions on new
      interventions designed to improve vaccine immunogenicity and protect against the
      development of allergic diseases. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN41239086.

PMID- 21714923
TI  - ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride
      levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial.
AB  - BACKGROUND: Elevated triglyceride levels are a risk factor for cardiovascular
      disease. Angiopoietin-like protein 4 (Angptl4) is a metabolic factor that raises
      plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). In non
      diabetic individuals, the ANGPTL4 coding variant E40K has been associated with
      lower plasma triglyceride levels while the T266M variant has been associated with
      more modest effects on triglyceride metabolism. The objective of this study was
      to determine whether ANGPTL4 E40K and T266M are associated with triglyceride
      levels in the setting of obesity and T2D, and whether modification of
      triglyceride levels by these genetic variants is altered by a lifestyle
      intervention designed to treat T2D. METHODS: The association of ANGPTL4 E40K and
      T266M with fasting triglyceride levels was investigated in 2,601 participants
      from the Look AHEAD Clinical Trial, all of whom had T2D and were at least
      overweight. Further, we tested for an interaction between genotype and treatment
      effects on triglyceride levels. RESULTS: Among non-Hispanic White Look AHEAD
      participants, ANGPTL4 K40 carriers had mean triglyceride levels of 1.61 +/- 0.62
      mmol/L, 0.33 mmol/L lower than E40 homozygotes (p = 0.001). Individuals
      homozygous for the minor M266 allele (MAF 30%) had triglyceride levels of 1.75 +/
      0.58 mmol/L, 0.24 mmol/L lower than T266 homozygotes (p = 0.002). The
      association of the M266 with triglycerides remained significant even after
      removing K40 carriers from the analysis (p = 0.002). There was no interaction
      between the weight loss intervention and genotype on triglyceride levels.
      CONCLUSIONS: This is the first study to demonstrate that the ANGPTL4 E40K and
      T266M variants are associated with lower triglyceride levels in the setting of
      T2D. In addition, our findings demonstrate that ANGPTL4 genotype status does not
      alter triglyceride response to a lifestyle intervention in the Look AHEAD study.

PMID- 21714924
TI  - Overexpression and purification of U24 from human herpesvirus type-6 in E. coli:
      unconventional use of oxidizing environments with a maltose binding protein
      hexahistine dual tag to enhance membrane protein yield.
AB  - BACKGROUND: Obtaining membrane proteins in sufficient quantity for biophysical
      study and biotechnological applications has been a difficult task. Use of the
      maltose binding protein/hexahistidine dual tag system with E.coli as an
      expression host is emerging as a high throughput method to enhance membrane
      protein yield, solubility, and purity, but fails to be effective for certain
      proteins. Optimizing the variables in this system to fine-tune for efficiency can
      ultimately be a daunting task. To identify factors critical to success in this
      expression system, we have selected to study U24, a novel membrane protein from
      Human Herpesvirus type-6 with potent immunosuppressive ability and a possible
      role in the pathogenesis of the disease multiple sclerosis. RESULTS: We expressed
      full-length U24 as a C-terminal fusion to a maltose binding protein/hexahistidine
      tag and examined the effects of temperature, growth medium type, cell strain
      type, oxidizing vs. reducing conditions and periplasmic vs. cytoplasmic
      expression location. Temperature appeared to have the greatest effect on yield;
      at 37 degrees C full-length protein was either poorly expressed (periplasm) or
      degraded (cytoplasm) whereas at 18 degrees C, expression was improved especially
      in the periplasm of C41(DE3) cells and in the cytoplasm of oxidizing
      Deltatrx/Deltagor mutant strains, Origami 2 and SHuffle. Expression of the fusion
      protein in these strains were estimated to be 3.2, 5.3 and 4.3 times greater,
      respectively, compared to commonly-used BL21(DE3) cells. We found that U24 is
      isolated with an intramolecular disulfide bond under these conditions, and we
      probed whether this disulfide bond was critical to high yield expression of full
      length protein. Expression analysis of a C21SC37S cysteine-free mutant U24
      demonstrated that this disulfide was not critical for full-length protein
      expression, but it is more likely that strained metabolic conditions favour
      factors which promote protein expression. This hypothesis is supported by the
      fact that use of minimal media could enhance protein production compared to
      nutrient-rich LB media. CONCLUSIONS: We have found optimal conditions for
      heterologous expression of U24 from Human Herpesvirus type-6 in E.coli and have
      demonstrated that milligram quantities of pure protein can be obtained. Strained
      metabolic conditions such as low temperature, minimal media and an oxidizing
      environment appeared essential for high-level, full-length protein production and
      this information may be useful for expressing other membrane proteins of
      interest.

PMID- 21714925
TI  - Barriers to primary care responsiveness to poverty as a risk factor for health.
AB  - BACKGROUND: Poverty is widely recognized as a major determinant of poor health,
      and this link has been extensively studied and verified. Despite the strong
      evidentiary link, little work has been done to determine what primary care health
      providers can do to address their patients' income as a risk to their health.
      This qualitative study explores the barriers to primary care responsiveness to
      poverty as a health issue in a well-resourced jurisdiction with near-universal
      health care insurance coverage. METHODS: One to one interviews were conducted
      with twelve experts on poverty and health in primary care in Ontario, Canada.
      Participants included family physicians, specialist physicians, nurse
      practitioners, community workers, advocates, policy experts and researchers. The
      interviews were analysed for anticipated and emergent themes. RESULTS: This study
      reveals provider- and patient-centred structural, attitudinal, and knowledge
      based barriers to addressing poverty as a risk to health. While many of its
      findings reinforce previous work in this area, this study's findings point to a
      number of areas front line primary care providers could target to address their
      patients' poverty. These include a lack of provider understanding of the lived
      reality of poverty, leading to a failure to collect adequate data about patients'
      social circumstances, and to the development of inappropriate care plans.
      Participants also pointed to prejudicial attitudes among providers, a failure of
      primary care disciplines to incorporate approaches to poverty as a standard of
      care, and a lack of knowledge of concrete steps providers can take to address
      patients' poverty. CONCLUSIONS: While this study reinforces, in a well-resourced
      jurisdiction such as Ontario, the previously reported existence of significant
      barriers to addressing income as a health issue within primary care, the findings
      point to the possibility of front line primary care providers taking direct steps
      to address the health risks posed by poverty. The consistent direction and
      replicability of these findings point to a refocusing of the research agenda
      toward an examination of interventions to decrease the health impacts of poverty.

PMID- 21714926
TI  - The psychiatric case register middle Netherlands.
AB  - BACKGROUND: The Psychiatric Case Register Middle Netherlands (PCR-MN) registers
      the mental healthcare consumption of over Dutch 760,000 inhabitants in the centre
      of the Netherlands. In 2010 the follow-up period was over ten years. In this
      paper we describe the content, aims and research potential of this case register.
      DESCRIPTION: All mental healthcare institutions in the middle-western part of the
      province of Utrecht participate in the PCR-MN case register. All in- and out
      patients treated in these institutions have been included in the database from
      the period 2000 to 2010. Diagnosis according to DSM-IV on axis I to IV, visits to
      in- and out-patient clinics and basic demographics are recorded. A major
      advantage of this register is the possibility to link patients anonymously from
      the PCR-MN cohort to other databases to analyze relationships with determinants
      and outcomes, such as somatic healthcare consumption, mortality, and
      demographics, which further increases the research potential CONCLUSIONS: The PCR
      MN database has a large potential for scientific research because of its size,
      duration of follow-up and ability to link with additional databases, and is
      accessible for academic researchers.

PMID- 21714927
TI  - Racial variation in lipoprotein-associated phospholipase A2 in older adults.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor of
      cardiovascular events that has been shown to vary with race. The objective of
      this study was to examine factors associated with this racial variation. METHODS:
      We measured Lp-PLA2 mass and activity in 714 healthy older adults with no
      clinical coronary heart disease and not taking dyslipidemia medication. We
      evaluated the association between race and Lp-PLA2 mass and activity levels after
      adjustment for various covariates using multivariable linear regression. These
      covariates included age, sex, diabetes, hypertension, body mass index, lipid
      measurements, C-reactive protein, smoking status, physical activity, diet,
      income, and education level. We further examined genetic covariates that included
      three single nucleotide polymorphisms shown to be associated with Lp-PLA2
      activity levels. RESULTS: The mean age was 66 years. Whites had the highest Lp
      PLA2 mass and activity levels, followed by Hispanics and Asians, and then African
      Americans; in age and sex adjusted analyses, these differences were significant
      for each non-White race as compared to Whites (p < 0.0001). For example, African
      Americans were predicted to have a 55.0 ng/ml lower Lp-PLA2 mass and 24.7 nmol/ml
      min lower activity, compared with Whites, independent of age and sex (p <
      0.0001). After adjustment for all covariates, race remained significantly
      correlated with Lp-PLA2 mass and activity levels (p < 0.001) with African
      Americans having 44.8 ng/ml lower Lp-PLA2 mass and 17.3 nmol/ml-min lower
      activity compared with Whites (p < 0.0001). CONCLUSION: Biological, lifestyle,
      demographic, and select genetic factors do not appear to explain variations in Lp
      PLA2 mass and activity levels between Whites and non-Whites, suggesting that Lp
      PLA2 mass and activity levels may need to be interpreted differently for various
      races.

PMID- 21714928
TI  - How Can the Evidence from Global Large-scale Clinical Trials for Cardiovascular
      Diseases be Improved?
AB  - BACKGROUND: Clinical investigations are important for obtaining evidence to
      improve medical treatment. Large-scale clinical trials with thousands of
      participants are particularly important for this purpose in cardiovascular
      diseases. Conducting large-scale clinical trials entails high research costs.
      This study sought to investigate global trends in large-scale clinical trials in
      cardiovascular diseases. FINDINGS: We searched for trials using
      clinicaltrials.gov (URL: http://www.clinicaltrials.gov/) using the key words
      'cardio' and 'event' in all fields on 10 April, 2010. We then selected trials
      with 300 or more participants examining cardiovascular diseases. The search
      revealed 344 trials that met our criteria. Of 344 trials, 71% were randomized
      controlled trials, 15% involved more than 10,000 participants, and 59% were
      funded by industry. In RCTs whose results were disclosed, 55% of industry-funded
      trials and 25% of non-industry funded trials reported statistically significant
      superiority over control (p = 0.012, 2-sided Fisher's exact test). CONCLUSIONS:
      Our findings highlighted concerns regarding potential bias related to funding
      sources, and that researchers should be aware of the importance of trial
      information disclosures and conflicts of interest. We should keep considering
      management and training regarding information disclosures and conflicts of
      interest for researchers. This could lead to better clinical evidence and further
      improvements in the development of medical treatment worldwide.

PMID- 21714929
TI  - SeqGene: a comprehensive software solution for mining exome- and transcriptome-
      sequencing data.
AB  - BACKGROUND: The popularity of massively parallel exome and transcriptome
      sequencing projects demands new data mining tools with a comprehensive set of
      features to support a wide range of analysis tasks. RESULTS: SeqGene, a new data
      mining tool, supports mutation detection and annotation, dbSNP and 1000 Genome
      data integration, RNA-Seq expression quantification, mutation and coverage
      visualization, allele specific expression (ASE), differentially expressed genes
      (DEGs) identification, copy number variation (CNV) analysis, and gene expression
      quantitative trait loci (eQTLs) detection. We also developed novel methods for
      testing the association between SNP and expression and identifying genotype
      controlled DEGs. We showed that the results generated from SeqGene compares
      favourably to other existing methods in our case studies. CONCLUSION: SeqGene is
      designed as a general-purpose software package. It supports both paired-end reads
      and single reads generated on most sequencing platforms; it runs on all major
      types of computers; it supports arbitrary genome assemblies for arbitrary
      organisms; and it scales well to support both large and small scale sequencing
      projects. The software homepage is http://seqgene.sourceforge.net.

PMID- 21714930
TI  - Artesunate potentiates antibiotics by inactivating heme-harbouring bacterial
      nitric oxide synthase and catalase.
AB  - BACKGROUND: A current challenge of coping with bacterial infection is that
      bacterial pathogens are becoming less susceptible to or more tolerant of commonly
      used antibiotics. It is urgent to work out a practical solution to combat the
      multidrug resistant bacterial pathogens. FINDINGS: Oxidative stress-acclimatized
      bacteria thrive in rifampicin by generating antibiotic-detoxifying nitric oxide
      (NO), which can be repressed by artesunate or an inhibitor of nitric oxide
      synthase (NOS). Suppressed bacterial proliferation correlates with mitigated NO
      production upon the combined treatment of bacteria by artesunate with
      antibiotics. Detection of the heme-artesunate conjugate and accordingly declined
      activities of heme-harbouring bacterial NOS and catalase indicates that
      artesunate renders bacteria susceptible to antibiotics by alkylating the
      prosthetic heme group of hemo-enzymes. CONCLUSIONS: By compromising NO-mediated
      protection from antibiotics and triggering harmful hydrogen peroxide burst,
      artesunate may serve as a promising antibiotic synergist for killing the
      multidrug resistant pathogenic bacteria.

PMID- 21714931
TI  - Development and validation of a short version of the Partnership Self-Assessment
      Tool (PSAT) among professionals in Dutch disease-management partnerships.
AB  - BACKGROUND: The extent to which partnership synergy is created within quality
      improvement programmes in the Netherlands is unknown. In this article, we
      describe the psychometric testing of the Partnership Self-Assessment Tool (PSAT)
      among professionals in twenty-two disease-management partnerships participating
      in quality improvement projects focused on chronic care in the Netherlands. Our
      objectives are to validate the PSAT in the Netherlands and to reduce the number
      of items of the original PSAT while maintaining validity and reliability.
      METHODS: The Dutch version of the PSAT was tested in twenty-two disease
      management partnerships with 218 professionals. We tested the instrument by means
      of structural equation modelling, and examined its validity and reliability.
      RESULTS: After eliminating 14 items, the confirmatory factor analyses revealed
      good indices of fit with the resulting 15-item PSAT-Short version (PSAT-S).
      Internal consistency as represented by Cronbach's alpha ranged from acceptable
      (0.75) for the 'efficiency' subscale to excellent for the 'leadership' subscale
      (0.87). Convergent validity was provided with high correlations of the
      partnership dimensions and partnership synergy (ranged from 0.512 to 0.609) and
      high correlations with chronic illness care (ranged from 0.447 to 0.329).
      CONCLUSION: The psychometric properties and convergent validity of the PSAT-S
      were satisfactory rendering it a valid and reliable instrument for assessing
      partnership synergy and its dimensions of partnership functioning.

PMID- 21714932
TI  - Relationship between hemoglobin A1c and cardiovascular disease in mild-to
      moderate hypercholesterolemic Japanese individuals: subanalysis of a large-scale
      randomized controlled trial.
AB  - BACKGROUND: Although the ADA/EASD/IDF International Expert Committee recommends
      using hemoglobin A1c (HbA1c) to define diabetes, the relation between HbA1c and
      cardiovascular disease (CVD) has not been thoroughly investigated. We analyzed
      this relation using clinical data on Japanese individuals with
      hypercholesterolemia. METHODS: In the large-scale MEGA Study 7832 patients aged
      40 to 70 years old with mild-to-moderate hypercholesterolemia without CVD were
      randomized to diet alone or diet plus pravastatin and followed for >5 years. In
      the present subanalysis of that study a total of 4002 patients with baseline and
      follow-up HbA1c data were stratified according to having an average HbA1c during
      the first year of follow-up <6.0%, 6.0%-<6.5%, or >= 6.5% and their subsequent 5
      year incidence rates of CVD compared according to sex, low-density lipoprotein
      cholesterol (LDL-C), and treatment arm. RESULTS: Overall, risk of CVD was
      significantly 2.4 times higher in individuals with HbA1c >= 6.5% versus <6.0%. A
      similar relation was noted in men and women (hazard ratio [HR], 2.1; p <0.01 and
      HR, 3.0; p <0.01, respectively) and was regardless of treatment arm (diet alone
      group: HR, 2.2; p <0.001; diet plus pravastatin group: HR, 1.8; p = 0.02). Spline
      curves showed a continuous risk increase according to HbA1c level in all
      subpopulations studied. CONCLUSIONS: In hypercholesterolemic individuals the risk
      of CVD increases linearly with HbA1c level. This significant contribution by
      elevated HbA1c to increased CVD is independent of pravastatin therapy, and thus
      requires appropriate HbA1c management in addition to lipids reduction.

PMID- 21714933
TI  - Associations between proinflammatory cytokines in the synovial fluid and
      radiographic grading and pain-related scores in 47 consecutive patients with
      osteoarthritis of the knee.
AB  - BACKGROUND: One of the sources of knee pain in osteoarthritis (OA) is believed to
      be related to local chronic inflammation of the knee joints, which involves the
      production of inflammatory cytokines such as tumor necrosis factor alpha
      (TNFalpha), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial
      membrane, and these cytokines are believed to promote pathological OA. In the
      present study, correlations between proinflammatory cytokines in knee synovial
      fluid and radiographic changes and functional scores and pain scores among OA
      patients were examined. METHODS: Synovial fluid was harvested from the knees of
      47 consecutive OA patients, and the levels of TNFalpha, IL-6, and NGF were
      measured using enzyme-linked immunosorbent assays. Osteoarthritic knees were
      classified using Kellgren-Lawrence (KL) grading (1-4). The Western Ontario and
      McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported
      physical function, pain, and stiffness. RESULTS: TNFalpha and IL-6 were
      detectable in knee synovial, whereas NGF was not. TNFalpha was not correlated
      with the KL grade, whereas IL-6 had a significantly negative correlation. We
      observed differences in the correlations between TNFalpha and IL-6 with WOMAC
      scores and their subscales (pain, stiffness, and physical function). TNFalpha
      exhibited a significant correlation with the total score and its 3 subscales,
      whereas IL-6 exhibited a moderately significant negative correlation only with
      the subscale of stiffness. CONCLUSIONS: The present study demonstrated that the
      concentrations of proinflammatory cytokines are correlated with KL grades and
      WOMAC scores in patients with knee OA. Although TNFalpha did not have a
      significant correlation with the radiographic grading, it was significantly
      associated with the WOMAC score. IL-6 had a significant negative correlation with
      the KL grading, whereas it had only a weakly significant correlation with the
      subscore of stiffness. The results suggest that these cytokines play a role in
      the pathogenesis of synovitis in osteoarthritic knees in different ways: TNFalpha
      is correlated with pain, whereas IL-6 is correlated with joint function.

PMID- 21714934
TI  - Periostin: a promising target of therapeutical intervention for prostate cancer.
AB  - BACKGROUND: In our recent study, Periostin was up-regulated in prostate
      cancer(PCa) compared with benign prostate hyperplasia (BPH) by proteomics
      analysis of prostate biopsies. We investigated the effect of sliencing Periostin
      by RNA interference (RNAi) on the proliferation and migration of PCa LNCap cell
      line. METHODS: All the prostate biopsies from PCa, BPH and BPH with local
      prostatic intraepithelial neoplasm(PIN) were analyzed by iTRAQ(Isobaric tags for
      relative and absolute quantification) technology. Western blotting and
      immunohistochemical staining were used to verify Periostin expression in the
      tissues of PCa. Periostin expression in different PCa cell lines was determined
      by immunofluorescence staining, western blotting and reverse transcription PCR(RT
      PCR). The LNCap cells with Periostin expression were used for transfecting shRNA
      Periostin lentiviral particles. The efficancy of transfecting shRNA lentiviral
      particles was evaluated by immunofluorescence, western blotting and Real-time
      PCR. The effect of silencing Periostin expression by RNAi on proliferation of
      LNCap cells was determined by MTT assay and tumor xenografts. The tissue slices
      from theses xenografts were analyzed by hematoxylin and eosin(HE) staining. The
      expression of Periostin in the xenografts was deteminned by Immunohistochemical
      staining and western blotting. The migration of LNCap cells after silencing
      Periostin gene expression were analyzed in vitro. RESULTS: Periostin as the
      protein of interest was shown 9.12 fold up-regulation in PCa compared with BPH.
      The overexpression of Periostin in the stroma of PCa was confirmed by western
      blotting and immunohistochemical staining. Periostin was only expressed in PCa
      LNCap cell line. Our results indicated that the transfection ratio was more than
      90%. As was expected, both the protein level and mRNA level of Periostin in the
      stably expressing shRNA-Periostin LNCap cells were significantly reduced. The
      stably expressing shRNA-Periostin LNCap cells growed slowly in vitro and in vivo.
      The tissues of xenografts as PCa were verificated by HE staining. Additionally,
      the weak positive Periostin expressed tumor cells could be seen in the tissues of
      6 xenografts from the group of down-regulated Periostin LNCap cells which had a
      significant decrease of the amount of Periostin compared to the other two group.
      Furthermore, our results demonstrated that sliencing Periostin could inhibit
      migration of LNCap cells in vitro. CONCLUSIONS: Our data indicates that Periostin
      as an up-regulated protein in PCa may be a promising target of therapeutical
      intervention for PCa in future.

PMID- 21714935
TI  - Simultaneous in-field boost for patients with 1 to 4 brain metastasis/es treated
      with volumetric modulated arc therapy: a prospective study on quality-of-life.
AB  - PURPOSE: To assess treatment toxicity and patients' survival/quality of life
      (QoL) after volumetric modulated arc therapy (VMAT) with simultaneous in-field
      boost (SIB) for cancer patients with 1 - 4 brain metastases (BM) treated with or
      without surgery. METHODS AND MATERIALS: Between March and December 2010, 29 BM
      patients (total volume BM, < 40 cm3) aged < 80 years, KPS >= 70, RPA < III were
      included in this prospective trial. Whole brain VMAT (30 Gy) and a SIB to the BM
      (40 Gy) was delivered in 10 fraction. Mean age was 62.1 +/- 8.5 years. Fifteen
      (51.7%) underwent surgery. KPS and MMSE were prospectively assessed. A self
      assessed questionnaire was used to assess the QoL (EORTC QLQ-C30 with -BN20
      module). RESULTS: As of April 2011 and after a mean FU of 5.4 +/- 2.8 months, 14
      (48.3%) patients died. The 6-month overall survival was 55.1%. Alopecia was only
      observed in 9 (31%) patients. In 3-month survivors, KPS was significantly (p =
      0.01) decreased. MMSE score remained however stable (p = 0.33). Overall, QoL did
      decrease after VMAT. The mean QLQ-C30 global health status (p = 0.72) and
      emotional functional (p = 0.91) scores were decreased (low QoL). Physical (p =
      0.05) and role functioning score (p = 0.01) were significantly worse and rapidly
      decreased during treatment. The majority of BN20 domains and single items
      worsened 3 months after VMAT except headaches (p = 0.046) and bladder control (p
      = 0.26) which improved. CONCLUSIONS: The delivery of 40 Gy in 10 fractions to 1 -
      4 BM using VMAT was achieved with no significant toxicity. QoL, performance
      status, but not MMSE, was however compromised 3 months after treatment in this
      selected cohort of BM patients.

PMID- 21714936
TI  - How stands the Tree of Life a century and a half after The Origin?
AB  - We examine the Tree of Life (TOL) as an evolutionary hypothesis and a heuristic.
      The original TOL hypothesis has failed but a new "statistical TOL hypothesis" is
      promising. The TOL heuristic usefully organizes data without positing fundamental
      evolutionary truth.

PMID- 21714937
TI  - From the scala naturae to the symbiogenetic and dynamic tree of life.
AB  - All living beings on Earth, from bacteria to humans, are connected through
      descent from common ancestors and represent the summation of their corresponding,
      ca. 3500 million year long evolutionary history. However, the evolution of
      phenotypic features is not predictable, and biologists no longer use terms such
      as "primitive" or "perfect organisms". Despite these insights, the Bible-based
      concept of the so-called "ladder of life" or Scala Naturae, i.e., the idea that
      all living beings can be viewed as representing various degrees of "perfection",
      with humans at the very top of this biological hierarchy, was popular among
      naturalists until ca. 1850 (Charles Bonnet, Jean Lamarck and others). Charles
      Darwin is usually credited with the establishment of a branched evolutionary
      "Tree of Life". This insight of 1859 was based on his now firmly corroborated
      proposals of common ancestry and natural selection. In this article I argue that
      Darwin was still influenced by "ladder thinking", a theological view that
      prevailed throughout the 19th century and is also part of Ernst Haeckel's famous
      Oak tree (of Life) of 1866, which is, like Darwin's scheme, static. In 1910,
      Constantin Mereschkowsky proposed an alternative, "anti-selectionist" concept of
      biological evolution, which became known as the symbiogenesis-theory. According
      to the symbiogenesis-scenario, eukaryotic cells evolved on a static Earth from
      archaic prokaryotes via the fusion and subsequent cooperation of certain
      microbes. In 1929, Alfred Wegener published his theory of continental drift,
      which was later corroborated, modified and extended. The resulting theory of
      plate tectonics is now the principal organizing concept of geology. Over millions
      of years, plate tectonics and hence the "dynamic Earth" has caused destructive
      volcanic eruptions and earthquakes. At the same time, it created mountain ranges,
      deep oceans, novel freshwater habitats, and deserts. As a result, these geologic
      processes destroyed numerous populations of organisms, and produced the
      environmental conditions for new species of animals, plants and microbes to adapt
      and evolve. In this article I propose a tree-like "symbiogenesis, natural
      selection, and dynamic Earth (synade)-model" of macroevolution that is based on
      these novel facts and data.

PMID- 21714938
TI  - Ethnicity and thrombolysis in ischemic stroke: a hospital based study in
      Amsterdam.
AB  - BACKGROUND: Ethnic differences have been reported with regard to several medical
      therapies. The aim of this study was to investigate the relation between
      ethnicity and thrombolysis in stroke patients. METHODS: Retrospective single
      centre study. Patients admitted with an ischemic stroke between 2003 and 2008
      were included. Ethnicity was determined by self-identification and stratified
      into white and non-white (all other ethnicities). The main outcome measure was
      the difference in thrombolysis rate between white and non-white patients.
      Logistic regression analysis was used to identify potential confounders of the
      relation between ethnicity and thrombolysis. RESULTS: 510 patients were included,
      392 (77%) white and 118 (23%) non-white. Non-white patients were younger (median
      69 vs. 60 years, p<0.001), had a higher blood pressure at admission (median
      systolic 150 vs. 160 mmHg, p=0.02) and a lower stroke severity (median NIHSS 5
      vs. 4, p=0.04). Non-white patients were significantly less often treated with
      thrombolysis compared to white patients (odds ratio 0.34, 95% CI 0.17-0.71),
      which was partly explained by a later arrival at the hospital. After adjustment
      for potential confounders (late arrival, age, blood pressure above upper limit
      for thrombolysis, and oral anticoagulation use), a trend towards a lower
      thrombolysis rate in non-whites remained (adjusted odds ratio 0.38, 95% CI 0.13
      to 1.16). CONCLUSIONS: Non-white stroke patients less often received thrombolysis
      than white patients, partly as a result of a delay in presentation. In this
      single centre study, potential bias due to hospital differences or insurance
      status could be ruled out as a cause. The magnitude of the difference is
      worrisome and requires further investigation. Modifiable causes, such as patient
      delay, awareness of stroke symptoms, language barriers and treatment of
      cardiovascular risk factors, should be addressed specifically in these ethnic
      groups in future stroke campaigns.

PMID- 21714939
TI  - Telling the whole story in a 10,000-genome world.
AB  - BACKGROUND: Genome sequencing has revolutionized our view of the relationships
      among genomes, particularly in revealing the confounding effects of lateral
      genetic transfer (LGT). Phylogenomic techniques have been used to construct
      purported trees of microbial life. Although such trees are easily interpreted and
      allow the use of a subset of genomes as "proxies" for the full set, LGT and other
      phenomena impact the positioning of different groups in genome trees, confounding
      and potentially invalidating attempts to construct a phylogeny-based taxonomy of
      microorganisms. Network and graph approaches can reveal complex sets of
      relationships, but applying these techniques to large data sets is a significant
      challenge. Notwithstanding the question of what exactly it might represent,
      generating and interpreting a Tree or Network of All Genomes will only be
      feasible if current algorithms can be improved upon. RESULTS: Complex
      relationships among even the most-similar genomes demonstrate that proxy-based
      approaches to simplifying large sets of genomes are not alone sufficient to solve
      the analysis problem. A phylogenomic analysis of 1173 sequenced bacterial and
      archaeal genomes generated phylogenetic trees for 159,905 distinct homologous
      gene sets. The relationships inferred from this set can be heavily dependent on
      the inclusion of other taxa: for example, phyla such as Spirochaetes,
      Proteobacteria and Firmicutes are recovered as cohesive groups or split depending
      on the presence of other specific lineages. Furthermore, named groups such as
      Acidithiobacillus, Coprothermobacter and Brachyspira show a multitude of
      affiliations that are more consistent with their ecology than with small subunit
      ribosomal DNA-based taxonomy. Network and graph representations can illustrate
      the multitude of conflicting affinities, but all methods impose constraints on
      the input data and create challenges of construction and interpretation.
      CONCLUSIONS: These complex relationships highlight the need for an inclusive
      approach to genomic data, and current methods with minor alterations will likely
      scale to allow the analysis of data sets with 10,000 or more genomes. The main
      challenges lie in the visualization and interpretation of genomic relationships,
      and the redefinition of microbial taxonomy when subsets of genomic data are so
      evidently in conflict with one another, and with the "canonical" molecular
      taxonomy.

PMID- 21714940
TI  - Vaccination with dengue virus-like particles induces humoral and cellular immune
      responses in mice.
AB  - BACKGROUND: The incidence of dengue, an infectious disease caused by dengue virus
      (DENV), has dramatically increased around the world in recent decades and is
      becoming a severe public health threat. However, there is currently no specific
      treatment for dengue fever, and licensed vaccine against dengue is not available.
      Vaccination with virus-like particles (VLPs) has shown considerable promise for
      many viral diseases, but the effect of DENV VLPs to induce specific immune
      responses has not been adequately investigated. RESULTS: By optimizing the
      expression plasmids, recombinant VLPs of four antigenically different DENV
      serotypes DENV1-4 were successfully produced in 293T cells. The vaccination
      effect of dengue VLPs in mice showed that monovalent VLPs of each serotype
      stimulated specific IgG responses and potent neutralizing antibodies against
      homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and
      neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination
      with monovalent or tetravalent VLPs resulted in the induction of specific
      cytotoxic T cell responses. CONCLUSIONS: Mammalian cell expressed dengue VLPs are
      capable to induce VLP-specific humoral and cellular immune responses in mice, and
      being a promising subunit vaccine candidate for prevention of dengue virus
      infection.

PMID- 21714941
TI  - Energetics and genetics across the prokaryote-eukaryote divide.
AB  - BACKGROUND: All complex life on Earth is eukaryotic. All eukaryotic cells share a
      common ancestor that arose just once in four billion years of evolution.
      Prokaryotes show no tendency to evolve greater morphological complexity, despite
      their metabolic virtuosity. Here I argue that the eukaryotic cell originated in a
      unique prokaryotic endosymbiosis, a singular event that transformed the selection
      pressures acting on both host and endosymbiont. RESULTS: The reductive evolution
      and specialisation of endosymbionts to mitochondria resulted in an extreme
      genomic asymmetry, in which the residual mitochondrial genomes enabled the
      expansion of bioenergetic membranes over several orders of magnitude, overcoming
      the energetic constraints on prokaryotic genome size, and permitting the host
      cell genome to expand (in principle) over 200,000-fold. This energetic
      transformation was permissive, not prescriptive; I suggest that the actual
      increase in early eukaryotic genome size was driven by a heavy early bombardment
      of genes and introns from the endosymbiont to the host cell, producing a high
      mutation rate. Unlike prokaryotes, with lower mutation rates and heavy selection
      pressure to lose genes, early eukaryotes without genome-size limitations could
      mask mutations by cell fusion and genome duplication, as in allopolyploidy,
      giving rise to a proto-sexual cell cycle. The side effect was that a large number
      of shared eukaryotic basal traits accumulated in the same population, a sexual
      eukaryotic common ancestor, radically different to any known prokaryote.
      CONCLUSIONS: The combination of massive bioenergetic expansion, release from
      genome-size constraints, and high mutation rate favoured a protosexual cell cycle
      and the accumulation of eukaryotic traits. These factors explain the unique
      origin of eukaryotes, the absence of true evolutionary intermediates, and the
      evolution of sex in eukaryotes but not prokaryotes. REVIEWERS: This article was
      reviewed by: Eugene Koonin, William Martin, Ford Doolittle and Mark van der
      Giezen. For complete reports see the Reviewers' Comments section.

PMID- 21714943
TI  - Prevalence of Helicobacter pylori in HIV-infected, HAART-naive Ugandan children:
      a hospital-based survey.
AB  - BACKGROUND: The aim of this survey was to determine the prevalence of and factors
      associated with Helicobacter pylori (H. pylori) colonization in HIV-infected,
      highly active antiretroviral therapy-naive Ugandan children aged 0-12 years.
      METHODS: In a hospital-based survey, 236 HIV-infected children were tested for H.
      pylori colonization using a faecal antigen test. A standardized interview with
      socio-demographic information and medical history was used to assess risk
      factors. A cluster of differentiation 4 (CD4) cell percentage was prevalent in
      most children. RESULTS: The overall prevalence of H. pylori in the HIV-infected
      children was 22.5%. Age-specific prevalence was as follows: up to one year,
      14.7%; 1-3 years, 30.9%; and 3-12 years, 20.7%. HIV-infected children who were
      more seriously affected by their disease (low CD4 cell percentage or WHO clinical
      stage II-IV) were less likely to be colonized with H. pylori. There was a trend
      for a lower prevalence of H. pylori in children who had taken antibiotics for the
      preceding two weeks (21.6%) than in those who had not taken antibiotics (35.7%).
      There was no statistically significant difference in prevalence by gender,
      housing, congested living, education of the female caretaker, drinking water or
      toilet facilities. CONCLUSIONS: HIV-infected, HAART-naive Ugandan children had a
      lower prevalence of H. pylori colonization compared with apparently healthy
      Ugandan children (44.3%). Children with a low CD4 cell percentage and an advanced
      clinical stage of HIV had an even lower risk of H. pylori colonization. Treatment
      with antibiotics due to co-morbidity with infectious diseases is a possible
      explanation for the relatively low prevalence.

PMID- 21714942
TI  - Early evolution without a tree of life.
AB  - Life is a chemical reaction. Three major transitions in early evolution are
      considered without recourse to a tree of life. The origin of prokaryotes required
      a steady supply of energy and electrons, probably in the form of molecular
      hydrogen stemming from serpentinization. Microbial genome evolution is not a
      treelike process because of lateral gene transfer and the endosymbiotic origins
      of organelles. The lack of true intermediates in the prokaryote-to-eukaryote
      transition has a bioenergetic cause.

PMID- 21714944
TI  - Robustness and fault tolerance make brains harder to study.
AB  - Brains increase the survival value of organisms by being robust and fault
      tolerant. That is, brain circuits continue to operate as the organism needs, even
      when the circuit properties are significantly perturbed. Kispersky and
      colleagues, in a recent paper in Neural Systems & Circuits, have found that
      Granger Causality analysis, an important method used to infer circuit connections
      from the behavior of neurons within the circuit, is defeated by the mechanisms
      that give rise to this robustness and fault tolerance.

PMID- 21714945
TI  - Amblyopia.
AB  - INTRODUCTION: Amblyopia is commonly associated with squint (strabismus) or
      refractive errors resulting in different visual inputs to each eye during the
      sensitive period of visual development (<7-8 years of age). The cumulative
      incidence is estimated at 2% to 4% in children aged up to 15 years. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of interventions to detect amblyopia
      early? What are the effects of medical treatments for amblyopia? We searched:
      Medline, Embase, The Cochrane Library, and other important databases up to May
      2010 (Clinical Evidence reviews are updated periodically; please check our
      website for the most up-to-date version of this review). We included harms alerts
      from relevant organisations, such as the US Food and Drug Administration (FDA)
      and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS:
      We found 33 systematic reviews, RCTs, or observational studies that met our
      inclusion criteria. We performed a GRADE evaluation of the quality of evidence
      for interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions: active
      vision therapy; glasses alone or with occlusion; or penalisation to treat
      amblyopia; and screening to detect amblyopia early.

PMID- 21714946
TI  - Salicylic acid enhances Staphylococcus aureus extracellular adhesin protein
      expression.
AB  - One of the virulence factors required by Staphylococcus aureus at the early
      stages of infection is Eap, a secreted adhesin that binds many host proteins and
      is upregulated by the two-component regulatory system saeRS. The S. aureus Newman
      strain harbors a mutation in saeS that is thought to be responsible for the high
      level of Eap expression in this strain. This study was designed to ascertain
      whether salicylic acid (SAL) affects the expression of Eap and the
      internalization of S. aureus into epithelial cells. The strain Newman treated
      with SAL exhibited increased levels of eap transcription and protein expression.
      Furthermore, SAL treatment increased the eap promoter activity. SAL treatment
      enhanced Eap expression in the Newman and in other S. aureus strains that do not
      carry the mutation in saeS. Internalization of S. aureus eap and sae mutants into
      the MAC-T epithelial cells was significantly decreased compared with the wild
      type counterparts. In conclusion, we demonstrated that a low concentration of SAL
      increased S. aureus Eap expression possibly due to enhancement of sae. SAL may
      create the conditions for S. aureus persistence in the host, not only by
      decreasing the capsular polysaccharide expression as shown before, but also by
      enhancing Eap expression.

PMID- 21714947
TI  - Effect of cholesterol on mortality and quality of life up to a 46-year follow-up.
AB  - The effect of cholesterol level on the health of older people is a matter of
      debate, probably because of the bidirectional association. We investigated this
      paradox in a long-term study. The baseline assessments of the Helsinki
      Businessmen Study (a cohort of mainly business executives, born 1919 to 1934)
      included the total cholesterol value and other cardiovascular risk factors from
      1964 to 1973. These men were followed up for <=46 years (through January 2010).
      During the follow-up period, the cholesterol value was assessed by self-report in
      2000 (n = 1,292). Mortality was ascertained from the national registers,
      symptoms, and health-related quality of life with RAND-36 from questionnaires in
      2000. A total of 3,277 healthy men without chronic diseases at baseline were
      included in the analyses. The median total cholesterol concentration at baseline
      was 6.5 mmol/L (251 mg/dl) (interquartile range 5.8 to 7.3 mmol/L, 224 to 282
      mg/dl) and, in 2000, was 5.2 mmol/L (201 mg/dl) (interquartile range 4.6 to 5.9
      mmol/L, 178 to 228 mg/dl). During the follow-up period, 1,773 men (54%) died. A
      strong and graded relation was found between the cholesterol level and total
      mortality, with the men with a cholesterol level <=4 mmol/L (154 mg/dl) having
      the lowest mortality. In all, the men with the lowest cholesterol gained the most
      life years. However, no association was found with the cholesterol level in 2000
      (when 16% were using statins) and subsequent mortality. The lowest (<=4 mmol/L)
      cholesterol value in midlife also predicted a higher score in the physical
      functioning scale of RAND-36 in old age. In conclusion, a low total cholesterol
      value in midlife predicts both better survival and better physical functioning in
      old age.

PMID- 21714948
TI  - Risk stratification in the setting of non-ST elevation acute coronary syndromes
      1999-2007.
AB  - It is unclear if clinician risk stratification has changed with time. The aim of
      this study was to assess the temporal change in the concordance between patient
      presenting risk and the intensity of evidence-based therapies received for non-ST
      segment elevation acute coronary syndromes over a 9-year period. Data from 3,562
      patients with non-ST-segment elevation acute coronary syndromes enrolled in the
      Australian and New Zealand population of the Global Registry of Acute Coronary
      Events (GRACE) from 1999 to 2007 were analyzed. Patients were stratified to risk
      groups on the basis of the GRACE risk score for in-hospital mortality. Main
      outcome measures included in-hospital use of widely accepted evidence-based
      medications, investigations, and procedures. Invasive management was consistently
      higher in low-risk patients than in intermediate- or high-risk patients (coronary
      angiography 66.7% vs 63.5% vs 35.3%, p <0.001; percutaneous coronary intervention
      31.1% vs 22.0% vs 12.9%, p <0.001). Absolute rates of angiography and
      percutaneous coronary intervention in the high-risk group remained 24% and 15%
      lower compared to the low-risk group in the most recent time period (2005 to
      2007). In-hospital use of thienopyridine, low-molecular weight heparin, and
      glycoprotein IIb/IIIa inhibitors showed a similar inverse relation with risk.
      Prescription of aspirin, beta blockers, statins, and angiotensin receptor
      blockers was inversely related to risk before 2004, although this inverse
      relation was no longer present in the most recent time period (2005 to 2007).
      Only in-hospital use of unfractionated heparin showed use concordant with patient
      risk status. In conclusion, despite an overall increase in the uptake of evidence
      based therapies, most investigations and treatments are not targeted on the basis
      of patient risk. Clinician risk stratification remains suboptimal compared to
      objective measures of patient risk.

PMID- 21714949
TI  - Prediction of response to cardiac resynchronization therapy combining two
      different three-dimensional analyses of left ventricular dyssynchrony.
AB  - Triplane tissue synchronization imaging (TSI) and real-time 3-dimensional
      echocardiography (RT3DE) provide different characterizations of left ventricular
      (LV) mechanics and dyssynchrony. Triplane TSI assesses differences in time to
      peak systolic segmental myocardial tissue velocities, whereas RT3DE evaluates
      differences in time to minimum end-systolic regional volumes. Whether an approach
      using the 2 3D techniques predicts better significant reverse remodeling after
      cardiac resynchronization therapy (CRT) remains unknown. In 166 patients (mean
      age 66 +/- 9 years, 78% men) treated with CRT, baseline LV dyssynchrony was
      assessed using RT3DE and triplane TSI. LV dyssynchrony was defined by a systolic
      dyssynchrony index >=6.4% when assessed with RT3DE and SD of time to peak
      velocity of 12 segments (Ts-SD-12) >=33 ms with triplane TSI. CRT response was
      defined by >=15% decrease in LV end-systolic volume at 6-month follow-up. Mean LV
      dyssynchrony using Ts-SD-12 was 48 +/- 26 ms and mean systolic dyssynchrony index
      was 8.51 +/- 3.81%. Response to CRT was observed in 86.3% of patients showing LV
      dyssynchrony with the 2 methods. In contrast, 97% of patients who did not show
      significant LV dyssynchrony with any of the techniques were nonresponders (p
      <0.001). Importantly, systolic dyssynchrony index and LV dyssynchrony using Ts-SD
      12 were independent predictors of response to CRT (p <0.001 for each technique).
      Assessment of LV dyssynchrony with the 2 techniques showed incremental value for
      prediction of significant LV reverse remodeling over its assessment with only 1
      technique (chi-square 90.18, p <0.001). In conclusion, the combined use of 2
      different 3D techniques to assess LV dyssynchrony permits accurate prediction of
      response to CRT.

PMID- 21714950
TI  - A regressive Meigs syndrome after definitive adnexal torsion.
AB  - The Meigs syndrome is a rare but well known syndrome in which removal of the
      tumor results in cure. We report a case of a regressive Meigs syndrome after a
      definitive adnexal torsion which highlights the major role of the vascular
      phenomena in the physiopathology of this puzzling syndrome.

PMID- 21714951
TI  - Comparing long-term survival between patients undergoing off-pump and on-pump
      coronary artery bypass graft operations.
AB  - BACKGROUND: As the population of the United States and Western Europe ages, the
      number of patients undergoing isolated coronary artery bypass grafting (CABG) for
      revascularization can be expected to increase. This study investigated long-term
      survival in patients undergoing off-pump vs on-pump CABG. METHODS: Survival was
      assessed in 8081 consecutive patients who underwent isolated CABG (732 received
      off-pump) between January 1, 1997, and December 31, 2008. A propensity-adjusted
      model controlling for preoperative risk factors identified by the Society of
      Thoracic Surgeons and other preoperative clinical and nonclinical details was
      used to assess adjusted long-term mortality differences between off-pump and on
      pump CABG. RESULTS: Ten-year unadjusted survival was 54.7% (95% confidence
      interval, 47.2% to 61.6%) in off-pump CABG patients and 62.3% (95% confidence
      interval 60.9% to 63.8%) in on-pump CABG patients. The log-rank test (p=0.012)
      indicated a significantly higher risk of death in off-pump CABG patients. After
      adjustment, the risk of death remained significantly higher in the off-pump CABG
      patients (hazard ratio, 1.18; 95% confidence interval, 1.02 to 1.38). The
      adjusted association regarding off-pump learning curve and survival was assessed
      separately and was not statistically significant (p=0.774), further validating
      our findings regarding off-pump CABG. CONCLUSIONS: After controlling for
      preoperative severity of disease and other possible confounders, the risk of long
      term mortality in patients undergoing off-pump CABG is significantly higher than
      in those undergoing on-pump CABG. For multivessel coronary disease, on-pump CABG
      might be preferable to off-pump CABG given that it may achieve a more complete
      and durable revascularization.

PMID- 21714952
TI  - Validating 'fit for duty' tests for Australian volunteer fire fighters
      suppressing bushfires.
AB  - INTRODUCTION: This study compared fire fighter's work-rates and performance
      between the Pack Hike Test (PHT), Field Walk Test (FWT) and critical bushfire
      suppression tasks. METHODS: Nineteen volunteer fire fighters undertook the PHT,
      whilst a further 11 also performed the FWT. All 30 fire fighters completed four
      critical tasks. Physical, physiological and subjective ratings were measured
      during tasks and tests. RESULTS: Peak and mean heart rate during the Hose Drag
      was lower than during the FWT. Mean velocities for the PHT and FWT were higher
      than in all tasks except Hose Drag. Finishing times in the PHT and FWT were
      strongly correlated with finishing times for three and four of the critical
      tasks. CONCLUSIONS: The PHT and FWT may be valid fit for duty tests for
      Australian rural fire fighters though the clear differences between the tests and
      some tasks may prompt fire agencies to consider other tests that more accurately
      simulate bushfire suppression work.

PMID- 21714953
TI  - Comparison of four specific dynamic office chairs with a conventional office
      chair: impact upon muscle activation, physical activity and posture.
AB  - Prolonged and static sitting postures provoke physical inactivity at VDU
      workplaces and are therefore discussed as risk factors for the musculoskeletal
      system. Manufacturers have designed specific dynamic office chairs featuring
      structural elements which promote dynamic sitting and therefore physical
      activity. The aim of the present study was to evaluate the effects of four
      specific dynamic chairs on erector spinae and trapezius EMG, postures/joint
      angles and physical activity intensity (PAI) compared to those of a conventional
      standard office chair. All chairs were fitted with sensors for measurement of the
      chair parameters (backrest inclination, forward and sideward seat pan
      inclination), and tested in the laboratory by 10 subjects performing 7
      standardized office tasks and by another 12 subjects in the field during their
      normal office work. Muscle activation revealed no significant differences between
      the specific dynamic chairs and the reference chair. Analysis of postures/joint
      angles and PAI revealed only a few differences between the chairs, whereas the
      tasks performed strongly affected the measured muscle activation, postures and
      kinematics. The characteristic dynamic elements of each specific chair yielded
      significant differences in the measured chair parameters, but these
      characteristics did not appear to affect the sitting dynamics of the subjects
      performing their office tasks.

PMID- 21714954
TI  - Evaluation of the implementation fidelity of an ergonomic training program
      designed to prevent back pain.
AB  - The aim of this study was to evaluate the implementation fidelity of a
      multidimensional ergonomic program designed to prevent back pain injuries among
      healthcare personnel. The program, provided by peer trainers included training
      intended to modify patient handling and transfer behaviour, trainee follow-up,
      prevention activities aimed at work environment improvements and follow-up
      monitors training. Two hundred twenty-one peer trainers at 139 Quebec healthcare
      institutions participated in our study. Only 61.5% were involved in training;
      most of them taught safe patient handling, positioning, transfer, and preparation
      techniques, which are the cornerstones of the program; 72.7% were involved in
      prevention activities, 46.1% in follow-up activities, and 10.7% in follow-up
      monitors training. The study results should help organizations anticipate and
      prevent potential discrepancies between prescribed and implemented programs.

PMID- 21714955
TI  - A comparison of methods for assessing the thermal insulation value of children's
      schoolwear in Kuwait.
AB  - In this study, three methods were used to determine the thermal insulation values
      of different school clothing worn by 6 to 17 year old girls and boys in Kuwait
      classrooms for both summer and winter seasons. The different clothing ensembles'
      insulations were determined by 1: measurement using adult-sized versions of the
      clothing on thermal manikins, 2: estimations from adult clothing data obtained
      from the standards tables in ISO 9920 and ASHRAE 55, and 3: calculations using a
      regression equation from McCullough et al. (1985) that was adapted to accommodate
      children's sizes for ages 6-17 years. Values for the clothing area factor, f(cl),
      were also determined by measurement and by using a prediction equation from ISO
      9920. Results in this study suggested that the clothing insulation values found
      from the measured and adapted data were similar to the adult's data in standards
      tables for the same summer and winter seasons. Further, the effect of the
      insulation values on the different scholars' age groups were investigated using
      the clothing temperature rating technique and compared to the scholars' comfort
      temperature found in recent field studies. Results showed that the temperature
      ratings of the clothing using the three methods described above are close and in
      agreement with the scholars' comfort temperature. Though estimated and measured
      f(cl) data differed, the impact on the temperature ratings was limited. An
      observed secular change in the children's heights and weights in the last few
      decades implies that, for adolescents, the children's body surface areas are
      similar to those of adults, making the use of adult clothing tables even more
      acceptable. In conclusion, this study gives some evidence to support the
      applicability of using adults' data in ASHRAE 55 and ISO 9920 standards to assess
      the thermal insulation values of different children's clothing ensembles,
      provided that careful selection of the garments, ensembles material and design
      takes place.

PMID- 21714956
TI  - Caries prevalence and periodontal status in 18th century population of Pozega
      Croatia.
AB  - OBJECTIVE: The aim was to examine dental and periodontal status of adult Croatian
      18th century population and compare the results with available literature data.
      MATERIALS AND METHODS: 104 specimens from the crypt of Pozega cathedral were
      grouped into three female and three male groups according to age. Caries was
      determined by visual inspection and dental probe. Ante and post mortem teeth
      losses were recorded. Periodontal status was determined according to the length
      of exposed tooth root from alveolar crest to cemento-enamel junction. The
      presence of dehiscences and fenestrations was recorded on facial and oral plate
      of alveolar bone. RESULTS: The whole sample exhibited ante- and post mortem teeth
      loss of 19.57% and 24.91%, respectively. The teeth most frequently lost
      postmortem were incisors. The canines were best preserved. The frequency of
      caries in both jaws was the highest in molars (26.63% in maxilla and 28.10% in
      mandible), whilst central incisors exhibited the least carious lesions (11.59 and
      1.92%). The most frequently affected surfaces were occlusal, then proximal and
      facio-oral. The percentage of teeth with either moderate or considerable bone
      loss was higher in females. The frequency of considerable bone loss increased
      significantly with age. The frequency of dehiscences was 3.11%. It was higher in
      maxilla than in the mandible. The frequency of fenestrations was 5.65% and it was
      significantly higher in maxilla. CONCLUSIONS: The results demonstrate poor oral
      health amongst 18th century population of continental Croatia, exhibiting high
      antemortem teeth loss, high periodontal disease frequency and occlusal and
      proximal caries frequency.

PMID- 21714957
TI  - Adaptation strategies of the lower extremities of patients with a transtibial or
      transfemoral amputation during level walking: a systematic review.
AB  - OBJECTIVE: To describe adaptation strategies in terms of joint power or work in
      the amputated and intact leg of patients with a transtibial (TT) or transfemoral
      (TF) amputation. DATA SOURCES: MEDLINE, CINAHL, Physiotherapy Evidence Database,
      Embase, and the Cochrane Register of Controlled Trials were searched. Studies
      were collected up to November 1, 2010. Reference lists were additionally
      scrutinized. STUDY SELECTION: Studies were included when they presented joint
      power or work and compared (1) the amputated and intact legs, (2) the amputated
      leg and a referent leg, or (3) the intact leg and a referent leg. Eligibility was
      independently assessed by 2 reviewers. A total of 13 articles were identified.
      DATA EXTRACTION: Data extraction was performed using standardized forms of the
      Cochrane Collaboration. Methodologic quality was independently assessed using the
      Downs and Black instrument by 2 reviewers. The possibility of data pooling was
      examined. Significant differences found in studies that could not be pooled are
      also presented. DATA SYNTHESIS: Significant results (P<.05). For work TT, for the
      concentric work total stance phase knee, the amputated was less than the
      intact/referent side, and the referent was less than the intact side. For the
      eccentric knee extensor (K1) phase, the amputated was less than the intact side,
      and the intact was greater than the referent side. For the concentric knee
      extensor (K2) phase, the amputated/referent was less than the intact side. For
      the concentric work total stance phase hip, the amputated/intact was greater than
      the referent side. For the concentric hip extensor (H1) phase, the
      amputated/intact was greater than the referent side. For power TT, for the peak
      power generation stance phase knee, the amputated was less than the referent
      side. For peak power generation swing phase knee, the amputated was less than the
      referent side. For the eccentric knee flexor (K4) phase, the amputated was less
      than the intact side. For the eccentric hip flexor (H2) phase, the amputated was
      greater than the intact side. For work TF, for the concentric plantar flexor (A2)
      phase, the referent was less than the intact side. For the H1 phase, the referent
      was less than the intact side. For the H2 phase, the amputated was greater than
      the intact/referent side, and the referent was greater than the intact side. For
      power TF, for the K2 phase, the referent was less than the intact side.
      Sensitivity analysis did not alter the conclusions. CONCLUSIONS: Adaptations were
      seen in the amputated and intact legs. TT and TF use remarkably similar
      adaptation strategies at the level of the hip to compensate for the loss of
      plantar flexion power and facilitate forward progression. At the knee level,
      adaptations differed between TT and TF.

PMID- 21714958
TI  - Increased neural processing of rewarding and aversive food stimuli in recovered
      anorexia nervosa.
AB  - BACKGROUND: Recent evidence has shown that individuals with acute anorexia
      nervosa and those recovered have aberrant physiological responses to rewarding
      stimuli. We hypothesized that women recovered from anorexia nervosa would show
      aberrant neural responses to both rewarding and aversive disorder-relevant
      stimuli. METHODS: Using functional magnetic resonance imaging (fMRI), the neural
      response to the sight and flavor of chocolate, and their combination, in 15 women
      recovered from restricting-type anorexia nervosa and 16 healthy control subjects
      matched for age and body mass index was investigated. The neural response to a
      control aversive condition, consisting of the sight of moldy strawberries and a
      corresponding unpleasant taste, was also measured. Participants simultaneously
      recorded subjective ratings of "pleasantness," "intensity," and "wanting."
      RESULTS: Despite no differences between the groups in subjective ratings,
      individuals recovered from anorexia nervosa showed increased neural response to
      the pleasant chocolate taste in the ventral striatum and pleasant chocolate sight
      in the occipital cortex. The recovered participants also showed increased neural
      response to the aversive strawberry taste in the insula and putamen and to the
      aversive strawberry sight in the anterior cingulate cortex and caudate.
      CONCLUSIONS: Individuals recovered from anorexia nervosa have increased neural
      responses to both rewarding and aversive food stimuli. These findings suggest
      that even after recovery, women with anorexia nervosa have increased salience
      attribution to food stimuli. These results aid our neurobiological understanding
      and support the view that the neural response to reward may constitute a neural
      biomarker for anorexia nervosa.

PMID- 21714959
TI  - Synthesis and biological evaluation of sugar-derived chiral nitroimidazoles as
      potential antimycobacterial agents.
AB  - Chiral nitroimidazoles were synthesized using sugars as the chiral source. The
      synthesized compounds showed promising antimycobacterial property with MIC value
      in the range 6.25-12.5MUg/mL against Mycobacterium tuberculosis H(37)Rv.

PMID- 21714960
TI  - Design, synthesis, and biological evaluation of a novel class of fluorescein
      based N-glycosylamines.
AB  - A series of fluorescein-based N-glycosylamines was synthesized from the
      corresponding fluorescein amine and a partially protected d-glucose. The
      physiochemical investigation of these compounds by spectral and morphological
      studies reveals their gelation potential. The exclusive localization of
      fluorescence in the cytoplasm through cell imaging studies reveals the anti
      cancer potentials of N-glycosylamines.

PMID- 21714961
TI  - Elevated frequency of CD1c+ myeloid dendritic cells in the peripheral blood
      mononuclear cells of simian/human immunodeficiency virus (SHIV) and simian
      immunodeficiency virus (SIV) repeatedly infected Chinese rhesus macaques.
AB  - CD1c+ myeloid dendritic cells (mDCs) in the peripheral blood of 30 SHIV-SF162p4
      and SIVmac251 sequentially infected Chinese rhesus macaques were examined by flow
      cytometry to obtain further insight into mDC alterations in HIV/AIDS. The CD1c+
      cells were found to be mononuclear leukocytes rather than granulocytes, and most
      of them expressed CD20. CD1c+mDCs (CD1c+CD20-) consisted of two morphological
      subsets: the granular and the large CD1c+mDCs. The expression of HLA-DR, CD86,
      and CD11b, but no CCR7, CD83 and CD123, together with their endocytotic capacity
      indicated that they were immature mDCs. Their frequency at weeks 10 and 12 post
      infection was significantly higher than that of un-infected ones; the large
      CD1c+mDC level was significantly different between time points and almost absent
      from un-infected rhesus monkeys; significant correlations between CD1c+mDCs and
      plasma viral load levels were also observed. These data indicated a possible role
      for CD1c+mDCs in the pathophysiological process of SIV/HIV infection.

PMID- 21714962
TI  - H-2 alleles contribute to antigen 85-specific interferon-gamma responses during
      Mycobacterium tuberculosis infection.
AB  - The in vitro immune responses to mycobacterial antigens have been linked to the H
      2 loci in mice. We evaluated in vitro and in vivo immune responses during early
      Mycobacterium tuberculosis (M.tb) pulmonary infection of C57BL/6 (H-2(b)),
      C57BL/6 (H-2(k)), CBA/J (H-2(k)), and C3H/HeJ (H-2(k)) mice to determine H-2(k)
      dependent and -independent effects. H-2(k)-dependent effects included delayed and
      diminished Ag85-specific Th1 cell priming, a reduced frequency of Ag85-specific
      IFN-gamma producing cells, reduced IFN-gamma protein in vivo, and increased M.tb
      lung burden as demonstrated by C57BL/6 H-2(k) mice vs. C57BL/6 mice. H-2(k)
      independent factors controlled the amount of Ag85-specific IFN-gamma produced by
      each cell, T cell numbers, granuloma size, and lymphocytic infiltrates in the
      lungs. Overall, these results suggest that an H-2(k)-dependent suboptimal
      generation of Ag85-specific cells impairs control of early M.tb growth in the
      lungs. H-2(k)-independent factors influence the potency of IFN-gamma producing
      cells and immune cell trafficking during pulmonary M.tb infection.

PMID- 21714963
TI  - Serum levels of immunoglobulins (IgG, IgA, IgM) in Antarctic summer expeditioners
      and their relationship with seasickness.
AB  - The Antarctic continent is full of environmental extremes like isolation, cold,
      UV exposure, and blizzards etc. The present study was conducted to analyze the
      effect of ship borne journey and the impact of Antarctic harsh environment on
      serum immunoglobulin (IgG, IgM, IgA) levels and their relationship with
      seasickness in Indian expeditioners. It was observed that one month onboard ship
      journey induced an increase in serum IgA levels and decrease in IgG levels while
      after being one month off board at the Indian research station Maitri, decreased
      levels of IgG and increased levels of IgA were found. IgM levels were not altered
      in comparison to the base line control. Moreover, serum IgG level showed a
      positive correlation while IgA level showed a negative correlation with
      seasickness. The stimulation of human peripheral blood mononuclear cells (PBMCs)
      with serum of expeditioner at different places showed that IgA at lower dose
      induces the release of pro-inflammatory IL-1beta, and IL-6 cytokines from PBMCs
      while higher dose of IgA decreases proinflammatory cytokine production. The
      release of anti-inflammatory cytokines TGF-beta1 and IL-10 was not significantly
      altered. Thus, the present study concluded that ship borne journey and Antarctic
      environment lead to increased serum IgA levels while decreased IgG levels. It
      also suggests that serum IgA level could be a possible biomarker for
      environmental stress.

PMID- 21714964
TI  - Tuning the brain for music.

PMID- 21714965
TI  - Impaired recognition of musical emotions and facial expressions following
      anteromedial temporal lobe excision.
AB  - We have shown that an anteromedial temporal lobe resection can impair the
      recognition of scary music in a prior study (Gosselin et al., 2005). In other
      studies (Adolphs et al., 2001; Anderson et al., 2000), similar results have been
      obtained with fearful facial expressions. These findings suggest that scary music
      and fearful faces may be processed by common cerebral structures. To assess this
      possibility, we tested patients with unilateral anteromedial temporal excision
      and normal controls in two emotional tasks. In the task of identifying musical
      emotion, stimuli evoked either fear, peacefulness, happiness or sadness.
      Participants were asked to rate to what extent each stimulus expressed these four
      emotions on 10-point scales. The task of facial emotion included morphed stimuli
      whose expression varied from faint to more pronounced and evoked fear, happiness,
      sadness, surprise, anger or disgust. Participants were requested to select the
      appropriate label. Most patients were found to be impaired in the recognition of
      both scary music and fearful faces. Furthermore, the results in both tasks were
      correlated, suggesting a multimodal representation of fear within the amygdala.
      However, inspection of individual results showed that recognition of fearful
      faces can be preserved whereas recognition of scary music can be impaired. Such a
      dissociation found in two cases suggests that fear recognition in faces and in
      music does not necessarily involve exactly the same cerebral networks and this
      hypothesis is discussed in light of the current literature.

PMID- 21714966
TI  - Bioresorbability, porosity and mechanical strength of bone substitutes: what is
      optimal for bone regeneration?
AB  - Bone repair is a multi-dimensional process that requires osteogenic cells, an
      osteoconductive matrix, osteoinductive signalling, mechanical stability and
      vascularization. In clinical practice, bone substitute materials are being used
      for reconstructive purposes, bone stock augmentation, and bone repair. Over the
      last decade, the use of calcium phosphate (CaP) based bone substitute materials
      has increased exponentially. These bone substitute materials vary in composition,
      mechanical strength and biological mechanism of function, each having their own
      advantages and disadvantages. It is known that intrinsic material properties of
      CaP bone substitutes have a profound effect on their mechanical and biological
      behaviour and associated biodegradation. These material properties of bone
      substitutes, such as porosity, composition and geometry change the trade-off
      between mechanical and biological performance. The choice of the optimal bone
      substitutes is therefore not always an easy one, and largely depends on the
      clinical application and its associated biological and mechanical needs. Not all
      bone graft substitutes will perform the same way, and their performance in one
      clinical site may not necessarily predict their performance in another site. CaP
      bone substitutes unfortunately have yet to achieve optimal mechanical and
      biological performance and to date each material has its own trade-off between
      mechanical and biological performance. This review describes the effect of
      intrinsic material properties on biological performance, mechanical strength and
      biodegradability of CaP bone substitutes.

PMID- 21714967
TI  - Self harm is an independent predictor of mortality in trauma and burns patients
      admitted to ICU.
AB  - BACKGROUND: Patients with mental illness or depression may sustain self-inflicted
      injuries that require admission to an Intensive Care Unit (ICU). It is unknown
      whether the intent of injury leads to a greater likelihood of dying over and
      above the severity of the initial injury. Given the economic and societal burden
      of injury of self-harm, we designed this study to compare hospital outcomes of
      intentionally injured patients presenting to a tertiary ICU compared to
      unintentional injuries. METHODS: The regional trauma database was interrogated to
      produce two datasets that included all adult trauma patients admitted to the
      Alfred Intensive Care Unit between 01/07/2002 and 30/06/2007. The first included
      patients that sustained intentional injuries, the second comprised un-intentional
      injuries and acted as a control group. Logistic regression was used to model
      factors associated with mortality. RESULTS: Intentionally injured patients made
      up 4.17% of the total burns, blunt and penetrating trauma admissions to the
      Alfred ICU over the five-year study period. There was a trend towards higher
      mortality overall and in all subgroups of patients with intentional injuries when
      compared to those with un-intentional mechanisms of injury. After adjusting for
      injury severity and age, a mechanism of injury involving intentional injury was
      independently associated with a doubling of the odds of death. CONCLUSIONS: Our
      study is the first paper in the literature to describe an increased the risk of
      death within a group of patients admitted to a trauma and burns ICU following
      deliberate self-harm.

PMID- 21714968
TI  - Bioactive and osteoinductive bone graft substitutes: definitions, facts and
      myths.
AB  - The use of artificial bone grafts has been developed over recent years and is
      expected to increase further, for some indications even replacing the gold
      standard, autograft, in trauma and reconstructive surgery. However, the
      effectiveness of these materials is still a subject of debate, mostly because of
      unclear definitions or limited market surveillance. In this overview several
      facts and myths regarding bone-graft substitutes are summarized.

PMID- 21714969
TI  - Facile synthesis of hierarchical nanocrystalline ZSM-5 zeolite under mild
      conditions and its catalytic performance.
AB  - Hierarchical nanocrystalline ZSM-5 zeolite (NZ5) was synthesized at 100  degrees
      C under atmospheric pressure using methylamine as a mineralizing agent. The
      crystallization process of NZ5 was characterized by dynamic light scattering
      (DLS), X-ray diffraction (XRD), and infrared spectroscopy (FTIR). The results of
      contrastive experiments showed that evaporation of the solvent promoted the
      aggregation of primary particles, and the addition of methylamine accelerated the
      crystallization process. The NZ5 aggregate consisted of 20 nm individual
      particles, as shown in scanning electron microscope (SEM). The lattice fringes in
      the transmission electron microscope (TEM) images and the XRD results indicated
      that individual particles of NZ5 were highly crystalline. N(2) adsorption
      desorption isotherms showed that NZ5 had high BET surface areas with mesopores
      having a mean diameter of about 9 nm. NZ5 exhibited a long lifetime, a stable and
      high yield of liquid hydrocarbons, and a high anti-coking performance in methanol
      to-hydrocarbons reaction. Catalytic testing and TGA results showed that the
      lifetime of NZ5 was about ten times longer than that of micro-sized ZSM-5 zeolite
      (MZ5), and the average coking rate with NZ5 was one fifth over that of MZ5.

PMID- 21714970
TI  - Particle synergy and aerosol performance in non-aqueous liquid of two
      combinations metered dose inhalation formulations: an AFM and Raman
      investigation.
AB  - The drug-drug interaction of two pMDI (pressure metered dose inhaler) combination
      products budesonide-formoterol fumarate dihydrate and salmeterol xinafoate
      fluticasone propionate were investigated using in situ atomic force microscopy
      (AFM), equipped with a liquid cell filled with model a propellant, and Raman
      spectroscopy. Electron microscopy images of the budesonide-formoterol formulation
      suggested discrete particulates while the salmeterol-fluticasone formulation
      appeared agglomerated. Based on the analysis of the AFM curves, it is proposed
      that interactions in the budesonide-formoterol system (cohesion and adhesion) are
      dominated by van der Waals forces while interactions between salmeterol and
      fluticasone are of a chemical nature. Such observations are further substantiated
      by analysis of the Raman maps produced from pMDI actuations deposited on Andersen
      cascade impactor plates. The relevance of such synergy between particulates of
      different chemical nature is discussed. In particular, it is anticipated that
      strong interactions between particles could lead to heteroflocculation, increase
      aerosol particle size and consequently reduction of the respirable fine particle
      fraction.

PMID- 21714971
TI  - Initial experience with robotic navigation for catheter ablation of paroxysmal
      and persistent atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Remote robotic navigation (RRN) technology has been
      developed to facilitate catheter ablation of symptomatic atrial fibrillation
      (AF). Here, we assess procedural parameters of AF ablation obtained during
      initial use of RRN compared with a control group treated with a manual ablation
      approach. METHODS: Consecutive patients with symptomatic paroxysmal or persistent
      AF were subjected to radiofrequency catheter ablation with RRN (Sensei X [Hansen
      Medical, Mountain View, CA]; n = 25; mean age, 60 +/- 2.3 years) or using the
      standard manual technique (n = 61; mean age, 62 +/- 1.4 years). A circumferential
      pulmonary vein isolation approach guided by 3-dimensional electroanatomical
      mapping was followed. RESULTS: Remote robotic navigation was associated with
      reduction of overall fluoroscopy time by 26%. In a case-control subgroup analysis
      comparing 25 patients with similar clinical characteristics from each group, mean
      fluoroscopy time was reduced by 22%. Acute isolation of pulmonary veins was
      achieved in 97% (RRN) and 96% (conventional ablation), respectively. Ablation
      times and frequency of adverse events were not significantly different among
      study groups. CONCLUSIONS: The early use of RRN resulted in a significant
      reduction of overall fluoroscopy time and was equally effective and safe compared
      with manual catheter ablation.

PMID- 21714972
TI  - Oxidative stress-induced apoptosis in two patients with Alagille syndrome.
AB  - Alagille syndrome (AGS) is an autosomal dominant disorder characterized by
      cholestasis, cardiac, skeletal and ocular abnormalities. Increasing importance is
      being given to vascular and central nervous system impairment. AGS is in most
      cases caused by heterozygous mutations in the Jagged-1 (JAG1) gene encoding a
      cell-surface ligand of the Notch receptors. The interaction between Notch1 and
      JAG1 induces proliferation and inhibits apoptosis. We evaluated the role of
      apoptosis in AGS patients carrying a truncating mutation in exon 7 of JAG1.
      Peripheral blood lymphocytes (PBLs) from two patients were exposed to 2-deoxy-d
      ribose (dRib). Apoptosis was analyzed by flow cytometry, fluorescence microscopy
      and Western blotting. PBLs from patients showed a significantly higher percentage
      of apoptosis than controls both in standard culture conditions and after dRib
      treatment, however we demonstrated a lack of caspase-8 activation in those cells.
      Our results confirm that JAG1 may play a role in apoptosis regulation. In
      particular, truncating mutations in JAG1 could lead to Notch signaling inhibition
      and determine a deregulation of survival and proliferation, favoring apoptosis.
      Moreover, the lack of caspase-8 activation in AGS patients indicates a possible
      selective impairment of caspase-8 cleavage suggesting that JAG1 plays a specific
      role in the regulation of caspase-8 activation.

PMID- 21714973
TI  - Non-rapid eye movement sleep characteristics in idiopathic REM sleep behavior
      disorder.
AB  - This study investigated slow waves (SW; >75MUV and <4Hz) characteristics in
      patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).
      Thirty patients with iRBD and 30 age- and sex-matched healthy subjects underwent
      one polysomnographic (PSG) nocturnal sleep recording. SW automatic detection was
      performed on F3, C3, P3, and O1 leads and SW characteristics were derived (SW
      density, amplitude, frequency, slope, and duration of negative and positive
      phases). We also compared iRBD patients and control subjects on PSG variables and
      delta (0.25-4.0Hz) spectral power. No between-group differences were found on PSG
      variables, delta spectral power, or SW characteristics. Results show no SW
      abnormalities in iRBD patients compared to healthy participants, which suggests
      similar level of synchronization of thalamo-cortical neurons during N-REM sleep.

PMID- 21714974
TI  - Measuring ignitability for in situ burning of oil spills weathered under Arctic
      conditions: from laboratory studies to large-scale field experiments.
AB  - This paper compares the ignitability of Troll B crude oil weathered under
      simulated Arctic conditions (0%, 50% and 90% ice cover). The experiments were
      performed in different scales at SINTEF's laboratories in Trondheim, field
      research station on Svalbard and in broken ice (70-90% ice cover) in the Barents
      Sea. Samples from the weathering experiments were tested for ignitability using
      the same laboratory burning cell. The measured ignitability from the experiments
      in these different scales showed a good agreement for samples with similar
      weathering. The ice conditions clearly affected the weathering process, and 70%
      ice or more reduces the weathering and allows a longer time window for in situ
      burning. The results from the Barents Sea revealed that weathering and
      ignitability can vary within an oil slick. This field use of the burning cell
      demonstrated that it can be used as an operational tool to monitor the
      ignitability of oil spills.

PMID- 21714975
TI  - Relationship of photosynthetic carbon fixation with environmental changes in the
      Jiulong River estuary of the South China Sea, with special reference to the
      effects of solar UV radiation.
AB  - Phytoplankton cells in estuary waters usually experience drastic changes in
      chemical and physical environments due to mixing of fresh and seawaters. In order
      to see their photosynthetic performance in such dynamic waters, we measured the
      photosynthetic carbon fixation by natural phytoplankton assemblages in the
      Jiulong River estuary of the South China Sea during April 24-26 and July 24-26 of
      2008, and investigated its relationship with environmental changes in the
      presence or the absence of UV radiation. Phytoplankton biomass (Chl a) decreased
      sharply from the river-mouth to seawards (17.3-2.1 MUg L(-1)), with the dominant
      species changed from chlorophytes to diatoms. The photosynthetic rate based on
      Chl a at noon time under PAR-alone increased from 1.9 MUg C (MUg Chl a)(-1) L(-1)
      in low salinity zone (SSS<10) to 12.4 MUg C (MUg Chl a)(-1) L(-1) in turbidity
      front (SSS within 10-20), and then decreased to 2.1 MUg C (MUg Chl a)(-1) L(-1)
      in mixohaline zone (SSS>20); accordingly, the carbon fixation per volume of
      seawater increased from 12.8 to 149 MUg C L(-1) h(-1), and decreased to 14.3 MUg
      C L(-1) h(-1). Solar UVR caused the inhibition of carbon fixation in surface
      water of all the investigated zones, by 39% in turbidity area and 7-10% in
      freshwater or mixohaline zones. In the turbidity zone, higher availability of CO2
      could have enhanced the photosynthetic performance; while osmotic stress might be
      responsible for the higher sensitivity of phytoplankton assemblages to solar UV
      radiation.

PMID- 21714976
TI  - Cananginones A-I, linear acetogenins from the stem bark of Miliusa velutina
      [corrected].
AB  - Nine linear C23 and C21 acetogenins, named cananginones A-I (1-9), were isolated
      from stem bark of Miliusa velutina [corrected] . Their structures were
      established by spectroscopic methods. These compounds showed cytotoxicity against
      three cancer cell lines (KB, MCF7 and NCI-H187) with IC50 values in the range
      16.6-129.7 MUM. Only 5 showed weak antimalarial activity against Plasmodium
      falciparum. In addition, 8 and 9 exhibited weak antifungal activity against
      Candida albicans.

PMID- 21714977
TI  - Establishment of a pair of novel cloned tumour cell lines with or without
      metastatic potential from canine mammary adenocarcinoma.
AB  - We produced 23 cloned cell lines from parental CHMp, which was previously
      established from a canine mammary adenocarcinoma patient in our laboratory. Two
      representative cloned cell lines, namely, CHMp-5b and -13a, were selected and
      characterized for cellular morphology, growth potential and expression of some
      tumour-related proteins. Subsequently, we transplanted the 2 tumour cell lines
      orthotopically into female nude mice to examine their tumorigenicity and
      metastatic potential. Interestingly, despite sharing the same origin, only CHMp
      5b cells metastasized to the lung. Our results indicate that a comparison between
      these 2 cell lines at the molecular level will help us understand mechanisms of
      tumour progression, especially in the context of distant metastases originating
      from canine mammary gland tumours.

PMID- 21714978
TI  - Molecular epidemiology and genetic diversity of pneumococcal carriage among
      children in Beni State, Bolivia.
AB  - During 2007, a study of pneumococcal carriage in children was performed in two
      towns (Trinidad and Riberalta) in the Beni region of the Bolivian Amazon basin.
      Little has previously been reported regarding the epidemiology of pneumococcal
      carriage in Bolivia, and no multilocus sequence typing (MLST) of pneumococcal
      isolates from this region has previously been documented. A pneumococcal carriage
      rate of 34% was identified. Of 53 Streptococcus pneumoniae isolates that survived
      transportation for serotyping, antibiotic susceptibility testing and MLST, the
      commonest serotypes were 6A (9%), 34 (8%), 4 (6%), 9A (6%), 10A (6%), 19A (6%),
      23F (6%) and 38 (6%); overall, 26 different serotypes were identified. Antibiotic
      susceptibility testing by Etest demonstrated high levels of susceptibility to
      penicillin (93%), erythromycin (98%), vancomycin (100%), chloramphenicol (100%),
      tetracycline (96%) and trimethoprim/sulfamethoxazole (co-trimoxazole) (85%). MLST
      identified that the majority (57%) of viable isolates belonged to previously
      unrecognised sequence types that are currently unique to Bolivia.

PMID- 21714979
TI  - Investigating the spatial micro-epidemiology of diseases within a point
      prevalence sample: a field applicable method for rapid mapping of households
      using low-cost GPS-dataloggers.
AB  - Point-prevalence recording of the distribution of tropical parasitic diseases at
      village level is usually sufficient for general monitoring and surveillance.
      Whilst within-village spatial patterning of diseases exists, and can be
      important, mapping infected cases in a household-by-household setting is arduous
      and time consuming. With the development of low-cost GPS-data loggers (< L40) and
      available GoogleEarth(TM) satellite imagery, we present a field-applicable method
      based on crowdsourcing for rapid identification of infected cases (intestinal
      schistosomiasis, malaria and hookworm) by household. A total of 126 mothers with
      their 247 preschool children from Bukoba village (Mayuge District, Uganda) were
      examined with half of these mothers given a GPS-data logger to walk home with,
      returning the unit the same day for data off-loading, after which, households
      were assigned GPS coordinates. A satellite image of Bukoba was annotated with
      households denoting the infection status of each mother and child. General
      prevalence of intestinal schistosomiasis, malaria and hookworm in mothers and
      children was: 27.2 vs 7.7%, 28.6 vs 87.0% and 60.0 vs 22.3%, respectively.
      Different spatial patterns of disease could be identified likely representing the
      intrinsic differences in parasite biology and interplay with human behaviour(s)
      across this local landscape providing a better insight into reasons for disease
      micro-patterning.

PMID- 21714980
TI  - Architectures for ultrasonic planetary sample retrieval tools.
AB  - Traditional rotary corers and sample retrieval mechanisms for planetary drilling
      suffer from a variety of technical difficulties. A heavy and rigid drillstring
      must be assembled on-site and deployed with considerable applied preload and
      torque, and these mechanical loadings are difficult to react in a low gravity
      environment. Furthermore the entire drillstring must often be removed to retrieve
      samples, unless an augering approach is taken, in which case stratigraphic
      sequencing is lost. Ultrasonic tools which operate by converting an ultrasonic
      frequency to a low impacting frequency at the tool end can resolve the mechanical
      problems because they require very low applied preload and no torque to operate.
      In developing such a tool, however, several fundamental design decisions must be
      taken regarding the architecture of the transducer, horn and stack. These include
      the choice of solid or hollow transducers and the employment of single or
      multiple free-masses at the ultrasonic to low frequency conversion location. This
      paper addresses the layout of such a system by contrasting the pros and cons of
      these architectural choices and concludes that a solid system with a single free
      mass provides the best performance in the parameter range here discussed.

PMID- 21714981
TI  - Dual energy time reversed elastic wave propagation and nonlinear signal
      processing for localisation and depth-profiling of near-surface defects: a
      simulation study.
AB  - Nonlinear Elastic Wave Spectroscopy (NEWS) relies on the activation of defects by
      wave energy that propagates through the medium. In general, the response of
      activated defects will not scale linearly with the excitation amplitude, and the
      resulting nonlinear signatures can be identified and used for quality inspection.
      The efficiency of NEWS based inspection methods is therefore intrinsically linked
      to the locally deposited activation energy at the defect zone and the ability to
      generate nonlinear signatures that exceed the noise level of acquisition. Time
      Reversal techniques allow focusing of high levels of energy in small areas, and
      are consequently very useful for the local activation of defected zones. In this
      report, numerical simulations are reported showing the potential of a combination
      consisting of dual energy reciprocal Time Reversal and nonlinearity filtering
      using the Scaling Subtraction Method. The method is applied to the detection of
      planar near-surface defects parallel to the surface in a 2D domain. The results
      are evaluated for sweep excitation at different frequency ranges; for point-like
      receiver as well as extended transducers, and for in-plane as well as out-of
      plane focusing. The observable nonlinear response at the surface is linked to an
      effective nonlinearity within the medium based on the defect geometry and the
      distribution of the local stresses.

PMID- 21714982
TI  - The effect of hydraulic retention time on granular sludge biomass in treating
      textile wastewater.
AB  - The physical characteristics, microbial activities and kinetic properties of the
      granular sludge biomass were investigated under the influence of different
      hydraulic retention times (HRT) along with the performance of the system in
      removal of color and COD of synthetic textile wastewater. The study was conducted
      in a column reactor operated according to a sequential batch reactor with a
      sequence of anaerobic and aerobic reaction phases. Six stages of different HRTs
      and different anaerobic and aerobic reaction time were evaluated. It was observed
      that the increase in HRT resulted in the reduction of organic loading rate (OLR).
      This has caused a decrease in biomass concentration (MLSS), reduction in mean
      size of the granules, lowered the settling ability of the granules and reduction
      of oxygen uptake rate (OUR), overall specific biomass growth rate (ioverall),
      endogeneous decay rate (kd) and biomass yield (Yobs, Y). When the OLR was
      increased by adding carbon sources (glucose, sodium acetate and ethanol), there
      was a slight increase in the MLSS, the granules mean size, ioverall, and biomass
      yield. Under high HRT, increasing the anaerobic to aerobic reaction time ratio
      caused an increase in the concentration of MLSS, mean size of granules and
      lowered the SVI value and biomass yield. The ioverall and biomass yield increased
      with the reduction in anaerobic/aerobic time ratio. The HRT of 24 h with
      anaerobic and aerobic reaction time of 17.8 and 5.8 h respectively appear to be
      the best cycle operation of SBR. Under these conditions, not only the physical
      properties of the biogranules have improved, the highest removal of color (i.e.
      94.1+/-0.6%) and organics (i.e. 86.5+/-0.5%) of the synthetic textile dyeing
      wastewater have been achieved.

PMID- 21714983
TI  - Transformation kinetics of biochemically active compounds in low-pressure UV
      photolysis and UV/H(2)O(2) advanced oxidation processes.
AB  - Factors controlling photolysis and UV/H2O2 photooxidation rates of the
      biochemically active compounds (BACs) sulfamethoxazole, sulfamethazine,
      sulfadiazine, trimethoprim, bisphenol A, and diclofenac were determined.
      Experiments were conducted with a quasi-collimated beam apparatus equipped with
      low-pressure UV lamps. The effects of pH, H2O2 concentration, and background
      water matrix (ultrapure water, lake water, wastewater treatment plant effluent)
      on BAC transformation rates were evaluated. For the sulfa drugs, solution pH
      affected direct photolysis rates but had little effect on the hydroxyl radical
      oxidation rate. For sulfamethoxazole, the neutral form photolyzed more easily
      than the anionic form while the reverse was the case for sulfamethazine and
      sulfadiazine. For trimethoprim, the hydroxyl radical oxidation rate was higher
      for the cationic form (pH 3.6) than for the neutral form (pH 7.85). Quantum
      yields and second order rate constants describing the reaction between the
      hydroxyl radical and BACs were determined and used together with background water
      quality data to predict fluence-based BAC transformation rate constants (k'). For
      both the lake water and wastewater treatment plant effluent matrices, predicted
      k' values were generally in good agreement with experimentally determined k'
      values. At typical UV/H2O2 treatment conditions (fluence=540 mJ cm(-2), H2O2
      dose=6 mg L(-1)), BAC transformation percentages in North Carolina lake water
      ranged from 43% for trimethoprim to 98% for diclofenac. In wastewater treatment
      plant effluent, BAC transformation percentages were lower (31-97%) at the same
      treatment conditions because the hydroxyl radical scavenging rate was higher.

PMID- 21714984
TI  - Fulvic acid mediated photolysis of ibuprofen in water.
AB  - Photolysis of the non-steroidal anti-inflammatory drug ibuprofen was studied by
      exposure to a solar simulator in solutions of fulvic acid (FA) isolated from Pony
      Lake, Antarctica; Suwannee River, GA, USA; and Old Woman Creek, OH, USA. At an
      initial concentration of 10 MUM, ibuprofen degrades by direct photolysis, but the
      presence of FA significantly increases reaction rates. These reactions proceeded
      up to 6* faster in FA solutions at lower ibuprofen concentrations (0.1 MUM), but
      the rates are highly dependent upon DOM composition. Incomplete quenching of the
      reaction in the presence of isopropanol suggests that the hydroxyl radical is
      only partially responsible for ibuprofen's photodegradation in FA solutions, and
      other reactive transients likely play an important role. Liquid chromatography
      quadrupole time-of-flight mass spectrometry and NMR spectroscopy reveal the
      formation of multiple photoproducts, with three byproducts identified as 1-(4
      isobutylphenyl)ethanol, isobutylacetophenone, and a phenol derivative. Pony Lake
      FA significantly increases the production of the major byproduct relative to
      yields produced by direct photolysis and the other two FA. Thus, the photolytic
      fate of ibuprofen in sunlit waters is affected by its initial concentration and
      the source of dissolved organic matter present.

PMID- 21714985
TI  - Micellar enhanced ultrafiltration process for the treatment of olive mill
      wastewater.
AB  - Olive mill wastewater (OMW) is an important environmental pollution problem,
      especially in the Mediterranean, which is the main olive oil production region
      worldwide. Environmental impact of OMW is related to its high organic load and
      particularly to the phytotoxic and antibacterial action of its phenolic content.
      In fact, polyphenols are known as powerful antioxidants with interesting
      nutritional and pharmaceutical properties. In the present work, the efficiency of
      OMW Micellar Enhanced Ultrafiltration (MEUF) treatment for removal and
      concentration of polyphenols was investigated, using an anionic surfactant
      (Sodium Dodecyl Sulfate salt, SDS) and a hydrophobic poly(vinyldene fluoride)
      (PVDF) membrane. The effects of the process experimental conditions on the
      permeate flux were investigated, and the secondary membrane resistance created by
      SDS molecules was evaluated. The initial fluxes of OMW processing by MEUF using
      SDS were 25.7 and 44.5 l/m2 h under transmembrane pressures of 3.5 and 4.5 bar,
      respectively. The rejection rate of polyphenols without using any surfactant
      ranged from 5 to 28%, whereas, it reached 74% when SDS was used under optimum pH
      (pH 2). The MEUF provides a slightly colored permeate (about 88% less dark),
      which requires clearly less chemical oxygen demand (COD) for its oxidation (4.33%
      of the initial COD). These results showed that MEUF process can efficiently be
      applied to the treatment of OMW and for the concentration and recovery of
      polyphenols.

PMID- 21714986
TI  - Living archaeology: artefacts of specific nest site fidelity in wild chimpanzees.
AB  - Savanna chimpanzees are known to re-use areas of the landscape for sleep, and
      patterns of chimpanzee sleeping site re-use are proposed as a referential model
      for early hominin archaeological site formation. We recorded the prevalence of
      deformed but healed branches and remnants of dead branches found around fresh
      nests at the savanna site of Issa in Ugalla, Tanzania. These old nest scars were
      found in 79% of 112 beds. We also randomly selected potential nesting locations
      for a subset of 32 beds within the same trees, and found nest scars in only 19%
      of these "control" locations. We then monitored 275 nests for up to 19 months for
      decay, regeneration of new branches, and re-use. Of these 275 nest locations, 24%
      were re-used within the first nine months of monitoring, and most re-use occurred
      when the nest had already decayed and was not easily visible from the ground.
      After 18 months, the proportion of specific nest positions re-used increased to
      48%. This fidelity is likely a result of the creation of ideally-shaped support
      structures and supple new growth for mattress material with successive use of
      nest locations. We propose that specific nest site re-use may not be a direct
      product of environmental determination, but a result of "niche construction"
      through formation of good building sites within trees. Environmental modification
      through construction behaviour may have influenced both chimpanzee and early
      hominin ranging, and thus leaves behind recognisable patterns of artefact
      deposition across the landscape.

PMID- 21714987
TI  - New radiocarbon dates for the Zagros Aurignacian from Yafteh cave, Iran.

PMID- 21714988
TI  - Risk assessment of salinity and turbidity in Victoria (Australia) to stream
      insects' community structure does not always protect functional traits.
AB  - Ecological risk assessments mostly consider measures of community composition
      (structure) across large spatial scales. These assessments, using species
      sensitivity distributions (SSDs) or the relative species retention (RSR), may not
      be protective of ecosystem functions and services at smaller spatial scales. Here
      we examine how changes in biological traits, as proxy for ecosystem
      functions/services, at a fine spatial scale relate to larger scale assessment of
      structure. We use functional traits of stream insect species in south-east
      Australia in two habitats (riffle and edge/pool). We find that the protection of
      community structure in terms of 95% of species over multiple sites against
      adverse effects of salinity (as electrical conductivity) and turbidity will
      mostly, but not always, protect traits at smaller scales. Considering different
      combinations of trait modalities, contaminants and habitat, a mean of 17.5%
      (range 0%-36.8) of cases would result in under-protection of trait modalities
      despite protecting species composition (in terms of Jaccard's Index). This under
      protection of trait modalities is only because of the different spatial scales
      that community structure and the traits were considered. We recommend that where
      the protection of biological traits, ecosystem functions or ecosystem services
      from stressors is a management goal, protective targets should not be solely set
      using measures of community structure such as SSDs or RSR. To protect both
      structural and functional attributes separate risk assessments should be done.

PMID- 21714989
TI  - Accumulation of semivolatile organic compounds in Antarctic vegetation: a case
      study of polybrominated diphenyl ethers.
AB  - Antarctic plant communities are dominated by lichens and mosses which accumulate
      semivolatile organic compounds (SOCs) such as polybrominated diphenyl ethers
      (PBDEs) directly from the atmosphere. Differences in the levels of PBDEs observed
      in lichens and mosses collected at King George Island in the austral summers 2004
      05 and 2005-06 are probably explained by environmental and/or plant parameters.
      Contamination of lichens showed a positive correlation with local precipitation,
      suggesting that wet deposition processes are a major mechanism controlling the
      uptake of most PBDE congeners. These findings are in agreement with physical
      chemical data supporting that tetra- through hepta-BDEs in the Antarctic
      atmosphere are basically bound to aerosols. Conversely, accumulation of PBDEs in
      mosses appears to be controlled by other environmental factors and/or plant
      specific characteristics. Model simulations demonstrated that an ocean-atmosphere
      coupling may have played a role in the long-range transport of less volatile SOCs
      such as PBDEs to Antarctica. According to simulations, the atmosphere is the most
      important transport medium for PBDEs while the surface ocean serves as a
      temporary storage compartment, boosting the deposition/volatilization "hopping"
      effect similarly to vegetation on continents.

PMID- 21714990
TI  - Reproduction of European eel jeopardised by high levels of dioxins and dioxin
      like PCBs?
AB  - Dioxins, furans and dioxin-like polychlorinated biphenyls (PCBs) were analysed in
      muscle tissue from yellow phased European eel (Anguilla anguilla) from 38 sites
      in Belgium. Dioxin concentrations in eel vary considerably between sampling
      locations, indicating that yellow eel is a good indicator of local pollution
      levels. Measured levels of dioxin-like PCBs are much higher than those of the
      dioxins and furans. In the majority of the sites, eel has levels considered to be
      detrimental for their reproduction. Field levels of dioxin and dioxin-like PCBs
      are therefore suggested as an additional causal factor contributing to the
      decline of the European eel. 42% of the sampling sites show especially dioxin
      like PCB levels exceeding the European consumption level (with a factor 3 on
      average). Human consumption of eel, especially in these highly contaminated
      sites, seems unjustified.

PMID- 21714991
TI  - Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer.
AB  - OBJECTIVE: The CASP8 gene plays a central role in the apoptotic pathway and is
      therefore a plausible cancer susceptibility gene. However, the precise role of
      the CASP8 gene in epithelial ovarian cancer carcinogenesis is unclear. Therefore,
      we analyzed the correlation between single nucleotide polymorphisms (SNPs) and
      haplotypes in CASP8 and the risk and clinical characteristics of epithelial
      ovarian cancer (EOC) in the Chinese population. SUBJECTS AND METHODS: Eight tag
      SNPs were identified using the MassARRAY system to genotype 37 genetic
      polymorphisms around and in the CASP8 gene in 100 unrelated, healthy females.
      Then, a case-control study of 218 EOC patients and 285 controls who were matched
      on residence, age and race was conducted using these 8 tag SNPs. RESULTS: The
      risk of developing EOC was significantly decreased in association with CASP8
      rs3834129 ins>del (odds ratio (OR)(del/del)=0.129, 95% confidence interval (95%
      CI): 0.038-0.439; OR(ins/del)=0.769, 95% CI, 0.534-1.108), rs3769827 T>C
      (OR(C/C)=0.187, 95% CI: 0.070-0.500; OR(T/C)=0.729, 95% CI: 0.505-1.052),
      rs6704688 C>T (OR(T/T)=0.344, 95% CI, 0.168-0.707; OR(C/T)=0.802, 95% CI, 0.552
      1.166), and with the del-C-T haplotype of these 3 SNPs (OR=0.615, 95% CI: 0.453
      0.8363). Moreover, a notably later onset was significantly associated with the
      rs3834129 ins/del+del/del and the rs3769827 T/C+C/C genotypes (p<0.0001).
      CONCLUSIONS: Genetic variants of the CASP8 gene protect against EOC
      carcinogenesis and delay the age of EOC onset. Furthermore, these protective
      effects may be due to the dysfunctional expression of caspase-8 caused by the 
      652 6N del variant in the promoter.

PMID- 21714992
TI  - Incidence of subsequent abnormal cytology in cervical cancer patients completing
      five-years of post treatment surveillance without evidence of recurrence.
AB  - OBJECTIVE: To determine the incidence of subsequent abnormal cervical or vaginal
      cytology and confirmatory histology in women completing five-years of
      surveillance for cervical cancer without recurrence. METHODS: Following IRB
      approval, a tumor registry database identified women managed for all stages of
      cervical cancer from 1990 to 2003 who after completion of 60 months of active
      surveillance following primary therapy underwent continued vaginal or cervical
      cytologic surveillance. Retrospective review was performed to determine
      demographics, clinicopathologic variables, vaginal or cervical cytology and
      outcomes. RESULTS: Sixty-one women were identified with a median age at diagnosis
      of 41 (range 23-81). 72% of women were Caucasian, 16% were African-American with
      the remainder primarily Asian. Squamous cell carcinoma was the most common
      histology and present in 47 women (77%) with an equal proportion of women having
      G1 and G2 tumors. 80% of patients had early stage disease (Stages IA1-IIA).
      Median follow-up after completing five-years of active surveillance for all
      patients was 143 months and a total of 303 Pap tests were performed with the
      mean/median number of five cytologic evaluations per patient. A total of 17
      (5.6%) [95% CI, 3.5-8.8%] abnormal Pap tests were reported, which led to the
      performance of three diagnostic procedures. One case of moderate vaginal
      dysplasia was diagnosed and treated. CONCLUSIONS: Continued annual cytologic
      screening is of low yield in women completing five-years of surveillance that
      have remained free of recurrence. The incorporation of newer testing modalities
      including HPV testing may allow increases in the screening interval in this group
      of patients at relatively low risk for recurrence.

PMID- 21714993
TI  - Granulomatous inflammation in cartilage-hair hypoplasia: risks and benefits of
      anti-TNF-alpha mAbs.
AB  - BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive
      disorder characterized by short-limbed skeletal dysplasia. Some patients also
      have defects in cell-mediated immunity and antibody production. Granulomatous
      inflammation has been described in patients with various forms of primary
      immunodeficiencies but has not been reported in patients with CHH. OBJECTIVE: We
      sought to describe granulomatous inflammation as a novel feature in patients with
      CHH, assess associated immunodeficiency, and evaluate treatment options. METHODS:
      In a retrospective observational study we collected clinical data on 21 patients
      with CHH to identify and further characterize patients with granulomatous
      inflammation. RESULTS: Four unrelated patients with CHH (with variable degrees of
      combined immunodeficiency) had epithelioid cell granulomatous inflammation in the
      skin and visceral organs. Anti-TNF-alpha mAb therapy in 3 of these patients led
      to significant regression of granulomas. However, 1 treated patient had fatal
      progressive multifocal leukoencephalopathy caused by the JC polyomavirus. In 2
      patients immune reconstitution after allogeneic hematopoietic stem cell
      transplantation led to the complete disappearance of granulomas. CONCLUSION: To
      the best of our knowledge, this is the first report of granulomatous inflammation
      in patients with CHH. Although TNF-alpha antagonists can effectively suppress
      granulomas, the risk of severe infectious complications limits their use in
      immunodeficient patients.

PMID- 21714994
TI  - A population-based epidemiologic study of emergency department visits for
      anaphylaxis in Florida.
AB  - BACKGROUND: Previous population-based analyses of emergency department (ED)
      visits for anaphylaxis have been limited to small populations in limited
      geographic areas and focused on children or have included patients who had
      allergic conditions other than anaphylaxis. OBJECTIVE: We sought to describe the
      epidemiology and risk factors among patients with anaphylaxis presenting to
      Florida EDs. METHODS: Two thousand seven hundred fifty-one patients with
      anaphylaxis were identified for 2005-2006 within ED records by using the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM), and a validated ICD-9-CM-based algorithm. Age- and sex-specific rates
      were calculated. Regression analyses were used to determine relative risks for
      anaphylaxis caused by various triggers (food, venom, and medication) and risk
      factors (age, sex, race, and ethnicity). RESULTS: The highest observed rates were
      among the youngest male subjects (8.2/100,000 Floridians aged 0-4 years) and
      among adult female subjects (15-54 years) grouped in 10-year age categories (9.9
      10.9/100,000 Floridians). Male and black subjects were 20% and 25%, respectively,
      more likely to have a food trigger than female and white subjects. White, male,
      and older subjects were more likely to have an anaphylaxis-related ED visit
      caused by insect stings. Venom-induced anaphylaxis was more likely in August
      through October. Children were less likely than those older than 70 years
      (referent) to have medication-induced anaphylaxis (P < .03). CONCLUSION: This is
      the only ED-based population study in a US lower-latitude state. The overall rate
      is considerably lower than other US ED-based population studies. The rates of
      anaphylaxis by age group differed by sex. Male and black subjects were more
      likely to have a food trigger.

PMID- 21714995
TI  - Decreasing ED length of stay with use of the Ottawa Ankle Rules among nurses.

PMID- 21714996
TI  - ED fracture pain management in children.

PMID- 21714997
TI  - Breasts, bellies, below, and beyond: body piercing jewelry and the transfer
      technique--when in doubt, don't necessarily take it out!

PMID- 21714998
TI  - Analyses of a cantilever-beam based instrument for evaluating the development of
      polymerization stresses.
AB  - OBJECTIVE: This investigation was to generate (1) guidelines for designing a
      tensometer that satisfies the necessary accuracy and sensitivity requirements for
      measuring polymerization stress (PS), and (2) a formula for calculating PS.
      Polymerization stress remains one of the most critical properties of polymeric
      dental materials, yet methods that can accurately quantify PS have been limited
      in part due to the complexity of polymerization, and in part due to the
      instrumentation itself. METHOD: In this study, we performed analytical and finite
      element analyses on a cantilever-beam based tensometer that is used to evaluate
      shrinkage stresses during the polymerization of dental restorative composites.
      RESULTS: The PS generated by a commercial dental composite determined using our
      new tensometer agrees with the predicted trend when the beam length and/or
      specimen height is varied. SIGNIFICANCE: This work demonstrates the importance of
      beam dimension and component relative rigidity to the accuracy of PS evaluation.
      An analytical solution is also derived for the vertical beam deflection, which
      can be used for any combination of bending and shearing to properly calculate the
      PS. In addition, an easy-to-conduct calibration procedure is provided that is
      desirable for periodic tensometer recalibration.

PMID- 21715000
TI  - Arresting type 1 diabetes after diagnosis: GAD is not enough.

PMID- 21715001
TI  - Gene delivery to tumor cells by cationic polymeric nanovectors coupled to folic
      acid and the cell-penetrating peptide octaarginine.
AB  - Target ligand folic acid (FA) and cell-penetrating peptide octaarginine (R8) were
      coupled with the gene vectors (PEI(600)-CyD, PC) composed of beta-cyclodextrin
      (beta-CyD) and low-molecular-weight polyethylenimine (PEI, Mw 600) to form
      nanovectors for highly efficient gene delivery to tumor cells. The resultant
      ternary nanocomplexes of FA-PC/R8-PC/pDNA produced excellent gene transfaction
      abilities in the folate receptor (FR)-positive tumor cells in vitro and in vivo.
      The FR-mediated endocytosis and the R8-mediated transmembrane functionality
      together contributed to the high transfection levels. This study provides a
      promising means to produce gene nanovectors for in vivo applications.

PMID- 21715002
TI  - Immune responses to implants - a review of the implications for the design of
      immunomodulatory biomaterials.
AB  - A key for long-term survival and function of biomaterials is that they do not
      elicit a detrimental immune response. As biomaterials can have profound impacts
      on the host immune response the concept emerged to design biomaterials that are
      able to trigger desired immunological outcomes and thus support the healing
      process. However, engineering such biomaterials requires an in-depth
      understanding of the host inflammatory and wound healing response to implanted
      materials. One focus of this review is to outline the up-to-date knowledge on
      immune responses to biomaterials. Understanding the complex interactions of host
      response and material implants reveals the need for and also the potential of
      "immunomodulating" biomaterials. Based on this knowledge, we discuss strategies
      of triggering appropriate immune responses by functional biomaterials and
      highlight recent approaches of biomaterials that mimic the physiological
      extracellular matrix and modify cellular immune responses.

PMID- 21714999
TI  - Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients
      with recent-onset type 1 diabetes: a randomised double-blind trial.
AB  - BACKGROUND: Glutamic acid decarboxylase (GAD) is a major target of the autoimmune
      response that occurs in type 1 diabetes mellitus. In animal models of
      autoimmunity, treatment with a target antigen can modulate aggressive
      autoimmunity. We aimed to assess whether immunisation with GAD formulated with
      aluminum hydroxide (GAD-alum) would preserve insulin production in recent-onset
      type 1 diabetes. METHODS: Patients aged 3-45 years who had been diagnosed with
      type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and
      Canada, and randomly assigned to receive one of three treatments: three
      injections of 20 MUg GAD-alum, two injections of 20 MUg GAD-alum and one of alum,
      or 3 injections of alum. Injections were given subcutaneously at baseline, 4
      weeks later, and 8 weeks after the second injection. The randomisation sequence
      was computer generated at the TrialNet coordinating centre. Patients and study
      personnel were masked to treatment assignment. The primary outcome was the
      baseline-adjusted geometric mean area under the curve (AUC) of serum C-peptide
      during the first 2 h of a 4-h mixed meal tolerance test at 1 year. Secondary
      outcomes included changes in glycated haemoglobin A(1c) (HbA(1c)) and insulin
      dose, and safety. Analysis included all randomised patients with known
      measurements. This trial is registered with ClinicalTrials.gov, number
      NCT00529399. FINDINGS: 145 patients were enrolled and treated with GAD-alum
      (n=48), GAD-alum plus alum (n=49), or alum (n=48). At 1 year, the 2-h AUC of C
      peptide, adjusted for age, sex, and baseline C-peptide value, was 0.412 nmol/L
      (95% CI 0.349-0.478) in the GAD-alum group, 0.382 nmol/L (0.322-0.446) in the GAD
      alum plus alum group, and 0.413 nmol/L (0.351-0.477) in the alum group. The ratio
      of the population mean of the adjusted geometric mean 2-h AUC of C-peptide was
      0.998 (95% CI 0.779-1.22; p=0.98) for GAD-alum versus alum, and 0.926 (0.720
      1.13; p=0.50) for GAD-alum plus alum versus alum. HbA(1c), insulin use, and the
      occurrence and severity of adverse events did not differ between groups.
      INTERPRETATION: Antigen-based immunotherapy therapy with two or three doses of
      subcutaneous GAD-alum across 4-12 weeks does not alter the course of loss of
      insulin secretion during 1 year in patients with recently diagnosed type 1
      diabetes. Although antigen-based therapy is a highly desirable treatment and is
      effective in animal models, translation to human autoimmune disease remains a
      challenge. FUNDING: US National Institutes of Health.

PMID- 21715003
TI  - Irreversible optical clearing of rabbit dermis for autogenic corneal stroma
      transplantation.
AB  - Tissue engineering and transplantation of autogenic grafts have been widely
      investigated for solving problems on current allograft treatments (i.g., donor
      shortage and rejection). However, it is difficult to obtain an autogenic corneal
      stromal replacement that is composed of transparent, tough, and thick collagen
      constructs by current cell culture-based tissue engineering. Aim of this study is
      to develop transparent dermis for an autogenic corneal stroma transplantation.
      This study examined dehydration at 4-8 degrees C and carbodiimide cross-linking
      on cloudy rabbit dermis (approx. 1.8%-3.8% light transmittance at 550 nm) for
      dermis optical clearing. Transparency of dehydrated rabbit dermis was founded to
      be approx. 37.9%-41.4% at 550 nm. Additional cross-linking treatment on
      dehydrated dermis prevented from swelling and clouding in saline, and improved
      its transparency to be 56.9% at 550 nm. Rabbit corneal epithelium was found to
      regenerate on optically cleared dermis in vitro. Furthermore, no abnormal
      biological response (i.e., inflammation, vascularization, and the barrier defect
      of epithelia) or no optical functional change on optically cleared dermis was
      observed during its 4-week autogenic transplantation into rabbit corneal stromal
      pocket.

PMID- 21715004
TI  - Flow cytometric detection of BCR-ABL in cerebrospinal fluid.

PMID- 21715005
TI  - Prognostic impact of c-KIT mutations in core binding factor acute myeloid
      leukemia.
AB  - This study sought to define the prognostic impact of c-KIT mutations in core
      binding factor acute myeloid leukemia (CBF AML) patients. A total of 116 patients
      diagnosed as CBF AML in Asan Medical Center from January 1999 to May 2010 were
      enrolled in this study. We applied melting curve analyses and direct sequencing
      methods to confirm c-KIT mutations in exon 17 (mutKIT17) and exon 8 (mutKIT8). Of
      the total 116 patients, mutKIT17 were found in 36 (31%) and mutKIT8 were found in
      7 (6%). In patients with t(8;21), prognosis was significantly poorer in those
      with mutKIT17 compared to those without the mutation. This difference was limited
      to adults. In patients with inv(16), there was no prognostic impact of c-KIT
      mutations. Therefore, an analysis of mutKIT17 in adult CBF AML patients with
      t(8;21) is recommended as a means to predict prognosis.

PMID- 21715006
TI  - Treatment by Lenalidomide in lower risk myelodysplastic syndrome with 5q deletion
      -the GFM experience.
AB  - We treated 95 RBC transfusion dependent lower risk MDS with del 5q with
      Lenalidomide (10mg/day, 3 weeks/4 weeks). Median age was 70.4, median interval
      from diagnosis 29 months. IPSS was low in 31% and intermediate-1 in 69% patients.
      Del 5q was isolated, with 1 additional and >1 additional abnormality in 79%, 14%,
      and 6% patients, respectively. 62 (65%) patients achieved transfusion
      independence (TI). The only significant factor predicting TI was baseline
      platelet count >150 G/L and platelet decrease by at least 50% during the first
      weeks of treatment (p=0.001). Grade III-IV neutropenia and thrombocytopenia were
      seen in 74% and 37.9% of the cases, respectively, and 3 deaths were attributed to
      cytopenias. Eight (8%) patients developed deep venous thrombosis (DVT). Platelet
      decrease by less than 50% predicted a higher risk of DVT. Only 6 patients (6.3%)
      patients progressed to AML, but median follow-up time was short (18 months). We
      confirm the high rate of TI with Lenalidomide in lower risk MDS with del 5q. Very
      close patient monitoring for cytopenias and DVT is mandatory, especially during
      the first weeks of treatment.

PMID- 21715007
TI  - Measurement and rates of persistence with and adherence to biologics for
      rheumatoid arthritis: a systematic review.
AB  - BACKGROUND: Biologics are an important addition to the conventional care of
      patients with rheumatoid arthritis (RA). Poor persistence with and adherence to
      biologics can undermine the effectiveness of these medications. There are no
      standardized methods to track persistence with and adherence to biologics.
      OBJECTIVE: The goal of this systematic review was to assess the methods of
      measurement and reported rates of persistence with and adherence to biologic
      regimens in patients with RA in clinical practice. METHODS: Observational studies
      that evaluated persistence with and adherence to biologic treatments in patients
      with RA were identified by searching Medline and SCI-Expanded for observational
      studies published in English between January 1995 and May 2009, using the
      following search terms: adalimumab, adherence, arthritis, biologics, compliance,
      discontinuation, etanercept, infliximab, persistence, RA, treatment retention,
      and TNF. The articles were independently reviewed to identify relevant studies
      and abstracted data. RESULTS: Of the 52 studies identified, 73% were based in
      Europe and 21% were set in the United States. All but 1 study reported measures
      of persistence, such as median drug survival and rates of discontinuation and
      retention. Four studies reported on adherence, all of which were conducted in the
      United States and used administrative claims data. Methods of persistence and
      adherence measurement were unclear or, if recorded, varied considerably across
      studies. Although various continuation rates (persistence) were reported across
      studies, the overall range of continuation at 12 months was 32.0% to 90.9%.
      Continuation rates were generally higher with the addition of methotrexate or
      other disease-modifying antirheumatic drugs. CONCLUSION: The data from the
      available studies on RA treatments suggest a need for better methods for tracking
      persistence and adherence, for examining prescribing patterns, and for
      identifying interventions to improve adherence.

PMID- 21715008
TI  - A comparative analysis of the impact of a positive list system on new chemical
      entity drugs and incrementally modified drugs in South Korea.
AB  - BACKGROUND: Medical costs in South Korea have risen, in part due to increased
      demand and consumption of pharmaceutical products by an aging population and also
      because of the introduction of newer, more expensive drugs. In an effort to
      stabilize the financing of health insurance and alleviate the financial burden on
      individuals, the government implemented a policy changing the national health
      insurance drug-listing system from a negative list system to a positive list
      system (PLS). OBJECTIVES: The goal of this study was to compare differences in
      drug-listing rates for new chemical entities (NCEs) and incrementally modified
      drugs (IMDs) after South Korea introduced the PLS in December 2006. Parameters
      significantly affecting NCE and IMD listings were also identified. METHODS: New
      drug-listing data for 2007 and 2008 were obtained from the databases of the
      Health Insurance Review Agency and the Ministry of Health and Welfare.
      Descriptive analyses on the reimbursement rate and logistic regression analysis
      were conducted. Statistical significance was tested for all results, and P < 0.05
      was considered statistically significant. RESULTS: A total of 150 reimbursement
      applications (79 for NCEs, 71 for IMDs) were examined for this study. The overall
      drug-listing rate was lower than before the introduction of the PLS. Drug
      reimbursement rates for NCEs (50.6%) were lower than those for IMDs (74.6%) (P =
      0.0025). However, the price negotiation rate was 85.0% for NCEs compared with
      73.6% for IMDs (P = 0.1847). The time required for both reimbursement and drug
      pricing was significantly longer for NCE than for IMD listings (P < 0.05). Cost
      effectiveness and budget impact were 2 significant variables affecting the
      listing of NCEs. However, no significant variable was identified for IMDs.
      CONCLUSIONS: The PLS challenges the drug-listing system by decreasing the drug
      listing rate and lengthening the period for reimbursement determinations. These
      effects were more pronounced for NCE listings than for IMD listings.

PMID- 21715009
TI  - Use of patient versus population preferences in economic evaluations of health
      care interventions.

PMID- 21715010
TI  - Dietary exposure to persistent organochlorine pesticides in 2007 Chinese total
      diet study.
AB  - Dietary exposure to persistent organochlorine pesticides (OCPs) was assessed for
      Chinese populations, using the total diet study (TDS) approach in 2007.
      Multistage random cluster sampling method was used in this study. 108 composite
      samples, representative of foods "as consumed" by the Chinese were analyzed for
      residues of OCPs by a multi-residue method. The result showed that
      hexachlorobenzene (HCB), dichloro-diphenyl-trichloroethane (DDT), chlordane
      compounds (CHLs), hexachlorocyclohexane (HCH) and heptachlor could be detected
      in, respectively 84%, 39%, 37%, 13% and 5% of all samples. Concentrations of DDT
      in all samples ranged from undetectable levels to 72.2 MUg/kg. Others were minor
      components in the OCPs profile. The residual levels of OCPs were significantly
      below the Extraneous Maximum Residue Limits (EMRLs). Based on the 2000 nationwide
      food consumption survey, the average dietary exposure of the Chinese to DDT, HCH,
      HCB, CHLs, and heptachlor was estimated to be 0.016, 0.002, 0.009, 0.006, and
      0.001 MUg/kg body weight per day respectively, showing a significant decrease
      trend compared with the past. The major food groups contributing to dietary OCPs
      were aquatic foods, meats, and cereals. The average and high end estimated daily
      intakes of different OCPs for the Chinese were both lower than the tolerable
      daily intake (TDI) suggested by authorities indicating low health risk of OCPs
      dietary exposure among Chinese adults at present. However, the risk of
      carcinogenicity of the OCPs should be concerned with if the carcinogenicity
      effects from the exposures to these OCPs were considered.

PMID- 21715011
TI  - Sustained benefits from ranibizumab for macular edema following central retinal
      vein occlusion: twelve-month outcomes of a phase III study.
AB  - PURPOSE: Assess the 12-month efficacy and safety of intraocular injections of 0.3
      mg or 0.5 mg ranibizumab in patients with macular edema after central retinal
      vein occlusion (CRVO). DESIGN: Prospective, randomized, sham injection
      controlled, double-masked, multicenter clinical trial. PARTICIPANTS: We included
      392 patients with macular edema after CRVO. METHODS: Eligible patients were
      randomized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg
      of ranibizumab or sham injections. After 6 months, all patients with BCVA <=20/40
      or central subfield thickness >=250 MUm could receive ranibizumab. MAIN OUTCOME
      MEASURES: Mean change from baseline best-corrected visual acuity (BCVA) letter
      score at month 12, additional parameters of visual function, central foveal
      thickness (CFT), and other anatomic changes were assessed. RESULTS: Mean (95%
      confidence interval) change from baseline BCVA letter score at month 12 was 13.9
      (11.2-16.5) and 13.9 (11.5-16.4) in the 0.3 mg and 0.5 mg groups, respectively,
      and 7.3 (4.5-10.0) in the sham/0.5 mg group (P<0.001 for each ranibizumab group
      vs. sham/0.5 mg). The percentage of patients who gained >=15 letters from
      baseline BCVA at month 12 was 47.0% and 50.8% in the 0.3 mg and 0.5 mg groups,
      respectively, and 33.1% in the sham/0.5 mg group. On average, there was a marked
      reduction in CFT after the first as-needed injection of 0.5 mg ranibizumab in the
      sham/0.5 mg group to the level of the ranibizumab groups, which was sustained
      through month 12. No new ocular or nonocular safety events were identified.
      CONCLUSIONS: On average, treatment with ranibizumab as needed during months 6
      through 11 maintained the visual and anatomic benefits achieved by 6 monthly
      ranibizumab injections in patients with macular edema after CRVO, with low rates
      of ocular and nonocular safety events. After sham injections for 6 months,
      treatment with ranibizumab as needed for 6 months resulted in rapid reduction in
      CFT in the sham/0.5 mg group to a level similar to that in the 2 ranibizumab
      treatment groups and an improvement in BCVA, but not to the same level as that in
      the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an
      effective treatment for macular edema after CRVO. FINANCIAL DISCLOSURE(S):
      Proprietary or commercial disclosure may be found after the references.

PMID- 21715012
TI  - Selective ophthalmic arterial injection therapy for intraocular retinoblastoma:
      the long-term prognosis.
AB  - PURPOSE: To report the success rate, adverse events, and long-term prognosis of
      selective ophthalmic arterial injection (SOAI) therapy for intraocular
      retinoblastoma. DESIGN: Noncomparative case series. PARTICIPANTS: A total of 408
      eyes of 343 patients. METHODS: Retrospective chart review of patients with
      intraocular retinoblastoma treated with SOAI using a balloon catheter and
      melphalan between 1988 and 2007. MAIN OUTCOME MEASURES: The technical success
      rate of SOAI (we defined success as the successful injection of melphalan into
      the ophthalmic artery), ocular adverse events, systemic adverse events, secondary
      neoplasms, eye survival, and visual acuity. RESULTS: Selective ophthalmic
      arterial injection was successful in 1452 procedures of 1469 trials, and the
      success rate was 98.8%. Each eye received 1 to 18 rounds of SOAI. Two eyes (0.5%)
      developed severe orbital inflammation, and 2 eyes (0.5%) had diffuse
      chorioretinal atrophy. Transient periocular swelling or redness occurred in some
      cases. No severe systemic adverse events were detected. Transient bronchospasm
      occurred in 1 patient (0.3%), and transient vomiting occurred in several
      patients. Twelve secondary neoplasms occurred in 11 patients, and the cumulative
      incidence was 1.3% at 5 years, 4.8% at 10 years, and 5.8% at 15 years. The eye
      preservation rate was 100% in group A, 88% in group B, 65% in group C, 45% in
      group D, and 30% in group E according to the International Classification of
      Intraocular Retinoblastoma. Fifty-one percent of eyes had a visual acuity >0.5,
      and 36% of eyes had a visual acuity >1.0 at the last follow-up examination in
      cases without macular tumors. CONCLUSIONS: Selective ophthalmic arterial
      injection using a balloon catheter and melphalan achieved a success rate of 98.8%
      and was associated with few severe adverse events, including secondary neoplasms.
      More than half of the treated eyes were preserved, and more than half of the eyes
      without macular tumors maintained a visual acuity >0.5. Selective ophthalmic
      arterial injection is an established treatment method. We did not detect severe
      eye damage or severe systemic events; secondary neoplasms were seen but no more
      frequently than would otherwise have been expected. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 21715013
TI  - Study of possible predictors associated with self-assessed visual function after
      cataract surgery.
AB  - OBJECTIVE: To determine the preoperative or postoperative patient-related factors
      that make patients benefit more or less from cataract surgery. DESIGN:
      Multicenter, prospective, cross-sectional Swedish National Cataract Register
      study. PARTICIPANTS: A total of 14 817 patients who underwent cataract surgery
      from 2000 to 2006 in 42 Swedish ophthalmology departments. METHODS: The patients
      completed the Catquest questionnaire before and 6 months postoperatively. The 9
      questions in the revised Catquest-9SF were selected from the Catquest and recoded
      by Rasch analysis, which makes it possible to use parametric statistics when
      analyzing the study data. The change from preoperative to postoperative, the
      postoperative mean subjective visual function, and satisfaction with vision were
      assessed with multiple regression or logistic regression with dummy variables
      where appropriate, in relation to waiting time, age, preoperative and
      postoperative corrected distance visual acuity (CDVA), ocular comorbidity, a
      first- or second-eye surgery, gender, achieved postoperative refraction, correct
      sign biometry prediction error, and absolute biometry prediction error. MAIN
      OUTCOME MEASURES: Three outcome measures from Catquest-9SF of patient self
      assessed visual function after cataract surgery. RESULTS: Young age (P<0.001),
      low preoperative CDVA (P<0.001), high postoperative CDVA (P<0.001), no ocular
      comorbidity (P<0.001), and postoperative myopia (-2 to 0 diopters [D]) instead of
      hyperopia (>0 to +2 D; P<0.05) led to significantly greater improvement in
      subjective visual function and a better postoperative subjective visual function
      than the counterparts. Women (P<0.001) and patients who underwent a first-eye
      surgery (P<0.001) had greater improvement but lower postoperative subjective
      visual function (P<0.001) than men and patients who underwent a second-eye
      surgery. A correct sign biometry prediction error of plus instead of minus led to
      greater improvement in subjective visual function (P<0.01) but no difference in
      postoperative subjective visual function. The absolute biometry prediction error
      had no effect on the change in subjective visual function, the subjective mean
      visual function or satisfaction with vision. CONCLUSIONS: Several patient
      preoperative and postoperative factors are related to the self-assessed benefit
      of cataract surgery. Age, preoperative and postoperative CDVAs, ocular
      comorbidity, a first- or second-eye surgery, gender, and achieved postoperative
      refraction were related to changes in subjective visual function, subjective
      visual function, and satisfaction with vision.

PMID- 21715014
TI  - No association between affective and behavioral dysregulation and parameters of
      thyroid function in youths.
AB  - OBJECTIVE: Evidence from adults suggests that changes in thyroid function are
      associated with the development of bipolar disorder (BD) and severe mood
      dysregulation. A dysregulation profile based on the Child Behavior Checklist
      (CBCL-DP) describes a phenotype with severe mood problems in youth. The present
      study investigated whether altered thyroid functioning in youths is associated
      with the severe mood dysregulation symptoms characterized by the CBCL-DP.
      METHODS: We analyzed the thyroid function data from 262 children and adolescents
      (n = 262 for serum TSH, n = 148 for free triiodothyronine [fT3] and n = 153 for
      free thyroxine [fT4]) with their CBCL-DP composite score. We created and compared
      high CBCL-DP and low CBCL-DP subgroups with regard to their serum TSH, fT3 and
      fT4 concentrations as well as the presence or absence of subclinical
      hypothyroidism. RESULTS: We did not detect between-group differences in serum
      TSH, fT3 and fT4 concentrations, nor were there significant correlations between
      youths' CBCL-DP scores and their serum TSH, fT3 and fT4 concentrations for either
      the whole sample or any subgroup. Post-hoc power analyses indicated that adequate
      to moderate power existed to detect between-group differences in fT3 and fT4
      concentrations, respectively, but that larger TSH samples would be required to
      detect the same differences in those concentrations. LIMITATIONS: This study had
      a retrospective design, fewer females than males, and reduced power with respect
      to TSH concentrations. CONCLUSIONS: The present investigation does not support
      the association between elevated serum-TSH concentrations and severe mood
      dysregulation in youths. However, these findings should be confirmed in future
      large-scale studies.

PMID- 21715015
TI  - Identification of anti-syntaxin 5 autoantibody as a novel serum marker of
      endometriosis.
AB  - The sensitivity and specificity of CA125, as a sole serum marker of
      endometriosis, are not high enough for routine clinical assessment. To explore
      new markers for the diagnosis of endometriosis, serum autoantibodies in
      endometriotic patients were investigated employing a fibroblast cell line, two
      dimensional (2D) gel electrophoresis and Western blotting. Proteins reacting with
      serum autoantibodies by Western blotting were identified using MASCOT analysis.
      ELISAs were then prepared using recombinant proteins and titers of serum
      autoantibodies were determined in the endometriotic patients, disease controls,
      and healthy subjects. Among the autoantibodies identified, anti-syntaxin 5 (STX5)
      autoantibody levels were significantly elevated in endometriotic patients.
      Sensitivity (53.6%) and accuracy (72.2%) of the serum anti-STX5 autoantibody
      assay were better than those of serum CA125 levels (36.2% and 62.9%,
      respectively) for diagnosis. The sensitivity of anti-STX5 autoantibody was
      remarkably high in Stage II (80.0%) compared with that of CA125 (40.0%). A
      combination assay of anti-STX5 autoantibody with CA125 improved the overall
      sensitivity to 69.6%. We conclude that serum anti-STX5 autoantibody, which was
      discovered by a proteomic approach, is a potential new serum marker for the
      diagnosis of endometriosis. This initial study now requires validation by further
      clinical evaluation.

PMID- 21715016
TI  - Selective decision-making deficits in at-risk gamblers.
AB  - Despite reasonable knowledge of pathological gambling (PG), little is known of
      its cognitive antecedents. We evaluated decision-making and impulsivity
      characteristics in people at risk of developing PG using neuropsychological
      tests. Non-treatment seeking volunteers (18-29 years) who gamble >= 5 times/year
      were recruited from the general community, and split into two groups: those "at
      risk" of developing PG (n=74) and those social, non-problem gamblers (n=112).
      Participants undertook the Cambridge Gamble and Stop-signal tasks and were
      assessed with the Mini-International Neuropsychiatric Interview and the Yale
      Brown Obsessive Compulsive Scale Modified for Pathological Gambling. On the
      Cambridge Gamble task, the at-risk subjects gambled more points overall, were
      more likely to go bankrupt, and made more irrational decisions under situations
      of relative risk ambiguity. On the Stop-signal task, at-risk gamblers did not
      differ from the social, non-problem gamblers in terms of motor impulse control
      (stop-signal reaction times). Findings suggest that selective cognitive
      dysfunction may already be present in terms of decision-making in at-risk
      gamblers, even before psychopathology arises. These findings implicate selective
      decision-making deficits and dysfunction of orbitofronto-limbic circuitry in the
      chain of pathogenesis between social, non-problematic and pathological gambling.

PMID- 21715017
TI  - Examining a progressive model of self-stigma and its impact on people with
      serious mental illness.
AB  - The self-esteem of some people with serious psychiatric disorders may be hurt by
      internalizing stereotypes about mental illness. A progressive model of self
      stigma yields four stages leading to diminished self-esteem and hope: being aware
      of associated stereotypes, agreeing with them, applying the stereotypes to one's
      self, and suffering lower self-esteem. We expect to find associations between
      proximal stages - awareness and agreement - to be greater than between more
      distal stages: awareness and harm. The model was tested on 85 people with
      schizophrenia or other serious mental illnesses who completed measures
      representing the four stages of self-stigma, another independently-developed
      instrument representing self-stigma, proxies of harm (lowered self-esteem and
      hopelessness), and depression. These measures were also repeated at 6-month
      follow-up. Results were mixed but some evidence supported the progressive nature
      of self-stigma. Most importantly, separate stages of the progressive model were
      significantly associated with lowered self-esteem and hope. Implications of the
      model for stigma change are discussed.

PMID- 21715018
TI  - Retroviral restriction and dependency factors in primates and carnivores.
AB  - Recent studies have extended the rapidly developing retroviral restriction factor
      field to cells of carnivore species. Carnivoran genomes, and the domestic cat
      genome in particular, are revealing intriguing properties vis-a-vis the primate
      and feline lentiviruses, not only with respect to their repertoires of virus
      blocking restriction factors but also replication-enabling dependency factors.
      Therapeutic application of restriction factors is envisioned for human
      immunodeficiency virus (HIV) disease and the feline immunodeficiency virus (FIV)
      model has promise for testing important hypotheses at the basic and translational
      level. Feline cell-tropic HIV-1 clones have also been generated by a strategy of
      restriction factor evasion. We review progress in this area in the context of
      what is known about retroviral restriction factors such as TRIM5alpha, TRIMCyp,
      APOBEC3 proteins and BST-2/Tetherin.

PMID- 21715019
TI  - Strain-specific viral distribution and neuropathology of feline immunodeficiency
      virus.
AB  - Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of
      domestic cats, and is the causative agent of feline AIDS. Similar to human
      immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of
      lymphocytes and macrophages, and results in chronic progressive immune system
      collapse and death. Neuropathologic correlates of FIV infection have not yet been
      elucidated, and may be relevant to understanding HIV-associated neurologic
      disease (neuroAIDS). As in HIV, FIV strains have been shown to express
      differential tendencies towards development of clinical neuroAIDS. To interrogate
      viral genetic determinants that might contribute to neuropathogenicity, cats were
      exposed to two well-characterized FIV strains with divergent clinical phenotypes
      and a chimeric strain as follows: FIV(PPR) (PPR, relatively apathogenic but
      associated with neurologic manifestations), FIV(C36) (C36, immunopathogenic but
      without associated neurologic disease), and Pcenv (a chimeric virus consisting of
      a PPR backbone with substituted C36 env region). A sham inoculum control group
      was also included. Peripheral nerve conduction velocity, CNS imaging studies,
      viral loads and hematologic analysis were performed over a 12 month period. At
      termination of the study (350 days post-inoculation), brain sections were
      obtained from four anatomic locations known to be involved in human and primate
      lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven
      markers of inflammation revealed that Pcenv infection resulted in mild
      inflammation of the CNS, microglial activation, neuronal degeneration and
      apoptosis, while C36 and PPR strains induced minimal neuropathologic changes.
      Conduction velocity aberrations were noted peripherally in all three groups at 63
      weeks post-infection. Pcenv viral load in this study was intermediate to the
      parental strains (C36 demonstrating the highest viral load and PPR the lowest).
      These results collectively suggest that (i) 3' C36 genomic elements contribute to
      viral replication characteristics, and (ii) 5' PPR genomic elements contribute to
      CNS manifestations. This study illustrates the potential for FIV to provide
      valuable information about neuroAIDS pathogenesis related to genotype and viral
      kinetics, as well as to identify strains useful to evaluation of therapeutic
      intervention.

PMID- 21715021
TI  - Novel antigens for detection of cell mediated immune responses to Mycobacterium
      avium subsp. paratuberculosis infection in cattle.
AB  - Paratuberculosis is a chronic infection of the intestine of ruminants caused by
      Mycobacterium avium subsp. paratuberculosis (MAP). Early stage MAP infection can
      be detected by measuring specific cell mediated immune responses, using the whole
      blood interferon-gamma (IFN-gamma) assay. Available IFN-gamma assays use purified
      protein derivative of MAP (PPDj) which are complex antigen mixtures with low
      specificity. The objectives of this study were to evaluate immunogenicity and
      specificity of 14 novel recombinant antigens for use in the IFN-gamma assay and
      to assess the consistency of IFN-gamma responses. The study included blood
      samples from 26 heifers from a MAP infected herd, collected three times with four
      to five-week intervals, and blood samples from 60 heifers of a non-infected herd
      collected once. Heifers of the non-infected herd were used to establish cut-off
      values for each antigen. The case definition was an animal with >= 2 positive
      tests for >= 4 antigens, resulting in 13 cases and 13 non-cases. IFN-gamma levels
      of cases were higher compared to IFN-gamma levels of non-cases (P<0.05). The
      results of the IFN-gamma assay using PPDj did not correlate well with the results
      using the novel antigens. PPDj produced elevated IFN-gamma responses of samples
      from both the non-infected and the MAP infected herd, indicating unspecific IFN
      gamma responses and showed low consistency. Three latency proteins, LATP-1, LATP
      2 and LATP-3 gave positive IFN-gamma tests that correlated very well with the
      case definition suggesting high immunogenicity. Three tested antigens, LATP-2,
      MAP-1 and MAP-2 have no homologue in the M. avium subsp. avium or M. bovis genome
      and could be promising diagnostic antigens, especially LATP-2 correlated highly
      with the case definition.

PMID- 21715020
TI  - The role of BST2/tetherin in feline retrovirus infection.
AB  - Pathogenic retroviral infections of mammals have induced the evolution of
      cellular anti-viral restriction factors and have shaped their biological
      activities. This intrinsic immunity plays an important role in controlling viral
      replication and imposes a barrier to viral cross-species transmission. Well
      studied examples of such host restriction factors are TRIM5alpha, an E3 ubiquitin
      ligase that binds incoming retroviral capsids in the cytoplasm via its C-terminal
      PRY/SPRY (B30.2) domain and targets them for proteasomal degradation, and APOBEC3
      proteins, cytidine deaminases that induce hypermutation and impair viral reverse
      transcription. Tetherin (BST-2, CD317) is an interferon-inducible transmembrane
      protein that potently inhibits the release of nascent retrovirus particles in
      single-cycle replication assays. However, whether the primary biological activity
      of tetherin in vivo is that of a restriction factor remains uncertain as recent
      studies on human tetherin suggest that it is unable to prevent spreading
      infection of human immunodeficiency virus type 1 (HIV-1). The feline tetherin
      homologue resembles human tetherin in amino acid sequence, protein topology and
      anti-viral activity. Transiently expressed feline tetherin displays potent
      inhibition of feline immunodeficiency virus (FIV) and HIV-1 particle release.
      However, stable ectopic expression of feline tetherin in a range of feline cell
      lines has no inhibitory effect on the growth of either primary or cell culture
      adapted strains of FIV. By comparing and contrasting the activities of the felid
      and primate tetherins against their respective immunodeficiency-causing
      lentiviruses we may gain insight into the contribution of tetherins to the
      control of lentiviral replication and the evolution of lentiviral virulence.

PMID- 21715022
TI  - Are endogenous feline leukemia viruses really endogenous?
AB  - Full length endogenous feline leukemia virus (FeLV) proviruses exist within the
      genomes of many breeds of domestic cat raising the possibility that they may also
      exist in a transmissible exogenous form. Such viruses would share receptor usage
      with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by
      recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV.
      Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV
      A, consistent with their recombinatorial origin. In order to assess whether
      endogenous viruses are transmitted between cats, we examined primary isolates of
      FeLV for which the viral subgroup had been determined for the presence of a
      subgroup B virus that lacked an FeLV-A. Here we describe the identification of
      two primary field isolates of FeLV (2518 and 4314) that appeared to contain
      subgroup B virus only by classical interference assays, raising the possibility
      of between-host transmission of endogenous FeLV. Sequencing of the env gene and
      U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes
      contained endogenous viral env genes. However the viral 3' LTRs appeared
      exogenous in origin with a putative 3' recombination breakpoint residing at the
      3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a
      truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A)
      whilst no helper subgroup A viral genome was detected in virions of FeLV-4314.
      The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have
      allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was
      presumably present during first infection. Given time, a similar evolution may
      also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be
      mobilised by acquisition of exogenous LTRs yielding novel viruses that type
      biologically as FeLV-B.

PMID- 21715023
TI  - Methods for assessing feline immunodeficiency virus infection, infectivity and
      purification.
AB  - Infection of cats with the feline immunodeficiency virus (FIV) recapitulates many
      aspects of infection of humans with HIV, including highly activated but
      ineffectual immune responses. Infected hosts remain seropositive for life, and
      detection of antibodies is the mainstay of diagnosis. However, to quantify virus
      for research or prognosis, viral proteins, nucleic acids or enzymes, are
      typically measured by ELISA, PCR or activity, respectively. While such assays are
      in wide use, they do not distinguish whole, infectious viral particles from
      defective or disrupted viruses. Titers of infectious viral particles may be
      estimated from tissue culture infectious doses or by enumerating cell-associated
      viral proteins, viral transcriptional activity or formation of syncytia. To
      analyze the viral proteome and the incorporation of host components into viral
      envelopes, pure lentiviral preparations are required. Methods for purifying
      lentiviruses include ultracentrifugation to separate particles by size, mass
      and/or density; chromatography to separate particles by charge, affinity or size;
      and additional removal of extraviral proteins and exosomes through subtilisin
      digestion or immunoaffinity. This article reviews advantages and disadvantages of
      different approaches to purification of lentiviruses with special reference to
      suitability for FIV, and highlights effects of purification on immune responses
      and immune assays.

PMID- 21715024
TI  - Identifying innate immune pathways of the chicken may lead to new antiviral
      therapies.
AB  - Zoonotic viruses, such as highly pathogenic avian influenza (HPAI), present a
      significant threat to both the poultry industry and public health. The present
      method of controlling avian influenza (AI) relies on good farming practice with
      limited use of vaccination in some countries. However, new ways to control
      disease outbreaks might be possible with additional knowledge of the natural host
      response to virus. Moreover, manipulation of the innate immune system in mammals
      improves the outcomes following viral infection. A similar approach might be
      applied to the chicken, nevertheless, a greater knowledge of the chicken innate
      immune system is required. This review outlines important mammalian antiviral
      mechanisms that have been modulated to strengthen viral immunity and highlights
      the potential application of these strategies in the chicken, especially in
      regards, to AI.

PMID- 21715025
TI  - Primate and feline lentiviruses in current intrinsic immunity research: the cat
      is back.
AB  - Retroviral restriction factor research is explaining long-standing lentiviral
      mysteries. Asking why a particular retrovirus cannot complete a critical part of
      its life cycle in cells of a particular species has been the starting point for
      numerous discoveries, including heretofore elusive functions of HIV-1 accessory
      genes. The potential for therapeutic application is substantial. Analyzing the
      feline immunodeficiency virus (FIV) life cycle has been instrumental and the
      source of some surprising observations in this field. FIV is restricted in cells
      of various primates by several restriction factors including APOBEC3 proteins
      and, uniquely, TRIM proteins from both Old and New World monkeys. In contrast,
      the feline genome does not encode functional TRIM5alpha or TRIMCyp proteins and
      HIV-1 is primarily blocked in feline cells by APOBEC3 proteins. These can be
      overcome by inserting FIV vif or even SIVmac vif into HIV-1. The domestic cat and
      its lentivirus are positioned to offer strategic research opportunities as the
      field moves forward.

PMID- 21715026
TI  - Comparison of a classical Th1 bacteria versus a Th17 bacteria as adjuvant in the
      induction of experimental autoimmune encephalomyelitis.
AB  - The relative contribution of myelin-specific Th1 and Th17 cells in the pathology
      of multiple sclerosis (MS) and its animal model, experimental autoimmune
      encephalomyelitis (EAE), is controversial. IL-12, the key cytokine necessary for
      the differentiation of Th1 cells, has been found to be dispensable for EAE
      induction; while the related cytokine associated with Th17 cells, IL-23, is a
      critical factor for inducing EAE. Since EAE is induced by immunization with
      myelin proteins in CFA which contains M. tuberculosis that generates a
      prototypical Th1-mediated immune response, we sought to determine if replacing
      the M. tuberculosis in the adjuvant with a bacterium that induces an IL-23
      dependent Th17 cell response during infection would induce EAE with a different
      phenotype. C. rodentium, a bacterium that requires IL-23 for protective immunity,
      was used as the adjuvant in EAE and compared to CFA. Mice immunized with C.
      rodentium adjuvant (CRA) developed classical signs of EAE, similar to CFA
      immunized mice, but disease was less severe with a later onset and slower
      progression than CFA. Surprisingly, the peripheral cytokine profile revealed
      similar numbers of Th1 and Th17 cells for both CFA and CRA-immunized mice;
      however, the number of Th1 and Th17 cells was significantly reduced in the CNS of
      CRA-immunized mice. The development of EAE in CRA-immunized mice was associated
      with epitope spreading. The unique clinical course of CRA immunizations helps
      serve as a useful alternative model for studying EAE pathogenesis and potential
      therapeutics for MS.

PMID- 21715027
TI  - Microbiological profile with antibiotic sensitivity pattern of cholesteatomatous
      chronic suppurative otitis media among children.
AB  - INTRODUCTION: Chronic suppurative otitis media (CSOM) is the most common cause of
      childhood hearing impairment in the developing countries and atticoantral type is
      associated with increased incidence of intracranial and extracranial
      complications. This study was undertaken to define the microbiology of
      atticoantral type of chronic otitis media and the antibiotic sensitivity pattern,
      thereby reducing the potential risks of complications. MATERIALS AND METHODS: A
      retrospective study was done in the Department of Otolaryngology, JIPMER,
      Puducherry from the year August 2003 to October 2009 using the medical record
      department database to retrieve the patient details. During this study period,
      223 children with atticoantral type CSOM consisting of 126 males and 97 females
      with an age range of 1-14 years were assessed. Patients with persistent otorrhea
      for more than 3 months with atticoantral type of chronic otitis media were
      selected. The exudates were collected under sterile conditions and inoculated
      onto culture media; bacterial growth and antibiotic sensitivity pattern were
      studied. RESULTS: Nine species of micro organisms were isolated from the middle
      ear aspirate, Pseudomonas aeruginosa being the most predominant isolate
      constituting about 32% (72 discharging ears) of the total isolates followed by
      Proteus mirabilis (20% of isolates) and Staphylococcus aureus (19% of isolates).
      Gram negative organisms accounted 58% of total isolates and gram positive
      organisms constituted 22% isolates. Candida albicans and methicillin resistant S.
      aureus were identified in 4% and 2% of isolates, respectively. 100% of
      Pseudomonas isolates showed susceptibility to ceftazidime and a high sensitivity
      (92% of isolates) to ciprofloxacin and 88% isolates were sensitive to amikacin.
      100% of P. mirabilis isolated from inoculates showed sensitivity to ceftazidime
      and ciprofloxacin. It also showed 87-97% sensitivity to ceftriaxone, amikacin and
      ampicillin. All (100%) of the Staphylococcus isolates were sensitive to
      vancomycin and 84-86% were sensitive to ciprofloxacin and erythromycin. In
      general, gram negative organisms showed increased sensitivity to ceftazidime,
      ciprofloxacin and amikacin, while gram positive organisms to vancomycin,
      erythromycin and ciprofoxacin. CONCLUSION: Continuous and periodic evaluation of
      microbiological pattern and antibiotic sensitivity of cholesteatomatous CSOM is
      necessary to decrease the potential risks of complications by early institution
      of appropriate systemic and topical antibiotic alongside mastoid exploration. We
      believe that our data may contribute to an effective medical management of
      chronic suppurative otitis media with cholesteatoma. Since the most common
      organisms in our clinical set up being P. aeruginosa, P. mirabilis and S. aureus,
      which showed a percentage susceptibility of 100% to ceftazidime and vancomycin,
      thus making it an empirical antibiotic combination therapy of choice in the
      recent times.

PMID- 21715028
TI  - Asymmetry of GPCR oligomers supports their functional relevance.
AB  - G protein-coupled receptors (GPCRs) can exist as dimers or as larger oligomeric
      clusters that enable intercommunication between different receptor protomers
      within the same complex. This phenomenon is observed at three distinct levels:
      (i) at the level of ligand binding where the activation of one protomer can
      allosterically inhibit or facilitate ligand binding to the second protomer; (ii)
      at the level of ligand-induced conformational switches, which occur between
      transmembrane domains of the two protomers; and (iii) within GPCR-associated
      protein complexes, either directly at the level of GPCR-interacting proteins or
      at further downstream levels of the complex. Intercommunication at these
      different levels introduces asymmetry within GPCR dimers wherein each protomer
      fulfills its specific task. In this review, we discuss how the asymmetric
      behavior of GPCRs highlights the advantage of oligomeric receptor organization
      and supports the functional relevance of GPCR dimerization.

PMID- 21715029
TI  - Non-invasive assessment of acute vascular inflammation after PCI using USPIO
      enhanced MRI in vivo.

PMID- 21715030
TI  - Management of cardiac myxoma during pregnancy: a case series and review of the
      literature.
AB  - Cardiac myxomas are the most common primary benign tumors of the heart. The
      reported incidence during pregnancy is extremely low with only 17 reported cases
      in the medical literature. Standard therapy involves surgical resection given the
      potential for embolization. In the pregnant patient, however, the risks of
      embolization must be balanced against the risk of cardiopulmonary bypass to the
      mother and the fetus. We present two cases of cardiac myxoma diagnosed during
      pregnancy and review the presentation and management strategies of previously
      reported cases. In conclusion, successful surgical resection of the myxomas
      during pregnancy was performed in both of our cases. Given the rarity of cases,
      individual multidisciplinary assessment and management strategies are essential.

PMID- 21715031
TI  - Peak oxygen uptake correlates with disease severity and predicts outcome in adult
      patients with Ebstein's anomaly of the tricuspid valve.
AB  - BACKGROUND: Ebstein's anomaly of the tricuspid valve often results in
      biventricular dysfunction and functional deterioration. Little is known about the
      relation between exercise capacity, disease severity and outcome in adults with
      Ebstein's anomaly. METHODS: Data on all patients with Ebstein's anomaly of the
      tricuspid valve who underwent cardiopulmonary exercise testing in our tertiary
      center were collected. The relation between exercise parameters, anatomic
      severity (Glasgow outcome score) and the combined end-point of death, non
      elective hospitalization and surgical repair was studied using Cox regression
      analysis. RESULTS: A total of 51 adult patients fulfilled inclusion criteria (49%
      male, mean age 37.8+/-13.6 years). Mean peak oxygen uptake (peak VO2) was 63.2+/
      18.7% of predicted, the slope of ventilation per unit of carbon dioxide output
      (VE/VCO2 slope) 37.4+/-11.4, heart rate reserve (HRR) 23.6+/-22.7 bpm. A
      significantly lower peak VO2 was found in patients with a higher Glasgow outcome
      score, higher cardiothoracic ratio and documented atrial shunt. Peak VO2 (HR for
      value <60% of predicted 3.47, 95% CI: 1.28-9.44, p=0.015) and HRR (HR for value
      <25 bpm 3.07, 95% CI: 1.24-7.61, p=0.016) were significant predictors of outcome,
      the former being the strongest on multivariable analysis. CONCLUSIONS: Reduced
      exercise capacity in patients with Ebstein's anomaly relates to severity of the
      underlyingdisease and is a strong and independent predictor of outcome.
      Cardiopulmonary exercise testing should be incorporated in the follow-up and risk
      stratification of patients with this relatively uncommon and challenging cardiac
      defect.

PMID- 21715032
TI  - Diagnostic and epidemiologic analysis of the 2008-2010 investigation of a multi
      year outbreak of contagious equine metritis in the United States.
AB  - Contagious equine metritis (CEM) is a highly contagious venereal disease of
      horses caused by Taylorella equigenitalis. During testing for semen export
      purposes, a stallion in Kentucky was found to be T. equigenitalis culture
      positive in December of 2008. This finding triggered an extensive regulatory
      investigation to search for additional positive horses, determine the extent of
      the outbreak, identify the potential source of the outbreak, and ultimately
      return the United States to CEM-free status. The investigation included over 1000
      horses located in 48 states. Diagnostic testing found a total of 22 stallions, 1
      gelding and 5 mares culture positive for T. equigenitalis. Epidemiologic analysis
      indicated that all of the positive horses were linked to a single common source,
      most likely a Fjord stallion imported into the United States in 2000. The T.
      equigenitalis strain subsequently spread to other stallions via undetermined
      indirect mechanisms at shared breeding facilities, and to mares via artificial
      insemination and live breeding. This CEM outbreak and investigation represent the
      largest ever in the United States based on the number of exposed horses tested
      and their geographic distribution.

PMID- 21715033
TI  - The causal relationship between education, health and health related behaviour:
      evidence from a natural experiment in England.
AB  - I exploit exogenous variation in the likelihood to obtain any sort of educational
      qualification between January- and February-born individuals for 13 academic
      cohorts in England. For these cohorts compulsory schooling laws interacted with
      the timing of the CSE and O-level exams to change the probability of obtaining a
      qualification by around 2-3 percentage points. I then use data on individuals
      born in these two months from the British Labour Force Survey and the Health
      Survey for England to investigate the effects of education on health using being
      February-born as an instrument for education. The results indicate neither an
      effect of education on various health related measures nor an effect on health
      related behaviour, e.g., smoking, drinking or eating various types of food.

PMID- 21715034
TI  - Conjugal bereavement effects on health and mortality at advanced ages.
AB  - Spousal bereavement at old ages may lead to dramatic changes in health. This
      paper investigates whether spousal bereavement has a causal effect on health and
      on mortality of the surviving spouse. We advance on the literature in two main
      ways. First, we model survivals of both spouses and the dynamic evolution of
      health jointly, allowing for potential endogeneity of timing of bereavement and
      health in explaining mortality of the surviving spouse. Second, we use a flexible
      non-parametric data dimensionality reduction method to thoroughly characterize
      health (using 22 health indicators) by a limited number of latent health
      indicators. This allows us to investigate the causal effect of spousal
      bereavement on mortality and on all aspects of health simultaneously. Our
      analyses are based on an ongoing longitudinal survey that follows a random sample
      of older individuals from 1992. We find strong instantaneous effects of
      bereavement on mortality and on certain aspects of health. Individuals lose on
      average 12% of residual life expectancy after conjugal bereavement. Conjugal
      bereavement affects the share of healthy years in residual lifetime, primarily
      because healthy years are replaced by years with chronic diseases. The strong
      direct effects of bereavement suggest that monitoring and/or interventions just
      after spousal bereavement are important for the length and quality of life of
      older bereaved individuals.

PMID- 21715035
TI  - Effectiveness of state-level vaccination mandates: evidence from the varicella
      vaccine.
AB  - This paper utilizes longitudinal data on varicella (chickenpox) immunizations in
      order to estimate the causal effects of state-level school-entry and daycare
      entry immunization mandates within the United States. We find significant causal
      effects of mandates upon vaccination rates among preschool children aged 19-35
      months; these effects appear in the year of mandate adoption, peak two years
      after adoption, and show a minimal difference from the aggregate trend about six
      years after adoption. For a mandate enacted in 2000, the model and estimates
      imply that roughly 20% of the short-run increase in state-level immunization
      rates was caused by the mandate introduction. We find no evidence of differential
      effects for different socioeconomic groups. Combined with previous cost-benefit
      analyses of the varicella vaccine, the estimates suggest that state-level
      mandates have been effective from an economic standpoint.

PMID- 21715036
TI  - Putting different price tags on the same health condition: re-evaluating the well
      being valuation approach.
AB  - Many recent writings in health policy have proposed that health be valued
      directly and in monetary terms using the new well-being valuation method. Yet
      there is no clear consensus on what the best measure of individual's experience
      may be for the evaluation process. To shed light on this issue, monetary values
      for a number of health problems are compared across different well-being measures
      within the same UK data set. We find that, whilst there is strong internal
      consistency of health impacts within each well-being measure, hugely different
      monetary valuations are obtained for the same health problem across different
      well-being measures. Our results, although should only viewed as illustrative,
      call for economists to rethink about which measure of well-being or experienced
      utility to be used in the well-being valuation method, should the approach ever
      be implemented in real policy contexts.

PMID- 21715037
TI  - AMPK regulates metabolism and survival in response to ionizing radiation.
AB  - BACKGROUND AND PURPOSE: AMPK is a metabolic sensor and an upstream inhibitor of
      mTOR activity. AMPK is phosphorylated by ionizing radiation (IR) in an ATM
      dependent manner, but the cellular consequences of this phosphorylation event
      have remained unclear. The objective of this study was to assess whether AMPK
      plays a functional role in regulating cellular responses to IR. METHODS: The
      importance of AMPK expression for radiation responses was investigated using both
      MEFs (mouse embryo fibroblasts) double knockout for AMPK alpha1/alpha2 subunits
      and human colorectal carcinoma cells (HCT 116) with AMPK alpha1/alpha2 shRNA
      mediated knockdown. RESULTS: We demonstrate here that IR results in
      phosphorylation of both AMPK and its substrate, ACC. IR moderately stimulated
      mTOR activity, and this was substantially exacerbated in the absence of AMPK.
      AMPK was required for IR induced expression of the mTOR inhibitor REDD1,
      indicating that AMPK restrains mTOR activity through multiple mechanisms.
      Likewise, cellular metabolism was deregulated following irradiation in the
      absence of AMPK, as evidenced by a substantial increase in oxygen consumption
      rates and lactate production. AMPK deficient cells showed impairment of the G1/S
      cell cycle checkpoint, and were unable to support long-term proliferation during
      starvation following radiation. Lastly, we show that AMPK proficiency is
      important for clonogenic survival after radiation during starvation. CONCLUSIONS:
      These data reveal novel functional roles for AMPK in regulating mTOR signaling,
      cell cycle, survival and metabolic responses to IR.

PMID- 21715038
TI  - Elevated alanine aminotransferase is associated with metabolic syndrome but not
      consistently associated with impaired fasting glucose or type 2 diabetes
      mellitus.
AB  - BACKGROUND: Abnormally elevated alanine aminotransferase (ALT) of nonspecific
      causes is a common outpatient problem. Without considering ethnicity, several
      studies had suggested that it was associated with insulin resistance (IR).
      OBJECTIVE: To investigate whether nonspecific elevated ALT in Taiwanese
      population could reflect a likely underlying IR and was associated with impaired
      fasting glucose or type 2 diabetes mellitus (IFG/T2DM). METHODS: The health
      examination profiles of 1313 Taiwanese were investigated cross-sectionally. The
      prevalence and odds ratios (ORs) for IFG/T2DM and metabolic abnormalities in
      relation to elevated ALT were analyzed. RESULTS: Subjects with metabolic syndrome
      (MS) all had IFG/T2DM. The elevated ALT significantly correlated with MS and
      IFG/T2DM (i.e., 19.9-29.2% vs. 7.8% for MS, and 27.0-31.5% vs. 16.1% for
      IFG/T2DM). However, after excluding MS and adjustment for age and sex, the
      elevated ALT alone was not consistently associated with IFG/T2DM (36 < ALT <= 80
      IU/L with OR 0.97, 95% CI 0.58-1.61; 80 < ALT <= 120 IU/L with OR 0.55, 95% CI
      0.13-2.37; none with ALT > 120 had IFG). CONCLUSIONS: In a cross-sectional
      analysis of Taiwanese industrial employees, elevated ALT associated with MS, but
      in subjects who did not meet MS criteria, elevated ALT by itself did not
      associate with IFG/T2DM.

PMID- 21715039
TI  - The interplay of YKL-40 and leptin in type 2 diabetic obese patients.
AB  - Recently, YKL-40 has been identified as a new inflammatory marker of type 2
      diabetes mellitus (T2DM), while leptin is one of the most important adipose
      derived hormones. However, the relationship between them has not been elucidated.
      Therefore this study aimed to study their correlation in obese T2DM patients.

PMID- 21715040
TI  - Associations between glucose tolerance and sex hormone binding globulin among
      women with recent gestational diabetes mellitus.
AB  - We examined cross-sectional associations of sex hormone binding globulin (SHBG)
      with glucose among women recent GDM (n=55). SHBG was associated with fasting
      glucose levels before and after adjustment for covariates (p=0.015), but not with
      2-h glucose. We conclude SHBG should be explored in prospective studies in GDM
      women.

PMID- 21715041
TI  - Feasibility and preliminary efficacy of progressive resistance exercise training
      in lung cancer survivors.
AB  - Lung cancer survivors exhibit poor functional capacity, physical functioning, and
      quality of life (QoL). Here, we report the feasibility and preliminary efficacy
      of a progressive resistance exercise training (PRET) intervention in post
      treatment lung cancer survivors. Seventeen post-treatment lung cancer survivors
      (10 female), with a mean age of 67 (range 50-85), mean BMI of 25, and diagnosed
      with non-small cell lung cancer (94%) were recruited in Edmonton, Canada between
      August 2009 and August 2010 to undergo PRET. The primary outcomes focused on
      feasibility including eligibility and recruitment rate, loss to follow-up,
      measurement completion, exercise adherence, and program evaluation. Secondary
      outcomes addressed preliminary efficacy and included changes in muscular strength
      (1 repetition maximum), muscular endurance (repetitions at 70% of 1 repetition
      maximum), body composition (DXA scan), physical functioning (6-minute-walk-test,
      up-and-go, sit-to-stand, arm curls), and patient-reported outcomes including QoL
      (SF-36, FACT-L), fatigue (FACT-F), dyspnea (MRCD), and patient-rated function
      (LLFI). Forty of 389 lung cancer survivors were eligible (10%) and 17 of the 40
      (43%) were recruited. Over 80% of participants were able to complete all testing;
      two participants were lost to follow-up, and the median adherence rate was 96%
      (range: 25-100%). Ratings of testing burden were low (i.e., less than two out of
      seven for all items), and trial evaluation was high (i.e., greater than six out
      of seven for all measures). Paired t-tests showed significant increases in
      muscular strength (p<.001), muscular endurance (p<.001), six-minute walk distance
      (p<.001), up-and-go time (p<.05), number of arm curls (p<.001), and number of
      chair stands (p<.001). There were no significant changes in body composition or
      patient-reported outcomes. PRET is a feasible intervention with potential health
      benefits for a small proportion of lung cancer survivors in the post-treatment
      setting.

PMID- 21715042
TI  - Hypothesis testing in animal social networks.
AB  - Behavioural ecologists are increasingly using social network analysis to describe
      the social organisation of animal populations and to test hypotheses. However,
      the statistical analysis of network data presents a number of challenges. In
      particular the non-independent nature of the data violates the assumptions of
      many common statistical approaches. In our opinion there is currently confusion
      and uncertainty amongst behavioural ecologists concerning the potential pitfalls
      when hypotheses testing using social network data. Here we review what we
      consider to be key considerations associated with the analysis of animal social
      networks and provide a practical guide to the use of null models based on
      randomisation to control for structure and non-independence in the data.

PMID- 21715043
TI  - When are genes 'leaders' or 'followers' in evolution?

PMID- 21715044
TI  - Comprehensive analysis of TGF-beta and BMP receptor interactomes.
AB  - An immense number of cellular processes are initiated by cell surface
      serine/threonine kinase receptors belonging to the TGF-beta/BMP family.
      Subsequent downstream signalling cascades, as well as their crosstalk results in
      enormous specificity in terms of phenotypic outcome, e.g. proliferation,
      differentiation, migration or apoptosis. Such signalling diversity is achieved by
      the ability of receptors to interact with distinct proteins in a spatio-temporal
      manner. Following the cloning of the TGF-beta/BMP receptors a variety of
      different technologies were applied to identify such interacting proteins. Here
      we present a comprehensive survey of known interactome analyses, including our
      own data, on these receptors and discuss advantages and disadvantages of the
      applied technologies.

PMID- 21715045
TI  - Tree legumes as feedstock for sustainable biofuel production: Opportunities and
      challenges.
AB  - Concerns about future fossil fuel supplies and the environmental effects of their
      consumption have prompted the search for alternative sources of liquid fuels,
      specifically biofuels. However, it is important that the sources of such biofuel
      have minimal impact on global food supplies, land use, and commodity prices. Many
      legume trees can be grown on so-called marginal land with beneficial effects to
      the environment through their symbiotic interaction with "Rhizobia" and the
      associated process of root nodule development and biological nitrogen fixation.
      Once established legume trees can live for many years and some produce an annual
      yield of oil-rich seeds. For example, the tropical and sub-tropical legume tree
      Pongamia pinnata produces large seeds (~1.5-2g) that contain about 40% oil, the
      quality and composition of which is regarded as highly desirable for sustainable
      biofuel production. Here we consider the benefits of legume trees as future
      energy crops, particularly in relation to their impact on nitrogen inputs and the
      net energy balance for biofuel production, and also ways in which these as yet
      fully domesticated species may be further improved for optimal use as biofuel
      feedstock.

PMID- 21715046
TI  - [Keratoconus screening in a Lebanese students' population].
AB  - OBJECTIVE: Screening for keratoconus and potential risk factors in a medical
      student population in Lebanon using anterior topography. POPULATION AND METHODS:
      We randomly selected 110 medical students doing rotations in the Hotel-Dieu de
      France hospital in Lebanon between November 2009 and February 2010. Ninety-two
      students agreed to participate in the screening protocol, which included a
      questionnaire and an anterior topography. The topography was performed using the
      placido disk Tomey((r)) Topographic Modeling System TMS-4. The results were
      interpreted using the analysis programs supplied with the machine and by an
      experienced ophthalmologist. RESULTS: Ninety-two students participated in the
      study (83.6%): 49 males (53.2%) and 43 females (46.8%). The mean age was 23.6+/-1
      year. Fifty-eight students were ametropic (63.1%): 44 participants were myopic
      (47.8%), 40 had astigmatism (43.4%), and six were hyperopic (6.5%). Three
      students (six eyes) were diagnosed with keratoconus. The prevalence of
      keratoconus was 3.3%, of which 2.2% were already known cases. The prevalence of
      forme frustre keratoconus was 1.1%. Eleven students (12.1%) had a family history
      of keratoconus, only one was diagnosed with the disease. Atopy and eye rubbing
      were not found significantly related to keratoconus in this population.
      CONCLUSION: Keratoconus is a prevalent disease among our population of Lebanese
      medical students, which confirms the clinical impression that keratoconus is
      relatively frequent in Lebanon. Further studies need to be conducted on a larger
      and more representative sample to assess keratoconus prevalence and risk factors
      in Lebanon.

PMID- 21715047
TI  - De novo melanoma and melanoma arising from pre-existing nevus: in vivo
      morphologic differences as evaluated by confocal microscopy.
AB  - BACKGROUND: Although in the majority of melanomas there is no evidence of pre
      existing melanocytic nevus, it is believed that malignant transformation may
      sometimes occur within a benign precursor. OBJECTIVES: We sought to describe the
      morphologic features of de novo melanoma and melanoma arising from nevi by means
      of in vivo confocal microscopy, and to correlate them with their corresponding
      histopathologic features. METHODS: A total of 113 consecutive,
      histopathologically proven melanoma cases, 33 arising from a nevus and 80
      occurring de novo, were imaged by confocal microscopy and retrospectively
      evaluated. Cyto-architectural features preferentially expressed in melanomas
      arising from nevi and in de novo melanomas were defined. RESULTS: By confocal
      microscopy, abrupt transition, localized distribution of junctional atypical
      cells, and the presence of dense dermal nests were the most helpful criteria for
      categorizing a melanoma as arising from a nevus. Melanomas arising from common
      and congenital nevi were predominantly composed of roundish, monomorphous cells,
      whereas melanomas arising either de novo or from dysplastic nevi were
      characterized by markedly pleomorphic cells. LIMITATIONS: The study is
      retrospective. CONCLUSION: Confocal microscopy is effective in identifying
      melanoma even when a nevus is simultaneously present, confirming the clinical
      usefulness of this methodology. Moreover, distinctive features were observed in
      de novo melanomas and melanomas arising from nevi, permitting accurate
      distinction between the two groups. Finally, differences in cell morphology,
      easily detectable by confocal microscopy, seemed to characterize different
      melanoma types.

PMID- 21715048
TI  - Inadvertent insertion of nasogastric tube into the brain stem and spinal cord
      after endoscopic skull base surgery.
AB  - A significant number of neurosurgical patients require feeding tube placement via
      a nasogastric route. It is used as a temporary access for enteral feeding until
      patients are able to swallow or receive permanent access. Despite how commonly
      feeding tubes are used, they are not without potential complications. We report a
      case of inadvertent placement of small-bore feeding tube into the brain stem and
      spinal cord in a patient with a history of previous endoscopic transnasal
      resection of clival chordoma. We discuss the management of this complication and
      the strategies that have been developed to avoid this complication in the future.

PMID- 21715049
TI  - [Management of the male urethra before and after cystectomy: from the
      prophylactic urethrectomy to the intraoperative frozen section biopsy of the
      urethral margin].
AB  - CONTEXT: Decision making regarding the urethra before and after radical
      cystectomy due to urothelial carcinoma has always been controversial. OBJECTIVE:
      To analyze the changes produced in the management of the urethra from the
      beginning of the cystectomy up to the present moment. EVIDENCE ACQUISITION:
      Analysis of original articles and reviews obtained through a search in PubMed,
      related with the risk factors of urethral recurrence (UR) and with the management
      of the urethra in patients subjected to radical cystectomy. EVIDENCE SYNTHESIS:
      At first, many authors recommended urethrectomy simultaneously with cystectomy.
      The identification of risk factors of the bladder tumor related with the
      appearance of UR limited the indication of prophylactic urethrectomy in patients
      with multifocal disease and with prostate tumor involvement. The development of
      orthotopic bladder substitutes (OBS) complicated the situation. The involvement
      the prostatic urethral tumor was maintained as the principal risk factor for UR,
      which then gave importance to its pre-cystectomy staging. Series of OBS observed
      a lower incidence of UR regarding patients with skin derivations, even in cases
      with prostatic urethral involvement. Prostatic urethral involvement stopped being
      a contraindication for OBS when the frozen section biopsy of the urethral margin
      was negative. CONCLUSIONS: Currently, most authors agree that the intraoperative
      frozen section biopsy of the urethral margin will determine whether an OBS or
      urethrectomy should be performed. In spite of this, we have very few series in
      which this approach has been systematically used and with sufficient follow-up.

PMID- 21715050
TI  - [A foreign body in the upper airway. A vertebra in an unusual location].

PMID- 21715051
TI  - [Is it appropriate to admit elderly patients with pneumonia to short-stay
      units?].

PMID- 21715052
TI  - [Effects of a short proprioceptive training program in postural control in older
      people].

PMID- 21715053
TI  - [The Frailty Instrument for primary care of the Survey of Health, Ageing and
      Retirement in Europe (SHARE-FI): results of the Spanish sample].
AB  - BACKGROUND: Frailty is a syndrome with important epidemiological and clinical
      implications in older adults. One of the most accepted definitions of frailty is
      that of Fried and Walston, who operationalised it according to five well defined
      criteria. However, their criteria are not readily applicable in primary care,
      where practitioners need tools to identify patients who require priority access
      to more specialised resources. With that objective in mind, our research group
      published the Frailty Instrument of the Survey of Health, Ageing and Retirement
      in Europe (SHARE-FI). The present paper reports the results of the Spanish
      sample. METHODS: In the wave 1 of SHARE (2004), the Spanish sample was composed
      of 1,279 women and 933 men, all living in the community (mean age: 65.6 years).
      For each sex, a latent class analysis was used to summarise the five (adapted)
      frailty criteria into three incremental frailty classes. We tested the
      association of the frailty classes against a biopsychosocial range of wave 1
      variables; the predictive validity of the frailty classes was tested using
      mortality data from the second wave of SHARE (2006-2007), which were available
      for 846 women and 660 men. RESULTS: The frailty classes had the expected cross
      sectional associations. The age-adjusted Odds ratio for mortality (with 95%
      confidence interval) associated with the frail class was 3.2 (1.0-10.2) for women
      and 8.3 (3.1-22.1) for men. DISCUSSION: SHARE-FI is a valid and freely accessible
      instrument, which is intended to facilitate the adoption of the frailty paradigm
      in primary care.

PMID- 21715054
TI  - [Spanish pharmacovigilance system for vaccines].

PMID- 21715056
TI  - [III cranial nerve palsy and brainstem disfunction following retrobulbar
      anaesthesia].

PMID- 21715057
TI  - [The monitoring and control of sexually transmitted infections: a pending problem
      yet].

PMID- 21715058
TI  - [Tonka bean, gin tonic, Sintrom and creative cuisine: a case study].

PMID- 21715059
TI  - [Statistical Analysis of Rates and Trends (SART): a web-based tool for
      statistical calculation of population indicators].
AB  - We propose a web-based tool (SART: http://regstattools.net/sart.html) that
      automates calculations to obtain various population indicators that can be used
      for the control of diseases or health events. SART has four modules: a) a
      descriptive module that allows calculation of the number of cases and their
      percentage, the crude rate, the adjusted rate, the truncated rate and the
      cumulative rate; b) the estimated annual percentage change of rates; c)
      calculation of expected cases; and d) the standardized incidence of mortality
      ratio. SART requests a base file and input parameters from the user before
      processing the data. The data and the results obtained are processed and then
      sent by email to the user. The results are provided by sex and for each of the
      study variables (diseases, ethnic groups, geographic areas...) introduced into
      the base file.

PMID- 21715060
TI  - Increased syphilis trend among patients in an AIDS information and prevention
      center.
AB  - OBJECTIVE: A rebound of syphilis cases has recently been observed. This study
      describes the trend in syphilis infection among persons attending the AIDS
      information and prevention center of Valencia, Spain. METHODS: We performed a
      cohort study of all persons attended from 2000 to 2006. The calendar effect was
      assessed by a logistic regression model adjusted by sexual and sociodemographic
      variables. RESULTS: A total of 71% were heterosexuals (HT) and 19% were men who
      had sex with men (MSM). Among the 10,850 users of the center, the prevalence of
      syphilis was 0.7%. Among MSM, the prevalence of syphilis was 2.4% for the whole
      period and was 4.6% for 2006. Multivariate analysis showed that the risk of
      infection was lower in persons with a university education (OR=0.10; 95%CI: 0.03
      0.59) than in those without. The risk was higher in persons who took drugs
      (OR=5.49; 95%CI: 1.55-19.43) or who practiced prostitution (OR=6.83; 95%CI: 2.52
      18.53). In 2006, the risk of having syphilis was greater (OR=5.05; 95%CI: 1.12
      22.72). CONCLUSIONS: Syphilis infection increased substantially among MSM. In
      this collective, the prevalence of infection is related to educational level,
      prostitution and the use of non-injected recreational drugs.

PMID- 21715061
TI  - [Colorectal cancer screening: actions speak louder than words and the cart goes
      after the horse].

PMID- 21715062
TI  - [Gender and fiction: a window to history].

PMID- 21715063
TI  - [Colorectal cancer screening: foundations for making progress in screening in
      Spain].

PMID- 21715064
TI  - [Women's satisfaction with waiting times for further investigation in breast
      cancer screening].
AB  - OBJECTIVES: To determine the factors associated with satisfaction with waiting
      times for further investigation in breast cancer screening. METHODS: We carried
      out a cross-sectional study by telephone survey of a representative sample of
      women (N=316) participating in the breast cancer screening program of the
      autonomous region of Valencia (Spain) who required additional tests to confirm
      the diagnosis. Descriptive analysis was performed by contingency tables (p<0.05)
      and multivariate association by odds ratios (OR) of logistic regression models
      (95%CI). RESULTS: Satisfaction with the waiting time was 78.6%. A higher risk of
      dissatisfaction was found in women from a "high" social class (OR=3.17; 95% CI:
      1.10-9.14), those who perceived that the waiting time was "more than 2 weeks",
      both "since the notification of the need for further investigation until
      completion of the first test" (OR=15,54; 95%CI: 5,87-41,12) and "since the
      completion of the last test until notification of the final result" (OR=11.57;
      95% CI: 2.96-45.19), and in women who experienced the attention as "worse than
      expected" (OR=15.40; 95% CI: 1.41-168.64). The maximum waiting time acceptable to
      the highest percentage of women was "up to 1 week" for each waiting period (n=47,
      73.5%; n=14, 45.2%). CONCLUSIONS: Waiting times of no more than 1 week and never
      more than 2 weeks for each waiting period are recommended. Women should be given
      an approximate waiting time, paying special attention to women aged 45 to 54
      years attending their initial screening.

PMID- 21715065
TI  - [Management of needed health care workers in primary care. Automating the
      calculation].
AB  - The Santa Coloma de Gramenet Primary Care Service has designed a new tool to
      standardize and automate the process of planning the number of needed health care
      workers. The tool is divided in two parts: a calculator, which gives guidance on
      the foreseeable risk depending on the activity and the health care workers'
      workload, and sentinel indicators; the main is the "welfare basic level", that is
      the percentage structure of visited patients and their delay at 2, 3 and 7
      calendar days, assessing the impact on the care of the population. The results of
      its use in the summer of 2010 have demonstrated its efficiency by lowering the
      needed workers with respect to 2009, achieving a better distribution according to
      the workload and improving the economic management. Given that the necessary data
      are accessible through computerized databases and its simple use, we believe it
      to be exportable to other fields.

PMID- 21715066
TI  - Novel terpene based 1,4,2-dioxazoles: synthesis, characterization, molecular
      properties and screening against Entamoeba histolytica.
AB  - In present investigation a series of 20 dioxazole analogues (1-20) were
      synthesized, characterized and subjected to molecular properties prediction, anti
      amoebic screening and cytotoxicity evaluation. Out of the twenty compounds viz.
      3,5-substituted-1,4,2-dioxazoles, six compounds have shown IC(50) values in the
      range (1.00-1.10 MUM) lower than the standard drug metronidazole (IC(50) = 1.45
      MUM). The toxicological studies of the active compounds on H9c2 rat cardiac
      myoblasts showed that all compounds were nontoxic. The pKa, and log P values have
      also been predicted. Compound 8 showed the most promising results based on anti
      amoebic evaluation, cytotoxicity studies and physico-chemical properties
      prediction.

PMID- 21715067
TI  - Synthesis and pharmacological assessment of diversely substituted pyrazolo[3,4
      b]quinoline, and benzo[b]pyrazolo[4,3-g][1,8]naphthyridine derivatives.
AB  - The synthesis and pharmacological analyses of a number of pyrazolo[3,4
      b]quinoline and benzo[b]pyrazolo[4,3-g][1,8]naphthyridine derivatives are
      reported. We have synthesized the diversely substituted tacrine analogues 1-6, by
      Friedlander-type reaction of readily available o-amino-1-methyl-pyrazole
      dicarbonitriles with cyclohexanone. The biological evaluation showed that
      pyrazolotacrines 1-6 are inhibitors of Electrophorus electricus
      acetylcholinesterase (EeAChE), in the micromolar range, and quite selective in
      respect to serum horse butyrylcholinesterase (eqBuChE) inhibition; the most
      interesting inhibitor is N-(5-amino-1-methyl-6,7,8,9-tetrahydro-1H
      benzo[b]pyrazolo[4,3-g][1,8]naphthyridin-3-yl)acetamide (5) [IC(50) (EeAChE) =
      0.069 +/- 0.006 MUM; IC(50) (eqBuChE) = 6.3 +/- 0.6 MUM]. Kinetic studies showed
      that compound 5 is a mixed-type inhibitor of EeAChE (K(i) = 155 nM). Inhibitor 5
      showed a 45% neuroprotection value against rotenone/oligomycin A-induced neuronal
      death.

PMID- 21715068
TI  - Parotid gland disease in childhood: diagnosis and indications for surgical
      intervention.
AB  - We retrospectively analysed the clinicopathological profiles of all 9 patients
      aged 16 years and under who had had parotidectomies at York Hospital, UK from
      1995 to 2009. The operations were superficial parotidectomy (n=3), partial
      parotidectomy (n=4), and total parotidectomy with preservation of the facial
      nerve (n=2). The histological diagnoses were anomalies of the remnant of the
      branchial arch (n=4), and pleomorphic adenoma, haemangioma, cat scratch disease,
      juvenile chronic parotitis, and sarcoidosis (n=1 each) The histological diagnosis
      matched the clinical diagnosis in only 5. The most common complication (n=6) was
      transient weakness of the facial nerve. Various conditions that may be difficult
      to diagnose clinically can affect the parotid gland in young patients and require
      intervention. We describe our investigations, and indications for intervention in
      the management of parotid disease in children.

PMID- 21715069
TI  - Litterfall mercury dry deposition in the eastern USA.
AB  - Mercury (Hg) in autumn litterfall from predominately deciduous forests was
      measured in 3 years of samples from 23 Mercury Deposition Network sites in 15
      states across the eastern USA. Annual litterfall Hg dry deposition was
      significantly higher (median 12.3 micrograms per square meter (MUg/m(2)), range
      3.5-23.4 MUg/m(2)) than annual Hg wet deposition (median 9.6 MUg/m(2), range 4.4
      19.7 MUg/m(2)). The mean ratio of dry to wet Hg deposition was 1.3-1. The sum of
      dry and wet Hg deposition averaged 21 MUg/m(2) per year and 55% was litterfall
      dry deposition. Methylmercury was a median 0.8% of Hg in litterfall and ranged
      from 0.6 to 1.5%. Annual litterfall Hg and wet Hg deposition rates differed
      significantly and were weakly correlated. Litterfall Hg dry deposition differed
      among forest-cover types. This study demonstrated how annual litterfall Hg dry
      deposition rates approximate the lower bound of annual Hg dry fluxes.

PMID- 21715070
TI  - Spatial distribution and trends of total mercury in waters of the Great Lakes and
      connecting channels using an improved sampling technique.
AB  - Environment Canada recently developed a clean method suitable for sampling trace
      levels of metals in surface waters. The results of sampling for total mercury in
      the Laurentian Great Lakes between 2003 and 2009 give a unique basin-wide
      perspective of concentrations of this important contaminant and represent
      improved knowledge of mercury in the region. Results indicate that concentrations
      of total mercury in the offshore regions of the lakes were within a relatively
      narrow range from about 0.3 to 0.8 ng/L. The highest concentrations were observed
      in the western basin of Lake Erie and concentrations then declined towards the
      east. Compared to the offshore, higher levels were observed at some nearshore
      locations, particularly in lakes Erie and Ontario. The longer-term temporal
      record of mercury in Niagara River suspended sediments indicates an approximate
      30% decrease in equivalent water concentrations since 1986.

PMID- 21715071
TI  - Podocyte biology for the bedside.
AB  - The explosion of podocyte biology during the last decade has radically altered
      our views on the pathophysiologic process of proteinuria, glomerular disease, and
      progressive kidney disease. In this review, we highlight some of these landmark
      findings, but focus on recent advances in the field and implications for
      translating this biology into therapy for podocyte diseases.

PMID- 21715072
TI  - Red blood cell survival in long-term dialysis patients.
AB  - BACKGROUND: Shortening of red blood cell (RBC) survival contributes to the anemia
      of chronic kidney disease. The toxic uremic environment accounts for the
      decreased RBC life span. The contribution of mechanical damage caused by
      hemodialysis to the shortened life span is unclear. Reductions up to 70% in RBC
      survival have been reported in uremic patients. To date, no accurate well
      controlled RBC survival data exist in dialysis patients treated using different
      dialysis modalities and receiving erythropoiesis-stimulating agent (ESA) therapy.
      The aim of this study was to determine RBC survival in hemodialysis (HD) and
      peritoneal dialysis (PD) patients compared with healthy persons. STUDY DESIGN:
      Observational study. SETTING & PARTICIPANTS: 14 HD patients and 5 PD patients
      were recruited from the dialysis unit. Healthy volunteers (n = 14) age- and sex
      matched to HD participants were included. All dialysis patients received either
      ESA therapy or regular iron supplementation. PREDICTOR: Dialysis patients versus
      age- and sex-matched healthy controls. OUTCOMES: RBC survival. MEASUREMENTS: RBC
      survival was determined using radioactive chromium labeling. RESULTS: More than
      85% of dialysis patients were anemic (hemoglobin, 12.0 +/- 1.1 g/dL); hemoglobin
      concentrations were not significantly different between HD and PD patients.
      Median RBC survival was significantly decreased by 20% in HD patients compared
      with healthy controls: 58.1 (25th-75th percentile, 54.6-71.2) versus 72.9 (25th
      75th percentile, 63.4-87.8) days (P = 0.02). No difference was shown between the
      PD and HD groups: 55.3 (25th-75th percentile, 49.0-60.2) versus 58.1 (25th-75th
      percentile, 54.6-71.2) days (P = 0.2). LIMITATIONS: Label loss from RBCs
      associated with the chromium 51 labeling technique needs to be accounted for in
      the interpretation of RBC survival data. CONCLUSIONS: Despite current ESA
      therapy, decreased RBC survival contributes to chronic kidney disease-related
      anemia, although the reduction is less than previously reported. There does not
      appear to be net mechanical damage associated with HD therapy resulting in
      decreased RBC life span.

PMID- 21715073
TI  - Use of ultrasound to assess the response to therapy for secondary
      hyperparathyroidism.
AB  - Secondary hyperparathyroidism (SHPT) is a common complication in patients with
      chronic kidney disease. In SHPT, the biology of parathyroid cells changes
      significantly toward diffuse nodular hyperplasia. Currently, diagnosis of SHPT is
      based on intact parathyroid hormone serum levels and parameters of mineral
      metabolism. The morphologic diagnosis of SHPT relies on high-resolution
      ultrasonography with color Doppler imaging. This report describes a maintenance
      hemodialysis patient with severe SHPT treated using conventional therapy
      (phosphate binders and oral/intravenous vitamin D or analogues) and the
      subsequent addition of a calcimimetic. The role of color Doppler ultrasonography
      in the diagnosis, clinical follow-up, and assessment of therapeutic response of
      SHPT is discussed. This case suggests that the availability of calcimimetics has
      changed the natural history of clinical SHPT and may change the therapeutic
      utility of parathyroidectomy. Use of color Doppler ultrasonography further
      supports these therapeutic advances, allowing evaluation of the morphologic and
      vascular changes in hyperplastic parathyroid glands and aiding clinical,
      pharmacologic, and surgical strategies.

PMID- 21715074
TI  - Pharmacokinetics of multiple-dose levofloxacin in hemodialysis patients.

PMID- 21715075
TI  - [Management of nasolabial clefts: the issue in Dakar].
AB  - The management of patients with a cleft lip in developing countries is often the
      prerogative of humanitarian missions from developed countries. The goal of our
      work is to conduct a first epidemiological, clinical and therapeutic assessment
      of the management of cleft lips by a local team and to evidence the difficulties
      faced by us in our working conditions. In a retrospective study covering a period
      of about five years (January 2004 to March 2009), 205 cases of nasolabial clefts
      are assembled. The mean age at the time of the first visit is 17 months. A slight
      female predominance is observed. The majority of patients are from the capital
      city. A close relative with a cleft is found in 6.8% of them. In 44.9% of cases,
      it is a simple cleft lip. A cleft palate is associated in 47.8% of cases.
      Associated malformations are observed in 10.5% of cases. We operated on 110
      patients. The mean age at the first surgery is two years. Millard's technique is
      our technique of choice. No operative mortality is observed. In 17.4% of cases,
      operative morbidity occurred in the form of suppuration with partial or complete
      early suture release. The esthetic result is satisfactory in 67.7% of cases. This
      management could be improved by creating a multidisciplinary team including--in
      addition to surgeons--dentists, speech-language pathologists, psychologists, etc.

PMID- 21715076
TI  - Management and endovascular treatment of traumatic aortic rupture.

PMID- 21715077
TI  - Outcomes of coronary reimplantation for correction of anomalous origin of left
      coronary artery from pulmonary artery.
AB  - INTRODUCTION AND OBJECTIVES: We report our experience in the surgical correction
      of anomalous origin of left coronary artery from pulmonary artery (ALCAPA), with
      an emphasis on the coronary reimplantation technique and its outcome. METHODS: We
      designed a retrospective, longitudinal, descriptive study that included patients
      with ALCAPA who underwent surgery involving coronary reimplantation over a 19
      year period. We describe perioperative details such as variations in the surgical
      technique and the postoperative outcome in terms of morbidity and mortality.
      RESULTS: We studied 15 patients (86% females) with a mean age of 6.2 years
      (range, 2 months to 24 years). Heart failure was the principal cause for
      hospitalization in 80% of our patients. Left ventricular dysfunction was present
      in 67%, and 27% had significant or severe mitral valve regurgitation. We describe
      3 surgical techniques for coronary reimplantation, the choice of which depends on
      the site of origin of the anomalous left coronary artery. Four patients underwent
      an additional mitral valve procedure. The most common immediate postoperative
      complications were low cardiac output (38%), pleural effusion (17%), and
      transient ischemia (13%). There was no operative or medium-term mortality.
      CONCLUSIONS: Coronary reimplantation is the technique of choice for surgical
      correction of ALCAPA due to the excellent postoperative survival and low
      operative morbidity.

PMID- 21715078
TI  - When should we start enzyme replacement therapy for infantile Pompe disease with
      severe cardiomyopathy?

PMID- 21715079
TI  - [Percutaneous coronary intervention through an axillo-bifemoral bypass].

PMID- 21715080
TI  - Survival does not improve when therapeutic hypothermia is added to post-cardiac
      arrest care.
AB  - BACKGROUND: We investigated whether the use of therapeutic hypothermia improves
      the outcome after cardiac arrest (CA) under routine clinical conditions. METHOD:
      In a retrospective study, data of CA survivors treated from 2003 to 2010 were
      analysed. Of these, 143 patients were treated with hypothermia at 33 +/- 0.5
      degrees C for 24h according to predefined inclusion criteria, while 67 who did
      not fulfil these criteria received comparable therapy without hypothermia.
      RESULTS: 210 patients were included, 143 in the hypothermia group (HG) and 67 in
      the normothermia group (NG). There was no significant difference in mortality
      between the groups; 69 (48.2%) in the HG died in the first four weeks, compared
      to 30 patients (44.8%) in the NG (p=0.659). Patients in the NG were older and
      more seriously ill, and CA occurred more often in-hospital. Binary logistic
      regression revealed ventricular fibrillation (p=0.044), NSE serum level < 33 ng
      ml-1 (p<0.001), age (p=0.035) and witnessed cardiac arrest (p=0.043) as
      independent factors significantly improving survival after CA, whereas
      hypothermia was not (p=0.69). The target temperature was maintained for a
      significantly longer time (19.5h vs. 15.2h; p=0.003) in hypothermia patients with
      a favourable outcome than in those with an unfavourable outcome. CONCLUSION:
      There was no improvement in survival rates when hypothermia was added to standard
      therapy in this case series, as compared to standard therapy alone. The time at
      target temperature may be of relevance. We need better evidence in order to
      expand the recommendations for hypothermia after CA.

PMID- 21715081
TI  - Microarray based IgE detection in poly-sensitized allergic patients with
      suspected food allergy - an approach in four clinical cases.
AB  - BACKGROUND: Component-resolved diagnosis and microarray technology have been
      recently introduced into clinical allergy practice, and may be particularly
      useful in poly-sensitized allergic patients. METHODS: We compare the clinical
      usefulness of a microarray-based IgE detection assay (ISAC((r))) with skin tests
      and specific IgE with standard allergens (sIgE) or their monocomponents in four
      case reports of patients poly-sensitized to aeroallergens and food. RESULTS: Case
      1: a woman with rhinitis, oral allergy syndrome to several fruits and anaphylaxis
      to cherry. Diagnostic tests supported non-specific lipid transfer proteins
      (nsLTPs) primary sensitization. Case 2: a woman with exercise-induced asthma,
      rhino-conjunctivitis and oral allergy syndrome to fresh fruits of different
      families. A diagnosis of primary grass and weed pollen allergy with profilin and
      pathogenesis-related protein family 10 (PR-10) cross-reactive food allergy was
      proposed. Case 3: a man with atopic eczema, asthma, rhinitis, and multiple
      anaphylactic episodes with cashew nuts and oral allergy syndrome to fruits. The
      diagnostic workup supported a primary birch pollen allergy with PR-10 and nsLTPs
      cross-reactive food allergy. Case 4: a woman with rhino-conjunctivitis, per
      operative anaphylaxis due to latex and recent pharyngeal angio-oedema episodes.
      The diagnosis was a primary grass and weed pollen allergy with equivocal profilin
      sensitization and no obvious cross-reactivity mediated by nsLTPs sensitization.
      CONCLUSIONS: The possibility to carry out multiple sIgE measurements with single
      protein allergens, in particular with the microarray technique, is a useful,
      simple and non-invasive diagnostic tool in complex poly-sensitized allergic
      patients.

PMID- 21715083
TI  - Household use of and satisfaction with alternative water sources in Victoria
      Australia.
AB  - Climate change is increasing the variability of rainfall, and thus the
      availability of water supplies in many areas of the world. These impacts are
      already being felt in the state of Victoria, Australia where a 12 year drought
      period was recently experienced. Restrictions to water use have been implemented,
      as one component of a broad policy approach to manage the drought. While
      anecdotal evidence suggests that the substitution of centralised water supplies
      is occurring, this has not been proven empirically. This paper reports results
      from a survey of households in Victoria regarding their use of alternative water
      sources. The study found that substitution is occurring. Garden watering is the
      purpose which has the highest rate of alternative water source use. In total
      41.6% of respondents always, and 33.2% sometimes use an alternative water source
      for garden watering. The most commonly used alternative source of water for
      garden watering is water previously used in the laundry (30.7%). The alternative
      source of water used was found to vary depending on the purpose of the water use.
      High levels of satisfaction were found for all alternative water sources used.
      Several barriers were found to the use of alternative water sources, the main of
      which were: inflexibility of existing infrastructure, cost, policy, and housing
      status. The results have implications for water retailers, policy makers and
      governments in locations facing water shortage.

PMID- 21715082
TI  - In vivo tests of thermodynamic models of transcription repressor function.
AB  - One emphasis of the Gibbs Conference on Biothermodynamics is the value of
      thermodynamic measurements for understanding behaviors of biological systems. In
      this study, the correlation between thermodynamic measurements of in vitro DNA
      binding affinity with in vivo transcription repression was investigated for two
      transcription repressors. In the first system, which comprised an engineered
      LacI/GalR homolog, mutational changes altered the equilibrium constant for
      binding DNA. Changes correlated with altered repression, but estimates of in vivo
      repressor concentration suggest a >=25-fold discrepancy with in vitro conditions.
      In the second system, changes in ligand binding to BirA altered dimerization and
      subsequent DNA occupancy. Again, these changes correlate with altered in vivo
      repression, but comparison with in vitro measurements reveals a ~10-fold
      discrepancy. Further analysis of each system suggests that the observed
      discrepancies between in vitro and in vivo results reflect the contributions of
      additional equilibria to the transcription repression process.

PMID- 21715084
TI  - SRD5A polymorphisms and biochemical failure after radical prostatectomy.
AB  - BACKGROUND: The relationship between inherited germ-line variations in the 5alpha
      reductase pathways of androgen biosynthesis and the risk of biochemical
      recurrence (BCR) after radical prostatectomy (RP) remains an unexplored area.
      OBJECTIVE: To determine the link between germ-line variations in the steroid
      5alpha-reductase, alpha-polypeptide 1 (SRD5A1) and steroid-5alpha-reductase,
      alpha-polypeptide 2 (SRD5A2) genes and BCR. DESIGN, SETTINGS, AND PARTICIPANTS:
      We studied retrospectively two independent cohorts composed of 526 white (25%
      BCR) and 320 Asian men (36% BCR) with pathologically organ-confined prostate
      cancer who had a median follow-up of 88.8 and 30.8 mo after surgery,
      respectively. MEASUREMENTS: Patients were genotyped for 19 haplotype-tagging
      single nucleotide polymorphisms (htSNPs) in SRD5A1 and SRD5A2 genes, and their
      prognostic significance on prostate-specific antigen recurrence was assessed
      using Kaplan-Meier analysis and the Cox regression model. RESULTS AND
      LIMITATIONS: After adjusting for all clinicopathologic risk factors, four SNPs
      (rs2208532, rs12470143, rs523349, and rs4952197) were associated with BCR in both
      whites and Asians. The strongest effect was conferred by the SRD5A2 V89L
      nonsynonymous SNP (rs523349C) with a hazard ratio (HR) of 2.87 (95% confidence
      interval [CI], 2.07-4.00; p = 4 * 10-10; 48% BCR). In addition, in whites, the
      combination of two SNPs, rs518673T in SRD5A1 and rs12470143A in SRD5A2, was
      associated with a reduced BCR rate for carriers of three or four alleles (HR:
      0.37; 95% CI, 0.19-0.71; p=0.003;16% BCR) compared with noncarriers (38% BCR),
      whereas the SRD5A2 rs12470143A was significant in Asians (HR: 0.46; 95% CI, 0.28
      0.73; p=0.001). Limitations of our study include few events of androgen
      deprivation resistance or cancer-specific death. CONCLUSIONS: Our study is the
      first to show positive associations of several SRD5A1 and SRD5A2 variations as
      independent predictors of BCR after RP.

PMID- 21715085
TI  - Postoperative intravesical therapy to prevent bladder tumor recurrence: are we
      ready to listen yet?

PMID- 21715086
TI  - Evaluating the value of number of cycles of docetaxel and prednisone in men with
      metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: The optimal number of 3-wk docetaxel plus prednisone (DP) cycles for
      metastatic castration-resistant prostate cancer (mCRPC) is unclear. OBJECTIVE: A
      retrospective analysis of two clinical trials was performed to evaluate the
      association of the number of cycles with overall survival (OS). DESIGN, SETTING,
      AND PARTICIPANTS: An exploratory analysis compared outcomes of 332 men who
      received DP in the TAX-327 trial, which stipulated up to 10 cycles, and 220 men
      who received DP in CS-205, a randomized phase 2 trial comparing DP plus AT-101
      (bcl-2 inhibitor) versus DP plus placebo, which allowed up to 17 cycles.
      MEASUREMENTS: Patients who completed 10 cycles of DP without progression in both
      trials were included. Men in both arms of CS-205 were combined for analysis, as
      no significant differences in outcomes were observed. OS was estimated from the
      date of cycle 10 docetaxel infusion. RESULTS AND LIMITATIONS: The number of men
      receiving 10 cycles was similar (p=0.26) in the two trials (166 [50.0%] in TAX
      327 vs 99 [45.0%] in CS-205; the latter group received a median of five
      additional cycles). Six- and 12-mo estimated survival after cycle 10 was 92.2%
      (95% confidence interval [CI], 86.9-95.4%) and 74.6% (CI, 67.2-80.5%) in TAX-327,
      compared with 92.8% (CI, 85.5-96.5) and 63.4% (CI, 51.8-72.9%) in CS-205.
      Subanalyses suggested that <10 cycles may have a negative impact and prostate
      specific antigen (PSA) declines at cycle 10 may carry a favorable impact. The
      significance of continued PSA declines up to 17 cycles is unclear. Limitations of
      a retrospective analysis apply. CONCLUSIONS: A survival benefit was not detected
      with >10 cycles of DP in men with mCRPC in this retrospective hypothesis
      generating analysis.

PMID- 21715087
TI  - Phytochelatin synthase activity as a marker of metal pollution.
AB  - The synthesis of phytochelatins is catalyzed by gamma-Glu-Cys dipeptidyl
      transpeptidase called phytochelatin synthase (PCS). Aim of this study was to
      suggest a new tool for determination of phytochelatin synthase activity in the
      tobacco BY-2 cells treated with different concentrations of the Cd(II). After the
      optimization steps, an experiment on BY-2 cells exposed to different
      concentrations of Cd(NO(3))(2) for 3 days was performed. At the end of the
      experiment, cells were harvested and homogenized. Reduced glutathione and cadmium
      (II) ions were added to the cell suspension supernatant. These mixtures were
      incubated at 35 degrees C for 30min and analysed using high performance liquid
      chromatography coupled with electrochemical detector (HPLC-ED). The results
      revealed that PCS activity rises markedly with increasing concentration of
      cadmium (II) ions. The lowest concentration of the toxic metal ions caused almost
      three fold increase in PCS activity as compared to control samples. The activity
      of PCS (270fkat) in treated cells was more than seven times higher in comparison
      to control ones. K(m) for PCS was estimated as 2.3mM.

PMID- 21715088
TI  - Bioreduction of para-chloronitrobenzene in drinking water using a continuous
      stirred hydrogen-based hollow fiber membrane biofilm reactor.
AB  - para-Chloronitrobenzene (p-CNB) is particularly harmful and persistent in the
      environment and is one of the priority pollutants. A feasible degradation pathway
      for p-CNB is bioreduction under anaerobic conditions. Bioreduction of p-CNB using
      a hydrogen-based hollow fiber membrane biofilm reactor (HFMBfR) was investigated
      in the present study. The experiment results revealed that p-CNB was firstly
      reduced to para-chloraniline (p-CAN) as an intermediate and then reduced to
      aniline that involves nitro reduction and reductive dechlorination with H(2) as
      the electron donor. The HFMBfR had reduced p-CNB to a major extent with a maximum
      removal percentage of 99.3% at an influent p-CNB concentration of 2mg/L and a
      hydraulic residence time of 4.8h, which corresponded to a p-CNB flux of
      0.058g/m(2) d. The H(2) availability, p-CNB loading, and the presence of
      competing electron acceptors affected the p-CNB reduction. Flux analysis
      indicated that the reduction of p-CNB and p-CAN could consume fewer electrons
      than that of nitrate and sulfate. The HFMBfR had high average hydrogen
      utilization efficiencies at different steady states in this experiment, with a
      maximum efficiency at 98.2%.

PMID- 21715089
TI  - High efficiency removal of dissolved As(III) using iron nanoparticle-embedded
      macroporous polymer composites.
AB  - Novel nanocomposite materials where iron nanoparticles are embedded into the
      walls of a macroporous polymer were produced and their efficiency for the removal
      of As(III) from aqueous media was studied. Nanocomposite gels containing alpha
      Fe(2)O(3) and Fe(3)O(4) nanoparticles were prepared by cryopolymerisation
      resulting in a monolithic structure with large interconnected pores up to 100 MUm
      in diameter and possessing a high permeability (ca. 3 * 10(-3) ms(-1)). The
      nanocomposite devices showed excellent capability for the removal of trace
      concentrations of As(III) from solution, with a total capacity of up to 3mg As/g
      of nanoparticles. The leaching of iron was minimal and the device could operate
      in a pH range 3-9 without diminishing removal efficiency. The effect of competing
      ions such as SO(4)(2-) and PO(4)(3-) was negligible. The macroporous composites
      can be easily configured into a variety of shapes and structures and the polymer
      matrix can be selected from a variety of monomers, offering high potential as
      flexible metal cation remediation devices.

PMID- 21715090
TI  - Synthesis and characterization of monodispersed orthorhombic manganese oxide
      nanoparticles produced by Bacillus sp. cells simultaneous to its bioremediation.
AB  - A heavy metal resistant strain of Bacillus sp. (MTCC10650) is reported. The
      strain exhibited the property of bioaccumulating manganese, simultaneous to its
      remediation. The nanoparticles thus formed were characterized and identified
      using energy dispersive X-ray analysis (EDAX), high resolution transmission
      electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), powder X-ray
      diffraction (PXRD) and atomic force microscopy (AFM). When the cells were
      challenged with manganese, the cells effectively synthesized nanoparticles of
      average size 4.62+/-0.14nm. These were mostly spherical and monodispersed. The ex
      situ enzymatically synthesized nanoparticles exhibited an absorbance maximum at
      329nm. These were more discrete, small and uniform, than the manganese oxide
      nanoparticles recovered after cell sonication. The use of Bacillus sp. cells
      seems promising and advantageous approach. Since, it serves dual purposes of (i)
      remediation and (ii) nanoparticle synthesis. Considering the increasing demand of
      developing environmental friendly and cost effective technologies for
      nanoparticle synthesis, these cells can be exploited for the remediation of
      manganese from the environment in conjunction with development of a greener
      process for the controlled synthesis of manganese oxide nanoparticles.

PMID- 21715091
TI  - Oxolane-2,5-dione modified electrospun cellulose nanofibers for heavy metals
      adsorption.
AB  - Functionalized cellulose nanofibers have been obtained through electrospinning
      and modification with oxolane-2,5-dione. The application of the nanofibers for
      adsorption of cadmium and lead ions from model wastewater samples is presented
      for the first time. Physical and chemical properties of the nanofibers were
      characterized. Surface chemistry during preparation and functionalization was
      monitored using Fourier transform-infrared spectroscopy, scanning electron
      microscopy, carbon-13 solid state nuclear magnetic resonance spectroscopy and
      Brunauer Emmett and Teller. Enhanced surface area of 13.68m(2)g(-1) was recorded
      for the nanofibers as compared to the cellulose fibers with a surface area of
      3.22m(2)g(-1). Freundlich isotherm was found to describe the interactions better
      than Langmuir: K(f)=1.0 and 2.91mmol g(-1) (r(2)=0.997 and 0.988) for lead and
      cadmium, respectively. Regenerability of the fiber mats was investigated and the
      results obtained indicate sustainability in adsorption efficacy of the material.

PMID- 21715092
TI  - Solidification of cement kiln dust using sulfur binder.
AB  - The present study aims to offer a new methodology for consuming two industrial
      wastes; sulfur, from petroleum and natural gas industries, and cement kiln dust
      (CKD), from Portland cement industries, in construction industry. Sulfur
      solidified cement kiln dust material (SSCKDM) was manufactured by mixing molten
      sulfur, treated sulfur, CKD and sand at a controlled temperature in excess of 120
      degrees C. The hot mixture was subsequently cast and shaped into the desired mold
      and was then allowed to solidify at a specified cooling rate. Solidified
      materials were immersed for time periods up to 28 days in distilled water at
      different temperatures of 25 and 60 degrees C, sea water, and acidic and basic
      universal buffer solutions of pH4 and pH9, respectively. Solidified material
      performance as function of time and type of aqueous solution exposed to was
      evaluated in view of compressive strength variations and leachability of metal
      and heavy metal ions. The results indicated that the solidified articles exhibit
      homogenous and compact internal microstructure with excellent mechanical
      properties. However, it showed durability problem upon exposure to aqueous
      solution environments due to the initial chemical composition of the CKD, whose
      leached test showed release of relatively high amounts of sulfates and alkali
      metals. Durability of SSCKDM articles in relation to strength reduction and crack
      formations control was improved by addition of glass fiber while, the use of anti
      leaching agent such as anhydrous sodium sulfide resulted in reduction of leached
      heavy metals without any measurable decrease in leached amounts of alkali metals
      and anions from the solidified matrix. Furthermore, based on leachability index
      method of calculation, potential chemical mobility of metal and heavy metal ions
      from the solidified matrix was characterized as medium.

PMID- 21715093
TI  - Sequential ASE extraction of alkylphenols from sediments: Occurrence and
      environmental implications.
AB  - The occurrence of alkylphenols (APs) including nonylphenol (NP) and octylphenol
      (OP) in the riverine sediments from the Pearl River Delta (PRD), South China was
      investigated and compared by Soxhlet extraction (S-APs) with dichloromethane and
      by sequential accelerated solvent extraction (ASE) (A-APs) with 1:6
      toluene/methanol, respectively. Concentrations of OP and NP range from <1 to
      463ng/g dw and 31-21,885ng/g dw, respectively, demonstrating that the
      contamination level of APs in the PRD is one of the highest in the world.
      Moreover, the A-APs contents are highly significantly related to and on average
      1.5 times the S-APs contents. For sequential two ASE extractions, APs in the
      first extract accounts for 82.2-99.2% of their total contents in the sequential
      two extractions. The correlation analysis shows that S-APs and A-APs are both
      significantly associated with the contents of total organic carbon (TOC),
      suggesting that the variable extraction efficiency of these two methods is
      related to the presence of condensed organic matter in the sediments.

PMID- 21715094
TI  - Observation-based assessment of functional ability in patients with chronic
      widespread pain: a cross-sectional study.
AB  - Knowledge about functional ability, including activities of daily living (ADL),
      in patients with chronic widespread pain (CWP) and fibromyalgia (FMS) is largely
      based on self-report. The purpose of this study was to assess functional ability
      by using standardised, observation-based assessment of ADL performance and to
      examine the relationship between self-reported and observation-based measures of
      disability. A total of 257 women with CWP, 199 (77%) fulfilling the American
      College of Rheumatology tender point criteria for FMS, were evaluated with the
      Assessment of Motor and Process Skills (AMPS), an observation-based assessment
      providing linear measures of ADL motor and ADL process skill ability (unit:
      logits). A cutoff for effortless and independent ADL task performance is set at
      2.0 for the motor scale and 1.0 for the process scale. A total of 248 (96.5%) had
      ability measures below the 2.00 ADL motor cutoff and 107 (41.6%) below the 1.00
      ADL process cutoff, indicating increased effort and/or inefficiency during task
      performance as well as a potential need of assistance for community living. Mean
      ADL motor ability measure was 1.07 and was significantly lower in patients
      diagnosed with FMS than plain CWP (1.02 vs 1.27 logits, P=.001). Mean ADL process
      ability measure was 1.09 logits and was without difference between FMS and plain
      CWP (1.07 vs 1.16 logits, P=.064). Only weak to moderate correlations between
      self-reported functional ability and observation-based AMPS ability measures were
      observed. The results of the study support the notion of considerable performance
      difficulties in women with CWP. The everyday life problems are substantial and
      place the individual at risk of need of support for community living.

PMID- 21715095
TI  - Simultaneous quantification of the relative abundance of species complex members:
      application to Culicoides obsoletus and Culicoides scoticus (Diptera:
      Ceratopogonidae), potential vectors of bluetongue virus.
AB  - The two sympatric sibling species Culicoides obsoletus (Meigen) and Culicoides
      scoticus Downes and Kettle (Diptera: Ceratopogonidae), are known to be competent
      vectors for bluetongue virus in the Palaearctic region. However, morphological
      identification of constituent species is only readily applicable to adult males
      and these two species distinguishing traits have overlapping character states. As
      their vector competence may differ in space and time, the correct identification
      and quantification of specimens of both species are essential for understanding
      bluetongue epidemiology. However, no molecular tools are available for high
      throughput identification of the two species. We therefore developed a
      quantitative duplex real-time PCR assay to determine the relative abundance of
      each sibling species in a sample using TaqMan probes. For each species, standard
      curves were constructed from serial dilutions of purified plasmid DNA containing
      ITS1-5.8S-ITS2 (rDNA) in the range of 10(-1) to 10(-5)ng/MUL. Standard curves
      were used to quantify samples of mixed C. obsoletus/C. scoticus specimens.
      Specificity was evaluated with 5156 specimens representing 62 species. Based on
      the DNA quantities detected according to the standard curves, a quadratic model
      developed on 1100 males and validated on 555 females was able to predict the
      relative abundance of each species simultaneously in a one-shot reaction (Pearson
      coefficient of 0.999). Our assay showed a requirement of two specimens or less
      for 95% of the predictions, making it highly applicable to field collections.
      Extensive use of this real-time PCR assay will provide a better understanding of
      geographical distribution, dynamics, and bionomics on a species level, which is
      essential for risk assessment. This approach is an important contribution to
      medical entomology for investigating the vector role of arthropod sibling
      species.

PMID- 21715096
TI  - Cryptosporidium parvum infection in a mare and her foal with foal heat diarrhoea.
AB  - Cryptosporidium infection was molecularly investigated in mares and in their
      neonatal foals for which the occurrence of foal heat diarrhoea was also assessed.
      Thirty-seven mare/foal pairs were included in the study. All foals were born in
      the same stud farm during 2006-2008 breeding seasons. Two faecal samples, one
      prior to and one after delivery were collected from each mare, whereas three
      faecal samples were taken from each foal, i.e. at 8, 10 and 12 days of age. All
      samples (74 from mares and 111 from foals) were divided into two aliquots, one of
      which was examined for the presence of Cryptosporidium by a commercially
      available microplate ELISA kit, while the second aliquot of all ELISA-positive
      samples was molecularly examined. Nine out of 37 examined foals presented foal
      heat diarrhoea and one of them scored positive for Cryptosporidium, together with
      its mare. More specifically, four samples belonging to the same mare/foal pair
      resulted positive for Cryptosporidium upon both ELISA and PCR. The sequence
      analysis of the COWP gene showed the occurrence of the zoonotic species
      Cryptosporidium parvum. The possibility that foal heat diarrhoea-like episodes
      may be due to neonatal cryptosporidiosis and their relevance for the health of
      horses and of humans handling diarrhoeic neonatal foals and their mares are
      discussed.

PMID- 21715097
TI  - Characterization of acid phosphatase from the tick Haemaphysalis longicornis.
AB  - The full-length cDNA encoding acid phosphatase (HL-3) from Haemaphysalis
      longicornis was obtained by 5' rapid amplification of cDNA ends (RACE). The cDNA
      contained a 1137 bp open reading frame (ORF) coding for 356 amino acids with a
      predicted theoretical isoelectric point (pI) of 6.35 and molecular weight of 41.0
      kDa. The recombinant protein was expressed in Escherichia coli. The enzyme could
      hydrolyze para-nitrophenyl phosphate (pNPP) substrate at an optimum pH of 5.0.
      Real-time RT-PCR analysis showed that the HL-3 transcripts were expressed in
      various stages of unfed ticks and were significantly induced by blood feeding.
      Furthermore, the expression of HL-3 in midguts was significantly higher than in
      other tested tissues of partially fed adult ticks. The transcripts of the HL-3
      mRNA in lipopolysaccharide (LPS)-injected ticks were 1.75 times of the PBS
      injected control; Theileria sergenti infected larvae expressed 3.86 more times
      than that of uninfected ones. Western blot analysis showed that rabbit antiserum
      against the recombinant rHL-3 could recognize a native protein of approximately
      41.0 kDa in the lysates from different stages of ticks. Vaccination of rabbits
      with the rHL-3 conferred partial protective immunity against ticks, resulting in
      28% mortality and 10.6% reduction in engorgement weight of adult ticks,
      respectively. These results suggested that the HL-3 was involved in tick innate
      immunity and could be used as a potential candidate antigen for the development
      of anti-tick vaccines.

PMID- 21715098
TI  - Infiltration of sodium valproate with compartment syndrome and bullous reaction:
      case report and literature review.

PMID- 21715099
TI  - Defective homologous recombination in human cancers.
AB  - Homologous recombination (HR) is a process by which DNA double strand breaks are
      repaired through the alignment of homologous sequences of DNA. Interest continues
      to increase in HR pathway function due to the development of new therapeutic
      agents which selectively exploit DNA damage repair pathways. Currently the most
      promising of these new agents are inhibitors of poly(ADP ribose) polymerase
      (PARP). The response of cancers known to be deficient in HR, due to BRCA1 or 2
      mutations has been demonstrated, and a wider use of PARP inhibitors in cancers
      with mutations of other HR pathway genes has been suggested. With ongoing
      clinical studies into the use of PARP inhibitors, further understanding of the HR
      pathway, to allow patient selection by cancer biology, is now essential. Numerous
      studies have investigated individual aberrations of genes involved in the HR
      pathway. Here we collate this evidence to give an overview of the role of the HR
      pathway in human cancer.

PMID- 21715100
TI  - Recent clinical developments and rationale for combining targeted agents in non
      small cell lung cancer (NSCLC).
AB  - While chemotherapy has been the standard of care for patients with advanced non
      small cell lung cancer (NSCLC), efforts have shifted toward evaluating novel
      targeted agents in an attempt to improve outcome. These targeted agents are
      directed toward key components in several signalling pathways such as vascular
      endothelial growth factor receptor (VEGFR), platelet-derived growth factor
      receptor (PDGFR), epidermal growth factor receptor (EGFR) and insulin-like growth
      factor 1 receptor (IGF-IR). There is also increasing interest in using
      combinations of targeted agents to inhibit more than one pathway; for example,
      inhibition of VEGFR + EGFR and VEGFR + PDGFR + EGFR. Further investigation is
      needed to identify the most appropriate combinations of these targeted agents in
      select patient subgroups, and to define optimal treatment doses to thereby
      achieve the best therapeutic index. This review outlines the rationale for
      combining targeted agents for the treatment of advanced NSCLC.

PMID- 21715101
TI  - Physiological and behavioral adaptation to relocation stress in differentially
      reared rhesus monkeys: hair cortisol as a biomarker for anxiety-related
      responses.
AB  - Increased hair cortisol concentrations have been associated with stress exposure
      in both human and nonhuman primates, and hair cortisol is now gaining attention
      as a biomarker for stress-related health problems. The present study examined the
      behavioral and physiological reactions of rhesus monkey (Macaca mulatta) infants
      reared in three different rearing environments to the major stressor of
      relocation. Infant monkeys (n=61) were studied from birth through 2 years of age.
      For the first 8 months of life, infants were either with their mothers and peers
      (MPR, n=21) or reared in a nursery using either peer-rearing (PR, n=20) or
      surrogate-peer-rearing (SPR, n=20). At approximately 8 months of age, infants
      were removed from their rearing group, simultaneously placed into a large social
      environment consisting of infants from all three rearing conditions, and observed
      for the next 16 months. Behavior was recorded twice per week from 1 to 24 months,
      and composite anxiety scores were calculated for each monkey. Monkeys were
      initially shaved at the nape of the neck on day 14 to remove any prenatal effects
      on hair cortisol deposition. Hair samples were then collected by re-shaving at 6,
      12, 18 and 24 months and analyzed for cortisol content. MPR monkeys were the
      least affected by the stressor, showing smaller increases in anxious behavior
      than the other groups and more rapid physiological adaptation as assessed using
      hair cortisol. PR monkeys showed heightened and prolonged anxious behavior, had
      the highest cortisol levels prior to relocation, and their cortisol levels did
      not decline until more than a year later. SPR monkeys exhibited more rapid
      behavioral adaptation than PR monkeys, showing heightened but not prolonged
      anxious behavior. However, the SPR group showed a marked increase in cortisol in
      response to the relocation, and like the PR group, their physiological adaptation
      was slower than that of the MPR group as indicated by elevated cortisol levels at
      18 months. By 24 months of age (16 months after relocation), all rearing groups
      were indistinguishable from one another physiologically and behaviorally.
      Spearman rank correlation revealed that hair cortisol taken at month 6 was not
      correlated with composite anxiety scores from months 6 to 8 (just before the
      relocation), but was positively correlated with composite anxiety scores between
      months 8 and 12 (immediately after relocation) for PR infants only (r(s)=0.75,
      p<0.001). Month 6-hair cortisol tended to positively correlate with composite
      anxiety scores for the following 6 months (months 12-18) for PR monkeys only
      (r(s)=0.47, p=0.037), which exhibited more anxious behavior than MPR and SPR
      infants during this period (ANOVA: F((2,60))=14.761, p<0.001) This is the first
      study to show that elevated hair cortisol early in life is a biomarker for the
      later development of anxious behavior in response to a major life stressor,
      particularly for infant monkeys exposed to early life adversity in the form of
      peer-rearing.

PMID- 21715102
TI  - Radius fracture repair using volumetrically expanding polyurethane bone cement.
AB  - PURPOSE: New repair techniques for fragility fractures such as those of the
      distal radius require biomechanical justification. This study was conducted to
      investigate a technique using an expanding polymer bone cement to provide
      strength to a fracture repair. METHODS: Distal and proximal ends were isolated
      from 6 pairs of human radii (mean age 65). Transverse osteotomies were made near
      the head of each specimen. Paired specimens were repaired using 2 materials of
      differing polymer chemistries: polyurethane versus polymethylmethacrylate.
      Repaired specimens were subjected to failure tests in a cantilever beam
      configuration (distal, n = 6 per treatment) or pure tension (proximal, n = 5 per
      treatment). Cement penetration tests were conducted using a uniform open-cell
      model of cancellous bone. Baseline mechanical properties of the polyurethane
      cement were determined according to ASTM standards. RESULTS: Distal radii
      repaired with polyurethane bone cement withstood average shear stress 2.9 times
      as high as polymethylmethacrylate (0.91 vs 0.31 MPa). Peak tensile bending stress
      was 2.5 times as high in polyurethane (2.57 vs 1.02 MPa). Under pure tension,
      polyurethane-repaired samples failed at 0.83 MPa versus 0.74 MPa for
      polymethylmethacrylate. The polyurethane cement expanded to penetrate 49% farther
      into the trabeculae. The polyurethane cement had mean compressive yield stress of
      20.3 MPa, compressive modulus of 754 MPa, ultimate tensile stress of 18.5 MPa,
      and tensile elastic modulus of 723 MPa. CONCLUSIONS: The biomechanical strength
      data indicate the potential of an expanding bone cement as a candidate strategy
      for fracture repair. Further evaluation might provide evidence for such an
      alternative repair strategy for fragility fractures, including those of the
      distal radius.

PMID- 21715104
TI  - The relationship between ASSH membership and the treatment of distal radius
      fracture in the United States Medicare population.
AB  - PURPOSE: Internal fixation for distal radius fractures (DRFs) in the elderly has
      increased from 3% in 1997 to 17% in 2007. This increase has been uneven across
      regions of the United States. There is some evidence that patients treated by
      hand surgeons receive internal fixation at an increased rate and that hand
      surgeons might be driving the increased usage in regions where their presence is
      greatest. The specific aim of this study was to explore this relationship by
      analyzing Medicare beneficiaries treated by members of the American Society for
      Surgery of the Hand (ASSH). METHODS: Surgeons who were members of ASSH in 2007
      were matched with surgeons treating Medicare beneficiaries for DRFs in the same
      year. We then fit a series of multilevel models to estimate the proportion of
      total variance in internal fixation usage explained by ASSH membership status,
      patient demographic data, patient comorbidity, and/or type of fracture diagnosed.
      RESULTS: Beneficiaries treated by ASSH members received internal fixation
      significantly more often than beneficiaries who were treated by surgeons who were
      not ASSH members. ASSH member status accounts for 12% of the total variance in
      internal fixation utilization. CONCLUSIONS: Medicare beneficiaries who were
      treated by ASSH member surgeons receive internal fixation at a significantly
      higher rate than do patients of other physicians. When there is uncertainty about
      the optimal treatment for a condition, there is the possibility for specialty
      related disparities. This specialty effect contributes to the national variations
      in the treatment of DRFs in the Medicare population.

PMID- 21715105
TI  - Prolonged use of benzodiazepines is associated with childhood trauma in opioid
      maintained patients.
AB  - BACKGROUND: Benzodiazepine (BZD) misuse in opioid-maintained patients is
      widespread and has been related to poorer treatment success. Associated factors,
      in particular, traumatic childhood experiences, have not been investigated
      extensively. METHODS: Cross-sectional survey including the childhood trauma
      questionnaire (CTQ) and clinical data among 193 patients prescribed oral opioids
      or injectable diacetylmorphine for opioid dependence. RESULTS: BZD use was
      prevalent (61%) and the burden of childhood traumatic experiences was high with
      67% reporting at least one trauma subscore of moderate-to-severe level. In
      univariate analysis, CTQ-subcategories "emotional abuse" (p<0.05), "emotional
      neglect" (p<0.01) and "physical neglect" (p<0.001) were significantly associated
      with prolonged BZD use. In multivariate analysis, prolonged BZD use was
      associated with categorized overall CTQ-scores (OR 1.5), HCV-seropositivity (OR
      4.0), psychiatric family history (OR 2.3), and opioid dose (mg methadone
      equivalents, OR 1.010). CONCLUSIONS: Childhood traumatic experiences may be
      associated with prolonged BZD use in opioid-maintained patients and could pose an
      important starting-point for prevention.

PMID- 21715106
TI  - Could a continuous measure of individual transmissible risk be useful in clinical
      assessment of substance use disorder? Findings from the National Epidemiological
      Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: Toward meeting the need for a measure of individual differences in
      substance use disorder (SUD) liability that is grounded in the multifactorial
      model of SUD transmission, this investigation tested to what degree transmissible
      SUD risk is better measured using the continuous Transmissible Liability Index
      (TLI) (young adult version) compared to alternative contemporary clinical
      methods. METHOD: Data from 9535 18- to 30-year-olds in the 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions, a U.S. representative
      sample, were used to compute TLI scores and test hypotheses. Other variables were
      SUDs of each DSM-IV drug class, clinical predictors of SUD treatment outcomes,
      treatment seeking and usage, age of onset of SUDs and substance use (SU), and
      eligibility for SUD clinical trials. RESULTS: TLI scores account for variation in
      SUD risk over and above parental lifetime SUD, conduct and antisocial personality
      disorder criteria and frequency of SU. SUD risk increases two- to four-fold per
      standard deviation increment in TLI scores. The TLI is associated with SUD
      treatment seeking and usage, younger age of onset of SU and SUD, and exclusion
      from traditional clinical trials of SUD treatment. CONCLUSIONS: The TLI can
      identify persons with high versus low transmissible SUD risk, worse prognosis of
      SUD recovery and to whom extant SUD clinical trials results may not generalize.
      Recreating TLI scores in extant datasets facilitates etiology and applied
      research on the full range of transmissible SUD risk in development, treatment
      and recovery without obtaining new samples.

PMID- 21715108
TI  - Suicide attempts and overdoses among adults entering addictions treatment:
      comparing correlates in a U.S. National Study.
AB  - BACKGROUND: Suicide attempts and non-fatal overdoses are both associated with
      substance use. The aim of the present study was to examine correlates of suicide
      attempts and non-fatal overdoses simultaneously among individuals seeking
      addictions treatment. METHODS: A large U.S. national sample of individuals
      entering addictions treatment participated in a cross-sectional survey (n=5892).
      Multinomial logistic regression modeling tested the adjusted associations of
      violence, injection drug use, specific substances, and depressive symptoms with a
      four-category outcome variable based on prior histories of suicide attempt and
      non-fatal overdose (neither, suicide attempt only, overdose only, both),
      adjusting for demographic and treatment characteristics. RESULTS: Sexual and
      physical victimization was associated with suicide attempts with or without
      overdoses (ORs 1.25-2.84), while perpetrating violence was associated with having
      experienced either or both outcomes (ORs 1.25-1.56). Depressive symptoms had a
      stronger association with suicide attempts (OR=3.05) than overdoses (OR=1.29).
      Injection drug use was associated with overdoses with or without suicide attempts
      (ORs 2.65-3.22). Individuals seeking treatment for marijuana use were less likely
      have overdosed or attempted suicide (ORs 0.39-0.67), while individuals seeking
      treatment for heroin use were more likely to have overdosed (OR=1.46). Seeking
      treatment for use of more than one substance was associated with overdose and
      overdose and suicide attempt (ORs 1.58-2.51), but not suicide attempt alone.
      CONCLUSIONS: The present findings indicate that suicide and overdose are
      connected yet distinct problems. Individuals who have had a history of both may
      be a group with particularly poor psychological functioning as well as more
      severe drug-related problems.

PMID- 21715107
TI  - A placebo controlled trial of memantine as an adjunct to oral naltrexone for
      opioid dependence.
AB  - BACKGROUND: Preclinical findings suggest that the inhibition of NMDA
      glutamatergic neurotransmission may have beneficial effects in the treatment of
      opioid dependence. AIMS: We hypothesized that memantine, a low-potency,
      uncompetitive NMDA receptor antagonist, would be safe and effective when used as
      an adjunct to oral naltrexone in the treatment of opioid dependence, particularly
      in preventing relapse to opiate use in detoxified individuals. METHODS: Opioid
      dependent participants (N=112) were enrolled. Following detoxification all
      participants were inducted onto oral naltrexone and were randomized to receive
      memantine 15 mg bid (N=27), memantine 30 mg bid (N=27) or placebo (N=27) for 12
      weeks in combination with naltrexone 50mg/day and individual relapse-prevention
      therapy. The primary outcome was the retention in treatment since treatment
      dropout is most commonly associated with relapse to opiate use. RESULTS: Twenty
      six percent of participants withdrew from treatment prior to starting naltrexone.
      Of those that were randomized 35% completed 4 weeks only, and 24% completed all
      12 weeks of treatment. There was no significant difference in treatment retention
      or heroin use, opiate withdrawal symptoms and craving between the groups treated
      with memantine vs. placebo. CONCLUSION: Thus, the efficacy of memantine 30 or 60
      mg/day as an adjunct to oral naltrexone for the treatment of opiate dependence
      was not supported.

PMID- 21715109
TI  - Salmonella Enteritidis universal stress protein (usp) gene expression is
      stimulated by egg white and supports oviduct colonization and egg contamination
      in laying hens.
AB  - Salmonella enterica subspecies enterica serovar Enteritidis has caused a
      worldwide egg-associated pandemic since the mid 1980s. The exact mechanisms
      causing this egg tropism are still largely unknown, and only a few Salmonella
      genes have been implicated in the interaction with the oviduct or eggs. A in vivo
      expression technology screening performed previously, identified the uspA and
      uspB genes as being highly expressed in the chicken oviduct and in eggs. Here, we
      demonstrate that uspA and uspB gene expression is indeed induced after contact
      with egg white. Intra-oviduct inoculation of Salmonella Enteritidis uspB and
      uspBA mutant strains showed that the mutants had a decreased ability to colonize
      the magnum and isthmus of the oviduct, the organs that produce the egg white and
      eggshell membranes, respectively, at 7 days post-inoculation. Intravenous
      challenge showed that a Salmonella Enteritidis uspBA mutant strain had a
      decreased ability to contaminate eggs. Analogous to the function of universal
      stress proteins A and B in other bacterial species, we hypothesize that the
      Salmonella uspA and uspB genes are involved in long term persistence of
      Salmonella Enteritidis in harmful environments, such as in the oviduct and eggs,
      by conferring resistance against compounds that damage the bacterial cell
      membrane and DNA.

PMID- 21715110
TI  - The cps locus of Streptococcus suis serotype 16: development of a serotype
      specific PCR assay.
AB  - Streptococcus suis serotype 16 can infect pigs and humans. We describe the
      identification and the characterization of the capsular polysaccharides synthesis
      locus of S. suis serotype 16. Using PCR primers flanking the capsular
      polysaccharides synthesis locus, a 30,101-bp fragment was amplified. Twenty-nine
      open reading frames related to transcriptional regulation, glycosyl transfer,
      oligosaccharide repeat unit polymerization, polysaccharide transport, sialic acid
      synthesis and modification were identified. The data suggests that the serotype
      16 capsule is synthesized by a Wzy-dependent pathway. So far, no rapid and
      sensitive diagnostic method is available for detection of serotype 16 isolates. A
      serotype specific PCR test for the rapid and sensitive detection of S. suis
      serotype 16 was developed. Cross hybridization experiments of individual cps
      genes with chromosomal DNAs of 33 serotypes showed that the cps16G and cps16K
      genes hybridized with serotype 16 only. Primers based on cps16G were used to
      develop a serotype 16 specific PCR. The PCR assay was successfully used to
      identify S. suis serotype 16 in the 99 Chinese S. suis clinical isolates and 8
      European isolates.

PMID- 21715111
TI  - The expression of the aryl hydrocarbon receptor in reproductive and
      neuroendocrine tissues during the estrous cycle in the pig.
AB  - The aryl hydrocarbon receptor (AhR) has been recognized as a mediator of
      xenobiotic-induced toxicity. In addition, it was demonstrated that the AhR is
      able to influence the regulation of reproductive processes in females. The aim of
      this study was to examine AhR mRNA (real-time PCR) and protein (Western-blot)
      expression in ovarian follicles and stroma, corpora lutea (CL), oviducts,
      endometrium, myometrium as well as in medial basal hypothalami (MBH), and
      anterior (AP) and posterior (PP) pituitaries harvested during the follicular
      (days 17-19) and luteal (days 8-10) phase of the porcine estrous cycle. The AhR
      transcript and protein were found in all structures collected during both phases.
      AhR mRNA expression tended (p=0.06) to be higher in the CL than in follicles. The
      AhR protein expression in ovarian stroma was higher (p<=0.01) during the
      follicular than in the luteal phase. Endometrial expression of AhR mRNA was
      higher (p<=0.01), while AhR protein was lower (p<=0.01) during the follicular
      phase in comparison to the luteal phase. Within neuroendocrine tissues, AhR mRNA
      and protein content in hypothalamus were relatively low and did not differ
      (p>0.05) between phases. In contrast, higher AhR mRNA expression in AP (p<=0.001)
      and protein expression in PP (p<=0.01) were found during the luteal phase
      compared to the follicular phase. Differences in AhR expression observed in
      reproductive and neuroendocrine tissues during the follicular and luteal phase of
      the estrous cycle indicate the involvement of AhR in the regulation of
      reproductive function in pigs.

PMID- 21715112
TI  - Age and sex related measurement of craniofacial soft tissue thickness and nasal
      profile in the Chinese population.
AB  - The purpose of this study was to acquire accurate data of craniofacial soft
      tissue thickness (CFSTT) and nasal profile in Chinese people of Han population. A
      total of 31 anatomical landmarks and 4 nasal profile parameters were determined
      using magnetic resonance imaging (MRI) in 425 subjects (233 males and 192
      females). In the present study, the mean CFSTT values of male subjects exceeded
      those of female subjects at most anatomical landmarks except at seven (22.58%)
      and 6 out of the 7 landmarks were bilateral anatomical landmark points. The age
      related and sex * age interactions were found to be statistically significant at
      all landmarks. Significant differences were found in the nasal profile data of
      males and females, and 15 out of 20 different groups had significant differences
      between sexes, and the mean values of nasal length, nasal height, nasal depth and
      nasal breadth in males were all greater than those in females. Furthermore, both
      CFSTT and nasal profile showed good correlation with age. The thickest CFSTT of
      male and female were found at the respective ages of 45-59 and 35-44, and the
      nasal profile becomes more constant after 24 years of age. CFSTT of the lower
      part of the face shows greater variation compared to the upper part, so special
      care needs to be applied when reconstructing the lower portion of the face. Our
      data on CFSTT and nasal profile for the Chinese Xi'an Han population is important
      in understanding craniofacial characteristics of the Chinese population and might
      be potentially helpful in forensic identification.

PMID- 21715113
TI  - Estimating the pre-appearance interval from temperature in Necrodes littoralis L.
      (Coleoptera: Silphidae).
AB  - While estimating post-mortem interval from entomological evidence it is useful to
      divide it into two separate intervals: the pre-appearance interval (PAI) and the
      development interval in the case of immature insects and PAI and the presence
      interval in the case of adult insects. An accurate estimate of PAI is critically
      important particularly in the case of those insects which appear on remains late
      in decomposition. In this paper the possibilities of PAI estimation from
      temperature are evaluated in late-arriving, forensically important carrion beetle
      Necrodes littoralis. The relationship between PAI of adult and larval N.
      littoralis and temperature was modelled by using results of succession
      experiments in forests of Central Europe. In both stages PAI was found to be
      strongly, inversely dependent on mean daily ground level temperatures averaged
      for the duration of PAI. Several methods of PAI estimation were proposed and
      their accuracy was initially evaluated with external successional data.

PMID- 21715114
TI  - MR findings of ruptured endometrial cyst: comparison with tubo-ovarian abscess.
AB  - OBJECTIVE: To evaluate the MR findings of ruptured endometrial cyst, focusing on
      the differentiation from tubo-ovarian abscess (TOA). PATIENTS AND METHODS: We
      reviewed the records of 21 patients who underwent preoperative MR examinations
      for TOAs (n=15) or ruptured endometrial cysts (n=6). We evaluated the presence of
      hyper-intense ascites and hyper-intense peritoneum in T1-weighted sequences,
      strong enhancement of the peritoneum, hyper-intense content and hyper-intense rim
      of the ovarian lesion in T1-weighted sequences, and strong wall enhancement of
      the ovarian lesion. chi2 test was used to assess the relationship between TOA
      cases versus cases with ruptured endometrial cysts, and the three MR peritoneal
      findings. We evaluated the relationship between TOA versus non-infected
      endometrial cysts, and the ovarian MR peritoneal findings, too. RESULTS: Hyper
      intense ascites was found in all of the patients with ruptured endometrial cyst
      and none with TOA (p<0.0001). Hyper-intense peritoneum was observed in only TOAs
      cases (4 of 8). Strong peritoneal enhancement was seen in 3 of the 3 patients
      with ruptured endometrial cyst and 7 of the 13 patients with TOA (p=0.1366).
      Hyper-intense content of the ovarian lesion was seen more often in the non
      infected endometrial cysts than in the TOAs (p=0.001607), while hyper-intense rim
      was more frequent in TOAs (p=0.000402). Strong wall enhancement was observed only
      in TOAs (11 of 15) (p=0.001355). CONCLUSIONS: MR images are useful to
      differentiate ruptured endometrial cyst from TOA.

PMID- 21715115
TI  - Image quality of mammography in Croatian nationwide screening program: comparison
      between various types of facilities.
AB  - PURPOSE: The study was aimed to provide objective evidence about the mammographic
      image quality in Croatia, to compare it between different types of MG facilities
      and to identify the most common deficiencies and possible reasons as well as the
      steps needed to improve image quality. MATERIALS AND METHODS: A total of 420
      mammographic examinations collected from 84 mammographic units participating in
      the Croatian nationwide breast cancer screening program were reviewed in terms of
      four image quality categories: identification of patient and examination, breast
      positioning and compression, exposure and contrast, and artifacts. Those were
      rated using image evaluating system based on American College of Radiology and
      European Commission proposals. The results were compared among different types of
      mammographic units, and common image quality deficiencies were identified.
      RESULTS: Total image quality scores of 12.8, 16.1, 13.0 and 13.7 were found for
      general hospitals, university hospitals, private clinics and public healthcare
      centres, respectively. Average score for all mammographic units was 13.5 (out of
      25 points). University hospitals were significantly better than all other
      mammography units in overall image quality, which was mostly contributed by
      better breast positioning practices. Private clinics showed the worst results in
      identification, exposure, contrast and artifacts. CONCLUSIONS: Serious
      deficiencies in identification and breast positioning, which might compromise
      breast cancer screening outcome, were detected in our material. They occur mainly
      due to subjective reasons and could be corrected through additional staff
      training and improvement of working discipline.

PMID- 21715116
TI  - Situs anomalies on prenatal MRI.
AB  - OBJECTIVE: Situs anomalies refer to an abnormal organ arrangement, which may be
      associated with severe errors of development. Due regard being given to prenatal
      magnetic resonance imaging (MRI) as an adjunct to ultrasonography (US), this
      study sought to demonstrate the in utero visualization of situs anomalies on MRI,
      compared to US. MATERIALS AND METHODS: This retrospective study included 12
      fetuses with situs anomalies depicted on fetal MRI using prenatal US as a
      comparison modality. With an MRI standard protocol, the whole fetus was assessed
      for anomalies, with regard to the position and morphology of the following
      structures: heart; venous drainage and aorta; stomach and intestines; liver and
      gallbladder; and the presence and number of spleens. RESULTS: Situs inversus
      totalis was found in 3/12 fetuses; situs inversus with levocardia in 1/12
      fetuses; situs inversus abdominis in 2/12 fetuses; situs ambiguous with
      polysplenia in 3/12 fetuses, and with asplenia in 2/12 fetuses; and isolated
      dextrocardia in 1/12 fetuses. Congenital heart defects (CHDs), vascular
      anomalies, and intestinal malrotations were the most frequent associated
      malformations. In 5/12 cases, the US and MRI diagnoses were concordant. Compared
      to US, in 7/12 cases, additional MRI findings specified the situs anomaly, but
      CHDs were only partially visualized in six cases. CONCLUSIONS: Our initial MRI
      results demonstrate the visualization of situs anomalies and associated
      malformations in utero, which may provide important information for perinatal
      management. Using a standard protocol, MRI may identify additional findings,
      compared to US, which confirm and specify the situs anomaly, but, with limited
      MRI visualization of fetal CHDs.

PMID- 21715117
TI  - Preoperative assessment of longitudinal extent of bile duct cancers using MDCT
      with multiplanar reconstruction and minimum intensity projections: comparison
      with MR cholangiography.
AB  - OBJECTIVE: To compare the performance of MDCT, including multiplanar reformation
      (MPR) and minimum intensity projection (MinIP) images, with that of transaxial
      MDCT with MR cholangiography (MRC) in the preoperative evaluation of the
      longitudinal extent of bile duct cancer. METHODS: Twenty-seven patients with
      surgically proven bile duct cancer, who had undergone preoperative multiphasic
      MDCT and MRC, were included. Two radiologists evaluated the MDCT set with MPR and
      MinIP images and the image set of transaxial MDCT with MRC, regarding the
      longitudinal extent of bile duct cancer. The results were compared with the
      surgical and pathology findings. RESULTS: The area under the receiver operating
      characteristic curves of the MDCT set with MPR and MinIP images and the image set
      of transaxial MDCT with MRC for predicting the longitudinal extent of bile duct
      cancer, were 0.938, 0.923 and 0.839, 0.836 for both reviewers. The differences
      were not statistically significant for either image set or either reviewer. The
      sensitivity and specificity of the MDCT image set for detecting tumor involvement
      of the biliary second confluences or intrapancreatic segment were similar for
      both reviewers to those of transaxial MDCT with MRC. CONCLUSIONS: MDCT with MPR
      and MinIP images showed comparable diagnostic performance to that of transaxial
      MDCT with MRC for predicting the longitudinal extent of bile duct cancer.

PMID- 21715118
TI  - On primary pulmonary amyloidosis.

PMID- 21715119
TI  - Characterization and determination of the major constituents in Belamcandae
      Rhizoma by HPLC-DAD-ESI-MS(n).
AB  - Belamcandae Rhizoma, derived from the rhizome of Belamcanda chinensis (L.) DC.,
      has been used as traditional Chinese medicine for the treatment of coughing and
      pharyngitis. However, there have been few studies dealing with the systematic
      analysis of the bioactive constituents in Belamcandae Rhizoma. In this work, high
      performance liquid chromatography-diode array detection-electrospray ionization
      multiple-stage mass spectrometry (HPLC-DAD-ESI-MS(n)) combined with liquid
      chromatography-time of flight-mass spectrometry (HPLC-TOF/MS) was established for
      profiling and characterization of multi-constituent in Belamcandae Rhizoma. The
      ESI-MS(n) fragmentation behaviors of the authentic references were proposed for
      aiding the structural identification of components in the extract. Thirty-five
      flavonoids, including 30 isoflavones and five xanthones, were identified or
      tentatively identified by comparing their retention times, UV and MS spectra with
      those of authentic compounds or literature data. Twelve of the identified
      compounds (neomangiferin, mangiferin, tectoridin, iristectorin B, iristectorin A,
      iridin, tectorigenin, iristectorigenin A, irigenin, irisflorentin, irilone and
      dichtomitin) were determined by HPLC-DAD using a C(18) column. The results
      indicated that the developed analysis method could be employed as a rapid,
      effective technique for structural characterization of chemical constituents in
      herbal medicine. This work is expected to provide comprehensive information for
      the quality evaluation of Belamcandae Rhizoma, which would be a valuable
      reference for the further study and development of this herb and related
      medicinal products.

PMID- 21715120
TI  - Determination of nucleoside analog mono-, di-, and tri-phosphates in cellular
      matrix by solid phase extraction and ultra-sensitive LC-MS/MS detection.
AB  - An ultra-sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS)
      assay was developed and validated to facilitate the assessment of clinical
      pharmacokinetics of nucleotide analogs from lysed intracellular matrix. The
      method utilized a strong anion exchange isolation of mono-(MP), di-(DP), and tri
      phosphates (TP) from intracellular matrix. Each fraction was then
      dephosphorylated to the parent moiety yielding a molar equivalent to the original
      nucleotide analog intracellular concentration. The analytical portion of the
      methodology was optimized in specific nucleoside analog centric modes (i.e.
      tenofovir (TFV) centric, zidovudine (ZDV) centric), which included
      desalting/concentration by solid phase extraction and detection by LC-MS/MS.
      Nucleotide analog MP-, DP-, and TP-determined on the TFV centric mode of analysis
      include TFV, lamivudine (3TC), and emtricitibine (FTC). The quantifiable linear
      range for TFV was 2.5-2000 fmol/sample, and that for 3TC/FTC was 0.1 200
      pmol/sample. Nucleoside analog MP-, DP-, and TP-determined on the ZDV centric
      mode of analysis included 3TC and ZDV. The quantifiable linear range for 3TC was
      0.1 100 pmol/sample, and 5-2000 fmol/sample for ZDV. Stable labeled isotopic
      internal standards facilitated accuracy and precision in alternative cell
      matrices, which supported the intended use of the method for MP, DP, and TP
      determinations in various cell types. The method was successfully applied to
      clinical research samples generating novel intracellular information for TFV,
      FTC, ZDV, and 3TC nucleotides. This document outlines method development,
      validation, and application to clinical research.

PMID- 21715121
TI  - Detection of counterfeit Viagra(r) by Raman microspectroscopy imaging and
      multivariate analysis.
AB  - During the past years, pharmaceutical counterfeiting was mainly a problem of
      developing countries with weak enforcement and inspection programs. However,
      Europe and North America are more and more confronted with the counterfeiting
      problem. During this study, 26 counterfeits and imitations of Viagra(r) tablets
      and 8 genuine tablets of Viagra(r) were analysed by Raman microspectroscopy
      imaging. After unfolding the data, three maps are combined per sample and a first
      PCA is realised on these data. Then, the first principal components of each
      sample are assembled. The exploratory and classification analysis are performed
      on that matrix. PCA was applied as exploratory analysis tool on different
      spectral ranges to detect counterfeit medicines based on the full spectra (200
      1800 cm-1), the presence of lactose (830-880 cm-1) and the spatial distribution
      of sildenafil (1200-1290 cm-1) inside the tablet. After the exploratory analysis,
      three different classification algorithms were applied on the full spectra
      dataset: linear discriminant analysis, k-nearest neighbour and soft independent
      modelling of class analogy. PCA analysis of the 830-880 cm-1 spectral region
      discriminated genuine samples while the multivariate analysis of the spectral
      region between 1200 cm-1 and 1290 cm-1 returns no satisfactory results. A good
      discrimination of genuine samples was obtained with multivariate analysis of the
      full spectra region (200-1800 cm-1). Application of the k-NN and SIMCA algorithm
      returned 100% correct classification during both internal and external
      validation.

PMID- 21715122
TI  - Transcatheter valve therapy a professional society overview from the american
      college of cardiology foundation and the society of thoracic surgeons.

PMID- 21715123
TI  - The importance of a proper against-medical-advice (AMA) discharge: how signing
      out AMA may create significant liability protection for providers.
AB  - BACKGROUND: Every year, patients leave the Emergency Department against medical
      advice (AMA) and before an adequate evaluation can be performed. It is well known
      that many of these patients are at risk of subsequent complications. OBJECTIVE:
      The goal of this article is to explain the potential legal protections that may
      be created from a proper AMA discharge. DISCUSSION: In this article, the authors
      review the steps that need to be taken when performing an AMA discharge,
      including an assessment of capacity, proper documentation, and adequate
      disclosure. The authors then review the potential legal protections that can
      result from a properly documented and performed discharge. Among these
      protections are: proof that the provider's duty to the patient ended with
      discharge and that the patient assumed the risk of a subsequent complication.
      CONCLUSION: The authors conclude that a properly executed discharge can provide
      significant legal protection from liability risks.

PMID- 21715124
TI  - The effect of an education programme (MEDIAS 2 ICT) involving intensive insulin
      treatment for people with type 2 diabetes.
AB  - OBJECTIVE: In a randomized, multi-centre trial, the effect of an education
      programme (MEDIAS 2 ICT) involving intensive insulin treatment for people with
      type 2 diabetes was compared with an established education programme as an active
      comparator condition (ACC). METHODS: We investigated whether MEDIAS 2 ICT was non
      inferior to ACC in overall glycaemic control. Secondary outcomes were the
      diabetes-related distress, diabetes knowledge, quality of life, self-care
      behavior, lipids, blood pressure and weight. RESULTS: 186 subjects were
      randomized. After a six month follow-up the mean HbA1c decrease was 0.37% (from
      8.2+/-1.1% to 7.8+/-1.5%) in the ACC and 0.63% (from 8.5+/-1.5% to 7.9+/-1.2%) in
      MEDIAS 2 ICT. The mean difference between both groups was -0.26% (95% CI -0.63 to
      -0.14) in favor of MEDIAS 2 ICT. This result was within the predefined limit for
      non-inferiority. Diabetes-related distress was significantly more reduced in
      MEDIAS 2 ICT (-3.4+/-7.1) than in ACC (0.4+/-9.0; p=0.31). CONCLUSION: MEDIAS 2
      ICT is as effective in lowering HbA1c as previously established education
      programmes, but showed superiority in reducing diabetes-related distress.
      PRACTICAL IMPLICATIONS: MEDIAS 2 ICT provides an alternative for education of
      people with type 2 diabetes treated by multiple injection therapy.

PMID- 21715125
TI  - The interaction order and clinical practice: Some observations on dysfunctions
      and action steps.
AB  - OBJECTIVE: This paper examines three dysfunctional communication processes in the
      primary care consultation using conversation analysis theory and methods:
      dysfunctions in problem presentation, medical questioning that limits the
      expression of additional concerns, and the emergence of discordance between
      physicians and patients in the context of treatment recommendations. RESULTS: It
      is proposed that these dysfunctions arise from the transfer of normative
      conventions that function well in the practice of ordinary conversation into
      medical contexts where they serve to limit the effectiveness of communication.
      Because these conventions are rooted in, and reinforced by, the activities of
      daily life, they may be difficult to eradicate from the medical visit. PRACTICE
      IMPLICATIONS: Reduction of these dysfunctions is most likely to emerge when
      physicians recognize the nature of these dysfunctional practices and their roots
      in everyday social life. Recognition of these practices together with their
      functions and dysfunctions may hold a solid prospect for improvements in medical
      communication.

PMID- 21715126
TI  - Acute aortic occlusion with sudden paraplegia secondary to Aspergillus niger
      embolism from Aspergillus niger aortitis.
AB  - Acute aortic occlusion caused by a saddle embolus is a rare vascular emergency.
      Associated sudden paraplegia secondary to spinal cord ischemia is even more
      uncommon. Aspergillus surgical site infection is typically linked to cardiac
      surgery but is exceptional. Here we present a case that combines all of these
      factors. A 67-year-old man presented with sudden paraplegia from acute aortic
      occlusion with a saddle embolus from Aspergillus niger aortitis 4 months after
      aortic valve replacement and aortoplasty. We believe this to be the second
      reported case of Aspergillus niger aortitis and the first presenting as aortic
      occlusion with paraplegia.

PMID- 21715127
TI  - Successful endovascular treatment of hemosuccus pancreaticus due to splenic
      artery aneurysm associated with segmental arterial mediolysis.
AB  - Hemosuccus pancreaticus, which is generally due to the rupture of a splenic
      artery aneursym into the pancreatic duct, is a rare cause of intermittent upper
      gastrointestinal hemorrhage. Segmental arterial mediolysis (SAM) is a rare
      arteriopathy. We report a 53-year-old man with hemosuccus pancreaticus due to a
      splenic artery aneurysm associated with SAM. The patient, who also had a celiac
      artery aneurysm affected by SAM, was successfully treated by both coil
      embolization and aortic stent grafting for complete coverage of the celiac
      artery. SAM is a very rare cause of hemosuccus pancreaticus, and endovascular
      treatment may be favorable for hemosuccus pancreaticus.

PMID- 21715128
TI  - Correlation between TBARS levels and glycolytic enzymes: the importance to the
      initial evaluation of clinical outcome of colorectal cancer patients.
AB  - Colorectal cancer (CRC) has been associated with high levels of lipid
      peroxidation, probably due to neoplasic tissue metabolism. Our objectives were to
      relate lipid peroxidation with the evolution of CRC and with various biomarkers
      (GGT, ALP, LDH, CEA) to assess its prognostic value. A longitudinal study was
      conducted with CRC patients (n=43), using FOLFOX4. At the end of the treatment,
      patients were grouped into two groups: poor outcome (PO) for those patients whose
      computed tomography showed signs of metastasis, not reduced or increased in the
      previous implants, and not reduced or increased in CEA levels and good outcome
      (GO) for the opposite trends. PO patients had a significant increase in TBARS
      levels, being different from other group in cycles 4, 5, and 6 of chemotherapy.
      After cycle 6 of chemotherapy, GO patients had higher SOD (27%) and catalase
      (33%) activity. TBARS levels showed a positive correlation with biomarkers at the
      beginning of the treatment, which disappeared after six cycles of chemotherapy,
      when TBARS levels of the PO group started to increase; the other parameters
      increased at a later time. Because the serum TBARS levels in GO patients did not
      increase after the beginning of chemotherapy, it is expected that the increase is
      not a result of the effects of chemotherapy but of sickness evolution. It is
      possible that the systemic assessment of lipid peroxidation might become an
      additional marker because it occurs earlier than other biomarkers and could
      therefore be useful in the prognosis of CRC patients.

PMID- 21715129
TI  - Overcoming multidrug resistance (MDR) in cancer in vitro and in vivo by a
      quinoline derivative.
AB  - Multidrug resistance (MDR) mediated by the over expression of drug efflux protein
      P-glycoprotein (P-gp) is one of the major impediments to successful treatment of
      cancer. P-gp acts as an energy-dependent drug efflux pump and reduces the
      intracellular concentration of structurally unrelated drugs inside the cells.
      Therefore, there is an urgent need for development of new compound that are less
      toxic and effective against drug resistance in cancer. Preclinical studies have
      shown that quinoline derivatives possess anticancer activities. Here, we report
      the antitumor potential of quinoline derivative, 2-(2-Methyl-quinolin-4ylamino)-N
      phenyl acetamide (S4). To evaluate the cytotoxic potential of S4, we used four
      different cell lines (Hela, HCT-116, CCRF-CEM, and CEM/ADR 5000) in vitro, and
      showed that S4 kills doxorubicin resistant T lymphoblastic leukemia cell, CEM/ADR
      5000 in a concentration dependent manner while others remains unaffected.
      Moreover, S4 induces apoptosis in CEM/ADR 5000 cells through generation reactive
      oxygen species (ROS). This is substantiated by the fact that the antioxidant N
      acetyle-cysteine (NAC) completely blocks ROS generation and, subsequently,
      abrogates S4 induced apoptosis. Furthermore, in vivo treatment with S4
      significantly increases the life span of swiss albino mice bearing sensitive and
      doxorubicin resistant subline of Ehrlich ascites carcinoma. In addition,
      intraperitoneal application of S4 in mice does not show any systemic toxicity at
      concentrations that in preliminary trials in a mice Ehrlich ascites carcinoma
      model. Therefore, present report provides evidence that S4, a quinoline
      derivative, may be a promising new therapeutic agent against drug resistant
      cancers.

PMID- 21715130
TI  - A review on various heterocyclic moieties and their antitubercular activity.
AB  - Tuberculosis (TB), a contagious infection caused by Mycobacterium tuberculosis,
      still remains the leading cause of the worldwide death among the infectious
      disease. Different moieties like pyrazoline, benzimidazol, purines, thiazole,
      flouroquinolones, quinoxaline, oxadiazol, pyrazol, thiozolidinones and
      azetidinones have been studied, synthesized and evaluated worldwide against M.
      tuberculosis to show their antitubercular activity.

PMID- 21715131
TI  - Cardiac magnetic resonance imaging and ischaemic cardiomyopathies: what are the
      indications?
AB  - Cardiac magnetic resonance imaging (CMR) has much to offer to clinicians caring
      for patients with ischaemic heart disease. This article describes briefly the
      basic principles and practical aspects of cardiac magnetic resonance imaging, and
      summarises the pathophysiology of ischaemic heart disease. Then, it discusses in
      detail the use of CMR for detection of coronary artery disease, and for
      assessment of acute and stable coronary syndromes.

PMID- 21715132
TI  - Acute kidney injury on ventilator initiation day independently predicts prolonged
      mechanical ventilation in intensive care unit patients.
AB  - PURPOSE: The purpose of this study is to identify the predictors for prolonged
      mechanical ventilation (PMV) of more than 21 days among intensive care unit (ICU)
      patients. MATERIAL AND METHODS: A retrospective observational study was conducted
      in a respiratory ICU from December 2008 to November 2009. The outcome measurement
      was the occurrence of PMV. Acute kidney injury (AKI) was identified and defined
      as an increase in the serum creatinine level of 50% or greater from baseline.
      RESULTS: Of 154 patients enrolled, 41 patients (26.6%) had PMV. Patients with PMV
      showed higher Acute Physiology and Chronic Health Evaluation II scores, lower
      serum albumin levels, and more AKI on mechanical ventilation (MV) initiation day
      compared with the non-PMV patients. Patients with PMV were significantly
      associated with longer MV duration before the day of readiness for weaning (DRW)
      and a higher rapid shallow breathing index on DRW. In a multivariate regression
      analysis, the independent risk factors for PMV were AKI on MV initiation day
      (odds ratio [OR], 5.630; 95% confidence interval [CI], 1.378-22.994; P = .016),
      longer MV duration before DRW (OR, 1.289; 95% CI, 1.158-1.435; P < .001), and
      higher rapid shallow breathing index on DRW (OR, 1.012; 95% CI, 1.003-1.021; P =
      .010). CONCLUSIONS: Acute kidney injury on MV initiation day is an independent
      risk factor for PMV of more than 21 days, which may be helpful for clinicians to
      refine their management of these ICU patients early.

PMID- 21715133
TI  - High-frequency oscillatory ventilation in patients with acute exacerbation of
      chronic obstructive pulmonary disease.
AB  - PURPOSE: High-frequency oscillatory ventilation (HFOV) is usually considered not
      indicated for treatment of patients with chronic obstructive pulmonary disease
      (COPD) because of the theoretical risk of air trapping and hyperinflation. The
      aim of our study was to establish whether HFOV can be safely applied in patients
      with acute exacerbation of COPD and hypercapnic respiratory failure. METHODS: Ten
      patients (age, 63-83 years) requiring intensive care treatment who failed on
      noninvasive ventilation were studied. After initial conventional mechanical
      ventilation (CMV) of less than 72 hours, all patients were transferred to HFOV
      for 24 hours and then back to CMV. Arterial blood gases, spirometry, and
      hemodynamic parameters were repeatedly obtained in all phases of CMV and HFOV at
      different settings. Regional lung aeration and ventilation were assessed by
      electrical impedance tomography. RESULTS: High-frequency oscillatory ventilation
      was tolerated well; no adverse effects or severe hyperinflation and hemodynamic
      compromise were observed. Effective CO(2) elimination and oxygenation were
      achieved. Ventilation was more homogeneously distributed during HFOV than during
      initial CMV. Higher respiratory system compliance and tidal volume were found
      during CMV after 24 hours of HFOV. CONCLUSIONS: Our study indicates that short
      term HFOV, using lower mean airway pressures than recommended for acute
      respiratory distress syndrome, appears safe in patients with COPD while securing
      adequate pulmonary gas exchange.

PMID- 21715134
TI  - Health-care system distrust in the intensive care unit.
AB  - PURPOSE: To examine the performance and properties of the Revised Health Care
      System Distrust Scale among surrogates in the intensive care unit (ICU).
      MATERIALS AND METHODS: Pilot, prospective cohort study of 50 surrogates of adult,
      mechanically ventilated patients surveyed on days 1, 3, and 7 of ICU admission.
      RESULTS: Responses on the Health Care System Distrust Scale on day 1 ranged from
      9 to 34 (possible range 9-45, with higher scores indicating more distrust), with
      a mean and SD of 20.3 +/- 6.9. Factor analysis demonstrated a 2-factor structure,
      corresponding to the domains of values and competence. Cronbach alpha for the
      overall scale was .83, for the competence subscale, .76, and for the values
      subscale, .74. Health-care system distrust was inversely correlated with trust in
      ICU physicians (Pearson coefficient -.63). When evaluated over the course of each
      patient's ICU stay, health-care system distrust ratings decreased by 0.31 per
      patient-day (95% CI 0.55-0.06, P = .015). Correlation between health-care system
      distrust and trust in ICU physicians decreased slightly over time. CONCLUSIONS:
      Among surrogates in the ICU, the Health Care System Distrust Scale has high
      internal consistency and convergent validity. There was substantial variability
      in surrogates' trust in the health-care system.

PMID- 21715135
TI  - Analysis of progression in risk, injury, failure, loss, and end-stage renal
      disease classification on outcome in patients with severe sepsis and septic
      shock.
AB  - INTRODUCTION: A few studies have assessed risk, injury, failure, loss, and end
      stage renal disease (RIFLE) criteria in patients with severe sepsis and septic
      shock, a setting in which acute kidney injury (AKI) is common and dramatically
      worsens outcome. METHODS: Study subjects included all consecutive patients with
      severe sepsis and septic shock who had been admitted to the medical intensive
      care unit between January 2005 and December 2006. RESULTS: Of 326 patients
      admitted during the study period, 291 were included. According to RIFLE criteria,
      204 patients (70.1%) had AKI (risk, 26.1%; injury, 26.5%; failure, 17.5%) on
      admission. Overall, 28-day mortality rate was 48.5%. Mortality was not associated
      with admission RIFLE (risk, 44.7%; injury, 53.2%; failure, 51.0%; P = .58).
      However, maximum RIFLE was associated with increased 28-day mortality (P < .01).
      After adjustment for age, sex, Acute Physiology and Chronic Health Evaluation II
      score, and Sequential Organ Failure Assessment score, independent risk factors
      for 28-day mortality were newly developed AKI (odds ratio [OR], 11.4; P < .01),
      progression of RIFLE risk to higher RIFLE class (OR, 14.5; P < .01), maximum
      RIFLE injury (OR, 5.58; P < .01), and maximum RIFLE failure (OR, 7.64; P < .01).
      CONCLUSIONS: Progression of RIFLE class and newly developed AKI after hospital
      admission were better able to predict 28-day mortality than RIFLE criteria on the
      first day of admission in patients with severe sepsis and septic shock.

PMID- 21715136
TI  - Acinetobacter baumannii infection in patients with hematologic malignancies in
      intensive care unit: risk factors and impact on mortality.
AB  - PURPOSE: We investigated the characteristics of Acinetobacter baumannii infection
      in critically ill patients with hematologic malignancies. MATERIALS AND METHODS:
      The prospectively collected data of patients with hematologic malignancies
      admitted to a medical intensive care unit of a university hospital from 2007
      through 2010 were reviewed retrospectively. RESULTS: One hundred twenty-eight
      patients were included in the study, among whom 35 (27%) developed 39 A baumannii
      infections. Pneumonia was the most common infection site of A baumannii. Presence
      of neutropenia, underlying hematologic malignancy, and the disease status did not
      affect the acquisition of the infection. Advancing age, prior exposure to
      aminoglycosides, central venous catheterization, and presence of nasogastric tube
      were the independent risk factors for the development of A baumannii infections.
      The mortality rate was higher in patients with A baumannii infections compared
      with the ones without (P = .009). However, in multivariate analysis, low Glasgow
      coma scale, prior immunosuppressive treatment, neutropenia, invasive mechanical
      ventilation, and severe sepsis were independently associated with mortality,
      whereas presence of A baumannii infection was not. CONCLUSIONS: Despite the high
      mortality rate in critically ill patients with hematologic malignancies, presence
      of A baumannii infection was not an independent risk factor for mortality.

PMID- 21715137
TI  - Is disclosing conflicts of interest like purifying in the Ganges river?

PMID- 21715138
TI  - Lung-protective mechanical ventilation does not protect against acute kidney
      injury in patients without lung injury at onset of mechanical ventilation.
AB  - INTRODUCTION: Preclinical and clinical studies suggest that mechanical
      ventilation contributes to the development of acute kidney injury (AKI),
      particularly in the setting of lung-injurious ventilator strategies. OBJECTIVE:
      To determine whether ventilator settings in critically ill patients without acute
      lung injury (ALI) at onset of mechanical ventilation affect the development of
      AKI. DESIGN, SETTING, AND PATIENTS: Secondary analysis of a randomized controlled
      trial (N = 150), comparing conventional tidal volume (V(T), 10 mL/kg) with low
      tidal volume (V(T), 6 mL/kg) mechanical ventilation in critically ill patients
      without ALI at randomization. During the first 5 days of mechanical ventilation,
      the RIFLE class was determined daily, whereas neutrophil gelatinase-associated
      lipocalin and cystatin C levels were measured in plasma collected on days 0, 2,
      and 4. RESULTS: Eighty-six patients had no AKI at inclusion, and 18 patients
      (21%) subsequently developed AKI, but without significant difference between
      ventilation strategies. (Cumulative hazard, 0.26 vs 0.23; P = .88.) The courses
      of neutrophil gelatinase-associated lipocalin and cystatin C plasma levels did
      not differ significantly between randomization groups. CONCLUSION: In the present
      study in critically patients without ALI at onset of mechanical ventilation,
      lower tidal volume ventilation did not reduce the development or worsening of AKI
      compared with conventional tidal volume ventilation.

PMID- 21715139
TI  - Muscle weakness in septic patients requiring mechanical ventilation: protective
      effect of transcutaneous neuromuscular electrical stimulation.
AB  - PURPOSE: The aim of this study was to evaluate the effect of transcutaneous
      neuromuscular electrical stimulation (NMES) on muscle strength in septic patients
      requiring mechanical ventilation (MV). METHODS: Sixteen septic patients requiring
      MV and having 1 or more organ failure other than respiratory dysfunction were
      enrolled within 48 hours from admission to the intensive care unit. Neuromuscular
      electrical stimulation was administered twice a day on brachial biceps and vastus
      medialis (quadriceps) of 1 side of the body until MV withdrawal. Blinded
      investigators measured arm and thigh circumferences, biceps thickness by
      ultrasonography, and muscle strength after awakening with Medical Research
      Council scale. RESULTS: Two patients died before strength evaluation and were
      excluded from the analysis. Neuromuscular electrical stimulation was applied for
      13 days (interquartile range, 7-30 days). Biceps (P = .005) and quadriceps (P =
      .034) strengths were significantly higher on the stimulated side at the last day
      of NMES. Improvement was mainly observed in more severe and weaker patients.
      Circumference of the nonstimulated arm decreased at the last day of NMES (P =
      .015), whereas no other significant differences in limb circumferences or biceps
      thickness were observed. CONCLUSION: Neuromuscular electrical stimulation was
      associated with an increase in strength of the stimulated muscle in septic
      patients requiring MV. Neuromuscular electrical stimulation may be useful to
      prevent muscle weakness in this population.

PMID- 21715140
TI  - The use of an electronic medical record based automatic calculation tool to
      quantify risk of unplanned readmission to the intensive care unit: a validation
      study.
AB  - OBJECTIVE: The aim of this study was to refine and validate an automatic risk of
      unplanned readmission (Stability and Workload Index for Transfer, or SWIFT)
      calculator in a prospective cohort of consecutive medical intensive care unit
      (ICU) patients in a teaching hospital with comprehensive electronic medical
      records (EMRs). DESIGN: A 2-phase (derivation and validation) prospective cohort
      study was conducted. SETTINGS: The study was conducted in an academic medical
      ICU. SUBJECTS: A consecutive cohort of adult (age >18 years) patients with
      research authorization were analyzed. INTERVENTION: The EMR-based automatic SWIFT
      calculator was used for this study. MEASUREMENT: Agreement between the manual
      ("gold standard") and automatic SWIFT calculation tool was obtained. MAIN
      RESULTS: During the derivation phase, we enrolled 191 consecutive medical ICU
      patients. Scores of SWIFT for these patients calculated manually by the 2
      reviewers had strong positive correlation (r = 0.97), and the mean (SD)
      difference was 0.43 (3.5). The first iteration of the automatic SWIFT calculator
      in the derivation cohort demonstrated excellent agreement with manual
      calculation, partial pressure of carbon dioxide in arterial blood (kappa = 0.95),
      partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio
      (kappa = 0.69), length of ICU stay (kappa = 0.91), and Glasgow comma scale (kappa
      = 0.90) and no agreement for source of ICU admission (kappa = -0.15). After
      adjustment in rules, the kappa value for hospital admission source improved to
      1.0. Automatic calculation demonstrated strong correlation with manual (r =
      0.92), and mean (SD) difference was -2.3 (5.9). During validation phase, 100
      subjects were enrolled at 5 days. The automatic tool retained excellent
      correlation with gold-standard calculation for SWIFT (r = 0.92), and the mean
      (SD) difference was -2.2 (5.5). CONCLUSION: The EMR-based automatic tool
      accurately calculates SWIFT score and can facilitate ICU discharge decisions
      without the need for manual data collection.

PMID- 21715141
TI  - The effect of intensive bimanual training on coordination of the hands in
      children with congenital hemiplegia.
AB  - Recent studies have suggested efficacy of intensive bimanual training in
      improving the quality and quantity of affected hand use in children with
      hemiplegia. However, it is not known whether such training affects the
      coordination of the two hands. In the present study, 20 children with congenital
      hemiplegia (age 4-10 years; MACS levels I-II) were randomly assigned to either an
      intensive bimanual training (Hand-Arm Bimanual Intensive Therapy: HABIT) group,
      or a control group consisting of equally intensive unimanual treatment
      (Constraint-Induced Movement Therapy, CIMT) for 6h per day for 15 days (90h). To
      assess their bimanual coordination, children were asked to open a drawer with one
      hand and manipulate its contents with the other hand. 3-D movement kinematics
      were recorded and subsequently analyzed by a blind evaluator. The role of the two
      hands was varied. Following treatment, superior improvement in bimanual
      coordination was found for the bimanual training group as indicated by greater
      movement overlap (the percentage of time with both hands engaged in the task p =
      0.047) and better goal synchronization (reduced time differences between the two
      hands completing the task goals, p = 0.005). The results suggest that bimanual
      training improves the spatial-temporal control of the two hands, and are in
      agreement with the principle of practice specificity.

PMID- 21715142
TI  - Speech perception in noise deficits in Japanese children with reading
      difficulties: effects of presentation rate.
AB  - We examined the effects of presentation rate on speech perception in noise and
      its relation to reading in 117 typically developing (TD) children and 10 children
      with reading difficulties (RD) in Japan. Responses in a speech perception task
      were measured for speed, accuracy, and stability in two conditions that varied
      stimulus presentation rate: high rate and same rate conditions. TD children
      exhibited significantly more stable responses in the high rate condition than
      they did in the same rate condition. Multiple regression analyses indicated that
      response stability in the high rate condition accounted for a unique amount of
      variance in reading and mora deletion. As a group, children with RD performed
      less accurately than did TD children in the high rate condition, but not in the
      same rate condition. Findings suggest that the dependence of speech perception on
      stimulus context relates to reading proficiency or difficulty in Japanese
      children. The influences of phonology and orthography of language on the
      relationships between speech perception and reading are discussed.

PMID- 21715143
TI  - Real-time deformable registration of multi-modal whole slides for digital
      pathology.
AB  - Digital pathology provides new ways to visualize tissue slides and enables new
      workflows for analyzing these slides. Analogous to radiology, adjacent tissue
      sections prepared with different stains or biomarkers (e.g. H&E, IHC, special
      stains, or ISH; chromogenic or fluorescent) may be seen as different modalities,
      each representing different structural and/or functional information. Today, the
      anatomic pathologist views multiple glass slides using an optical microscope and
      then combines the information in their head to reach a (diagnostic) opinion.
      Moreover, due to the nature of the slide preparation and digitization process,
      the tissue and its features do not have the exact same morphology, appearance, or
      spatial alignment, making it difficult to find the same region on adjacent
      slides. To address such concerns, this paper presents a method for the spatial
      alignment of multi-modal whole slide digital microscopy images. To remain
      practical, the described method employs a two-step registration strategy designed
      to reduce computation time: the first step computes a B-spline deformable
      transform on low-resolution images prior to visualization, the second step
      applies the precomputed transformation only to the high-resolution region
      currently being viewed. The proposed method is demonstrated using a number of
      cases comprising H&E and IHC stained slides. These results indicate the
      feasibility of deformable registration for spatial alignment of multi-modal whole
      slide digital microscopy images within practical time constraints.

PMID- 21715144
TI  - Antiepileptic effects of low frequency repetitive transcranial magnetic
      stimulation: A meta-analysis.
AB  - PURPOSE: To evaluate the antiepileptic efficacy of low frequency repetitive
      transcranial magnetic stimulation (rTMS) in medically intractable epilepsy.
      METHODS: A comprehensive literature search was performed on articles published
      from 1990 to 2010 in Medline, Pubmed, CINAHL, and Cochrane using the following
      keywords: epilepsy, seizure, transcranial magnetic stimulation, repetitive
      transcranial magnetic stimulation. Two reviewers assessed article eligibility and
      extracted the data independently. For outcome measures, effect size and 95%
      confidence interval (CI) were calculated for seizure frequency, spike number,
      duration of epileptiform abnormalities (EAs), and resting motor threshold (RMT)
      by using fixed and random effect models. RESULTS: Eleven articles were
      identified, with a total of 164 participants. Based on seizure frequency, a
      significant effect size was found (effect size: 0.34, with a 95% CI at 0.10
      0.57). Considering between-study heterogeneity, we conducted a second meta
      analysis, and the underlying etiology was considered important for the treatment
      effect. Cortical dysplasia or neocortical epilepsy showed an effect size of 0.71,
      with a 95% CI at 0.30-1.12. In contrast, other epileptic disorders showed an
      effect size of 0.22. CONCLUSION: Low frequency rTMS has a favorable effect on
      seizure reduction, particularly evident in patients with neocortical epilepsy or
      cortical dysplasia.

PMID- 21715145
TI  - Dendritic cell subsets and immunological milieu in inflammatory human papilloma
      virus-related skin lesions.
AB  - BACKGROUND: Human papilloma virus (HPV)-related warts persist, evading host
      immune surveillance, but sometimes disappear with inflammation. OBJECTIVES: To
      elucidate the immune evasion mechanisms of HPV, we have examined the density,
      dynamics, and subsets of dendritic cell (DC) types in non-inflammatory or
      inflammatory HPV-related skin lesions such as warts and Bowen's disease (HPV
      Bowen), and compared the epidermal expression levels of macrophage inflammatory
      protein (MIP)-3alpha and E-cadherin. METHODS: The expression of various DC
      markers, MIP-3alpha, and E-cadherin in the tissue samples obtained from patients
      with warts, HPV-Bowen and HPV-unrelated skin diseases was evaluated by
      immunohistochemistry. MIP-3alpha gene expression levels were examined in warts
      and HPV-Bowen by in situ hybridization (ISH) and real-time quantitative
      polymerase chain reaction (RT-qPCR). RESULTS: The numbers of Langerhans cells
      (LCs) and the expression levels of MIP-3alpha and E-cadherin were decreased in
      non-inflammatory warts and HPV-Bowen, as compared with normal skin. Both
      epidermal LCs and MIP-3alpha expression reappeared in inflammatory warts,
      associated with dermal infiltrates composed of many cytotoxic T cells and various
      subsets of DCs, while cellular infiltrates in HPV-Bowen contained many B cells
      and plasma cells with sparse infiltration of DCs. The upregulation of MIP-3alpha
      gene expression was confirmed in the inflammatory warts and HPV-Bowen by ISH and
      RT-qPCR. CONCLUSIONS: The depletion of LCs in the non-inflammatory warts and HPV
      Bowen is associated with a down-regulation of expression levels of MIP-3alpha and
      E-cadherin in the lesional keratinocytes. MIP-3alpha expression is upregulated in
      lesional keratinocytes of inflammatory warts, with the subsequent recruitment of
      various DC subsets and cytotoxic T cells, whereas plasma cell-rich infiltration
      was induced in HPV-Bowen.

PMID- 21715146
TI  - Initial bacterial attachment in slow flowing systems: effects of cell and
      substrate surface properties.
AB  - Bacterial biofilm can have significant effects on the behaviors and/or
      performance of natural and man-made systems. Understanding the factors governing
      initial bacterial attachment is critical to biofilm management. In this study,
      the initial attachment of three bacteria, Pseudomonas aeruginosa, Escherichia
      coli and Pseudomonas putida, on two substrates, glass and
      octadecyltrichlorosilane (OTS) modified glass, was examined in flow chambers. The
      flow chambers were designed and operated to mimic slow moving water bodies and
      minimize the gravitational settlement of cells. The hydrophobicity of bacterial
      surface was evaluated by partitioning of cells to the water-hexadecane interface
      and the liquid contact angles on cell layers collected on filter papers. On the
      more hydrophilic glass surface, the attachment trend was found to be E. coli>P.
      putida>P. aeruginosa, while the opposite trend was observed on the hydrophobic,
      OTS modified surface. The attachment trend on glass could be explained by the
      magnitude of the negative interaction energy at secondary minima, as predicted by
      the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory. The much higher
      attachments of P. aeruginosa and P. putida on the OTS-modified substrate, on the
      other hand, suggested that these cells could overcome the energy barrier between
      the primary and secondary minima of interaction energy to become attached to the
      primary minimum. The extent of primary-minimum attachment appeared to correlate
      with the scale of the energy barrier, with higher attachments in the bacteria
      substrate combinations of lower energy barriers. The study generated important
      insights into the effects of cell and substrate surface properties on initial
      bacterial attachment.

PMID- 21715147
TI  - Development of PEG-PLA/PLGA microparticles for pulmonary drug delivery prepared
      by a novel emulsification technique assisted with amphiphilic block copolymers.
AB  - We developed a novel "spray dry-based" method for preparing surface-modified
      particle via "block copolymer-assisted" emulsification/evaporation for pulmonary
      drug delivery. The method included three steps: (1) o/w emulsion containing both
      hydrophobic polymers and amphiphilic block copolymers was obtained by
      emulsification of water and a polymer-containing organic solvent, (2) the o/w
      emulsion was misted with a nebulizer, and (3) the emulsion mists were dried by a
      heater. In this way, the hydrophobic polymers and the hydrophobic part of the
      amphiphilic block copolymers gradually tangled during the evaporation of organic
      solvents from the o/w emulsion. Consequently, the hydrophilic polymer chain was
      introduced on the particle surface. The particle surface can be easily modified
      although there are no reactive groups in the hydrophobic polymer molecules. We
      successfully obtained dry PEG-PLA/PLGA microparticles by controlling the weight
      ratio of the block copolymer and the hydrophobic polymer. The introduction of PEG
      to the particle surface involves an increase in the Zeta potential of the
      particles. Interestingly, the "dimpled" microparticles having a diameter of
      approximately 2 MUm were obtained. The "dimpled" microparticles can serve as drug
      carriers for pulmonary drug delivery, because the particles have a large surface
      area. We expect that this novel surface-modification technique will enable
      efficient fabrication of particles in drug delivery systems.

PMID- 21715148
TI  - Dissipative crystallization of aqueous mixtures of potassium salts of
      poly(riboadenylic acid) and poly(ribouridylic acid).
AB  - Dissipative drying patterns of aqueous mixtures of potassium salts of
      poly(riboadenylic acid) (KPolyA) and poly(ribouridylic acid) (KPolyU) were
      studied on a cover glass, a watch glass and a glass dish at room temperature.
      Accumulation of the polymers forming the broad rings near the outside edge and
      the inner area of the dried film was observed. The fine multiple ring structures
      formed when the affinity of the polymer with the substrate is strong. Microscopic
      drying patterns changed drastically depending on the location in the dried film.
      Microscopic drying patterns were mainly dendritic long rods and sword (halberd)
      like rods. They are assigned to the crystals of double-stranded and triple
      stranded helices of the A:U and A:2U complexes, respectively. Cross-like drying
      patterns are also observed originated from the salt-polymer interaction.

PMID- 21715149
TI  - The relation between the omega-3 index and arachidonic acid is bell shaped:
      synergistic at low EPA+DHA status and antagonistic at high EPA+DHA status.
AB  - INTRODUCTION: The relation between docosahexaenoic (DHA) and eicosapentaenoic
      (EPA) vs. arachidonic acid (AA) seems characterized by both synergism and
      antagonism. MATERIALS AND METHODS: Investigate the relation between EPA+DHA and
      AA in populations with a wide range of EPA+DHA status and across the life cycle.
      EPA+DHA and AA were determined in erythrocytes (RBC; n=1979), umbilical arteries
      (UA; n=789) and umbilical veins (UV; n=785). RESULTS: In all compartments,
      notably RBC, the relation between EPA+DHA and AA appeared bell-shaped.
      Populations with low RBC-EPA+DHA (<2g%) exhibited positive relationships; those
      with high RBC-EPA+DHA (>8g%) negative relationships. Antagonism in UA and UV
      could not be demonstrated. CONCLUSION: Both synergism and antagonism might aim at
      a balance between omega6 and omega3 long-chain polyunsaturated fatty acid (LCP)
      to maintain homeostasis. Synergism might be a feature of low LCPomega3 status. AA
      becomes suppressed by antagonism from an RBC-EPA+DHA >8g%.

PMID- 21715150
TI  - An unusual preinduction arrhythmia resulting from the presence of a Mahaim fiber.
AB  - A potentially life-threatening arrhythmia appeared on the preinduction
      electrocardiogram of an asymptomatic young woman prior to spine surgery. The
      patient was evaluated by electrophysiology and had a rare accessory pathway, a
      Mahaim Fiber.

PMID- 21715151
TI  - The two faces of alpha- and gamma-tocopherols: an in vitro and ex vivo
      investigation into VLDL, LDL and HDL oxidation.
AB  - BACKGROUND: Vitamin E and its derivatives, namely, the tocopherols, are known
      antioxidants, and numerous clinical trials have investigated their role in
      preventing cardiovascular disease; however, evidence to date remains
      inconclusive. Much of the in vitro research has focused on tocopherol's effects
      during low-density lipoprotein (LDL) oxidation, with little attention being paid
      to very LDL (VLDL) and high-density lipoprotein (HDL). Also, it is now becoming
      apparent that gamma-tocopherol may potentially be more beneficial in relation to
      cardiovascular health. OBJECTIVES: Do alpha- and gamma-tocopherols become
      incorporated into VLDL, LDL and HDL and influence their oxidation potential in an
      in vitro and ex vivo situation? DESIGN: Following (i) an in vitro investigation,
      where plasma was preincubated with increasing concentrations of either alpha- or
      gamma-tocopherol and (ii) an in vivo 4-week placebo-controlled intervention with
      alpha- or gamma-tocopherol. Tocopherol incorporation into VLDL, LDL and HDL was
      measured via high-pressure liquid chromatography, followed by an assessment of
      their oxidation potential by monitoring conjugated diene formation. RESULTS: In
      vitro: Both tocopherols became incorporated into VLDL, LDL and HDL, which
      protected VLDL and LDL against oxidation. However and surprisingly, the
      incorporation into HDL demonstrated pro-oxidant properties. Ex vivo: Both
      tocopherols were incorporated into all three lipoproteins, protecting VLDL and
      LDL against oxidation; however, they enhanced the oxidation of HDL. CONCLUSIONS:
      These results suggest that alpha- and gamma-tocopherols display conflicting
      oxidant activities dependent on the lipoprotein being oxidized. Their pro-oxidant
      activity toward HDL may go some way to explain why supplementation studies with
      vitamin E have not been able to display cardioprotective effects.

PMID- 21715152
TI  - SimAmph: an agent-based simulation model for exploring the use of
      psychostimulants and related harm amongst young Australians.
AB  - BACKGROUND: Computer simulations provide a useful tool for bringing together
      diverse sources of information in order to increase understanding of the complex
      aetiology of drug use and related harm, and to inform the development of
      effective policies. In this paper, we describe SimAmph, an agent-based simulation
      model for exploring how individual perceptions, peer influences and subcultural
      settings shape the use of psychostimulants and related harm amongst young
      Australians. METHODS: We present the conceptual architecture underpinning
      SimAmph, the assumptions we made in building it, the outcomes of sensitivity
      analysis of key model parameters and the results obtained when we modelled a
      baseline scenario. RESULTS: SimAmph's core behavioural algorithm is able to
      produce social patterns of partying and recreational drug use that approximate
      those found in an Australian national population survey. We also discuss the
      limitations involved in running closed-system simulations and how the model could
      be refined to include the social, as well as health, consequences of drug use.
      CONCLUSION: SimAmph provides a useful tool for integrating diverse data and
      exploring drug policy scenarios. Its integrated approach goes some way towards
      overcoming the compartmentalisation that characterises existing data, and its
      structure, parameters and values can be modified as new data and understandings
      emerge. In a companion paper (Dray et al., 2011), we use the model outlined here
      to explore the possible consequences of two policy scenarios.

PMID- 21715153
TI  - A cyclodextrin host-guest recognition approach to an electrochemical sensor for
      simultaneous quantification of serotonin and dopamine.
AB  - An electrochemical sensor for simultaneous quantification of serotonin (5
      hydroxytryptamine, 5-HT) and dopamine (DA) using a beta-cyclodextrin/poly(N
      acetylaniline)/carbon nanotube composite modified carbon paste electrode has been
      developed. Synergistic effect of multi-walled carbon nanotube (MWCNT) in addition
      to the pre-concentrating effect of beta-cyclodextrin (beta-CD) as well as its
      different inclusion complex stability with 5-HT and DA was used to construct an
      electrochemical sensor for quantification of these important neurotransmitters.
      The overlapping anodic peaks of 5-HT and DA at 428 mV on bare electrode resolved
      in two well-defined voltammetric peaks at 202 and 363 mV vs. Ag/AgCl
      respectively. The oxidation mechanism of 5-HT and DA on the surface of the
      electrode was investigated by cyclic voltammetry and it was found that the
      electrode processes are pH dependent and electrochemical oxidation of 5-HT is
      totally irreversible while the electrode gave a more reversible process to DA.
      Under optimized conditions, linear calibration curves were obtained in the range
      of about 4-200 MUM with a detection limits down to sub-MUM levels (S/N=3) after
      20-s accumulation, for both. The proposed sensor was shown to be remarkably
      selective for 5-HT and DA in matrices containing different species including
      ascorbic acid and uric acid. The suitability of the developed method was tested
      for the determination of 5-HT and DA in the Randox Synthetic Plasma samples and
      acceptable recoveries were obtained for a set of spiked samples.

PMID- 21715154
TI  - A microfluidic biochip for the nanoporation of living cells.
AB  - This paper deals with the development of a microfluidic biochip for the exposure
      of living cells to nanosecond pulsed electric fields (nsPEF). When exposed to
      ultra short electric pulses (typical duration of 3-10ns), disturbances on the
      plasma membrane and on the intra cellular components occur, modifying the
      behavioral response of cells exposed to drugs or transgene vectors. This
      phenomenon permits to envision promising therapies. The presented biochip is
      composed of thick gold electrodes that are designed to deliver a maximum of
      energy to the biological medium containing cells. The temporal and spectral
      distributions of the nsPEF are considered for the design of the chip. In order to
      validate the fabricated biochip ability to orient the pulse towards the cells
      flowing within the exposition channels, a frequency analysis is provided. High
      voltage measurements in the time domain are performed to characterize the
      amplitude and the shape of the nsPEF within the exposition channels and compared
      to numerical simulations achieved with a 3D Finite-Difference Time-Domain code.
      We demonstrate that the biochip is adapted for 3 ns and 10 ns pulses and that the
      nsPEF are homogenously applied to the biological cells regardless their position
      along the microfluidic channel. Furthermore, biological tests performed on the
      developed microfluidic biochip permit to prove its capability to permeabilize
      living cells with nanopulses. To the best of our knowledge, we report here the
      first successful use of a microfluidic device optimized for the achievement and
      real time observation of the nanoporation of living cells.

PMID- 21715155
TI  - DARPins and other repeat protein scaffolds: advances in engineering and
      applications.
AB  - Antibodies have long been regarded as the only class of binding proteins. With
      the emergence of protein engineering techniques, new binding proteins based on
      alternative scaffolds have been designed. Additionally, modern technologies for
      selection and evolution from libraries are independent of the antibody scaffold
      and could thus be readily used for obtaining specific binding proteins. One
      important group of alternative scaffolds is based on repeat proteins. Nature is
      widely using these proteins to modulate protein-protein interactions, and even in
      the adaptive immune system of jawless vertebrates; the step to their application
      as an alternative to antibodies seems therefore logical. In this review, progress
      on DARPins and other repeat protein scaffolds will be discussed. Advances in
      their design as well as novel applications will be highlighted.

PMID- 21715156
TI  - Intracellular and computational evidence for a dominant role of internal network
      activity in cortical computations.
AB  - The mammalian cerebral cortex is characterized by intense spontaneous activity,
      depending on brain region, age, and behavioral state. Classically, the cortex is
      considered as being driven by the senses, a paradigm which corresponds well to
      experiments in quiescent or deeply anesthetized states. In awake animals,
      however, the spontaneous activity cannot be considered as 'background noise', but
      is of comparable-or even higher-amplitude than evoked sensory responses. Recent
      evidence suggests that this internal activity is not only dominant, but also it
      shares many properties with the responses to natural sensory inputs, suggesting
      that the spontaneous activity is not independent of the sensory input. Such
      evidence is reviewed here, with an emphasis on intracellular and computational
      aspects. Statistical measures, such as the spike-triggered average of synaptic
      conductances, show that the impact of internal network state on spiking activity
      is major in awake animals. Thus, cortical activity cannot be considered as being
      driven by the senses, but sensory inputs rather seem to modulate and modify the
      internal dynamics of cerebral cortex. This view offers an attractive
      interpretation not only of dreaming activity (absence of sensory input), but also
      of several mental disorders.

PMID- 21715157
TI  - On-field study of anaerobic digestion full-scale plants (part I): an on-field
      methodology to determine mass, carbon and nutrients balance.
AB  - The mass balance (input/output mass flows) of full-scale anaerobic digestion (AD)
      processes should be known for a series of purposes, e.g. to understand carbon and
      nutrients balances, to evaluate the contribution of AD processes to elemental
      cycles, especially when digestates are applied to agricultural land and to
      measure the biodegradation yields and the process efficiency. In this paper,
      three alternative methods were studied, to determine the mass balance in full
      scale processes, discussing their reliability and applicability. Through a 1-year
      survey on three full-scale AD plants and through 38 laboratory-scale batch
      digesters, the congruency of the considered methods was demonstrated and a linear
      equation was provided that allows calculating the wet weight losses (WL) from the
      methane produced (MP) by the plant (WL=41.949*MP+20.853, R(2)=0.950, p<0.01).
      Additionally, this new tool was used to calculate carbon, nitrogen, phosphorous
      and potassium balances of the three observed AD plants.

PMID- 21715158
TI  - Temperature dependent (37-15 degrees C) anaerobic digestion of a
      trichloroethylene-contaminated wastewater.
AB  - The impact of a trichloroethylene (TCE) contaminated wastewater on the microbial
      community structure of an anaerobic granular biomass at 15 degrees C compared to
      37 degrees C was investigated. Four expanded granular sludge bed (EGSB)
      bioreactors (R1-R4) were employed in pairs at 37 and 15 degrees C. The influents
      of one of each pair were supplemented with increasing concentrations of TCE (max.
      60 mgl(-1)). At 37 degrees C, stable operation was maintained with 88% COD
      removal and >99% TCE removal at maximum influent TCE concentrations. R3
      performance decreased at influent TCE concentration of 60 mgl(-1), although TCE
      removal rates of >97% were recorded. Archaeal community analysis via clone
      library and quantitative polymerase chain reaction (qPCR) analysis, and bacterial
      community analysis via denaturing gradient gel electrophoresis (DGGE), indicated
      that temperature resulted in a greater change in community structure than the
      presence of TCE, and clones related to cold adaptation of biomass were identified
      at 15 degrees C.

PMID- 21715159
TI  - Degumming of vegetable oils by a novel phospholipase B from Pseudomonas
      fluorescens BIT-18.
AB  - Pseudomonas fluorescens BIT-18 was isolated from soil near a vegetable oil
      factory and shown to produce a B-type phospholipase. The enzyme was partially
      purified by ammonium sulfate precipitation. Gas chromatography demonstrated that
      the enzyme preparation hydrolyzed both the 1- and 2-ester bonds of
      phosphatidylcholine. When degumming of soybean, rapeseed, and peanut oil was
      performed with this enzyme preparation, oils with phosphorous contents lower than
      5mg/kg were obtained after 5h of enzyme treatment at 40 degrees C. The enzyme
      preparation did not show lipase activity, thus free fatty acids were only
      generated from the phospholipids. Therefore, this novel phospholipase B is
      potentially useful for the refining of high-quality oils with attractive yields.

PMID- 21715160
TI  - A critical comparison of methyl and ethyl esters production from soybean and rice
      bran oil in the presence of microwaves.
AB  - Transesterification of vegetable oils (from soybeans and rice bran) into methyl
      and ethyl esters using a batch microwave system was investigated in this study. A
      critical comparison between the two alcohols was performed in terms of yields,
      quality, and reaction kinetics. Parameters tested were temperature (60, 70 and 80
      degrees C) and time (5, 10, 15 and 20 min). At all tested conditions, more than
      96% conversion rates were obtained for both ethanol and methanol. Use of
      microwave technology to assist the transesterification process resulted in faster
      reaction times and reduced catalyst requirement (about ten-fold decrease).
      Methanol required lower alcohol:oil ratios than normally used in conventional
      heating, whereas ethanol required higher molar ratios. All esters produced using
      this method met ASTM biodiesel quality specifications. Methanol performed better
      in terms of performance and costs, while ethanol may have some environmental and
      safety benefits.

PMID- 21715161
TI  - Performance and macrokinetic analysis of biofiltration of toluene and p-xylene
      mixtures in a conventional biofilter packed with inert material.
AB  - Interactions of toluene and p-xylene in air treatment biofilters packed with an
      inert filter media were studied. The effect of the inlet load of toluene, p
      xylene and mixtures of both compounds on the biodegradation rate was analyzed in
      three lab-scale biofilters. A maximum elimination capacity (EC) of 26.5 and 40.3
      gCm(-3)h(-1) for an inlet load (IL) of 65.6 and 57.8 gCm(-3)h(-1) was obtained
      for p-xylene and toluene biofilters, respectively. Inhibition of p-xylene
      biodegradation by the presence of toluene took place when the mixture was
      treated, whereas the presence of p-xylene had an enhancing effect on the toluene
      removal efficiency. Specific growth rates (MU) from 0.019 to 0.068 h(-1) were
      calculated in the mixed biofilter, where the highest values were similar to
      mixtures with lower p-xylene levels (IL(p-Xyl) 8.84 +/- 0.29 gCm(-3)h(-1)).
      Michaelis-Menten and Haldane type models were fitted to experimental EC for p
      xylene and toluene biofilters, respectively.

PMID- 21715162
TI  - Degradation of petroleum hydrocarbons (C6-C40) and crude oil by a novel Dietzia
      strain.
AB  - A novel bacterial strain, DQ12-45-1b, was isolated from the production water of a
      deep subterranean oil-reservoir. Morphological, physiological and phylogenetic
      analyses indicated that the strain belonged to the genus Dietzia with both alkB
      (coding for alkane monooxygenase) and CYP153 (coding for P450 alkane hydroxylase
      of the cytochrome CYP153 family) genes and their induction detected. It was
      capable of utilizing a wide range of n-alkanes (C6-C40), aromatic compounds and
      crude oil as the sole carbon sources for growth. In addition, it preferentially
      degraded short-chain hydrocarbons (<=C25) in the early cultivation phase and
      accumulated hydrocarbons with chain-lengths from C23 to C27 during later
      cultivation stage with crude oil as the sole carbon source. This is the first
      study to report the different behaviors of a bacterial species toward crude oil
      degradation as well as a species of Dietzia degrading a wide range of
      hydrocarbons.

PMID- 21715163
TI  - Changes in lipid, fatty acids and phospholipids composition of whole rice bran
      after solid-state fungal fermentation.
AB  - The aim of this study was to evaluate fermented rice bran phospholipids, lipids
      and fatty acid content in a fermentation solid system with Rhizopus oryzae
      fungus. For this, aliquots were withdrawn every 24h over 120 h. The content of
      phospholipids was determined by colorimetric method. Esterified fatty acids were
      separated by gas chromatography, then identified and quantified. The total lipids
      from fermented rice bran (FB) decreased from 20.4% to 11.2% in the range between
      0 h and 120 h of fermentation while phospholipid contents were increased up to
      2.4 mg P g(lipid)(-1). In fermented bran, oleic, palmitic and linoleic acids
      prevailed, with a decrease in saturated fatty acids (20%) and increase in the
      unsaturated ones (5%). This study showed that rice bran fermentation with R.
      oryzae can be applied to the production of phospholipids altering the saturated
      to unsaturated fatty acid ratio.

PMID- 21715164
TI  - Coupling of anodic biooxidation and cathodic bioelectro-Fenton for enhanced swine
      wastewater treatment.
AB  - A novel bioelectrochemical reactor with anodic biooxidation coupled to cathodic
      bioelectro-Fenton was developed for the enhanced treatment of highly concentrated
      organic wastewater. Using swine wastewater as a model, the anode-cathode coupled
      system was demonstrated to be both efficient and energy-saving. Without any
      external energy supply to the system, BOD(5), COD, NH(3)-N and TOC in the
      wastewater could be greatly reduced at both 1.1g COD L(-1)d(-1) and 4.6g COD L(
      1)d(-1) of OLR, with the overall removal rates ranging from 62.2% to 95.7%.
      Simultaneously, electricity was generated at around 3-8 Wm(-3) of maximum output
      power density. Based on electron balance calculation, 60-65% of all the electrons
      produced from anodic biooxidation were consumed in the cathodic bioelectro-Fenton
      process. This coupled system has a potential for enhanced treatment of high
      strength wastewater and provides a new way for efficient utilization of the
      electron generated from biooxidation of organic matters.

PMID- 21715165
TI  - Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which
      significantly decreases tumor volume in a mouse xenograft model.
AB  - An extension of our previously reported series of macrocyclic ortho
      aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to
      the tether provided analogs that show increased potency in binding as well as
      cell-proliferation assays and, more importantly, are stable toward microsomes. We
      wish to disclose the discovery of a macrocycle which showed impressive biomarker
      activity 24-h post dosing and which demonstrated prolonged exposure in tumors.
      When studied in a lung cancer xenograft model, the compound demonstrated
      significant tumor size reduction.

PMID- 21715166
TI  - Repetitive stepping in place identifies and measures freezing episodes in
      subjects with Parkinson's disease.
AB  - Freezing of gait (FOG) in Parkinson's disease (PD) is challenging to measure. We
      asked whether a repetitive stepping in place (SIP) task on force plates could
      identify freezing episodes (FEs) in PD subjects, self-classified as "freezers",
      using the validated FOG questionnaire (FOG-Q) and whether a computerized
      algorithm could provide automatic detection of FEs during SIP. Thirty PD subjects
      and nine age-matched controls completed the SIP task. PD subjects were assessed
      using the Unified Parkinson's Disease Rating motor Scale (UPDRS-III) and the FOG
      Q. The identification of "freezers" using the SIP task correlated with the FOG-Q
      (r=0.80, P<0.001). The specificity and sensitivity of identifying freezers using
      the SIP task reached 93% and 87%. The number and duration of FEs detected by the
      algorithm correlated with visual inspection (r=0.97, r=0.998, P<0.001). Freezers
      had larger SIP asymmetry compared to controls (P=0.02) and non-freezers (P=0.03)
      as well as larger arhythmicity (P=0.003 and P<0.001, respectively). UPDRS
      subscores were higher in freezers compared to non-freezers (P<0.05). These
      results suggest that the SIP task is a useful tool to detect freezing in PD and
      is correlated with FOG-Q. SIP cycle asymmetry and stride time variability were
      worse in freezers, similar to that shown in FOG studies. Detection of the number
      and duration of FEs using a computerized algorithm correlated with independent
      visual inspection of records.

PMID- 21715167
TI  - Quantification of inertial sensor-based 3D joint angle measurement accuracy using
      an instrumented gimbal.
AB  - This study quantified the accuracy of inertial sensors in 3D anatomical joint
      angle measurement with respect to an instrumented gimbal. The gimbal rotated
      about three axes and directly measured the angles in the ISB recommended knee
      joint coordinate system. Through the use of sensor attachment devices physically
      fixed to the gimbal, the joint angle estimation error due to sensor attachment
      (the inaccuracy of the sensor attachment matrix) was essentially eliminated,
      leaving only error due to the inertial sensors. The angle estimation error (RMSE)
      corresponding to the sensor was found to be 3.20 degrees  in flexion/extension,
      3.42 degrees  in abduction/adduction and 2.88 degrees  in internal/external
      rotation. Bland-Altman means of maximum absolute value were -1.63 degrees 
      inflexion/extension, 3.22 degrees  in abduction/adduction and -2.61 degrees  in
      internal/external rotation. The magnitude of the errors reported in this study
      imply that even under ideal conditions irreproducible in human gait studies,
      inertial angle measurement will be subject to errors of a few degrees.
      Conversely, the reported errors are smaller than those reported previously in
      human gait studies, which suggest that the sensor attachment is also significant
      source of error in inertial gait measurement. The proposed apparatus and
      methodology could be used to quantify the performance of different sensor systems
      and orientation estimation algorithms, and to verify experimental protocols
      before human experimentation.

PMID- 21715168
TI  - Aging effects on object transport during gait.
AB  - The ability to manipulate objects deteriorates with increasing age. In the
      coordination of fingertip forces underlying object manipulation, older adults use
      excessive grip (normal) forces but maintain anticipatory force control during
      simple manipulations. Daily activities are often more complex and involve grasp
      manipulations while simultaneously performing other activities. When walking
      while carrying an object, young adults couple grip forces to gait-induced
      inertial force changes (anticipatory control). It is unclear if anticipatory
      control is preserved in older adults during demanding tasks. The purpose of this
      study was therefore to investigate aging effects on grasp control when walking
      and transporting an object. We included gait perturbations to vary task
      difficulty and step regularity associated with walking. Twelve healthy older (65
      84 years) and young (20-30 years) adults transported a hand-held object during
      unperturbed walking, obstacle crossing and step-length changes. While older
      subjects employed higher grip-inertial force ratios, they showed a strong force
      coupling comparable to that of the young during unperturbed walking and step
      length changes. During obstacle crossing the forces in the older group were less
      tightly coupled (grip force delays). Gait patterns were similar between groups.
      Our findings indicate that older adults maintain anticipatory control during
      regular and irregular walking. Grasp control changes in older adults only during
      obstacle crossing suggest that overall task demands (balance requirements,
      attention demands) may contribute to declines of manual dexterity in functional
      tasks. This highlights the need to investigate grasp control within complex tasks
      when aiming to understand impairments of older adults encountered in daily life.

PMID- 21715169
TI  - Hip joint centre localization: Evaluation on normal subjects in the context of
      gait analysis.
AB  - Locating the position of the hip joint centre (HJC) is an important part of lower
      limb modeling for gait analysis. Regression equations have been used in the past
      but a range of functional calibration methods are now available. This study
      compared the accuracy of HJC localization from two sets of regression equations
      and five different functional calibration methods against three dimensional
      ultrasound (3-DUS) on a population of 19 able bodied subjects. Results show that
      the geometric sphere fitting technique was the best performer with mean absolute
      distance error of 15mm and 85% of measurements being within 20mm. The results
      also show that widely used regression equations perform particularly badly
      whereas the most recent equations performed very closely to the best functional
      method with a mean absolute error of 16mm and 88% of measurements being within
      20mm. In vivo results are more than an order of magnitude worse than predictions
      using synthetic data suggesting that additional work is required before soft
      tissue artifact can be effectively modelled.

PMID- 21715170
TI  - Calculations of mechanisms for balance control during narrow and single-leg
      standing in fit older adults: A reliability study.
AB  - For older people balance control in standing is critical for performance of
      activities of daily living without falling. The aims were to investigate
      reliability of quantification of the usage of the two balance mechanisms M(1)
      'moving the centre of pressure' and M(2) 'segment acceleration' and also to
      compare calculation methods based on a combination of kinetic (K) and kinematic
      (Km) data, (K-Km), or Km data only concerning M(2). For this purpose nine
      physically fit persons aged 70-78 years were tested in narrow and single-leg
      standing. Data were collected by a 7-camera motion capture system and two force
      plates. Repeated measure ANOVA and Tukey's post hoc tests were used to detect
      differences between the standing tasks. Reliability was estimated by ICCs,
      standard error of measurement including its 95% CI, and minimal detectable
      change, whereas Pearson's correlation coefficient was used to investigate
      agreement between the two calculation methods. The results indicated that for the
      tasks investigated, M(1) and M(2) can be measured with acceptable inter- and
      intrasession reliability, and that both Km and K-Km based calculations may be
      useful for M(2), although Km data may give slightly lower values. The
      proportional M(1):M(2) usage was approximately 9:1, in both anterio-posterior
      (AP) and medio-lateral (ML) directions for narrow standing, and about 2:1 in the
      AP and of 1:2 in the ML direction in single-leg standing, respectively. In
      conclusion, the tested measurements and calculations appear to constitute a
      reliable way of quantifying one important aspect of balance capacity in fit older
      people.

PMID- 21715171
TI  - A phase I/II clinical trial investigating the adverse and therapeutic effects of
      a postoperative autologous dendritic cell tumor vaccine in patients with
      malignant glioma.
AB  - Previous clinical trials of dendritic cell (DC)-based immunotherapy in patients
      with glioblastoma multiforme (GBM) have reported induction of systemic immune
      responses and prolonged survival. From 2003 to 2005, we performed a clinical
      trial in which patients with malignant glioma underwent surgery for maximal
      cytoreduction followed by a 6-month 10-injection course of autologous DC-tumor
      vaccine therapy, each injection containing 1-6*10(7) DC. Of the 17 treated
      patients (16 with World Health Organization grade IV and one with grade III
      glioma), eight (47.1%) had an initial transient elevation in aspartate
      aminotransferase (AST)/alanine aminotransferase (ALT). Vaccination caused some
      tumor shrinkage and increased concentration of tumor-infiltrating CD8(+)
      lymphocytes. Median survival and 5-year survival were 525 days and 18.8%,
      respectively, for 16 patients with grade IV glioma (381 days and 12.5% for eight
      newly diagnosed; 966 days and 25% for eight relapsed patients) compared to 380
      days and 0% for 63 historical control patients. We concluded that autologous DC
      tumor immunotherapy benefits patients with malignant glioma but may cause
      transient but reversible elevation of serum AST/ALT levels.

PMID- 21715172
TI  - An historical view of the pineal gland and mental disorders.
AB  - Since Classical Antiquity numerous authors have linked the origin of some mental
      disorders to physical and functional changes in the pineal gland because of its
      attributed role in humans as the connection between the material and the
      spiritual world. The pineal organ was seen as a valve-like structure that
      regulated the flow of animal spirits through the ventricular system, a hypothesis
      that took on more vigour during the Middle Ages and the Renaissance. The
      framework for this theory was "the three cells of the brain", in which the pineal
      gland was even called the "appendix of thought". The pineal gland could also be
      associated with the boom, during this period, of certain legends about the "stone
      of folly". But the most relevant psychopathological role of this organ arrived
      with Descartes, who proposed that it was the seat of the human soul and
      controlled communications between the physical body and its surroundings,
      including emotions. After a period of decline during which it was considered as a
      mere vestigial remnant of evolution, the link between the pineal gland and
      psychiatric disorders was definitively highlighted in the 20th century, first
      with the use of glandular extracts in patients with mental deficiency, and
      finally with the discovery of melatonin in 1958. The physiological properties of
      melatonin reawakened interest in the relationship between the pineal gland and
      mental disorders, fundamentally the affective and sleep disorders, which
      culminated in the development of new pharmacological agents acting through
      melatonergic receptors (ramelteon and agomelatine).

PMID- 21715173
TI  - Intraoperative near-infrared indocyanine green-videoangiography (ICG-VA) and
      graphic analysis of fluorescence intensity in cerebral aneurysm surgery.
AB  - We present our preliminary experience with intraoperative near-infrared
      indocyanine green-videoangiography (ICG-VA) and analysis of blood flow dynamics
      using fluorescence intensity assessment in cerebral aneurysm clipping surgery.
      Thirty-nine patients with 43 intracranial aneurysms underwent microsurgical
      clipping. Intraoperative ICG-VA was performed before and after clip application.
      An infrared fluorescence module integrated into a surgical microscope was used to
      visualize fluorescence in the surgical field and we recorded the emitted
      fluorescent light. An integrated analytical visualization tool simultaneously
      analyzed the video sequence and converted it into an intensity diagram, which
      allowed an objective evaluation of the results rather than the subjective
      assessment of fluorescence using ICG-VA. Overall, ICG-VA was performed 137 times.
      Incomplete clipping was detected in four patients, which allowed suitable
      adjustment to completely obliterate the aneurysm. In 12 patients, perforators
      arising close to, or from, the aneurysmal neck were identified in the surgical
      field. In three patients, the ICG-VA intensity diagram provided valuable
      information leading to modification of the primary surgical maneuver. ICG-VA
      provides high resolution images allowing real-time assessment of the blood flow
      in the parent artery and arterial branches, including the perforators. The
      intensity diagram is useful for providing a more objective record of the
      hemodynamics than the traditional ICG-VA, which relies more on subjective
      assessment and may allow interobserver variability. We conclude that ICG-VA,
      combined with the intensity diagram, can reduce the morbidity and complications
      associated with aneurysm clipping and improve patient outcomes.

PMID- 21715174
TI  - Patients with Type 2 diabetes mellitus have a worse functional outcome post knee
      arthroplasty: a matched cohort study.
AB  - Knee arthroplasty provides not only pain relief but also an improvement in
      function and range of movement. Limited joint mobility is a common complication
      of diabetes mellitus. We therefore examined functional outcome post total knee
      arthroplasty in a cohort of subjects with (n=367) and a cohort matched for age,
      sex, BMI and functional movement at baseline, without diabetes mellitus (n=367).
      Participants were examined at baseline (pre-operatively), 1, 5 and 10 years post
      TKA. There was no significant difference in fixed flexion, maximal flexion or
      total range of movement between the two groups at baseline. By 1 year the group
      with diabetes had a significantly lower maximal flexion (p<0.001), total range of
      movement (p<0.001) and Knee Society Score (p=0.034). Similar results were
      observed at years 5 (except for the KSS) and 10 post procedure. At 5 years post
      arthroplasty a significant increase was observed in fixed flexion (p=0.026) in
      the diabetic group. Ten years post arthroplasty yielded similar results. This
      study demonstrates that the pre-operative presence of diabetes mellitus leads to
      a worse outcome post knee arthroplasty, although no significant difference was
      demonstrable in KSS at 5 years (p=0.35) suggesting patient satisfaction remains
      high during this period.

PMID- 21715175
TI  - The intra- and inter-observer reliability of the physical examination methods
      used to assess patients with patellofemoral joint instability.
AB  - BACKGROUND: An accurate physical examination of patients with patellar
      instability is an important aspect of the diagnosis and treatment. While previous
      studies have assessed the diagnostic accuracy of such physical examination tests,
      little has been undertaken to assess the inter- and intra-tester reliability of
      such techniques. The purpose of this study was to determine the inter- and intra
      tester reliability of the physical examination tests used for patients with
      patellar instability. METHODS: Five patients (10 knees) with bilateral recurrent
      patellar instability were assessed by five members of the International
      Patellofemoral Study Group. Each surgeon assessed each patient twice using 18
      reported physical examination tests. The inter- and intra-observer reliability
      was assessed using weighted Kappa statistics with 95% confidence intervals.
      RESULTS: The findings of the study suggested that there were very poor inter
      observer reliability for the majority of the physical tests, with only the
      assessments of patellofemoral crepitus, foot arch position and the J-sign
      presenting with fair to moderate agreement respectively. The intra-observer
      reliability indicated largely moderate to substantial agreement between the first
      and second tests performed by each assessor, with the greatest agreement seen for
      the assessment of tibial torsion, popliteal angle and the Bassett's sign.
      CONCLUSIONS: For the common physical examination tests used in the management of
      patients with patellar instability inter-observer reliability is poor, while
      intra-observer reliability is moderate. Standardization of physical exam
      assessments and further study of these results among different clinicians and
      more divergent patient groups is indicated.

PMID- 21715176
TI  - G-quadruplex DNA aptamers generated for systemin.
AB  - Ligands specific to bioactive molecules play important roles in biomedical
      researches and applications, such as biological assay, diagnosis and therapy.
      Systemin is a peptide hormone firstly identified in plant. In this paper we
      report the selection of a group of DNA aptamers that can specifically bind to
      systemin. Through comparing the predicted secondary structures of all the
      aptamers, a hairpin structure with G-rich loop was determined to be the binding
      motif of these aptamers. The G-rich loop region of this binding motif was further
      characterized to fold into an antiparallel G-quadruplex by truncation-mutation
      assay and CD spectrum. The apparent equilibrium dissociation constant (K(d)) of
      one strong binding sequence (S-5-1) was measured to be 0.5 MUM. The specificity
      assay shows that S-5-1 strongly bind to whole systemin, weakly bind to truncated
      or mutated systemin and does not bind to the scrambled peptide with the same
      amino acid composition as systemin. The high affinity and specificity make S-5-1
      hold potentials to serve as a molecular ligand applied in detection, separation
      and functional investigation of systemin in plants.

PMID- 21715177
TI  - Ptilomycalin A inhibits laccase and melanization in Cryptococcus neoformans.
AB  - The antifungal spirocyclic guanidine alkaloid, ptilomycalin A, from marine sponge
      Monanchora arbuscula, inhibits melanogenesis of Cryptococcus neoformans in vitro
      through inhibition of biosynthesis of laccase in the melanin biosynthetic pathway
      with an IC(50) of 7.3 MUM.

PMID- 21715179
TI  - Three dimensional microvascular measurements in human endometrium using optical
      slices from laser scanning confocal microscopy (LSCM).
AB  - There is increasing interest in the structure of the microvascular environment in
      human endometrium because of the recognition of the complexity and functional
      importance of this tissue. Endometrial microcirculatory networks and their
      relationships have rarely been studied in three-dimensions. Longitudinal uterine
      slices containing endometrial tissue were carefully selected from women
      undergoing a hysterectomy. Formalin-fixed endometrial sections (<= 50 MUm)
      representing the fundal and isthmic regions were immunofluorescently labeled with
      monoclonal antibody (CD34) to target the endothelium of microvessel and
      fluorescein isothiocyanate (FITC) labeled goat anti-mouse. Digital images were
      acquired using a Nikon Eclipse E800 microscope equipped with a Radiance 2000
      confocal scanning laser attachment. ImarisBasic 4.1 visualization suite was
      utilized for qualitative interpretation. NeuronTracer 1.0 software was utilized
      to derive the length and numerical densities. There were significant changes
      across the phases of the menstrual cycle in functional and basal endometrial
      layers in vessel length density (LD(v)) and branch point density (ND(v)) within
      both fundal and isthmic regions of the uterus (P<0.001). There was also a
      significant effect of menstrual cycle phase on mean vessel segment length (SL(v))
      within each region and within each of the layers (P<0.001). The capillary radial
      diffusion distance r(diff) was negatively correlated with LD(v). In general,
      within each of the menstrual cycle phases, LD(v), ND(v) were greater in the
      fundal than the isthmic regions while, in contrast, SL(v) was found to be
      greatest in the isthmic region. Utilization of immunofluorescence and laser
      scanning confocal microscopy has enabled us to demonstrate significant vascular
      changes in human endometrial layers illustrating that in general, within each of
      the menstrual cycle phases, vessel length and branch point densities were greater
      in the fundal than the isthmic regions, while vessel segment lengths were found
      to be greatest in the isthmic region.

PMID- 21715178
TI  - Survey of marine natural product structure revisions: a synergy of spectroscopy
      and chemical synthesis.
AB  - The structural assignment of new natural product molecules supports research in a
      multitude of disciplines that may lead to new therapeutic agents and or new
      understanding of disease biology. However, reports of numerous structural
      revisions, even of recently elucidated natural products, inspired the present
      survey of techniques used in structural misassignments and subsequent revisions
      in the context of constitutional or configurational errors. Given the
      comparatively recent development of marine natural products chemistry, coincident
      with modern spectroscopy, it is of interest to consider the relative roles of
      spectroscopy and chemical synthesis in the structure elucidation and revision of
      those marine natural products that were initially misassigned. Thus, a tabulated
      review of all marine natural product structural revisions from 2005 to 2010 is
      organized according to structural motif revised. Misassignments of constitution
      are more frequent than perhaps anticipated by reliance on HMBC and other advanced
      NMR experiments, especially when considering the full complement of all natural
      products. However, these techniques also feature prominently in structural
      revisions, specifically of marine natural products. Nevertheless, as is the case
      for revision of relative and absolute configuration, total synthesis is a proven
      partner for marine, as well as terrestrial, natural products structure
      elucidation. It also becomes apparent that considerable 'detective work' remains
      in structure elucidation, in spite of the spectacular advances in spectroscopic
      techniques.

PMID- 21715180
TI  - Is tranexamic acid really an alternative to aprotinin?

PMID- 21715181
TI  - Passive peritoneal drainage improves fluid balance after surgery for congenital
      heart disease.
AB  - OBJECTIVE: In some centers, passive peritoneal drainage (PD) is implemented
      following surgery for congenital heart disease. The utility of this practice has
      yet to be studied. We hypothesized that passive PD can promote negative fluid
      balance without compromising intravascular volume. METHODS: A retrospective
      review of infants who underwent repair of complete atrioventricular septal defect
      (AVSD) between 6/2006 and 8/2010 was completed. Data are represented as mean +/-
      standard deviation. RESULTS: Thirty-six infants underwent AVSD repair, 18 of whom
      had PD catheters placed without complication. Infants with passive PD had longer
      duration of cardiopulmonary bypass (211 +/- 59 vs 137 +/- 41 min, P < 0.001) and
      aortic cross-clamp (148 +/- 29 vs 102 +/- 21 min, P < 0.001); had higher
      Aristotle complexity score (12.6 +/- 3 vs 10.7 +/- 2, P = 0.03) and ventilatory
      support immediately after surgery (ventilation index score 19.5 +/- 6.5 vs 14.3
      +/- 2.5, P = 0.004); and received greater fluid administration (225 +/- 6 3 vs
      168 +/- 45 ml kg(-1), P = 0.002) in the first 48 postoperative hours. Despite
      these differences, infants with passive PD achieved negative fluid balance more
      rapidly (12 +/- 10 vs 27.3 +/- 13 h, P < 0.0001) and to a greater extent (-73 +
      55 vs +2.6 + 39 mL kg(-1) at 48 h, P = 0.002). Moreover, postoperative
      hemodynamics, urine output, creatinine clearance, blood urea nitrogen, peak
      lactate, and duration of mechanical ventilation were similar between groups.
      CONCLUSIONS: Passive PD is safe and promotes negative fluid balance after repair
      of complete AVSD without adversely affecting intravascular volume.

PMID- 21715182
TI  - Critical care nurses' opinion and self-reported practice of oxygen therapy: a
      survey.
AB  - BACKGROUND: Critical care nurses frequently and independently manage oxygen
      therapy. Despite the importance of oxygen therapy, there is limited evidence to
      inform or support critical care nurses' oxygen therapy practices. AIM: To
      establish if there is variability in oxygen therapy practices of critical care
      nurses and examine the degree of variability. METHOD: On-line questionnaire of
      ACCCN members between April and June 2010. RESULTS: The response rate was 36%
      (542/1523 critical care nurses). Overall, 378 (70%) respondents practiced in
      metropolitan critical care units; 278 (51%) had >=14 years of specialty practice.
      In response to falling SpO(2), 8.9% of nurses would never escalate oxygen therapy
      without a doctor's request, and 51% of nurses would not routinely escalate oxygen
      therapy in the absence of medical orders. Only 56% of nurses reported always
      increasing FiO(2) prior to endotracheal suctioning. In mechanically ventilated
      patients, 33% of nurses believed oxygen toxicity was a greater threat to lung
      injury than barotrauma. More than >60% of respondents reported a tolerance for a
      stable SpO(2) of 90%. Nurses in rural critical care units were less likely to
      independently titrate oxygen to their own target SpO(2), but more likely to
      independently treat a falling SpO(2) with higher FiO(2). CONCLUSION: Critical
      care nurses varied in their self-reported oxygen therapy practices justifying
      observational and interventional studies aimed at improving oxygen therapy for
      critically ill patients.

PMID- 21715183
TI  - Challenges in the current antiangiogenic treatment paradigm for patients with non
      small cell lung cancer.
AB  - Patients with non-small cell lung cancer (NSCLC) often present with advanced
      disease and cure rates are dismal with currently available treatment. Novel
      therapies including small molecule tyrosine kinase inhibitors and monoclonal
      antibodies are being developed to target angiogenesis, an essential step in
      tumorigenesis and metastasis. The only antiangiogenic agent currently approved
      for treatment of NSCLC is bevacizumab, although numerous other antiangiogenic
      inhibitors (e.g., sorafenib, sunitinib, cediranib, motesanib, BIBF 1120) are in
      clinical trials. Individualized treatment algorithms may improve patient outcomes
      and new evidence suggests that biomarkers may guide treatment decisions. We
      present an overview of the molecular pathways involved in angiogenesis, discuss
      clinical trials of bevacizumab and developmental antiangiogenic agents, and
      address the challenges of developing individualized treatment paradigms for
      NSCLC, particularly the use of biomarkers.

PMID- 21715184
TI  - Cytokine-like factor 1 (CLF1): life after development?
AB  - Cytokine-like factor 1 (CLF1) is a secreted receptor belonging to the interleukin
      6 family of cytokines. CLF1 and its physiologic partner, cardiotrophin-like
      cytokine (CLC) are secreted as a heterodimer and engage the tripartite signaling
      complex of ciliary neurotrophic factor receptor (CNTFR), leukemia inhibitory
      factor (LIFR) and gp130. Ligation of this receptor complex leads to activation of
      the STAT3 and MAPK pathways and mediates survival pathways in neurons. Mutations
      in CLF1, CLC, or CNTFR in mice lead to the birth of mice that die on post-natal
      day 1 because of an inability to nurse. These animals exhibit significant
      decreases in the number of motor neurons in the facial nucleus and the spinal
      cord. CLF1 or CLC deficiency is associated with the development of the human cold
      induced sweating syndromes. A growing body of research suggests that CLF1
      expression may be associated with several post-natal disease processes. In this
      review, we summarize the current understanding of CLF1 expression and suggest
      future studies to understand the potentially important role of CLF1 in postnatal
      life and disease.

PMID- 21715185
TI  - Systemic and hepatic vein galectin-3 are increased in patients with alcoholic
      liver cirrhosis and negatively correlate with liver function.
AB  - Recently we demonstrated higher galectin-3 in portal venous serum (PVS) compared
      to hepatic venous serum (HVS) in a small cohort of patients with normal liver
      function suggesting hepatic removal of galectin-3. Here, galectin-3 was measured
      by ELISA in PVS, HVS and systemic venous blood (SVS) of 33 patients with
      alcoholic liver cirrhosis and a larger cohort of 11 patients with normal liver
      function. Galectin-3 was cleared by the healthy but not the cirrhotic liver, and
      subsequently HVS and SVS galectin-3 levels were significantly increased in the
      patients with liver cirrhosis compared to controls. In healthy liver galectin-3
      was produced by cholangiocytes and synthesis by hepatocytes was only observed in
      cirrhotic liver. Hepatic venous pressure gradient did not correlate with galectin
      3 levels excluding hepatic shunting as the principal cause of higher SVS galectin
      3. Galectin-3 was elevated in all blood compartments of patients with CHILD-PUGH
      stage C compared to patients with CHILD-PUGH stage A, and was higher in patients
      with ascites than patients without this complication. Galectin-3 was negatively
      associated with antithrombin-3 whose synthesis is reduced with worse liver
      function. Galectin-3 positively correlated with urea and creatinine, and PVS
      galectin-3 showed a negative association with creatinine clearance as an accepted
      measure of kidney function. To summarize in the current study systemic, portal
      and hepatic levels of galectin-3 were found to be negatively associated with
      liver function in patients with alcoholic liver cirrhosis and this may in part be
      related to impaired hepatic removal and/or increased synthesis in cirrhotic
      liver.

PMID- 21715186
TI  - Biochemical and biological characteristics of cross-reacting material 197 CRM197,
      a non-toxic mutant of diphtheria toxin: use as a conjugation protein in vaccines
      and other potential clinical applications.
AB  - The biochemical and biological characteristics of CRM(197) are reviewed.
      Polysaccharide protein conjugate vaccines represent an important technological
      advancement that allowed for protection against dangerous diseases in vulnerable
      populations such as infants. The first carrier proteins, diphtheria and tetanus
      toxoids, were chosen in the context of an extensive body of information
      describing their immunogenicity and safety profiles in clinical use. These
      carriers perform well, and they require detoxification. A non-toxic mutant of
      diphtheria toxin, cross-reacting material 197 (CRM(197)), is a useful carrier
      protein with several manufacturing and other potential advantages over toxoids.
      For over a decade, several important and widely used routine childhood
      glycoconjugate vaccines against serious illnesses, including Haemophilus
      influenzae type b and pneumococcal disease, have employed CRM(197) as carrier
      protein. Additional clinical applications of CRM(197), as in chemotherapy, also
      exist.

PMID- 21715187
TI  - Intranodal lymphangiography: feasibility and preliminary experience in children.
AB  - PURPOSE: To review an initial experience studying the lymphatic system using
      direct injection of ethiodized oil contrast medium into lymph nodes (ie,
      intranodal lymphangiography) in children with chylous disorders. MATERIALS AND
      METHODS: Children with chylous disorders who underwent intranodal
      lymphangiography were included in this retrospective study. Under general
      anesthesia, ultrasonography was used to guide the placement of a small-bore (22
      25-gauge) needle into an inguinal lymph node. Ethiodized oil contrast medium was
      very slowly injected into the node. Opacification of the lymphatic system was
      documented with fluoroscopic and digital substraction imaging and
      videofluoroscopic clips. RESULTS: Five children (age range, 6 wk to 17 y) with
      chylous vaginorrhea (n = 1), postoperative chylothorax (n = 2), or spontaneous
      chylothorax (n = 2) underwent intranodal lymphangiography. The amount of
      ethiodized oil injected was 0.5-4.5 mL. Intranodal lymphangiography was
      successfully completed in four patients. One procedure was terminated because of
      patient motion and extravasation of contrast medium. Lymphangiographic findings
      included a spectrum of lymphatic channel disorders including incompetence,
      obstruction, collateralization, chylous reflux, and chylous leak. There were no
      complications. CONCLUSIONS: The simplified technique of injecting contrast medium
      into a lymph node to opacify the lymphatic system in children can be an
      alternative to the more elaborate conventional lymphangiography.

PMID- 21715188
TI  - Dealing with HIV-related stigma: a qualitative study of women outpatients from
      the Chris Hani Baragwanath Hospital.
AB  - HIV-related stigma is widely regarded as a key impediment to effective prevention
      and care. The purpose of this study was to explore HIV-infected women
      outpatients' experiences of stigma and the coping strategies that they devised to
      deal with it. Six HIV-infected women receiving antiretroviral treatment from the
      Nthabiseng Clinic of the Chris Hani Baragwanath Hospital participated in this
      qualitative study. HIV-related stigma was experienced by all the participants and
      was narrated as a sense of loss that gave rise to feelings of fear and shame. To
      cope with this, the women isolated themselves, became secretive about their
      health, disclosed strategically, and enlisted support. The elements of stigma and
      the coping strategies employed as uncovered in this study suggest a basis from
      which interventions aimed at assisting HIV-infected people to deal with stigma
      can be planned.

PMID- 21715189
TI  - Biologic prosthesis to prevent recurrence after laparoscopic paraesophageal
      hernia repair: long-term follow-up from a multicenter, prospective, randomized
      trial.
AB  - BACKGROUND: In 2006, we reported results of a randomized trial of laparoscopic
      paraesophageal hernia repair (LPEHR), comparing primary diaphragm repair (PR)
      with primary repair buttressed with a biologic prosthesis (small intestinal
      submucosa [SIS]). The primary endpoint, radiologic hiatal hernia (HH) recurrence,
      was higher with PR (24%) than with SIS buttressed repair (9%) after 6 months. The
      second phase of this trial was designed to determine the long-term durability of
      biologic mesh-buttressed repair. METHODS: We systematically searched for the 108
      patients in phase I of this study to assess current clinical symptoms, quality of
      life (QOL) and determine ongoing durability of the repair by obtaining a follow
      up upper gastrointestinal series (UGI) read by 2 radiologists blinded to
      treatment received. HH recurrence was defined as the greatest measured vertical
      height of stomach being at least 2 cm above the diaphragm. RESULTS: At median
      follow-up of 58 months (range 42 to 78 mo), 10 patients had died, 26 patients
      were not found, 72 completed clinical follow-up (PR, n = 39; SIS, n = 33), and 60
      repeated a UGI (PR, n = 34; SIS, n = 26). There were 20 patients (59%) with
      recurrent HH in the PR group and 14 patients (54%) with recurrent HH in the SIS
      group (p = 0.7). There was no statistically significant difference in relevant
      symptoms or QOL between patients undergoing PR and SIS buttressed repair. There
      were no strictures, erosions, dysphagia, or other complications related to the
      use of SIS mesh. CONCLUSIONS: LPEHR results in long and durable relief of
      symptoms and improvement in QOL with PR or SIS. There does not appear to be a
      higher rate of complications or side effects with biologic mesh, but its benefit
      in reducing HH recurrence diminishes at long-term follow-up (more than 5 years
      postoperatively) or earlier.

PMID- 21715191
TI  - "Sex isn't something you do with someone you don't care about": young women's
      definitions of sex.
AB  - STUDY OBJECTIVE: How young women define sexual intercourse has implications for
      their sexually transmitted infection (STI) risk. This study investigated young
      women's (1) definitions of sex, (2) understanding of a unique sex event, and (3)
      definitions of when a sex event begins and ends. DESIGN: Using semi-structured
      interviews, young women were asked to define sex, define when a sex event began
      and ended, and were asked whether they thought their partners would agree.
      Interview transcripts were analyzed using thematic analysis. SETTING:
      Participants were recruited from an urban adolescent health clinic in the
      Northeastern United States. PARTICIPANTS: Twenty-four heterosexual, sexually
      active young women contributed data for analysis. INTERVENTIONS: None. RESULTS:
      Young women's definitions of sex varied. Some included anal and oral sex while
      others did not. Time between sex events, new condom use, and new erection were
      used to define unique sex events. Some believed sex began with foreplay. Others
      believed sex began when the penis entered the vagina. Some believed sex ended
      when the penis was withdrawn from the vagina. Others believed sex ended with
      orgasm for one or both partners. Young women talked about the influence of
      relationship type on their definitions of sex. CONCLUSIONS: Variations in young
      women's definitions of sex may influence their responses to clinical questions
      about sexual activity and their understanding of their STI risk. As such, our
      findings have important implications for clinical counseling regarding sexual
      behavior and correct condom use and for researchers investigating young women's
      sexual behavior.

PMID- 21715192
TI  - Laparoscopic treatment of ovarian cysts in adolescents and young adults.
AB  - STUDY OBJECTIVE: To investigate the laparoscopic management of ovarian cysts in
      adolescents and young adults. DESIGN: A retrospective chart review study.
      SETTING: Zekai Tahir Burak Women's Health Research and Education Hospital.
      PARTICIPANTS: A total of 282 females aged 25 years or younger underwent
      laparoscopic surgery for a presumed benign ovarian cyst. Patients were grouped as
      adolescents (ages 12-19, n = 79) or young adults (ages 20-25, n = 203). MAIN
      OUTCOME MEASURES: Surgical approach, operative findings and the correlation of
      intraoperative diagnosis with the definitive pathological reports. RESULTS: The
      mean age of the patients was 21.2 years. At laparoscopic surgery, 89 patients
      (31.6%) had endometriomas, 47 (16.7%) had dermoid cysts, and 37 (13.1%) had
      paraovarian cysts. Ninety-seven patients (34.4%) had simple ovarian cysts.
      Pathological reports revealed that young adults were more likely to have
      endometriomas (34.0% vs 7.6%, P < 0.01), but dermoid cysts and simple ovarian
      cysts were more frequent (20.3% vs 15.3%, P < 0.01 and 60.7% vs 40.9%, P < 0.01,
      respectively).in adolescents. Eleven of the cases (3.9%) were found to have
      mucinous cystadenomas and fourteen (5.0%) to have serous cystadenomas. Four cysts
      were malignant (1.4%). Cystectomy was performed in 205 cases (72.7%),
      fenestration of cyst wall was performed in 53 cases (18.8%), and aspiration was
      applied in 22 cases (7.8%). The types of operation were not significantly
      different among adolescents and young adults (P > 0.05). The operative diagnosis
      was highly correlated with the final pathological reports (kappa value= 0.901, P
      < 0.001). There were no operative and postoperative complications in our series.
      CONCLUSION: With a careful preoperative screening, the laparoscopic surgery of
      ovarian cyst is an efficient and safe treatment for adolescents and young adults.

PMID- 21715193
TI  - Hysteroscopic resection of a symptomatic uterine leiomyoma in an adolescent.
AB  - BACKGROUND: Uterine leiomyomas or fibroids are rare in the adolescent population.
      Hysteroscopic resection is an ideal approach for adolescents with symptomatic
      intracavitary myomas. CASE: A 17-year-old female had a history of
      menometrorrhagia and symptomatic anemia, and had been hospitalized twice for
      acute management of heavy bleeding. On pelvic ultrasound and subsequent MRI, a 2
      * 3 cm mass was visualized and appeared to distort the uterine cavity. Due to
      recurrent heavy bleeding, operative hysteroscopy was performed, and a 3-cm
      intracavitary mass was identified and resected; pathology evaluation confirmed a
      leiomyoma. SUMMARY AND CONCLUSION: Surgical intervention for abnormal bleeding
      due to a submucosal myoma was more successful than medical treatment. In
      adolescents, hysteroscopic resection of a symptomatic submucosal myoma is a
      reasonable minimally invasive management option.

PMID- 21715194
TI  - A rare vulvar manifestation of neurofibromatosis 1 in a teen.
AB  - Neurofibromatosis 1 is an autosomal dominant disorder with cutaneous findings
      that include multiple cafe-au-lait spots, axillary/inguinal freckling, dermal,
      and plexiform neurofibromas. Skin manifestations, including involvement of the
      vulva, are often the most troubling physical finding to patients. Hormonal and
      growth factor changes during puberty have been implicated in neurofibroma growth.
      In the case presented here, an exceedingly rare isolated vulvar neurofibroma
      without clitoral involvement became enlarged and symptomatic, requiring
      excisional surgery after puberty. The diffuse involvement of these tumors makes
      complete resection very difficult and recurrence is common.

PMID- 21715195
TI  - Idiopathic pulmonary hypertension causing acquired von Willebrand disease and
      menorrhagia.
AB  - BACKGROUND: Von Willebrand disease (VWD) maybe inherited or acquired; both
      etiologies can be associated with heavy menstrual bleeding. Pulmonary arterial
      hypertension may result in acquired VWD due to the destruction of high molecular
      weight von Willebrand multimers. We report a case of menorrhagia due to acquired
      VWD in a patient with idiopathic pulmonary hypertension. CASE: An adolescent
      female with known idiopathic pulmonary hypertension developed acquired VWD. Her
      primary disease necessitates the use of platelet inhibitors and intermittent
      anticoagulation. At menarche she also developed menorrhagia due to acquired VWD.
      She is currently controlled with stimate and progesterone-only therapy. VWD in a
      patient with idiopathic pulmonary hypertension causing menorrhagia. Although VWD
      and menorrhagia are commonly linked, the treatment and disease process in a
      patient with idiopathic pulmonary arterial hypertension is incredibly complex.

PMID- 21715196
TI  - Seasonal trends in adolescent pregnancy conception rates.
AB  - STUDY OBJECTIVE: The objectives of this study were to determine if a seasonal
      trend exists in adolescent pregnancies and to compare the teen conception rate
      per month to an adult population. SETTING: The study was conducted in a tertiary
      care Canadian hospital that has a one-site model of care. DESIGN: A retrospective
      chart review of all adolescent pregnancies over a 5-year period (N = 838) was
      undertaken. From the 13,554 adult pregnancies over the same time period, a random
      sample of 838 pregnancies was chosen for similar chart review. A chi-square test
      was used to compare the proportion of pregnancies conceived in each calendar
      month between the two groups. PARTICIPANTS: Pregnancies ending in spontaneous
      abortions, elective terminations, ectopic pregnancies, as well as obstetrical
      deliveries, were included. RESULTS: There was a significantly different monthly
      trend seen in adolescent pregnancy conceptions when compared with the adult group
      (chi2 = 24.38, df = 11, P = 0.0112). The adolescent group was observed to have a
      unique peak in the number of pregnancies conceived in March (10.5% of pregnancies
      conceived compared to 7.3% in adults). In addition, 8.5% of conceptions in
      adolescents occurred in December compared to 10.4% in adults. CONCLUSIONS: There
      are several plausible explanations for the modest but real differences identified
      in this study including trends in fecundity/fertility or social/school events
      that lead to increased sexual activity. Peaks in conception indicate times when a
      greater need for health care services exists, and when preventive education can
      be most effective.

PMID- 21715197
TI  - Fertility outcomes subsequent to treatment of tubal ectopic pregnancy in younger
      Turkish women.
AB  - STUDY OBJECTIVE: The assessment of future fertility in patients that were
      hospitalized with diagnosis of tubal ectopic pregnancy. DESIGN: Between January
      1998 and September 2008, we retrospectively reviewed 219 tubal ectopic pregnancy
      patients who were hospitalized. The patients using contraceptive methods,
      underwent previous pelvic or tubal surgery, pregnancy after in vitro
      fertilization, over the age of 28, and extratubal ectopic pregnancies were
      excluded. Patients who actively attempted to conceive were included. We called
      all the patients to see whether they had pregnancy in 24 months, and how long
      they had waited for this after the operation. Overall, we could not reach 14
      patients who were treated surgically (n = 9) or medically (n = 5). SETTING:
      Department of Obstetrics and Gynecology, Ege University, Izmir, Turkey.
      PARTICIPANTS: Women aged between 18 and 28 years that were treated because of
      tubal ectopic pregnancy and have concerns about infertility. INTERVENTIONS:
      Medical treatment with methotrexate (n = 34), salpingectomy (n = 62)
      salpingostomy (n = 37). MAIN OUTCOME MEASURES: Intrauterine pregnancy rates,
      ectopic pregnancy rates and mean time to pregnancy after interventions. RESULTS:
      After questionnaire: in the methotrexate group; six of 29 (20%) had no pregnancy;
      23 (79%) of them conceived, but three (10%) of the pregnancies were extrauterine.
      Thirty-seven patients received salpingostomy and 62 patients composed the
      salpingectomy group. Intrauterine pregnancy rates up to 24 months were
      established as 65.2% in salpingectomy (n = 55) and 60.1% in the salpingostomy (n
      = 35) groups respectively. No significant difference was noticed when pregnancy
      rates were compared among three groups (P = 0.942). Mean time to pregnancy in
      methotrexate group was 7.8 +/- 2.2 months, and in salpingostomy and salpingectomy
      groups was 8.7 +/- 2.2 and 9.3 +/- 3.1 months respectively (P = 0.841).
      CONCLUSION: Since we found no difference in terms of pregnancy rates among three
      groups, medical treatment appears to be more favored with early and accurate
      diagnosis. After salpingectomy, patients may conceive later in life when compared
      with other groups so selected patients should be assessed according to their age
      for the decision of assisted reproductive techniques.

PMID- 21715198
TI  - Mother-daughter communication and college women's confidence to communicate with
      family members and doctors about the human papillomavirus and sexual health.
AB  - STUDY OBJECTIVE: In this study, we examined whether mother-daughter sexuality
      communication in midadolescence contributes to young women's self-efficacy to
      consult with family members about sexual health problems, and to talk with
      physicians about the human papillomavirus (HPV). PARTICIPANTS AND SETTING: Young
      European American, Latina, and Asian Pacific Islander college women reported on
      how confident they felt talking to their family members and doctors about HPV and
      sexual health issues. MAIN OUTCOME MEASURES: We gathered retrospective data
      regarding the nature of mother-daughter communication, including sexuality
      communication, in midadolescence. Other variables included physician trust,
      knowledge about HPV, and reports of current sexual activity. RESULTS: More
      openness in past general communication with their mothers, more perceived comfort
      in past sexuality communication, and a greater number of reproductive health
      topics discussed was linked to greater confidence in communicating with family
      members about sexual health problems. In addition, higher levels of sexual
      activity, more knowledge about HPV, and the number of reproductive health topics
      discussed with mothers in midadolescence, were associated with increased
      confidence talking to doctors about HPV and sexual health. CONCLUSION: Positive
      communication experiences with mothers in the early years may reduce the shame,
      embarrassment, and anxiety associated with talking to physicians about sensitive
      sexuality issues.

PMID- 21715199
TI  - Urodynamic and haemodynamic effects of a single oral administration of ephedrine
      or phenylpropanolamine in continent female dogs.
AB  - This study investigated the effects of a single oral administration of ephedrine
      (2 mg/kg) or phenylpropanolamine (PPA) (1.5 mg/kg) on the vesico-urethral and
      cardiovascular functions in continent female dogs. Urethral pressure profilometry
      (UPP), arterial blood pressures and heart rate were measured in five control dogs
      and after single-dose treatment with ephedrine or PPA at T(0), T(2h), T(4h),
      T(6h), T(12h), T(18h) and T(24h). UPPs were performed under propofol anaesthesia
      and other measurements were performed on awake dogs. A telemetric urodynamic
      investigation was performed on three additional dogs for 24 h after the
      administration of each drug. Urethral pressures increased over 4-6 h and urethral
      functional lengths increased 2-6h after administration of both drugs. During
      micturition, a decrease in detrusor pressure coupled with an increase in bladder
      volume was observed after ephedrine administration and there was also an increase
      in bladder volume after PPA had been given. With both drugs increased arterial
      blood pressures at 4-6 h were compensated by a decreased heart rate over 12 h.
      Urethral function was improved after both ephedrine and PPA, and bladder function
      also improved during micturition following ephedrine.

PMID- 21715200
TI  - Are there gender differences in coping with neck pain following acute whiplash
      trauma? A 12-month follow-up study.
AB  - BACKGROUND: Little is known about gender differences in coping after whiplash,
      and to date possible interaction of gender and coping on recovery has not been
      investigated. AIMS: To examine if gender differences in coping are associated
      with long-lasting neck pain after acute whiplash. Seven hundred and forty
      participants referred from emergency departments or general practitioners after
      car accidents in Denmark. Within a median of five days, post-collision
      participants completed questionnaires on collision characteristics, psychological
      distress, and socio-demographics. After 3 months they completed the Coping
      Strategies Questionnaire, and after 12 months a VAS scale on neck pain intensity.
      RESULTS: The odds for long-lasting neck pain were more than twice as high for
      women than for men (OR = 2.17 (95% CI: 1.40; 3.37). However, no gender difference
      in coping and no interaction between gender and the five coping subscales on neck
      pain after 12 months were found. 'Distraction' increased the odds for
      considerable neck pain for both men and women (OR = 1.03 (95% CI: 1.01; 1.05),
      'reinterpreting' (OR = 1.03 (95% CI: 1.01; 1.06), 'catastrophizing' (OR = 1.14
      (95% CI: 1.10; 1.18), and 'praying and hoping' (OR = 1.10 (95% CI: 1.05; 1.13)
      for each point on these scales. CONCLUSIONS: No interaction between coping and
      gender on neck pain was found, thus different coping strategies 3 months post
      collision did not explain the different prognosis observed in men and women.
      Clinically relevant influence of 'catastrophizing' and 'praying and hoping' to
      prognosis was found, therefore we should identify patients predominantly using
      these strategies.

PMID- 21715201
TI  - Multiple decoherence-free states in multi-spin systems.
AB  - A numerical procedure is presented for mapping the vicinity of the null-space of
      the spin relaxation superoperator. The states populating this space, i.e. those
      with near-zero eigenvalues, of which the two-spin singlet is a well-studied
      example, are long-lived compared to the conventional T(1) and T(2) spin
      relaxation times. The analysis of larger spin systems described herein reveals
      the presence of a significant number of other slowly relaxing states. A study of
      coupling topologies for n-spin systems (4<=n<=8) suggests the symmetry
      requirements for maximising the number of long-lived states.

PMID- 21715202
TI  - An extrapolation method for computing protein solvation energies based on density
      fragmentation of a graphical surface tessellation.
AB  - Modeling chemical events inside proteins often require the incorporation of
      solvent effects via continuum polarizable models. One of these approaches is
      based on the assumption that the interface between solute and solvent acts as a
      conductor. Image charges are added on the molecular surface to satisfy the
      appropriate conductor boundary conditions in the presence of solute charges. As
      in the case of other polarizable continuum models that are based on surface
      tessellation, the simplest implementation of this approach is often limited to
      several hundred atoms due to a matrix inversion, which scales as the cube of the
      number or tesserae. For larger systems, approaches that use iterative matrix
      solvers coupled to fast summation methods must be used. In the present work, we
      develop a self-consistent approach to obtain conductor-like screening charges
      suitable for applications in proteins. The approach is based on a density
      fragmentation of a graphical surface tessellation. This method, although
      approximate, provides a straightforward scheme of parallelization, which can in
      principle be added to existing linear scaling implementations of conductor-like
      models. We implement this method in conjunction with a fixed charge model for the
      protein, as well as with a moving domain QM/MM description of the protein. In the
      latter case, the overall result leads to a charge distribution within the protein
      determined by self-polarization and polarization due to solvent.

PMID- 21715203
TI  - The effect of beta-saturated pyrrolic rings on the electronic structures and
      aromaticity of magnesium porphyrin derivatives: a density functional study.
AB  - Density functional theory (DFT) calculation on the molecular structures,
      molecular orbitals, electronic absorption spectra, and magnetic properties of
      magnesium porphyrin (MgPor) and a series of five hydrogenated magnesium porphyrin
      complexes with different number of beta-saturated pyrrolic rings, namely MgPor
      beta-1Hy, MgPor-beta-opp-2Hy, MgPor-beta-adj-2Hy, MgPor-beta-3Hy, and MgPor-beta
      4Hy, clarifies the red-shift of the lowest energy absorption band from
      chlorophyll a to bacteriochlorophyll and reveals the strong chemical stability
      for both of them. The energy levels of highest occupied molecular orbitals (HOMO)
      and HOMO-1 for MgPor are reversed upon hydrogenation at beta-positions (2 and 3,
      7 and 8, 12 and 13, and 17 and 18) of porphyrin ring. Along with the increase of
      beta-saturated pyrrolic rings from 1, 2, 3, to 4, the HOMO energy increases from 
      4.78 eV to -3.10 eV in a regular manner. In contrast, the lowest unoccupied
      molecular orbitals (LUMO) energy levels of MgPor, MgPor-beta-1Hy, and MgPor-beta
      opp-2Hy are very similar with each other. As a result, the lowest energy
      absorption band involving main transition from HOMO to LUMO is red-shifted from
      MgPor-beta-1Hy to MgPor-beta-opp-2Hy which is representative of chlorophyll a and
      bacteriochlorophyll, respectively. Natural hydroporphyrins represented by MgPor,
      MgPor-beta-1Hy, and MgPor-beta-opp-2Hy have turned out to be aromatic and stable
      enough, in good accordance with the ubiquity of their derivatives in the nature.
      In contrast, MgPor-beta-adj-2Hy, MgPor-beta-3Hy, and MgPor-beta-4Hy with
      relatively weak aromaticity seem to be unstable and therefore were not found in
      nature.

PMID- 21715204
TI  - [Acyclovir-induced acute renal failure in a paediatric oncology patient].

PMID- 21715205
TI  - [Silver nitrate-albumin complex for endoscopic treatment of bronchopleural
      fistula].

PMID- 21715206
TI  - Adjunctive therapy with interferon-gamma for the treatment of pulmonary
      tuberculosis: a systematic review.
AB  - OBJECTIVE: To evaluate the efficacy and safety of adjunctive therapy using
      interferon-gamma (IFN-gamma; an immunomodulator) for the treatment of pulmonary
      tuberculosis (TB). METHODS: We conducted a systematic review of controlled
      clinical trials that compared anti-TB drugs in combination with IFN-gamma with
      the same anti-TB drugs alone for the treatment of pulmonary TB. RESULTS: Nine
      trials were identified, with IFN-gamma being aerosolized or administered
      subcutaneously in one trial, aerosolized only in five trials, and administered
      intramuscularly in three trials. The methodology quality of all trials was rated
      'C'. Meta-analysis of the trials with aerosolized IFN-gamma showed statistical
      benefits on sputum negative conversion and chest radiograph: the pooled relative
      risk (RR) for conversion was 1.97 (95% confidence interval (CI) 1.20-3.24,
      p=0.008) after 1 month of treatment, 1.74 (95% CI 1.30-2.34, p=0.0002) after 2
      months of treatment, 1.53 (95% CI 1.16-2.01, p=0.003) after 3 months of
      treatment, 1.57 (95% CI 1.20-2.06, p=0.001) after 6 months of treatment, and 1.55
      (95% CI 1.17-2.05, p=0.002) at the end of treatment; the pooled RR for the chest
      radiograph was 1.38 (95% CI 1.10-1.17, p=0.006) at the end of treatment. For
      intramuscularly administered IFN-gamma, meta-analysis of three trials showed its
      significant improvement on sputum negative conversion after 2 months of
      treatment. A randomized controlled trial with aerosolized and subcutaneously
      administered IFN-gamma reported significant reductions in the symptoms of fever,
      wheeze, and night sweats in the IFN-gamma-treated groups compared with the
      control group after 1 month of treatment. No patients discontinued treatment
      because of adverse effects caused by IFN-gamma. CONCLUSION: Adjuvant therapy
      using IFN-gamma, especially by aerosol, might be beneficial to TB patients, but
      large randomized controlled trials are needed for further evaluation of its
      efficacy and safety considering the quality of the trials analyzed.

PMID- 21715207
TI  - Pattern and etiology of culture-proven early-onset neonatal sepsis: a five-year
      prospective study.
AB  - OBJECTIVES: To investigate the incidence of early-onset neonatal sepsis and
      identify the main pathogens over a 5-year period in Kuwait. METHODS: Blood
      samples were collected from all infants with any clinical or laboratory feature
      suggestive of sepsis, at the main maternity hospital in Kuwait. Cases of early
      onset neonatal infection were defined as culture of a single potentially
      pathogenic organism from blood or cerebrospinal fluid from infants younger than 7
      days of age, in association with clinical or laboratory findings consistent with
      infection. RESULTS: The overall incidence of early-onset neonatal infection was
      2.7 (95% confidence interval (CI) 2.3-3.2) episodes per 1000 live-births. The
      case-fatality was 13.1% (95% CI 8.6-18.9%). Group B Streptococcus (GBS) accounted
      for 17.6% of infections among infants younger than 7 days (incidence 0.48 per
      1000 live-births), but 38.1% of infections in the first 2 days of life. Neither
      the incidence of early-onset infection by GBS nor by Escherichia coli changed
      significantly over the study period. CONCLUSIONS: Although the incidence of GBS
      infections was relatively low, GBS accounted for most early-onset infections.
      Intrapartum antibiotic prophylaxis against GBS should be strengthened. There was
      no evidence to suggest that early-onset infection due to non-GBS organisms such
      E. coli has increased in the last 5 years.

PMID- 21715208
TI  - [Pathogen reduction: a clinician view].

PMID- 21715209
TI  - [Pathogen reduction for platelets: a debate].

PMID- 21715210
TI  - [Pathogen inactivation processes applicable to cellular products: the Canadian
      perspective].
AB  - The highlights of the recent Canadian consensus conference on pathogen
      inactivation are summarized. Also, a brief summary of steps taken to date in
      order to implement these technologies is presented.

PMID- 21715211
TI  - Non-invasive and quantitative assessment of sudomotor function for peripheral
      diabetic neuropathy evaluation.
AB  - AIMS: Perturbation of pain sensation is considered one of the major initiating
      risk factors for diabetic foot ulcer. Sweat dysfunction leading to abnormal skin
      conditions, including dryness and fissures, can increase foot ulcer risk. The aim
      of this study was to evaluate SudoscanTM, a new, quick, non-invasive and
      quantitative method of measuring sudomotor dysfunction as a co-indicator of the
      severity of diabetic polyneuropathy (DPN). METHODS: A total of 142 diabetic
      patients (age 62+/-18 years, diabetes duration 13+/-14 years, HbA(1c) 8.9+/-2.5%)
      were measured for vibration perception threshold (VPT), using a biothesiometer,
      and for sudomotor dysfunction, using electrochemical sweat conductance (ESC)
      based on the electrochemical reaction between sweat chloride and electrodes in
      contact with the hands and feet. Retinopathy status was also assessed, as well as
      reproducibility between two ESC measurements and the effect of glycaemia levels.
      RESULTS: ESC measurements in the feet of patients showed a descending trend from
      66+/-17 MUS to 43+/-39 MUS, corresponding to an ascending trend in VPT threshold
      from <15 V to >25 V (P=0.001). Correlation between VPT and ESC was -0.45
      (P<0.0001). Foot ESC was lower in patients with fissures, while VPT was
      comparable. Both VPT and foot ESC correlated with retinopathy status. Bland
      Altman plots indicated good reproducibility between two measurements, and between
      low and high glycaemia levels. CONCLUSION: SudoscanTM is a reproducible technique
      with results that are not influenced by blood glucose levels. Sweating status may
      be a quantitative indicator of the severity of polyneuropathy that may be useful
      for the early prevention of foot skin lesions.

PMID- 21715212
TI  - Novel modified ultrasonication technique for the extraction of lycopene from
      tomatoes.
AB  - Lycopene extraction was carried out via the ultrasonic assisted extraction (UAE)
      with response surface methodology (RSM). Sonication enhanced the efficiency of
      relative lycopene yield (enhancement of 26% extraction yield of lycopene in 6
      replications at 40.0 min, 40.0  degrees C and 70.0% v/w in the presence of
      ultrasound), lowered the extraction temperature and shortened the total
      extraction time. The extraction was applied with the addition of oxygen-free
      nitrogen flow and change of water route during water bath sonication. The highest
      relative yield of lycopene obtained was 100% at 45.0  degrees C with total
      extraction time of 50.0 min (30:10:10) and ratio of solvent to freeze-dried
      tomato sample (v/w) of 80.0:1. Optimisation of the lycopene extraction had been
      performed, giving the average relative lycopene yield of 99% at 45.6 min, 47.6 
      degrees C and ratio of solvent to freeze-dried tomato sample (v/w) of 74.4:1.
      From the optimised model, the average yield of all-trans lycopene obtained was
      5.11+/-0.27 mg/g dry weight. The all-trans lycopene obtained from the high
      performance liquid chromatography (HPLC) chromatograms was 96.81+/-0.81% with
      3.19+/-0.81% of cis-lycopenes. The purity of total-lycopene obtained was 98.27+/
      0.52% with beta-carotene constituted 1.73+/-0.52% of the extract. The current
      improved, UAE of lycopene from tomatoes with the aid of RSM also enhanced the
      extraction yield of trans-lycopene by 75.93% compared to optimised conventional
      method of extraction. Hence, the current, improved UAE of lycopene promotes the
      extraction yield of lycopene and at the same time, minimises the degradation and
      isomerisation of lycopene.

PMID- 21715213
TI  - What motivates Parkinson's disease patients to enter clinical trials?
AB  - INTRODUCTION: Limited data is available regarding motivations and concerns of
      Parkinson's disease (PD) patients when participating in clinical trials (CTs).
      Knowledge of these factors may improve the recruitment and quality of future
      trials. OBJECTIVES: To assess the motivations and concerns of PD patients
      concerning participation in CTs and to evaluate the extent to which patients
      understand informed consent materials and placebo effect concept. METHODS: Cross
      sectional study in PD patients enrolled in CTs between 2002 and 2007. Two
      questionnaires designed for placebo-controlled and active-controlled studies were
      mailed to patients. RESULTS: From the 93/127 replied questionnaires (response
      rate: 73.2%) 91 were evaluable. Fifty-nine percent of the participants were women
      with a mean age of 66.8 years. The main reasons for participating in CTs were to
      help the advance of science (63.7%), to gain access to a better treatment
      (56.0%), and to benefit others (51.6%). Risk of adverse events (49.5%) and
      negative effects of treatment (35.2%) were the major concerns. Ninety percent
      reported they had understood the informed consent. Of 80 patients included in
      placebo-controlled studies, 63.9% understood the placebo effect concept.
      Globally, 66% of patients would participate in another CT and 41.6% in a placebo
      controlled trial. CONCLUSIONS: The main motivations of PD patients to participate
      in CTs were the benefit to the patient himself and to others. The major concern
      was safety. PD patients understood the informed consent, but more educational
      efforts must be made to explain the placebo effect. Most PD patients were very
      positive toward CTs and would participate in another trial.

PMID- 21715214
TI  - Brachytherapy seed reconstruction with joint-encoded C-arm single-axis rotation
      and motion compensation.
AB  - C-arm fluoroscopy images are frequently used for qualitative assessment of
      prostate brachytherapy. Three-dimensional seed reconstruction from C-arm images
      is necessary for intraoperative dosimetry and quantitative assessment. Seed
      reconstruction requires accurately known C-arm poses. We propose to measure the C
      arm rotation angles and computationally compensate for inevitable C-arm motion to
      compute the pose. We compensate the translational motions of a C-arm, such as
      oscillation, sagging and wheel motion using a three-level optimization algorithm
      and obviate the need for full pose tracking using external trackers or fiducials.
      We validated our approach on simulated and 100 clinical data sets from 10
      patients and gained on average, a seed matching rate of 98.5%, projection error
      of 0.33 mm (STD=0.21 mm) and computation time of 19.8s per patient, which must be
      considered as clinically excellent results. We also show that without motion
      compensation the reconstruction is likely to fail.

PMID- 21715215
TI  - A new classification for potentially malignant disorders of the oral cavity.

PMID- 21715216
TI  - Synthesis and spectroscopic studies on charge-transfer molecular complexes formed
      in the reaction of imidazole and 1-benzylimidazole with sigma- and pi-acceptors.
AB  - The spectrophotometric characteristics of the solid charge-transfer molecular
      complexes (CT) formed in the reaction of the electron donors imidazole (IML) and
      1-benzylimidazole (BIML) with the sigma-acceptor iodine and pi-acceptors 2,3
      dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), tetracyanoethylene (TCNE) and
      2,3,5,6-tetrachloro-1,4-benzoquinone (CHL) have been studied in chloroform at 25 
      degrees C. These were investigated through electronic and infrared spectra as
      well as elemental analysis. The results show that the formed solid CT-complexes
      have the formulas [(IML)2 I]I3, [(IML)(DDQ)], [(IML)2(TCNE)5] and [(IML)(CHL)]
      for imidazole and [(BIML) I]I3, [(BIML)(DDQ)2], [(BIML)(TCNE)2] and
      [(BIML)(CHL)2] for 1-benzylimidazole in full agreement with the known reaction
      stoichiometries in solution as well as the elemental measurements. The formation
      constant KCT, molar extinction coefficient ECT, free energy change DeltaG0, CT
      energy ECT and ionization potential Ip have been calculated for the CT-complexes
      [(IML)2 I]I3, [(IML)(DDQ)], [(IML)(CHL)], [(BIML) I]I3, [(BIML)(DDQ)2],
      [(BIML)(TCNE)2] and [(BIML)(CHL)2].

PMID- 21715217
TI  - Library of UV-Vis-NIR reflectance spectra of modern organic dyes from historic
      pattern-card coloured papers.
AB  - An accurate characterisation of the organic dyes used in artworks, especially
      those made of paper, is an important factor in designing safe conservation
      treatments. In the case of synthetic organic dyes used in modern works of art,
      for example, one frequently encountered difficulty is that some of these dyes are
      not still commercially available. Recognizing this problem, the authors of this
      paper present the results of an analysis of UV-Vis-NIR fibre optic reflectance
      spectra of 82 samples of dyed paper prepared with 41 dyes. The samples come from
      a historic book, The Dyeing of Paper in the Pulp, which was published by
      Interessen-Gemeinschaft (I.G.) Farbenindustrie in 1925. The dyes used in the
      paper pulp belong to the azo compounds, acridine, anthraquinone, azine,
      diphenylmethane, indigoid, methine, nitro, quinoline, thiazine, triphenylmethane,
      sulphur and xanthene classes.

PMID- 21715218
TI  - Fluorescence quenching of biologically active carboxamide by aniline and carbon
      tetrachloride in different solvents using Stern-Volmer plots.
AB  - Fluorescence quenching of biologically active carboxamide namely (E)-2-(4
      chlorobenzylideneamino)-N-(2-chlorophenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3
      carboxamide [ECNCTTC] by aniline and carbon tetrachloride (CCl4) quenchers in
      different solvents using steady state method and time resolved method using only
      one solvent has been carried out at room temperature to understand the role of
      quenching mechanisms. The Stern-Volmer plot has been found to be linear for all
      the solvents studied. The probability of quenching per encounter p (p') was
      determined in all the solvents and was found to be less than unity. Further, from
      the studies of rate parameters and life time measurements in n-heptane and
      cyclohexane with aniline and carbon tetrachloride as quenchers have been shown
      that, the phenomenon of quenching is generally governed by the well-known Stern
      Volmer (S-V) plot. The activation energy Ea (or E'a) of quenching was determined
      using the literature values of activation energy of diffusion Ed and the
      experimentally determined values of p (or p'). It has been found that, the
      activation energy Ea (E'a) is greater than the activation energy for diffusion Ed
      in all solvents. Hence, from the magnitudes of Ea (or E'a) as well as p (or p')
      infer that, the quenching mechanism is not solely due to the material diffusion,
      but there is also contribution from the activation energy.

PMID- 21715219
TI  - 2-Chloro- and 2-bromo-3-pyridinecarboxaldehydes: structures, rotamers, fermi
      resonance and vibration modes.
AB  - FT-Infrared (4000-400 cm(-1)) and NIR-FT-Raman (4000-50 cm(-1)) spectral
      measurements have been made for 2-chloro- and 2-bromo-3-pyridinecarboxaldehydes.
      A DFT vibration analysis at B3LYP/6-311++G (d,p) level, valence force-fields and
      vibrational mode calculations have been performed. Aided by very good agreement
      between observed and computed vibration spectra, a complete assignment of
      fundamental vibration modes to the observed absorptions and Raman bands has been
      proposed. Orientations of the aldehydic group have produced two oblate asymmetric
      rotamers for each molecule, ON-trans and ON-cis: the ON-trans rotamer being more
      stable than cis by 3.42 kcal mol(-1) for 2-chloro-3-pyridinecarboxaldehyde and
      3.68 kcal mol(-1) for 2-bromo-3-pyridinecarboxaldehyde. High potential energy
      barrier ca 14 kcal/mol, induced by steric hindrance, restricts rotamers'
      population to ON-trans only. It is observed that, in the presence of bromine, C-H
      stretching modes are pronounced; a missing characteristic ring mode in chlorine's
      presence shows at 1557 cm(-1); the characteristic ring mode at 1051 cm(-1) is
      diminished; a mixed mode near 707 cm(-1) is enhanced. Further, an observed
      doublet near 1696-1666 cm(-1) in both IR and Raman spectra is explained on the
      basis of Fermi resonance between aldehydic carbonyl stretching at 1696 cm(-1) and
      a combination mode of ring stretch near 1059 cm(-1) and deformation vibration,
      625 cm(-1). A strong Raman aldehydic torsional mode at 62 cm(-1) is interpreted
      to correspond to the dominant ON-trans over cis rotamers population.

PMID- 21715220
TI  - Discrimination of Radix Pseudostellariae according to geographical origins using
      NIR spectroscopy and support vector data description.
AB  - Near infrared (NIR) spectroscopy combined with support vector data description
      (SVDD) was attempted to identify geographical origins of Radix Pseudostellariae.
      Original spectra of eggs in wavelength range of 10000-4000 cm(-1) were acquired.
      SVDD was performed to calibrate discrimination model, and some parameters of SVDD
      model were optimized. Meanwhile, conversional two-class classification method
      support vector machine (SVM) was used comparatively for classification. Compared
      with SVM classification, SVDD model showed its superior ability in dealing with
      imbalance training samples. When the proportion of the number of Radix
      Pseudostellariae from Anhui province (the area where genuine crude Radix
      Pseudostellariae was cultivated) and other provinces was one to sixteen, the
      identification rate of SVDD model was 92.5% in prediction set. This work
      indicates that NIR spectroscopy combined with SVDD is an excellent choice in
      building one-class calibration model for discrimination of genuine crude Radix
      Pseudostellariae.

PMID- 21715221
TI  - Synthesis, spectroscopic studies and crystal structure of the Schiff base ligand
      L derived from condensation of 2-thiophenecarboxaldehyde and 3,3'
      diaminobenzidine and its complexes with Co(II), Ni(II), Cu(II), Cd(II) and
      Hg(II): Comparative DNA binding studies of L and its Co(II), Ni(II) and Cu(II)
      complexes.
AB  - The Schiff base ligand, N,N'-bis-(2-thiophenecarboxaldimine)-3,3'
      diaminobenzidine (L) obtained from condensation of 2-thiophenecarboxaldehyde and
      3,3'-diaminobenzidine, was used to synthesize the complexes of type, [M2L2]Cl4
      [M=Co(II), Ni(II), Cu(II), Cd(II) and Hg(II)]. The newly synthesized ligand (L)
      was characterized on the basis of the results of elemental analysis, FT-IR, 1H
      NMR, 13C NMR, mass spectroscopic studies and single crystal X-ray
      crystallography. The characteristic resonance signals in 1H NMR and 13C NMR
      spectra indicated the presence of azomethine group as a result of condensation
      reaction. The stoichiometry, bonding and stereochemistries of complexes were
      ascertained on the basis of results of elemental analysis, magnetic
      susceptibility measurements, molar conductance and spectroscopic studies viz., FT
      IR, 1H and 13C NMR, UV-vis and EPR. EPR, UV-vis and magnetic moment data revealed
      an octahedral geometry for complexes with distortion in Cu(II) complex and
      conductivity data show 1:2 electrolytic nature of complexes. Absoption and
      fluorescence spectroscopic studies supported that Schiff base ligand L and its
      Co(II), Ni(II) and Cu(II) complexes exhibited significant binding to calf thymus
      DNA. The complexes exhibited higher affinity to calf thymus DNA than the free
      Schiff base ligand L.

PMID- 21715222
TI  - Kinetics of catalyzed hydrolysis of 4-methylumbelliferyl caprylate (MUCAP)
      salmonella reagent.
AB  - The kinetics of chemical hydrolysis including neutral, acid- and base-catalyzed
      hydrolysis of 4-methylumbelliferyl caprylate (MUCAP) salmonella reagent were
      studied at different temperatures. The rate constants and activation parameters
      were determined by following the build-up of fluorescence peak of the hydrolysis
      product 4-methylumbelliferone (4-MU). The time scale of esterase enzyme
      hydrolysis caused by salmonella was compared with chemical hydrolysis as a
      background process.

PMID- 21715223
TI  - Flavonoid-DNA binding studies and thermodynamic parameters.
AB  - Interactional studies of new flavonoid derivatives (Fl) with chicken blood ds.DNA
      were investigated spectrophotometrically in DMSO-H2O (9:1 v/v) at various
      temperatures. Spectral parameters suggest considerable binding between the
      flavonoid derivatives studied and ds.DNA. The binding constant values lie in the
      enhanced-binding range. Thermodynamic parameters obtained from UV studies also
      point to strong spontaneous binding of Fl with ds.DNA. Viscometric studies
      complimented the UV results where a small linear increase in relative viscosity
      of the DNA solution was observed with added optimal flavonoid concentration. An
      overall mixed mode of interaction (intercalative plus groove binding) is proposed
      between DNA and flavonoids. Conclusively, investigated flavonoid derivatives are
      found to be strong DNA binders and seem to be promising drug candidates like
      their natural analogues.

PMID- 21715224
TI  - A comparison of clinical features of Japanese encephalitis virus infection in the
      adult and pediatric age group with Acute Encephalitis Syndrome.
AB  - BACKGROUND: Japanese encephalitis (JE) has traditionally been regarded as a
      disease of children. The age shift in JE patients in Assam, India in last few
      years has become a cause of concern. Comparison on clinical features of adult and
      pediatric JE patients has not been evaluated. OBJECTIVE: To compare clinical
      features of adult and pediatric with JE virus infection. STUDY DESIGN: From
      January 2008 to January 2010, 550 hospitalized patients with Acute Encephalitis
      Syndrome were enrolled. 259 (47.1%) were serologically confirmed as JE of which
      66.4% were adult and 33.6% were pediatric. Data extracted from these patients
      were analyzed. RESULTS: Fever was the most common symptom in both the adult and
      pediatric. When compared with adult, significantly higher percentage of pediatric
      had neck rigidity, convulsions, abnormal behavior, seizures and elevated
      aspartate transaminase (P<0.05). Serum bilirubin levels were higher in 2.3% of
      adult but normal in all the pediatric. We found significantly higher mean
      elevated level of protein and WBC in CSF in adult (P<0.001) and mean elevated
      aspartate transaminase level (P<0.001) in pediatrics. There was no difference in
      mortality rate between pediatric and adult (8.2% vs. 4.4%, P=0.647). CONCLUSIONS:
      This study provides some significant differences in clinical features of
      pediatric and adult with JE. Age shift may be due to the invasion of the disease
      into new demography or some change in the virus strain over time. The Government
      of India has initiated an adult JE vaccination programme for the first time in
      Assam in 2011.

PMID- 21715225
TI  - Conflict and inhibition in the cued-Go/NoGo task.
AB  - OBJECTIVE: Current debate centres on the inhibitory and conflict interpretations
      of the N2 and P3 components of the event-related potential (ERP). We examined
      behavioural responses and ERPs in a cued-Go/NoGo task. METHODS: Participants were
      required to inhibit a planned response (NoGo target after Go cue), change a
      planned response to a different one (Invalid cueing), and activate an unexpected
      response (Go target after NoGo cue). RESULTS: Responses were slower when
      participants had to change a planned response, and execute an unplanned response.
      N2 was more negative whenever the presented target required a different response
      to what was expected based on the cue. In contrast, P3 was increased when
      participants had to change or inhibit a planned response, but not when executing
      a response where none was planned. CONCLUSIONS: N2 results lend support to the
      conflict account, while P3 reflects cancellation of a planned response.
      SIGNIFICANCE: This paper provides the first test of conflict involving activation
      of an unplanned response in a cued-Go/NoGo task.

PMID- 21715226
TI  - Region and frequency specific changes of spectral power in Alzheimer's disease
      and mild cognitive impairment.
AB  - OBJECTIVES: To find out whether healthy control (HC), amnestic mild cognitive
      impairment (aMCI), and Alzheimer's disease (AD) subjects exhibit region and
      frequency specific spectral power differences and whether the spectral power
      changes correlate with domain-specific cognitive function. METHODS: Forty-one AD,
      38 aMCI, and 39 HC subjects underwent quantitative EEG and comprehensive
      neuropsychological tests. Repeated measures analysis of variance was performed to
      identify differences in EEG spectral power among the three groups by scalp region
      and EEG frequency. Correlations between region and frequency specific spectral
      powers and neuropsychological test scores were evaluated. RESULTS: Temporal and
      parieto-occipital theta band powers were highest in AD. Whereas, parieto
      occipital alpha and frontal and temporal beta 2 band powers were highest in HC
      and lowest in AD (p<0.05). Temporal and parieto-occipital theta powers negatively
      correlated with verbal and visuospatial memory recall, while parieto-occipital
      alpha and temporal beta 2 powers positively correlated with verbal memory recall
      (p<0.01). CONCLUSIONS: Region and frequency specific oscillatory characteristics
      of EEG reflect domain-specific cognitive function in patients with aMCI and AD.
      SIGNIFICANCE: Region and frequency specific spectral powers have clinical
      implications as additional markers differentiating AD, aMCI, and HC.

PMID- 21715227
TI  - Cloning and characterization of beta-agarase AgaYT from Flammeovirga yaeyamensis
      strain YT.
AB  - A bacterium with potent agar-degrading capability was isolated from the surface
      of a red algae, Gracilaria tenuistipitata. Based on phenotypic characteristics,
      16S rDNA gene sequence and a phylogenetic analysis, this bacterium was identified
      and named as Flammeovirga yaeyamensis strain YT. PCR using homology-based
      degenerate primers was employed to clone any agarase gene belonging to GH16
      family encoded in F. yaeyamensis strain YT. The resolved 1512 nucleotides
      revealed that the cloned gene, namely AgaYT, encodes a protein of 503 amino acids
      comprising a signal peptide, a glycosyl hydrolase catalytic module and a C
      terminal domain with an unknown function. The recombinant protein r-AgaYT is an
      endo-type beta-agarase hydrolyzing agarose to yield neoagarobiose and
      neoagarotetraose as the main hydrolytic products. The specific activity of r
      AgaYT was determined about 178.6 U mg(-1) at 40 degrees C and pH 8.0.

PMID- 21715228
TI  - Integrative taxonomy of the Pavlovophyceae (Haptophyta): a reassessment.
AB  - The Pavlovophyceae (Haptophyta) contains four genera (Pavlova, Diacronema,
      Exanthemachrysis and Rebecca) and only thirteen characterised species, several of
      which are important in ecological and economic contexts. We have constructed
      molecular phylogenies inferred from sequencing of ribosomal gene markers with
      comprehensive coverage of the described diversity, using type strains when
      available, together with additional cultured strains. The morphology and
      ultrastructure of 12 of the described species was also re-examined and the
      pigment signatures of many culture strains were determined. The molecular
      analysis revealed that sequences of all described species differed, although
      those of Pavlova gyrans and P. pinguis were nearly identical, these potentially
      forming a single cryptic species complex. Four well-delineated genetic clades
      were identified, one of which included species of both Pavlova and Diacronema.
      Unique combinations of morphological/ultrastructural characters were identified
      for each of these clades. The ancestral pigment signature of the Pavlovophyceae
      consisted of a basic set of pigments plus MV chl cPAV, the latter being entirely
      absent in the Pavlova + Diacronema clade and supplemented by DV chl cPAV in part
      of the Exanthemachrysis clade. Based on this combination of characters, we
      propose a taxonomic revision of the class, with transfer of several Pavlova
      species to an emended Diacronema genus. The evolution of the class is discussed
      in the context of the phylogenetic reconstruction presented.

PMID- 21715229
TI  - Advances in transfusion medicine in the first decade of the 21st century:
      Advances in miniaturized technologies.
AB  - Several miniaturized high throughput technologies have been developed in the last
      decade, primarily to study genomic structures and gene expression patterns under
      various conditions. At the same time, the microarrays, biosensors, integrated
      microfluidic lab-on-a-chip devices, next generation sequencing or digital PCR are
      gradually finding their diagnostic applications, although their suitability for
      specialised diagnostic fields has still to be assessed. In this review we discuss
      the potential applications of the new technologies to blood testing.

PMID- 21715230
TI  - The role of sleep in forgetting in temporal lobe epilepsy: a pilot study.
AB  - The purpose of this study was to examine how sleep impacts memory function in
      temporal lobe epilepsy (TLE). Patients with TLE (n=7) and control subjects (n=9)
      underwent training and overnight testing on (1) a motor sequence task known to
      undergo sleep-dependent enhancement in healthy subjects, and (2) the selective
      reminding test, a verbal memory task on which patients with TLE have shown
      impaired performance 24 hours after training. Sleep data were collected by
      polysomnography. Results indicate that patients with TLE display greater
      forgetting on the selective reminding test compared with controls over 12 hours
      of daytime wakefulness, but not over a similar period including a night of sleep.
      Slow wave sleep is correlated with overnight performance change on the selective
      reminding test. Patients with TLE show no deficit in sleep-dependent motor
      sequence task improvement. The findings provide potential insight into the
      pattern and pathophysiology of forgetting in TLE.

PMID- 21715231
TI  - Conservation of the axilla: an audit of sentinel lymph node biopsy after a new
      start.
AB  - BACKGROUND: Four hundred twenty-eight patients with a diagnosis of breast cancer
      were assessed. All patients underwent axillary ultrasonographic scanning
      preoperatively or at the time of initial breast imaging. Suspicious axillary
      glands underwent core needle biopsy under ultrasonographic guidance. PATIENTS AND
      METHODS: The majority of patients were in the age range of 40 to 80 years.
      Sentinel lymph node biopsy (SLNB) was performed in 360 patients. RESULTS: Sixty
      eight patients had axillary clearance as a first axillary procedure. Of these
      patients, 55 had a preoperative diagnosis of a positive axillary gland in the
      axilla on ultrasonographically guided core needle biopsy, and 13 had clinically
      palpable axillary lymph glands. Seventy-one patients (21%) had a positive
      sentinel lymph node on histopathologic examination after hematoxylin and eosin (H
      & E) staining. Preoperative scans of the axilla had been reported as normal in
      these patients. In 68 patients, further axillary surgery was performed to clear
      the axilla; 24 of these patients (35%) had more positive glands in the axilla. In
      44 patients (65%) the sentinel lymph glands were the only positive glands. Of 224
      patients with a tumor size <= 20 mm, there were 30 patients (14%) who had a
      positive sentinel node. Of 136 patients with a tumor size > 20 mm, there were 41
      patients (33%) with positive sentinel nodes. CONCLUSIONS: Sentinel lymph node
      biopsy in breast cancer allowed conservation of the axilla in 80% (289/360) of
      patients with negative sentinel lymph nodes in this study. Preoperative
      ultrasonographically guided core needle biopsy reduced the need for a second
      operation in 55 patients (13%).

PMID- 21715232
TI  - Five-year follow-up of transcatheter intracardiac echocardiography-assisted
      closure of interatrial shunts.
AB  - OBJECTIVE: We sought to prospectively evaluate long-term follow-up results of
      intracardiac echocardiography-aided transcatheter closure of interatrial shunts
      in adults. BACKGROUND: Intracardiac echocardiography improves the safety and
      effectiveness of transcatheter device-based closure of interatrial shunts, but
      its impact on long-term follow-up is unknown. METHODS: Over a 5-year period, we
      prospectively enrolled 258 consecutive patients (mean age 48 +/- 19.1 years, 169
      females) who had been referred to our centre for catheter-based closure of
      interatrial shunts. All patients were screened with transesophageal
      echocardiography before the operation. Eligible patients underwent intracardiac
      echocardiography study and attempted closure. RESULTS: After intracardiac
      echocardiography study and measurements, 18 patients did not proceed to
      transcatheter closure due to unsuitable rims, atrial myxoma not diagnosed by
      preoperative transesophageal echocardiography or inaccurate transesophageal
      echocardiography measurement of defects more than 40 mm. The remaining 240
      patients underwent transcatheter closure: transesophageal echocardiography
      planned device type and size were modified in 108 patients (45%). Rates of
      procedural success, predischarge occlusion and complication were 100%, 94.2% and
      5%, respectively. On mean follow-up of 65 +/- 15.3 months, the follow-up
      occlusion rate was 96.5%. There were no cases of aortic/atrial erosion, device
      thrombosis or atrioventricular valve inferences. CONCLUSIONS: Intracardiac
      echocardiography-guided interatrial shunt transcatheter closure is safe and
      effective and appears to have excellent long-term results, potentially minimizing
      the complications resulting from incorrect device selection and sizing.

PMID- 21715233
TI  - Direct electron transfer enhancement of covalently bound tyrosinase to glassy
      carbon via Woodward's reagent K.
AB  - This work describes the reaction mechanism for chemical modification of
      tyrosinase by Woodward's Reagent K and its covalent attachment to a glassy carbon
      electrode. The spectrophotometric studies revealed that the modification does not
      cause a significant structural change to tyrosinase. The direct electrochemistry
      of modified enzyme was achieved after immobilization on an oxidatively activated
      glassy carbon electrode. The enzyme film exhibited a pair of well-defined quasi
      revesible voltammetric peaks corresponding to the Cu (II)/Cu (I) redox couple
      located in the active site of tyrosinase. The formal potential of immobilized
      enzyme was measured to be 90mV (vs. Ag/AgCl) in phosphate buffer solution at pH
      7.0. The charge-transfer coefficient and apparent heterogeneous electron transfer
      rate constant were estimated to be 0.5 and 0.9+/-0.06s(-1), respectively.
      Finally, the electrochemical behavior of the immobilized enzyme in the presence
      of caffeic acid and L-3,4-dihydroxyphenylalanine as substrates was investigated.
      The amperometric study of biosensor toward L-3,4-dihydroxyphenylalanine resulted
      a linear response in the concentration range from 1.66*10(-6) to 8.5*10(-5)M with
      detection limit of 9.0*10(-5)M and sensitivity of 135mAMUM(-1)cm(-2).

PMID- 21715234
TI  - [Treatment of iron deficiency by a bolus intravenous iron dextran in peritoneal
      dialysis].
AB  - INTRODUCTION: The main objective of this study is to determine whether a single
      dose of iron dextran can correct iron deficiency during a period of four months
      in peritoneal dialysis patients. METHOD: This was a prospective observational
      study in peritoneal dialysis patients who had anemia (hemoglobin<11g/dL) and iron
      deficiency (ferritin<100MUg/L and/or transferrin saturation<20%). Patients who
      were resistant to oral iron or who could not tolerate oral iron were included in
      the study. At baseline, based on the iron deficiency estimation, a single dose of
      iron dextran was infused over four hours. RESULTS: Of 17 patients included, 12
      completed the study. The mean iron dose infused was 742+/-150mg. No clinically
      significant adverse event was reported during the infusion. Four months after the
      iron dextran infusion there was a significant increase of the mean hemoglobin
      level (10.1+/-0.7g/dl vs 11.4+/-1.2g/dL, P<0.05), the mean blood ferritin level
      (66+/-46mg/L vs 212+/-121mg/L, P<0.05) and the mean transferrin saturation (14+/
      5% vs 23+/-8, P<0.05). Four months after the iron infusion 10 patients had a
      blood ferritin level higher than 100MUg/L and a transferrin saturation higher
      than 20%. There was no significant modification of the erythropoietin dose during
      the four months period. CONCLUSION: In patients treated by peritoneal dialysis,
      the anemia due to iron deficiency can be treated by a single infusion of iron
      dextran for a period of four months.

PMID- 21715235
TI  - Haematoma of pectineus muscle after total hip arthroplasty.
AB  - The complications of total hip arthroplasty (THA) during the immediate
      postoperative period consist mainly in dislocation of the prosthesis, haematomas
      under antocoagulants, early infections, dismantling of osteotomy, neurological
      injury, heterotopic ossification and delayed restoration of the range of motion
      of the hip joint. We present here an infrequently described case of haematoma of
      the pectineus muscle following THA. Haematomas are not described in literature
      except in rare cases of compressive haematoma associated with neurological
      injury. In our case, the intraoperative blood losses were not particularly
      massive, there were no anticoagulation accident or postoperative trauma and no
      secondary deglobulinization. The question to be considered is that of a possible
      stretching of the pectineus during hip dislocation, and possibly during the
      surgical procedures for the implementation of the prosthesis with increased
      length, as it is the case here. Haematomas of the pectineus are probably
      underdiagnosed as they imitate other, more known, symptomatologies.

PMID- 21715236
TI  - Management of esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma is increasing in Western countries
      with a tendency to exceed that of squamous-cell carcinoma. Prognosis is
      unfavorable with 5-year survival less than 15%, irrespective of treatment and the
      stage. At the time of diagnosis, more than two thirds of patients have a non
      operable cancer because of extension or associated co-morbidities. Most studies
      have included different tumoral locations (esophagus and stomach) and different
      histological types (adenocarcinoma and squamous-cell carcinoma), making it
      difficult to interpret results. Surgery is currently the standard treatment for
      small tumors. Surgery should be preceded by neo-adjuvant treatment for patients
      with locally advanced resectable tumors, either preoperative chemotherapy or
      preoperative chemoradiation therapy. The therapeutic choice should be decided
      during multidisciplinary meetings according to patient and tumor characteristics
      and the expertise of the center. For patients with contraindications to surgery,
      exclusive chemoradiation therapy is recommended. Herein we reviewed and
      synthesized the different therapeutic strategies for esophageal adenocarcinoma.

PMID- 21715237
TI  - Epiploic appendagitis.

PMID- 21715238
TI  - Duodenal diverticulum associated with annular pancreas: a rare cause of severe
      cholangitis.
AB  - Duodenal diverticulum is a common occurrence but most are asymptomatic. However,
      in some cases, they can cause mechanical biliary compression. We report the case
      of a duodenal diverticulum in a 64-year-old woman revealed by severe cholangitis
      with septic shock and a liver abscess. Associated annular pancreas was found. We
      discuss the various investigations to diagnose these two entities as well as the
      therapeutic strategy in this unique combination of disease.

PMID- 21715239
TI  - The effect of balance confidence and context on functional reach ability in
      healthy older adults.
AB  - OBJECTIVE: To assess functional reach (FR) ability in 4 contexts in older adults
      (>= 60 years) with high balance confidence (HBC) and low balance confidence
      (LBC). DESIGN: A repeated-measures design was used to compare 2 groups in 4
      reaching contexts. SETTING: Community setting. SUBJECTS: Twenty-four healthy
      older adults with HBC and 27 healthy older adults with LBC. METHODS: FR distance
      was assessed in 4 contexts presented in random order: (1) traditional FR (TFR);
      (2) functional reach on foam (FRF); (3) object present functional reach (OPFR);
      and (4) object present functional reach on foam (OPFRF). For TFR and FRF, 3
      trials were performed for each task, and the average reach distance across 3
      trials was calculated. During the OPFR and OPFRF contexts, the object was moved
      toward or away from the participant in 1.3-cm increments until maximal reach
      distance to the object was obtained. MAIN OUTCOME MEASURE: Maximal reach distance
      in each of the 4 FR contexts. RESULTS: Participants in the HBC group scored
      significantly higher than did participants in the LBC group regardless of
      reaching contexts (P =.004). For both balance confidence groups, reaching
      distance increased significantly from FRF to TFR to OPFRF to OPFR (P < .001).
      CONCLUSION: The results of this study highlight the beneficial effect of an
      external target on balance performance, even with the added challenge of an
      unstable surface. These findings suggest that although balance performance is
      greater for persons with HBC, the same pattern of reaching ability in differing
      FR contexts is found regardless of whether balance confidence is high or low. The
      clinical utility of these findings pertain to the importance of the use of task
      objects during FR balance assessment to determine an individual's balance
      capacity. Future research is needed to assess the effectiveness of context
      oriented reaching tasks in balance training programs.

PMID- 21715240
TI  - Folic acid supplementation improves vascular function in professional dancers
      with endothelial dysfunction.
AB  - OBJECTIVE: To determine if folic acid supplementation improves vascular function
      (brachial artery flow-mediated dilation [FMD]) in professional dancers with known
      endothelial dysfunction. DESIGN: Prospective cross-sectional study. SETTING:
      Academic institution in the Midwestern United States. SUBJECTS: Twenty-two
      professional ballet dancers volunteered for this study. MAIN OUTCOME MEASURES:
      Subjects completed a 3-day food record to determine caloric and micronutrient
      intake. Menstrual status was determined by interview and questionnaire.
      Endothelial function was determined as flow-induced vasodilation measured by high
      frequency ultrasound of the brachial artery. A change in brachial diameter of <5%
      to hyperemic flow stimulus was defined a priori as endothelial dysfunction.
      Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD
      testing was then repeated. Serum whole blood was measured for folic acid levels
      before and after supplementation. RESULTS: Sixty-four percent of dancers (n = 14)
      had abnormal brachial artery FMD (<5%) (mean +/- standard deviation, 2.9% +/-
      1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in
      all the subjects (7.1% +/- 2.3%; P < .0001). CONCLUSIONS: This study reveals that
      vascular endothelial function improves in dancers after supplementation with
      folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically
      important implications for future cardiovascular disease risk prevention.

PMID- 21715241
TI  - Associations between polybrominated diphenyl ether (PBDE) flame retardants,
      phenolic metabolites, and thyroid hormones during pregnancy.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are chemical additives used as
      flame retardants in commercial products. PBDEs are bioaccumulative and persistent
      and have been linked to several adverse health outcomes. OBJECTIVES: This study
      leverages an ongoing pregnancy cohort to measure PBDEs and PBDE metabolites in
      serum collected from an understudied population of pregnant women late in their
      third trimester. A secondary objective was to determine whether the PBDEs or
      their metabolites were associated with maternal thyroid hormones. METHODS: One
      hundred forty pregnant women > 34 weeks into their pregnancy were recruited into
      this study between 2008 and 2010. Blood samples were collected during a routine
      prenatal clinic visit. Serum was analyzed for a suite of PBDEs, three phenolic
      metabolites (i.e., containing an -OH moiety), and five thyroid hormones. RESULTS:
      PBDEs were detected in all samples and ranged from 3.6 to 694 ng/g lipid. Two
      hydroxylated BDE congeners (4'-OH-BDE 49 and 6-OH-BDE 47) were detected in > 67%
      of the samples. BDEs 47, 99, and 100 were significantly and positively associated
      with free and total thyroxine (T4) levels and with total triiodothyronine levels
      above the normal range. Associations between T4 and PBDEs remained after
      controlling for smoking status, maternal age, race, gestational age, and parity.
      CONCLUSIONS: PBDEs and OH-BDEs are prevalent in this cohort, and levels are
      similar to those in the general population. Given their long half-lives, PBDEs
      may be affecting thyroid regulation throughout pregnancy. Further research is
      warranted to determine mechanisms through which PBDEs affect thyroid hormone
      levels in developing fetuses and newborn babies.

PMID- 21715242
TI  - Prenatal lead exposure and weight of 0- to 5-year-old children in Mexico city.
AB  - BACKGROUND: Cumulative prenatal lead exposure, as measured by maternal bone lead
      burden, has been associated with smaller weight of offspring at birth and 1 month
      of age, but no study has examined whether this effect persists into early
      childhood. OBJECTIVE: We investigated the association of perinatal maternal bone
      lead, a biomarker of cumulative prenatal lead exposure, with children's attained
      weight over time from birth to 5 years of age. METHODS: Children were weighed at
      birth and at several intervals up until 60 months. Maternal tibia and patella
      lead were measured at 1 month postpartum using in vivo K-shell X-ray
      fluorescence. We used varying coefficient models with random effects to assess
      the association of maternal bone lead with weight trajectories of 522 boys and
      477 girls born between 1994 and 2005 in Mexico City. RESULTS: After controlling
      for breast-feeding duration, maternal anthropometry, and sociodemographic
      characteristics, a 1-SD increase in maternal patella lead (micrograms per gram)
      was associated with a 130.9-g decrease in weight [95% confidence interval (CI), 
      227.4 to -34.4 g] among females and a 13.0-g nonsignificant increase in weight
      among males (95% CI, -73.7 to 99.9 g) at 5 years of age. These associations were
      similar after controlling for concurrent blood lead levels between birth and 5
      years. CONCLUSIONS: Maternal bone lead was associated with lower weight over time
      among female but not male children up to 5 years of age. Given that the
      association was evident for patellar but not tibial lead levels, and was limited
      to females, results need to be confirmed in other studies.

PMID- 21715243
TI  - Exposure to PBDEs in the office environment: evaluating the relationships between
      dust, handwipes, and serum.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame
      retardants in consumer products and are ubiquitous in residential indoor air and
      dust. However, little is known about exposure in the office environment.
      OBJECTIVES: We examined relationships between PBDE concentrations in the office
      environment and internal exposure using concurrent measurements of PBDEs in
      serum, handwipes, and office dust. METHODS: We collected serum, dust, and
      handwipe samples from 31 participants who spent at least 20 hr/week in an office.
      We used a questionnaire to collect information about work and personal habits.
      RESULTS: We found positive associations between PBDEs in room dust, handwipes (a
      measure of personal exposure), and serum. PBDE office dust concentrations were
      weakly correlated with measurements in handwipes: r = 0.35 (p = 0.06) for
      pentaBDE (sum of BDE congeners 28/33, 47, 99, 100, and 153) and 0.33 (p = 0.07)
      for BDE-209. Hand washing also predicted pentaBDE levels in handwipes: low hand
      washers had 3.3 times the pentaBDE levels in their handwipes than did high hand
      washers (p = 0.02). PentaBDE in handwipes predicted pentaBDE levels in serum (p =
      0.03): Serum concentrations in the highest handwipe tertile were on average 3.5
      times the lowest handwipe tertile. The geometric mean concentration of pentaBDEs
      in serum was 27 ng/g lipid. We detected BDE-209 in 20% of serum samples, at
      levels ranging from < 4.8 to 9.7 ng/g lipid. CONCLUSION: Our research suggests
      that exposure to pentaBDE in the office environment contributes to pentaBDE body
      burden, with exposure likely linked to PBDE residues on hands. In addition, hand
      washing may decrease exposure to PBDEs.

PMID- 21715244
TI  - Abnormal histone modifications in PBMCs from patients with psoriasis vulgaris.
AB  - Excessive keratinocyte proliferation is thought to be responsible for the
      formation and development of psoriasis vulgaris. Evidence indicates that
      epigenetic modifications are associated with aberrant gene expression, however,
      nothing is known about the status of histone modifications in psoriasis vulgaris.
      We investigated alterations in histone modifications in patients with psoriasis
      vulgaris. Global histone H3/H4 acetylation and H3K4/H3K27 methylation in
      peripheral blood mononuclear cells from 30 psoriatic patients and 20 healthy
      control subjects were quantified by the EpiQuik(TM) global histone H3/H4
      acetylation and H3K4/H3K27 methylation assay kit. The mRNA levels of 12 members
      of 3 classes of chromatin modifier genes were measured by real-time quantitative
      polymerase chain reaction. Compared with normal controls, global histone H4
      hypoacetylation was observed in PBMCs from psoriasis vulgaris patients. There was
      a negative correlation between the degree of histone H4 acetylation and disease
      activity in patients as measured by PASI. Global levels of H3 acetylation,
      H3K4/H3K27 methylation did not significantly differ between psoriatic patients
      and controls. mRNA levels of P300, CBP and SIRT1 were significantly reduced in
      PBMCs from patients with psoriasis vulgaris compared with healthy controls, while
      mRNA expression levels of HDAC1, SUV39H1 and EZH2 was significantly increased in
      psoriatic patients.We conclude that histone modifications are aberrant in the
      PBMCs of psoriasis vulgaris patients.

PMID- 21715245
TI  - Eosinophilic panniculitis in the areas of previous allergen immunotherapy: a
      "recall panniculitis"?

PMID- 21715248
TI  - Residents'corner May 2011.

PMID- 21715249
TI  - Psoriatic arthritis: from a dermatological perspective.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with
      psoriasis, and included among the seronegative spondyloarthropathies. The
      presence of cutaneous psoriasis is very important for correct and early diagnosis
      of PsA, because the cutaneous lesions precede the appearance of joint
      manifestations. Thus, dermatologists are in a position to detect the condition at
      its inception. PsA is clinically subdivided into asymmetric oligoarticular
      arthritis, symmetric polyarthritis, distal interphalanges predominant, arthritis
      mutilans, and spondylitis types. PsA has several unique characteristics, such as
      enthesopathy, dactylitis and abnormal bone remodeling. Genetic, environmental,
      and immunological factors are important in its development. The triggering role
      of physical stress is seen in the "deep Koebner" phenomenon, which causes
      inflammation in the synovial membrane and in enthesis, resulting in peripheral
      arthritis. Cellular infiltrates such as activated T-cells and macrophages are
      thought to play important roles in the induction of inflammatory and destructive
      processes in joint tissues, as well as psoriatic skin. New ideas regarding the
      involvement of the IL-23/Th17 axis have emerged, and the dramatic effects of
      targeting therapies have highlighted the physiological role of key cytokines in
      psoriasis. Current views on the pathogenesis of PsA are reviewed from a
      dermatological perspective.

PMID- 21715250
TI  - Urticariform striae distensae with severe pruritus and pain in an obese woman.

PMID- 21715251
TI  - A novel mutation within the 2B rod domain of keratin 9 in a Chinese pedigree with
      epidermolytic palmoplantar keratoderma combined with knuckle pads and
      camptodactyly.
AB  - Knuckle pads and camptodactyly are overlapping symptoms associated with many
      genetic and environmental factors. To the best of our knowledge, all reported
      cases of epidermolytic palmoplantar keratoderma (EPPK) with knuckle pads have
      been without accompanying camptodactyly. We here report a novel KRT9 mutation
      EPPK family with combined knuckle pads and camptodactyly. All the EPPK-affected
      individuals in this southern Chinese pedigree suffered severe diffuse palmar and
      plantar hyperkeratosis including hyperhidrosis and cuticle splitting: 3 females
      presented EPPK only, 8 adult males had notably severe knuckle pads and
      camptodactyly as well as EPPK, and one 6-year-old boy manifested EPPK with
      knuckle pads. Haplotype analysis excluded the known candidate loci for
      camptodactyly and/or knuckle pad-like phenotypes on chromosomes 13q12, 3q11.2
      q13.12, 1q24-q25, 4p16.3 and 16q11.1-q22, while only the markers D17S1787 and
      D17S579 flanking KRT9 showed co-segregation with EPPK. Then a novel c.T1373C
      (p.L458P) mutation within the sixth exon of KRT9 was validated, and this mutation
      presented a more severe pathogenicity than the previously reported p.L458F. We
      speculated that KRT9 plays a complicated role in the genesis of EPPK with knuckle
      pads and camptodactyly, which needs to be further investigated.

PMID- 21715252
TI  - Hypohidrotic ectodermal dysplasia caused by a missense mutation in the EDA gene.

PMID- 21715253
TI  - [Targeting the RAS signalling pathway in cancer].
AB  - RAS proteins are among the first proteins to demonstrate a crucial implication in
      the cell cycle regulation. The RAS signalling pathway plays a key role in the
      regulation of cell cycle through the activation of numerous downstream pathways
      including the RAF/MEK/ERK, PI3K/AKT/mTOR, RAL and PKC pathways. These pathways
      are involved in gene transcription, regulation of cell survival and angiogenesis.
      As the RAS signalling pathway was shown to be altered in several cancers,
      molecularly targeted agents that trigger various components of this pathway have
      been evaluated in clinical practice. This paper first reviews the regulation
      processes of the RAS protein in cancer, as well as RAS downstream main signalling
      pathways. Therapeutic approaches to target RAS or some of its effectors are then
      detailed. Finally, the ability of RAS mutations to predict response to EGFR
      targeting agents is discussed in the context of colorectal and lung cancers.

PMID- 21715254
TI  - [Blood supply and demand at the Fifth District Health Centre in Bamako (Mali)].
AB  - BACKGROUND: An adequate uncontaminated blood supply is an essential element of an
      effective health care system. A regional blood transfusion policy was defined in
      2004 by the Direction of Health in Bamako, Mali. The objective of this study is
      to analyse the coverage of transfusion needs at the Fifth District health Center
      in Bamako after the implementation of this policy. METHOD: This prospective
      study, conducted from December 2006 through May 2007, included 134 patients for
      whom transfusion orders were recorded in the laboratory. The coverage rate of
      transfusion needs was estimated by dividing the number of units transfused by the
      number of units that health professionals requested. RESULTS: The blood supply
      was regular (46 units per month, on average) and consistent with demand (59 units
      per month on average). Overall, 75% of the transfusions were required for
      obstetric complications. All patients received at least one 450-mL unit of whole
      blood. The coverage of transfusion needs has reached 65% of the total number of
      units required (95% CI = 60-70%). CONCLUSION: The implementation of a functioning
      system of blood transfusion is complex. In Bamako, a system based on a
      centralized transfusion center met a high proportion of the needs in a reference
      hospital where demand was high while ensuring a high level of patient safety.
      Further studies are needed to guide the implementation of feasible and
      sustainable strategies for providing sufficient quantities of safe blood in other
      contexts and to assess the impact of these different strategies on global health,
      and on maternal health in particular.

PMID- 21715255
TI  - Cytotoxic effects of commercial wheatgrass and fiber towards human acute
      promyelocytic leukemia cells (HL60).
AB  - Cytotoxicity, the possible selective activity upon HL60 as well as the anti
      proliferation effect of local health supplement wheatgrass and mixture of fibers
      were investigated in vitro using various cancerous cell line and normal blood
      cell culture. The IC(50) of wheatgrass-treated HL60 (17.5 +/- 1.1, 12.5 +/- 0.3,
      and 16 +/- 0.5 microgram/ml for 24, 48 and 72 h, respectively) and fibers-treated
      HL60 (86.0 +/- 5.5, 35.0 +/- 2.5, and 52.5 +/- 4.5 microgram/ml for 24, 48 and 72
      h, respectively) showed that both extracts possessed optimum effect after 48
      hours of treatment. No significant cytotoxic effect was observed on other type of
      cells. For trypan blue dye exclusion method, wheatgrass reduced the number of
      viable cells by 13.5% (+/-1.5), 47.1% (+/-3.6), and 64.9% (+/-2.7) after 24, 48
      and 72 h exposure, respectively. Mixture of fibers reduced the number of viable
      cells by 36.4% (+/-2.3), 57.1% (+/-3.1), and 89.0% (+/-3.4) after 24, 48 and 72 h
      exposure, respectively, indicated that necrosis is also an alternative to the
      apoptotic mechanism of cell death. Annexin-V/propidium iodide staining revealed
      that both extracts induced apoptosis where early apoptosis had been detected
      concurrently with the reduction of percentage of cell viability. Cell cycle
      analysis revealed that in HL60, the percentage of apoptosis increased with time
      (wheatgrass: 16.0% +/- 2.4, 45.3% +/- 3.4 and 39.6% +/- 4.1; mixture of fibers:
      14.6% +/- 1.8, 45.4% +/- 2.3 and 45.9% +/- 1.2) after exposure for 24, 48 and 72
      h, respectively at the concentration of 100 microgram/ml and showed optimum
      effect at 48 hours. Thus, these health products can be a potential alternative
      supplement for leukaemia patients.

PMID- 21715256
TI  - Hypophagic and hypolocomotive effects of metachloro phenyl piperazine in rats
      treated with theophylline and caffeine.
AB  - Long term intake of coffee is known to produce anxiety and suppression of
      appetite. 5- hydroxytryptamine (5-HT) acting via 5-HT-2C receptors elicits
      anorexia and anxiety. The present study is design to monitor metachloro phenyl
      piperazine (m-CPP) at a dose of 3mg/ml/kg, induces hypophagia and hypolocomotion
      in rats taking a solution of caffeine (a component of coffee and tea) or
      theophylline (a component of tea) as a sole source of water. We found that
      hypophagic and hypolocomotive effects of m-CPP were attenuated in theophylline
      but not in caffeine treated animals suggesting that long term intake of
      theophylline may attenuate anorexiogenic and anxiogenic effects of 5-HT. A
      possible role of 5-HT-2C receptors in the modulation of anxiety and appetite in
      people drinking coffee or tea discussed.

PMID- 21715257
TI  - Formulation and in vitro evaluation of ofloxacin-ethocel controlled release
      matrix tablets prepared by wet granulation method: influence of co-excipients on
      drug release rates.
AB  - Being controlled release dosage forms, tablets allow an improved absorption and
      release profiles of Ofloxacin. The fact that drugs with fine particles size can
      be compressed well after wetting, so in our research studies Ofloxacin controlled
      release matrix tablets were prepared by wet granulation technique. In order to
      investigate the potential of Ethyl cellulose ether derivatives as a matrix
      material, Ofloxacin formulations with different types and grades of Ethocel were
      prepared at several drug-to-polymer ratios. The method adopted for in vitro drug
      release studies was USP Method-1 (rotating Basket Method) by Pharma test
      dissolution apparatus using phosphate buffer 7.4 pH as a dissolution medium.
      Various Kinetic models were employed to the formulations for the purpose of
      determination of release mechanism. A comparative study was performed between the
      tested Ofloxacin-Ethocel formulations and a standard reference obtained from the
      local market. F1 dissimilarity factor and f2 similarity factor were applied to
      the formulations for the checking of dissimilarities and similarities between the
      tested formulations and reference standard.

PMID- 21715258
TI  - Neuroprotective effect of vitamin C against PTZ induced apoptotic
      neurodegeneration in adult rat brain.
AB  - The present study was designed to observe the effect of PTZ on expression of
      caspsae-3, and to evaluate the neuroprotective role of vitamin C (vit-C) against
      PTZ-induced apoptotic neurodegeneration in adult rat brain. We observed that
      administration of a single conclusive dose of pentylenetetrazol (PTZ 50mg/kg) in
      adults rats induced epileptic seizure and increased activation of caspase-3 and
      caused neuronal death. Further, rats were injected with vit-C (250 mg/kg) 30 min
      before PTZ injection. The protective effect of vit-C against PTZ-induced
      apoptotic neurodegeneration in adult rat brain was observed using Western blot
      analysis and Nissl staining. The results showed that conclusive dose of PTZ
      induced seizure, increased expression of caspase-3 and neuronal apoptosis in
      adult rat brain. Whereas, the pretreatment of vit-C along with PTZ showed
      significantly decreased expression of caspase-3 as compare to control group.
      Finally, our results indicated that vit-C can prevent some of the deleterious
      effect of seizure and neuronal degeneration induced by PTZ in adult rat brain.

PMID- 21715259
TI  - Antimicrobial activity of Bacillus sp. strain FAS1 isolated from soil.
AB  - During screening for antibiotic producing microorganisms from environmental soil
      samples, the supernatant of a bacterial isolate was found to have antibacterial
      and antifungal activity on the standard indicator species. The standard cylinder
      plate method was used to determine the inhibitory effect of the crude supernatant
      of each isolate on 6 bacterial and 3 fungal standard strains by measuring the
      diameter of inhibition zone. The highest inhibition zone on Aspergillus niger
      belonged to culture broth of isolate FAS1 by 25 mm, and this isolate was the most
      efficient microorganism to inhibit standard bacterial and fungal species. Based
      on morphological and biochemical properties as well as 16S rDNA gene analysis,
      the selected isolate (isolate FAS(1)) belonged to Bacillus genus. Investigation
      on the ability of different culture media for antibiotic production led to select
      Luria-Bertani media for further studies. Treatment of the culture broth of the
      isolate FAS(1) using typical protease didn't decrease the antimicrobial activity
      of the supernatant. After extracting of culture broth of the selected isolate by
      ethyl acetate as an organic solvent, the inhibitory effect was mainly increased.
      More investigation was done by bioautography method where the ethyl acetate
      fraction of the broth culture was separated on TLC by chloroform:methanol, 60:40
      as mobile phase and R(f) were calculated for inhibition spots.

PMID- 21715260
TI  - Nutrient composition, phenolic content and free radical scavenging activity of
      some uncommon vegetables of Pakistan.
AB  - Vegetables play a vital role in the prevention of human disease and in the
      improvement of general health as these contain vitamins, amino acids, fiber,
      antioxidants and minerals. In the present study, some less familiar vegetables of
      Pakistan namely chickpea (leaves), chungah (shoots), drumstick tree
      (inflorescences), radish (fruit pods), mountain ebony (flower buds), mustard
      (leaves), purslane (leaves) and white goosefoot (leaves and shoots) were
      evaluated for proximate composition, mineral content, phenolic content and free
      radical scavenging activity. The protein, fat, fiber, carbohydrate and ash
      contents of the selected vegetables were in the range of 2.9 to 6.6%, 0.2 to
      2.5%, 2.4 to 8.6%, 9.7 to 20.1% and 1.0 to 2.3%, respectively. The concentration
      of vitamin C ranged between 32.6 to 120.1 mg/100 g. The phosphorus, calcium,
      iron, zinc, manganese, magnesium and copper were 190 to 3400, 103 to 987, 19 to
      93, 12 to 47, 9 to 121, 299 to 1635 and non detectable level to 42 mg/kg,
      respectively. The amount of total phenolic content varied from 55.3 to 221.0 mg/g
      in the dry methanolic extracts of the studied plants. The EC(50) values were
      below 1400 MUg/ml, indicating that all the studied vegetables have good
      scavenging effect on DPPH radical.

PMID- 21715261
TI  - Analysis of imatinib in bone marrow and plasma samples of chronic myeloid
      leukaemia patients using solid phase extraction LC-ESI-MS.
AB  - The LC-ESI-MS was developed and validated for the analysis of imatinib in plasma
      and bone marrow samples using deuterated imatinib (D(8)-IM) as an internal
      standard. The biological samples were extracted using Strata-X-C SPE cartridges
      and separated on C(8) column (50 x 3 mm, 3 MUm), and methanol: 0.1% formic acid
      (70:30) was delivered at the rate of 0.7 ml/min as a mobile phase. Imatinib was
      quantified in samples by monitoring the ions m/z 494.3 for imatinib and 502.3 for
      D(8)-imatinib on mass spectrometer. The method was linear in the concentration
      range of 1-1500 ng/250 MUl in spiked human plasma samples and limit of
      quantification was 5 ng/mL. Inter-day and intra-day variations in spiked human
      plasma spiked with 50, 250 and 500 ng /mL were less than 3.16%. The repeatability
      and reproducibility and other parameters of the methods were also validated. The
      method was employed for the analysis of the imatinib in human plasma and bone
      marrow samples. The drug levels in bone marrow and plasma samples were correlated
      to the degree of cytogenetic response. No significant difference of imatinib
      level between blood and bone marrow in IM-treated patients dosed to steady state
      was observed.

PMID- 21715262
TI  - Evaluation of phytoconstituents and anti-nephrotoxic and antioxidant activities
      of Monochoria vaginalis.
AB  - Monochoria vaginalis is an herbaceous medicinal plant used to treat, liver
      problems India. Acetaminophen is a commonly used analgesic and antipyretic agent
      which, at high doses, causes liver and kidney necrosis in man and animals. The
      aim of the present study is to evaluate phytoconstituents and investigate the
      nephroprotective & antioxidant activities of the ethanol extract of Monochoria
      vaginalis on acetaminophen induced toxicity in rats. Phytoconstituents like n
      hexadecanoic acid, 3-methyl- acetate-1-butanol, 1,1,3-triethoxy- propane, Z,Z,Z
      1,4,6,9 - nonadecatetraene, undecanoic acid, 3-trifluoroacetoxy penta decane and
      4-ethyl-5-octyl-2,2-bis (trifluoromethyl) - cis-1,3-dioxalone were identified
      from ethanol extract of Monochoria vaginalis by using a gas chromatograph-mass
      spectrograph (GC MS). Biochemical studies show that there is an increase in the
      levels of serum urea and creatinine along with an increase in the body weight and
      reduction in the levels of uric acid in acetaminophen induced groups. These
      values are retrieved significantly by treatment with Monochoria vaginalis
      extracts at two different doses. The antioxidant studies reveal that the levels
      of renal SOD, CAT, GSH and GPx in the APAP treated animals are increased
      significantly along with a reduced MDA content in ethanol extract of Monochoria
      vaginalis treated groups. Apart from these, histopathological changes also reveal
      the protective nature of the Monochoria vaginalis extract against acetaminophen
      induced necrotic damage of renal tissues. In conclusion, these data suggest that
      the ethanol extract of Monochoria vaginalis can prevent renal damage from APAP
      induced nephrotoxicity in rats and it is likely to be mediated through active
      phytoconstituents and its antioxidant activities.

PMID- 21715263
TI  - Evaluation of cefaclor oral suspensions stability using reversed phase high
      performance liquid chromatography and antimicrobial diffusion methods.
AB  - The effect of temperature stresses on Cefaclor suspensions under different
      storage conditions for a duration of 14 days was tested. The degradation of
      Cefaclor was determined on the 2nd, 7th and 14th day after reconstitution using a
      sensitive and precise Reversed phase High Performance Liquid Chromatographic (RP
      HPLC) method. The RSD values for Forticef, Midocef, Ceclor, Cefabac and Cloracef,
      indicated a good precision of the RP-HPLC method. The limit of detection (LOD)
      and the limit of quantification (LOQ) were found 0.008 mg/ml and 0.03mg/ml
      respectively. The antimicrobial effect of Cefaclor suspension was also tested
      against pathogenic bacteria using the cylinder diffusion method. The RSD values
      range of the antimicrobial assay for all the Cefaclor compounds were 1.47-3.7%.
      The LOD and LOQ were 0.2mg/ml and 1mg/ml respectively. During the normal use of
      Ceclor, Midocef, and Forticef the loss of activity and the degradation were less
      than 5% on the 14th day of preservation at 4 degrees C. However, the percentage
      of degradation for Cefabac and Cloracef on the 14th day reached 5 and 6%,
      respectively. Statistical multiple comparison between the effect of 4 degrees C
      and 25 degrees C indicated non significant mean differences (P>0.05) for
      Forticef, Cefabac, Ceclor and Cloraf and significant effect for Midocef (P
      <0.05). Significant effects were observed between (4oC and 37 degrees C) and (25
      degrees C and 37 degrees C) for all except Ceclor. Multiple comparisons between
      days of storage showed non significant mean difference values at 4 degrees C
      except Cefabac. However significant results between days were found at 25 degrees
      C and 37 degrees C except for Midocef between (7th and 14th day). It was found
      that the pediatric suspensions of Cefaclor in the Jordanian market were stable
      and contained the amount of active ingredient specified by the United States
      pharmacopoeias specification (USP) and the British Pharmacopoeias specifications
      (BP).

PMID- 21715264
TI  - Effects of apomorphine on locomotive activity and monoamine metabolism: a dose
      related study.
AB  - We have monitored dose dependent effects of apomorphine on motor activity and
      monoamine metabolism. Behavioral sensitization and craving, which develop upon
      repeated treatment with dopamine receptor agonist apomorphine, are major
      limitations of the therapeutic use of apomorphine in Parkinson's patients.
      Effects of single (intraperitoneal) injection of apomorphine at different doses
      (i.e., 1.0, 2.0 & 4.0 mg/kg) on exploration in a novel environment (open field)
      and locomotion in a familiar environment (home cage) were investigated. Results
      show significantly enhanced activity in home cage (monitored 5min post injection)
      in a dose dependent manner. However, no significant influence of apomorphine on
      exploration of open field was observed in the present study (monitored 15 min and
      40 min post injection). Animals were decapitated 1 hr post apomorphine injection
      and whole brains of animals were collected and stored at -70 degrees C. Biogenic
      amines (i.e., 5-Hydroxytryptamine and dopamine) and metabolites (i.e.,
      Dihydroxyphenylacetic acid, Homovanillic acid & 5-Hydroxyindoleacetic acid) were
      estimated by reverse phase High Performance Liquid Chromatography with
      electrochemical detector (HPLC-EC). Effect of low (1.0mg/kg) dose of apomorphine
      was found to be non-significant on 5-Hydroxytryptamine (5-HT), 5
      Hydroxyindoleacetic acid (5-HIAA) and dopamine (DA) levels. Moderate (2.0 mg/kg)
      dose of drug increased (p<0.05) levels of Homovanillic acid (HVA). Whereas, high
      (4.0 mg/kg) dose of apomorphine decreased Dihydroxyphenylacetic acid (DOPAC)
      levels. Results could be helpful in elucidating the effect of apomorphine at
      different doses and its implication for extending therapeutics in Parkinson's and
      related disorders.

PMID- 21715265
TI  - Pharmacological profile of Salvadora persica.
AB  - This work was conducted to investigate the various pharmacological activities of
      Salvadora. persica family Salvadoracea and that includes anti inflammatory,
      analgesic, CNS, bleeding and clotting time activity by oral administration at the
      dose of 300 and 500mg/kg of body weight in animal models. Acute oral toxicity
      results showed that crude extract of S. persica is safe up to the dose of 5g/kg
      body weight of animals. Carraganeen induced hind paw edema method for anti
      inflammatory activity, tail immersion test method for analgesic activity, Rota
      rod and grip strength test for CNS activity were carried out in animal models.
      The analgesic activity was compared with aspirin, 300mg/kg body weight, anti
      inflammatory activity was compared with indomethacine, 10mg/kg body weight,
      Transamin 250mg/kg and Vitamin K 10mg were used for bleeding and clotting time
      activity respectively while diazepam 5mg/kg were used as standard for behavior
      and CNS activities. In all activities S. persica showed prolonged and dose
      dependent effects. Phytochemical analysis was also carried out which showed the
      presence of certain phytoconstituents which possesses these properties. Therefore
      the results justified the traditional use of the plant.

PMID- 21715266
TI  - Antidiabetic and hypolipidemic effects of different fractions of Coccinia
      cordifolia L. on normal and streptozotocin-induced diabetic rats.
AB  - The present study was carried out to observe the antidiabetic and hypolipidemic
      effects of petroleum-ether, ethyl acetate and chloroform fractions isolated from
      ethanolic extract of the leaves of Coccinia cordifolia Linn. (150 mg/kg body
      weight) on normal and streptozotocin (STZ)-induced diabetic rats for one day
      experiment. Single doses (150 mg/kg, i.p.) of C. cordifolia extracts were given
      to normal and diabetic rats. The fasting blood glucose (FBG), serum triglyceride
      (TG) and serum total cholesterol (TC) levels were investigated in normal and STZ
      diabetic rats on 0, 1, 2, 3, 6, 10, 16, and 24th hours. In normoglycemic rats the
      pet-ether and ethyl acetate fractions of C. cordifolia reduced blood glucose
      level significantly (39.66% and 40.68% at 16th and 24th hour respectively). In
      the STZ-diabetic rats pet-ether and ethyl acetate fractions also reduced blood
      glucose level significantly (50.39% and 50% at 10th and 24th hour respectively).
      Ethyl acetate fraction is most effective which reduced total cholesterol level by
      31.04% and 36.69% in normal and STZ-diabetic rats respectively. Ethyl acetate
      fraction reduced triglyceride level by 43.82% and 42.01% in normal and STZ
      diabetic rats respectively. Our results indicate that pet-ether and ethyl acetate
      fractions of C. cordifolia have potentiality against diabetes.

PMID- 21715267
TI  - Interaction study of moxifloxacin and lomefloxacin with co-administered drugs.
AB  - Moxifloxacin and lomefloxacin are fluoroquinolone antibiotics used in treating
      urinary and respiratory tract infections. Fluoroquinolones are known to have
      interactions with drugs that are active in gastro intestinal tract. Being
      moxifloxacin and lomefloxacin fluoroquinolones the interaction study of was
      carried out with sucralfate, gelusil, erythromycin and multi minerals. The
      interaction was studied at neutral, acidic and basic conditions both at room
      temperature and 37 degrees C. The effect of dissolution medium simulating various
      body environments with response to pH has been examined in order to elucidate the
      interactions. The response of moxifloxacin and lomefloxacin after interaction
      with co-administered drugs at different conditions and temperature were noted
      using a Shimadzu HPLC system with PDA detector. It was seen that interaction of
      these fluoroquinolones was more at 37 degrees C than at room temperature.
      Moxifloxacin and Lomefloxacin reacts faster with sucralfate and gelusil in acidic
      media whereas with erythromycin in basic media and multi-minerals in neutral
      media. The study ensures the interaction of fluoroquinolones with selected class
      of drugs. In order to achieve the effective therapeutic effect appropriate time
      intervals between administrations of drugs is essential.

PMID- 21715268
TI  - Phytochemical analysis, antioxidant and antibacterial effects of sea buckthorn
      berries.
AB  - Sea buckthorn berries are therapeutically used as folk medicine for a variety of
      diseases, however, the scientific evidence is hardly available to support their
      role. This study explored their chemical constituents and their role as
      antioxidant and antibacterial agents. Three common solvents such as petroleum
      ether (40 degrees  - 60 degrees C), chloroform and methanol were successively
      used for the extraction of active principles from sea buckthorn berries. Five
      major fractions (F1-F5) were isolated from the active methanol extract by column
      and thin layer chromatography. An attempt was made to identify the chemical
      nature of pooled fractions by available spectral means. Antioxidant potential of
      methanol extract and its fractions was measured by DPPH, formation of
      phosphomolybdenum complex and TBA methods. The hole-plate diffussion method was
      used to find out the antibacterial activity. A very brief structure-activity
      relationship of the potent antioxidant and antimicrobial compounds is discussed.
      Methanolic extract and its fractions contain numerous phenolic compounds such as
      flavonoids, which may be responsible for antioxidant and antibacterial effects.

PMID- 21715269
TI  - Determination of toxic metals in some herbal drugs through atomic absorption
      spectroscopy.
AB  - This study presents a picture of occurrence of heavy metals (Pb, Cd, Cu, Cr, Co,
      Fe, Ni, Zn) in some selected valuable herbal drugs (G. glabra, O. bracteatum, V.
      odorata , F. vulgare, C. cyminum, C. sativum, and Z. officinalis) purchased from
      three different zones (southern, eastern, and western) of Karachi city using
      atomic absorption spectrophotometer. Heavy metal concentrations in these drugs
      were found in the range of: 3.26-30.46 for Pb, 1.6-4.91 for Cd, 0.65-120.21 for
      Cu, 83.74-433.76 for Zn, 1.61-186.75 for Cr, 0.48-76.97 for Ni, 5.54-77.97 for Co
      and 65.68-1652.89 ug/g for Fe. Percentage of heavy metals that were found beyond
      the permissible limits were: 71.4% for Pb, 28.51% for Cd, 14.2% for Cu, and 9.5 %
      for Cr. Significant difference was noticed for each heavy metal among herbal
      drugs as well as their zones of collection using two way ANOVA followed by least
      significant (LSD) test at p<0.05.Purpose of this research is to detect each type
      of heavy metal contaminant of herbal drugs by environmental pollution, as well as
      to highlight the health risks associated with the use of such herbal drugs that
      contain high levels of toxic heavy metals.

PMID- 21715270
TI  - Effects of aegeline, a main alkaloid of Aegle Marmelos Correa leaves, on the
      histamine release from mast cells.
AB  - Aegeline or N-[2-hydroxy-2(4-methoxyphenyl) ethyl]-3-phenyl-2-propenamide is a
      main alkaloid isolated from Aegle marmelos Correa collected in Yogyakarta
      Indonesia. In our study, we investigated the effects of aegeline on the histamine
      release from mast cell. The study was performed by using (1) rat basophilic
      leukemia (RBL-2H3) cell line, and (2) rat peritoneal mast cells (RPMCs). DNP(24)
      BSA, thapsigargin, ionomycin, compound 48/80 and PMA were used as inducers for
      histamine release from mast cell. In our study, aegeline inhibited the histamine
      release from RBL-2H3 cells induced by DNP(24)-BSA. Indeed, aegeline showed strong
      inhibition when RBL-2H3 cells induced by Ca(2+) stimulants such as thapsigargin
      and ionomycin. Aegeline is suggested to influence the intracellular Ca(2+) pool
      only since could not inhibit the (45)Ca(2+) influx into RBL-2H3 cells. Aegeline
      showed weak inhibitory effects on the histamine release from RPMCs, even though
      still succeed to inhibit when the histamine release induced by thapsigargin.
      These findings indicate that aegeline altered the signaling pathway related to
      the intracellular Ca(2+) pool in which thapsigargin acts. Based on the results,
      the inhibitory effects of aegeline on the histamine release from mast cells
      depended on the type of mast cell and also involved some mechanisms related to
      intracellular Ca(2+) signaling events via the same target of the action of
      thapsigargin or downstream process of intracellular Ca(2+) signaling in mast
      cells.

PMID- 21715271
TI  - Flavonoids of Enhydra Fluctuans exhibits analgesic and anti-inflammatory activity
      in different animal models.
AB  - Enhydra fluctuans (Compositae), an edible semi aquatic herbaceous vegetable
      plant, widely used in traditional system of Indian medicine. Total flavonoids of
      E. fluctuans (TFEF) were screened for analgesic and anti-inflammatory activity.
      Analgesic activity was studied in acetic acid induced writhing response and by
      hot plate method in Swiss albino mice. Anti-inflammatory activity was estimated
      by carrageenan and histamine induced acute inflammation and Freund's complete
      adjuvant (FCA) induced chronic inflammation in rats. Two flavonoids, baicalein 7
      O-glucoside and baicalein 7-O-diglucoside, were isolated from the ethyl acetate
      fraction. Oral administration of TFEF at the doses of 200 and 400 mg/kg provide
      27.05 and 55.49% protection respectively in acetic acid induced writhing method.
      It also increased the pain threshold in mice evidenced by hot plate method. TFEF
      showed more potent anti-inflammatory activity. The results of this study may be
      attributed to high free radical scavenging and antioxidant potential of the
      flavonoids present in ethyl acetate fraction of Enhydra fluctuans.

PMID- 21715272
TI  - Hepatoprotective studies on Haloxylon Salicornicum: a plant from Cholistan
      desert.
AB  - The objective was to study the in-vivo hepatoprotective effect of aerial parts of
      Haloxylon salicornicum (Moq.) Bunge (Family: Chenopodiaceae) in order to validate
      its traditional use in hepatobiliary disorders, by native people of Cholistan
      desert, Pakistan. Aerial parts (ethanolic extract) of Haloxylon salicornicum
      (HS), (500 and 750 mg/kg/day, p.o. for 7 days) were evaluated on CCl(4)
      intoxicated rabbits (0.75 ml/kg., s/c.) by serum biochemical parameters and liver
      histopathological observations. Silymarin (100 mg/kg/day, p.o. for 7 days) was
      used as a standard hepatoprotective drug. CCl(4) intoxicated group had elevated
      levels of SGOT, SGPT and ALP significantly but TB level was normal as compared to
      control group. HS extract (both doses of 500 and 750 mg/kg) showed
      hepatoprotective effect by significant restoration of SGOT, SGPT, ALP and TB
      levels as compared to CCl4 control. 500 mg/kg doses of HS extract produced more
      significant results as compared to 750 mg/kg doses and Silymarin.
      Histopathological examination of liver tissues further substantiated these
      findings. Therefore, outcome of the present study validate the traditional claims
      on hepatoprotective effects of Haloxylon salicornicum (aerial parts).

PMID- 21715273
TI  - Effects of dexamethasone and atorvastatin on atrial sodium current and its early
      tachycardia-induced electrical remodeling in rabbits.
AB  - PURPOSE: Atrial fibrillation (AF) results in tachycardia-induced ionic
      remodeling. Pharmacological prevention of tachycardia-induced ionic remodeling
      not only with "classical" antiarrhythmics but also with drugs which provide a
      basis for some of the pillars of the so-called "upstream" therapy of AF like
      corticosteroids or statins has been proposed as a therapeutic strategy. Amongst
      other ion currents, atrial sodium current I(Na) and its tachycardia-induced
      alterations play an important role in AF pathophysiology. Thus, effects of a
      dexamethasone (DT) and atorvastatin treatment (AT) on atrial sodium current I(Na)
      and its tachycardia-induced remodeling were studied in a rabbit model. METHODS: 9
      groups with 4 animals were examined. Atrial pacemaker leads were implanted in all
      animals. No rapid atrial pacing (600/min) was performed in the control group but
      for 24 or 120 hours in the respective pacing groups. Instrumentation and pacing
      did not differ from the respective drug groups but an additional treatment with
      dexamethasone or atorvastatin (7 days) was performed. RESULTS: Rapid atrial
      pacing (RAP, 600/min) reduced I(Na) after 24 hours (~ -50%) with no further
      reduction after 120 hours. DT reduced I(Na) (~ -20%), current densities in
      consecutively tachypaced animals did not differ from those in untreated animals.
      AT reduced INa similar as RAP, subsequent RAP did not further diminish I(Na).
      CONCLUSIONS: Impact of corticosteroids and statins on INa and its tachycardia
      induced alterations also contribute to the mode of action of these substances in
      upstream treatment of atrial fibrillation.

PMID- 21715274
TI  - Effect of natural honey on human platelets and blood coagulation proteins.
AB  - Present study was conducted to determine the effects of honey on blood
      hemostasis, in-vitro effect of honey was observed on platelet aggregation and
      blood coagulation employing, activated partial prothrombin time (aPTT),
      prothrombin time (PT), thrombin time (TT) and fibrinogen levels in blood. Honey
      samples showed moderate inhibition of platelet aggregation with IC(50) 5-7.5%.
      The coagulation assays showed that at higher concentrations (>15%) honey samples
      increased whole blood clotting time. When assayed in platelet poor plasma (PPP),
      honey samples significantly (P>0.005) prolonged aPTT, PT, and TT. The honey
      samples (at 3.75% and 7.5% concentrations) cause mean increment of aPTT = 19+/
      10% and 62+/-10%; PT 6+/-5% and 40+/-5%; TT 35+/-15% and 112+/-30% respectively.
      Moreover, PPP isolated from whole blood pre-incubated with honey samples (9.0%
      for 10 minutes) showed mean prolongation of aPTT, PT and TT of 45+/-21%, 26+/-9%
      and 105+/-24% respectively. Interestingly, incubation of honey at 6.25% and
      11.75% concentrations in PPP considerably (P>=0.005) reduced fibrinogen levels
      i.e. 13+/-4% and 86+/-30% respectively. The present study outlines the inhibitory
      effect of natural honey on platelet aggregation and blood coagulation. These
      observations provide first line data for modulatory role(s) of honey on process
      of hemostasis.

PMID- 21715275
TI  - Formulation and evaluation of Ficus glomerata mucilage sustained release matrix
      tablets of gliclazide.
AB  - The main aim of present investigation was to develop sustained release matrix
      tablets of Gliclazide using fruit mucilage from the plant Ficus glomerata.
      Varying ratios of drug and polymer viz. 1:0.25, 1:0.5, 1:0.75, 1:1.0 and 1:1.25
      were selected for the study. The flow properties of powdered mucilage and
      physical properties of matrix tablets were performed. The swelling behavior and
      release rate characteristics were studied. The in vitro drug release data was
      analyzed by zero order, first order, Higuchi plot, Peppas plot and Hixon-Crowell
      Models. It was observed that as the proportion of mucilage increased the release
      of drug from the matrix tablets was retarded. Stability studies were conducted at
      40+/-2oC and RH 75+/-5% for 3 months indicates that Gliclazide was stable in the
      matrix tablets. The Differential Scanning Calorimetric (DSC) and Fourier
      Transform Infrared (FTIR) study revealed that there was no negative chemical
      interaction between drug and the mucilage used. From the dissolution study, it
      was concluded that dried Ficus glomerata mucilage can be used as an excipient for
      making sustained release matrix tablets.

PMID- 21715276
TI  - Anti-inflammatory and analgesic activities of ethanolic extract of Sphaeranthus
      indicus Linn.
AB  - The aim of the present study was to evaluate the intensity of the anti
      inflammatory and analgesic activities of Sphaeranthus indicus on albino mice and
      rat of either sex. The flowers of S. indicus are an important herb used in folk
      eastern medicines. In this study, the ethanolic extract of S. indicus in doses of
      300 and 500 mg/kg was used. Anti-inflammatory activity was evaluated by measuring
      the mean decrease in hind paw volume after the sub planter injection of
      carrageenan. The analgesic activity was tested against acetic acid induced
      writhing response using albino rats. Result of the study shows that at the end of
      one hour the inhibition of paw edema was 42.66 and 50.5% respectively and the
      percentage of protection from writhing was 62.79 and 68.21 respectively. S.
      indicus possesses several important pharmaceutical and pharmacological
      properties. The current study describes that flower of S. indicus has significant
      anti-inflammatory and analgesic properties. Conclusion of the study is that this
      herbal medicine can be used as an alternative therapy for the treatment of minor
      to moderate types of inflammation and as a painkiller.

PMID- 21715277
TI  - Anti lipid peroxidation activity of Piper trioicum Roxb. and Physalis minima L.
      extracts.
AB  - Attempt has been made to evaluate free radical scavenging activity of ethanolic
      extract of Piper trioicum Roxb. and Physalis minima L. individually. In this
      study goat liver has been used as lipid source. This in vitro evaluation was done
      by measuring the malondialdehyde (MDA) of tissue homogenates. The results suggest
      that the ethanolic extract of the Piper trioicum Roxb. and Physalis minima L. has
      the ability to suppress the lipid peroxidation and it was also found that Piper
      trioicum Roxb. extract has more activity than Physalis minima L. extract.

PMID- 21715278
TI  - Investigations on the triiodothyronine (T3)-specificity of thyrotropic (TSH) and
      gonadotropic (HCG) hormone in the unicellular Tetrahymena.
AB  - In a previous experiment thyrotropin (TSH) increased the triiodothyronine (T3)
      production of Tetrahymena and chorionic gonadotropin (HCG) moderately overlapped
      the effect. At present the production of three amino acid type (histamine,
      serotonin, epinephrine) and one peptide (endorphin) hormones were studied under
      the effect of TSH or HCG, in tryptone-yeast (TY) or salt (Losina-Losinsky)
      medium. The duration of the effect was 10 min. TSH significantly (with almost
      20%) decreased epinephrine production in TY medium and HCG similarly decreased
      epinephrine and increased histamine level. In salt solution TSH as well as HCG
      decreased the level of serotonin. The results show that at this low level of
      phylogeny TSH effect is not completely thyroxine-specific, however it is not
      general. HCG overlaps TSH effect on epinephrine and serotonin production, however
      its effect is broader. The experiments also demonstrate that the effect of
      pituitary trop-hormones can be bidirectional in Tetrahymena, as histamine level
      was increased and epinephrine level was decreased by HCG, in the same cells.

PMID- 21715279
TI  - Preliminary evidence on photoreactivation of Frankia spores with visible light
      after exposure to UV-C radiation.
AB  - Spores of four Frankia strains, the nitrogen-fixing actinomycete, were exposed to
      short wavelength UV-C radiation of 254 nm at 1 lux cm(2) (0.24 mw cm2 of energy)
      for 10 min. The used strains were HFP020203, UGL020604, UGL020602q and ORS021001.
      Exposure to UV was followed by reactivation with visible white light at 327.4 lux
      cm(2) for the same period of time. Spore germination percentage, spore protein
      content, and cell growth were damaged by this treatment. The lower and higher
      percentages of reduction in spore germination were 32 and 63% and, for the same
      strains, the recovery by white light was 7.2 and 37%. The lower percentages of UV
      damage and subsequent low recovery were recorded for strain ORS021001 that is
      considered more resistant to UV than the other strains. The higher percentages
      were recorded for strain HFP020203 that is more sensitive to UV but having more
      efficient repairing mechanisms. All the tested strains showed repairing activity
      induced by white light as indicated from the increase in their spore germination,
      protein content and almost restoring the normal shape of Frankia hyphae, after
      being damaged, as revealed by scanning electron microscope. This is the first
      evidence that photo-repairing systems are present in Frankia strains although
      there are variations in their response to both UV-C and photoreactivation by
      white light.

PMID- 21715280
TI  - Cerumen as a potential risk for transmission of Hepatitis B virus.
AB  - Hepatitis B virus (HBV) transmission via blood and other body fluids from
      infected individuals to healthy people has been largely demonstrated. However, in
      the current literature, there is little information available on the potential
      role of cerumen in HBV transmission. Cerumen and blood were collected from 70
      patients infected with HBV and 70 volunteer healthy people were selected as the
      control group, and the samples were evaluated by ELISA and Real-time PCR. All the
      patients proved positive for HBsAg and anti HBc total. Sixty-one of the 70
      cerumen samples of cases (82.1%) and 5 (7%) of controls were positive for HBV DNA
      with ranges from 1.53 * 102 to 2.9 * 108 and 1.3 * 102-2.6 * 105/ml,
      respectively. In three patients, the level of HBV DNA in cerumen was higher than
      that in the serums. The patients who were positive for HBeAg showed a higher rate
      of HBVDNA in the serum and cerumen.The results of this study showed the level of
      HBV DNA as a probably indicator of high risk transmission factor, which was
      present in the cerumen of chronic hepatitis B patients in west of Iran.

PMID- 21715281
TI  - Characterization of Staphylococcus aureus strains isolated from raw milk of
      bovine subclinical mastitis in Tehran and Mashhad.
AB  - Staphylococcus aureus is considered one of the most important food borne
      pathogens. A total of 111 isolates of S. aureus were cultured from raw milk
      samples during January 2009 to June 2009 from Tehran and Mashhad. The coagulase
      gene polymorphism and the prevalence of classical enterotoxin genes of S. aureus
      strains were determined by PCR-RFLP (restriction fragment length polymorphism)
      and Multiplex-PCR. Disk diffusion method was used to determine the susceptibility
      of isolates to antimicrobial agents as instructed by Clinical and Laboratory
      Standards Institute. Sixty-seven % of the isolates harboured one or more
      enterotoxin genes. The most prevalent gene was sec, found in 59 % of the
      isolates. Approximately 8% of the isolates were positive for sea, seb and sed
      genes. Only one isolate had see gene. The rate of coexistence of enterotoxin
      genes was 14%. All S. aureus isolates were susceptible to ciprofloxacin,
      gentamicin, imipenem, minocycline, oxacillin and vancomycin. They were resistant
      to ampicillin (64%), penicillin (56%), clindamycin (22%), tetracycline (22%),
      doxycycline (19%), teicoplanin (13%), rifampin (2%) and trimethoprim
      sulfamethoxazole (2%). On the basis of coagulase gene analysis of 111 S. aureus
      isolates, the PCR products of 56 isolates were digested with Alu I that produced
      three distinct patterns. These data indicate the high prevalence of
      enterotoxigenic S. aureus in raw bovine milk in Tehran and Mashhad, and highlight
      the importance of proper quality control of dairy products for public health.

PMID- 21715282
TI  - Vaccination with DNA vector expressing chlamydial low calcium response protein E
      (LcrE) against Chlamydophila pneumoniae infection.
AB  - Chlamydophila pneumoniae is an obligate intracellular human pathogen, which
      causes acute respiratory tract infections and can also cause chronic infections.
      C. pneumoniae possess type III secretion system (TTSS), which allows them to
      secrete effector molecules into the inclusion membrane and the host cell cytosol.
      Low calcium response protein E (LcrE) is a part of TTSS. The gene of LcrE in a
      6His-tagged form was cloned from C. pneumoniae CWL029, expressed and purified
      from Escherichia coli using the HIS-select TALON CellThru Resin, this gene was
      also cloned into a eukaryotic expression vector (pDeltaRC). One group of BALB/c
      mice received an intramuscular pDeltaRC inoculation then the mice were immunized
      with purified LcrE protein; the second group of mice was immunized two times with
      the recombinant plasmid (pDeltaRCLcrE), and the third group was primed with
      pDeltaRCLcrE inoculation then boosted with LcrE protein. LcrE-specific antibody
      response was induced by DNA immunization with a shift towards Th1 isotype pattern
      compared to protein-immunization, this shifting pattern was observed in plasmid
      primed then protein-boosted animals. DNA immunization given as a priming and
      followed by a protein booster significantly reduced the number of viable bacteria
      in the lungs after challenge with C. pneumoniae. These results confirm that
      immunization with pDeltaRCLcrE can be an effective part of a vaccination schedule
      against C. pneumoniae.

PMID- 21715283
TI  - Curiosities of the methicillin-resistant Staphylococcus aureus survey -
      possibility of pseudo-outbreak and transmission to household contacts.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is currently one of the most
      prevalent antibiotic-resistant pathogens in hospitals, but it is also emerging as
      a community-acquired pathogen. We analysed the clinical and microbiological data
      of the patients in a county teaching hospital regarding MRSA. During the
      examination period (1996-2010), four outbreaks and one pseudo-outbreak occurred.
      It also became evident that health care workers and their families are possibly
      at risk of becoming carriers of MRSA. The importance of the molecular
      epidemiological investigation (pulsed-field gel-electrophoresis (PFGE)) typing
      and hygienic measures in order to detect and control MRSA outbreaks must be
      emphasised. Following infection control guidelines seems to be cost-effective
      method of controlling the nosocomial transmission of MRSA.

PMID- 21715284
TI  - Risk factors and prevalence of Demodex mites in young adults.
AB  - Demodex mites are ectoparasites often found in follicles of facial skin. Their
      role in human diseases is under investigation, and a growing number of studies
      indicated that they contribute to chronic inflammatory conditions of the skin,
      such as rosacea, blepharitis, otitis externa, alopecia and folliculitis. In our
      study we tested 96 healthy adults for the presence of Demodex mites. Risk factors
      influencing presence of mites and skin types of the tested individuals were
      evaluated. We found Demodex folliculorum or Demodex brevis in 17.7% of the
      samples, more frequently in males (21.9%) and in older adults (20%). Use of make
      up seems to reduce the likelihood of Demodex carriage, while pet ownership, use
      of shared items and living in close contact with older adults had no significant
      influence of presence of mites. Demodex positive individuals described their skin
      to be drier, more prone to erythema, but less for folliculitis compared to
      Demodex negative subjects.

PMID- 21715285
TI  - Serologic evidence of West Nile virus infection in patients with exanthema in
      Hungary.
AB  - The presence of WNV in Europe has been well known for decades, although the first
      human infections and avian outbreaks were diagnosed in Hungary only in 2003. An
      annual average of 6-8 cases of the neuroinvasive form of WNV infection has been
      detected in the region since then, but a higher number (17) of WNV associated
      neuroinvasive disease occurred in 2008. In 2004, a surveillance system was
      established for monitoring WNV-associated meningo-encephalitis cases in Hungary,
      but a milder type of illness (with fever, rash and/or influenza like symptoms) is
      not followed. Fifty-two sera of 45 patients with mild clinical symptoms (fever,
      exanthema) were tested for anti-WNV antibodies in 2008 in a retrospective study
      by immunofluorescence test and ELISA. Seven patients had antibodies against WNV,
      serologic evidence of recent WNV infection was found in 4 out of the 7 patients.
      Infections could be acquired predominantly in August and in September, which
      seems to be a risk period for WNV in Hungary. The possibility of a recent WNV
      infection should be taken into consideration in the occurrence of fever and rush
      at late summer. Differential diagnosis of exanthematous patients should include
      WNV serology tests and should be done routinely.

PMID- 21715286
TI  - Older adults with multi-morbidity: medication management processes and design
      implications for personal health applications.
AB  - BACKGROUND: Older adults often have multiple chronic problems requiring them to
      manage complex medication regimens overseen by various clinicians. Personal
      health applications (PHAs) show promise assisting in medication self-management,
      but adoption of new computer technologies by this population is challenging.
      Optimizing the utility of PHAs requires a thorough understanding of older adults'
      needs, preferences, and practices. OBJECTIVE: The objective of our study was to
      understand the medication self-management issues faced by older adults and
      caregivers that can be addressed by an electronic PHA. METHODS: We conducted a
      qualitative analysis of a series of individual and group semistructured
      interviews with participants who were identified through purposive sampling.
      RESULTS: We interviewed 32 adult patients and 2 adult family caregivers. We
      identified 5 core themes regarding medication self-management challenges: seeking
      reliable medication information, maintaining autonomy in medication treatment
      decisions, worrying about taking too many medications, reconciling information
      discrepancies between allopathic and alternative medical therapies, and tracking
      and coordinating health information between multiple providers. CONCLUSIONS: This
      study provides insights into the latent concerns and challenges faced by older
      adults and caregivers in managing medications. The results suggest that PHAs
      should have the following features to accommodate the management strategies and
      information preferences of this population: (1) provide links to authoritative
      and reliable information on side effects, drug interactions, and other medication
      related concerns in a way that is clear, concise, and easy to navigate, (2)
      facilitate communication between patients and doctors and pharmacists through
      electronic messaging and health information exchange, and (3) provide patients
      the ability to selectively disclose medication information to different
      clinicians.

PMID- 21715288
TI  - Modification of phenotypic and functional gender in the monoecious Arum italicum
      (Araceae).
AB  - Other than studies on sex-labile Arisaema species, studies of gender patterns in
      Araceae are scarce. The modification of phenotypic and functional gender was
      investigated in three populations of the monoecious Arum italicum Miller. The
      probability of reproduction and the number of inflorescences produced increased
      with plant size, and flower number (total, male, staminodes, female, pistillodes)
      increased with both plant and inflorescence sizes. However, plant and
      inflorescence sizes were poor predictors of floral sex ratio (female to male
      flower ratio). In contrast, change in floral sex ratio towards increasing
      femaleness was found among inflorescences sequentially produced by a plant. This
      change could not be explained by either a decrease in inflorescence size or a
      change in the mating environment. Differences in functional gender did not appear
      to be related to plant size or stage in the flowering period. Instead, different
      patterns of functional gender were found between plants with different number of
      inflorescences. Multi-inflorescence plants showed a functional gender around 0.5,
      while plants with one inflorescence showed a more extreme functional gender
      (either male, female, or functionally sterile). Sex of flowers in this species
      did not seem to exhibit a phenotypic trade-off.

PMID- 21715287
TI  - A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and
      lipodystrophy in the rat.
AB  - The Lpin1 gene encodes the phosphatidate phosphatase (PAP1) enzyme Lipin 1, which
      plays a critical role in lipid metabolism. In this study we describe the
      identification and characterization of a rat model with a mutated Lpin1 gene
      (Lpin1(1Hubr)), generated by N-ethyl-N-nitrosourea mutagenesis. Lpin1(1Hubr) rats
      are characterized by hindlimb paralysis and mild lipodystrophy that are
      detectable from the second postnatal week. Sequencing of Lpin1 identified a point
      mutation in the 5'-end splice site of intron 18 resulting in mis-splicing, a
      reading frameshift, and a premature stop codon. As this mutation does not induce
      nonsense-mediated decay, it allows the production of a truncated Lipin 1 protein
      lacking PAP1 activity. Lpin1(1Hubr) rats developed hypomyelination and mild
      lipodystrophy rather than the pronounced demyelination and adipocyte defects
      characteristic of Lpin1(fld/fld) mice, which carry a null allele for Lpin1.
      Furthermore, biochemical, histological, and molecular analyses revealed that
      these lesions improve in older Lpin1(1Hubr) rats as compared with young
      Lpin1(1Hubr) rats and Lpin1(fld/fld) mice. We observed activation of compensatory
      biochemical pathways substituting for missing PAP1 activity that, in combination
      with a possible non-enzymatic Lipin 1 function residing outside of its PAP1
      domain, may contribute to the less severe phenotypes observed in Lpin1(1Hubr)
      rats as compared with Lpin1(fld/fld) mice. Although we are cautious in making a
      direct parallel between the presented rodent model and human disease, our data
      may provide new insight into the pathogenicity of recently identified human LPIN1
      mutations.

PMID- 21715289
TI  - Ovule and seed development of Lacandonia schismatica (Lacandoniaceae).
AB  - Ovule and seed development is described for Lacandonia schismatica, a species
      whose androecium is surrounded by the gynoecium. The ovule in each carpel is
      basal, anatropous, tenuinucellate, and bitegmic. The female gametophyte is formed
      by the micropylar megaspore cell, after a coenocytic stage of the four megaspore
      nuclei. The mature female gametophyte has the normal complement of seven cells
      and eight nuclei. We propose a new type of female gametophyte development on the
      basis of the coenocytic stage of the tetrad, the cellularization of the tetrad,
      and the survival of the micropylar spore. At seed dispersal time, the embryo has
      ~10-20 cells. Endosperm development is of the nuclear type. At maturity,
      endosperm cells show starch and protein inclusions as well as polysaccharides in
      their thick walls. The seed coat is formed from the outer integument; the inner
      one disappears. The exotesta contains tannin. The fruit (achene) wall is two
      layered. The maturation of the fruits in a flower is synchronous, and they
      separate from the receptacle for dispersal.

PMID- 21715290
TI  - Biomechanics and functional anatomy of hollow-stemmed sphenopsids. I. Equisetum
      giganteum (Equisetaceae).
AB  - The hollow stem of Equisetum giganteum owes its mechanical stability to an outer
      ring of strengthening tissue, which provides stiffness and strength in the
      longitudinal direction, but also to an inner lining of turgid parenchyma, which
      lends resistance to local buckling. With a height >2.5 m isolated stems are
      mechanically unstable. However, in dense stands individual stems support each
      other by interlacing with their side branches, the typical growth habit of semi
      self-supporters.

PMID- 21715291
TI  - Pattern of morphological variation and diversity of Cocos nucifera (Arecaceae) in
      Mexico.
AB  - The pattern of morphological variation of Cocos nucifera in Mexico was
      statistically and numerically evaluated. Forty-one populations were analyzed,
      using 17 morphological fruit characters. Principal components and cluster
      analyses indicated four main groups of coconut populations that showed high
      similarity with four different genotypes recently imported into Mexico from areas
      that could be the origin of Mexican coconut populations. These four genotypes
      were evaluated with regard to the lethal yellowing disease in Jamaica and showed
      a differential susceptibility. Therefore it is possible to speculate upon a
      difference in susceptibility of the Mexican genotypes. The analysis of
      correlation between morphological and geographical distances showed a high
      positive correlation that supports: (1) historical evidence that indicates early
      introductions of coconut from different regions of the world, (2) that on both
      coasts of Mexico two different patterns of dispersal were involved: continuous
      and in jumps. Collectively these results suggest that the impact of the lethal
      yellowing disease on coconut populations will vary depending on the specific area
      and the origin of its coconuts.

PMID- 21715292
TI  - Osmunda (Osmundaceae) from the Triassic of Antarctica: an example of evolutionary
      stasis.
AB  - Compressed specimens of the fern Osmunda are described from the Triassic of the
      Allan Hills, Antarctica. The specimens consist of a once pinnate, deeply
      pinnatifid fertile frond as well as several sterile specimens. Six pinnae are
      present on the partial fertile rachis, with two sterile pinnae above four fertile
      pinnae. Both sterile and fertile specimens are virtually identical to the modern
      species Osmunda claytoniana. Entire fronds are fragmentary; the longest is 21 cm
      in length. Sterile pinnae are alternate and deeply pinnatifid, with slightly
      toothed pinnules and dichotomous venation. Fertile pinnae are 1-1.3 cm long, once
      pinnate, and lack vegetative lamina. Sporangia are clustered, each 300-375 um in
      diameter, and possess a transverse annulus 6-8 cells long; dehiscence is by a
      vertical slit. Fronds arise from a rhizome 4 cm long by 1 cm wide; two croziers
      are present on the rhizome. Two frond segments up to 6 cm long and three deeply
      pinnatifid pinnae are present on the uppermost part of one rachis. Pinnules are
      ~4 mm long and 2-3 mm wide. The presence of this Osmunda species in the Triassic
      demonstrates stasis of frond morphology, both fertile and vegetative, for the
      genus.

PMID- 21715293
TI  - Flower morphometry of Rhizophora mangle (Rhizophoraceae): geographical variation
      in Mexican populations.
AB  - We explored the patterns of intra- and interpopulation variation in flower
      morphology of the red mangrove, Rhizophora mangle. Twelve populations in Mexico
      were studied: five from the Gulf of Mexico and the Caribbean Sea, and seven from
      the Pacific Coast. Six metric floral attributes were measured from a sample of
      1370 flowers. Significant differences among populations were found for all six
      attributes. Because floral attributes were all correlated, scores derived from
      principal factor analysis were used to describe the variation in flower
      morphology. Two factors explained essentially all of the variance in flower
      morphology. Corolla and calyx size had a strong effect on factor 1, while
      gynoecium size had the higher effect on factor 2. Nested analyses of variance on
      the scores from both factors revealed significant differences among coasts, among
      populations within coasts, and among plants within populations. Nonetheless, this
      variation cannot be explained as a result of clinal variation, as indicated by a
      series of regression analyses. Cluster analysis (UPGMA) showed that a population
      from the Pacific coast was clustered together with those of the Atlantic, and the
      arrangement of populations within each coast showed no evident geographical
      pattern. We propose that frequent events of extinction and recolonization by a
      few individuals, followed by selfing, may produce differentiation among
      populations of red mangrove.

PMID- 21715294
TI  - Association between generalized anxiety disorder and asthma morbidity.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is common among people with
      asthma, but its association with asthma morbidity remains unexplored. This study
      examined cross-sectional associations between GAD and asthma control, quality of
      life, and self-efficacy. METHODS: Seven hundred ninety-four adults with confirmed
      asthma were recruited from the outpatient clinic of a university hospital.
      Patients underwent a sociodemographic and medical history interview (to assess
      health service use and medications), followed by a brief psychiatric interview
      (Primary Care Evaluation of Mental Disorders) to assess GAD. Patients completed
      questionnaires assessing asthma control, quality of life, and asthma self
      efficacy and underwent spirometry. General linear models and logistic regression
      were used to assess associations between GAD and asthma morbidity measures,
      adjusting for covariates. RESULTS: GAD affected 4% of the sample. The analyses
      revealed significant associations between GAD and worse overall asthma control
      (beta = 0.62, standard error [SE] = 0.18, p < .001), increased bronchodilator use
      (beta = 10.60, SE = 2.64, p < .001), worse asthma quality of life (beta = -0.91,
      SE = 0.23, p < .001), and worse asthma self-efficacy (beta = -59.56, SE = 13.59,
      p < .001) after the adjustment for covariates. Separate sensitivity analyses
      including major depressive disorder and asthma self-efficacy as additional
      covariates rendered many of these associations nonsignificant. There were no
      associations between GAD and emergency visits or hospitalizations. CONCLUSIONS:
      GAD is associated with worse asthma morbidity independent of age, sex, smoking,
      and asthma severity; however, comorbid major depressive disorder and low asthma
      self-efficacy may account for many of these associations. Only breathlessness and
      the frequency of bronchodilator use were uniquely associated with GAD. Future
      research should examine whether treatment of GAD can affect asthma outcomes.

PMID- 21715295
TI  - Posttraumatic stress disorder in anorexia nervosa.
AB  - OBJECTIVES: Comorbidity among eating disorders, traumatic events, and
      posttraumatic stress disorder (PTSD) has been reported in several studies. The
      main objectives of this study were to describe the nature of traumatic events
      experienced and to explore the relationship between PTSD and anorexia nervosa
      (AN) in a sample of women. METHODS: Eight hundred twenty-four participants from
      the National Institutes of Health-funded Genetics of Anorexia Nervosa
      Collaborative Study were assessed for eating disorders, PTSD, and personality
      characteristics. RESULTS: From a final sample of 753 women with AN, 13.7% (n =
      103) met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      criteria for PTSD. The sample mean age was 29.5 (standard deviation = 11.1)
      years. In pairwise comparisons across AN subtypes, the odds of having a PTSD
      diagnosis were significantly lower in individuals with restricting AN than
      individuals with purging AN without binge eating (odds ratio = 0.49, 95%
      confidence interval = 0.30-0.80). Most participants with PTSD reported the first
      traumatic event before the onset of AN (64.1%, n = 66). The most common traumatic
      events reported by those with a PTSD diagnosis were sexually related traumas
      during childhood (40.8%) and during adulthood (35.0%). CONCLUSIONS: AN and PTSD
      do co-occur, and traumatic events tend to occur before the onset of AN.
      Clinically, these results underscore the importance of assessing trauma history
      and PTSD in individuals with AN and raise the question of whether specific
      modifications or augmentations to standard treatment for AN should be considered
      in a subgroup to address PTSD-related psychopathology.

PMID- 21715296
TI  - The association between habitual diet quality and the common mental disorders in
      community-dwelling adults: the Hordaland Health study.
AB  - OBJECTIVE: Recent evidence suggests a role for diet quality in the common mental
      disorders depression and anxiety. We aimed to investigate the association between
      diet quality, dietary patterns, and the common mental disorders in Norwegian
      adults. METHODS: This cross-sectional study included 5731 population-based men
      and women aged 46 to 49 and 70 to 74 years. Habitual diet was assessed using a
      validated food frequency questionnaire, and mental health was measured using the
      Hospital Anxiety and Depression Scale. RESULTS: After adjustments for variables
      including age, education, income, physical activity, smoking, and alcohol
      consumption, an a priori healthy diet quality score was inversely related to
      depression (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.59-0.84) and
      anxiety (OR = 0.77, 95% CI = 0.68-0.87) in women and to depression (OR = 0.83,
      95% CI = 0.70-0.99) in men. Women scoring higher on a healthy dietary pattern
      were less likely to be depressed (OR = 0.68, 95% CI = 0.57-0.82) or anxious (OR =
      0.87, 95% CI = 0.77-0.98), whereas men were more likely to be anxious (OR = 1.19,
      95% CI = 1.03-1.38). A traditional Norwegian dietary pattern was also associated
      with reduced depression in women (OR = 0.77, 95% CI = 0.64-0.92) and anxiety in
      men (OR = 0.77, 95% CI = 0.61-0.96). A western-type diet was associated with
      increased anxiety in men (OR = 1.27, 95% CI = 1.14-1.42) and women (OR = 1.29,
      95% CI = 1.17-1.43) before final adjustment for energy intake. CONCLUSIONS: In
      this study, those with better quality diets were less likely to be depressed,
      whereas a higher intake of processed and unhealthy foods was associated with
      increased anxiety.

PMID- 21715298
TI  - Stress-induced respiratory pattern changes in asthma.
AB  - OBJECTIVES: To build upon prior research on stress-related breathing pattern
      changes in asthma. Previous research has considered a limited set of respiratory
      parameters and has remained equivocal. Emotions and stress are known to change
      the respiratory pattern. In asthma, certain breathing patterns have adverse
      effects on the airways and lead to symptom exacerbation. METHODS: We studied
      respiration during resting conditions and an acute psychosocial stressor (a free
      speech and mental arithmetic task) in participants with asthma (n = 20) and
      healthy controls (n = 19). The respiratory pattern was recorded with respiratory
      inductance plethysmography. Partial pressure of end-tidal carbon dioxide (PCO(2))
      was measured with capnometry before and after stress. RESULTS: The overall minute
      ventilation was higher in asthma (mean [standard deviation] = 9.0 [4.0] L versus
      6.8 [4.1] L, p < .05), but levels of the PCO(2) were comparable (34.6 [3.5] mm Hg
      versus 35.0 [3.7] mm Hg, p = .667) to healthy controls during prestress and
      poststress phases. Participants with asthma also showed a significant lengthening
      of inspiration, expiration, and the total respiratory cycle during stress
      compared with healthy controls (p < .05). During stress tasks, all participants
      showed marked increases in tidal volume, inspiratory flow, minute ventilation,
      tidal volume instability, ribcage contribution to tidal volume, and ribcage
      abdominal asynchrony. A significant increase in tidal volume instability and a
      tendency toward lengthening of expiration and the total respiratory cycle were
      observed in quiet-sitting periods at prestress to poststress in asthma.
      CONCLUSIONS: Expiratory lengthening and variable tidal volumes are characteristic
      for individuals with asthma during psychosocial stress. The function and possible
      association of these changes with symptom exacerbations require further study.

PMID- 21715297
TI  - Is heart rate variability related to memory performance in middle-aged men?
AB  - OBJECTIVE: Heart rate variability (HRV), a measure of autonomic function, has
      been associated with cognitive function, but studies are conflicting. Previous
      studies have also not controlled for familial and genetic influences. METHODS: We
      performed power spectral analysis on 24-hour ambulatory ECGs in 416 middle-aged
      male twins from the Vietnam Era Twin Registry. Memory and learning were measured
      by verbal and visual Selective Reminding Tests (SRTs). Mixed-effect regression
      models were used to calculate associations between and within twin pairs, while
      adjusting for covariates. RESULTS: The mean age (standard deviation) was 55 (2.9)
      years. A statistically significant positive association was found between
      measures of HRV and verbal, but not visual, SRT scores. The most statistically
      significant unadjusted association was found between very low frequency HRV and
      verbal total recall SRT, such that each logarithm of increase in very low
      frequency was associated with an increased verbal SRT score of 4.85 points (p =
      .002). The association persisted despite the adjustment for demographic and
      cardiovascular risk factors, and after accounting for familial and genetic
      factors by comparing twins within pairs. A significant interaction was found
      between posttraumatic stress disorder (PTSD) and HRV, such that total power and
      ultra low frequency were associated with SRT in twins (n = 362) without PTSD, but
      not in those with PTSD. CONCLUSIONS: Lower frequency spectra of HRV are
      associated with verbal, but not visual, learning and memory, particularly in
      subjects without PTSD. This association may indicate that autonomic nervous
      system dysregulation plays a role in cognitive decline.

PMID- 21715299
TI  - Multiwave associations between depressive symptoms and endothelial function in
      adolescent and young adult females.
AB  - OBJECTIVE: Depression has been linked to endothelial dysfunction, and some
      research suggests that past depressive episodes are associated with a lasting,
      negative impact on the endothelium. However, investigations in this area have
      been predominantly cross-sectional, raising questions about the direction of
      these associations. Using a multiwave design, we sought to extend previous
      research in this area by examining whether depressive symptoms have a lasting
      negative influence on endothelial function. METHODS: A total of 135 adolescent
      and young adult females with no known or suspected major health problems were
      followed for 21/2 years. Endothelial function was assessed at three time points
      throughout the study. The Beck Depression Inventory was administered, and
      information about health practices was collected every 6 months. RESULTS: Self
      reported depressive symptoms covaried with endothelial functioning on a within
      person basis (beta = -0.23, p < .05). As a participant's depression symptoms rose
      beyond her typical level, her endothelial function declined commensurately. This
      association persisted after controlling for health practices and adiposity. There
      was no evidence that depressive symptoms predicted endothelial function at later
      time points or interacted with time to predict the trajectories of endothelial
      function over the follow-up period. CONCLUSIONS: Depressive symptoms were
      concurrently associated with endothelial function in this cohort of healthy
      adolescent girls and young women. On visits when participants endorsed depressive
      symptoms that were higher than their mean level of depression, they tended to
      have worse endothelial function. We did not observe a lasting negative effect of
      depression on endothelial function.

PMID- 21715300
TI  - Association between depression and inflammation--differences by race and sex: the
      META-Health study.
AB  - OBJECTIVE: To test whether the association between depression and inflammation
      differs by race and sex. Depressive symptoms have been associated with higher
      levels of C-reactive protein (CRP). However, few studies have examined this
      association in samples including a significant number of African Americans, or
      examined whether the association differs by race and sex. METHODS: Depressive
      symptoms and CRP were assessed in 512 African American and white participants,
      age 30 to 65 years, as part of the community-based Morehouse and Emory Team up to
      Eliminate Health Disparities (META-Health) Study. Depression was determined by
      responses to the Beck Depression Inventory II (BDI-II). Multivariable linear
      regression models were used to adjust for demographic and metabolic risk factors.
      RESULTS: African American men had higher total BDI-II scores than white men (p =
      .03), whereas there was no difference in women. There was a significant race-sex
      depression interaction in predicting CRP levels (p = .02). White women with mild
      to severe depressive symptoms had higher levels of CRP compared with those with
      minimal to no depressive symptoms (p < .05). There were no differences in levels
      of CRP by severity of depressive symptoms in white men or African Americans of
      either sex. Higher BDI-II scores were related to higher CRP levels in white women
      after adjusting for age and level of education (beta = 0.227, p = .006). However,
      the association was eliminated after further adjustment for metabolic risk
      factors (beta = 0.077, p = .35). CONCLUSIONS: Although depressive symptoms are
      associated with inflammation, the association varies by race and sex.

PMID- 21715302
TI  - Analysis of GATA1 mutations in Down syndrome transient myeloproliferative
      disorder and myeloid leukemia.
AB  - Children with Down syndrome (DS) up to the age of 4 years are at a 150-fold
      excess risk of developing myeloid leukemia (ML-DS). Approximately 4%-5% of
      newborns with DS develop transient myeloproliferative disorder (TMD). Blast cell
      structure and immunophenotype are similar in TMD and ML-DS. A mutation in the
      hematopoietic transcription factor GATA1 is present in almost all cases. Here, we
      show that simple techniques detect GATA1 mutations in the largest series of TMD
      (n = 134; 88%) and ML-DS (n = 103; 85%) cases tested. Furthermore, no significant
      difference in the mutational spectrum between the 2 disorders was seen. Thus, the
      type of GATA1 sequence mutation is not a reliable tool and is not prognostic of
      which patients with TMD are probable to develop ML-DS.

PMID- 21715303
TI  - An RNAi-based system for loss-of-function analysis identifies Raf1 as a crucial
      mediator of BCR-ABL-driven leukemogenesis.
AB  - Genetic loss-of-function studies in murine tumor models have been essential in
      the analysis of downstream mediators of oncogenic transformation. Unfortunately,
      these studies are frequently limited by the availability of genetically modified
      mouse strains. Here we describe a versatile method allowing the efficient
      expression of an oncogene and simultaneous knockdown of targets of interest (TOI)
      from a single retroviral vector. Both oncogene and TOI-specific miR30-based shRNA
      are under the control of the strong viral long terminal repeat promoter,
      resulting in a single shared RNA transcript. Using this vector in a murine
      syngeneic BM transplantation model for BCR-ABL-induced chronic myeloid leukemia,
      we find that oncogene expression and target knockdown in primary hematopoietic
      cells with this vector is efficient both in vitro and in vivo, and demonstrate
      that Raf1, but not BRAF, modulates BCR-ABL-dependent ERK activation and
      transformation of hematopoietic cells. This expression system could facilitate
      genetic loss-of-function studies and allow the rapid validation of potential drug
      targets in a broad range of oncogene-driven murine tumor models.

PMID- 21715304
TI  - BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR
      transcription.
AB  - The oncoprotein BCR-ABL transforms myeloid progenitor cells and is responsible
      for the development of chronic myeloid leukemia (CML). In transformed cells, BCR
      ABL suppresses apoptosis as well as autophagy, a catabolic process in which
      cellular components are degraded by the lysosomal machinery. The mechanism by
      which BCR-ABL suppresses autophagy is not known. Here we report that in both
      mouse and human BCR-ABL-transformed cells, activating transcription factor 5
      (ATF5), a prosurvival factor, suppresses autophagy but does not affect apoptosis.
      We find that BCR-ABL, through PI3K/AKT/FOXO4 signaling, transcriptionally up
      regulates ATF5 expression and that ATF5, in turn, stimulates transcription of
      mammalian target of rapamycin (mTOR; also called mechanistic target of
      rapamycin), a well-established master negative-regulator of autophagy. Previous
      studies have shown that the BCR-ABL inhibitor imatinib mesylate induces both
      apoptosis and autophagy, and that the resultant autophagy modulates the
      efficiency by which imatinib kills BCR-ABL-transformed cells. We demonstrate that
      imatinib-induced autophagy is because of inhibition of the BCR
      ABL/PI3K/AKT/FOXO4/ATF5/mTOR pathway that we have identified in this study.

PMID- 21715305
TI  - Cytokine-induced osteopoietic differentiation of transplanted marrow cells.
AB  - Transplantation of whole bone marrow (BMT) leads to engraftment of both
      osteoprogenitor cells and hematopoietic cells; however, the robust osteopoietic
      chimerism seen early after BMT decreases with time. Using our established murine
      model, we demonstrate that a post-BMT regimen of either granulocyte-colony
      stimulating factor, growth hormone, parathyroid hormone, or stem cell factor each
      stimulates greater donor osteoblast chimerism at 4 months posttransplantation
      than saline-treated controls and approximates the robust osteopoietic chimerism
      seen early after BMT; however, only growth hormone led to significantly more
      donor-derived osteocytes than controls. Importantly, there were no adverse
      hematologic consequences of the different treatments. Our data demonstrate that
      these cytokines can stimulate the differentiation of transplanted donor marrow
      cells into the osteopoietic lineage after BMT. Post-BMT cytokine therapy may
      generate durable osteopoietic engraftment, which should lead to sustained
      clinical benefit and render BMT more applicable to bone disorders.

PMID- 21715306
TI  - Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand
      factor.
AB  - von Willebrand factor (VWF) is a large adhesive glycoprotein with established
      functions in hemostasis. It serves as a carrier for factor VIII and acts as a
      vascular damage sensor by attracting platelets to sites of vessel injury. VWF
      size is important for this latter function, with larger multimers being more
      hemostatically active. Functional imbalance in multimer size can variously cause
      microvascular thrombosis or bleeding. The regulation of VWF multimeric size and
      platelet-tethering function is carried out by ADAMTS13, a plasma metalloprotease
      that is constitutively active. Unusually, protease activity of ADAMTS13 is
      controlled not by natural inhibitors but by conformational changes in its
      substrate, which are induced when VWF is subject to elevated rheologic shear
      forces. This transforms VWF from a globular to an elongated protein. This
      conformational transformation unfolds the VWF A2 domain and reveals cryptic
      exosites as well as the scissile bond. To enable VWF proteolysis, ADAMTS13 makes
      multiple interactions that bring the protease to the substrate and position it to
      engage with the cleavage site as this becomes exposed by shear. This article
      reviews recent literature on the interaction between these 2 multidomain proteins
      and provides a summary model to explain proteolytic regulation of VWF by
      ADAMTS13.

PMID- 21715307
TI  - Inflammation-restraining effects of prostaglandin E2 on natural killer-dendritic
      cell (NK-DC) interaction are imprinted during DC maturation.
AB  - Among prostaglandins (PGs), PGE2 is abundantly expressed in various malignancies
      and is probably one of many factors promoting tumor growth by inhibiting tumor
      immune surveillance. In the current study, we report on a novel mechanism by
      which PGE2 inhibits in vitro natural killer-dendritic cell (NK-DC) crosstalk and
      thereby innate and adaptive immune responses via its effect on NK-DC crosstalk.
      The presence of PGE2 during IFN-gamma/membrane fraction of Klebsiella pneumoniae
      DC maturation inhibits the production of chemokines (CCL5, CCL19, and CXCL10) and
      cytokines (IL-12 and IL-18), which is cAMP-dependent and imprinted during DC
      maturation. As a consequence, these DCs fail to attract NK cells and show a
      decreased capacity to trigger NK cell IFN-gamma production, which in turn leads
      to reduced T-helper 1 polarization. In addition, the presence of PGE2 during DC
      maturation impairs DC-mediated augmentation of NK-cell cytotoxicity. Opposed to
      their inhibitory effects on peripheral blood-derived NK cells, PGE2 matured DCs
      induce IL-22 secretion of inflammation constraining NKp44(+) NK cells present in
      mucosa-associated lymphoid tissue. The inhibition of NK-DC interaction is a novel
      regulatory property of PGE2 that is of possible relevance in dampening immune
      responses in vivo.

PMID- 21715308
TI  - Adult human circulating CD34-Lin-CD45-CD133- cells can differentiate into
      hematopoietic and endothelial cells.
AB  - A precise identification of adult human hemangioblast is still lacking. To
      identify circulating precursors having the developmental potential of the
      hemangioblast, we established a new ex vivo long-term culture model supporting
      the differentiation of both hematopoietic and endothelial cell lineages. We
      identified from peripheral blood a population lacking the expression of CD34,
      lineage markers, CD45 and CD133 (CD34-Lin-CD45-CD133- cells), endowed with the
      ability to differentiate after a 6-week culture into both hematopoietic and
      endothelial lineages. The bilineage potential of CD34-Lin-CD45-CD133- cells was
      determined at the single-cell level in vitro and was confirmed by transplantation
      into NOD/SCID mice. In vivo, CD34-Lin-CD45-CD133- cells showed the ability to
      reconstitute hematopoietic tissue and to generate functional endothelial cells
      that contribute to new vessel formation during tumor angiogenesis. Molecular
      characterization of CD34-Lin-D45-CD133- cells unveiled a stem cell profile
      compatible with both hematopoietic and endothelial potentials, characterized by
      the expression of c-Kit and CXCR4 as well as EphB4, EphB2, and ephrinB2. Further
      molecular and functional characterization of CD34-Lin-CD45-CD133- cells will help
      dissect their physiologic role in blood and blood vessel maintenance and repair
      in adult life.

PMID- 21715309
TI  - Silencing of RhoA nucleotide exchange factor, ARHGEF3, reveals its unexpected
      role in iron uptake.
AB  - Genomewide association meta-analysis studies have identified > 100 independent
      genetic loci associated with blood cell indices, including volume and count of
      platelets and erythrocytes. Although several of these loci encode known
      regulators of hematopoiesis, the mechanism by which most sequence variants exert
      their effect on blood cell formation remains elusive. An example is the Rho
      guanine nucleotide exchange factor, ARHGEF3, which was previously implicated by
      genomewide association meta-analysis studies in bone cell biology. Here, we
      report on the unexpected role of ARHGEF3 in regulation of iron uptake and
      erythroid cell maturation. Although early erythroid differentiation progressed
      normally, silencing of arhgef3 in Danio rerio resulted in microcytic and
      hypochromic anemia. This was rescued by intracellular supplementation of iron,
      showing that arhgef3-depleted erythroid cells are fully capable of
      hemoglobinization. Disruption of the arhgef3 target, RhoA, also produced severe
      anemia, which was, again, corrected by iron injection. Moreover, silencing of
      ARHGEF3 in erythromyeloblastoid cells K562 showed that the uptake of transferrin
      was severely impaired. Taken together, this is the first study to provide
      evidence for ARHGEF3 being a regulator of transferrin uptake in erythroid cells,
      through activation of RHOA.

PMID- 21715310
TI  - The manipulation of miRNA-gene regulatory networks by KSHV induces endothelial
      cell motility.
AB  - miRNAs have emerged as master regulators of cancer-related events. miRNA
      dysregulation also occurs in Kaposi sarcoma (KS). Exploring the roles of KS
      associated miRNAs should help to identify novel angiogenesis and
      lymphangiogenesis pathways. In the present study, we show that Kaposi sarcoma
      associated herpesvirus (KSHV), the etiological agent of KS, induces global miRNA
      changes in lymphatic endothelial cells (LECs). Specifically, the miR-221/miR-222
      cluster is down-regulated, whereas miR-31 is up-regulated. Both latent nuclear
      antigen (LANA) and Kaposin B repress the expression of the miR-221/miR-222
      cluster, which results in an increase of endothelial cell (EC) migration. In
      contrast, miR-31 stimulates EC migration, so depletion of miR-31 in KSHV
      transformed ECs reduces cell motility. Analysis of the putative miRNA targets
      among KSHV-affected genes showed that ETS2 and ETS1 are the downstream targets of
      miR-221 and miR-222, respectively. FAT4 is one of the direct targets of miR-31.
      Overexpression of ETS1 or ETS2 alone is sufficient to induce EC migration,
      whereas a reduction in FAT4 enhances EC motility. Our results show that KSHV
      regulates multiple miRNA-mRNA networks to enhance EC motility, which eventually
      contributes to KS progression by promoting the spread of malignant KS progenitor
      cells. Targeting KSHV-regulated miRNAs or genes might allow the development of
      novel therapeutic strategies that induce angiogenesis or allow the treatment of
      pathogenic (lymph)angiogenesis.

PMID- 21715311
TI  - Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia.
AB  - Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated
      with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein,
      suggesting a survival advantage for ALL cells. In the present study, we report
      that inhibition of survivin in patient-derived ALL can eradicate leukemia.
      Targeting survivin with shRNA in combination with chemotherapy resulted in no
      detectable minimal residual disease in a xenograft model of primary ALL.
      Similarly, pharmacologic knock-down of survivin using EZN-3042, a novel locked
      nucleic acid antisense oligonucleotide, in combination with chemotherapy
      eliminated drug-resistant ALL cells. These findings show the importance of
      survivin expression in drug resistance and demonstrate that survivin inhibition
      may represent a powerful approach to overcoming drug resistance and preventing
      relapse in patients with ALL.

PMID- 21715312
TI  - AF1q/MLLT11 regulates the emergence of human prothymocytes through cooperative
      interaction with the Notch signaling pathway.
AB  - The mechanisms regulating the emergence of BM prothymocytes remain poorly
      characterized. Genome-wide transcriptome analyses looking for genes expressed in
      human prothymocytes led to the identification of AF1q/MLLT11 as a candidate gene
      conceivably involved in this process. Analysis of AF1q protein subcellular
      localization and intracellular trafficking showed that despite pronounced
      karyophily, it was subjected to constitutive nuclear export followed by ubiquitin
      mediated degradation in the centrosomal area. Using in vitro assays based on
      either forced expression or shRNA-mediated silencing of AF1q, we provide evidence
      that the protein promotes T- over B-cell differentiation in multipotent
      hematopoietic progenitors. At the molecular level, AF1q confers to multipotent
      progenitors an increased susceptibility to Delta-like/Notch-mediated signaling.
      Consistent with these findings, enforced AF1q expression in humanized mice
      fosters the emergence of BM CD34(+)CD7(+) prothymocytes, enhances subsequent
      thymus colonization, and accelerates intrathymic T-cell development. In contrast,
      AF1q silencing provokes a global shift of BM lymphopoiesis toward the B-cell
      lineage, hinders prothymocyte development, inhibits thymus colonization, and
      leads to intrathymic accumulation of B cells. Our results indicate that AF1q
      cooperates with the Notch signaling pathway to foster the emergence of BM
      prothymocytes and drive subsequent intrathymic specification toward the T-cell
      lineage.

PMID- 21715313
TI  - Reduced-intensity conditioning therapy with busulfan, fludarabine, and
      antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation
      in acute leukemia and myelodysplastic syndrome.
AB  - Any role for reduced-intensity conditioning (RIC) before hematopoietic cell
      transplantation (HCT) from a human leukocyte antigen (HLA)-haploidentical donor
      remains to be defined. We therefore assessed 83 patients (age, 16-70 years): 68
      with acute leukemia (including 34 in remission and 34 with refractory disease)
      and 15 patients with myelodysplastic syndrome, in HCT trials using RIC with
      busulfan, fludarabine, and antithymocyte globulin. The HLA-haploidentical donors,
      offspring (n = 38), mothers (n = 24), or siblings (n = 21) of patients, underwent
      leukapheresis after receiving granulocyte colony-stimulating factor, and donated
      cells were transplanted without further manipulation. Cyclosporine and
      methotrexate were given for GVHD prophylaxis. The cumulative incidences of
      neutrophil engraftment, grade 2 to 4 acute GVHD, chronic GVHD, and
      transplantation-related mortality after HCT, were 92%, 20%, 34%, and 18%,
      respectively. After a median follow-up time of 26.6 months (range, 16.8-78.8
      months), the event-free and overall survival rates were 56% and 45%,
      respectively, for patients with acute leukemia in remission; 9% and 9%,
      respectively, for patients with refractory acute leukemia; and 53% and 53%,
      respectively, for patients with myelodysplastic syndrome. HCT from an HLA
      haploidentical family member resulted in favorable outcomes when RIC containing
      antithymocyte globulin was performed. This study is registered at
      www.clinicaltrials.gov as #NCT00521430 and #NCT00732316.

PMID- 21715314
TI  - Foxp3+ regulatory T cells exert asymmetric control over murine helper responses
      by inducing Th2 cell apoptosis.
AB  - Foxp3(+) regulatory T cells play a pivotal role in maintaining self-tolerance and
      immune homeostasis. In the absence of regulatory T cells, generalized immune
      activation and multiorgan T cell-driven pathology occurs. Although the phenomenon
      of immunologic control by Foxp3(+) regulatory T cells is well recognized, the
      comparative effect over different arms of the immune system has not been
      thoroughly investigated. Here, we generated a cohort of mice with a continuum of
      regulatory T-cell frequencies ranging from physiologic levels to complete
      deficiency. This titration of regulatory T-cell depletion was used to determine
      how different effector subsets are controlled. We found that in vivo Foxp3(+)
      regulatory T-cell frequency had a proportionate relationship with generalized T
      cell activation and Th1 magnitude, but it had a surprising disproportionate
      relationship with Th2 magnitude. The asymmetric regulation was associated with
      efficient suppression of Th2 cells through additional regulations on the
      apoptosis rate in Th2 cells and not Th1 cells and could be replicated by CTLA4-Ig
      or anti-IL-2 Ab. These results indicate that the Th2 arm of the immune system is
      under tighter control by regulatory T cells than the Th1 arm, suggesting that Th2
      driven diseases may be more responsive to regulatory T-cell manipulation.

PMID- 21715315
TI  - Lack of the T cell-specific alternative p38 activation pathway reduces
      autoimmunity and inflammation.
AB  - Stimulation via the T-cell receptor (TCR) activates p38alpha and p38beta by
      phosphorylation of p38 Tyr-323 (p38(Y323)). Here we characterize knockin mice in
      which p38alpha and/or beta Tyr-323 has been replaced with Phe. We find that
      p38alpha accounts for two-thirds and p38beta the remainder of TCR-induced p38
      activation. T cells from double knockin mice (p38alphabeta(Y323F)) had defects in
      TCR-mediated proliferation and Th1 and Th17 skewing, the former corresponding
      with an inability to sustain T-bet expression. Introduction of p38alpha(Y323F)
      into Gadd45alpha-deficient mice, in which the alternative p38 pathway is
      constitutively active, reversed T-cell hyperproliferation and autoimmunity.
      Furthermore, p38alphabeta(Y323F) mice had delayed onset and reduced severity of
      the inflammatory autoimmune diseases collagen-induced arthritis and experimental
      autoimmune encephalomyelitis. Thus, T cell-specific alternative activation of p38
      is an important pathway in T-cell proliferation, Th skewing, and inflammatory
      autoimmunity, and may be an attractive tissue-specific target for intervention in
      these processes.

PMID- 21715316
TI  - acDCs enhance human antigen-specific T-cell responses.
AB  - Detection of human Ag-specific T cells is limited by sensitivity and blood
      requirements. As dendritic cells (DCs) can potently stimulate T cells, we
      hypothesized that their induction in PBMCs in situ could link Ag processing and
      presentation to Ag-specific T-cell activation. To this end, unfractionated PBMCs
      (fresh or frozen) or whole blood were incubated for 48 hours with protein or
      peptide Ag together with different DC-activating agents to rapidly and
      sequentially induce, pulse, and mature DCs. DC activation was therefore lined up
      with Ag recognition by neighboring T cells, thus telescoping the sequential steps
      of T-cell activation. Efficient processing of protein Ags made prior knowledge of
      epitopes and HLA restrictions dispensable. While reducing stimulation time,
      manipulation and blood requirements, in situ DC induction specifically amplified
      Ag-specific T-cell responses (cytokine secretion, proliferation, CD137/CD154 up
      regulation, and binding of peptide-HLA multimers). IL-1beta, although released by
      DCs, was also secreted in an Ag-specific fashion, thus providing an indirect
      biomarker of T-cell responses. These accelerated cocultured DC (acDC) assays
      offered a sensitive means with which to evaluate T-cell responses to viral and
      melanoma Ag vaccination, and may therefore find application for immune monitoring
      in viral, tumor, autoimmune, and transplantation settings.

PMID- 21715317
TI  - Differential and tumor-specific expression of CD160 in B-cell malignancies.
AB  - CD160 is a human natural killer (NK)-cell-activating receptor that is also
      expressed on T-cell subsets. In the present study, we examined 811 consecutive
      cases of B-cell lymphoproliferative disorders (B-LPDs), and demonstrated CD160
      expression in 98% (590 of 600) of chronic lymphocytic leukemia (CLL) cases, 100%
      (32 of 32) of hairy cell leukemia (HCL) cases, 15% (5 of 34) of mantle cell
      lymphoma (MCL) in the leukemic phase, and 16% (23 of 145) of other B-LPD cases.
      CD160 transcript and protein were absent in the normal B-cell hierarchy, from
      stem cells, B-cell precursors, maturing B cells in the germinal center, and
      circulating B cells, including CD5(+)CD19(+) B1 cells in umbilical cord. CD160
      positivity was significantly higher in CLL and HCL in terms of percentage (65.9%
      and 67.8%, respectively, P < .0001) and median fluorescence intensity (552 and
      857, respectively, P < .0001) compared with all other B-LPD cases. Lymph node CLL
      samples were also CD160(+). Using the disease-specific expression of CD5, CD23,
      and CD160, a score of 3 characterized CLL (diagnostic odds ratio, 1430); a score
      of 0 excluded CLL, MCL, and HCL; and the CD23/CD5 ratio differentiated CLL from
      leukemic CD23(+) MCL. In the B-cell lineage, CD160 is a tumor-specific antigen
      known to mediate cellular activation signals in CLL, and is a novel target for
      therapeutic manipulation and monitoring of minimal residual disease.

PMID- 21715318
TI  - High single-drug activity of nelarabine in relapsed T-lymphoblastic
      leukemia/lymphoma offers curative option with subsequent stem cell
      transplantation.
AB  - Nelarabine, a purine analog with T-cell specific action, has been approved for
      relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL). This
      is a report of a single-arm phase 2 study conducted in adults (18-81 years of
      age) with relapsed/refractory T-ALL/LBL. After 1 or 2 cycles, 45 of 126 evaluable
      patients (36%) achieved complete remission (CR), 12 partial remission (10%), and
      66 (52%) were refractory. One treatment-related death was observed, and 2
      patients were withdrawn before evaluation. A total of 80% of the CR patients were
      transferred to stem cell transplantation (SCT). Overall survival was 24% at 1
      year (11% at 6 years). After subsequent SCT in CR, survival was 31% and relapse
      free survival 37% at 3 years. Transplantation-related mortality was 11%.
      Neurologic toxicities of grade I-IV/grade III-IV were observed in 13%/4% of the
      cycles and 16%/7% of the patients. This largest study so far with nelarabine in
      adults showed impressive single-drug activity in relapsed T-ALL/T-LBL. The drug
      was well tolerated, even in heavily pretreated patients. A high proportion of CR
      patients were transferred to SCT with low mortality but a high relapse rate.
      Exploration of nelarabine in earlier stages of relapse (eg, increasing minimal
      residual disease), in front-line therapy, and in combination is warranted.

PMID- 21715319
TI  - Conformational transitions in the membrane scaffold protein of phospholipid
      bilayer nanodiscs.
AB  - Phospholipid bilayer nanodiscs are model membrane systems that provide an
      environment where membrane proteins are highly stable and monodisperse without
      the use of detergents or liposomes. Nanodiscs consist of a discoidal phospholipid
      bilayer encircled by two copies of an amphipathic alpha helical membrane scaffold
      protein, which is modeled from apolipoprotein A-1. Hydrogen exchange mass
      spectrometry was used to probe the structure and dynamics of the scaffold protein
      in the presence and absence of lipid. On nanodisc self-assembly, the entire
      scaffold protein gained significant protection from exchange, consistent with a
      large, protein-wide, structural rearrangement. This protection was short-lived
      and the scaffold protein was highly deuterated within 2 h. Several regions of the
      scaffold protein, in both the lipid-free and lipid-associated states, displayed
      EX1 unfolding kinetics. The rapid deuteration of the scaffold protein and the
      presence of correlated unfolding events both indicate that nanodiscs are dynamic
      rather than rigid bodies in solution. This work provides a catalog of the
      expected scaffold protein peptic peptides in a nanodisc-hydrogen exchange mass
      spectrometry experiment and their deuterium uptake signatures, data that can be
      used as a benchmark to verify correct assembly and nanodisc structure. Such
      reference data will be useful control data for all hydrogen exchange mass
      spectrometry experiments involving nanodiscs in which transmembrane or lipid
      associated proteins are the primary molecule(s) of interest.

PMID- 21715320
TI  - Enhancing the identification of phosphopeptides from putative basophilic kinase
      substrates using Ti (IV) based IMAC enrichment.
AB  - Metal and metal oxide chelating-based phosphopeptide enrichment technologies
      provide powerful tools for the in-depth profiling of phosphoproteomes. One
      weakness inherent to current enrichment strategies is poor binding of
      phosphopeptides containing multiple basic residues. The problem is exacerbated
      when strong cation exchange (SCX) is used for pre-fractionation, as under low pH
      SCX conditions phosphorylated peptides with multiple basic residues elute with
      the bulk of the tryptic digest and therefore require more stringent enrichment.
      Here, we report a systematic evaluation of the characteristics of a novel
      phosphopeptide enrichment approach based on a combination of low pH SCX and
      Ti(4+)-immobilized metal ion affinity chromatography (IMAC) comparing it one-to
      one with the well established low pH SCX-TiO(2) enrichment method. We also
      examined the effect of 1,1,1,3,3,3-hexafluoroisopropanol (HFP), trifluoroacetic
      acid (TFA), or 2,5-dihydroxybenzoic acid (DHB) in the loading buffer, as it has
      been hypothesized that high levels of TFA and the perfluorinated solvent HFP
      improve the enrichment of phosphopeptides containing multiple basic residues. We
      found that Ti(4+)-IMAC in combination with TFA in the loading buffer,
      outperformed all other methods tested, enabling the identification of around 5000
      unique phosphopeptides containing multiple basic residues from 400 MUg of a HeLa
      cell lysate digest. In comparison, ~ 2000 unique phosphopeptides could be
      identified by Ti(4+)-IMAC with HFP and close to 3000 by TiO(2). We confirmed, by
      motif analysis, the basic phosphopeptides enrich the number of putative
      basophilic kinases substrates. In addition, we performed an experiment using the
      SCX/Ti(4+)-IMAC methodology alongside the use of collision-induced dissociation
      (CID), higher energy collision induced dissociation (HCD) and electron transfer
      dissociation with supplementary activation (ETD) on considerably more complex
      sample, consisting of a total of 400 MUg of triple dimethyl labeled MCF-7 digest.
      This analysis led to the identification of over 9,000 unique phosphorylation
      sites. The use of three peptide activation methods confirmed that ETD is best
      capable of sequencing multiply charged peptides. Collectively, our data show that
      the combination of SCX and Ti(4+)-IMAC is particularly advantageous for
      phosphopeptides with multiple basic residues.

PMID- 21715321
TI  - A study of the spatial protein organization of the postsynaptic density isolated
      from porcine cerebral cortex and cerebellum.
AB  - Postsynaptic density (PSD) is a protein supramolecule lying underneath the
      postsynaptic membrane of excitatory synapses and has been implicated to play
      important roles in synaptic structure and function in mammalian central nervous
      system. Here, PSDs were isolated from two distinct regions of porcine brain,
      cerebral cortex and cerebellum. SDS-PAGE and Western blotting analyses indicated
      that cerebral and cerebellar PSDs consisted of a similar set of proteins with
      noticeable differences in the abundance of various proteins between these
      samples. Subsequently, protein localization in these PSDs was analyzed by using
      the Nano-Depth-Tagging method. This method involved the use of three synthetic
      reagents, as agarose beads whose surface was covalently linked with a
      fluorescent, photoactivable, and cleavable chemical crosslinker by spacers of
      varied lengths. After its application was verified by using a synthetic complex
      consisting of four layers of different proteins, the Nano-Depth-Tagging method
      was used here to yield information concerning the depth distribution of various
      proteins in the PSD. The results indicated that in both cerebral and cerebellar
      PSDs, glutamate receptors, actin, and actin binding proteins resided in the
      peripheral regions within ~ 10 nm deep from the surface and that scaffold
      proteins, tubulin subunits, microtubule-binding proteins, and membrane
      cytoskeleton proteins found in mammalian erythrocytes resided in the interiors
      deeper than 10 nm from the surface in the PSD. Finally, by using the
      immunoabsorption method, binding partner proteins of two proteins residing in the
      interiors, PSD-95 and alpha-tubulin, and those of two proteins residing in the
      peripheral regions, elongation factor-1alpha and calcium, calmodulin-dependent
      protein kinase II alpha subunit, of cerebral and cerebellar PSDs were identified.
      Overall, the results indicate a striking similarity in protein organization
      between the PSDs isolated from porcine cerebral cortex and cerebellum. A model of
      the molecular structure of the PSD has also been proposed here.

PMID- 21715322
TI  - Galectin-3 protein modulates cell surface expression and activation of vascular
      endothelial growth factor receptor 2 in human endothelial cells.
AB  - Angiogenesis is heavily influenced by VEGF-A and its family of receptors,
      particularly VEGF receptor 2 (VEGF-R2). Like most cell surface proteins, VEGF-R2
      is glycosylated, although the function of VEGF-R2 with respect to its
      glycosylation pattern is poorly characterized. Galectin-3, a glycan binding
      protein, interacts with the EGF and TGFbeta receptors, retaining them on the
      plasma membrane and altering their signal transduction. Because VEGF-R2 is
      glycosylated and both galectin-3 and VEGF-R2 are involved with angiogenesis, we
      hypothesized that galectin-3 binds VEGF-R2 and modulates its signal transduction
      as well. Employing a Western blot analysis approach, we found that galectin-3
      induces phosphorylation of VEGF-R2 in endothelial cells. Knockdown of galectin-3
      and Mgat5, an enzyme that synthesizes high-affinity glycan ligands of galectin-3,
      reduced VEGF-A mediated angiogenesis in vitro. A direct interaction on the plasma
      membrane was detected between galectin-3 and VEGF-R2, and this interaction was
      dependent on the expression of Mgat5. Using immunofluorescence and cell surface
      labeling, we found an increase in the level of internalized VEGF-R2 in both Mgat5
      and galectin-3 knockdown cells, suggesting that galectin-3 retains the receptor
      on the plasma membrane. Finally, we observed reduced suture-induced
      neovascularization in the corneas of Gal3(-/-) and Mgat5(-/-) mice. These
      findings are consistent with the hypothesis that, like its role with the EGF and
      TGFbeta receptors, galectin-3 contributes to the plasma membrane retention and
      proangiogenic function of VEGF-R2.

PMID- 21715323
TI  - Mitochondrial-targeted Signal transducer and activator of transcription 3 (STAT3)
      protects against ischemia-induced changes in the electron transport chain and the
      generation of reactive oxygen species.
AB  - Expression of the STAT3 transcription factor in the heart is cardioprotective and
      decreases the levels of reactive oxygen species. Recent studies indicate that a
      pool of STAT3 resides in the mitochondria where it is necessary for the maximal
      activity of complexes I and II of the electron transport chain. However, it has
      not been explored whether mitochondrial STAT3 modulates cardiac function under
      conditions of stress. Transgenic mice with cardiomyocyte-specific overexpression
      of mitochondria-targeted STAT3 with a mutation in the DNA-binding domain (MLS
      STAT3E) were generated. We evaluated the role of mitochondrial STAT3 in the
      preservation of mitochondrial function during ischemia. Under conditions of
      ischemia heart mitochondria expressing MLS-STAT3E exhibited modest decreases in
      basal activities of complexes I and II of the electron transport chain. In
      contrast to WT hearts, complex I-dependent respiratory rates were protected
      against ischemic damage in MLS-STAT3E hearts. MLS-STAT3E prevented the release of
      cytochrome c into the cytosol during ischemia. In contrast to WT mitochondria,
      ischemia did not augment reactive oxygen species production in MLS-STAT3E
      mitochondria likely due to an MLS-STAT3E-mediated partial blockade of electron
      transport through complex I. Given the caveat of STAT3 overexpression, these
      results suggest a novel protective mechanism mediated by mitochondrial STAT3 that
      is independent of its canonical activity as a nuclear transcription factor.

PMID- 21715324
TI  - Crystal structure of the ubiquitin-associated (UBA) domain of p62 and its
      interaction with ubiquitin.
AB  - p62/SQSTM1/A170 is a multimodular protein that is found in ubiquitin-positive
      inclusions associated with neurodegenerative diseases. Recent findings indicate
      that p62 mediates the interaction between ubiquitinated proteins and
      autophagosomes, leading these proteins to be degraded via the autophagy-lysosomal
      pathway. This ubiquitin-mediated selective autophagy is thought to begin with
      recognition of the ubiquitinated proteins by the C-terminal ubiquitin-associated
      (UBA) domain of p62. We present here the crystal structure of the UBA domain of
      mouse p62 and the solution structure of its ubiquitin-bound form. The p62 UBA
      domain adopts a novel dimeric structure in crystals, which is distinctive from
      those of other UBA domains. NMR analyses reveal that in solution the domain
      exists in equilibrium between the dimer and monomer forms, and binding ubiquitin
      shifts the equilibrium toward the monomer to form a 1:1 complex between the UBA
      domain and ubiquitin. The dimer-to-monomer transition is associated with a
      structural change of the very C-terminal end of the p62 UBA domain, although the
      UBA fold itself is essentially maintained. Our data illustrate that dimerization
      and ubiquitin binding of the p62 UBA domain are incompatible with each other.
      These observations reveal an autoinhibitory mechanism in the p62 UBA domain and
      suggest that autoinhibition plays a role in the function of p62.

PMID- 21715325
TI  - Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a
      response inhibited by monomeric glucocorticoid receptor.
AB  - Increased vitamin A (retinol) intake has been suggested to increase bone
      fragility. In the present study, we investigated effects of retinoids on bone
      resorption in cultured neonatal mouse calvarial bones and their interaction with
      glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde,
      and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The
      resorptive effect of ATRA was characterized by mRNA expression of genes
      associated with osteoclast differentiation, enhanced osteoclast number, and bone
      matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA,
      release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA
      expression of genes associated with bone formation was decreased by ATRA. All
      retinoid acid receptors (RARalpha/beta/gamma) were expressed in calvarial bones.
      Agonists with affinity to all receptor subtypes or specifically to RARalpha
      enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists
      with affinity to RARbeta/gamma or RARgamma had no effects. Stimulation of Rankl
      mRNA by ATRA was competitively inhibited by the RARalpha antagonist GR110.
      Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on
      (45)Ca release and Rankl mRNA and protein expression. This inhibitory effect was
      reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl
      mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with
      a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA
      enhances periosteal bone resorption by increasing the RANKL/OPG ratio via
      RARalpha receptors, a response that can be inhibited by monomeric GR.

PMID- 21715326
TI  - Phage display of tissue inhibitor of metalloproteinases-2 (TIMP-2):
      identification of selective inhibitors of collagenase-1 (metalloproteinase 1 (MMP
      1)).
AB  - Tissue inhibitor of metalloproteinases-2 (TIMP-2) is a broad spectrum inhibitor
      of the matrix metalloproteinases (MMPs), which function in extracellular matrix
      catabolism. Here, phage display was used to identify variants of human TIMP-2
      that are selective inhibitors of human MMP-1, a collagenase whose unregulated
      action is linked to cancer, arthritis, and fibrosis. Using hard randomization of
      residues 2, 4, 5, and 6 (L1) and soft randomization of residues 34-40 (L2) and 67
      70 (L3), a library was generated containing 2 * 10(10) variants of TIMP-2. Five
      clones were isolated after five rounds of selection with MMP-1, using MMP-3 as a
      competitor. The enriched phages selectively bound MMP-1 relative to MMP-3 and
      contained mutations only in L1. The most selective variant (TM8) was used to
      generate a second library in which residues Cys(1)-Gln(9) were soft-randomized.
      Four additional clones, selected from this library, showed a similar affinity for
      MMP-1 as wild-type TIMP-2 but reduced affinity for MMP-3. Variants of the N
      terminal domain of TIMP-2 (N-TIMP-2) with the sequences of the most selective
      clones were expressed and characterized for inhibitory activity against eight
      MMPs. All were effective inhibitors of MMP-1 with nanomolar K(i) values, but TM8,
      containing Ser(2) to Asp and Ser(4) to Ala substitutions, was the most selective
      having a nanomolar K(i) value for MMP-1 but no detectable inhibitory activity
      toward MMP-3 and MMP-14 up to 10 MUM. This study suggests that phage display and
      selection with other MMPs may be an effective method for discovering tissue
      inhibitor of metalloproteinase variants that discriminate between specified MMPs
      as targets.

PMID- 21715327
TI  - Baculovirus envelope protein ODV-E66 is a novel chondroitinase with distinct
      substrate specificity.
AB  - Chondroitin sulfate is a linear polysaccharide of alternating D-glucuronic acid
      and N-acetyl-D-galactosamine residues with sulfate groups at various positions of
      the sugars. It interacts with and regulates cytokine and growth factor signal
      transduction, thus influencing development, organ morphogenesis, inflammation,
      and infection. We found chondroitinase activity in medium conditioned by
      baculovirus-infected insect cells and identified a novel chondroitinase. Sequence
      analysis revealed that the enzyme was a truncated form of occlusion-derived virus
      envelope protein 66 (ODV-E66) of Autographa californica nucleopolyhedrovirus. The
      enzyme was a novel chondroitin lyase with distinct substrate specificity. The
      enzyme was active over a wide range of pH (pH 4-9) and temperature (30-60 
      degrees C) and was unaffected by divalent metal ions. The ODV-E66 truncated
      protein digested chondroitin most efficiently followed by chondroitin 6-sulfate.
      It degraded hyaluronan to a minimal extent but did not degrade dermatan sulfate,
      heparin, and N-acetylheparosan. Further analysis using chemo-enzymatically
      synthesized substrates revealed that the enzyme specifically acted on glucuronate
      residues in non-sulfated and chondroitin 6-sulfate structures but not in
      chondroitin 4-sulfate structures. These results suggest that this chondroitinase
      is useful for detailed structural and compositional analysis of chondroitin
      sulfate, preparation of specific chondroitin oligosaccharides, and study of
      baculovirus infection mechanism.

PMID- 21715328
TI  - Leukotrienes target F-actin/cofilin-1 to enhance alveolar macrophage anti-fungal
      activity.
AB  - Candida albicans is the most common opportunistic fungal pathogen and causes
      local and systemic disease in immunocompromised patients. Alveolar macrophages
      (AMs) are pivotal for the clearance of C. albicans from the lung. Activated AMs
      secrete 5-lipoxygenase-derived leukotrienes (LTs), which in turn enhance
      phagocytosis and microbicidal activity against a diverse array of pathogens. Our
      aim was to investigate the role of LTB(4) and LTD(4) in AM antimicrobial
      functions against C. albicans and the signaling pathways involved. Pharmacologic
      and genetic inhibition of LT biosynthesis as well as receptor antagonism reduced
      phagocytosis of C. albicans when compared with untreated or WT controls.
      Conversely, exogenous LTs of both classes augmented base-line C. albicans
      phagocytosis by AMs. Although LTB(4) enhanced mainly mannose receptor-dependent
      fungal ingestion, LTD(4) enhanced mainly dectin-1 receptor-mediated phagocytosis.
      LT enhancement of yeast ingestion was dependent on protein kinase C-delta
      (PKCdelta) and PI3K but not PKCalpha and MAPK activation. Both LTs reduced
      activation of cofilin-1, whereas they enhanced total cellular F-actin; however,
      LTB(4) accomplished this through the activation of LIM kinases (LIMKs) 1 and 2,
      whereas LTD(4) did so exclusively via LIMK-2. Finally, both exogenous LTB(4) and
      LTD(4) enhanced AM fungicidal activity in an NADPH oxidase-dependent manner. Our
      data identify LTB(4) and LTD(4) as key mediators of innate immunity against C.
      albicans, which act by both distinct and conserved signaling mechanisms to
      enhance multiple antimicrobial functions of AMs.

PMID- 21715329
TI  - Crystal structure of the E2 domain of amyloid precursor protein-like protein 1 in
      complex with sucrose octasulfate.
AB  - Missense mutations in the amyloid precursor protein (APP) gene can cause familial
      Alzheimer disease. It is thought that APP and APP-like proteins (APLPs) may play
      a role in adhesion and signal transduction because their ectodomains interact
      with components of the extracellular matrix. Heparin binding induces dimerization
      of APP and APLPs. To help explain how these proteins interact with heparin, we
      have determined the crystal structure of the E2 domain of APLP1 in complex with
      sucrose octasulfate (SOS). A total of three SOS molecules are bound to the E2
      dimer. Two SOSs are bound inside a narrow intersubdomain groove, and the third
      SOS is bound near the two-fold axis of the protein. Mutational analyses show that
      most residues interacting with SOS also contribute to heparin binding, although
      in varying degrees; a deep pocket, defined by His-376, Lys-422, and Arg-429, and
      an interfacial site between Lys-314 and its symmetry mate are most important in
      the binding of the negatively charged polysaccharide. Comparison with a lower
      resolution APP structure shows that all key heparin binding residues are
      conserved and identically positioned, suggesting that APLP1 and APP may bind
      heparin similarly. In transfected HEK-293 cells, mutating residues responsible
      for heparin binding causes little change in the proteolysis of APP by the
      secretases. However, mutating a pair of conserved basic residues (equivalent to
      Arg-414 and Arg-415 of APLP1) immediately adjacent to the heparin binding site
      affects both the maturation and the processing of APP.

PMID- 21715330
TI  - Incomplete folding upon binding mediates Cdk4/cyclin D complex activation by
      tyrosine phosphorylation of inhibitor p27 protein.
AB  - p27(Kip1) (p27), an intrinsically disordered protein, regulates the various
      Cdk/cyclin complexes that control cell cycle progression. The kinase inhibitory
      domain of p27 contains a cyclin-binding subdomain (D1), a Cdk-binding subdomain
      (D2), and a linker helix subdomain that connects D1 and D2. Here, we report that,
      despite extensive sequence conservation between Cdk4/cyclin D1 (hereafter
      Cdk4/cyclin D) and Cdk2/cyclin A, the thermodynamic details describing how the
      individual p27 subdomains contribute to equally high affinity binding to these
      two Cdk/cyclin complexes are strikingly different. Differences in
      enthalpy/entropy compensation revealed that the D2 subdomain of p27 folds
      incompletely when binding Cdk4/cyclin D versus Cdk2/cyclin A. Incomplete binding
      induced folding exposes tyrosine 88 of p27 for phosphorylation by the nonreceptor
      tyrosine kinase Abl. Importantly, tyrosine phosphorylation (of p27) relieves Cdk
      inhibition by p27, enabling cell cycle entry. Furthermore, the interaction
      between a conserved hydrophobic patch on cyclin D and subdomain D1 is much weaker
      than that with cyclin A; consequently, a construct containing subdomains D1 and
      LH (p27-D1LH) does not inhibit substrate binding to Cdk4/cyclin D as it does to
      Cdk2/cyclin A. Our results provide a mechanism by which Cdk4 (within the
      p27/Cdk4/cyclin D complex) is poised to be activated by extrinsic mitogenic
      signals that impinge upon p27 at the earliest stage of cell division. More
      broadly, our results further illustrate the regulatory versatility of
      intrinsically disordered proteins.

PMID- 21715331
TI  - Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its
      phosphorylation at serine 10 and contributes to cell motility.
AB  - HIPK2 is a serine/threonine kinase that acts as a coregulator of an increasing
      number of factors involved in cell survival and proliferation during development
      and in response to different types of stress. Here we report on a novel target of
      HIPK2, the cyclin-dependent kinase inhibitor p27(kip1). HIPK2 phosphorylates
      p27(kip1) in vitro and in vivo at serine 10, an event that accounts for 80% of
      the total p27(kip1) phosphorylation and plays a crucial role in the stability of
      the protein. Indeed, HIPK2 depletion by transient or stable RNA interference in
      tumor cells of different origin was consistently associated with strong reduction
      of p27(kip1) phosphorylation at serine 10 and of p27(kip1) stability. An initial
      evaluation of the functional relevance of this HIPK2-mediated regulation of
      p27(kip1) revealed a contribution to cell motility, rather than to cell
      proliferation, but only in cells that do not express wild-type p53.

PMID- 21715332
TI  - Identification of arrestin-3-specific residues necessary for JNK3 kinase
      activation.
AB  - Arrestins bind active phosphorylated G protein-coupled receptors, blocking G
      protein activation and channeling the signaling to G protein-independent
      pathways. Free arrestin-3 and receptor-bound arrestin-3 scaffold the ASK1-MKK4
      JNK3 module, promoting JNK3 phosphorylation, whereas highly homologous arrestin-2
      does not. Here, we used arrestin-2/3 chimeras and mutants to identify key
      residues of arrestin-3 responsible for its ability to facilitate JNK3 activation.
      Our data demonstrate that both arrestin domains are involved in JNK3 activation,
      with the C-terminal domain being more important than the N-terminal domain. We
      found that Val-343 is the key contributor to this function, whereas Leu-278, Ser
      280, His-350, Asp-351, His-352, and Ile-353 play supporting roles. We also show
      that the arrestin-3-specific difference in the arrangement of the beta-strands in
      the C-terminal domain that underlies its lower selectivity for active
      phosphoreceptors does not play an appreciable role in its ability to enhance JNK3
      activation. Importantly, the strength of the binding of ASK1 or JNK3, as revealed
      by the efficiency of co-immunoprecipitation, does not correlate with the ability
      of arrestin proteins to promote ASK1-dependent JNK3 phosphorylation. Thus,
      multiple residues on the non-receptor-binding side of arrestin-3 are crucial for
      JNK3 activation, and this function and the receptor-binding characteristics of
      arrestin can be manipulated independently by targeted mutagenesis.

PMID- 21715333
TI  - T-LAK cell-originated protein kinase (TOPK) phosphorylation of MKP1 protein
      prevents solar ultraviolet light-induced inflammation through inhibition of the
      p38 protein signaling pathway.
AB  - Solar UV radiation is a major environmental factor that causes DNA damage,
      inflammation, and even skin cancer. T-LAK cell-originated protein kinase (TOPK)
      is expressed widely in both normal and cancer cells and functions to inhibit
      apoptosis and promote carcinogenesis. However, its function in inflammation is
      not known. The p38 MAPK signaling pathway plays an important role in solar UV
      light-induced inflammation. In this study, we found that TOPK negatively
      regulated the activity of p38alpha by phosphorylating the p38alpha-specific
      phosphatase MKP1 and enhancing the stability of MKP1. Notably, the absence of
      TOPK in mice resulted in a striking increase in skin inflammation. Therefore, we
      conclude that TOPK has a protective function in solar UV light-induced
      inflammation.

PMID- 21715334
TI  - Active site inhibitors protect protein kinase C from dephosphorylation and
      stabilize its mature form.
AB  - Conformational changes acutely control protein kinase C (PKC). We have previously
      shown that the autoinhibitory pseudosubstrate must be removed from the active
      site in order for 1) PKC to be phosphorylated by its upstream kinase
      phosphoinositide-dependent kinase 1 (PDK-1), 2) the mature enzyme to bind and
      phosphorylate substrates, and 3) the mature enzyme to be dephosphorylated by
      phosphatases. Here we show an additional level of conformational control; binding
      of active site inhibitors locks PKC in a conformation in which the priming
      phosphorylation sites are resistant to dephosphorylation. Using homogeneously
      pure PKC, we show that the active site inhibitor Go 6983 prevents the
      dephosphorylation by pure protein phosphatase 1 (PP1) or the hydrophobic motif
      phosphatase, pleckstrin homology domain leucine-rich repeat protein phosphatase
      (PHLPP). Consistent with results using pure proteins, treatment of cells with the
      competitive inhibitors Go 6983 or bisindolylmaleimide I, but not the
      uncompetitive inhibitor bisindolylmaleimide IV, prevents the dephosphorylation
      and down-regulation of PKC induced by phorbol esters. Pulse-chase analyses reveal
      that active site inhibitors do not affect the net rate of priming
      phosphorylations of PKC; rather, they inhibit the dephosphorylation triggered by
      phorbol esters. These data provide a molecular explanation for the recent studies
      showing that active site inhibitors stabilize the phosphorylation state of
      protein kinases B/Akt and C.

PMID- 21715335
TI  - Nrk, an X-linked protein kinase in the germinal center kinase family, is required
      for placental development and fetoplacental induction of labor.
AB  - The complete mechanism of labor induction in eutherian mammals remains unclear.
      Although important roles for the fetus and placenta in triggering labor have been
      proposed, no gene has been shown to be required in the fetus/placenta for labor
      induction. Here we show that Nrk, an X-linked gene encoding a Ser/Thr kinase of
      the germinal center kinase family, is essential in the fetus/placenta for labor
      in mice. Nrk was specifically expressed in the spongiotrophoblast layer, a fetus
      derived region of the placenta, and Nrk disruption caused dysregulated overgrowth
      of the layer. Due to preferential inactivation of the paternally derived X
      chromosome in placenta, Nrk heterozygous mutant placentas exhibited a similar
      defect to that in Nrk-null tissues when the wild-type allele was paternally
      derived. However, the phenotype was weaker than in Nrk-null placentas due to
      leaky Nrk expression from the inactivated X chromosome. Crossing of Nrk-null
      females to wild-type and Nrk-null males, as well as uterine transfer of Nrk-null
      fetuses to wild-type females, revealed that pregnant mice exhibit a severe defect
      in delivery when all fetuses/placentas are Nrk-null. In addition, Nrk was not
      expressed in female reproductive tissues such as the uterus and ovary, as well as
      the fetal amnion and yolk sac, in pregnant mice. Progesterone and estrogen levels
      in the maternal circulation and placenta, which control the timing of labor, were
      unaffected upon Nrk disruption. We thus provide evidence for a novel labor
      inducing fetoplacental signal that depends on the X chromosome and possibly
      arises from the placenta.

PMID- 21715336
TI  - Partial requirement of endothelin receptor B in spiral ganglion neurons for
      postnatal development of hearing.
AB  - Impairments of endothelin receptor B (Ednrb/EDNRB) cause the development of
      Waardenburg-Shah syndrome with congenital hearing loss, hypopigmentation, and
      megacolon disease in mice and humans. Hearing loss in Waardenburg-Shah syndrome
      has been thought to be caused by an Ednrb-mediated congenital defect of
      melanocytes in the stria vascularis (SV) of inner ears. Here we show that Ednrb
      expressed in spiral ganglion neurons (SGNs) in inner ears is required for
      postnatal development of hearing in mice. Ednrb protein was expressed in SGNs
      from WT mice on postnatal day 19 (P19), whereas it was undetectable in SGNs from
      WT mice on P3. Correspondingly, Ednrb homozygously deleted mice (Ednrb(-/-) mice)
      with congenital hearing loss showed degeneration of SGNs on P19 but not on P3.
      The congenital hearing loss involving neurodegeneration of SGNs as well as
      megacolon disease in Ednrb(-/-) mice were markedly improved by introducing an
      Ednrb transgene under control of the dopamine beta-hydroxylase promoter (Ednrb(-/
      );DBH-Ednrb mice) on P19. Neither defects of melanocytes nor hypopigmentation in
      the SV and skin in Ednrb(-/-) mice was rescued in the Ednrb(-/-);DBH-Ednrb mice.
      Thus, the results of this study indicate a novel role of Ednrb expressed in SGNs
      distinct from that in melanocytes in the SV contributing partially to postnatal
      hearing development.

PMID- 21715337
TI  - Amyloid-like fibrils from a domain-swapping protein feature a parallel, in
      register conformation without native-like interactions.
AB  - The formation of amyloid-like fibrils is characteristic of various diseases, but
      the underlying mechanism and the factors that determine whether, when, and how
      proteins form amyloid, remain uncertain. Certain mechanisms have been proposed
      based on the three-dimensional or runaway domain swapping, inspired by the fact
      that some proteins show an apparent correlation between the ability to form
      domain-swapped dimers and a tendency to form fibrillar aggregates. Intramolecular
      beta-sheet contacts present in the monomeric state could constitute
      intermolecular beta-sheets in the dimeric and fibrillar states. One example is an
      amyloid-forming mutant of the immunoglobulin binding domain B1 of streptococcal
      protein G, which in its native conformation consists of a four-stranded beta
      sheet and one alpha-helix. Under native conditions this mutant adopts a domain
      swapped dimer, and it also forms amyloid-like fibrils, seemingly in correlation
      to its domain-swapping ability. We employ magic angle spinning solid-state NMR
      and other methods to examine key structural features of these fibrils. Our
      results reveal a highly rigid fibril structure that lacks mobile domains and
      indicate a parallel in-register beta-sheet structure and a general loss of native
      conformation within the mature fibrils. This observation contrasts with
      predictions that native structure, and in particular intermolecular beta-strand
      interactions seen in the dimeric state, may be preserved in "domain-swapping"
      fibrils. We discuss these observations in light of recent work on related amyloid
      forming proteins that have been argued to follow similar mechanisms and how this
      may have implications for the role of domain-swapping propensities for amyloid
      formation.

PMID- 21715338
TI  - CCAAT/enhancer-binding protein delta mediates tumor necrosis factor alpha-induced
      Aurora kinase C transcription and promotes genomic instability.
AB  - Epidemiologic and clinical research indicates that chronic inflammation increases
      the risk of certain cancers, possibly through chromosomal instability. However,
      the mechanism of inflammation-dependent chromosomal instability associated with
      tumorigenesis is not well characterized. The transcription factor CCAAT/enhancer
      binding protein delta (C/EBPdelta, CEBPD) is induced by tumor necrosis factor
      alpha (TNFalpha) and expressed in chronically inflamed tissue. In this study, we
      show that TNFalpha promotes aneuploidy. Loss of CEBPD attenuated TNFalpha-induced
      aneuploidy, and CEBPD caused centromere abnormality. Additionally, TNFalpha
      induced CEBPD expression augmented anchorage-independent growth. We found that
      TNFalpha induced expression of aurora kinase C (AURKC) through CEBPD, and that
      AURKC also causes aneuploidy. Furthermore, high CEBPD expression correlated with
      AURKC expression in inflamed cervical tissue specimens. These data provide
      insight into a novel function for CEBPD in inducing genomic instability through
      the activation of AURKC expression in response to inflammatory signals.

PMID- 21715345
TI  - Inhibition of TLR3-mediated proinflammatory effects by Alkylphosphocholines in
      human retinal pigment epithelial cells.
AB  - PURPOSE. To elucidate the role of Toll-like receptor 3 (TLR3) in the pathogenesis
      of age-related macular degeneration (AMD) and to investigate the effect of
      alkylphosphocholines (APCs) on the TLR3-mediated expression of cytokines and
      growth factors in human retinal pigment epithelial (RPE) cells. METHODS.
      Confluent cultures of human RPE cells (ARPE-19) were stimulated with poly (I:C)
      RNA as a well-established ligand for TLR3. Cytokine profiles were determined by
      RT-PCR on the activation of TLR3. RPE cells were transfected with siRNA specific
      for TLR3 and RIG-1 to determine the receptors involved. The effect of
      preincubation of RPE cells with APCs on the expression level of target genes was
      assessed. RESULTS. Poly (I:C) RNA stimulation led to a dose-dependent increase in
      the expression of TLR3 and RIG-I. A significant increase in expression levels of
      IL-6, TNF-alpha, IL-8, MCP-1, ICAM-1, and BFGF was observed after poly (I:C) RNA
      stimulation (P < 0.05). This effect was time and dose dependent. No effect on
      PEDG or VEGF expression was seen. Transfection of RPE cells with siRNA specific
      for TLR3 reduced poly (I:C) RNA-induced mRNA expression of the genes (P < 0.05).
      Preincubation of RPE cells with APCs significantly reduced the poly (I:C) RNA
      induced expression of the target genes (P < 0.05). CONCLUSIONS. The authors
      demonstrate that the expression of proinflammatory cytokines and chemokines in
      RPE cells depends on the activation of TLR3. The induction of downstream gene
      expression is blocked by siRNA specific for TLR3 and alkylphosphocholines.
      Therefore, TLR3 should be considered a novel target in AMD therapy.

PMID- 21715346
TI  - Expansion of the CHN1 strabismus phenotype.
AB  - PURPOSE: Hyperactivating CHN1 mutations have been described in individuals with
      Duane retraction syndrome with or without vertical gaze abnormalities. This was a
      study of five family members with distinctive ocular dysmotility patterns that co
      segregated with a novel hyperactivating CHN1 mutation. METHODS: Participating
      members of a family segregating pleomorphic incomitant strabismus underwent
      ophthalmic examinations, and several underwent high-resolution magnetic resonance
      imaging (MRI) of the orbits and brain stem. Participant DNA was extracted and
      amplified for haplotype analysis encompassing the CHN1 region on chromosome
      2q31.1, and mutation analysis of the CHN1 gene, which encodes the Rac-GAP
      signaling protein alpha2-chimaerin. In vitro functional studies of the co
      inherited mutation were performed, including a Rac-GTP activation assay,
      quantification of alpha2-chimaerin translocation, and co-immunoprecipitation.
      RESULTS: All five clinically affected family members exhibited monocular or
      binocular supraduction deficits, three in the absence of Duane retraction
      syndrome. MRI in four affected individuals demonstrated small or absent abducens
      nerves in all four, small oculomotor nerve in one, and small optic nerves in
      three. Superior oblique muscle volume was also decreased in three of the
      individuals, supporting trochlear nerve hypoplasia. Strabismus segregated with
      the CHN1 locus and affected individuals harbored a c.443A>T CHN1 mutation
      (p.Y148F). In vitro, this novel mutation behaved similarly to previously reported
      CHN1 mutations underlying familial Duane syndrome, hyperactivating alpha2
      chimaerin by enhancing its dimerization and membrane association and lowering
      total intracellular Rac-GTP. CONCLUSIONS: Analysis of the current pedigree
      expands the phenotypic spectrum of hyperactivating CHN1 mutations to include
      vertical strabismus and supraduction deficits in the absence of Duane retraction
      syndrome.

PMID- 21715347
TI  - Corneal complications in streptozocin-induced type I diabetic rats.
AB  - PURPOSE. This study seeks to characterize corneal functions and complications in
      a streptozocin (STZ)-induced rat model of type I diabetes mellitus (DM) and to
      understand the pathogenesis of diabetic keratopathy. METHODS. DM was induced via
      STZ injection in Sprague-Dawley rats. Body weight, length, and corneal size were
      measured and compared with the age-matched normal controls. Corneal morphology
      and histology were evaluated with slit lamp, digital confocal microscopy and
      hematoxylin and eosin staining. Tear secretion was measured with cotton threads,
      and corneal sensitivity was determined with an esthesiometer. Protein expression
      and distribution were assessed with Western blotting and immunohistochemistry.
      Wound healing was determined using an in vivo corneal epithelial debridement
      model. RESULTS. Compared with the normal control rats, STZ rats had reduced body
      weight, and body length, but minimally affected corneal size. No significant
      changes in ocular surface regularity, corneal thickness, and morphology were
      noted in diabetic corneas. STZ rats showed stronger Rose Bengal staining,
      decreased tear secretion, slightly attenuated sensitivity, less innervation,
      delayed epithelial wound healing, and impaired epidermal growth factor receptor
      signaling in their corneas. While the expression of adherens junction protein
      beta-catenin, and tight junction proteins occludin and ZO-1 was unchanged, the
      formation of these junctions after wound closure was delayed. CONCLUSIONS.
      Pathogenesis of diabetic keratopathy involves multiple tissues and/or cell types
      and several events including reduced tear secretion, impaired innervation,
      weakened cell junction, and altered wound responses. These insights may prove
      useful for the clinical translation of evolving strategies for the management and
      treatment of diabetic corneal complications.

PMID- 21715348
TI  - Combined blockade of VEGFR-3 and VLA-1 markedly promotes high-risk corneal
      transplant survival.
AB  - PURPOSE. High-risk corneal transplantation refers to grafting performed on
      inflamed and highly vascularized host beds. It represents a clinical dilemma
      because the rejection rate can be as high as 90%, irrespective of current
      treatment modalities. This study was conducted to investigate whether combined
      blockade of VEGFR-3 (vascular endothelial growth factor receptor-3) and VLA-1
      (very late antigen-1) promotes high-risk transplant survival and how it
      correlates with corneal lymphangiogenesis and hemangiogenesis before and after
      transplantation. METHODS. High-risk corneal transplantation was performed between
      normal C57BL/6 (donor) and inflamed BALB/c (recipient) mice. The recipients were
      randomized to receive intraperitoneal injections of VEGFR-3 and VLA-1
      neutralizing antibodies or their controls twice a week for up to 8 weeks after
      transplantation. Corneal grafts were evaluated by ophthalmic slit-lamp
      biomicroscopy and analyzed by Kaplan-Meier survival curve. Additionally, whole
      mount corneas before and after transplantation were examined by immunofluorescent
      microscopic assays, and the correlation between lymphatic or blood vessel
      distribution and transplant outcome was analyzed. RESULTS. The combined blockade
      markedly promotes 90% survival of high-risk transplants. This strategy
      specifically modified host beds by selective inhibition of lymphangiogenesis but
      not hemangiogenesis. A strong correlation was also identified between high-risk
      transplant rejection and severe lymphatic invasion reaching the donor-graft
      border. CONCLUSIONS. These novel findings not only provide a new and potentially
      powerful strategy to promote high-risk transplant survival, they also confirm a
      critical role of high-degree lymphangiogenesis in mediating high-risk transplant
      rejection. Results from this study may also shed new light on our understanding
      and management of other lymphatic- and immune-related diseases in general.

PMID- 21715349
TI  - Fenofibric acid reduces fibronectin and collagen type IV overexpression in human
      retinal pigment epithelial cells grown in conditions mimicking the diabetic
      milieu: functional implications in retinal permeability.
AB  - PURPOSE: To determine whether fenofibric acid (FA) reduces high glucose (HG)
      induced basement membrane component overexpression and hyperpermeability in human
      retinal pigment epithelial (RPE) cells. METHODS: Retinal pigment epithelial cells
      (ARPE-19) were cultured for 18 days in normal glucose (5 mM) or HG (25 mM) medium
      and studied for the effects of FA on fibronectin (FN) and collagen IV (Coll IV)
      expression. During last 3 days of the experiment, 100 MUM FA was added to cells
      grown in HG medium or in HG medium plus IL-1beta (HG + IL-1beta) to mimic, at
      least in part, the inflammatory aspect of the diabetic milieu. Real-time RT-PCR
      was performed to determine FN and Coll IV mRNA levels, whereas protein levels
      were assessed by Western blot analyses. Cell monolayer morphology and barrier
      function were analyzed by confocal microscopy using specific antibodies against
      tight junction proteins, ZO-1, and claudin-1 and by measuring apical-basolateral
      movements of FITC-dextran, respectively. RESULTS: FN and Coll IV expression were
      significantly increased in RPE cells grown in HG or HG + IL-1beta medium compared
      with cells grown in normal medium. When cells grown in HG or HG + IL-1beta medium
      were treated with FA, significant reductions in FN and Coll IV expression were
      observed. In addition, exposure to FA decreased excess permeability in a dose
      dependent manner in cells grown in HG + IL-1beta medium. This effect was
      unrelated to changes in tight junction protein content. CONCLUSIONS: Findings
      from this study suggest that the downregulation of basement membrane components
      by FA may have a protective effect against outer blood-retinal barrier leakage
      associated with diabetic retinopathy.

PMID- 21715350
TI  - Vitamin D enhances corneal epithelial barrier function.
AB  - PURPOSE: The purpose of this study was to determine whether 25-hydroxyvitamin
      D(3) (25(OH)D(3)) and/or its active metabolite, 1alpha,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)), can enhance corneal epithelial barrier function. The authors
      also determined if corneas contain mRNA for the vitamin D receptor (VDR) and
      1alpha-hydroxylase, the enzyme required to convert 25(OH)D(3) to 1,25(OH)(2)D(3),
      and measured vitamin D metabolite concentrations in aqueous and vitreous humor.
      METHODS: RT-PCR was used to examine mouse, rabbit, and human corneal epithelial
      VDR and 1alpha-hydroxylase mRNA. Vitamin D metabolites were measured using a
      selective vitamin D derivatizing agent and mass spectroscopy. Barrier function
      experiments were performed by measuring inulin permeability (IP) and/or
      transepithelial resistance (TER) in control, 25(OH)D(3)-, and 1,25(OH)(2)D(3)
      treated human and rabbit corneal epithelial monolayers cultured on permeable
      inserts. Ca(2+) was removed, then reintroduced to the culture medium while IP and
      TER readings were taken. Occludin levels were examined using Western blotting.
      RESULTS: All corneal samples were positive for both VDR and 1alpha-hydroxylase
      mRNA. All vitamin D metabolites except for unhydroxylated vitamin D(3) were
      detected in aqueous and vitreous humor. Epithelial cells showed increased TER,
      decreased IP, and increased occludin levels when cultured with 25(OH)D(3) and
      1,25(OH)(2)D(3). CONCLUSIONS: We conclude that corneas contain mRNA for VDR and
      1alpha-hydroxylase as well as significant vitamin D concentrations. 25(OH)D(3)
      and its active metabolite 1,25(OH)(2)D(3), both enhance corneal epithelial
      barrier function.

PMID- 21715351
TI  - A 112 kb deletion in chromosome 19q13.42 leads to retinitis pigmentosa.
AB  - PURPOSE. This study sets out to identify novel mutations in PRPF31 in a cohort of
      autosomal dominant retinitis pigmentosa (adRP) patients with a history of
      nonpenetrance in the family. METHODS. Twenty-one patients with history of
      nonpenetrant autosomal dominant retinitis pigmentosa were selected; all underwent
      full ophthalmic examination. Multiplex ligation-dependent probe analysis (MLPA)
      was performed and, where a deletion was found, further family members were
      recruited. An individual suspected to harbor a large deletion was used as a
      positive control. Analysis of single nucleotide polymorphisms in the upstream
      region was used to determine the extent of the deletion, and the breakpoint was
      then characterized by PCR and sequencing. RESULTS. In one family, multiplex
      ligation-dependent probe analysis revealed a novel large deletion in 19q13.4
      encompassing exons 1 to 13 of the PRPF31 gene. The mutation was characterized as
      a deletion of 112 kilobase (kb), encompassing over 90% of PRPF31 and five
      upstream genes: TFPT, OSCAR, NDUFA3, TARM-1, and VSTM-1. The breakpoint in the
      positive control family was also characterized. The mechanism of deletion in both
      families was Alu-mediated nonallelic homologous recombination. CONCLUSIONS. This
      study describes two large deletions, one in a previously reported family and one
      in a new family: the latter represents the largest deletion yet described on
      chromosome 19 and the first report of the involvement of VSTM-1. Remarkably,
      heterozygous deletion of this large region (encompassing six genes) produces
      little or no other clinical disease besides retinitis pigmentosa.

PMID- 21715352
TI  - Quantitative evaluation of retinal response to laser photocoagulation using dual
      wavelength fundus autofluorescence imaging in a small animal model.
AB  - PURPOSE: To demonstrate the usefulness of dual-wavelength fundus autofluorescence
      (FAF) imaging for noninvasive, quantitative monitoring of dynamic changes
      associated with healing of retinal photocoagulation lesions in a small animal
      model. METHODS: Brown Norway rats, exhibiting substantial age-dependent
      lipofuscin autofluorescence, were used to characterize the kinetics of FAF
      recovery after retinal photocoagulation. An argon laser with a beam diameter of
      100 MUm, exposure duration of 0.1 seconds, and a range of laser powers (8-22 mW)
      were used to create subthreshold, threshold, and suprathreshold lesions. A
      modified retinal angiograph was used to obtain dual-wavelength FAF images at 488
      and 514 nm to quantify and monitor changes in retinal fluorescence up to 6
      months. RESULTS: Compared to white light funduscopy, the FAF images exhibited
      heightened definition and clarity of lesion boundaries immediately after laser
      exposure. No significant reduction in FAF was measured at or below laser powers
      of 8 mW. Furthermore, a linear, dose-dependent decrease in FAF (R(2) = 0.9605)
      was observed immediately after laser exposures of 13 to 22 mW. Complete recovery
      of baseline FAF was observed for 13.5 and 16 mW exposures at 3 weeks and 4
      months, respectively. However, retinal damage was still evident at 6 months after
      suprathreshold exposure induced using 22 mW laser power. CONCLUSIONS: The
      accumulation of lipofuscin in the aged Brown Norway rat makes it a suitable small
      animal model for the characterization of laser-induced injury in the retina based
      on FAF. Dual-wavelength FAF measurements provide a sensitive, quantitative,
      noninvasive means of monitoring recovery of laser-induced retinal injury.

PMID- 21715353
TI  - Retinal oximetry in primary open-angle glaucoma.
AB  - PURPOSE. To determine whether retinal vessel oxygen saturation is affected in
      primary open-angle glaucoma (POAG) patients. METHODS. Retinal oxygen saturation
      in patients with POAG was measured in retinal vessels with a spectrophotometric
      retinal oximeter in darkness, and visual fields were obtained. Oxygen tension
      (Po(2)) was calculated from oxygen saturation values. Statistical analysis was
      performed using Pearson's correlation and Student's t-test. RESULTS. Mean oxygen
      saturation in venules was higher in persons with poor visual fields (68% +/- 4%,
      mean +/- SD) than in those with good visual fields (62% +/- 3%; P = 0.0018). The
      mean arteriovenous difference in oxygen saturation was lower in persons with poor
      visual fields (30% +/- 4%, n = 9) than in those with good visual fields (37% +/-
      4%; P = 0.0003; n = 12). No correlation was found between saturation in retinal
      arterioles and visual field mean defect (n = 31; r = -0.16; P = 0.38). Oxygen
      saturation in retinal venules correlated positively with worsening visual field
      mean defect (r = 0.43; P = 0.015). Arteriovenous difference in oxygen saturation
      decreased significantly as the visual field mean defect worsened (r = -0.55; P =
      0.0013). Mean Po(2) in venules was 38 +/- 3 mm Hg. It was significantly higher in
      persons with poor visual field fields (40 +/- 3 mm Hg) than in those with good
      visual fields (36 +/- 2 mm Hg; P = 0.0016). CONCLUSIONS. Deeper glaucomatous
      visual field defects are associated with increased oxygen saturation in venules
      and decreased arteriovenous difference in retinal oxygen saturation. The data
      suggest that oxygen metabolism is affected in the glaucomatous retina, possibly
      related to tissue atrophy.

PMID- 21715354
TI  - Ocular perfusion pressure and the incidence of glaucoma: real effect or artifact?
      The Rotterdam Study.
AB  - PURPOSE: To determine the association between the ocular perfusion pressure (OPP;
      essentially the difference between the blood pressure and the intraocular
      pressure [IOP]) and incident open-angle glaucoma (OAG). METHODS: A subset of 3882
      participants of the population-based Rotterdam Study for whom data from
      ophthalmic examinations at baseline and follow-up and blood pressure measurements
      at baseline were available, and who did not have OAG at baseline, were included.
      Associations between the mean, systolic and diastolic OPP, and incident OAG were
      assessed using Cox regression models adjusted for age and sex, with and without
      adjustment for IOP. RESULTS: During a mean follow-up of 9.8 years, 103
      participants (2.7%) developed OAG. The association between the mean OPP and
      incident OAG was not significant (hazard ratio 0.995 per mm Hg increase in mean
      OPP; 95% confidence interval 0.971-1.019) when adjusted for IOP, but became
      significant if not adjusted for IOP (0.968; 0.945-0.992). The systolic and
      diastolic OPP showed a pattern similar to that of the mean OPP, though less
      significant. CONCLUSIONS: The OPP appears to be associated with incident OAG but
      this association seems to be due to the fact that the IOP, a strong risk factor
      for OAG, is part of the OPP, rather than that OPP is an independent OAG risk
      factor itself.

PMID- 21715355
TI  - Posterior (outward) migration of the lamina cribrosa and early cupping in monkey
      experimental glaucoma.
AB  - PURPOSE: To quantify the lamina cribrosa insertion into the peripapillary sclera
      and optic nerve pia in normal (N) and early experimental glaucoma (EEG) monkey
      eyes. METHODS: Perfusion-fixed optic nerve heads (ONHs) from 21 animals were
      digitally reconstructed three dimensionally and delineated. Anterior Laminar
      Insertion Position (ALIP), Posterior Laminar Insertion Position (PLIP), Laminar
      Insertion Length (LIL; distance between the anterior and posterior laminar
      insertions), and Scleral Thickness (at the Anterior Sub-arachnoid space) were
      calculated for each ONH. Animals were pooled into four groups based on the kill
      condition (N vs. EEG) and perfusion IOP (10, 30, or 45 mm Hg) of each eye: N10
      N10 (n = 6), N30/45-N10 (n = 6), EEG10-N10 (n = 3), and EEG30/45-N10 (n = 6).
      Glaucomatous EEG versus N eye differences in each group and each animal were
      required not only to achieve statistical significance (P < 0.05) but also to
      exceed physiologic intereye differences within the bilaterally normal groups.
      RESULTS: ALIP was significantly posterior (outward) in the EEG compared with N10
      eyes of the EEG30/45-N10 group and 5 of 9 individual EEG eyes (difference range,
      12-49 MUm). PLIP was significantly posterior in the EEG eyes of both EEG groups
      and in 6 of 9 individual EEG eyes (range, 25-83 MUm). LIL ranged from 90 to 190
      MUm in normal eyes and was significantly increased within the EEG eyes of both
      EEG groups and in 7 of 9 individual EEG eyes (difference range, 30-47 MUm).
      CONCLUSIONS: Posterior migration of the lamina cribrosa is a component of early
      cupping in monkey EEG.

PMID- 21715356
TI  - Altered expression of the transcription factor Mef2c during retinal degeneration
      in Rpe65-/- mice.
AB  - PURPOSE: To investigate the role of the myocyte enhancer factor 2 (Mef2)
      transcription factor family in retinal diseases, Mef2c expression was assessed
      during retinal degeneration in the Rpe65(-/-) mouse model of Leber's congenital
      amaurosis (LCA). Mef2c-dependent expression of photoreceptor-specific genes was
      further addressed. METHODS: Expression of Mef2 members was analyzed by
      oligonucleotide microarray, quantitative PCR (qPCR), and in situ hybridization.
      Mef2c-dependent transcriptional activity was assayed by luciferase assay in
      HEK293T cells. RESULTS: Mef2c was the only Mef2 member markedly downregulated
      during retinal degeneration in Rpe65(-/-) mice. Mef2c mRNA level was decreased by
      more than 2-fold at 2 and 4 months and by 3.5-fold at 6 months in retinas of
      Rpe65(-/-) mice. Downregulation of Mef2c at the protein level was confirmed in
      Rpe65(-/-) retinas. The decrease in Mef2c mRNA levels in the developing Rpe65(-/
      ) retinas from postnatal day (P) 13 onward was concomitant with the decreased
      expression of the rod-specific transcription factors Nrl and Nr2e3. Nrl was
      further shown to drive Mef2c transcriptional activity, supporting a physiological
      role for Mef2c in the retina. In addition, Mef2c appeared to act as a
      transcriptional repressor of its own expression and the expression of the retina
      specific retinal G-protein coupled receptor (Rgr), rhodopsin, and M-opsin genes.
      CONCLUSIONS: These findings highlight the early altered regulation of the rod
      specific transcriptional network in Rpe65-related disease. They also indicate
      that Mef2c may act as a novel transcription factor involved in the development
      and the maintenance of photoreceptor cells.

PMID- 21715357
TI  - The impact of acutely elevated intraocular pressure on the porcine optic nerve
      head.
AB  - PURPOSE: To investigate the effects of acute elevations in intraocular pressure
      (IOP) on the cup, prelaminar, and lamina cribrosa regions of the porcine optic
      nerve head (ONH). METHODS: Ex vivo imaging of 10 porcine ONHs was performed using
      spectral-domain optical coherence tomography (OCT). The IOP was manipulated with
      a pressure head and measured with a pressure transducer. Reference scans were
      taken at 0 mm Hg, before further scanning was performed at 7-mm Hg steps, up to
      49 mm Hg. Morphometric parameters were measured across centrally located OCT B
      scans at different IOPs, and the relationship between IOP and changes in these
      parameters was analyzed. RESULTS: As IOP increased from 0 to 49 mm Hg, mean cross
      sectional cup area increased (28% +/- 3%, P < 0.001), lamina cribrosa area
      decreased (18% +/- 2%, P < 0.001), and prelaminar tissue area decreased (5.5% +/-
      0.5%, P < 0.001). Multivariate regression demonstrated that most of the change in
      cup area is associated with changes in both lamina cribrosa position and
      thickness (r = 0.89, P < 0.001). CONCLUSIONS: Acute elevations in IOP were shown
      to result in posterior displacement of ONH, as well as lamina cribrosa and
      prelaminar tissue deformation in the porcine ONH.

PMID- 21715358
TI  - The importance of minor salivary gland biopsy in prediction of lymphoma in
      Sjogren's syndrome: should we be obtaining more information about prognosis from
      minor salivary gland samples?

PMID- 21715359
TI  - Lymphoid organisation in labial salivary gland biopsies is a possible predictor
      for the development of malignant lymphoma in primary Sjogren's syndrome.
AB  - OBJECTIVE: The development of non-Hodgkin's lymphoma (NHL) confers a high risk of
      mortality in primary Sjogren's syndrome (pSS) patients, but the sensitivity and
      specificity of proposed lymphoma predictors are insufficient for practical use.
      The performance of lymphoid organisation in the form of germinal centre (GC)-like
      lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as
      a potential lymphoma-predicting biomarker. METHODS: Labial salivary gland tissue
      biopsies available from two Swedish pSS research cohorts (n=175) were re
      evaluated by light microscopy in a blind study in order to identify GC-like
      structures as a sign of ectopic lymphoid tissue formation and organisation. A
      linkage study was performed with the Swedish Cancer Registry for lymphoma
      identification. The risk of developing NHL in GC-positive patients in comparison
      with GC-negative patients was evaluated using Kaplan-Meier statistics and log
      rank test. Associations between GC-like structures and clinical and/or laboratory
      disease markers were also determined using chi(2) or Fisher's exact tests.
      RESULTS: At diagnosis, 25% of pSS patients had GC-like structures in their
      salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-)
      developed NHL during 1855 patient-years at risk, with a median onset of 7 years
      following the initial diagnostic salivary gland biopsy. Six of the seven patients
      had GC-like structures at diagnosis; the remaining patient was GC negative at the
      time of diagnosis (p=0.001). CONCLUSIONS: The detection of GC-like structures by
      light microscopy in pSS diagnostic salivary biopsies is proposed as a highly
      predictive and easy-to-obtain marker for NHL development. This allows for risk
      stratification of patients and the possibility to initiate preventive B-cell
      directed therapy.

PMID- 21715360
TI  - The first case of primary testicular germ cell tumor containing nephroblastoma as
      the only one non-germ cell component.
AB  - Adult extrarenal nephroblastomas (Wilms' tumor) are extremely rare tumors. They
      show a higher incidence of non-seminomatous elements and these so-called
      'teratoid' Wilms' tumors are suggested to be of germ cell origin. To date,
      however, the number of reported cases with gonadal teratoma containing
      nephroblastoma is very low, and due to this reason, there are no standardized
      criteria for the categorization and treatment of these lesions. To our knowledge,
      the first case of nephroblastoma arising in a non-atrophic testis has been
      reported and it is associated with a teratoma as morphologically identifiable
      germ cell tumor and rhabdomyosarcoma as a second non-germ cell element. We report
      the second case of an adult nephroblastoma that arose within the primary
      testicular teratoma in a non-atrophic testis. Teratoma and nephroblastoma within
      the same testis may have an important point to clarify the developmental
      mechanism in nephroblastomatous differentiation of germ cell tumors.

PMID- 21715361
TI  - Phase II study of erlotinib as third-line monotherapy in patients with advanced
      non-small-cell lung cancer without epidermal growth factor receptor mutations.
AB  - OBJECTIVE: There are few standard therapeutic options beyond second-line
      treatment. We aimed to evaluate the efficacy and safety of erlotinib monotherapy
      as third-line chemotherapy in patients with advanced non-small-cell lung cancer
      without epidermal growth factor receptor mutations. METHODS: In this phase II
      trial, patients who did not have epidermal growth factor receptor mutations and
      who had previously received two cytotoxic chemotherapy regimens containing
      platinum were treated with erlotinib (150 mg, per os) until disease progression
      or unacceptable toxicity. RESULTS: Twenty patients were eligible for the
      assessment of efficacy and safety. Three cases showed a partial response, and
      eight cases showed stable disease with an overall response rate of 15.0% (95%
      confidence interval: 5.2-36.0%) and a disease control rate of 55.0% (95%
      confidence interval: 34.2-74.2%). Median progression-free survival and overall
      survival time were 2.1 and 6.7 months, respectively. Although dose reduction was
      required in one patient because of skin toxicity, grade 3/4 toxicity or pulmonary
      disease was not observed. CONCLUSIONS: Erlotinib as third-line therapy showed an
      acceptable response rate, survival time and toxicity. It could be a potential
      third-line therapy for patients without epidermal growth factor receptor
      mutations.

PMID- 21715362
TI  - Concomitant weekly cisplatin and radiotherapy for head and neck cancer.
AB  - OBJECTIVE: The most common chemoradiotherapy regimen is high-dose (100 mg/m(2))
      three-weekly cisplatin with concomitant radiotherapy; however, this protocol is
      associated with acute and late toxicities. Here, we reviewed the dose intensity
      and toxicity for concomitant weekly cisplatin and radiotherapy in patients with
      head and neck cancer. METHODS: Fifty-three patients with untreated head and neck
      cancer were enrolled and evaluated at our institution from April 2006 to April
      2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with
      radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily
      fractions over 7 weeks. RESULTS: Fifty-one patients (96.2%) received the full
      dose of radiotherapy, while the course was disrupted by adverse events in two.
      Over the course of the chemotherapy, 31 patients (58.5%) received more than 200
      mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who
      died of sepsis after completing treatment. The 2-year overall survival rate and
      local progression-free rate for all patients were 93.7% and 88.0%, respectively.
      The primary site showed a complete response in 52 patients (98.1%) and a partial
      response in 1 patient (1.9%). The primary disease was well controlled by
      chemoradiotherapy in 47 patients (88.7%). CONCLUSIONS: Weekly cisplatin could be
      easier to manage than three-weekly cisplatin, because patients can be monitored
      more regularly for toxicity allowing the schedule to be altered if required. This
      regimen appears to be a suitable alternative to three-weekly high-dose cisplatin
      with concomitant radiotherapy.

PMID- 21715363
TI  - Phase II study of gefitinib as a first-line therapy in elderly patients with
      pulmonary adenocarcinoma: West Japan Thoracic Oncology Group Study 0402.
AB  - OBJECTIVE: Elderly patients prefer to receive less-toxic therapy. Monotherapy
      using drugs such as vinorelbine, gemcitabine or docetaxel is a preferable
      chemotherapy in elderly patients with advanced non-small-cell lung cancer.
      Gefitinib shows remarkable efficacy in patients with advanced non-small-cell lung
      cancer, who have activating epidermal growth factor receptor mutations.
      Adenocarcinoma histology is related to these mutations. Therefore, we conducted a
      phase II study of gefitinib as a first-line therapy in elderly patients with
      pulmonary adenocarcinoma. METHODS: Eligible patients were 70 years or older, had
      pulmonary adenocarcinoma, stage IIIB or IV disease, an Eastern Cooperative
      Oncology Group performance status of 0-2 and adequate organ functions. Patients
      were treated with oral gefitinib 250 mg daily until disease progression or
      unacceptable toxicity. RESULTS: Thirty-one patients were enrolled, of whom 30
      were eligible. The median age was 78.5 years. The response rate was 20%, the
      disease control rate was 47%, the median progression-free survival was 2.7 months
      and the median overall survival was 11.9 months. Narrowing it down to those who
      had never smoked, the response rate increased to 43%, the disease control rate
      increased to 57%, the median progression-free survival prolonged to 7.1 months
      and the median overall survival prolonged to 13.0 months. The most frequent
      toxicity was rash. Other major toxicities were diarrhea, anorexia, liver
      dysfunction and anemia. These toxicities were mild and easily managed.
      CONCLUSIONS: Gefitinib as a first-line therapy is active and well tolerated in
      elderly patients with pulmonary adenocarcinoma, especially in those who have
      never smoked.

PMID- 21715364
TI  - Multicenter phase II study of gemcitabine and S-1 combination therapy (GS
      Therapy) in patients with metastatic pancreatic cancer.
AB  - OBJECTIVE: The aim of this multicenter Phase II study was to assess the efficacy
      and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic
      cancer. METHODS: Chemotherapy-naive patients with histologically or cytologically
      proven metastatic pancreatic adenocarcinoma were eligible for this study.
      Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and
      8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated
      every 3 weeks. RESULTS: A total of 55 patients were included and the efficacy and
      toxicity were analyzed in 54 patients who received at least one dose of
      gemcitabine and S-1 combination therapy. Although no complete response was seen,
      a partial response was achieved in 24 patients, resulting in an overall response
      rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free
      survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median
      overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with
      a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia
      (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%).
      Hematological toxicity was mostly transient and there was only one episode of
      febrile neutropenia >=Grade 3. CONCLUSIONS: Gemcitabine and S-1 combination
      therapy produced a high response rate with good survival in patients with
      metastatic pancreatic cancer. A randomized Phase III study to confirm the
      efficacy of gemcitabine and S-1 combination therapy is ongoing.

PMID- 21715365
TI  - Clinical significance of positive Delphian node in supracricoid laryngectomy with
      cricohyoidoepiglottopexy.
AB  - OBJECTIVE: A positive Delphian node is known to predict a poor prognosis in
      laryngeal cancer. To elucidate the clinical significance of positive Delphian
      node metastasis in supracricoid laryngectomized patients, we conducted a thorough
      clinical review. METHODS: We reviewed clinical data from 65 patients who
      underwent supracricoid laryngectomy with cricohyoidoepiglottopexy; in these
      patients, the Delphian node was examined by frozen section as a routine process.
      Incidence, positivity rates and clinical impact of the positive Delphian node
      were analyzed. RESULTS: The presence of the Delphian node was detected in 27 of
      65 (41.5%) patients; among these 27 patients, 3 (3/65 = 4.6%) were positive for
      metastasis. Case 1 (pT3N2b) died of lung metastases 32 months after supracricoid
      laryngectomy with cricohyoidoepiglottopexy. Case 2 (pT4N2c) underwent conversion
      to total laryngectomy during supracricoid laryngectomy with
      cricohyoidoepiglottopexy because of unexpected submucosal lymphatic infiltration;
      this patient is currently alive with disease 23 months after surgery. Case 3
      (T3N1) is currently alive without disease 48 months after surgery. CONCLUSIONS:
      The positive Delphian node is exclusively encountered in advanced laryngeal
      cancers and suggests an ominous outcome. Sufficient dissection of the
      paratracheal and lateral neck nodes is recommended. Delphian node evaluation is
      advised for all supracricoid laryngectomy surgeries.

PMID- 21715366
TI  - Dry matter partitioning models for the simulation of individual fruit growth in
      greenhouse cucumber canopies.
AB  - BACKGROUND AND AIMS: Growth imbalances between individual fruits are common in
      indeterminate plants such as cucumber (Cucumis sativus). In this species, these
      imbalances can be related to differences in two growth characteristics, fruit
      growth duration until reaching a given size and fruit abortion. Both are related
      to distribution, and environmental factors as well as canopy architecture play a
      key role in their differentiation. Furthermore, events leading to a fruit
      reaching its harvestable size before or simultaneously with a prior fruit can be
      observed. Functional-structural plant models (FSPMs) allow for interactions
      between environmental factors, canopy architecture and physiological processes.
      Here, we tested hypotheses which account for these interactions by introducing
      dominance and abortion thresholds for the partitioning of assimilates between
      growing fruits. METHODS: Using the L-System formalism, an FSPM was developed
      which combined a model for architectural development, a biochemical model of
      photosynthesis and a model for assimilate partitioning, the last including a
      fruit growth model based on a size-related potential growth rate (R(P)). Starting
      from a distribution proportional to R(P), the model was extended by including
      abortion and dominance. Abortion was related to source strength and dominance to
      sink strength. Both thresholds were varied to test their influence on fruit
      growth characteristics. Simulations were conducted for a dense row and a sparse
      isometric canopy. KEY RESULTS: The simple partitioning models failed to simulate
      individual fruit growth realistically. The introduction of abortion and dominance
      thresholds gave the best results. Simulations of fruit growth durations and
      abortion rates were in line with measurements, and events in which a fruit was
      harvestable earlier than an older fruit were reproduced. CONCLUSIONS: Dominance
      and abortion events need to be considered when simulating typical fruit growth
      traits. By integrating environmental factors, the FSPM can be a valuable tool to
      analyse and improve existing knowledge about the dynamics of assimilates
      partitioning.

PMID- 21715367
TI  - Inhalation with NDS27 attenuates pulmonary neutrophilic inflammation in recurrent
      airway obstruction.

PMID- 21715368
TI  - Unexpected collapse in apparently healthy newborns--a prospective national study
      of a missing cohort of neonatal deaths and near-death events.
AB  - BACKGROUND: Sudden and unexpected postnatal collapse (SUPC) of a healthy newborn
      infant is a rare event, which carries a high risk of mortality and significant
      neurodisability in survivors. An underlying condition can be found in 60% of
      cases who undergo detailed postmortem but in the remainder there are important
      associations with prone position, breast feeding and primiparous status. The
      authors undertook a prospective study to ascertain the population incidence of
      SUPC in the UK. METHODS: Cases were referred through the British Paediatric
      Surveillance Unit reporting scheme over a 13-month period. Infants were at >=37
      weeks of gestation, had an Apgar score of >=8 at 5 min, collapsed within 12 h in
      hospital requiring positive pressure ventilation and either died or received
      ongoing intensive care. Data were collected on maternal and infant
      characteristics, clinical investigations and 1-year outcome. FINDINGS: 45 cases
      were reported, an incidence of 0.05/1000 live births of whom 12 infants died. In
      15/45 infants, an underlying disease/abnormality was determined. In 30/45 cases
      (0.035/1000 live births), no such cause was found, but in 24, the
      clinical/pathological diagnosis was airway obstruction during breast feeding or
      in prone position. Mothers were commonly primiparous and unattended by clinical
      staff before collapse was recognised. Approach to investigation was highly
      disparate and frequently very limited. Of the 30 infants with no underlying
      disease/abnormality, 22 (73%) developed a postasphyxial encephalopathy and 10 had
      a poor outcome (33%)--5 died and 5 had neurological sequelae at 1 year.
      INTERPRETATION: SUPC is rare in any one centre and there is no standard approach
      to investigation. In those cases where collapse is not due to an underlying
      abnormality, breast feeding and prone position are important associations.
      Guidelines for safe postnatal care of infants should include appropriate
      vigilance of infants particularly where mothers are primiparous or where ability
      to assess the baby may be impaired.

PMID- 21715370
TI  - A critical review of the effects of medical Qigong on quality of life, immune
      function, and survival in cancer patients.
AB  - BACKGROUND: Due to the limitations and side effects of conventional cancer
      treatment, especially in relation to quality of life (QOL), patients are
      increasingly utilizing complementary and alternative medicine (CAM) to supplement
      health-related outcomes. However, evidence for the safety and efficacy of such
      treatments is lacking. The purpose of the current review was to investigate
      evidence for the role of one CAM, medical Qigong (MQ), in supportive care.
      METHODS: The literature was searched for reported effects of MQ in improving QOL,
      immune function, and survival in cancer patients. RESULTS: Although many studies
      possessed methodological limitations and small sample sizes, encouraging evidence
      was found for the effects of MQ on these health-related outcomes. More robust
      evidence in the form of randomized controlled trials with larger sample sizes
      also reflected positive results for the role of MQ in improving QOL, mood and
      fatigue parameters, and reducing inflammation. CONCLUSION: Given such encouraging
      results, further research is recommended in methodologically sound approaches to
      further delineate the action of MQ. These findings support the utilization of MQ
      by cancer patients and the place for such programs in comprehensive cancer care.

PMID- 21715371
TI  - Effects of sweet bee venom pharmacopuncture treatment for chemotherapy-induced
      peripheral neuropathy: a case series.
AB  - OBJECTIVE: This is a case series reporting safety and degree of response to 1
      dose level of sweet bee venom pharmacopuncture (SBVP) or melittin as a symptom
      control therapy for chemotherapy-induced peripheral neuropathy (CIPN). SETTING:
      All treatments were conducted at the East West Cancer Center (EWCC), Dunsan
      Oriental Hospital, Daejeon University, Republic of Korea, an institution that
      uses complementary therapies for cancer patients. METHODS: Five consecutive
      patients with CIPN were referred to the EWCC from March 20, 2010, to April 10,
      2010. Patients with World Health Organization Chemotherapy-Induced Peripheral
      Neuropathy (WHO CIPN) grade 2 or more were treated with SBVP for 3 treatment
      sessions over a 1-week period. Measures of efficacy and safety. Validated Visual
      Analog System (VAS) pain scale, WHO CIPN grade, and Functional Assessment of
      Cancer Therapy-General (FACT-G) were compared before and after the 1-week course
      of treatment. To ensure the safety of SBVP, pretreatment skin response tests were
      given to patients to avoid any potential anaphylactic adverse effects. All
      patients were closely examined for any allergenic responses following each
      treatment session. RESULTS: One patient discontinued treatment after the first
      session, and 4 patients completed all treatment sessions. Using each patient as
      their own comparator, marked improvements of VAS, WHO CIPN grade, and physical
      section scores of FACT-G were seen in 3 patients. Most important, there were no
      related adverse side effects found. CONCLUSION: This safety results of the SBVP
      therapy merits further investigations in a larger size trial for it to develop
      into a potential intervention for managing CIPN symptoms. This study will be
      extended to a dose-response evaluation to further establish safety and response,
      prior to a randomized trial.

PMID- 21715372
TI  - Internal standard-based analysis of microarray data2--analysis of functional
      associations between HVE-genes.
AB  - In this work we apply the Internal Standard-based analytical approach that we
      described in an earlier communication and here we demonstrate experimental
      results on functional associations among the hypervariably-expressed genes (HVE
      genes). Our working assumption was that those genetic components, which initiate
      the disease, involve HVE-genes for which the level of expression is
      undistinguishable among healthy individuals and individuals with pathology. We
      show that analysis of the functional associations of the HVE-genes is indeed
      suitable to revealing disease-specific differences. We show also that another
      possible exploit of HVE-genes for characterization of pathological alterations is
      by using multivariate classification methods. This in turn offers important clues
      on naturally occurring dynamic processes in the organism and is further used for
      dynamic discrimination of groups of compared samples. We conclude that our
      approach can uncover principally new collective differences that cannot be
      discerned by individual gene analysis.

PMID- 21715373
TI  - Emulsified BMVC derivative induced filtration for G-quadruplex DNA structural
      separation.
AB  - A novel method based on emulsion/filtration is introduced for G-quadruplex DNA
      structural separation. We first synthesized a lipophilic analogue of BMVC, 3,6
      Bis(1-methyl-4-vinylpyridinium)-9-(12'-bromododecyl) carbazole diiodide (BMVC-12C
      Br), which can form an oil-in-water (o/w) phase emulsion. Due to the binding
      preferences of BMVC-12C-Br emulsion to some specific DNA structures, the large
      emulsion (~2 um) bound DNA was separated from the small free DNA in the filtrate
      by a 0.22 um pore size MCE membrane. This method is able to isolate the non
      parallel G-quadruplexes from the parallel G-quadruplexes and the linear duplexes
      from both G-quadruplexes. In addition, this method allows us not only to
      determine the absence of the parallel G-quadruplexes of d(T(2)AG(3))(4) and the
      presence of the parallel G-quadruplexes of d(T(2)AG(3))(2) in K(+) solution, but
      also to verify structural conversion from antiparallel to parallel G-quadruplexes
      of d[AG(3)(T(2)AG(3))(3)] in K(+) solution under molecular PEG condition.
      Moreover, this emulsion can separate the non-parallel G-quadruplexes of
      d(G(3)CGCG(3)AGGAAG(5)CG(3)) monomer from the parallel G-quadruplexes of its
      dimer in K(+) solution. Together with NMR spectra, one can simplify the spectra
      for both the free DNA and the bound DNA to establish a spectrum-structure
      correlation for further structural analysis.

PMID- 21715374
TI  - Thrombin-aptamer recognition: a revealed ambiguity.
AB  - Aptamers are structured oligonucleotides that recognize molecular targets and can
      function as direct protein inhibitors. The best-known example is the thrombin
      binding aptamer, TBA, a single-stranded 15-mer DNA that inhibits the activity of
      thrombin, the key enzyme of coagulation cascade. TBA folds as a G-quadruplex
      structure, as proved by its NMR structure. The X-ray structure of the complex
      between TBA and human alpha-thrombin was solved at 2.9-A resolution, but did not
      provide details of the aptamer conformation and the interactions with the protein
      molecule. TBA is rapidly processed by nucleases. To improve the properties of
      TBA, a number of modified analogs have been produced. In particular, a modified
      TBA containing a 5'-5' polarity inversion site, mTBA, has higher stability and
      higher affinity toward thrombin with respect to TBA, although it has a lower
      inhibitory activity. We present the crystal structure of the thrombin-mTBA
      complex at 2.15-A resolution; the resulting model eventually provides a clear
      picture of thrombin-aptamers interaction, and also highlights the structural
      bases of the different properties of TBA and mTBA. Our findings open the way for
      a rational design of modified aptamers with improved potency as anticoagulant
      drugs.

PMID- 21715375
TI  - Efficient gene targeting mediated by a lentiviral vector-associated meganuclease.
AB  - Gene targeting can be achieved with lentiviral vectors delivering donor sequences
      along with a nuclease that creates a locus-specific double-strand break (DSB).
      Therapeutic applications of this system would require an appropriate control of
      the amount of endonuclease delivered to the target cells, and potentially toxic
      sustained expression must be avoided. Here, we show that the nuclease can be
      transferred into cells as a protein associated with a lentiviral vector particle.
      I-SceI, a prototypic meganuclease from yeast, was incorporated into the virions
      as a fusion with Vpr, an HIV accessory protein. Integration-deficient lentiviral
      vectors containing the donor sequences and the I-SceI fusion protein were tested
      in reporter cells in which targeting events were scored by the repair of a
      puromycin resistance gene. Molecular analysis of the targeted locus indicated a 2
      fold higher frequency of the expected recombination event when the nuclease was
      delivered as a protein rather than encoded by a separate vector. In both systems,
      a proportion of clones displayed multiple integrated copies of the donor
      sequences, either as tandems at the targeted locus or at unrelated loci. These
      integration patterns were dependent upon the mode of meganuclease delivery,
      suggesting distinct recombination processes.

PMID- 21715376
TI  - Translation-competent 48S complex formation on HCV IRES requires the RNA-binding
      protein NSAP1.
AB  - Translation of many cellular and viral mRNAs is directed by internal ribosomal
      entry sites (IRESs). Several proteins that enhance IRES activity through
      interactions with IRES elements have been discovered. However, the molecular
      basis for the IRES-activating function of the IRES-binding proteins remains
      unknown. Here, we report that NS1-associated protein 1 (NSAP1), which augments
      several cellular and viral IRES activities, enhances hepatitis C viral (HCV) IRES
      function by facilitating the formation of translation-competent 48S ribosome-mRNA
      complex. NSAP1, which is associated with the solvent side of the 40S ribosomal
      subunit, enhances 80S complex formation through correct positioning of HCV mRNA
      on the 40S ribosomal subunit. NSAP1 seems to accomplish this positioning function
      by directly binding to both a specific site in the mRNA downstream of the
      initiation codon and a 40S ribosomal protein (or proteins).

PMID- 21715377
TI  - Transfection of plant mitochondria and in organello gene integration.
AB  - Investigation and manipulation of mitochondrial genetics in animal and plant
      cells remains restricted by the lack of an efficient in vivo transformation
      methodology. Mitochondrial transfection in whole cells and maintenance of the
      transfected DNA are main issues on this track. We showed earlier that isolated
      mitochondria from different organisms can import DNA. Exploiting this mechanism,
      we assessed the possibility to maintain exogenous DNA in plant organelles.
      Whereas homologous recombination is scarce in the higher plant nuclear
      compartment, recombination between large repeats generates the multipartite
      structure of the plant mitochondrial genome. These processes are under strict
      surveillance to avoid extensive genomic rearrangements. Nevertheless, following
      transfection of isolated organelles with constructs composed of a partial gfp
      gene flanked by fragments of mitochondrial DNA, we demonstrated in organello
      homologous recombination of the imported DNA with the resident DNA and
      integration of the reporter gene. Recombination yielded insertion of a continuous
      exogenous DNA fragment including the gfp sequence and at least 0.5 kb of flanking
      sequence on each side. According to our observations, transfection constructs
      carrying multiple sequences homologous to the mitochondrial DNA should be
      suitable and targeting of most regions in the organelle genome should be
      feasible, making the approach of general interest.

PMID- 21715378
TI  - d(CGGTGGT) forms an octameric parallel G-quadruplex via stacking of unusual
      G(:C):G(:C):G(:C):G(:C) octads.
AB  - Among non-canonical DNA secondary structures, G-quadruplexes are currently widely
      studied because of their probable involvement in many pivotal biological roles,
      and for their potential use in nanotechnology. The overall quadruplex scaffold
      can exhibit several morphologies through intramolecular or intermolecular
      organization of G-rich oligodeoxyribonucleic acid strands. In particular, several
      G-rich strands can form higher order assemblies by multimerization between
      several G-quadruplex units. Here, we report on the identification of a novel
      dimerization pathway. Our Nuclear magnetic resonance, circular dichroism, UV, gel
      electrophoresis and mass spectrometry studies on the DNA sequence dCGGTGGT
      demonstrate that this sequence forms an octamer when annealed in presence of K(+)
      or NH(4)(+) ions, through the 5'-5' stacking of two tetramolecular G-quadruplex
      subunits via unusual G(:C):G(:C):G(:C):G(:C) octads.

PMID- 21715379
TI  - Flexible tethering of primase and DNA Pol alpha in the eukaryotic primosome.
AB  - The Pol alpha/primase complex or primosome is the primase/polymerase complex that
      initiates nucleic acid synthesis during eukaryotic replication. Within the
      primosome, the primase synthesizes short RNA primers that undergo limited
      extension by Pol alpha. The resulting RNA-DNA primers are utilized by Pol delta
      and Pol epsilon for processive elongation on the lagging and leading strands,
      respectively. Despite its importance, the mechanism of RNA-DNA primer synthesis
      remains poorly understood. Here, we describe a structural model of the yeast
      primosome based on electron microscopy and functional studies. The 3D
      architecture of the primosome reveals an asymmetric, dumbbell-shaped particle.
      The catalytic centers of primase and Pol alpha reside in separate lobes of high
      relative mobility. The flexible tethering of the primosome lobes increases the
      efficiency of primer transfer between primase and Pol alpha. The physical
      organization of the primosome suggests that a concerted mechanism of primer hand
      off between primase and Pol alpha would involve coordinated movements of the
      primosome lobes. The first three-dimensional map of the eukaryotic primosome at
      25 A resolution provides an essential structural template for understanding
      initiation of eukaryotic replication.

PMID- 21715380
TI  - Exploiting Oxytricha trifallax nanochromosomes to screen for non-coding RNA
      genes.
AB  - We took advantage of the unusual genomic organization of the ciliate Oxytricha
      trifallax to screen for eukaryotic non-coding RNA (ncRNA) genes. Ciliates have
      two types of nuclei: a germ line micronucleus that is usually transcriptionally
      inactive, and a somatic macronucleus that contains a reduced, fragmented and
      rearranged genome that expresses all genes required for growth and asexual
      reproduction. In some ciliates including Oxytricha, the macronuclear genome is
      particularly extreme, consisting of thousands of tiny 'nanochromosomes', each of
      which usually contains only a single gene. Because the organism itself identifies
      and isolates most of its genes on single-gene nanochromosomes, nanochromosome
      structure could facilitate the discovery of unusual genes or gene classes, such
      as ncRNA genes. Using a draft Oxytricha genome assembly and a custom-written
      protein-coding genefinding program, we identified a subset of nanochromosomes
      that lack any detectable protein-coding gene, thereby strongly enriching for
      nanochromosomes that carry ncRNA genes. We found only a small proportion of non
      coding nanochromosomes, suggesting that Oxytricha has few independent ncRNA genes
      besides homologs of already known RNAs. Other than new members of known ncRNA
      classes including C/D and H/ACA snoRNAs, our screen identified one new family of
      small RNA genes, named the Arisong RNAs, which share some of the features of
      small nuclear RNAs.

PMID- 21715382
TI  - ncFANs: a web server for functional annotation of long non-coding RNAs.
AB  - Recent interest in the non-coding transcriptome has resulted in the
      identification of large numbers of long non-coding RNAs (lncRNAs) in mammalian
      genomes, most of which have not been functionally characterized. Computational
      exploration of the potential functions of these lncRNAs will therefore facilitate
      further work in this field of research. We have developed a practical and user
      friendly web interface called ncFANs (non-coding RNA Function ANnotation server),
      which is the first web service for functional annotation of human and mouse
      lncRNAs. On the basis of the re-annotated Affymetrix microarray data, ncFANs
      provides two alternative strategies for lncRNA functional annotation: one
      utilizing three aspects of a coding-non-coding gene co-expression (CNC) network,
      the other identifying condition-related differentially expressed lncRNAs. ncFANs
      introduces a highly efficient way of re-using the abundant pre-existing
      microarray data. The present version of ncFANs includes re-annotated CDF files
      for 10 human and mouse Affymetrix microarrays, and the server will be
      continuously updated with more re-annotated microarray platforms and lncRNA data.
      ncFANs is freely accessible at http://www.ebiomed.org/ncFANs/ or
      http://www.noncode.org/ncFANs/.

PMID- 21715383
TI  - MultiFit: a web server for fitting multiple protein structures into their
      electron microscopy density map.
AB  - Advances in electron microscopy (EM) allow for structure determination of large
      biological assemblies at increasingly higher resolutions. A key step in this
      process is fitting multiple component structures into an EM-derived density map
      of their assembly. Here, we describe a web server for this task. The server takes
      as input a set of protein structures in the PDB format and an EM density map in
      the MRC format. The output is an ensemble of models ranked by their quality of
      fit to the density map. The models can be viewed online or downloaded from the
      website. The service is available at; http://salilab.org/multifit/ and
      http://bioinfo3d.cs.tau.ac.il/.

PMID- 21715384
TI  - RuleGO: a logical rules-based tool for description of gene groups by means of
      Gene Ontology.
AB  - Genome-wide expression profiles obtained with the use of DNA microarray
      technology provide abundance of experimental data on biological and molecular
      processes. Such amount of data need to be further analyzed and interpreted in
      order to obtain biological conclusions on the basis of experimental results. The
      analysis requires a lot of experience and is usually time-consuming process.
      Thus, frequently various annotation databases are used to improve the whole
      process of analysis. Here, we present RuleGO--the web-based application that
      allows the user to describe gene groups on the basis of logical rules that
      include Gene Ontology (GO) terms in their premises. Presented application allows
      obtaining rules that reflect coappearance of GO-terms describing genes supported
      by the rules. The ontology level and number of coappearing GO-terms is adjusted
      in automatic manner. The user limits the space of possible solutions only. The
      RuleGO application is freely available at http://rulego.polsl.pl/.

PMID- 21715385
TI  - The 2011 Bioinformatics Links Directory update: more resources, tools and
      databases and features to empower the bioinformatics community.
AB  - The Bioinformatics Links Directory continues its collaboration with Nucleic Acids
      Research to collaboratively publish and compile a freely accessible, online
      collection of tools, databases and resource materials for bioinformatics and
      molecular biology research. The July 2011 Web Server issue of Nucleic Acids
      Research adds an additional 78 web server tools and 14 updates to the directory
      at http://bioinformatics.ca/links_directory/.

PMID- 21715386
TI  - KOBAS 2.0: a web server for annotation and identification of enriched pathways
      and diseases.
AB  - High-throughput experimental technologies often identify dozens to hundreds of
      genes related to, or changed in, a biological or pathological process. From these
      genes one wants to identify biological pathways that may be involved and diseases
      that may be implicated. Here, we report a web server, KOBAS 2.0, which annotates
      an input set of genes with putative pathways and disease relationships based on
      mapping to genes with known annotations. It allows for both ID mapping and cross
      species sequence similarity mapping. It then performs statistical tests to
      identify statistically significantly enriched pathways and diseases. KOBAS 2.0
      incorporates knowledge across 1327 species from 5 pathway databases (KEGG
      PATHWAY, PID, BioCyc, Reactome and Panther) and 5 human disease databases (OMIM,
      KEGG DISEASE, FunDO, GAD and NHGRI GWAS Catalog). KOBAS 2.0 can be accessed at
      http://kobas.cbi.pku.edu.cn.

PMID- 21715387
TI  - FFAS server: novel features and applications.
AB  - The Fold and Function Assignment System (FFAS) server [Jaroszewski et al. (2005)
      FFAS03: a server for profile-profile sequence alignments. Nucleic Acids Research,
      33, W284-W288] implements the algorithm for protein profile-profile alignment
      introduced originally in [Rychlewski et al. (2000) Comparison of sequence
      profiles. Strategies for structural predictions using sequence information.
      Protein Science: a Publication of the Protein Society, 9, 232-241]. Here, we
      present updates, changes and novel functionality added to the server since 2005
      and discuss its new applications. The sequence database used to calculate
      sequence profiles was enriched by adding sets of publicly available metagenomic
      sequences. The profile of a user's protein can now be compared with ~20
      additional profile databases, including several complete proteomes, human
      proteins involved in genetic diseases and a database of microbial virulence
      factors. A newly developed interface uses a system of tabs, allowing the user to
      navigate multiple results pages, and also includes novel functionality, such as a
      dotplot graph viewer, modeling tools, an improved 3D alignment viewer and links
      to the database of structural similarities. The FFAS server was also optimized
      for speed: running times were reduced by an order of magnitude. The FFAS server,
      http://ffas.godziklab.org, has no log-in requirement, albeit there is an option
      to register and store results in individual, password-protected directories.
      Source code and Linux executables for the FFAS program are available for download
      from the FFAS server.

PMID- 21715388
TI  - inGAP-sv: a novel scheme to identify and visualize structural variation from
      paired end mapping data.
AB  - Mining genetic variation from personal genomes is a crucial step towards
      investigating the relationship between genotype and phenotype. However, compared
      to the detection of SNPs and small indels, characterizing large and particularly
      complex structural variation is much more difficult and less intuitive. In this
      article, we present a new scheme (inGAP-sv) to detect and visualize structural
      variation from paired-end mapping data. Under this scheme, abnormally mapped read
      pairs are clustered based on the location of a gap signature. Several important
      features, including local depth of coverage, mapping quality and associated
      tandem repeat, are used to evaluate the quality of predicted structural
      variation. Compared with other approaches, it can detect many more large
      insertions and complex variants with lower false discovery rate. Moreover, inGAP
      sv, written in Java programming language, provides a user-friendly interface and
      can be performed in multiple operating systems. It can be freely accessed at
      http://ingap.sourceforge.net/.

PMID- 21715389
TI  - RSAT 2011: regulatory sequence analysis tools.
AB  - RSAT (Regulatory Sequence Analysis Tools) comprises a wide collection of modular
      tools for the detection of cis-regulatory elements in genome sequences. Thirteen
      new programs have been added to the 30 described in the 2008 NAR Web Software
      Issue, including an automated sequence retrieval from EnsEMBL (retrieve-ensembl
      seq), two novel motif discovery algorithms (oligo-diff and info-gibbs), a 100
      times faster version of matrix-scan enabling the scanning of genome-scale
      sequence sets, and a series of facilities for random model generation and
      statistical evaluation (random-genome-fragments, random-motifs, random-sites,
      implant-sites, sequence-probability, permute-matrix). Our most recent work also
      focused on motif comparison (compare-matrices) and evaluation of motif quality
      (matrix-quality) by combining theoretical and empirical measures to assess the
      predictive capability of position-specific scoring matrices. To process large
      collections of peak sequences obtained from ChIP-seq or related technologies,
      RSAT provides a new program (peak-motifs) that combines several efficient motif
      discovery algorithms to predict transcription factor binding motifs, match them
      against motif databases and predict their binding sites. Availability (web site,
      stand-alone programs and SOAP/WSDL (Simple Object Access Protocol/Web Services
      Description Language) web services): http://rsat.ulb.ac.be/rsat/.

PMID- 21715390
TI  - Encephalitis in children.
AB  - Encephalitis is an uncommon but potentially devastating neurological syndrome
      with different aetiologies including direct central nervous system infection with
      different agents (most commonly viral) and those mediated by the immune system.
      Whilst there have been several recent publications and guidelines on the
      management of bacterial central nervous system infections in adults and children,
      viral infections have been relatively neglected. Guidelines have been published
      for adults with encephalitis (www.liv.ac.uk/braininfections) but none exist for
      children. For these reasons, we have reviewed the literature on encephalitis and
      have formulated a suggested management strategy for children with suspected,
      clinically diagnosed and proven encephalitis. We have excluded neonates, as
      encephalitis in this age group has different clinical features and is beyond the
      scope of this review.

PMID- 21715391
TI  - PEPtalk: postexposure prophylaxis against varicella in children with cancer.
AB  - OBJECTIVES: To describe postexposure prophylaxis (PEP) against varicella zoster
      virus (VZV) in children being treated for malignancy in the UK and Ireland: the
      population at risk, frequency of exposure, clinical practice and attitudes among
      healthcare providers. DESIGN: An observational study in three parts: (1) a
      retrospective survey of serostatus at diagnosis of malignancy, (2) collation of
      varicella zoster immune globulin (VZIG) dispensing data over a 3-year period and
      (3) an online survey of paediatric oncologists' clinical practice and beliefs in
      relation to VZV disease and its prevention. SETTING: UK and Ireland.
      PARTICIPANTS: Children diagnosed with malignancy in 2009 (serostatus survey) or
      receiving VZIG between April 2006 and March 2009 (VZIG dispensing study).
      Paediatric oncologists and haematologists working in tertiary paediatric oncology
      centres and related shared care units in the UK and Ireland (physician survey).
      RESULTS: Of 1500 children diagnosed with malignancy each year, at least 24% are
      VZV seronegative. Few centres make efforts to prevent household exposure by
      vaccinating VZV-susceptible family members. Exposures to VZV result in the
      administration of PEP to approximately 250 children with cancer annually: half
      receive an intramuscular injection of VZIG while the remainder receive a course
      of oral aciclovir. The choice of PEP is made by doctors. There is no consensus
      among paediatric oncologists as to which is the better option, reflecting the
      lack of a secure evidence base. CONCLUSIONS: A randomised controlled trial to
      compare the effectiveness and acceptability of VZIG and aciclovir as PEP against
      varicella is both desirable and feasible.

PMID- 21715392
TI  - Off-label drug use in children should be rational.

PMID- 21715393
TI  - Treating the wrong children with fluids will cause harm: response to 'mortality
      after fluid bolus in African children with severe infection'.

PMID- 21715394
TI  - Is lenticulostriated vasculopathy a sign of central nervous system insult in
      infants with congenital CMV infection?
AB  - BACKGROUND: In previous studies, lenticulostriated vasculopathy (LSV) was
      detected in 0.4-5.8% of neonates who had undergone brain ultrasound studies
      during the neonatal period. Most infants were referred from neonatal intensive
      care units. Various clinical conditions were associated with LSV including
      intrauterine infections. OBJECTIVE: To investigate whether LSV as a single
      abnormal finding in neonates with congenital cytomegalovirus (CMV) infection is a
      sign of central nervous system (CNS) involvement. METHODS: Ultrasonographic and
      clinical data of all infants with congenital CMV infection, followed in our
      hospital, were collected. All infants with symptomatic congenital CMV infection
      and CNS involvement were treated with ganciclovir for 6 weeks, followed by
      valganciclovir until the age of 1 year. Infants with asymptomatic as well as
      symptomatic infections were followed up with brainstem evoked response and
      behavioural studies every 4 months until 4 years of age. RESULTS: 92 infants
      diagnosed with congenital CMV infection were included in the study. In 50 (54.3%)
      infants, LSV was detected on initial brain ultrasound. Among these patients, 21
      (42%) infants had other ultrasonographic findings consistent with congenital CMV
      infection; 11 (22%) had other symptoms of CNS involvement and in 18 (36%) cases
      the only abnormal finding was LSV. In 9 of the 18 infants with LSV as the only
      finding on initial examination, antiviral therapy was not started. Hearing
      deterioration developed in all nine infants between ages 4 and 34 months.
      Subsequent to these cases, the authors modified their therapy protocol and began
      treating congenital CMV infants with only LSV. 9 infants were treated and all
      maintained normal hearing after 8-27 months of follow-up (p<0.01). CONCLUSIONS:
      LSV is a common finding in infants with symptomatic congenital CMV infection and
      is a sign of CNS involvement. Moreover, LSV is a possible marker of high risk for
      sensorineural hearing loss in infants with congenital CMV infection.

PMID- 21715395
TI  - Vertebrate palaeontology of Australasia into the twenty-first century.
AB  - The 13th Conference on Australasian Vertebrate Evolution Palaeontology and
      Systematics (CAVEPS) took place in Perth, Western Australia, from 27 to 30 April
      2011. This biennial meeting was jointly hosted by Curtin University, the Western
      Australian Museum, Murdoch University and the University of Western Australia.
      Researchers from diverse disciplines addressed many aspects of vertebrate
      evolution, including functional morphology, phylogeny, ecology and extinctions.
      New additions to the fossil record were reported, especially from hitherto under
      represented ages and clades. Yet, application of new techniques in
      palaeobiological analyses dominated, such as dental microwear and geochronology,
      and technological advances, including computed tomography and ancient
      biomolecules. This signals a shift towards increased emphasis in interpreting
      broader evolutionary patterns and processes. Nonetheless, further field
      exploration for new fossils and systematic descriptions will continue to shape
      our understanding of vertebrate evolution in this little-studied, but most
      unusual, part of the globe.

PMID- 21715396
TI  - Noisy human neighbours affect where urban monkeys live.
AB  - Urban areas and many natural habitats are being dominated by a new selection
      pressure: anthropogenic noise. The ongoing expansion of urban areas, roads and
      airports throughout the world makes the noise almost omnipresent. Urbanization
      and the increase of noise levels form a major threat to living conditions in and
      around cities. Insight into the behavioural strategies of urban survivors may
      explain the sensitivity of other species to urban selection pressures. Here, we
      show that urban black-tufted marmosets (Callithrix penicillata) living in noisy
      urban areas may select their home-range based primarily on ambient noise level.
      We have tested the hypothesis that the noise from vehicular traffic and visitors
      in an urban park in Brazil influences the use of home-range (space) by urban
      marmosets. Marmosets even avoided noisy areas with high food availability. In
      addition, they systematically preferred the quieter areas even with dynamic
      changes in the acoustic landscape of the park between weekdays and Sundays (no
      observations were made on Saturdays). These data provide evidence that the use of
      home-range by wild animals can be affected by a potential aversive stimulus such
      as noise pollution.

PMID- 21715397
TI  - Ultraviolet nuptial colour determines fight success in male European green
      lizards (Lacerta viridis).
AB  - Animal communication through colour signals is a central theme in sexual
      selection. Structural colours can be just as costly and honest signals as pigment
      based colours. Ultraviolet (UV) is a structural colour that can be important both
      in intrasexual competition and mate choice. However, it is still unknown if a UV
      signal alone can determine the outcome of male-male fights. European green lizard
      (Lacerta viridis) males develop a nuptial throat coloration with a strong UV
      component. Among males differing only in their manipulated UV colour, females
      prefer males with higher UV. Here, we experimentally decreased the UV coloration
      of randomly chosen males from otherwise similar male pairs to test the hypothesis
      that a difference in UV colour alone can affect fight success during male-male
      competition. Our results fully supported the hypotheses: in almost 90 per cent of
      the contests the male with reduced UV lost the fight. Our results show that UV
      can be an important signal, affecting both female mate choice and determining
      male fight success.

PMID- 21715398
TI  - Happy orang-utans live longer lives.
AB  - Nonhuman primate ageing resembles its human counterpart. Moreover, ratings of
      subjective well-being traits in chimpanzees, orang-utans and rhesus macaques are
      similar to those of humans: they are intercorrelated, heritable, and
      phenotypically and genetically related to personality. We examined whether, as in
      humans, orang-utan subjective well-being was related to longer life. The sample
      included 184 zoo-housed orang-utans followed up for approximately 7 years. Age,
      sex, species and number of transfers were available for all subjects and 172
      subjects were rated on at least one item of a subjective well-being scale. Of the
      31 orang-utans that died, 25 died a mean of 3.4 years after being rated. Even in
      a model that included, and therefore, statistically adjusted for, sex, age,
      species and transfers, orang-utans rated as being "happier" lived longer. The
      risk differential between orang-utans that were one standard deviation above and
      one standard deviation below baseline in subjective well-being was comparable
      with approximately 11 years in age. This finding suggests that impressions of the
      subjective well-being of captive great apes are valid indicators of their welfare
      and longevity.

PMID- 21715399
TI  - Surface wettability of plasma SiOx:H nanocoating-induced endothelial cells'
      migration and the associated FAK-Rho GTPases signalling pathways.
AB  - Vascular endothelial cell (EC) adhesion and migration are essential processes in
      re-endothelialization of implanted biomaterials. There is no clear relationship
      and mechanism between EC adhesion and migration behaviour on surfaces with
      varying wettabilities. As model substrates, plasma SiO(x):H nanocoatings with
      well-controlled surface wettability (with water contact angles in the range of
      98.5 +/- 2.3 degrees  to 26.3 +/- 4.0 degrees ) were used in this study to
      investigate the effects of surface wettability on cell adhesion/migration and
      associated protein expressions in FAK-Rho GTPases signalling pathways. It was
      found that EC adhesion/migration showed opposite behaviour on the hydrophilic and
      hydrophobic surfaces (i.e. hydrophobic surfaces promoted EC migration but were
      anti-adhesions). The number of adherent ECs showed a maximum on hydrophilic
      surfaces, while cells adhered to hydrophobic surfaces exhibited a tendency for
      cell migration. The focal adhesion kinase (FAK) inhibitor targeting the Y-397
      site of FAK could significantly inhibit cell adhesion/migration, suggesting that
      EC adhesion and migration on surfaces with different wettabilities involve (p)FAK
      and its downstream signalling pathways. Western blot results suggested that the
      FAK-Rho GTPases signalling pathways were correlative to EC migration on
      hydrophobic plasma SiO(x):H surfaces, but uncertain to hydrophilic surfaces. This
      work demonstrated that surface wettability could induce cellular behaviours that
      were associated with different cellular signalling events.

PMID- 21715400
TI  - Essential epidemiological mechanisms underpinning the transmission dynamics of
      seasonal influenza.
AB  - Seasonal influenza has considerable impact around the world, both economically
      and in mortality among risk groups, but there is considerable uncertainty as to
      the essential mechanisms and their parametrization. In this paper, we identify a
      number of characteristic features of influenza incidence time series in temperate
      regions, including ranges of annual attack rates and outbreak durations. By
      constraining the output of simple models to match these characteristic features,
      we investigate the role played by population heterogeneity, multiple strains,
      cross-immunity and the rate of strain evolution in the generation of incidence
      time series. Results indicate that an age-structured model with non-random mixing
      and co-circulating strains are both required to match observed time-series data.
      Our work gives estimates of the seasonal peak basic reproduction number, R(0), in
      the range 1.6-3. Estimates of R(0) are strongly correlated with the timescale for
      waning of immunity to current circulating seasonal influenza strain, which we
      estimate is between 3 and 8 years. Seasonal variation in transmissibility is
      largely confined to 15-30% of its mean value. While population heterogeneity and
      cross-immunity are required mechanisms, the degree of heterogeneity and cross
      immunity is not tightly constrained. We discuss our findings in the context of
      other work fitting to seasonal influenza data.

PMID- 21715401
TI  - Complex dynamics of semantic memory access in reading.
AB  - Understanding a word in context relies on a cascade of perceptual and conceptual
      processes, starting with modality-specific input decoding, and leading to the
      unification of the word's meaning into a discourse model. One critical cognitive
      event, turning a sensory stimulus into a meaningful linguistic sign, is the
      access of a semantic representation from memory. Little is known about the
      changes that activating a word's meaning brings about in cortical dynamics. We
      recorded the electroencephalogram (EEG) while participants read sentences that
      could contain a contextually unexpected word, such as 'cold' in 'In July it is
      very cold outside'. We reconstructed trajectories in phase space from single
      trial EEG time series, and we applied three nonlinear measures of predictability
      and complexity to each side of the semantic access boundary, estimated as the
      onset time of the N400 effect evoked by critical words. Relative to controls,
      unexpected words were associated with larger prediction errors preceding the
      onset of the N400. Accessing the meaning of such words produced a phase
      transition to lower entropy states, in which cortical processing becomes more
      predictable and more regular. Our study sheds new light on the dynamics of
      information flow through interfaces between sensory and memory systems during
      language processing.

PMID- 21715402
TI  - Controlling molecular transport through nanopores.
AB  - Nanopores are emerging as powerful tools for the detection and identification of
      macromolecules in aqueous solution. In this review, we discuss the recent
      development of active and passive controls over molecular transport through
      nanopores with emphasis on biosensing applications. We give an overview of the
      solutions developed to enhance the sensitivity and specificity of the resistive
      pulse technique based on biological and solid-state nanopores.

PMID- 21715403
TI  - Temperature alters the photoperiodically controlled phenologies linked with
      migration and reproduction in a night-migratory songbird.
AB  - We investigated the effects of temperature on photoperiodic induction of the
      phenologies linked with migration (body fattening and premigratory night-time
      restlessness, Zugunruhe) and reproduction (testicular maturation) in the
      migratory blackheaded bunting. Birds were exposed for four weeks to near
      threshold photoperiods required to induce testicular growth (11.5 L:12.5 D and 12
      L:12 D) or for 18 weeks to a long photoperiod (13 L:11 D) at 22 degrees C or 27
      degrees C (low) and 35 degrees C or 40 degrees C (high) temperatures. A
      significant body fattening and half-maximal testicular growth occurred in birds
      under the 12 L, but not under the 11.5 L photoperiod. Further, one of six birds
      in both temperature groups on 11.5 L, and four and two of six birds,
      respectively, in low- and high-temperature groups on 12 L showed the Zugunruhe.
      Buntings on 13 L in both temperature groups showed complete growth-regression
      cycles in body fattening, Zugunruhe and testis maturation. In birds on 13 L, high
      temperature attenuated activity levels, delayed onset of Zugunruhe by about 12
      days, reduced body fattening and slowed testicular maturation. The effect of
      temperature seems to be on the rate of photoperiodic induction rather than on the
      critical day length. It is suggested that a change in temperature could alter the
      timing of the development of phenologies linked with seasonal migration and
      reproduction in migratory songbirds.

PMID- 21715404
TI  - Decomposing variation in population growth into contributions from environment
      and phenotypes in an age-structured population.
AB  - Evaluating the relative importance of ecological drivers responsible for natural
      population fluctuations in size is challenging. Longitudinal studies where most
      individuals are monitored from birth to death and where environmental conditions
      are known provide a valuable resource to characterize complex ecological
      interactions. We used a recently developed approach to decompose the observed
      fluctuation in population growth of the red deer population on the Isle of Rum
      into contributions from climate, density and their interaction and to quantify
      their relative importance. We also quantified the contribution of individual
      covariates, including phenotypic and life-history traits, to population growth.
      Fluctuations in composition in age and sex classes ((st)age structure) of the
      population contributed substantially to the population dynamics. Density,
      climate, birth weight and reproductive status contributed less and approximately
      equally to the population growth. Our results support the contention that
      fluctuations in the population's (st)age structure have important consequences
      for population dynamics and underline the importance of including information on
      population composition to understand the effect of human-driven changes on
      population performance of long-lived species.

PMID- 21715405
TI  - Testing the adjustable threshold model for intruder recognition on Myrmica ants
      in the context of a social parasite.
AB  - Social insect colonies are like fortresses, well protected and rich in shared
      stored resources. This makes them ideal targets for exploitation by predators,
      parasites and competitors. Colonies of Myrmica rubra ants are sometimes exploited
      by the parasitic butterfly Maculinea alcon. Maculinea alcon gains access to the
      ants' nests by mimicking their cuticular hydrocarbon recognition cues, which
      allows the parasites to blend in with their host ants. Myrmica rubra may be
      particularly susceptible to exploitation in this fashion as it has large,
      polydomous colonies with many queens and a very viscous population structure. We
      studied the mutual aggressive behaviour of My. rubra colonies based on
      predictions for recognition effectiveness. Three hypotheses were tested: first,
      that aggression increases with distance (geographical, genetic and chemical);
      second, that the more queens present in a colony and therefore the less-related
      workers within a colony, the less aggressively they will behave; and that
      colonies facing parasitism will be more aggressive than colonies experiencing
      less parasite pressure. Our results confirm all these predictions, supporting
      flexible aggression behaviour in Myrmica ants depending on context.

PMID- 21715406
TI  - Rapid changes in phenotype distribution during range expansion in a migratory
      bird.
AB  - The capacity of species to track changing environmental conditions is a key
      component of population and range changes in response to environmental change.
      High levels of local adaptation may constrain expansion into new locations, while
      the relative fitness of dispersing individuals will influence subsequent
      population growth. However, opportunities to explore such processes are rare,
      particularly at scales relevant to species-based conservation strategies.
      Icelandic black-tailed godwits, Limosa limosa islandica, have expanded their
      range throughout Iceland over the last century. We show that current male
      morphology varies strongly in relation to the timing of colonization across
      Iceland, with small males being absent from recently occupied areas. Smaller
      males are also proportionately more abundant on habitats and sites with higher
      breeding success and relative abundance of females. This population-wide spatial
      structuring of male morphology is most likely to result from female preferences
      for small males and better-quality habitats increasing both small-male fitness
      and the dispersal probability of larger males into poorer-quality habitats. Such
      eco-evolutionary feedbacks may be a key driver of rates of population growth and
      range expansion and contraction.

PMID- 21715407
TI  - Variation in memory and the hippocampus across populations from different
      climates: a common garden approach.
AB  - Selection for enhanced cognitive traits is hypothesized to produce enhancements
      to brain structures that support those traits. Although numerous studies suggest
      that this pattern is robust, there are several mechanisms that may produce this
      association. First, cognitive traits and their neural underpinnings may be fixed
      as a result of differential selection on cognitive function within specific
      environments. Second, these relationships may be the product of the selection for
      plasticity, where differences are produced owing to an individual's experiences
      in the environment. Alternatively, the relationship may be a complex function of
      experience, genetics and/or epigenetic effects. Using a well-studied model
      species (black-capped chickadee, Poecile atricapillus), we have for the first
      time, to our knowledge, addressed these hypotheses. We found that differences in
      hippocampal (Hp) neuron number, neurogenesis and spatial memory previously
      observed in wild chickadees persisted in hand-raised birds from the same
      populations, even when birds were raised in an identical environment. These
      findings reject the hypothesis that variation in these traits is owing solely to
      differences in memory-based experiences in different environments. Moreover,
      neuron number and neurogenesis were strikingly similar between captive-raised and
      wild birds from the same populations, further supporting the genetic hypothesis.
      Hp volume, however, did not differ between the captive-raised populations, yet
      was very different in their wild counterparts, supporting the experience
      hypothesis. Our results indicate that the production of some Hp factors may be
      inherited and largely independent of environmental experiences in adult life,
      regardless of their magnitude, in animals under high selection pressure for
      memory, while traits such as volume may be more plastic and modified by the
      environment.

PMID- 21715408
TI  - Social learning spreads knowledge about dangerous humans among American crows.
AB  - Individuals face evolutionary trade-offs between the acquisition of costly but
      accurate information gained firsthand and the use of inexpensive but possibly
      less reliable social information. American crows (Corvus brachyrhynchos) use both
      sources of information to learn the facial features of a dangerous person. We
      exposed wild crows to a novel 'dangerous face' by wearing a unique mask as we
      trapped, banded and released 7-15 birds at five study sites near Seattle, WA,
      USA. An immediate scolding response to the dangerous mask after trapping by
      previously captured crows demonstrates individual learning, while an immediate
      response by crows that were not captured probably represents conditioning to the
      trapping scene by the mob of birds that assembled during the capture. Later
      recognition of dangerous masks by lone crows that were never captured is
      consistent with horizontal social learning. Independent scolding by young crows,
      whose parents had conditioned them to scold the dangerous mask, demonstrates
      vertical social learning. Crows that directly experienced trapping later
      discriminated among dangerous and neutral masks more precisely than did crows
      that learned through social means. Learning enabled scolding to double in
      frequency and spread at least 1.2 km from the place of origin over a 5 year
      period at one site.

PMID- 21715409
TI  - Experimental litter size reduction reveals costs of gestation and delayed effects
      on offspring in a viviparous lizard.
AB  - Experimental studies have often been employed to study costs of reproduction, but
      rarely to study costs of gestation. Disentangling the relative importance of each
      stage of the reproductive cycle should help to assess the costs and benefits of
      different reproductive strategies. To that end, we experimentally reduced litter
      size during gestation in a viviparous lizard. We measured physiological and
      behavioural parameters during gestation and shortly after parturition, as well as
      survival and growth of females and their offspring. This study showed four major
      results. First, the experimental litter size reduction did not significantly
      affect the cellular immune response, the metabolism and the survival of adult
      females. Second, females with reduced litter size decreased their basking time.
      Third, these females also had an increased postpartum body condition. As
      postpartum body condition is positively related to future reproduction, this
      result indicates a gestation cost. Fourth, even though offspring from
      experimentally reduced litters had similar weight and size at birth as other
      offspring, their growth rate after birth was significantly increased. This shows
      the existence of a maternal effect during gestation with delayed consequences.
      This experimental study demonstrates that there are some costs to gestation, but
      it also suggests that some classical trade-offs associated with reproduction may
      not be explained by gestation costs.

PMID- 21715410
TI  - Personal dose equivalent conversion coefficients for electrons to 1 Ge V.
AB  - In a previous paper, conversion coefficients for the personal dose equivalent,
      H(p)(d), for photons were reported. This note reports values for electrons
      calculated using similar techniques. The personal dose equivalent is the quantity
      used to approximate the protection quantity effective dose when performing
      personal dosemeter calibrations and in practice the personal dose equivalent is
      determined using a 30*30*15 cm slab-type phantom. Conversion coefficients to 1
      GeV have been calculated for H(p)(10), H(p)(3) and H(p)(0.07) in the recommended
      slab phantom. Although the conversion coefficients were determined for discrete
      incident energies, analytical fits of the conversion coefficients over the energy
      range are provided using a similar formulation as in the photon results
      previously reported. The conversion coefficients for the personal dose equivalent
      are compared with the appropriate protection quantity, calculated according to
      the recommendations of the latest International Commission on Radiological
      Protection guidance. Effects of eyewear on H(p)(3) are also discussed.

PMID- 21715411
TI  - Use of accelerators in medicine, research, industry, environmental and cultural
      heritage applications.

PMID- 21715412
TI  - A review of some epidemiological studies on cancer risk from low-dose radiation
      or other carcinogenic agents.
AB  - It is extremely difficult to assess cancer risks accurately due to health effects
      of low-dose radiation exposure or other carcinogens based on epidemiological
      studies. For the detection of minute increases of the risk at low-level exposure,
      most of epidemiological studies lack statistical power, and they involve various
      complicated confounding factors. This paper reports on a literature survey of
      epidemiological studies published since 2000 on cancer risks associated with low
      dose radiation and other carcinogens to gather major epidemiological data.
      Integrated risk indices were derived from those data by using, where possible,
      statistical models. Regarding risk assessment of low-dose radiation exposure, it
      is important to lower the degree of uncertainty arising from risk estimation.
      Risk assessment of low-dose radiation exposure could be scientific evidence when
      uncertainty is considered in comparing carcinogenic risks of radiation with those
      of other carcinogens.

PMID- 21715413
TI  - Pharmacological treatment of insomnia in alcohol recovery: a systematic review.
AB  - AIMS: To conduct a systematic review of pharmacological agents used to treat
      sleep problems in alcohol recovery. METHODS: In accordance with the Quorum
      statement, we searched PubMed, EMBASE, Psych Info and Medline databases using the
      terms alcohol, insomnia/sleep and treatment/management with no year/language
      restrictions. RESULTS: The search revealed 1239 articles and 20 met inclusion
      criteria. Trazodone was compared against placebo and found to be superior in two
      trials. Trazodone and gabapentin improved sleep measures with gabapentin
      performing significantly better in an open-label study. The data regarding
      gabapentin are equivocal with few studies showing a clear benefit. In one
      randomized trial, topiramate resulted in improved subjective sleep measures and a
      reduction in the percentage of heavy drinking days. Two randomized control trials
      of carbamazepine revealed improvement in subjective sleep measures. A randomized
      study showed lormetazepam was better than zopiclone on some measures. In a small
      placebo-controlled trial, acamprosate was found to result in improvements on some
      sleep measures. In single, small, mostly open-label studies, quetiapine,
      triazolam, ritanserin, bright light and magnesium have shown efficacy, while
      chlormethiazole, scopolamine and melperone showed no difference or worsening.
      CONCLUSION: Trazodone has the most data suggesting efficacy. This finding is
      tempered by a study suggesting its association with a return to heavy drinking in
      some patients. Data regarding the efficacy of gabapentin are unclear at this
      point.

PMID- 21715414
TI  - The association between social determinants and drunken driving: a 15-year
      register-based study of 81,125 suspects.
AB  - AIMS: The aim of the study was to examine the association between social
      background and drunken driving. METHODS: A Finnish register on suspected drunken
      driving was combined with data on social background. There were 81,125 drivers
      arrested for drunken driving and 86,279 references from 1993 to 2007. RESULTS: A
      low level of education, unemployment, living alone and divorce were strongly
      associated with drunken driving. In addition, for persons aged 15-24 years, low
      parental education and income, high own income and possession of a car correlated
      with higher odds of drunken driving. For working-aged men and women, low income
      was associated with a higher risk of drunken driving. For working-aged women,
      also possession of a car was a risk factor. CONCLUSIONS: Social factors are
      associated with drunken driving. In general, people with a lower social position
      are more prone to drive after drinking. Social differences are visible already in
      youth, whereas working and own income of young persons signal different risk
      mechanisms for youth than for working-aged people. Measures for preventing
      drunken driving are needed within public health policies.

PMID- 21715415
TI  - Ectopic thyroid tissue: anatomical, clinical, and surgical implications of a rare
      entity.
AB  - Ectopic thyroid tissue is a rare entity resulting from developmental defects at
      early stages of thyroid gland embryogenesis, during its passage from the floor of
      the primitive foregut to its final pre-tracheal position. It is frequently found
      around the course of the thyroglossal duct or laterally in the neck, as well as
      in distant places such as the mediastinum and the subdiaphragmatic organs.
      Although most cases are asymptomatic, symptoms related to tumor size and its
      relationship with surrounding tissues may also appear. Any disease affecting the
      thyroid gland may also involve the ectopic thyroid, including malignancy. The
      clinician must distinguish between ectopic thyroid and metastatic deposits
      emerging from an orthotopic gland, as well as other benign or malignant masses.
      Thyroid scintigraphy plays the most important role in diagnosing ectopy, but
      ultrasonography contributes as well. In cases of symptomatic disease, surgery is
      the treatment of choice, followed by radioiodine ablation and levothyroxine
      suppression therapy in more refractory cases. This review provides current
      understanding about the wide clinical spectrum of this rare condition, also
      referring to optimal diagnostic approach, differential diagnosis, and management
      strategies.

PMID- 21715417
TI  - Children whose diet contained olive oil had a lower likelihood of increasing
      their body mass index Z-score over 1 year.
AB  - OBJECTIVE: Changes in eating habits may be influential in the ever-increasing
      rate of childhood obesity. Our aim was to determine whether those children who
      consume olive oil have a lower risk of weight gain compared with children who
      consume other oils. DESIGN AND METHODS: The study included 18 girls and 74 boys,
      all aged 13-166 months. A survey was completed for each subject about eating
      habits and physical activity. A sample of subcutaneous adipose tissue was also
      obtained for cellular study. Data were recorded on the mean size of the
      adipocytes, the number of preadipocytes, and the concentration of particular
      fatty acids. The weight and height of the children were measured 13 months later.
      RESULTS: The likelihood that after 1 year the children would have increased their
      body mass index (BMI) Z-score above the initial score was less in the children
      who consumed only olive oil (odds ratio (OR)=0.22; 95% confidence interval (CI):
      0.08-0.63; P=0.005). These results remained after adjusting for age, physical
      activity and BMI (OR=0.19; 95% CI: 0.06-0.61; P=0.005) and after adjusting for
      age, physical activity and adipocyte volume (OR=0.15; 95% CI: 0.04-0.52;
      P=0.003). CONCLUSIONS: Diets with mono unsaturated fatty acid (MUFA)-rich olive
      oil could reduce the risk of obesity in childhood.

PMID- 21715416
TI  - The European Registry on Cushing's syndrome: 2-year experience. Baseline
      demographic and clinical characteristics.
AB  - OBJECTIVE: The European Registry on Cushing's syndrome (ERCUSYN) is designed to
      collect prospective and follow-up data at EU level on Cushing's syndrome (CS).
      DESIGN AND METHODS: Baseline data on 481 CS patients (390 females, 91 males; mean
      age (+/-s.d.): 44+/-14 years) collected from 36 centres in 23 countries,
      including new patients from 2008 and retrospective cases since 2000. Patients
      were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS)
      (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS)
      (5%) and CS from other aetiologies (2%). RESULTS: Proportion of men in the ECT-CS
      group was higher than in the other groups (P<0.05). The ADR-CS group was older
      than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT
      CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS
      had more skin alterations, menstrual irregularities and hirsutism than ADR-CS
      (P<0.01). Reduced libido was more prevalent in men than women (P<0.01).
      Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males
      had more vertebral and rib fractures than females (52 vs 18% for vertebrae;
      P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more
      frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often
      by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain
      was more common in women than men (P<0.01). CushingQoL and EuroQoL visual
      analogue scale scores did not differ between the groups. CONCLUSIONS: The ERCUSYN
      project demonstrates a heterogeneous clinical presentation of CS at a European
      level, depending on gender and aetiology.

PMID- 21715418
TI  - Long-term outcome of popliteal artery aneurysms after ligation and bypass.
AB  - OBJECTIVES: After exclusion of popliteal artery aneurysms (PAAs) through bypass
      surgery, there is a risk of persistent flow through collaterals and growth of the
      excluded aneurysmal sac. This study was conducted to evaluate this risk at long
      term follow-up. METHODS: Sixty-five PAAs treated by proximal and distal ligation
      and bypass grafting with reversed autologous vein in 52 patients (1998-2010) were
      retrospectively reviewed. RESULTS: Mean follow-up was 41 months (range, 1-144
      months). Five aneurysms showed residual flow (8%). One of these aneurysms had
      increased in size, 36 months postoperatively. This aneurysm underwent an
      embolization procedure after which no flow or further enlargement was
      demonstrated. CONCLUSION: In this study, the risk of persistent flow in a PAA
      excluded by proximal and distal ligation and bypass is low. Still, considering
      this risk and its possible complications, follow-up by duplex ultrasound in all
      patients until up to more than 10 years postoperatively is recommended.

PMID- 21715419
TI  - Noninterruption of warfarin therapy is safe and does not compromise outcome in
      patients undergoing endovenous laser therapy (EVLT).
AB  - OBJECTIVE: To assess the need for cessation of oral anticoagulation with warfarin
      for patients undergoing endovenous laser therapy (EVLT). METHODS: Between
      September 2004 and July 2010, 518 patients underwent 770 EVLT procedures on the
      lower extremity, at our institution. Of these patients, 5 underwent a total of 12
      separate lower extremity EVLT procedures for the treatment of symptomatic reflux
      without interruption of warfarin therapy. RESULTS: No bleeding complications were
      observed during the procedure or in early follow-up. None of the patients
      developed a deep venous thrombosis. Complete ablation of the target vessel was
      observed in all patients on follow-up Duplex ultrasounds at 1 and 8 weeks
      postintervention. CONCLUSION: Endovenous laser therapy can be safely performed
      and does not compromise target vessel ablation in patients receiving oral
      anticoagulation warfarin therapy. Warfarin therapy should not be routinely
      interrupted in patients undergoing this procedure.

PMID- 21715420
TI  - Endovascular repair of traumatic aortic injury using a custom fenestrated
      endograft to preserve the left subclavian artery.
AB  - PURPOSE: To describe the use of custom fenestrated endografts to preserve left
      subclavian artery (SCA) flow when requiring coverage during endovascular repair
      of blunt aortic injury (BAI). CASE REPORT: A 39-year-old male involved in a motor
      vehicle accident sustained injuries including intracranial hemorrhage, BAI, and
      extremity fractures. Immediate neurosurgical intervention was required. Once
      neurologically stabilized, endovascular repair was performed with a commercially
      available device modified with a custom fenestration to preserve flow into the
      left SCA. Serial follow-up CT angiography (CTA) demonstrates satisfactory repair
      with prograde left SCA flow and no evidence of endoleak. CONCLUSION: Left SCA
      coverage is often required for successful endovascular repair of BAI. A subgroup
      of patients who undergo left SCA coverage will require revascularization. The use
      of custom fenestrated endografts for preserving left SCA during thoracic
      endovascular aortic repair (TEVAR) for BAI is an innovative and feasible option
      in patients who require revascularization.

PMID- 21715421
TI  - Azygous collateral thrombosis presenting as ureteric colic.
AB  - A 33 year old man presented to Accident and Emergency with haematuria and
      intermittent left loin pain radiating to the groin. On examination he had
      evidence of lower limb chronic venous insufficiency. Plain abdominal radiograph
      was unremarkable however computed tomography (CT) urogram and subsequent CT of
      thorax/abdomen/pelvis with contrast demonstrated azygous replacement of the
      inferior vena cava with an enlarged azygous vein and multiple enlarged veins in
      the abdomen and pelvis. A 5.7 cm by 4.2 cm low density lesion with surrounding
      inflammatory change was also visualised in the left para-aortic region.
      Ultrasound and magnetic resonance imaging confirmed this as a thrombosed
      collateral of the aberrant venous web drainage. Lifelong anti-coagulation was
      commenced with symptomatic relief.

PMID- 21715422
TI  - External compression of the superior mesenteric artery by the median arcuate
      ligament.
AB  - The median arcuate ligament can compress the proximal portion of the celiac
      artery causing symptoms of chronic mesenteric ischemia. This rare condition
      typically affects young women and often poses a diagnostic challenge. Compression
      of the superior mesenteric artery (SMA) in addition to the celiac artery
      represents an unusual variant of median arcuate ligament syndrome (MALS). We
      present a case of MALS resulting predominantly from external compression of the
      SMA. Diagnostic and therapeutic options are discussed.

PMID- 21715423
TI  - Superior mesenteric vein aneurysm rupture.
AB  - Aneurysmal disease in the venous system is uncommon. The majority of venous
      aneurysms occur in peripheral vessels. Visceral venous aneurysms (VVA) are rare,
      the most common being portal mesenteric vein aneurysms. Because of their rare
      nature, limited information concerning the natural history, presentation, and
      management of VVA is known. Many VVA are asymptomatic; others cause mass effect
      or other complications. Rupture is a rare complication, occurring in only 2.2% of
      VVA. To date, only 17 descriptions of superior mesenteric vein (SMV) aneurysms
      have been reported. We report the first case of a ruptured SMV aneurysm.

PMID- 21715424
TI  - Snail2 controls mesodermal BMP/Wnt induction of neural crest.
AB  - The neural crest is an induced tissue that is unique to vertebrates. In the
      clawed frog Xenopus laevis, neural crest induction depends on signals secreted
      from the prospective dorsolateral mesodermal zone during gastrulation. The
      transcription factors Snail2 (Slug), Snail1 and Twist1 are expressed in this
      region. It is known that Snail2 and Twist1 are required for both mesoderm
      formation and neural crest induction. Using targeted blastomere injection,
      morpholino-based loss of function and explant studies, we show that: (1) Snail1
      is also required for mesoderm and neural crest formation; (2) loss of snail1,
      snail2 or twist1 function in the C2/C3 lineage of 32-cell embryos blocks mesoderm
      formation, but neural crest is lost only in the case of snail2 loss of function;
      (3) snail2 mutant loss of neural crest involves mesoderm-derived secreted factors
      and can be rescued synergistically by bmp4 and wnt8 RNAs; and (4) loss of snail2
      activity leads to changes in the RNA levels of a number of BMP and Wnt agonists
      and antagonists. Taken together, these results identify Snail2 as a key regulator
      of the signals involved in mesodermal induction of neural crest.

PMID- 21715425
TI  - Enhancer-PRE communication contributes to the expansion of gene expression
      domains in proliferating primordia.
AB  - Trithorax-group and Polycomb-group proteins interact with chromosomal elements,
      termed PRE/TREs, to ensure stable heritable maintenance of the transcriptional
      state of nearby genes. Regulatory elements that bind both groups of proteins are
      termed maintenance elements (MEs). Some of these MEs maintain the initial
      activated transcriptional state of a nearby reporter gene through several rounds
      of mitosis during development. Here, we show that expression of hedgehog in the
      posterior compartment of the Drosophila wing results from the communication
      between a previously defined ME and a nearby cis-regulatory element termed the C
      enhancer. The C enhancer integrates the activities of the Notch and Hedgehog
      signalling pathways and, from the early wing primordium stage, drives expression
      to a thin stripe in the posterior compartment that corresponds to the dorsal
      ventral compartment boundary. The ME maintains the initial activated
      transcriptional state conferred by the C enhancer and contributes to the
      expansion, by growth, of its expression domain throughout the posterior
      compartment. Communication between the ME and the C enhancer also contributes to
      repression of gene expression in anterior cells. Most interestingly, we present
      evidence that enhancers and MEs of different genes are interchangeable modules
      whose communication is involved in restricting and expanding the domains of gene
      expression. Our results emphasize the modular role of MEs in regulation of gene
      expression within growing tissues.

PMID- 21715426
TI  - Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo.
AB  - Development of the heart requires recruitment of cardiovascular progenitor cells
      (CPCs) to the future heart-forming region. CPCs are the building blocks of the
      heart, and have the potential to form all the major cardiac lineages. However,
      little is known regarding what regulates CPC fate and behavior. Activity of
      GATA4, SMARCD3 and TBX5 - the 'cardiac BAF' (cBAF) complex, can promote
      myocardial differentiation in embryonic mouse mesoderm. Here, we exploit the
      advantages of the zebrafish embryo to gain mechanistic understanding of cBAF
      activity. Overexpression of smarcd3b and gata5 in zebrafish results in an
      enlarged heart, whereas combinatorial loss of cBAF components inhibits cardiac
      differentiation. In transplantation experiments, cBAF acts cell autonomously to
      promote cardiac fate. Remarkably, cells overexpressing cBAF migrate to the
      developing heart and differentiate as cardiomyocytes, endocardium and smooth
      muscle. This is observed even in host embryos that lack endoderm or cardiac
      mesoderm. Our results reveal an evolutionarily conserved role for cBAF activity
      in cardiac differentiation. Importantly, they demonstrate that Smarcd3b and Gata5
      can induce a primitive, CPC-like state.

PMID- 21715427
TI  - Neuregulins are essential for spermatogonial proliferation and meiotic initiation
      in neonatal mouse testis.
AB  - The transition from mitosis to meiosis is unique to germ cells. In murine
      embryonic ovaries and juvenile testes, retinoic acid (RA) induces meiosis via the
      stimulated by retinoic acid gene 8 (Stra8), but its molecular pathway requires
      elucidation. We present genetic evidence in vivo and in vitro that neuregulins
      (NRGs) are essential for the proliferation of spermatogonia and the initiation of
      meiosis. Tamoxifen (TAM) was injected into 14-day post-partum (dpp) Sertoli cell
      specific conditional Nrg1(Ser-/-) mutant mice. TAM induced testis degeneration,
      suppressed BrdU incorporation into spermatogonia and pre-leptotene primary
      spermatocytes, and decreased and increased the number of STRA8-positive and TUNEL
      positive cells, respectively. In testicular organ cultures from 5-6 dpp wild-type
      mice and cultures of their re-aggregated spermatogonia and Sertoli cells, FSH, RA
      [all-trans-retinoic acid (ATRA), AM580, 9-cis-RA] and NRG1 promoted
      spermatogonial proliferation and meiotic initiation. However, TAM treatment of
      testicular organ cultures from the Nrg1(Ser-/-) mutants suppressed spermatogonial
      proliferation and meiotic initiation that was promoted by FSH or AM580. In re
      aggregated cultures of purified spermatogonia, NRG1, NRG3, ATRA and 9-cis-RA
      promoted their proliferation and meiotic initiation, but neither AM580 nor FSH
      did. In addition, FSH, RAs and NRG1 promoted Nrg1 and Nrg3 mRNA expression in
      Sertoli cells. These results indicate that in juvenile testes RA and FSH induced
      meiosis indirectly through Sertoli cells when NRG1 and NRG3 were upregulated, as
      NRG1 amplified itself and NRG3. The amplified NRG1 and NRG3 directly induced
      meiosis in spermatogonia. In addition, ATRA and 9-cis-RA activated spermatogonia
      directly and promoted their proliferation and eventually meiotic initiation.

PMID- 21715428
TI  - Errors associated with outpatient computerized prescribing systems.
AB  - OBJECTIVE: To report the frequency, types, and causes of errors associated with
      outpatient computer-generated prescriptions, and to develop a framework to
      classify these errors to determine which strategies have greatest potential for
      preventing them. MATERIALS AND METHODS: This is a retrospective cohort study of
      3850 computer-generated prescriptions received by a commercial outpatient
      pharmacy chain across three states over 4 weeks in 2008. A clinician panel
      reviewed the prescriptions using a previously described method to identify and
      classify medication errors. Primary outcomes were the incidence of medication
      errors; potential adverse drug events, defined as errors with potential for harm;
      and rate of prescribing errors by error type and by prescribing system. RESULTS:
      Of 3850 prescriptions, 452 (11.7%) contained 466 total errors, of which 163
      (35.0%) were considered potential adverse drug events. Error rates varied by
      computerized prescribing system, from 5.1% to 37.5%. The most common error was
      omitted information (60.7% of all errors). DISCUSSION: About one in 10 computer
      generated prescriptions included at least one error, of which a third had
      potential for harm. This is consistent with the literature on manual handwritten
      prescription error rates. The number, type, and severity of errors varied by
      computerized prescribing system, suggesting that some systems may be better at
      preventing errors than others. CONCLUSIONS: Implementing a computerized
      prescribing system without comprehensive functionality and processes in place to
      ensure meaningful system use does not decrease medication errors. The authors
      offer targeted recommendations on improving computerized prescribing systems to
      prevent errors.

PMID- 21715429
TI  - The use of count data models in biomedical informatics evaluation research.
AB  - OBJECTIVES: Studies on the impact and value of health information technology
      (HIT) have often focused on outcome measures that are counts of such things as
      hospital admissions or the number of laboratory tests per patient. These measures
      with their highly skewed distributions (high frequency of 0s and 1s) are more
      appropriately analyzed with count data models than the much more frequently used
      variations of ordinary least squares (OLS). Use of a statistical procedure that
      does not properly fit the distribution of the data can result in significant
      findings being overlooked. The objective of this paper is to encourage greater
      use of count data models by demonstrating their utility with an example based on
      the authors' current work. TARGET AUDIENCE: Researchers conducting impact and
      outcome studies related to HIT. SCOPE: We review and discuss count data models
      and illustrate their value in comparison to OLS using an example from a study of
      the impact of an electronic health record (EHR) on laboratory test orders. The
      best count data model reveals significant relationships that OLS does not detect.
      We conclude that comprehensive model checking is highly recommended to identify
      the most appropriate analytic model when the dependent variable being examined
      contains count data. This strategy can lead to more valid and precise findings in
      HIT evaluation studies.

PMID- 21715430
TI  - Diagnosis of pulmonary arteriovenous malformation using a transesophageal
      echocardiography bubble study.

PMID- 21715431
TI  - Orbital fibrosis in a mouse model of Graves' disease induced by genetic
      immunization of thyrotropin receptor cDNA.
AB  - The TSH receptor (TSHR) is the critical target for antibody production in Graves'
      disease (GD). Insulin-like growth factor 1 receptor (IGF1R) has been proposed as
      a second autoantigen in complications of GD such as orbitopathy. We attempted to
      induce orbital tissue remodeling in mice undergoing immunizations with plasmids
      encoding TSHR and IGF1R delivered by in vivo skeletal muscle electroporation, a
      procedure known to give a sustained, long-term antibody response. Female BALB/c
      mice were challenged with TSHR A-subunit or IGF1Ralpha subunit plasmid by
      injection and electroporation. Mice challenged with TSHR A-subunit plasmid
      resulted in high frequency (75%) of hyperthyroidism and thyroid-stimulating
      antibodies. But strikingly, immunization with TSHR A-subunit plasmid also
      elicited antibody to IGF1Ralpha subunit. Mice challenged in the same manner with
      IGF1Ralpha subunit plasmid produced strong antibody responses to IGF1R, but did
      not undergo any changes in phenotype. Simultaneous challenge by double antigen
      immunization with the two plasmids in distant anatomical sites reduced the
      incidence of hyperthyroidism, potentially as a consequence of antigenic
      competition. Thyroid glands from the TSHR A-subunit plasmid-challenged group were
      enlarged with patchy microscopic infiltrates. Histological analysis of the
      orbital tissues demonstrated moderate connective tissue fibrosis and deposition
      of Masson's trichrome staining material. Our findings imply that immunization
      with TSHR A-subunit plasmid leads to generation of IGF1R antibodies, which
      together with thyroid-stimulating antibodies may precipitate remodeling of
      orbital tissue, raising our understanding of its close association with GD.

PMID- 21715432
TI  - Comparison of the effects of the n-3 polyunsaturated fatty acid eicosapentaenoic
      and fenofibrate on the inhibitory effect of arthritis on IGF1.
AB  - Adjuvant-induced arthritis is a chronic inflammatory illness that induces muscle
      wasting and decreases circulating IGF1. Eicosapentaenoic acid (EPA) and
      fenofibrate, a peroxisome proliferator-activated receptors alpha agonist, have
      anti-inflammatory actions and ameliorate muscle wasting in arthritic rats. The
      aim of this work was to elucidate whether EPA and fenofibrate administration are
      able to prevent the effect of arthritis on the IGF1-IGFBP system. On day 4 after
      adjuvant injection control, arthritic rats were gavaged with EPA (1 g/kg) or
      fenofibrate (300 mg/kg) until day 15 when all rats were killed. Arthritis
      decreased body weight gain, serum IGF1, and liver Igf1 mRNA, whereas it increased
      gastrocnemius Igfbp3 mRNA. EPA, but not fenofibrate, administration prevented
      arthritis-induced decrease in serum IGF1 and liver Igf1 mRNA. In the rats treated
      with EPA arthritis increased Igfbp5 mRNA in the gastrocnemius. Fenofibrate
      treatment decreased IGF1 and Igf1 mRNA in the liver and gastrocnemius. In
      arthritic rats, fenofibrate increased body weight gain and decreased
      gastrocnemius Igfbp3 and Igfbp5 mRNA. These data suggest that the mechanisms
      through which EPA and fenofibrate act on the IGF1 system and ameliorate muscle
      wasting in arthritic rats are different. EPA administration increased circulating
      levels of IGF1, whereas fenofibrate decreased the Igfbp3 and Igfbp5 in the
      gastrocnemius muscle.

PMID- 21715433
TI  - The mislabelling of deoxycorticosterone: making sense of corticosteroid structure
      and function.
AB  - Over the 70 or so years since their discovery, there has been continuous interest
      and activity in the field of corticosteroid functions. However, despite major
      advances in the characterisation of receptors and coregulators, in some ways we
      still lack clear insight into the mechanism of receptor activation, and, in
      particular, the relationship between steroid hormone structure and function
      remains obscure. Thus, why should deoxycorticosterone (DOC) reportedly be a weak
      mineralocorticoid, while the addition of an 11beta-hydroxyl group produces
      glucocorticoid activity, yet further hydroxylation at C18 leads to the most
      potent mineralocorticoid, aldosterone? This review aims to show that the field
      has been confused by the misreading of the earlier literature and that DOC, far
      from being relatively inactive, in fact has a wide range of activities not shared
      by the other corticoids. In contrast to the accepted view, the presence of an
      11beta-hydroxyl group yields, in corticosterone or cortisol, hormones with more
      limited functions, and also more readily regulated, by 11beta-hydroxysteroid
      dehydrogenase. This interpretation leads to a more systematic understanding of
      structure-function relationships in the corticosteroids and may assist more
      rational drug design.

PMID- 21715434
TI  - Contemporary activity of colistin and polymyxin B against a worldwide collection
      of Gram-negative pathogens: results from the SENTRY Antimicrobial Surveillance
      Program (2006-09).
AB  - OBJECTIVES: To comparatively evaluate the antimicrobial activities of colistin
      and polymyxin B with those of other antimicrobials against a worldwide collection
      of 40 625 Gram-negative bacilli. METHODS: Antimicrobial susceptibility testing
      was performed and interpreted using the CLSI broth microdilution method except
      for colistin against Enterobacteriaceae. RESULTS: The polymyxins showed potent in
      vitro activities (MIC90, <= 0.5-1 mg/L) against this large collection of clinical
      isolates, with very low resistance rates (< 0.1%-1.5%). Resistance to the
      polymyxins remained stable among organisms tested except for Klebsiella spp.
      isolates collected from the Asia-Pacific and Latin American regions, where a
      trend towards greater resistance was observed (P  <=  0.05). In addition, an
      important reduction in imipenem susceptibility among Acinetobacter spp. and
      Klebsiella spp. was demonstrated in most geographical regions. CONCLUSIONS:
      Although the polymyxins showed excellent in vitro activity against the vast
      majority of Gram-negative bacilli evaluated, a trend to greater resistance was
      observed in the Asia-Pacific and Latin American regions. Therefore, the clinical
      use of polymyxins must be cautious and surveillance monitored.

PMID- 21715435
TI  - Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR)
      polymorphisms are associated with early discontinuation of efavirenz-containing
      regimens.
AB  - OBJECTIVES: Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic
      clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6
      gene are associated with efavirenz pharmacokinetics. Since the constitutive
      androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6
      in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz
      plasma concentrations, we investigated their association with early (<3 months)
      discontinuation of efavirenz therapy. METHODS: Three hundred and seventy-three
      patients initiating therapy with an efavirenz-based regimen were included (278
      white patients and 95 black patients; 293 male). DNA was extracted from whole
      blood and genotyping for CYP2B6 (516G -> T, rs3745274), CAR (540C -> T,
      rs2307424) and PXR (44477T -> C, rs1523130; 63396C -> T, rs2472677; and 69789A ->
      G, rs763645) was conducted. Binary logistic regression using the backwards method
      was employed to assess the influence of SNPs and demographics on early
      discontinuation. RESULTS: Of the 373 patients, 131 withdrew from therapy within
      the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6
      516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking
      status (OR = 0.45; P = 0.002) were associated with discontinuation within 3
      months. CONCLUSIONS: These data indicate that genetic variability in CYP2B6 and
      CAR contributes to early treatment discontinuation for efavirenz-based
      antiretroviral regimens. Further studies are now required to define the clinical
      utility of these associations.

PMID- 21715436
TI  - Evolution of re-emergent virus and its impact on enterovirus 71 epidemics.
AB  - Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae
      family, has become an emergent infectious disease worldwide, most notably in
      Asia. As a neurotropic virus, EV71 infection occasionally causes neurological
      diseases with pulmonary edema, which is fatal for children. In this review, we
      examine the epidemiology of EV71, with three waves of increased EV71 activity
      since the 1970s and discuss the genotypic changes in phylogeny between the
      outbreaks or epidemics. Genetic changes including mutations and recombinations as
      well as the diversity of antigenic properties among EV71 strains in various
      outbreaks are described. Furthermore, the impact of genetic changes on viral
      pathogenesis and vaccine candidate selection are addressed. In conclusion, these
      genetic and antigenic investigations of EV71 evolution have provided us with new
      insight into the trend of EV71 epidemiology, which may contribute to a better
      understanding of the viral pathogenesis and vaccine development.

PMID- 21715437
TI  - The CCR5-delta32 polymorphism as a model to study host adaptation against
      infectious diseases and to develop new treatment strategies.
AB  - Humans respond differently toward exposure against pathogens and some individuals
      are completely resistant against transmission due to a genetically determined
      susceptibility. A rising number of such, so-called, host factors have been
      described during the last years, but their role for diagnostic or therapeutic
      application is still to be clarified. Here, we describe the biology of the
      chemokine receptor CCR5 and its polymorphism in the context of host adaptation
      and immune system function. Furthermore, the first clinical applications
      exploiting our knowledge of this chemokine receptor as a host factor are
      described.

PMID- 21715438
TI  - Crossover studies with survival outcomes.
AB  - Crossover designs are well known to have major advantages when comparing the
      effect of two treatments which do not interact. With a right-censored survival
      endpoint, however, this design is quickly abandoned in favour of the more costly
      parallel design. Motivated by human immunodeficiency virus (HIV) prevention
      studies which lacked power, we evaluate what may be gained in this setting and
      compare parallel with crossover designs. In a heterogeneous population, we find
      and explain a substantial increase in power for the crossover study using a non
      parametric logrank test. With frailties in a proportional hazards model,
      crossover designs equally lead to substantially smaller variance for the subject
      specific hazard ratio (HR), while the population-averaged HR sees negligible
      gain. Its efficiency benefit is recovered when the population-averaged HR is
      reconstructed from estimated subject-specific hazard rates. We derive the time
      point for treatment crossover that optimizes efficiency and end with the analysis
      of two recent HIV prevention trials. We find that a Cellulose sulphate trial
      could have hardly gained efficiency from a crossover design, while a Nonoxynol-9
      trial stood to gain substantial power. We conclude that there is a role for
      effective crossover designs in important classes of survival problems. 

PMID- 21715439
TI  - Physicians' Ethics Forum: a Web-based ethics consultation service.
AB  - To meet all physicians' needs for ethics consultation in Finland, a novel form of
      service, the Physicians' Ethics Forum, was founded in 2003. The Forum is a cost
      efficient service based on electronic communication. In this paper, experiences
      throughout its first 6 years are described.

PMID- 21715440
TI  - Analysis of job strain effects.

PMID- 21715441
TI  - Risk factors and outcomes for patients with vascular disease and serious bleeding
      events.
AB  - OBJECTIVE: To determine the risk and outcomes of serious bleeding events in
      patients with atherosclerotic vascular disease or risk factors. METHODS: 68 375
      outpatients with prior ischaemic vascular events or multiple atherosclerotic risk
      factors were followed in this prospective observational study; 64 977 had 1-year
      follow-up data. Main outcome measures were rates of serious bleeding events and 1
      year outcomes for patients with and without serious bleeding events. RESULTS: The
      1-year rate of serious haemorrhage was 0.92%, with a cerebral haemorrhage rate of
      0.11%. Patients with symptomatic vascular disease had a haemorrhage rate of 1.0%,
      compared with 0.59% in those with risk factors only. Risk factors for serious
      bleeding included age, smoking, hypertension, diabetes, congestive heart failure,
      use of antithrombotics and polyvascular disease. Bleeding risk increased with the
      use of anticoagulants (OR 1.99, 95% CI 1.38 to 2.86, p<0.001) or antiplatelet
      agents combined with anticoagulants (OR 2.54, 95% CI 1.74 to 3.71, p<0.001). By
      logistic regression analysis, patients with a serious bleed (excluding cerebral
      haemorrhage) had a more than threefold increased risk (HR 3.25, 95% CI 2.58 to
      4.10, p<0.0001) of a significant vascular outcome (myocardial infarction, stroke,
      vascular death) compared with patients without a serious bleed. CONCLUSIONS:
      Serious bleeding complications were relatively rare, but significant considering
      the large population at risk. Predictors of increased bleeding were similar to
      the risk factors for ischaemic events. Patients who experienced a serious bleed
      had a significantly higher rate of major vascular events.

PMID- 21715442
TI  - Why is the right ventricular outflow tract so arrhythmogenic? (... or is it
      really?...).

PMID- 21715443
TI  - Cardiovascular MRI in clinical trials: expanded applications through novel
      surrogate endpoints.
AB  - Recent advances in cardiovascular magnetic resonance (CMR) now allow the accurate
      and reproducible measurement of many aspects of cardiac and vascular structure
      and function, with prognostic data emerging for several key imaging biomarkers.
      These biomarkers are increasingly used in the evaluation of new drugs, devices
      and lifestyle modifications for the prevention and treatment of cardiovascular
      disease. This review outlines a conceptual framework for the application of
      imaging biomarkers to clinical trials, highlights several important CMR
      techniques which are in use in randomised studies, and reviews certain aspects of
      trial design, conduct and interpretation in relation to the use of CMR.

PMID- 21715444
TI  - Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia:
      bystander CPR and female gender are predictors of improved outcome. Experiences
      from Sweden in an 18-year perspective.
AB  - OBJECTIVES: In a national perspective, to describe survival among patients found
      in ventricular fibrillation or pulseless ventricular tachycardia witnessed by a
      bystander and with a presumed cardiac aetiology and answer two principal
      questions: (1) what are the changes over time? and (2) which are the factors of
      importance? DESIGN: Observational register study. SETTING: Sweden. PATIENTS: All
      patients included in the Swedish Out of Hospital Cardiac Arrest Register between
      1 January 1990 and 31 December 2009 who were found in bystander-witnessed
      ventricular fibrillation with a presumed cardiac aetiology. Interventions
      Bystander cardiopulmonary resuscitation (CPR) and defibrillation. MAIN OUTCOME
      MEASURES: Survival to 1&emsp14;month. RESULTS: In all, 7187 patients fulfilled
      the set criteria. Age, place of out-of-hospital cardiac arrest (OHCA) and gender
      did not change. Bystander CPR increased from 46% to 73%; 95% CI for OR 1.060 to
      1.081 per year. The median delay from collapse to defibrillation increased from
      12 min to 14 min (p for trend 0.0004). Early survival increased from 28% to 45%
      (95% CI 1.044 to 1.065) and survival to 1 month increased from 12% to 23% (95% CI
      1.058 to 1.086). Strong predictors of early and late survival were a short
      interval from collapse to defibrillation, bystander CPR, female gender and OHCA
      outside the home. CONCLUSION: In a long-term perspective in Sweden, survival to 1
      month after ventricular fibrillation almost doubled. This was associated with a
      marked increase in bystander CPR. Strong predictors of outcome were a short delay
      to defibrillation, bystander CPR, female gender and place of collapse.

PMID- 21715445
TI  - Greenspace in urban neighbourhoods and residents' health: adding quality to
      quantity.
AB  - BACKGROUND: Previous research shows a positive link between the amount of green
      area in one's residential neighbourhood and self-reported health. However, little
      research has been done on the quality of the green area, as well as on quantity
      and quality of smaller natural elements in the streetscape. This study
      investigates the link between the objectively assessed quantity and quality of
      (1) green areas and (2) streetscape greenery on the one hand and three self
      reported health indicators on the other. METHODS: 80 Dutch urban neighbourhoods
      were selected, varying in the amount of nearby green area per dwelling, as
      determined by Geographic Information System analysis. The quality of green areas,
      as well as the quantity and quality of streetscape greenery, was assessed by
      observers using an audit tool. Residents of each neighbourhood were asked to
      complete a questionnaire on their own health (N=1641). In multilevel regression
      analyses, we examined the relationship between greenspace indicators and three
      health indicators, controlling for socio-demographic and socioeconomic
      characteristics. RESULTS: Both indicators for the quantity of greenspace were
      positively related to all three health indicators. Quantity and quality
      indicators were substantially correlated in the case of streetscape greenery.
      Nevertheless, the quality indicators tended to have added predictive value for
      the health indicators, given that the quantity information was already included
      in the model. CONCLUSIONS: The quantity and also the quality of greenspace in
      one's neighbourhood seem relevant with regard to health. Furthermore, streetscape
      greenery is at least as strongly related to self-reported health as green areas.

PMID- 21715446
TI  - Brain natriuretic peptide-guided treatment does not improve morbidity and
      mortality in extensively treated patients with chronic heart failure: responders
      to treatment have a significantly better outcome.
AB  - AIM: To determine whether brain natriuretic peptide (BNP)-guided heart failure
      (HF) treatment improves morbidity and/or mortality when compared with
      conventional treatment. METHODS AND RESULTS: UPSTEP was an investigator
      initiated, randomized, parallel group, multicentre study with a PROBE design.
      Symptomatic patients with worsening HF, New York Heart Association class II-IV,
      ejection fraction <40% and elevated BNP levels, were included. All patients (n=
      279) were treated according to recommended guidelines and randomized to BNP
      guided (BNP) or to conventional (CTR) HF treatment. The goal was to reduce BNP
      levels to <150 ng/L in younger patients and <300 ng/L in elderly patients,
      respectively. The primary outcome was a composite of death due to any cause, need
      for hospitalization and worsening HF. The study groups were well matched,
      including for BNP concentration at entry (mean: 808 vs. 899 ng/L; P= 0.34). There
      were no significant differences between the groups regarding either the primary
      outcome (P = 0.18) or any of the secondary endpoints. There were no differences
      for the pre-specified analyses; days out of hospital, and younger vs. elderly. A
      subgroup analysis comparing treatment responders (>30% decrease in baseline BNP
      value) vs. non-responders found improved survival among responders (P< 0.0001 for
      the primary outcome), and all of the secondary endpoints were also improved.
      CONCLUSIONS: Morbidity and mortality were not improved by HF treatment guided by
      BNP levels. However, BNP responders had a significantly better clinical outcome
      than non-responders. Future research is needed to elucidate the responsible
      pathophysiological mechanisms in this sub-population.

PMID- 21715448
TI  - Non-health-care costs associated with endometriosis.
AB  - BACKGROUND: This study aims to quantify the non-health-care costs of
      endometriosis in a sample of Belgian patients over a 30-month period. METHODS: A
      longitudinal study enrolled patients who underwent surgical treatment for
      endometriosis in University Hospitals Leuven. Self-reported patient
      questionnaires measured costs at 1 month prior to surgical treatment and at 6,
      12, 18 and 24 months following treatment. The number of days of work absence was
      valued using gross monthly income to estimate costs of productivity loss.
      Analysis included patient expenditure on support with household activities. The
      costs per patient over 6 months were obtained by linear extrapolation. RESULTS:
      Of 394 eligible patients, 180 participated in the study (response rate of 46%).
      The highest productivity loss was incurred during the 6 months preceding surgical
      treatment (?1514 +/- 2576) and the 6 months following treatment (?2496 +/- 4144).
      Mean costs dropped to ?115-?225 during the following 6-month periods. Similarly,
      costs of support with household activities peaked during the 6 months preceding
      surgical treatment (?982 +/- 908) and during the subsequent 6 months (?981 +/-
      1085), after which they dropped to ?500-?675 during the following 6-month
      periods. Patients with severe endometriosis (Stage IV) (?4943) had higher total
      non-health-care costs over the 30-month period than patients with minimal-to
      moderate endometriosis (Stages I-III) (?4510) (P = 0.048). CONCLUSIONS: As our
      study did not include a control population of women without endometriosis,
      patients were asked to report non-health-care costs associated with endometriosis
      only. Results show that the highest non-health-care costs associated with
      endometriosis are incurred during the 6 months prior to and following surgical
      treatment.

PMID- 21715447
TI  - Application of the histone deacetylase inhibitors for the treatment of
      endometriosis: histone modifications as pathogenesis and novel therapeutic
      target.
AB  - BACKGROUND: Accumulating evidence suggests that various epigenetic aberrations
      play definite roles in the pathogenesis of endometriosis. We investigated the
      histone acetylation status in endometriosis and the application of the histone
      deacetylase inhibitors (HDACIs) for the treatment of endometriosis. METHODS: The
      levels of acetylated histones in the endometriotic cyst stromal cells (ECSCs) and
      normal endometrial stromal cells (NESCs) were evaluated. The effects of the
      HDACIs on cell proliferation, the cell cycle, apoptosis of ECSCs and NESCs, and
      the expression of genes related to these cellular events were investigated. The
      effects of HDACIs on histone acetylation in chromatin of the promoter region of
      the cell cycle regulatory genes in ECSCs were also investigated. RESULTS: The
      acetylated histone levels were significantly lower in ECSCs than in NESCs (P <
      0.025). HDACIs inhibited cell proliferation and induced cell cycle arrest and
      apoptosis of ECSCs. The effects of HDACIs on NESCs were marginal or weak. These
      HDACIs induced an accumulation of acetylated histones in total cellular chromatin
      and in the promoter regions of the p16(INK4a), p21(Waf1/Cip1), p27(Kip1) and
      cycle checkpoint kinase 2 genes in ECSCs. HDACIs induced the protein expression
      of these cell cycle regulators and suppressed the protein expression of Bcl-2 and
      Bcl-X(L) in ECSCs. CONCLUSIONS: The present findings demonstrated that aberrant
      histone modifications are present in endometriosis and that HDACIs reactivated
      epigenetically silenced genes, resulting in the suppression of cell
      proliferation, induction of cell cycle arrest and apoptosis of ECSCs. HDACIs are
      therefore promising agents for the treatment of endometriosis.

PMID- 21715449
TI  - Ultrastructure and intracellular calcium response during activation in vitrified
      and slow-frozen human oocytes.
AB  - BACKGROUND: The sensitivity of human oocytes to cryodamage may compromise their
      developmental competence following cryopreservation. Herein, we compared the
      ultrastructure and the response to the calcium (Ca2+) ionophore A23187 of fresh,
      slow-frozen and vitrified metaphase II (MII) human oocytes. METHODS:
      Supernumerary fresh MII oocytes, donated under written informed consent, were
      cryopreserved through either a slow cooling procedure based on propane-1,2-diol
      and 0.3 M sucrose or a closed vitrification system based on dimethylsulphoxide
      (DMSO) and ethylene glycol (EG). Ultrastructure of fresh and cryopreserved
      oocytes was assessed by transmission electron microscopy and compared through
      morphometrical analysis; intracellular calcium ([Ca2+](i)) dynamics was studied
      by evaluating the response to the Ca2+ ionophore A23187. RESULTS: Morphometric
      analysis demonstrated a markedly higher proportion of oocytes with large
      vacuoles, inward displacement of organelles from the pericortical toward the deep
      cytoplasm, and mitochondrial damage in slow-frozen compared with both fresh and
      vitrified oocytes. A23187 increased the [Ca2+](i) in all oocyte groups and the
      peak average increase in slow-frozen oocytes was significantly higher than in
      both fresh and vitrified oocytes. Moreover, the ability of slow-frozen oocytes to
      recover [Ca2+](i) to basal levels was significantly reduced compared with both
      fresh and vitrified oocytes. CONCLUSIONS: Closed vitrification based on DMSO and
      EG preserves the ultrastructural features and the ability to respond to the Ca2+
      ionophore A23187 significantly better than does slow freezing with 0.3 M sucrose.
      Damage to organelles involved in the [Ca2+](i) modulation might reduce the
      developmental competence of cryopreserved oocytes.

PMID- 21715450
TI  - Crossing borders for fertility treatment: motivations, destinations and outcomes
      of UK fertility travellers.
AB  - BACKGROUND: There are few systematic studies of the incidence of cross-border
      fertility care and even fewer reports of qualitative research with those
      undertaking treatment outside their country of origin. This paper reports
      findings from a qualitative study of UK residents with experience of cross-border
      care: the socio-demographic characteristics of UK travellers; their reasons for
      seeking treatment abroad; the treatments they sought; the destinations they chose
      and the outcomes of their treatment. METHODS: Data regarding cross-border
      fertility treatment were collected from a purposive sample of 51 people by means
      of in-depth, semi-structured interviews between May 2009 and June 2010. Data were
      analysed using a systematic thematic coding method and also subjected to
      quantitative translation. RESULTS: Patient motivations for travelling abroad are
      complex. A desire for timely and affordable treatment with donor gametes was
      evident in a high number of cases (71%). However, most people gave several
      reasons, including: the cost of UK treatment; higher success rates abroad;
      treatment in a less stressful environment and dissatisfaction with UK treatment.
      People travelled to 13 different countries, the most popular being Spain and the
      Czech Republic. Most organized their own treatment and travel. The mean age of
      women seeking treatment was 38.8 years (range 29-46 years) and the multiple
      pregnancy rate was 19%. CONCLUSIONS: UK residents have diverse reasons for, and
      approaches to, seeking overseas treatment and do not conform to media
      stereotypes. Further research is needed to explore implications of cross-border
      treatment for donors, offspring and healthcare systems.

PMID- 21715451
TI  - IVF and endometriosis-related symptom progression: insights from a prospective
      study.
AB  - BACKGROUND: A possible and neglected concern in women with endometriosis
      undergoing IVF is the potential risk of progression of the disease. We set up a
      prospective study mainly aimed at evaluating the impact of IVF on endometriosis
      related symptoms. MATERIALS AND METHODS: Women with surgical or echographic
      diagnosis of endometriosis and selected for IVF were included. In the month
      preceding the IVF attempt and at a second evaluation 3-6 months after the cycle,
      women who did not get pregnant underwent clinical assessment and transvaginal
      ultrasonography. Each patient was requested to complete a questionnaire on the
      presence, severity and modifications of endometriosis-related symptoms before and
      after the IVF cycle. RESULTS: Overall, 64 patients completed the study protocol.
      The Biberoglu-Behrman Scores and the Verbal Rate Scales for dysmenorrhea,
      dispareunia and chronic pelvic pain did not worsen after the procedure. Other
      endometriosis-related symptoms also did not change. There was no modification in
      size and number of endometriomas and deep peritoneal nodules. The number (%) of
      women reporting general improvement and worsening were 14 (22%) and 7 (11%),
      respectively. CONCLUSIONS: IVF does not expose women to a consistent risk of
      endometriosis-related symptoms progression.

PMID- 21715452
TI  - Jaundiced after a party.

PMID- 21715453
TI  - Deaths from chronic disease fall in Australia but concerns rise for the future.

PMID- 21715454
TI  - BMA meeting: BMA rejects attempt to lower upper time limit for abortion.

PMID- 21715455
TI  - BMA meeting: BMA reaffirms its policy of "soft consent" on organ transplantation.

PMID- 21715456
TI  - We should publish the cost of each piece of research.

PMID- 21715457
TI  - Death of the silent witness: patients' reporting of adverse drug reactions.

PMID- 21715458
TI  - US court rules that patients harmed by generic drugs cannot claim damages.

PMID- 21715459
TI  - The error of our ways.

PMID- 21715460
TI  - BMA meeting: GPs are being told to limit their hospital referrals, meeting hears.

PMID- 21715461
TI  - European drug agency extends review of safety of pioglitazone.

PMID- 21715462
TI  - FDA seeks global partners to improve safety of imported food, medicines, and
      devices.

PMID- 21715463
TI  - BMA meeting: BMA refuses to reject health bill "in its entirety".

PMID- 21715464
TI  - A woman with episodic headaches, sweating, and palpitations.

PMID- 21715465
TI  - Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels
      across dementia staging in Alzheimer's disease: a clinical setting-based
      retrospective study.
AB  - We examined retrospectively the concurrent relationships between fasting plasma
      total cholesterol, triglycerides, and glucose levels, and Alzheimer's disease
      (AD), in a clinical setting-based study. Total cholesterol level was higher in
      patients with AD compared to elderly controls; triglycerides or glucose levels
      did not significantly differ between the 2 groups. Respective plotted
      trajectories of change in cholesterol level across age were fairly parallel. No
      significant difference in total cholesterol levels was recorded between patients
      with AD classified by the Clinical Dementia Rating (CDR) score subgroups. These
      results suggest that patients with AD have relative mild total
      hypercholesterolemia, normal triglyceridemia, and normal fasting plasma glucose
      level. Mild total hypercholesterolemia seems to be permanent across age, and
      across dementia severity staging, and fairly parallels the trajectory of age
      related change in total cholesterolemia of healthy controls. We speculate that
      these biochemical parameters pattern may be present long before-a decade at least
      the symptomatic onset of the disease.

PMID- 21715466
TI  - Mining small-molecule screens to repurpose drugs.
AB  - Repurposing and repositioning drugs--discovering new uses for existing and
      experimental medicines-is an attractive strategy for rescuing stalled
      pharmaceutical projects, finding treatments for neglected diseases, and reducing
      the time, cost and risk of drug development. As this strategy emerged, academic
      researchers began performing high-throughput screens (HTS) of small molecules-
      the type of experiments once exclusively conducted in industry--and making the
      data from these screens available to all. Several methods can mine this data to
      inform repurposing and repositioning efforts. Despite these methods' limitations,
      it is hopeful that they will accelerate the discovery of new uses for known
      drugs, but this hope has not yet been realized.

PMID- 21715467
TI  - Improving the prediction of disulfide bonds in Eukaryotes with machine learning
      methods and protein subcellular localization.
AB  - MOTIVATION: Disulfide bonds stabilize protein structures and play relevant roles
      in their functions. Their formation requires an oxidizing environment and their
      stability is consequently depending on the redox ambient potential, which may
      differ according to the subcellular compartment. Several methods are available to
      predict cysteine-bonding state and connectivity patterns. However, none of them
      takes into consideration the relevance of protein subcellular localization.
      RESULTS: Here we develop DISLOCATE, a two-step method based on machine learning
      models for predicting both the bonding state and the connectivity patterns of
      cysteine residues in a protein chain. We find that the inclusion of protein
      subcellular localization improves the performance of these predictive steps by 3
      and 2 percentage points, respectively. When compared with previously developed
      methods for predicting disulfide bonds from sequence, DISLOCATE improves the
      overall performance by more than 10 percentage points. AVAILABILITY: The method
      and the dataset are available at the Web page
      http://www.biocomp.unibo.it/savojard/Dislocate.html. GRHCRF code is available at
      http://www.biocomp.unibo.it/savojard/biocrf.html. CONTACT:
      piero.fariselli@unibo.it.

PMID- 21715468
TI  - Measuring vaccination coverage in a hard to reach minority.
AB  - BACKGROUND: Although childhood vaccination programmes have been very successful,
      there are some hard to reach minority groups that object to vaccination. The
      Netherlands has experienced several epidemics of vaccine-preventable diseases,
      confined to the orthodox Protestant minority. However, vaccination coverage in
      this minority is still unknown and this hampers prevention and control of
      epidemics. METHODS: We estimated vaccination coverage among the orthodox
      Protestant minority and its various subgroups (denominations), using two sub
      studies with different design and study population. For both sub-studies
      separately, we determined overall vaccination coverage and vaccination coverage
      per denomination. The results were compared and discussed. RESULTS: An online
      survey was filled out by 1778 orthodox Protestant youngsters, invited via
      orthodox Protestant media using a snowball method. Next to that, results of a
      national sample study on vaccination were used, of which only orthodox Protestant
      respondents were included in our analyses (N  =  2129). Overall vaccination
      coverage among orthodox Protestants in The Netherlands was estimated to be at
      minimum 60%. Moreover, in both sub-studies three clusters of denominations could
      be identified, with high (>85%), intermediate (50-75%) and low (<25%) vaccination
      coverage. CONCLUSION: The integration of both sub-studies, with their own
      specific strengths and weaknesses, added to our insight in the vaccination
      coverage in this minority. Based on these results, we recommend to focus
      prevention and control of vaccine-preventable diseases on the orthodox Protestant
      subgroups with intermediate and low vaccination coverage.

PMID- 21715469
TI  - Fat-free mass predictions through a Bayesian Network enable body composition
      comparisons in various populations.
AB  - The respective contribution of fat-free mass (FFM) and fat mass to body weight
      (Wgt) is a relevant indicator of risk for major public health issues. In an
      earlier study, a Bayesian Network (BN) was designed to predict FFM from a DXA
      database (1999-2004 NHANES, n = 10,402) with easily accessible variables [sex,
      age, Wgt, and height (Hgt)]. The objective of the present study was to assess the
      robustness of these BN predictions in different population contexts (age, BMI,
      ethnicity, etc.) when covariables were stochastically deduced from population
      based distributions. BN covariables were adjusted to 82 published distributions
      for age, Wgt, and Hgt from 16 studies assessing body composition. Anthropometric
      adjustments required a surrogate database (n = 23,411) to get the missing
      correlation between published Wgt and Hgt distributions. Published BMI
      distributions and their predicted BN counterparts were correlated (R(2) = 0.99; P
      < 0.001). Predicted FFM distributions were closely adjusted to their published
      counterparts for both sexes between 20 and 79 y old, with some discrepancies for
      Asian populations. In addition, BN predictions revealed a very good agreement
      between FFM assessed in different population contexts. The mean difference
      between published FFM values (61.1 +/- 3.44 and 42.7 +/- 3.32 kg for men and
      women, respectively) and BN predictions (61.6 +/- 3.11 and 42.4 +/- 2.76 kg for
      men and women, respectively) was <1% when FFM was assessed by DXA; the difference
      rose to 3.6% when FFM was assessed by bioelectric impedance analysis or by
      densitometry methods. These results suggest that it is possible, within certain
      anthropometric limitations, to use BN predictions as a complementary body
      composition analysis for large populations.

PMID- 21715470
TI  - Quantitation of [5-14CH3]-(2R, 4'R, 8'R)-alpha-tocopherol in humans.
AB  - Half-lives of alpha-tocopherol in plasma have been reported as 2-3 d, whereas the
      Elgin Study required >2 y to deplete alpha-tocopherol, so gaps exist in our
      quantitative understanding of human alpha-tocopherol metabolism. Therefore, 6 men
      and 6 women aged 27 +/- 6 y (mean +/- SD) ingested 1.81 nmol, 3.70 kBq of [5
      (14)CH(3)]-(2R, 4'R, 8'R)-alpha-tocopherol. The levels of (14)C in blood plasma
      and washed RBC were monitored frequently from 0 to 460 d while the levels of
      (14)C in urine and feces were monitored from 0 to 21 d. Total fecal elimination
      (fecal + metabolic fecal) was 23.24 +/- 5.81% of the (14)C dose, so feces over
      urine was the major route of elimination of the ingested [5-(14)CH(3)]-(2R, 4'R,
      8'R)-alpha-tocopherol, consistent with prior estimates. The half-life of alpha
      tocopherol varied in plasma and RBC according to the duration of study. The
      minute dose coupled with frequent monitoring over 460 d and 21 d for blood,
      urine, and feces ensured the [5-(14)CH(3)]-(2R, 4'R, 8'R)-alpha-tocopherol (the
      tracer) had the chance to fully mix with the endogenous [5-(14)CH(3)]-(2R, 4'R,
      8'R)-alpha-tocopherol (the tracee). The (14)C levels in neither plasma nor RBC
      had returned to baseline by d 460, indicating that the t(1/2) of [5-CH(3)]-(2R,
      4'R, 8'R)-alpha-tocopherol in human blood was longer than prior estimates.

PMID- 21715472
TI  - Retraction. Spirolactone prevents renal dysfunction and fibrosis induced by
      tacrolimus.

PMID- 21715471
TI  - Regulation of renal NaCl and water transport by the ATP/UTP/P2Y2 receptor system.
AB  - Extracellular nucleotides (e.g., ATP) activate ionotropic P2X and metabotropic
      P2Y receptors in the plasma membrane to regulate and maintain cell function and
      integrity. This includes the renal tubular and collecting duct system, where the
      locally released nucleotides act in a paracrine and autocrine way to regulate
      transport of electrolytes and water and maintain cell volume. A prominent role
      has been assigned to Gq-coupled P2Y(2) receptors, which are typically activated
      by both ATP and UTP. Studies in gene knockout mice revealed an antihypertensive
      activity of P2Y(2) receptors that is linked to vasodilation and an inhibitory
      influence on renal salt reabsorption. Flow induces apical ATP release in the
      thick ascending limb, and first evidence indicates an inhibitory influence of
      P2Y(2) receptor tone on the expression and activity of the Na-K-2Cl cotransporter
      NKCC2 in this segment. The apical ATP/UTP/P2Y(2) receptor system in the
      connecting tubule/cortical collecting duct mediates the inhibitory effect of
      dietary salt on the open probability of the epithelial sodium channel ENaC and
      inhibits ENaC activity during aldosterone escape. Connexin 30 has been implicated
      in the luminal release of the ATP involved in the regulation of ENaC. An increase
      in collecting duct cell volume in response to manipulating water homeostasis
      increases ATP release. The subsequent activation of P2Y(2) receptors inhibits
      vasopressin-induced cAMP formation and water reabsorption, which facilitates
      water excretion and stabilizes cell volume. Thus recent studies have established
      the ATP/UTP/P2Y(2) receptor system as a relevant regulator of renal salt and
      water homeostasis and blood pressure regulation. The pathophysiological relevance
      and therapeutic potential remains to be determined, but dual effects of P2Y(2)
      receptor activation on both the vasculature and renal salt reabsorption implicate
      these receptors as potential therapeutic targets in hypertension.

PMID- 21715473
TI  - p63 is necessary for the activation of human papillomavirus late viral functions
      upon epithelial differentiation.
AB  - The late phase of the human papillomavirus (HPV) life cycle is linked to
      epithelial differentiation, and we investigated the factors that regulate this
      process. One potential regulator is p63, a member of the p53 family of proteins,
      which modulates epithelial development, as well as proliferation capability, in
      stem cells. In this study, we examined the role of p63 in the HPV life cycle
      using a lentiviral knockdown system for p63. In epithelial cells, the DeltaN
      truncated isoforms of p63 predominate, while the full-length TA isoforms are
      present at very low levels. Upon the differentiation of normal keratinocytes, p63
      levels rapidly decreased while higher levels were retained in HPV-positive cells.
      Our studies indicate that reducing p63 levels in differentiated HPV-positive
      cells resulted in the loss of viral genome amplification and late gene
      expression. p63 regulates the expression of cell cycle regulators, and we
      determined that cyclin A, cyclin B1, cdk1, and cdc25c were reduced in p63
      deficient, HPV-positive keratinocytes, which suggests a possible mechanism of
      action. In addition, activation of the DNA repair pathway is necessary for genome
      amplification, and the expression of two members, BRCA2 and RAD51, was altered in
      the absence of p63 in HPV-positive cells. Our studies indicate that p63 is
      necessary for the activation of differentiation-dependent HPV late viral
      functions and provide insights into relevant cellular targets.

PMID- 21715474
TI  - The cytoplasmic domain of rhesus cytomegalovirus Rh178 interrupts translation of
      major histocompatibility class I leader peptide-containing proteins prior to
      translocation.
AB  - Cytomegalovirus (CMV) efficiently evades many host immune defenses and encodes a
      number of proteins that prevent antigen presentation by major histocompatibility
      complex class I (MHC-I) molecules in order to evade recognition and killing of
      infected cells by cytotoxic CD8(+) T cells. We recently showed that rhesus CMV
      specific Rh178 intercepts MHC-I protein translation before interference of MHC-I
      maturation by homologues of the human CMV US6 family. Here, we demonstrate that
      Rh178 localizes to the membrane of the endoplasmic reticulum, displaying a short
      luminal and large cytosolic domain, and that the membrane-proximal cytosolic
      portion is essential for inhibition of MHC-I expression. We further observed that
      Rh178 does not require synthesis of full-length MHC-I heavy chains but is capable
      of inhibiting the translation of short, unstable amino-terminal fragments of MHC
      I. Moreover, the transfer of amino-terminal fragments containing the MHC-I signal
      peptide renders recipient proteins susceptible to targeting by Rh178. The
      cytosolic orientation of Rh178 and its ability to target protein fragments
      carrying the MHC-I signal peptide are consistent with Rh178 intercepting
      partially translated MHC-I heavy chains after signal recognition particle
      dependent transfer to the endoplasmic reticulum membrane. However, interference
      with MHC-I translation by Rh178 seems to occur prior to SEC61-dependent protein
      translocation, since inhibition of MHC-I translocation by eeyarestatin 1 resulted
      in a full-length degradation intermediate that can be stabilized by proteasome
      inhibitors. These data are consistent with Rh178 blocking protein translation of
      MHC-I heavy chains at a step prior to the start of translocation, thereby
      downregulating MHC-I at a very early stage of translation.

PMID- 21715475
TI  - Prototype foamy virus gag nuclear localization: a novel pathway among
      retroviruses.
AB  - Gag nuclear localization has long been recognized as a hallmark of foamy virus
      (FV) infection. Two required motifs, a chromatin-binding site (CBS) and a nuclear
      localization signal (NLS), both located in glycine-arginine-rich box II (GRII),
      have been described. However, the underlying mechanisms of Gag nuclear
      translocation are largely unknown. We analyzed prototype FV (PFV) Gag nuclear
      localization using a novel live-cell fluorescence microscopy assay. Furthermore,
      we characterized the nuclear localization route of Gag mutants tagged with the
      simian vacuolating virus 40-NLS (SV40-NLS) and also dissected the respective
      contributions of the CBS and the NLS. We found that PFV Gag does not translocate
      to the nucleus of interphase cells by NLS-mediated nuclear import and does not
      possess a functional NLS. PFV Gag nuclear localization occurred only by tethering
      to chromatin during mitosis. This mechanism was found for endogenously expressed
      Gag as well as for Gag delivered by infecting viral particles. Thereby, the CBS
      was absolutely essential, while the NLS was dispensable. Gag CBS-dependent
      nuclear localization was neither essential for infectivity nor necessary for Pol
      encapsidation. Interestingly, Gag localization was independent of the presence of
      Pol, Env, and viral RNA. The addition of a heterologous SV40-NLS resulted in the
      nuclear import of PFV Gag in interphase cells, rescued the nuclear localization
      deficiency but not the infectivity defect of a PFV Gag DeltaGRII mutant, and did
      not enhance FV's ability to infect G(1)/S-phase-arrested cells. Thus, PFV Gag
      nuclear localization follows a novel pathway among orthoretroviral Gag proteins.

PMID- 21715476
TI  - Glyceraldehyde 3-phosphate dehydrogenase negatively regulates the replication of
      Bamboo mosaic virus and its associated satellite RNA.
AB  - The identification of cellular proteins associated with virus replicase complexes
      is crucial to our understanding of virus-host interactions, influencing the host
      range, replication, and virulence of viruses. A previous in vitro study has
      demonstrated that partially purified Bamboo mosaic virus (BaMV) replicase
      complexes can be employed for the replication of both BaMV genomic and satellite
      BaMV (satBaMV) RNAs. In this study, we investigated the BaMV and satBaMV 3'
      untranslated region (UTR) binding proteins associated with these replicase
      complexes. Two cellular proteins with molecular masses of ~35 and ~55 kDa were
      specifically cross-linked with RNA elements, whereupon the ~35-kDa protein was
      identified as the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH). Gel mobility shift assays confirmed the direct interaction of GAPDH with
      the 3' UTR sequences, and competition gel shift analysis revealed that GAPDH
      binds preferentially to the positive-strand BaMV and satBaMV RNAs over the
      negative-strand RNAs. It was observed that the GAPDH protein binds to the
      pseudoknot poly(A) tail of BaMV and stem-loop-C poly(A) tail of satBaMV 3' UTR
      RNAs. It is important to note that knockdown of GAPDH in Nicotiana benthamiana
      enhances the accumulation of BaMV and satBaMV RNA; conversely, transient
      overexpression of GAPDH reduces the accumulation of BaMV and satBaMV RNA. The
      recombinant GAPDH principally inhibits the synthesis of negative-strand RNA in
      exogenous RdRp assays. These observations support the contention that cytosolic
      GAPDH participates in the negative regulation of BaMV and satBaMV RNA
      replication.

PMID- 21715477
TI  - Reconstructing the history of maize streak virus strain a dispersal to reveal
      diversification hot spots and its origin in southern Africa.
AB  - Maize streak virus strain A (MSV-A), the causal agent of maize streak disease, is
      today one of the most serious biotic threats to African food security.
      Determining where MSV-A originated and how it spread transcontinentally could
      yield valuable insights into its historical emergence as a crop pathogen.
      Similarly, determining where the major extant MSV-A lineages arose could identify
      geographical hot spots of MSV evolution. Here, we use model-based phylogeographic
      analyses of 353 fully sequenced MSV-A isolates to reconstruct a plausible history
      of MSV-A movements over the past 150 years. We show that since the probable
      emergence of MSV-A in southern Africa around 1863, the virus spread
      transcontinentally at an average rate of 32.5 km/year (95% highest probability
      density interval, 15.6 to 51.6 km/year). Using distinctive patterns of nucleotide
      variation caused by 20 unique intra-MSV-A recombination events, we tentatively
      classified the MSV-A isolates into 24 easily discernible lineages. Despite many
      of these lineages displaying distinct geographical distributions, it is apparent
      that almost all have emerged within the past 4 decades from either southern or
      east-central Africa. Collectively, our results suggest that regular analysis of
      MSV-A genomes within these diversification hot spots could be used to monitor the
      emergence of future MSV-A lineages that could affect maize cultivation in Africa.

PMID- 21715478
TI  - The herpes simplex virus 1 latency-associated transcript promotes functional
      exhaustion of virus-specific CD8+ T cells in latently infected trigeminal
      ganglia: a novel immune evasion mechanism.
AB  - Following ocular herpes simplex virus 1 (HSV-1) infection of C57BL/6 mice, HSV
      specific (HSV-gB(498-505) tetramer(+)) CD8(+) T cells are induced, selectively
      retained in latently infected trigeminal ganglia (TG), and appear to decrease HSV
      1 reactivation. The HSV-1 latency-associated transcript (LAT) gene, the only
      viral gene that is abundantly transcribed during latency, increases reactivation.
      Previously we found that during latency with HSV-1 strain McKrae-derived viruses,
      more of the total TG resident CD8 T cells expressed markers of exhaustion with
      LAT(+) virus compared to LAT(-) virus. Here we extend these findings to HSV-1
      strain 17syn+-derived LAT(+) and LAT(-) viruses and to a virus expressing just
      the first 20% of LAT. Thus, the previous findings were not an artifact of HSV-1
      strain McKrae, and the LAT function involved mapped to the first 1.5 kb of LAT.
      Importantly, to our knowledge, we show here for the first time that during LAT(+)
      virus latency, most of the HSV-1-specific TG resident CD8 T cells were
      functionally exhausted, as judged by low cytotoxic function and decreased gamma
      interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) production.
      This resulted in LAT(-) TG having more functional HSV-gB(498-505) tetramer(+)
      CD8(+) T cells compared to LAT(+) TG. In addition, LAT expression, in the absence
      of other HSV-1 gene products, appeared to be able to directly or indirectly
      upregulate both PD-L1 and major histocompatibility complex class I (MHC-I) on
      mouse neuroblastoma cells (Neuro2A). These findings may constitute a novel immune
      evasion mechanism whereby the HSV-1 LAT directly or indirectly promotes
      functional exhaustion (i.e., dysfunction) of HSV-specific CD8(+) T cells in
      latently infected TG, resulting in increased virus reactivation.

PMID- 21715479
TI  - Gene N proximal and distal RNA motifs regulate coronavirus nucleocapsid mRNA
      transcription.
AB  - Coronavirus subgenomic mRNA (sgmRNA) transcription requires a discontinuous RNA
      synthesis mechanism driven by the transcription-regulating sequences (TRSs),
      located at the 3' end of the genomic leader (TRS-L) and also preceding each gene
      (TRS-B). In transmissible gastroenteritis virus (TGEV), the free energy of TRS-L
      and cTRS-B (complement of TRS-B) duplex formation is one of the factors
      regulating the transcription of sgmRNAs. In addition, N gene sgmRNA transcription
      is controlled by a transcription-regulating motif, including a long-distance RNA
      RNA interaction between complementary proximal and distal elements. The extension
      of complementarity between these two sequences increased N gene transcription. An
      active domain, a novel essential component of the transcription-regulating motif,
      has been identified. The active domain primary sequence was necessary for its
      activity. Relocation of the active domain upstream of the N gene TRS core
      sequence in the absence of the proximal and distal elements also enhanced sgmRNA
      N transcription. According to the proposed working model for N gene
      transcriptional activation, the long-distance RNA-RNA interaction relocates the
      distant active domain in close proximity with the N gene TRS, which probably
      increases the frequency of template switching during the synthesis of negative
      RNA. The transcription-regulating motif has been optimized to a minimal sequence
      showing a 4-fold activity increase in relation to the native RNA motif. Full
      length TGEV infectious viruses were generated with the optimized transcription
      regulating motif, which enhanced by 5-fold the transcription of the 3a gene and
      can be used in expression vectors based in coronavirus genomes.

PMID- 21715480
TI  - Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase
      enhancer of Zeste 2.
AB  - Latent HIV proviruses are silenced as the result of deacetylation and methylation
      of histones located at the viral long terminal repeat (LTR). Inhibition of
      histone deacetylases (HDACs) leads to the reemergence of HIV-1 from latency, but
      the contribution of histone lysine methyltransferases (HKMTs) to maintaining HIV
      latency remains uncertain. Chromatin immunoprecipitation experiments using
      latently infected Jurkat T-cell lines demonstrated that the HKMT enhancer of
      Zeste 2 (EZH2) was present at high levels at the LTR of silenced HIV proviruses
      and was rapidly displaced following proviral reactivation. Knockdown of EZH2, a
      key component of the Polycomb repressive complex 2 (PRC2) silencing machinery,
      and the enzyme which is required for trimethyl histone lysine 27 (H3K27me3)
      synthesis induced up to 40% of the latent HIV proviruses. In contrast, there was
      less than 5% induction of latent proviruses following knockdown of SUV39H1, which
      is required for H3K9me3 synthesis. Knockdown of EZH2 also sensitized latent
      proviruses to external stimuli, such as T-cell receptor stimulation, and slowed
      the reversion of reactivated proviruses to latency. Similarly, cell populations
      that responded poorly to external stimuli carried HIV proviruses that were
      enriched in H3K27me3 and relatively depleted in H3K9me3. Treating latently
      infected cells with the HKMT inhibitor 3-deazaneplanocin A, which targets EZH2,
      led to the reactivation of silenced proviruses, whereas chaetocin and BIX01294
      showed only minimal reactivation activities. These findings suggest that PRC2
      mediated silencing is an important feature of HIV latency and that inhibitors of
      histone methylation may play a useful role in induction strategies designed to
      eradicate latent HIV pools.

PMID- 21715481
TI  - Host factors in enterovirus 71 replication.
AB  - Enterovirus 71 (EV71) infections continue to remain an important public health
      problem around the world, especially in the Asia-Pacific region. There is a
      significant mortality rate following such infections, and there is neither any
      proven therapy nor a vaccine for EV71. This has spurred much fundamental research
      into the replication of the virus. In this review, we discuss recent work
      identifying host cell factors which regulate the synthesis of EV71 RNA and
      proteins. Three of these proteins, heterogeneous nuclear ribonucleoprotein A1
      (hnRNP A1), far-upstream element-binding protein 2 (FBP2), and FBP1 are nuclear
      proteins which in EV71-infected cells are relocalized to the cytoplasm, and they
      influence EV71 internal ribosome entry site (IRES) activity. hnRNP A1 stimulates
      IRES activity but can be replaced by hnRNP A2. FBP2 is a negative regulatory
      factor with respect to EV71 IRES activity, whereas FBP1 has the opposite effect.
      Two other proteins, hnRNP K and reticulon 3, are required for the efficient
      synthesis of viral RNA. The cleavage stimulation factor 64K subunit (CstF-64) is
      a host protein that is involved in the 3' polyadenylation of cellular pre-mRNAs,
      and recent work suggests that in EV71-infected cells, it may be cleaved by the
      EV71 3C protease. Such a cleavage would impair the processing of pre-mRNA to
      mature mRNAs. Host cell proteins play an important role in the replication of
      EV71, but much work remains to be done in order to understand how they act.

PMID- 21715482
TI  - M94 is essential for the secondary envelopment of murine cytomegalovirus.
AB  - The gene M94 of murine cytomegalovirus (MCMV) as well as its homologues UL16 in
      alphaherpesviruses is involved in viral morphogenesis. For a better understanding
      of its role in the viral life cycle, a library of random M94 mutants was
      generated by modified transposon-based linker scanning mutagenesis. A
      comprehensive set of M94 mutants was reinserted into the MCMV genome and tested
      for their capacity to complement the M94 null mutant. Thereby, 34 loss-of
      function mutants of M94 were identified, which were tested in a second screen for
      their capacity to inhibit virus replication. This analysis identified two N
      terminal insertion mutants of M94 with a dominant negative effect. We compared
      phenotypes induced by the conditional expression of these dominant negative M94
      alleles with the null phenotype of the M94 deletion. The viral gene expression
      cascade and the nuclear morphogenesis steps were not affected in either setting.
      In both cases, however, secondary envelopment did not proceed in the absence of
      functional M94, and capsids subsequently accumulated in the center of the
      cytoplasmic assembly complex. In addition, deletion of M94 resulted in a block of
      cell-to-cell spread. Moreover, the dominant negative mutant of M94 demonstrated a
      defect in interacting with M99, the UL11 homologue of MCMV.

PMID- 21715483
TI  - Replacement of previously circulating respiratory syncytial virus subtype B
      strains with the BA genotype in South Africa.
AB  - Respiratory syncytial virus (RSV) is a major cause of bronchiolitis and pneumonia
      in infants, the immunocompromised, and the elderly in both developed and
      developing countries. Reinfections are common, and G protein variability is one
      mechanism to overcome herd immunity. This is illustrated by the appearance of the
      BA genotype with a 60-nucleotide duplication dominating the subtype B genotypes
      in epidemics worldwide. To investigate the evolution of subtype B in South Africa
      since 2002, the genetic variability of the G protein was analyzed in all recent
      strains isolated over 4 years (2006 to 2009) in South African hospitals. Bayesian
      analysis revealed a replacement of all subtype B genotypes previously identified
      in South Africa with the BA genotype since 2006, while subtype A genotypes
      identified in previous years are still circulating. Compared to BA strains from
      other countries, the evolutionary rate of the South African BA genotype was shown
      to be 2.305 * 10(-3) nucleotide substitutions/site/year and drift was evident.
      The most recent common ancestor (MRCA) of the South African BA viruses was
      determined to date back to 1996. All South African BA isolates clustered with the
      BA-IV subgenotype, and the appearance of new subgenotypes within this branch may
      occur if drift continues. Sequencing of the complete G protein of selected South
      African strains revealed an additional 6-nucleotide deletion. Acquisition of the
      60-nucleotide duplication appeared to have improved the fitness of this virus,
      and more recent subtype B strains may need to be included in experimental
      vaccines to evaluate their efficacy in the current setting of evolved circulating
      strains.

PMID- 21715484
TI  - Replication-competent simian immunodeficiency virus (SIV) Gag escape mutations
      archived in latent reservoirs during antiretroviral treatment of SIV-infected
      macaques.
AB  - In response to pressure exerted by major histocompatibility complex (MHC) class I
      mediated CD8(+) T cell control, human immunodeficiency virus (HIV) escape
      mutations often arise in immunodominant epitopes recognized by MHC class I
      alleles. While the current standard of care for HIV-infected patients is
      treatment with highly active antiretroviral therapy (HAART), suppression of viral
      replication in these patients is not absolute and latently infected cells persist
      as lifelong reservoirs. To determine whether HIV escape from MHC class I
      restricted CD8(+) T cell control develops during HAART treatment and then enters
      latent reservoirs in the periphery and central nervous system (CNS), with the
      potential to emerge as replication-competent virus, we tracked the longitudinal
      development of the simian immunodeficiency virus (SIV) Gag escape mutation K165R
      in HAART-treated SIV-infected pigtailed macaques. Key findings of these studies
      included: (i) SIV Gag K165R escape mutations emerged in both plasma and
      cerebrospinal fluid (CSF) during the decaying phase of viremia after HAART
      initiation before suppression of viral replication, (ii) SIV K165R Gag escape
      mutations were archived in latent proviral DNA reservoirs, including the brain in
      animals receiving HAART that suppressed viral replication, and (iii) replication
      competent SIV Gag K165R escape mutations were present in the resting CD4(+) T
      cell reservoir in HAART-treated SIV-infected macaques. Despite early
      administration of aggressive antiretroviral treatment, HIV immune escape from
      CD8(+) T cell control can still develop during the decaying phases of viremia and
      then persist in latent reservoirs, including the brain, with the potential to
      emerge if HAART therapy is interrupted.

PMID- 21715485
TI  - Autocatalytic activity of the ubiquitin-specific protease domain of herpes
      simplex virus 1 VP1-2.
AB  - The herpes simplex virus (HSV) tegument protein VP1-2 is essential for virus
      entry and assembly. VP1-2 also contains a highly conserved ubiquitin-specific
      protease (USP) domain within its N-terminal region. Despite conservation of the
      USP and the demonstration that it can act on artificial substrates such as
      polyubiquitin chains, identification of the relevance of the USP in vivo to
      levels or function of any substrate remains limited. Here we show that HSV VP1-2
      USP can act on itself and is important for stability. VP1-2 N-terminal variants
      encompassing the core USP domain itself were not affected by mutation of the
      catalytic cysteine residue (C65). However, extending the N-terminal region
      resulted in protein species requiring USP activity for accumulation. In this
      context, C65A mutation resulted in a drastic reduction in protein levels which
      could be stabilized by proteosomal inhibition or by the presence of normal C65.
      The functional USP domain could increase abundance of unstable variants,
      indicating action at least in part, in trans. Interestingly, full-length variants
      containing the inactive USP, although unstable when expressed in isolation, were
      stabilized by virus infection. The catalytically inactive VP1-2 retained
      complementation activity of a VP1-2-negative virus. Furthermore, a recombinant
      virus expressing a C65A mutant VP1-2 exhibited little difference in single-step
      growth curves and the kinetics and abundance of VP1-2 or a number of test
      proteins. Despite the absence of a phenotype for these replication parameters,
      the USP activity of VP1-2 may be required for function, including its own
      stability, under certain circumstances.

PMID- 21715486
TI  - The human cytomegalovirus protein pUL38 suppresses endoplasmic reticulum stress
      mediated cell death independently of its ability to induce mTORC1 activation.
AB  - As obligate intracellular parasites, viruses not only hijack cellular machinery,
      they also deregulate host stress responses for their infection. Human
      cytomegalovirus (HCMV) modulates the endoplasmic reticulum (ER) stress response,
      due at least in part to the viral protein pUL38, and one of the consequences is
      to maintain the viability of infected cells. Consequently, pUL38-deficient virus
      induces premature cell death during infection. In addition, pUL38 activates
      mammalian target of rapamycin complex 1 (mTORC1), which may also antagonize other
      detrimental cellular stresses (N. J. Moorman et al., Cell Host Microbe 3:253-262,
      2008). It remains elusive how pUL38 inhibition of cell death is related to mTORC1
      activation. In this study, we defined the interplay of the two pUL38 activities.
      We constructed a series of pUL38 truncation mutants based on the secondary
      structure prediction and evolutionary conservation of its sequence. We found that
      the N-terminal 239 residues of pUL38 were necessary and sufficient to block cell
      death induced by pUL38-deficient virus or by the ER stress inducer tunicamycin.
      However, this pUL38 domain was unable to activate mTORC1 when expressed alone.
      Importantly, small-molecule inhibitors of mTORC1, rapamycin or torin 1, did not
      compromise pUL38 activity to block cell death in isolation or in virus infection.
      Expression of a constitutively active variant of an mTORC1 activator, Rheb (Ras
      homolog enriched in brain), could not prevent cell death induced by pUL38
      deficient virus. Collectively, we provide genetic and biochemical evidence that
      pUL38 prevents ER stress-induced cell death independent of its role in mTORC1
      activation.

PMID- 21715487
TI  - Mammalian orthoreovirus escape from host translational shutoff correlates with
      stress granule disruption and is independent of eIF2alpha phosphorylation and
      PKR.
AB  - In response to mammalian orthoreovirus (MRV) infection, cells initiate a stress
      response that includes eIF2alpha phosphorylation and protein synthesis
      inhibition. We have previously shown that early in infection, MRV activation of
      eIF2alpha phosphorylation results in the formation of cellular stress granules
      (SGs). In this work, we show that as infection proceeds, MRV disrupts SGs despite
      sustained levels of phosphorylated eIF2alpha and, further, interferes with the
      induction of SGs by other stress inducers. MRV interference with SG formation
      occurs downstream of eIF2alpha phosphorylation, suggesting the virus uncouples
      the cellular stress signaling machinery from SG formation. We additionally
      examined mRNA translation in the presence of SGs induced by eIF2alpha
      phosphorylation-dependent and -independent mechanisms. We found that irrespective
      of eIF2alpha phosphorylation status, the presence of SGs in cells correlated with
      inhibition of viral and cellular translation. In contrast, MRV disruption of SGs
      correlated with the release of viral mRNAs from translational inhibition, even in
      the presence of phosphorylated eIF2alpha. Viral mRNAs were also translated in the
      presence of phosphorylated eIF2alpha in PKR(-/-) cells. These results suggest
      that MRV escape from host cell translational shutoff correlates with virus
      induced SG disruption and occurs in the presence of phosphorylated eIF2alpha in a
      PKR-independent manner.

PMID- 21715488
TI  - Adenovirus E1A directly targets the E2F/DP-1 complex.
AB  - Deregulation of the cell cycle is of paramount importance during adenovirus
      infection. Adenovirus normally infects quiescent cells and must initiate the cell
      cycle in order to propagate itself. The pRb family of proteins controls entry
      into the cell cycle by interacting with and repressing transcriptional activation
      by the E2F transcription factors. The viral E1A proteins indirectly activate E2F
      dependent transcription and cell cycle entry, in part, by interacting with pRb
      and family members to free the E2Fs. We report here that an E1A 13S isoform can
      unexpectedly activate E2F-responsive gene expression independently of binding to
      the pRb family of proteins. We demonstrate that E1A binds to E2F/DP-1 complexes
      through a direct interaction with DP-1. E1A appears to utilize this binding to
      recruit itself to E2F-regulated promoters, and this allows the E1A 13S protein,
      but not the E1A 12S protein, to activate transcription independently of
      interaction with pRb. Importantly, expression of E1A 13S, but not E1A 12S, led to
      significant enhancement of E2F4 occupancy of E2F sites of two E2F-regulated
      promoters. These observations identify a novel mechanism by which adenovirus
      deregulates the cell cycle and suggest that E1A 13S may selectively activate a
      subset of E2F-regulated cellular genes during infection.

PMID- 21715489
TI  - NF-kappaB protects human papillomavirus type 38 E6/E7-immortalized human
      keratinocytes against tumor necrosis factor alpha and UV-mediated apoptosis.
AB  - Constitutive activation of NF-kappaB signaling is a key event in virus- and non
      virus-induced carcinogenesis. We have previously reported that cutaneous human
      papillomavirus type 38 (HPV38) displays transforming properties in in vitro and
      in vivo experimental models. However, the involvement of NF-kappaB signaling in
      HPV38-induced cell growth transformation remains to be determined. In this study,
      we showed that HPV38 E6 and E7 activate NF-kappaB and that inhibition of the
      pathway with the IkappaBalpha superrepressor sensitizes HPV38E6E7-immortalized
      human keratinocytes to tumor necrosis factor alpha (TNF-alpha)- and UVB radiation
      mediated apoptosis. Accordingly, inhibition of NF-kappaB signaling resulted in
      the downregulation of NF-kappaB-regulated antiapoptotic genes, including cIAP1,
      cIAP2, and xIAP genes. These findings demonstrate a critical role of NF-kappaB
      activity in the survival of HPV38E6E7-immortalized human keratinocytes exposed to
      cytokine or UV radiation. Our data provide additional evidence for cooperation
      between beta HPV infection and UV irradiation in skin carcinogenesis.

PMID- 21715490
TI  - Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody
      VRC01.
AB  - The structure of VRC01 in complex with the HIV-1 gp120 core reveals that this
      broadly neutralizing CD4 binding site (CD4bs) antibody partially mimics the
      interaction of the primary virus receptor, CD4, with gp120. Here, we extended the
      investigation of the VRC01-gp120 core interaction to the biologically relevant
      viral spike to better understand the mechanism of VRC01-mediated neutralization
      and to define viral elements associated with neutralization resistance. In
      contrast to the interaction of CD4 or the CD4bs monoclonal antibody (MAb) b12
      with the HIV-1 envelope glycoprotein (Env), occlusion of the VRC01 epitope by
      quaternary constraints was not a major factor limiting neutralization.
      Mutagenesis studies indicated that VRC01 contacts within the gp120 loop D, the
      CD4 binding loop, and the V5 region were necessary for optimal VRC01
      neutralization, as suggested by the crystal structure. In contrast to
      interactions with the soluble gp120 monomer, VRC01 interaction with the native
      viral spike did not occur in a CD4-like manner; VRC01 did not induce gp120
      shedding from the Env spike or enhance gp41 membrane proximal external region
      (MPER)-directed antibody binding to the Env spike. Finally, VRC01 did not display
      significant reactivity with human antigens, boding well for potential in vivo
      applications. The data indicate that VRC01 interacts with gp120 in the context of
      the functional spike in a manner distinct from that of CD4. It achieves potent
      neutralization by precisely targeting the CD4bs without requiring alterations of
      Env spike configuration and by avoiding steric constraints imposed by the
      quaternary structure of the functional Env spike.

PMID- 21715491
TI  - Human leukocyte antigen variants B*44 and B*57 are consistently favorable during
      two distinct phases of primary HIV-1 infection in sub-Saharan Africans with
      several viral subtypes.
AB  - As part of an ongoing study of early human immunodeficiency virus type 1 (HIV-1)
      infection in sub-Saharan African countries, we have identified 134 seroconverters
      (SCs) with distinct acute-phase (peak) and early chronic-phase (set-point)
      viremias. SCs with class I human leukocyte antigen (HLA) variants B*44 and B*57
      had much lower peak viral loads (VLs) than SCs without these variants (adjusted
      linear regression beta values of -1.08 +/- 0.26 log(10) [mean +/- standard error]
      and -0.83 +/- 0.27 log(10), respectively; P < 0.005 for both), after accounting
      for several nongenetic factors, including gender, age at estimated date of
      infection, duration of infection, and country of origin. These findings were
      confirmed by alternative models in which major viral subtypes (A1, C, and others)
      in the same SCs replaced country of origin as a covariate (P <= 0.03). Both B*44
      and B*57 were also highly favorable (P <= 0.03) in analyses of set-point VLs.
      Moreover, B*44 was associated with relatively high CD4(+) T-cell counts during
      early chronic infection (P = 0.02). Thus, at least two common HLA-B variants
      showed strong influences on acute-phase as well as early chronic-phase VL,
      regardless of the infecting viral subtype. If confirmed, the identification of
      B*44 as another favorable marker in primary HIV-1 infection should help dissect
      mechanisms of early immune protection against HIV-1 infection.

PMID- 21715492
TI  - Activation of the retroviral budding factor ALIX.
AB  - The cellular ALIX protein functions within the ESCRT pathway to facilitate
      intralumenal endosomal vesicle formation, the abscission stage of cytokinesis,
      and enveloped virus budding. Here, we report that the C-terminal proline-rich
      region (PRR) of ALIX folds back against the upstream domains and auto-inhibits V
      domain binding to viral late domains. Mutations designed to destabilize the
      closed conformation of the V domain opened the V domain, increased ALIX membrane
      association, and enhanced virus budding. These observations support a model in
      which ALIX activation requires dissociation of the autoinhibitory PRR and opening
      of the V domain arms.

PMID- 21715493
TI  - Passive immunotherapies protect WRvFire and IHD-J-Luc vaccinia virus-infected
      mice from lethality by reducing viral loads in the upper respiratory tract and
      internal organs.
AB  - Whole-body bioimaging was employed to study the effects of passive
      immunotherapies on lethality and viral dissemination in BALB/c mice challenged
      with recombinant vaccinia viruses expressing luciferase. WRvFire and IHD-J-Luc
      vaccinia viruses induced lethality with similar times to death following
      intranasal infection, but WRvFire replicated at higher levels than IHD-J-Luc in
      the upper and lower respiratory tracts. Three types of therapies were tested:
      licensed human anti-vaccinia virus immunoglobulin intravenous (VIGIV);
      recombinant anti-vaccinia virus immunoglobulin (rVIG; Symphogen, Denmark), an
      investigational product containing a mixture of 26 human monoclonal antibodies
      (HuMAbs) against mature virion (MV) and enveloped virion (EV); and HuMAb
      compositions targeting subsets of MV or EV proteins. Bioluminescence recorded
      daily showed that pretreatment with VIGIV (30 mg) or with rVIG (100 MUg) on day 
      2 protected mice from death but did not prevent viral replication at the site of
      inoculation and dissemination to internal organs. Compositions containing HuMAbs
      against MV or EV proteins were protective in both infection models at 100 MUg per
      animal, but at 30 MUg, only anti-EV antibodies conferred protection. Importantly,
      the t statistic of the mean total fluxes revealed that viral loads in surviving
      mice were significantly reduced in at least 3 sites for 3 consecutive days (days
      3 to 5) postchallenge, while significant reduction for 1 or 2 days in any
      individual site did not confer protection. Our data suggest that reduction of
      viral replication at multiple sites, including respiratory tract, spleen, and
      liver, as monitored by whole-body bioluminescence can be used to predict the
      effectiveness of passive immunotherapies in mouse models.

PMID- 21715494
TI  - Novel histone H3 binding protein ORF158L from the Singapore grouper iridovirus.
AB  - Singapore grouper iridovirus (SGIV), a major pathogen of concern for grouper
      aquaculture, has a double-stranded DNA (dsDNA) genome with 162 predicted open
      reading frames, for which a total of 62 SGIV proteins have been identified. One
      of these, ORF158L, bears no sequence homology to any other known protein.
      Knockdown of orf158L using antisense morpholino oligonucleotides resulted in a
      significant decrease in virus yield in grouper embryonic cells. ORF158L was
      observed in nuclei and virus assembly centers of virus-infected cells. This
      observation led us to study the structure and function of ORF158L. The crystal
      structure determined at 2.2-A resolution reveals that ORF158L partially exhibits
      a structural resemblance to the histone binding region of antisilencing factor 1
      (Asf1), a histone H3/H4 chaperon, despite the fact that there is no significant
      sequence identity between the two proteins. Interactions of ORF158L with the
      histone H3/H4 complex and H3 were demonstrated by isothermal titration
      calorimetry (ITC) experiments. Subsequently, the results of ITC studies on
      structure-based mutants of ORF158L suggested Arg67 and Ala93 were key residues
      for histone H3 interactions. Moreover, a combination of approaches of ORF158L
      knockdown and isobaric tags/mass spectrometry for relative and absolute
      quantifications (iTRAQ) revealed that ORF158L may be involved in both the
      regulation and the expression of histone H3 and H3 methylation. Our present
      studies suggest that ORF158L may function as a histone H3 chaperon, enabling it
      to control host cellular gene expression and to facilitate viral replication.

PMID- 21715495
TI  - Prion disease detection, PMCA kinetics, and IgG in urine from sheep
      naturally/experimentally infected with scrapie and deer with preclinical/clinical
      chronic wasting disease.
AB  - Prion diseases, also known as transmissible spongiform encephalopathies, are
      fatal neurodegenerative disorders. Low levels of infectious agent and limited,
      infrequent success of disease transmissibility and PrP(Sc) detection have been
      reported with urine from experimentally infected clinical cervids and rodents. We
      report the detection of prion disease-associated seeding activity (PASA) in urine
      from naturally and orally infected sheep with clinical scrapie agent and orally
      infected preclinical and infected white-tailed deer with clinical chronic wasting
      disease (CWD). This is the first report on PASA detection of PrP(Sc) from the
      urine of naturally or preclinical prion-diseased ovine or cervids. Detection was
      achieved by using the surround optical fiber immunoassay (SOFIA) to measure the
      products of limited serial protein misfolding cyclic amplification (sPMCA).
      Conversion of PrP(C) to PrP(Sc) was not influenced by the presence of poly(A)
      during sPMCA or by the homogeneity of the PrP genotypes between the PrP(C) source
      and urine donor animals. Analysis of the sPMCA-SOFIA data resembled a linear,
      rather than an exponential, course. Compared to uninfected animals, there was a 2
      to 4-log increase of proteinase K-sensitive, light chain immunoglobulin G (IgG)
      fragments in scrapie-infected sheep but not in infected CWD-infected deer. The
      higher-than-normal range of IgG levels found in the naturally and experimentally
      infected clinical scrapie-infected sheep were independent of their genotypes.
      Although analysis of urine samples throughout the course of infection would be
      necessary to determine the usefulness of altered IgG levels as a disease
      biomarker, detection of PrP(Sc) from PASA in urine points to its potential value
      for antemortem diagnosis of prion diseases.

PMID- 21715496
TI  - Engineered single human CD4 domains as potent HIV-1 inhibitors and components of
      vaccine immunogens.
AB  - Soluble forms of the HIV-1 receptor CD4 (sCD4) have been extensively
      characterized for more than 2 decades as promising inhibitors and components of
      vaccine immunogens. However, they were mostly based on the first two CD4 domains
      (D1D2), and numerous attempts to develop functional, high-affinity, stable
      soluble one-domain sCD4 (D1) have not been successful because of the strong
      interactions between the two domains. We have hypothesized that combining the
      power of structure-based design with sequential panning of large D1 mutant
      libraries against different HIV-1 envelope glycoproteins (Envs) and screening for
      soluble mutants could not only help solve the fundamental stability problem of
      isolated D1, but may also allow improvement of D1 affinity while preserving its
      cross-reactivity. By using this strategy, we identified two stable monomeric D1
      mutants, mD1.1 and mD1.2, which were significantly more soluble and bound Env
      gp120s more strongly (50-fold) than D1D2, neutralized a panel of HIV-1 primary
      isolates from different clades more potently than D1D2, induced conformational
      changes in gp120, and sensitized HIV-1 for neutralization by CD4-induced
      antibodies. mD1.1 and mD1.2 exhibited much lower binding to human blood cell
      lines than D1D2; moreover, they preserved a beta-strand secondary structure and
      stability against thermally induced unfolding, trypsin digestion, and degradation
      by human serum. Because of their superior properties, mD1.1 and mD1.2 could be
      potentially useful as candidate therapeutics, components of vaccine immunogens,
      and research reagents for exploration of HIV-1 entry and immune responses. Our
      approach could be applied to other cases where soluble isolated protein domains
      are needed.

PMID- 21715497
TI  - Potent and broad anti-HIV-1 activity exhibited by a glycosyl-phosphatidylinositol
      anchored peptide derived from the CDR H3 of broadly neutralizing antibody PG16.
AB  - PG9 and PG16 are two recently isolated quaternary-specific human monoclonal
      antibodies that neutralize 70 to 80% of circulating HIV-1 isolates. The crystal
      structure of PG16 shows that it contains an exceptionally long CDR H3 that forms
      a unique stable subdomain that towers above the antibody surface to confer fine
      specificity. To determine whether this unique architecture of CDR H3 itself is
      sufficient for epitope recognition and neutralization, we cloned CDR H3
      subdomains derived from human monoclonal antibodies PG16, PG9, b12, E51, and AVF
      and genetically linked them to a glycosyl-phosphatidylinositol (GPI) attachment
      signal. Each fusion gene construct is expressed and targeted to lipid rafts of
      plasma membranes through a GPI anchor. Moreover, GPI-CDR H3(PG16, PG9, and E51),
      but not GPI-CDR H3(b12 and AVF), specifically neutralized multiple clades of HIV
      1 isolates with a great degree of potency when expressed on the surface of
      transduced TZM-bl cells. Furthermore, GPI-anchored CDR H3(PG16), but not GPI
      anchored CDR H3(AVF), specifically confers resistance to HIV-1 infection when
      expressed on the surface of transduced human CD4(+) T cells. Finally, the CDR H3
      mutations (Y100HF, D100IA, and G7) that were previously shown to compromise the
      neutralization activity of antibody PG16 also abolished the neutralization
      activity of GPI-CDR H3(PG16). Thus, we conclude that the CDR H3 subdomain of PG16
      neutralizes HIV-1 when targeted to the lipid raft of the plasma membrane of HIV-1
      susceptible cells and that GPI-CDR H3 can be an alternative approach for
      determining whether the CDR H3 of certain antibodies alone can exert epitope
      recognition and neutralization.

PMID- 21715498
TI  - Analysis of intrahost variation in Venezuelan equine encephalitis virus reveals
      repeated deletions in the 6-kilodalton protein gene.
AB  - RNA viruses exist as a spectrum of mutants that is generated and maintained
      during replication within the host. Consensus sequencing overlooks minority
      genotypes present in the viral sample that may impact the population's phenotype.
      In-depth sequencing of an original field isolate of subtype IE Venezuelan equine
      encephalitis virus (VEEV) demonstrated the presence of multiple deletions within
      the 6,000-molecular-weight (6K) protein gene. Using in vitro and in vivo
      experiments, similar deletions were generated in an additional VEEV strain
      originating from an infectious cDNA clone. Time course experiments demonstrated
      that the deletions are produced during acute infection although not until 24 h
      postinfection. Molecular clones containing some of these deletions were
      generated, and although the larger deletions appear to be noninfectious, viruses
      with the smaller deletions were viable and formed small plaques. Serial passages
      provided no evidence that these deletion mutants function as defective
      interfering particles. Furthermore, since wild-type infections generally occur at
      a low multiplicity of infection, it is unlikely that these deletions are
      propagated in natural transmission cycles. However, they could affect
      pathogenesis at later stages of infection. Because they are ubiquitously
      generated both in vivo and in vitro, further investigation is warranted to
      understand the generation of these deletions and their significance for disease.

PMID- 21715499
TI  - Targeting OX40 promotes lung-resident memory CD8 T cell populations that protect
      against respiratory poxvirus infection.
AB  - One goal of vaccination is to promote development of mucosal effector cells that
      can immediately respond to peripheral infection. This is especially important for
      protection against viruses that enter the host through the respiratory tract. We
      show that targeting the OX40 costimulatory receptor (CD134) strongly promotes
      mucosal memory in the CD8 T cell compartment. Systemic injection of an agonist
      antibody to OX40 strongly enhanced development of polyfunctional effector CD8 T
      cells that were induced after intraperitoneal infection with a highly virulent
      strain of vaccinia virus. These cells were located in lymphoid organs and also
      the lung, and importantly, long-term memory CD8 T cells were maintained in the
      lung over 1 year. Anti-OX40 also boosted memory development when mice were
      vaccinated subcutaneously with viral peptide. These CD8 T cells were sufficient
      to provide protection from lethal respiratory infection with live vaccinia virus
      independent of CD4 T cells and antibody. Again, the CD8 T cell populations that
      were induced after secondary infection displayed polyfunctionality and were
      maintained in the lung for over a year. These data suggest that agonists to the
      OX40 costimulatory receptor represent potential candidates for incorporation into
      vaccines for respiratory viruses.

PMID- 21715500
TI  - Gouleako virus isolated from West African mosquitoes constitutes a proposed novel
      genus in the family Bunyaviridae.
AB  - The family Bunyaviridae is the most diversified family of RNA viruses. We
      describe a novel prototypic bunyavirus, tentatively named Gouleako virus,
      isolated from various mosquito species trapped in Cote d'Ivoire. The S segment
      comprised 1,087 nucleotides (nt), the M segment 3,188 nt, and the L segment 6,358
      nt, constituting the shortest bunyavirus genome known so far. The virus had
      shorter genome termini than phleboviruses and showed no evidence of encoded NSs
      and NSm proteins. An uncharacterized 105-amino-acid (aa) putative open reading
      frame (ORF) was detected in the S segment. Genetic equidistance to other
      bunyaviruses (74 to 88% aa identity) and absence of serological cross-reactivity
      with phleboviruses suggested a proposed novel Bunyaviridae genus.

PMID- 21715501
TI  - CD4-like immunological function by CD4- T cells in multiple natural hosts of
      simian immunodeficiency virus.
AB  - Many species of African nonhuman primates are natural hosts for individual
      strains of simian immunodeficiency virus (SIV). These infected animals do not,
      however, develop AIDS. Here we show that multiple species of African nonhuman
      primate species characteristically have low frequencies of CD4(+) T cells and
      high frequencies of both T cells that express only the alpha-chain of CD8 and
      double-negative T cells. These subsets of T cells are capable of eliciting
      functions generally associated with CD4(+) T cells, yet these cells lack surface
      expression of the CD4 protein and are, therefore, poor targets for SIV in vivo.
      These data demonstrate that coevolution with SIV has, in several cases, involved
      downregulation of receptors for the virus by otherwise-susceptible host target
      cells. Understanding the genetic factors that lead to downregulation of these
      receptors may lead to therapeutic interventions that mimic this modulation in
      progressive infections.

PMID- 21715502
TI  - Mouse hepatitis virus stem-loop 4 functions as a spacer element required to drive
      subgenomic RNA synthesis.
AB  - The 5' 140 nucleotides of the mouse hepatitis virus (MHV) 5' untranslated region
      (5'UTR) are predicted to contain three secondary structures, stem-loop 1 (SL1),
      SL2, and SL4. SL1 and SL2 are required for subgenomic RNA synthesis. The current
      study focuses on SL4, which contains two base-paired regions, SL4a and SL4b. A
      series of reverse genetic experiments show that SL4a is not required to be base
      paired. Neither the structure, the sequence, nor the putative 8-amino-acid open
      reading frame (ORF) in SL4b is required for viral replication. Viruses containing
      separate deletions of SL4a and SL4b are viable. However, deletion of SL4 is
      lethal, and genomes carrying this deletion are defective in directing subgenomic
      RNA synthesis. Deletion of (131)ACA(133) just 3' to SL4 has a profound impact on
      viral replication. Viruses carrying the (131)ACA(133) deletion were heterogeneous
      in plaque size. We isolated three viruses with second-site mutations in the 5'UTR
      which compensated for decreased plaque sizes, delayed growth kinetics, and lower
      titers associated with the (131)ACA(133) deletion. The second-site mutations are
      predicted to change either the spacing between SL1 and SL2 or that between SL2
      and SL4 or to destabilize the proximal portion of SL4a in our model. A mutant
      constructed by replacing SL4 with a shorter sequence-unrelated stem-loop was
      viable. These results suggest that the proposed SL4 in the MHV 5'UTR functions in
      part as a spacer element that orients SL1, SL2, and the transcriptional
      regulatory sequence (TRS), and this spacer function may play an important role in
      directing subgenomic RNA synthesis.

PMID- 21715503
TI  - Structural analysis of histo-blood group antigen binding specificity in a
      norovirus GII.4 epidemic variant: implications for epochal evolution.
AB  - Susceptibility to norovirus (NoV), a major pathogen of epidemic gastroenteritis,
      is associated with histo-blood group antigens (HBGAs), which are also cell
      attachment factors for this virus. GII.4 NoV strains are predominantly associated
      with worldwide NoV epidemics with a periodic emergence of new variants. The
      sequence variations in the surface-exposed P domain of the capsid protein
      resulting in differential HBGA binding patterns and antigenicity are suggested to
      drive GII.4 epochal evolution. To understand how temporal sequence variations
      affect the P domain structure and contribute to epochal evolution, we determined
      the P domain structure of a 2004 variant with ABH and secretor Lewis HBGAs and
      compared it with the previously determined structure of a 1996 variant. We show
      that temporal sequence variations do not affect the binding of monofucosyl ABH
      HBGAs but that they can modulate the binding strength of difucosyl Lewis HBGAs
      and thus could contribute to epochal evolution by the potentiated targeting of
      new variants to Lewis-positive, secretor-positive individuals. The temporal
      variations also result in significant differences in the electrostatic
      landscapes, likely reflecting antigenic variations. The proximity of some of
      these changes to the HBGA binding sites suggests the possibility of a coordinated
      interplay between antigenicity and HBGA binding in epochal evolution. From the
      observation that the regions involved in the formation of the HBGA binding sites
      can be conformationally flexible, we suggest a plausible mechanism for how
      norovirus disassociates from salivary mucin-linked HBGA before reassociating with
      HBGAs linked to intestinal epithelial cells during its passage through the
      gastrointestinal tract.

PMID- 21715504
TI  - Comparative evolution of GII.3 and GII.4 norovirus over a 31-year period.
AB  - Noroviruses are the most common cause of epidemic gastroenteritis. Genotype II.3
      is one of the most frequently detected noroviruses associated with sporadic
      infections. We studied the evolution of the major capsid gene from seven archival
      GII.3 noroviruses collected during a cross-sectional study at the Children's
      Hospital in Washington, DC, from 1975 through 1991, together with capsid sequence
      from 56 strains available in GenBank. Evolutionary analysis concluded that GII.3
      viruses evolved at a rate of 4.16 * 10(-3) nucleotide substitutions/site/year
      (strict clock), which is similar to that described for the more prevalent GII.4
      noroviruses. The analysis of the amino acid changes over the 31-year period found
      that GII.3 viruses evolve at a relatively steady state, maintaining 4% distance,
      and have a tendency to revert back to previously used residues while preserving
      the same carbohydrate binding profile. In contrast, GII.4 viruses demonstrate
      increasing rates of distance over time because of the continued integration of
      new amino acids and changing HBGA binding patterns. In GII.3 strains, seven sites
      acting under positive selection were predicted to be surface-exposed residues in
      the P2 domain, in contrast to GII.4 positively selected sites located primarily
      in the shell domain. Our study suggests that GII.3 noroviruses caused disease as
      early as 1975 and that they evolve via a specific pattern, responding to
      selective pressures induced by the host rather than presenting a nucleotide
      evolution rate lower than that of GII.4 noroviruses, as previously proposed.
      Understanding the evolutionary dynamics of prevalent noroviruses is relevant to
      the development of effective prevention and control strategies.

PMID- 21715505
TI  - The role of amino-terminal sequences in cellular localization and antiviral
      activity of APOBEC3B.
AB  - Human APOBEC3B (A3B) has been described as a potent inhibitor of retroviral
      infection and retrotransposition. However, we found that the predominantly
      nuclear A3B only weakly restricted infection by HIV-1, HIV-1Deltavif, and human T
      cell leukemia virus type 1 (HTLV-1), while significantly inhibiting LINE-1
      retrotransposition. The chimeric construct A3G/B, in which the first 60 amino
      acids of A3B were replaced with those of A3G, restricted HIV-1, HIV-1Deltavif,
      and HTLV-1 infection, as well as LINE-1 retrotransposition. In contrast to the
      exclusively cytoplasmic A3G, which is inactive against LINE-1 retrotransposition,
      the A3G/B protein, while localized mainly to the cytoplasm, was also present in
      the nucleus. Further mutational analysis revealed that residues 18, 19, 22, and
      24 in A3B were the major determinants for nuclear versus cytoplasmic localization
      and antiretroviral activity. HIV-1Deltavif packages A3G, A3B, and A3G/B into
      particles with close-to-equal efficiencies. Mutation E68Q or E255Q in the active
      centers of A3G/B resulted in loss of the inhibitory activity against HIV
      1Deltavif, while not affecting activity against LINE-1 retrotransposition. The
      low inhibition of HIV-1Deltavif by A3B correlated with a low rate of G-to-A
      hypermutation. In contrast, viruses that had been exposed to A3G/B showed a high
      number of G-to-A transitions. The mutation pattern was similar to that previously
      reported for A3B, with a preference for the GA context. In summary, these
      observations suggest that changing 4 residues in the amino terminus of A3B not
      only retargets the protein from the nucleus to the cytoplasm but also enhances
      its ability to restrict HIV while retaining inhibition of retrotransposition.

PMID- 21715506
TI  - Comprehensive proteomic analysis of influenza virus polymerase complex reveals a
      novel association with mitochondrial proteins and RNA polymerase accessory
      factors.
AB  - The trimeric RNA polymerase complex (3P, for PA-PB1-PB2) of influenza A virus
      (IAV) is an important viral determinant of pathogenicity and host range
      restriction. Specific interactions of the polymerase complex with host proteins
      may be determining factors in both of these characteristics and play important
      roles in the viral life cycle. To investigate this question, we performed a
      comprehensive proteomic analysis of human host proteins associated with the
      polymerase of the well-characterized H5N1 Vietnam/1203/04 isolate. We identified
      over 400 proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS),
      of which over 300 were found to bind to the PA subunit alone. The most intriguing
      and novel finding was the large number of mitochondrial proteins (~20%) that
      associated with the PA subunit. These proteins mediate molecular transport across
      the mitochondrial membrane or regulate membrane potential and may in concert with
      the identified mitochondrion-associated apoptosis inducing factor (AIFM1) have
      roles in the induction of apoptosis upon association with PA. Additionally, we
      identified host factors that associated with the PA-PB1 (68 proteins) and/or the
      3P complex (34 proteins) including proteins that have roles in innate antiviral
      signaling (e.g., ZAPS or HaxI) or are cellular RNA polymerase accessory factors
      (e.g., polymerase I transcript release factor [PTRF] or Supt5H). IAV strain
      specific host factor binding to the polymerase was not observed in our analysis.
      Overall, this study has shed light into the complex contributions of the IAV
      polymerase to host cell pathogenicity and allows for direct investigations into
      the biological significance of these newly described interactions.

PMID- 21715507
TI  - Phenotypic and immunologic comparison of clade B transmitted/founder and chronic
      HIV-1 envelope glycoproteins.
AB  - Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across mucosal
      barriers is responsible for the vast majority of new infections. This relatively
      inefficient process results in the transmission of a single transmitted/founder
      (T/F) virus, from a diverse viral swarm in the donor, in approximately 80% of
      cases. Here we compared the biological activities of 24 clade B T/F envelopes
      (Envs) with those from 17 chronic controls to determine whether the genetic
      bottleneck that occurs during transmission is linked to a particular Env
      phenotype. To maximize the likelihood of an intact mucosal barrier in the
      recipients and to enhance the sensitivity of detecting phenotypic differences,
      only T/F Envs from individuals infected with a single T/F variant were selected.
      Using pseudotyping to assess Env function in single-round infectivity assays, we
      compared coreceptor tropism, CCR5 utilization efficiencies, primary CD4(+) T cell
      subset tropism, dendritic cell trans-infections, fusion kinetics, and
      neutralization sensitivities. T/F and chronic Envs were phenotypically equivalent
      in most assays; however, T/F Envs were modestly more sensitive to CD4 binding
      site antibodies b12 and VRC01, as well as pooled human HIV Ig. This finding was
      independently validated with a panel of 14 additional chronic HIV-1 Env controls.
      Moreover, the enhanced neutralization sensitivity was associated with more
      efficient binding of b12 and VRC01 to T/F Env trimers. These data suggest that
      there are subtle but significant structural differences between T/F and chronic
      clade B Envs that may have implications for HIV-1 transmission and the design of
      effective vaccines.

PMID- 21715508
TI  - Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta
      analysis of 14 randomized controlled trials.
AB  - BACKGROUND: The effect of green tea beverage and green tea extract on lipid
      changes is controversial. OBJECTIVE: We aimed to identify and quantify the effect
      of green tea and its extract on total cholesterol (TC), LDL cholesterol, and HDL
      cholesterol. DESIGN: We performed a comprehensive literature search to identify
      relevant trials of green tea beverages and extracts on lipid profiles in adults.
      Weighted mean differences were calculated for net changes in lipid concentrations
      by using fixed-effects or random-effects models. Study quality was assessed by
      using the Jadad score, and a meta-analysis was conducted. RESULTS: Fourteen
      eligible randomized controlled trials with 1136 subjects were enrolled in our
      current meta-analysis. Green tea consumption significantly lowered the TC
      concentration by 7.20 mg/dL (95% CI: -8.19, -6.21 mg/dL; P < 0.001) and
      significantly lowered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: 
      3.16, -1.21 mg/dL; P < 0.001). The mean change in blood HDL-cholesterol
      concentration was not significant. Subgroup and sensitivity analyses showed that
      these changes were not influenced by the type of intervention, treatment dose of
      green tea catechins, study duration, individual health status, or quality of the
      study. Overall, no significant heterogeneity was detected for TC, LDL
      cholesterol, and HDL cholesterol; and results were reported on the basis of fixed
      effects models. CONCLUSION: The analysis of eligible studies showed that the
      administration of green tea beverages or extracts resulted in significant
      reductions in serum TC and LDL-cholesterol concentrations, but no effect on HDL
      cholesterol was observed.

PMID- 21715509
TI  - Yellow maize with high beta-carotene is an effective source of vitamin A in
      healthy Zimbabwean men.
AB  - BACKGROUND: The bioconversion efficiency of yellow maize beta-carotene to retinol
      in humans is unknown. OBJECTIVE: The objective of this study was to determine the
      vitamin A value of yellow maize beta-carotene in humans. DESIGN: High beta
      carotene-containing yellow maize was grown in a hydroponic medium with 23 atom%
      (2)H(2)O during grain development. Yellow maize beta-carotene showed the highest
      abundance of enrichment as [(2)H(9)]beta-carotene. Eight healthy Zimbabwean men
      volunteered for the study. On day 1 after a fasting blood draw, subjects consumed
      300 g yellow maize porridge containing 1.2 mg beta-carotene, 20 g butter, and a
      0.5-g corn oil capsule. On day 8, fasting blood was drawn, and subjects consumed
      1 mg [(13)C(10)]retinyl acetate in a 0.5-g corn oil capsule and 300 g white maize
      porridge with 20 g butter. Thirty-six blood samples were collected from each
      subject over 36 d. Concentrations and enrichments of retinol and beta-carotene in
      labeled doses and serum were determined with the use of HPLC, gas chromatography
      mass spectrometry, and liquid chromatography-mass spectrometry. RESULTS: The area
      under the curve (AUC) of retinol from 1.2 mg yellow maize beta-carotene was 72.9
      nmol . d, and the AUC of retinol from 1 mg retinyl acetate (13)C(10) was 161.1
      nmol . d. The conversion factor of yellow maize beta-carotene to retinol by
      weight was 3.2 +/- 1.5 to 1. CONCLUSION: In 8 healthy Zimbabwean men, 300 g
      cooked yellow maize containing 1.2 mg beta-carotene that was consumed with 20.5 g
      fat showed the same vitamin A activity as 0.38 mg retinol and provided 40-50% of
      the adult vitamin A Recommended Dietary Allowance. This trial was registered at
      clinicaltrials.gov as NCT00636038.

PMID- 21715510
TI  - Short sleep duration increases energy intakes but does not change energy
      expenditure in normal-weight individuals.
AB  - BACKGROUND: Evidence suggests a relation between short sleep duration and
      obesity. OBJECTIVE: We assessed energy balance during periods of short and
      habitual sleep in normal-weight men and women. DESIGN: Fifteen men and 15 women
      aged 30-49 y with a body mass index (in kg/m(2)) of 22-26, who regularly slept 7
      9 h/night, were recruited to participate in this crossover inpatient study. All
      participants were studied under short (4 h/night) and habitual (9 h/night) sleep
      conditions, in random order, for 5 nights each. Food intake was measured on day
      5, and energy expenditure was measured with the doubly labeled water method over
      each period. RESULTS: Participants consumed more energy on day 5 during short
      sleep (2813.6 +/- 593.0 kcal) than during habitual sleep (2517.7 +/- 593.0 kcal;
      P = 0.023). This effect was mostly due to increased consumption of fat (20.7 +/-
      37.4 g; P = 0.01), notably saturated fat (8.7 +/- 20.4 g; P = 0.038), during
      short sleep. Resting metabolic rate (short sleep: 1455.4 +/- 129.0 kcal/d;
      habitual sleep: 1486.5 +/- 129.5 kcal/d; P = 0.136) and total energy expenditure
      (short sleep: 2589.2 +/- 526.5 kcal/d; habitual sleep: 2611.1 +/- 529.0 kcal/d; P
      = 0.832) did not differ significantly between sleep phases. CONCLUSIONS: Our data
      show that a reduction in sleep increases energy and fat intakes, which may
      explain the associations observed between sleep and obesity. If sustained, as
      observed, and not compensated by increased energy expenditure, the dietary
      intakes of individuals undergoing short sleep predispose to obesity. This trial
      is registered at clinicaltrials.gov as NCT00935402.

PMID- 21715511
TI  - Vitamin A: biomarkers of nutrition for development.
AB  - Vitamin A is essential for multiple functions in mammals. Without vitamin A,
      mammals cannot grow, reproduce, or fight off disease. Because of its numerous
      functions in humans, biomarkers of vitamin A status are quite diverse. Assessment
      of liver reserves of vitamin A is considered the gold standard because the liver
      is the major storage organ. However, this measure is not feasible in human
      studies. Alternative biomarkers of status can be classified as biological,
      functional, histologic, and biochemical. Historically, signs of xerophthalmia
      were used to determine vitamin A deficiency. Before overt clinical damage to the
      eye, individuals who suffer from vitamin A deficiency are plagued by night
      blindness and longer vision-restoration times. These types of assessments require
      large population-based evaluations. Therefore, surrogate biochemical measures of
      vitamin A status, as defined by liver reserves, have been developed. Serum
      retinol concentrations are a common method used to evaluate vitamin A deficiency.
      Serum retinol concentrations are homeostatically controlled until liver reserves
      are dangerously low. Therefore, other biochemical methods that respond to liver
      reserves in the marginal category were developed. These included dose-response
      tests and isotope dilution assays. Dose-response tests work on the principle that
      apo-retinol-binding protein builds up in the liver as liver reserves become
      depleted. A challenge dose of vitamin A binds to this protein, and serum
      concentrations increase within a few hours if liver vitamin A concentrations are
      low. Isotope dilution assays use stable isotopes as tracers of total body
      reserves of vitamin A and evaluate a wide range of liver reserves. Resources
      available and study objectives often dictate the choice of a biomarker.

PMID- 21715512
TI  - Iron-containing micronutrient powder provided to children with moderate-to-severe
      malnutrition increases hemoglobin concentrations but not the risk of infectious
      morbidity: a randomized, double-blind, placebo-controlled, noninferiority safety
      trial.
AB  - BACKGROUND: A link between the provision of iron and infectious morbidity has
      been suggested, particularly in children with malnutrition. Two meta-analyses
      concluded that iron is not harmful, but malnourished children were
      underrepresented in most available studies. OBJECTIVE: This study evaluated the
      effect of iron-containing micronutrient powder (iron MNP) on infectious
      morbidities when provided to children with moderate-to-severe malnutrition and
      anemia. DESIGN: A randomized, double-blind, placebo-controlled, noninferiority
      safety trial using a 2-mo course of daily iron MNP or placebo powder (PP) was
      conducted in 268 Bangladeshi children aged 12-24 mo with moderate-to-severe
      malnutrition (weight-for-age z score <= -2) and a hemoglobin concentration
      between 70 and 110 g/L. The primary endpoint was a composite of diarrhea,
      dysentery, and lower respiratory tract infection episodes (DDL) recorded through
      home visits every 2 d during the intervention and then weekly for 4 mo. The
      noninferiority margin was 1.2. Secondary endpoints included hemoglobin and
      anthropometric changes at 2 and 6 mo. All deaths and hospitalizations were
      documented. To capture seasonal variation, the study was repeated in the winter
      and summer with 2 distinct groups. An intention-to-treat analysis of recurrent
      events was performed by using the univariate Anderson-Gill model. RESULTS: The
      baseline characteristics of the subjects were similar. Analysis of phase
      aggregated DDL data showed that iron MNP was not inferior to PP (relative risk:
      0.81; 95% CI: 0.62, 1.04) and improved hemoglobin concentrations (P < 0.0001). We
      recorded no deaths, and hospitalizations were rare. CONCLUSION: Iron MNP is safe
      and efficacious when provided to children aged 12-24 mo with moderate-to-severe
      malnutrition and anemia. This trial is registered at clinicaltrials.gov as
      NCT00530374.

PMID- 21715513
TI  - Variety and hyperpalatability: are they promoting addictive overeating?

PMID- 21715514
TI  - Effects of vitamin D and calcium supplementation on pancreatic beta cell
      function, insulin sensitivity, and glycemia in adults at high risk of diabetes:
      the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled
      trial.
AB  - BACKGROUND: A suboptimal vitamin D and calcium status has been associated with
      higher risk of type 2 diabetes in observational studies, but evidence from trials
      is lacking. OBJECTIVE: We determined whether vitamin D supplementation, with or
      without calcium, improved glucose homeostasis in adults at high risk of diabetes.
      DESIGN: Ninety-two adults were randomly assigned in a 2-by-2 factorial-design,
      double-masked, placebo-controlled trial to receive either cholecalciferol (2000
      IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk. The primary
      outcome was the change in pancreatic beta cell function as measured by the
      disposition index after an intravenous-glucose-tolerance test. Other outcomes
      were acute insulin response, insulin sensitivity, and measures of glycemia.
      RESULTS: Participants had a mean age of 57 y, a body mass index (BMI; in kg/m(2))
      of 32, and glycated hemoglobin (Hb A(1c)) of 5.9%. There was no significant
      vitamin D * calcium interaction on any outcomes. The disposition index increased
      in the vitamin D group and decreased in the no-vitamin D group (adjusted mean
      change +/- SE: 300 +/- 130 compared with -126 +/- 127, respectively; P = 0.011),
      which was explained by an improvement in insulin secretion (62 +/- 39 compared
      with -36 +/- 37 mU . L(-1) . min, respectively; P = 0.046). Hb A(1c) increased
      less, but nonsignificantly, in the vitamin D group than in the no-vitamin D group
      (0.06 +/- 0.03% compared with 0.14 +/- 0.03%, respectively; P = 0.081). There was
      no significant difference in any outcomes with calcium compared with no calcium.
      CONCLUSION: In adults at risk of type 2 diabetes, short-term supplementation with
      cholecalciferol improved beta cell function and had a marginal effect on
      attenuating the rise in Hb A(1c). This trial was registered at clinicaltrials.gov
      as NCT00436475.

PMID- 21715515
TI  - Zinc: an essential but elusive nutrient.
AB  - Zinc is essential for multiple aspects of metabolism. Physiologic signs of zinc
      depletion are linked with diverse biochemical functions rather than with a
      specific function, which makes it difficult to identify biomarkers of zinc
      nutrition. Nutrients, such as zinc, that are required for general metabolism are
      called type 2 nutrients. Protein and magnesium are examples of other type 2
      nutrients. Type 1 nutrients are required for one or more specific functions:
      examples include iron, vitamin A, iodine, folate, and copper. When dietary zinc
      is insufficient, a marked reduction in endogenous zinc loss occurs immediately to
      conserve the nutrient. If zinc balance is not reestablished, other metabolic
      adjustments occur to mobilize zinc from small body pools. The location of those
      pools is not known, but all cells probably have a small zinc reserve that
      includes zinc bound to metallothionein or zinc stored in the Golgi or in other
      organelles. Plasma zinc is also part of this small zinc pool that is vulnerable
      to insufficient intakes. Plasma zinc concentrations decline rapidly with severe
      deficiencies and more moderately with marginal depletion. Unfortunately, plasma
      zinc concentrations also decrease with a number of conditions (eg, infection,
      trauma, stress, steroid use, after a meal) due to a metabolic redistribution of
      zinc from the plasma to the tissues. This redistribution confounds the
      interpretation of low plasma zinc concentrations. Biomarkers of metabolic zinc
      redistribution are needed to determine whether this redistribution is the cause
      of a low plasma zinc rather than poor nutrition. Measures of metallothionein or
      cellular zinc transporters may fulfill that role.

PMID- 21715516
TI  - Dairy attentuates oxidative and inflammatory stress in metabolic syndrome.
AB  - BACKGROUND: Oxidative and inflammatory stress are elevated in obesity and are
      further augmented in metabolic syndrome. We showed previously that dairy
      components suppress the adipocyte- and macrophage-mediated generation of reactive
      oxygen species and inflammatory cytokines and systemic oxidative and inflammatory
      biomarkers in obesity. OBJECTIVE: The objective of this study was to determine
      the early (7 d) and sustained (4 and 12 wk) effects of adequate-dairy (AD)
      compared with low-dairy (LD) diets in subjects with metabolic syndrome. DESIGN:
      Forty overweight and obese adults with metabolic syndrome were randomly assigned
      to receive AD (3.5 daily servings) or LD (<0.5 daily servings) weight-maintenance
      diets for 12 wk. Oxidative and inflammatory biomarkers were assessed at 0, 1, 4,
      and 12 wk as primary outcomes; body weight and composition were measured at 0, 4,
      and 12 wk as secondary outcomes. RESULTS: AD decreased malondialdehyde and
      oxidized LDL at 7 d (35% and 11%, respectively; P < 0.01), with further decreases
      by 12 wk. Inflammatory markers were suppressed with intake of AD, with decreases
      in tumor necrosis factor-alpha at 7 d and further reductions through 12 wk (35%;
      P < 0.05); decreases in interleukin-6 (21%; P < 0.02) and monocyte
      chemoattractant protein 1 (14% decrease at 4 wk, 24% decrease at 12 wk; P <
      0.05); and a corresponding 55% increase in adiponectin at 12 wk (P < 0.01). LD
      exerted no effect on oxidative or inflammatory markers. Diet had no effect on
      body weight; however, AD significantly reduced waist circumference and trunk fat
      (P < 0.01 for both), and LD exerted no effect. CONCLUSION: An increase in dairy
      intake attenuates oxidative and inflammatory stress in metabolic syndrome. This
      trial was registered at clinicaltrials.gov as NCT01266330.

PMID- 21715517
TI  - Benefits of Renin-Angiotensin blockade on retinopathy in type 1 diabetes vary
      with glycemic control.
AB  - OBJECTIVE: Optimal glycemic control slows diabetic retinopathy (DR) development
      and progression and is the standard of care for type 1 diabetes. However, these
      glycemic goals are difficult to achieve and sustain in clinical practice. The
      Renin Angiotensin System Study (RASS) showed that renin-angiotensin system (RAS)
      blockade can slow DR progression. In the current study, we evaluate whether
      glycemic control influenced the benefit of RAS blockade on DR progression in type
      1 diabetic patients. RESEARCH DESIGN AND METHODS: We used RASS data to analyze
      the relationships between two-steps or more DR progression and baseline glycemic
      levels in 223 normotensive, normoalbuminuric type 1 diabetic patients randomized
      to receive 5 years of enalapril or losartan compared with placebo. RESULTS: A
      total of 147 of 223 patients (65.9%) had DR at baseline (47 of 74 patients
      [63.5%] in placebo and 100 of 149 patients [67.1%] in the combined treatment
      groups [P = 0.67]). Patients with two-steps or more DR progression had higher
      baseline A1C than those without progression (9.4 vs. 8.2%, P < 0.001). There was
      no beneficial effect of RAS blockade (P = 0.92) in patients with baseline A1C
      <=7.5%. In contrast, 30 of 112 (27%) patients on the active treatment arms with
      A1C >7.5% had two-steps or more DR progression compared with 26 of 56 patients
      (46%) in the placebo group (P = 0.03). CONCLUSIONS: RAS blockade reduces DR
      progression in normotensive, normoalbuminuric type 1 diabetic patients with A1C
      >7.5%. Whether this therapy could benefit patients with A1C <=7.5% will require
      long-term studies of much larger cohorts.

PMID- 21715518
TI  - Low estradiol concentrations in men with subnormal testosterone concentrations
      and type 2 diabetes.
AB  - OBJECTIVE: It has been suggested that the high prevalence of subnormal free
      testosterone concentrations, along with low or inappropriately normal
      gonadotropins in men with type 2 diabetes, may be the result of an increase in
      plasma estradiol concentrations secondary to an increase in aromatase activity in
      the adipose tissue that leads to the suppression of the hypothalamo-hypophyseal
      gonadal axis. RESEARCH DESIGN AND METHODS: To investigate this hypothesis, plasma
      estradiol, testosterone, leutinizing hormone, follicle-stimulating hormone, and
      sex hormone-binding globulin (SHBG) concentrations were measured in fasting blood
      samples of 240 men with type 2 diabetes. Free estradiol concentrations were
      either calculated (n = 198) using total estradiol and SHBG measured by
      immunoassay or directly measured by liquid chromatography tandem mass
      spectrometry (LC-MS/MS) and equilibrium dialysis (n = 102). RESULTS: The
      calculated free estradiol concentration in men with subnormal free testosterone
      concentrations was lower than that in men with normal free testosterone
      concentrations (median 0.047 vs. 0.063 ng/dL, P < 0.001). Directly measured (LC
      MS/MS) free estradiol concentrations were also lower in men with subnormal free
      testosterone concentrations (median 0.025 vs. 0.045 ng/dL, P = 0.008). Free
      estradiol concentrations were directly related to free testosterone but not to
      BMI or age. CONCLUSIONS: These data show that the suppression of the hypothalamo
      hypophyseal-gonadal axis in patients with subnormal free testosterone
      concentrations and type 2 diabetes is not associated with increased estradiol
      concentrations. The pathogenesis of subnormal free testosterone concentrations in
      type 2 diabetes needs to be investigated further.

PMID- 21715519
TI  - Biomarkers of renal function and cognitive impairment in patients with diabetes.
AB  - OBJECTIVE: Kidney disease is associated with cognitive impairment in studies of
      nondiabetic adults. We examined the cross-sectional relation between three
      measures of renal function and performance on four measures of cognitive function
      in the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes
      (ACCORD-MIND) study. RESEARCH DESIGN AND METHODS: The relationships among
      estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) (n = 2,968),
      albumin/creatinine ratio (ACR) >=30 MUg/mg (n = 2,957), and cystatin C level >1.0
      mg/L (n = 532) with tertile of performance on the Mini-Mental State Examination,
      Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST),
      and Stroop Test of executive function were measured. RESULTS: In adjusted
      logistic regression models, ACR >=30 MUg/mg was associated with performance in
      the lowest tertile, compared with the highest two tertiles, on the RAVLT (odds
      ratio 1.30, 95% CI 1.09-1.56, P = 0.006), equivalent to 3.6 years of aging, and
      on the DSST (1.47, 1.20-1.80, P = 0.001), equivalent to 3.7 years of aging.
      Cystatin C >1.0 mg/L was borderline associated with the lowest tertile on the
      DSST (1.81, 0.93-3.55, P = 0.08) and Stroop (1.78, 0.97-3.23, P = 0.06) in
      adjusted models. eGFR was not associated with any measure of cognitive
      performance. CONCLUSIONS: In diabetic people with HbA(1c) >7.5% at high risk for
      cardiovascular disease, decreased cognitive function was associated with kidney
      disease as measured by ACR, a measure of microvascular endothelial pathology, and
      cystatin C, a marker of eGFR.

PMID- 21715520
TI  - Effect of case-based training for medical residents on inpatient glycemia.
AB  - OBJECTIVE: To determine whether an educational intervention for medical house
      staff improves blood glucose (BG) in hospitalized patients. RESEARCH DESIGN AND
      METHODS: All 116 medicine residents at an academic medical center were assigned
      to online or classroom training on inpatient dysglycemia in fall 2008. Both
      groups were offered an online refresher course in spring 2009 addressing gaps in
      clinical practice identified on chart review. We assessed event BG, the first BG
      of any 3-h period, on two teaching wards. RESULTS: A total of 108 residents
      (93.1%) completed the initial training. The primary outcome, median event BG,
      decreased from 152 mg/dL in August 2008 to 139 mg/dL in December 2008 (P <
      0.0001). Prevalence of event BG >200 mg/dL decreased from 25.5 to 22.7% (P =
      0.0207), at the expense of more event BGs <70 mg/dL (2.0-3.9%, P = 0.0124).
      CONCLUSIONS: A curriculum for medicine residents on inpatient glycemia led to
      lower inpatient BG.

PMID- 21715521
TI  - Prevalence of diabetes in New York City, 2002-2008: comparing foreign-born South
      Asians and other Asians with U.S.-born whites, blacks, and Hispanics.
AB  - OBJECTIVE: To describe diabetes prevalence in New York City by race/ethnicity and
      nativity. RESEARCH DESIGN AND METHODS: Data were from the New York City 2002-2008
      Community Health Surveys. Respondents were categorized on the basis of self
      reported race/ethnicity and birth country: foreign-born South Asian (Indian
      subcontinent), foreign-born other Asian, U.S.-born non-Hispanic black, U.S.-born
      non-Hispanic white, and U.S.-born Hispanic. Diabetes status was defined by self
      reported provider diagnosis. Multivariable models examined diabetes prevalence by
      race/ethnicity and birth country. RESULTS: Prevalence among foreign-born South
      Asians was nearly twice that of foreign-born other Asians (13.6 vs. 7.4%, P =
      0.001). In multivariable analyses, normal-BMI foreign-born South Asians had
      nearly five times the diabetes prevalence of comparable U.S.-born non-Hispanic
      whites (14.1 vs. 2.9%, P < 0.001) and 2.5 times higher prevalence than foreign
      born other Asians (P < 0.001). CONCLUSIONS: Evaluating Asians as one group masks
      the higher diabetes burden among South Asians. Researchers and clinicians should
      be aware of differences in this population.

PMID- 21715522
TI  - Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin
      using needle-free jet injection technology.
AB  - OBJECTIVE: Insulin administered by jet injectors is dispensed over a larger
      subcutaneous area than insulin injected with a syringe, which may facilitate a
      more rapid absorption. This study compared the pharmacologic profile of
      administration of insulin aspart by jet injection to that by conventional insulin
      pen. RESEARCH DESIGN AND METHODS: Euglycemic glucose clamp tests were performed
      in 18 healthy volunteers after subcutaneous administration of 0.2 units/kg body
      wt of aspart, either administered by jet injection or by conventional pen, using
      a randomized, double-blind, double-dummy, cross over study design.
      Pharmacodynamic and pharmacokinetic profiles were derived from the glucose
      infusion rate (GIR) needed to maintain euglycemia and from plasma insulin levels,
      respectively. RESULTS: The time to maximal GIR was significantly shorter when
      insulin was injected with the jet injector compared with conventional pen
      administration (51 +/- 3 vs. 105 +/- 11 min, P < 0.0001). The time to peak
      insulin concentration was similarly reduced (31 +/- 3 vs. 64 +/- 6 min, P <
      0.0001) and peak insulin concentrations were increased (108 +/- 13 vs. 79 +/- 7
      mU/L, P = 0.01) when insulin was injected by jet injection compared with
      conventional pen injection. Jet injector insulin administration reduced the time
      to 50% glucose disposal by ~40 min (P < 0.0001). There were no differences in
      maximal GIR, total insulin absorption, or total insulin action between the two
      devices. CONCLUSIONS: Administration of insulin aspart by jet injection enhances
      insulin absorption and reduces the duration of glucose-lowering action. This
      profile resembles more closely the pattern of endogenous insulin secretion and
      may help to achieve better meal insulin coverage and correction of postprandial
      glucose excursions.

PMID- 21715523
TI  - Long-term prognostic importance of diabetes after a myocardial infarction depends
      on left ventricular systolic function.
AB  - OBJECTIVE: This study was performed to understand how left ventricular function
      modulates the prognostic importance of diabetes after myocardial infarction (MI).
      RESEARCH DESIGN AND METHODS: Consecutively hospitalized MI patients screened for
      three clinical trials were followed for a median of 7 years. Multivariable Cox
      regression models were used to assess the risk of mortality associated with
      diabetes, and the importance of diabetes was examined independently within
      defined left ventricular ejection fraction (LVEF) subgroups. RESULTS: A total of
      16,912 patients were included; 1,819 (11%) had diabetes. Diabetes and 15% unit
      depression in LVEF were of similar prognostic importance: hazard ratios (HRs)
      were 1.45 (95% CI 1.37-1.54) and 1.41 (1.37-1.45) for diabetes and LVEF
      depression, respectively. LVEF modified the outcomes associated with diabetes,
      with HRs being 1.29 (1.19-1.40) and 1.61 (1.49-1.74) in patients with LVEF <40%
      and LVEF >= 40%, respectively (P = 0.03). CONCLUSIONS: Patients within the higher
      LVEF categories have a greater mortality risk attributable to diabetes than
      patients within the lower LVEF categories.

PMID- 21715524
TI  - Evidence for consistency of the glycation gap in diabetes.
AB  - OBJECTIVE: Discordance between HbA(1c) and fructosamine estimations in the
      assessment of glycemia is often encountered. A number of mechanisms might explain
      such discordance, but whether it is consistent is uncertain. This study aims to
      coanalyze paired glycosylated hemoglobin (HbA(1c))-fructosamine estimations by
      using fructosamine to determine a predicted HbA(1c), to calculate a glycation gap
      (G-gap) and to determine whether the G-gap is consistent over time. RESEARCH
      DESIGN AND METHODS: We included 2,263 individuals with diabetes who had at least
      two paired HbA(1c)-fructosamine estimations that were separated by 10 +/- 8
      months. Of these, 1,217 individuals had a third pair. The G-gap was calculated as
      G-gap = HbA(1c) minus the standardized fructosamine-derived HbA(1c) equivalent
      (FHbA(1c)). The hypothesis that the G-gap would remain consistent in individuals
      over time was tested. RESULTS: The G-gaps were similar in the first, second, and
      third paired samples (0.0 +/- 1.2, 0.0 +/- 1.3, and 0.0 +/- 1.3, respectively).
      Despite significant changes in the HbA(1c) and fructosamine, the G-gap did not
      differ in absolute or relative terms and showed no significant within-subject
      variability. The direction of the G-gap remained consistent. CONCLUSIONS: The G
      gap appears consistent over time; thus, by inference any key underlying
      mechanisms are likely to be consistent. G-gap calculation may be a method of
      exploring and evaluating any such underlying mechanisms.

PMID- 21715525
TI  - Low free testosterone levels are associated with all-cause and cardiovascular
      mortality in postmenopausal diabetic women.
AB  - OBJECTIVE: Hyperandrogenemia is associated with cardiovascular risk factors in
      women but evidence about the relationship of testosterone levels with mortality
      is sparse. We aimed to evaluate whether total testosterone (TT), free
      testosterone (FT), and sex hormone-binding globulin (SHBG) are associated with
      all-cause and cardiovascular mortality in a cohort of postmenopausal women.
      RESEARCH DESIGN AND METHODS: We measured TT and SHBG levels in 875 postmenopausal
      women who were referred for coronary angiography (during 1997-2000). FT was
      calculated according to the Vermeulen method. The main outcome measures were Cox
      proportional hazard ratios (HRs) for mortality from all causes and from
      cardiovascular causes. RESULTS: After a median follow-up time of 7.7 years, 179
      women (20.5%) had died. There were 101 deaths due to cardiovascular disease
      (56.4% of all deaths). We found no association of FT, TT, and SHBG levels with
      mortality in all postmenopausal women. In postmenopausal diabetic women,
      multivariable-adjusted HRs (with 95% CIs) in the fourth compared with the first
      FT quartile for all-cause and cardiovascular mortality were 0.38 (0.08-0.90), P =
      0.025, and 0.28 (0.08-0.90), P = 0.032, respectively. We found no association of
      TT and SHBG with mortality in diabetic postmenopausal women. CONCLUSIONS: In
      postmenopausal diabetic women referred for coronary angiography, low FT levels
      are independently associated with increased all-cause and cardiovascular
      mortality.

PMID- 21715526
TI  - Nuts as a replacement for carbohydrates in the diabetic diet.
AB  - OBJECTIVE: Fat intake, especially monounsaturated fatty acid (MUFA), has been
      liberalized in diabetic diets to preserve HDL cholesterol and improve glycemic
      control, yet the exact sources have not been clearly defined. Therefore, we
      assessed the effect of mixed nut consumption as a source of vegetable fat on
      serum lipids and HbA(1c) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total
      of 117 type 2 diabetic subjects were randomized to one of three treatments for 3
      months. Supplements were provided at 475 kcal per 2,000-kcal diet as mixed nuts
      (75 g/day), muffins, or half portions of both. The primary outcome was change in
      HbA(1c). RESULTS: The relative increase in MUFAs was 8.7% energy on the full-nut
      dose compared with muffins. Using an intention-to-treat analysis (n = 117), full
      nut dose (mean intake 73 g/day) reduced HbA(1c) (-0.21% absolute HbA(1c) units,
      95% CI -0.30 to -0.11, P < 0.001) with no change after half-nut dose or muffin.
      Full-nut dose was significantly different from half-nut dose (P = 0.004) and
      muffin (P = 0.001), but no difference was seen between half-nut dose and muffins.
      LDL cholesterol also decreased significantly after full-nut dose compared with
      muffin. The LDL cholesterol reduction after half-nut dose was intermediate and
      not significantly different from the other treatments. Apolipoprotein (apo) B and
      the apoB:apoA1 ratio behaved similarly. Nut intake related negatively to changes
      in HbA(1c) (r = -0.20, P = 0.033) and LDL cholesterol (r = -0.24, P = 0.011).
      CONCLUSIONS: Two ounces of nuts daily as a replacement for carbohydrate foods
      improved both glycemic control and serum lipids in type 2 diabetes.

PMID- 21715527
TI  - Contribution of antibodies against IA-2beta and zinc transporter 8 to
      classification of diabetes diagnosed under 40 years of age.
AB  - OBJECTIVE: We investigated whether measuring autoantibodies against zinc
      transporter 8 (ZnT8A) and IA-2beta (IA-2betaA) may improve classification of new
      onset type 1 diabetic patients based on detection of autoantibodies against
      insulin (IAA), GAD (GADA), and IA-2 (IA-2A). In addition, we studied the
      correlation of IA-2betaA and ZnT8A with other biological and demographic
      variables. RESEARCH DESIGN AND METHODS: Circulating autoantibodies were
      determined by liquid-phase radiobinding assays from 761 healthy control subjects
      and 655 new-onset (<1 week insulin) diabetic patients (aged 0-39 years) with
      clinical type 1 diabetes phenotype consecutively recruited by the Belgian
      Diabetes Registry. RESULTS: At diagnosis, IA-2betaA and ZnT8A prevalences were 41
      and 58%, respectively. In IAA-negative, GADA-negative, and IA-2A-negative
      patients, one IA-2betaA-positive and eleven ZnT8A-positive individuals were
      identified at the expense of eight and seven additional positive control subjects
      (1%), respectively, for each test. ZnT8A or IA-2betaA screening increased (P <
      0.001; McNemar) the number of patients with >=2 antibodies both under (from 78 to
      87% for ZnT8A and 82% for IA-2betaA) and above age 15 (from 51 to 63% for ZnT8A
      and 56% for IA-2betaA) versus 0% in control subjects. IA-2betaA and ZnT8A were
      preferentially associated with IA-2A, and with younger age at diagnosis. Unlike
      ZnT8A, IA-2betaA levels were positively correlated with HLA-DQ8 and negatively
      with HLA-DQ2. ZnT8A could replace IAA for classification of patients above age 10
      without loss of sensitivity or specificity. CONCLUSIONS: ZnT8A, and to a lesser
      degree IA-2betaA, may usefully complement GADA, IA-2A, and IAA for classifying
      insulin-treated diabetes under age 40 years.

PMID- 21715528
TI  - Profile of two cohorts: UK and US prospective studies of military health.

PMID- 21715529
TI  - Maternal smoking and fetal sex significantly affect metabolic enzyme expression
      in the human fetal liver.
AB  - CONTEXT: Pollutants and toxicants passing from the mother to the fetus may damage
      developing organ systems. The human fetal liver is both a potential target organ
      and a critical defense against exposure to such xenochemicals. OBJECTIVE: The aim
      of the study was to determine the effects of human fetal toxicant exposure, via
      maternal smoking, on metabolic enzyme transcripts in the fetal liver. DESIGN AND
      SETTING: We conducted an observational study of mRNA transcripts and proteins in
      livers from second trimester fetuses at the Universities of Aberdeen and Glasgow.
      PATIENTS/PARTICIPANTS: Liver samples were taken from 55 normal fetuses from women
      undergoing second trimester elective termination. MAIN OUTCOME MEASURES:
      Housekeeping genes for normalization were identified by GeNorm and NormFinder.
      Levels of mRNA transcripts encoding 15 metabolic enzymes and three xenobiotic
      receptors were measured. Expression of representative proteins was shown by
      Western blotting. RESULTS: Eighty-nine percent of measured transcripts were
      detectable in the human fetal liver. Eight transcripts showed significant sex
      specific differences in expression levels (EPHX1, GSTA1, GSTT1, AHR, AS3MT,
      GLRX2, GGT1, CAR). In male fetuses, maternal smoking was associated with a
      decrease in expression of three transcripts (GGT1, CYP2R1, CAR) and an increase
      in eight transcripts (CYP1A1, EPHX1, NQO1, GSTP1, GSTT1, AHR, AS3MT, GLRX2). In
      the female, CYP3A7 and EPHX1 were increased in smoke-exposed fetuses.
      CONCLUSIONS: The human fetal liver expresses a wide array of metabolic enzymes,
      with sex differences apparent in 44% of the transcripts measured. Exposure of the
      fetus to pollutants/toxicants is associated with significantly altered transcript
      expression, with the more marked response in the male potentially affecting
      levels of endogenous factors involved in fetal growth.

PMID- 21715530
TI  - Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy
      subjects.
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) misuse is
      associated with hyponatremia particularly in women. Hyponatremia is possibly due
      to inappropriate secretion of plasma arginine vasopressin (AVP). OBJECTIVE: To
      assess whether MDMA increases plasma AVP and copeptin in healthy male and female
      subjects and whether effects depend on MDMA-induced release of serotonin and
      norepinephrine. Copeptin, the C-terminal part of the AVP precursor
      preprovasopressin, is cosecreted with AVP and can be determined more reliably.
      METHODS: We used a randomized placebo-controlled crossover design. Plasma and
      urine osmolalities as well as AVP and copeptin levels were measured in 16 healthy
      subjects (eight female, eight male) at baseline and after MDMA (125 mg)
      administration. In addition, we tested whether effects of MDMA on AVP and
      copeptin secretion can be prevented by pretreatment with the serotonin and
      norepinephrine transporter inhibitor duloxetine (120 mg), which blocks MDMA
      induced transporter-mediated release of serotonin and norepinephrine. RESULTS:
      MDMA significantly elevated plasma copeptin levels at 60 min and at 120 min
      compared with placebo in women but not in men. The copeptin response to MDMA in
      women was prevented by duloxetine. MDMA also nonsignificantly increased plasma
      AVP levels in women, and the effect was prevented by duloxetine. Although
      subjects drank more water after MDMA compared with placebo administration, MDMA
      tended to increase urine sodium levels and urine osmolality compared with
      placebo, indicating increased renal water retention. CONCLUSION: MDMA increased
      plasma copeptin, a marker for AVP secretion, in women but not in men. This sex
      difference in MDMA-induced AVP secretion may explain why hyponatremia is
      typically reported in female ecstasy users. The copeptin response to MDMA is
      likely mediated via MDMA-induced release of serotonin and/or norepinephrine
      because it was prevented by duloxetine, which blocks the interaction of MDMA with
      the serotonergic and noradrenergic system.

PMID- 21715531
TI  - Long-term high urinary potential renal acid load and low nitrogen excretion
      predict reduced diaphyseal bone mass and bone size in children.
AB  - BACKGROUND: Longitudinal diet assessment data in children suggest bone anabolic
      effects of protein intake and concurrent catabolic effects of dietary acid load.
      However, studies using valid biomarker measurements of corresponding dietary
      intakes are lacking. OBJECTIVE: The aim of the study was to examine whether the
      association of long-term dietary acid load and protein intake with children's
      bone status can be confirmed using approved urinary biomarkers and whether these
      diet influences may be independent of potential bone-anabolic sex steroids.
      METHOD: Urinary nitrogen (uN), urinary net acid excretion (uNAE), and urinary
      potential renal acid load (uPRAL) were quantified in 789 24-h urine samples of
      197 healthy children who had at least three urine collections during the 4 yr
      preceding proximal forearm bone analyses by peripheral quantitative computed
      tomography. uPRAL was determined by subtracting measured mineral cations (sodium
      + potassium + calcium + magnesium) from measured nonbicarbonate anions (chloride
      + phosphorus + sulfate). In a subsample of 167 children, dehydroepiandrosterone
      metabolites were quantified by gas chromatography-mass spectrometry.
      Multivariable regression models adjusted for age, sex, pubertal stage, forearm
      muscle area, forearm length, and urinary calcium were run with uN and/or uPRAL or
      uNAE as predictors. RESULTS: uN was positively associated with bone mineral
      content, cortical area, periosteal circumference, and strength strain index.
      uPRAL (but not uNAE) showed negative associations with bone mineral content and
      cortical area (P < 0.05), both with and without adjustment for the
      dehydroepiandrosterone-derived sex steroid androstenediol. CONCLUSIONS: In line
      with dietary assessment findings, urinary biomarker analyses substantiate long
      term positive effects of protein intake and concomitant negative effects of
      higher dietary acid load on bone status of children, independent of bone-anabolic
      sex steroid action.

PMID- 21715532
TI  - Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid
      disease.
AB  - INTRODUCTION: Antibodies to thyroglobulin (Tg), thyroperoxidase (TPO), and TSH
      receptor (TSH-R) are prevalent in autoimmune thyroid diseases. We aimed to assess
      whether females with Graves disease or Hashimoto thyroiditis are more likely than
      age-matched controls to have thyroid antibodies before clinical diagnosis and to
      measure the timing of antibody seroconversion. METHODS: This was a nested case
      control study using the Department of Defense Serum Repository and the Defense
      Medical Surveillance System, 1998-2007. We assessed thyroid antibodies in the
      serum of 522 female, active-duty, military personnel including: 87 Graves disease
      cases, 87 Hashimoto thyroiditis cases, and 348 age matched controls. One serum
      sample was available at the time of the clinical diagnosis (+/-6 months); three
      additional samples were retrieved from the repository up to 7 yr before the
      clinical diagnosis, for a total of 2088 samples. RESULTS: In Hashimoto
      thyroiditis, TPO antibodies were found in about 66% of the cases at all time
      points. Tg antibodies showed a similar stationary trend, at a lower prevalence of
      about 53%at all time points. No TSH-R antibodies were found. In Graves disease,
      TPO antibodies gradually increased from 31% at 5-7 yr prior to diagnosis to 57%
      at diagnosis and Tg antibodies from 18 to 47%. TSH-R antibodies were present
      before diagnosis and showed an increasing prevalence from 2, 7, 20, to 55%.
      CONCLUSIONS: Antibodies to Tg, TPO, and TSH-R precede by years the development of
      the diagnostic autoimmune thyroid diseases phenotype. Overall, the presence of
      thyroid antibodies in apparently healthy individuals should not be neglected.

PMID- 21715533
TI  - Efficacy of ultrasound-guided percutaneous ethanol injection treatment in
      patients with a limited number of metastatic cervical lymph nodes from papillary
      thyroid carcinoma.
AB  - CONTEXT: Repeated neck explorations can be a difficult task in patients with
      recurrent metastatic cervical lymph nodes from papillary thyroid carcinoma (PTC).
      OBJECTIVE: The aim of this retrospective study has been to assess the efficacy of
      ultrasound (US)-guided percutaneous ethanol injection (PEI) as treatment of
      metastatic cervical lymph nodes from PTC. MATERIALS AND METHODS: Sixty-nine
      patients who previously had undergone thyroidectomy for PTC were selected for
      inclusion. However, three patients were later excluded due to lack of follow-up.
      Lymph node status was determined by US-guided fine-needle aspiration biopsy
      and/or by raised levels of thyroglobulin in washouts from the cytological needle.
      Guided by US, 0.1-1.0 ml of 99.5% ethanol was injected into the metastatic lymph
      nodes. RESULTS: Three patients (eight metastatic lymph nodes in total) were
      reassigned to surgery due to progression (multiple new metastases), leaving 63
      patients and 109 neck lymph nodes to be included. Mean observation time was 38.4
      months (range, 3-72). A total of 101 of the 109 (93%) metastatic lymph nodes
      responded to PEI treatment, 92 (84%) completely and nine incompletely. Two did
      not respond, and four progressed. Two lymph nodes previously considered
      successfully treated showed evidence of malignancy during follow-up. No
      significant side effects were reported. CONCLUSION: US-guided PEI treatment of
      metastatic lymph nodes seems to be an excellent alternative to surgery in
      patients with a limited number of neck metastases from PTC. This procedure should
      replace "berry picking" surgery.

PMID- 21715534
TI  - Stable bone density in HAART-treated individuals with HIV: a meta-analysis.
AB  - CONTEXT: Longitudinal studies of bone mineral density (BMD) in HIV have reported
      conflicting results. OBJECTIVE: We investigated whether temporal changes in BMD
      differ by highly active antiretroviral therapy (HAART) status at baseline. DATA
      SOURCES: Data sources included MEDLINE, EMBASE, and the Web of Science for
      English language studies (1966 to September 2010) and conference abstracts (1997
      2010). STUDY SELECTION: Longitudinal studies reporting BMD at least 48 wk apart
      in adult patients with HIV with a comparable uninfected control group were
      eligible. Uncontrolled studies were included in secondary analyses. DATA
      EXTRACTION: Data were independently extracted by two researchers. DATA SYNTHESIS:
      Data were pooled using random-effects models. In the primary analysis of six
      controlled studies (follow-up 1.5-2.7 yr), there were no significant differences
      in the percent change from baseline in BMD at the total hip or femoral neck
      between HIV cohorts and controls and a decrease of 0.6% (95% confidence interval
      = -1.1 to -0.1) at the spine in the HIV cohorts. In the secondary analysis of 37
      studies (31 uncontrolled, six controlled), cohorts treated with HAART at baseline
      had stable or slight increases in BMD at 1 yr, stable or slight decreases in BMD
      at 2 yr, and stable BMD at 2.5 yr or later. In cohorts that were HAART
      naive/untreated at baseline, there was accelerated loss of BMD at all time
      points, and the annualized rate of BMD change was greatest at 1 yr, but
      thereafter decreased. CONCLUSION: BMD is stable in HIV cohorts established on
      HAART, whereas cohorts initiating HAART have short-term accelerated BMD loss
      followed by a longer period of BMD stability/increases. Routine monitoring of BMD
      in many HAART-treated patients may not be necessary.

PMID- 21715535
TI  - Long-term safety of growth hormone replacement after CNS irradiation.
AB  - CONTEXT: Radiotherapy is a central component in the treatment of many brain
      tumors, but long-term sequelae include GH deficiency and increased risk of
      secondary neoplasms. It is unclear whether replacement therapy with GH (GHRT)
      further increases this risk. OBJECTIVE: The objective of the study was to assess
      the effect of GHRT on the incidence of secondary tumors and tumor recurrence
      after cranial irradiation. DESIGN AND SETTING: We conducted a retrospective
      matched-pairs analysis of previously irradiated patients, with and without GHRT,
      attending a tertiary center between 1994 and 2009. PATIENTS: We reviewed the
      records for all patients undergoing GHRT at our institution over the study
      period. PATIENTS were included if they had received cranial irradiation, GHRT for
      at least 12 months, and records of serial magnetic resonance imaging data and
      data for dose and fractionation of irradiation were available. GH-naive control
      patients were selected from a radiotherapy database of patients attending the
      same hospital. PATIENTS were matched for date of radiotherapy, age, site of
      primary diagnosis, radiation dose, and fractionation. MAIN OUTCOME MEASURE: The
      primary outcome measure was risk of tumor recurrence or secondary tumor. RESULTS:
      Matched controls were identified for 110 GH-treated patients. Median follow-up
      was 14.5 yr. No significant differences were apparent in the number of tumor
      recurrences (six vs. eight, GHRT vs. control group) or secondary tumors (five vs.
      three, respectively) between groups. CONCLUSIONS: Our study demonstrates no
      increased risk for recurrent or secondary neoplasms in patients receiving GHRT,
      thus supporting a high safety profile of GHRT after central nervous system
      irradiation.

PMID- 21715536
TI  - Glycated hemoglobin A1c, fasting plasma glucose, and two-hour postchallenge
      plasma glucose levels in relation to carotid intima-media thickness in chinese
      with normal glucose tolerance.
AB  - CONTEXT: The association between hyperglycemic markers and cardiovascular risk is
      not consistent in nondiabetic subjects. Even less are the data regarding the
      associations in subjects with normal glucose tolerance (NGT). OBJECTIVE: Our
      objective was to assess the association of glycated hemoglobin A1c (HbA1c),
      fasting plasma glucose (FPG), and 2-h postchallenge glucose with carotid intima
      media thickness (CIMT) in subjects with NGT. DESIGN, PARTICIPANTS AND
      MEASUREMENTS: This cross-sectional study included 1627 participants with NGT and
      aged 40 yr and above, who were randomly recruited from Songnan Community, Baoshan
      District, Shanghai. All participants received a 75-g oral glucose tolerance test,
      blood HbA1c assay, and CIMT measurements. RESULTS: Using multivariable linear
      regression, after adjustment for age, sex, smoking and drinking status, body mass
      index, blood pressure, and serum lipids, the increasing trend of CIMT was found
      in HbA1c quartiles (P = 0.016) rather than in FPG and postchallenge glucose
      quartiles. Furthermore, in a fully adjusted logistic model including FPG and
      postchallenge glucose as covariates, participants in the highest quartile of
      HbA1c, as compared with those in the lowest quartile, still conferred a 68%
      increased odds of elevated CIMT (>= 0.70 mm). CONCLUSIONS: In the population of
      NGT, HbA1c is significantly associated with CIMT independent of conventional
      cardiovascular risk factors, FPG, and postchallenge glucose. The results implied
      that HbA1c could be more informative of cardiovascular risk as compared with FPG
      and postchallenge glucose in subjects with NGT.

PMID- 21715537
TI  - Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated
      for thyroid cancer.
AB  - PURPOSE: The purpose of the study was to assess the endocrine effects of
      vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth
      factor receptor, and epidermal growth factor receptor, in 39 patients with
      progressive thyroid cancer included in two randomized placebo-controlled trials
      using vandetanib 300 mg/d. METHODS: Endocrine samplings were performed at
      baseline and then every 6 months. We compared differences in endocrine parameters
      between baseline and on vandetanib therapy or placebo. RESULTS: During vandetanib
      treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D
      (P = 0.001) mean replacement doses were increased; calcium level remained
      unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH
      (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a
      decreased intestinal absorption of vitamin D or lack of sun exposure as a result
      of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain
      serum TSH within the normal range. 3) In male patients, total testosterone (P =
      0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels
      increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P =
      0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P
      = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P =
      0.02), but free urinary cortisol levels remained in the normal range. None of
      these changes were observed in patients randomized to the placebo arm.
      CONCLUSION: In patients with locally advanced or metastatic thyroid cancer, the
      tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid
      hormone, calcium, and vitamin D analog requirements increased, but consequences
      of the biological alterations on phosphocalcic metabolism and gonadotrope and
      adrenal functions are unknown.

PMID- 21715538
TI  - Pituitary carcinoma with malignant growth from first presentation and fulminant
      clinical course--case report and review of the literature.
AB  - CONTEXT: Although pituitary adenomas are common, pituitary carcinoma is a very
      rare condition. OBJECTIVE: We report on a 48-yr-old male presenting with
      pituitary carcinoma with malignant growth from the beginning and a fulminant
      clinical course and give an overview of the previously reported cases, paying
      special attention to clinical and histological parameters that may predict the
      clinical course. METHODS: We performed a MEDLINE search for previously published
      cases of pituitary carcinoma and analyzed the clinical, laboratory, and
      radiological findings. RESULTS: Ki-67 index and the number of metastatic diseases
      found on postmortem examination were significantly increased in patients with no
      treatment response compared to those with some treatment response (P = 0.03 and P
      = 0.02, respectively). In contrast, time to occurrence of metastatic disease and
      time to death were significantly shortened in patients with no treatment response
      (P = 0.01 and P = 0.02, respectively). No differences were found between the two
      groups for gender distribution, tumor size, mitotic activity assessed as the
      number of mitotic figures per 10 high-power fields, and number of locations of
      metastatic disease. CONCLUSION: Frequently relapsing, invasive adenoma should
      raise a suspicion of a malignant disease. Clinically only the presence of
      metastases is a criterion of malignancy. A high Ki-67 index in the pituitary
      carcinoma and early manifestation of metastatic disease appear to predict rapid
      disease progression.

PMID- 21715539
TI  - Thyroid testing during pregnancy at an academic Boston Area Medical Center.
AB  - CONTEXT: Gestational hypothyroidism leads to adverse obstetric outcomes and
      intellectual impairment in offspring. Pregnancy thyroid screening is
      controversial. OBJECTIVE: Our objective was to determine thyroid function testing
      and thyroid dysfunction rates in pregnant women at Boston Medical Center (BMC).
      METHODS: We retrospectively enrolled 1000 pregnant women aged 18-46 yr seen in
      BMC's Obstetrics/Gynecology (OB/GYN) or Family Medicine (FM) Clinics for their
      initial prenatal visit during 2008. Age, race, insurance, gestational age (GA),
      medical history (thyroid or other autoimmune disorders), obstetric history, and
      thyroid function tests were ascertained. RESULTS: A total of 983 women were
      included (17 excluded for coding error). Median maternal age was 28 yr and GA 9.4
      wk. Thyroid testing rates were similar in the 918 (93%) followed by OB/GYN and 65
      (7%) followed by FM (84 vs. 86%). Thirty-nine women had previous thyroid disease,
      of whom 19 took thyroid medications. Four had type 1 diabetes, and nine had other
      autoimmune diseases. Serum TSH was obtained in 832 women (84.6%) at median GA 9.7
      wk (range, 0.1-39.7). The majority were tested during their first trimester
      (65.5%). Of the 832 tested, 56 (6.7%) had trimester-specific elevated TSH, of
      whom nine had a previous history of thyroid disease, two had type 1 diabetes, and
      one had dyschromia. Based on current case-finding guidelines, 45 of 56 women
      (80.4%) with an elevated TSH in pregnancy might not have been tested. CONCLUSION:
      BMC has a high rate of thyroid function testing in pregnancy. Targeted thyroid
      testing in only high-risk patients would have missed 80.4% of pregnant women with
      hypothyroidism.

PMID- 21715540
TI  - The type 2 deiodinase ORFa-Gly3Asp polymorphism (rs12885300) influences the set
      point of the hypothalamus-pituitary-thyroid axis in patients treated for
      differentiated thyroid carcinoma.
AB  - CONTEXT: Iodothyronine deiodinases D1, D2, and D3 play an important role in
      synthesis and degradation of T(3). The relationship between serum TSH and free
      T(4) (FT(4)) levels is determined by an individual set point of the hypothalamus
      pituitary-thyroid axis. OBJECTIVE: Several polymorphisms have been described in
      D1 and D2 of which some are associated with serum TSH and iodothyronine levels.
      In this study we investigate whether polymorphisms of D1 and D2 influence the set
      point of the hypothalamus-pituitary-thyroid axis. DESIGN: We collected 1905 serum
      FT(4) and TSH measurements during 11.5 +/- 8.8 yr of follow-up in patients
      treated for differentiated thyroid carcinoma (DTC). We determined these
      polymorphisms: D1-rs11206244, D1-rs12095080, D2-rs225014, and D2-rs12885300.
      Effects of these polymorphisms on the set points of the hypothalamus-pituitary
      thyroid axis were analyzed with a linear mixed model. SETTING: The study was
      conducted at Leiden University Medical Center, a tertiary referral center for
      DTC. PATIENTS: One hundred fifty-one consecutive patients were treated and cured
      for DTC. MAIN OUTCOME MEASURE: Slopes and intercepts of regression equations
      representing the relationship between InTSH and FT(4) were measured for all
      polymorphisms. RESULTS: DTC patients homozygous for the D2-rs12885300 T allele
      have an altered set point of the hypothalamus-pituitary-thyroid axis. The slope
      of the regression line (corrected for age, body mass index, and gender) for wild
      type patients was -0.32 +/- 0.028 (ln[TSH(mU/liter)]/[FT(4)(pmol/liter)]), the
      intercept, 4.95. For heterozygous patients, the slope was -0.30 +/- 0.028
      (ln[TSH(mU/liter)]/[FT(4)(pmol/liter)]), the intercept, 4.23. The slope of the
      homozygous patients was -0.35 +/- 0.026 (ln[TSH(mU/liter)]/[FT(4)(pmol/liter)])
      and the intercept, 6.07 (P = 0.036 compared with wild-type and heterozygous
      patients). CONCLUSION: Our data suggest that the negative feedback of FT(4) on
      TSH is weaker in patients homozygous for the D2-rs12885300 T allele than in wild
      type and heterozygous subjects.

PMID- 21715541
TI  - Soluble FMS-like tyrosine kinase-1 (sFlt-1) and serum placental growth factor
      (PlGF) as biomarkers for ectopic pregnancy and missed abortion.
AB  - CONTEXT: Diagnosis of early pregnancy failure is hampered by the lack of reliable
      serological markers. OBJECTIVE: We assessed whether a single serum measurement of
      placental growth factor (PlGF) and the soluble Flt-1 (sFlt-1) receptor of
      vascular endothelial growth factor at 6-8 wk gestation could differentiate failed
      pregnancies, whether ectopic pregnancies (EP) or missed abortions (MA), from
      healthy intrauterine pregnancies (IUP). DESIGN AND SETTING: We conducted a
      prospective clinical study at a tertiary university hospital between January 2009
      and February 2011. PATIENTS: A total of 78 consecutive patients (38 EP, 40 MA)
      with failed early pregnancy and 50 IUP (control group) participated in the study.
      INTERVENTION(S): Determination of serum PlGF and sFlt-1 has been carried out by
      ELISA. Gene expression of PlGF and Flt-1 in trophoblasts was performed by RT-PCR.
      MAIN OUTCOME MEASURE(S): We investigated whether a single, combined serum
      measurement of the above markers could contribute to the differential diagnosis.
      RESULTS: PlGF and sFlt-1 concentration was lower in both EP (mean, 14.60 +/-
      3.42/178.16 +/- 76.03 pg/ml) and MA (mean, 16.25 +/- 4.73/399.42 +/- 337.54
      pg/ml) compared to IUP (mean, 21.64 +/- 5.68/1390.32 +/- 655.37 pg/ml). sFlt-1 (P
      = 0.033) and sFlt-1/PlGF ratio (P = 0.029) but not PlGF had the ability to
      discriminate MA from EP. Compared to women with viable IUP, mRNA gene expression
      levels of PlGF and Flt-1 were considerably lower in women with MA and in women
      with EP. CONCLUSIONS: Combined measurement of sFlt-1 and PlGF levels can
      differentiate normal from failed pregnancies, whereas sFlt-1 as well as sFlt
      1/PlGF ratio can also discriminate EP from MA. PlGF and Flt-1 gene expression in
      trophoblasts from women with EP and MA appears impaired.

PMID- 21715542
TI  - Reduction of thyroid nodule volume by levothyroxine and iodine alone and in
      combination: a randomized, placebo-controlled trial.
AB  - CONTEXT: Nodular goiter is common worldwide, but there is still debate over the
      medical treatment. OBJECTIVE: The objective of the study was the measurement of
      the effect of a treatment with (nonsuppressive) T(4), iodine, or a combination of
      both compared with placebo on volume of thyroid nodules and thyroid. DESIGN: This
      was a multicenter, randomized, double-blind trial in patients with nodular goiter
      in Germany [LISA (Levothyroxin und Iodid in der Strumatherapie Als Mono-oder
      Kombinationstherapie) trial]. SETTING: The study was conducted in outpatient
      clinics in university hospitals and regional hospitals and private practices.
      PARTICIPANTS: One thousand twenty-four consecutively screened and centrally
      randomized euthyroid patients aged 18-65 yr with one or more thyroid nodules
      (minimal diameter 10 mm) participated in the study. INTERVENTION: Intervention
      included placebo, iodine (I), T(4), or T(4)+I for 1 yr. T(4) doses were adapted
      for a TSH target range of 0.2-0.8 mU/liter. OUTCOME MEASURES: The primary end
      point was percent volume reduction of all nodules measured by ultrasound, and the
      main secondary end point was a change in goiter volume. RESULTS: Nodule volume
      reductions were -17.3% [95% confidence interval (CI) -24.8/-9.0%, P < 0.001] in
      the T(4)+I group, -7.3% (95% CI -15.0/+1.2%, P = 0.201) in the T(4) group, and 
      4.0% (95% CI -11.4/+4.2%, P = 0.328) in the I group as compared with placebo. In
      direct comparison, the T(4)+I therapy was significantly superior to T(4) (P =
      0.018) or I (P = 0.003). Thyroid volume reductions were -7.9% (95% CI -11.8/
      3.9%, P < 0.001), -5.2% (95% CI -8.7/-1.6%, P = 0.024) and -2.5% (95% CI 
      6.2/+1.4%, P = 0.207), respectively. The T(4)+I therapy was significantly
      superior to I (P = 0.034) but not to T(4) (P = 0.190). CONCLUSION: In a region
      with a sufficient iodine supply, a 1-yr therapy with a combination of I and T(4)
      with incomplete suppression of thyrotropin reduced thyroid nodule volume further
      than either component alone or placebo.

PMID- 21715543
TI  - Identification of estrogen response element in the aquaporin-2 gene that mediates
      estrogen-induced cell migration and invasion in human endometrial carcinoma.
AB  - BACKGROUND: Accumulating evidence suggests that aquaporins (AQP) can facilitate
      cell migration, invasion, and proliferation in tumor development in addition to
      water transport. OBJECTIVE: The aim of this study was to examine AQP2 expression
      in the endometrial tissues from patients with endometrial carcinoma (EC) and
      determine the roles and mechanisms of AQP2 in estrogen-related cell migration,
      invasion, adhesion, and proliferation of Ishikawa (IK) cells. APPROACH: AQP2
      expression levels were measured in human endometrial cells and estradiol (E(2))
      treated IK cells, and the estrogen-response element was identified. After
      blocking down and up-regulating the endogenous expression of AQP2 in IK cells,
      cell morphology, capacity for invasion, migration and adhesion, and expression
      markers of membrane/cytoskeleton were analyzed. RESULTS: AQP2 was expressed in
      endometrial tissues from patients with EC and endometriosis, both of which are
      estrogen-dependent diseases. In IK cells, E(2) dose-dependently increased AQP2
      expression, which was blocked by the estrogen receptor inhibitor ICI182780. An
      estrogen-response element was identified in the AQP2 promoter. E(2) significantly
      increased the migration, invasion, adhesion, and proliferation of IK cells. AQP2
      knockdown attenuated E(2)-enhanced migration, invasion, and adhesion. AQP2
      knockdown reduced not only the E(2)-enhanced expression of F-actin and annexin-2
      but also the E(2)-induced alteration of cell morphology. Moreover, higher
      expression levels of F-actin and annexin-2 were detected in the endometrial
      tissues from patients with EC. CONCLUSIONS: AQP2 mediates E(2)-enhanced
      migration, invasion, and adhesion through alteration of F-actin and annexin-2
      expression and reorganization of F-actin, and inhibition of AQP may be a
      potential method for antitumor therapy.

PMID- 21715544
TI  - Endoscopic transsphenoidal surgery for acromegaly: remission using modern
      criteria, complications, and predictors of outcome.
AB  - CONTEXT: Despite the growing application of endoscopic transsphenoidal surgery
      (ETSS), outcomes for GH adenomas are not clearly defined. OBJECTIVE: We reviewed
      our experience with ETSS with specific interest in remission rates using the 2010
      consensus criteria, predictors of remission, and associated complications. DESIGN
      AND SETTING: This was a retrospective single institution study. PATIENTS,
      INTERVENTIONS, AND OUTCOME MEASURES: Sixty acromegalic patients who underwent
      ETSS were identified. Remission was defined as a normal IGF-I and either a
      suppressed GH less than 0.4 ng/ml during an oral glucose tolerance test or a
      random GH less than 1.0 ng/ml. RESULTS: Remission was achieved in all 14
      microadenomas and 28 of 46 macroadenomas (61%). Tumor size, age, gender, and
      history of prior surgery were not predictive on multivariant analysis. In
      hospital postoperative morning GH levels less than 2.5 ng/ml provided the best
      prediction of remission (P < 0.001). Preoperative variables predictive of
      remission included Knosp score (P = 0.017), IGF-I (P = 0.030), and GH (P = 0.042)
      levels. New endocrinopathy consisted of diabetes insipidus in 5%, adrenal
      insufficiency in 5.4%, and new hypogonadism in 29% of men and 17% of women.
      However, 41% of hypogonadal men had normal postoperative testosterone levels and
      83% of amenorrheic women regained menses. The most common complaints after
      surgery were sinonasal (36 of 60, 60%) resolving in all but two. CONCLUSIONS:
      ETSS for GH adenomas is associated with high rates of remission and a low
      incidence of new endocrinopathy. Despite the panoramic views offered by the
      endoscope, invasive tumors continue to have lower rates of remission.

PMID- 21715545
TI  - Absence of GH-releasing hormone (GHRH) mutations in selected patients with
      isolated GH deficiency.
AB  - CONTEXT: Although numerous reports of mutations in GH1 and GHRHR (GHRH receptor)
      causing isolated GH deficiency (IGHD) have been published, mutations in GHRH
      itself have not been hitherto reported but are obvious candidates for GH
      deficiency. OBJECTIVE: The aim of this study was to identify mutations in GHRH in
      a large cohort of patients with IGHD. PATIENTS AND METHODS: DNA was isolated from
      151 patients diagnosed with IGHD at national and international centers. Seventy
      two patients fulfilled all the following criteria: severe short stature (height
      sd score <= -2.5), low peak GH after stimulation (peak <= 5 ng/ml), eutopic
      posterior pituitary lobe, and absence of mutations in GH1 and GHRHR and therefore
      were strong candidates for GHRH mutations. The coding sequence and splice sites
      of GHRH were amplified by PCR with intronic primers and sequenced. RESULTS: In
      five of 151 patients (four of 42 from Brazil), the GHRH c.223 C>T, p.L75F change
      was identified in heterozygosity. This variant has been previously reported as a
      polymorphism and is more frequent in African than European and Asian populations.
      Six allelic variants (five novel) that do not predict change of amino acids or
      splice sites were identified in five patients: c.147 C>T, p.S49S, IVS1 -70 G>A,
      IVS1 -74 T>C, IVS3 -47 del1, and IVS3 +7 G>A /IVS3+41 G>A. No functional
      mutations were found in this cohort. CONCLUSIONS: GHRH mutations were not
      identified in a selected cohort of patients with IGHD, suggesting that, if they
      exist, they may be an extremely rare cause of IGHD. Other, as-yet-unidentified
      genetic factors may be implicated in the genetic etiology of IGHD in our cohort.

PMID- 21715546
TI  - Effect of the luminance signal on adaptation-based time compression.
AB  - Traditionally, time perception has been considered the product of a central,
      generic, cognitive mechanism. Recent evidence, however, has shown that high
      temporal frequency adaptation induces local reductions in the apparent duration
      of brief intervals suggesting a distributive system with modality-specific
      sensory components. Here, we examine the effect of the luminance signal on these
      adaptation-based temporal distortions. Our results show that the luminance signal
      is crucial to generate duration compression as the effect disappears at
      isoluminance and that low visibility and task difficulty at isoluminance cannot
      explain the discrepancy. We also demonstrate that the effects of adaptation on
      perceived duration are dissociable from those on apparent temporal frequency.
      These results provide further evidence for the involvement of the magnocellular
      system in the neural encoding and representation of visual time.

PMID- 21715547
TI  - Does central coherence relate to the cognitive performance of children with
      autism in dynamic assessments?
AB  - Central coherence refers to an in-built propensity to form meaningful links over
      a wide range of stimuli and to generalize over as wide a range of contexts as
      possible. In children with autism this ability is diminished, and the impact of
      central coherence deficits in children with autism have previously been observed
      using static measures of learning, such as reading comprehension test
      performance. In this study, the relationship between central coherence and more
      dynamic indicators of learning are investigated. The responses of 52 children
      with autism (mean age 9:10 years) on a test of central coherence and a dynamic
      assessment task were analysed. All the children showed significant improvements
      in dynamic assessment test scores after mediation; however, among those with
      below average nonverbal intelligence scores, weak central coherence was
      significantly associated with smaller gains in performance after teaching.
      Implications for the validity of dynamic assessments for children with autism are
      discussed.

PMID- 21715548
TI  - Psychometric properties of the Caregiver Strain Questionnaire (CGSQ) among
      caregivers of children with autism.
AB  - The purpose of this study was to test the psychometric properties of the
      Caregiver Strain Questionnaire (CGSQ) among caregivers of children with autism.
      The CGSQ was originally developed to assess burden experienced by parents of
      children and adolescents with serious emotional and behavioral disorders. Study
      data was collected from 304 primary caregivers of children with autism using a
      cross-sectional survey design. We tested the one-, two-, and three-factor CGSQ
      model. Though the three-factor CGSQ model fit better than the one- and two-factor
      model, it was still short of an acceptable fit. Minor modifications were made to
      the three-factor model by correlating error terms. The modified three-factor CGSQ
      model with correlated error indicated reasonable fit with the data. The 21-item
      CGSQ had good convergent validity, as indicated by the correlation of its three
      subscales with constructs including mental health-related quality of life,
      maladaptive coping, social support, family functioning, and care recipient level
      of functional impairment and extent of behavioral problems, respectively. The
      internal consistency reliability of the instrument was also good, and there were
      no floor and ceiling effects. The CGSQ was found to be a reliable and valid
      instrument to assess burden among caregivers of children with autism.

PMID- 21715549
TI  - Blame and forgiveness judgements among children, adolescents and adults with
      autism.
AB  - We compared the capacity of children, adolescents and adults with and without
      autism to use (a) intent and severity of consequences information for attributing
      blame to an offender, and (b) intent and apologies information for inferring
      willingness to forgive. Participants were presented with two sets of six
      scenarios obtained by combination of intent and severity (or apology)
      information, and instructed to indicate appropriate levels of blame (or
      willingness to forgive). In the blame condition, persons with autism were able to
      consistently use intent information but not to the same degree as their
      comparison counterparts. In the forgiveness condition, intent was not taken into
      account for judging by persons with autism, irrespective of their age.

PMID- 21715550
TI  - A 6.5-cm pseudoaneurysm of the superior mesenteric artery managed by primary
      surgical repair.
AB  - Superior mesenteric artery (SMA) aneurysms are rare but associated with
      significant mortality (25-40%) when complicated by rupture or thrombosis.
      Symptomatic SMA aneurysms, asymptomatic aneurysms of >=2 cm size and
      pseudoaneurysms need intervention. We report a case of a 6.5-cm symptomatic SMA
      aneurysm managed by open surgical repair. At intraoperative exploration, the
      aneurysm was recognized to be a pseudoaneurysm with a narrow neck (1 mm defect in
      the native vessel) and was dealt by primary repair. Clinical presentation, the
      role of radiological investigations and management are discussed. Detailed
      preoperative assessment of the anatomical characters is essential in planning the
      intervention for SMA aneurysms. The required information can be obtained by
      selective interventional angiogram or computed tomographic angiogram with three
      dimensional reconstruction. Multi-institutional prospective databases might
      provide better evidence regarding the timing of intervention, treatment modality,
      postinterventional follow-up and surveillance of patients with mesenteric
      aneurysms.

PMID- 21715551
TI  - Cystic adventitial disease of the popliteal artery.
AB  - Cystic adventitial disease (CAD) is a rare condition caused by a cystic
      abnormality of the adventitia. It is most commonly found in young or middle-aged
      adults without significant risk factors for peripheral arterial disease. The
      disease usually affects the popliteal artery and can present with intermittent
      claudication. We present a case of CAD of the popliteal artery in a 65-year-old
      man and describe its treatment. For symptomatic patients, treatment of choice
      remains surgical resection of the cyst through a posterior approach.

PMID- 21715552
TI  - Clostridium septicum post-endovascular aneurysm repair stent-graft infection.
AB  - Endovascular aortic aneurysm repair (EVAR) is establishing its role as a valid
      alternative for the treatment of abdominal aortic aneurysm. Post-EVAR graft
      infection is a rare and devastating complication. The incidence of post-EVAR
      graft infection is yet to be defined, and available data at this stage consist of
      case reports and small series. Possible etiologies for aortic stent-graft
      infection include perioperative contamination and hematogenous seeding. To the
      best of our knowledge, this is the first report of post-EVAR stent graft
      infection with Clostridium septicum. The possible mechanisms of this unusual
      hematogenous seeding have been discussed.

PMID- 21715553
TI  - NOD1 activators link innate immunity to insulin resistance.
AB  - OBJECTIVE: Insulin resistance associates with chronic inflammation, and
      participatory elements of the immune system are emerging. We hypothesized that
      bacterial elements acting on distinct intracellular pattern recognition receptors
      of the innate immune system, such as bacterial peptidoglycan (PGN) acting on
      nucleotide oligomerization domain (NOD) proteins, contribute to insulin
      resistance. RESEARCH DESIGN AND METHODS: Metabolic and inflammatory properties
      were assessed in wild-type (WT) and NOD1/2(-/-) double knockout mice fed a high
      fat diet (HFD) for 16 weeks. Insulin resistance was measured by hyperinsulinemic
      euglycemic clamps in mice injected with mimetics of meso-diaminopimelic acid
      containing PGN or the minimal bioactive PGN motif, which activate NOD1 and NOD2,
      respectively. Systemic and tissue-specific inflammation was assessed using enzyme
      linked immunosorbent assays in NOD ligand-injected mice. Cytokine secretion,
      glucose uptake, and insulin signaling were assessed in adipocytes and primary
      hepatocytes exposed to NOD ligands in vitro. RESULTS: NOD1/2(-/-) mice were
      protected from HFD-induced inflammation, lipid accumulation, and peripheral
      insulin intolerance. Conversely, direct activation of NOD1 protein caused insulin
      resistance. NOD1 ligands induced peripheral and hepatic insulin resistance within
      6 h in WT, but not NOD1(-/-), mice. NOD2 ligands only modestly reduced peripheral
      glucose disposal. NOD1 ligand elicited minor changes in circulating
      proinflammatory mediators, yet caused adipose tissue inflammation and insulin
      resistance of muscle AS160 and liver FOXO1. Ex vivo, NOD1 ligand caused
      proinflammatory cytokine secretion and impaired insulin-stimulated glucose uptake
      directly in adipocytes. NOD1 ligand also caused inflammation and insulin
      resistance directly in primary hepatocytes from WT, but not NOD1(-/-), mice.
      CONCLUSIONS: We identify NOD proteins as innate immune components that are
      involved in diet-induced inflammation and insulin intolerance. Acute activation
      of NOD proteins by mimetics of bacterial PGNs causes whole-body insulin
      resistance, bolstering the concept that innate immune responses to distinctive
      bacterial cues directly lead to insulin resistance. Hence, NOD1 is a plausible,
      new link between innate immunity and metabolism.

PMID- 21715554
TI  - Superoxide production by macrophages and T cells is critical for the induction of
      autoreactivity and type 1 diabetes.
AB  - OBJECTIVE: The role of reactive oxygen species (ROS) and their dissipation in
      type 1 diabetes pathogenesis have garnered considerable controversy. Our recent
      work has demonstrated the importance of NADPH oxidase (NOX) activity for type 1
      diabetes development and modulating T-cell autoreactivity. We previously linked
      decreased monocyte ROS with diabetes resistance in the alloxan-resistant mouse,
      and NOD-Ncf1(m1J) mice with a genetic ablation of NOX activity had reduced and
      delayed type 1 diabetes compared with NOD mice. RESEARCH DESIGN AND METHODS: To
      determine the required cellular sources of ROS that are necessary for type 1
      diabetes initiation, we used antibody depletion and adoptive transfer experiments
      into NOD and NOD-Scid females, respectively. After receiving treatment, female
      mice were monitored for hyperglycemia and overt diabetes. RESULTS: Depletion of
      macrophages and neutrophils fully protected NOD mice from type 1 diabetes.
      However, elimination of neutrophils alone showed no significant reduction or
      delay. Type 1 diabetes induction in NOD-Scid mice by adoptive transfer with NOD
      Ncf1(m1J) splenocytes was significantly delayed compared with NOD splenocytes,
      suggesting macrophage ROS and modulation of effector responses are critical for
      diabetes. The adaptive immune response was also altered by the absence of NOX
      activity, as purified T cells from NOD-Ncf1(m1J) mice exhibited delayed transfer
      kinetics. Cotransfer experiments demonstrated the defect was intrinsic to NOX
      deficient CD8(+) T cells. After stimulation, cytotoxic T cells exhibited
      decreased effector function in the absence of superoxide production. CONCLUSIONS:
      These data demonstrate that the impaired autoreactive response of NOX-deficient
      NOD-Ncf1(m1J) immune system results from an alteration in the antigen-presenting
      cell-T-cell axis rather than failure of neutrophils to act as effector cells and
      that ROS signaling is important for the initiation of beta-cell-directed
      autoimmunity by T cells.

PMID- 21715555
TI  - Uncoupling of proliferation and cytokines from suppression within the
      CD4+CD25+Foxp3+ T-cell compartment in the 1st year of human type 1 diabetes.
AB  - OBJECTIVE: The mechanistic basis for the breakdown of T-cell tolerance in type 1
      diabetes is unclear and could result from a gain of effector function and/or loss
      of regulatory function. In humans, the CD4+CD25+Foxp3+ T-cell compartment
      contains both effector and regulatory T cells, and it is not known how their
      relative proportions vary in disease states. RESEARCH DESIGN AND METHODS: We
      performed a longitudinal study of CD4+CD25+ T-cell function in children with type
      1 diabetes at onset and throughout the 1st year of disease. Function was assessed
      using single-cell assays of proliferation, cytokine production, and suppression.
      Type 1 diabetic individuals were compared with age-matched control subjects, and
      suppression was directly assessed by coculture with control T-cell targets.
      RESULTS: We identify novel functional changes within the type 1 diabetes
      CD4+CD25+ compartment. Type 1 diabetic CD4+CD25+ cells exhibited a striking
      increase in proliferative capacity in coculture with CD4 T cells that was present
      at onset and stable 9-12 months from diagnosis. Elevated type 1 diabetes
      CD4+CD25+ cell proliferation correlated with increased inflammatory cytokines
      interleukin 17 and tumor necrosis factor-alpha but not gamma-interferon. Type 1
      diabetes CD4+CD25+ cytokine production occurred coincident with suppression of
      the same cytokines in the control targets. Indeed, enhanced
      proliferation/cytokines by CD4+CD25+ cells was uncoupled from their suppressive
      ability. Longitudinally, we observed a transient defect in type 1 diabetes
      CD4+CD25+ suppression that unexpectedly correlated with measures of improved
      metabolic function. CONCLUSIONS: Type 1 diabetes onset, and its subsequent
      remission period, is associated with two independent functional changes within
      the CD4+CD25+ T-cell compartment: a stable increase in effector function and a
      transient decrease in regulatory T-cell suppression.

PMID- 21715556
TI  - Putting genetic interactions in context through a global modular decomposition.
AB  - Genetic interactions provide a powerful perspective into gene function, but our
      knowledge of the specific mechanisms that give rise to these interactions is
      still relatively limited. The availability of a global genetic interaction map in
      Saccharomyces cerevisiae, covering ~30% of all possible double mutant
      combinations, provides an unprecedented opportunity for an unbiased assessment of
      the native structure within genetic interaction networks and how it relates to
      gene function and modular organization. Toward this end, we developed a data
      mining approach to exhaustively discover all block structures within this
      network, which allowed for its complete modular decomposition. The resulting
      modular structures revealed the importance of the context of individual genetic
      interactions in their interpretation and revealed distinct trends among genetic
      interaction hubs as well as insights into the evolution of duplicate genes. Block
      membership also revealed a surprising degree of multifunctionality across the
      yeast genome and enabled a novel association of VIP1 and IPK1 with DNA
      replication and repair, which is supported by experimental evidence. Our modular
      decomposition also provided a basis for testing the between-pathway model of
      negative genetic interactions and within-pathway model of positive genetic
      interactions. While we find that most modular structures involving negative
      genetic interactions fit the between-pathway model, we found that current models
      for positive genetic interactions fail to explain 80% of the modular structures
      detected. We also find differences between the modular structures of essential
      and nonessential genes.

PMID- 21715557
TI  - Determinants of patient satisfaction: a study among 39 hospitals in an in-patient
      setting in Germany.
AB  - OBJECTIVE: To identify key determinants of patient satisfaction. DESIGN: Data
      used were obtained through a self-administered, post-visit questionnaire by
      random sampling during the period of January 2009 to September 2009. SETTING:
      Thirty-nine hospitals in Germany. PARTICIPANTS: A total of 8,428 patients. MAIN
      OUTCOME MEASURE: Global patient satisfaction was measured by a single item
      question. Attributes of medical aspects of care were measured using 12 items,
      performance of service using 3 items and different dimensions of patient
      expectations using 12 items. Medical aspects of care and performance of service
      items were entered into logistic regression analysis to identify determinants of
      patient satisfaction. RESULTS: The results of the analysis showed that there are
      10 determinants of global patient satisfaction. The outcome of treatment was
      overall, the most salient predictor followed by nursing kindness as the second
      most important component. Items reflecting information receiving about the
      undergoing treatment do not have a major influence on patient satisfaction.
      CONCLUSION: The analysis identified key determinants that should be altered first
      in order to improve global patient satisfaction. The results also indicate that
      some aspects of the hospital stay are not seen as relevant by patients and
      therefore are unrelated to satisfaction ratings. The findings suggest that
      variables measuring patients' perceptions of care are more important determinants
      of global patient satisfaction in comparison to demographics and visit
      characteristics. Results of the present study have implications for health
      providers aiming at improving the service quality and quality of care.

PMID- 21715558
TI  - A population-based survey using PPE-15: relationship of care aspects to patient
      satisfaction in Hong Kong.
AB  - OBJECTIVE: Satisfaction with hospitalization may lead to both better health
      outcomes for patients and create better working environment and relationship
      between staff and patients. The objective of this study is to explore the
      relationship between the experiences of inpatients with specific aspects of care
      and satisfaction with the hospitalization experience. DESIGN: A secondary data
      analysis based on the Thematic Household Survey which was regularly conducted by
      the Census and Statistic Department. SETTING: This survey covered the land-based
      non-institutional population of the Hong Kong Special Administrative Region
      (HKSAR), China, and representing 99% of the total population of HKSAR of 6.8
      million. PARTICIPANTS: Totally 1264 respondents aged >=15 who had ever been
      admitted to local hospital in 12 months prior enumeration were recruited. MAIN
      OUTCOME MEASURES: The Picker Patient Experience Questionnaire-15 (PPE-15) was
      adopted for measuring patient-perceived quality of hospitalization; and one
      global rating of the overall quality of hospital service was included. RESULTS:
      The mean global satisfaction scores for public and private hospital care were
      7.3/10 and 7.8/10, respectively. By adjusting patient demographics, the
      regression models show that 'want to be more involved in decision made about the
      care and treatment', 'respect for patient's dignity', 'patients' family have
      enough opportunity to talk to doctor' and 'tell about danger signals regarding
      illness/treatment after went home' are major determinants of the global
      satisfaction scores. CONCLUSION: Communication, respect and patient engagement in
      provider-patient relationship are important in determining patient's
      satisfaction. Training and healthcare education curriculum could take this into
      account for ensuring the quality of patient-centered care.

PMID- 21715559
TI  - Nitric oxide coordinates metabolism, growth, and development via the nuclear
      receptor E75.
AB  - Nitric oxide gas acts as a short-range signaling molecule in a vast array of
      important physiological processes, many of which include major changes in gene
      expression. How these genomic responses are induced, however, is poorly
      understood. Here, using genetic and chemical manipulations, we show that nitric
      oxide is produced in the Drosophila prothoracic gland, where it acts via the
      nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to
      interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3).
      Manipulation of these interactions leads to gross alterations in feeding
      behavior, fat deposition, and developmental timing. These neuroendocrine
      interactions and consequences appear to be conserved in vertebrates.

PMID- 21715560
TI  - The relative ratio of condensin I to II determines chromosome shapes.
AB  - To understand how chromosome shapes are determined by actions of condensins and
      cohesin, we devised a series of protocols in which their levels are precisely
      changed in Xenopus egg extracts. When the relative ratio of condensin I to II is
      forced to be smaller, embryonic chromosomes become shorter and thicker, being
      reminiscent of somatic chromosomes. Further depletion of condensin II unveils its
      contribution to axial shortening of chromosomes. Cohesin helps juxtapose sister
      chromatid arms by collaborating with condensin I and counteracting condensin II.
      Thus, chromosome shaping is achieved by an exquisite balance among condensin I
      and II and cohesin.

PMID- 21715561
TI  - Afobazole modulates microglial function via activation of both sigma-1 and sigma
      2 receptors.
AB  - Microglial cells play a critical role in the neuroinflammatory response that
      accompanies various diseases of the central nervous system, such as ischemic
      stroke, and ATP is a major signaling molecule regulating the response of these
      cells to these pathophysiological conditions. Experiments were carried out to
      determine the effects of afobazole on microglial function and to identify the
      molecular mechanisms by which afobazole affects microglial cells. Afobazole was
      found to inhibit migration of microglial cells in response to ATP and UTP
      chemoattraction in a concentration-dependent manner. Inhibition of either sigma-1
      or sigma-2 receptors decreased the effects of afobazole on microglia. In addition
      to inhibiting microglial cell migration, activation of sigma receptors by
      afobazole decreased intracellular calcium elevation produced by focal application
      of ATP and UTP in isolated microglial cells. Furthermore, afobazole blocked
      membrane currents elicited by rapid application of ATP in microglial cells. Taken
      together, our data indicate that afobazole inhibits microglial response to P2Y
      and P2X purinergic receptor activation by functioning as a pan-selective sigma
      receptor agonist. In addition to modulating response to purinergic receptor
      activation, the effects of afobazole on microglial survival during in vitro
      ischemia were assessed. Application of afobazole during in vitro ischemia
      decreased microglial cell death during the ischemic episode and after a 24-h
      recovery period. Moreover, when afobazole was only applied after the ischemic
      episode, a significant enhancement in cell survival was still observed. Thus,
      afobazole acts via sigma receptors to decrease microglial response to ATP and
      provides cytoprotection during and after ischemia.

PMID- 21715562
TI  - Afobazole modulates neuronal response to ischemia and acidosis via activation of
      sigma-1 receptors.
AB  - Afobazole is an anxiolytic medication that has been previously shown to be
      neuroprotective both in vitro and in vivo. However, the mechanism(s) by which
      afobazole can enhance neuronal survival remain poorly understood. Experiments
      were carried out to determine whether afobazole can decrease intracellular
      calcium overload associated with ischemia and acidosis and whether the effects of
      afobazole are mediated via interaction of the compound with sigma receptors.
      Fluorometric Ca(2+) imaging was used to resolve how application of afobazole
      affects intracellular Ca(2+) handling in cortical neurons. Application of
      afobazole significantly depressed, in a concentration-dependent and reversible
      manner, the intracellular Ca(2+) overload resulting from in vitro ischemia and
      acidosis. The IC(50) for afobazole inhibition of ischemia-evoked intracellular
      Ca(2+) overload was considerably less than that for the inhibition of [Ca(2+)](i)
      increases induced by acidosis. However, afobazole maximally inhibited only 70% of
      the ischemia-evoked intracellular Ca(2+) overload but effectively abolished
      intracellular Ca(2+) increases produced by acidosis. The effects of afobazole on
      ischemia- and acidosis-induced intracellular Ca(2+) dysregulation were inhibited
      by preincubating the neurons in the irreversible, pan-selective sigma-receptor
      antagonist, metaphit. Moreover, the effects of afobazole on intracellular Ca(2+)
      increases triggered by acidosis and ischemia were blocked by the selective sigma
      1-receptor antagonists, BD 1063 and BD 1047, respectively. Experiments examining
      the effects of afobazole on neuronal survival in response to ischemia showed that
      afobazole was neuroprotective. Taken together, these data suggest that afobazole
      regulates intracellular Ca(2+) overload during ischemia and acidosis via
      activation of sigma-1 receptors. This mechanism is probably responsible for
      afobazole-mediated neuroprotection.

PMID- 21715563
TI  - Adenosine-to-inosine RNA editing meets cancer.
AB  - The role of epigenetics in tumor onset and progression has been extensively
      addressed. Discoveries in the last decade completely changed our view on RNA. We
      now realize that its diversity lies at the base of biological complexity.
      Adenosine-to-inosine (A-to-I) RNA editing emerges a central generator of
      transcriptome diversity and regulation in higher eukaryotes. It is the
      posttranscriptional deamination of adenosine to inosine in double-stranded RNA
      catalyzed by enzymes of the adenosine deaminase acting on RNA (ADAR) family.
      Thought at first to be restricted to coding regions of only a few genes, recent
      bioinformatic analyses fueled by high-throughput sequencing revealed that it is a
      widespread modification affecting mostly non-coding repetitive elements in
      thousands of genes. The rise in scope is accompanied by discovery of a growing
      repertoire of functions based on differential decoding of inosine by the various
      cellular machineries: when recognized as guanosine, it can lead to protein
      recoding, alternative splicing or altered microRNA specificity; when recognized
      by inosine-binding proteins, it can result in nuclear retention of the transcript
      or its degradation. An imbalance in expression of ADAR enzymes with consequent
      editing dysregulation is a characteristic of human cancers. These alterations may
      be responsible for activating proto-oncogenes or inactivating tumor suppressors.
      While unlikely to be an early initiating 'hit', editing dysregulation seems to
      contribute to tumor progression and thus should be considered a 'driver
      mutation'. In this review, we examine the contribution of A-to-I RNA editing to
      carcinogenesis.

PMID- 21715564
TI  - VHL gene mutations and their effects on hypoxia inducible factor HIFalpha:
      identification of potential driver and passenger mutations.
AB  - Mutations of the von Hippel-Lindau (VHL) gene are frequent in clear cell renal
      cell carcinomas (ccRCC). Nonsense and frameshift mutations abrogate the function
      of the VHL protein (pVHL), whereas missense mutations can have different effects.
      To identify those missense mutations with functional consequences, we sequenced
      VHL in 256 sporadic ccRCC and identified 187 different VHL mutations of which 65
      were missense mutations. Location and destabilizing effects of VHL missense
      mutations were determined in silico. The majority of the thermodynamically
      destabilizing missense mutations were located in exon 1 in the core of pVHL,
      whereas protein surface mutations in exon 3 affected the interaction domains of
      elongin B and C. Their impact on pVHL's functionality was further investigated in
      vitro by stably reintroducing VHL missense mutations into a VHL null cell line
      and by monitoring the green fluorescent protein (GFP) signals after the
      transfection of a hypoxia inducible factor (HIF)alpha-GFP expression vector.
      pVHL's functionality ranged from no effect to complete HIF stabilization.
      Interestingly, Asn78Ser, Asp121Tyr, and Val130Phe selectively influenced
      HIF1alpha and HIF2alpha degradation. In summary, we obtained three different
      groups of missense mutations: one with severe destabilization of pVHL; a second
      without destabilizing effects on pVHL but relevance for the interaction with
      HIFalpha, elongin B, and elongin C; and a third with pVHL functions comparable
      with wild type. We therefore conclude that the specific impact of missense
      mutations may help to distinguish between driver and passenger mutations and may
      explain responses of ccRCC patients to HIF-targeted therapies.

PMID- 21715565
TI  - Maximal T cell-mediated antitumor responses rely upon CCR5 expression in both
      CD4(+) and CD8(+) T cells.
AB  - Immune responses against cancer rely upon leukocyte trafficking patterns that are
      coordinated by chemokines. CCR5, the receptor for chemotactic chemokines
      MIP1alpha, MIP1beta, and RANTES (CCL3, CCL4, CCL5), exerts major regulatory
      effects on CD4(+)- and CD8(+) T cell-mediated immunity. Although CCR5 and its
      ligands participate in the response to various pathogens, its relevance to
      tumoral immune control has been debated. Here, we report that CCR5 has a
      specific, ligand-dependent role in optimizing antitumor responses. In adoptive
      transfer studies, efficient tumor rejection required CCR5 expression by both
      CD4(+) and CD8(+) T cells. CCR5 activation in CD4(+) cells resulted in CD40L
      upregulation, leading to full maturation of antigen-presenting cells and enhanced
      CD8(+) T-cell crosspriming and tumor infiltration. CCR5 reduced chemical-induced
      fibrosarcoma incidence and growth, but did not affect the onset or progression of
      spontaneous breast cancers in tolerogenic Tg(MMTV-neu) mice. However, CCR5 was
      required for TLR9-mediated reactivation of antineu responses in these mice. Our
      results indicate that CCR5 boosts T-cell responses to tumors by modulating helper
      dependent CD8(+) T-cell activation.

PMID- 21715566
TI  - CMF revisited in the 21st century.
AB  - Over the last 35 years, classical CMF (combination chemotherapy with
      cyclophosphamide, methotrexate and fluorouracil) has been a milestone in the
      adjuvant treatment of women with breast cancer. However, after an early burst of
      success lasted just over 10 years, classical CMF has been supplanted by 'third
      generation' regimens containing taxanes and anthracyclines. Questions have been
      raised in the past years concerning the true effectiveness of adjuvant CMF for
      specific subgroups of patients and particularly, recent retrospective data
      support the fact that the CMF might have a role in the treatment of patients with
      triple-negative breast cancer. One possible justification for supporting this
      role of CMF may be sought in the mechanism of action of drugs used in the
      regimen, as triple-negative cells may be sensitive to alkylating agents that
      cause double-strand breaks in DNA. The lesson learned from the CMF could lead us
      to identify new combinations of drugs that could include the optimal chemotherapy
      backbone for triple-negative breast cancer such as platinum compounds or
      alkylating agents or Poly (ADP-ribose) polymerase inhibitors. In conclusion,
      although we have learned a lot from the use of CMF, many questions are still open
      and hopefully stimulate our thinking, as clinicians, leading us to find new and
      more effective ways to treat breast cancer.

PMID- 21715567
TI  - Regression of glioma in rat models by intranasal application of parvovirus h-1.
AB  - PURPOSE: In previous studies, we have shown that the apathogenic rat parvovirus H
      1 (H-1PV) is capable to induce regression of advanced symptomatic rat and human
      gliomas in a rat model, when the virus was injected in the tumor (intracranially)
      or intravenously. Infection with H-1PV did not provoke any pathology in nontumor
      tissue. This study addresses the question whether also intranasal application of
      this oncolytic virus is suitable and sufficient for treating gliomas in this
      animal model. EXPERIMENTAL DESIGN: Rat (RG-2) or human (U87) glioma cells were
      grafted stereotactically in the brain of rats (Wistar or RNU, respectively), and
      after development of tumors visible by MRI, H-1PV was instilled intranasally.
      Tumor regression was monitored by MRI, and survival was analyzed by Kaplan-Meier
      analysis. Brains from sacrificed animals were analyzed for histologic
      alterations, presence of viral DNA and proteins and infectious virions. In
      addition, distribution of virus to other organs was determined. RESULTS: A single
      intranasal instillation of H-1PV was sufficient to induce efficient regression of
      rat glioma, leading to significant prolongation of survival without any toxicity
      for other tissues. It is shown that the virus reaches brain and other tissues,
      and that the viral replication-associated (and oncolysis-associated) regulatory
      proteins are exclusively expressed in the tumor tissue. In rats with xenografts
      of human glioma, oncolytic activity of H-1PV was less pronounced, however,
      leading to significant prolongation of survival. CONCLUSION: In view of an
      ongoing clinical trial on the use of H-1PV for oncolytic virotherapy of glioma,
      the option of applying the virus intranasally may be a valuable alternative to
      invasive routes of infection.

PMID- 21715568
TI  - Effective targeting of triple-negative breast cancer cells by PF-4942847, a novel
      oral inhibitor of Hsp 90.
AB  - PURPOSE: Triple-negative breast cancer (TNBC) patients have poor prognoses and
      survival outcomes such that the development of new targeted therapies is in
      strong demand. Mechanisms associated with high proliferation and aggressive tumor
      progression, such as PI3K/PTEN aberration, epidermal growth factor receptor
      (EGFR) overexpression, and cell-cycle upregulation, play important roles in TNBC.
      The molecular chaperone Hsp90 is required for the conformational maturation and
      stability of a variety of proteins in multiple pathways, such as EGFR, AKT, Raf,
      cdk4, etc. Therefore, an Hsp90 inhibitor may show therapeutic benefit in TNBC by
      targeting multiple pathways. EXPERIMENTAL DESIGN: The novel oral Hsp90 inhibitor
      PF-4942847 was characterized in multiple in vitro and in vivo assays to determine
      its antitumor activity in TNBC cell lines. In addition, the correlation of AKT
      degradation and Hsp70 induction in host peripheral blood lymphocytes (PBL) and
      xenograft tumors was determined. RESULTS: PF-4942847 induces degradation of
      multiple client proteins, cell-cycle block, apoptosis, and inhibits cell
      proliferation in TNBC lines, subsequently leading to tumor growth inhibition in
      mouse xenograft models. The correlation of AKT degradation and Hsp70 induction
      between PBLs and xenograft tumors reveals a differential modulation of Hsp90
      activity between host and tumor tissues, and suggests that AKT degradation in
      PBLs may serve as a pharmacodynamic biomarker in future clinical development.
      CONCLUSIONS: The novel oral Hsp90 inhibitor, PF-4942847, is a candidate for
      clinical development in TNBC by collaboratively targeting multiple signaling
      pathways. In addition, AKT degradation in PBLs may serve as a biomarker in
      clinical development.

PMID- 21715569
TI  - Adaptive potential of northernmost tree populations to climate change, with
      emphasis on Scots pine (Pinus sylvestris L.).
AB  - The adaptive potential of the northernmost Pinus sylvestris L. (and other
      northern tree) populations is considered by examining first the current patterns
      of quantitative genetic adaptive traits, which show high population
      differentiation and clines. We then consider the postglacial history of the
      populations using both paleobiological and genetic data. The current patterns of
      diversity at nuclear genes suggest that the traces of admixture are mostly
      visible in mitochondrial DNA variation patterns. There is little evidence of
      increased diversity due to admixture between an eastern and western colonization
      lineage, but no signal of reduced diversity (due to sequential bottlenecks)
      either. Quantitative trait variation in the north is not associated with the
      colonizing lineages. The current clines arose rapidly and may be based on
      standing genetic variation. The initial phenotypic response of Scots pine in the
      north is predicted to be increased survival and growth. The genetic responses are
      examined based on quantitative genetic predictions of sustained selection
      response and compared with earlier simulation results that have aimed at more
      ecological realism. The phenotypic responses of increased growth and survival
      reduce the opportunity for selection and delay the evolutionary responses. The
      lengthening of the thermal growing period also causes selection on the critical
      photoperiod in the different populations. Future studies should aim at including
      multiple ecological and genetic factors in evaluating potential responses.

PMID- 21715570
TI  - DNA damage and DNA damage response in human bronchial epithelial BEAS-2B cells
      following exposure to 2-nitrobenzanthrone and 3-nitrobenzanthrone: role in
      apoptosis.
AB  - Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are mutagenic and
      carcinogenic environmental pollutants found in diesel exhaust and on urban air
      pollution particles. In the present study, human bronchial epithelial BEAS-2B
      cells were exposed to 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3
      NBA). DNA damage responses were compared to those observed after exposure to 1
      nitropyrene (1-NP) and benzo[a]pyrene (B[a]P). Examination by microscopy revealed
      that 3-NBA was the most potent toxic compound while weaker responses were
      observed with 1-NP and B[a]P. Most interestingly, 2-NBA did not induce cell death
      or any other stress-related responses. 3-NBA induced a typical apoptotic cell
      death judged by nuclear condensation and little plasma membrane damage as well as
      cleavage of caspase 3 and poly-(ADP-ribose) polymerase (PARP). Exposure to 3-NBA
      resulted in an accumulation of cells in S-phase, and further analysis by Western
      blotting, immunocytochemistry and flow cytometry revealed that 3-NBA induced a
      DNA damage response characterized by phosphorylation of ATM (ataxia
      telangiectasia mutated), checkpoint kinase (Chk) 2/Chk1, H2AX and p53. The p53
      inhibitor pifithrin-alpha inhibited 3-NBA-induced apoptosis while small effects
      were seen using pifithrin-MU, suggesting that 3-NBA-induced cell death is a
      result of transcriptional activation of p53. In conclusion, 3-NBA is a potent
      inducer of apoptosis, which seemed to be triggered by the DNA damage response.
      Furthermore, a change of the nitro-group to the second position (i.e. 2-NBA)
      dramatically changed the cellular reactivity of the compound.

PMID- 21715571
TI  - Patterns of 'leakage' in the utilisation of clinical guidelines: a systematic
      review.
AB  - BACKGROUND: Research evidence is insufficient to change physicians' behaviour. In
      1996, Pathman developed a four step model: that physicians need to be aware of,
      agree with, adopt, and adhere to guidelines. OBJECTIVE: To review evidence in
      different settings on the patterns of 'leakage' in the utilisation of clinical
      guidelines using Pathman's awareness-to-adherence model. METHODS: A systematic
      review was conducted in June 2010. Primary studies were included if they reported
      on rates of awareness and agreement and adoption and/or adherence. RESULTS: 11
      primary studies were identified, reporting on 29 recommendations. Descriptive
      analyses of patterns and causes of leakage were tabulated and graphed. Leakage
      was progressive across all four steps. Median adherence from all recommendations
      was 34%, suggesting that potential benefits for patients from health research may
      be lost. There was considerable variation across different types of guidelines.
      Recommendations for drug interventions, vaccination and health promotion
      activities showed high rates of awareness. Leakage was most pronounced between
      adoption and adherence for drug recommendations and between awareness and
      agreement for medical management recommendations. Barriers were reported
      differentially for all steps of the model. CONCLUSION: Leakage from research
      publication to guideline utilisation occurs in a wide variety of clinical
      settings and at all steps of the awareness-to-adherence pathway. This review
      confirms that clinical guidelines are insufficient to implement research and
      suggests there may be different factors influencing clinicians at each step of
      this pathway. Recommendations to improve guideline adherence need to be tailored
      to each step.

PMID- 21715572
TI  - Effect of losartan on proteinuria and urinary angiotensinogen excretion in non
      diabetic patients with chronic kidney disease.
AB  - PURPOSE: Activation of the rennin-angiotensin system (RAS) is thought to
      contribute to hypertension and proteinuria, and eventually to the progression of
      chronic kidney disease (CKD). Recent evidence suggests that urinary
      angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This
      study was performed to determine the effect of losartan on proteinuria and UAGT
      excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria.
      STUDY DESIGN: Thirty-two patients with non-nephrotic-range proteinuria (0.045
      0.23 g/mmol creatinine) and normal renal function between April 2005 and April
      2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in
      the losartan group received losartan 50 mg/day, and the doses were titrated up to
      100 mg/day after 6 weeks. Serum and urinary angiotensinogen concentrations were
      measured by sandwich ELISA. The primary end point was the percentage change in
      proteinuria. The secondary end points were changes in estimated glomerular
      filtration rate and UAGT excretion. The follow-up period was 24 months. RESULTS:
      Baseline characteristics in the two groups were similar. After 24 months,
      losartan had reduced urinary protein excretion by 43% (from mean+/-SD 0.13+/-0.04
      to 0.073+/-0.03 g/mmol, p<0.0001), but proteinuria had not changed in the control
      group. The percentage change in mean arterial pressure did not differ between the
      groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58+/
      0.47 to 1.00+/-0.52, p=0.001). Estimated glomerular filtration rate decreased
      significantly only in the control group. CONCLUSION: Losartan significantly
      decreased proteinuria and UAGT excretion, and preserved renal function in non
      diabetic patients with CKD.

PMID- 21715573
TI  - Formaldehyde substitute fixatives: effects on nucleic acid preservation.
AB  - AIMS: In surgical pathology, formalin-fixed paraffin-embedded tissues are
      increasingly being used as a source of DNA and RNA for molecular assays in
      addition to histopathological evaluation. However, the commonly used formalin
      fixative is carcinogenic, and its crosslinking impairs DNA and RNA quality.
      METHODS: The suitability of three new presumably less toxic, crosslinking (F
      Solv) and non-crosslinking (FineFIX, RCL2) alcohol-based fixatives was tested for
      routine molecular pathology in comparison with neutral buffered formalin (NBF) as
      gold standard. Size ladder PCR, epidermal growth factor receptor sequence
      analysis, microsatellite instability (MSI), chromogenic (CISH), fluorescence in
      situ hybridisation (FISH) and qPCR were performed. RESULTS: The alcohol-based non
      crosslinking fixatives (FineFIX and RCL2) resulted in a higher DNA yield and
      quality compared with crosslinking fixatives (NBF and F-Solv). Size ladder PCR
      resulted in a shorter amplicon size (300 bp) for both crosslinking fixatives
      compared with the non-crosslinking fixatives (400 bp). All four fixatives were
      directly applicable for MSI and epidermal growth factor receptor sequence
      analysis. All fixatives except F-Solv showed clear signals in CISH and FISH. RNA
      yield and quality were superior after non-crosslinking fixation. qPCR resulted in
      lower Ct values for RCL2 and FineFIX. CONCLUSION: The alcohol-based non
      crosslinking fixatives performed better than crosslinking fixatives with regard
      to DNA and RNA yield, quality and applicability in molecular diagnostics. Given
      the higher yield, less starting material may be necessary, thereby increasing the
      applicability of biopsies for molecular studies.

PMID- 21715574
TI  - The attitudes of patients to their own autopsy: a misconception.

PMID- 21715575
TI  - Immunogenicity and safety of the influenza A/H1N1 2009 inactivated split-virus
      vaccine in young and older adults: MF59-adjuvanted vaccine versus nonadjuvanted
      vaccine.
AB  - Since initial reports in April 2009, the pandemic influenza A (H1N1) virus has
      spread globally. Influenza vaccines are the primary method for the control of
      influenza and its complications. We conducted a multicenter clinical trial to
      evaluate the immunogenicity and safety of H1N1 vaccine (Green Cross Co.) in young
      adults (18 to 64 years) and the elderly (>= 65 years) using a two-dose regimen,
      with the doses administered 21 days apart. Three different regimens of
      hemagglutinin antigen were comparatively analyzed: 3.75 MUg (MF59 adjuvanted)
      versus 7.5 MUg (MF59 adjuvanted) versus 15 MUg (nonadjuvanted) in young adults
      and 3.75 MUg (MF59 adjuvanted) versus 7.5 MUg (MF59 adjuvanted) in the elderly.
      In young adults, all three vaccine regimens met the European Agency for the
      Evaluation of Medicinal Products (EMA) criteria after the first dose. In the
      elderly, on day 21 after the first dose, the rates of seroprotection and
      seroconversion were significantly higher for the 7.5-MUg dose of MF59 adjuvanted
      vaccine than for the 3.75-MUg dose (58.0% versus 44.3% [P = 0.03] and 53.7%
      versus 37.2% [P < 0.01], respectively). After the second dose, the geometric mean
      titer (GMT) increment was blunted with a 15-MUg dose of nonadjuvanted vaccine,
      whereas the GMT increased about 2-fold with MF59 adjuvanted vaccines. In
      conclusion, a single 7.5-MUg dose of MF59 adjuvanted vaccine would have a
      practical advantage over a two-dose, 3.75-MUg, MF59 adjuvanted vaccine priming
      schedule. Following a two-dose priming schedule, the increase in hemagglutinin
      inhibition titers was higher with MF59 adjuvanted vaccine than with nonadjuvanted
      vaccine.

PMID- 21715576
TI  - A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium
      falciparum.
AB  - Plasmodium falciparum is transmitted to a new host after completing its sexual
      cycle within a mosquito. Developing vaccines against the parasite sexual stages
      is a critical component in the fight against malaria. We are targeting multiple
      proteins of P. falciparum which are found only on the surfaces of the sexual
      forms of the parasite and where antibodies against these proteins have been shown
      to block the progression of the parasite's life cycle in the mosquito and thus
      block transmission to the next human host. We have successfully produced a region
      of the Pfs230 antigen in our plant-based transient-expression system and
      evaluated this vaccine candidate in an animal model. This plant-produced protein,
      230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is
      100% soluble. Administration of 230CMB with >90% purity induces strong immune
      responses in rabbits with high titers of transmission-blocking antibodies,
      resulting in a greater than 99% reduction in oocyst counts in the presence of
      complement, as determined by a standard membrane feeding assay. Our data provide
      a clear perspective on the clinical development of a Pfs230-based transmission
      blocking malaria vaccine.

PMID- 21715577
TI  - Immunogenicity of inactivated polio vaccine with concurrent antiviral V-073
      administration in mice.
AB  - Immunization of mice with inactivated polio vaccine (IPV) with concurrent dosing
      of poliovirus antiviral V-073 showed no detrimental impact on the elicitation of
      serum-neutralizing antibodies. A strategy involving coadministration of antiviral
      V-073 and IPV can be considered for the management of poliovirus incidents.

PMID- 21715578
TI  - Immunochromatographic test with recombinant Em18 antigen for the follow-up study
      of alveolar echinococcosis.
AB  - The performance of a rapid and simple immunochromatographic test (ICT) with
      recombinant Em18 (rEm18) antigen for serological follow-up of Echinococcus
      multilocularis infection was evaluated by comparison with that of an enzyme
      linked immunosorbent assay (ELISA) with rEm18, using serum samples from patients
      who underwent surgery and/or received antiparasitic chemotherapy. The degree of
      Em18-band intensity on the ICT correlated highly with the absorbance value
      obtained by the ELISA. The kinetics of antibody levels obtained by the ICT
      paralleled those of the ELISA. These data suggest that the ICT has high potential
      as an easy-to-handle, fast, and reliable follow-up tool to monitor the status of
      alveolar echinococcosis in different stages.

PMID- 21715579
TI  - N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient
      to induce complement-dependent malaria transmission-blocking activity.
AB  - The aim of a malaria transmission-blocking vaccine is to block the development of
      malaria parasites in the mosquito and thus prevent subsequent infection of the
      human host. Previous studies have demonstrated that the gametocyte/gamete surface
      protein Pfs230 can induce transmission-blocking immunity and have evaluated
      Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In
      this study, we used the wheat germ cell-free expression system to produce N
      terminal fragments of Pfs230 and evaluated the transmission-blocking activity of
      antisera raised against the recombinant Pfs230 protein. The rabbit antisera
      reacted to the surface of cultured gametocytes and gametes of the Plasmodium
      falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by
      Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles
      stefensi mosquitoes in the presence of complement in a standard membrane feeding
      assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is
      sufficient to induce complement-dependent transmission-blocking activity against
      P. falciparum.

PMID- 21715580
TI  - Development of an automated, high-throughput bactericidal assay that measures
      cellular respiration as a survival readout for Neisseria meningitidis.
AB  - Complement-mediated bactericidal activity has long been regarded as the
      serological correlate of protective immunity against Neisseria meningitidis. This
      was affirmed in 2005 at a WHO-sponsored meningococcal serology standardization
      workshop. The assay currently employed by most laboratories involves determining
      surviving bacterial colony counts on agar as a readout which is labor-intensive,
      time-consuming, and not amendable to rapid data analysis for clinical trials.
      Consequently, there is an acute need to develop a sensitive, high-throughput
      bactericidal assay to enable a rapid and robust assessment of the effectiveness
      of vaccine candidates. To this end, we have developed an automated, kinetic assay
      based on the fluorescent respiration product of resazurin which reduces assay
      volume, shortens assay time, and facilitates automation of data analysis. We
      demonstrate proof of concept for applicability of this high-throughput system
      with multiple meningococcal strains and utilizing different lots of human
      complement. The assay is robust and highly reproducible. Titers obtained by the
      fluorescence readout method are strongly correlated with the data obtained using
      the conventional, agar plate-based assay. These results demonstrate that the
      detection of bacteria that have survived the bactericidal reaction by measuring
      metabolic activity using a fluorescent dye as an alternative readout is a
      promising approach for the development of a high-throughput bactericidal assay.

PMID- 21715581
TI  - Effect of chemotherapy on whole-blood cytokine responses to Mycobacterium
      tuberculosis antigens in a small cohort of patients with pulmonary tuberculosis.
AB  - The development of genomic and proteomic tools has enabled studies that begin to
      characterize the molecular targets of an effective host immune response to
      Mycobacterium tuberculosis, including understanding the specific immune responses
      associated with tuberculosis (TB) disease progression, disease resolution, and
      the development of latency. One application of such tools is the development of
      diagnostic reagents and assays useful as a test of cure. Such a test could be of
      considerable importance for the evaluation of new therapeutics. We and others
      have previously described immunodominant proteins of M. tuberculosis, including
      both vaccine and diagnostic candidates. In the present study, we describe the
      changes in immune responses to a panel of 71 M. tuberculosis antigens in six
      patients during the course of therapy. The levels of six cytokines were measured
      in 24-h whole-blood assays with these antigens, revealing that gamma interferon
      (IFN-gamma), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were
      differentially regulated in response to a subset of antigens. Therefore,
      measuring the production of these three cytokines in response to a panel of
      carefully selected M. tuberculosis proteins during the course of TB therapy might
      be a promising path toward the development of a test of cure and warrants further
      validation in larger cohorts of pulmonary TB patients.

PMID- 21715582
TI  - Does immunotherapy protect equines from reinfection by the oomycete Pythium
      insidiosum?
AB  - A cutaneous Pythium insidiosum reinfection was diagnosed in an equine in Brazil.
      Lesions with focal presentation appeared 2 years apart. The first infection and
      even immunotherapy were not likely to develop enough immune response to prevent
      reinfection. The use of adjuvants should be considered in the immunotherapy of
      pythiosis.

PMID- 21715583
TI  - Prognostic value of baseline plasma amino-terminal pro-brain natriuretic peptide
      and its interactions with irbesartan treatment effects in patients with heart
      failure and preserved ejection fraction: findings from the I-PRESERVE trial.
AB  - BACKGROUND: Plasma concentrations of natriuretic peptides (NPs) are associated
      with morbidity and mortality in patients with systolic heart failure (HF).
      However, the role of NP as a prognostic marker in patients with HF and preserved
      ejection fraction (HFpEF) has not been studied in a large cohort of well
      characterized patients. Moreover, it is unclear whether treatments have a
      differential effect on morbidity and mortality across the spectrum of NP levels.
      METHODS AND RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP) was
      measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart
      Failure with Preserved Ejection Fraction Trial). In a multivariable Cox
      regression model, NT-proBNP above the median of 339 pg/mL was independently
      associated with an increased risk of the primary end point of all-cause mortality
      and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR],
      1.79; 95% CI, 1.56 to 2.10; P<0.001); all-cause mortality (adjusted HR, 2.04; 95%
      CI, 1.68 to 2.47; P<0.001); and a composite of HF events, including death due to
      worsening HF or sudden death or hospitalization due to worsening HF (adjusted HR,
      1.77; 95% CI, 1.43 to 2.20; P<0.001). There were significant interactions between
      the effect of irbesartan and median split of baseline NT-proBNP for the primary
      outcome (P=0.005), all-cause mortality (P=0.05), and the HF composite outcome
      (P<0.001). Use of irbesartan was associated with improved outcomes in patients
      with NT-proBNP below, but not above, the median. After adjusting for 20 baseline
      covariates, irbesartan still had a beneficial effect on the primary outcome (HR,
      0.74; 95% CI, 0.60 to 90; P=0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56
      to 0.99; P=0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80;
      P=0.001) in patients with NT-proBNP below the median. CONCLUSIONS: The unexpected
      benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis
      may indicate effects on early, but not later, high-risk stages of the disease.
      These findings question the strategy of using elevated plasma concentrations of
      NP as a patient selection criterion in HFpEF trials. More studies are needed to
      support or contest this practice. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00095238.

PMID- 21715584
TI  - Molecular characterization of a catalase-negative Staphylococcus aureus subsp.
      aureus Strain collected from a patient with mitral valve endocarditis and
      pericarditis revealed a novel nonsense mutation in the katA gene.
AB  - We report a case of endocarditis and pericarditis caused by catalase-negative
      Staphylococcus aureus. Molecular characterization revealed a novel nonsense
      mutation in the katA gene, leading to a loss of 238 amino acids (47% of the wild
      type catalase protein), including the heme-binding site, NADPH-binding region,
      and Tyr-337, essential for catalysis.

PMID- 21715585
TI  - Diagnostic issues, clinical characteristics, and outcomes for patients with
      fungemia.
AB  - This study investigated microbiological, clinical, and management issues and
      outcomes for Danish fungemia patients. Isolates and clinical information were
      collected at six centers. A total of 334 isolates, 316 episodes, and 305 patients
      were included, corresponding to 2/3 of the national episodes. Blood culture
      positivity varied by system, species, and procedure. Thus, cases with concomitant
      bacteremia were reported less commonly by BacT/Alert than by the Bactec system
      (9% [11/124 cases] versus 28% [53/192 cases]; P < 0.0001), and cultures with
      Candida glabrata or those drawn via arterial lines needed longer incubation.
      Species distribution varied by age, prior antifungal treatment (57% occurrence of
      C. glabrata, Saccharomyces cerevisiae, or C. krusei in patients with prior
      antifungal treatment versus 28% occurrence in those without it; P = 0.007), and
      clinical specialty (61% occurrence of C. glabrata or C. krusei in hematology
      wards versus 27% occurrence in other wards; P = 0.002). Colonization samples were
      not predictive for the invasive species in 11/100 cases. Fifty-six percent of the
      patients had undergone surgery, 51% were intensive care unit (ICU) patients, and
      33% had malignant disease. Mortality increased by age (P = 0.009) and varied by
      species (36% for C. krusei, 25% for C. parapsilosis, and 14% for other Candida
      species), severity of underlying disease (47% for ICU patients versus 24% for
      others; P = 0.0001), and choice but not timing of initial therapy (12% versus 48%
      for patients with C. glabrata infection receiving caspofungin versus fluconazole;
      P = 0.023). The initial antifungal agent was deemed suboptimal upon species
      identification in 15% of the cases, which would have been 6.5% if current
      guidelines had been followed. A large proportion of Danish fungemia patients were
      severely ill and received suboptimal initial antifungal treatment. Optimization
      of diagnosis and therapy is possible.

PMID- 21715586
TI  - First three reported cases of nosocomial fungemia caused by Candida auris.
AB  - Candida auris is a newly described species whose clinical significance is not
      clear. Here, we describe the first three cases of nosocomial fungemia caused by
      C. auris, which confirms that it is a causative agent of bloodstream infections.
      All three patients presented persistent fungemia for 10 to 31 days. The isolates
      obtained from the three patients were misidentified as Candida haemulonii and
      Rhodotorula glutinis by the Vitek 2 and the API 20C systems, respectively. C.
      auris was confirmed by sequence analysis of the internal transcribed spacer
      region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. The MIC
      ranges of amphotericin B (AMB), fluconazole (FLU), itraconazole, and voriconazole
      were 0.5 to 1, 2 to 128, 0.125 to 2, and 0.06 to 1 MUg/ml, respectively. All
      isolates were susceptible to caspofungin (MIC = 0.06 MUg/ml) and micafungin (MIC
      = 0.03 MUg/ml). One patient developed breakthrough fungemia while receiving FLU
      therapy, and two patients who received FLU therapy followed by AMB showed
      therapeutic failure and fatal outcomes. Our cases show that C. auris fungemia can
      be persistent, despite FLU or AMB therapy, which emphasizes the importance of
      accurately identifying this species.

PMID- 21715587
TI  - Diagnosis of mediterranean visceral leishmaniasis by detection of leishmania
      antibodies and leishmania DNA in oral fluid samples collected using an Oracol
      device.
AB  - Current methods for diagnosis of visceral leishmaniasis (VL) require invasive
      sampling procedures such as visceral aspiration and/or blood drawing. The use of
      diagnostic tests using oral fluid, which is easier to collect, would be more
      simple and practical for VL diagnosis, especially under field conditions. Oral
      fluids from 37 VL patients and 40 healthy controls were collected using Oracol
      devices. Blood samples and oral fluid specimens from both groups were analyzed by
      recombinant protein K39 (rK39) enzyme-linked immunosorbent assay and quantitative
      real-time PCR. Detection of antibodies in the oral fluid had a sensitivity of
      100% and a specificity of 97.5%. Antibody levels measured in serum and oral fluid
      showed a significant positive correlation (rho = 0.655 and P = 0.01). Detection
      of Leishmania DNA in oral fluid had a sensitivity of 94.6% and a specificity of
      90%. The median parasite load estimated in blood was 133 parasites/ml
      (interquartile range [IR], 10 to 1,048), whereas that in oral fluid specimens was
      3 parasites/ml (IR, 0.41 to 92). However, there was no significant linear
      relationship between parasite loads assessed in the two biological samples (rho =
      0.31 and P = 0.06). VL diagnosis based on specific antibody detection and
      Leishmania DNA identification using oral fluid samples was equivalent in accuracy
      to that using blood and therefore is promising for clinical use.

PMID- 21715588
TI  - Mycobacterium haemophilum and Histoplasma capsulatum coinfection in a renal
      transplant patient.
AB  - We report the case of a 22-year-old man who presented with a Mycobacterium
      haemophilum and Histoplasma capsulatum coinfection occurring 21 years after a
      living-donor-related renal transplant.

PMID- 21715589
TI  - Evaluation of high-throughput sequencing for identifying known and unknown
      viruses in biological samples.
AB  - High-throughput sequencing furnishes a large number of short sequence reads from
      uncloned DNA and has rapidly become a major tool for identifying viruses in
      biological samples, and in particular when the target sequence is undefined. In
      this study, we assessed the analytical sensitivity of a pipeline for detection of
      viruses in biological samples based on either the Roche-454 genome sequencer or
      Illumina genome analyzer platforms. We sequenced biological samples artificially
      spiked with a wide range of viruses with genomes composed of single or double
      stranded DNA or RNA, including linear or circular single-stranded DNA. Viruses
      were added at a very low concentration most often corresponding to 3 or 0.8 times
      the validated level of detection of quantitative reverse transcriptase PCRs (RT
      PCRs). For the viruses represented, or resembling those represented, in public
      nucleotide sequence databases, we show that the higher output of Illumina is
      associated with a much greater sensitivity, approaching that of optimized
      quantitative (RT-)PCRs. In this blind study, identification of viruses was
      achieved without incorrect identification. Nevertheless, at these low
      concentrations, the number of reads generated by the Illumina platform was too
      small to facilitate assembly of contigs without the use of a reference sequence,
      thus precluding detection of unknown viruses. When the virus load was
      sufficiently high, de novo assembly permitted the generation of long contigs
      corresponding to nearly full-length genomes and thus should facilitate the
      identification of novel viruses.

PMID- 21715590
TI  - Allele-specific real-time PCR system for detection of subpopulations of genotype
      1a and 1b hepatitis C NS5B Y448H mutant viruses in clinical samples.
AB  - The Y448H mutation in NS5B has been selected by GS-9190 as well as several
      benzothiadiazine hepatitis C virus (HCV) polymerase inhibitors in vitro and in
      vivo. However, the level and the evolution kinetics of this resistance mutation
      prior to and during treatment are poorly understood. In this study, we developed
      an allele-specific real-time PCR (AS-PCR) assay capable of detecting Y448H when
      it was present at a level down to 0.5% within an HCV population of genotype 1a or
      1b. No Y448H mutation was detected above the assay cutoff of 0.5% in genotype 1b
      infected Con-1 replicons prior to in vitro treatment. However, the proportion of
      replicons with the Y448H mutation rapidly increased in a dose-dependent manner
      upon treatment with GS-9190. After 3 days of treatment, 1.2%, 6.8%, and >50% of
      the replicon population expressed Y448H with the use of GS-9190 at 1, 10, and 20
      times its 50% effective concentration, respectively. In addition, plasma from 65
      treatment-naive HCV-infected patients (42 and 23 with genotype 1a and 1b,
      respectively) was tested for the presence of Y448H by AS-PCR and population
      sequencing. As expected, all patient samples were wild type at NS5B Y448 by
      population sequencing. AS-PCR results were obtained for 62/65 samples tested,
      with low levels of Y448H ranging from 0.5% to 3.0% detected in 5/62 (8%)
      treatment-naive patient samples. These findings suggest the need for combination
      therapy with HCV-specific inhibitors to avoid viral rebound of preexisting mutant
      HCV.

PMID- 21715591
TI  - Legionella micdadei, a new cause of prosthetic joint infection.
AB  - Extrapulmonary infections caused by Legionella spp. other than Legionella
      pneumophila are rare. We report what is, to our knowledge, the first description
      of a prosthetic joint infection due to Legionella spp. Systematic testing of
      samples with suspected prosthetic infection by molecular biology techniques was
      essential. Legionella micdadei should be added to the list of microorganisms
      causing prosthetic joint infection.

PMID- 21715592
TI  - Evaluation of commercial universal rRNA gene PCR plus sequencing tests for
      identification of bacteria and fungi associated with infectious endocarditis.
AB  - Two new commercially available universal rRNA gene PCR plus sequencing tests,
      SepsiTest and universal microbe detection (UMD; Molzym, Bremen, Germany), were
      evaluated using blood specimens and heart valves from 30 patients with suspected
      infectious endocarditis (IE). The sensitivity of PCR (85%) was nearly twice as
      high as that of culture (45%), which in 10/20 IE cases presumably stayed negative
      as a consequence of growth inhibition of the pathogens by antibiotics. Further,
      PCR provided the basis for reclassification of 5/10 non-IE cases into IE cases.
      Culture-negative infections were identified by PCR, including single infections
      due to streptococci and Gram-negative bacteria (Escherichia coli, Haemophilus
      parainfluenzae) and mixed infections involving two Gram-positive bacteria or
      Candida spp. with Gram-positive bacteria. The new commercial tests proved to be
      of value for the rapid diagnosis of IE, particularly in cases of culture-negative
      infections. Issues regarding the feasibility of these tests for routine use are
      discussed.

PMID- 21715593
TI  - Performance of the LightCycler SeptiFast test Mgrade in detecting microbial
      pathogens in purulent fluids.
AB  - The performance of the LightCycler SeptiFast (SF) assay was compared to that of
      culture methods in the detection of microorganisms in 43 purulent fluids from
      patients with pyogenic infections. The SF assay was more sensitive than the
      culture methods (86% versus 61%, respectively), irrespective of whether the
      infections were mono- or polymicrobial.

PMID- 21715594
TI  - The vaccinia virus A56 protein: a multifunctional transmembrane glycoprotein that
      anchors two secreted viral proteins.
AB  - The vaccinia virus A56 protein was one of the earliest-described poxvirus
      proteins with an identifiable activity. While originally characterized as a
      haemagglutinin protein, A56 has other functions as well. The A56 protein is
      capable of binding two viral proteins, a serine protease inhibitor (K2) and the
      vaccinia virus complement control protein (VCP), and anchoring them to the
      surface of infected cells. This is important; while both proteins have
      biologically relevant functions at the cell surface, neither one can locate there
      on its own. The A56-K2 complex reduces the amount of virus superinfecting an
      infected cell and also prevents the formation of syncytia by infected cells; the
      A56-VCP complex can protect infected cells from complement attack. Deletion of
      the A56R gene results in varying effects on vaccinia virus virulence. In
      addition, since the gene encoding the A56 protein is non-essential, it can be
      used as an insertion point for foreign genes and has been deleted in some viruses
      that are in clinical development as oncolytic agents.

PMID- 21715595
TI  - Interspecies transmission of the canine influenza H3N2 virus to domestic cats in
      South Korea, 2010.
AB  - In the past 4 years, incidences of endemic or epidemic respiratory diseases
      associated with canine influenza H3N2 virus in Asian dogs have been reported in
      countries such as South Korea and China. Canine species were considered to be the
      new natural hosts for this virus. However, at the beginning of 2010, influenza
      like respiratory signs, such as dyspnoea, were also observed among cats as well
      as in dogs in an animal shelter located in Seoul, South Korea. The affected cats
      showed 100 % morbidity and 40 % mortality. We were able to isolate a virus from a
      lung specimen of a dead cat, which had suffered from the respiratory disease, in
      embryonated-chicken eggs. The eight viral genes isolated were almost identical to
      those of the canine influenza H3N2 virus, suggesting interspecies transmission of
      canine influenza H3N2 virus to the cat. Moreover, three domestic cats infected
      with intranasal canine/Korea/GCVP01/07 (H3N2) all showed elevated rectal
      temperatures, nasal virus shedding and severe pulmonary lesions, such as
      suppurative bronchopneumonia. Our study shows, for the first time, that cats are
      susceptible to canine influenza H3N2 infection, suggesting that cats may play an
      intermediate host role in transmitting the H3N2 virus among feline and canine
      species, which could lead to the endemic establishment of the virus in companion
      animals. Such a scenario raises a public health concern, as the possibility of
      the emergence of new recombinant feline or canine influenza viruses in companion
      animals with the potential to act as a zoonotic infection cannot be excluded.

PMID- 21715596
TI  - Expression profile and subcellular localization of Torque teno sus virus
      proteins.
AB  - In the present study, the expression, generation and subcellular localization of
      Torque teno sus virus (TTSuV) proteins were characterized into two genetically
      distinct TTSuV species (TTSuV1 and TTSuV2). Following transfection of three
      TTSuV1 and TTSuV2 full-length ORF (ORF1, ORF2 and ORF3) expression constructs
      into porcine kidney cells, alternative splice variants encoding new TTSuV protein
      isoforms were identified for the first time. Proteins encoded from ORF1 and ORF3
      were localized in the nucleoli of porcine kidney cells and that of ORF2 in the
      cytoplasm and nucleus excluding the nucleoli. The subcellular localization of the
      different protein isoforms was not only similar between distinct TTSuV species
      but also to the ones described in human Torque teno virus (TTV). Results of the
      present in vitro study were not based on full-length viral clones but suggested
      that alternative splicing strategy to generate TTSuV protein isoforms probably
      occurs in vivo. Obtained data provide new information on molecular biology of
      TTSuV and anelloviruses, which until now has been solely based on results
      obtained from human TTV.

PMID- 21715597
TI  - Removal of two high-mannose N-linked glycans on gp120 renders human
      immunodeficiency virus 1 largely resistant to the carbohydrate-binding agent
      griffithsin.
AB  - High-mannose N-linked glycans recognized by carbohydrate-binding agents (CBAs)
      are potential targets for topical microbicides. To better understand the
      mechanisms by which CBAs inhibit human immunodeficiency virus (HIV)-1 infection
      at the molecular level, we systematically analysed the contribution of site
      specific glycans to the anti-HIV activity of CBAs by site-directed mutagenesis.
      Our results demonstrate that a single deglycosylation at N295 or N448 in a range
      of primary and T-cell-line-adapted HIV-1 isolates resulted in marked resistance
      to griffithsin (GRFT) but maintained the sensitivity to cyanovirin (CV-N),
      Galanthus nivalis agglutinin (GNA) and a range of neutralizing antibodies. Unlike
      CV-N and GNA, the interaction between GRFT and gp120 appeared to be dependent on
      the specific trimeric 'sugar tower' including N295 and N448. This was further
      strengthened by the results of GRFT-Env binding experiments. Our study identifies
      GRFT-specific gp120 glycans and may provide information for the design of novel
      CBA antiviral strategies.

PMID- 21715598
TI  - Serological responses in humans to the smallpox vaccine LC16m8.
AB  - In response to potential bioterrorism with smallpox, members of the Japanese Self
      Defense Forces were vaccinated with vaccinia virus (VACV) strain LC16m8, an
      attenuated smallpox vaccine derived from VACV strain Lister. The serological
      response induced by LC16m8 to four virion-surface proteins and the intracellular
      mature virus (IMV) and extracellular enveloped virus (EEV) was investigated.
      LC16m8 induced antibody response against the IMV protein A27 and the EEV protein
      A56. LC16m8 also induced IMV-neutralizing antibodies, but unlike the VACV strain
      Lister, did not induce either EEV-neutralizing antibody or antibody to EEV
      protein B5, except after revaccination. Given that B5 is the only target for EEV
      neutralizing antibody and that neutralization of both IMV and EEV give optimal
      protection against orthopoxvirus challenge, these data suggest that immunity
      induced by LC16m8 might be less potent than that deriving from strain Lister.
      This potential disadvantage should be balanced against the advantage of the
      greater safety of LC16m8.

PMID- 21715599
TI  - Porphyromonas gingivalis enzymes enhance infection with human metapneumovirus in
      vitro.
AB  - Relatively recently discovered, human metapneumovirus (HMPV) is a human pathogen
      with worldwide prevalence, accounting for a substantial percentage of respiratory
      tract diseases. Concurrent viral and bacterial infections enable intricate
      mechanisms of cooperation between pathogens, which complicate the symptoms and
      outcome of the disease. Such bilateral interactions are based on the modulation
      of bacterial growth on epithelium pathologically altered during viral illness and
      the modulation of immune responses, as well as the enhancement of virus
      replication by bacterial virulence factors. This study showed that proteases
      produced by Porphyromonas gingivalis, a Gram-negative bacterium implicated in the
      development of periodontitis, named gingipains, facilitated HMPV replication in
      LLC-MK2 cells and may contribute to HMPV pathogenicity in patients with
      periodontitis. Gingipains at low nanomolar concentrations enabled HMPV
      replication and allowed virus propagation in vitro. In contrast to previously
      published data for influenza virus, however, Staphylococcus aureus proteases and
      human neutrophil elastase did not affect virus replication.

PMID- 21715600
TI  - Keratinocyte sensitization to tumour necrosis factor-induced nuclear factor kappa
      B activation by the E2 regulatory protein of human papillomaviruses.
AB  - Human papillomavirus (HPV) life cycle requires extensive manipulation of cell
      signalling to provide conditions adequate for viral replication within the
      stratified epithelia. In this regard, we show that the E2 regulatory protein of
      alpha, beta and MU-HPV genotypes enhances tumour necrosis factor (TNF)-induced
      activation of nuclear factor kappa B (NF-kappaB). This activation is mediated by
      the N-terminal domain of E2, but does not rely on its transcriptional properties.
      It is independent of the NF-kappaB regulator Tax1BP1, which nevertheless
      interacts with all the E2 proteins. E2 specifically activates NF-kappaB pathways
      induced by TNF, while interleukin-1-induced pathways are not affected. E2
      stimulates the activating K63-linked ubiquitination of TRAF5, and interacts with
      both TRAF5 and TRAF6. Our data suggest that E2 potentiates TNF-induced NF-kappaB
      signalling mediated by TRAF5 activation through direct binding. Since NF-kappaB
      controls epithelial differentiation, this activity may be involved in the
      commitment of infected keratinocytes to proliferation arrest and differentiation,
      both required for the implementation of the productive viral cycle.

PMID- 21715601
TI  - Assembly of homogeneous norovirus-like particles accomplished by amino acid
      substitution.
AB  - Infection of insect cells with recombinant baculoviruses carrying the VP1 gene
      from Chiba strain norovirus resulted in the production of 57 and 50 kDa proteins,
      and the assembly of a smaller, 23 nm form of the virus-like particles (VLPs),
      together with the normal, 38 nm form of the VLPs. The N-terminal residues of the
      57 and 50 kDa proteins were Ala4 and Thr45, respectively. When the tripeptide
      Leu43-Ala44-Thr45 was changed to Ala-Pro-Val, only 38 nm VLPs were assembled. The
      38 nm VLPs showed essentially the same pattern of carbohydrate binding as the 23
      nm VLPs, despite the significant difference in the degree of Lewis b antigen
      binding.

PMID- 21715602
TI  - Inoculation of young horses with bovine papillomavirus type 1 virions leads to
      early infection of PBMCs prior to pseudo-sarcoid formation.
AB  - Bovine papillomavirus types 1 and 2 (BPV-1 and BPV-2) are known to induce common
      equine skin tumours, termed sarcoids. Recently, it was demonstrated that
      vaccination with BPV-1 virus-like particles (VLPs) is safe and highly immunogenic
      in horses. To establish a BPV-1 challenge model for evaluation of the protective
      potential of BPV-1 VLPs, four foals were injected intradermally with infectious
      BPV-1 virions and with viral genome-based and control inocula, and monitored
      daily for tumour development. Blood was taken before inoculation and at weekly
      intervals. BPV-1-specific serum antibodies were detected by a pseudo-virion
      neutralization assay. Total nucleic acids extracted from tumours, intact skin and
      PBMCs were tested for the presence of BPV-1 DNA and mRNA using PCR and RT-PCR,
      respectively. Intralesional E5 oncoprotein expression was determined by
      immunofluorescence. Pseudo-sarcoids developed exclusively at sites inoculated
      with virions. Tumours became palpable 11-32 days after virion challenge, reached
      a size of <=20 mm in diameter and then resolved in <=6 months. No neutralizing
      anti-BPV-1 serum antibodies were detectable pre- or post-challenge. BPV-1 DNA was
      present in lesions but not in intact skin. In PBMCs, viral DNA was already
      detectable before lesions were first palpable, in concentrations correlating
      directly with tumour growth kinetics. PBMCs from two of two foals also harboured
      E5 mRNA. Immunofluorescence revealed the presence of the E5 protein in tumour
      fibroblasts, but not in the apparently normal epidermis overlying the lesions.
      Together with previous findings obtained in horses and cows, these data suggest
      that papillomavirus infection may include a viraemic phase.

PMID- 21715603
TI  - Evaluation of multiplexed cytokine and inflammation marker measurements: a
      methodologic study.
AB  - BACKGROUND: Chronic inflammation is etiologically related to several cancers. We
      evaluated the performance [ability to detect concentrations above the assay's
      lower limit of detection, coefficients of variation (CV), and intraclass
      correlation coefficients (ICC)] of 116 inflammation, immune, and metabolic
      markers across two Luminex bead-based commercial kits and three specimen types.
      METHODS: From 100 cancer-free participants in the Prostate, Lung, Colorectal, and
      Ovarian Cancer Trial, serum, heparin plasma, and EDTA plasma samples were
      utilized. We measured levels of 67 and 97 markers using Bio-Rad and Millipore
      kits, respectively. Reproducibility was assessed using 40 blinded duplicates (20
      within-batches and 20 across-batches) for each specimen type. RESULTS: A majority
      of markers were detectable in more than 25% of individuals on all specimen
      types/kits. Of the 67 Bio-Rad markers, 51, 52, and 47 markers in serum, heparin
      plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%.
      Likewise, of 97 Millipore markers, 75, 69, and 78 markers in serum, heparin
      plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%.
      When results were combined across specimen types, 45 Bio-Rad and 71 Millipore
      markers had acceptable performance (>25% detectability on all three specimen
      types and across-batch CVs <20% on at least two of three specimen types). Median
      concentrations and ICCs differed to a small extent across specimen types and to a
      large extent between Bio-Rad and Millipore. CONCLUSIONS: Inflammation and immune
      markers can be measured reliably in serum and plasma samples using multiplexed
      Luminex-based methods. IMPACT: Multiplexed assays can be utilized for
      epidemiologic investigations into the role of inflammation in cancer etiology.

PMID- 21715604
TI  - A systematic review of replication studies of prostate cancer susceptibility
      genetic variants in high-risk men originally identified from genome-wide
      association studies.
AB  - BACKGROUND: Several prostate cancer genome-wide association studies (GWAS) have
      identified risk-associated genetic variants primarily in populations of European
      descent. Less is known about the association of these variants in high-risk
      populations, including men of African descent and men with a family history of
      prostate cancer. This article provides a detailed review of published studies of
      prostate cancer-associated genetic variants originally identified in GWAS and
      replicated in high-risk populations. METHODS: Articles replicating GWAS findings
      (National Human Genome Research Institute GWAS database) were identified by
      searching PubMed and relevant data were extracted. RESULTS: Eleven replication
      studies were eligible for inclusion in this review. Of more than 30 single
      nucleotide polymorphisms (SNP) identified in prostate cancer GWAS, 19 SNPs (63%)
      were replicated in men of African descent and 10 SNPs (33%) were replicated in
      men with familial and/or hereditary prostate cancer (FPC/HPC). The majority of
      SNPs were located at the 8q24 region with modest effect sizes (OR 1.11-2.63 in
      African American men and OR 1.3-2.51 in men with FPC). All replicated SNPs at
      8q24 among men of African descent were within or near regions 2 and 3.
      CONCLUSIONS: This systematic review revealed several GWAS markers with replicated
      associations with prostate cancer in men of African descent and men with FPC/HPC.
      The 8q24 region continues to be the most implicated in prostate cancer risk.
      These replication data support ongoing study of clinical utility and potential
      function of these prostate cancer-associated variants in high-risk men. IMPACT:
      The replicated SNPs presented in this review hold promise for personalizing risk
      assessment for prostate cancer for high-risk men upon further study.

PMID- 21715605
TI  - Nonsteroidal anti-inflammatory drug and acetaminophen use and risk of adult
      myeloid leukemia.
AB  - BACKGROUND: Little is known about the causes of adult leukemia. A few small
      studies have reported a reduced risk associated with regular use of nonsteroidal
      anti-inflammatory drugs (NSAID). METHODS: In a population-based case-control
      study, we evaluated analgesic use among 670 newly diagnosed myeloid leukemia
      cases [including 420 acute myeloid leukemias (AML) and 186 chronic myeloid
      leukemias (CML)] and 701 controls aged 20 to 79 years. Prior use of aspirin,
      ibuprofen, acetaminophen, other NSAIDs, and COX-2 inhibitors was assessed and
      included frequency, duration, and quantity. ORs and 95% CIs were calculated using
      unconditional logistic regression adjusting for potential confounders. RESULTS:
      Regular/extra strength aspirin use was inversely associated with myeloid leukemia
      in women (OR = 0.59, 95% CI = 0.37-0.93) but not in men (OR = 0.85, 95% CI = 0.58
      1.24). In contrast, acetaminophen use was associated with an increased risk of
      myeloid leukemia in women only (OR = 1.60, 95% CI = 1.04-2.47). These
      relationships were stronger with increasing dose and duration. When stratified by
      leukemia type, aspirin use was inversely associated with AML and CML in women. No
      significant overall associations were found with ibuprofen or COX-2 inhibitors
      for either sex; however, a decreased risk was observed with other anti
      inflammatory analgesic use for women with AML or CML (OR = 0.47, 95% CI = 0.22
      0.99; OR = 0.31, 95% CI = 0.10-0.92, respectively). CONCLUSIONS: Our results
      provide additional support for the chemopreventive benefits of NSAIDs, at least
      in women. Because leukemia ranks fifth in person-years of life lost due to
      malignancy, further investigation is warranted. IMPACT: NSAIDs may reduce,
      whereas acetaminophen may increase, myeloid leukemia risk in women.

PMID- 21715606
TI  - Membership and boundary maintenance on an online self-harm forum.
AB  - In this article we explore how young adults became members and sustained
      membership in an online self-harm support forum, SharpTalk. We take a discursive
      approach to consider resources young people used to establish themselves, how
      others responded to their attempts, and how membership categories were developed
      and applied. Participants displayed expectations about appropriate ways of
      discussing self-harm, and about responses and advice. New posters made reference
      to other self-harm sites, provided biomedicalized narratives of their "story,"
      and asked for help in particular ways. Participants were active in shaping
      interactions on the forum, requesting input from site moderators, and challenging
      each other both on perceived infringements of posting content, and on style of
      posting pertinent to membership. On the SharpTalk site, perceived deviance in
      posting behavior, and also the giving of health care advice, were most commonly
      addressed by other young people who self-harmed, rather than by the site
      moderators. We consider implications for creating sites that enable young people
      who self-harm to become members and sustain membership, and therefore access
      support.

PMID- 21715607
TI  - An illness perception model of primary care patients' help seeking for
      depression.
AB  - Many people with depression recognize their symptoms as depression, but fail to
      seek treatment for a number of years. We aimed to explore the reasons for this.
      Thirty primary care patients who screened positive for depression participated in
      semistructured, face-to-face interviews. Transcripts were analyzed using grounded
      thematic analysis. Patients who sought depression treatment emphasized their
      understanding of depression, their belief that treatment would work, and the
      negative consequences that would ensue if they did not seek treatment. Patients
      who did not seek treatment emphasized that treatment would not be effective,
      thought that depression would not last very long, and believed that depression
      did not affect their everyday lives. Patients' illness perceptions of depression
      were represented by and organized using the framework of the Self-Regulation
      Model of Illness Behavior. This model might be useful for planning patient
      activation intervention studies to increase the uptake of depression treatment in
      primary care.

PMID- 21715608
TI  - The importance of ventral premotor cortex for body ownership processing.

PMID- 21715609
TI  - An increase in basal BDNF provokes hyperactivation of the Akt-mammalian target of
      rapamycin pathway and deregulation of local dendritic translation in a mouse
      model of Down's syndrome.
AB  - As in other diseases associated with mental retardation, dendrite morphology and
      synaptic plasticity are impaired in Down's syndrome (DS). Both these features of
      neurons are critically influenced by BDNF, which regulates local dendritic
      translation through phosphatidylinositol 3-kinase-Akt-mammalian target of
      rapamycin (mTOR) and Ras-ERK signaling cascades. Here we show that the levels of
      BDNF and phosphorylated Akt-mTOR (but not Ras-ERK) pathway proteins are augmented
      in hippocampal dendrites of Ts1Cje mice, a DS model. Consequently, the rate of
      local dendritic translation is abnormally high and the modulatory effect of
      exogenous BDNF is lost. Interestingly, rapamycin (a Food and Drug Administration
      approved drug) restores normal levels of phosphorylated Akt-mTOR proteins and
      normal rates of local translation in Ts1Cje neurons, opening new therapeutic
      perspectives for DS. The NMDAR inhibitors APV, MK-801, and memantine also restore
      the normal levels of phospho-mTOR in dendrites of Ts1Cje hippocampal neurons. We
      propose a model to explain how BDNF-mediated regulation of local translation is
      lost in the Ts1Cje hippocampus through the establishment of a glutamatergic
      positive-feedback loop. Together, these findings help elucidate the mechanisms
      underlying altered synaptic plasticity in DS.

PMID- 21715610
TI  - Human immunodeficiency virus infection of human astrocytes disrupts blood-brain
      barrier integrity by a gap junction-dependent mechanism.
AB  - HIV infection of the CNS is an early event after primary infection, resulting in
      neurological complications in a significant number of individuals despite
      antiretroviral therapy (ART). The main cells infected with HIV within the CNS are
      macrophages/microglia and a small fraction of astrocytes. The role of these few
      infected astrocytes in the pathogenesis of neuroAIDS has not been examined
      extensively. Here, we demonstrate that few HIV-infected astrocytes (4.7 +/- 2.8%
      in vitro and 8.2 +/- 3.9% in vivo) compromise blood-brain barrier (BBB)
      integrity. This BBB disruption is due to endothelial apoptosis, misguided
      astrocyte end feet, and dysregulation of lipoxygenase/cyclooxygenase, BK(Ca)
      channels, and ATP receptor activation within astrocytes. All of these alterations
      in BBB integrity induced by a few HIV-infected astrocytes were gap junction
      dependent, as blocking these channels protected the BBB from HIV-infected
      astrocyte-mediated compromise. We also demonstrated apoptosis in vivo of BBB
      cells in contact with infected astrocytes using brain tissue sections from simian
      immunodeficiency virus-infected macaques as a model of neuroAIDS, suggesting an
      important role for these few infected astrocytes in the CNS damage seen with HIV
      infection. Our findings describe a novel mechanism of bystander BBB toxicity
      mediated by low numbers of HIV-infected astrocytes and amplified by gap
      junctions. This mechanism of toxicity contributes to understanding how CNS damage
      is spread even in the current ART era and how minimal or controlled HIV infection
      still results in cognitive impairment in a large population of infected
      individuals.

PMID- 21715611
TI  - Regulation of NMDA-receptor synaptic transmission by Wnt signaling.
AB  - Wnt ligands are secreted glycoproteins controlling gene expression and
      cytoskeleton reorganization involved in embryonic development of the nervous
      system. However, their role in later stages of brain development, particularly in
      the regulation of established synaptic connections, is not known. We found that
      Wnt-5a acutely and specifically upregulates synaptic NMDAR currents in rat
      hippocampal slices, facilitating induction of long-term potentiation, a cellular
      model of learning and memory. This effect requires an increase in postsynaptic
      Ca(2+) and activation of noncanonical downstream effectors of the Wnt signaling
      pathway. In contrast, Wnt-7a, an activator of the canonical Wnt signaling
      pathway, has no effect on NMDAR-mediated synaptic transmission. Moreover,
      endogenous Wnt ligands are necessary to maintain basal NMDAR synaptic
      transmission, adjusting the threshold for synaptic potentiation. This novel role
      for Wnt ligands provides a mechanism for Wnt signaling to acutely modulate
      synaptic plasticity and brain function in later stages of development and in the
      mature organism.

PMID- 21715612
TI  - Reciprocal anatomical relationship between primary sensory and prefrontal
      cortices in the human brain.
AB  - The human brain exhibits remarkable interindividual variability in cortical
      architecture. Despite extensive evidence for the behavioral consequences of such
      anatomical variability in individual cortical regions, it is unclear whether and
      how different cortical regions covary in morphology. Using a novel approach that
      combined noninvasive cortical functional mapping with whole-brain voxel-based
      morphometric analyses, we investigated the anatomical relationship between the
      functionally mapped visual cortices and other cortical structures in healthy
      humans. We found a striking anticorrelation between the gray matter volume of
      primary visual cortex and that of anterior prefrontal cortex, independent from
      individual differences in overall brain volume. Notably, this negative
      correlation formed along anatomically separate pathways, as the dorsal and
      ventral parts of primary visual cortex showed focal anticorrelation with the
      dorsolateral and ventromedial parts of anterior prefrontal cortex, respectively.
      Moreover, a similar inverse correlation was found between primary auditory cortex
      and anterior prefrontal cortex, but no anatomical relationship was observed
      between other visual cortices and anterior prefrontal cortex. Together, these
      findings indicate that an anatomical trade-off exists between primary sensory
      cortices and anterior prefrontal cortex as a possible general principle of human
      cortical organization. This new discovery challenges the traditional view that
      the sizes of different brain areas simply scale with overall brain size and
      suggests the existence of shared genetic or developmental factors that
      contributes to the formation of anatomically and functionally distant cortical
      regions.

PMID- 21715613
TI  - Multiplicative dynamics underlie the emergence of the log-normal distribution of
      spine sizes in the neocortex in vivo.
AB  - What fundamental properties of synaptic connectivity in the neocortex stem from
      the ongoing dynamics of synaptic changes? In this study, we seek to find the
      rules shaping the stationary distribution of synaptic efficacies in the cortex.
      To address this question, we combined chronic imaging of hundreds of spines in
      the auditory cortex of mice in vivo over weeks with modeling techniques to
      quantitatively study the dynamics of spines, the morphological correlates of
      excitatory synapses in the neocortex. We found that the stationary distribution
      of spine sizes of individual neurons can be exceptionally well described by a log
      normal function. We furthermore show that spines exhibit substantial volatility
      in their sizes at timescales that range from days to months. Interestingly, the
      magnitude of changes in spine sizes is proportional to the size of the spine.
      Such multiplicative dynamics are in contrast with conventional models of synaptic
      plasticity, learning, and memory, which typically assume additive dynamics.
      Moreover, we show that the ongoing dynamics of spine sizes can be captured by a
      simple phenomenological model that operates at two timescales of days and months.
      This model converges to a log-normal distribution, bridging the gap between
      synaptic dynamics and the stationary distribution of synaptic efficacies.

PMID- 21715614
TI  - Theta-modulated head direction cells in the rat anterior thalamus.
AB  - A major tool in understanding how the brain processes information is the analysis
      of neuronal output at each hierarchical level along the pathway of signal
      propagation. Theta rhythm and head directionality are the two main signals found
      across all levels of Papez's circuit, which supports episodic memory formation.
      Here, we provide evidence that the functional interaction between both signals
      occurs at a subcortical level. We show that there is population of head direction
      cells (39%) in rat anteroventral thalamic nucleus that exhibit rhythmic spiking
      in the theta range. This class of units, termed HD-by-theta (head direction-by
      theta) cells, discharged predominantly in spike trains at theta frequency (6-12
      Hz). The highest degree of theta rhythmicity was evident when the animal was
      heading/facing in the preferred direction, expressed by the Gaussian peak of the
      directional tuning curve. The theta-rhythmic mode of spiking was closely related
      to the firing activity of local theta-bursting cells. We also found that 32% of
      anteroventral theta-bursting cells displayed a head-directional modulation of
      their spiking. This crossover between theta and head-directional signals
      indicates that anterior thalamus integrates information related to heading and
      movement, and may therefore actively modulate hippocampo-dencephalic information
      processing.

PMID- 21715615
TI  - PDGFRalpha expression distinguishes GFAP-expressing neural stem cells from PDGF
      responsive neural precursors in the adult periventricular area.
AB  - Jackson et al. (2006) have reported that adult glial fibrillary acid protein
      (GFAP)-expressing neural stem cells (NSCs) also express platelet-derived growth
      factor (PDGF) receptor-alpha (PDGFRalpha), and that their stimulation by PDGF
      induced the formation of a glioma-like mass. Here, we reexamined the relationship
      between PDGFRalpha and GFAP expression within the three-dimensional organization
      of the adult periventricular area. Using four independent PDGFRalpha antibodies,
      we found that adult mouse GFAP-expressing NSCs and PDGFRalpha-expressing cells
      represent two distinct populations of neural precursors. Examination of the adult
      periventricular area in a mouse line that expresses nuclear-localized enhanced
      green fluorescent protein under the control of the PDGFRalpha promoter confirmed
      that GFAP-expressing NSCs do not express PDGFRalpha. Furthermore, PDGF-responsive
      neural precursors were found at least one cell layer subjacent to the ependymal
      layer, and were evenly distributed across the lateral ventricular wall, which
      contrasts with the reported patchy and often ependymal localization of adult GFAP
      expressing NSCs. Adult human PDGFRalpha-expressing neural precursors were also
      found not to express GFAP. PDGF-responsive neural precursors, but not GFAP
      expressing NSCs, responded to infusions of PDGF by generating glioma-like masses.
      Our results do not support the view that GFAP-expressing NSCs are the origin of
      glioma-like masses that form after intraventricular PDGF infusion.

PMID- 21715616
TI  - Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute
      intra-axonal amyloid-beta accumulation and independently accelerates the
      development of tau abnormalities.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized
      pathologically by progressive neuronal loss, extracellular plaques containing the
      amyloid-beta (Abeta) peptides, and neurofibrillary tangles composed of
      hyperphosphorylated tau proteins. Abeta is thought to act upstream of tau,
      affecting its phosphorylation and therefore aggregation state. One of the major
      risk factors for AD is traumatic brain injury (TBI). Acute intra-axonal Abeta and
      diffuse extracellular plaques occur in ~30% of human subjects after severe TBI.
      Intra-axonal accumulations of tau but not tangle-like pathologies have also been
      found in these patients. Whether and how these acute accumulations contribute to
      subsequent AD development is not known, and the interaction between Abeta and tau
      in the setting of TBI has not been investigated. Here, we report that controlled
      cortical impact TBI in 3xTg-AD mice resulted in intra-axonal Abeta accumulations
      and increased phospho-tau immunoreactivity at 24 h and up to 7 d after TBI. Given
      these findings, we investigated the relationship between Abeta and tau
      pathologies after trauma in this model by systemic treatment of Compound E to
      inhibit gamma-secretase activity, a proteolytic process required for Abeta
      production. Compound E treatment successfully blocked posttraumatic Abeta
      accumulation in these injured mice at both time points. However, tau pathology
      was not affected. Our data support a causal role for TBI in acceleration of AD
      related pathologies and suggest that TBI may independently affect Abeta and tau
      abnormalities. Future studies will be required to assess the behavioral and long
      term neurodegenerative consequences of these pathologies.

PMID- 21715617
TI  - Postnatal development of intrinsic and synaptic properties transforms signaling
      in the layer 5 excitatory neural network of the visual cortex.
AB  - Information flow in neocortical circuits is regulated by two key parameters:
      intrinsic neuronal properties and the short-term activity-dependent plasticity of
      synaptic transmission. Using multineuronal whole-cell voltage recordings, we
      characterized the postnatal maturation of the electrophysiological properties and
      short-term plasticity of excitatory synaptic transmission between pairs of layer
      5 (L5) pyramidal neurons (n = 158) in acute slices of rat visual cortex over the
      first postnatal month. We found that the intrinsic and synaptic properties of L5
      pyramidal neurons develop in parallel. Before postnatal day 15 (P15), intrinsic
      electrophysiological properties were tuned to low-frequency operation,
      characterized by high apparent input resistance, a long membrane time constant,
      and prolonged somatic action potentials. Unitary excitatory synaptic potentials
      were of large amplitude (P11-P15; median, 514 MUV), but showed pronounced use
      dependent depression during prolonged regular and physiologically relevant
      presynaptic action potential firing patterns. In contrast, in mature animals we
      observed a developmental decline of the peak amplitude of unitary EPSPs (P25-P29;
      median, 175 MUV) paralleled by a decrease in apparent input resistance, membrane
      time constant, and somatic action potential duration. Notably, synaptic signaling
      of complex action potential firing patterns was also transformed, with P25-P29
      connections faithfully signaling action potential trains at frequencies up to 40
      Hz (1st to 50th action potential ratio, 0.91 +/- 0.12). Postnatal refinement of
      intrinsic properties and short-term plasticity therefore transforms the capacity
      of the L5 excitatory neural network of the visual cortex to generate and process
      patterns of action potential firing and contribute to network activity.

PMID- 21715618
TI  - Sensory-specific associations stored in the lateral amygdala allow for selective
      alteration of fear memories.
AB  - Consolidated long-term fear memories become labile and can be disrupted after
      being reactivated by the presentation of the unconditioned stimulus (US). Whether
      this is due to an alteration of the conditioned stimulus (CS) representation in
      the lateral amygdala (LA) is not known. Here, we show in rats that fear memory
      reactivation through presentation of the aversive US, like CS presentation,
      triggers a process which, when disrupted, results in a selective depotentiation
      of CS-evoked neural responses in the LA in correlation with a selective
      suppression of CS-elicited fear memory. Thus, an aversive US triggers the
      reconsolidation of its associated predictor representation in LA. This new
      finding suggests that sensory-specific associations are stored in the lateral
      amygdala, allowing for their selective alteration by either element of the
      association.

PMID- 21715619
TI  - Peroxisome-proliferator-activated receptor gamma coactivator 1 alpha contributes
      to dysmyelination in experimental models of Huntington's disease.
AB  - The peroxisome-proliferator-activated receptor gamma coactivator 1 alpha
      (PGC1alpha) has been implicated in the pathogenesis of several neurodegenerative
      disorders, including Huntington's disease (HD). Recent data demonstrating white
      matter abnormalities in PGC1alpha knock-out (KO) mice prompted us to examine the
      role of PGC1alpha in CNS myelination and its relevance to HD pathogenesis. We
      found deficient postnatal myelination in the striatum of PGC1alpha KO mice,
      accompanied by a decrease in myelin basic protein (MBP). In addition, brain
      cholesterol, its precursors, and the rate-limiting enzymes for cholesterol
      synthesis, HMG CoA synthase (HMGCS1) and HMG CoA reductase (HMGCR), were also
      reduced in PGC1alpha KO mice. Moreover, knockdown of PGC1alpha in
      oligodendrocytes by lentiviral shRNA led to a decrease in MBP, HMGCS1, and Hmgcr
      mRNAs. Chromatin immunoprecipitations revealed the recruitment of PGC1alpha to
      MBP promoter in mouse brain, and PGC1alpha over-expression increased MBP and
      SREBP-2 promoter activity, suggesting that PGC1alpha regulates MBP and
      cholesterol synthesis at the transcriptional level. Importantly, expression of
      mutant huntingtin (Htt) in primary oligodendrocytes resulted in decreased
      expression of PGC1alpha and its targets HmgcS1, Hmgcr, and MBP. Decreased
      expression of MBP and deficient myelination were found postnatally and in adult
      R6/2 mouse model of HD. Diffusion tensor imaging detected white matter
      abnormalities in the corpus callosum of R6/2 mice, and electron microscopy
      revealed thinner myelin sheaths and increased myelin periodicity in BACHD
      [bacterial artificial chromosome (BAC)-mediated transgenic model for Huntington's
      disease] mice expressing full-length mutant Htt. Together, these data suggest
      that PGC1alpha plays a role in postnatal myelination and that deficient PGC1alpha
      activity in oligodendrocytes may contribute to abnormal myelination in HD.

PMID- 21715620
TI  - Vicarious responses to social touch in posterior insular cortex are tuned to
      pleasant caressing speeds.
AB  - BACKGROUND: Affective touch carries strong significance for social mammals,
      including humans. Gentle, dynamic touch of a kind that occurs during social
      interactions is preferentially encoded by a distinct neural pathway involving
      tactile C (CT) afferents, a type of unmyelinated afferent nerve found exclusively
      in hairy skin. CT afferents increase firing when the skin is stroked at a
      pleasant, caress-like speed of ~3 cm/s, and their discharge frequency correlates
      with the subjective hedonic experience of the caress. In humans, the posterior
      insula is a cortical target for CT afferents. Since the potential social
      relevance of affective touch extends to the touch interactions of others, we
      postulated that information from CT afferents in posterior insular cortex
      provides a basis for encoding observed caresses. RESULTS: In two experiments, we
      exploited CT afferents' functionally unique tuning curve for stroking speed,
      demonstrating that a speed optimal for eliciting CT discharge (3 cm/s) also gives
      rise to higher BOLD responses in posterior insula than a nonoptimal speed (30
      cm/s). When participants viewed videos of others' arms being stroked at CT
      optimal versus -nonoptimal speeds, the posterior insula showed a similar response
      as to directly felt touch. Further, this region's response was specific for
      social interactions, showing no CT-related modulation for nonsocial dynamic-touch
      videos. CONCLUSIONS: These findings provide direct evidence for a functional
      relationship between CT signaling and processing in posterior insular cortex.
      Such selective tuning for CT-optimal signals in insula may allow recognition of
      the hedonic relevance of a merely observed caress.

PMID- 21715621
TI  - Sapap3 deletion anomalously activates short-term endocannabinoid-mediated
      synaptic plasticity.
AB  - Retrograde synaptic signaling by endocannabinoids (eCBs) is a widespread
      mechanism for activity-dependent inhibition of synaptic strength in the brain.
      Although prevalent, the conditions for eliciting eCB-mediated synaptic depression
      vary among brain circuits. As yet, relatively little is known about the molecular
      mechanisms underlying this variation, although the initial signaling events are
      likely dictated by postsynaptic proteins. SAP90/PSD-95-associated proteins
      (SAPAPs) are a family of postsynaptic proteins unique to excitatory synapses.
      Using Sapap3 knock-out (KO) mice, we find that, in the absence of SAPAP3,
      striatal medium spiny neuron (MSN) excitatory synapses exhibit eCB-mediated
      synaptic depression under conditions that do not normally activate this process.
      The anomalous synaptic plasticity requires type 5 metabotropic glutamate
      receptors (mGluR5s), which we find are dysregulated in Sapap3 KO MSNs. Both
      surface expression and activity of mGluR5s are increased in Sapap3 KO MSNs,
      suggesting that enhanced mGluR5 activity may drive the anomalous synaptic
      plasticity. In direct support of this possibility, we find that, in wild-type
      (WT) MSNs, pharmacological enhancement of mGluR5 by a positive allosteric
      modulator is sufficient to reproduce the increased synaptic depression seen in
      Sapap3 KO MSNs. The same pharmacologic treatment, however, fails to elicit
      further depression in KO MSNs. Under conditions that are sufficient to engage eCB
      mediated synaptic depression in WT MSNs, Sapap3 deletion does not alter the
      magnitude of the response. These results identify a role for SAPAP3 in the
      regulation of postsynaptic mGluRs and eCB-mediated synaptic plasticity. SAPAPs,
      through their effect on mGluR activity, may serve as regulatory molecules gating
      the threshold for inducing eCB-mediated synaptic plasticity.

PMID- 21715622
TI  - Functional development of large-scale sensorimotor cortical networks in the
      brain.
AB  - Large-scale neuronal networks integrating several cortical areas mediate the
      complex functions of the brain such as sensorimotor integration. Little is known
      about the functional development of these networks and the maturational processes
      by which distant networks become functionally connected. We addressed this
      question in the postnatal rat sensorimotor system. Using epicranial
      multielectrode grids that span most of the cortical surface and intracortical
      electrodes, we show that sensory evoked cortical responses continuously maturate
      throughout the first 3 weeks with the strongest developmental changes occurring
      in a very short time around postnatal day 13 (P13). Before P13, whisker
      stimulation evokes slow, initially surface-negative activity restricted mostly to
      the lateral parietal area of the contralateral hemisphere. In a narrow time
      window of ~48 h around P13, a new early, sharp surface-positive component emerges
      that coincides with subsequent propagation of activity to sensory and motor areas
      of both hemispheres. Our data show that this new component developing at the end
      of the second week corresponds principally to functional maturation of the
      supragranular cortical layers and appears to be crucial for the functional
      associations in the large-scale sensorimotor cortical network. It goes along with
      the onset of whisking behavior, as well as major synaptic and functional changes
      within the S1 cortex that are known to develop during this period.

PMID- 21715623
TI  - Differential electrophysiological coupling for positive and negative BOLD
      responses during unilateral hand movements.
AB  - The coupling between neural cellular activity and blood oxygen level-dependent
      (BOLD) signal is of critical importance to the interpretation of fMRI. Largely
      unknown, however, is the degree to which different neuronal events (i.e.,
      excitation and inhibition) maintain or disrupt the neural-hemodynamic
      relationship, especially in humans. In the present study, we compared local
      electroencephalographic (EEG) oscillations and the positive/negative BOLD
      responses of simultaneously recorded data from healthy human volunteers
      performing unilateral finger tapping at graded rates. By quantifying the single
      trial modulations of EEG using source imaging, we tested for their correlation
      with positive BOLD response (PBR) and negative BOLD response (NBR) after
      coregistering their spatial locations. PBR was found to be overlapped with and
      correlated to the decrease of alpha (8-13 Hz) and beta (13-30 Hz) band EEG in the
      contralateral sensorimotor cortex. Regional EEG modulations at the sensorimotor
      cortex further predicted a spatially distributed and interconnected network of
      motor-related cortical areas. Alternatively, no significant correlation was found
      at the ipsilateral sensorimotor cortex between the NBR and EEG despite their
      spatial overlapping. This differential electrophysiological coupling of the
      positive and negative BOLD responses suggests that the underlying neuronal events
      may not only influence the direction of the signal change but also the neural
      hemodynamic relationship.

PMID- 21715624
TI  - Visual attention modulates brain activation to angry voices.
AB  - In accordance with influential models proposing prioritized processing of threat,
      previous studies have shown automatic brain responses to angry prosody in the
      amygdala and the auditory cortex under auditory distraction conditions. However,
      it is unknown whether the automatic processing of angry prosody is also observed
      during cross-modal distraction. The current fMRI study investigated brain
      responses to angry versus neutral prosodic stimuli during visual distraction.
      During scanning, participants were exposed to angry or neutral prosodic stimuli
      while visual symbols were displayed simultaneously. By means of task
      requirements, participants either attended to the voices or to the visual
      stimuli. While the auditory task revealed pronounced activation in the auditory
      cortex and amygdala to angry versus neutral prosody, this effect was absent
      during the visual task. Thus, our results show a limitation of the automaticity
      of the activation of the amygdala and auditory cortex to angry prosody. The
      activation of these areas to threat-related voices depends on modality-specific
      attention.

PMID- 21715625
TI  - Decoding action intentions from preparatory brain activity in human parieto
      frontal networks.
AB  - How and where in the human brain high-level sensorimotor processes such as
      intentions and decisions are coded remain important yet essentially unanswered
      questions. This is in part because, to date, decoding intended actions from brain
      signals has been primarily constrained to invasive neural recordings in nonhuman
      primates. Here we demonstrate using functional MRI (fMRI) pattern recognition
      techniques that we can also decode movement intentions from human brain signals,
      specifically object-directed grasp and reach movements, moments before their
      initiation. Subjects performed an event-related delayed movement task toward a
      single centrally located object (consisting of a small cube attached atop a
      larger cube). For each trial, after visual presentation of the object, one of
      three hand movements was instructed: grasp the top cube, grasp the bottom cube,
      or reach to touch the side of the object (without preshaping the hand). We found
      that, despite an absence of fMRI signal amplitude differences between the planned
      movements, the spatial activity patterns in multiple parietal and premotor brain
      areas accurately predicted upcoming grasp and reach movements. Furthermore, the
      patterns of activity in a subset of these areas additionally predicted which of
      the two cubes were to be grasped. These findings offer new insights into the
      detailed movement information contained in human preparatory brain activity and
      advance our present understanding of sensorimotor planning processes through a
      unique description of parieto-frontal regions according to the specific types of
      hand movements they can predict.

PMID- 21715626
TI  - The c-Abl-MST1 signaling pathway mediates oxidative stress-induced neuronal cell
      death.
AB  - Oxidative stress influences cell survival and homeostasis, but the mechanisms
      underlying the biological effects of oxidative stress remain to be elucidated.
      The protein kinase MST1 (mammalian Ste20-like kinase 1) plays a major role in
      oxidative stress-induced cell death in primary mammalian neurons. However, the
      mechanisms that regulate MST1 in oxidative stress responses remain largely
      unknown. In the present study, we demonstrate that the protein kinase c-Abl
      phosphorylates MST1 at Y433, which triggers the stabilization and activation of
      MST1. Inhibition of c-Abl promotes the degradation of MST1 through C terminus of
      Hsc70-interacting protein (CHIP)-mediated ubiquitination, and thereby attenuates
      cell death. Oxidative stress induces the c-Abl-dependent tyrosine phosphorylation
      of MST1 and increases the interaction between MST1 and FOXO3 (Forkhead box O3),
      thereby activating the MST1-FOXO signaling pathway, leading to cell death in both
      primary culture neurons and rat hippocampal neurons. The identification of the c
      Abl tyrosine kinase as a novel upstream activator of MST1 suggests that the c-Abl
      MST1 signaling cascade plays an important role in cellular responses to oxidative
      stress.

PMID- 21715627
TI  - Interplay between LXR and Wnt/beta-catenin signaling in the negative regulation
      of peripheral myelin genes by oxysterols.
AB  - Oxysterols are reactive molecules generated from the oxidation of cholesterol.
      Their implication in cholesterol homeostasis and in the progression of
      neurodegenerative disorders is well known, but few data are available for their
      functions in the peripheral nervous system. Our aim was to study the influence of
      oxysterols on myelin gene expression and myelin sheath formation in peripheral
      nerves. We show by gas chromatography/mass spectrometry that Schwann cells and
      sciatic nerves contain 24(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27
      hydroxycholesterol and that they express their biosynthetic enzymes and receptors
      (liver X receptors LXRalpha and LXRbeta). We demonstrate that oxysterols inhibit
      peripheral myelin gene expression [myelin protein zero (MPZ) and peripheral
      myelin protein-22 (PMP22)] in a Schwann cell line. This downregulation is
      mediated by either LXRalpha or LXRbeta, depending on the promoter context, as
      suggested by siRNA strategy and chromatin immunoprecipitation assays in Schwann
      cells and in the sciatic nerve of LXR knock-out mice. Importantly, the knock-out
      of LXR in mice results in thinner myelin sheaths surrounding the axons.
      Oxysterols repress myelin genes via two mechanisms: by binding of LXRs to myelin
      gene promoters and by inhibiting the Wnt/beta-catenin pathway that is crucial for
      the expression of myelin genes. The Wnt signaling components (Disheveled,
      TCF/LEF, beta-catenin) are strongly repressed by oxysterols. Furthermore, the
      recruitment of beta-catenin at the levels of the MPZ and PMP22 promoters is
      decreased. Our data reveal new endogenous mechanisms for the negative regulation
      of myelin gene expression, highlight the importance of oxysterols and LXR in
      peripheral nerve myelination, and open new perspectives of treating demyelinating
      diseases with LXR agonists.

PMID- 21715628
TI  - Critical period of axoglial signaling between neuregulin-1 and brain-derived
      neurotrophic factor required for early Schwann cell survival and differentiation.
AB  - During peripheral nervous system development, successful communication between
      axons and Schwann cells is required for proper function of both myelinated and
      nonmyelinated nerve fibers. Alternatively spliced proteins belonging to the
      neuregulin1 (NRG1) gene family of growth and differentiation factors are
      essential for Schwann cell survival and peripheral nerve development. Although
      recent studies have strongly implicated membrane-bound NRG1 forms (type III) in
      the myelination at late stages, little is known about the role of soluble,
      heparin-binding forms of NRG1 (type I/II) in regulating early Schwann cell
      development in vivo. These forms are rapidly released from axons in vitro by
      Schwann-cell-secreted neurotrophic factors and, unlike membrane-bound forms, have
      a unique ability to diffuse and adhere to heparan sulfate-rich cell surfaces.
      Here, we show that axon-derived soluble NRG1 translocates from axonal to Schwann
      cell surfaces in the embryonic chick between days 5 and 7, corresponding to the
      critical period of Schwann cell survival. Downregulating endogenous type I/II
      NRG1 signaling either with a targeted NRG1 antagonist or by shRNA blocks their
      differentiation from precursors into immature Schwann cells and increases
      programmed cell death, whereas upregulating NRG1 rescues Schwann cells. Exogenous
      BDNF also promotes Schwann cell survival through promoting the local release of
      axonal NRG1. Consistently, increased Schwann cell death occurs both in trkB knock
      out mice and after knocking down axonal trkB in chick embryos, which can then be
      rescued with soluble NRG1. These findings suggest a localized, axoglial feedback
      loop through soluble NRG1 and BDNF critical for early Schwann cell survival and
      differentiation.

PMID- 21715629
TI  - Prediction of reading skill several years later depends on age and brain region:
      implications for developmental models of reading.
AB  - We investigated whether brain activity was predictive of future reading skill
      and, if so, how this brain-behavior correlation informs developmental models of
      reading. A longitudinal study followed 26 normally developing human children
      ranging in age from 9 to 15 years who were initially assessed for reading skill
      and performed a rhyming judgment task during functional magnetic resonance
      imaging. Patterns of brain activation in this task predicted changes between
      initial and a follow-up assessment of nonword reading skill administered up to 6
      years later. Brain activity in areas typically active during imaging studies of
      reading was found to predict future nonword reading ability, but the predictive
      ability of these areas depended on age. Increased activity relative to peers in
      neural circuits associated with phonological recoding (i.e., inferior frontal
      gyrus and basal ganglia) was predictive of greater gains in reading fluency in
      younger children, whereas increased activity relative to peers in orthographic
      processing circuits (i.e., fusiform gyrus) was predictive of smaller gains in
      fluency for older children. Interpreted within the context of a connectionist
      model of reading, these results suggest that younger children who are more
      sensitive to higher-order phonological word characteristics (e.g.,
      coarticulations) may make greater reading proficiency gains, whereas older
      children who focus more on whole-word orthographic representations may make
      smaller proficiency gains.

PMID- 21715630
TI  - Androgens and estrogens synergistically regulate the expression of doublecortin
      and enhance neuronal recruitment in the song system of adult female canaries.
AB  - Vocal control nuclei in songbirds display seasonal changes in volume that are
      regulated by testosterone (T) and its androgenic (5alpha-dihydrotestosterone;
      DHT) or estrogenic (17beta-estradiol; E(2)) metabolites. In male canaries, T
      regulates expression of the microtubule-associated protein doublecortin (DCX), a
      marker of neurogenesis. We examined the effect of T and its two metabolites alone
      or in combination on DCX expression in adult female canaries. Treatment with T or
      with DHT+E(2) increased HVC volume and neuron numbers as well as the total
      numbers of fusiform (migrating) and round (differentiating) DCX neurons in the
      nucleus but generally not in adjacent areas. DHT or E(2) alone did not increase
      these measures but increased the density of fusiform DCX cells per section.
      Similar results were observed in area X, although some effects did not reach
      significance, presumably because plasticity in X is mediated transsynaptically
      and follows HVC changes with some delay. There was no effect of any treatment on
      the total number of neurons in area X, and no change in DCX cell densities was
      detected in the lateral magnocellular nucleus of the anterior nidopallium, nor in
      other parts of the nidopallium. DHT and E(2) by themselves thus increase density
      of DCX cells migrating through HVC but are not sufficient in isolation to induce
      the recruitment of these newborn neurons in the nucleus. These effects are
      generally not observed in the rest of the nidopallium, implying that steroids
      only act on the attraction and recruitment of new neurons in HVC without having
      any major effects on their production at the ventricle wall.

PMID- 21715631
TI  - Is gamma-band activity in the local field potential of V1 cortex a "clock" or
      filtered noise?
AB  - Gamma-band (25-90 Hz) peaks in local field potential (LFP) power spectra are
      present throughout the cerebral cortex and have been related to perception,
      attention, memory, and disorders (e.g., schizophrenia and autism). It has been
      theorized that gamma oscillations provide a "clock" for precise temporal encoding
      and "binding" of signals about stimulus features across brain regions. For gamma
      to function as a clock, it must be autocoherent: phase and frequency conserved
      over a period of time. We computed phase and frequency trajectories of gamma-band
      bursts, using time-frequency analysis of LFPs recorded in macaque primary visual
      cortex (V1) during visual stimulation. The data were compared with simulations of
      random networks and clock signals in noise. Gamma-band bursts in LFP data were
      statistically indistinguishable from those found in filtered broadband noise.
      Therefore, V1 LFP data did not contain clock-like gamma-band signals. We consider
      possible functions for stochastic gamma-band activity, such as a synchronizing
      pulse signal.

PMID- 21715632
TI  - Why clowns taste funny: the relationship between humor and semantic ambiguity.
AB  - What makes us laugh? One crucial component of many jokes is the disambiguation of
      words with multiple meanings. In this functional MRI study of normal
      participants, the neural mechanisms that underlie our experience of getting a
      joke that depends on the resolution of semantically ambiguous words were
      explored. Jokes that contained ambiguous words were compared with sentences that
      contained ambiguous words but were not funny, as well as to matched verbal jokes
      that did not depend on semantic ambiguity. The results confirm that both the left
      inferior temporal gyrus and left inferior frontal gyrus are involved in
      processing the semantic aspects of language comprehension, while a more
      widespread network that includes both of these regions and the temporoparietal
      junction bilaterally is involved in processing humorous verbal jokes when
      compared with matched nonhumorous material. In addition, hearing jokes was
      associated with increased activity in a network of subcortical regions, including
      the amygdala, the ventral striatum, and the midbrain, that have been implicated
      in experiencing positive reward. Moreover, activity in these regions correlated
      with the subjective ratings of funniness of the presented material. These results
      allow a more precise account of how the neural and cognitive processes that are
      involved in ambiguity resolution contribute to the appreciation of jokes that
      depend on semantic ambiguity.

PMID- 21715633
TI  - Allosteric modulation of retinal GABA receptors by ascorbic acid.
AB  - Ionotropic GABA receptors (GABA(A) and GABA(C)) belong to the Cys-loop receptor
      family of ligand-gated ion channels. GABA(C) receptors are highly expressed in
      the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic
      acid, an endogenous redox agent, modulates the function of diverse proteins, and
      basal levels of ascorbic acid in the retina are very high. However, the effect of
      ascorbic acid on retinal GABA receptors has not been studied. Here we show that
      the function of GABA(C) and GABA(A) receptors is regulated by ascorbic acid.
      Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices
      revealed that GABA(C) receptor-mediated currents activated by tonic background
      levels of extracellular GABA, and GABA(C) currents elicited by local GABA puffs,
      are both significantly enhanced by ascorbic acid. In addition, a significant
      rundown of GABA puff-evoked currents was observed in the absence of ascorbic
      acid. GABA-evoked Cl(-) currents mediated by homomeric rho(1) GABA(C) receptors
      expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a
      concentration-dependent, stereo-specific, reversible, and voltage-independent
      manner. Studies involving the chemical modification of sulfhydryl groups showed
      that the two Cys-loop cysteines and histidine 141, all located in the rho(1)
      subunit extracellular domain, each play a key role in the modulation of GABA(C)
      receptors by ascorbic acid. Additionally, we show that retinal GABA(A) IPSCs and
      heterologously expressed GABA(A) receptor currents are similarly augmented by
      ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous
      agent capable of potentiating GABAergic neurotransmission in the CNS.

PMID- 21715634
TI  - A common substrate for prefrontal and hippocampal inhibition of the
      neuroendocrine stress response.
AB  - A network of interconnected limbic forebrain cell groups, including the medial
      prefrontal cortex (mPFC) and hippocampal formation (HF), is known to shape
      adaptive responses to emotionally stressful experiences, including output of the
      hypothalamo-pituitary-adrenal (HPA) axis. While disruption of limbic HPA
      inhibitory systems is implicated in stress-related psychiatric and systemic
      illnesses, progress in the field has been hampered by a lack of a systems-level
      understanding of the organization that provides for this regulation. Using rats,
      we first localized cell groups afferent to the paraventricular hypothalamic
      nucleus (PVH) (the initiator of HPA responses to stress) whose engagement
      following acute (30 min) restraint was diminished by excitotoxin lesions of the
      ventral subiculum, a component of the HF. This identified a candidate relay for
      imparting HF influences in a circumscribed portion of the anterior bed nucleus of
      the stria terminalis (aBST), which we previously identified as a GABAergic relay
      subserving mPFC inhibition of the stress axis. Anatomical tracing experiments
      then indicated that extrinsic projections from HF and mPFC converge onto regions
      of aBST that contain neurons that are both stress sensitive and PVH projecting.
      Two final experiments provided evidence that (1) HPA-inhibitory influences of
      mPFC and HF are additive and (2) aBST plays a more prominent inhibitory role than
      ventral subiculum over stress-induced HPA endpoints. These findings support the
      view that stress-inhibitory influences of mPFC and HF are exerted principally via
      convergence onto a common relay, as opposed to a serial, parallel, or more
      complex multisynaptic network.

PMID- 21715635
TI  - Presynapses in Kenyon cell dendrites in the mushroom body calyx of Drosophila.
AB  - Plastic changes at the presynaptic sites of the mushroom body (MB) principal
      neurons called Kenyon cells (KCs) are considered to represent a neuronal
      substrate underlying olfactory learning and memory. It is generally believed that
      presynaptic and postsynaptic sites of KCs are spatially segregated. In the MB
      calyx, KCs receive olfactory input from projection neurons (PNs) on their
      dendrites. Their presynaptic sites, however, are thought to be restricted to the
      axonal projections within the MB lobes. Here, we show that KCs also form
      presynapses along their calycal dendrites, by using novel transgenic tools for
      visualizing presynaptic active zones and postsynaptic densities. At these
      presynapses, vesicle release following stimulation could be observed. They reside
      at a distance from the PN input into the KC dendrites, suggesting that regions of
      presynaptic and postsynaptic differentiation are segregated along individual KC
      dendrites. KC presynapses are present in gamma-type KCs that support short- and
      long-term memory in adult flies and larvae. They can also be observed in
      alpha/beta-type KCs, which are involved in memory retrieval, but not in
      alpha'/beta'-type KCs, which are implicated in memory acquisition and
      consolidation. We hypothesize that, as in mammals, recurrent activity loops might
      operate for memory retrieval in the fly olfactory system. The newly identified KC
      derived presynapses in the calyx are, inter alia, candidate sites for the
      formation of memory traces during olfactory learning.

PMID- 21715636
TI  - Stimulus-specific adaptation in the gerbil primary auditory thalamus is the
      result of a fast frequency-specific habituation and is regulated by the
      corticofugal system.
AB  - The detection of novel and therefore potentially behavioral relevant stimuli is
      of fundamental importance for animals. In the auditory system, stimulus-specific
      adaptation (SSA) resulting in stronger responses to rare compared with frequent
      stimuli was proposed as such a novelty detection mechanism. SSA is a now well
      established phenomenon found at different levels along the mammalian auditory
      pathway. It depends on various stimulus features, such as deviant probability,
      and may be an essential mechanism underlying perception of changes in sound
      statistics. We recorded neuronal responses from the ventral part of the medial
      geniculate body (vMGB) in Mongolian gerbils to determine details of the
      adaptation process that might indicate underlying neuronal mechanisms. Neurons in
      the vMGB exhibited a median spike rate change of 15.4% attributable to a fast
      habituation to the frequently presented standard stimulus. Accordingly, the main
      habituation effect could also be induced by the repetition of a few uniform tonal
      stimuli. The degree of habituation was frequency-specific, and comparison across
      simultaneously recorded units indicated that adaptation effects were apparently
      topographically organized. At the population level, stronger habituation effects
      were on average associated with the border regions of the frequency response
      areas. Finally, the pharmacological inactivation of the auditory cortex
      demonstrated that SSA in the vMGB is mainly regulated by the corticofugal system.
      Hence, these results indicate a more general function of SSA in the processing
      and analysis of auditory information than the term novelty detection suggests.

PMID- 21715637
TI  - Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a
      display novel channel properties and contribute to acidosis-induced neuronal
      death.
AB  - Acid-sensing ion channel (ASIC) subunits associate to form homomeric or
      heteromeric proton-gated ion channels in neurons throughout the nervous system.
      The ASIC1a subunit plays an important role in establishing the kinetics of proton
      gated currents in the CNS, and activation of ASIC1a homomeric channels induces
      neuronal death after local acidosis that accompanies cerebral ischemia. The
      ASIC2b subunit is expressed in the brain in a pattern that overlaps ASIC1a, yet
      the contribution of ASIC2b has remained elusive. We find that coexpression of
      ASIC2b with ASIC1a in Xenopus oocytes results in novel proton-gated currents with
      properties distinct from ASIC1a homomeric channels. In particular, ASIC2b/1a
      heteromeric channels are inhibited by the nonselective potassium channel blockers
      tetraethylammonium and barium. In addition, steady-state desensitization is
      induced at more basic pH values, and Big Dynorphin sensitivity is enhanced in
      these unique heteromeric channels. Cultured hippocampal neurons show proton-gated
      currents consistent with ASIC2b contribution, and these currents are lacking in
      neurons from mice with an ACCN1 (ASIC2) gene disruption. Finally, we find that
      these ASIC2b/1a heteromeric channels contribute to acidosis-induced neuronal
      death. Together, our results show that ASIC2b confers unique properties to
      heteromeric channels in central neurons. Furthermore, these data indicate that
      ASIC2, like ASIC1, plays a role in acidosis-induced neuronal death and implicate
      the ASIC2b/1a subtype as a novel pharmacological target to prevent neuronal
      injury after stroke.

PMID- 21715638
TI  - BDNF-promoted increases in proximal dendrites occur via CREB-dependent
      transcriptional regulation of cypin.
AB  - Alterations in dendrite branching and morphology are present in many
      neurodegenerative diseases. These variations disrupt postsynaptic transmission
      and affect neuronal communication. Thus, it is important to understand the
      molecular mechanisms that regulate dendritogenesis and how they go awry during
      disease states. Previously, our laboratory showed that cypin, a mammalian guanine
      deaminase, increases dendrite number when overexpressed and decreases dendrite
      number when knocked down in cultured hippocampal neurons. Here, we report that
      exposure to brain-derived neurotrophic factor (BDNF), an important mediator of
      dendrite arborization, for 72 h but not for 24 h or less increases cypin mRNA and
      protein levels in rat hippocampal neurons. BDNF signals through cypin to regulate
      dendrite number, since knocking down cypin blocks the effects of BDNF.
      Furthermore, BDNF increases cypin levels via mitogen-activated protein kinase and
      transcription-dependent signaling pathways. Moreover, the cypin promoter region
      contains putative conserved cAMP response element (CRE) regions, which we found
      can be recognized and activated by CRE-binding protein (CREB). In addition,
      exposure of the neurons to BDNF increased CREB binding to the cypin promoter and,
      in line with these data, expression of a dominant negative form of CREB blocked
      BDNF-promoted increases in cypin protein levels and proximal dendrite branches.
      Together, these studies suggest that BDNF increases neuronal cypin expression by
      the activation of CREB, increasing cypin transcription leading to increased
      protein expression, thus identifying a novel pathway by which BDNF shapes the
      dendrite network.

PMID- 21715639
TI  - Mitochondrial DNA damage level determines neural stem cell differentiation fate.
AB  - The mitochondrial DNA (mtDNA) of neural stem cells (NSCs) is vulnerable to
      oxidation damage. Subtle manipulations of the cellular redox state affect mtDNA
      integrity in addition to regulating the NSC differentiation lineage, suggesting a
      molecular link between mtDNA integrity and regulation of differentiation. Here we
      show that 8-oxoguanine DNA glycosylase (OGG1) is essential for repair of mtDNA
      damage and NSC viability during mitochondrial oxidative stress. Differentiating
      neural cells from ogg1(-/-) knock-out mice spontaneously accumulate mtDNA damage
      and concomitantly shift their differentiation direction toward an astrocytic
      lineage, similar to wt NSCs subjected to mtDNA damaging insults. Antioxidant
      treatments reversed mtDNA damage accumulation and separately increased
      neurogenesis in ogg1(-/-) cells. NSCs from a transgenic ogg1(-/-) mouse
      expressing mitochondrially targeted human OGG1 were protected from mtDNA damage
      during differentiation, and displayed elevated neurogenesis. The underlying
      mechanisms for this shift in differentiation direction involve the astrogenesis
      promoting Sirt1 via an increased NAD/NADH ratio in ogg1(-/-) cells. Redox
      manipulations to alter mtDNA damage level correspondingly activated Sirt1 in both
      cell types. Our results demonstrate for the first time the interdependence
      between mtDNA integrity and NSC differentiation fate, suggesting that mtDNA
      damage is the primary signal for the elevated astrogliosis and lack of
      neurogenesis seen during repair of neuronal injury.

PMID- 21715640
TI  - The neural underpinnings of how reward associations can both guide and misguide
      attention.
AB  - It is commonly accepted that reward is an effective motivator of behavior, but
      little is known about potential costs resulting from reward associations. Here,
      we used functional magnetic resonance imaging (fMRI) to investigate the neural
      underpinnings of such reward-related performance-disrupting effects in a reward
      modulated Stroop task in humans. While reward associations in the task-relevant
      dimension (i.e., ink color) facilitated performance, behavioral detriments were
      found when the task-irrelevant dimension (i.e., word meaning) implicitly referred
      to reward-predictive ink colors. Neurally, only relevant reward associations
      invoked a typical reward-anticipation response in the nucleus accumbens (NAcc),
      which was in turn predictive of behavioral facilitation. In contrast, irrelevant
      reward associations increased activity in a medial prefrontal motor-control
      related region, namely the presupplementary motor area (pre-SMA), which likely
      reflects the preemption and inhibition of automatic response tendencies that are
      amplified by irrelevant reward-related words. This view was further supported by
      a positive relationship between pre-SMA activity and pronounced response slowing
      in trials containing reward-related as compared with reward-unrelated incongruent
      words. Importantly, the distinct neural processes related to the beneficial and
      detrimental behavioral effects of reward associations appeared to arise from
      preferential-coding mechanisms in visual-processing areas that were shared by the
      two stimulus dimensions, suggesting a transfer of reward-related saliency to the
      irrelevant dimension, but with highly differential behavioral and neural
      ramifications. More generally, the data demonstrate that even entirely irrelevant
      reward associations can influence stimulus-processing and response-selection
      pathways relatively automatically, thereby representing an important flipside of
      reward-driven performance enhancements.

PMID- 21715641
TI  - Enhanced control of attention by stimulating mesolimbic-corticopetal cholinergic
      circuitry.
AB  - Sustaining and recovering attentional performance requires interactions between
      the brain's motivation and attention systems. The first experiment demonstrated
      that in rats performing a sustained attention task (SAT), presentation of a
      distractor (dSAT) augmented performance-associated increases in cholinergic
      neurotransmission in prefrontal cortex. Because stimulation of NMDA receptors in
      the shell of the nucleus accumbens activates PFC cholinergic neurotransmission, a
      second experiment demonstrated that bilateral infusions of NMDA into the NAc
      shell, but not core, improved dSAT performance to levels observed in the absence
      of a distractor. A third experiment demonstrated that removal of prefrontal or
      posterior parietal cholinergic inputs, by intracortical infusions of the
      cholinotoxin 192 IgG-saporin, attenuated the beneficial effects of NMDA on dSAT
      performance. Mesolimbic activation of cholinergic projections to the cortex
      benefits the cognitive control of attentional performance by enhancing the
      detection of cues and the filtering of distractors.

PMID- 21715643
TI  - Should graphs of risk or rate ratios be plotted on a log scale?

PMID- 21715642
TI  - The master negative regulator REST/NRSF controls adult neurogenesis by
      restraining the neurogenic program in quiescent stem cells.
AB  - Transcriptional regulation is a critical mechanism in the birth, specification,
      and differentiation of granule neurons in the adult hippocampus. One of the first
      negative-acting transcriptional regulators implicated in vertebrate development
      is repressor element 1-silencing transcription/neuron-restrictive silencer factor
      (REST/NRSF)--thought to regulate hundreds of neuron-specific genes--yet its
      function in the adult brain remains elusive. Here we report that REST/NRSF is
      required to maintain the adult neural stem cell (NSC) pool and orchestrate stage
      specific differentiation. REST/NRSF recruits CoREST and mSin3A corepressors to
      stem cell chromatin for the regulation of pro-neuronal target genes to prevent
      precocious neuronal differentiation in cultured adult NSCs. Moreover, mice
      lacking REST/NRSF specifically in NSCs display a transient increase in adult
      neurogenesis that leads to a loss in the neurogenic capacity of NSCs and
      eventually diminished granule neurons. Our work identifies REST/NRSF as a master
      negative regulator of adult NSC differentiation and offers a potential molecular
      target for neuroregenerative approaches.

PMID- 21715645
TI  - Neighborhood socioeconomic context and cognitive decline among older Mexican
      Americans: results from the Sacramento Area Latino Study on Aging.
AB  - In 1 previous study, it was shown that neighborhood socioeconomic disadvantage is
      associated with cognitive decline among Latinos. No studies have explored whether
      and to what extent individual-level socioeconomic factors account for the
      relation between neighborhood disadvantage and cognitive decline. The purpose of
      the present study was to assess the influence of neighborhood socioeconomic
      position (SEP) on cognitive decline and examine how individual-level SEP factors
      (educational level, annual income, and occupation) influenced neighborhood
      associations over the course of 10 years. Participants (n = 1,789) were community
      dwelling older Mexican Americans from the Sacramento Area Latino Study on Aging.
      Neighborhood SEP was derived by linking the participant's individual data to the
      2000 decennial census. The authors assessed cognitive function with the Modified
      Mini-Mental State Examination. Analyses used 3-level hierarchical linear mixed
      models of time within individuals within neighborhoods. After adjustment for
      individual-level sociodemographic characteristics, higher neighborhood SEP was
      significantly associated with cognitive function (beta = -0.033; P < 0.05) and
      rates of decline (beta = -0.0009; P < 0.10). After adjustment for individual
      educational level, neighborhood SEP remained associated with baseline cognition
      but not with rates of decline. Differences in individual educational levels
      explained most of the intra- and interneighborhood variance. These results
      suggest that the effect of neighborhood SEP on cognitive decline among Latinos is
      primarily accounted for by education.

PMID- 21715646
TI  - The rising relative risk of mortality for singles: meta-analysis and meta
      regression.
AB  - Never-married persons (singles) constitute a growing demographic group; yet, the
      magnitude of the all-cause relative mortality risk for nonelderly singles is not
      known and important moderating factors have not been explored. The authors used
      meta-analysis to examine 641 risk estimates from 95 publications that provided
      data on more than 500 million persons. The comparison group consisted of
      currently married individuals. The mean hazard ratio for mortality was 1.24 (95%
      confidence interval: 1.19, 1.30) among multivariate-adjusted hazard ratios with a
      high subjective quality rating. Meta-regressions showed that hazard ratios have
      been modestly increasing over time for both genders, but have done so somewhat
      more rapidly for women. The results also showed that the hazard ratio decreased
      with age and that study quality has an important relation to hazard ratio
      magnitude.

PMID- 21715647
TI  - Validation of new measures of disability and functioning in the National Health
      and Aging Trends Study.
AB  - BACKGROUND: Measurement gaps continue to hamper fuller understanding of late-life
      disability trends and dynamics. This article reports findings that validate the
      self-reported components of the disability protocol to be used in the new
      National Health and Aging Trends Study. The protocol was designed to redress
      existing measures by attending to environmental aspects of disability, capturing
      a broader range of capacity to perform tasks and including participation
      restriction items. METHODS: We undertook an in-person validation study to
      determine the reliability, validity, and initial measurement properties of the
      National Health and Aging Trends Study self-reported disability protocol (n =
      326). A random subset (n = 111) was readministered the protocol within 2-4 weeks.
      The interview and reinterview included new self-reported measures of physical
      capacity, activity limitations, and participation restrictions, as well as
      established performance and cognitive tests. We calculated percent agreement and
      kappa between interviews for all self-reported items and summary measures. We
      also assessed the construct validity of summary measures through correlations
      with demographic characteristics, frailty, memory, and performance-based mobility
      and confirmed whether activity limitations and participation restrictions were
      distinct domains. RESULTS: New items and derived summary measures demonstrate
      robustness over a short time period, with kappas for retained/recommended items
      in the .60-.80 range. The summary measures correlate as expected with age, sex,
      residential status, and established performance-based constructs. Two factors,
      representing activity limitations and participation restrictions, were confirmed.
      CONCLUSIONS: The National Health and Aging Trends Study protocol preserves the
      ability to examine more traditional measures of functioning while offering new
      insights into how activities are performed and preserving key conceptual
      distinctions.

PMID- 21715648
TI  - Adaptations in capillarization and citrate synthase activity in response to
      endurance training in older and young men.
AB  - The time-course of adaptation in cardiorespiratory fitness, measures of
      capillarization, and citrate synthase (CS) activity were examined in seven older
      (O; 69 +/- 7 years) and seven young (Y; 22 +/- 1 years) men pre-, mid-, and
      posttraining during a 12-week endurance training program. Training was performed
      on a cycle ergometer three times per week for 45 minutes at ~70% of maximal VO(2)
      (VO(2max)). VO(2max) and maximal cardiac output increased similarly from pre- to
      posttraining in O and Y (p < .05), and maximal a-vO(2diff) was greater (p < .05)
      posttraining in O and Y. CS was elevated at mid- and posttraining compared with
      pretraining in both O and Y (p < .05). Indices of capillarization increased 30%
      40% in O and 20%-30% in Y and were elevated at posttraining compared with pre-
      and midtraining in both groups (p < .05). This study showed that both O and Y
      undertaking similar endurance training displayed capillary angiogenesis and
      improved mitochondrial respiratory capacity.

PMID- 21715649
TI  - Is ABP1 an auxin receptor yet?
AB  - AUXIN BINDING PROTEIN 1 (ABP1) has long been proposed as an auxin receptor to
      regulate cell expansion. The embryo lethality of ABP1-null mutants demonstrates
      its fundamental role in plant development, but also hinders investigation of its
      involvement in post-embryonic processes and its mode of action. By taking
      advantage of weak alleles and inducible systems, several recent studies have
      revealed a role for ABP1 in organ development, cell polarization, and shape
      formation. In addition to its role in the regulation of auxin-induced gene
      expression, ABP1 has now been shown to modulate non-transcriptional auxin
      responses. ABP1 is required for activating two antagonizing ROP GTPase signaling
      pathways involved in cytoskeletal reorganization and cell shape formation, and
      participates in the regulation of clathrin-mediated endocytosis to subsequently
      affect PIN protein distribution. These exciting discoveries provide indisputable
      evidence for the auxin-induced signaling pathways that are downstream of ABP1
      function, and suggest intriguing mechanisms for ABP1-mediated polar cell
      expansion and spatial coordination in response to auxin.

PMID- 21715650
TI  - Arabidopsis MSBP1 is activated by HY5 and HYH and is involved in
      photomorphogenesis and brassinosteroid sensitivity regulation.
AB  - Membrane Steroid Binding Protein 1 (MSBP1) can bind steroids in vitro and
      negatively regulates brassinosteroid (BR) signaling, as well as cell elongation
      and expansion. Detailed analysis of the MSBP1 expression pattern based on
      quantitative real-time RT-PCR and promoter-GUS fusion studies revealed that MSBP1
      expression in hypocotyls is stimulated by various light conditions.
      Interestingly, MSBP1 expression is greatly suppressed in hy5, hyh, or hy5 hyh
      mutants but enhanced in cop1 mutants. Further analysis employing a yeast one
      hybrid assay, an electrophoretic mobility shift assay (EMSA), and a Chromatin IP
      (ChIP) assay confirmed the direct binding of Long Hypocotyl 5 (HY5) and HY5
      Homolog (HYH) to the promoter region of MSBP1, indicating that MSBP1 is involved
      in light-regulated hypocotyl growth by serving as a direct target for HY5 and
      HYH. In addition, hy5 and hy5 hyh mutants show altered BR responses to light,
      which is consistent with the suppressed expression of MSBP1 in these mutants.
      These results suggest that light triggers MSBP1 expression through direct binding
      to and activation by HY5 and HYH, thereby inhibiting hypocotyl elongation. The
      findings also provide informative clues regarding the mechanisms for the negative
      regulation of BR sensitivity and photomorphogenesis during the dark-light
      transition.

PMID- 21715651
TI  - Connectivity between perisylvian and bilateral basal temporal cortices.
AB  - Language processing requires the orchestrated action of different neuronal
      populations, and some studies suggest that the role of the basal temporal (BT)
      cortex in language processing is bilaterally distributed. Our aim was to
      demonstrate connectivity between perisylvian cortex and both BT areas. We
      recorded corticocortical evoked potentials (CCEPs) in 8 patients with subdural
      electrodes implanted for surgical evaluation of intractable epilepsy. Four
      patients had subdural grids over dominant perisylvian and BT areas, and 4 had
      electrode strips over both BT areas and left posterior superior temporal gyrus
      (LPSTG). After electrocortical mapping, patients with grids had 1-Hz stimulation
      of language areas. Patients with strips did not undergo mapping but had 1-Hz
      stimulation of the LPSTG. Posterior language area stimulation elicited CCEPs in
      ipsilateral BT cortex in 3/4 patients with left hemispheric grids. CCEPs were
      recorded in bilateral BT cortices in 3/4 patients with strips upon stimulation of
      the LPSTG, and in the LPSTG in the fourth patient upon stimulation of either BT
      area. This is the first in vivo demonstration of connectivity between LPSTG and
      both BT cortices. The role of BT cortex in language processing may be bilaterally
      distributed and related to linking visual information with phonological
      representations stored in the LPSTG.

PMID- 21715652
TI  - Which types of televised anti-tobacco campaigns prompt more quitline calls from
      disadvantaged groups?
AB  - To examine the efficacy of different types of mass media ads in driving lower
      socio-economic smokers (SES) to utilize quitlines. This study collected all 33
      719 calls to the Victorian quitline in Australia over a 2-year period. Negative
      binomial regressions examined the relationship between weekly levels of exposure
      to different types of anti-smoking ads and quitline calls, after adjusting for
      covariates. Interaction terms were added to determine whether relationships
      differed by SES. In total, smokers were exposed 88.39 times to anti-smoking ads
      over the 2-year period, as estimated by target audience ratings points. Higher
      emotion narrative ad exposure had the strongest association with quitline calls,
      increasing call rates by 13% for every additional ad exposure per week (per 100
      points, rate ratio = 1.132, P = 0.001). Substantially, greater increases in calls
      to quitline from lower SES groups were observed when higher emotion narrative ads
      were on air compared with when other ad types were on air, and this advantage was
      not as strong among higher SES groups. Airing higher emotion narrative anti
      smoking ads may contribute to reducing, but not eliminating, socio-economic
      disparities in calls to the quitline through maximizing the responses of the
      lower SES smokers.

PMID- 21715653
TI  - A brief structured education programme enhances self-care practices and improves
      glycaemic control in Malaysians with poorly controlled diabetes.
AB  - We assessed the effectiveness of a brief structured diabetes education programme
      based on the concept of self-efficacy on self-care and glycaemic control using
      single-blind study design. One hundred and sixty-four participants with poorly
      controlled diabetes from two settings were randomized using computer-generated
      list into control (n = 82) and intervention (n = 82) groups, of which 151
      completed the study. Monthly interventions over 12 weeks addressed the self-care
      practices of diet, physical activity, medication adherence and self-monitoring of
      blood glucose (SMBG). These self-care practices were assessed at Weeks 0 and 12
      using pre- and post-questionnaires in both groups together with glycated
      haemoglobin A1c (HbA1c) and diabetes knowledge. In the intention-to-treat
      analysis (n = 164), the intervention group improved their SMBG (P = <0.001),
      physical activity (P = 0.001), HbA1c (P = 0.03), diabetes knowledge (P = <0.001)
      and medication adherence. At Week 12, HbA1c difference adjusted for SMBG
      frequency, medication adherence and weight change remained significant (P = 0.03)
      compared with control group. For within group comparisons, diabetes knowledge (P
      = <0.001), HbA1c level (P = <0.001), SMBG (P = <0.001) and medication adherence
      (P = 0.008) improved from baseline in the intervention group. In the control
      group, only diabetes knowledge improved (P = <0.001). These findings can
      contribute to the development of self-management diabetes education in Malaysia.

PMID- 21715654
TI  - Homeodomain transcription factor and tumor suppressor Prep1 is required to
      maintain genomic stability.
AB  - Prep1 is a homeodomain transcription factor that is essential in embryonic
      development and functions in the adult as a tumor suppressor. We show here that
      Prep1 is involved in maintaining genomic stability and preventing neoplastic
      transformation. Hypomorphic homozygous Prep1(i/i) fetal liver cells and mouse
      embryonic fibroblasts (MEFs) exhibit increased basal DNA damage and normal DNA
      damage response after gamma-irradiation compared with WT. Cytogenetic analysis
      shows the presence of numerous chromosomal aberrations and aneuploidy in very
      early-passage Prep1(i/i) MEFs. In human fibroblasts, acute Prep1 down-regulation
      by siRNA induces DNA damage response, like in Prep1(i/i) MEFs, together with an
      increase in heterochromatin-associated modifications: rapid increase of histone
      methylation and decreased transcription of satellite DNA. Ectopic expression of
      Prep1 rescues DNA damage and heterochromatin methylation. Inhibition of Suv39
      activity blocks the chromatin but not the DNA damage phenotype. Finally, Prep1
      deficiency facilitates cell immortalization, escape from oncogene-induced
      senescence, and H-Ras(V12)-dependent transformation. Importantly, the latter can
      be partially rescued by restoration of Prep1 level. The results show that the
      tumor suppressor role of Prep1 is associated with the maintenance of genomic
      stability.

PMID- 21715655
TI  - IL-2R common gamma-chain is epigenetically silenced by nucleophosphin-anaplastic
      lymphoma kinase (NPM-ALK) and acts as a tumor suppressor by targeting NPM-ALK.
AB  - Anaplastic lymphoma kinase (ALK), physiologically expressed only by certain
      neural cells, becomes highly oncogenic, when aberrantly expressed in nonneural
      tissues as a fusion protein with nucleophosphin (NPM) and other partners. The
      reason why NPM-ALK succeeds in transforming specifically CD4(+) T lymphocytes
      remains unknown. The IL-2R common gamma-chain (IL-2Rgamma) is shared by receptors
      for several cytokines that play key roles in the maturation and growth of normal
      CD4(+) T lymphocytes and other immune cells. We show that IL-2Rgamma expression
      is inhibited in T-cell lymphoma cells expressing NPM-ALK kinase as a result of
      DNA methylation of the IL-2Rgamma gene promoter. IL-2Rgamma promoter methylation
      is induced in malignant T cells by NPM-ALK. NPM-ALK acts through STAT3, a
      transcription factor that binds to the IL-2Rgamma gene promoter and enhances
      binding of DNA methyltransferases (DNMTs) to the promoter. In addition, STAT3
      suppresses expression of miR-21, which selectively inhibits DNMT1 mRNA
      expression. Reconstitution of IL-2Rgamma expression leads to loss of the NPM-ALK
      protein and, consequently, apoptotic cell death of the lymphoma cells. These
      results demonstrate that the oncogenic tyrosine kinase NPM-ALK induces epigenetic
      silencing of the IL-2Rgamma gene and that IL-2Rgamma acts as a tumor suppressor
      by reciprocally inhibiting expression of NPM-ALK.

PMID- 21715656
TI  - A yeast-based assay identifies drugs active against human mitochondrial
      disorders.
AB  - Due to the lack of relevant animal models, development of effective treatments
      for human mitochondrial diseases has been limited. Here we establish a rapid,
      yeast-based assay to screen for drugs active against human inherited
      mitochondrial diseases affecting ATP synthase, in particular NARP (neuropathy,
      ataxia, and retinitis pigmentosa) syndrome. This method is based on the
      conservation of mitochondrial function from yeast to human, on the unique ability
      of yeast to survive without production of ATP by oxidative phosphorylation, and
      on the amenability of the yeast mitochondrial genome to site-directed
      mutagenesis. Our method identifies chlorhexidine by screening a chemical library
      and oleate through a candidate approach. We show that these molecules rescue a
      number of phenotypes resulting from mutations affecting ATP synthase in yeast.
      These compounds are also active on human cybrid cells derived from NARP patients.
      These results validate our method as an effective high-throughput screening
      approach to identify drugs active in the treatment of human ATP synthase
      disorders and suggest that this type of method could be applied to other
      mitochondrial diseases.

PMID- 21715657
TI  - Genome-wide profiling of diel and circadian gene expression in the malaria vector
      Anopheles gambiae.
AB  - Anopheles gambiae, the primary African vector of malaria parasites, exhibits
      numerous rhythmic behaviors including flight activity, swarming, mating, host
      seeking, egg laying, and sugar feeding. However, little work has been performed
      to elucidate the molecular basis for these daily rhythms. To study how gene
      expression is regulated globally by diel and circadian mechanisms, we have
      undertaken a DNA microarray analysis of An. gambiae under light/dark cycle (LD)
      and constant dark (DD) conditions. Adult mated, non-blood-fed female mosquitoes
      were collected every 4 h for 48 h, and samples were processed with DNA
      microarrays. Using a cosine wave-fitting algorithm, we identified 1,293 and 600
      rhythmic genes with a period length of 20-28 h in the head and body,
      respectively, under LD conditions, representing 9.7 and 4.5% of the An. gambiae
      gene set. A majority of these genes was specific to heads or bodies. Examination
      of mosquitoes under DD conditions revealed that rhythmic programming of the
      transcriptome is dependent on an interaction between the endogenous clock and
      extrinsic regulation by the LD cycle. A subset of genes, including the canonical
      clock components, was expressed rhythmically under both environmental conditions.
      A majority of genes had peak expression clustered around the day/night
      transitions, anticipating dawn and dusk. Genes cover diverse biological processes
      such as transcription/translation, metabolism, detoxification, olfaction, vision,
      cuticle regulation, and immunity, and include rate-limiting steps in the
      pathways. This study highlights the fundamental roles that both the circadian
      clock and light play in the physiology of this important insect vector and
      suggests targets for intervention.

PMID- 21715659
TI  - Suppression of cytokine storm with a sphingosine analog provides protection
      against pathogenic influenza virus.
AB  - Human pandemic H1N1 2009 influenza virus rapidly infected millions worldwide and
      was associated with significant mortality. Antiviral drugs that inhibit influenza
      virus replication are the primary therapy used to diminish disease; however,
      there are two significant limitations to their effective use: (i) antiviral drugs
      exert selective pressure on the virus, resulting in the generation of more fit
      viral progeny that are resistant to treatment; and (ii) antiviral drugs do not
      directly inhibit immune-mediated pulmonary injury that is a significant component
      of disease. Here we show that dampening the host's immune response against
      influenza virus using an immunomodulatory drug, AAL-R, provides significant
      protection from mortality (82%) over that of the neuraminidase inhibitor
      oseltamivir alone (50%). AAL-R combined with oseltamivir provided maximum
      protection against a lethal challenge of influenza virus (96%). Mechanistically,
      AAL-R inhibits cellular and cytokine/chemokine responses to limit
      immunopathologic damage, while maintaining host control of virus replication.
      With cytokine storm playing a role in the pathogenesis of a wide assortment of
      viral, bacterial, and immunologic diseases, a therapeutic approach using
      sphingosine analogs is of particular interest.

PMID- 21715660
TI  - Unravelling evolutionary strategies of yeast for improving galactose utilization
      through integrated systems level analysis.
AB  - Identification of the underlying molecular mechanisms for a derived phenotype by
      adaptive evolution is difficult. Here, we performed a systems-level inquiry into
      the metabolic changes occurring in the yeast Saccharomyces cerevisiae as a result
      of its adaptive evolution to increase its specific growth rate on galactose and
      related these changes to the acquired phenotypic properties. Three evolved
      mutants (62A, 62B, and 62C) with higher specific growth rates and faster specific
      galactose uptake were isolated. The evolved mutants were compared with a
      reference strain and two engineered strains, SO16 and PGM2, which also showed
      higher galactose uptake rate in previous studies. The profile of intermediates in
      galactose metabolism was similar in evolved and engineered mutants, whereas
      reserve carbohydrates metabolism was specifically elevated in the evolved mutants
      and one evolved strain showed changes in ergosterol biosynthesis. Mutations were
      identified in proteins involved in the global carbon sensing Ras/PKA pathway,
      which is known to regulate the reserve carbohydrates metabolism. We evaluated one
      of the identified mutations, RAS2(Tyr112), and this mutation resulted in an
      increased specific growth rate on galactose. These results show that adaptive
      evolution results in the utilization of unpredicted routes to accommodate
      increased galactose flux in contrast to rationally engineered strains. Our study
      demonstrates that adaptive evolution represents a valuable alternative to
      rational design in bioengineering of improved strains and, that through systems
      biology, it is possible to identify mutations in evolved strain that can serve as
      unforeseen metabolic engineering targets for improving microbial strains for
      production of biofuels and chemicals.

PMID- 21715661
TI  - Seeing protein monolayers with naked eye through plasmonic Fano resonances.
AB  - We introduce an ultrasensitive label-free detection technique based on asymmetric
      Fano resonances in plasmonic nanoholes with far reaching implications for point
      of-care diagnostics. By exploiting extraordinary light transmission phenomena
      through high-quality factor (Q(solution) ~ 200) subradiant dark modes, we
      experimentally demonstrate record high figures of merits (FOMs as high as 162)
      for intrinsic detection limits surpassing that of the gold standard prism coupled
      surface-plasmon sensors (Kretschmann configuration). Our experimental record high
      sensitivities are attributed to the nearly complete suppression of the radiative
      losses that are made possible by the high structural quality of the fabricated
      devices as well as the subradiant nature of the resonances. Steep dispersion of
      the plasmonic Fano resonance profiles in high-quality plasmonic sensors exhibit
      dramatic light intensity changes to the slightest perturbations within their
      local environment. As a spectacular demonstration of the extraordinary
      sensitivity and the quality of the fabricated biosensors, we show direct
      detection of a single monolayer of biomolecules with naked eye using these Fano
      resonances and the associated Wood's anomalies. To fabricate high optical-quality
      sensors, we introduce a high-throughput lift-off free evaporation fabrication
      technique with extremely uniform and precisely controlled nanofeatures over large
      areas, leading to resonance line-widths comparable to that of the ideally uniform
      structures as confirmed by our time-domain simulations. The demonstrated label
      free sensing platform offers unique opportunities for point-of-care diagnostics
      in resource poor settings by eliminating the need for fluorescent labeling and
      optical detection instrumentation (camera, spectrometer, etc.) as well as
      mechanical and light isolation.

PMID- 21715662
TI  - Localization of electrons due to orbitally ordered bi-stripes in the bilayer
      manganite La(2-2x)Sr(1+2x)Mn2O7 (x ~ 0.59).
AB  - Electronic phases with stripe patterns have been intensively investigated for
      their vital roles in unique properties of correlated electronic materials. How
      these real-space patterns affect the conductivity and other properties of
      materials (which are usually described in momentum space) is one of the major
      challenges of modern condensed matter physics. By studying the electronic
      structure of La(2-2x)Sr(1+2x)Mn(2)O(7) (x ~ 0.59) and in combination with earlier
      scattering measurements, we demonstrate the variation of electronic properties
      accompanying the melting of so-called bi-stripes in this material. The static bi
      stripes can strongly localize the electrons in the insulating phase above T(c) ~
      160 K, while the fraction of mobile electrons grows, coexisting with a
      significant portion of localized electrons when the static bi-stripes melt below
      T(c). The presence of localized electrons below T(c) suggests that the melting bi
      stripes exist as a disordered or fluctuating counterpart. From static to melting,
      the bi-stripes act as an atomic-scale electronic valve, leading to a "colossal"
      metal-insulator transition in this material.

PMID- 21715663
TI  - Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can
      be differentially prevented by alpha7 and beta2* nicotinic stimulation.
AB  - A good model of neuronal death that reproduces the characteristic tau (tau)
      hyperphosphorylation of Alzheimers disease is the use of okadaic acid (OA). The
      aim of this study was to determine the contribution of alpha7 and beta2*
      nicotinic acetylcholine receptor (nAChR) subtypes to neuroprotection against OA
      in the SH-SY5Y cell line by using the selective alpha7 and beta2* nAChR agonists
      PNU 282987 and 5-Iodo-A85380, respectively. The results of this study show that
      both alpha7 and beta2* nAChR can afford neuroprotection against OA-induced
      neurotoxicity. Protection mediated by alpha7 nAChRs was independent of Ca(2+) and
      involved the intracellular signaling pathway Janus Kinase-2/Phosphatidylinositol
      3-kinase/Akt. When Ca(2+) entry was promoted through the alpha7 nAChR by using
      the alpha7-selective positive allosteric modulator PNU 120596, protection was
      lost. By contrast, protection mediated by beta2* nAChRs was Ca(2+) dependent and
      implicated the signaling pathways PI3K/Akt and extracellular regulated kinase
      1/2. Both alpha7 and beta2* nAChR activation converged on downregulation of GSK
      3beta and reduction of tau phosphorylation in cells undergoing cell death induced
      by OA. Therefore, targeting nAChR could offer a strategy for reducing
      neurodegeneration secondary to hyperphosphorylation of protein tau.

PMID- 21715664
TI  - Deregulation of cancer-related pathways in primary hepatocytes derived from DNA
      repair-deficient Xpa-/-p53+/- mice upon exposure to benzo[a]pyrene.
AB  - The current method to predict carcinogenicity of chemicals or drugs is the
      chronic 2-year rodent bioassay, which has disadvantages in duration, animal use,
      and specificity. An attractive alternative is the DNA repair-deficient Xpa(-/
      )p53(+/-) mouse model that is sensitive to both genotoxic and nongenotoxic
      carcinogens. A next step in alternative carcinogenicity testing is the
      development of reliable in vitro systems. We investigated the use of primary
      hepatocytes, isolated from wild-type (WT) and Xpa(-/-)p53(+/-) mice, in
      combination with transcriptome analyses for their usefulness to predict
      carcinogenic features of compounds. As a proof of principle, we studied the
      response of hepatocytes to the genotoxic carcinogen benzo[a]pyrene (B[a]P). Upon
      treatment, both WT and Xpa(-/-)p53(+/-) hepatocytes appeared to be metabolically
      active. However, Xpa(-/-)p53(+/-) hepatocytes were more sensitive than WT
      hepatocytes to B[a]P treatment in terms of cell survival. In B[a]P-treated WT
      hepatocytes, DNA repair and cell cycle control genes were transcriptionally
      activated. Xpa(-/-)p53(+/-) hepatocytes were more responsive to B[a]P exposure,
      resulting in the downregulation of cancer-related pathways. Deregulation of
      mitogen-activated protein kinase signaling seems to play an essential role in
      this and might be the underlying reason for the increased susceptibility of Xpa(
      /-)p53(+/-) mice toward carcinogens. Our conclusion is that primary hepatocytes
      combined with transcriptomics are promising to identify the carcinogenic features
      of chemicals. Furthermore, these cells seem suitable to gain further insight into
      the molecular mechanisms of the increased sensitivity of Xpa(-/-)p53(+/-) mice
      toward both genotoxic and nongenotoxic carcinogens.

PMID- 21715665
TI  - Toxicological implications of modulation of gene expression by microRNAs.
AB  - MicroRNAs (miRNAs) are a large family of non-coding RNAs that are evolutionarily
      conserved, endogenous, and 21-23 nucleotides in length. miRNAs regulate gene
      expression by targeting messenger RNAs (mRNAs) by binding to complementary
      regions of transcripts to repress their translation or mRNA degradation. miRNAs
      are encoded by the genome, and more than 1000 human miRNAs have been identified
      so far. miRNAs are predicted to target ~60% of human mRNAs and are expressed in
      all animal cells and have fundamental roles in cellular responses to xenobiotic
      stresses, which affect a large range of physiological processes such as
      development, immune responses, metabolism, tumor formation as well as
      toxicological outcomes. Recently, many reports concerning miRNAs related to
      cancer have been published; however, the miRNA research in the metabolism of
      xenobiotics and endobiotics and in toxicology has only recently been established.
      This review describes the current knowledge on the miRNA-dependent regulation of
      drug-metabolizing enzymes and nuclear receptors and its potential toxicological
      implications. In this review, miRNAs with reference to target prediction,
      potential modulation of toxicology-related changes of miRNA expression, role of
      miRNA in immune-mediated drug-induced liver injury, miRNA in plasma as potential
      toxicological biomarkers, and relevance of miRNA-related genetic polymorphisms
      are discussed.

PMID- 21715666
TI  - Heteronymous reflex connections in human upper limb muscles in response to
      stretch of forearm muscles.
AB  - Torque motor produced stretch of upper limb muscles results in two distinct
      reflex peaks in the electromyographic activity. Whereas the short-latency reflex
      (SLR) response is mediated largely by the spinal monosynaptic reflex pathway, the
      longer-latency reflex (LLR) is suggested to involve a transcortical loop. For the
      SLRs, patterns of heteronymous monosynaptic Ia connections have been well-studied
      for a large number of muscles in the cat and in humans. For LLRs, information is
      available for perturbations to proximal joints, although the protocols for most
      of these studies did not focus on heteronymous connections. The main objective of
      the present study was to elicit both SLRs and LLRs in wrist flexors and extensors
      and to examine heteronymous connections from these muscles to elbow flexors
      (biceps brachii; BiBr) and extensors (triceps brachii; TriBr) and to selected
      distal muscles, including abductor pollicis longus (APL), first dorsal
      interosseous (FDI), abductor digiti minimi (ADM), and Thenars. The stretch of
      wrist flexors produced SLR and LLR peaks in APL, FDI, ADM, Thenars, and BiBr
      while simultaneously inducing inhibition of wrist extensors and TriBr. When wrist
      extensors were stretched, SLR and LLR peaks were observed in TriBr, whereas the
      primary wrist flexors, APL and BiBr, were inhibited; response patterns of FDI,
      ADM, and Thenars were less consistent. The main conclusions from the observed
      data are that: 1) as in the cat, afferents from wrist flexors and extensors make
      heteronymous connections with proximal and distal upper limb muscles; and 2) the
      strength of heteronymous connections is greater for LLRs than SLRs in the distal
      muscles, whereas the opposite is true for the proximal muscles. In the majority
      of observations, SLR and LLR excitatory peaks were observed together. However, on
      occasion, LLRs were observed without the SLR response in hand muscles when wrist
      extensors were stretched.

PMID- 21715667
TI  - Heuristically optimal path scanning for high-speed multiphoton circuit imaging.
AB  - Population dynamics of patterned neuronal firing are fundamental to information
      processing in the brain. Multiphoton microscopy in combination with calcium
      indicator dyes allows circuit dynamics to be imaged with single-neuron
      resolution. However, the temporal resolution of fluorescent measures is
      constrained by the imaging frequency imposed by standard raster scanning
      techniques. As a result, traditional raster scans limit the ability to detect the
      relative timing of action potentials in the imaged neuronal population. To
      maximize the speed of fluorescence measures from large populations of neurons
      using a standard multiphoton laser scanning microscope (MPLSM) setup, we have
      developed heuristically optimal path scanning (HOPS). HOPS optimizes the laser
      travel path length, and thus the temporal resolution of neuronal fluorescent
      measures, using standard galvanometer scan mirrors. Minimizing the scan path
      alone is insufficient for prolonged high-speed imaging of neuronal populations.
      Path stability and the signal-to-noise ratio become increasingly important
      factors as scan rates increase. HOPS addresses this by characterizing the scan
      mirror galvanometers to achieve prolonged path stability. In addition, the
      neuronal dwell time is optimized to sharpen the detection of action potentials
      while maximizing scan rate. The combination of shortest path calculation and
      minimization of mirror positioning time allows us to optically monitor a
      population of neurons in a field of view at high rates with single-spike
      resolution, ~ 125 Hz for 50 neurons and ~ 8.5 Hz for 1,000 neurons. Our approach
      introduces an accessible method for rapid imaging of large neuronal populations
      using traditional MPLSMs, facilitating new insights into neuronal circuit
      dynamics.

PMID- 21715668
TI  - Phase sensitivities, excitatory summation fields, and silent suppressive
      receptive fields of single neurons in the parastriate cortex of the cat.
AB  - We have recorded single-neuron activity from cytoarchitectonic area 18 of
      anesthetized (0.4-0.7% isoflurane in 65% N2O-35% O2 gaseous mixture) domestic
      cats. Neurons were identified as simple or complex on the basis of the ratios
      between the phase-variant (F1) component and the mean firing rate (F0) of spike
      responses to optimized (orientation, direction, spatial and temporal frequencies,
      size) high-contrast, luminance-modulated, sine-wave drifting gratings (simple:
      F1/F0 spike-response ratios > 1; complex: F1/F0 spike-response ratios < 1). The
      predominance (~80%) of simple cells among the neurons recorded from the principal
      thalamorecipient layers supports the idea that most simple cells in area 18 might
      constitute a putative early stage in the visual information processing. Apart
      from the "spike-generating" regions (the classical receptive fields, CRFs), the
      receptive fields of three-quarters of area 18 neurons contain silent,
      extraclassical suppressive regions (ECRFs). The spatial extent of summation areas
      of excitatory responses was negatively correlated with the strength of the ECRF
      induced suppression of spike responses. Lowering the stimulus contrast resulted
      in an expansion of the summation areas of excitatory responses accompanied by a
      reduction in the strength of the ECRF-induced suppression. The spatial and
      temporal frequency and orientation tunings of the ECRFs were much broader than
      those of the CRFs. Hence, the ECRFs of area 18 neurons appear to be largely
      "inherited" from their dorsal thalamic inputs. In most area 18 cells,
      costimulation of CRFs and ECRFs resulted in significant increases in F1/F0 spike
      response ratios, and thus there was a contextually modulated functional continuum
      between the simple and complex cells.

PMID- 21715669
TI  - Quick phases control ocular torsion during smooth pursuit.
AB  - One of the open questions in oculomotor control of visually guided eye movements
      is whether it is possible to smoothly track a target along a curvilinear path
      across the visual field without changing the torsional stance of the eye. We show
      in an experimental study of three-dimensional eye movements in subhuman primates
      (Macaca mulatta) that although the pursuit system is able to smoothly change the
      orbital orientation of the eye's rotation axis, the smooth ocular motion was
      interrupted every few hundred milliseconds by a small quick phase with amplitude
      <1.5 degrees  while the animal tracked a target along a circle or ellipse.
      Specifically, during circular pursuit of targets moving at different angular
      eccentricities (5 degrees , 10 degrees , and 15 degrees ) relative to straight
      ahead at spatial frequencies of 0.067 and 0.1 Hz, the torsional amplitude of the
      intervening quick phases was typically around 1 degrees  or smaller and changed
      direction for clockwise vs. counterclockwise tracking. Reverse computations of
      the eye rotation based on the recorded angular eye velocity showed that the quick
      phases facilitate the overall control of ocular orientation in the roll plane,
      thereby minimizing torsional disturbances of the visual field. On the basis of a
      detailed kinematic analysis, we suggest that quick phases during curvilinear
      smooth tracking serve to minimize deviations from Donders' law, which are
      inevitable due to the spherical configuration space of smooth eye movements.

PMID- 21715670
TI  - Evoked potentials in large-scale cortical networks elicited by TMS of the visual
      cortex.
AB  - Single pulses of transcranial magnetic stimulation (TMS) result in distal and
      long-lasting oscillations, a finding directly challenging the virtual lesion
      hypothesis. Previous research supporting this finding has primarily come from
      stimulation of the motor cortex. We have used single-pulse TMS with simultaneous
      EEG to target seven brain regions, six of which belong to the visual system [left
      and right primary visual area V1, motion-sensitive human middle temporal cortex,
      and a ventral temporal region], as determined with functional MRI-guided
      neuronavigation, and a vertex "control" site to measure the network effects of
      the TMS pulse. We found the TMS-evoked potential (TMS-EP) over visual cortex
      consists mostly of site-dependent theta- and alphaband oscillations. These site
      dependent oscillations extended beyond the stimulation site to functionally
      connected cortical regions and correspond to time windows where the EEG responses
      maximally diverge (40, 200, and 385 ms). Correlations revealed two site
      independent oscillations ~350 ms after the TMS pulse: a theta-band oscillation
      carried by the frontal cortex, and an alpha-band oscillation over parietal and
      frontal cortical regions. A manipulation of stimulation intensity at one
      stimulation site (right hemisphere V1-V3) revealed sensitivity to the stimulation
      intensity at different regions of cortex, evidence of intensity tuning in regions
      distal to the site of stimulation. Together these results suggest that a TMS
      pulse applied to the visual cortex has a complex effect on brain function,
      engaging multiple brain networks functionally connected to the visual system with
      both invariant and site-specific spatiotemporal dynamics. With this
      characterization of TMS, we propose an alternative to the virtual lesion
      hypothesis. Rather than a technique that simulates lesions, we propose TMS
      generates natural brain signals and engages functional networks.

PMID- 21715671
TI  - Selectivity of pyramidal cells and interneurons in the human medial temporal
      lobe.
AB  - Neurons in the medial temporal lobe (MTL) respond selectively to pictures of
      specific individuals, objects, and places. However, the underlying mechanisms
      leading to such degree of stimulus selectivity are largely unknown. A necessary
      step to move forward in this direction involves the identification and
      characterization of the different neuron types present in MTL circuitry. We show
      that putative principal cells recorded in vivo from the human MTL are more
      selective than putative interneurons. Furthermore, we report that putative
      hippocampal pyramidal cells exhibit the highest degree of selectivity within the
      MTL, reflecting the hierarchical processing of visual information. We interpret
      these differences in selectivity as a plausible mechanism for generating sparse
      responses.

PMID- 21715672
TI  - The jasmonate pathway is a key player in systemically induced defense against
      root knot nematodes in rice.
AB  - Complex defense signaling pathways, controlled by different hormones, are
      involved in the reaction of plants to a wide range of biotic and abiotic stress
      factors. We studied the ability of salicylic acid, jasmonate (JA), and ethylene
      (ET) to induce systemic defense in rice (Oryza sativa) against the root knot
      nematode Meloidogyne graminicola. Exogenous ET (ethephon) and JA (methyl
      jasmonate) supply on the shoots induced a strong systemic defense response in the
      roots, exemplified by a major up-regulation of pathogenesis-related genes OsPR1a
      and OsPR1b, while the salicylic acid analog BTH (benzo-1,2,3-thiadiazole-7
      carbothioic acid S-methyl ester) was a less potent systemic defense inducer from
      shoot to root. Experiments with JA biosynthesis mutants and ET-insensitive
      transgenics showed that ET-induced defense requires an intact JA pathway, while
      JA-induced defense was still functional when ET signaling was impaired.
      Pharmacological inhibition of JA and ET biosynthesis confirmed that JA
      biosynthesis is needed for ET-induced systemic defense, and quantitative real
      time reverse transcription-polymerase chain reaction data revealed that ET
      application onto the shoots strongly activates JA biosynthesis and signaling
      genes in the roots. All data provided in this study point to the JA pathway to
      play a pivotal role in rice defense against root knot nematodes. The expression
      of defense-related genes was monitored in root galls caused by M. graminicola.
      Different analyzed defense genes were attenuated in root galls caused by the
      nematode at early time points after infection. However, when the exogenous
      defense inducers ethephon and methyl jasmonate were supplied to the plant, the
      nematode was less effective in counteracting root defense pathways, hence making
      the plant more resistant to nematode infection.

PMID- 21715673
TI  - Investigating the contribution of the phosphate transport pathway to arsenic
      accumulation in rice.
AB  - Arsenic (As) accumulation in rice (Oryza sativa) may pose a significant health
      risk to consumers. Plants take up different As species using various pathways.
      Here, we investigated the contribution of the phosphate (Pi) transport pathway to
      As accumulation in rice grown hydroponically or under flooded soil conditions. In
      hydroponic experiments, a rice mutant defective in OsPHF1 (for phosphate
      transporter traffic facilitator1) lost much of the ability to take up Pi and
      arsenate and to transport them from roots to shoots, whereas transgenic rice
      overexpressing either the Pi transporter OsPht1;8 (OsPT8) or the transcription
      factor OsPHR2 (for phosphate starvation response2) had enhanced abilities of Pi
      and arsenate uptake and translocation. OsPT8 was found to have a high affinity
      for both Pi and arsenate, and its overexpression increased the maximum influx by
      3- to 5-fold. In arsenate-treated plants, both arsenate and arsenite were
      detected in the xylem sap, with the proportion of the latter increasing with the
      exposure time. Under the flooded soil conditions, the phf1 mutant took up less Pi
      whereas the overexpression lines took up more Pi. But there were no similar
      effects on As accumulation and distribution. Rice grain contained predominantly
      dimethylarsinic acid and arsenite, with arsenate being a minor species. These
      results suggest that the Pi transport pathway contributed little to As uptake and
      transport to grain in rice plants grown in flooded soil. Transgenic approaches to
      enhance Pi acquisition from paddy soil through the overexpression of Pi
      transporters may not increase As accumulation in rice grain.

PMID- 21715674
TI  - Association between carbonyl sulfide uptake and (18)Delta during gas exchange in
      C(3) and C(4) leaves.
AB  - Carbonyl sulfide (COS) and C(18)OO exchange by leaves provide potentially
      powerful tracers of biosphere-atmosphere CO(2) exchange, and both are assumed to
      depend on carbonic anhydrase (CA) activity and conductance along the diffusive
      pathway in leaves. We investigated these links using C(3) and C(4) plants,
      hypothesizing that the rates of COS and C(18)OO exchange by leaves respond in
      parallel to environmental and biological drivers. Using CA-deficient antisense
      lines of C(4) and C(3) plants, COS uptake was essentially eliminated and
      discrimination against C(18)OO exchange ((18)Delta) greatly reduced,
      demonstrating CA's key role in both processes. (18)Delta showed a positive linear
      correlation with leaf relative uptake (LRU; ratio of COS to CO(2) assimilation
      rates, A(s)/A(c), normalized to their respective ambient concentrations), which
      reflected the effects of stomatal conductance on both COS and C(18)OO exchange.
      Unexpectedly, a decoupling between A(s) and (18)Delta was observed in comparing
      C(4) and C(3) plants, with a large decrease in (18)Delta but no parallel
      reduction in A(s) in the former. This could be explained by C(4) plants having
      higher COS concentrations at the CA site (maintaining high A(s) with reduced CA)
      and a high phosphoenolpyruvate carboxylase/CA activity ratio (reducing (18)O
      exchange efficiency between CO(2) and water, but not A(s)). Similar A(s) but
      higher A(c) in C(4) versus C(3) plants resulted in lower LRU values in the former
      (1.16 +/- 0.20 and 1.82 +/- 0.18 for C(4) and C(3), respectively). LRU was,
      however, relatively constant in both plant types across a wide range of
      conditions, except low light (<191 MUmol photon m(-2) s(-1)).

PMID- 21715675
TI  - The fiber of modern society.
AB  - A powerful perception that innovation has stagnated persists in the biomedical
      research community. In a series of Commentaries--three in this issue and more in
      future issues--diverse professionals engage in a critical dialogue on innovation
      that explores whether novel ideas continue to emerge and whether their
      implementation continues to create value. The authors also discuss ways to
      resuscitate innovation through new risk-benefit analyses, correction of funding
      follies, monitoring conflicts of interest, defining the roles of public and
      private institutions, and the teaching of innovation.

PMID- 21715676
TI  - Repaving the road to biomedical innovation through academia.
AB  - Biomedical innovation requires investigators to build on existing knowledge and
      achieve insights that are transformative. Innovation starts with incisive
      scientific discoveries, which are often made in academic research laboratories.
      Today, the financial model for supporting biomedical research in universities is
      threatened, and one victim is innovation. New models for public funding that
      support high-risk research in academia will spur innovation and ultimately
      advance clinical medicine.

PMID- 21715677
TI  - How to revive breakthrough innovation in the pharmaceutical industry.
AB  - Over the past 20 years, pharmaceutical companies have implemented conservative
      management practices to improve the predictability of therapeutics discovery and
      success rates of drug candidates. This approach has often yielded compounds that
      are only marginally better than existing therapies, yet require larger, longer,
      and more complex trials. To fund them, companies have shifted resources away from
      drug discovery to late clinical development; this has hurt innovation and
      amplified the crisis brought by the expiration of patents on many best-selling
      drugs. Here, we argue that more breakthrough therapeutics will reach patients
      only if the industry ceases to pursue "safe" incremental innovation, re-engages
      in high-risk discovery research, and adopts collaborative innovation models that
      allow sharing of knowledge and costs among collaborators.

PMID- 21715678
TI  - Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance.
AB  - The apolipoprotein E (APOE) epsilon4 allele is the strongest genetic risk factor
      for late-onset, sporadic Alzheimer's disease (AD). The APOE epsilon4 allele
      markedly increases AD risk and decreases age of onset, likely through its strong
      effect on the accumulation of amyloid-beta (Abeta) peptide. In contrast, the APOE
      epsilon2 allele appears to decrease AD risk. Most rare, early-onset forms of
      familial AD are caused by autosomal dominant mutations that often lead to
      overproduction of Abeta(42) peptide. However, the mechanism by which APOE alleles
      differentially modulate Abeta accumulation in sporadic, late-onset AD is less
      clear. In a cohort of cognitively normal individuals, we report that reliable
      molecular and neuroimaging biomarkers of cerebral Abeta deposition vary in an
      apoE isoform-dependent manner. We hypothesized that human apoE isoforms
      differentially affect Abeta clearance or synthesis in vivo, resulting in an apoE
      isoform-dependent pattern of Abeta accumulation later in life. Performing in vivo
      microdialysis in a mouse model of Abeta-amyloidosis expressing human apoE
      isoforms (PDAPP/TRE), we find that the concentration and clearance of soluble
      Abeta in the brain interstitial fluid depends on the isoform of apoE expressed.
      This pattern parallels the extent of Abeta deposition observed in aged PDAPP/TRE
      mice. ApoE isoform-dependent differences in soluble Abeta metabolism are observed
      not only in aged but also in young PDAPP/TRE mice well before the onset of Abeta
      deposition in amyloid plaques in the brain. Additionally, amyloidogenic
      processing of amyloid precursor protein and Abeta synthesis, as assessed by in
      vivo stable isotopic labeling kinetics, do not vary according to apoE isoform in
      young PDAPP/TRE mice. Our results suggest that APOE alleles contribute to AD risk
      by differentially regulating clearance of Abeta from the brain, suggesting that
      Abeta clearance pathways may be useful therapeutic targets for AD prevention.

PMID- 21715679
TI  - Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in
      Hutchinson-Gilford progeria syndrome cells.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder
      characterized by premature aging. HGPS is most commonly caused by a de novo
      single-nucleotide substitution in the lamin A/C gene (LMNA) that partially
      activates a cryptic splice donor site in exon 11, producing an abnormal lamin A
      protein termed progerin. Accumulation of progerin in dividing cells adversely
      affects the integrity of the nuclear scaffold and leads to nuclear blebbing in
      cultured cells. Progerin is also produced in normal cells, increasing in
      abundance as senescence approaches. Here, we report the effect of rapamycin, a
      macrolide antibiotic that has been implicated in slowing cellular and organismal
      aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin
      abolished nuclear blebbing, delayed the onset of cellular senescence, and
      enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the
      formation of insoluble progerin aggregates and induced clearance through
      autophagic mechanisms in normal fibroblasts. Our findings suggest an additional
      mechanism for the beneficial effects of rapamycin on longevity and encourage the
      hypothesis that rapamycin treatment could provide clinical benefit for children
      with HGPS.

PMID- 21715680
TI  - Allosteric interactions across native adenosine-A3 receptor homodimers:
      quantification using single-cell ligand-binding kinetics.
AB  - A growing awareness indicates that many G-protein-coupled receptors (GPCRs) exist
      as homodimers, but the extent of the cooperativity across the dimer interface has
      been largely unexplored. Here, measurement of the dissociation kinetics of a
      fluorescent agonist (ABA-X-BY630) from the human A(1) or A(3) adenosine receptors
      expressed in CHO-K1 cells has provided evidence for highly cooperative
      interactions between protomers of the A(3)-receptor dimer in single living cells.
      In the absence of competitive ligands, the dissociation rate constants of ABA-X
      BY630 from A(1) and A(3) receptors were 1.45 +/- 0.05 and 0.57 +/- 0.07 min(-1),
      respectively. At the A(3) receptor, this could be markedly increased by both
      orthosteric agonists and antagonists [15-, 9-, and 19-fold for xanthine amine
      congener (XAC), 5'-(N-ethyl carboxamido)adenosine (NECA), and adenosine,
      respectively] and reduced by coexpression of a nonbinding (N250A) A(3)-receptor
      mutant. The changes in ABA-X-BY630 dissociation were much lower at the A(1)
      receptor (1.5-, 1.4-, and 1.5-fold). Analysis of the pEC(50) values of XAC, NECA,
      and adenosine for the ABA-X-BY630-occupied A(3)-receptor dimer yielded values of
      6.0 +/- 0.1, 5.9 +/- 0.1, and 5.2 +/- 0.1, respectively. This study provides new
      insight into the spatial and temporal specificity of drug action that can be
      provided by allosteric modulation across a GPCR homodimeric interface.

PMID- 21715681
TI  - Response of chondrocytes to shear stress: antagonistic effects of the binding
      partners Toll-like receptor 4 and caveolin-1.
AB  - Osteoarthritis (OA) is often a consequence of excessive mechanical loading of
      cartilage, which produces hydrostatic stress, tensile strain, and fluid flow.
      Application of high fluid shear to chondrocytes recapitulates the earmarks of OA,
      as evidenced by the induction of cyclooxygenase-2, prostaglandins (PGs), and
      interleukin-6 (IL-6). Here, we delineated the signaling pathway by which high
      fluid shear mediates the temporal regulation of IL-6 synthesis in human
      chondrocytes. We determined that Toll-like receptor 4 (TLR4) and caveolin-1 are
      binding partners in chondrocytes. Their expression is temporally regulated by
      fluid shear via the sequential up-regulation of microsomal PGE synthase-1 (mPGES
      1) and L-PGDS. High shear stress rapidly induces an 8-fold up-regulation of TLR4
      expression via an mPGES-1-dependent pathway, whereas prolonged shear exposure
      concurrently down-regulates TLR4 by >4-fold and up-regulates caveolin-1
      expression by > 2.5-fold in an L-PGDS-dependent manner. TLR4 and caveolin-1 exert
      opposing effects on the activation of ERK1/2, PI3-K and PKA signaling pathways,
      which, in turn, regulate the NF-kappaB-dependent IL-6 synthesis in a time
      dependent fashion. Reconstructing the signaling network regulating shear-induced
      IL-6 expression in chondrocytes may provide insights for developing therapeutic
      strategies to combat osteoarthritis.

PMID- 21715682
TI  - Resveratrol prevents the wasting disorders of mechanical unloading by acting as a
      physical exercise mimetic in the rat.
AB  - Long-term spaceflight induces hypokinesia and hypodynamia, which, along
      microgravity per se, result in a number of significant physiological alterations,
      such as muscle atrophy, force reduction, insulin resistance, substrate use shift
      from fats to carbohydrates, and bone loss. Each of these adaptations could turn
      to serious health deterioration during the long-term spaceflight needed for
      planetary exploration. We hypothesized that resveratrol (RES), a natural
      polyphenol, could be used as a nutritional countermeasure to prevent muscle
      metabolic and bone adaptations to 15 d of rat hindlimb unloading. RES treatment
      maintained a net protein balance, soleus muscle mass, and soleus muscle maximal
      force contraction. RES also fully maintained soleus mitochondrial capacity to
      oxidize palmitoyl-carnitine and reversed the decrease of the glutathione vs.
      glutathione disulfide ratio, a biomarker of oxidative stress. At the molecular
      level, the protein content of Sirt-1 and COXIV in soleus muscle was also
      preserved. RES further protected whole-body insulin sensitivity and lipid
      trafficking and oxidation, and this was likely associated with the maintained
      expression of FAT/CD36, CPT-1, and peroxisome proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha) in muscle. Finally, chronic RES
      supplementation maintained the bone mineral density and strength of the femur.
      For the first time, we report a simple countermeasure that prevents the
      deleterious adaptations of the major physiological functions affected by
      mechanical unloading. RES could thus be envisaged as a nutritional countermeasure
      for spaceflight but remains to be tested in humans.

PMID- 21715683
TI  - CD8+ T cells primed in the periphery provide time-bound immune-surveillance to
      the central nervous system.
AB  - After vaccination, memory CD8(+) T cells migrate to different organs to mediate
      immune surveillance. In most nonlymphoid organs, following an infection, CD8(+) T
      cells differentiate to become long-lived effector-memory cells, thereby providing
      long-term protection against a secondary infection. In this study, we
      demonstrated that Ag-specific CD8(+) T cells that migrate to the mouse brain
      following a systemic Listeria infection do not display markers reminiscent of
      long-term memory cells. In contrast to spleen and other nonlymphoid organs, none
      of the CD8(+) T cells in the brain reverted to a memory phenotype, and all of the
      cells were gradually eliminated. These nonmemory phenotype CD8(+) T cells were
      found primarily within the choroid plexus, as well as in the cerebrospinal fluid
      filled spaces. Entry of these CD8(+) T cells into the brain was governed
      primarily by CD49d/VCAM-1, with the majority of entry occurring in the first week
      postinfection. When CD8(+) T cells were injected directly into the brain
      parenchyma, cells that remained in the brain retained a highly activated
      (CD69(hi)) phenotype and were gradually lost, whereas those that migrated out to
      the spleen were CD69(low) and persisted long-term. These results revealed a
      mechanism of time-bound immune surveillance to the brain by CD8(+) T cells that
      do not reside in the parenchyma.

PMID- 21715684
TI  - Regulation of chemerin chemoattractant and antibacterial activity by human
      cysteine cathepsins.
AB  - Chemerin, a ligand for the G-protein coupled receptor chemokine-like receptor 1,
      requires C-terminal proteolytic processing to unleash its chemoattractant
      activity. Proteolytically processed chemerin selectively attracts specific
      subsets of immunoregulatory APCs, including chemokine-like receptor 1-positive
      immature plasmacytoid dendritic cells (pDC). Chemerin is predicted to belong to
      the structural cathelicidin/cystatin family of proteins composed of antibacterial
      polypeptide cathelicidins and inhibitors of cysteine proteinases (cystatins). We
      therefore hypothesized that chemerin may interact directly with cysteine
      proteases, and that it might also function as an antibacterial agent. In this
      article, we show that chemerin does not inhibit human cysteine proteases, but
      rather is a new substrate for cathepsin (cat) K and L. cat K- and L-cleaved
      chemerin triggered robust migration of human blood-derived pDC ex vivo.
      Furthermore, cat K- and L-truncated chemerin also displayed antibacterial
      activity against Enterobacteriaceae. Cathepsins may therefore contribute to host
      defense by activating chemerin to directly inhibit bacterial growth and to
      recruit pDC to sites of infection.

PMID- 21715685
TI  - Different NK cell developmental events require different levels of IL-15 trans
      presentation.
AB  - NK cell development requires IL-15, which is "trans-presented" to IL-15Rbetagamma
      on NK cells by IL-15Ralpha on other cells. In this study, we report that
      different levels of IL-15 trans-presentation are required for different NK cell
      developmental events to reach full maturation status. Because the IL-15Ralpha
      intracellular domain has the capacity to recruit signaling molecules, we
      generated knockin and transgenic (Tg) mice that lack the intracellular domain to
      assess the role of the IL-15 trans-presentation level independent of the function
      of this domain. The level of IL-15Ralpha on various cells of these mice follows
      the order WT > Tg6 > knockin > Tg1 >= knockout. Bone marrow (BM)-derived
      dendritic cells prepared from these mice induced Stat5 phosphorylation in NK
      cells. The level of phospho-Stat5 correlated with the level of IL-15Ralpha on
      BMDCs, thus offering the opportunity to study quantitative effects of IL-15 trans
      presentation on NK cell development in vivo. We found that NK cell homeostasis,
      mature NK cell differentiation, and acquisition of Ly49 receptor and effector
      functions require different levels of IL-15 trans-presentation input to achieve
      full status. All NK cell developmental events examined were quantitatively
      regulated by the IL-15Ralpha level of BM-derived and radiation-resistant
      accessory cells, but not by IL-15Ralpha of NK cells. We also found that IL
      15Ralpha of radiation-resistant cells was more potent than IL-15Ralpha of BM
      derived accessory cells in support of stage 2 to stage 3 splenic mNK
      differentiation. In summary, each examined developmental event required a
      particular level of IL-15 trans-presentation by accessory cells.

PMID- 21715686
TI  - CD8+ T effector memory cells protect against liver-stage malaria.
AB  - Identification of correlates of protection for infectious diseases including
      malaria is a major challenge and has become one of the main obstacles in
      developing effective vaccines. We investigated protection against liver-stage
      malaria conferred by vaccination with adenoviral (Ad) and modified vaccinia
      Ankara (MVA) vectors expressing pre-erythrocytic malaria Ags. By classifying
      CD8(+) T cells into effector, effector memory (T(EM)), and central memory subsets
      using CD62L and CD127 markers, we found striking differences in T cell memory
      generation. Although MVA induced accelerated central memory T cell generation,
      which could be efficiently boosted by subsequent Ad administration, it failed to
      protect against malaria. In contrast, Ad vectors, which permit persistent Ag
      delivery, elicit a prolonged effector T cell and T(EM) response that requires
      long intervals for an efficient boost. A preferential T(EM) phenotype was
      maintained in liver, blood, and spleen after Ad/MVA prime-boost regimens, and
      animals were protected against malaria sporozoite challenge. Blood CD8(+) T(EM)
      cells correlated with protection against malaria liver-stage infection, assessed
      by estimation of number of parasites emerging from the liver into the blood. The
      protective ability of Ag-specific T(EM) cells was confirmed by transfer
      experiments into naive recipient mice. Thus, we identify persistent CD8 T(EM)
      populations as essential for vaccine-induced pre-erythrocytic protection against
      malaria, a finding that has important implications for vaccine design.

PMID- 21715687
TI  - CD28 expressed on malignant plasma cells induces a prosurvival and
      immunosuppressive microenvironment.
AB  - Interactions between the malignant plasma cells of multiple myeloma and stromal
      cells within the bone marrow microenvironment are essential for myeloma cell
      survival, mirroring the same dependence of normal bone marrow-resident long-lived
      plasma cells on specific marrow niches. These interactions directly transduce
      prosurvival signals to the myeloma cells and also induce niche production of
      supportive soluble factors. However, despite their central importance, the
      specific molecular and cellular components involved remain poorly characterized.
      We now report that the prototypic T cell costimulatory receptor CD28 is
      overexpressed on myeloma cells during disease progression and in the poor
      prognosis subgroups and plays a previously unrecognized role as a two-way
      molecular bridge to support myeloid stromal cells in the microenvironment.
      Engagement by CD28 to its ligand CD80/CD86 on stromal dendritic cell directly
      transduces a prosurvival signal to myeloma cell, protecting it against
      chemotherapy and growth factor withdrawal-induced death. Simultaneously, CD28
      mediated ligation of CD80/CD86 induces the stromal dendritic cell to produce the
      prosurvival cytokine IL-6 (involving novel cross-talk with the Notch pathway) and
      the immunosuppressive enzyme IDO. These findings identify CD28 and CD80/CD86 as
      important molecular components of the interaction between myeloma cells and the
      bone marrow microenvironment, point to similar interaction for normal plasma
      cells, and suggest novel therapeutic strategies to target malignant and
      pathogenic (e.g., in allergy and autoimmunity) plasma cells.

PMID- 21715688
TI  - The interaction between IL-18 and IL-18 receptor limits the magnitude of
      protective immunity and enhances pathogenic responses following infection with
      intracellular bacteria.
AB  - The binding of IL-18 to IL-18Ralpha induces both proinflammatory and protective
      functions during infection, depending on the context in which it occurs. IL-18 is
      highly expressed in the liver of wild-type (WT) C57BL/6 mice following lethal
      infection with highly virulent Ixodes ovatus ehrlichia (IOE), an obligate
      intracellular bacterium that causes acute fatal toxic shock-like syndrome. In
      this study, we found that IOE infection of IL-18Ralpha(-/-) mice resulted in
      significantly less host cell apoptosis, decreased hepatic leukocyte recruitment,
      enhanced bacterial clearance, and prolonged survival compared with infected WT
      mice, suggesting a pathogenic role for IL-18/IL-18Ralpha in Ehrlichia-induced
      toxic shock. Although lack of IL-18R decreased the magnitude of IFN-gamma
      producing type-1 immune response, enhanced resistance of IL-18Ralpha(-/-) mice
      against Ehrlichia correlated with increased proinflammatory cytokines at sites of
      infection, decreased systemic IL-10 production, increased frequency of protective
      NKT cells producing TNF-alpha and IFN-gamma, and decreased frequency of
      pathogenic TNF-alpha-producing CD8(+) T cells. Adoptive transfer of immune WT
      CD8(+) T cells increased bacterial burden in IL-18Ralpha(-/-) mice following IOE
      infection. Furthermore, rIL-18 treatment of WT mice infected with mildly virulent
      Ehrlichia muris impaired bacterial clearance and enhanced liver injury. Finally,
      lack of IL-18R signal reduced dendritic cell maturation and their TNF-alpha
      production, suggesting that IL-18 might promote the adaptive pathogenic immune
      responses against Ehrlichia by influencing T cell priming functions of dendritic
      cells. Together, these results suggested that the presence or absence of IL-18R
      signals governs the pathogenic versus protective immunity in a model of Ehrlichia
      induced immunopathology.

PMID- 21715690
TI  - Voltage-gated sodium channel Nav1.7 maintains the membrane potential and
      regulates the activation and chemokine-induced migration of a monocyte-derived
      dendritic cell subset.
AB  - Expression of CD1a protein defines a human dendritic cell (DC) subset with unique
      functional activities. We aimed to study the expression of the Nav1.7 sodium
      channel and the functional consequences of its activity in CD1a(-) and CD1a(+)
      DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments
      performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the
      frequency of cells expressing Na(+) current, current density, and the relative
      expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+)
      cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a
      depolarized resting membrane potential (-8.7 +/- 1.5 mV) in CD1a(+) IDC as
      compared with CD1a(-) cells lacking Nav1.7 (-47 +/- 6.2 mV). Stimulation of DC by
      inflammatory signals or by increased intracellular Ca(2+) levels resulted in
      reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane
      potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased
      cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin
      sensitized the cells for activation signals. Fine-tuning of IDC functions by a
      voltage-gated sodium channel emerges as a new regulatory mechanism modulating the
      migration and cytokine responses of these DC subsets.

PMID- 21715689
TI  - Importance of the CCR5-CCL5 axis for mucosal Trypanosoma cruzi protection and B
      cell activation.
AB  - Trypanosoma cruzi is an intracellular parasite and the causative agent of Chagas
      disease. Previous work has shown that the chemokine receptor CCR5 plays a role in
      systemic T. cruzi protection. We evaluated the importance of CCR5 and CCL5 for
      mucosal protection against natural oral and conjunctival T. cruzi challenges. T.
      cruzi-immune CCR5(-/-) and wild-type C57BL/6 mice were generated by repeated
      infectious challenges with T. cruzi. CCR5(-/-) and wild-type mice developed
      equivalent levels of cellular, humoral, and protective mucosal responses.
      However, CCR5(-/-)-immune mice produced increased levels of CCL5 in protected
      gastric tissues, suggesting compensatory signaling through additional receptors.
      Neutralization of CCL5 in CCR5(-/-)-immune mice resulted in decreased mucosal
      inflammatory responses, reduced T. cruzi-specific Ab-secreting cells, and
      significantly less mucosal T. cruzi protection, confirming an important role for
      CCL5 in optimal immune control of T. cruzi replication at the point of initial
      mucosal invasion. To investigate further the mechanism responsible for mucosal
      protection mediated by CCL5-CCR5 signaling, we evaluated the effects of CCL5 on B
      cells. CCL5 enhanced proliferation and IgM secretion in highly purified B cells
      triggered by suboptimal doses of LPS. In addition, neutralization of endogenous
      CCL5 inhibited B cell proliferation and IgM secretion during stimulation of
      highly purified B cells, indicating that B cell production of CCL5 has important
      autocrine effects. These findings demonstrate direct effects of CCL5 on B cells,
      with significant implications for the development of mucosal adjuvants, and
      further suggest that CCL5 may be important as a general B cell coactivator.

PMID- 21715691
TI  - Prostaglandin D2 regulates CD4+ memory T cell trafficking across blood vascular
      endothelium and primes these cells for clearance across lymphatic endothelium.
AB  - Memory lymphocytes support inflammatory and immune responses. To do this, they
      enter tissue via blood vascular endothelial cells (BVEC) and leave tissue via
      lymphatic vascular endothelial cells (LVEC). In this study, we describe a
      hierarchy of signals, including novel regulatory steps, which direct the
      sequential migration of human T cells across the blood and the lymphatic EC.
      Cytokine-stimulated (TNF and IFN) human BVEC preferentially recruited memory T
      cells from purified PBL. Lymphocyte recruitment from flow could be blocked using
      a function-neutralizing Ab against CXCR3. However, a receptor antagonist directed
      against the PGD(2) receptor DP2 (formerly chemoattractant receptor-homologous
      molecule expressed on Th2 cells) inhibited transendothelial migration,
      demonstrating that the sequential delivery of the chemokine and prostanoid
      signals was required for efficient lymphocyte recruitment. CD4(+) T cells
      recruited by BVEC migrated with significantly greater efficiency across a second
      barrier of human LVEC, an effect reproduced by the addition of exogenous PGD(2)
      to nonmigrated cells. Migration across BVEC or exogenous PGD(2) modified the
      function, but not the expression, of CCR7, so that chemotaxis toward CCL21 was
      significantly enhanced. Thus, chemokines may not regulate all stages of
      lymphocyte migration during inflammation, and paradigms describing their
      trafficking may need to account for the role of PGD(2).

PMID- 21715692
TI  - 4-1BB triggering ameliorates experimental autoimmune encephalomyelitis by
      modulating the balance between Th17 and regulatory T cells.
AB  - Agonistic anti-4-1BB Ab is known to ameliorate experimental autoimmune
      encephalomyelitis. 4-1BB triggering typically leads to the expansion of CD8(+) T
      cells, which produce abundant IFN-gamma, and this in turn results in IDO
      dependent suppression of autoimmune responses. However, because neutralization of
      IFN-gamma or depletion of CD8(+) T cell only partially abrogates the effect of 4
      1BB triggering, we sought to identify an additional mechanism of 4-1BB-triggered
      suppression of autoimmune responses using IFN-gamma- or IFN-gammaR-deficient
      mice. 4-1BB triggering inhibited the generation of Th17 cells that is responsible
      for experimental autoimmune encephalomyelitis induction and progression, and
      increased Foxp3(+)CD4(+) regulatory T (Treg) cells, particularly among CD4(+) T
      cells. This was not due to a direct effect of 4-1BB signaling on CD4(+) T cell
      differentiation: 4-1BB signaling not only reduced Th17 cells and increased Treg
      cells in wild-type mice, which could be due to IFN-gamma production by the CD8(+)
      T cells, but also did so in IFN-gamma-deficient mice, in that case by
      downregulating IL-6 production. These results show that although secondary
      suppressive mechanisms evoked by 4-1BB triggering are usually masked by the
      strong effects of IFN-gamma, 4-1BB signaling seems to modulate autoimmune
      responses by a number of mechanisms, and modulation of the Th17 versus Treg cell
      balance is one of those mechanisms.

PMID- 21715693
TI  - Cutting edge: dendritic cell-restricted antigen presentation initiates the
      follicular helper T cell program but cannot complete ultimate effector
      differentiation.
AB  - Follicular helper T (T(FH)) cells are critical for germinal center (GC)
      formation. The processes that drive their generation and effector potential
      remain unclear. In this study, we define requirements for MHC class II APCs in
      murine T(FH) cell formation by either transiently ablating or restricting Ag
      presentation to dendritic cells (DCs). We find that cognate interactions with DCs
      are necessary and sufficient to prime CD4(+) T cells toward a
      CXCR5(+)ICOS(+)Bcl6(+) T(FH) cell intermediate. However, in the absence of
      additional APCs, these T(FH) cells fail to produce IL-21. Furthermore, in vitro
      priming of naive T cells by B cells engenders optimal production of IL-21, which
      induces a GC B cell transcriptional profile. These results support a multistep
      model for effector T(FH) cell priming and GC initiation, in which DCs are
      necessary and sufficient to induce a T(FH) cell intermediate that requires
      additional interactions with distinct APCs for full effector function.

PMID- 21715694
TI  - Turning catabolism into usefulness: a jaundiced view.

PMID- 21715695
TI  - N-terminal pro-atrial natriuretic peptide measurement in plasma suggests covalent
      modification.
AB  - BACKGROUND: The N-terminal fragment of cardiac-derived pro-B-type natriuretic
      peptide is a glycosylated polypeptide. It is unknown whether N-terminal pro
      atrial natriuretic peptide (proANP) fragments are also covalently modified. We
      therefore evaluated the clinical performance of 2 distinctly different proANP
      assays on clinical outcome. METHODS: We examined 474 elderly patients with
      symptoms of heart failure presenting in a primary healthcare setting. Samples
      were analyzed with an automated immunoluminometric midregion proANP (MR-proANP)
      assay and a new processing-independent assay (PIA) developed in our laboratory.
      The results were compared with Bland-Altman plots, and clinical performance was
      assessed by generating ROC curves for different clinical outcomes. RESULTS:
      Despite linear regression results indicating a good correlation (r = 0.85; P <
      0.0001), the PIA measured considerably more proANP than the MR-proANP assay (mean
      difference, 663 pmol/L; SD, 478 pmol/L). In contrast, the clinical performances
      of the 2 assays [as assessed by the area under the ROC curve (AUC)] in detecting
      left ventricular dysfunction were similar [proANP PIA, 0.71 (95% CI, 0.63-0.79);
      MR-proANP assay, 0.74 (95% CI, 0.66-0.81); P = 0.32]. The prognostic ability to
      report cardiovascular mortality during a 10-year follow-up revealed AUC values of
      0.66 (95% CI, 0.60-0.71) for the proANP PIA and 0.69 (95% CI, 0.63-0.74) for the
      MR-proANP assay (P = 0.08, for comparing the 2 assays). CONCLUSIONS: Our data
      suggest that N-terminal proANP fragments in patient plasma differ from the
      calibrator peptides used but that the difference does not affect ROC curves in an
      elderly cohort of patients with mild to moderate heart failure. We suggest that
      human N-terminal proANP fragments can be covalently modified.

PMID- 21715696
TI  - Exercise reduces appetite and traffics excess nutrients away from energetically
      efficient pathways of lipid deposition during the early stages of weight regain.
AB  - The impact of regular exercise on energy balance, fuel utilization, and nutrient
      availability, during weight regain was studied in obese rats, which had lost 17%
      of their weight by a calorie-restricted, low-fat diet. Weight reduced rats were
      maintained for 6 wk with and without regular treadmill exercise (1 h/day, 6
      days/wk, 15 m/min). In vivo tracers and indirect calorimetry were then used in
      combination to examine nutrient metabolism during weight maintenance (in energy
      balance) and during the first day of relapse when allowed to eat ad libitum
      (relapse). An additional group of relapsing, sedentary rats were provided just
      enough calories to create the same positive energy imbalance as the relapsing,
      exercised rats. Exercise attenuated the energy imbalance by 50%, reducing
      appetite and increasing energy requirements. Expenditure increased beyond the
      energetic cost of the exercise bout, as exercised rats expended more energy to
      store the same nutrient excess in sedentary rats with the matched energy
      imbalance. Compared with sedentary rats with the same energy imbalance, exercised
      rats exhibited the trafficking of dietary fat toward oxidation and away from
      storage in adipose tissue, as well as a higher net retention of fuel via de novo
      lipogenesis in adipose tissue. These metabolic changes in relapse were preceded
      by an increase in the skeletal muscle expression of genes involved in lipid
      uptake, mobilization, and oxidation. Our observations reveal a favorable shift in
      fuel utilization with regular exercise that increases the energetic cost of
      storing excess nutrients during relapse and alterations in circulating nutrients
      that may affect appetite. The attenuation of the biological drive to regain
      weight, involving both central and peripheral aspects of energy homeostasis, may
      explain, in part, the utility of regular exercise in preventing weight regain
      after weight loss.

PMID- 21715697
TI  - The KATP channel Kir6.2 subunit content is higher in glycolytic than oxidative
      skeletal muscle fibers.
AB  - It has long been suggested that in skeletal muscle, the ATP-sensitive K(+)
      channel (K(ATP)) channel is important in protecting energy levels and that
      abolishing its activity causes fiber damage and severely impairs function. The
      responses to a lack of K(ATP) channel activity vary between muscles and fibers,
      with the severity of the impairment being the highest in the most glycolytic
      muscle fibers. Furthermore, glycolytic muscle fibers are also expected to face
      metabolic stress more often than oxidative ones. The objective of this study was
      to determine whether the t-tubular K(ATP) channel content differs between muscles
      and fiber types. K(ATP) channel content was estimated using a semiquantitative
      immunofluorescence approach by staining cross sections from soleus, extensor
      digitorum longus (EDL), and flexor digitorum brevis (FDB) muscles with anti
      Kir6.2 antibody. Fiber types were determined using serial cross sections stained
      with specific antimyosin I, IIA, IIB, and IIX antibodies. Changes in Kir6.2
      content were compared with changes in CaV1.1 content, as this Ca(2+) channel is
      responsible for triggering Ca(2+) release from sarcoplasmic reticulum. The Kir6.2
      content was the lowest in the oxidative soleus and the highest in the glycolytic
      EDL and FDB. At the individual fiber level, the Kir6.2 content within a muscle
      was in the order of type IIB > IIX > IIA >= I. Interestingly, the Kir6.2 content
      for a given fiber type was significantly different between soleus, EDL, and FDB,
      and highest in FDB. Correlations of relative fluorescence intensities from the
      Kir6.2 and CaV1.1 antibodies were significant for all three muscles. However, the
      variability in content between the three muscles or individual fibers was much
      greater for Kir6.2 than for CaV1.1. It is suggested that the t-tubular K(ATP)
      channel content increases as the glycolytic capacity increases and as the
      oxidative capacity decreases and that the expression of K(ATP) channels may be
      linked to how often muscles/fibers face metabolic stress.

PMID- 21715698
TI  - Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation
      in humans by decreasing ascorbate-sensitive oxidants.
AB  - Elevated low-density lipoproteins (LDL) are associated with cutaneous
      microvascular dysfunction partially mediated by increased arginase activity,
      which is decreased following a systemic atorvastatin therapy. We hypothesized
      that increased ascorbate-sensitive oxidant stress, partially mediated through
      uncoupled nitric oxide synthase (NOS) induced by upregulated arginase,
      contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC)
      humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177
      +/- 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin
      intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 +/- 4
      mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and
      arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin
      heating (42 degrees C) induced NO-dependent vasodilation. After the established
      plateau in all sites, 20 mM ?ngname? was infused to quantify NO-dependent
      vasodilation. Data were normalized to maximum cutaneous vascular conductance
      (CVC) (sodium nitroprusside + 43 degrees C). The plateau in vasodilation during
      local heating (HC: 78 +/- 4 vs. NC: 96 +/- 2% CVC(max), P < 0.01) and NO
      dependent vasodilation (HC: 40 +/- 4 vs. NC: 54 +/- 4% CVC(max), P < 0.01) was
      reduced in the HC group. Acute L-ascorbate alone (91 +/- 5% CVC(max), P < 0.001)
      or combined with arginase inhibition (96 +/- 3% CVC(max), P < 0.001) augmented
      the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96
      +/- 2; combo: 93 +/- 4% CVC(max), both P > 0.05). After the atorvastatin
      intervention NO-dependent vasodilation was augmented in the HC group (HC
      postatorvastatin: 64 +/- 4% CVC(max), P < 0.01), and there was no further effect
      of ascorbate alone (58 +/- 4% CVC(max,) P > 0.05) or combined with arginase
      inhibition (67 +/- 4% CVC(max,) P > 0.05). Increased ascorbate-sensitive oxidants
      contribute to hypercholesteromic associated cutaneous microvascular dysfunction
      which is partially reversed with atorvastatin therapy.

PMID- 21715699
TI  - Daily ethanol exposure during late ovine pregnancy: physiological effects in the
      mother and fetus in the apparent absence of overt fetal cerebral dysmorphology.
AB  - High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal
      development; however, the effects of lower levels of exposure are less clear. Our
      objectives were to assess the effects of daily EtOH exposure (3.8 USA standard
      drinks) on fetal-maternal physiological variables and the fetal brain,
      particularly white matter. Pregnant ewes received daily intravenous infusions of
      EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from
      95 to 133 days of gestational age (DGA; term ~145 DGA). Maternal and fetal
      arterial blood was sampled at 131-133 DGA. At necropsy (134 DGA) fetal brains
      were collected for analysis. Maternal and fetal plasma EtOH concentrations
      reached similar maximal concentration (~0.11 g/dl) and declined at the same rate.
      EtOH infusions produced mild reductions in fetal arterial oxygenation but there
      were no changes in maternal oxygenation, maternal and fetal Pa(CO(2)), or in
      fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma
      lactate levels were elevated in ewes and fetuses, but arterial pH fell only in
      ewes. Fetal body and brain weights were similar between groups. In three of eight
      EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum
      and cerebellum associated with focal cortical neuronal death and gliosis.
      Overall, there was no evidence of cystic lesions, inflammation, increased
      apoptosis, or white matter injury. We conclude that daily EtOH exposure during
      the third trimester-equivalent of ovine pregnancy has modest physiological
      effects on the fetus and no gross effects on fetal white matter development.

PMID- 21715700
TI  - Peripheral regulation of prolactin by oxytocin: focus on "Systemic oxytocin
      induces a prolactin secretory rhythm via the pelvic nerve in ovariectomized
      rats".

PMID- 21715701
TI  - Too salty for worms: hypertonic stress challenges proteostasis networks. Focus on
      "Hypertonic stress induces rapid and widespread protein damage in C. elegans".

PMID- 21715702
TI  - Preferential D2 or preferential D3 dopamine agonists in restless legs syndrome.
AB  - OBJECTIVE: A comparison between equivalent low doses of the D2 preferential
      agonist bromocriptine and the D3 preferential agonist pramipexole was performed
      in order to understand which dopamine agonist receptor subtype plays the main
      role in the treatment of restless legs syndrome (RLS) with periodic leg movements
      during sleep (PLMS). METHODS: A placebo-controlled, prospective, single-blind
      investigation was carried out on 45 drug-naive patients with idiopathic RLS. Each
      patient underwent 2 consecutive full night polysomnographic studies. The first
      night was performed without medication. Prior to the second night, one group
      received a single oral dose of 0.25 mg pramipexole while a second group received
      a single oral dose of 2.5 mg bromocriptine, and the remaining patients received
      placebo. Additionally, symptoms of restlessness were assessed. RESULTS:
      Subjective symptoms improved with both pramipexole and bromocriptine; however,
      the amelioration after pramipexole was scored higher. Only pramipexole induced an
      improvement in sleep efficiency and a reduction in wakefulness after sleep onset.
      Pramipexole was more effective than bromocriptine in reducing periodic leg
      movements, in particular in patients with a high baseline periodic leg movements
      index. Typical periodic leg movements, with an interval ranging between 10 and 40
      seconds, disappeared completely after pramipexole treatment but persisted, even
      if reduced, after bromocriptine. CONCLUSIONS: Dopamine agonists targeting the
      dopamine D3 receptor subtype have a higher efficacy on periodic leg movements and
      RLS than a drug that preferentially targets the D2 receptor subtype.
      CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for
      patients with RLS pramipexole as compared to an estimated equivalent dose of
      bromocriptine results in greater improvement in some measures of RLS and PLMS
      severity after one night of treatment.

PMID- 21715703
TI  - Symptomatic ICH and outcomes in patients after IV tPA: a business of risk or
      risky business?

PMID- 21715704
TI  - Comment: The increasing complexity of phenotype-genotype correlations in CMT.

PMID- 21715705
TI  - Late-onset lower motor neuronopathy: a new autosomal dominant disorder.
AB  - OBJECTIVE: Characterization of a new type of late-onset autosomal dominant lower
      motor neuron disease. METHODS: Patients from 2 families underwent detailed
      neurologic, electrophysiologic, muscle biopsy, and laboratory investigations. MRI
      of lower limbs was performed in selected patients. DNA samples from leukocytes
      were used for molecular genetic linkage studies. RESULTS: First symptoms were
      muscle cramps and fasciculations after age 25-30, followed by a slowly
      progressive proximal and distal weakness without overt atrophy during the first
      decades of symptoms. Nerve conduction velocities were within normal range and EMG
      showed widespread neurogenic alterations. Muscle biopsy revealed characteristic
      neurogenic findings: fiber type grouping and group atrophy. MRI showed diffuse
      fatty-degenerative changes, marked in medial gastrocnemius. CONCLUSION: Exactly
      the same clinical phenotype has not previously been described, and linkage
      studies showed exclusion of known chromosomal loci for hereditary motor
      neuropathies, suggesting the disease we report may represent a new disorder.

PMID- 21715706
TI  - Genetic associations with brain microbleeds: Systematic review and meta-analyses.
AB  - OBJECTIVE: We performed a systematic review and meta-analyses to assess the
      evidence for genetic associations with brain microbleeds (BMBs). METHODS: We
      sought all published studies of the association between any genetic polymorphism
      and BMBs studied in a total of >100 people. We critically appraised studies, and
      calculated pooled odds ratios (ORs) using the generic inverse variance fixed
      effects method. We used I2 and chi2 statistics to assess heterogeneity, and fail
      safe N estimates to assess the robustness of our results. RESULTS: Only the APOE
      epsilon2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351
      participants). Compared with people with the epsilon3/epsilon3 genotype, carriers
      of the epsilon4 allele (epsilon4+) were statistically significantly more likely
      to have BMBs in any location (epsilon4+ vs epsilon3/epsilon3: pooled OR 1.22, 95%
      confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this
      association appeared slightly stronger (epsilon4+ vs epsilon3/epsilon3: pooled OR
      1.35, 95% CI 1.10-1.66, p = 0.005). The association of epsilon4+ genotypes with
      strictly lobar BMBs was reasonably robust to potential publication and reporting
      biases. CONCLUSIONS: Given the known associations of APOE alleles with lobar
      intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support
      the concept that strictly lobar BMBs may be an imaging biomarker of cerebral
      amyloid angiopathy.

PMID- 21715707
TI  - Patient outcomes from symptomatic intracerebral hemorrhage after stroke
      thrombolysis.
AB  - OBJECTIVES: To assess the impact of symptomatic intracerebral hemorrhage (sICH)
      on outcome of thrombolysis-treated ischemic stroke patients, as additional to
      recognized prognosticators. METHODS: The study cohort included 985 ischemic
      stroke patients treated with IV thrombolysis at the Helsinki University Central
      Hospital (1995-2008). In a multivariable model adjusted for baseline stroke
      severity, age, onset-to-treatment time, baseline glucose, hyperdense cerebral
      artery sign, and early infarct signs on baseline imaging, and prior modified
      Rankin Scale (mRS), we calculated risk ratios (RRs) of patients with sICH
      (separately per Safe Implementation of Thrombolysis in Stroke[SITS]-Monitoring
      Study, European Cooperative Acute Stroke Study II [ECASS-II], and National
      Institute of Neurological Disorders and Stroke [NINDS] definitions) for poor 3
      month outcome (mRS 3-6) and mortality. Receiver operating characteristic (ROC)
      curve and integrated discrimination improvement (IDI) evaluated impact of sICH on
      outcome. Internal cross-validation of the model was done with bootstrap
      statistics. RESULTS: The frequency of sICH was 2.1% (SITS), 7.0% (ECASS-II), and
      9.4% (NINDS). RRs for poor and fatal outcome, respectively, were 1.7 and 4.8
      (SITS), 1.6 and 3.8 (ECASS-II), and 1.6 and 3.4 (NINDS). In IDI analyses, sICH
      improved prediction model for 3-month mRS of 3-6 and 4-6, respectively, by 1.4%
      and 3.0% (SITS), 4.0% and 5.9% (ECASS-II), and 4.7% and 6.1% (NINDS). In case of
      3-month mRS 5-6 and mortality, it was 6.1% and 5.3% (SITS), 11.3% and 9.3% (ECASS
      II), and 10.3% and 8.0% (NINDS). ROC analysis revealed similar results.
      CONCLUSIONS: Patients with sICH have increased risk of poor and fatal outcome.
      Compared with recognized stroke prognosticators, contribution of sICH is smaller.
      Definition-wise, ECASS-II- and NINDS-based sICH contribute relatively more; ECASS
      II has the largest contribution to worst outcomes.

PMID- 21715708
TI  - Non-5q spinal muscular atrophies: the alphanumeric soup thickens.

PMID- 21715709
TI  - Plasma Abeta and PET PiB binding are inversely related in mild cognitive
      impairment.
AB  - OBJECTIVE: To evaluate the relations between PET Pittsburgh compound B (PiB-PET)
      binding (amyloid imaging) and plasma Abeta in patients with mild cognitive
      impairment (MCI) and similarly aged controls. METHODS: In 20 patients with MCI
      and 19 cognitively intact controls (case-control study), PiB binding potential
      (BP(nd)) was assessed in 4 regions, and total brain excluding cerebellum,
      referenced to cerebellar binding. The mean of plasma Abeta levels measured in
      duplicate was analyzed. RESULTS: Plasma Abeta42/Abeta40 ratio was decreased in
      MCI compared to controls (mean 0.15 SD 0.04 vs mean 0.19 SD 0.07, p = 0.03) but
      Abeta40 (p = 0.3) and Abeta42 (p = 0.06) levels did not differ between the 2
      groups. PiB BP(nd) was increased in MCI compared to controls in the cingulate (p
      = 0.02), parietal (p = 0.02), and total brain (p = 0.03), but not in prefrontal
      cortex (p = 0.08) or parahippocampal gyrus (p = 0.07). Linear regression analyses
      adjusting for age, sex, and cognitive test scores showed that low Abeta42/Abeta40
      ratio was associated with high cingulate, parietal, and total brain PiB binding
      (0.01< p <= 0.05). These associations between PiB binding and the Abeta42/Abeta40
      ratio were strongest in PiB-positive subjects and within the MCI group.
      CONCLUSIONS: Though cross-sectional, the findings support the "sink" hypothesis
      that increased brain Abeta is accompanied by lower peripheral levels of Abeta,
      particularly the Abeta42/Abeta40 ratio in patients with MCI. The association
      between PiB binding and the plasma Abeta42/Abeta40 ratio suggests possible use of
      plasma Abeta combined with PiB binding as a risk biomarker with potential
      clinical application.

PMID- 21715710
TI  - Treating the chief complaint: hand rejuvenation for Hirayama disease.

PMID- 21715711
TI  - Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous
      mitofusin 2 mutations.
AB  - OBJECTIVE: Mutations in mitofusin 2 (MFN2) are the most common cause of axonal
      Charcot-Marie-Tooth disease (CMT2). Over 50 mutations have been reported, mainly
      causing autosomal dominant disease, though families with homozygous or compound
      heterozygous mutations have been described. We present 3 families with early
      onset CMT2 associated with compound heterozygous MFN2 mutations. Transcriptional
      analysis was performed to investigate the effects of the mutations. METHODS:
      Patients were examined clinically and electrophysiologically; parents were also
      examined where available. Genetic investigations included MFN2 DNA sequencing and
      dosage analysis by multiplex ligation-dependent probe amplification. MFN2 mRNA
      transcripts from blood lymphocytes were analyzed in 2 families. RESULTS: Compound
      heterozygosity for MFN2 mutations was associated with early-onset CMT2 of varying
      severity between pedigrees. Parents, where examined, were unaffected and were
      heterozygous for the expected mutations. Four novel mutations were detected (one
      missense, one nonsense, an intragenic deletion of exons 7 + 8, and a 3-base pair
      deletion), as well as 2 previously reported missense mutations. Transcriptional
      analysis demonstrated aberrant splicing of the exonic deletion and indicated
      nonsense-mediated decay of mutant alleles with premature truncating mutations.
      CONCLUSIONS: Our findings confirm that MFN2 mutations can cause early-onset CMT2
      with apparent recessive inheritance. Novel genetic findings include an intragenic
      MFN2 deletion and nonsense-mediated decay. Carrier parents were asymptomatic,
      suggesting that MFN2 null alleles can be nonpathogenic unless coinherited with
      another mutation.

PMID- 21715712
TI  - Favorable functional outcomes in acute ischemic stroke patients with subclinical
      hypothyroidism.
AB  - OBJECTIVE: To investigate the protective effects of subclinical hypothyroidism
      (SCH) on ischemic stroke severity and its functional outcome. METHODS: Seventy
      three consecutive patients admitted for first-ever cerebral ischemic stroke who
      met the inclusion criteria of this study were included. Serum thyroid-stimulating
      hormone (TSH) levels were measured for all patients. Stroke severity was recorded
      for each patient on admission using the NIH Stroke Scale. The patients were
      followed, and their functional outcomes were evaluated at 1 and 3 months after
      stroke using the modified Rankin Scale (mRS) and the Barthel Index. All values
      were compared between patients with and without SCH (serum TSH in the range of
      2.5-10 mIU/L, with normal thyroid function test results). RESULTS: Of the
      patients, 49 (67.1%) had normal serum TSH, and 24 (32.8%) had SCH. Patients with
      higher levels of serum TSH tended to have a milder stroke on admission with a
      significantly better outcome, described as a mRS score of 0 or 1, at 1 (p =
      0.029) and 3 (p = 0.048) months of follow-up. Mortality was also found to be
      lower in the group of patients with SCH (p = 0.008, at 3 months of follow-up).
      CONCLUSIONS: This study showed a significant protective association of SCH with
      better outcomes and lower mortality after cerebral ischemic stroke. Possible
      explanations for this association are ischemic preconditioning, reduced
      adrenergic tone, and hypometabolic state.

PMID- 21715713
TI  - Characterization and application of oviductal epithelial cells in vitro in Gallus
      domesticus.
AB  - Chicken oviductal epithelium produces large quantities of egg white protein in
      daily cycles. In this study, we cultured and characterized oviductal epithelial
      cells (OECs) from juvenile (10-wk-old) chickens and from actively laying (30-wk
      old) hens. The juvenile OECs were maintained over passage 25 and were positive
      for toluidine blue, lectin-ConA, HPA, UEA-1, WFA, WGA, anti-OVA, anti-ESR1, and
      anti-PGR, whereas the adult OECs were cultured over passage 6 and were positive
      for toluidine blue, periodic acid-Schiff, lectin-ConA, WFA, WGA, anti-OVA, anti
      ESR1, and anti-PGR. To investigate the optimal concentration of steroid hormones
      for inducing egg white protein genes in vitro, we examined the effects of
      estrogen, diethylstilbestrol, progesterone, and corticosterone on OECs. Results
      showed that oviduct-specific levels of avidin, ovalbumin, ovomucin, lysozyme,
      ESR1, and PGR gene expression were significantly elevated in steroid hormone
      treated OECs compared with those of untreated cells (P < 0.05). Ovalbumin protein
      was also secreted into culture medium from hormone-treated OECs. In addition, to
      examine the application of OECs for avian transgenesis, we introduced human
      thrombopoietin (THPO)-expressing lentiviral vector controlled by a 3.5-kb
      ovalbumin promoter into cultured OECs, and THPO expression was significantly
      induced with diethylstilbestrol or progesterone in juvenile OECs (P < 0.05) and
      in adult OECs (P < 0.05). In conclusion, these data demonstrate the potential of
      cultured OECs as a model system for providing a better understanding of the
      regulation of gene expression and for the production of an avian transgenic
      bioreactor.

PMID- 21715714
TI  - A structural view of egg coat architecture and function in fertilization.
AB  - Species-restricted interaction between gametes at the beginning of fertilization
      is mediated by the extracellular coat of the egg, a matrix of cross-linked
      glycoprotein filaments called the zona pellucida (ZP) in mammals and the
      vitelline envelope in nonmammals. All egg coat subunits contain a conserved
      protein-protein interaction module-the "ZP domain"-that allows them to polymerize
      upon dissociation of a C-terminal propeptide containing an external hydrophobic
      patch (EHP). Recently, the first crystal structures of a ZP domain protein, sperm
      receptor ZP subunit zona pellucida glycoprotein 3 (ZP3), have been reported,
      giving a glimpse of the structural organization of the ZP at the atomic level and
      the molecular basis of gamete recognition in vertebrates. The ZP module is
      divided in two related immunoglobulin-like domains, ZP-N and ZP-C, that contain
      characteristic disulfide bond patterns and, in the case of ZP-C, also incorporate
      the EHP. This segment lies at the interface between the two domains, which are
      connected by a long loop carrying a conserved O-glycan important for binding to
      sperm in vitro. The structures explain several apparently contradictory
      observations by reconciling the variable disulfide bond patterns found in
      different homologues of ZP3 as well as the multiple ZP3 determinants
      alternatively involved in gamete interaction. These findings have implications
      for our understanding of ZP subunit biogenesis; egg coat assembly, architecture,
      and interaction with sperm; structural rearrangements leading to
      postfertilization hardening of the ZP and the block to sperm binding; and the
      evolutionary origin of egg coats.

PMID- 21715715
TI  - Determination of Fsh quantity and bioactivity during sex differentiation and
      oogenesis in European sea bass.
AB  - Follicle-stimulating hormone (FSH) is a glycoprotein hormone that plays a key
      role in the regulation of gonadal functions in vertebrates. The present study
      reports the monitoring of pituitary and plasma Fsh levels during sex
      differentiation and oogenesis in European sea bass (Dicentrarchus labrax) using a
      homologous immunoassay and an in vitro bioassay. Both assays were used
      complementarily for the first time in a fish species. High levels of Fsh
      bioactivity in plasma were found during the initial phases of sexual
      differentiation. Plasma and pituitary Fsh (quantity and bioactivity) levels and
      biological to immunological (B:I) ratios were higher in females than in males,
      suggesting sexual dimorphism in the synthesis and potency of Fsh. In females, the
      B:I ratios in adult were lower than during sex differentiation indicating that
      Fsh would be less biopotent in the adult stage. Plasma Fsh bioactivity levels
      increased during vitellogenesis, suggesting that Fsh would be involved in the
      regulation of the midphases of oogenesis, whereas luteinizing hormone would be
      responsible for the final events.

PMID- 21715717
TI  - Bleeding in acute coronary syndromes and percutaneous coronary interventions:
      position paper by the Working Group on Thrombosis of the European Society of
      Cardiology.
AB  - Bleeding has recently emerged as an important outcome in the management of acute
      coronary syndromes (ACS), which is relatively frequent compared with ischaemic
      outcomes and has important implications in terms of prognosis, outcomes, and
      costs. In particular, there is evidence that patients experiencing major bleeding
      in the acute phase are at higher risk for death in the following months, although
      the causal nature of this relation is still debated. This position paper aims to
      summarize current knowledge regarding the epidemiology of bleeding in ACS and
      percutaneous coronary intervention, including measurement and definitions of
      bleeding, with emphasis on the recent consensus Bleeding Academic Research
      Consortium (BARC) definitions. It also provides an European perspective on
      management strategies to minimize the rate, extent, and consequences of bleeding.
      Finally, the research implications of bleeding (measuring and reporting bleeding
      in trials, the importance of bleeding as an outcome measure, and bleeding as a
      subject for future research) are also discussed.

PMID- 21715716
TI  - Loss of SPEF2 function in mice results in spermatogenesis defects and primary
      ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) results from defects in motile cilia function.
      Mice homozygous for the mutation big giant head (bgh) have several abnormalities
      commonly associated with PCD, including hydrocephalus, male infertility, and
      sinusitis. In the present study, we use a variety of histopathological and cell
      biological techniques to characterize the bgh phenotype, and we identify the bgh
      mutation using a positional cloning approach. Histopathological,
      immunofluorescence, and electron microscopic analyses demonstrate that the male
      infertility results from shortened flagella and disorganized axonemal and
      accessory structures in elongating spermatids and mature sperm. In addition,
      there is a reduced number of elongating spermatids during spermatogenesis and
      mature sperm in the epididymis. Histological analyses show that the hydrocephalus
      is characterized by severe dilatation of the lateral ventricles and that bgh
      sinuses have an accumulation of mucus infiltrated by neutrophils. In contrast to
      the sperm phenotype, electron microscopy demonstrates that mutant respiratory
      epithelial cilia are ultrastructurally normal, but video microscopic analysis
      shows that their beat frequency is lower than that of wild-type cilia. Through a
      positional cloning approach, we identified two sequence variants in the gene
      encoding sperm flagellar protein 2 (SPEF2), which has been postulated to play an
      important role in spermatogenesis and flagellar assembly. A causative nonsense
      mutation was validated by Western blot analysis, strongly suggesting that the bgh
      phenotype results from the loss of SPEF2 function. Taken together, the data in
      this study demonstrate that SPEF2 is required for cilia function and identify a
      new genetic cause of PCD in mice.

PMID- 21715720
TI  - The fifth "C" is cost: highlights from ASCO 2011.

PMID- 21715721
TI  - Will risk evaluation and mitigation strategies ever be accepted?

PMID- 21715722
TI  - Does use of the adjuvant! model influence use of adjuvant therapy through better
      risk communication?
AB  - Adjuvant! is a model that provides recurrence and mortality risk predictions for
      patients with breast cancer considering adjuvant therapies. Although low-risk
      patients who saw Adjuvant! chose adjuvant therapy less frequently, whether this
      was because of educational or other aspects of the decision aid is unknown. The
      authors explored whether Adjuvant! affects choice of therapy through increased
      patient knowledge. A subset of data were analyzed from a cluster randomized trial
      in which oncology practices in 2 major United States cities were randomly
      assigned to use either Adjuvant! or an informational pamphlet to educate
      patients. Of 405 patients, 48 were low-risk, with 28 assigned to the decision aid
      and 20 to the pamphlet. Among the low-risk patients, using frequency tables and
      Fisher exact tests, the authors explored whether Adjuvant! was associated with
      more accurate patient estimates of survival; whether accuracy was associated with
      treatment choice; and whether, after controlling for accuracy, any remaining
      association was seen between Adjuvant! and treatment choice. Adjuvant! was
      associated with more accurate estimates of baseline prognosis compared with the
      pamphlet (57% vs. 25%; P = .04). Patients who had more accurate estimates of
      baseline prognosis were less likely to choose adjuvant therapy (62% vs. 89%; P =
      .04). After controlling for accuracy, no statistically significant association
      was found between the use of Adjuvant! and adjuvant therapy (P = .59 and P = .11
      for inaccurate and accurate patients, respectively). Adjuvant! seems to influence
      patient choice through educational rather than other means of persuasion.
      However, many patients held inaccurate risk perceptions after viewing Adjuvant!.

PMID- 21715724
TI  - Heparin-induced thrombocytopenia in cancer.
AB  - Heparin-induced thrombocytopenia is a common and clinically important drug
      induced complication that can cause life- and limbthreatening thrombosis.
      Epidemiologically, the disease has been studied in many different clinical
      settings, but little is known about it in cancer patients, a population at
      increased risk for thrombosis and thus exposure to heparin products.
      Additionally, thrombocytopenia is a common finding in cancer patients. The
      convergence of these variables highlights the importance of an increased
      understanding of the disease in cancer patients.

PMID- 21715725
TI  - Risk assessment and prophylaxis for VTE in cancer patients.
AB  - The frequency of venous thromboembolism (VTE) is rising in patients with cancer.
      VTE contributes to mortality and morbidity, but the risk for VTE can vary widely
      between individual patients. Clinical risk factors for VTE in cancer include
      primary site of cancer, use of systemic therapy, surgery, and hospitalization.
      Biomarkers predictive of VTE include platelet and leukocyte counts, hemoglobin, D
      dimer, and tissue factor. A recently validated risk model incorporates 5 easily
      available variables and can be used clinically to identify patients at increased
      risk of VTE. In high-risk settings, including surgery and hospitalization,
      thromboprophylaxis with either unfractionated heparin or low-molecular-weight
      heparins has been shown to be safe and effective. Recent studies have also
      suggested a potential benefit for thromboprophylaxis in the ambulatory setting,
      although criteria for selecting patients for prophylaxis are not currently well
      defined. This article focuses on recent and ongoing studies of risk assessment
      and prophylaxis in patients with cancer.

PMID- 21715726
TI  - Risk stratification for acute pulmonary embolism.
AB  - This article discusses state-of-the-art techniques for predicting risk of death
      after acute pulmonary embolism (PE), with special attention to how underlying
      malignancy adversely affects survival after an episode. Current methods of risk
      stratification generally categorize patients with PE as low-, moderate-, and high
      risk for in-hospital adverse outcomes of respiratory failure, circulatory shock,
      and death. Published risk stratification studies find that patients with PE and
      an underlying malignancy have a worse prognosis, but no validated risk
      stratification criteria have been published specifically for these patients.
      Standard treatment is full-dose heparin followed by oral anticoagulation. The
      term escalated treatment refers to the use of systemic or intrapulmonary
      fibrinolytic agents, catheter-based treatment, or surgical embolectomy. Most
      patients with low-risk PE (normal vital signs and normal serum troponin, brain
      natriuretic peptide, and normal echocardiography) are treated successfully with
      standard anticoagulation, and many can be treated as outpatients. In contrast,
      patients with high-risk PE (systolic blood pressure < 90 mm Hg and no
      contraindications) often benefit from escalated treatment. Treatment decisions
      for patients with moderate-risk PE (normotension with evidence of right
      ventricular damage or dysfunction) are most controversial. Most patients in this
      category of risk recover with standard therapy, but some benefit from escalated
      treatment. Patients with cancer with an incidentally discovered PE should be risk
      stratified the same as those who have clinically suspected PE.

PMID- 21715727
TI  - Preliminary study on the galectin molecular diversity in Moroccoan Phlebotomus
      papatasi sandfly population.
AB  - CONTEXT: Galactose binding protein (PpGalec) plays an important role in the
      specificity of Phlebotomus papatasi sandfly for Leishmania major. The molecular
      diversity of this ligand is currently unknown but might have some influence on
      the ability of PpGalec to efficiently recognize L. major in natural sandfly
      populations. OBJECTIVE: To explore the molecular diversity of the P. papatasi
      Galectin gene (PpGalec) in natural sandfly population of Morocco. RESULTS &
      CONCLUSIONS: Sequence variations of PpGalec was analyzed in 31 P. papatasi
      specimens collected from endemic and non-endemic zoonotic cutaneous leishmaniasis
      foci of Morocco. Among the 211 amino acid positions analyzed, 11 are subjected to
      mutation. Interestingly, we observe that one mutation directly affect an amino
      acid known to be involved in the substrate recognition by galectin. The
      repercussion of this polymorphism on the capacity of the galectin to efficiently
      bind the L. major Lipophosphoglycane (LPG) awaits further investigations.

PMID- 21715723
TI  - Venous thromboembolic disease.

PMID- 21715728
TI  - Functional responses of Laccotrephes griseus (Hemiptera: Nepidae) against Culex
      quinquefasciatus (Diptera: Culicidae) in laboratory bioassay.
AB  - BACKGROUND AND OBJECTIVES: In integrated vector management programmes, major
      emphasis is given on the application of biocontrol agents. In the present study,
      the hemipteran water bug, Laccotrephes griseus (Hemiptera: Nepidae) was evaluated
      to establish its functional response against the immature Culex quinquefasciatus
      Say in the laboratory. METHODS: Adult water bugs (L. griseus) were collected from
      different ponds in Bankura, West Bengal, India. Predation rate was determined in
      semi-field conditions. Functional response, regression equation analysis and rate
      of predation were also determined in the presence of an alternative prey.
      RESULTS: The long-term predation experiment (up to 30 days) revealed that L.
      griseus is a very good predator of mosquito larvae. The functional curve analysis
      of L. griseus exhibited a Type II functional response. Their handling times and
      coefficient of attack rates were 29.37 min and 2.17 respectively. Regression
      equations showed that consumption rate was directly proportional to prey and
      predator densities and inversely proportional to the search area. The selectivity
      index, niche width and food breadth were also determined. INTERPRETATION AND
      CONCLUSION: The present study revealed that L. griseus can consume a good number
      of mosquito larvae in the laboratory conditions. The long-term bioassay also
      indicates their predatory response against mosquito larvae in the semi-field
      conditions. The result of selectivity index, niche width and food breadth were
      also highest for Cx. quinquefasciatus. In these respects, the water bugs L.
      griseus are indicative of their release in the aquatic habitat where Cx.
      quinquefasciatus is the most dominant mosquito species.

PMID- 21715729
TI  - Prevalence of endemic Bancroftian filariasis in the high altitude region of south
      eastern Nigeria.
AB  - BACKGROUND & OBJECTIVES: The study was aimed at determining the prevalence and
      intensity of Wuchereria bancrofti microfilaraemia in a high altitude region of
      south-eastern Nigeria, and ascertaining the prevalence of clinical signs and
      symptoms associated with the filarial infections. METHODS: Thick smear of 50 MUl
      finger-prick blood collected at night between 2200 and 0200 hrs from consenting
      persons were stained with Giemsa and examined microscopically in a cross
      sectional study. Consenting individuals were examined for various gradations of
      hydrocele, limb and scrotal elephantiasis by qualified medical personnel.
      RESULTS: The prevalence of W. bancrofti microfilaraemia was 4.3%, highest in the
      older people but comparable in both sexes. The overall micro filarial (mf)
      geometric mean intensity (GMI) among mf positive individuals was 123 mf/ml of
      blood (138 mf/ml for males and 110 mf/ml of blood for females); and rose
      significantly with increasing age (one-way analysis of variance; p <0.001).
      Prevalence of clinical manifestations was: hydrocele (7.1%), scrotal
      elephantiasis (4%), and limb elephantiasis (6%). The mf GMI was significantly
      higher among those without hydrocele or limb elephantiasis than among those with
      the clinical manifestations (t-test; p <0.05 for both tests); the opposite was
      the case for scrotal elephantiasis, (t-test; p <0.01). CONCLUSION: Filariasis is
      endemic in the high altitude region of south-eastern Nigeria. The chronic
      clinical manifestations observed there underscore the need for urgent combination
      therapy interventions.

PMID- 21715730
TI  - Environmental factors associated with larval habitats of anopheline mosquitoes
      (Diptera: Culicidae) in irrigation and major drainage areas in the middle course
      of the Rift Valley, central Ethiopia.
AB  - BACKGROUND & OBJECTIVES: Larval control is an integral part of malaria vector
      management in Ethiopia and elsewhere. For effective larval control, a sound
      understanding of the factors responsible for spatio-temporal variation in larval
      production is essential. A study was thus conducted to characterize larval
      habitats of anopheline mosquitoes in irrigation and major drainage areas between
      Adami Tulu and Meki towns, in the middle course of the Ethiopian Rift Valley.
      METHODS: Aquatic habitats were sampled for anopheline larvae and the associated
      environmental variables (water temperature, turbidity, water current, water pH
      and other variables) were measured, characterized and analyzed. RESULTS:
      Microscopic identification of the late instars (III and IV) of anopheline larvae
      collected throughout the study period yielded nearly 47.6% Anopheles pharoensis,
      32.1% An. arabiensis, 17.1% An. squamosus and only 3.2% of other species (An.
      coustani and An. cinereus). Larvae of the local malaria vectors, An. arabiensis
      and An. pharoensis were most abundantly sampled from sand pools and natural
      swamps, respectively. Logistic regression analysis detected four best predictor
      variables associated with larval abundance of malaria vector species. Thus,
      relative abundance of An. arabiensis larvae was significantly and inversely
      associated with aquatic vegetation and water current, whereas the relative
      abundance of An. pharoensis larvae was significantly and positively associated
      with water temperature and the presence of algae in the water bodies. CONCLUSION:
      Dry season anopheline larval habitats such as riverine sand pools that are
      created and maintained by perennial water bodies and their associated water
      development projects need to be considered in vector control operations.

PMID- 21715731
TI  - Storage time effect on blood diet for tsetse mass production in sterile insect
      technique.
AB  - BACKGROUND & OBJECTIVES: Different methods have been developed for tsetse and
      trypanosomiasis control or eradication but all these have their specific
      advantages and limitations. However, a combination of methods could be used as
      part of an Area-wide Integrated Pest Management (AWPM). The sterile insect
      technique (SIT) as a technique of choice for eradication of tsetse flies requires
      mass production of flies in the laboratories. Since tsetse's are exclusively
      haemotophogous insects, a quality blood diet is needed for maintenance of flies
      with optimum production. The aim of this study was to establish the optimum
      storage time of blood diet for tsetse colonies. METHODS: A total of 450 flies
      Glossina austeni were fed on different batches of blood (collected in 2004, 2005,
      2006, 2007 and 2008) three times a week. Pupae were collected daily and mortality
      checks were done on weekly basis. The quality of the blood diet was measured by
      observation of tsetse production parameters including survival, pupae production
      and size. RESULTS: The survival of flies fed on 2004 and 2006 batches had lower
      survival compared to the rest of the batches. Also the 2005 batch had a
      significant higher number of pupae compared to the production in other
      treatments. The 2004 and 2005 batches had more of small pupae (class A & B)
      compared to the other batches. INTERPRETATION & CONCLUSION: There was a
      significant difference between the blood batches and the production parameters
      were better in the last three years, i.e. 2008, 2007 and 2006. Therefore, this
      study recommends three years to be an optimum storage time for blood diet under
      regional conditions. Also the storage temperature conditions should remain stable
      at -20oC.

PMID- 21715732
TI  - Antagonistic antimalarial properties of pawpaw leaf aqueous extract in
      combination with artesunic acid in Plasmodium berghei-infected mice.
AB  - BACKGROUND & OBJECTIVES: Artemisinins, the main stay in the treatment of malaria
      are used in combinations with other antimalarials to forestall resistance, as
      artemisinin-combination therapies (ACTs). However, ACTs are expensive and some of
      the non-artemisinin components are not well-tolerated by patients. There are
      several folkloric and scientific proofs of the efficacy of herbal remedies for
      malaria. Mature leaves of Carica papaya is widely used to treat malaria in
      several African countries. An ACT involving a medicinal herb extract or its
      active constituent(s) will provide an indigenous alternative/herbal ACT. METHODS:
      Mature fresh leaves of Carica papaya were grounded and macerated in cold
      distilled water for 24 h and the extract (PCE) was stored in the refrigerator for
      seven days. Fresh extracts were made as needed. The antiplasmodial activity of
      PCE and/or artesunic acid were determined by using the Peter's 4-day suppressive
      test in Plasmodium berghei-infected mice. The ED50 and ED90 were calculated from
      the dose-response relationships. RESULTS: The combination of 50 mg/kg of PCE and
      15 mg/kg of artesunic acid produced a significant reduction of parasitemia
      (81.25%), compared to 50 mg/kg PCE alone (37.7%). The mean survival time of the
      combinations of PCE and 15 mg/kg of artesunic acid, and PCE alone followed a dose
      dependent manner. The ED50 of PCE showed that it has a very good activity. The
      isobolar equivalent (IE) calculated from the ED90 of PCE in combination with
      artesunic acid showed that the interaction was antagonistic. INTERPRETATION &
      CONCLUSION: Although pawpaw alone was found to have a very good activity, its
      combination with artesunic acid is antagonistic. Combinations of artemisinins and
      pawpaw show little promise for combination therapy development.

PMID- 21715733
TI  - A study on coverage, compliance and awareness about mass drug administration for
      elimination of lymphatic filariasis in a district of West Bengal, India.

PMID- 21715734
TI  - Mass-treatment and insecticide-spraying of animal reservoirs for emergency
      control of Rhodesiense sleeping sickness in Uganda.

PMID- 21715735
TI  - Insecticide susceptibility profile of the principal malaria vector, Anopheles
      gambiae s.l. (Diptera: Culicidae), in north-central Nigeria.

PMID- 21715736
TI  - Mosquitocidal activity of some volatile oils against Aedes caspius mosquitoes.

PMID- 21715737
TI  - Susceptibility status of dengue vectors against various insecticides in Koderma
      (Jharkhand), India.

PMID- 21715738
TI  - Genital filariasis masquerading as testicular torsio.

PMID- 21715739
TI  - Trypanosomiasis in an infant from India.

PMID- 21715740
TI  - Ion beam sputtering induced nanostructuring of polycrystalline metal films.
AB  - The development of fine scale nanostructures in polycrystalline metal films by
      off-normal ion beam sputtering (IBS) follows similar mechanisms to those in
      random targets, i.e. the pattern results from the interplay of curvature
      dependent-roughening and various smoothing processes. By grazing angle IBS of the
      deposited metal films it is possible to fabricate metallic nanoripples,
      nanowires, and nanorods onto semiconductor or insulator substrates without using
      a template. It has been found that the rms roughness of the as-deposited film is
      substantially reduced under ion bombardment before the development of nanoscale
      patterns. The structural anisotropy of the sputtered morphology can have a great
      influence on the local physical properties of the underlying material. In this
      paper, we shall review the experimental results on the formation and
      characteristics of the IBS ripples on polycrystalline metal films prepared by the
      physical vapor deposition (PVD) technique.

PMID- 21715741
TI  - Ion erosion induced nanogrooves: temporal evolution and azimuth dependence.
AB  - Ion sputtering at grazing incidence of the Cu(001) surface leads to the formation
      of a regular pattern of nanogrooves with a well defined separation distance
      between the grooves. The grooves are only two atomic layers deep for a low ion
      flux and their height remains the same independent of sputter time. The average
      separation distance of the nanogrooves is at least 5 nm and can be increased
      beyond 40 nm, depending on substrate temperature, fluence, the ion's mass and
      energy. Anneal experiments of a nanogroove pattern also show an increase in
      average nanogroove separation with anneal time. The increase of the average
      nanogroove separation with time is larger for nanogrooves created along a ?100?
      azimuth compared to the ?110? azimuth. The ?100? oriented step edges show a high
      density of kinks, suggesting that detachment from kinks is the rate limiting step
      in the process that governs the periodicity. Also both adatoms and vacancies are
      involved in this process, while the grazing incident ion beam continuously
      creates new nanogrooves. The creation of new nanogrooves and the movement
      observed during annealing are used as ingredients for a description of the
      temporal behaviour of the average nanogroove periodicity.

PMID- 21715742
TI  - Highly ordered nanopatterns on Ge and Si surfaces by ion beam sputtering.
AB  - The bombardment of surfaces with low-energy ion beams leads to material erosion
      and can be accompanied by changes in the topography. Under certain conditions
      this surface erosion can result in well-ordered nanostructures. Here an overview
      of the pattern formation on Si and Ge surfaces under low-energy ion beam erosion
      at room temperature will be given. In particular, the formation of ripple and dot
      patterns, and the influence of different process parameters on their formation,
      ordering, shape and type will be discussed. Furthermore, the internal ion beam
      parameters inherent to broad beam ion sources are considered as an additional
      degree of freedom for controlling the pattern formation process. In this context:
      (i) formation of ripples at near-normal ion incidence, (ii) formation of dots at
      oblique ion incidence without sample rotation, (iii) transition between patterns,
      (iv) formation of ripples with different orientations and (v) long range ordered
      dot patterns will be presented and discussed.

PMID- 21715743
TI  - Ripple formation on silicon by medium energy ion bombardment.
AB  - The formation of a self-organized nanoscale ripple pattern after off-normally
      incident ion bombardment on the surface of amorphous materials, or on
      semiconductors like silicon that are easily amorphized by ion bombardment, has
      attracted much attention in recent years from the point of view of both theory
      and applications. As the energy of the impinging ions increases from low to
      medium, i.e. several hundred eV to a few tens of keV, the ratio of amplitude to
      wavelength of the generated ripple pattern becomes so large that inter-peak
      shadowing of the incident ion flux takes place. Morphologically, the sinusoidal
      surface profile starts to become distorted after prolonged ion bombardment under
      such conditions. Structural and compositional modifications of the ripple
      morphology generated under shadowing conditions include the formation of a
      thicker amorphous layer with high incorporation of argon atoms in the form of
      nanometer sized bubbles around the middle part of the front slope of the ripple
      facing the ion beam, as compared to the rear slope. The present paper reviews
      recent developments in the experimental study of morphological, structural and
      compositional aspects of ripple patterns generated on a silicon surface after
      medium keV (30-120 keV) argon bombardment mainly at an angle of ion incidence of
      60 degrees .

PMID- 21715744
TI  - Ripple formation and smoothening on insulating surfaces.
AB  - Ion bombardment of insulating surfaces such as Al(2)O(3) and SiO(2) produces
      ordered patterns of ripples. The ripple wavelength varies with ion energy,
      incidence angle and substrate temperature. A region of stability is also known to
      exist for near-normal incidence during Ar(+) ion bombardment, where initially
      rough surfaces are smoothened. A number of relaxation mechanisms are found to be
      operative under specific conditions, including: surface-confined viscous flow,
      impact-induced lateral currents and impact-assisted surface diffusion during ion
      bombardment at high temperatures. Most of the experimentally observed phenomena
      are explained through extension of the Bradley-Harper theory by the addition of
      these new processes. Phenomena that are not explained by the linear theory, such
      as the saturation of surface amplitude during the formation of ripples, are
      thought to arise from nonlinear effects. This contribution describes the present
      status of the linear theory relevant to this class of materials and recent
      experimental results.

PMID- 21715745
TI  - Synchrotron x-ray scattering from metal surfaces nanostructured by IBS.
AB  - Ion beam sputtering (IBS) can induce the formation of ordered nanostructures,
      whose properties depend on ion flux, sputtering angle, sample temperature, sample
      structure, surface symmetry, etc. For the comprehension of the time evolution of
      the formed nanostructure morphology it is necessary to perform in situ real time
      studies. In this review we shall describe results obtained using x-ray based
      techniques at synchrotron facilities to study in situ the time and temperature
      evolution of metal surfaces nanopatterned by ion sputtering. Different
      techniques, such as x-ray reflectivity, grazing incidence small angle x-ray
      scattering and x-ray surface diffraction have been used, each of them providing
      complementary information for the determination of the surface structure and
      morphology. In this review, we present some experiments done in recent years to
      show how these methods contributed to our understanding of the IBS process on
      metal surfaces.

PMID- 21715746
TI  - Ion-induced nanopatterns on semiconductor surfaces investigated by grazing
      incidence x-ray scattering techniques.
AB  - In this review we cover and describe the application of grazing incidence x-ray
      scattering techniques to study and characterize nanopattern formation on
      semiconductor surfaces by ion beam erosion under various conditions. It is
      demonstrated that x-rays under grazing incidence are especially well suited to
      characterize (sub)surface structures on the nanoscale with high spatial and
      statistical accuracy. The corresponding theory and data evaluation is described
      in the distorted wave Born approximation. Both ex situ and in situ studies are
      presented, performed with the use of a specially designed sputtering chamber
      which allows us to follow the temporal evolution of the nanostructure formation.
      Corresponding results show a general stabilization of the ordering wavelength and
      the extension of the ordering as a function of the ion energy and fluence as
      predicted by theory. The in situ measurements are especially suited to study the
      early stages of pattern formation, which in some cases reveal a transition from
      dot to ripple formation. For the case of medium energy ions crystalline ripples
      are formed buried under a semi-amorphous thick layer with a ripple structure at
      the surface being conformal with the crystalline/amorphous interface. Here, the x
      ray techniques are especially advantageous since they are non-destructive and
      bulk-sensitive by their very nature. In addition, the GI x-ray techniques
      described in this review are a unique tool to study the evolving strain, a topic
      which remains to be explored both experimentally and theoretically.

PMID- 21715747
TI  - Production of nanohole/nanodot patterns on Si(001) by ion beam sputtering with
      simultaneous metal incorporation.
AB  - We have established the conditions for which nanohole and nanodot patterns are
      produced on Si(001) surfaces by 1 keV Ar(+) ion beam sputtering (IBS) at normal
      incidence with an alternating cold cathode ion source (ACC-IS). Nanohole patterns
      are produced within a narrow IBS window for low ion fluxes (<100 uA cm(-2)) and
      relatively low ion fluences (<10(18) ions cm(-2)) whereas nanodot morphologies
      are produced above this window. The nanohole pattern is not stable after
      prolonged irradiation since it evolves to a nanodot morphology. Rutherford
      backscattering spectrometry (RBS) measurements show that nanohole patterns are
      produced when the metal content on the irradiated surfaces is higher (within (2.5
      3.5 * 10(15)) atoms cm(-2)) than in the case of nanodots (<2.5 * 10(15) atoms cm(
      2)). The different metal content is related to the ACC-IS operation, since the
      set-up provides simultaneous incorporation of Fe and Mo on the target surface
      from the erosion of the cathodes and sample holder, respectively. The role of
      metal incorporation on pattern selectivity has been corroborated qualitatively by
      extending the results obtained with the ACC-IS to a standard Kaufman-type source.
      In order to gain further information on the metal effects, chemical analysis of
      the surface has been performed to complement the compositional RBS results,
      showing for the first time the relevant participation of metal silicides. Further
      outlook and a discussion regarding the role of metal incorporation are also
      given.

PMID- 21715748
TI  - Linear stability and instability patterns in ion-sputtered silicon.
AB  - We study the patterns formed on Ar(+) ion-sputtered Si surfaces at room
      temperature as a function of the control parameters ion energy and incidence
      angle. We observe the sensitivity of pattern formation to artifacts such as
      surface contamination and report the procedures we developed to control them. We
      identify regions in control parameter space where holes, parallel mode ripples
      and perpendicular mode ripples form, and identify a region where the flat surface
      is stable. In the vicinity of the boundaries between the stable and pattern
      forming regions, called bifurcations, we follow the time dependence from
      exponential amplification to saturation and examine the amplification rate and
      the wavelength in the exponential amplification regime. The resulting power laws
      are consistent with the theory of nonequilibrium pattern formation for a type I
      (constant wavelength) bifurcation at low angles and for a type II (diverging
      wavelength) bifurcation at high angles. We discuss the failure of all sputter
      rippling models to adequately describe these aspects of the simplest experimental
      system studied, consisting of an elemental, isotropic amorphous surface in the
      simplest evolution regime of linear stability.

PMID- 21715749
TI  - Nanopatterning by multiple-ion-beam sputtering.
AB  - We conducted a systematic study on nanopatterning by multiple-ion-beam
      sputtering, focusing on the superposition of the simple patterns formed by
      individual ion beams. When Au(001) is simultaneously sputtered by two ion beams
      at grazing incidence, both nanodot and nanohole patterns are obtained. If a
      rippled surface is subsequently sputtered at normal incidence, a nanobead pattern
      is obtained. All of the obtained patterns consist of the nanopatterns formed by
      individual ion beams; however, the superposition of nanopatterns is not realized
      in its ideal form. We also discuss the microscopic mechanism of pattern formation
      by multiple-ion-beam sputtering, and consider the questions and possibilities
      remaining to be explored.

PMID- 21715750
TI  - Surface nanostructures by single highly charged ions.
AB  - It has recently been demonstrated that the impact of individual, slow but highly
      charged ions on various surfaces can induce surface modifications with nanometer
      dimensions. Generally, the size of these surface modifications (blisters,
      hillocks, craters or pits) increases dramatically with the potential energy of
      the highly charged ion, while the kinetic energy of the projectile ions seems to
      be of little importance. This paper presents the currently available experimental
      evidence and theoretical models and discusses the circumstances and conditions
      under which nanosized features on different surfaces due to the impact of slow
      highly charged ions can be produced.

PMID- 21715751
TI  - Dual-beam focused ion beam/electron microscopy processing and metrology of
      redeposition during ion-surface 3D interactions, from micromachining to self
      organized picostructures.
AB  - Focused ion beam (FIB) tools have become a mainstay for processing and metrology
      of small structures. In order to expand the understanding of an ion impinging a
      surface (Sigmund sputtering theory) to our processing of small structures, the
      significance of 3D boundary conditions must be realized. We consider ion erosion
      for patterning/lithography, and optimize yields using the angle of incidence and
      chemical enhancement, but we find that the critical 3D parameters are aspect
      ratio and redeposition. We consider focused ion beam sputtering for
      micromachining small holes through membranes, but we find that the critical 3D
      considerations are implantation and redeposition. We consider ion beam self
      assembly of nanostructures, but we find that control of the redeposition by ion
      and/or electron beams enables the growth of nanostructures and picostructures.

PMID- 21715752
TI  - Ion beam sputtering nanopatterning of thin metal films: the synergism of kinetic
      self-organization and coarsening.
AB  - Creation of self-organized surface nanostructures by ion beam sputtering (IBS)
      has strong potential for use in a broad range of technologies, from
      nanoelectronics and photonics to sensing and catalysis. Recently, we have
      developed a simple two-stage process for fabricating self-assembled arrays of Cu
      dots and lines on Si and SiO(2) substrates employing IBS of thin Cu films. We
      found that the self-assembled structures on the substrate result from a complex
      interaction between the structure-forming kinetic instability and various
      outcomes of the surface diffusion and coarsening, which tend to drive the surface
      pattern towards a thermodynamic equilibrium. Here, we analyze in detail the
      interplay of the kinetic nanopatterning and coarsening, in order to better
      understand the mechanisms defining the IBS-generated metallic structures on
      substrates of a different material. By means of kinetic Monte Carlo (KMC)
      modeling we investigate the pertinent trends of the self-organization at the
      surface of a metallic film. In the light of this discussion, we review the
      fabricated nanostructures. Finally, we present a KMC model of the two-stage IBS
      process and analyze the stability of the fabricated metal patterns at the surface
      of a substrate. We discuss the opportunities and challenges of this technique,
      concluding that the IBS creation of surface heterostructures provides
      considerable room for future numerical and experimental studies.

PMID- 21715753
TI  - Simulating discrete models of pattern formation by ion beam sputtering.
AB  - A class of simple, (2+1)-dimensional, discrete models is reviewed, which allow us
      to study the evolution of surface patterns on solid substrates during ion beam
      sputtering (IBS). The models are based on the same assumptions about the erosion
      process as the existing continuum theories. Several distinct physical mechanisms
      of surface diffusion are added, which allow us to study the interplay of erosion
      driven and diffusion-driven pattern formation. We present results from our own
      work on evolution scenarios of ripple patterns, especially for longer timescales,
      where nonlinear effects become important. Furthermore we review kinetic phase
      diagrams, both with and without sample rotation, which depict the systematic
      dependence of surface patterns on the shape of energy depositing collision
      cascades after ion impact. Finally, we discuss some results from more recent work
      on surface diffusion with Ehrlich-Schwoebel barriers as the driving force for
      pattern formation during IBS and on Monte Carlo simulations of IBS with
      codeposition of surfactant atoms.

PMID- 21715754
TI  - Kinetic Monte Carlo simulations compared with continuum models and experimental
      properties of pattern formation during ion beam sputtering.
AB  - Kinetic Monte Carlo simulations model the evolution of surfaces during low energy
      ion bombardment using atomic level mechanisms of defect formation, recombination
      and surface diffusion. Because the individual kinetic processes are completely
      determined, the resulting morphological evolution can be directly compared with
      continuum models based on the same mechanisms. We present results of simulations
      based on a curvature-dependent sputtering mechanism and diffusion of mobile
      surface defects. The results are compared with a continuum linear instability
      model based on the same physical processes. The model predictions are found to be
      in good agreement with the simulations for predicting the early-stage
      morphological evolution and the dependence on processing parameters such as the
      flux and temperature. This confirms that the continuum model provides a
      reasonable approximation of the surface evolution from multiple interacting
      surface defects using this model of sputtering. However, comparison with
      experiments indicates that there are many features of the surface evolution that
      do not agree with the continuum model or simulations, suggesting that additional
      mechanisms are required to explain the observed behavior.

PMID- 21715755
TI  - From crater functions to partial differential equations: a new approach to ion
      bombardment induced nonequilibrium pattern formation.
AB  - We develop a methodology for deriving continuum partial differential equations
      for the evolution of large-scale surface morphology directly from molecular
      dynamics simulations of the craters formed from individual ion impacts. Our
      formalism relies on the separation between the length scale of ion impact and the
      characteristic scale of pattern formation, and expresses the surface evolution in
      terms of the moments of the crater function. We demonstrate that the formalism
      reproduces the classical Bradley-Harper results, as well as ballistic atomic
      drift, under the appropriate simplifying assumptions. Given an actual set of
      converged molecular dynamics moments and their derivatives with respect to the
      incidence angle, our approach can be applied directly to predict the presence and
      absence of surface morphological instabilities. This analysis represents the
      first work systematically connecting molecular dynamics simulations of ion
      bombardment to partial differential equations that govern topographic pattern
      forming instabilities.

PMID- 21715756
TI  - A multiscale crater function model for ion-induced pattern formation in silicon.
AB  - The ion-induced formation of nanometer-scale ripples on semiconductors, long
      known as the sputter erosion surface instability, is explained using a coupled
      atomistic-continuum framework. Molecular dynamics simulations of individual
      medium energy ion impacts on an amorphous silicon target show that the average
      effect of an incident ion is to leave an angstrom-scale crater-like impression on
      the surface, complete with a crater rim. The summation of many such impacts on a
      micron-scale surface, combined with the smoothing effect of surface diffusion,
      leads to the formation of surface ripples aligned perpendicular to the projected
      ion beam direction. The same numerical approach can be used to evaluate the
      standard analytical model for this process, known as the Bradley-Harper model.
      Both Bradley-Harper surface evolution and the atomistically determined crater
      function surface evolution are computed over time under conditions similar to
      those for known experimental data. The results show that the surface mass
      rearrangement associated with the finite atomistic crater rims explains a key
      experimental observation, ripple amplitude saturation, which cannot be accurately
      explained using the Bradley-Harper model or any other known numerical or
      analytical model for the sputter erosion surface instability.

PMID- 21715757
TI  - Linear dynamics of ion sputtered surfaces: instability, stability and
      bifurcations.
AB  - The linear dynamics of ion sputtered solids is essential to understanding the
      evolution of ordered and disordered surface patterns. We review the existing
      models of linear dynamics and point out qualitative discrepancies between theory
      and experimental observations that characterize the linear regime. In particular,
      we emphasize the importance of experimental and theoretical analysis of
      bifurcation points: certain values of control parameters such as ion beam angle
      or energy, where flat surfaces undergo a transition from stability to
      instability.

PMID- 21715758
TI  - Coupling of morphology to surface transport in ion-beam-irradiated surfaces:
      normal incidence and rotating targets.
AB  - Continuum models have proved their applicability to describe nanopatterns
      produced by ion-beam sputtering of amorphous or amorphizable targets at low and
      medium energies. Here we pursue the recently introduced 'hydrodynamic approach'
      in the cases of bombardment at normal incidence, or of oblique incidence onto
      rotating targets, known to lead to self-organized arrangements of nanodots. Our
      approach stresses the dynamical roles of material (defect) transport at the
      target surface and of local redeposition. By applying results previously derived
      for arbitrary angles of incidence, we derive effective evolution equations for
      these geometries of incidence, which are then numerically studied. Moreover, we
      show that within our model these equations are identical (albeit with different
      coefficients) in both cases, provided surface tension is isotropic in the target.
      We thus account for the common dynamics for both types of incidence conditions,
      namely formation of dots with short-range order and long-wavelength disorder, and
      an intermediate coarsening of dot features that improves the local order of the
      patterns. We provide for the first time approximate analytical predictions for
      the dependence of stationary dot features (amplitude and wavelength) on
      phenomenological parameters, that improve upon previous linear estimates.
      Finally, our theoretical results are discussed in terms of experimental data.

PMID- 21715759
TI  - Stress-enhanced pattern formation on surfaces during low energy ion bombardment.
AB  - Ion-induced surface patterns (sputter ripples) are observed to grow more rapidly
      than predicted by current models, suggesting that additional sources of
      roughening may be involved. Using a linear stability analysis, we consider the
      contribution of ion-induced stress in the near surface region to the formation
      rate of ripples. This leads to a simple model that combines the effects of stress
      induced roughening with the curvature-dependent erosion model of Bradley and
      Harper. The enhanced growth rate observed on Cu surfaces appears to be consistent
      with the magnitude of stress measured from wafer curvature measurements.

PMID- 21715760
TI  - Applications of metal surfaces nanostructured by ion beam sputtering.
AB  - We review results relative to the formation of regular nanoscale patterns on
      metal substrates exposed to defocused ion beam irradiation. Particular emphasis
      is placed on work which demonstrates the possibility of controllably modifying
      chemico-physical properties of the material by tailoring the nanoscale morphology
      during IBS patterning. Starting from the well-established results found on single
      crystal model systems, we show how the controlled modification of the atomic step
      termination can deeply affect chemical reactivity or magnetic anisotropy. We then
      look in greater detail at the more recent attempts focused on the extension of
      IBS patterning on supported polycrystalline metal films, a promising class of
      systems in view of potential applications. A modification of the functional
      properties of metal films can also be obtained by forcing a shape anisotropy of
      the nanostructures. The modification of the optical response of polycrystalline
      metal nanowires supported on anisotropic templates produced by IBS provides a
      clear example of this.

PMID- 21715761
TI  - Plastic properties of gold surfaces nanopatterned by ion beam sputtering.
AB  - We review the mechanical properties of defective roughened surfaces with the
      major emphasis on nanoindentation work. We also report novel results in which
      force versus penetration curves and AFM images of the nanoindented surface are
      compared for a flat surface of Au(001) and an Ar(+) bombarded one, both with a
      high and a low flux of ions. We have found that bombarded surfaces yield at a
      lower stress than untreated flat ones. Surfaces bombarded at high flux show a
      large roughness and their yield point, marking the onset of surface plasticity,
      decreases with respect to that of the flat surface or of the surface bombarded
      with a low flux. The present results are compared with earlier work on
      nanoindented vicinal surfaces in which the sole surface modifications with
      respect to the flat surface were the presence of a high density of steps. It is
      concluded that a softening effect due to the bombardment-induced nanostructure of
      the surface dominates over the hardening one due to defect creation and
      interaction in the surface neighbourhood.

PMID- 21715762
TI  - Enhancement of antiferromagnetic coupling in magnetic multilayers by low energy
      ion beam substrate nanopatterning.
AB  - Ion beam irradiation has been shown to be an interesting tool for tailoring the
      magnetic properties of thin films and multilayers. The modified properties
      include magnetic anisotropy, interlayer exchange coupling, exchange bias,
      magnetic domain structure and magnetization reversal. In this work, new results
      are shown concerning the enhancement, by one order of magnitude, of the
      antiferromagnetic coupling strength in amorphous CoSi/Si multilayers by
      irradiating Si(100) substrates with 1 keV Ar(+) ions. The ion beam exposure
      induces an increase of the substrate roughness, from 0.07 to 0.88 nm, which
      enhances antiferromagnetic coupling in the magnetic multilayers grown on top. One
      possible mechanism governing this enhancement is discussed, related to the
      formation of magnetic/non-magnetic regions where dipolar interactions could
      stabilize the antiferromagnetic alignment. The presence of non-magnetic regions
      is suggested by the observed trend to superparamagnetism, and is expected since
      the Curie temperature of the amorphous CoSi alloy used is slightly above but very
      close to room temperature. Accordingly, small fluctuations in the local
      composition, leading to an enrichment of Si, would produce non-magnetic regions
      enabling dipolar interactions to take place. Furthermore, the ion beam induced
      increase of roughness makes surface diffusion of the atoms arriving at the sample
      difficult, favoring the formation of local non-magnetic inhomogeneities. Finally,
      the role of other possible mechanisms to enhance antiferromagnetic coupling is
      also briefly discussed.

PMID- 21715763
TI  - Ion beam sputtered nanostructured semiconductor surfaces as templates for
      nanomagnet arrays.
AB  - The ongoing tendency for increasing the storage densities in magnetic recording
      techniques requires a search for efficient routes to fabricate and characterize
      nanomagnet arrays on solid supports. Spontaneous pattern formation in
      semiconductor heteroepitaxy or under ion erosion of semiconductor surfaces yields
      nanostructured substrates that can serve as templates for subsequent deposition
      of magnetic material. The nanostructured morphology of the template can easily be
      replicated into the magnetic coating by means of the shadow deposition technique
      which allows one to selectively cover specific areas of the template with
      magnetic material. Here, we demonstrate that ion bombardment induced hexagonally
      arranged GaSb dots are suitable templates for fabricating by shadow deposition
      close-packed nanomagnets with a lateral extension of <=50 nm, i.e. with a
      resulting storage density of up to 0.2 Tbit in(-2). Magnetic-force microscopy
      (MFM) measurements revealed that the individual nanomagnets-which are located on
      the tops of the semiconductor hillocks-are single domain and show mainly
      independent magnetization. The coupling behaviour was estimated from correlation
      function analysis of the MFM data. In addition, magneto-optical Kerr effect
      measurements demonstrate that the nanomagnets can be magnetized either out-of
      plane or in-plane and show remanence at room temperature, with a coercive field
      of 120 mT.

PMID- 21715764
TI  - Large area smoothing of surfaces by ion bombardment: fundamentals and
      applications.
AB  - Ion beam erosion can be used as a process for achieving surface smoothing at
      microscopic length scales and for the preparation of ultrasmooth surfaces, as an
      alternative to nanostructuring of various surfaces via self-organization. This
      requires that in the evolution of the surface topography different relaxation
      mechanisms dominate over the roughening, and smoothing of initially rough
      surfaces can occur. This contribution focuses on the basic mechanisms as well as
      potential applications of surface smoothing using low energy ion beams. In the
      first part, the fundamentals for the smoothing of III/V semiconductors, Si and
      quartz glass surfaces using low energy ion beams (ion energy: <=2000 eV) are
      reviewed using examples. The topography evolution of these surfaces with respect
      to different process parameters (ion energy, ion incidence angle, erosion time,
      sample rotation) has been investigated. On the basis of the time evolution of
      different roughness parameters, the relevant surface relaxation mechanisms
      responsible for surface smoothing are discussed. In this context, physical
      constraints as regards the effectiveness of surface smoothing by direct ion
      bombardment will also be addressed and furthermore ion beam assisted smoothing
      techniques are introduced. In the second application-orientated part, recent
      technological developments related to ion beam assisted smoothing of optically
      relevant surfaces are summarized. It will be demonstrated that smoothing by
      direct ion bombardment in combination with the use of sacrificial smoothing
      layers and the utilization of appropriate broad beam ion sources enables the
      polishing of various technologically important surfaces down to 0.1 nm root mean
      square roughness level, showing great promise for large area surface processing.
      Specific examples are given for ion beam smoothing of different optical surfaces,
      especially for substrates used for advanced optical applications (e.g., in x-ray
      optics and components for extreme ultraviolet lithography).

PMID- 21715765
TI  - Adsorption of benzene, phenol, propane and carbonic acid molecules on oxidized
      Al(111) and alpha- Al(2)O(3)(0001) surfaces: a first-principles study.
AB  - We present the results of ab initio calculations describing the adsorption of
      certain small organic molecules on clean and oxidized Al(111) surfaces as well as
      on the alpha- Al(2)O(3)(0001) surface. Our results show that adsorption of
      benzene on the clean and oxidized Al(111) surfaces is generally weak, the
      adsorption energy being at most around -0.5 eV per benzene molecule, and the
      molecule adsorbed at a considerable distance from the surfaces. The adsorption
      energy varies weakly at the different adsorption sites and as a function of the
      oxygen coverage. For the alumina surface, we find no benzene adsorption at all.
      We have also calculated for a phenol molecule on the aluminum and alumina
      surfaces, since it is similar to the benzene molecule. The results show a weak
      adsorption for phenol on the alumina surface and no adsorption on the aluminum or
      oxidized aluminum surfaces at all. For the propane molecule there is no
      adsorption on either the oxidized aluminum or the alumina surface, whereas the
      carbonic acid molecule binds strongly to the alumina but not to the aluminum
      surface.

PMID- 21715766
TI  - Interfacial potentials for Al/SiC(111).
AB  - To study the metal/semiconductor interface by means of atomistic simulation, an
      effective interfacial potential is an important issue. In this work, ab initio
      adhesive energies are used to derive interfacial potentials for the Al/SiC(111)
      interface. In order to describe the directional covalent bonds at the interface,
      we suggest a potential model comprising both two-body and three-body terms. The
      former is a parameter-free potential obtained by a lattice inversion method and
      the latter is assigned in modified Stillinger-Weber potential form. The obtained
      potentials are used to study the position of misfit dislocations in the
      Al/SiC(111) interface. There is a coherent Al interlayer on the interface plane
      and the dislocation appears on the Al side.

PMID- 21715767
TI  - The origin of preferred orientation during carbon film growth.
AB  - Carbon films were prepared using a filtered cathodic vacuum arc deposition system
      operated with a substrate bias varying linearly with time during growth. Ion
      energies were in the range between 95 and 620 eV. Alternating dark, high density
      (sp(3) rich) bands and light, low density (sp(2) rich) bands were observed using
      cross-sectional transmission electron microscopy, corresponding to abrupt
      transitions between materials with densities of approximately 3.1 and 2.6 g cm(
      3). No intermediate densities were observed in the samples. The low density bands
      show strong preferred orientation with graphitic sheets aligned normal to the
      film. After annealing, the low density bands became more oriented and the thinner
      high density layers were converted to low density material. In molecular dynamics
      modelling of film growth, temperature activated structural rearrangements
      occurring over long timescales ([Formula: see text] ps) caused the transition
      from sp(3) rich to oriented sp(2) rich structure. Once this oriented growth was
      initiated, the sputtering yield decreased and channelling was observed. However,
      we conclude that sputtering and channelling events, while they occur, are not the
      cause of the transition to the oriented structure.

PMID- 21715768
TI  - Scanning tunneling spectrum of electrons confined in a rectangular quantum
      corral.
AB  - We obtained the scanning tunneling spectrum (STS) of an electron confined in a
      rectangular quantum corral by considering the electron to be in a quasi
      stationary state. Because of non-hermiticity of the Hamiltonian, the electron has
      a complex eigenenergy. The imaginary part gives the peak width coming mainly from
      the electron tunneling through a corral barrier. Our STS is consistent with the
      experimental spectrum that had been measured for electrons confined in a
      rectangular quantum corral. We obtained peak widths against energy levels and
      components of the STS which are constructed with quasi-stationary eigenstates. It
      is shown that normalization of a wavefunction by considering its time evolution
      is decisive in obtaining the proper STS. Moreover, we specified the position
      dependence of STS in relation to the image of the surface local density of
      states.

PMID- 21715769
TI  - Surface segregation of Si and its effect on oxygen adsorption on a gamma
      TiAl(111) surface from first principles.
AB  - We perform first-principles calculations based on the density-functional theory
      to study the surface segregation of Si and its effect on the oxygen adsorption on
      a gamma-TiAl(111) surface for a range of oxygen coverage 0<Theta<=1.0 monolayer
      (ML). The calculated results show that the alloying Si atoms prefer occupying
      surface Ti sites to the sites in the bulk of gamma-TiAl, which suggests the
      occurrence of Si surface segregation. When oxygen atoms adsorb on a pure gamma
      TiAl(111) surface, the most favorable sites are the adsorption sites with more Ti
      atoms as their nearest neighbors in the surface layer at all the calculated
      coverages and the interactions between adsorbed oxygen atoms are repulsive.
      However, when oxygen atoms adsorb on an Si-alloyed gamma-TiAl(111) surface, the
      interactions between the adsorbed oxygen atoms are attractive at oxygen coverage
      0<Theta<=1.0 ML. Meanwhile, the interactions between O and Al atoms become
      stronger whereas those between O and Ti atoms become weaker relative to oxygen
      adsorbed on a pure gamma-TiAl(111) surface. The atomic geometry and density of
      state are analyzed. The results show that the surface ripple of the top metal
      layer for oxygen on a pure gamma-TiAl(111) surface is Ti upwards, while that for
      oxygen on an Si-alloyed gamma-TiAl(111) surface is Al upwards at high oxygen
      coverage (Theta>=0.50 ML). This effect of Si is of benefit to the nucleation of
      alumina, which is attributed to Si surface segregation and an increase of the
      surface Al:Ti ratio. This can help to explain why alloying the gamma-TiAl(111)
      surface with Si could favor the formation of the Al(2)O(3) scale at the first
      stage and result in good oxidation resistance in experiments.

PMID- 21715770
TI  - Zinc phthalocyanine thin film and chemical analyte interaction studies by density
      functional theory and vibrational techniques.
AB  - Thin films of zinc phthalocyanine have been deposited on KBr and glass substrates
      by the thermal evaporation method and characterized by the x-ray diffraction,
      optical, infrared and Raman techniques. The observed x-ray diffraction and
      infrared absorption spectra of as-deposited thin films suggest the presence of an
      alpha crystalline phase. Infrared and Raman spectra of thin films after exposure
      to vapours of ammonia and methanol have also been recorded. Shifts in the
      position of some IR and Raman bands in the spectra of exposed films have been
      observed. Some bands also show changes in their intensity on exposure. Increased
      charge on the phthalocyanine ring and out-of-plane distortion of the core due to
      interaction between zinc phthalocyanine and vapour molecules involving the fifth
      coordination site of the central metal ion may be responsible for the band
      shifts. Changes in the intensity of bands are interpreted in terms of the
      lowering of molecular symmetry from D(4h) to C(4v) due to doming of the core.
      Molecular parameters and Mulliken atomic charges of zinc phthalocyanine and its
      complexes with methanol and ammonia have been calculated from density functional
      theory. The binding energy of the complexes have also been calculated. Calculated
      values of the energy for different complexes suggest that axially coordinated
      vapour molecules form the most stable complex. Calculated Mulliken atomic charges
      show net charge transfer from vapour molecules to the phthalocyanine ring for the
      most stable complex.

PMID- 21715771
TI  - Theoretical study of multiferroic thin films based on a microscopic model.
AB  - The influence of the surface, film thickness, temperature and ion doping effects
      on the magnetic and electric properties in multiferroic thin films is studied by
      a combination of modified Heisenberg and transverse Ising models using a Green's
      function technique. It is demonstrated that the magnetization M, the polarization
      P, the critical temperatures T(N) and T(C), the spin-wave energies E(m) and E(e),
      and their damping are very sensitive to the exchange interaction constants on the
      surface (A(1s) and J(s)) and in the defect layers (A(1d) and J(d)). It has been
      found that the damping is enhanced compared to the case with no defect layers. We
      have obtained that M, P, T(N), T(C) and the spin-wave energies could be increased
      or decreased by using different kinds of doping ions. The concurrent interaction
      mechanisms of the magnetic and electric subsystems are shown. The results are in
      qualitative accordance with the experimental data.

PMID- 21715772
TI  - In situ stress evolution during and after sputter deposition of Al thin films.
AB  - The stress, growth, and morphology evolution of Al thin films up to 300 nm thick,
      sputter deposited at a constant rate of 0.04 nm s(-1) onto thermally oxidized
      Si(100) substrates have been investigated for various sputter pressures in the
      range from 0.05 to 6 Pa. The stress evolution has been studied during and after
      the film deposition by means of in situ substrate curvature measurements using an
      optical two-beam deflection method. In order to obtain insight into the
      mechanisms of stress generation and relaxation, the microstructure of the films
      was investigated by scanning electron microscopy, focused-ion-beam microscopy,
      and atomic force microscopy. The stress evolution during the early stage of
      deposition of films is consistent with the Volmer-Weber growth mode known for
      metals with high adatom mobility. For thicker films, the compressive stress
      increases in the sputter pressure range of 0.05-0.5 Pa, whereas at even higher
      sputter pressures a transition from compressive to tensile stress takes place.
      This transition is correlated with a change from a relatively dense to a more
      porous microstructure characterized by decreasing mass density and increasing
      electrical resistivity with increasing sputter pressure. The dependence of the
      stress and microstructure on the sputter pressure can be consistently understood
      through a combination of the stress mechanisms for vapor and sputter deposited
      films proposed in the literature.

PMID- 21715773
TI  - Quantum scattering of neon from a nanotextured surface.
AB  - Phonon exchange is the usual cause of decoherence in atom-surface scattering. By
      including quantum effects in the treatment of Debye-Waller scattering, we show
      that phonon exchange becomes ineffective when the relevant phonon frequencies are
      high. The result explains the surprising observation of strong elastic scattering
      of Ne from a Cu(100) surface nanotextured with a c(2 * 2) Li adsorbate structure.
      We extend a previous model to describe the phonon spectra by an Einstein
      oscillator component with an admixture of a Debye spectrum. The Einstein
      oscillator represents the dominant, high frequency vibration of the adsorbate,
      normal to the surface, while the Debye spectrum represents the substrate
      contribution. Neon scattering is so slow that exciting the adsorbate mode has a
      low probability and is impossible if the incident energy is below the threshold.
      Thus, adsorbate vibrations are averaged out. A theoretical discussion and
      calculation shows that under such circumstances the vibrations of a light
      adsorbate do not contribute to the Debye-Waller effect, with the result that Ne
      scattering at thermal energies is quantum mechanical and largely elastic,
      explaining the high reflectivity and the diffraction peaks observed
      experimentally.

PMID- 21715774
TI  - Superconductivity in undoped single crystals of BaFe(2)As(2): field and current
      dependence.
AB  - In previous work on undoped MFe(2)As(2), partial drops in the resistivity
      indicative of traces of superconductivity have been observed for some samples
      with M =  Ba (T(c)~20 K, up to 25% drop in rho) and M =  Ca (T(c)~10 K, up to 45%
      drop in rho). A complete drop in the resistivity to rho = 0, along with a finite
      fraction of Meissner flux expulsion, has been observed for M  = Sr, T(c) = 22 K.
      Using In-flux grown single crystal samples of undoped BaFe(2)As(2), we find a
      complete drop in the resistivity to 0 for most samples beginning at T(c)(onset) =
      22.5 K. However-in contrast to the SrFe(2)As(2) results-there is no measurable
      Meissner effect and no suppression of the resistive superconducting transition
      with annealing. The current sensitivity of the superconducting resistive
      transition in our samples of BaFe(2)As(2) is quite strong, with an increase in
      the current density of a factor of 15 to ~1.5 A cm(-2) not changing T(c)(onset)
      but broadening the transition significantly and causing rho to remain finite as
      [Formula: see text]. To investigate whether this unusually low critical current
      is indicative of filamentary conduction lacking the apparent anisotropy seen in
      the critical magnetic field, H(c2), measurements for, e.g., the bulk
      superconductor Co-doped BaFe(2)As(2), H(c2) was measured in both crystalline
      directions. These BaFe(2)As(2) samples show H(c2)(T) values in the ab-plane and
      along the c-axis comparable to those seen for BaFe(2-x)Co(x)As(2), which has a
      similar T(c). Since the lack of T(c) suppression after annealing argues against
      strain-induced superconductivity as proposed for the other undoped MFe(2)As(2)
      materials, another possible cause for the superconductivity in BaFe(2)As(2) is
      discussed.

PMID- 21715775
TI  - Hubbard-U band-structure methods.
AB  - The last decade has seen a large increase in the number of electronic-structure
      calculations that involve adding a Hubbard term to the local-density
      approximation band-structure Hamiltonian. The Hubbard term is then determined
      either at the mean-field level or with sophisticated many-body techniques such as
      using dynamical mean-field theory. We review the physics underlying these
      approaches and discuss their strengths and weaknesses in terms of the larger
      issues of electronic structure that they involve. In particular, we argue that
      the common assumptions made to justify such calculations are inconsistent with
      what the calculations actually do. Although many of these calculations are often
      treated as essentially first-principles calculations, in fact, we argue that they
      should be viewed from an entirely different point of view, namely, as based on
      phenomenological many-body corrections to band-structure theory. Alternatively,
      it may also be considered that they are just based on a Hubbard model that is
      more complex than the simple one- or few-band models traditionally used in many
      body theories of solids.

PMID- 21715776
TI  - Velocity saturation in intrinsic graphene.
AB  - We study the transport of carriers in intrinsic graphene by means of an ensemble
      Monte Carlo technique. Scattering by acoustic and optical phonons dominates the
      transport. We find that velocity 'saturation' sets in at relatively low values of
      the electric field, but that the value is dependent upon the carrier density.
      Velocity overshoot is also observed to occur in these simulations.

PMID- 21715777
TI  - Dirac electrons in graphene-based quantum wires and quantum dots.
AB  - In this paper we analyse the electronic properties of Dirac electrons in finite
      size ribbons and in circular and hexagonal quantum dots. We show that due to the
      formation of sub-bands in the ribbons it is possible to spatially localize some
      of the electronic modes using a p-n-p junction. We also show that scattering of
      confined Dirac electrons in a narrow channel by an infinitely massive wall
      induces mode mixing, giving a qualitative reason for the fact that an analytical
      solution to the spectrum of Dirac electrons confined in a square box has not yet
      been found. A first attempt to solve this problem is presented. We find that only
      the trivial case k = 0 has a solution that does not require the existence of
      evanescent modes. We also study the spectrum of quantum dots of graphene in a
      perpendicular magnetic field. This problem is studied in the Dirac approximation,
      and its solution requires a numerical method whose details are given. The
      formation of Landau levels in the dot is discussed. The inclusion of the Coulomb
      interaction among the electrons is considered at the self-consistent Hartree
      level, taking into account the interaction with an image charge density necessary
      to keep the back-gate electrode at zero potential. The effect of a radial
      confining potential is discussed. The density of states of circular and hexagonal
      quantum dots, described by the full tight-binding model, is studied using the
      Lanczos algorithm. This is necessary to access the detailed shape of the density
      of states close to the Dirac point when one studies large systems. Our study
      reveals that zero-energy edge states are also present in graphene quantum dots.
      Our results are relevant for experimental research in graphene nanostructures.
      The style of writing is pedagogical, in the hope that newcomers to the subject
      will find this paper a good starting point for their research.

PMID- 21715778
TI  - Transmission and scarring in graphene quantum dots.
AB  - We study electronic transport in quantum-dot structures made of graphene.
      Focusing on the rectangular dot geometry and utilizing the non-equilibrium
      Green's function to calculate the transmission in the tight-binding framework, we
      find significant fluctuations in the transmission as a function of the electron
      energy. The fluctuations are correlated with the formation of quantum scarring
      states, or pointer states in the dot. Both enhancement and suppression of
      transmission have been observed. As the size of the quantum dot is increased,
      more scarring states can be formed, leading to stronger transmission or
      conductance fluctuations.

PMID- 21715779
TI  - Quantum transport through a graphene nanoribbon-superconductor junction.
AB  - We study the electron transport through a graphene nanoribbon-superconductor
      junction. Both zigzag and armchair edge graphene nanoribbons are considered, and
      the effects of the magnetic field and disorder on the transport property are
      investigated. By using the tight-binding model and the non-equilibrium Green's
      function method, the expressions of the current, conductance, normal tunneling
      coefficient and Andreev reflection coefficient are obtained. For a clean system
      and at zero magnetic field, the linear conductance increases approximately in a
      linear fashion with the on-site energy. In the presence of a magnetic field and a
      moderate disorder, the linear conductance exhibits plateau structures for both
      armchair and zigzag edges. The plateau values increase with the width of the
      graphene ribbon. With a wide sample width, a saturated plateau value of
      |nu|e(2)/h emerges at the filling factor nu. For a small filling factor, the
      conductance can reach the saturated value at a small width, but for a high
      filling factor it requires to have a quite wide sample width to reach the
      saturated value. In particular, the Andreev reflection coefficient is always at
      0.5 after reaching the saturated value, independent of any system parameters. In
      addition, we also consider the finite bias case, in which the Andreev reflection
      coefficient and normal tunneling coefficient are studied.

PMID- 21715780
TI  - Chemical functionalization of graphene.
AB  - Experimental and theoretical results on chemical functionalization of graphene
      are reviewed. Using hydrogenated graphene as a model system, general principles
      of the chemical functionalization are formulated and discussed. It is shown that,
      as a rule, 100% coverage of graphene by complex functional groups (in contrast
      with hydrogen and fluorine) is unreachable. A possible destruction of graphene
      nanoribbons by fluorine is considered. The functionalization of infinite graphene
      and graphene nanoribbons by oxygen and by hydrofluoric acid is simulated step by
      step.

PMID- 21715781
TI  - On spectral properties of bilayer graphene: the effect of an SiC substrate and
      infrared magneto-spectroscopy.
AB  - We investigate the effect of asymmetry in bilayer graphene induced by a diatomic
      substrate (such as SiC) and its influence on the bilayer spectrum in zero and
      strong magnetic fields. We also determine selection rules for inter-Landau level
      transitions, taking into account all four pi bands.

PMID- 21715782
TI  - A high-magnetic-field-induced density-wave state in graphite.
AB  - Whilst the realization of graphene, probably one of the best two-dimensional
      carrier systems to study, has attracted much research interest recently,
      graphite, which may be regarded as multi-layered graphene, has also been known to
      exhibit very interesting phenomena at high magnetic fields and low temperatures.
      The electron-hole system in the compensated semimetal graphite undergoes a
      magnetic-field-induced electronic phase transition and successive transitions,
      including a reentrant transition back to the normal phase, at higher magnetic
      fields. In this article, we review the physics of the high-magnetic-field phase
      of graphite and elaborate on our studies on this subject using pulsed high
      magnetic fields.

PMID- 21715783
TI  - The size effect in the equation of state for nanostructures.
AB  - In analogy to the interacting real gas the magnetic systems are described like
      magnons which form the system of interacting quasi-particles. In order to
      describe the magnetic systems, firstly the equation of state for real gas is
      introduced and next the model is developed in the case of magnons for the
      confined geometry. In particular, the applications of magnetic equation of states
      for thin films and nanowires with unit cell cross sections as well as for
      nanoparticles are considered. Moreover, the size effect and the critical
      temperature for the mentioned systems are investigated. The critical temperature
      and magnetization exhibit a strong dependence on the size of the system and the
      anisotropy of magnetic interaction in the interior and at the surface of the
      considered system.

PMID- 21715784
TI  - The Peierls stress of the moving [Formula: see text] screw dislocation in Ta.
AB  - The Peierls stress of the moving [Formula: see text] screw dislocation with a
      planar and non-dissociated core structure in Ta has been calculated. The elastic
      strain energy which is associated with the discrete effect of the lattice and
      ignored in classical Peierls-Nabarro (P-N) theory has been taken into account in
      calculating the Peierls stress, and it can make the Peierls stress become
      smaller. The Peierls stress we obtain is very close to the experimental data. As
      shown in the numerical calculations and atomistic simulations, the core structure
      of the screw dislocation undergoes significant changes under the explicit stress
      before the screw dislocation moves. Moreover, the mechanism of the screw
      dislocation is revealed by our results and the experimental data that the screw
      dislocation retracts its extension in three {110} planes and transforms its
      dissociated core structure into a planar configuration. Therefore, the core
      structure of the moving [Formula: see text] screw dislocation in Ta is proposed
      to be planar.

PMID- 21715785
TI  - New 2-methylimidazole-dicarboxylic acid molecular crystals: crystal structure and
      proton conductivity.
AB  - Three new proton conducting molecular crystals, 2-methylimidazole glutarate, 2
      methylimidazole suberate and 2-methylimidazole azelate, were obtained and their
      structure was determined by the x-ray diffraction method. The structure of the
      crystals was found to be of layer-type. A hydrogen bond network between the
      heterocycle, glutaric acid and water molecules was apparent in a single layer of
      2-methylimidazole glutarate, whereas chains consisting of two heterocyclic
      molecules linked with hydrogen bonds with dicarboxylic acid were distinguished in
      a single layer of 2-methylimidazole suberate and azelate crystals. Thermal
      stability of the crystals was characterized by differential scanning calorimetry
      and the electrical conductivity was studied by the impedance spectroscopy method.
      The maximum conductivity of 2-methylimidazole glutarate pellets amounts to 3.3 *
      10(-2) S m(-1) at 325 K, in the case of 2-methylimidazole suberate pellets the
      maximum conductivity is 2.4 * 10(-4) S m(-1) at 348 K and for 2-methylimidazole
      azelate pellets the maximum conductivity reaches 6.9 * 10(-4) S m(-1) at 353 K.

PMID- 21715786
TI  - Self-consistent aspects of x-ray absorption calculations.
AB  - We implemented a self-consistent, real-space x-ray absorption calculation within
      the FDMNES code. We performed the self-consistency within several schemes and
      identified which one is the most appropriate. We show a method that allows a
      rigorous setting of the Fermi level and thus an estimation of the energy cutoff
      for the identification and elimination of the occupied states. We investigated
      what are the structures where one can afford performing the self-consistent
      calculation at a lesser cluster radius than the absorption one. We exemplify the
      effects of the self-consistency at the K-edge and for several reference cases,
      including the copper Cu and the rutile TiO(2). We verified the robustness of our
      procedure on the transitional 3d and 4d elements. Although amelioration can be
      noticed, the self-consistency performed at the K-edge does not bring a major
      improvement of the calculated spectra. Taking into consideration a non-self
      consistent, non-spherical potential gives better results than a self-consistent
      muffin-tin approximation calculation.

PMID- 21715787
TI  - Identifying valence structure in LiFeAs and NaFeAs with core-level spectroscopy.
AB  - Resonant x-ray emission spectroscopy (XES) measurements at Fe L(2,3) edges and
      electronic structure calculations for LiFeAs and NaFeAs are presented. Experiment
      and theory show that in the vicinity of the Fermi energy, the density of states
      is dominated by contributions from Fe 3d states. The comparison of Fe L(2,3) XES
      with spectra of related FeAs compounds reveals similar trends in energy and the
      ratio of intensities of the L(2) and L(3) peaks (I(L(2))/I(L(3)) ratio). The
      I(L(2))/I(L(3)) ratio for all FeAs-based superconductors is found to be closer to
      that of metallic Fe than that of the strongly correlated FeO. We conclude that
      iron-based superconductors are weakly or, at most, moderately correlated systems.

PMID- 21715788
TI  - Properties of the relaxation time distribution underlying the Kohlrausch-Williams
      Watts photoionization of the DX centers in Cd(1-x)Mn(x)Te mixed crystals.
AB  - In this paper we clarify the relationship between the relaxation rate and
      relaxation time distributions underlying the Kohlrausch-Williams-Watts (KWW)
      photoconductivity build-ups in indium- and gallium-doped Cd(1-x)Mn(x)Te mixed
      crystals. We discuss the role of asymptotic properties of the corresponding
      probability density functions. We show that the relaxation rate distribution, as
      a completely asymmetric alpha-stable distribution, leads to an infinite mean
      value of the effective relaxation rate. In contrast, the relaxation time
      distribution related to it leads to a finite mean value of the effective
      relaxation time. It follows from the experimental data analysis that for all the
      investigated samples the KWW exponent alpha decreases linearly with increasing
      photon flux in the range of (0.6-0.99) and its values are more spread in the case
      of gallium-doped material. We also observe a linear dependence of the mean
      relaxation time on the characteristic material time constant, which is consistent
      with the theoretical model.

PMID- 21715789
TI  - First-principles study of diffusion of Li, Na, K and Ag in ZnO.
AB  - Based on ab initio total energy calculations, Li, Na and Ag interstitials are
      found to be stable with at least a 1.56 eV energy barrier to transform to a zinc
      substitutional site in ZnO, whereas K interstitial has a relatively small energy
      barrier at 0.79 eV. The isolated dopant substitutional defects (Li(Zn), Na(Zn),
      K(Zn) and Ag(Zn)) are found to be rather stable, with at least a 3.4 eV energy
      barrier to transform to an interstitial site. All of the dopant interstitials
      (Li(i), Na(i), K(i) and Ag(i)) are fast diffusers. The diffusion of Li
      interstitial is isotropic, whereas the diffusion of Na, K and Ag interstitials is
      highly anisotropic. Fundamental processes of the vacancy-assisted mechanisms are
      systematically investigated and specific values of the energy barriers are
      obtained.

PMID- 21715790
TI  - Fundamental relation between longitudinal and transverse conductivities in the
      quantum Hall system.
AB  - We investigate the relation between the diagonal (sigma(xx)) and off-diagonal
      (sigma(xy)) components of the conductivity tensor in the quantum Hall system. We
      calculate the conductivity components for a short-range impurity potential using
      the linear response theory, employing an approximation that simply replaces the
      self-energy by a constant value [Formula: see text] with tau the scattering time.
      The approximation is equivalent to assuming that the broadening of a Landau level
      due to disorder is represented by a Lorentzian with the width [Formula: see
      text]. Analytic formulae are obtained for both sigma(xx) and sigma(xy) within the
      framework of this simple approximation at low temperatures. By examining the
      leading terms in sigma(xx) and sigma(xy), we find a proportional relation between
      dsigma(xy)/dB and Bsigma(xx)(2). The relation, after slight modification to
      account for the long-range nature of the impurity potential, is shown to be in
      quantitative agreement with experimental results obtained in the GaAs/AlGaAs two
      dimensional electron system at the low magnetic field regime where spin splitting
      is negligibly small.

PMID- 21715791
TI  - Magnetoresistance of magnetically doped ZnO films.
AB  - Magnetoresistance measurements have been made at 5 K on doped ZnO thin films
      grown by pulsed laser deposition. ZnCoO, ZnCoAlO and ZnMnAlO samples have been
      investigated and compared to similar films containing no transition metal
      dopants. It is found that the Co-doped samples with a high carrier concentration
      have a small negative magnetoresistance, irrespective of their magnetic moment.
      On decreasing the carrier concentration, a positive contribution to the
      magnetoresistance appears and a further negative contribution. This second,
      negative contribution, which occurs at very low carrier densities, correlates
      with the onset of ferromagnetism due to bound magnetic polarons suggesting that
      the negative magnetoresistance results from the destruction of polarons by a
      magnetic field. An investigation of the anisotropic magnetoresistance showed that
      the orientation of the applied magnetic field, relative to the sample, had a
      large effect. The results for the ZnMnAlO samples showed less consistent trends.

PMID- 21715792
TI  - Effect of oxygen content on the magnetic properties of multiferroic
      YMn(2)O(5+delta).
AB  - The effect of oxygen content on magnetic properties in the multiferroic
      YMn(2)O(5+delta) system was investigated with samples prepared under different
      oxygen pressures. Our results show that, with increasing oxygen content, the
      magnetic response changes from being dominated by the anomaly at ~45 K to the one
      around 20 K. However, specific heat measurements and neutron powder diffraction
      studies indicate that the presence of the magnetic transition at ~45 K is
      independent of oxygen content. The results suggest that oxygen nonstoichiometry
      can be one important degree of freedom in manipulating the multiferroic
      properties.

PMID- 21715793
TI  - Magnetic and crystallographic characterization of Pt(3)Mn(x)Cr(1-x) by XMCD and x
      ray diffraction.
AB  - We have performed XMCD and diffraction measurements on the Pt(3)Mn(x)Cr(1-x)
      alloy, which show that the magnetization of Pt is independently influenced by the
      Mn or Cr 3d orbital. We find that the magnetic moment on Pt, and its
      decomposition into spin and orbital components, is uniquely determined by the
      relative number of Mn and Cr neighbors. We then investigate the effect of
      pressure on the magnetization of Pt in the Pt(3)Mn(0.5)Cr(0.5) alloy. Our high
      pressure data enable us to conclude that at 14 GPa the spin and orbital
      polarization of the Pt 5d band are augmented by about 70%, with no interaction
      between them.

PMID- 21715794
TI  - Muon-fluorine entanglement in fluoropolymers.
AB  - We present the results of muon spin relaxation measurements on the fluoropolymers
      polytetrafluoroethylene (PTFE), poly(vinylidene fluoride) (PVDF) and poly(vinyl
      fluoride) (PVF). Entanglement between the muon spin and the spins of the fluorine
      nuclei in the polymers allows us to identify the different muon stopping states
      that occur in each of these materials and provides a method of probing the local
      environment of the muon and the dynamics of the polymer chains.

PMID- 21715795
TI  - The two-dimensional site-diluted Ising model: a short-time-dynamics approach.
AB  - The site-diluted Ising ferromagnet is investigated on a square lattice, within
      short-time-dynamics numerical simulations, for different site concentrations. The
      dynamical exponents theta and z are obtained and it is shown that these exponents
      do depend strongly on the disorder, exhibiting a clear breakdown of universality,
      characterized by relative variations of nearly 100% in the range of site
      concentrations investigated. In what concerns the static exponents beta and nu,
      universality is preserved within the error bars.

PMID- 21715796
TI  - The effect of the ferroelectric domain walls in the scanning near field optical
      microscopy response of periodically poled Ba(2)NaNb(5)O(15) and LiNbO(3)
      crystals.
AB  - A study of Ba(2)NaNb(5)O(15) and LiNbO(3) crystals with periodic ferroelectric
      domain structures using the scanning near field optical microscopy technique is
      reported. Optical contrast is observed in the regions of ferroelectric domain
      boundaries and it is analysed using beam propagation method modelling. This
      reveals that the optical contrast, a consequence of changes in the refractive
      index, is not due to variation of the waveguide-coupling efficiency, and supports
      the hypothesis that it is associated with the domain array, which is related to
      the size of the domain.

PMID- 21715797
TI  - The Almeida-Thouless line in BiFeO(3): is bismuth ferrite a mean field spin
      glass?
AB  - Low-temperature magnetic properties of epitaxial BiFeO(3) (BFO) thin films grown
      on (111) SrTiO(3) substrates have been studied. Zero-field-cooled and field
      cooled magnetization curves show a large discrepancy beginning at a
      characteristic temperature T(f) that is dependent on the magnetic field strength.
      T(f)(H) varies according to the well known de Almeida-Thouless line [Formula: see
      text] suggesting an acentric long-range spin-glass behavior and mean field
      system.

PMID- 21715798
TI  - Raman-active modes in homogeneous and inhomogeneous bundles of single-walled
      carbon nanotubes.
AB  - In the present work, the non-resonant Raman-active modes are calculated for
      several diameters, chiralities and sizes for homogeneous and inhomogeneous
      bundles of single-walled carbon nanotubes (BWCNTs), using the spectral moment's
      method (SMM). Additional intense Raman-active modes are present in the breathing
      like modes (BLM) spectra of these systems in comparison with a single fully
      symmetric A(1g) mode characteristic of isolated nanotubes (SWCNTs). The
      dependence of the wavenumber of these modes in terms of diameters, lengths and
      number of tubes was investigated. We found that, for a finite (in)homogeneous
      bundle, additional breathing-like modes appear as a specific signature.

PMID- 21715799
TI  - Electron-ion quantum plasma excitations in single-walled carbon nanotubes.
AB  - The effect of a uniform static external magnetic field in the Voigt configuration
      on electron-ion quantum plasma oscillations in single-walled carbon nanotubes is
      discussed using the linearized quantum hydrodynamic model in conjunction with
      Maxwell's equations. Transverse magnetic waves which propagate parallel to the
      surface of the nanotubes, in the presence of an external magnetic field, yield a
      spectrum containing a quantum magnetosonic branch in addition to the
      magnetoplasmon branch.

PMID- 21715800
TI  - Structure and stability of Mg-intercalated boron nanotubes and crystalline
      bundles.
AB  - First principles calculations based on density functional theory predict a highly
      selective adsorption site for Mg atoms and negligible preference for the growth
      of Mg islands on the tubular surface of Mg-intercalated (small diameter) boron
      nanotubes, thereby establishing the criterion for understanding the growth
      mechanism of single-walled boron nanotubes (SWBNTs) supported by magnesium. On
      the other hand, the Mg-SWBNT bundles can be considered as an 'electrostatic'
      bound system consisting of partially ionized Mg and partially ionized tubules.
      The metallic character of the tubular Mg-B bundles is then attributed to boron
      atoms forming a metallic wire, while the role of Mg atoms is limited in enhancing
      the stability of the crystalline bundles.

PMID- 21715801
TI  - Tunneling of Dirac electrons through one-dimensional potentials in graphene: a T
      matrix approach.
AB  - The standard T-matrix method can be effectively used for studying the dynamics of
      Dirac electrons under one-dimensional potentials in graphene. The transmission
      probability expressed in terms of T-matrices and the corresponding ballistic
      current are derived for any smooth one-dimensional potential, taking into account
      the chirality of Dirac massless carriers. Numerical calculations are illustrated
      for the potential approximately describing graphene n-p junctions.

PMID- 21715802
TI  - First-principles super-cell investigation of the rattling effect in Li-doped KCl.
AB  - We have studied by the first-principles total energy method the off-center
      instability of a substitutional Li impurity in KCl. We report here the results of
      super-cell calculations of the energy associated with displacing the Li along
      [Formula: see text], [Formula: see text] and [Formula: see text] directions
      relative to the K vacancy. To understand the influence of relaxations, we
      performed three levels of relaxations-only first nearest neighbors of the
      vacancy, first and second nearest neighbors, and full relaxation. Our
      calculations show that the relaxation significantly affects the energy surface
      and that the relaxation of the nearest neighbors to the vacancy accounts for most
      of the trend. The position of minimum energy for the Li was found to be along the
      [Formula: see text] direction. The calculated well along [Formula: see text] is
      102 meV deep relative to the on-center energy and lies about 0.86 A off-center.
      Minima along adjacent [Formula: see text] directions are separated by a saddle
      point barrier of 44 meV along the [Formula: see text] direction. Our calculated
      results are in agreement with prior model calculations and we believe our
      calculated potential surfaces are the best theoretical result so far.

PMID- 21715803
TI  - Solid-state amorphization of a quenched high-pressure GaSb phase studied by real
      time neutron diffraction: evolution of the crystalline phase.
AB  - The amorphization of a quenched sample of the GaSb-II high-pressure phase was
      studied at ambient pressure by real-time neutron diffraction in the course of the
      sample heating from 100 K to room temperature at a rate of 0.4 K min(-1). The
      transformation to the amorphous state begins at 140 K and is completed near room
      temperature. The beta-Sn type structure was shown to represent only the mean
      lattice of the high-pressure GaSb-II phase. The superstructure of this phase
      widely varied with temperature and is caused by the ordered displacement of
      atoms. The temperature range of the metastable crystalline phase relaxation is
      divided into three intervals according to the temperature dependence of the
      tetragonality ratio (c/a). At the boundaries of these temperature intervals, i.e.
      temperatures T = 170 and 230 K, two second-order phase transitions are observed.
      Anomalous heat and volumetric effects were observed earlier by means of
      calorimetry and dilatometry in the same temperature range. Variation of the beta
      Sn type crystal structure reflects the general tendency of ideal tetrahedral bond
      network recovery. All phase transformations observed were found to be
      irreversible.

PMID- 21715804
TI  - First-principles study of fission product (Xe, Cs, Sr) incorporation and
      segregation in alkaline earth metal oxides, HfO(2), and the MgO-HfO(2) interface.
AB  - In order to close the nuclear fuel cycle, advanced concepts for separating out
      fission products are necessary. One approach is to use a dispersion fuel form in
      which a fissile core is surrounded by an inert matrix that captures and
      immobilizes the fission products from the core. If this inert matrix can be
      easily separated from the fuel, via e.g. solution chemistry, the fission products
      can be separated from the fissile material. We examine a surrogate dispersion
      fuel composition, in which hafnia (HfO(2)) is a surrogate for the fissile core
      and alkaline earth metal oxides are used as the inert matrix. The questions of
      fission product incorporation in these oxides and possible segregation behavior
      at interfaces are considered. Density functional theory based calculations for
      fission product elements (Xe, Sr, and Cs) in these oxides are carried out. We
      find smaller incorporation energy in hafnia than in MgO for Cs and Sr, and Xe if
      variation of charge state is allowed. We also find that this trend is reversed or
      reduced for alkaline earth metal oxides with large cation sizes. Model
      interfacial calculations show a strong tendency of segregation from bulk MgO to
      MgO-HfO(2) interfaces.

PMID- 21715805
TI  - Steric effect on the M site of nanolaminate compounds M(2)SnC (M = Ti, Zr, Hf and
      Nb).
AB  - In this paper we report calculations based on an all electron ab initio full
      potential linearized augmented plane-wave method using the generalized gradient
      approximation within the density functional theory to determine the structures of
      Ti(2)SnC, Zr(2)SnC, Hf(2)SnC and Nb(2)SnC. The lattice constants obtained after
      geometry optimization are in good agreement with experimental data. It is
      observed from these results that there exists a steric effect on the M site. For
      M atoms with atomic radius (Zr, Hf) larger than that of tin, the polyhedra
      (octahedron and trigonal prism) constituting the unit cell are less distorted
      compared to those related to M atoms with atomic radius (Ti, Nb) similar to that
      of tin. The computed values for the bulk modulus of these ternary carbides are
      predicted to be about 69% of those of the corresponding binary carbides MC. The
      analysis of the projected local density of states shows that the major hybrids
      come from M (M = Ti, Zr, Hf, Nb) d and C p states.

PMID- 21715806
TI  - Iron dynamics in Al-Cu-Fe quasicrystals and approximants: Mossbauer and neutron
      experiments.
AB  - We present new results on the iron dynamics in the icosahedral quasicrystal i
      AlCuFe and two cubic approximants as well as the non-approximant Al-Cu-Fe cubic
      B2 phase. Conventional Mossbauer spectroscopy is used as well as, for the i
      AlCuFe phase, high Doppler velocity Mossbauer spectroscopy and quasielastic
      neutron scattering for samples with different Fe isotope contents. We show that
      in the i-phase the Fe Lamb-Mossbauer recoilless fraction decreases below that
      predicted for lattice vibrations alone for temperatures above about 550 K. This
      decrease is correlated with the onset of a quasielastic signal seen in both
      Mossbauer and neutron backscattering spectroscopy, which indicates the presence
      above 550 K of Fe jump processes confined in a local cage. The timescale of the
      Fe jumps (660 ps at 1000 K) and their temperature dependence differ widely from
      those of Cu jumps in the same i-AlCuFe quasicrystal. From the temperature
      dependence of the quadrupole splitting of the (57)Fe Mossbauer spectrum, one can
      distinguish two kinds of Fe jumps, one starting at 550 K and the second above 800
      K. In the two cubic approximants, a loss in the Fe recoilless fraction also
      occurs above 550 K, revealing the same kind of Fe dynamics as in the i-phase but
      the effect is smaller. On the other hand, no anomalous Fe dynamics (other than
      lattice vibrations) is detected in the B2-AlCuFe phase. Since the cubic
      approximants possess similar local configurations as the quasicrystal, we
      conclude that locally a Penrose tile description is appropriate. This shows that
      the detected Fe jumps can be interpreted in terms of phason-like local tiling
      flips.

PMID- 21715807
TI  - Structural stability and magnetic coupling in CaCu(3)Co(4)O(12) from first
      principles.
AB  - The structural, electronic and magnetic properties of CaCu(3)Co(4)O(12) were
      studied by use of the full-potential linearized augmented plane wave method. The
      calculated results indicate that CaCu(3)Co(4)O(12) is stable both
      thermodynamically and mechanically. Both GGA (generalized gradient approximation)
      and GGA+U methods predict that CaCu(3)Co(4)O(12) is metallic. The ferromagnetic
      configuration is only slightly more stable in energy compared with the non
      magnetic configuration (3.7 meV), suggesting that they are competitive for being
      the ground state. Co is in the low spin state (S = 1/2).

PMID- 21715808
TI  - A classical-map simulation of two-dimensional electron fluid: an extension of
      classical-map hypernetted-chain theory beyond the hypernetted-chain
      approximation.
AB  - A method for numerically simulating quantum systems is proposed and applied to
      the two-dimensional electron fluid at T = 0. This method maps quantum systems
      onto classical ones in the spirit of the classical-map hypernetted-chain theory
      and performs simulations on the latter. The results of the simulations are free
      from the assumption of the hypernetted-chain approximation and the neglect of the
      bridge diagrams. A merit of this method is the applicability to systems with
      geometrical complexity and finite sizes including the cases at finite
      temperatures. Monte Carlo and molecular dynamics simulations are performed
      corresponding to two previous proposals for the 'quantum' temperature and an
      improvement in the description of the diffraction effect. It is shown that one of
      these two proposals with the improved diffraction effect gives significantly
      better agreement with quantum Monte Carlo results reported previously for the
      range of 5<=r(s)<=40. These results may serve as the basis for the application of
      this method to finite non-periodic systems like quantum dots and systems at
      finite temperatures.

PMID- 21715809
TI  - Anomalies and Anderson localization: pi-coupling of the energy bands.
AB  - This work shows that delocalization phenomena in single-electron quasi-one
      dimensional quantum chains may occur at points different from the center of the
      energy spectrum (E = 0) and in systems lacking the symmetry [Formula: see text].
      It is found that the peaks appearing in the average conductance are controlled by
      the band structure of the periodic system underlying the disorder. The average
      conductance is expanded in powers of the disorder strength, allowing the
      conductance to be redefined as the sum of a regular and an anomalous
      contribution. The first non-vanishing term of the anomalous part is of the fourth
      order. The fourth-order term can be calculated for any number of coupled chains
      in terms of a matrix expression. For strictly one-dimensional systems the
      expansion is calculated up to the 12th order for both diagonal and real off
      diagonal disorder and is compared with the numerical data. It is also found that
      the anomalous contribution defined here is responsible for an even-odd effect of
      the average conductance.

PMID- 21715810
TI  - Geometrical phases of excitonic qubits in quantum dots.
AB  - We investigate the influence of phonon mediated interactions on the non-unitary
      evolution of geometrical phases in excitonic qubits formed in quantum dots
      entangled by pure Forster coupling. We consider decoherence to occur via acoustic
      phonons interacting through the deformation potential and piezoelectric coupling
      mechanisms. The influences of bath temperature, external electric field, quantum
      dot size and interdot distance on the evolution of geometrical phases are
      examined for the GaAs/AlGaAs material system. We extend the theory to determine
      the effect of dynamic decoupling employing ultrafast pi-pulses on the evolution
      of geometrical phases in the presence of dephasing processes.

PMID- 21715811
TI  - Exact solutions for a Dirac electron in an exponentially decaying magnetic field.
AB  - We consider a Dirac electron in the presence of an exponentially decaying
      magnetic field. We obtain exact energy eigenvalues with a zero-energy state and
      the corresponding eigenfunctions. We also calculate the probability density and
      current distributions.

PMID- 21715812
TI  - The effects of alloying elements Al and In on Ni-Mn-Ga shape memory alloys, from
      first principles.
AB  - The electronic structures and formation energies of the Ni(9)Mn(4)Ga(3-x)Al(x)
      and Ni(9)Mn(4)Ga(3-x)In(x) alloys have been investigated using the first
      principles pseudopotential plane-wave method based on density functional theory.
      The results show that both the austenite and martensite phases of Ni(9)Mn(4)Ga(3)
      alloy are stabilized by Al alloying, while they become unstable with In alloying.
      According to the partial density of states and structural energy analysis,
      different effects of Al and In alloying on the phase stability are mainly
      attributed to their chemical effects. The formation energy difference between the
      austenite and martensite phases decreases with Al or In alloying, correlating
      with the experimentally reported changes in martensitic transformation
      temperature. The shape factor plays an important role in the decrease of the
      formation energy difference.

PMID- 21715813
TI  - Electronic and magnetic properties of Mn-doped BeSiAs(2) and BeGeAs(2) compounds.
AB  - The structural, electronic and magnetic properties of BeSiAs(2) and BeGeAs(2)
      chalcopyrite ternary compounds doped with manganese were investigated by means of
      ab initio calculations. It was found that substitution of Be atoms by Mn
      increases the lattice constants of both compounds that provide acceptable
      mismatch with conventional Si, Ge and GaAs substrates. In spite of the increase
      of the spin polarization upon doping, both compounds possess antiferromagnetic
      (AFM) ordering with the impurity in the group II position whereas ferromagnetic
      (FM) ordering is obtained in the case of an impurity in the group IV position.

PMID- 21715814
TI  - The influence of hopping on modulated photoconductivity.
AB  - We have developed equations taking into account both multiple-trapping and
      hopping processes for describing transport phenomena in disordered
      semiconductors. These equations have been introduced into a numerical simulation
      to model the steady state dark conductivity and photoconductivity as well as the
      modulated photoconductivity. The influence of parameters such as the density of
      states and attempt-to-hop frequency on the results of these experiments has been
      investigated. Steady state and modulated photoconductivity experiments have been
      performed on a hydrogenated amorphous silicon film in the temperature range 18
      300 K and the results have been compared with those from the numerical
      simulation. This comparison shows that the latter provides a suitable
      interpretation of the experimental behaviours observed in both experiments.

PMID- 21715815
TI  - Effects of layered structural features on charge/orbital ordering in (La,
      Sr)(n+1)Mn(n)O(3n+1) (n = 1 and 2).
AB  - The charge/orbital ordering (COO) of the layered mixed-valence manganites
      (La,Sr)(n+1)Mn(n)O(3n+1) (n = 1 and 2) is examined by first-principles
      calculations and discussed in comparison with the La(0.5)Ca(0.5)MnO(3) perovskite
      phase ([Formula: see text]). The results demonstrated that the layered structural
      features could yield not only visibly weak coupling between Mn-O layers but also
      various features in the orbital ordering associated with different types of local
      structural distortions. In both La(0.5)Sr(1.5)MnO(4) (n = 1) and LaSr(2)Mn(2)O(7)
      (n = 2) phases, the orbital ordering can be chiefly assigned to the d(x(2)-y(2))
      orbital, in contrast with the zigzag-type d(z(2)) orbital ordering in the
      [Formula: see text] perovskite phase. Our theoretical analysis shows that a
      variety of essential factors, including the local structural distortions of the
      MnO(6) octahedra, the on-site Coulomb interaction, and magnetic interaction, have
      to be properly considered in order to achieve acceptable COO ground states for
      the layered variants in (La,Sr)(n+1)Mn(n)O(3n+1).

PMID- 21715816
TI  - Comparison of n-type Gd(2)O(3) and Gd-doped HfO(2).
AB  - Gd(2)O(3) and Gd-doped HfO(2) films were deposited on p-type silicon substrates
      in a reducing atmosphere. Gd 4f photoexcitation peaks at roughly 7 and 5 eV below
      the valence band maximum have been identified using the resonant photoemission of
      Gd(2)O(3) and Gd-doped HfO(2) films, respectively. In the case of Gd(2)O(3),
      strong hybridization with the O 2p band is demonstrated, and there is evidence
      that the Gd 4f weighted band exhibits dispersion in the bulk band structure. The
      rectifying (diode-like) properties of Gd-doped HfO(2)-silicon and Gd(2)O(3)
      silicon heterojunctions are demonstrated.

PMID- 21715817
TI  - Spectroscopic evidence of spinel phase clustering in solid solutions Hg(1
      x)Cr(x)Se (0.03 <= x <= 0.1).
AB  - The diluted magnetic semiconductors Hg(1-x)Cr(x)Se (0.03<=x<=0.1) were prepared
      by the solid state recrystallization method. The structure microanalysis of the
      Hg(1-x)Cr(x)Se compounds, performed by using a scanning electron spectrometer,
      has shown that the HgCr(2)Se(4) spinel-like inclusions are present in the host
      matrix Hg(1-x)Cr(x)Se and their amount increases when the chromium content grows.
      ESR studies of Hg(1-x)Cr(x)Se samples were carried out in the temperature range
      4.2-300 K. ESR spectra of the samples with different chromium contents
      demonstrate the same g-factors at room temperature and similar fine structure
      development with the temperature decrease. Numerical studies of g-factors,
      performed by the modified crystal field approach (MCFA), allowed us to reveal
      that Cr(2+)/Cr(3+) ions in the tetrahedral environment of the solid solution Hg(1
      x)Cr(x)Se cannot lead to the ESR signal. The experimental g-factor is well
      reproduced by a numerical g-factor for Cr(3+) ions located in the octahedral
      environment, being specific for the HgCr(2)Se(4) spinel phase. The onset of the
      ESR fine structure is determined by the trigonal distortions of the (CrSe(6))(9-)
      octahedral cell. From our study it has been found that the spinel clusters are
      present in the Hg(1-x)Cr(x)Se solid solution even at low chromium content.

PMID- 21715818
TI  - Self-interaction correction in multiple scattering theory: application to
      transition metal oxides.
AB  - We apply to transition metal monoxides the self-interaction corrected (SIC) local
      spin density approximation, implemented locally in the multiple scattering theory
      within the Korringa-Kohn-Rostoker (KKR) band structure method. The calculated
      electronic structure and in particular magnetic moments and energy gaps are
      discussed in reference to the earlier SIC results obtained within the linear
      muffin-tin orbital atomic sphere approximation band structure method, involving
      transformations between Bloch and Wannier representations, in order to solve the
      eigenvalue problem and calculate the SIC charge and potential. Since the KKR
      method can be easily extended to treat disordered alloys, by invoking the
      coherent potential approximation (CPA), in this paper we compare the CPA approach
      and supercell calculations to study the electronic structure of NiO with cation
      vacancies.

PMID- 21715819
TI  - Implementation of adiabatic geometric gates with superconducting phase qubits.
AB  - We present an adiabatic geometric quantum computation strategy based on the non
      degenerate energy eigenstates in (but not limited to) superconducting phase qubit
      systems. The fidelity of the designed quantum gate was evaluated in the presence
      of simulated thermal fluctuations in a superconducting phase qubits circuit and
      was found to be quite robust against random errors. In addition, it was
      elucidated that the Berry phase in the designed adiabatic evolution may be
      detected directly via the quantum state tomography developed for superconducting
      qubits. We also analyze the effects of control parameter fluctuations on the
      experimental detection of the Berry phase.

PMID- 21715820
TI  - Non-volatile resistive switching in the dielectric superconductor YBa(2)Cu(3)O(7
      delta).
AB  - We report on the reversible, non-volatile and polarity-dependent resistive
      switching between superconductor and insulator states at the interfaces of an
      Au/YBa(2)Cu(3)O(7-delta) (YBCO)/Au system. We show that, upon application of
      electric pulses, the superconducting state of YBCO in regions near the electrodes
      can be reversibly removed and restored. In addition, four-wire measurements
      reveal that pulsing also induces significant non-volatile changes in the bulk
      resistance. We argue that our observations are compatible with a scenario where
      the switching effect is due to migration of oxygen ions along grain boundaries
      that control the inter-grain superconducting coupling.

PMID- 21715821
TI  - Ising t-J model close to half filling: a Monte Carlo study.
AB  - Within the recently proposed doped-carrier representation of the projected
      lattice electron operators we derive a full Ising version of the t-J model. This
      model possesses the global discrete Z(2) symmetry as a maximal spin symmetry of
      the Hamiltonian at any values of the coupling constants, t and J. In contrast, in
      the spin anisotropic limit of the t-J model, usually referred to as the t-J(z)
      model, the global SU(2) invariance is fully restored at J(z) = 0, so that only
      the spin-spin interaction has in this model the true Ising form. We discuss a
      relationship between these two models and the standard isotropic t-J model. We
      show that the low-energy quasiparticles in all three models share qualitatively
      similar properties at low doping and small values of J/t. The main advantage of
      the proposed Ising t-J model over the t-J(z) one is that the former allows for
      the unbiased Monte Carlo calculations on large clusters of up to 10(3) sites.
      Within this model we discuss in detail the destruction of the antiferromagnetic
      (AF) order by doping as well as the interplay between the AF order and hole
      mobility. We also discuss the effect of the exchange interaction and that of the
      next-nearest-neighbour hoppings on the destruction of the AF order at finite
      doping. We show that the short-range AF order is observed in a wide range of
      temperatures and dopings, much beyond the boundaries of the AF phase. We
      explicitly demonstrate that the local no-double-occupancy constraint plays the
      dominant role in destroying the magnetic order at finite doping. Finally, a role
      of inhomogeneities is discussed.

PMID- 21715822
TI  - A new behaviour of ac losses in superconducting Bi(2)Sr(2)CaCu(2)O(8) single
      crystals.
AB  - A new ac loss behaviour is observed in the superconducting state of
      Bi(2)Sr(2)CaCu(2)O(8) single crystals using a novel technique of measuring
      dissipation at radio frequencies. It is found that the ac loss in the
      superconducting state is larger than that in the normal state. This counter
      intuitive result is explained in terms of the cumulative effect of repetitive
      decoupling of intrinsic Josephson junctions in the crystals and analysed in the
      framework of Ambegaokar-Baratoff theory. The ac losses are studied as a function
      of temperature, rf amplitude and magnetic field applied at different
      orientations. A peak in ac losses is observed in the superconducting state along
      the temperature scale. The amplitude of the peak decreases and shifts towards
      lower temperature with increasing field and also when the field orientation with
      respect to the c axis of the crystal changes from the perpendicular to parallel
      direction. The origin of the peak and its behaviour are discussed in the context
      of coupling energy of Josephson junctions present in the sample. In the presence
      of a magnetic field another peak in ac losses arises at temperatures close to
      T(c), which is associated with the Lorentz-force-driven motion of vortices.

PMID- 21715823
TI  - Characterization of defect levels in semi-insulating 6H-SiC by means of
      photoinduced transient spectroscopy and modulated photocurrent technique.
AB  - Parameters of electrically active defect centres in vanadium-doped 6H silicon
      carbide (6H-SiC:V) were investigated by means of the photoinduced transient
      spectroscopy (PITS) and modulated photocurrent (MPC) method. After a short
      description of the two techniques, experimental results are presented and briefly
      compared. Our aim is mainly to understand and explain these experimental results.
      In particular, in the PITS technique a shallow level seems to be at the origin of
      negative photoconductivity. Besides, in the same temperature range hole and
      electron levels can be detected at the same time. Finally, the detection of a
      given level seems to depend on the photon flux used to perform the PITS
      experiment. As far as the MPC experiment is concerned, it has put into evidence a
      very efficient shallow level. A numerical calculation was developed to simulate
      both experiments in order to understand the experimental results. By means of
      this simulation, we have explained all the phenomena observed experimentally in
      each technique and we propose a simple model for the distribution of electrically
      active defect centres in 6H-SiC:V crystals.

PMID- 21715824
TI  - Optical electron spin pumping in n-doped quantum wells.
AB  - A theoretical model for optical spin pumping of electrons in a quantum well with
      low intrinsic electron density is presented. A system of electrons under
      continuous-wave illumination by circularly polarized light tuned to the electron
      trion resonance is considered. The simultaneous off-resonant creation of excitons
      is also taken into account. The spin flip of trions and their radiative decay as
      the basic processes which allow the electronic spin pumping, as well as other
      processes, such as the formation of trions from excitons and electrons, are
      accounted for in the appropriate kinetic equations. The results obtained for CdTe
      and GaAs quantum wells indicate that significant electron spin polarization can
      be achieved in a time range of a few nanoseconds.

PMID- 21715825
TI  - Improvement of the photon generation efficiency in phosphorus-doped silicon
      nanocrystals: Gamma-X mixing of the confined electron states.
AB  - It has been shown that the central-cell potential of a phosphorus ion embedded in
      a silicon nanocrystal effectively mixes the electronic states of X- and Gamma
      bands. Quantum confinement strengthens the Gamma-X mixing which, in turn,
      straightens the nanocrystal's band structure, and substantially intensifies
      interband radiative recombination.

PMID- 21715826
TI  - Thermal transport across incommensurate phases in potassium selenate: photo
      pyroelectric and calorimetric measurements.
AB  - The thermal transport properties-thermal diffusivity, thermal conductivity and
      specific heat capacity-of potassium selenate crystal have been measured through
      the successive phase transitions, following the photo-pyroelectric thermal wave
      technique. The variation of thermal conductivity with temperature through the
      incommensurate (IC) phase of this crystal is measured. The enhancement in thermal
      conductivity in the IC phase is explained in terms of heat conduction by phase
      modes, and the maxima in thermal conductivity during transitions is due to
      enhancement in the phonon mean free path and the corresponding reduction in
      phonon scattering. The anisotropy in thermal conductivity and its variation with
      temperature are reported. The variation of the specific heat with temperature
      through the high temperature structural transition at 745 K is measured,
      following the differential scanning calorimetric method. By combining the results
      of photo-pyroelectric thermal wave methods and differential scanning calorimetry,
      the variation of the specific heat capacity with temperature through all the four
      phases of K(2)SeO(4) is reported. The results are discussed in terms of phonon
      mode softening during transitions and phonon scattering by phase modes in the IC
      phase.

PMID- 21715827
TI  - (39)K NMR and EPR study of multiferroic K(3)Fe(5)F(15).
AB  - (39)K NMR spectra and relaxation times of polycrystalline K(3)Fe(5)F(15) have
      been used as a microscopic detector of the local magnetic fields at the magnetic
      transition at T(N) = 123 K. The NMR lineshape widens abruptly upon crossing T(N)
      due to the onset of internal magnetic fields, while we find no significant
      lineshift. The paraelectric to ferroelectric transition at T(c) = 490 K and the
      magnetic transition at T(N) have also been studied using X-band EPR (electron
      paramagnetic resonance). An increase and subsequent decrease in the EPR
      susceptibilities is observed on approaching T(N) from above. There is also a
      significant increase in the linewidth. At the same time the g-factor first
      decreases and then increases with decreasing temperature. The local magnetic
      field is different at different K sites and is much smaller than the magnetic
      field around the Fe sites. This seems to be consistent with the behaviour of a
      weak ferrimagnet. The ferrimagnetism does not seem to be due to spin canting as
      the lattice is disordered, but may arise from thermal blocking of
      superparamagnetic percolation clusters. The ferroelectric transition at T(c)
      shows no electronic anomaly, demonstrating that we are dealing with a classical
      phonon anomaly as found in conventional oxides rather than an electronic
      transition.

PMID- 21715828
TI  - Magneto-elastic phase transitions in one-dimensional systems.
AB  - The magneto-elastic phase diagram in one-dimensional systems relating to the
      interplay between magnetism and lattice distortion is studied in a double
      exchange and super-exchange model considering classical localized spins and the
      limit of large Hund's coupling. At low super-exchange interaction energy, a phase
      transition occurs between electron-full ferromagnetic distorted and electron
      empty antiferromagnetic undistorted phases via phase separation. In this case,
      all electrons and lattice distortions are found within the ferromagnetic domain.
      For higher super-exchange interaction energy, phase separations consisting of two
      or three-site distorted independent magnetic polarons separated by electron
      empty undistorted antiferromagnetic links are obtained. In this regime, each
      polaron contains an electron, leading to a Wigner crystallization. The lattice
      distortion and charge distribution inside the polarons are also calculated.

PMID- 21715829
TI  - Electron spin resonance study of polycrystalline La(0.75)(Ca(x)Sr(1
      x))(0.25)MnO(3) (x = 0, 0.45, 1).
AB  - Electron spin resonance (ESR) spectra of polycrystalline La(0.75)(Ca(x)Sr(1
      x))(0.25)MnO(3) (x = 0, 0.45, 1) were studied within the temperature range 110
      K<=T<=470 K. The temperature dependence of the ESR intensity for the samples is
      described by a thermally activated model in the paramagnetic regime. It is found
      that the activation energy in the orthorhombic phase is higher than that in the
      rhombohedral phase for La(0.75)(Ca(0.45)Sr(0.55))(0.25)MnO(3). It is suggested
      that a higher energy is required to destroy the correlated polarons due to the
      fact that correlated polarons only exist in the orthorhombic phase. This
      proposition is confirmed by the analysis of the ESR linewidth data, which can be
      well fitted by the model of adiabatic hopping motion of small polarons. In
      addition, it is found that, at a fixed temperature, the linewidth decreases with
      increasing Sr doping, which reveals that the structural tolerance factor has a
      significant effect on the linewidth.

PMID- 21715830
TI  - Superferromagnetism in mechanically alloyed fcc Fe(23)Cu(77) with bimodal cluster
      size distribution.
AB  - Magnetic measurements, x-ray diffraction and Mossbauer spectroscopy were used to
      characterize a nanostructured fcc Fe(23)Cu(77) at.% alloy prepared by high-energy
      ball-milling, addressing in particular the effect of clustering on the nature of
      the interacting magnetic entities. The interpretation of magnetization
      measurements leads to the conclusion that grains, whose mean size is ~16 nm,
      contain two populations of magnetic Fe-rich nanoclusters with a bimodal size
      distribution. These two sets of clusters contain about 14 and 400 Fe atoms and
      have magnetic moments of 30 u(B) and 860 u(B), respectively. The inter-cluster
      ferromagnetic interactions that lead to superferromagnetism with a Curie
      temperature T(C)~220 K can be described by a mean field determined by the smaller
      clusters only, which account for 90% of the magnetization.

PMID- 21715831
TI  - Study of the size-dependent properties of Sc(n)Al (n = 1-14) clusters by density
      functional theory.
AB  - The geometries, stabilities, and electronic and magnetic properties of Sc(n)Al (n
      = 1-14) clusters with different spin configurations have been investigated
      systematically within the framework of the gradient-corrected density-functional
      theory. Our resulting geometries show that the aluminum atom remains on the
      surface of clusters with n<9, while it takes up the center of Sc-cage clusters
      with n>=9. Besides, the doping of Al improves the stability of the host clusters.
      Maximum peaks are observed for Sc(n)Al clusters at n = 3, 6, 10 and 12 with the
      size dependent on the second-order energy differences and fragmentation energies,
      implying that these clusters are relatively more stable. For all the Sc(n)Al
      clusters studied, we find the charge transfer from Sc to Al sites and the
      coexistence of ionic and covalent bonding characteristics. The doping of the Al
      atom induces the magnetic moments of the host clusters decrease except for n = 8
      and 14 and the total magnetic moments are quenched at n = 5, 7, 9 and 11.

PMID- 21715832
TI  - Tunnel magnetoresistance for coherent spin-flip processes on an interacting
      quantum dot.
AB  - Spin-polarized electronic tunneling through a quantum dot coupled to
      ferromagnetic electrodes is investigated within a nonequilibrium Green function
      approach. An interplay between coherent intradot spin-flip transitions, tunneling
      processes and Coulomb correlations on the dot is studied for current-voltage
      characteristics of the tunneling junction in parallel and antiparallel magnetic
      configurations of the leads. It is found that due to the spin-flip processes
      electric current in the antiparallel configuration tends to the current
      characteristics in the parallel configuration, thus giving rise to suppression of
      the tunnel magnetoresistance (TMR) between the threshold bias voltages at which
      the dot energy level becomes active in tunneling. Also, the effect of a negative
      differential conductance in symmetrical junctions, splitting of the conductance
      peaks, significant modulation of TMR peaks around the threshold bias voltages as
      well as suppression of the diode-like behavior in asymmetrical junctions is
      discussed in the context of coherent intradot spin-flip transitions. It is also
      shown that TMR may be inverted at selected gate voltages, which qualitatively
      reproduces the TMR behavior predicted recently for temperatures in the Kondo
      regime, and observed experimentally beyond the Kondo regime for a semiconductor
      InAs quantum dot coupled to nickel electrodes.

PMID- 21715833
TI  - Magnetic and neutron diffraction study on quaternary oxides MTeMoO(6) (M = Mn and
      Zn).
AB  - Crystal structures and magnetic properties of quaternary oxides MTeMoO(6) (M = Mn
      and Zn) were investigated. From the Rietveld analyses for the powder x-ray and
      neutron diffraction measurements, their detailed structures have been determined.
      Both compounds have orthorhombic structure with space group P 2(1)2(1)2 and a
      charge configuration of M(2+)Te(4+)Mo(6+)O(6). ZnTeMoO(6) shows diamagnetic
      behavior. In this structure, M ions are arranged in a square-planar manner. The
      temperature dependence of the magnetic susceptibility for MnTeMoO(6) shows a
      broad peak at ~33 K, which is due to a two-dimensional characteristic of the
      magnetic interaction. In addition, this compound shows an antiferromagnetic
      transition at 20 K. The magnetic structure was determined by the powder neutron
      diffraction measurement at 3.3 K. The magnetic moments of Mn(2+) ions (4.45
      MU(B)) order in a collinear antiferromagnetic arrangement along the b axis.

PMID- 21715834
TI  - Dilution and non-Fermi-liquid effects in the CePtIn Kondo lattice.
AB  - Measurements of electrical resistivity (rho(T)), magnetoresistivity (MR),
      magnetic susceptibility (chi(T)) and heat capacity (C(P)(T)) are presented for
      the (Ce(1-x)La(x))PtIn alloy system of which the CePtIn parent is a known dense
      Kondo compound that does not order magnetically down to 50 mK. chi(T) for alloys
      0<=x<=0.8 exhibits Curie-Weiss behaviour. rho(T) results indicate a transition
      from a dense Kondo behaviour for 0<=x<=0.2 to a single-ion Kondo region
      (0.3<=x<=0.8). The Kondo energy scale as given by T(K) values calculated from MR
      studies and by the temperature T(max)(rho(mag)) where the magnetic contribution
      to rho(T) exhibits a maximum value, is compared with theoretical models. It is
      shown that the experimental results not only depend on a volume effect as given
      by the compressible Kondo lattice model of Lavagna but in addition confirm the
      more complex behaviour recently presented by Burdin and Fulde for a Kondo alloy
      system in which the magnetic (Ce) and non-magnetic (La) atoms are distributed
      randomly. Non-Fermi-liquid behaviour is predicted by Burdin and Fulde at certain
      critical concentrations of the alloy system and experimental evidence for this is
      presented through chi(T), rho(T) and C(P)(T) measurements.

PMID- 21715835
TI  - Molecular dewetting on insulators.
AB  - Recent attention given to the growth and morphology of organic thin films with
      regard to organic electronics has led to the observation of dewetting (a
      transition from layer(s) to islands) of molecular deposits in many of these
      systems. Dewetting is a much studied phenomenon in the formation of polymer and
      liquid films, but its observation in thin films of the 'small' molecules typical
      of organic electronics requires additional consideration of the structure of the
      interface between the molecular film and the substrate. This review covers some
      key concepts related to dewetting and molecular film growth. In particular, the
      origins of different growth modes and the thickness dependent interactions which
      give rise to dewetting are discussed in terms of surface energies and the
      disjoining pressure. Characteristics of molecular systems which may lead to these
      conditions, including the formation of metastable interface structures and
      commensurate-incommensurate phase transitions, are also discussed. Brief
      descriptions of some experimental techniques which have been used to study
      molecular dewetting are given as well. Examples of molecule-on-insulator systems
      which undergo dewetting are described in some detail, specifically perylene
      derivatives on alkali halides, C(60) on alkali halides, and the technologically
      important system of pentacene on SiO(2). These examples point to some possible
      predicting factors for the occurrence of dewetting, most importantly the
      formation of an interface layer which differs from the bulk crystal structure.

PMID- 21715836
TI  - Intricate coupling between ion-ion and ion-surface correlations in double layers
      as illustrated by charge inversion-combined effects of strong Coulomb
      correlations and excluded volume.
AB  - Many-body correlations in electrolyte systems are important when the
      electrostatic coupling and/or the volume fraction of ions are not low. Such
      correlations are ignored in the traditional theories of electrolytes based on the
      Poisson-Boltzmann approximation. In the general case, the ion density profiles
      (ion-surface correlation functions) and the ion-ion correlation functions in
      diffuse electric double layers are strongly interdependent. Both have to be
      included in the treatment of the system to capture many essential properties. In
      this work the coupling between the ion-ion and ion-surface correlations and
      effects of this coupling are illustrated explicitly and graphically (visually).
      The average forces that act on the ions in the double layer are analysed. This
      leads to an understanding of mechanisms in action in the inhomogeneous
      electrolyte near a surface. Charge separation in an electrolyte outside an
      uncharged surface and charge inversion of highly charged surfaces are thereby
      used as examples of what insights can be gained by this kind of approach. Some
      links to mechanisms behind like-charge attraction are also discussed.

PMID- 21715837
TI  - Inflation of the screening length induced by Bjerrum pairs.
AB  - Within a modified Poisson-Boltzmann theory we study the effect of Bjerrum pairs
      on the typical length scale [Formula: see text] over which electric fields are
      screened in electrolyte solutions, taking into account a simple association
      dissociation equilibrium between free ions and Bjerrum pairs. At low densities of
      Bjerrum pairs, this length scale is well approximated by the Debye length
      [Formula: see text], with rho(s) the free-ion density. At high densities of
      Bjerrum pairs, however, we find [Formula: see text], which is significantly
      larger than 1/kappa due to the enhanced effective permittivity of the
      electrolyte, caused by the polarization of Bjerrum pairs. We argue that this
      mechanism may explain the recently observed anomalously large colloid-free zones
      between an oil-dispersed colloidal crystal and a colloidal monolayer at the oil
      water interface.

PMID- 21715838
TI  - The role of multipoles in counterion-mediated interactions between charged
      surfaces: strong and weak coupling.
AB  - We present general arguments for the importance, or lack thereof, of structure in
      the charge distribution of counterions for counterion-mediated interactions
      between bounding symmetrically charged surfaces. We show that on the mean field
      or weak coupling level, the charge quadrupole contributes the lowest order
      modification to the contact value theorem and thus to the intersurface
      electrostatic interactions. The image effects are non-existent on the mean field
      level even with multipoles. On the strong coupling level the quadrupoles and
      higher order multipoles contribute additional terms to the interaction free
      energy only in the presence of dielectric inhomogeneities. Without them, the
      monopole is the only multipole that contributes to the strong coupling
      electrostatics. We explore the consequences of these statements in all their
      generality.

PMID- 21715839
TI  - Non-mean-field screening by multivalent counterions.
AB  - Screening of a strongly charged macroion by its multivalent counterions cannot be
      described in the framework of a mean-field Poisson-Boltzmann (PB) theory because
      multivalent counterions form a strongly correlated liquid (SCL) on the surface of
      the macroion. It was predicted that a distant counterion polarizes the SCL as if
      it were a metallic surface and creates an electrostatic image. The attractive
      potential energy of the image is the reason why the charge density of counterions
      decreases faster with distance from the charged surface than in PB theory. Using
      the Monte Carlo method to find the equilibrium distribution of counterions around
      the macroion, we confirm the existence of the image potential energy. It is also
      shown that, due to the negative screening length of the SCL, -2xi, the effective
      metallic surface is actually above the SCL by |xi|.

PMID- 21715840
TI  - Additional considerations about the role of ion size in charge reversal.
AB  - The effect of the ion size on the charge reversal process is studied via
      canonical Monte Carlo simulation. To this end, a primitive model of electrolyte
      is used to analyze the electric double layer formed by an asymmetric electrolyte
      in the presence of a charged planar wall. Different values of ion diameters and
      surface charge densities are used so as to determine the conditions at which the
      charge reversal first occurs. For each case, the apparent surface charge density
      is calculated as a function of the distance from the charged wall for the
      different electrolyte concentrations in order to establish the minimal salt
      concentration required for the charge reversal. We will refer to this electrolyte
      concentration as the reversal concentration and will show how it depends on the
      surface charge density and on the ion size. From the apparent surface charge
      density profiles, the distance from the wall at which the charge reversal arises
      as well as its intensity can be also inferred.

PMID- 21715841
TI  - Beyond standard Poisson-Boltzmann theory: ion-specific interactions in aqueous
      solutions.
AB  - The Poisson-Boltzmann mean-field description of ionic solutions has been
      successfully used in predicting charge distributions and interactions between
      charged macromolecules. While the electrostatic model of charged fluids, on which
      the Poisson-Boltzmann description rests, and its statistical mechanical
      consequences have been scrutinized in great detail, much less is understood about
      its probable shortcomings when dealing with various aspects of real physical,
      chemical and biological systems. These shortcomings are not only a consequence of
      the limitations of the mean-field approximation per se, but perhaps are primarily
      due to the fact that the purely Coulombic model Hamiltonian does not take into
      account various additional interactions that are not electrostatic in their
      origin. We explore several possible non-electrostatic contributions to the free
      energy of ions in confined aqueous solutions and investigate their ramifications
      and consequences on ionic profiles and interactions between charged surfaces and
      macromolecules.

PMID- 21715842
TI  - Stability mechanisms for plate-like nanoparticles immersed in a macroion
      dispersion.
AB  - An integral equation theory and Monte Carlo simulations are applied to study a
      model macroion solution confined between two parallel plates immersed in a 1:1
      electrolyte and the macroions' counterions. We analyze the cases in which plates
      are: (a) uncharged; (b) when they are like-charged to the macroions; (c) when
      they are oppositely charged to the macroions. For all cases a long range
      oscillatory behavior of the induced charge density between the plates is found
      (implying an overcompensation/undercompensation of the plates' charge density)
      and a correlation between the confined and outside fluids. The behavior of the
      force is discussed in terms of the macroion and ion structure inside and outside
      the plates. A good agreement is found between theoretical and simulation results.

PMID- 21715843
TI  - Ion specific correlations in bulk and at biointerfaces.
AB  - Ion specific effects are ubiquitous in any complex colloidal or biological fluid
      in bulk or at interfaces. The molecular origins of these 'Hofmeister effects' are
      not well understood and their theoretical description poses a formidable
      challenge to the modeling and simulation community. On the basis of the
      combination of atomistically resolved molecular dynamics (MD) computer
      simulations and statistical mechanics approaches, we present a few selected
      examples of specific electrolyte effects in bulk, at simple neutral and charged
      interfaces, and on a short alpha-helical peptide. The structural complexity in
      these strongly Coulomb-correlated systems is highlighted and analyzed in the
      light of available experimental data. While in general the comparison of MD
      simulations to experiments often lacks quantitative agreement, mostly because
      molecular force fields and coarse-graining procedures remain to be optimized, the
      consensus as regards trends provides important insights into microscopic
      hydration and binding mechanisms.

PMID- 21715844
TI  - Ion adsorption at a metallic electrode: an ab initio based simulation study.
AB  - A method for parametrizing, from first principles density functional theory
      calculations, a model of the interactions between the ions in an ionic liquid and
      a metallic (electrode) surface is described. The interaction model includes the
      induction of dipoles on the ions of the liquid by their mutual interaction and
      the interaction with the electrode surface as well as the polarization of the
      metal by the ionic charges and dipoles ('image' interactions). The method is used
      to obtain a suitable interaction model for a system consisting of a LiCl liquid
      electrolyte and a solid aluminium electrode. The model is then used in
      simulations of this system for various values of the electrical potential applied
      to the electrode. The evolution of the liquid structure at the electrochemical
      interface with applied potential is followed and the capacitance of the
      electrochemical interface is measured. The electrolyte is found to exhibit a
      potential-driven phase transition which involves the commensurate ordering of the
      electrolyte ions with the electrode surface; this leads to a maximum in the
      differential capacitance as a function of applied potential. Away from the phase
      transition the capacitance was found to be independent of the applied potential.

PMID- 21715845
TI  - Multilayered crystals of macroions under slit confinement.
AB  - The crystalline ground state of macroions confined between two neutral parallel
      plates in the presence of their homogeneously spread counterions is calculated by
      lattice sum minimization of candidate phases involving up to six layers. For
      increasing macroion density, a cascade of solid-solid transitions is found
      involving various multilayered crystals. The cascade includes triangular
      monolayer and buckled bilayer as well as rhombic, squared and triangular phase
      structures.

PMID- 21715846
TI  - Salt-induced aggregation of stiff polyelectrolytes.
AB  - Molecular dynamics simulation techniques are used to study the process of
      aggregation of highly charged stiff polyelectrolytes due to the presence of
      multivalent salt. The dominant kinetic mode of aggregation is found to be the
      case of one end of one polyelectrolyte meeting others at right angles, and the
      kinetic pathway to bundle formation is found to be similar to that of
      flocculation dynamics of colloids as described by Smoluchowski. The aggregation
      process is found to favor the formation of finite bundles of 10-11 filaments at
      long times. Comparing the distribution of the cluster sizes with the Smoluchowski
      formula suggests that the energy barrier for the aggregation process is
      negligible. Also, the formation of long-lived metastable structures with
      similarities to the raft-like structures of actin filaments is observed within a
      range of salt concentration.

PMID- 21715847
TI  - Swelling of biological and semiflexible polyelectrolytes.
AB  - We have developed a theoretical model of swelling of semiflexible (biological)
      polyelectrolytes in salt solutions. Our approach is based on separation of length
      scales which allowed us to split a chain's electrostatic energy into two parts
      that describe local and remote electrostatic interactions along the polymer
      backbone. The local part takes into account interactions between charged monomers
      that are separated by distances along the polymer backbone shorter than the
      chain's persistence length. These electrostatic interactions renormalize chain
      persistence length. The second part includes electrostatic interactions between
      remote charged pairs along the polymer backbone located at distances larger than
      the chain persistence length. These interactions are responsible for chain
      swelling. In the framework of this approach we calculated effective chain
      persistence length and chain size as a function of the Debye screening length,
      chain degree of ionization, bare persistence length and chain degree of
      polymerization. Our crossover expression for the effective chain's persistence
      length is in good quantitative agreement with the experimental data on DNA. We
      have been able to fit experimental datasets by using two adjustable parameters:
      DNA ionization degree (alpha = 0.15-0.17) and a bare persistence length (l(p) =
      40-44 nm).

PMID- 21715848
TI  - Charge correlation effects on ionization of weak polyelectrolytes.
AB  - Ionization curves of weak polyelectrolytes were obtained as a function of the
      charge coupling strength from Monte Carlo simulations. In contrast to many
      earlier studies, the present work treats counterions explicitly, thus allowing
      the investigation of charge correlation effects at strong couplings. For
      conditions representing typical weak polyelectrolytes in water near room
      temperature, ionization is suppressed because of interactions between nearby
      dissociated groups, as also seen in prior work. A novel finding here is that, for
      stronger couplings, relevant for non-aqueous environments in the absence of added
      salt, the opposite behavior is observed-ionization is enhanced relative to the
      behavior of the isolated groups due to ion-counterion correlation effects. The
      fraction of dissociated groups as a function of position along the chain also
      behaves non-monotonically. Dissociation is highest near the ends of the chains
      for aqueous polyelectrolytes and highest at the chain middle segments for non
      aqueous environments. At intermediate coupling strengths, dissociable groups
      appear to behave in a nearly ideal fashion, even though chain dimensions still
      show strong expansion effects due to ionization. These findings provide physical
      insights on the impact of competition between acid/base chemical equilibrium and
      electrostatic attractions in ionizable systems.

PMID- 21715849
TI  - Surface patterning of low-dimensional systems: the chirality of charged fibres.
AB  - Charged surfaces are interesting for their ability to have long-range
      correlations and their ability to be dynamically tuned. While the configurations
      of charged planar surfaces have been thoroughly mapped and studied, charged
      cylindrical surfaces show novel features. The surface patterning of cylindrically
      confined charges is discussed with emphasis on the role of chiral configurations.
      The origins of surface patterns due to competing interactions in charged
      monolayers are summarized along with their associated theoretical models. The
      electrostatically induced patterns described in this paper are important in many
      low-dimensional biological systems such as plasma membrane organization,
      filamentous virus capsid structure or microtubule interactions. A simple model
      effectively predicting some features of chiral patterns in biological systems is
      presented. We extend our model from helical lamellar patterns to elliptical
      patterns to consider asymmetrical patterns in assemblies of filamentous
      aggregates.

PMID- 21715850
TI  - Hydration structures near finite-sized nanoscopic objects reconstructed using
      inelastic x-ray scattering measurements.
AB  - Recent work has shown that it is possible to use high resolution dynamical
      structure factor S(q,omega) data measured with inelastic x-ray scattering to
      reconstruct the Green's function of water, which describes its dynamical density
      response to a point charge. Here, we generalize this approach and describe a
      strategy for reconstructing hydration behavior near simple charge distributions
      with excluded volumes, with the long term goal of engaging hydration processes in
      complex molecular systems. We use this Green's function based imaging of dynamics
      method to generate hydration structures and show that they are consistent with
      those of well-studied model systems.

PMID- 21715851
TI  - Dynamics of binary mixtures with ions: dynamic structure factor and mesophase
      formation.
AB  - Dynamic equations are presented for polar binary mixtures containing ions in the
      presence of preferential solvation. In one-phase states, we calculate the dynamic
      structure factor of the composition accounting for ion motion. Microphase
      separation can take place for sufficiently large solvation asymmetry of the
      cations and the anions. We show two-dimensional simulation results of the
      mesophase formation with an antagonistic salt, where the cations are hydrophilic
      and the anions are hydrophobic. The structure factor S(q) in the resultant
      mesophase has a sharp peak at an intermediate wavenumber of the order of the
      Debye-Huckel wavenumber. As the quench depth is increased, the surface tension
      nearly vanishes in mesophases due to an electric double layer.

PMID- 21715852
TI  - Nonadditivity in the effective interactions of binary charged colloidal
      suspensions.
AB  - Based on primitive model computer simulations with explicit microions, we
      calculate the effective interactions in a binary mixture of charged colloids with
      species A and B for different size and charge ratios. An optimal pairwise
      interaction is obtained by fitting the many-body effective forces. This
      interaction is close to a Yukawa (or Derjaguin-Landau-Verwey-Overbeek (DLVO))
      pair potential but the AB cross-interaction is different from the geometric mean
      of the two direct AA and BB interactions. As a function of charge asymmetry, the
      corresponding nonadditivity parameter is first positive, then significantly
      negative and is then positive again. We finally show that an inclusion of
      nonadditivity within an optimal effective Yukawa model gives better predictions
      for the fluid pair structure than DLVO theory.

PMID- 21715853
TI  - Nanometric ionic-liquid films on silica: a joint experimental and computational
      study.
AB  - Atomic force microscopy images for [bmim][Tf(2)N] films deposited at ambient
      conditions by drop-casting show a population of terraced islands of mesoscopic
      area (1-100 MU(2)) and ~50 nm height. The regularity of terraces and steps, stiff
      mechanical properties and a fragile fracture mode all suggest that the islands
      are solid-like, even though bulk [bmim][Tf(2)N] is liquid at the temperature of
      the experiment. Molecular dynamics simulations for a homogeneous [bmim][Tf(2)N]
      film 4 nm thick on silica also display marked layering in proximity to silica of
      periodicity closely matching the experimental estimate of the step height. The
      density modulation of the simulated sample, however, decays into an
      approximatively homogeneous and fluid-like density distribution ~2 nm from the
      solid surface. The detailed comparison of experiments and simulations is
      contained in the closing section of the paper.

PMID- 21715854
TI  - Liquid-liquid phase separation in solutions of ionic liquids: phase diagrams,
      corresponding state analysis and comparison with simulations of the primitive
      model.
AB  - Phase diagrams of ionic solutions of the ionic liquid C(18)mim(+)NTF(2)(-) (1-n
      octadecyl-3-methyl imidazolium bistrifluormethylsulfonylimide) in decalin,
      cyclohexane and methylcyclohexane are reported and compared with that of
      solutions of other imidazolium ionic liquids with the anions NTF(2)(-), Cl(-) and
      BF4(-) in arenes, CCl(4), alcohols and water. The phase diagrams are analysed
      presuming Ising criticality and taking into account the asymmetry of the phase
      diagrams. The resulting parameters are compared with simulation results for equal
      sized charged hard spheres in a dielectric continuum, the restricted primitive
      model (RPM) and the primitive model (PM) that allows for ions of different size.
      In the RPM temperature scale the critical temperatures vary almost linearly with
      the dielectric permittivity of the solvent. The RPM critical temperatures of the
      solutions in non-polar solvents are very similar, somewhat below the RPM value.
      Correlations with the boiling temperatures of the solvents and a dependence on
      the length of the side chain of the imidazolium cations show that dispersion
      interactions modify the phase transition, which is mainly determined by Coulomb
      forces. Critical concentrations, widths of the phase diagrams and the slopes of
      the diameter are different for the solutions in protic and aprotic solvents. The
      phase diagrams of the solutions in alcohols and water get a lower critical
      solution point when represented in RPM variables.

PMID- 21715855
TI  - Simulations of imidazolium ionic liquids: when does the cation charge
      distribution matter?
AB  - We compare the properties of models of liquids and crystals constructed from a
      number of intermolecular potentials for dimethylimidazolium chloride [dmim][Cl].
      The force fields differ in the charge distribution in the cation but all include
      short range interactions which determine the shape of the cation. In addition to
      'realistic' models intended for simulation of [dmim][Cl] we take two extreme
      'unrealistic' models in which the cation charge is localized on the ring atoms or
      at the ring centre in order to study the effects of the cation charge
      distribution. The effects of polarizability are investigated by using shell
      models for the chloride ion. We find that, while equilibrium properties such as
      energetics, crystal structure, liquid structure and charge screening depend on
      the charge distribution in the cation but are little affected by including
      polarizability, dynamical properties such as diffusion are strongly affected by
      polarizability.

PMID- 21715856
TI  - Cooperative dipolar relaxation of a glycerol molecular cluster in nanoscale
      confinement-a computer simulation study.
AB  - We performed an all-atoms molecular dynamics simulation of a glycerol molecular
      cluster confined in single-walled carbon nanotubes of different diameters to
      study the confinement size effect on the dipolar relaxation of glycerol
      molecules. We show that the many-body approach proposed by Dissado and Hill can
      be directly applied to simulation data and provides quantitative information
      concerning the cooperative nature of the dipolar relaxation of molecules in
      nanoscale confinement.

PMID- 21715857
TI  - Precipitation diagram of calcium carbonate polymorphs: its construction and
      significance.
AB  - In order to interpret the formation mechanism of calcium carbonate polymorphs, we
      propose and construct a new 'precipitation diagram', which has two variables: the
      driving force for nucleation and temperature. The precipitation experiments were
      carried out by mixing calcium chloride and sodium carbonate aqueous solutions. As
      a result, a calcite-vaterite co-precipitation zone, a vaterite precipitation
      zone, a vaterite-aragonite co-precipitation zone and an aragonite precipitation
      zone can be defined. Theoretical considerations suggest that the steady state
      nucleation theory can explain well the appearance of these four zones, and the
      first-order importance of the temperature dependency of surface free energy in
      the nucleation of aragonite. Furthermore, the addition of an impurity will likely
      result in the change of these energies, and this precipitation diagram gives a
      new basis for interpreting the nature of the polymorphs precipitated in both
      inorganic and biological environments.

PMID- 21715858
TI  - Geometric frustration in small colloidal clusters.
AB  - We study the structure of clusters in a model colloidal system with competing
      interactions using Brownian dynamics simulations. A short-ranged attraction
      drives clustering, while a weak, long-ranged repulsion is used to model
      electrostatic charging in experimental systems. The former is treated with a
      short-ranged Morse attractive interaction, the latter with a repulsive Yukawa
      interaction. We consider the yield of clusters of specific structure as a
      function of the strength of the interactions, for clusters with m = 3,4,5,6,7,10
      and 13 colloids. At sufficient strengths of the attractive interaction (around
      10k(B)T), the average bond lifetime approaches the simulation timescale and the
      system becomes nonergodic. For small clusters, m<=5, where geometric frustration
      is not relevant, despite nonergodicity, for sufficient strengths of the
      attractive interaction the yield of clusters which maximize the number of bonds
      approaches 100%. However for m = 7 and higher, in the nonergodic regime we find a
      lower yield of these structures where we argue geometric frustration plays a
      significant role. m = 6 is a special case, where two structures, of octahedral
      and C(2v) symmetry, compete, with the latter being favoured by entropic
      contributions in the ergodic regime and by kinetic trapping in the nonergodic
      regime. We believe that our results should be valid as long as the one-component
      description of the interaction potential is valid. A system with competing
      electrostatic repulsions and van der Waals attractions may be such an example.
      However, in some cases, the one-component description of the interaction
      potential may not be appropriate.

PMID- 21715859
TI  - Understanding the problem of glass transition on the basis of elastic waves in a
      liquid.
AB  - We propose that the properties of a glass transition can be understood on the
      basis of elastic waves. Elastic waves originating from atomic jumps in a liquid
      propagate local expansion due to the anharmonicity of the interatomic potential.
      This creates dynamic compressive stress, which increases the activation barrier
      for other events in a liquid. The non-trivial point is that the range of
      propagation of high-frequency elastic waves, d(el), increases with liquid
      relaxation time tau. A self-consistent calculation shows that this increase gives
      the Vogel-Fulcher-Tammann (VFT) law. In the proposed theory, we discuss the
      origin of two dynamic crossovers in a liquid: (1) the crossover from exponential
      to non-exponential and from Arrhenius to VFT relaxation at high temperature and
      (2) the crossover from the VFT to a more Arrhenius-like relaxation at low
      temperature. The corresponding values of tau at the two crossovers are in
      quantitative parameter-free agreement with experiments. The origin of the second
      crossover allows us to reconcile the ongoing controversy surrounding the possible
      divergence of tau. The crossover to Arrhenius relaxation universally takes place
      when d(el) reaches system size, thus avoiding divergence and associated
      theoretical complications such as identifying the nature of the phase transition
      and the second phase itself. Finally, we discuss the effect of volume on tau and
      the origin of liquid fragility.

PMID- 21715860
TI  - Density-functional theory of the magnetic anisotropy of nanostructures: an
      assessment of different approximations.
AB  - We discuss the multiple technical choices that have to be made in ab initio
      density-functional calculations of the magnetic anisotropy of supported
      nanostructures: (i) choice of the exchange-correlation functional, (ii) degree of
      optimization of the geometry of the adsorbate/substrate complex, (iii) magnetic
      anisotropy energy calculated self-consistently or via the 'force theorem', (iv)
      calculations based on slab models of the substrate or using a Green's function
      describing a semi-infinite substrate, (v) full potential approach or atomic
      sphere approximation. Using isolated Fe and Co atoms on Pt(111) as an example we
      demonstrate that by using a judicious combination of relatively crude
      approximations (complete neglect of structural relaxation, local exchange
      correlation functional,...) seemingly good agreement with experimental anisotropy
      energies can be achieved, while the calculated orbital moments remain small. At a
      higher level of theory (relaxed adsorbate/substrate complex, gradient-corrected
      functionals,...) providing a realistic geometry of the adsorbate/substrate
      complex and hence a correct description of the interaction between the magnetic
      adatom and its ligands, anisotropy energies are also in semi-quantitative
      agreement with experiment, while the orbital moments of the adatoms are much too
      small. We suggest that the anisotropy energies provided by both approaches should
      be considered as lower limits of the real anisotropies. Without relaxation the
      ligand effect coupling the orbital moments of the adatom to the heavy atoms of
      the substrate is underestimated, while in a relaxed adsorbate/substrate complex
      the lack of orbital dependence of the exchange potential combined with a strong
      hybridization of adatom and substrate states leads to a strong underestimation of
      the orbital moment. We have briefly explored the influence of post-density
      functional corrections. Adding a modest on-site Coulomb repulsion to the d states
      of the adatom (in a DFT+U approach) leads to a modest increase of spin and
      orbital moments of the adatom accompanied by a slow decrease of the induced
      moments, leaving the anisotropy energy almost unchanged.

PMID- 21715861
TI  - Finite-size scaling in band ferromagnets with non-universal critical behavior.
AB  - The ultra-high sensitivity of the ferromagnetic resonance (FMR) technique has
      been fully exploited to study the finite-size effects in the critical region near
      the ferromagnetic to paramagnetic phase transition in Cr(75-x)Fe(25+x) (x = 0, 5)
      thin films of high structural and magnetic quality. Conclusive experimental
      evidence is provided for the validity of finite-size scaling. Irrespective of the
      film thickness and composition, the critical exponents beta, gamma and nu for
      spontaneous magnetization, initial magnetic susceptibility and spin-spin
      correlation length retain their bulk values so that no dimensionality crossover
      occurs within the film thickness range covered in the FMR experiments. The
      present results indicate that (i) like Cr(75-x)Fe(25+x), the previously studied
      Fe, Co, Ni, and CoNi(3) thin films behave as itinerant-electron (band)
      ferromagnets in which the isotropic long-range interactions between spins decay
      as J(r)~r(-(d+sigma)) (sigma>0), and (ii) the lattice dimensionality d, spin
      dimensionality m, and range of spin-spin interactions (via the material-specific
      parameter sigma) decide the (non-universal) values of the critical exponents.

PMID- 21715862
TI  - Electrical and magnetic properties of La(0.35)Sr(0.65)Ti(1-x)Fe(x)O(3) thin
      films.
AB  - We report that the La(0.35)Sr(0.65)Ti(1-x)Fe(x)O(3) system forms a solid solution
      within the composition range 0<=x<=0.5 and a room temperature magnetic
      semiconductor phase exists at x = 0.20. This system shows an anomalous Hall
      effect and is ferromagnetic with a large moment per Fe ion. The results show that
      the strong La doping provides sufficient carriers to the system to maintain
      carrier-mediated ferromagnetism for low Fe doping. Furthermore, the presence of
      ferromagnetism within this phase space raises the possibility that the
      conduction, and hence the magnetism, could be electronically controlled.

PMID- 21715863
TI  - Fracture in glassy polymers: a molecular modeling perspective.
AB  - Over the past 25 years, molecular modeling and simulations have provided
      important insights into the physics of deformation and fracture of glassy
      polymers. This review presents an overview of key results discussed in the
      context of experimentally observed polymer behavior. Both atomistic and coarse
      grained polymer models have been used in different deformation protocols to study
      elastic properties, shear yielding, creep, physical aging, strain hardening and
      crazing. Simulations reproduce most of the macroscopic features of plasticity in
      polymer glasses such as stress-strain relations and creep response, and reveal
      information about the underlying atomistic processes. Trends of the shear yield
      stress with loading conditions, temperature and strain rate, and the atomistic
      dynamics under load have been systematically explored. Most polymers undergo
      physical aging, which leads to a history-dependent mechanical response.
      Simulations of strain hardening and crazing demonstrate the nature of polymer
      entanglements in the glassy state and the role of local plasticity and provide
      insight into the origin of fracture toughness of amorphous polymers.

PMID- 21715864
TI  - Forward flux sampling for rare event simulations.
AB  - Rare events are ubiquitous in many different fields, yet they are notoriously
      difficult to simulate because few, if any, events are observed in a conventional
      simulation run. Over the past several decades, specialized simulation methods
      have been developed to overcome this problem. We review one recently developed
      class of such methods, known as forward flux sampling. Forward flux sampling uses
      a series of interfaces between the initial and final states to calculate rate
      constants and generate transition paths for rare events in equilibrium or
      nonequilibrium systems with stochastic dynamics. This review draws together a
      number of recent advances, summarizes several applications of the method and
      highlights challenges that remain to be overcome.

PMID- 21715865
TI  - Classical density functional theory: an ideal tool to study heterogeneous crystal
      nucleation.
AB  - Density functional theory provides an ideal microscopic theory to address
      freezing and crystallization problems. We review the application of static
      density functional theory for the calculation of equilibrium phase diagrams. We
      also describe the dynamical extension of density functional theory for systems
      governed by overdamped Brownian dynamics. Applications of density functional
      theory to crystallization problems, in particular to heterogeneous crystal
      nucleation and subsequent crystal growth, are summarized. Heterogeneous
      nucleation at an externally imposed nucleation cluster is discussed in detail, in
      particular for a simple two-dimensional dipolar system. Finally the relation of
      dynamical density functional theory and the phase field crystal approach are
      outlined.

PMID- 21715866
TI  - Computer simulation studies of finite-size broadening of solid-liquid interfaces:
      from hard spheres to nickel.
AB  - Using molecular dynamics (MD) and Monte Carlo (MC) simulations interfacial
      properties of crystal-fluid interfaces are investigated for the hard sphere
      system and the one-component metallic system Ni (the latter modeled by a
      potential of the embedded atom type). Different local order parameters are
      considered to obtain order parameter profiles for systems where the crystal phase
      is in coexistence with the fluid phase, separated by interfaces with (100)
      orientation of the crystal. From these profiles, the mean-squared interfacial
      width w(2) is extracted as a function of system size. We rationalize the
      prediction of capillary wave theory that w(2) diverges logarithmically with the
      lateral size of the system. We show that one can estimate the interfacial
      stiffness [Formula: see text] from the interfacial broadening, obtaining
      [Formula: see text] for hard spheres and [Formula: see text] for Ni.

PMID- 21715867
TI  - Phase-field modelling for metals and colloids and nucleation therein-an overview.
AB  - Phase-field modelling, as it is understood today, is still a young discipline in
      condensed matter physics, which established itself for that class of systems in
      condensed matter physics, which can be characterized by domains of different
      phases separated by a distinct interface. Driven out of equilibrium, their
      dynamics results in the evolution of those interfaces, during which those might
      develop into well-defined structures with characteristic length scales at the
      nano-, micro- or mesoscale. Since the material properties of such systems are, to
      a large extent, determined by those small-scale structures, acquiring a precise
      understanding of the mechanisms that drive the interfacial dynamics is a great
      challenge for scientists in this field. Phase-field modelling is an approach that
      allows us to tackle this challenge simulation-based. This overview summarizes
      briefly the essentials of the conceptual background of the phase-field method, as
      well as recent issues the phase-field community is focusing on, as far as they
      are related to nucleation. To that end a brief introduction to the basic
      understanding underlying the diffuse interface description, which is the
      conceptual backbone of phase-field modelling, is given at the beginning, followed
      by a detailed picture of its achievements so far in applications to nucleation
      phenomena in metals and colloids. Within the most relevant fields of condensed
      matter physics, approached by phase-field modelling until now, applications to
      metallic systems are a traditional domain of phase-field modelling and nucleation
      phenomena therein have been addressed by several groups. This paper provides an
      overview of these. Advances in the field of colloidal systems, on the other hand,
      are only more recent and are addressed here in the context of contributions to
      soft matter physics in general.

PMID- 21715868
TI  - Interplay between alpha(Ti) nucleation and growth during peritectic
      solidification investigated by phase-field simulations.
AB  - The properties of modern TiAl-based alloys with aluminum contents around 45 at.%
      critically depend on the as solidified alpha(Ti) grain structure. Commonly, a
      rather coarse grain structure is obtained if alpha(Ti) forms via the peritectic
      reaction '[Formula: see text]'. Phase-field simulations have been applied to
      perform a case study of grain structure formation during the early peritectic
      growth under unidirectional growth conditions. In the absence of foreign
      nucleation sites, the peritectic alpha(Ti) phase nucleates on the dendritic
      surface of the properitectic beta(Ti) phase. For typical values of the critical
      nucleation undercooling, coarse structures with large elongated grains are
      reproduced. A delicate interplay between nucleation and growth is predicted for
      reduced values of the critical undercooling. In this case, the alloy composition
      is found to play an additional role. An effective grain refinement by frequent
      nucleation is obtained, if potent nucleants can reduce the critical undercooling
      below the local growth undercooling. Complementary Scheil calculations and
      Bridgman experiments show that in situ precipitation of TiB(2) particles can be
      controlled by adequate boron addition. Both, numerical predictions and
      experiments confirm that these particles can act as effective nucleation agents
      and significantly reduce the grain size of alpha(Ti).

PMID- 21715869
TI  - Morphology-dependent crossover effects in heterogeneous nucleation of peritectic
      materials studied via the phase-field method for Al-Ni.
AB  - The application of phase-field modeling to nucleation as a phenomenon at the
      nanoscale is justified, if one takes into account the great success of continuum
      approaches in nanofluidics as proven by the many comparisons to experiments.
      Employed in this manner it provides an approach allowing us to account for
      effects of the physical diffuseness of a nucleus' interface and thereby go beyond
      classical nucleation theory (Granasy and James 2000 J. Chem. Phys. 113 9810;
      Emmerich and Siquieri 2006 J. Phys.: Condens. Matter 18 11121). Here we extend
      the focus of previous work in this field and address the question of how far the
      phase-field method can also be applied to gain further insight into nucleation
      statistics, in particular the nucleation prefactor appearing in the nucleation
      rate. In this context we describe in detail a morphology-dependent crossover
      effect noticeable for the nucleation rate at small driving forces.

PMID- 21715870
TI  - Pattern formation during diffusional transformations in the presence of triple
      junctions and elastic effects.
AB  - We compare different scenarios for dendritic melting of alloys with respect to
      the front propagation velocity. In contrast to conventional dendritic growth,
      selection can here be also due to the presence of a grain boundary or coherence
      strains, and the propagation speed is higher. The most favorable situation is
      partial melting, where two parabolic fronts, one melting and one solidifying
      interface, are moving together, since the process is then determined by diffusion
      in the thin liquid layer. There, and also in phase field simulations of melting
      in peritectic and eutectic systems, we observe a rotation of the triple junction
      relative to the growth direction. Finally, we discuss the role of elastic effects
      due to density and structural differences on solid-state phase transformations,
      and we find that they significantly alter the selection principles. In
      particular, we obtain free dendritic growth even with isotropic surface tension.
      This is investigated by Green's function methods and a phase field approach for
      growth in a channel and illustrated for the formation of a twin phase.

PMID- 21715871
TI  - Phase-field simulations of nuclei and early stage solidification microstructures.
AB  - To investigate the local properties of heterogeneous nuclei on substrates, a
      phase-field model is extended to incorporate volume constraints and a third order
      line tension in the gradient free energy density formulation. The new model is
      applied to sessile drop simulations of Cu nuclei on Ni substrates to precisely
      analyse 3D equilibrium shapes and diffusion processes across the phase
      boundaries. In particular, the formalism with higher order potentials is used to
      investigate the length-scale dependent effect of the line tension on Young's
      force balance at triple lines in 3D. The employment of parallel and adaptive
      simulation techniques is essential for three-dimensional numerical computations.
      Early stage solidification microstructures of cubic Ni crystals are simulated by
      scale-bridging molecular dynamics (MD) and phase-field (PF) simulations. The
      domain of the PF computations is initialized by transferring MD data of the
      atomic positions and of the shape of the nuclei. The combined approach can be
      used to study the responses of microstructures upon nucleation.

PMID- 21715872
TI  - Effect of noise-induced nucleation on grain size distribution studied via the
      phase-field crystal method.
AB  - We contribute to the more detailed understanding of the phase-field crystal model
      recently developed by Elder et al (2002 Phys. Rev. Lett. 88 245701), by focusing
      on its noise term and examining its impact on the nucleation rate in a
      homogeneously solidifying system as well as on successively developing grain size
      distributions. In this context we show that principally the grain size decreases
      with increasing noise amplitude, resulting in both a smaller average grain size
      and a decreased maximum grain size. Despite this general tendency, which we
      interpret based on Panfilis and Filiponi (2000 J. Appl. Phys. 88 562), we can
      identify two different regimes in which nucleation and successive initial growth
      are governed by quite different mechanisms.

PMID- 21715873
TI  - Solid-liquid interfacial energies and equilibrium shapes of nanocrystals.
AB  - We extract the anisotropy of the solid-liquid interfacial energy of small
      crystals using phase field crystal simulations. The results indicate a strong
      dependence of the interfacial energy on the parameters in the phase field crystal
      model determining the position in the solid-liquid coexistence region in the
      phase diagram. Furthermore a size dependence of the anisotropy is shown if the
      crystal shape is reduced to the size of a nucleus.

PMID- 21715874
TI  - An anisotropic phase-field crystal model for heterogeneous nucleation of
      ellipsoidal colloids.
AB  - We derive a generalized model for isotropic as well as anisotropic crystal
      lattice systems of arbitrary Poisson ratio within the framework of the continuum
      phase-field crystal (PFC) approach (Elder and Grant 2004 Phys. Rev. E 70 051606).
      To this end we extend the simplest PFC model defined by a free energy functional,
      which is based upon the Swift-Hohenberg model of pattern formation (Swift and
      Hohenberg 1993 Phys. Rev. A 15 851) to a conservative, anisotropic Langevin
      equation. By studying heterogeneous nucleation of ellipsoidal colloids at a wall,
      we demonstrate the capacity of our approach to contribute to the more precise
      understanding of condensed matter systems built up from non-spherical units at
      the atomic scale. In particular we address the question of how (a) the
      orientation of the ellipsoids as well as (b) the interaction potential with the
      wall determine the resulting contact angle.

PMID- 21715875
TI  - Heterogeneous nucleation and growth of the beta(Ti) phase in the Ti-Al system
      experiments and model calculations.
AB  - The barrier to heterogeneous nucleation of the beta(Ti) phase on TiB(2) and other
      borides has been evaluated using the plane to plane matching model. The results
      are compared to the known nucleation of the alpha(Ti) phase on the beta(Ti)
      phase. According to this comparison, the barrier to heterogeneous nucleation of
      the beta(Ti) phase on TiB(2) can be judged to be small. This is in agreement with
      inoculation experiments. The addition of a Ti-Al-TiB(2) master composite to a
      beta(Ti) solidifying TiAl based alloy leads to a significantly refined
      microstructure. Microsegregations enable us to attribute this refinement to
      refined equiaxed beta(Ti) dendrites. However, model calculations based on the
      hemispherical cap model predict that the refinement via heterogeneous beta(Ti)
      nucleation should be more potent. First calculations indicate that structural
      imperfections of TiB(2) particles limit the nucleation site diameter. Thereby,
      the nucleation barrier is increased and the refinement is less pronounced.

PMID- 21715876
TI  - Phase-field simulation of peritectic solidification closely coupled with
      directional solidification experiments in an Al-36 wt% Ni alloy.
AB  - In this work we present experimental and theoretical investigations of the
      directional solidification of Al-36 wt% Ni alloy. A phase-field approach (Folch
      and Plapp 2005 Phys. Rev. E 72 011602) is coupled with the CALPHAD (calculation
      of phase diagrams) method to be able to simulate directional solidification of Al
      Ni alloy including the peritectic phase Al(3)Ni. The model approach is calibrated
      by systematic comparison to microstructures grown under controlled conditions in
      directional solidification experiments. To illustrate the efficiency of the model
      it is employed to investigate the effect of temperature gradient on the
      microstructure evolution of Al-36 wt% Ni during solidification.

PMID- 21715877
TI  - Kinetics of heterogeneous nucleation on intrinsic nucleants in pure fcc
      transition metals.
AB  - Nucleation during solidification is heterogeneous in nature in an overwhelmingly
      large fraction of all solidification events. Yet, most often the identity of the
      heterogeneous nucleants that initiate nucleation remains a matter of speculation.
      In fact, a series of dedicated experiments needs to be designed in order to
      verify if nucleation of the material under study is based on one type of
      heterogeneous nucleant and if the potency of that nucleant is constant, e.g. for
      a population of individual droplets, or stays constant over time, e.g. throughout
      repeated melting/solidification cycles. In this work it is demonstrated that one
      way to circumvent ambiguities and analyze nucleation kinetics under well-defined
      conditions experimentally is given by performing statistically significant
      numbers of repeated single-droplet experiments. The application of proper
      statistics analyses based upon a non-homogeneous Poisson process is shown to
      yield nucleation rates that are independent of a specific nucleation model. Based
      upon this approach nucleation undercooling measurements on pure Au, Cu and Ni as
      model materials have confirmed that the experimental strategy and analysis method
      are valid. The results are comparable to those obtained by classical nucleation
      theory applied to experimental data that has been verified to comply with the
      assertions that are necessary for applying this model framework. However, the
      results reveal also other complex nucleant-sample interactions such as an initial
      transient undercooling behavior and impurity removal during repeated cycling
      treatments. The transient undercooling behavior has been analyzed by a nucleant
      refining model to provide new insight on the operation of melt fluxing
      treatments.

PMID- 21715878
TI  - Crystal nuclei and structural correlations in two-dimensional colloidal mixtures:
      experiment versus simulation.
AB  - We examine binary mixtures of superparamagnetic colloidal particles confined to a
      two-dimensional water-air interface both by real-space experiments and Monte
      Carlo computer simulations at high coupling strength. In the simulations, the
      interaction is modelled as a pairwise dipole-dipole repulsion. While the ratio of
      magnetic dipole moments is fixed, the interaction strength governed by the
      external magnetic field and the relative composition is varied. Excellent
      agreement between simulation and experiment is found for the partial pair
      distribution functions including the fine structure of the neighbour shells at
      high coupling. Furthermore local crystal nuclei in the melt are identified by
      bond-orientational order parameters and their contribution to the pair structure
      is discussed.

PMID- 21715879
TI  - Competition between heterogeneous and homogeneous nucleation near a flat wall.
AB  - We studied the competition between heterogeneous and homogeneous nucleation of an
      aqueous suspension of charged colloidal spheres close to the container walls.
      Samples of equilibrium crystalline structure were shear-melted and the metastable
      melt left to solidify after the cessation of shear. The crystallization kinetics
      was monitored using time-resolved scattering techniques: at low particle number
      densities n we applied an improved static light scattering method while at large
      particle concentrations ultra-small-angle x-ray scattering was applied for the
      first time. Our results show some unexpected behavior: the heterogeneous
      nucleation at the container walls is delayed in comparison to the homogeneous
      bulk nucleation and its rate density appears surprisingly slightly smaller,
      demonstrating the complexity of the observed crystallization process.

PMID- 21715880
TI  - Phase behaviour of deionized binary mixtures of charged colloidal spheres.
AB  - We review recent work on the phase behaviour of binary charged sphere mixtures as
      a function of particle concentration and composition. Both size ratios Gamma and
      charge ratios Lambda are varied over a wide range. Unlike the case for hard
      spheres, the long-ranged Coulomb interaction stabilizes the crystal phase at low
      particle concentrations and shifts the occurrence of amorphous solids to particle
      concentrations considerably larger than the freezing concentration. Depending on
      Gamma and Lambda, we observe upper azeotrope, spindle, lower azeotrope and
      eutectic types of phase diagrams, all known well from metal systems. Most solids
      are of body centred cubic structure. Occasionally stoichiometric compounds are
      formed at large particle concentrations. For very low Gamma, entropic effects
      dominate and induce a fluid-fluid phase separation. Since for charged spheres the
      charge ratio Lambda is also decisive for the type of phase diagram, future
      experiments with charge variable silica spheres are suggested.

PMID- 21715881
TI  - Spreading dynamics of power-law fluid droplets.
AB  - This paper aims at providing a summary of the theoretical models available for
      non-Newtonian fluid spreading dynamics. Experimental findings and model
      predictions for a Newtonian fluid spreading test are briefly reviewed. Then how
      the complete wetting and partial wetting power-law fluids spread over a solid
      substrate is examined. The possible extension of Newtonian fluid models to power
      law fluids is also discussed.

PMID- 21715882
TI  - Heterogeneous nucleation at a wall near a wetting transition: a Monte Carlo test
      of the classical theory.
AB  - While for a slightly supersaturated vapor the free energy barrier DeltaF(hom)(*),
      which needs to be overcome in a homogeneous nucleation event, may be extremely
      large, nucleation is typically much easier at the walls of the container in which
      the vapor is located. While no nucleation barrier exists if the walls are wet,
      for incomplete wetting of the walls, described via a nonzero contact angle Theta,
      classical theory predicts that nucleation happens through sphere-cap-shaped
      droplets attracted to the wall, and their formation energy is DeltaF(het)(*) =
      DeltaF(hom)(*)f(Theta), with f(Theta) = (1-cosTheta)(2)(2+cosTheta)/4. This
      prediction is tested through simulations for the simple cubic lattice gas model
      with nearest-neighbor interactions. The attractive wall is described in terms of
      a local 'surface field', leading to a critical wetting transition. The variation
      of the contact angle with the strength of the surface field is determined by
      using thermodynamic integration methods to obtain the wall free energies which
      enter Young's equation. Obtaining the chemical potential as a function of the
      density for a system with periodic boundary conditions (and no walls), the
      droplet free energy of a spherical droplet in the bulk is obtained for a wide
      range of droplet radii. Similarly, DeltaF(het)(*) is obtained for a system with
      two parallel walls. We find that the classical theory is fairly accurate if a
      line tension correction for the contact angle is taken into account.

PMID- 21715883
TI  - Modeling and simulations for molecular scale hydrodynamics of the moving contact
      line in immiscible two-phase flows.
AB  - This paper starts with an introduction to the Onsager principle of minimum energy
      dissipation which governs the optimal paths of deviation and restoration to
      equilibrium. Then there is a review of the variational approach to moving contact
      line hydrodynamics. To demonstrate the validity of our continuum hydrodynamic
      model, numerical results from model calculations and molecular dynamics
      simulations are presented for immiscible Couette and Poiseuille flows past
      homogeneous solid surfaces, with remarkable overall agreement. Our continuum
      model is also used to study the contact line motion on surfaces patterned with
      stripes of different contact angles (i.e. surfaces of varying wettability).
      Continuum calculations predict the stick-slip motion for contact lines moving
      along these patterned surfaces, in quantitative agreement with molecular dynamics
      simulation results. This periodic motion is tunable through pattern period
      (geometry) and contrast in wetting property (chemistry). The consequence of stick
      slip contact line motion on energy dissipation is discussed.

PMID- 21715884
TI  - Dynamics of nanodroplets on topographically structured substrates.
AB  - Mesoscopic hydrodynamic equations are solved to investigate the dynamics of
      nanodroplets positioned near a topographic step of the supporting substrate. Our
      results show that the dynamics depends on the characteristic length scales of the
      system given by the height of the step and the size of the nanodroplets as well
      as on the constituting substances of both the nanodroplets and the substrate. The
      lateral motion of nanodroplets far from the step can be described well in terms
      of a power law of the distance from the step. In general the direction of motion
      depends on the details of the effective laterally varying intermolecular forces.
      But for nanodroplets positioned far from the step it is solely given by the sign
      of the Hamaker constant of the system. Moreover, our study reveals that the steps
      always act as a barrier for transporting liquid droplets from one side of the
      step to the other.

PMID- 21715885
TI  - Surface forces and wetting phenomena.
AB  - Conditions for thermodynamic equilibrium of liquid drops on solid substrates are
      presented. It is shown that if surface force (disjoining/conjoining Derjaguin
      pressure) action in a vicinity of the three-phase contact line is taken into
      account the condition of thermodynamic equilibrium is duly satisfied. Then the
      thermodynamic expressions for equilibrium contact angles of drops on solid
      substrates and menisci in thin capillaries are expressed in terms of the
      corresponding Derjaguin isotherm. It is shown that equilibrium contact angles of
      drops vary significantly depending on the vapour pressure in the ambient
      atmosphere, while there is a single, unique equilibrium contact angle in thin
      capillaries. It is also shown that the static advancing contact angle of a drop
      depends on its volume, in agreement with experimental data. In the case of
      menisci in capillaries, the expression for the receding contact angle is deduced,
      with results that are also in agreement with known experimental data.

PMID- 21715886
TI  - Dynamic wetting and spreading and the role of topography.
AB  - The spreading of a droplet of a liquid on a smooth solid surface is often
      described by the Hoffman-de Gennes law, which relates the edge speed, v(e), to
      the dynamic and equilibrium contact angles theta and theta(e) through [Formula:
      see text]. When the liquid wets the surface completely and the equilibrium
      contact angle vanishes, the edge speed is proportional to the cube of the dynamic
      contact angle. When the droplets are non-volatile this law gives rise to simple
      power laws with time for the contact angle and other parameters in both the
      capillary and gravity dominated regimes. On a textured surface, the equilibrium
      state of a droplet is strongly modified due to the amplification of the surface
      chemistry induced tendencies by the topography. The most common example is the
      conversion of hydrophobicity into superhydrophobicity. However, when the surface
      chemistry favors partial wetting, topography can result in a droplet spreading
      completely. A further, frequently overlooked consequence of topography is that
      the rate at which an out-of-equilibrium droplet spreads should also be modified.
      In this report, we review ideas related to the idea of topography induced wetting
      and consider how this may relate to dynamic wetting and the rate of droplet
      spreading. We consider the effect of the Wenzel and Cassie-Baxter equations on
      the driving forces and discuss how these may modify power laws for spreading. We
      relate the ideas to both the hydrodynamic viscous dissipation model and the
      molecular-kinetic theory of spreading. This suggests roughness and solid surface
      fraction modified Hoffman-de Gennes laws relating the edge speed to the dynamic
      and equilibrium contact angle. We also consider the spreading of small droplets
      and stripes of non-volatile liquids in the capillary regime and large droplets in
      the gravity regime. In the case of small non-volatile droplets spreading
      completely, a roughness modified Tanner's law giving the dependence of dynamic
      contact angle on time is presented. We review existing data for the spreading of
      small droplets of polydimethylsiloxane oil on surfaces decorated with micro
      posts. On these surfaces, the initial droplet spreads with an approximately
      constant volume and the edge speed-dynamic contact angle relationship follows a
      power law [Formula: see text]. As the surface texture becomes stronger the
      exponent goes from p = 3 towards p = 1 in agreement with a Wenzel roughness
      driven spreading and a roughness modified Hoffman-de Gennes power law. Finally,
      we suggest that when a droplet spreads to a final partial wetting state on a
      rough surface, it approaches its Wenzel equilibrium contact angle in an
      exponential manner with a time constant dependent on roughness.

PMID- 21715887
TI  - Wetting dynamics of thin liquid films and drops under Marangoni and centrifugal
      forces.
AB  - This paper presents an experimental study on thin liquid drops and films under
      the combined action of centrifugal forces due to rotation and radial Marangoni
      forces due to a corresponding temperature gradient. We shall examine thinning of
      a given liquid layer both with and without rotation and also consider the onset
      of the fingering instability in a completely wetting liquid drop. In many of the
      experiments described here, we use an interferometric technique which provides
      key information on height profiles. For thick rotating films in the absence of a
      temperature gradient, when an initially thick layer of fluid is spun to angular
      velocities where the classical Newtonian solution is negative, the fluid never
      dewets for the case of a completely wetting fluid, but leaves a microscopic
      uniform wet layer in the center. Similar experiments with a radially inward
      temperature gradient reveal the evolution of a radial height profile given by
      h(r) = A(t)r(alpha), where A(t) decays logarithmically with time, and [Formula:
      see text]. In the case where there is no rotation, small centrally placed drops
      show novel retraction behavior under a sufficiently strong temperature gradient.
      Using the same interferometric arrangement, we observed the onset of the
      fingering instability of small drops placed at the center of the rotating
      substrate in the absence of a temperature gradient. At the onset of the
      instability, the height profile for small drops is more complex than previously
      assumed.

PMID- 21715888
TI  - Influence of solid-liquid interactions on dynamic wetting: a molecular dynamics
      study.
AB  - Large-scale molecular dynamics (MD) simulations of liquid drops spreading on a
      solid substrate have been carried out for a very wide range of solid-liquid
      interactions and equilibrium contact angles. The results for these systems are
      shown to be consistent with the molecular-kinetic theory (MKT) of dynamic
      wetting, which emphasizes the role of contact-line friction as the principal
      channel of energy dissipation. Several predictions have been confirmed. These
      include a quantitative link between the dynamics of wetting and the work of
      adhesion and the existence of an optimum equilibrium contact angle that maximizes
      the speed of wetting. A feature of the new work is that key parameters (kappa(0)
      and lambda), normally accessible only by fitting the MKT to dynamic contact angle
      data, are also obtained directly from the simulations, with good agreement
      between the two sources. This validates the MKT at some fundamental level.
      Further verification is provided by contact angle relaxation studies, which also
      lend support to the interfacial tension relaxation process invoked in
      Shikhmurzaev's hydrodynamic model of dynamic wetting.

PMID- 21715889
TI  - Imbibition through an array of triangular posts.
AB  - We present and interpret simulation results showing how a fluid moves on a
      hydrophilic substrate patterned by a square array of triangular posts. We
      demonstrate that the shape of the posts leads to anisotropic spreading, and
      discuss how this is influenced by the different ways in which the posts can pin
      the advancing front.

PMID- 21715890
TI  - Dynamic wetting with viscous Newtonian and non-Newtonian fluids.
AB  - We examine various aspects of dynamic wetting with viscous Newtonian and non
      Newtonian fluids. Rather than concentrating on the mechanisms that relieve the
      classic contact line stress singularity, we focus on the behavior in the wedge
      flow near the contact line which has the dominant influence on wetting with these
      fluids. Our experiments show that a Newtonian polymer melt composed of highly
      flexible molecules exhibits dynamic wetting behavior described very well by
      hydrodynamic models that capture the critical properties of the Newtonian wedge
      flow near the contact line. We find that shear thinning has a strong impact on
      dynamic wetting, by reducing the drag of the solid on the fluid near the contact
      line, while the elasticity of a Boger fluid has a weaker impact on dynamic
      wetting. Finally, we find that other polymeric fluids, nominally Newtonian in
      rheometric measurements, exhibit deviations from Newtonian dynamic wetting
      behavior.

PMID- 21715891
TI  - Dynamics of wetting: from inertial spreading to viscous imbibition.
AB  - We report the influence of the nature of boundaries on the dynamics of wetting.
      We review some work recently published and highlight new experimental
      observations. Our paper begins with the spreading of drops on substrates and
      demonstrates how the exponents of the spreading laws are affected either by the
      surface chemistry or by the droplet shape. We then discuss the imbibition of
      completely and partially wetting fluids into channels and over microtextured
      surfaces. Starting with the one-dimensional imbibition of completely wetting
      liquids in tubes and surface textures, we show that (i) shape variations of
      channels change the power-law response of the imbibition and (ii) the geometrical
      parameters of a surface roughness change the spreading behavior. For partially
      wetting fluids, we observe directionally dependent spreading: polygonal wetted
      domains can be obtained. We conclude with a tabular summary of our findings,
      allowing us to draw connections between the different systems investigated, and
      shed light on open questions that remain to be addressed.

PMID- 21715892
TI  - Enhanced droplet spreading due to thermal fluctuations.
AB  - The lubrication equation that governs the dynamics of thin liquid films can be
      augmented to account for stochastic stresses associated with the thermal
      fluctuations of the fluid. It has been suggested that under certain conditions
      the spreading rate of a liquid drop on a surface will be increased by these
      stochastic stresses. Here, an atomistic simulation of a spreading drop is
      designed to examine such a regime and provide a quantitative assessment of the
      stochastic lubrication equation for spreading. It is found that the atomistic
      drop does indeed spread faster than the standard lubrication equations would
      suggest and that the stochastic lubrication equation of Grun et al (2006 J. Stat.
      Phys. 122 1261-91) predicts the spread rate.

PMID- 21715893
TI  - Some specificities of wetting by cyanobiphenyl liquid crystals.
AB  - The present paper provides an up to date restatement of the wetting behaviour of
      the series of cyanobiphenyl liquid crystals (LCs) on usual substrates, i.e.
      oxidized silicon wafers, water and glycerol, at both the macroscopic and
      microscopic scale, in the nematic range of temperature. We show that on water the
      systems are close to a wetting transition, especially 5CB and 7CB. In that case,
      the wetting behaviour is controlled by the presence of impurities. On a
      mesoscopic scale, we observe for all our (thin LC film-substrate) systems an
      identical, complex, but well defined general scenario, not accounted for by the
      available models. In the last part, we present a study on line tension which
      results from the specific organization of LCs at the edge of the nematic film. We
      report preliminary results on two-dimensional film coalescence where this line
      tension plays a major role.

PMID- 21715894
TI  - Reactive wetting in metal-metal systems.
AB  - Wetting and spreading in high temperature reactive metal-metal systems is of
      significant importance in many joining processes. An overview of reactive wetting
      is presented outlining the principal differences between inert and reactive
      wetting. New experimental evidence is presented that identifies an early time
      regime in reactive wetting in which spreading occurs without macroscopic
      morphological change of the solid-liquid interface. This regime precedes the
      heavily studied reactive wetting regime. Additional new experimental evidence is
      presented of kinetic roughening in a high temperature reactive system.
      Quantitative characterization of this roughening reveals similarities with room
      temperature systems. These new data provide evidence that supports the existence
      of several sequential time regimes in the reactive wetting process in which
      different physicochemical phenomena are dominant.

PMID- 21715895
TI  - Post-Tanner stages of droplet spreading: the energy balance approach revisited.
AB  - The spreading of a circular liquid drop on a solid substrate can be described in
      terms of the time evolution of its base radius R(t). In complete wetting, the
      quasistationary regime (far away from initial and final transients) typically
      obeys the so-called Tanner law, with R~t(alpha(T)), alpha(T) = 1/10. Late-time
      spreading may differ significantly from the Tanner law: in some cases the drop
      does not thin down to a molecular film and instead reaches an equilibrium pancake
      like shape; in other situations, as revealed by recent experiments with
      spontaneously spreading nematic crystals, the growth of the base radius
      accelerates after the Tanner stage. Here we demonstrate that these two seemingly
      conflicting trends can be reconciled within a suitably revisited energy balance
      approach, by taking into account the line tension contribution to the driving
      force of spreading: a positive line tension is responsible for the formation of
      pancake-like structures, whereas a negative line tension tends to lengthen the
      contact line and induces an accelerated spreading (a transition to a faster power
      law for R(t) than in the Tanner stage).

PMID- 21715896
TI  - Gecko adhesion pad: a smart surface?
AB  - Recently, it has been shown that humidity can increase the adhesion of the
      spatula pads that form the outermost (adhesive) surface of the tokay gecko feet
      by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive
      forces), although the mechanism by which the enhancement is realized is still not
      well understood. A change in the surface hydrophobicity of a gecko setal array is
      observed when the array, which supports the spatulae, is exposed to a water drop
      for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance
      (HLB), and therefore of the conformation of the surface proteins. A surface force
      apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and
      friction forces, while shearing the setal array against a silica surface under
      (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water.
      The adhesion increased in the humid environment but greatly diminished in water.
      Although the adhesion forces changed significantly, the friction forces remained
      unaffected, indicating that the friction between these highly textured surfaces
      is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate
      that the gecko adhesive pads have the ability to exploit environmental conditions
      to maximize their adhesion and stabilize their friction forces. Future designs of
      synthetic dry adhesives inspired by the gecko can potentially include similar
      'smart' surfaces that adapt to their environment.

PMID- 21715897
TI  - Droplet impingement dynamics: effect of surface temperature during boiling and
      non-boiling conditions.
AB  - This study investigates the hydrodynamic characteristics of droplet impingement
      on heated surfaces and compares the effect of surface temperature when using
      water and a nanofluid on a polished and nanostructured surface. Results are
      obtained for an impact Reynolds number and Weber number of approximately 1700 and
      25, respectively. Three discs are used: polished silicon, nanostructured porous
      silicon and gold-coated polished silicon. Seven surface temperatures, including
      single-phase (non-boiling) and two-phase (boiling) conditions, are included.
      Droplet impact velocity, transient spreading diameter and dynamic contact angle
      are measured. Results of water and a water-based single-wall carbon-nanotube
      nanofluid impinging on a polished silicon surface are compared to determine the
      effects of nanoparticles on impinging dynamics. The nanofluid results in larger
      spreading velocities, larger spreading diameters and an increase in early-stage
      dynamic contact angle. Results of water impinging on both polished silicon and
      nanostructured silicon show that the nanostructured surface enhances the heat
      transfer for evaporative cooling at lower surface temperatures, which is
      indicated by a shorter evaporation time. Using a nanofluid or a nanostructured
      surface can reduce the total evaporation time up to 20% and 37%, respectively.
      Experimental data are compared with models that predict dynamic contact angle and
      non-dimensional maximum spreading diameter. Results show that the molecular
      kinetic theory's dynamic contact angle model agrees well with current
      experimental data for later times, but over-predicts at early times. Predictions
      of maximum spreading diameter based on surface energy analyses indicate that
      these models over-predict unless empirical coefficients are adjusted to fit the
      test conditions. This is a consequence of underestimates of the dissipative
      energy for the conditions studied.

PMID- 21715898
TI  - Post-Tanner spreading of nematic droplets.
AB  - The quasistationary spreading of a circular liquid drop on a solid substrate
      typically obeys the so-called Tanner law, with the instantaneous base radius R(t)
      growing with time as R~t(1/10)-an effect of the dominant role of capillary forces
      for a small-sized droplet. However, for droplets of nematic liquid crystals, a
      faster spreading law sets in at long times, so that R~t(alpha) with alpha
      significantly larger than the Tanner exponent 1/10. In the framework of the thin
      film model (or lubrication approximation), we describe this 'acceleration' as a
      transition to a qualitatively different spreading regime driven by a strong
      substrate-liquid interaction specific to nematics (antagonistic anchoring at the
      interfaces). The numerical solution of the thin film equation agrees well with
      the available experimental data for nematics, even though the non-Newtonian
      rheology has yet to be taken into account. Thus we complement the theory of
      spreading with a post-Tanner stage, noting that the spreading process can be
      expected to cross over from the usual capillarity-dominated stage to a regime
      where the whole reservoir becomes a diffusive film in the sense of Derjaguin.

PMID- 21715899
TI  - Shear flow in smectic A liquid crystals.
AB  - This paper considers the onset of a shear-induced instability in a sample of
      smectic A liquid crystal. Unlike many previous models, the usual director n need
      not necessarily coincide with the local smectic layer normal a; the traditional
      Oseen constraint ([Formula: see text]) is not imposed when flow is present. A
      recent dynamic theory for smectic A (Stewart 2007 Contin. Mech. Thermodyn. 18 343
      60) will be used to examine a stationary instability in a simple model when the
      director reorientation and smectic layer distortions are, firstly, assumed not to
      be coupled to the velocity and, secondly, are supposed coupled to the velocity. A
      critical shear rate at which the onset of the instability occurs will be
      identified, together with an accompanying critical director tilt angle and
      critical wavenumber for the associated smectic layer undulations. Despite some
      critical phenomena being largely unaffected by any coupling to the flow, it will
      be shown that the influence of some material parameters, especially the smectic
      layer compression constant B(0) and the coupling constant B(1), upon the critical
      shear rate and critical tilt angle can be greatly affected by flow.

PMID- 21715900
TI  - Diffusion in a tilted periodic potential with entropic barriers.
AB  - Diffusion of Brownian particles in a periodic channel is investigated in the
      presence of a tilted spatially periodic potential. Reduction of spatial
      dimensionality from two or three dimensions to an effective one-dimensional
      system entails the appearance of not only an entropic barrier but also an
      effective diffusion coefficient. It is found that diffusion exhibits striking
      features which are different from those observed in the previous cases. The
      interplay between the potential barriers and entropic barriers makes the
      phenomena richer. Remarkably, two temperature values exist at which the Peclet
      number takes its maximum.

PMID- 21715901
TI  - Boiling-up of superheated liquid argon in an acoustic field.
AB  - The method of lifetime measurement has been used to investigate spontaneous
      cavitation kinetics in superheated liquid argon in weak acoustic fields. It is
      shown that acoustic cavitation may proceed both by the mechanism of homogeneous
      nucleation of the vapor phase and by way of 'build-up' of vapor bubbles generated
      by high-energy particles or the action of some other external factor. Acoustic
      cavitation thresholds are adequately described by homogeneous nucleation theory.

PMID- 21715902
TI  - Phase diagrams of charged colloids from thermodynamic integration.
AB  - We present full phase diagrams (including solid phases) of spherical charged
      colloids, using Monte Carlo sampling and thermodynamic integration of the
      Helmholtz free energy. Colloids and their co- and counterions are described by
      the primitive model for ionic systems that consists of hard-spheres with central
      point charges, while the solvent is taken into account solely through its
      dielectric constant. Two systems are considered: (i) a size-asymmetric system of
      oppositely charged spheres with size ratios q = 0.3 and 0.5 and (ii) a charge-
      and size-asymmetric system with colloid charge Q = 10 and counterions of charge 
      1 in the presence of monovalent added salt. In system (i), for both size ratios,
      the stable solid phase is equivalent to the NaCl crystal where the oppositely
      charged spheres take the lattice positions of Na and Cl ions. In system (ii), the
      phase diagram consists of gas-liquid and fluid-solid coexistence regions. We show
      that added salt stabilizes the fluid phase and shrinks the fluid-solid
      coexistence region, in agreement with experimental and theoretical results.

PMID- 21715903
TI  - Derivation of a non-local interfacial model for 3D wetting in an external field.
AB  - We extend recent studies of 3D short-ranged wetting transitions by deriving an
      interfacial Hamiltonian in the presence of an arbitrary external field. The
      binding potential functional, describing the interaction of the interface and the
      substrate, can still be written in a diagrammatic form, but now includes new
      classes of diagrams due to the coupling to the external potential, which are
      determined exactly. Applications to systems with long-ranged (algebraically
      decaying) and short-ranged (exponentially decaying) external potentials are
      considered at length. We show how the familiar 'sharp-kink' approximation to the
      binding potential emerges, and determine the corrections to this arising from
      interactions between bulk-like fluctuations and the external field. A connection
      is made with earlier local effective interfacial Hamiltonian approaches. It is
      shown that, for the case of an exponentially decaying potential, non-local
      effects have a particularly strong influence on the approach to the critical
      regime at second-order wetting transitions, even when they appear to be sub
      dominant. This is confirmed by Monte Carlo simulation studies of a discretized
      version of a non-local interfacial model.

PMID- 21715904
TI  - Linear relationship statistics in diffusion limited aggregation.
AB  - We show that various surface parameters in two-dimensional diffusion limited
      aggregation (DLA) grow linearly with the number of particles. We find the ratio
      of the average length of the perimeter and the accessible perimeter of a DLA
      cluster together with its external perimeters to the cluster size, and define a
      microscopic schematic procedure for attachment of an incident new particle to the
      cluster. We measure the fractal dimension of the red sites (i.e., the sites such
      that cutting each of them splits the cluster) as equal to that of the DLA
      cluster. It is also shown that the average number of dead sites and the average
      number of red sites have linear relationships with the cluster size.

PMID- 21715905
TI  - Reconstruction of carbon atoms around a point defect of a graphene: a hybrid
      quantum/classical molecular-dynamics simulation.
AB  - We have investigated the rearrangement of carbon atoms around a point defect of a
      graphene using a hybrid ab initio/classical molecular-dynamics (MD) simulation
      method, in which 36 carbon atoms surrounding a point defect are treated by the ab
      initio MD method and the other 475 carbon atoms relatively far from the point
      defect are treated by the classical MD method. We have confirmed a formation of a
      5-1DB defect (a pentagon and a dangling bond) from the time dependence of atomic
      configurations and electron density distributions obtained by our simulation. We
      have found that the pentagon is formed in two different positions around the
      point defect, and that the two positions appear alternately during the
      simulation, the frequency of which increases with increasing temperature.

PMID- 21715906
TI  - Magnetically induced ferroelectricity in TbMnO(3): inverse Goodenough-Kanamori
      interaction.
AB  - Improper ferroelectricity in magnets, as induced by non-centrosymmetric spin-,
      charge- or orbital-ordering, is a branch of the field of multiferroics having
      fascinating physics and a potentially important technological outcome. We focus
      here on ferroelectricity in orthorhombic TbMnO(3), where the magnetic field along
      the a-axis produces a polar collinear spin-arrangement with a rather large in
      plane electric polarization. The mechanism, similar to that occurring in
      orthorhombic HoMnO(3) in the AFM-E phase, is efficiently driven by a large
      modification of the structural properties (such as MnO bond-lengths and Mn-O-Mn
      bond-angles) to favor e(g) electron hopping between Mn with parallel spins. A
      similar mechanism where the t(2g) states are involved is examined through a
      hypothetical collinear spin-structure, resulting in a weaker out-of-plane
      ferroelectric polarization.

PMID- 21715907
TI  - New general scheme for improving accuracy in implementing self-consistent
      iterative calculations: illustration in the STLS theory.
AB  - By imposing the Pauli's exclusion principle and other known exact relations at
      each stage in the self-consistent iteration scheme due to Singwi, Tosi, Land, and
      Sjolander (STLS), we propose an algorithm to obtain accurate results for the
      static structure factor and other related physical quantities in electron
      liquids. Its actual implementation is illustrated in the spin fully polarized
      homogeneous electron liquid. We suggest the usefulness of our idea in improving
      accuracy in other iteration schemes as well.

PMID- 21715908
TI  - Towards first-principles understanding of the metal-insulator transition in fluid
      alkali metals.
AB  - By treating the electron-ion interaction as a perturbation in the first
      principles Hamiltonian, we have calculated the density response functions of a
      fluid alkali metal to find an interesting charge instability due to anomalous
      electronic density fluctuations occurring at some finite wavevector Q in a dilute
      fluid phase above the liquid-gas critical point. Since |Q| is smaller than the
      diameter of the Fermi surface, this instability necessarily impedes the electric
      conduction, implying its close relevance to the metal-insulator transition in
      fluid alkali metals.

PMID- 21715909
TI  - Computational schemes for the ground-state pair density.
AB  - We reconfirm the performance of the initial scheme for calculating the ground
      state pair density (Higuchi and Higuchi 2007 Physica B 387 117, 2008 Phys. Rev. B
      78 125101) by using the alternative approximation of the correlating kinetic
      energy functional. It is shown that about 20% of the correlation energy can be
      reproduced by the initial scheme, irrespective of the approximate form of the
      correlating kinetic energy functional. On the basis of the initial scheme,
      various kinds of schemes that go beyond the initial one can be developed. We
      illustrate two kinds of computational schemes.

PMID- 21715910
TI  - Algorithms for the electronic and vibrational properties of nanocrystals.
AB  - Solving the electronic structure problem for nanoscale systems remains a
      computationally challenging problem. The numerous degrees of freedom, both
      electronic and nuclear, make the problem impossible to solve without some
      effective approximations. Here we illustrate some advances in algorithm
      developments to solve the Kohn-Sham eigenvalue problem, i.e. we solve the
      electronic structure problem within density functional theory using
      pseudopotentials expressed in real space. Our algorithms are based on a nonlinear
      Chebyshev filtered subspace iteration method, which avoids computing explicit
      eigenvectors except at the first self-consistent-field iteration. Our method may
      be viewed as an approach to solve the original nonlinear Kohn-Sham equation by a
      nonlinear subspace iteration technique, without emphasizing the intermediate
      linearized Kohn-Sham eigenvalue problems. Replacing the standard iterative
      diagonalization at each self-consistent-field iteration by a Chebyshev subspace
      filtering step results in a significant speed-up, often an order of magnitude or
      more, over methods based on standard diagonalization. We illustrate this method
      by predicting the electronic and vibrational states for silicon nanocrystals.

PMID- 21715911
TI  - Relativistic optimized effective potential method-application to alkali metals.
AB  - We present a relativistic formulation of the optimized effective potential method
      (ROEP) and its implementation within the Korringa-Kohn-Rostoker multiple
      scattering formalism. The scheme is an all-electron approach, treating core and
      band states formally on the same footing. We use exact exchange (EXX) as an
      approximation to the exchange correlation functional. Numerical four-component
      wavefunctions for the description of core and valence electrons and the
      corresponding ingredients of the ROEP integral equation are employed. The exact
      exchange expression for the valence states is reformulated in terms of the
      electronic Green's function that in turn is evaluated by making use of multiple
      scattering formalism. We present and discuss the application of the formalism to
      non-magnetic alkali metals.

PMID- 21715912
TI  - Multi-orbital effects in optical properties of vanadium sesquioxide.
AB  - Vanadium sesquioxide, V(2)O(3), boasts a rich phase diagram whose description
      necessitates accounting for many-body Coulomb correlations. The spectral
      properties of this compound have been successfully addressed within dynamical
      mean field theory to the extent that results of recent angle-resolved
      photoemission experiments have been correctly predicted. While photoemission
      spectroscopy probes the occupied part of the one-particle spectrum, optical
      experiments measure transitions into empty states and thus provide complementary
      information. In this work, we focus on the optical properties of V(2)O(3) in its
      paramagnetic phases by employing our recently developed 'generalized Peierls
      approach'. We obtain results in overall satisfactory agreement with experiments.
      Further, we rationalize that the experimentally observed temperature dependence
      stems from the different coherence scales of the charge carriers involved.

PMID- 21715913
TI  - Ultrafast lasing due to electron-hole plasma in ZnO nano-multipods.
AB  - Dynamics of stimulated emission and ultrafast lasing in ZnO nano-multipods has
      been investigated with a femtosecond optical Kerr shutter technique. Under band
      to-band excitation with high density, stimulated emission is observed around 395
      400 nm with a mode-like structure. The stimulated emission emerges with an onset
      time of ~2 ps and then the intensity gradually decreases with time having a blue
      shift and a spectral narrowing. The characteristics of the blue-shift and
      spectral narrowing suggest that not only recovery of bandgap renormalization but
      also conversion from an electron-hole plasma (EHP) state to high density
      excitonic state takes place as the carrier density decreases due to recombination
      of electrons with holes. The mode-like structure observed strongly indicates that
      a high quality resonant cavity is formed between the two facets toward the leg
      length direction of individual nano-multipod. These results show that the
      ultrafast lasing observed around 395-400 nm in ZnO nano-multipods comes from
      population inversion in the EHP regime. We also found that the initial carrier
      distribution of the EHP regime in nano-multipods is much wider than that in ZnO
      thin films, implying that the carrier diffusion might be suppressed by their nano
      size structure.

PMID- 21715914
TI  - A quadratic form of the Coulomb operator and an optimization scheme for the
      extended Kohn-Sham models.
AB  - To construct an optimization scheme for an extension of the Kohn-Sham approach, I
      introduce an operator form of the Coulomb interaction. This form is the sum of
      quadratic form pairs, which can be redefined in a self-consistent calculation of
      a multi-reference density functional theory. A detailed derivation of the form is
      given. A fluctuation term introduced in the extended Kohn-Sham scheme is
      expressed in this form for regularization. The present procedure also provides an
      exact derivation of effective negative interactions in charge fluctuation
      channels. Relevance to high-temperature superconductors is discussed.

PMID- 21715915
TI  - Electronic structure and magnetic anisotropy of a constrained Fe chain in an
      electric field.
AB  - The electronic structure and magnetic anisotropy were studied for a constrained
      iron chain in an electric field by means of the first-principles approach. The
      electron induced by the electric field was found to occupy mainly the extended s
      like orbitals which is well hybridized with the d(3z(2)-r(2)) localized orbital.
      The magnetic anisotropy was observed to decrease with the number of induced
      electrons and to depend on the magnetization direction. The magnetization
      perpendicular both to the chain and the electric field modifies the electron
      dispersion relation to be asymmetrical, which implies an expectation of variable
      transport property with both the external electric and magnetic fields.

PMID- 21715916
TI  - Synthesis of TiO(2) nanocrystals controlled by means of the size of magnetic
      elements and the level of doping with them.
AB  - TiO(2) nanocrystals were synthesized by a hydrolysis method combined with a
      thermal treatment. TiO(2) nanocrystals with rutile and anatase structure were
      selectively synthesized by controlling the pH level in the precursor solution,
      and the crystallite size was controlled by changing the reaction temperature.
      Moreover, Co-doped TiO(2) nanocrystals with rutile structure were also
      synthesized by means of the addition of Co to the precursor solution. Secondary
      phases such as Co precipitates and Co oxide were not present in the sample
      tested, with [Co]<10 mol%. With an increase in the Co doping level, the E(g)
      phonon signal at 447 cm(-1) was broadened and shifted to a lower frequency,
      indicating the incorporation of Co into the rutile TiO(2) host lattice and
      lattice expansion. Optical absorption spectra showed that the absorption edge at
      ~3.0 eV corresponded to the band gap of rutile TiO(2) and shifted to the lower
      energy side upon Co doping. These results indicated the possibility of band gap
      engineering of rutile TiO(2) via Co doping. On the other hand, the charge
      transfer gap between O 2p and Co 3d orbitals was also observed for samples with
      Co, suggesting the possibility of photo-induced magnetism in rutile TiO(2)
      nanocrystals, obtained by visible light irradiation.

PMID- 21715917
TI  - Structural and electronic properties of ZnO polycrystals doped with Co.
AB  - Zn(1-x)Co(x)O samples were prepared by a standard solid-state reaction method.
      Zn(1-x)Co(x)O crystals in the wurtzite structure were obtained with a Co
      composition of up to 22.1%. The a- and c-axis lengths increased and decreased,
      respectively, with an increase in Co composition. Raman spectra showed systematic
      broadening of the E(2) (high) phonon mode associated with the increase in Co
      composition, and electronic transitions of Co in the oxygen tetrahedron were
      observed in optical absorption measurement. These results indicated systematic
      substitution of Co into the Zn sites. Furthermore, an additional broad absorption
      band at 2.4-3.3 eV corresponding to the charge transfer (CT) process [Formula:
      see text] was also observed. The Raman spectra showed strong enhancement of the
      LO phonon due to a resonant Raman process induced with the coupling of the LO
      phonon and a photo-excited carriers mediated CT gap. These results suggest the
      possibility of carrier-induced ferromagnetism based on double exchange
      interaction in Zn(1-x)Co(x)O by visible light irradiation.

PMID- 21715918
TI  - Formation of aligned CrN nanoclusters in Cr-delta-doped GaN.
AB  - Cr-delta-doped GaN layers were grown by radio-frequency plasma-assisted molecular
      beam epitaxy on GaN template substrates. Cr flux was supplied without nitrogen
      flow during Cr-delta-doping. Cr incorporation into a narrow thin layer region was
      confirmed with the depth profile measured by secondary ion mass spectrometry.
      Structural properties and Cr atom alignments were studied with transmission
      electron microscopy. It was found that Cr-delta-doped GaN layers were coherently
      grown with Cr or CrGa nanoclusters in the delta-doped region for low temperature
      growth (350, 500  degrees C). It was also found that aligned CrN nanoclusters
      (approximately 5 nm vertical thickness) with NaCl-type structure were formed in
      the delta-doped region for the growth at 700  degrees C.

PMID- 21715919
TI  - Dynamics simulation of a pi-conjugated light-harvesting dendrimer II: phenylene
      based dendrimer (phDG2).
AB  - We investigate the light-harvesting property of a pi-conjugated dendrimer,
      phenylene-based dendrimer (phDG2), by carrying out a semi-classical Ehrenfest
      dynamics simulation based on the time-dependent density functional theory.
      Similar to our previous study of star-shaped stilbenoid phthalocyanine (SSS1Pc),
      phDG2 shows electron and hole transfer from the periphery to the core through a
      pi-conjugated network when an electron is selectively excited in the periphery.
      The one-way electron and hole transfer occurs more easily in dendrimers with
      planar structure than in those with steric hindrance because pi-conjugation is
      well maintained in the planar structure. The present results explain recent
      experiments by Akai et al (2005 J. Lumin. 112 449).

PMID- 21715920
TI  - Spin-phonon coupling in multiferroic YbMnO(3) studied by Raman scattering.
AB  - Hexagonal YbMnO(3) bulk polycrystals were prepared and studied by Raman
      scattering in the temperature range of 15-300 K. A total of 15 phonon modes of
      A(1), E(1) and E(2) type were identified. Some E(2) phonon modes showed anomalous
      temperature variations in frequency at T(N)~80 K, suggesting a coupling between
      the spin and phonon systems below T(N). As another evidence of spin-phonon
      coupling, softening of an A(1)-phonon mode for the O-Mn vibration was observed at
      ~T(N). Substitution of Mn by Al suggests this view.

PMID- 21715921
TI  - Hydrogen peroxide adsorption on Fe-filled single-walled carbon nanotubes: a
      theoretical study.
AB  - We investigated the adsorption of hydrogen peroxide molecules on Fe-filled single
      walled carbon nanotubes (SWNTs) based on density functional theory (DFT)
      calculations. The adsorption possibilities for the hydrogen peroxide molecule
      were tested by finding the minimum energy as a function of distance of the
      molecule from the Fe-filled SWNT. Stable structures were obtained by optimizing
      the hydrogen peroxide (H(2)O(2)) as it was adsorbed on to the Fe-filled SWNT.
      This study may serve as an initial investigation into the possibility of Fe
      filled single-walled carbon nanotubes (SWNTs) as catalyst material for the proton
      exchange membrane fuel cell (PEMFC).

PMID- 21715922
TI  - Transport properties of a biphenyl-based molecular junction system-the electrode
      metal dependence.
AB  - We investigate the transport properties of a biphenyl-dithiol molecule sandwiched
      between electrodes made of metal Y (Y = Cu, Ag and Au) using the non-equilibrium
      Green's function method based on a density functional theory. The electrode metal
      Y has an influence on the coupling between the molecule and electrodes, and thus
      on the transmission peak height. For the transmission T(Y) at the Fermi energy,
      we obtain T(Cu)~T(Ag)<T(Au). As a result, the current value at low bias voltage
      for the junction system with Ag or Cu electrodes is smaller than that for Y = Au.
      At high bias voltage, on the other hand, the current value of an Ag electrode
      system becomes larger than the others due to the higher transmission peak around 
      1.5 eV below the Fermi energy. Besides this, it is shown that the transmission
      peak value for all the electrode metals can be expressed generally as a function
      of a ratio of the coupling between the two phenyl rings to the peak width of the
      projected density of states with respect to a corresponding molecular orbital.

PMID- 21715923
TI  - Raman scattering study of multiferroic Ho(3)Fe(5)O(12) thin films.
AB  - Ho(3)Fe(5)O(12) crystallizes in a body-centered cubic lattice and shows no
      ferroelectricity because of its highly symmetric (centrosymmetric) crystal
      structure. However, in heteroepitaxially grown thin films, Ho(3)Fe(5)O(12) may
      exhibit ferroelectricity because of lattice strains induced by the substrate. In
      this work, heteroepitaxial films of Ho(3)Fe(5)O(12) were grown with different
      thicknesses of 50-160 nm and studied by x-ray diffraction and Raman scattering.
      The results were compared with those of bulk polycrystals to characterize
      residual strains. At room temperature, Raman spectra of films revealed a phonon
      frequency shift from those of bulk samples, showing lattice distortion. There was
      a difference in the lattice distortion scheme between the thinner and thicker
      films. Results of x-ray diffraction were well correlated with the Raman data.
      Raman measurements at 300-800 K showed the existence of lattice strain up to ~650
      K. This suggests a remanent-polarization character of Ho(3)Fe(5)O(12) films up to
      this temperature. Closeness between the magnetic ordering temperature T(N) = 567
      K and T(C)~650 K may bring us the ideal multiferroic material with an enhanced
      magnetoelectric effect at room temperature.

PMID- 21715924
TI  - Time-dependent density-functional theory simulation for electron-ion dynamics in
      molecules under intense laser pulses.
AB  - We have developed a simulation method to describe three-dimensional dynamics of
      electrons and ions in a molecule based on the time-dependent density-functional
      theory. We solve the time-dependent Kohn-Sham equation for electrons employing
      the real-space and real-time method, while the ion dynamics are described in
      classical mechanics by the Ehrenfest method. For an efficient calculation in
      massively parallel computers, the code is parallelized dividing the spatial grid
      points. We apply the method to the Coulomb explosion of the H(2)S molecule under
      an intense and ultrashort laser pulse and investigate the mechanism of the
      process.

PMID- 21715925
TI  - First-principles study on the origin of large thermopower in hole-doped LaRhO(3)
      and CuRhO(2).
AB  - Based on first-principles calculations, we study the origin of the large
      thermopower in Ni-doped LaRhO(3) and Mg-doped CuRhO(2). We calculate the band
      structure and construct the maximally localized Wannier functions from which a
      tight binding Hamiltonian is obtained. The Seebeck coefficient is calculated
      within the Boltzmann's equation approach using this effective Hamiltonian. For
      LaRhO(3), we find that the Seebeck coefficient remains nearly constant within a
      large hole concentration range, which is consistent with the experimental
      observation. For CuRhO(2), the overall temperature dependence of the calculated
      Seebeck coefficient is in excellent agreement with the experiment. The origin of
      the large thermopower is discussed.

PMID- 21715926
TI  - First-principles calculation of the electron dynamics in crystalline SiO(2).
AB  - We present a first-principles description for electron dynamics in crystalline
      SiO(2) induced by an optical field in both weak and intense regimes. We rely upon
      the time-dependent density-functional theory with the adiabatic local-density
      approximation, and a real-space and real-time method is employed to solve the
      time-dependent Kohn-Sham equation. The response calculation to a weak field
      provides us with information on the dielectric function, while the response to an
      intense field shows the optical dielectric breakdown. We discuss the critical
      threshold for the dielectric breakdown of crystalline SiO(2), in comparison with
      the results for diamond.

PMID- 21715927
TI  - Pressure induced phase transitions in PbTiO(3).
AB  - Recent theoretical simulations using density functional theory (DFT) and novel
      low temperature high energy x-ray diffraction experiments clearly show the
      existence of a high pressure morphotropic phase boundary (MPB) in pure PbTiO(3).
      The experiments show a richer phase diagram than the simulations, with multiple
      monoclinic phases (Pm and Cm) in the MPB region. In this paper we examine the MPB
      region in more detail using high precision DFT calculations within the local
      density approximation (LDA) and the Wu-Cohen generalized gradient approximation.
      Our results support the polarization rotation theory and open up fresh
      possibilities for applying chemical pressure to engineer novel electromechanical
      materials. We also explain why the zone-boundary mode is more likely to be stable
      only at higher pressures above ~25 GPa and not at moderate pressures of ~10 GPa,
      using the LDA.

PMID- 21715928
TI  - Quasiparticle band structure of vanadium dioxide.
AB  - Vanadium dioxide is insulating below 340 K in experiments, whereas the band
      structure calculated in the local density approximation (LDA) is gapless. We
      study the self-energy effects using the ab initio GW method. We found that the
      self-energy depends strongly on the energy, and proper treatment of the dynamical
      effect is essential for getting precise quasiparticle energies. Off-diagonal
      matrix elements in the Kohn-Sham basis are also important for disentangling
      bands. Inclusion of the two effects opens up a direct gap. Our results also
      suggest that one-shot GW on top of LDA is not enough, and the impact of self
      consistency is significant.

PMID- 21715929
TI  - A resonating broken symmetry configuration interaction approach for double
      exchange magnetic systems.
AB  - The correct description for ion-radical systems has recently attracted much
      attention from density functional theory (DFT) researchers. Although several
      hybridization schemes using exact (Hartree-Fock) exchange and DFT exchange
      correlation functionals have been proposed, it has been reported that such
      treatments do not work for the description of ion-radical systems. In this study
      we show that combining the exact exchange term in the Kohn-Sham DFT (or the
      Hartree-Fock equation) with the following resonating configuration interaction
      method is effective for the description of double-exchange type molecular
      magnetic interactions. The results are analyzed in relation to the 'many-electron
      self-interaction' concept that was recently proposed by DFT researchers.

PMID- 21715930
TI  - Large-scale ab initio simulations of binary transition metal clusters for storage
      media materials.
AB  - In the quest for ultra-high-density magnetic recording, new materials in the
      nanometre range have attracted much interest over the last decade involving
      intense studies of L1(0) phases of contemporary or future storage media materials
      like FePt or CoPt nanoparticles. Based on large-scale density functional theory
      calculations, we provide a systematic overview of the structural and magnetic
      properties of various morphologies of FePt and CoPt nanoclusters with diameters
      up to 3 nm. In this size range, the ordered multiply twinned morphologies are
      energetically favoured over the nanoclusters with the desired layer type L1(0)
      and high magnetocrystalline anisotropy. Other nanoparticles of interest, like
      FePd, also show a preference for multiply twinned structures or exhibit, as in
      the case of MnPt nanoclusters, a strong tendency for antiferromagnetic ordering
      instead of ferromagnetic order. The compositional trends of the various
      nanoparticles can be traced back to differences in the partial electronic density
      of states of the 3d element.

PMID- 21715931
TI  - Calculation of atomic excitation energies by time-dependent density functional
      theory within a modified linear response.
AB  - Time-dependent density functional theory (TDDFT) has become a standard tool for
      investigation of electronic excited states. However, for certain types of
      electronic excitations, TDDFT is known to give systematically inaccurate results,
      which has been attributed to the insufficiency of conventional exchange
      correlation functionals, such as the local density approximation (LDA). To
      improve TDDFT performance within LDA, a modified linear response (MLR) scheme was
      recently proposed, in which the responses from not only the ground state, but
      also the intermediate excited states are taken into account. This scheme was
      shown to greatly improve TDDFT performance on the prediction of Rydberg and
      charge-transfer excitation energies of molecules. Yet, for a validation of this
      TDDFT-MLR scheme for excitation energies, there remain issues to be resolved
      regarding Rydberg transitions of single atoms before going to larger systems. In
      the present work, we show an adapted algorithm to construct the intermediate
      excited states for rare-gas atoms. With the technique, Rydberg transition
      energies can be well decoded from LDA, as will also be shown in the application
      of the TDDFT-MLR scheme to other types of atoms.

PMID- 21715932
TI  - Theoretical study of the time-dependent phenomenon of photon-assisted tunneling
      through a charged quantum dot.
AB  - We have studied numerically the time-dependent photon-assisted tunneling (TD-PAT)
      process for electrons confined in quantum dots (QDs) by employing the finite
      difference method under the scheme of the TD-density functional theory (DFT). We
      have found the quasi-dark state (quasi-DS), where the injected electron remains
      in the QD. By varying the barrier thickness, we have calculated the TD profile of
      the electron density in a QD, and found the optimal geometry of the lozenge QD.
      We have also discussed how the charged QD modulates the PAT process.

PMID- 21715933
TI  - Total-energy minimization of few-body electron systems in the real-space finite
      difference scheme.
AB  - A practical and high-accuracy computation method to search for ground states of
      few-electron systems is presented on the basis of the real-space finite
      difference scheme. A linear combination of Slater determinants is employed as a
      many-electron wavefunction, and the total-energy functional is described in terms
      of overlap integrals of one-electron orbitals without the constraints of
      orthogonality and normalization. In order to execute a direct energy minimization
      process of the energy functional, the steepest-descent method is used. For
      accurate descriptions of integrals which include bare-Coulomb potentials of ions,
      the time-saving double-grid technique is introduced. As an example of the present
      method, calculations for the ground state of the hydrogen molecule are
      demonstrated. An adiabatic potential curve is illustrated, and the accessibility
      and accuracy of the present method are discussed.

PMID- 21715934
TI  - Generalized Hedin equations and sigmaGsigmaW approximation for quantum many-body
      systems with spin-dependent interactions.
AB  - The Hedin equations for the electron self-energy and the vertex were originally
      derived for a many-electron system with Coulomb interaction (Hedin 1965 Phys.
      Rev. 139 A796). Here, we present a generalized set of Hedin equations for quantum
      many-body systems containing spin-dependent interactions, e.g. spin-orbit and
      spin-spin interactions. The corresponding spin-dependent GW approximation is
      constructed. This work should open the way to describing the interplay of
      correlations and spin-dependent interactions in systems such as quantum dots or
      wires, as well as in interface and surface problems.

PMID- 21715935
TI  - Development of the simulation package 'ELSES' for extra-large-scale electronic
      structure calculation.
AB  - An early-stage version of the simulation package 'ELSES' (extra-large-scale
      electronic structure calculation) is developed for simulating the electronic
      structure and dynamics of large systems, particularly nanometer-scale and ten
      nanometer-scale systems (see www.elses.jp). Input and output files are written in
      the extensible markup language (XML) style for general users. Related pre-/post
      simulation tools are also available. A practical workflow and an example are
      described. A test calculation for the GaAs bulk system is shown, to demonstrate
      that the present code can handle systems with more than one atom species. Several
      future aspects are also discussed.

PMID- 21715936
TI  - QM/MM hybrid calculation of biological macromolecules using a new interface
      program connecting QM and MM engines.
AB  - An interface program connecting a quantum mechanics (QM) calculation engine,
      GAMESS, and a molecular mechanics (MM) calculation engine, AMBER, has been
      developed for QM/MM hybrid calculations. A protein-DNA complex is used as a test
      system to investigate the following two types of QM/MM schemes. In a
      'subtractive' scheme, electrostatic interactions between QM/MM regions are
      truncated in QM calculations; in an 'additive' scheme, long-range electrostatic
      interactions within a cut-off distance from QM regions are introduced into one
      electron integration terms of a QM Hamiltonian. In these calculations, 338 atoms
      are assigned as QM atoms using Hartree-Fock (HF)/density functional theory (DFT)
      hybrid all-electron calculations. By comparing the results of the additive and
      subtractive schemes, it is found that electronic structures are perturbed
      significantly by the introduction of MM partial charges surrounding QM regions,
      suggesting that biological processes occurring in functional sites are modulated
      by the surrounding structures. This also indicates that the effects of long-range
      electrostatic interactions involved in the QM Hamiltonian are crucial for
      accurate descriptions of electronic structures of biological macromolecules.

PMID- 21715937
TI  - Electronic and geometric structures of the blue copper site of azurin
      investigated by QM/MM hybrid calculations.
AB  - The electronic and geometric structures of the copper-binding site in a fully
      solvated azurin were investigated using quantum mechanics (QM) and molecular
      mechanics (MM) hybrid calculations. Two types of computational models were
      applied to evaluate the effects of the environment surrounding the active site.
      In model I, long-distance electrostatic interactions between QM region atoms and
      partial point charges of the surrounding protein moieties and solvent water were
      calculated in a QM Hamiltonian, for which the spin-unrestricted Hartree-Fock
      (UHF)/density functional theory (DFT) hybrid all-electron calculation with the
      B3LYP functional was adopted. In model II, the QM Hamiltonian was not allowed to
      be polarized by those partial point charges. Models I and II provided different
      descriptions of the copper coordination structure, particularly for the
      coordinative bonds including a large dipole. In fact, the Cu-O(Gly45) and Cu
      S(Cys112) bonds are sensitive to the treatment of long-distance electrostatic
      interactions in the QM Hamiltonian. This suggests that biological processes
      occurring in the active site are regulated by the surrounding structures of
      protein and solvent, and therefore the effects of long-range electrostatic
      interactions involved in the QM Hamiltonian are crucial for accurate descriptions
      of electronic structures of the copper active site of metalloenzymes.

PMID- 21715938
TI  - Charge excitations in cuprate and nickelate in resonant inelastic x-ray
      scattering.
AB  - We analyze the resonant inelastic x-ray scattering (RIXS) spectra at the Cu and
      Ni K-edges in La(2)CuO(4) and La(2)NiO(4), respectively. We make use of the
      Keldysh-Green function formalism, in which the RIXS intensity is described by a
      product of the incident-photon-dependent factor and the density-density
      correlation function in the 3d states. The former factor is calculated using the
      4p density of states given by an ab initio band structure calculation and the
      latter using the wavefunctions given by a Hartree-Fock calculation of a
      multiorbital tight-binding model. The initial state is described within the
      Hartree-Fock approximation and the electron correlations on charge excitations
      are treated within the random phase approximation. The calculated RIXS spectra
      reproduce well several characteristic features in the experiments. Although
      several groups have interpreted the RIXS peaks as bound excitons, our calculation
      indicates that they should be interpreted as band-to-band excitations augmented
      by electron correlations. The difference in RIXS spectra between La(2)CuO(4) and
      La(2)NiO(4) is explained from this point of view.

PMID- 21715939
TI  - Adsorption states of the self-assembly of NH(3) molecules on the Si(001) surface.
AB  - Adsorption states of the self-assembly of NH(3) molecules on the Si(001) surface
      are investigated using density-functional theory calculations. H-bond
      interactions between incoming and adsorbed NH(3) molecules produce a strong
      attractive potential field for the incoming molecules. Induced by the H bonds,
      physisorption states are formed on the adsorbed NH(3). Molecular adsorption
      states are formed on a buckled-down Si atom near the adsorbed NH(3). Various
      physisorption, molecular and dissociative adsorption configurations are
      discussed.

PMID- 21715940
TI  - Monte Carlo simulations of diluted magnetic semiconductors using ab initio
      exchange parameters.
AB  - Co doped ZnO (Zn(1-x)Co(x)O) is studied as a prototype material for transition
      metal doped II-VI diluted magnetic semiconductors (DMSs) from first-principles
      and Monte Carlo simulations. The exchange interactions are calculated using the
      Korringa-Kohn-Rostoker (KKR) Green's function method. The exchange coupling
      constants thus obtained are treated in the classical Heisenberg model and the
      magnetic phase transitions are studied by the Monte Carlo technique. Our results
      show that the defect free substitutional DMSs of Zn(1-x)Co(x)O do not sustain
      magnetization at low concentration. At high concentration, we find layered
      magnetic structures. Ferromagnetism, with Curie temperature below room
      temperature, is stable at intermediate Co concentrations. First-principles
      studies with the generalized gradient approximation (GGA) and the GGA together
      with the Hubbard U are discussed with respect to structural and electronic
      properties of ZnO.

PMID- 21715941
TI  - A first-principles study on the Rashba effect in surface systems.
AB  - The Rashba effect in several surface systems, Au(111), Au(110), Ag(111), Sb(111)
      and Si(111)-Bi, is studied by means of first-principles relativistic density
      functional calculations. The importance of the asymmetric behavior around the
      surface atom is emphasized as a crucial factor to determine the magnitude of
      Rashba spin splitting in addition to the size of the spin-orbit coupling. The
      Rashba effect at the Brillouin-zone boundary is generally described with time
      reversal symmetry. Distinctive features in the spin splitting and spin direction
      for a two-dimensional hexagonal system are discussed with the use of symmetry in
      the double group of k.

PMID- 21715942
TI  - First-principles study of magnetic ordering of an Al infinite single-row atomic
      wire.
AB  - In this paper we present a detailed analysis of the atomic and spin-electronic
      structure of an Al infinite single-row atomic wire (Al-ISAW). Our work is based
      on ab initio self-consistent field calculations within the local density
      approximation, and we predict structural transformations during elongation using
      the norm-conserving (NC) and projector augmented-wave (PAW) pseudopotentials. The
      results obtained by the NC pseudopotential are in good agreement with those
      obtained by the PAW pseudopotential. We confirm that the Al-ISAW shows a metal
      insulator transition and fractures when elongated beyond the equilibrium length.
      Then, a wire with antiferromagnetic ordering is found to be the lowest
      energetically. We find that the magnitude of spin polarization in the vicinity of
      nuclei is marginal and does not play an important role in the Peierls
      instability. The present results show that the NC pseudopotential can give an
      accurate physical picture of the atomic and spin-electronic structures of the Al
      ISAW.

PMID- 21715943
TI  - New type of half-metallic antiferromagnet: transition metal pnictides.
AB  - The electronic structures of transition metal pnictides ABX(2), where A and B are
      the transition metal elements and X = N, P, As, Sb, and Bi, with the total
      valence d-electron number of the transition metal ions being ten, are
      investigated in the framework of the first-principles KKR Green's function
      method. Some possible crystal structures such as NiAs-type, NaCl-type,
      chalcopyrite, zinc-blende, wurtzite, and MnP-type structures are assumed.
      Similarly to chalcogenides, a new type of spin-compensated half-metallic
      ferrimagnet is found for the case of nitrides. The stability and magnetic
      transition temperature of these nitrides indicate that they are good candidates
      for spintronics materials. For other cases of pnictides such as P, As, Sb, and
      Bi, the half-metallicity seems not to be realized.

PMID- 21715944
TI  - The effect of water on infrared spectra of DNA.
AB  - The effect of water on infrared (IR) spectra of DNA is studied by using first
      principles calculations based on the hybrid density functional theory. Our
      calculations of frequencies of C = O stretching modes in DNA without water do not
      reproduce the IR spectra, whereas calculations for DNA surrounded by water
      reproduce the IR spectra well. We also find that the energy of adsorption of one
      water molecule around a C = O site is large ([Formula: see text] eV) owing to
      hydrogen bond formation. We therefore conclude that the effect of water plays an
      important role as regards IR spectra of DNA in a water solution.

PMID- 21715945
TI  - Evaluation of stabilization energies in pi-pi and cation-pi interactions involved
      in biological macromolecules by ab initio calculations.
AB  - Non-covalent interactions involving aromatic rings contribute significantly to
      the stability of three-dimensional structures of biological macromolecules.
      Therefore, accurate descriptions of such interactions are crucial in
      understanding the functional mechanisms of biological molecules. However, it is
      also well known that, for some cases where van der Waals interactions make a
      dominant contribution, conventional ab initio electronic structure calculations,
      such as density functional theory, do not produce accurate interaction energies.
      In this study, we evaluated molecular mechanics (MM) calculations for two types
      of interactions involving aromatic rings, pi-pi interactions and cation-pi
      interactions, by comparing our results with those obtained by advanced ab initio
      calculations at the coupled-cluster with singles, doubles and perturbative
      triples level. In structures with stacked aromatic rings, interaction energies
      obtained by MM calculations are overestimated. On the other hand, for cation-pi
      interactions, the energies in MM calculations are significantly underestimated.
      In both cases, addition of an induction energy based on polarization effects also
      fails to improve the estimate given by MM calculations. The results indicate that
      current effective pairwise potentials are inappropriate to represent pi-pi and
      cation-pi interactions.

PMID- 21715946
TI  - Half-metallic interface between a Heusler alloy and Si.
AB  - The interface between the half-Heusler alloy CoFeSi and Si is investigated by
      using first-principles density-functional calculations. Although CoFeSi has not
      been fabricated yet, its formation energy turns out to be negative. Within the
      generalized gradient approximation, CoFeSi shows nearly half-metallic properties,
      and its lattice constant is about 5.38 A; this value is relatively close to the
      lattice constant of Si. We here chiefly investigate the CoFeSi/Si (110)
      interface, and find that the half-metallic properties are almost preserved at a
      specific (110) interface. Furthermore, the interfacial structure which leads to
      the high spin polarization has the lowest energy of the (110) interfacial
      patterns examined in this work. The half-metallicity at the interfaces is
      similarly observed in the densities of states projected onto delocalized sp
      states, and this suggests the relevance of the high spin polarization to
      transport properties.

PMID- 21715947
TI  - The effect of the interface oxidation on tunneling conductance of
      Co(2)MnSi/MgO/Co(2)MnSi magnetic tunnel junction.
AB  - We investigate and discuss the effects of interfacial oxidation on electronic
      structures and tunnel conductance of the Co(2)MnSi/MgO/Co(2)MnSi(001) magnetic
      tunnel junction (MTJ) on the basis of first-principles calculations. It is found
      that the MnSi termination tends to be oxidized compared with the Co termination
      because of the relaxation of atomic positions in the MnSi-terminated interface.
      Furthermore, we found that the single oxide layer inserted on both sides of the
      junction greatly decreases the tunnel conductance of the MTJ in parallel
      magnetization. We concluded that the relaxation of the Mn atomic position in the
      oxidized junction reduces the coupling of the Delta(1) states between the
      Co(2)MnSi electrode and the MgO barrier and causes significant interfacial
      scattering of the majority-spin electrons with Delta(1) symmetry at the oxidized
      layer.

PMID- 21715948
TI  - Carrier-induced noncollinear magnetism in perovskite manganites by first
      principles calculations.
AB  - We have performed noncollinear first-principles density-functional calculations
      of carrier-doped perovskite manganites La(1-x)Sr(x)MnO(3) (0.0<=x<=1.0). In the
      calculated magnetic phase diagram (T = 0) within the collinear magnetic
      configurations, ferromagnetic and several antiferromagnetic configurations
      successively appeared as a ground state with increasing x. The calculated total
      energies of the ferromagnetic and A-type antiferromagnetic phases are almost
      degenerate around the phase boundary, x = 0.5. We found that the noncollinear
      magnetic configurations are stable in a wide range of carrier concentrations
      0.3<=x<=0.6. We discuss the effect of lattice distortions on the stability of the
      noncollinear magnetic phase.

PMID- 21715949
TI  - Theoretical investigation of the electronic structure of the Alq(3)/Mg interface.
AB  - We have studied the atomic geometries and the electronic properties of the tris
      (8-hydroxyquinoline) aluminum (Alq(3))/Mg interface by using density functional
      theoretical calculations. We have found that the chemical bond is formed between
      the O atoms of Alq(3) and the substrate Mg atoms, and the stability of the
      interface structures depends on the number of O-Mg bonds. In the up
      configurations, where two or three O-Mg chemical bonds are formed and the Alq(3)
      molecular dipoles are oriented up to the vacuum side, the work function is
      decreased by as much as 1.1 eV or more. The interface dipole is dominated by the
      orientation of the molecular dipoles of Alq(3). The interface gap state reported
      from experiments is ascribed to the highest occupied molecular orbital (HOMO)
      levels of the down configurations, which may coexist with the dominant up
      configurations.

PMID- 21715950
TI  - Understanding the electronic structure and magnetism of correlated nanosystems.
AB  - In this paper we review recent developments towards a realistic description of
      the electronic structure and magnetism of correlated nanosystems. A new class of
      so-called continuous-time solvers for the quantum impurity problem is discussed,
      which provides a numerically exact solution without systematic errors due to
      imaginary time discretization. These solvers are able to handle general
      interactions, like the full Coulomb vertex. We further show how four-point or
      higher-order correlation functions of the impurity problem can be computed. This
      allows the calculation of dynamical susceptibilities which provide information
      about spin excitations. Moreover, we discuss a principally new many-body scheme
      recently proposed for the description of non-local correlations in strongly
      correlated systems. This approach provides a basis for a many-body description of
      extended correlated nanostructures on a substrate.

PMID- 21715951
TI  - A new structure of Cu complex in Si and its photoluminescence.
AB  - A recent discovery of complicated isotope shifts of the PL 1014 meV line in Cu
      containing silicon, which was made by Thewalt's group, indicates that existing
      models of Cu pairs are not appropriate for accounting for the luminescence
      center. A new structural model has been studied. First-principles calculations
      show that the most probable form of the complex is a four-membered complex which
      is composed of a substitutional Cu associated with three neighboring interstitial
      Cu atoms. The symmetry is C(3v). The formation mechanism of this complex is
      discussed. For interpreting the complicated splitting for the Gamma(4) exciton
      peak, involvement of a non-totally symmetric mode is proposed. The pattern of
      splitting obtained by this model is almost in agreement with the experiment.
      Selection rules beyond the usual treatments are necessary to connect a specific
      exciton peak to the corresponding phonon.

PMID- 21715952
TI  - Crystal and magnetic structure of the R15Si9C compounds (R = Ho, Er, Tb).
AB  - The synthesis of the new compounds R(15)Si(9)C with R = Sm, Gd-Er, Y and
      R(15)Ge(9)C with R = Ce, Pr and Nd has been recently reported; these compounds
      crystallize in the hexagonal La(15)Ge(9)Fe structure type, hP50-P6(3)mc, Z = 2
      (ordered superstructure of La(5)Ge(3) (Mn(5)Si(3)-type, hP 16-P6(3)/mcm, Z = 2)).
      Here we report the results of a neutron diffraction investigation that we have
      performed to study the crystal and magnetic structures of the R(15)Si(9)C
      compounds with R = Tb, Ho and Er. All three compounds see the establishment of
      commensurate magnetic order with a predominantly ferromagnetic interaction.
      Details of mixed antiferro-ferromagnetic spin arrangements (kappa = [000]) (for
      Tb(15)Si(9)C and Ho(15)Si(9)C) or of purely ferromagnetic ordering
      (Er(15)Si(9)C), and of their temperature dependence, are given and linked to the
      different coordination of the four dissimilar rare earth sites. In the Tb and Ho
      compounds the thermal evolution of the magnetic moment values strongly differs
      between the different R sites. The position occupied by the principal carbon has
      been determined (Wyckoff site 2b) and the existence of a second position
      available for the interstitial carbon (Wyckoff site 2a) has been revealed for R =
      Ho, Tb. Moreover, in the Tb and Ho compounds the magnetic moment value of the
      rare earth site R4, surrounding the second interstitial carbon site, is strongly
      reduced if compared to the value on the other rare earth sites. The magnetic
      transition temperatures of all three compounds, i.e. T(C) = 130, 43 and 45 K for
      Tb(15)Si(9)C, Ho(15)Si(9)C and Er(15)Si(9)C, are remarkably high compared to
      those of the parent R(5)Si(3) compounds. The magnetic behaviour of the partly
      filled Tb(5)Si(3)C(0.25) is reported.

PMID- 21715953
TI  - Modelling of epitaxial film growth with an Ehrlich-Schwoebel barrier dependent on
      the step height.
AB  - The formation of mounded surfaces in epitaxial growth is attributed to the
      presence of barriers against interlayer diffusion in the terrace edges, known as
      Ehrlich-Schwoebel (ES) barriers. We investigate a model for epitaxial growth
      using an ES barrier explicitly dependent on the step height. Our model has an
      intrinsic topological step barrier even in the absence of an explicit ES barrier.
      We show that mounded morphologies can be obtained even for a small barrier while
      a self-affine growth, consistent with the Villain-Lai-Das Sarma equation, is
      observed in the absence of an explicit step barrier. The mounded surfaces are
      described by a super-roughness dynamical scaling characterized by locally smooth
      (facetted) surfaces and a global roughness exponent alpha > 1. The thin film
      limit is featured by surfaces with self-assembled three-dimensional structures
      having an aspect ratio (height/width) that may increase or decrease with
      temperature depending on the strength of the step barrier.

PMID- 21715954
TI  - Atomistic magnetization dynamics in nanostructures based on first principles
      calculations: application to Co nanoislands on Cu(111).
AB  - The magnetization dynamics of Co nanoislands on Cu(111) is studied on the atomic
      scale by means of the stochastic Landau-Lifshitz-Gilbert equation. The exchange
      and anisotropy constants of the spin Hamiltonian are computed from first
      principles. We focus on hysteresis loops and magnetic switching in dependence on
      temperature, island size, and strength of an external magnetic field. The
      magnetic switching of nanoislands whose magnetization is reversed on the sub
      nanosecond time scale is found consistent with the Stoner-Wohlfarth theory. We
      separate the superparamagnetic from the ferromagnetic regime and provide evidence
      that nanodomains can exist at least on a sub-picosecond time scale.

PMID- 21715956
TI  - Reconciliation in Cambodia: thirty years after the terror of the Khmer Rouge
      regime.
AB  - During the Khmer Rouge regime one quarter of the Cambodian population was killed
      as a result of malnutrition, overwork and mass killings. Although the regime
      ended 30 years ago, its legacy continues to affect Cambodians. Mental health
      problems as well as feelings of anger and revenge resulting from traumatic events
      experienced during the Khmer Rouge regime are still common in Cambodia. These
      conditions continue to impede social coexistence and the peace-building process
      in society. Thirty years after the Khmer Rouge regime this article gives an
      overview on the status of the country's current reconciliation process and
      recommends potential future steps.

PMID- 21715957
TI  - Psychotherapy and psychosocial care of torture survivor refugees in Hungary: "a
      never-ending journey".

PMID- 21715958
TI  - Evaluating the services of torture rehabilitation programmes: history and
      recommendations.

PMID- 21715959
TI  - Torture rehabilitation: reflections on treatment outcome studies.

PMID- 21715960
TI  - Diversity analysis of diazotrophic bacteria associated with the roots of tea
      (Camellia sinensis (L.) O. Kuntze).
AB  - The diversity elucidation by amplified ribosomal DNA restriction analysis and 16S
      rDNA sequencing of 96 associative diazotrophs, isolated from the feeder roots of
      tea on enriched nitrogen-free semisolid media, revealed the predominance of Gram
      positive over Gram-negative bacteria within the Kangra valley in Himachal
      Pradesh, India. The Gram-positive bacteria observed belong to two taxonomic
      groupings; Firmicutes, including the genera Bacillus and Paenibacillus; and
      Actinobacteria, represented by the genus Microbacterium. The Gram-negative
      bacteria included alpha-Proteobacteria genera Brevundimonas, Rhizobium, and
      Mesorhizobium; gamma-Proteobacteria genera Pseudomonas and Stenotrophomonas; and
      beta-Proteobacteria genera Azospira, Burkholderia, Delftia, Herbaspirillum and
      Ralstonia. The low level of similarity of two isolates, with the type strains
      Paenibacillus xinjiangensis and Mesorhizobium albiziae, suggests the possibility
      of raising species novum. The bacterial strains of different phylogenetic groups
      exhibited distinct carbon-source utilization patterns and fatty acid methyl ester
      profiles. The strains differed in their nitrogenase activities with relatively
      high activity seen in the Gramnegative strains exhibiting the highest similarity
      to Azospira oryzae, Delftia lacustris and Herbaspirillum huttiense.

PMID- 21715961
TI  - Characterization of plant-growth-promoting traits of Acinetobacter species
      isolated from rhizosphere of Pennisetum glaucum.
AB  - A total of 31 Acinetobacter isolates were obtained from the rhizosphere of
      Pennisetum glaucum and evaluated for their plant-growth-promoting traits. Two
      isolates, namely Acinetobacter sp. PUCM1007 and A. baumannii PUCM1029, produced
      indole acetic acid (10-13 microgram/ml). A total of 26 and 27 isolates
      solubilized phosphates and zinc oxide, respectively. Among the mineral
      solubilizing strains, A. calcoaceticus PUCM1006 solubilized phosphate most
      efficiently (84 mg/ml), whereas zinc oxide was solubilized by A. calcoaceticus
      PUCM1025 at the highest solubilization efficiency of 918%. All the Acinetobacter
      isolates, except PUCM1010, produced siderophores. The highest siderophore
      production (85.0 siderophore units) was exhibited by A. calcoaceticus PUCM1016.
      Strains PUCM1001 and PUCM1019 (both A. calcoaceticus) and PUCM1022 (Acinetobacter
      sp.) produced both hydroxamate- and catechol-type siderophores, whereas all the
      other strains only produced catechol-type siderophores. In vitro inhibition of
      Fusarium oxysporum under iron-limited conditions was demonstrated by the
      siderophore-producing Acinetobacter strains, where PUCM1018 was the most potent
      inhibitor of the fungal phytopathogen. Acinetobacter sp. PUCM1022 significantly
      enhanced the shoot height, root length, and root dry weights of pearl millet
      seedlings in pot experiments when compared with controls, underscoring the plant
      growth-promoting potential of these isolates.

PMID- 21715962
TI  - The phylogenetic affiliation of an uncultured population of ammonia-oxidizing
      bacteria harboring environmental sequences of amoA cluster-3.
AB  - We investigated the phylogenetic diversity of ammonia-oxidizing bacteria (AOB) in
      Yellow Sea continental shelf sediment by the cloning and sequencing of PCR
      amplified amoA and 16S rRNA genes. Phylogenetic analysis of the amoA-related
      clones revealed that the diversity of AOB was extremely low at the study site.
      The majority (92.7%) of amoA clones obtained belonged to a single cluster,
      environmental amoA cluster-3, the taxonomic position of which was previously
      unknown. Phylogenetic analysis on AOB-specific 16S rRNA gene sequences also
      demonstrated a very low diversity. All of the cloned 16S rRNA gene sequences
      comprised a single phylotype that belonged to the members of uncultured
      Nitrosospira cluster-1, suggesting that AOB belonging to the uncultured
      Nitrosospira cluster- 1 could carry amoA sequences of environmental amoA cluster
      3.

PMID- 21715963
TI  - Proteomic analysis of global changes in protein expression during exposure of
      gamma radiation in Bacillus sp. HKG 112 isolated from saline soil.
AB  - A Gram-positive bacterium was isolated from the saline soils of Jangpura (U.P.),
      India, and showed high-level of radiation-resistant property and survived upto
      12.5 kGy dose of gamma radiation. The 16S rDNA sequence of this strain was
      examined, identified as Bacillus sp. strain HKG 112, and was submitted to the
      NCBI GenBank (Accession No. GQ925432). The mechanism of radiation resistance and
      gene level expression were examined by proteomic analysis of whole-cell extract.
      Two proteins, 38 kDa and 86.5 kDa excised from SDS-PAGE, which showed more
      significant changes after radiation exposure, were identified by MALDI-TOF as
      being flagellin and S-layer protein, respectively. Twenty selected 2-DE protein
      spots from the crude extracts of Bacillus sp. HKG 112, excised from 2- DE, were
      identified by liquid chromatography mass spectrometry (LC-MS) out of which 16
      spots showed significant changes after radiation exposure and might be
      responsible for the radiation resistance property. Our results suggest that the
      different responses of some genes under radiation for the expression of radiation
      dependent proteins could contribute to a physiological advantage and would be a
      significant initial step towards a full-system understanding of the radiation
      stress protection mechanisms of bacteria in different environments.

PMID- 21715964
TI  - Stereoselective biotransformation of timosaponin A-III by Saccharomyces
      cerevisiae.
AB  - Bioconversion of timosaponin A-III (TA-III), one of the major steroidal saponins
      isolated from the rhizomes of Anemarrhenae asphodeloides Bunge (Liliaceae), was
      investigated in Saccharomyces cerevisiae. Five bioconversion products, denoted
      compounds 2-6, were obtained. Biotransformation metabolite 2 was a stereoisomer
      of TAIII with a specific isotype F-ring and beta-ranged CH3-21, which rarely
      occurs in nature. The structure of 2 was elucidated by extensive spectroscopic
      analysis (H-H COSY, HSQC, HMBC), as well as by high-resolution mass spectral
      analysis. The growth inhibitory activity of compounds 1-6 was assayed against
      four human cancer cell lines, HepG2, H-1299, HT-29, and HCT-116. Compounds 1 and
      2 obviously inhibited the growth of the four types of cancer cells with IC50
      values being less than 19 micrometer. A structure-activity relationship is
      discussed, and the spirostane-ring F in compounds 1 and 2 appears to be the
      critical bioactive moiety for the cell growth inhibitory property.

PMID- 21715965
TI  - Enrichment of CO2-fixing bacteria in cylinder-type electrochemical bioreactor
      with built-in anode compartment.
AB  - Bacterial assimilation of CO2 into stable biomolecules using electrochemical
      reducing power may be an effective method to reduce atmospheric CO2 without
      fossil fuel combustion. For the enrichment of the CO2-fixing bacteria using
      electrochemical reducing power as an energy source, a cylinder-type
      electrochemical bioreactor with a built-in anode compartment was developed. A
      graphite felt cathode modified with neutral red (NR-graphite cathode) was used as
      a solid electron mediator to induce bacterial cells to fix CO2 using
      electrochemical reducing power. Bacterial CO2 consumption was calculated based on
      the variation in the ratio of CO2 to N2 in the gas reservoir. CO2 consumed by the
      bacteria grown in the electrochemical bioreactor (2,000 ml) reached a maximum of
      approximately 1,500 ml per week. Time-coursed variations in the bacterial
      community grown with the electrochemical reducing power and CO2 in the mineral
      based medium were analyzed via temperature gradient gel electrophoresis (TGGE) of
      the 16S rDNA variable region. Some of the bacterial community constituents noted
      at the initial time disappeared completely, but some of them observed as DNA
      signs at the initial time were clearly enriched in the electrochemical bioreactor
      during 24 weeks of incubation. Finally, Alcaligenes sp. and Achromobacter sp.,
      which are capable of autotrophically fixing CO2, were enriched to major
      constituents of the bacterial community in the electrochemical bioreactor.

PMID- 21715966
TI  - Thiazinogeldanamycin, a new geldanamycin derivative produced by Streptomyces
      hygroscopicus 17997.
AB  - A new geldanamycin (GDM) derivative was discovered and isolated from the
      fermentation broth of Streptomyces hygroscopicus 17997. Its chemical structure
      was elucidated as thiazinogeldanamycin by LC-MS, sulfur analysis, and NMR. The
      addition of cysteine to the fermentation medium significantly stimulated the
      production level of thiazinogeldanamycin, suggesting cysteine as a precursor of
      thiazinogeldanamycin production. Although showing a decreased cytotoxicity
      against HepG2 cancer cells, thiazinogeldanamycin exhibited an improved water
      solubility and photostability. Thiazinogeldanamycin may represent the first
      natural GDM derivative characterized so far that uses GDM as its precursor. Its
      appearance also clearly indicates that an appropriate end-point of fermentation
      is of critical importance for the maximal production of GDM by Streptomyces
      hygroscopicus 17997.

PMID- 21715967
TI  - Mass production of aphicidal Beauveria bassiana SFB-205 supernatant with the
      parameter of chitinase.
AB  - Beauveria bassiana SFB-205 supernatant can effectively control cotton aphid
      populations, which is closely associated with its chitinase activity. The present
      work extends to optimizing a culture medium to produce more efficacious
      supernatant in flask conditions, followed by scale-up in 7 L, 300 L and 1.2 KL
      fermentors with the parameter of chitinase. In flask conditions, a combination of
      soluble starch and yeast extract produced the greatest amount of chitinase (5.1
      units/ml) and its supernatant had the highest aphicidal activity. An optimal
      quantitative combination of the two substrates, estimated by a response surface
      method, enabled the supernatant to have 15.7 units/ml of chitinase activity and
      3.7 ml/l of median lethal concentration (LC50) of toxicity against cotton aphid
      adults in laboratory conditions. In the scale-up conditions, overall supernatant
      had 25-28 units/ml of chitinase activity. Decrease in pH and limitation of
      dissolved oxygen (DO) during cultures were significantly related to the yield of
      chitinase. These results suggest that the substrate-dependent chitinase
      production can be background information for optimizing a culture medium, and pH
      and DO are critical factors in maximizing the production in scale-up conditions.

PMID- 21715968
TI  - Biosynthesis of glycosylated derivatives of tylosin in Streptomyces venezuelae.
AB  - Streptomyces venezuelae YJ028, bearing a deletion of the entire biosynthetic gene
      cluster encoding the pikromycin polyketide synthases and desosamine biosynthetic
      enzymes, was used as a bioconversion system for combinatorial biosynthesis of
      glycosylated derivatives of tylosin. Two engineered deoxysugar biosynthetic
      pathways for the biosynthesis of TDP-3-O-demethyl-D-chalcose or TDP-Lrhamnose in
      conjunction with the glycosyltransferaseauxiliary protein pair DesVII/DesVIII
      were expressed in a S. venezuelae YJ028 mutant strain. Supplementation of each
      mutant strain capable of producing TDP-3-O-demethyl- D-chalcose or TDP-L-rhamnose
      with tylosin aglycone tylactone resulted in the production of the 3-O-demethyl- D
      chalcose, D-quinovose, or L-rhamnose-glycosylated tylactone.

PMID- 21715969
TI  - A novel transglutaminase substrate from Streptomyces mobaraensis inhibiting
      papain-like cysteine proteases.
AB  - Transglutaminase from Streptomyces mobaraensis is an enzyme of unknown function
      that cross-links proteins to high molecular weight aggregates. Previously, we
      characterized two intrinsic transglutaminase substrates with inactivating
      activities against subtilisin and dispase. This report now describes a novel
      substrate that inhibits papain, bromelain, and trypsin. Papain was the most
      sensitive protease; thus, the protein was designated Streptomyces papain
      inhibitor (SPI). To avoid transglutaminase-mediated glutamine deamidation during
      culture, SPI was produced by Streptomyces mobaraensis at various growth
      temperatures. The best results were achieved by culturing for 30-50 h at 42
      degrees C, which yielded high SPI concentrations and negligibly small amounts of
      mature transglutaminase. Transglutaminasespecific biotinylation displayed largely
      unmodified glutamine and lysine residues. In contrast, purified SPI from the 28
      degrees C culture lost the potential to be cross-linked, but exhibited higher
      inhibitory activity as indicated by a significantly lower Ki (60 nM vs. 140 nM).
      Despite similarities in molecular mass (12 kDa) and high thermostability, SPI
      exhibits clear differences in comparison with all members of the wellknown family
      of Streptomyces subtilisin inhibitors. The neutral protein (pI of 7.3) shares
      sequence homology with a putative protein from Streptomyces lavendulae, whose
      conformation is most likely stabilized by two disulfide bridges. However,
      cysteine residues are not localized in the typical regions of subtilisin
      inhibitors. SPI and the formerly characterized dispase-inactivating substrate are
      unique proteins of distinct Streptomycetes such as Streptomyces mobaraensis.
      Along with the subtilisin inhibitory protein, they could play a crucial role in
      the defense of vulnerable protein layers that are solidified by transglutaminase.

PMID- 21715970
TI  - Production and characterization of a novel protease from Bacillus sp. RRM1 under
      solid state fermentation.
AB  - A commercially important alkaline protease, produced by Bacillus sp. RRM1
      isolated from the red seaweed Kappaphycus alvarezii (Doty) Doty ex Silva, was
      first recognized and characterized in the present study. Identification of the
      isolated bacterium was done using both biochemical characterization as well as
      16S rRNA gene sequencing. The bacterial strain, Bacillus sp. RRM1, produced a
      high level of protease using easily available, inexpensive agricultural residues
      solid-state fermentation (SSF). Among them, wheat bran was found to be the best
      substrate. Influences of process parameters such as moistening agents, moisture
      level, temperature, inoculum concentration, and co-carbon and co-nitrogen sources
      on the fermentation were also evaluated. Under optimized conditions, maximum
      protease production (i.e., 2081 U/g) was obtained from wheat bran, which is about
      2-fold greater than the initial conditions. The protease enzyme was stable over a
      temperature range of 30-60 degrees C and pH 6-12, with maximum activity at 50
      degrees C and pH 9.0. Whereas the metal ions Na+, Ca2+, and K+ enhanced the
      activity of the enzyme, others such as Hg2+, Cu2+, Fe2+, Co2+, and Zn2+ had
      rendered negative effects. The activity of the enzyme was inhibited by EDTA and
      enhanced by Cu2+ ions, thus indicating the nature of the enzyme as a
      metalloprotease. The enzyme showed extreme stability and activity even in the
      presence of detergents, surfactants, and organic solvents. Moreover, the present
      findings opened new vistas in the utilization of wheat bran, a cheap, abundantly
      available, and effective waste as a substrate for SSF.

PMID- 21715971
TI  - Enhancement of excretory production of an exoglucanase from Escherichia coli with
      phage shock protein A (PspA) overexpression.
AB  - Production of recombinant proteins by excretory expression has many advantages
      over intracellular expression in Escherichia coli. Hyperexpression of a secretory
      exoglucanase, Exg, of Cellulomonas fimi was previously shown to saturate the
      SecYEG pathway and result in dramatic cell death of E. coli. In this study, we
      demonstrated that overexpression of the PspA in the JM101(pM1VegGcexL-pspA)
      strain enhanced excretion of Exg to 1.65 U/ml using shake-flask cultivation,
      which was 80% higher than the highest yield previously obtained from the
      optimized JM101(pM1VegGcexL) strain. A much higher excreted Exg activity of 4.5
      U/ml was further achieved with high cell density cultivation using rich media.
      Furthermore, we showed that the PspA overexpression strain enjoyed an elevated
      critical value (CV), which was defined as the largest quotient between the
      intracellular unprocessed precursor and its secreted mature counterpart that was
      still tolerable by the host cells prior to the onset of cell death, improving
      from the previously determined CV of 20/80 to the currently achieved CV of 45/55
      for Exg. The results suggested that the PspA overexpression strain might tolerate
      a higher level of precursor Exg making use of the SecYEG pathway for secretion.
      The reduced lethal effect might be attributable to the overexpressed PspA, which
      was postulated to be able to reduce membrane depolarization and damage. Our
      findings introduce a novel strategy of the combined application of metabolic
      engineering and construct optimization to the attainment of the best possible E.
      coli producers for secretory/excretory production of recombinant proteins, using
      Exg as the model protein.

PMID- 21715972
TI  - Effect of pulsed electric fields upon accumulation of zinc in Saccharomyces
      cerevisiae.
AB  - Cultures of Saccharomyces cerevisiae were treated with pulsed electric fields to
      improve accumulation of zinc in the biomass. Under optimized conditions, that is,
      on 15 min exposure of the 20 h grown culture to PEFs of 1500 V and 10 microns
      pulse width, accumulation of zinc in the yeast biomass reached a maximum of 15.57
      mg/g d.m. Under optimum zinc concentration (100 microgram/ml nutrient medium),
      its accumulation in the cells was higher by 63% in comparison with the control
      (without PEFs). That accumulation significantly correlated against zinc
      concentration in the medium. Neither multiple exposure of the cultures to PEFs
      nor intermittent supplementation of the cultures with zinc increased the zinc
      accumulation. The intermittent supplementation of the cultures with zinc and
      multiple exposures on PEFs could even reduce the accumulation efficiency,
      respectively, by 57% and 47%.

PMID- 21715973
TI  - Improved poly-epsilon-lysine biosynthesis using Streptomyces noursei NRRL 5126 by
      controlling dissolved oxygen during fermentation.
AB  - The growth kinetics of Streptomyces noursei NRRL 5126 was investigated under
      different aeration and agitation combinations in a 5.0 l stirred tank fermenter.
      Poly-epsilon-lysine biosynthesis, cell mass formation, and glycerol utilization
      rates were affected markedly by both aeration and agitation. An agitation speed
      of 300 rpm and aeration rate at 2.0 vvm supported better yields of 1,622.81 mg/l
      with highest specific productivity of 15 mg/l.h. Fermentation kinetics performed
      under different aeration and agitation conditions showed poly- epsilon-lysine
      fermentation to be a growth-associated production. A constant DO at 40% in the
      growth phase and 20% in the production phase increased the poly-epsilon-lysine
      yield as well as cell mass to their maximum values of 1,992.35 mg/l and 20.73
      g/l, respectively. The oxygen transfer rate (OTR), oxygen utilization rate (OUR),
      and specific oxygen uptake rates (qO2) in the fermentation broth increased in the
      growth phase and remained unchanged in the stationary phase.

PMID- 21715974
TI  - Affinity apheresis for treatment of bacteremia caused by Staphylococcus aureus
      and/or methicillin-resistant S. aureus (MRSA).
AB  - Staphylococcus aureus (SA) bacteremia is associated with high mortality, and
      often results in metastatic infections. The methicillin-resistant SA (MRSA) is an
      urgent health care issue, as nosocomial infections with these bacteria represent
      limited treatment alternatives. Samples of whole blood containing challenge
      inoculums of SA and MRSA strains were passed through columns packed with surface
      heparinized polyethylene beads. The bound bacteria were eluted and quantitatively
      determined by culturing and by real-time PCR. Significant amounts of both SA and
      MRSA adhered to the heparinized beads (more than 65% of inoculated bacteria).
      After rinsing with buffer at high ionic strength, viable bacteria or bacterial
      DNA were eluted from the columns, indicating that the binding was specific. The
      conclusions that can be made from these experiments are that, as earlier reported
      in the literature, the high affinity of SA to heparin is retained in whole blood,
      and MRSA in whole blood binds to heparin with similar or higher affinity than SA.
      It should be possible to lower the amount of SA and/or MRSA from the blood of
      infected patients to levels that could be taken care of by the immune system. In
      previous studies, we have shown that passing blood from septic patients over
      beads coated with end-point-attached, biologically active heparin is a useful
      technique for regulating the levels of heparin-binding cytokine. These findings
      in combination with the present findings indicate the possibility of creating an
      apheresis technology for treatment of sepsis caused by SA and/or MRSA.

PMID- 21715975
TI  - Translating niche-derived signals into neurogenesis: the function of Prox1 in the
      adult hippocampus.

PMID- 21715976
TI  - Expanding the p53 toolkit: a new platform for rapid engineering of the p53 locus
      in vivo.

PMID- 21715977
TI  - JAZ mediates G1 cell cycle arrest by interacting with and inhibiting E2F1.
AB  - We discovered and reported JAZ as a unique dsRNA binding zinc finger protein that
      functions as a direct, positive regulator of p53 transcriptional activity to
      mediate G1 cell cycle arrest in a mechanism involving upregulation of the p53
      target gene, p21. We now find that JAZ can also negatively regulate the cell
      cycle in a novel, p53-independent mechanism resulting from the direct interaction
      with E2F1, a key intermediate in regulating cell proliferation and tumor
      suppression. JAZ associates with E2F1's central DNA binding/dimerization region
      and its C-terminal transactivation domain. Functionally, JAZ represses E2F1
      transcriptional activity in association with repression of cyclin A expression
      and inhibition of G1/S transition. This mechanism involves JAZ-mediated
      inhibition of E2F1's specific DNA binding activity. JAZ directly binds E2F1 in
      vitro in a dsRNA-independent manner, and JAZ's dsRNA binding ZF domains, which
      are necessary for localizing JAZ to the nucleus, are required for repression of
      transcriptional activity in vivo. Importantly for specificity, siRNA-mediated
      "knockdown" of endogenous JAZ increases E2F transcriptional activity and releases
      cells from G1 arrest, indicating a necessary role for JAZ in this transition.
      Although JAZ can directly inhibit E2F1 activity independently of p53, if
      functional p53 is expressed, JAZ may exert a more potent inhibition of cell cycle
      following growth factor withdrawal. Therefore, JAZ plays a dual role in cell
      cycle regulation by both repressing E2F1 transcriptional activity and activating
      p53 to facilitate efficient growth arrest in response to cellular stress, which
      may potentially be exploited therapeutically for tumor growth inhibition.

PMID- 21715978
TI  - The power of chemotherapeutic engineering: arresting cell cycle and suppressing
      senescence to protect from mitotic inhibitors.
AB  - Suppose one drug causes lethal mitotic arrest, another treatment causes
      irreversible senescence and a third drug inhibits cellular mass growth: Could
      cells treated with a combination of all three agents magically emerge alive and
      proliferating? The result of this experiment is presented here. By knowing the
      mechanisms of cell cycle arrest, death and senescence, we can design "rainbow
      combinations" that obediently kill or spare desired cells. Knowledge is power.

PMID- 21715979
TI  - Circovirus and impact of temporary withdrawal of rotavirus vaccines in Spain.
AB  - The Spanish Medicines and Health Products Agency (AEMPS) did not authorize the
      release of new batches of rotavirus vaccines onto the Spanish market since March
      29 (Rotarix(r)) and June 10 (Rotateq(r)), 2010, respectively, due to problems of
      good manufacturing practice (GMP). On November 4, 2010, AEMPS again allowed the
      release of batches of the RotaTeq(r) vaccine. Until March 2010, the average
      vaccination coverage against rotavirus in Spain had reached 40%. We have tried to
      estimate the impact of the temporary withdrawal of these vaccines from the
      Spanish market in terms of disease burden and associated costs. During the five
      months in which neither of the rotavirus vaccines was distributed in Spanish
      pharmacies, 84,450 children were not vaccinated against rotavirus and remain at
      risk, leading to a total avoidable cost between 1,901,498 and 2,172,941 euros.
      The impact of the temporary withdrawal of rotavirus vaccines in Spain may have
      been outstanding. The influence of this event in rotavirus vaccination trust may
      have been even more important.

PMID- 21715980
TI  - E. coli O104:H4: social media and the characterization of an emerging pathogen.
AB  - The 2011 German E. coli O104:H4 outbreak resulted in thousands of cases of
      enterohaemorrhagic illness, with approximately 25% of these progressing to
      develop haemolytic uraemic syndrome (HUS). This high rate of progression to HUS
      was the first indicator that the bacterial cause of illness was not a typical
      enterohaemorrhagic E. coli (EHEC) strain. Collaborative bioinformatic analysis
      while the outbreak was still in progress indicated that the O104:H4 strain was in
      fact an enteroaggregative E. coli (EAEC) strain which had acquired genes for the
      production of Shiga - like toxin.

PMID- 21715983
TI  - Characterization of full-length and proteolytic cleavage fragments of desmoglein
      2 in native human colon and colonic epithelial cell lines.
AB  - The desmosomal cadherin desmoglein-2 (Dsg2) is a transmembrane cell adhesion
      protein that is widely expressed in epithelial and non-epithelial tissues, such
      as the intestine, epidermis, testis, and heart. Dsg2 has been shown to regulate
      numerous cellular processes, including proliferation and apoptosis, and we have
      previously reported that intracellular fragments of Dsg2 promote apoptosis in
      colonic epithelial cells. While several studies have shown that both the
      extracellular and intracellular domains of Dsg2 can be targeted by proteases,
      identification of these putative Dsg2 fragments in colonic epithelial cells has
      not been performed. Here, we report that the mouse monoclonal antibody (mAb)
      AH12.2 binds to the first extracellular domain of Dsg2. Using this antibody along
      with previously described mAb against the extracellular (6D8) and intracellular
      (DG3.10) domains of Dsg2, we characterize the expression and identify the
      cleavage fragments of Dsg2 in colonic epithelial cells. This study provides a
      detailed description of the extracellular and intracellular Dsg2 cleavage
      fragments that are generated in the simple epithelium of the colon and will guide
      future studies examining the relationship of these fragments to cellular fate and
      disease states.

PMID- 21715984
TI  - An epidemiological study of technological disasters in China: 1979-2005.
AB  - Although China has been known for its high frequency and human toll resulting
      from natural disasters, limited information is available to understand the human
      impact of its technological disasters (TD). This study provides a time trend
      analysis of the TD-induced injuries and fatalities since 1979 in mainland China.
      Through reviewing available academic literature and the examination of two public
      accessible databases, descriptive analysis of TD epidemiological profile in China
      was conducted by Emergency Events Database of the Centre for Research on the
      Epidemiology of Disasters in Brussels and Energy-related Severe Accidents
      Database of Paul Scherrer Institute in Switzerland which focuses on energy
      related severe accidents. Implications on health protection policy and global
      health were discussed.

PMID- 21715985
TI  - Why did you order that CBC?

PMID- 21715986
TI  - The role of USMLE scores in selecting residents.

PMID- 21715987
TI  - The role of USMLE scores in selecting residents.

PMID- 21715989
TI  - Commentary: criminal background checks for entering medical students: history,
      current issues, and future considerations.
AB  - In this commentary, the authors aim to contextualize the history and rationale
      for what has become the Association of American Medical Colleges-facilitated
      criminal background check process for entering medical students. As the process
      was being considered, many issues with a standardized process were identified.
      There were concerns that demographic or socioeconomic factors might unfairly
      burden certain applicants or discourage them from applying to medical school. On
      the other hand, a unified, national program would minimize cost and enhance
      quality assurance. The authors discuss these issues. Lessons learned in the first
      three years of the program are also addressed, including some unexpected and
      favorable consequences such as the identification of accepted applicants with at
      risk behaviors (e.g., substance abuse), who would have otherwise gone undetected.
      Several challenges remain, including the fact that the criminal background check
      process creates an enhanced role for prehealth advisors and encourages
      undergraduate institutions to establish standards and processes relating to
      professionalism. While this is, no doubt, an evolving program which needs
      continued oversight and ongoing reevaluation, the authors support the continued
      advancement of the criminal background check process for entering medical
      students.

PMID- 21715990
TI  - Teaching and learning moments: burial in completion.

PMID- 21715991
TI  - Commentary: ambiguity and uncertainty: neglected elements of medical education
      curricula?
AB  - Despite significant advances in scientific knowledge and technology, ambiguity
      and uncertainty are still intrinsic aspects of contemporary medicine. To practice
      confidently and competently, a physician must learn rational approaches to
      complex and ambiguous clinical scenarios and must possess a certain degree of
      tolerance of ambiguity. In this commentary, the authors discuss the role that
      ambiguity and uncertainty play in medicine and emphasize why openly addressing
      these topics in the formal medical education curriculum is critical. They discuss
      key points from original research by Wayne and colleagues and their implications
      for medical education. Finally, the authors offer recommendations for increasing
      medical student tolerance of ambiguity and uncertainty, including dedicating time
      to attend candidly to ambiguity and uncertainty as a formal part of every medical
      school curriculum.

PMID- 21715992
TI  - Commentary: medical student distress: a call to action.
AB  - Studies have found a high prevalence of psychological distress among medical
      students both in the United States and abroad. Distress among medical students
      has serious professional ramifications, including damaging effects on empathy,
      ethical conduct, and professionalism, as well as personal consequences such as
      substance abuse, broken relationships, and suicidal ideation. Given the effect of
      physician distress on quality of care, self-care (including personal appraisal of
      well-being, wellness promotion, and recognition of when help is needed) should be
      recognized as a core competency for physicians. In this issue of Academic
      Medicine, investigators at the Northwestern University Feinberg School of
      Medicine explore the benefits of teaching students to employ a cognitive
      behavioral approach to improving self-care. Beyond its demonstrated short-term
      efficacy, the approach they propose also has potential to help students develop
      the skills necessary to assess and promote resilience throughout their careers.
      Medical schools' responsibility to promote student wellness, however, goes beyond
      teaching students self-care skills and includes establishing an appropriate
      organizational culture and learning environment to promote student health.
      Achieving competency in self-care is a shared responsibility of the individual
      physician/resident/medical student and the organizational environment in which he
      or she functions.

PMID- 21715993
TI  - Commentary: time to sign off on signout.
AB  - The physician signout note is a widely used clinical document that supports
      patient safety and care continuity during patient handoff in the hospital.
      Despite its centrality to patient care, the signout note is not considered an
      official document, and it is, therefore, not generally standardized or taught to
      medical trainees, nor is it usually integrated into electronic health records
      (EHRs). This commentary outlines several of the potential advantages to
      establishing the physician signout note as an official part of the medical
      record, such as the facilitation of information flow between signout notes and
      other parts of the patient chart and the possibility of integrating decision
      support tools into this important aspect of the clinical workflow. The authors
      address frequently encountered concerns regarding the establishment of the
      signout note as an official part of the medical record. They conclude by making
      recommendations for integrating signout notes into EHRs and using modern, social
      Web technologies in such an implementation.

PMID- 21715994
TI  - Criminal background checks upon acceptance to medical school: the right policy at
      the right time.

PMID- 21715995
TI  - Criminal background checks upon acceptance to medical school: the wrong policy at
      the wrong time.

PMID- 21715996
TI  - Medicine and the arts.

PMID- 21715998
TI  - Artist's statement: The Rape of the Sabine Women-sketch detail.

PMID- 21715999
TI  - AM last page: generalizability in medical education research.

PMID- 21716000
TI  - Growth hormone temporarily improves sprint capacity in recreational athletes.

PMID- 21716002
TI  - Does the addition of supervised exercise to conventional treatment improve
      outcomes in acute ankle sprain?

PMID- 21716001
TI  - Diagnostic ultrasound for patients with suspected subacromial disorders: a
      review.

PMID- 21716003
TI  - Hamstring strains in elite footballers: predicting recovery and recurrence.

PMID- 21716004
TI  - Reversal of drug-induced rhabdomyolysis on bone scan.
AB  - A 75-year-old man with prostate cancer was referred for metastatic workup. A Tc
      99m methylene diphosphonate bone scan was performed which revealed diffusely
      increased radiopharmaceutical uptake in the muscles of the arms and thighs. The
      patient was taking simvastatin 80 mg per day and gemfibrozil 600 mg twice a day
      for high cholesterol. The patient reported myalgias, and laboratory evaluation
      was consistent with rhabdomyolysis. After discontinuation of the anticholesterol
      medications, the clinical and laboratory evaluations normalized. Bone scan
      performed 1 year later demonstrated complete resolution of muscle uptake.

PMID- 21716005
TI  - ACR-ASTRO practice guideline for the performance of therapy with unsealed
      radiopharmaceutical sources.
AB  - This guideline is intended to guide appropriately trained and licensed physicians
      performing therapy with unsealed radiopharmaceutical sources. Adherence to this
      guideline should help to maximize the efficacious use of these procedures,
      maintain safe conditions, and ensure compliance with applicable regulations. The
      topics dealt with in this guideline include indications for the use of iodine
      131, both for the treatment of hyperthyroidism and thyroid carcinoma. In
      addition, indications for other less common procedures include those for the use
      of phosphorous-32 in its liquid and colloidal forms, strontium-89, samarium-153,
      and the use of Y-90 antibodies.

PMID- 21716006
TI  - FDG PET/CT in evaluation of pyrexia of unknown origin.
AB  - Pyrexia of unknown origin (PUO) is defined as fever above 38.5 degrees C lasting
      for 3 weeks, of which at least 1 week has been spent in thorough investigation
      without a conclusive cause. Tuberculosis remains an important cause of PUO,
      particularly with the rising incidence of human immunodeficiency virus infection.
      It may strike virtually any organ in the body and can even mimic metastases
      especially in a known treated case of carcinoma. Bacterial infections, human
      immunodeficiency virus, hidden malignancy, sarcoidosis, and autoimmune disorders
      are some other important causes of PUO. Initial investigations include
      examination of blood, urine, stool, blood biochemistry, culture, etc. Typical
      radiologic investigations include chest radiography, computed tomography, and
      magnetic resonance imaging. Presented here is an atlas of cases where these
      investigations had been inconclusive but fluorine-18 fluorodeoxyglucose positron
      emission tomography/computed tomography demonstrated the site of pathology and
      directed histologic diagnosis.

PMID- 21716007
TI  - Pulmonary artery sarcoma detected on F-18 FDG PET/CT as origin of multiple spinal
      metastases.
AB  - A 67-year-old man with back pain was diagnosed as having multiple spinal
      metastases on MRI. On CT scan, only a filling defect in the right pulmonary
      artery was observed and suspected as venous thromboembolism. On F-18
      fluorodeoxyglucose (FDG) PET/CT, intense hypermetabolism was observed in the
      right pulmonary artery in addition to the metastatic spine lesions. Biopsy
      confirmed the lesion as a primary pulmonary artery sarcoma (PAS), and the spine
      lesions as metastases of PAS. Although PAS is rare and its bone metastasis
      presenting initial symptom is extremely rare, FDG PET/CT is an effective
      diagnostic modality for PAS, not only in discrimination from venous
      thromboembolism, but also in workup of metastatic origin.

PMID- 21716008
TI  - Extramedullary gastric relapse of acute lymphoblastic leukemia following
      allogeneic stem cell transplant: staging with F-18 FDG PET/CT.
AB  - A 26-year-old man with a prior history of acute leukemia that was treated with a
      stem cell transplant (SCT) was referred for an F-18 FDG PET/CT to assess
      suspicious new gastric mucosal lesions. The lesions were FDG-avid and were
      histologically proven to be acute lymphoblastic leukemia (ALL). Extramedullary
      relapse of ALL after SCT is very rare, with only 60 cases reported in the
      literature, and the role of F-18 FDG PET/CT in monitoring for ALL relapse
      following SCT has not been previously investigated. This rare case report
      highlights the use of F-18 FDG PET/CT in staging gastric relapse of ALL following
      SCT.

PMID- 21716009
TI  - A predominant pelvic gastrointestinal stromal tumor (GIST) mass observed on Tc
      99m red blood cell gastrointestinal bleeding scintigraphy.
AB  - A 51-year-old woman presented with recurrent bleeding per rectum. Her earlier
      endoscopies were negative. Tc-99m RBC GI bleeding scintigraphy was performed. It
      demonstrated an apparent hypervascular pelvic mass, and active small bowel
      bleeding. Based on scintigraphic finding of a predominant pelvic mass indicating
      tumor, CT of the abdomen and pelvis was performed for further gastrointestinal
      bleeding localization work up instead of an invasive angiography or endoscopy,
      which detected a small bowel tumor in the pelvis. A small bowel gastrointestinal
      stromal tumor was resected subsequently.

PMID- 21716010
TI  - A unique finding on gallium-67 scintigraphy: widespread fatal skin manifestations
      of Pseudomonas sepsis.
AB  - We report a case of a 25-year-old woman presented with neutropenic fever after
      chemotherapy for the relapse of acute biphenotypic leukemia. Gallium-67
      scintigraphy for the detection of infectious foci demonstrated a unique pattern
      of numerous foci with intense and varying-sized radioactivity spreading
      throughout the body. The subsequent skin biopsy and culture proved Pseudomonas
      infection. Therefore, this unique image, in combination with clinical
      information, was compatible with cutaneous manifestations of Pseudomonas sepsis.
      Eventually, the patient died of uncontrolled systemic infection despite the
      aggressive antibiotic treatment. This case reminded clinicians and nuclear
      medicine physicians to notice the potentially fatal finding on gallium-67 scan.

PMID- 21716011
TI  - Collision lung cancer on F-18 FDG PET/CT.
AB  - We report a case of a primary collision lung cancer consisting of squamous cell
      carcinoma and adenocarcinoma. A 73-year-old man with an abnormality found on
      chest radiograph in the right lower lobe was examined by FDG PET/CT (F-18
      fluorodeoxyglucose positron emission tomography/computed tomography). The tumor
      was composed of 2 different morphologic and FDG accumulation portions and a
      collision tumor was suspected. Histopathologically, this tumor was composed of
      squamous cell carcinoma and adenocarcinoma. Each element was clearly
      distinguished but touched. FDG PET/CT is a useful tool to diagnose collision
      tumor as it shows morphologic and metabolic differences between 2 distinct tumor
      components.

PMID- 21716012
TI  - Comparison of C-11 methionine and C-11 choline for PET imaging of brain
      metastases: a prospective pilot study.
AB  - PURPOSE: The aim of the study was the comparison of C-11 methionine (MET) and C
      11 choline (CHO) in the positron emission tomography (PET) imaging of brain
      metastases in correlation to the histopathology findings in stereotactic biopsy.
      METHODS: In all, 8 patients underwent MET and CHO PET and magnetic resonance
      imaging, in 7 of these, the metastases were previously treated by radiation
      therapy. Histopathologic diagnosis was made for each patient by frame-based
      stereotactic serial biopsy. Standardized uptake values of tumor uptake and lesion
      to-normal brain tissue ratios (LNRs) of the lesions were determined. LNRs for
      each tracer were compared with the histopathology findings and follow-up.
      RESULTS: In 6 patients, biopsy revealed viable metastases, 1 patient suffered
      from tumor recurrence in follow-up and 1 patient was tumor free in biopsy and
      follow-up. In the last mentioned patient, LNR was the lowest determined in all
      patients for CHO, but not for MET. Mean standardized uptake values of the lesions
      were in median 1.8 for MET and 1.1 for CHO, median LNRs were 1.5 for MET and 6.6
      for CHO. LNRs for CHO were significant higher than those for MET (P = 0.007).
      CONCLUSIONS: In the direct comparison to the well-established amino acid tracer
      MET, CHO seems to be promising for the imaging of brain metastases because of
      significantly higher LNRs in tumor tissue compared with MET without evidence for
      a lower specificity of CHO uptake.

PMID- 21716013
TI  - Regional cerebral blood flow abnormalities in patients with kawasaki disease.
AB  - PURPOSE: Kawasaki disease (KD) is an acute febrile disorder of unknown etiology.
      Brain single-photon emission computed tomography (SPECT) and magnetic resonance
      imaging (MRI) help in detecting regional cerebral blood flow abnormalities and
      brain damage. The usefulness of SPECT and MRI in patients with KD was evaluated.
      MATERIALS AND METHODS: All 22 patients with KD underwent brain SPECT using Tc-99m
      hexamethyl propylene amine oxime from 6 days to 3 years after onset, and 8
      patients underwent brain MRI. Of the 22 patients, 4 had neurologic symptoms. Case
      1 showed prolonged apnea; case 2, prolonged disturbance of consciousness; and
      cases 3 and 4 generalized tonic-clonic seizures. Initial brain SPECT showed
      localized hypoperfusion in 4 and 13 patients with and without neurologic
      symptoms, respectively. RESULTS: All patients with neurologic symptoms underwent
      follow-up SPECT; localized hypoperfusion was detected between 1- and 6-month
      follow-up in 3 of these patients. Six patients without neurologic symptoms
      underwent follow-up SPECT. Localized hypoperfusion was detected at approximately
      1- to 11-month follow-up in 4 of these patients. Diffusion-weighted imaging
      revealed abnormal high-intensity areas in the corpus callosum in case 1. Case 2
      showed a bilateral chronic subdural hematoma with decreased size and ischemic
      changes, and case 3 showed bilateral hippocampal atrophy and left hippocampal
      sclerosis. CONCLUSIONS: Because the occurrence of localized hypoperfusion is
      possibly not restricted to only the acute phase in KD, brain SPECT and MRI should
      also be performed in KD patients with neurologic symptoms.

PMID- 21716014
TI  - Detection of recurrence in glioma: a comparative prospective study between Tc-99m
      GHA SPECT and F-18 FDG PET/CT.
AB  - BACKGROUND: Early and correct diagnosis of tumor recurrence and its
      differentiation from therapy-related changes is crucial for prompt and adequate
      management of glioma patients. The purpose of this study was to compare the
      efficacies of Tc-99m glucoheptonate (GHA) single photon emission tomography
      (SPECT) and F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed
      tomography (PET/CT) in detection of recurrence in patients with glioma. METHODS:
      A total of 90 patients with histopathologically proven glioma who had suspicion
      of recurrence clinically or on magnetic resonance imaging were evaluated using Tc
      99m GHA SPECT and FDG PET/CT. Combination of clinical follow-up, repeat imaging,
      and biopsy (when available) was taken as gold standard. RESULTS: On the basis of
      gold standard, 59 patients were positive and 31 were negative for tumor
      recurrence. The sensitivity, specificity, and accuracy of GHA SPECT were 85%,
      97%, and 89%, respectively, whereas those of FDG PET/CT were 70%, 97%, and 80%,
      respectively. On subgroup analysis, GHA SPECT performed better than FDG PET/CT in
      all grades except for grade II gliomas, where both were equally effective. In
      all, 15 patients had intermodality discordance, with GHA SPECT being correct in
      13 of them. CONCLUSIONS: GHA SPECT appears to be a better imaging modality than
      FDG PET/CT for detection of recurrent gliomas.

PMID- 21716015
TI  - Attention deficit/hyperactivity disorder: is there a correlation between dopamine
      transporter density and cerebral blood flow?
AB  - Attention deficit/hyperactivity disorder (ADHD) is one of the most frequent
      behavioral problems in school-age children. Although the etiology remains
      unclear, the involvement of the dopaminergic system has been suggested by genetic
      studies that report an overexpression of the dopamine transporter (DAT) gene. In
      spite of these abnormalities being directly related to the decrease of dopamine
      (DA) in the striatum (STR), abnormalities in brain perfusion have also been
      observed in cortical-subcortical structures. Functional neuroimaging studies have
      suggested that the DA concentration may cause changes in the cerebral blood flow
      (CBF). The objective of our study was to evaluate the relationship between DAT
      density in STR and cortical-subcortical impairment in CBF. Based on the
      hypothesis that there is a correlation between DA availability and brain
      perfusion, we postulated that individuals with ADHD, with a higher DAT density in
      the basal ganglia, will have lower perfusion in the fronto-striatal-cerebellar
      networks. We used Tc-99m TRODAT-1 SPECT to measure DAT density and Tc-99m ECD
      SPECT to assess brain perfusion. Ten adolescents diagnosed with ADHD by
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria
      were investigated. Analysis with Statistical Parametric Mapping 5 corrected for
      multiple comparisons, using small volume correction, showed a significant
      negative correlation between the DAT density in the STR and CBF in the cingulate
      gyrus, frontal lobe, temporal lobe, and cerebellum (pFDR <0.01). Our findings
      suggest that higher DAT density in the STR was associated with a decrease in the
      regional CBF in the cortical and subcortical attention network.

PMID- 21716016
TI  - Kikuchi-Fujimoto disease: PET/CT assessment of a rare cause of cervical
      lymphadenopathy.
AB  - PURPOSE: Kikuchi-Fujimoto disease (KFD), formerly called subacute necrotizing
      lymphadenitis, is a rare cause of cervical lymphadenopathy. The purpose of this
      study was to evaluate the usefulness of FDG PET/CT for distinguishing KFD from
      non-Hodgkin lymphoma (NHL). MATERIALS AND METHODS: Twenty-two patients with
      cervical lymphadenopathy (8 with KFD and 14 with NHL) underwent CT and FDG PET/CT
      scans to examine the cervical lymphadenopathy. Regional values of FDG uptake were
      evaluated using the standardized uptake value (SUV) and partial volume corrected
      SUV (corSUV) based on the count recovery coefficient. Tumor size (mm), SUV, and
      corSUV were compared among KFD, indolent NHL, and aggressive NHL. RESULTS: KFD
      lesions tended to be smaller (13.8 +/- 5.4 mm) than those of indolent (25.4 +/-
      11.8) and aggressive (29.7 +/- 18.8) NHL, whereas there were no significant
      differences in size. As for SUV, a significant difference was observed only
      between indolent and aggressive (6.4 +/- 1.5 and 17.3 +/- 9.3, P < 0.05) NHL;
      however, KFD showed a significantly greater corSUV (23.8 +/- 10.6) as compared
      with indolent NHL (9.2 +/- 5.1, P < 0.05), which did not show a significant
      difference from aggressive NHL (21.4 +/- 10.2). FDG PET/CT detected
      thoracoabdominal lesions in 2 patients (25%) with KFD. CONCLUSIONS: KFD shows
      high FDG uptake for size, which may reflect the pathologic characteristics,
      including necrotizing lymphocytes and numerous histiocytes (macrophages)
      surrounding small necrotic foci. FDG PET/CT will be useful for detecting
      noncervical lesions of KFD and distinguishing KFD from NHLs using both SUV and
      corSUV.

PMID- 21716017
TI  - CT nonuniform attenuation and TEW scatter corrections in brain Tc-99m ECD SPECT.
AB  - Perfusion brain single photon emission computed tomography (SPECT) is currently
      used to evaluate patients with cognitive impairments. Although widely available,
      it has been reported to be significantly less sensitive than F-18 FDG positron
      emission tomography. Optimization of SPECT parameters using nonuniform
      attenuation correction (NUAC) and scatter correction (SC) might improve the
      accuracy of the method. This study assessed the effect of x-ray CT-based NUAC and
      triple-energy window (TEW-SC) on brain SPECT compared with Chang-uniform (UAC). A
      total of 31 patients with memory complaints underwent Tc-99m ECD SPECT/CT. CT
      NUAC+TEW-SC and Chang-UAC were applied and compared. The images were spatially
      normalized to a default SPECT template supplied with Statistical Parametric
      Mapping software (SPM2). A paired t test image was then reconstructed. Regional
      cerebral blood flow measurements were apparently reduced in the frontal white
      matter and in the frontotemporal cortex when CT-NUAC+TEW-SC were used. These
      findings need to be considered when interpreting Tc-99m ECD SPECT after applying
      CT-AC+TEW-SC. Further prospective studies with clinical correlations are needed.

PMID- 21716018
TI  - Two sequential Tc-99m ECD SPECT studies in a case of sporadic Creutzfeldt-Jakob
      disease confirmed at autopsy.
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a subacute spongiform
      encephalopathy characterized by rapidly progressive dementia, hard to diagnose
      during life. MATERIALS AND METHODS: We present a case of a patient with
      pathologically confirmed sporadic form of CJD in whom initial diagnostic tests
      were negative. Two sequential brain single-photon emission computed tomography
      with Tc-99m ethyl-cysteinate dimer were performed, the first one was performed
      few days after the admission into hospital and the second, 1 month later.
      RESULTS: Both studies revealed a decrease in regional cerebral blood flow
      indicative of neuronal dysfunction, more pronounced in the second study.
      CONCLUSION: Current radionuclide scintigraphy can be an useful tool for the
      investigation of CJD.

PMID- 21716019
TI  - Additional Benefit of F-18 FDG PET/CT in the staging and follow-up of pediatric
      rhabdomyosarcoma.
AB  - PURPOSE: The therapeutic management of rhabdomyosarcoma (RMS) is strongly
      dependent on initial staging. This study aimed to evaluate F-18
      fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography
      (CT) as an adjunct to conventional imaging (CI) in the staging and follow-up of
      pediatric RMS. MATERIALS AND METHODS: A total of 13 consecutive children and
      adolescents (12 males, 1 female; mean age, 9.6 years) with histologically proven
      RMS (10 alveolar, 3 embryonal), in whom FDG PET/CT was performed at staging and
      follow-up, were retrospectively included. In total, 35 FDG PET/CT were compared
      with CI (MRI, CT, and bone scintigraphy) performed with a less than a 15-day
      interval. Histologic data, follow-up (mean, 27 months), and the final judgment of
      a multidisciplinary tumor board were considered as the standard of reference for
      result interpretation. RESULTS: At staging, FDG PET/CT revealed 1 RMS of the
      prostate missed by CI, and found 19 true-positive lymph node territories in 4
      patients and 11 bone metastases in 3 patients, versus 12 and 3, respectively,
      with CI. Conversely, FDG PET/CT was less sensitive for detecting infracentimetric
      lung nodules in 1 patient. On the whole analysis, FDG PET/CT modified lymph node
      staging in 4 of 13 patients, bone involvement in 2 patients, and led to treatment
      alteration in 2 children. CONCLUSIONS: FDG PET/CT can be useful in staging and
      restaging pediatric RMS, especially for assessing lymph nodes and bone
      involvement, and for detecting unknown primary sites of RMS, with potential
      therapeutic strategy alteration.

PMID- 21716020
TI  - Is lymph node metastasis a common feature of gastrointestinal stromal tumor?
      PET/CT correlation.
AB  - PURPOSE: We investigated the incidence of lymph node metastasis in
      gastrointestinal stromal tumor (GIST) patients in our PET/CT database. The
      demographic data and characteristics of the primary tumor were evaluated in GIST
      patients with or without lymph node metastasis. MATERIALS AND METHODS: We
      reviewed our PET/CT database from January 1, 2007 to November 30, 2010 by using
      keyword search, and identified GIST with lymph node metastasis according to our
      standard of reference. Statistical analysis was conducted between GIST group with
      or without lymph node metastasis based on the age, sex, primary tumor size, and
      primary tumor location. RESULTS: A total of 29 GIST patients were found in our
      database. Six of them had lymph node metastasis, corresponding to 20.7%. When
      considering only the adult patients, the incidence was 17% (5 out of 28). There
      were 4 males and 1 female, with the mean age of 66.8 years old, which was 8 years
      older than the group without lymph node metastasis. Of the 5 adult metastasis
      patients, 4 had their primary tumor located at very rare sites other than stomach
      or small bowel. Statistical analysis using Fisher exact test of rare location
      showed significance between the 2 groups with P = 0.004. The mean size of the
      primary tumor in the group with lymph node metastasis was 5.2 cm, which was 2.9
      cm less than the group without metastasis. No statistical significance was found
      in age, sex, or size of primary tumor between the 2 groups. CONCLUSION: The
      incidence of lymph node metastasis in GISTs in our database is 20.7%, which is
      surprisingly higher than we thought from other previous studies. In contrast to
      the group without lymph node metastasis, these patients tend to be of older ages
      and had rare location of the primary tumor. This result supports further study
      with larger sample size.

PMID- 21716021
TI  - The value of imaging in standing position in preoperative breast
      lymphoscintigraphy.
AB  - PURPOSE: Breast lymphoscintigraphy is an accurate technique, but in a minority of
      cases the sentinel node (SN) visualization cannot be achieved or can be very
      difficult. We evaluated the potential clinical advantages and limitations of
      performing imaging in the standing position. The aim was to establish if this
      examination modality is quicker and helpful in the presence of "hidden" SN,
      checking also for any influence of SN skin landmarking in the upright position on
      the correct intraoperative SN identification. The overall objective was to verify
      if the standing position can be routinely used in breast lymphoscintigraphy.
      METHODS: A total of 144 patients underwent lymphoscintigraphy in both standing
      and supine positions. In both modalities, a skin landmark was set coincident with
      the SN orthogonal projections. The acquisition times of 2 groups (each consisting
      of 45 patients) examined with the standing or supine acquisition modality, were
      compared. RESULTS: In 6 cases with hidden SN and in 34 cases with difficult or
      partial visualization in one of the supine views, the standing protocol was
      effective and led to better and quicker visualization of lymph nodes (median
      examination time: 25.5 minutes standing, 35.5 minutes supine). Significant
      differences in skin landmark position between the 2 modalities were present only
      in overweight patients and in large breasts. This, however, did not have a
      negative impact on successful intraoperative localization of SN with the gamma
      probe. CONCLUSIONS: Standing acquisition resulted to be a faster, easier, and
      more accurate examination protocol and can be used as the routine method for SN
      detection in breast lymphoscintigraphy.

PMID- 21716022
TI  - Dose-response relationship between cumulative mercury exposure index and specific
      uptake ratio in the striatum on Tc-99m TRODAT SPECT.
AB  - PURPOSE: Tc-99m TRODAT is an agent for dopamine transporters and measuring
      dopamine innervation of the striatum. An association between Parkinson disease
      and body burden mercury level has been reported in the scientific published data.
      The purpose of this study was to investigate the effect of mercury exposure on
      dopamine transporters in the striatum measured by Tc-99m TRODAT single-photon
      emission computed tomography (SPECT). METHOD AND MATERIALS: Study subjects
      included 17 workers who worked in a lamp factory at risk for mercury vapor
      exposure and 15 age-matched healthy controls. All subjects received Tc-99m TRODAT
      SPECT, brain computed tomography scan, and neurologic examinations. Biologic
      urine mercury levels at the end of a work week were assessed for workers.
      RESULTS: There were significant differences in specific uptake ratio (SUR) in the
      striatum, caudate, and putamen between mercury exposure workers and healthy
      controls on Tc-99m TRODAT SPECT (all P < 0.001). The results showed a
      significantly negative correlation between urine and cumulative mercury levels
      and SUR in the striatum on Tc-99m TRODAT SPECT by Pearson analysis (r = -0.501, P
      = 0.040; r = -0.563, P = 0.019). After adjusting for age, gender, and body mass
      index, cumulative mercury exposure index (Cum Hg) was demonstrated to be the
      statistically significant predictor for SUR in the striatum, caudate, and putamen
      on Tc-99m TRODAT SPECT by multiple linear regression analysis (beta = -0.543, P =
      0.018; beta = -0.521, P = 0.033; beta = -0.465, P = 0.048). CONCLUSION: Mercury
      exposure has significantly negative effect on dopamine transporters in the
      striatum. There is dose-response relationship between cumulative mercury exposure
      index (Cum Hg) and SUR in the striatum on Tc-99m TRODAT brain SPECT.

PMID- 21716023
TI  - Tips for leaders, part I: basic principles of leadership.
AB  - There are many important leadership skills that can be learned from experience,
      mentoring, reading, discussions, lectures, etc. The subjects include not only
      business topics and communication skills but also a variety of tips on what to do
      and what not to do. These include desirable styles of leadership, how to gain the
      trust of others in the organization, the significance of the appropriate
      delegation of tasks, the importance of teams, how to manage change, how to win
      during a crisis, what to do in the early days of becoming a new leader,
      preventing the loss of one's practice to a rival organization, improving quality,
      and others. There are also many important attributes of leaders, including having
      a strong moral compass. Although each of these topics could be a book in of
      itself, this short series of articles will briefly examine these issues and
      others.

PMID- 21716024
TI  - An unusual muscular metastasis in a patient affected by ileal carcinoid imaged
      with a 111In-Pentetreotide SPECT/CT scan and confirmed by biopsy.
AB  - 111In-Pentetreotide SPECT/CT scan has been widely validated in diagnosis and
      follow-up of carcinoid and other neuroendocrine tumors. A 70-year-old man, who
      underwent an ileal resection for carcinoid 5 years ago, came to our observation
      during follow-up. We performed a In-DTPA-Pentetreotide (150 MBq) SPECT/CT scan.
      Images taken after 2 hours showed a focal, pathologic uptake on the left leg,
      confirmed at later acquisitions. Lateral projection showed that the uptake area
      was located in a leg muscle; the lesion was confirmed as an intramuscular
      metastasis by biopsy. Intramuscular metastasis of carcinoid tumors is an
      extremely rare manifestation, particularly if not adjacent to the primary tumor,
      because the muscle is a very uncommon location of hematogenous metastases.

PMID- 21716025
TI  - Images of a case of Carney triad by combined F-18 FDG PET/CT.
AB  - Carney triad is a very rare condition with gastrointestinal stromal tumor,
      pulmonary chondroma, and extra-adrenal paragangliomas. We present the images of a
      patient with the complete triad, including total gastrectomy for gastrointestinal
      stromal tumor at the age of 13, and a left pneumonectomy for pulmonary chondroma
      at the age of 15. Results of F-18 FDG PET/CT that was performed at age of 22 for
      recurrent pulmonary chondroma also demonstrated new lesions in the neck,
      mediastinum, and abdomen representing extra-adrenal paragangliomas.

PMID- 21716026
TI  - Oncocytoma of the parotid gland causing false-positive result on I-131 whole-body
      scintigraphy.
AB  - A 50-year-old patient underwent near-total thyroidectomy in 1997 because of a
      T1N0M0 follicular carcinoma in the right lobe of the thyroid gland, followed by I
      131 ablation (3700 MBq). Follow-up of I-131 whole-body scintigraphy after 9 years
      showed pathologic uptake at the left side of the neck. Histopathologic analyses
      of the resected specimen suggested a cystic metastasis within the parotid gland,
      probably originating from thyroid carcinoma. However, the patient had been
      disease-free for over 9 years and thyroglobulin was undetectable in plasma.
      Revision of the specimen with complementary immunohistochemical staining revealed
      histopathologic aspects more typical of oncocytoma.

PMID- 21716027
TI  - Erdheim-Chester disease: imaging-guided therapeutic approach.
AB  - Erdheim-Chester disease (ECD) is a rare form of systemic non-Langerhans cell
      histiocytosis with characteristic bone involvement. However, extraskeletal
      involvement occurs in approximately half of the patients. Because of its protean
      findings, the diagnosis of ECD is often delayed; thus, a clinical suspicion may
      prompt specific imaging studies to recognize suggestive signs of organ
      involvement. In this study, a case of a patient with ECD with representative
      progressive multisystemic involvement has been reported; although the final
      diagnosis was confirmed by histologic analysis, imaging studies with almost
      pathognomonic findings guided the diagnostic process and prompted different
      therapeutic approaches according to the localization of the disease.

PMID- 21716028
TI  - Diagnosis of synchronous isolated splenic metastasis from lung adenocarcinoma:
      complementary role of FDG PET/CT and diffusion-weighted MRI.
AB  - Isolated splenic metastasis is extremely rare. In this study, we report a case of
      a 52-year-old man referred for Pancoast Tobias Syndrome by which FDG PET/CT
      detected an isolated splenic metastasis. Diffusion-weighted MRI confirmed the
      isolated splenic lesion. A low apparent diffusion coefficient was consistent with
      a tumor lesion. CT-guided biopsy of both the lesions and histopathologic findings
      confirmed a lung adenocarcinoma with an isolated splenic metastasis. This case
      reveals a very rare occurrence of isolated splenic metastases in the context of
      lung cancer and illustrates the role of multimodality functional imaging for the
      early detection of uncommon metastasis.

PMID- 21716029
TI  - Unilateral agenesis of the parotid gland with contralateral compensation
      hypermetabolism of FDG.
AB  - A 75-year-old man with prostate adenocarcinoma had a baseline FDG PET/CT that
      demonstrated increased left parotid and absent right parotid activity. The CT
      revealed fat in the right parotid space and enlargement of the left parotid
      gland. There was no history of dry mouth. Agenesis of one or more of the salivary
      glands is extremely rare with only few reported cases. Awareness of anatomic
      variations is helpful for reviewing PET without CT or pertechnetate, sestimibi,
      and gallium examinations where salivary gland activity may typically be
      interpreted without coregistered CT.

PMID- 21716030
TI  - Submandibular salivary gland transfer: a pitfall in head and neck imaging with F
      18 FDG PET/CT.
AB  - Xerostomia is a significant morbidity of radiation treatment in the management of
      head and neck cancers. To preserve salivary function, a surgical technique has
      been developed that involves the transfer of one submandibular gland to the
      ipsilateral submental space, where it can be shielded during radiation therapy. F
      18 FDG PET/CT imaging characteristics of recently or remotely transferred
      submandibular glands have not been previously described in the literature. We
      report 2 cases of patients with surgically transferred submandibular glands,
      which highlight a potential pitfall in the interpretation of PET/CT of the head
      and neck region in oncologic patients.

PMID- 21716031
TI  - False-positive PET/CT for lymphoma recurrence secondary to Langerhans cell
      histiocytosis.
AB  - A 28-year-old man with a history of Hodgkin lymphoma that was intensely [F
      18]fluoro-2-deoxy-D-glucose-avid at diagnosis had achieved complete remission
      following appropriate therapy. On surveillance positron emission
      tomography/computed tomography (CT), new, intensely [F-18]fluoro-2-deoxy-D
      glucose-avid lesions (lytic on CT) were seen within the vertebral body of C7,
      left scapula, and right glenoid. The findings of a biopsy revealed these lesions
      to be Langerhans cell histiocytosis. Langerhans cell histiocytosis arising in the
      context of lymphoma is a well-documented phenomenon, and its appearance on
      positron emission tomography/CT cannot be conclusively distinguished from
      lymphoma recurrence. This manuscript emphasizes the necessity of biopsy to ensure
      correct diagnosis and subsequent correct therapy.

PMID- 21716032
TI  - Incidental detection of unsuspected pulmonary embolism on oncologic FDG PET/CT
      imaging.
AB  - Incidental findings are not infrequent on integrated FDG PET/CT scans by the
      virtue of obtaining images from skull base to mid thigh. These can be on the FDG
      PET portion or the CT portion of the study and can be clinically significant. We
      report a case of FDG PET/CT imaging performed for staging of head and neck cancer
      that led to the detection of unsuspected pulmonary embolism. Our case reinforces
      the importance of careful interpretation of incidental findings on FDG PET/CT
      imaging as they can have a significant effect on patient management.

PMID- 21716033
TI  - Tracheobronchial FDG uptake in primary amyloidosis detected by PET/CT.
AB  - Tracheobronchial amyloidosis is a rare manifestation of the disease and has never
      been described with FDG PET/CT. In this study, we report a case of a 70-year-old
      man with increasing dyspnea, a right pleural effusion, a tracheobronchial
      circumferential wall thickening, and a mediastinal fat infiltration on CT scan.
      FDG PET/CT revealed intense tracheobronchial uptake associated with mediastinal
      and intra-abdominal fat uptake. Bronchoscopy and mediastinoscopy with biopsies
      confirmed the diagnosis of primary amyloidosis and excluded malignancy. FDG
      PET/CT could be useful for the evaluation of tracheobronchial amyloidosis
      metabolic activity and follow-up.

PMID- 21716034
TI  - Cerebral hypermetabolism demonstrated by FDG PET in familial Creutzfeldt-Jakob
      disease.
AB  - Right cerebral and contralateral cerebellar hypermetabolism were observed on FDG
      PET in a 68-year-old woman with familial Creutzfeldt-Jakob disease (CJD) at an
      early stage before seizures occurred. The disease progressed with frequent
      seizures, myoclonus, and a startle reaction. In all past reports, FDG PET studies
      demonstrated hypometabolism in the cerebrum, cerebellum, and thalamus in patients
      with CJD. Focal hypermetabolism corresponding with epileptic foci is a common
      finding in ictal epilepsy patients, and hypometabolism is common in patients with
      myoclonus or the startle reaction. This finding may reflect a prodromal
      pathophysiology of epilepsy. Attention should be paid to the diagnosis of CJD
      while using FDG PET.

PMID- 21716035
TI  - Imaging identifies submandibular ectopic thyroid tissue.
AB  - The identification of submandibular ectopic normal thyroid in the lateral neck
      with a coexisting normally located and functional thyroid gland is rare. Ectopic
      normal thyroid tissue in the midline location is most commonly related to
      aberrant migration along the thyroglossal duct (ie, lingual thyroid). A 54-year
      old man with a 6-month history of visible asymptomatic swelling in the right
      submandibular region had ultrasonography and Tc-99m pertechnetate imaging.

PMID- 21716036
TI  - Pituitary FDG uptake in a patient of lung cancer with bilateral adrenal
      metastases causing adrenal cortical insufficiency.
AB  - A 64-year-old woman with history of lung cancer and left adrenal gland metastasis
      was referred for FDG PET/CT to assess the response to target therapy and local
      radiotherapy treatment. In addition to bilateral adrenal gland FDG uptake
      lesions, the PET/CT also showed focal FDG uptake in pituitary gland with
      standardized uptake value of 3.9. Adrenocorticotropic hormone serum level was 439
      pg/mL (normal <46 pg/mL), and serum cortisol level was 6 MUg/dL (normal range, 5
      25 MUg/dL). The image and serum test results suggested the diagnosis of lung
      cancer, with bilateral adrenal metastases causing adrenal cortical insufficiency
      with secondary pituitary gland hyperplasia.

PMID- 21716037
TI  - Recurrent ovarian carcinoma presenting as a solitary sternal metastasis on FDG
      PET/CT.
AB  - We report the positron emission tomography/computed tomography appearance of
      solitary sternal metastasis from primary ovarian carcinoma in a 65-year-old woman
      who underwent surgery followed by chemoradiation treatment 3 years earlier.
      Restaging positron emission tomography/computed tomography study demonstrates an
      intensely active destructive lesion involving the entire sternum (maximum
      standard uptake value: 4.7) with a photopenic soft tissue mass component in the
      center of the sternum protruding anteriorly suggestive of necrosis. This sternal
      lesion was subsequently biopsied and pathology revealed metastatic disease from
      the primary ovarian tumor for which the patient had received chemoradiation
      therapy. Bone involvement in ovarian cancer is relatively rare and even rarer in
      the sternum.

PMID- 21716038
TI  - Current readings in nuclear medicine.

PMID- 21716039
TI  - Chronic care management and quality, the International Council of Nurses (ICN)
      meeting in Malta, and an International Home Care Nurses Organization (IHCNO)
      poster!

PMID- 21716041
TI  - Home care in Kanye, Botswana.

PMID- 21716042
TI  - The use of nurses in community palliative care.
AB  - This qualitative study uses a phenomenological life world perspective to examine
      the utilization of nurses in community palliative care for people with noncancer
      conditions with a life expectancy of 2 years. Sited in Otago, New Zealand, while
      there was a number of health professionals involved in providing palliative care
      in the community for people with malignant conditions, none of the participants
      with nonmalignant disease were receiving specialist palliative care at the time
      of interview. Support services used a rehabilitative model of care that was not
      always appropriate in meeting the needs of the people who were dying and their
      families.

PMID- 21716043
TI  - Depression care for patients at home (Depression CAREPATH): intervention
      development and implementation, part 1.

PMID- 21716045
TI  - Say goodbye to wet-to-dry wound care dressings: changing the culture of wound
      care management within your agency.

PMID- 21716047
TI  - Supporting community caregiving for a spouse with dementia: research with
      implications for practice.

PMID- 21716048
TI  - Care plus: an alternative to traditional patient-centered medical homes.

PMID- 21716049
TI  - Factors influencing persistence or recurrence of cervical intraepithelial
      neoplasia after loop electrosurgical excision procedure.
AB  - OBJECTIVE: The purpose of this study was to determine the predictors of
      persistent or recurrent cervical intraepithelial neoplasia (CIN) after a loop
      electrosurgical excision procedure (LEEP) procedure in an urban population of low
      socioeconomic status. METHODS: A database was created using information about
      LEEPs done between October 2004 and December 2008 at John H. Stroger Jr.
      Hospital, Cook County. This information was then analyzed using chi2 test to
      determine the predictors of persistent or recurrent CIN. RESULTS: A total of 769
      LEEPs were performed during the study period, and 52 were excluded secondary to
      ineligible entries, index cytology report not recorded, or incorrect medical
      record numbers. Persistent or recurrent disease was defined as cytology of
      atypical squamous cells cannot rule out high grade lesion (ASC-H) or worse
      without a histology, or histology of CIN 1 or worse, at any time after the LEEP
      was performed. Of our study population, 64.7% had a follow-up cytology or biopsy
      performed. Of these women, 24.7% had persistent or recurrent disease. The
      preoperative factors, namely positive human immunodeficiency virus serostatus (p
      < .0001) and a preoperative endocervical curettage that was positive for
      neoplasia (p < .0001), and postoperative factors, namely positive margin status
      (p < .0001) and high-grade pathology on the LEEP specimen (p < .0001), were
      significantly associated with persistent or recurrent disease. A high-grade
      preoperative cytology, a high-grade preoperative cervical biopsy, or the type of
      procedure performed (single specimen or separate endocervical pass) was not
      significantly associated with persistent or recurrent disease. CONCLUSIONS: In
      our population, adherence with follow-up was poor, and the rate of persistence or
      recurrence was high. In a limited resource setting such as ours, patients with
      significant predictors of persistence/recurrence such as human immunodeficiency
      virus seropositivity, endocervical disease, and high-grade pathology or positive
      margins on LEEP specimens should be targeted for closer surveillance.

PMID- 21716050
TI  - Differences in cervical cytologic and histologic findings between women using
      depot-medroxyprogesterone acetate and oral contraceptives.
AB  - OBJECTIVE: This study aimed to compare cervical cytologic and histologic findings
      between women using depot-medroxyprogesterone acetate (DMPA) and oral
      contraceptives (OCs) referred for colposcopy and to determine whether there were
      differences in the occurrence of false-positive cytologic finding between the 2
      contraceptive groups. MATERIALS AND METHODS: Retrospective cohort of 1,569
      premenopausal women using either DMPA or OC who were evaluated for abnormal
      cervical cytologic findings. Cytologic and histologic data were collected in
      conjunction with routine gynecologic examinations or follow-up colposcopic
      evaluations. chi2 tests were used to determine differences in cervical cytologic
      and histologic findings and the proportion of false-positive results across
      contraceptive groups. Nominal logistic regression was used to evaluate the
      association between contraceptive use, cervical, and histologic abnormalities
      while controlling or age and smoking status. RESULTS: The mean age of all
      participants was 23.5 years, with no significant difference between OC (n = 1194)
      and DMPA (n = 375) users. Although there were no differences in the proportion of
      false-positive cytologic results (21.8% overall), DMPA users were more likely to
      smoke (p < .001), have atypical glandular cell (AGC) on referral cytology (p <
      .001), and have histologic confirmation of cervical intraepithelial neoplasia 2,
      3 (p = .004). Users of DMPA remained more likely to have AGC cytology after
      considering smoking status; however, cervical intraepithelial neoplasia 2, 3 was
      found to be associated with smoking status and not use of DMPA. CONCLUSIONS: We
      found no difference in the proportion of false-positive cytologic results between
      DMPA and OC users referred for evaluation of abnormal cytology. Users of DMPA
      were more likely to have AGC, which necessitates a more comprehensive evaluation.

PMID- 21716051
TI  - High-risk HPV DNA testing and HPV-16/18 genotyping: what is the clinical
      application?
AB  - OBJECTIVE: There are currently 2 tests approved for clinical use that
      nonspecifically detect the presence of multiple oncogenic or high-risk human
      papillomavirus (HPV) types. One HPV genotyping test is also available for use
      that specifically detects the presence of high-risk HPV types 16 and 18. The
      purpose of this review was to evaluate the clinical performance of these HPV DNA
      tests and the utility of the tests within current screening recommendations.
      MATERIALS AND METHODS: The sensitivity and specificity of currently available HPV
      DNA tests to detect the presence of precancerous high-grade cervical lesions are
      reviewed. Appropriate test usage is discussed in the context of the natural
      history of HPV infection. RESULTS: Molecular testing for the presence of high
      risk HPV is more sensitive but less specific than cytologic testing for the
      detection of high-grade cervical lesions. Current patient management guidelines
      recommend the use of high-risk HPV DNA testing to triage women 21 years or older
      with equivocal cytology results and in conjunction with cytology for cervical
      screening in women 30 years or older. The HPV-16/18 genotyping test may be used
      in women 30 years or older with negative cytology and positive high-risk HPV DNA
      test results to determine the need for colposcopy. CONCLUSIONS: Although
      infection with high-risk HPV is highly prevalent in adult females, most
      infections are transient and do not require intervention. Clinical application of
      appropriate age-adjusted use of HPV DNA testing and its use in conjunction with
      atypical squamous cells of undetermined significance cytology will avoid
      unnecessary follow-up procedures.

PMID- 21716052
TI  - Aggressive angiomyxoma in the pelvis: an ambiguous tumor of which all
      gynecologists must be aware at pelvic examination.

PMID- 21716053
TI  - Implications of weight-based stigma and self-bias on quality of life among
      individuals with schizophrenia.
AB  - Obesity has been associated with significant stigma and weight-related self-bias
      in community and clinical studies, but these issues have not been studied among
      individuals with schizophrenia. A consecutive series of 70 obese individuals with
      schizophrenia or schizoaffective disorder underwent assessment for perceptions of
      weight-based stigmatization, self-directed weight bias, negative affect,
      medication compliance, and quality of life. The levels of weight-based
      stigmatization and self-bias were compared with levels reported for
      nonpsychiatric overweight/obese samples. Weight measures were unrelated to
      stigma, self-bias, affect, and quality of life. Weight-based stigmatization was
      lower than published levels for nonpsychiatric samples, whereas levels of weight
      based self-bias did not differ. After controlling for negative affect, weight
      based self-bias predicted an additional 11% of the variance in the quality of
      life measure. Individuals with schizophrenia and schizoaffective disorder
      reported weight-based self-bias to the same extent as nonpsychiatric samples
      despite reporting less weight stigma. Weight-based self-bias was associated with
      poorer quality of life after controlling for negative affect.

PMID- 21716054
TI  - Symptoms of posttraumatic stress disorder among urban residents.
AB  - Previous studies indicate a high risk of Posttraumatic Stress Disorder (PTSD)
      among women and low-income, urban-residing African-Americans. This study examined
      PTSD symptoms among urban-residing, socioeconomically diverse, working-age
      African-Americans and whites. The participants completed the PTSD Checklist
      Civilian Version. Of the 2104 participants, 268 (12.7%) were screened positive
      for PTSD symptoms. Women (13.8%) were more likely than men (11.3%), white
      participants (13.8%) were more likely than African-Americans (11.9%), and younger
      participants (16.1%) were more likely than older participants (10.2%) to screen
      positive for PTSD symptoms. A significant interaction (p = 0.05) revealed that
      white women living below the 125% poverty level were most likely to report PTSD
      symptoms. These findings highlight the importance of PTSD screening in low-income
      urban neighborhoods.

PMID- 21716055
TI  - Toxoplasma gondii seropositivity and suicide rates in women.
AB  - Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that infects
      roughly a third of the world population. In an immunocompetent host, infection is
      generally chronic and asymptomatic, as the immune system keeps T. gondii confined
      to cysts and the intracellular space within the muscle and brain. Seropositivity
      has been linked to schizophrenia, car accidents, changes in personality, and more
      recently, suicidal attempts. Very recently, seroprevalence for 20 European
      countries was found to be associated with increased suicide rates. Although
      suicide rates were age-standardized, given that T. gondii seroprevalence
      increases with age and that the blood samples were drawn in women, we now
      retested in women only the association between suicide and T. gondii
      seropositivity, stratified by age. Simple correlations between ranked T. gondii
      seropositivity and suicide rate identified statistically significant
      relationships in women 60 years or older (p < 0.05); adjusting for GDP, the
      statistical significance expanded to include women 45 years and older. The
      strongest association was in the 60- to 74-year-old group where, after adjustment
      for GDP, the relationship (p = 0.007) resisted Bonferroni adjustment for multiple
      comparisons. In conclusion, the results suggest that a positive relationship
      between rates of infection with T. gondii and suicide is apparent in women of
      postmenopausal age. Prospective studies are necessary to further confirm this
      association predictively and to explore mechanisms mediating this relationship.

PMID- 21716056
TI  - Cognition and global assessment of functioning in male and female outpatients
      with schizophrenia spectrum disorders.
AB  - The relationship between the symptom and function subscales of the Global
      Assessment of Functioning (GAF) and neurocognitive test performance was studied
      in 195 outpatients with schizophrenia, schizoaffective disorder, or delusional
      disorder who were assigned to functional groups based on their sex. A composite
      cognition score was created based on z-scores. Stepwise multiple regression
      analysis was used to assess the predictive value of GAF Symptom and GAF Function
      on composite cognition and to check for the effect of the individual cognitive
      tests against the GAF subscales. Better composite cognition scores were predicted
      by higher function levels in male patients and by lower symptom levels in female
      patients. There was also a sex-specific difference in neurocognitive components,
      indicating that executive functioning may have a greater impact on the symptom
      and function profiles of male schizophrenia spectrum patients than on that of
      female patients. The results suggest that endophenotypes in schizophrenia may be
      sex-specific.

PMID- 21716057
TI  - Differential relationship between depression severity and patients' perceived
      family functioning in women versus in men.
AB  - Previous research suggests that depression and family functioning are related and
      that women and men may differ in how they respond to and cope with depression.
      Significantly less attention has been paid to whether sex moderates the
      relationship between family functioning and depression. In the current study, the
      relationship between depression severity and perceived family functioning, both
      generally and in specific areas, was examined in women and men (N = 117)
      hospitalized with major depression. The level of depression severity was not
      significantly different in men and in women. Correlations between depression
      severity and most domains of family functioning were significant and positive for
      men only. Furthermore, sex statistically moderated the associations between
      depression severity and family functioning in the areas of problem solving,
      communication, affective responsiveness, and behavior control. The implications
      for the assessment and treatment of family dysfunction in severely depressed
      patients are discussed.

PMID- 21716058
TI  - Impulsivity in euthymic patients with major depressive disorder: the relation to
      sociodemographic and clinical properties.
AB  - The purpose of this study was to examine the trait impulsivity of patients with a
      major depressive disorder and to explore the possible connections between
      impulsivity and clinical and sociodemographic variables. The sociodemographic and
      clinical properties of 60 patients with major depression, who were euthymic
      according to Hamilton Depression Scale scores, were recorded. Their trait
      impulsivity was evaluated using the Barratt Impulsiveness Scale (BIS-11) and the
      impulsivity subscale of the Temperament and Character Inventory, and the results
      were compared with those of 50 age- and sex-matched healthy controls. We used
      general linear model analysis to evaluate the manner in which the variables
      contributed to BIS-11 scores. Some impulsivity scores were higher in those with a
      major depressive disorder than in comparison subjects. There were significant
      effects of education and sex in these differences. Elevated BIS-11 scores were
      associated with a history of psychotic mood episode and suicide attempts. These
      relationships persisted when age, sex, and education were taken into account.
      These results show that, after accounting for common confounding factors, trait
      like impulsivity was substantially higher in subjects with major depressive
      disorder than in comparison subjects and may be associated with sociodemographic
      and clinical properties.

PMID- 21716059
TI  - Neurocognitive impairments and their relationship with psychosocial functioning
      in euthymic bipolar II disorder.
AB  - The aim of this study was to compare neurocognitive functioning between euthymic
      patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and healthy
      controls. An additional aim was to estimate the relationship between
      neurocognitive impairments and psychosocial functioning. Eighty-seven patients
      with BDI (n = 48) or BDII (n = 39) and 39 healthy controls were included. All
      subjects completed an extensive neurocognitive battery. Psychosocial functioning
      was assessed using the General Assessment of Functioning. Patients with BDII
      performed more poorly than did the controls in measures of psychomotor speed,
      verbal memory, and executive functioning. Patient groups did not show differences
      in any of the cognitive measures assessed. The performance in trail-making test B
      was the only independent predictor of psychosocial functioning in both patient
      groups. Patients with BDII have cognitive impairments, and this has a negative
      influence on their functional outcome. Our results bring additional support to
      the notion that BDII disorder is not a merely mild type of BDI.

PMID- 21716060
TI  - Social cognition moderates the influence of child physical abuse on inpatient
      psychiatric rehabilitation.
AB  - Moderating effects of social cognition in the relationship between the severity
      of history of child physical abuse (CPA) and social functioning were examined
      using 12-month longitudinal data among 143 participants with severe mental
      illness (SMI) in an inpatient psychiatric rehabilitation program. The adverse
      effects of the severity of history of CPA on social functioning were compensated
      for by greater social inference and lower external locus of control.
      Specifically, despite the severity of history of CPA, individuals with intact or
      greater social inference showed greater social functioning than did those with
      lower social inference. The decrease in externality, regardless of the history of
      CPA, seemed to be therapeutic for individuals with SMI. Considering the
      heterogeneity in both SMI and CPA, the current finding sheds light on providing
      trauma-informed, individualized treatment and assessment planning for individuals
      with SMI and a history of CPA.

PMID- 21716061
TI  - Childhood sexual abuse severity and disclosure as predictors of depression among
      adult African-American and Latina women.
AB  - A history of childhood sexual abuse (CSA) has been associated with adult
      depression, but data on abuse severity and disclosure are scant, particularly
      among low-income ethnic minorities. CSA often co-occurs with other adversities,
      which also increase the risk of depression. This study examined the peritrauma
      variable of abuse severity and the posttrauma variables of disclosure and self
      blame as predictors of current depression symptoms in 94 low-income African
      American and Latina women with histories of CSA. After controlling for nonsexual
      childhood adversity and adult burden (i.e., chronic stress), severe CSA overall
      was associated with higher depression scores, especially among Latinas who
      disclosed their abuse. Depression symptoms among African-American women were
      highest in those who disclosed and reported high levels of self-blame at the time
      of the incident. The link between depression and specific peri- and post-CSA
      factors in minority women may help guide future interventions.

PMID- 21716062
TI  - Religious involvement and suicidal behavior among African Americans and Black
      Caribbeans.
AB  - This study explores the relationship between religious denomination, four
      dimensions of religious involvement, and suicidality (lifetime prevalence of
      suicide ideation and attempts) within a nationally representative sample of
      African American and Black Caribbean adults. The relationship between religious
      involvement and suicide for African Americans and Black Caribbeans indicated both
      similarities and differences. For both groups, religious involvement was largely
      protective against suicidal ideation and attempts, although, in some instances,
      specific measures were associated with higher suicidality. Looking to God for
      strength, comfort, and guidance was protective against suicidal attempts and
      ideation, whereas stating that prayer is important in stressful situations was
      associated with higher levels of ideation for both groups and higher attempts
      among Black Caribbeans. For African Americans, reading religious materials was
      positively associated with suicidal ideation. Among Black Caribbeans, subjective
      religiosity was negatively associated with ideation, and being Catholic was
      inversely associated with attempts, whereas being Pentecostal was inversely
      associated with ideation. These findings are discussed in relation to previous
      research and current conceptual frameworks that specify multiple (e.g.,
      prevention and resource mobilization) and often divergent pathways of religious
      effects on physical and mental health outcomes.

PMID- 21716063
TI  - Personality subtypes in adolescent and adult children of alcoholics: a two-part
      study.
AB  - The authors conducted two studies to identify and to validate potential
      personality subtypes in the adolescent and adult children of alcoholics. As part
      of a broader NIMH-funded study, randomly selected psychologists and psychiatrists
      provided personality data on adolescent (n = 208) or adult (n = 349) children of
      alcoholics using a Q-sort procedure (Shedler-Westen Assessment Procedure [SWAP]
      II-A for adolescents and SWAP-II for adults), which were subjected to a cluster
      analytic procedure, Q-factor analysis. Q-factor analysis yielded five personality
      subtypes in both groups. Despite the different samples and age groups, four of
      the personality subtypes were highly similar, including externalizing, inhibited,
      emotionally dysregulated, and high-functioning. Providing initial data on their
      validity, the subtypes differed on axis I and II pathology, adaptive functioning,
      and developmental and family history variables. These findings show heterogeneity
      among children of alcoholics and suggest the importance of addressing personality
      subtypes for research and practice in treating adolescent and adult children of
      alcoholics.

PMID- 21716064
TI  - Effects of acamprosate on cognition in a treatment study of patients with
      schizophrenia spectrum disorders and comorbid alcohol dependence.
AB  - Problems with memory and attention are common to both schizophrenia and alcohol
      dependence. The objectives of this study were to examine the effect of
      acamprosate treatment on cognition and to assess whether the changes in drinking
      patterns or psychotic symptoms were related to changes in cognitive functioning.
      Outpatients with schizophrenia spectrum disorders and alcohol dependence (n = 23)
      were randomized (double-blind) to either acamprosate or placebo treatment for 12
      weeks. Assessments (baseline and week 12) included alcohol use, symptoms of
      psychosis, memory, and attention. The results showed that acamprosate had no
      effect on cognitive functioning and that there was no relationship between change
      in alcohol consumption or psychotic symptoms and change in cognitive functioning
      in this sample of patients. The finding that acamprosate had no negative effects
      on cognition is clinically relevant and reinforces previous reports that
      acamprosate can be used safely for alcohol reduction in this group of patients.

PMID- 21716065
TI  - Alexithymia is common among adolescents with severe disruptive behavior.
AB  - This study aimed to examine alexithymic features and associations between
      alexithymia and psychiatric symptoms among adolescents living in a closed
      institution because of severe behavioral problems. Forty-seven adolescents (29
      boys and 18 girls) aged 15 to 18 years completed the 20-item Toronto Alexithymia
      Scale (TAS-20) Questionnaire and the Youth Self-Report, whereas their foster
      parents completed the Child Behavior Checklist. The TAS-20 scores of the
      participants were compared with those of an extensive population sample (N =
      6000) matched by age and birth year. Reform school adolescents are significantly
      more alexithymic than the control group, and the TAS-20 scores are correlated
      with numerous psychiatric problems, mainly in the internalizing spectrum, but
      also with thought problems and self-reported aggression. Promoting abilities in
      identifying and describing feelings is important when treating delinquent
      adolescents.

PMID- 21716066
TI  - Social disability at admission for a first psychosis does not predict clinical
      outcome at 5-year follow-up.
AB  - Although it has often been reported that premorbid social deficits are associated
      with clinical outcome in schizophrenia, the association between clinical outcome
      and social disabilities during admission for a first psychosis is still unclear.
      We examined whether a detailed assessment of social disability (assessed using
      the Groninger Social Disabilities Schedule-II) in the month before admission for
      a first psychotic episode contributed to the prediction of disease outcome in
      terms of psychopathology in 82 patients with schizophrenia. After controlling for
      the Positive and Negative Syndrome Scale sum score at baseline, none of the
      social disability domains significantly predicted the number of relapses or the
      severity of clinical symptoms at a 5-year follow-up. Our results suggest that
      poor social functioning at admission does not necessarily predict poor disease
      outcome. Following Di Michele and Bolino (Psychopathology 37:98-104, 2004), we
      hypothesize that, to reliably predict the course of schizophrenia, it may be
      necessary to assess social functioning during clinical stabilization.

PMID- 21716067
TI  - Intercorrelations between the Personal and Social Performance Scale, cognitive
      function, and activities of daily living.
AB  - The aim of this study was to evaluate the intercorrelation between the Personal
      and Social Performance (PSP) score, cognitive function, and activities of daily
      living (ADLs). Twenty patients with chronic schizophrenia were recruited; the PSP
      and ADL scales and psychological assessments including the Wisconsin Card Sorting
      Test, the Wechsler Memory Scale-Revised (WMS-R), and the Continuous Performance
      Test (CPT) were administered. Positive correlations between the total PSP scale
      score and performance in the WMS-R, CPT, and ADL scores were identified. The PSP
      score was found to be of good reliability for cognitive function and ADL
      evaluation.

PMID- 21716068
TI  - Minimal invasive anterolateral transthoracic transpleural approach: a novel
      technique for thoracic disc herniation. A review of the literature, description
      of a new surgical technique and experience with first 12 consecutive patients.
AB  - STUDY DESIGN: A retrospective review of a case series. OBJECTIVE: To describe a
      novel surgical technique for a minimally disruptive lateral transthoracic
      transpleural approach to treat thoracic disc herniations. SUMMARY OF BACKGROUND
      DATA: Thoracic disc herniation is a relatively uncommon spinal condition, and
      surgical treatment is indicated for patients with myelopathy or radiculopathy
      that failed to respond to conservative therapy. Presently there is no consensus
      about the best approach to address thoracic disc herniations. Using the novel
      retractor system (MaXcess), the authors describe a novel minimally disruptive
      approach that allows the surgeons to perform a standard anterior discectomy and
      fusion with instrumentation while minimizing approach-related morbidity. METHODS:
      A series of 12 patients with single-level thoracic disc herniations who underwent
      anterior spinal cord decompression followed by instrumented fusion through a
      novel retractor system is being reported. Demographic and radiographic data,
      perioperative complications, and clinical outcomes were reviewed. RESULTS: Twelve
      patients were enrolled with an average age of 51 years (range, 23 to 67 y). The
      average follow-up was 28 months (range, 12 to 33 mo). The average length of
      hospital stay was 5 days (range, 2 to 12 d). The average preoperative visual
      analog scale pain score was 9 (range, 7 to 10), which later decreased to 3
      (range, 0 to 5) at final follow-up. All patients with myelopathy and/or sphincter
      dysfunction had significant improvement of their symptoms. One patient had
      pleural effusion and 1 patient had intercostal neuralgia. CONCLUSIONS: Anterior
      decompression using a transthoracic transpleural approach provides excellent
      exposure and allows consistent decompression of thoracic disc herniations. This
      study demonstrated that a new minimally invasive, transthoracic transpleural
      decompression technique can be safely performed for single-level thoracic disc
      herniations. The early results showed that this technique allows less dissection,
      along with the advantages of conventional thoracotomy.

PMID- 21716069
TI  - Research conceptualization in the global world of nursing research.

PMID- 21716070
TI  - Preexposure prophylaxis and timed intercourse for HIV-discordant couples willing
      to conceive a child.
AB  - Many HIV-discordant couples express a strong wish to conceive a child.
      Insemination with processed semen is offered to these couples in many countries.
      Given the very low level of transmission risk during fully suppressive
      antiretroviral therapy, we offered timed intercourse combined with preexposure
      prophylaxis to further reduce the transmission risk. In 53 cases, natural
      conception was attempted using the proposed method. Pregnancy rates were high and
      reached a plateau of 75% after six cycles. Advanced age in the female partner was
      a predictor for infertility in these couples.

PMID- 21716071
TI  - HIV infection perturbs interleukin-7 signaling at the step of STAT5 nuclear
      relocalization.
AB  - OBJECTIVE: Interleukin-7 (IL-7) responses are impaired in CD4(+) T cells from HIV
      infected patients, which may play a significant role in the loss of CD4(+) T-cell
      homeostasis. We set to investigate the nature of IL-7-dependent signaling defects
      in patients with progressive HIV-1 infection. DESIGN AND METHODS: IL-7 signaling
      was compared in CD4(+) T cells from viremic patients with a viral load more than
      10,000 copies of HIV RNA/ml (n = 23) and from healthy blood donors (n = 23).
      Phosphorylation of the transcription factor STAT5 on the regulatory serine S726
      and the key tyrosine Y694 was monitored by intracellular flow cytometry. Phospho
      STAT5 relocalization to the nucleus was analyzed by quantitative
      immunofluorescence imaging. RESULTS: In control CD4(+) T cells, S726
      phosphorylation was mostly constitutive and inducible by IL-7 to a limited extent
      (1.3x, P < 0.05). In contrast, phosphorylation at Y694 was highly inducible by IL
      7 (12.6x, P < 0.0001). Progressive HIV infection led to hyperphosphorylation of
      both S726 and Y694 in naive CD4(+) T cells, with these changes correlating
      together (R = 0.66, P = 0.01). Quantitative image analysis revealed an impairment
      in the nuclear relocalization of both forms of phospho-STAT5 in patient cells (P
      < 0.005 for S726; P < 0.05 for Y694). The nuclear relocalization defect
      correlated with increased HLA-DR expression (R = 0.75, P < 0.01), suggesting a
      role for chronic immune activation in perturbed IL-7 signal transduction.
      CONCLUSION: HIV infection perturbs IL-7 signaling by impairing the access of
      STAT5 to the nuclear compartment. This defect may contribute to the loss of
      CD4(+) T-cell populations in patients with chronically high immune activation.

PMID- 21716072
TI  - Cervical HIV-1 RNA shedding after cryotherapy among HIV-positive women with
      cervical intraepithelial neoplasia stage 2 or 3.
AB  - OBJECTIVE: To determine the effect of cryotherapy on HIV-1 cervical shedding.
      DESIGN: Prospective cohort study. METHODS: Five hundred HIV-positive women
      enrolled at an HIV treatment clinic in Nairobi, Kenya were screened for cervical
      cancer. Women diagnosed with cervical intraepithelial neoplasia stage 2 or 3 (CIN
      2/3) by histology were offered cryotherapy treatment. The first 50 women had
      cervical swabs taken at baseline and at 2 and 4 weeks following treatment. Swabs
      were analyzed for HIV-1 RNA and compared using General Estimating Equation (GEE)
      with binomial or Gaussian links. RESULTS: Of the 50 women enrolled, 40 were
      receiving antiretroviral therapy (ART) and 10 were not receiving ART at the time
      of cryotherapy and during study follow-up. Among all women, the odds of
      detectable cervical HIV-1 RNA did not increase at 2 weeks [odds ratio (OR) 1.18;
      95% confidence interval (CI) 0.65-2.13] or 4 weeks (OR 1.29; 95% CI 0.71-2.33)
      following cryotherapy. Among 10 women not receiving ART, the OR of detectable
      shedding at 2 weeks was higher, but not statistically significant (OR 4.02; 95%
      CI 0.53-30.79; P = 0.2), and at 4 weeks remained unchanged (OR 1.00; 95% CI 0.27
      3.74). CONCLUSION: There was no increase in detectable cervical HIV-1 RNA among
      HIV-positive women after cryotherapy. The risk of HIV-1 transmission after
      cryotherapy may not be significant, particularly among women already on ART at
      the time of cervical treatment. However, further investigation is needed among
      women not receiving ART.

PMID- 21716073
TI  - Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir
      as 10-day monotherapy in HIV-1-infected adults.
AB  - OBJECTIVE: To evaluate the antiviral activity, safety, pharmacokinetics, and
      pharmacokinetics/pharmacodynamics of dolutegravir (DTG), a next-generation HIV
      integrase inhibitor (INI), as short-term monotherapy. DESIGN: A phase IIa,
      randomized, double-blind, dose-ranging study. METHODS: In this study, INI-naive,
      HIV-1-infected adults currently off antiretroviral therapy were randomized to
      receive DTG (2, 10, or 50 mg) or placebo once daily for 10 days in an eight
      active and two placebo randomization scheme per DTG dose. Placebo patients were
      pooled for the purpose of analysis. RESULTS: Thirty-five patients (n = 9 for DTG
      2 and 10 mg, n = 10 for DTG 50 mg, and n = 7 for placebo) were enrolled. Baseline
      characteristics were similar across dose groups. Significant reductions in plasma
      HIV-1 RNA from baseline to day 11 were observed for all DTG dose groups compared
      with placebo (P < 0.001), with a mean decrease of 1.51-2.46 log(10) copies/ml. In
      addition, a well characterized dose-response relationship was observed for viral
      load decrease. Most patients (seven of 10, 70%) receiving DTG 50 mg achieved
      plasma HIV-1 RNA less than 50 copies/ml. The pharmacokinetic variability was low
      (coefficient of variation, range 25-50%). Plasma HIV-1 RNA reduction was best
      predicted by Ctau using an E(max) model. The most common adverse events were
      diarrhea, fatigue, and headache; the majority of adverse events were mild or
      moderate in severity. CONCLUSION: Dolutegravir demonstrated potent antiviral
      activity, good short-term tolerability, low pharmacokinetic variability, and a
      predictable pharmacokinetics/pharmacodynamics relationship, which support once
      daily dosing without a pharmacokinetic booster in integrase-naive patients in
      future studies.

PMID- 21716074
TI  - Ritonavir-boosted atazanavir exposure is associated with an increased rate of
      renal stones compared with efavirenz, ritonavir-boosted lopinavir and ritonavir
      boosted darunavir.
AB  - There have been no data presented on the relative rates of the development of
      renal stones in those receiving ritonavir-boosted atazanavir (ATZ/r) when
      compared with other commonly used antiretrovirals (ARVs). We compared the rate of
      development of renal stones in a cohort of HIV-infected individuals attending the
      Chelsea and Westminster Hospital Foundation Trust exposed to ATZ/r with those
      exposed to efavirenz (EFV)/ritonavir-boosted lopinavir (LPV/r) and ritonavir
      boosted darunavir (DRV/r) over a 45-month study period. The rate of development
      of renal stones in the ATZ/r group (n = 1206) compared with the EFV/LPV/r/DRV/r
      combined group (n = 4449) was 7.3 [95% confidence interval (CI) 4.7-10.8] per
      1000 patient-years and 1.9 (95% CI 1.2-2.8) per 1000 patient-years (P < 0.001),
      respectively. The renal stones rate remained significantly higher in the ATZ/r
      group after adjusting for prior ATZ/r/indinavir (IND) exposure. When choosing a
      boosted protease inhibitor, ATZ/r renal stones should be considered as a
      potential comorbidity.

PMID- 21716075
TI  - Designing a genome-based HIV incidence assay with high sensitivity and
      specificity.
AB  - OBJECTIVE: Considerable inaccuracy in estimates of HIV incidence has been a
      serious obstacle to the development of efficient HIV/AIDS prevention and
      interventions. Accurately distinguishing recent or incident infections from
      chronic infections enables one to monitor epidemics and evaluate the impact of
      HIV prevention/intervention trials. However, serological testing has not been
      able to realize these promises due to a number of critical limitations. Our study
      is to design a novel scheme of identifying incident infections in a highly
      accurate manner, based on the characteristics of HIV gene diversification within
      an infected individual. METHODS: We perform a comprehensive meta-analysis on 5596
      full envelope HIV genes generated by single genome amplification-direct
      sequencing from 182 incident and 43 chronic cases. We devise a binary
      classification test based on the tail characteristics of the Hamming distance
      distribution of sequences. RESULTS: We identify a clear signature of incident
      infections, the presence of closely related strains in the sampled HIV envelope
      gene sequences in each HIV-infected patient, in both single-variant and
      multivariant transmissions. The sequence similarity used as a biomarker is found
      to have high specificity and sensitivity, greater than 95%, and is robust to
      viral and host-specific factors such as the clade of the viral strain, viral
      load, and the length and location of sequences in the HIV envelope gene.
      CONCLUSION: Because of rapid and continuing improvements in sequencing technology
      and cost, sequence-based incidence assays hold great promise as a means of
      quantifying HIV incidence from a single blood test.

PMID- 21716076
TI  - The cost-effectiveness of symptom-based testing and routine screening for acute
      HIV infection in men who have sex with men in the USA.
AB  - OBJECTIVE: Acute HIV infection often causes influenza-like illness (ILI) and is
      associated with high infectivity. We estimated the effectiveness and cost
      effectiveness of strategies to identify and treat acute HIV infection in men who
      have sex with men (MSM) in the USA. DESIGN: Dynamic model of HIV transmission and
      progression. INTERVENTIONS: We evaluated three testing approaches: viral load
      testing for individuals with ILI, expanded screening with antibody testing, and
      expanded screening with antibody and viral load testing. We included treatment
      with antiretroviral therapy for individuals identified as acutely infected. MAIN
      OUTCOME MEASURES: New HIV infections, discounted quality-adjusted life years
      (QALYs) and costs, and incremental cost-effectiveness ratios. RESULTS: At the
      present rate of HIV-antibody testing, we estimated that 538,000 new infections
      will occur among MSM over the next 20 years. Expanding antibody screening
      coverage to 90% of MSM annually reduces new infections by 2.8% and costs US$
      12,582 per QALY gained. Symptom-based viral load testing with ILI is more
      expensive than expanded antibody screening, but is more effective and costs US$
      22,786 per QALY gained. Combining expanded antibody screening with symptom-based
      viral load testing prevents twice as many infections compared to expanded
      antibody screening alone, and costs US$ 29,923 per QALY gained. Adding viral load
      testing to all annual HIV tests costs more than US$ 100,000 per QALY gained.
      CONCLUSION: Use of HIV viral load testing in MSM with ILI prevents more
      infections than does expanded annual antibody screening alone and is inexpensive
      relative to other screening interventions. Clinicians should consider symptom
      based viral load testing in MSM, in addition to encouraging annual antibody
      screening.

PMID- 21716077
TI  - Abacavir use and cardiovascular disease events:  a meta-analysis of published and
      unpublished data.
AB  - BACKGROUND: The use of abacavir (ABC) has been associated with an increased risk
      of cardiovascular disease in some cohort studies. However, no excess risk of
      myocardial infarction (MI) with ABC therapy has been observed in individual
      randomized clinical trials (RCTs) and in the aggregated clinical trials database
      maintained by the manufacturer of ABC. OBJECTIVE: To combine all the evidence
      from RCTs by means of meta-analysis to estimate the effect of combined
      antiretroviral therapy (cART) containing ABC on MI and overall major
      cardiovascular events (CVEs). METHODS: Primary outcomes included MI, CVE, adverse
      events requiring discontinuation of treatment, and overall mortality. We used a
      conventional Mantel-Haenszel method, with risk ratio and 95% confidence intervals
      (CIs) or, in the presence of heterogeneity, a random-effect model. RESULTS: Data
      were from 28 primary RCTs (9233 participants) comparing ABC-containing cART (4376
      participants) to other regimens not containing ABC (4857 controls). MI data were
      available from 18 trials (31 episodes in 7054 patients) and CVE data from 20
      trials (79 episodes in 7899 patients). Compared to the controls, ABC use did not
      increase significantly the occurrence of MI (risk ratio 0.73, 95% CI 0.39-1.35; P
      = 0.31), CVE (risk ratio 0.95, 95% CI 0.62-1.44; P = 0.80), overall mortality
      (risk ratio 1.20, 95% CI 0.63-2.27; P = 0.58), and adverse events requiring
      discontinuation of treatment (risk ratio 0.82, 95% CI 0.67-1.00; P = 0.05).
      CONCLUSION: This meta-analysis of RCTs does not support the hypothesis that ABC
      containing cART regimens carry a greater risk of MI or major cardiovascular
      events relative to comparator cART.

PMID- 21716078
TI  - Impact of lamivudine on HIV and hepatitis B virus-related outcomes in
      HIV/hepatitis B virus individuals in a randomized clinical trial of
      antiretroviral therapy in southern Africa.
AB  - OBJECTIVE: To examine HIV and hepatitis B virus (HBV)-related outcomes in HIV/HBV
      coinfected participants in the PHIDISA II study by use of HBV-active vs. non-HBV
      active antiretroviral therapy (ART). DESIGN AND METHODS: PHIDISA II was a
      randomized study of ART therapy in HIV-infected adults employing zidovudine along
      with didanosine, or lamivudine along with stavudine in a factorial 2x2 design.
      HIV/HBV-coinfected participants by randomization received HBV-active or non-HBV
      active ART. The following outcomes of interest were examined: immunological
      recovery and HIV RNA suppression; hepatic flare; HBV DNA suppression; and
      mortality. RESULTS: HIV/HBV coinfection was present in 106 of 1771 (6%) of
      participants. Participants with HIV/HBV coinfection were more likely to be men,
      and have higher baseline alanine aminotransferase, lower albumin, and lower
      platelets than those with HIV monoinfection. Median CD4 cell gain and HIV RNA
      suppression was similar across all groups. Hepatic flare was observed in 9.4% of
      coinfected and 0.02% monoinfected participants. HBV DNA suppression (<55 IU/ml)
      at week 48 was observed in only 33% of those on lamivudine vs. 13% in those on no
      HBV-active drugs (P = 0.13). Mortality over follow-up was significantly greater
      in coinfected (17%) than monoinfected (11%) participants (P = 0.04). CONCLUSION:
      In summary, the use of lamivudine-containing ART in HIV/HBV participants in
      PHIDISA II resulted in little additional benefit over that of ART itself and
      failed to impact on the greater mortality in this group. These data provide
      strong support for recent guidelines advocating the use of tenofovir in all HIV
      HBV-coinfected individuals initiating ART.

PMID- 21716079
TI  - Assessment of copy number status of chromosomes 6 and 11 by FISH provides
      independent prognostic information in primary melanoma.
AB  - Melanoma incidence has been rising steadily for decades, whereas mortality rates
      have remained flat. This type of discordant pattern between incidence and
      mortality has been linked to diagnostic drift in cancers of the thyroid, breast,
      and prostate. Ancillary tests, such as fluorescent in situ hybridization (FISH),
      are now being used to help differentiate melanomas from melanocytic nevi.
      Multicolor FISH has been shown to distinguish between these 2 with 86.7%
      sensitivity and 95.4% specificity. To assess the ability of FISH to differentiate
      melanomas with metastatic or lethal potential from those with an indolent disease
      course, we performed FISH with probes targeting 6p25, centromere 6, 6q23, and
      11q13 on 144 primary melanomas with a minimal tumor thickness of 2 mm and
      compared the development of metastatic disease and melanoma-specific mortality as
      well as relapse-free and disease-specific survival between FISH-positive and FISH
      negative cases. Of the melanomas, 82% were positive by FISH according to
      previously defined criteria. The percentage was significantly higher (93%) in
      cases that developed systemic metastases (n=43) than in patients that did not
      (77%, n=101). FISH-positive primaries had a significantly increased risk of
      metastasis or melanoma-related death compared with FISH-negative cases odds ratio
      4.11; confidence interval, 1.14-22.7 and odds ratio 7.0, confidence interval 1.03
      300.4, respectively. FISH status remained an independent parameter when
      controlling for known prognostic factors. These data indicate that the group of
      melanomas diagnosed with routine histopathology that lack aberrations detected by
      FISH is enriched for melanomas with a more indolent disease course. This suggests
      that molecular techniques can assist in a more accurate identification of tumors
      with metastatic potential.

PMID- 21716080
TI  - Hyalinizing cholecystitis and associated carcinomas: clinicopathologic analysis
      of a distinctive variant of cholecystitis with porcelain-like features and
      accompanying diagnostically challenging carcinomas.
AB  - We describe a clinicopathologically distinct subtype of cholecystitis, the
      extensively calcific version of which has been presented in the clinical
      literature as "porcelain gallbladder (PG)." This cholecystitis, which we propose
      to refer to as hyalinizing cholecystitis (HC), is characterized by dense,
      paucicellular hyaline fibrosis transforming the gallbladder (GB) wall into a
      relatively thin and uniform band. The process diffusely effaces most of the
      normal structures of GB, and some cases show calcifications. To determine the
      clinicopathologic associations of HC, we systematically analyzed 4231
      cholecystectomies (606 of which had carcinoma) histopathologically, in addition
      to a targeted search in our databases. Ninety-six cases of HC were identified
      (1.6% of cholecystectomies). Patients with HC were a decade older than ordinary
      cholecystitis patients (56 vs. 47; P<0.001), suggesting that HC may be a long
      term complication of chronic injury in some patients. Calcifications of variable
      amounts and degrees were identified in two thirds of the cases. In addition, 10
      cases showed diffuse marked calcifications and were considered separately as
      "complete porcelain" GB. Thirty-eight HC cases had carcinoma with a calculated
      frequency of 15% and an odds ratio of cancer risk of 4.6. Only 42% of the
      invasive cases were associated with calcifications; none of the 10 diffusely
      calcific cases had carcinoma. HC-related carcinomas were challenging
      diagnostically. They did not form distinct masses or any significant thickening
      (mean thickness, 2.6 vs. 4.0 mm in ordinary adenocarcinomas; P<0.002).
      Microscopically, they had widely scattered and bland-appearing glands embedded in
      the thin band of hyaline stroma of HC, commonly showing a disappearing lining,
      leaving behind the granular, necrotic intraluminal debris (regression) with or
      without calcifications, which could be the only sign of cancer in some sections.
      The morphologic features that allowed the recognition of these glands as
      malignant included their longitudinal axis parallel to the surface, their
      irregular contours, clear cytoplasm with distinct borders, nuclear
      irregularities, and washed-off chromatin. Surface epithelium, if preserved (and
      it was not in most cases), typically showed carcinoma in situ of either denuding
      or micropapillary types. HC-associated carcinomas, with a median survival of 7
      months, appeared to have a clinical course at least as aggressive as that of
      regular carcinomas (median survival 12 months; P=0.02). In conclusion, HC is a
      distinct clinicopathologic entity, which is often associated with carcinoma, and
      the carcinomas arising from this group are often very subtle and prone to
      misdiagnosis microscopically. As HC is typically devoid of epithelium, any
      glandular elements on the wall of HC should be regarded as a suspect for
      carcinoma. This study also confirms recent findings in the radiology literature
      it is not the complete (diffusely calcific) PG that is associated with cancer.
      Instead, a distinct, histopathologically defined form of cholecystitis, HC with
      minimal or no calcifications (incomplete PG), is associated with invasive
      carcinoma. Thus, imaging protocols ought to focus on the correlates of HC rather
      than fixating on calcifications. Further studies into the pathogenesis of this
      process and its mechanisms of progression to carcinoma are warranted.

PMID- 21716081
TI  - Pulmonary tumor with notochordal differentiation: report of 2 cases suggestive of
      benign notochordal cell tumor of extraosseous origin.
AB  - Intraosseous benign notochordal cell tumor (BNCT) is a lesion postulated to be of
      notochordal cell origin. BNCT has recently been recognized as a potential
      precursor of classic chordoma, a rare malignant neoplasm usually presenting in
      the sacrococcygeal region, skull base, or mobile spine. Extra-axial chordoma is
      extremely rare, and only 2 cases of pulmonary chordoma have been reported
      previously. We describe herein 2 cases of hitherto-unreported lung tumors that
      were diagnosed as BNCT. The patients were a middle-aged asymptomatic man and
      woman who were each incidentally found to have a 15-mm pulmonary nodule on
      computed tomography. They underwent surgical resection of the tumors under a
      diagnosis of probable benign tumor of uncertain nature. Histopathologically, both
      tumors showed solid sheets of peculiar adipocyte-like univacuolated cells,
      multivacuolated cells, and less vacuolated cells with small, round nuclei and
      mildly eosinophilic cytoplasm. Mitosis was absent. These features were typical of
      BNCT. Immunohistochemically, the tumor cells in both cases were positive for
      brachyury, a transcription factor essential for notochordal cell differentiation
      and for other markers of notochordal cells including cytokeratins, vimentin, and
      S-100 protein. Postoperatively, extensive radiographic examination of the whole
      body revealed no evidence of a primary tumor elsewhere, and both patients are
      alive and well, with no evidence of disease 1 year after surgery. These 2 cases
      raise the possibility of a new explanation for the histogenesis of extra-axial
      chordomas: BNCT may be a precursor lesion of not only conventional axial chordoma
      but also of extra-axial chordoma.

PMID- 21716082
TI  - Collagenous ileitis: a study of 13 cases.
AB  - Collagenous ileitis (CI), characterized by subepithelial collagen deposition in
      the terminal ileum, is an uncommon condition. The few cases reported to date have
      been associated with collagenous colitis (CC) or lymphocytic colitis. Thirteen
      cases of CI retrieved over a 9-year period were retrospectively studied. There
      were 7 female and 6 male patients, with an age range of 39 to 72 years (mean, 64
      y). Two groups were identified: (1) CI associated with collagenous or lymphocytic
      disease elsewhere in the gastrointestinal tract and (2) CI as an isolated
      process. Diarrhea was the presenting symptom in 11 cases. Most patients had no
      regular medication use. Subepithelial collagen thickness ranged from 15 to 100
      MUm (mean, 32 MUm) and involved 5% to 80% of the subepithelial region of the
      submitted biopsies. Six cases had >25 intraepithelial lymphocytes (IELs)/100
      epithelial cells, and villous blunting was observed in 11 cases. Chronic
      inflammation of the lamina propria was present in 9 cases, and focal neutrophil
      infiltration was identified in 3 cases. In biopsies taken from other sites, 7 of
      13 colonic biopsies showed CC, 4 of 9 gastric biopsies showed collagenous
      gastritis, and 2 of 10 duodenal biopsies were abnormal with collagenous sprue
      (n=1) and partial villous atrophy and increased IELs (n=1) (both celiac disease
      related). Resolution of the subepithelial collagen deposition was found in the 1
      case in which follow-up of terminal ileal biopsies were taken. There was partial
      or complete resolution of symptoms in 6 of 9 patients for whom follow-up
      information was available.

PMID- 21716083
TI  - Initial high-grade prostatic intraepithelial neoplasia with carcinoma on
      subsequent prostate needle biopsy: findings at radical prostatectomy.
AB  - There are only a few small studies on men with an initial biopsy showing high
      grade prostatic intraepithelial neoplasia (HGPIN) who later have cancer on repeat
      biopsy and then undergo radical prostatectomy. It is unknown whether this
      scenario impacts the prognosis of subsequent radical prostatectomy. We compared
      radical prostatectomy findings in 45 men with an initial diagnosis of HGPIN who
      subsequently were diagnosed with cancer with 18,494 men diagnosed with cancer who
      lacked an earlier diagnosis of HGPIN. All cases were retrieved from our
      institution between 1993 and 2008. The mean patient age was 60.2 years, and the
      mean serum prostate-specific antigen value was 9.0 ng/mL. For the 45 men with an
      initial HGPIN diagnosis, 21 of 45 (46.7%) men were found to have cancer within 6
      months and 29 of 45 (64.4%) within 1 year after the diagnosis of HGPIN. Cancer
      involved a single core in 32 of 45 (71.1%) cases, and the maximum tumor volume
      was <=5% in 57.8% of the 45 cases. Men with initial HGPIN had 84.4% organ
      confined cancer, whereas cases without HGPIN had 65.4% organ-confined cancer
      (P=0.007) at radical prostatectomy. For the RPs performed in men with an earlier
      diagnosis of HGPIN followed by cancer on biopsy, the mean and median tumor
      volumes were 0.3 cm3 and 0.12 cm3 (0.003 cm3 to 1.46 cm3). Favorable pathologic
      stage was maintained even when we restricted the analysis to men with only
      Gleason score 6 cancer on biopsy. In men with Gleason score 6 cancer on biopsy,
      men with an initial diagnosis of HGPIN had 88.9% organ confined versus 73.2% for
      men with no earlier biopsy diagnosis of HGPIN, (P=0.03). At radical
      prostatectomy, although men with an earlier HGPIN diagnosis had less adverse
      findings in terms of Gleason score, surgical margin involvement, seminal vesicle
      involvement, and lymph node metastasis, the differences did not reach statistical
      significance. This was possibly due to the relatively small number of positive
      events in the men with no earlier HGPIN and due to the relatively small number of
      cases with earlier HGPIN. Prostatic adenocarcinomas discovered after an initial
      HGPIN diagnosis on biopsy are more likely to be organ confined, yet of similar
      grade, compared with cases diagnosed as cancer on the first biopsy. These
      findings likely reflect cancers associated with HGPIN, in which the cancers were
      missed on the initial biopsy as a result of smaller size.

PMID- 21716084
TI  - Palisade vessels as a new histologic marker of esophageal origin in ER specimens
      from columnar-lined esophagus.
AB  - It is difficult for surgical pathologists to determine the origin of tissues in
      samples taken from the columnar-lined esophagus (CLE) or stomach by biopsy or
      endoscopic resection (ER) on the basis of histologic examination alone. We
      examined histopathologically a single section (5 to 22 mm in size; mean, 12 mm)
      from each of 66 cases of CLE (36 short segments, 30 long segments) from German
      patients with reference to 3 histologic markers of esophageal origin: esophageal
      glands proper and/or ducts, squamous islands, and double muscularis mucosae, all
      of which had been reported previously, and palisade vessels as a new histologic
      parameter as well. Palisade vessels were defined histologically as veins >100 MUm
      in size in and above the original muscularis mucosae. Esophageal glands proper
      and/or ducts, squamous islands, and double muscularis mucosae were seen in 33%,
      18%, and 71% of the specimens, respectively. Palisade longitudinal vessels were
      observed in 78% and 63% of specimens of short-segment and long-segment CLE,
      respectively. Palisade vessels were never seen in ER specimens from the stomach
      or in the middle esophagus and stomach among control autopsy specimens. At least
      1 of these 4 markers was seen in 88% of the sections. Therefore, ER specimens
      were confirmed to originate from CLE in 88% of single histologic sections of CLE
      on the basis of histologic examination alone.

PMID- 21716085
TI  - Grading of clear cell renal cell carcinoma should be based on nucleolar
      prominence.
AB  - Fuhrman grading of renal cell carcinoma focuses on features of nuclear size,
      nuclear shape, and nucleolar prominence. Despite the reported widespread usage of
      Fuhrman grading in clinical studies, there is debate as to the prognostic
      significance and reproducibility of its criteria. It has been noted that many
      pathologists rely on assessment of nucleolar prominence alone when grading renal
      cell carcinoma; however, the validity of this remains unconfirmed. This study was
      undertaken to determine the relationship of the 3 morphologic components of the
      Fuhrman grading system with one another and to determine which, if any of these,
      can be correlated with outcome for clear cell renal cell carcinoma. One hundred
      twenty-one organ-confined clear cell renal cell carcinomas were examined in this
      study. Parameters of nuclear size (area, major axis, perimeter) and nuclear shape
      (shape factor, nuclear compactness) were assessed by image analysis, whereas
      nucleolar prominence was assigned (grades 1 to 3) using the criteria of Fuhrman.
      On the basis of the predominant grade present, there were 17 nucleolar grade 1,
      90 nucleolar grade 2, and 14 nucleolar grade 3 tumors. When the high-power field
      in each tumor with the worst nucleolar grade was assessed, there was 1 nucleolar
      grade 1, 68 nucleolar grade 2, and 52 nucleolar grade 3 tumors. Predominant and
      worst nucleolar grade correlated with all measures of nuclear size, but not
      nuclear shape. Worst nucleolar grade and all parameters of nuclear size were
      significantly associated with outcome. On multivariate analysis, worst nucleolar
      grade retained a significant association with survival when modeled with nuclear
      area. Neither worst nucleolar grade nor major nuclear axis/nuclear perimeter was
      significantly associated with survival when modeled together. In this study, we
      have shown that worst nucleolar grade and nuclear size are of prognostic
      significance for clear cell renal cell carcinoma. We have further shown the
      association of worst nucleolar grade with outcome to be independent of nuclear
      area, whereas it is a dependent variable when tested against other parameters of
      nuclear size. These findings indicate that worst nucleolar grading alone is a
      valid grading parameter for clear cell renal cell carcinoma.

PMID- 21716086
TI  - Clinicopathologic and molecular features of 122 Brazilian cases of nodal and
      extranodal NK/T-cell lymphoma, nasal type, with EBV subtyping analysis.
AB  - Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent
      in Asia and in some areas of South and Central America, but it is rarely seen in
      the United States and Europe. In this study, a series of 122 cases of NK/TCL from
      Brazil was analyzed with respect to clinicopathologic features. Clinical
      characteristics and geographic distribution were evaluated in 97 cases of
      nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal
      cases. Clinical staging and follow-up information was available in a subset of 21
      patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed
      cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least
      1 marker for cytotoxic granules. The global distribution of EBV subtypes showed
      predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections
      were detected. TCR-gamma TCR-gene rearrangement was observed in 7 cases; all of
      them extranodal. Three of TCR-gamma(+) cases showed EBV subtype A. Two TCR
      gamma(+)/CD56(+) cases showed EBV subtype B. Geographic distribution of NK/TCL
      showed higher frequency in the southeast and northeast regions of Brazil.
      Striking differences among geographic regions were seen with the vast majority of
      EBV subtype B (86%) occurring in the south and southeast regions.

PMID- 21716087
TI  - Cribriform adenocarcinoma of minor salivary gland origin principally affecting
      the tongue: characterization of new entity.
AB  - We present a series of 23 cases of a distinctive, hitherto poorly recognized low
      grade adenocarcinoma, with several histologic features reminiscent of papillary
      carcinoma of the thyroid, and which mostly but not exclusively occurs in the
      tongue. All the tumors were unencapsulated and were divided into lobules that
      were composed mainly of cribriform and solid growth patterns. Therefore, we
      propose the name "cribriform adenocarcinoma of minor salivary gland origin
      (CAMSG)." All the patients were adults with a mean age at diagnosis of 55.8 years
      (range, 25 to 85 y). Fourteen of the 23 tumors were localized in the tongue, 3 in
      the soft palate, 2 in the retromolar buccal mucosa, 3 in the lingual tonsils, and
      1 in the upper lip. Fifteen patients of 23 had synchronous metastases in the
      cervical lymph nodes at the time of diagnosis, bilateral in 3 cases. In 3
      patients, the nodal metastasis was the first evidence of disease, later
      investigation revealing primary neoplasms in the base of tongue and tonsil,
      respectively. In addition, 1 patient developed a cervical lymph node metastasis 8
      years after excision of a primary tumor of the tongue. Data on treatment and
      follow-up were available in 14 cases. The patients were treated by radical
      excision with clear margins (12 cases) or by simple excision (2 cases). Neck
      dissection was performed in 10 patients; 9 received radiotherapy, but none were
      treated by chemotherapy. Clinical follow-up ranged from 2 months to 13 years
      (mean, 6 y and 5 mo). Twelve patients are alive with no evidence of recurrent or
      metastatic disease after treatment, 1 patient died 2 years after surgery without
      evidence of tumor, and 1 patient is alive with recurrent tumor of the palate.

PMID- 21716088
TI  - Malignant fat-forming solitary fibrous tumor (so-called "lipomatous
      hemangiopericytoma"): clinicopathologic analysis of 14 cases.
AB  - Fat-forming solitary fibrous tumor is a rare variant of solitary fibrous tumor
      (SFT). Generally regarded as benign, very few fat-forming SFTs with malignant
      histologic features have been reported. Here, we report 14 histologically
      malignant fat-forming SFTs to better characterize this subset. Seven patients
      were female and 7 were male, with ages ranging 20 to 93 years (median, 57 y).
      Five tumors were located in the lower limb, 3 in the trunk, 3 in abdominopelvic
      locations, 2 in the head and neck region, and 1 in the upper limb. The tumor size
      ranged from 3.4 to 20 cm (median, 8.6 cm). Histologically, all exhibited at least
      focal hypercellularity; 12 tumors had mitoses >4/10 high-power fields (range, 2
      to 37; median, 8), 12 showed at least moderate atypia, and 8 showed necrosis. It
      should be noted that 7 tumors contained only mature adipose tissue, whereas 5
      contained multivacuolated lipoblasts and 2 had areas resembling atypical
      lipomatous tumor (ALT). Immunohistochemically, CD34 and CD99 were positive in
      most cases (11 of 14 and 8 of 10, respectively); MDM2 and CDK4 were both negative
      in all 4 cases tested (including both tumors with ALT-like areas). Follow-up data
      from 10 cases (median duration, 47.5 mo; range, 5 to 76) showed 2 patients with
      multiple metastases (both to lung and bones, and 1 each to breast and to soft
      tissue), both of whom died of disease. In conclusion, fat-forming SFTs exhibiting
      malignant histologic features have potential for aggressive behavior. The
      presence of lipoblasts and/or ALT-like areas, although described in some "benign"
      examples of fat-forming SFT, seems much more common in the malignant subset and
      may prompt a careful search for morphologic evidence of malignancy in any case of
      fat-forming SFT.

PMID- 21716089
TI  - The lip tells tales of kidney disease.

PMID- 21716090
TI  - Note of editorial concern.

PMID- 21716091
TI  - Comparison of the accuracy of noninvasive hemoglobin monitoring by
      spectrophotometry (SpHb) and HemoCue(r) with automated laboratory hemoglobin
      measurement.
AB  - BACKGROUND: The reference method for hemoglobin concentration measurement remains
      automated analysis in the laboratory. Although point-of-care devices such as the
      HemoCue(r) 201+ (HemoCue, Angelholm, Sweden) provide immediate hemoglobin values,
      a noninvasive, spectrophotometry-based technology (Radical-7(r); Masimo Corp.,
      Irvine, CA) that provides continuous online hemoglobin (SpHb) measurements has
      been introduced. This clinical study aimed to test the hypothesis that SpHb
      monitoring was equivalent to that of HemoCue(r) (the automated hemoglobin
      measurement in the laboratory taken as a reference method) during acute surgical
      hemorrhage. METHODS: Blood for laboratory analysis was sampled after induction of
      anesthesia, during surgery according to the requirements of the anesthesiologist,
      and finally after the transfer of the patient to the recovery room. When each
      blood sample was taken, capillary samples were obtained for analysis with
      HemoCue(r). SpHb monitoring was performed continuously during surgery. Using the
      automated hemoglobin measurement in the laboratory as a reference method, the
      authors tested the hypothesis that SpHb monitoring is equivalent to that of
      HemoCue(r). The agreement between two methods was evaluated by linear regression
      and Bland and Altman analysis. RESULTS: Eighty-five simultaneous measurements
      from SpHb, HemoCue(r), and the laboratory were obtained from 44 patients. Bland
      and Altman comparison of SpHb and HemoCue(r) with the laboratory measurement
      showed, respectively, bias of -0.02 +/- 1.39 g . dl(-1) and -0.17 +/- 1.05 g .
      dl(-1), and a precision of 1.11 +/- 0.83 g . dl(-1) and 0.67 +/- 0.83 g . dl(-1).
      Considering an acceptable difference of +/- 1.0 g . dl(-1) with the laboratory
      measurement, the percentage of outliers was significantly higher for SpHb than
      for HemoCue(r) (46% vs. 16%, P < 0.05). CONCLUSIONS: Taking automated laboratory
      hemoglobin measurement as a reference, the study shows that SpHb monitoring with
      Radical-7(r) gives lower readings than does the HemoCue(r) for assessment of
      hemoglobin concentration during hemorrhagic surgery.

PMID- 21716092
TI  - Activation of opioid MU-receptors in the commissural subdivision of the nucleus
      tractus solitarius abolishes the ventilatory response to hypoxia in anesthetized
      rats.
AB  - BACKGROUND: : The commissural subnucleus of the nucleus tractus solitarius
      (comNTS) is a key region in the brainstem responsible for the hypoxic ventilatory
      response (HVR) because it contains the input terminals of the carotid
      chemoreceptor. Because opioids inhibit the HVR via activating central MU
      receptors that are expressed abundantly in the comNTS, the authors of the current
      study asked whether activating local MU-receptors attenuated the carotid body
      mediated HVR. METHODS: : To primarily stimulate the carotid body, brief hypoxia
      (100% N2) and hypercapnia (15% CO2) for 10 s and/or intracarotid injection of
      NaCN (10 MUg/100 MUl) were performed in anesthetized and spontaneously breathing
      rats. These stimulations were repeated after: (1) microinjecting three doses of
      MU-receptor agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) (approximately
      3.5 nl) into the comNTS; (2) carotid body denervation; and (3) systemic
      administration of DAMGO (300 MUg/kg) without and with previous intracomNTS
      injection of d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2, a MU-receptor antagonist.
      RESULTS: : Study results showed that DAMGO at 0.25 and 2.5, but not 0.025 mM,
      caused a similar decrease in baseline ventilation (approximately 12%). DAMGO at
      0.25 mM largely reduced (64%) the HVR, whereas DAMGO at 2.5 mM abolished the HVR
      (and the VE response to NaCN) and moderately attenuated (31%) the hypercapnic
      ventilatory response. Interestingly, similar HVR abolition and depression of the
      hypercapnic ventilatory response were observed after carotid body denervation.
      Blocking comNTS MU-receptors by d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2
      significantly attenuated the HVR depression by systemic DAMGO with little change
      in the DAMGO modulatory effects on baseline ventilation and the hypercapnic
      ventilatory response. CONCLUSION: : The data suggest that opioids within the
      comNTS, via acting on MU-receptors, are able to abolish the HVR by affecting the
      afferent pathway of the carotid chemoreceptor.

PMID- 21716093
TI  - Tricuspid valve repair in patients supported with left ventricular assist
      devices.
AB  - In patients with end-stage heart failure, severe tricuspid regurgitation (TR)
      might be one of the signs of biventricular failure with subsequent need for
      biventricular support (biventricular assist device [BVAD]) or total artificial
      heart (TAH). However, tricuspid valve repair (TVR) may avoid BVAD or TAH
      implantation. Consecutive patients with TR of grade 3+ receiving either left
      ventricular assist device with concomitant TVR (group A, n = 7) or a BVAD/TAH
      (group B, n = 18) implanted in our institution between 2007 and 2010 were
      compared retrospectively. Intermacs (Interagency Registry for Mechanically
      Assisted Circulatory Support) stage I, age less than 18 years, and postcardiotomy
      failure were the exclusion criteria. Preoperative parameters were similar in both
      groups. No differences in 30-day mortality (28.5% vs. 22.2%, p = 0.8),
      postoperative dialysis, intensive care unit (ICU) stay (35 vs. 22 days, p =
      0.94), or ventilation time (15 vs. 13 days) were seen. Timing of discharge home
      was similar in both groups (42.8% after a median of 45 days vs. 50% after a
      median of 40 days [p = 0.78]). Six months after surgery, no significant TR was
      seen in group A. Right ventricular failure requiring mechanical support occurred
      in 14.2% (n = 1) in group A. In patients with TR of grade 3+, left ventricular
      assist device support combined with TVR showed comparable results with
      biventricular support with regard to short-term outcome. These results led to a
      change of our established ventricular assist device implantation strategy.

PMID- 21716094
TI  - Drug-induced state-dependent learning: review of an operant procedure in rats.
AB  - Drug discrimination and drug state dependence are often thought to be based on
      the same drug actions, and to differ only in the doses needed to produce them,
      with discrimination occurring at low doses and state dependence at high doses.
      Testing this hypothesis has been hampered by the use of discrimination and state
      dependence procedures that differed in many respects. In 1986, Colpaert
      introduced a procedure to study state dependence in rats that used the same
      response, the same reinforcer, and the same reinforcement schedule that are
      commonly used in drug discrimination. Using this procedure, differences between
      drug state dependence and drug discrimination were found with some drugs (e.g.
      alcohol), consistent with the hypothesis that the procedures differ in the drug
      properties they measure, but not with other drugs (e.g. chlordiazepoxide). Thus,
      state dependence and drug discrimination can generate different outcomes, but the
      conditions in which they do require further study. However, all the studies
      conducted with the procedure introduced by Colpaert clearly show that state
      dependence is not necessarily only a high-dose phenomenon, but can also occur at
      doses at which many central nervous system drugs produce their characteristic
      effects. This finding led to the hypothesis that state dependence may be involved
      in the therapeutic and other effects of psychoactive drugs.

PMID- 21716095
TI  - THC-methadone and THC-naltrexone interactions on discrimination, antinociception,
      and locomotion in rats.
AB  - This study examined cannabinoid-opioid interactions within the same subjects on
      measures of discrimination, antinociception, horizontal locomotion, and
      catalepsy. Male Sprague-Dawley rats were trained to discriminate Delta(9)
      tetrahydrocannabinol (THC, 3 mg/kg) from vehicle. THC alone (0.32-10 mg/kg) dose
      dependently increased THC-appropriate lever responding and decreased response
      rate. THC alone also produced paw pressure antinociception and decreased
      locomotor activity, but did not produce catalepsy. Methadone (0.32-5.6 mg/kg) and
      naltrexone (0.32-3.2 mg/kg) alone produced low THC-appropriate lever responding
      up to doses that decreased response rate. When combined with THC, methadone (1.0
      mg/kg) flattened the THC discrimination curve, but did not affect antinociceptive
      or motoric effects of THC. Naltrexone did not alter any effects of THC. In rats
      that were not trained to discriminate THC from vehicle, 1.0 mg/kg methadone did
      enhance THC antinociception. These results suggest that MU-opioid receptor
      agonists can disrupt the discriminative stimulus effects of cannabinoids while
      not significantly altering their antinociceptive or motoric effects, in
      chronically drug-exposed subjects. Further research is required to determine
      whether opioid enhancement of cannabinoid antinociception is limited to acute
      exposure, or simply requires higher doses in chronically drug-exposed subjects.

PMID- 21716096
TI  - Hypoplasia/aplasia of pelvis, femora, fibulae, ulna, digits and nails: Fuhrmann
      syndrome without WNT7A mutations.

PMID- 21716097
TI  - Comparison of dynamic contour tonometry and Goldmann applanation tonometry in
      keratoconus.
AB  - PURPOSE: We performed a comparative study using Goldmann applanation tonometry
      (GAT) and dynamic contour tonometry (DCT) to measure intraocular pressure (IOP)
      in eyes with keratoconus. METHODS: IOP was measured in 114 eyes of 75 patients
      with keratoconus (51 men and 24 women; mean age, 36.1 +/- 11.2 years) using GAT
      and DCT in randomized order. Central corneal thickness (CCT), minimal corneal
      thickness (MCT), and corneal topography were recorded using the Pentacam. Four
      groups according to Amsler's keratoconus classification were composed and
      analyzed for significant differences of CCT, MCT, GAT, and DCT results. RESULTS:
      Mean CCT in the 114 keratoconus eyes was 481.1 +/- 46.2 MUm (range, 334-601 MUm).
      Mean MCT was 453.3 +/- 56.3 MUm (range, 239-573 MUm). Mean IOP measured using GAT
      was 13.1 +/- 2.9 mm Hg, whereas mean IOP measured using DCT was 14.8 +/- 2.6 mm
      Hg. Neither the results for GAT nor those for DCT showed a significant
      correlation with CCT (Pearson correlation: P < 0.05). Multifactorial analysis
      revealed that CCT and MCT, but not GAT and DCT, results were significantly
      different in corneas of varying curvatures. CONCLUSIONS: This study shows that
      DCT measures IOP higher than GAT in eyes with keratoconus. In keratoconus, both
      methods seem to be independent of CCT and therefore are equally, but not
      interchangeably, applicable when monitoring IOP. Further analysis revealed that
      CCT and MCT are significantly different in corneas of varying Amsler grade.

PMID- 21716098
TI  - A histopathological study of bulbar conjunctival flaps occurring in 2 contact
      lens wearers.
AB  - PURPOSE: To study the histopathology of paralimbal bulbar conjunctival flaps
      occurring secondary to soft contact lens wear. METHODS: Slit-lamp biomicroscopy
      using sodium fluorescein, cobalt blue light, and a Wratten filter was used to
      observe the presence, location, and dimensions of bulbar conjunctival flaps
      presenting in a cohort of contact lens wearers. Two subjects who exhibited such
      flaps agreed to undergo conjunctival biopsy. Tissue samples, obtained from the
      region of the flap, and an adjacent unaffected area were processed by standard
      histopathological methods. RESULTS: In the first subject, analysis of the flap
      tissue showed even collagen distribution and overall normal histology. The flap
      of the second subject displayed a mild focal increase in collagen and mild
      degeneration of collagen, but no increase in elastic tissue. Conjunctival
      epithelium was normal in both cases. CONCLUSIONS: In these 2 subjects,
      conjunctival flap tissue either was normal or showed only minimal abnormality.
      There is insufficient evidence for significant pathological change on the time
      scale of this study.

PMID- 21716099
TI  - Precise temperature control of donor cornea tissue with reusable passive thermal
      container.
AB  - PURPOSE: To describe a new reusable passive thermal shipping container for
      domestic and international transport of human donor cornea, which maintains air
      temperature for 72 consecutive hours of harsh hypothermic and hyperthermic
      environmental challenges. METHODS: The passive thermal container (PTC) was
      prepared by storing the device at -30 degrees C for 8 hours. On full activation
      of the biphasic wax-based compound, 2 human corneas for research and future
      histological studies were secured in either of 2 similarly prepared PTCs or 2
      polystyrene containers with wet ice. Three thermal data loggers were enclosed in
      the bottom, side, and middle of each payload area. The container was then exposed
      to hyperthermic (range, 21.1 to 51.7 degrees C) or hypothermic (range, 15.6 to 
      28.9 degrees C) external temperatures for 72 hours after which all corneas were
      removed, and the air temperature readings from the loggers were reviewed.
      RESULTS: Air temperature stability was measured at 5-minute intervals. The PTC
      maintained steady acceptable air temperatures for 71.13 consecutive hours in the
      hyperthermic challenge and 60.33 consecutive hours in the hypothermic challenge.
      The polystyrene containers with wet ice did not maintain a payload temperature
      between 2 and 8 degrees C for more than 8 consecutive hours during the
      hypothermic challenge and never achieved industry regulation temperatures during
      the hyperthermic challenge. CONCLUSIONS: We present a novel method for
      transporting human corneal tissue that ensures proper air temperature stability
      between 60 and 71 hours in harsh hypothermic and hyperthermic environments, which
      is also reusable. There may be applications for this technology in both domestic
      and international transportation of corneal tissue.

PMID- 21716100
TI  - Modified deep anterior lamellar keratoplasty in the management of small and large
      epithelialized descemetoceles.
AB  - PURPOSE: Descemetocele is a severe complication of corneal ulceration associated
      with a high risk of perforation. We describe a modified air-assisted deep
      anterior lamellar keratoplasty (DALK) technique for the surgical management of
      small and large epithelialized descemetoceles. METHODS: Two representative cases
      are presented, one with a small (2 mm) and one with a large (4 mm) descemetocele.
      In both cases, the air-assisted lamellar dissection allowed a superficial
      keratectomy and access to the Descemet membrane. Viscoelastic was then directly
      injected through the stromal hole to separate the Descemet membrane from the
      posterior stroma, thereby allowing its complete removal. RESULTS: DALK was
      successfully performed using this modified air-assisted DALK technique. Visual
      acuity improved from counting fingers and hand motion to 20/40 and was maintained
      for at least 1 year after surgery. CONCLUSIONS: These cases demonstrate that the
      modified air-assisted DALK technique may be proposed for the management of small
      and large descemetoceles, allowing both tectonic and visual rehabilitation.

PMID- 21716101
TI  - Donor cornea tissue with prior radial keratotomy: is it suitable for descemet
      stripping automated endothelial keratoplasty?

PMID- 21716103
TI  - Refractive and keratometric outcomes of intacs continue to improve until 6
      months.

PMID- 21716104
TI  - Indications for single-dose activated charcoal administration in acute overdose.
AB  - PURPOSE OF REVIEW: Gastrointestinal decontamination in overdose patients remains
      a controversial problem in emergency medicine. There has been a significant
      decrease in the use of single-dose activated charcoal (SDAC) in recent years
      based on little new evidence and possibly because the overall mortality in
      overdose patients is low. RECENT FINDINGS: Human volunteer studies suggest SDAC
      is effective and this effect occurs for up to 4 h after ingestion, but the
      magnitude of the reduction in area under the curve (AUC) decreases over time. Two
      randomized controlled trials including one recent large study did not find SDAC
      to be beneficial. Pharmacokinetic and pharmacodynamic studies of specific drugs
      in overdose suggest that for most drugs SDAC decreases drug exposure, but this
      does not translate to clinical benefit in all cases. The administration of SDAC
      is a low-risk intervention. SUMMARY: Although SDAC is unlikely to be beneficial
      in many overdose patients, for some subgroups with severe poisoning, the benefits
      will outweigh the low risk of administration. The use of SDAC should be based on
      the potential toxicity of the drug ingested and the potential benefit of SDAC
      balanced against the willingness of the patient to take SDAC and the low risk of
      administration.

PMID- 21716105
TI  - Acute pain management of patients with multiple fractured ribs: a focus on
      regional techniques.
AB  - PURPOSE OF REVIEW: Thoracic trauma leading to multiple fractured ribs (MFR)
      remains very common. Good analgesia may help to improve a patient's respiratory
      mechanics and to avoid intubation of the trachea for ventilatory support and
      therefore may dramatically alter the course of recovery. We herein review the
      analgesia options for patients with MFR. RECENT FINDINGS: For healthy patients
      with one to two fractured ribs, systemic analgesics may suffice. For more than
      three to four fractured ribs, studies and experience have reaffirmed the superior
      analgesia made possible with thoracic epidural, thoracic paravertebral, and
      intercostal blocks. From experience, interpleural block has significant
      drawbacks. Catheterization allows the continuation of analgesia for 2 or more
      days with just one block. Use of the landmark technique is usually satisfactory
      for accurate block placement but ultrasound and nerve stimulation are showing
      promise in further improving needle and catheter placement accuracy, especially
      in the presence of difficult anatomy. SUMMARY: Thoracic epidural, thoracic
      paravertebral, and intercostal blocks are the top choices for patients with MFR
      and they are of equivalent efficacy. Each has unique advantages and
      disadvantages. Our preference tends to be the thoracic paravertebral approach.

PMID- 21716106
TI  - Management of severe acute asthma in the emergency department.
AB  - PURPOSE OF REVIEW: Asthma is one of the most common chronic diseases in most
      developed countries and control may be elusive. Deterioration in asthma control
      is common when patients are exposed to airway irritants, viruses, and/or when
      adherence to chronic anti-inflammatory medications is suboptimal. Acute asthma
      exacerbations are common, important reasons for presentations to emergency
      departments, and severe cases may result in hospitalization. Important knowledge
      gaps exist in what is known and what care is delivered at the bedside. RECENT
      FINDINGS: The literature in asthma is rapidly expanding and recent advances in
      the care are important to summarize. Systematic reviews, especially high-quality
      syntheses performed using Cochrane methods, provide the best evidence for busy
      clinicians to remain current. Management of asthma is based on early recognition
      of severe disease with aggressive therapy using multimodal interventions that
      focus on both bronchoconstriction and inflammatory mechanisms. SUMMARY: Treatment
      of severe acute asthma can effectively and safely reduce hospitalizations, airway
      interventions, and even death. Using the approach outlined herein will enable
      clinicians to assist patients to rapidly regain asthma control, return to normal
      activities, and improve their quality of life in the follow-up period.

PMID- 21716107
TI  - Cardiac tamponade.
AB  - PURPOSE OF REVIEW: To re-emphasize the epidemiology, pathophysiology, diagnosis,
      and treatment of cardiac tamponade. RECENT FINDINGS: Cardiac tamponade is a cause
      of obstructive shock. Incidence of cardiac tamponade is poorly documented. In
      cardiac tamponade, the pericardial pressure may reach 15-20  mmHg, leading to an
      equalization of pressures into the cardiac chambers and to a huge decrease in the
      systemic venous return. The right atrial transmural pressure becomes negligible.
      A competition between the right atrium and the right ventricle and between both
      ventricles is occurring. Deep inspiration allows the patients to maintain the
      systemic venous return at a certain level. Echocardiography is the key tool to
      diagnose a pericardial effusion, to detect its bad-tolerance, and to guide the
      treatment. In some situations following cardiac surgery, transesophageal
      echocardiography is mandatory. Treatment aims to restore a 'normal' blood
      pressure by fluid loading (with caution) and catecholamines and to drain the
      pericardium in emergency. SUMMARY: Cardiac tamponade is responsible for an
      obstructive shock. Causes of pericardial effusion are numerous. Echocardiography
      is the fundamental tool for the diagnosis and therapeutic management. Volume
      resuscitation and catecholamines are temporary treatments, pericardial drainage
      remaining the only effective treatment.

PMID- 21716108
TI  - Increased blood troponin levels in ICU patients.
AB  - PURPOSE OF REVIEW: Cardiac troponins in serum have become the biomarkers of
      choice for the diagnosis of myocardial infarction. Yet, troponin can also be
      elevated by a multitude of causes in the absence of overt myocardial ischemia.
      Such nonspecific elevations are particularly common in the critically ill. This
      article aims to provide information on the significance of troponin elevations in
      unselected critically ill patients and in patients with sepsis or septic shock.
      RECENT FINDINGS: Recent studies reconsider the possible association of troponin
      elevations with myocardial infarction in unselected critically ill patients.
      There are also more data on the prognostic significance of troponin in this
      population. In patients with sepsis, recent studies suggest that troponin may be
      a reliable index of sepsis-induced myocardial dysfunction, although the
      implications of this finding in the management of sepsis remain unclear for the
      time being. Troponin also appears to be a predictor of short and possibly also
      long-term outcome in septic patients. The advent of newer assays with even higher
      sensitivity, may lead to further redefinition of the role of troponin in the ICU.
      SUMMARY: Troponin is frequently elevated in critically ill patients. More
      research is needed on the diagnostic and prognostic significance and possible
      clinical applications of troponin measurements in patients with sepsis and
      critical illness.

PMID- 21716109
TI  - Sudden cardiac death in young athletes and nonathletes.
AB  - PURPOSE OF REVIEW: This article will review the incidence and most common causes
      of sudden cardiac death (SCD) in healthy young adults, including competitive
      athletes, as well as members of the general population. RECENT FINDINGS: SCD is
      rare but devastating in a young individual. The incidence of SCD in the young
      ranges from as low as 0.4 per 100,000 patient-years to as high as 13.4 per
      100,000 patient-years. SCD occurs in all populations, not only in athletes.
      SUMMARY: Whether SCD is more common in athletes is the cause of continued debate
      stemming from conflicting data. Hypertrophic cardiomyopathy is the most common
      underlying cause of SCD in young athletes in most series; however, in nonathletic
      populations, the underlying causes of SCD are more varied.

PMID- 21716110
TI  - Renal dysfunction and fluid and electrolyte disturbances.
AB  - PURPOSE OF REVIEW: To examine recent developments in preventing and treating
      postoperative acute renal dysfunction. To review contemporary issues concerning
      perioperative fluid and electrolyte management. RECENT FINDINGS: Renal
      dysfunction remains a major postoperative morbidity despite the advent of
      intermittent and continuous renal replacement therapies. It is also associated
      with increased mortality. Newer techniques, such as off-pump coronary artery
      bypass surgery, which promised to reduce the incidence of postoperative renal
      injury, have failed to do so. In addition, newer techniques such as endovascular
      repair of aortic disorder and the transcutaneous insertion of aortic valves are
      associated with substantial degrees of kidney injury partially due to the use of
      much intravenous contrast material. Therefore, the present-day approach to
      preventing contrast-induced nephropathy is reviewed. Electrolyte disturbances are
      especially problematic after certain types of surgery, such as trans-sphenoidal
      adenomectomy and surgeries requiring the use of large volumes of irrigating
      solutions. SUMMARY: Renal dysfunction, along with fluid and electrolyte
      disturbances, is a major issue that needs to be considered as part of
      perioperative management. Moreover, it is the prevention of clinically
      significant renal injury and electrolyte disturbances that is the cornerstone of
      contemporary anesthetic and surgical care.

PMID- 21716111
TI  - Postoperative cognitive disorders.
AB  - PURPOSE OF REVIEW: The elderly are the fastest growing segment of the population
      and undergo 25-30% of all surgical procedures. Postoperative cognitive problems
      are common in older patients following major surgery. The socioeconomic
      implications of these cognitive disorders are profound; cognitive decline is
      associated with a loss of independence, a reduction in the quality of life, and
      death. This review will focus on the two most common cognitive problems following
      surgery: postoperative delirium and postoperative cognitive dysfunction (POCD).
      RECENT FINDINGS: For years, preoperative geriatric consultation/screening was the
      only intervention proven to decrease postoperative delirium. There are, however,
      several recent publications indicating that preoperative and postoperative
      pharmacological and medical (hydration, oxygenation) management can reduce
      postoperative delirium. Spinal anesthesia with minimal propofol sedation has been
      shown to decrease the incidence of postoperative delirium in hip-fracture
      patients. Likewise, dexmedetomidine sedation in mechanically ventilated patients
      in the ICU is associated with less postoperative delirium and shorter ventilator
      times. Preoperative levels of education and brain function (cognitive reserve)
      may predict patients at risk for postoperative cognitive problems. Reduced white
      matter integrity is reported to place patients at a higher risk for both
      postoperative delirium and POCD. SUMMARY: The etiology of postoperative cognitive
      problems is unknown, but there is emerging evidence that decreased preoperative
      cognitive function contributes to the development of postoperative delirium and
      POCD. There is growing concern that inhalation anesthetics may be neurotoxic to
      the aging brain, but there are no human data evaluating this hypothesis to date.
      Randomized controlled trials evaluating interventions to improve long-term
      cognitive outcomes in elderly patients are urgently needed.

PMID- 21716112
TI  - Listening comprehension across the adult lifespan.
AB  - OBJECTIVES: Although age-related declines in perceiving spoken language are well
      established, the primary focus of research has been on perception of phonemes,
      words, and sentences. In contrast, relatively few investigations have been
      directed at establishing the effects of age on the comprehension of extended
      spoken passages. Moreover, most previous work has used extreme-group designs in
      which the performance of a group of young adults is contrasted with that of a
      group of older adults and little if any information is available regarding
      changes in listening comprehension across the adult lifespan. Accordingly, the
      goals of the current investigation were to determine whether there are age
      differences in listening comprehension across the adult lifespan and, if so,
      whether similar trajectories are observed for age-related changes in auditory
      sensitivity and listening comprehension. DESIGN: This study used a cross
      sectional lifespan design in which approximately 60 individuals in each of 7
      decades, from age 20 to 89 yr (a total of 433 participants), were tested on three
      different measures of listening comprehension. In addition, we obtained measures
      of auditory sensitivity from all participants. RESULTS: Changes in auditory
      sensitivity across the adult lifespan exhibited the progressive high-frequency
      loss typical of age-related hearing impairment. Performance on the listening
      comprehension measures, however, demonstrated a very different pattern, with
      scores on all measures remaining relatively stable until age 65 to 70 yr, after
      which significant declines were observed. Follow-up analyses indicated that this
      same general pattern was observed across three different types of passages
      (lectures, interviews, and narratives) and three different question types
      (information, integration, and inference). Multiple regression analyses indicated
      that low-frequency pure-tone average was the single largest contributor to age
      related variance in listening comprehension for individuals older than 65 yr, but
      that age accounted for significant variance even after controlling for auditory
      sensitivity. CONCLUSIONS: Results suggest that age-related reductions in auditory
      sensitivity account for a sizable portion of individual variance in listening
      comprehension that was observed across the adult lifespan. Other potential
      contributors including a possible role for age-related declines in perceptual and
      cognitive abilities are discussed. Clinically, the results suggest that
      amplification is likely to improve listening comprehension but that increased
      audibility alone may not be sufficient to maintain listening comprehension beyond
      age 65 and 70 yr. Additional research will be needed to identify potential target
      abilities for training or other rehabilitation procedures that could supplement
      sensory aids to provide additional improvements in listening comprehension.

PMID- 21716113
TI  - Tinnitus in the general population with a focus on noise and stress: a public
      health study.
AB  - OBJECTIVES: To evaluate the influence of noise and stress on the probability of
      tinnitus in the general population. DESIGN: Questionnaire data were obtained from
      12,166 subjects. RESULTS: Each year of age increased the odds ratio of tinnitus
      by about 3%. Men generally showed a higher risk for tinnitus compared with women.
      Exposure to noise and stress emerged important for the probability of tinnitus.
      However, for the transition from mild to severe tinnitus, stress turned out to be
      especially important. CONCLUSIONS: Stress management strategies should be
      included in hearing conservation programs, especially for individuals with mild
      tinnitus who report a high stress load.

PMID- 21716114
TI  - Does more accurate exposure prediction necessarily improve health effect
      estimates?
AB  - A unique challenge in air pollution cohort studies and similar applications in
      environmental epidemiology is that exposure is not measured directly at subjects'
      locations. Instead, pollution data from monitoring stations at some distance from
      the study subjects are used to predict exposures, and these predicted exposures
      are used to estimate the health effect parameter of interest. It is usually
      assumed that minimizing the error in predicting the true exposure will improve
      health effect estimation. We show in a simulation study that this is not always
      the case. We interpret our results in light of recently developed statistical
      theory for measurement error, and we discuss implications for the design and
      analysis of epidemiologic research.

PMID- 21716116
TI  - Postendoscopic retrograde cholangiopancreatography pancreatitis: a rare cause of
      thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
AB  - Endothelial injury is perhaps the inciting factor leading to the microangiopathic
      process that initiates thrombotic thrombocytopenic purpura-hemolytic uremic
      syndrome (TTP-HUS). TTP-HUS after postendoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis is extremely rare, but potentially
      is life threatening. Here, we describe a case of a 23-year-old man with a history
      of choledocholithiasis, who developed TTP-HUS, 2 days after the onset of post
      ERCP pancreatitis. It is important that physicians recognize TTP-HUS as one of
      the potential causes of acute kidney injury in cases of acute pancreatitis and
      post-ERCP pancreatitis for adult patients, especially when there is concomitant
      thrombocytopenia and hemolytic anemia. The early initiation of plasma exchange
      has a major impact on the survival and preservation of renal function. Exchange
      transfusion of fresh frozen plasma remains the cornerstone treatment of TTP-HUS.

PMID- 21716117
TI  - Prophylactic analgesia before percutaneous liver biopsy: a clinical comparative
      study.
AB  - INTRODUCTION: Liver biopsy remains the gold standard for the diagnosis and
      staging of liver diseases. Despite being painful, analgesia before liver biopsy
      is usually avoided due to the notion that pain is minor and due to the concern of
      masking possible abdominal symptoms. Postbiopsy pain levels were previously
      mapped for the purpose of analgesia planning. AIM: To compare pain and anxiety
      levels between two prophylactic treatment regimens, a combination of sublingual
      tramadol Hcl with oral lorazepam and oral diazepam only. PATIENTS AND METHODS:
      One hundred and thirteen consecutive patients were selected to receive either
      prophylactic analgesia with sublingual tramadol Hcl (50 mg) flashtabs and oral
      lorazepam [(1 mg) analgesia group (AG), n=56] or oral diazepam (5 mg) alone
      [nonAG (NAG), n=57]. Pain and anxiety levels were assessed using Visual Analogue
      Scale (1-10) and State Anxiety Inventory, respectively, 30 min before, and 30 min
      and 6 h after the biopsy. RESULTS: The groups were comparable with respect to
      baseline characteristics. Thirty minutes after the procedure, pain levels were
      significantly lower in the AG (mean Visual Analogue Scale +/- standard error of
      the mean, 1.8 +/- 0. 3; median=1) compared with the NAG (3.1 +/- 0.3, median=3;
      P<0.005). Patients in the NAG (13.8%), reported high pain intensities (>7)
      compared with the patients in the AG (3.6%; P=0.09). Six hours after the
      procedure, pain intensity remained significantly lower in the AG compared with
      the NAG (0.8 +/- 0.1 vs. 1.5 +/- 0.2; P<0.005). Anxiety levels were comparable.
      CONCLUSION: Prophylactic combination of short-acting tramadol and lorazepam is
      effective, safe, and can be used routinely before liver biopsy.

PMID- 21716118
TI  - Is pyogenic liver abscess associated with recurrent pyogenic cholangitis a
      distinct clinical entity? A retrospective analysis over a 10-year period in a
      regional hospital.
AB  - BACKGROUND: Recurrent pyogenic cholangitis (RPC) is recognized as an important
      cause of pyogenic liver abscesses (PLA). Although it is endemic to Southeast
      Asia, it is seen increasing in the west mainly owing to immigration. The aim of
      this study is to compare the clinical characteristics of PLA in patients with RPC
      and without RPC. METHODS: We performed a retrospective analysis involving
      patients with PLA. The demographic, clinical features, laboratory and imaging
      findings, management strategy, and outcome of patients with and without RPC were
      studied. RESULTS: From January 2000 to December 2009 inclusive, 319 patients (27
      with RPC and 292 without RPC) had PLA. Patients with RPC had higher mean age
      (71.7 vs. 64.9 years; P=0.03) and tended to have more acute onset of presentation
      than it did in those without RPC. The common clinical features of the two groups
      were fever, chill, and right upper quadrant pain. Patients without RPC tended to
      have more respiratory symptoms and signs. The laboratory abnormalities of both
      groups shared common features such as anemia, leukocytosis, high erythrocyte
      sedimentation rate and C-reactive protein, hypoalbuminemia, elevated total
      bilirubin, and alanine aminotransferase. Left lobe was predominantly involved in
      patients with RPC (51.9% vs. 23.6%; P<0.01) whereas those without RPC usually had
      PLA at right lobe (67.5 vs. 40.7%; P<0.01). Both groups also shared common
      radiological features such as hypoechoic in ultrasonograpphy, rim enhancement and
      septal lobulation in computed tomography. However, aerobila was found more in
      patients with RPC than those without RPC (25.9 vs. 5.5%; P<0.01) and the latter
      tended to have more abscess ruptures. The biliary tract disorder was the most
      common cause of the disease in the two groups. The microorganisms involved had
      distinct patterns between these two groups. Patients with RPC tended to have
      fewer complications than patients without RPC as there were fewer occurrences in
      metastatic infections, disseminated intravascular coagulation, and acute renal
      and respiratory failure. PLA in patients with RPC had higher recurrence rate than
      those without RPC (37 vs. 2.4%; P<0.01). The odds ratio of local recurrence
      between RPC and non-RPC group was 23.95 (95% confidence interval, 8.11-70.72).
      However, both were effectively managed by the combination of antibiotic and image
      guided aspiration with/without drainage, and their mortality rates are comparable
      with each other. CONCLUSION: PLA associated with RPC tends to have distinct
      clinical syndrome in regards to different extent of clinical manifestations,
      radiological and microbiological features, and complications. Its recurrent rate
      is higher than that of non-RPC type. However, both can be effectively treated
      with a combination of antibiotic and image-guided aspiration with/without
      drainage.

PMID- 21716119
TI  - What questions should newborn screening long-term follow-up be able to answer? A
      statement of the US Secretary for Health and Human Services' Advisory Committee
      on Heritable Disorders in Newborns and Children.
AB  - The US Secretary of Health and Human Services' Advisory Committee on Heritable
      Disorders in Newborns and Children provides guidance on reducing the morbidity
      and mortality associated with heritable disorders detectable through newborn
      screening. Efforts to systematically evaluate health outcomes, beyond long-term
      survival, with a few exceptions, are just beginning. To facilitate these nascent
      efforts, the US Secretary of Health and Human Services' Advisory Committee on
      Heritable Disorders in Newborns and Children initiated a project to define the
      major overarching questions to be answered to assure that newborn screening is
      meeting its goal of achieving the best quality outcome for the affected children
      and their families. The questions identified follow the central components of
      long-term follow-up-care coordination, evidence-based treatment, continuous
      quality improvement, and new knowledge discovery-and are framed from the
      perspectives of the state and nation, primary and specialty healthcare providers,
      and the impacted families. These overarching questions should be used to guide
      the development of long-term follow-up data systems, quality health indicators,
      and specific data elements for evaluating the newborn screening system.

PMID- 21716120
TI  - ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of
      focal hyperinsulinemic hypoglycemia.
AB  - PURPOSE: Congenital hyperinsulinism of infancy (OMIM# 256450) is a devastating
      disease most commonly caused by dominant or recessive mutations in either ABCC8
      or KCNJ11, the genes that encode for the beta-cell adenosine triphosphate
      regulated potassium channel. A unique combination of a paternally inherited
      germline mutation and somatic loss-of-heterozygosity causes the focal form of the
      disease (Focal-congenital hyperinsulinism of infancy [Focal-CHI]), the incidence
      of which in genetically susceptible individuals is not known. METHODS: We
      genotyped 21,122 Ashkenazi Jewish individuals for two previously identified ABCC8
      founder mutations and utilized a clinical database of 61 unrelated Ashkenazi
      patients with congenital hyperinsulinism of infancy to obtain an estimate of the
      risk of Focal-CHI in a genetically susceptible fetus. RESULTS: The combined
      mutation carrier rate in Ashkenazi Jews was 1:52, giving an estimated frequency
      of homozygosity or compound heterozygosity of 1:10,816 in this population. The
      risk of Focal-CHI is 1:540 per pregnancy in offspring of carrier fathers.
      CONCLUSION: We recommend that these mutations be included in the genetic
      screening program for the Ashkenazi Jewish population. As the risk of Focal-CHI
      is not expected to be mutation specific, the data reported in this study are
      useful for counseling all families in which the father was found to carry a
      recessive ABCC8 or KCNJ11 mutation.

PMID- 21716121
TI  - Chromosomal microarray testing influences medical management.
AB  - PURPOSE: Chromosomal microarray (CMA) testing provides the highest diagnostic
      yield for clinical testing of patients with developmental delay (DD),
      intellectual disability (ID), multiple congenital anomalies (MCA), and autism
      spectrum disorders (ASD). Despite improved diagnostic yield and studies to
      support cost-effectiveness, concerns regarding the cost and reimbursement for CMA
      have been raised because it is perceived that CMA results do not influence
      medical management. METHODS: We conducted a retrospective chart review of CMA
      testing performed during a 12-month period on patients with DD/ID, ASD, and
      congenital anomalies to determine the proportion of cases where abnormal CMA
      results impacted recommendations for clinical action. RESULTS: Among 1792
      patients, 13.1% had clinically relevant results, either abnormal (n = 131; 7.3%)
      or variants of possible significance (VPS; n = 104; 5.8%). Abnormal variants
      generated a higher rate of recommendation for clinical action (54%) compared with
      VPS (34%; Fisher exact test, P = 0.01). CMA results influenced medical care by
      precipitating medical referrals, diagnostic imaging, or specific laboratory
      testing. CONCLUSIONS: For all test indications, CMA results influenced medical
      management in a majority of patients with abnormal variants and a substantial
      proportion of those with VPS. These results support the use of CMA as a clinical
      diagnostic test that influences medical management for this patient population.

PMID- 21716122
TI  - Simple scoring system predicting genotypic resistance during rescue therapy for
      Lamivudine-resistant chronic hepatitis B.
AB  - GOAL: In this study, we aimed to devise a simple scoring system predicting the
      risk of genotypic resistance (GR) to current rescue therapies for patients with
      lamivudine (LAM)-resistant chronic hepatitis B. BACKGROUND: LAM and adefovir
      (ADV) combination therapy should be recommended for an initial rescue therapy
      against LAM-resistant hepatitis B virus (HBV). However, there still are many LAM
      resistant patients being treated with entecavir (ETV) or ADV monotherapy. STUDY:
      This retrospective cohort study included consecutive patients treated for LAM
      resistant chronic hepatitis B with ETV or ADV monotherapy, or LAM/ADV combination
      therapy. The cumulative probabilities of GR and virological responses and
      breakthrough according to clinical variables were analyzed by survival analyses
      and derived an index for future GR. RESULTS: A total of 224 patients were
      included (median treatment duration=117.9 wk). Using risk factors indentified on
      multivariable analyses, a simple index for future GR (Antiviral Resistance
      Prediction Index, ARPI) was developed with 3 clinical variables: the rescue
      therapy regimens (+0, ADV; +1, ETV; +2, LAM/ADV), HBV DNA reduction at 12 weeks
      (+0, <3 log10 copies/mL; +1, >3 log10 copies/mL), and the initial HBV DNA level
      (+0, >10 copies/mL; +1, <10 copies/mL). No patient with ARPI >=2 exhibited GR,
      whereas 47% of the patients with an ARPI <2 developed GR by week 144 (P=0.005).
      CONCLUSIONS: The results of this study suggest that the ARPI is a simple and
      early index that can be used to determine the risk for subsequent GR during
      rescue therapy for LAM-resistant chronic hepatitis B.

PMID- 21716123
TI  - How patients view probiotics: findings from a multicenter study of patients with
      inflammatory bowel disease and irritable bowel syndrome.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) and irritable bowel
      syndrome (IBS) have access to a growing number of probiotic products marketed to
      improve digestive health. It is unclear how patients make decisions about
      probiotics and what role they expect their gastroenterologists to play as they
      consider using probiotics. Understanding patients' knowledge, attitudes and
      expectations of probiotics may help gastroenterologists engage patients in
      collaborative discussions about probiotics. STUDY: Focus groups were conducted
      with patients with IBD and IBS at the Cleveland Clinic, Mayo Clinic, and Johns
      Hopkins University. Inductive analytic methods were used to identify common
      themes and draw interpretations from focus group narratives. RESULTS: One hundred
      thirty-six patients participated in 22 focus groups between March and August
      2009. Patients viewed probiotics as an appealing alternative to pharmaceutical
      drugs and understood probiotics as a more "natural," low-risk therapeutic option.
      Many patients were hesitant to use them without consulting their
      gastroenterologists. Patients would weigh the risks and benefits of probiotics,
      their disease severity and satisfaction with current treatments when considering
      probiotic use. CONCLUSIONS: Patients are interested in probiotics but have many
      unanswered questions about their use. Our findings suggest that patients with IBD
      and IBS will look to gastroenterologists and other clinicians as trustworthy
      advisors regarding the utility of probiotics as an alternative or supplement to
      pharmaceutical drugs. Gastroenterologists and other clinicians who care for
      patients with these diseases should be prepared to discuss the potential benefits
      and risks of probiotics and assist patients in making informed decisions about
      their use.

PMID- 21716124
TI  - Endoscopic fecal microbiota transplantation: "first-line" treatment for severe
      clostridium difficile infection?

PMID- 21716125
TI  - Diffusion-weighted magnetic resonance imaging for the staging of liver fibrosis.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance (MR) imaging (DWI) has been
      suggested for staging liver fibrosis. The aim of this study was to evaluate the
      diagnostic accuracy of DWI for the noninvasive assessment of hepatic fibrosis.
      METHODS: We retrospectively compared DWI from clinically acquired MR scans with
      histologic methods. Liver biopsy specimens were staged F0-F4 in accordance with
      the METAVIR score. Hepatic steatosis was classified on a 5-point scale. Hepatic
      iron was graded on a 3-point scale. Liver inflammation was scored according to
      the modified hepatic activity index. Nonparametric methods, linear regression
      models, and receiver operating characteristic analyses were used to determine
      diagnostic accuracy and apparent diffusion coefficient (ADC) cutoff values.
      RESULTS: Liver ADC values were inversely correlated with fibrosis stage: P = 
      0.54 (P < 0.0001). Although there was substantial overlap in the ADC
      distributions, the differences in ADC values by METAVIR stages F0 versus (vs.) F1
      4, F0-1 versus F > 1, F0-2 versus F3-4 and F0-3 versus F4 were all significant.
      For prediction of fibrosis stage 1, stage 2, stage 3, and stage 4 area under the
      receiver operating characteristic curve of 0.79, 0.77, 0.77, and 0.79 were
      obtained, respectively. Inflammation also correlated significantly with ADC
      values (P = -0.23, P = 0.03), but iron content (P = 0.17) or steatosis (P = 0.63)
      did not correlate with ADC measurements. CONCLUSIONS: Liver ADC can be used to
      predict liver fibrosis with acceptable diagnostic accuracy. DWI should be
      included in further prospective studies to validate a comprehensive MR imaging
      protocol for the noninvasive assessment of hepatic fibrosis.

PMID- 21716126
TI  - Central blood pressure, arterial waveform analysis, and vascular risk factors in
      glaucoma.
AB  - PURPOSE: Reduced ocular perfusion pressure has been linked to glaucoma, and
      increased arterial stiffness is implicated in systemic cardiovascular risk. This
      study measured central blood pressure (BP) and arterial waveforms derived from
      pulse tonometry, together with data on systemic and ocular vascular factors
      relevant to glaucoma status. METHODS: A total of 126 patients and 66 normal
      controls were tested, including 90 primary open-angle glaucoma (POAG) patients
      and 36 normal tension glaucoma (NTG) patients. Glaucoma patients had been
      followed for at least 3 years and inclusion required several (>4) reliable visual
      fields such that glaucoma progression could be determined. Radial pulse tonometry
      and brachial BP data were collected, together with data on disc hemorrhages,
      spontaneous venous pulsation, peripapillary atrophy, smoking, and medications.
      RESULTS: Brachial BP or derived central aortic BP parameters generally showed no
      significant differences between glaucoma patients and normal individuals. The
      POAG group had a lower pulse pressure, which was also significant in the
      regression analysis (P<0.002). In the arterial waveform analysis, POAG was
      associated with a lower brachial form factor than NTG (P<0.001) and higher
      subendocardial viability ratio (P<0.008). NTG was associated with a lower body
      mass index, and POAG with a smoking history. There was an increased incidence of
      disc hemorrhages and a reduced incidence of spontaneous venous pulsations in the
      progressing group. CONCLUSIONS: Derived central BP does not reveal significant
      differences from controls or in glaucoma subgroups, but a reduced pulse pressure
      was identified. There may be some changes in arterial pulse waveform shape
      suggesting possible differences in diastolic perfusion. Disc hemorrhages and loss
      of spontaneous venous pulsation were associated with disease progression.

PMID- 21716127
TI  - Effect of beclomethasone nasal spray on intraocular pressure in ocular
      hypertension or controlled glaucoma.
AB  - PURPOSE: To evaluate the effect of 6 weeks administration of beclomethasone nasal
      spray on intraocular pressure (IOP) in patients with ocular hypertension or
      controlled primary open-angle glaucoma. PATIENTS AND METHODS: Randomized double
      masked controlled trial. Patients were randomized to twice daily beclomethasone
      versus placebo saline nasal spray. There were a total of 4 study visits: baseline
      and weeks 2, 4, 6 after starting the spray. Each study visit was at the same time
      within a 1-hour time window. Primary outcome measure was IOP. Secondary measures
      included visual acuity, anterior segment changes, patient reported side effects,
      and compliance. Study endpoint was 6 weeks from the start of treatment or an IOP
      increase of >20% from baseline. A sample size calculation suggested that 8
      patients in each arm would be sufficient to detect a difference of 3.2 mm Hg with
      a power of 80%. RESULTS: Nineteen consecutive consenting patients completed the
      study-9 in the steroid arm and 10 in the placebo arm. There were no statistically
      significant differences between groups in baseline characteristics, IOP at each
      study visit, or change in IOP from baseline at any time point. At 6 weeks, the
      change in mean IOP from baseline was +0.50+/-1.52 versus +0.70+/-1.44 mm Hg in
      the steroid and saline nasal spray groups, respectively (P=0.77). CONCLUSIONS:
      Patients with ocular hypertension and primary open-angle glaucoma showed no
      evidence of IOP elevation after 6 weeks use of beclomethasone nasal spray.

PMID- 21716128
TI  - Prostaglandin I2 analogs suppress tumor necrosis factor alpha production and the
      maturation of human monocyte-derived dendritic cells.
AB  - BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells and
      have critical roles in regulating immune responses. Prostaglandin I2 (PGI2)
      analogs are considered to be potential treatments for asthma. However, the effect
      of PGI2 analogs on human monocyte-derived DCs (MDDCs) is still not clearly
      understood. METHODS: Human MDDCs were pretreated with iloprost and treprostinil
      (2 PGI2 analogs) or forskolin (an adenyl cyclase activator) before
      lipopolysaccharide (LPS) stimulation. In some cases, I prostanoid (IP) receptor
      and E prostanoid receptor antagonists were added before the PGI2 analog
      treatment. tumor necrosis factor alpha (TNF-alpha) was measured by enzyme-linked
      immunosorbent assay. The expression of costimulatory molecules was assessed by
      flow cytometry. T-cell polarization function was investigated by measuring
      interferon gamma, interleukin 13 (IL-13), and IL-17A production by T cells
      cocultured with iloprost-treated MDDCs. RESULTS: Iloprost and treprostinil
      suppressed LPS-induced TNF-alpha expression in MDDCs. This effect could be
      reversed by an IP receptor antagonist, CAY10449, but not by E prostanoid receptor
      antagonists. Forskolin conferred a similar effect. Iloprost suppressed the LPS
      induced expression of costimulatory molecules, including CD80, CD86, CD40, and
      HLA-DR. Iloprost-treated MDDCs increased IL-17A production by T cells.
      CONCLUSIONS: Prostaglandin I2 analogs may exert anti-inflammatory effects by
      suppressing TNF-alpha expression via the IP receptor-cyclic adenosine
      monophosphate pathways and by inhibiting the expression of costimulatory
      molecules in human MDDCs.

PMID- 21716129
TI  - Improving erythropoietin-stimulating agent administration in a multihospital
      system through quality improvement initiatives: a pre-post comparison study.
AB  - INTRODUCTION: : Erythropoietin-stimulating agent (ESA) use is associated with
      serious adverse events in patients with hemoglobin levels of 12 g/dL or higher at
      the time of administration. Our aim was to determine whether inappropriate ESA
      use has changed over time since the implementation of new drug warning alerts and
      local quality improvement initiatives. MATERIALS AND METHODS: : We performed a
      retrospective review of ESA administration practices at Memorial Hermann
      Healthcare System (Houston, Tex). Our primary outcome measure was the proportion
      of inpatient encounters (one entire inpatient hospital stay) with 1 or more
      inappropriate uses of ESA (defined as ESA administration for a patient with
      hemoglobin >=12 g/dL). We analyzed the potential influence of local and national
      interventions on ESA utilization patterns. RESULTS: : Between May 1, 2006, and
      May 31, 2009, 15,642 inpatients were treated with ESAs in our system. We
      classified inpatients as before intervention (n = 6350) and after intervention (n
      = 9292) based on the date of implementation of a synchronous alert in the
      electronic medical record. We found a significant decrease in inappropriate ESA
      administration before to after intervention (9.03%-6.21%; P < 0.001), which can
      be translated into a 31.25% (05% CI, 21.93%-40.75%) relative risk reduction.
      Reduced odds ratios for inappropriate ESA use changed little after controlling
      for relevant demographic variables and clinical characteristics. CONCLUSIONS: :
      Following several quality improvement interventions to improve patient safety
      related to ESA use, we found a significant reduction in inappropriate ESA
      administration to inpatients in a large health care system.

PMID- 21716130
TI  - Pharmacokinetics and safety of dexlansoprazole MR in adolescents with symptomatic
      GERD.
AB  - OBJECTIVES: Dexlansoprazole MR 30  mg once daily (QD) is approved in adults for
      the treatment of symptomatic nonerosive gastroesophageal reflux disease (GERD)
      and maintenance of healed erosive esophagitis (EE); 60  mg is approved for
      healing EE. The present study assesses the pharmacokinetic (PK) profile and
      safety of dexlansoprazole MR in adolescent patients. PATIENTS AND METHODS: Phase
      1, open-label, parallel-group, multicenter study in male and female adolescents
      (12-17 years) with GERD. Patients were randomized to receive dexlansoprazole MR
      (30 or 60  mg, QD) for 7 days. Blood samples to determine dexlansoprazole plasma
      concentrations were drawn over a 24-hour period after dosing on day 7.
      Dexlansoprazole plasma concentrations and PK parameters were summarized by dose
      group. Safety assessments included monitoring of adverse events (AEs). RESULTS:
      Thirty-six patients (mean age 14.6 years), 14 boys and 22 girls, were randomized,
      with PK data available for 35 patients. The overall exposure of dexlansoprazole
      after administration of the 60-mg capsule was slightly less than double the
      exposure from the 30-mg capsule. Cmax (691 and 1136  ng/mL) and area under the
      plasma concentration time curve (2886 and 5120  ng . h/mL) values for the 30- and
      60-mg doses, respectively, were similar to results from previous phase 1 studies
      in healthy adults. Twelve of 36 patients (33.3%) experienced a total of 21
      treatment-emergent AEs. All of the AEs were considered to be of mild severity.
      CONCLUSIONS: The PK data for dexlansoprazole MR 30- and 60-mg capsules in
      adolescent patients with symptomatic GERD were similar to those in healthy
      adults. Both doses were well tolerated.

PMID- 21716131
TI  - Unusual case of hypothyroidism in an infant with hepatic hemangioma.

PMID- 21716132
TI  - Predictive effect of serial serum alanine aminotransferase levels on spontaneous
      HBeAg seroconversion in chronic genotype B and C HBV-infected children.
AB  - OBJECTIVE: The present study aimed to investigate the association between serial
      serum alanine aminotransferase (ALT) and spontaneous hepatitis B e antigen
      (HBeAg) seroconversion age in chronic hepatitis B virus (HBV)-infected children.
      PATIENTS AND METHODS: One hundred four HBeAg-positive chronic genotype B or C HBV
      infected patients were included in this long-term prospective cohort study (mean
      initial age 7.20 years). Serial serum ALT levels and HBV serology markers were
      measured every 6 to 12 months. The 104 subjects made a total of 2525 visits
      during the study period, and the majority (93.6%) of visits were within a 1-year
      interval apart from previous visits. Cox proportional hazards model with time
      dependent covariates was used in the survival analysis of HBeAg in these
      subjects. RESULTS: During the chronic course of HBV infection, the median
      remaining times to spontaneous HBeAg seroconversion were 8.35, 5.14, 4.25, 3.95,
      and 2.80 years after the ALT levels crossed 20, 30, 40, 60, and 150 IU/L,
      respectively. The incidence rate of spontaneous HBeAg seroconversion within 6
      months when a subject entered the phase of ALT between 60 and 150 IU/L was 5.57
      times that of the phase with ALT < 60 IU/L. The incidence rate of HBeAg
      seroconversion once ALT levels were above 150 IU/L was 9.87 times that of the
      phase of ALT < 60 IU/L. CONCLUSIONS: The ALT levels above 30 IU/L served as a
      cutoff of the inflammatory phase in chronic genotype B and C HBV-infected
      patients. Serial ALT levels in chronic HBV-infected subjects offer a predicted
      effect on the occurrence of spontaneous HBeAg seroconversion.

PMID- 21716133
TI  - Coeliac disease diagnosis: ESPGHAN 1990 criteria or need for a change? Results of
      a questionnaire.
AB  - BACKGROUND AND OBJECTIVES: A revision of criteria for diagnosing coeliac disease
      (CD) is being conducted by The European Society for Pediatric Gastroenterology,
      Hepatology, and Nutrition (ESPGHAN). In parallel, we have performed a survey
      aimed to evaluate present practices for CD among paediatric gastroenterologists
      and to learn their views on the need for modification of present criteria for CD
      diagnosis. PATIENTS AND METHODS: Questionnaires were distributed to experienced
      paediatric gastroenterologists (ESPGHAN members) via the Internet. RESULTS:
      Overall, 95 valid questionnaires were available for analysis, pertaining to 28
      different countries, with the majority of responders treating patients with CD
      for >15 years. Only about 12% of the responders comply with present criteria,
      noncompliance being related mainly to the challenge policy. Approximately 90%
      request a revision and modification of the present criteria. Forty-four percent
      want to omit the small bowel biopsy in symptomatic children with positive anti
      tissue transglutaminase immunoglobulin (Ig) A or endomysial IgA antibodies,
      especially if they are DQ2/DQ8 positive. For silent cases detected by screening
      with convincingly positive anti-tissue transglutaminase IgA or EMA IgA, about 30%
      consider that no small bowel biopsy should be required in selected cases. Adding
      human leukocyte antigen typing in the diagnostic workup was asked for by 42% of
      the responders. As for gluten challenge, a new policy is advocated restricting
      its obligation to cases whenever the diagnosis is doubtful or unclear.
      CONCLUSIONS: Based on these opinions, revision of the ESPGHAN criteria for
      diagnosing CD is urgently needed.

PMID- 21716134
TI  - Phenotypic and genotypic differences between a child with vertically acquired
      severe hepatitis C liver disease and his mother.

PMID- 21716135
TI  - Early-onset hepatic fibrosis in lysinuric protein intolerance.

PMID- 21716136
TI  - Red blood cell morphology reporting:  additional views.

PMID- 21716137
TI  - Primary cerebral myxofibrosarcoma: clinical, morphologic, immunohistochemical,
      molecular, and ultrastructural study of an infrequent tumor in an extraordinary
      localization.
AB  - Herein, we describe an intracerebral primary low-grade myxofibrosarcoma occurring
      in a 9-year-old boy. The lesion measured 7 cm and occupied the left parieto
      occipital region. A gross-total removal of the tumor was performed. Nine months
      later, radiologic follow-up revealed a local recurrence which was again
      surgically removed. The patient then underwent radiotherapy and chemotherapy. He
      was well and disease-free at 6 months follow-up. The tumor was composed of
      spindle, stellated, and multinucleated cells embedded in a myxoid background.
      Foci of increased cellularity, pleomorphism, and high mitotic rate were present.
      The tumor borders were sharply demarcated from the non-neoplastic nervous
      parenchyma. Immunohistochemical staining showed that the neoplastic cells were
      vimentine and CD34 positive. Fluorescence in-situ hybridization analyses did not
      show FUS and EWSR1 gene rearrangements. Primary intracranial myxofibrosarcomas
      are very rare (to the best of our knowledge, less than 10 published cases in the
      international literature). We believe each new case should be recorded to produce
      a better clinical, pathologic, molecular, prognostic, and therapeutic
      characterization of this lesion.

PMID- 21716138
TI  - Uncommon presentation of rare disorder-duodenal ulcer secondary to invasive
      pancreatic primitive neuroectodermal tumor: case report and review of the
      literature.
AB  - The authors report an unusual presentation of a rare tumor in childhood, a
      pancreatic primitive neuroectodermal tumor invading the duodenum leading to
      anemia. A review of intra-abdominal primitive neuroectodermal tumors is
      discussed.

PMID- 21716139
TI  - Institutional experience with clofarabine and cytarabine in relapsed pediatric
      acute myeloid leukemia.
AB  - Cytarabine (1000 mg/m/d intravenous for 5 d) and clofarabine (40 mg/m/d
      intravenous for 5 d) were given every 28 days to 9 children with relapsed acute
      myeloid leukemia at our institution. Among 19 courses, there were 18 infectious
      episodes. Median hospitalization time was 13 days (7.7 to 30.5 d) per cycle.
      Hepatobiliary abnormalities included alanine aminotransferase/aspartate
      aminotransferase elevation and hyperbilirubinemia. Four patients achieved
      complete remission (one after an earlier allogeneic Haematopoietic Progenitor
      Cell Transplant). Four patients are alive disease free. In summary, a proportion
      of children responded and was able to receive allogeneic Haematopoietic
      Progenitor Cell Transplant. Side effects were tolerable, although hospitalization
      time was prolonged.

PMID- 21716140
TI  - A modified surgical technique for neglected fracture of lateral humeral condyle
      in children.
AB  - Operative treatment for neglected fracture of lateral humeral condyle (LHC) is
      difficult because of contracted muscle, fibrous tissue formation, and indistinct
      bony edges. Its success depends on the ability to preserve blood supply during
      the surgery. We retrospectively reviewed eight cases of neglected fracture of LHC
      in children treated with open reduction with selected multiple 'V' lengthening of
      common extensor muscle and internal fixation. The patients were between 3 and 8
      years of age. The period of neglect was between 3 and 20 weeks. Four patients
      with displacement of more than 10 mm and neglect for 5 weeks or more required
      lengthening of common extensor muscle aponeurosis. The follow-up assessments were
      between 1 and 6.3 years with a mean of 4.4 years. All patients had union by 2
      months. They gained improvement of flexion range of motion between 60 degrees 
      and 120 degrees  with a mean of 86.3 degrees . Loss of final range of motion
      compared with the normal side was between 5 degrees  and 35 degrees  with a mean
      of 10 degrees . No patient had limitation of activities or pain. Six cases had
      excellent and two cases had good Dillon functional score. All patients had
      lateral condyle prominent with different severities. There was one mild avascular
      necrosis and one fishtail deformity. Both of them had almost full range of
      motion. All patients had early physeal closure, except one, who had only 1 year
      follow-up. There was no case of progressive valgus deformity. Children with
      neglected fracture of LHC would benefit from anatomical reduction and internal
      fixation through a proper exposure and if indicated combined with multiple 'V'
      lengthening of common extensor muscle aponeurosis. This is a level IV study.

PMID- 21716141
TI  - Osteogenesis imperfecta misdiagnosed as child abuse.
AB  - The differential diagnosis of child abuse includes osteogenesis imperfecta (OI).
      Mild phenotypes of OI may be misdiagnosed as child abuse. The purpose of this
      study was to review the experience of families in which OI was misdiagnosed as
      child abuse. Sixty-one potential cases of misdiagnosis were identified from a lay
      support organization. Upon review of the medical records, 33 cases were
      identified with a confirmed diagnosis of OI (skin biopsy or DNA blood test).
      Questionnaires were given to families to describe their condition and
      experiences. There were 19 male and 14 female children. Mean age at presentation
      was 7.1 months (range: 1-23 months). All patients had fractures and the
      presenting symptoms included pain (n=14), swelling (n=7), decreased limb movement
      (n=5), or unusual limb position (n=2). Abnormal radiograph findings consistent
      with OI were found in 19 of 33 patients (58%), clinical findings of OI were
      present in 23 of 33 patients (70%), and a family history that could be supportive
      of OI was present in 18 of 33 families (55%). Children were removed from the
      family in 70% of cases and older siblings were removed from the family in 62% of
      cases. The mean age at the time of diagnosis of OI was 10.5 months (range: 3-35
      months). The consequences of misdiagnosis of OI as child abuse are devastating to
      the family. OI should be considered in all cases of suspected child abuse. In
      children with any clinical, radiographic, or family history features of OI, early
      involvement of a bone specialist and performance of laboratory testing should be
      considered to establish a timely and accurate diagnosis.

PMID- 21716142
TI  - Stand-alone anterior versus anteroposterior lumbar interbody single-level fusion
      after a mean follow-up of 41 months.
AB  - STUDY DESIGN: Prospective cohort study comparing evaluations of single-level
      anterior lumbar interbody fusion (ALIF) versus anteroposterior lumbar fusion
      (APLF). OBJECTIVE: To clinically and radiologically compare the outcome after
      angle-stable, locked, stand-alone ALIF with that obtained after APLF, in cases
      with degenerative disc disease (DDD). SUMMARY OF BACKGROUND DATA: Fusion rates
      have been reported to be highest after interbody fusion with transpedicular
      fixation. However, transpedicular fixation is linked to significant damage of the
      paravertebral muscles, to screw displacement-related neurological and vascular
      complications, and to an increased rate of adjacent segment degeneration. When
      performed as a stand-alone procedure, the disadvantages of transpedicular
      fixation can be completely avoided by ALIF. METHODS: Eighty patients with chronic
      low-back pain due to a single-level DDD (Modic >=2) and facet joint arthritis
      (Fujiwara >=3) were enrolled in this study. Forty patients received an
      anteroposterior fusion (ALIF with transpedicular fixation: APLF group) and 40
      patients (ALIF group) were treated with a stand-alone ALIF using the Synfix-LR
      device. At 7 days, 3, 6, 12, and 24 months, and at a mean follow-up of 41 months,
      patients were clinically (visual analog scale, Oswestry Low Back Pain Disability
      Index, satisfaction) and radiologically (x-ray, and at 12 months, thin-slice
      computed tomography) compared. RESULTS: Blood loss and duration of surgery were
      significantly lower in the ALIF group (P<0.001). Visual analog scale and Oswestry
      Low Back Pain Disability Index improved significantly over time (analysis of
      variance, P<0.001) in both groups, but both scores were significantly better in
      ALIF group (analysis of variance, P<0.001). Patients' satisfaction consistently
      ranked higher in the ALIF group (P=0.042 at 12 mo). No significant difference was
      found in the fusion rate throughout the study. CONCLUSIONS: Stand-alone ALIF
      leads to better clinical results than APLF, without differences in fusion rates
      after 41 months. Therefore, when a posterior approach is not needed for
      decompression or reposition, we suggest performing a stand-alone ALIF in cases
      with single-level DDD.

PMID- 21716143
TI  - Bortezomib for patients with advanced-stage bronchioloalveolar carcinoma: a
      California Cancer Consortium Phase II study (NCI 7003).
AB  - BACKGROUND: Bronchioloalveolar carcinoma (BAC), a subtype of non-small cell lung
      cancer, is a difficult disease to treat with low response rates with cytotoxic
      chemotherapy. Bortezomib, a proteasome inhibitor, has demonstrated objective
      responses in patients with BAC in early-phase clinical trials. We conducted a
      phase II study of bortezomib in patients with advanced-stage BAC. METHODS:
      Patients with advanced BAC, adenocarcinoma with BAC features or BAC with
      adenocarcinoma features, and less than two prior regimens were eligible. Prior
      epidermal growth factor receptor (EGFR) inhibitor therapy was allowed. Bortezomib
      was administered intravenously at 1.6 mg/m on days 1 and 8 of every 21-day cycle
      until disease progression or unacceptable toxicity. The primary end point was
      response rate. The Simon two-stage design was used. RESULTS: Forty-two patients
      were enrolled, and the study was halted early for slow accrual. Patient
      characteristics were female 55%, median age 68 years, and Eastern Cooperative
      Oncology Group performance status of 0 and 1 in 31 and 11 patients, respectively.
      Twenty-six (62%) patients had received prior therapy with an EGFR inhibitor. A
      median of four cycles of therapy were administered. Objective responses were
      noted in 5%, whereas 57% had disease stabilization. The median progression-free
      survival and overall survival were 5.5 and 13.6 months, respectively. Grade 3
      diarrhea and fatigue were noted in three and five patients, respectively.
      CONCLUSIONS: Bortezomib is tolerated well and is associated with modest
      anticancer activity in patients with advanced BAC, including patients who
      progressed on EGFR inhibitor therapy.

PMID- 21716144
TI  - MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential
      antitumor effects in non-small cell lung cancer according to MET alterations.
AB  - INTRODUCTION: Tyrosine kinase inhibitors (TKIs) targeted to MET are undergoing
      clinical trials in patients with solid tumors, but the precise mechanism of the
      antitumor activity of these drugs remains unclear. We examined the antitumor
      action of the MET-TKI crizotinib (PF-02341066) in lung cancer cells that are
      positive or negative for MET amplification or mutation. METHODS: The antitumor
      action of crizotinib was evaluated on the basis of signal transduction, cell
      proliferation, apoptosis, and progression of tumor xenografts. RESULTS:
      Inhibition of MET signaling by crizotinib or by RNA interference-mediated MET
      depletion resulted in the induction of apoptosis accompanied by inhibition of AKT
      and extracellular signal-regulated kinase phosphorylation in lung cancer cells
      with MET amplification but not in cells with a MET mutation or in those without
      amplification or mutation of MET. These results suggest that MET signaling is
      essential for the survival of cells with MET amplification but not for that of
      cells without this genetic change, including those with a MET mutation.
      Crizotinib up-regulated the expression of BIM, a proapoptotic member of the Bcl-2
      family, and down-regulated that of survivin, a member of the inhibitor of
      apoptosis protein family, in cells with MET amplification. Forced depletion of
      BIM and expression of survivin each inhibited crizotinib-induced apoptosis,
      suggesting that both up-regulation of BIM and down-regulation of survivin
      contribute to the proapoptotic effect of crizotinib. CONCLUSIONS: Crizotinib
      shows a marked antitumor action in MET amplification-positive lung cancer cells
      but not in cells without MET amplification, including those with a MET mutation.

PMID- 21716145
TI  - The role of extended cervical mediastinoscopy in staging of non-small cell lung
      cancer of the left lung and a comparison with integrated positron emission
      tomography and computed tomography: does integrated positron emission tomography
      and computed tomography reduce the need for invasive procedures?
AB  - OBJECTIVE: Extended cervical mediastinoscopy (ECM) is a method for sampling
      aortopulmonary window (APW) mediastinal lymph nodes. In this study, the efficacy
      of integrated positron emission tomography/computed tomography (PET/CT) was
      compared with ECM for the detection of APW lymph node metastasis. METHODS: Fifty
      five patients diagnosed of non-small cell lung cancer in whom APW or hilar lymph
      nodes had been reported to be positive on PET/CT, and/or who had had central
      tumor and/or in whom ECM had been performed for mediastinal staging due to the
      presence of APW lymph nodes larger than 1 cm in diameter on the CT between 2005
      and 2009, were retrospectively analyzed. All patients underwent PET/CT scanning.
      RESULTS: Thirty-eight patients were identified as cN0 by standard cervical
      mediastinoscopy/ECM, and lobectomy, pneumonectomy, and exploratory thoracotomy
      were performed on 19, 13, and six of these patients, respectively. Mediastinal
      lymphadenectomy revealed APW lymph node metastases in four patients (ECM false
      negative). Seventeen patients identified as cN2 by mediastinoscopy, APW lymph
      node metastasis was present in nine, whereas eight had mediastinal lymph node
      metastasis that could only be accessed by standard cervical mediastinoscopy but
      had no APW lymph node metastasis were excluded from the analysis. Sensitivity,
      specificity, negative predictive value, positive predictive value, and accuracy
      of ECM/PET/CT were calculated as 0.69/0.53, 1/0.91, 0.89/0.83, 1/0.70, and
      0.91/0.80, respectively. CONCLUSIONS: ECM, which is an effective technique used
      in the determination of APW lymph node metastasis, was enough to rule out nodal
      disease with negative predictive value. PET/CT does not reduce the need for
      invasive procedures in detecting APW lymph node metastasis.

PMID- 21716146
TI  - A randomized phase II trial of first-line treatment with gemcitabine, erlotinib,
      or gemcitabine and erlotinib in elderly patients (age >=70 years) with stage
      IIIB/IV non-small cell lung cancer.
AB  - INTRODUCTION: Single-agent gemcitabine is a standard of care for elderly patients
      with advanced non-small cell lung cancer, but novel therapies are needed for this
      patient population. METHODS: We performed a noncomparative randomized phase II
      trial of gemcitabine, erlotinib, or the combination in elderly patients (age >=70
      years) with stage IIIB or IV non-small cell lung cancer. Patients were randomized
      to arms: A (gemcitabine 1200 mg/m on days 1 and 8 every 21 days), B (erlotinib
      150 mg daily), or C (gemcitabine 1000 mg/m on days 1 and 8 every 21 days and
      erlotinib 100 mg daily). Arms B and C were considered investigational; the
      primary objective was 6-month progression-free survival. RESULTS: Between March
      2006 and May 2010, 146 eligible patients received protocol therapy. The majority
      of the patients (82%) had stage IV disease, 64% reported adenocarcinoma
      histology, 90% reported current or previous tobacco use, and 28% had a
      performance status of 2. The 6-month progression-free survival rate observed in
      arms A, B, and C was 22% (95% confidence interval [CI] 11-35), 24% (95% CI 13
      36), and 25% (95% CI 15-38), respectively; the median overall survival observed
      was 6.8 months (95% CI 4.8-8.5), 5.8 months (95% CI 3.0-8.3), and 5.6 months (95%
      CI 3.5-8.4), respectively. The rate of grade >=3 hematological and
      nonhematological toxicity observed was similar in all three arms. The best
      overall health-related quality of life response did not differ between treatment
      arms. CONCLUSIONS: Erlotinib or erlotinib and gemcitabine do not warrant further
      investigation in an unselected elderly patient population.

PMID- 21716147
TI  - Significance of thymidylate synthase and thyroid transcription factor 1
      expression in patients with nonsquamous non-small cell lung cancer treated with
      pemetrexed-based chemotherapy.
AB  - INTRODUCTION: This study is to evaluate whether thymidylate synthase (TS) or
      thyroid transcription factor 1 (TTF1) protein expression can predict clinical
      outcomes for pemetrexed-based chemotherapy in patients with nonsquamous non-small
      cell lung cancer (NSCLC). METHODS: Two hundred eighty-five consecutive patients
      with nonsquamous NSCLC treated with pemetrexed-based chemotherapy were
      immunohistochemically analyzed for the expressions of TS and TTF1. RESULTS: TS
      and TTF1 expression were successfully analyzed in 193 and 284 cases,
      respectively. Tumors with TS-negativity or TTF1-positivity were more frequent in
      patients who were female, younger, had adenocarcinoma, or had never smoked.
      Higher response rates for pemetrexed-based chemotherapy were associated with TS
      negativity (33.7% versus 14.1%, p = 0.002) and TTF1-positivity (28.1% versus
      9.8%, p < 0.001). In univariate analysis, progression-free survival for
      pemetrexed-based chemotherapy was significantly longer in groups with
      adenocarcinoma (2.9 versus 1.4 months, p = 0.001), TS-negativity (4.1 versus 2.0
      months, p = 0.001), and TTF1-positivity (3.8 versus 1.3 months, p < 0.001). In
      multivariate analysis, TS-negativity (hazard ratio [HR] = 0.70; 95% confidence
      interval [CI], 0.51-0.97) and TTF1-positivity (HR = 0.51; 95% CI, 0.35-0.73) were
      associated with longer progression-free survival. Patients with TTF1-positive
      tumors also had significantly longer overall survival times than patients with
      TTF1-negative tumors (25.4 versus 14.2 months, HR = 0.55; 95% CI, 0.39-0.77).
      CONCLUSIONS: Low TS or high TTF1 protein expression was significantly associated
      with better clinical outcomes in nonsquamous NSCLC patients who were treated with
      pemetrexed-based chemotherapy. The predictive role of TS or TTF1 expression
      should be further validated in a prospective randomized study.

PMID- 21716148
TI  - Physical activity and concordance between objective and perceived walkability.
AB  - PURPOSE: The study's purpose was to investigate concordance between objective and
      perceived neighborhood walkability, their associations with self-reported walking
      and objective physical activity, and sociodemographic characteristics of
      individuals in neighborhoods with objectively assessed high walkability who
      misperceive it as low. METHODS: In 1925 individuals age 20-66 yr of both high and
      low neighborhood walkability recruited from administrative areas in the city of
      Stockholm, Sweden, objective neighborhood walkability was assessed within a 1000
      m radius of each individual's residential address using geographic information
      systems. Perceived walkability was based on the Neighborhood Environment
      Walkability Scale. Walking was assessed using the International Physical Activity
      Questionnaire, and total physical activity and moderate-to-vigorous physical
      activity (MVPA) were assessed by an accelerometer (ActiGraph). Sociodemographic
      characteristics were self-reported. RESULTS: Objective and perceived neighborhood
      walkability agreed in 67.0% of the individuals, with kappa = 0.34 (95% confidence
      interval (CI) = 0.30-0.38). One-third of the individuals in neighborhoods with
      objectively assessed high walkability misperceived it as low. This nonconcordance
      was more common among older and married/cohabiting individuals. After adjustment
      for sociodemographic characteristics, high objective neighborhood walkability was
      associated with 35.0 (95% CI = 14.6-64.6) and 10.5 (95% CI = -5.2 to 28.5) more
      minutes per week of walking for transportation and leisure, respectively, and 2.8
      (95% CI = 0.9-5.0) more minutes per day of MVPA. High perceived neighborhood
      walkability was associated with 41.5 (95% CI = 15.8-62.9) and 21.8 (95% CI = 2.8
      40.0) more minutes per week of walking for transportation and leisure,
      respectively, and 1.7 (95% CI = -0.3 to 3.7) more minutes per day of MVPA.
      CONCLUSIONS: Objective and perceived neighborhood walkability both contribute to
      the amount of walking and objective physical activity. Both measures of
      neighborhood walkability may be important factors to target in interventions
      aiming at increasing physical activity.

PMID- 21716149
TI  - Different timing of changes in mitochondrial functions following endurance
      training.
AB  - PURPOSE: The objective of this study was to investigate the time course of the
      endurance training-induced adaptations in two major mitochondrial functions.
      METHODS: Forty rats were divided into four groups: a control group and three
      training groups--a 1-d training group, a 5-d training group, and a 10-d training
      group. The training protocol consisted of 30 min of running on a motorized
      treadmill (26 m.min(-1), 15% grade). Nuclear respiratory factor-1; transcription
      factor A, mitochondrial; superoxide dismutase-2; glutathione peroxidase-4; and
      citrate synthase (CS) messenger RNA levels were measured by qPCR. Mitochondrial
      respiration and H2O2 release were assessed using permeabilized fibers of white
      gastrocnemius in situ. Calculation of free radical leak was performed in two
      conditions where substrates were identical in both measurements. CS activity was
      assessed spectrophotometrically. RESULTS: An early time-dependent modulation in
      messenger RNA levels was observed with training: nuclear respiratory factor-1 and
      superoxide dismutase-2 levels increased after acute exercise, transcription
      factor A, mitochondrial and CS levels improved after 5 d, and glutathione
      peroxidase-4 levels increased after 10 d. CS activity improved by 29% +/- 8% (P <
      0.01) after 5 d together with a 50% +/- 7% reduction in the free radical leak (P
      < 0.05). Finally, 10 d of endurance training did not significantly alter
      mitochondrial H2O2 release but increased mitochondrial respiration rates in situ
      (P < 0.05). CONCLUSIONS: Our results demonstrate that mitochondrial adaptations
      follow a sequential program in which mitochondrial respiration and free radical
      leak adaptations occur according to a different timing. Collectively, these
      results suggest early mitochondrial qualitative adaptations in response to
      endurance training.

PMID- 21716150
TI  - Gender differences in head impacts sustained by collegiate ice hockey players.
AB  - PURPOSE: This study aimed to quantify the frequency, magnitude, and location of
      head impacts sustained by male and female collegiate ice hockey players during
      two seasons of play. METHODS: During two seasons, 88 collegiate athletes (51
      females, 37 males) on two female and male National Collegiate Athletic
      Association varsity ice hockey teams wore instrumented helmets. Each helmet was
      equipped with six single-axis accelerometers and a miniature data acquisition
      system to capture and record head impacts sustained during play. Data collected
      from the helmets were postprocessed to compute linear and rotational
      accelerations of the head as well as impact location. The head impact exposure
      data (frequency, location, and magnitude) were then compared between genders.
      RESULTS: Female hockey players experienced a significantly lower (P < 0.001)
      number of impacts per athlete exposure than males (females = 1.7 +/- 0.7, males =
      2.9 +/- 1.2). The frequency of impacts by location was the same between genders
      (P > 0.278) for all locations except the right side of the head, where males
      received fewer impacts than females (P = 0.031). Female hockey players were 1.1
      times more likely than males to sustain an impact less than 50 g, whereas males
      were 1.3 times more likely to sustain an impact greater than 100 g. Similarly,
      males were 1.9 times more likely to sustain an impact with peak rotational
      acceleration greater than 5000 rad.s(-2) and 3.5 times more likely to sustain an
      impact greater than 10,000 rad.s(-2). CONCLUSIONS: Although the incidence of
      concussion has typically been higher for female hockey players than male hockey
      players, female players sustain fewer impacts and impacts resulting in lower head
      acceleration than males. Further study is required to better understand the
      intrinsic and extrinsic risk factors that lead to higher rates of concussion for
      females that have been previously reported.

PMID- 21716151
TI  - Cold water immersion recovery after simulated collision sport exercise.
AB  - PURPOSE: This investigation examined the effects of cold water immersion (CWI)
      recovery after simulated collision sport exercise. METHODS: Ten male rugby
      athletes performed three sessions consisting of a 2 * 30-min intermittent-sprint
      exercise (ISE) protocol with either tackling (T) or no tackling (CONT), followed
      by a 20-min CWI intervention (TCWI) or passive recovery (TPASS and CONT) in a
      randomized order. The ISE consisted of a 15-m sprint every minute separated by
      self-paced bouts of hard running, jogging, and walking for the remainder of the
      minute. Every sixth rotation, participants performed 5 * 10-m runs, receiving a
      shoulder-led tackle to the lower body on each effort. Sprint time and distance
      covered during ISE were recorded, with voluntary (maximal voluntary contraction;
      MVC) and evoked neuromuscular function (voluntary activation; VA), electromyogram
      (root mean square (RMS)), ratings of perceived muscle soreness (MS), capillary
      and venous blood markers for metabolites and muscle damage, respectively measured
      before and after exercise, immediately after recovery, and 2 and 24 h after
      recovery. RESULTS: Total distance covered during exercise was significantly
      greater in CONT (P = 0.01), without differences between TPASS and TCWI (P >
      0.05). TCWI resulted in increased MVC, VA, and RMS immediately after recovery (P
      < 0.05). M-wave amplitude and peak twitch were significantly increased after
      recovery and 2 h after recovery, respectively, in TCWI (P < 0.05). Although TCWI
      had no effect on the elevation in blood markers for muscle damage (P > 0.05),
      lactate was significantly reduced after recovery compared with TPASS (P = 0.04).
      CWI also resulted in reduced MS 2 h after recovery compared with TPASS (P <
      0.05). CONCLUSIONS: The introduction of body contact reduces exercise
      performance, whereas the use of CWI results in a faster recovery of MVC, VA, and
      RMS and improves muscle contractile properties and perceptions of soreness after
      collision-based exercise.

PMID- 21716152
TI  - Lowering physical activity impairs glycemic control in healthy volunteers.
AB  - INTRODUCTION: Postprandial glucose (PPG) is an independent predictor of
      cardiovascular events and death, regardless of diabetes status. Whereas changes
      in physical activity produce changes in insulin sensitivity, it is not clear
      whether changes in daily physical activity directly affect PPG in healthy free
      living persons. METHODS: We used continuous glucose monitors to measure PPG and
      PPG excursions (DeltaPPG, postmeal - premeal blood glucose) at 30-min increments
      after meals in healthy habitually active volunteers (n = 12, age = 29 +/- 1 yr,
      body mass index = 23.6 +/- 0.9 kg.m(-2), VO2max = 53.6 +/- 3.0 mL.kg(-1).min(-1))
      during 3 d of habitual (>=10,000 steps per day) and reduced (<5000 steps per day)
      physical activity. Diets were standardized across monitoring periods, and fasting
      state oral glucose tolerance tests (OGTT) were performed on the fourth day of
      each monitoring period. RESULTS: During 3 d of reduced physical activity (12,956
      +/- 769 to 4319 +/- 256 steps per day), PPG increased at 30 and 60 min after a
      meal (6.31 +/- 0.19 to 6.68 +/- 0.23 mmol.L(-1) and 5.75 +/- 0.16 to 6.26 +/-
      0.28 mmol.L(-1), P < 0.05 relative to corresponding active time point), and
      DeltaPPG increased by 42%, 97%, and 33% at 30, 60, and 90 min after a meal,
      respectively (P < 0.05). Insulin and C-peptide responses to the OGTT increased
      after 3 d of reduced activity (P < 0.05), and the glucose response to the OGTT
      did not change significantly. CONCLUSIONS: Thus, despite evidence of compensatory
      increases in plasma insulin during an OGTT, DeltaPPG assessed by continuous
      glucose monitoring systems increased markedly during 3 d of reduced physical
      activity in otherwise healthy free-living individuals. These data indicate that
      daily physical activity is an important mediator of glycemic control, even among
      healthy individuals, and reinforce the utility of physical activity in preventing
      pathologies associated with elevated PPG.

PMID- 21716153
TI  - Cystine glutamate exchanger upregulation by retinoic acid induces neuroprotection
      in neural stem cells.
AB  - Oxidative stress and excitotoxic injury are commonly associated with several
      neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and
      periventricular leukomalacia. As cystine is imported into the cell, it is used in
      the synthesis of intracellular glutathione, an important antioxidant necessary
      for the defense of brain cells from oxidative stress and glutamate-mediated
      excitotoxicity. Recent studies have shown that retinoic acid increases the
      activity of glutathione synthesis and exhibits neuroprotective properties in
      brain cells. Previously, we have shown that the regulation of the cystine
      glutamate exchanger (system Xc(-)) also leads to neuroprotection. Here, we
      examined the effects of retinoic acid on the regulation of system Xc(-). Our
      results suggest that retinoic acid-induced neuroprotection is mediated through
      system Xc(-) by regulating glutathione biosynthesis.

PMID- 21716154
TI  - Neuromodulation in epilepsy.
AB  - Neuromodulation strategies have been proposed to treat a variety of neurological
      disorders, including medication-resistant epilepsy. Electrical stimulation of
      both central and peripheral nervous systems has emerged as a possible alternative
      for patients who are not deemed to be good candidates for resective procedures.
      In addition to well-established treatments such as vagus nerve stimulation,
      epilepsy centers around the world are investigating the safety and efficacy of
      neurostimulation at different brain targets, including the hippocampus, thalamus,
      and subthalamic nucleus. Also promising are the preliminary results of responsive
      neuromodulation studies, which involve the delivery of stimulation to the brain
      in response to detected epileptiform or preepileptiform activity. In addition to
      electrical stimulation, novel therapeutic methods that may open new horizons in
      the management of epilepsy include transcranial magnetic stimulation, focal drug
      delivery, cellular transplantation, and gene therapy. We review the current
      strategies and future applications of neuromodulation in epilepsy.

PMID- 21716155
TI  - Outcome predictors of gamma knife radiosurgery for renal cell carcinoma
      metastases.
AB  - BACKGROUND: Although whole-brain radiation therapy (WBRT) has been a standard
      palliative management for brain metastases from renal cell carcinoma, its benefit
      has been elusive because of radiobiological resistance. OBJECTIVE: To evaluate
      the role of stereotactic radiosurgery (SRS) in the management of brain metastases
      from renal cell carcinoma. METHODS: We reviewed records from 158 consecutive
      patients (men = 111, women = 47) who underwent SRS for 531 brain metastases from
      renal cell carcinoma. The median patient age was 61 years (range, 38-83 years),
      and the median number of tumors per patient was 1 (range, 1-10). Seventy-nine
      patients (50%) had solitary brain metastasis. Fifty-seven patients (36%)
      underwent prior WBRT. The median total tumor volume for each patient was 3.0 cm3
      (range, 0.09-47 cm). RESULTS: The overall survival after SRS was 60%, 38%, and
      19% at 6, 12, and 24 months, respectively, with a median survival of 8.2 months.
      Factors associated with longer survival included younger age, longer interval
      between primary diagnosis and brain metastases, lower recursive partitioning
      analysis class, higher Karnofsky performance status, smaller number of brain
      metastases, and no prior WBRT. Median survival for patients with < 2 brain
      metastases, higher Karnofsky performance status (> 90), and no prior WBRT was 12
      months after SRS. Sustained local tumor control was achieved in 92% of patients.
      Symptomatic adverse radiation effects occurred in 7%. Overall, 70% of patients
      improved or remained neurologically stable. CONCLUSION: Stereotactic radiosurgery
      is an especially valuable option for patients with higher Karnofsky performance
      status and smaller number of brain metastases from renal cell carcinoma.

PMID- 21716156
TI  - The changing role of liver biopsy in diagnosis and management of
      haemochromatosis.
AB  - Liver biopsy with histological examination of liver tissue was for many years the
      cornerstone of the diagnosis of haemochromatosis, allowing assessment of the
      degree of iron overload and examination of liver histology for the acute and
      chronic effects of iron overload. In the past two decades the role of liver
      biopsy in haemochromatosis has changed dramatically. Liver biopsy is rarely
      requested for two main reasons: (1) genetic testing for human haemochromatosis
      (HFE) mutations has proved to be very reliable in the diagnosis of
      haemochromatosis in Caucasian populations, and (2) the majority of patients with
      haemochromatosis are now diagnosed at an early stage well before permanent tissue
      damage occurs, so the need to assess tissue and organ damage has diminished.
      Liver biopsy continues to have a very important role in a small number of
      haemochromatosis patients for whom it has both diagnostic and prognostic
      implications. Liver biopsy is essential for the accurate assessment of patients
      with non-HFE haemochromatosis and in patients who have dual pathology. It is also
      useful where there appears to be a discrepancy between HFE genotypes and iron
      studies, particularly in HFE heterozygotes. Finally, liver biopsy is currently
      the 'gold standard' for the diagnosis of fibrosis and cirrhosis, although this is
      changing as non-invasive methods for assessing fibrosis become more reliable and
      available. Therefore, it is important that pathologists maintain their knowledge
      and skills in the use of liver biopsy in haemochromatosis and other iron storage
      disorders.

PMID- 21716157
TI  - Morphological subtypes of ovarian carcinoma: a review with emphasis on new
      developments and pathogenesis.
AB  - Ovarian carcinomas comprise a heterogeneous group of neoplasms, the four most
      common subtypes being serous, endometrioid, clear cell and mucinous. In recent
      years, our understanding of the underlying pathogenesis and initiating molecular
      events in the different tumour subtypes has greatly increased, and although
      ovarian carcinoma is often considered clinically as one disease, there is now a
      much greater realisation that the various subtypes have a different natural
      behaviour and prognosis. At present, adjuvant therapy is mainly dependent upon
      tumour stage and grade rather than type; however, this is likely to change in the
      future with the development of new chemotherapeutic agents and targeted therapies
      and clinical trials are necessary to evaluate the efficacy of different agents in
      clear cell, mucinous and low grade serous carcinomas, neoplasms which are
      considered relatively resistant to traditional chemotherapeutic regimes. In this
      review, the major subtypes of ovarian carcinoma are discussed. It is now firmly
      established that there are two distinct types of ovarian serous carcinoma, low
      grade and high grade, the former being much less common and arising in many cases
      from a serous borderline tumour. Low grade and high grade serous carcinoma
      represent two distinct tumour types with a different underlying pathogenesis
      rather than low grade and high grade variants of the same neoplasm. Both are
      usually advanced stage (stage III or IV) at diagnosis. B-raf and k-ras mutations
      are important molecular events in low grade serous carcinomas while high grade
      serous carcinomas are almost always associated with TP53 mutation. There is now
      emerging and compelling evidence that many high grade serous carcinomas (by far
      the most common subtype of ovarian carcinoma) actually arise from the epithelium
      of the distal fallopian tube. Future studies regarding the initiating molecular
      events in the development of this aggressive neoplasm should concentrate on this
      site. Primary ovarian mucinous carcinomas are uncommon, almost always unilateral
      and stage I, and largely of so-called intestinal or enteric type. Most arise in a
      stepwise manner from a pre-existing mucinous cystadenoma and mucinous borderline
      tumour. Endometrioid and clear cell carcinomas typically present as low stage
      neoplasms and in many, or most, cases arise from endometriosis; the former are
      usually well differentiated and there is now evidence that the majority of
      neoplasms reported in the past as high grade endometrioid carcinoma are of serous
      type. WT1 is useful in this regard since it is a relatively specific marker of a
      serous phenotype. It is recommended that different subtypes of ovarian carcinoma
      are graded using different systems rather than employing a universal grading
      system.

PMID- 21716158
TI  - Clostridium difficile laboratory testing in Australia and New Zealand: national
      survey results and Australasian Society for Infectious Diseases recommendations
      for best practice.
AB  - AIMS: In order to improve the future reliability of surveillance for Clostridium
      difficile infection (CDI), an Australia/New Zealand-wide survey was conducted to
      examine methods of laboratory diagnosis in use, identify deficiencies in practice
      and burden of CDI. METHODS: An online survey of 48 Australian and New Zealand
      microbiology laboratories (private and public) was conducted in late 2009 and
      2010 to collect information about methods of detection in use and collective
      testing experience from July 2008 to June 2009. RESULTS: The overall prevalence
      (proportion positive of all faecal specimens tested) of C. difficile in 123,574
      tested samples was 5.3%. The incidence rate across jurisdictions varied between
      18.0 per 100,000 population in Victoria to 35.8 per 100,000 population in
      Tasmania, with a mean for Australia of 25.6 per 100,000 population. The incidence
      rate in New Zealand was 21.5 per 100,000 population. Most laboratories (60%)
      screened stools with an enzyme immunoassay (EIA) or equivalent that detected both
      toxins A and B. CONCLUSIONS: The low overall rates reported here may reflect the
      lack of sensitivity of diagnostic testing procedures currently used in Australia
      and New Zealand to detect C. difficile. Recommendations for best practice in
      diagnosis of C. difficile were developed by the Australasian Society for
      Infectious Diseases (ASID) C. difficile working party and later endorsed by ASID.

PMID- 21716159
TI  - Prognostic factors in prostate cancer. Key elements in structured histopathology
      reporting of radical prostatectomy specimens.
AB  - Prostate cancer is the most common visceral cancer and the second most common
      cause of cancer death in males. The number of radical prostatectomies performed
      each year is increasing and accurate data from the histopathological examination
      of these specimens aid clinicians in stratifying patients for surveillance and
      adjuvant therapies. This review focuses on the histopathological prognostic
      factors which should be routinely recorded in pathology reports and complements
      the Royal College of Pathologists of Australasia Structured Reporting Protocol
      for Prostate Cancer (Radical Prostatectomy). Such structured pathology reports
      have been shown to significantly enhance the completeness and quality of data
      provided to clinicians. The review also discusses the International Society for
      Urological Pathology Consensus Conference recommendations which were published
      recently.

PMID- 21716160
TI  - Diagnostic performance of serum cobalamin tests: a systematic review and meta
      analysis.
AB  - AIMS: Serum cobalamin (cbl, vitamin B(12)) tests are routinely ordered for
      investigating conditions potentially amenable to cbl supplementation. This study
      aimed to systematically assess the evidence of diagnostic accuracy for serum cbl
      tests across patient subgroups. METHODS: Seven medical databases were searched
      (1990 to November 2009). Studies were included that compared serum cbl to a
      reference standard (all reference standards employed). Study quality was assessed
      using QUADAS. Summary estimates of test performance were determined using the
      bivariate model and hierarchical summary receiver operating characteristic curves
      (HSROC). RESULTS: Of 2878 identified studies, 54 were included. Studies rated
      poorly against QUADAS criteria. Positive (PLR) and negative likelihood ratios
      (NLR) were 2.72 [95% confidence interval (CI) 1.95, 3.81] and 0.59 (0.49, 0.72),
      respectively (studies employing methylmalonic acid as the referent). In studies
      employing a clinical reference standard, PLR was 3.33 (0.92, 12.10) and NLR 0.34
      (0.13, 0.89). Test performance did not vary by clinical indication, test method
      or age. CONCLUSION: This review was limited by the quality of the evidence base
      and lack of a gold standard. From the available evidence, diagnosis of conditions
      amenable to cbl supplementation on the basis of serum cbl level alone cannot be
      considered a reliable approach to investigating suspected vitamin deficiency.

PMID- 21716161
TI  - BRAF, p53 and SOX2 in anaplastic thyroid carcinoma: evidence for multistep
      carcinogenesis.
AB  - AIMS: The aim of this study was to genotype a series of papillary thyroid
      carcinomas (PTCs) and anaplastic thyroid carcinomas (ATCs) for BRAF mutation, and
      to evaluate p53 and SOX2 expression as factors implicated in tumour progression.
      METHODS: The study included 17 PTCs and 14 ATCs. Analysis of the exon 15 of BRAF
      was based on direct sequencing. Immunohistochemistry was used to evaluate p53 and
      SOX2 expression. RESULTS: V600E (c.1799T>A) mutation was observed in 53% (9/17)
      of PTCs. Two cases of ATCs (2/14; 14%), both with PTC component, harboured BRAF
      mutation: the classical V600E mutation and an undocumented duplication of codon
      599 (c.1795_1797dup; p.Thr599dup). These mutations were present in ATC as well as
      PTC tumour cells. Overexpression of p53 and SOX2 was depicted respectively in 64%
      (9/14) and 29% (4/14) of ATCs, and absent in PTCs. CONCLUSION: We confirm that
      V600E mutation is a frequent and specific event in PTC. BRAF-mutated ATCs are
      associated with a PTC component displaying the same mutation. We describe a new
      mutation of BRAF, T599dup, in a case of ATC with tall cell PTC component.
      Moreover, progression from PTC to ATC could be favoured by further TP53 mutation
      and SOX2 expression.

PMID- 21716162
TI  - Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate
      cancer.
AB  - BACKGROUND: To explore associations with prostate cancer and farming, it is
      important to investigate the relationship between pesticide use and single
      nucleotide polymorphisms (SNPs) in xenobiotic metabolic enzyme (XME) genes.
      OBJECTIVE: [corrected] We evaluated pesticide-SNP interactions between 45
      pesticides and 1913 XME SNPs with respect to prostrate cancer among 776 cases and
      1444 controls in the Agricultural Health Study. METHODS: We used unconditional
      logistic regression to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs). Multiplicative SNP-pesticide interactions were calculated using a
      likelihood ratio test. RESULTS: A positive monotonic interaction was observed
      between petroleum oil/petroleum distillate use and rs1883633 in the oxidative
      stress gene glutamate cysteine ligase (GCLC; P interaction=1.0*10(-4)); men
      carrying at least one variant allele (minor allele) experienced an increased
      prostate cancer risk (OR=3.7, 95% CI: 1.9-7.3). Among men carrying the variant
      allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide
      hydrolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, an increased
      prostate cancer risk was observed with high, compared with no, petroleum
      oil/petroleum distillate (OR=1.9, 95% CI: 1.1-3.2, P interaction=0.01; OR=2.1,
      95% CI: 1.1-4.0, P interaction=0.01), or terbufos (OR=3.0, 95% CI: 1.5-6.0, P
      interaction=2.0*10(-3)) use, respectively. No interactions were deemed noteworthy
      at the false discovery rate=0.20 level; the number of observed interactions in
      XMEs was comparable with the number expected by chance alone. CONCLUSION: We
      observed several pesticide-SNP interactions in oxidative stress and phase I/II
      enzyme genes and risk of prostate cancer. Additional work is needed to explain
      the joint contribution of genetic variation in XMEs, pesticide use, and prostate
      cancer risk.

PMID- 21716163
TI  - Association of HLA-DRB1 alleles and neuropsychological function in autism.
AB  - Evidence suggests an association between autism and immune dysfunction. The
      associations between human lymphocyte antigen (HLA)-A2, B44, DRbeta1*04 (DR4),
      C4B, and haplotype B44-SC30-DR4 and autism have been reported in western
      countries but there is a lack of such information in Asian population. This study
      aimed to assess the association between HLA-DRB1 allele frequencies and the
      clinical phenomenology of autism. The sample included 141 participants (male,
      87.2%), who were diagnosed with autistic disorder based on clinical assessments
      and structured interviews using the Chinese version of the Autism Diagnostic
      Interview-Revised, and 156 healthy controls (male, 38.6%). The HLA-DRB1 alleles
      were determined by sequencing-based typing method. A subsample of patients (n=39)
      were assessed for intelligence and neuropsychological functions. The results
      showed that the pattern of DRB1 allele frequencies was significantly different
      between patients with autism and the controls (P=0.047). After adjusting for sex
      by haplotype regression, the frequencies of DR4, DR11, and DR14 were
      significantly different between patients with autism and healthy controls. In
      addition, patients with autism and DR4, DR11, or DR14 had different performance
      on intelligence and neuropsychology tests. Despite a relatively small sample size
      and a case-control association design, the findings suggest HLA-DRB1 gene might
      be associated with autism in Han Chinese. The true functional variants associated
      with autism in our samples remain to be further clarified. It warrants a
      replication study of a larger family sample and to validate the HLA genetic
      association with autism and its influence on neuropsychological function.

PMID- 21716164
TI  - Relationship between retinal nerve fiber layer and visual field function in human
      immunodeficiency virus-infected patients without retinitis.
AB  - PURPOSE: To evaluate the spatial association between visual field (VF)
      sensitivity loss and retinal nerve fiber layer (RNFL) thinning in patients
      infected by the human immunodeficiency virus. METHODS: Fifty-one eyes of 51 human
      immunodeficiency virus-infected patients and 22 eyes of 22 control subjects were
      enrolled. Patients were evaluated using the Fast RNFL scan strategy on Stratus
      OCT and the 24-2 full-threshold program on the Humphrey Matrix frequency doubling
      technology (FDT) perimeter. Associations between RNFL thickness and VF
      sensitivity were evaluated globally, in 12 clock-hour optical coherence
      tomography sectors and in 21 VF zones; linear and quadratic regression models
      were used in the statistical analysis. RESULTS: The linear and quadratic
      regression associations between the FDT Matrix pattern standard deviation and the
      average RNFL thickness in human immunodeficiency virus-infected patients were r2
      = 0.185 and r2 = 0.218 (P < 0.05), respectively. The correlation between the FDT
      Matrix mean deviation and the average RNFL thickness was not significant (P >
      0.05). Stronger associations were found when regional RNFL thinning was compared
      with locally measured FDT Matrix pattern deviation, especially between nasal RNFL
      measurements and temporal VF zones, and between superior RNFL measurements and
      inferior VF zones. CONCLUSION: Retinal nerve fiber layer thinning was related to
      VF sensitivity loss in human immunodeficiency virus-infected patients and
      regional associations between optical coherence tomography and FDT Matrix sectors
      were stronger than the associations between global measurements.

PMID- 21716165
TI  - Bilateral effect of unilateral ranibizumab in patients with uveitis-related
      macular edema.
AB  - PURPOSE: To describe an observed therapeutic effect of ranibizumab in untreated
      contralateral eyes of patients with bilateral uveitis-related cystoid macular
      edema. METHODS: The authors conducted an open-label, prospective, nonrandomized,
      interventional study to evaluate the effect of intravitreal ranibizumab
      injections for the off-label treatment of persistent uveitic cystoid macular
      edema. Patients were given 3 monthly injections of 0.5 mg intravitreal
      ranibizumab in the eye with worse vision. Subsequent monthly ranibizumab
      injections were administered based on macular thickness measurements. Best
      spectacle corrected visual acuity measurements and optical coherence tomography
      scans were performed on both eyes at baseline and at monthly follow-up visits.
      RESULTS: Three of the seven patients in our nonrandomized consecutive case series
      presented with controlled uveitis and cystoid macular edema bilaterally. Two of
      the three patients demonstrated a significant improvement in visual acuity and a
      reduction in macular edema in both eyes after three monthly injections to the
      study eye. One patient experienced limited effect bilaterally possibly because of
      the presence of epiretinal membranes in both eyes. CONCLUSION: The authors
      observed a beneficial effect of ranibizumab in both eyes of patients who were
      treated unilaterally for uveitis-related cystoid macular edema. This warrants
      further investigation of the pharmacokinetics and systemic availability of
      ranibizumab, particularly in patients with uveitis.

PMID- 21716166
TI  - Case-control study of risk factors for no light perception after open-globe
      injury: eye injury vitrectomy study.
AB  - PURPOSE: Investigate possible risk factors of no light perception (NLP) after
      open-globe injury. Explore whether these risk factors are predictors for an
      unfavorable visual outcome. METHODS: This case-control study matched 72 eyes with
      NLP according to type and zone of injury to 2 controls per case with light
      perception or better vision. Cases were selected from the Eye Injury Vitrectomy
      Study database. All injured eyes in the study underwent surgical intervention.
      RESULTS: Ciliary body damage (odds ratio = 2.94), closed funnel retinal
      detachment (odds ratio = 2.43), and choroidal damage (odds ratio = 2.80) were
      independent risk factors for NLP after open-globe injury. There were 67
      traumatized eyes with NLP that had >=1 of these risk factors. In 43 of the cases
      (64.2%), the eyes recovered light perception or better after vitreoretinal
      surgery. The five traumatized NLP cases without these risk factors obtained a
      favorable visual outcome after vitreoretinal surgery. There was no statistical
      significance in visual outcome between them (P = 0.162). CONCLUSION: Ciliary body
      damage, closed funnel retinal detachment, and choroidal damage are independent
      risk factors for NLP posttrauma but not prognostic indicators for NLP visual
      outcome. Traumatized eyes with NLP may recover light perception or better vision
      if appropriate interventional measures are used for treatment of the injured
      ciliary body, retina, and choroid.

PMID- 21716167
TI  - Morphologic characteristics of retinal arterial macroaneurysm and its regression
      pattern on spectral-domain optical coherence tomography.
AB  - PURPOSE: To investigate morphologic characteristics of retinal arterial
      macroaneurysm (RAM) and its regression pattern using spectral-domain optical
      coherence tomography. METHODS: This observational case series included six eyes
      of six patients with RAM. All patients had undergone repeated comprehensive
      ophthalmologic examination, including measurement of best-corrected visual
      acuity, slit-lamp biomicroscopy, indirect fundus examination, fundus photography,
      fluorescein angiography, and spectral-domain optical coherence tomography
      (Spectralis OCT). Morphologic findings of RAM on spectral-domain optical
      coherence tomography and changes after treatment were investigated. RESULTS: On
      initial diagnosis, eyes with RAMs showed a round hyperreflective wall with a
      hyporeflective lumen on spectral-domain optical coherence tomography. Five of six
      patients underwent direct laser photocoagulation to the RAM. One hour after
      treatment, the lumen of the RAM showed a homogeneous high reflectance, indicating
      occlusion with thrombus. One or 2 months after treatment, spectral-domain optical
      coherence tomography demonstrated almost entirely obliterated RAMs and decreased
      perianeurysmal retinal edema. One patient showed spontaneous rupture and
      involution of RAM. Superficial location of RAM was associated with hemorrhagic
      complications. CONCLUSION: Spectral-domain optical coherence tomography can show
      morphologic characteristics of RAM and structural changes after treatment. These
      new findings can be valuable not only in clinical diagnosis but also in
      predicting the treatment response of RAM.

PMID- 21716168
TI  - Blood clump-assisted vitrectomy and internal limiting membrane peeling for
      macular hole repair.
AB  - PURPOSE: To evaluate the efficacy and safety of using diluted autologous blood
      clumps to assist in vitrectomy and internal limiting membrane (ILM) peeling for
      macular hole (MH) repair. METHODS: Twenty-six patients with MHs who underwent ILM
      peeling were enrolled. The blood clump solution was prepared by mixing autologous
      whole blood with 5% glucose water. This solution was introduced to identify the
      posterior vitreous and was then used to coat the surface of the ILM in the
      macular area. The blood clump-coated ILM was removed with forceps in a circular
      fashion. The MH closure rate, the pre- and postoperative best-corrected visual
      acuity change, and retinal changes were evaluated. RESULTS: The blood clump
      assisted procedure effectively labeled the posterior vitreous and coated the ILM,
      enhancing the visibility of ILM and, thus, facilitating MH repair. The MHs were
      closed by a single surgery in 24 eyes (92%), and the other 2 holes were closed
      after a second gas-fluid exchange. The pre- and postoperative mean best-corrected
      visual acuities were 0.96 +/- 0.3 and 0.38 +/- 0.3 (logarithm of the minimum
      angle of resolution visual acuity +/- SD, P < 0.001), respectively. No toxic
      fundus changes were observed during the follow-up period. CONCLUSION: This novel
      blood clump-assisted procedure effectively labeled the posterior vitreous and
      coated the ILM, enhancing the visibility of ILM and thereby facilitating MH
      repair.

PMID- 21716169
TI  - Proteomics--a blessing or a curse? Application of proteomics technology to
      transplant medicine.
AB  - Proteomics has emerged as a powerful tool in clinical biomarker research. In the
      field of transplantation, proteomics aims not only at developing noninvasive
      tools for immune monitoring and identifying biomarkers of allograft rejection but
      also to gain mechanistic insights into the pathophysiology of an alloimmune
      response and hence defining new therapeutic targets. A basic knowledge of
      proteomic technology is a prerequisite to appreciate the complex data generated
      and required for critical evaluation/interpretation of proteomic-driven studies.
      This review provides an overview of proteomic approaches and its underlying
      concepts and discusses the advantages, clinical implications, challenges, and
      limitations of this exciting modality in transplantation.

PMID- 21716170
TI  - Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant
      recipients.
AB  - BACKGROUND: Obliterative bronchiolitis poses a primary obstacle for long-term
      survival of lung transplant recipients and manifests clinically as bronchiolitis
      obliterans syndrome (BOS). Establishing a molecular level screening method to
      detect BOS-related proteome changes before its diagnosis by forced expiratory
      volume surrogate marker criteria was the main objective of this study. METHODS:
      Bronchoalveolar lavage was performed in 82 lung transplant recipients (48/34
      with/without known BOS development) at different time points between 12 and 48
      months after lung transplantation. A mass spectrometry-based method was devised
      to generate bronchoalveolar lavage fluid proteome profiles that were screened for
      BOS-specific alterations. Statistically significant marker peptides and proteins
      were identified and validated by in-gel digestion, tandem mass spectrometric
      sequencing, and quantitative immunoassays. RESULTS: Among the panel of
      statistically significant markers were Clara cell protein, calgranulin A, human
      neutrophil peptides, and the antimicrobial agent histatin. To assess their
      clinical relevance, a highly sensitive and specific classifier model was
      developed. Positive BOS classification by monitoring of seven polypeptides
      correlated strongly with a significant decrease in BOS-free time. Thus, it was
      possible to detect high-risk patients early on in the pathogenetic process.
      CONCLUSIONS: Monitoring the bronchoalveolar lavage fluid levels of seven
      polypeptides detected by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry allows a reliable prediction of early BOS using a Random
      Forest decision tree-based classifier model. The high accuracy of this robust
      model and its synergistic potential in combination with established forced
      expiratory volume-based diagnostics could make it an effective tool to supplement
      the current diagnostic regime after multicentric validation.

PMID- 21716171
TI  - Biliary dilatation and strictures after composite liver-small bowel
      transplantation in children: defining a newly recognized complication.
AB  - BACKGROUND: Biliary dilatation and strictures (BDS) are well recognized after
      liver transplantation but not reported after composite liver-small bowel
      transplantation (CLSBT). We aimed to describe and propose a classification of BDS
      in children undergoing CLSBT and analyze the potential risk factors. METHODS:
      Biliary complications of 47 consecutive children undergoing CLSBT were reviewed
      and classified according to presentation, location, and intervention required.
      The following variables were studied: small recipient (weight, <10 kg), donor
      recipient weight ratio, liver/bowel graft reduction/not, partial/full pancreas,
      liver/bowel rejection, and median cold ischemia time (>454 min). RESULTS: Twenty
      one (45%) children developed BDS at median 190 days (22 [7-138] months follow
      up). Five distinct biliary lesions were identified. Most of the BDS (14/21; 67%)
      consisted of sphincter dysfunction-related bile duct dilatation (type I), whereas
      others (7/21; 33%) comprised extrahepatic bile duct (type II; n=3), hilar (type
      III; n=1), segmental (type IV; n=1), and diffuse (type V; n=2) intrahepatic
      strictures. None of the graft reduction strategies or other variables studied
      demonstrated a significant association with BDS. Therapeutic intervention was
      required in 1 of 14 type I and four of seven type II to V BDS in the form of
      percutaneous biliary dilatation with or without drainage. CONCLUSION: This
      article identifies BDS after CLSBT as a frequent late complication after CLSBT,
      which has a benign outcome in most cases. The natural history of children with
      extrahepatic and intrahepatic strictures is not yet clear and will need
      multicenter prospective studies.

PMID- 21716172
TI  - Absorbable phenylpropenoyl sucroses from Polygala tenuifolia.
AB  - Three phenylpropenoyl sucroses--sibiricose A5, A6 and 3',6-disinapoyl sucrose-
      were isolated from the 30% EtOH extract of Polygala tenuifolia, which displayed
      antidepressant-like action. HPLC analysis indicated that the three
      phenylpropenoyl sucroses could be absorbed into serum. From the serum
      pharmacochemistry point of view, these three phenylpropenoyl sucroses might
      prevent or relieve depression.

PMID- 21716173
TI  - The relationship of nitrogen and C/N ratio with secondary metabolites levels and
      antioxidant activities in three varieties of Malaysian kacip Fatimah (Labisia
      pumila Blume).
AB  - Kacip Fatimah (Labisia pumila Blume), one of the most famous and widely used
      herbs, especially in Southeast Asia, is found to have interesting bioactive
      compounds and displays health promoting properties. In this study, the
      antioxidant activities of the methanol extracts of leaves, stems and roots of
      three varieties of L. pumila (var. alata, pumila and lanceolata) were evaluated
      in an effort to compare and validate the medicinal potential of this indigenous
      Malaysian herb species. The antioxidant activity determined by the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) assay, as well as the total amount of phenolics and
      flavonoids were the highest in the leaves, followed by the stems and roots in all
      the varieties. A similar trend was displayed by the ferric reducing antioxidant
      potential (FRAP) activity, suggesting that the L. pumila varieties possess high
      foliar antioxidant properties. At low FRAP activity concentrations, the values of
      the leaves' inhibition activity in the three varieties were significantly higher
      than those of the stems and roots, with var. alata exhibiting higher antioxidant
      activities and total contents of phenolics and flavonoids compared to the
      varieties pumila and lanceolata. The high production of secondary metabolites and
      antioxidant activities in var. alata were firmly related to low nitrogen content
      and high C/N ratio in plant parts. The study also demonstrated a positive
      correlation between secondary metabolite content and antioxidant activities, and
      revealed that the consumption of L. pumila could exert several beneficial effects
      by virtue of its antioxidant activity.

PMID- 21716174
TI  - Microwave assisted synthesis of novel functionalized hydantoin derivatives and
      their conversion to 5-(Z) arylidene-4H-imidazoles.
AB  - 2-(Alkyl-1-yl)-1H-imidazol-5(4H)-ones 5a-n were synthesized via nucleophilic
      substitution of the methylsulfanyl group of the corresponding 2-(methylthio)-1H
      imidazol-5(4H)-ones 3a-c with suitably substituted secondary amines. The starting
      2-thioxo- imidazolidin-4-ones 2a,2b were prepared by condensation of
      thiohydantoin and benzo[b]-thiophene-3-carbaldehyde or benzofuran-3-carbaldehyde
      under microwave irracdiation (MW) conditions. 2-Methylthio derivatives 3a-c were
      prepared by treatment of 2a-b with methyl iodide in the presence of aqueous
      sodium hydroxide.

PMID- 21716175
TI  - Multivariate optimization in the biosynthesis of a triethanolamine (TEA)-based
      esterquat cationic surfactant using an artificial neural network.
AB  - An Artificial Neural Network (ANN) based on the Quick Propagation (QP) algorithm
      was used in conjunction with an experimental design to optimize the lipase
      catalyzed reaction conditions for the preparation of a triethanolamine (TEA)
      based esterquat cationic surfactant. Using the best performing ANN, the optimum
      conditions predicted were an enzyme amount of 4.77 w/w%, reaction time of 24 h,
      reaction temperature of 61.9  degrees C, substrate (oleic acid: triethanolamine)
      molar ratio of 1:1 mole and agitation speed of 480 r.p.m. The relative deviation
      percentage under these conditions was less than 4%. The optimized method was
      successfully applied to the synthesis of the TEA-based esterquat cationic
      surfactant at a 2,000 mL scale. This method represents a more flexible and
      convenient means for optimizing enzymatic reaction using ANN than has been
      previously reported by conventional methods.

PMID- 21716176
TI  - An electrochemical synthesis of functionalized arylpyrimidines from 4-amino-6
      chloropyrimidines and aryl halides.
AB  - A range of novel 4-amino-6-arylpyrimidines has been prepared under mild
      conditions by an electrochemical reductive cross-coupling between 4-amino-6
      chloro-pyrimidines and functionalized aryl halides. The process, which employs a
      sacrificial iron anode in conjunction with a nickel(II) catalyst, allows the
      formation of coupling products in moderate to high yields.

PMID- 21716177
TI  - Induction of apoptosis in human promyelocytic leukemia HL60 cells by panaxynol
      and panaxydol.
AB  - Panaxynol and panaxydol are naturally occurring polyacetylenes, isolated from the
      lipophilic fractions of Panax notoginseng, that exert anti-proliferative effects
      against malignant cells. However, to the best of our knowledge, no study
      concerning the inhibitory effects of the two polyacetylenes on cell growth of
      human promyelocytic leukemia cells has been reported. In this paper, we examined
      the antiproliferation and proapoptotic effects of panaxynol and panaxydol on HL60
      cells and investigated their mechanism of action. Cell growth inhibition of
      panaxynol and panaxydol were determined by trypan blue dye exclusion assays.
      Apoptosis of cells was revealed by morphological observation, analysis for
      nuclear DNA distribution and by annexin V-FITC/ PI staining using flow cytometry.
      It was found that panaxynol and panaxydol markedly inhibited proliferation of
      HL60 cells in a time- and dose-dependent manner via an apoptotic pathway. In
      concern with these findings, Western blot analysis showed proteolytic activation
      of PKCdelta, caspase-3 activation and cleavage of poly (ADP [adenosine
      diphosphate]-ribose) polymerase in HL60 cells treated by panaxynol and panaxydol.
      In conclusion, panaxynol and panaxydol have profound effects on growth and
      apoptosis of HL60 cells, suggesting those substances are worthy of further
      exploration as potential anti-cancer agents.

PMID- 21716178
TI  - Gastroesophageal reflux in alcohol-abusing patients.
AB  - INTRODUCTION: Consumption of large amounts of alcohol can promote regurgitation
      of hydrochloric acid into the esophagus and therefore cause symptoms of
      gastroesophageal reflux disease. Most individuals who experience alcohol-related
      health problems are not addicted to alcohol, but they usually show a hazardous
      pattern of alcohol consumption. OBJECTIVES: Objectives The aim of the study was
      to examine the gastrointestinal tract in hazardous drinkers and to establish
      whether such alcohol consumption pattern may be an important risk factor for
      developing gastroesophageal reflux. PATIENTS AND METHODS: Primary care patients
      (n = 2000; mean age 41.1 years) from Warsaw, Poland, responded to 2 surveys:
      AUDIT (Alcohol Use Disorders Identification Test) and Carlsson's questionnaire.
      Patients characterized as hazardous drinkers and having symptoms of reflux
      disease entered the second phase of the study: gastroscopy and pH-metry. The
      results were compared with those obtained in the control group (n = 60), which
      included patients with reflux symptoms but who abstained from alcohol or were
      moderate drinkers. RESULTS: According to the survey results, 18.75% of the study
      group showed a hazardous pattern of alcohol consumption, while 33% had symptoms
      of gastrointestinal reflux disease. A positive pH-metry result was observed in
      87.5% of the hazardous drinkers. Endoscopic features of esophagitis were observed
      in 64% of the patient group and 28% of the control group. Hazardous alcohol
      consumption and male sex may be the risk factors for developing reflux-related
      esophagitis. CONCLUSIONS: Primary care physicians should routinely ask their
      patients about alcohol consumption. Hazardous alcohol drinking may be a risk
      factor for developing reflux disease.

PMID- 21716179
TI  - Biliary strictures after liver transplantation: is percutaneous treatment
      indicated?
AB  - BACKGROUND: Biliary complications are common after orthotopic liver
      transplantation. Our study's aim is to evaluate the efficacy of percutaneous
      treatment of biliary strictures after orthotopic liver transplantation (OLT).
      MATERIAL/METHODS: Sixty-five patients with biliary anastomotic strictures
      received percutaneous transhepatic balloon cholangioplasty (PTBC). Three
      dilatations were performed with a 2- to 4-week period between the procedures.
      Primary and secondary patency were evaluated, with a follow-up between 6 months
      and 6 years. RESULTS: PTBC successfully treated strictures in 52.3% (34/65) of
      cases. The normalization of clinical and biological features was noted at 2.3
      months on average. Neither intercurrent episodes of sepsis nor a worsening of
      liver function were noted during the treatment; a significant complication was
      recorded in 8 patients. No patient needed surgery for the treatment of
      complications after PTBC. Factors related to a successful PTBC included older age
      at transplantation and single-site stricture. There were 7 recurrent strictures
      after PTBC, all successfully treated by nonsurgical procedures. The number of
      dilatations performed affected both the likelihood of success and the long-term
      risk of stricture recurrence. Of the 31 PTBC failures, 19 underwent subsequent
      surgical revision, 8 were treated endoscopically, and 4 were re-transplanted.
      Multifocal stenoses, central hepatic duct involvement, and intrahepatic
      localization resulted associated with treatment failure. CONCLUSIONS: PTBC should
      be considered as a first choice option for treatment of biliary strictures after
      liver transplantation as well as endoscopic treatment. For solitary extrahepatic
      strictures that fail PTBC and ERCP, surgical revision provides good results.

PMID- 21716180
TI  - Malignancy after renal transplantation in the new era of immunosuppression.
AB  - BACKGROUND: This retrospective single-center study was undertaken to assess the
      occurrence of de novo neoplasms in renal transplant recipients according to the
      immunosuppressive regimen and time after transplantation. MATERIAL/METHODS:
      Observation encompassed 1028 patients transplanted between the years 1983-2006
      and followed for 0.5-23 years. Patients with skin cancer other than melanoma were
      excluded due to incomplete data collection. RESULTS: Malignancy appeared in 4.8%
      (49) of the patients after the period of 5.8 +/- 4.7 years at the age of 54 +/-
      13 years. The most common malignancies were urinary tract tumors (22%) and non
      Hodgkin lymphoma with post-transplant lymphoproliferative disease (PTLD) (16%).
      Malignancy occurred in 5.2% of patients on cyclosporine (CSA), azathioprine (AZA)
      and prednisone (P); in 3.4% of patients on mofetil mycophenolate (MMF) with CSA
      and P; in 3.3% of patients on MMF with tacrolimus (TAC) and P; and in 2 of 20
      patients (10%) receiving AZA with P 15 years after transplantation. The regimen
      consisting of CSA, AZA with P could be distinguished by the higher risk of
      malignancy occurrence. The occurrence of malignancy was significantly earlier on
      MMF+TAC+P compared to other regimens (p<0.05). The highest incidence of
      malignancy on AZA with P could be attributed to the longer observation period.
      CONCLUSIONS: In the new era of immunosuppression, despite lower occurrence,
      malignancy tends to appear earlier after the transplantation.

PMID- 21716181
TI  - Limitations of rituximab/IVIg desensitization protocol in kidney transplantation;
      is this better than a tincture of time?
AB  - BACKGROUND: A plasmapheresis-free protocol for desensitization of donor kidney
      transplant candidates with high Calculated Panel Reactive Antibody (CPRA) was
      initiated at our center. The protocol was adopted from previously published work
      by Vo, Jordan et al. MATERIAL/METHODS: Five patients with CPRA of 94 +/- 18%,
      awaiting kidney transplant from living or deceased donors received rituximab (1 g
      * 2 doses) and intravenous immunoglobulin (IVIG 2 g/kg * 2 doses) without
      plasmapheresis. Levels of donor specific antibodies (DSA) and T/B cell
      crossmatches were followed using solid phase flow cytometry. RESULTS: Three out
      of 5 patients were sensitized only to Class II HLA antigens. All patients had
      very high levels of alloantibodies before initiation of the treatment. All of the
      candidates initially demonstrated reduced levels of HLA antibody, but statistical
      significance was only obtained in one patient Class II antibody and in another
      only for Class I. Depletion was transient with observed antibody rebound.
      Rituximab effectively depleted CD20 cells in peripheral blood. None of the
      patients were transplanted due to persistently high levels of antibody and strong
      positive flow cytometry crossmatches. Under this protocol, reduction of HLA
      antibodies in patients with high levels was insufficient. CONCLUSIONS: Highly
      allo-sensitized patients with a CPRA above 85% may not benefit from a combination
      of rituximab-IVIG alone. The previously published protocol does not help all
      patients achieve an acceptable crossmatch. An individualized approach to the
      treatment of highly sensitized patients is still required.

PMID- 21716182
TI  - The occurrence of postreperfusion syndrome in orthotopic liver transplantation
      and its significance in terms of complications and short-term survival.
AB  - BACKGROUND: Postreperfusion syndrome (PRS) is a state of significant hemodynamic
      instability following graft reperfusion during orthotopic liver transplantation
      (OLTx). We aimed to investigate its risk factors and influence on patient outcome
      based on a single centre's experience. MATERIAL/METHODS: A retrospective study on
      a group of 340 patients undergoing OLTx during the period 2005-2008 was
      conducted. Piggy-back technique was employed in 266 cases and classical technique
      in 64. PRS was defined as a decrease in mean arterial pressure greater than 30%
      below the baseline for a minimum of 1 minute during first 5 minutes of the
      reperfusion. Logistic regression analysis, Mann-Whitney test and 2-sample
      proportion test were used. P<0.05 was considered statistically significant.
      RESULTS: PRS occurred in 12.1% of patients. We observed correlations between PRS
      and the following: longer cold ischemia time, operation with classical technique,
      longer duration of the operation, higher intraoperative erythrocytal mass (EM)
      and fresh frozen plasma (FFP) requirements, more frequent early post-operative
      complications, and lower 1-year survival. Retransplantation was needed nearly
      twice as often in the PRS-group, but the correlation was not statistically
      significant (the group was very small, as only 8 patients requested re-OLTx). The
      study did not demonstrate any statistically significant relationship between PRS
      and donors' age, recipients' age or sex, duration of the hospitalization, and
      occurrence of complications after discharge. CONCLUSIONS: PRS occurrence seems to
      be associated with higher mortality rate and worse patient outcome. The study
      revealed a few risk factors that could be relevant in the prevention of PRS.

PMID- 21716183
TI  - Feasibility of routine paranasal sinus CT-scans in preoperative transplant
      patients.
AB  - BACKGROUND: Paranasal Sinus (PNS) CT- scans are routinely performed for screening
      of sinusitis in patients scheduled for organ transplant at the University
      Hospital Graz. This study was performed to evaluate whether routine PNS CT-scans
      are necessary in every transplant patient or in selected cases only, because
      clear evidence is missing in literature. MATERIAL/METHODS: 142 patients (113
      male, 29 female) were included in this retrospective patient chart study.
      RESULTS: The majority of patients (n=142) were scheduled for liver transplant
      (n=79). Of all patients (n=142), 50 (35.2%) had normal PNS CT-scans and 92
      (64.8%) had a pathologically changed PNS-scan. Seventy-one out of these 92
      (77.2%) patients did not show clinical symptoms of sinusitis nor changes in
      diagnostic endoscopy, 21 (22.8%) patients did have symptoms of sinusitis and
      diseased PNS CT-scans. Three out of 71 (4.2%) without symptoms but pathologic CT
      scans compared to 7/21 (33.3%) patients with symptoms and pathological CT-scans
      underwent endoscopic paranasal sinus surgery (FESS). All patients operated
      suffered from chronic sinusitis, none had mycotic or neoplastic disease in
      definite histology. CONCLUSIONS: Since there was a high rate (77.2%) of
      pathological CT scans unrelated to sinusitis symptoms these findings should be
      considered as accidental. In our opinion routine paranasal sinus CT scans are not
      feasible in patients scheduled for organ transplant according to high rate of
      false positive results.

PMID- 21716184
TI  - Comparison of immediate renal dysfunction in split and partial liver
      transplantation versus full size liver transplantation in Shiraz transplant
      centre.
AB  - BACKGROUND: Renal dysfunction (RD) is a common complication following liver
      transplantation. Postoperative renal function after split liver transplant (SLT)
      and (partial living related liver transplant) (LRLT) has not been well studied
      yet. MATERIAL/METHODS: Renal function immediately after surgery was analyzed
      retrospectively in 32 patients that received SLT and LRLT. Serum creatinine (SCr)
      was measured before surgery, and, after transplantation daily during the first
      week and at 14, 21, and 28 days after transplantation. Patient's medical records
      were reviewed to find clinical data;Model for end-stage liver disease (MELD)
      score, Child-Turcotte-Pugh score (CTP) class, the length of surgery, length of
      anhepatic phase, hospital and ICU admission, incidence of acute rejection, renal
      dysfunction, and sepsis. These data compared between groups. RESULTS: Length of
      surgery and anhepatic phase was longer in SLT and LRLT group (P<0.05). The
      incidence of acute rejection, reoperation, and complication such as sepsis was
      higher in SLT and LRLT group than FSLT group (P<0.05). There were no significant
      difference between groups with respect to MELD, CTP score, the need for
      transfusions, the length of admission to the hospital and ICU. Immunosuppression
      regimens were similar in both groups. RD developed in 25.8% of SLT and LRLT
      patients, but in only 9.5% of FSLT patients (p=0.063). The requirement for RRT in
      SLT and LRLT group (12.5%) was greater than that in the FSLT group (2.3%);
      P=0.20. CONCLUSIONS: Although the number of patients studied was small, our data
      suggests a higher incidence of RD in patients receiving SLT and LRLT.

PMID- 21716185
TI  - Factors influencing QTc interval prolongation during kidney transplantation.
AB  - BACKGROUND: During renal transplantation, factors causing disturbances of the
      repolarization process, defined by the QT interval, may lead to ventricular
      arrhythmias. The aim of this study was to determine a relationship between QT
      interval prolongation and metabolic homoeostasis, and durations of cold ischemia
      time (CIT) and warm ischemia time (WIT) during renal transplantation.
      MATERIAL/METHODS: From among 198 consecutive renal transplant patients, 68 (mean
      age 45 +/- 12 years) were included in a prospective observational pilot study.
      Prior to the procedure, arterial blood gas analysis was performed, and digital
      Holter ECG monitoring was applied and continued for 12 hours. Subsequent arterial
      blood gas analysis was performed 30 minutes after graft reperfusion. RESULTS: QTc
      changed dynamically and significantly during the perioperative period.
      Ventricular arrhythmias were observed only during graft reperfusion. Recordings
      showed that 33 out of 68 patients had ventricular extrasystoles, and non
      sustained ventricular tachycardia was observed in 2 patients. No patients
      presented with hemodynamic instability. There was no statistical correlation
      between CIT or WIT and the difference (delta) between the final and initial
      values of the pH, potassium and lactate levels, QTc range, maximal QTc or QTc
      measured at the predefined time points. CONCLUSIONS: The renal transplantation
      procedure carries a high risk of ventricular repolarization period disturbances
      that can lead to life-threatening tachyarrhythmias despite optimal hemodynamic or
      metabolic status and independent of CIT and WIT.

PMID- 21716186
TI  - Single-dose thymoglobulin induction in living-donor renal transplantation.
AB  - BACKGROUND: The use of Thymoglobulin induction therapy in living-donor renal
      transplantation remains controversial. We aimed to evaluate outcomes in living
      related donor (LRD) and living unrelated donor (LURD) renal transplants with
      Thymoglobulin induction. MATERIAL/METHODS: We retrospectively analysed the
      outcome of all Thymoglobulin induced living-donor renal transplants performed at
      our centre from 2002 to 2010. RESULTS: We reviewed 100 living-donor renal
      transplants (LRD=60; LURD=40) who received thymoglobulin induction (single dose,
      1.5 mg/kg bodyweight) with a mean follow-up of 52.6 +/- 31.9 months. Although
      baseline characteristics of the LRD and LURD groups were similar, differences
      were noted for recipient age, gender, and HLA-matching. Overall, the estimated 5
      year patient survival was 92% and graft survival, 83%. The 1- and 5-year patient
      survival rates were 97.4% and 90.7% for LRD and 98.3% and 92.2% for LURD
      (P=0.79), respectively. Cumulative graft survival (LRD vs. LURD) rates were 93%
      vs. 95% after 1 year and 80% vs. 88% after 5 years (P=0.53). Kidney graft
      function was comparable for both the groups. Acute rejection was observed in 17%
      LRD and 35% LURD patients (P=0.035). Further, 10% of the patients experienced
      delayed graft function (LRD 11% vs. LURD 8%; P=NS). Rates of cytomegalovirus
      (CMV) infection (10%), polyomavirus infection (5%), malignancy (4%), and
      lymphoproliferative disorder (0%) were low, with no differences between the 2
      groups. CONCLUSIONS: Single-dose thymoglobulin induction in living-donor renal
      transplantation was associated with high patient and graft survival without
      increasing the risk of infections or malignancy and without significant
      differences between LRD and LURD patients.

PMID- 21716187
TI  - Generic formulation of Cyclosporine A, Equoral(r), in de novo kidney transplant
      recipients: five-year follow-up.
AB  - BACKGROUND: Equoral((r)) is a generic formulation of Cyclosporine A (CsA), which
      is significantly cheaper than the original medicine. Our center participated in
      the clinical trial designed to evaluate the efficacy and safety of Equoral((r))
      in kidney transplant recipients in the first 9 months after a transplant
      procedure. The aim of our paper is to present the 5-year follow-up of patients
      who participated in the study and were monitored in our center. MATERIAL/METHODS:
      We performed intention-to-treat retrospective analysis of 20 de novo kidney
      transplant recipients who received Equoral(r)-based immunosuppressive regimen and
      were monitored in our department for 5 years after transplantation. RESULTS: The
      5-year patient and graft survival was 90%, and the frequency of acute rejection
      was 15%. In 80% of patients, the initial immunosuppressive regimen had to be
      changed. CONCLUSIONS: In our group of kidney transplant recipients,
      immunosuppression based on generic formulation of CsA had excellent 5-year
      patient and graft survival and effectively prevented acute rejection episodes.
      However, most patients needed modification of the initially administered
      immunosuppressive regimen.

PMID- 21716188
TI  - Evaluation of the HeartMate IITM left ventricular assist device in obese heart
      failure patients: effects on weight loss.
AB  - BACKGROUND: The purpose of this study is to evaluate the effect on weight loss of
      the newer generation continuous flow HeartMate IITM left ventricular assist
      device (VAD) in obese heart failure (HF) patients. MATERIAL/METHODS: We
      retrospectively reviewed 3-year surgical data from a large heart transplant
      facility and identified obese patients with advanced heart failure who underwent
      successful implantation of either the HeartMate XVE((r)) or the HeartMate II((r))
      VAD. For each patient weight and BMI at time of VAD implantation and at 6 months
      post-operatively were documented. Between group comparison was achieved with
      Student's T tests. RESULTS: We identified 14 patients who had received the
      HeartMate XVETM and 8 who had received the HeartMate IITM. At 6 months, patients
      who received a HeartMate XVETM demonstrated a significant reduction in mean body
      weight (249.6 +/- 35.4lbs vs. 217.4 +/- 20.5 lbs; P<0.05), while patients who
      received the HeartMate IITM demonstrated no significant change in weight (234.5
      +/- 41.7 lbs vs. 234.7 +/- 43.0lbs; P=0.3). CONCLUSIONS: The HeartMate XVETM
      results in significant reductions in weight at 6 months in obese patients with
      heart failure while the HeartMate II does not. Further research is necessary to
      better understand the effects of VADs on weight loss in obese HF patients.

PMID- 21716189
TI  - Effect of tacrolimus on energy metabolism in human umbilical endothelial cells.
AB  - BACKGROUND: Tacrolimus has a wide spectrum of adverse effects, including
      neurotoxic and vascular events. Vascular dysfunction due to interference of
      tacrolimus with mitochondrial function in endothelial cells may contribute to
      these adverse reactions. MATERIAL/METHODS: We evaluated the impact of clinically
      relevant tacrolimus concentrations after 48 hours on energy metabolism in
      cultured human umbilical vein endothelial cells (HUVEC): Global fatty acid
      oxidation (FAO), activities of respiratory chain complexes I-V (RC),
      citratesynthase (CS), glycolytic enzymes and energy rich phosphates were
      measured. RESULTS: RC-complexes II+III were significantly compromised at 100
      nmol/L and CS at 10, 25 and 50 nmol/L, while global FAO was not significantly
      impaired. Cellular lactate-dehydrogenase (LDH)-, hexokinase- and
      phosphofructokinase-activities were not altered; AMP levels increased after 48
      hours at 200 nmol/L while energy charges remained stable. No cellular toxicity,
      assessed by light microscopy and LDH leakage was observed even at highest
      tacrolimus concentrations. CONCLUSIONS: Tacrolimus partially impaired
      mitochondrial function in HUVEC at the level of RC-complexes II+III and CS. Part
      of tacrolimus toxicity and vascular dysfunction may arise from these metabolic
      alterations. To some extent, energy balance could be maintained by FAO and
      cytosolic energy production; energy consumption might be economized. Although
      only demonstrated for endothelial cells, it is conceivable that such effects will
      alter energy metabolism in different tissues with high oxidative demands.

PMID- 21716190
TI  - Calcineurin inhibitor-based and free regimens have distinct gene expression
      patterns in subclinical graft fibrosis.
AB  - BACKGROUND: Chronic nephrotoxic effects of calcineurin inhibitors may be
      responsible for late allograft dysfunction and reduced allograft half-life.
      Mammalian target of rapamycin inhibitors (mTOR-i's), a newer class of
      immunosuppressant, do not have the chronic nephrotoxic effects shown with
      calcineurin inhibitors (CNI). Whether these drug classes have distinct features
      at the molecular level is not clear. MATERIAL/METHODS: Difference in gene
      expression profiles of kidney graft protocol biopsies from patients treated with
      CNI or mTOR-i's were investigated. Biopsies from patients using CNI (n=4) and
      mTOR-i-based treatments (n=4) were analyzed. The control group consisted of 5
      biopsies obtained at the time of implantation (zero hour). Microarray
      hybridization was performed using the Affymetrix(r) GeneChip U133 plus 2.0 Array.
      RESULTS: In the CNI and mTOR-i groups, 64 up-regulated and 119 down-regulated
      genes were found compared to control subjects. A total of 29 genes in the CNI
      group and 101 genes in the mTOR-i group were up-regulated compared to each other.
      CONCLUSIONS: Despite similar clinical courses and histopathological appearances,
      different treatment strategies cause different gene expression profiles in kidney
      transplantation.

PMID- 21716191
TI  - Steroid-free maintenance of islet allografts using mycophenolate mofetil and
      cyclosporine in the non-human primate.
AB  - BACKGROUND: Islet transplantation continues to be a promising treatment for type
      1 diabetes, however, numerous limitations still prevent its widespread use. Many
      immunosuppressive medications used for islet transplantation are known to be
      diabetogenic. The goal of this study is to evaluate the short-term follow-up (90
      day) of a steroid-free maintenance immunosuppression protocol of mycophenolate
      mofetil (MMF) and cyclosporine (CSA) in non-human primate islet
      allotransplantation. MATERIAL/METHODS: Diabetes was induced in the primate Macaca
      fascicularis via total pancreatectomy. Freshly isolated islets were
      autotransplanted (n=5) or allotransplanted (n=5) into the portal vein.
      Immunosuppression consisted of induction with rabbit anti-thymocyte globulin
      (ATG) and prednisone. CSA (25 mg/daily) and MMF (250 mg daily) were used for
      maintenance and given orally once daily throughout the 90 day study period.
      Fasting blood glucose measurements were used to monitor graft function.
      Intravenous glucose tolerance tests (IVGTT) were performed prior to
      pancreatectomy and at the study endpoint. RESULTS: Average fasting blood glucose
      levels were elevated in diabetic controls (313.6 mg/dl +/-51.8) and untreated
      allograft recipients (257 mg/dl +/-61.0) post-transplant. Auto-transplanted
      animals and allograft recipients treated with immunosuppression, on the other
      hand, maintained normoglycemia (74.5 mg/dl +/-20.9, 62.3 mg/dl +/-4.40)
      throughout the follow-up period. Additionally, beta cell function and first phase
      insulin secretion did not differ significantly between auto-graft and
      immunosuppressed allo-graft recipients post-transplant. CONCLUSIONS: We conclude
      that this steroid-free maintenance immunosuppression regimen is effective in
      maintaining islet allograft survival in the non-human primate and offers
      comparable graft function to that of autografts for up to 3 months post
      transplant.

PMID- 21716192
TI  - Prolactin (PRL) reduces the release of transaminases from the isolated pig liver.
AB  - BACKGROUND: This study investigated methods of increasing the effectiveness of
      preservation solutions. Recently, it has been reported that solution
      effectiveness can be improved by the addition of prolactin (PRL). This study
      determines the effect of prolactin (PRL) on the amount and release rate of
      alanine aminotransferase (ALAT) and aspartate aminotransferase (AST) from liver
      during its 24-hour preservation period. MATERIAL/METHODS: Isolated porcine liver
      was kept in the HTK (histidine-tryptophan-ketoglutaric acid) solution with and
      without PRL. Once infusion and the 24-hour preservation period had been finished,
      samples of the preservation solution were taken and the amounts of released
      indicator enzymes were determined. RESULTS: Aminotransferases were released from
      hepatocytes to the preservation solution at various rates. ALT was released much
      faster into the solution without PRL (k=-0.1230 [U/l/h-1]) and slower with PRL
      (k=-0.0895 [U/l/h-1]). The enzyme was released into the solution with PRL at a
      27% slower rate. Similar results were obtained when the release rate of AST was
      analyzed. AST was more quickly released into the solution without PRL (k=-0.0642
      [U/l/h-1]), and more slowly with PRL (k=-0.0205 [U/l/h-1]). The enzyme was
      released into the PRL-containing solution at a 68% slower rate. CONCLUSIONS: The
      obtained results indicate that the addition of PRL significantly lowers the
      amount of aminotransferases released from hepatocytes and also lessens their
      release rate, as it significantly affects the time of efficient in vitro storage
      of the liver.

PMID- 21716193
TI  - Acute kidney injury after procedures of orthotopic liver transplantation.
AB  - The incidence of acute kidney injury (AKI) after orthotopic liver transplantation
      (OLT) ranges from 40 to 70%, with 8-17% of these patients requiring renal
      replacement therapy. The aetiology of this syndrome is multi-factorial, and its
      most common cause is ischaemia in the early postoperative period, and toxicity of
      immunosuppressive drugs and infectious complications at long term. AKI
      significantly increases the risk of death and development of chronic renal
      failure in the late post-OLT period. We discussed in short in our work the risk
      factors of AKI, diagnostics and clinical management in this group of patients.

PMID- 21716194
TI  - TIPS stent migration into the heart with 6-year follow-up.
AB  - BACKGROUND: The transjugular intrahepatic portosystemic shunt (TIPS) is widely
      used for the treatment of portal hypertension in adults, but no studies have
      defined the best approach to treat portal hypertension in pediatric patients.
      Pediatric use of TIPS is rare even in large centers of adult practice. The
      migration of stents has also been reported as a complication in adults. There is
      no standard way to treat this type of complication, and it is not always clear
      whether immediate removal or watchful waiting is safer for the patient. CASE
      REPORT: We report the case of an 11-year-old patient who underwent urgent TIPS
      implantation due to variceal bleeding, after unsuccessful sclerotherapy. During
      the procedure, due to the deep impact of the stent, a second, telescopic, stent
      was inserted. The portal pressure decreased, no further bleeding occurred, and
      the patient was listed for transplantation. Three weeks later a routine chest X
      ray discovered the migration of the second stent into the right ventricle. No
      interventional radiological removal or open heart surgery was available for the
      transplant waiting list patient. The patient underwent uneventful combined liver
      kidney transplantation. During the 6-year follow-up period the child had no signs
      of hemodynamic instability, and his somatic and mental development were
      appropriate. CONCLUSIONS: To our knowledge this case is the first publication on
      a heart-impacted TIPS stent in a child. The watchful waiting was justified by
      uneventful combined liver-kidney transplantation and long-term follow-up. This
      case also underlines the need for best practice guidelines in pediatric portal
      hypertension.

PMID- 21716195
TI  - Collapsing glomerulopathy in a renal transplant recipient: potential molecular
      mechanisms.
AB  - BACKGROUND: In this case report, we describe a predisposed renal transplant
      patient who developed FSGS with cellular and collapsing features after sirolimus
      exposure and discuss the potential molecular mechanisms. CASE REPORT: A 35-year
      old African American female with end stage renal disease due to lupus nephritis
      received a living related renal transplant from a brother. She had immediate
      function achieved serum creatinine level of 1.7 mg/dl post day 4. Following a
      slow rise in the creatinine, first renal allograft biopsy performed on post op
      day 14 that showed thrombotic microangiopathy (TMA) involving arterioles and
      glomerular capillaries without any sign of rejection. The serological work up was
      negative for donor specific and antiphospholipid antibodies. The TMA was
      attributed to tacrolimus which was subsequently discontinued. It was replaced
      with sirolimus with loading dose of 10mg once and then 5 mg daily maintenance
      dose at day 21. At day 35, the patient was noted to have nephrotic range
      proteinuria, 12 gm/24 hrs. A second renal biopsy performed that revealed de novo
      focal segmental glomerulosclerosis with cellular and collapsing features, mild
      mesangial proliferative glomerulonephritis with immunoflourescence consistent
      with early recurrence of lupus nephritis ISN/RPS class 2. The etiology of
      cellular and collapsing FSGS was thought to be related to sirolimus based on
      timing of exposure and negative work up for secondary causes of collapsing FSGS.
      Sirolimus was switched to cyclosporine. At day 105, proteinuria decreased to 1.6
      grams/day and serum creatinine leveled off 1.6 mg/dL. CONCLUSIONS: We report a
      case of possible sirolimus-induced collapsing FSGS in a renal transplant
      recipient who may have been predisposed to develop a podocytopathy possibly due
      to TMA and altered WT1 expression resulting from m-TOR exposure.

PMID- 21716196
TI  - Liver allograft with hemangioma in pediatric living donor liver transplantation.

PMID- 21716197
TI  - Occupational aviation fatalities--Alaska, 2000-2010.
AB  - Aircraft crashes are the second leading cause of occupational deaths in Alaska;
      during the 1990s, a total of 108 fatal aviation crashes resulted in 155
      occupational fatalities. To update data and identify risk factors for
      occupational death from aircraft crashes, CDC reviewed data from the National
      Transportation Safety Board (NTSB) and the Alaska Occupational Injury
      Surveillance System. During 2000--2010, a total of 90 occupational fatalities
      occurred as a result of 54 crashes, an average of five fatal aircraft crashes and
      eight fatalities per year. Among those crashes, 21 (39%) were associated with
      intended takeoffs or landings at landing sites not registered with the Federal
      Aviation Administration (FAA). Fifteen crashes (28%) were associated with
      weather, including poor visibility, wind, and turbulence. In addition, 11 crashes
      (20%) resulted from pilots' loss of aircraft control; nine (17%) from pilots'
      failure to maintain clearance from terrain, water, or objects; and seven (13%)
      from engine, structure, or component failure. To reduce occupational fatalities
      resulting from aircraft crashes in the state, safety interventions should focus
      on providing weather and other flight information to increase pilots' situational
      awareness, maintaining pilot proficiency and decision-making abilities, and
      expanding the infrastructure used by pilots to fly by instruments.

PMID- 21716198
TI  - Adult blood lead epidemiology and surveillance--United States, 2008-2009.
AB  - Lead exposure can result in acute or chronic adverse effects in multiple organ
      systems, ranging from subclinical changes in function to symptomatic, life
      threatening toxicity. Despite improvements in public health policies and
      substantial reductions in blood lead levels (BLLs) in adults, lead exposure
      remains an important health problem worldwide. Approximately 95% of all elevated
      BLLs reported among adults in the United States are work-related, and recent
      research has raised concerns regarding the toxicity of BLLs as low as 5 MUg/dL.
      CDC's state-based Adult Blood Lead Epidemiology and Surveillance (ABLES) program
      tracks laboratory-reported elevated BLLs. To update rate trends and identify
      industry subsectors and nonoccupational activities with high lead exposures, CDC
      collected and analyzed 2008--2009 data from 40 state ABLES programs. The results
      of that analysis indicated that a decline in the prevalence of elevated BLLs
      (>=25 MUg/dL) was extended, from 14.0 per 100,000 employed adults in 1994 to 6.3
      in 2009. Industry subsectors with the highest numbers of lead-exposed workers
      were battery manufacturing, secondary smelting and refining of nonferrous metals,
      and painting and paper hanging. The most common nonoccupational exposures to lead
      were shooting firearms; remodeling, renovating, or painting; retained bullets
      (gunshot wounds); and lead casting. The findings underscore the need for
      government agencies, employers, public health professionals, health-care
      providers, and worker-affiliated organizations to increase interventions to
      prevent workplace lead exposure, and the importance of conducting lead exposure
      surveillance to assess the effectiveness of these interventions.

PMID- 21716199
TI  - Update on vaccine-derived polioviruses--worldwide, July 2009-March 2011.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide.
      The live, attenuated oral poliovirus vaccine (OPV) has many advantages favoring
      its use in polio eradication: it is administered easily by mouth; confers
      intestinal immunity, making recent OPV recipients resistant to infection by wild
      polioviruses (WPVs); provides long-term protection against paralytic disease
      through durable humoral immunity; and is inexpensive. Despite its many
      advantages, OPV use carries the risk for occurrence of rare cases of vaccine
      associated paralytic poliomyelitis among immunologically normal OPV recipients
      and their contacts and the additional risk for emergence of vaccine-derived
      polioviruses (VDPVs). Because of these risks, OPV use will be discontinued
      worldwide once the goal of eradicating all WPV transmission is achieved. VDPVs
      can cause polio outbreaks in areas with low OPV coverage and can replicate for
      years in immunodeficient persons; therefore, strategies to strengthen global
      polio immunization and surveillance are needed to limit emergence of VDPVs. This
      report updates previous surveillance summaries and describes VDPVs detected
      worldwide during July 2009--March 2011 and reported as of June 20, 2011. Three
      new outbreaks of circulating VDPVs (cVDPVs), ranging in size from six to 16
      cases, were identified in Afghanistan, Ethiopia, and India; three previously
      identified outbreaks in Nigeria, Democratic Republic of Congo (DRC), and Somalia
      continued through late 2010 or into 2011 and resulted in 355, 37, and 13 total
      cases, respectively; two countries experienced importations of cVDPVs from
      Nigeria; nine newly identified paralyzed immunodeficient persons in seven middle
      income and developing countries were found to excrete VDPVs; and VDPVs were found
      among persons and environmental samples in 15 countries. With the use of
      alternate OPV formulations since 2005 and with enhanced poliovirus surveillance
      sensitivity and laboratory screening, the number of identified cVDPV outbreaks
      per year has increased over time . To prevent VDPV emergence and spread, all
      countries should maintain high poliovirus vaccination coverage against all three
      poliovirus serotypes. Sensitive poliovirus surveillance to detect VDPVs will
      continue to increase in importance.

PMID- 21716200
TI  - Notes from the field: Multiple cases of measles after exposure during air travel-
      Australia and New Zealand, January 2011.
AB  - In January 2011, measles was diagnosed in three New Zealand residents recently
      returned from a 17-day trip to Singapore and the Philippines. On January 11, they
      had flown on a 7.5-hour flight from Singapore to Brisbane, Australia, remained in
      a transit lounge for 9.5 hours, and then continued on a 4-hour flight to
      Auckland, New Zealand. Searches in Australia and New Zealand for secondary cases
      among passengers on either flight resulted in the identification of three cases
      among passengers on the Singapore-to-Brisbane flight and five cases among
      passengers on the Brisbane-to-Auckland flight.

PMID- 21716201
TI  - Long-term exposure to microwave radiation provokes cancer growth: evidences from
      radars and mobile communication systems.
AB  - In this review we discuss alarming epidemiological and experimental data on
      possible carcinogenic effects of long term exposure to low intensity microwave
      (MW) radiation. Recently, a number of reports revealed that under certain
      conditions the irradiation by low intensity MW can substantially induce cancer
      progression in humans and in animal models. The carcinogenic effect of MW
      irradiation is typically manifested after long term (up to 10 years and more)
      exposure. Nevertheless, even a year of operation of a powerful base transmitting
      station for mobile communication reportedly resulted in a dramatic increase of
      cancer incidence among population living nearby. In addition, model studies in
      rodents unveiled a significant increase in carcinogenesis after 17-24 months of
      MW exposure both in tumor-prone and intact animals. To that, such metabolic
      changes, as overproduction of reactive oxygen species, 8-hydroxi-2-deoxyguanosine
      formation, or ornithine decarboxylase activation under exposure to low intensity
      MW confirm a stress impact of this factor on living cells. We also address the
      issue of standards for assessment of biological effects of irradiation. It is now
      becoming increasingly evident that assessment of biological effects of non
      ionizing radiation based on physical (thermal) approach used in recommendations
      of current regulatory bodies, including the International Commission on Non
      Ionizing Radiation Protection (ICNIRP) Guidelines, requires urgent reevaluation.
      We conclude that recent data strongly point to the need for re-elaboration of the
      current safety limits for non-ionizing radiation using recently obtained
      knowledge. We also emphasize that the everyday exposure of both occupational and
      general public to MW radiation should be regulated based on a precautionary
      principles which imply maximum restriction of excessive exposure.

PMID- 21716202
TI  - In vivo and in vitro antitumor effects of nutrient mixture in murine leukemia
      cell line P-388.
AB  - AIM: Leukemia is characterized by uncontrolled marrow cell proliferation and
      metastatic foci. We investigated the antitumor potential of a nutrient mixture on
      malignant leukemia P-388 cells. METHODS: The nutrient mixture containing lysine,
      proline, ascorbic acid, green tea extract and other nutrients is formulated to
      target key pathways in cancer progression. The cells were treated with the
      mixture, and tested at doses 0, 10, 50, 100, 500 and 1000 MUg/ml in triplicates.
      The effects were evaluated by cell proliferation, Matrigel invasion, cell
      morphology and apoptosis. The in vivo effect was measured in male nude mice (n =
      12) inoculated with P-388 cells. After randomly dividing in two groups, each
      group was fed regular and the nutrient mixture supplemented diet and the mice
      were sacrificed after four weeks. RESULTS: The nutrient mixture decreased P-388
      cell proliferation at 500 and 1000 MUg/ml. Only 10% cells were viable at 1000
      MUg/ml. Matrigel invasion was significantly inhibited in a dose dependent manner
      with virtually total inhibition at 1000 MUg/ml. Cell morphological features
      notably changed with dose increase to 1000 MUg/ml. Analysis of apoptotic cells on
      live green caspase kit exhibited gradual increase with the increasing dose of the
      nutrient mixture, and at 1000 MUg/ ml 92% of P-388 cells were in late apoptosis.
      Tumors in the group of mice supplemented with the nutrient mixture had 50% lower
      weight compared to the tumors in control group (p = 0.0105). Histopathologically,
      both the groups of tumors were similar, yet size of tumors in the group treated
      with the nutrient mixture was considerably smaller. CONCLUSION: These results
      indicate that the nutrient mixture exhibited significant action against multiple
      targets in P-388 leukemia and may have potential in human leukemia.

PMID- 21716203
TI  - Distribution and accumulation of liposomal form of doxorubicin in breast cancer
      cells of MCF-7 line.
AB  - AIM: To study distribution and accumulation of liposomal form of doxorubicin in
      human breast cancer cells of MCF-7 line and Dox-resistant subline MCF-7/Dox.
      METHODS: High performance liquid chromatography and laser confocal microscopy
      were used. RESULTS: It has been shown that conventional form of doxorubicin was
      more efficiently delivered to the MCF-7 cells already after 30 min of incubation
      amounting to its maximum concentration after 4 h. MCF-7/Dox cells are
      characterized by lower doxorubicin accumulation rate compared with parental
      cells. The quantity of accumulated liposomal form of doxorubicin is high in MCF-7
      cells, and, what is important, Dox-resistant cells accumulated higher levels of
      liposomal form of doxorubicin than its conventional form. CONCLUSION: It has been
      shown that intracellular distribution and accumulation of liposomal forms of
      doxorubicin in parental and Dox-resistant MCF-7 cells differs from that of
      conventional doxorubicin.

PMID- 21716204
TI  - Telomerase reverse transcriptase (TERT) expression and role of vincristine
      sulfate in mouse model of malignancy related peritoneal ascites: an experimental
      metastatic condition.
AB  - AIM: To evaluate the efficacy of intraperitoneal vincristine administration into
      ascitic sarcoma-180 bearing mice as a model of human malignant ascites regarding
      various peritoneal/retroperitoneal sarcomatosis, and to evaluate the
      flowcytometric telomerase reverse transcriptase expression for the diagnostic and
      prognostic purposes. METHODS: Present study included disease induction by
      intraperitoneal homologous ascitic sarcoma-180 transplantation followed by in
      vivo intraperitoneal drug administration to study mitotic index, flowcytometric
      cell cycle and telomerase reverse transcriptase expression pattern, erythrosin-B
      dye exclusion study for malignant cell viability assessment. Besides, in vitro
      malignant ascite culture in presence and absence of vincristine sulfate and
      survival study were also taken into consideration. RESULTS: Intraperitoneal
      vincristine administration (concentration 0.5 mg/kg body weight) significantly
      diminished the mitotic index in diseased subjects in comparison to untreated
      control subjects. Treated group of animals showed increased life span and median
      survival time. Cell viability assessment during the course of drug administration
      also revealed gradual depression on cell viability over time. Flowcytometric cell
      cycle analysis showed a good prognostic feature of chemotherapeutic
      administration schedule by representing high G2/M phase blocked cells along with
      reduced telomerase reverse transcriptase positive cells in treated animals.
      CONCLUSION: We conclude that long term administration of vincristine sulfate in
      small doses could be a good pharmacological intervention in case of malignant
      peritoneal ascites due to sarcomatosis as it indirectly reduced the level of
      telomerase reverse transcriptase expression in malignant cells by directly
      regulating cell cycle and simultaneously increased the life expectancy of the
      diseased subjects.

PMID- 21716205
TI  - Efficacy of natural L-asparagine in the complex therapy for malignant tumors in
      experimental studies.
AB  - AIM: To study the influence of natural L-asparagine on the efficacy of cytostatic
      therapy for malignant tumors in experimental investigations. MATERIALS AND
      METHODS: Female C57B1/6 mice weighing 18-20 g were selected for the experiments.
      Lewis' lung carcinoma (LLC) and melanoma B16 cells were used in the study.
      Animals were inoculated with tumor cells intramuscularly. Solution of L
      asparagine in a volume of 0.2 ml per mouse (in appropriate doses) was
      administered to the animals using gastric probe, daily, for 14 days.
      Cyclophosphane was administered intraperitoneally in total doses of 180 mg/kg and
      90 mg/kg on days 3 and 7 after tumor implantation. The percentage of tumor growth
      inhibition was calculated and inhibition index and frequency of metastasis were
      assessed. RESULTS: It has been shown that despite low activity of L-asparagine
      with regard to primary tumor, the level of metastasis inhibition is rather high
      (up to 91% depending on experimental model, therapy regimen and follow-up
      period). The analysis of previously obtained data and our studies indicate that L
      asparagine derived from burdock (Arctium lappa) root has not only its own
      antimetastatic activity but it is also able to increase antimetastatic activity
      of cyclophosphane partially reducing toxic effect of cyclophosphane on the
      organism without decreasing its antitumor and antimetastatic activities.
      CONCLUSION: L-asparagine derived from burdock (Arctium lappa) root can be
      effective in the complex anticancer therapy with the use of appropriate
      chemotherapy doses and regimens.

PMID- 21716206
TI  - Quantitative analysis of SLC34A2 expression in different types of ovarian tumors.
AB  - AIM: The main purpose of this study was to estimate the SLC34A2 gene expression
      in normal ovary and different types of ovarian tumors. METHODS: We have
      investigated SLC34A2 gene expression level in papillary serous, endometrioid,
      unspecified adenocarcinomas, benign tumors, and normal ovarian tissues using real
      time PCR analysis. Differences in gene expression were calculated as fold changes
      in gene expression in ovarian carcinomas and benign tumors compared to normal
      ovary. RESULTS: We have found that SLC34A2 gene was highly expressed in well
      differentiated endometrioid and papillary serous ovarian carcinomas compared to
      low-differentiated endometrioid carcinomas, benign serous cystoadenomas and
      normal ovary. Analysis of SLC34A2 gene expression according to tumor
      differentiation level (poor- and well-differentiated) showed that SLC34A2 is up
      regulated in well differentiated tumors. CONCLUSION: Upregulation of SLC34A2 gene
      expression in well-differentiated tumors may reflect cell differentiation
      processes during ovarian cancerogenesis and could serve as potential marker for
      ovarian cancer diagnosis and prognosis.

PMID- 21716207
TI  - Identifying the stage of new CLL patients using TK, ZAP-70, CD38 levels.
AB  - Serum thymidine kinase (TK), zeta-associated protein of 70 kDa (ZAP-70) and CD38
      levels have been shown to be correlated with survival in chronic lymphocytic
      leukaemia (CLL). AIM: To investigate the possible correlations between TK, ZAP-70
      and CD38 levels as prognostic markers in new diagnosed Rai stages of CLL
      patients. METHODS: 120 CLL patients were enrolled. ELISA was used to measure
      serum TK level, flow cytomerty - to determine ZAP-70 and CD38 expression applying
      ZAP-70 Kit and monoclonal antibody to CD38, respectively. RESULTS: Significantly
      higher levels of TK were found in the high progression group of CLL patients that
      corresponded to stage II (Rai classification). An elevated level of TK, CD38 and
      ZAP-70 together was also found in the II stage. The coefficient of correlation
      between CD38 and ZAP-70 is reliable (p < 0.001). There is also a correlation
      between the level of TK and the disease stage (p < 0.05). Other parameters do not
      show this correlation. CONCLUSION: The determination of TK, ZAP-70 and CD38
      together allows patients susceptible to a possible stage of the disease, to be
      identified. Estimation of the factors at an early stage of the disease may allow
      an earlier commencement of treatment.

PMID- 21716208
TI  - Quantitative real time PCR analysis of apoptosis-related gene expression in
      leukemias in Ukrainian patients.
AB  - BACKGROUND: The complete medical consequences of the long-term exposure of
      population to ionizing radiation in post-Chernobyl period are still a
      controversial issue. The molecular biological analysis of malignant diseases of
      hematopoietic and lymphoid tissues in contaminated territories requires the
      precise diagnosis based on criteria of novel classifications. AIM: To analyze the
      relative gene expression of six apoptosis-related genes in different types of
      tumors of hematopoietic and lymphoid tissues in patients living in areas of
      Ukraine contaminated with radionuclides in post-Chernobyl period. MATERIAL AND
      METHODS: The samples of the peripheral blood and bone marrow of 189 Ukrainian
      leukemia patients and 16 patients with reactive lymphocytosis were analyzed
      morphologically and immunocytochemically for precise delineation of the main
      forms and cytological variants of hematological malignancies according to new WHO
      classification. Expression of six apoptosis-related genes was analyzed in the
      individual samples of 9 different groups of malignant diseases of hematopoietic
      and lymphoid tissues and one group of patients with reactive lymphocytosis by
      quantitative RT-PCR. Expression of genes was assessed relative to that in control
      group of healthy donors. RESULTS: Up-regulation of six analyzed apoptosisrelated
      genes is observed in all groups of leukemia. In most groups of leukemia being
      analyzed, BCL-2 up-regulation level is superior to that of BAX. Prominent MYC up
      regulation is observed in B-lymphoblastic leukemia/lymphoma, non-Hodgkin's
      lymphoma, and T-lymphoblastic leukemia/lymphoma groups. In
      myelodysplastic/myeloproliferative neoplasms, the striking up-regulation of Fas-1
      and P38MAPK is evident. Practically all the groups of leukemia are characterized
      by stable high ratios of P53 up-regulation. CONCLUSION: In Ukrainian patients, up
      regulation of six analyzed apoptosis-related genes is observed practically in all
      types of malignant diseases of hematopoietic and lymphoid tissues under study.
      Microarray-based analysis of these samples would be of great importance in terms
      of elucidating genomic interactions in leukemias and their possible association
      with ionizing radiation.

PMID- 21716209
TI  - Photolon enhancement of ultrasound cytotoxicity.
AB  - OBJECTIVE: To evaluate the impact of Photolon on cytostatic and cytotoxic effects
      of therapeutic range ultrasound in C6 glioma cells. METHODS: C6 glioma cells in
      suspension or monolayer cell culture were exposed to ultrasound (880 kHz, 0.2-0.7
      W/cm2) in the presence or absence of Photolon at the concentration of 1 MUg/ml in
      the culture medium, and then cell viability was evaluated. RESULTS: Photolon
      increased the cytotoxic effect of ultrasound by 1.5-2.3-fold but had no effect on
      its cytostatic activity. CONCLUSION: Photolon produces a pronounced
      sonosensitizing effect on glioma C6 cells and is a promising drug for sonodynamic
      treatment of malignant tumors.

PMID- 21716210
TI  - Non-Hodgkin's lymphoma of nasopharynx diagnosed during pregnancy (a case from
      practice).
AB  - The article presents the case of 32 years old woman with non-Hodgkin's lymphoma
      of the nasopharynx who received the anticancer treatment at 21-26 weeks of
      pregnancy (20 courses of radiation in dose of 40 Gy on the right half of the
      nasopharynx). The pregnancy was performed by cesarean section at the term of 32
      weeks, and a healthy girl was born. Timely diagnosis and correct treatment of non
      Hodgkin's lymphoma give the woman a chance to have a healthy child.

PMID- 21716211
TI  - [Laparoscopic surgery in regions: problems and ways of development].
AB  - The modern state of laparoscopic surgery in northern regions (Komi republic,
      Murmansk, Arkhangelsk and Vologda regions) of Russian Federation was surveyed
      according to the reports of 1998-2007 and 2009 years. Thus, the investigation
      revealed, that not more than 30% of general surgeons are handle laparoscopic
      technique. Laparoscopic procedures comprise about 20% of all abdominal operations
      in the surveyed regions. Statictically significant differences in the use of
      laparoscopic surgery were revealed between the regions (p<0,001). In 2009
      laparoscopically treated were: 82-98,5% cases of chronic calculous cholecystitis;
      37,5-70,3% cases of the acute calculous cholecystitis; 1,0-10,7% of the acute
      appendicitis and 0,5-7,8% of patients with perforated ulcer. Nevertheless, the
      increase of the laparoscopic share is statistically expected within 5 next years.

PMID- 21716212
TI  - [Complications after reconstructive implantation of silicone endoprostheses in
      patients with breast cancer].
AB  - Radical mastectomy, though is considered to be the main method of the breast
      cancer treatment, influences the physical and psychological rehabilitation of
      patients extremely negatively. Reconstructive silicone endoprosthesing alternates
      radical mastectomy. Complications of the procedure analysed using the experience
      of 120 women with breast cancer. The on-time detection of complications
      drastically improves long-term aesthetic results.

PMID- 21716213
TI  - [The virtual modeling of the robotic-assisted operations in abdominal surgery].
AB  - The experience of single institution of 43 robotic-assisted operations in the
      abdomen and retroperitoneal space has been analyzed. The problem of port
      placement conditioned the preoperative computed 3D-modelling of the operative
      course. The procedure allowed to optimize the movements of the robotic
      manipulators, decrease the risk of organ injury and overall incidence of intra-
      an postoperative complications.

PMID- 21716214
TI  - [The prognostic value of tumor cells blood circulation after liver surgery for
      cancer lesions].
AB  - The study aimed to prove the prognostic meaning of micrometastases blood
      circulation during liver resections for cancer lesions. 33 patients took part in
      the study. Circulating micrometastases were detected in blood using
      immunocytological method with pancytoceratine antibodies KL-1 and CAM 5.2. The
      majority of patients had colon cancer liver metastases (72,7%). Blood was sampled
      once in 8 patients, the rest 25 patients had double sampling: before and after
      liver mobilization. Patients with multiple liver metastases demonstrated tumor
      cells circulation more often. Of 58 tests, 25 were positive for tumor cells. 3
      year survival in those patients was 45,7 +/- 13,1%, 5-year survival was 24,4 +/-
      13,3%. Survival rates for patients with no circulating tumor cells detected were
      significantly higher.

PMID- 21716215
TI  - [Relaparotomy and laparostomy in treatment of early postoperative complications].
AB  - The cause-and-effect analysis of early (within 3 weeks after the initial surgery)
      relaparotomy was made, using the experience of 5286 laparotomized patients, of
      whom 82 (1,55%) had relaparotomy. The main reason of intraabdominal complications
      was the initial generalized peritonitis in emergency patients (85,4%). In
      comparison with data of 30 years prescription, the portion of postoperative
      peritonitis and bleeding had increased, though the number of eventrations and
      postoperative ileus, on the contrary, decreased. The introduction of laparoscopy
      eliminated the necessity of diagnostic relaparotomies. The mortality rate after
      the repeated surgery had decreased from 38,0% to 30,5%.

PMID- 21716216
TI  - [Methods of intraductal pancreatic hypertension elimination].
AB  - The study is devoted to the surgical treatment of benign pancreatic cysts.
      Results of the internal drainage of pancreatic duct ul system in 76 patients were
      analyzed. Pancreaticoenterostomy combined with partial pancreatic resection in 21
      cases, was performed in 53 patients. The rest 23 patients required no enterostomy
      of the main pancreatic duct. The lateral pancreaticojejunostomy was performed in
      48 patients, of whom 32 patients had an original reconstructive circulation of
      the intestinal loop applied. By the width of the pancreatic duct less then 5 mm,
      the original method of resection of the front surface of the pancreas was applied
      (n=5). The bilateral pancreaticojejunostomy was performed in 3 patients with the
      pancreatic duct width less then 5 mm and diastasis of the latter. There was no
      postoperative lethality; complicated postoperative period required reoperation in
      5,3%. Long-term results were considered good in 74,6%, satisfactory in 16,4% and
      unsatisfactory in 9% of patients.

PMID- 21716217
TI  - [Optimization of preoperative preparation of patients with acute intestinal
      obstruction].
AB  - Water and electrolyte imbalance is considered to be the mainstay of preoperative
      treatment of patients with acute intestinal obstruction. The correct preoperative
      preparation defines the anaesthesia course, which requires the team work of
      surgeon and aneasthesiologist. The benefits of such an approach is confirmed by
      the retrospective analysis of 84 case histories, operated on the reason of the
      acute intestinal obstruction. The rational combination of colloid and crystalloid
      solutions was jointly selected, which allowed to decrease the need of vasopressor
      use and minimized the ICU and overall hospital stay.

PMID- 21716218
TI  - [Low-temperature sterilization for the surgical infection prophylaxis].
AB  - The comparative characteristic of the accepted methods of low-temperature
      sterilization of medical equipment is given. Special attention is devoted to the
      surgical infection prophylaxis. The efficacy, expediency and safety of gas
      sterilization with ethilenoxide is proved. Plasmic methods of sterilization is
      recommended for use together with other methods of low-temperature sterilization.

PMID- 21716219
TI  - [Long-term follow-up results of carotid endarterectomy in patients with carotid
      stenosis and transient monocular blindness].
AB  - The study aimed to prove the efficacy of carotid endarterectomy in patients with
      transient monocular blindness caused by carotid arterial stenosis. 31 patients,
      aged 45-80 years, were included in the study. All patients were divided in 2
      groups: 16 patients from the first group had classic carotid endarterectomy with
      synthetic patch; 15 patients from the second group were treated conservatively.
      All operated patients had no stroke or transient ischemic attack and were spared
      from amaurosis attacks and even showed certain vision sharpness improvement.
      Whereas the majority of patients from the second group showed the recurrence of
      the amaurosis fugax attacks after the treatment. Carotid endarterectomy
      significantly improves the condition of an eye and prevents brain ischemia in
      patients with transient monocular blindness caused by carotid arterial stenosis.

PMID- 21716220
TI  - [Treatment of chronic critical ischemia by neuroischemic form of the diabetic
      foot syndrome].
AB  - Treatment results of 203 patients with critical ischemia by neuroischemic form of
      the diabetic foot sindrome were analyzed. 45 patients had open, endovascular or
      hybrid vascular reconstructions. The method was decised basing on the results of
      angiographic studies. The support function was saved in 34 (75,6%) cases of 45
      operated patients. Revascularization proved to be an effective and reasonable
      method of surgical intervention by critical ischemia caused by the neuroischemic
      form of the diabetic foot syndrome.

PMID- 21716221
TI  - [Structural and clinical characteristics of elderly and senile patients'
      treatment in regional surgical hospital].
AB  - Treatment results of 1219 patients of elderly and senile age, hospitalized in
      surgical departments of Turkestan during 2001-2008 were analyzed. Demographic
      characteristics, spectrum of profile pathology as well as concurrent diseases
      were given. Operative activity and average hospital stay, hospital lethality and
      complication rates were defined.

PMID- 21716222
TI  - [Prognostic factors of the immediate results of surgical treatment of organic
      hyperinsulinism].
AB  - The clinic obtains the experience of treatment of 245 patients with organic
      hyperinsulinism. The main goal of the treatment of that category of patients is
      an improvement of immediate results of surgical treatment which leads to the
      decrease in mortality level. Authors set the diagnostic and intra- and
      postoperative treatment algorithm, as well as the major prognostic factors of
      postoperative morbidity rates. The use of the algorithm allowed the 1,5 decrease
      in postoperative morbidity and twice decreased the lethality rate.

PMID- 21716223
TI  - [Antioxidant protection as a component of anesthetic management cancer patients].

PMID- 21716224
TI  - [The attempt of clinical classification of the complicated diabetic foot
      syndrome].
AB  - The experience of surgical treatment of 1532 patients with the complicated forms
      of diabetic foot syndrome (DFS) was analyzed. The original clinical
      classification of the complicated DFS was suggested. The classification
      considered the clinical form (symbol "C"), anatomic localization (symbol "Z") and
      etiology (symbol "E"). The classification allows to define surgical tactics
      depending on concrete complications of the DFS, frames conditions for the
      unification and uniform registration of the form and severity of the disease and
      volume of the surgical treatment.

PMID- 21716225
TI  - [Single-stage surgical treatment of the ascending aortic aneurism with dissection
      and coarctation].

PMID- 21716226
TI  - [Sparing surgical treatment of atherosclerotic aneurysms of the splenic artery,
      complicated by infarctions spleen].

PMID- 21716227
TI  - [The effective double high-frequency aquathermodestruction of recurrent tongue
      cancer in senile patient].

PMID- 21716228
TI  - [Mediso-organizational principles of orthopedic stomatological care rendering to
      patients with postoperative maxillofacial defects].
AB  - Complex research in which result key problems are revealed is done and the medico
      organizational substantiation is given modern principles of rendering of the
      orthopedic care to the patients with maxillofacial defects.

PMID- 21716229
TI  - [Possibilities evaluation of organization and delivery of stomatological help to
      children in need of complex maxillofacial prosthetics].
AB  - The article is devoted to the analysis of conditions of the organization of
      maxillofacial prosthetic help for children in 32 of 83 administrative regions of
      Russian Federation. The investigation was carried out in 2006. The materials of
      the investigation include the opinions of 72 management leaders of stomatological
      organizations. Results show the problems of treatment of children with complex
      difficulties of maxillofacial prosthetic help such as affability of treatment,
      integrations with other specialists, provide with personal, organization of
      treatment, and so on.

PMID- 21716230
TI  - [Stomatological help delivery perfection for patients with hematological
      problems].
AB  - Complex examination of dentistry status of the hematologic patients organized in
      condition of many profile hospitals. From 35 examined light degree of gravity of
      hemophilia A was revealed in 9 (25,7%) patients, average - in 11 (31,4%), heavy -
      in 15 (42,9%). Undertaking, complex integrated action within the framework of
      primary preventive maintenance of oral cavities in patients with hemophilia have
      allowed for two years to perfect of the dentistry status: reduce average hygienic
      index on 12,6%, index PMA on 15,5%, intensities of caries on 8,1% in the absence
      for this period of the development of the complicated forms of caries.

PMID- 21716231
TI  - [School stomatology condition in some regions of Russia].
AB  - Representative for the whole country study on school stomatology condition was
      performed in 9 regions of Russia. There were received data about the functioning
      of school stomatological rooms in 7165 schools including 3230 rural schools in
      which 1 606 138 children studied from which 33% were primaries. Several problems
      were disclosed in school dentistry system functioning including absence of
      unified licensing, manpower shortage, absence of stomatological rooms in new
      schools, re-equipment of earlier existed stomatological rooms by school
      administration decision, not allotment of dental hygienist into functioning.
      Necessity of school dentistry functioning reorganization into the side of
      stomatological diseases prevention was underlined.

PMID- 21716232
TI  - [Preventive orientation in caries treatment].
AB  - Based upon the analysis of 310 dental status assessment forms from 5 regions of
      Russia there were disclosed data on oral hygiene index, oral hygiene education,
      controllable cleaning procedure, professional hygiene, recommendations to clean
      oral cavity, regimen of nutrition and secondary visit terms. It was established
      that delivered treatment not in the fool corresponded with the protocol of
      patient treatment "Dental Caries" confirmed by Russian Deputy Minister of Health
      and Social Care 17 October 2006.

PMID- 21716233
TI  - [Analysis of the inhibitory capacity against bacterial growth of several
      materials of dental use. Preliminar].
AB  - Dental plaque is one of the reasons for odontogenic infection. Although multiple
      bacteria are involved in these processes, A.actinomycetemcomitans and S.mutans
      are considered directly responsible for localized aggressive periodontitis and
      caries respectively. On the other hand, it seems clear that the oral flora
      utilizes especially not well polished surfaces or without bacteriastatic capacity
      in order to obtain better adhesion. Based on those facts we expect to prove the
      inhibitory capacity "in vitro" of some materials used for teeth restoration and
      for the cementation of accessories against one common bacterium in the human
      flora and two pathogenic bacteria of the oral cavity. We prepared, following the
      manufacturer's instructions, 18 discs for each one of the materials used in the
      study (2 composites and 2 ionomeros of glass). 6 discs of each material are
      incubated with A. actinomycetemcomitans, S. mutans and E. coli. 3 of them are
      incubated directly on the discs and the other 3 are incubated previously in an
      artificial saliva for 24 days. From the results, should be highlighted that only
      one of the materials demonstrated inhibitory capacity against A.
      actinomycetemcomitans and E. coli. None of them demonstrated inhibitory capacity
      against S. mutans.

PMID- 21716234
TI  - [PCR "real time" to analyze the quantitative and qualitative relations microbiota
      of periodontal pockets].
AB  - The introduction of a broad medical practice PCR "real time" is just beginning
      and dentistry is no exception. Modern molecular genetic methods provide numerous
      opportunities for diagnosis, assessment and prediction in patients with
      inflammatory periodontal diseases. Early and accurate diagnosis can allow in the
      future reduce the incidence of periodontitis and the progression of its course.

PMID- 21716235
TI  - [Clinical-lab efficacy assessment of finishing strips with different abrasiveness
      degree].
AB  - Research is aimed at studying the efficacy and characteristics of various
      finishing strips. The data on the finishing strips line were classified and
      analyzed. The efficacy assessment was based on clinical study and scanning
      electronic microscopy. Various types of finishing strips were identified to have
      different efficacy degree which affects the clinical and functional guides.

PMID- 21716236
TI  - [New digital method of small salivary glands sialometry].
AB  - The authors suggested new digital method of small salivary glands (SSG)
      sialometry. The proposed method foresee SSG functional activity determination by
      SSG smears making upon transparent celluloid film painted on one side by water
      soluble dye and further transfer (scanning) of the print into digital picture
      with the possibility of its further processing and storage upon digital carrier.

PMID- 21716237
TI  - [Quantitative detection of periodontopatogenic microflora in periodontosis and
      healthy control].
AB  - Mouth human populated set of microorganisms that are in dynamic equilibrium and
      forming microbiocaenosis. In a situation where this balance is disturbed, there
      is a "activation" of pathogens, including those that lead to the development of
      inflammatory periodontal diseases. Quantifying the relation parodontopatogenov in
      this material may be an important diagnostic tool, but data on the profile of
      individual microbiota subbiotopov mouth so far very little. In this study, we
      quantified the six pathogenic representatives of the periodontal pocket
      microbiota in health and periodontitis. Found that when disease development
      relationship pathogenic representatives of periodontal pocket microbiota varies
      considerably.

PMID- 21716238
TI  - [Characteristics of microbiocenosis of gingival pocket in patients with chronic
      generalized periodontitis].
AB  - As a result of examination of 56 patients with chronic generalized periodontitis
      (CGP) of a moderate severity and a severe form of the disease, microflora from
      gingival pocket in patients which severe form of CGP was established to have
      higher specific weight in index of dissemination of strains such as
      Staphylococcus aureus, Streptococcus pyogencs, Enterococcus, Corynebacterium
      spp., anaerobic bacteria. Strains from patients with a severe form of CGP were
      characterized by a higher level of expression of the factors of pathogenicity and
      persistence. Associations of streptococci and staphylococci which the
      representatives of anaerobic flora such as Bacteroides, Fusobacterium,
      Prevotella, Clostridium, Peptostreptococcus were more often revealed in patients
      with a severe form of CGP. Fact of microbial translocation from the gingival
      pocket was established: from the blood of the patients with CGP of a severe form,
      strains-translocants were cultivated by 4 times more frequently than from the
      patients with CGP of a moderate severity.

PMID- 21716239
TI  - [A long-term 3D cast model analysis focusing bone-borne vs. tooth-borne SARME].
AB  - This retrospective study evaluated 34 patients pre- and ~20.5 months post
      expansion 3D scanned cast models with tooth-borne (TV, n1=16) and bone-borne (BB,
      n2=18) devices. Measurements were performed for transverse skeletal/dental
      maxillary widening, dental tipping and dental attachment loss. RESULTS: T-Test in
      long-term effects: BB: bigger, symmetric transverse widening along the dental
      arch; bigger attachment loss in the frontal teeth, canines, 2nd premolars.
      molars; bigger dental tipping in the canines and 2nd molars; TV: asymmetric
      transverse widening along the dental arch; bigger attachment loss in the 1st
      premolars: bigger dental tipping in the premolars and 1st molars. CONCLUSION: BB
      should be used whenever bigger transverse maxillary expansion is required, new
      distractor designs may reduce segmental inclination and initial expansion
      asymmetries, consequently, eliminating the related attachment loss from secondary
      orthodontic tooth movements for arch alignment. TV devices showed minor expansion
      with good periodontal attachment, yet attachment loss in the first premolars must
      be critically seen in bigger expansion distances.

PMID- 21716240
TI  - [Surgical aspects of clinical use of short surface porous dental implants].
AB  - Surgical aspects of clinical use of 155 short surface porous dental implants were
      analyzed in the work. It was disclosed that surgical preparation of oral cavity
      for making prosthetics with the help of implants of the 5, 7 and 9 mm long was
      easy and appropriate method of treatment both for the doctor and the patient. It
      was proved that short surface porous dental implants placing provided significant
      reduction of the closest postoperative complications and statistically
      significant increase of summary clinical efficacy in comparison with the use of
      short screw implants and bone-plastic operations with further installation of
      screw implants of usual size.

PMID- 21716241
TI  - [Experience in diagnostics and treatment of patients with odontogenous maxillary
      sinusitis].
AB  - 210 sick dontogenous maxillary sinusitis were studied. To 150 patients surgical
      treatment with use of a method of a osteo-plastic sinusotomy of a genyantrum is
      lead. Patients have been taken on a dispensary observation. According to the lead
      postoperative computer tomography of additional sinuses of a nose in two
      projections, and also ortopantomography, rentgenographies of sinuses in semiaxial
      projection, the pneumatization of the operated genyantrums has not been
      disturbed, the osteal forward wall has been kept on all extent, was absent
      retraction soft tissues of infraorbital area, that as a whole speaks about
      efficiency and not so traumaticaly the lead surgical treatment. The offered way
      of surgical treatment promotes to the greatest degree to conservation of anatomic
      structures of maxillofacial area, possessing the least traumatism in comparison
      with other ways. This technique is simple, effective and does not demand
      application of the expensive equipment.

PMID- 21716242
TI  - [The mechanical models of the physiology of teeth].
AB  - Based on the universal laws of mechanics and physical chemistry, physiology build
      mechanical models of teeth, which allowed to explain the role of mastication in
      the mechanism of demineralization and remineralization of hard tissues of teeth
      and asymmetry of erasing their working surfaces. In the process of chewing
      capillary and baric effects contribute to changes in calcium and phosphorus on
      the working side of the tooth, reaching 30% for any chemical composition of food.
      Erasing the working surfaces of lower teeth contributes to their specific role in
      the mechanical and chemical mechanisms of degradation of food due to the mobility
      of the mandible.

PMID- 21716243
TI  - [Importance of submandibular salivary glands for organism].
AB  - Based upon analysis of postoperative morbidity the authors concluded that
      salivary glands extirpation led to considerably often development of different
      gastrointestinal tract diseases in comparison with other operative interventions.
      The most often (62%) these diseases appeared in patients with submandibular
      salivary gland removal in anamnesis and rarer (21%) - with parotid salivary gland
      removal. So it could be claimed that salivary glands were an important
      constituent part of digestive system. Salivary glands removal was only proper in
      case of impossibility of carrying organ preserving operative intervention.

PMID- 21716244
TI  - [Mental health of the world population: epidemiological aspects (the analysis of
      foreign research results for 2000-2010)].
AB  - Modern approaches to studying prevalence of a mental pathology and the results
      received during 2000-2010 are analyzed according to a condition of mental health
      of the population of separate regions and countries of the world. Information
      sources were databases of the WHO, a database of the United States National
      Library of Medicine "PubMed", archives of publications of leading foreign medical
      magazines in the field of mental health. The growth of prevalence and incidence
      of mental illnesses, especially depressive and anxiety disorders, with the
      corresponding increasing burden of mental disorders worldwide is observed. To
      obtain reliable results, modern schemes of epidemiological studies should be
      realized with the account of social-cultural level of the population, adaptation
      of diagnostic tools, qualitative preparation and training of the personnel and
      with the precise use of statistical criteria and requirements to the selection
      and analysis of research information.

PMID- 21716245
TI  - [Morphological, clinical, diagnostic features and the treatment of patients with
      giant brain aneurisms].
AB  - Retrospective analysis of treatment outcomes of 89 patients with GIAs, treated in
      Sklifosovsky Emergency Care Institute from 01.01.1992 till 30.11.2010, was
      performed. 67 patients were operated on, among them open surgery was conducted
      for 49 patients, endovascular embolisation - 18 patients. Severity of patients'
      condition was assessed according to Hunt - Hess (H-H) scale, level of
      consciousness - Glasgow Coma Scale (GCS), treatment outcomes - Glasgow Outcomes
      Scale (GOS). Hemorrhage due to GIA rupture was seen at u 64 (72,0%) patients,
      mass lesion signs - at 18 (20,2%), embolic events - at 3 (3,4%) and GIA without
      any symptoms - at 4 (4,4%) patients. Good and excellent outcomes were at 79,1%
      operated patients, total lethality among operated patients was 13,4%. Lethality
      among non-operated patients was 47,4%. Conservative treatment of patients with
      GIAs has low perspectives. Open and endovascular operative interventions are the
      high-risk surgery but they allow decreasing the lethality and morbidity rate
      among these patients compared with conservative treatment.

PMID- 21716246
TI  - [Manifesting schizophrenic attacks in female adolescents].
AB  - Authors have analyzed pre-manifesting symptoms as well as initial and manifesting
      stages of the disease on the basis of examination of 70 patients, aged 15-17
      years. Schizoid and psychastenic types dominated in the premorbid structure of
      personality. The following variants of the initial stage were singled out:
      affective, psychopathic-like, with overvalued disorders, neurotic-like, with the
      predomination of simplex-syndrome, clinically polymorphic. Manifesting
      schizophrenic attacks in female adolescents were determined by affective
      delusive, hallucinatory-delusive, oneiroid-catatonic and polymorphic syndromes.
      The attack-like course was found in most of cases. The typological similarity of
      psychotic states studied with those of adult schizophrenic patients was noted.

PMID- 21716247
TI  - [Efficacy and practicability of using intravenous human immunoglobulin in the
      pathogenetic treatment of patients with generalized myasthenia].
AB  - The treatment with immunoglobulin (IgG) has led to the clinical improvement in
      all 12 patients with generalized myasthenia and practically has not caused any
      side-effects. The highest efficacy was seen in patients with a threat of or
      developed mixed crisis who received high doses of IgG (0,4-0,5 g per one kg of
      body mass) in the course of 3-5 intravenous drop introductions administered along
      with basic treatment with glucocorticoid and immunosuppressive drugs. In patients
      who received IgG once in smaller doses (0,2-0,3 g per one kg of body mass) to
      stabilize the disease course or to hasten recovery from the exacerbation, the
      clinical effect was similar though less prolonged. The treatment course with IgG
      stopped myasthenic crises in all cases. The clinical efficacy of IgG was not
      correlated with anti-acetylcholine receptor antibodies.

PMID- 21716248
TI  - [Effect of the direct electric stimulation of the spinal cord in the treatment of
      neurologic complications of cervical osteochondrosis].
AB  - The results of the treatment of 92 patients with neurologic complications of
      cervical osteochondrosis (26 patients with isolated persistent lesions of roots
      C4-C7 and 66 patients with the combination of root syndromes and cervical
      myelopathy) are presented. The combination of direct electric stimulation of the
      spinal cord with different methods of surgical treatment was used. The efficacy
      of treatment was assessed with the scale for measuring severity of neurologic
      complications of cervical osteochondrosis and by electromyographic data before
      treatment and 1 and 6 months after the surgery. The significantly higher (p<0,05)
      effect of surgical treatment in the combination with direct electric stimulation
      of the spinal cord was shown.

PMID- 21716249
TI  - [The experience of using the atypical antipsychotic sertindole in psychiatric
      inpatient clinics in Russia].
AB  - One hundred and fifty psychiatrists from 61 clinics of 30 cities located in 8
      regions of the Russian Federation took part in the study. The study included 896
      patients treated with sertindole. The duration of illness was from 1 month to 50
      years (mean 9,55 +/- 8,21), a number of previous relapses varied from 0 to 20 and
      more (mean 5,79 +/- 6,68). Each patient was followed up for 6 weeks. Patient's
      state was assessed clinically and with the CGI. The statistically significant
      improvement was seen from the first week of treatment and the percentage of
      patients with marked mental disorders was constantly decreased from the first to
      the 6th week. It has been concluded that sertindole is an effective drug for
      stopping psychotic symptoms in the real practice of treatment of schizophrenic
      patients. It is well-tolerated and allows to reduce a number of concurrent drugs
      used for treatment.

PMID- 21716250
TI  - [Efficacy of treatment of focal forms of epilepsy in children with antiepileptic
      drugs of different generations].
AB  - An aim was to study the efficacy of different groups of antiepileptic drugs in
      the treatment of focal symptomatic (or probably symptomatic) epilepsy in
      children. The study included 96 patients, aged from 1 month to 17 years, 55 boys
      and 41 girls. They were stratified into three groups by drug type: group 1 (34
      patients) was treated with phenobarbital, group 2 (31 patients) received
      topiramate and group 3 (31 patients) received lamotrigine. It has been shown that
      antiepileptic drugs of the new generation have higher efficacy with regard to
      focal forms of epilepsy in children compared to phenobarbital. However
      therapeutic effect, especially regarding seizure frequency, was specific for each
      drug.

PMID- 21716251
TI  - [Focal neuropathies: new possibilities for pharmacological treatment].
AB  - An open randomized trial of 58 patients with focal neuropathies of upper
      extremities has compared the efficacy of neyromidin (ipidacrinum) used in
      intramuscular injections and by the introduction of local injection perineural
      therapy. Both methods were combined with the following electroneurostimulation at
      the peak of drug action (30 min after the injection). The efficacy of treatment
      was assessed 14 days and 1 month after the end of treatment course by specific
      questionnaires and scales and an electroneuromyographic study. The data obtained
      indicate the efficacy of neyromidin in the treatment of patients with focal
      neuropathies of upper extremities. The introduction of the drug using local
      injection perineural therapy has demonstrated significantly better results.

PMID- 21716252
TI  - [The association between the NRG1 gene polymorphism and cognitive functions in
      patients with schizophrenia and healthy controls].
AB  - NRG1 is a strong candidate for schizophrenia though its role in the pathogenesis
      of the disease remains unknown. One of the approaches to study mechanisms
      underlying the association between NRG1 and schizophrenia is to investigate the
      association between a gene and an endophenotype of schizophrenia, e.g., cognitive
      dysfunctions. Authors looked for the association of 478B14-848 i 420M9-1395
      microsatellites with semantic verbal fluency, working and episodic memory in 338
      patents with schizophrenia, 162 their unaffected relatives and 316 healthy
      controls from the Russian population. It was found associations between allele 0
      at 478B14-848 (220 bp) and long-term episodic memory and between allele 0 at
      420M9-1395 (274 bp) and short-term memory in schizophrenic patients. The
      frequency of homozygotes for 420M9-1395 was higher in the group of patients as
      compared to controls. In conclusion, the risk allele 0 at 420M9-1395 is
      associated with the short-term memory deficit while allele 0 at 478B14-848 is
      protective for long-term memory deficits.

PMID- 21716255
TI  - Cyclooxygenase-2-dependent phosphorylation of the pro-apoptotic protein Bad
      inhibits tonicity-induced apoptosis in renal medullary cells.
AB  - During antidiuresis, cell survival in the renal medulla requires cyclooxygenase-2
      (COX-2) activity. We have recently found that prostaglandin E2 (PGE2) promotes
      cell survival by phosphorylation and, hence, inactivation of the pro-apoptotic
      protein Bad during hypertonic stress in Madin-Darby canine kidney (MDCK) cells in
      vitro. Here we determine the role of COX-2-derived PGE(2) on phosphorylation of
      Bad and medullary apoptosis in vivo using COX-2-deficient mice. Both wild-type
      and COX-2-knockout mice constitutively expressed Bad in tubular epithelial cells
      of the renal medulla. Dehydration caused a robust increase in papillary COX-2
      expression, PGE2 excretion, and Bad phosphorylation in wild-type, but not in the
      knockout mice. The abundance of cleaved caspase-3, a marker of apoptosis, was
      significantly higher in papillary homogenates, especially in tubular epithelial
      cells of the knockout mice. Knockdown of Bad in MDCK cells decreased tonicity
      induced caspase-3 activation. Furthermore, the addition of PGE2 to cells with
      knockdown of Bad had no effect on caspase-3 activation; however, PGE2 caused
      phosphorylation of Bad and substantially improved cell survival in mock
      transfected cells. Thus, tonicity-induced COX-2 expression and PGE2 synthesis in
      the renal medulla entails phosphorylation and inactivation of the pro-apoptotic
      protein Bad, thereby counteracting apoptosis in renal medullary epithelial cells.

PMID- 21716256
TI  - Unilateral anomalies of kidney development: why is left not right?
AB  - Abnormal renal development results in congenital anomalies of the kidney and
      urinary tract. As many studies suggest that renal malformations are more often
      found on the left side, a meta-analysis was performed on the distribution of five
      different unilateral anomalies: multicystic dysplastic kidney, renal
      agenesis/aplasia, renal ectopia, pelviureteral junction obstruction, and non
      obstructive non-refluxing megaureter. Of these anomalies, the left side was
      affected in 53%, 57%, 56.9%, 63.2%, and 62.5% of patients, respectively,
      significantly different when compared with an anticipated 50% of left-sided
      anomalies. An exception to this left-side predominance was found in females with
      combined genital anomalies and unilateral renal agenesis that commonly present on
      the right side. The exact mechanisms leading to these lateralizations remain to
      be determined but may involve vascular development, differential gene expression,
      or susceptibility to environmental factors such as hypoxia. This remains largely
      speculative, however, illustrating our limited knowledge of embryogenesis in
      general and nephrogenesis in particular.

PMID- 21716257
TI  - Slc26a11, a chloride transporter, localizes with the vacuolar H(+)-ATPase of A
      intercalated cells of the kidney.
AB  - Chloride has an important role in regulating vacuolar H(+)-ATPase activity across
      specialized cellular and intracellular membranes. In the kidney, vacuolar H(+)
      ATPase is expressed on the apical membrane of acid-secreting A-type intercalated
      cells in the collecting duct where it has an essential role in acid secretion and
      systemic acid base homeostasis. Here, we report the identification of a chloride
      transporter, which co-localizes with and regulates the activity of plasma
      membrane H(+)-ATPase in the kidney collecting duct. Immunoblotting and
      immunofluorescent labeling identified Slc26a11 (~72 kDa), expressed in a subset
      of cells in the collecting duct. On the basis of double-immunofluorescent
      labeling with AQP2 and identical co-localization with H(+)-ATPase, cells
      expressing Slc26a11 were deemed to be distinct from principal cells and were
      found to be intercalated cells. Functional studies in transiently transfected
      COS7 cells indicated that Slc26a11 (designated as kidney brain anion transporter
      (KBAT)) can transport chloride and increase the rate of acid extrusion by means
      of H(+)-ATPase. Thus, Slc26a11 is a partner of vacuolar H(+)-ATPase facilitating
      acid secretion in the collecting duct.

PMID- 21716258
TI  - Oliguria is an early predictor of higher mortality in critically ill patients.
AB  - Oliguria is a valuable marker of kidney function and a criterion for diagnosing
      and staging acute kidney injury (AKI). However, the utility of urine output as a
      specific metric for renal dysfunction is somewhat controversial. To study this
      issue further we tested whether urine output is a sensitive, specific, and early
      measure for diagnosing and staging AKI in 317 critically ill patients in a
      prospective observational study. Urine output was assessed every hour and serum
      creatinine every 12 to 24  h. The sensitivity and specificity of different
      definitions of oliguria for the diagnosis of AKI were compared with the Acute
      Kidney Injury Network serum creatinine criterion. The incidence of AKI increased
      from 24%, based solely on serum creatinine, to 52% by adding the urine output as
      a diagnostic criterion. Oliguric patients without a change in serum creatinine
      had an intensive care unit mortality rate (8.8%) significantly higher than
      patients without AKI (1.3%), and similar to oliguric patients with an increase in
      serum creatinine (10.4%). The diagnosis of AKI occurred earlier in oliguric than
      in non-oliguric patients. Oliguria of more than 12  h and oliguria of 3 or more
      episodes were associated with an increased mortality rate. Thus, urine output is
      a sensitive and early marker for AKI and is associated with adverse outcomes in
      intensive care unit patients.

PMID- 21716259
TI  - Platelet-derived growth factor receptor signaling activates pericyte
      myofibroblast transition in obstructive and post-ischemic kidney fibrosis.
AB  - Pericytes are the major source of scar-producing myofibroblasts following kidney
      injury; however, the mechanisms of this transition are unclear. To clarify this,
      we examined Collagen 1 (alpha1)-green fluorescent protein (GFP) reporter mice
      (pericytes and myofibroblasts express GFP) following ureteral obstruction or
      ischemia-reperfusion injury and focused on the role of platelet-derived growth
      factor (PDGF)-receptor (PDGFR) signaling in these two different injury models.
      Pericyte proliferation was noted after injury with reactivation of alpha-smooth
      muscle actin expression, a marker of the myofibroblast phenotype. PDGF expression
      increased in injured tubules, endothelium, and macrophages after injury, whereas
      PDGFR subunits alpha and beta were expressed exclusively in interstitial GFP
      labeled pericytes and myofibroblasts. When PDGFRalpha or PDGFRbeta activation was
      inhibited by receptor-specific antibody following injury, proliferation and
      differentiation of pericytes decreased. The antibodies also blunted the injury
      induced transcription of PDGF, transforming growth factor beta1, and chemokine
      CCL2. They also reduced macrophage infiltration and fibrosis. Imatinib, a PDGFR
      tyrosine kinase inhibitor, attenuated pericyte proliferation and kidney fibrosis
      in both fibrogenic models. Thus, PDGFR signaling is involved in pericyte
      activation, proliferation, and differentiation into myofibroblasts during
      progressive kidney injury. Hence, pericytes may be a novel target to prevent
      kidney fibrosis by means of PDGFR signaling blockade.

PMID- 21716260
TI  - Short-term vitamin D receptor activation increases serum creatinine due to
      increased production with no effect on the glomerular filtration rate.
AB  - Vitamin D receptor activation has been associated with increased serum creatinine
      and reduced estimated glomerular filtration rates, raising concerns that its use
      may be detrimental to kidney function. Here we studied the effect of vitamin D
      receptor activation on serum creatinine, creatinine generation, and its
      clearance. We measured baseline serum creatinine and 24-h urine creatinine in 16
      patients with chronic kidney disease. The measurements were repeated every day
      for 7 days, during which time the patients received 2 MUg paricalcitol, an orally
      active vitamin D receptor activator, every morning. At 4 days after stopping the
      vitamin analog, measurements were continued for 3 days. Geometric mean
      parathyroid hormone levels decreased from 77 pg/ml at baseline to 43 pg/ml at the
      end of treatment and significantly rebounded to 87 pg/ml following paricalcitol
      withdrawal, thereby supporting the biological efficacy of the analog dose used.
      With this therapy, the serum creatinine significantly increased at a rate of
      0.010 mg/dl/day and urine creatinine at a rate of 17.6 mg/day. Creatinine and
      iothalamate clearances did not change, whereas urine albumin decreased
      insignificantly. Thus, short-term vitamin D receptor activation increases
      creatinine generation and serum creatinine, but it does not influence the
      glomerular filtration rate.

PMID- 21716261
TI  - Hydrogen sulfide inhibits the calcification and osteoblastic differentiation of
      vascular smooth muscle cells.
AB  - Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is involved
      in the pathogenesis of vascular calcification. Hydrogen sulfide (H(2)S) is a gas
      endogenously produced by cystathionine gamma-lyase in VSMC. Here we determined
      whether H(2)S plays a role in phosphate-induced osteoblastic transformation and
      mineralization of VSMC. Hydrogen sulfide was found to inhibit calcium deposition
      in the extracellular matrix and to suppress the induction of the genes involved
      in osteoblastic transformation of VSMC: alkaline phosphatase, osteocalcin, and
      Cbfa1. Moreover, phosphate uptake and phosphate-triggered upregulation of the
      sodium-dependent phosphate cotransporter (Pit-1) were also prevented by H(2)S.
      Reduction of endogenous production of H(2)S by inhibition of cystathionine gamma
      lyase activity resulted in increased osteoblastic transformation and
      mineralization. Low plasma levels of H(2)S, associated with decreased
      cystathionine gamma-lyase enzyme activity, were found in patients with chronic
      kidney disease receiving hemodialysis. Thus, H(2)S is a potent inhibitor of
      phosphate-induced calcification and osteoblastic differentiation of VSMC. This
      mechanism might contribute to accelerated vascular calcification in chronic
      kidney disease.

PMID- 21716262
TI  - Differential activity by polymorphic variants of a remote enhancer that supports
      galanin expression in the hypothalamus and amygdala: implications for obesity,
      depression and alcoholism.
AB  - The expression of the galanin gene (GAL) in the paraventricular nucleus (PVN) and
      in the amygdala of higher vertebrates suggests the requirement for highly
      conserved, but unidentified, regulatory sequences that are critical to allow the
      galanin gene to control alcohol and fat intake and modulate mood. We used
      comparative genomics to identify a highly conserved sequence that lay 42 kb 5' of
      the human GAL transcriptional start site that we called GAL5.1. GAL5.1 activated
      promoter activity in neurones of the PVN, arcuate nucleus and amygdala that also
      expressed the galanin peptide. Analysis in neuroblastoma cells demonstrated that
      GAL5.1 acted as an enhancer of promoter activity after PKC activation. GAL5.1
      contained two polymorphisms; rs2513280(C/G) and rs2513281(A/G), that occurred in
      two allelic combinations (GG or CA) where the dominant GG alelle occurred in 70
      83 % of the human population. Intriguingly, both SNPs were found to be in LD
      (R(2) of 0.687) with another SNP (rs2156464) previously associated with major
      depressive disorder (MDD). Recreation of these alleles in reporter constructs and
      subsequent magnetofection into primary rat hypothalamic neurones showed that the
      CA allele was 40 % less active than the GG allele. This is consistent with the
      hypothesis that the weaker allele may affect food and alcohol preference. The
      linkage of the SNPs analysed in this study with a SNP previously associated with
      MDD together with the functioning of GAL5.1 as a PVN and amygdala specific
      enhancer represent a significant advance in our ability to understand alcoholism,
      obesity and major depressive disorder.

PMID- 21716263
TI  - N-acetyl cysteine treatment rescues cognitive deficits induced by mitochondrial
      dysfunction in G72/G30 transgenic mice.
AB  - Genetic studies have implicated the evolutionary novel, anthropoid primate
      specific gene locus G72/G30 in psychiatric diseases. This gene encodes the
      protein LG72 that has been discussed to function as a putative activator of the
      peroxisomal enzyme D-amino-acid-oxidase (DAO) and as a mitochondrial protein. We
      recently generated 'humanized' bacterial artificial chromosome transgenic mice
      (G72Tg) expressing G72 transcripts in cells throughout the brain. These mice
      exhibit several behavioral phenotypes related to psychiatric diseases. Here we
      show that G72Tg mice have a reduced activity of mitochondrial complex I, with a
      concomitantly increased production of reactive oxygen species. Affected neurons
      display deficits in short-term plasticity and an impaired capability to sustain
      synaptic activity. These deficits lead to an impairment in spatial memory, which
      can be rescued by pharmacological treatment with the glutathione precursor N
      acetyl cysteine. Our results implicate LG72-induced mitochondrial and synaptic
      defects as a possible pathomechanism of psychiatric disorders.

PMID- 21716264
TI  - Smoke extracts and nicotine, but not tobacco extracts, potentiate firing and
      burst activity of ventral tegmental area dopaminergic neurons in mice.
AB  - Nicotine prominently mediates the behavioral effects of tobacco consumption,
      either through smoking or when taking tobacco by snuff or chew. However, many
      studies question the exclusive role of nicotine in these effects. The use of
      preparations containing all the components of tobacco, such as tobacco and smoke
      extracts, may be more suitable than nicotine alone to investigate the behavioral
      effects of smoking and tobacco intake. In the present study, the
      electrophysiological effects of tobacco and smoke on ventral tegmental area
      dopaminergic (DA) neurons were examined in vivo in anesthetized wild-type (WT),
      beta2-nicotinic acetylcholine receptor (nAChR) knockout (beta2-/-), alpha4-/-,
      and alpha6-/- mice and compared with those of nicotine alone. In WT mice, smoke
      and nicotine had similar potentiating effects on DA cell activity, but the action
      of tobacco on neuronal firing was weak and often inhibitory. In particular,
      nicotine triggered strong bursting activity, whereas no bursting activity was
      observed after tobacco extract (ToE) administration. In beta2-/- mice, nicotine
      or extract elicited no modification of the firing patterns of DA cells,
      indicating that extract acts predominantly through nAChRs. The differences
      between DA cell activation profiles induced by tobacco and nicotine alone
      observed in WT persisted in alpha6-/- mice but not in alpha4-/- mice. These
      results would suggest that tobacco has lower addiction-generating properties
      compared with either nicotine alone or smoke. The weak activation and prominent
      inhibition obtained with ToEs suggest that tobacco contains compounds that
      counteract some of the activating effects of nicotine and promote inhibition on
      DA cell acting through alpha4beta2*-nAChRs. The nature of these compounds remains
      to be elucidated. It nevertheless confirms that nicotine is the main substance
      involved in the tobacco addiction-related activation of mesolimbic DA neurons.

PMID- 21716265
TI  - Biofilms can be dispersed by focusing the immune system on a common family of
      bacterial nucleoid-associated proteins.
AB  - Bacteria that cause chronic and/or recurrent diseases often rely on a biofilm
      lifestyle. The foundation of the biofilm structure is the extracellular polymeric
      substance (EPS) that acts as a barrier to both effectors of the immune system and
      antimicrobial agents. Recent work has highlighted extracellular DNA (eDNA) as a
      key component common to many pathogenic biofilms. Here, we show that the DNABII
      family of proteins, well known for their strong structural influences on
      intracellular DNA, was also critical for the integrity of the EPS matrix of
      biofilms that contain eDNA. In fact, antisera derived against a purified
      Escherichia coli DNABII family member rapidly disrupts the biofilm EPS formed by
      multiple human pathogens in vitro. In addition, when a member of this family of
      proteins was used as an immunogen in an animal model in which the bacteria had
      already formed a robust biofilm at the site of infection, the resultant targeted
      immune response strongly ameliorated this biofilm disease in vivo. Finally, this
      methodology to debulk the biofilm of EPS was shown to work synergistically with
      otherwise ineffective traditional anti-microbial approaches in vitro. We discuss
      the prospects for targeting DNABII family members as a potential universal
      strategy for treating biofilm diseases.

PMID- 21716266
TI  - Allergen challenge increases anandamide in bronchoalveolar fluid of patients with
      allergic asthma.

PMID- 21716267
TI  - Exposure to oral S-ketamine is unaffected by itraconazole but greatly increased
      by ticlopidine.
AB  - This study examined drug-drug interactions of oral S-ketamine with the cytochrome
      P450 (CYP) 2B6 inhibitor ticlopidine and the CYP3A inhibitor itraconazole. In
      this randomized, blinded, crossover study, 11 healthy volunteers ingested 0.2
      mg/kg S-ketamine after pretreatments with oral ticlopidine (250 mg twice daily),
      itraconazole (200 mg once daily), or placebo in 6-day treatment periods at
      intervals of 4 weeks. Ticlopidine treatment increased the mean area under the
      plasma concentration-time curve extrapolated to infinity (AUC(0-infinity)) of
      oral ketamine by 2.4-fold (P < 0.001), whereas itraconazole treatment did not
      increase the exposure to S-ketamine. The ratio of norketamine AUC(0-infinity) to
      ketamine AUC(0-infinity) was significantly decreased in the ticlopidine (P <
      0.001) and itraconazole phases (P = 0.006) as compared to placebo. In the
      ticlopidine and itraconazole phases, the areas under the effect-time curves (self
      reported drowsiness and performance) were significantly higher than those in the
      placebo phase (P < 0.05). The findings suggest that the dosage of S-ketamine
      should be reduced in patients receiving ticlopidine.

PMID- 21716268
TI  - Applications of translational bioinformatics in transplantation.

PMID- 21716269
TI  - Profile of serum bile acids in noncholestatic volunteers: gender-related
      differences in response to fenofibrate.
AB  - Fenofibrate belongs to the group of hypolipidemic fibrates that act as activators
      of the peroxisome proliferator-activated receptor-alpha (PPARalpha), which is a
      regulator of bile acid synthesis, metabolism, and transport. The present study
      aimed at evaluating the effects of fenofibrate on the circulating bile acid
      profile in humans. A study population of 200 healthy individuals comprising both
      genders completed a 3-week intervention with fenofibrate, and 17 bile acid
      species were measured in serum samples drawn before and after fenofibrate
      treatment. Fenofibrate caused significant reductions in levels of
      chenodeoxycholic (CDCA) (-26.4%), ursodeoxycholic (UDCA) (-30.5%), lithocholic
      (LCA) (-18.4%), deoxycholic (DCA) (-22.3%), and hyodeoxycholic (HDCA) (-19.2%)
      acids. A gender-related difference was observed in the responses of various bile
      acids, and the total bile acid concentration was significantly reduced only in
      men (-18.6%), whereas it remained almost unchanged in women (+0.36%). This
      difference suggests that fenofibrate would be more efficient at reducing bile
      acid toxicity in men than in women in cholestatic liver diseases.

PMID- 21716270
TI  - Management of infectious complications in solid-organ transplant recipients.

PMID- 21716271
TI  - Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome
      P450-2C19 (CYP2C19) genotype and clopidogrel therapy.

PMID- 21716272
TI  - Prediction of torsade de pointes from the QT interval: analysis of a case series
      of amisulpride overdoses.
AB  - Electrocardiograms (ECGs) from a case series of 86 amisulpride overdose events in
      66 patients were reviewed for abnormal QT intervals and torsade de pointes (TdP).
      Eight patients exhibited TdP. In this investigative case series, the magnitude of
      prolongation of the QT interval was a stronger predictor of TdP than the mere
      presence of a prolongation per se.

PMID- 21716273
TI  - Nonlinear pharmacokinetics of oral quinidine and verapamil in healthy subjects: a
      clinical microdosing study.
AB  - Microdosing studies are effective in enabling the early identification of the
      pharmacokinetic properties of compounds administered to humans. However, the
      nonlinearity of the pharmacokinetics between microdose and therapeutic dose,
      attributable to the saturation of metabolic enzymes and transporters, is a major
      concern. Verapamil and quinidine are good substrates of both the multidrug
      resistance 1 transporter (MDR1) and the cytochrome P450 (CYP) 3A4 enzyme
      (CYP3A4). We investigated their dose-dependent pharmacokinetics in healthy
      subjects. Four different doses of verapamil or quinidine were administered orally
      to each subject, and the plasma concentrations of the parent drugs and their
      major metabolites were measured. The dose-normalized area under the plasma
      concentration-time curve (AUC) values of quinidine and verapamil increased in a
      dose-dependent manner and were 2.6- and 2.3-fold higher, respectively, at the
      therapeutic dose than at microdose. These results suggest that the nonlinear
      pharmacokinetics of these drugs is caused mainly by the saturation of MDR1 and/or
      CYP3A4 in the small intestine.

PMID- 21716274
TI  - Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on
      active metabolite exposure and antiplatelet response in healthy subjects.
AB  - A double-blind crossover study was conducted in four CYP2C19 genotype-defined
      metabolizer groups to assess whether increase in clopidogrel dosing can overcome
      reduced pharmacodynamic response in CYP2C19 poor metabolizers (PMs). Ten healthy
      subjects in each of four metabolizer groups were randomized to a clopidogrel
      regimen of a 300-mg loading dose (LD) and a 75-mg/day maintenance dose (MD) for 4
      days followed by 600-mg LD and 150 mg/day MD, or vice versa. The exposure levels
      of clopidogrel's active metabolite H4 (clopi-H4) in PMs were 71% lower on the 75
      mg/day regimen and 64% lower on the 150-mg/day regimen than the corresponding
      exposure levels in extensive metabolizers (EMs). In PMs, the maximal platelet
      aggregation (MPA) induced by adenosine diphosphate (ADP) 5 umol/l was 10.5% lower
      on the 75-mg/day regimen and 7.9% lower on the 150-mg/day regimen than the
      corresponding values in EMs. PMs who were on the clopidogrel regimen of 600-mg
      LD/150 mg/day MD showed clopi-H4 exposure and MPA levels similar to those in EMs
      who were on the regimen of 300-mg LD/75 mg/day MD. In a pooled analysis
      evaluating CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A5, CYP2D6, ABCB1, and P2RY12
      polymorphisms (N = 396 healthy subjects), only CYP2C19 had a significant impact
      on antiplatelet response. In healthy CYP2C19 PMs, a clopidogrel regimen of 600-mg
      LD/150 mg/day MD largely overcomes diminished clopi-H4 exposure and antiplatelet
      response, as assessed by MPA levels.

PMID- 21716275
TI  - Pharmacology of synergism among immunosuppressive drugs for transplantation.

PMID- 21716276
TI  - Immunobiology of transplantation: impact on targets for large and small
      molecules.
AB  - Organ transplantation is the preferred method of treatment for many forms of end
      stage organ failure. However, immunosuppressive drugs that are used to avoid
      rejection can result in numerous undesirable effects (infection, malignancy,
      hypertension, diabetes, and accelerated arteriosclerosis). Moreover, they are not
      effective at preventing chronic rejection resulting in late graft loss. This
      review summarizes the fundamental concepts underlying the rejection of solid
      organ allografts with the aim of highlighting potential new targets for
      therapeutics. Future improvement will depend on new therapeutic moieties,
      including biologics, to target various pathways of both the innate and adaptive
      arms of immunity. Results from some of the most recent clinical trials in
      transplantation and emerging new therapies are also discussed.

PMID- 21716277
TI  - Pharmacokinetics and unexpected safety issues of LBM415, a novel oral peptide
      deformylase inhibitor.
AB  - Peptide deformylase (PDF) inhibitors represent a potential new class of
      antibiotics targeting a large number of bacterial species. We studied the
      pharmacokinetics and safety of LBM415, a novel PDF inhibitor, administered as a
      single oral dose at 100-3,000 mg in the fasted state and at 1,000 mg in the fed
      state in healthy volunteers. LBM415 was then administered at dosages ranging from
      100 mg q.d. to 1,000 mg t.i.d. for 11 days. Dose-proportional pharmacokinetics
      was observed, with a peak plasma concentration (C(max)) of 17.85 +/- 5.96 ug/ml
      at 1,000 mg b.i.d. (the projected therapeutic dose) and an area under the
      concentration-time curve (AUC)(0-24h) of 36.83 +/- 10.36 ug/ml.h. The half-life,
      as determined after a 1,000-mg single dose, was 2.18 +/- 0.61 h. The compound was
      well tolerated at low doses, but at the highest dose, 1,000 mg t.i.d., reversible
      cyanosis and low oxygen saturation, attributable to methemoglobinemia, were
      detected on day 11. Oxygen saturation was as low as 88% in one subject on day 11.

PMID- 21716278
TI  - Biomarkers of over-immunosuppression.

PMID- 21716279
TI  - PSICQUIC and PSISCORE: accessing and scoring molecular interactions.

PMID- 21716280
TI  - Coding your way out of a problem.

PMID- 21716281
TI  - Generating high-quality protein binders: a large screening effort pays off.

PMID- 21716282
TI  - Spectral archives: a vision for future proteomics data repositories.

PMID- 21716283
TI  - Fluorogenic pyrosequencing in microreactors.

PMID- 21716285
TI  - Thermal spin current from a ferromagnet to silicon by Seebeck spin tunnelling.
AB  - Heat generation by electric current, which is ubiquitous in electronic devices
      and circuits, raises energy consumption and will become increasingly problematic
      in future generations of high-density electronics. The control and re-use of heat
      are therefore important topics for existing and emerging technologies, including
      spintronics. Recently it was reported that heat flow within a ferromagnet can
      produce a flow of spin angular momentum-a spin current-and an associated voltage.
      This spin Seebeck effect has been observed in metallic, insulating and
      semiconductor ferromagnets with temperature gradients across them. Here we
      describe and report the demonstration of Seebeck spin tunnelling-a distinctly
      different thermal spin flow, of purely interfacial nature-generated in a tunnel
      contact between electrodes of different temperatures when at least one of the
      electrodes is a ferromagnet. The Seebeck spin current is governed by the energy
      derivative of the tunnel spin polarization. By exploiting this in ferromagnet
      oxide-silicon tunnel junctions, we observe thermal transfer of spins from the
      ferromagnet to the silicon without a net tunnel charge current. The induced spin
      accumulation scales linearly with heating power and changes sign when the
      temperature differential is reversed. This thermal spin current can be used by
      itself, or in combination with electrical spin injection, to increase device
      efficiency. The results highlight the engineering of heat transport in spintronic
      devices and facilitate the functional use of heat.

PMID- 21716286
TI  - Crystal structure of a copper-transporting PIB-type ATPase.
AB  - Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type
      ATPases of the class IB (PIB) are essential in these processes, actively
      extruding heavy metals from the cytoplasm of cells. Here we present the structure
      of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, in a copper-free
      form, as determined by X-ray crystallography at 3.2 A resolution. The structure
      indicates a three-stage copper transport pathway involving several conserved
      residues. A PIB-specific transmembrane helix kinks at a double-glycine motif
      displaying an amphipathic helix that lines a putative copper entry point at the
      intracellular interface. Comparisons to Ca(2+)-ATPase suggest an ATPase-coupled
      copper release mechanism from the binding sites in the membrane via an
      extracellular exit site. The structure also provides a framework to analyse
      missense mutations in the human ATP7A and ATP7B proteins associated with Menkes'
      and Wilson's diseases.

PMID- 21716289
TI  - A role for glia in the progression of Rett's syndrome.
AB  - Rett's syndrome (RTT) is an X-chromosome-linked autism spectrum disorder caused
      by loss of function of the transcription factor methyl-CpG-binding protein 2
      (MeCP2). Although MeCP2 is expressed in most tissues, loss of MeCP2 expression
      results primarily in neurological symptoms. Earlier studies suggested the idea
      that RTT is due exclusively to loss of MeCP2 function in neurons. Although
      defective neurons clearly underlie the aberrant behaviours, we and others showed
      recently that the loss of MECP2 from glia negatively influences neurons in a non
      cell-autonomous fashion. Here we show that in globally MeCP2-deficient mice, re
      expression of Mecp2 preferentially in astrocytes significantly improved
      locomotion and anxiety levels, restored respiratory abnormalities to a normal
      pattern, and greatly prolonged lifespan compared to globally null mice.
      Furthermore, restoration of MeCP2 in the mutant astrocytes exerted a non-cell
      autonomous positive effect on mutant neurons in vivo, restoring normal dendritic
      morphology and increasing levels of the excitatory glutamate transporter VGLUT1.
      Our study shows that glia, like neurons, are integral components of the
      neuropathology of RTT, and supports the targeting of glia as a strategy for
      improving the associated symptoms.

PMID- 21716290
TI  - Excitatory transmission from the amygdala to nucleus accumbens facilitates reward
      seeking.
AB  - The basolateral amygdala (BLA) has a crucial role in emotional learning
      irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is
      thought to modulate cue-triggered motivated behaviours, but our understanding of
      the interaction between these two brain regions has been limited by the inability
      to manipulate neural-circuit elements of this pathway selectively during
      behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation
      or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with
      intracranial pharmacology and ex vivo electrophysiology. Here we show that
      optical stimulation of the pathway from the BLA to the NAc in mice reinforces
      behavioural responding to earn additional optical stimulation of these synaptic
      inputs. Optical stimulation of these glutamatergic fibres required intra-NAc
      dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief
      optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of
      sucrose, demonstrating an important role of this specific pathway in controlling
      naturally occurring reward-related behaviour. Moreover, although optical
      stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc
      also elicited reliable excitatory synaptic responses, optical self-stimulation
      behaviour was not observed by activation of this pathway. These data indicate
      that whereas the BLA is important for processing both positive and negative
      affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with
      dopamine signalling in the NAc, promotes motivated behavioural responding. Thus,
      optogenetic manipulation of anatomically distinct synaptic inputs to the NAc
      reveals functionally distinct properties of these inputs in controlling reward
      seeking behaviours.

PMID- 21716291
TI  - Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined
      factors.
AB  - The location and timing of cellular differentiation must be stringently
      controlled for proper organ formation. Normally, hepatocytes differentiate from
      hepatic progenitor cells to form the liver during development. However, previous
      studies have shown that the hepatic program can also be activated in non-hepatic
      lineage cells after exposure to particular stimuli or fusion with hepatocytes.
      These unexpected findings suggest that factors critical to hepatocyte
      differentiation exist and become activated to induce hepatocyte-specific
      properties in different cell types. Here, by screening the effects of twelve
      candidate factors, we identify three specific combinations of two transcription
      factors, comprising Hnf4alpha plus Foxa1, Foxa2 or Foxa3, that can convert mouse
      embryonic and adult fibroblasts into cells that closely resemble hepatocytes in
      vitro. The induced hepatocyte-like (iHep) cells have multiple hepatocyte-specific
      features and reconstitute damaged hepatic tissues after transplantation. The
      generation of iHep cells may provide insights into the molecular nature of
      hepatocyte differentiation and potential therapies for liver diseases.

PMID- 21716292
TI  - Enhancement of autophagy is a potential modality for tumors refractory to
      radiotherapy.
AB  - Radiotherapy is a well-established treatment for cancer. However, the existence
      of radioresistant cells is one of the major obstacles in radiotherapy. In order
      to understand the mechanism of cellular radioresistance and develop more
      effective radiotherapy, we have established clinically relevant radioresistant
      (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray
      (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic
      cells in parental cells, which was exiguous in CRR cells, suggesting that
      autophagic cell death is involved in cellular radiosensitivity. An autophagy
      inducer, rapamycin sensitized CRR cells to the level of parental cells and
      suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced
      radioresistance of parental cells. Furthermore, inhibition of autophagy by
      knockdown of Beclin-1 made parental cells radioresistant to acute radiation.
      These suggest that the suppression of autophagic cell death but not apoptosis is
      mainly involved in cellular radioresistance. Therefore, the enhancement of
      autophagy may have a considerable impact on the treatment of radioresistant
      tumor.

PMID- 21716293
TI  - Diverse system stresses: common mechanisms of chromosome fragmentation.
AB  - Chromosome fragmentation (C-Frag) is a newly identified MCD (mitotic cell death),
      distinct from apoptosis and MC (mitotic catastrophe). As different molecular
      mechanisms can induce C-Frag, we hypothesize that the general mechanism of its
      induction is a system response to cellular stress. A clear link between C-Frag
      and diverse system stresses generated from an array of molecular mechanisms is
      shown. Centrosome amplification, which is also linked to diverse mechanisms of
      stress, is shown to occur in association with C-Frag. This led to a new model
      showing that diverse stresses induce common, MCD. Specifically, different
      cellular stresses target the integral chromosomal machinery, leading to system
      instability and triggering of MCD by C-Frag. This model of stress-induced cell
      death is also applicable to other types of cell death. The current study solves
      the previously confusing relationship between the diverse molecular mechanisms of
      chromosome pulverization, suggesting that incomplete C-Frag could serve as the
      initial event responsible for forms of genome chaos including chromothripsis. In
      addition, multiple cell death types are shown to coexist with C-Frag and it is
      more dominant than apoptosis at lower drug concentrations. Together, this study
      suggests that cell death is a diverse group of highly heterogeneous events that
      are linked to stress-induced system instability and evolutionary potential.

PMID- 21716294
TI  - Improved accuracy for the detection of sleep apnea-related surges in blood
      pressure.

PMID- 21716295
TI  - Negative feedforward control of body fluid homeostasis by hepatorenal reflex.
AB  - The liver, well known for its role in metabolism, clearance and storage can also
      be regarded as a sensory organ. The liver is an ideal place to monitor the
      quality and quantity of absorbed substances, because portal blood delivers
      substances absorbed from the intestine to the liver and these substances
      circulate in the hepatic vasculature before substances enter the systemic
      circulation. Sodium (Na(+))-sensitive mechanism exists in the liver; it is
      stimulated by the increase in Na(+) concentration in the portal vein, and then
      hepatorenal reflex is triggered. Renal sympathetic nerve activity is reflexively
      decreased and urinary Na(+) excretion is increased. This Na(+)-sensitive
      hepatorenal reflex has a significant role in post-prandial natriuresis. However,
      the long-term role of this reflex in Na(+) homeostasis may be less important,
      probably because of the desensitization of Na(+)-sensitive mechanisms. Na(+)-K(+)
      2Cl(-) cotransporter (NKCC1) is involved in the hepatoportal Na(+)-sensitive
      mechanism, and NKCC1 expression is reduced if the hepatoportal region is exposed
      to high Na(+) concentrations for a long time. This situation occurs when animals
      intake a high-sodium chloride diet for a long time. Liver cirrhosis also impairs
      the Na(+)-sensitive hepatorenal reflex. Hepatoportal baroreceptor-induced renal
      sympathetic excitation and the impaired Na(+)-sensitive hepatorenal reflex may
      partially explain the Na(+) retention in liver cirrhosis.

PMID- 21716296
TI  - Relationship between ED and depression among middle-aged and elderly men in
      Korea: Hallym aging study.
AB  - The aim of this study was to investigate the relationship between ED and
      depression. The survey was conducted among persons enrolled in panel study about
      Quality of Life of Korean Elderly Project at the Institute for Aging studies.
      Subjects were 203 men aged 45-74 years (mean age 65.5 years). ED was assessed by
      International Index of Erectile Function 5 (IIEF-5) score (Korean version), and
      depression was assessed by the Geriatric Depression Scale (GDS, Korean version).
      The baseline questionnaires included demographic and health history information.
      The age-adjusted prevalence of current depression by GDS (>=18), of ED by IIEF-5
      score (<18), and of concomitant ED and depression were 12.2%, 28.2% and 11.0%,
      respectively. GDS increased according to severity of ED, adjusted for age,
      marital status, education, smoking, alcohol, hypertension, regular exercise,
      total cholesterol level, fasting blood sugar, body mass index (P<0.001, by
      analysis of covariance). ED was strongly associated with depression symptoms
      after controlling for potential confounding factors using logistic regression.
      Compared with GDS <8, odds ratios and 95% confidence intervals for 12-17 GDS and
      18 or more GDS were 3.38 (1.30-8.77) and 6.56 (2.18-19.81), respectively. ED is
      significantly associated with highly depressive symptoms, regardless of age,
      health habit or concomitant comorbidity. Our results demonstrate that
      multidisciplinary approaches are important for the successful treatment of ED.

PMID- 21716297
TI  - The effect of simvastatin in penile erection: a randomized, double-blind, placebo
      controlled clinical trial (Simvastatin treatment for erectile dysfunction-STED
      TRIAL).
AB  - The aim of the study is to evaluate the effect of simvastatin in erectile
      dysfunction (ED) secondary to endothelial dysfunction. This study is a double
      blind, randomized, placebo-controlled, clinical trial in patients with ED and
      endothelial dysfunction. Patients were randomized to receive 20 mg simvastatin (n
      = 21) or placebo (n = 20) daily for 6 months and subsequently 10 mg of vardenafil
      on demand for 4 weeks. Serum cholesterol, hormone profile, ultrasensitive C
      reactive protein, the International Index of Erectile Dysfunction (IIEF) and the
      ED Index of Treatment Satisfaction were evaluated. There was a significant
      reduction in serum cholesterol in the treatment group. The hormonal profile
      remained unaltered. There was no difference in the IIEF between the groups at
      follow-up, although, at the beginning, 26% of the patients of both groups
      presented with mild ED and 74% with moderate-to-severe ED; at the end of the 7th
      month, all patients from the simvastatin group progressed to mild ED, compared
      with only 83% in the placebo group. There was no statistically significant
      difference in penile erection after intake of simvastatin or placebo. This study
      does not support the use of simvastatin as erectogenic medication. Further
      studies are necessary to verify if simvastatin has any beneficial effect on ED.

PMID- 21716298
TI  - Gene-eluting stents: non-viral, liposome-based gene delivery of eNOS to the blood
      vessel wall in vivo results in enhanced endothelialization but does not reduce
      restenosis in a hypercholesterolemic model.
AB  - Although successful, drug-eluting stents require significant periods of dual anti
      platelet therapy with a persistent risk of late stent thrombosis due to
      inhibition of re-endothelialization. Endothelial regeneration is desirable to
      protect against in-stent thrombosis. Gene-eluting stents may be an alternative
      allowing inhibition of neointima and regenerating endothelium. We have shown that
      adenoviral endothelial nitric oxide synthase (eNOS) delivery can result in
      significantly decreased neointimal formation and enhanced re-endothelialization.
      Here, we examined non-viral reporter and therapeutic gene delivery from a stent.
      We coated lipoplexes directly onto the surface of stents. These lipostents were
      then deployed in the injured external iliac artery of either normal or
      hypercholesterolemic New Zealand White rabbits and recovered after 28 days.
      Lipoplexes composed of lipofectin and a reporter lacZ gene or therapeutic eNOS
      gene were used. We demonstrated efficient gene delivery at 28 days post
      deployment in the media (21.3+/-7.5%) and neointima (26.8+/-11.2%). Liposomal
      delivery resulted in expression in macrophages between the stent struts. This
      resulted in improved re-endothelialization as detected by two independent
      measures compared with vector and stent controls (P<0.05 for both). However, in
      contrast to viral delivery of eNOS, liposomal eNOS does not reduce restenosis
      rates. The differing cell populations targeted by lipoplexes compared with
      adenoviral vectors may explain their ability to enhance re-endothelialization
      without affecting restenosis. Liposome-mediated gene delivery can result in
      prolonged and localized transgene expression in the blood vessel wall in vivo.
      Furthermore, lipoeNOS delivery to the blood vessel wall results in accelerated re
      endothelialization; however, it does not reduce neointimal formation.

PMID- 21716299
TI  - Successful attenuation of humoral immunity to viral capsid and transgenic protein
      following AAV-mediated gene transfer with a non-depleting CD4 antibody and
      cyclosporine.
AB  - The ability of transient immunosuppression with a combination of a non-depleting
      anti-CD4 (NDCD4) antibody and cyclosporine (CyA) to abrogate immune reactivity to
      both adeno-associated viral vector (AAV) and its transgene product was evaluated.
      This combination of immunosuppressants resulted in a 20-fold reduction in the
      resulting anti-AAV8 antibody titres, to levels in naive mice, following
      intravenous administration of 2 * 10(12) AAV8 vector particles per kg to
      immunocompetent mice. This allowed efficient transduction upon secondary
      challenge with vector pseudotyped with the same capsid. Persistent tolerance did
      not result, however, as an anti-AAV8 antibody response was elicited upon
      rechallenge with AAV8 without immunosuppression. The route of vector
      administration, vector dose, AAV serotype or the concomitant administration of
      adenoviral vector appeared to have little impact on the ability of the NDCD4
      antibody and CyA combination to moderate the primary humoral response to AAV
      capsid proteins. The combination of NDCD4 and CyA also abrogated the humoral
      response to the transgene product, that otherwise invariably would occur,
      following intramuscular injection of AAV5, leading to stable transgene
      expression. These observations could significantly improve the prospects of using
      rAAV vectors for chronic disorders by allowing for repeated vector administration
      and avoiding the development of antibodies to the transgene product.

PMID- 21716300
TI  - Encapsulated engineered myoblasts can cure Hurler syndrome: preclinical
      experiments in the mouse model.
AB  - Mucopolysaccharidosis type I (MPSI) is an autosomic recessive, lysosomal storage
      disorder due to the deficit of the enzyme alpha-L-iduronidase (IDUA). The disease
      accounts for a general impairment of tissue and organ functions, mainly including
      heart disease, corneal clouding, organomegaly, skeletal malformations and joint
      stiffness. Neurological deterioration affects the severe forms. Both haemopoietic
      stem cell transplantation and enzyme replacement therapy can be applied to the
      treatment of the disorder; however, they both present several limitations. Thus,
      the search for alternative strategies to complement the present procedures is
      highly desirable. A murine myoblast cell line engineered to overexpress IDUA was
      generated and enclosed in alginate microcapsules, which were intra-peritoneally
      implanted in the MPSI mouse model. Plasma and tissue enzyme activity induced by
      the treatment and urinary and tissue glycosaminoglycan content were monitored in
      the animals, progressively sacrificed up to 4 months after implantation.
      Significant induction of enzyme activity and reduction of glycosaminoglycan
      accumulation were detected in the implanted animals, complete normalization of
      deposits was achieved in two animals. Intra-peritoneal implantation of alginate
      microcapsule confirms to be a valid approach as an endogenous enzyme replacement
      procedure.

PMID- 21716301
TI  - Muscle gene electrotransfer is increased by the antioxidant tempol in mice.
AB  - Electropermeabilization (EP) is an effective method of gene transfer into
      different tissues. During EP, reactive oxygen species (ROS) are formed, which
      could affect transfection efficiency. The role of generated ROS and the role of
      antioxidants in electrotransfer in myoblasts in vitro and in Musculus tibialis
      cranialis in mice were, therefore, investigated. We demonstrate in the study that
      during EP of C2C12 myoblasts, ROS are generated on the surface of the cells,
      which do not induce long-term genomic DNA damage. Plasmid DNA for transfection
      (pEGFP-N1), which is present outside the cells during EP, neutralizes the
      generated ROS. The ROS generation is proportional to the amplitude of the
      electric pulses and can be scavenged by antioxidants, such as vitamin C or
      tempol. When antioxidants were used during gene electrotransfer, the transfection
      efficiency of C2C12 myoblasts was statistically significantly increased 1.6-fold
      with tempol. Also in vivo, the transfection efficiency of M. tibialis cranialis
      in mice was statistically significantly increased 1.4-fold by tempol. The study
      indicates that ROS are generated on cells during EP and can be scavenged by
      antioxidants. Specifically, tempol can be used to improve gene electrotransfer
      into the muscle and possibly also to other tissues.

PMID- 21716302
TI  - Transcription factor plasmid binding modulates microtubule interactions and
      intracellular trafficking during gene transfer.
AB  - For non-viral gene delivery to be successful, plasmids must move through the
      cytoplasm to the nucleus in order to be transcribed. While the cytoskeletal
      meshwork acts as a barrier to plasmid DNA movement in the cytoplasm, the
      microtubule network is required for directed plasmid trafficking to the nucleus.
      We have shown previously that plasmid-microtubule interactions require
      cytoplasmic adapter proteins such as molecular motors, transcription factors
      (TFs) and importins. However, not all plasmid sequences support these
      interactions to allow movement to the nucleus. We now demonstrate that
      microtubule-DNA interactions can show sequence specificity with promoters
      containing binding sites for cyclic AMP response-element binding protein (CREB),
      including the cytomegalovirus immediate early promoter (CMV(iep)). Plasmids
      containing CREB-binding sites showed stringent interactions in an in vitro
      microtubule-binding assay. Using microinjection and real-time particle tracking,
      we show that the inclusion of TF binding sites within plasmids permits
      cytoplasmic trafficking of plasmids during gene transfer. We found that CREB
      binding sites are bound by CREB in the cytoplasm during transfection, and allow
      for enhanced rates of movement and subsequent nuclear accumulation. Moreover,
      small interfering RNA knockdown of CREB prevented this enhanced trafficking.
      Therefore, TF binding sites within plasmids are necessary for interactions with
      microtubules and enhance movement to the nucleus.

PMID- 21716303
TI  - Long-term safety of intramuscular gene transfer of non-viral FGF1 for peripheral
      artery disease.
AB  - Peripheral artery disease is a progressive disease. Primary ischemic leg symptoms
      are muscle fatigue, discomfort or pain during ambulation, known as intermittent
      claudication. The most severe manifestation of peripheral artery disease is
      critical limb ischemia (CLI). The long-term safety of gene therapy in peripheral
      artery disease remains unclear. This four center peripheral artery disease
      registry was designed to evaluate the long-term safety of the intramuscular non
      viral fibroblast growth factor-1 (NV1FGF), a plasmid-based angiogenic gene for
      local expression of fibroblast growth factor-1 versus placebo in patients with
      peripheral artery disease who had been included in five different phase I and II
      trials. Here we report a 3-year follow-up in patients suffering from CLI or
      intermittent claudication. There were 93 evaluable patients, 72 of them in
      Fontaine stage IV (47 NV1FGF versus 25 placebo) and 21 patients in Fontaine stage
      IIb peripheral artery disease (15 NV1FGF versus 6 placebo). Safety parameters
      included rates of non-fatal myocardial infarction (MI), stroke, death, cancer,
      retinopathy and renal dysfunction. At 3 years, in 93 patients included this
      registry, there was no increase in retinopathy or renal dysfunction associated
      with delivery of this angiogenic factor. There was also no difference in the
      number of strokes, MI or deaths, respectively, for NV1FGF versus placebo. In the
      CLI group, new cancer occurred in two patients in the NV1FGF group. Conclusions
      that can be drawn from this relatively small patient group are limited because of
      the number of patients followed and can only be restricted to safety. Yet, data
      presented may be valuable concerning rates in cancer, retinopathy, MI or strokes
      following angiogenesis gene therapy in the absence of any long-term data in
      angiogenesis gene therapy. It may take several years until data from larger
      patient populations will become available.

PMID- 21716304
TI  - De novo metagenomic assembly reveals abundant novel major lineage of Archaea in
      hypersaline microbial communities.
AB  - This study describes reconstruction of two highly unusual archaeal genomes by de
      novo metagenomic assembly of multiple, deeply sequenced libraries from surface
      waters of Lake Tyrrell (LT), a hypersaline lake in NW Victoria, Australia.
      Lineage-specific probes were designed using the assembled genomes to visualize
      these novel archaea, which were highly abundant in the 0.1-0.8 MUm size fraction
      of lake water samples. Gene content and inferred metabolic capabilities were
      highly dissimilar to all previously identified hypersaline microbial species.
      Distinctive characteristics included unique amino acid composition, absence of
      Gvp gas vesicle proteins, atypical archaeal metabolic pathways and unusually
      small cell size (approximately 0.6 MUm diameter). Multi-locus phylogenetic
      analyses demonstrated that these organisms belong to a new major euryarchaeal
      lineage, distantly related to halophilic archaea of class Halobacteria.
      Consistent with these findings, we propose creation of a new archaeal class,
      provisionally named 'Nanohaloarchaea'. In addition to their high abundance in LT
      surface waters, we report the prevalence of Nanohaloarchaea in other hypersaline
      environments worldwide. The simultaneous discovery and genome sequencing of a
      novel yet ubiquitous lineage of uncultivated microorganisms demonstrates that
      even historically well-characterized environments can reveal unexpected diversity
      when analyzed by metagenomics, and advances our understanding of the ecology of
      hypersaline environments and the evolutionary history of the archaea.

PMID- 21716305
TI  - Community genomic analysis of an extremely acidophilic sulfur-oxidizing biofilm.
AB  - Highly acidic (pH 0-1) biofilms, known as 'snottites', form on the walls and
      ceilings of hydrogen sulfide-rich caves. We investigated the population
      structure, physiology and biogeochemistry of these biofilms using metagenomics,
      rRNA methods and lipid geochemistry. Snottites from the Frasassi cave system
      (Italy) are dominated (>70% of cells) by Acidithiobacillus thiooxidans, with
      smaller populations including an archaeon in the uncultivated 'G-plasma' clade of
      Thermoplasmatales (>15%) and a bacterium in the Acidimicrobiaceae family (>5%).
      Based on metagenomic evidence, the Acidithiobacillus population is autotrophic
      (ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), carboxysomes) and
      oxidizes sulfur by the sulfide-quinone reductase and sox pathways. No reads
      matching nitrogen fixation genes were detected in the metagenome, whereas
      multiple matches to nitrogen assimilation functions are present, consistent with
      geochemical evidence, that fixed nitrogen is available in the snottite
      environment to support autotrophic growth. Evidence for adaptations to extreme
      acidity include Acidithiobacillus sequences for cation transporters and hopanoid
      synthesis, and direct measurements of hopanoid membrane lipids. Based on combined
      metagenomic, molecular and geochemical evidence, we suggest that
      Acidithiobacillus is the snottite architect and main primary producer, and that
      snottite morphology and distributions in the cave environment are directly
      related to the supply of C, N and energy substrates from the cave atmosphere.

PMID- 21716306
TI  - High-throughput single-cell sequencing identifies photoheterotrophs and
      chemoautotrophs in freshwater bacterioplankton.
AB  - Recent discoveries suggest that photoheterotrophs (rhodopsin-containing bacteria
      (RBs) and aerobic anoxygenic phototrophs (AAPs)) and chemoautotrophs may be
      significant for marine and freshwater ecosystem productivity. However, their
      abundance and taxonomic identities remain largely unknown. We used a combination
      of single-cell and metagenomic DNA sequencing to study the predominant
      photoheterotrophs and chemoautotrophs inhabiting the euphotic zone of temperate,
      physicochemically diverse freshwater lakes. Multi-locus sequencing of 712 single
      amplified genomes, generated by fluorescence-activated cell sorting and whole
      genome multiple displacement amplification, showed that most of the cosmopolitan
      freshwater clusters contain photoheterotrophs. These comprised at least 10-23% of
      bacterioplankton, and RBs were the dominant fraction. Our data demonstrate that
      Actinobacteria, including clusters acI, Luna and acSTL, are the predominant
      freshwater RBs. We significantly broaden the known taxonomic range of freshwater
      RBs, to include Alpha-, Beta-, Gamma- and Deltaproteobacteria, Verrucomicrobia
      and Sphingobacteria. By sequencing single cells, we found evidence for inter
      phyla horizontal gene transfer and recombination of rhodopsin genes and
      identified specific taxonomic groups involved in these evolutionary processes.
      Our data suggest that members of the ubiquitous betaproteobacteria
      Polynucleobacter spp. are the dominant AAPs in temperate freshwater lakes.
      Furthermore, the RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) gene
      was found in several single cells of Betaproteobacteria, Bacteroidetes and
      Gammaproteobacteria, suggesting that chemoautotrophs may be more prevalent among
      aerobic bacterioplankton than previously thought. This study demonstrates the
      power of single-cell DNA sequencing addressing previously unresolved questions
      about the metabolic potential and evolutionary histories of uncultured
      microorganisms, which dominate most natural environments.

PMID- 21716307
TI  - Microbial community structure of Arctic multiyear sea ice and surface seawater by
      454 sequencing of the 16S RNA gene.
AB  - Dramatic decreases in the extent of Arctic multiyear ice (MYI) suggest this
      environment may disappear as early as 2100, replaced by ecologically different
      first-year ice. To better understand the implications of this loss on microbial
      biodiversity, we undertook a detailed census of the microbial community in MYI at
      two sites near the geographic North Pole using parallel tag sequencing of the 16S
      rRNA gene. Although the composition of the MYI microbial community has been
      characterized by previous studies, microbial community structure has not been.
      Although richness was lower in MYI than in underlying surface water, we found
      diversity to be comparable using the Simpson and Shannon's indices (for Simpson
      t=0.65, P=0.56; for Shannon t=0.25, P=0.84 for a Student's t-test of mean
      values). Cyanobacteria, comprising 6.8% of reads obtained from MYI, were observed
      for the first time in Arctic sea ice. In addition, several low-abundance clades
      not previously reported in sea ice were present, including the phylum TM7 and the
      classes Spartobacteria and Opitutae. Members of Coraliomargarita, a recently
      described genus of the class Opitutae, were present in sufficient numbers to
      suggest niche occupation within MYI.

PMID- 21716308
TI  - The oral metagenome in health and disease.
AB  - The oral cavity of humans is inhabited by hundreds of bacterial species and some
      of them have a key role in the development of oral diseases, mainly dental caries
      and periodontitis. We describe for the first time the metagenome of the human
      oral cavity under health and diseased conditions, with a focus on supragingival
      dental plaque and cavities. Direct pyrosequencing of eight samples with different
      oral-health status produced 1 Gbp of sequence without the biases imposed by PCR
      or cloning. These data show that cavities are not dominated by Streptococcus
      mutans (the species originally identified as the ethiological agent of dental
      caries) but are in fact a complex community formed by tens of bacterial species,
      in agreement with the view that caries is a polymicrobial disease. The analysis
      of the reads indicated that the oral cavity is functionally a different
      environment from the gut, with many functional categories enriched in one of the
      two environments and depleted in the other. Individuals who had never suffered
      from dental caries showed an over-representation of several functional
      categories, like genes for antimicrobial peptides and quorum sensing. In
      addition, they did not have mutans streptococci but displayed high recruitment of
      other species. Several isolates belonging to these dominant bacteria in healthy
      individuals were cultured and shown to inhibit the growth of cariogenic bacteria,
      suggesting the use of these commensal bacterial strains as probiotics to promote
      oral health and prevent dental caries.

PMID- 21716309
TI  - Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses
      of cystic fibrosis children have implications for chronic lung infection.
AB  - The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the
      airways of patients suffering from cystic fibrosis (CF). Depending on early
      treatment regimens, the colonization will, with high probability, develop into
      chronic infections sooner or later, and it is important to establish under which
      conditions the switch to chronic infection takes place. In association with a
      recently established sinus surgery treatment program for CF patients at the
      Copenhagen CF Center, colonization of the paranasal sinuses with P. aeruginosa
      has been investigated, paralleled by sampling of sputum from the same patients.
      On the basis of genotyping and phenotypic characterization including
      transcription profiling, the diversity of the P. aeruginosa populations in the
      sinuses and the lower airways was investigated and compared. The observations
      made from several children show that the paranasal sinuses constitute an
      important niche for the colonizing bacteria in many patients. The paranasal
      sinuses often harbor distinct bacterial subpopulations, and in the early
      colonization phases there seems to be a migration from the sinuses to the lower
      airways, suggesting that independent adaptation and evolution take place in the
      sinuses. Importantly, before the onset of chronic lung infection, lineages with
      mutations conferring a large fitness benefit in CF airways such as mucA and lasR
      as well as small colony variants and antibiotic-resistant clones are part of the
      sinus populations. Thus, the paranasal sinuses potentially constitute a protected
      niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs
      and pave the way for subsequent chronic lung infections.

PMID- 21716310
TI  - Metatranscriptomic analysis of autonomously collected and preserved marine
      bacterioplankton.
AB  - Planktonic microbial activity and community structure is dynamic, and can change
      dramatically on time scales of hours to days. Yet for logistical reasons, this
      temporal scale is typically under-sampled in the marine environment. In order to
      facilitate higher-resolution, long-term observation of microbial diversity and
      activity, we developed a protocol for automated collection and fixation of marine
      microbes using the Environmental Sample Processor (ESP) platform. The protocol
      applies a preservative (RNALater) to cells collected on filters, for long-term
      storage and preservation of total cellular RNA. Microbial samples preserved using
      this protocol yielded high-quality RNA after 30 days of storage at room
      temperature, or onboard the ESP at in situ temperatures. Pyrosequencing of
      complementary DNA libraries generated from ESP-collected and preserved samples
      yielded transcript abundance profiles nearly indistinguishable from those derived
      from conventionally treated replicate samples. To demonstrate the utility of the
      method, we used a moored ESP to remotely and autonomously collect Monterey Bay
      seawater for metatranscriptomic analysis. Community RNA was extracted and
      pyrosequenced from samples collected at four time points over the course of a
      single day. In all four samples, the oxygenic photoautotrophs were predominantly
      eukaryotic, while the bacterial community was dominated by Polaribacter-like
      Flavobacteria and a Rhodobacterales bacterium sharing high similarity with
      Rhodobacterales sp. HTCC2255. However, each time point was associated with
      distinct species abundance and gene transcript profiles. These laboratory and
      field tests confirmed that autonomous collection and preservation is a feasible
      and useful approach for characterizing the expressed genes and environmental
      responses of marine microbial communities.

PMID- 21716311
TI  - Impact of training sets on classification of high-throughput bacterial 16s rRNA
      gene surveys.
AB  - Taxonomic classification of the thousands-millions of 16S rRNA gene sequences
      generated in microbiome studies is often achieved using a naive Bayesian
      classifier (for example, the Ribosomal Database Project II (RDP) classifier), due
      to favorable trade-offs among automation, speed and accuracy. The resulting
      classification depends on the reference sequences and taxonomic hierarchy used to
      train the model; although the influence of primer sets and classification
      algorithms have been explored in detail, the influence of training set has not
      been characterized. We compared classification results obtained using three
      different publicly available databases as training sets, applied to five
      different bacterial 16S rRNA gene pyrosequencing data sets generated (from human
      body, mouse gut, python gut, soil and anaerobic digester samples). We observed
      numerous advantages to using the largest, most diverse training set available,
      that we constructed from the Greengenes (GG) bacterial/archaeal 16S rRNA gene
      sequence database and the latest GG taxonomy. Phylogenetic clusters of previously
      unclassified experimental sequences were identified with notable improvements
      (for example, 50% reduction in reads unclassified at the phylum level in mouse
      gut, soil and anaerobic digester samples), especially for phylotypes belonging to
      specific phyla (Tenericutes, Chloroflexi, Synergistetes and Candidate phyla TM6,
      TM7). Trimming the reference sequences to the primer region resulted in
      systematic improvements in classification depth, and greatest gains at higher
      confidence thresholds. Phylotypes unclassified at the genus level represented a
      greater proportion of the total community variation than classified operational
      taxonomic units in mouse gut and anaerobic digester samples, underscoring the
      need for greater diversity in existing reference databases.

PMID- 21716312
TI  - Saliva microbiomes distinguish caries-active from healthy human populations.
AB  - The etiology of dental caries remains elusive because of our limited
      understanding of the complex oral microbiomes. The current methodologies have
      been limited by insufficient depth and breadth of microbial sampling, paucity of
      data for diseased hosts particularly at the population level, inconsistency of
      sampled sites and the inability to distinguish the underlying microbial factors.
      By cross-validating 16S rRNA gene amplicon-based and whole-genome-based deep
      sequencing technologies, we report the most in-depth, comprehensive and
      collaborated view to date of the adult saliva microbiomes in pilot populations of
      19 caries-active and 26 healthy human hosts. We found that: first, saliva
      microbiomes in human population were featured by a vast phylogenetic diversity
      yet a minimal organismal core; second, caries microbiomes were significantly more
      variable in community structure whereas the healthy ones were relatively
      conserved; third, abundance changes of certain taxa such as overabundance of
      Prevotella Genus distinguished caries microbiota from healthy ones, and
      furthermore, caries-active and normal individuals carried different arrays of
      Prevotella species; and finally, no 'caries-specific' operational taxonomic units
      (OTUs) were detected, yet 147 OTUs were 'caries associated', that is,
      differentially distributed yet present in both healthy and caries-active
      populations. These findings underscored the necessity of species- and strain
      level resolution for caries prognosis, and were consistent with the ecological
      hypothesis where the shifts in community structure, instead of the presence or
      absence of particular groups of microbes, underlie the cariogenesis.

PMID- 21716313
TI  - Association of Toll-like receptor 10 and susceptibility to Crohn's disease
      independent of NOD2.
AB  - Impaired innate inflammatory response has a key role in the Crohn's disease (CD)
      pathogenesis. The aim of this study was to investigate the possible role of the
      TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients
      (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6
      cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA
      quantification were performed using TaqMan assays. Nucleotide-binding
      oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci
      interaction was analyzed by logistic regression and multifactor-dimensionality
      reduction (MDR). Entropy-based analysis was used to interpret combination
      effects. One TLR10 haplotype (TLR10(GGGG)) was found associated with CD
      susceptibility in both cohorts, individuals with two copies had approximately
      twofold more risk of CD susceptibility than individuals having no copies (odds
      ratio=1.89, P-value=0.0002). No differences in the mRNA levels were observed
      among the genotypes. The strongest model for predicting CD risk according to the
      MDR analysis was a two-locus model including NOD2 mutations and TLR10(GGGG)
      haplotype (P(c)<0.0001). The interaction gain attributed to the combination of
      both genes was negative (IG=-2.36%), indicating redundancy or independent
      effects. Our results support association of the TLR10 gene with CD
      susceptibility. The effect of TLR10 would be independent of NOD2, suggesting
      different signaling pathways for both genes.

PMID- 21716314
TI  - Pathway-based analysis of genetic susceptibility to cervical cancer in situ: HLA
      DPB1 affects risk in Swedish women.
AB  - We have conducted a pathway-based analysis of genome-wide single-nucleotide
      polymorphism (SNP) data in order to identify genetic susceptibility factors for
      cervical cancer in situ. Genotypes derived from Affymetrix 500k or 5.0 arrays for
      1076 cases and 1426 controls were analyzed for association, and pathways with
      enriched signals were identified using the SNP ratio test. The most strongly
      associated KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were Asthma
      (empirical P=0.03), Folate biosynthesis (empirical P=0.04) and Graft-versus-host
      disease (empirical P=0.05). Among the 11 top-ranking pathways were 6 related to
      the immune response with the common denominator being genes in the major
      histocompatibility complex (MHC) region on chromosome 6. Further investigation of
      the MHC revealed a clear effect of HLA-DPB1 polymorphism on disease
      susceptibility. At a functional level, DPB1 alleles associated with risk and
      protection differ in key amino-acid residues affecting peptide-binding motifs in
      the extracellular domains. The results illustrate the value of pathway-based
      analysis to mine genome-wide data, and point to the importance of the MHC region
      and specifically the HLA-DPB1 locus for susceptibility to cervical cancer.

PMID- 21716315
TI  - A cytokine gene screen uncovers SOCS1 as genetic risk factor for multiple
      sclerosis.
AB  - Cytokine and cytokine receptor genes, including IL2RA, IL7R and IL12A, are known
      risk factors for multiple sclerosis (MS). Excitotoxic oligodendroglial death
      mediated by glutamate receptors contributes to demyelinating reactions. In the
      present study, we screened 368 single-nucleotide polymorphisms (SNPs) in 55 genes
      or gene clusters coding for cytokines, cytokine receptors, suppressors of
      cytokine signaling (SOCS), complement factors and glutamate receptors for
      association with MS in a Spanish-Basque resident population. Top-scoring SNPs
      were found within or nearby the genes coding for SOCS-1 (P=0.0005), interleukin
      28 receptor, alpha chain (P=0.0008), oncostatin M receptor (P=0.002) and
      interleukin-22 receptor, alpha 2 (IL22RA2; P=0.003). The SOCS1 rs243324 variant
      was validated as risk factor for MS in a separate cohort of 3919 MS patients and
      4003 controls (combined Cochran-Mantel-Haenszel P=0.00006; odds ratio (OR)=1.13;
      95% confidence interval (CI)=1.07-1.20). In addition, the T allele of rs243324
      was consistently increased in relapsing-remitting/secondary progressive versus
      primary-progressive MS patients, in each of the six data sets used in this study
      (P(CMH)=0.0096; OR=1.24; 95% CI 1.05-1.46). The association with SOCS1 appears
      independent from the chr16MS risk locus CLEC16A.

PMID- 21716316
TI  - CLC and IFNAR1 are differentially expressed and a global immunity score is
      distinct between early- and late-onset colorectal cancer.
AB  - Colorectal cancer (CRC) incidence increases with age, and early onset of the
      disease is an indication of genetic predisposition, estimated to cause up to 30%
      of all cases. To identify genes associated with early-onset CRC, we investigated
      gene expression levels within a series of young patients with CRCs who are not
      known to carry any hereditary syndromes (n=24; mean 43 years at diagnosis), and
      compared this with a series of CRCs from patients diagnosed at an older age
      (n=17; mean 79 years). Two individual genes were found to be differentially
      expressed between the two groups, with statistical significance; CLC was higher
      and IFNAR1 was less expressed in early-onset CRCs. Furthermore, genes located at
      chromosome band 19q13 were found to be enriched significantly among the genes
      with higher expression in the early-onset samples, including CLC. An elevated
      immune content within the early-onset group was observed from the differentially
      expressed genes. By application of outlier statistics, H3F3A was identified as a
      top candidate gene for a subset of the early-onset CRCs. In conclusion, CLC and
      IFNAR1 were identified to be overall differentially expressed between early- and
      late-onset CRC, and are important in the development of early-onset CRC.

PMID- 21716317
TI  - Association of adipokines with blood pressure in rural Chinese adolescents.
AB  - Previous research has demonstrated that adipokines influence blood pressure (BP).
      Limited data exist in healthy adolescents, who are in a critical period for
      preventing the development of high BP. This study investigated the association of
      leptin, adiponectin and the leptin-to-adiponectin ratio (LAR) with BP in rural
      Chinese adolescents. This report included 1245 adolescents (average body mass
      index: 19.3 kg m(-2)) aged 13-21 years from an established twin cohort. We
      examined gender-specific associations between plasma adipokines and BP, with
      adjustment for measures of adiposity and insulin resistance (IR). We estimated
      the genetic contribution to adipokines using the twin design and Cholesky
      decomposition models. There was no correlation between leptin and adiponectin
      levels. Leptin was positively associated with systolic blood pressure (SBP) in
      males and diastolic blood pressure in females, but the association disappeared
      after adjusting for adiposity and IR. LAR was positively associated with SBP
      (beta(s.e.): 1.94(0.45)), P<0.01), adiponectin was negatively associated with SBP
      (beta(s.e.): -2.18(0.63)), P<0.001) only in males, and such associations were
      independent of adiposity and IR. A test of gender * adiponectin interaction was
      significant (P=0.01). Heritability estimation showed that both environmental and
      genetic factors contribute to variance in adipokines. In these relatively lean
      Chinese adolescents, leptin was positively associated with BP in both genders,
      but was adiposity/IR dependent. Adiponectin was negatively associated with SBP in
      males, independent of adiposity/IR.

PMID- 21716318
TI  - The Medical and Endovascular Treatment of Atherosclerotic Renal Artery Stenosis
      (METRAS) study: rationale and study design.
AB  - It is unclear whether revascularization of renal artery stenosis (RAS) by means
      of percutaneous renal angioplasty and stenting (PTRAS) is advantageous over
      optimal medical therapy. Hence, we designed a randomized clinical trial based on
      an optimized patient selection strategy and hard experimental endpoints. Primary
      objective of this study is to determine whether PTRAS is superior or equivalent
      to optimal medical treatment for preserving glomerular filtration rate (GFR) in
      the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan.
      Secondary objectives of this study are to establish whether the two treatments
      are equivalent in lowering blood pressure, preserving overall renal function and
      regressing target organ damage, preventing cardiovascular events and improving
      quality of life. The study is designed as a prospective multicentre randomized,
      un-blinded two-arm study. Eligible patients will have clinical and angio-CT
      evidence of RAS. Inclusion criteria is RAS affecting the main renal artery or its
      major branches either >70% or, if <70, with post-stenotic dilatation. Renal
      function will be assessed with 99mTc-DTPA renal scintigraphy. Patients will be
      randomized to either arms considering both resistance index value in the ischemic
      kidney and the presence of unilateral/bilateral stenosis. Primary experimental
      endpoint will be the GFR of the ischemic kidney, assessed as quantitative
      variable by 99TcDTPA, and the loss of ischemic kidney defined as a categorical
      variable.

PMID- 21716319
TI  - Maternal iNOS genetic polymorphisms and hypertensive disorders of pregnancy.
AB  - Increased expression and activity of inducible nitric oxide synthase (iNOS) may
      contribute to the pathogenesis of pre-eclampsia (PE) and gestational hypertension
      (GH). However, no previous study has examined whether genetic polymorphisms in
      the iNOS gene are associated with PE or GH. We examined whether two functional,
      clinically relevant iNOS genetic polymorphisms (the C(-1026)A polymorphism,
      rs2779249, in the promoter region, and the G2087A polymorphism, rs2297518, in
      exon 16) are associated with GH or with PE. We studied 565 pregnant women: 212
      healthy pregnant (HP), 166 pregnant with GH and 187 pregnant with PE. Genotypes
      were determined by real-time PCR, using the Taqman allele discrimination assay.
      The PHASE 2.1 program was used to estimate haplotype distributions in the three
      study groups. We found no significant association between the C(-1026)A
      polymorphism and PE or GH (P>0.05). However, we found the GA genotype and the A
      allele for the G2087A polymorphism at higher frequency in PE, but not in GH,
      compared with HP (P<0.05). The haplotype analysis showed no significant
      intergroup differences (P>0.05). These findings suggest that iNOS genetic
      variants may affect the susceptibility to PE, but not to GH.

PMID- 21716320
TI  - Development of allele-specific therapeutic siRNA for keratin 5 mutations in
      epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is an incurable, inherited skin-blistering
      disorder predominantly caused by dominant-negative mutations in the genes
      encoding keratins K5 or K14. RNA interference, particularly in the form of small
      interfering RNA (siRNA), offers a potential therapy route for EBS and related
      keratin disorders by selectively silencing the mutant allele. Here, using a
      systemic screening system based on a luciferase reporter gene assay, we have
      developed mutant-specific siRNAs for two independent EBS-causing missense
      mutations in the K5 gene (p.Ser181Pro and p.Asn193Lys). The specificity of the
      allele-specific inhibitors identified in the screen was subsequently confirmed at
      the protein level, where the lead inhibitors were shown to strongly knock down
      the expression of mutant proteins with negligible effect on wild-type K5
      expression. In a cell-based model system, the lead inhibitors were able to
      significantly reverse the cytoskeletal aggregation phenotype. Overall, this
      approach shows promise for the treatment of EBS and paves the way for future
      clinical trials.

PMID- 21716321
TI  - Serum levels of inhibitors of apoptotic proteins (IAPs) change with IVIg therapy
      in pemphigus.

PMID- 21716322
TI  - Inhibition of contact sensitivity by farnesylthiosalicylic acid-amide, a
      potential Rap1 inhibitor.
AB  - We hypothesized that Ras proximate 1 (Rap1) functions as an additional target for
      farnesylthiosalicylic acid (FTS) or its derivatives, and that the inhibition of
      Rap1 in lymphocytes by these agents may represent a method for treating
      inflammatory disorders. Indeed, we found that FTS-amide (FTS-A) was able to
      inhibit the elicitation phase of delayed cutaneous hypersensitivity in vivo. This
      effect was associated with the inhibition of Rap1 more than with the inhibition
      of Harvey rat sarcoma viral oncogene (Ras). Moreover, FTS-A inhibited Rap1 and
      contact sensitivity far better than FTS. We suggest that FTS-A may serve as a
      possible therapeutic tool in contact sensitivity in particular and T-cell
      mediated inflammation in general.

PMID- 21716323
TI  - The G60S connexin43 mutant regulates hair growth and hair fiber morphology in a
      mouse model of human oculodentodigital dysplasia.
AB  - Patients expressing mutations in the gene encoding the gap junction protein Cx43
      suffer from a disease called oculodentodigital dysplasia (ODDD). Patients with
      ODDD are often reported to develop hair that is dry, dull, sparse, and slow
      growing. To evaluate the linkage between Cx43 and hair growth, structure, and
      follicle density we employed a mouse model of ODDD that harbors a Cx43 G60S point
      mutant. Regionally sparse and overall dull hair were observed in mutant mice
      compared with their wild-type (WT) littermates. However, histological analysis of
      overall hair follicle density in mutant and WT mice did not reveal any
      significant differences. After epilation, mutant mouse hair grew back slower, and
      hair growth was asynchronous. In addition, ultrastructural scanning electron
      microscopic imaging of hair fibers taken from mutant mice and two patients
      harboring the G143S mutation revealed severe cuticle weathering. Nodule formation
      was also observed in the proximal region of hair fibers taken from mutant mice.
      These results suggest that the G60S mutant mouse model mimics the hair phenotype
      found in at least some ODDD patients and suggests an important role for Cx43 in
      hair regeneration, growth, and cuticle formation.

PMID- 21716324
TI  - Extracellular double-stranded RNA induces TSLP via an endosomal acidification-
      and NF-kappaB-dependent pathway in human keratinocytes.
AB  - Double-stranded RNA (dsRNA) causes keratinocytes to release thymic stromal
      lymphopoietin (TSLP), which plays a key role in allergic diseases. Endosomal Toll
      like receptor 3 (TLR3) and cytosolic RIG-like receptors (RLRs) and PKR have been
      reported to recognize dsRNA. Here, we demonstrate that dsRNA induces TSLP in
      keratinocytes via an endosomal acidification-dependent and NF-kappaB-mediated
      pathway. After treatment with pharmacologic inhibitors or transfection with small
      interfering RNAs (siRNAs), primary human keratinocytes were stimulated.
      Bafilomycin A1, which inhibits endosomal acidification to block the TLR3 pathway,
      blocked the dsRNA-induced expression of TSLP, IL-8, IFN-beta, and other molecules
      including the dsRNA sensors, whereas it did not inhibit diacyllipopeptide-induced
      expression of TSLP and IL-8. The dsRNA-induced gene expression of TSLP depended
      on RelA, a component of NF-kappaB, but not IRF3, similar to IL-8 but different
      from IFN-beta, which depended on both IRF3 and RelA. The results indicate that
      endosomal acidification and the subsequent activation of NF-kappaB are necessary
      to sense extracellular dsRNA, suggesting the importance of the TLR3-NF-kappaB
      axis to trigger production of TSLP against the self dsRNA released from damaged
      cells or viral dsRNA, in the epidermis, relating to skin inflammation including
      atopic dermatitis (AD).

PMID- 21716325
TI  - Lamellar lipid organization and ceramide composition in the stratum corneum of
      patients with atopic eczema.

PMID- 21716326
TI  - Suppression of E-cadherin function drives the early stages of Ras-induced
      squamous cell carcinoma through upregulation of FAK and Src.
AB  - Advanced stages of epithelial carcinogenesis involve the loss of intercellular
      adhesion, but it remains unclear how proteins that regulate alterations in cell
      cell and cell-matrix adhesion are deregulated to promote the early stages of
      cancer development. To address this, a three-dimensional human tissue model that
      mimics the incipient stages of squamous cell carcinoma (SCC) was used to study
      how E-cadherin suppression promotes tumor progression in Ras-expressing human
      keratinocytes. We found that E-cadherin suppression triggered elevated mRNA and
      protein expression levels of focal adhesion kinase (FAK), and increased FAK and
      Src activities above the level seen in Ras-expressing E-cadherin-competent
      keratinocytes. The short hairpin RNA (shRNA)-mediated depletion of FAK and Src
      restored E-cadherin expression levels by increasing its stability in the
      membrane, and blocked tumor cell invasion in tissues. Surface transplantation of
      these tissues to mice resulted in reversion of the tumor phenotype to low-grade
      tumor islands in contrast to control tissues that manifested an aggressive, high
      grade SCC. These findings suggest that the tumor-promoting effect of E-cadherin
      suppression, a common event in SCC development, is exacerbated by enhanced E
      cadherin degradation induced by elevated FAK and Src activities. Furthermore,
      they imply that targeting FAK or Src in human epithelial cells with neoplastic
      potential may inhibit the early stages of SCC.

PMID- 21716327
TI  - Inflammation and hypertension: the interplay of interleukin-6, dietary sodium,
      and the renin-angiotensin system in humans.
AB  - BACKGROUND: Prior evidence suggests a link between inflammation and hypertension.
      Interleukin-6 (IL-6) has been implicated in animal studies to play an important
      role in angiotensin II (ANGII)-mediated hypertension. The aim of this study was
      to examine the relationship of IL-6 and renin-angiotensin system (RAS) activity
      in human hypertension. METHODS: Data from 385 hypertensives and 196 normotensives
      are included in this report. Blood pressure and laboratory evaluation were
      performed on liberal and low sodium diets. IL-6 response to an ANGII infusion was
      evaluated to assess the effect of acute RAS activation. RESULTS: Hypertensives
      had higher baseline IL-6 and C-reactive protein (CRP) compared with normotensives
      on both diets. IL-6 increased in response to ANGII in hypertensives and
      normotensives (28% in hypertensives, 31% in normotensives, P <= 0.001 for change
      from baseline). In the setting of RAS activation by a low salt diet, multivariate
      regression analysis adjusted for age, body mass index (BMI), gender, race, and
      hypertension status demonstrated an independent positive association of plasma
      renin activity (PRA) with CRP (beta = 0.199, P < 0.001). There was no significant
      difference in IL-6 or CRP levels between liberal and low sodium diets.
      CONCLUSION: These findings confirm an association between hypertension and
      inflammation and provide human data supporting previous evidence from animal
      studies that IL-6 plays a role in ANGII-mediated hypertension. Notably, compared
      to levels on a liberal sodium diet, neither IL-6 nor CRP were higher with
      activation of the RAS by a low salt diet indicating that a low sodium diet is not
      inflammatory despite increased RAS activity.

PMID- 21716328
TI  - Vitamin D and racial disparity in albuminuria: NHANES 2001-2006.
AB  - BACKGROUND: National data show unexplained racial disparity in albuminuria. We
      assessed whether low serum vitamin D status contributes to racial disparity in
      albuminuria. METHODS: We examined the association between race and albuminuria
      (spot urinary albumin/creatinine ratio (ACR) >=30) among non-Hispanic black and
      white nonpregnant adults who were free of renal impairment in the National Health
      and Nutrition Examination Survey (NHANES) from 2001-2006. We conducted analyses
      without and with serum 25(OH)D. We adjusted for age, sex, education level,
      smoking, body mass index (BMI), diabetes, diagnosis of hypertension, and use of
      antihypertensive medication. RESULTS: Albuminuria was present in 10.0% of non
      Hispanic blacks and 6.6% in non-Hispanic whites. Being black (odds ratio (OR)
      1.46; 95% confidence interval (CI) 1.23-1.73) was independently associated with
      albuminuria. There was a graded, inverse association between 25(OH)D level and
      albuminuria. Notably, the association between race and albuminuria was no longer
      significant (OR 1.19; 95% CI 0.97-1.47) after accounting for participants' serum
      25(OH)D. Similar results were observed when participants with macroalbuminuria
      (ACR >=300 mg/g) or elevated parathyroid hormone (>74 pg/ml) were excluded or
      when a continuous measure of 25(OH)D was substituted for the categorical measure.
      There were no interactions between race and vitamin D status though racial
      disparity in albuminuria was observed among participants with the highest 25(OH)D
      levels . CONCLUSION: Suboptimal vitamin D status may contribute to racial
      disparity in albuminuria. Randomized controlled trials are needed to determine
      whether supplementation with vitamin analogues reduces risk for albuminuria or
      reduce racial disparity in this outcome.

PMID- 21716330
TI  - Design and fabrication of optical system for time-multiplex autostereoscopic
      display.
AB  - We propose and experimentally demonstrate a novel time-multiplexed
      autostereoscopic multi-view full resolution 3D display based on the lenticular
      lens array in association with the control of the active dynamic LED backlight.
      The lenticular lenses of the lens array optical system receive the light and
      deflect the light into each viewing zone in a time sequence.

PMID- 21716329
TI  - Angiotensin II shifts insulin signaling into vascular remodeling from glucose
      metabolism in vascular smooth muscle cells.
AB  - BACKGROUND: To clarify the role of angiotensin II (Ang II) in insulin-induced
      arteriosclerosis, we examined the effects of Ang II on insulin-induced mitogen
      activated protein (MAP) kinase activation and cellular hypertrophy in rat
      vascular smooth muscle cells (VSMCs). METHODS: Phosphorylated MAP kinases were
      detected with western blot analysis. Cellular hypertrophy and glucose uptake were
      evaluated from incorporation of [(3)H]-labeled-leucine and -deoxy-D-glucose,
      respectively. Cell sizes were measured by Coulter counter. RESULTS: While Ang II
      (100 nmol/l, 18 h) augmented cellular hypertrophy by insulin (10 nmol/l, 24 h),
      insulin alone did not affect hypertrophy without Ang II pretreatment. Insulin
      increased p38MAP kinase and c-Jun N-terminal kinase (JNK) phosphorylation; in the
      presence of Ang II, p38MAP kinase, and JNK were further activated by insulin.
      Treatment of a p38MAP kinase inhibitor, SB203580 (10 umol/l), and a JNK
      inhibitor, SP600125 (20 umol/l), abrogated the [(3)H]-leucine incorporation by
      insulin in the presence of Ang II. Both the Ang II receptor blocker, RNH-6270
      (100 nmol/l), and an antioxidant, ebselen (40 umol/l), inhibited vascular cell
      hypertrophy. Specific depletion of insulin receptor substrate-1 with small
      interfering RNA increased [(3)H]-leucine incorporation by insulin (10 nmol/l, 24
      h); pretreatment with Ang II attenuated insulin (10 nmol/l, 30 min)-induced
      glucose uptake. CONCLUSIONS: Ang II attenuates insulin-stimulated glucose uptake
      and enhances vascular cell hypertrophy via oxidative stress- and MAP kinase
      mediated pathways in VSMCs. Ang II may also cause insulin signaling to diverge
      from glucose metabolism into vascular remodeling, affecting insulin-induced
      arteriosclerosis in hypertension.

PMID- 21716331
TI  - Reconfigurable quantum metamaterials.
AB  - By coupling controllable quantum systems into larger structures we introduce the
      concept of a quantum metamaterial. Conventional meta-materials represent one of
      the most important frontiers in optical design, with applications in diverse
      fields ranging from medicine to aerospace. Up until now however, metamaterials
      have themselves been classical structures and interact only with the classical
      properties of light. Here we describe a class of dynamic metamaterials, based on
      the quantum properties of coupled atom-cavity arrays, which are intrinsically
      lossless, reconfigurable, and operate fundamentally at the quantum level. We show
      how this new class of metamaterial could be used to create a reconfigurable
      quantum superlens possessing a negative index gradient for single photon imaging.
      With the inherent features of quantum superposition and entanglement of
      metamaterial properties, this new class of dynamic quantum metamaterial, opens a
      new vista for quantum science and technology.

PMID- 21716332
TI  - Dark and bright localized surface plasmons in nanocrosses.
AB  - A metallic nanocross geometry sustaining broad dipole and sharp higher order
      localized surface plasmon resonances is investigated. Spectral tunability is
      achieved by changing the cross arm length and the angle between the arms. The
      degree of rotational symmetry of the nanocross is varied by adding extra arms,
      changing the arm angle and shifting the arm intersection point. The particle's
      symmetry is shown to have a crucial influence on the plasmon coupling to incident
      radiation. Pronounced dipole, quadrupole, octupole and Fano resonances are
      observed in individual cross structures. Furthermore, the nanocross geometry
      proves to be a useful building block for coherently coupled plasmonic dimers and
      trimers where the reduced symmetry results in hybridized subradiant and
      superradiant modes and multiple Fano interferences. Finite difference time domain
      calculations of absorption and scattering cross-sections as well as charge
      density profiles are used to reveal the nature of the different plasmon modes.
      Experimental spectra for the discussed geometries support the calculations.

PMID- 21716333
TI  - Application of linear Raman spectroscopy for the determination of acetone
      decomposition.
AB  - Acetone (CH<sub>3</sub>)<sub>2</sub>CO is a common tracer for laser-induced
      fluorescence (LIF) to investigate mixture formation processes and temperature
      fields in combustion applications. Since the fluorescence signal is a function of
      temperature and pressure, calibration measurements in high pressure and high
      temperature cells are necessary. However, there is a lack of reliable data of
      tracer stability at these harsh conditions for technical application. A new
      method based on the effect of spontaneous Raman scattering is proposed to analyze
      the thermal stability of the tracer directly in the LIF calibration cell. This is
      done by analyzing the gas composition regarding educts and products of the
      reaction. First measurements at IC engine relevant conditions up to 750 K and 30
      bar are presented.

PMID- 21716334
TI  - X-ray holographic microscopy with zone plates applied to biological samples in
      the water window using 3rd harmonic radiation from the free-electron laser FLASH.
AB  - The imaging of hydrated biological samples - especially in the energy window of
      284-540 eV, where water does not obscure the signal of soft organic matter and
      biologically relevant elements - is of tremendous interest for life sciences.
      Free-electron lasers can provide highly intense and coherent pulses, which allow
      single pulse imaging to overcome resolution limits set by radiation damage. One
      current challenge is to match both the desired energy and the intensity of the
      light source. We present the first images of dehydrated biological material
      acquired with 3rd harmonic radiation from FLASH by digital in-line zone plate
      holography as one step towards the vision of imaging hydrated biological material
      with photons in the water window. We also demonstrate the first application of
      ultrathin molecular sheets as suitable substrates for future free-electron laser
      experiments with biological samples in the form of a rat fibroblast cell and
      marine biofouling bacteria Cobetia marina.

PMID- 21716335
TI  - Bright green-emitting, energy transfer and quantum cutting of Ba3Ln(PO4)3: Tb3+
      (Ln = La, Gd) under VUV-UV excitation.
AB  - Tb3+ doped Ba3Gd(PO4)3 and Ba3La(PO4)3 phosphors were synthesized using the
      traditional high temperature solid state reaction method. The excitation,
      emission, and decay spectra were measured at room temperature. Efficient energy
      transfer (ET) from Gd3+ to Tb3+ exists in Tb3+ doped Ba3Gd(PO4)3, and the ET
      efficiency increases with the increase of Tb3+ concentration. The visible quantum
      cutting (QC) via cross relaxation was observed upon exciting low-spin (7D(J)) 5d
      levels of Tb3+ ions. Ba3Tb(PO4)3 sample shows relatively strong emission
      intensity in comparison with Zn2SiO4: Mn2+ (ZSM) upon 172 nm excitation, and with
      a decay time tau(1/10) about 6.4 ms under 351 nm excitation, indicating the
      potential application of this phosphor for plasma display panels (PDPs) and Hg
      free lamps.

PMID- 21716336
TI  - Demonstration of two-dimensional photonic crystals based on silicon carbide.
AB  - We demonstrate two-dimensional photonic crystals of silicon carbide (SiC)-a wide
      bandgap semiconductor and one of the hardest materials-at near-infrared
      wavelengths. Although the refractive index of SiC is lower than that of a
      conventional semiconductor such as GaAs or Si, we show theoretically that a wide
      photonic bandgap, a broadband waveguide, and a high-quality nanocavity comparable
      to those of previous photonic crystals can be obtained in SiC photonic crystals.
      We also develop a process for fabricating SiC-based photonic crystals that
      experimentally show a photonic bandgap of 200 nm, a waveguide with a 40-nm
      bandwidth, and a nanocavity with a high quality factor of 4,500. This
      demonstration should stimulate further development of resilient and stable
      photonics at high power and high temperature analogous to SiC power electronics.

PMID- 21716337
TI  - Long range surface plasmon-coupled fluorescence emission for biosensor
      applications.
AB  - A biosensor scheme that employs long range surface plasmons (LRSPs) for the
      efficient excitation and collection of fluorescence light from fluorophore
      labeled biomolecules captured in a three-dimensional hydrogel matrix is
      discussed. This new approach to plasmon-enhanced fluorescence (PEF) is
      experimentally and theoretically investigated by using the Kretschmann
      configuration of attenuated total reflection (ATR) method. A layer structure
      supporting LRSPs that consists of a low refractive index fluoropolymer layer, a
      thin gold film and a large binding capacity N-isopropylacrylamide (NIPAAm)-based
      hydrogel matrix swollen in an aqueous sample is employed. By using this layer
      architecture, the extended field of LRSPs probes the binding of biomolecules in
      the binding matrix at up to micrometer distances from the gold surface. With
      respect to regular surface plasmon-enhanced fluorescence spectroscopy (SPFS) and
      surface plasmon-coupled emission (SPCE), a narrower angular distribution of the
      fluorescence light intensity, a larger peak intensity and the excitation and
      emission at lower angles were observed.

PMID- 21716338
TI  - Ultra-dense WDM-PON delivering carrier-centralized Nyquist-WDM uplink with
      digital coherent detection.
AB  - We introduce an "ultra-dense" concept into next-generation WDM-PON systems, which
      transmits a Nyquist-WDM uplink with centralized uplink optical carriers and
      digital coherent detection for the future access network requiring both high
      capacity and high spectral efficiency. 80-km standard single mode fiber (SSMF)
      transmission of Nyquist-WDM signal with 13 coherent 25-GHz spaced wavelength
      shaped optical carriers individually carrying 100-Gbit/s polarization
      multiplexing quadrature phase-shift keying (PM-QPSK) upstream data has been
      experimentally demonstrated with negligible transmission penalty. The 13
      frequency-locked wavelengths with a uniform optical power level of -10 dBm and
      OSNR of more than 50 dB are generated from a single lightwave via a multi-carrier
      generator consists of an optical phase modulator (PM), a Mach-Zehnder modulator
      (MZM), and a WSS. Following spacing the carriers at the baud rate, sub-carriers
      are individually spectral shaped to form Nyquist-WDM. The Nyquist-WDM channels
      have less than 1-dB crosstalk penalty of optical signal-to-noise ratio (OSNR) at
      2 * 10(-3) bit-error rate (BER). Performance of a traditional coherent optical
      OFDM scheme and its restrictions on symbol synchronization and power difference
      are also experimentally compared and studied.

PMID- 21716339
TI  - Observation of spontaneous polarization misalignments in periodically poled
      crystals using second-harmonic generation microscopy.
AB  - Periodically poled crystal (PPC) is a key component for nonlinear optical
      applications. Its poling quality relies largely on successful domain inversion
      and the alignment of spontaneous polarization (SP) vectors in each domain. Here
      we report the unexpected observation of bulk second harmonic generation (SHG) in
      PPC when excitation propagating along its optical axis. Based on its tensorial
      nature, SHG is highly sensitive to the orientation of SP, and therefore the
      misalignment of SP in each domain of PPC can be revealed noninvasively by SHG
      microscopy. This nonlinear imaging modality provides optical sectioning
      capability with 3D sub-micrometer resolution, so it will be useful for in situ
      investigation of poling quality in PPC.

PMID- 21716340
TI  - Arbitrarily thin metamaterial structure for perfect absorption and giant
      magnification.
AB  - In our common understanding, for strong absorption or amplification in a slab
      structure, the desire of reducing the slab thickness seems contradictory to the
      condition of small loss or gain. In this paper, this common understanding is
      challenged. It is shown that an arbitrarily thin metamaterial layer can perfectly
      absorb or giantly amplify an incident plane wave at a critical angle when the
      real parts of the permittivity and permeability of the metamaterial are zero
      while the absolute imaginary parts can be arbitrarily small. The metamaterial
      layer needs a totally reflective substrate for perfect absorption, while this is
      not required for giant magnification. Detailed analysis for the existence of the
      critical angle and physical explanation for these abnormal phenomena are given.

PMID- 21716341
TI  - High efficiency nano-focusing kinoform optics for synchrotron radiation.
AB  - Modern synchrotron sources have provided for decades intense beams of photons
      over a large energy spectrum. The availability of improved optics and detectors
      has opened up new opportunities for the study of matter at the micrometre and
      nanometre scale in many disciplines. Whilst exploitation of micro-focused beams
      occurs almost daily in many beamlines, the production of beams of 100 nm is
      achieved on few instruments which use specialised optics. Refractive lenses, zone
      plates, curved mirrors, multilayers, and multilayer Laue lenses, can all focus x
      rays to less than 50 nm under strict beam stability conditions. Focusing the
      synchrotron radiation to beam sizes smaller than 10 nm is considered the ultimate
      goal for the current decade. Silicon micro-technology has so far provided some of
      the most advanced x-ray refractive lenses; we report on design and
      characterisation of a novel silicon kinoform lens that is capable of delivering
      nano-beams with high efficiency.

PMID- 21716342
TI  - Discrimination of one-photon and two-photon coherence parts in
      electromagnetically induced transparency for a ladder-type three-level atomic
      system.
AB  - We present discrimination of the effect of one-photon and two-photon coherences
      in electromagnetically induced transparency for a three-level ladder-type atomic
      system. After the optical Bloch equations for a three-level atom, with either
      cycling or non-cycling transitions, were solved numerically, the solutions were
      averaged over the velocity distribution and finite transit time. Through this we
      were able to discriminate one-photon and two-photon coherence parts of the
      calculated spectra. We also found that the spectra showed peaks as the branching
      ratio of the intermediate (excited) state increased (decreased). The experimental
      results of previous reports [H. S. Moon, et al., Opt. Express 16, 12163 (2008);
      H. S. Moon and H. R. Noh, J. Phys. B 44, 055004 (2011)] could well be accounted
      for by this discrimination of one-photon and two-photon coherences in the
      transmittance signals for the simplified three-level atomic system.

PMID- 21716343
TI  - Modeling optical properties of particles with small-scale surface roughness:
      combination of group theory with a perturbation approach.
AB  - A T-matrix method for scattering by particles with small-scale surface roughness
      is presented. The method combines group theory with a perturbation expansion
      approach. Group theory is found to reduce CPU-time by 4-6 orders of magnitude.
      The perturbation expansion extends the range of size parameters by a factor of 5
      compared to non-perturbative methods. An application to optically hard particles
      shows that small-scale surface roughness changes scattering in side- and
      backscattering directions, and it impacts the single-scattering albedo. This can
      have important implications for interpreting remote sensing observations, and for
      the climate impact of mineral aerosols.

PMID- 21716344
TI  - High-efficiency, multicrystal, single-pass, continuous-wave second harmonic
      generation.
AB  - We describe the critical design parameters and present detailed experimental and
      theoretical studies for efficient, continuous-wave (cw), single-pass second
      harmonic generation (SHG) based on novel cascaded multicrystal scheme, providing
      >55% conversion efficiency and multiwatt output powers at 532 nm for a wide range
      of input fundamental powers at 1064 nm. Systematic characterization of the
      technique in single-crystal, double-crystal and multicrystal schemes has been
      performed and the results are compared. Optimization of vital parameters
      including focusing and phase-matching temperature at the output of each stage is
      investigated and strategies to achieve optimum SHG efficiency and power are
      discussed. Relevant theoretical calculations to estimate the effect of dispersion
      between the fundamental and the SH beam in air are also presented. The
      contributions of thermal effects on SHG efficiency roll-off have been studied
      from quasi-cw measurements. Using this multicrystal scheme, stable SH power with
      a peak-to-peak fluctuation better than 6.5% over more than 2 hours is achieved in
      high spatial beam quality with M2<1.6.

PMID- 21716345
TI  - Influence of the higher-orders of diffraction on the pattern evolution for
      tightly focused beams.
AB  - The mechanism of the nonparaxial propagation for tightly focused beams is
      investigated in the view of the influence of the higher-orders of diffraction
      (HOD). The HOD induce novel propagation characteristics which are crucially
      different from those predicted by the traditional paraxial theory. Based on the
      management of HOD, we propose an approach on controlling the intensity pattern of
      the focus to satisfy the application requirements.

PMID- 21716346
TI  - Experimental demonstration of gridless spectrum and time optical switching.
AB  - An experimental demonstration of gridless spectrum and time switching is
      presented. We propose and demonstrate a bit-rate and modulation-format
      independent optical cross-connect architecture, based on gridless spectrum
      selective switch, 20-ms 3D-MEMS and 10-ns PLZT optical switches, that supports
      arbitrary spectrum allocation and transparent time multiplexing. The architecture
      is implemented in a four-node field-fiber-linked testbed to transport continuous
      RZ and NRZ data channels at 12.5, 42.7 and 170.8 Gb/s, and selectively groom sub
      wavelength RZ channels at 42.7 Gb/s. We also showed that the architecture is
      dynamic and can be reconfigured to meet the routing requirements of the network
      traffic. Results show error-free operation with an end-to-end power penalty
      between 0.8 dB and 5 dB for all continuous and sub-wavelength channels.

PMID- 21716347
TI  - Electro-optic thin films of organic nonlinear optic molecules aligned through
      vacuum deposition.
AB  - Nonlinear optical molecules can be vacuum deposited into uniform thin films using
      thermal evaporation. Alignment order can be achieved during thin film deposition
      by an in-plane electrical field poling using electrodes patterned on the
      substrate. Electro-optic (EO) coefficients, r33 and r13 are independently
      measured using Young's interferometry technique. Thin-films of N-benzyl-2-methyl
      4-nitroaniline (BNA) can exhibit an EO coefficient, r33, comparable to that of
      BNA single crystals. EO coefficients of BNA at different poling fields,
      wavelengths, and frequencies are investigated.

PMID- 21716348
TI  - Pump power dependence of femtosecond two-color optical Kerr shutter measurements.
AB  - We investigated the pump power dependence of femtosecond two-color optical Kerr
      shutter (OKS) signals, which showed a damped sinusoidal variation with increasing
      pump power. The sinusoidal dependence was attributed to the polarization rotation
      caused by light-induced birefringence effect. The numerical analysis indicated
      that, the damping of OKS signal intensity could be attributed to the temporal
      profile change of probe pulse passing through the OKS setup, due to the non
      uniform transient refractive index change induced by pump pulse. Because of the
      large phase shift of probe pulse, the time-resolved OKS signals showed modulated
      temporal intensity when pump power was increased.

PMID- 21716349
TI  - Angle-and polarization-dependent collective excitation of plasmonic nanoarrays
      for surface enhanced infrared spectroscopy.
AB  - Our recent work has showed that diffractively coupled nanoplasmonic arrays for
      Fourier transform infrared (FTIR) microspectroscopy can enhance the Amide I
      protein vibrational stretch by up to 10(5) times as compared to plain substrates.
      In this work we consider computationally the impact of a microscope objective
      illumination cone on array performance. We derive an approach for computing
      angular- and spatially-averaged reflectance for various numerical aperture (NA)
      objectives. We then use this approach to show that arrays that are perfectly
      optimized for normal incidence undergo significant response degradation even at
      modest NAs, whereas arrays that are slightly detuned from the perfect grating
      condition at normal incidence irradiation exhibit only a slight drop in
      performance when analyzed with a microscope objective. Our simulation results are
      in good agreement with microscope measurements of experimentally optimized
      periodic nanoplasmonic arrays.

PMID- 21716350
TI  - Simultaneous ranging and velocimetry of fast moving targets using oppositely
      chirped pulses from a mode-locked laser.
AB  - A lidar system based on the coherent detection of oppositely chirped pulses
      generated using a 20 MHz mode locked laser and chirped fiber Bragg gratings is
      presented. Sub millimeter resolution ranging is performed with > 25 dB signal to
      noise ratio. Simultaneous, range and Doppler velocity measurements are
      experimentally demonstrated using a target moving at > 330 km/h inside the
      laboratory.

PMID- 21716351
TI  - Thermo-optical tunable planar ridge microdisk resonator in silicon-on-insulator.
AB  - In this work, we design and demonstrate planar ridge microdisk resonators in
      silicon-on-insulator, which assemble the advantages of microring and microdisk
      resonators. The dependences of resonator optical modes on the slab thickness and
      the waveguide-to-resonator coupling gap are investigated. The highest Q-factor
      obtained is ~4 * 10(5). Using the thermo-optical effect, we attain a resonance
      wavelength tuning efficiency of ~66.5 pm/mW. We also compare the transmission
      spectra measured by using wavelength-scanning method and voltage-scanning method
      and show potential application for the adopted voltage-scanning method.

PMID- 21716352
TI  - Single-shot terahertz spectroscopy using pulse-front tilting of an ultra-short
      probe pulse.
AB  - We developed a single-shot terahertz pulse measurement technique using pulse
      front tilting of an ultra-short probe pulse and demonstrated single-shot
      terahertz spectroscopy. A transmission grating was used to introduce a
      sufficiently large pulse-front tilt angle. A measuring time range of 23.8 ps was
      achieved. The measured temporal waveforms were corrected in consideration of the
      nonlinearity arising from the crossed-Nicols arrangement employed and the beam
      profiles of the probe and terahertz pulses. The characteristic spectrum of
      lactose was measured with a single terahertz pulse, and the effectiveness of our
      single-shot technique was confirmed by comparison with a conventional sampling
      method.

PMID- 21716353
TI  - Transverse electric plasmons in bilayer graphene.
AB  - We predict the existence of transverse electric (TE) plasmons in bilayer
      graphene. We find that their plasmonic properties are much more pronounced in
      bilayer than in monolayer graphene, in a sense that they can get more localized
      at frequencies just below homega = 0.4 eV for adequate doping values. This is a
      consequence of the perfectly nested bands in bilayer graphene which are separated
      by ~ 0.4 eV.

PMID- 21716354
TI  - Nonlinear atom-field dynamics in high-Q cavities: from a BEC to a thermal gas.
AB  - A cold gas of polarizable particles moving in the optical potential of a standing
      wave high finesse optical resonator acts as a dynamic refractive index. For a
      sufficiently strong cavity pump the optical forces generated by the intra cavity
      field perturb the particles phase space distribution, which shifts the optical
      resonance frequency and induces a nonlinear optical response. By help of the
      corresponding Vlasov equation we predict that beyond the known phenomenon of
      optical bi-stability one finds regions in parameter space, where no stable
      stationary solution exists. The atom field dynamics then exhibits oscillatory
      solutions converging to stable limit cycles of the system. The linearized
      analytical predictions agree well with corresponding numerical solutions of the
      full time dependent equations and first experimental observation in both cases.

PMID- 21716355
TI  - Enhancing solar cells with localized plasmons in nanovoids.
AB  - Localized plasmon resonances of spherical nanovoid arrays strongly enhance solar
      cell performance by a factor of 3.5 in external quantum efficiency at plasmonic
      resonances, and a four-fold enhancement in overall power conversion efficiency.
      Large area substrates of silver nanovoids are electrochemically templated through
      self-assembled colloidal spheres and organic solar cells fabricated on top. Our
      design represents a new class of plasmonic photovoltaic enhancement: that of
      localized plasmon-enhanced absorption within nanovoid structures. Angularly
      resolved spectra demonstrate strong localized Mie plasmon modes within the
      nanovoids. Theoretical modelling shows varied spatial dependence of light
      intensity within the void region suggesting a first possible route towards Third
      Generation plasmonic photovoltaics.

PMID- 21716356
TI  - Data transmission by hypergeometric modes through a hyperbolic-index medium.
AB  - We study the existence of a novel complete family of exact and orthogonal
      solutions of the paraxial wave equation. The complex amplitude of these beams is
      proportional to the confluent hypergeometric function, which we name
      hypergeometric modes of type-II (HyG-II). It is formally demonstrated that
      hyperbolic-index medium can generate and support the propagation of such a class
      of beams. Since these modes are eigenfunctions of the photon orbital angular
      momentum, we conclude that an optical fiber with hyperbolic-index profile could
      take advantage over other graded-index fibers by the capacity of data
      transmission.

PMID- 21716357
TI  - ZnO-coated CuO nanowire arrays: fabrications, optoelectronic properties, and
      photovoltaic applications.
AB  - We report a growth of p-CuO nanowire arrays with a simple thermal oxidation and a
      fabrication of nanowire-based heterojunctions by coating the p-CuO nanowire
      arrays in an n-ZnO layer through a thermal decomposition method. Their
      optoelectronic properties and photovoltaic performance were investigated.
      Compared with the conductance in the dark, a 154% increase in photoconductance
      was obtained under a white light illumination of 100 mW/cm2. The heterojunctions
      exhibit an obvious photocurrent increment of 0.264 mA under the illumination of
      141 mW/cm2. After annealing the heterojunctions at 100 degrees C for 25 min, a
      larger open-circuit voltage of 0.37 V was obtained, the short-circuit current
      density increase to 0.63 mA/cm2 from original 0.49 mA/cm2. The overall power
      conversion efficiency is 0.1%.

PMID- 21716358
TI  - A nanoplasmonic probe for near-field imaging.
AB  - We demonstrate a nanoplasmonic probe that incorporates a subwavelength aperture
      coupled to a fine probing tip. This probe is used in a hybrid near-field scanning
      optical microscope and atomic force microscope system that can simultaneously map
      the optical near-field and the topography of nanostructures. By spatially
      isolating but optically coupling the aperture and the localizing point, we
      obtained near-field images at a resolution of 45 nm, corresponding to lambda/14.
      This nanoplasmonic probe design overcomes the resolution challenges of
      conventional apertured near-field optical probes and can provide substantially
      higher resolution than demonstrated in this work.

PMID- 21716359
TI  - An alternative differential method of femtosecond pump-probe examination of
      materials.
AB  - We describe an alternative method for femtosecond pump-probe beam examination of
      energy transport properties of materials. All already reported techniques have
      several drawbacks which limit precise measurements of reflection coefficient as
      function of time. A typical problem is present when rough samples are being
      studied. In this case the pump-beam polarization changes randomly which may
      produce a spurious signal, drastically reducing the signal to noise ratio. Some
      proposals to alleviate such problem have been reported, however, they have not
      been totally satisfactory. The method presented here consists on measuring the
      difference between the two delays' signals of the probe-beam. As will be
      explained, our proposal is free of typical drawbacks. We also propose a numerical
      method to recover the DeltaR(t)/R curve from the measured data. Numerical
      simulations show that our proposal is a viable alternative.

PMID- 21716360
TI  - Sub-wavelength gratings fabricated on a light bar by roll-to-roll UV embossing
      process.
AB  - This research uses a roll-to-roll based ultraviolet (UV) resin process to make
      sub-wavelength gratings for display applications. Based on the rigorous coupling
      wave analysis (RCWA), we analyze the relationship between the first order
      transmission/reflection efficiency and the pitch of the grating for various
      shapes as rays pass through the sub-wavelength gratings, patterned with a
      backlight. The objective is to turn the R/G/B (620 nm, 520 nm, and 450 nm)
      incident rays into uniformly and normally output white light with high
      illuminance from the surface of a light guide.

PMID- 21716361
TI  - Long-reach radio-over-fiber signal distribution using single-sideband signal
      generated by a silicon-modulator.
AB  - The integration of passive optical network (PON) and radio-over-fiber (ROF)
      networks could provide broadband services for both fixed and mobile users in a
      single and low-cost platform. Combining the long-reach (LR)-PON (>100 km) and the
      LR-ROF can further reduce the cost by simplifying the network architecture,
      sharing the same optical components and extending the coverage of ROF network.
      However, the transmission and distribution of ROF signal in LR network is very
      challenging due to the chromatic dispersion generated periodic power fading and
      code time-shifting effects in the optical fiber. In this work, we propose and
      experimentally demonstrate a LR-ROF signal distribution using single-sideband
      (SSB)-ROF signal generated by a silicon ring-modulator. The silicon modulator is
      compact and has low power consumption. Besides, one unique feature of the silicon
      ring-modulator is that it only modulates the signal wavelength at the resonant
      null. This makes it very suitable for the generation of the SSB-ROF signal.
      Numerical comparison of the SSB-ROF with the double-sideband (DSB)-ROF and
      optical carrier suppress (OCS)-ROF signals; as well as the fabrication of the
      silicon ring-modulator will be discussed.

PMID- 21716362
TI  - Mode competition in high power fiber amplifiers.
AB  - Using a beam propagation model of Yb3+ doped, CW fiber amplifiers we show that
      gain saturation by a strong fundamental mode significantly suppresses the growth
      of higher order modes with parallel polarization, but enhances the growth of
      higher order modes with perpendicular polarization. We quantify this effect in
      straight and bent fibers, with full core or restricted area doping.

PMID- 21716363
TI  - Guided mode biosensor based on grating coupled porous silicon waveguide.
AB  - Porous silicon waveguide biosensors that utilize grating couplers etched directly
      into porous silicon are demonstrated for improved molecular detection
      capabilities. Molecules are infiltrated through the grating couplers into the
      waveguide where they can interact with a guided waveguide mode. Hybridization of
      nucleic acids inside the waveguide is shown to significantly perturb the wave
      vector of the guided mode and is detected through angle-resolved reflectance
      measurements. A detection sensitivity of 7.3 degrees /mM is demonstrated with
      selectivity better than 6:1 compared to mismatched sequences. Experimental
      results are in good agreement with calculations based on rigorous coupled wave
      analysis. Use of the all-porous silicon grating-coupled waveguide allows improved
      interaction of the optical field with surface-bound molecules compared to
      evanescent wave-based biosensors.

PMID- 21716364
TI  - Second harmonic generation in multi-domain chi2 media: from disorder to order.
AB  - We investigate systematically the evolution of second harmonic generation in
      strontium barium niobate with different degrees of disorder of its chi2
      nonlinearity. These different degrees of disordered domain structures are
      achieved through electrically switching of the polarization at room temperature.
      The size and distribution of the domains change during the poling process and
      this in turn strongly affects the spatial distribution of the second harmonic
      signal. The degree of disorder can be determined by analyzing the angular
      distribution and wavelength dependence of the second harmonic emission patterns
      combined with measurements of the spontaneous polarization. We demonstrate
      evidence of the control of the second harmonic emission pattern by creating
      defined states of order, and successfully reproduce the resulting patterns
      theoretically.

PMID- 21716365
TI  - Discovery of ordered and quasi-ordered photonic crystal structures in the scales
      of the beetle Eupholus magnificus.
AB  - The outer wing casings (elytra) of the weevil Eupholus magnificus are marked by
      yellow and blue bands. We have investigated the scales covering the elytra by
      using microspectrophotometry, imaging scatterometry, scanning electron microscopy
      and Fourier transform analysis. We demonstrate that the scales in the yellow
      elytral bands comprise highly ordered 3D photonic crystal structures, whereas the
      scales of the blue bands comprise quasi-ordered 3D photonic structures. Both
      systems, highly contrasting in their periodic order, create approximately angle
      independent colour appearances in the far-field. The co-existence of these two
      contrasting forms of 3D structural order in the same single species is certainly
      uncommon in natural biological systems and has not been reported in the photonic
      literature.

PMID- 21716366
TI  - White light Bessel-like beams generated by miniature all-fiber device.
AB  - Micron-sized white light propagation invariant beams generated by a simple and
      compact fiber device are presented. The all-fiber device is fabricated by
      splicing a short piece of large-core multimode fiber onto a small-core single
      mode white light delivery fiber. Because this fiber device offers an inherent
      spatial coherence, nondiffracting white light beams can be created with a
      temporally incoherent broadband light source (a halogen bulb) and, most
      importantly, the surrounding fringes don't fade as the bandwidth of the light
      source increases because the underlying physics of this fiber device is different
      from that of the axicon. White light Bessel-like beams have been generated from
      multimode fibers with core diameters of 50 MUm, 105 MUm, and 200 MUm. The
      distance of nondiffracting propagation of the white light Bessel beam increases
      with increasing core size of the multimode fiber. Propagation characteristics of
      red, green, and blue individual beams are also presented.

PMID- 21716367
TI  - Theoretical and experimental research on designer surface plasmons in a
      metamaterial with double sets of circular holes.
AB  - The designer surface plasmons (DSPs) are studied by the use of a kind of
      metamaterial with a structure of double sets of circular holes: subwavelength
      apertures, and indentations. The diameter and spacing of the indentations are
      smaller at least one order of magnitude than those of the apertures. A
      theoretical model is built to analyze the DSPs sustained by the indentations by
      using effective dipoles method. The influence of the DSPs on the transmission
      property is revealed for electromagnetic waves passing through the apertures. In
      order to verify the theoretical predication, a set of the metamaterial samples is
      made and the transmission spectra are measured in microwave regime. Our results
      provide a new proof for the existence of DSPs and are promising for proposing
      some techniques for optoelectronic devices in terahertz and microwave regime.

PMID- 21716368
TI  - 1.3-MUm InAs/GaAs quantum-dot lasers monolithically grown on Si substrates.
AB  - We report the first operation of an electrically pumped 1.3-MUm InAs/GaAs quantum
      dot laser epitaxially grown on a Si (100) substrate. The laser structure was
      grown directly on the Si substrate by molecular beam epitaxy. Lasing at 1.302 MUm
      has been demonstrated with threshold current density of 725 A/cm2 and output
      power of ~26 mW for broad-area lasers with as-cleaved facets at room temperature.
      These results are directly attributable to the optimized growth temperature of
      the initial GaAs nucleation layer.

PMID- 21716369
TI  - Plasmon delocalization onset in finite sized nanostructures.
AB  - The transition from localized to delocalized plasmons (i.e. the transition from a
      situation where the decay length of a travelling surface plasma wave is greater
      than its propagation distance to a situation where it is smaller) and hence the
      onset of plasmon delocalization is studied in a single 2D silver nanoparticle of
      increasing length. A fourier analysis in the near-field of the nanoparticle is
      used as the main tool for analysis. This method, along with far-field scattering
      spectra simulations and the near-field profile directly above and along the
      length of the nanoparticle are used to investigate and clearly show the
      transition from localized to delocalized modes. In particular, it is found that
      for a finite sized rectangular nanoparticle, both the emerging odd and even
      delocalized modes are nothing but a superposition of many standing wave plasmon
      modes. As a consequence, even very short metal films can support delocalized
      plasmons that bounce back and forth along the film.

PMID- 21716370
TI  - Diffractive optical elements utilized for efficiency enhancement of photovoltaic
      modules.
AB  - Common solar cells used in photovoltaic modules feature metallic contacts which
      partially block the sunlight from reaching the semiconductor layer and reduce the
      overall efficiency of the modules. Diffractive optical elements were generated in
      the bulk glass of a photovoltaic module by ultrafast laser irradiation to direct
      light away from the contacts. Calculations of the planar electromagnetic wave
      diffraction and propagation were performed using the rigorous coupled wave
      analysis technique providing quantitative estimations for the potential
      efficiency enhancement of photovoltaic modules.

PMID- 21716371
TI  - Wavelength-selective addressing of visible and near-infrared plasmon resonances
      for SU8 nanolithography.
AB  - We imprint plasmonic near field enhancements as nanoscale topography in SU8
      photoresist using two-photon absorption from a spectrally filtered broadband
      supercontinuum light source. Imprinted patterns smaller than 50 nm across are
      obtained localized at positions of high local field enhancements in gold bow tie
      antennas, and gold split rings resonant in the visible and near-infrared.
      Enhanced exposure only occurs at wavelengths and polarizations that exactly match
      the plasmonic resonances. Hence our work demonstrates that wavelength selective
      addressing of hot spots for nanolithography using an inexpensive, low peak-power
      picosecond pulsed source is freely tunable throughout the visible and infrared to
      match any desired plasmon resonance.

PMID- 21716372
TI  - Harmonic generation in silicon nitride ring resonators.
AB  - We demonstrate second- and third-harmonic generation in a centrosymmetric CMOS
      compatible material using ring resonators and integrated optical waveguides. The
      chi(2) response is induced by using the nanoscale structure of the waveguide to
      break the bulk symmetry of silicon nitride (Si3N4) with the silicon dioxide
      (SiO2) cladding. Using a high-Q ring resonator cavity to enhance the efficiency
      of the process, we detect the second-harmonic output in the visible wavelength
      range with milliwatt input powers at telecom wavelengths. We also observe third
      harmonic generation from the intrinsic chi(3) susceptibility of the silicon
      nitride. Phase matching of the harmonic processes occurs due to the near
      coincidence of indices of refraction of the fundamental mode at the pump
      frequency and the corresponding higher-order modes of the harmonic fields.

PMID- 21716373
TI  - Light-assisted templated self assembly using photonic crystal slabs.
AB  - We explore a technique which we term light-assisted templated self-assembly. We
      calculate the optical forces on colloidal particles over a photonic crystal slab.
      We show that exciting a guided resonance mode of the slab yields a resonantly
      enhanced, attractive optical force. We calculate the lateral optical forces above
      the slab and predict that stably trapped periodic patterns of particles are
      dependent on wavelength and polarization. Tuning the wavelength or polarization
      of the light source may thus allow the formation and reconfiguration of patterns.
      We expect that this technique may be used to design all-optically reconfigurable
      photonic devices.

PMID- 21716374
TI  - Intensity-based modified Doppler variance algorithm: application to phase
      instable and phase stable optical coherence tomography systems.
AB  - The traditional phase-resolved Doppler method demonstrates great success for in
      vivo imaging of blood flow and blood vessels. However, the phase-resolved method
      always requires high phase stability of the system. In phase instable situations,
      the performance of the phase-resolved methods will be degraded. We propose a
      modified Doppler variance algorithm that is based on the intensity or amplitude
      value. Performances of the proposed algorithm are compared with traditional phase
      resolved Doppler variance and color Doppler methods for both phase stable and
      phase instable systems. For the phase instable situation, the proposed algorithm
      demonstrates images without phase instability induced artifacts. In-vivo imaging
      of window-chamber hamster skin is demonstrated for phase instable situation with
      a spectrometer-based Fourier domain OCT system. A microelectromechanical systems
      (MEMS) based swept source OCT (SSOCT) system is also used to demonstrate the
      performance of the proposed method in a phase instable situation. The phase
      stability of the SSOCT system is analyzed. In-vivo imaging of the blood vessel of
      human skin is demonstrated with the proposed method and the SSOCT system. For the
      phase stable situation, the proposed algorithm also demonstrates comparable
      performance with traditional phase-resolved methods. In-vivo imaging of the human
      choroidal blood vessel network is demonstrated with the proposed method under the
      phase stable situation. Depth-resolved fine choroidal blood vessel networks are
      shown.

PMID- 21716375
TI  - Electrochemically fabricated self-aligned 2-D silver/alumina arrays as reliable
      SERS sensors.
AB  - A novel SERS sensor for adenine molecules is fabricated electrochemically using
      an ordered two-dimensional array of self-aligned silver nanoparticles
      encapsulated by alumina. Silver is electro-deposited on the interior surfaces at
      the bottom of nano-channels in a porous anodic aluminum oxide (AAO) film. After
      etching aluminum, the back-end alumina serves as a SERS substrate. SERS
      enhancement factor greater than 10(6) is measured by 532 nm illumination. It
      exhibits robust chemical stability and emits reproducible Raman signals from
      repetitive uses for eight weeks. The inexpensive mass production process makes
      this reliable, durable and sensitive plasmon based optical device promising for
      many applications.

PMID- 21716376
TI  - Direct laser writing for active and passive high-Q polymer microdisks on silicon.
AB  - We report the fabrication of high-Q polymeric microdisks on silicon via direct
      laser writing utilizing two-photon absorption induced polymerization. The quality
      factors of the passive cavities are above 10(6) in the 1300 nm wavelength region.
      The flexible three-dimensional (3D) lithography method allows for the fabrication
      of different cavity thicknesses on the same substrate, useful for rapid
      prototyping of active and passive optical microcavities. Microdisk lasers are
      realized by doping the resist with dye, resulting in laser emission at visible
      wavelengths.

PMID- 21716377
TI  - Defect solitons in parity-time symmetric superlattices.
AB  - We study defect solitons (DSs) in a parity-time (PT) symmetric superlattice with
      focusing Kerr nonlinearity. The properties of the DSs with a PT symmetrical
      potential are obviously different from those in a superlattice with a real
      refractive index. Unusual features stemming from PT symmetry can be found.
      Research results show that the solitons with a zero defect or a positive defect
      can exist and stably propagate in the semi-infinite gap, but they cannot exist in
      the first gap. For the case of a negative defect, the soliton can stably exist in
      both the semi-infinite gap and the first gap.

PMID- 21716378
TI  - Efficient heterodyne CARS measurement by combining spectral phase modulation with
      temporal delay technique.
AB  - We propose and demonstrate an improved heterodyne coherent anti-Stokes Raman
      scattering (CARS) measurement with a rapid phase modulation and temporal
      displacement of the background, to simplify signal extraction and effectively
      reduce a nonresonant background (NRB). This method is a modification of the
      single-beam CARS spectroscopy originally proposed by Oron et al. in which a
      narrowband phase modulation is used to enhance contrast between resonant signals
      and the NRB through heterodyne detection [Phys. Rev. Lett. 89, 273001 (2002)]. In
      our scheme, a large delay between the narrow- and broadband components enables us
      to reduce the NRB while maintaining signal enhancement by heterodyne detection.
      We develop a frequency-resolved Michelson interferometer in which the narrow- and
      broadband components are spatially separated and recombined with an arbitrary
      delay. We show that sharp Raman lines can be obtained from chloroform molecules
      by the observation of difference spectra and phase sensitive detection. The
      spectral resolution achieved, which is limited by that of the spectrometer we
      used, is < 8 cm(-1). This method can potentially be extended to make real-time
      measurements by further developing a spectrometer that directly accumulates
      difference spectra.

PMID- 21716379
TI  - Light control of silver nanoparticle's diffusion.
AB  - The diffusion of silver nanoparticles in water at 298K inside an optical vortex
      lattice is analyzed in detail by numerical simulations. At power densities of the
      order of those used to trap nanoparticles with optical tweezers, the dynamic
      response shows three different regimes depending on the light wavelength. In the
      first one particles get trapped inside the light vortices following almost closed
      trajectories. In the second one, around the plasmon resonance, the diffusion
      constant is dramatically enhanced with respect to the Brownian motion. In the
      third one, at longer wavelengths, nanoparticles are confined during a few seconds
      in quasi-one-dimensional optical traps.

PMID- 21716380
TI  - Multi-format all-optical processing based on a large-scale, hybridly integrated
      photonic circuit.
AB  - We investigate through numerical studies and experiments the performance of a
      large scale, silica-on-silicon photonic integrated circuit for multi-format
      regeneration and wavelength-conversion. The circuit encompasses a monolithically
      integrated array of four SOAs inside two parallel Mach-Zehnder structures, four
      delay interferometers and a large number of silica waveguides and couplers.
      Exploiting phase-incoherent techniques, the circuit is capable of processing OOK
      signals at variable bit rates, DPSK signals at 22 or 44 Gb/s and DQPSK signals at
      44 Gbaud. Simulation studies reveal the wavelength-conversion potential of the
      circuit with enhanced regenerative capabilities for OOK and DPSK modulation
      formats and acceptable quality degradation for DQPSK format. Regeneration of 22
      Gb/s OOK signals with amplified spontaneous emission (ASE) noise and DPSK data
      signals degraded with amplitude, phase and ASE noise is experimentally validated
      demonstrating a power penalty improvement up to 1.5 dB.

PMID- 21716381
TI  - Feasibility of U-curve method to select the regularization parameter for
      fluorescence diffuse optical tomography in phantom and small animal studies.
AB  - When dealing with ill-posed problems such as fluorescence diffuse optical
      tomography (fDOT) the choice of the regularization parameter is extremely
      important for computing a reliable reconstruction. Several automatic methods for
      the selection of the regularization parameter have been introduced over the years
      and their performance depends on the particular inverse problem. Herein a U-curve
      based algorithm for the selection of regularization parameter has been applied
      for the first time to fDOT. To increase the computational efficiency for large
      systems an interval of the regularization parameter is desirable. The U-curve
      provided a suitable selection of the regularization parameter in terms of
      Picard's condition, image resolution and image noise. Results are shown both on
      phantom and mouse data.

PMID- 21716382
TI  - High contrast 40Gbit/s optical modulation in silicon.
AB  - Data interconnects are on the verge of a revolution. Electrical links are
      increasingly being pushed to their limits with the ever increasing demand for
      bandwidth. Data transmission in the optical domain is a leading candidate to
      satisfy this need. The optical modulator is key to most applications and
      increasing the data rate at which it operates is important for reducing power
      consumption, increasing channel bandwidth limitations and improving the
      efficiency of infrastructure usage. In this work silicon based devices of lengths
      3.5mm and 1mm operating at 40Gbit/s are demonstrated with extinction ratios of up
      to 10dB and 3.5dB respectively. The efficiency and optical loss of the phase
      shifter is 2.7V.cm and 4dB/mm (or 4.5dB/mm including waveguide loss)
      respectively.

PMID- 21716383
TI  - The serpentine optical waveguide: engineering the dispersion relations and the
      stopped light points.
AB  - We present a study a new type of optical slow-light structure comprising a
      serpentine shaped waveguide were the loops are coupled. The dispersion relation,
      group velocity and GVD are studied analytically using a transfer matrix method
      and numerically using finite difference time domain simulations. The structure
      exhibits zero group velocity points at the ends of the Brillouin zone, but also
      within the zone. The position of mid-zone zero group velocity point can be tuned
      by modifying the coupling coefficient between adjacent loops. Closed-form
      analytic expressions for the dispersion relations, group velocity and the mid
      zone zero v(g) points are found and presented.

PMID- 21716384
TI  - Reduced propagation loss in silicon strip and slot waveguides coated by atomic
      layer deposition.
AB  - When silicon strip and slot waveguides are coated with a 50 nm amorphous titanium
      dioxide (TiO2) film, measured losses at a wavelength of 1.55 MUm can be as low as
      (2 +/- 1)dB/cm and (7 +/- 2)dB/cm, respectively. We use atomic layer deposition
      (ALD), estimate the effect of ALD growth on the surface roughness, and discuss
      the effect on the scattering losses. Because the gap between the rails of a slot
      waveguide narrows by the TiO2 deposition, the effective slot width can be back
      end controlled. This is useful for precise adjustment if the slot is to be filled
      with, e. g., a nonlinear organic material or with a sensitizer for sensors
      applications.

PMID- 21716385
TI  - Quantitative analysis and measurements of near-field interactions in terahertz
      microscopes.
AB  - We demonstrated quantitative analysis and measurements of near-fields
      interactions in a terahertz pulse near-field microscope. We developed a self
      consistent line dipole image method for the quantitative analysis of the near
      field interaction in THz scattering-type scanning optical microscopes. The
      measurements of approach curves and relative contrasts on gold and silicon
      substrates were in excellent agreement with calculations.

PMID- 21716386
TI  - Enhanced transmission through subwavelength apertures by excitation of particle
      localized plasmons and nanojets.
AB  - We study, and illustrate with numerical calculations, transmission enhancement by
      subwavelength 2D slits due to the dominant role played by the excitation of the
      eigenmodes of plasmonic cylinders when they are placed at the aperture entrance;
      and also due to reinforced and highly localized energy in the slit as a
      consequence of the formation of a nanojet. We show that, providing the
      illumination is chosen such that an aperture transmitting eigenmode is generated,
      the phenomenon is independent of whether or not the slit alone produces
      extraordinary transmission; although in the former case this enhancement will add
      to this slit supertransmission. We address several particle sizes, and emphasize
      the universality of this phenomenon with different materials.

PMID- 21716387
TI  - Vectorial coherence holography.
AB  - Extension of coherence holography to vectorial regime is investigated. A
      technique for controlling and synthesizing optical fields with desired elements
      of coherence-polarization matrix is proposed and experimentally demonstrated. The
      technique uses two separate coherence holograms, each of which is assigned to one
      of the orthogonal polarization components of the vectorial fields.

PMID- 21716388
TI  - Drive-noise-tolerant broadband silicon electro-optic switch.
AB  - We report a broadband digital electro-optical switch, based upon a multi-stage
      Mach-Zehnder lattice design in silicon-on-insulator. A digital switching response
      is demonstrated, engineered through apodization of the coupling coefficients
      between stages. The digital switching behavior results in crosstalk lower than 
      15 dB for drive-voltage noise levels in excess of 300 mV(pp), which exceeds the
      noise tolerance of a conventional single-stage Mach-Zehnder switch by more than
      six-fold. In addition, the digital design enables a larger maximum 'on'-state
      extinction (below -26 dB) and lower 'on'-state free-carrier-induced insertion
      loss (less than 0.45 dB) than that of the single-stage switch. The noise
      tolerant, low-crosstalk switch can thus play a key role within CMOS-integrated
      reconfigurable optical networks operating under noisy on-chip conditions.

PMID- 21716389
TI  - Numerical model for tomographic image formation in transmission x-ray microscopy.
AB  - We present a numerical image-formation model for investigating the influence of
      partial coherence, sample thickness and depth-of-focus on the accuracy of
      tomographic reconstructions in transmission x-ray microscopes. The model combines
      wave propagation through the object by finite difference techniques with Fourier
      methods. We include a ray-tracing model to analyse the origin of detrimental
      stray light in zone plate-based x-ray microscopes. These models allow
      optimization of x-ray microscopy systems for quantitative tomographic imaging of
      thick objects. Results show that both the depth-of-focus and the reconstructed
      local absorption coefficient are highly dependent on the degree of coherence of
      the optical system.

PMID- 21716390
TI  - On-chip two-octave supercontinuum generation by enhancing self-steepening of
      optical pulses.
AB  - Dramatic advances in supercontinuum generation have been made recently using
      photonic crystal fibers, but it is quite challenging to obtain an octave-spanning
      supercontinuum on a chip, partially because of strong dispersion in high-index
      contrast nonlinear integrated waveguides. We show by simulation that extremely
      flat and low dispersion can be achieved in silicon nitride slot waveguides over a
      wavelength band of 500 nm. Different from most of previously reported
      supercontinua that were generated either by higher-order soliton fission in
      anomalous dispersion regime or by self-phase modulation in normal dispersion
      regime, a two-octave supercontinuum from 630 to 2650 nm (360 THz in total) can be
      generated by enhancing self-steepening in pulse propagation in nearly zero
      dispersion regime, when an optical shock as short as 3 fs is formed.

PMID- 21716391
TI  - Optical vortex converter with helical-periodically poled ferroelectric crystal.
AB  - A kind of optical vortex converter is proposed in helical-periodically poled
      ferroelectric crystal based on transverse electro-optics effect. It can be used
      to generate optical vortex from non-vortex beam and transform the topological
      charge of optical vortex. An optical vortex adder or substrator is proposed under
      the control of electric filed. This device will find its applications in high
      dimensional communication system for signal processing and optical manipulation
      in micro and mesoscopic scale.

PMID- 21716392
TI  - Fabrication of binary Fresnel lenses in PMMA by femtosecond laser surface
      ablation.
AB  - We report on the fabrication of binary Fresnel lenses by femtosecond laser
      surface ablation of poly(methyl methacrylate) (PMMA) substrates. Tight focusing
      of the laser pulses produced a minimum ablated feature size of 600 nm, enabling
      the creation of lenses with numerical apertures as high as 0.5 and focal lengths
      ranging from 500 um to 5 mm. A precise control of the ablation depth allowed the
      achievement of a 30% focusing efficiency, close to the maximum theoretical value
      for this kind of lenses.

PMID- 21716393
TI  - Optimizing low loss negative index metamaterial for visible spectrum using
      differential evolution.
AB  - A novel negative index metamaterial design methodology for the visible spectrum
      with low losses was presented in this paper. A robust differential evolution (DE)
      was employed to optimize the metamaterial design to achieve a desired set of
      values for the index of refraction. By using numerical simulation of a wedge
      shaped model and S-parameter retrieval method, we found that the DE-designed
      optimal solution can exhibit a low loss LH frequency band with simultaneously
      negative values of effective permittivity and permeability at the violet-light
      wavelength of 408 nm, and the figure of merit is 15.2, that means it may have
      practical applications because of its low loss and high transmission. Therefore,
      the design methodology presented in this paper is a very convenient and efficient
      way to pursue a novel metamaterial with desired electromagnetic characteristics
      in the visible spectrum.

PMID- 21716394
TI  - A compact orbital angular momentum spectrometer using quantum Zeno interrogation.
AB  - We present a scheme to measure the orbital angular momentum spectrum of light
      using a precisely timed optical loop and quantum non-demolition measurements. We
      also discuss the influence of imperfect optical components.

PMID- 21716395
TI  - Lifetime distribution of spontaneous emission from emitter(s) in three
      dimensional woodpile photonic crystals.
AB  - Spontaneous emission lifetime distribution in the basic unit cell or on a plane
      of the excited emitters embedded in woodpile photonics crystals with low
      refractive index contrast are investigated. It is found that the spontaneous
      emission lifetime distribution strongly depends on the position and transition
      frequency of the emitters, and has the same symmetry as that of the unit cell.
      The lifetimes of emitters near the upper gap edge are longer than that in the
      center of the pseudo-gap, which is quite a contrast to the conventional concept.
      Furthermore, it is revealed that the polarization orientation of the emitters has
      significant influence on the lifetime distribution, and may result in a high
      anisotropy factor (defined as the difference between the maximum and minimum
      values of the lifetime) up to 4.2. These results may be supplied in probing the
      lifetime distribution or orientation-dependent local density of states in future
      experiments.

PMID- 21716396
TI  - 13.1 W, high-beam-quality, narrow-linewidth continuous-wave fiber-based source at
      970 nm.
AB  - We report an efficient fiber-laser-based source of high-power, continuous-wave
      (cw), linearly-polarized radiation at 970 nm in a simple, compact, and practical
      design. Using direct single-pass second-harmonic-generation (SP-SHG) of a cw
      thulium fiber laser at 1940 nm in a 40-mm-long periodically-poled LiNbO3 (PPLN)
      crystal, we have generated 13.1 W of output power at 970 nm for a fundamental
      power of 40 W at a conversion efficiency as high as 32.7%. The generated second
      harmonic output exhibits a passive power stability better than 1.4% (1sigma
      value) over 1 hour, has a linewidth better than 0.3 nm, and a TEM(00) spatial
      beam profile with M(2)<1.6. Relevant theoretical calculations for the
      characterization of SP-SHG in the crystal have also been performed.

PMID- 21716397
TI  - Zeptosecond precision pulse shaping.
AB  - We investigate the temporal precision in the generation of ultrashort laser pulse
      pairs by pulse shaping techniques. To this end, we combine a femtosecond
      polarization pulse shaper with a polarizer and employ two linear spectral phase
      masks to mimic an ultrastable common-path interferometer. In an all-optical
      experiment we study the interference signal resulting from two temporally delayed
      pulses. Our results show a 2sigma-precision of 300 zs = 300 * 10(-21) s in pulse
      to-pulse delay. The standard deviation of the mean is 11 zs. The obtained
      precision corresponds to a variation of the arm's length in conventional delay
      stage based interferometers of 0.45 A. We apply these precisely generated pulse
      pairs to a strong-field quantum control experiment. Coherent control of ultrafast
      electron dynamics via photon locking by temporal phase discontinuities on a few
      attosecond timescale is demonstrated.

PMID- 21716398
TI  - Free-space optical delay interferometer with tunable delay and phase.
AB  - A free-space optical delay interferometer (DI) featuring a continuously tunable
      time delay, polarization insensitive operation with high extinction ratios and
      accurate phase and time delay monitoring scheme is reported. The polarization
      dependence is actively mitigated by adjusting a birefringent liquid-crystal
      device. The DI has been tested for reception of D(m)PSK signals.

PMID- 21716399
TI  - Nd:YAG single-crystal fiber as high peak power amplifier of pulses below one
      nanosecond.
AB  - We explore the potential of Nd:YAG single-crystal fibers for the amplification of
      passively Q-switched microlasers operating below 1 ns. Different regimes are
      tested in single or double pass configurations. For high gain and high power
      amplification this novel gain medium provided average powers up to 20 W at high
      repetition rate (over 40 kHz) for a pulse duration of 1 ns. As an energy
      amplifier, Nd:YAG single-crystal fiber delivered 2.7 mJ, 6 MW 450 ps pulses at 1
      kHz. The extraction efficiencies vary from 8% to 32.7% following the
      configurations.

PMID- 21716400
TI  - Evolution of photo-induced defects in Ge-doped fiber/preform: influence of the
      drawing.
AB  - We have studied the generation mechanisms of two different radiation-induced
      point defects, the Ge(1) and Ge(2) centers, in a germanosilicate fiber and in its
      original preform. The samples have been investigated before and after X-ray
      irradiation using the confocal microscopy luminescence and the electron
      paramagnetic resonance techniques. Our experimental results show the higher
      radiation sensitivity of the fiber as compared to the perform and suggest a
      relation between Ge(1) and Ge(2) generation. To explain our data we have used
      different models, finding that the destruction probability of the Ge(1) and Ge(2)
      defects is larger in fiber than in preform, whereas the generation one is
      similar. Finally we found that the higher radiation sensitivity of the fiber at
      low doses is essentially related to the presence of germanium lone pair center
      generated by the drawing.

PMID- 21716401
TI  - In-plane rotation classification for coherent X-ray imaging of single
      biomolecules.
AB  - We report a new classification scheme with computation complexity well within the
      capacity of a PC for coherent X-ray imaging of single biomolecules. In contrast
      to current methods, which are based on data from large scattering angles, we
      propose to classify the orientations of the biomolecule using data from small
      angle scattering, where the signals are relatively strong. Further we integrate
      data to form radial and azimuthal distributions of the scattering pattern to
      reduce the variance caused by the shot noise. Classification based on these two
      distributions are shown to successfully recognize not only the patterns from
      molecules of the same orientation but also those that differ by an in-plane
      rotation.

PMID- 21716402
TI  - Phase-regenerative wavelength conversion in periodically poled lithium niobate
      waveguides.
AB  - We propose and experimentally demonstrate phase-regenerative wavelength
      conversion in periodically poled lithium niobate waveguides, using either: a
      single-stage implementation based on a simultaneous combination of two cascaded
      second-order nonlinear effects in a single periodically poled lithium niobate
      waveguide, or a two-stage implementation where two separate devices are used in
      sequence to give rise to the same nonlinear effects. The phase regeneration
      properties of the proposed wavelength conversion schemes are also investigated.

PMID- 21716403
TI  - Image-based registration for synthetic aperture holography.
AB  - High pixel count apertures for digital holography may be synthesized by scanning
      smaller aperture detector arrays. Characterization and compensation for
      registration errors in the detector array position and pitch and for phase
      instability between the reference and object field is a major challenge in
      scanned systems. We use a secondary sensor to monitor phase and image-based
      registration parameter estimators to demonstrate near diffraction-limited
      resolution from a 63.4 mm aperture synthesized by scanning a 5.28 mm subaperture
      over 144 transverse positions. We demonstrate 60 MUm resolution at 2 m range.

PMID- 21716404
TI  - Enhanced two-photon excited fluorescence in three-dimensionally crosslinked
      bovine serum albumin microstructures.
AB  - In this study, the intensity of two-photon excited fluorescence (TPEF) of
      xanthene dye, Rose Bengal (RB), was significantly enhanced via bovine serum
      albumin (BSA) microstructures fabricated by the two-photon crosslinking (TPC)
      technique. The RB was utilized as the photoactivator in the TPC processing and
      the enhanced TPEF intensity correlates with the concentration of fabricated
      crosslinked BSA microstructures via the power control and pulse selection of the
      employed femtosecond laser. As a result, fabrication of three-dimensional BSA
      microstructures can be simultaneously monitored by the use of TPEF intensity. The
      crosslinked BSA microstructures synthesized may be used as an ordered biomaterial
      for fluorescence enhancement.

PMID- 21716405
TI  - Silicon ring isolators with bonded nonreciprocal magneto-optic garnets.
AB  - A ring isolator is demonstrated for the first time by directly bonding a cerium
      substituted yttrium iron garnet (Ce:YIG) onto a silicon ring resonator using
      oxygen plasma enhanced bonding. The silicon waveguide is 600 nm wide and 295 nm
      thick with 500-nm-thick Ce:YIG on the top to have reasonable nonreciprocal effect
      and low optical loss. With a radial magnetic field applied to the ring isolator,
      it exhibits 9-dB isolation at resonance in the 1550 nm wavelength regime.

PMID- 21716406
TI  - Low-loss hybrid plasmonic waveguide for compact and high-efficient photonic
      integration.
AB  - A new hybrid plasmonic waveguide is introduced and characterized in the paper. By
      coupling the photonic modes of a Si waveguide with the higher-order plasmonic
      modes of a silver nanowire, we demonstrate that the resultant hybrid modes
      possess small mode areas and long propagation distances, as well as high
      excitation efficiency (~90%) from the conventional dielectric modes. Such hybrid
      waveguides may find applications in the high-dense photonic integrations.

PMID- 21716407
TI  - Upconversion luminescence of an insulator involving a band to band multiphoton
      excitation process.
AB  - A multiphoton process to the conduction band of the insulator Er2O3 is reported,
      which occurs in vacuum under near infrared excitation. The enormous upconversion
      intensity is two orders of magnitude greater than that in air, and also the
      intensity ratio for green and red emission bands is inverted. The mechanism is
      probed by experiments of laser power dependence, cathodoluminescence,
      photoconductivity dependence and chemical dilution, and it involves cross
      relaxation energy transfer upconversion of erbium ions to reach the conduction
      band. The upconversion color is tunable by changes in pressure, laser diode
      intensity and wavelength, or dopant ion concentration.

PMID- 21716408
TI  - Under-filling trapping objectives optimizes the use of the available laser power
      in optical tweezers.
AB  - For optical tweezers, especially when used in biological studies, optimizing the
      trapping efficiency reduces photo damage or enables the generation of larger
      trapping forces. One important, yet not-well understood, tuning parameter is how
      much the laser beam needs to be expanded before coupling it into the trapping
      objective. Here, we measured the trap stiffness for 0.5-2 MUm-diameter
      microspheres for various beam expansions. We show that the highest overall
      trapping efficiency is achieved by slightly under-filling a high-numerical
      aperture objective when using microspheres with a diameter corresponding to about
      the trapping-laser wavelength in the medium. The optimal filling ratio for the
      lateral direction depended on the microsphere size, whereas for the axial
      direction it was nearly independent. Our findings are in agreement with Mie
      theory calculations and suggest that apart from the choice of the optimal
      microsphere size, slightly under-filling the objective is key for the optimal
      performance of an optical trap.

PMID- 21716409
TI  - Refractometer based on fiber Bragg grating Fabry-Perot cavity embedded with a
      narrow microchannel.
AB  - We report on inscription of microchannels of different widths in optical fiber
      using femtosecond (fs) laser inscription assisted chemical etching and the
      narrowest channel has been created with a width down to only 1.2MUm.
      Microchannels with 5MUm and 35MUm widths were fabricated together with Fabry
      Perot (FP) cavities formed by UV laser written fiber Bragg gratings (FBGs),
      creating high function and linear response refractometers. The device with a 5MUm
      microchannel has exhibited a refractive index (RI) detection range up to 1.7,
      significantly higher than all fiber grating RI sensors. In addition, the
      microchannel FBG FP structures have been theoretically simulated showing
      excellent agreement with experimental measured characteristics.

PMID- 21716410
TI  - Electronically tunable silicon photonic delay lines.
AB  - Electronically tunable optical true-time delay lines are proposed. The devices
      utilize the combination of apodised gratings and the free-carrier plasma effect
      to tune the enhanced delay of silicon waveguides at a fixed wavelength. Three
      variations of the proposed scheme are studied and compared. The compact and
      integrable devices can achieve tuning ranges as high as ~660 ps with a loss of <
      2.2 dB when operated in the reflection mode of the gratings. A delay of ~40 ps
      with a loss of < 10 dB and an estimated operation bit rate of ~20 Gb/s can be
      achieved.

PMID- 21716411
TI  - CeF3 and PrF3 as UV-visible Faraday rotators.
AB  - CeF3 and PrF3 single crystals are investigated as Faraday rotators for the UV
      visible region. Their properties are compared with those of the industrial
      standard reference terbium-gallium-garnet (TGG) single crystal. In contrast to
      TGG, CeF3 exhibits a higher transparency in the whole near UV-visible-IR, and a
      remarkable higher figure of merit which rapidly increases towards the cutoff. In
      the case of PrF3, the transparency extends to even shorter wavelengths, and
      analogously to CeF3 its figure of merit increases notably in the UV. These
      results indicate the potential of CeF3 and PrF3 as optical isolators in the UV
      visible, where at present there are no alternative candidates.

PMID- 21716412
TI  - Low-frequency transmitted intensity noise induced by stimulated Brillouin
      scattering in optical fibers.
AB  - We study theoretically and experimentally the spectral properties of low
      frequency transmitted intensity noise induced by stimulated Brillouin scattering
      in optical fibers. In fibers with a length of 25 km the Brillouin scattering
      induces transmitted intensity noise with a bandwidth on the order of tens of kHz.
      The power spectral density of the noise can be stronger than the shot noise in
      the photo-detector even when the optical power is significantly lower than the
      Brillouin threshold. The low-frequency transmitted intensity noise is caused due
      to depletion of the pump wave by the stochastic Brillouin wave. Since pump
      depletion occurs over a long distance, noise with a narrow bandwidth is generated
      in the transmitted wave. When the pump power is high enough, the spectrum of the
      induced noise contains features such as hole at low frequencies and ripples. Good
      quantitative agreement between theory and experiments is obtained. Low-frequency
      intensity noise induced by Brillouin scattering may limit the generation of ultra
      low noise signals in optoelectronic oscillators and may limit the transfer of
      ultra-low noise signals in fibers.

PMID- 21716413
TI  - 40 Gb/s silicon photonics modulator for TE and TM polarisations.
AB  - A key device in future high speed short reach interconnect technology will be the
      optical modulator. These devices, in silicon, have experienced dramatic
      improvements over the last 6 years and the modulation bandwidth has increased
      from a few tens of MHz to over 30 GHz. However, the demands of optical
      interconnects are significant. Here we describe an approach based on a self
      aligned wrap around p-n junction structure embedded in a silicon waveguide that
      can produce high-speed optical phase modulation, whilst at the same time, capable
      of a high extinction ratio. An all-silicon optical modulator using a CMOS
      compatible fabrication process with a data rate of 40 Gb/s and extinction ratio
      up to approximately 6.5 dB for TE and TM polarisations is demonstrated. This
      technology is not only compatible with conventional complementary MOS (CMOS)
      processing, but is also intended to simplify and improve the reliability of, the
      fabrication process.

PMID- 21716414
TI  - Determination of the evolution of layer thickness errors and interfacial
      imperfections in ultrathin sputtered Cr/C multilayers using high-resolution
      transmission electron microscopy.
AB  - The structures of ultrathin sputtered Cr/C multilayers were determined by high
      resolution transmission electron microscopy. The evolution of layer thickness
      errors, interdiffusion and interfacial roughness were simulated using time series
      models. The results show that with increasing of interdiffusion and roughness the
      multilayer thickness ratio changes, thereby influencing the optical performance.
      All structural parameters show good correlation with and influence adjacent
      layers. The system errors of the deposition equipment can also be evaluated by
      the models.

PMID- 21716415
TI  - Dual liquid crystal alignment configuration based on nanoparticle-doped polymer
      films.
AB  - This paper proposes an approach for producing dual liquid crystal (LC) alignment
      configuration based on nanoparticle-doped polymer films. Experimental results
      indicate that illuminating a nanoparticle-doped pre-polymer film, coated onto a
      substrate with a homogeneous alignment layer, with unpolarized UV light through a
      photomask causes the polymerization of pre-polymer, ultimately generating
      homogeneous and vertical alignment layers in unpolymerized and polymerized
      regions, respectively. The dual LC alignment configuration of the homogeneous
      (vertical) and hybrid alignments can be achieved by combining the treated
      substrate with another substrate that has a homogeneous (vertical) alignment
      layer. Additionally, the applications of the dual LC alignment layer in phase
      gratings and transflective LC displays are demonstrated.

PMID- 21716416
TI  - Dynamic generation of robust and controlled beating signals in an asymmetric
      procedure of light storage and retrieval.
AB  - We propose an efficient scheme for the robust and controlled generation of
      beating signals in a sample of stationary atoms driven into the tripod
      configuration. This scheme relies on an asymmetric procedure of light storage and
      retrieval where the two classical coupling fields have equal detunings in the
      storage stage but opposite detunings in the retrieval stage. A quantum probe
      field, incident upon such an atomic sample, is first transformed into two spin
      coherence wave-packets and then retrieved with two optical components
      characterized by different time-dependent phases. Therefore the retrieved quantum
      probe field exhibits a series of maxima and minima (beating signals) in intensity
      due to the alternative constructive and destructive interference. This
      interesting phenomenon involves in fact the coherent manipulation of two dark
      state polaritons and may be explored to achieve the fast quantum limited
      measurement.

PMID- 21716417
TI  - 42.7 Gbit/s electro-optic modulator in silicon technology.
AB  - CMOS-compatible optical modulators are key components for future silicon-based
      photonic transceivers. However, achieving low modulation voltage and high speed
      operation still remains a challenge. As a possible solution, the silicon-organic
      hybrid (SOH) platform has been proposed. In the SOH approach the optical signal
      is guided by a silicon waveguide while the electro-optic effect is provided by an
      organic cladding with a high chi(2)-nonlinearity. In these modulators the optical
      nonlinear region needs to be connected to the modulating electrical source. This
      requires electrodes, which are both optically transparent and electrically highly
      conductive. To this end we introduce a highly conductive electron accumulation
      layer which is induced by an external DC "gate" voltage. As opposed to doping,
      the electron mobility is not impaired by impurity scattering. This way we
      demonstrate for the first time data encoding with an SOH electro-optic modulator.
      Using a first-generation device at a data-rate of 42.7 Gbit/s, widely open eye
      diagrams were recorded. The measured frequency response suggests that
      significantly larger data rates are feasible.

PMID- 21716418
TI  - Solid-core photonic bandgap fibers for cladding-pumped Raman amplification.
AB  - Cladding-pumped solid-core photonic bandgap Raman fiber amplifiers are analyzed
      theoretically as possible candidates for power scaling. An example fiber design
      with a mode field diameter of 46 um and a cladding diameter of 250 um is
      calculated to exhibit 0.12 dB/km of confinement loss at the first Stokes
      wavelength and >10 dB/m at the second Stokes wavelength for a pump wavelength of
      1.567 um while maintaining low loss and large mode area in realistic coiling
      configurations. A Raman amplifier based on this fiber with 85 kW of output power,
      78% optical conversion efficiency, a maximum heat load of 130 W/m, and a length
      of 235 m is simulated.

PMID- 21716419
TI  - High-gain, wide-dynamic-range parametric interaction in Mg-doped LiNbO3 quasi
      phase-matched adhered ridge waveguide.
AB  - With recent developments and optimizations for quasi-phase-matched adhered ridge
      waveguide (QPM-ARW), outstanding performances containing efficient amplification
      were demonstrated by difference frequency generation (DFG) and optical parametric
      amplification (OPA). A maximum channel conversion efficiency of +7.6 dB (570%)
      was achieved in a telecommunication band using a 50 mm-long device, when coupling
      with 160 mW pump. Simultaneously, the input signal was amplified up to +9.5 dB
      (890%).

PMID- 21716420
TI  - Electroluminescence of ZnO nanocrystal in sputtered ZnO-SiO2 nanocomposite light
      emitting devices.
AB  - We have demonstrated the electroluminescence (EL) of Ga:ZnO/i-ZnO-SiO2
      nanocomposite/p-GaN n-i-p heterostructure light-emitting devices (LEDs). ZnO nano
      clusters with sizes distributing from 2 to 7nm were found inside the co-sputtered
      i-ZnO-SiO2 nanocomposite layer under the observation of high-resolution
      transparent electron microscope. A clear UV EL at 376 nm from i-ZnO-SiO2
      nanocomposite in these p-i-n heterostructure LEDs was observed under the forward
      current of 9 mA. The EL emission peak at 376 and 427nm of the Ga:ZnO/i-ZnO-SiO2
      nanocomposite/p-GaN n-i-p heterostructure LEDs were attributed to the radiative
      recombination from the ZnO clusters and the Mg acceptor levels in the p-GaN
      layer, respectively.

PMID- 21716421
TI  - Imaging vibrating vocal folds with a high speed 1050 nm swept source OCT and ODT.
AB  - Vocal fold vibration is vital in voice production and the correct pitch of
      speech. We have developed a high speed functional optical coherence tomography
      (OCT) system with a center wavelength of 1050 nm and an imaging speed of 100,000
      A-lines per second. We imaged the vibration of an ex-vivo swine vocal fold. At an
      imaging speed of 100 frames per second, we demonstrated high quality vocal fold
      images during vibration. Functional information, such as vibration frequency and
      vibration amplitude, was obtained by analyzing the tissue surface during
      vibration. The axial direction velocity distribution in the cross-sectional
      images of the vibrating vocal folds was obtained with the Doppler OCT. The
      quantitative transverse direction velocity distribution in the cross-sectional
      images was obtained with the Doppler variance images.

PMID- 21716422
TI  - Electrically tunable liquid crystal waveguide attenuators.
AB  - The attenuator for the wavelength at 1550 nm is fabricated by using the capillary
      effect to infiltrate liquid crystal (LC) E7 into hollow waveguides (HWGs) on
      silicon substrate with SiO2 cladding layer. The length of the waveguide is 0.4
      cm. The device can be operated with relatively low driving voltage below 5 V(pp)
      with the distance between two electrodes to be 9 MUm. The light attenuation of
      the device can be over 30 dB. The performance of the device is independent of the
      polarization states of the input light.

PMID- 21716423
TI  - Spherical silicon micromirrors bent by anodic bonding.
AB  - We propose here a novel and stable method for fabricating spherical micromirror
      by bonding a flat freestanding single-crystal-silicon (SCS) membrane with a
      fulcrum on a glass substrate. Smooth convex spherical surface is achieved inside
      the fulcrum by the bending moment generated in the circumference of the SCS
      membrane. The surface profiles fit well with parabolic curves within 36nm RMS
      error indicating a good optical performance. By modifying the diameter of the
      fulcrum, we also demonstrate that it is possible to fabricate micromirrors with a
      wide range of focal length (0.4mm-1.6mm). The fabricated micromirrors are also
      used as the mold for replication of micro polymeric lenses. The surface profiles
      of the micromirrors are transferred to the polymeric replica with a high
      accuracy.

PMID- 21716424
TI  - Suspended-core fiber Sagnac combined dual-random mirror Raman fiber laser.
AB  - In the present work, a multiwavelength fiber laser based in the combination of a
      double-random mirror and a suspended-core Sagnac interferometer is presented. The
      double-random mirror acts by itself as a random laser, presenting a 30dB SNR, as
      result of multiple Rayleigh scattering events produced in the dispersion
      compensating fibers by the Raman amplification. The suspended-core fiber Sagnac
      interferometer provides the multi peak channeled spectrum, which can be tuned by
      changing the length of the fiber. The result of this combination is a stable
      multiwavelength peak laser with a minimum of ~25dB SNR, which is highly sensitive
      to polarization induced variations.

PMID- 21716425
TI  - Statistical studies of photonic heterostructure nanocavities with an average Q
      factor of three million.
AB  - We have measured the quality (Q) factors and resonant wavelengths for 80 photonic
      crystal nanocavities with the same heterostructure. In this statistical
      evaluation, the Q factors varied according to a normal distribution centered at 3
      million and ranging between 2.3 million and 3.9 million. The resonant wavelengths
      also fluctuated but with a standard deviation of only 0.33 nm. Such a high
      average Q factor and highly controlled resonant wavelength will be important for
      the development of advanced applications of photonic crystal nanocavities.
      Comparing the experimental values with calculated values suggests that factors
      other than structural variations of air holes, which decrease the Q factor, are
      indeed present in the fabricated nanocavities.

PMID- 21716426
TI  - Alternate formulation of enhanced backscattering as phase conjugation and
      diffraction: derivation and experimental observation.
AB  - Enhanced backscattering (EBS), also known as weak localization of light, is
      derived using the Huygens-Fresnel principle and backscattering is generally shown
      to be the sum of an incoherent baseline and a phase conjugated portion of the
      incident wave that forms EBS. The phase conjugated portion is truncated by an
      effective aperture described by the probability function P(s) of coherent path
      pair separations. P(s) is determined by the scattering properties of the medium
      and so characterization of EBS can be used for metrology of scattering materials.
      A three dimensional intensity peak is predicted in free space at a point
      conjugate to the source and is experimentally observed.

PMID- 21716427
TI  - Iterative reconstruction of projection images from a microlens-based optical
      detector.
AB  - A microlens-based optical detector was developed to perform small animal optical
      imaging. In this paper we present an iterative reconstruction algorithm yielding
      improved image quality and spatial resolution as compared to conventional inverse
      mapping. The reconstruction method utilizes the compressive sensing concept to
      cope with the undersampling nature of the problem. Each iteration in the
      algorithm contains two separate steps to ensure both the convergence of the least
      square solution and the minimization of the l(1)-norm of the sparsifying
      transform. The results estimated from measurements, employing a Derenzo-like
      pattern and a Siemens star phantom, illustrate significant improvements in
      contrast and spatial resolution in comparison to results calculated by inverse
      mapping.

PMID- 21716428
TI  - Influence of quantum coherence on propagation of a pulsed light in a triple
      quantum well.
AB  - In a triple semiconductor quantum well structure coupled by two external fields,
      we investigate the influence of atomic coherence induced by external fields and
      decay interference on the absorption and dispersion of a weak pulsed light, and
      slow light can be achieved in this system. Quantum well structure behaves as
      "artificial atom" and its advantage of easy integration makes it has some
      practical applications.

PMID- 21716429
TI  - Simulation of an erbium-doped chalcogenide micro-disk mid-infrared laser source.
AB  - The feasibility of mid-infrared (MIR) lasing in erbium-doped gallium lanthanum
      sulfide (GLS) micro-disks was examined. Lasing condition at 4.5 um signal using
      800 nm pump source was simulated using rate equations, mode propagation and
      transfer matrix formulation. Cavity quality (Q) factors of 1.48 * 10(4) and 1.53
      * 10(6) were assumed at the pump and signal wavelengths, respectively, based on
      state-of-the-art chalcogenide micro-disk resonator parameters. With an 80 um disk
      diameter and an active erbium concentration of 2.8 * 10(20) cm(-3), lasing was
      shown to be possible with a maximum slope efficiency of 1.26 * 10(-4) and
      associated pump threshold of 0.5 mW.

PMID- 21716430
TI  - Higher-order vector beams produced by photonic-crystal lasers.
AB  - We have successfully generated vector beams with higher-order polarization states
      using photonic-crystal lasers. We have analyzed and designed lattice structures
      that provide cavity modes with different symmetries. Fabricated devices based on
      these lattice structures produced doughnut-shaped vector beams, with symmetries
      corresponding to the cavity modes. Our study enables the systematic analysis of
      vector beams, which we expect will lead to applications such as high-resolution
      microscopy, laser processing, and optical trapping.

PMID- 21716431
TI  - Defect-mediated resonance shift of silicon-on-insulator racetrack resonators.
AB  - We present a study on the effects of inert ion implantation of Silicon-On
      Insulator (SOI) racetrack resonators. Selective ion implantation was used to
      create deep-level defects within a portion of the resonator. The resonant
      wavelength and round-trip loss were deduced for a range of sequential post
      implantation annealing temperatures from 100 to 300  degrees C. As the devices
      were annealed there was a concomitant change in the resonance wavelength,
      consistent with an increase in refractive index following implantation and
      recovery toward the pre-implanted value. A total shift in resonance wavelength of
      ~2.9 nm was achieved, equivalent to a 0.02 increase in refractive index. The
      excess loss upon implantation increased to 301 dB/cm and was reduced to 35 dB/cm
      following thermal annealing. In addition to providing valuable data for those
      incorporating defects within resonant structures, we suggest that these results
      present a method for permanent tuning (or trimming) of ring resonator
      characteristics.

PMID- 21716432
TI  - Higher-capacity communication links based on two-mode phase-sensitive amplifiers.
AB  - Optical communication links are usually made with erbium-doped fiber amplifiers,
      which amplify the signal waves in a phase-insensitive (PI) manner. They can also
      be made with parametric fiber amplifiers, in which the signal waves interact with
      idler waves. If information is transmitted using only the signals, parametric
      amplifiers are PI and their noise figures are comparable to those of erbium
      amplifiers. However, transmitting correlated information in the signals and
      idlers, or copying the signals prior to transmission, allows parametric
      amplifiers to be phase-sensitive (PS), which lowers their noise figures. The
      information capacities of two-mode PS links exceed those of the corresponding PI
      links by 2 b/s-Hz.

PMID- 21716433
TI  - Femtosecond laser fabrication of birefringent directional couplers as
      polarization beam splitters in fused silica.
AB  - Integrated polarization beam splitters based on birefringent directional couplers
      are demonstrated. The devices are fabricated in bulk fused silica glass by
      femtosecond laser writing (300 fs, 150 nJ at 500 kHz, 522 nm). The birefringence
      was measured from the spectral splitting of the Bragg grating resonances
      associated with the vertically and horizontally polarized modes. Polarization
      splitting directional couplers were designed and demonstrated with 0.5 dB/cm
      propagation losses and -19 dB and -24 dB extinction ratios for the polarization
      splitting.

PMID- 21716434
TI  - Coherence generation and population transfer by stimulated Raman adiabatic
      passage and pi pulse in a four-level ladder system.
AB  - We propose a new scheme for achieving the complete population transfer and the
      optimal coherence generation between the ground state and the Rydberg state in a
      four-level ladder system by combining the STIRAP or fractional STIRAP technique
      and the pi pulse technique. We consider, in particular, two different situations
      where spontaneous emission from the two highest states are neglected or not. Our
      numerical calculations show that the time width and the delay time of the pi
      pulse are two critical parameters for attaining the maximal population transfer
      and coherence generation in this scheme.

PMID- 21716435
TI  - Time-division color electroholography using one-chip RGB LED and synchronizing
      controller.
AB  - We propose time-division based color electroholography with a one-chip RGB Light
      Emitting Diode (LED) and a low-priced synchronizing controller. In
      electroholography, although color reconstruction methods via time-division have
      already been proposed, the methods require an LCD with a high refresh rate and
      output signals from the LCD for synchronizing the RGB reference lights such as
      laser sources, which consequently increase the development cost. Instead of using
      such an LCD, the proposed method is capable of using a general LCD panel with a
      normal refresh rate of 60 Hz. In addition, the LCD panel used in the proposed
      method does not require the output signals from the LCD. Instead, we generated
      synchronized signals using an external controller developed by a low-priced one
      chip microprocessor, and, use a one-chip RGB LED instead of lasers as the RGB
      reference lights. The one-chip LED allows us to decrease the development cost and
      to facilitate optical-axis alignment. Using this method, we observed a multi
      color 3D reconstructed movie at a frame rate of 20 Hz.

PMID- 21716436
TI  - Near field phase mapping exploiting intrinsic oscillations of aperture NSOM
      probe.
AB  - An innovative, simple, compact and low cost approach for phase mapping based on
      the intrinsic modulation of an aperture Near Field Scanning Optical Microscope
      probe is analyzed and experimentally demonstrated. Several nanoscale silicon
      waveguides are phase-mapped using this approach, and the different modes of
      propagation are obtained via Fourier analysis. The obtained measured results are
      in good agreement with the effective indexes of the modes calculated by
      electromagnetic simulations. Owing to its simplicity and effectiveness, the
      demonstrated system is a potential candidate for integration with current near
      field systems for the characterization of nanophotonic components and devices.

PMID- 21716437
TI  - Tuning of superconducting niobium nitride terahertz metamaterials.
AB  - Superconducting planar terahertz (THz) metamaterials (MMs), with unit cells of
      different sizes, are fabricated on 200 nm-thick niobium nitride (NbN) films
      deposited on MgO substrates. They are characterized using THz time domain
      spectroscopy over a temperature range from 8.1 K to 300 K, crossing the critical
      temperature of NbN films. As the gap frequency (f(g) = 2Delta0/h, where Delta0 is
      the energy gap at 0 K and h is the Plank constant) of NbN is 1.18 THz, the
      experimentally observed THz spectra span a frequency range from below f(g) to
      above it. We have found that, as the resonance frequency approaches f(g), the
      relative tuning range of MMs is quite wide (30%). We attribute this observation
      to the large change of kinetic inductance of superconducting film.

PMID- 21716438
TI  - High-resolution synthetic-aperture digital holography with digital phase and
      pupil correction.
AB  - A 218 mega-pixel synthetic aperture was collected by raster scanning a CCD
      detector in a digital holography imaging experiment. Frames were mosaicked
      together using a two-step cross-correlation registration. Phase correction using
      sharpness metrics were utilized to achieve diffraction-limited resolution.

PMID- 21716439
TI  - Low threshold power density for the generation of frequency up-converted pulses
      in bismuth glass by two crossing chirped femtosecond pulses.
AB  - We investigated the generation of frequency up-converted femtosecond laser pulses
      by nondegenerate cascaded four-wave mixing (CFWM) in a bismuth-oxide glass (BI
      glass). Broad-bandwidth light pulses with different propagation directions were
      simultaneously obtained by using two small-angle crossing femtosecond laser
      pulses in BI glass. Experimental results show that the threshold power density
      for the generation of broad-bandwidth femtosecond pulses in BI glass is one order
      of magnitude lower than that in fused silica.

PMID- 21716440
TI  - Tunable negative-tap photonic microwave filter based on a cladding-mode coupler
      and an optically injected laser of large detuning.
AB  - A tunable negative-tap photonic microwave filter using a cladding-mode coupler
      together with optical injection locking of large wavelength detuning is
      demonstrated. Continuous and precise tunability of the filter is realized by
      physically sliding a pair of bare fibers inside the cladding-mode coupler. Signal
      inversion for the negative tap is achieved by optical injection locking of a
      single-mode semiconductor laser. To couple light into and out of the cladding
      mode coupler, a pair of matching long-period fiber gratings is employed. The
      large bandwidth of the gratings requires injection locking of an exceptionally
      large wavelength detuning that has never been demonstrated before.
      Experimentally, injection locking with wavelength detuning as large as 27 nm was
      achieved, which corresponded to locking the 36-th side mode. Microwave filtering
      with a free-spectral range tunable from 88.6 MHz to 1.57 GHz and a notch depth
      larger than 35 dB was obtained.

PMID- 21716441
TI  - Increasing the storage density of a page-based holographic data storage system by
      image upscaling using the PSF of the Nyquist aperture.
AB  - We introduce an image upscaling method that reduces bit errors caused by Nyquist
      apertures. Nyquist apertures used for higher storage densities generate optical
      aberrations and degrade the quality of the image that is recorded on the medium.
      Here, to correct the bit errors caused by the Nyquist aperture, an image
      upscaling method is used to restore the degraded image in the enhanced spatial
      frequency domain using its point spread function (PSF) as a restoration filter.
      The proposed method reduces the bit error rate (BER) significantly and hence
      allows higher storage densities.

PMID- 21716442
TI  - Single-distance phase retrieval at large phase shifts.
AB  - For coherent X-ray imaging of pure phase objects we study the reliability of
      linear relations in phase-retrieval algorithms based on a single intensity map
      after free-space propagation. For large phase changes and/or large propagation
      distances we propose two venues of working beyond linearity: Projection onto an
      effective, linear and local model in Fourier space and expansion of intensity
      contrast in powers of object-detector distance. We apply both algorithms
      successfully to simulated data.

PMID- 21716443
TI  - Generation of 42-fs and 10-nJ pulses from a fiber laser with self-similar
      evolution in the gain segment.
AB  - A double-clad Yb-doped all-normal-dispersion fiber laser with a narrow intra
      cavity spectral filter is demonstrated to produce 22 nJ pulses at 42.5 MHz
      repetition rate. These pulses are characterized and compressed via mulitphoton
      intrapulse interference phase scan to as short as 42 fs and 10 nJ/pulse. Adaptive
      compression underlies the achievement of 250-kW peak power, which enables
      efficient second and third harmonic generation with spectra spanning 30 nm and 20
      nm, respectively.

PMID- 21716444
TI  - Non-hexagonal Large-Pitch Fibers for enhanced mode discrimination.
AB  - Photonic-Crystal Fibers (PCF) are among the most promising concepts to achieve
      large mode field areas suitable for the reduction of nonlinearities in fibers.
      Differential mode propagation loss is the cornerstone of effective single-mode
      behavior in passive and core-pumped active PCFs. In this work, we explore non
      hexagonal PCF designs with increased mode discrimination in comparison to the
      classical hexagonal PCF designs. It is shown that a pentagonal design can
      increase the mode discrimination and, simultaneously, also improve the beam
      quality of Large-Pitch Fibers with mode field diameters well beyond 100 um.

PMID- 21716445
TI  - Temporal coherence and spectral linewidth of an injection-seeded transient
      collisional soft x-ray laser.
AB  - The temporal coherence of an injection-seeded transient 18.9 nm molybdenum soft x
      ray laser was measured using a wavefront division interferometer and compared to
      model simulations. The seeded laser is found to have a coherence time similar to
      that of the unseeded amplifier, ~1 ps, but a significantly larger degree of
      temporal coherence. The measured coherence time for the unseeded amplifier is
      only a small fraction of the pulsewidth, while in the case of the seeded laser it
      approaches full temporal coherence. The measurements confirm that the bandwidth
      of the solid target amplifiers is significantly wider than that of soft x-ray
      lasers that use gaseous targets, an advantage for the development of sub
      picosecond soft x-ray lasers.

PMID- 21716446
TI  - Optical response of supported gold nanodisks.
AB  - It is shown that the ellipsometric spectra of short range ordered planar arrays
      of gold nanodisks supported on glass substrates can be described by modeling the
      nanostructured arrays as uniaxial homogeneous layers with dielectric functions of
      the Lorentz type. However, appreciable deviations from experimental data are
      observed in calculated spectra of irradiance measurements. A qualitative and
      quantitative description of all measured spectra is obtained with a uniaxial
      effective medium dielectric function in which the nanodisks are modeled as oblate
      spheroids. Dynamic depolarization factors in the long-wavelength approximation
      and interaction with the substrate are considered. Similar results are obtained
      calculating the optical spectra using the island-film theory. Nevertheless, a
      small in-plane anisotropy and quadrupolar coupling effects reveal a very complex
      optical response of the nanostructured arrays.

PMID- 21716447
TI  - Low-loss VIS/IR-XUV beam splitter for high-power applications.
AB  - We present a low-loss VIS/IR-XUV beam splitter, suitable for high-power
      operation. The spatial separation of the VIS/IR and XUV components of a beam is
      achieved by the wedged top layer of a dielectric multilayer structure, onto which
      the beam is impinging under Brewster's angle (for VIS/IR). With a fused silica
      wedge with an angle of 0.5 degrees  we achieve a separation angle of 2.2 degrees 
      and an IR reflectivity of 0.9995. Typical XUV reflectivities amount to 0.1-0.2.
      The novel element is mechanically robust, exhibiting two major advantages over
      free-standing Brewster plates: (i) a significant improvement of heat conduction
      and (ii) easier handling, in particular for high-optical-quality fabrication. The
      beam splitter could be used as an output coupler for intracavity-generated XUV
      radiation, promising a boost of the power regime of current MHz-HHG experiments.
      It is also suited for single-pass experiments and as a beam combiner for pump
      probe experiments.

PMID- 21716448
TI  - Dual-negative refraction in photonic crystals with hexagonal lattices.
AB  - We present a dual-negative refraction effect based on the overlapping bands in a
      two-dimensional triangular photonic crystal formed by holographic lithography.
      Under certain conditions, one incident plane wave launched into this photonic
      crystal can be dispersed into two negative refracted waves at the same frequency
      and the same perpendicular polarization state with different phase velocities and
      group velocities. We find that this dual-negative refraction behavior can be
      easily manipulated by adjusting the incident angle, the frequency of incident
      wave and the filling ratio of the PhC. This special effect can be applied to
      realize wave-front division and optical interference in optical holography. Based
      on this effect, a double focusing imaging phenomenon has been achieved by the PhC
      slab. These unique features may show great impacts on both fundamental physics
      and optical device applications.

PMID- 21716449
TI  - GPU based real-time quadrature transform method for 3-D surface measurement and
      visualization.
AB  - In this article, we propose a massively parallel, real-time algorithm for the
      estimation of the dynamic phase map of a vibrating object. The algorithm
      implements a Fourier-based quadrature transform and temporal phase unwrapping
      technique. CUDA, a graphic processing unit programming architecture was used to
      implement the algorithm. It was tested on a fringe pattern sequence using three
      devices with different capabilities, achieving a processing rate greater than
      1600 frames per second (fps).

PMID- 21716450
TI  - Design and analysis of single mode Fabry-Perot lasers with high speed modulation
      capability.
AB  - The single mode Fabry-Perot (FP) semiconductor lasers are investigated
      systematically by a rigorous time-domain theoretical model based on the transfer
      matrix method. Static and high-speed dynamic performances under direct modulation
      and strong external optical feedbacks are simulated for both symmetric and
      asymmetric longitudinal structures of the lasers. Comparisons with the DFB and
      conventional FP lasers are made to confirm its effectiveness in achieving single
      mode lasing with high spectrum purity under modulation and feedback conditions.
      Structural optimization is also carried out with respect to the key design
      parameters.

PMID- 21716451
TI  - Extended focus high-speed swept source OCT with self-reconstructive illumination.
AB  - We present a Bessel beam illumination FDOCT setup using a FDML Swept Source at
      1300 nm with up to 440 kHz A-scan rate, and discuss its advantages for structural
      and functional imaging of highly scattering samples. An extended focus is
      achieved due to the Bessel beam that preserves its lateral extend over a large
      depth range. Furthermore, Bessel beams exhibit a self-reconstruction property
      that allows imaging even behind obstacles such as hairs on skin. Decoupling the
      illumination from the gaussian detection increases the global sensitivity and
      enables dark field imaging. Dark field imaging is useful to avoid strong reflexes
      from the sample surface that adversely affect the sensitivity due to the limited
      dynamic range of high speed 8 bit acquisition cards. In addition the possibility
      of contrasting capillaries with high sensitivity is shown, using inter-B-scan
      speckle variance analysis. We demonstrate intrinsic advantages of the extended
      focus configuration, in particular the reduction of the phase decorrelation
      effect below vessels leading to improved axial vessel definition.

PMID- 21716452
TI  - Frequency-doubled DBR-tapered diode laser for direct pumping of Ti:sapphire
      lasers generating sub-20 fs pulses.
AB  - For the first time a single-pass frequency doubled DBR-tapered diode laser
      suitable for pumping Ti:sapphire lasers generating ultrashort pulses is
      demonstrated. The maximum output powers achieved when pumping the Ti:sapphire
      laser are 110 mW (CW) and 82 mW (mode-locked) respectively at 1.2 W of pump
      power. This corresponds to a reduction in optical conversion efficiencies to 75%
      of the values achieved with a commercial diode pumped solid-state laser. However,
      the superior electro-optical efficiency of the diode laser improves the overall
      efficiency of the Ti:sapphire laser by a factor > 2. The optical spectrum emitted
      by the Ti:sapphire laser when pumped with our diode laser shows a spectral width
      of 112 nm (FWHM). Based on autocorrelation measurements, pulse widths of less
      than 20 fs can therefore be expected.

PMID- 21716453
TI  - Single rolled-up InGaAs/GaAs quantum dot microtubes integrated with silicon-on
      insulator waveguides.
AB  - We report on single rolled-up microtubes integrated with silicon-on-insulator
      waveguides. Microtubes with diameters of ~7 MUm, wall thicknesses of ~250 nm, and
      lengths greater than 100 MUm are fabricated by selectively releasing a coherently
      strained InGaAs/GaAs quantum dot layer from the handling GaAs substrate. The
      microtubes are then transferred from their host substrate to silicon-on-insulator
      waveguides by an optical fiber abrupt taper. The Q-factor of the waveguide
      coupled microtube is measured to be 1.5*10(5), the highest recorded for a
      semiconductor microtube cavity to date. The insertion loss and extinction ratio
      of the microtube are 1 dB and 34 dB respectively. By pumping the microtube with a
      635 nm laser, the resonance wavelength is shifted by 0.7 nm. The integration of
      InGaAs/GaAs microtubes with silicon-on-insulator waveguides provides a simple,
      low loss, high extinction passive filter solution in the C+L band communication
      regime.

PMID- 21716454
TI  - Simultaneous wavelength conversion of ASK and DPSK signals based on four-wave
      mixing in dispersion engineered silicon waveguides.
AB  - We experimentally demonstrate four-wave-mixing (FWM)-based continuous wavelength
      conversion of optical differential-phase-shift-keyed (DPSK) signals with large
      wavelength conversion ranges as well as simultaneous wavelength conversion of
      dual-wavelength channels with mixed modulation formats in 1.1-cm-long dispersion
      engineered silicon waveguides. We first validate up to 100-nm wavelength
      conversion range for 10-Gb/s DPSK signals, showcasing the capability to perform
      phase-preserving operations at high bit rates in chip-scale devices over wide
      conversion ranges. We further validate the wavelength conversion of dual
      wavelength channels modulated with 10-Gb/s packetized phase-shift-keyed (PSK) and
      amplitude-shift-keyed (ASK) signals; demonstrate simultaneous operation on
      multiple channels with mixed formats in chip-scale devices. For both
      configurations, we measure the spectral and temporal responses and evaluate the
      performances using bit-error-rate (BER) measurements.

PMID- 21716455
TI  - Pressure-assisted melt-filling and optical characterization of Au nano-wires in
      microstructured fibers.
AB  - We report a novel splicing-based pressure-assisted melt-filling technique for
      creating metallic nanowires in hollow channels in microstructured silica fibers.
      Wires with diameters as small as 120 nm (typical aspect ration 50:1) could be
      realized at a filling pressure of 300 bar. As an example we investigate a
      conventional single-mode step-index fiber with a parallel gold nanowire (wire
      diameter 510 nm) running next to the core. Optical transmission spectra show dips
      at wavelengths where guided surface plasmon modes on the nanowire phase match to
      the glass core mode. By monitoring the side-scattered light at narrow breaks in
      the nanowire, the loss could be estimated. Values as low as 0.7 dB/mm were
      measured at resonance, corresponding to those of an ultra-long-range eigenmode of
      the glass-core/nanowire system. By thermal treatment the hollow channel could be
      collapsed controllably, permitting creation of a conical gold nanowire, the
      optical properties of which could be monitored by side-scattering. The
      reproducibility of the technique and the high optical quality of the wires
      suggest applications in fields such as nonlinear plasmonics, near-field scanning
      optical microscope tips, cylindrical polarizers, optical sensing and
      telecommunications.

PMID- 21716456
TI  - Detection of malarial byproduct hemozoin utilizing its unique scattering
      properties.
AB  - The scattering characteristics of the malaria byproduct hemozoin, including its
      scattering distribution and depolarization, are modeled using Discrete Dipole
      Approximation (DDA) and compared to those of healthy red blood cells. Scattering
      (or dark-field) spectroscopy and imaging are used to identify hemozoin in fresh
      rodent blood samples. A new detection method is proposed and demonstrated using
      dark-field in conjunction with cross-polarization imaging and spectroscopy. SNRs
      greater than 50:1 are achieved for hemozoin in fresh blood without the addition
      of stains or reagents. The potential of such a detection system is discussed.

PMID- 21716457
TI  - Polarization insensitive 25-Gbaud direct D(Q)PSK receiver based on polymer planar
      lightwave hybrid integration platform.
AB  - We report a direct DPSK receiver based on polymer planar lightwave circuit
      technology, which incorporates a 2x25 GHz photodiode (PD) array hybridly
      integrated via 45 degrees  mirrors. In this direct DPSK receiver, a half-wave
      plate and heating electrodes are implemented to eliminate the polarization
      dependent frequency-shift (PDFS) of the delay-line interferometer (DLI). By
      applying a proper heating current, a residual PDFS of practically zero at 1550 nm
      and within +/-125 MHz was achieved over the full C-band. Integrated with the PD
      array, the peak responsivity is ~0.14 A/W for orthogonal polarizations over the C
      band. To characterize this direct receiver, we introduce an adapted common-mode
      rejection ratio (CMRR), which takes into account the unequal responsivities of
      the PDs, the uneven split of the input power by the DLI, the phase error and the
      extinction ratio of the DLI. The measured CMRR under DC condition is below -20 dB
      over the C-band.

PMID- 21716458
TI  - Localized surface-plasmon resonances on single and coupled nanoparticles through
      surface integral equations for flexible surfaces.
AB  - We present an advanced numerical formulation to calculate the optical properties
      of 3D nanoparticles (single or coupled) of arbitrary shape and lack of symmetry.
      The method is based on the (formally exact) surface integral equation
      formulation, implemented for parametric surfaces describing particles with
      arbitrary shape through a unified treatment (Gielis' formula). Extinction,
      scattering, and absorption spectra of a variety of metal nanoparticles are shown,
      thus determining rigorously the localised surface-plasmon resonances of
      nanocubes, nanostars, and nanodimers. Far-field and near-field patterns for such
      resonances are also calculated, revealing their nature. The flexibility and
      reliability of the formulation makes it specially suitable for complex scattering
      problems in Nano-Optics & Plasmonics.

PMID- 21716459
TI  - Optical vortex pumped mid-infrared optical parametric oscillator.
AB  - The first demonstration of a mid-infrared optical parametric oscillator pumped by
      1-MUm optical vortex pulses is presented. A 0.5-mJ 2-MUm fractional vortex pulse
      having half-integer topological charge is generated. Using this system, 0.24-mJ
      vortex pulses with a topological charge of 1 can be created. The topological
      charges of the mid-infrared vortex pulses are observed by an interferometric
      technique in combination with second-harmonic frequency conversion.

PMID- 21716460
TI  - Coupled-resonator-induced-transparency concept for wavelength routing
      applications.
AB  - The presence of coupled resonators induced transparency (CRIT) effects in side
      coupled integrated spaced sequence of resonators (SCISSOR) of different radii has
      been studied. By controlling the rings radii and their center to center distance,
      it is possible to form transmission channels within the SCISSOR stop-band. Two
      different methods to exploit the CRIT effect in add/drop filters are proposed.
      Their performances, e. g. linewidth, crosstalk and losses, are examined also for
      random variations in the structural parameters. Finally, few examples of high
      performances mux/demux structures and 2 * 2 routers based on these modified
      SCISSOR are presented. CRIT based SCISSOR optical devices are particularly
      promising for ultra-dense wavelength division multiplexing applications.

PMID- 21716461
TI  - Hot electron dominated rapid transverse ionization growth in liquid water.
AB  - Pump/probe optical-transmission measurements are used to monitor in space and
      time the ionization of a liquid column of water following impact of an 800-nm, 45
      fs pump pulse. The pump pulse strikes the 53-MUm-diameter column normal to its
      axis with intensities up to 2 * 10(15) W/cm2. After the initial photoinization
      and for probe delay times < 500 fs, the neutral water surrounding the beam is
      rapidly ionized in the transverse direction, presumably by hot electrons with
      initial velocities of 0.55 times the speed of light (relativistic kinetic energy
      of ~100 keV). Such velocities are unusual for condensed-matter excitation at the
      stated laser intensities.

PMID- 21716462
TI  - Performance comparison of 0/pi- and +/- pi/2-phase-shifted superstructured Fiber
      Bragg grating en/decoder.
AB  - We compare the performances of the 0/pi-phase-shifted SSFBG (0/pi-SSFBG) and the
      +/- pi/2-phase-shifted SSFBG (+/- pi/2-SSFBG) en/decoders in the three aspects:
      the security, coding and system performances. In terms of the security
      performance, we evaluate the security performance by the investigation on the
      encoded waveform of both encoders. We also propose and demonstrate the code
      extraction technique for the +/- pi/2-SSFBG encoder when input pulse has large
      pulse width. Then, we analyze the coding performance of these two kinds of
      en/decoders by the calculation of autocorrelation and cross-correlation with sets
      of 31-chip, 63-chip and 127-chip Gold codes. Furthermore, we propose and
      demonstrate the hybrid use of both en/decoders. To demonstrate the performance of
      both en/decoders and the hybrid use in the different systems, we employ four 31
      chip 640 Gchip/s 0/pi-SSFBG and +/- pi/2-SSFBG en/decoders in the 4-user 10
      Gbps/user on-off keying and differential phase-shift keying OCDMA systems.

PMID- 21716463
TI  - Signal detectability in diffusive media using phased arrays in conjunction with
      detector arrays.
AB  - We investigate Hotelling observer performance (i.e., signal detectability) of a
      phased array system for tasks of detecting small inhomogeneities and
      distinguishing adjacent abnormalities in uniform diffusive media. Unlike
      conventional phased array systems where a single detector is located on the
      interface between two sources, we consider a detector array, such as a CCD, on a
      phantom exit surface for calculating the Hotelling observer detectability. The
      signal detectability for adjacent small abnormalities (2 mm displacement) for the
      CCD-based phased array is related to the resolution of reconstructed images.
      Simulations show that acquiring high-dimensional data from a detector array in a
      phased array system dramatically improves the detectability for both tasks when
      compared to conventional single detector measurements, especially at low
      modulation frequencies. It is also observed in all studied cases that there
      exists the modulation frequency optimizing CCD-based phased array systems, where
      detectability for both tasks is consistently high. These results imply that the
      CCD-based phased array has the potential to achieve high resolution and signal
      detectability in tomographic diffusive imaging while operating at a very low
      modulation frequency. The effect of other configuration parameters, such as a
      detector pixel size, on the observer performance is also discussed.

PMID- 21716464
TI  - Pulse-preserving broadband visible supercontinuum generation in all-normal
      dispersion tapered suspended-core optical fibers.
AB  - Recently, coherent pulse-preserving and octave-spanning supercontinuum (SC)
      generation was theoretically predicted and experimentally shown in photonic
      crystal fibers (PCFs) with all-normal dispersion behavior. Since this behavior is
      due only to the all-normal dispersion profile and not to the photonic crystal
      cladding, other all-normal optical waveguides exhibit these properties as well.
      We extend this concept to suspended-core fibers and optical nanofibers and show
      experimental demonstrations of this way of SC generation. We show that optical
      suspended-core fibers and optical nanofibers of appropriate dimensions exhibit
      all-normal dispersion and address octave-spanning single pulse SC generation in
      the visible (VIS) and ultra violet (UV) wavelength range. In addition, we discuss
      the feasibility of fiber taper transitions for suitable input coupling schemes in
      sub-micron diameter fibers and show the importance of short adiabatic transition
      profiles for utilizing high-energy pulses to obtain maximum spectral broadening.
      They are essential for coherent broadband UV SC generation in optical nanofibers.

PMID- 21716465
TI  - Wavelet denoising experiments in dynamic light scattering.
AB  - Dynamic light scattering (DLS) is widely used for particle size measurement.
      Recovering accurate particle sizes from noisy DLS measurements (short duration
      and/or low count rate) is problematic. We demonstrate that denoising of the light
      scattering signal using wavelet packet filtering is beneficial and leads to more
      accurate particle sizes being recovered.

PMID- 21716466
TI  - Investigation of range profiles from buried 3-D object based on the EM
      simulation.
AB  - The 1-D range profiles are suitable features for target identification and target
      discrimination because they provide discriminative information on the geometry of
      the target. To resolve features of the buried target, the contribution from
      individual scattering centers of the buried target in the range profiles need to
      be identified. Thus, the study of complex scattering mechanisms from which the
      range profiles are produced is of great importance. In order to clearly establish
      the relationship between the range profile characteristics and the complicated
      electromagnetic (EM) scattering mechanisms, such as reflections and diffractions,
      a buried cuboid possessing straight edges is chosen as the buried target in this
      paper. By performing an inverse discrete Fourier transform (IDFT) on the wideband
      backscattered field data computed with an accurate and fast EM method, the 1-D
      range profiles of the buried cuboid is successfully simulated. The simulated
      range profiles provide information about the position and scattering strength of
      the cuboid's scattering centers along the range direction. Meanwhile, a predicted
      distribution of the scattering centers is quantitatively calculated for the
      buried cuboid based on the ray path computation. Good agreement has been found
      between simulated and predicted locations of the range profiles. Validation for
      amplitudes of the range profiles is further provided in the research. Both the
      peak amplitudes and locations of the range profiles could be understood and
      analyzed based on the knowledge of the scattering mechanisms. The formation of
      the 1-D range profiles has been revealed clearly from the full analysis of the
      scattering mechanisms and contributions. The problem has been solved for both
      near and far field regions. Finally, the buried depth and the characteristic size
      of the object are reasonably deduced from the simulated range profiles.

PMID- 21716467
TI  - Dynamic parabolic pulse generation using temporal shaping of wavelength to time
      mapped pulses.
AB  - Self-phase modulation in fiber amplifiers can significantly degrade the quality
      of compressed pulses in chirped pulse amplification systems. Parabolic pulses
      with linear frequency chirp are suitable for suppressing nonlinearities, and to
      achieve high peak power pulses after compression. In this paper, we present an
      active time domain technique to generate parabolic pulses for chirped pulse
      amplification applications. Pulses from a mode-locked laser are temporally
      stretched and launched into an amplitude modulator, where the drive voltage is
      designed using the spectral shape of the input pulse and the transfer function of
      the modulator, resulting in the generation of parabolic pulses. Experimental
      results of pulse shaping with a pulse train from a mode-locked laser are
      presented, with a residual error of less than 5%. Moreover, an extinction ratio
      of 27 dB is achieved, which is ideal for chirped pulse amplification
      applications.

PMID- 21716468
TI  - True-time delay line with separate carrier tuning using dual-parallel MZM and
      stimulated Brillouin scattering-induced slow light.
AB  - We experimentally demonstrate a novel tunable true-time delay line with separate
      carrier tuning using dual-parallel Mach-Zehnder modulator and stimulated
      Brillouin scattering-induced slow light. The phase of the optical carrier can be
      continuously and precisely controlled by simply adjusting the dc bias of the dual
      parallel Mach-Zehnder modulator. In addition, both the slow light and single
      sideband modulation can be simultaneously achieved in the stimulated Brillouin
      scattering process with three types of configuration. Finally, the true-time
      delay technique is clearly verified by a two-tap incoherent microwave photonic
      filter as the free spectral range of the filter is changed.

PMID- 21716469
TI  - Arm-edge conditions in plasmonic folded dipole nanoantennas.
AB  - Silver folded dipoles consisting of two parallel nanowires may operate as
      efficient transmitting and receiving nanoantennas in the optical domain in both
      cases of silver-nanowire-terminated arm-edges and open-terminated arm-edges, in
      contrast to their conventional radio-frequency (RF) counterparts that only
      operate efficiently when they are short-wire-terminated arm-edges. The mode
      decomposition analysis with the equivalent circuit reveals that the difference of
      the wave numbers between the common and the differential modes allows this
      feature for the optical folded dipole nanoantenna under both arm-edge conditions.
      The analysis also estimates the efficiency of the folded dipoles via the
      equivalent radius of nanowires for the common mode. These folded nanostructures
      may exhibit the enhanced efficiency with the maintained radiation patterns, where
      the efficiency of folded dipoles is the same as that of the effective single
      dipole at resonance.

PMID- 21716470
TI  - Modifying photoisomerization efficiency by metallic nanostructures.
AB  - Trans-to-cis photoisomerization efficiency of azobenzene dye is artificially
      modified from 0.09 to 0.38 when dye molecules are placed close to gold
      nanoparticle films with different structures. Transient fluorescence and surface
      enhanced Raman scattering measurement verify that the enhancement and reduction
      of photoisomerization efficiency come from the competition between enhanced local
      optical field from surface plasmon resonance and the accelerated nonradiative
      decay of excited dye molecules. The photoisomerization efficiency can be further
      modified by controlling the distance between azobenzene dye and gold films. Our
      finding can be applied to improve the performance of photoisomerization effect in
      photochemistry and photonics.

PMID- 21716471
TI  - Superfocusing of electric or magnetic fields using conical metal tips: effect of
      mode symmetry on the plasmon excitation method.
AB  - We compare single- and double-sided excitation methods of adiabatic surface
      plasmon polariton (SPP) wave superfocusing for scattering-type metallic near
      field scanning optical microscopy (s-NSOM). Using the results of full 3D finite
      difference time domain analyses, the differences in field enhancement factors are
      explained and reveal the mode selectivity of a conical NSOM tip for adiabatic SPP
      superfocusing. Exploiting the mode-symmetric nature of the tip further, we also
      show that it is possible to selectively confine either the electric or magnetic
      field at the NSOM tip apex, by simply adjusting the relative phase between the
      SPP waves in the double-sided excitation approach.

PMID- 21716472
TI  - A broadband zone plate lens from transformation optics.
AB  - A zone plate lens utilizing a refractive instead of diffractive approach is
      presented for broadband operation. By utilizing transformation optics, we
      compress the conventional hyperbolic lens into a flat one with a few zone plates
      made of all-dielectric materials. Such a transformed lens maintains the broadband
      performance of the original lens, thus providing a superior alternative to the
      diffractive Fresnel element which is inherently narrow band.

PMID- 21716473
TI  - High resolution on-chip spectroscopy based on miniaturized microdonut resonators.
AB  - We experimentally demonstrate a high resolution integrated spectrometer on
      silicon on insulator (SOI) substrate using a large-scale array of microdonut
      resonators. Through top-view imaging and processing, the measured spectral
      response of the spectrometer shows a linewidth of ~0.6 nm with an operating
      bandwidth of ~50 nm. This high resolution and bandwidth is achieved in a compact
      size using miniaturized microdonut resonators (radius ~2 MUm) with a high quality
      factor, single-mode operation, and a large free spectral range. The
      microspectrometer is realized using silicon process compatible fabrication and
      has a great potential as a high-resolution, large dynamic range, light-weight,
      compact, high-speed, and versatile microspectrometer.

PMID- 21716474
TI  - Visualization of surface plasmon polariton waves in two-dimensional plasmonic
      crystal by cathodoluminescence.
AB  - A cathodoluminescence technique using a 200-keV transmission electron microscope
      revealed the dispersion patterns of surface plasmon polaritons (SPPs) in a two
      dimensional plasmonic crystal with cylindrical hole arrays. The dispersion curves
      of the SPP modes involving the Gamma point were derived from the angle-resolved
      spectrum patterns. The contrast along the dispersion curves changed with the
      polarization direction of the emitted light due to the property of the SPP modes.
      The SPP modes at the Gamma point were identified from the photon maps, which
      mimicked standing SPP waves in a real space. The beam-scan spectral images across
      the plasmonic crystal edge clearly demonstrated the dependence of the SPP to
      light conversion efficiency on the emission angle and polarization of light.

PMID- 21716475
TI  - Nanoscale heating of laser irradiated single gold nanoparticles in liquid.
AB  - Biological applications where nanoparticles are used in a cell environment with
      laser irradiation are rapidly emerging. Investigation of the localized heating
      effect due to the laser irradiation on the particle is required to preclude
      unintended thermal effects. While bulk temperature rise can be determined using
      macroscale measurement methods, observation of the actual temperature within the
      nanoscale domain around the particle is difficult and here we propose a method to
      measure the local temperature around a single gold nanoparticle in liquid, using
      white light scattering spectroscopy. Using 40-nm-diameter gold nanoparticles
      coated with thermo-responsive polymer, we monitored the localized heating effect
      through the plasmon peak shift. The shift occurs due to the temperature-dependent
      refractive index change in surrounding polymer medium. The results indicate that
      the particle experiences a temperature rise of around 10 degrees Celsius when
      irradiated with tightly focused irradiation of ~1 mW at 532 nm.

PMID- 21716476
TI  - Phase synchronization scheme for a practical phase sensitive amplifier of ASK-NRZ
      signals.
AB  - We present a phase locking scheme that enables the demonstration of a practical
      dual pump degenerate phase sensitive amplifier for 10 Gbit/s non-return to zero
      amplitude shift keying signals. The scheme makes use of cascaded Mach Zehnder
      modulators for creating the pump frequencies as well as of injection locking for
      extracting the signal carrier and synchronizing the local lasers. An in depth
      optimization study has been performed, based on measured error rate performance,
      and the main degradation factors have been identified.

PMID- 21716477
TI  - Ultra-wideband optical leaky-wave slot antennas.
AB  - We propose and investigate an ultra-wideband leaky-wave antenna that operates at
      optical frequencies for the purpose of efficient energy coupling between
      localized nanoscale optical circuits and the far-field. The antenna consists of
      an optically narrow aluminum slot on a silicon substrate. We analyze its far
      field radiation pattern in the spectral region centered around 1550 nm with a 50%
      bandwidth ranging from 2000 nm to 1200 nm. This plasmonic leaky-wave slot
      produces a maximum far-field radiation angle at 32 degrees  and a 3 dB beamwidth
      of 24 degrees  at its center wavelength. The radiation pattern is preserved
      within the 50% bandwidth suffering only insignificant changes in both the
      radiation angle and the beamwidth. This wide-band performance is quite unique
      when compared to other optical antenna designs. Furthermore, the antenna
      effective length for radiating 90% and 99.9% of the input power is only
      0.5lambda(0) and 1.5lambda(0) respectively at 1550 nm. The versatility and
      simplicity of the proposed design along with its small footprint makes it
      extremely attractive for integration with nano-optical components using existing
      technologies.

PMID- 21716478
TI  - Tunable complex-valued multi-tap microwave photonic filter based on single
      silicon-on-insulator microring resonator.
AB  - A complex-valued multi-tap tunable microwave photonic filter based on single
      silicon-on-insulator microring resonator is presented. The degree of tunability
      of the approach involving two, three and four taps is theoretical and
      experimentally characterized, respectively. The constraints of exploiting the
      optical phase transfer function of a microring resonator aiming at implementing
      complex-valued multi-tap filtering schemes are also reported. The trade-off
      between the degree of tunability without changing the free spectral range and the
      number of taps is studied in-depth. Different window based scenarios are
      evaluated for improving the filter performance in terms of the side-lobe level.

PMID- 21716479
TI  - Second harmonic generation in AlGaAs photonic wires using low power continuous
      wave light.
AB  - We report modal phase matched (MPM) second harmonic generation (SHG) in high
      index contrast AlGaAs sub-micron ridge waveguides, by way of sub-mW continuous
      wave powers at telecommunication wavelengths. We achieve an experimental
      normalized conversion efficiency of ~14%/W/cm2, obtained through a careful sub
      wavelength design supporting both the phase matching requirement and a
      significant overlap efficiency. Furthermore, the weak anomalous dispersion,
      robust fabrication technology and possible geometrical and thermal tuning of the
      device functionality enable a fully integrated multi-functional chip for several
      critical areas in telecommunications, including wavelength (time) division
      multiplexing and quantum entanglement.

PMID- 21716480
TI  - Fiber-tip micro-cavity for temperature and transverse load sensing.
AB  - A low cost fiber-optic micro-cavity interferometric sensor is presented. The
      micro-cavity is fabricated at the fiber tip by splicing a silica capillary to a
      single mode fiber and then heating/melting the capillary to form a microsphere
      with an internal air cavity. Applications of the micro-cavity sensor for
      temperature and traverse load measurements are demonstrated. The sensor has small
      size and good mechanical strength, and may be used in high temperature
      environment.

PMID- 21716481
TI  - Simultaneous all-optical demodulation and format conversion for multi-channel
      (CS)RZ-DPSK signals.
AB  - We proposed and demonstrate an all-optical demodulation and format conversion
      scheme for multi-channel (carrier suppressed) return-to-zero differential phase
      shift keying ((CS)RZ-DPSK) signals. By utilizing a single delay interferometer
      (DI) with half bit delay, multi-channel (CS)RZ-DPSK signals can be demodulated
      simultaneously at the destructive port of the DI, with the corresponding
      converted nonreturn-to-zero differential phase shift keying (NRZ-DPSK) signals
      obtained at the constructive port. The proposed multi-channel operation has been
      demonstrated for 6*20 Gb/s RZ-DPSK and 6*40 Gb/s CSRZ-DPSK signals, with ~0.8 and
      1.2 dB average power penalties for the format conversions respectively.

PMID- 21716482
TI  - Novel technique for mode selection in a multimode fiber laser.
AB  - A simple technique for transverse mode selection in a large-mode-area (multimode)
      fiber laser is described. The technique exploits the different spectral responses
      of feedback elements based on a fiber Bragg grating and a volume Bragg grating to
      achieve wavelength-dependent mode filtering. This approach has been applied to a
      cladding-pumped thulium-doped fiber laser with a multimode core to achieve a
      single-spatial-mode output beam with a beam propagation factor (M2) of 1.05 at
      1923 nm. Without mode selection the free-running fiber laser has a multimode
      output beam with an M2 parameter of 3.3. Selective excitation of higher order
      modes is also possible via the technique and preliminary results for laser
      oscillation on the LP11 mode are also discussed along with the prospects for
      scaling to higher power levels.

PMID- 21716483
TI  - Compact highly-nonlinear AlGaAs waveguides for efficient wavelength conversion.
AB  - We report on the efficient nonlinear optical interactions in AlGaAs strip-loaded
      waveguides with a wafer composition specifically designed to increase the
      nonlinear coefficient. We demonstrate a broad-band self-phase modulation with a
      nonlinear phase shift up to 6pi, and four-wave mixing with a 20-nm tuning range
      and signal-to-idler conversion efficiency up to 10 dB. Our samples are several
      times shorter than similar devices used for wavelength conversion by XPM and FWM
      in previous reports, but the efficiency of the observed effects is similar. Our
      experimental studies demonstrate the high potential of AlGaAs for all-optical
      networks.

PMID- 21716484
TI  - Continuously tunable optical buffer with a dual silicon waveguide design.
AB  - We propose a design for an optical buffer that comprises two coupled silicon
      waveguides, which is capable of generating a large continuously tunable change in
      the propagation delay time. The optical delay can be varied by more than 100%
      through varying the spacing between the waveguides.

PMID- 21716485
TI  - Planar waveguide tilted Bragg grating refractometer fabricated through physical
      micromachining and direct UV writing.
AB  - A set of rapid prototyping techniques are combined to construct a laterally
      tilted Bragg grating refractometer in a novel planar geometry. The tilted Bragg
      grating is fabricated in a silica-on-silicon planar substrate using a dual beam
      direct UV writing (DUW) technique. Lateral cladding mode confinement is
      subsequently achieved by physically micromachining two trenches either side of
      the direct UV written waveguide. The resulting device is demonstrated as an
      effective refractometer, displaying a comparable sensitivity to tilted Bragg
      gratings in a fiber optical geometry, but with the added advantages of planar
      integration.

PMID- 21716486
TI  - Modulated near-field spectral extraction of broadband mid-infrared signals with a
      ceramic light source.
AB  - In order to obtain broadband near-field infrared (IR) spectra, a Fourier
      transform IR spectrometer (FT-IR) and a ceramic light source were used with a
      scattering-type scanning near-field optical microscope (s-SNOM). To suppress the
      background (far-field) scattering, the distance between the scattering probe and
      the sample was modulated with frequency Omega by a piezo-electric actuator, and
      the Omega component was extracted from the signal with a lock-in detection. With
      Omega=30 kHz, a peak-to-peak modulation amplitude of 198 nm, and a probe with
      smooth surface near the tip, broadband near-field IR spectra could be obtained in
      the 1200-2500 cm(-1).

PMID- 21716487
TI  - Selective tuning of high-Q silicon photonic crystal nanocavities via laser
      assisted local oxidation.
AB  - We examine the cavity resonance tuning of high-Q silicon photonic crystal
      heterostructures by localized laser-assisted thermal oxidation using a 532 nm
      continuous wave laser focused to a 2.5 MUm radius spot-size. The total shift is
      consistent with the parabolic rate law. A tuning range of up to 8.7 nm is
      achieved with ~ 30 mW laser powers. Over this tuning range, the cavity Qs
      decreases from 3.2*10(5) to 1.2*10(5). Numerical simulations model the
      temperature distributions in the silicon photonic crystal membrane and the cavity
      resonance shift from oxidation.

PMID- 21716488
TI  - Second harmonic generation of swift carbon ion irradiated Nd:GdCOB waveguides.
AB  - We report on the second harmonic generation at ~532 nm of optical waveguides in
      Nd:GdCOB produced by swift carbon ion irradiation. The fabricated waveguide shows
      good guiding property. Under pump of ~1064-nm fundamental light, the optical
      conversion efficiency of the frequency doubling is 0.48% W(-1) and 6.8% W(-1) for
      continuous wave and pulsed laser beams, respectively.

PMID- 21716489
TI  - Nanoscale interlayer that raises response rate in photorefractive liquid crystal
      polymer composites.
AB  - By depositing a nanoscale photoconductive layer on a stable photorefractive (PR)
      polymeric film, consisting of the polymer poly[N-vinylcarbazole] (PVK) doped with
      4,4'-n-pentylcyanobiphenyl (5CB) and C60, both the response rate and beam
      coupling properties were improved greatly. Systematic measurements and
      observations unveiled the role played by the additive layer in preventing ion
      injection from the ITO layer into the PR film and hence in mitigating the charge
      compensation. A strong fanning effect and high diffraction orders at small angles
      have demonstrated the excellent PR property in the modified samples used. To
      demonstrate great potential of the PR composite in the updatable applications,
      real time double exposure interferometry was performed accordingly with good
      results.

PMID- 21716490
TI  - Channel waveguide lasers in Nd:GGG crystals fabricated by femtosecond laser
      inscription.
AB  - Buried channel waveguides have been fabricated in Nd:GGG crystals by using the
      femtosecond laser inscription. The waveguides are confined between two filaments
      with propagation losses of 2.0 dB/cm. Stable continuous wave laser oscillation at
      ~1061 nm has been demonstrated at room temperature. Under 808 nm optical
      excitation, a pump threshold of 29 mW and a slope efficiency of 25% have been
      obtained.

PMID- 21716491
TI  - Contact-free fault location and imaging with on-chip terahertz time-domain
      reflectometry.
AB  - We demonstrate in a first experimental study the application of novel micro
      machined optoelectronic probes for a time-domain reflectometry-based localization
      of discontinuities and faults in electronic structures at unprecedented
      resolution and accuracy (+/- 0.55 um). Thanks to the THz-range bandwidth of our
      optoelectronic system--including the active probes used for pulse injection and
      detection--the spatial resolution and precision of high-end all-electronic
      detection systems is surpassed by more than one order of magnitude. The new
      analytic technology holds great promise for rapid and precise fault detection and
      location in advanced (3D) integrated semiconductor chips and packages.

PMID- 21716492
TI  - 40-Gb/s FSK modulated WDM-PON with variable-rate multicast overlay.
AB  - This paper proposes a novel conjugate-driven frequency shift keying (FSK)
      modulated wavelength division multiplexing passive network (WDM-PON) with
      variable-rate multicast services. Optical orthogonal frequency division
      multiplexing (OFDM) is adopted for multicast overlay services with different rate
      requirements. A differential detection is used for the demodulation of FSK
      signal, which can eliminate the crosstalk from the OFDM signal. A total 40-Gb/s
      FSK point to point (P2P) signal and 6.3-Gb/s OFDM overlay with three kinds of
      variable-rate multicast services are experimentally demonstrated. A physical
      layer adaptive identification is proposed for the variable-rate multicast
      services. After 25 km single mode fiber (SMF) transmission, the power penalties
      of FSK P2P signal and OFDM multicast overlay are 1.3 dB and 1.7 dB respectively.

PMID- 21716493
TI  - Surface plasmon polariton amplification in metal-semiconductor structures.
AB  - We propose a novel scheme of surface plasmon polariton (SPP) amplification that
      is based on a minority carrier injection in a Schottky diode. This scheme uses
      compact electrical pumping instead of bulky optical pumping. Compact size and a
      planar structure of the proposed amplifier allow one to utilize it in integrated
      plasmonic circuits and couple it easily to passive plasmonic devices. Moreover,
      this technique can be used to obtain surface plasmon lasing.

PMID- 21716494
TI  - Demonstration of Zeno switching through inverse Raman scattering in an optical
      fiber.
AB  - We report the observation of Zeno switching through an inverse Raman scattering
      (IRS) process in an optical fiber. In IRS, light at the anti-Stokes frequency is
      strongly attenuated in the presence of a pump field, allowing it to be used for
      all-optical switching and modulation. Our observed level of induced absorption
      via IRS in the optical fiber is > 20 dB in a time scale of less than 5 ps. The
      full Raman response spectrum was extracted experimentally and excellent agreement
      was found between the experimental data and theoretical modeling of IRS.

PMID- 21716495
TI  - Preconditioning for multiplexed imaging with spatially coded PSFs.
AB  - We propose a preconditioning method to improve the convergence of iterative
      reconstruction algorithms in multiplexed imaging based on convolution-based
      compressive sensing with spatially coded point spread functions (PSFs). The
      system matrix is converted to improve the condition number with a preconditioner
      matrix. The preconditioner matrix is calculated by Tikhonov regularization in the
      frequency domain. The method was demonstrated with simulations and an experiment
      involving a range detection system with a grating based on the multiplexed
      imaging framework. The results of the demonstrations showed improved
      reconstruction fidelity by using the proposed preconditioning method.

PMID- 21716496
TI  - Real-time in situ Mueller matrix ellipsometry of GaSb nanopillars: observation of
      anisotropic local alignment.
AB  - The formation of GaSb nanopillars by low energy ion sputtering is studied in real
      time by spectroscopic Mueller matrix ellipsometry, from the initial formation in
      the smooth substrate until nanopillars with a height of 200-300 nm are formed. As
      the nanopillar height increased above 100 nm, coupling between orthogonal
      polarization modes was observed. Ex situ angle resolved Mueller polarimetry
      measurements revealed a 180 degrees  azimuth rotation symmetry in the off
      diagonal Mueller elements, which can be explained by a biaxial material with
      different dielectric functions epsilonx and epsilony in a plane parallel to the
      substrate. This polarization coupling can be caused by a tendency for local
      direction dependent alignment of the pillars, and such a tendency is confirmed by
      scanning electron microscopy. Such observations have not been made for GaSb
      nanopillars shorter than 100 nm, which have optical properties that can be
      modeled as a uniaxial effective medium.

PMID- 21716497
TI  - Double-clad hollow core photonic crystal fiber for coherent Raman endoscope.
AB  - Performing label free coherent anti-Stokes Raman scattering (CARS) and stimulated
      Raman scattering (SRS) in endoscope imaging is a challenge, with huge potential
      clinical benefit. To date, this goal has remained inaccessible because of the
      inherent coherent Raman noise that is generated in the fiber itself. By
      developing double-clad hollow core photonic crystal fiber, we demonstrate
      coherent anti-Stokes Raman scattering and stimulated Raman scattering in an
      'endoscope-like' scheme. Both the excitation beams and the collected CARS and SRS
      signals travel through the same fiber. No CARS and SRS signals are generated
      within the hollow core fiber even for temporally overlapping pump and Stokes
      beams, leading to excellent image quality. The CARS and SRS signals generated in
      the sample are coupled back into a high numerical aperture multimode cladding
      surrounding the central photonic crystal cladding. We demonstrate this scheme by
      imaging molecular vibrational bonds of organic crystal deposited on a glass
      surface.

PMID- 21716498
TI  - Design and comparison of GaAs, GaAsP and InGaAlAs quantum-well active regions for
      808-nm VCSELs.
AB  - Vertical-cavity surface-emitting lasers emitting at 808 nm with unstrained
      GaAs/Al0.3Ga0.7As, tensilely strained GaAs(x)P(1-x)/Al0.3Ga0.7As and
      compressively strained In(1-x-y)Ga(x)Al(y)As/Al0.3Ga0.7As quantum-well active
      regions have been investigated. A comprehensive model is presented to determine
      the composition and width of these quantum wells. The numerical simulation shows
      that the gain peak wavelength is near 800 nm at room temperature for GaAs well
      with width of 4 nm, GaAs0.87P0.13 well with width of 13 nm and
      In0.14Ga0.74Al0.12As well with width of 6 nm. Furthermore, the output
      characteristics of the three designed quantum-well VCSELs are studied and
      compared. The results indicate that In0.14Ga0.74Al0.12As is the most appropriate
      candidate for the quantum well of 808-nm VCSELs.

PMID- 21716499
TI  - A vector boundary matching technique for efficient and accurate determination of
      photonic bandgaps in photonic bandgap fibers.
AB  - A vector boundary matching technique has been proposed and demonstrated for
      finding photonic bandgaps in photonic bandgap fibers with circular nodes. Much
      improved accuracy, comparing to earlier works, comes mostly from using more
      accurate cell boundaries for each mode at the upper and lower edges of the band
      of modes. It is recognized that the unit cell boundary used for finding each mode
      at band edges of the 2D cladding lattice is not only dependent on whether it is a
      mode at upper or lower band edge, but also on the azimuthal mode number and
      lattice arrangements. Unit cell boundaries for these modes are determined by mode
      symmetries which are governed by the azimuthal mode number as well as lattice
      arrangement due to mostly geometrical constrains. Unit cell boundaries are
      determined for modes at both upper and lower edges of bands of modes dominated by
      m = 1 and m = 2 terms in their longitudinal field Fourier-Bessel expansion
      series, equivalent to LP0s and LP1s modes in the approximate LP mode
      representations, for hexagonal lattice to illustrate the technique. The novel
      technique is also implemented in vector form and incorporates a transfer matrix
      algorithm for the consideration of nodes with arbitrary refractive index
      profiles. Both are desired new capabilities for further explorations of advanced
      new designs of photonic bandgap fibers.

PMID- 21716500
TI  - Parallel lensless optical correlator based on two phase-only spatial light
      modulators.
AB  - In this paper, we proposed a parallel phase-only lensless optical correlator
      based on two pieces of Liquid Crystal on Silicon Spatial Light Modulators. Phase
      Fresnel Lens Array and specialized grating are implemented to realize multi
      channel and multiplexed LOC. Experimental results of Chinese characters'
      recognitions are given as demonstration of proposed technique. High uniformity of
      processing channels has been verified by autocorrelation process of four same
      Chinese characters. The technique is programmable and adjustment of optical path
      could be realized without changing of optical setup. The implementations could be
      performed on the same configuration as single channel optical correlator without
      mechanical alternation.

PMID- 21716501
TI  - Multispectral Cerenkov luminescence tomography for small animal optical imaging.
AB  - Quite recently Cerenkov luminescence imaging (CLI) has been introduced as a novel
      pre-clinical imaging for the in vivo imaging of small animals such as mice. The
      CLI method is based on the detection of Cerenkov radiation (CR) generated by beta
      particles as they travel into the animal tissues with an energy such that
      Cerenkov emission condition is satisfied. This paper describes an image
      reconstruction method called multi spectral diffuse Cerenkov luminescence
      tomography (msCLT) in order to obtain 3D images from the detection of CR. The
      multispectral approach is based on a set of 2D planar images acquired using a
      number of narrow bandpass filters, and the distinctive information content at
      each wavelength is used in the 3D image reconstruction process. The proposed
      msCLT method was tested both in vitro and in vivo using 32P-ATP and all the
      images were acquired by using the IVIS 200 small animal optical imager (Caliper
      Life Sciences, Alameda USA). Source depth estimation and spatial resolution
      measurements were performed using a small capillary source placed between several
      slices of chicken breast. The theoretical Cerenkov emission spectrum and optical
      properties of chicken breast were used in the modelling of photon propagation. In
      vivo imaging was performed by injecting control nude mice with 10 MBq of 32P-ATP
      and the 3D tracer bio-distribution was reconstructed. Whole body MRI was acquired
      to provide an anatomical localization of the Cerenkov emission. The spatial
      resolution obtained from the msCLT reconstructed images of the capillary source
      showed that the FWHM is about 1.5 mm for a 6 mm depth. Co-registered MRI images
      showed that the Cerenkov emission regions matches fairly well with anatomical
      regions, such as the brain, heart and abdomen. Ex vivo imaging of the different
      organs such as intestine, brain, heart and ribs further confirms these findings.
      We conclude that in vivo 3D bio-distribution of a pure beta-minus emitting
      radiopharmaceutical such as 32P-ATP can be obtained using the msCLT
      reconstruction approach.

PMID- 21716502
TI  - Stand-up magnetic metamaterials at terahertz frequencies.
AB  - We present a detailed study of non-planar or 'stand-up' split ring resonators
      operating at terahertz frequencies. Based on a facile multilayer electroplating
      fabrication, this technique can create large area split ring resonators on both
      rigid substrates and conformally compliant structures. In agreement with
      simulation results, the characterization of these metamaterials shows a strong
      response induced purely by the magnetic field. The retrieved parameters also
      exhibit negative permeability values over a broad frequency span. The extracted
      parameters exhibit bianisotropy due to the symmetry breaking of the substrate,
      and this effect is investigated for both single and broad side coupled split
      rings. Our 3D metamaterial examples pave the way towards numerous potential
      applications in the terahertz region of the spectrum.

PMID- 21716503
TI  - Multichannel Fourier-transform interferometry for fast signals.
AB  - Multichannel Fourier transform interferometry to measure the spectrum of
      arbitrarily short pulses and of fast time-varying signals was achieved using a
      micro/nanomanufactured multimirror array. We describe the performance of a
      demonstrator FTIR that works in the mid-infrared (MIR) range of 700-1400 cm(-1)
      and reaches a spectral resolution of 10 cm(-1) taking into account apodization.
      Spectral measurements down to pulse lengths of 319 us were carried out using a
      mechanical camera shutter. Arbitrarily short pulses are expected feasible
      provided the source can deliver enough photons to overcome the noise equivalent
      number of photons.

PMID- 21716505
TI  - Comparison of photodiode nonlinearity measurement systems.
AB  - Photodiode nonlinearity measurements using one-, two- and three-tone measurement
      systems are compared with each other, to investigate the comparison accuracy
      between setups. The mathematical relationship between each setup is analyzed, and
      data on multiple devices are compared to find under which conditions the
      measurements are comparable. It is shown that the three measurement systems can
      be used interchangeably only when the distortion adheres to the expected
      mathematical slopes.

PMID- 21716506
TI  - Silicon-on-insulator polarization splitting and rotating device for polarization
      diversity circuits.
AB  - A compact and efficient polarization splitting and rotating device built on the
      silicon-on-insulator platform is introduced, which can be readily used for the
      interface section of a polarization diversity circuit. The device is compact,
      with a total length of a few tens of microns. It is also simple, consisting of
      only two parallel silicon-on-insulator wire waveguides with different widths, and
      thus requiring no additional and nonstandard fabrication steps. A total insertion
      loss of -0.6 dB and an extinction ratio of 12 dB have been obtained
      experimentally in the whole C-band.

PMID- 21716507
TI  - Fabrication of phase-change Ge2Sb2Te5 nano-rings.
AB  - Phase-change material Ge2Sb2Te5 rings with nanometer-scale thickness have been
      fabricated using the photo-thermal effect of a focused laser beam followed by
      differential chemical etching. Laser irradiation conditions and etching process
      parameters are varied to control the geometric characteristics of the rings. We
      demonstrate the possibility of arranging the rings in specific geometric
      patterns, and also their release from the original substrate.

PMID- 21716508
TI  - High-performance GaN metal-insulator-semiconductor ultraviolet photodetectors
      using gallium oxide as gate layer.
AB  - In this study, gallium nitride (GaN)-based metal-insulator-semiconductor (MIS)
      ultraviolet (UV) photodetectors (PDs) with a gallium oxide (GaO(x)) gate layer
      formed by alternating current bias-assisted photoelectrochemical oxidation of n
      GaN are presented. By introducing the GaO(x) gate layer to the GaN MIS UV PDs,
      the leakage current is reduced and a much larger UV-to-visible rejection ratio
      (R(UV/vis)) of spectral responsivity is achieved. In addition, a bias-dependent
      spectral response results in marked increase of the R(UV/vis) with bias voltage
      up to ~10(5). The bias-dependent responsivity suggests the possible existence of
      internal gain in of the GaN MIS PDs.

PMID- 21716509
TI  - Novel fiber Bragg grating fabrication system for long gratings with independent
      apodization and with local phase and wavelength control.
AB  - We proposed and demonstrated a novel practical fiber Bragg grating (FBG)
      fabrication setup constructed with high performance linear stages, piezoelectric
      translation (PZT) stages, and a highly stable continuous wave laser. The FBG
      fabrication system enables writing of long FBGs by a continuous translate-and
      write process and allows implementation of arbitrary chirp and apodization. A key
      innovation is that the local Bragg wavelength is controlled by a simple movement
      of the phase mask by a PZT in the direction perpendicular to its surface. The
      focus position of the two writing beams is not changed during the Bragg
      wavelength change, an intrinsic feature of the design, ensuring simplicity,
      robustness and stability. Apodization can be achieved by vibrating the phase mask
      in the direction parallel to its surface by a PZT. Phase steps can also be
      inserted in FBGs at any desired locations by stepping the same PZT. A long
      uniform FBG and a linearly chirped FBG are written to demonstrate the performance
      of the setup.

PMID- 21716510
TI  - Mode multiplexer for multimode transmission in multimode fibers.
AB  - We have numerically demonstrated an efficient mode multiplexer which can tailor
      the input field patterns by using a phase controller and a mode coupler formed by
      four single-mode fibers (SMFs). By connecting the mode multiplexer to a multimode
      fiber (MMF), two orthogonal higher-order modes of the MMF can be simultaneously
      excited to form two communication channels. The simulated results show that very
      low modal interference between the two excited modes can be achieved by using the
      proposed mode multiplexer. We have also discussed the effect of the distance and
      size of the SMFs in the mode coupler on the performance of the proposed mode
      multiplexer.

PMID- 21716511
TI  - Effects of a silicon probe on gold nanoparticles on glass under evanescent
      illumination.
AB  - We have numerically investigated the influence of a nanoscale silicon tip in
      proximity to an illuminated gold nanoparticle. We describe how the position of
      the high-permittivity tip and the size of the nanoparticle impact the absorption,
      peak electric field and surface plasmon resonance wavelength under different
      illumination conditions. We detail the finite element method (FEM) approach we
      have used, whereby we specify a volume excitation field analytically and
      calculate the difference between this source field and the total field (i.e.,
      scattered-field formulation). We show that a nanoscale tip can locally enhance
      the absorption of the particle as well as the peak electric field at length
      scales far smaller than the wavelength of the incident light.

PMID- 21716512
TI  - Overcoming the losses of a split ring resonator array with gain.
AB  - We present a computational approach, allowing for a self-consistent treatment of
      a split ring resonator (SRR) array with a gain layer underneath. We apply three
      different pumping schemes on the gain layer: (1) homogeneously pumped isotropic
      gain, (2) homogeneously pumped isotropic gain with a shadow cast by the SRR and
      (3) anisotropic gain pumped in a selected direction only. We show numerically the
      magnetic losses of the SRR can be compensated by the gain. The difference on loss
      compensations among the three pumping schemes is analyzed by the electric field
      distribution. Studies also show the dielectric background of gain does not affect
      the loss compensation much for the gain only pumped in the direction parallel to
      the SRR plane.

PMID- 21716513
TI  - Measurements of 3D relative locations of particles by Fourier Interferometry
      Imaging (FII).
AB  - In a large number of physical systems formed of discrete particles, a key
      parameter is the relative distance between the objects, as for example in studies
      of spray evaporation or droplets micro-explosion. This paper is devoted to the
      presentation of an approach where the relative 3D location of particles in the
      control volume is accurately extracted from the interference patterns recorded at
      two different angles. No reference beam is used and only ten (2 + 8) 2D-FFT have
      to be computed.

PMID- 21716514
TI  - Enhanced output power of GaN-based LEDs with embedded AlGaN pyramidal shells.
AB  - In this article, the characteristics of GaN-based LEDs grown on Ar-implanted GaN
      templates to form inverted Al0.27Ga0.83N pyramidal shells beneath an active layer
      were investigated. GaN-based epitaxial layers grown on the selective Ar-implanted
      regions had lower growth rates compared with those grown on the implantation-free
      regions. This resulted in selective growth, and formation of V-shaped concaves in
      the epitaxial layers. Accordingly, the inverted Al0.27Ga0.83N pyramidal shells
      were formed after the Al0.27Ga0.83N and GaN layers were subsequently grown on the
      V-shaped concaves. The experimental results indicate that the light-output power
      of LEDs with inverted AlGaN pyramidal shells was higher than those of
      conventional LEDs. With a 20 mA current injection, the output power was enhanced
      by 10% when the LEDs were embedded with inverted Al0.27Ga0.83N pyramidal shells.
      The enhancement in output power was primarily due to the light scattering at the
      Al0.27Ga0.83N/GaN interface, which leads to a higher escape probability for the
      photons, that is, light-extraction efficiency. Based on the ray tracing
      simulation, the output power of LEDs grown on Ar-implanted GaN templates can be
      enhanced by over 20% compared with the LEDs without the embedded AlGaN pyramidal
      shells, if the AlGaN layers were replaced by Al0.5Ga0.5N layers.

PMID- 21716515
TI  - Reconfigurable silicon thermo-optical device based on spectral tuning of ring
      resonators.
AB  - A novel tunable and reconfigurable thermo-optical device is theoretically
      proposed and analyzed in this paper. The device is designed to be entirely
      compatible with CMOS process and to work as a thermo-optical filter or modulator.
      Numerical results, made by means of analytical and Finite-Difference Time-Domain
      (FDTD) methods, show that a compact device enables a broad bandwidth operation,
      of up to 830 GHz, which allows the device to work under a large temperature
      variation, of up to 96 K.

PMID- 21716516
TI  - Real-time OFDM transmitter beyond 100 Gbit/s.
AB  - Real-time OFDM transmitters breaking the 100 Gbit/s barrier require high
      performance, usually FPGA-based digital signal processing. Especially the Fourier
      transform as a key operation of any OFDM system must be optimized with respect to
      performance and chip area utilization. Here, we demonstrate an alternative to the
      widely adopted fast Fourier transform algorithm. Based on an extensive yet
      optimized use of pre-set look-up tables, our FPGA implementation supports fast
      reconfigurable channel equalization and switching times in the nanosecond range
      without re-loading any code. We demonstrate the potential of the concept by
      realizing the first real-time single polarization OFDM transmitter generating a
      101.5 Gbit/s data stream by modulating 58 subcarriers with 16QAM.

PMID- 21716517
TI  - Electro-optic polymer spatial light modulator based on a Fabry-Perot
      interferometer configuration.
AB  - A spatial light modulator (SLM) based on a Fabry-Perot interferometer
      configuration has been fabricated and tested. The Fabry-Perot spacer layer is a
      thin film of the SEO100 electro-optic polymer which serves as the nonlinear
      medium. Measurement results demonstrate the modulation of multiple pixels
      operating simultaneously at frequencies ranging from 300 kHz to 800 kHz which is
      significantly faster than SLMs based on liquid crystal and digital micromirror
      device technology. An average modulation contrast of 50% for all pixels is
      achieved with a drive voltage of 70 V(rms) at 100 kHz. Microwave speeds and CMOS
      compatibility are feasible with improved transmission line and cavity design.

PMID- 21716518
TI  - Causality-based method for determining the time origin in terahertz emission
      spectroscopy.
AB  - We propose a method for determining the time origin on the basis of causality in
      terahertz (THz) emission spectroscopy. The method is formulated in terms of the
      singly subtractive Kramers-Kronig relation, which is useful for the situation
      where not only the amplitude spectrum but also partial phase information is
      available within the measurement frequency range. Numerical analysis of several
      simulated and observed THz emission data shows that the misplacement of the time
      origin in THz waveforms can be detected by the method with an accuracy that is an
      order of magnitude higher than the given temporal resolutions.

PMID- 21716519
TI  - Active-mirror-laser-amplifier thermal management with tunable helium pressure at
      cryogenic temperatures.
AB  - We illustrate the benefits of a thin, low pressure helium cell for efficient and
      safe heat removal in cryogenically-cooled active mirror laser amplifiers
      operating in the [100 J-1 kJ]/[1-10 Hz] range. A homogeneous gain medium
      temperature distribution averaging 160 K is obtained with a sub-mm helium-filled
      gap between the gain medium and a copper plate at 77 K. A significant degree of
      flexibility for tuning the temperature in the amplifier can be achieved by
      varying the pressure of the helium gas in the 10(2) to 10(5) Pa range.

PMID- 21716520
TI  - Quality parameter for coherent transmissions with Gaussian-distributed nonlinear
      noise.
AB  - By assuming the nonlinear noise as a signal-independent circular gaussian noise,
      a typical case in non-dispersion managed links with coherent multilevel
      modulation formats, we provide several analytical properties of a new quality
      parameter--playing the role of the signal to noise ratio (SNR) at the sampling
      gate in the coherent receiver--which carry over to the Q-factor versus power (or
      "bell") curves. We show that the maximum Q is reached at an optimal power, the
      nonlinear threshold, at which the amplified spontaneous emission (ASE) noise
      power is twice the nonlinear noise power, and the SNR penalty with respect to
      linear propagation is 10Log(3/2) ? 1.76  dB,, although the Q-penalty is somewhat
      larger and increases at lower Q-factors, as we verify for the polarization
      division multiplexing quadrature phase shift keying (PDM-QPSK) format. As we vary
      the ASE power, the maxima of the SNR vs. power curves are shown to slide along a
      straight-line with slope ?-2 dB/dB. A similar behavior is followed by the Q
      factor maxima, although for PDM-QPSK the local slope is around -2.7 dB/dB for Q
      values of practical interest.

PMID- 21716521
TI  - Adaptive frequency-domain equalization in digital coherent optical receivers.
AB  - We propose a novel frequency-domain adaptive equalizer in digital coherent
      optical receivers, which can reduce computational complexity of the conventional
      time-domain adaptive equalizer based on finite-impulse-response (FIR) filters.
      The proposed equalizer can operate on the input sequence sampled by free-running
      analog-to-digital converters (ADCs) at the rate of two samples per symbol;
      therefore, the arbitrary initial sampling phase of ADCs can be adjusted so that
      the best symbol-spaced sequence is produced. The equalizer can also be configured
      in the butterfly structure, which enables demultiplexing of polarization
      tributaries apart from equalization of linear transmission impairments. The
      performance of the proposed equalization scheme is verified by 40-Gbits/s dual
      polarization quadrature phase-shift keying (QPSK) transmission experiments.

PMID- 21716522
TI  - Imitation of variable structural color in Paracheirodon innesi using colloidal
      crystal films.
AB  - Spacing variation of adjoining reflecting thin films in iridophore is responsible
      for the variable interference color in the paracheirodon innesi. On the basis of
      this phenomenon, colloidal crystal thin films with different structures are
      fabricated from monodisperse poly(styrene-methyl methacrylate-acrylic acid)
      (PSMA) colloids. The relationship between the colors and structures of the films
      is investigated and discussed according to the principle of light interference. A
      two-layer colloidal film having uniform color is researched and it displays
      diverse colors before and after swelling by styrene (St), which can be used to
      mimic the variable structural color of the paracheirodon innesi.

PMID- 21716523
TI  - Dynamic three-dimensional sensing for specular surface with monoscopic fringe
      reflectometry.
AB  - Dynamic full-field three-dimensional sensing of specular reflective surfaces can
      be conveniently implemented with fringe reflection technique. A monoscopic fringe
      reflectometric system can be adopted as a simple measuring setup. With the
      assistance of the windowed Fourier ridges method as an advanced fringe
      demodulation technique, only one cross grating is needed to reconstruct the three
      dimensional surface shape changes. A suitable calibration enables determination
      of the actual three-dimensional surface profile. Experimental results of water
      wave variations are shown to demonstrate the feasibility of the proposed
      approach.

PMID- 21716524
TI  - Matrix calculus for axially symmetric polarized beam.
AB  - The Jones calculus is a well known method for analyzing the polarization of a
      fully polarized beam. It deals with a beam having spatially homogeneous
      polarization. In recent years, axially symmetric polarized beams, where the
      polarization is not homogeneous in its cross section, have attracted great
      interest. In the present article, we show the formula for the rotation of beams
      and optical elements on the angularly variant term-added Jones calculus, which is
      required for analyzing axially symmetric beams. In addition, we introduce an
      extension of the Jones calculus: use of the polar coordinate basis. With this
      calculus, the representation of some angularly variant beams and optical elements
      are simplified and become intuitive. We show definitions, examples, and
      conversion formulas between different notations.

PMID- 21716525
TI  - Efficient frequency downconversion at the single photon level from the red
      spectral range to the telecommunications C-band.
AB  - We report on single photon frequency downconversion from the red part of the
      spectrum (738 nm) to the telecommunications C-band. By mixing attenuated laser
      pulses with an average photon number per pulse < 1 with a strong continuous light
      field at 1403 nm in a periodically poled Zn:LiNbO3 ridge waveguide an internal
      conversion efficiency of ~ 73% is achieved. We further investigate the noise
      properties of the process by measuring the output spectrum. Our results indicate
      that by narrow spectral filtering a quantum interface should be feasible which
      bridges the wavelength gap between quantum emitters like color centers in diamond
      emitting in the red part of the spectrum and low-loss fiber-optic
      telecommunications wavelengths.

PMID- 21716526
TI  - Optical magnetic response in three-dimensional metamaterial of upright plasmonic
      meta-molecules.
AB  - We report the first three-dimensional photonic metamaterial, an array of erected
      U-shape plasmonic gold meta-molecules, that exhibits a profound response to the
      magnetic field of light incident normal to the array. The metamaterial was
      fabricated using a double exposure e-beam lithographic process. It was
      investigated by optical measurements and finite-element simulations, and showed
      that the magnetic field solely depends on the plasmonic resonance mode showing
      either enhanced in the centre of the erected U-shape meta-molecule (16 times
      enhancement) or enhanced around two prongs of erected U-shape meta-molecule (4
      times enhancement).

PMID- 21716536
TI  - Retraction notice.

PMID- 21716527
TI  - Improvement of absorption and scattering discrimination by selection of sensitive
      points on temporal profile in diffuse optical tomography.
AB  - We present a new method allowing the reconstruction of 3D time-domain diffuse
      optical tomography images, based on the time-dependent diffusion equation and an
      iterative algorithm (ART) using specific points on the temporal profiles. The
      first advantage of our method versus the full time-resolved scheme consists in
      considerably reducing the inverse problem resolution time. Secondly, in the
      presence of scattering heterogeneities, our method provides images of better
      quality comparatively to classical methods using full-time data or the first
      moments of the profiles.

PMID- 21716537
TI  - Scoring systems in pemphigus.
AB  - Pemphigus is a dreaded disease encountered not infrequently in dermatology
      settings. While scoring systems in various dermatological conditions exist,
      objective parameters for assessing disease activity and therapeutic responses in
      pemphigus are not uniform and foolproof. This article presents various scoring
      systems in pemphigus.

PMID- 21716538
TI  - Acetylation phenotype variation in pediatric patients with atopic dermatitis.
AB  - BACKGROUND: Few studies have been done on the relation between acetylator status
      and allergic diseases. AIM: To determine any possible association between
      acetylating phenotype in pediatric patients with atopic dermatitis (AD) and the
      disease prognosis. PATIENTS AND METHODS: Thirty-six pediatric patients and forty
      two healthy children as a control group were participated in the study. All
      participants received a single oral dose of dapsone of 1.54 mg/kg body weight,
      after an overnight fast. Using high performance liquid chromatography (HPLC),
      plasma concentrations of dapsone and its metabolite (monoacetyldapsone) were
      estimated to phenotype the participants as slow and rapid acetylators according
      to their acetylation ratio (ratio of monoacetyldapsone to dapsone). RESULTS:
      72.2% of pediatric patients with AD showed slow acetylating status as compared to
      69.4% of control individuals. Also, 73% of AD patients with slow acetylating
      phenotype had familial history of allergy. The severity of AD occurred only in
      slow acetylator patients. The eczematous lesions in slow acetylators presented
      mainly in the limbs, while in rapid acetylators, they were found mostly in face
      and neck. CONCLUSION: This study shows an association between the N-acetylation
      phenotype variation and clinical aspects of AD.

PMID- 21716539
TI  - Linear IgA bullous dermatosis in tunisian children: 31 cases.
AB  - BACKGROUND: Linear IgA bullous dermatosis (LAD) of children is relatively
      frequent in Africa. AIM: We undertook this study to evaluate the frequency of
      this disease among autoimmune bullous diseases (AIBDs) in Tunisian children.
      MATERIALS AND METHODS: We present a 32-year retrospective study (January 1976 to
      December 2007). Children with chronic acquired bullous diseases seen at the
      Charles Nicolle Hospital of Tunis and for who direct immunofluorescence (DIF) of
      the perilesional skin demonstrated linear IgA immunoglobulin deposits were
      included in the study population. RESULTS: Thirty-one children with LAD were
      selected representing 65.9% of all AIBDs of children selected in the same period,
      with a mean age of 5.5 years and a sex ratio (M/F) of 2.4. Most of the children
      had generalized eruption (28/31), more profuse on the face, pelvic region,
      buttocks and limbs. Mucosal lesions happened in only four children (12.9%). The
      mean duration of the disease was 14 months. DIF demonstrated linear IgA deposits
      along the dermal-epidermal junction in all patients. IgG, IgM, and complement
      were also seen (20/31). Indirect immunofluorescence was negative in 67% of cases.
      Eight patients responded to dapsone; however, prednisone had to be added in seven
      children to control the disease and erythromycin in four others. A long-term
      remission period was achieved in 76.1% of patients. CONCLUSION: This study
      confirms that LAD is the most common AIBD in children in Tunisia which frequently
      occurs in preschool-aged males. Independently of the used drug, a long-term
      remission is frequently observed.

PMID- 21716540
TI  - Cutaneous disorders in 500 diabetic patients attending diabetic clinic.
AB  - BACKGROUND: The metabolic complications and pathologic changes that occur in
      diabetes mellitus (DM) influence the occurrence of various dermatoses. AIM: To
      study the impact of control of diabetes on the pattern of cutaneous disorders.
      MATERIALS AND METHODS: A cross-sectional descriptive study of patients attending
      diabetic clinic in a tertiary care hospital. A total of 500 consecutive patients
      were studied. Detailed history, clinical examination and relevant investigations
      were done to diagnose diabetic complications and cutaneous disorders. Dermatoses
      with or without known pathogenesis were correlated with age, gender, fasting
      plasma glucose (FPG), duration of diabetes, and complications of DM. Statistical
      analysis was carried out using Student "t" test and Chi-square test with 5%
      confidence interval (P value 0.05). RESULTS: Majority of patients had well
      controlled (FPG<130 mg/ml, 60%) type 2 DM (98.8%). No statistically significant
      difference (P>0.05) between the patients with or without DM specific cutaneous
      disorders was noticed with reference to age and gender distribution, duration of
      DM and FPG. Signs of insulin resistance, acrochordon (26.2%), and acanthosis
      nigricans (5%) were common, followed by fungal (13.8%) and bacterial (6.8%)
      infections. Eruptive xanthoma (0.6%), diabetic foot (0.2%), diabetic bulla
      (0.4%), diabetic dermopathy (0.2%), generalized granuloma annulare (0.2%), and
      insulin reactions (6.2%) and lipodystrophy (14%) were also seen. CONCLUSION: Well
      controlled diabetes decreases the prevalence of DM-specific cutaneous disorders
      associated with chronic hyperglycemia. It is necessary to have a dermatologist in
      the diabetic clinic for early detection of potentially grave or predisposing
      conditions.

PMID- 21716541
TI  - Comparative therapeutic evaluation of different topicals and narrow band
      ultraviolet B therapy combined with systemic methotrexate in the treatment of
      palmoplantar psoriasis.
AB  - BACKGROUND: The incidence of uncomplicated psoriasis is 1-3% in the general
      population. The involvement of palm and sole is seen in 7-14.5% of cases. There
      are different topicals and systemic therapies available for treating the case of
      psoriasis but none is satisfactory for longer duration. AIM: The study involved
      the comparative therapeutic evaluation of the different topical regimens and
      narrow band ultraviolet B (NB-UVB) therapy in combination with systemic
      methotrexate. MATERIALS AND METHODS: The study was held in out-patient department
      of Skin, VD and Leprosy of B.R.D. Medical College, Gorakhpur, from July 2007 to
      December 2008. The group included 98 new cases of palmoplantar psoriasis. These
      cases were divided into eight groups according to the eight regimens involved in
      the study. The severity of psoriasis was assessed by the ESIF (erythema, scaling,
      induration and fissuring) score. RESULTS: The study showed that all the regimens
      had significant response rates. The combination of NB-UVB with systemic
      methotrexate had maximum response rate (64.85+/-4.52%) that was statistically
      significant (paired "t" at 16d.f. = 33.329, P<0.001) with minimum number of
      recurrences after stopping the treatment. The combination of halobetasol ointment
      with systemic methotrexate also had significant response rate (paired "t" at
      19d.f. = 13.5183, P<0.001) but had maximum number of cases with recurrence (70%)
      after stopping the treatment. CONCLUSION: These results suggest that the
      combination of every regimen with systemic methotrexate resulted in an early and
      a good improvement in the quality of life of patients suffering from psoriasis.
      It also shows that NB-UVB in combination with systemic methotrexate is more
      efficacious and has minimum recurrence rate and side effects in the treatment of
      palmoplantar psoriasis.

PMID- 21716542
TI  - The comparison between trichloroacetic Acid 50% and co(2) laser in the treatment
      of cutaneous leishmaniasis scar.
AB  - BACKGROUND: The scars of the cutaneous leishmaniasis and psychological problems
      of this disease need different interventions for its correction. AIM: Our
      objective in this study was to compare the efficacy of 50% trichloroacetic acid
      (TCA) solution and CO(2) laser for treatment of the atrophic scars due to
      leishmaniasis. MATERIALS AND METHODS: This was a randomized clinical trial
      performed in 92 patients. Patients were randomized into two groups: the first
      group was treated with 50% TCA solution, once monthly and for a maximum of 5
      months, and the second group was treated with CO(2) laser which was performed for
      only one time. Patients were followed-up at 3 and 6 months after starting the
      treatment. The improvement of scar was graded by a 6-point scale using digital
      camera and the collected data were analyzed using SPSS software. RESULTS: In this
      study, 74 females and 18 males were enrolled. The improvement of scar was 48.13%
      in the TCA group and 44.87% in the CO(2) laser group. This difference was not
      statically significant (P = 0.55). There was also no significant difference
      regarding side effects between these two groups. CONCLUSION: The results of our
      study showed that efficacy of focal with 50% TCA solution is compared with CO(2)
      laser in treatment of leishmaniasis scar. Because of the low cost and simple
      application of TCA solution in comparison with CO(2) laser, we suggest use of
      this treatment for correction of leishmaniasis scar or the atrophic scars.

PMID- 21716543
TI  - Effects of low-frequency ultrasound on microcirculation in venous leg ulcers.
AB  - BACKGROUND: Therapeutic low-frequency ultrasound (US) has been used for many
      years to improve wound healing in chronic wounds like venous leg ulcers. No human
      data are available for the possible effects of single US applications on
      microcirculation and their frequency-dependency. AIMS: To investigated the role
      of therapeutic low-frequency US on microcirculation of venous leg ulcers in vivo.
      PATIENTS AND METHODS: This is a pilot study on an inpatient basis. We use a newly
      developed low-frequency continuous-wave US-equipment composed of a US transducer
      based on piezo-fiber composites that allow the change of frequency. In this
      study, we apply US of 34 kHz, 53.5 kHz, and 75 kHz respectively. Twelve patients
      with chronic venous leg ulcers are analyzed. As an adjunct to good ulcer care,
      therapeutic US is applied, non-contacting, once a day, in a subaqual position for
      10 minutes. Microcirculation is assessed in the ulcers adjacent to skin before US
      therapy, immediately after the treatment and 30 minutes later. We use a micro
      light guide spectrophotometer (O2C, LEA Medizintechnik GmbH, Gieiotaen, Germany)
      for calculation of blood flow velocity, hemoglobin oxygen saturation (SCO(2)) and
      relative hemoglobin concentration (rHb) in 2 and 8 mm depth. Contact-free
      remission spectroscopy (SkinREM3, Color Control Chemnitz GmbH, Chemnitz, Germany)
      allows contact free measurements in the VIS-NIR range of the spectrum (400 +/-
      1600 nm). RESULTS: It is seen that therapeutic US is well tolerated. One patient
      dropped out from a treatment series since he developed erysipelas responding to
      standard antibiotic. Effects were seen at 34 kHz only. The SO(2) values increased
      after single US application. The values for rHb were higher in the superficial
      layer of the wound bed (depth 2 mm) compared to deeper parts (8 mm depth). US
      treatment did not result in significant changes of rHb and blood cell velocity.
      The data obtained by remission spectroscopy disclose an increase of oxygenized
      hemoglobin. CONCLUSIONS: The major findings are that continuous-wave low
      frequency US of 34 kHz, but not, 53.5 kHz or 75 kHz, has a temporary stimulatory
      effect on microcirculation mainly due to an improved oxygenation. Further studies
      with treatment series are necessary.

PMID- 21716544
TI  - Vitiligo: a review of some facts lesser known about depigmentation.
AB  - Vitiligo is a disorder that causes the destruction of melanocytes. It has three
      important factors underlying this destruction. The depigmented skin has many
      aberrant functions such as a muted response to contact allergens, a phenomenon
      also seen in mice that depigment. The white skin of those with vitiligo does not
      form non-melanoma skin cancers although the white skin of albinos, which has a
      similar color as vitiligo, is highly susceptible to skin cancer.

PMID- 21716545
TI  - Lewandowsky and lutz dysplasia: report of two cases in a family.
AB  - Lewandowsky and Lutz dysplasia, also known as epidermodysplasia verruciformis
      (EV), is an inherited disorder in which there is widespread and persistent
      infection with human papilloma virus, defect in cell-mediated immunity and
      propensity for malignant transformation. Differential clinical and
      histopathologic evolutions of lesions in two cases of familial EV are compared
      and discussed in detail. Cases were followed up for 7 years. Detailed history,
      clinical features and investigations, including skin biopsy from different sites
      at different times, were examined. Generalized pityriasis versicolor like
      hypopigmented lesions in both the cases, together with variable pigmented nodular
      actinic keratosis like lesions on sun-exposed areas, were present. Multiple skin
      biopsies done from various sites on different occasions revealed features typical
      of EV along with lesions, i.e., actinic keratosis, Bowen's disease, basal and
      squamous cell carcinoma, in the elder sibling. However, skin biopsy of the other
      sibling showed features of EV and seborrheic keratosis only till date. This study
      reveals that the disease progression is variable among two individuals of the
      same family. Malignant lesions were seen only on sun-exposed areas and may be
      associated with other skin lesions or infections such as angiokeratoma of Fordyce
      and tinea cruris, as seen in this report.

PMID- 21716546
TI  - Alkaptonuria.
AB  - A case of alkaptonuria, a rare disorder with autosomal recessive inheritance, is
      reported here. The patient had palmar pigmentation in addition to the usual
      features of alkaptonuria.

PMID- 21716547
TI  - Multiple generalized xanthogranuloma in adult: case report and treatment.
AB  - Xanthogranuloma is a benign, asymptomatic, and self-healing disorder of non
      Langerhans cell histiocytosis, affecting mostly infants, children, and rarely
      adults. Diagnosis is easy in typical cases but become more complex in unusual
      forms. We report a case of a 28-year-old male patient who presented with multiple
      diffuse brown-to-yellowish papulonodular eruptions over extremities, ears, face,
      trunk, and extensors of joints with almost bilaterally symmetrical distribution
      for a period of one month. Histopathological examination of the skin biopsy
      specimen revealed features of xanthogranuloma. The patient was put on
      isotretinoin 20 mg once daily. Most of the lesions subsided or flattened within
      two months of isotretinoin therapy. This case is interesting because of the
      severity and atypical nature of the disease and also, the patient responded with
      isotretinoin therapy. But further study is required to observe the effectiveness
      of isotretinoin in xanthogranuloma.

PMID- 21716548
TI  - Pustulotic arthro-osteitis (sonozaki syndrome).
AB  - Pustulotic arthro-osteitis, first described by Sonozaki, is a relatively rare
      disorder. Its prevalence is however probably underestimated in dermatological
      literature. Early recognition of the signs can prevent misdiagnosis. We describe
      a Turkish patient who presented with palmoplantar pustulosis and involvement of
      the sternoclavicular joint and peripheral oligoarthritis.

PMID- 21716549
TI  - Maffucci'S syndrome associated with hyperparathyroidism.
AB  - Maffucci's syndrome is a rare, congenital, nonhereditary, mesodermal dysplastic
      disease characterized by venous malformations and benign cartilaginous tumors.
      The occurrence of endocrine tumors in Maffucci's syndrome is very rare. We report
      a case of Maffucci's syndrome associated with hyperparathyroidism and
      multinodular goiter.

PMID- 21716550
TI  - Acetaminophen-induced cellulitis-like fixed drug eruption.
AB  - Acetaminophen is a widely used analgesic drug. Its adverse reactions are rare but
      severe. An 89-year-old man developed an indurated edematous and erythematous
      plaque on his left arm 1 day after acetaminophen ingestion. Cellulitis was
      suspected and antibiotictherapy was started but there was no improvement of the
      rash; there was a spectacular extension of the lesion with occurrence of flaccid
      vesicles and blisters in the affected sites. The diagnosis of generalized-bullous
      fixed drug eruption induced by acetaminophen was considered especially with a
      reported history of a previous milder reaction occurring in the same site.
      Acetaminophen was withdrawn and the rash improved significantly. According to the
      Naranjo probability scale, the eruption experienced by the patient was probably
      due to acetaminophen. Clinicians should be aware of the ability of acetaminophen
      to induce fixed drug eruption that may clinically take several aspects and may be
      misdiagnosed.

PMID- 21716551
TI  - Scle-lp overlap syndrome.
AB  - A 35-year-old female presented with scaly annular and pigmented lesions all over
      the body of 2 years duration. Her clinical features, histopathology,
      immunofluorescence findings and positive ANA and anti-Ro antibodies were
      suggestive of subacute cutaneous lupus erythematosus-lichen planus. We report
      this case because of its clinical rarity.

PMID- 21716552
TI  - Circumscribed palmar or plantar hypokeratosis: report of an italian case.
AB  - Circumscribed palmar or plantar hypokeratosis is a rare benign epidermal
      malformation of the skin. Clinically it shows asymptomatic, well-circumscribed,
      and depressed erythema persisting for many years on the palms or soles. Its main
      histopathologic feature shows a characteristic epidermal depression with an
      abrupt decrement in the thickness of the stratum corneum, with a sharp stair
      between normal and involved skin. We describe a case of a 68-year-old woman who
      presented with an erythematous, asymptomatic, well-circumscribed, depressed
      patch, on the right thenar eminence which had been present for years.

PMID- 21716553
TI  - Leishmaniasis of the lip diagnosed by lymph node aspiration and treated with a
      combination of oral ketaconazole and intralesional sodium stibogluconate.
AB  - A 26-year-old male who presented to the dermatology OPD with complaints of a
      swelling on his lip of 6 months' duration was on examination found to have a
      solitary ulcerated nodule over the lip and an enlarged submental lymph node. Skin
      smear and biopsy from the lesion did not yield the diagnosis. Needle aspiration
      from the draining lymph node revealed the diagnostic Leishman-Donovan bodies. The
      patient responded to treatment with a combination of oral ketoconazole and
      intralesional sodium stibogluconate. We report this case because of both the
      unusual location of the lesion and the unusual method of diagnosis and treatment.

PMID- 21716554
TI  - Hyaline cell-rich chondroid syringoma of the finger.
AB  - A mixed tumor is a neoplasm that has microscopic features of both epithelial and
      mesenchymal differentiation. Such mixed tumors are known as pleomorphic adenomas
      in the salivary glands, and their cutaneous counterparts are called chondroid
      syringomas. These tumors commonly occur in the head and neck region of middle
      aged men. Hyaline cell-rich chondroid syringoma is a rare benign variant of
      chondroid syringoma composed of cells with eosinophilic hyaline cytoplasm and
      plasmacytoid features, the origin of which remains elusive. Although very few
      cases have been reported in literature, it is important to be aware of this
      entity so as to avoid misdiagnosis on histopathological examination. In this
      report we present a case of hyaline cell-rich chondroid syringoma occurring in
      the finger.

PMID- 21716555
TI  - Periungual Basal cell carcinoma: a case report with review of literature.
AB  - Basal cell carcinomas (BCCs) are considered to be uncommon around the nail plate.
      An indolent lesion of this region should arouse suspicion of potential malignancy
      and a skin biopsy should be undertaken without delay. Early diagnosis can enable
      the physician to render simpler nondestructive modalities of treatment. In this
      article, we describe such a case of longstanding BCC of this region mimicking a
      traumatic ulcer. The nature of the ailment was finally discovered on biopsy and
      the carcinoma was initially treated with topical Imiquimod.

PMID- 21716556
TI  - Malignant melanoma of scrotal skin.
AB  - Black/bluish discolored skin tumor without cuticular covering de novo from site
      of origin could be a diagnostic feature of melanomas.

PMID- 21716557
TI  - Epidermolysis bullosa acquisita with moderately severe Dysphagia due to
      esophageal strictures.
AB  - Epidermolysis bullosa acquisita (EBA) is a chronic, autoimmune condition
      involving the skin and mucous membranes. Symptomatic mucosal involvement is rare,
      but can impact on quality of life, due to esophageal strictures and dysphagia. We
      report a case involving a 60-year-old male presenting with bullous skin lesions
      on areas of friction on his hands, feet and mouth. Milia were visible on some
      healed areas. Biopsy showed a subepidermal vesicle. Direct immunofluorescence
      showed intense linear junctional IgG and C3 at the dermo-epidermal junction.
      Serological tests also supported the diagnosis of EBA. Screening tests for
      underlying malignancies were negative. Despite treatment with systemic steroids,
      the patient developed increasing dysphagia, requiring further investigation with
      esophagoscopy and a barium swallow. Confirmation of extensive esophageal
      stricturing prompted adjustment of medications including an increase in systemic
      steroids and addition of azathioprine. Currently, the patient's disease remains
      under control, with improvement in all his symptoms and return of anti-basement
      membrane antibody levels to normal, whilst he remains on azathioprine 150 mg
      daily and prednisolone 5 mg daily. This case highlights the fact that the
      treatment of a given patient with EBA depends on severity of disease and co
      morbid symptoms. Newer immunoglobulin and biological therapies have shown promise
      in treatment resistant disease. Considering that long-term immunosuppressants or
      biologicals will be required, potential side effects of the drugs should be
      considered. If further deterioration occurs in this patient, cyclosporin A or
      intravenous immunoglobulin (IV Ig) will be considered. Vigilance for associated
      co-morbidities, especially malignancies, should always be maintained.

PMID- 21716558
TI  - Mudi-chood: on the forearm.
AB  - Mudi-Chood is a strange dermatosis affecting the nape of the neck and upper back
      of young women in Kerala State of south India. It was first described by us in
      1972. Here we report one more such case recently seen by us.

PMID- 21716559
TI  - Facial nodule in a 34-year-old man.

PMID- 21716560
TI  - Use of methotrexate in recalcitrant eczema.

PMID- 21716561
TI  - Erythema ab igne of chest in a patient with pulmonary tuberculosis.

PMID- 21716562
TI  - Lupus miliaris disseminatus faciei with unusual distribution of lesions.

PMID- 21716563
TI  - Cutaneous metastases from gastric adenocarcinoma.

PMID- 21716564
TI  - Nickel contact dermatitis from hypodermic needles.

PMID- 21716565
TI  - Trend of sexually transmitted infections in hiv seropositive and seronegative
      males: a comparative study at a tertiary care hospital of north East India.

PMID- 21716566
TI  - Successful removal of kinked J-guide wire under fluoroscopic guidance during
      central venous catheterization -A case report-.
AB  - Guidewire-associated complications that occur during the process of central
      venous catheterization include its kinking, looping, knotting and breakage. The
      removal of a looped or knotted guidewire is problematic because it can cause
      vessel damage, major hemorrhage, or embolization of a fractured guidewire. We
      report a case of guidewire kinking and its successful removal under fluoroscopic
      guidance.

PMID- 21716567
TI  - Tongue bite in a patient with tracheostomy after prone position -A case report-.
AB  - A 22-year-old man underwent an operation for posterolateral fusion of the lumbar
      spine at L3-5. He was ventilated via a tracheostomy site in a prone position for
      210 minutes. Ventilator function and eyeballs were checked periodically. After
      changing his position to supine for the wake-up test, it was noticed that his
      tongue was self-inflicted and looked to be cut unless immediate decompression was
      applied. After several manual attempts to open the mouth failed, anesthesia depth
      was deepened with thiopental sodium and neuromuscular blocker to decompress and
      reposition the tongue into the intraoral cavity. Minimal teeth marks and scarring
      remained after seven months without any complications.

PMID- 21716568
TI  - Posterior reversible encephalopathy syndrome in an untreated hypertensive patient
      after spinal surgery under general anesthesia -A case report-.
AB  - Posterior reversible encephalopathy syndrome (PRES) is an unfamiliar term to
      anesthesiologists, and this is characterized by neurologic symptoms that include
      mental change, headache, seizure and visual disturbance and also abnormal
      neuroimaging finding. A 71-year-old female patient was operated on for posterior
      decompression and total laminectomy under general anesthesia for the spinal
      stenosis. After the operation, she developed generalized tonic-clonic seizure and
      a stuporous mentality in the recovery room. The magnetic resonance imaging (MRI)
      revealed swelling and increased signal intensity at the deep gray nuclei,
      cerebral cortex and cerebellum. After one week, she returned to an alert
      mentality and then she was diagnosed with PRES. She was discharged without any
      neurologic deficit on postoperative day 20. This report describes our experience
      with PRES after spinal surgery was performed under general anesthesia on a
      suspected untreated hypertensive patient.

PMID- 21716569
TI  - Bilateral tension pneumothorax caused by an abrupt increase in airway pressure
      during cervical spine surgery in the prone position -A case report-.
AB  - Elevated peak inspiratory airway pressure (PIP) can occur during general
      anesthesia and is usually easily rectified. In rare circumstances it can lead to
      potentially fatal conditions such as tension pneumothorax. We report on a 77-year
      old male patient admitted for a cervical laminoplasty. The preoperative chest
      radiograph showed normal findings and there was no medical history of allergy or
      underlying airway inflammation. Anesthesia induction and maintenance progressed
      uneventfully. However, 5 minutes after prophylactic antibiotic administration,
      PIP suddenly increased and blood pressure dropped. The operation was abandoned
      and the patient was moved to a supine position to perform chest radiography.
      Cardiac arrest occurred, and cardiopulmonary resuscitation was performed. The
      radiograph showed bilateral tension pneumothorax. Needle aspiration was
      immediately performed, and chest tubes were inserted. Ventilation rapidly
      improved and the vital signs normalized. The patient was discharged without
      sequelae on postoperative day 36.

PMID- 21716570
TI  - Postoperative obstructing laryngeal edema in patients with diffuse idiopathic
      skeletal hyperostosis of cervical spine -A report of two cases-.
AB  - Two cases were reported in which severe postoperative laryngeal edema were
      developed after the operation of diffuse idiopathic skeletal hyperostosis (DISH)
      of cervical spine. In the first case, sudden airway obstruction was developed in
      the general ward 6 hour after uneventful decompression surgery for osteophyte. In
      the second patient, an elective preoperative tracheostomy was performed before
      surgery but the tube could not be removed for 2 months because of laryngeal edema
      and decreased vocal cord mobility. It should be emphasized that this airway
      problem can develop during the postoperative as well as the preoperative period,
      especially in the case of anterior cervical spine surgery.

PMID- 21716571
TI  - Combined rigid videolaryngoscopy-flexible bronchoscopy for intubation.

PMID- 21716572
TI  - Techniques for microsurgical reconstruction of obstructive azoospermia.
AB  - About 10%-15% of infertile men present with azoospermia, and ductal obstruction
      is the cause in 40% of them. For about 25-30 years, microsurgical reconstruction
      was the only way to manage obstructive azoospermia, and several innovative
      techniques have been developed and implemented. Presently, assisted reproductive
      technologies (ART) are available for these men as an alternative to surgery.
      Clinicians who treat these men must be familiar with all of these options, and
      many of the ART techniques have been covered in other sections of this symposium.
      However, the present article focuses on vasovasostomies and vasoepididymostomies.
      The intent of this review is to critique these microsurgical procedures, and
      present some surgical "pearls" related to them.

PMID- 21716573
TI  - The question of "representation" in the psychoanalytical and cognitive-behavioral
      approaches. Some theoretical aspects and therapy considerations.
AB  - This paper compares the cognitive-behavioral and psychoanalytical approaches with
      respect to the way in which each of them conceives of representation and deals
      with the issues that this involves. In both of them conscious and latent
      (unconscious) representations play a crucial role. Highlighting similarities and
      differences facilitate communication on a theoretical level but also prove
      helpful to the clinical practitioners involved. We try to put forward an attempt
      at comparison, with the idea of going beyond the - obviously important -
      differences in vocabulary. In this attempt at comparison, we have successively
      compared the definitions of representation and the respective therapeutic
      interventions proposed by each approach. There are no doubt many overlapping
      elements in the way in which the workings of the mind are conceived of in these
      approaches, particularly as regards their links with affects. We next developed
      the implications of representation deficits in pathology, suggesting the
      important role played by elements that are avoided, suppressed from memory or
      repressed, and with respect to the need to treat such material in a specific
      manner so as to ensure some progress as to the symptoms presented. We finally
      summarized common and distinct aspects of the two perspectives. The very fact
      that two approaches that follow very distinct methodologies reach the same
      conclusion concerning the importance of distortions and failures of
      representation in generating mental distress strengthens, in our view, the
      epistemological reliability of the role of representation in psychopathology.

PMID- 21716574
TI  - Acoustic processing of temporally modulated sounds in infants: evidence from a
      combined near-infrared spectroscopy and EEG study.
AB  - Speech perception requires rapid extraction of the linguistic content from the
      acoustic signal. The ability to efficiently process rapid changes in auditory
      information is important for decoding speech and thereby crucial during language
      acquisition. Investigating functional networks of speech perception in infancy
      might elucidate neuronal ensembles supporting perceptual abilities that gate
      language acquisition. Interhemispheric specializations for language have been
      demonstrated in infants. How these asymmetries are shaped by basic temporal
      acoustic properties is under debate. We recently provided evidence that newborns
      process non-linguistic sounds sharing temporal features with language in a
      differential and lateralized fashion. The present study used the same material
      while measuring brain responses of 6 and 3 month old infants using simultaneous
      recordings of electroencephalography (EEG) and near-infrared spectroscopy (NIRS).
      NIRS reveals that the lateralization observed in newborns remains constant over
      the first months of life. While fast acoustic modulations elicit bilateral
      neuronal activations, slow modulations lead to right-lateralized responses.
      Additionally, auditory-evoked potentials and oscillatory EEG responses show
      differential responses for fast and slow modulations indicating a sensitivity for
      temporal acoustic variations. Oscillatory responses reveal an effect of
      development, that is, 6 but not 3 month old infants show stronger theta-band
      desynchronization for slowly modulated sounds. Whether this developmental effect
      is due to increasing fine-grained perception for spectrotemporal sounds in
      general remains speculative. Our findings support the notion that a more general
      specialization for acoustic properties can be considered the basis for
      lateralization of speech perception. The results show that concurrent assessment
      of vascular based imaging and electrophysiological responses have great potential
      in the research on language acquisition.

PMID- 21716575
TI  - Monkeys (macaca mulatta and cebus apella) and human adults and children (homo
      sapiens) compare subsets of moving stimuli based on numerosity.
AB  - Two monkey species (Macaca mulatta and Cebus apella) and human children and
      adults judged the numerousness of two subsets of moving stimuli on a computer
      screen. Two sets of colored dots that varied in number and size were intermixed
      in an array in which all dots moved in random directions and speeds. Participants
      had to indicate which dot color was more numerous within the array. All species
      performed at high and comparable levels, including on trials in which the subset
      with the larger number of items had a smaller total area of coloration. This
      indicated a similarity across species to use the number of items in the subsets,
      and not dimensions such as area or volume, to guide decision making.
      Discrimination performance was constrained by the ratio between the subsets,
      consistent with other reports of numerousness judgments of stationary stimuli.
      These results indicate a similarity in numerical estimation ability for moving
      stimuli across primate species, and this capacity may be necessary for naturally
      occurring experiences in which moving stimuli must be summed.

PMID- 21716576
TI  - Task-irrelevant blindsight and the impact of invisible stimuli.
AB  - Despite their subjective invisibility, stimuli presented within regions of
      absolute cortical blindness can both guide forced-choice behavior when they are
      task-relevant and modulate responses to visible targets when they are task
      irrelevant. We here tested three hemianopic patients to learn whether their
      performance in an attention-demanding rapid serial visual presentation task would
      be affected by task-irrelevant stimuli. Per trial, nine black letters and one
      white target letter appeared briefly at fixation; the white letter was to be
      named at the end of each trial. On 50% of trials, a task-irrelevant disk (-0.6
      log contrast) was presented to the blind field; in separate blocks, the same or a
      very low negative contrast distractor was presented to the sighted field. Mean
      error rates were high and independent of distractor condition, although the high
      contrast sighted-field disk impaired performance significantly in one
      participant. However, when trials with and without distractors were considered
      separately, performance was most impaired by the high-contrast disk in the blind
      field, whereas the same disk in the sighted field had no effect. As this disk was
      least visible in the blind and most visible in the sighted field, attentional
      suppression was inversely related to visibility. We suggest that visual
      awareness, or the processes that generate it and are compromised in the blind
      hemisphere, enhances or enables effective attentional suppression.

PMID- 21716578
TI  - The cultural constitution of cognition: taking the anthropological perspective.
AB  - To what extent is cognition affected by culture? And how might cognitive science
      profit from an intensified collaboration with anthropology in exploring this
      issue? In order to answer these questions, we will first give a brief description
      of different perspectives on cognition, one that prevails in most cognitive
      sciences - particularly in cognitive psychology - and one in anthropology. Three
      basic assumptions of cognitive science regarding the separability of content and
      process, the context-independence of processing, and the culture-independence of
      processing will then be discussed. We argue that these assumptions need to be
      questioned and scrutinized cross-culturally. A thorough examination of these
      issues would profit considerably from collaboration with anthropologists, not
      only by enabling deeper insight into the cultures under scrutiny, but also by
      synergistic effects that would allow for a more comprehensive understanding of
      human cognition.

PMID- 21716577
TI  - A dual-route approach to orthographic processing.
AB  - In the present theoretical note we examine how different learning constraints,
      thought to be involved in optimizing the mapping of print to meaning during
      reading acquisition, might shape the nature of the orthographic code involved in
      skilled reading. On the one hand, optimization is hypothesized to involve
      selecting combinations of letters that are the most informative with respect to
      word identity (diagnosticity constraint), and on the other hand to involve the
      detection of letter combinations that correspond to pre-existing sublexical
      phonological and morphological representations (chunking constraint). These two
      constraints give rise to two different kinds of prelexical orthographic code, a
      coarse-grained and a fine-grained code, associated with the two routes of a dual
      route architecture. Processing along the coarse-grained route optimizes fast
      access to semantics by using minimal subsets of letters that maximize information
      with respect to word identity, while coding for approximate within-word letter
      position independently of letter contiguity. Processing along the fined-grained
      route, on the other hand, is sensitive to the precise ordering of letters, as
      well as to position with respect to word beginnings and endings. This enables the
      chunking of frequently co-occurring contiguous letter combinations that form
      relevant units for morpho-orthographic processing (prefixes and suffixes) and for
      the sublexical translation of print to sound (multi-letter graphemes).

PMID- 21716579
TI  - Affordances, adaptive tool use and grounded cognition.

PMID- 21716580
TI  - Ongoing EEG Phase as a Trial-by-Trial Predictor of Perceptual and Attentional
      Variability.
AB  - Even in well-controlled laboratory environments, apparently identical repetitions
      of an experimental trial can give rise to highly variable perceptual outcomes and
      behavioral responses. This variability is generally discarded as a reflection of
      intrinsic noise in neuronal systems. However, part of this variability may be
      accounted for by trial-by-trial fluctuations of the phase of ongoing oscillations
      at the moment of stimulus presentation. For example, the phase of an electro
      encephalogram (EEG) oscillation reflecting the rapid waxing and waning of
      sustained attention can predict the perception of a subsequent visual stimulus at
      threshold. Similar ongoing periodicities account for a portion of the trial-by
      trial variability of visual reaction times. We review the available experimental
      evidence linking ongoing EEG phase to perceptual and attentional variability, and
      the corresponding methodology. We propose future tests of this relation, and
      discuss the theoretical implications for understanding the neuronal dynamics of
      sensory perception.

PMID- 21716581
TI  - Effects of Music Listening on Cortisol Levels and Propofol Consumption during
      Spinal Anesthesia.
AB  - BACKGROUND: This study explores effects of instrumental music on the hormonal
      system (as indicated by serum cortisol and adrenocorticotropic hormone), the
      immune system (as indicated by immunoglobulin A) and sedative drug requirements
      during surgery (elective total hip joint replacement under spinal anesthesia with
      light sedation). This is the first study investigating this issue with a double
      blind design using instrumental music. METHODOLOGY/PRINCIPAL FINDINGS: Patients
      (n = 40) were randomly assigned either to a music group (listening to
      instrumental music), or to a control group (listening to a non-musical placebo
      stimulus). Both groups listened to the auditory stimulus about 2 h before, and
      during the entire intra-operative period (during the intra-operative light
      sedation, subjects were able to respond lethargically to verbal commands).
      Results indicate that, during surgery, patients of the music group had a lower
      propofol consumption, and lower cortisol levels, compared to the control group.
      CONCLUSION/SIGNIFICANCE: Our data show that listening to music during surgery
      under regional anesthesia has effects on cortisol levels (reflecting stress
      reducing effects) and reduces sedative requirements to reach light sedation.

PMID- 21716582
TI  - Manipulating objects and telling words: a study on concrete and abstract words
      acquisition.
AB  - Four experiments (E1-E2-E3-E4) investigated whether different acquisition
      modalities lead to the emergence of differences typically found between concrete
      and abstract words, as argued by the words as tools (WAT) proposal. To mimic the
      acquisition of concrete and abstract concepts, participants either manipulated
      novel objects or observed groups of objects interacting in novel ways (Training
      1). In TEST 1 participants decided whether two elements belonged to the same
      category. Later they read the category labels (Training 2); labels could be
      accompanied by an explanation of their meaning. Then participants observed
      previously seen exemplars and other elements, and were asked which of them could
      be named with a given label (TEST 2). Across the experiments, it was more
      difficult to form abstract than concrete categories (TEST 1); even when adding
      labels, abstract words remained more difficult than concrete words (TEST 2). TEST
      3 differed across the experiments. In E1 participants performed a feature
      production task. Crucially, the associations produced with the novel words
      reflected the pattern evoked by existing concrete and abstract words, as the
      first evoked more perceptual properties. In E2-E3-E4, TEST 3 consisted of a color
      verification task with manual/verbal (keyboard-microphone) responses. Results
      showed the microphone use to have an advantage over keyboard use for abstract
      words, especially in the explanation condition. This supports WAT: due to their
      acquisition modality, concrete words evoke more manual information; abstract
      words elicit more verbal information. This advantage was not present when
      linguistic information contrasted with perceptual one. Implications for theories
      and computational models of language grounding are discussed.

PMID- 21716583
TI  - The coding and inter-manual transfer of movement sequences.
AB  - The manuscript reviews recent experiments that use inter-manual transfer and
      inter-manual practice paradigms to determine the coordinate system (visual
      spatial or motor) used in the coding of movement sequences during physical and
      observational practice. The results indicated that multi-element movement
      sequences are more effectively coded in visual-spatial coordinates even following
      extended practice, while very early in practice movement sequences with only a
      few movement elements and relatively short durations are coded in motor
      coordinates. Likewise, inter-manual practice of relatively simple movement
      sequences show benefits of right and left limb practice that involves the same
      motor coordinates while the opposite is true for more complex sequences. The
      results suggest that the coordinate system used to code the sequence information
      is linked to both the task characteristics and the control processes used to
      produce the sequence. These findings have the potential to greatly enhance our
      understanding of why in some conditions participants following practice with one
      limb or observation of one limb practice can effectively perform the task with
      the contralateral limb while in other (often similar) conditions cannot.

PMID- 21716584
TI  - What Phonological Facilitation Tells about Semantic Interference: A Dual-Task
      Study.
AB  - Despite increasing interest in the topic, the extent to which linguistic
      processing demands attentional resources remains poorly understood. We report an
      empirical re-examination of claims about lexical processing made on the basis of
      the picture-word interference task when merged in a dual-task psychological
      refractory period (PRP) paradigm. Two experiments were conducted in which
      participants were presented with a tone followed, at varying stimulus onset
      asynchronies (SOAs), by a picture-word stimulus. In Experiment 1, the
      phonological relatedness between pictures and words was manipulated. Begin- and
      end-related words decreased picture naming latencies relative to unrelated words.
      This effect was additive with SOA effects. In Experiment 2, both the semantic and
      the phonological relatedness between pictures and words were manipulated.
      Replicating Experiment 1, effects arising from the phonological manipulation were
      additive with SOA effects on picture naming latencies. In contrast, effects
      arising from the semantic manipulation were under additive with SOA effects on
      picture naming latencies, that is, semantic interference decreased as SOA was
      decreased. Such contrastive pattern suggests that semantic and phonological
      effects on picture naming latencies are characterized by distinguishable sources,
      the former prior to the PRP bottleneck and the latter at the PRP bottleneck or
      after. The present findings are discussed in relation to current models of
      language production.

PMID- 21716585
TI  - Klotho and the aging process.
AB  - The klotho gene was originally identified as a putative age-suppressing gene in
      mice that extends life span when overexpressed. It induces complex phenotypes
      resembling human premature aging syndromes when disrupted. The gene was named
      after a Greek goddess Klotho who spun the thread of life. Since then, various
      functional aspects of the klotho gene have been investigated, leading to the
      identification of multiple novel endocrine axes that regulate various metabolic
      processes and an unexpected link between mineral metabolism and aging. The
      purposes of this review were to overview recent progress on Klotho research and
      to discuss a novel aging mechanism.

PMID- 21716586
TI  - Current status of dialysis therapy in Korea.
AB  - The number of patients with end-stage renal disease (ESRD) is rising very rapidly
      as the number of elderly and patients with diabetes increases in Korea. ESRD
      Registry Committee of the Korean Society of Nephrology (KSN) collected dialysis
      therapy data in Korea through an online registry program on the KSN website. The
      status of renal replacement therapy in Korea at the end of 2009 was as follows.
      First, total number of patients with ESRD was 56,396 (hemodialysis [HD], 37,391;
      peritoneal dialysis [PD], 7,618; functioning kidney transplant [KT], 11,387). The
      prevalence of ESRD was 1,113.6 patients per million population (PMP). Proportion
      of patients undergoing renal replacement therapy was 66.3% with HD, 13.5% with
      PD, and 20.2% with KT. Second, a total of 8,906 (HD, 6,540; PD, 1,125; KT, 1,241;
      incidence rate of 175.9 PMP) patients developed ESRD in 2009. Third, the most
      common primary causes of ESRD were diabetic nephropathy (45.4%), hypertensive
      nephrosclerosis (18.3%), and chronic glomerulonephritis (11.1%). Fourth, mean
      urea reduction rate was 67.5% and 73.8% in male and female patients,
      respectively, undergoing HD. Mean Kt/V was 1.38 in male patients and 1.65 in
      female patients. Fifth, the overall 5-year survival rate of male patients
      undergoing dialysis was 65.4% and that of female patients was 67.4%.

PMID- 21716587
TI  - The endoscopic cryotherapy of lung and bronchial tumors: a systematic review -can
      we expect a new era of cryotherapy in lung cancer?

PMID- 21716588
TI  - Tool for guidance: evidence-based recommendations for managing febrile
      neutropenia.

PMID- 21716589
TI  - Endoscopic cryotherapy of lung and bronchial tumors: a systematic review.
AB  - BACKGROUND/AIMS: We made a systematic review and evaluation of endoscopic
      cryotherapy of endobronchial tumors, investigating safety and efficacy. METHODS:
      Qualified studies regarding endoscopic cryotherapy of lung tumors were
      systemically evaluated using available databases according to predefined
      criteria. RESULTS: In total, 16 publications were included in the final
      assessment. A narrative synthesis was performed because a formal meta-analysis
      was not viable due to the lack of controlled studies and study heterogeneity.
      Overall success rates for significant recanalization of the obstruction were
      approximately 80%, although they varied, depending on disease status in the
      patient population. Complications from the procedure developed in 0-11.1% of
      cases, most of which were minor and controlled by conservative management.
      Although limited data were available on comprehensive functional assessment, some
      studies showed that respiratory symptoms, pulmonary function tests, and
      performance status were significantly improved. CONCLUSIONS: Endoscopic
      cryotherapy was found to be a safe and useful procedure in the management of
      endobronchial tumors although its efficacy and appropriate indications have yet
      to be determined in well-designed controlled studies.

PMID- 21716590
TI  - Detection of clopidogrel hyporesponsiveness using a point-of-care assay and the
      impact of additional cilostazol administration after coronary stent implantation
      in diabetic patients.
AB  - BACKGROUND/AIMS: Impaired responsiveness to clopidogrel is common in patients
      with type 2 diabetes mellitus (DM). The aim of this study was to evaluate the
      clinical application of a point-of-care assay to detect impaired responsiveness
      to clopidogrel after coronary stent implantation in patients with type 2 DM.
      METHODS: We measured P2Y12 reaction units (PRU) with the VerifyNow point-of-care
      assay in 544 consecutive patients undergoing dual or triple (i.e., dual plus
      cilostazol) anti-platelet therapy after coronary stent implantation. High
      platelet reactivity (HPR) was defined as a PRU value >= 240. RESULTS: The mean
      PRU values were 233.5 +/- 83.2 and 190.3 +/- 85.5 in patients undergoing dual or
      triple anti-platelet therapy, respectively (p < 0.001). Patients with DM
      manifested higher post treatment PRU values (238.3 +/- 82.4 vs. 210.8 +/- 86.8, p
      = 0.001) and a higher frequency of HPR (44.8% vs. 31.0%, p = 0.003) as compared
      to patients without DM. We also found that higher PRU values and a higher
      frequency of HPR were present in patients with DM who were undergoing both triple
      and dual anti-platelet therapy. However, the higher post-treatment PRU values
      observed in patients with DM decreased with triple anti-platelet therapy (219.4
      +/- 82.5 vs. 247.9 +/- 81.1, p = 0.044). CONCLUSIONS: A point-of-care assay can
      detect elevated platelet reactivity and impaired responsiveness to clopidogrel in
      patients with type 2 DM. The addition of cilostazol to dual anti-platelet therapy
      may decrease post-treatment PRU values in patients with type 2 DM.

PMID- 21716591
TI  - Retrospective comparison of levofloxacin and moxifloxacin on multidrug-resistant
      tuberculosis treatment outcomes.
AB  - BACKGROUND/AIMS: To compare the effect of levofloxacin and moxifloxacin on
      treatment outcomes among patients with multidrug-resistant tuberculosis (MDR-TB).
      METHODS: A retrospective analysis of 171 patients with MDR-TB receiving either
      levofloxacin or moxifloxacin was performed. Treatment responses were categorized
      into treatment success (cured and treatment completed) or adverse treatment
      outcome (death, failure, and relapsed). RESULTS: The median age of the patients
      was 42.0 years. Approximately 56% of the patients were male. Seventeen patients
      had extensively drug-resistant tuberculosis, and 20 had a surgical resection. A
      total of 123 patients (71.9%) received levofloxacin for a median 594 days, and 48
      patients (28.1%) received moxifloxacin for a median 673 days. Other baseline
      demographic, clinical, and radiographic characteristics were similar between the
      two groups. The moxifloxacin group had a significantly higher number of resistant
      drugs (p < 0.001) and a higher incidence of resistance to ofloxacin (p = 0.005)
      in the drug sensitivity test. The treatment success rate was 78.9% in the
      levofloxacin group and 83.3% in the moxifloxacin group (p = 0.42). Adverse
      reactions occurred at similar rates in the groups (p = 0.44). Patients in the
      moxifloxacin group were not more likely to have treatment success than those in
      the levofloxacin group (adjusted odds ratio, 0.76; 95% confidence interval, 0.24
      to 2.43; p = 0.65). CONCLUSIONS: Both levofloxacin and moxifloxacin showed
      equivalent efficacy for treating MDR-TB.

PMID- 21716592
TI  - Outcome of pandemic H1N1 pneumonia: clinical and radiological findings for
      severity assessment.
AB  - BACKGROUND/AIMS: Pandemic influenza A (H1N1) virus infection presents with
      variable severity. However, little is known about clinical predictors of disease
      severity. We studied the clinical predictors of severe pandemic H1N1 pneumonia
      and their correlation with radiological findings. METHODS: We reviewed medical
      and radiological records of adults with pandemic H1N1 pneumonia. After
      classification of patients into severe and non-severe groups, the following data
      were evaluated: demographic data, pneumonia severity index (PSI), CURB65, risk
      factors, time to first dose of antiviral medication, routine laboratory data,
      clinical outcome, and radiological characteristics. RESULTS: Of 37 patients with
      pandemic H1N1 pneumonia, 12 and 25 were assigned to the severe and non-severe
      groups, respectively. PSI score, serum aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and lactate dyhydrogenase (LDH) levels were higher in the
      severe group than in the non-severe group (p = 0.035, 0.0003, 0.0023, and 0.0002,
      respectively). AST, ALT, and LDH levels were positively correlated with the
      radiological findings (p < 0.0001, 0.0003, and < 0.0001, respectively) and with
      the number of involved lobes (p = 0.663, 0.0134, and 0.0019, respectively). The
      most common finding on high resolution computed tomography (HRCT) scans was
      ground-glass attenuation with consolidation (n = 22, 60%), which had a
      predominantly patchy distribution (n = 31). CONCLUSIONS: We demonstrated a
      positive correlation between clinical findings, such as serum AST, ALT, and LDH
      levels, and radiological findings. A combination of clinical and HRCT indicators
      would be useful in predicting the clinical outcome of pandemic H1N1 pneumonia.

PMID- 21716593
TI  - Effects of D-003 (10 mg/day) on bone mineral density of the lumbar spine and
      femoral neck in postmenopausal women: a randomized, double-blinded study.
AB  - BACKGROUND/AIMS: Increased osteoclast activity is a pivotal finding in
      osteoporosis. This increase is mediated via the mevalonate-to-cholesterol
      pathway, which is involved in producing the intermediates required for osteoclast
      activity. D-003, a mixture of high molecular weight sugarcane wax acids, has been
      shown to inhibit cholesterol synthesis prior to mevalonate production, resulting
      in a reduction of bone loss and resorption in ovariectomized rats. Moreover,
      previous studies have demonstrated that short-term D-003 treatment reduces
      urinary excretion of deoxypyridinoline/creatinine in postmenopausal women.
      METHODS: We performed a double-blinded, placebo-controlled study to investigate
      the effects of D-003 (10 mg/day) treatment for 3 years on bone mineral density
      (BMD) in 83 postmenopausal women with low BMD. RESULTS: Over 3 years, D-003
      treatment increased lumbar spine BMD (5.1%, p < 0.01) and improved osteoporosis
      related quality of life scores as compared with placebo-treated controls. D-003
      was also well tolerated; the frequency of adverse events in the bone, joints, or
      muscle with D-003 treatment (p < 0.05) was lower than in the placebo group.
      CONCLUSIONS: D-003 treatment (10 mg/day) for 3 years increased lumbar spine BMD
      and produced clinical improvements in postmenopausal women with low BMD. Further
      studies, however, will be required to confirm these results.

PMID- 21716594
TI  - Diagnostic value of a chimeric TSH receptor (Mc4)-based bioassay for Graves'
      disease.
AB  - BACKGROUND/AIMS: Graves' disease (GD) is caused by thyroid-stimulating hormone
      receptor (TSHR) and thyroid-stimulating immunoglobulin (TSI). We used a recently
      introduced, technically enhanced TSI bioassay to assess its diagnostic value and
      determine the cut-off in patients in high iodine intake area. METHODS: In a cross
      sectional setting, we collected serum from 67 patients with untreated GD, 130
      with GD under treatment, 22 with GD in remission, 42 with Hashimoto's
      thyroiditis, 12 with subacute thyroiditis, 20 with postpartum thyroiditis, and 93
      euthyroid controls. TSI was measured using the ThyretainTM bioassay, which is
      based on Chinese hamster ovary cells transfected with chimeric TSHR (Mc4). TSI
      levels are reported as a specimen-to-reference ratio percentage (SRR%). RESULTS:
      The TSI levels in patients with GD (either treated or not) were significantly
      higher than those of the remaining patients (p < 0.05). The new bioassay showed a
      sensitivity of 97.0% and a specificity of 95.9% with a cut-off value of 123.0
      SRR% for GD. A weak correlation was found between TSI and thyrotropin-binding
      inhibiting immunoglobulin (TBII) (r(s) = 0.259, p = 0.03), but no correlation was
      found between TSI and tri-iodothyronine or free thyroxine. CONCLUSIONS: The Mc4
      CHO bioassay showed comparable diagnostic value for GD with the conventional TBII
      assay. We propose a cut-off of 123.0 SRR% in areas where iodine intake is high.

PMID- 21716596
TI  - Reaching people through medical humanities: An initiative.

PMID- 21716595
TI  - Role of IL-1alpha in cisplatin-induced acute renal failure in mice.
AB  - BACKGROUND/AIMS: For unknown reasons, caspase-1 -/- mice, protected against
      cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)
      1alpha. We thus asked whether IL-1alpha deficiency underlies the mechanism of
      protection against cisplatin-induced ARF in these mice. METHODS: Cisplatin (30
      mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a
      cisplatin-induced model of ARF. IL-1alpha was measured in control vehicle- and
      cisplatin-treated wild-type animals. We also examined whether IL-1alpha -/- mice
      were similarly protected against cisplatin-induced ARF. Additionally,
      infiltration of CD11b- and CD49b-positive cells, as markers of macrophages,
      natural killer, and natural killer T cells (pan-NK cells), was investigated in
      wild-type and IL-1alpha -/- mice. RESULTS: Compared with vehicle-treated mice,
      renal IL-1alpha increased in cisplatin-treated wild-type mice beginning on day 1.
      IL-1alpha -/- mice were shown to be protected against cisplatin-induced ARF. No
      significant difference in the infiltration of neutrophils or CD11b- and CD49b
      positive cells were observed between wild-type and IL-1alpha -/- mice.
      CONCLUSIONS: Mice deficient in IL-1alpha are protected against cisplatin-induced
      ARF. The lack of IL-1alpha may explain, at least in part, the protection against
      cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the
      protective mechanism (s) in IL-1alpha -/- mice in cisplatin-induced ARF merits
      further study.

PMID- 21716597
TI  - Differential effect of contrast polarity reversals in closed squares and open L
      junctions.
AB  - Scene segmentation depends on interaction between geometrical and photometric
      factors. It has been shown that reversals in contrast polarity at points of
      highest orientation discontinuity along closed contours significantly impair
      shape discrimination performance, while changes in contrast polarity at
      straight(er) contour segments do not have such deleterious effects (Spehar,
      2002). Here we employ (semi) high resolution fMRI (1.5 mm * 1.5 mm * 1.5 mm) to
      investigate the neuronal substrate underlying these perception effects. Stimuli
      consisted of simple elements (a) squares with contrast reversals along straight
      segments; (b) squares with contrast reversals in the corner (highest orientation
      discontinuity); (c) L-Junctions with contrast reversals along the straight ends;
      (d) L-Junctions with contrast reversals in the corner. Element with contrast
      polarity reversals are easy to distinguish though appear geometrically
      equivalent. For squares with contrast polarity reversals only along straight
      lines we find significantly lower BOLD modulation compared to any of the control
      conditions, which show similar responses to each other. In the light of previous
      psychophysical work (Elder and Zucker, 1993; Spehar, 2002) we speculate that this
      effect is due to closure perception. We observe this across a wide range of areas
      on occipital cortex.

PMID- 21716598
TI  - Quality of Cohort Studies Reporting Post the Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) Statement.
AB  - The quality of reporting of cohort studies published in the most prestigious
      scientific medical journals was investigated to indicate to what extent the items
      in the Strengthening the Reporting of Observational Studies in Epidemiology
      (STROBE) checklist are addressed. Six top scientific medical journals with high
      impact factor were selected including New England Journal of Medicine, Journal of
      the American Medical Association, Lancet, British Medical Journal, Archive of
      Internal Medicine, and Canadian Medical Association Journal. Ten cohort studies
      published in 2010 were selected randomly from each journal. The percentage of
      items in the STROBE checklist that were addressed in each study was investigated.
      The total percentage of items addressed by these studies was 69.3 (95% confidence
      interval: 59.6 to 79.0). We concluded that reporting of cohort studies published
      in the most prestigious scientific medical journals is not clear enough yet. The
      reporting of other types of observational studies such as case-control and cross
      sectional studies particularly those being published in less prestigious journals
      expected to be much more imprecise.

PMID- 21716599
TI  - Trajectory recognition as the basis for object individuation: a functional model
      of object file instantiation and object-token encoding.
AB  - The perception of persisting visual objects is mediated by transient intermediate
      representations, object files, that are instantiated in response to some, but not
      all, visual trajectories. The standard object file concept does not, however,
      provide a mechanism sufficient to account for all experimental data on visual
      object persistence, object tracking, and the ability to perceive spatially
      disconnected stimuli as continuously existing objects. Based on relevant
      anatomical, functional, and developmental data, a functional model is constructed
      that bases visual object individuation on the recognition of temporal sequences
      of apparent center-of-mass positions that are specifically identified as
      trajectories by dedicated "trajectory recognition networks" downstream of the
      medial-temporal motion-detection area. This model is shown to account for a wide
      range of data, and to generate a variety of testable predictions. Individual
      differences in the recognition, abstraction, and encoding of trajectory
      information are expected to generate distinct object persistence judgments and
      object recognition abilities. Dominance of trajectory information over feature
      information in stored object tokens during early infancy, in particular, is
      expected to disrupt the ability to re-identify human and other individuals across
      perceptual episodes, and lead to developmental outcomes with characteristics of
      autism spectrum disorders.

PMID- 21716600
TI  - Relevance of spectral cues for auditory spatial processing in the occipital
      cortex of the blind.
AB  - We have previously shown that some blind individuals can localize sounds more
      accurately than their sighted counterparts when one ear is obstructed, and that
      this ability is strongly associated with occipital cortex activity. Given that
      spectral cues are important for monaurally localizing sounds when one ear is
      obstructed, and that blind individuals are more sensitive to small spectral
      differences, we hypothesized that enhanced use of spectral cues via occipital
      cortex mechanisms could explain the better performance of blind individuals in
      monaural localization. Using positron-emission tomography (PET), we scanned blind
      and sighted persons as they discriminated between sounds originating from a
      single spatial position, but with different spectral profiles that simulated
      different spatial positions based on head-related transfer functions. We show
      here that a sub-group of early blind individuals showing superior monaural sound
      localization abilities performed significantly better than any other group on
      this spectral discrimination task. For all groups, performance was best for
      stimuli simulating peripheral positions, consistent with the notion that spectral
      cues are more helpful for discriminating peripheral sources. PET results showed
      that all blind groups showed cerebral blood flow increases in the occipital
      cortex; but this was also the case in the sighted group. A voxel-wise covariation
      analysis showed that more occipital recruitment was associated with better
      performance across all blind subjects but not the sighted. An inter-regional
      covariation analysis showed that the occipital activity in the blind covaried
      with that of several frontal and parietal regions known for their role in
      auditory spatial processing. Overall, these results support the notion that the
      superior ability of a sub-group of early-blind individuals to localize sounds is
      mediated by their superior ability to use spectral cues, and that this ability is
      subserved by cortical processing in the occipital cortex.

PMID- 21716601
TI  - Real-time measurement of face recognition in rapid serial visual presentation.
AB  - Event-related potentials (ERPs) have been used extensively to study the processes
      involved in recognition memory. In particular, the early familiarity component of
      recognition has been linked to the FN400 (mid-frontal negative deflection between
      300 and 500 ms), whereas the recollection component has been linked to a later
      positive deflection over the parietal cortex (500-800 ms). In this study, we
      measured the ERPs elicited by faces with varying degrees of familiarity.
      Participants viewed a continuous sequence of faces with either low (novel faces),
      medium (celebrity faces), or high (faces of friends and family) familiarity while
      performing a separate face-identification task. We found that the level of
      familiarity was significantly correlated with the magnitude of both the early and
      late recognition components. Additionally, by using a single-trial classification
      technique, applied to the entire evoked response, we were able to distinguish
      between familiar and unfamiliar faces with a high degree of accuracy. The
      classification of high versus low familiarly resulted in areas under the curve of
      up to 0.99 for some participants. Interestingly, our classifier model (a linear
      discriminant function) was developed using a completely separate object
      categorization task on a different population of participants.

PMID- 21716602
TI  - Challenges in pharmacology of anti-cancer drugs - the search for addictions.

PMID- 21716603
TI  - Probing of Brain States in Real-Time: Introducing the ConSole Environment.
AB  - Recent years have seen huge advancements in the methods available and used in
      neuroscience employing EEG or MEG. However, the standard approach is to average a
      large number of trials for experimentally defined conditions in order to reduce
      intertrial-variability, i.e., treating it as a source of "noise." Yet it is now
      more and more accepted that trial-to-trial fluctuations bear functional
      significance, reflecting fluctuations of "brain states" that predispose
      perception and action. Such effects are often revealed in a pre-stimulus period,
      when comparing response variability to an invariant stimulus. However such
      offline analyses are disadvantageous as they are correlational by drawing
      conclusions in a post hoc-manner and stimulus presentation is random with respect
      to the feature of interest. A more direct test is to trigger stimulus
      presentation when the relevant feature is present. The current paper introduces
      Constance System for Online EEG (ConSole), a software package capable of
      analyzing ongoing EEG/MEG in real-time and presenting auditory and visual stimuli
      via internal routines. Stimulation via external devices (e.g., transcranial
      magnetic stimulation) or third-party software (e.g., PsyScope X) is possible by
      sending TTL-triggers. With ConSole it is thus possible to target the stimulation
      at specific brain states. In contrast to many available applications, ConSole is
      open-source. Its modular design enhances the power of the software as it can be
      easily adapted to new challenges and writing new experiments is an easy task.
      ConSole is already pre-equipped with modules performing standard signal
      processing steps. The software is also independent from the EEG/MEG system, as
      long as a driver can be written (currently two EEG systems are supported).
      Besides a general introduction, we present benchmark data regarding performance
      and validity of the calculations used, as well as three example applications of
      ConSole in different settings. ConSole can be downloaded at: http://console
      kn.sf.net.

PMID- 21716604
TI  - Behavioral assessment of emotion discrimination, emotion regulation, and
      cognitive control in childhood, adolescence, and adulthood.
AB  - Emotion discrimination, emotion regulation, and cognitive control are three
      related, yet separable processes that emerge over the course of development. The
      current study tested 100 children, adolescents, and adults on an Emotional
      Go/Nogo task, illustrating the ability of this paradigm to identify the unique
      developmental patterns for each of these three processes in the context of both
      positive (happy) and negative emotions (fear, sad, and anger), across three
      different age groups. Consistent with previous literature, our findings show that
      emotion discrimination and regulatory abilities (both cognitive control and
      emotion regulation) improve steadily for each age group, with each age group
      showing unique patterns of performance. The findings suggest that emotion
      regulation is constructed from basic cognition control and emotion discrimination
      skills. The patterns of behavior from the Emotional Go/Nogo task provide
      normative benchmark data across a wide range of emotions that can be used for
      future behavioral and neuroimaging studies that examine the developmental
      construction of emotion regulatory processes.

PMID- 21716605
TI  - The Impact of the Mode of Thought in Complex Decisions: Intuitive Decisions are
      Better.
AB  - A number of recent studies have reported that decision quality is enhanced under
      conditions of inattention or distraction (unconscious thought; Dijksterhuis,
      2004; Dijksterhuis and Nordgren, 2006; Dijksterhuis et al., 2006). These reports
      have generated considerable controversy, for both experimental (problems of
      replication) and theoretical reasons (interpretation). Here we report the results
      of four experiments. The first experiment replicates the unconscious thought
      effect, under conditions that validate and control the subjective criterion of
      decision quality. The second and third experiments examine the impact of a mode
      of thought manipulation (without distraction) on decision quality in immediate
      decisions. Here we find that intuitive or affective manipulations improve
      decision quality compared to analytic/deliberation manipulations. The fourth
      experiment combines the two methods (distraction and mode of thought
      manipulations) and demonstrates enhanced decision quality, in a situation that
      attempts to preserve ecological validity. The results are interpreted within a
      framework that is based on two interacting subsystems of decision-making: an
      affective/intuition based system and an analytic/deliberation system.

PMID- 21716606
TI  - Interpersonal synergies.
AB  - We present the perspective that interpersonal movement coordination results from
      establishing interpersonal synergies. Interpersonal synergies are higher-order
      control systems formed by coupling movement system degrees of freedom of two (or
      more) actors. Characteristic features of synergies identified in studies of
      intrapersonal coordination - dimensional compression and reciprocal compensation 
      are revealed in studies of interpersonal coordination that applied the
      uncontrolled manifold approach and principal component analysis to interpersonal
      movement tasks. Broader implications of the interpersonal synergy approach for
      movement science include an expanded notion of mechanism and an emphasis on
      interaction-dominant dynamics.

PMID- 21716607
TI  - Myofascial pain syndrome in chronic back pain patients.
AB  - BACKGROUND: Myofascial pain syndrome (MPS) is a regional musculoskeletal pain
      disorder that is caused by myofascial trigger points. The objective of this study
      was to determine the prevalence of MPS among chronic back pain patients, as well
      as to identify risk factors and the outcome of this disorder. METHODS: This was a
      prospective observational study involving 126 patients who attended the Pain
      Management Unit for chronic back pain between 1st January 2009 and 31st December
      2009. Data examined included demographic features of patients, duration of back
      pain, muscle(s) involved, primary diagnosis, treatment modality and response to
      treatment. RESULTS: The prevalence of MPS among chronic back pain patients was
      63.5% (n = 80). Secondary MPS was more common than primary MPS, making up 81.3%
      of the total MPS. There was an association between female gender and risk of
      developing MPS (chi(2) = 5.38, P = 0.02, O.R. = 2.4). Occupation, body mass index
      and duration of back pain were not significantly associated with MPS occurrence.
      Repeated measures analysis showed significant changes (P < 0.001) in Visual
      Analogue Score (VAS) and Modified Oswestry Disability Score (MODS) with standard
      management during three consecutive visits at six-month intervals. CONCLUSIONS:
      MPS prevalence among chronic back pain patients was significantly high, with
      female gender being a significant risk factor. With proper diagnosis and expert
      management, MPS has a favourable outcome.

PMID- 21716608
TI  - A case of pneumothorax after phrenic nerve block with guidance of a nerve
      stimulator.
AB  - Hiccups have more than 100 etiologies. The most common etiology has
      gastrointestinal origins, related mainly to gastric distention and
      gastroesophageal reflux disease. Intractable hiccups are rare but may present as
      a severe symptom of various diseases. Hiccups are mostly treated with non
      invasive or pharmacological therapies. If these therapies fail, invasive methods
      should be used. Here, we present a patient on whom we performed a blockage of the
      phrenic nerve with the guidance of a nerve stimulator. The patient also had
      pneumothorax as a complication. Three hours after intervention, a tube
      thoracostomy was performed. One week later, the patient was cured and discharged
      from the hospital. In conclusion, a stimulator provides the benefit of localizing
      the phrenic nerve, which leads to diaphragmatic contractions. Patients with thin
      necks have more risk of pneumothorax during phrenic nerve location.

PMID- 21716609
TI  - Administration of Vitamin C in a Patient with Herpes Zoster - A case report -.
AB  - Herpes zoster as a result of reactivated varicella-zoster virus is characterized
      by vesicular eruptions on skin and painful neuralgia in the dermatome
      distribution. Pain during an acute phase of herpes zoster has been associated
      with a higher risk of developing postherpetic neuralgia. The current therapies
      for herpes zoster including analgesics and sympathetic nerve block as well as
      antiviral agents are important to alleviate pain and prevent postherpetic
      neuralgia. However, in some cases, the pain does not respond well to these
      treatments. We had a case in which a patient with herpes zoster did not respond
      to conventional therapy so we attempted to administer intravenous infusion of
      vitamin C which resulted in an immediate reduction in the pain.

PMID- 21716610
TI  - Complex Regional Pain Syndrome (CRPS type-1) in an Adolescent Following
      Extravasation of Dextrose Containing Fluid-an Underdiagnosed Case.
AB  - Due to its complex pathophysiology and wide spectrum of clinical manifestations,
      the diagnosis of CRPS is often missed in the early stage by primary care
      physicians. After being treated by a primary care physician for 5 months for
      chronic cellulitis, a 16-year-old girl was referred to our hospital with features
      of type-1 CRPS of the right upper extremity. Inability to diagnose early caused
      prolonged suffering to the girl with all the consequence of CRPS. The patient
      responded well with marked functional recovery from multimodal therapy. Ability
      to distinguish CRPS from other pain conditions, referral for specialty care at
      the appropriate time and full awareness of this condition and its clinical
      features among various healthcare professionals are essential in reducing patient
      suffering and stopping its progression towards difficult-to-treat situations.

PMID- 21716611
TI  - Ultrasound-guided Lateral Femoral Cutaneous Nerve Block in Meralgia Paresthetica.
AB  - Meralgia paresthetica is a rarely encountered sensory mononeuropathy
      characterized by paresthesia, pain or sensory impairment along the distribution
      of the lateral femoral cutaneous nerve (LFCN) caused by entrapment or compression
      of the nerve as it crossed the anterior superior iliac spine and runs beneath the
      inguinal ligament. There is great variability regarding the area where the nerve
      pierces the inguinal ligament, which makes it difficult to perform blind
      anesthetic blocks. Ultrasound has developed into a powerful tool for the
      visualization of peripheral nerves including very small nerves such as accessory
      and sural nerves. The LFCN can be located successfully, and local anesthetic
      solution distribution around the nerve can be observed with ultrasound guidance.
      Our successfully performed ultrasound-guided blockade of the LFCN in meralgia
      paresthetica suggests that this technique is a safe way to increase the success
      rate.

PMID- 21716612
TI  - The Shoulder Pain due to Metastatic Breast Cancer -A Case Report-.
AB  - A rotator cuff tear causes shoulder pain and limits movement of the shoulder
      joint. A chronic degenerative change or impingement is the reason for a rotator
      cuff tear. Diagnosis is made based on medical history and, physical and
      radiological examinations. Other causes of shoulder pain include calcific
      tendinitis, degenerative arthropathy, joint dislocation, fracture, and primary or
      metastatic neoplasm. However, metastatic cancer in the shoulder joint is
      difficult to diagnosis. We experienced a case in which a 46-year-old female
      patient complained of left shoulder pain and limited joint mobility, and these
      symptoms were due to metastatic breast cancer in the shoulder.

PMID- 21716613
TI  - Partial-thickness rotator cuff tears.
AB  - Although the incidence of partial-thickness rotator cuff tears (PTRCTs) was
      reported to be from 13% to 32% in cadaveric studies, the actual incidence is not
      yet known. The causes of PTRCTs can be explained by either extrinsic or intrinsic
      theories. Studies suggest that intrinsic degeneration within the rotator cuff is
      the principal factor in the pathogenesis of rotator cuff tears. Extrinsic causes
      include subacromial impingement, acute traumatic events, and repetitive
      microtrauma. However, acromially initiated rotator cuff pathology does not occur
      and extrinsic impingement does not cause pathology on the articular side of the
      tendon. An arthroscopic classification system has been developed based on the
      location and depth of the tear. These include the articular, bursal, and
      intratendinous areas. Both ultrasound and magnetic resonance image are reported
      with a high accuracy of 87%. Conservative treatment, such as subacromial or intra
      articular injections and suprascapular nerve block with or without block of the
      articular branches of the circumflex nerve, should be considered prior to
      operative treatment for PTRCTs.

PMID- 21716614
TI  - Use of lidocaine patch for percutaneous endoscopic lumbar discectomy.
AB  - BACKGROUND: Lidocaine patch (L5P) has demonstrated short-term efficacy in
      treating both acute surgical pain and chronic neuropathic pain with tolerable
      side effects. Percutaneous endoscopic lumbar discectomy (PELD) is the mainstay of
      minimally invasive spine surgery (MISS). Sufficient analgesia during PELD surgery
      makes the patient consider it real MISS. This study was performed to evaluate the
      efficacy and adverse effects of lidocaine patch in patients who underwent PELD
      under local anesthesia. METHODS: L5P (L group) or placebo (P group) was randomly
      applied on the skin of the back covering the anticipated path of the working
      channel before 1 hour of surgery in 100 patients who underwent a single level
      PELD at L4-L5. Efficacy of the lidocaine patch was assessed by patient's numeric
      rating scale (NRS) of pain at each stage during the surgery and by a 5-scale
      grading of the satisfaction with the anesthesia of the operator and patients
      after surgery. RESULTS: Mean NRS scores at the stages of needle insertion, skin
      incision, serial dilation and insertion of working channel, and subcutaneous
      suture were significantly lower in the L group than the P group. Postoperative
      operator's and patients' satisfaction scores were also significantly higher in L
      group than in the P group. There were subtle adverse effects in both groups.
      CONCLUSIONS: L5P provided better pain relief during PELD, especially at the stage
      of needle insertion, skin incision, serial dilation and insertion of working
      channel, and subcutaneous suture. It also provided higher patient and operator
      postoperative satisfaction, with only subtle adverse effects.

PMID- 21716615
TI  - Value of Bone Scintigraphy and Single Photon Emission Computed Tomography (SPECT)
      in Lumbar Facet Disease and Prediction of Short-term Outcome of Ultrasound Guided
      Medial Branch Block with Bone SPECT.
AB  - BACKGROUND: Facet joint disease plays a major role in axial low-back pain. Few
      diagnostic tests and imaging methods for identifying this condition exist. Single
      photon emission computed tomography (SPECT) is reported that it has a high
      sensitivity and specificity in diagnosing facet disease. We prospectively
      evaluated the use of bone scintigraphy with SPECT for the identification of
      patients with low back pain who would benefit from medial branch block. METHODS:
      SPECT was performed on 33 patients clinically suspected of facet joint disease.
      After SPECT, an ultrasound guided medial branch block was performed on all
      patients. On 28 SPECT-positive patients, medial branch block was performed based
      on the SPECT findings. On 5 negative patients, medial branch block was performed
      based on clinical findings. For one month, we evaluated the patients using the
      visual analogue scale (VAS) and Oswestry disability index. SigmaStat and paired t
      tests were used to analyze patient data and compare results. RESULTS: Of the 33
      patients, the ones who showed more than 50% reduction in VAS score were assigned
      'responders'. SPECT positive patients showed a better response to medial branch
      blocks than negative patients, but no changes in the Oswestry disability index
      were seen. CONCLUSIONS: SPECT is a sensitive tool for the identification of facet
      joint disease and predicting the response to medial branch block.

PMID- 21716616
TI  - Piriformis muscle: clinical anatomy with computed tomography in korean
      population.
AB  - BACKGROUND: The objective was to evaluate the distance from the skin and the
      diameter of the piriformis muscle and their relationship to the body mass index
      (BMI). METHODS: The study was a prospective study involving 60 patients. Patients
      were prepared on a radiological table in the prone position. Several images were
      obtained of each. In this view, the distance between the subcutaneous tissue and
      the piriformis muscle, and the diameter of the piriformis, were measured at three
      points (medially to laterally). RESULTS: The distance to the piriformis from the
      skin was 6.6 +/- 0.9 cm, 6.3 +/- 0.8 cm, and 5.2 +/- 0.9 cm in terms of the
      lateral, center, and medial measurement, respectively. The center of the
      piriformis had a greater diameter with 1.7 +/- 0.4 (0.9-2.5) cm. The distance to
      the piriformis increased with BMI. CONCLUSIONS: This study shows that the lateral
      of the piriformis muscle has a relatively greater distance from the skin. The
      center of the piriformis showed a greater diameter than other two portions. We
      found that the distance of the piriformis from subcutaneous tissues was
      correlated with BMI, but the diameter of the piriformis was not affected by BMI.
      These measurements can be used as a reference for determining the piriformis
      injection site in patients with piriformis syndrome.

PMID- 21716617
TI  - Piriformis syndrome in knee osteoarthritis patients after wearing rocker bottom
      shoes.
AB  - BACKGROUND: Rocker bottom shoes (RBS) are popular among patients with different
      foot, leg, or back problems in Korea. Patients with knee osteoarthritis
      concurrent weakness in the quadriceps femoris muscle, who wear these shoes, are
      often assumed to develop piriformis syndrome (PS). This study was performed to
      improve the understanding about the effect of wearing such shoes on duration of
      the syndrome in knee osteoarthritis. METHODS: We randomly assigned 150 patients
      with PS, who had used RBS daily for at least 6 months, to 2 groups, the S
      (stopped wearing) and K (kept wearing) groups. Both the groups were subdivided
      into the O and N groups, comprising patients with and without knee
      osteoarthritis, respectively. The effects of the treatment, including piriformis
      muscle injections and a home exercise program, were compared between the 2 groups
      by using a flexion-adduction-internal rotation (FAIR) test, a numeric rating
      scale (NRS), and the revised Oswestry disability index (ODI) during the 12-week
      follow-up. RESULTS: The positive FAIR test ratios, mean NRS scores, and revised
      ODIs were higher in the KO group than the SN group from 4?12 weeks after
      treatment. CONCLUSIONS: RBS may extend duration of the PS in osteoarthritis
      patients.

PMID- 21716618
TI  - Isolation and identification of phenolic compounds from Gynura divaricata leaves.
AB  - BACKGROUND: Phenolic constituents were the principle bioactivity compounds exist
      in Gynura divaricata, little phenolic compounds were reported from the plant
      previously. MATERIALS AND METHODS: 60% ethanol extract from the leaves of Gynura
      divaricata were isolated and purified by column chromatography of Silica gel, ODS
      and Sephadex LH-20, the structures of the isolated compounds were identified by
      UV, 1H-NMR, 13C-NMR and MS spectroscopic techniques. Additionally, a high
      performance liquid chromatography-diode array detector-electrospray ionization
      mass (HPLC-DAD-ESI-MS) analytical method was developed to identify some minor
      constituents in the n-butanol fraction of the ethanol extract of Gynura
      divaricata. RESULTS: Six flavonols and one Dicaffeoylquinic acid were isolated
      from the leaves of Gynura divaricata, and these compounds were identified as
      follows: quercetin (1), kaempferol (2), kaempferol-3-O-beta-D-glucopyranoside
      (3), quercetin-3-O-rutinoside (4), kaempferol-3,7-di-O-beta-D-glucopyranoside
      (5), kaempferol-3-O-rutinoside-7-O-beta-D-glucopyranoside (6), and 3,5
      dicaffeoylquinic acid (7). A total of 13 compounds, including 9 flavonol
      glycosides and 4 phenolic acids, were tentatively identified by comparing their
      retention time (RT), UV, and MS spectrum values with those that had been
      identified and the published data. CONCLUSION: This was the first time to use the
      HPLC-DAD-ESI-MS method to identify the phytochemicals of the genera Gynura.
      Moreover, compounds (6) and (7) have been isolated for the first time from the
      genus Gynura.

PMID- 21716619
TI  - Isolation of biologically active constituents from Moringa peregrina (Forssk.)
      Fiori. (family: Moringaceae) growing in Egypt.
AB  - BACKGROUND: Moringa peregrina is a wild plant that grown in the eastern desert
      mountains in Egypt. Although, this plant is native to Egypt, no details studies
      were traced on its chemical composition and biological activity. MATERIALS AND
      METHODS: The different fractions of the ethanolic extract of the dried aerial
      parts of the plants were subjected to fractionation and purification on various
      silica and sephadex columns for the isolation of the major compounds which were
      tested for there anticancer activity. The aqueous and ethanolic extract as well
      as its different fractions were tested for antihyperglycemic effect on
      Streptozitocin-induced diabetes in rats. RESULTS: Investigation of the different
      fractions of the ethanolic extract of the aerial parts of M. peregrina yielded
      lupeol acetate (1), beta-amyrin (2), alpha-amyrin (3), beta-sitosterol (4), beta
      sitosterol-3-O-glucoside (5), apigenin (6), rhamnetin (7), neochlorogenic acid
      (10), rhamnetin-3-O-rutinoside (12), and 6-methoxy-acacetin-8-C-beta-glucoside
      (13) which were isolated for the first time from the plant. Compound (13) was
      isolated for the first time from genus Moringa. In addition, quercetin (8),
      chryseriol-7-O-rhamnoside (9) and quercetin-3-O-rutinoside (11) were also
      isolated. Identification has been established by spectral data (UV, MS, IR, 1H,
      1H -1H COSY, and 13C-NMR). The major isolated compounds were found to have
      valuable cytotoxic activities against breast (MCF 7) and colon (HCT 116) cancer
      cell lines and their activities were comparable to the reference drug
      doxorubicin. On the other hand, the aqueous and ethanolic extracts as well as the
      n-hexane fraction were found to have potent antihyperglycemic effect on
      Streptozitocin-induced diabetes in rats. CONCLUSION: The Egyptian plant M.
      peregrina is rich in biologically active ingredients which showed potent
      cytotoxic activity and also its ethanolic extraxt exert a significant
      antihyperglycemic effect.

PMID- 21716620
TI  - Essential oil composition analysis of three cultivars seeds of Resina ferulae
      from Xinjiang, China.
AB  - OBJECTIVE: Three cultivars seeds of Resina ferulae were analyzed for essential
      oil composition, Ferula sinkiangensis K. M. Shen, Ferula fukangensis K. M. Shen,
      and Ferula ovina, investigated differences among different genera of medicinal R.
      ferulae. MATERIALS AND METHODS: The essential oils were extracted by the method
      of hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC
      MS), using normalization method to calculate relative amount. RESULTS: Twenty-six
      compounds were identified in F. sinkiangensis K. M. Shen, comprised 99.001% of
      total essential oil; 21 compounds were identified in F. fukangensis K. M. Shen,
      comprised 100% of total essential oil; 25 compounds were identified in F. ovina,
      comprised 99.459% of total essential oil. n-Propyl sec-butyl disulfide is the
      main component in three cultivars seeds of R. ferulae, accounting for 55.875%,
      49.797%, 53.781%, respectively. CONCLUSION: Little diversity among three
      cultivars seeds of R. ferulae from Xinjiang.

PMID- 21716621
TI  - Membrane stability of sickle erythrocytes incubated in extracts of three
      medicinal plants: Anacardium occidentale, Psidium guajava, and Terminalia
      catappa.
AB  - BACKGROUND: Many reports showed that medicinal plant extracts cause alterations
      on the shape and physiology of erythrocytes. OBJECTIVE: The present study seeks
      to ascertain the osmotic stability of sickle erythrocytes incubated in aqueous
      extracts of Anacardium occidentale, Psidium guajava, and Terminalia catappa.
      MATERIALS AND METHODS: The fraction of erythrocytes lysed when suspended in
      saline solution of varying concentrations was investigated by spectrophotometric
      method. The percentage hemolysis of erythrocytes in the control and test samples
      showed a sigmoidal relationship with increasing concentrations of saline
      solution. Membrane stability was ascertained as mean corpuscular fragility (MCF)
      index of erythrocytes incubated in 400 and 800 mg/dL aqueous concentrations of
      the three plant extracts. RESULTS: The two experimental concentrations of P.
      guajava and T. catappa protected the erythrocytes against osmotic stress, as
      evidenced by decreases in the values of MCF compared with the control sample (P <
      0.05). However, 800 mg/dL of A. occidentale promoted significant (P < 0.05)
      distabilization of sickle erythrocytes. CONCLUSION: Whereas the two experimental
      concentrations of aqueous extracts of P. guajava and T. catappa stabilized
      erythrocyte membrane, higher concentration (800 mg/dL) of A. occidentale
      exhibited no membrane protective effect.

PMID- 21716622
TI  - Sodium metabisulfite-induced polymerization of sickle cell hemoglobin incubated
      in the extracts of three medicinal plants (Anacardium occidentale, Psidium
      guajava, and Terminalia catappa).
AB  - BACKGROUND: The exploitation and utilization of vast varieties of herbal extracts
      may serve as alternative measures to deter aggregation of deoxygenated sickle
      cell hemoglobin (deoxyHbS) molecules. OBJECTIVE: The present in vitro study
      ascertained the capacity of three medicinal plants, namely, Anacardium
      occidentale, Psidium guajava, and Terminalia catappa, to alter polymerization of
      HbS. MATERIALS AND METHODS: Spectrophotometric method was used to monitor the
      level of polymerization of hemolysate HbS molecules treated with sodium
      metabisulfite (Na(2) S(2) O(5)) at a regular interval of 30 s for a period of 180
      s in the presence of separate aqueous extracts of A. occidentale, P. guajava, and
      T. catappa. At time intervals of 30 s, the level of polymerization was expressed
      as percentage of absorbance relative to the control sample at the 180th s.
      RESULTS: Although extracts of the three medicinal plants caused significant (P <
      0.05) reduction in polymerization of deoxyHbS molecules, the corresponding
      capacity in this regard diminished with increase in incubation time. Aqueous
      extract of P. guajava exhibited the highest capacity to reduced polymerization of
      deoxyHbS molecules. Whereas at t > 60 s, extract concentration of 400 mg% of A.
      occidentale activated polymerization of deoxyHbS molecules by 6.23+/-1.34,
      14.53+/-1.67, 21.15+/-1.89, and 24.42+/-1.09%, 800 mg% of T. catappa at t > 30 s
      gave values of 2.50+/-1.93, 5.09+/-1.96, 10.00+/-0.99, 15.38+/-1.33, and 17.31+/
      0.97%. CONCLUSION: The capacity of the three medicinal plants to interfere with
      polymerization of deoxyHbS molecules depended on the duration of incubation and
      concentration of the extracts.

PMID- 21716623
TI  - Protective effects on myelosuppression mice treated by three different classic
      Chinese medicine formulae.
AB  - BACKGROUND: In order to observe the protective therapeutic action and mechanism
      of Liuwei Dihuang Decoction, Buzhong Yiqi Decoction, and Compound Danshen
      Decoction on Myelosuppression induced by cyclophosphamide. MATERIALS AND METHODS:
      The mice model was established by intraperitoneal injected with 100 mg/kg
      cyclophosphamide by human and mice dose conversion on the 9(th), 11(th), 13(th)
      days during the experiment. Flow cytometry (FCM) was used for detecting the
      number of cells and investigating bone marrow cell cycles. Spleen was taken out
      and the mRNA expression level of thrombopoietin (TPO) and c-Mpl were detected by
      Q-PCR, and c-Mpl in spleen in order to discuss the mechanism of myelosuppression
      and the protective effects of traditional Chinese medicine. RESULTS: Both Liuwei
      Dihuang Decoction Group and Buzhong Yiqi Decoction Group can accelerate bone
      marrow hematopoietic stem progenitor cells (HSPCs) in marrow-suppressed mice and
      enhance cell proliferation by promoting cell cycles from G0/G1 phase to access
      into S, G2/M phase. And at the same time these Chinese decoctions can increase
      the mRNA expression level of TPO and c-Mpl in spleen. CONCLUSION: Researched
      showed that Chinese formula take effect by affecting these genes on
      myelosuppressed mice.

PMID- 21716624
TI  - The effects of oral Ginkgo biloba supplementation on radiation-induced oxidative
      injury in the lens of rat.
AB  - BACKGROUND: The aim of this study was to evaluate the antioxidant role of Ginkgo
      biloba (GB) against radiation-induced cataract in the rat lens after total
      cranial irradiation with a single 5 Gray (Gy) dose of gamma irradiation.
      MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were used for the
      experiment. The rats were randomly divided into three equal groups. Group 1 did
      not receive GB or irradiation (control group) but received 1-ml saline orally
      plus sham-irradiation. Group 2 received total cranium 5 Gy of gamma irradiation
      as a single dose (IR group) plus 1-ml saline orally. Group 3 received total
      cranium irradiation plus 40 mg/kg/day GBE (IR plus GBE group). Biochemical
      parameters measured in murine lenses were carried out using spectrophotometric
      techniques. RESULTS: Lens total (enzymatic plus non-enzymatic) superoxide
      scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA),
      glutathione reductase (GRD), and glutathione-S- transferase (GST) activities
      significantly increased in the IR plus GBE groups when compared with the IR
      group. However, TSSA, GRD and GST activities were significantly lower in the IR
      group when compared with the control group. Lens xanthine oxidase (XO) activity
      in the IR group significantly increased compared to that of both the control and
      IR plus GBE groups. CONCLUSION: GBE has clear antioxidant properties and is
      likely to be a valuable drug for protection against gamma-irradiation and/or be
      used as an antioxidant against oxidative stress.

PMID- 21716625
TI  - Phytochemical investigation and hair growth studies on the rhizomes of
      Nardostachys jatamansi DC.
AB  - Nardostachys jatamansi DC rhizomes were subjected to extraction, fractionation,
      and isolation of terpenoid compounds. Three terpenoid compounds were isolated
      which are nardal, jatamansic acid, and nardin. These compounds were identified
      based on physical and spectral data (UV, IR,(1)H and(13)C NMR, 2D NMR, Mass) and
      comparison with authentic compounds. The crude extract, fractions, and two of the
      isolated compounds were tested for their hair growth activity. The hair growth
      studies showed good activities for the extract, fraction, and the isolated
      compounds.

PMID- 21716626
TI  - Diagnosis of persistent primitive olfactory artery using computed tomography
      angiography.
AB  - Persistent primitive olfactory artery (PPOA) is a rare anomaly of the anterior
      cerebral artery. We present one case of PPOA incidentally diagnosed with the aid
      of computed tomography (CT) angiography. A 24-year-old woman was admitted to our
      hospital after sudden onset of vertigo. Three-dimensional CT angiography revealed
      an anomalous artery arising from the terminal portion of the right internal
      carotid artery. The proximal portion of the anomalous artery coursed
      anteromedially and made a hairpin turn posterosuperior to the midline. PPOA may
      be overlooked because of its rarity, but CT angiography can be useful in
      detecting this rare vascular anomaly. Follow-up study is necessary in our case to
      confirm whether an aneurysm occurs on the PPOA.

PMID- 21716627
TI  - Intraventricular atypical meningiomas.
AB  - A rare case of intraventricular meningioma that arose in the atrium of the left
      lateral ventricle was identified in a 51-year-old woman. Gross total removal was
      performed by transcortical approach. Histopathological findings showed
      meningothelial meningioma with a focal atypical area which had 8% of Ki-67
      labeling index (LI). A large recurrence extending into the ipsilateral
      quadrigeminal cistern and opposite medial occipital lobe developed approximately
      41 months after the first operation. The specimens obtained from the second
      resection showed atypical meningioma with 20% of Ki-67 LI but there were no
      anaplastic area. The patient underwent fractionated stereotactic radiotherapy.
      However, multiple local distant metastases were found in the occipital and
      cerebellar cortex suggesting cerebrospinal fluid dissemination apparently 24
      months after the second operation. This report presents chronological progression
      of a rare intraventricular atypical meningioma with more aggressive
      transformation.

PMID- 21716628
TI  - Isolated spinal neurocysticercosis : unusual ocular presentation mimicking
      pseudotumor cerebri.
AB  - Spinal intradural cysticercosis is a rare manifestation of neurocysticercosis. We
      report a unique patient who showed visual symptoms and normal imaging of the
      brain caused by isolated spinal neurocysticercosis. A 59-year-old male patient
      was admitted to the emergency unit with a history of severe headache and
      progressive blurred vision. Brain computed tomographic scanning and magnetic
      resonance imaging showed normal cerebral anatomy without hydrocephalus. The
      fundoscopic evaluation by an ophthalmologist showed bilateral papilledema.
      Perimetry studies revealed visual field defects in both eyes. With the diagnosis
      of pseudotumor cerebri, a lumbar tap was attempted; however, we could not drain
      the cerebrospinal fluid in spite of appropriate attempts. Lumbar magnetic
      resonance imaging revealed multilevel intraspinal lesions that were confirmed
      histologically to be neurocysticercosis. An intraoperative lumbar puncture
      revealed an increased opening pressure and cytochemical analysis showed elevated
      cerebrospinal fluid protein level. The headache resolved immediately after
      surgery. However, the visual symptoms remained and recovered only marginally
      despite antihelminthic medications after six months of operation.

PMID- 21716629
TI  - Spinal extradural meningeal cyst in klippel-trenaunay syndrome.
AB  - A case of a symptomatic spinal extradural meningeal cyst (SEMC) in Klippel
      Trenaunay syndrome (KTS) is introduced. A 38-year-old woman presented with right
      L2 radiculopathy. She underwent operations for varicose veins in both her lower
      extremities. She had port-wine nevi on her trunk and extremities. The edematous
      change in both legs had waxed and waned. Magnetic resonance imaging showed an
      11.8*13 mm extradural meningeal cyst growing through the intervertebral foramen
      in L2-3. Multiple meningeal cysts were located in the dorsal aspect of the spinal
      cord from T3 to T10. A 5.8*6.2 mm cyst was also found in left pleural cavity. The
      extradural meningeal cyst was completely excised and the preoperative symptom was
      improved. KTS is a congenital disorder due to a mesodermal abnormality, which may
      predispose the dura to weakness. The SEMC may occur through the dural defect or
      weakened point.

PMID- 21716630
TI  - Thoracic intramedullary schwannoma accompanying by extramedullary beads-like
      daughter schwanommas.
AB  - Thoracic intramedullary schwannomas are rare spinal cord tumors. Most of these
      tumors have been reported as a single lesion in the spinal cord. The authors
      report the first case of intramedullary schwannoma accompanying by extramedullary
      beads-like daughter masses of the thoracic spine. A 68-year-old male presented
      with walking disturbance and decreased sensation below T10 dermatome. Imaging
      workup revealed an intramedullary mass at T6 and T7. T6 and T7 laminectomy and
      mass removal were performed. Intraoperatively, extramedullary beads-like daughter
      masses along the nerve roots adjacent to intramedullary mass were identified.
      Total removal of intramedullary lesion and partial resection of extramedullary
      masses were done. Histological analysis confirmed the diagnosis of schwannoma.
      The patient could ambulate independently at postoperative 1 month without any
      neurological sequelae. The authors experienced a surgical case of intramedullary
      schwannoma accompanying by extramedullary beads-like same pathologies in the
      thoracic spine.

PMID- 21716631
TI  - Concurrent nocardia related brain abscess and semi-invasive pulmonary
      aspergillosis in an immunocompetent patient.
AB  - We describe here the first case of a concurrent brain abscess caused by Norcardia
      spp. and semi-invasive pulmonary aspergillosis in an immunocompetent patient.
      After one year of appropriate antimicrobial therapy and surgical drainage of the
      brain abscess, the nocardia brain abscess and pulmonary aspergillosis have
      resolved.

PMID- 21716632
TI  - Posterior cervical inclinatory foraminotomy for spondylotic radiculopathy
      preliminary.
AB  - Posterior cervical foraminotomy is an attractive therapeutic option in selected
      cases of cervical radiculopathy that maintains cervical range of motion and
      minimize adjacent-segment degeneration. The focus of this procedure is to
      preserve as much of the facet as possible with decompression. Posterior cervical
      inclinatory foraminotomy (PCIF) is a new technique developed to offer excellent
      results by inclinatory decompression with minimal facet resection. The highlight
      of our PCIF technique is the use of inclinatory drilling out for preserving more
      of facet joint. The operative indications are radiculopathy from cervical
      foraminal stenosis (single or multilevel) with persistent or recurrent root
      symptoms. The PCIFs were performed between April 2007 and December 2009 on 26
      male and 8 female patients with a total of 55 spinal levels. Complete and partial
      improvement in radiculopathic pain were seen in 26 patients (76%), and 8 patients
      (24%), respectively, with preserving more of facet joint. We believe that PCIF
      allows for preserving more of the facet joint and capsule when decompressing
      cervical foraminal stenosis due to spondylosis. We suggest that our PCIF
      technique can be an effective alternative surgical approach in the management of
      cervical spondylotic radiculopathy.

PMID- 21716633
TI  - Effects of working memory load on visual selective attention: behavioral and
      electrophysiological evidence.
AB  - Working memory and attention interact in a way that enables us to focus on
      relevant items and maintain current goals. The influence of working memory on
      attention has been noted in several studies using dual task designs. Multitasking
      increases the demands on working memory and reduces the amount of resources
      available for cognitive control functions such as resolving stimulus conflict.
      However, few studies have investigated the temporal activation of the cortex
      while multitasking. The present study addresses the extent to which working
      memory load influences early (P1) and late (P300) attention-sensitive event
      related potential components using a dual task paradigm. Participants performed
      an arrow flanker task alone (single task condition) or concurrently with a
      Sternberg memory task (dual task condition). In the flanker task, participants
      responded to the direction of a central arrow surrounded by congruent or
      incongruent arrows. In the dual task condition, participants were presented with
      a Sternberg task that consisted of either four or seven consonants to remember
      prior to a short block of flanker trials. Participants were slower and less
      accurate on incongruent versus congruent trials. Furthermore, accuracy on
      incongruent trials was reduced in both dual task conditions. Likewise, P300
      amplitude to incongruent flanker stimuli decreased when working memory load
      increased. These findings suggest that interference from incongruent flankers was
      more difficult to suppress when working memory was taxed. In addition, P1
      amplitude was diminished on all flanker trials in the dual task condition. This
      result indicates that top-down attentional control over early visual processing
      is diminished by increasing demands on working memory. Both the behavioral and
      electrophysiological results suggest that working memory is critical in
      maintaining attentional focus and resolving conflict.

PMID- 21716634
TI  - Differential calcium dependence of axonal versus somatodendritic dopamine
      release, with characteristics of both in the ventral tegmental area.
AB  - Midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and
      ventral tegmental area (VTA) exhibit somatodendritic release of DA. Previous
      studies indicate a difference between the Ca(2+) dependence of somatodendritic DA
      release in the SNc and that of axonal DA release in dorsal striatum. Here, we
      evaluated the Ca(2+) dependence of DA release in the VTA and nucleus accumbens
      (NAc) shell for comparison with that in the SNc and dorsal striatum. Release of
      DA was elicited by single-pulse stimulation in guinea-pig brain slices and
      monitored with subsecond resolution using carbon-fiber microelectrodes and fast
      scan cyclic voltammetry. In dorsal striatum and NAc, DA release was not
      detectable at extracellular Ca(2+) concentrations ([Ca(2+)](o)) below 1 mM;
      however, a progressive increase in evoked extracellular DA concentration
      ([DA](o)) was seen with [Ca(2+)](o) >= 1.5 mM. By contrast, in SNc and VTA,
      robust increases in [DA](o) could be elicited in 0.25 mM [Ca(2+)](o) that were
      ~60% of those seen in 1.5 mM [Ca(2+)](o). In SNc, a plateau in single-pulse
      evoked [DA](o) was seen at [Ca(2+)](o) >= 1.5 mM, mirroring the release plateau
      reported previously for pulse-train stimulation in SNc. In VTA, however, evoked
      [DA](o) increased progressively throughout the range of [Ca(2+)](o) tested (up to
      3.0 mM). These functional data are consistent with the microanatomy of the VTA,
      which includes DA axon collaterals as well as DA somata and dendrites.
      Differences between axonal and somatodendritic release data were quantified using
      Hill analysis, which showed that the Ca(2+) dependence of axonal DA release is
      low affinity with high Ca(2+) cooperativity, whereas somatodendritic release is
      high affinity with low cooperativity. Moreover, this analysis revealed the dual
      nature of DA release in the VTA, with both somatodendritic and axonal
      contributions.

PMID- 21716635
TI  - The Subthalamic Nucleus becomes a Generator of Bursts in the Dopamine-Depleted
      State. Its High Frequency Stimulation Dramatically Weakens Transmission to the
      Globus Pallidus.
AB  - Excessive burst firing in the dopamine-depleted basal ganglia correlates with
      severe motor symptoms of Parkinson's disease that are attenuated by high
      frequency electrical stimulation of the subthalamic nucleus (STN). Here we test
      the hypothesis that pathological bursts in dopamine-deprived basal ganglia are
      generated within the STN and transmitted to globus pallidus neurons. To answer
      this question we recorded excitatory synaptic currents and potentials from
      subthalamic and pallidal neurons in the basal ganglia slice (BGS) from dopamine
      depleted mice while continuously blocking GABA(A) receptors. In control mice, a
      single electrical stimulus delivered to the internal capsule or the rostral pole
      of the STN evoked a short duration, small amplitude, monosynaptic EPSC in
      subthalamic neurons. In contrast, in the dopamine-depleted BGS, this monosynaptic
      EPSC was amplified and followed by a burst of polysynaptic EPSCs that eventually
      reverberated three to seven times, providing a long lasting response that gave
      rise to bursts of EPSCs and spikes in GP neurons. Repetitive (10-120 Hz)
      stimulation delivered to the STN in the dopamine-depleted BGS attenuated STN
      evoked bursts of EPSCs in pallidal neurons after several minutes of stimulation
      but only high frequency (90-120 Hz) stimulation replaced them with small
      amplitude EPSCs at 20 Hz. We propose that the polysynaptic pathway within the STN
      amplifies subthalamic responses to incoming excitation in the dopamine-depleted
      basal ganglia, thereby transforming the STN into a burst generator and entraining
      pallidal neurons in pathogenic bursting activities. High frequency stimulation of
      the STN prevents the transmission of this pathological activity to globus
      pallidus and imposes a new glutamatergic synaptic noise on pallidal neurons.

PMID- 21716636
TI  - Can you hear me now? Musical training shapes functional brain networks for
      selective auditory attention and hearing speech in noise.
AB  - Even in the quietest of rooms, our senses are perpetually inundated by a barrage
      of sounds, requiring the auditory system to adapt to a variety of listening
      conditions in order to extract signals of interest (e.g., one speaker's voice
      amidst others). Brain networks that promote selective attention are thought to
      sharpen the neural encoding of a target signal, suppressing competing sounds and
      enhancing perceptual performance. Here, we ask: does musical training benefit
      cortical mechanisms that underlie selective attention to speech? To answer this
      question, we assessed the impact of selective auditory attention on cortical
      auditory-evoked response variability in musicians and non-musicians. Outcomes
      indicate strengthened brain networks for selective auditory attention in
      musicians in that musicians but not non-musicians demonstrate decreased
      prefrontal response variability with auditory attention. Results are interpreted
      in the context of previous work documenting perceptual and subcortical advantages
      in musicians for the hearing and neural encoding of speech in background noise.
      Musicians' neural proficiency for selectively engaging and sustaining auditory
      attention to language indicates a potential benefit of music for auditory
      training. Given the importance of auditory attention for the development and
      maintenance of language-related skills, musical training may aid in the
      prevention, habilitation, and remediation of individuals with a wide range of
      attention-based language, listening and learning impairments.

PMID- 21716637
TI  - Cocaine Exposure and Children's Self-Regulation: Indirect Association via
      Maternal Harshness.
AB  - OBJECTIVES: This study examined the association between prenatal cocaine exposure
      and children's self-regulation at 3 years of child age. In addition to direct
      effects of prenatal cocaine exposure on children's self-regulation, we
      hypothesized there would be indirect associations between cocaine exposure and
      self-regulation via higher maternal harshness and poor autonomic regulation in
      infancy. METHODS: The sample consisted of 216 mother-infant dyads recruited at
      delivery from local area hospitals (116 cocaine-exposed, 100 non-exposed). Infant
      autonomic regulation was measured at 7 months of age during an anger/frustration
      task, maternal harshness was coded from observations of mother-toddler
      interactions at 2 years of age, and children's self-regulation was measured at 3
      years of age using several laboratory paradigms. RESULTS: Contrary to hypotheses,
      there were no direct associations between maternal cocaine use during pregnancy
      and children's self-regulation. However, results from testing our conceptual
      model including the indirect effects via maternal harshness or infant
      parasympathetic regulation indicated that this model fit the data well, chi(2)
      (23) = 34.36, p > 0.05, Comparative Fit Index = 0.95, RMSEA = 0.05. Cocaine using
      mothers displayed higher intensity of harshness toward their toddlers during lab
      interactions across a variety of tasks at 2 years of age (beta = 0.23, p < 0.05),
      and higher intensity of harshness at 2 years was predictive of lower self
      regulation at 3 years (beta = -0.36, p < 0.01). Maternal cocaine use was also
      predictive of a non-adaptive increase in respiratory sinus arrhythmia (RSA) from
      baseline to the negative affect task, but RSA change in infancy was not
      predictive of self-regulation at 3 years. CONCLUSION: RESULTS are supportive of
      animal models indicating higher aggression among cocaine treated dams, and
      indicate that higher maternal harshness among cocaine using mothers is predictive
      of child self-regulatory outcomes in the preschool period.

PMID- 21716638
TI  - Symbolic behavior in regular classrooms: a specification of symbolic and non
      symbolic behavior.
AB  - Students' capabilities to use symbolic information in classroom setting could be
      expected to influence their possibilities to be active and participating. The
      development of strategies for teachers to compensate for reduced capability need
      specific operational definition of symbolic behavior. Fifty-three students, aged
      11-13 years old, 29 boys and 24 girls, from three classes in the same Swedish
      compulsory regular school participated in the current study. After a short
      training sequence 25 students (47%) were defined as showing symbolic behavior
      (symbolic), and 28 students (53%) were not (non-symbolic), based on their follow
      up test performances. Symbolic and non-symbolic differed significantly on post
      test performances (p < 0.05). Surprisingly, non-symbolic behavior deteriorated
      their performance, while symbolic enhanced their performance (p < 0.05). The
      results indicate that the operational definition used in the present study may be
      useful in further studies relating the capability to show symbolic behavior and
      students' activity and participation in classroom settings.

PMID- 21716639
TI  - Neurophysiological influence of musical training on speech perception.
AB  - Does musical training affect our perception of speech? For example, does learning
      to play a musical instrument modify the neural circuitry for auditory processing
      in a way that improves one's ability to perceive speech more clearly in noisy
      environments? If so, can speech perception in individuals with hearing loss (HL),
      who struggle in noisy situations, benefit from musical training? While music and
      speech exhibit some specialization in neural processing, there is evidence
      suggesting that skills acquired through musical training for specific acoustical
      processes may transfer to, and thereby improve, speech perception. The
      neurophysiological mechanisms underlying the influence of musical training on
      speech processing and the extent of this influence remains a rich area to be
      explored. A prerequisite for such transfer is the facilitation of greater
      neurophysiological overlap between speech and music processing following musical
      training. This review first establishes a neurophysiological link between musical
      training and speech perception, and subsequently provides further hypotheses on
      the neurophysiological implications of musical training on speech perception in
      adverse acoustical environments and in individuals with HL.

PMID- 21716640
TI  - Microbial communities and chemosynthesis in yellowstone lake sublacustrine
      hydrothermal vent waters.
AB  - Five sublacustrine thermal spring locations from 1 to 109 m water depth in
      Yellowstone Lake were surveyed by 16S ribosomal RNA gene sequencing in relation
      to their chemical composition and dark CO(2) fixation rates. They harbor distinct
      chemosynthetic bacterial communities, depending on temperature (16-110 degrees C)
      and electron donor supply (H(2)S <1 to >100 MUM; NH(3) <0.5 to >10 MUM). Members
      of the Aquificales, most closely affiliated with the genus Sulfurihydrogenibium,
      are the most frequently recovered bacterial 16S rRNA gene phylotypes in the
      hottest samples; the detection of these thermophilic sulfur-oxidizing autotrophs
      coincided with maximal dark CO(2) fixation rates reaching near 9 MUM C h(-1) at
      temperatures of 50-60 degrees C. Vents at lower temperatures yielded mostly
      phylotypes related to the mesophilic gammaproteobacterial sulfur oxidizer
      Thiovirga. In contrast, cool vent water with low chemosynthetic activity yielded
      predominantly phylotypes related to freshwater Actinobacterial clusters with a
      cosmopolitan distribution.

PMID- 21716641
TI  - The organization and evolution of dorsal stream multisensory motor pathways in
      primates.
AB  - In Prosimian primates, New World monkeys, and Old World monkeys microstimulation
      with half second trains of electrical pulses identifies separate zones in
      posterior parietal cortex (PPC) where reaching, defensive, grasping, and other
      complex movements can be evoked. Each functional zone receives a different
      pattern of visual and somatosensory inputs, and projects preferentially to
      functionally matched parts of motor and premotor cortex. As PPC is a relatively
      small portion of cortex in most mammals, including the close relatives of
      primates, we suggest that a larger, more significant PPC emerged with the first
      primates as a region where several ethologically relevant behaviors could be
      initiated by sensory and intrinsic signals, and mediated via connections with
      premotor and motor cortex. While several classes of PPC modules appear to be
      retained by all primates, elaboration and differentiation of these modules likely
      occurred in some primates, especially humans.

PMID- 21716642
TI  - Robust transient dynamics and brain functions.
AB  - In the last few decades several concepts of dynamical systems theory (DST) have
      guided psychologists, cognitive scientists, and neuroscientists to rethink about
      sensory motor behavior and embodied cognition. A critical step in the progress of
      DST application to the brain (supported by modern methods of brain imaging and
      multi-electrode recording techniques) has been the transfer of its initial
      success in motor behavior to mental function, i.e., perception, emotion, and
      cognition. Open questions from research in genetics, ecology, brain sciences,
      etc., have changed DST itself and lead to the discovery of a new dynamical
      phenomenon, i.e., reproducible and robust transients that are at the same time
      sensitive to informational signals. The goal of this review is to describe a new
      mathematical framework - heteroclinic sequential dynamics - to understand self
      organized activity in the brain that can explain certain aspects of robust
      itinerant behavior. Specifically, we discuss a hierarchy of coarse-grain models
      of mental dynamics in the form of kinetic equations of modes. These modes compete
      for resources at three levels: (i) within the same modality, (ii) among different
      modalities from the same family (like perception), and (iii) among modalities
      from different families (like emotion and cognition). The analysis of the
      conditions for robustness, i.e., the structural stability of transient
      (sequential) dynamics, give us the possibility to explain phenomena like the
      finite capacity of our sequential working memory - a vital cognitive function -,
      and to find specific dynamical signatures - different kinds of instabilities - of
      several brain functions and mental diseases.

PMID- 21716643
TI  - Possible functions of prefrontal cortical neurons in duration discrimination.

PMID- 21716644
TI  - Dynamic expression of notch signaling genes in neural stem/progenitor cells.
AB  - In neural stem/progenitor cells, expression of the Notch effector Hes1, a
      transcriptional repressor, oscillates with a period of 2-3 h by negative
      feedback, and Hes1 oscillations induce the oscillatory expression of the
      proneural gene Neurogenin2 (Ngn2) and the Notch ligand gene Delta-like1 (Dll1).
      Dll1 oscillation leads to the mutual activation of Notch signaling between
      neighboring cells, thereby maintaining a group of cells in the undifferentiated
      state. Not all cells express Hes1 in an oscillatory manner: cells in boundary
      regions such as the isthmus express Hes1 in a sustained manner, and these cells
      are rather dormant with regard to proliferation and differentiation. Thus, Hes1
      allows cell proliferation and differentiation when its expression oscillates but
      induces dormancy when its expression is sustained. After Hes1 expression is
      repressed, Ngn2 is expressed in a sustained manner, promoting neuronal
      differentiation. Thus, Ngn2 leads to the maintenance of neural stem/progenitor
      cells by inducing Dll1 oscillation when its expression oscillates but to neuronal
      differentiation when its expression is sustained. These results indicate that the
      different dynamics of Hes1 and Ngn2 lead to different outcomes.

PMID- 21716645
TI  - Interval timing deficits and abnormal cognitive development.

PMID- 21716646
TI  - Feasibility of imaging esophageal cancer with labeled somatostatin analogue.
AB  - Background. While the surface of a cell normally has some amount of somatostatin
      receptors, these receptors are overexpressed to a very high degree in multiple
      neoplastic diseases. No data exist for esophageal carcinoma. Purpose. To find out
      whether esophageal carcinoma could be imaged using somatostatin receptor
      scintigraphy. Material and Methods. 34 patients with esophageal lesions were
      prospectively examined by (99m)Tc-depreotide scintigraphy 2 and 4 hours after
      injection. Quantitative evaluation of (99m)Tc-depreotide uptake was performed
      around the lesion (T) and in healthy lung parenchyma (B). The relative uptake was
      calculated as T-B/B. Scintigraphy results were compared with histopathology from
      surgery or biopsy specimens from endoscopic ultrasonography. Results. 21 patients
      had esophageal cancer, and 13 lesions were benign. Visual assessment revealed
      positive (99m)Tc-depreotide uptake in 16 of the 21 cancers. The 13 patients
      without cancer had no depreotide uptake. The Mann-Whitney U test showed a
      statistically significant difference (P < .005) between (99m)Tc-depreotide uptake
      in malignant and benign lesions, for both the 2-hour and the 4-hour measurements.
      Conclusion. Scintigraphic examination with (99m)Tc-depreotide is feasible for
      imaging esophageal cancer, but the method is not suitable neither for screening
      or primary diagnosis, because of methods modest sensitivity. Our first results
      showed high specificity which should be used with caution, as the number of
      patients was relatively low. Further studies are needed to determine the role of
      the method.

PMID- 21716647
TI  - Microbial ecology and global health.

PMID- 21716648
TI  - Human motor neuron progenitor transplantation leads to endogenous neuronal
      sparing in 3 models of motor neuron loss.
AB  - Motor neuron loss is characteristic of many neurodegenerative disorders and
      results in rapid loss of muscle control, paralysis, and eventual death in severe
      cases. In order to investigate the neurotrophic effects of a motor neuron lineage
      graft, we transplanted human embryonic stem cell-derived motor neuron progenitors
      (hMNPs) and examined their histopathological effect in three animal models of
      motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA
      (Delta7SMN), ALS (SOD1 G93A), and spinal cord injury (SCI). The transplanted
      cells survived and differentiated in all models. In addition, we have also found
      that hMNPs secrete physiologically active growth factors in vivo, including NGF
      and NT-3, which significantly enhanced the number of spared endogenous neurons in
      all three animal models. The ability to maintain dying motor neurons by
      delivering motor neuron-specific neurotrophic support represents a powerful
      treatment strategy for diseases characterized by motor neuron loss.

PMID- 21716649
TI  - Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in
      vitro and in vivo.
AB  - The aims of the study are to explore the effect of ursolic acid (UA) on the
      growth of gastric cancer cell line BGC-803 and hepatocellular cancer cell H22
      xenograft and to understand the mechanism. UA inhibits growth of BGC-803 cells in
      vitro in dose-dependent and time-dependent manner. Treated with UA in vivo, tumor
      cells can be arrested to G0/G1 stage. The apoptotic rate was significantly
      increased in tumor cells treated with UA both in vitro and in vivo. DNA
      fragmentation was found in BGC-803 cells exposed to UA. UA activated caspase-3, 
      8, and -9 and down regulated expression of Bcl-2 in BGC-803 cells. The expression
      of caspase-3 and -8 was elevated in tumor cells from xenograft treated with UA.
      18F-FLT PET-CT imaging confirmed tumor model and UA effectiveness. Our results
      indicated that UA inhibits growth of tumor cells both in vitro and in vivo by
      decreasing proliferation of cells and inducing apoptosis.

PMID- 21716650
TI  - Examinations of tRNA Range of Motion Using Simulations of Cryo-EM Microscopy and
      X-Ray Data.
AB  - We examined tRNA flexibility using a combination of steered and unbiased
      molecular dynamics simulations. Using Maxwell's demon algorithm, molecular
      dynamics was used to steer X-ray structure data toward that from an alternative
      state obtained from cryogenic-electron microscopy density maps. Thus, we were
      able to fit X-ray structures of tRNA onto cryogenic-electron microscopy density
      maps for hybrid states of tRNA. Additionally, we employed both Maxwell's demon
      molecular dynamics simulations and unbiased simulation methods to identify
      possible ribosome-tRNA contact areas where the ribosome may discriminate tRNAs
      during translation. Herein, we collected >500 ns of simulation data to assess the
      global range of motion for tRNAs. Biased simulations can be used to steer between
      known conformational stop points, while unbiased simulations allow for a general
      testing of conformational space previously unexplored. The unbiased molecular
      dynamics data describes the global conformational changes of tRNA on a sub
      microsecond time scale for comparison with steered data. Additionally, the
      unbiased molecular dynamics data was used to identify putative contacts between
      tRNA and the ribosome during the accommodation step of translation. We found that
      the primary contact regions were H71 and H92 of the 50S subunit and ribosomal
      proteins L14 and L16.

PMID- 21716651
TI  - Phase I/II Clinical Trials Using Gene-Modified Adult Hematopoietic Stem Cells for
      HIV: Lessons Learnt.
AB  - Gene therapy for individuals infected with HIV has the potential to provide a
      once-only treatment that will act to reduce viral load, preserve the immune
      system, and mitigate cumulative toxicities associated with highly active
      antiretroviral therapy (HAART). The authors have been involved in two clinical
      trials (phase I and phase II) using gene-modified adult hematopoietic stem cells
      (HSCs), and these are discussed as prototypic trials within the general field of
      HSC gene therapy trials for HIV. Taken as a group these trials have shown (i) the
      safety of both the procedure and the anti-HIV agents themselves and (ii) the
      feasibility of the approach. They point to the requirement for (i) the ability to
      transduce and infuse as many as possible gene-containing HSC and/or (ii) high
      engraftment and in vivo expansion of these cells, (iii) potentially increased
      efficacy of the anti-HIV agent(s) and (iv) automation of the cell processing
      procedure.

PMID- 21716652
TI  - Real-time monitoring of neural differentiation of human mesenchymal stem cells by
      electric cell-substrate impedance sensing.
AB  - Stem cells are useful for cell replacement therapy. Stem cell differentiation
      must be monitored thoroughly and precisely prior to transplantation. In this
      study we evaluated the usefulness of electric cell-substrate impedance sensing
      (ECIS) for in vitro real-time monitoring of neural differentiation of human
      mesenchymal stem cells (hMSCs). We cultured hMSCs in neural differentiation media
      (NDM) for 6 days and examined the time-course of impedance changes with an ECIS
      array. We also monitored the expression of markers for neural differentiation,
      total cell count, and cell cycle profiles. Cellular expression of neuron and
      oligodendrocyte markers increased. The resistance value of cells cultured in NDM
      was automatically measured in real-time and found to increase much more slowly
      over time compared to cells cultured in non-differentiation media. The relatively
      slow resistance changes observed in differentiating MSCs were determined to be
      due to their lower growth capacity achieved by induction of cell cycle arrest in
      G0/G1. Overall results suggest that the relatively slow change in resistance
      values measured by ECIS method can be used as a parameter for slowly growing
      neural-differentiating cells. However, to enhance the competence of ECIS for in
      vitro real-time monitoring of neural differentiation of MSCs, more elaborate
      studies are needed.

PMID- 21716653
TI  - EI of the Phosphotransferase System of Escherichia coli: Mathematical Modeling
      Approach to Analysis of Its Kinetic Properties.
AB  - The mathematical model of the operation of the first enzyme of the Escherichia
      coli phosphotransferase system, EI, is proposed. Parameters of the kinetic model
      describing the operation of EI under different conditions are identified on the
      basis of a large amount of known experimental data. The verified model is
      employed to predict modes of operation of EI under both in vivo physiological
      conditions and in vitro nonphysiological conditions. The model predicts that
      under in vivo physiological conditions, the rate of phosphotransfer from EI to
      the second protein of the phosphotransferase system HPr by the dimer is much
      higher than by the monomer. A hypothesis is proposed on the basis of calculations
      that the transfer by a monomer plays a role in the regulation of chemotaxis. At
      submicromolar pyruvate concentration, the model predicts nonmonotonic dependence
      of the phosphotransfer rate on the substrate (PEP) concentration.

PMID- 21716654
TI  - Stem cell-based approaches for the treatment of diabetes.
AB  - The incidence of diabetes and the associated debilitating complications are
      increasing at an alarming rate worldwide. Current therapies for type 1 diabetes
      focus primarily on administration of exogenous insulin to help restore glucose
      homeostasis. However, such treatment rarely prevents the long-term complications
      of this serious metabolic disorder, including neuropathy, nephropathy,
      retinopathy, and cardiovascular disease. Whole pancreas or islet transplantations
      have enjoyed limited success in some individuals, but these approaches are
      hampered by the shortage of suitable donors and the burden of lifelong
      immunosuppression. Here, we review current approaches to differentiate nonislet
      cell types towards an islet-cell phenotype which may be used for larger-scale
      cell replacement strategies. In particular, the differentiation protocols used to
      direct embryonic stem cells, progenitor cells of both endocrine and nonendocrine
      origin, and induced pluripotent stem cells towards an islet-cell phenotype are
      discussed.

PMID- 21716655
TI  - Leptin in teleost fishes: an argument for comparative study.
AB  - All organisms face tradeoffs with regard to how limited energy resources should
      be invested. When is it most favorable to grow, to reproduce, how much lipid
      should be allocated to storage in preparation for a period of limited resources
      (e.g., winter), instead of being used for growth or maturation? These are a few
      of the high consequence fitness "decisions" that represent the balance between
      energy acquisition and allocation. Indeed, for animals to make favorable
      decisions about when to grow, eat, or reproduce, they must integrate signals
      among the systems responsible for energy acquisition, storage, and demand. We
      make the argument that leptin signaling is a likely candidate for an integrating
      system. Great progress has been made understanding the leptin system in mammals,
      however our understanding in fishes has been hampered by difficulty in cloning
      fish orthologs of mammalian proteins and (we assert), underutilization of the
      comparative approach.

PMID- 21716656
TI  - The 5-HT(2A) Receptor Antagonist M100907 Produces Antiparkinsonian Effects and
      Decreases Striatal Glutamate.
AB  - 5-HT plays a regulatory role in voluntary movements of the basal ganglia and has
      a major impact on disorders of the basal ganglia such as Parkinson's disease
      (PD). Clinical studies have suggested that 5-HT(2) receptor antagonists may be
      useful in the treatment of the motor symptoms of PD. We hypothesized that 5
      HT(2A) receptor antagonists may restore motor function by regulating
      glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) exhibited decreased performance on the beam
      walking apparatus. Peripheral administration of the 5-HT(2A) receptor antagonist
      M100907 improved performance of MPTP-treated mice on the beam-walking apparatus.
      In vivo microdialysis revealed an increase in striatal extracellular glutamate in
      MPTP-treated mice and local perfusion of M100907 into the dorsal striatum
      significantly decreased extracellular glutamate levels in saline and MPTP-treated
      mice. Our studies suggest that blockade of 5-HT(2A) receptors may represent a
      novel therapeutic target for the motor symptoms of PD.

PMID- 21716658
TI  - Production of beta-Glucosidase from a Newly Isolated Aspergillus Species Using
      Response Surface Methodology.
AB  - A newly isolated fungus Aspergillus niger SOI017 was shown to be a good producer
      of beta-glucosidase from all isolated fungal strains. Fermentation condition (pH,
      cellobiose concentration, yeast extract concentration, and ammonium sulfate
      concentration) was optimized for producing the enzyme in shake flask cultures.
      Response surface methodology was used to investigate the effects of 4
      fermentation parameters (yeast extract concentration, cellobiose concentration,
      ammonium sulfate concentration, and pH) on beta-glucosidase enzyme production.
      Production of beta-glucosidase was most sensitive to the culture medium,
      especially the nitrogen source yeast extract. The optimized medium for producing
      maximum beta-glucosidase specific activity consisted of 0.275% yeast extract,
      1.125% cellobiose, and 2.6% ammonium sulfate at a pH value of 3.

PMID- 21716657
TI  - The Role of the spv Genes in Salmonella Pathogenesis.
AB  - Salmonella strains cause three main types of diseases in people: gastroenteritis,
      enteric (typhoid) fever, and non-typhoid extra-intestinal disease with
      bacteremia. Genetic analysis indicates that each clinical syndrome requires
      distinct sets of virulence genes, and Salmonella isolates differ in their
      constellation of virulence traits. The spv locus is strongly associated with
      strains that cause non-typhoid bacteremia, but are not present in typhoid
      strains. The spv region contains three genes required for the virulence phenotype
      in mice: the positive transcriptional regulator spvR and two structural genes
      spvB and spvC. SpvB and SpvC are translocated into the host cell by the
      Salmonella pathogenicity island-2 type-three secretion system. SpvB prevents
      actin polymerization by ADP-ribosylation of actin monomers, while SpvC has
      phosphothreonine lyase activity and has been shown to inhibit MAP kinase
      signaling. The exact mechanisms by which SpvB and SpvC act in concert to enhance
      virulence are still unclear. SpvB exhibits a cytotoxic effect on host cells and
      is required for delayed cell death by apoptosis following intracellular
      infection. Strains isolated from systemic infections of immune compromised
      patients, particularly HIV patients, usually carry the spv locus, strongly
      suggesting that CD4 T cells are required to control disease due to Salmonella
      that are spv positive. This association is not seen with typhoid fever,
      indicating that the pathogenesis and immunology of typhoid have fundamental
      differences from the syndrome of non-typhoid bacteremia.

PMID- 21716659
TI  - Identification of genes regulating gene targeting by a high-throughput screening
      approach.
AB  - Homologous gene targeting (HGT) is a precise but inefficient process for genome
      engineering. Several methods for increasing its efficiency have been developed,
      including the use of rare cutting endonucleases. However, there is still room for
      improvement, as even nuclease-induced HGT may vary in efficiency as a function of
      the nuclease, target site, and cell type considered. We have developed a high
      throughput screening assay for the identification of factors stimulating
      meganuclease-induced HGT. We used this assay to explore a collection of siRNAs
      targeting 19,121 human genes. At the end of secondary screening, we had
      identified 64 genes for which knockdown affected nuclease-induced HGT. Two of the
      strongest candidates were characterized further. We showed that siRNAs directed
      against the ATF7IP gene, encoding a protein involved in chromatin remodeling,
      stimulated HGT by a factor of three to eight, at various loci and in different
      cell types. This method thus led to the identification of a number of genes, the
      manipulation of which might increase rates of targeted recombination.

PMID- 21716660
TI  - Immune Reactions following Cord Blood Transplantations in Adults.
AB  - Cord blood transplantation (CBT) is an attractive alternative therapy in adult
      patients with advanced hematological malignancies in whom matched donors are
      unavailable. However, the risk of complications, especially infections, post-CBT
      increases the mortality rates in these patients. Although the incidence of acute
      and chronic graft versus host disease (GVHD) post-CBT is lower than that
      following bone marrow transplantation and peripheral blood stem cell
      transplantation (SCT), the additional immunosuppressive therapy required to treat
      it could increase the mortality in these patients. Further, chronic GVHD
      following CBT is milder and responds better to treatment than that occurring
      after bone marrow transplants. Unlike bone marrow transplantation, the onset of
      GVHD is a positive prognostic indicator of overall survival in patients receiving
      CBT, due to the graft versus malignancy (GVM) effect. This paper focuses on the
      immune reactions following CBT and aims to elucidate a management strategy for
      acute and chronic GVHD.

PMID- 21716661
TI  - Next-generation sequencing of microRNAs for breast cancer detection.
AB  - It is reported that different microRNA (miRNA) profiles can be detected in the
      blood of cancer patients. We investigated that whether the key serum miRNAs could
      discriminate patients with and without breast cancer. This study was divided into
      three parts: (1) miRNA marker discovery using SOLiD sequencing-based miRNA
      profiling on cancerous and adjacent noncancerous breast tissue of one breast
      cancer patient; (2) marker selection and validation by real-time PCR on a small
      set of serum; (3) gene ontology analysis of the key miRNA target genes. Of genome
      wide tissue miRNA expression analysis, five miRNAs were found to be altered more
      than fivefold by SOLiD sequencing (i.e., miR-29a, miR-23a, miR-23b, miR-192, and
      miR-21). All the five miRNAs were validated on the 20 breast cancer patients and
      20 controls. miR-29a and miR-21 were significantly increased in the serum of
      breast cancer patients (P < .05). Gene ontology analysis of the target genes
      revealed enrichment for special biological process categories, that is, signal
      transduction, development, apoptosis, cell proliferation, and cell adhesion.
      SOLiD sequencing provides a promising method for cancer-related miRNA profiling.
      Serum miRNAs may be useful biomarkers for breast cancer detection.

PMID- 21716662
TI  - A Dog with Pseudo-Addison Disease Associated with Trichuris vulpis Infection.
AB  - A female Rottweiler dog was presented with a history of intermittent vomiting and
      diarrhoea, dysorexia, weakness, and weight loss. Haemocytometry and biochemistry
      values were within normal ranges except for electrolyte analyses, that
      demonstrated hyponatremia and hyperkalemia with a decreased sodium/potassium
      ratio. A diagnosis of hypoadrenocorticism was suspected. Basal and post-ACTH
      stimulation cortisolemia were within the normal values. Electrocardiography was
      normal, and thoracic radiography showed no significant modifications. On
      abdominal ultrasonography, adrenal glands appeared normal, while the bowel was
      distended, and several thin linear hyperechoic objects floating in the lumen were
      observed. Two adult female whipworms (Trichuris vulpis) were collected following
      bowel irrigation. Anthelmintic treatment against the parasite was curative.

PMID- 21716663
TI  - Mild Hypothermia Attenuates Intercellular Adhesion Molecule-1 Induction via
      Activation of Extracellular Signal-Regulated Kinase-1/2 in a Focal Cerebral
      Ischemia Model.
AB  - Intercellular adhesion molecule-1 (ICAM-1) in cerebral vascular endothelium
      induced by ischemic insult triggers leukocyte infiltration and inflammatory
      reaction. We investigated the mechanism of hypothermic suppression of ICAM-1 in a
      model of focal cerebral ischemia. Rats underwent 2 hours of middle cerebral
      artery occlusion and were kept at 37 degrees C or 33 degrees C during occlusion
      and rewarmed to normal temperature immediately after reperfusion. Under
      hypothermic condition, robust activation of extracellular signal-regulated kinase
      1/2 (ERK1/2) was observed in vascular endothelium of ischemic brain. Hypothermic
      suppression of ICAM-1 was reversed by ERK1/2 inhibition. Phosphorylation of
      signal transducer and activator of transcription 3 (STAT3) in ischemic vessel was
      attenuated by hypothermia. STAT3 inhibitor suppressed ICAM-1 production induced
      by stroke. ERK1/2 inhibition enhanced phosphorylation and DNA binding activity of
      STAT3 in hypothermic condition. In this study, we demonstrated that hypothermic
      suppression of ICAM-1 induction is mediated by enhanced ERK1/2 activation and
      subsequent attenuation of STAT3 action.

PMID- 21716664
TI  - The implications of the working memory model for the evolution of modern
      cognition.
AB  - What distinguishes the cognition of biologically modern humans from that of more
      archaic populations such as Neandertals? The norm in paleoanthropology has been
      to emphasize the role of language and symbolism. But the modern mind is more than
      just an archaic mind enhanced by symbol use. It also possesses an important
      problem solving and planning component. In cognitive neuroscience these advanced
      planning abilities have been extensively investigated through a formal model
      known as working memory. The working memory model is now well-enough established
      to provide a powerful lens through which paleoanthropologists can view the fossil
      and archaeological records. The challenge is methodological. The following essay
      reviews the controversial hypothesis that a recent enhancement of working memory
      capacity was the final piece in the evolution of modern cognition.

PMID- 21716665
TI  - Derivation of two new human embryonic stem cell lines from nonviable human
      embryos.
AB  - We report the derivation and characterization of two new human embryonic stem
      cells (hESC) lines (CU1 and CU2) from embryos with an irreversible loss of
      integrated organismic function. In addition, we analyzed retrospective data of
      morphological progression from embryonic day (ED) 5 to ED6 for 2480 embryos not
      suitable for clinical use to assess grading criteria indicative of loss of
      viability on ED5. Our analysis indicated that a large proportion of in vitro
      fertilization (IVF) embryos not suitable for clinical use could be used for hESC
      derivation. Based on these combined findings, we propose that criteria commonly
      used in IVF clinics to determine optimal embryos for uterine transfer can be
      employed to predict the potential for hESC derivation from poor quality embryos
      without the destruction of vital human embryos.

PMID- 21716666
TI  - Pathogen recognition by the long pentraxin PTX3.
AB  - Innate immunity represents the first line of defence against pathogens and plays
      key roles in activation and orientation of the adaptive immune response. The
      innate immune system comprises both a cellular and a humoral arm. Components of
      the humoral arm include soluble pattern recognition molecules (PRMs) that
      recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune
      response in coordination with the cellular arm, therefore acting as functional
      ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that
      is produced at sites of infection and inflammation by both somatic and immune
      cells. Gene targeting of this evolutionarily conserved protein has revealed a
      nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts
      important functions at the cross-road between innate immunity, inflammation, and
      female fertility. Here, we review the studies on PTX3, with emphasis on pathogen
      recognition and cross-talk with other components of the innate immune system.

PMID- 21716667
TI  - Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell
      exhaustion syndromes?
AB  - One of the most important and complex diseases of modern society is metabolic
      syndrome. This syndrome has not been completely understood, and therefore an
      effective treatment is not available yet. We propose a possible stem cell
      mechanism involved in the development of metabolic syndrome. This way of thinking
      lets us consider also other significant pathologies that could have similar
      etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All
      these clinical situations could be the consequence of a progressive and
      persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES
      would be an irreversible loss of the effective regenerative mesenchymal stem
      cells (MSCs) pools. In this way, the normal repairing capacities of the organism
      could become inefficient. Our point of view could open the possibility for a new
      strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria,
      and even aging: stem cell therapies.

PMID- 21716668
TI  - Protein expression of mesenchymal stem cells after transfection of pcDNA3.1-
      hVEGF165 by ultrasound-targeted microbubble destruction.
AB  - Ultrasound-targeted microbubble destruction (UTMD) has been proposed as a new
      technique for organ-specific gene transfer and drug delivery. This study was
      performed to investigate the effect of UTMD on marrow mesenchymal stem cells
      (MSCs) transfected with pcDNA3.1--hVEGF165.pcDNA3.1--hVEGF165 were transfected
      into the third passage of MSCs, with or without UTMD under different ultrasound
      conditions. Protein expression was quantified by hVEGF165-ELISA kit after
      transfection for 24, 48, and 72 hours. UTMD-mediated transfection of MSCs yielded
      a significant protein expression. UTMD of mechanic index (MI) 0.6 for 90 seconds
      led to the highest level of protein expression.

PMID- 21716669
TI  - DMSO-Free Programmed Cryopreservation of Fully Dissociated and Adherent Human
      Induced Pluripotent Stem Cells.
AB  - THREE MODES FOR CRYOPRESERVATION (CP) OF HUMAN IPSC CELLS HAVE BEEN COMPARED:
      STD: standard CP of small clumps with 10% of CPA in cryovials, ACC: dissociation
      of the cells with Accutase and freezing in cryovials, and PLT: programmed
      freezing of adherent cells in plastic multiwell dishes in a programmable freezer
      using one- and multistep cooling protocols. Four CPAs were tesetd: dimethyl
      sulfoxide (DMSO), ethylene glycol (EG), propylene glycol (PG), and glycerol
      (GLY). The cells in ACC and PLT were frozen and recovered after thawing in the
      presence of a ROCK inhibitor Y-27632 (RI). EG was less toxic w/o CP
      cryopreservation than DMSO and allowed much better maintenance of pluripotency
      after CP than PG or GLY. The cells were cryopreserved very efficiently as
      adherent cultures (+RI) in plates (5-6-fold higher than STD) using EG and a 6
      step freezing protocol. Recovery under these conditions is comparable or even
      higher than ACC+RI. Conclusions. Maintenance of cell-substratum adherence is a
      favorable environment that mitigates freezing and thawing stresses
      (ComfortFreeze((r)) concept developed by CELLTRONIX). CP of cells directly in
      plates in ready-to-go after thawing format for HT/HC screening can be beneficial
      in many SC-related scientific and commercial applications such as drug discovery
      and toxicity tests.

PMID- 21716670
TI  - Role of common-gamma chain cytokines in NK cell development and function:
      perspectives for immunotherapy.
AB  - NK cells are components of the innate immunity system and play an important role
      as a first-line defense mechanism against viral infections and in tumor immune
      surveillance. Their development and their functional activities are controlled by
      several factors among which cytokines sharing the usage of the common cytokine
      receptor gamma chain play a pivotal role. In particular, IL-2, IL-7, IL-15, and
      IL-21 are the members of this family predominantly involved in NK cell biology.
      In this paper, we will address their role in NK cell ontogeny, regulation of
      functional activities, development of specialized cell subsets, and acquisition
      of memory-like functions. Finally, the potential application of these cytokines
      as recombinant molecules to NK cell-based immunotherapy approaches will be
      discussed.

PMID- 21716671
TI  - A symphony of regulations centered on p63 to control development of ectoderm
      derived structures.
AB  - The p53-related transcription factor p63 is critically important for basic
      cellular functions during development of the ectoderm and derived structure and
      tissues, including skin, limb, palate, and hair. On the one side, p63 is required
      to sustain the proliferation of keratinocyte progenitors, while on the other side
      it is required for cell stratification, commitment to differentiate, cell
      adhesion, and epithelial-mesenchymal signaling. Molecules that are components or
      regulators of the p63 pathway(s) are rapidly being identified, and it comes with
      no surprise that alterations in the p63 pathway lead to congenital conditions in
      which the skin and other ectoderm-derived structures are affected. In this paper,
      we summarize the current knowledge of the molecular and cellular regulations
      centered on p63, derived from the comprehension of p63-linked human diseases and
      the corresponding animal models, as well as from cellular models and high
      throughput molecular approaches. We point out common themes and features, that
      allow to speculate on the possible role of p63 downstream events and their
      potential exploitation in future attempts to correct the congenital defect in
      preclinical studies.

PMID- 21716672
TI  - Sparse logistic regression for diagnosis of liver fibrosis in rat by using SCAD
      penalized likelihood.
AB  - The objective of the present study is to find out the quantitative relationship
      between progression of liver fibrosis and the levels of certain serum markers
      using mathematic model. We provide the sparse logistic regression by using
      smoothly clipped absolute deviation (SCAD) penalized function to diagnose the
      liver fibrosis in rats. Not only does it give a sparse solution with high
      accuracy, it also provides the users with the precise probabilities of
      classification with the class information. In the simulative case and the
      experiment case, the proposed method is comparable to the stepwise linear
      discriminant analysis (SLDA) and the sparse logistic regression with least
      absolute shrinkage and selection operator (LASSO) penalty, by using receiver
      operating characteristic (ROC) with bayesian bootstrap estimating area under the
      curve (AUC) diagnostic sensitivity for selected variable. Results show that the
      new approach provides a good correlation between the serum marker levels and the
      liver fibrosis induced by thioacetamide (TAA) in rats. Meanwhile, this approach
      might also be used in predicting the development of liver cirrhosis.

PMID- 21716673
TI  - Physiologically based pharmacokinetic modeling: methodology, applications, and
      limitations with a focus on its role in pediatric drug development.
AB  - The concept of physiologically based pharmacokinetic (PBPK) modeling was
      introduced years ago, but it has not been practiced significantly. However,
      interest in and implementation of this modeling technique have grown, as
      evidenced by the increased number of publications in this field. This paper
      demonstrates briefly the methodology, applications, and limitations of PBPK
      modeling with special attention given to discuss the use of PBPK models in
      pediatric drug development and some examples described in detail. Although PBPK
      models do have some limitations, the potential benefit from PBPK modeling
      technique is huge. PBPK models can be applied to investigate drug
      pharmacokinetics under different physiological and pathological conditions or in
      different age groups, to support decision-making during drug discovery, to
      provide, perhaps most important, data that can save time and resources,
      especially in early drug development phases and in pediatric clinical trials, and
      potentially to help clinical trials become more "confirmatory" rather than
      "exploratory".

PMID- 21716674
TI  - Vanadium inhalation in a mouse model for the understanding of air-suspended
      particle systemic repercussion.
AB  - There is an increased concern about the health effects that air-suspended
      particles have on human health which have been dissected in animal models. Using
      CD-1 mouse, we explore the effects that vanadium inhalation produce in different
      tissues and organs. Our findings support the systemic effects of air pollution.
      In this paper, we describe our findings in different organs in our conditions and
      contrast our results with the literature.

PMID- 21716675
TI  - Anticonvulsant Activity of Extracts of Plectranthus barbatus Leaves in Mice.
AB  - Plectranthus barbatus is a medicinal plant used to treat a wide range of
      disorders including seizure. However, the anticonvulsant activity of this plant
      has not been studied in depth. We therefore sought to evaluate the anticonvulsant
      activity of a hydroalcoholic extract of P. barbatus leaves on seizures induced by
      strychnine sulphate (2.0 mg/kg) and pilocarpine (600 mg/kg) in mice. The extract
      was administered orally at 1, 10, 30, and 100 mg/kg. We report that the P.
      barbatus extract had marked anticonvulsant activity against strychnine-induced
      convulsions, but was quite ineffective against pilocarpine-induced convulsions.
      Further experiments will be required to identify the active molecules(s) and
      their mechanism(s) of action.

PMID- 21716676
TI  - Power spectral analyses of index finger skin blood perfusion in carpal tunnel
      syndrome and diabetic polyneuropathy.
AB  - The main purpose of this study was to investigate the applicability of frequency
      domain analysis on laser Doppler flowmetry (LDF) data recorded from the index
      fingers of patients with carpal tunnel syndrome (CTS) and diabetic polyneuropathy
      (DPN). Patients with numbness of the palm were recruited and grouped according to
      the results of electrophysiological examinations into 2*2 groups by the existence
      or nonexistence of CTS and/or DPN. Skin blood perfusion was recorded by LDF in
      both the neutral position and the maximally flexed position (the Phalen test). S
      transformation was utilized to decompose the recorded data into frequency bands,
      and the relative band power and power dispersion were calculated. Analysis of
      variance was used to test the effects of DPN, CTS, and the Phalen test results.
      The results showed that (1) DPN decreased the absolute power and the relative
      power in some frequency bands in both positions and CTS increased the power
      dispersion of some frequency bands only during the Phalen test and (2) there was
      no difference in the LDF results between patients with positive or negative
      Phalen test results.

PMID- 21716677
TI  - Copaiba Oil: An Alternative to Development of New Drugs against Leishmaniasis.
AB  - Leishmaniasis is a neglected disease that is increasing globally at an alarming
      rate. Glucantime has been the therapy of choice for more than 50 years. A recent
      study reported the antileishmanial activity of copaiba oil against Leishmania
      amazonensis. These results led us to investigate morphological and
      ultrastructural changes in L. amazonensis treated with copaiba oil, using
      electron microscopy and flow cytometry to assess specific organelles as targets
      for copaiba oil. In the promastigote and axenic amastigote forms, this copaiba
      oil caused notable morphological and ultrastructural changes, including extensive
      mitochondrial damage and denaturation of the plasma membrane. Copaiba oil
      treatment also induced a decrease in Rh123 fluorescence, suggesting interference
      with the mitochondrial membrane potential and loss of cell viability with an
      increase in plasma membrane permeability, as observed by flow cytometry after
      staining with propidium iodide. In conclusion, copaiba oil could be exploited for
      the development of new antileishmanial drugs.

PMID- 21716678
TI  - Effects of encapsulated propolis on blood glycemic control, lipid metabolism, and
      insulin resistance in type 2 diabetes mellitus rats.
AB  - The present study investigates the encapsulated propolis on blood glycemic
      control, lipid metabolism, and insulin resistance in type 2 diabetes mellitus
      (T2DM) rats. The animal characteristics and biological assays of body weight,
      fasting blood glucose (FBG), fasting serum insulin (FINS), insulin act index
      (IAI), triglycerides (TG), total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were
      measured and euglycemic hyperinsulinemic glucose clamp technique were used to
      determine these effects. Our findings show that oral administration of
      encapsulated propolis can significantly inhibit the increasing of FBG and TG in
      T2DM rats and can improve IAI and M value in euglycemic hyperinsulinemic clamp
      experiment. There was no significant effects on body weight, TC, HDL-C, and LDL-C
      in T2DM rats treated with encapsulated propolis. In conclusion, the results
      indicate that encapsulated propolis can control blood glucose, modulate lipid
      metabolism, and improve the insulin sensitivity in T2DM rats.

PMID- 21716679
TI  - Antihypertriglyceridemia and anti-inflammatory activities of monascus-fermented
      dioscorea in streptozotocin-induced diabetic rats.
AB  - The rice fermented by Monascus, called red mold rice (RMR), and has a long
      tradition in East Asia as a dietary staple. Monascus-fermented dioscorea called
      red mold dioscorea (RMD) contains various metabolites to perform the ability of
      reducing oxidative stress and anti-inflammatory response. We used Wistar rats and
      induced diabetes by injecting streptozotocin (STZ, 65 mg/kg i.p.). RMD was
      administered daily starting six weeks after disease onset. Throughout the
      experimental period, significantly (P < .05) lowered plasma glucose,
      triglyceride, cholesterol, free fatty acid and low density lipoprotein levels
      were observed in the RMD-treated groups. The RMD-treated diabetic rats showed
      higher activities of glutathione disulfide reductase, glutathione reductase,
      catalase and superoxide dismutase (P < .05) in the pancreas compared with the
      diabetic control rats. RMD also inhibited diabetes-induced elevation in the
      levels of interleukin (IL)-1beta, IL-6, interferon-gamma and tumor necrosis
      factor-alpha. Pancreatic beta-cells damaged by STZ in the RMD supplemented groups
      were ameliorated. The results of this study clearly demonstrated that RMD
      possesses several treatment-oriented properties, including the control of
      hyperglycemia, antioxidant effects, pancreatic beta-cell protection and anti
      inflammatory effects. Considering these observations, it appears that RMD may be
      a useful supplement to delay the development of diabetes and its complications.

PMID- 21716680
TI  - Characteristics of the Aragonitic Layer in Adult Oyster Shells, Crassostrea
      gigas: Structural Study of Myostracum including the Adductor Muscle Scar.
AB  - Myostracum, which is connected from the umbo to the edge of a scar, is not a
      single layer composed of prismatic layers, but a hierarchically complex
      multilayered shape composed of minerals and an organic matrix. Through the
      analysis of the secondary structure, the results revealed that a beta
      antiparallel structure was predominant in the mineral phase interface between the
      myostracum (aragonite) and bottom folia (calcite). After the complete
      decalcification and deproteinization, the membrane obtained from the interface
      between the myostracum buried in upper folia, and the bottom folia was identified
      as chitin. The transitional zone in the interface between the adductor muscle
      scar and folia are verified. The myostracum disappeared at the edge of the scar
      of the posterior side. From this study, the entire structure of the myostracum
      from the adult oyster shell of Crassostrea gigas could be proposed.

PMID- 21716681
TI  - The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA-10 Mouse Leydig
      Tumor Cells.
AB  - Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS). We
      have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell
      and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible
      that cordycepin is the main component in CS modulating Leydig cell functions.
      Thus, our aim was to investigate the steroidogenic and apoptotic effects with
      potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results
      showed that cordycepin significantly stimulated progesterone production in dose-
      and time-dependent manners. Adenosine receptor (AR) subtype agonists were further
      used to treat MA-10 cells, showing that A(1), A( 2A ), A( 2B ), and A(3), AR
      agonists could stimulate progesterone production. However, StAR promoter activity
      and protein expression remained of no difference among all cordycepin treatments,
      suggesting that cordycepin might activate AR, but not stimulated StAR protein to
      regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce
      apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced
      cell death in a dose-dependent manner, and four AR subtype antagonists could all
      rescue cell death under cordycepin treatment in MA-10 cells. In conclusion,
      cordycepin could activate adenosine subtype receptors and simultaneously induce
      steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

PMID- 21716682
TI  - Effect of Supplementation of Tanshinone IIA and Sodium Tanshinone IIA Sulfonate
      on the Anticancer Effect of Epirubicin: An In Vitro Study.
AB  - Tanshinone IIA (Tan IIA) and sodium tanshinone IIA sulfonate (STS) were found to
      have protective effects on cardiomyocyte against adriamycin-induced damage and
      may be used clinically. It is unclear whether the supplementation of STS or Tan
      IIA would affect the anticancer activity of anthracycline. To evaluate the effect
      of Tan IIA or STS on the anticancer of epirubicin, the cell viability, apoptosis,
      Akt expression, and uptake of epirubicin after supplementation of Tan IIA or STS
      in the epirubicin-treated BT-20 cells were measured and compared. Tan IIA
      inhibited BT-20 cell growth and induced apoptosis in a time- and dose-dependent
      manner. When Tan IIA was used with epirubicin, an increase of BT-20 cells
      apoptosis was accompanied by the decreasing phosphorylation of Akt. STS had no
      effect on the cell viability of BT-20 cells. However, when used with epirubicin,
      STS decreased the epirubicin-induced cytotoxicity and apoptosis in BT-20 cells.
      The antagonistic effect of STS on epirubicin-induced cytotoxicity in BT-20 cells
      occurred concomitantly with the reduced epirubicin uptake and the increased
      phosphorylation of Akt. STS decreased the uptake of epirubicin in BT-20 cells and
      blocked epirubicin-induced apoptosis through activation of Akt.

PMID- 21716683
TI  - Isolation and Characterization of a Phosphate-Solubilizing Halophilic Bacterium
      Kushneria sp. YCWA18 from Daqiao Saltern on the Coast of Yellow Sea of China.
AB  - Phosphate-solubilizing bacteria (PSB) function in soil phosphorus cycle,
      increasing the bioavailability of soil phosphorus for plants. Isolation and
      application of salt-tolerant or halophilic PSB will facilitate the development of
      saline-alkali soil-based agriculture. A moderately halophilic bacterium was
      isolated from the sediment of Daqiao saltern on the eastern coast of China, which
      also performs phosphate-solubilizing ability. The bacterium was assigned to genus
      Kushneria according to its 16S rRNA gene sequence, and accordingly named as
      Kushneria sp. YCWA18. The fastest growth was observed when the culturing
      temperature was 28 degrees C and the concentration of NaCl was 6% (w/v). It was
      founds that the bacterium can survive at a concentration of NaCl up to 20%. At
      the optimum condition, the bacterium solubilized 283.16 MUg/mL phosphorus in 11
      days after being inoculated in 200 mL Ca(3)(PO(4))(2) containing liquid medium,
      and 47.52 MUg/mL phosphorus in 8 days after being inoculated in 200 mL lecithin
      containing liquid medium. The growth of the bacterium was concomitant with a
      significant decrease of acidity of the medium.

PMID- 21716684
TI  - Cardiac resynchronization therapy in the cardiorenal syndrome.
AB  - The cardiorenal syndrome (CRS) is a complex clinical syndrome in which
      dysfunction of either the heart or the kidneys affects the functioning of the
      other organ system. Many therapies used in heart failure have further detrimental
      effects on renal function. Cardiac resynchronization therapy (CRT) is a
      relatively new form of device therapy that reduces morbidity and mortality in
      patients with heart failure. This review will discuss the effects of CRT on renal
      function in patients with CRS, the impact of baseline renal function on response
      to CRT, and potential risks associated with CRT in this unique population.

PMID- 21716685
TI  - In Vitro Antiplasmodial Activity of Sesquiterpene Lactones from Ambrosia
      tenuifolia.
AB  - The in vitro antiplasmodial activity of Ambrosia tenuifolia organic extract and
      its isolated sesquiterpene lactones, psilostachyin and peruvin, has been
      evaluated against Plasmodium falciparum F32 and W2 strains. The cytotoxicity of
      both compounds was determined on lymphoid cells, and their corresponding
      selectivity indexes (SIs) were calculated. Peruvin was the most active compound
      on F32 strain of P. falciparum with a 50% inhibitory concentration value (IC(50))
      of 0.3 MUg/mL (1.1 MUM) whereas psilostachyin showed activity on both strains
      (IC(50) = 0.6 (2.1 MUM) and 1.8 MUg/mL (6.4 MUM)). Fifty percent cytotoxic
      concentration (CC(50)) values (48 h) were 6.8 MUg/mL (24.3 MUM) and 10.0 MUg/mL
      (37.9 MUM) for psilostachyin and peruvin, respectively.

PMID- 21716686
TI  - Free flap blood flow evaluated using two-dimensional laser speckle flowgraphy.
AB  - Objective. We investigated the efficiency of laser speckle flowgraphy for
      evaluating blood flow in free flaps used for plastic surgery. Methods. We
      measured blood flow using a visual laser meter capable of providing two
      dimensional color graphic representations of flow distribution for a given area
      using a dynamic laser speckle effect. Using laser speckle flowgraphy, we examined
      the blood flow of 20 free flaps applied following the excision of head and neck
      tumors. Results. After anastomosis of the feeding and draining blood vessels and
      sewing the flap, musculocutaneous (MC) flaps showed significantly lower blood
      flow than jejunal or omental flaps (P < .05). The ratio of blood flow decrease
      from the edge to the center was significantly greater in MC flaps than in jejunal
      or omental flaps (P < .001). Conclusion. Laser speckle flowgraphy is useful for
      the perioperative measurement of blood flow in free flaps used in plastic
      surgery. This method is a highly useful, practical, and reliable tool for
      assessing cutaneous blood flow and is expected to be applicable to several
      clinical fields.

PMID- 21716687
TI  - Toxicity and neuropharmacological effects of elenine.
AB  - Elenine is the aglycone of elenoside, a cytotoxic arylnaphthalene lignan (NSC
      644013-W/1) derived from Justicia hyssopifolia. (Family: Acanthaceae). Elenoside
      is a beta-D-glucoside, with a similar chemical structure to etoposide, exhibiting
      central depressant activity. In the present study, elenine was given to mice and
      rats at doses of 10, 20, and 40 mg/kg. Acute toxicity (24 h) and general
      behaviour in mice was studied as well as its effects on muscular relaxant
      activity, locomotor activity (Varimex test), and the open-field test and were
      compared with 10 mg/kg of chlorpromazine. Elenine produced a reduction in the
      permanence time in muscular relaxant activity (traction test). Spontaneous
      activity was lower in the Varimex test. The ambulation and rearing were lower
      compared with the control group, and an increase in boluses was observed in the
      open-field test. Thus, it can be concluded that elenine has central sedative
      effects at lower doses than those used with elenoside and has a possible
      application in conditions of anxiety.

PMID- 21716688
TI  - Tranexamic Acid treatment of life-threatening hematuria in polycystic kidney
      disease.
AB  - A 41-year-old woman with autosomal dominant polycystic kidney disease had chronic
      kidney disease class IV. She presented 10 days postpartum with a 4-day history of
      severe hematuria, left flank pain, and anemia, hemoglobin 62 g/L. CT scan showed
      massively enlarged kidneys with multiple cysts; several cysts bilaterally had
      high attenuation consistent with hemorrhage. Hematuria persisted over several
      days despite intensive conservative measures that included vitamin K1, 4 units of
      plasma, transfusion of 10 units of packed RBCs, Darbopoeitin, and DDAVP.
      Antifibrinolytic therapy was given with tranexamic acid 1000 mg p.o. t.i.d for
      one day then OD. The hematuria stopped within 24 hours and did not recur after
      tranexamic acid therapy ended. Over the next 4 years there were 3
      hospitalizations each with severe gross hematuria requiring blood transfusion for
      acute anemia. The hematuria responded well to further treatment with tranexamic
      acid. Tranexamic acid produces antifibrinolytic effects via complex interactions
      with plasminogen, displacing plasminogen from the fibrin surface. Chronic renal
      impairment is considered a relative contraindication to use of tranexamic acid
      due to reports of ureteric clots and acute renal failure from cortical necrosis.
      We conclude that tranexamic acid can be used safely in some patients with CKD and
      polycystic kidney disease to treat severe hematuria.

PMID- 21716689
TI  - External jugular vein aneurysm presenting as a cervical mass.
AB  - Venous aneurysms are rare causes of neck mass. Among neck veins, aneurysms of the
      external jugular vein are extremely uncommon. We present a case of a woman with a
      history of prior internal jugular vein catheterization who presented at a rural
      primary health care unit with a nontender progressively enlarging swelling in the
      right supraclavicular region. B-mode and Doppler ultrasound examination revealed
      a saccular dilatation of the external jugular vein, suggesting a posttraumatic
      venous aneurysm. Saccular aneurysms of the external jugular vein are uncommon and
      only rarely lead to serious complications. Access to ultrasound examination can
      allow early detection of this entity.

PMID- 21716690
TI  - Use of percutaneous ethanol injection therapy for recurrent secondary
      hyperparathyroidism after subtotal parathyroidectomy.
AB  - We evaluated the efficacy of percutaneous ethanol injection therapy (PEIT) as a
      therapeutic option for recurrence of secondary hyperparathyroidism after subtotal
      parathyroidectomy in ESRD patients. Six patients underwent PEIT. A mean of 1.3 +/
      0.8 ethanol injections was performed. Nodular volume was 1.5 +/- 1.7 cm(3), and
      2.8 +/- 2.8 cm(3) of ethanol was injected per patient. After ethanol injection
      PTH decreased significantly (1897 +/- 754 to 549 +/- 863 pg/mL (P < .01)). There
      was also a reduction in serum calcium, phosphorus and calcium-phosphorus product.
      A positive and significant correlation was found between nodular volume with
      ethanol injected and time from parathyroidectomy. Only one patient required
      hospitalization due to severe hypocalcaemia. In other two cases, local discomfort
      and temporary mild dysphonia were registered. PEIT is an effective treatment to
      control recurrences of secondary hyperparathyroidism postsubtotal
      parathyroidectomy.

PMID- 21716691
TI  - Modulation and Interaction of Immune-Associated Parameters with Antioxidant in
      the Immunocytes of Crab Scylla paramamosain Challenged with Lipopolysaccharides.
AB  - Invertebrates are dependent on cellular and humoral immune defences against
      microbial infection. Scylla paramamosain is an important commercial species, but
      the fundamental knowledge on its immune defense related to the antioxidant and
      immune-associated reactions is still lacking. The study was to differentiate the
      responses of immune-associated parameters of haemolymph components in S.
      paramamosain when challenged with bacterial lipopolysaccharides (LPSs). The
      immunostimulating effects of LPS in crab by triggering various immune parameters
      (phagocytosis, lysozyme, antibacterial activity, phenoloxidase, and the
      generation of superoxide and nitric oxide) were investigated. Results showed that
      the generation of free radicals, phenoloxidase, lysozyme and antibacterial
      activities was significantly increased through the exposure periods. Conversely,
      total hemocyte count and lysosomal membrane stability decreased significantly as
      the exposure period extended to 96 h. The relationship between the antioxidant
      enzymes and immune reactions due to LPS was highly significant. In addition, ROS
      production was positively correlated with antioxidant showing immediate response
      of antioxidant defense to the oxyradicals generated. Overall, the study indicated
      that nonspecific immune components in hemocytes of crab showed active response to
      the LPS stimulation, and their responses suggested that many immune-associated
      parameters could be modulated and interrelated with the influence of antioxidants
      in crustaceans.

PMID- 21716692
TI  - A model analysis of tensile stress in the toadfish vestibular membranes.
AB  - Background. A theoretical model analysis of stress in the vestibular membranes
      has identified a geometrical stress factor incorporating shape, size, and
      thickness that can be used to assess peak stress in the various chambers.
      Methods. Using published measurements of the toadfish vestibular membranes made
      during surgery, the geometrical stress factor can be evaluated for each chamber
      based on the model. Results. The mean geometrical stress factor is calculated to
      be the lowest in the semicircular canal (4.4), intermediate in the ampulla (6.0),
      and the highest in the utricle (17.4). Conclusions. The model predicts that
      substantial hoop stress disparities exist in the toadfish vestibular labyrinth.
      Stress is least in the semicircular canal, which therefore appears to be the
      structure with greatest stability. The utricle is found to be the most stress
      prone structure in the vestibular labyrinth and therefore appears to be the
      chamber most vulnerable to distention and potential modification.

PMID- 21716693
TI  - Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE
      Inhibitory Activities.
AB  - Considering the importance of diet in prevention of oxidative stress-related
      diseases including hypertension, this study was undertaken to evaluate the in
      vitro antioxidant and ACE inhibitory activities of selected culinary-medicinal
      mushrooms extracted by boiling in water for 30 min. Antioxidant capacity was
      measured using the following assays: DPPH free radical scavenging activity, beta
      carotene bleaching, inhibition of lipid peroxidation, reducing power ability, and
      cupric ion reducing antioxidant capacity (CUPRAC). Antioxidant potential of each
      mushroom species was calculated based on the average percentages relative to
      quercetin and summarized as Antioxidant Index (AI). Ganoderma lucidum (30.1%),
      Schizophyllum commune (27.6%), and Hericium erinaceus (17.7%) showed relatively
      high AI. Total phenolics in these mushrooms varied between 6.19 to 63.51 mg GAE/g
      extract. In the ACE inhibitory assay, G. lucidum was shown to be the most potent
      species (IC(50) = 50 MUg/mL). Based on our findings, culinary-medicinal mushrooms
      can be considered as potential source of dietary antioxidant and ACE inhibitory
      agents.

PMID- 21716694
TI  - Activation of the GLP-1 receptor signalling pathway: a relevant strategy to
      repair a deficient beta-cell mass.
AB  - Recent preclinical studies in rodent models of diabetes suggest that exogenous
      GLP-1R agonists and DPP-4 inhibitors have the ability to increase islet mass and
      preserve beta-cell function, by immediate reactivation of beta-cell glucose
      competence, as well as enhanced beta-cell proliferation and neogenesis and
      promotion of beta-cell survival. These effects have tremendous implication in the
      treatment of T2D because they directly address one of the basic defects in T2D,
      that is, beta-cell failure. In human diabetes, however, evidence that the GLP-1
      based drugs alter the course of beta-cell function remains to be found. Several
      questions surrounding the risks and benefits of GLP-1-based therapy for the
      diabetic beta-cell mass are discussed in this review and require further
      investigation.

PMID- 21716695
TI  - Ill Effects of Smoking: Baseline Knowledge among School Children and
      Implementation of the "AntE Tobacco" Project.
AB  - Introduction. Cigarette smoking contributes to the deaths of more than 400,000
      Americans annually. Each day >3,000 children and adolescents become regular
      smokers. This paper details a new antitobacco educational program titled "AntE
      Tobacco" Method. Children in grades 1-3 were administered a 10-item questionnaire
      to ascertain their baseline knowledge about the ill effects of smoking, shown an
      educational cartoon video depicting the ill effects of tobacco, and given a story
      book based on the video. At the end of video, children were administered a
      questionnaire to determine short-term recall of the antitobacco educational
      objectives of the program. Four to 6 weeks later, the children were then
      administered a follow-up survey to determine long-term retention of the anti
      tobacco educational program. Result. Eighty two percent of the children answered
      the outcome questions correctly immediately following the video. At follow-up, 4
      6 weeks later, 83% of children answered all questions correctly. Conclusion. The
      anti tobacco education program used in this study effectively conveyed most of
      the educational objectives. The results of this study indicate that a multimedia
      (i.e., video and book) educational program can be used to educate and reinforce
      anti tobacco messages. This program may be very useful as a part of a
      comprehensive anti tobacco curriculum in school systems.

PMID- 21716696
TI  - Use of specific chemical reagents for detection of modified nucleotides in RNA.
AB  - Naturally occurring cellular RNAs contain an impressive number of chemically
      distinct modified residues which appear posttranscriptionally, as a result of
      specific action of the corresponding RNA modification enzymes. Over 100 different
      chemical modifications have been identified and characterized up to now.
      Identification of the chemical nature and exact position of these modifications
      is typically based on 2D-TLC analysis of nucleotide digests, on HPLC coupled with
      mass spectrometry, or on the use of primer extension by reverse transcriptase.
      However, many modified nucleotides are silent in reverse transcription, since the
      presence of additional chemical groups frequently does not change base-pairing
      properties. In this paper, we give a summary of various chemical approaches
      exploiting the specific reactivity of modified nucleotides in RNA for their
      detection.

PMID- 21716697
TI  - The selfish grandma gene: the roles of the x-chromosome and paternity uncertainty
      in the evolution of grandmothering behavior and longevity.
AB  - When considering inclusive fitness, it is expected that individuals will provide
      more care towards those with whom they are more closely related. Thus, if a
      selfish X-linked genetic element influenced care giving, we would expect care
      giving to vary with X-relatedness. Recent studies have shown that X-chromosome
      inheritance patterns may influence selection of traits affecting behavior and
      life-history. Sexually antagonistic (SA) zygotic drive could encourage
      individuals to help those with whom they are more likely to share genetic
      material at the expense of other relatives. We reanalyze previously reported data
      in light of this new idea. We also evaluate the effects of paternity uncertainty
      on SA-zygotic drive. Our evidence suggests that human paternal discrepancy is
      relatively low. Using published models, we find the effects of paternal
      discrepancy do not override opportunity for selection based on X-relatedness.
      Based on these results, longevity and grandmothering behaviors, including
      favoritism, may be more heavily influenced by selection on the X-chromosome than
      by paternity uncertainty.

PMID- 21716698
TI  - Early detection of nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a unique disease with a clinical presentation,
      epidemiology, and histopathology differing from other squamous cell carcinomas of
      the head and neck. NPC is an Epstein-Barr virus-associated malignancy with a
      marked racial and geographic distribution. Specifically, it is highly prevalent
      in southern China, Southeast Asia, and the Middle East. To date, most NPC
      patients have been diagnosed in the advanced stage, but the treatment results for
      advanced NPC are not satisfactory. This paper provides a brief overview regarding
      NPC, with the focus on the early detection of initial and recurrent NPC lesions.

PMID- 21716699
TI  - Biopsy-Proven Acute Tubular Necrosis due to Vancomycin Toxicity.
AB  - Vancomycin (VAN) has been associated with acute kidney injury (AKI) since it has
      been put into clinical use in the 1950's. Early reports of AKI were likely linked
      to the impurities of the VAN preparation. With the advent of the more purified
      forms of VAN, the incidence of AKI related to VAN were limited to acute
      interstitial nephritis (AIN) or as a potentiating agent to other nephrotoxins
      such as Aminoglycosides. VAN as the sole etiologic factor for nephrotoxic acute
      tubular necrosis (ATN) has not been described. Here, we report a case of biopsy
      proven ATN resulting from VAN.

PMID- 21716700
TI  - A giant euthyroid endemic multinodular goiter with no obstructive or compressive
      symptoms.
AB  - Diffusely enlarged thyroid glands (goitres) are becoming increasingly infrequent.
      However, in some geographical areas they are still relatively common and can
      cause compressive symptoms involving the trachea, oesophagus, and recurrent
      laryngeal nerve. Surgical treatment of diffusely enlarged thyroid glands requires
      a high level of expertise and may lead to severe complications. Here we present a
      case report of surgical treatment of an extremely enlarged thyroid gland, found
      in a 61-year-old female patient. The patient underwent surgery, and a
      thyroidectomy was performed. The resulting specimen weighed 4.7 kg (10.4 lbs).
      Histopathological examination revealed a multinodular goitre with multiple cysts
      and areas of haemorrhage and necrosis. Surgical excision can immediately resolve
      local symptoms and is often recommended when substernal extension is evident. To
      the best of our knowledge, this is the largest thyroid gland ever reported in the
      literature. Only experienced surgeons should treat large thyroid goitres.
      Ideally, large thyroid goitres should be treated before they reach a substernal
      component, otherwise any sudden growth in gland size could seriously compromise
      respiration.

PMID- 21716701
TI  - Late life-threatening hemorrhage after percutaneous tracheostomy.
AB  - Purpose. Formation of a tracheoinnominate artery fistula (TIF) and consecutive
      hemorrhage is a rare and life-threatening complication with high mortality.
      Warning symptoms can be absent. The current literature contains only few
      considerations for misleading signs, especially in cases where the contact
      between the tissue and the cannula is tight. Method and Results. We report two
      cases of life-threatening hemorrhages that appeared six days and two months after
      percutaneous dilatational tracheostomy (PDT) in two patients, respectively. In
      these cases, diagnosis of tracheoinnominate artery fistula (TIF) was difficult.
      Tracheal ring fracture after PDT and pressure ulceration caused by cannula were
      implicated in TIF formation. The cannula was overblocked to buy time before
      surgical closure. Both patients survived without any additional neurological
      deficiency. Conclusion. Massive hemorrhage in patients after tracheostomy is
      likely due to TIF. Ultrasound scanning before PDT and careful periodical followup
      of the trachea are required.

PMID- 21716702
TI  - Depression and anxiety in patients with chronic renal failure: the effect of
      sociodemographic characteristics.
AB  - "Do the sociodemographic characteristics relate to the levels of depression and
      anxiety in patients with chronic renal failure in Athens?" The study investigated
      in a group of renal disease patients differences referring to self-reported
      mental health, depression, and anxiety, after controlling for gender, age,
      education, and marital status. Patient-reported assessments included General
      Health Questionnaire (GHQ-28) of Goldberg, Center for Epidemiological Studies
      Depression Scale (CES-D), and State-Trait Anxiety Inventory (STAI I & II) of
      Spielberger. Female patients reported higher scores in the trait anxiety measure.
      Elder patients reported higher scores in the GHQ-28 subscale of social
      dysfunction and in the CES-D depression scale, while less educated patients
      presented higher scores in the GHQ-28 subscales of anxiety/insomnia and severe
      depression. Divorced/widowed patients presented higher scores in the severe
      depression subscale. Findings provide evidence that sociodemographic variables,
      like being older, less educated, and divorced/widowed, relate to a more
      compromised mental health.

PMID- 21716703
TI  - A new microarray system to detect Streptococcus pneumoniae serotypes.
AB  - Streptococcus pneumoniae, one of the most common gram-positive pathogens to
      colonize the human upper respiratory tract, is responsible for many severe
      infections, including meningitis and bacteremia. A 23-valent pneumococcal vaccine
      is available to protect against the 23 S. pneumoniae serotypes responsible for
      90% of reported bacteremic infections. Unfortunately, current S. pneumoniae
      serotype testing requires a large panel of expensive antisera, assay results may
      be subjective, and serotype cross-reactions are common. For this study, we
      designed an oligonucleotide-based DNA microarray to identify glycosyltransferase
      gene sequences specific to each vaccine-related serotype. Out of 56 isolates
      representing different serotypes, only one isolate, representing serotype 23A,
      was not detected correctly as it could not be distinguished from serotype 23F.
      Our data suggest that the microarray provides a more cost-effective and reliable
      way of monitoring pneumococcal capsular types.

PMID- 21716704
TI  - Peritoneal dialysis in renal replacement therapy for patients with acute kidney
      injury.
AB  - Peritoneal dialysis (PD) was the first modality used for renal replacement
      therapy (RRT) of patients with acute kidney injury (AKI) because of its inherent
      advantages as compared to Hemodialysis. It provides the nephrologist with
      nonvascular alternative for renal replacement therapy. It is an inexpensive
      modality in developing countries and does not require highly trained staff or a
      complex apparatus. Systemic anticoagulation is not needed, and it can be easily
      initiated. It can be used as continuous or intermittent procedure and, due to
      slow fluid and solute removal, helps maintain hemodynamic stability especially in
      patients admitted to the intensive care unit. PD has been successfully used in
      AKI involving patients with hemodynamic instability, those at risk of bleeding,
      and infants and children with AKI or circulatory failure. Newer continuous renal
      replacement therapies (CRRTs) are being increasingly used in renal replacement
      therapy of AKI with less use of PD. Results of studies comparing newer modalities
      of CRRT versus acute peritoneal dialysis have been conflicting. PD is the
      modality of choice in renal replacement therapy in pediatric patients and in
      patients with AKI in developing countries.

PMID- 21716705
TI  - Blood Loss through AV Fistula: A Case Report and Literature Review.
AB  - Little has been written about acute blood loss from hemodialysis vascular access.
      We describe a 57-year-old Caucasian male with an approximately 7 gm/dL drop in
      hemoglobin due to bleeding from a ruptured aneurysm in his right brachiocephalic
      arteriovenous fistula (AVF). There was no evidence of fistula infection. The
      patient was successfully managed by blood transfusions and insertion of a
      tunneled dialysis catheter for dialysis access. Later, the fistula was ligated
      and a new fistula was constructed in the opposite arm. Aneurysm should be
      considered in cases of acute vascular access bleeding in chronic dialysis
      patients.

PMID- 21716706
TI  - Effects of the Use of Non-Calcium Phosphate Binders in the Control and Outcome of
      Vascular Calcifications: A Review of Clinical Trials on CKD Patients.
AB  - Vascular calcifications produce a high impact on morbidity and mortality rates in
      patients affected by chronic kidney disease and mineral bone disorder (CKD-MBD).
      Effects are manifested from the more advanced stages of CKD (stages 3-4),
      particularly in patients undergoing dialysis (CKD5D). In recent years, a large
      number of therapeutic options have been successfully used in the treatment of
      secondary hyperparathyroidism (SHPT), despite eliciting less marked effects on
      nonbone calcifications associated with CKD-MBD. In addition to the use of Vitamin
      D and analogues, more recently treatment with calcimimetic drugs has also been
      undertaken. The present paper aims to analyze comparative and efficacy studies
      undertaken to assess particularly the impact on morbidity and mortality rates of
      non-calcium phosphate binders. Moreover, the mechanism of action underlying the
      depositing of calcium and phosphate along blood vessel walls, irrespective of the
      specific contribution provided in reducing the typical phosphate levels observed
      in CKD largely at more advanced stages of the disease, will be investigated. The
      aim of this paper therefore is to evaluate which phosphate binders are
      characterised by the above action and the mechanisms through which these are
      manifested.

PMID- 21716707
TI  - Effects of the Topical Application of Hydroalcoholic Leaf Extract of Oncidium
      flexuosum Sims. (Orchidaceae) and Microcurrent on the Healing of Wounds
      Surgically Induced in Wistar Rats.
AB  - This study evaluated the wound healing activity of hydroalcoholic leaf extract of
      Oncidium flexuosum Sims. (Orchidaceae), an important native plant of Brazil,
      combined or not with microcurrent stimulation. Wistar rats were randomly divided
      into four groups of nine animals: control (C), topical application of the extract
      (OF), treated with a microcurrent (10 MUA/2 min) (MC), and topical application of
      the extract plus microcurrent (OF + MC). Tissue samples were obtained 2, 6, and
      10 days after injury and submitted to structural and morphometric analysis. The
      simultaneous application of OF + MC was found to be highly effective in terms of
      the parameters analyzed (P < .05), with positive effects on the area of newly
      formed tissue, number of fibroblasts, number of newly formed blood vessels, and
      epithelial thickness. Morphometric data confirmed the structural findings. The O.
      flexuosum leaf extract contains active compounds that speed the healing process,
      especially when applied simultaneously with microcurrent stimulation.

PMID- 21716708
TI  - A randomized, controlled trial of meditation for work stress, anxiety and
      depressed mood in full-time workers.
AB  - Objective. To assess the effect of meditation on work stress, anxiety and mood in
      full-time workers. Methods. 178 adult workers participated in an 8-week, 3-arm
      randomized controlled trial comparing a "mental silence" approach to meditation
      (n = 59) to a "relaxation" active control (n = 56) and a wait-list control (n =
      63). Participants were assessed before and after using Psychological Strain
      Questionnaire (PSQ), a subscale of the larger Occupational Stress Inventory
      (OSI), the State component of the State/Trait Anxiety Inventory for Adults
      (STAI), and the depression-dejection (DD) subscale of the Profile of Mood States
      (POMS). Results. There was a significant improvement for the meditation group
      compared to both the relaxation control and the wait-list groups the PSQ (P =
      .026), and DD (P = .019). Conclusions. Mental silence-orientated meditation, in
      this case Sahaja Yoga meditation, is a safe and effective strategy for dealing
      with work stress and depressive feelings. The findings suggest that "thought
      reduction" or "mental silence" may have specific effects relevant to work stress
      and hence occupational health.

PMID- 21716709
TI  - A randomized controlled trial of auricular transcutaneous electrical nerve
      stimulation for managing posthysterectomy pain.
AB  - Background. A patient- and assessor-blinded randomized controlled trial was
      conducted to examine the effectiveness of auricular transcutaneous electrical
      nerve stimulation (TENS) in relieving posthysterectomy pain. Method. Forty-eight
      women who had undergone a total abdominal hysterectomy were randomly assigned
      into three groups (n = 16 each) to receive either (i) auricular TENS to
      therapeutic points (the true TENS group), (ii) auricular TENS to inappropriate
      points (the sham TENS group), or (iii) 20 minutes of bed rest with no stimulation
      (the control group). The intervention was delivered about 24 hours after the
      operation. A visual analogue scale was used to assess pain while resting (VAS
      rest) and upon huffing (VAS-huff) and coughing (VAS-cough), and the peak
      expiratory flow rate (PEFR) was assessed before and at 0, 15, and 30 minutes
      after the intervention. Result. As compared to the baseline, only the true TENS
      group reported a significant reduction in VAS-rest (P = .001), VAS-huff (P =
      .004), and VAS-cough (P = .001), while no significant reduction in any of the VAS
      scores was seen in the sham TENS group (all P > .05). In contrast, a small rising
      trend was observed in the VAS-rest and VAS-huff scores of the control group,
      while the VAS-cough score remained largely unchanged during the period of the
      study. A between-group comparison revealed that all three VAS scores of the true
      TENS group were significantly lower than those of the control group at 15 and 30
      minutes after the intervention (all P < .02). No significant between-group
      difference was observed in PEFR at any point in time. Conclusion. A single
      session of auricular TENS applied at specific therapeutic points significantly
      reduced resting (VAS-rest) and movement-evoked pain (VAS-huff, VAS-cough), and
      the effects lasted for at least 30 minutes after the stimulation. The analgesic
      effects of auricular TENS appeared to be point specific and could not be
      attributed to the placebo effect alone. However, auricular TENS did not produce
      any significant improvement in the performance of PEFR.

PMID- 21716710
TI  - Efficacy of Brazilian Propolis against Herpes Simplex Virus Type 1 Infection in
      Mice and Their Modes of Antiherpetic Efficacies.
AB  - Ethanol extracts (AF-06, 07, and 08, 10 mg/kg) of Brazilian propolis were
      administered orally to cutaneously herpes simplex virus type 1 (HSV-1)-infected
      mice three times daily on days 0 to 6 after infection to evaluate their
      efficacies against HSV-1 infection and significantly limited development of
      herpetic skin lesions. AF-07 and 08 significantly reduced virus titers in brain
      and/or skin on day 4 without toxicity, but AF-08 had no anti-HSV-1 activity in
      vitro. AF-06 and 08 significantly enhanced delayed-type hypersensitivity (DTH) to
      inactivated HSV-1 antigen in infected mice. Oral AF-08-administration
      significantly augmented interferon (IFN)-gamma production by HSV-1 antigen from
      splenocytes of HSV-1-infected mice, while direct exposure of splenocytes of
      infected mice to AF-06 significantly elevated IFN-gamma production in vitro.
      Thus, AF-08 might have components that are active in vivo even after oral
      administration and those of AF-06 might be active only in vitro. Because DTH is a
      major host defense for intradermal HSV-1 infection, augmentation of DTH response
      by AF-06 or 08, directly or indirectly, respectively, may contribute to their
      efficacies against HSV-1 infection. In addition, AF-06 and 07 possibly contain
      anti-HSV-1 components contributing to their efficacies. Such biological
      activities of Brazilian propolis may be useful to analyze its pharmacological
      actions.

PMID- 21716711
TI  - Practices in wound healing studies of plants.
AB  - Wounds are the result of injuries to the skin that disrupt the other soft tissue.
      Healing of a wound is a complex and protracted process of tissue repair and
      remodeling in response to injury. Various plant products have been used in
      treatment of wounds over the years. Wound healing herbal extracts promote blood
      clotting, fight infection, and accelerate the healing of wounds.
      Phytoconstituents derived from plants need to be identified and screened for
      antimicrobial activity for management of wounds. The in vitro assays are useful,
      quick, and relatively inexpensive. Small animals provide a multitude of model
      choices for various human wound conditions. The study must be conducted after
      obtaining approval of the Ethics Committee and according to the guidelines for
      care and use of animals. The prepared formulations of herbal extract can be
      evaluated by various physicopharmaceutical parameters. The wound healing
      efficacies of various herbal extracts have been evaluated in excision, incision,
      dead space, and burn wound models. In vitro and in vivo assays are stepping
      stones to well-controlled clinical trials of herbal extracts.

PMID- 21716712
TI  - Needle-free electroacupuncture for postoperative pain management.
AB  - This study examined the effects of needle-free electroacupuncture, at ST36 on
      postoperative pain following hysterectomy. Based on a double-blind, sham and
      different intervention controlled clinical experimental design, 47 women were
      randomly allocated to four different groups. Except for those in the control
      group (Group 1, n = 13), a course of treatment was given of either sham (Group 2,
      n = 12), high-frequency stimulation (Group 3, n = 12), or low-frequency
      stimulation (Group 4, n = 10). All groups were assessed during the postoperative
      period for 24 hours. The Visual Analogue Scale was used to determine the amount
      of perceived pain felt by each subject. Differences were found between the means
      postoperatively at three, four, eight, 16 and 24 hours. Post hoc comparison tests
      indicated that Group 4 was significantly different from Groups 1, 2, and 3 at 24
      hours. A one-way ANOVA analysis for total patient-controlled analgesia demand and
      doses indicated significant differences between the groups F(3, 42) = 3.59, P <
      .05. Post hoc analysis confirmed the differences between Groups 1 (M = 84.54) and
      4 (M = 41.60). Treatment outcomes of this therapy showed a positive effect for
      the management of postoperative pain.

PMID- 21716713
TI  - Acute renal replacement therapy in pediatrics.
AB  - Acute kidney injury (AKI) independently increases morbidity and mortality in
      children admitted to the hospital. Renal replacement therapy (RRT) is an
      essential therapy in the setting of AKI and fluid overload. The decision to
      initiate RRT is complex and often complicated by concerns related to patient
      hemodynamic and thermodynamic instability. The choice of which RRT modality to
      use depends on numerous criteria that are both patient and treatment center
      specific. Surprisingly, despite decades of use, no randomized, controlled trial
      study involving RRT in pediatrics has been performed. Because of these factors,
      clear-cut consensus is lacking regarding key questions surrounding RRT delivery.
      In this paper, we will summarize existing data concerning RRT use in children. We
      discuss the major modalities and the data-driven specifics of each, followed by
      controversies in RRT. As no standard of care is in widespread use for RRT in AKI
      or in multiorgan disease, we conclude in this paper that prospective studies of
      RRT are needed to identify best practice guidelines.

PMID- 21716714
TI  - In Vitro and In Vivo Activities of Essential Oil from the Seed of Anethum
      graveolens L. against Candida spp.
AB  - The essential oil produced from the seed of Anethum graveolens L. (Umbelliferae)
      was tested in vitro and in vivo anti-Candida activity. The microbroth dilution
      method was used in the minimal inhibitory concentration (MIC), according to M27
      A3 of the guidelines of the Clinical and Laboratory Standard Institute (CLSI).
      And then, efficacy evaluation of essential oil in the prophylaxis and treatment
      of experimental vaginal candidiasis was performed in immunosuppressed mice. The
      anti-Candida activity was analyzed by microbiological and histological techniques
      and was compared with that of fluconazole (FCZ). The results showed essential oil
      was active in vitro against all tested strains, with MICs ranging from 0.312
      MUL/mL (for C. tropicalis, C. parapsilosis, and C. krusei) to 0.625 MUL/mL (for 6
      isolated C. albicans strains). Essential oil (2% v/v) was highly efficacious in
      accelerating C. albicans 09-1555 clearance from experimentally infected mice
      vagina by prophylaxis and therapeutic treatments. In both therapeutic efficacy
      and prophylaxis studies, the histological findings confirmed the microbiological
      results. The experimental results revealed that the tested essential oil is
      effective against vulvovaginal candidiasis in immunosuppressed mice.

PMID- 21716715
TI  - Sipuleucel-T: autologous cellular immunotherapy for men with asymptomatic or
      minimally symptomatic metastatic castrate resistant prostate cancer.
AB  - Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an
      immune response in men diagnosed with asymptomatic or minimally symptomatic
      metastatic castrate resistant (hormone refractory) prostate cancer. Sipuleucel T
      improves overall survival and provides an additional treatment option for this
      patient population.

PMID- 21716716
TI  - Adoptive cell therapy for patients with melanoma.
AB  - Adoptive cell therapy can be an effective treatment for some patients with
      advanced cancer. This report summarizes clinical trial results from the Surgery
      Branch, NCI, investigating tumor infiltrating lymphocytes (TIL) and gene
      engineered peripheral blood T cells for the therapy of patients with melanoma and
      other solid tumors.

PMID- 21716717
TI  - Cytokine induced killer cells as promising immunotherapy for solid tumors.
AB  - Cytokine-induced killer (CIK) cells are a heterogeneous subset of ex-vivo
      expanded T lymphocytes which present a mixed T-NK phenotype and are endowed with
      a MHC-unrestricted antitumor activity. The main functional properties of CIK
      cells may address some of the main limitations that are currently preventing the
      successful clinical translation of adoptive immunotherapy strategies. Clinically
      adequate quantities of immune effectors, sufficient for multiple adoptive
      infusions, may be obtained based on their relatively easy and inexpensive ex-vivo
      expansion starting from peripheral blood mononuclear cells. The MHC-unrestricted
      tumor-killing is mainly based on the interaction between NKG2D molecules on CIK
      cells and MIC A/B or ULBPs molecules on tumor cells; it has been proved effective
      against several solid and hematological malignancies and does not require any HLA
      restriction increasing the number of patients that might potentially benefit from
      such approach. Finally, CIK cells present a reduced alloreactivity across HLA
      barriers with important clinical implications for their potential use as
      alternative to conventional Donor Lymphocyte Infusions after allogeneic
      hemopoietic cell transplant with a reduced risk of GVHD. In the present report we
      review the main functional characteristics of CIK cells discussing recent
      findings and future perspectives to improve their antitumor activity and
      potential clinical applications.

PMID- 21716718
TI  - Associations between Variation in X Chromosome Male Reproductive Genes and Sperm
      Competitive Ability in Drosophila melanogaster.
AB  - Variation in reproductive success has long been thought to be mediated in part by
      genes encoding seminal proteins. Here we explore the effect on male reproductive
      phenotypes of X-linked polymorphisms, a chromosome that is depauperate in genes
      encoding seminal proteins. Using 57 X chromosome substitution lines, sperm
      competition was tested both when the males from the wild-extracted line were the
      first to mate ("defense" crosses), followed by a tester male, and when extracted
      line males were the second to mate, after a tester male ("offfense" crosses). We
      scored the proportion of progeny sired by each male, the fecundity, the remating
      rate and refractoriness to remating, and tested the significance of variation
      among lines. Eleven candidate genes were chosen based on previous studies, and
      portions of these genes were sequenced in all 57 lines. A total of 131
      polymorphisms were tested for associations with the reproductive phenotypes using
      linear models. Nine polymorphisms in 4 genes were found to show significant
      associations (at a 5% FDR). Overall, it appears that the X chromosomes harbor
      abundant variation in sperm competition, especially considering the paucity of
      seminal protein genes. This suggests that much of the male reproductive variation
      lies outside of genes that encode seminal proteins.

PMID- 21716719
TI  - Tenofovir nephrotoxicity: 2011 update.
AB  - Tenofovir is an acyclic nucleotide analogue reverse-transcriptase inhibitor
      structurally similar to the nephrotoxic drugs adefovir and cidofovir. Tenofovir
      is widely used to treat HIV infection and approved for treatment of hepatitis B
      virus. Despite initial cell culture and clinical trials results supporting the
      renal safety of tenofovir, its clinical use is associated with a low, albeit
      significant, risk of kidney injury. Proximal tubular cell secretion of tenofovir
      explains the accumulation of the drug in these mitochondria-rich cells. Tenofovir
      nephrotoxicity is characterized by proximal tubular cell dysfunction that may be
      associated with acute kidney injury or chronic kidney disease. Withdrawal of the
      drug leads to improvement of analytical parameters that may be partial.
      Understanding the risk factors for nephrotoxicity and regular monitoring of
      proximal tubular dysfunction and serum creatinine in high-risk patients is
      required to minimize nephrotoxicity. Newer, structurally similar molecular
      derivatives that do not accumulate in proximal tubules are under study.

PMID- 21716720
TI  - The Rieske Iron-Sulfur Protein: Import and Assembly into the Cytochrome bc(1)
      Complex of Yeast Mitochondria.
AB  - The Rieske iron-sulfur protein, one of the catalytic subunits of the cytochrome
      bc(1) complex, is involved in electron transfer at the level of the inner
      membrane of yeast mitochondria. The Rieske iron-sulfur protein is encoded by
      nuclear DNA and, after being synthesized in the cytosol, is imported into
      mitochondria with the help of a cleavable N-terminal presequence. The imported
      protein, besides incorporating the 2Fe-2S cluster, also interacts with other
      catalytic and non-catalytic subunits of the cytochrome bc(1) complex, thereby
      assembling into the mature and functional respiratory complex. In this paper, we
      summarize the most recent findings on the import and assembly of the Rieske iron
      sulfur protein into Saccharomyces cerevisiae mitochondria, also discussing a
      possible role of this protein both in the dimerization of the cytochrome bc(1)
      complex and in the interaction of this homodimer with other complexes of the
      mitochondrial respiratory chain.

PMID- 21716721
TI  - The psoas compartment block for hip surgery: the past, present, and future.
AB  - A posterior lumbar plexus block or psoas compartment block (PCB) is an effective
      locoregional anesthetic technique for analgesia and anesthesia of the entire
      lower extremity including the hip. Since the first description in the early
      seventies, this technique has been modified based on advanced knowledge of the
      anatomical localization of the lumbar plexus and the improvement of technical
      equipment. This paper provides an overview of the history, clinical efficacy, and
      risk profile of the PCB focused on hip surgery. Current status and future
      expectations are discussed.

PMID- 21716722
TI  - Serum positive for the autoantibody against the beta(1)-adrenoceptor from Chinese
      patients with congestive heart failure decreases I(ss) in mouse cardiac myocytes.
AB  - Autoantibodies targeting the beta(1)-adrenergic receptor (AAB-beta(1)) display
      agonist-like effects, which may have a pathogenic role in the progression of
      heart failure. Here, we used the electrophysiological recordings to explore the
      effects of AAB-beta(1)-positive serum from Chinese patients with heart failure on
      the activity of the peak transient outward potassium current (I(to)) and the end
      50 ms steady-state potassium current (I(ss)) in mouse cardiac myocytes. We found
      that the AAB-beta(1)-positive serum had no effect on the activity of I(to), but
      it produced a decrease in the currents of I(ss). A low concentration of positive
      serum (1/100) had a small inhibitory effect on I(ss). However, positive serum at
      1 : 10, 1 : 20, and 1 : 50 significantly decreased I(ss). The concentration
      dependence analysis showed that the EC(50) of AAB-beta(1)-positive serum was
      1/60.24 and its nH was 2.86. It indicated that the AAB-beta(1) could inhibit
      I(ss) in mouse cardiomyocyte in a concentration-dependent manner.

PMID- 21716723
TI  - The utility of geometric morphometrics to elucidate pathways of cichlid fish
      evolution.
AB  - Fishes of the family Cichlidae are famous for their spectacular species flocks
      and therefore constitute a model system for the study of the pathways of adaptive
      radiation. Their radiation is connected to trophic specialization, manifested in
      dentition, head morphology, and body shape. Geometric morphometric methods have
      been established as efficient tools to quantify such differences in overall body
      shape or in particular morphological structures and meanwhile found wide
      application in evolutionary biology. As a common feature, these approaches define
      and analyze coordinates of anatomical landmarks, rather than traditional counts
      or measurements. Geometric morphometric methods have several merits compared to
      traditional morphometrics, particularly for the distinction and analysis of
      closely related entities. Cichlid evolutionary research benefits from the
      efficiency of data acquisition, the manifold opportunities of analyses, and the
      potential to visualize shape changes of those landmark-based methods. This paper
      briefly introduces to the concepts and methods of geometric morphometrics and
      presents a selection of publications where those techniques have been
      successfully applied to various aspects of cichlid fish diversification.

PMID- 21716724
TI  - Virological breakthrough: a risk factor for loss to followup in a large community
      based cohort on antiretroviral therapy.
AB  - Background. We have previously shown that 75% of individuals on antiretroviral
      therapy (ART) in a resource-limited setting who experienced virological
      breakthrough to >1000 copies/mL were resuppressed after an intensive adherence
      intervention. This study examines the long-term outcomes of this group in order
      to understand the impact of the adherence intervention over time. Methods. ART
      naive adults commencing ART between September 2002 and December 2009 were
      reviewed. Those who achieved suppression (<50 copies/mL) were categorised by
      subsequent viral load: any >1000 copies/mL (virological breakthrough) or not.
      Those with breakthrough were sub-categorised by following viral load into failed
      (VL > 1000 copies/mL) or resuppressed (VL < 1000 copies/mL). Their outcome (lost
      to follow-up, death, in care on first-line therapy or in care on second-line
      therapy) was determined as of the 13th April 2010. Findings. 4047 ART-naive
      adults commenced ART. 3086 had >2 viral loads and were included in the analysis.
      2959 achieved virological suppression (96%). Thereafter 2109 (71%) remained
      suppressed and 850 (29%) experienced breakthrough (n = 283 (33%) failed and n =
      567 (67%) resuppressed). Individuals with breakthrough were younger (P < .001),
      had lower CD4 counts (P < .001), and higher viral loads (P < .001) than those who
      remained suppressed. By 7 years the risk of breakthrough was 42% and of failure
      15%. Fewer adults with breakthrough remain in care over time (P < .001). Loss to
      care is similar whether the individuals failed or resuppressed. Interpretation.
      While 67% of those who experience initial virological breakthrough resuppress
      after an adherence intervention, these individuals are significantly less likely
      be retained in care than those who remain virologically suppressed throughout.

PMID- 21716725
TI  - Axillary brachial plexus block.
AB  - The axillary approach to brachial plexus blockade provides satisfactory
      anaesthesia for elbow, forearm, and hand surgery and also provides reliable
      cutaneous anaesthesia of the inner upper arm including the medial cutaneous nerve
      of arm and intercostobrachial nerve, areas often missed with other approaches. In
      addition, the axillary approach remains the safest of the four main options, as
      it does not risk blockade of the phrenic nerve, nor does it have the potential to
      cause pneumothorax, making it an ideal option for day case surgery. Historically,
      single-injection techniques have not provided reliable blockade in the
      musculocutaneous and radial nerve territories, but success rates have greatly
      improved with multiple-injection techniques whether using nerve stimulation or
      ultrasound guidance. Complete, reliable, rapid, and safe blockade of the arm is
      now achievable, and the paper summarizes the current position with particular
      reference to ultrasound guidance.

PMID- 21716727
TI  - Evolutionary mechanisms of microbial genomes.

PMID- 21716726
TI  - Lymph node transplantation and its immunological significance in animal models.
AB  - Lymph nodes (LNs) are distributed all over the body and whatever the site
      consists of the same cell populations. However, there are great differences
      between LN from different draining areas. For example, in mesenteric LN, homing
      molecules, for example, CCR9 and alpha4beta7 integrin, were induced and
      cytokines, for example, IL-4, were produced on higher levels compared to
      peripheral LN. To study the immunological functions of LN, LN transplantation was
      performed in some specific areas using different animal models. Many groups
      investigated not only the regeneration of transplanted LN but also the induction
      of immune responses or tolerance after transplantation. Existing differences
      between LNs were still detectable after transplantation. Most important, stromal
      cells of the LN were identified as responsible for these differences. They
      survive during regeneration and were shown to reconstruct not only the structure
      of the new LN but also the microenvironment.

PMID- 21716728
TI  - Humoral immune response to keyhole limpet haemocyanin, the protein carrier in
      cancer vaccines.
AB  - Keyhole limpet haemocyanin (KLH) appears to be a promising protein carrier for
      tumor antigens in numerous cancer vaccine candidates. The humoral immune response
      to KLH was characterized at the single-cell level with ELISPOT combined with
      separations of cell populations according to their expression of homing receptors
      (HRs). The analysis of HR expressions is expected to reveal the targeting of the
      immune response in the body. Eight orally primed and four nonprimed volunteers
      received KLH-vaccine subcutaneously. Circulating KLH-specific plasmablasts were
      found in all volunteers, 60 KLH-specific plasmablasts/10(6) PBMC in the nonprimed
      and 136/10(6) in the primed group. The proportion of L-selectin(+) plasmablasts
      proved high and integrin alpha(4)beta(7) (+) low. KLH serving as protein carrier
      in several vaccines, the homing profile of KLH-specific response may be
      applicable to the cancer antigen parts in the same vaccines. The present data
      reflect a systemic homing profile, which appears advantageous for the targeting
      of immune response to cancer vaccines.

PMID- 21716729
TI  - Repeatability and heritability of behavioural types in a social cichlid.
AB  - Aim. The quantitative genetics underlying correlated behavioural traits (''animal
      personality") have hitherto been studied mainly in domesticated animals. Here we
      report the repeatability (R) and heritability (h(2)) of behavioural types in the
      highly social cichlid fish Neolamprologus pulcher. Methods. We tested 1779
      individuals repeatedly and calculated the h(2) of behavioural types by variance
      components estimation (GLMM REML), using 1327 offspring from 162 broods from 74
      pairs. Results. Repeatability of behavioural types was significant and
      considerable (0.546), but declined from 0.83 between tests conducted on the same
      day, to 0.19 on tests conducted up to 1201 days apart. All h(2) estimates were
      significant but low (e.g., pair identity h(2) = 0.15 +/- 0.03 SE). Additionally,
      we found significant variation between broods nested within the parent(s), but
      these were not related to several environmental factors tested. Conclusions. We
      conclude that despite a considerable R, h(2) in this cichlid species is low, and
      variability in behavioural type appears to be strongly affected by other
      (non)genetic effects.

PMID- 21716730
TI  - Neural blockade anaesthesia of the mandibular nerve and its terminal branches:
      rationale for different anaesthetic techniques including their advantages and
      disadvantages.
AB  - Anaesthesia of structures innervated by the mandibular nerve is necessary to
      provide adequate pain control when performing dental and localised surgical
      procedures. To date, numerous techniques have been described and, although many
      of these methods are not used routinely, there are some situations where their
      application may be indicated. Patient factors as well as anatomical variability
      of the mandibular nerve and associated structures dictate that no one technique
      can be universally applied with a 100% success rate. This fact has led to a
      proliferation of alternative techniques that have appeared in the literature.
      This selective review of the literature provides a brief description of the
      different techniques available to the clinician as well as the underlying anatomy
      which is fundamental to successfully anaesthetising the mandibular nerve.

PMID- 21716731
TI  - NOD dendritic cells stimulated with Lactobacilli preferentially produce IL-10
      versus IL-12 and decrease diabetes incidence.
AB  - Dendritic cells (DCs) from NOD mice produced high levels of IL-12 that induce
      IFNgamma-producing T cells involved in diabetes development. We propose to
      utilize the microorganism ability to induce tolerogenic DCs to abrogate the
      proinflammatory process and prevent diabetes development. NOD DCs were stimulated
      with Lactobacilli (nonpathogenic bacteria targeting TLR2) or lipoteichoic acid
      (LTA) from Staphylococcus aureus (TLR2 agonist). LTA-treated DCs produced much
      more IL-12 than IL-10 and accelerated diabetes development when transferred into
      NOD mice. In contrast, stimulation of NOD DCs with L. casei favored the
      production of IL-10 over IL-12, and their transfer decreased disease incidence
      which anti-IL-10R antibodies restored. These data indicated that L. casei can
      induce NOD DCs to develop a more tolerogenic phenotype via production of the anti
      inflammatory cytokine, IL-10. Evaluation of the relative production of IL-10 and
      IL-12 by DCs may be a very useful means of identifying agents that have
      therapeutic potential.

PMID- 21716732
TI  - Complex Regional Pain Syndrome Revived by Epileptic Seizure Then Disappeared Soon
      during Treatment with Regional Intravenous Nerve Blockade: A Case Report.
AB  - We present a case of complex regional pain syndrome (CRPS), in which symptoms,
      including burning pain and severe allodynia, were alleviated by using a regional
      intravenous nerve blockade (Bier block) combined with physiotherapy, but
      reappeared following an epileptic seizure. Symptoms disappeared again following
      control of epileptic discharges, as revealed by single-photon emission computed
      tomography (SPECT) and electroencephalography (EEG) results. Although systemic
      toxicity of a local anesthetic applied by Bier block was suspected as a cause of
      the first seizure, the patient did not present any other toxic symptoms, and
      seizures repeatedly occurred after Bier block cessation; the patient was then
      diagnosed as having temporal symptomatic epilepsy. This case suggests that
      symptoms of CRPS may be sustained by abnormal brain conditions, and our findings
      contribute to the understanding of how the central nervous system participates in
      maintaining pain and allodynia associated with CRPS.

PMID- 21716733
TI  - Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain
      Management following Hernia Repair Surgery.
AB  - Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for
      postoperative pain in patients undergoing hernia surgery. Methodology. Total 202
      patients received single intramuscular injection of dexketoprofen 50 mg or
      diclofenac 50 mg postoperatively. The pain intensity (PI) was self-evaluated by
      patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were
      number of responders, difference in PI (PID) at 8 hours, sum of analogue of pain
      intensity differences (SAPID), and onset and duration of analgesia. Tolerability
      assessment was done by global evaluation and adverse events in each group.
      Results. Dexketoprofen showed superior efficacy in terms of number of responders
      (P = .007), PID at 8 hours (P = .02), and SAPID( 0-8 hours ) (P < .0001). It also
      showed faster onset of action (42 minutes) and longer duration of action (6.5
      hours). The adverse events were comparable in both groups. Conclusion. Single
      dose of dexketoprofen trometamol 50 mg given intramuscularly provided faster,
      better, and longer duration of analgesia in postoperative patients of hernia
      repair surgery than diclofenac 50 mg, with comparable safety.

PMID- 21716734
TI  - Ultrasound-guided regional anesthesia for procedures of the upper extremity.
AB  - Anesthesia options for upper extremity surgery include general and regional
      anesthesia. Brachial plexus blockade has several advantages including decreased
      hemodynamic instability, avoidance of airway instrumentation, and intra-, as well
      as post-operative analgesia. Prior to the availability of ultrasound the risks of
      complications and failure of regional anesthesia made general anesthesia a more
      desirable option for anesthesiologists inexperienced in the practice of regional
      anesthesia. Ultrasonography has revolutionized the practice of regional
      anesthesia. By visualizing needle entry throughout the procedure, the
      relationship between the anatomical structures and the needle can reduce the
      incidence of complications. In addition, direct visualization of the spread of
      local anesthesia around the nerves provides instant feedback regarding the likely
      success of the block. This review article outlines how ultrasound has improved
      the safety and success of brachial plexus blocks. The advantages that ultrasound
      guidance provides are only as good as the experience of the anesthesiologist
      performing the block. For example, in experienced hands, with real time needle
      visualization, a supraclavicular brachial plexus block has changed from an
      approach with the highest risk of pneumothorax to a block with minimal risks
      making it the ideal choice for most upper extremity surgeries.

PMID- 21716735
TI  - A macroevolutionary perspective on multiple sexual traits in the phasianidae
      (galliformes).
AB  - Traits involved in sexual signaling are ubiquitous among animals. Although a
      single trait appears sufficient to convey information, many sexually dimorphic
      species exhibit multiple sexual signals, which may be costly to signalers and
      receivers. Given that one signal may be enough, there are many microevolutionary
      hypotheses to explain the evolution of multiple signals. Here we extend these
      hypotheses to a macroevolutionary scale and compare those predictions to the
      patterns of gains and losses of sexual dimorphism in pheasants and partridges.
      Among nine dimorphic characters, including six intersexual signals and three
      indicators of competitive ability, all exhibited both gains and losses of
      dimorphism within the group. Although theories of intersexual selection emphasize
      gain and elaboration, those six characters exhibited greater rates of loss than
      gain; in contrast, the competitive traits showed a slight bias towards gains. The
      available models, when examined in a macroevolutionary framework, did not yield
      unique predictions, making it difficult to distinguish among them. Even with this
      limitation, when the predictions of these alternative models were compared with
      the heterogeneous patterns of evolution of dimorphism in phasianids, it is clear
      that many different selective processes have been involved in the evolution of
      sexual signals in this group.

PMID- 21716736
TI  - Histological Consequences of Needle-Nerve Contact following Nerve Stimulation in
      a Pig Model.
AB  - Background. Nerve stimulation can facilitate correct needle placement in
      peripheral regional anesthesia. The aim of this study was to determine whether
      the high threshold current is associated with reduced nerve injury due to fewer
      needle-nerve contacts compared with low current. Methods. In anaesthetized pigs,
      thirty-two nerves of the brachial plexus underwent needle placement at low (0.2
      mA) or high current (1.0 mA). The occurrence of needle-nerve contact was
      recorded. After 48 hours, the nerves were analyzed for occurrence of histological
      changes. Nerve injury was scored ranging from 0 (no injury) to 4 (severe injury).
      Results. The frequency of needle-nerve contact was 94% at low compared to 6% at
      high current. The score was significantly higher at low (median [interquartile
      range] 2.0 [1.0-2.0]) compared to high current (0.0 [0.0-1.0] P = .001).
      Conclusions. Inflammatory responses were directly related to needle-nerve
      contacts. Hence, posttraumatic inflammation may be diminished using higher
      current for nerve localization.

PMID- 21716737
TI  - Persistent Copulation in Asexual Female Potamopyrgus antipodarum: Evidence for
      Male Control with Size-Based Preferences.
AB  - Transitions from sexual to asexual reproduction provide a useful context for
      investigating the evolutionary loss of nonfunctional traits. It is often assumed
      that useless behaviors or structures will degrade, but this process is poorly
      understood. Potamopyrgus antipodarum is an ancestrally sexual New Zealand
      freshwater snail characterized by numerous independent transitions to asexual all
      female lineages. The availability of multiple independently-derived asexual
      lineages of various time since derivation from sexual ancestors means that the P.
      antipodarum system is well-suited for the study of trait loss related to mating
      behavior and copulation. Here, we asked whether mating behavior in asexual female
      P. antipodarum degrades with increasing asexual lineage age. While copulation
      frequency did not differ in females from old versus young asexual lineages, post
      hoc analyses indicated that it was instead positively associated with mean
      lineage female size. We observed that female P. antipodarum take a passive
      physical role in copulatory interactions, indicating that female behavior may not
      be a useful variable for detection of sex-related vestigialization in this
      system. Instead, males seem to be in proximate control of copulation frequencies,
      meaning that male mating behavior may be a primary determinant of the expression
      of mating behavior in asexual female P. antipodarum.

PMID- 21716738
TI  - Male-Female Interactions and the Evolution of Postmating Prezygotic Reproductive
      Isolation among Species of the Virilis Subgroup.
AB  - Reproductive isolation reduces breeding between species. Traditionally,
      prezygotic and postzygotic barriers to reproduction have been broadly studied,
      but in recent years, attention has been brought to the existence of barriers that
      act after copulation but before fertilization. Here, we show that when D. virilis
      females from different geographic locations mate with D. novamexicana males, egg
      laying is normal, but fertilization rates are severely reduced, despite normal
      rates of sperm transfer. This reduction in fertilization is probably due to lower
      retention of heterospecific sperm in female storage organs one-to-two days after
      copulation. An inspection of egg hatchability in crosses between females and
      males from other virilis subgroup species reveals that isolation due to poor egg
      hatchability likely evolved during the diversification of D. virilis/D. lummei
      from species of the novamexicana-americana clade. Interestingly, the number of
      eggs laid by D. virilis females in heterospecific crosses was not different from
      the numbers of eggs laid in conspecific crosses, suggesting that females exert
      some form of cryptic control over the heterospecific ejaculate and that future
      studies should focus on how female and female-sperm interactions contribute to
      the loss or active exclusion of heterospecific sperm from storage.

PMID- 21716739
TI  - Segregation of species-specific male attractiveness in f(2) hybrid lake Malawi
      cichlid fish.
AB  - Among the huge radiations of haplochromine cichlid fish in Lakes Malawi and
      Victoria, closely related species are often reproductively isolated via female
      mate choice although viable fertile hybrids can be produced when females are
      confined only with heterospecific males. We generated F(2) hybrid males from a
      cross between a pair of closely related sympatric cichlid fish from Lake Malawi.
      Laboratory mate choice experiments using microsatellite paternity analysis
      demonstrated that F(2) hybrid males differed significantly in their
      attractiveness to females of the two parental species, indicating heritable
      variation in traits involved in mate choice that may contribute to reproductive
      isolation between these species. We found no significant correlation between male
      mating success and any measurement of male colour pattern. A simple quantitative
      genetic model of reproductive isolation suggests that there may be as few as two
      chromosomal regions controlling species-specific attractiveness. We propose that
      adaptive radiation of Lake Malawi cichlids could be facilitated by the presence
      of genes with major effects on mate choice and reproductive isolation.

PMID- 21716740
TI  - Baculovirus: molecular insights on their diversity and conservation.
AB  - The Baculoviridae is a large group of insect viruses containing circular double
      stranded DNA genomes of 80 to 180 kbp. In this study, genome sequences from 57
      baculoviruses were analyzed to reevaluate the number and identity of core genes
      and to understand the distribution of the remaining coding sequences. Thirty one
      core genes with orthologs in all genomes were identified along with other 895
      genes differing in their degrees of representation among reported genomes. Many
      of these latter genes are common to well-defined lineages, whereas others are
      unique to one or a few of the viruses. Phylogenetic analyses based on core gene
      sequences and the gene composition of the genomes supported the current division
      of the Baculoviridae into 4 genera: Alphabaculovirus, Betabaculovirus,
      Gammabaculovirus, and Deltabaculovirus.

PMID- 21716741
TI  - Morphological Integration of the Modern Human Mandible during Ontogeny.
AB  - Craniofacial integration is prevalent in anatomical modernity research. Little
      investigation has been done on mandibular integration. Integration patterns were
      quantified in a longitudinal modern human sample of mandibles. This integration
      pattern is one of modularization between the alveolar and muscle attachment
      regions, but with age-specific differences. The ascending ramus and nonalveolar
      portions of the corpus remain integrated throughout ontogeny. The alveolar region
      is dynamic, becoming modularized according to the needs of the mandible at a
      particular developmental stage. Early in ontogeny, this modularity reflects the
      need for space for the developing dentition; later, modularity is more reflective
      of mastication. The overall pattern of modern human mandibular integration
      follows the integration pattern seen in other mammals, including chimpanzees.
      Given the differences in craniofacial integration patterns between humans and
      chimpanzees, but the similarities in mandibular integration, it is likely that
      the mandible has played the more passive role in hominin skull evolution.

PMID- 21716742
TI  - Before the Emergence of Homo sapiens: Overview on the Early-to-Middle Pleistocene
      Fossil Record (with a Proposal about Homo heidelbergensis at the subspecific
      level).
AB  - The origin of H. sapiens has deep roots, which include two crucial nodes: (1) the
      emergence and diffusion of the last common ancestor of later Homo (in the Early
      Pleistocene) and (2) the tempo and mode of the appearance of distinct
      evolutionary lineages (in the Middle Pleistocene). The window between 1,000 and
      500 thousand years before present appears of crucial importance, including the
      generation of a new and more encephalised kind of humanity, referred to by many
      authors as H. heidelbergensis. This species greatly diversified during the Middle
      Pleistocene up to the formation of new variants (i.e., incipient species) that,
      eventually, led to the allopatric speciation of H. neanderthalensis and H.
      sapiens. The special case furnished by the calvarium found near Ceprano (Italy),
      dated to 430-385 ka, offers the opportunity to investigate this matter from an
      original perspective. It is proposed to separate the hypodigm of a single,
      widespread, and polymorphic human taxon of the Middle Pleistocene into distinct
      subspecies (i.e., incipient species). The ancestral one should be H.
      heidelbergensis, including specimens such as Ceprano and the mandible from Mauer.

PMID- 21716743
TI  - Evolutionary Origins of the Fumonisin Secondary Metabolite Gene Cluster in
      Fusarium verticillioides and Aspergillus niger.
AB  - The secondary metabolite gene clusters of euascomycete fungi are among the
      largest known clusters of functionally related genes in eukaryotes. Most of these
      clusters are species specific or genus specific, and little is known about how
      they are formed during evolution. We used a comparative genomics approach to
      study the evolutionary origins of a secondary metabolite cluster that synthesizes
      a polyketide derivative, namely, the fumonisin (FUM) cluster of Fusarium
      verticillioides, and that of Aspergillus niger another fumonisin (fumonisin B)
      producing species. We identified homologs in other euascomycetes of the Fusarium
      verticillioides FUM genes and their flanking genes. We discuss four models for
      the origin of the FUM cluster in Fusarium verticillioides and argue that two of
      these are plausible: (i) assembly by relocation of initially scattered genes in a
      recent Fusarium verticillioides; or (ii) horizontal transfer of the FUM cluster
      from a distantly related Sordariomycete species. We also propose that the FUM
      cluster was horizontally transferred into Aspergillus niger, most probably from a
      Sordariomycete species.

PMID- 21716744
TI  - Upper Pleistocene Human Dispersals out of Africa: A Review of the Current State
      of the Debate.
AB  - Although there is a general consensus on African origin of early modern humans,
      there is disagreement about how and when they dispersed to Eurasia. This paper
      reviews genetic and Middle Stone Age/Middle Paleolithic archaeological literature
      from northeast Africa, Arabia, and the Levant to assess the timing and geographic
      backgrounds of Upper Pleistocene human colonization of Eurasia. At the center of
      the discussion lies the question of whether eastern Africa alone was the source
      of Upper Pleistocene human dispersals into Eurasia or were there other loci of
      human expansions outside of Africa? The reviewed literature hints at two modes of
      early modern human colonization of Eurasia in the Upper Pleistocene: (i) from
      multiple Homo sapiens source populations that had entered Arabia, South Asia, and
      the Levant prior to and soon after the onset of the Last Interglacial (MIS-5),
      (ii) from a rapid dispersal out of East Africa via the Southern Route (across the
      Red Sea basin), dating to ~74-60 kya.

PMID- 21716745
TI  - Modularity of the oral jaws is linked to repeated changes in the craniofacial
      shape of african cichlids.
AB  - The African cichlids of the East-African rift-lakes provide one of the most
      dramatic examples of adaptive radiation known. It has long been thought that
      functional decoupling of the oral and pharyngeal jaws in cichlids has facilitated
      their explosive evolution. Recent research has also shown that craniofacial
      evolution from radiations in lakes Victoria, Malawi, and Tanganyika has occurred
      along a shared primary axis of shape divergence, whereby the preorbital region of
      the skull changes in a manner that is, relatively independent from other head
      regions. We predicted that the preorbital region would comprise a variational
      module and used an extensive dataset from each lake that allowed us to test this
      prediction using a model selection approach. Our findings supported the presence
      of a preorbital module across all lakes, within each lake, and for Malawi, within
      sand and rock-dwelling clades. However, while a preorbital module was
      consistently present, notable differences were also observed among groups. Of
      particular interest, a negative association between patterns of variational
      modularity was observed between the sand and rock-dwelling clades, a patter
      consistent with character displacement. These findings provide the basis for
      further experimental research involving the determination of the developmental
      and genetic bases of these patterns of modularity.

PMID- 21716746
TI  - Journal of Cardiovascular Disease Research celebrates its anniversary.

PMID- 21716747
TI  - P2Y receptors as regulators of lung endothelial barrier integrity.
AB  - Endothelial cells (ECs), forming a semi-permeable barrier between the interior
      space of blood vessels and underlying tissues, control such diverse processes as
      vascular tone, homeostasis, adhesion of platelets, and leukocytes to the vascular
      wall and permeability of vascular wall for cells and fluids. Mechanisms which
      govern the highly clinically relevant process of increased EC permeability are
      under intense investigation. It is well known that loss of this barrier
      (permeability increase) results in tissue inflammation, the hall mark of
      inflammatory diseases such as acute lung injury and its severe form, acute
      respiratory distress syndrome. Little is known about processes which determine
      the endothelial barrier enhancement or protection against permeability increase.
      It is now well accepted that extracellular purines and pyrimidines are promising
      and physiologically relevant barrier-protective agents and their effects are
      mediated by interaction with cell surface P2Y receptors which belong to the
      superfamily of G-protein-coupled receptors. The therapeutic potential of P2Y
      receptors is rapidly expanding field in pharmacology and some selective agonists
      became recently available. Here, we present an overview of recently identified
      P2Y receptor agonists that enhance the pulmonary endothelial barrier and inhibit
      and/or reverse endothelial barrier disruption.

PMID- 21716748
TI  - Left ventricular structure and function in prediabetic adults: Relationship with
      insulin resistance.
AB  - INTRODUCTION: Several studies have shown that ventricular dysfunction is
      increased in individuals with diabetes. Insulin resistance (IR) may precede type
      2 diabetes, and is a pathogenic factor for it. Furthermore, IR has been shown to
      be an independent predictor of cardiovascular disease in diabetes. Given that
      glucose intolerance and IR precede the development of overt diabetes, these
      factors would be associated with abnormal myocardial performance. AIM OF THE
      WORK: To evaluate the state of left ventricular structure and function in
      prediabetic adults in relation with IR. PATIENTS AND METHODS: A case-control
      study was performed. One hundred and twenty-one consecutive adults with
      prediabetes were enrolled for the study. Forty-two of the adults had IR (group A)
      and 79 had insulin sensitivity (group B). Forty-three healthy (with normal blood
      glucose) adults matched for age and gender were considered as a control group.
      All groups were subjected to full medical history and clinical examination and
      biochemical and echocardiographic studies. RESULTS: There were no statistically
      significant differences between the insulin-sensitive prediabetic group and the
      control group in all parameters of left ventricular structure and systolic and
      diastolic functions. Significant differences were observed between group A and
      control group in the parameters of left ventricular diastolic function (both
      isovolumetric relaxation time and E/A ratio). Regarding correlation between the
      parameters of diastolic function and different variables of IR prediabetic group,
      there was a statistically significant coefficient correlation with HOMA IR, waist
      circumference and triglycerides. No correlation was observed with fasting
      glucose, Hb A1c, body mass index, blood pressure (BP) and total lipids.
      CONCLUSION: In prediabetic adults, IR is associated with impaired left
      ventricular diastolic function, and this association appears to be independent of
      BP, ventricular geometry, glucose tolerance status, total plasma lipids and
      obesity.

PMID- 21716749
TI  - Relationship between ApoE gene polymorphism and coronary heart disease in Gaza
      Strip.
AB  - BACKGROUND: Apolipoprotein E (ApoE) plays a role in the regulation of lipid
      metabolism in humans. ApoE, a 229-amino-acid polypeptide, is classified into
      three major isoforms (E2, E3, and E4) according to the differences in amino acids
      at positions 112 and 158. In the normal population, ApoE3 isoform is the most
      prevalent, and ApoE2 or E4 is frequently associated with hyperlipoproteinemia.
      The objective of this work was to investigate the relationship between ApoE gene
      polymorphism and coronary heart disease (CHD) in Gaza Strip and investigate the
      association between serum lipid levels and CHD. MATERIAL AND METHODS: The study
      population consisted of 137 subjects including 69 CHD cases (45 male, 24 female)
      and 68 healthy subjects (33 male and 35 female). RESULTS: The ApoE3/E3 genotype
      was the most common in the control and the CHD groups. ApoE2/E3 and ApoE3/E4 were
      the next most common genotypes. The frequencies of ApoE alleles in the CHD
      subjects were 0.826 for E3, 0.137 for E4, and 0.0362 for E2. These frequencies
      are comparable to those found in the control group which were 0.875 for the E3,
      0.073 for E4, and 0.0515 for E2. No statistically significant differences in ApoE
      genotypes were found between the patients and the control groups. Moreover, there
      was no significant difference between the mean of triglyceride (TG) and HDL
      levels among different ApoE genotypes. However, there was a significant
      difference in the mean of LDL and ApoE genotypes where the mean of LDL was 218.17
      mg/dl in ApoE4, 149.67 mg/dl in ApoE2, and 184.52 mg/dl in ApoE3. A significant
      difference was also evident between the mean of LDL levels in the CHD and the
      control group where the mean of LDL was 126 mg/dl in CHD and 111.47 mg/dl in the
      control group. Our study indicated that there was no significant difference
      between the mean of cholesterol and TG levels of the CHD and the control groups.
      CONCLUSIONS: To our knowledge, this is the first study in Gaza Strip
      investigating the relation between ApoE genotypes and CHD. Further investigations
      are needed to link other genetic factors to CHD.

PMID- 21716751
TI  - Clinical efficacy of percutaneous renal revascularization with stent placement in
      hypertension among patients with atherosclerotic renovascular diseases.
AB  - AIM: The aim was to assess the effect of renal angioplasty with stent on
      systolic, diastolic, and mean arterial blood pressure (MAP) in awake and sleep
      time with ambulatory blood pressure (ABP) monitoring (Holter monitoring).
      MATERIALS AND METHODS: Patients with angiographically proven atherosclerotic
      renal artery stenosis (RAS) were referred to the Angiography Department of Imam
      Hospital for intervention during a 1-year period from June 2008 to December 2009.
      Primary stent placement was attempted by a single operator in 27 severe RAS cases
      although 1 case was omitted from the study because of technical failure. Pre- and
      postprocedure creatinine levels, ejection fraction (EF), history of diabetes
      mellitus (DM), and ABP were obtained. Twenty-six (17 men, 9 women; average age,
      62.6 years; age range, 90-21 years) consecutive patients participated in the
      study. RESULTS: All patients had severe hypertension resistant to multiple
      medications; 10 patients had impaired renal function (serum creatinine level
      greater than 130 umol/L). A total of 3 (11.5%) patients had congestive heart
      failure, and 10 (37.7%) were diabetic. Hypertension was cured in 1 (4%) patient,
      had improved in 23 (88.4%) patients, and had failed to respond to treatment in 2
      (7.6%). Serum creatinine decreased significantly from 1.46 +/- 0.89 to 1.35 +/-
      0.61 mg/dL (P<0.05). CONCLUSION: Percutaneous transluminal angioplasty for
      atheromatous RAS rarely cures hypertension, but improved blood pressure control
      is often achieved.

PMID- 21716750
TI  - Mesenchymal stromal cells for cardiovascular disease.
AB  - The fields of regenerative medicine and cellular therapy have been the subject of
      tremendous hype and hope. In particular, the perceived usage of somatic cells
      like mesenchymal stromal cells (MSCs) has captured the imagination of many. MSCs
      are a rare population of cells found in multiple regions within the body that can
      be readily expanded ex vivo and utilized clinically. Originally, it was
      hypothesized that transplantation of MSCs to sites of injury would lead to de
      novo tissue-specific differentiation and thereby replace damaged tissue. Now, it
      is generally agreed that MSC home to sites of injury and direct positive
      remodeling via the secretion of paracrine factors. Consequently, their clinical
      utilization has largely revolved around their abilities to promote
      neovascularization for ischemic disorders and modulate overly exuberant
      inflammatory responses for autoimmune and alloimmune conditions. One of the major
      issues surrounding the development of somatic cell therapies like MSCs is that
      despite evoking a positive response, long-term engraftment and persistence of
      these cells is rare. Consequently, very large cell doses need be administered for
      raising production, delivery, and efficacy issues. In this review, we will
      outline the field of MSC in the context of ischemia and discuss causes for their
      lack of persistence. In addition, some of the methodologies be used to enhance
      their therapeutic potential will be highlighted.

PMID- 21716752
TI  - Association of statin therapy with blood pressure control in hypertensive
      hypercholesterolemic outpatients in clinical practice.
AB  - BACKGROUND: Some clinical evidence revealed that statins, apart from lowering
      cholesterol levels, also have an antihypertensive effect. Our aim was to evaluate
      the existence of a possible association of statin therapy with blood pressure
      (BP) control in clinical practice. MATERIALS AND METHODS: Patients attending a
      hypertension/dyslipidemia clinic were prospectively evaluated. Those patients
      with a diagnosis of stage 1 hypertension and hypercholesterolemia who consented
      to participate were included in the study, either in the statin group (when
      taking a statin) or in the control group (when not taking a statin). Exclusion
      criteria included dementia, pregnancy, or breastfeeding, and history or evidence
      of stage 2 hypertension. Detailed clinical information was prospectively obtained
      from medical records. A total of 110 hypertensive patients were assigned to the
      study (82 in the statin group and 28 in the control group). RESULTS: Although
      there were no significant differences (P > 0.05) in both groups concerning
      gender, body mass index, antihypertensive pharmacotherapy, and serum levels of
      high-density lipoprotein cholesterol and triglycerides, a higher BP control was
      observed in the statin group (P = 0.002). Significantly lower systolic BP (-6.7
      mmHg, P = 0.020) and diastolic BP (-6.4 mmHg, P = 0.002) levels were reported in
      the statin group. Serum levels of low-density lipoprotein were also significantly
      lower in the statin group (P < 0.001). CONCLUSIONS: This observational study
      detected an association of statin therapy with BP control in hypertensive
      hypercholesterolemic patients in clinical practice. These findings raise the
      possibility that statin therapy may be useful for BP control in the studied
      population.

PMID- 21716753
TI  - Comparison of left ventricular mass in normotensive type 2 diabetes mellitus
      patients with that in the nondiabetic population.
AB  - Cardiovascular disease is increased in individuals with type 1 or type 2 diabetes
      mellitus (DM). Left ventricular hypertrophy (LVH), which is an ominous prognostic
      sign and an independent risk factor for cardiac events, is often present in type
      2 DM patients. The aim of our cross-sectional study was to evaluate the
      prevalence of LVH, and risk factors for its development, in normotensive type 2
      diabetic patients without antihypertensive medication. The objectives of the
      study were to find out the prevalence of high left ventricular mass (LVM) in
      normotensive type 2 diabetic patients and compare it with nondiabetics and to
      uncover the risk factors for the development of high LVM in normotensive type 2
      diabetic patients. A total of 130 age- and sex-matched subjects were selected (65
      cases, diabetic normotensive, and 65 controls, nondiabetic normotensive) and
      baseline data were collected. LVM and left ventricular mass index (LVMI) were
      calculated using echocardigraphic parameters and body surface area. LVMI was
      significantly higher in patients with type 2 DM compared with age-, sex-matched
      healthy population (104.9 +/- 21 vs. 78.5 +/- 22.7 g/m(2), respectively; P <
      0.05). BMI, HbA1c, and duration of diabetes were significantly associated with
      LVH whereas sexes, age, PPBS, were not.

PMID- 21716754
TI  - Evaluation of correlation between oxidative stress and abnormal lipid profile in
      coronary artery disease.
AB  - BACKGROUND: Coronary artery disease (CAD) is the most common cause of sudden
      death, none and death of men and women over 20 years of age. The aim of the study
      was to know if there is any linear correlation between oxidants and abnormal
      lipid profile parameters in CAD. MATERIALS AND METHODS: The present study
      includes 42 known CAD cases (age = 41-75 years) and 33 age- and sex-matched
      healthy controls. Malondialdehyde ( MDA), total cholesterol, high-density
      lipoprotein (HDL) cholesterol, and triacylglyceride were measured and low-density
      lipoprotein (LDL) cholesterol was calculated in both cases and controls,
      respectively. RESULTS: MDA was significantly increased in cases than controls (P
      = 0.0000001). Total cholesterol was high in cases than controls (P = 0.0000001).
      HDL cholesterol was significantly decreased in cases than controls (P =
      0.0000001). LDL cholesterol was high in cases than controls (P = 0.0000001).
      Triacylglyceride was high in cases than controls (P = 0.0000001). Insignificant
      positive correlation were observed between MDA and total cholesterol (r = 0.258),
      between MDA and LDL cholesterol (r = 0.199), and between MDA and HDL cholesterol
      (r = 0.134). Negative correlation was observed between MDA and triacylglyceride
      (r = -0.314). CONCLUSION: Increased oxidative stress and abnormal lipid profile
      were observed in CAD cases. Our study showed that statistically significant
      linear relationship could not be established between increased oxidative stress
      and abnormal lipid profile parameters, suggesting that increased oxidative stress
      and abnormal lipid profile are two independent risk factors in the pathomechanism
      of atherogenesis.

PMID- 21716755
TI  - Obesity measures, metabolic profiles, blood pressure and intake of dietary fatty
      acids in rural women of Asian Indian origin: Santiniketan women study.
AB  - OBJECTIVES: The present cross-sectional study was aimed to investigate obesity
      measures, metabolic profiles, blood pressure, and intake of dietary fatty acids
      in rural women of Asian Indian origin. MATERIALS AND METHODS: A total of 280
      healthy rural women aged 25-65 years took part in the study. A random sampling
      procedure using a local voters' registration list was followed to select the
      participants. All participants belonged to the Bengalee population and were
      inhabitants of the Bolpur-Santiniketan area, West Bengal, India. Anthropometric
      measures, namely, height, weight, circumferences of waist and hip, skinfolds at
      biceps, triceps, subscapular, and suprailiac regions, etc., were collected using
      standard techniques. Body mass index (BMI), percentages of body fat (PBFs), basal
      metabolic rate (BMR), and intra-abdominal visceral fat (IVF) were measured using
      an Omron body fat analyzer (Omron Corporation, Tokyo, Japan). Fat mass (FM), fat
      free mass (FFM), waist-hip ratio (WHR), and sum of four skinfolds (SF4) were also
      taken into consideration. Blood pressure and metabolic and hormonal profiles were
      measured using standard techniques. The weekly consumption (frequency) of food
      stuffs was collected using an already validated food frequency schedule. RESULTS:
      The result showed that the mean age was 41.52 +/- 10.95, BMI 23.07 +/- 4.34, PBF
      31.76 +/- 7.06, BMR 1162.34 +/- 139.59, WHR 0.83 +/- 0.06, systolic blood
      pressure 118.84 +/- 20.35, diastolic blood pressure 77.77 +/- 12.12, total
      cholesterol 185.61 +/- 25.19, triglyceride level 135.82 +/- 30.39, high-density
      lipoprotein 48.13 +/- 6.13, low-density lipoprotein 109.90 +/- 22.53, fasting
      blood glucose 90.91 +/- 7.98, and insulin 11.98 +/- 3.42. The result also shows
      the mean intake of total protein to be 177.01 +/- 47.79, total energy 8321.60 +/-
      1354.86, total fat 210.36 +/- 53.57, total PUFA 82.02 +/- 49.73, and total MUFA
      94.01 +/- 16.38. The percentile distribution of the dietary fat intake revealed
      that the 10th and 95th percentile values of the total protein intake were 125.3
      and 261.5, total energy intake were 7491.6 and 10470.2, total fat intake were
      178.8 and 273.5, total PUFA intake were 55.5 and 191.7, and of the total MUFA
      intake were 86.0 and 126.9, respectively. CONCLUSION: It seems reasonable to
      argue that dietary management including dietary guidelines across India is
      essential to retard the growing incidence of cardiovascular diseases in coming
      years.

PMID- 21716756
TI  - Recurrent strokes under anticoagulation therapy: Sticky platelet syndrome
      combined with a patent foramen ovale.
AB  - The sticky platelet syndrome (SPS) is a congenital disorder characterized by
      platelet hyperaggregability to epinephrine and/or adenosine diphosphate; this
      predisposes affected individuals to acute myocardial infarction, ischemic optic
      neuropathy, recurrent venous thromboembolism, and transient ischemic cerebral
      attacks and strokes. Here, we describe an unusual case with recurrent
      cerebrovascular accidents due to SPS, in the presence of a patent foramen ovale
      (PFO). We report an unusual case of a 56-year-old female patient with a PFO, who
      suffered from recurrent strokes despite long-term medication with clopidogrel for
      SPS. The patient underwent successful transcatheter closure of the PFO, and, in
      addition, she has been placed on low-dose acetylsalicylic acid. After 18-month
      follow-up, she demonstrated an intact atrial septum without any vegetations on
      the percutaneous device until today. She has had no further thromboembolic
      events.

PMID- 21716757
TI  - Infective endocarditis presents as isolated splenomegaly.
AB  - Sub acute left-sided bacterial endocarditis is a serious condition that may be
      overlooked due to highly variable clinical manifestations. We present the case of
      a 45-year-old man who presented with complaints of fullness in his abdomen and
      splenomegaly that referred to the surgery clinic. He underwent diagnostic
      splenectomy. 3 month after splenectomy endocarditis was diagnosed. We recommend
      echocardiography in the work up of isolated splenomegaly.

PMID- 21716758
TI  - A case of arrythmogenic right ventricular cardiomyopathy in a middle-aged woman.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of heart muscle
      disease characterized by the gradual replacement of the right ventricular
      myocardium with fibrous tissue and fat. It could be the major cause of sudden
      cardiac death with ventricular tachycardia, and there is a variation in the
      history of the disease. We reported an unusual case of ARVC in a middle-aged
      woman with congestive heart failure as her first presentation for a long time.

PMID- 21716759
TI  - Extremely rare case of a rupture of the left sinus of Valsalva aneurysm into the
      main pulmonary artery.
AB  - We describe a case of ruptured aneurysm of the left coronary sinus of Valsalva
      diagnosed by transthoracic two-dimensional echocardiography. A very few cases
      with ruptured left sinus of Valsalva have been reported. We are reporting a
      rupture of the left sinus of Valsalva into the main pulmonary artery in a 40-year
      old male diagnosed by transthoracic echocardiography.

PMID- 21716760
TI  - Mycobacterium abscessus bacteremia in an immunocompetent patient following a
      coronary artery bypass graft.
AB  - Sternal osteomyelitis with bacteremia due to Mycobacterium abscessus is rarely
      seen in immunocompetent hosts. Routine pyogenic cultures in these cases are often
      negative causing a delay in diagnosis and treatment. Clinicians and
      microbiologists should rule out the possibility of infection due to
      nontuberculous mycobacteria while managing cases of nonhealing culture-negative
      wounds with conventional antibiotic therapy. We report a case of bacteremia
      secondary to a nonhealing sternal wound due to M. abscessus. A combination of
      radical debridement and prolonged antimicrobial therapy helped in the complete
      eradication of the infection.

PMID- 21716761
TI  - Lipoleiomyoma of uterus in a postmenopausal woman.
AB  - Lipoleiomyomas are uncommon benign neoplasms of uterus and are considered to be a
      variant of uterine myomas. Their reported incidence varies from 0.03 to 0.2%.
      Lipoleiomyoma consists of variable proportion of mature lipocytes and smooth
      muscle cells. These tumors generally occur in asymptomatic obese perimenopausal
      or menopausal women. We report this case of uterine lipoleiomyoma because of its
      rarity.

PMID- 21716762
TI  - The ongoing nosologic dilemma with the metabolic syndrome.

PMID- 21716763
TI  - Normal BMD values for Indian females aged 20-80 years.
AB  - BACKGROUND: Dual-energy X-ray absorptiometry is presently considered the gold
      standard for measuring bone mineral density (BMD). The International Osteoporosis
      Foundation and World Health Organization have recommended National Health and
      Nutrition Examination Survey III database values for women aged 20-29 years to be
      followed as reference BMD values worldwide. However, the BMD may differ for
      different populations. OBJECTIVE: The objective of the present study was to plot
      BMD values in the hip (neck) and lumbar spine (L1-L4 AP view) in Indian women
      aged 20-80 years. Also, BMD values in the 20-60-year-old females were compared
      with reference American/European population. RESULT: It was found that the BMD of
      Indian females was 1.5-2 standard deviation (SD) s lower than that of the
      reference Western population in all the comparative age groups. CONCLUSION: It is
      reasonable to conclude that BMD values of the hip and spine among comparative
      Indian and Western female age groups show significant differences. Hence,
      different normals should be followed for each population.

PMID- 21716765
TI  - Editor'S comment.

PMID- 21716764
TI  - Acute abdomen with hemoperitoneum in a postmenopausal woman.
AB  - Gynecological emergencies may be encountered in postmenopausal ladies like that
      of ruptured ectopic pregnancy in the reproductive age group. We report a case of
      ruptured granulosa cell tumor in a 70-year-old woman who presented with acute
      abdomen and hemoperitoneum.

PMID- 21716766
TI  - Effective risk assessment tools for osteoporosis in the Indian menopausal female.
AB  - OBJECTIVES: This study was designed to assess the effectiveness of self
      administered osteoporosis risk score sheet, body mass index (BMI), and bone
      mineral density (BMD) (ultrasound) in screening females with low bone mass, and
      how the results of the tools correlate with each other. MATERIALS AND METHODS:
      The study was conducted on 536 postmenopausal women, who attended public
      awareness camps on Midlife Women Health held at the Menopause Research Unit,
      MGMCH, Sitapura, Jaipur. At these camps, in addition to several informational
      sessions on issues related to menopause, ultrasonic measurement of BMD was
      conducted on each participant. A broad questionnaire to identify midlife health
      problems was developed, and osteoporosis specific score sheet was designed to be
      self-administered. Patients were required to complete the osteoporosis specific
      risk score sheet and women health questionnaire (WHQ). BMI was determined.
      Statistical analysis was carried out to find the correlation between various
      variables. Sensitivity and specificity of the each risk score ascertained and
      cutoff risk score for identifying osteopenia was derived by comparing area under
      curve of each risk score on drawing receiver operational curve (ROC). RESULTS:
      Sensitivity of risk score system was calculated to be 78.33% with 95% confidence
      interval being 73.24-82.86% and specificity was 27.12% with 95% confidence
      interval being 21.56-33.27%, keeping the cutoff point at nine. There was
      statistically significant inverse relationship between risk score and BMD values
      with Pearson correlation coefficient of (-) 0.22 and positive relationship
      between BMD and BMI with correlation coefficient of 0.192. CONCLUSION: By noting
      down the risk factors and BMI, we can screen out the women who require further
      evaluation and management, thus, it is an effective tool, particularly in
      developing countries like India, where most of the patients cannot afford
      expensive DEXA scans, although considered as the gold standard for BMD
      assessment. With the help of such scoring systems, health resources can be
      judiciously utilized.

PMID- 21716767
TI  - Bone mineral density and reference standards for Indian women.

PMID- 21716768
TI  - Synopsis of results from European male ageing study.

PMID- 21716769
TI  - Attitudes and practices of gynecologists in Jaipur toward management of
      menopause.
AB  - BACKGROUND: In earlier days, hormone replacement therapy (HRT) was recommended
      for menopause symptoms and also gained much popularity. However, the Women's
      Health Initiative (WHI) studies suggested an increased risk of cardiovascular and
      Alzheimer's disease. These findings led to a dramatic decrease in hormone therapy
      (HT) prescriptions all over the world. However, the WHI conclusions remain
      debatable especially because of contradictory results from antecedent studies.
      Inspite of these controversies, post-WHI, most gynecologists refrain from
      prescribing MHT (menopausal hormone replacement therapy, MHT). Furthermore, many
      Indian gynecologists prefer to prescribe alternative treatments that would help
      alleviate symptoms and thus avoid HRT. We decided to carry out a survey and
      document the current opinions regarding indications of HRT and alternative
      therapies and prescribing practices of Jaipur-based gynecologists. OBJECTIVE:
      This study was designed to find out the current attitudes and practices of
      gynecologists (Jaipur) towards management of menopause. MATERIALS AND METHODS: A
      questionnaire concerning attitudes, management strategies, and use of HT was
      mailed out to gynecologists, and they are asked to complete the questionnaire.
      Data were analyzed using the total number of respondents (n = 321). The results
      were analyzed using a simple percentage method as this was most suitable for this
      kind of studies. RESULTS: From the results, 69.04% gynecologists were currently
      prescribing MHT. Hot flashes were the most common indication for MHT
      prescriptions and 78.57% were familiar with controversies surrounding WHI study.
      Also, 61.9% would consider using MHT for themselves. Alternative therapy was
      adopted by 83.48% in their prescribing practice. The reason cited by 71% for
      preferring alternative therapies was that it was safer and less controversial.
      CONCLUSIONS: The prescribing practices of Jaipur gynecologists in lieu of ongoing
      controversies surrounding HT have shifted and now also support alternative
      therapies for menopause management. In this era of phasic prescriptions, for
      immediate relief of hot flashes and mood swings, MHT was favored. However, for
      long-term management of women with poor compliance, alternative therapies were
      considered a safer option.

PMID- 21716770
TI  - Menopause and metabolic syndrome: A study of 498 urban women from western India.
AB  - INTRODUCTION: Metabolic syndrome (MS) is a cluster of risk factors for future
      development of type 2 diabetes mellitus and cardiovascular diseases. Menopausal
      transition with its incidental hormonal changes is considered to contribute to
      the development of MS. However, age is known to influence MS risk factors.
      OBJECTIVE: The present study explores the prevalence of MS in pre- and
      postmenopausal women from western India. METHODS: Four hundred and ninety eight
      women above 35 years of age, participating in women's health care program were
      assessed for the prevalence of MS using two criteria- International Diabetes
      Federation criteria (IDF) and Harmonization (H_MS) criteria. RESULTS: Prevalence
      of MS amongst postmenopausal women was significantly higher (P < 0.001) than that
      in premenopausal women by both, IDF (premenopausal 45% and postmenopausal 55%)
      and H_MS criteria (premenopausal 44% and postmenopausal 56%). However, this
      significance disappeared when data was adjusted for the confounding variable of
      age.

PMID- 21716771
TI  - Diligent case reports: A rich reservoir for midlife healthcare and research.

PMID- 21716772
TI  - Calcium supplementation: Cardiac woes.

PMID- 21716773
TI  - Yoga and menopausal transition.
AB  - With increased life expectancy, today, women spend one-third of their life after
      menopause. Thus more attention is needed towards peri- and post-menopausal
      symptoms. Estrogen replacement therapy is the most effective treatment, however,
      it has its own limitations. The present need is to explore new options for the
      management of menopausal symptoms. Yogic life style is a way of living which aims
      to improve the body, mind and day to day life of individuals. The most commonly
      performed Yoga practices are postures (asana), controlled breathing (pranayama),
      and meditation (dhyana). Yoga has been utilized as a therapeutic tool to achieve
      positive health and control and cure diseases. The exact mechanism as to how Yoga
      helps in various disease states is not known. There could be neuro-hormonal
      pathways with a selective effect in each pathological situation. There have been
      multiple studies that have combined the many aspects of Yoga into a general Yoga
      session in order to investigate its effects on menopausal symptoms. Integrated
      approach of Yoga therapy can improve hot flushes and night sweats. There is
      increasing evidence suggesting that even the short-term practice of Yoga can
      decrease both psychological and physiological risk factors for cardiovascular
      disease (CVD). Studies conclude that our age old therapy, Yoga, is fairly
      effective in managing menopausal symptoms.

PMID- 21716774
TI  - Non-conventional hormone therapy - Tissue-specific Tibolone-Caution.
AB  - OBJECTIVES: The present retrospective study was undertaken to assess safety
      profile of long term Tibolone therapy when one of my patients developed carcinoma
      breast. METHODS: Fifty patients who were put on Tibolone were studied as regards
      the indication for Tibolone therapy, age distribution, duration of therapy and
      side effects. RESULTS: Although most subjects responded well to therapy without
      significant side effects two patients developed breast lump. One of the breast
      lumps was malignant, the other benign. It is possible that prolonged Tibolone
      therapy may have caused carcinoma breast as against the notion that Tibolone is
      breast protective. Few of recent studies like Million Women Study and LIBERATE
      study which was concluded in April 2010, have shown that Tibolone also increases
      risk of carcinoma breast. CONCLUSION: Tibolone when used for management of
      menopausal symptoms should be given for less than 4 years and regular follow up
      with mammography is must.

PMID- 21716775
TI  - Effect of acute moderate exercise on cognitive event-related potentials n100,
      p200, n200, and interpeak latencies.
AB  - BACKGROUND: Effect of acute moderate exercise on cognition has been studied
      recently, although there are controversial reports in this context. This is the
      reason we performed this study, to observe the effect of acute moderate exercise
      on the cognitive functions of persons having a sedentary lifestyle, by measuring
      the latencies of event-related potentials N100, P200, N200, and the inter-peak
      latencies N100-P200, P200-N200, and N200-P300. MATERIALS AND METHODS: Sixty right
      handed participants (34 males, 26 females) of age group 15 - 30 years, having a
      sedentary lifestyle, were recruited for the study. A baseline recording of event
      related potentials was conducted and then they were subjected to acute moderate
      exercise (60 - 80% of the maximum load of effort during exercise, where 100%=200 
      Age), again the recording was carried out using the paired student's 't' test,
      to compare the present values with the initial values. RESULTS: After performing
      the exercise there was a significant decrease in the latency of wave N1 and P2 of
      females for both frequent and rare stimuli. A significant decrease in the latency
      was seen in wave N2 with rare stimulus in both females and males. While, for
      frequent stimulus a significant decrease was seen only in females. Also the N2-P3
      interpeak latency significantly decreased in males, while there was no
      significant decrease in females. CONCLUSION: There was a definite role of
      exercise in enhancing the cognitive functions as evidenced by its effect on the
      latencies of event-related potentials N100, P200, N200, and interpeak latencies.

PMID- 21716776
TI  - Effects of picture exchange communication system on communication and behavioral
      anomalies in autism.
AB  - Communication skills deficits and stereotyped behaviors are frequently found
      among people with pervasive developmental disabilities like autism. These
      communication and behavioral oddities of autism are often considered to be
      difficult to treat and are challenging. Picture exchange communication system
      (PECS) is a six-phase picture system based on applied behavior analysis and is
      specially designed to overcome these communication difficulties in children with
      autism by encouraging the child to be the communication initiator. The present
      paper throws light on the process of using PECS along with other traditional
      behavioral approaches in managing communication deficits and behavioral
      stereotypies in a seven-year-old male child diagnosed as having childhood autism.
      The identified target behaviors of repeated head turning, flapping his hands,
      poor communication skills were assessed using various rating scales including
      visual analogue scale as per clinician observation and parental reports and
      managed using PECS as an adjunct to traditional behavioral techniques of
      contingency management, differential reinforcement, task direction and reprimand.
      Outcome was assessed using same tools after thirty-two sessions of interventions
      spread over three months. Significant improvements of around 60% were observed in
      the target behaviors.

PMID- 21716777
TI  - Work-Life Balance among Married Women Employees.
AB  - Family-work conflict (FWC) and work-family conflict (WFC) are more likely to
      exert negative influences in the family domain, resulting in lower life
      satisfaction and greater internal conflict within the family. Studies have
      identified several variables that influence the level of WFC and FWC. Variables
      such as the size of family, the age of children, the work hours and the level of
      social support impact the experience of WFC and FWC. However, these variables
      have been conceptualized as antecedents of WFC and FWC; it is also important to
      consider the consequences these variables have on psychological distress and
      wellbeing of the working women. AIM: to study various factors which could lead to
      WFC and FWC among married women employees. MATERIALS AND METHODS: The sample
      consisted of a total of 90 married working women of age between 20 and 50 years.
      WFC and FWC Scale was administered to measure WFC and FWC of working women. The
      obtained data were analyzed using descriptive and inferential statistics. Carl
      Pearson's Correlation was used to find the relationship between the different
      variables. FINDINGS AND CONCLUSION: The findings of the study emphasized the need
      to formulate guidelines for the management of WFCs at organizational level as it
      is related to job satisfaction and performance of the employees.

PMID- 21716778
TI  - Study of the effect of nortriptyline and fluvoxamine on psychomotor functions in
      healthy volunteers.
AB  - BACKGROUND: Today, many antidepressants are available, but they often cause
      adverse effects, particularly psychomotor and cognitive. It leads to patient
      maladjustment and may impair psychomotor performance. Fluvoxamine is a newer
      antidepressant and hence the present study was planned to investigate its effect
      on psychomotor functions and compare with nortriptyline and record their adverse
      reactions. MATERIALS AND METHODS: A total of 26 healthy volunteers were included
      in this double-blind, placebocontrolled, crossover study. Single oral doses of
      fluvoxamine 50 mg, nortriptyline 50 mg and placebo were administered following a
      Latin square design. The objective parameters-six digit cancellation test, digit
      symbol substitution test, critical flicker fusion test, arithmetic ability test,
      hand steadiness test and subjective parameters such as visual analogue scale 1,
      2, 3 were tested at 0, 2 and 4 h. The side-effects were also investigated.
      RESULTS: Nortriptyline impaired all subjective and objective psychomotor
      functions while fluvoxamine did not show any significant effect on objective
      tests. However, on subjective parameters, there was a significant effect. The
      side-effects observed were dryness of mouthwith the nortriptyline and nausea and
      headache with fluvoxamine. CONCLUSION: Fluvoxamine is a better antidepressant
      drug in comparison with nortriptyline as it causes a less impairment of
      psychomotor functions.

PMID- 21716779
TI  - Psychiatric curriculum and its impact on the attitude of Indian undergraduate
      medical students and interns.
AB  - CONTEXT: Psychiatry is given very less importance in the Indian undergraduate
      medical curriculum and this affects the attitudes of students toward psychiatry
      and mentally ill patients. AIM: To study the attitude of undergraduate medical
      students and interns toward psychiatry and mentally ill patients. MATERIALS AND
      METHODS: Undergraduate medical students and interns of a private medical college
      and research institute in South India consented to form our sample. We studied
      the General Health Questionnaire, overall level of satisfaction in ongoing
      Medical course using Visual Analog Scale, attitudes toward psychiatry scale and
      the attitudes toward mentally ill patient's scale of the students, with their
      informed consent. SPSS version 18 was used for analysis of data. RESULTS:
      Participation rate was 96%. Mean age of entire sample was 20.56 years. The total
      mean score on the General Health Questionnaire was 13.52 in first year but became
      worse toward internship (18.2). The level of satisfaction in the medical course
      dipped from 86% at baseline to 20% during internship. Equally high scores were
      noted in the attitude toward mentally ill scale. On the attitude toward
      psychiatry scale, there were more views on psychiatry as being an unscientific
      specialty, psychiatrists being considered poor role models, and psychiatric
      teaching was of low quality and psychiatry was the least preferred career choice.
      CONCLUSIONS: The undergraduate medical students have a very unfavorable attitude
      toward psychiatry and mentally ill patients.

PMID- 21716780
TI  - Benzodiazepines misuse: the study community level Thailand.
AB  - CONTEXT: Benzodiazepines (BZD) misuse, abuse, and dependence are becoming a new
      problem in medicine, in Thailand, and the pharmacoepidemiology knowledge is
      insufficient. The aim of this study is to estimate the prevalence of
      benzodiazepine use, misuse, abuse, and dependence in the general population of
      the Ubon Rachathani province, in Thailand. AIMS: To estimate the prevalence of
      benzodiazepine use, misuse, abuse, and dependence in the general population.
      SETTINGS AND DESIGN: The cross-sectional household survey research was conducted
      from October 2008 to June 2009, with a target population age of 15 years and
      above. This took place in Ubon Ratchathani Province, in Thailand. MATERIALS AND
      METHODS: A total sample size of 2280 were selected from three-stage stratified
      random sampling. BZD were identified with an accuracy of generic name, trade
      name, and drug characteristics. The DSM-IV questionnaire was used to define
      misuse, abuse, and dependence. The accuracy of dependence was interpreted with
      the help of the judgment of a psychiatric nurse. STATISTICAL ANALYSIS: For the
      statistical analyses, prevalence was estimated with weight adjustment, variances
      estimated by the Teylor Series Linearization method, and interpreted with 95%
      confidence interval (CI). RESULTS: There were 46,805 current users [3.9% (95% CI:
      2.2-6.4)], 26,404 misusers [2.2% (95% CI: 1.6-6.2)], 7,203 abusers [0.6% (95% CI:
      0.1 - 4.1)], and 2,402 with dependence [0.2% (0.1-9.2)]. When considering the
      group of current users in this study, 57.2% misusers, 16.6% abusers, and 5.9%
      with dependence were found, respectively. CONCLUSIONS: All prevalence of use was
      higher than previously reported, in Thailand, while more than half of the current
      users had a behavior of misuse. Surveillance of misuse should be undertaken in
      the current use. The medical professional should counsel the patient on the harm
      of misuse and limit the amount of medicine, with necessary dispensing.

PMID- 21716781
TI  - Coping Styles, Stress Tolerance, and Wellbeing and their Correlations in the
      Women Spouses of the Mentally Ill.
AB  - BACKGROUND: In the Indian cultural scenario, the wife is the primary caregiver
      when the husband falls mentally sick. The caregiver burden and the gender issues
      make women more vulnerable to this particular situation. This study attempts to
      take a closer look at the coping styles, stress tolerance, and wellbeing of such
      a population and the interplay of the above variables. AIM: This study aims to
      determine correlations between coping styles, stress tolerance, and wllbeing of
      the women spouses of the mentally ill. MATERIALS AND METHOD: A passive
      observational design has been used. The tools used in this study are Life Change
      Event Inventory, AECOM Coping Scale Questionnaire, and PGI Well being scale.
      STATISTICAL ANALYSIS: Pearson's product moment correlation is used to study the
      relationship between the variables. RESULT AND CONCLUSIONS: It is concluded that
      the wives of mentally ill tend to use certain coping styles more than others and
      this preference lowers the stress experienced and enhance their sense of well
      being. It is also concluded that women with mentally ill spouses could be hardier
      due to the sociocultural expectations imposed on them where care giving of their
      mentally sick husbands are concerned.

PMID- 21716783
TI  - Recognition of the kind of stress coping in patients of multiple sclerosis.
AB  - BACKGROUND: Investigations have shown that some factors like stress can increase
      the recurrence and severity of multiple sclerosis (MS). Considering the direct
      influences of depression and anxiety on our body immunity system, and also the
      relation between stress and factors, such as Insulin Growth Factor (IGF-1),
      involved in neurogenesis and myelin repairing, it is an essential issue to
      identify the most common method used in relieving stress by such patients.
      OBJECTIVE: To identify the type of common coping methods for stressful situation.
      MATERIALS AND METHODS: This case-control study was performed on 50 patients of
      both the genders with MS in Esfahan (Esfahan MS Association). The data were
      collected and then analyzed using analysis of variance (ANOVA) method with the
      help of SPSS software version 15. P value less than 0.05 was considered as
      statistically significant. RESULTS: In our study, coping method for stressful
      situation was significantly different in MS patients versus the healthy group
      (P=0.02). Descriptive indices showed that these patients use avoidant method more
      commonly than the control group (mean=45.01, SD=8.9 vs. mean=40.8, SD=11.8,
      respectively). CONCLUSION: Due to the different methods used by MS patients to
      cope with stressful situation in comparison with the healthy ones, more
      appropriate techniques can be introduced to modify them, and hence, less stress
      induced side effects could be expected in this population.

PMID- 21716782
TI  - Functional neuro-imaging and post-traumatic olfactory impairment.
AB  - OBJECTIVE: To evaluate via a research literature survey the anterior neurological
      significance of decreased olfactory functioning following traumatic brain
      injuries. MATERIALS AND METHODS: A computer literature review was performed to
      locate all functional neuro-imaging studies on patients with post-traumatic
      anosmia and other olfactory deficits. RESULTS: A convergence of findings from
      nine functional neuro-imaging studies indicating evidence for reduced metabolic
      activity at rest or relative hypo-perfusion during olfactory activations. Hypo
      activation of the prefrontal regions was apparent in all nine post-traumatic
      samples, with three samples yielding evidence of reduced activity in the temporal
      regions as well. CONCLUSIONS: The practical ramifications include the reasonable
      hypothesis that a total anosmic head trauma patient likely has frontal lobe
      involvement.

PMID- 21716784
TI  - First episode mania at 75 years of age.
AB  - Late onset psychiatric disorders are often associated with organic factors,
      either medical or neurological. Mania occurring for the first time in the elderly
      population is rarely reported. We hereby report a patient with first episode
      mania who was investigated in detail, but no organic factors were found. He was
      diagnosed as first episode mania and was managed with divalproex and olanzapine.

PMID- 21716785
TI  - Circumcision.
AB  - Circumcision is one of the oldest and the most controversial surgical procedures
      performed worldwide and is almost universal among Muslim and Jewish men. Most
      medical institutions in various countries agree that although there may be health
      benefits, there is no medical justification for routine circumcision in neonates
      or children. It should be performed only for established medical reasons and
      should not be universally recommended. There are modern techniques that provide
      safer, simpler, quicker, and cheaper alternatives to the traditional means of
      circumcision with good functional and cosmetic results. Female genital mutilation
      (FGM) includes procedure that alters or injures female genital organs for
      nonmedical reasons. Various degrees of FGM are prevalent, the most mutilating one
      being infibulation. There are numerous gynecologic and obstetrical complications
      with infibulation. FGM also plays a significant role in facilitating the
      transmission of HIV infection through numerous mechanisms. Health care providers
      have an important role to play in the eradication of this practice. Increased
      professional and public awareness about such a practice is required.

PMID- 21716786
TI  - Screening of pregnant women attending the antenatal care clinic of a tertiary
      hospital in eastern Saudi Arabia for Chlamydia trachomatis and Neisseria
      gonorrhoeae infections.
AB  - INRODUCTION: Of the "top ten" sexually transmitted infections, Chlamydia
      trachomatis and Neisseria gonorrhoeae are ranked second and fifth, respectively,
      worldwide. AIM: The aim of this study was to screen the pregnant women for C.
      trachomatis and N. gonorrhoeae infections and to detect antimicrobial resistance
      pattern of N. gonorrhoeae. MATERIALS AND METHODS: This study was a prospective,
      hospital-based analysis of a random sample of pregnant women visiting the
      antenatal clinic of a tertiary hospital in eastern Saudi Arabia. Endocervical and
      high vaginal swabs were collected both from pregnant women and female patients
      attending gynecology clinic with lower genital tract infection (control group).
      C. trachomatis antigen was detected using enzyme-linked immunosorbent assay
      (ELISA). N. gonorrhoeae was detected by culture and identification of isolates,
      and antimicrobial susceptibility testing was performed. Statistical Package for
      Social Sciences (SPSS) version 13.0 and Chi-square test were used for statistical
      analysis. RESULTS: C. trachomatis antigen was detected in 10.5% (10/95) and 34.4%
      (35/102) of pregnant women and control group, respectively (P < 0.001). The
      isolation rate of N. gonorrhoeae among pregnant women was 0.0% compared to 7.8%
      (8/102) among the control group (P < 0.01). N. gonorrhoeae were resistant to
      penicillin (62.5%), tetracycline (50%), ampicillin (25%), amoxycillin-clavulinic
      acid (25%) and ciprofloxacin (37.5%), while they were susceptible to cefepime,
      ceftriaxone, ceftazidime, spectinomycin, and cefuroxime. CONCLUSION: Screening of
      pregnant women for C. trachomatis infection should be included in the antenatal
      care in this area. The detection rate of both organisms among the control group
      highlights the importance of preventive strategies. Certain antibiotics
      previously used in treating gonorrhea are no longer effective.

PMID- 21716787
TI  - Quality of life in HIV/AIDS.
AB  - Given the longevity achievable with current prophylactic and therapeutic
      strategies for persons with HIV infection, quality of life (QOL) has emerged as a
      significant medical outcome measure, and its enhancement has an important goal.
      This review highlights the relevance and complexity of physical, psychological,
      and social factors as determinants of health-related quality of life in HIV
      infected persons. Existing data suggest that physical manifestations,
      antiretroviral therapy, psychological well-being, social support systems, coping
      strategies, spiritual well-being, and psychiatric comorbidities are important
      predictors of QOL in this population. Consequently, the impact of HIV infection
      on the dimensions of QOL, including physical and emotional well-being, social
      support systems, and life roles, has emerged as a key issue for persons infected
      with HIV.

PMID- 21716788
TI  - Amoebic ulcer of the male genitala: A rare case report.
AB  - Amoebic ulcer of the penis is a very rare clinical entity. We report a case of
      amoebic ulcer of the glans penis in a 47-year-old male homosexual, symptomatic
      with severe pain and foul-smelling hemopurulent discharge of acute onset. He had
      received systemic antibiotics like ciprofloxacin and azithromycin prior to
      presentation with no improvement. Diagnosis was confirmed by wet mount
      microscopic examination of the discharge. The patient responded well to a course
      of metronidazole.

PMID- 21716789
TI  - Sexual health needs of people living with HIV in a rural area of central India.

PMID- 21716790
TI  - Extranodal non-Hodgkin's lymphoma of the gingiva in an HIV seropositive patient.
AB  - Among the myriad manifestations of HIV, non-Hodgkin's lymphomas (NHL) are
      considered as the second most common malignancies after Kaposi's sarcoma. HIV
      associated NHLs are extranodal and have a predilection for sites in the head and
      neck region in 50-60% of cases. Of all the extranodal NHLs, oral cavity
      constitutes only 25%. It is now considered that oral NHL serves as the first
      indicator of HIV infection.

PMID- 21716791
TI  - What is your diagnosis?

PMID- 21716792
TI  - Characterization of patients with multiple sexually transmitted infections: A
      hospital-based survey.
AB  - BACKGROUND: Many studies have examined the inter-relationship between different
      STI. There are, however, a few data on patients presenting with more than one
      concurrent sexually transmitted infection (STI). The aim of the study was to
      determine the burden of patients with more than one concurrent STI and to
      characterize factors associated with such infections. MATERIALS AND METHODS: Two
      hundred seventy five patients with one or more of the complaints, as enunciated
      by the World Health Organization (WHO) in its syndromic approach for the
      diagnosis of STI, were included as subjects. Detailed history, demographical
      data, and clinical features were recorded. All the patients were screened for
      common STIs. Multivariate analysis was performed taking all significant risk
      factor obtained from univariate analysis. RESULTS: A total of 102 (37%) patients
      were identified as having multiple STIs amongst whom 72% (73/102) were male, 70%
      were married, and except one none reported regular use of condom The age of first
      sexual exposure was 13-17 years, 31.3% had more than three sexual partners in the
      past 6 months, and 76.4% had contact with commercial sex workers (CSWs).
      Multivariate analysis revealed statistical significance in relation to marital
      status, number of sexual partners exposed in the past 6 months, age of first
      sexual exposure, and age of patient at the time of presentation. Syphilis (48%)
      was the most common infection associated with multiple STI followed by HIV (45%)
      and HSV-2 (39.2%). None of the patients with multiple infections were detected
      and managed accurately by syndromic approach. CONCLUSION: Pattern of concurrent
      multiple STIs and the clinical severity of such multiple infections may serve as
      an indicator of the type of host-pathogen interaction determining the outcome of
      infection. When patient had multiple STIs, syndromic approach was not axiomatic
      and thus underscores the need for laboratory diagnosis.

PMID- 21716793
TI  - Association between pelvic inflammatory disease and abortions.

PMID- 21716794
TI  - Immune reconstitution inflammatory syndrome in a unique clinical scenario.

PMID- 21716795
TI  - Plasma folate studies in HIV-positive patients at the Lagos university teaching
      hospital, Nigeria.
AB  - INTRODUCTION: In various studies globally, the prevalence of anemia in persons
      with HIV infection range from 10 to 20% at initial presentation, and anemia is
      diagnosed in 70 to 80% of these patients over the course of HIV disease. The
      etiology of anemia in this group of patients has not been fully established, thus
      a need to evaluate the role of plasma folate as a possible etiological factor.
      OBJECTIVE: This study was set to determine plasma folate levels in newly
      diagnosed, treatment naive, HIV-positive patients, and relate this to other
      hematological changes. MATERIALS AND METHODS: A total of 200 participants were
      recruited for this study, of which 100 were HIV positive, treatment naive
      patients who were recruited at the point of registration and 100 were HIV
      negative subjects (controls). 5 ml of venous blood was collected and plasma
      extracted for folic acid estimation by HPLC. A full blood count, CD4 and Viral
      load were estimated. RESULTS: Mean ages for control and study group were 38 +/-
      2.3 and 32 +/- 1.7 years, respectively. Mean plasma folate concentration among
      the study group (5.04 MUg/l) was significantly lower than that for the control
      group (15.89 MUg/l; P = 0.0002). Prevalence of anemia among the study group was
      72% (144 of 200), with a mean hemoglobin (Hb) concentration of 9.5 g/dl compared
      with mean Hb of 13.0 g/dl among the control group (P = 0.002). Plasma folate
      correlated positively with CD4 cell count (r = 0.304, P<0.05) and inversely with
      the viral load (r = -0.566; P<0.05). CONCLUSION: Plasma folate level is a
      predictor of anemia in early HIV infections.

PMID- 21716796
TI  - Pattern of sexually transmitted infections and performance of syndromic
      management against etiological diagnosis in patients attending the sexually
      transmitted infection clinic of a tertiary care hospital.
AB  - BACKGROUND AND OBJECTIVES: The availability of baseline information on the
      epidemiology of sexually transmitted infections (STIs) and other associated risk
      behaviors is essential for designing, implementing, and monitoring successful
      targeted interventions. Also, continuous analysis of risk assessment and
      prevalence-based screening studies are necessary to evaluate and monitor the
      performance of syndromic management. The aim of the present study was to document
      the pattern of common STIs and to evaluate the performance of syndromic case
      management against their laboratory diagnoses. MATERIALS AND METHODS: Three
      hundred consecutive patients who attended the STI clinic of a tertiary care
      hospital at Delhi, with one or more of the complaints as enunciated by WHO in its
      syndromic approach for the diagnosis of STIs, were included as subjects. Detailed
      history, demographical data, and clinical features were recorded and screened for
      common STIs by standard microbiological methods. RESULTS: The mean age was 24
      years and most of the male patients were promiscuous and had contact with
      commercial sex workers (CSWs 63.9%). Majority came with the complaint of genital
      discharge (63 males; 54 females) followed by genital ulcer (61 males; 30
      females). Genital herpes accounted for the maximum number of STI (86/300)
      followed by syphilis (71/300). The sensitivity of genital discharge syndrome
      (GDS) was high for Neisseria gonorrhoeae and Chlamydia trachomatis (96% and 91%,
      respectively) while specificity was low (76% and 72%, respectively). The
      sensitivity of genital ulcer syndrome for herpes simplex virus-2 (HSV-2) and
      Treponema pallidum was 82.65% and 81.2%, respectively, while specificity reached
      99% approximately. CONCLUSIONS: Viral STIs constitute the major burden of the STI
      clinic and enhance the susceptibility of an individual to acquire or transmit HIV
      through sexual contact. Syndromic algorithms have some shortcomings, and they
      need to be periodically reviewed and adapted to the epidemiological patterns of
      STI in a given setting.

PMID- 21716797
TI  - Luetic aortopathy: Revisited.
AB  - We report a case of 38-year-old male, who presented with a large pulsatile
      swelling on the left side of the anterior chest wall of 4 months' duration with a
      gradual increase in size. He gave history of sexual promiscuity in the form of
      unprotected sexual intercourse prior to his marriage in his early 20s. He also
      gave a history of ulceration on coronal sulcus of glans penis 20 years back with
      painless right inguinal mass. His blood serology was strongly positive for
      syphilis and hepatitis B surface antigen (HBsAg); however, serology for
      retroviral infection was negative. Computed tomography-angiography confirmed the
      pulsatile swelling as aneurysm of the arch of and ascending aorta. In view of the
      history, positive serology, and imaging studies, we concluded the aortic aneurysm
      to be of syphilitic origin. We report this case due to its extreme rarity in the
      present antibiotic era.

PMID- 21716798
TI  - Unusual cause of weight loss in a patient with HIV-hepatitis C virus coinfection.
AB  - Recombinant interferon alpha (IFN alpha), alone or in combination, is used
      extensively in the treatment of hepatitis C infection. IFN therapy is not free of
      side-effects and autoimmune thyroiditis is one of its rare side-effects. We
      present here a case of a patient with hepatitis C virus-human immunodeficiency
      virus coinfection on interferon therapy who presented with significant weight
      loss. He was found to have IFN-related autoimmune thyrotoxicosis and responded to
      antithyroid drugs and propanolol. Therefore, this case highlights that IFN
      induced thyroiditis is an unusual side-effect and that during treatment, a
      thyroid-stimulating hormone assay should be performed at regular intervals (every
      8-12 weeks).

PMID- 21716799
TI  - Seroprevalence of Hepatitis B and Hepatitis C virus infection among HIV infected
      patients in Mumbai.

PMID- 21716800
TI  - Prevention of parent to child transmission services and interventions - coverage
      and utilization: A cohort analysis in Gujarat, India.
AB  - BACKGROUND AND OBJECTIVES: Risk of vertical transmission (largest source of HIV
      in children) reduces from 33% to 3% with effective prevention of mother to child
      transmission (PMTCT) interventions. NACP-III has got an objective of testing all
      pregnant women for earliest linkage with PMTCT. Study was carried out to find out
      PPTCT service coverage, dropouts, intervention efficacy with other determinants.
      MATERIALS AND METHODS: At ICTCs, registered ANCs are counseled and tested for
      HIV. HIV +ve ANCs are additionally linked to services and followed-up for
      institutional delivery, sdNVP, nutrition and children testing. HIV +ve ANCs since
      2005 subsequently delivered till June 2008 and their exposed children in
      Gujarat's category A, B districts constituted study cohort. RESULTS: 259622
      pregnant women registered, 72.1% were counseled pre-test, 83.4% of them tested,
      74.4% received post-test counseling. 541 ANCs were detected HIV+ve. 45.5%
      delivered institutionally, 12.8% were unregistered. 12.1% were cesarian section
      and 66% delivered vaginally. 96.8% were live births, 92.13% mother-baby pair
      received sdNVP. 35% children could be traced till 18 months, 89% were alive. 90%
      were tested, 3 were found HIV +ve. Of them, none received MB Pair. Two were
      delivered vaginally, two received mixed feeding, two children's mothers were not
      linked with ART. CONCLUSIONS: PMTCT services - counseling and testing should be
      provided to all ANCs. EDD-based tracking, institutional deliveries, postnatal
      counseling to be encouraged along with complete MB pair coverage, capacity
      building of concerned staff regarding delivery of HIV+ve ANCs and exposed
      children tracking.

PMID- 21716801
TI  - Retromastoid-sub occipital: A novel approach to cerebello pontine angle in
      acoustic neuroma surgery-our experience in 21 cases.
AB  - BACKGROUND: Acoustic neuroma surgery poses significant challenges regarding
      definite management and preservation of hearing and the facial nerve are of great
      concern. AIM: To analyze the efficacy of the retromastoid approach in acoustic
      neuroma surgery. MATERIALS AND METHODS: Tumors operated between January 2002 and
      December 2008, by the authors, using the retromastoid approach, were analyzed.
      Twenty-one patients who presented with acoustic tumor were considered for this
      study. DISCUSSION: Precise knowledge of the neuroanatomy in the cerebellopontine
      angle is the key to success and microsurgical technique is the sole factor for
      good outcome. CONCLUSION: Retromastoid, in fact is the approach to the skull base
      with minimal or no damage to neurovascular structures, in contrast to the
      translabyrinthine or presigmoid approach.

PMID- 21716802
TI  - Effect of plant extracts on Alzheimer's disease: An insight into therapeutic
      avenues.
AB  - Alzheimer's disease (AD) is a devastative neurodegenerative disorder which needs
      adequate studies on effective treatment options. The extracts of plants and their
      effect on the amelioration of AD symptoms have been extensively studied. This
      paper summarizes the mechanisms like acetylcholinesterase (AChE) inhibition,
      modification of monoamines, antiamyloid aggregation effect, and antioxidant
      activity which are actively entailed in the process of amelioration of AD
      symptoms. These effects are induced by extracts of a few plants of different
      origin like Yizhi Jiannao, Moringa oleifera (Drumstick tree), Ginkgo Biloba
      (Ginkgo/Maidenhair tree), Cassia obtisufolia (Sicklepod), Desmodium gangeticum
      (Sal Leaved Desmodium), Melissa officinalis (Lemon Balm), and Salvia officinalis
      (Garden sage, common sage).

PMID- 21716803
TI  - Commentary.

PMID- 21716804
TI  - Placebo - More hatred than love.
AB  - A placebo is a sham medical intervention that can produce a placebo effect.
      Laboratory evidence supports the existence of several mechanisms of placebo
      effects in both healthy population and patients with a variety of medical
      conditions. The ethics of placebos have long been debated. However, accumulating
      ethical concern has arisen from the worldwide use of placebo in randomized
      control trials (RCTs), which may render their participants without early and
      optimal treatment. Although the pilgrimage of placebo is still on the way,
      refinement of controls in RCTs is worth paying new attention to.

PMID- 21716805
TI  - Computational ligand-based rational design: Role of conformational sampling and
      force fields in model development.
AB  - A significant number of drug discovery efforts are based on natural products or
      high throughput screens from which compounds showing potential therapeutic
      effects are identified without knowledge of the target molecule or its 3D
      structure. In such cases computational ligand-based drug design (LBDD) can
      accelerate the drug discovery processes. LBDD is a general approach to elucidate
      the relationship of a compound's structure and physicochemical attributes to its
      biological activity. The resulting structure-activity relationship (SAR) may then
      act as the basis for the prediction of compounds with improved biological
      attributes. LBDD methods range from pharmacophore models identifying essential
      features of ligands responsible for their activity, quantitative structure
      activity relationships (QSAR) yielding quantitative estimates of activities based
      on physiochemical properties, and to similarity searching, which explores
      compounds with similar properties as well as various combinations of the above. A
      number of recent LBDD approaches involve the use of multiple conformations of the
      ligands being studied. One of the basic components to generate multiple
      conformations in LBDD is molecular mechanics (MM), which apply an empirical
      energy function to relate conformation to energies and forces. The collection of
      conformations for ligands is then combined with functional data using methods
      ranging from regression analysis to neural networks, from which the SAR is
      determined. Accordingly, for effective application of LBDD for SAR determinations
      it is important that the compounds be accurately modelled such that the
      appropriate range of conformations accessible to the ligands is identified. Such
      accurate modelling is largely based on use of the appropriate empirical force
      field for the molecules being investigated and the approaches used to generate
      the conformations. The present chapter includes a brief overview of currently
      used SAR methods in LBDD followed by a more detailed presentation of issues and
      limitations associated with empirical energy functions and conformational
      sampling methods.

PMID- 21716806
TI  - The archaeological record speaks: bridging anthropology and linguistics.
AB  - This paper examines the origins of language, as treated within Evolutionary
      Anthropology, under the light offered by a biolinguistic approach. This
      perspective is presented first. Next we discuss how genetic, anatomical, and
      archaeological data, which are traditionally taken as evidence for the presence
      of language, are circumstantial as such from this perspective. We conclude by
      discussing ways in which to address these central issues, in an attempt to
      develop a collaborative approach to them.

PMID- 21716807
TI  - Systematic characterization of degas-driven flow for poly(dimethylsiloxane)
      microfluidic devices.
AB  - Degas-driven flow is a novel phenomenon used to propel fluids in
      poly(dimethylsiloxane) (PDMS)-based microfluidic devices without requiring any
      external power. This method takes advantage of the inherently high porosity and
      air solubility of PDMS by removing air molecules from the bulk PDMS before
      initiating the flow. The dynamics of degas-driven flow are dependent on the
      channel and device geometries and are highly sensitive to temporal parameters.
      These dependencies have not been fully characterized, hindering broad use of
      degas-driven flow as a microfluidic pumping mechanism. Here, we characterize, for
      the first time, the effect of various parameters on the dynamics of degas-driven
      flow, including channel geometry, PDMS thickness, PDMS exposure area, vacuum
      degassing time, and idle time at atmospheric pressure before loading. We
      investigate the effect of these parameters on flow velocity as well as channel
      fill time for the degas-driven flow process. Using our devices, we achieved
      reproducible flow with a standard deviation of less than 8% for flow velocity, as
      well as maximum flow rates of up to 3 nL/s and mean flow rates of approximately 1
      1.5 nL/s. Parameters such as channel surface area and PDMS chip exposure area
      were found to have negligible impact on degas-driven flow dynamics, whereas
      channel cross-sectional area, degas time, PDMS thickness, and idle time were
      found to have a larger impact. In addition, we develop a physical model that can
      predict mean flow velocities within 6% of experimental values and can be used as
      a tool for future design of PDMS-based microfluidic devices that utilize degas
      driven flow.

PMID- 21716808
TI  - Analysis of gene expression at the single-cell level using microdroplet-based
      microfluidic technology.
AB  - In the present work, we have measured the messenger RNA expression of specific
      genes both from total RNA and cells encapsulated in droplets. The microfluidic
      chip introduced includes the following functionalities: RNA/cell encapsulation,
      lysis, reverse transcription and real-time polymerase chain reaction. We have
      shown that simplex and duplex gene expression measurements can be carried out
      over a population of 100 purified RNA samples encapsulated simultaneously in 2 nl
      droplets in less than 2 h. An analysis of 100 samples containing one to three
      cells has shown excellent consistency with standard techniques regarding average
      values. The cell-to-cell distributions of the E-cadherin expression suggest
      fluctuations on the order of 80% in the number of transcripts, which is highly
      consistent with the general findings from the literature. A mathematical model
      has also been introduced to strengthen the interpretation of our results. The
      present work paves the way for the systematic acquisition of such information in
      biological and biomedical studies.

PMID- 21716809
TI  - Continuously perfused microbubble array for 3D tumor spheroid model.
AB  - Multi-cellular tumor spheroids (MCTSs) have been established as a 3D
      physiologically relevant tumor model for drug testing in cancer research.
      However, it is difficult to control the MCTS testing parameters and the entire
      process is time-consuming and expensive. To overcome these limitations, we
      developed a simple microfluidic system using polydimethylsiloxane (PDMS)
      microbubbles to culture tumor spheroids under physiological flow. The flow
      characteristics such as streamline directions, shear stress profile, and velocity
      profile inside the microfluidic system were first examined computationally using
      a COMSOL simulation. Colo205 tumor spheroids were created by a modified hanging
      drop method and maintained inside PDMS microbubble cavities in perfusion culture.
      Cell viability inside the microbubbles was examined by live cell staining and
      confocal imaging. E-selectin mediated cell sorting of Colo205 and MDA-MB-231 cell
      lines on functionalized microbubble and PDMS surfaces was achieved. Finally, to
      validate this microfluidic system for drug screening purposes, the toxicity of
      the anti-cancer drug, doxorubicin, on Colo205 cells in spheroids was tested and
      compared to cells in 2D culture. Colo205 spheroids cultured in flow showed a
      threefold increase in resistance to doxorubicin compared to Colo205 monolayer
      cells cultured under static conditions, consistent with the resistance observed
      previously in other MCTS models. The advantages presented by our microfluidic
      system, such as the ability to control the size uniformity of the spheroids and
      to perform real-time imaging on cells in the growth platform, show potential for
      high throughput drug screening development.

PMID- 21716810
TI  - Rosai-Dorfman disease presenting as a kidney tumour.
AB  - An 81-year-old Caucasian lady studied for anaemia presented with a large solid
      enhancing mass arising from the hilum of the left kidney on computed tomography
      scan. A laparoscopic left radical nephrectomy was done through a retroperitoneal
      approach. Microscopy and histochemistry classified it as Rosai-Dorfman disease
      though there was neither lymphadenopathy anywhere nor lymphocytosis. It was a
      very unusual urological presentation of a rare disease.

PMID- 21716811
TI  - An unusual complication of endoscopic retrograde cholangio-pancreatography
      (ERCP).

PMID- 21716812
TI  - Intracerebral haematoma without skull fracture by golf ball.
AB  - Serious head injury is very uncommon in golf and consists mostly of depressed
      skull fractures. A case of severe intracerebral haematoma without skull fracture
      caused by a stray golf ball is described and a review of head injuries in golf is
      provided.

PMID- 21716813
TI  - Serum creatine kinase elevation associated with olanzapine treatment.
AB  - On 2 May 2008, a 25-year-old male patient on olanzapine 15 mg developed mild
      central chest pain, and blood tests revealed a high creatine kinase (CK) value at
      1016 iu/l. Troponin, CK-MB, CK:MB ratio, full blood count (FBC), urea and
      electrolytes (U&E), C reactive protein (CRP) and glucose were all normal. Liver
      enzymes were marginally raised: alanine aminotransferase (ALT) 91 iu/l, gamma
      glutamyl transferase (GGT) 46 iu/l, alkaline phosphatase (ALP) 137 iu/l. The ECG
      was normal and the chest pain later resolved and was thought likely to be due to
      costochondritis. A repeat blood test on 7 May revealed further elevation of CK at
      1391 iu/l and olanzapine was stopped. CK continued to rise: 19 May 2857 iu/l, 20
      May 3285 iu/l, and 22 May 3646 iu/l. On 30 May CK dropped to 708 iu/l, on 20 June
      it was 593 iu/l, and on 30 June CK was 343 iu/l. The patient was started on
      amisulpiride on 15 July and CK began to rise again: on 18 July it was 445 iu/l
      and on 31 July CK was 480 iu/l, at which time the medication was stopped. The
      patient did not have any signs or symptoms of physical disorder on this
      occasion.We have never seen a patient develop such high CK values in the absence
      of any clinical or other significant laboratory abnormalities. We can rule out
      exercise as the cause as he attends an inpatient unit and we are aware that his
      exercise has been light to moderate at most; also, he stopped exercising at our
      request on 7 May 2008, yet CK continued to rise. There is no clinical indication
      of other causes of elevated CK such as myositis, and CK-MB and CK-MB:CK ratio
      were normal throughout, so it was not cardiac in origin. We believe olanzapine
      caused the elevated CK value. When the patient was rechallenged with amisulpiride
      on 15 May his CK again rose and the medication therefore had to be stopped. There
      are three similar cases that have been reported in the past when patients on
      second generation antipsychotics developed CK elevation in the absence of other
      clinical or laboratory abnormalities. We therefore believe this is an important
      finding to report.

PMID- 21716814
TI  - Autoimmune hepatitis following Epstein-Barr virus infection.
AB  - We describe a case of a young man with autoimmune hepatitis (AIH) following
      Epstein-Barr virus (EBV) infection, in whom a long follow-up showed favourable
      outcome with complete clinical recovery and failure to relapse after cessation of
      immunosuppressive therapy. The study underlines the importance of the
      differential diagnosis between primary EBV associated hepatitis with features of
      autoimmunity, in which there is a direct pathogenetic role of the virus, and EBV
      related AIH, in which EBV could act as the trigger of the immune mediated damage
      with probable differences between the two conditions with regard to the prognosis
      and the responsiveness to immunosuppressive treatment. The favourable outcome in
      our patient, better than most of the AIH cases, may be related both to the
      moderate necroinflammatory activity and to the low level of fibrosis at the
      beginning of the disease, or to the role of EBV as a trigger of AIH. The
      hypothesis that EBV related AIH could have a more favourable prognosis than most
      of the AIH cases in general needs to be confirmed in a larger series of studies.

PMID- 21716815
TI  - Valuable lessons from treatment of non-small cell lung cancer with erlotinib, an
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.

PMID- 21716816
TI  - Bilateral breast metastases of a renal carcinoma: a case report and review of the
      literature.
AB  - Metastatic tumours account for <1% of all breast malignancies, most originating
      in the contralateral breast. An 88-year-old woman presented with bilateral breast
      lumps 4 years after radical nephrectomy for a T2N0M0 renal cancer. Mammography
      showed a circumscribed 15 mm mass just below and medial to the left nipple
      without any micro-calcification. Ultrasound scan showed the presence of a solid
      vascular mass in the left breast; a guided core biopsy confirmed it as a
      metastatic renal cell carcinoma. Left simple mastectomy and excision of right
      breast lump was done. Histology of both lesions confirmed them as metastatic
      deposits. Bilateral breast metastasis from a renal cancer is very rare and this
      is the second reported case. This case illustrates the potential for rare sites
      of metastases and for the consideration of metastasis in the presence of previous
      renal cancer. Recognition as metastatic neoplasm is important to prevent
      unnecessary radical procedures.

PMID- 21716817
TI  - Thoracoscopy in diagnosis of ruptured pulmonary hydatid cyst.
AB  - A 26-year-old man presented with dyspnoea and pneumothorax diagnosed by chest
      radiography. He had previously presented with a massive right hydropneumothorax
      on his chest x ray 6 months ago, which was followed by 2 weeks of intercostal
      tube drainage resulting in a partial improvement of his symptoms. He was referred
      for a thoracoscopy to investigate the possible causes of the non-resolving
      pneumothorax, during which a large ruptured, crumpled hydatid cyst in the right
      pleural space, without empyema, was found. With a limited right thoracotomy, the
      crumpled laminated membrane of the hydatid cyst was removed. After extraction of
      the remaining particle of the laminated membrane of the same hydatid cyst in the
      right lower lobe and suturing of the bronchial opening, the pericyst layer was
      capitonnaged. Apart from common causes of pneumothorax in endemic areas, ruptured
      pulmonary hydatid cyst should be considered in pneumothoraces with an unusual
      clinical course.

PMID- 21716818
TI  - Spoon handle aspiration.

PMID- 21716819
TI  - Haemorrhagic transformation of a recent silent cerebral infarct during
      thrombolytic stroke treatment.
AB  - We present a patient in her 60s who was admitted with a sudden loss of power in
      her right arm and leg, right sided facial weakness, and difficulties with
      speaking. An acute ischaemic stroke in the left hemisphere was diagnosed and the
      patient received intravenous thrombolytic treatment. Treatment was stopped
      halfway as a cerebral haemorrhage was suspected. A small haemorrhage in the right
      frontal cortex was thereafter identified on computed tomography (CT) and magnetic
      resonance imaging scans. Re-examination of the CT scan taken before the start of
      thrombolytic treatment revealed a recent silent infarct with cortical petechial
      haemorrhage at this site. A month later the patient still suffered from a partial
      paralysis in her right arm and leg, but could now walk without help; she did not
      have any lasting symptoms of the haemorrhage. Our case illustrates that a recent
      silent infarct can be a cause of a haemorrhage at an unexpected site during
      thrombolytic treatment.

PMID- 21716820
TI  - Wegener's granulomatosis confined to nervous system.
AB  - Wegener's granulomatosis (WG) is a multisystemic necrotising granulomatous
      vasculitis of small and medium sized vessels, that primarily involves the upper
      and lower respiratory tracts, lung tissues and kidneys. Serum antineutrophil
      cytoplasmic antibodies (ANCA) are a sensitive and specific marker of WG. Whereas
      the peripheral nervous system is often involved in WG, central nervous system
      manifestations are reported only in 2-8%, and are rarely present at onset. We
      report on a patient with atypical neurological presentation of ANCA negative WG
      in whom the diagnosis was made only after a meningeal biopsy.

PMID- 21716821
TI  - Cluster headache or giant cell arteritis?
AB  - We describe an elderly female patient with known polymyositis who presented with
      new onset temporal headache that was diagnosed as giant cell arteritis but
      subsequently had a typical clinical course of cluster headache. This case
      illustrates the potential for diagnostic confusion between giant cell arteritis
      (GCA) and cluster headache (CH) and the need to consider CH as a potential
      differential diagnosis in those newly presenting with headaches, even in the
      elderly, and relapsing headaches in subjects with a diagnosis of GCA.
      Importantly, this needs to include female patients, a group historically thought
      to be much less likely to develop CH.

PMID- 21716822
TI  - A gibbus in puerperium.

PMID- 21716823
TI  - Atypical malignant round cell tumour of the femur.
AB  - We report an atypical case of malignant round cell tumour in a 25-year-old man
      who presented with pain in the left hip of insidious onset and long duration of
      about 11/2 years. Radiologically, the tumour was meta-epiphyseal in location with
      sparing of the diaphysis and showed a defined, narrow zone of transition. These
      appearances are contradictory to the well documented classical features of
      malignant round cell tumours, which usually present with a short history, are
      meta-diaphyseal in location, and appear ill-defined with a wide zone of
      transition due to infiltration of the adjacent bone.

PMID- 21716824
TI  - Perforation of a sigmoid diverticulum presenting with a pneumoscrotum and
      surgical emphysema.
AB  - A case of a sigmoid perforation presenting as a pneumoscrotum with progressive
      surgical emphysema is reported. An elderly patient presented with a grossly
      swollen scrotum and a distended abdomen. A computed tomography (CT) scan
      demonstrated sigmoid diverticulitis in conjunction with air and a
      subdiaphragmatic collection. A laparotomy was performed and revealed a perforated
      sigmoid diverticulum (Hinchey III). Sadly the patient died on the operating
      table. Intra-abdominal pathology manifesting as a pneumoscrotum and surgical
      emphysema is a rare yet reported phenomenon most often associated with
      colonoscopy, but also described with appendicitis and perforated colonic
      carcinoma. In previous reports, in contrast to this patient, the individual's
      scrotum was inflamed but not erythematous and tender, and the rapid progression
      of surgical emphysema is not reported.

PMID- 21716825
TI  - Fatal brain gas embolism during non-invasive positive pressure ventilation.
AB  - Gas embolism is a dreaded complication following invasive medical procedures,
      traumatic lung injury and decompression accidents. We report a case of fatal gas
      embolism following the use of non-invasive ventilation (NIV) with bilevel
      positive airway pressure (BiPAP). The patient initially underwent left bronchial
      artery embolisation for massive haemoptysis in the context of severe tuberculotic
      sequels. Under NIV and after heavy coughing he became hemiparetic and his level
      of consciousness suddenly dropped. Computed tomography of the brain showed
      multiple air embolism and ischaemic lesions were confirmed by magnetic resonance
      imaging. Echocardiographic investigations showed no intracardiac defect. Vasculo
      pulmonary abnormalities in the context of heavy coughing and non-invasive
      ventilation may have played a major role in the occurrence of this event. New
      neurological events in a patient with tuberculotic sequels or any known vascular
      pulmonary abnormalities and NIV should raise the suspicion of brain gas embolism.

PMID- 21716826
TI  - Gastrointestinal and urinary tract bleeding in methanol toxicity.
AB  - Methanol is a clear, colourless liquid with a smell and taste similar to ethanol.
      Intoxications with methanol are still frequent in large parts of the developing
      world. Haemodialysis should be done in cases of severe toxicity to eliminate
      toxic metabolites. In this case report, we describe a 37-year-old chronic alcohol
      abuser with methanol poisoning, who developed haematuria and upper
      gastrointestinal (GI) bleeding after haemodialysis. The upper GI endoscopic
      findings showed only low grade oesophageal ulceration. Haematuria and upper GI
      bleeding in our patient might also have cause by the effect of heparinisation
      during haemodialysis.

PMID- 21716827
TI  - Iatrogenic ulnar nerve injury resulting from a venous cut down procedure.
AB  - We present a case of an iatrogenic left ulnar nerve injury caused during the
      basilic vein cut down in a 25-year-old woman presenting with a ruptured ectopic
      pregnancy and requiring an emergency laparotomy. Two months after her discharge
      from the hospital, the patient presented to the hand surgery clinic with a weak
      grip strength and paraesthesias in the left hand, diagnosed to be resulting from
      a deficient ulnar nerve function. Surgical exploration of the nerve showed a
      complete section of the nerve. End to end repair and anterior transposition of
      the nerve was done. At 10 months follow up, the patient showed recovery in the
      flexor digitorum profundus and flexor carpi ulnaris, thus partially improving the
      grip strength. The patient was still under follow-up at the time this report was
      prepared.

PMID- 21716828
TI  - The effect of right or left handedness on caries experience and oral hygiene.
AB  - BACKGROUND: There is an indisputable relationship between tooth decay and oral
      hygiene. Caries can only be prevented by keeping tooth decay at bay. In several
      prophylactic methods, brushing is the most important. Brushing efficiency is
      directly related to an individuals' manual dexterity. OBJECTIVE: To investigate
      whether there were differences in oral hygiene and caries prevalence between
      right- and left-handers. MATERIALS AND METHODS: Forty-six elementary school
      students were included in the study. The subjects were 30 males and 16 females,
      ranging in age from 11 to 13 years. Handedness was ascertained by using the
      Edinburgh Handedness Scale. All students were examined intraorally. During this
      examination, the necessary values to determine oral hygiene status and to
      determine caries prevalence were recorded. RESULTS: It was observed that subjects
      who used their right hands were in a better position in terms of oral hygiene
      than those using the left (P < 0.01). In terms of caries prevalence, however,
      averages for right-handed individuals were lower than those for left-handed
      subjects, although the difference was not statistically significant. CONCLUSIONS:
      It can be stated that the right-handed individuals have better oral hygiene and
      the lower incidence of caries because of their better manual dexterity and brush
      efficiency. So, dentists should consider better manual dexterity and brush
      efficiency in right-handed individuals before treatment planning. However, future
      well-designed neurologic studies involving larger numbers of subjects will be
      necessary to confirm the findings of this study and to understand more about the
      effects of handedness on oral hygiene performance.

PMID- 21716829
TI  - Magnetic resonance "flip-flop" in idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension (IIH) is a headache syndrome with raised CSF
      pressure in the absence of an intracranial mass lesion. Though earlier confined
      to excluding intracranial lesions, magnetic resonance imaging (MRI) in recent
      years has been shown to identify intracranial changes from prolonged raised CSF
      pressure, suggestive of IIH. We present the MRI and TOF (time-of-flight)
      venography findings involving the orbit, sella tursica and cerebral venous
      structures in a 45-year-old lady with IIH and illustrate their reversibility
      ("flip-flop") following CSF drainage. Our case highlights the role of imaging in
      evaluation and follow-up of patients with IIH, without the need for repeated
      lumbar punctures to monitor pressures.

PMID- 21716830
TI  - A case of a massive mandibular schwannoma.
AB  - Schwannoma, a benign nerve sheath tumor is relatively rare in occurrence and even
      rarer in sites, such as jaw bones. There are only 45 reported cases of
      intraosseous schwannoma of the jaws reported in the literature. We report a rare
      case of mandibular schwannoma in a 50-year-old Indian male. The clinical features
      resembled that of a residual cyst, fibro-osseous lesion or an odontogenic
      tumor/cyst. Radiological differential diagnoses of ameloblastoma or odontogenic
      keratocyst was made based on the findings of the orthopantomogram. The lesion was
      examined histopathologically and a final diagnosis of schwannoma arising from the
      inferior alveolar nerve was made. The aim of this report is to add information to
      the existing sparse literature on intraosseous schwannomas of the jaw.

PMID- 21716831
TI  - Depression in elderly patients with Alzheimer dementia or vascular dementia and
      its influence on their quality of life.
AB  - BACKGROUND: Alzheimer dementia (AD) and vascular dementia (VD) are the most
      common causes of dementia in the elderly. Depression is an important co-morbid
      disorder in these diseases, which is often challenging to recognize. We
      investigated the prevalence of depression in patients with AD and VD and
      estimated the influence of depression on the health-related quality of life
      (HrQoL) in these patients. MATERIALS AND METHODS: We evaluated prevalence of
      depression in consecutively recruited patients with AD or VD (n= 98). Depression
      was diagnosed according to criteria of the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV) and scored using the Geriatric Depression Scale. The
      EuroQol (EQ-5D and visual analogue scale) was applied to evaluate HrQoL. The
      severity of cognitive impairment was measured by the Mini-Mental State
      Examination (MMSE). Multiple regression analysis was used to identify factors
      predicting severity of depression. RESULTS: The prevalence of depression in AD/VD
      was 87%. In comparison to the general population, HrQoL measured on the visual
      analogue scale was reduced by 54% in patients with AD/VD. In the dimension
      "anxiety/depression" of the EQ-5D, 81% of patients with AD/VD had moderate or
      severe problems. Depression showed significant association with reduced HrQoL
      (P<0.01). Independent predictors of more severe depression were older age, male
      gender, better MMSE scores and being not married. CONCLUSIONS: Depression is a
      prevalent psychiatric co-morbidity in patients with AD/VD, which is often under
      diagnosed being masked by cognitive impairment. Depression is a predictor of
      reduced HrQoL in elder people with AD/VD. Therefore, they should be screened for
      presence of depressive symptoms and receive adequate antidepressant treatment.

PMID- 21716832
TI  - Watering flowers in the rain: The elusive nature of executive dysfunction in HIV.
AB  - Individuals infected with human immunodeficiency virus (HIV) frequently
      experience both neurocognitive and psychiatric dysfunction. Apathy is a prominent
      neuropsychiatric symptom associated with HIV and is related to neurologic
      dysfunction. In contrast, depression is independent of neurocognitive impairment
      in HIV. This case report illustrates the importance of behavioral observations
      from family members of HIV-positive (HIV+) individuals as a valuable source of
      information. These behavioral observations can be particularly important in rural
      resource-limited settings, where cognitive testing is often limited to
      standardized mental status examinations.

PMID- 21716833
TI  - Headache in a 27-year-old man: Bilateral serous retinal detachment.
AB  - A 27-year-old man with a complaint of headache, tinnitus, and visual obscuration
      presented to a neurologist. Neurologic evaluations, including MRI and CT scan,
      were within normal limit. The prescribed medicines were propranolol, sumatriptin,
      valproate sodium, and dexamethasone. Ophthalmic examination was associated with
      reduction of visual acuity of eyes, bilateral uveitis, and serous retinal
      detachment. The most probable diagnosis was Vogt-Koyanagi-Harada (VKH) disease.
      Prescribing high-dose oral steroid and acetazolamide-improved systemic and ocular
      symptoms. Although HLAB(5) is positive in Behetaet disease, it also may be seen
      in VKH.

PMID- 21716834
TI  - Musculocutaneous nerve substituting for the distal part of radial nerve: A case
      report and its embryological basis.
AB  - In the present case, we have reported a unilateral variation of the radial and
      musculocutaneous nerves on the left side in a 64-year-old male cadaver. The
      radial nerve supplied all the heads of the triceps brachii muscle and gave
      cutaneous branches such as lower lateral cutaneous nerve of the arm and posterior
      cutaneous nerve of forearm. The radial nerve ended without continuing further.
      The musculocutaneous nerve supplied the brachioradialis, extensor carpi radialis
      longus and extensor carpi radialis brevis muscles. The musculocutaneous nerve
      divided terminally into two branches, superficial and deep. The deep branch of
      musculocutaneous nerve corresponded to usual deep branch of the radial nerve
      while the superficial branch of musculocutaneous nerve corresponded to usual
      superficial branch of the radial nerve. The dissection was continued to expose
      the entire brachial plexus from its origin and it was found to be normal. The
      structures on the right upper limb were found to be normal. Surgeons should keep
      such variations in mind while performing the surgeries of the upper limb.

PMID- 21716835
TI  - Changing scenario of neuropractice.

PMID- 21716836
TI  - Delayed presentation of spinal cord trauma.

PMID- 21716837
TI  - Painful tic convulsif syndrome due to vertebrobasilar dolichoectasia.
AB  - Combined clinical presentation of hemifacial spasm and ipsilateral trigeminal
      neuralgia is also known as painful tic convulsif (PTC). It is a rare condition
      and the most common cause is vascular compression. Vertebrobasilar dolichoectasia
      (VBD) is characterized by dilated and tortuous vertebral and basilar arteries.
      VBD is an uncommon and rarely reported cause of PTC. Magnetic resonance imaging
      (MRI), due to its inherent excellent contrast resolution, is an excellent
      modality for demonstrating the nerve compression by dilated and tortuous vessels
      seen in this condition. For this purpose, 3D MRI sequences are especially useful
      like constructive interference in steady state (CISS) and MR angiography. Both of
      these have been reported to be helpful in the diagnosis of this condition. We
      report a case of PTC in which we were able to document facial and trigeminal
      nerve compression by VBD on MRI, using CISS and time-of-flight MR angiography.

PMID- 21716838
TI  - Rehabilitation for cerebral palsy: Analysis of the Australian rehabilitation
      outcome dataset.
AB  - OBJECTIVE: To examine the outcome of inpatient rehabilitation for cerebral palsy
      (CP), using the Australian Rehabilitation Outcomes Center (AROC) database.
      MATERIALS AND METHODS: De-identified data from the AROC database was analyzed for
      all rehabilitation admissions during 2003 - 2008, using four classes for the
      functional level. The outcomes included: Functional Independence Measure (FIM)
      scores, FIM efficiency, hospital length of stay (LOS), and discharge destination.
      RESULTS: Of 141 case episodes 56.7% were female, mean age 48.5 years, 87.2% were
      discharged to the community and 64.5% (n = 91) were in the lowest functional
      classes (217, 218, and 219). The majority of CP patients were treated in the
      public hospital system (66.7% versus 33.3%), and had a slightly longer LOS
      compared with those treated in private facilities (22.6 versus 17.9 days, mean
      difference - 4.7 days, 95% CI - 9.2 to - 0.2, P = 0.041). The FIM for all classes
      (216 - 218) showed significant functional improvement during the admission (P =
      0.001). As expected those in the most functionally impaired classes showed most
      change (FIM change: 16.6 in class 217, 15.3 in class 218). FIM efficiency was the
      highest in classes 217 compared to the other classes. The year-to-year trend
      demonstrated a mixed pattern for hospital LOS and was not significant (P =
      0.492). CONCLUSION: The AROC dataset is a valuable research tool for describing
      rehabilitation outcomes. However, more specific information needs to be collected
      alongside the core AROC data, to allow a more meaningful evaluation of outcomes
      for CP rehabilitation.

PMID- 21716839
TI  - Commentary.

PMID- 21716840
TI  - Commentary.

PMID- 21716841
TI  - Horizontal canal benign paroxysmal positional vertigo in a fighter pilot.
AB  - Benign paroxysmal positional vertigo (BPPV) is the most common disorder of the
      peripheral vestibular system, characterized by intense, positional provoked
      vertigo. BPPV is thought to occur due to canalithiasis of the posterior
      semicircular canal. Recently, a new entity of BPPV, known as horizontal canal
      (HC)-BPPV, has been recognized. Although only 3 to 8% of BPPV is due to
      horizontal canal involvement, HC-BPPV is not rare. We present a case of a naval
      fighter pilot who had an incident of HC-BPPV on the ground. The pilot aeromedical
      evaluation and considerations are discussed.

PMID- 21716842
TI  - Tuberculous lumbar arachnoiditis mimicking conus cauda tumor: A case report and
      review of literature.
AB  - Tuberculous spinal arachnoiditis involving cauda equina is rare. A patient with
      lumbar tuberculous arachnoiditis in the absence of both vertebral and meningeal
      tuberculosis, which was mimicking spinal intradural extramedullary tumor is
      described here. Diagnosis was made based on intraoperative findings and was
      confirmed by histopathology. Surgical decompression along with a combination of
      steroid and antitubercular therapy resulted in a good outcome. At 3 months follow
      up, the patient regained bladder control and was able to walk with support.
      Clinical features, magnetic resonance imaging, and intraoperative findings are
      described. Pathology and the relevant literature are discussed. Based on the
      patient's clinical and radiologic findings, it was believed that the patient had
      a conus cauda tumor and was operated on. Histologic examination of the mass
      revealed tuberculoma. Surgical decompression followed by antituberculosis
      medication resulted in good outcome. Hence tuberculous arachnoiditis should be
      considered in differential diagnosis of conus cauda tumors.

PMID- 21716843
TI  - Objective assessment of utility of intraoperative ultrasound in resection of
      central nervous system tumors: A cost-effective tool for intraoperative
      navigation in neurosurgery.
AB  - BACKGROUND: Localization and delineation of extent of lesions is critical for
      safe maximal resection of brain and spinal cord tumors. Frame-based and frameless
      stereotaxy and intraoperative MRI are costly and not freely available especially
      in economically constrained nations. Intraoperative ultrasound has been around
      for a while but has been relegated to the background. Lack of objective evidence
      for its usefulness and the perceived "user unfriendliness" of US are probably
      responsible for this. We recount our experience with this "forgotten" tool and
      propose an objective assessment score of its utility in an attempt to revive this
      practice. MATERIALS AND METHODS: Seventy seven intraoperative ultrasound (IOUS)
      studies were carried out in patients with brain and spinal cord tumors. Seven
      parameters were identified to measure the "utility" of the IOUS and a "utility
      score" was devised (minimum 0 and maximum 7). Individual parameter and overall
      scores were calculated for each case. RESULTS: IOUS was found to be useful in
      many ways. The median overall score was 6 (mean score 5.65). There were no scores
      less than 4 with the majority demonstrating usefulness in 5 or more parameters
      (91%). The use of the IOUS significantly influenced the performance of the
      surgery in these cases without significantly prolonging surgery. CONCLUSIONS: The
      IOUS is a very useful tool in intraoperative localization and delineation of
      lesions and planning various stages of tumor resection. It is easy, convenient,
      reliable, widely available, and above all a cost-effective tool. It should be
      increasingly used by neurosurgeons in the developing world where costlier
      intraoperative localization and imaging is not available freely.

PMID- 21716844
TI  - Dolichoectasia of vertebrobasilar arteries as a cause of hydrocephalus.
AB  - Dolichoectasia of vertebrobasilar artery is a condition in which the
      vertebral/basilar artery is elongated, distended and tortuous. It is usually
      asymptomatic. It may present with compressive or ischemic symptoms. Hydrocephalus
      as a complication of vertebrobasilar dolichoectasia is rare. We present a case of
      a 60-year-old male with dolichoectasia of the basilar artery causing compression
      of the third ventricular outflow and, thus, presenting with noncommunicating
      hydrocephalus.

PMID- 21716845
TI  - Quality of life in patients with epilepsy in India.
AB  - BACKGROUND: People with epilepsy have impairment in their quality of life (QOL)
      due to effect of epilepsy on various aspects of their life and the medication
      effects. Systematic studies on QOL in epilepsy from developing countries are
      sparse. OBJECTIVES: To assess the QOL in people with epilepsy and to evaluate
      various factors affecting the QOL in them. MATERIALS AND METHODS: People with
      generalized and partial epilepsy on medication aged more than 18 years were
      included in the study. The QOL was assessed with QOLIE-89 instrument. Statistical
      significance was evaluated by the use of Chi-square test and one-way analysis of
      variance (ANOVA). RESULTS: Sixty people with epilepsy were studied among whom the
      older patients had lower overall QOL scores compared to younger patients. Female
      patients had lower scores compared to males. Married people had lower quality of
      health score. Patients with simple partial seizures had lowest overall QOL mean
      score. There was reduction in the overall QOLIE scores with increasing duration
      of the epilepsy. Patients who had their last seizure within 10 months prior to
      evaluation had lower mean overall scores. CONCLUSION: QOL was impaired in people
      with epilepsy with increased impairment in women, older patients, simple partial
      seizures, and those with recent seizure.

PMID- 21716846
TI  - 4th Edition of the International Autologous and Allogeneic Cell Therapy for Solid
      Tumors (ATST) Meeting.
AB  - The fourth edition of the International Autologous and Allogeneic Cell Therapy
      for Solid Tumors (ATST) meeting was held in Venice, Italy, between March 31 and
      April 1, 2011.

PMID- 21716847
TI  - Novel monoclonal antibodies for cancer treatment: the trifunctional antibody
      catumaxomab (removab).
AB  - THE TRIFUNCTIONAL ANTIBODY (TRAB) CATUMAXOMAB IS CHARACTERIZED BY A UNIQUE
      ABILITY TO BIND THREE DIFFERENT CELL TYPES: tumor cells; T-cells; and accessory
      cells. It binds to epithelial cell adhesion molecule (EpCAM) on tumor cells, the
      CD3 antigen on T-cells, and to type I, IIa, and III Fcgamma receptors (FcgammaRs)
      on accessory cells (e.g. natural killer cells, dendritic cells, and macrophages).
      Catumaxomab exerts its anti-tumor effects via T-cell-mediated lysis, antibody
      dependent, cell-mediated cytotoxicity, and phagocytosis via activation of
      FcgammaR-positive accessory cells. Catumaxomab represents a self-supporting
      system, as no additional immune cell activation is required for tumor
      eradication. The efficacy and safety of catumaxomab have been demonstrated in a
      pivotal phase II/III study in malignant ascites (MA) and supporting phase I/II
      studies. It is administered as four intraperitoneal (i.p.) infusions of 10, 20,
      50, and 150 ug on days 0, 3, 7, and 10, respectively. Catumaxomab was approved
      for the i.p. treatment of MA in patients with EpCAM-positive carcinomas where
      standard therapy is not available or no longer feasible in the European Union in
      April 2009. It is the first trAb and the first drug in the world approved
      specifically for the treatment of MA. Catumaxomab was awarded the Galen of
      Pergamon Prize, which recognizes pharmacological research for developing new and
      innovative drugs and diagnostics, in the specialist care category in 2010. The
      use of catumaxomab in other indications and additional routes of administration
      are currently being investigated to further exploit its therapeutic potential in
      EpCAM-positive carcinomas.

PMID- 21716848
TI  - Immune effects of trastuzumab.
AB  - Trastuzumab's targeted therapy has become a stronghold for human epidermal growth
      factor receptor 2 positive breast cancer patients. This humanized monoclonal
      antibody binds to the extracellular juxta-membrane domain of HER2 and inhibits
      the proliferation and survival of HER2 dependent cancer cells. The ways by which
      this molecule exerts its action have been partially elucidated but several new
      mechanisms are being constantly identified. Several new agents are being
      introduced that interfere with HER2. Several new immunotherapy strategies are
      being introduced in order to direct the immune system against cells and tissues
      that aberrantly overexpressed HER2. We review the strategies currently adopted
      and those suggested against HER2 expressing tumors.

PMID- 21716849
TI  - Targeting EGFR in Triple Negative Breast Cancer.
AB  - Our preliminary data show that erlotinib inhibits Triple-negative breast cancer
      (TNBC) in a xenograft model. However, inhibition of metastasis by erlotinib is
      accompanied by nonspecific effects because erlotinib can inhibit other kinases;
      thus, more direct targets that regulate TNBC metastasis need to be identified to
      improve its therapeutic efficacy.

PMID- 21716850
TI  - A Clinical Study of a Cell-Based MAGE-A3 Active Immunotherapy in Advanced
      Melanoma Patients.
AB  - In this bi-institutional study, twenty-three stage IIIC-IV MAGE-A3(+) melanoma
      patients were vaccinated with M3TK-GML biweekly at three dose levels, with a
      subsequent phase of vaccinations at the maximum dose level. Anti-MAGE-A3 and anti
      TK T cells were assessed by in vitro assay and delayed-type hypersensitivity skin
      testing.

PMID- 21716851
TI  - Chimeric Antigen Receptor Therapy for B-cell Malignancies.
AB  - We presented data showing that the CART-19 cells expressing the 4-1BB signaling
      domain can have unprecedented and massive in-vivo expansion, traffic to tumor
      sites, persist long term in vivo, and induce rapid and potent anti-tumor activity
      in chemotherapy refractory CLL patients.

PMID- 21716852
TI  - Immunological effects of multikinase inhibitors for kidney cancer: a clue for
      integration with cellular therapies?
AB  - The multikinase inhibitors Sunitinib and Sorafenib not only inhibit angiogenesis
      and tumor growth, but also have the potential of interacting with the function of
      the immune system.Presently available data seem to suggest that Sorafenib may
      exert immune suppressive effects, whilst the effects of Sunitinib are not so
      clear, being immune stimulatory in the vast majority - but not all - the studies
      reported.Trials of combination of these multikinase inhibitors with different
      types of immune manipulation - and cellular therapies in particular - should be
      rationally designed taking into account all these complex effects, which
      ultimately deserve further insights.

PMID- 21716853
TI  - Innovative platforms for haploidentical stem cell transplantation: the role of
      unmanipulated donor graft.
AB  - We exploited the dual positive effects of rapamycin to prevent GvHD and control
      malignant cells upon infusion of unmanipulated grafts from family haploidentical
      donors to patients affected by advanced hematological malignancies. Preliminary
      results on 45 patients show the feasibility of this platform with an appreciable
      low rate of GvHD.

PMID- 21716854
TI  - T cell therapy for nasopharyngeal carcinoma.
AB  - Among the novel biologic therapeutics that will increase our ability to cure
      human cancer in the years to come, T cell therapy is one of the most promising
      approaches. However, with the possible exception of tumor-infiltrating
      lymphocytes therapy for melanoma, clinical trials of adoptive T-cell therapy for
      solid tumors have so far provided only clear proofs-of-principle to build on with
      further development. Epstein-Barr virus (EBV)-associated malignancies offer a
      unique model to develop T cell-based immune therapies, targeting viral antigens
      expressed on tumor cells. In the last two decades, EBV-specific cytotoxic T
      lymphocytes (CTL) have been successfully employed for the prophylaxis and
      treatment of EBV-related lymphoproliferative disorders in immunocompromised
      hosts. More recently, this therapeutic approach has been applied to the setting
      of EBV-related solid tumors, such as nasopharyngeal carcinoma. The results are
      encouraging, although further improvements to the clinical protocols are clearly
      necessary to increase anti-tumor activity. Promising implementations are
      underway, including harnessing the therapeutic potential of CTLs specific for
      subdominant EBV latent cycle epitopes, and delineating strategies aimed at
      targeting immune evasion mechanisms exerted by tumor cells.

PMID- 21716855
TI  - Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Cancer (RCC).
AB  - A variety of therapeutic options are now available for advanced renal cell
      cancer, including antiangiogenic and anti-mTOR agents. Allogeneic hematopoietic
      stem cell transplantation, through its graft-versus-tumor effect, can induce
      clinical responses and prolonged survival in selected cytokine-refractory
      patients. However, the still relevant transplant-related mortality due to
      toxicity and graft-versus-host disease is an obstacle to its widespread use.

PMID- 21716856
TI  - Immunotherapeutic Intervention against Sarcomas.
AB  - Advances in systemic therapy for sarcoma have produced, over the last two
      decades, relatively short-term benefits for the majority of patient. Among the
      novel biologic therapeutics that will likely increase our ability to cure human
      cancer in the years to come, immunotherapy is one of the most promising
      approaches. While past attempts to use immunotherapy have failed to dramatically
      shift the paradigm of care for the treatment of patients with sarcoma, major
      advances in basic and translational research have resulted, in more recent years,
      in clinical trial activity that is now beginning to generate promising results.
      However, to move from "proof of principle" to large scale clinical applicability,
      we need well-designed, multi-institutional clinical trials, along with continuous
      laboratory research to explore further the immunological characteristics of
      individual sarcoma subtypes and the consequent tailoring of therapy.

PMID- 21716857
TI  - The adaptive radiation of cichlid fish in lake tanganyika: a morphological
      perspective.
AB  - Lake Tanganyika is the oldest of the Great Ancient Lakes in the East Africa. This
      lake harbours about 250 species of cichlid fish, which are highly diverse in
      terms of morphology, behaviour, and ecology. Lake Tanganyika's cichlid diversity
      has evolved through explosive speciation and is treated as a textbook example of
      adaptive radiation, the rapid differentiation of a single ancestor into an array
      of species that differ in traits used to exploit their environments and
      resources. To elucidate the processes and mechanisms underlying the rapid
      speciation and adaptive radiation of Lake Tanganyika's cichlid species assemblage
      it is important to integrate evidence from several lines of research. Great
      efforts have been, are, and certainly will be taken to solve the mystery of how
      so many cichlid species evolved in so little time. In the present review, we
      summarize morphological studies that relate to the adaptive radiation of Lake
      Tanganyika's cichlids and highlight their importance for understanding the
      process of adaptive radiation.

PMID- 21716858
TI  - Low genetic and morphometric intraspecific divergence in peripheral copadichromis
      populations (perciformes: cichlidae) in the lake Malawi basin.
AB  - Peripheral isolated populations may undergo rapid divergence from the main
      population due to various factors such as a bottleneck or a founder effect
      followed by genetic drift or local selection pressures. Recent populations of two
      economically important Copadichromis species in Lake Malombe, a satellite lake of
      Lake Malawi, were neither genetically nor morphometrically distinct from their
      source populations in the main lake. Evidence was found for a founder effect
      which had a different impact on the genetic composition of the two species. In
      addition, the increased fishing pressure in Lake Malombe may have led to a
      reduction of the body sizes of both species.

PMID- 21716859
TI  - Post-salpingectomy endometriosis: An under-recognized entity.
AB  - We report a case of a 48-year old lady, who presented with complaints of lower
      abdominal pain and menorrhagia for the last four months. The patient had
      undergone bilateral salpingectomy four years back by the Pomeroy technique.
      Ultrasonography revealed an ovarian cyst on the right side. A total abdominal
      hysterectomy with bilateral salpingo-oophorectomy was performed and the specimen
      was sent for histopathological examination. It revealed that the normal mucosa of
      the tubectomy stump was completely replaced by endometrial tissue. Tubal
      endometriosis remains an under-recognized entity, due to less extensive routine
      sampling of the fallopian tubes, and they may be also be associated with other
      pathologies, as was in the present case.

PMID- 21716860
TI  - Socio-demographic Factors of Geriatric Depression.
AB  - BACKGROUND: Depression is a common mental health problem in geriatric population
      and the overall prevalence rate of depression in this age group varies between 10
      and 20%. OBJECTIVE: To study the socio-demographic factors associated with
      depression in geriatric population. MATERIALS AND METHODS: A systematic review
      was done on 74 community-based mental health surveys on depression in geriatric
      population, which were conducted in the continents of Asia, Europe, Australia,
      North America, and South America. All the studies were conducted between 1955 and
      2005. The researchers had included only community-based cross-sectional surveys
      and some prospective studies that had not excluded depression on baseline. These
      studies were conducted on homogenous community of geriatric population in the
      world, who were selected by simple random sampling technique. A qualitative
      analysis was conducted to study the socio-demographic factors of depression.
      RESULTS AND CONCLUSION: The two non-modifiable risk factors found to be
      significantly associated with depression in geriatric population were "older age
      group" and "female gender". However, the potentially modifiable risk factors for
      depression in the geriatric population were identified as low socioeconomic
      status, loss of spouse, living alone, chronic co-morbidities, cognitive
      impairment, bereavement and restricted activities of daily living (ADL).

PMID- 21716862
TI  - Suicide incidence and epidemiology.

PMID- 21716861
TI  - Ethics for medical educators: an overview and fallacies.
AB  - Ethics is the rule of right conduct or practice in a profession. The basic
      principles of ethics are beneficence, justice and autonomy or individual freedom.
      There is very minor demarcation between ethics and the law. The ethics is
      promulgated by the professional bodies. All are expected to guide the medical
      professional in their practice. Medical educators have dual ethical obligations:
      firstly, to the society at large which expects us to produce competent health
      professionals, and secondly, to the students under our care. The students observe
      and copy what their teacher does and his/her role modelling can be a gateway to a
      student's character building. Due to rapid increase in the number of medical
      colleges, privatization, and capitalism, ethical issue has become much more
      relevant and needs to discuss in detail. The present paper discusses the ethics
      for medical educators in detail with, basic principles, common breaches of ethics
      and fallacies due to wrong application of ethical principles, and the approach to
      ethics and methods by which we can prevent and avoid breach of ethics.

PMID- 21716863
TI  - Childhood depression with unremitting suicidal behavior.
AB  - The diagnostic criteria for major depressive disorder in adults can be applied to
      children and adolescents, as well, but the predominance and characteristics of
      symptoms in children varies widely than in adults.

PMID- 21716864
TI  - Eye movement desensitization and reprocessing: a conceptual framework.
AB  - Eye movement desensitization and reprocessing (EMDR) is a method which was
      initially used for the treatment of post-traumatic stress disorder. But it is now
      being used in different therapeutic situations. EMDR is an eight-phase treatment
      method. History taking, client preparation, assessment, desensitization,
      installation, body scan, closure and reevaluation of treatment effect are the
      eight phases of this treatment which are briefly described. A case report is also
      depicted which indicates the efficacy of EMDR. The areas where EMDR is used and
      the possible ways through which it is working are also described.

PMID- 21716865
TI  - A structured approach to brain injury rehabilitation.

PMID- 21716866
TI  - Single photon emission computed tomography scanning: A predictor of outcome in
      vegetative state of head injury.
AB  - BACKGROUND: Neurotrauma is one of the most important causes of death and
      disability. Some of the severely head injured patients, failed to show
      significant improvement despite aggressive neurosurgical management and ended up
      in a vegetative state. AIMS: To assess the outcome at six months and one year
      using Glasgow outcome scale (GOS), in this prospective study on patients with
      severe head injury, who remained vegetative at one month. MATERIALS AND METHODS:
      This prospective study was carried out in the department of Neurosurgery, All
      India Institute of Medical Sciences (AIIMS), New Delhi, over a period of a year
      and a half (March 2002 through July 2003). MATERIALS AND METHODS: In patients
      with severe head injury (GCS < 8), post resuscitation, neurological assessment
      was done with Glasgow coma scale (GCS), pupillary light reflex, doll's eye
      movement and cold caloric test in all cases. Fifty patients, who remained
      vegetative post injury according to the criteria of Jennett and Plum, at one
      month, were considered for the study. Brain SPECT (Single Photon Emission
      Computed T omography) Scanning was carried out in selected cases. STATISTICAL
      ANALYSIS: Data analysis was done by Pearson's chi-square test on computer
      software SPSS, Version 10 (California, USA). RESULTS: Patients with preserved
      brainstem reflex and with no perfusion defect on SPECT scan had statistically
      significant favorable outcome. More than 40% of vegetative patients regained
      consciousness by the end of one year, of whom 24% had favorable outcome in the
      form of moderate disability and good recovery. CONCLUSION: SPECT is better than
      computed tomography/magnetic resonance imaging (CT/MRI) as it assesses the
      cerebral perfusion and functional injury rather than detecting the lesions only.
      Further study with a control group is necessary to establish the role of SPECT in
      head injury.

PMID- 21716867
TI  - Sporadic cerebral amyloid angiopathy: An important cause of cerebral hemorrhage
      in the elderly.
AB  - Cerebral amyloid angiopathy (CAA) is an important cause of primary intracerebral
      hemorrhage (PICH) in the elderly. Although there are no pathognomic clinical
      features of CAA-related PICH, the association of white matter changes with lobar,
      recurrent, or multiple simultaneous hemorrhages in older patients should raise
      the suspicion of its diagnosis. A definitive diagnosis of CAA requires pathologic
      examination of the affected tissue. However, with modern imaging techniques, it
      is possible to diagnose the "probable CAA" in patients presenting with PICH.
      Gradient-echo magnetic resonance imaging is a very sensitive, noninvasive
      technique for identifying microhemorrhages in life. The diagnosis of CAA is
      important because of the likely implication it has on future management targeted
      to reduce risk of future bleeding.

PMID- 21716868
TI  - Marcus Gunn phenomenon with abducens palsy: As pseudo-false localizing signs.

PMID- 21716869
TI  - Spinal shortening and monosegmental posterior spondylodesis in the management of
      dorsal and lumbar unstable injuries.
AB  - INTRODUCTION: Patients with spinal injuries have been treated in the past by
      laminectomy in an attempt to decompress the spinal cord. The results have shown
      insignificant improvement or even a worsening of neurologic function and
      decreased stability without effectively removing the anterior bone and disc
      fragments compressing the spinal cord. The primary indication for anterior
      decompression and grafting is narrowing of the spinal canal with neurologic
      deficits that cannot be resolved by any other approach. One must think of
      subsequent surgical intervention for increased stability and compressive
      posterior fusion with short-armed internal fixators. AIM: To analyze the results
      and efficacy of spinal shortening combined with interbody fusion technique for
      the management of dorsal and lumbar unstable injuries. MATERIALS AND METHODS:
      Twenty-three patients with traumatic fractures and or fracture-dislocation of
      dorsolumbar spine with neurologic deficit are presented. All had radiologic
      evidence of spinal cord or cauda equina compression, with either paraplegia or
      paraparesis. Patients underwent recapping laminoplasty in the thoracic or lumbar
      spine for decompression of spinal cord. The T-saw was used for division of the
      posterior elements. After decompression of the cord and removal of the extruded
      bone fragments and disc material, the excised laminae were replaced exactly in
      situ to their original anatomic position. Then application of a compression force
      via monosegmental transpedicular fixation was done, allowing vertebral end-plate
      compression and interbody fusion. RESULTS: Lateral Cobb angle (T(10)-L(2)) was
      reduced from 26 to 4 degrees after surgery. The shortened vertebral body united
      and no or minimal loss of correction was seen. The preoperative vertebral
      kyphosis averaged +17 degrees and was corrected to +7 degrees at follow-up with
      the sagittal index improving from 0.59 to 0.86. The segmental local kyphosis was
      reduced from +15 degrees to -3 degrees. Radiography demonstrated anatomically
      correct reconstruction in all patients, as well as solid fusion. CONCLUSION: This
      technique permits circumferential decompression of the spinal cord through a
      posterior approach and posterior interbody fusion.

PMID- 21716870
TI  - Commentary.

PMID- 21716871
TI  - Benign paroxysmal positional vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) is a common clinical disorder
      characterized by brief recurrent spells of vertigo often brought about by certain
      head position changes as may occur with looking up, turning over in bed, or
      straightening up after bending over. It is important to understand BPPV not only
      because it may avert expensive and often unnecessary testing, but also because
      treatment is rapid, easy, and effective in >90% of cases. The diagnosis of BPPV
      can be made based on the history and examination. Patients usually report
      episodes of spinning evoked by certain movements, such as lying back or getting
      out of bed, turning in bed, looking up, or straightening after bending over. At
      present, the generally accepted recurrence rate of BPPV after successful
      treatment is 40%-50% at 5 years of average follow-up. There does appear to be a
      subset of individuals prone to multiple recurrences.

PMID- 21716872
TI  - Neuroacanthocytosis: A rare movement disorder with magnetic resonance imaging.

PMID- 21716873
TI  - Cloud-like pattern of mineralization in skull base osteosarcoma.

PMID- 21716874
TI  - Correlative study between neuron-specific enolase and blood sugar level in
      ischemic stroke patients.
AB  - BACKGROUND: A study to investigate the level of the neurobiochemical marker,
      Neuron-Specific Enolase (NSE), at the time of admission and its correlation with
      the blood sugar level in ischemic stroke patients. PATIENTS AND METHODS: We
      investigated 90 patients with complete stroke who were admitted to the Stroke
      Unit of the Department of Neurology at Sri Aurobindo Institute of Medical
      Sciences. NSE was measured with commercially available quantitative 'sandwich'
      enzyme-linked immunosorbent assay kits obtained from R and D Systems.
      Hyperglycemia was defined as blood glucose concentration >= 7 mmol / L, and
      measured using the glucose oxidase method immediately. RESULTS: Significantly
      increased NSE and lipid profile levels were found in ischemic stroke patients as
      compared to the control. Hyperglycemic ischemic stroke patients had increased
      levels of NSE, lipid profile, and National Institute of Health stroke scale
      scores (NIHSS score) compared to normoglycemic ischemic stroke patients. In
      addition the serum NSE level of hyperglycemic stroke patients was also positively
      correlated with the blood sugar level (r = 0.734 P < 0.001). CONCLUSIONS:
      Hyperglycemia predicts an increased risk of poor outcome after ischemic stroke
      and it is reflected by a significantly increased level of Neuron-Specific
      Enolase.

PMID- 21716875
TI  - Tuberculous meningoencephalitis with severe neurological sequel in an immigrant
      child.
AB  - Central nervous system tuberculosis (TB) is the most devastating manifestation of
      TB. It is a challenge for clinicians because of the difficulty in making an early
      diagnosis and the severe consequences of delayed treatment. The aim of this
      report is to point out the relation between migration and TB based on a 14-year
      old child with tuberculous meningoencephalitis (TBM) of an immigrant family.
      Migration, crowded living conditions and positive family history contribute to
      the severe course of TB as TBM and miliary TB forms. TB control may prevent these
      severe manifestations of the disease among immigrants. Prompt diagnosis with
      helpful early diagnostic tools like polymerase chain reaction in TBM is crucial
      due to the high mortality and morbidity.

PMID- 21716876
TI  - Impacted calculus within a urethral stent: A rare cause of urinary retention.
AB  - An elderly male presented to the emergency department with acute urinary
      retention. He had poor flow of urine associated with serosanguinous discharge per
      urethra for 3 days duration. Earlier he underwent permanent metallic urethral
      stenting for post TURP bulbar urethral stricture. Plain X-ray of Pelvis showed an
      impacted calculus within the urethral stent in bulbar urethra. Urethrolitholapaxy
      was done with semirigid ureteroscope. Urethral stent was patent and well covered.
      Subsequently he had an uneventful recovery. We describe a unique case of acute
      urinary retention due to calculus impaction within a urethral stent.

PMID- 21716877
TI  - Breast carcinoma metastasizing to the urinary bladder and retroperitoneum
      presenting as acute renal failure.
AB  - Breast carcinoma is the most common nondermatologic cancer diagnosis in women.
      Common metastatic sites include lymph nodes, lung, liver, and bone. Breast
      carcinoma metastatic to the bladder has been reported only sporadically. Most
      patients were symptomatic breast cancer with evidence of disseminated disease at
      the time of diagnosis. Metastasis usually occurred many years after diagnosis,
      and the prognosis was poor. We report a case of breast caricinoma metastasizing
      to the urinary bladder and retroperitoneum, which presented initially with acute
      renal failure. Patient was treated with bilateral per cuteneous nephrostomies and
      chemotherapy. Starting from this clinical case we review the available literature
      on this issue. Patients with breast cancer presenting with urinary symptoms
      should be examined for possible bladder metastasis.

PMID- 21716878
TI  - Primary malignancy of seminal vesicle: A rare entity.
AB  - We report a rare case of seminal vesicle malignancy (primitive neuro ectodermal
      tumor) in a 40-year-old male patient. He was treated with enbloc resection of the
      tumor and ureteric reimplantation. In view of the rarity of this entity,
      management of these tumors should be individualized.

PMID- 21716879
TI  - Zinc status of patients with benign prostatic hyperplasia and prostate carcinoma.
AB  - OBJECTIVES: The exact cause of benign prostatic hyperplasia (BPH) and prostatic
      carcinoma is unknown. Changes in the level of the trace element zinc (Zn) are
      known to be associated with the functioning of different organs (breast, colon,
      stomach, liver, kidney, prostate, and muscle). This study is aimed at estimating
      and comparing the zinc levels in the prostate tissue, plasma, and urine obtained
      from patients diagnosed with BPH or prostatic carcinoma. MATERIALS AND METHODS:
      The prostate tissue zinc, plasma zinc, and urine zinc/creatinine ratio in BPH,
      prostate cancer, and normal subjects were measured by atomic absorption
      spectrophotometry. RESULTS: In prostate carcinoma, the mean tissue zinc was
      decreased by 83% as compared to normal tissue and in BPH, there was a 61%
      decrease in mean tissue zinc as compared to normal tissues. Both these values
      were statistically significant. The plasma zinc in prostate cancer patients
      showed a 27% decrease (P < 0.01) as compared to controls and 18% decrease (P <
      0.01) as compared to BPH. The urine zinc/creatinine (ratio) was significantly
      increased to 53% in prostate cancer patients, and a 20% significant increase was
      observed in BPH as compared to normal subjects. CONCLUSIONS: It is evident from
      this study that BPH or prostate carcinoma may be associated with a reduction in
      the levels of tissue zinc, plasma zinc, and an increase in urine zinc/creatinine.

PMID- 21716880
TI  - Mesonephric adenoma in remnant ureteric stump: A rare entity.
AB  - Nephrogenic Adenomas have been reported though out the Urinary Tract from Renal
      Pelvis to the Urethra. We present one rare case of its occurrence in the remanant
      ureteral stump.

PMID- 21716881
TI  - Giant unilateral hydrocele "en-bisac" with right hydronephrosis in an adult: A
      rare entity.
AB  - Abdominoscrotal hydrocele consists of two large sacs; the abdominal and scrotal,
      both are connected via the inguinal canal. The diagnosis is made by clinical
      examination and can be confirmed with ultrasound scan. Surgical treatment is
      considered mandatory since spontaneous resolution is extremely rare. Herein, we
      report a case of giant unilateral hydrocele en-bisac who presented with
      spontaneous rupture of the sac.

PMID- 21716882
TI  - A rare case of plasmacytoid urothelial carcinoma of bladder: Diagnostic dilemmas
      and clinical implications.
AB  - Plasmacytoid urothelial carcinoma is an uncommon and aggressive variant of
      urothelial carcinoma associated with late presentation and poor prognosis. We
      discuss here the first reported case from India of a 54-year-old male who
      presented with hematuria. Cystoscopy showed edematous and ulcerated mucosa
      throughout the bladder. A transurethral biopsy revealed urothelial carcinoma with
      plasmacytoid appearance. He underwent a radial cystectomy which on histopathology
      showed plasmacytoid urothelial carcinoma of the bladder of high stage with
      involvement up to bladder serosa and adventitial walls of the ureter. The
      diagnostic dilemmas of this unusual variant of urothelial malignancy and its
      clinical impact are discussed.

PMID- 21716883
TI  - Extra-anatomical complications of antegrade double-J insertion.
AB  - INTRODUCTION: Insertion of a double-J (JJ) stent is a common procedure often
      carried out in the retrograde route by the urologists and the antegrade route by
      the radiologists. Reported complications include stent migration, encrustation,
      and fracture. Extra-anatomic placement of an antegrade JJ stent is a rare but
      infrequently recognized complication. MATERIALS AND METHODS: We performed a
      retrospective audit of 165 antegrade JJ stent insertions performed over three
      consecutive years by a single interventional radiologist. All renal units were
      hydronephrotic at the time of nephrostomy. All procedures were performed under
      local anaesthetic with antibiotic prophylaxis. RESULTS: Antegrade stent insertion
      was carried out simultaneously at the time of nephrostomy in 55 of the 165 cases
      (33%). The remainder were inserted at a mean of 2 weeks following decompression.
      In five (3%) patients, who had delayed antegrade stenting following nephrostomy,
      the procedure was complicated by silent ureteric perforation and an extra
      anatomic placement of the stent. These complications had delayed manifestations,
      which included two retroperitoneal abscesses, a pelvic urinoma, a case each of
      ureterorectal fistula, and ureterovaginal fistula. Risk factors for ureteric
      perforation include previous pelvic malignancy, pelvic surgery, pelvic radiation,
      and a history of ureteric manipulation. CONCLUSION: Antegrade ureteric JJ
      stenting is a procedure not without complications. Extra-anatomic placement of
      the antegrade stent is a hitherto the infrequently reported complication but
      needs a high index of suspicion to be diagnosed. Risk factors for ureteric
      perforation at the time of stent insertion have to be considered to prevent this
      potential complication.

PMID- 21716884
TI  - Surgical management of upper tract urothelial carcinoma.
AB  - Upper tract urothelial cell carcinoma accounts for 5% of all urothelial tumors.
      Compared to lower urinary tract tumors, upper tract urothelial carcinoma is
      diagnosed more frequently at advanced stages. Open radical nephroureterectomy
      remains the gold standard treatment option for upper tract tumors. However, with
      the advancement of minimally invasive techniques and the benefits of these
      procedures regarding perioperative morbidity, cosmesis, and earlier
      convalescence, these options have shown promise in managing the patients with
      upper tract urothelial carcinoma. Despite the perioperative advantages, concerns
      exist on the oncological safety after minimally invasive surgery. In this
      article, we provide a comprehensive overview of the surgical management of upper
      tract urothelial carcinoma.

PMID- 21716885
TI  - Live related donors in India: Their quality of life using world health
      organization quality of life brief questionnaire.
AB  - CONTEXT: Organ selling is now legally banned in India. Numerous studies have
      documented that organ vendors have a poor quality of life (QOL) following kidney
      donation. AIMS: This study was designed to assess the QOL of living related
      donors in India. SETTINGS AND DESIGN: This study was a single-center prospective
      study. MATERIALS AND METHODS: The QOL of 106 consecutive related kidney donors
      was compared before and 6 months after the donation using the World Health
      Organisation Quality of Life Brief Questionnaire. STATISTICAL ANALYSIS USED:
      STATA 9.0 (College Station, Texas) was used and a p value less than 0.05 was
      considered significant. RESULTS: The response rate was 94.3% and the mean age was
      43.2+/-11.95 years. Females constituted 73% of the population. Our study showed a
      significant improvement in the QOL among three of the four domains. The surgical
      technique (86- mini open donor nephrectomy, and 14 laparoscopic donor
      nephrectomy), education status, and marital status did not make any difference in
      the change in the QOL. CONCLUSIONS: Despite a number of our donors being
      unemployed and not being well educated, live related kidney donation improves the
      QOL of donors.

PMID- 21716886
TI  - Dual kidney transplantation from expanded criteria deceased donors: Initial
      experience from single center.
AB  - AIM: To evaluate results of dual kidney transplantation from expanded criteria
      deceased donors. MATERIALS AND METHODS: Between January 2000 and December 2009,
      23 dual kidney transplantations were performed from expanded criteria deceased
      donors; 11 were from non-heart-beating donors and 12 from brain-dead heart
      beating donors. All transplantations were performed in monolateral iliac fossa.
      RESULTS: Two perioperative deaths occurred due to sepsis and multiorgan failure
      in non-heart-beating group, and one in brain dead group. One- and five-year graft
      and patient survival in recipients having organs from brain-death heart-beating
      group were 91.67%. In non-heart-beating group, 1- and 5-year graft survival was
      65.45% and 81.82%, and 1- and 5-year patient survival was 43.64% and 61.36%,
      respectively. CONCLUSION: Dual kidney transplantation from expanded criteria
      brain dead donors has better graft and patient survival than from non-heart
      beating donors.

PMID- 21716887
TI  - Is modified Raz technique of midurethral sling a reliable and cost-effective
      method of treating stress urinary incontinence?
AB  - OBJECTIVES: We report our experience of pure stress urinary incontinence (SUI)
      treated by midurethral synthetic sling placement by modified Raz technique.
      MATERIALS AND METHODS: Fifty-three patients with pure SUI operated at our
      institute between June 2003 and December 2008 were included in this study.
      Midurethral sling tape, fashioned from commercially available large pore
      synthetic mesh, was placed using the modified Raz technique. The technique
      consisted of placing the tape within retropubic space using double-pronged
      needle, which is passed under finger control through the fascia and retropubic
      space. Outcomes were assessed on the basis of patient's interview in follow-up
      OPD. RESULTS: Mean age was 57.68 (28-69) years. Forty-five (85%) patients were
      totally dry and eight (15%) socially dry at the end of the follow-up. Mean
      operative time was 46.5 + 11.3 minutes (35-80 minutes). None of the patients
      required blood transfusion or had bladder/bowel injury. Mean duration of hospital
      stay was 2.17 days (2-4 days). Mean duration of follow-up was 46.1 months (12-78
      months). CONCLUSIONS: Modified Raz technique is safe and cost-effective for
      placing midurethral sling for genuine stress incontinence.

PMID- 21716888
TI  - Male infertility - Current concepts.

PMID- 21716889
TI  - Semen analysis and sperm function tests: How much to test?
AB  - Semen analysis as an integral part of infertility investigations is taken as a
      surrogate measure for male fecundity in clinical andrology, male fertility, and
      pregnancy risk assessments. Clearly, laboratory seminology is still very much in
      its infancy. In as much as the creation of a conventional semen profile will
      always represent the foundations of male fertility evaluation, the 5th edition of
      the World Health Organization (WHO) manual is a definitive statement on how such
      assessments should be carried out and how the quality should be controlled. A
      major advance in this new edition of the WHO manual, resolving the most salient
      critique of previous editions, is the development of the first well-defined
      reference ranges for semen analysis based on the analysis of over 1900 recent
      fathers. The methodology used in the assessment of the usual variables in semen
      analysis is described, as are many of the less common, but very valuable, sperm
      function tests. Sperm function testing is used to determine if the sperm have the
      biologic capacity to perform the tasks necessary to reach and fertilize ova and
      ultimately result in live births. A variety of tests are available to evaluate
      different aspects of these functions. To accurately use these functional assays,
      the clinician must understand what the tests measure, what the indications are
      for the assays, and how to interpret the results to direct further testing or
      patient management.

PMID- 21716890
TI  - Guideline-based management of male infertility: Why do we need it?
AB  - The current clinical guidelines for the management of infertility as presented by
      the American Urologic Association and European Association of Urology represent
      consensus opinions for the management of male-factor infertility. The goal of the
      present study is to define the currently available guidelines for male-factor
      infertility, provide a rationale for why guidelines should be implemented, and
      review concerns and shortcomings towards their incorporation into clinical
      practice. Successfully integrating guidelines into clinical practice offers the
      potential benefit of creating a standardized, efficient, and cost-effective
      algorithm for the evaluation of infertility and facilitates future research.
      Despite their availability and ease of use, many clinicians fail to adopt
      clinical guidelines for numerous reasons including decreased awareness of
      available guidelines, insufficient time, lack of interest, and personal financial
      considerations. The current guidelines are limited by the inability to generalize
      recommendations to a heterogeneous patient sample, the lack of interdisciplinary
      adoption of guidelines, and the need for additional emphasis on prevention and
      lifestyle modifications. Future direction for the current guidelines will likely
      incorporate a multidisciplinary approach with increasing utilization of genetic
      analysis and novel treatment strategies. As the field of infertility continues to
      expand, the utility of guidelines combined with physician clinical judgment will
      remain prominent in the treatment of male-factor infertility.

PMID- 21716891
TI  - Varicocele-induced infertility: Newer insights into its pathophysiology.
AB  - The association between varicoceles and male infertility has been known since the
      1950s; however, the pathophysiology of the process remains uncertain. The primary
      proposed hypotheses involve hyperthermia, venous pressure, testicular blood flow,
      hormonal imbalance, toxic substances, and reactive oxygen species. It is
      difficult to identify a single or dominant factor, and it is likely that many of
      these factors contribute to the infertile phenotype seen in clinical practice.
      Moreover, patient lifestyle and genetic factors likely affect patient
      susceptibilities to the varicocele insult. While the current studies have
      weaknesses, they provide building blocks for futures studies into the
      pathophysiology of the varicocele.

PMID- 21716892
TI  - Management options of varicoceles.
AB  - Varicocele is one of the most common causes of male infertility. Treatment
      options for varicoceles includes open varicocelectomy performed at various
      anatomical levels. Laparoscopic varicocelectomy has been established to be a safe
      and effective treatment for varicoceles. Robotic surgery has been introduced
      recently as an alternative surgical option for varicocelectomy. Microsurgical
      varicocelectomy has gained increasing popularity among experts in male
      reproductive medicine as the treatment of choice for varicocele because of its
      superior surgical outcomes. There is a growing volume of literature in the recent
      years on minimal invasive varicocele treatment with percutaneous retrograde and
      anterograde venous embolization/sclerotherapy. In this review, we will discuss
      the advantages and limitations associated with each treatment modality for
      varicoceles. Employment of these advanced techniques of varicocelectomy can
      provide a safe and effective approach aiming to eliminate varicocele, preserve
      testicular function and, in a substantial number of men, increase semen quality
      and the likelihood of pregnancy.

PMID- 21716894
TI  - Vasectomy and vasectomy reversal: An update.
AB  - Vasectomy is an elective surgical sterilization procedure for men that is
      intended to obstruct or remove a portion of both vas deferens, thereby preventing
      sperm from moving from the testes to the ejaculatory ducts. Although intended for
      permanent sterilization, vasectomy can be reversed in most men seeking to restore
      their fertility due to a change in marital status or reproductive goals. The
      purpose of this document is to provided a synopsis of the latest techniques used
      in vasectomy and reversal.

PMID- 21716893
TI  - Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it
      justified?
AB  - Oxidative stress contributes to defective spermatogenesis and the poor quality of
      sperm associated with idiopathic male factor infertility. The aim of this study
      was to review the current literature on the effects of various types of
      antioxidant supplements in patients to improve fertilization and pregnancy rates
      in subfertile males with idiopathic oligoasthenoteratozoospermia (iOAT). Review
      of recent publications through PubMed and the Cochrane database. Oxidative stress
      is implicated in impaired spermatogenesis leading to the poor semen parameters
      and increased DNA damage and apoptosis in iOAT. Strategies to modulate the level
      of oxidative stress within the male reproductive tract include the use of oral
      antioxidant compounds to reinforce the body's defence against oxidative damage.
      In our evaluation, carnitines were considered the most established
      pharmacotherapeutic agent to treat iOAT, as evidence and data concerning
      carnitine supplementation have been shown to be most consistent and relevant to
      the population of interest. Other therapies, such as combined vitamin E and C
      therapy, are still considered controversial as vitamin C can act as a pro-oxidant
      in certain instances and the results of randomized controlled trials have failed
      to show significant benefit to sperm parameters and pregnancy rates. There is a
      need for further investigation with randomized controlled studies to confirm the
      efficacy and safety of antioxidant supplementation in the medical treatment of
      idiopathic male infertility as well as the need to determine the dosage required
      to improve semen parameters, fertilization rates and pregnancy outcomes in iOAT.

PMID- 21716895
TI  - Surgery for azoospermia in the Indian patient: Why is it different?
AB  - Obstructive azoospermia is one of the few surgically correctable causes of male
      infertility. The outcomes of surgery in these patients are variable and often
      dependent upon the diagnosis and surgical expertise. We aimed to review the
      reported outcomes in Indian patients and evaluate potential reasons why these
      outcomes may be different from those reported from other regions. A search was
      performed on Medline/Pubmed using relevant keywords to identify publications from
      India on surgical management of azoospermia. The same search was repeated on
      Google and on the website of the Indian Journal of Urology. Personal emails were
      sent to prominent urologists performing surgery for azoospermia in India to
      obtain their opinions and reprints of their published articles. These were then
      reviewed. Very few articles were identified that pertained to the original
      search. A large majority of patients are diagnosed with idiopathic infertility.
      The outcomes of surgery where a clear diagnosis can be made are generally good
      and often comparable with the published literature. Infections are probably an
      under-diagnosed etiology. More research and publications are required to
      determine the etiology of obstructive azoospermia in the Indian men. These would
      help appropriate patient counseling and treatment.

PMID- 21716896
TI  - The Efficacy of Simultaneous Bilateral Internal Carotid Angiography during Coil
      Embolization for Anterior Communicating Artery Aneurysms.
AB  - OBJECTIVE: Successful coil embolization of anterior communicating (A-com) artery
      aneurysms requires good visualization and understanding of the entire H complex.
      Bilateral carotid angiography may optimize anatomical understanding and
      visualization of the H complex. We therefore assessed the efficacy of
      simultaneous bilateral internal carotid angiography during coil embolization for
      A-com artery aneurysms. METHODS: Of the 153 patients with intracranial saccular
      aneurysms who underwent embolization between July 2008 and December 2009, 12 had
      A-com artery aneurysms and were embolized under bilateral carotid angiography.
      Patients were evaluated angiographically, immediately and 6 months (n=11) after
      embolization, using a 3-point scale (complete, residual neck, residual aneurysm).
      The safety, performance and efficacy of this approach were retrospectively
      evaluated. RESULTS: In all patients, bilateral internal carotid artery
      angiography provided more detailed anatomical information and understanding
      around the A-com artery, and, in complex situations, it allowed for more
      effective coil embolization through bilateral routes to the A-com artery.
      Angiography immediately after embolization showed occlusion of 11 of the 12 (92%)
      aneurysms, with none of these 11 showing evidence of recanalization at 6 months.
      CONCLUSION: These findings indicate that simultaneous bilateral carotid
      angiography during coil embolization of selected complex A-com artery aneurysms
      provided improved anatomical understanding, and resulted in more effective and
      safer procedures than typical unilateral angiography.

PMID- 21716897
TI  - Technical considerations to prevent postoperative endocrine dysfunction after the
      fenestration of suprasellar arachnoid cyst.
AB  - OBJECTIVE: The endocrine dysfunction after the operation for suprasellar
      arachnoid cysts is not rare. The careful operation to prevent structures can
      prevent this complication, but it is not enough and effective to prevent it.
      Authors present technical surgical considerations to prevent this complication
      with a review of our suprasellar arachnoid cyst patients who had postoperative
      endocrine dysfunction. METHODS: From January 2002 to December 2009, eight
      patients who had suprasellar arachnoid cysts with visual impairment underwent
      surgery. The mean age was 57.1 years (range, 33-77). Preoperatively, their
      endocrine function was clinically normal, and laboratory hormonal levels were
      within normal ranges. Cyst fenestration was performed by craniotomy (n=6) or by a
      neuro-endoscopic procedure (n=2), and, simultaneously, along with a cyst wall
      biopsy. RESULTS: The surgery was uneventful in all eight patients, and there were
      no neurological morbidities. However, in four patients, endocrine dysfunction
      occurred postoperatively. We compared these four patients (group A) to the other
      4 patients without endocrine dysfunction (group B) with intraoperative findings
      and with the histopathological findings of the cyst wall biopsy. The group A
      patients had more abundant vasculature on the cystic wall than the group B
      patients according to both the intraoperative findings and the histopathological
      findings. CONCLUSION: When performing a surgical cyst wall fenestration, surgeons
      should try to minimize the destruction of the cystic wall vasculature and not to
      make the fenestration at a site that contains many vascular striae.

PMID- 21716898
TI  - Radiographic Analysis of Instrumented Posterolateral Fusion Mass Using Mixture of
      Local Autologous Bone and b-TCP (PolyBone(r)) in a Lumbar Spinal Fusion Surgery.
AB  - OBJECTIVE: Although iliac crest autograft is the gold standard for lumbar fusion,
      the morbidity of donor site leads us to find an alternatives to replace
      autologous bone graft. Ceramic-based synthetic bone grafts such as hydroxyapatite
      (HA) and b-tricalcium phosphate (b-TCP) provide scaffolds similar to those of
      autologous bone, are plentiful and inexpensive, and are not associated with donor
      morbidity. The present report describes the use of Polybone(r) (Kyungwon Medical,
      Korea), a beta-tricalcium phosphate, for lumbar posterolateral fusion and
      assesses clinical and radiological efficacy as a graft material. METHODS: This
      study retrospectively analyzed data from 32 patients (11 men, 21 women) who
      underwent posterolateral fusion (PLF) using PolyBone(r) from January to August,
      2008. Back and leg pain were assessed using a Numeric Rating Scale (NRS), and
      clinical outcome was assessed using the Oswestry Disability Index (ODI). Serial
      radiological X-ray follow up were done at 1, 3, 6 12 month. A computed tomography
      (CT) scan was done in 12 month. Radiological fusion was assessed using simple
      anterior-posterior (AP) X-rays and computed tomography (CT). The changes of
      radiodensity of fusion mass showed on the X-ray image were analyzed into 4 stages
      to assess PLF status. RESULTS: The mean NRS scores for leg pain and back pain
      decreased over 12 months postoperatively, from 8.0 to 1.0 and from 6.7 to 1.7,
      respectively. The mean ODI score also decreased from 60.5 to 17.7. X-rays and CT
      showed that 25 cases had stage IV fusion bridges at 12 months postoperatively
      (83.3% success). The radiodensity of fusion mass on X-ray AP image significantly
      changed at 1 and 6 months. CONCLUSION: The present results indicate that the use
      of a mixture of local autologous bone and PolyBone(r) results in fusion rates
      comparable to those using autologous bone and has the advantage of reduced
      morbidity. In addition, the graft radiodensity ratio significantly changed at
      postoperative 1 and 6 months, possibly reflecting the inflammatory response and
      stabilization.

PMID- 21716899
TI  - Unilateral extrapedicular vertebroplasty and kyphoplasty in lumbar compression
      fractures : technique, anatomy and preliminary results.
AB  - OBJECTIVE: A single balloon extrapedicular kyphoplasty has been introduced as one
      of the unilateral approaches for thoracic compression fractures; however, the
      unilateral extrapedicular technique in the lumbar area needs a further
      understanding of structures in the lumbar area. The purpose of the present study
      is to describe methods and pitfalls of this procedure based on the anatomy of the
      lumbar area and to analyze clinical outcome and complications. METHODS:
      Anatomical evaluation was performed with 2 human cadavers. A retrospective review
      of unilateral extrapedicular approaches yielded 74 vertebral levels in 55
      patients that were treated with unilateral extrapedicular vertebroplasty and
      kyphoplasty. Radiographic assessment included the restoration rate of vertebral
      height and correction of kyphosis. RESULTS: Anatomical evaluation indicates that
      the safe needle entry zone of bone for the extrapedicular approach was located in
      the supero-lateral aspect of the junction between the pedicle and vertebral body.
      The unilateral extrapedicular procedure achieved adequate pain relief with a mean
      decreases in pain severity of 7.25+/-1.5 and 2.0+/-1.4, respectively.
      Complications were 1 retroperitoneal hematoma, 6 unilateral fillings and 3
      epidural leak of the polymethylmethacrylate. CONCLUSION: The method of a
      unilateral extrapedicular approach in kyphoplasty and vertebroplasty in the
      lumbar area might be similar to that in thoracic approach using a route via the
      extrapedicular space. However, different anatomical characteristics of the lumbar
      area should be considered.

PMID- 21716900
TI  - The role of f-fluorodeoxyglucose positron emission tomography in the treatment of
      brain abscess.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether (18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) can be used to assess
      the therapeutic response of brain abscess. METHODS: A study was conducted on 10
      consecutive patients with brain abscess. Magnetic resonance imaging (MRI) with
      diffuse-weighted imaging (DWI) was performed at 3 and 6 weeks after surgical
      treatment and intravenous antibiotics therapy and FDG-PET at 6 weeks after
      treatment. The extent of the abscess, signal changes on MRI, and FDG-PET
      standardized uptake values were analyzed and correlated with the response to
      therapy. RESULTS: Aspiration or craniotomy with excision of the abscess followed
      by intravenous antibiotics for 6-8 weeks resulted in good recovery with no
      recurrence. In 10 patients, two had low signal intensity on the DWI; one had no
      uptake on FDG-PET imaging after 6 weeks antibiotics and discontinued intravenous
      treatment, but the other patient had diffuse, increased uptake on FDG-PET imaging
      after 6 weeks antibiotics and underwent an additional 2 weeks of intravenous
      antibiotics. The remaining eight patients had high signals on the DWI. Four had
      no uptake on FDG-PET imaging and the treatment period varied from 6 to 8 weeks
      (mean, 6.75 weeks). Among the other four patients, FDG was accumulated in a
      diffuse or local area corresponding to a high signal area within the DWI and 2
      weeks of intravenous antibiotics was added. CONCLUSION: MRI plus FDG-PET improved
      the accuracy of assessing therapeutic responses to antibiotics treatment of brain
      abscess and aided in optimizing therapy.

PMID- 21716901
TI  - Glossopharyngeal neuralgia caused by arachnoid cyst in the cerebellopontine
      angle.
AB  - Glossopharyngeal neuralgia is a relatively rare condition characterized by
      severe, paroxysmal episodes of lancinating pain in the tongue, throat, ear, and
      tonsil. This disorder is assumed to be due to compression of the glossopharyngeal
      nerve by vascular structures. A 47-year-old woman complaining of sharp and
      lancinating pain in the right periauricular and submandibular areas visited our
      hospital. Swallowing, chewing, and lying on her right side triggered the pain.
      Her neurologic examination revealed no specific abnormalities. The results of
      routine hematologic and blood chemistry studies were all within normal limits.
      Carbamazepine and gabapentin were given, but her symptoms persisted. Her pain was
      temporarily relieved only by narcotic pain medication. MRI showed an arachnoid
      cyst located in the right cerebellomedullary cistern extending to the
      cerebellopontine cistern. Cyst removal was performed via a right retrosigmoid
      approach. Lateral suboccipital craniotomy was performed using the right park
      bench position. After opening the dura and cerebellopontine angle, the arachnoid
      cyst was exposed. The arachnoid cyst was compressing the flattened lower cranial
      nerves at the right jugular fossa. Her symptoms resolved postoperatively. Two
      months after the operation, she was completely free from her previous symptoms.

PMID- 21716902
TI  - Glue embolization of ruptured anterior thalamoperforating artery aneurysm in
      patient with both internal carotid arteries occlusion.
AB  - Thalamoperforating artery aneurysms are rarely reported in the literature. We
      report an extremely rare case of ruptured distal anterior thalamoperforating
      artery aneurysm which was treated by endovascular obliteration in a patient with
      occlusion of both the internal carotid arteries (ICAs) : A 72-year-old woman
      presented with severe headache and loss of consciousness. Initial level of
      consciousness at the time of admission was drowsy and the Glasgow Coma Scale
      score was 14. Brain computed tomography (CT) scan was performed which revealed
      intracerebral hemorrhage in right basal ganglia, subarachnoid hemorrhage, and
      intraventricular hemorrhage. The location of the aneurysm was identified as
      within the globus pallidus on CT angiogram. Conventional cerebral angiogram
      demonstrated occlusion of both the ICAs just distal to the fetal type of
      posterior communicating artery and the aneurysm was arising from right anterior
      thalamoperforating artery (ATPA). A microcatheter was navigated into ATPA and the
      ATPA proximal to aneurysm was embolized with 20% glue. Post-procedural ICA
      angiogram demonstrated no contrast filling of the aneurysm sac. The patient was
      discharged without any neurologic deficit. Endovascular treatment of ATPA
      aneurysm is probably a more feasible and safe treatment modality than surgical
      clipping because of the deep seated location of aneurysm and the possibility of
      brain retraction injury during surgical operation.

PMID- 21716903
TI  - In vitro study on apoptosis induced by strontium-89 in human breast carcinoma
      cell line.
AB  - Many radiopharmaceuticals used for medical diagnosis and therapy are beta
      emitters; however, the mechanism of the cell death caused by beta-irradiation is
      not well understood. The objective of this study was to investigate the apoptosis
      of human breast carcinoma MCF-7 cell lines induced by Strontium-89 (89Sr) and its
      regulation and control mechanism. High-metastatic Breast Carcinoma MCF-7 cells
      were cultured in vitro using 89Sr with different radioactive concentration. The
      inhibition rate of cell proliferation was measured by MTT color matching method.
      The cell cycle retardation, apoptosis conditions, mitochondrion transmembrane
      potential difference and Fas expression were tested and analyzed. The genes P53
      and bcl-2 expressions was also analyzed using immunity histochemical analysis.
      After being induced by 89Sr with various of radioactive concentration, it was
      found that the inhibition of cell proliferation of MCF-7 cells was obviously, the
      retardation of cell cycle occurred mainly in G2-M. It was also found that the
      obvious apoptosis occurred after being induced by 89Sr, the highest apoptosis
      rate reached 46.28%. The expressions of Fas acceptor and P53 gene increased,
      while bcl-2 gene expression decreasesd. These findings demonstrate that in the
      ranges of a certain radioactive concentration, the inhibition rate of MCF-7 cell
      proliferation and retardation of cell cycle had positive correlation with the
      concentration of 89Sr. And the mitochondrion transmembrane potential decrease
      would induce the apoptosis of MCF-7 cell notably, which were controlled by P53
      and bcl-2 genes, involved with the Fas acceptor.

PMID- 21716904
TI  - Variability in estrogen-metabolizing genes and their association with genomic
      instability in untreated breast cancer patients and healthy women.
AB  - In the present study, we investigated the relationship between polymorphisms in
      the estrogen-metabolizing genes CYP17, CYP1B1, CYP1A1, and COMT and genomic
      instability in the peripheral blood lymphocytes of 62 BC patients and 62 controls
      considering that increased or prolonged exposure to estrogen can damage the DNA
      molecule and increase the genomic instability process in breast tissue. Our data
      demonstrated increased genomic instability in BC patients and that individuals
      with higher frequencies of MN exhibited higher risk to BC when belonging Val/Met
      genotype of the COMT gene. We also observed that CYP17 and CYP1A1 polymorphisms
      can modify the risk to BC depending on the menopause status. We can conclude that
      the genetic background in estrogen metabolism pathway can modulate chromosome
      damage in healthy controls and patients and thereby influence the risk to BC.
      These findings suggest the importance to ally biomarkers of susceptibility and
      effects to estimate risk groups.

PMID- 21716905
TI  - Primary mucinous adenocarcinoma of the vermiform appendix with high grade
      microsatellite instability.
AB  - Primary adenocarcinoma of the vermiform appendix is a rare entity and is
      frequently discovered by the pathologist following appendectomy for suspected
      appendicitis.We present a 42-year-old male with primary mucinous adenocarcinoma
      of the appendix initially presenting symptoms of acute appendicitis. Histological
      investigation of the appendectomy specimen showed a mucinous adenocarcinoma and
      the patient was treated by secondary right hemicolectomy giving the final
      histopathological classification of an UICC IIIC tumor. Since the patient
      fulfills the revised Bethesda criteria analysis of immunoreactivity of DNA
      mismatch repair proteins was performed showing loss of MLH1 and MSH2 expression
      associated with high microsatellite instability (MSI-H), not yet reported for
      primary mucinous appendiceal carcinoma. Further genetic analysis for DNA mismatch
      repair gene mutations were negative. The patient received intensified adjuvant
      chemotherapy according to the FOLFOX-4-scheme, since MSI-H colorectal carcinomas
      might show lower response rates following standard 5-FU-based adjuvant
      chemotherapy.

PMID- 21716906
TI  - A comparative study on the usefulness of the Glidescope or Macintosh laryngoscope
      when intubating normal airways.
AB  - BACKGROUND: The Glidescope Videolaryngoscope (GVL) is a newly developed video
      laryngoscope. It offers a significantly improved laryngeal view and facilitates
      endotracheal intubation in difficult airways, but it is controversial in that it
      offers an improved laryngeal view in normal airways as well. And the price of GVL
      is expensive. We hypothesized that intubation carried out by fully experienced
      anesthesiologists using the GVL with appropriate pre-anesthetic preparations
      offers an improved laryngeal view and shortened intubation time in normal
      airways. Therefore, the aim of this study was to compare the GVL with the
      Macintosh laryngoscope in normal airways and to determine whether GVL can
      substitute the Macintosh laryngoscope. METHODS: This study included 60 patients
      with an ASA physical status of class 1 or 2 requiring tracheal intubation for
      elective surgery. All patients were randomly allocated into two groups, GVL
      (group G) or Macintosh (group M). ADS (airway difficulty score) was recorded
      before induction of anesthesia. The anesthesiologist scored vocal cord
      visualization using the percentage of glottic opening (POGO) visible and the
      subjective ease of intubation on a visual analogue scale (VAS). The time required
      to intubate was recorded by an assistant. RESULTS: There was a significant
      increase in POGO when using the GVL (P < 0.05). However, there was no difference
      in the time required for a successful tracheal intubation using the GVL compared
      with the Macintosh laryngoscope. The VAS score on the ease of intubation was
      significantly lower for the GVL than for the Macintosh laryngoscope (P < 0.05).
      CONCLUSIONS: GVL could be a first-line tool in normal airways.

PMID- 21716907
TI  - Intravenous fentanyl during shoulder arthroscopic surgery in the sitting position
      after interscalene block increases the incidence of episodes of bradycardia
      hypotension.
AB  - BACKGROUND: Episodes of bradycardia hypotension (BH) or vasovagal syncope have a
      reported incidence of 13-29% during arthroscopic shoulder surgery in the sitting
      position after an interscalene block (ISB). This study was designed to
      investigate whether intravenous fentanyl during shoulder arthroscopy in the
      sitting position after ISB would increase or worsen the incidence of BH episodes.
      METHODS: In this prospective study, 20 minutes after being in a sitting position,
      160 patients who underwent ISB were randomized to receive saline (S, n = 40), 50
      ug of fentanyl (F-50, n = 40), 100 ug of fentanyl (F-100, n = 40) or 30 mg of
      ketorolac (K-30, n = 40) randomly. We assessed the incidence of BH episodes
      during the operation and the degree of maximal reduction (Rmax) of blood pressure
      (BP) and heart rate (HR). RESULTS: The incidence of BH episodes was 10%, 15%,
      27.5% and 5% in the S, F-50, F-100 and K-30 groups, respectively. Mean Rmax of
      systolic BP in the F-100 group was significantly decreased as compared to the S
      group (-20.0 +/- 4.5 versus -6.3 +/- 1.6%, P = 0.004). Similarly, mean Rmax of
      diastolic BP in the F-100 group was also significantly decreased (P = 0.008) as
      compared to the S group. CONCLUSIONS: These results suggest that fentanyl can
      increase the incidence of BH episodes during shoulder arthroscopic surgery in the
      sitting position after ISB.

PMID- 21716908
TI  - Kappa-opioid receptor activation during reperfusion limits myocardial infarction
      via ERK1/2 activation in isolated rat hearts.
AB  - BACKGROUND: We investigated whether p42/p44 extracellular signal-regulated
      kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a
      crucial role in cardioprotection by kappa-opioid receptor (KOP) activation.
      METHODS: Langendorff perfused rat hearts were subjected to 30 min of regional
      ischemia and 2 h of reperfusion. Antagonists of ERK1/2 and PI3K were perfused in
      hearts treated with the KOP agonist U50488H (U50). Infarct size was measured
      after 2 h of reperfusion. The phosphorylation states of ERK1/2 and Akt by Western
      immunoblots were determined. Drugs were perfused for a period of 5 min before and
      30 min after reperfusion. RESULTS: Inhibition of ERK1/2 (26.8 +/- 2.9%, P < 0.05
      vs. U50) but not PI3K (15.5 +/- 1.1%, P > 0.05 vs. U50) completely abrogated the
      anti-infarct effect of U50488H. Western blot analysis revealed a significant
      increase in ERK1/2 but not Akt phsophorylation in U50488H-treated hearts as
      compared to control hearts when measured immediately after reperfusion.
      CONCLUSIONS: KOP activation effectively reduces myocardial infarction. The anti
      infarct effect of U50488H is mediated by the ERK1/2, but not the PI3K-Akt
      pathway.

PMID- 21716909
TI  - Cultured human chromaffin cells grafted in spinal subarachnoid space relieves
      allodynia in a pain rat model.
AB  - BACKGROUND: Implantation of xenogenic chromaffin cells into the spinal
      subarachnoid space can produce analgesia in neuropathic pain models. However,
      transplantation of xenogeneic chromaffin cell has a potential risk of viral or
      bacterial infections from animals to humans including encephalopathy due to prion
      transmission. The aim of this study was to investigate the possibility of
      developing a homogeneic source of therapeutic chromaffin cells. METHODS: Anti
      allodynic effects of human chromaffin cells (HCCs) were evaluated in a
      neuropathic pain model in rats induced by chronic constriction injury of the
      sciatic nerve. HCCs encapsulated with alginate-poly-L-lysine-alginate were
      intrathecally implanted into rats (n = 10), while empty capsules were
      intrathecally implanted as a control (n = 8). Levels of norepinephrine from
      encapsulated HCCs before and after nicotinic stimulation were measured. We then
      perfomed a behavior test (cold allodynia) with acetone. In addition, to assess
      the potential contribution to pain reduction of opioid peptides released from the
      HCCs, all animals were injected with naloxone. RESULTS: The concentration of
      norepinephrine after nicotine stimulation was significantly increased compared to
      basal levels. Intrathecal implantation of encapsulated HCCs, significantly
      reduced cold allodynia as compared to rats receiving empty capsules (P < 0.05).
      Fifteen minutes after the injection of naloxone, cold allodynia significantly
      decreased in rats with HCCs (P < 0.05), while the degree of cold allodynia in
      control animals was unaltered. CONCLUSIONS: From these results, it appears that
      HCCs have a possibility as an analgesic source for transplants delivering pain
      reducing neuroactive substances.

PMID- 21716910
TI  - Usefulness of C-reactive protein for evaluating clinical outcomes in cirrhotic
      patients with bacteremia.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the value of initial C
      reactive protein (CRP) as a predictor of clinical outcome and to investigate
      whether follow-up CRP measurement is useful for the prediction of the clinical
      outcome of bloodstream infections in patients with liver cirrhosis (LC), whose
      CRP production in response to infection may be attenuated. METHODS: A
      retrospective, observational study including 202 LC patients with Escherichia
      coli or Klebsiella pneumoniae bacteremia was conducted to assess the usefulness
      of serial CRP measurements in predicting clinical outcome in LC patients. The CRP
      ratio was defined as the ratio of the follow-up CRP level to the initial CRP
      level. RESULTS: The overall 30-day mortality rate of the study population was
      23.8% (48/202). In the multivariate analysis, advanced age (>= 70 years),
      healthcare-associated or nosocomial infections, model for end-stage liver disease
      (MELD) score of >= 30, and initial body temperature of < 37C were significant
      factors associated with mortality (all p < 0.05). No association between initial
      CRP level and mortality was found. In a further analysis including 87 evaluable
      cases who had repeated CRP measurements at day 4 and/or 5, a CRP ratio of >= 0.7
      was found to be a significant factor associated with mortality (odds ratio,
      19.12; 95% confidence interval, 1.32 to 276.86; p = 0.043) after adjusting for
      other confounding variables. CONCLUSIONS: Initial CRP level did not predict
      mortality of sepsis in LC patients. However, serial CRP measurements during the
      first week of antimicrobial therapy may be useful as a prognostic factor for
      mortality in LC patients.

PMID- 21716911
TI  - Application of helical tomotherapy for two cases of advanced hepatocellular
      carcinoma.
AB  - The role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) has
      been limited to date, because the liver has a low tolerance to radiation.
      However, reconstructing tumors and surrounding organs via a three-dimensional
      conformal planning system can avoid excess radiotherapy exposure to the rest of
      the liver and adjacent organs. Recently, the concept of "adaptive radiotherapy,"
      such as with helical tomotherapy, has been introduced for treating HCC. Helical
      tomotherapy obtains an image from the computed tomography component, which allows
      targeted regions to be visualized prior to, during, and immediately after each
      treatment and delivers intensity-modulated radiation therapy. We report two
      patients with advanced HCC who underwent tomotherapy treatment. One was a patient
      afflicted with advanced HCC and a portal vein tumor thrombus, which was treated
      with tomotherapy combined with transarterial chemolipiodolization. The other was
      a patient afflicted with multiple pulmonary metastases treated with tomotherapy
      followed by systemic chemotherapy.

PMID- 21716912
TI  - Primary small cell carcinoma of the lung presenting with breast and skin
      metastases.
AB  - Cutaneous metastases originating from an internal cancer are relatively uncommon
      in clinical practice, and metastatic lesions to the breast are rarer than those
      to the skin. Skin metastases of lung cancer, which may be the first sign of the
      disease, usually indicate progressive disease and a poor prognosis. We describe a
      47-year-old male who presented with recurring masses in the lumbar region
      bilaterally and the right breast. Immunohistochemical findings and radiological
      imaging suggested lung cancer. This is the first reported case of small cell lung
      cancer metastasizing to two separate, uncommon sites, the skin and breast.

PMID- 21716913
TI  - False-positive hypermetabolic lesions on post-treatment PET-CT after influenza
      vaccination.
AB  - We report a case of a 59-year-old man with testicular germ cell tumor who showed
      new hypermetabolic lesions at the left axillary lymph nodes on a post-treatment
      positron emission tomography-computed tomography (PET-CT) scan. The
      hypermetabolic lesions were found to be caused by an influenza vaccination 10
      days prior to the PET-CT scan and disappeared without additional treatment. To
      date, he is alive with complete remission.

PMID- 21716914
TI  - Complete atrioventricular block in adult Sjogren's syndrome with anti-Ro
      autoantibody.
AB  - Anti-Ro autoantibody is associated with Sjogren's syndrome (SS), systemic lupus
      erythematosus (SLE), and neonatal lupus syndrome (i.e., congenital complete heart
      block in newborns). Generally, the adult atrioventricular (AV) node is believed
      to be relatively resistant to the scarring effects of anti-Ro/anti-La
      autoantibodies. However, there have been some reports of adult complete AV block
      in SS and SLE patients. Here, we report a case of complete heart block in primary
      SS with anti-Ro autoantibodies, with no other risk factor for the development of
      heart block, and review their etiological association.

PMID- 21716915
TI  - A case of coarctation of the aorta diagnosed by Tardus-Parvus renal Doppler flow
      patterns.

PMID- 21716916
TI  - Ectopic thyroid nodule in thyroglossal duct.

PMID- 21716919
TI  - "Kataptation" or the qwerty-effect in language evolution.

PMID- 21716920
TI  - Regarding reality: some consequences of two incapacities.
AB  - By what empirical means can a person determine whether he or she is presently
      awake or dreaming? Any conceivable test addressing this question, which is a
      special case of the classical metaphysical doubting of reality, must be
      statistical (for the same reason that empirical science is, as noted by Hume).
      Subjecting the experienced reality to any kind of statistical test (for instance,
      a test for bizarreness) requires, however, that a set of baseline measurements be
      available. In a dream, or in a simulation, any such baseline data would be
      vulnerable to tampering by the same processes that give rise to the experienced
      reality, making the outcome of a reality test impossible to trust. Moreover,
      standard cryptographic defenses against such tampering cannot be relied upon,
      because of the potentially unlimited reach of reality modification within a
      dream, which may range from the integrity of the verification keys to the
      declared outcome of the entire process. In the face of this double predicament,
      the rational course of action is to take reality at face value. The predicament
      also has some intriguing corollaries. In particular, even the most revealing
      insight that a person may gain into the ultimate nature of reality (for instance,
      by attaining enlightenment in the Buddhist sense) is ultimately unreliable, for
      the reasons just mentioned. At the same time, to adhere to this principle, one
      has to be aware of it, which may not be possible in various states of reduced or
      altered cognitive function such as dreaming or religious experience. Thus, a
      subjectively enlightened person may still lack the one truly important piece of
      the puzzle concerning his or her existence.

PMID- 21716917
TI  - Evidence-based guidelines for empirical therapy of neutropenic fever in Korea.
AB  - Neutrophils play an important role in immunological function. Neutropenic
      patients are vulnerable to infection, and except fever is present, inflammatory
      reactions are scarce in many cases. Additionally, because infections can worsen
      rapidly, early evaluation and treatments are especially important in febrile
      neutropenic patients. In cases in which febrile neutropenia is anticipated due to
      anticancer chemotherapy, antibiotic prophylaxis can be used, based on the risk of
      infection. Antifungal prophylaxis may also be considered if long-term neutropenia
      or mucosal damage is expected. When fever is observed in patients suspected to
      have neutropenia, an adequate physical examination and blood and sputum cultures
      should be performed. Initial antibiotics should be chosen by considering the risk
      of complications following the infection; if the risk is low, oral antibiotics
      can be used. For initial intravenous antibiotics, monotherapy with a broad
      spectrum antibiotic or combination therapy with two antibiotics is recommended.
      At 3-5 days after beginning the initial antibiotic therapy, the condition of the
      patient is assessed again to determine whether the fever has subsided or symptoms
      have worsened. If the patient's condition has improved, intravenous antibiotics
      can be replaced with oral antibiotics; if the condition has deteriorated, a
      change of antibiotics or addition of antifungal agents should be considered. If
      the causative microorganism is identified, initial antimicrobial or antifungal
      agents should be changed accordingly. When the cause is not detected, the initial
      agents should continue to be used until the neutrophil count recovers.

PMID- 21716921
TI  - Increased intra-participant variability in children with autistic spectrum
      disorders: evidence from single-trial analysis of evoked EEG.
AB  - Intra-participant variability in clinical conditions such as autistic spectrum
      disorder (ASD) is an important indicator of pathophysiological processing. The
      data reported here illustrate that trial-by-trial variability can be reliably
      measured from EEG, and that intra-participant EEG variability is significantly
      greater in those with ASD than in neuro-typical matched controls. EEG recorded at
      the scalp is a linear mixture of activity arising from muscle artifacts and
      numerous concurrent brain processes. To minimize these additional sources of
      variability, EEG data were subjected to two different methods of spatial
      filtering. (i) The data were decomposed using infomax independent component
      analysis, a method of blind source separation which un-mixes the EEG signal into
      components with maximally independent time-courses, and (ii) a surface Laplacian
      transform was performed (current source density interpolation) in order to reduce
      the effects of volume conduction. Data are presented from 13 high functioning
      adolescents with ASD without co-morbid ADHD, and 12 neuro-typical age-, IQ-, and
      gender-matched controls. Comparison of variability between the ASD and neuro
      typical groups indicated that intra-participant variability of P1 latency and P1
      amplitude was greater in the participants with ASD, and inter-trial alpha-band
      phase coherence was lower in the participants with ASD. These data support the
      suggestion that individuals with ASD are less able to synchronize the activity of
      stimulus-related cell assemblies than neuro-typical individuals, and provide
      empirical evidence in support of theories of increased neural noise in ASD.

PMID- 21716922
TI  - Uncovering Multisensory Processing through Non-Invasive Brain Stimulation.
AB  - Most of current knowledge about the mechanisms of multisensory integration of
      environmental stimuli by the human brain derives from neuroimaging experiments.
      However, neuroimaging studies do not always provide conclusive evidence about the
      causal role of a given area for multisensory interactions, since these techniques
      can mainly derive correlations between brain activations and behavior.
      Conversely, techniques of non-invasive brain stimulation (NIBS) represent a
      unique and powerful approach to inform models of causal relations between
      specific brain regions and individual cognitive and perceptual functions.
      Although NIBS has been widely used in cognitive neuroscience, its use in the
      study of multisensory processing in the human brain appears a quite novel field
      of research. In this paper, we review and discuss recent studies that have used
      two techniques of NIBS, namely transcranial magnetic stimulation and transcranial
      direct current stimulation, for investigating the causal involvement of
      unisensory and heteromodal cortical areas in multisensory processing, the effects
      of multisensory cues on cortical excitability in unisensory areas, and the
      putative functional connections among different cortical areas subserving
      multisensory interactions. The emerging view is that NIBS is an essential tool
      available to neuroscientists seeking for causal relationships between a given
      area or network and multisensory processes. With its already large and fast
      increasing usage, future work using NIBS in isolation, as well as in conjunction
      with different neuroimaging techniques, could substantially improve our
      understanding of multisensory processing in the human brain.

PMID- 21716923
TI  - Hepatoprotective effect of feeding celery leaves mixed with chicory leaves and
      barley grains to hypercholesterolemic rats.
AB  - Celery, chicory leaves, and barley grains are valuable in weight loss diets and
      regulate lipid metabolism. They may reduce risk of fatty liver. The present study
      aimed to investigate the effect of diet supplementation with celery, chicory, and
      barley powder on liver enzymes and blood lipids in rats fed with cholesterol
      enriched diet. This study used four groups of rats fed with 3% cholesterol were
      supplemented diet to induce hypercholesterolemia and one group was fed on
      cholesterol-free basal diet. The dry powder of celery leaves, chicory leaves, and
      barley grains was separately added to the basal diet at 10% concentration or in
      combination of three plants at 15% for four weeks. Biochemical analyses of serum
      liver enzymes and blood lipids as well as histopathological examination of liver
      were performed. Feeding of diet supplemented with 10% of celery, 10% chicory, and
      10% of barley lowered the elevated serum level of liver enzymes and blood lipids
      in rats. Feeding plant combination of celery, chicory, and barley at 15%
      concentration (5% from each) was more effective in decreasing the elevation of
      liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline
      phosphatase) and blood lipids. The histopathological lesions seen in the livers
      of hypercholesterolemic rats were ameliorated by feeding this plant mixture. This
      study recommends that dietary intake of plant mixture of celery; chicory, and
      barley at 15% (5% of each) concentration can be beneficial to patients suffering
      from hypercholesterolemia and liver diseases.

PMID- 21716924
TI  - Standardization of spray-dried powder of Piper betle hot water extract.
AB  - The leaves of Piper betle Linn. (Family: Piperaceae) possess several
      bioactivities and are used in the Traditional Medical systems of Sri Lanka. The
      present investigation was carried out to standardize the spray-dried powder of P.
      betle by (a) determination of physicochemical parameters, presence or absence of
      heavy metals, and microbial contamination; (b) screening for phytochemicals; and
      (c) development of High Pressure Liquid Chromatography (HPLC) fingerprint and
      densitogram. The percentages of moisture content, total ash, acid insoluble ash,
      water-soluble ash, and ethanol extractable matter of spray-dried powder of P.
      betle were 2.2-2.5, 6.8-7.0, 0.003-0.005, 4.1-4.3, and 15.8-16.2, respectively.
      The concentrations of all the tested heavy metals were below the WHO acceptable
      limits and bacterial species, such as Escherichia coli, Salmonella spp,
      Staphylococcus aureus, and Pseudomonas aeroginosa were not present in the P.
      betle spray-dried powder. Phenolic compounds, tannins, flavonoids steroids, and
      alkaloids were found to be present in the spray-dried powder of P. betle and HPLC
      fingerprint and densitogram clearly demonstrated the proportional differences of
      these chemical constituents. In conclusion, the results obtained from this study
      can be used to standardize the spray-dried powder of P. betle.

PMID- 21716925
TI  - Total phenolic distribution of juice, peel, and seed extracts of four pomegranate
      cultivars.
AB  - The total phenolic distribution of juice, peel, and seed extracts of four Turkish
      pomegranate, Punica granatum L., cultivars ("Lefan," "Katirbasi," "Cekirdeksiz
      IV," and "Asinar") was investigated. Total phenolic compounds were determined
      with the Folin-Ciocalteu colorimetric method. The results showed that the levels
      of total phenolic compounds changed depending on cultivars and fruit parts. In
      all cultivars, the highest levels of total phenolic content were obtained from
      the peel extracts. The total phenolic content ranged from 1775.4 to 3547.8 mg
      gallic acid equivalent (GAE)/L among the cultivars. However, the total phenolic
      content of pomegranate juice and seed extract ranged from 784.4 to 1551.5 mg
      GAE/L and 117.0 to 177.4 mg GAE/L, respectively. "Lefan" displayed the highest
      amount of the total phenolic content among the four popular cultivars tested.

PMID- 21716926
TI  - Phytochemical screening, antioxidant, and antimicrobial activities of the crude
      leaves' extract from Ipomoea batatas (L.) Lam.
AB  - BACKGROUND: Ipomoea batatas (L.) Lam., popularly known as sweet potato (SP), has
      played an important role as an energy and a phytochemical source in human
      nutrition and animal feeding. Ethnopharmacological data show that SP leaves have
      been effectively used in herbal medicine to treat inflammatory and/or infectious
      oral diseases in Brazil. The aim of this research was to evaluate the
      phytochemical, antioxidant, and antimicrobial activities of the crude leaves'
      extract of SP leaves. MATERIALS AND METHODS: The screening was performed for
      triterpenes/steroids, alkaloids, anthraquinones, coumarins, flavonoids, saponins,
      tannins, and phenolic acids. The color intensity or the precipitate formation was
      used as analytical responses to these tests. The total antioxidant capacity was
      evaluated by the phosphomolybdenum complex method. Antimicrobial activity was
      made by agar disk and agar well diffusion tests. RESULTS: The phytochemical
      screening showed positive results for triterpenes/steroids, alkaloids,
      anthraquinones, coumarins, flavonoids, saponins, tannins, and phenolic acids.
      Total contents of 345.65, 328.44, and 662.02 mg were respectively obtained for
      alkaloids, anthraquinones, and phenolic compounds in 100 g of the dry sample. The
      total antioxidant capacity was 42.94% as compared to ascorbic acid. For
      antimicrobial studies, no concentration of the SP freeze dried extract was able
      to inhibit the growth of Streptococcus mutans, S. mitis, Staphylococcus aureus,
      and Candida albicans in both agar disk and agar well diffusion tests.
      CONCLUSIONS: SP leaves demonstrated the presence of secondary metabolites with
      potential biological activities. No antimicrobial activity was observed.

PMID- 21716927
TI  - Evaluation of cytotoxicity and genotoxicity of some Philippine medicinal plants.
AB  - The genotoxicity and toxicity of ethnomedicinal Philippine plants, which include
      Cassia fistula, Derris elliptica, Ficus elastica, Gliciridia sepium, Michelia
      alba, Morus alba, Pogostemon cablin and Ricinus communis, were tested using the
      Vitotox assay. The plants are used traditionally to treat several disorders like
      diabetes, weakness, menorrhagia, headache, toothache and rheumatism. The dried
      leaves were homogenized for overnight soaking in methanol at room temperature.
      The resulting alcoholic extracts were filtered and concentrated in vacuo and
      tested for their genotoxicity and cytotoxicity using Vitotox(r). Results showed
      that the medicinal plants that were tested are not genotoxic nor cytotoxic,
      except for R. communis and P. cablin, which showed toxicity at high doses (low
      dilutions) in the absence of S9.

PMID- 21716928
TI  - Citing Phcog Mag. articles made easy.

PMID- 21716929
TI  - Simultaneous determination of secondary metabolites from Vinca rosea plant
      extractives by reverse phase high performance liquid chromatography.
AB  - BACKGROUND: Vinca rosea (Apocynaceae) is one of the most important and high value
      medicinal plants known for its anticancer alkaloids. It is the iota of the
      isolated secondary metabolites used in chemotherapy to treat diverse cancers.
      Several high performance liquid chromatography (HPLC) methods have been developed
      to quantify the active alkaloids in the plant. However, this method may serve the
      purpose in quantification of V. rosea plant extracts in totality. OBJECTIVE: To
      develop and validate the reverse phase (RP)-HPLC method for simultaneous
      determination of secondary metabolites, namely alkaloids from V. rosea plant
      extracts. MATERIALS AND METHODS: The quantitative determination was conducted by
      RP-HPLC equipped with ultraviolet detector. Optimal separation was achieved by
      isocratic elution with mobile phase consisting of methanol:acetonitrile:ammonium
      acetate buffer (25 mM) with 0.1% triethylamine (15:45:40 v/v) on a column (Zorbax
      Eclipse plus C(18), 250 mm % 4.6 mm; 5 MUm). The standard markers (vindoline,
      vincristine, catharanthine, and vinblastine) were identified by retention time
      and co-injected with reference standard and quantified by external standard
      method at 297 nm. RESULTS: The precision of the method was confirmed by the
      relative standard deviation (R.S.D.), which was lower than 2.68%. The recoveries
      were in the range of 98.09%-108%. The limits of detection (LOD) for each marker
      alkaloids were lower than 0.20 MUg. Different parts of the V. rosea extracts
      shows different concentrations of markers, flower samples were high in
      vinblastine content, while methanol extract from the leaves contains all the four
      alkaloids in good yield, and there is no significant presence of markers in water
      extracts. CONCLUSION: HPLC method established is appropriate for the
      standardization and quality assurance of V. rosea plant extracts.

PMID- 21716930
TI  - Sterols from the red algae, Gracilaria salicornia and Hypnea flagelliformis, from
      Persian Gulf.
AB  - CONTEXT: Two of the important algae from Persian Gulf are Gracilaria salicornia
      and Hypnea flageliformis (Rhodophyta). Antibacterial, antifungal, and cytotoxic
      effects of the mentioned algae have been presented in the previous studies. AIM:
      In this study, the isolation and structural elucidation of the sterols from these
      algae are reported. MATERIALS AND METHODS: The separation and purification of the
      compounds were carried out with silica gel, sephadex LH(20) column chromatography
      (CC) and HPLC to obtain six pure compounds 1-6. The structural elucidation of the
      constituents was based on the data obtained from H-NMR,(13)C-NMR, HMBC, HSQC,
      DEPT, and EI-MS. RESULTS: The isolated compounds from G. salicornia were
      identified as 22-dehydrocholesterol (1), cholesterol (2), oleic acid (3), and
      stigmasterol (4), and the isolated constituents from H. flagelliformis were
      identified as 22-dehydrocholesterol (1), cholesterol (2), oleic acid (3),
      cholesterol oleate (5), and (22E)-cholesta-5,22-dien-3beta-ol-7-one (6) based on
      the spectral data compared to those reported in the literature. CONCLUSION: Red
      algae are enriched with cholesterol polysaccharides. We first reported the
      presence of cholesteryl oleate and (22E)-cholesta-5,22-dien-3beta-ol-7-one in H.
      flagelliformis.

PMID- 21716931
TI  - Male infertility clinic - Is it useful?

PMID- 21716932
TI  - Comparison of three different endoscopic techniques in management of bladder
      calculi.
AB  - INTRODUCTION: We present our experience of comparison of endoscopic treatment of
      vesical calculus in bladder stone. MATERIALS AND METHODS: This study included 67
      patients of bladder stone treated in this hospital from between June 2006 to
      December 2009 who were randomly assigned in three groups-group 1 (transurethral
      removal using a nephroscope), group 2 (transurethral removal using a cystoscope),
      and group 3 (percutaneous removal using a nephroscope). RESULTS: Statistical
      significant difference was observed in operating time-group 1 (32.1+ 8.5 mins),
      group 2 (69.2 +16.3), and group 3 (46 + 7.3). Statistically significant
      difference was also observed in the postoperative stay of the patient, which was
      highest for the group 3 patients. Complete clearance was achieved in all the
      patients. Group 1 had maximum number of urethral entries as compared to other two
      groups in consideration. CONCLUSIONS: Transurethral stone removal using a
      nephroscope is safe and efficacious method of stone removal without increasing
      the morbidity of the patients.

PMID- 21716933
TI  - Surgical sperm retrieval: Techniques and their indications.
AB  - Men with azoospermia can father a child through intra-cytoplasmic sperm injection
      if sperm can be retrieved from their epididymis or testis. Several percutaneous
      and open surgical procedures have been described to retrieve sperm. The various
      techniques and their merits are discussed in this review. In men with obstructive
      azoospermia, epididymal sperm can usually be retrieved by percutaneous epididymal
      sperm aspiration (PESA). If PESA fails then testicular sperm are obtained by
      needle aspiration biopsy (NAB). In men with non-obstructive azoospermia, there
      will be no sperm in the epididymis and testicular sperm retrieval is required.
      Percutaneous retrieval by NAB can be tried first. If that fails then testicular
      sperm extraction (TESE) from open microsurgical biopsies is performed using the
      single seminiferous tubule (SST) or the microdissection TESE techniques. The
      simplest, least invasive procedure should be tried first.

PMID- 21716934
TI  - Genetic and epigenetic factors: Role in male infertility.
AB  - Genetic factors contribute upto 15%-30% cases of male infertility. Formation of
      spermatozoa occurs in a sequential manner with mitotic, meiotic, and postmeiotic
      differentiation phases each of which is controlled by an intricate genetic
      program. Genes control a variety of physiologic processes, such as hypothalamus
      pituitary-gonadal axis, germ cell development, and differentiation. In the era of
      assisted reproduction technology, it is important to understand the genetic basis
      of infertility to provide maximum adapted therapeutics and counseling to the
      couple.

PMID- 21716935
TI  - In vitro fertilization/intracytoplasmic sperm injection for male infertility.
AB  - Progress in the field of assisted reproduction, and particularly
      micromanipulation, now heralds a new era in the management of severe male factor
      infertility, not amenable to medical or surgical correction. By overcoming
      natural barriers to conception, in vitro fertilization and embryo transfer (IVF
      ET), subzonal sperm insemination, partial zona dissection, and intracytoplasmatic
      injection of sperm (ICSI) now offer couples considered irreversibly infertile,
      the option of parenting a genetically related child. However, unlike IVF, which
      necessitates an optimal sperm number and function to successfully complete the
      sequence of events leading to fertilization, micromanipulation techniques, such
      as ICSI, involving the direct injection of a spermatozoon into the oocyte,
      obviate all these requirements and may be used to alleviate severe male factor
      infertility due to the lack of sperm in the ejaculate due to severely impaired
      spermatogenesis (non-obstructive azoospermia) or non-reconstructable reproductive
      tract obstruction (obstructive azoospermia). ICSI may be performed with fresh or
      cryopreserved ejaculate sperm where available, microsurgically extracted
      epididymal or testicular sperm with satisfactory fertilization, clinical
      pregnancy, and ongoing pregnancy rates. However, despite a lack of consensus
      regarding the genetic implications of ICSI or the application and efficacy of
      preimplantation genetic diagnosis prior to assisted reproductive technology
      (ART), the widespread use of ICSI, increasing evidence of the involvement of
      genetic factors in male infertility and the potential risk of transmission of
      genetic disorders to the offspring, generate major concerns with regard to the
      safety of the technique, necessitating a thorough genetic evaluation of the
      couple, classification of infertility and adequate counseling of the implications
      and associated risks prior to embarking on the procedure. The objective of this
      review is to highlight the indications, advantages, limitations, outcomes,
      implications and safety of using IVF/ICSI for male factor infertility to enable a
      more judicious use of these techniques and maximize their potential benefits
      while minimizing foreseen complications.

PMID- 21716936
TI  - Acute renal replacement therapy in children with diarrhea-associated hemolytic
      uremic syndrome: a single center 16 years of experience.
AB  - Acute kidney injury (AKI) is becoming more prevalent among hospitalized children,
      its etiologies are shifting, and new treatment modalities are evolving; however,
      diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common
      primary disease causing AKI in young children. Little has been published about
      acute renal replacement therapy (ARRT) and its challenges in this population. We
      describe our single center's experience managing 134 pediatric patients with
      D+HUS out of whom 58 (43%) required ARRT over the past 16 years. In our cohort,
      all but one patient were started on peritoneal dialysis (PD). Most patients, 47
      (81%), received acute PD on a pediatric inpatient ward. The most common recorded
      complications in our cohort were peritoneal fluid leaks 13 (22%), peritonitis 11
      (20%), and catheter malfunction 5 (9%). Nine patients (16%) needed surgical
      revision of their PD catheters. There were no bleeding events related to PD
      despite a mean platelets count of 40.9 (+/-23.5) * 10(3)/mm(3) and rare use of
      platelets infusions. Despite its methodological limitations, this paper adds to
      the limited body of evidence supporting the use of acute PD as the primary ARRT
      modality in children with D+HUS.

PMID- 21716938
TI  - Cutaneous drug hypersensitivity: immunological and genetic perspective.
AB  - Drug hypersensitivity is an unpredictable, immunologically mediated adverse
      reaction, clustered in a genetically predisposed individual. The role of "hapten
      concept" in immune sensitization has recently been contested by the
      "pharmacological interaction" hypothesis. After completion of the "human genome
      project" and with the availability of high-resolution genotyping, genetic
      susceptibility to hypersensitivity for certain drugs has been proved beyond doubt
      though the trend is ethnicity and phenotype dependent. Application of this newly
      acquired knowledge may reduce or abolish the morbidity and mortality associated
      with cutaneous drug hypersensitivity.

PMID- 21716939
TI  - Angiosarcoma of the trunk of unusual presentation in an immuno-competent man.

PMID- 21716940
TI  - Mutilating congenital erythropoeitic porphyria with blindness in a farmer.

PMID- 21716941
TI  - Subcutaneous granulomatous infection caused by phaeoacremonium infalitipes on
      foot.

PMID- 21716942
TI  - Painful bruising syndrome presenting as bullous lesions.

PMID- 21716943
TI  - Hirsutism: evaluation and treatment: a reader's dilemma.

PMID- 21716944
TI  - Author'S reply.

PMID- 21716945
TI  - Diagnosing necrolytic acral erythema: does anything go?

PMID- 21716946
TI  - Authors' reply.

PMID- 21716948
TI  - The role of laryngopharyngeal reflux as a risk factor in laryngeal cancer: a
      preliminary report.
AB  - OBJECTIVES: To evaluate the significance of laryngopharyngeal reflux (LPR) as a
      risk factor in laryngeal cancer. METHODS: We performed a case-control study with
      29 consecutive laryngeal cancer patients who had undergone 24-hour ambulatory
      double pH monitoring from 2003 to 2006. The control group included 300 patients
      who had undergone 24-hour ambulatory double pH monitoring due to LPR-related
      symptoms. We analyzed the prevalence of LPR and numerous parameters from the 24
      hour ambulatory double pH monitoring in the laryngeal cancer patient and control
      groups. Pathologic LPR is defined when more than three episodes of LPR occur in
      24 hours. RESULTS: The prevalence of pathologic LPR was significantly higher in
      the laryngeal cancer group than the control group (P=0.049). The reflux number of
      the upper probe was significantly higher in the laryngeal cancer group (P<0.001).
      However the effects of pathologic LPR on laryngeal cancer risk were diluted after
      adjusting for smoking and alcohol consumption in the multivariable logistic
      regression. CONCLUSION: The pathologic LPR might be a possible risk factor in the
      development of laryngeal cancer. A further study should be necessary to verify
      the exact role of LPR in laryngeal cancer.

PMID- 21716947
TI  - The inflammasomes: molecular effectors of host resistance against bacterial,
      viral, parasitic, and fungal infections.
AB  - The inflammasomes are large multi-protein complexes scaffolded by cytosolic
      pattern recognition receptors (PRRs) that form an important part of the innate
      immune system. They are activated following the recognition of microbial
      associated molecular patterns or host-derived danger signals (danger-associated
      molecular patterns) by PRRs. This recognition results in the recruitment and
      activation of the pro-inflammatory protease caspase-1, which cleaves its
      preferred substrates pro-interleukin-1beta (IL-1beta) and pro-IL-18 into their
      mature biologically active cytokine forms. Through processing of a number of
      other cellular substrates, caspase-1 is also required for the release of
      "alarmins" and the induction and execution of an inflammatory form of cell death
      termed pyroptosis. A growing spectrum of inflammasomes have been identified in
      the host defense against a variety of pathogens. Reciprocally, pathogens have
      evolved effector strategies to antagonize the inflammasome pathway. In this
      review we discuss recent developments in the understanding of inflammasome
      mediated recognition of bacterial, viral, parasitic, and fungal infections and
      the beneficial or detrimental effects of inflammasome signaling in host
      resistance.

PMID- 21716949
TI  - Post-intubation tracheoesophageal fistula with posterior glottic web.
AB  - Tracheoesophageal fistula (TEF) after prolonged intubation could present as
      chronic aspiration and could be mistaken as unilateral or bilateral vocal fold
      palsy, especially when there was combined posterior glottic synechia. We present
      a case of post-intubation TEF which was successfully treated with tracheal
      resection and anastomosis with primary esophageal closure. The accompanying
      posterior glottic web was treated by endoscopic technique of web lysis, with
      topical application of mitomycin C solution.

PMID- 21716950
TI  - Cavernous hemangioma of the tympanic membrane.
AB  - Cavernous hemangioma seems to most frequently arise in the posterior portion of
      the external auditory canal. However, they rarely occur in the tympanic membrane.
      A 49-year-old male patient was referred for evaluation of right-sided pulsatile
      tinnitus that he'd experienced for the previous 2 years. Temporal bone
      computerized tomography showed an isolated soft tissue mass just lateral to the
      tympanic membrane. There was no evidence of bony erosion or middle ear invasion.
      The patient underwent excision of the mass using a postauricular approach. The
      mass was removed en bloc and the defect of the tympanic membrane was repaired by
      tympanoplasty type I. There was no recurrence after 1 year of follow-up.

PMID- 21716951
TI  - Fundamental principles in aesthetic rhinoplasty.
AB  - This review article will highlight several fundamental principles and advances in
      rhinoplasty. Nasal analysis has become more sophisticated and thorough in terms
      of breaking down the anomaly and identifying the anatomic etiology. Performing
      this analysis in a systematic manner each time helps refine these skills and is a
      prerequisite to sound surgical planning. Dorsal augmentation with alloplastic
      materials continue to be used but more conservatively and often mixed with
      autogenous grafts. Long term outcomes have also taught us much with regards to
      wound healing and soft tissue contracture. This is best demonstrated with a hump
      reduction where the progressive pinching at the middle vault creates both
      aesthetic and functional problems. Correcting the twisted nose is challenging and
      requires a more aggressive intervention than previously thought. Both cartilage
      and soft tissue appear to have a degree of memory that predispose to recurrent
      deviations. A complete structural breakdown and destabilization may be warranted
      before the nose is realigned. This must be followed by careful and meticulous
      restabilization. Tip refinement is a common request but no single maneuver can be
      universally applied; multiple techniques and grafts must be within the surgeon's
      armamentarium.

PMID- 21716952
TI  - Expression of EGFR and Microvessel Density in Middle Ear Cholesteatoma.
AB  - OBJECTIVES: Cholesteatoma destructs bony tissue by the interactions between
      hyperproliferative epithelial cells and subepithelial inflammatory cells. The aim
      of this study was to evaluate the expression of epidermal growth factor receptor
      (EGFR) and microvessel density (MVD) in middle ear cholesteatoma tissue in an
      effort to determine the relationship between expression of EGFR and
      neovascularization. METHODS: We evaluated the expression of EGFR and MVD by
      immunohistochemical staining for CD31 and Factor VIII in 32 cholesteatoma tissue
      samples and 7 normal postauricular skin samples. We also analyzed the correlation
      between EGFR expression and MVD. RESULTS: The expression of EGFR was higher in
      cholesteatoma than in postauricular skin, but the difference was not
      statistically significant. EGFR was more highly expressed in the suprabasal layer
      than in the basal layer. Using CD31 and Factor VIII, we analyzed the MVD and
      found that it was significantly higher in cholesteatoma than in postauricular
      skin, and significantly correlated with the expression of EGFR. CONCLUSION: Our
      results suggest that overexpression of EGFR and neovascularization are correlated
      with the growth of cholesteatoma.

PMID- 21716953
TI  - Is cognitive function in adults with hearing impairment improved by the use of
      hearing AIDS?
AB  - OBJECTIVES: In the present study, we investigated whether speech-related
      cognitive function and speech recognition ability under background noise in
      adults with hearing impairment are improved with the use of hearing aids.
      METHODS: Participants were recruited from the ENT Department of Eulji Hospital
      from September 2008 to July 2009. The study group comprised 18 participants (mean
      age, 69.5+/-8.3 years) with sensorineural hearing loss who were fitted with
      hearing aids, and the control group comprised 11 participants of equivalent age
      (mean age, 63.1+/-11.8 years) who were not fitted with hearing aids. All
      participants were assessed using the computerized Korean visual verbal learning
      test (VVLT) and words-in-noise (WIN) test prior to fitting of hearing aids for
      the study group and initially for the control group. Both groups were reassessed
      in both tests after 6 months. For each group, differences in the results between
      the two assessments were compared using the Friedman test. RESULTS: There was no
      difference in mean age between the study group and control group. In the study
      group, total VVLT score (reflecting short-term memory) was significantly improved
      from before hearing aid use to 6 months after hearing aid use (P<0.05), and VVLT
      recognition score (reflecting learning ability) was also significantly improved
      from before hearing aid use to 6 months after hearing aid use (P<0.05), but there
      was no change in the control group. For VVLT latency score (reflecting efficiency
      of memory) and speech discrimination score in the WIN test, no statistically
      significant difference was found between the initial and 6-month assessments in
      the study group or in the control group (P>0.05). CONCLUSION: The speech-related
      cognitive function of individuals with hearing impairment improved after using
      hearing aids. This finding indicates that hearing aids may induce acclimatization
      of the central auditory system.

PMID- 21716954
TI  - Protective Effect of Minocycline Against Cisplatin-induced Ototoxicity.
AB  - OBJECTIVES: Cisplatin, a widely used chemotherapeutic agent, has serious side
      effects, including nephrotoxicity and ototoxicity. Minocycline is a semisynthetic
      second-generation tetracycline that exerts anti-inflammatory and neuroprotective
      effects. The purpose of this study was to elucidate the protective effect of
      minocycline against cisplatin-induced ototoxicity in the auditory hair cell.
      METHODS: The House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line and guinea
      pigs were used for in vitro and in vivo experiments. Cells were exposed to
      cisplatin with or without pre-treatment with minocycline. Cell survival was
      analyzed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide). Whole-cell lysates were collected and immunoblotted with antibodies
      against Bcl-2, p-c-Jun, active caspase-3, cleaved poly (ADP-ribose) polymerase
      (PARP), and apoptosis-inducing factor (AIF). The guinea pigs received
      intraperitoneal injections of cisplatin alone or following minocycline
      pretreatment. The auditory brainstem response was tested and the cochleae were
      harvested and evaluated using scanning electron microscopy. RESULTS: Survival
      significantly increased in cells pretreated with minocycline compared with cells
      exposed to cisplatin alone. Cisplatin treatment increased the expression of
      active caspase 3, p-c Jun, PARP, and AIF, and pretreatment with minocycline
      attenuated this response. In animal study, the threshold shift by cisplatin
      injection in the auditory brainstem response was less pronounced in animals
      pretreated with minocycline. Scanning electron microscopy revealed more severe
      damage to the outer hair cells at the basal and middle turns than the apical
      turn. CONCLUSION: Minocycline partially protects against cisplatin-induced
      ototoxicity via both caspase-dependent and independent apoptosis pathways.

PMID- 21716955
TI  - A Randomized, Double-blinded, Open Label Study of the Efficacy and Safety of
      Cefcapene Pivoxil and Amoxicillin.Clavulanate in Acute Presumed Bacterial
      Rhinosinusitis.
AB  - OBJECTIVES: Currently established first line therapy of acute (presumed
      bacterial) rhinosinusitis (ARS) consists of 10 to 14 days of oral amoxicillin or
      cephalosporins. This study compared the clinical efficacy and tolerance of
      cefcapene pivoxil (CP) and amoxicillin-clavulanate (AMC) in patients with ARS.
      METHODS: A randomized, open labeled, double-blinded trial of ARS patients over 15
      years of age was performed. Patients diagnosed with ARS received paranasal sinus
      X-rays and nasal endoscopies and 2 weeks of either CP (150 mg, 3 times/ day) or
      AMC (625 mg, amoxicillin 500 mg, 3 times/day). All patients revisited the clinic
      on days 7, 14, and 28 for evaluation of changes in symptoms, endoscopy, and
      monitoring of any adverse reactions. Demographics, clinical characteristics and
      drug efficacy were also compared between the two groups. RESULTS: Among the 60
      initially enrolled patients (CP 30, AMC 30), 5 patients in the CP group and 6 in
      the AMC group were excluded due to poor compliance. There were no significant
      differences in demographic data including age, sex, initial signs and symptoms,
      endoscopic and X-ray findings between the two groups. Rates of improvement after
      2 weeks were 96% and 95.8% in the CP and AMC group, respectively. Sinus symptoms
      were changed significantly after 2 and 4 weeks, however, there was no difference
      between groups (P=0.41). The most common adverse reaction was gastrointestinal
      complication, diarrhea occurred in 1 patient in the CP group and 6 in the AMC
      group (P=0.04). CONCLUSION: CP and AMC were both effective in treating ARS. The
      difference of treatment outcome was not found between the two groups, however,
      gastrointestinal complications were less prevalent in the CP group.

PMID- 21716956
TI  - Expression of matrix metalloproteinases and their inhibitors in squamous cell
      carcinoma of the tonsil and their clinical significance.
AB  - OBJECTIVES: To investigate expressions of matrix metalloproteinases (MMPs) and
      tissue inhibitors of metalloproteinases (TIMPs) in squamous cell carcinoma of the
      tonsil and to correlate expression profiles with clinicopathological
      characteristics. METHODS: Paraffin blocks were obtained from 45 tonsil squamous
      cell carcinoma (SCC) patients, who underwent surgery as an initial treatment
      between 1994 and 2004, and from 20 normal controls. Expressions of MMP-2, MMP-9,
      MMP-13, TIMP-1, and TIMP-2 were investigated immunohistochemically. RESULTS: The
      expressions of MMPs (except MMP-2) and TIMPs were found to be significantly
      different in tonsil SCC and normal control tissues. Furthermore, MMP-13
      expression was found to be correlated with tumor invasion (P=0.05), and the
      expressions of MMP-9 and TIMP-1 with nodal metastasis (P=0.048, 0.031). No
      relation was found between MMP or TIMP expression and recurrence. However, MMP-9
      expression was found to be significantly associated with 5-year survival in
      tonsil SCC patients by multivariate analysis (hazard ratio, 3.853; P=0.013).
      CONCLUSION: Significant overexpressions of multiple MMPs and TIMPs were found in
      tonsil SCC tissues. Furthermore, our findings suggest that MMP-9 expression might
      be a useful prognostic factor.

PMID- 21716957
TI  - Reliable early prediction for different types of post-thyroidectomy hypocalcemia.
AB  - OBJECTIVES: High incidence of hypocalcemia after thyroidectomy is a major
      determinant in delay of discharge. Even though many studies have focused on the
      search for reliable early predictors of postoperative hypocalcemia, definitions
      of hypocalcemia are diverse; therefore, interpretation and application of
      previously reported findings may not be easy. We aimed to elucidate diverse
      patterns of post-thyroidectomy hypocalcemia and to provide reliable early
      predictors for these different types of hypocalcemia. METHODS: Retrospective
      chart review was performed and eligible 112 patients of thyroidectomy were
      categorized into four groups according to symptomatic and/or biochemical
      hypocalcemic criteria. A mismatch of occurrence and the timing of symptomatic or
      biochemical abnormalities were evaluated. Predictive values of commonly used
      biomarkers were compared in each group; levels of serum total calcium and ionized
      calcium, and intact parathyroid hormone (PTH). RESULTS: Among 62 hypocalcemic
      patients, 45 patients (72.5%) experienced both symptomatic and biochemical
      abnormalities during hospitalization. A mismatch on the timing of initial
      detection of symptomatic and biochemical hypocalcemia was observed in 21 patients
      (46.6%). Intact PTH level measured at 1 hour was a useful indicator in prediction
      of symptomatic hypocalcemia with 79.7-87.4% of diagnostic accuracy. Serum ionized
      calcium measured next morning after surgery was a reliable predictor of
      biochemical hypocalcemia with 77.9-94.8% of diagnostic accuracy. CONCLUSION: For
      the safety of patients, the possibility of both symptomatic and biochemical
      hypocalcemia should be considered together before deciding early discharge. Using
      intact PTH for symptomatic hypocalcemia and day-1 ionized serum calcium level for
      biochemical hypocalcemia will be helpful for the reliable prediction of
      heterogeneous nature of postoperative hypocalcemia.

PMID- 21716958
TI  - The Differential Effect of Toxoplasma Gondii Infection on the Stability of BCL2
      Family Members Involves Multiple Activities.
AB  - The regulation of mitochondrial permeability, a key event in the initiation of
      apoptosis is governed by the opposing actions of the pro- and anti-apoptotic
      members of the BCL2-family of proteins. The BCL2-family can be classified further
      based on the number of BCL-homology (BH) domains they encode. Pathogen mediated
      modulation of BCL2-family members play a significant role in their ability to
      affect the apoptotic pathways in the infected host cell. The protozoan parasite
      Toxoplasma gondii establishes a profound blockade of apoptosis noted by a
      requirement for host NFkappaB activity and correlating with the selective
      degradation of pro-apoptotic BCL2-family members. In this study, we explore the
      potential activities associated with the inherent stability of the anti-apoptotic
      BCL2 as well as the selective degradation of the pro-apoptotic proteins BAX, BAD,
      and BID. We find that multiple activities govern the relative stability of BCL2
      family members suggesting a complex and balanced network of stability-enhancing
      and-destabilizing activities are perturbed by parasite infection. The data leave
      open the possibility for both parasite induced host activities as well as the
      direct consequence of parasite effectors in governing the relative levels of BCL2
      proteins in the course of infection.

PMID- 21716959
TI  - Train-of-Four monitoring: overestimation.

PMID- 21716960
TI  - Recent advances in pediatric anesthesia.
AB  - Writing about advances in a field of medicine normally includes some pride about
      progress which one was witness to or even a participant in. The younger one is,
      the more enthusiastically every advance is lauded and welcomed. This is human
      nature and nothing to be complained about. However, when anesthesiologists,
      having worked and struggled in the field of pediatric anesthesia for about 40
      years, look back to past advances, a more realistic, even painful picture comes
      to mind. There was a price which a considerable number of patients had to pay for
      progress, ruined health or even death. This experience of decades of practice is
      rarely presented in the literature but should not be forgotten when we proudly
      remember advances in pediatric anesthesia.

PMID- 21716961
TI  - Study for the discrepancy of arterial blood pressure in accordance with method,
      age, body part of measurement during general anesthesia using sevoflurane.
AB  - BACKGROUND: Many pieces of previous research on measuring blood pressure (BP)
      using different methods focused on the disparity in the results. However, none of
      them dealt with the disparity caused by the difference in age and inhalation
      anesthetics. We attempted to find the variance in accordance with age, body part,
      and measuring methods (invasive vs noninvasive) and also studied how sevoflurane
      influences BP as the operation progresses. METHODS: In sixty patients, we
      measured the arterial BP in the upper and lower limbs by noninvasive methods
      before inducing anesthesia. After induction, we used sevoflurane to maintain
      anesthesia, and injected catheters into the radial artery and dorsalis pedis
      artery to measure arterial pressure at every ten minute by both invasive and
      noninvasive methods. RESULTS: The patients who were 40 or older showed
      significantly higher values in the systolic BP than the patients younger than 40.
      The values of systolic and diastolic BP measured by a noninvasive oscillometric
      method were meaningfully higher than those measured by an invasive method. As the
      operations progressed, the lower limbs showed higher systolic pressure than the
      upper limbs regardless of measuring methods, whereas the opposite is true for
      diastolic pressure. CONCLUSIONS: The values in the arterial BP were measured high
      by noninvasive method. Systolic BP were estimated significantly high in the older
      patients and in the lower leg. Due to the effect of sevoflurane, the diastolic BP
      in the lower limbs becomes lower than that of upper limbs regardless of measuring
      methods, as the operation progresses.

PMID- 21716962
TI  - Evaluation of dose effects of magnesium sulfate on rocuronium injection pain and
      hemodynamic changes by laryngoscopy and endotracheal intubation.
AB  - BACKGROUND: Rocuronium produces injection pain in 50-80% of treated patients.
      Therefore, a variety of pretreatments have been attempted to reduce this issue.
      We evaluated the efficacy of 3 different doses of magnesium on the rocuronium
      injection pain and following hemodynamic changes by laryngoscopy and tracheal
      intubation (LTI). METHODS: Two hundreds patients, ASA I and II, undergoing
      general anesthesia for elective surgery were randomly divided to 4 groups: group
      1, 2, 3, 4 received saline 5 ml, magnesium 5, 10 and 20 mg/kg prior to 0.6 mg/kg
      of rocuronium, respectively. Then, group 1 only was treated with esmolol (20 mg)
      before LTI. Pain intensity with rocuronium injection was assessed using a four
      point scale according to patient's movement. Cardiovascular responses at
      baseline, after induction, 1 minutes after LTI were determined. RESULTS: Compared
      to saline, 10 and 20 mg/kg of magnesium significantly reduced the incidence of
      overall movement after rocuronium injection (34% and 36% in group 3 and 4,
      respectively vs. 76% in the group 1) (P < 0.0001). Generalized movement was seen
      in 4% of patients in groups 3 and 4, respectively. Compared to baseline values,
      diastolic blood pressure (DBP) immediately after LTI significantly increased
      within groups 1 and 2 (P < 0.001), but not within groups 3 and 4. CONCLUSIONS:
      Magnesium (10 and 20 mg/kg) prior to rocuronium was effective in attenuating
      rocuronium associated injection pain and cardiovascular changes by LTI.

PMID- 21716963
TI  - A comparison of the accuracy of ulnar versus median nerve stimulation for
      neuromuscular monitoring.
AB  - BACKGROUND: Inexperienced anesthesiologists are frequently unclear as to whether
      to stimulate the ulnar or median nerve to monitor the adductor pollicis. The
      primary purpose of this study was to determine whether monitoring the adductor
      pollicis by positioning the stimulating electrodes over the median nerve is an
      acceptable alternative to applying electrodes over the ulnar nerve. METHODS: In
      20 patients anesthetized with propofol and remifentanil, one pair of stimulating
      electrodes was positioned over the ulnar nerve. A second pair was placed over the
      median nerve on the other hand. The acceleromyographic response was monitored on
      both hands. Rocuronium 0.6 mg/kg was administered. Single twitch (ST) and train
      of-four (TOF) stimulations were applied alternatively to both sites. RESULTS:
      None of the patients showed a twitch response at either site after injection of
      rocuronium. There were no differences in the mean supramaximal threshold, mean
      initial TOF ratio, or mean initial ST ratio between the two sites. Bland-Altman
      analysis revealed a bias (limit of agreement) in the TOF and ST ratios over the
      median nerve of 7% (+/- 31%) and 26% (+/- 73%), respectively, as compared with
      the ulnar nerve. The median nerve TOF ratio was overestimated by 16.2%, as
      compared with that of the ulnar nerve value, and the median nerve ST ratio was
      overestimated by 72.9%, as compared to that of the ulnar nerve. CONCLUSIONS: The
      ulnar and median nerves cannot be used interchangeably for accurate neuromuscular
      monitoring.

PMID- 21716964
TI  - [Diagnosis and pharmacological and nonpharmacological treatment of fibromyalgia.
      Compendium of the best evidence].
AB  - Chronic generalized musculoskeletal pain is one of the most common reasons for
      consultation in daily medical practice, and it poses a diagnostic and therapeutic
      challenge. Fibromyalgia is one of the so-called central sensitization syndromes,
      mainly characterized by generalized pain in the musculoskeletal system.
      Fibromyalgia diagnosis is basically clinical, and it should be considered
      whenever patients complain of generalized pain. Patients with chronic
      inflammatory diseases may also suffer from fibromyalgia, and this condition may
      be the reason for the pain they complain of in medical consultations. The aim of
      this review paper has been to provide our readers with a summary of the best
      available evidence about this disease based upon an updated review of scientific
      literature on fibromyalgia aspects, such as its diagnostic criteria,
      pathophysiology, clinical profile and differential diagnosis, followed by an
      ample systematic review of its pharmacological and non-pharmacological aspects.
      This systematic review analyses the multidisciplinary aspects in which sufficient
      evidence was found in the two strongest types of clinical research design, 1)
      controlled clinical trials and 2) systematic reviews or meta-analysis. This
      review was developed by a group of Latin American specialists from several
      countries, recognized as a group of experts in fibromyalgia study.

PMID- 21716965
TI  - Immediate versus delayed loading of dental implants in edentulous maxillae: a 36
      month prospective study.
AB  - PURPOSE: The aim of this study was to compare survival rates and radiographic
      outcomes of immediate and delayed implant loading in edentulous maxillae.
      MATERIALS AND METHODS: Forty-nine patients in need of maxillary full-arch
      treatment were randomized into two groups: test group (n = 34) treated following
      the Columbus Bridge Protocol with 4 to 6 implants loaded within 24 hours and a
      control group (n = 15) treated following the ad modum Branemark protocol with 6
      to 9 implants loaded a mean 8.75 months after surgery. Two hundred sixty implants
      (test: n = 163, control: n = 97) were placed, and subjects were treated with
      screw-retained full-arch prostheses. Bone levels were measured at baseline and at
      1, 2, and 3 years and analyzed using repeated-measures analysis of variance.
      RESULTS: All patients appeared at all scheduled recall visits. No differences in
      cumulative survival rates were found between groups at 36 months. Ten implants
      (6.1%) failed in the test group; four (4.1%) failed in the control group. At 36
      months, no prosthetic failures were detected. Significantly less bone loss was
      found in the test group at all time intervals (P < .001). The average bone level
      from the implant-abutment connection was 1.3 mm in the test group and 1.9 mm in
      the control group at 12 months, 1.5 mm and 2.2 mm at 24 months, and 1.6 mm and
      2.3 mm at 36 months, respectively. CONCLUSION: In the edentulous maxilla, the
      Columbus Bridge Protocol involving immediate loading of implants placed in both
      healed and fresh extraction sites exhibited equivalent implant survival and less
      marginal bone loss at 3 years compared to the conventional two-stage delayed
      loading protocol. Int J Prosthodont 2011;24:294-302.

PMID- 21716966
TI  - Preliminary clinical report of satisfaction with prosthodontic rehabilitation of
      intellectually disabled young adults provided by parents or caregivers.
AB  - The aim of this research was to analyze satisfaction with prosthodontic
      rehabilitation of intellectually disabled (ID) patients provided by their
      parents/caregivers. A total of 12 ID patients received fixed dentures (FDs) and
      10 patients received removable dentures (RDs). Parents/caregivers answered a
      questionnaire related to prosthodontic rehabilitation (1 = unsatisfactory, 5 =
      excellent). Parents/caregivers were mostly satisfied with their childrens' oral
      rehabilitation (results were skewed toward the highest scores). There was a
      significant improvement in masticatory function and a reduction of avoiding
      certain foods after both FD and RD therapy. RD therapy significantly improved ID
      patients' social lives. However, FD therapy increased problems with oral hygiene
      maintenance. Prosthodontic rehabilitation improves oral function of ID patients.
      Int J Prosthodont 2011;24:303-305.

PMID- 21716967
TI  - Implant-supported versus implant-retained distal extension mandibular partial
      overdentures and residual ridge resorption: a 5-year retrospective radiographic
      study in men.
AB  - PURPOSE: This retrospective study sought to examine posterior mandibular ridge
      resorption under implant-supported and implant-retained distal extension partial
      overdentures in men at the end of a 5-year observation period. MATERIALS AND
      METHODS: Class I mandibular partial edentulism was managed in 34 patients with
      removable partial overdentures that were adjunctively supported (n = 18) or
      retained (n = 16) via resilient attachments placed bilaterally on single implants
      (n = 68) in the first molar areas. Posterior Area Indices (PAI) were calculated
      for each patient by digitizing the traced rotational tomograms taken immediately
      before and after 5 years of treatment. Proportional rather than actual
      measurements were used in an effort to minimize errors related to magnification
      and distortion. RESULTS: Residual ridge resorption associated with the implant
      supported partial overdentures was recorded as PAI =0.012 +/- 0.022; it was PAI =
      0.073 +/- 0.044 for the implant-retained group. Estimated average reductions in
      ridge heights were 0.15 and 1.03 mm for implant-supported and implant-retained
      partial overdentures, respectively. Multiple linear regression models
      demonstrated that prosthesis type, initial mandibular ridge height, and relining
      frequency were significantly correlated with PAI. CONCLUSION: Implant-supported
      partial overdentures appear to be associated with reduced posterior mandibular
      alveolar ridge resorption when compared to implant-retained ones. Int J
      Prosthodont 2011;24:306-313.

PMID- 21716968
TI  - An 18-year retrospective analysis of treatment outcomes with metal-ceramic fixed
      partial dentures.
AB  - PURPOSE: The aim of this clinical retrospective study was to evaluate the
      survival and success rates of metal-ceramic fixed partial dentures (FPDs) made by
      dental students over an 18-year interval. Biologic and technical complications as
      well as patient satisfaction were recorded. MATERIALS AND METHODS: Fifty-seven
      patients with 82 FPDs from an original group of 104 patients with 128 FPDs
      attended an approximate clinical 18-year follow-up examination. The mean follow
      up period was 17.7 years (range: 17.1 to 21.3 years). RESULTS: Nine FPDs were
      lost because of extraction of an abutment tooth, and 1 FPD was removed for
      esthetic reasons. Technical problems recorded included loss of cementation,
      fractures in the metal framework, and need for placement of a dowel in an
      abutment tooth. The most common clinical findings were gingival bleeding on
      probing and appearance of supragingival crown margins. The survival rate of the
      FPDs was 78%, and the established success rate was 71%. CONCLUSION: This 18-year
      follow-up of metal-ceramic FPDs in just over half of the originally treated
      patient group was associated with good patient satisfaction and few biologic and
      technical complications. Int J Prosthodont 2011;24:314-319.

PMID- 21716969
TI  - Female hormonal fluctuation and masticatory function in patients with disc
      displacement-a case-control study.
AB  - PURPOSE: The aim of this case-control study was to investigate the role female
      hormone fluctuation plays in maximum occlusal force and masticatory performance
      in female subjects presenting disc displacement with reduction (DDR) and matched
      controls. MATERIALS AND METHODS: Sixty-five subjects were initially recruited;
      however, 4 of them were excluded during the study. The final sample included 14
      subjects with DDR taking oral contraceptives, 16 control subjects without DDR
      taking oral contraceptives, 14 normally cycling subjects with DDR, and 17
      normally cycling subjects without DDR. DDR was diagnosed by means of the Research
      Diagnostic Criteria for Temporomandibular Disorders axis I, and subjects without
      pain were selected. Maximum occlusal force was measured bilaterally in the molar
      region using a force transducer, and masticatory performance was analyzed using
      the artificial material comminution and sieving method. Variables were evaluated
      in four phases of three menstrual cycles, identified by ovulation testing. Data
      were submitted to the Mauchly sphericity test and PROC MIXED procedure of the SAS
      statistical program for repeated measures. Multiple comparisons were made using
      the Tukey-Kramer test (P ? .05). RESULTS: Comparisons among menstrual cycle
      phases showed no differences in occlusal force (P = .44) or masticatory
      performance (P = .09) for all volunteers. Subjects without DDR showed greater
      occlusal force (P = .01). No difference in occlusal force was found between
      subjects regardless of whether they took contraceptives (P = .15). Similarly,
      masticatory performance values did not differ among subjects with or without DDR
      (P = .09) or among those taking or not taking contraceptives (P = .29).
      CONCLUSION: Hormonal fluctuation did not influence mastication. Int J Prosthodont
      2011;24:320-327.

PMID- 21716970
TI  - Mandibular two-implant overdentures: three-year prosthodontic maintenance using
      the locator attachment system.
AB  - Limited clinical research identifies prosthodontic maintenance requirements of
      mandibular overdentures using the Locator attachment system. Sixty-five
      edentulous participants received complete maxillary dentures opposing mandibular
      two-implant overdentures with either Locator nylon (n = 21), Southern plastic (n
      = 24), or Straumann gold (n = 20) matrices. Prosthodontic maintenance was
      recorded prospectively for 3 years using defined categories. Over the 3-year
      period, a mean 3.52 +/- 4.8, 2.08 +/- 1.9, and 5.5 +/- 4.2 maintenance events
      occurred for Locator, Southern, and Straumann participants, respectively.
      Prosthodontic success rates of 90% in the Locator nylon group, 88% in the
      Southern plastic group, and 75% in the Straumann gold group were achieved. Int J
      Prosthodont 2011;24:328-331.

PMID- 21716971
TI  - Patient-evaluated dentistry: development and validation of a patient satisfaction
      questionnaire for fixed prosthodontic treatment.
AB  - PURPOSE: The aim of this study was to develop and verify the reliability and
      validity of a questionnaire to assess patient satisfaction with fixed dental
      prostheses (FDPs). MATERIALS AND METHODS: A questionnaire was developed, pilot
      tested, and modified. It assessed esthetics, masticatory function, phonetics,
      cleansibility, and cost satisfaction using a visual analog scale and whether
      patients would elect to undergo the same treatment again (yes/no). It was sent to
      patients with a known evidence-based outcome (survival) who received FDPs from
      1984 to 2005 (n = 986) in one private prosthodontic practice. Reliability and
      validity were analyzed using the Student t, Mann-Whitney U, Kruskal Wallis,
      Cronbach alpha, Spearman-Brown, Correlation matrix, Bartlett sphericity, Kaiser
      Meyer-Olkin (KMO), and factor analysis tests. Significance was set at P = .05.
      RESULTS: Five hundred patients responded (50.7%). A Cronbach alpha value of 0.8
      and split-sample Spearman-Brown value of 0.7 indicated good reliability. Step
      wise removal of items did not improve internal consistency. Discriminant
      construct validity assessment showed no item redundancy. Satisfaction of patients
      who had experienced prosthesis failure (n = 52) was significantly less than their
      counterparts (73% +/- 3% vs 83% +/- 0.6%, P = .004), ascertaining convergent
      construct validity. Factor analysis (Bartlett sphericity, P < .001; KMO = 0.84)
      identified two components (Eigenvalues ? 1.0) that explained 93.18% (varimax
      rotation) of variations. Component 1 included satisfaction with function
      (esthetics, mastication, phonetics, and cleansibility); component 2 included
      satisfaction with costs and whether patients would undergo the same treatment
      again. CONCLUSIONS: The Patient Satisfaction Questionnaire developed proved
      reliable and valid for assessing patient-evaluated outcomes of FDPs. Use of this
      questionnaire in further research is justified. Int J Prosthodont 2011;24:332
      341.

PMID- 21716972
TI  - Development of a stereophotogrammetry technique to assess facial change following
      surgery for head and neck cancer.
AB  - A stereophotogrammetry technique is described that can be used to map the face
      following surgery for head and neck cancer. It enables the effects of obturators
      on facial form to be assessed and may have a wide variety of applications. Int J
      Prosthodont 2011;24:342-344.

PMID- 21716973
TI  - Implant treatment with fixed prostheses in the edentulous maxilla. Part 1:
      implants and biologic response in two patient cohorts restored between 1986 and
      1987 and 15 years later.
AB  - PURPOSE: Implant treatment has been performed for more than 45 years, but there
      is still limited knowledge on how treatment outcomes are changing over time. The
      aim of this study was to report and compare the treatment outcomes of two patient
      cohorts from the same clinic, rehabilitated with fixed implant prostheses in the
      edentulous maxilla between 1986 and 1987 (early) and 2001 to 2004 (late).
      MATERIALS AND METHODS: The early group included 76 edentulous patients who were
      consecutively provided with 450 turned Branemark System implants; the late group
      included 109 edentulous patients provided with 360 turned and 310 TiUnite
      Branemark System implants. Both groups were followed and evaluated clinically and
      radiographically for 5 years according to similar protocols. RESULTS: Altogether,
      37 patients (20%) were lost to follow-up over 5 years; more patients were
      noncompliant in the late group (P < .05). The 5-year overall implant cumulative
      survival rates were 93.4% and 97.3% for the early and late groups, respectively.
      In the early group, significantly more turned implants failed before prosthesis
      insertion compared to the outcome of TiUnite implants in the late group (P <
      .05). Mean bone loss was comparable for the early and late groups during the 5
      years of follow-up (0.5 +/- 0.46 and 0.7 +/- 0.76 mm, respectively), but more
      patients presented at least 1 implant with more than 2 mm of bone loss during the
      follow-up period in the late group (P < .05). Mucosal hyperplasia and
      inflammation showed a trend of higher frequency at implants in the early group of
      patients (P > .05). CONCLUSION: Implant treatment was more predictable before
      loading in the late group of patients, related to the change in the implant
      surface (P < .05). On the other hand, it was observed that the prevalence of
      patients with more bone loss at at least 1 implant (> 2 mm) was higher in the
      late group (P < .05). This could possibly be attributed to a more bioactive
      implant surface and shorter healing period before implant surgery in the late
      group. Int J Prosthodont 2011;24:345-355.

PMID- 21716974
TI  - Implant treatment with fixed prostheses in the edentulous maxilla. Part 2:
      prosthetic technique and clinical maintenance in two patient cohorts restored
      between 1986 and 1987 and 15 years later.
AB  - PURPOSE: Implant treatment using osseointegrated implants has been performed for
      more than 40 years, but limited knowledge is available on how treatment outcomes
      have changed over time. The aim of this study was to report and compare the
      prosthetic treatment outcomes from two patient cohorts provided with fixed
      implant prostheses in the edentulous maxilla between 1986 and 1987 (early) and
      2001 to 2004 (late) at the same clinic. MATERIALS AND METHODS: The two groups of
      patients comprised 76 and 109 edentulous patients consecutively provided with 450
      and 670 Branemark System implants and fixed screw-retained prostheses,
      respectively. Both groups were followed for 5 years with regard to prosthetic
      treatment, clinical maintenance, and complications. RESULTS: Altogether, 37
      patients (20%) were lost to follow-up during the 5 years, and more patients were
      noncompliant in the late group (P < .05). Prosthetic treatment was performed
      using significantly less chair time in the late group (P < .05), and 22 and 68
      patients were followed for 5 years without any reported complications in the
      early and late groups, respectively (P < .05). The 5-year prosthesis cumulative
      survival rate was 97.1% in the early group and 100.0% in the late group. Patients
      in the late group presented fewer problems with diction and veneer fractures, and
      fewer patients had their prostheses temporarily removed for adjustments (P <
      .05). CONCLUSION: Prosthetic treatment and maintenance of implant-supported fixed
      prostheses improved significantly between the groups. Int J Prosthodont
      2011;24:356-362.

PMID- 21716975
TI  - An up to 3-Year Controlled Clinical Trial Comparing the Outcome of Glass Fiber
      Posts and Composite Cores with Gold Alloy-Based Posts and Cores for the
      Restoration of Endodontically Treated Teeth.
AB  - PURPOSE: This controlled clinical trial aimed to compare the 3-year outcomes of
      glass fiber posts and composite cores with gold alloy-based posts and cores for
      the restoration of endodontically treated teeth. MATERIALS AND METHODS: One
      hundred forty-four patients in need of 205 restorations on endodontically treated
      teeth were selected and followed for 7 to 37 months (mean: 21 +/- 9 months). The
      teeth were primarily stratified based on the remaining tissue available to
      restore the tooth core with or without a post. Then, randomization allocated the
      teeth to either test group 1 (prefabricated glass fiber posts), test group 2
      (custom-made glass fiber posts), or test group 3 (composite cores without posts).
      The control group consisted of gold alloy-based posts and cores. All posts/cores
      were covered with all-ceramic single crowns. Failures were either absolute, such
      as root fractures or irreparable fractures of the post/core, or relative, such as
      loss of post retention or reparable fractures of the core. Success and survival
      probability lifetime curves, corrected for clustering, were drawn for the entire
      data set. RESULTS: The recall rate at 3 years was 97.1%. Absolute failures
      consisted of two root fractures and one endodontic failure, while relative
      failures included three instances of retention loss of the post/core and one post
      fracture. Because of the low number of events, no statistical tests were
      performed. The success and survival probabilities over all groups together at 3
      years amounted to 91.7% and 97.2%, respectively. CONCLUSIONS: After being
      followed for up to 3 years, both cast gold and composite post and core systems
      performed well clinically. Longer follow-up times are needed to detect possible
      significant differences. Int J Prosthodont 2011;24:363-372.

PMID- 21716976
TI  - Comparative analysis of biofilm formation on dental implant abutments with
      respect to supra- and subgingival areas: polytetrafluoroethylene versus titanium.
AB  - The aim of the present in vivo study was to examine the effect of
      polytetrafluoroethylene (PTFE) surfaces on biofilm formation on dental implant
      abutments in comparison to titanium surfaces. Fifteen modified abutments with
      incorporated PTFE plates were inserted in 10 patients for 14 days. Scanning
      electron microscopy techniques were used to examine biofilm formation on
      different surfaces and to determine the percentage of surface coverage.
      Significantly less biofilm was detected on PTFE surfaces than on titanium
      surfaces. The results of this study reveal that PTFE surfaces reduce biofilm
      formation to a minimum on dental implant abutments. Int J Prosthodont 2011;24:373
      375.

PMID- 21716977
TI  - Combined effects of thermocycling and load-cycling on microleakage of computer
      aided design/computer-assisted manufacture molar crowns.
AB  - This study evaluated the combined effects of thermocycling and compressive load
      cycling on microleakage of computer-aided design/computer-assisted manufacture
      molar crowns. Sixteen ceramic (Vita Mark-II) and 16 composite resin (Paradigm MZ
      100) crowns were milled using the CEREC 3D system. Eight crowns of each group
      were cemented to prepared molars using Panavia F 2.0, and 8 were cemented using
      RelyX Unicem Clicker. Specimens were thermocycled for 500 cycles and subjected to
      load-cycling for 1,000,000 cycles (60 to 600 N). Specimens were then tested for
      microleakage. Data were analyzed statistically using the Tukey post hoc test. All
      composite resin crowns survived load and thermal fatigue, while 6 ceramic crowns
      developed cracks. There were no statistically significant differences among
      groups regarding microleakage scores. Paradigm MZ-100 crowns were more crack
      resistant to combined load and thermal fatigue than those composed to Vita Mark
      II. However, microleakage scores of both types of crowns were similar. Int J
      Prosthodont 2011;24:376-378.

PMID- 21716978
TI  - Marginal integrity of turkom-cera compared to other all-ceramic materials: effect
      of finish line.
AB  - The aim of this study was to evaluate the marginal adaptation of Turkom-Cera all
      ceramic crowns compared to In-Ceram and Procera AllCeram systems. The influence
      of finish line design (chamfer or shoulder) on the marginal adaptation of Turkom
      Cera all-ceramic crowns was also investigated. Thirty human premolars were
      prepared with chamfer margins and assigned to either the Turkom-Cera, In-Ceram,
      or Procera system group. In addition, 10 premolars were prepared with rounded
      shoulder finish lines and assigned to an additional Turkom-Cera group. Ceramic
      copings (0.6-mm thick) were fabricated for each group following the
      manufacturers' instructions. The copings were seated on abutments using a special
      holding device that facilitated uniform loading, and marginal adaptation was
      assessed using a stereomicroscope. Data were analyzed using analysis of variance,
      the Tukey HSD post hoc test, and an independent samples t test. There was a
      statistically significant difference regarding marginal adaptation among the
      three all-ceramic systems (P < .05). There were no significant differences in the
      mean marginal discrepancies of Turkom-Cera crowns among chamfer and shoulder
      finish line groups (P > .05). Within the limitations of this study, the marginal
      discrepancies were all within the clinically acceptable standard. Int J
      Prosthodont 2011;24:379-381.

PMID- 21716979
TI  - The spectrum of orofacial manifestations in renal osteodystrophy: diagnostic
      challenges of an uncommon presentation.
AB  - Renal osteodystrophy refers to a spectrum of bone diseases caused by pathologic
      alterations in the metabolism of calcium, phosphate, and bone in the context of
      end-stage renal disease and secondary hyperparathyroidism. Radiographic
      alterations affecting the jaw and facial skeleton are common and among the
      earliest signs of renal bone disease. Renal osteodystrophy also shares clinical,
      histologic, and radiologic similarities with several benign fibro-osseous
      conditions affecting the craniofacial region, and its recognition is critical to
      prevention, choice of therapy, and overall prognosis. The aim of this article is
      to review the craniofacial manifestations of renal osteodystrophy, describe the
      work-up of a patient with macrognathia and facial disfigurement caused by renal
      bone disease, discuss the challenges in arriving at a definitive diagnosis, and
      highlight an interdisciplinary approach to evaluation and timely diagnosis in
      overall management.

PMID- 21716980
TI  - Esthetic restoration of maxillary incisors using CAD/CAM chairside technology--a
      case report.
AB  - High-quality esthetic veneers can be produced in a single treatment session only
      by means of chairside CAD/CAM technology. With efficient therapy, the duration of
      the relatively long treatment cycle can be optimized: planning casts and a
      diagnostic wax-up are steps that simplify therapy decisions, the same as with
      veneers produced by laboratories. After production of a mock-up and preparation
      of the teeth, removable composite veneers can be prepared and gradually replaced
      by ceramic veneers. Modern, three-dimensional presentation by use of the Cerec 3D
      system facilitates construction of veneers seen in relation to the other teeth. A
      very helpful aspect is that the mock-ups can be adjusted to patients' needs
      during the complete production process. After individualization by a dental
      ceramic technician, there is no recognizable esthetic difference from veneers
      produced by a laboratory.

PMID- 21716981
TI  - Rehabilitation of an extensive anterior explantation defect--a case report.
AB  - This article illustrates the surgical and prosthetic rehabilitation of an
      extensive defect in the area of a mandibular lateral incisor following
      explantation of a dental implant. Bone and soft tissue defects existed after
      removal of the implant. Guided bone regeneration, a subepithelial connective
      tissue graft, and gradual pontic contouring were used to attempt correction of
      the defect. The missing tooth was replaced by a single-retainer, all-ceramic,
      resin-bonded fixed partial denture. The gingival contours were reestablished, but
      without complete regeneration of the interdental papillae. This article describes
      the use of several regenerative techniques in the treatment of dental defects and
      underscores the difficulty of complete correction of papilla deficiencies.

PMID- 21716982
TI  - Long-term radiologic pulp evaluation after partial pulpotomy in young permanent
      molars.
AB  - OBJECTIVE: Radiographic appearance of pulp reactions to partial pulpotomy in
      young permanent molars with deep caries may determine the efficiency of the
      procedure. The objective of this study was to determine the value of this
      procedure by analyzing the pulpal and periapical appearance of permanent molars
      after long-term follow-up periods. METHOD AND MATERIALS: Based on predetermined
      radiologic criteria, periapical radiographs of 49 young permanent molars of 31
      females and 13 males, aged 6.9 to 17.7 years (mean, 11.4 years) treated with
      partial pulpotomy were evaluated and compared to their antimeres. Follow-up time
      ranged from 7 to 154 months (mean, 49 months). RESULTS: Based on clinical and
      radiographic findings, the success rate was considered 93.9% (46 of 49 teeth).
      Three teeth had chronic pulpitis with periapical exacerbation. In 14 (30.4%) of
      the 46 teeth, normal radiographic pulp appearance was found, and in 2 (4.3%),
      pulpal calcifications were similar to their antimere tooth. Dentinal bridges were
      observed underneath the partial pulpotomy site in 27 molars (58.7%), while
      radiopacities in the pulpotomized pulp horns of 5 teeth (10.9%) suggested
      development of obstructive calcifications. Increased calcifications of the pulp
      were seen in 13 (28.3%) molars, in comparison with their antimeres. Six of the 46
      molars with immature root development completed full apexogenesis. No periapical
      pathoses, total pulp obliteration, or resorption were observed. CONCLUSION: The
      long-term radiologic interpretation of the pulp after partial pulpotomy in young
      permanent molars supports the clinical impression that it is a warranted
      treatment in well-chosen cases.

PMID- 21716983
TI  - Effect of smoking on the results of a chlorhexidine digluconate treatment
      extended up to 3 months after scaling and root planing-a pilot study.
AB  - The aim of the study was to evaluate the impact of smoking on a prolongated
      chlorhexidine digluconate regimen after scaling and root planing. Forty-two
      smokers (test group) and 85 nonsmoking patients (control group) with generalized
      chronic periodontitis were examined for clinical attachment level (CAL), probing
      depth (PD), bleeding on probing (BoP), and Plaque Index (Pl) at baseline and
      after 1 and 3 months. During scaling and root planing, a 0.2% chlorhexidine
      digluconate solution and a 1% chlorhexidine digluconate gel were used. The
      subjects used a 0.2% chlorhexidine digluconate solution twice daily for 3 months.
      The Mann-Whitney U and Wilcoxon tests were used for statistical analysis. There
      were significant improvements of all studied variables after 1 and 3 months in
      both groups. After 3 months, the mean improvement in the test group was 1.62 mm
      for CAL, 2.85 mm for PD, and 48% for BoP; in the control group, the values were
      2.18 mm for CAL, 2.81 mm for PD, and 47% for BoP. Only the maximum changes of CAL
      between 1 and 3 months (test group, 0.32 mm vs 0.69 mm in the control group) and
      PD (test group, 0.47 mm vs 0.76 mm in the control group) were significantly
      different between the groups (P < .05 and P = .05, respectively). The present
      data appear to suggest that the use of chlorhexidine digluconate twice daily
      during a period of 3 months following nonsurgical periodontal therapy may result
      in significant clinical improvements in smokers and nonsmokers.

PMID- 21716984
TI  - In vivo biofilm formation on different dental ceramics.
AB  - OBJECTIVES: To investigate the formation of oral biofilm on various dental
      ceramics in vivo. METHOD AND MATERIALS: Five different ceramic materials were
      included: a veneering glass- ceramic, a lithium disilicate glass-ceramic, a
      yttrium-stabilized zirconia (Y-TZP), a hot isostatically pressed (HIP) Y-TZP
      ceramic, and an HIP Y-TZP ceramic with 25% alumina. Test specimens were attached
      to individually designed acrylic appliances; five volunteers wore these
      appliances for 24 hours in the maxillary arch. After intraoral exposure, the
      samples were removed from the appliances and the adhering biofilms vitally
      stained. Then, the two-dimensional surface coating and thickness of the adhering
      biofilm were determined by confocal laser scanning microscopy. Statistical
      analysis was performed using one-way ANOVA with the level of significance set at
      .05. RESULTS: Significant differences (P < .001) in the bacterial surface coating
      and in the thickness of the biofilm were found between the various ceramic
      materials. The lowest surface coating (19.0%) and biofilm thickness (1.9 MUm)
      were determined on the HIP Y-TZP ceramic; the highest mean values were identified
      with the lithium disilicate glass-ceramic (46.8%, 12.6 MUm). CONCLUSION: Biofilm
      formation on various types of dental ceramics differed significantly; in
      particular, zirconia exhibited low plaque accumulation. In addition to its high
      strength, low plaque accumulation makes zirconia a promising material for various
      indications (including implant abutments and telescopic crowns) that previously
      were met only with metal-based materials.

PMID- 21716985
TI  - Accuracy of dentists in the clinical diagnosis of oral lesions.
AB  - OBJECTIVE: Dentists play an important role in the early diagnosis and treatment
      of oral lesions. However, treatment based solely on a clinical impression of the
      diagnosis, without histologic confirmation, can result in serious consequences,
      particularly when the lesion is precancerous or cancerous. The purpose of this
      study was to determine the overall accuracy of clinical diagnoses made by
      dentists as well as to compare the diagnostic ability of general practitioners
      with members of various dental specialties. METHOD AND MATERIALS: The biopsy
      reports of 976 specimens submitted to the Department of Oral and Maxillofacial
      Pathology, Virginia Commonwealth University School of Dentistry, between January
      2009 and January 2010 were reviewed. The presumptive clinical diagnosis made by
      the practitioner and the final histologic diagnosis on each specimen were
      recorded in addition to whether the submitting dentist was a general practitioner
      or a specialist. RESULTS: Of the clinical diagnoses made by the submitting
      dentists, 43% were incorrect. General dentists misdiagnosed 45.9%, oral and
      maxillofacial surgeons 42.8%, endodontists 42.2%, and periodontists 41.2% of the
      time. The most commonly missed clinical diagnoses were hyperkeratosis (16%),
      focal inflammatory fibrous hyperplasia (10%), fibroma (8%), periapical granuloma
      (7%), and radicular cyst (6%). Cancerous lesions were misdiagnosed 5.6% of the
      time. CONCLUSIONS: The high rates of clinical misdiagnosis by dental
      practitioners indicate that all excised lesions should to be submitted for
      histologic diagnosis.

PMID- 21716986
TI  - Fracture resistance of maxillary premolars with class II MOD cavities restored
      with Ormocer, Nanofilled, and Nanoceramic composite restorative systems.
AB  - OBJECTIVE: To assess the influence of ormocer, nanofilled, nanoceramic, and
      microhybrid composite restorative systems on the fracture resistance of maxillary
      premolars with Class II mesio-occlusodistal (MOD) cavities. METHOD AND MATERIALS:
      Eighty-four sound maxillary human premolars were divided into six groups of 14
      teeth each. Teeth in the first group were left intact and tested as unprepared
      positive controls. Teeth in the remaining five groups were prepared with MOD
      cavities. Teeth in one of the five groups were unrestored and tested as negative
      control. The remaining four groups were restored with an ormocer (Admira), a
      nanofilled composite (Filtek Supreme), a nanoceramic composite (CeramX mono), and
      a microhybrid composite (Tetric Ceram). All groups were stored in water at 37
      degrees C for 24 hours and thermocycled 500 times between 5 degrees C and 55
      degrees C. The specimens were loaded occlusally in a universal testing machine
      using a metal sphere that contacted only the teeth on the cuspal inclines until
      fracture occurred. The results were analyzed by Kruskal-Wallis and Mann-Whitney U
      tests. The level of significance was set at .05. RESULTS: The difference between
      the mean cuspal fracture resistance of the unprepared positive control teeth and
      those restored with ormocer, nanofill, and microhybrid composite was found to be
      statistically significant (P < .05). No statistically significant difference in
      cuspal fracture resistance was found between the unprepared positive control
      teeth and those teeth restored with nanoceramic composite (P > .05). CONCLUSION:
      Under compressive load testing, teeth with microhybrid, ormocer, and nanofilled
      composite restorations had lower cuspal fracture resistance than those with
      nanoceramic composite restorations.

PMID- 21716987
TI  - A rare case of sialolithiasis of the lower lip simulating a mucocele and review
      of the literature.
AB  - Sialolithiasis of the minor salivary glands, especially in the lower lip, is
      rare. We report a case of sialolithiasis of the lower lip simulating a mucocele
      as well as review four additional cases affecting the lower lip and 39 cases
      affecting the upper lip, together with details of the clinical and
      histopathologic findings.

PMID- 21716988
TI  - Pediatric obesity and periodontal disease: a systematic review of the literature.
AB  - OBJECTIVE: Childhood obesity is a looming epidemic affecting western society,
      caused by a sedentary lifestyle and high-energy diet, and is associated with a
      severe morbidity. Obesity in adults has been associated with increased incidence
      and prevalence of periodontal disease. This association is considered to be
      bidirectional: Not only are obese subjects prone to periodontal disease, but
      periodontal disease may also exacerbate dyslipidemia. The objective of this study
      was to review the current literature on the association between obesity and
      periodontal diseases in children. METHODS: Using Medline, Cochrane, and Current
      Contents Clinical Medicine databases, we searched the literature for articles
      published in the English language between 1990 and 2009. Key words used were
      "periodontal disease," "periodontitis," and "tooth loss," linked with "obesity,"
      "BMI," "weight," "overweight," and "children." RESULTS: Only a few relevant
      studies have been conducted in children of specific age groups. Further studies
      are needed to support the hypothesis that obesity in children may be associated
      with increased rates of periodontal disease. CONCLUSION: Since periodontal
      disease is a rare finding in children, general practitioners should be aware of
      the link among obesity, dyslipidemia, and periodontal disease.

PMID- 21716989
TI  - Altered functional activity patterns of fibroblasts related to periodontitis by
      systemic plasminogen deficiency (ligneous periodontitis).
AB  - We report one case of ligneous periodontitis, which is a clinical sign of
      hypoplasmino-genemia. It appears as massive, painless ulcerated gingival
      enlargements and alveolar bone destruction in the affected area. The course of
      the disease is progressive and typically ends with early loss of teeth. At
      present, no efficient treatment option seems to be available. To investigate the
      cause of the rapid bone destruction in this disease, gingival tissue specimens
      were taken from one patient and a healthy control patient to compare the function
      of fibroblastic cells. Our results showed that diseased fibroblasts (1)
      reorganized collagen lattices more rapidly than normal cells, (2) demonstrated a
      greater overall production of pro and active matrix metalloproteinase-2 (MMP-2)
      and increased activation of this protease, and (3) showed a more active phenotype
      than healthy fibroblastic cells. From these preliminary results, there seems to
      be increased MMP-2 production and activation, which might be one compensatory
      (but insufficient) mechanism for the decreased (plasmin-dependent) pericellular
      fibrinolysis in plasminogen-deficient patients. Further studies on this subject
      should evaluate the exact pathomechanism of plasminogen on this enzymatic bone
      and connective tissue destruction.

PMID- 21716990
TI  - A minimally invasive restorative approach for treatment of interproximal root
      caries lesions.
AB  - As the population ages, an increased prevalence of gingival recessions and root
      surfaces exposed to the oral environment has been reported. This in turn causes
      an increased risk for caries; it is estimated that the incidence of root caries
      in those older than 65 years of age is 23.7%. Published data support the use of
      glass ionomer as a restorative material that seems particularly suitable for
      restoring root lesions; the material has good esthetic and anticariogenic
      properties and has gained wide acceptance among practitioners. A minimally
      invasive approach for restoring interproximal root caries lesions with glass
      ionomer is described.

PMID- 21716991
TI  - Solvothermal growth of a ruthenium metal-organic framework featuring HKUST-1
      structure type as thin films on oxide surfaces.
AB  - Phase-pure crystalline thin films of a mixed-valence Ru(2)(II,III) metal-organic
      framework with 1,3,5-benzenetricarboxylate (btc) as a linker were solvothermally
      grown on amorphous alumina and silica surfaces. Based on the Rietveld refinement,
      the structure of Ru-MOF was assigned to be analogous to [Cu(3)(btc)(2)] (HKUST
      1).

PMID- 21716992
TI  - Mesoporous silica nanoparticles as nanocarriers.
AB  - Modern nanomedicine aims at delivering drugs or cells specifically to defective
      cells; therefore, this calls for developing multifunctional nanocarriers for drug
      delivery and cell-tracking. Mesoporous silica nanoparticles (MSNs) are well
      suited for this task. In this feature article, we highlight the strategies in the
      synthesis and functionalization of small, uniform and colloidal stable MSNs. We
      then discuss cell uptake of MSNs and tracking cells, as both aspects are closely
      related to the efficacy of drug delivery and theranostics. Some examples of
      stimulated drug delivery are described. For application considerations, toxicity
      and pharmacokinetics are critical issues and in vivo studies are summarized.

PMID- 21716993
TI  - Polymorphism and isomerisation of an azobenzene derivative on gold.
AB  - M-TBA (4-methoxy-3,30,5,50-tetra-tert-butylazobenzene) adsorbed on a gold (111)
      surface was found to form four different polymorphs, two of which isomerizable at
      -1.7 V, but with a low propensity for further isomerisation of nearby molecules
      (C. Dri, M. V. Peters, J. Schwarz, S. Hecht, L. Grill, Nat. Nanotechnol., 2008,
      3, 649-653). Atomistic simulations investigate the origin of the effects.

PMID- 21716994
TI  - Microfluidic device for analyzing preferential chemotaxis and chemoreceptor
      sensitivity of bacterial cells toward carbon sources.
AB  - We present a novel microfluidic device that enables high sensitive analyses of
      the chemotactic response of motile bacterial cells (Escherichia coli) that swim
      toward a preferred nutrient by sorting and concentrating them. The device
      consists of the Y-shaped microchannel that has been widely used in chemotaxis
      studies to attract cells toward a high concentration and a concentrator array
      integrated with arrowhead-shaped ratchet structures beside the main microchannel
      to trap and accumulate them. Since the number of accumulated cells in the
      concentrator array continuously increases with time, the device makes it possible
      to increase the sensitivity of detecting chemotactic responses of the cells about
      10 times greater than Y-shaped channel devices in 60 min. In addition, the device
      can characterize the relative chemotactic sensitivity of chemoreceptors to
      chemoeffectors by comparing the number of cells in the concentrator array at
      different distances from the channel junction. Since the device allows the
      analysis of both the chemotactic responses and the sensitivity of chemoreceptors
      with high resolution, we believe that not only can the device be broadly used for
      various microbial chemotaxis assays but it also can further the advancement of
      microbiology and even synthetic biology.

PMID- 21716995
TI  - Original phenyl-P(O) bond cleavage at palladium(0): a combined experimental and
      computational study.
AB  - The reaction of the diphosphine-phosphine oxide ligand {[o-iPr(2)P
      (C(6)H(4))](2)P(O)Ph} with Pd(PtBu(3))(2) proceeds with cleavage of the Ph-P(O)
      bond to give an original kappa(P,P(O),P)-pincer complex. According to DFT
      calculations, this oxidative addition occurs via a three-center P,C(ipso),Pd
      transition state.

PMID- 21716996
TI  - Gas phase synthesis and field emission properties of 3D aligned double walled
      carbon nanotube/anatase hybrid architectures.
AB  - A 3D hybrid architecture composed of macroscopic, vertically aligned CNT blocks
      which are formed via a metal catalyzed CVD process followed by deposition of
      TiO(2) on the CNT side walls in nanocrystalline or amorphous form is presented.
      The morphology of the deposited TiO(2) can be tailored by the deposition method
      employed. Depositing TiO(2) from the gas phase by employing the organometallic
      precursor Ti[OCH(CH(3))(2)](4) leads to formation of nanocrystalline anatase or
      rutile particles with a dense coverage on the surface and within the 3D CNT
      scaffold. Phase pure TiO(2) (anatase) is formed between 500 and 700  degrees C,
      while higher temperatures resulted in rutile modification of TiO(2). Below 500 
      degrees C, TiO(2) forms an amorphous oxide layer. At higher temperatures such
      initially formed TiO(2) layers segregate into particles which tend to
      crystallize. In contrast, when generating TiO(2) by oxidation of Ti metal which
      is deposited by vaporization onto the 3D CNT block array, and subsequently
      oxidized in air or controlled O(2) atmosphere this leads to a porous layer with a
      particular nanostructure on top of the CNT blocks. First studies of the
      fabrication and field emission of the new 3D CNT/TiO(2) hybrid cathodes display
      good and stable FE characteristics with onset fields for current density of 1 MUA
      cm(-2) of 1.7 to 1.9 V MUm(-1), while the average field enhancement factor is in
      the range between 2000 and 2500 depending on the O(2) base pressure during the
      measurements.

PMID- 21717003
TI  - Evolution of H5N1 influenza virus through proteotyping of hemagglutinin with high
      resolution mass spectrometry.
AB  - The evolution of the major surface hemagglutinin (HA) antigen of type A H5N1
      influenza viruses is explored at the amino acid level using a new proteotyping
      approach. Alignments of translated hemagglutinin gene sequences of all
      characterised type A H5N1 strains, or subsets thereof, has enabled the presence
      of signature peptides of conserved sequence and unique mass to be investigated
      from the perspective of the host, period and region from which strains were
      isolated. Consistent with the rapid, cross species transmission of H5N1 strains
      among migratory birds, poultry and humans throughout south-east Asia, no
      signatures unique to the host or region were found. Nevertheless, several period
      specific signature peptides were identified that enable strains associated with
      the 1997 H5N1 pandemic to be rapidly differentiated from those in circulation
      across the subsequent decade.

PMID- 21717004
TI  - Chemical activation of MEK1--a redox trigger for evaluating the effects of
      phosphorylation.
AB  - An approach to generate mimics of phosphorylated serine proteins chemically
      through site-specific sulfonation of cysteine is presented. This chemical
      modification is reversible in the presence of reducing agent and therefore is
      analogous to the kinase/phosphatase system used in nature.

PMID- 21717005
TI  - Hierarchically porous nanostructures through phosphonate-metal alkoxide
      condensation and growth using functionalized dendrimeric building blocks.
AB  - Controlled titanium alkoxide mineralization in the presence of phosphonated,
      dendrimeric nano-building blocks provides a new family of hierarchically porous
      dendrimer-bridged titanium dioxide materials.

PMID- 21717006
TI  - Theoretical description of adiabatic laser alignment and mixed-field orientation:
      the need for a non-adiabatic model.
AB  - We present a theoretical study of recent laser-alignment and mixed-field
      orientation experiments of asymmetric top molecules. In these experiments,
      pendular states were created using linearly polarized strong ac electric fields
      from pulsed lasers in combination with weak electrostatic fields. We compare the
      outcome of our calculations with experimental results obtained for the
      prototypical large molecule benzonitrile (C(7)H(5)N) [J. L. Hansen et al., Phys.
      Rev. A, 2011, 83, 023406.] and explore the directional properties of the
      molecular ensemble for several field configurations, i.e., for various field
      strengths and angles between ac and dc fields. For perpendicular fields one
      obtains pure alignment, which is well reproduced by the simulations. For tilted
      fields, we show that a fully adiabatic description of the process does not
      reproduce the experimentally observed orientation, and it is mandatory to use a
      diabatic model for population transfer between rotational states. We develop such
      a model and compare its outcome to the experimental data confirming the
      importance of non-adiabatic processes in the field-dressed molecular dynamics.

PMID- 21717007
TI  - Microwave-assisted C-C bond forming cross-coupling reactions: an overview.
AB  - Among the fundamental transformations in the field of synthetic organic
      chemistry, transition-metal-catalyzed reactions provide some of the most
      attractive methodologies for the formation of C-C and C-heteroatom bonds. As a
      result, the application of these reactions has increased tremendously during the
      past decades and cross-coupling reactions became a standard tool for synthetic
      organic chemists. Furthermore, a tremendous upsurge in the development of new
      catalysts and ligands, as well as an increased understanding of the mechanisms,
      has contributed substantially to recent advances in the field. Traditionally,
      organic reactions are carried out by conductive heating with an external heat
      source (for example, an oil bath). However, the application of microwave
      irradiation is a steadily gaining field as an alternative heating mode since its
      dawn at the end of the last century. This tutorial review focuses on some of the
      recent developments in the field of cross-coupling reactions assisted by
      microwave irradiation.

PMID- 21717008
TI  - Immobilization of Pd nanocatalysts on magnetic rattles and their catalytic
      property.
AB  - Here we report a magnetic composite nanocatalyst (MP@NiSiO/Pd) with a rattle type
      nanostructure. The nickel silicate shell encapsulated magnetic core (MP@NiSiO)
      rattle particles were synthesized by using a facile templating method and the Pd
      nanocrystals with different sizes can be directly immobilized onto the MP@NiSiO
      rattles without using any surfactant or capping reagents. X-Ray powder
      Diffraction (XRD) and Transmission Electron Microscopy (TEM) are employed to
      characterize the rattle type particles. The MP@NiSiO/Pd composites show catalytic
      activity on the Heck and Suzuki reactions. They can be separated from the
      reaction system by using a magnet and the catalyst can be cycled at least for 5
      times.

PMID- 21717009
TI  - A low number of SIC1 mRNA molecules ensures a low noise level in cell cycle
      progression of budding yeast.
AB  - The budding yeast genome comprises roughly 6000 genes generating a number of
      about 10 000 mRNA copies, which gives a general estimation of 1-2 mRNA copies
      generated per gene. What does this observation implicate for cellular processes
      and their regulation? Whether the number of mRNA molecules produced is important
      for setting the amount of proteins implicated in a particular function is at
      present unknown. In this context, we studied cell cycle control as one of the
      highly fine tuned processes that guarantee the precise timing of events essential
      for cell growth. Here, we developed a stochastic model that addresses the effect
      of varying the mRNA amount of Sic1, inhibitor of the Cdk1-Clb5 kinase activity,
      and the resulting noise on Sic1/Clb5 balance at the G1/S transition. We
      considered a range of SIC1 transcripts number according to our experimental data
      derived from the MS2 mRNA tagging system. Computational simulation revealed that
      an increased amount of SIC1 mRNAs lead to an amplified dispersion of Sic1 protein
      levels, suggesting mRNA control being critical to set timing of Sic1
      downregulation and, therefore, S phase onset. Moreover, Sic1/Clb5 balance is
      strongly influenced by Clb5 production in both daughter and mother cells in order
      to maintain the characteristic time of S phase entry overall the population.
      Furthermore, CLB5 mRNA molecules calculated to reproduce temporal dynamics of
      Sic1 and Clb5 for daughter and mother cells agree with recent data obtained from
      more complex networks. Thus, the results presented here provide novel insights
      into the influence that the mRNA amount and, indirectly, the transcription
      process exploit on cell cycle progression.

PMID- 21717010
TI  - Stochastic analysis of a miRNA-protein toggle switch.
AB  - Within systems biology there is an increasing interest in the stochastic behavior
      of genetic and biochemical reaction networks. An appropriate stochastic
      description is provided by the chemical master equation, which represents a
      continuous time Markov chain (CTMC). In this paper we consider the stochastic
      properties of a toggle switch, involving a protein compound (E2Fs and Myc) and a
      miRNA cluster (miR-17-92), known to control the eukaryotic cell cycle and
      possibly involved in oncogenesis, recently proposed in the literature within a
      deterministic framework. Due to the inherent stochasticity of biochemical
      processes and the small number of molecules involved, the stochastic approach
      should be more correct in describing the real system: we study the agreement
      between the two approaches by exploring the system parameter space. We address
      the problem by proposing a simplified version of the model that allows analytical
      treatment, and by performing numerical simulations for the full model. We
      observed optimal agreement between the stochastic and the deterministic
      description of the circuit in a large range of parameters, but some substantial
      differences arise in at least two cases: (1) when the deterministic system is in
      the proximity of a transition from a monostable to a bistable configuration, and
      (2) when bistability (in the deterministic system) is "masked" in the stochastic
      system by the distribution tails. The approach provides interesting estimates of
      the optimal number of molecules involved in the toggle switch. Our discussion of
      the points of strengths, potentiality and weakness of the chemical master
      equation in systems biology and the differences with respect to deterministic
      modeling are leveraged in order to provide useful advice for both the
      bioinformatician and the theoretical scientist.

PMID- 21717011
TI  - Highly active and enhanced photocatalytic silicon nanowire arrays.
AB  - Nanoporous and nonporous three-dimensional silicon nanowire arrays (SiNWAs)
      prepared with metal-assisted chemical etching method were investigated as
      photocatalysts in dye photodegradation systematically. In comparison with
      nonporous SiNWAs, nanoporous SiNWAs have higher surface area, larger pore volume,
      stronger light absorption and better photocatalytic activity. After the HF
      treatment, the photocatalytic activity of all kinds of SiNWAs increased
      significantly and the nanoporous SiNWAs showed excellent stability. The
      photocatalytic activity of different types of SiNWAs with hydrogen surface
      termination can be recovered by HF treatment. This study also reveal that the
      hydrogen terminated surfaces on silicon nanowires (SiNWs) enhance the performance
      of SiNWAs by increasing their photocatalytic activity.

PMID- 21717012
TI  - Engineered nanoparticles for biomolecular imaging.
AB  - In recent years, the production of nanoparticles (NPs) and exploration of their
      unusual properties have attracted the attention of physicists, chemists,
      biologists and engineers. Interest in NPs arises from the fact that the
      mechanical, chemical, electrical, optical, magnetic, electro-optical and magneto
      optical properties of these particles are different from their bulk properties
      and depend on the particle size. There are numerous areas where nanoparticulate
      systems are of scientific and technological interest, particularly in biomedicine
      where the emergence of NPs with specific properties (e.g. magnetic and
      fluorescence) for contrast agents can lead to advancing the understanding of
      biological processes at the biomolecular level. This review will cover a full
      description of the physics of various imaging methods, including MRI, optical
      techniques, X-rays and CT. In addition, the effect of NPs on the improvement of
      the mentioned non-invasive imaging methods will be discussed together with their
      advantages and disadvantages. A detailed discussion will also be provided on the
      recent advances in imaging agents, such as fluorescent dye-doped silica NPs,
      quantum dots, gold- and engineered polymeric-NPs, superparamagnetic iron oxide
      NPs (SPIONs), and multimodal NPs (i.e. nanomaterials that are active in both MRI
      and optical methods), which are employed to overcome many of the limitations of
      conventional contrast agents (e.g. gadolinium).

PMID- 21717013
TI  - Synthesis of hierarchically nanoporous silica films for controlled drug loading
      and release.
AB  - Films with well-controlled porous structures provide many exciting application
      opportunities in chemistry and biology. Here we report the synthesis of a highly
      uniform, hierarchically nanoporous silica film structure, and its application in
      drug loading and release for antibacterial surface coating. Templated by both sub
      micron poly-styrene (PS) particles and a triblock copolymer (F127), this
      hierarchically nanoporous film has two distinct pore sizes of 200 nm and 7 nm.
      The 7-nm mesopores provide high surface area and thus high adsorption capacity
      for drug molecules, and the 200-nm macropores facilitate the adsorption rate of
      drug molecules, especially for molecules with comparable sizes to mesopores.
      Fluorescence measurement of rhodamine release demonstrates that this
      hierarchically porous film has a higher adsorption capacity, efficiency and much
      longer molecule releasing time window than both the inverse opal film and the
      mesoporous film. When loaded with Ampicillin, this hierarchically porous film
      shows over 8 times longer of inhibition of E. coli growth than both the inverse
      opal film and the mesoporous film. This simple and versatile process allows for
      fabrication of a variety of surface-coated, hierarchically nanoporous films with
      different chemical compositions and applications.

PMID- 21717014
TI  - A novel strategy of chemical modification for rate enhancement of 10-23 DNAzyme:
      a combination of A9 position and 8-aza-7-deaza-2'-deoxyadenosine analogs.
AB  - With the help of a divalent-metal ion, 10-23 DNAzyme cleaves RNA. Chemical
      modification of its catalytic loop to make a more efficient enzyme has been a
      challenge. Our strategy started from its five 2'-deoxyadenosine residues (A5, A9,
      A11, A12, and A15) in the loop based on the capability of the N7 atom to form
      hydrogen bonds in tertiary structures. 8-Aza-7-deaza-2'-deoxyadenosine and its
      analogs with 7-substituents (3-aminopropyl, 3-hydroxylpropyl, or phenethyl) were
      each used to replace five dA residues, respectively, and their effect on cleavage
      rate were evaluated under single-turnover conditions. The results indicated that
      the N7 atom of five dA residues were necessary for catalytic activity, and the N8
      atom and 7-substituents were detrimental to the catalytic behavior of 10-23
      DNAzyme, except that all these modifications at A9 were favourable for the
      activity. Especially, DZ-3-9 with 7-(3-aminopropyl)-8-aza-7-deaza-2'
      deoxyadenosine (3) at A9 position gave a 12- fold increase of k(obs), compared to
      the corresponding parent 10-23 DNAzyme. DZ-3-9 was supposed to catalyze the
      cleavage reaction with the same mechanism as 10-23 DNAzyme based on their very
      similar pH-dependent and divalent metal ions-dependent cleavage patterns.
      Introduction of functional groups at A9 position was demonstrated to be a
      successful and feasible approach for more efficient 10-23 DNAzyme analogs.

PMID- 21717015
TI  - Highly enantioselective synthesis of gamma-substituted butenolides via the
      vinylogous Mukaiyama-Michael reaction catalyzed by a chiral scandium(III)-N,N'
      dioxide complex.
AB  - A highly efficient catalytic asymmetric vinylogous Mukaiyama-Michael reaction of
      the 2-silyloxyfuran with chalcone derivatives, catalyzed by a chiral N,N'-dioxide
      scandium(III) complex, has been accomplished which tolerates a wide range of
      substrates. The reaction proceeds with complete regioselectivities, excellent
      diastereoselectivities (up to >99 : 1 dr) and good to excellent
      enantioselectivities (up to 94% ee) under mild conditions, delivering highly
      functionalized enantiomerically enriched anti-gamma-substituted butenolides. The
      process is air-tolerant and easily manipulated with available reagents. In order
      to illustrate the synthetic potential of this reaction, the gram-scale synthesis
      and the elaboration of the butenolides have been explored. On the basis of the
      experimental results, a possible catalytic cycle and favorable stereorecognition
      model have been proposed.

PMID- 21717016
TI  - Microwave-assisted synthesis of dinucleoside analogues containing a thiazolidin-4
      one linkage via one-pot tandem Staudinger/aza-Wittig/cyclization.
AB  - Dinucleosides containing a thiazolidin-4-one linkage were prepared by one-pot
      tandem Staudinger/aza-Wittig/intermolecular cyclization under microwave
      irradiation and their structures were confirmed. Preliminary examination of HIV
      RT inhibition showed that the dinucleosides containing (R)-thiazolidin-4-one
      linkage are significantly more active than those containing (S)-thiazolidin-4-one
      linkage.

PMID- 21717017
TI  - The history of ozone. Part VIII. Photochemical formation of ozone.
AB  - The historical development of the photochemical formation of ozone in the
      atmosphere is outlined, starting from the discovery of ozone by Schonbein in 1843
      and the postulation of its role as UV filter by Hartley in 1881.

PMID- 21717018
TI  - Carbohydrate sensing with a metal-based indicator displacement assay.
AB  - A Pd-based indicator displacement assay for the fluorimetric sensing of
      carbohydrates has been developed. The assay allows the detection of saccharides
      in the low millimolar concentration range in water at neutral pH.

PMID- 21717019
TI  - Smart nanocontainers as depot media for feedback active coatings.
AB  - Among the grand challenges at present are ways to develop systems with low
      consumption of raw materials and with little load on the environment. In view of
      this it is of utmost importance to avoid or to delay processes causing material
      destruction. This is especially urgent, since many protective substances have
      associated health hazards, and new routes to improve the situation are a main
      concern of this contribution. Nanocapsules (nanocontainers) with controlled
      release properties of the shell can be used to fabricate a new family of active
      coatings, with quick response to changes of the coating environment or coating
      integrity. The release of active materials encapsulated into nanocapsules is
      triggered by various external and internal factors, thus preventing spontaneous
      leakage of the active component. The coating can have several active
      functionalities when several types of nanocapsules loaded with corresponding
      active agent are incorporated simultaneously into a coating matrix. We highlight
      recent achievements in development and application of filled responsive
      containers in biomedical and self-healing protective coatings.

PMID- 21717020
TI  - An in vitro and in vivo study of a novel zinc complex, zinc N-(2
      hydroxyacetophenone)glycinate to overcome multidrug resistance in cancer.
AB  - Multiple drug resistance (MDR) remains a major clinical challenge for cancer
      treatment. P-glycoprotein is the major contributor and they exceed their role in
      the chemotherapy resistance of most of the malignancies. Attempts in several
      preclinical and clinical studies to reverse the MDR phenomenon by using MDR
      modulators have not yet generated promising results. In the present study, a co
      ordination complex of zinc viz., Zn N-(2-hydroxyacetophenone)glycinate (ZnNG) has
      been synthesized, characterized and its antitumour activity was tested in vitro
      against drug sensitive and resistant human T-lymphoblastic leukemic cell lines
      (CCRF/CEM and CEM/ADR5000 respectively) and in vivo against Ehrlich ascites
      carcinoma (EAC) implanted in female Swiss albino mice. To evaluate the cytotoxic
      potential of ZnNG, we used sensitive CCRF/CEM and drug resistant CEM/ADR 5000
      cell lines in vitro. Moreover, ZnNG also has the potential ability to reverse the
      multidrug resistance phenotype in drug resistant CEM/ADR 5000 cell line and
      induces apoptosis in combination with vinblastine. ZnNG remarkably increases the
      life span of Swiss albino mice bearing sensitive and doxorubicin resistant
      subline of EAC in presence and in absence of doxorubicin. In addition,
      intraperitoneal application of ZnNG in mice does not show any systemic toxicity
      in preliminary trials in normal mice. To conclude, a novel metal chelate of zinc
      viz., ZnNG, may be a promising therapeutic agent against sensitive as well as
      drug resistant cancers.

PMID- 21717021
TI  - Homoleptic, heteroleptic and mixed-valent thallium and indium complexes of
      multidentate chalcogen-centred PCP-bridged ligands.
AB  - The metathetical reaction of [Li(TMEDA)][HC(PPh(2)Se)(2)] ([Li(TMEDA)]1) with
      TlOEt in a 1:1 molar ratio afforded a homoleptic Tl(I) complex as an adduct with
      LiOEt, Tl[HC(PPh(2)Se)(2)].LiOEt (7), which undergoes selenium-proton exchange
      upon mild heating (60  degrees C) to give the mixed-valent Tl(I)/Tl(III) complex
      {[Tl][Tl{(Se)C(PPh(2)Se)(2)}(2)]}(infinity) (8). Treatment of TlOEt with
      [Li(TMEDA)](2)[(SPh(2)P)(2)CE'E'C(PPh(2)S)(2)] (3b, E' = S; 3c, E' = Se) in a 2:1
      molar ratio produced the binuclear Tl(i)/Tl(i) complexes
      Tl(2)[(SPh(2)P)(2)CE'E'C(PPh(2)S)(2)] (9b, E' = S; 9c, E' = Se), respectively.
      Selenium-proton exchange also occurred upon addition of [Li(TMEDA)]1 to InCl(3)
      to yield the heteroleptic complex (TMEDA)InCl[(Se)C(PPh(2)Se)(2)] (10a). Other
      examples of this class of In(III) complex, (TMEDA)InCl[(E')C(PPh(2)E)(2)] (10b, E
      = E' = S; 10c, E = S, E' = Se) were obtained via metathesis of InCl(3) with
      [Li(TMEDA)](2)[(E')C(PPh(2)E)(2)] (2b, E = E' = S; 2c, E = S, E' = Se,
      respectively). All new compounds have been characterized in solution by (1)H and
      (31)P NMR spectroscopy and the solid-state structures have been determined for 8,
      9c and 10a-c by single-crystal X-ray crystallography. Complex 8 is comprised of
      Tl(+) ions that are weakly coordinated to octahedral [Tl{(Se)C(PPh(2)Se)(2)}(2)](
      ) anions to give a one-dimensional polymer. The complex 9c is comprised of two
      four-coordinate Tl(+) ions that are each S,S',S'',Se bonded to the hexadentate
      [(SPh(2)P)(2)CSeSeC(PPh(2)S)(2)](2-) ligand in which d(Se-Se) = 2.531(2) A. The
      six-coordinate In(III) centres in the distorted octahedral complexes 10a-c are
      connected to a tridentate [(E')C(PPh(2)E)(2)](2-) dianion, a chloride ion and a
      neutral bidentate TMEDA ligand.

PMID- 21717022
TI  - Complexome of Escherichia coli cytosolic proteins under normal native conditions.
AB  - The interactions between proteins are important for the majority of biological
      functions and the interacting proteins are usually assembled into a complex.
      Knowing a set of protein complexes of a cell (complexome) is, therefore,
      essential for a better understanding and global view of cell functions. To
      visualize and identify the protein complexome of E. coli K-12 under normal native
      conditions on a proteome-wide scale, we developed an integrated proteomic
      platform with the combination of 2-D native/SDS-PAGE-based proteomics with co
      immunoprecipitation, far-Western blotting, His-tag affinity purification and
      functional analysis, and used it to investigate the E. coli cytosolic complexome.
      A total of 24 distinct heteromeric and 8 homomeric protein complexes were
      identified. These complexes mainly contributed to glycolysis/gluconeogenesis,
      bioinformation processing, and cellular processes. Of the 24 hetereomeric
      complexes, 16 were reported for the first time, and 2 known complexes contained
      novel components that have not been reported previously based on DIP database
      search. Among them, RpoC-RpsA-Tig-GroL was found to be involved in
      transcriptional and co-translational folding, and EF-G-TufA-Tsf-RpsA linked a
      protein synthesis site with protein translational elongation factors. This
      systematic proteome analysis provides new insights into E. coli molecular systems
      biology.

PMID- 21717023
TI  - Surface active benzodiazepine-bromo-alkyl conjugate for potential GABAA-receptor
      purification.
AB  - A conjugable analogue of the benzodiazepine 5-(2-hydroxyphenyl)-7-nitro
      benzo[e][1,4]diazepin-2(3H)-one containing a bromide C(12)-aliphatic chain (BDC)
      at nitrogen N1 was synthesized. One-pot preparation of this benzodiazepine
      derivative was achieved using microwave irradiation giving 49% yield of the
      desired product. BDC inhibited FNZ binding to GABA(A)-R with an inhibition
      binding constant K(i) = 0.89 MUM and expanded a model membrane packed up to 35 mN
      m(-1) when penetrating in it from the aqueous phase. BDC exhibited surface
      activity, with a collapse pressure pi = 9.8 mN m(-1) and minimal molecular area
      A(min) = 52 A(2)/molecule at the closest molecular packing, resulted fully and
      non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x?
      0.1. A geometrical-thermodynamic analysis along the pi-A phase diagram predicted
      that at low x(BDC) (<0.1) and at all pi, including the equilibrium surface
      pressures of bilayers, dpPC-BDC mixtures dispersed in water were compatible with
      the formation of planar-like structures. These findings suggest that, in a
      potential surface grafted BDC, this compound could be stabilize though London
      type interactions within a phospholipidic coating layer and/or through halogen
      bonding with an electron-donor surface via its terminal bromine atom while
      GABA(A)-R might be recognized through the CNZ moiety.

PMID- 21717024
TI  - Cubic and doubly-fused cubic samarium clusters from Sm(II)-mediated reduction of
      organic azides and azobenzenes.
AB  - A polynuclear samarium imido complex [(L)Sm(4)(MU(3)-NSiMe(3))(4)] (2) featuring
      a cubane-like cluster has been synthesized from the reaction of an organic azide
      and a samarium(II) complex [(L)SmI(2)Li(2)(THF)(Et(2)O)(2)] (1). In addition,
      this divalent samarium starting material (1) reacts with azobenzene to give the
      first example of a well-defined doubly-fused cubic imido-cluster [(L)Sm(6)(MU(3)
      NPh)(4)(MU(4)-NPh)(2)I(2)(THF)(2)] (4) in addition to a major cubic complex
      [(L)Sm(4)(MU(3)-NPh)(4)] (3).

PMID- 21717025
TI  - Pt based nanocomposites (mono/bi/tri-metallic) decorated using different carbon
      supports for methanol electro-oxidation in acidic and basic media.
AB  - Pt based mono/bi/tri-metallic nanocomposites on different carbon based supports
      (activated carbon (AC), carbon nanotubes (CNTs) and carbon nanofibers (CNFs))
      were synthesised and Pt surface enrichment achieved. The overall theoretical
      metallic content (Pt + Au + Sn) was 20% (w/w) in all mono/bi/tri-metallic
      nanocomposites and was found to be uniformly distributed in the supporting matrix
      (80%). The surface morphology and composition of the synthesised materials was
      characterised using scanning electron microscopy (SEM), energy-dispersive X-ray
      spectrometry (EDX), transmission electron microscopy (TEM), Fourier transform
      infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), X-ray
      diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), while cyclic
      voltammetry was employed in order to confirm their typical metallic
      electrochemical characteristics. Electrochemical measurements indicated that
      Pt(2)Au(1)Sn(1) trimetallic catalysts demonstrated a significantly higher
      electrochemically active surface area relative to activated carbon supported PtAu
      based bimetallic counterparts. The results show that the CNT based trimetallic
      catalyst (Pt(2)Au(1)Sn(1)/CNT) showed greatest electroactive surface area (49.3
      m(2)/g) and current density for methanol oxidation in acidic (490 mA mg(-1) Pt)
      as well as basic (1700 mA mg(-1) Pt) conditions. Results demonstrated that in
      comparison to Au/C and Sn/C (no/negligible response), the presence of a small
      amount of Pt in the Au and Sn based nanocomposites, significantly modified the
      catalytic properties. The activated carbon supported bimetallic (Pt(1)Au(3)/C)
      catalyst showed reasonably good response (260 mA mg(-1) Pt) among all bimetallic
      nanomaterials examined. The current response achieved for Pt(2)Au(1)Sn(1)/CNT was
      1.9 times (in acidic media) and 2.1 times (in basic media) that for synthesised
      Pt/C in terms of per mg Pt activity. Overall the methanol oxidation studies
      demonstrated that the presence of Au and Sn in Pt based catalysts strongly
      indicated their capacity to reduce the precious Pt content required for this
      application, demonstrating the role of Au in improving current/potential response
      and signifying the importance of supporting matrices.

PMID- 21717026
TI  - Anchoring of self-assembled monolayers of unsymmetrically-substituted
      chromophores with an oxoporphyrinogen surface clamp.
AB  - Multichromophoric molecules of conjugated N-substituted oxoporphyrinogens have
      been assembled on the Au(111) surface using solution and sublimation techniques.
      The operation of the oxoporphyrinogen moiety as a surface anchoring unit in the
      formation of molecular monolayers has been demonstrated.

PMID- 21717027
TI  - A simple synthesis of a targeted drug delivery system with enhanced cytotoxicity.
AB  - A simple synthesis of a targeted drug delivery system with enhanced cytotoxicity
      to (epidermal growth factor receptor) EGFR(+) cancer cells.

PMID- 21717028
TI  - On-line, real time monitoring of exhaled trace gases by SIFT-MS in the
      perioperative setting: a feasibility study.
AB  - A study is described of the first on line, real time analyses of the exhaled
      breath of five anaesthetized patients during the complete perioperative periods
      of laparoscopic surgery. These breath analyses were achieved using a selected ion
      flow tube, SIFT-MS, instrument, located in the operating theatre at an acceptable
      distance from the operating table, and coupled to the endotracheal tube in the
      ventilation circuit via a 5 metre long capillary tube. Thus,
      inhalation/exhalation breathing cycles, set to be at a frequency of 10 per
      minute, were sampled continuously for water vapour, the metabolites acetone and
      isoprene and the propofol used to induce anaesthesia for each operating period
      that ranged from 20 min (shortest) to 80 min (longest). Whilst there was some
      loss of water vapour along the long sampling line, the concentrations of the
      other trace compounds were not diminished. The breath acetone was essentially at
      a constant level for each patient, but increased somewhat over the longest
      operating period due to the onset of lipolysis. Most interesting is the clear
      increase of breath isoprene following abdomen inflation with carbon dioxide. The
      vapour of the intravenously injected propofol was detected in the exhaled breath
      and remained essentially constant during the perioperative period. These analyses
      were performed totally non-invasively and the data were immediately and
      constantly available to the anaesthetist and surgeon. Exploitation of this
      development could influence decision making and potentially improve patient
      safety within the perioperative setting.

PMID- 21717029
TI  - Flexible and transparent graphene films as acoustic actuator electrodes using
      inkjet printing.
AB  - Flexible and transparent graphene films have been fabricated via inkjet printing
      and vapor deposition (VDP) methods, and the graphene-based acoustic actuator
      could be used as an extremely thin and lightweight loudspeaker.

PMID- 21717030
TI  - Kinetic discrimination in recognition of DNA quadruplex targets by guanine-rich
      heteroquadruplex-forming PNA probes.
AB  - Guanine-rich peptide nucleic acid probes hybridize to DNA G quadruplex targets
      with high affinity, forming PNA-DNA heteroquadruplexes. We report a surprising
      degree of kinetic discrimination for PNA heteroquadruplex formation with a series
      of DNA targets. The fastest hybridization is observed for targets folded into
      parallel morphologies.

PMID- 21717031
TI  - Surface modification of TiO2 with metal oxide nanoclusters: a route to composite
      photocatalytic materials.
AB  - Density functional theory simulations show that modifying rutile TiO(2) with
      metal oxide nanoclusters produces composite materials with potential visible
      light photocatalytic activity.

PMID- 21717032
TI  - Selective synthesis of poly-substituted fluorine-containing pyridines and
      dihydropyrimidines via cascade C-F bond cleavage protocol.
AB  - Fluorinated azaheterocycles are frequently found in pharmaceuticals, drug
      candidates, ligands for transition metal catalysts, and other molecular
      functional materials, so efficient methods for the synthesis of these compounds
      are of significant value. We herein describe a selective strategy for the
      synthesis of poly-substituted pyridines and fluoroalkyl dihydropyrimidines based
      on C-F bond breaking of the anionically activated fluoroalkyl group. An array of
      pyridines and dihydropyrimidines were prepared through this domino process in
      high yields under noble metal catalyst-free conditions, making this method a
      valuable supplement to azaheterocycle synthesis.

PMID- 21717033
TI  - Facile synthesis of carbohydrate-integrated isoxazolines through tandem [4+1]
      cycloaddition and rearrangement of 2-nitroglycals.
AB  - Carbohydrate-integrated isoxazolines were synthesized from 2-nitroglycals and
      sulfur ylides, with the aid of 1-phenylthiourea catalyst. The reactions proceeded
      via [4+1] annulations and upon subsequent rearrangement, afforded the
      corresponding isoxazolines in high yields with excellent diastereoselectivities
      (up to 95% de).

PMID- 21717034
TI  - Severe alterations in lipid composition of frontal cortex lipid rafts from
      Parkinson's disease and incidental Parkinson's disease.
AB  - Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide
      a highly saturated and viscous physicochemical microenvironment to promote
      protein-lipid and protein-protein interactions. We purified lipid rafts from
      human frontal cortex from normal, early motor stages of Parkinson's disease (PD)
      and incidental Parkinson's disease (iPD) subjects and analyzed their lipid
      composition. We observed that lipid rafts from PD and iPD cortices exhibit
      dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated
      fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid
      (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher
      than in control brains. Paralleling these findings, unsaturation and
      peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid
      classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine
      and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and
      sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint
      a dramatic increase in lipid raft order due to the aberrant biochemical structure
      in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal
      cortex occur at early stages of PD pathology. The findings correlate with
      abnormal lipid raft signaling and cognitive decline observed during the
      development of these neurodegenerative disorders.

PMID- 21717035
TI  - Tissue factor-dependent chemokine production aggravates experimental colitis.
AB  - Tissue factor (TF) is traditionally known as the initiator of blood coagulation,
      but TF also plays an important role in inflammatory processes. Considering the
      pivotal role of coagulation in inflammatory bowel disease, we assessed whether
      genetic ablation of TF limits experimental colitis. To this end, wild-type and TF
      deficient (TFlow) mice were treated with 1.5% dextran sulfate sodium (DSS) for 7
      d, and effects on disease severity, cytokine production and leukocyte recruitment
      were examined. Clinical and histological parameters showed that the severity of
      colitis was reduced in both heterozygous and homozygous TFlow mice compared with
      controls. Most notably, edema, granulocyte numbers at the site of inflammation
      and cytokine levels were reduced in TFlow mice. Although anticoagulant treatment
      with dalteparin of wild-type mice reduced local fibrin production and cytokine
      levels to a similar extent as in TFlow mice, it did not affect clinical and
      histological parameters of experimental colitis. Mechanistic studies revealed
      that TF expression did not influence the intrinsic capacity of granulocytes to
      migrate. Instead, TF enhanced granulocyte migration into the colon by inducing
      high levels of the granulocyte chemoattractant keratinocyte-derived chemokine
      (KC). Taken together, our data indicate that TF plays a detrimental role in
      experimental colitis by signal transduction-dependent KC production in colon
      epithelial cells, thereby provoking granulocyte influx with subsequent
      inflammation and organ damage.

PMID- 21717036
TI  - [Prevalence of Mood Disorders in a university students population].
AB  - AIMS: To evaluate (i) the incidence of psychiatric disorders and (ii) the
      frequency of Mood Disorders diagnoses in a sample of 115 university students
      afferent to Sportello Counseling-Accoglienza Studenti "Fatti vivo!" of "Sapienza"
      University of Rome, between November 2008 and December 2010; to point out
      correlations with socio-demographic variables. MATERIALS AND METHODS: The
      prevalence of Mood Disorders was evaluated with the Structured Clinical Interview
      for DSM IV Axis I Disorders Clinical Version (SCID-I cv), drawn up by the
      counselor at first meeting. Each student completed a data collection from which
      investigates socio-demographic characteristics. A descriptive analysis was
      conducted and the associations between variables and Axis I diagnoses were
      investigated. RESULTS: The overall mean age is 24.7 years. A DSM IV-TR Axis I
      Disorder was diagnosed in 26.9%, of which 45.2% is constituted by Mood Disorders
      (mean age of 25.7 years). Male students, the highest family members' mean age and
      the lowest regular studies (64% pursue a course of regular studies) seem to be
      characteristics of the subgroup of students with Mood Disorders diagnoses
      compared to the subgroups with other Axis I Disorders diagnoses. Moreover, the
      same subgroup most frequently recognizes as pathological its condition (78.6%)
      compared to the subgroup with other Axis I Disorders diagnoses (53.3%). Those
      differences, however, aren't statistically significant. CONCLUSIONS: The
      discovered percentage of Axis I diagnoses in general and Mood Disorders in
      particular could be considered representative of perceived unease degree in a
      population of university students. At the same time, the difficulty in
      identifying the early signs of uneasiness and in recognizing as pathological own
      condition interferes with and delays the awareness of the need of a
      psychological/psychiatric support and the expression of the help-seek.

PMID- 21717037
TI  - [The syncope in Emergency Department: usual management vs guidelines].
AB  - INTRODUCTION: The syncope is a common cause of admission to Emergency
      Departments, representing around 1-3% of all admissions to the service. However,
      elderly age and important comorbidities often hinder a definite etiologic
      diagnosis, with increasing requests for diagnostic tests and longer periods of
      hospitalization. MATERIALS AND METHODS: We analyzed the management of 1,204
      patients admitted to our Emergency Department for transient loss of consciousness
      in the period between 1 June 2009 and 1 June 2010, evaluating the following
      parameters: average age, gender, triage color code at admittance, performed
      diagnostic tests, diagnosis at discharge from ED and destination ward. We also
      studied a subgroup of 93 patients admitted to emergency medicine units evaluating
      their OESIL score at admittance, comorbidities, performed diagnostic tests and
      diagnosis at discharge from the ward. RESULTS: In the Emergency Department, 45%
      of patients were discharged with a diagnosis of syncope of unknown origin; in 21%
      of patients syncope was excluded; 19% of patients received a diagnosis of
      cardiogenic syncope; 11% were diagnosed with a presyncope; 3% with orthostatic
      hypotension and 1% with vasovagal syncope. In emergency medicine units, 51% of
      patients were discharged with a diagnosis of cardiogenic syncope, 11% were
      diagnosed with vasovagal syncope, 11% with presyncope, 11% with TIA, 8% with loss
      of consciousness non-syncope and 8% with syncope of unknown origin. CONCLUSIONS:
      Management of patients with syncope, elderly people with important comorbidities
      in particular, is still a serious problem for the emergency physician. The
      creation of specialized units for the management of syncope, the so-called
      syncope units, through the implementation of a shared diagnostic and therapeutic
      protocol, aims at reducing inappropriate hospitalization and average length of
      stay.

PMID- 21717038
TI  - Evaluation of natural reductants protecting red blood cell membranes against
      oxidative damage in psoriatic patients.
AB  - OBJECTIVE: Psoriasis is a chronic skin disease and one of its main causes could
      be the oxidative stress. The use of natural reductants, in the treatment of
      several diseases, is well known but the effects of such treatments on the chronic
      psoriasis are not clear. The aim of this study is to evaluate the efficacy of the
      treatment with organic matrix, deriving from micro-flora, grown in shallow hyper
      thermal water tubs at Guardia Piemontese-Acquappesa (CS) Italy, in patients
      affected by moderate psoriasis. MATERIALS AND METHODS: The study has been
      performed on 10 subjects with plaque psoriasis and on 10 healthy control
      subjects. Clinical severity of psoriasis was determined according to Psoriasis
      and Severity Index (PASI). The treatment efficacy was observed trough the
      evaluation of membrane fluidity, by fluorescence polarization, lipid
      peroxidation, anion permeability and haemolysis in red blood cells. RESULTS:
      After 12 days of patients' treatment, a significant reduction of PASI score was
      observed, this result is supported by a significant improvement of all studied
      parameters. CONCLUSIONS: The results, obtained by the evaluation of all studied
      parameters in patients treated with the organic matrix, are evidence of the
      efficacy of this treatment, according to PASI evaluation. Thus our results,
      suggest that this therapeutic line may be useful in the treatment of moderate
      psoriatic lesions and also in improving the life quality of psoriatic patients.

PMID- 21717039
TI  - Chronic urticaria and IgG paraproteinaemia: unusual spectrum of Schnitzler
      Syndrome.
AB  - Schnitzler Syndrome (SS) is a rare clinical entity of unknown etio-pathogenesis
      characterizated by non itching chronic urticaria, associated with an IgM
      monoclonal paraprotein; other symptoms as bone pain, poliarthralgia, elevated
      erytrocyte sedimentation rate and persistent fever, may be present. Since 1972
      1974, when it was first described by Schnitzler et al. about 80 cases have been
      reported in literature, all characterized by chronic urticaria and IgM monoclonal
      gammopathy. Nashan et al, were the first to publish a case of SS with a benign
      monoclonal IgG, composed by light -kappa- chains. We described two cases of
      chronic non itching urticaria with the same symptoms above mentioned, but an IgG
      monoclonal paraprotein instead of IgM gammopathy. Therefore in according to
      Nashan et al, we suggest that the spectrum of SS should include patients that
      present the same clinical picture described in 1972 in association with either
      IgM or IgG gammopathy.

PMID- 21717040
TI  - Henoch-Schonlein purpura in a patient with bowel bypass syndrome.
AB  - Henoch-Schonlein purpura (HSP) is a common vasculitis being characterized by the
      classic tetrad of nonthrombocytopenic palpable purpura, arthritis or arthralgias,
      gastrointestinal and renal involvement. Antigen-antibody (IgA) complexes activate
      the alternative complement pathway, resulting in inflammation and small vessels
      vasculitis. We present the case of a 53 years old Italian woman with HSP who was
      previously hospitalized for purpura skin lesions of the lower legs and diarrhea;
      a skin biopsy showed a leukocytoclastic vasculitis with perivascular accumulation
      of neutrophils and mononuclear cells. She was treated with immunosuppressive
      therapy. After 8 months she was hospitalized again for a recurrent episode of
      purpura skin lesions of the lower legs. At age 49 she was affected by obesity
      (BMI = 41.6 Kg/m2), treated via a bilio-pancreatic diversion that led, within a
      year, to a BMI reduction (25 Kg/m2). We suppose that bariatric surgery played a
      role on the development of autoimmune phenomena and that the formation of
      immunecomplexes is secondary to the excess of intestinal bacterial antigens. A
      cyclic therapy with Paromomicine 500 mg twice daily and Metronidazole 250 mg
      twice daily was performed with a clear up of the clinical picture. In medical
      literature are described numerous complications which include arthritis, erythema
      nodosum-like lesions, eruptions and other skin manifestations in patients who
      have undergone jejunocolic bypass. This case report describes for the first time
      the presence of HSP in a patient with bowel bypass syndrome and it is also able
      to demonstrate the relationship between the intestinal bacterial overgrowth and
      the systemic autoimmune system.

PMID- 21717041
TI  - A world wide public health problem: the principal re-emerging infectious
      diseases.
AB  - The extraordinary progress in the knowledge of infectious disease, the discovery
      of antibiotics and effective vaccines are among the great achievement of the
      nineteenth and twentieth centuries. These achievement have led to a dramatic
      reduction in the levels of mortality from these diseases. According to the World
      Health Organization, the term "re-emerging infectious diseases" refers to
      infectious diseases, which although well known, have not been of recent public
      health importance. However, climate change, migration, changes in health
      services, antibiotic resistance, population increase, international travel, the
      increase in the number of immune-depressed patients ,etc have lead to the re
      emergence of these diseases. The climate changes are exposing sectors of the
      population to inadequate fresh air, water, food and resources for survival which,
      in consequence, provoke increases in both internal and international migration.
      In this particular period in which we find ourselves, characterized by
      globalization, the international community has become aware that the re-emergence
      of these diseases poses an important risk for public health underlines the
      necessity to adopt appropriate strategies for their prevention and control. The
      re-emerging diseases of the twenty-first century are a serious problem for public
      health and even though there has been enormous progress in medical science and in
      the battle against infectious diseases, they are still a long way from being
      really brought under control. A well organized monitoring system would enable the
      epidemiological characteristics of the infectious diseases to be analyzed and the
      success or otherwise of preventive interventions to be precisely evaluated. For
      this reason, the World Health Organization and the European Union have discussed
      the formation of a collaborative network for the monitoring and control of re
      emerging diseases and has initiated special programmes. The battle between
      humanity and infectious disease has a history lasting thousands of years and is
      destined to continue in the future emphasizing the need to adopt combined
      policies for the prevention and control of re-emerging diseases.

PMID- 21717042
TI  - A brief history of the Quality of Life: its use in medicine and in philosophy.
AB  - The term Quality of Life (QoL) has been increasingly used in medical and
      philosophical literatures for the past four decades. The purpose of this article
      is to analyze how QoL is being used in medicine and in philosophy to understand
      its current status. In the 1960s and 1970s new technologies raised new questions
      for clinicians, so they used QoL as a parameter for making decisions in health
      issues. Consequently, researchers focused their interest on the construction and
      testing of instruments designed to measure health and QoL. However, all these
      instruments showed some conceptual and methodological problems that made the use
      of QoL in medicine difficult. While some researchers considered QoL an
      "idiosyncratic mystery", others believed that QoL was useful in implementing the
      patient's point of view into clinical practice and they suggested improving QoL's
      definition and methodology. In the 1980s, some consequentialist philosophers used
      QoL to formulate moral judgment, in particular they justified infanticide for
      some severely handicapped infants, and both euthanasia and suspension of life
      sustaining treatment using QoL. In the 1990s, welfarist philosophers opened a new
      debate about QoL and they associated it with health and happiness. These
      philosophers developed QoL and those other concepts as subjectivist notions;
      consequently their definition and their measurements pose challenges. Afterwards
      researchers' interest in theoretical issues regarding QoL has fallen;
      nevertheless, physicians have continued to use QoL in clinical practice.

PMID- 21717043
TI  - Anti-inflammatory effect of Curcuma longa (turmeric) on collagen-induced
      arthritis: an anatomico-radiological study.
AB  - INTRODUCTION AND OBJECTIVE: Curcuma longa (CL) or turmeric is an Ayurvedic herb
      that has been traditionally used to treat inflammatory conditions like rheumatoid
      arthritis (RA). Collagen-induced arthritis (CIA) is a well established
      experimental auto-immune mediated polyarthritis in susceptible strains of
      rodents. The main aim of the study was to observe the inflammatory, macroscopic
      and radiological changes in the arthritic ankle joints of experimentally collagen
      induced arthritis animals treated with or without CL extract. MATERIALS AND
      METHODS: Thirty six male Sprague-Dawley (6-8 weeks-old, 150 +/- 50) rats were
      equally divided into six groups. The first group served as a control while the
      rest five groups were immunized subdermally with 150 ug collagen type-II on day
      0. All rats with established CIA with arthritis score (AS) exceeding 1 were
      treated orally with betamethasone (0.5 mg/ml/kg body weight) and varying doses of
      CL extract (30, 60 and 110 mg/ml/kg body weight) using olive oil as vehicle,
      daily for four weeks. Arthritic scoring (AS) of the paws, measurement of
      erythrocyte sedimentation rate (ESR) and paw thickness and radiological scoring
      were performed. RESULTS: Treatment with 110 mg/ml/kg CL showed significant mean
      difference in the ESR (p<0.01), AS (p<0.05) and radiological scores (p<0.01) on
      day-28 compared to the vehicle treated group. The mean difference for the ESR, AS
      and radiological scores of this highest CL dose group were found to be
      insignificant compared to the betamethasone treated group. CONCLUSION: The
      administration of CL extract arrested the degenerative changes in the bone and
      joints of collagen-induced arthritic rats.

PMID- 21717044
TI  - The ideal measurement of the quality of life in post stroke patients: an urban
      study.
AB  - OBJECTIVE: There is paucity of literature on the measurement of the quality of
      life in post stroke patients in the developing countries. The main objective of
      this study was to determine the quality of life (QOL) of post stroke patients.
      MATERIALS AND METHODS: A cross-sectional study was conducted on 107 post stroke
      patients in two centers. The data was obtained during the period of January 2009
      till May 2009 using purposive sampling method. A total of 68 males and 39 females
      participated in this study. Stroke Specific Quality Of Life (SS-QOL) version 2.0
      was used. Cronbach's alpha values for SS-QOL ranged between 0.73 and 0.89.
      RESULTS: The mean +/- SD of the QOL score was 141.79 +/- 40.32. The mean +/- SD
      of the age was 65.47 +/- 11.79 years. Result showed significant negative
      association between age and QOL of post stroke patients (r = - 0.199, p= 0.040).
      Domains mostly affected by stroke compared to pre-stroke were mobility (69%) and
      energy (64%). There were two domains in SS-QOL significantly predicted the QOL of
      post stroke patients. These domains were work and productivity (beta= 2.277, t=
      2.145, p= 0.035) and thinking (beta= 1.927, t= 2.567, p= 0.012). CONCLUSION: Few
      items from this measurement tool may not be appropriate in a developing country
      because of the different cultural background. There is a need to develop
      appropriate post stroke patient measurement tool based on local practice.

PMID- 21717045
TI  - The quality of life among coronary heart disease patients at a teaching hospital.
AB  - BACKGROUND AND AIMS: Quality of life after acute coronary heart disease amongst
      patients is important outcome factor in deliberations of patient's care. The main
      aim of the study was to examine the quality of life amongst acute CHD patients.
      MATERIALS AND METHODS: A cross sectional descriptive study was conducted after an
      acute attack amongst coronary heart disease (CHD) patients in Universiti
      Kebangsaan Malaysia Medical Centre (UKMMC).The Medical Outcomes Short Form 36 (SF
      36) comprised of 36 items used to measure quality of life which comprised of 4
      domains of physical component summary were physical function, role physical,
      bodily pain, and general health and 4 domains of mental component summary were
      vitality, social function, emotional role, and mental health. A total of 108
      respondents were recruited for this study. RESULTS: The findings showed that CHD.
      Respondents possessed good level of quality of life with total score of (59 +/-
      22). The total score of physical domain had mean and SD of 56 +/- 24, while the
      total scores of the mental domain had mean and SD of 62 +/- 27. There were
      significant differences between the general health components of quality of life
      with educational status of the CHD patients with (F= 5.433, p<0.05). There were
      significant differences in role physical components of quality of life with
      income (F= 3.144, p<0.05). CONCLUSION: The cardiac rehabilitation program would
      have deliberately improved their needs and conditions whilst hospitalization.
      These results have implications in which CHD patients should be evaluated with
      regard to their continuity of care.

PMID- 21717046
TI  - Unusual grooved styloid process in a human skull: morphological details and
      clinical implications.
AB  - The temporal Styloid Process is an important anatomical landmark for surgeons
      while performing skull based surgery, for anaesthetists while injecting local
      anaesthetic solution and for radiologists during interpretation of CT and MRI
      scans. Knowledge of morphological variations of the styloid process such as a
      unique groove on its posterior aspect as seen in the present case not only has
      great clinical implications but is also of academic interest. The present article
      describes in detail an unusual groove in the styloid process with an additional
      anterior angulation at its tip. The morphological features, embryological basis
      and clinical relevance is discussed in details.

PMID- 21717047
TI  - A case report of a difficult dissection of the iliac vessels conducted by means
      of the harmonic scalpel during a kidney transplantation.
AB  - BACKGROUND: The "difficult" preparation of iliac vessels in the kidney transplant
      recipient caused by a perivascular fibrosis with satellite lymphadenopathy is
      sometimes burdened by post-transplant complications (lymphocele, seroma and
      hematoma). Both iliac vascular adhesions and satellite lymphoadenopaty are often
      due to reiterate femoral cannulation aimed to hemodialysis. PATIENTS AND METHODS:
      The case report concerns a 60 years old female uremic patient, on dialysis for
      about 4 years with perivascular fibrosis and pelvic lymphadenopathy caused by
      bilateral femoral artery catheterization. In the course of kidney transplant,
      preparation of the iliac vessels was performed by ultrasonic scalpel. In the case
      we handled there was no incidence of immediate, medium and long term post
      operative complications, with a considerable reduction of the operative time in
      the vascular dissection performed without ligation. Often the long dialytic
      period, the same nephropathy, reiterative femoral catheterization determine
      perivascular fibrosis and/or consensual lymphadenopathy. In these cases, in light
      of initial experience, the use of ultrasonic scalpel enables easy dissection by
      the coagulative synthesis not only of vascular compartment but also of the
      lymphatic duct whose leakage, particularly in these cases, creates a favourable
      condition to hematoma and/or lymphocele formation. These complications, although
      rarely jeopardize patient's life, however, may affect the outcome of
      transplantation in terms of morbidity and survival of the organ. The use of
      ultrasonic scalpel ensures total control of vascular and lymphatic compartment
      coagulation, alongside a reduction in the time of surgical dissection.

PMID- 21717048
TI  - Use of neutral protamine lispro (NPL) insulin in a patient affected by acute
      pancreatitis under parenteral nutrition.
AB  - Hyperglycaemia is considered the main obstacle to the activation of a correct
      nutritional support, even in patients not affected by diabetes mellitus. The
      stress associated with the acute pathology stimulates controinsular hormones and
      causes modifications in the glucidic metabolism. Artificial nutrition (AN), both
      enteral and parenteral (PN), is considered one of the main causes of
      hyperglycaemia in hospitalized patients. ADI-AMD recommendations underline that a
      long-acting insulin analogues can be used on a stabilized patient supported with
      PN via peristaltic pump. In the following case report, a patient under PN was
      given, after a surgery for acute pancreatitis, an injectable suspension of lispro
      NPL insulin. Our case report shows that also NPL lispro insulin subcutaneously
      can be used in patients under PN who need an insulin treatment and who can use a
      constant-flow infusion pump. Thanks to initial observations on the use of NPL
      insulin lispro in patients under PN we can assume the importance of such an
      insulin in association with AN. Clin Ter 2011; 162(3):231-234.

PMID- 21717049
TI  - Clinico-anatomical report of a rare anomalous disposition of brachioradialis: a
      possible site for compressing superficial branch of radial nerve.
AB  - The topography of the neurovascular structures in the antebrachium assumes
      relevance during surgical approaches in this region. The aim of the present case
      report was to describe the clinical importance of a bifid brachioradialis with
      the superficial branch of radial nerve entrapped between the two slips. The
      insertion of the two slips was unusual and merits a special documentation in
      anatomy literature. We propose that the superficial branch of radial nerve could
      possibly be subjected to compression resulting in the neurological symptoms of
      varying magnitude. A precise working knowledge of the nerves and muscles of the
      antebrachium and elbow region is vital for the operating surgeons to avoid post
      operative complications.

PMID- 21717050
TI  - Accessory osseous passages in the vicinity of foramen rotundum in a dry adult
      human skull: morphological evaluation, embryological correlation and clinical
      reappraisal.
AB  - An unusual bony depression with accessory osseous passages in the right side of
      middle cranial fossa was observed in a dry adult human skull. It was located
      below the superior orbital fissure and optic canal. The bony depression was
      divided into two parts ,medial and lateral fossa, by an incomplete oblique bony
      septum. The foramen rotundum and an accessory bony canaliculus were present in
      the medial fossa whereas the lateral fossa was blind. The foramen rotundum led as
      usual into the pterygopalatine fossa . The presence of such an abnormal bony
      depression in the right middle cranial fossa with accessory osseous passages in
      the vicinity of the foramen rotundum is highlighted in the present case, with
      embryological correlation and clinical relevance. Anatomical awareness of such
      variations in the middle cranial fossa are important for the present day
      radiologist who interprets imaging for this area, neurosurgeons , who operate in
      this area in the vicinity of cavernous sinus and anaesthetists, during regional
      block anaesthesia.

PMID- 21717051
TI  - An accessory venous channel of abdomen: an anatomical insight.
AB  - Variations in the venous architecture of the retro peritoneum is not uncommon,
      mostly those of Inferior Vena Cava (IVC). In this report we describe an extremely
      rare anatomical entity, where the IVC is formed by the union of the right common
      iliac vein and the left internal iliac vein. This is associated with a parallel
      venous channel which is the upward continuation of the left external iliac vein,
      which finally drains into the IVC at the level of renal veins. Awareness of such
      unusual variation of abdominal venous channels is helpful during retroperitoneal
      and laparoscopic surgeries of the abdomen, in staging of abdominal neoplasm, in
      radiological interpretation as well as therapeutic intervention in cases of
      recurrent pulmonary embolism.

PMID- 21717052
TI  - [High digoxin serum levels in an elderly patient for the endogenous digoxin-like
      immunoreactive substances. A case report].
AB  - Digoxin is typically prescribed in the treatment of heart failure. Its limited
      therapeutic range requires systematic monitoring of plasmatic concentration
      through immunoreactive tests. Laboratory results, however, can be altered by the
      presence of digoxin-like immunoreactive factors (DLIF) which are released in all
      clinical conditions involving volemic expansion. CASE REPORT: An 86-year-old
      woman arrived in emergency with severe dyspnoea, atrial flutter and a medical
      history of ischemic cardiopathy. The patient was treated with ACE inhibitor,
      furosemide, spironolactone and digoxin. The first lab test for digoxin showed
      levels of digoxin of 7.05 ng/ml. Although the patient did not show any clinical
      evidence of digital intoxication nor was she treated with drugs which might
      interfere with digoxin kinetics and even if she had markers of renal function
      within clinical limits, digoxin was suspended and a treatment was initiated with
      0.9% NaCl solution and furosemide. The second lab test showed levels of digoxin
      of 8.38 ng/ml. A possible interference of DLIF with immunoreactive tests was
      therefore assumed. MATERIALS AND METHODS: The patient's serum was ultrafiltered
      and centrifugated to remove possible DLIF; subsequently, the measurement of
      digoxin levels was repeated. As a result, the digoxin level decreased to 0.25
      ng/ml. CONCLUSIONS: DLIF increase in several diseases, including heart failure,
      end-stage renal disease, pre-eclampsy and acromegaly. High digoxin levels in a
      patient who does not show any symptoms of digital intoxication should lead to
      suspect the presence of these factors and to preventively determine DLIF in serum
      so as not to incur the risk of suspending an important treatment like digoxin in
      heart failure.

PMID- 21717053
TI  - An unusual bifid origin of 1st lumbrical muscle of hand: anatomical and clinical
      perspectives.
AB  - Lumbrical muscles are pivotal in execution of fine skillful movements of the
      hand. Anomalies in their morphology are not uncommon. We report an exceptional
      bifid origin of first lumbrical muscle of the left upper limb, discovered
      incidentally in gross anatomy dissection class. The 1st lumbrical was observed to
      comprise of two heads, the accessory one arising from the tendon of flexor
      digitorum superficialis of the index finger and the other main belly taking
      origin as usual from flexor digitorum profundus. The two heads joined to form a
      common muscle belly and were inserted normally in the dorsal digital expansion.
      The report highlights the surgical and phylogenetic significance of such
      variation. Additionally, notification of such muscular variants assumes
      importance in the event of surgical interventions in this region. Moreover, the
      anomalous origin, length and volume of the first lumbrical are important
      parameters for the outcome of operations on the carpal tunnel.

PMID- 21717054
TI  - New perspectives: role of Sunitinib in breast cancer.
AB  - Sunitinib malate (SU11248) is a multitarget oral tyrosine kinase receptor (RTKs)
      inhibitor which was approved by FDA in renal cells carcinoma (RCC) and imatinib
      resistant or imatinib-intollerant gastro-intestinal stromal tumour (GIST).
      Sunitinib is able to inhibit RTKs such as receptors for platelet-derived growth
      factor (PDGF-Ralpha and beta) and for vascular endothelial growth factor
      (VEGFRs). It is able to inhibit KIT receptor, colony stimulating factor type 1
      receptor (CSF-1R), glial cell line neutrophic factor receptor (RET), fms-like
      tyrosine kinase receptor-3 (FLT-3 or CD135), signal transducer and activator of
      transcription 3 (STAT3) and AKT (protein kinase B) in tumour cells. Many
      Sunitinib targets play important roles in growth and survival of human breast
      cancer (BC). The "rationale" of Sunitinib in BC (with or without others
      antiagiogenetic therapy) is its ability to block simultaneously intracellular
      portion of RTKs inhibiting many downstream signals. We overviewed the most
      relevant studies concerning Sunitinib in metastatic BC.

PMID- 21717055
TI  - Molecular characterization of three heat shock protein 70 genes and their
      expression profiles under thermal stress in the citrus red mite.
AB  - Three heat shock protein 70 family transcripts, named PcHsp70-1, PcHsp70-2 and
      PcHsp70-3, were isolated from the citrus red mite, Panonychus citri. PcHsp70-1,
      PcHsp70-2, and PcHsp70-3 contained an open reading frame of 1977, 1968, and 2028
      nucleotides that encoded 658, 655 and 675 amino acid residues, respectively.
      Comparison of deduced amino acid sequences of PcHsp70-1 and PcHsp70-2 showed
      86.34% identity, while the amino acid sequence of PcHsp70-3 was only 57.39 and
      58.75% identical to that of PcHsp70-1 and PcHsp70-2, respectively. Sequences and
      phylogenetic analyses suggested that PcHsp70-1 and PcHsp70-2 were cytosolic Hsps,
      whereas PcHsp70-3 was located in ER (endoplasmic reticulum). To accurately
      validate mRNA expression profiles of the three Hsp70s under thermal stress
      conditions, seven housekeeping genes were evaluated. Alpha-tubulin and RpII were
      selected as optimal endogenous references for cold shock and heat shock
      conditions, respectively. Real-time quantitative RT-PCR revealed that only the
      mRNA expression of PcHsp70-2 was up-regulated under heat shocks, and all of the
      three Hsp70s were constitutively expressed under cold shocks. The results suggest
      that the three Hsp70s were more critical to coping with heat than cold shocks.

PMID- 21717056
TI  - Over-expression in the nucleotide-binding site-leucine rich repeat gene DEPG1
      increases susceptibility to bacterial leaf streak disease in transgenic rice
      plants.
AB  - Bacterial leaf streak of rice (BLS) caused by Xanthomonas oryzae pv. oryzicola
      (Xoc) is a widely-spread disease in the main rice-producing areas of the world.
      Investigating the genes that play roles in rice-Xoc interactions helps us to
      understand the defense signaling pathway in rice. Here we report a differentially
      expressed protein gene (DEPG1), which regulates susceptibility to BLS. DEPG1 is a
      nucleotide-binding site (NBS)-leucine rich repeat (LRR) gene, and the deduced
      protein sequence of DEPG1 has approximately 64% identity with that of the disease
      resistance gene Pi37. Phylogenetic analysis of DEPG1 and the 18 characterized NBS
      LRR genes revealed that DEPG1 is more closely related to Pi37. DEPG1 protein is
      located to the cytoplasm, which was confirmed by transient expression of DEPG1
      GFP (green fluorescent protein) fusion construct in onion epidermal cells. Semi
      quantitative PCR assays showed that DEPG1 is widely expressed in rice, and is
      preferentially expressed in internodes, leaf blades, leaf sheaths and flag
      leaves. Observation of cross sections of leaves from the transgenic plants with a
      DEPG1-promoter::glucuronidase (GUS) fusion gene revealed that DEPG1 is also
      highly expressed in mesophyll tissues where Xoc mainly colonizes. Additionally,
      Xoc negatively regulates expression of DEPG1 at the early stage of the pathogen
      infection, and so do the three defense-signal compounds including salicylic acid
      (SA), methyl jasmonate (MeJA) and 1-aminocyclopropane-1-carboxylic-acid (ACC).
      Transgenic rice plants overexpressing DEPG1 exhibit enhanced susceptibility to
      Xoc compared to the wild-type controls. Moreover, enhanced susceptibility to Xoc
      may be mediated by inhibition of the expression of some SA biosynthesis-related
      genes and pathogenesis-related genes that may contribute to the disease
      resistance. Taken together, DEPG1 plays roles in the interactions between rice
      and BLS pathogen Xoc.

PMID- 21717057
TI  - Liver dominant expression of fatty acid synthase (FAS) gene in two chicken breeds
      during intramuscular-fat development.
AB  - Fatty acid synthase (FAS) is a key enzyme of lipogenesis. In this study, the FAS
      mRNA expression patterns were examined in three fat related tissues (liver,
      breast and thigh) at different developmental stages in two chicken breeds
      (Beijing-You, BJY and Arbor Acres broiler, AA). Results of the Real time-qPCR
      showed that the expression of FAS mRNA level in liver was significantly higher (P
      < 0.01) than that in breast and thigh in both two chicken breeds. Significant
      differences of FAS mRNA expression in liver were found between BJY and AA
      chickens during different developmental stages. After the contents of
      intramuscular-fat (IMF) and the liver fat were measured, the correlation analysis
      was performed. In liver, the FAS mRNA level was highly correlated with hepatic
      fat content (r = 0.891, P < 0.01 for BJY; r = 0.901, P < 0.01 for AA). On the
      contrary, the FAS expression level in both breast and thigh tissues were
      relatively low, stable and there was no correlation between the FAS mRNA level
      and IMF content in breast and thigh tissues of each breed. The results here can
      contribute to the knowledge on the developmental expression pattern of FAS mRNA
      and facilitate the further research on the molecular mechanism underlying IMF
      deposition in chicken.

PMID- 21717058
TI  - Update analysis of studies on the MMP-9 -1562 C>T polymorphism and cancer risk.
AB  - Polymorphisms in the matrix metalloproteinase (MMP) gene have been hypothesized
      to be functional and may contribute to genetic susceptibility to cancers. The
      common sequence variation in MMP-9 -1562 C>T (rs3918242), has been involved in
      cancer risk. However, results of the related published studies were somewhat
      controversial and underpowered in general. To clarify the role of MMP-9 -1562 C>T
      genotype in global cancer, we performed a meta-analysis of all the available
      published studies involving 4,124 cancer patients and 4,728 control subjects. The
      overall results indicated that there was no major association of the variant on
      cancer risk. However, stratified analysis by cancer type showed that the MMP-9 
      1562 C>T polymorphism has a lower risk in colorectal cancer (OR = 0.80, 95%CI =
      0.66-0.96, P (heterogeneity) = 0.391) and lung cancer (OR = 0.70, 95%CI = 0.51
      0.96, P (heterogeneity) = 0.959) by allelic contrast. Furthermore, association of
      the MMP-9 -1562 C>T polymorphism and cancer risk was also observed in hospital
      based studies under the dominant genetic model (OR = 0.87, 95%CI = 0.78-0.97, P
      (heterogeneity) = 0.355), allelic contrast (OR = 0.85, 95%CI = 0.75-0.96, P
      (heterogeneity) = 0.271) and heterozygote comparison (OR = 0.89, 95%CI = 0.79
      0.99, P (heterogeneity) = 0.402). This pooled analysis showed evidence that the
      MMP-9 -1562 C>T polymorphism may decrease both the colorectal and lung cancer
      risk. Further prospective studies with larger numbers of participants worldwide
      are required to evaluate the association in more detail.

PMID- 21717059
TI  - Different genetic patterns in avian Toll-like receptor (TLR)5 genes.
AB  - Toll-like receptors (TLRs) mediate immune response via recognition of pathogen
      associated molecular patterns (PAMPs), thus play important roles in host defense.
      Polymorphisms of TLR5 may affect their recognition of bacterial flagellin,
      leading to varied host resistance to pathogenic infections. Here, we cloned TLR5
      genes from Common Pheasant, Guinea fowl and 9 Chicken breeds and analyzed their
      sequences. The open reading frames of TLR5 were sequenced. Amino acid analysis
      indicated that TLR5 from Chicken breeds shared 99.4-99.9% homology. The amino
      acid homology of TLR5 ranged from 92.1 to 92.5% between Chickens and Guinea fowl,
      95.7-96.1% between Chickens and Turkey, 94.3-94.7% between Chickens and Common
      Pheasant, and 79.9-80.1% between Chickens and Zebra-finch. Different genetic
      patterns were determined among Chickens, Common Pheasant, Guinea fowl, Turkey and
      Zebra-finch. It was found that there were 92 amino acid polymorphic sites, among
      which 5 sites in chicken TLR5, 63 sites in Guinea fowl TLR5 and 44 sites in
      Common Pheasant TLR5. Our data indicate that the positive Darwinian selection
      occurred in avian TLR5 genes since frequency of non-synonymous (d ( N )) >
      frequency of synonymous (d ( S )). These results also demonstrate that avian TLR5
      genes are polymorphic among avian breeds, suggesting a varied resistance among
      breeds of avian. This information might be of help to improve the health of avian
      by breeding and vaccination.

PMID- 21717060
TI  - Diversity of bacterial communities related to the nitrogen cycle in a coastal
      tropical bay.
AB  - A culture-independent molecular phylogenetic analysis was carried out to study
      for the first time the diversity of bacterial ammonia monooxygenase subunit A
      (amoA) and nitrogenase reductase subunit H (nifH) genes from Urca inlet at
      Guanabara Bay in Rio de Janeiro, Brazil. Most bacterial amoA and nifH sequences
      exhibited identities of less than 95% to those in the GenBank database revealing
      that novel ammonia-oxidizing bacteria and nitrogen-fixing microorganisms may
      exist in this tropical marine environment. The observation of a large number of
      clones related to uncultured bacteria also indicates the necessity to describe
      these microorganisms and to develop new cultivation methodologies.

PMID- 21717061
TI  - The use of microsatellite polymorphism in genetic mapping of the ostrich
      (Struthio camelus).
AB  - The aim of this study was to determine microsatellite polymorphism in ostriches
      and using it in creation the genetic map of the ostrich. The polymorphism
      analysis covered 30 microsatellite markers characteristic of ostrich, for the CAU
      (China Agricultural University) group. The material consisted of 150 ostriches
      (Struthio camelus). The 30 microsatellite loci was examined and a total of 343
      alleles was identified. The number of alleles at a single locus ranged from 5 at
      locus CAU78 to 34 at locus CAU85. The values for the observed heterozygosity H(o)
      ranged from 0.467 (locus CAU78) to 0.993 (locus CAU16), whereas for the expected
      heterozygosity H(e)--from 0.510 (locus CAU78) to 0.953 (locus CAU85). Analyzing
      the individual loci, the highest PIC value, more than 0.7 was observed for: loci
      CAU85 (0.932), CAU64 (0.861) and CAU32, 75 (0.852), respectively. It should be
      noted, that the microsatellite markers used in our study were very polymorphic as
      evidenced by the large number of detected alleles and high rates of
      heterozygosity, PIC and PE as well. The analysed microsatellite markers may be
      used in genetic linkage mapping of ostrich, the construction of a comparative
      genetic map with other ratites, such as emu and rhea, and population genetics
      studies or phylogenetic studies of these birds.

PMID- 21717062
TI  - Preface: Happy 10th anniversary!

PMID- 21717063
TI  - The CSPG4-specific monoclonal antibody enhances and prolongs the effects of the
      BRAF inhibitor in melanoma cells.
AB  - PLX4032 is a BRAF-selective inhibitor shown to be efficacious in the treatment of
      melanomas presenting with the BRAF(V600E) mutation. However, favorable responses
      to treatment are short-lived, and complete remission is rarely observed.
      Therefore, it is important to identify novel therapies designed to enhance
      treatment responses and to increase the longevity of initial response to BRAF
      inhibitors. To this end, we characterized the effects of the 225.28 chondroitin
      sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibody (mAb) capable of
      blocking multiple signaling pathways important to cell growth, migration, and
      survival. Addition of 225.28 to the treatment regimen enhanced the in vitro
      response magnitude and the duration efficacy of PLX4032 in treating CSPG4(+),
      BRAF(V600E) melanoma cells (melanoma(BRAF(V600E)/CSPG4+) cells). Data presented
      in this report demonstrated that (1) treatments comprised of PLX4032 and mAb
      225.28 were more effective at inhibiting melanoma(BRAF(V600E)/CSPG4+) cell growth
      than either agent alone, (2) mAb 225.28 prevented/delayed the development of
      resistance in melanoma(BRAF(V600E)/CSPG4+) cells to PLX4032, and (3) the
      mechanism of action of the combination therapy caused a down-regulation in
      multiple signaling pathways. This study provides a foundation for future
      investigations designed to improve BRAF inhibitor effectiveness in vitro and in
      vivo for treating melanoma(BRAF(V600E)/CSPG4+) cells in combination with a CSPG4
      specific mAb.

PMID- 21717064
TI  - Natural killer (NK): dendritic cell (DC) cross talk induced by therapeutic
      monoclonal antibody triggers tumor antigen-specific T cell immunity.
AB  - Tumor antigen (TA)-targeted monoclonal antibodies (mAb), trastuzumab, cetuximab,
      panitumumab, and rituximab, have been among the most successful new therapies in
      the present generation. Clinical activity is observed as a single agent, or in
      combination with radiotherapy or chemotherapy, against metastatic colorectal
      cancer, head and neck cancer, breast cancer, and follicular lymphoma. However,
      the activity is seen only in a minority of patients. Thus, an intense need exists
      to define the mechanism of action of these immunoactive mAb. Here, we discuss
      some of the likely immunological events that occur in treated patients: antibody
      dependent cellular cytotoxicity (ADCC), cross talk among immune cells including
      NK cells and dendritic cells (DCs), and generation of TA-specific T lymphocyte
      responses. We present evidence supporting the induction of "NK:DC cross talk,"
      leading to priming of TA-specific cellular immunity. These observations show that
      mAb-mediated NK cell activation can be greatly enhanced by the action of
      stimulatory cytokines and surface molecules on maturing DC and that NK:DC
      interaction facilitates the recruitment of both NK cells and DC to the tumor
      site(s). The cooperative, reciprocal stimulatory activity of both NK cells and DC
      can modulate both the innate immune response in the local tumor microenvironment
      and the adaptive immune response in secondary lymphoid organs. These events
      likely contribute to clinical activity, as well as provide a potential biomarker
      of response to mAb therapy.

PMID- 21717065
TI  - Lung myeloid-derived suppressor cells and regulation of inflammation.
AB  - Myeloid-derived suppressor cells (MDSCs) have been investigated largely in the
      context of tumor progression. In contrast to the negative connotation of MDSCs in
      cancer immunity, our laboratory has recently reported on the development and role
      of pulmonary MDSC-like cells (CD11b(+)Gr1(int)F4/80(+)) in the regulation of
      allergic airway inflammation. These regulatory cells were expanded in a
      TLR4/MyD88-dependent manner and were both phenotypically and morphologically
      similar to those described in the tumor microenvironment. Although bacterial
      lipopolysaccharide (LPS) was initially described as an adjuvant in the
      development of allergic inflammation, subsequent studies showed that this is true
      only at relatively low doses of LPS. A high dose of LPS was shown to actually
      suppress eosinophilic airway inflammation. In our efforts to understand the
      mechanism underlying LPS-mediated suppression of allergic airway disease, we
      recently showed that LPS induces MDSC-like cells in the lung tissue in a dose
      dependent manner, with increased accumulation of the cells at high doses of LPS.
      In contrast to lung dendritic cells (DCs), the MDSC-like cells did not traffic to
      the lung-draining lymph nodes, allowing them to act in a dominant fashion over
      DCs in the regulation of Th2 responses. The MDSC-like cells were found to blunt
      the ability of the lung DCs to upregulate GATA-3 or to promote STAT5 activation
      in primed Th2 cells, both transcription factors having critical roles in Th2
      effector function. Thus, a complete understanding of the generation and
      regulation of the lung MDSCs would provide novel options for therapeutic
      interventions.

PMID- 21717066
TI  - Latent tuberculosis: what the host "sees"?
AB  - Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), is
      the most successful pathogen of mankind and remains a major threat to global
      health as the leading cause of death due to a bacterial pathogen. Yet 90-95% of
      those who are infected with MTB remain otherwise healthy. These people are
      classified as "latently infected," but remain a reservoir from which active TB
      cases will continue to develop ("reactivation tuberculosis"). Latent infection is
      defined by the absence of clinical symptoms of TB in addition to a delayed
      hypersensitivity reaction to the purified protein derivative of MTB used in
      tuberculin skin test or a T-cell response to MTB-specific antigens. In the
      absence of reliable control measures for tuberculosis, understanding latent MTB
      infection and subsequent reactivation is a research priority. This review aims to
      summarize the recent findings in human and non-human primate models of
      tuberculosis that have led to new concepts of latent tuberculosis.

PMID- 21717067
TI  - Role of TNF superfamily ligands in innate immunity.
AB  - Natural killer (NK) cells and dendritic cells (DCs) are essential effector cells
      of the innate immune system that rapidly recognize and eliminate microbial
      pathogens and abnormal cells, and induce and regulate adaptive immune functions.
      While NK cells express perforin and granzymes in the lysosomal granules and
      transmembrane tumor necrosis factor superfamily ligands (tmTNFSFL) on the plasma
      membrane, DCs express only tmTNFSFL on the plasma membrane. Perforin and
      granzymes are cytolytic molecules, which NK cells use to mediate a
      secretory/necrotic killing mechanism against rare leukemia cell targets. TNFSFL
      are pleiotropic transmembrane molecules, which can mediate a variety of important
      functions such as apoptosis, development of peripheral lymphoid tissues,
      inflammation and regulation of immune functions. Using tmTNFSFL, NK cells and DCs
      mediate a cell contact-dependent non-secretory apoptotic cytotoxic mechanism
      against virtually all types of cancer cells, and cross talk that leads to
      polarization and reciprocal stimulation and amplification of Th1 type cytokines
      secreted by NK cells and DCs. In this paper, we review and discuss the supporting
      evidence of the non-secretory, tmTNFSFL-mediated innate mechanisms of NK cells
      and DCs, their roles in anticancer immune defense and potential of their
      modulation and use in prevention and treatment of cancer.

PMID- 21717068
TI  - T-cell-mediated tumor immune surveillance and expression of B7 co-inhibitory
      molecules in cancers of the upper gastrointestinal tract.
AB  - Tumorigenesis can induce adaptive T-cell-mediated immune responses against
      malignant cells. Such cellular immune responses are actively suppressed by cancer
      cells via mechanisms of immune tolerance. We studied T-cell responses against
      tumor growth by examining tumor-infiltrating lymphocytes (TILs) in upper
      gastrointestinal (GI) cancers. The number of T-bet(+) TILs correlates with better
      survival of esophageal cancer patients. Using well-defined mouse models, we have
      further shown that T-bet and Eomes are both required for the adaptive anti-tumor
      immunity by regulating T-cell trafficking into the tumor tissue and their
      effector functions inside the tumor microenvironment. In order to gain further
      insight into the tumor immune microenvironment in the upper GI cancer, we have
      also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and
      B7-H4 in tissue specimens of esophageal and gastric cancers. These inhibitory B7
      molecules were expressed at high but variable levels by cancer cells. The
      overexpression of these molecules correlates with poor clinicopathological
      parameters and shorter patient survival time. The number of CD3(+) and CD8(+)
      TILs correlates inversely with expression levels of B7-H4 in samples from
      esophageal cancer, supporting a role of active immune suppression by inhibitory
      B7 molecules in the tumor microenvironment. In addition, TILs show functional
      exhaustion and express high levels of PD-1 and Tim-3. We propose that metabolic
      competition mediated by phosphatidylinositol 3-kinases (PI3Ks) characterizes the
      immune suppression within cancer tissues. Future tumor vaccine design should
      combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes
      levels within the tumor microenvironment.

PMID- 21717069
TI  - IL-17 signaling in host defense against Candida albicans.
AB  - The discovery of the Th17 lineage in 2005 triggered a major change in how
      immunity to infectious diseases is viewed. Fungal infections, in particular, have
      long been a relatively understudied area of investigation in terms of the host
      immune response. Candida albicans is a commensal yeast that colonizes mucosal
      sites and skin. In healthy individuals, it is non-pathogenic, but in conditions
      of immune deficiency, this organism can cause a variety of infections associated
      with considerable morbidity. Candida can also cause disseminated infections that
      have a high mortality rate and are a major clinical problem in hospital settings.
      Although immunity to Candida albicans was long considered to be mediated by Th1
      cells, new data in both rodent models and in humans have revealed an essential
      role for the Th17 lineage, and in particular its signature cytokine IL-17.

PMID- 21717070
TI  - Transcriptional and epigenetic regulation of B cell development.
AB  - B cell development starts in the bone marrow where hematopoietic stem cells
      (HSCs) progress through sequential developmental stages, as it differentiates
      into a naive B cell expressing surface immunoglobulin. In the periphery, B cells
      that encounter antigen can further differentiate into antibody-secreting plasma
      cells. In this review, we focus on two factors, E47 and ELL2, which play
      important roles in the regulation of B cell development in the bone marrow and
      differentiation of mature B cells into plasma cells in the periphery,
      respectively. First, E47 activity is required for B cell development in the bone
      marrow. In addition, we have identified a cell-intrinsic role for E47 in
      regulating efficient self-renewal and long-term multilineage bone marrow
      reconstitution potential of HSCs. Second, we explored the role of transcription
      elongation factors in the super elongation complex (SEC), including ELL2 (eleven
      nineteen lysine-rich leukemia factor) in driving poly(A) site choice and plasma
      cell development. We found that elongation factors impel high levels of IgH mRNA
      production and alternative processing at the promoter proximal, secretory
      specific (sec) poly(A) site in plasma cells by enhancing RNA polymerase II
      modifications and downstream events. The sec poly(A) site, essentially hidden in
      B cells, is found by SEC factors in plasma cells.

PMID- 21717072
TI  - Hepatic antigen-presenting cells and regulation of liver transplant outcome.
AB  - In the steady state, hepatic antigen (Ag)-presenting cells (APC) generally dampen
      systemic inflammatory responses to gut-derived Ags. Our studies focus on the role
      of specific liver APC populations, both non-parenchymal cells (dendritic cells
      [DC], Kupffer cells, and hepatic stellate cells [HSC]) and parenchymal cells, in
      the molecular regulation of tissue damage (ischemia and reperfusion [I/R] injury)
      and immunity following liver transplantation. We focus on factors that either
      promote or overwhelm the natural tendency of the liver to suppress
      inflammatory/immune responses. We are also examining molecular mechanisms that
      regulate liver DC maturation and function and that determine their role in the
      control of allogeneic T-cell function and the fate of the transplanted liver. Our
      studies are also aimed at elucidating mechanisms by which HSC regulate DC and T
      cell function. These investigations may provide new targets for therapeutic
      intervention in liver inflammation.

PMID- 21717071
TI  - Dendritic cells in cancer immunotherapy: vaccines or autologous transplants?
AB  - Dendritic cells (DCs) are the most powerful immunostimulatory cells specialized
      in the induction and regulation of immune responses. Their properties and the
      feasibility of their large-scale ex vivo generation led to the application of ex
      vivo-educated DCs to bypass the dysfunction of endogenous DCs in cancer patients
      and to induce therapeutic anti-cancer immunity. While multiple paradigms of
      therapeutic application of DCs reflect their consideration as cancer "vaccines",
      numerous features of DC-based vaccination resemble those of autologous
      transplants, resulting in challenges and opportunities that distinguish them from
      classical vaccines. In addition to the functional heterogeneity of DC subsets and
      plasticity of the individual DC types, the unique features of DCs are the kinetic
      character of their function, limited functional stability, and the possibility to
      imprint in maturing DCs distinct functions relevant for the induction of
      effective cancer immunity, such as the induction of different effector functions
      or different homing properties of tumor-specific T cells (delivery of "signal 3"
      and "signal 4"). These considerations highlight the importance of the application
      of optimized, potentially patient-specific conditions of ex vivo culture of DCs
      and their delivery, with the logistic and regulatory implications shared with
      transplantation and other surgical procedures.

PMID- 21717073
TI  - CD8+ T cells in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a progressive and highly debilitating autoimmune
      disorder characterized by inflammation, fibrosis, and vascular damage of the
      connective tissue. T cell-derived cytokines have been implicated in the induction
      of fibrosis. We found that high levels of the profibrotic type-2 cytokine IL-13
      are produced by peripheral blood effector CD8(+) T cells from SSc patients
      compared to normal controls. This abnormality correlates with increased
      expression of the transcription factor GATA-3 and the extent of skin fibrosis.
      Together, the data provide new insights into SSc pathogenesis and identify a
      specific T cell phenotype that can be used as a biomarker of immune dysfunction
      in patients with SSc and as a novel therapeutic target for this currently
      incurable disease.

PMID- 21717074
TI  - A role for the heat shock protein-CD91 axis in the initiation of immune responses
      to tumors.
AB  - For over 100 years, it has been established that tumor-specific immune responses
      can frequently be detected in the tumor-bearing host. Whether or not these immune
      responses are capable of controlling the growth of the tumor is influenced by
      many factors. However, the mechanism by which the immune responses are initiated
      in the first place has remained a dilemma. In this chapter, we present evidence
      that heat shock protein-peptide complexes released by tumor cells are the entity
      responsible for initiating the immune responses. Interaction of the extracellular
      HSP with its receptor CD91 is necessary for priming the immune response. We
      propose that the disruption of the HSP-CD91 interaction may be an active
      mechanism by which tumors prevent the generation of immune responses against it.

PMID- 21717075
TI  - Dissecting the role of dendritic cells in simian immunodeficiency virus infection
      and AIDS.
AB  - Human immunodeficiency virus (HIV) infection is associated with the loss of the
      two principal types of dendritic cell (DC), myeloid DC (mDC) and plasmacytoid DC
      (pDC), but the mechanism of this loss and its relationship to AIDS pathogenesis
      remain ill-defined. The nonhuman primate is a powerful model to dissect this
      response for several reasons. Both DC subsets have been well characterized in
      nonhuman primates and shown to have strikingly similar phenotypic and functional
      characteristics to their counterparts in the human. Moreover, decline of mDC and
      pDC occurs in rhesus macaques with end-stage simian immunodeficiency virus (SIV)
      infection, the model of HIV infection in humans. In this brief review, we discuss
      what is known about DC subsets in pathogenic and nonpathogenic nonhuman primate
      models of HIV infection and highlight the advances and controversies that
      currently exist in the field.

PMID- 21717076
TI  - Role of neurokinin-1 receptor in the initiation and maintenance of skin chronic
      inflammatory diseases.
AB  - To fulfill its immunologic functions, the skin is richly populated with dendritic
      cells (DCs), the most potent professional Ag-processing and Ag-presenting cells
      of the immune system. The immune-stimulatory and tolerogenic functions of skin
      DCs are regulated by the immune and neuroendocrine systems. Pro-inflammatory
      neuropeptides like substance P and calcitonin gene-related peptide secreted by
      cutaneous Adelta and C nerve fibers are the main initiators of neuro-inflammatory
      responses in the skin. Conversely, anti-inflammatory neuropeptides like the
      products of cleavage of proopiomelanocortin (alpha-melanocyte-stimulating hormone
      and adrenocorticotropic hormone) negatively regulate immune responses in the
      skin. Likewise, the control of immune responses against stimuli applied to the
      skin depends on the balance between the release and neutralization of pro
      inflammatory and anti-inflammatory neuropeptides, a matter that has been somehow
      overlooked by the immunology field until recently.

PMID- 21717077
TI  - Pneumocystis infection and the pathogenesis of chronic obstructive pulmonary
      disease.
AB  - With increases in the immunocompromised patient population and aging of the HIV+
      population, the risk of serious fungal infections and their complications will
      continue to rise. In these populations, infection with the fungal opportunistic
      pathogen Pneumocystis jirovecii remains a leading cause of morbidity and
      mortality. Infection with Pneumocystis (Pc) has been shown to be associated with
      the development of chronic obstructive pulmonary disease (COPD) in human subjects
      with and without HIV infection and in non-human primate models of HIV infection.
      In human studies and in a primate model of HIV/Pc co-infection, we have shown
      that antibody response to the Pc protein, kexin (KEX1), correlates with
      protection from colonization, Pc pneumonia, and COPD. These findings support the
      hypothesis that immunity to KEX1 may be critical to controlling Pc colonization
      and preventing or slowing development of COPD.

PMID- 21717078
TI  - Dendritic cells and the maintenance of self-tolerance.
AB  - Dendritic cells (DC) play important roles in the initiation of immune responses
      and in the maintenance of self-tolerance. We have been studying the role of DC in
      the pathogenesis of type 1 diabetes and exploring the ability of specific DC
      subsets to prevent diabetes in non-obese diabetic (NOD) mice. DC presenting low
      doses of antigen are capable of inducing and expanding T-regulatory (Treg) cells
      that have potent suppressive function. We review here our recent findings in this
      area and highlight the ability of semi-mature therapeutic DC to induce Treg
      expansion in the absence of exogenous antigen. We discuss how the presentation of
      endogenous self-antigen by DC may represent a natural mechanism for peripheral
      self-tolerance that can be harnessed to prevent autoimmunity.

PMID- 21717079
TI  - Regulation of NF-kappaB induction by TCR/CD28.
AB  - NF-kappaB family transcription factors are a common downstream target for
      inducible transcription mediated by many different cell-surface receptors,
      especially those receptors involved in inflammation and adaptive immunity. It is
      now clear that different classes of receptors employ different proximal signaling
      strategies to activate the common NF-kappaB signaling components, such as the IKK
      complex. For antigen receptors expressed by T and B cells, this pathway requires
      a complex of proteins including the proteins Carma1, Bcl10, and Malt1. Here, we
      discuss some of what is known about regulation of these proteins downstream of
      TCR/CD3 and co-stimulatory CD28 signaling. We also discuss another unique aspect
      of TCR-mediated NF-kappaB activation, i.e., the spatial restriction imposed on
      signaling events by the formation of the immunological synapse between a T cell
      and antigen-presenting cell presenting specific peptide/MHC.

PMID- 21717080
TI  - A multivalent vaccine for type 1 diabetes skews T cell subsets to Th2 phenotype
      in NOD mice.
AB  - Previous studies by our group, using an experimental autoimmune thyroiditis (EAT)
      model in Strain 13 inbred guinea pigs, resulted in T cell-mediated delayed
      hypersensitivity; however, autoantibodies proved not to be cytotoxic to thyroid
      epithelial cells in the presence or absence of complement proteins. Albeit, T
      cell-mediated lymphocyte cytotoxicity began to diminish sharply concomitantly
      with increasing titers of circulating autoantibodies, indicating a skewing of the
      self-reactive response and amelioration of the EAT. Furthermore, immunization of
      guinea pigs with thyroglobulin in incomplete Freund's adjuvant (IFA) generated a
      high titer of antithyroglobulin antibodies and proved to inhibit thyroiditis.
      These observations indicated that the shift in the immune response from Th1 to
      Th2 and the production of antibodies were likely responsible for ameliorating
      EAT. Based upon these results, we extrapolated our studies to design a
      multivalent vaccine, which shows promise in preventing/reversing T1D in NOD mice.
      A small pilot study was conducted in which a total of 34 mice, 20 non-immunized
      controls and 14 immunized with syngeneic islet lysate, were monitored for mean
      day to diabetes for a total of 28 weeks. Immunization of NOD animals with
      syngeneic islet lysates resulted in a significant delay in diabetes onset (P <
      0.001) as compared to non-immunized controls. To further assess the vaccine's
      efficacy, robustness, and delay of disease, a large-scale experiment was
      conducted and monitored for 32 weeks using 106 mice, 64 non-immunized controls
      and 42 immunized with syngeneic islet lysate. At the end of the study, 90% of the
      non-immunized group developed diabetes, while less than 25% of the immunized
      group became diabetic (P < 0.0001). The protective effect, as a result of
      vaccination, correlated with an increase in the levels of IL-10 and IL-4
      cytokines as well as a skewing to Th2-dependent isotype antibodies in serum.
      Strikingly, adoptive transfer of spleen cells from immunized animals into
      NOD.scid recipients provided protection against transfer of diabetes by
      diabetogenic spleen cells. The results of this study provide evidence that
      vaccination with islet lysate leads to a Th2-dependent skewing of the immune
      response to islet beta cells as a possible mechanism of protection. This strategy
      may be implemented as a possible vaccination protocol for arresting and/or
      preventing T1D in patients.

PMID- 21717081
TI  - Importance of MUC1 and spontaneous mouse tumor models for understanding the
      immunobiology of human adenocarcinomas.
AB  - Many important aspects of cancer biology, such as cancer initiation, progression,
      and metastasis, have been studied in animal models, mostly mice. As long as
      cancer was considered primarily a genetic disease, the study of transplantable
      mouse tumors, or even human tumor xenografts in immunocompromised mice, appeared
      to suffice. Many important genetic events that lead to transformation and in vivo
      tumor growth were elucidated. However, many even more important factors that
      determine whether or not the genetic potential of a tumor cell will be realized,
      such as the host response to the tumor and the tumor microenvironment that
      influences this response over a long period of time of tumor development,
      remained untested and unappreciated. This is slowly changing with the advent of
      molecular techniques that have spurred efforts to engineer better mouse models of
      human tumors. In this review, we show results of our efforts to combine a genetic
      mouse model of spontaneous human adenocarcinomas based on a Kras mutation, with
      an important human molecule MUC1 that is abnormally expressed on human
      adenocarcinomas, promoting oncogenesis, proinflammatory tumor microenvironment,
      and immunosurveillance.

PMID- 21717082
TI  - Targeting myeloid regulatory cells in cancer by chemotherapeutic agents.
AB  - Recent findings in humans and numerous experimental models provide evidence of
      the important role of immune regulatory cells in cancer and various diseases.
      "Myeloid regulatory cells" (MRC) include myeloid-derived suppressor cells,
      regulatory dendritic cells, regulatory macrophages, and subsets of granulocytes
      that expand during pathologic conditions and that have the ability to suppress
      cellular immunity. A decrease in MRC population and/or activity has been shown to
      have positive immune-potentiating effects. Several clinical trials have thus been
      initiated with the goal of manipulating the expansion or activation of these
      cells and thereby improving patient immune responses. New data from our own and
      other laboratories recently revealed that ultralow noncytotoxic doses of certain
      chemotherapeutic drugs could up-regulate antitumor immunity by modulating the
      formation, differentiation, and/or function of MRC. This new phenomenon, termed
      "chemomodulation," allows for the regulation of the tumor microenvironment
      without the undesirable toxic effects associated with conventional chemotherapy.
      However, further studies are required before this new targeted therapy can find
      its way to patients with cancer.

PMID- 21717083
TI  - Macrophage responses to bacterial toxins: a balance between activation and
      suppression.
AB  - Toxins secreted by bacteria can impact the host in a number of different ways. In
      some infections, toxins play a crucial and central role in pathogenesis (i.e.,
      anthrax), while in other bacterial infections, the role of toxins is less
      understood. The cholesterol-dependent cytolysins (CDCs), of which streptolysin O
      is a prototype, are a class of pore-forming toxins produced by many gram-positive
      bacteria and have only been studied in a few experimental infection models. Our
      laboratory has demonstrated that CDCs have effects on macrophages that are both
      pro- and anti-inflammatory. Here, we review evidence that CDCs promote
      inflammation by driving secretion of IL-1beta and HMGB-1 from macrophages in a
      NLRP3-dependent manner, while also causing shedding of membrane microvesicles
      from cells that can interact with macrophages and inhibit TNF-alpha release. CDCs
      thus impact macrophage function in ways that may be both beneficial and
      detrimental to the host.

PMID- 21717084
TI  - Immunotherapeutic potential of oncolytic vaccinia virus.
AB  - There has recently been resurgence in interest for the use of replication
      selective (oncolytic) viruses for the treatment of cancers. This has been fueled
      by positive clinical data and the promise provided by next-generation vectors
      that are better targeted and display enhanced therapeutic potential. One factor
      that has led to more effective oncolytic vectors has been a greater appreciation
      of their immunotherapeutic potential. This is especially true for strains of
      vaccinia virus, where the capability for rapid and destructive spread through a
      target tissue makes this virus the ideal backbone for an oncolytic agent, while
      its known ability to produce a potent immune response makes it a powerful
      immunotherapeutic. Approaches to developing next-generation vectors that are
      capable of effectively harnessing both of these mechanisms of action are
      discussed here.

PMID- 21717086
TI  - Studies on the protective effects of betaine against oxidative damage during
      experimentally induced restraint stress in Wistar albino rats.
AB  - Stress can be defined as physical and psychological modifications that disrupt
      the homeostasis and the balance of organisms. Stress is known as one of the most
      important reasons of several diseases. In the present study, the anti-stress
      effect of betaine was evaluated with reference to its antioxidant property.
      Wistar albino rats were divided into four groups such as control, betaine,
      restraint stress (6 h/day for 30 days), and betaine + restraint stress. The
      oxidative damage was assessed by measuring the protein and corticosterone in
      plasma, lipid peroxidation, non-enzymic (reduced glutathione), and enzymic
      antioxidants (glutathione peroxidase, glutathione-S-transferase, catalase, and
      superoxide dismutase) in the lymphoid organs of thymus and spleen. Followed by
      the induction of restraint stress, the non-enzymic and enzymic antioxidants were
      significantly decreased with concomitant increase observed in the levels of
      corticosterone and lipid peroxidation. Oral pretreatment with betaine (250 mg/kg
      body weight daily for a period of 30 days) significantly (P < 0.001) prevented
      the restraint stress-induced alterations in the levels of protein and
      corticosterone in plasma of experimental groups of rats. It counteracted the
      restraint stress-induced lipid peroxidation and maintained the antioxidant
      defense system in the lymphoid tissues at near normal. The findings suggest that
      betaine possesses significant anti-stress activity, which may be due to its
      antioxidant property.

PMID- 21717087
TI  - A cell model to study different degrees of Hsp60 deficiency in HEK293 cells.
AB  - Mitochondrial dysfunction is associated with neurodegenerative diseases and
      mutations in the HSPD1 gene, encoding the mitochondrial Hsp60 chaperone, are the
      causative factors of two neurodegenerative diseases, hereditary spastic
      paraplegia and MitChap60 disease. In cooperation with Hsp10, Hsp60 forms a barrel
      shaped complex, which encloses unfolded polypeptides and provides an environment
      facilitating folding. We have generated an Hsp60 variant with a mutation
      (Asp423Ala) in the ATPase domain and established a stable human embryonic kidney
      (HEK293) cell line allowing tetracycline-controlled expression of this mutant
      variant. We monitored expression of the Hsp60-Asp423Ala variant protein following
      induction and examined its effects on cellular properties. We showed that the
      folding of mitochondrial-targeted green fluorescent protein, a well-known
      substrate protein of Hsp60, was consistently impaired in cells expressing Hsp60
      Asp423Ala. The level of the Hsp60-Asp423Ala variant protein increased over time
      upon induction, cell proliferation stopped after 48-h induction and mitochondrial
      membrane potential decreased in a time-dependent manner. In summary, we have
      established a stable cell line with controllable expression of an Hsp60 variant,
      which allows detailed studies of different degrees of Hsp60 deficiency.

PMID- 21717088
TI  - Antipsychotic property of aqueous and ethanolic extracts of Lonchocarpus
      cyanescens (Schumach and Thonn.) Benth. (Fabaceae) in rodents.
AB  - Lonchocarpus cyanescens (LC) is a medicinal plant commonly used in combination
      with other recipes in the treatment of psychotic disorders in traditional
      medicine. This study was designed to examine whether the aqueous and ethanolic
      extracts of LC possess antipsychotic property in rats. The antipsychotic effects
      of the extracts were assessed using the amphetamine animal model of psychosis in
      rats. The effect of the extracts on spontaneous motor activity was also studied
      in the open field test in mice. The extrapyramidal side effect of catalepsy was
      tested based on the ability of the extracts to alter the duration of akinesia in
      mice placed on a vertical wrapped string. Aqueous and ethanolic extracts of LC
      (25-400 mg/kg, i.p.) significantly (p < 0.05) suppressed stereotyped behaviour
      induced by amphetamine (10.0 mg/kg, i.p.) in rats, which suggest antipsychotic
      activity. The extracts (25-400 mg/kg, i.p.) further produced a significant (p <
      0.05) reduction in spontaneous motor activity of the animals in the open field
      test. However, in contrast to chlorpromazine, a typical antipsychotic, the
      extracts did not induce cataleptic behaviour in the animals. Preliminary
      phytochemical screening showed the presence of alkaloids, anthraquinones, cardiac
      glycosides, cyanogenetic glycosides, flavonoids, saponins, steroids and tannins
      in the leaves of LC. The presence of these secondary metabolites was confirmed by
      thin-layer chromatography. Taken together, these findings suggest that the
      extracts possess phytochemically active constituents with antipsychotic property.
      Thus, this investigation provides evidence that may justify the ethnomedicinal
      applications of Lonchocarpus cyanescens as the major constituent of the recipe
      used for the management of psychosis in Nigeria.

PMID- 21717089
TI  - Protective effect of Pueraria tuberosa DC. embedded biscuit on cisplatin-induced
      nephrotoxicity in mice.
AB  - Recently, the nephroprotective property of Pueraria tuberosa DC. tuber (PT) has
      been reported by our group. Here, PT-embedded biscuits were prepared and tested
      on cisplatin-induced nephrotoxicity in Swiss albino mice. The PT powder was
      characterized by RAPD (random amplified polymorphic DNA) to ascertain its
      authenticity and PT biscuits were prepared in different concentrations (1, 2, or
      4 g of PT powder). These biscuits were given as diet for a total of 10 days, but
      on the 7th day cisplatin injection (8 mg/kg bw, i.p.) was given. On the 10th day
      animals were killed to collect kidneys for assessment of antioxidant status.
      Blood samples were collected on both the 7th and 10th days for assessment of
      liver and kidney functions. In mice, PT biscuit showed significant protection
      against cisplatin-induced nephrotoxicity, but there was a transient rise in
      alanine aminotransferase and aspartate aminotransferase at the dose of 4 g PT
      biscuit. Therefore, it is suggested that PT biscuit might be an effective food
      supplement for cancer patients undergoing cisplatin-chemotherapy. However,
      periodical liver function monitoring is required, especially when PT is used for
      longer periods or at higher doses.

PMID- 21717090
TI  - Studies on chemical fingerprints of Siraitia grosvenorii fruits (Luo Han Guo) by
      HPLC.
AB  - A novel, efficient, and accurate fingerprinting method using high performance
      liquid chromatography-photodiode array detection has been developed and optimized
      for the investigation and demonstration of the variance in chemical properties
      among Siraitia grosvenorii fruits from different origins. The effects of growth
      stages, cultivated varieties, collection locations, and fruit portions of the
      herb on chromatographic fingerprints were examined. Eleven compounds were
      identified on chromatograms by comparing the retention time and UV spectrum of
      each peak separately with those of external references. The results revealed that
      chromatographic fingerprints, combining similarity or hierarchical clustering
      analysis along with reference compounds, could efficiently identify and
      distinguish S. grosvenorii fruits from different sources, which provided helpful
      clues for studying the plants' secondary metabolites and benefitted quality
      control.

PMID- 21717091
TI  - Safety and feasibility of S-1 adjuvant chemotherapy for gastric cancer in elderly
      patients.
AB  - BACKGROUND: The safety and feasibility of administering S-1 adjuvant chemotherapy
      for gastric cancer has not been fully evaluated in elderly patients. METHODS:
      This retrospective study selected patients who underwent curative D2 surgery for
      gastric cancer, were diagnosed with stage II or III disease, and received
      adjuvant S-1 at our institution. Patients were categorized into two groups; non
      elderly patients (age <70 years: group A) and elderly patients (age >=70 years:
      group B). The toxicity and S-1 continuation rates in the two groups were
      compared. RESULTS: A total of 75 patients were evaluated in the study. There were
      no grade 4 toxicities. The incidences of grade 3 hematological and non
      hematological toxicities were <5% in both groups, and the differences were not
      significant. The continuation rate at 6 months was 69% in group A and 70% in
      group B, and this difference was also not significant. CONCLUSIONS: These results
      suggest that S-1 adjuvant chemotherapy for gastric cancer is safe and feasible,
      regardless of the age of the patient; especially for elderly patients who could
      be candidates for clinical trials.

PMID- 21717092
TI  - Gastric linitis plastica: which role for surgical resection?
AB  - BACKGROUND: The role of surgery for gastric linitis plastica (GLP) is questioned.
      This study aimed to analyze our experience in the surgical treatment of GLP with
      specific reference to the resectability rate, prognosis, and mode of recurrence.
      METHODS: Results of surgery were analyzed in 102 patients with GLP. RESULTS: Of
      the 102 patients, 92 underwent surgical exploration, with resection performed in
      60 cases. R2 resection was carried out in 20 patients and R1 in 12 patients,
      while the resection was considered potentially curative (R0) in 28 (27.5%).
      Overall, the median (95% confidence interval [CI]) survival time was 5.7 (3.7
      7.5) months, with none of the patients alive at the end date of the study. For R0
      patients the median (95% CI) survival time was 15.8 (11-20.7) months. The great
      majority of recurrences were intra-abdominal (peritoneal and/or locoregional),
      with a systemic component of the relapse that was rarely observed (5 cases).
      CONCLUSIONS: After primary surgery, GLP showed a poor prognosis without regard to
      the extent or type of resection. The failure of surgical treatment related mainly
      to the peritoneal spread of the disease. Specifically designed multimodality
      treatment protocols should be tested in this setting.

PMID- 21717093
TI  - Sacral neuromodulation for the management of severe constipation: development of
      a constipation treatment protocol.
AB  - BACKGROUND: Constipation is a common multifactorial gastrointestinal symptom with
      quality of life implications. Sacral neuromodulation has been used in the
      management of severe constipation with mixed results. The aim of this study was
      to review our experience of sacral neuromodulation as a treatment for chronic
      constipation and develop a chronic constipation management protocol. METHODS: In
      patients with severe constipation, failure of conservative management including
      biofeedback and rectal irrigation were considered for neuromodulation. Temporary
      stimulation lead was placed in the sacral foramen of eligible patients and pre
      and post stimulation bowel diaries were compared. Patients with >=50% improvement
      in bowel diaries had permanent implant. Patients were followed up at 2 and 4
      weeks, 3, 6, and 12 months, and then yearly with bowel diaries. RESULTS:
      Temporary neuromodulation wires were implanted in 21 patients (20 female).
      Significant bowel diary improvement was seen in 12 (57%) patients (p < 0.01).
      Eleven permanent implants have been performed. Improvement in symptoms was lost
      in one patient. No major side effects were observed. Three patients have had
      reoperations (one wire fracture, one reposition of battery, and one poor initial
      lead placement). Improvements in bowel diaries have been maintained over a median
      follow-up period of 38 months (18-62 months). CONCLUSION: Sacral neuromodulation
      can provide long-term symptom relief in selected patients with severe
      constipation. Sacral neuromodulation should be incorporated into the treatment
      algorithm for chronic constipation.

PMID- 21717094
TI  - Assessment of smoking behaviour in the dental setting. A study comparing self
      reported questionnaire data and exhaled carbon monoxide levels.
AB  - The present study validated the accuracy of data from a self-reported
      questionnaire on smoking behaviour with the use of exhaled carbon monoxide (CO)
      level measurements in two groups of patients. Group 1 included patients referred
      to an oral medicine unit, whereas group 2 was recruited from the daily outpatient
      service. All patients filled in a standardized questionnaire regarding their
      current and former smoking habits. Additionally, exhaled CO levels were measured
      using a monitor. A total of 121 patients were included in group 1, and 116
      patients were included in group 2. The mean value of exhaled CO was 7.6 ppm in
      the first group and 9.2 ppm in the second group. The mean CO values did not
      statistically significantly differ between the two groups. The two exhaled CO
      level measurements taken for each patient exhibited very good correlation
      (Spearman's coefficient of 0.9857). Smokers had a mean difference of exhaled CO
      values of 13.95 ppm (p < 0.001) compared to non-smokers adjusted for the first or
      second group. The consumption of one additional pack year resulted in an increase
      in CO values of 0.16 ppm (p = 0.003). The consumption of one additional cigarette
      per day elevated the CO measurements by 0.88 ppm (p < 0.001). Based on these
      results, the correlations between the self-reported smoking habits and exhaled CO
      values are robust and highly reproducible. CO monitors may offer a non-invasive
      method to objectively assess current smoking behaviour and to monitor tobacco use
      cessation attempts in the dental setting.

PMID- 21717095
TI  - Effect of single-dose amoxicillin on rat incisor odontogenesis: a morphological
      study.
AB  - The effect of exposure to amoxicillin on tooth development remains to be
      elucidated. The purpose of this study was to investigate the effect of
      amoxicillin on rat incisor odontogenesis. Male Wistar rats weighing approximately
      100 g were given a single intraperitoneal injection of 3.0 g/kg body weight
      amoxicillin. One week after injection, the rats were fixed, and the lower
      incisors were demineralized and prepared into paraffin sections for light
      microscopy (LM) and immunohistochemistry. Undemineralized samples were embedded
      in resin and ground for processing for contact microradiography (CMR) and
      scanning electron microscopy (SEM). Serum calcium, phosphate, and magnesium
      concentrations were measured. At 1 week after amoxicillin administration, LM,
      CMR, and SEM revealed a clear increase in the area of interglobular dentin,
      representing disruption of mineralization by odontoblasts. Immunohistochemistry
      demonstrated moderate levels of the small integrin-binding ligand N-linked
      glycoprotein family dentin matrix protein 1 in large areas of interglobular
      dentin. On the other hand, no morphological alteration or hypomineralization was
      observed in the enamel. Serum calcium values showed no significant differences
      between the control and experimental rats during the experimental period although
      both serum phosphate and magnesium levels increased at day 1 after amoxicillin
      injection. The results suggest that a single dose of amoxicillin specifically
      affects normal tooth dentin mineralization, but not enamel mineralization in rat
      incisor odontogenesis. The present results further our understanding of the
      clinical association between dentin abnormality and amoxicillin exposure during
      tooth development.

PMID- 21717096
TI  - Tuning of the ocular vestibular evoked myogenic potential (oVEMP) to AC sound
      shows two separate peaks.
AB  - The ocular vestibular evoked myogenic potential (oVEMP) is a relatively new
      method used to assess otolith-ocular pathways in humans. When elicited using air
      conducted (AC) sound stimulation, the oVEMP is thought to reflect mostly saccular
      activation. However, it has been recently suggested that utricular afferents may
      also contribute to the AC evoked oVEMP. While previous frequency tuning studies
      of the AC evoked oVEMP report predominately high frequency sensitivity (>400 Hz),
      few have included the lower frequencies (<200 Hz) at which it has been proposed
      the utricle is most sensitive. In this study, ten normal subjects were stimulated
      with AC sound delivered unilaterally using headphones over frequencies from 50 to
      1,200 Hz at a near constant A-weighted intensity of 120 dB peak sound pressure
      level. For AC stimulation, the oVEMP demonstrated maximum amplitudes around 600
      Hz, with a second, smaller peak occurring around 100 Hz. The AC evoked oVEMP
      tuning has two peaks, a dominant one consistent with excitation of the saccule
      and a smaller one consistent with excitation of the utricle.

PMID- 21717097
TI  - Juggling reveals a decisional component to tactile suppression.
AB  - Goal-directed movements are characterized by sensory suppression, that is, by
      decreased sensitivity to tactile stimuli. In the present study, we investigated
      tactile suppression during movement using a complex motor task: basic 3-ball
      juggling. It was hypothesized that a decrease in tactile sensitivity would be
      observed, together with a shift in participants' response bias while juggling. In
      a first experiment, participants had to detect a short gap in an otherwise
      continuous vibratory stimulus, which was delivered to their wrist under
      conditions of rest or else while juggling. In a second experiment, participants
      detected a short time gap in a continuous auditory signal, under the same
      conditions. In a final control experiment performed at rest, participants
      detected a short time gap in an auditory or tactile signal. In an additional
      condition, the detection of a gap in tactile stimulation was required under
      conditions of intramodal tactile interference. Participants were significantly
      less sensitive to detect a gap in tactile stimulation whilst juggling. Most
      importantly, these results were paired with a significant shift toward
      participants adopting a more conservative criterion when responding to the
      presence of the gap (i.e. they were more likely to say that a gap was not
      present). Taken together, these results demonstrate movement-related tactile
      sensory suppression and point to a decisional component in tactile suppression,
      thus suggesting that tactile suppression could already be triggered in the brain
      ahead of the motor command.

PMID- 21717098
TI  - EMG feedback tasks reduce reflexive stiffness during force and position
      perturbations.
AB  - Force and position perturbations are widely applied to identify muscular and
      reflexive contributions to posture maintenance of the arm. Both task instruction
      (force vs. position) and the inherently linked perturbation type (i.e., force
      perturbations-position task and position perturbations-force tasks) affect these
      contributions and their mutual balance. The goal of this study is to explore the
      modulation of muscular and reflexive contributions in shoulder muscles using EMG
      biofeedback. The EMG biofeedback provides a harmonized task instruction to
      facilitate the investigation of perturbation type effects irrespective of task
      instruction. External continuous force and position perturbations with a
      bandwidth of 0.5-20 Hz were applied at the hand while subjects maintained
      prescribed constant levels of muscular co-activation using visual feedback of an
      EMG biofeedback signal. Joint admittance and reflexive impedance were identified
      in the frequency domain, and parametric identification separated intrinsic
      muscular and reflexive feedback properties. In tests with EMG biofeedback,
      perturbation type (position and force) had no effect on joint admittance and
      reflexive impedance, indicating task as the dominant factor. A reduction in
      muscular and reflexive stiffness was observed when performing the EMG biofeedback
      task relative to the position task. Reflexive position feedback was effectively
      suppressed during the equivalent EMG biofeedback task, while velocity and
      acceleration feedback were both decreased by approximately 37%. This indicates
      that force perturbations with position tasks are a more effective paradigm to
      investigate complete dynamic motor control of the arm, while EMG tasks tend to
      reduce the reflexive contribution.

PMID- 21717099
TI  - Neural markers of automatic and controlled attention during immediate and delayed
      action.
AB  - It has been shown that visually guided and memory-guided actions are under the
      control of dissociable neural systems. This experiment measured event-related
      potentials (ERPs) in a cross-modal dual-task paradigm to investigate the
      attentional requirements of these two types of actions. In a primary joystick
      controlled continuous reciprocal aiming task, participants moved a cursor back
      and forth between two targets of variable size in visually guided (VIS) and
      memory-guided (MEM) conditions. In a secondary dichotic listening task, ERPs were
      collected while infrequent high and frequent low pitch tones were delivered to
      both ears. Participants responded to the infrequent tones delivered to only one
      attended ear. Aiming and listening were performed separately and together as a
      dual task. We were interested in two ERP components: the P300 component, which
      reflects voluntary attention, and the mismatch negativity (MMN), which reflects
      automatic attention. The results showed that the P300 component elicited by the
      auditory task was decreased in amplitude by the dual-task conditions compared
      with the auditory task alone. Moreover, P300 latency was increased by the MEM
      aiming condition, but not the VIS aiming condition. On the other hand, the MMN
      component elicited by the auditory task was only attenuated by the VIS aiming
      condition, not by the MEM aiming condition. Together, these results suggest that
      memory-guided aiming requires more voluntary attention and less automatic
      attention than visually guided aiming.

PMID- 21717101
TI  - Excitability and recruitment patterns of spinal motoneurons in human sleep as
      assessed by F-wave recordings.
AB  - This study examines the excitability and recruitment of spinal motoneurons in
      human sleep. The main objective was to assess whether supraspinal inhibition
      affects the different subpopulations of the compound spinal motoneuron pool in
      the same way or rather in a selective fashion in the various sleep stages. To
      this end, we studied F-conduction velocities (FCV) and F-tacheodispersion
      alongside F-amplitudes and F-persistence in 22 healthy subjects in sleep stages
      N2, N3 (slow-wave sleep), REM and in wakefulness. Stimuli were delivered on the
      ulnar nerve, and F-waves were recorded from the first dorsal interosseus muscle.
      Repeated sets of stimuli were stored to obtain at least 15 F-waves for each state
      of vigilance. F-tacheodispersion was calculated based on FCVs using the modified
      Kimura formula. Confirming the only previous study, excitability of spinal
      motoneurons was generally decreased in all sleep stages compared with wakefulness
      as indicated by significantly reduced F-persistence and F-amplitudes. More
      importantly, F-tacheodispersion showed a narrowed range of FCV in all sleep
      stages, most prominently in REM. In non-REM, this narrowed range was associated
      with a shift towards significantly decreased maximal FCV and mean FCV as well as
      with a trend towards lower minimal FCV. In REM, the lowering of mean FCV was even
      more pronounced, but contrary to non-REM sleep without a shift of minimal and
      maximal FCV. Variations in F-tacheodispersion between sleep stages suggest that
      different supraspinal inhibitory neuronal circuits acting on the spinal
      motoneuron pool may contribute to muscle hypotonia in human non-REM sleep and to
      atonia in REM sleep.

PMID- 21717102
TI  - The novel compound OSI-461 induces apoptosis and growth arrest in human acute
      myeloid leukemia cells.
AB  - Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy.
      Treatment of patients suffering from high-risk AML as defined by clinical
      parameters, cytogenetics, and/or molecular analyses is often unsuccessful. OSI
      461 is a pro-apoptotic compound that has been proposed as a novel therapeutic
      option for patients suffering from solid tumors like prostate or colorectal
      carcinoma. But little is known about its anti-proliferative potential in AML.
      Hence, we treated bone marrow derived CD34(+) selected blast cells from 20 AML
      patients and the five AML cell lines KG-1a, THP-1, HL-60, U-937, and MV4-11 with
      the physiologically achievable concentration of 1 MUM OSI-461 or equal amounts of
      DMSO as a control. Following incubation with OSI-461, we found a consistent
      induction of apoptosis and an accumulation of cells in the G2/M phase of the cell
      cycle. In addition, we demonstrate that the OSI-461 mediated anti-proliferative
      effects observed in AML are associated with the induction of the pro-apoptotic
      cytokine mda-7/IL-24 and activation of the growth arrest and DNA-damage inducible
      genes (GADD) 45alpha and 45gamma. Furthermore, OSI-461 treated leukemia cells did
      not regain their proliferative potential for up to 8 days after cessation of
      treatment following the initial 48 h treatment period with 1 MUM OSI-461. This
      indicates sufficient targeting of the leukemia-initiating cells in our in vitro
      experiments through OSI-461. The AML samples tested in this study included
      samples from patients who were resistant to conventional chemotherapy and/or had
      FLT3-ITD mutations demonstrating the high potential of OSI-461 in human AML.

PMID- 21717103
TI  - Critical remarks on the proposed "extended retrosigmoid approach".

PMID- 21717104
TI  - Finite volume and asymptotic methods for stochastic neuron models with correlated
      inputs.
AB  - We consider a pair of stochastic integrate and fire neurons receiving correlated
      stochastic inputs. The evolution of this system can be described by the
      corresponding Fokker-Planck equation with non-trivial boundary conditions
      resulting from the refractory period and firing threshold. We propose a finite
      volume method that is orders of magnitude faster than the Monte Carlo methods
      traditionally used to model such systems. The resulting numerical approximations
      are proved to be accurate, nonnegative and integrate to 1. We also approximate
      the transient evolution of the system using an Ornstein-Uhlenbeck process, and
      use the result to examine the properties of the joint output of cell pairs. The
      results suggests that the joint output of a cell pair is most sensitive to
      changes in input variance, and less sensitive to changes in input mean and
      correlation.

PMID- 21717105
TI  - CD8+ cytotoxic T cell and FOXP3+ regulatory T cell infiltration in relation to
      breast cancer survival and molecular subtypes.
AB  - The prognostic significance of tumor-associated FOXP3(+) regulatory T cells
      (Tregs) and CD8(+) cytotoxic T lymphocytes (CTLs) in invasive breast carcinomas
      is studied. Tregs and CTLs were assessed by immunohistochemistry in 1270 cases of
      invasive breast carcinoma for their associations with patient survival,
      histopathologic features, and molecular subtypes. Infiltrates of Tregs and CTLs
      were observed within tumor bed and in the tissue surrounding tumor. Within tumor
      bed, increased infiltration of Tregs and CTLs was significantly more common in
      those with unfavorable histologic features, including high histologic grade and
      negative ER and PR status. In addition, high density Treg infiltration was also
      associated with tumor HER2 overexpression, decreased overall survival (OS) and
      progression-free survival (PFS). In tissue surrounding tumor, in contrast, high
      CTL/Treg ratio was found to be significantly associated with improved OS and PFS.
      These prognostic associations were confirmed by multivariate analysis.
      Furthermore, the density of Treg infiltrates within tumors was inversely
      correlated with the prognosis of the molecular subtypes of tumors. The ratio of
      CTL/Treg infiltrates in the surrounding tissue was also significantly higher in
      luminal than non-luminal subtypes of carcinoma. The prognostic significances of
      Tregs and CTLs in breast carcinoma depend on their relative density and location.
      The density of intratumoral Treg infiltrates and the peritumoral CTL/Treg ratio
      are independent prognostic factors and correlated with the prognosis of the
      molecular subtypes of breast carcinoma, which may serve as potential target for
      stratifying immunotherapy to battle against the aggressive subtypes of breast
      carcinoma.

PMID- 21717106
TI  - Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with
      early recurrence and non-Caucasian ethnicity.
AB  - African American and Hispanic women develop more triple negative breast cancer at
      younger ages than Caucasian women. The frequently observed association between
      race and socioeconomic status (SES) has confounded our understanding of the
      outcomes disparities seen in these groups. Given the association between
      inflammatory cells and high-grade, triple negative tumors, we sought to
      investigate whether differences in the presence of these cells varies by race. We
      evaluated breast tumor specimens for the presence PCNA+ tumor-associated
      macrophages (TAMs) in consecutive cases from a county hospital serving primarily
      un- or under-insured patients. All patients in this cohort had elevated PCNA +
      TAM levels. Higher PCNA + TAM counts were associated with hormone receptor (HR)
      negative tumors and non-Caucasian ethnicity. Hispanic women specifically had
      significantly higher PCNA + TAM counts than Caucasian patients and shorter
      disease-free survival. These findings implicate immune function in the
      development of aggressive breast cancer and suggest a possible link between SES
      and the inflammatory response.

PMID- 21717107
TI  - PIAS1 negatively regulates ubiquitination of Msx1 homeoprotein independent of its
      SUMO ligase activity.
AB  - Posttranslational modifications play key roles in many cellular processes
      including proliferation and differentiation by modulating the activities of
      target proteins. PIAS1, a member of PIAS family of protein, mediates the
      modification of protein by SUMO and thereby regulates the function of its
      interacting protein partners. Here we report that PIAS1 negatively regulates
      ubiquitination of Msx1 homeoprotein, a regulator of myogenic differentiation, in
      a SUMO-independent manner. We demonstrate that ubiquitination and SUMOylation of
      Msx1 are not mutually exclusive but require the same C-terminal PIAS1 interaction
      domain. In addition, deletion of C-terminal domain increases the steady-state
      protein level of Msx1, while mutations of SUMO acceptor sites have no significant
      effect on the stability of Msx1 proteins. Moreover, we find that forced
      expression of PIAS1 inhibits ubiquitination and thereby increases the stability
      of Msx1 protein regardless of its activity as a SUMO ligase. Furthermore,
      repressor activity of Msx1 in transcription is strengthened in the presence of
      PIAS1. Taken together, our studies uncover a new function of PIAS1, which is to
      control the stability of its interacting protein partner in a SUMO independent
      manner.

PMID- 21717108
TI  - Expression of hepatic and ovarian cytochrome P450 during estrous cycle in rats.
AB  - It is known that gender differences in drug metabolism are largely attributed to
      changes in sex and growth hormones. Serum concentrations of estradiol,
      progesterone, prolactin, follicle-stimulating hormone, and luteinizing hormone
      change markedly during the human menstrual cycle and the rat estrous cycle.
      However, little information is available regarding the effects of the human
      menstrual cycle or the rat estrous cycle on expression and activity of cytochrome
      P450 (CYP) isoforms. The present study was carried out to determine the
      expression and activity of CYP-dependent drug-metabolizing enzymes in the liver
      and ovary during the estrous cycle. The expression and activity of microsomal CYP
      isoforms (CYP1A1, CYP1A2, CYP1B1, CYP2B1, CYP2C11, CYP2C12, CYP2E1, CYP3A1,
      CYP3A2, and CYP4A), cytochrome b(5) and NADPH-dependent CYP reductase in the
      liver and ovary were measured in female rats in diestrus and proestrus. Our
      results indicated that hepatic and ovarian expression and activity of CYP
      isoforms, cytochrome b(5), and NADPH-dependent CYP reductase were not different
      between diestrus and proestrus, although serum estradiol concentration and uterus
      weight were markedly increased in the proestrus phase. These results suggest that
      the cytochrome P450-dependent system is not sensitive to changes in the estrous
      cycle, and further studies are warranted to determine the effects of the estrous
      cycle on in vivo metabolism of xenobiotics.

PMID- 21717109
TI  - The safety profile of imatinib in CML and GIST: long-term considerations.
AB  - Imatinib mesylate is considered the standard first-line systemic treatment for
      patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour
      (GIST) by targeting BCR-ABL and c-KIT tyrosine kinases, respectively. Indeed,
      imatinib has substantially changed the clinical management and improved the
      prognosis of both diseases. Treatment with imatinib is generally well tolerated,
      and the risk for severe adverse effects is low, generally occurring during the
      early phase of treatment and correlating with imatinib dose, phase of disease and
      patient's characteristics. This article summarises recent data on safety profile
      of imatinib for the treatment of CML and GIST, including long-term side effects.
      Prolonged treatment with imatinib in both diseases demonstrates excellent
      tolerability. There are few significant concerns and those that have emerged,
      like cardiotoxicity, have far turned out to be exaggerated.

PMID- 21717110
TI  - Muller's Nobel lecture on dose-response for ionizing radiation: ideology or
      science?
AB  - In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that
      the dose-response for radiation-induced germ cell mutations was linear and that
      there was "no escape from the conclusion that there is no threshold". However,
      assessment of correspondence between Muller and Curt Stern 1 month prior to his
      Nobel Prize Lecture reveals that Muller knew the results and implications of a
      recently completed study at the University of Rochester under the direction of
      Stern, which directly contradicted his Nobel Prize Lecture. This finding is of
      historical importance since Muller's Nobel Lecture gained considerable
      international attention and is a turning point in the acceptance of the linearity
      model in risk assessment for germ cell mutations and carcinogens.

PMID- 21717111
TI  - Effects of an anionic surfactant (FFD-6) on the energy and information flow
      between a primary producer (Scenedesmus obliquus) and a consumer (Daphnia magna).
AB  - The effects of a commercially available anionic surfactant solution (FFD-6) on
      growth and morphology of a common green alga (Scenedesmus obliquus) and on
      survival and clearance rates of the water flea Daphnia magna were studied. The
      surfactant-solution elicited a morphological response (formation of colonies) in
      Scenedesmus at concentrations of 10-100 MUl l(-1) that were far below the No
      Observed Effect Concentration (NOEC) value of 1,000 MUl l(-1) for growth
      inhibition. The NOEC-value of FFD-6 for colony-induction was 3 MUl l(-1). Daphnia
      survival was strongly affected by FFD-6, yielding LC(50-24h) and LC(50-48 h) of
      148 and 26 MUl l(-1), respectively. In addition, clearance rates of Daphnia
      feeding on unicellular Scenedesmus were inhibited by FFD-6, yielding a 50%
      inhibition (EC(50-1.5h)) at 5.2 MUl l(-1) with a NOEC of 0.5 MUl l(-1). When
      Daphnia were offered FFD-6-induced food in which eight-celled colonies (43 * 29
      MUm) were most abundant, clearance rates (~0.14 ml ind.(-1) h(-1)) were only 25%
      the rates of animals that were offered non-induced unicellular (15 * 5 MUm)
      Scenedesmus (~0.56 ml ind.(-1) h(-1)). As FFD-6 concentrations in the treated
      food used in the experiments were far below the NOEC for clearance rate
      inhibition, it is concluded that the feeding rate depression was caused by the
      altered morphology of the Scenedesmus moving them out of the feeding window of
      the daphnids. The surfactant evoked a response in Scenedesmus that is similar to
      the natural chemically induced defensive reaction against grazers and could
      disrupt the natural information conveyance between these plankton organisms.

PMID- 21717112
TI  - MeCAT--new iodoacetamide reagents for metal labeling of proteins and peptides.
AB  - Besides protein identification via mass spectrometric methods, protein and
      peptide quantification has become more and more important in order to tackle
      biological questions. Methods like differential gel electrophoresis or enzyme
      linked immunosorbent assays have been used to assess protein concentrations,
      while stable isotope labeling methods are also well established in quantitative
      proteomics. Recently, we developed metal-coded affinity tagging (MeCAT) as an
      alternative for accurate and sensitive quantification of peptides and proteins.
      In addition to absolute quantification via inductively coupled plasma mass
      spectrometry, MeCAT also enables sequence analysis via electrospray ionization
      tandem mass spectrometry. In the current study, we developed a new labeling
      approach utilizing an iodoacetamide MeCAT reagent (MeCAT-IA). The MeCAT-IA
      approach shows distinct advantages over the previously used MeCAT with
      maleinimide reactivity such as higher labeling efficiency and the lack of
      diastereomer formation during labeling. Here, we present a careful
      characterization of this new method focusing on the labeling process, which
      yields complete tagging with an excess of reagent of 1.6 to 1, less complex
      chromatographic behavior, and fragmentation characteristics of the tagged
      peptides using the iodoacetamide MeCAT reagent.

PMID- 21717113
TI  - Immunochemical analysis of 3-phenoxybenzoic acid, a biomarker of forestry worker
      exposure to pyrethroid insecticides.
AB  - Pyrethroid insecticides widely used in forestry, agricultural, industrial, and
      residential applications have potential for human exposure. Short sample
      preparation time and sensitive, economical high-throughput assays are needed for
      biomonitoring studies that analyze a large number of samples. An enzyme-linked
      immunosorbent assay (ELISA) was used for determining 3-phenoxybenzoic acid (3
      PBA), a general urinary biomarker of exposure to some pyrethroid insecticides. A
      mixed-mode solid-phase extraction reduced interferences from acid hydrolyzed
      urine and gave 110 +/- 6% recoveries from spiked samples. The method limit of
      quantification was 2 MUg/L. Urine samples were collected from forestry workers
      that harvest pine cone seeds where pyrethroid insecticides were applied at ten
      different orchards. At least four samples for each worker were collected in a 1
      week period. The 3-PBA in workers classified as high, low, or no exposure based
      on job analysis over all sampling days was 6.40 +/- 9.60 (n = 200), 5.27 +/- 5.39
      (n = 52), and 3.56 +/- 2.64 ng/mL (n = 34), respectively. Pair-wise comparison of
      the differences in least squares means of 3-PBA concentrations among groups only
      showed a significant difference between high and no exposure. Although this
      difference was not significant when 3-PBA excretion was normalized by creatinine
      excretion, the general trend was still apparent. No significant differences were
      observed among days or orchards. This ELISA method using a 96-well plate was
      performed as a high-throughput tool for analyzing around 300 urine samples
      measured in triplicate to provide data for workers exposure assessment.

PMID- 21717114
TI  - Ezrin is associated with gastric cancer progression and prognosis.
AB  - To investigat the clinical significance of Ezrin in the development and
      progression of gastric cancer. Immunohistochemistry was employed to analyze Ezrin
      expression in 436 clinicopathologically characterized gastric cancer cases. Ezrin
      protein levels were up-regulated in gastric cancer lesions compared with adjacent
      noncancerous tissues. Positive expression of Ezrin correlated with age, size of
      tumor, location of tumor, depth of invasion, vessel invasion, lymph node and
      distant metastasis and TNM stage. In stages I, II and III, the 5 year survival
      rate of patients with a high expression of Ezrin was significantly lower than
      those in patients with low expression. In stage IV, Ezrin expression did not
      correlate with the 5 year survival rate. Further multivariate analysis suggested
      that the depth of invasion, lymph node and distant metastasis, TNM stage, and up
      regulation of Ezrin were independent prognostic indicators for the disease.
      Expression of Ezrin in gastric cancer is significantly associated with lymph node
      and distant metastasis, and poor prognosis. Ezrin protein could be useful markers
      to predict tumor progression and prognosis.

PMID- 21717115
TI  - No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian
      randomisation approach.
AB  - AIMS/HYPOTHESIS: Epidemiological and experimental evidence suggests that uric
      acid has a role in the aetiology of type 2 diabetes. Using a Mendelian
      randomisation approach, we investigated whether there is evidence for a causal
      role of serum uric acid for development of type 2 diabetes. METHODS: We examined
      the associations of serum-uric-acid-raising alleles of eight common variants
      recently identified in genome-wide association studies and summarised this in a
      genetic score with type 2 diabetes in case-control studies including 7,504
      diabetes patients and 8,560 non-diabetic controls. We compared the observed
      effect size to that expected based on: (1) the association between the genetic
      score and uric acid levels in non-diabetic controls; and (2) the meta-analysed
      uric acid level to diabetes association. RESULTS: The genetic score showed a
      linear association with uric acid levels, with a difference of 12.2 MUmol/l (95%
      CI 9.3, 15.1) by score tertile. No significant associations were observed between
      the genetic score and potential confounders. No association was observed between
      the genetic score and type 2 diabetes with an OR of 0.99 (95% CI 0.94, 1.04) per
      score tertile, significantly different (p = 0.046) from that expected (1.04 [95%
      CI 1.03, 1.05]) based on the observed uric acid difference by score tertile and
      the uric acid to diabetes association of 1.21 (95% CI 1.14, 1.29) per 60 MUmol/l.
      CONCLUSIONS/INTERPRETATION: Our results do not support a causal role of serum
      uric acid for the development of type 2 diabetes and limit the expectation that
      uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes.

PMID- 21717116
TI  - Design and cohort description of the InterAct Project: an examination of the
      interaction of genetic and lifestyle factors on the incidence of type 2 diabetes
      in the EPIC Study.
AB  - AIMS/HYPOTHESIS: Studying gene-lifestyle interaction may help to identify
      lifestyle factors that modify genetic susceptibility and uncover genetic loci
      exerting important subgroup effects. Adequately powered studies with prospective,
      unbiased, standardised assessment of key behavioural factors for gene-lifestyle
      studies are lacking. This case-cohort study aims to investigate how genetic and
      potentially modifiable lifestyle and behavioural factors, particularly diet and
      physical activity, interact in their influence on the risk of developing type 2
      diabetes. METHODS: Incident cases of type 2 diabetes occurring in European
      Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991
      and 2007 from eight of the ten EPIC countries were ascertained and verified.
      Prentice-weighted Cox regression and random-effects meta-analyses were used to
      investigate differences in diabetes incidence by age and sex. RESULTS: A total of
      12,403 verified incident cases of type 2 diabetes occurred during 3.99 million
      person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We
      defined a centre-stratified subcohort of 16,154 individuals for comparative
      analyses. Individuals with incident diabetes who were randomly selected into the
      subcohort (n = 778) were included as cases in the analyses. All prevalent
      diabetes cases were excluded from the study. InterAct cases were followed-up for
      an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis
      were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4
      kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively.
      Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56
      (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess
      in the risk of incident diabetes was consistently observed across all countries,
      with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age.
      CONCLUSIONS/INTERPRETATION: InterAct is a large, well-powered, prospective study
      that will inform our understanding of the interplay between genes and lifestyle
      factors on the risk of type 2 diabetes development.

PMID- 21717117
TI  - Inhibition of T-cell responses by intratumoral hepatic stellate cells contribute
      to migration and invasion of hepatocellular carcinoma.
AB  - The stroma of hepatocellular carcinoma (HCC) is markedly infiltrated with
      activated hepatic stellate cells (HSCs), and associated invasion and metastasis
      of HCC. However, little is known of the role of HSCs in immune responses in HCC.
      The Buffalo rat HCC model was established. Quiescent HSCs (qHSCs) and
      intratumoral HSCs (tHSCs) were isolated. Surface molecules of tHSC were detected
      by flow cytometry, and gene expression was analyzed by fluorescence quantitative
      RT-PCR. T cell proliferation was monitored by [(3)H]-thymidine ((3)H-TdR)
      incorporation into DNA, and cytotoxic activity was assessed by measuring the
      release of (51)Cr. The level of cytokine expression by T cells was measured by
      enzyme-linked immunosorbent assay. T cell apoptosis was detected by double
      stained terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      (TUNEL) and anti-CD3 antibodies. The migration and invasion of HCC was observed
      by transwell experiments. tHSCs express low levels of major histocompatibility
      complex (MHC) class I, MHC class II, and costimulatory molecules, and produce
      varying levels of cytokines. Addition of the tHSCs suppressed thymidine uptake by
      T cells that were stimulated by alloantigens or by anti-CD3-mediated T-cell
      receptor ligation. The tHSC-induced T-cell hyporesponsiveness was associated with
      enhanced T-cell apoptosis, and contributed to the migration and invasion of
      hepatoma cell. tHSCs was associated with markedly enhanced expression of B7-H1.
      Blockade of B7-H1/PD-1 ligation significantly reduced HSC immunomodulatory
      activity, and hepatoma cell migration and invasion. tHSCs can induce T cell
      apoptosis, suggesting an important role for B7-H1. The interactions between tHSCs
      and T cells may contribute to hepatic immune tolerance and invasion and migration
      of HCC.

PMID- 21717118
TI  - Oral administration of copper to rats leads to increased lymphocyte cellular DNA
      degradation by dietary polyphenols: implications for a cancer preventive
      mechanism.
AB  - To account for the observed anticancer properties of plant polyphenols, we have
      earlier proposed a mechanism which involves the mobilization of endogenous copper
      ions by polyphenols leading to the generation of reactive oxygen species (ROS)
      that serve as proximal DNA cleaving agents and lead to cell death. Over the last
      decade we have proceeded to validate our hypothesis with considerable success. As
      a further confirmation of our hypothesis, in this paper we first show that oral
      administration of copper to rats leads to elevated copper levels in lymphocytes.
      When such lymphocytes with a copper overload were isolated and treated with
      polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage
      was observed. Further, preincubation of lymphocytes having elevated copper levels
      with the membrane permeable copper chelator neocuproine, resulted in inhibition
      of polyphenol induced DNA degradation. However, membrane impermeable chelator of
      copper bathocuproine, as well as iron and zinc chelators were ineffective in
      causing such inhibition in DNA breakage, confirming the involvement of endogenous
      copper in polyphenol induced cellular DNA degradation. It is well established
      that serum and tissue concentrations of copper are greatly increased in various
      malignancies. In view of this fact, the present results further confirm our
      earlier findings and strengthen our hypothesis that an important anticancer
      mechanism of plant polyphenols could be the mobilization of intracellular copper
      leading to ROS-mediated cellular DNA breakage. In this context, it may be noted
      that cancer cells are under considerable oxidative stress and increasing such
      stress to cytotoxic levels could be a successful anticancer approach.

PMID- 21717119
TI  - Exercise intensity and oxygen uptake kinetics in African-American and Caucasian
      women.
AB  - The effect of exercise intensity on the on- and off-transient kinetics of oxygen
      uptake (VO(2)) was investigated in African American (AA) and Caucasian (C) women.
      African American (n = 7) and Caucasian (n = 6) women of similar age, body mass
      index and weight, performed an incremental test and bouts of square-wave exercise
      at moderate, heavy and very heavy intensities on a cycle ergometer. Gas exchange
      threshold (LT(GE)) was lower in AA (13.6 +/- 2.3 mL kg(-1) min(-1)) than C (18.6
      +/- 5.6 mL kg(-1) min(-1)). The dynamic exercise and recovery VO(2) responses
      were characterized by mathematical models. There were no significant differences
      in (1) peak oxygen uptake (VO(2peak)) between AA (28.5 +/- 5 mL kg(-1) min(-1))
      and C (31.1 +/- 6.6 mL kg(-1) min(-1)) and (2) VO(2) kinetics at any exercise
      intensity. At moderate exercise, the on- and off- VO(2) kinetics was described by
      a monoexponential function with similar time constants tau (1,on) (39.4 +/- 12.5;
      38.8 +/- 15 s) and tau (1,off) (52.7 +/- 10.1; 40.7 +/- 4.4 s) for AA and C,
      respectively. At heavy and very heavy exercise, the VO(2) kinetics was described
      by a double-exponential function. The parameter values for heavy and very heavy
      exercise in the AA group were, respectively: tau (1,on) (47.0 +/- 10.8; 44.3 +/-
      10 s), tau (2,on) (289 +/- 63; 219 +/- 90 s), tau (1,off) (45.9 +/- 6.2; 50.7 +/-
      10 s), tau (2,off) (259 +/- 120; 243 +/- 93 s) while in the C group were,
      respectively: tau (1,on) (41 +/- 12; 43.2 +/- 15 s); tau (2, on) (277 +/- 81; 215
      +/- 36 s), tau (1,off) (40.2 +/- 3.4; 42.3 +/- 7.2 s), tau (2,off) (215 +/- 133;
      228 +/- 64 s). The on- and off-transients were symmetrical with respect to model
      order and dependent on exercise intensity regardless of race. Despite similar
      VO(2) kinetics, LT(GE) and gain of the VO(2) on-kinetics at moderate intensity
      were lower in AA than C. However, generalization to the African American and
      Caucasian populations is constrained by the small subject numbers.

PMID- 21717120
TI  - Peak and submaximal steady-state metabolic and cardiorespiratory responses during
      arm-powered and arm-trunk-powered handbike ergometry in able-bodied participants.
AB  - The purpose of this study was to compare the peak and submaximal metabolic and
      cardiorespiratory responses during steady-state arm-powered (AP) and arm-trunk
      powered (ATP) handbike ergometry. Twelve male able-bodied participants with no
      prior experience in handcycling completed a maximal progressive incremental test
      and a series of 6-minute submaximal tests at 130 W with various cadences in a
      custom-designed handbike ergometer that allowed a realistic simulation of AP and
      ATP handcycling. Peak power output, peak oxygen uptake, and peak ventilation were
      significantly lower, whereas peak blood lactate concentration was significantly
      higher during AP handcycling. Mean gross mechanical efficiency was significantly
      higher during AP handcycling (range 16.7 to 20.5%) compared with ATP handcycling
      (range 15.8 to 17.6%). These results suggest that AP handcycling is advantageous
      during submaximal steady-state handcycling, whereas ATP handcycling allows for a
      higher peak power output generation. However, it remains unclear which handbike
      configuration would be favorable during competition.

PMID- 21717121
TI  - Passing the anaerobic threshold is associated with substantial changes in the
      gene expression profile in white blood cells.
AB  - High and moderate intensity endurance exercise alters gene expression in human
      white blood cells (WBCs), but the understanding of how this effect occurs is
      limited. To increase our knowledge of the nature of this process, we investigated
      the effects of passing the anaerobic threshold (AnT) on the gene expression
      profile in WBCs of athletes. Nineteen highly trained skiers participated in a
      treadmill test with an incremental step protocol until exhaustion (ramp test to
      exhaustion, RTE). The average total time to exhaustion was 14:40 min and time
      after AnT was 4:50 min. Two weeks later, seven of these skiers participated in a
      moderate treadmill test (MT) at 80% peak O(2) uptake for 30 min, which was
      slightly below their AnTs. Blood samples were obtained before and immediately
      after both tests. RTE was associated with substantially greater leukocytosis and
      acidosis than MT. Gene expression in WBCs was measured using whole genome
      microarray expression analysis before and immediately after each test. A total of
      310 upregulated genes were found after RTE, and 69 genes after MT of which 64
      were identical to RTE. Both tests influenced a variety of known gene pathways
      related to inflammation, stress response, signal transduction and apoptosis. A
      large group of differentially expressed previously unknown small nucleolar RNA
      and small Cajal body RNA was found. In conclusion, a 15-min test to exhaustion
      was associated with substantially greater changes of gene expression than a 30
      min test just below the AnT.

PMID- 21717122
TI  - Transcutaneous neuromuscular electrical stimulation: influence of electrode
      positioning and stimulus amplitude settings on muscle response.
AB  - The aim of the study was to investigate the influence of two different
      transcutaneous neuromuscular electrical stimulation procedures on evoked muscle
      torque and local tissue oxygenation. In the first one (MP mode), the cathode was
      facing the muscle main motor point and stimulus amplitude was set to the level
      eliciting the maximal myoelectrical activation according to the amplitude of the
      evoked electromyogram (EMG); in the second one (RC mode), the electrodes were
      positioned following common reference charts for electrode placement while
      stimulus amplitude was set according to subject tolerance. Tibialis Anterior (TA)
      and Vastus Lateralis (VL) muscles of 10 subjects (28.4 +/- 8.2 years) were tested
      in specific dynamometers to measure the evoked isometric torque. The EMG and near
      infrared spectroscopy probes were placed on muscle belly to detect the electrical
      activity and local metabolic modifications of the stimulated muscle,
      respectively. The stimulation protocol consisted of a gradually increasing
      frequency ramp from 2 to 50 Hz in 7.5 s. Compared to RC mode, in MP mode the
      contractile parameters (peak twitch, tetanic torque, area under the torque build
      up) and the metabolic solicitation (oxygen consumption and hyperemia due to
      metabolites accumulation) resulted significantly higher for both TA and VL
      muscles. MP mode resulted also to be more comfortable for the subjects. Based on
      the assumption that proper mechanical and metabolic stimuli are necessary to
      induce muscle strengthening, our results witness the importance of an optimized,
      i.e., comfortable and effective, stimulation to promote the aforementioned muscle
      adaptive modifications.

PMID- 21717123
TI  - Oesophageal GIST: MDCT findings of two cases and review of the literature.
AB  - INTRODUCTION: The imaging findings of a gastrointestinal stromal tumour (GIST)
      have been investigated in various studies; however, the features and the pattern
      of growth of an oesophageal GIST have been described only in a few reports. We
      present two cases studied by multidetector computed tomography (MDCT) and we
      review the literature. METHODS: We describe the diagnostic course and the pattern
      of presentation at MDCT of two GISTs arising from the oesophageal wall that show
      two different behaviours and prognosis. We review the literature comparing the
      features of an oesophageal GIST to the more frequent gastric or intestinal GISTs,
      evaluating the role of MDCT in the diagnosis and in the follow-up. DISCUSSION AND
      CONCLUSION: Oesophageal GISTs are uncommon, with less than 5% of all reported
      cases originating from this site of the GI tract. In our experience, the CT
      features of the two oesophageal GISTs appeared comparable to the imaging findings
      of the gastrointestinal stromal tumours of the stomach and of the small bowel, as
      these neoplasms show signs and a pattern of growth that are fairly
      characteristic. As reported in literature and appear in our experience, MDCT has
      an important role in the diagnostic course and in staging the disease even if a
      definitive diagnosis can be only made with the support of an immunohistochemical
      examination. In addition, MDCT is extremely useful in monitoring patients
      surgically or pharmacologically treated in order to evaluate the response to the
      therapy and the possibility of a progression of the disease.

PMID- 21717124
TI  - Functional refolding and characterization of two Tom40 isoforms from human
      mitochondria.
AB  - Tom40 proteins represent an essential class of molecules which facilitate
      translocation of unfolded proteins from the cytosol into the mitochondrial
      intermembrane space. They are part of a high-molecular mass complex that forms
      the protein-conducting channel in outer mitochondrial membranes. This study
      concerns the recombinant expression, purification and folding of amino-terminally
      truncated variants of the two human Tom40 isoforms for structural biology
      experiments. Both CD and FTIR secondary structure analysis revealed a dominant
      beta-sheet structure and a short alpha-helical part for both proteins together
      with a high thermal stability. Two secondary structure elements can be denatured
      independently. Reconstitution of the recombinant protein into planar lipid
      bilayers demonstrated ion channel activity similar to Tom40 purified from
      Neurospora crassa mitochondrial membranes, but conductivity fingerprints differ
      from the structurally closely related VDAC proteins.

PMID- 21717125
TI  - Topological virtual screening: a way to find new compounds active in ulcerative
      colitis by inhibiting NF-kappaB.
AB  - Ulcerative colitis and Crohn's disease are chronic, immune-mediated inflammatory
      diseases of the gastrointestinal tract. Nuclear Factor Kappa B (NF-kappaB) is a
      transcription factor that plays a key role in regulating expression of multiple
      inflammatory and immune genes. In this study, a Topological Virtual Screening
      study has been carried out to achieve a model capable of finding new compounds
      active in ulcerative colitis by inhibiting NF-kappaB. Different topological
      indices were used as structural descriptors, and their relation to biological
      activity was determined using linear discriminant analysis. A topological model
      consisting of two discriminant functions was built up. The first function focused
      in the discrimination between NF-kappaB active and inactive compounds, and the
      second one in distinguishing between compounds active and inactive on ulcerative
      colitis. The model was then applied sequentially to a large database of compounds
      with unknown activity. Twenty-eight of such compounds were predicted to be active
      and selected for in vitro and in vivo testing.

PMID- 21717126
TI  - Evaluation of right ventricular dysfunction and prediction of clinical outcomes
      in acute pulmonary embolism by chest computed tomography: comparisons with
      echocardiography.
AB  - To evaluate the ability to identify right ventricular (RV) dysfunction, and to
      predict adverse outcomes of chest computed tomography (CT), we compared CT and
      echocardiography in acute pulmonary embolism patients. We analyzed 56 patients
      diagnosed by CT with acute pulmonary embolism, who underwent echocardiography
      within 48 h of CT scan from January 2004 to December 2008. From the CT scan, the
      ratio of RV diameter to left ventricular diameter (RVd/LVd), the presence of
      septal bowing and embolus location were determined. RVd/LVd (P < 0.001), septal
      bowing (P < 0.001) and proximal embolism (P = 0.016) were associated with
      echocardiographic RV hypokinesia. The odds ratio for adverse clinical outcomes
      was 19.2 for the combination of three CT parameters (RVd/LVd > 1, septal bowing,
      and proximal embolism), and 13.4 for RV hypokinesia (each P = 0.001). The
      positive predictive value (PPV) for adverse clinical outcomes for
      echocardiographic RV hypokinesia was 55.0%, and the negative predictive value
      (NPV) was 96.2%. The three-parameter combination predicted adverse clinical
      outcomes with a PPV of 54.5%, and a NPV of 94.1%. CT parameters including RV
      dysfunction were significantly associated with poor outcomes. Rapid risk
      stratification of patients with acute pulmonary embolism based on chest CT
      appears to be comparable with echocardiography, is clinically reliable, and may
      be useful in guiding management strategy.

PMID- 21717127
TI  - Direct medical care costs among pegylated interferon plus ribavirin-treated and
      untreated chronic hepatitis C patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a common and expensive infectious disease.
      The current standard of care for HCV infection, pegylated interferon with
      ribavirin (PEG-RBV), is costly and has a significant adverse event profile. AIM:
      To quantify the direct economic burden of HCV infection and PEG-RBV treatment for
      HCV. METHODS: Using a large administrative claims database, we evaluated the
      medical and prescription drug costs of patients with HCV from 2002 to 2007. A
      cohort of patients with PEG-RBV was 1:1 propensity score-matched to a cohort of
      untreated HCV patients. Multivariate models adjusted for demographic and clinical
      characteristics in evaluating the effect of PEG-RBV treatment on direct medical
      expenditure. RESULTS: The matched analysis included 20,002 patients. PEG-RBV
      treated patients had higher total direct medical costs ($28,547 vs. $21,752; P <
      0.001), outpatient pharmacy costs ($17,419 vs. $2,900; P < 0.001), and outpatient
      physician visit costs ($894 vs. $787; P < 0.001), but lower inpatient costs
      ($3,942 vs. $9,543; P < 0.001) and emergency room costs ($366 vs. $505; P <
      0.001). After multivariate adjustment, PEG-RBV use was associated with an
      additional $9,423 in total direct medical costs and an additional $12,244 in HCV
      related total medical costs. CONCLUSION: Total HCV-related medical costs are
      higher for treated than untreated patients, driven mostly by higher outpatient
      pharmacy costs, which outweigh higher HCV-related inpatient costs incurred by
      untreated patients.

PMID- 21717128
TI  - A stress and coping model of adjustment to caring for an adult with mental
      illness.
AB  - This study investigated the utility of a stress and coping framework for
      identifying factors associated with adjustment to informal caregiving to adults
      with mental illness. Relations between stress and coping predictors and negative
      (distress) and positive (positive affect, life satisfaction, benefit finding,
      health) carer adjustment outcomes were examined. A total of 114 caregivers
      completed questionnaires. Predictors included relevant background variables
      (carer and care recipient characteristics and caregiving context), coping
      resources (optimism, social support, carer-care recipient relationship quality),
      appraisal (threat, control, challenge) and coping strategies (problem-focused,
      avoidance, acceptance, meaning-focused). Results indicated that after controlling
      for relevant background variables (burden, caregiving frequency, care recipient
      symptom unpredictability), better caregiver adjustment was related to higher
      social support and optimism, better quality of carer-care recipient relationship,
      lower threat and higher challenge appraisals, and less reliance on avoidance
      coping, as hypothesised. Coping resources emerged as the most consistent
      predictor of adjustment. Findings support the utility of stress and coping theory
      in identifying risk and protective factors associated with adaptation to caring
      for an adult with mental illness.

PMID- 21717129
TI  - Effect of stocking density on growth and serum concentrations of thyroid hormones
      and cortisol in Amur sturgeon, Acipenser schrenckii.
AB  - This study investigated the effects of different stocking densities on growth and
      serum concentrations of thyroid hormones and cortisol in Amur sturgeon, Acipenser
      schrenckii. Fish were reared at low, medium, and high stocking densities (initial
      experimental densities were 0.30, 0.75, and 1.78 kg m(-2), respectively) for 70
      days. The results showed that high stocking density had negative effects on
      growth and feeding efficiency, and altered serum levels of thyroid hormones and
      cortisol in Amur sturgeon. A significant decrease in specific growth rate was
      observed as stocking density was increased. The feeding rate decreased
      significantly in the medium and high density groups, indicating that high
      stocking density reduced the food consumption of sturgeon. Food conversion ratio
      increased with increasing stocking density, suggesting that high stocking density
      might inhibit fish growth through decreasing food conversion efficiency. Serum
      concentrations of total triiodothyronine, free thyroxine, and free
      triiodothyronine were inversely related to stocking densities, whereas serum
      total thyroxine level of sturgeon stocked at different densities remained stable.
      Also, higher stocking density resulted in an elevation of serum cortisol level,
      indicating that the sturgeon stocked at the higher density experienced density
      dependent physiological stress. These results suggest growth suppression caused
      by high stocking density might be related to both crowding stress and the
      declines in peripheral circulating levels of thyroid hormones, as well as
      associated with the reductions in both food consumption and food conversion
      efficiency.

PMID- 21717130
TI  - Effects of chronic and periodic exposures to ammonia on the eye health in
      juvenile Atlantic halibut (Hippoglossus hippoglossus).
AB  - The effects of chronic and periodic peaks of un-ionised ammonia (UIA-N) exposure
      on eye health and cataract formation in juvenile Atlantic halibut, Hippoglossus
      hippoglossus, were examined. Fish with mean initial weight 51.7 g (SD 13.2) were
      exposed to five treatments consisting of control group and three groups
      (ChronicLow, ChronicMedium and ChronicHigh,) chronically exposed with UIA-N of
      0.06, 0.12 to 0.17 mg/l, respectively, for 62 days at 11.9 degrees C, pH 8.0 and
      salinity 340/00. Furthermore, a fifth group (HighPulse) was exposed to the same
      high levels as ChronicHigh for a short daily period (peak of 15 mg/l 30 min after
      exposure, 10 mg/l 1 h after exposure and 1.2 mg/l 3 h after exposure). In the
      subsequent period of the experimental study (from day 63 until day 100), no
      ammonia was added to the water. Mean weights were significantly lower in groups
      exposed to chronically high ambient ammonia concentrations compared to
      corresponding control group throughout the experimental period. The sampled fish
      exhibited signs of mild cataract formation, although the results showed no clear
      evidence that the ammonia treatments contributed to differences. Minor
      differences were found in measured muscle free amino acids, which could be used
      to explain potential changes in buffering capacity. The eye histidine status
      differed significantly at day 62, and osmotic differences in the eye lenses
      (measured as differences in N-acetyl histidine) were found in all group exposed
      to chronic levels of ammonia.

PMID- 21717131
TI  - Coffee consumption may influence hippocampal volume in young women.
AB  - Caffeine is the most often used psychoactive substance. Caffeine may influence
      neuroplasticity in animals. We investigated the relationship between caffeine
      intake (coffee consumption) and brain morphology. Forty-five healthy, non-smoking
      women aged 19-30 were included in the present study. We used semi-automatic user
      independent MR volumetry and voxel-based morphometry. We investigated the
      relationship between caffeine intake (coffee consumption) and the volumes of the
      cortical brain structures where caffeine is supposed to act. We found that high
      level and low-level caffeine intake was associated with a larger hippocampus
      compared to moderate-level caffeine intake. The other brain structures showed no
      association with coffee consumption or caffeine intake. The U-shape association
      between caffeine concentration and its effect has already been described in some
      experimental studies. To our knowledge this is one of the very first studies,
      which tries to find an association between brain morphology and coffee
      consumption or caffeine intake in humans using MR imaging.

PMID- 21717132
TI  - Comparative effects between bone marrow and mesenchymal stem cell transplantation
      in GDNF expression and motor function recovery in a motorneuron degenerative
      mouse model.
AB  - Motorneuron degenerative diseases, such as amyotrophic lateral sclerosis (ALS),
      are characterized by the progressive and rapid loss of motor neurons in the brain
      and spinal cord, leading to paralysis and death. GDNF (glial cell line derived
      neurotrophic factor) has been previously shown to be capable of protecting motor
      neurons in ALS animal models although its delivery to the spinal cord after
      systemic administration is blocked by the blood brain barrier. Thus, it is
      necessary to develop new neurotrophic approaches to protect these motor neurons
      from death. Bone marrow-derived stem cells have been shown to be capable of
      improving a large variety of neurodegenerative disorders through neurotrophic
      mediated mechanisms. Here we analyzed the effect of transplanting whole bone
      marrow or cultured mesenchymal stem cells into the spinal cord of a motor neuron
      degenerative mouse model. Motor functions were analyzed using various behavior
      tests for several weeks after transplantation. We observed that bone marrow, and
      to a lesser degree mesenchymal stem cell, treated mice improved significantly in
      the motor tests performed, coinciding with a higher GDNF immunoreactivity in the
      grafted spinal cord. In several cases, the treated spinal cords were extracted,
      the engrafted bone marrow cells isolated and cultured, and finally re
      transplanted into the spleen of immunodeficient mice. Re-grafted cells were
      detected in the host spleen, bloodstream and bone marrow, demonstrating a
      phenotypic stability. Thus, bone marrow cells do not suffer significant
      phenotypic modifications and is an efficient procedure to ameliorate motor-neuron
      degeneration, making it a possible therapeutic approach.

PMID- 21717133
TI  - Cancer-initiating enriched cell lines from human glioblastoma: preparing for drug
      discovery assays.
AB  - Glioblastoma multiforme (GBM) is the most lethal type of brain tumour in the
      adult humans. The cancer-initiating cell (CIC) hypothesis supports the notion
      that failures in current approaches to GBM treatment might be attributed to the
      survival of the CIC subpopulation. Recent evidence shows the idea that using CIC
      enriched cell lines derived from human GBM as new targets for drug discovery
      programs, may improve the chance of successfully translating the basic research
      findings into clinical trials. Although this approach appears promising, many
      important biological and technical issues (characterization of functional CIC
      markers, inter- and intra-tumoral CIC heterogeneity, and isolation and
      maintenance inconsistency) need to be resolved.

PMID- 21717134
TI  - Chronic hyperhomocysteinemia induces oxidative damage in the rat lung.
AB  - Tissue accumulation of homocysteine occurs in classical homocystinuria, a
      metabolic disease characterized biochemically by cystathionine beta-synthase
      deficiency. Vascular manifestations such as myocardial infarction, cerebral
      thrombosis, hepatic steatosis, and pulmonary embolism are common in this disease
      and poorly understood. In this study, we investigated the effect of chronic
      hyperhomocysteinemia on some parameters of oxidative stress (thiobarbituric acid
      reactive substances, protein carbonyl content, 2',7'-dichlorofluorescein
      fluorescence assay, and total radical-trapping antioxidant potent) and activities
      of antioxidant enzymes (superoxide dismutase, catalase, and glutathione
      peroxidase) in the rat lung. Reduced glutathione content and glucose 6-phosphate
      dehydrogenase activity, as well as nitrite levels, were also evaluated. Wistar
      rats received daily subcutaneous injections of Hcy (0.3-0.6 MUmol/g body weight)
      from the 6th to the 28th days-of-age and the control group received saline. One
      and 12 h after the last injection, rats were killed and the lungs collected.
      Hyperhomocysteinemia increased lipid peroxidation and oxidative damage to
      protein, and disrupted antioxidant defenses (enzymatic and non-enzymatic) in the
      lung of rats, characterizing a reliable oxidative stress. In contrast, this amino
      acid did not alter nitrite levels. Our findings showed a consistent profile of
      oxidative stress in the lung of rats, elicited by homocysteine, which could
      explain, at least in part, the mechanisms involved in the lung damage that is
      present in some homocystinuric patients.

PMID- 21717135
TI  - Variation in genotype and higher virulence of a strain of Sporothrix schenckii
      causing disseminated cutaneous sporotrichosis.
AB  - Sporotrichosis is usually a localized, lymphocutaneous disease, but its
      disseminated type was rarely reported. The main objective of this study was to
      identify specific DNA sequence variation and virulence of a strain of Sporothrix
      schenckii isolated from the lesion of disseminated cutaneous sporotrichosis. We
      confirmed this strain to be S. schenckii by((r)) tubulin and chitin synthase gene
      sequence analysis in addition to the routine mycological and partial ITS and NTS
      sequencing. We found a 10-bp deletion in the ribosomal NTS region of this strain,
      in reference to the sequence of control strains isolated from fixed cutaneous
      sporotrichosis. After inoculated into immunosuppressed mice, this strain caused
      more extensive system involvement and showed stronger virulence than the control
      strain isolated from a fixed cutaneous sporotrichosis. Our study thus suggests
      that different clinical manifestation of sporotrichosis may be associated with
      variation in genotype and virulence of the strain, independent of effects due to
      the immune status of the host.

PMID- 21717136
TI  - MR findings of lithium-related kidney disease: preliminary observations in four
      patients.
AB  - PURPOSE: To describe MR features of the kidney in patients on chronic lithium
      therapy and to correlate findings with the level of renal impairment. METHOD: In
      this retrospective HIPPA compliant study, a search was performed in our
      institutional clinical and radiological computerized database for subjects with
      lithium-related kidney disease between August 1, 2009 and May 30, 2010. Four
      patients (2 male and 2 females, mean age 64.75 +/- 3.5) with a total of eight
      kidneys fulfilled the search criteria. T2-weighted images were used to evaluate
      the presence, size, and distribution of renal cysts. T1-weighted images were used
      to evaluate kidney length, parenchymal thickness, and cortico-medullary
      differentiation (CMD). RESULTS: All kidneys displayed multiple, very abundant,
      small size (1-2 mm) cysts. The distribution of the cysts was symmetric in renal
      cortex and medulla and the number of cysts was similar in both kidneys. Sparse,
      asymmetrical parenchymal renal cysts >3 mm in diameter were also observed. The
      size and parenchyma thickness of both kidneys was considered normal in all
      patients. The CMD differentiation was preserved only in patients with normal
      laboratory kidney findings (n = 2), but was lost in patients with chronic renal
      failure. CONCLUSIONS: Multi-microcystic kidney disease secondary to long-term
      lithium therapy can be detected with MR imaging regardless of known renal
      impairment. Preservation of renal CMD was observed in both patients with normal
      kidney function. The results of our preliminary study suggest the possible role
      of MR imaging for the screening of early manifestations of nephropathy in
      patients undergoing chronic lithium therapy.

PMID- 21717137
TI  - Diagnosis of a variant of Mayer-Rokitansky-Kuster-Hauser syndrome: useful MRI
      findings.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome consists of vaginal aplasia
      associated with other mullerian duct abnormalities. Its penetrance varies, as
      does the involvement of other organ systems. Type I MRKU syndrome is
      characterized by an isolated absence of the proximal two thirds of the vagina,
      whereas type II is marked by other malformations which include vertebral,
      cardiac, urologic (upper tract), and otologic anomalies. In both types, the
      extent of vaginal aplasia varies, ranging from virtually absent to a length much
      more inferior than the normal one (2-5 cm). MRKU syndrome usually remains
      undetected until the patient presents with primary amenorrhea despite normal
      female sexual development. It is important to underline the fact that this
      syndrome is the second most common cause of primary amenorrhea. Although this
      condition has psychologically devastating consequences, its anatomical defects
      can be surgically treated. In fact, following diagnosis, surgery allows patients
      to have normal sexual function while reproduction may be possible if assisted
      techniques are performed.

PMID- 21717138
TI  - Is saliva suitable as a biological fluid in relative bioavailability studies?
      Analysis of its performance in a 4 x 2 replicate crossover design.
AB  - The aim of the present study was to evaluate the suitability of saliva as a
      biological fluid in relative bioavailability (RBA) studies, with the focus on the
      statistical design and data variability. A randomized, open-label, four periods
      and two sequences (4 * 2) crossover RBA study in saliva of two phenytoin (PHT)
      100 mg immediate-release capsules was performed. PHT is a narrow therapeutic
      index drug that has been widely used for epilepsy treatment for many years.
      Published information regarding its bioavailability is available, but plasma
      assessed. This study was designed and performed using saliva as the biological
      fluid and the simplest conditions that produce coherent results with previously
      published plasma studies. Pharmacokinetic parameters (C (max), T (max), AUC(0-t
      ), AUC(0-inf), C (max)/AUC(0-t ), K (e), and t (1/2)) for each volunteer at each
      period were calculated. Four different BE calculations were performed: individual
      bioequivalence, by the method of moments, and three average bioequivalence with
      data averaged over the two administrations and with data of periods 1-2 and 3-4.
      ANOVA calculation showed no significant subject-by-formulation interaction,
      period and sequence effects. The intra-subject variabilities were at least 20
      fold lower than the inter-subject ones for C (max), AUC(0-t ) and AUC(0-inf). In
      all four BE calculations, the 90% CIs for the T/R ratios of studied
      pharmacokinetics parameters fell within the 80-125% range proposed by most
      regulatory agencies.

PMID- 21717139
TI  - The effect of herbal medicine danshensu and ursolic acid on pharmacokinetics of
      rosuvastatin in rats.
AB  - The aim of this study was to explore potential herb-drug interaction between
      danshensu or ursolic acid and rosuvastatin. Compared to the control group given
      rosuvastatin alone, the concurrent use of danshensu (46 mg/kg) or ursolic acid
      (80 mg/kg) prior to the oral administration of rosuvastatin (100 mg/kg) increased
      the systemic exposure of rosuvastatin more than twofold. The plasma clearance of
      rosuvastatin was reduced to more than 57% in the presence of danshensu or ursolic
      acid. Rosuvastatin is minimally metabolized in the CYP2C9 isoenzyme pathway and
      to an even lesser extent in the CYP2C19 isoenzyme pathway. Rosuvastatin is a
      substrate of drug transporters such as human OATP1B1, OATP 1B3, OATP 1A2, BCRP
      and NTCP. Therefore, the present results suggested that the potential drug
      interaction between danshensu or ursolic acid and rosuvastatin may be mediated by
      one or more transporters (OATP1B1, OATP 1B3, OATP 1A2, BCRP and NTCP) and/or
      CYPs.

PMID- 21717140
TI  - Clinicopathological characteristics of ovarian carcinomas associated with
      endometriosis.
AB  - INTRODUCTION: Substantial histopathology data provide evidence that endometriosis
      might be viewed as a precursor lesion of endometrioid and clear cell carcinoma of
      the ovary, via intermediary atypical borderline lesions. Also, genes involved in
      both endometriosis and epithelial ovarian cancer have been shown to play a role
      in the pathogenesis of endometriosis-associated ovarian carcinoma. MATERIAL AND
      METHODS: A retrospective study of 17 cases of ovarian carcinomas associated with
      endometriosis, diagnosed between 2000 and 2009, at Aretaieion Hospital of
      University of Athens, is presented. 10/17 cases in this study (58.8%) were clear
      cell carcinomas (CCC), 6/17 cases (35.3%) were endometrioid adenocarcinomas (EAC)
      and 1/17 cases (5.9%) was a serous carcinoma associated with ovarian
      endometriosis. Patients's age was 27-76 years (mean age 58 years). Typical
      ovarian endometriosis was documented in 8/17 (47%) of the tumors. In 9/17 cases,
      areas of fibrosis or cystic lesions infiltrated by iron-laden macrophages and
      endometrial-like stroma, consistent with endometriosis, were observed.
      CONCLUSION: In comparison with common epithelial ovarian cancers, CCC and EACs of
      the ovary were presented at earlier stages. Cytoreductive surgical treatment is
      critical in order to plan appropriate post-operative management.

PMID- 21717141
TI  - Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in
      primary breast cancer patients.
AB  - PURPOSE: Isolated tumor cells (ITC) in the bone marrow of breast cancer patients
      increase the risk of recurrence and decrease survival, both at primary diagnosis
      and during follow-up. We tested the efficacy of trastuzumab in clearing HER2/neu
      positive ITC from the marrow of patients completing primary treatment. METHODS:
      Ten recurrence-free patients with persistent HER2/neu-positive ITC after routine
      adjuvant treatment received trastuzumab 6 mg/kg q3w for 12 months in a non
      randomized pilot phase II interventional study. Bone marrow ITC HER2/neu status
      was evaluated at baseline, after treatment for 3, 6 and 12 months, and yearly
      thereafter, in combination with clinical follow-up. Median follow-up was 23 (15
      64) months after baseline bone marrow aspiration. RESULTS: Trastuzumab for 12
      months eradicated HER2/neu-positive ITC from bone marrow in all patients (P =
      0.002) and significantly reduced the number of ITC-positive patients (P = 0.031).
      However, HER2/neu-negative ITC persisted in three patients immediately after
      treatment and were detected at yearly bone marrow aspiration in five patients.
      Two patients with ITC counts >=5 at yearly follow-up developed metastases and one
      died. CONCLUSION: This is the first evidence that trastuzumab is effective in
      clearing HER2/neu-positive cells from bone marrow during recurrence-free follow
      up in breast cancer patients. It also suggests, thanks to the antigen shift
      phenomenon, an important prognostic role for HER2/neu expression on marrow ITC as
      a real-time biopsy. However, treatment was mainly effective in patients with
      HER2/neu-positive ITC. Given the heterogeneity of minimal residual disease, these
      patients might benefit from a combination of targeted treatment approaches.

PMID- 21717142
TI  - Corynebacterium glutamicum RNase E/G-type endoribonuclease encoded by NCgl2281 is
      involved in the 5' maturation of 5S rRNA.
AB  - Corynebacterium glutamicum has one RNase E/G ortholog and one RNase J ortholog
      but no RNase Y. We previously reported that the C. glutamicum NCgl2281 gene
      encoding the RNase E/G ortholog complemented the rng::cat mutation in Escherichia
      coli but not the rne-1 mutation. In this study, we constructed an NCgl2281
      knockout mutant and found that the mutant cells accumulated 5S rRNA precursor
      molecules. The processing of 16S and 23S rRNA, tRNA, and tmRNA was normal. Primer
      extension analysis revealed that the RNase E/G ortholog cleaved at the -1 site of
      the 5' end of 5S rRNA. However, 3' maturation was essentially unaffected. These
      findings showed that C. glutamicum NCgl2281 endoribonuclease is involved in the
      5' maturation of 5S rRNA. This is the first report showing the physiological
      function of the RNase E/G ortholog in bacteria having one RNase E/G and one RNase
      J but no RNase Y.

PMID- 21717143
TI  - Efficient electron transfer from hydrogen to benzyl viologen by the [NiFe]
      hydrogenases of Escherichia coli is dependent on the coexpression of the iron
      sulfur cluster-containing small subunit.
AB  - Escherichia coli can both oxidize hydrogen and reduce protons. These activities
      involve three distinct [NiFe]-hydrogenases, termed Hyd-1, Hyd-2, and Hyd-3, each
      minimally comprising heterodimers of a large subunit, containing the [NiFe]
      active site, and a small subunit, bearing iron-sulfur clusters. Dihydrogen
      oxidizing activity can be determined using redox dyes like benzyl viologen (BV);
      however, it is unclear whether electron transfer to BV occurs directly at the
      active site, or via an iron-sulfur center in the small subunit. Plasmids encoding
      Strep-tagged derivatives of the large subunits of the three E. coli [NiFe]
      hydrogenases restored activity of the respective hydrogenase to strain FTD147,
      which carries in-frame deletions in the hyaB, hybC, and hycE genes encoding the
      large subunits of Hyd-1, Hyd-2, and Hyd-3, respectively. Purified Strep-HyaB was
      associated with the Hyd-1 small subunit (HyaA), and purified Strep-HybC was
      associated with the Hyd-2 small subunit (HybO), and a second iron-sulfur protein,
      HybA. However, Strep-HybC isolated from a hybO mutant had no other associated
      subunits and lacked BV-dependent hydrogenase activity. Mutants deleted separately
      for hyaA, hybO, or hycG (Hyd-3 small subunit) lacked BV-linked hydrogenase
      activity, despite the Hyd-1 and Hyd-2 large subunits being processed. These
      findings demonstrate that hydrogenase-dependent reduction of BV requires the
      small subunit.

PMID- 21717144
TI  - Comparative patterns of adrenal activity in captive and wild Canada lynx (Lynx
      canadensis).
AB  - Stress and animal well-being are often assessed using concentrations of
      glucocorticoids (GCs), a product of the hypothalamic-pituitary-adrenal axis.
      However, GC concentrations can also be modulated by predictable events, such as
      changes in season or life history stage. Understanding normative patterns of
      adrenal activity is critical for making valid conclusions about changes in GC
      concentrations. In this study, we validated an assay for monitoring fecal
      glucocorticoid metabolites (FGM) in Canada lynx. We then used this technique to
      assess patterns of adrenal activity in Canada lynx across several contexts. Our
      results show that captive lynx have higher FGM concentrations than wild lynx,
      which may be related to differences in stress levels, metabolic rate, diet, or
      body condition. We also found that FGM concentrations are correlated with
      reproductive status in females, but not in males. For males, seasonal increases
      in FGM expression coincide with the onset of the breeding season, whereas in
      females, FGM increase toward the end of the breeding season. This information
      provides a valuable foundation for making inferences about normative versus
      stress-induced changes in adrenal activity in Canada lynx.

PMID- 21717145
TI  - Pattern of asthma medication use among children from a large urban center in
      Brazil.
AB  - PURPOSE: Despite the advances in asthma therapeutics, there are few data on the
      use and determinants of anti-asthmatic drugs in the general population of
      children. This study describes the use of asthma medications among children in
      the general population and in children with current asthma, living in a large
      urban center in Brazil. METHODS: A population-based cross-sectional survey, aimed
      at analyzing asthma determinants, was conducted with 1,382 children aged 4-11
      years, between February and May 2006, in Salvador, Brazil. At baseline, an
      extensive questionnaire was applied, including questions about the use of asthma
      medications in the last 12 months. RESULTS: In all studied children (n = 1,382)
      aged 4-11 years, oral beta2-agonists were the drugs most frequently used (9.8%),
      followed by short-acting inhaled beta2-agonists (4.3%) and systemic
      corticosteroids (1.6%). Anti-asthmatic drug use was higher among males than
      females, and it significantly decreased with age in both genders. A total of 312
      children (22.6%) reported current asthma, and 62% of them were not being treated
      with any anti-asthmatic drugs. Of all those who reported following a certain type
      of treatment, 20% used oral beta2-agonists alone; 6.1%, short-acting inhaled
      beta2-agonists alone; and 4.8%, a combination of both drugs. Anti-asthmatic drug
      use did not differ according to socioeconomic status, except for the use of
      inhaled beta2-agonists and systemic corticosteroids. CONCLUSIONS: An overwhelming
      majority of asthmatic children were not using long-term medications for asthma,
      in particular inhaled corticosteroids, regardless of the severity of their
      disease. This result points to the deficiencies of the Brazilian public health
      system in recognizing this important pharmacological need for child care and
      thereby limiting the access of these children to a group of efficacious,
      available, and low risk therapeutic medications.

PMID- 21717146
TI  - Epidemiological, clinical, and diagnostic data on intestinal infections with
      Entamoeba histolytica and Entamoeba dispar among returning travelers.
AB  - BACKGROUND: Among travelers returning from the tropics, Entamoeba spp. are among
      the most frequently detected intestinal parasites, mainly the presumable
      apathogenic E. dispar and the pathogenic E. histolytica. METHODS: Among 5,378
      travelers seeking diagnosis and treatment for intestinal infections at the travel
      clinic of the University of Munich between 2005 and 2009, 103 laboratory
      confirmed amebiasis cases were detected. The study compares the results of
      various diagnostic tests among these patients, analyzes data on co-infections and
      clinical symptoms, and determines the risk for acquiring amebiasis. RESULTS:
      Initial screening tests (stool microscopy, coproantigen enzyme-linked
      immunosorbent assay [ELISA]) were positive in 82.5 and 93.9%, respectively. Fecal
      samples from patients with positive screening test results were subjected to
      polymerase chain reaction (PCR), which detected E. histolytica in 9.7% and E.
      dispar in 88.3% of the cases. The majority of E. histolytica cases and more than
      half of the E. dispar cases had intestinal symptoms typical for amebiasis. In
      53.4% of the cases, intestinal co-infections were found, mostly Blastocystis
      hominis (39.8%), Giardia lamblia (10.7%), Campylobacter spp. (4.9%), and
      Salmonella typhi (2.9%). The risk for travelers to be infected with E.
      histolytica or E. dispar was highest for destinations in West Africa, East
      Africa, and South and South-East Asia. CONCLUSION: Stool microscopy and
      coproantigen ELISA are appropriate screening tests for intestinal Entamoeba
      infections among travelers, but intestinal co-infections are common. PCR is
      highly recommended as the diagnostic method of choice for the differentiation of
      Entamoeba spp. The presumable apathogenic E. dispar seems to provoke intestinal
      symptoms.

PMID- 21717147
TI  - A rare cause of pulmonary infiltrates one should be aware of: a case of
      daptomycin-induced acute eosinophilic pneumonia.
AB  - We report a 69-year-old patient who developed fever and dyspnea 3 weeks after the
      initiation of daptomycin therapy for spondylodiscitis with lumbar epidural and
      bilateral psoas abscesses due to ampicillin- and high-level-gentamicin-resistant
      Enterococcus faecium. There was profound hypoxia and the chest X-ray showed
      extensive patchy infiltrates bilaterally. A bronchoalveolar lavage revealed 30%
      eosinophils and results of microbiological studies were normal. Daptomycin
      induced eosinophilic pneumonia was diagnosed and the patient rapidly improved
      after the discontinuation of daptomycin and a brief course of prednisone.
      Increased attention must be paid to this rare but serious side effect of
      daptomycin.

PMID- 21717148
TI  - Suspicion of viral gastroenteritis does improve compliance with hand hygiene.
AB  - PURPOSE: Viral gastroenteritis is common on pediatric wards, increasing the need
      for adherence with hand hygiene recommendations in order to prevent cross
      transmission. Therefore, we investigated hand hygiene reflecting complete work
      day activities on pediatric wards and focused on the influence of viral
      gastroenteritis. There are, so far, no studies representing complete working days
      on pediatric wards or addressing the influence of viral gastroenteritis. METHODS:
      This was a prospective, observational study (144 h in each group) on hand hygiene
      behavior in the care for children with and without suspected or proven viral
      gastroenteritis. RESULTS: We documented 40 and 30 hand hygiene opportunities per
      patient-day for ward-associated healthcare workers for children with and without
      viral gastroenteritis, respectively (P = 0.316). Healthcare workers' compliance
      with hand hygiene recommendations was significantly higher in children with viral
      gastroenteritis compared to those without, i.e., 72 versus 67% (P = 0.033),
      especially among physicians, being 92 versus 50% (P = 0.032). Compliance tended
      to be higher after patient contact than before, especially in the children with
      gastroenteritis (78 vs. 62%; P = 0.083). CONCLUSIONS: We conclude that viral
      gastroenteritis seemed to increase the number of daily opportunities for hand
      hygiene and did significantly increase compliance. In particular, this effect was
      seen after patient contact. Further research might address the awareness of
      undiagnosed transmissible diseases in order to prevent cross-transmissions.

PMID- 21717149
TI  - A national cross-sectional study on socio-behavioural factors that influence
      physicians' decisions to begin antimicrobial therapy.
AB  - PURPOSE: Current efforts to prevent antimicrobial resistance include limiting
      antimicrobial use, providing education about appropriate use, and developing
      better point-of-care tests, but what do physicians actually think of rational
      prescribing and potential interventions? We tried to ascertain which factors can
      influence a physician's decision to start antimicrobial therapy on a patient, and
      their opinions on measures to promote rational prescribing. METHODS: We conducted
      a nationwide, cross-sectional survey of 10,600 physicians from medical registries
      of all known board-certified physicians in Germany. RESULTS: Among respondents (n
      = 3,492; 33%; detailed non-response bias analysis included), 90% indicated that
      they decide to start antimicrobial therapy on a patient at least weekly, and 66%
      reported that they decide daily. We identified correlates for deciding to start
      antimicrobial therapy on a patient. Predictors were status as a hospital
      physician (odds ratio (OR) 1.29 (95% confidence interval (CI) 1.00-1.68)), male
      physician (OR 1.81 (95% CI 1.42-2.31)), being age 50-59 (OR 1.56 (95% CI 1.10
      2.21)), and practising in states in the former East Germany (OR 1.60 (95% CI 1.15
      2.21)). Each specialist was significantly less likely to decide to start a course
      of antimicrobial therapy than ENTs and urologists. Other predictors were agreeing
      to prescribe to be on the safe side (OR 1.34 (95% CI 1.03-1.76)), believing that
      the quality of prescribing practice improves after receiving continuing education
      from pharmaceutical companies (OR 1.43 (95% CI 1.11-1.84)), and having experience
      with failed therapy for resistant pathogens (OR 2.42 (95% CI 1.83-3.19)).
      CONCLUSIONS: Physicians in our sample decide to start antimicrobial therapy on a
      patient, and they value intervention to support prudent use, for example
      continuing education, practice guidelines and implementation of surveillance
      measures. Socio-behavioural factors, regional variation, gender, and age merit
      further research to promote rational antimicrobial prescribing and explore
      related influencing factors.

PMID- 21717150
TI  - Immunogenicity of two different hepatitis B vaccine schedules.

PMID- 21717151
TI  - A method for the analysis of 32 X chromosome insertion deletion polymorphisms in
      a single PCR.
AB  - Studies of human genetic variation predominantly use short tandem repeats (STRs)
      and single nucleotide polymorphisms (SNPs) but Insertion deletion polymorphisms
      (Indels) are being increasingly explored. They combine desirable characteristics
      of other genetic markers, especially the possibility of being analysed using
      short amplicon strategies, which increases the ease of analysis, contributing to
      justify their interest in population and forensic genetics. After the advent of
      autosomal and uniparental genomes (mtDNA and Y chromosome), these fields of
      research are also focusing on the X chromosome, given its special transmission
      pattern. The X chromosome markers brought new insights into the history of modern
      human populations and also proved useful in forensic kinship investigations,
      namely in deficient relationship cases and in cases where autosomes are
      uninformative. This work describes an X-Indel multiplex system amplifying 32
      biallelic markers in one single PCR. The multiplex includes X-Indels shown to be
      polymorphic in the major human population groups and follows a short amplicon
      strategy. The set was applied in the genetic characterization of sub-Saharan
      African, European and East Asian population samples and revealed high forensic
      efficiency, as measured by the accumulated power of discrimination (0.9999990 was
      the lowest value in males and 0.999999999998 was the highest in females) and mean
      exclusion chance varied between 0.998 and 0.9996 in duos and between 0.99997 and
      0.999998 in trios. Finally, a segregation analysis was performed using trio
      constellations of father-mother-daughters in order to address the transmission
      pattern and assess mutation rates of this type of markers.

PMID- 21717152
TI  - Development of 11 X-STR loci typing system and genetic analysis in Tibetan and
      Northern Han populations from China.
AB  - X-chromosomal short tandem repeats (X-STRs) loci are used for forensic practice
      in recent years which play increasingly important roles in some complex kinship
      cases. In this paper, a new multiplex polymerase chain reaction (PCR) system
      which can simultaneously analyze 11 X-STR markers (DXS8378, DXS6795, DXS7132,
      DXS6803, DXS9898, DXS6801, DXS7133, GATA165B12, HPRTB, DXS8377 and DXS7423) was
      developed. The samples of 1,605 (742 males and 863 females) unrelated individuals
      from Tibetan and Northern Han population were successfully analyzed using this
      multiplex system. A total of 103 alleles for all the loci were observed. Hardy
      Weinberg equilibrium tests demonstrated no significant deviation from expected
      values (P > 0.05) for all of the 11 X-STR loci in the two studied populations.
      Polymorphism information contents of the loci were 0.3864-0.9013, and powers of
      discrimination in females of the loci were 0.6317-0.9845. There were no
      statistically significant differences between Tibetan and Northern Han
      populations in allele distribution of the 11 X-STR loci, in line with analysis of
      molecular variance (AMOVA) results. Our work indicates that this multiplex system
      is useful for forensic analysis for the two populations in China.

PMID- 21717153
TI  - Allele and haplotype diversity of X-chromosomal STRs in Ivory Coast.
AB  - Twenty-one X-chromosomal short tandem repeat (STR) loci, including the six
      clusters of linked markers DXS10148-DXS10135-DXS8378 (Xp22), DXS7132-DXS10079
      DXS10074 (Xq12), DXS6801-DXS6809-DXS6789 (Xq21), DXS7424-DXS101 (Xq22), DXS10103
      HPRTB-DXS10101 (Xq26), DXS8377-DXS10146-DXS10134-DXS7423 (Xq28) and the loci
      DXS6800, GATA172D05 and DXS10011 were typed in a population sample from Ivory
      Coast (n=125; 51 men and 74 women). Allele and haplotype frequencies as well as
      linkage disequilibrium data for kinship calculations are provided. On the whole,
      no significant differences in the genetic variability of X-STR markers were
      observed between Ivorians and other sub-Saharan African populations belonging to
      the Niger-Kordofanian linguistic group.

PMID- 21717154
TI  - Comparison of three methods of DNA extraction from human bones with different
      degrees of degradation.
AB  - There is a necessity for deceased identification as a result of many accidents
      and sometimes bones are the only accessible source of DNA. So far, a universal
      method that allows for extraction of DNA from materials at different stages of
      degradation does not exist. The aims of this study were: the comparison of three
      methods of DNA extraction from bones with different degree of degradation and an
      evaluation of the usefulness of these methods in forensic genetics. The
      efficiency of DNA extraction, the degree of extract contamination by polymerase
      chain reaction (PCR) inhibitors and the possibility of determining the STR loci
      profile were especially being compared. Nuclear DNA from bones at different
      states of degradation was isolated using three methods: classical, organic phenol
      chloroform extraction, DNA extraction from crystal aggregates and extraction by
      total demineralisation. Total demineralisation is the best method for most cases
      of DNA extraction from bones, although it does not provide pure DNA. DNA
      extraction from aggregates removes inhibitors much better and is also a good
      method of choice when identity determination of exhumed remains is necessary. In
      the case of not buried bones (remains found outside) total demineralisation or
      phenol-chloroform protocols are more efficient for successful DNA extraction.

PMID- 21717155
TI  - Analysis of different medulloblastoma histotypes by two-dimensional gel and MALDI
      TOF.
AB  - OBJECTIVE: The purpose of this study is to detect different protein profiles in
      medulloblastoma (MDB) that may be clinically relevant and to check the
      correspondence of histological classification of MDB with proteomic profiles.
      MATERIALS AND METHODS: Surgical specimens, snap frozen at the time of
      neurosurgery, entered the proteomic study. Eight samples from patients (age
      range, 4 months-26 years) with different MDB histotypes (five classic, one
      desmoplastic/nodular, one with extensive nodularity, and one anaplastic) were
      analyzed by two-dimensional gel electrophoresis. One sample for each histotype
      was further characterized by matrix-assisted laser desorption/ionization time of
      flight mass spectrometry analysis. RESULTS: Eighty-six unique proteins were
      identified and compared to histology, with the determination of proteins
      expressed by single histotypes and of a smaller number of proteins shared by two
      or three histotypes. The sharp difference of protein expression was found to be
      in agreement with WHO histological classification, with the identification of
      type-specific proteins with limited overlapping between histotypes. CONCLUSION:
      Proteomic analysis confirmed and strengthened the difference between histotypes
      as biologically relevant. Cluster analysis enhanced the distance of extensive
      nodularity MDB from other histotypes. Possible innovative approaches to therapy
      may rely upon a proteomic-based classification of MDB tightly correlated to
      histology. The utility of snap freezing tumoral samples must be stressed and
      should become a mandatory task for pathologists.

PMID- 21717156
TI  - Synergistic anti-inflammatory effect of Radix Platycodon in combination with
      herbs for cleaning-heat and detoxification and its mechanism.
AB  - OBJECTIVE: To investigate the synergistic anti-inflammatory effect of Radix
      Platycodon in combination with herbs for cleaning-heat and detoxification and its
      mechanism for Fel-targeting. METHODS: Forty Wistar rats were randomly divided
      into five groups (8 per group): the sham-operated group, model group, Radix
      Platycodon group, Flos Lonicera and Fructus Forsythia (LF) group, and Radix
      Platycodon, Flos Lonicera and Fructus Forsythia combination (PLF) group, using a
      random number table. A rat chronic obstructive pulmonary disease (COPD) model was
      established by passive smoking and intratracheal instillation of
      lipopolysaccharide (LPS). The treatments started from the 15th day of passive
      smoking for a total duration of 14 days. At the end of the treatment, changes in
      the following measurements were determined: lung histopathology, inflammatory
      cytokines including tumor necrosis factor alpha (TNF-alpha), transforming growth
      factor beta (TGF-beta) and interleukin IL-1beta (IL-1beta) in bronchoalveolar
      lavage fluid (BALF), and mRNA expression of endogenous active substance
      intestinal trefoil factor 3 (TFF3) in the lung tissue. RESULTS: Light microscopy
      showed that compared with the sham-operated group, rats in the COPD model group
      had disrupted alveolar structure, collapsed local alveoli, significantly widened
      or even fused alveolar septa, and massive infiltration of inflammatory cells in
      the alveolar wall and interstitium. In addition, significant bronchial epithelium
      hyperplasia, partially shed epithelia, and marked inflammatory cell infiltration
      in the bronchial wall and its surrounding tissues were noticed. Electron
      microscopy showed that rats in the model group had degeneration of alveolar type
      II epithelial cell; reduction, breakage or even loss of cell surface microvilli;
      swollen mitochondria with disappearing cristae and vacuole-like structure; and,
      increased secondary lysosomes in alveolar macrophages. The TNF-alpha, TGF-beta
      and IL-1beta levels and white blood cell (WBC) count in BALF were significantly
      increased (P < 0.01 or P < 0.05) and TFF3 mRNA expression in the lung tissue was
      significantly reduced (P < 0.01). After treatment, the pathological morphology of
      lung injury was less severe in all three treatment groups. In addition, TGF-beta
      and IL-1beta and WBC count in BALF were decreased (P < 0.01 or P < 0.05), and
      TFF3 mRNA expression in the lung tissue was significantly increased in the PLF
      group (P < 0.01). Compared with the LF group, the IL-1beta in BALF was
      significantly decreased P < 0.05), and TFF3 mRNA expression was significantly
      increased (P < 0.05) in the PLF group. CONCLUSIONS: Radix Platycodon synergizes
      with herbs for cleaning-heat and detoxification in reducing inflammatory injury
      in a rat model of COPD. The synergistic anti-inflammatory effect is reflected in
      the improvement in pathological changes and in the reduction of IL-1beta levels
      in BALF. The mechanism of such synergistic action may be related to its effect on
      maintaining the TFF3 mRNA expression and Fel-targeting function.

PMID- 21717157
TI  - Effect of interstitial chemotherapy with ricin temperature-responsive gel for
      anti-breast cancer and immune regulation in rats.
AB  - OBJECTIVE: To explore the effect of ricin temperature response gel on breast
      cancer and its regulatory effect on immune function in rats. METHODS: Ricin was
      purified by chromatography and identified by immunoblotting. The rat
      subcutaneously transplanted breast cancer model was established. Forty model rats
      with a tumor diameter of about 3.0 cm were subjected to the study. They were
      randomized into four groups equally: the model group and three treated groups
      (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin
      temperature response gel via percutaneous intratumor injection, respectively. The
      tumor was isolated 10 days later for the estimation of tumor inhibition rate
      (TIR) by weighing, pathologic examination, and detection of tumor apoptosis
      associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral
      blood was obtained to test T-lymphocyte subsets, the killing function of
      lymphocytes, and the contents of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-2 (IL-2). The outcomes were compared between groups. RESULTS: The TIR
      in the ricin-gel group was 61.8%, with the pathologic examination showing
      extensive tumor tissue necrosis. Compared with the model group, after ricin
      temperature response gel treatment, bcl-2 expression was down-regulated, bax
      expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral
      blood were increased, the killing function of lymphocytes was enhanced, and the
      contents of TNF-alpha and IL-2 were elevated (P < 0.05 or P < 0.01). CONCLUSION:
      Intratumor injection of ricin temperature-responsive gel showed significant
      antitumor effect on breast cancer and could enhance the immune function in the
      tumor-bearing rat.

PMID- 21717158
TI  - Research progress on the standardization of Chinese Tuina therapy: a short
      review.
AB  - The standardization of Chinese Tuina therapy is one of the most popular research
      topics in Chinese medicine. By reviewing the literatures contributed by Chinese
      investigators between 1982 and 2010, the authors summarized the progress on
      Chinese Tuina manipulation techniques, in particular, focusing on the data on
      several key parameters (i.e., frequency, duration, and force). This summarization
      will benefit the standardization of Chinese Tuina.

PMID- 21717159
TI  - Study on the correlation between synaptic reconstruction and astrocyte after
      ischemia and the influence of electroacupuncture on rats.
AB  - OBJECTIVE: To observe the effects of electroacupuncture (EA) on the structure
      parameters of synapse and reactive changes of astrocyte in the marginal zone of
      focal cerebral ischemia in rats at different time zones so as to further explore
      its underlying mechanisms in the treatment of cerebral ischemia. METHODS: Ninety
      male Wistar rats were randomly assigned to sham-operation, model, and EA groups,
      with 30 animals in each group. Each group was subdivided into 1 h, as well as 1,
      3, 7, and 21 days post-operation groups, with 6 animals assigned to each time
      point subgroup. Heat coagulation-induced occlusion of the middle cerebral artery
      was performed to establish a model of focal cerebral ischemia. EA was applied
      immediately following surgery to the EA group [4/20 Hz, 2.0-3.0 V, 1-3 mA, to
      Baihui (GV20) and Dazhui (GV14)] for 30 min. Treatment was performed once a day,
      and experimental animals were sacrificed at 1 h, as well as 1, 3, 7 and 21 days
      postoperation. The ultrastructure changes in synapse and astrocytes were observed
      by using transmission electron microscopy. Glial fibrillary acidic protein (GFAP)
      expression and Ca(2+) of astrocytes were measured by using laser confocal
      scanning microscope. Excitatory amino acid transporters-2 (EAAT2) and connexin 43
      (CX43) expressions were assayed with immunohistochemical method. Canonical
      correlation analysis was conducted between structure parameters of synapse and
      parameters of astrocyte in the same time and group. RESULTS: Broken synapses were
      observed following cerebral ischemia, and the numbers of synapses were
      significantly decreased. Compared with the model group, synaptic ultrastructure
      was significantly improved in the EA group. Compared with the sham-operation
      group, synaptic number density was significantly decreased, as were postsynaptic
      density thickness, synaptic cleft width and synaptic interface curvature in the
      EA and model groups. However, compared with the model group, postsynaptic density
      thickness was significantly increased in the EA group at the same time points
      post-operation (P <0.05, P<0.01). In addition, synaptic cleft width, synaptic
      number density and synaptic interface curvature were significantly increased with
      the passage of time (P <0.05, P<0.01). The expression of GFAP in the EA group
      were significantly lower than those in the model group at all the time points (P
      <0.05, P<0.01). OD values of EAAT2 in the EA group were significantly higher than
      those in the model group at the same time (P <0.05, P<0.01). Compared with that
      in the model group, the expressions of CX43 in the EA group increased
      significantly at 3 days and 7 days (P <0.05, P<0.01). Ca(2+) average fluorescence
      intensity of astrocytes in the EA group was significantly lower than those in the
      model group at 1 h, 1 day, 3 days and 7 days (P <0.05, P<0.01). The changes in
      structure parameters of synapse were closely related to the changes of CX43,
      EAAT2, GFAP, Ca(2+) of astrocytes by EA treatment at all the time points.
      CONCLUSIONS: EA is helpful for synaptic reorganization, which may be related to
      its effect on intervening the activation state of astrocytes and promoting the
      beneficial interaction between astrocytes and synapses. Acupuncture could start
      the adjustment of neuron-glial network so as to promote the synaptic
      reorganization, which may be the key mechanism of treating cerebral ischemia.

PMID- 21717160
TI  - Effect of Wenhua Juanbi recipe on proliferation and apoptosis of synoviocytes in
      rats with collagen-inducing arthritis.
AB  - OBJECTIVE: To study the effect of Wenhua Juanbi Recipe (WJR) on proliferation and
      apoptosis of synoviocytes in rats with collagen-inducing arthritis (CIA).
      METHODS: A CIA model was induced by intradermal injection of bovine collagen type
      II emulsion at the base of rat tails. Thirty modeled healthy Wistar rats were
      randomly assigned to one of three groups (10 per group): the model group, the
      methotrexate (MTX)-treated group (0.78 mg/kg) and the WJR-treated group (22.9
      g/kg). A group of 10 healthy rats was used as normal control. Treatments or
      normal saline for the control group were administered by oral gavage once daily.
      Rats were sacrificed after 30-day treatment and subjected to the following
      examinations: arthritis index (AI) was estimated, inflammatory cell infiltration
      and proliferation in synovial membrane were evaluated by microscopy, the
      synoviocyte apoptosis was determined by TUNEL assay, and the cell apoptosis index
      was calculated. RESULTS: AI was lowered significantly in the WJR group compared
      to the model group (P<0.01). The pathological findings observed in the model
      group were reversed in the WJR group, including increase in inflammatory cell
      infiltration and synoviocyte proliferation in synovial membrane and reduction in
      cell apoptosis index (all P<0.01). CONCLUSIONS: Synoviocyte proliferation and
      apoptosis reduction were present in CIA rats. WJR was effective in treating the
      rat model of CIA. The therapeutic effect might be exerted through inducing
      apoptosis and suppressing proliferation of synoviocytes.

PMID- 21717161
TI  - Antiviral effects of aqueous extract from Spatholobus suberectus Dunn. against
      coxsackievirus B3 in mice.
AB  - OBJECTIVE: To investigate the antiviral effects of the aqueous extract of
      Spatholobus suberectus Dunn. (A.E.), a Chinese medicinal herb, against
      coxsackievirus B3 (CVB3). METHODS: The antiviral effects of A.E. against CVB3 in
      vitro (primarily cultured myocardial cells) and in vivo (BALB/c mice) were
      determined. Serum pharmacological method was also adopted by in vitro
      experiments. The effects of A.E. inhibiting the CVB3 mRNA expression were
      compared by RT-PCR in mice in vivo. RESULTS: A.E. exhibited obvious antiviral:
      effects in vivo, and serum samples obtained from the rats with oral
      administration of A.E. (10 MUg/mL, 5 MUg/mL), reduced the virus titers in the
      infected myocardial cells (3.00+/-0.70, 3.55+/-0.52, P<0.01). Meanwhile, the
      viral myocarditis induced by CVB3 was inhibited significantly by A.E., and the 15
      day mortality was reduced to 40% and 45% (P<0.01) in mice treated with A.E. at
      doses of 50 mg/kg and 100 mg/kg, respectively, while the 30-day mortality was
      decreased to 45% and 50%, respectively (P<0.01). Moreover, the mRNA expression of
      Coxsackie virus B3 was significantly inhibited by A.E. CONCLUSION: Aqueous
      extract of Spatholobus suberectus Dunn. (A.E.) has inhibitory effect on CVB3 both
      in vitro and in vivo.

PMID- 21717162
TI  - [MRI findings delay the diagnosis of nasopharyngeal carcinoma].
AB  - This report concerns a 55-year-old female patient who presented with headache,
      dry right eye and dry nose on the right side. After 5 months magnetic resonance
      imaging (MRI) was carried out but no pathological findings were diagnosed. Right
      sided facial pain appeared 6 months later and a second MRI was carried out but
      only fluid retention in the right mastoid was diagnosed. After a further 8 months
      paresis of the right abducent nerve occurred and a computed tomography (CT) scan
      of the petrous bone showed extensive destruction of the apex of the petrous
      pyramid. Subsequently a third MRI revealed a tumor of about 5 cm in diameter in
      the right pterygopalatine fossa which was also retrospectively visible in the
      first MRI with a size of approximately 3 cm and in the second MRI with 4 cm in
      diameter. The histological examination after biopsy resulted in the diagnosis of
      a nasopharyngeal carcinoma and radiochemotherapy was initiated. The patient died
      9 months later. The relatives of the patient applied to the arbitration board for
      medical liability which requested expert opinions in neuroradiology and
      otorhinolaryngology. The board came to the conclusion that the claims for damages
      against the radiologist who had made the three MRIs were well-founded and
      recommended an extrajudicial settlement.

PMID- 21717163
TI  - The role of Certified Registered Nurse Anesthetists in the United States.
AB  - Certified Registered Nurse Anesthetists (CRNAs) have been providing anesthesia
      care in the United States (US) for nearly 150 years. Historically, anesthesia
      care for surgical patients was mainly provided by trained nurses under the
      supervision of surgeons until the establishment of anesthesiology as a medical
      specialty in the US. Currently, all 50 US states utilize CRNAs to perform various
      kinds of anesthesia care, either under the medical supervision of
      anesthesiologists in most states, or independently without medical supervision in
      16 states; the latter has become an on-going source of conflict between
      anesthesiologists and CRNAs. Understanding the history and current conditions of
      anesthesia practice in the US is crucial for countries in which the shortage of
      anesthesia care providers has become a national issue.

PMID- 21717164
TI  - Encephalocraniocutaneous lipomatosis: a rare case with development of diffuse
      leptomeningeal lipomatosis during childhood.
AB  - We describe the uncommon development of leptomeningeal lipomatosis in a girl with
      encephalocraniocutaneous lipomatosis (ECCL). Leptomeningeal involvement had not
      been present at 2 years of age, but was demonstrated on CT and MRI at 10 years of
      age. Our case demonstrates follow-up neuroimaging features of ECCL that may be
      helpful to radiologists in suggesting the correct diagnosis, as ocular and
      cutaneous lesions may be non-specific clinically. The developmental nature of
      leptomeningeal involvement in our case suggests that close clinical and
      radiological follow-up is important in children with suspected or established
      ECCL.

PMID- 21717165
TI  - Paediatric cardiac CT examinations: impact of the iterative reconstruction method
      ASIR on image quality--preliminary findings.
AB  - BACKGROUND: Radiation dose exposure is of particular concern in children due to
      the possible harmful effects of ionizing radiation. The adaptive statistical
      iterative reconstruction (ASIR) method is a promising new technique that reduces
      image noise and produces better overall image quality compared with routine-dose
      contrast-enhanced methods. OBJECTIVE: To assess the benefits of ASIR on the
      diagnostic image quality in paediatric cardiac CT examinations. MATERIALS AND
      METHODS: Four paediatric radiologists based at two major hospitals evaluated ten
      low-dose paediatric cardiac examinations (80 kVp, CTDI(vol) 4.8-7.9 mGy, DLP 37.1
      178.9 mGy.cm). The average age of the cohort studied was 2.6 years (range 1 day
      to 7 years). Acquisitions were performed on a 64-MDCT scanner. All images were
      reconstructed at various ASIR percentages (0-100%). For each examination,
      radiologists scored 19 anatomical structures using the relative visual grading
      analysis method. To estimate the potential for dose reduction, acquisitions were
      also performed on a Catphan phantom and a paediatric phantom. RESULTS: The best
      image quality for all clinical images was obtained with 20% and 40% ASIR (p <
      0.001) whereas with ASIR above 50%, image quality significantly decreased (p <
      0.001). With 100% ASIR, a strong noise-free appearance of the structures reduced
      image conspicuity. A potential for dose reduction of about 36% is predicted for a
      2- to 3-year-old child when using 40% ASIR rather than the standard filtered back
      projection method. CONCLUSION: Reconstruction including 20% to 40% ASIR slightly
      improved the conspicuity of various paediatric cardiac structures in newborns and
      children with respect to conventional reconstruction (filtered back-projection)
      alone.

PMID- 21717166
TI  - Adolescent Kawasaki disease: usefulness of 64-slice CT coronary angiography for
      follow-up investigation.
AB  - BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis that mainly affects
      coronary arteries in children, and requires regular follow-up from the time of
      diagnosis. OBJECTIVE: To evaluate the feasibility of 64-slice CT angiography
      (CTA) for follow-up of patients with KD using previously performed invasive
      catheter coronary angiography (CCA) as reference standard. MATERIALS AND METHODS:
      The study group comprised 12 patients (age 17.6 +/- 2.9 years, mean +/- SD) with
      a diagnosis of KD and a previously performed CCA (interval, 32.6 +/- 13.5 months)
      who underwent 64-slice cardiac CTA. The quality of the images for establishing
      the presence of coronary abnormalities was determined by two observers. The CTA
      findings were compared with those from the prior CCA. RESULTS: Adequate image
      quality was obtained in all patients. Mean effective dose for CTA was 6.56 +/-
      0.95 mSv. CTA allowed accurate identification, characterization and measurement
      of all coronary aneurysms (n = 32), stenoses (n = 3) and occlusions (n = 9)
      previously demonstrated by CCA. One patient with disease progression went on to
      have percutaneous coronary intervention. CONCLUSION: Coronary lesions were
      reliably evaluated by 64-slice CTA in the follow-up of compliant patients with
      KD, reducing the need for repeated diagnostic invasive CCA. Hence, in an
      adequately selected patient population, the role of CCA could be limited almost
      only to therapeutic procedures.

PMID- 21717167
TI  - Uterus didelphys with unilateral vaginal atresia: multicystic dysplastic kidney
      is the precursor of "renal agenesis" and the key to early diagnosis of this
      genital anomaly.
AB  - BACKGROUND: Uterus didelphys with obstructed hemivagina (UDWOH) and ipsilateral
      renal agenesis is a distinct but rare entity. OBJECTIVE: To demonstrate the
      association between UDWOH and a multicystic dysplastic kidney (MCDK) in neonates.
      To demonstrate the usefulness of sonography with vaginal fluid instillation in
      the early and reliable diagnosis of this genital anomaly in girls with MCDK.
      MATERIALS AND METHODS: Our patients were five female neonates with a MCDK, which
      had been detected in utero. We performed sonography of the internal genitalia in
      all patients before and after filling the vagina with saline. RESULTS: In all
      five girls, sonographic examination revealed uterus didelphys with obstruction of
      the vagina ipsilateral to the MCDK. In three girls, a dilated ureter originating
      from the MCDK and extending to the level of the vagina could be clearly
      demonstrated, with one of these including the ureteric insertion into the atretic
      vagina. CONCLUSION: MCDK is key to the early diagnosis of UDWOH and will
      facilitate the provision of appropriate treatment. The neonatal period provides a
      unique opportunity for detecting uterine anomalies by sonography. An MCDK usually
      involutes and eventually mimics renal agenesis later in life.

PMID- 21717168
TI  - Size-exclusion chromatographic study of ECF and TCF softwood kraft pulp bleaching
      liquors.
AB  - BACKGROUND, AIMS, AND SCOPE: Currently, elemental chlorine-free (ECF) and totally
      chlorine-free (TCF) bleaching systems are widely used for pulp production. Low
      and medium molecular weight lignin break-down products are known to have harmful
      effects on the environment. According to some recent results, also high molecular
      weight (HMW) material consisting mainly of lignin and carbohydrates may cause
      toxic effects to the environment. For these reasons, toxicity and structure
      studies of HMW materials are of great importance. This investigation is a part of
      a larger project to obtain more structure information of HMW materials and
      toxicity of ECF and TCF bleaching effluents. Size-exclusion chromatography (SEC)
      has been commonly used for the characterization of organic macromolecules such as
      lignin, but to our knowledge, no reports have appeared dealing with the
      comparison of SEC of ECF and TCF bleaching liquors. The aim of the present study
      was to get more information about the molecular weight distribution (MWD) of HMW
      fractions of waste liquors from ECF and TCF bleaching sequences by SEC. METHODS:
      The MWDs of organic materials dissolved during different stages of ECF bleaching
      (O-D-EOP-D-ED) and TCF bleaching (O-Z-Q-P-Z-Q-P-P) of softwood (Pinus sylvestris)
      kraft pulp were determined and compared by SEC. All effluent samples from the
      above bleaching stages were ultrafiltrated using a membrane with a cutoff value
      of 1,000 Da. SEC was performed on high and also low molecular weight fractions
      and non-fractionated effluents. In the SEC experiments, a Superdex 75 column was
      used with 0.1 M NaOH solution as the eluent. Standards used for calibrating the
      SEC system were albumin, carboanhydrase, cytochrome C, tannic acid,
      dehydrodiacetovanillone, and vanillin. RESULTS AND DISCUSSION: The chromatograms
      of liquors from TCF bleaching stages vary more than those from ECF bleaching.
      Peroxide and chelating stages contained mostly high molecular weight (HMW) matter
      whereas chlorine dioxide and ozone stages had more low molecular weight
      compounds. The lignin content in HMW matter was higher than in stages that
      consisted of low molecular matter. Bleaching effluents contained the highest
      amounts of HMW material, mainly lignin, in the beginning of the sequences; the
      amounts decreased towards the end of the bleaching sequence. CONCLUSION:
      Determinations of MWD by the SEC method showed that effluents from the TCF
      sequence contained more HMW material than those from the ECF stage. This might be
      due to peroxide stages (P) that dissolve HMW lignin effectively. However, the
      molecular weights of ozone stages (Z) were very low compared to other stages.
      Chlorine dioxide stages also dissolved mostly low molecular weight lignin.
      Ultrafiltration of bleaching liquors showed that high molecular weight fraction
      also included some low molecular weight compounds and vice versa. High
      polydispersity and high lignin content correlated with the amount of HMW material
      in ECF and TCF bleaching stages. RECOMMENDATION AND OUTLOOK: Our liquor samples
      were studied by using a UV detector commonly used for lignin preparations; in
      upcoming investigations, it will be interesting to determine carbohydrates such
      as hemicelluloses. The results are applicable in papermaking in order to improve
      commonly used bleaching procedures, to test new potential bleaching systems, and
      to study chemical behavior of HMW materials in various bleaching liquors. The
      present results also form a good basis for toxicity measurements of ECF and TCF
      bleaching effluents and for more comprehensive spectroscopic and chromatographic
      experiments with samples taken from various bleaching stages. From the behavior
      of liquors studied, it appears that our other structure investigations by
      spectroscopic and chromatographic (NMR, Py-GC/MS, etc.) methods mostly correlate
      well with the present results.

PMID- 21717169
TI  - Surface ozone comparison conducted in two rural areas in central-southern Spain.
AB  - PURPOSE: The purpose of this work is to contribute to the understanding of the
      photochemical air pollution analysing the levels and temporal variations of
      surface ozone in two rural areas situated in central-southern Spain. METHOD: The
      study is based on ozone hourly data recorded during the overall period between
      January 2008 and November 2009. The seasonal and daily ozone cycles as well as
      the number of exceedances of the threshold established in the European Ozone
      Directive have been calculated and analysed. RESULTS: This study presents the
      first ozone data registered at these two rural sites in the Iberian Peninsula
      plateau. Ozone shows a clear seasonal variation with the lowest values in January
      and November. High ozone concentrations are interrelated with high radiation
      intensities, temperature and wind directions. The information threshold defined
      in the European Ozone Directives was exceeded six times, while the limit for
      protection of human health was exceeded more than 40 times. The limits to protect
      the vegetation were also exceeded. CONCLUSIONS: Porzuna (near Cabaneros National
      Park) presents higher ozone levels than Argamasilla during the night-time and
      during the daytime of the summer months. Ozone levels are lower in Argamasilla
      probably due to fresh emissions from the close industrial area of Puertollano.
      The ozone exceedances of the limits defined in the Ozone Directive point out an
      ozone problem in this rural region.

PMID- 21717170
TI  - Environmental risk assessment and concentration trend of atmospheric volatile
      organic compounds in Hyogo Prefecture, Japan.
AB  - PURPOSE: The purpose of this study was to evaluate the influences of volatile
      organic compounds (VOCs) emissions on hazardousness and photochemical reactivity
      and to propose efficient VOCs abatement strategies. METHODS: The atmospheric
      concentrations of 101 components of VOCs were measured at six sites which
      comprehend four urban areas, a roadside area, and an industrial area in Hyogo
      Prefecture. VOCs influence on hazardousness and photochemical reactivity were
      evaluated using VOCs measured data and the index on the health effect evaluation
      and ozone formation potential. The substances that require emissions reduction
      were selected from the evaluation results. The state and characteristics of
      environmental pollution were considered from the concentration trends of the
      selected substances. RESULTS: In industrial area, n-hexadecane, styrene, vinyl
      chloride monomer, and 1,2-dichloroethane showed a high concentration. In roadside
      area, n-hexane, n-undecane, n-dodecane, tetrachloroethylene, formaldehyde,
      acetaldehyde, and 1-butanol showed a high concentration. The excess cancer
      incidences for formaldehyde exceeded 10(-5) of the level of concern for
      carcinogenic effect at all sites. Toluene had a high percentage of ozone
      production. The interannual and seasonal trends of toluene concentrations were
      different at a regional level and the formaldehyde concentrations in summer were
      significantly higher than those in winter at the urban sites. CONCLUSIONS: The
      results show the need to prepare the emission reduction plan for the major
      sources such as vehicle exhaust, solvent use, and industrial processes to
      diminish the concentration of toluene that contributes significantly to the
      formation of photochemical oxidant.

PMID- 21717171
TI  - Plasma esterases in the tegu lizard Tupinambis merianae (Reptilia, Teiidae):
      impact of developmental stage, sex, and organophosphorus in vitro exposure.
AB  - PURPOSE: In this study, we determined normal serum butyrylcholinesterase (BChE)
      and carboxylesterase (CbE) activities in Tupinambis merianae in order to obtain
      reference values for organophosphorus pesticide monitoring. METHODS: Forty-two T.
      merianae individuals were grouped by sex and size to identify potential
      differences in their enzyme levels to allow for proper representation of normal
      values for females, males, juveniles, and hatchlings. Mean CbE was determined
      using two model substrates: alpha-naphtylacetate (alpha-NA) and p-nitrophenyl
      valerate (4-NPV). BChE and CbE sensitivity to malaoxon (Mx) was also evaluated as
      well as the possibility of BChE reactivation with pyridine-2-aldoxime
      methochloride (2-PAM). RESULTS: Mean adult females' BChE was significantly higher
      than adult males, juveniles, and hatchlings. No significant differences were
      found between groups regarding CbE. CbE (4-NPV) activity showed slightly negative
      correlation with lizard snout-vent length, while BChE and CbE (alpha-NA) showed
      no correlation with body size. Apparent IC(50) values for BChE and CbE (alpha-NA)
      suggested different sensitivities among groups. CbE (4-NPV) could not be
      inhibited. All Mx-inhibited groups treated with 2-PAM in a final concentration of
      2.8 mM showed clear signs of reactivation. CONCLUSIONS: In conclusion, the
      results demonstrate that (1) plasma esterase activity did not vary with age and
      sex, except for BChE activity, and (2) because biological and environmental
      variables could be confounding factors in the response of plasma cholinesterases,
      complementary biomarkers like CbE inhibition and oxime-induced reactivation of
      esterases are strongly recommended.

PMID- 21717172
TI  - Adsorption of adenine, cytosine, thymine, and uracil on sulfide-modified
      montmorillonite: FT-IR, Mossbauer and EPR spectroscopy and X-ray diffractometry
      studies.
AB  - In the present work the interactions of nucleic acid bases with and adsorption on
      clays were studied at two pHs (2.00, 7.00) using different techniques. As shown
      by Mossbauer and EPR spectroscopies and X-ray diffractometry, the most important
      finding of this work is that nucleic acid bases penetrate into the interlayer of
      the clays and oxidize Fe(2+) to Fe(3+), thus, this interaction cannot be regarded
      as a simple physical adsorption. For the two pHs the order of the adsorption of
      nucleic acid bases on the clays was: adenine ~ cytosine > thymine > uracil. The
      adsorption of adenine and cytosine on clays increased with decreasing of the pH.
      For unaltered montmorillonite this result could be explained by electrostatic
      forces between adenine/cytosine positively charged and clay negatively charged.
      However for montmorillonite modified with Na(2)S, probably van der Waals forces
      also play an important role since both adenine/cytosine and clay were positively
      charged. FT-IR spectra showed that the interaction between nucleic acid bases and
      clays was through NH(+) or NH (2) (+) groups. X-ray diffractograms showed that
      nucleic acid bases adsorbed on clays were distributed into the interlayer
      surface, edge sites and external surface functional groups (aluminol, silanol)
      EPR spectra showed that the intensity of the line g ~ 2 increased probably
      because the oxidation of Fe(2+) to Fe(3+) by nucleic acid bases and intensity of
      the line g = 4.1 increased due to the interaction of Fe(3+) with nucleic acid
      bases. Mossbauer spectra showed a large decreased on the Fe(2+) doublet area of
      the clays due to the reaction of nucleic acid bases with Fe(2+).

PMID- 21717173
TI  - Lack of association between intercellular adhesion molecule-1 (ICAM-1)
      polymorphisms and polycystic ovary syndrome.
AB  - PURPOSE: This study examined the possible association of G241R and K469E single
      nucleotide polymorphisms (SNPs) of ICAM-1 gene with the occurrence and
      clinical/biochemical characteristics of polycystic ovary syndrome (PCOS).
      METHODS: G241R and K469E SNPs in DNA from peripheral blood leukocytes of 169 PCOS
      and 259 healthy control women were investigated by real-time PCR combined with
      melting curve analysis using fluorescence-labeled hybridization probes. RESULTS:
      We did not find significant differences in the distributions of G241R and K469E
      polymorphisms, nor in the haplotype frequencies between PCOS and control women.
      None of the studied polymorphisms were found to affect insulin resistance indices
      significantly. CONCLUSIONS: These preliminary results suggest that the 241 and
      469 SNPs of ICAM-1 gene may not be risk factors for PCOS. Further studies with a
      larger cohort, analyzing other ICAM-1 polymorphisms are necessary to support our
      observations before any statement can be made about the relationship between PCOS
      and ICAM-1 polymorphisms.

PMID- 21717174
TI  - Attitudes of Klinefelter men and their relatives towards TESE-ICSI.
AB  - PURPOSE: At the start of the implementation of TESE-ICSI for Klinefelter men in
      the Netherlands, we aimed to evaluate their wish to father children and their
      attitudes towards this artificial reproduction technique. METHODS: Questionnaires
      were distributed to members of the Dutch Klinefelter Association (n = 365) and to
      Klinefelter cases known at our Department (n = 58). Questions addressed several
      aspects: socio-demographic characteristics, ascertainment of diagnosis, children
      and child wish, and TESE-ICSI. Data were characterized using descriptive
      statistics. RESULTS: A total of 260 questionnaires (corresponding to 194 cases,
      46%) were returned. A possible wish to father children was reported by 90% of
      Klinefelter men. 70% of Klinefelter men and 74% of their partners would
      (probably) opt for TESE-ICSI. CONCLUSION: The majority of Dutch Klinefelter men
      and their partners desire to have children and have a positive attitude towards
      TESE-ICSI. Concerns include the risk of congenital malformations/developmental
      delay of the child and the limited success rate of TESE-ICSI.

PMID- 21717175
TI  - Women with high telomerase activity in luteinised granulosa cells have a higher
      pregnancy rate during in vitro fertilisation treatment.
AB  - OBJECTIVE: To study the effect of telomerase activity (TA) in human luteinised
      granulosa cells (GCs) on the outcome of in vitro fertilisation treatment.
      METHODS: Fifty-six women, aged 23 to 39 years, were enrolled and divided into
      four groups according to their levels of TA. RESULTS: Seventeen cases in group A
      exhibited nondetectable TA, 16 cases in group B expressed low levels of TA
      (between 0.1 and 0.65 OD * mm), 14 cases in group C expressed moderate TA levels
      (between 0.66 and 1.00 OD * mm) and 9 cases in group D expressed high levels of
      TA (more than 1.00 OD * mm). The level of total serum testosterone (T) was
      significantly higher in groups C and D than in group A (1.43+/-0.10 vs. 1.08+/
      0.11 nmol/L, P<0.030 and 1.56+/-0.08 vs. 1.08+/-0.11 nmol/L, P<0.005,
      respectively). The TA level was positively correlated with T (r=0.291, P<0.011).
      No obvious differences were observed in rates of fertilisation, cleavage, mature
      oocyte formation or good-quality embryos among the groups. The patients in group
      D exhibited the highest rates of embryo implantation and clinical pregnancy (with
      rates of 52.63% and 77.78%, respectively, compared with 18.92% and 29.41% in
      group A, 25.71% and 37.50% in group B and 48% and 50% in group C, with P<0.018
      and P=0.112, respectively). The patients in group D also had a greater likelihood
      of becoming pregnant than those in group A (OR: 9.703, P < 0.023), group B (OR:
      14.765, P<0.009) or group C (OR: 5.560, P=0.103). CONCLUSIONS: Luteinised GCs
      have a certain potential for proliferation and TA of luteinised GCs may predict
      the clinical outcomes of IVF treatment. Some unknown regulatory mechanisms
      between TA and T should be studied in further trials.

PMID- 21717176
TI  - Cortical blindness caused by hypoxemia following an asthma attack.

PMID- 21717177
TI  - Infectious keratitis caused by fluoroquinolone-resistant Corynebacterium.

PMID- 21717178
TI  - The relation of functional visual acuity measurement methodology to tear
      functions and ocular surface status.
AB  - PURPOSE: To investigate the relation of functional visual acuity (FVA)
      measurements with dry eye test parameters and to compare the testing methods with
      and without blink suppression and anesthetic instillation. DESIGN: A prospective
      comparative case series. METHODS: Thirty right eyes of 30 dry eye patients and 25
      right eyes of 25 normal subjects seen at Keio University School of Medicine,
      Department of Ophthalmology were studied. FVA testing was performed using a FVA
      measurement system with two different approaches, one in which measurements were
      made under natural blinking conditions without topical anesthesia (FVA-N) and the
      other in which the measurements were made under the blink suppression condition
      with topical anesthetic eye drops (FVA-BS). Tear function examinations, such as
      the Schirmer test, tear film break-up time, and fluorescein and Rose Bengal vital
      staining as ocular surface evaluation, were performed. RESULTS: The mean logMAR
      FVA-N scores and logMAR Landolt visual acuity scores were significantly lower in
      the dry eye subjects than in the healthy controls (p < 0.05), while there were no
      statistical differences between the logMAR FVA-BS scores of the dry eye subjects
      and those of the healthy controls. There was a significant correlation between
      the logMAR Landolt visual acuities and the logMAR FVA-N and logMAR FVA-BS scores.
      The FVA-N scores correlated significantly with tear quantities, tear stability
      and, especially, the ocular surface vital staining scores. CONCLUSIONS: FVA
      measurements performed under natural blinking significantly reflected the tear
      functions and ocular surface status of the eye and would appear to be a reliable
      method of FVA testing. FVA measurement is also an accurate predictor of dry eye
      status.

PMID- 21717179
TI  - Uveal extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid
      tissue type with concomitant extraocular lesions in a Japanese man.

PMID- 21717180
TI  - The association of systemic disorders with Vogt-Koyanagi-Harada and sympathetic
      ophthalmia.
AB  - BACKGROUND: The aim of this work is to determine the systemic diseases and
      malignancy associated with Vogt-Koyanagi-Harada (VKH) disease compared to
      sympathetic ophthalmia (SO). METHODS: We conducted a retrospective comparative
      observational clinical study where the medical records of patients with the
      diagnosis of VKH and SO from 1999-2009 were reviewed. The study was carried out
      at the King Khaled Eye Specialist Hospital and The Eye Center in Riyadh, Saudi
      Arabia. Investigators recorded the age, gender, history of trauma, associated
      systemic disorders, and ocular and systemic manifestations. Patients were
      examined by an ophthalmologist as well as an internist. RESULTS: A total of 316
      patients were included: 256 patients had VKH and 60 patients had SO. The age
      range in the VKH group was 3-62 years with a mean age of 29 +/- 13 years. The age
      range in the SO group was 4-90 years with a mean age of 36 +/- 20 years. The mean
      follow-up period of patients with VKH was 58 +/- 50 months and patients with SO
      was 61 +/- 54 months. Out of 256 patients with VKH, there were 41 (16%) with
      systemic disorders. Comparatively, out of 60 patients with SO, no associated
      systemic autoimmune disorders or tumors were encountered. The difference between
      the VKH and SO groups was statistically significant (p = 0.003). CONCLUSIONS: VKH
      and SO are autoimmune disorders targeting melanin-bearing cells. Both diseases
      are characterized by immunologic dysregulation. We found a statistically
      significant association of systemic disorders and malignancy with VKH compared to
      SO. This finding may suggest that the two disorders may have different etiology
      with similar ocular and systemic manifestations.

PMID- 21717181
TI  - Dynamics of temporally interleaved percept-choice sequences: interaction via
      adaptation in shared neural populations.
AB  - At the onset of visually ambiguous or conflicting stimuli, our visual system
      quickly 'chooses' one of the possible percepts. Interrupted presentation of the
      same stimuli has revealed that each percept-choice depends strongly on the
      history of previous choices and the duration of the interruptions. Recent
      psychophysics and modeling has discovered increasingly rich dynamical structure
      in such percept-choice sequences, and explained or predicted these patterns in
      terms of simple neural mechanisms: fast cross-inhibition and slow shunting
      adaptation that also causes a near-threshold facilitatory effect. However, we
      still lack a clear understanding of the dynamical interactions between two
      distinct, temporally interleaved, percept-choice sequences-a type of experiment
      that probes which feature-level neural network connectivity and dynamics allow
      the visual system to resolve the vast ambiguity of everyday vision. Here, we fill
      this gap. We first show that a simple column-structured neural network captures
      the known phenomenology, and then identify and analyze the crucial underlying
      mechanism via two stages of model-reduction: A 6-population reduction shows how
      temporally well-separated sequences become coupled via adaptation in neurons that
      are shared between the populations driven by either of the two sequences. The
      essential dynamics can then be reduced further, to a set of iterated adaptation
      maps. This enables detailed analysis, resulting in the prediction of phase
      diagrams of possible sequence-pair patterns and their response to perturbations.
      These predictions invite a variety of future experiments.

PMID- 21717182
TI  - The growing role of bariatric surgery in the management of type 2 diabetes:
      evidences and open questions.
AB  - The use of bariatric surgery in the clinical management of type 2 diabetes has
      been recently endorsed in the clinical practice recommendations released by the
      most influential diabetologic associations. However, authoritative critic voices
      about the application of metabolic surgery in type 2 diabetes continue to appear
      in diabetologic literature. In this review, we will try therefore to understand
      what the reasons for this apparent dichotomy. In this paper, we revised what we
      believe are now clear evidences about the role of bariatric surgery in the
      treatment of type 2 diabetes in patients with morbid obesity: the efficacy of
      bariatric surgery in metabolic control, the existence of plausible weight
      independent metabolic mechanisms at least in some bariatric procedure, and the
      importance of the early referral to surgery in patients with firm indications.
      However, we stressed also the lack of clear high-quality long-term data about the
      effects of bariatric surgery in the prevention of both macro- and micro-vascular
      hard endpoints in patients with type 2 diabetes. The accrual of these results
      will be critical to completely clarify the risk/benefit ratio of bariatric
      surgery in diabetes, as compared to current pharmacologic therapies. This may be
      particularly important in patients in which data on long-term efficacy are still
      not completed, such as in patients with lower BMI levels.

PMID- 21717183
TI  - [Acute compartment syndrome of the lower leg due to knee arthroscopy].
AB  - This case report describes an acute postoperative compartment syndrome of the
      lower leg following simple arthroscopy of the knee. The diagnostics as well as
      the time course of further therapeutic procedures are considered critically.
      Furthermore, the surgical workflow is analyzed for possible reasons.
      Retrospectively, an accumulation of irrigation fluid passing through a popliteal
      cyst into the superficial flexor compartment must be suspected. In summary, even
      with an optimal perioperative management the subsequent compartment syndrome due
      to knee arthroscopy cannot be avoided with any certainty. However, immediate
      causal therapy lies in the urgent dermatofasciotomy to prevent irreversible
      neuromuscular damage.

PMID- 21717184
TI  - An efficient Agrobacterium-mediated transformation and regeneration system for
      leaf explants of two elite aspen hybrid clones Populus alba * P. berolinensis and
      Populus davidiana * P. bolleana.
AB  - Transgenic technology has been successfully used for gene function analyses and
      trait improvement in cereal plants. However, its usage is limited in woody
      plants, especially in the difficult-to-transform but commercially viable hybrid
      poplar. In this work, an efficient regeneration and transformation system was
      established for the production of two hybrid aspen clones: Populus alba * P.
      berolinensis and Populus davidiana * P. bolleana. A plant transformation vector
      designed to express the reporter gene uidA, encoding beta-glucuronidase (GUS),
      driven by the cauliflower mosaic virus 35S promoter, was used to detect
      transformation event at early stages of plant regeneration, and to optimize the
      parameters that may affect poplar transformation efficiency. Bacterium strain and
      age of leaf explant are two major factors that affect transformation efficiency.
      Addition of thidiazuron (TDZ) improved both regeneration and transformation
      efficiency. The transformation efficiency is approximately 9.3% for P. alba * P.
      berolinensis and 16.4% for P. davidiana * P. bolleana. Using this system,
      transgenic plants were usually produced in less than 1 month after co
      cultivation. The growth characteristics and morphology of transgenic plants were
      identical to the untransformed wild type plants, and the transgenes could be
      inherited by vegetative propagation, as confirmed by PCR, Southern blotting, RT
      PCR and beta-glucuronidase staining analyses. The establishment of this system
      will help to facilitate the studies of gene functions in tree growth and
      development at a genome level, and as well as the introduction of some valuable
      traits in aspen breeding.

PMID- 21717185
TI  - Overexpression of a resveratrol synthase gene (PcRS) from Polygonum cuspidatum in
      transgenic Arabidopsis causes the accumulation of trans-piceid with antifungal
      activity.
AB  - Although resveratrol-forming stilbene synthase (STS) genes have been well
      characterized in many plant species, there are only a few descriptions about STS
      genes from Polygonum cuspidatum Sieb. et Zucc, an important medicinal crop in
      Asian countries. To evaluate the biological functions of a Polygonum cuspidatum
      resveratrol synthase gene (PcRS), the PcRS gene was expressed in Arabidopsis
      under the control of Cauliflower mosaic virus (CaMV) 35S promoter. Integration
      and expression of transgene in the plant genome of Arabidopsis was confirmed by
      Southern blot and Northern blot analyses. Transgenic plants accumulated a new
      compound in both the leaves and seeds, which was identified as trans-piceid by
      high-pressure liquid chromatography (HPLC) and electrospray mass spectrometry
      (HPLC-ESI-MS). Overexpression of PcRS in transgenic Arabidopsis caused
      restriction of Colletotrichum higginsianum colonization by inhibition of spore
      production, resulting in enhanced resistance against C. higginsianum. So, the
      PcRS gene could be deployed in other crop plants to significantly enhance
      resistance to fungal pathogens and improve the nutritional quality. In addition,
      altered seed coat pigmentation and significant reduction in anthocyanin levels
      were observed in transgenic Arabidopsis, while the expression of endogenous
      chalcone synthase (CHS) gene was not down-regulated. These results suggest that
      additional STS activities cause a lack of precursors for CHS which leads to the
      disturbance of the subsequent flavonoid biosynthesis steps in Arabidopsis.

PMID- 21717186
TI  - Responses to magnetic stimuli recorded in peripheral nerves in the marine
      nudibranch mollusk Tritonia diomedea.
AB  - Prior behavioral and neurophysiological studies provide evidence that the
      nudibranch mollusk Tritonia orients to the earth's magnetic field. Earlier
      studies of electrophysiological responses in certain neurons of the brain to
      changing ambient magnetic fields suggest that although certain identified brain
      cells fire impulses when the ambient field is changed, these neuron somata and
      their central dentritic and axonal processes are themselves not primary magnetic
      receptors. Here, using semi-intact animal preparations from which the brain was
      removed, we recorded from peripheral nerve trunks. Using techniques to count
      spikes in individual nerves and separately also to identify, then count
      individual axonal spikes in extracellular records, we found both excitatory and
      inhibitory axonal responses elicited by changes in the direction of ambient earth
      strength magnetic fields. We found responses in nerves from many locations
      throughout the body and in axons innervating the body wall and rhinophores. Our
      results indicate that primary receptors for geomagnetism in Tritonia are not
      focally concentrated in any particular organ, but appear to be widely dispersed
      in the peripheral body tissues.

PMID- 21717187
TI  - Common vetch (Vicia sativa L.) germplasm: correlations of crude protein and
      mineral content to seed traits.
AB  - In order to increase knowledge of seed nutritive value and to demonstrate its
      relationship in common vetch (Vicia sativa L.) germplasm, 388 common vetch
      accessions were grown under field conditions in 2008-2009 growing season in Bursa
      province of Turkey. Seeds were analyzed for seed minerals (Ca, Cu, Mg, Mn, P, S,
      Zn and K) and crude protein (CP) content. The accessions were grouped according
      to testa and cotyledon color and seed size, and the results were evaluated by
      analysis of variance to determine relationships between minerals and CP content,
      testa and cotyledon colors, and seed weight. In general, there was no significant
      difference between testa colors or cotyledon colors in minerals and CP content.
      However, seed weight was closely associated with minerals and CP contents in this
      study. Analysis of variance and correlation analysis showed that seed weight was
      closely associated with some minerals and CP content. The small seeds had
      significantly higher Ca, Cu, Mg, Mn, S, Zn and CP contents than medium and large
      seeds.

PMID- 21717188
TI  - Host-dependent suppression of RNA silencing mediated by the viral suppressor p19
      in potato.
AB  - p19 protein encoded by tomato bushy stunt virus (TBSV) is known as a suppressor
      of RNA silencing via inhibition of small RNA-guided cleavage in plants. In this
      study, we generated TBSVp19-expressing patatin-RNAi transgenic potatoes to
      identify the inhibitory mechanisms of RNA silencing mediated by TBSVp19. In
      TBSVp19-expressing patatin-RNAi lines, reduction of patatin-derived siRNA
      accumulation and complementation of patatin transcripts were detected in
      comparison with the non-TBSVp19-expressing patatin-RNAi line, suggesting that
      TBSVp19 suppresses the siRNA-mediated silencing pathway. Interestingly, no
      apparent effect on the accumulation of miRNA168 and other miRNAs was detected in
      TBSVp19-expressing lines; previous studies reported that p19 induced the
      accumulation of both miRNA168 and its target Argonaute 1 (AGO1) mRNA, but
      suppressed AGO1 translation via up-regulation of miRNA168 in Arabidopsis. In
      addition, the expression of Argonaute 1 (AGO1-1 and AGO1-2) and Dicer-like 1
      (DCL1) was not significantly altered in p19-expressing lines. Interestingly, no
      translational inhibition of AGO1 mediated by p19 was detected. These results
      suggest that p19 suppresses siRNA-mediated silencing in potato, but may not
      affect miRNA-mediated silencing, possibly due to the host-dependent manner of p19
      activity.

PMID- 21717189
TI  - Rare sugar D-allose suppresses gibberellin signaling through hexokinase-dependent
      pathway in Oryza sativa L.
AB  - One of the rare sugars, D-allose, which is the epimer of D-glucose at C3, has an
      inhibitory effect on rice growth, but the molecular mechanisms of the growth
      inhibition by D-allose were unknown. The growth inhibition caused by D-allose was
      prevented by treatment with hexokinase inhibitors, D-mannoheptulose and N-acetyl
      D-glucosamine. Furthermore, the Arabidopsis glucose-insensitive2 (gin2) mutant,
      which is a loss-of-function mutant of the glucose sensor AtHXK1, showed a D
      allose-insensitive phenotype. D-Allose strongly inhibited the gibberellin
      dependent responses such as elongation of the second leaf sheath and induction of
      alpha-amylase in embryo-less half rice seeds. The growth of the slender rice1
      (slr1) mutant, which exhibits a constitutive gibberellin-responsive phenotype,
      was also inhibited by D-allose, and the growth inhibition of the slr1 mutant by D
      allose was also prevented by D-mannoheptulose treatment. The expressions of
      gibberellin-responsive genes were down-regulated by D-allose treatment, and the
      down-regulations of gibberellin-responsive genes were also prevented by D
      mannoheptulose treatment. These findings reveal that D-allose inhibits the
      gibberellin-signaling through a hexokinase-dependent pathway.

PMID- 21717190
TI  - Chemosensory function assessed with psychophysical testing and event-related
      potentials in patients with atrophic rhinitis.
AB  - Atrophic rhinitis (AR) is a chronic inflammation of the nose characterized by an
      atrophy of the nasal mucosa. This is typically associated with an impaired sense
      of smell and a subjective sensation of poor nasal breathing. The aim of this
      study is to assess chemosensory function in patients suffering from AR using
      psychophysical testings and event-related potentials (ERP) responses. A cohort of
      nine patients was extensively studied. Eight out of nine had secondary AR sequela
      of a bilateral total inferior turbinectomy whereas one patient had a primary AR.
      All the patients had a clinical evaluation using Sniffin' Sticks test and a retro
      olfaction test and an electrophysiological evaluation based upon ERPs obtained
      after both olfactory and trigeminal stimuli. All the patients complained of a
      poor nasal breathing and presented a distortion of the chemosensory function.
      Actually, the orthonasal psychophysical testing showed that four patients out of
      nine had anosmia, three out of nine had hyposmia and two out of nine were
      normosmic. All the patients demonstrated retro-olfaction scores inferior to the
      normal values. The chemosensory ERP showed that seven patients had no olfactory
      response whereas six had no trigeminal response. Four patients had neither
      olfactory nor trigeminal ERP response. In conclusion, this study demonstrates
      that most patients with AR secondary to a total bilateral inferior turbinectomy
      have a reduction of the chemosensory function measured objectively by
      psychophysical testings and ERP [corrected].

PMID- 21717191
TI  - Underexpression of TIM-3 and blunted galectin-9-induced apoptosis of CD4+ T cells
      in rheumatoid arthritis.
AB  - The aim of this study is to compare the expression of TIM-3 from CD4+ T cells
      from rheumatoid arthritis (RA) patients and healthy controls and to evaluate the
      effect of galectin-9 (Gal-9) on apoptosis of CD4+ T cells in these patients. CD4+
      T cells from RA patients and healthy controls were isolated from peripheral blood
      mononuclear cells and were activated. The expression of TIM-3 mRNA in CD4+ T
      cells was measured using real-time polymerase chain reaction. CD4+ T cells were
      activated in the presence of graded doses of Gal-9 or control, and Gal-9-induced
      cytotoxicity and apoptotic activity of CD4+ T cells were analyzed using MTT
      assays and annexin-V staining, respectively. TIM-3 mRNA expression was
      significantly lower in CD4+ T cells from RA patients compared with those in
      healthy controls (p = 0.028). CD4+ T cell survival as measured by MTT assay when
      incubated with Gal-9 (15 nM) was significantly higher in RA patients than in
      healthy controls (p = 0.002). Apoptotic activity of CD4+ T cells from healthy
      controls as measured by annexin staining increased with graded doses of Gal-9 (0
      nM vs. 30 nM, 0 nM vs. 90 nM, p = 0.016 each). However, apoptotic activity of
      CD4+ T cells from RA patients did not change despite the stimulation with Gal-9.
      Gal-9-mediated apoptosis of CD4+ T cells is dysfunctional in RA patients. Blunted
      Gal-9-mediated apoptosis may be exerted through underexpression of TIM-3 that
      negatively regulates Th1 response. Our data suggest that TIM-3 and its
      interaction with Gal-9 may play an important role in the pathogenesis of RA and
      may represent a potential therapeutic target.

PMID- 21717192
TI  - Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro
      and in vivo through the upregulation of Bax and Fas/FasL and downregulation of
      Bcl-2.
AB  - PURPOSE: Matrine, one of the main active components of extracts from the dry
      roots of Sophora flavescens, has potent anti-tumor activity in various cancer
      cell lines. However, the activity of matrine against osteosarcoma remains
      unclear. In the present study, we examined the effects of matrine on human
      osteosarcoma cells and explored the underlying mechanism. METHODS: Four human
      osteosarcoma cell lines: MG-63, U-2OS, Saos-2, and MNNG/HOS were treated by
      matrine and subjected to MTT assay, annexin V-FITC/PI double staining, and TUNEL
      assay. The activation of caspases and the expression of pro-apoptotic and anti
      apoptotic factors were examined by qRT-PCR and Western blot. In addition,
      MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and
      matrine was intraperitoneally (i.p.) administered to evaluate the anti-cancer
      capacity of matrine in vivo. RESULTS: We found that matrine inhibited the
      proliferation and induced apoptosis of the four osteosarcoma cell lines in vitro
      and induced the activation of caspase-3, -8, and -9 in a dose-dependent manner.
      Furthermore, the pro-apoptotic factors Bax and Fas/FasL were upregulated, and the
      anti-apoptotic Bcl-2 was downregulated. More importantly our in vivo, studies
      showed that administration of matrine decreased tumor growth in a dose-dependent
      manner. Immunohistochemistry analysis demonstrated the downregulation of Bcl-2
      and upregulation of Bax and Fas/FasL in MNNG/HOS tumor tissues following matrine
      treatment, consistent with the in vitro results. CONCLUSION: Our results
      demonstrate that matrine inhibits the proliferation and induces apoptosis of
      human osteosarcoma cells in vitro and in vivo. The induction of apoptosis appears
      to occur through the upregulation of Fas/FasL and Bax, downregulation of Bcl-2,
      and activation of caspase-3, -8, and -9, which then trigger major apoptotic
      cascades.

PMID- 21717193
TI  - The clinical and radiological spectrum of posterior reversible encephalopathy
      syndrome: the retrospective Berlin PRES study.
AB  - The aim of the study was to characterize the clinical and radiological spectrum
      of posterior reversible encephalopathy syndrome (PRES) in a large cohort. The
      radiological report data bases of the authors' university hospitals were searched
      for patients with PRES. Various imaging features at onset of symptoms and on
      follow-up as well as clinical and paraclinical data were tabulated in those
      patients fulfilling the criteria for PRES. Exploratory univariate analyses were
      performed. A total of 96 patients with PRES were included into the study. Wide
      differences in lesion location, diffusivity, distribution pattern, edema
      severity, hemorrhage, underlying diseases, symptoms, mean arterial pressure (MAP)
      and coagulation status were encountered. Hemorrhage occurred significantly more
      frequently in patients with altered coagulation state and was significantly
      associated with higher edema grades and with the presence of cytotoxic edema.
      There was a significant difference in MAP between toxic associations with higher
      MAP in infection, eclampsy and autoimmune disorders, while lower MAP was found in
      chemotherapy and immunsupression. In 82% of patients complete or near complete
      resolution of edema was noted during follow-up. Higher MAP levels were associated
      with incomplete edema resolution. In 43% of patients residual lesions were seen
      with a relatively even distribution between focal gliosis, infarction,
      posthemorrhagic residua, atrophy and laminar necrosis. PRES in this large
      hospital-based retrospective study comprises a wide radiological and clinical
      spectrum. Residual lesions were encountered more frequently than commonly
      expected. Our results point towards a differential contribution of high blood
      pressure to the course of PRES in different underlying etiologies.

PMID- 21717194
TI  - The pedunculopontine nucleus is related to visual hallucinations in Parkinson's
      disease: preliminary results of a voxel-based morphometry study.
AB  - Visual hallucinations (VH) are common in Parkinson's disease (PD) and lead to a
      poor quality of life. For a long time, dopaminergic therapy was considered to be
      the most important risk factor for the development of VH in PD. Recently, the
      cholinergic system, including the pedunculopontine nucleus (PPN), has been
      implicated in the pathophysiology of VH. The aim of the present study was to
      investigate grey matter density of the PPN region and one of its projection
      areas, the thalamus. Thirteen non-demented PD patients with VH were compared to
      16 non-demented PD patients without VH, 13 demented PD patients (PDD) with VH and
      11 patients with dementia with Lewy bodies (DLB). Isotropic 3-D T1-weighted MRI
      images (3T) were analysed using voxel-based morphometry (VBM) with the PPN region
      and thalamus as ROIs. PD and PDD patients with VH showed grey matter reductions
      of the PPN region and the thalamus compared to PD patients without VH. VH in
      PD(D) patients are associated with atrophy of the PPN region and its thalamic
      target area, suggesting that a cholinergic deficit may be involved in the
      development of VH in PD(D).

PMID- 21717195
TI  - Social inequalities or inequities in cancer incidence? Repeated census-cancer
      cohort studies, New Zealand 1981-1986 to 2001-2004.
AB  - BACKGROUND: We examine incidence trends for 18 adult cancers, by ethnicity and
      socioeconomic position in New Zealand. METHODS: The 1981 to 2001 censuses were
      linked to subsequent cancer registrations, giving 47.5 million person-years of
      follow-up. RESULTS ETHNICITY: Pooled over time, differences were marked: Pacific
      and Maori rates of cervical, endometrial, stomach and pancreatic cancers were 1.5
      2.5 times European/Other rates; Maori, Pacific and Asian rates of liver cancer
      were 5 times European/Other; European/Other rates of colorectal, bladder and
      brain cancers were 1.5-2 times the rates of other groups and melanoma rates 5-10
      times higher; Pacific and Asian kidney cancer rates were half those of Maori and
      European/Other. Over time, Maori and Pacific rates of cervical cancer fell faster
      and Maori rates of colorectal and breast cancer increased faster, than
      European/Other rates. Male lung cancer rates decreased for European/Other, were
      stable for Maori and increased for Pacific. Female lung cancer rates increased
      for all ethnic groups. INCOME: Other than lung (rate ratio 1.35 men, 1.56 women),
      cervical (1.35) and stomach cancer (1.23), differences in incidence by income
      were modest or absent. CONCLUSIONS: Tobacco explains many of the social group
      trends and differences and constitutes an inequity. Cervical cancer trends are
      plausibly explained by screening and sexual practices. Faster increases of
      colorectal and breast cancer among Maori are presumably due to changes in dietary
      and reproductive behaviour, but the higher Maori breast cancer rate is
      unexplained. Ethnic differences in bladder, brain, endometrial and kidney cancer
      cannot be fully explained.

PMID- 21717196
TI  - Human immunoglobulin G levels of viruses and associated glioma risk.
AB  - Few consistent etiological factors have been identified for primary brain tumors.
      Inverse associations to asthma and low levels of varicella-zoster virus,
      immunoglobulin (Ig) levels in prevalent cases have indicted a role for the immune
      system in the development of glioma. Because samples from prevalent cases of
      glioma could be influenced by treatments such as steroids and chemotherapy, we
      investigated pre-diagnostic samples from three large Scandinavian cohorts. To
      test the hypothesis that immune response levels to these viruses are associated
      etiologically with glioma risk, we investigated pre-diagnostic immunoglobulin
      levels for cytomegalovirus (CMV), varicella-zoster virus (VZV), adenovirus (Ad),
      and Epstein-Barr virus (EBV) including the nuclear antigen (EBNA1) using plasma
      samples from 197 cases of adult glioma and 394 controls collected from population
      based cohorts in Sweden and Denmark. Low VZV IgG levels were marginally
      significantly more common in glioma cases than the controls (odds ratio (OR) =
      0.68, 95% CI 0.41-1.13) for the fourth compared with the first quartile (p = 0.06
      for trend). These results were more prominent when analyzing cases with blood
      sampling at least 2 years before diagnosis (OR = 0.63, 95% CI 0.37-1.08) (p =
      0.03). No association with glioma risk was observed for CMV, EBV, and adenovirus.

PMID- 21717197
TI  - The effect of changes of model for end-stage liver disease score during waiting
      time on post-liver transplant mortality.
AB  - OBJECTIVE: Model for End-Stage Liver Disease (MELD) score is found to be a robust
      predictor of mortality while on waiting list for liver transplantation. However,
      studies have shown inconsistent results for transplant MELD as a predictor of
      posttransplant mortality. AIM: To find whether utilization of MELD at listing, at
      transplant, or Delta MELD while waiting can predict outcome at a national
      transplant center, which is not part of an organ sharing network. METHOD:
      Retrospective analysis of patients listed for liver transplantation at the New
      Zealand Liver Transplant Unit (NZLTU) with calculation of MELD score at the time
      of listing and at transplant with/without adjustment points for hepatocellular
      carcinoma (HCC). RESULTS: Between 1998 and 2005, 264 adult patients were listed
      for liver transplantation. Median age at transplant was 49 years (range 16-70)
      and 65% were male. The most common etiology was viral hepatitis (50%). A total of
      48 patients (20%) had known HCC. MELD scores (adjusted and nonadjusted) at
      listing and at transplantation were similar across all primary liver diseases (P
      = 0.88, 0.93, respectively). Adjusted MELD scores were significantly higher in
      patients listed for HCC compared to those without HCC (P < 0.001; hazard ratio
      1.33; 95% confidence interval = 1.21-1.46). MELD scores at transplant did not
      correlate with either 3 or 12 months mortality (P = 0.336, 0.228, respectively).
      This finding was consistent whether the change of MELD during waiting time was >1
      point or less (P = 0.67). Waiting time does not appear to influence
      posttransplant survival (P = 0.75). CONCLUSION: In a country with a single
      transplant center and organ retrieval organization, the addition of MELD score to
      current minimal listing criteria does not improve prioritization of patients on
      the waiting list or predict posttransplant survival. Also, adjusting MELD score
      for HCC would unfairly disadvantage patients listed without HCC.

PMID- 21717198
TI  - Dabigatran in atrial fibrillation: pharmacology and clinical trials.
AB  - The central pharmacologic approach to stroke prevention in atrial fibrillation
      has recently changed with the approval of dabigatran by the US Food and Drug
      Administration (FDA). Dabigatran is an oral anticoagulant that belongs to the
      class of direct thrombin inhibitors. Dabigatran has predictable pharmacokinetics,
      without significant drug and food interactions, rapid onset, and requires twice
      daily administration without the need for monitoring. The only drug
      contraindicated with dabigatran is rifampin. In the Randomized Evaluation of Long
      Term Anticoagulation Therapy (RE-LY) trial, dabigatran at a dose of 150 mg bid is
      statistically superior to warfarin in preventing strokes and systemic embolism in
      patients with atrial fibrillation and has a lower non-statistically significant
      rate of major bleeding. There is significantly lower rate of intracranial
      bleeding. The FDA recently approved the 150-mg bid dose for patients with a
      creatinine clearance above 30 mL/min and 75 mg bid for use in patients with a
      creatinine clearance of 15 to 30 mL/min. A prespecified subanalysis in both
      warfarin-experienced and warfarin-naive subgroups mirrored the main results. For
      cardioversions, a post hoc analysis showed that the rate of thromboembolism and
      major bleeding within 30 days of cardioversion for dabigatran 150 mg bid was low
      and comparable to that of warfarin, with or without transesophageal
      echocardiography guidance. Dabigatran, therefore, is the first novel
      anticoagulant to offer an alternative to warfarin.

PMID- 21717199
TI  - Sex differences in short- and long-term case-fatality of myocardial infarction.
AB  - Declining trends in case fatality (CF) of MI events have been generally reported
      in western countries. It is, however, not clear whether the development has been
      equally beneficial in both sexes. Data from two large population based registers,
      FINAMI and the Finnish National Cardiovascular Disease Register (CVDR) were used
      to determine whether the CF of incident MI events has declined less in women than
      in men. All patients aged 35 and over were included. CF was calculated for
      different time periods after the onset of the MI event, the main emphasis was in
      pre-hospital, 28-day, and 1-year CF. Figures were compared between two study
      periods: 1994-1996 and 2000-2002. A total of 6,342 incident MI events were
      recorded in FINAMI and 117,632 events in CVDR during the study periods.
      Comparison between the two study periods showed that the CF was generally
      declining. However, a slower decline in short-term CF was seen among young
      (aged<55 years) women (P for sex by study period interaction in pre-hospital
      CF=0.028 in FINAMI and 0.003 in CVDR, and for 28-day CF P=0.016 in FINAMI and
      <0.0001 in CVDR). In conclusion, the short and long-term prognosis of MI events
      has improved in both sexes. Pre-hospital CF has declined less among younger women
      than among men and among older women. This slower decline in early CF was
      responsible for the slower improvement in 28-day and 1-year prognosis in young
      women.

PMID- 21717200
TI  - Nomogram predicting clinical outcomes in breast cancer patients treated with
      neoadjuvant chemotherapy.
AB  - PURPOSE: The aim of this study was to combine clinical pathologic variables that
      are associated with pathologic completer response (pCR) and relapse-free survival
      (RFS) after neoadjuvant chemotherapy into prediction nomograms. METHODS: A total
      of 370 stage II or III breast cancer patients who received neoadjuvant
      docetaxel/doxorubicin chemotherapy were enrolled in this study. We developed the
      nomograms using logistic regression model for pCR and Cox proportional hazard
      regression model for RFS. RESULTS: The nomogram for pCR based on initial tumor
      size, estrogen receptor (ER), human epidermal growth factor receptor 2, and Ki67
      had good discrimination performance (AUROC = 0.830). Multivariate Cox model
      identified age less than 35, initial clinical stage, pathologic stage, ER, Ki67
      as prognostic factors, and the nomogram for RFS was developed based on these
      covariates. The concordance index for the second nomogram was 0.781, and
      calibration was also good. CONCLUSIONS: We developed nomograms based on clinical
      and pathologic characteristics to predict the probability of pCR and RFS for
      patients receiving neoadjuvant docetaxel/doxorubicin chemotherapy.

PMID- 21717201
TI  - Anterolateral approach for mini-open rotator cuff repair.
AB  - PURPOSE: This study was undertaken to introduce an anterolateral approach for
      mini-open rotator cuff repair and evaluate its clinical outcome and
      effectiveness. METHODS: We evaluated 128 consecutive cases that were repaired by
      mini-open repair using an anterolateral approach. There were 80 men and 48 women,
      with an average age of 56.2 years. Average follow-up was 25.7 months. There were
      eight partial-thickness, 26 small, 40 medium, 39 large and 15 massive tears.
      After arthroscopic glenohumeral examination and subacromial decompression, we
      made a 3- to 4-cm skin incision from anterolateral edge of the acromion and
      dissected to the raphe between the anterior and middle deltoid. The torn tendon
      was repaired with single- or double-row technique using suture anchors. To
      prevent avulsion of the deltoid from the acromion, additional suturing within the
      bone tunnel was performed. We retrospectively evaluated clinical outcomes using
      the American Shoulder and Elbow Surgeon (ASES) scoring system. RESULTS: The
      average visual analogue scale (VAS), activity of daily living (ADL) and ASES
      scores improved, respectively, from 6.6, 12.0 and 36.7 preoperatively to 1.2,
      26.6 and 88.2 postoperatively. There were 71 excellent, 39 good, ten fair and
      eight poor results. There were no statistically significant difference between
      final ASES scores and age, symptom duration, tear size or preoperative stiffness,
      but men had significantly higher final ASES scores than women (P = 0.014).
      CONCLUSION: Anterolateral approach for mini-open rotator cuff repair produces
      satisfactory results. It may also provide better visualisation for rotator cuff
      tears of all sizes.

PMID- 21717202
TI  - Metal speciation studies in the aquifer sediments of Semria Ojhapatti, Bhojpur
      District, Bihar.
AB  - The pollution of aquifer sediments by heavy metals has assumed serious concern
      due to their toxicity and accumulative behavior. Changes in environmental
      conditions can strongly influence the behavior of both essential and toxic
      elements by altering the forms in which they occur and therefore quantification
      of the different forms of metal is more meaningful than total metal
      concentrations. In this study, fractionation of metal ions in aquifer sediments
      of Semria Ojhapatti area, Bhojpur district, Bihar has been studied to determine
      the ecotoxic potential of metal ions. The investigations suggest that iron,
      copper, and arsenic have a tendency to remain associated in the following order
      residual > reducible > acid-soluble > oxidizable; manganese and zinc have
      tendency to be associated as residual > acid-soluble > reducible > oxidizable.
      The risk assessment code reveals that manganese and zinc occur in significant
      concentration in acid-soluble fraction and therefore comes under the high risk
      category and can easily enter the food chain. Most of the iron, copper, and
      arsenic occur as immobile fraction (i.e. residual) followed by its presence in
      reducible fraction and would pose threat to the water quality due to changing
      redox conditions. The metal enrichment factor in the study area shows moderate to
      significant metal enrichment in the aquifer sediments which may pose a real
      threat in near future. The geo-accumulation index of metals also shows that the
      metals lie in the range of strongly contaminated (for iron at shallow depths) to
      moderately contaminated to uncontaminated values.

PMID- 21717203
TI  - Nitrate, sulphate and chloride contents in public drinking water supplies in
      Sicily, Italy.
AB  - Water samples collected from public drinking water supplies in Sicily were
      analysed for electric conductivity and for their chloride, sulphate and nitrate
      contents. The samples were collected as uniformly as possible from throughout the
      Sicilian territory, with an average sampling density of about one sample for
      every 7,600 inhabitants. Chloride contents that ranged from 5.53 to 1,302 mg/l
      were correlated strongly with electric conductivity, a parameter used as a proxy
      for water salinity. The highest values are attributable to seawater contamination
      along the coasts of the island. High chloride and sulphate values attributable to
      evaporitic rock dissolution were found in the central part of Sicily. The nitrate
      concentrations ranged from 0.05 to 296 mg/l, with 31 samples (4.7% of the total)
      exceeding the maximum admissible concentration of 50 mg/l. Anomalous samples
      always came from areas of intensive agricultural usage, indicating a clear
      anthropogenic origin. The same parameters were also measured in bottled water
      sold in Sicily, and they all were within the ranges for public drinking water
      supplies. The calculated mean nitrate intake from consuming public water supplies
      (16.1 mg/l) did not differ significantly from that of bottled water (15.2 mg/l).
      Although the quality of public water supplies needs to be improved by eliminating
      those that do not comply with the current drinking water limits, at present it
      does not justify the high consumption of bottled water (at least for nitrate
      contents).

PMID- 21717204
TI  - Origin of diderm (Gram-negative) bacteria: antibiotic selection pressure rather
      than endosymbiosis likely led to the evolution of bacterial cells with two
      membranes.
AB  - The prokaryotic organisms can be divided into two main groups depending upon
      whether their cell envelopes contain one membrane (monoderms) or two membranes
      (diderms). It is important to understand how these and other variations that are
      observed in the cell envelopes of prokaryotic organisms have originated. In 2009,
      James Lake proposed that cells with two membranes (primarily Gram-negative
      bacteria) originated from an ancient endosymbiotic event involving an
      Actinobacteria and a Clostridia (Lake 2009). However, this Perspective argues
      that this proposal is based on a number of incorrect assumptions and the data
      presented in support of this model are also of questionable nature. Thus, there
      is no reliable evidence to support the endosymbiotic origin of double membrane
      bacteria. In contrast, many observations suggest that antibiotic selection
      pressure was an important selective force in prokaryotic evolution and that it
      likely played a central role in the evolution of diderm (Gram-negative) bacteria.
      Some bacterial phyla, such as Deinococcus-Thermus, which lack lipopolysaccharide
      (LPS) and yet contain some characteristics of the diderm bacteria, are postulated
      as evolutionary intermediates (simple diderms) in the transition between the
      monoderm bacterial taxa and the bacterial groups that have the archetypal LPS
      containing outer cell membrane found in Gram-negative bacteria. It is possible to
      distinguish the two stages in the evolution of diderm-LPS cells (viz. monoderm
      bacteria -> simple diderms lacking LPS -> LPS containing archetypal diderm
      bacteria) by means of conserved inserts in the Hsp70 and Hsp60 proteins. The
      insert in the Hsp60 protein also distinguishes the traditional Gram-negative
      diderm bacterial phyla from atypical taxa of diderm bacteria (viz. Negativicutes,
      Fusobacteria, Synergistetes and Elusimicrobia). The Gram-negative bacterial phyla
      with an LPS-diderm cell envelope, as defined by the presence of the Hsp60 insert,
      are indicated to form a monophyletic clade and no loss of the outer membrane from
      any species from this group seems to have occurred. This argues against the
      origin of monoderm prokaryotes from diderm bacteria by loss of outer membrane.

PMID- 21717205
TI  - Geographical markers for Saccharomyces cerevisiae strains with similar
      technological origins domesticated for rice-based ethnic fermented beverages
      production in North East India.
AB  - Autochthonous strains of Saccharomyces cerevisiae from traditional starters used
      for the production of rice-based ethnic fermented beverage in North East India
      were examined for their genetic polymorphism using mitochondrial DNA-RFLP and
      electrophoretic karyotyping. Mitochondrial DNA-RFLP analysis of S. cerevisiae
      strains with similar technological origins from hamei starter of Manipur and
      marcha starter of Sikkim revealed widely separated clusters based on their
      geographical origin. Electrophoretic karyotyping showed high polymorphism amongst
      the hamei strains within similar mitochondrial DNA-RFLP cluster and one unique
      karyotype of marcha strain was widely distributed in the Sikkim-Himalayan region.
      We conceptualized the possibility of separate domestication events for hamei
      strains in Manipur (located in the Indo-Burma biodiversity hotspot) and marcha
      strains in Sikkim (located in Himalayan biodiversity hotspot), as a consequence
      of less homogeneity in the genomic structure between these two groups, their
      clear separation being based on geographical origin, but  not on technological
      origin and low strain level diversity within each group. The molecular markers
      developed based on HinfI-mtDNA-RFLP profile and the chromosomal doublets in
      chromosome VIII position of Sikkim-Himalayan strains could be effectively used as
      geographical markers for authenticating the above starter strains and
      differentiating them from other commercial strains.

PMID- 21717207
TI  - As time goes by?: the fallacy of thrombolysis in STEMI networks.
AB  - Primary percutaneous coronary intervention (PPCI) is superior to thrombolysis
      (TL) as reperfusion therapy in ST-elevation myocardial infarction (STEMI). TL is
      a rapidly available, but semi-effective therapy (effective reperfusion in 50% of
      patients only), whereas PPCI is a potentially delayed, but highly effective
      therapy (effective reperfusion in >90%). Since TL loses its efficacy beyond 2-3 h
      after symptom onset, it is a significant reperfusion alternative to PPCI in early
      presenters only. The individual decision to treat an early presenter with PPCI or
      TL requires the evaluation of the time delay between potential start of TL or
      PPCI, the PCI-related delay (PRD). PRD is greatest, if TL is given in the
      prehospital setting. Until now, prehospital TL as the most rapidly available
      reperfusion strategy has failed to demonstrate any prognostic or even any other
      relevant benefit compared to PPCI in any subgroup of patients, even with time
      delays for PPCI of up to several hours. On average, a median PRD of at least 90
      120 min can be considered a time corridor of prognostic superiority of PPCI over
      TL. This is already achieved in contemporary registries and myocardial infarction
      networks.Therefore, the efforts should not focus on the implementation of a dual
      reperfusion strategy (PPCI, and prehospital TL in selected cases) in established
      or upcoming myocardial infarction networks, but concentrate on the availability
      of PPCI in less than 2 h. TL, as rapid as possible, i.e. prehospital, is a vital
      treatment option in case of non-existing PPCI facilities within a median time
      limit of 2 h or even more, a scenario not existing or easily to eliminate in
      European countries by implementing well organized myocardial infarction networks.
      This is the mission to be accomplished.

PMID- 21717208
TI  - Parents' perceptions of water safety and quality.
AB  - Every day parents make choices about the source of water their families consume.
      There are many contributing factors which could affect decisions about water
      consumption including taste, smell, color, safety, cost, and convenience.
      However, few studies have investigated what parents with young children think
      about water quality and safety in the US and how this affects the choices they
      are making. This study aimed to describe the perceptions of parents with regard
      to water quality and safety and to compare bottled water and tap water use, as
      well as to examine motivation for water choices. We conducted an online
      questionnaire to survey parents living in Pennsylvania about water quality and
      safety, and preference for bottled versus tap water. Parents were recruited
      through child care centers, and 143 surveys were returned. The survey results
      showed high overall scores for perception of tap water quality and safety, and a
      preference for tap water over bottled water. We found that parents were concerned
      for the environmental impact that buying bottled water may have but were also
      concerned about potential contamination of tap water by natural gas drilling
      processes and nuclear power plants. These findings regarding parental concerns
      are critical to inform pediatric health care providers, water sellers, and
      suppliers in order that they may provide parents with the necessary information
      to make educated choices for their families.

PMID- 21717206
TI  - Diversity and abundance of ammonia-oxidizing prokaryotes in sediments from the
      coastal Pearl River estuary to the South China Sea.
AB  - In the present study the diversity and abundance of nitrifying microbes including
      ammonia-oxidizing archaea (AOA) and betaproteobacteria (beta-AOB) were
      investigated, along with the physicochemical parameters potentially affecting
      them, in a transect of surface sediments from the coastal margin adjacent to the
      Pearl River estuary to the slope in the deep South China Sea. Nitrifying
      microbial diversity was determined by detecting the amoA (ammonia monooxygenase
      subunit A) gene. An obvious community structure shift for both AOA and beta-AOB
      from the coastal marginal areas to the slope in the deep-sea was detected, while
      the OTU numbers of AOA amoA were more stable than those of the beta-AOB. The OTUs
      of beta-AOB increased with the distance from the coastal margin areas to the
      slope in the deep-sea. Beta-AOB showed lower diversity with dominant strains in a
      polluted area but higher diversity without dominant strains in a clean area.
      Moreover, the diversity of beta-AOB was correlated with pH values, while no
      noticeable relationships were established between AOA and physicochemical
      parameters. Beta-AOB was more sensitive to transect environmental variability and
      might be a potential indicator for environmental changes. Additionally, the
      surface sediments surveyed in the South China Sea harboured diverse and distinct
      AOA and beta-AOB phylotypes different from other environments, suggesting the
      endemicity of some nitrifying prokaryotes in the South China Sea.

PMID- 21717209
TI  - Working for mom and dad: are teens more likely to get injured working in family
      owned businesses?
AB  - Recent controversy regarding the issue of children working in family-owned
      businesses has come to the forefront, pitting safety and health versus parent's
      right to teach their children the family trade. While studies have characterized
      injury among working teens, no studies have assessed work and injury among teens
      employed in family-owned businesses. This study is the first to examine teenagers
      working in family-owned businesses and to compare the experiences of teens
      working in family-businesses to the experiences of other working teens. A
      questionnaire was distributed to 8,085 teens in high schools throughout the five
      public health regions of Wisconsin. A total of 6, 810 teens responded (84%).
      Overall 2,858 high school teens aged 14-17 reported working (42%); of which 963
      (34%) worked in a family-business. Teens working in family-businesses were more
      likely to report that their injury was severe, affecting their activities for
      more than three days, compared with other working teens (33% vs. 21%, P = 0.05).
      The percentage of teens working in family-businesses that reported broken bones
      or crushed body parts was 17% compared to only 5% of other-working teens.
      Additionally, teens employed in family-businesses were more likely to file for
      workers' compensation (28% vs. 12%, P = 0.005). Teens working in family-owned
      businesses may be at a greater risk for more severe injury based on the jobs and
      tasks they are doing. Teens working in family-owned businesses were more likely
      to report engaging in dangerous tasks, including some that are illegal under the
      Hazardous Occupation Orders. More research is needed to assess the dynamics that
      exist for teens working in family-owned businesses.

PMID- 21717210
TI  - Knowledge of hepatitis B risk factors and prevention practices among individuals
      chronically infected with hepatitis B in San Francisco, California.
AB  - Asian/Pacific Islanders (A/PIs) in the United States are disproportionately
      affected by the hepatitis B virus (HBV), which can cause a lifelong liver
      infection that may result in cirrhosis, liver failure, liver cancer, or death.
      Although previous studies have measured knowledge of hepatitis B transmission and
      prevention practices in A/PI communities, we present results from the first
      population-based study of this type, which specifically focuses on A/PIs who are
      chronically infected with HBV. Through telephone interviews, we assessed the HBV
      risk factor knowledge and prevention practices of a population-based, random
      sample of persons with chronic HBV who were reported to the San Francisco
      Department of Public Health between October 2007 and July 2009. Among 829
      respondents, 67% were foreign born A/PIs of Chinese ethnicity who did not speak
      English as their primary language. Among all respondents, 75% were unable to
      identify how they acquired HBV, and 41% said that they do nothing to prevent
      transmission of HBV to their close contacts. Knowledge of HBV risk factors and
      recommended prevention practices was poor among A/PIs who are chronically
      infected with HBV and who may transmit the infection to others.

PMID- 21717211
TI  - [Restless legs syndrome and nocturnal leg pain : Differential diagnosis and
      treatment].
AB  - Pain in the legs belongs to the five most frequent regional pain symptoms.
      Restless legs syndrome (RLS) presents a particular differential diagnosis for
      pain in the legs, which is characterized by a nocturnal urge to move the legs
      often associated with painful sensations in the legs. It is one of the most
      common neurological disorders and probably the leading cause of nocturnal pain in
      the legs. In this overview, the diagnosis and therapy of RLS as well as aspects
      of pain therapy of the disorder are presented. In addition, the differential
      diagnoses for exclusion of other specific causes of nocturnal pain in the legs
      are discussed.

PMID- 21717212
TI  - Serum macrophage colony-stimulating factor (M-CSF) in patients with Hodgkin
      lymphoma.
AB  - Macrophage colony-stimulating factor (M-CSF) was recently implicated by in vitro
      studies as a survival and proliferation factor for Hodgkin/Reed-Sternberg cells.
      We evaluated pre-treatment serum M-CSF levels in 66 patients with histopathologic
      diagnosis of classical Hodgkin lymphoma (HL) and looked for possible correlations
      with baseline clinical characteristics. Significantly higher M-CSF serum
      concentrations were found in patients with bulky mediastinal mass, systemic
      symptoms, and elevated ESR but not LDH. There was no significant association
      between M-CSF level and sex, clinical stage, number of lymph node areas involved,
      and histopathological subtype of HL. We conclude that serum M-CSF levels are
      frequently elevated in HL patients and are significantly related to the presence
      of bulky mediastinal mass and systemic symptoms. These observations may indicate
      a pathogenetic role of M-CSF in Hodgkin lymphoma.

PMID- 21717213
TI  - Established non-union of an operatively managed trans-scaphoid perilunate
      fracture dislocation progressing to spontaneous union.
AB  - Perilunate dislocations and fracture dislocations represent uncommon and unusual
      injuries that are often missed at initial presentation and diagnosed late in up
      to 25% of cases. Prompt open reduction, carpal stabilisation and ligamentous
      repair is required to reduce the risk of complications. We report a case of an
      established scaphoid non-union in an operatively managed perilunate fracture
      dislocation that spontaneously united almost 2 years after the initial injury,
      just before a planned revision scaphoid fixation with bone grafting. This case
      highlights the importance of initial clinical assessment together with
      appropriate radiographs and follow-up of these injuries post-operatively,
      especially when complications such as non-union arise.

PMID- 21717214
TI  - Distal patellar tendon avulsion fracture in a football player with osteogenesis
      imperfecta.
AB  - Proximal patellar tendon ruptures have been described in adults with osteogenesis
      imperfecta, but distal avulsions from the tibial tubercle have not. This is the
      first case reporting a distal patellar tendon avulsion fracture in a football
      player with osteogenesis imperfecta and the technique of surgical repair.

PMID- 21717216
TI  - The anterolateral ligament of the human knee: an anatomic and histologic study.
AB  - PURPOSE: The functional anatomy of the knee is frequently studied but remains
      incompletely understood. Numerous authors have described a structure in the
      lateral knee connecting the lateral femoral condyle with the lateral meniscus and
      tibial plateau. The goal of this study is to define the incidence, anatomy, and
      histology of this structure, the anterolateral ligament. METHODS: The incidence
      of the ligament was determined in 30 consecutive patients undergoing total knee
      arthroplasty (TKA) for medial compartment osteoarthritis. The anatomy and
      histology were evaluated using 10 cadaveric knees. RESULTS: The anterolateral
      ligament was noted to be present in all 40 knees. In all cases, it was noted to
      take origin near or on the popliteus tendon insertion and insert into the lateral
      meniscus and tibial plateau 5 mm distal to the articular surface and posterior to
      Gerdy's Tubercle. The average width of the relatively flat structure was 8.2 +/-
      1.5 mm, and the average length was 34.1 +/- 3.4 mm. Histologic analysis revealed
      a discreet structure with a fibrous core surrounded by synovium. Fibers blended
      with the popliteus at its origin and with the lateral meniscus as it passed
      distally. CONCLUSIONS: The anterolateral ligament may play a role in preventing
      anterior tibial translation. The role, if any, of this structure in meniscal
      stability and the pathology of meniscal tears remain unclear. LEVEL OF EVIDENCE:
      Not applicable-Descriptive Anatomic Study.

PMID- 21717217
TI  - Comparison of two minimally invasive implantation instrument-sets for total knee
      arthroplasty.

PMID- 21717218
TI  - Deletion of chromosome 4q predicts outcome in stage II colon cancer patients.
AB  - BACKGROUND: Around 30% of all stage II colon cancer patients will relapse and die
      of their disease. At present no objective parameters to identify high-risk stage
      II colon cancer patients, who will benefit from adjuvant chemotherapy, have been
      established. With traditional histopathological features definition of high-risk
      stage II colon cancer patients is inaccurate. Therefore more objective and robust
      markers for prediction of relapse are needed. DNA copy number aberrations have
      proven to be robust prognostic markers, but have not yet been investigated for
      this specific group of patients. The aim of the present study was to identify
      chromosomal aberrations that can predict relapse of tumor in patients with stage
      II colon cancer. MATERIALS AND METHODS: DNA was isolated from 40 formaldehyde
      fixed paraffin embedded stage II colon cancer samples with extensive
      clinicopathological data. Samples were hybridized using Comparative Genomic
      Hybridization (CGH) arrays to determine DNA copy number changes and
      microsatellite stability was determined by PCR. To analyze differences between
      stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank
      sum test was implemented with multiple testing correction. RESULTS: Stage II
      colon cancers of patients who had relapse of disease showed significantly more
      losses on chromosomes 4, 5, 15q, 17q and 18q. In the microsatellite stable (MSS)
      subgroup (n = 28), only loss of chromosome 4q22.1-4q35.2 was significantly
      associated with disease relapse (P < 0.05, FDR < 0.15). No differences in
      clinicopathological characteristics between patients with and without relapse
      were observed. CONCLUSION: In the present series of MSS stage II colon cancer
      patients losses on 4q22.1-4q35.2 were associated with worse outcome and these
      genomic alterations may aid in selecting patients for adjuvant therapy.

PMID- 21717219
TI  - Correlation of trace elemental profiles in blood samples of Indian patients with
      leukoplakia and oral submucous fibrosis.
AB  - In order to ascertain possible correlation between alterations in trace elemental
      profile and the progression or regression of two most common potentially
      malignant disorders affecting oral cavity, namely oral submucous fibrosis and
      leukoplakia, blood from 60 patients from each group of patients as well from 30
      healthy individuals was analyzed for elemental profiling employing EDXRF
      technique. Out of the 16 detected elements (K, Si, Ca, V, Cr, Ni, Mn, Fe, Cu, Zn,
      Se, Br, Rb, Sr, Co, and Pb), Mn, Fe, Zn, Br, and Co showed remarkable alteration
      in their profile in both leukoplakia and oral submucous fibrosis patients with
      respect to the normal healthy individuals. While Zn, Br, and Fe reflected similar
      changes--showing gross depletion in both the diseased groups, Mn and Co depicted
      inverse pattern of alterations in their concentrations in the two types of
      precancerous disorders when compared to the control subjects.

PMID- 21717220
TI  - Dream features in the early stages of Parkinson's disease.
AB  - Few studies have investigated the relation between dream features and cognition
      in Parkinson's disease (PD), although vivid dreams, hallucinations and cognitive
      decline have been proposed as successive steps of a pathological continuum. Our
      objectives were therefore to characterize the dreams of early stage PD and to
      study the relation between dream characteristics, cognitive function, motor
      status, depression, dopaminergic treatment, and the presence of REM sleep
      behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21
      matched control subjects were classified according to Hall and van de Castle
      system. h statistics was used to compare the dream content between patients and
      controls. We tested the relation between patients' dreams characteristics and
      cognitive function (Frontal assessment battery (FAB) and Mini-Mental State
      Examination tests) depression (Beck depression inventory), motor function
      (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical
      criteria) and hallucinations, using general linear model statistics. Patients and
      controls differed only on FAB scores. Relevant differences in the Hall and van de
      Castle scale were found between patient's dreams and those of the control group,
      regarding animals, aggression/friendliness, physical aggression, befriender
      (higher in the patient group) and aggressor and bodily misfortunes (lower in the
      patient group) features. Cognitive and particularly frontal dysfunction had a
      significant influence on the frequency of physical aggression and animal related
      features, while dopaminergic doses, depressive symptoms, hallucinations and RBD
      did not. We found a pattern of dream alteration characterized by heightened
      aggressiveness and the presence of animals. These were related to more severe
      frontal dysfunction, which could be the origin of such changes.

PMID- 21717221
TI  - Responding empathically: a question of heart, not a question of skin.
AB  - Empathy entails the capacities to resonate with another person's emotions,
      understand his/her thoughts and feelings, separate our own thoughts and emotions
      from those of the observed and responding with the appropriate prosocial and
      helpful behavior. While there is abundant research on the neurobiological
      mechanisms of some components of empathy (e.g., emotional contagion), few studies
      have considered the neurobiological mechanisms underlying the empathic response.
      The present study explores psychophysiological correlates (skin conductance level
      and the interbeat interval) as a function of the empathic response while
      participants watch and respond to actors portraying emotionally laden vignettes.
      Forty undergraduate psychology students were each presented with 40 emotional
      vignettes of positive or negative valence and asked to choose among three
      different empathic responses while their electrodermal and cardiac responses were
      measured. Overall, the study shows that higher levels of additive empathy are
      associated with increased cardiac activity (i.e., decreased Interbeat Interval)
      but not electrodermal activity.

PMID- 21717222
TI  - Quantitative trait loci in a bacterially induced model of inflammatory bowel
      disease.
AB  - Inflammatory bowel diseases (IBDs) are complex disorders caused by a combination
      of environmental, microbial, and genetic factors. Genome-wide association studies
      in humans have successfully identified multiple genes and loci associated with
      disease susceptibility, but the mechanisms by which these loci interact with each
      other and/or with environmental factors (i.e., intestinal microbiota) to cause
      disease are poorly understood. Helicobacter hepaticus-induced intestinal
      inflammation in mice is an ideal model system for elucidating the genetic basis
      of IBD susceptibility in a bacterially induced system, as there are significant
      differences in H. hepaticus-induced disease susceptibility among inbred mouse
      strains. Infected A/J mice develop acute overexpression of proinflammatory
      cytokines followed 2-3 months later by chronic cecal inflammation, whereas
      infected C57BL/6 mice fail to develop cecal inflammation or increased cytokine
      expression. The goal of this project was to use quantitative trait locus (QTL)
      mapping to evaluate genetic factors that contribute to the differential disease
      susceptibility between these two mouse strains. Using acute cecal IL-12/23p40
      expression as a biomarker for disease susceptibility, QTL analysis of H.
      hepaticus-infected F(2) mice revealed involvement of multiple loci. The loci with
      the strongest association were located on Chromosome 3 and Chromosome 17, with
      logarithm of odds (LOD) scores of 6.89 and 3.09, respectively. Cecal expression
      of IL-12/23p40 in H. hepaticus-infected C57BL/6J-Chr3(A/J)/NaJ chromosome
      substitution mice had an intermediate phenotype, significantly higher than in
      resistant C57BL/6 but lower than in susceptible A/J mice, confirming the
      importance of this locus to the immune response to H. hepaticus infection.

PMID- 21717223
TI  - Transcriptional variations mediated by an alternative promoter of the FPR3 gene.
AB  - Formyl peptide receptor 3 (FPR3) is a potential player in innate immunity and
      appears with FPR2 as a FPR cluster during primate evolution. Comparative genome
      analyses indicate that a segmental duplication (SD) event upstream of the FPR3
      gene after the divergence of New and Old World monkeys led to the emergence of an
      alternative promoter. In this study we combined computational and experimental
      approaches to identify a FPR3 gene that is controlled by an alternative promoter
      derived during a SD event. Its transcriptional activity was detected by
      quantitative reverse transcription polymerase chain reaction. Human alternative
      transcripts (FPR3-1 and FPR3-2) showed tissue-specific patterns with strong
      expressions in lung or uterus, while the FPR3-1 transcript of rhesus macaque is
      broadly expressed in various tissues. Overall, transcriptional variations of FPR3
      occur by an alternative promoter during primate evolution.

PMID- 21717224
TI  - Tissue inhibitor of metalloproteinases (TIMPs) in heart failure.
AB  - Remodeling of the myocardium and the extracellular matrix (ECM) occurs in heart
      failure irrespective of its initial cause. The ECM serves as a scaffold to
      provide structural support as well as housing a number of cytokines and growth
      factors. Hence, disruption of the ECM will result in structural instability as
      well as activation of a number of signaling pathways that could lead to fibrosis,
      hypertrophy, and apoptosis. The ECM is a dynamic entity that undergoes constant
      turnover, and the integrity of its network structure is maintained by a balance
      in the function of matrix metalloproteinases (MMPs) and their inhibitors, the
      tissue inhibitor of metalloproteinases (TIMPs). In heart disease, levels of MMPs
      and TIMPs are altered resulting in an imbalance between these two families of
      proteins. In this review, we will discuss the structure, function, and regulation
      of TIMPs, their MMP-independent functions, and their role in heart failure. We
      will review the knowledge that we have gained from clinical studies and animal
      models on the contribution of TIMPs in the development and progression of heart
      disease. We will further discuss how ECM molecules and regulatory genes can be
      used as biomarkers of disease in heart failure patients.

PMID- 21717225
TI  - [Use of nanoparticles in ophthalomology].
AB  - Nanotechnology, the manufacture and use of structures and implements of around a
      few 100 nm in size, is becoming a key technology of the twenty-first century. An
      important element for the manufacture of nanoparticles is gold. Gold
      nanoparticles can be custom made and chemically modified in their size and form.
      Initial investigations have shown that they are physiologically non-hazardous. A
      potential application is in neovascular age-related macular degeneration. Gold
      nanoparticles of suitable dimensions introduced into newly forming blood vessels
      can be targeted and heated which selectively destroys these blood vessels. This
      principle has already been demonstrated in cultivated endothelial cells.

PMID- 21717226
TI  - [Recommendations for a standardized perimetry within the framework of epilepsy
      surgery].
AB  - Epilepsy surgery aims to achieve a seizure-free outcome and to gain relevant
      socio-medicinal prospects for the patients. After successful temporal lobe
      resection eligibility for driving is established during the seizure-free period.
      However, extended postoperative homonymous visual field defects can preclude from
      driving. This article will give an overview of the objectives of postoperative
      perimetry, particularly with respect to the visual field criteria for driving and
      neurosurgical outcome evaluation. A literature review details the perimetry
      methods applied in neurosurgical outcome studies. Based on a discussion of
      methodological difficulties of visual field testing, suggestions for a uniform
      procedure for perimetric examinations are developed. Only a strict
      standardization with special consideration of the postoperative interval,
      examination strategies and quantification of the area of field lost allows
      meaningful comparisons between operation techniques, surgical approaches, target
      areas and surgical centres.

PMID- 21717227
TI  - [Loss of visual acuity after treatment with pipamperone].
AB  - The butyrophenone derivative pipamperone is a neuroleptic agent administered to
      reduce psychomotor agitation and psychotic conditions in schizophrenic psychoses.
      Among other things it blocks D2 receptors in the dopamine pathways of the
      mesolimbic system and therefore reduces excess release of dopamine in the area
      thought to control psychotic experiences. Dopamine also takes part in signal
      transduction in the visual process. Loss of visual acuity, color vision, scotoma
      and electrophysiological alterations were observed under treatment with different
      groups of neuroleptics which interfere with dopamine metabolism but have not yet
      been observed after therapy with pipamperone. We present the case of a young
      women suffering from unilateral loss of visual acuity after treatment with
      pipamperone.

PMID- 21717228
TI  - Monitoring oxygenation.
AB  - Cyanosis was used for a century after dentists began pulling teeth under 100%
      N(2)O in 1844 because brief (2 min) severe hypoxia is harmless. Deaths came with
      curare and potent anesthetic respiratory arrest. Leland Clark's invention of a
      polarographic blood oxygen tension electrode (1954) was introduced for
      transcutaneous PO2 monitoring to adjust PEEP and CPAP PO2 to prevent premature
      infant blindness from excess O2 (1972). Oximetry for warning military aviators
      was tried after WW II but not used for routine monitoring until Takuo Aoyagi
      (1973) discovered an equation to measure SaO2 by the ratio of ratios of red and
      IR light transmitted through tissue as it changed with arterial pulses. Pulse
      oximetry (1982) depended on simultaneous technology improvements of light
      emitting red and IR diodes, tiny cheap solid state sensors and micro-chip
      computers. Continuous monitoring of airway anesthetic concentration and oxygen
      also became very common after 1980. Death from anesthesia fell 10 fold between
      1985 and 2000 as pulse oximetry became universally used, but no proof of a
      causative relationship to pulse oximetry exists. It is now assumed that all
      anesthesiologist became much more aware of the dangers of prolonged hypoxia,
      perhaps by using the pulse oximeters.

PMID- 21717229
TI  - Gait pattern in inherited cerebellar ataxias.
AB  - Our aim was to perform a comprehensive analysis of the global and segmental
      features of gait in patients with genetically confirmed inherited ataxias.
      Sixteen patients with autosomal dominant (spinocerebellar ataxia, SCA1 or 2) or
      recessive (Friedreich's ataxia, FRDA) ataxia were studied. We used a motion
      analysis system to record gait kinematic and kinetic data. We measured the mean
      values of global (time-distance parameters, COM displacement, support moment) and
      segmental gait parameters (joint displacement and inter-joint coordination), as
      both discrete and continuous variables, and their variability and correlations
      with International Cooperative Ataxia Rating Scale (ICARS) scores. We found a
      marked difference in all global gait parameters between the ataxic patients and
      the controls and close correlations between longer stride and stance duration and
      lower gait, posture and total ICARS scores. The only difference between the two
      patient groups was a shorter step length in the FRDA patients. As regards the
      segmental features, we found a significantly different waveform shape for all
      continuous kinematic and kinetic measures between the ataxic patients and the
      healthy controls, but only minor differences for the discrete measures.
      Intersegmental coordination evaluated using the continuous relative phase method
      revealed an irregular alternating joint behaviour without clear evidence of the
      synchronous pattern of alternating proximal/distal joint seen in healthy
      subjects. For almost all gait parameters we observed a markedly higher intra
      subject variability in the ataxic patients versus the controls, which was
      strongly related to the clinical ICARS scores. Patients with chronic, progressive
      inherited ataxias lose the ability to "stabilize" a walking pattern that can be
      repeated over time. The most peculiar aspect of the gait of inherited ataxia
      patients, regardless the different genetic forms, seems to be the presence of
      increased variability of all global and segmental parameters rather than an
      invariant abnormal gait pattern.

PMID- 21717230
TI  - Contribution of the cerebellum to the coupling of grip force and pull force
      during an isometric precision grip task.
AB  - This study addresses the influence of the cerebellum on the performance of an
      isometric precision grip task. For the task, in which the process of "picking a
      raspberry" is simulated, grip force and pull force had to be increased linearly
      for a duration of 1-5 s (pull phase) to accomplish the task skillfully. The
      performance of 11 patients suffering from degenerative cerebellar disease was
      analyzed and compared with the performance of 11 age- and sex-matched healthy
      control subjects. Patients with cerebellar disease showed systematic deviations
      of the pull force slope from a linear trend, dividing the pull phase into two
      intervals. After an initial sharp and brief increase of pull force (first
      interval), patients maintained the achieved pull force level almost constant
      without further increase (second interval). Although controls showed changes in
      the pull force slope also, they increased pull force during the whole pull phase.
      Coupling of grip force and pull force was analyzed using stochastic frontier
      analysis. This technique allows covariation of grip force and the resulting pull
      force to be analyzed depending on the variation of the grip force. In the
      patients, grip force and pull force were coupled efficiently only in the first
      interval. During the second interval, grip force was often exaggerated compared
      with pull force. In conclusion, patients with cerebellar diseases have
      difficulties in producing smooth isometric movements and in coupling grip force
      and pull force efficiently.

PMID- 21717231
TI  - Quantitative calculation of human melatonin suppression induced by inappropriate
      light at night.
AB  - Melatonin (C13H16N2O2) has a wide range of functions in the body. When is
      inappropriately exposed to light at night, human circadian rhythm will be
      interfered and then melatonin secretion will become abnormal. For nearly three
      decades great progresses have been achieved in analytic action spectra and
      melatonin suppression by various light conditions. However, so far few articles
      focused on the quantitative calculation of melatonin suppression induced by
      light. In this article, an algorithm is established, in which all the
      contributions of rods, cones, and intrinsically photosensitive retinal ganglion
      cells are considered. Calculation results accords with the experimental data in
      references very well, which indicate the validity of this algorithm. This
      algorithm can also interpret the rule of melatonin suppression varying with light
      correlated color temperature very well.

PMID- 21717232
TI  - Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) are
      more susceptible to retinal ischemic injury in vivo.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroprotective
      peptide exerting protective effects in neuronal injuries. We have provided
      evidence that PACAP is neuroprotective in several models of retinal degeneration
      in vivo. Our previous studies showed that PACAP treatment ameliorated the
      damaging effects of chronic hypoperfusion modeled by permanent bilateral carotid
      artery occlusion. We have also demonstrated in earlier studies that treatment
      with PACAP antagonists further aggravates retinal lesions. It has been shown that
      PACAP deficient mice have larger infarct size in cerebral ischemia. The aim of
      this study was to compare the degree of retinal damage in wild type and PACAP
      deficient mice in ischemic retinal insult. Mice underwent 10 min of bilateral
      carotid artery occlusion followed by 2-week reperfusion period. Retinas were then
      processed for histological analysis. It was found that PACAP deficient mice had
      significantly greater retinal damage, as shown by the thickness of the whole
      retina, the morphometric analysis of the individual retinal layers, and the cell
      numbers in the inner nuclear and ganglion cell layers. Exogenous PACAP
      administration could partially protect against retinal degeneration in PACAP
      deficient mice. These results clearly show that endogenous PACAP reacts as a
      stress-response peptide that is necessary for endogenous protection against
      different retinal insults.

PMID- 21717233
TI  - Foamy urine and stiffened blood vessels.

PMID- 21717234
TI  - Acculturative stress, perceived discrimination, and vulnerability to suicide
      attempts among emerging adults.
AB  - Cultural factors are often neglected in studies of suicidal behavior among
      emerging adults. The present study examined acculturative stress and perceived
      discrimination as statistical predictors of a suicide attempt history among an
      ethnically diverse sample of 969 emerging adults, ages 18-25 (M = 18.8). Females
      made up 68% of the sample, and the racial/ethnic composition included Asian,
      Latino, Black, and White (US-born and non-US-born) individuals. There were no
      statistically significant racial/ethnic differences in endorsement of a suicide
      attempt history, with an overall rate of 8% in the sample. Asian participants
      reported higher acculturative stress than all other racial/ethnic groups, while
      both Asian and Black participants reported having experienced more discrimination
      in the previous year, compared to other groups. Logistic regression analyses
      suggested that familial acculturative stress was associated with 2 times higher
      odds of endorsing a past suicide attempt, overall. More specifically, it was
      associated with over 2 times higher odds among Asian participants, over 4 times
      higher odds among Black participants, and over 3 times higher odds among non-US
      born White participants, while social acculturative stress was associated with
      over 3 times higher odds of endorsing a past suicide attempt among Latino
      participants. Environmental acculturative stress was associated with decreased
      odds of endorsing a suicide attempt history, overall, but not when examined
      separately by racial/ethnic group. Perceived discrimination was associated with
      over 5 times higher odds of a suicide attempt, overall, and specifically was
      associated with over 3 times higher odds among Latino participants and over 10
      times higher odds among White, US-born participants. These findings suggest the
      importance of addressing culturally-related variables in treatment with emerging
      adults of racially/ethnically diverse backgrounds to reduce risk for suicidal
      behavior.

PMID- 21717235
TI  - A novel global search algorithm for nonlinear mixed-effects models using particle
      swarm optimization.
AB  - NONMEM is one of the most popular approaches to a population
      pharmacokinetics/pharmacodynamics (PK/PD) analysis in fitting nonlinear mixed
      effects models. As a local optimization algorithm, NONMEM usually requires an
      initial value close enough to the global optimum. This paper proposes a novel
      global search algorithm called P-NONMEM. It combines the global search strategy
      by particle swarm optimization (PSO) and the local estimation strategy of NONMEM.
      In the proposed algorithm, initial values (particles) are generated randomly by
      PSO, and NONMEM is implemented for each particle to find a local optimum for
      fixed effects and variance parameters. P-NONMEM guarantees the global
      optimization for fixed effects and variance parameters. Under certain regularity
      conditions, it also leads to global optimization for random effects. Because P
      NONMEM doesn't run PSO search for random effect estimation, it avoids tremendous
      computational burden. In the simulation studies, we have shown that P-NONMEM has
      much improved convergence performance than NONMEM. Even when the initial values
      were far away from the global optima, P-NONMEM converged nicely for all fixed
      effects, random effects, and variance components.

PMID- 21717236
TI  - A longitudinal analysis of the relationship between fertility timing and
      schooling.
AB  - This article quantifies the contribution of pre-treatment dynamic selection to
      the relationship between fertility timing and postsecondary attainment, after
      controlling for a rich set of predetermined characteristics. Eventual mothers and
      nonmothers are matched using their predicted birth hazard rate, which shares the
      desirable properties of a propensity score but in a multivalued treatment
      setting. I find that eventual mothers and matched nonmothers enter college at the
      same rate, but their educational paths diverge well before the former become
      pregnant. This pre-pregnancy divergence creates substantial differences in
      ultimate educational attainment that cannot possibly be due to the childbirth
      itself. Controls for predetermined characteristics and fixed effects do not
      address this form of dynamic selection bias. A dynamic model of the simultaneous
      childbirth-education sequencing decision is necessary to address it.

PMID- 21717237
TI  - Factors determining the success of radiofrequency denervation in lumbar facet
      joint pain: a prospective study.
AB  - BACKGROUND AND AIMS: Radiofrequency denervation (RF) of the lumbar facet joints
      has been shown to be effective in well-selected patients. However, long-term
      success varies between studies. We evaluated the influence of selected
      psychosocial and constitutional factors on the outcome of RF, expressed as the
      duration of pain relief. METHODS: This prospective observational study included
      44 patients who received RF denervations at the University Hospital of Berne.
      Success was defined as at least 50% pain reduction 7-21 days, 6 months and 1 year
      after RF therapy. The Cox-regression analysis was performed to evaluate the
      influence of the following factors on the duration of success: age, sex,
      depression, work inability and previous surgery. RESULTS: Complete follow-up was
      available for 41 patients. The success rate 7-21 days after the denervation was
      76%. It decreased to 32% at 6 months and to 22% at 1 year. The median success
      duration was 17 weeks (95% CI 10-26). The Cox-regression analysis showed a
      significant shorter duration of success for patients with depression (hazard
      ratio [HR] 2.97, 95% CI 1.32-6.65), previous surgery (HR 2.39, 95% CI 1.10-5.21)
      and number of treated joints (HR 1.95 for each increase in the number of joints,
      95% CI 1.14-3.33). In bivariate analyses, only depression was kept to be
      significant. CONCLUSIONS: Depression seems to be related with a short duration of
      success. Based on these findings, a comprehensive study is warranted to evaluate
      whether psychosocial factors have to be considered when recruiting patients for
      radiofrequency denervation.

PMID- 21717238
TI  - Vertebral artery injuries following cervical spine trauma: a prospective
      observational study.
AB  - PURPOSE: The purpose of this study was to report on the incidence, diagnosis and
      clinical manifestation of VAI following cervical spine injuries observed in a
      prospective observational study with a standardized clinical and radiographical
      protocol. METHODS: During a 16-year period, 69 (mean age: 43 +/- 20.7 years; 25
      female, 44 male) of 599 patients had cervical spine injury suspicious for VAI due
      to facet luxation and/or fractures extending into the transverse foramen.
      Diagnosis and management of these patients followed a previously published
      protocol (Kral in Zentralbl Neurochir 63:153-158, 2002). Digital subtraction
      angiography (DSA) was performed in all 69 patients. Injury grading of VAI was
      done according to Biffl et al. (Ann Surg 231:672-681, 2000). All patients with
      VAI were treated with anticoagulation (heparin followed by ASS) for 6 months.
      RESULTS: In cases suspicious for VAI, the incidence of VAI detected by DSA was
      27.5% (n = 19 of 69 patients). VAI Grade I occurred in 15.8%, Grade II in 26.3%,
      Grade IV in 52.6% and Grade V in 5.2%. Of 19 patients, 4 (21%) had clinical signs
      of vertebrobasilar ischemia. Two patients died in hospital after 4 and 21 days
      respectively. Of 69 patients, 33 (47.8%) with suspected VAI had unstable spine
      injuries and were treated surgically. CONCLUSION: In patients with cervical spine
      fractures or dislocations crossing the course of the vertebral artery, VAI are
      relatively frequent and may be associated with significant morbidity and
      mortality. VAI were identified by DSA in 27.5%. Despite anticoagulation therapy,
      5.8% became clinically symptomatic and 2.9% died due to cerebrovascular ischemia.

PMID- 21717239
TI  - Liver resection of colorectal liver metastases in elderly patients.
AB  - BACKGROUND: The percentage of elderly patients with colorectal liver metastases
      (CLM) has increased. Liver resection remains the only curative therapy; data
      evaluating the outcome in this age group is limited. Aim of the present study was
      to determine if postoperative morbidity, mortality, and other independent
      predictors influence survival in patients >= 70 years undergoing liver resection
      for CLM. METHODS: Clinical data on primary tumor and metastases of 939 patients
      after liver resection for CLM between 1994 and 2008 were retrospectively
      collected and subdivided in three age-groups (>= 70, 40-69, <40). Independent
      predictors of survival were evaluated with overall and age-specific univariate
      and multivariate Cox regression models. RESULTS: A total of 939 patients
      underwent liver resection for CLM, 20.3% aged >= 70 years. Overall postoperative
      mortality and morbidity were 1.08 and 14.82%, revealing no age-related
      differences. With 5-year survival of 31.8% in the elderly and 37.5% in the mid
      age population, age >= 70 years was linked with decreased survival (Hazard Ratio
      [HR] = 1.305; P = 0.0186). Multivariate overall analyses showed size of CLM > 50
      mm (HR = 1.376; P = 0.0060), a high amount of transfusion during surgery (HR =
      1.676; P = 0.0110), duration of surgery >210 min (HR = 1.241; P = 0.0322),
      primary UICC (International Union Against Cancer) stage IV (HR = 2.297; P <
      0.0001), and performance of repeat resections (HR = 0.652; P = 0.0107) as
      independent predictors of survival. In the elderly group, effects of UICC IV (HR
      = 3.260; P = 0.0148) and high numbers of transfusions (HR = 3.647; P = 0.0129)
      were confirmed; the others did not show statistical significance. CONCLUSIONS:
      Resection of CLM at older age is feasible with morbidity and mortality rates
      similar to those in younger patients. Although age >= 70 was shown to be
      associated with poorer overall outcome, reasonable 5-year survival was observed.

PMID- 21717240
TI  - Assessment of the nodal status in ampullary carcinoma: the number of positive
      lymph nodes versus the lymph node ratio.
AB  - BACKGROUND: This study was intended to compare the prognostic power of the number
      of positive lymph nodes with that of the lymph node ratio in patients with
      ampullary carcinoma. METHODS: A retrospective analysis was conducted of the
      medical records of 71 consecutive patients with ampullary carcinoma who underwent
      pancreaticoduodenectomy with regional lymph node dissection. A total of 2151
      lymph nodes were dissected (median: 28 nodes per patient) and examined
      histologically. Cutoff points were determined for both the number of positive
      nodes and the lymph node ratio using chi(2) scores calculated with the Cox
      proportional hazards regression model. RESULTS: Lymph node metastasis was found
      in 34 patients. The best cutoff point for the number of positive nodes was
      identified as three nodes, and that for the lymph node ratio was identified as
      10%. Univariate analysis revealed both the number of positive nodes (0, 1-3, or
      >= 4; P < 0.0001) and the lymph node ratio (0%, 0-10%, or >10%; P < 0.0001) as
      significant prognostic factors. Multivariate analysis identified the number of
      positive nodes as an independent prognostic factor (P < 0.001), whereas the lymph
      node ratio failed to remain as an independent variable. The cumulative 5-year
      survival rates were 85% for patients with 0 positive nodes, 63% for patients with
      1-3 positive nodes, and 0% for patients with >= 4 positive nodes (P < 0.0001).
      CONCLUSIONS: The number of positive lymph nodes better predicts the outcome after
      resection than the lymph node ratio in patients with ampullary carcinoma.

PMID- 21717241
TI  - Risk factors for stroke during surgery for carotid body tumors.
AB  - BACKGROUND: Removing carotid body tumors (CBTs) carry the risk of operative
      morbidity including stroke. We evaluated the risk factors for stroke related to
      resection of CBTs. METHODS: We retrospectively reviewed the records of 17
      procedures performed on 16 patients with CBT between March 1998 and September
      2008. RESULTS: The study population consisted of 5 men and 11 women, of mean age
      41.7 years (range: 23-62 years). At surgery, 8 cases (47%) were localized and
      classified as Shamblin class I, 4 cases (23.5%) as class II, and 5 cases (29.4%)
      as class III. Four patients had postoperative stroke (23.5%), with Shamblin
      classification related to the incidence of stroke (P = 0.041). In contrast,
      neither tumor size (P = 0.412) nor heparin injection before internal carotid
      artery (ICA) manipulation (P = 0.538) was associated with stroke. Although
      preoperative embolization of the tumor feeder did not significantly reduce the
      stroke rate (P = 0.579), early external carotid artery (ECA) division in patients
      with class II and III tumors was effective (P = 0.008). Internal carotid artery
      (ICA) manipulation, including reconstruction, ligation, and repair of injury,
      significantly increased the incidence of stroke (P = 0.029), as did ICA ligation
      without reconstruction (P = 0.044). CONCLUSIONS: Internal carotid artery
      manipulation, including reconstruction, ligation, and repair of injury,
      significantly increased the incidence of stroke. For uncomplicated CBT resection,
      careful preoperative planning, especially for patients with class II and III
      tumors, is mandatory to avoid inadvertent ICA manipulation necessitated by
      bleeding. Early ECA division during the operation rather than preoperative
      percutaneous embolization in patients with class II and III tumors was
      significantly effective in reducing the stroke rate.

PMID- 21717242
TI  - New approaches in thyroid surgery: is there an increased risk of nerve injury?

PMID- 21717243
TI  - Reduction/prevention of lower extremity lymphedema after pelvic and para-aortic
      lymphadenectomy for patients with gynecologic malignancies.
AB  - BACKGROUND: Lower extremity lymphedema (LEL) is a serious complication caused by
      lymphadenectomy in patients with gynecologic malignancies. In this study, we
      evaluated the effect of preserving the circumflex iliac lymph nodes (CILNs),
      i.e., the most caudal external iliac lymph nodes, for the prevention and
      reduction of LEL by comparing two groups of patients, one in which CILN were
      removed and the other in which CILNs were preserved. METHODS: We retrospectively
      reviewed 329 patients with gynecologic malignancies who had undergone abdominal
      complete systematic pelvic and para-aortic lymphadenectomy. The patients were
      divided into nonpreserved (n = 189) and preserved (n = 140) groups, depending on
      whether CILNs were removed. Primary outcome measures included the incidence and
      severity of LEL. RESULTS: The incidence of LEL was significantly lower in the
      preserved group than in the nonpreserved group (P < 0.0001). The frequency of LEL
      was also significantly lower in the preserved group than in the nonpreserved
      group regardless of the range of pelvic and para-aortic lymphadenectomy (P <
      0.0001). LEL in the overwhelming majority of cases in the preserved group was
      mild, and no patients experienced severe LEL. Further, the incidence of
      cellulitis was 0% in the preserved group, while it was 12.7% in the nonpreserved
      group (P < 0.0001). Lymphoscintigraphy revealed collateral pathways from the
      preserved CILN along the iliac and large abdominal vessels. CONCLUSIONS: This
      method of lymph node preservation is a simple and extremely effective approach
      for preventing/reducing LEL after pelvic and para-aortic lymphadenectomy for
      patients with gynecologic malignancies.

PMID- 21717245
TI  - To cut is to cure: can we really apply Z11 in practice?

PMID- 21717246
TI  - Overexpression of renal tumor antigen is associated with tumor invasion and poor
      prognosis of hepatocellular carcinoma.
AB  - PURPOSE: The aim of this study was to investigate the roles of renal tumor
      antigen (RAGE) in the progression and clinical outcome of hepatocellular
      carcinoma (HCC). METHODS: RAGE mRNA levels in 350 cases of HCC were investigated
      by quantitative real-time reverse transcription polymerase chain reaction. We
      analyzed the relationship of RAGE mRNA level with clinicopathologic parameters
      and clinical outcome. To identify the possible role of RAGE on cellular invasion,
      we performed in vitro analyses using small interfering RNAs (siRNAs). RESULTS:
      RAGE mRNA level was significantly higher in HCC than in noncancerous hepatic
      tissues (P < 0.001). Overexpression of RAGE was significantly correlated with the
      presence of multiple tumors (P = 0.021), high alfa-fetoprotein level (P = 0.042),
      and advanced tumor stage (P = 0.016). Higher levels of RAGE expression were
      associated with significantly shorter overall survival time (P = 0.029).
      Knockdown of RAGE expression by siRNAs suppressed the invasive ability of HCC
      cells and the expression and secretion of matrix metalloproteinase-9 (MMP-9). We
      found that RAGE and MMP-9 expressions were correlated in HCCs, and furthermore,
      the combination of RAGE and MMP-9 expression was associated with the survival of
      patients (P = 0.0066). CONCLUSIONS: Our results suggest that RAGE may be
      important in tumor invasion and could be a potential predictor for the prognosis
      of HCC patients.

PMID- 21717247
TI  - The potential impact of the National Osteoporosis Foundation guidance on
      treatment eligibility in the USA: an update in NHANES 2005-2008.
AB  - This analysis of National Health and Nutrition Examination Survey (NHANES) 2005
      2008 data describes the prevalence of risk factors for osteoporosis and the
      proportions of men and postmenopausal women age 50 years and older who are
      candidates for treatment to lower fracture risk, according to the new Fracture
      Risk Assessment Tool (FRAX)-based National Osteoporosis Foundation Clinician's
      Guide. INTRODUCTION: It is important to update estimates of the proportions of
      the older US population considered eligible for pharmacologic treatment for
      osteoporosis for purposes of understanding the health care burden of this
      disease. METHODS: This is a cross-sectional study of the NHANES 2005-2008 data in
      3,608 men and women aged 50 years and older. Variables in the analysis included
      race/ethnicity, age, lumbar spine and femoral neck bone mineral density, risk
      factor profiles, and FRAX 10-year fracture probabilities. RESULTS: The prevalence
      of osteoporosis of the femoral neck ranged from 6.0% in non-Hispanic black to
      12.6% in Mexican American women. Spinal osteoporosis was more prevalent among
      Mexican American women (24.4%) than among either non-Hispanic blacks (5.3%) or
      non-Hispanic whites (10.9%). Treatment eligibility was similar in Mexican
      American and non-Hispanic white women (32.0% and 32.8%) and higher than it was in
      non-Hispanic black women (11.0%). Treatment eligibility among men was 21.1% in
      non-Hispanic whites, 12.6% in Mexican Americans, and 3.0% in non-Hispanic blacks.
      CONCLUSIONS: Nineteen percent of older men and 30% of older women in the USA are
      at sufficient risk for fracture to warrant consideration for pharmacotherapy.

PMID- 21717248
TI  - Acute thrombotic mesenteric ischemia: primary endovascular treatment in eight
      patients.
AB  - INTRODUCTION: The purpose of this study was to evaluate our experience with
      initial percutaneous transluminal angioplasty (PTA) +/- stenting as valuable
      options in the acute setting. METHODS: Between 2003 and 2008, eight patients with
      abdominal angio-MDCT-scan proven thrombotic AMI benefited from initial PTA +/-
      stenting. We retrospectively assessed clinical and radiological findings and
      their management. Seven patients presented thrombosis of the superior mesenteric
      artery, and in one patient both mesenteric arteries were occluded. All patients
      underwent initial PTA and stenting, except one who had balloon PTA alone. One
      patient was treated by additional in situ thrombolysis. RESULTS: Technical
      success was obtained in all patients. Three patients required subsequent surgery
      (37.5%), two of whom had severe radiological findings (pneumatosis intestinalis
      and/or portal venous gas). Two patients (25%) died: both had NIDD, an ASA score
      >=4, and severe radiologic findings. Satisfactory arterial patency was observed
      after a follow-up of 15 (range, 11-17) months in five patients who did not
      require subsequent surgery, four of whom had abdominal guarding but no severe CT
      scan findings. One patient had an ileocecal stenosis 60 days after the procedure.
      CONCLUSIONS: Initial PTA +/- stenting is a valuable alternative to surgery for
      patients with thrombotic AMI even for those with clinical peritoneal irritation
      signs and/or severe radiologic findings. Early surgery is indicated if clinical
      condition does not improve after PTA. The decision of a subsequent surgery must
      be lead by early clinical status reevaluation. In case of underlying
      atherosclerotic lesion, stenting should be performed after initial balloon
      dilatation.

PMID- 21717250
TI  - Reverse chimney or periscope: some issues have to be addressed "Re: Endovascular
      aneurysm repair using a reverse chimney technique in a patient with Marfan
      syndrome and contained ruptured chronic type B dissection".

PMID- 21717251
TI  - Long-term follow-up of uterine artery embolization for symptomatic adenomyosis.
AB  - INTRODUCTION: Long-term results of uterine artery embolization (UAE) for
      adenomyosis are largely unknown. We assess long-term outcome of UAE in 40 women
      with adenomyosis. MATERIALS AND METHODS: Between March 1999 and October 2006, 40
      consecutive women with adenomyosis (22 in combination with fibroids) were treated
      with UAE. Changes in junction zone thickness were assessed with magnetic
      resonance imaging (MRI) at baseline and again at 3 months. After a mean clinical
      follow-up of 65 months (median 58 [range 38-129]), women filled out the uterine
      fibroid symptom and quality of life (UFS-QoL) questionnaire, which had additional
      questions on the long-term evolution of baseline symptoms and adverse events.
      RESULTS: During follow-up, 7 of 40 women (18%) underwent hysterectomy. Among
      these 7 women, the junction zones were significantly thicker, both at baseline
      (mean 23 vs. 16 mm, P = 0.028) and at 3-month follow-up (mean 15 vs. 9 mm, P =
      0.034). Of 33 women with preserved uterus, 29 were asymptomatic. Four patients
      had symptom severity scores of 50 to 85 and overall QoL scores of 60 to 66,
      indicating substantial clinical symptoms. There was no relation between clinical
      outcome and the initial presence of fibroids in addition to adenomyosis.
      CONCLUSION: In women with therapy-resistant adenomyosis, UAE resulted in long
      term preservation of the uterus in the majority. Most patients with preserved
      uterus were asymptomatic. The only predictor for hysterectomy during follow-up
      was initial thickness of the junction zone. The presence or absence of fibroids
      in addition to adenomyosis had no relation with the need for hysterectomy or
      clinical outcome.

PMID- 21717252
TI  - Can a food justice movement improve nutrition and health? A case study of the
      emerging food movement in New York City.
AB  - In response to increasing obesity, diabetes, and food-related contributions to
      climate change, many individuals and organizations are mobilizing to advocate for
      healthier and more just local and national food policies and systems. In this
      report, we describe and analyze the food movement in New York City, examine
      tensions within it, and consider its potential role in improving health and
      nutrition. We conclude by suggesting that public health professionals can amplify
      the health effects of such movements by creating opportunities for dialog with
      movement participants, providing resources such as policy-relevant scientific
      evidence, documenting problems and evaluating policies, and offering technical,
      political, and organizational development expertise.

PMID- 21717253
TI  - Unsafe injection and sexual risk behavior among injecting drug users in Georgia.
AB  - Injection drug users (IDUs) are at risk for acquiring human immunodeficiency
      virus (HIV) through parenteral and sexual transmission. In this paper, we
      describe the prevalence and correlates of unsafe drug injecting and sexual
      behaviors among IDUs recruited across five cities in Georgia in 2009. IDUs were
      administered a questionnaire collecting information on demographics, drug use,
      sexual behaviors, and HIV testing behaviors. Correlates of risky injecting and
      sexual behaviors were determined using logistic regression. Of 1,127 IDUs, the
      majority (98.7%) were men, and the median duration of injecting drugs was 7
      years. Unsafe injecting behavior at last injection was reported by 51.9% of IDUs,
      while 16.8% reported both unsafe injecting behavior and not using condoms with
      last occasional and/or commercial partner. In the multivariate analysis,
      independent correlates of unsafe injecting behavior at last injection were types
      of drugs injected [p = 0.0096; (for ephedrine, adjusted odds ratio (aOR) = 7.38;
      95% CI, 1.50-36.26)] and not using condoms at last commercial sex (aOR = 2.29,
      1.22-4.32). The following variables were significantly associated with unsafe
      injecting behavior at last injection and not using condoms at last sex with
      commercial and/or occasional partners in the multivariate analysis: marital
      status [p = 0.0002; (for divorced, widowed, and separated aOR = 2.62, 1.62-4.25;
      for single aOR = 1.61, 1.08-2.39)], being a member of a regular injecting group
      (aOR = 0.62, 0.44-0.88), types of drugs injected in the past month [p = 0.0024;
      (for buprenorphine aOR = 0.34, 0.18-0.63)], city of residence (p = 0.0083), and
      not receiving information on HIV (aOR = 1.82, 1.07-3.09). Though only ephedrine
      was injected by a smaller number of IDUs (9.1%), the vast majority of these
      (81.4%) reported unsafe injecting practices at last injection. High prevalence of
      unsafe injecting behaviors and diverse and at-risk sexual partnerships highlight
      the need to implement complex and targeted HIV interventions among IDUs in
      Georgia.

PMID- 21717254
TI  - Theory of long distance interaction between antibodies and antigens.
AB  - Measuring the kinetics of antigen-antibody bindings we found an unexpected effect
      that can be explained by an automatic long distance detection of antigens by
      antibodies over up to 2 mm. We have developed a theory based on phase locking of
      THz waves, which leads antibodies automatically to their antigens. A mathematical
      proof of principle is done.

PMID- 21717255
TI  - Time-correlated single photon counting for simultaneous monitoring of zinc oxide
      nanoparticles and NAD(P)H in intact and barrier-disrupted volunteer skin.
AB  - PURPOSE: There is a lack of relevant, non-animal alternatives for assessing
      exposure and toxicity of nanoparticle-containing cosmetics, e.g. sunscreens. Our
      goal was to evaluate timecorrelated single photon counting (TCSPC) for
      simultaneous monitoring of zinc oxide nanoparticles (ZnO-NP) and the metabolic
      state of volunteer skin. METHODS: We separated the fluorescence lifetime
      signatures of endogenous fluorophore signals (i.e. nicotinamide adenine
      dinucleotide phosphate, NAD(P)H and keratin) and the ZnO-NP signal using advanced
      TCSPC to simultaneously determine ZnO-NP penetration profiles and NAD(P)H changes
      in subjects with altered barrier function, including tape-stripped skin and in
      psoriasis or atopic dermatitis lesions. RESULTS: We detected no ZnO-NP
      penetration into viable human skin in any group. ZnO-NP signal was significantly
      increased (p < 0.01) on the surface of tape-stripped and lesional skin after 4
      and 2 h of treatment, respectively. Free NAD(P)H signal significantly increased
      in tape-stripped viable epidermis treated for 4 h of ZnO-NP compared to vehicle
      control. No significant NAD(P)H changes were noted in the lesional study.
      CONCLUSION: TCSPC techniques enabled simultaneous, real-time quantification of
      ZnO-NP concentration and NAD(P)H via non-invasive imaging in the stratum corneum
      and viable epidermis of volunteers.

PMID- 21717256
TI  - Long-acting poly(DL:lactic acid-castor oil) 3:7-bupivacaine formulation: effect
      of hydrophobic additives.
AB  - PURPOSE: To reduce formulation viscosity of bupivacaine/poly(DL lactic acid co
      castor oil) 3:7 without increasing bupivacaine release rates. METHODS: Poly(DL
      lactic acid) 3:7 was synthesized and bupivacaine formulation prepared by mixing
      with additives ricinoleic acid or castor oil. In vitro release measurements
      identified optimum formulation. Anesthetized ICR mice were injected around left
      sciatic nerve using nerve stimulator with 0.1 mL of formulation. Animals received
      10% bupivacaine-polymer formulation with 10% castor oil (p(DLLA:CO)3:7-10% bupi
      10% CO) or 15% bupivacaine-polymer with 10% castor oil (p(DLLA:CO)3:7-15% bupi
      10% CO). Sensory and motor block were measured. RESULTS: Viscosity of 10% and 15%
      bupivacaine-p(DLLA:CO)3:7 formulations was reduced using hydrophobic additives;
      however, castor oil reduced bupivacaine release rates and eliminated burst
      effect. Less than 10% of the incorporated bupivacaine was released during 6 h,
      and less than 25% released in 24 h in vitro. In vivo formulation injection
      resulted in a 24 h motor block and a sensory block lasting at least 72 h.
      CONCLUSIONS: Incorporation of hydrophobic low-viscosity additive reduced
      viscosity in addition to burst release effects. Bupivacaine-polymer formulation
      with castor oil additive demonstrated prolonged sensory analgesia in vivo, with
      reduced duration of motor block.

PMID- 21717257
TI  - Use of the Goldman technique to correct both the overprojected and the broad
      nasal tip.
AB  - BACKGROUND: Tip surgery probably is the most challenging objective in modern
      rhinoplasty. The Goldman technique, despite its 50 years of history and its many
      variations proposed in the past, still remains a powerful tool for the surgeon
      who has to deal with an overprojected or broad nasal tip. METHODS: A
      retrospective review was performed for all the patients who underwent surgery
      with the Goldman technique by the senior author from 2004 to 2009 for correction
      of the broad or overprojected nasal tip. The clinical and pathologic findings of
      these patients were reviewed, and an independent observer evaluated the pre- and
      postoperative photos of the patients using five parameters: projection, rotation,
      symmetry, shape, and distance of the tip-defining points. The evaluation was
      performed using a scale of -1 to +1 for each of the five parameters. RESULTS: Of
      the 205 patients who underwent the technique, 115 (56%) were patients with
      overprojected tips, and 90 (44%) were patients with broad (boxy) tips. A total of
      189 cases (92.2%) involved primary rhinoplasties, and 16 cases (7.8%) involved
      revision. The mean follow-up period was 3 years (range, 1-5 years). During this
      period, complications were observed in five patients (2.4%), who underwent
      revision rhinoplasty with a successful result. The average score for the five
      parameters already mentioned for primary rhinoplasties according to the scale of 
      5 to +5 (resulting from the summation of all the parameters) showed a significant
      postoperative improvement (score, +4.3). The revision rhinoplasties showed
      significant improvement as well (score, +4.5). CONCLUSION: The Goldman technique
      is safe when performed by experienced surgeons and according to specific
      indications. This conclusion is indicated by the low rate of complications in the
      large series of patients in this study. When performed correctly, the Goldman
      technique provides a long-term aesthetic, functional, and natural result, which
      is the goal of modern functional rhinoplasty.

PMID- 21717258
TI  - Tissue degeneration 7 years after breast augmentation with injected
      polyacrylamide hydrogel (PAAG).
AB  - Injectable polyacrylamide hydrogel (PAAG) is a jelly-like transparent implant
      used in breast augmentations. This type of implant had been used since 1998, but
      its use was prohibited in China in 2006 due to numerous complications that had
      arisen from its use. In one case, a rare appearance of PAAG tissue degeneration
      was observed 7 years after an injectable breast augmentation using PAAG.

PMID- 21717259
TI  - Implant infection after augmentation mammaplasty: a review of the literature and
      report of a multidrug-resistant Candida albicans infection.
AB  - BACKGROUND: Implant breast augmentation is one of the most frequently performed
      surgical procedures, and fungal infection still is considered exceptional. This
      report presents a case of bilateral breast implant infection by multidrug
      resistant Candida albicans treated with a targeted antifungal therapy. METHODS: A
      young woman presented with breast pain and asymmetry as well as implant
      superficialization in the left breast 3 years after bilateral tuberous breast
      correction with implant insertion. She did not report any trauma to the chest
      wall or recent systemic infections. The breast was evaluated through mammary
      compliance analysis and magnetic resonance imaging (MRI). RESULTS: At surgery,
      both implants showed capsule contracture and were surrounded by a gelatinous
      yellow-brown and turbid fluid, which was sent for microbial and fungal analysis.
      A bilateral capsulectomy was performed. After copious irrigation of the
      subglandular pockets, submuscular pockets were created, and implants were
      substituted. Culture swabs tested positive for C. albicans and showed drug
      resistance to amphotericin B, fluconazole, itraconazole, and voriconazole on the
      fungal antibiogram. Targeted antifungal therapy with caspofungin was
      administrated in association with oral antibiotic therapy. Follow-up assessment
      at 1, 3, 6, 12, and 24 months did not show any infection or contracture relapse.
      CONCLUSIONS: This is the first report in the literature on a breast implant
      infection by a multidrug-resistant C. albicans. The study focused on the
      association between fungal contamination and capsular contracture and
      investigated the importance of a fungal antibiogram in cases of suspected
      prosthesis infection for performance of a targeted antifungal treatment.

PMID- 21717260
TI  - Evaluation of aesthetic abdominal surgery using a new clinical scale.
AB  - BACKGROUND: Evaluation of outcomes after aesthetic surgery still is a challenge
      in plastic surgery. The evaluation frequently is based on subjective criteria.
      This study used a new clinical grading scale to evaluate aesthetic results for
      plastic surgeries to the abdomen. The method scores each of the following five
      parameters: volume of subcutaneous tissue, contour, excess of skin, aspect of the
      navel, and quality of the scar on the abdominal wall. The scale options are 0
      (poor), 1 (fair), and 2 (good), and the total rate can range from 0 to 10.
      METHODS: The study included 40 women ages 18-53 years. Of these 40 women, 20
      underwent traditional abdominoplasty, and 20 had liposuction alone.
      Preoperatively and at least 1 year later, photographic results were analyzed and
      scored by three independent plastic surgeons. RESULTS: In the abdominoplasty
      group, the average grade rose from 2.9+/-0.4 to 6.8+/-0.4 postoperatively. In the
      liposuction group, the average grade was 5.3+/-0.5 preoperatively and 7.7+/-0.4
      postoperatively. In both groups, the average postoperative grade was
      significantly higher than the preoperative grade. The mean scores for groups A
      and L were significantly different, demonstrating that the scale was sensitive in
      identifying different anatomic abnormalities in the abdomen. CONCLUSIONS: The
      rating scale used for the aesthetic evaluation of the abdomen was effective in
      the analysis of two different procedures: conventional abdominoplasty and
      liposuction. Abdominoplasty provided the greater gain according to a comparison
      of the pre- and postoperative scores.

PMID- 21717261
TI  - High-density hyaluronic acid for the treatment of HIV-related facial lipoatrophy.
AB  - BACKGROUND: Facial lipoatrophy is a stigmatizing hallmark of HIV. The injection
      of facial fillers has an essential role in the treatment of this condition. The
      objective of our study was to verify the safety and efficacy of a new formulation
      of high-density hyaluronic acid for the injectable treatment of HIV-related
      facial lipoatrophy. METHODS: We treated with high-density hyaluronic acid
      injections HIV patients affected by moderate to severe facial lipoatrophy and
      evaluated them at last follow-up, at a minimum of 36 weeks. Physician-related
      outcomes included pre-and post-treatment ultrasound measurement of the soft
      tissue thickness of the cheeks and qualitative assessment of aesthetic results by
      means of the Global Aesthetic Improvement Scale using pre- and post-treatment
      photos of the patients. Patient satisfaction outcomes were evaluated with the VAS
      face scale and Freiburg test. RESULTS: Fifty-four patients were studied. The
      median number of treatment sessions was 3 and the median length of treatment was
      5.5 months. The thickness of the soft tissues of the cheek increased
      significantly from 9.45 to 13.12 mm (p<0.0001). On the basis of the Global
      Aesthetic Improvement Scale, 87.5% of the patients were judged as "much improved"
      or "improved." Patient satisfaction at 1 year from the end of treatment was
      proven (VAS-face: 77.9; Freiburg questionnaire: 93.6% of patients were satisfied
      or very satisfied). Complications were limited to mild redness and swelling in
      the early postoperative period. CONCLUSION: Long-term improvement of facial
      contour and excellent patient satisfaction, in the absence of severe side
      effects, were obtained by the injection of high-density hyaluronic acid
      (STYLAGE(r) XL) in HIV patients with facial lipoatrophy.

PMID- 21717262
TI  - A plea to control medical tourism.
AB  - The growing phenomenon of patients seeking medical procedures abroad (MPA),
      formerly known as a medical tourism, is discussed. The dark side of the trend is
      exemplified by the tragic case of a 31-year-old Swedish woman who upon seeing a
      web advertisement went to Gdansk, Poland, to have breast augmentation. The
      operation was performed in an old hospital quite different from the modern
      hospital depicted in the ad. As a result of the grave mistakes in anesthetic care
      and lack of a postoperative recovery routine, the patient sustained severe brain
      injury because of prolonged hypoxia. Now, 6 months after the fateful operation,
      the patient is decorticated and has only vegetative functioning of the left side
      of the brain. Firm managers, who do not have any medical training, entice
      patients to believe that the doctors and the facilities abroad have the same
      technical and safety standards as at home. We question the gap in the law that
      allows a lay person to screen the candidates for surgery and decide who will
      operate and in what kind of environment. The trade in human organs is
      internationally banned but brokering operations on organs goes uncontrolled.
      Twenty other patients were operated on abroad at different facilities, but all
      told the same story: lack of adequate postoperative care, unfriendly nursing
      staff, and the feeling of abandonment upon the return home. The four facets of
      the ISAPS Patient Safety Diamond--the patient, the procedure, the facility, and
      the surgeon--are described. ISAPS decided to support the MPA policy with
      prescreening of the prospective patient, travel and medical insurance for the
      patient, and surgery abroad, but only if the surgeon is an ISAPS member in a
      fully accredited facility. This policy will be available first for UK residents
      who travel abroad for surgery, and later for patients and ISAPS surgeons
      worldwide. Many plastic surgeons have seen or heard of various tragedies or
      disasters following medical treatments in foreign countries. We propose to raise
      the plea for the introduction of legislation forbidding lay persons to trade in
      or act as an intermediary or broker of medical treatments abroad.

PMID- 21717263
TI  - Intra-arterial therapy for acute ischemic stroke.
AB  - Intra-arterial therapy (IAT) for acute ischemic stroke refers to endovascular
      catheter-based approaches to achieve recanalization using mechanical clot
      disruption, locally injected thrombolytic agents or both. IAT may be used in
      addition to intravenous tissue plasminogen activator (tPA) or in patients who do
      not qualify for tPA, usually because they are outside the approved 3-h timeframe
      window or have contraindications, such as elevated international normalized ratio
      or partial thromboplastin time. Recanalization rates correlate with clinical
      improvement, and with the newest catheters it is possible to achieve
      recanalization in roughly 80% of patients treated. However, while the catheters
      are approved by the Food and Drug Administration, there are still no randomized
      trial data demonstrating the role of current IAT therapy vs either tPA or
      standard management. IAT is reserved for patients with large artery occlusions in
      the basilar, distal carotid, or proximal middle cerebral arteries. Imaging the
      penumbra using magnetic resonance imaging or computed tomographic perfusion is
      currently the most frequently used way to identify patients who might benefit.
      However, the imaging and clinical criteria for identifying which patients
      benefit, and perhaps more importantly those who will do poorly despite IAT,
      remain unclear.

PMID- 21717264
TI  - Single-incision laparoscopic surgery in a survival animal model using a
      transabdominal magnetic anchoring system.
AB  - BACKGROUND: Though single-incision laparoscopic surgery (SILS) can reduce
      operative scarring and facilitates postoperative recovery, it does have some
      limitations, such as reduction in instrument working, difficulty in
      triangulation, and collision of instruments. To overcome these limitations,
      development of new instruments is needed. The aim of this study is to evaluate
      the feasibility and safety of a magnetic anchoring system in performing SILS
      ileocecectomy. METHODS: Experiments were performed in a living dog model. Five
      dogs (26.3-29.2 kg) underwent ileocecectomy using a multichannel single port
      (OCTO port; Darim, Seoul, Korea). The port was inserted at the umbilicus and
      maintained a CO(2) pneumoperitoneum. Two magnet-fixated vascular clips were
      attached to the colon using an endoclip applicator, and it was held together
      across the abdominal wall by using an external handheld magnet. The cecum was
      then retracted in an upward direction by moving the external handheld magnet, and
      the mesocolon was dissected with Ultracision((r)). Extracorporeal functional end
      to-end anastomosis was done using a linear stapler. All animals survived during
      the observational period of 2 weeks, and then re-exploration was performed under
      general anesthesia for evaluation of intra-abdominal healing and complications.
      RESULTS: Mean operation time was 70 min (range 55-100 min), with each subsequent
      case taking less time. The magnetic anchoring system was effective in achieving
      adequate exposure in all cases. All animals survived and convalesced normally
      without evidence of clinical complication during the observation period. At re
      exploration, all anastomoses were completely healed and there were no
      complications such as abscess, bleeding or organ injury. CONCLUSIONS: SILS
      ileocecectomy using a magnetic anchoring system was safe and effective in a dog
      model. The development of magnetic anchoring systems may be beneficial for
      overcoming the limitations of SILS.

PMID- 21717265
TI  - Clinical outcomes of atypical extra-esophageal reflux symptoms following
      laparoscopic antireflux surgery.
AB  - INTRODUCTION: While it is well established that antireflux surgery is effective
      in relieving typical gastroesophageal reflux disease (GERD) symptoms such as
      heartburn and regurgitation, it is currently unclear whether atypical symptoms
      (cough, hoarseness, wheeze) foreshadow a less satisfactory outcome following
      laparoscopic antireflux surgery (LARS). The purpose of this study is to
      critically analyze the clinical outcomes of atypical symptoms in patients
      undergoing LARS. METHODS: Patients scheduled for LARS for GERD were prospectively
      enrolled over a 7-year period; all subjects underwent preoperative high
      resolution manometry (HRM) and had evidence of GERD on ambulatory pH study.
      Cough, wheeze, and hoarseness were considered atypical symptoms. During
      preoperative and postoperative examinations, patients completed detailed foregut
      symptomatology questionnaires, using both 5-point Likert and 10-point visual
      analog scales (VAS) to document typical as well as atypical symptoms. Atypical
      symptom burden was calculated as a sum of VAS for the three atypical symptoms,
      termed the atypical score (ATS). HRM patterns were grouped into normal, spastic,
      and hypomotile. Statistical significance (p < 0.05) was determined using paired t
      test, and analysis of variance with post hoc least significant difference (LSD).
      RESULTS: One hundred thirteen patients (age 49 +/- 1.26 years, range 20-84 years,
      M:F 47:66) with mean follow-up of 28 +/- 2.31 months (range 1-92 months)
      fulfilled inclusion criteria, having mean modified DeMeester score of 45.5 +/-
      2.78. Heartburn was noted in 84.1%, while atypical symptoms of some degree were
      reported by 92.0% (104 patients). Heartburn improved from a preoperative score of
      7.1 +/- 0.54 to 0.9 +/- 0.24 after LARS, and ATS improved from 8.9 +/- 0.71 to
      2.2 +/- 0.42. Significant improvements were noted for all atypical symptoms
      analyzed (p < 0.0001 for each). Improvement in atypical symptoms was least in the
      presence of hypomotility features on HRM (21.7% improvement), compared with
      normal motility (72.4%) and spastic features (83.9%). Preoperative atypical score
      (p < 0.0001) and esophageal hypomotility (p = 0.04) demonstrated a linear
      relationship with postoperative atypical score. CONCLUSIONS: In an unselected
      cohort of patients undergoing LARS, atypical GERD symptoms improved as
      significantly as typical symptoms. Symptom improvement was significantly lower in
      the presence of esophageal hypomotility and with higher symptomatic state.
      Therefore, patients with severe atypical symptoms or hypomotile esophagus may not
      achieve the same clinical satisfaction from LARS.

PMID- 21717266
TI  - Conducting behavioral research on Amazon's Mechanical Turk.
AB  - Amazon's Mechanical Turk is an online labor market where requesters post jobs and
      workers choose which jobs to do for pay. The central purpose of this article is
      to demonstrate how to use this Web site for conducting behavioral research and to
      lower the barrier to entry for researchers who could benefit from this platform.
      We describe general techniques that apply to a variety of types of research and
      experiments across disciplines. We begin by discussing some of the advantages of
      doing experiments on Mechanical Turk, such as easy access to a large, stable, and
      diverse subject pool, the low cost of doing experiments, and faster iteration
      between developing theory and executing experiments. While other methods of
      conducting behavioral research may be comparable to or even better than
      Mechanical Turk on one or more of the axes outlined above, we will show that when
      taken as a whole Mechanical Turk can be a useful tool for many researchers. We
      will discuss how the behavior of workers compares with that of experts and
      laboratory subjects. Then we will illustrate the mechanics of putting a task on
      Mechanical Turk, including recruiting subjects, executing the task, and reviewing
      the work that was submitted. We also provide solutions to common problems that a
      researcher might face when executing their research on this platform, including
      techniques for conducting synchronous experiments, methods for ensuring high
      quality work, how to keep data private, and how to maintain code security.

PMID- 21717267
TI  - Russian norms for name agreement, image agreement for the colorized version of
      the Snodgrass and Vanderwart pictures and age of acquisition, conceptual
      familiarity, and imageability scores for modal object names.
AB  - The aim of the present study was to provide Russian normative data for the
      Snodgrass and Vanderwart (Behavior Research Methods, Instruments, & Computers,
      28, 516-536, 1980) colorized pictures (Rossion & Pourtois, Perception, 33, 217
      236, 2004). The pictures were standardized on name agreement, image agreement,
      conceptual familiarity, imageability, and age of acquisition. Objective word
      frequency and objective visual complexity measures are also provided for the most
      common names associated with the pictures. Comparative analyses between our
      results and the norms obtained in other, similar studies are reported. The
      Russian norms may be downloaded from the Psychonomic Society supplemental
      archive.

PMID- 21717268
TI  - CDF-XL: computing cumulative distribution functions of reaction time data in
      Excel.
AB  - In experimental psychology, central tendencies of reaction time (RT)
      distributions are used to compare different experimental conditions. This
      emphasis on the central tendency ignores additional information that may be
      derived from the RT distribution itself. One method for analysing RT
      distributions is to construct cumulative distribution frequency plots (CDFs;
      Ratcliff, Psychological Bulletin 86:446-461, 1979). However, this method is
      difficult to implement in widely available software, severely restricting its
      use. In this report, we present an Excel-based program, CDF-XL, for constructing
      and analysing CDFs, with the aim of making such techniques more readily
      accessible to researchers, including students (CDF-XL can be downloaded free of
      charge from the Psychonomic Society's online archive). CDF-XL functions as an
      Excel workbook and starts from the raw experimental data, organised into three
      columns (Subject, Condition, and RT) on an Input Data worksheet (a point-and
      click utility is provided for achieving this format from a broader data set). No
      further preprocessing or sorting of the data is required. With one click of a
      button, CDF-XL will generate two forms of cumulative analysis: (1) "standard"
      CDFs, based on percentiles of participant RT distributions (by condition), and
      (2) a related analysis employing the participant means of rank-ordered RT bins.
      Both analyses involve partitioning the data in similar ways, but the first uses a
      "median"-type measure at the participant level, while the latter uses the mean.
      The results are presented in three formats: (i) by participants, suitable for
      entry into further statistical analysis; (ii) grand means by condition; and (iii)
      completed CDF plots in Excel charts.

PMID- 21717269
TI  - Adaptive response of children and adolescents with autism to the 2009 earthquake
      in L'Aquila, Italy.
AB  - The literature offers no descriptions of the adaptive outcomes of people with
      autism spectrum disorder (ASD) after natural disasters. Aim of this study was to
      evaluate the adaptive behaviour of participants with ASD followed for 1 year
      after their exposure to the 2009 earthquake in L'Aquila (Italy) compared with an
      unexposed peer group with ASD, by administering the Italian form of the Vineland
      Adaptive Behaviour Scales (VABS) at baseline, 6 months and 1 year after the
      earthquake. Exposed participants declined dramatically in their adaptive
      behaviour during the first months after the earthquake (p < 0.01 for all VABS
      dimensions). However, immediate intensive post-disaster intervention allowed
      children and adolescents with autism showing a trend towards partial recovery of
      adaptive functioning.

PMID- 21717270
TI  - Phospholipid hydroperoxide glutathione peroxidase gene is regulated via an
      estrogen and estrogen receptor signaling in cultured mouse fetuses.
AB  - Although it has been suggested that the transcription of phospholipid
      hydroperoxide glutathione peroxidase (PHGPx), an essential antioxidant
      selenoenzyme, may be affected by the estrogen state in mammals, the direct
      mechanism underlying the regulation of the PHGPx gene by estrogens in mammalian
      tissues remains to be clearly elucidated. In this study, we evaluated the
      expression of the PHGPx mRNA in cultured mouse fetuses (embryonic days 8.5-10.5)
      exposed to 17beta-estradiol (E(2); 0.1, 1, 10, 100, and 1,000 ng/ml); estrogen
      receptor (ER) agonists [propyl pyrazole triol (PPT, an ERalpha-selective ligand,
      1 MUl/ml) and diarylpropionitrile (DPN, an ERbeta-selective ligand, 1 MUl/ml)];
      and/or ER antagonist [ICI 182,780 (ICI, 1 MUl/ml)] using a whole embryo culture
      system. E(2)-alone treatment significantly stimulated the expressions of both
      ERalpha and ERbeta mRNAs in all the cultured fetuses (p < 0.05), although the
      ERbeta mRNA levels were higher than ERalpha mRNA. PHGPx mRNA expression was
      significantly increased in all the fetuses treated with E(2) (1-1,000 ng/ml),
      PPT, and DPN (p < 0.05). Furthermore, pretreatment with ICI completely blocked
      the E(2)-induced PHGPx mRNA expression in the fetuses. In addition, the mRNA
      levels of cytosolic GPx, the other intracellular antioxidant selenoenzyme, did
      not differ significantly from the controls by an exposure to those agents. These
      results suggest that the PHGPx gene is regulated via an estrogen and ER signal
      pathway in the cultured mouse fetus.

PMID- 21717271
TI  - Different doses of bone morphogenetic protein 4 promote the expression of early
      germ cell-specific gene in bone marrow mesenchymal stem cells.
AB  - Bone morphogenetic protein (BMP)-4 has a crucial role on primordial germ cells
      (PGCs) development in vivo which can promote stem cell differentiation to PG-like
      cells. In this study, we investigated the expression of Mvh as one of the
      specific genes in primordial germ cells after treatment with different doses of
      BMP4 on bone mesenchymal stem cells (BMSCs)-derived PGCs. Following isolation of
      BMSCs from male mouse femur and tibia, cells were cultured in medium for 72 h.
      Passage 4 murine BMSCs were characterized by CD90, CD105, CD34, and CD45 markers
      and osteo-adipogenic differentiation. Different doses of BMP4 (0, 0.01, 0.1, 1,
      5, 25, 50, and 100 ng/ml) were added to BMSCs for PGCs differentiation during 4
      days culture. Viability percent, proliferation rates, and expression of Mvh gene
      were analyzed by RT-qPCR. Data analysis was done with ANOVA test. CD90(+),
      CD105(+), CD34(-), and CD45(-) BMSCs were able to differentiate to osteo
      adipogenic lineages. The results revealed that proliferation rate and viability
      percent were raised significantly (p <= 0.05) by adding 1, 5, 25 ng/ml of BMP4
      and there were decreased to the lowest rate after adding 100 ng/ml BMP4 (p <=
      0.05). There were significant up regulation (p <= 0.05) in Mvh expression between
      25, 50, and 100 ng/ml BMP4 with other doses. So the selective dose of BMP-4 for
      treatment during 4-day culture was 25 ng/ml. The results suggest that addition of
      25 ng/ml BMP4 had the best effects based on gene-specific marker expression.

PMID- 21717272
TI  - Acute stress in patients with brain cancer during primary care.
AB  - PURPOSE: This study investigated whether diagnosis and neurosurgical removal of a
      brain tumour induced Acute Stress Disorder (ASD) in adults. We also aimed to
      identify factors associated with the development of ASD in this specific patient
      group and setting. METHODS: Forty-seven consecutive patients with intracranial
      neoplasms completed a variety of self-report questionnaires and underwent a
      structured clinical interview (SCID) within the first 4 weeks after tumour
      detection on average 1 week after neurosurgical treatment. Moreover, the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), A1
      and A2 criterion and thus the characteristics of the traumatic event were
      explored in detail. RESULTS: ASD symptoms were common. Twenty-three percent of
      the patients met stringent criteria of ASD and another 4% suffered from
      subsyndromal ASD. Predisposing factors previously reported in literature with the
      exception of previous trauma could not be identified in this study (e.g., sex,
      age, intelligence). CONCLUSION: It has been critically discussed whether the
      diagnosis of ASD is appropriate in cancer patients due to the often future
      related nature of cancer-related traumatic events. The diagnosis of ASD was
      justified in the vast majority of affected patients due to the specific, acute
      and past traumatic experiences in concordance with the DSM and International
      Statistical Classification of Diseases and Related Health Problems (ICD) trauma
      definitions. Thus, ASD is a common and relevant psychiatric comorbidity in
      patients with brain tumours. Our data highlight both the need for the routine
      psychological assessment as well as of psychosocial support in this early
      treatment phase.

PMID- 21717273
TI  - What kind of cancer information do Internet users need?
AB  - PURPOSE: The Internet becomes one of the most effective communication media in
      healthcare. This study aimed to evaluate the cancer information sources and the
      needs of various types of Internet users. METHODS: We conducted a survey on the
      National Cancer Information Center website from April 2007 to December 2007. Of
      the 170,746 visitors, 507 responded to the survey, and the data were analyzed
      according to self-identified user types. RESULTS: The participants identified
      themselves as patients (17%), caregivers (32%), healthcare professionals (21%),
      or general public (30%). Different user groups looked for different cancer
      information. Totally, 72.1% patients and 82% caregivers wanted the information
      about treatment, and 71.3% of healthcare professionals and 88.2% of the general
      public wanted the information related to 'prevention & diagnosis.' Healthcare
      professionals had a higher need for "statistics & research" information compared
      to other Internet user groups. The Internet was reported as the most common
      source of cancer information for all user groups. CONCLUSIONS: The type of cancer
      information needed and the usefulness of the information acquired on the Internet
      varied among the different types of user groups, suggesting that Web-based cancer
      information should be tailored to each type of user.

PMID- 21717275
TI  - Good health policy: the marriage of reimbursement and professional societies'
      appropriate use criteria.

PMID- 21717276
TI  - Characterization of mechanical dyssynchrony measured by gated single photon
      emission computed tomography phase analysis after acute ST-elevation myocardial
      infarction.
AB  - BACKGROUND: Left ventricular dyssynchrony is an adverse consequence of ST
      elevation myocardial infarction (STEMI) and bears an unfavorable prognosis.
      Mechanical dyssynchrony as measured by phase analysis from gated single photon
      emission computed tomography (GSPECT) correlates well with other imaging methods
      of assessing dyssynchrony but has not been studied in STEMI. We hypothesized that
      systolic dyssynchrony as measured by GSPECT would correlate with adverse
      remodeling after STEMI. METHODS: In 28 subjects suffering STEMI, GSPECT with
      technetium-99m sestamibi was performed immediately after presentation (day 5) and
      remotely (6 months). Parameters of left ventricular dyssynchrony (QRS width,
      histogram bandwidth (HBW) and phase standard deviation (PSD)) were measured from
      GSPECT using the Emory Cardiac Toolbox. Left ventricular volumes, ejection
      fraction (LVEF) and infarct size were also assessed. RESULTS: After successful
      primary percutaneous coronary intervention to the infarct-related artery,
      subjects had an LVEF of 46.4% +/- 11% and a resting perfusion defect of 27.4% +/-
      16% at baseline. Baseline QRS width was normal (91.5 +/- 17.5 ms). Subjects with
      STEMI had dyssynchrony compared with a cohort of 22 normal subjects (age 57.2 +/-
      10.6 years, <5% perfusion defect) by both HBW (100.3 degrees  +/- 70.7 degrees 
      vs 26.5 degrees  +/- 5.3 degrees , P < .0001) and PSD (35.3 degrees  +/- 16.9
      degrees  vs 7.9 degrees  +/- 2.1 degrees , P < .0001). Baseline HBW correlated
      with resting perfusion defect size (r = 0.67, P < .001), end-systolic volume (r =
      0.72, P < .001), end-diastolic volume (r = 0.63, P = .001), and inversely with
      LVEF (r = -0.74, P < .001). HBW and PSD improved over the follow-up period (-24.1
      +/- 35.9 degrees, P = .003 and -8.7 degrees  +/- 14.6 degrees , P = .006,
      respectively), and improvement in HBW correlated with reduction in LV end
      systolic volumes (r = 0.43, P = .034). Baseline HBW and PSD, however, did not
      independently predict LVEF at 6 months follow-up. CONCLUSIONS: After STEMI,
      subjects exhibit mechanical dyssynchrony as measured by GSPECT phase analysis
      without evidence of electrical dyssynchrony. Improvement in mechanical
      dyssynchrony correlates with beneficial ventricular remodeling. The full
      predictive value of this measure in post-infarct patients warrants further study.

PMID- 21717277
TI  - The role of anesthesiologists in promoting smoking cessation.

PMID- 21717278
TI  - Evaluation of plumbagin and its derivative as potential modulators of redox thiol
      metabolism of Leishmania parasite.
AB  - Trypanothione and trypanothione reductase (TryR)-based redox metabolism found in
      Leishmania and other trypanosomatids exemplify the unique features of this group
      of organisms. Its absence in mammalian hosts, together with the sensitivity of
      trypanosomes against oxidative stress, makes this enzyme a unique target for
      exploitation for potential antileishmanial chemotherapeutics. Plumbagin, a plant
      derived naphthoquinone, is reported to possess antileishmanial properties by
      inhibiting TryR. We here report the kinetics of the inhibitory mechanism of
      plumbagin and its derivative, 2-methoxy 1, 4-naphthoquinone. Interestingly, apart
      from acting as inhibitor, these compounds also act as subversive substrates and
      subvert the physiological function of enzyme by converting it from an antioxidant
      to a prooxidant. Both naphthoquinones show a significant effect on redox
      homeostasis and results in increased reactive oxygen species, resulting in
      morphological changes and parasite death.

PMID- 21717280
TI  - D2 lymphadenectomy (over-D1 dissection) for advanced gastric cancer is an
      evidence-based procedure.

PMID- 21717279
TI  - Capillaria hepatica in man--an overview of hepatic capillariosis and spurious
      infections.
AB  - Capillaria hepatica (syn. for Calodium hepaticum) is a zoonotic nematode
      parasitizing in the livers of rodents as main hosts and in numerous other mammals
      including humans. It is the causative agent of the rare conditions of hepatic
      capillariosis and spurious C. hepatica infections in humans. In this review, 163
      reported cases of infestations with this parasite (72 reports of hepatic
      capillariosis, 13 serologically confirmed infestations and 78 observations of
      spurious infections) are summarized with an overview on the distribution,
      symptoms, pathology, diagnosis, serology and therapy of this rare human pathogen.

PMID- 21717281
TI  - The changes of pro-opiomelanocortin neurons in type 2 diabetes mellitus rats
      after ileal transposition: the role of POMC neurons.
AB  - BACKGROUND: Ileal transposition (IT) can effectively resolve obesity and improve
      type 2 diabetes. IT is associated with increased glucagon-like peptide 1
      secretion. The mechanisms mediating the effects of IT on obesity and diabetes
      remain undefined. Given the role of pro-opiomelanocortin neurons in energy
      balance, we sought to determine its potential role in these processes. METHODS:
      Twenty non-obese diabetic Goto-Kakizaki rats underwent either IT or sham
      operation. Various measures including food intake, body weight, fasting plasma
      glucose, glucagon-like peptide 1 level, activated pro-opiomelanocortin neuron
      number, and pro-opiomelanocortin mRNA expression were evaluated. RESULTS: The IT
      group demonstrated significantly improved plasma glucose homeostasis with
      increased glucagon-like peptide 1 secretion. The IT group ate less and
      demonstrated reduced body weight gain over time. These effects were also
      associated with increased central neuronal activity with increased pro
      opiomelanocortin and derivative gene expression in the hypothalamus and increased
      protein expression in the pituitary gland. CONCLUSIONS: More pro-opiomelanocortin
      neurons in the hypothalamus of diabetes rats were activated after ileal
      transposition. These data suggest a potential important role for pro
      opiomelanocortin neurons in the resolution of diabetes after IT.

PMID- 21717282
TI  - Impact of lymphatic vessel invasion on survival in curative resected gastric
      cancer.
AB  - BACKGROUND: Lymphatic vessel invasion (LV) has been regarded as a prognostic
      factor in some solid tumors. The aim was to clarify the impact of lymphatic
      vessel invasion on survival in curative resected gastric cancer. METHODS: In this
      retrospective study, we reviewed the records of 1,024 patients who underwent
      curative resection for gastric cancer. Among all of the studied patients, 285 of
      them (27.8%) had lymphatic vessel invasion. RESULTS: There were significant
      differences in tumor size, tumor location, depth of invasion, and lymph node
      metastasis (LN) between the patients with lymphatic vessel invasion and those
      without. The 5-year survival rates in patients were 80.1%, 59.2%, 40.9%, and
      30.5% for LN-LV-, LN-LV+, LN+LV-, and LN+LV+ group, respectively. Multivariate
      analysis revealed that age, tumor location, the depth of invasion, and lymph node
      metastasis were independent prognostic factors for curative resected gastric
      cancer. Lymphatic vessel invasion was not an independent prognostic factor in
      node-positive gastric cancer; however, it was true in node-negative gastric
      cancer. CONCLUSION: Lymphatic vessel invasion is one of the independent
      prognostic factors for node-negative gastric cancer after curative resection.

PMID- 21717283
TI  - Postoperative impedance-pH testing is unreliable after Nissen fundoplication with
      or without giant hiatal hernia repair.
AB  - INTRODUCTION: Combined 24-h multichannel intralumenal impedance-pH monitoring
      (MII-pH) is gaining popularity as a diagnostic tool for gastroesophageal reflux.
      Since the surgical reduction of hiatal hernias and creation of a fundoplication
      anatomically restores the gastroesophageal reflux barrier, one would assume that
      it effectively stops all reflux regardless of composition. Our aim is to evaluate
      the results of routine MII-pH testing in successful Nissen fundoplication
      patients. MATERIAL AND METHODS: Sixty-two patients with normal acid exposure,
      confirmed by 24-h pH testing, after Nissen fundoplication were evaluated with
      symptomatic questionnaire, esophageal manometry and MII-pH testing more than 6
      months after surgery. Patients were grouped into normal and abnormal based on
      postoperative impedance results. Patients with Nissen alone were separately
      compared to patients with Nissen + giant hiatal hernia (GHH). RESULTS: Twenty
      nine (47%) patients exhibited abnormal impedance after successful Nissen
      fundoplication. Abnormal impedance was associated with GHH repair, lower bolus
      pressures, and lower distal esophageal contraction amplitudes. CONCLUSION:
      Postoperative testing with the standard MII-pH catheters using published
      normative values seems to be clinically irrelevant. Clinicians should analyze the
      results of routine MII-pH testing in the setting of a fundoplication critically
      as the current technology is associated with a high false positive rate.

PMID- 21717284
TI  - Prevalence and clinical implications of positive serum anti-microsomal antibodies
      in symptomatic patients with ileal pouches.
AB  - BACKGROUND AND AIM: Autoimmune disorders (AID) have been shown to be associated
      with chronic antibiotic-refractory pouchitis (CARP). The role of anti-microsomal
      antibodies in ileal pouch disorders has not been investigated. The aims of the
      study were to investigate the prevalence of positive anti-microsomal antibody in
      symptomatic patients with ileal pouches and to investigate its clinical
      implications. METHODS: A total of 118 consecutive symptomatic patients with ileal
      pouches were included between January and October 2010. Anti-microsomal
      antibodies were measured at the time of presentation. Demographic, clinical, and
      laboratory characteristics were compared between patients with positive and
      negative anti-microsomal antibody. RESULTS: There were 14 patients (11.9%) with
      positive serum anti-microsomal antibody. The mean age of patients in the antibody
      positive and negative groups were 41.8 +/- 14.4 and 42.0 +/- 14.0 years,
      respectively (p = 0.189). All 14 patients in the antibody positive group (100%)
      had some form of AID, as compared to 20 patients (19.2%) in the antibody negative
      group (p < 0.001). Four (28.6%) patients in the antibody positive group had at
      least one AID in addition to Hashimoto's thyroiditis in contrast to four (3.8%)
      in the antibody negative group (p = 0.003). In addition, five (35.7%) patients
      had associated primary sclerosing cholangitis (PSC) in the antibody positive
      group compared to nine (8.7%) in the antibody negative group (p = 0.012). Eleven
      patients (78.6%) in the antibody positive group required steroids for treatment
      of pouch related symptoms in contrast to 26/104 (25%) patients in the antibody
      negative group (p = 0.002). CONCLUSIONS: Anti-microsomal antibodies were common
      in pouch patients presenting with symptoms. Patients with positive anti
      microsomal antibodies were much more likely to have concurrent AID and PSC. These
      patients were more likely to require therapy with steroids.

PMID- 21717285
TI  - Identifiability of large phylogenetic mixture models.
AB  - Phylogenetic mixture models are statistical models of character evolution
      allowing for heterogeneity. Each of the classes in some unknown partition of the
      characters may evolve by different processes, or even along different trees. Such
      models are of increasing interest for data analysis, as they can capture the
      variety of evolutionary processes that may be occurring across long sequences of
      DNA or proteins. The fundamental question of whether parameters of such a model
      are identifiable is difficult to address, due to the complexity of the
      parameterization. Identifiability is, however, essential to their use for
      statistical inference.We analyze mixture models on large trees, with many mixture
      components, showing that both numerical and tree parameters are indeed
      identifiable in these models when all trees are the same. This provides a
      theoretical justification for some current empirical studies, and indicates that
      extensions to even more mixture components should be theoretically well behaved.
      We also extend our results to certain mixtures on different trees, using the same
      algebraic techniques.

PMID- 21717286
TI  - Presymptomatic testing for neurogenetic diseases in Brazil: assessing who seeks
      and who follows through with testing.
AB  - Diagnostic tests are available to detect several mutations related to adult
      onset, autosomal dominant, neurodegenerative diseases. We aimed to describe our
      experience in a presymptomatic testing program run by the Brazilian Public Health
      System from 1999 to 2009. A total of 184 individuals were eligible for
      presymptomatic testing due to a risk for spinocerebellar ataxia (SCA) - SCA3
      (80%), Huntington's disease (11.9%), familial amyloidotic neuropathy (4.3%),
      SCA1, SCA2, SCA6, or SCA7. Most were women (70%), married (54%), and had children
      prior to presymptomatic testing (67%). Their mean age at entrance was 34 (SD = 11
      years). Educational level was above the average Brazilian standard. After receipt
      of genetic counseling, 100 individuals (54%) decided to undergo testing; of
      these, 51 were carriers. Since no individual returned for post-test psychological
      evaluation, we conducted a subsequent survey, unrelated to test disclosures. We
      contacted 57 individuals of whom 31 agreed to participate (24 had been tested, 7
      had not). Several ascertainment concerns relating to these numerous losses
      prevented us from generalizing our results from this second survey. We concluded
      that: decision-making regarding presymptomatic testing seems to be genuinely
      autonomous, since after genetic counseling half the individuals who asked for
      presymptomatic testing decided in favor and half decided against it; general
      characteristics of Brazilians who sought presymptomatic testing were similar to
      many European samples studied previously; and individuals at risk for SCA3 may be
      at greater risk of depression. Although no clear-cut reason emerged for rejection
      of follow-up psychological sessions after presymptomatic testing, this finding
      suggests adjustments to our presymptomatic testing program are necessary.

PMID- 21717287
TI  - Diversity and general student scholarship recipient essays: 2010 National Society
      of Genetic Counselors Membership Committee.
AB  - In an effort to increase the diversity of the membership of the National Society
      of Genetic Counselors (NSGC), the Membership Committee provided two $500
      scholarships to genetic counseling students planning to attend the NSGC AEC
      meeting in Dallas, Texas in October 2010. Requirements for applicants of both
      scholarships included enrollment in the fall of 2010, good standing at an
      accredited genetic counseling training program, and NSGC membership or plans to
      join in 2011. Students who are from communities underrepresented in the NSGC,
      including, but not limited to, those of minority cultural/ethnic backgrounds and
      those with disabilities were eligible to apply for the "Diversity" scholarship.
      Students from all backgrounds who have an interest in diversity issues were
      eligible to apply for the "General" scholarship. Applicants wrote essays 1000
      words or less answering the following questions: How has your identity as a
      member of a group underrepresented in the genetic counseling profession affected
      your pursuit of this career? What do you feel is lacking in genetic counseling to
      address the issues of underrepresented groups? What strategies do you recommend
      for addressing these issues and/or increasing diversity? Why do you think
      diversity is an important issue for the field of genetic counseling? What
      strategies do you recommend to attract and retain students, especially those from
      underrepresented populations, into the field of genetic counseling? How do you
      envision contributing to these strategies? The essays by the award recipients
      elucidated interesting perspectives and ideas for increasing diversity in the
      genetic counseling profession.

PMID- 21717288
TI  - Faster target selection in preview visual search depends on luminance onsets:
      behavioral and electrophysiological evidence.
AB  - To investigate how target detection in visual search is modulated when a subset
      of distractors is presented in advance (preview search), we measured search
      performance and the N2pc component as an electrophysiological marker of
      attentional target selection. Targets defined by a color/shape conjunction were
      detected faster and the N2pc emerged earlier in preview search relative to a
      condition in which all items were presented simultaneously. Behavioral and
      electrophysiological preview benefits disappeared when stimuli were equiluminant
      with their background, in spite of the fact that targets were feature singletons
      among the new items in preview search. The results demonstrate that previewing
      distractors expedites the spatial selection of targets at early sensory
      perceptual stages, and that these preview benefits depend on rapid attentional
      capture by luminance onsets.

PMID- 21717289
TI  - Plasma therapy for atypical haemolytic uraemic syndrome associated with
      heterozygous factor H mutations.
AB  - Atypical haemolytic uraemic syndrome (aHUS) is frequently associated with
      mutations in the gene encoding complement factor H (CFH). The clinical response
      to plasma therapy in aHUS is variable. We present here our experience of plasma
      therapy in three aHUS patients with CFH mutations. Three children presented aged
      4, 22 and 6 months (patients 1-3 respectively) in acute kidney injury requiring
      dialysis. Plasma therapy consisting of plasma filtration (patient 1) or plasma
      exchange (PEX; patients 2 and 3) was commenced early following presentation. This
      resulted in aHUS remission and cessation of dialysis after 2 weeks, 9 days and 2
      weeks respectively. Relapses were common and associated with increasing the
      interval between PEX, but all responded to intensification of PEX therapy.
      Patient 1 recovered 50% of renal function after first presentation. She had four
      relapses and started peritoneal dialysis 41 months after presentation. Mutation
      screening of CFH showed a missense mutation (c.3546 G > T, p.Arg1182Ser) in exon
      23. PEX in patient 2 was slowly tapered over 4 months to fortnightly sessions,
      but she relapsed when PEX was extended to every 4 weeks. Renal function remained
      normal 12 months post-presentation. Mutation screening of CFH showed a mutation
      in exon 23 (c.3590 T > C, p.Val1197Ala) and two additional sequence variants in
      exons 3 and 4. Patient 3 had two relapses associated with intercurrent illnesses
      concurrent with reducing PEX to weekly doses. Renal function was normal 5 months
      post-presentation. All three patients showed a good response to PEX with improved
      renal function both initially and following a relapse. Further research is
      necessary to determine the best maintenance strategy to delay or prevent end
      stage kidney disease.

PMID- 21717290
TI  - Acoustic basis of directional acuity in laboratory mice.
AB  - The acoustic basis of auditory spatial acuity was investigated in CBA/129 mice by
      relating patterns of behavioral errors to directional features of the head
      related transfer function (HRTF). Behavioral performance was assessed by training
      the mice to lick a water spout during sound presentations from a "safe" location
      and to suppress the response during presentations from "warning" locations.
      Minimum audible angles (MAAs) were determined by delivering the safe and warning
      sounds from different locations in the inter-aural horizontal and median vertical
      planes. HRTFs were measured at the same locations by implanting a miniature
      microphone and recording the gain of sound energy near the ear drum relative to
      free field. Mice produced an average MAA of 31 degrees  when sound sources were
      located in the horizontal plane. Acoustic measures indicated that binaural inter
      aural level differences (ILDs) and monaural spectral features of the HRTF change
      systematically with horizontal location and therefore may have contributed to the
      accuracy of behavioral performance. Subsequent manipulations of the auditory
      stimuli and the directional properties of the ear produced errors that suggest
      the mice primarily relied on ILD cues when discriminating changes in azimuth. The
      MAA increased beyond 80 degrees  when the importance of ILD cues was minimized by
      testing in the median vertical plane. Although acoustic measures demonstrated a
      less robust effect of vertical location on spectral features of the HRTF, this
      poor performance provides further evidence for the insensitivity to spectral cues
      that was noted during behavioral testing in the horizontal plane.

PMID- 21717291
TI  - Nocturnal ranging by a diurnal primate: are ring-tailed lemurs (Lemur catta)
      cathemeral?
AB  - Cathemerality, an activity pattern comprised of distinct periods of diurnal and
      nocturnal activity, is a trait found among several of the Malagasy strepsirhines
      and one species of Aotus. Because occasional anecdotal reports suggest that some
      diurnal primates can be active at night, I investigated the possibility of
      nocturnal ranging behavior in the ring-tailed lemur (Lemur catta) by using global
      positioning system (GPS) collars programmed to collect data across a 24-h period.
      Five individuals in a provisioned, free-ranging L. catta colony on St. Catherines
      Island, Georgia, USA, wore GPS collars across 1 week of the mating season.
      Results revealed that night ranging behavior occurred between the h of 1900 and
      0530. An evaluation of the effect of moonlight on nocturnal activity showed that
      a greater rate of travel occurred during moonlit periods as opposed to periods
      when the moon had not yet risen. Distance travelled at night decreased across the
      deployment period, likely because of a decrease in available moonlight over time,
      as the lemurs were collared during a waning moon. Fewer mating opportunities over
      time may have also been responsible for the decrease in night ranging, because
      the number of females in estrus declined across the deployment period. Future
      research is needed to separate the effects of moonlight and mating activity on
      night ranging in this species, as well as to evaluate whether L. catta in
      Madagascar show night ranging similar to L. catta on SCI. These data raise the
      possibility that L. catta may be cathemeral, with an activity pattern fluctuating
      between diurnality and cathemerality in accordance with shifts in environmental
      conditions.

PMID- 21717292
TI  - Drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV
      associated dementia.
AB  - Although the incidence of HIV-associated dementia (HAD) has declined, HIV
      associated neurocognitive disorders (HAND) remain a significant health problem
      despite use of highly active antiretroviral therapy. In addition, the incidence
      and/or severity of HAND/HAD are increased with concomitant use of drugs of abuse,
      such as cocaine, marijuana, and methamphetamine. Furthermore, exposure to most
      drugs of abuse increases brain levels of dopamine, which has been implicated in
      the pathogenesis of HIV. This review evaluates the potential role of dopamine in
      the potentiation of HAND/HAD by drugs of abuse. In the brain, multiplication of
      HIV in infected macrophages/microglia could result in the release of HIV proteins
      such as gp120 and Tat, which can bind to and impair dopamine transporter (DAT)
      functions, leading to elevated levels of dopamine in the dopaminergic synapses in
      the early asymptomatic stage of HIV infection. Exposure of HIV-infected patients
      to drugs of abuse, especially cocaine and methamphetamine, can further increase
      synaptic levels of dopamine via binding to and subsequently impairing the
      function of DAT. This accumulated synaptic dopamine can diffuse out and activate
      adjacent microglia through binding to dopamine receptors. The activation of
      microglia may result in increased HIV replication as well as increased production
      of inflammatory mediators such as tumor necrosis factor (TNF)-alpha and
      chemokines. Increased HIV replication can lead to increased brain viral load and
      increased shedding of HIV proteins, gp120 and Tat. These proteins, as well as TNF
      alpha, can induce cell death of adjacent dopaminergic neurons via apoptosis.
      Autoxidation and metabolism of accumulated synaptic dopamine can lead to
      generation of reactive oxygen species (hydrogen peroxide), quinones, and
      semiquinones, which can also induce apoptosis of neurons. Increased cell death of
      dopaminergic neurons can eventually lead to dopamine deficit that may exacerbate
      the severity and/or accelerate the progression of HAND/HAD.

PMID- 21717296
TI  - Frequencies of perianal fistula types using two classification systems.
AB  - PURPOSE: The aims of this study were to determine the frequencies of the perianal
      fistula subtypes according to the Parks and St. James's University Hospital
      (SJUH) classification systems and to evaluate the adequacy of these two systems
      for classifying and reporting perianal fistulas. MATERIALS AND METHODS: Magnetic
      resonance imaging examinations of 52 patients (44 men, 8 women) with perianal
      fistula were reviewed retrospectively. The fistulas were classified according to
      the Parks and SJUH classification systems. RESULTS: According to the Parks
      system, 13 patients had intersphincteric (25%), 36 had transsphincteric (69.23%),
      and 2 had (3.84%) extrasphincteric fistulas. Only one fistula (a subsphincteric
      fistula) (1.92%) could not be classified. According to the SJUH system, 10
      patients had grade 1 (19.23%), 2 patients had grade 2 (3.84%), 13 patients had
      grade 3 (25%), 21 patients had grade 4 (40.38%), and 5 patients had grade 5
      (9.61%) perianal fistulas. The one (and only) subsphincteric fistula was left
      unclassified. CONCLUSION: The most common types are transsphincteric and
      intersphincteric fistulas. Although the two most commonly used classification
      systems are adequate for describing most perianal fistulas, there is a small
      percentage that is left unclassified.

PMID- 21717297
TI  - Various computed tomography findings of 2009 H1N1 influenza in 17 patients with
      relatively mild illness.
AB  - PURPOSE: We retrospectively analyzed the computed tomography (CT) findings of
      H1N1 virus infection in 17 patients with relatively mild illness. MATERIALS AND
      METHODS: From September 2009 to January 2010, a total of 17 patients with
      confirmed H1N1 infection were included in the study (mean age 30.7 years). All
      patients were managed as outpatients or required short hospitalization without
      ventilation assistance. The CT scans were assessed for the presence of nodules,
      ground glass opacity (GGO), consolidation, bronchial wall thickening,
      reticulation, effusion, and lymph node enlargement. Location and distribution
      were evaluated. RESULTS: The most frequent manifestation was a mixture of
      nodules, consolidation, and GGO (5/17, 29.4%). In one case there was a focal area
      of bronchiolitis (centrilobular nodules with tree-in-bud appearance), and 10 of
      17 cases (58.8%) showed bronchial wall thickening (findings of
      bronchitis/peribronchitis) and/or other abnormalities. In 16 of the 17 cases
      (94.1%) there were CT abnormalities with bilateral and random distribution
      without zonal predominance. Pleural effusions were seen in eight cases (47.1%).
      CONCLUSION: In contrast to several reports so far, CT findings of H1N1 virus
      infection in patients with mild illness are variable, including suggestive
      findings of inflammation involving large and/or small airways. This study showed
      various CT findings overlapping with other viral, atypical, or bacterial
      pneumonia and even cryptogenic organizing pneumonia.

PMID- 21717298
TI  - Cutaneous complications after transcatheter arterial treatment for hepatocellular
      carcinoma via the internal mammary artery: how to avoid this complication.
AB  - PURPOSE: To lower the rate of cutaneous complications after transcatheter
      arterial treatment for hepatocellular carcinoma (HCC) via the internal mammary
      artery (IMA) we retrospectively assessed the complications. MATERIALS AND
      METHODS: We reviewed cutaneous complications in 14 patients with 18 HCCs who had
      undergone 17 treatment procedures via the IMA, including selective transcatheter
      arterial infusion chemotherapy with Lipiodol (Lip-TAI) (n = 3), selective Lip-TAI
      + transcatheter arterial embolization (TAE) (n = 3), nonselective Lip-TAI (n =
      1), nonselective Lip-TAI + TAE (n = 5), and nonselective TAE (n = 5). The filling
      and nonfilling of subcutaneous vessels with Lipiodol was examined on
      postoperative computed tomography (CT) scans. RESULTS: Skin rash (n = 3) and
      ulceration (n = 1) occurred after 4 of 17 (24%) procedures: two of three
      selective Lip-TAI procedures and two of five nonselective Lip-TAI + TAE
      procedures. The doses of chemotherapeutic agents for tumor sizes in selective Lip
      TAI procedures were higher than those in selective Lip-TAI + TAE procedures.
      Cutaneous complications were encountered after two of three procedures with
      filling but not after any of eight procedures without filling. CONCLUSION: A
      lower dose of chemotherapeutic agents may be less risky when undertaking a
      selective procedure via the IMA for HCC. If nonselective, TAE alone may be less
      risky. Postoperative CT may be helpful for predicting cutaneous complications.

PMID- 21717299
TI  - Evaluation of image quality on a per-patient, per-vessel, and per-segment basis
      by noninvasive coronary angiography with 64-section computed tomography: dual
      source versus single-source computed tomography.
AB  - PURPOSE: The purpose of this study was to evaluate the image quality (IQ) of dual
      source CT (DSCT) versus single-source CT (SSCT). MATERIALS AND METHODS: A total
      of 100 patients underwent 64-section CT coronary angiography (50 DSCT, 50 SSCT).
      Three observers evaluated the IQ of each coronary segment using a four-point
      scale (1, excellent; 2, good; 3, fair; 4, no assessment). The IQ of DSCT coronary
      angiography was compared with SSCT coronary angiography on a per-patient, per
      vessel, and per-segment basis using the chi-squared test. RESULTS: The DSCT image
      quality score (IQS) was significantly lower on a per-patient basis and per-vessel
      basis for all vessels and on a per-segment basis for some segments (1, 2, 4PD,
      4AV, 7, 9, 11, 12, 13) compared with SSCT. The DSCT IQS was significantly lower
      for certain segments (2, 4PD, 11, 13) with high heart rates (>=70 beats/min). The
      DSCT IQS was significantly lower for certain segments (1, 2, 3, 4PD, 4AV, 7, 8,
      9, 10, 12, 13) with low heart rates (<70 beats/min). CONCLUSION: DSCT showed a
      significantly better IQ than SSCT, especially in patients with low heart rates.

PMID- 21717300
TI  - Dosimetric characteristics of the 192Ir high-dose-rate afterloading brachytherapy
      source.
AB  - PURPOSE: For the treatment of some cancerous tumors using brachytherapy, an
      American Association of Physicists in Medicine (AAPM) Task Group No. 43U1 report
      recommends that the dosimetric parameters of a new brachytherapy source must be
      determined in two experimental and Monte Carlo theoretical methods before using
      each new source clinically. This study presents the results of Monte Carlo
      calculations of the dosimetric parameters for a Ir2.A85-2 brachytherapy source
      design. MATERIALS AND METHODS: Version 5 of the (MCNP) Monte Carlo radiation
      transport code was used to calculate the dosimetry parameters around the source.
      RESULTS: The Monte Carlo calculated dose rate constant, Lambda, of the Ir2.A85-2
      source was found to be 1.113 +/- 0.033 cGyU(-1)h(-1). Also in this study, the
      line-source radial dose function, g ( l )(r) and the anisotropy function,
      F(r,theta), have been calculated at distances from 0.5 to 10 cm. The results of
      these calculations have been compared with the published data for the same
      source. CONCLUSION: All the results are in good concordance with previously
      published data, with a few exceptions in small angles and short distances. The
      dosimetric parameters calculated in this work can be used as input data in a
      treatment planning system (TPS) for exact brachytherapy treatment planning or to
      verify the calculations of the TPS used in brachytherapy.

PMID- 21717301
TI  - Should the dose of contrast medium be determined solely on the basis of body
      weight regardless of the patient's sex?
AB  - PURPOSE: The aim of this study was to evaluate prospectively the difference in
      contrast enhancement of liver parenchyma between male and female subjects when
      the total amount of contrast material is determined by the total body weight
      (TBW). MATERIALS AND METHODS: Computed tomography of the abdomen was performed
      with a total amount of iodine of 597 +/- 3.9 mg I/kg (mean +/- SD) over a mean +/
      SD total injection time of 30 +/- 0.26 s. Postcontrast attenuation during the
      portal venous phase was measured in the liver parenchyma, portal vein, and aorta.
      These values were summed for each and compared to those obtained before contrast
      injection. A total of 565 consecutive patients without a history of underlying
      liver/heart disease, including 297 male and 268 female subjects (age 16-92 years,
      mean 67 years) were scanned and analyzed using a two-tailed t-test. RESULTS: The
      difference between precontrast and the portal venous phase in the male subjects
      was 315.4 +/- 40.5 HU (mean +/- SD), and that in female subjects was 358.6 +/-
      44.8 HU. This difference was statistically significant (P < 0.0001). CONCLUSION:
      The contrast enhancement in females was 13.7% higher than that in males when the
      amount of iodine administered was based on the TBW. The difference can presumably
      be attributed to the difference in fat and muscle components. This result
      suggests that the amount of contrast material used in females should be reduced
      according to this difference.

PMID- 21717302
TI  - Newly developed compression fractures after percutaneous vertebroplasty:
      comparison with conservative treatment.
AB  - PURPOSE: The aim of this study was to investigate the incidence and timing of
      subsequent fractures in patients treated with and without percutaneous
      vertebroplasty (PVP). MATERIALS AND METHODS: We reviewed 794 patients who
      underwent 1500 PVPs with polymethylmethacrylate (PMMA) at our institution between
      January 1999 and December 2009. We also reviewed 349 patients with vertebral
      fractures who underwent conservative treatment without PVP between October 1999
      and December 2009 and compared the incidence and timing of subsequent fractures
      in the two groups. RESULTS: Among the 794 patients treated by PVP, 171 (21.5%)
      suffered 336 new vertebral fractures. Among the patients not treated by PVP, 82
      (23.5%) presented with 154 new fractures. There was no statistically significant
      difference (P = 0.46). Among the PVP-treated patients, one-half of new fractures
      occurred at a level adjacent to the treated level, and they occurred
      significantly sooner than nonadjacent level fractures (log-rank test, P < 0.01).
      CONCLUSION: PVP did not increase the incidence of new compression fractures
      compared with conservative treatment, but half of the new fractures at the
      adjacent vertebral bodies occurred sooner.

PMID- 21717303
TI  - Usefulness of multidetector computed tomography coronary venous angiography
      examination before cardiac resynchronization therapy.
AB  - PURPOSE: Cardiac resynchronization therapy (CRT) is a treatment option for
      selected heart failure patients. In this study, the aim was to evaluate the
      usefulness of noninvasive cardiac vein imaging using multidetector computed
      tomography (MDCT) angiography before CRT. MATERIALS AND METHODS: The MDCT scans
      of 34 patients (20 men; age range 47-65 years) with a history of cardiac failure
      were studied for CRT in two centers prospectively. The anatomy of the cardiac
      venous system, particularly the target veins [left marginal vein (LMV) and
      posterior vein of the left ventricle (PVLV)], was evaluated with noninvasive
      MDCT. RESULT: The coronary sinus, anterior interventricular vein, and posterior
      interventricular vein were observed in all patients. The PVLV was present in 30
      (88.2%) patients. The PVLV was chosen in 30 (88.2%) patients for CRT. If the PVLV
      had two or more branches, the widest branch was chosen for lead implantation. In
      four (11.7%) patients, the PVLV was absent and the LMV was chosen instead for
      lead implantation. In one patient (2.9%), partial thrombosis was detected in the
      coronary sinus with MDCT angiography. CONCLUSION: MDCT can be used to guide
      interventionalists for CRT by providing anatomical details of the cardiac venous
      system rapidly and noninvasively.

PMID- 21717304
TI  - Ruptured aneurysm with extravasation observed in four-dimensional computed
      tomography angiography.
AB  - We report a case of subarachnoid hemorrhage with a ruptured aneurysm in the
      anterior communicating artery. On multiphase dynamic contrast-enhanced four
      dimensional computed tomography angiography (4D CTA), we observed active bleeding
      from the aneurysm that manifested over time with a corkscrew-like, spindle-like,
      and lobulated appearance and nebulous enhancement, characteristics reported only
      individually previously. The volume data for 4D CTA is easy to obtain with newly
      developed multidetector-row computed tomography, and 4D CTA can be used for
      evaluating anatomical aspects, hemodynamics, and treatment selection in cases of
      a ruptured cerebral aneurysm.

PMID- 21717305
TI  - Distortion correction in whole-body imaging of live mice using a 1-Tesla compact
      magnetic resonance imaging system.
AB  - PURPOSE: The aim of this study was to establish a distortion correction
      applicable to whole-body imaging of live mice. MATERIALS AND METHODS: All
      magnetic resonance imaging (MRI) scans were acquired on a compact 1-T permanent
      magnet unit for mouse imaging using a T1-weighted, three-dimensional (3D) fast
      low-angle shot sequence. We assessed geometric distortion in MR images of a small
      3D grid phantom and determined 3D image transformations for distortion
      correction. The developed distortion correction was applied to MR images of the
      3D grid phantom acquired on another day, and the correction was validated. A two
      dimensional (2D) grid phantom was imaged with a mouse to investigate the
      applicability of the distortion correction to whole-body mouse imaging. RESULTS:
      Obvious geometric distortion was observed in the MR images of the 3D grid
      phantom. The application of the developed 3D phantom-based distortion correction
      reduced distortion in the images of the 3D grid phantom acquired on another day.
      Geometric distortion was observed in the MR images of the 2D grid phantom
      acquired together with the mouse. The 3D phantom-based correction decreased the
      distortion substantially, regardless of mouse positioning. CONCLUSION: The
      developed distortion correction can reduce distortion in whole-body imaging of
      live mice and may enhance the capabilities of MRI in small animal experiments.

PMID- 21717306
TI  - Detectability of breast lesions under the nipple using an automated breast volume
      scanner: comparison with handheld ultrasonography.
AB  - PURPOSE: The aims of this study were to investigate the visualization rate for
      the mammary gland under the nipple with automated breast ultrasonography (US) and
      to compare the detectability of breast lesions under the nipple with automated
      breast imaging and handheld US imaging. MATERIALS AND METHODS: A total of 60
      patients underwent automated breast US (ABVS; Siemens Medical Solutions, Mountain
      View, CA, USA) and handheld US. The scans of the four segments of the breast
      included sequential scans in the upper-outer (C), lower-outer (D), lower-inner
      (B), and upper-inner (A) regions. RESULTS: The visualization rates for the
      mammary gland under the nipple were 72% (86/120 breasts) in A-scanning, 84%
      (101/120) in B-scanning, 78% (93/120) in C-scanning, and 80% (96/120) in D
      scanning. Interscanning mode differences were statistically significant only for
      A-scanning and B-scanning (P = 0.02). Eventually, 98% (117/120 breasts) of the
      breasts examined were rated as "visualized." In 14 of the 15 patients with breast
      lesions under the nipple, the lesions were detectable with handheld US and the
      ABVS. In the other patient, the lesion was not detectable on handheld US but was
      detected on ABVS imaging. CONCLUSION: ABVS imaging is by no means inferior to
      handheld US for detecting breast lesions under the nipple.

PMID- 21717307
TI  - Signal intensity of lanthanum carbonate on magnetic resonance images: phantom
      study.
AB  - PURPOSE: Lanthanum carbonate (LC) is used to treat hyperphosphatemia. The purpose
      of this study was to investigate the signal intensity (SI) of LC on magnetic
      resonance imaging (MRI) scans of phantoms. MATERIALS AND METHODS: LC tablets were
      thoroughly ground and mixed with distilled water or edible agar (0.05, 0.25, 0.5,
      and 2.5 mg/ml) in plastic bottles. Four intact tablets were placed in plastic
      bottles that did or did not contain distilled water or agar. Two radiologists
      consensually evaluated T1- and T2-weighted images (WIs) obtained with 1.5- and
      3.0-T MRI systems for the SI of unground and ground tablets. RESULTS: On T1- and
      T2WI, the SIs of the LC suspensions and the solvents alone were similar; the SIs
      of unground tablets alone and of the air were also similar. Unground tablets in
      phantoms filled with solvent exhibited lower SI than the solvent. Ground tablets
      in suspension were not visualized on MRI or computed tomography. These results
      remained unchanged regardless of differences in magnetic field strength or the
      solvent used. CONCLUSION: Ground LC had no contrast enhancement effect on T1WI;
      on T2WI it did not affect the SI of the solvent. Unground LC tablets may be
      visualized as a "filling defect" on MRI.

PMID- 21717308
TI  - Functional molecular morphology of anterior pituitary cells, from hormone
      production to intracellular transport and secretion.
AB  - Combined in situ hybridization (ISH) and immunohistochemistry (IHC) under
      electron microscopy (EM-ISH & IHC) has sufficient ultrastructural resolution to
      provide two-dimensional images of subcellular localization of pituitary hormone
      and its mRNA in a pituitary cell. The advantages of semiconductor nanocrystals
      (Quantum dots; Qdots) and confocal laser scanning microscopy (CLSM) enable us to
      obtain three-dimensional images of the subcellular localization of pituitary
      hormone and its mRNA. Both EM-ISH & IHC and ISH & IHC using Qdots and CLSM are
      useful for understanding the relationship between protein and mRNA simultaneously
      in two or three dimensions. CLSM observation of rab3B and SNARE proteins such as
      SNAP-25 and syntaxin revealed that both rab3B and SNARE system proteins play an
      important role and work together as the exocytotic machinery in anterior
      pituitary cells. Another important issue is the intracellular transport and
      secretion of pituitary hormone. An experimental pituitary cell line, the GH3
      cell, in which growth hormone (GH) is linked to enhanced yellow fluorescein
      protein (EYFP), has been developed. This stable GH3 cell secretes GH linked to
      EYFP upon being stimulated by Ca(2+) influx or Ca(2+) release from storage. This
      GH3 cell is useful for real-time visualization of the intracellular transport and
      secretion of GH. These three methods enable us to visualize consecutively the
      processes of transcription, translation, transport, and secretion of pituitary
      hormone.

PMID- 21717309
TI  - Origin of the apical transcytic membrane system in jejunal absorptive cells of
      neonates.
AB  - We investigated the origin of the apical transcytic membrane system in jejunal
      absorptive cells of neonatal rats using light, electron, and immunofluorescence
      microscopy. In rats just after birth, intraluminally injected horseradish
      peroxidase (HRP), used as a macromolecular tracer, was observed only in the
      apical endocytic membrane system including the lysosomes, of jejunal absorptive
      cells in vivo. No tracer, however, was found in the intercellular space between
      the jejunal absorptive cells and the submucosa. Immunoreactive neonatal Fc
      receptor (FcRn) was localized in the perinuclear region of these absorptive cells
      whereas immunoglobulin G (IgG) was not found in these absorptive cells. In
      contrast, in rats 2 h after breast-feeding, intraluminally injected HRP was
      observed in the apical endocytic membrane system and in the apical transcytic
      membrane system of the absorptive cells. Moreover, HRP was found in the
      intercellular space between the jejunal absorptive cells and the submucosa.
      Furthermore, FcRn and IgG were widely distributed throughout the absorptive
      cells, and IgG was detected in both the intercellular space and the submucosa.
      These data suggest that initiation of breast-feeding induces the transportation
      of membrane-incorporated FcRn from its perinuclear localization to the apical
      plasma membrane domain. This transportation is achieved through the membrane
      system, which mediates apical receptor-mediated transcytosis via the trans-Golgi
      network. Subsequently, the apical plasma membrane containing the FcRn binds to
      maternal IgG, is endocytosed into the absorptive cells, and is transported to the
      basolateral membrane domain.

PMID- 21717310
TI  - CD56 expression is associated with neuroectodermal differentiation in
      ameloblastomas: an immunohistochemical evaluation in comparison with odontogenic
      cystic lesions.
AB  - Ameloblastoma (AB), which is the most common odontogenic tumor, may originate
      from the dental lamina remnants. The expression of CD56, which is a transmembrane
      molecule, is associated with neuroectodermal differentiation of the embryonal
      cells. The aim of this study was to evaluate the expression of CD56 in AB, in
      comparison with other odontogenic cysts. We used formalin-fixed, paraffi n
      embedded specimens from 34 cases of AB, 10 cases of keratocystic odontogenic
      tumor (KCOT), and 7 cases of dentigerous cyst (DC). We immunohistochemically
      examined CD56, NeuroD1, and N-cadherin expression in these tumors as compared
      with the expression patterns of various epithelial markers. Seventy-four percent
      of AB showed immunopositivity for CD56, and both CD56 and N-cadherin were
      diffusely positive in the outer columnar cells of AB. The immunopositivities for
      NeuroD1 and N-cadherin were also observed in the outer cells of AB. None of the
      DC cases was positive for CD56, whereas half the cases of KCOT were positive.
      Because CD56 is expressed in the inner enamel epithelium of enamel organs, the
      outer columnar cells of AB are likely to be the differentiation phenotype of the
      inner enamel epithelium, which is associated with neuroectodermal
      differentiation. The aberrant NeuroD1 expression may induce CD56 expression in AB
      and KCOT.

PMID- 21717311
TI  - Accuracy of differential diagnosis for pancreatic cancer is improved in the
      combination of RCAS1 and CEA measurements and cytology in pancreatic juice.
AB  - Improvement of diagnostic accuracy for pancreatic cancer in pancreatic disease
      patients was investigated by examining the combination of three diagnostic
      methods, i.e., measurements of RCAS1 and CEA levels in pancreatic juice and
      pancreatic juice cytology. Pancreatic juice was collected from 12 pancreatic
      cancer (PC) and 26 non-PC patients. RCAS1 and CEA levels were measured by using
      ELISA. RCAS1 expression on surgically resected tissue was immunohistochemically
      examined for 2 PC patients. By setting the cutoff level of RCAS1 at 10 U/ml and
      that of CEA at 18.5 MUg/ml, sensitivity of RCAS1 was 42% and that of CEA was 50%.
      On the other hand, sensitivity and specificity increased from 42% and 85% of
      RCAS1 alone to 75% and 85% in the examination of RCAS1 + CEA + cytology, and the
      false-negative rate was also reduced to 25% in this combination.
      Immunohistochemically, a patient with a high RCAS1 level in pancreatic juice had
      numerous RCAS1-positive tumor cells in the pancreatic juice. We concluded that
      RCAS1 and CEA measurements together with cytology in pancreatic juice would be a
      useful combination method for making a differential diagnosis of PC from non-PC.

PMID- 21717312
TI  - Differential distribution of blood-derived proteins in xenografted human
      adenocarcinoma tissues by in vivo cryotechnique and cryobiopsy.
AB  - Tumor behavior depends on the complex tumor interstitium and microenvironment,
      which influence transport of fluid and soluble molecules from blood vessels. The
      purpose of this study was to reveal how complex tumor tissues affect the
      immunodistribution of serum proteins and time-dependent translocation of bovine
      serum albumin (BSA) from blood vessels, using relatively differentiated human
      adenocarcinoma produced by the xenografted A549 cell line. Histological
      architecture and immunodistribution of the serum proteins in adenocarcinomatous
      tissues were clearly detected by the in vivo cryotechnique and cryobiopsy. Both
      albumin and IgG1 were detected in blood vessels, connective tissues around the
      tumor mass, and the interstitium among tumor cell nests. IgM was mainly detected
      in blood vessels and connective tissues around the tumor mass but was not
      detected in the interstitium among the tumor cell nests. At 10 or 30 min after
      BSA injection, BSA was observed only in blood vessels, but 1 h after the
      injection, it was also detected in the interstitium and surrounding connective
      tissues of the tumor mass. The present findings showed topographic variation of
      molecular permeation in the adenocarcinomatous tumor mass. The interstitial
      tissues with augmented permeability of serum proteins would increase
      accessibility of tumor cells to blood-derived molecules.

PMID- 21717313
TI  - A novel monoclonal antibody identified hepatic stem-like cells in rats.
AB  - Both liver epithelial and oval cells are believed to be liver stem cells. We
      investigated the identification by producing monoclonal antibodies against liver
      epithelial cells. Monoclonal antibodies against hepatic stem-like cells (HSL
      cells) have been selected to follow the hepatic stem cells during hepatic
      regeneration and developmental changes in the liver. Monoclonal antibodies were
      induced by immunization of BALB/c mice with HSL cells established from the
      epithelial cells of the adult rat liver. The hybridomas were screened by indirect
      immunofluorescence staining of HSL cells. We produced a unique monoclonal
      antibody against HSL cells, MabH, which specifically recognizes liver epithelial
      cells. MabH did not react with liver parenchymal cells but did react with bile
      ductule cells under normal conditions in the adult liver. This antibody also
      reacted with oval cell lines and with the oval cells that appeared during liver
      regeneration. In addition, fetal liver cells showed immunoreactivity with MabH.
      Although the level of staining decreased after birth, some cells in the portal
      area remained highly reactive. These results suggested that liver epithelial
      cells, oval cells, and fetal liver cells possess a common cell marker of liver
      stem cells.

PMID- 21717314
TI  - Immunohistochemical application of S100A1 in renal oncocytoma, oncocytic
      papillary renal cell carcinoma, and two variants of chromophobe renal cell
      carcinoma.
AB  - S100A1 is a calcium-binding protein and a member of the S100 family. Recently,
      S100A1 immunohistochemistry may be an available marker in the differential
      diagnosis between renal oncocytoma and chromophobe renal cell carcinoma (RCC).
      However, there are no reports on S100A1 expression in oncocytic papillary RCC
      that has been recently identified. In this article, we immunohistochemically
      examined the expression of S100A1 protein in 18 renal tumors including 4 renal
      oncocytoma, 10 chromophobe RCCs, and 4 oncocytic papillary RCCs. All the cases of
      renal oncocytoma and oncocytic papillary RCC showed a positive reaction for
      S100A1 with cytoplasmic pattern. In chromophobe RCC, 3 of 4 tumors with typical
      variant and 4 of 6 tumors in eosinophilic variant were completely negative for
      S100A1. Finally, S100A1 immunohistochemistry may be useful in distinguishing
      renal oncocytoma from chromophobe RCC, but it may be of no use in the
      differential diagnosis between renal oncocytoma and oncocytic papillary RCC.

PMID- 21717316
TI  - Analyses of bacterial communities in meju, a Korean traditional fermented soybean
      bricks, by cultivation-based and pyrosequencing methods.
AB  - Despite the importance of meju as a raw material used to make Korean soy sauce
      (ganjang) and soybean paste (doenjang), little is known about the bacterial
      diversity of Korean meju. In this study, the bacterial communities in meju were
      examined using both culture-dependent and independent methods in order to
      evaluate the diversity of the bacterial population. Analyses of the 16S rRNA gene
      sequences of the bacterial strains isolated from meju samples showed that the
      dominant species were related to members of the genera Bacillus, Enterococcus,
      and Pediococcus. The community DNAs extracted from nine different meju samples
      were analyzed by barcoded pyrosequencing method targeting of the V1 to V3
      hypervariable regions of the 16S rRNA gene. In total, 132,374 sequences, with an
      average read length of 468 bp, were assigned to several phyla, with Firmicutes
      (93.6%) representing the predominant phylum, followed by Proteobacteria (4.5%)
      and Bacteroidetes (0.8%). Other phyla accounted for less than 1% of the total
      bacterial sequences. Most of the Firmicutes were Bacillus and lactic acid
      bacteria, mainly represented by members of the genera Enterococcus, Lactococcus,
      and Leuconostoc, whose ratio varied among different samples. In conclusion, this
      study indicated that the bacterial communities in meju were very diverse and a
      complex microbial consortium containing various microorganisms got involved in
      meju fermentation than we expected before.

PMID- 21717315
TI  - Transcriptional regulatory elements in fungal secondary metabolism.
AB  - Filamentous fungi produce a variety of secondary metabolites of diverse
      beneficial and detrimental activities to humankind. The genes required for a
      given secondary metabolite are typically arranged in a gene cluster. There is
      considerable evidence that secondary metabolite gene regulation is, in part, by
      transcriptional control through hierarchical levels of transcriptional regulatory
      elements involved in secondary metabolite cluster regulation. Identification of
      elements regulating secondary metabolism could potentially provide a means of
      increasing production of beneficial metabolites, decreasing production of
      detrimental metabolites, aid in the identification of 'silent' natural products
      and also contribute to a broader understanding of molecular mechanisms by which
      secondary metabolites are produced. This review summarizes regulation of
      secondary metabolism associated with transcriptional regulatory elements from a
      broad view as well as the tremendous advances in discovery of cryptic or novel
      secondary metabolites by genomic mining.

PMID- 21717317
TI  - Evaluation of antibacterial activity against Salmonella Enteritidis.
AB  - Salmonella enterica serovar Enteritidis is a well-known pathogenic bacterium
      responsible for human gastrointestinal enteritis mainly due to the consumption of
      eggs and egg-products. The first aim of this work was to study several virulence
      factors of a strain isolated from egg content: SEovo. First, bacterial growth was
      studied at several temperatures and cell morphology was observed by scanning
      electronic microscopy. These experiments showed Salmonella's ability to grow at
      low temperatures and to produce exoproducts. Next, Salmonella motility was
      observed performing swimming, twitching, and swarming tests. Results indicated a
      positive flagellar activity and the cell ability to differentiate and become
      hyperflagellated under specific conditions. Moreover, SEovo adherence and biofilm
      formation was carried out. All of these tests enabled us to conclude that SEovo
      is a potential pathogen, thus it can be used as a model to perform antibacterial
      experiments. The second part of the study was dedicated to the evaluation of the
      antibacterial activity of different molecules using several methods. The
      antibacterial effect of silver and copper aluminosilicates was tested by two
      different kinds of methods. On the one hand, the effect of these two
      antibacterial agents was determined using microbiological methods: viable cell
      count and agar-well diffusion. And on the other hand, the antibacterial activity
      was evaluated using CLSM and SYTO Red/SYTOX Green dyeing. CLSM allowed for the
      evaluation of the biocide on sessile cells, whereas the first methods did not.
      Results showed that adhered bacteria were more resistant than planktonic
      counterparts and that CLSM was a good alternative to evaluate antibacterial
      activity on fixed bacteria without having to carry out a removing step.

PMID- 21717319
TI  - Molecular analysis of a prolonged spread of Klebsiella pneumoniae co-producing
      DHA-1 and SHV-12 beta-lactamases.
AB  - The study investigated molecular mechanisms for prolonged nosocomial spread of
      multidrug-resistant Klebsiella pneumoniae co-producing plasmid-mediated AmpC beta
      lactamase DHA-1 and extended-spectrum beta-lactamase SHV-12. Forty-eight clinical
      isolates of K. pneumonia, resistant to the extended-spectrum cepha-losporins,
      were collected in a 750-bed university hospital over a year. The isolates were
      characterized for PCR-based beta-lactamase genotypes, isoelectric focusing and
      pulsed-field gel electrophoresis (PFGE) profiles. Resistance transfer was
      performed by plasmid conjugation and confirmed by a duplex-PCR and Southern
      hybridization. On beta-lactamase typing, the strains producing only the DHA-1
      enzyme (n=17) or co-producing DHA-1 and SHV-12 enzymes (n=15) were predominant.
      Judging from a one year-distribution of PFGE profiles, the co-producer was spread
      primarily with single clonal expansion of the PFGE-type A with subtypes (n=14),
      whereas the strains producing only DHA-1 enzyme were spread simultaneously with
      the PFGE-type A (n=ll) and other PFGE types (n=6). Transconjugants of the co
      producers were confirmed to harbor either both bla (DHA-1) and bla (SHV-12) or
      only the bla (DHA-1). In conclusion, this study indicated that the persistent
      nosocomial spread of multidrug-resistant K. pneumoniae strains was primarily
      associated with expansion of a clone harboring both the bla (DHA-1) and bla (SHV
      12) or the bla (DHA-1) only, and to a lesser extent with the horizontal transfer
      of the resistant plasmids. Our observations have clinical implication for the
      control and prevention of nosocomial dissemination of multidrug-resistant K.
      pneumoniae strains.

PMID- 21717320
TI  - The impacts of excessive nitrogen additions on enzyme activities and nutrient
      leaching in two contrasting forest soils.
AB  - Nitrogen (N) deposition has increased dramatically worldwide, which may affect
      forest soils in various ways. In this study, we conducted a short-term
      manipulation experiment of N addition on two types of forest soils (urban and
      rural soils) found in Korea. N addition significantly decreased phenol oxidase
      activities in urban soil samples; however, it did not affect those in rural
      soils. Furthermore, N addition did not change beta-glucosidase and N
      acetylglucosaminidase activities, except for beta-glucosidase activities in the O
      layer of rural soils. Changes in microbial biomass and general activity
      (dehydrogenase activity) were not induced by N addition, except for dehydrogenase
      in the A layer of urban soils. Although N addition did not change the extractable
      soil nutrients, organic matter, and water contents significantly, it enhanced
      nutrient leaching and resulted in lower pH leachate. These results suggest that
      excessive N addition to forest soils may induce nutrient leaching in the long
      term. Overall results of our study also suggest that N addition may induce
      retardation of organic matter decomposition in soils; however, such a response
      may depend on the intensity of previous exposure to N deposition.

PMID- 21717321
TI  - Biochemical analysis of a fibrinolytic enzyme purified from Bacillus subtilis
      strain A1.
AB  - A fibrinolytic enzyme from Bacillus subtilis strain Al was purified by
      chromatographic methods, including DEAE Sephadex A-50 column chromatography and
      Sephadex G-50 column gel filtration. The purified enzyme consisted of a monomeric
      subunit and was estimated to be approximately 28 kDa in size by SDS-PAGE. The
      specific activity of the fibrinolytic enzyme was 1632-fold higher than that of
      the crude enzyme extract. The fibrinolytic activity of the purified enzyme was
      approximately 0.62 and 1.33 U/ml in plasminogen-free and plasminogen-rich fibrin
      plates, respectively. Protease inhibitors PMSF, DIFP, chymostatin, and TPCK
      reduced the fibrinolytic activity of the enzyme to 13.7, 35.7, 15.7, and 23.3%,
      respectively. This result suggests that the enzyme purified from B. subtilis
      strain Al was a chymotrypsin-like serine protease. In addition, the optimum
      temperature and pH range of the fibrinolytic enzyme were 50 degrees C and 6.0
      10.0, respectively. The N-terminal amino acid sequence of the purified enzyme was
      identified as Q-T-G-G-S-I-I-D-P-I-N-G-Y-N, which was highly distinguished from
      other known fibrinolytic enzymes. Thus, these results suggest a fibrinolytic
      enzyme as a novel thrombolytic agent from B. subtilis strain Al.

PMID- 21717318
TI  - Cultured bacterial diversity and human impact on alpine glacier cryoconite.
AB  - The anthropogenic effect on the microbial communities in alpine glacier
      cryoconites was investigated by cultivation and physiological characterization of
      bacteria from six cryoconite samples taken at sites with different amounts of
      human impact. Two hundred and forty seven bacterial isolates were included in
      Actinobacteria (9%, particularly Arthrobacter), Bacteroidetes (14%, particularly
      Olleya), Firmicutes (0.8%), Alphaproteobacteria (2%), Betaproteobacteria (16%,
      particularly Janthinobacterium), and Gammaproteobacteria (59%, particularly
      Pseudomonas). Among them, isolates of Arthrobacter were detected only in samples
      from sites with no human impact, while isolates affiliated with
      Enterobacteriaceae were detected only in samples from sites with strong human
      impact. Bacterial isolates included in Actinobacteria and Bacteroidetes were
      frequently isolated from pristine sites and showed low maximum growth temperature
      and enzyme secretion. Bacterial isolates included in Gammaproteobacteria were
      more frequently isolated from sites with stronger human impact and showed high
      maximum growth temperature and enzyme secretion. Ecotypic differences were not
      evident among isolates of Janthinobacterium lividum, Pseudomonas fluorescens, and
      Pseudomonas veronii, which were frequently isolated from sites with different
      degrees of anthropogenic effect.

PMID- 21717322
TI  - Shewanella upenei sp. nov., a lipolytic bacterium isolated from bensasi goatfish
      Upeneus bensasi.
AB  - A Gram-staining-negative, motile, non-spore-forming and rod-shaped bacterial
      strain, 20-23R(T), was isolated from intestine of bensasi goatfish, Upeneus
      bensasi, and its taxonomic position was investigated by using a polyphasic study.
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain 20
      23R(T) belonged to the genus Shewanella. Strain 20-23R(T) exhibited 16S rRNA gene
      sequence similarity values of 99.5, 99.2, and 97.5% to Shewanella algae ATCC
      51192(T), Shewanella haliotis DW01(T), and Shewanella chilikensis JC5(T),
      respectively. Strain 20-23R(T) exhibited 93.1-96.0% 16S rRNA gene sequence
      similarity to the other Shewanella species. It also exhibited 98.3-98.4% gyrB
      sequence similarity to the type strains of S. algae and S. haliotis. Strain 20
      23R(T) contained simultaneously both menaquinones and ubiquinones; the
      predominant menaquinone was MK-7 and the predominant ubiquinones were Q-8 and Q
      7. The fatty acid profiles of strain 20-23R(T), S. algae KCTC 22552(T) and S.
      haliotis KCTC 12896(T) were similar; major components were iso-C(15:0), C(16:0),
      C(16:1) omega7c and/or iso-C(15:0) 2-OH and C(17:1) omega8c. The DNA G+C content
      of strain 20-23R(T) was 53.9 mol%. Differential phenotypic properties and genetic
      distinctiveness of strain 20-23R(T), together with the phylogenetic
      distinctiveness, revealed that this strain is distinguishable from recognized
      Shewanella species. On the basis of the data presented, strain 20-23R(T)
      represents a novel species of the genus Shewanella, for which the name Shewanella
      upenei sp. nov. is proposed. The type strain is 20-23R(T) (=KCTC 22806(T) =CCUG
      58400(T)).

PMID- 21717323
TI  - Flavobacterium koreense sp. nov., Flavobacterium chungnamense sp. nov., and
      Flavobacterium cheonanense sp. nov., isolated from a freshwater reservoir.
AB  - Taxonomic studies were performed on three strains isolated from Cheonho reservoir
      in Cheonan, Korea. The isolates were Gram-negative, aerobic, rod-shaped, non
      motile, catalase-positive, and oxidase-positive. Colonies on solid media were
      cream-yellow, smooth, shiny, and circular. Phylogenetic analysis of the 16S rRNA
      gene sequences revealed that these strains belong to the genus Flavobacterium.
      The strains shared 98.6-99.4% sequence similarity with each other and showed less
      than 97% similarity with members of the genus Flavobacterium with validly
      published names. The DNA-DNA hybridization results confirmed the separate genomic
      status of strains ARSA-42(T), ARSA-103(T), and ARSA-108(T). The isolates
      contained menaqui-none-6 as the predominant menaquinone and iso-C(15:0), iso
      C(15:0) 3-OH, iso-Ci(15:1) G, and iso-C(16:0) 3-OH as the major fatty acids. The
      genomic DNA G+C content of the isolates were 31.4-33.2 mol%. According to the
      phenotypic and genotypic data, these organisms are classified as representative
      of three novel species in the genus Flavobacterium, and the name Flavobacterium
      koreense sp. nov. (strain ARSA-42(T) =KCTC 23182(T) =JCM 17066(T) =KACC
      14969(T)), Flavobacterium chungnamense sp. nov. (strain ARSA-103(T) =KCTC
      23183(T) =JCM 17068(T) =KACC 14971(T)), and Flavobacterium cheonanense sp. nov.
      (strain ARSA-108(T) =KCTC 23184(T) =JCM 17069(T) =KACC 14972) are proposed.

PMID- 21717324
TI  - Mucilaginibacter composti sp. nov., with ginsenoside converting activity,
      isolated from compost.
AB  - The Gram-negative, strictly aerobic, non-motile, non-spore-forming, rod shaped
      bacterial strain designated TR6-03(T) was isolated from compost, and its
      taxonomic position was investigated by using a polyphasic approach. Strain TR6
      03(T) grew at 4-42 degrees C and at pH 6.0-8.0 on R2A and nutrient agar without
      NaCl supplement. Strain TR6-03(T) had beta-glucosidase activity, which was
      responsible for its ability to transform ginsenoside Re (one of the dominant
      active components of ginseng) to Rg(2). On the basis of 16S rRNA gene sequence
      similarity, strain TR6-03(T) was shown to belong to the family
      Sphingobacteriaceae and to be related to Mucilaginibacter lappiensis ANJLI2(T)
      (96.3% sequence similarity), M. dorajii FR-f4(T) (96.1%), and M. rigui WPCB133(T)
      (94.1%). The G+C content of the genomic DNA was 45.6%. The predominant
      respiratory quinone was MK-7 and the major fatty acids were summed feature 3
      (comprising C(16:1) omega7c and/or iso-C(15:0) 20H), iso-C(16:0) and iso-C(17:0)
      3OH. DNA and chemotaxonomic data supported the affiliation of strain TR6-03(T) to
      the genus Mucilaginibacter. Strain TR6-03(T) could be differentiated
      genotypically and phenotypically from the recognized species of the genus
      Mucilaginibacter. The isolate therefore represents a novel species, for which the
      name Mucilaginibacter composti sp. nov. is proposed, with the type strain TR6
      03(T) (=KACC 14956(T) = KCTC 12642(T) =LMG 23497(T)).

PMID- 21717325
TI  - Molecular cloning, purification, and characterization of a superoxide dismutase
      from a fast-growing Mycobacterium sp. Strain JC1 DSM 3803.
AB  - A cytosolic superoxide dismutase (SOD) was purified and characterized from a fast
      growing Mycobacterium sp. strain JC1 DSM 3803 grown on methanol. The native
      molecular weight of the purified SOD was estimated to be 48 kDa. SDS-PAGE
      revealed a subunit of 23 kDa, indicating that the enzyme is a homodimer. The
      enzyme activity was inhibited by H(2)O(2) and azide. The purified SOD contained
      1.12 and 0.56 g-atom of Mn and Fe per mol of enzyme, respectively, suggesting
      that it may be a Fe/Mn cambialistic SOD. The apo-SOD reconstitution study
      revealed that Mn salts were more specific than Fe salts in the SOD activity. The
      gene encoding the SOD was identified from the JC1 cosmid genomic library by PCR
      screening protocol. The cloned gene, sodA, had an open reading frame (ORF) of 624
      nt, encoding a protein with a calculated molecular weight of 22,930 Da and pi of
      5.33. The deduced SodA sequence exhibited 97.6% identity with that of
      Mycobacterium fortuitum Mn-SOD and clustered with other mycobacterial Mn-SODs. A
      webtool analysis on the basis of SOD sequence and structure homologies predicted
      the SOD as a tetrameric Mn-SOD, suggesting that the protein is a dimeric Mn-SOD
      having tetramer-specific sequence and structure characteristics.

PMID- 21717326
TI  - Biochemical characteristization of propionyl-coenzyme a carboxylase complex of
      Streptomyces toxytricini.
AB  - Acyl-CoA carboxylases (ACC) are involved in important primary or secondary
      metabolic pathways such as fatty acid and/or polyketides synthesis. In the 62 kb
      fragment of pccB gene locus of Streptomyces toxytricini producing a pancreatic
      inhibitor lipstatin, 3 distinct subunit genes of presumable propionyl-CoA
      carboxylase (PCCase) complex, assumed to be one of ACC responsible for the
      secondary metabolism, were identified along with gene for a biotin protein ligase
      (Bpl). The subunits of PCCase complex were a subunit (AccA3), P subunit (PccB),
      and auxiliary E subunit (PccE). In order to disclose the involvement of the
      PCCase complex in secondary metabolism, some biochemical characteristics of each
      subunit as well as their complex were examined. In the test of substrate
      specificity of the PCCase complex, it was confirmed that this complex showed much
      higher conversion of propionyl-CoA rather than acetyl-CoA. It implies the enzyme
      complex could play a main role in the production of methylmalonyl-CoA from
      propionyl-CoA, which is a precursor of secondary polyketide biosynthesis.

PMID- 21717327
TI  - Genotypic and phenotypic characteristics of tunisian isoniazid-resistant
      Mycobacterium tuberculosis strains.
AB  - Forty three isoniazid (INH)-resistant Mycobacterium tuberculosis isolates were
      characterized on the basis of the most common INH associated mutations, katG315
      and mabA -15C->T, and phenotypic properties (i.e. MIC of INH, resistance
      associated pattern, and catalase activity). Typing for resistance mutations was
      performed by Multiplex Allele-Specific PCR and sequencing reaction. Mutations at
      either codon were detected in 67.5% of isolates: katG315 in 37.2, mabA -15C->T in
      27.9 and both of them in 2.4%, respectively. katG sequencing showed a G insertion
      at codon 325 detected in 2 strains and leading to amino acid change T326D which
      has not been previously reported. Distribution of each mutation, among the
      investigated strains, showed that katG S315T was associated with multiple-drug
      profile, high-level INH resistance and loss or decreased catalase activity;
      whereas the mabA -15C->T was more prevalent in mono-INH resistant isolates, but
      it was not only associated with a low-level INH resistance. It seems that
      determination of catalase activity aids in the detection of isolates for which
      MICs are high and could, in conjunction with molecular methods, provide rapid
      detection of most clinical INH-resistant strains.

PMID- 21717328
TI  - The MpkB MAP kinase plays a role in post-karyogamy processes as well as in hyphal
      anastomosis during sexual development in Aspergillus nidulans.
AB  - Two genes encoding MAP kinase homologs, designated as mpkB and mpkC, were
      isolated from Aspergillus nidulans by PCR with degenerate primers. Deletion and
      over-expression mutants of mpkC showed no detectable phenotypes under any
      external stress tested. Deletion of mpkB caused pleiotropic phenotypes including
      a failure in forming cleistothecia under any induction conditions for sexual
      development, increased Hulle cell production, slow hyphal growth and aberrant
      conidiophore morphology. Over-expression of mpkB led to increased cleistothecium
      production. While the transcripts of mpkB and mpkC were constitutively
      synthesized through the entire life cycle, their size and amount differed with
      developmental stages. An outcross test using fluorescent protein reporters showed
      that the mpkB deletion mutant could not form heterokaryons with wild type.
      Protoplast fusion experiments showed that the fusant of the mpkB mutant with wild
      type could undergo normal sexual development. However, heterokaryotic mycelia
      that were produced from a fusant between two mpkB deletion mutants could not form
      cleistothecia, although they did appear to form diploid nuclei. These results
      suggest that the MpkB MAP kinase is required for some post-karyogamy process as
      well as at the hyphal anastomosis stage to accomplish sexual development
      successfully.

PMID- 21717329
TI  - Identification of the genes involved in 1-deoxynojirimycin synthesis in Bacillus
      subtilis MORI 3K-85.
AB  - 1-Deoxynojirimycin (DNJ), a D-glucose analogue with a nitrogen atom substituting
      for the ring oxygen, is a strong inhibitor of intestinal alpha-glucosidase. DNJ
      has several promising biological activities, including its antidiabetic,
      antitumor, and antiviral activities. Nevertheless, only limited amounts of DNJ
      are available because it can only be extracted from some higher plants, including
      the mulberry tree, or purified from the culture broth of several types of soil
      bacteria, such as Streptomyces sp. and Bacillus sp. In our previous study, a DNJ
      producing bacterium, Bacillus subtilis MORI, was isolated from the traditional
      Korean fermented food Chungkookjang. In the present study, we report the
      identification of the DNJ biosynthetic genes in B. subtilis MORI 3K-85 strain, a
      DNJ-overproducing derivate of the B. subtilis MORI strain generated by gamma
      irradiation, xhe genomic DNA library of B. subtilis MORI 3K-85 was constructed in
      Escherichia coli, and clones showing alpha-glucosidase inhibition activity were
      selected. After DNA sequencing and a series of subcloning, we were able to
      identify a putative Operon which consists of gabT1, yktc1, and gutB1 genes
      predicted to encode putative transaminase, phosphatase, and oxidoreductase,
      respectively. When a recombinant plasmid containing this Operon sequence was
      transformed into an E. coli strain, the resulting transformant was able to
      produce DNJ into the culture medium. Our results indicate that the gabT1, yktc1,
      and gutB1 genes are involved in the DNJ biosynthetic pathway in B. subtilis MORI,
      suggesting the possibility of employing these genes to establish a large-scale
      microbial DNJ overproduction system through genetic engineering and process
      optimization.

PMID- 21717330
TI  - Sulfolipid accumulation in Mycobacterium tuberculosis disrupted in the mce2
      operon.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis, has a lipid-rich
      cell wall that serves as an effective barrier against drugs and toxic host cell
      products, which may contribute to the organism's persistence in a host. M.
      tuberculosis contains four homologous operons called nice (mce1-4) that encode
      putative ABC transporters involved in lipid importation across the cell wall.
      Here, we analyzed the lipid composition of M. tuberculosis disrupted in the mce2
      operon. High resolution mass spectrometric and thin layer chromatographic
      analyses of the mutant's cell wall lipid extracts showed accumulation of SL-1 and
      SL(1278) molecules. Radiographic quantitative analysis and densitometry revealed
      2.9, 3.9 and 9.8-fold greater amount of [(35)S] SL-1 in the mce2 operon mutant
      compared to the wild type M. tuberculosis during the early/mid logarithmic, late
      logarithmic and stationary phase of growth in liquid broth, respectively. The
      amount of [(35)S] SL(1278) in the mutant also increased progressively over the
      same growth phases. The expression of the mce2 operon genes in the wild type
      strain progressively increased from the logarithmic to the stationary phase of
      bacterial growth in vitro, which inversely correlated with the proportion of
      radiolabel incorporation into SL-1 and SL(1278) at these phases. Since the mce2
      operon is regulated in wild type M. tuberculosis, its cell wall may undergo
      changes in SL-1 and SL(1278) contents during a natural course of infection and
      this may serve as an important adaptive strategy for M. tuberculosis to maintain
      persistence in a host.

PMID- 21717331
TI  - Epidemiological features and resistance pattern in uropathogens isolated from
      chronic bacterial prostatitis.
AB  - Chronic bacterial prostatitis (CBP) is, usually, caused by uropathogens,
      especially gram-negative bacilli, although infection is sometimes due to Gram
      positive and atypical microorganisms. A recent increasing in prevalence of Gram
      positive strains has been reported. The aim of this study was to explore the
      epidemiological features and resistance rates in uropathogens isolated from CBP
      outpatients in last 10 years. All consecutive outpatients with demonstrated CBP
      attending a single Sexually Transmitted Disease centre from January 1997 and
      December 2008, were enrolled and underwent microbiological cultures in first void
      early morning urine, midstream urine, expressed prostatic secretion, and post
      prostate massage urine. Prevalence of different bacterial strains was stratified
      in four different periods: 1997-1999, 2000-2002, 2003-2005, 2006-2008. Any
      changes observed in epidemiological features and resistance rates in uropathogens
      over the whole study period have been analyzed. The present study has been
      planned, thus, as in vitro study. From 6,221 patients, 4,601 Gram-positive and
      1,620 Gram-negative bacterial strains have been isolated. Enterococcus faecalis
      and Escherichia coli strains are the first and second frequent pathogens found,
      respectively. Significant differences between E. faecalis prevalence in the 1997
      1999 and 2006-2008 periods were found. E. coli showed a significant difference
      between prevalence in 1997-1999 and 2006-2008 periods. Gram-positive organisms
      showed a decreasing of susceptibility to ciprofloxacin as well as Gram-negative
      strains, while a good susceptibility to the levofloxacin was evidenced. E.
      faecalis prevalence seemed to be raised in 2006-2008 periods. Moreover, a
      decreasing of activity of ciprofloxacin and a good activity profile of
      levofloxacin have been reported.

PMID- 21717332
TI  - Purification and partial characterization of a detergent and oxidizing agent
      stable alkaline protease from a newly isolated Bacillus subtilis VSG-4 of
      tropical soil.
AB  - An extracellular detergent tolerant protease producing strain VSG-4 was isolated
      from tropical soil sample and identified as Bacillus subtilis based on
      morphological, biochemical characteristics as well as 16S-rRNA gene sequencing.
      The VSG-4 protease was purified to homogeneity using ammonium sulphate
      precipitation, dialysis and sephadex G-200 gel permeation chromatography with a
      17.4 purification fold. The purified enzyme was active and stable over a broad
      range of pH (8.0-11.0, optimum at 9.0) and temperature (40 degrees C to 60
      degrees C, optimum at 50 degrees C). The thermostability of the enzyme was
      significantly increased by the addition CaCl(2). This enzyme was strongly
      inhibited by PMSF and DFP, suggesting that it belongs to the serine protease
      superfamily. The purified VSG-4 alkaline protease showed remarkable stability in
      anionic (5 mM SDS) and ionic (1% Trion X-100 and 1% Tween 80) detergents. It
      retained 97+/-2% and 83.6+/-1.1% of its initial activity after 1 h preincubation
      in the presence of 1 % H(2)O(2) and 1 % sodium perborate, respectively.
      Furthermore, the purified enzyme showed excellent stability and compatibility
      with some commercial laundry detergents besides its stain removal capacity.
      Considering these promising properties, VSG-4 protease may find tremendous
      application in laundry detergent formulations.

PMID- 21717333
TI  - Predicting genetic traits and epitope analysis of apxIVA in Actinobacillus
      pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae causes a severe hemorrhagic pneumonia in pigs.
      Fifteen serotypes of A. pleuropneumoniae express four different Apx toxins that
      belong to the pore-forming repeats-in-toxin (RTX) group of toxins. ApxIV, which
      is conserved and up-regulated in vivo, could be an excellent candidate for the
      development of a protective cross-serotype immunity vaccine, and could aid in the
      differential diagnosis of diseases caused by A. pleuropneumoniae. We identified
      and sequenced apxIVA from A. pleuropneumoniae serotype 2 isolated in Korea (Kor
      ApxIVA). The Kor-ApxIVA was closely related to Switzerland (AF021919), China
      (CP000687), and China (GQ332268), showing 98.6%, 98.4%, and 97.2% amino acid
      homology, respectively. The level of amino acid homology, however, was higher
      than the nucleotide homology. The structural characteristics of ApxIVA showed RTX
      proteins, including N-terminal hydrophobic domains, signature sequences for
      potential acylation sites, and repeated glycine-rich nonapeptides in the C
      terminal region of the protein. Thirty glycine-rich nonapeptides with the
      consensus sequence, L/V-X-G-G-X-G-N/D-D-X, were found in the C-terminus of the
      Kor-ApxIVA. In addition, the Kor-ApxIVA was predicted for the linear B-cell
      epitopes and conserved domains with determined peptide sequences. This genetic
      analysis of the Kor-ApxIVA might be an important foundation for future biological
      and functional research on ApxIVA.

PMID- 21717334
TI  - High efficiency transformation by electroporation of Yarrowia lipolytica.
AB  - Yarrowia lipolytica was usually transformed by heat shock, but linearized
      integrative vectors always resulted in a low transformation efficiency when
      electroporation was used. To develop a high efficiency integrative transformation
      method by electroporation of F. lipolytica, we report here that pretreatment of
      F. lipolytica with 150 mM LiAc for 1 h before electroporation will approximately
      30-fold of increase transformation efficiency. A cell concentration of 10(10)/ml
      and instrument settings of 1.5 kV will generate the highest transformation
      efficiencies. We have developed a procedure to transform F. lipolytica that will
      be able to yield an efficiency of 2.1 * 10(4) transformants/ug for integrative
      linear DNA. With our modifications, the electroporation procedures became a very
      efficient and reliable tool for F. lipolytica transformation.

PMID- 21717335
TI  - Isolation and characterization of a reducing polyketide synthase gene from the
      lichen-forming fungus Usnea longissima.
AB  - The reducing polyketide synthases found in filamentous fungi are involved in the
      biosynthesis of many drugs and toxins. Lichens produce bioactive polyketides, but
      the roles of reducing polyketide synthases in lichens remain to be clearly
      elucidated. In this study, a reducing polyketide synthase gene (U1PKS3) was
      isolated and characterized from a cultured mycobiont of Usnea longissima.
      Complete sequence information regarding U1PKS3 (6,519 bp) was obtained by
      screening a fosmid genomic library. A U1PKS3 sequence analysis suggested that it
      contains features of a reducing fungal type I polyketide synthase with beta
      ketoacyl synthase (KS), acyltransferase (AT), dehydratase (DH), enoyl reductase
      (ER), ketoacyl reducatse (KR), and acyl carrier protein (ACP) domains. This
      domain structure was similar to the structure of ccRadsl, which is known to be
      involved in resorcylic acid lactone biosynthesis in Chaetomium chiversii. The
      results of phylogenetic analysis located U1PKS3 in the clade of reducing
      polyketide synthases. RT-PCR analysis results demonstrated that UIPKS3 had six
      intervening introns and that UIPKS3 expression was upregulated by glucose,
      sorbitol, inositol, and mannitol.

PMID- 21717336
TI  - Complementation system for Helicobacter pylori.
AB  - Previously Langford et al. (2006) developed the pIR203C04 complementation system
      for Helicobacter pylori, which can be used to complement and restore phenotypic
      effects in H. pylori mutant, and furthermore they used the complementation system
      in vivo experiments to animals without altering the ability of strain SSI to
      colonize mice. In their previous study, the pIR203C04 was able to transform
      26695, SSI, J99, and 43504 H. pylori strains by an electroporation method.
      However, in the present study using a natural transformation the pIR203C04
      transformed only 26695 H. pylori but not SSI, J99, 7.13, and G27 H. pylori
      strains. Since the useful complementation system has a limitation of narrow
      selection among H. pylori strains, we redesigned the complementation system for
      the improvement. The same intergenic chromosomal site between hp0203 and hp0204
      was utilized for the new complementation system because the insertion at the
      intergenic site didn't show any polar effects and disruption of other H. pylori
      genes. The genome sequence analysis showed that the intergenic regions among H.
      pylori strains may have too low homology to each others to do a homologous
      recombination. Thus, in addition to the short intergenic region, the fragments of
      the new complementation system included 3' conserved parts of hp0203 and hp0204
      coding regions. Between the fragments there are a chloramphenicol
      acetyltransferase cassette and multicloning sites, resulting in pKJMSH. DNA
      fragment of the interest can be cloned into the multicloning sites of pKJMSH and
      the fragment can be integrated at the intergenic region of H. pylori chromosome
      by the homologous recombination. Indeed, by the natural transformation, pKJMSH
      was able to transform all five H. pylori strains of 26695, SSI, J99, 7.13, and
      G27, which are common for the investigation of molecular pathogenesis. Thus, the
      new pKJMSH complementation system is applicable to most H. pylori wild-type
      stains.

PMID- 21717337
TI  - Ruminococcus faecis sp. nov., isolated from human faeces.
AB  - Bacterial strain Eg2(T), an anaerobic, Gram-positive, non-motile, and non-spore
      forming coccus, was isolated from human faeces. The optimal temperature for its
      growth was 37 degrees C. Oxidase activity was negative, but catalase activity was
      positive. The strain was able to hydrolyze esculin and to produce acids from the
      fermentation of several substrates, including glucose. Lactic and acetic acids
      were the main products of glucose fermentation. The major fatty acids present in
      this strain were C(16:0), C(14:0), and C(18:1) cis11 DMA. The G+C content was
      43.4 mol%. Based on the 16S rRNA gene sequence, strain Eg2(T) was closely related
      to species of the genus Ruminococcus (96.3% similarity to R. torques and 96.2%
      similarity to R. lactaris), and its taxonomic position was placed within the
      Clostridium cluster XIVa. Based on phenotypic, chemotaxonomic, genotypic, and
      phylogenetic evidence, we propose that this novel strain be assigned to the genus
      Ruminococcus and be named Ruminococcus faecis sp. nov. The type strain is Eg2(T)
      (=KCTC 5757(T) =JCM 15917(T)).

PMID- 21717338
TI  - Diversity of bovine rumen methanogens In vitro in the presence of condensed
      tannins, as determined by sequence analysis of 16S rRNA gene library.
AB  - Molecular diversity of rumen archaeal populations from bovine rumen fluid
      incubated with or without condensed tannins was investigated using 16S rRNA gene
      libraries. The predominant order of rumen archaea in the 16S rRNA gene libraries
      of the control and condensed tannins treatment was found to belong to a novel
      group of rumen archaea that is distantly related to the order Thermoplasmatales,
      with 59.5% (15 phylotypes) and 81.43% (21 phylotypes) of the total clones from
      the control and treatment clone libraries, respectively. The 16S rRNA gene
      library of the control was found to have higher proportions of methanogens from
      the orders Methanomicrobiales (32%) and Methanobacteriales (8.5%) as compared to
      those found in the condensed tannins treatment clone library in both orders
      (16.88% and 1.68% respectively). The phylotype distributed in the order
      Methanosarcinales was only found in the control clone library. The study
      indicated that condensed tannins could alter the diversity of bovine rumen
      methanogens.

PMID- 21717339
TI  - A modified immunoblot method to identify substrates of protein kinases.
AB  - While protein kinases are key components in multiple cellular processes,
      efficient identification of cognate in vivo substrates remains challenging. Here
      we describe a powerful method to screen potential substrates of protein kinases
      by partial transfer of proteins from a 2D-PAGE gel to a Western blot membrane.
      This approach allowed precise pinpointing of candidate substrate spots in the 2D
      gel, and identifying physiological substrates of protein kinases in Mycobacterium
      tuberculosis.

PMID- 21717340
TI  - Paralcaligenes ureilyticus gen. nov., sp. nov. isolated from soil of a Korean
      ginseng field.
AB  - A bacterial strain, designated GR24-5(T), was isolated from soil cultivated with
      Korean ginseng. Cells were Gram-negative, strictly aerobic, catalase- and oxidase
      positive, non-spore-forming motile rods. Based on the 16S rRNA gene sequence,
      strain GR24-5(T) could be assigned to the family Alcaligenaceae. Strain GR24-5(T)
      showed the highest sequence similarities with Parapusillimonas granuli Ch07(T)
      (97.1%), Pusillimonas noertemannii BN9(T) (96.9%), Pigmentiphaga kullae DSM
      13608(T) (96.5%), and Castellaniella defragrans 54Pin(T) (96.3%). Strain GR24
      5(T) demonstrated a low DNA-DNA relatedness (23%) with P. granuli Ch07(T). The
      major respiratory quinone is ubiquinone 8 (Q-8) and the major fatty acids are
      C(16:0), C(17:0) cyclo, and summed feature 1 (C(14:0) 3-OH/iso-C(16:1) I/C(12:0)
      aide). Putrescine, spermidine, and 2-hydroxyputrescine are the major polyamines.
      The major polar lipids are phosphatidylmethylethanolamine,
      phosphatidylethanolamine, phosphatidylglycerol, di-phosphatidylglycerol, and an
      unknown aminophospholipid. Polar lipid patterns of strain GR24-5(T) were unique
      in having a large amount of phosphatidylmethylethanolamine. Based on phylogenetic
      analysis and physiological and biochemical characteristics, strain GR245(T)
      represents a novel genus and species, for which the name Paralcaligenes
      ureilyticus gen. nov., sp. nov. is proposed. The type strain of P. aralcaligenes
      ureilyticus is GR24-5(T) (=KACC 13888 =DSM 24591(T)).

PMID- 21717341
TI  - RNase G participates in processing of the 5'-end of 23S ribosomal RNA.
AB  - In Escherichia coli, primary rRNA transcripts must be processed by a complex
      process in which several ribonucleases are involved in order to generate mature
      16S, 23S, and 5S rRNA molecules. While it is known that RNase G, a single
      stranded RNA-specific endoribonuclease encoded by the rng gene, plays an active
      role in the maturation of the 5'-end of 16S rRNA, its involvement in the
      maturation of the 5'-end of 23S rRNA remains unclear. Here we show that E. coli
      cells deleted for the rng gene accumulate the 23S rRNA precursor containing an
      extra 77 nucleotides at its mature 5'-end. In vitro cleavage assays show that
      RNase G cleaves synthetic RNA containing a sequence encompassing the 5'-end to 77
      nucleotides upstream of mature 23S rRNA at two sites present in single-stranded
      regions. Our results suggest the involvement of RNase G in the processing of the
      5'-region of 23S rRNA precursors.

PMID- 21717342
TI  - Providencia isolates carrying bla (PER-1) and bla (VIM-2) genes: biofilm-forming
      capacity and biofilm inhibitory concentrations for carbapenem antibiotics.
AB  - Multidrug-resistant clinical isolates of Providentia carrying bla (PER-1) and bla
      (VIM-2) were evaluated for the abilities to form biofilm and high biofilm forming
      capacity was demonstrated in them. Minimum biofilm inhibitory concentrations
      (MBICs), minimum biofilm eradication concentrations (MBECs), and minimum
      inhibitory concentrations (MICs) for imipenem and meropenem were also determined.
      In all tested strains, the MBICs were higher than the MICs for both drugs.
      Interestingly, the MBICs and the MBEC(50) for meropenem were lower than those for
      imipenem in the isolates producing high amounts of biofilm, suggesting that
      meropenem is superior to imipenem in the growth inhibition and eradication of
      biofilm forming Providentia strains.

PMID- 21717344
TI  - Fungal prions: structure, function and propagation.
AB  - Prions are not uniquely associated with rare fatal neurodegenerative diseases in
      the animal kingdom; prions are also found in fungi and in particular the yeast
      Saccharomyces cerevisiae. As with animal prions, fungal prions are proteins able
      to exist in one or more self-propagating alternative conformations, but show
      little primary sequence relationship with the mammalian prion protein PrP.
      Rather, fungal prions represent a relatively diverse collection of proteins that
      participate in key cellular processes such as transcription and translation. Upon
      switching to their prion form, these proteins can generate stable, sometimes
      beneficial, changes in the host cell phenotype. Much has already been learnt
      about prion structure, and propagation and de novo generation of the prion state
      through studies in yeast and these findings are reviewed here.

PMID- 21717343
TI  - Packaging of porcine reproductive and respiratory syndrome virus replicon RNA by
      a stable cell line expressing its nucleocapsid protein.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the
      Arteriviridae family, is one of the most common and economically important swine
      pathogens. Although both live-attenuated and killed-inactivated vaccines against
      the virus have been available for a decade, PRRSV is still a major problem in the
      swine industry worldwide. To explore the possibility of producing single-round
      infectious PRRSV replicon particles as a potential vaccine strategy, we have now
      generated two necessary components: 1) a stable cell line (BHK/Sinrepl9/PRRSV-N)
      that constitutively expresses the viral nucleocapsid (N) protein localized to the
      cytoplasm and the nucleolus and 2) a PRRSV replicon vector (pBAC/PRRSV/Replicon
      AN) with a 177-nucleotide deletion, removing the 3'-half portion of ORF7 in the
      viral genome, from which the self-replicating propagation-defective replicon RNAs
      were synthesized in vitro by SP6 polymerase run-off transcription. Transfection
      of this replicon RNA into N protein-expressing BHK-21 cells led to the secretion
      of infectious particles that packaged the replicon RNA, albeit with a low
      production efficiency of 0.4 * 10(2) to 1.1 * 10(2) infectious units/ml; the
      produced particles had only single-round infectivity with no cell-to-cell spread.
      This trans-complementation system for PRRSV provides a useful platform for
      studies to define the packaging signals and motifs present within the viral
      genome and N protein, respectively, and to develop viral replicon-based antiviral
      vaccines that will stop the infection and spread of this pathogen.

PMID- 21717345
TI  - Measuring size-dependent permeability of the tight junction using PEG profiling.
AB  - Tight junctions restrict the paracellular movement of ions, solutes, drugs, and
      larger material across epithelia and endothelia. For practical purposes, the
      barrier can be modeled as having two components. The first is a system of small 4
      A radius pores lined or created by claudins. The pores show variable ionic
      charge selectivity and electrical resistance based on the pattern of claudin
      proteins expressed in a particular junction. Transport of compounds that are
      larger than 4  A are not subject to discrimination based on size or charge; they
      are likely passing through transient breaks in the tight junction barrier. The
      magnitude of the first and second pathways varies among epithelia and is altered
      in response to physiological and pathological stimuli. Unfortunately, most
      studies of permeability use few tracer sizes and thus provide limited information
      on size-dependent changes in permeability. Here we describe a method for
      simultaneously measuring the size-dependence of apparent permeability using a
      continuous series of polyethylene polymers which allows quantification of both
      the pore and leak pathways.

PMID- 21717346
TI  - Biochemical analysis of claudin-binding compatibility.
AB  - Tissue barrier function is directly mediated by tight junction transmembrane
      proteins known as claudins. Cells that form tight junctions typically express
      multiple claudin isoforms, which suggests that heterotypic (head-to-head) binding
      between different claudin isoforms may play a role in regulating paracellular
      permeability. To test whether claudins are heterotypically compatible, we
      developed an assay system using HeLa cells, a claudin-null cell line which
      expresses other tight junction proteins, including occludin, junction adhesion
      molecule A, and zonula occludens-1, -2, and -3. HeLa cells stably transfected to
      express different claudins are cocultured, then subsequently analyzed for the
      ability to coimmunopurify. Using this approach, we have found that claudin-1,
      claudin-3, and claudin-5 are heterotypically compatible. In contrast, two closely
      related claudins, claudin-3 and claudin-4, are incompatible. Differential claudin
      binding specificity is likely to have downstream effects on the regulation of
      tight junction composition and permeability.

PMID- 21717347
TI  - Electrophysiological characterization of claudin ion permeability using stably
      transfected epithelial cell lines.
AB  - Claudins are tight junction membrane proteins that act as paracellular pores and
      barriers and regulate epithelial permeability to small ions. A key step in
      understanding the function of any claudin isoform is the in vitro measurement of
      its ion permeability and selectivity. Herein, we describe methods to generate
      clonal lines with stable inducible overexpression of claudins in Madin-Darby
      canine kidney epithelial cells, measure conductance and diffusion potentials in
      Ussing chambers, correct for liquid junction potentials, and derive
      quantitatively accurate values for individual ion permeabilities.

PMID- 21717348
TI  - The tight junction, intercellular seal as a cell signaling player: protocols for
      examination of its status.
AB  - Tight junctions (TJs) are intercellular structures in epithelial and endothelial
      cells, primarily playing -critical roles in cell-cell adhesion. Among their
      molecular components, claudins are the main constituents as integral membrane
      proteins, encoded by at least 24 members of a single gene family. Accumulated 
      evidence has demonstrated that TJ proteins such as claudins are directly involved
      in the regulation of -cellular functions such as proliferation, differentiation,
      and apoptosis, due to their ability to recruit various signaling molecules that
      have proliferative and differentiative capacities, including transcription
      factors, lipid phosphatases, and cell cycle regulators. It is thus clear that TJs
      are not simple static constituents to establish cell adhesion structures, rather
      also functioning in cell signaling component that has functions in receiving
      environmental cues and transmitting signals inside the cells.

PMID- 21717349
TI  - Interactions between Clostridium perfringens enterotoxin and claudins.
AB  - Clostridium perfringens enterotoxin (CPE), a single polypeptide of approximately
      35 kDa in size, is -associated with type A food poisoning and such non-foodborne
      gastrointestinal diseases as antibiotic-associated diarrhea and sporadic
      diarrhea. CPE action begins with binding of the toxin to a claudin -receptor,
      forming a ~90 kDa small complex that then rapidly oligomerizes into a hexamer of
      ~450 kDa termed CH-1 (CPE hexamer-1). CH-1 is essentially a pore through which
      calcium gains entry to the cytoplasm, altering cell permeability and resulting in
      cell death by oncosis or apoptosis. Additionally, tight junctions are disrupted,
      allowing CPE access to the basolateral membrane so it can produce additional CH-1
      -complexes and also the CH-2 complex (~600 kDa) that contains occludin. We have
      recently demonstrated the presence of claudins-3 and -4 in both the CH-1 and CH-2
      CPE complexes formed after CPE treatment naturally sensitive Caco-2 cells.
      Interestingly, claudin-1, which binds CPE poorly (if at all), was also present in
      these complexes.

PMID- 21717350
TI  - Biophysical methods to probe claudin-mediated adhesion at the cellular and
      molecular level.
AB  - Claudins are a family of tetraspan membrane proteins that localize at tight
      junctions in an epithelial monolayer forming a selective barrier to diffusion of
      solutes via the intercellular spaces. It is widely accepted that the interaction
      between the extracellular loops of claudin molecules from adjacent cells is
      critical for this function. Though previous experiments utilizing traditional
      biological, biochemical, morphological, and electrophysiological approaches have
      provided significant insights into the role of claudins in regulating ion
      permeability, the interaction kinetics between these molecules has not been
      characterized. In this chapter, we describe two experimental procedures to study
      the adhesion forces imparted by claudins: (a) dual micropipette assay to quantify
      the adhesion forces at the cellular level and (b) single molecule force
      spectroscopy using atomic force microscopy to characterize the interaction
      kinetics at the molecular level. Though the experimental procedures are described
      for claudins, they can be easily modified for studying the interaction properties
      of a wide variety of other proteins.

PMID- 21717351
TI  - Detection of tight junction barrier function in vivo by biotin.
AB  - Tight junctions (TJs) are the most apical component of the junctional complexes
      in mammalian epithelial cells and form selective paracellular barriers
      restricting the passage of solutes and ions across the epithelial sheets.
      Claudins, a TJ integral membrane protein family, play a critical role in
      regulating paracellular barrier permeability. In the in vitro cell culture
      system, transepithelial electrical resistance (TER) measurement and the flux of
      radioisotope or fluorescent labeled molecules with different sizes have been
      widely used to determine the TJ barrier function. In the in vivo system, the
      tracer molecule Sulfo-NHS-Biotin was initially used in Xenopus embryo system and
      subsequently was successfully applied to a number of animal tissues in situ and
      in different organisms under the experimental conditions to examine the
      functional integrity of TJs by several laboratories. In this chapter, we will
      describe the detailed procedures of applying biotin as a paracellular tracer
      molecule to different in vivo systems to assay TJ barrier function.

PMID- 21717352
TI  - The coculture method to examine interactions between claudin isoforms in tight
      junction-free HEK293 cells and tight junction-bearing MDCK II cells.
AB  - The paracellular transport of water, ions, and small solutes is regulated by
      tight junctions (TJs) in -epithelial, endothelial, and mesothelial cells. Both
      the prolonged increase and decrease of the paracellular permeability are involved
      in various diseases. Claudins, a family of at least 24 integral membrane proteins
      in TJs, are major components of TJs and usually more than two claudin isoforms
      are found in TJs. The combination and mixing ratios of claudin isoforms determine
      the paracellular permeability in TJs. To create the paracellular permeability
      barrier, claudins must interact laterally in one membrane (cis-interaction) and
      also must interact by head-to-head binding between adjacent cells (trans
      interaction). Therefore, examination of claudin-claudin interactions provides
      insights into the mechanism of regulation of the paracellular permeability. This
      study introduced coculture systems using TJ-bearing MDCK II cells and TJ-free
      HEK293 cells to examine claudin-claudin interactions.

PMID- 21717353
TI  - Claudin-4: functional studies beyond the tight junction.
AB  - Claudin-4 is an unusual member of the claudin family; in addition to its role in
      epithelial tight junction barrier function, it is a receptor for the Clostridium
      perfringens enterotoxin. We have also found that claudin-4 is regulated in
      mucosal epithelium M cells, both in increased expression of the protein and in
      redistribution into endocytosis vesicles. Our ongoing studies are studying the
      potential for developing ligands specific to claudin-4 for targeted delivery of
      cargo such as proteins and poly(DL-lactide-co-glycolide) nanoparticles to mucosal
      M cells. Methods for the study of claudin-4 movement within epithelial cells, and
      delivery of nanoparticles through targeted binding of claudin-4 are described.

PMID- 21717354
TI  - Methods to analyze subcellular localization and intracellular trafficking of
      Claudin-16.
AB  - The integral tight junction protein Claudin-16 (Cldn16) is predominantly
      expressed in renal epithelial cells of the thick ascending limb of Henle's loop
      where, together with claudin-19, it forms a cation-selective pore that allows
      influx of Na+ from the interstitial fluid into the lumen of the kidney tubule.
      This leads to an electrochemical gradient that drives the reabsorbtion of Mg2+
      and Ca2+ ions from the renal filtrate. Mutations in the Cldn16 gene have been
      identified in patients suffering from familial hypomagnesemia with hypercalciuria
      and nephrocalcinosis, with excessive renal wastage of Mg2+ and Ca2+ being a
      hallmark of this condition. Studies into the mechanism by which mutations impair
      Cldn16 function have shown that although several mutations affect paracellular
      ion transport, many interfere with intracellular trafficking of Cldn16,
      ultimately compromising its localization to TJs. Here, we describe the
      experimental approaches that can be used to monitor intracellular localization
      and trafficking of Cldn16. These methods can easily be adapted to study other
      claudins, provided suitable antibodies are available.

PMID- 21717355
TI  - Claudin family proteins in Caenorhabditis elegans.
AB  - In the last decade, the claudin family of integral membrane proteins has been
      identified as the major protein component of the tight junctions in all
      vertebrates. The claudin superfamily proteins also function to regulate channel
      activity, intercellular signaling, and cell morphology. Subsequently, claudin
      homologues have been identified in invertebrates, including Drosophila and
      Caenorhabditis elegans. Recent studies demonstrate that the C. elegans claudins,
      clc-1 to clc-5, and similar proteins in the greater PMP22/EMP/claudin/calcium
      channel gamma subunit family, including nsy-1-nsy-4 and vab-9, while highly
      divergent at a sequence level from each other and from the vertebrate claudins,
      in some cases play roles similar to those traditionally assigned to their
      vertebrate homologues. These include regulating cell adhesion and passage of
      small molecules through the paracellular space. The claudin superfamily proteins
      also function to regulate channel activity, intercellular signaling, and cell
      morphology. Study of claudin superfamily proteins in C. elegans should continue
      to provide clues as to how core claudin protein function can be modified to serve
      various specific roles at regions of cell-cell contact in metazoans.

PMID- 21717356
TI  - In vivo imaging of tight junctions using claudin-EGFP transgenic medaka.
AB  - Tight junctions (TJs) function as a physiological barrier between epithelial and
      endothelial sheets by restricting the diffusion of fluid through the
      intercellular space. Recent morphological studies associated with TJs have
      revealed that the TJ is a dynamic rather than a static structure; indeed, several
      in vitro studies indicate that proper TJ function requires dynamic TJ behavior.
      Direct observation of the dynamic behavior of TJs is necessary to understand the
      essential roles of TJs in physiological contexts, such as during embryogenesis
      and metastasis. Here we describe a protocol for the generation of transgenic
      medaka (Oryzias latipes) that express claudin-EGFP. This fluorescent fusion
      protein enables real-time imaging of TJs in the living embryo. Claudin-EGFP
      transgenic medaka will be a useful tool to screen for mutations and for small
      molecules affecting cell-cell adhesion.

PMID- 21717357
TI  - Claudins in a primary cultured puffer fish (Tetraodon nigroviridis) gill
      epithelium.
AB  - A primary cultured gill epithelium from the model organism Tetraodon nigroviridis
      (spotted green puffer fish) has been developed for the study of claudin tight
      junction (TJ) proteins and their potential role in the regulation of paracellular
      permeability across the gills of fishes. The cultured preparation is composed of
      polygonal epithelial cells that exhibit TJ protein immunoreactivity around the
      periphery and develop a surface morphology of concentric apical microridges.
      There is an absence of cells exhibiting intense Na+-K+-ATPase immunoreactivity
      and taken together, these characteristics indicate that the epithelium is
      composed of gill pavement cells only. In Tetraodon, 52 genes encoding for claudin
      isoforms (Tncldn) have been identified and 32 of these genes are expressed in
      whole gill tissue. Of these genes, 12 are responsive to alterations in
      environmental salinity in vivo (Tncldn3a, -3c, -6, -8d, -10d, -10e, -11a, -23b, 
      27a, -27c, -32a, and -33b). All claudin isoforms found in whole gill tissue can
      be found in cultured pavement cell gill epithelia with the exception of Tncldn6, 
      10d, and -10e. The cultured preparation is suitable for studying the "molecular
      machinery" of TJ proteins in fish gill pavement cells.

PMID- 21717358
TI  - Manipulating claudin expression in avian embryos.
AB  - Since the discovery of Claudin-1 and -2 by Tsukita and colleagues in the late
      1990s [Furuse et al. J Cell Biol 141:1539-50,1998], claudin family members have
      been found to have critical roles in maintaining the integrity of epithelial and
      endothelial tight junctions [Furuse and Moriwaki Ann N Y Acad Sci 1165:58-61,
      2009; Morita et al. Proc Natl Acad Sci USA 96:511-6, 1999; Tsukita and Furuse Ann
      N Y Acad Sci 915:129-35, 2000; Turksen and Troy J Cell Sci 117:2435-47, 2004].
      The properties of distinct claudin family members in tight junction permeability
      and specificity have been extensively studied in vitro using cell culture models.
      In vivo, claudin family members are dynamically regulated during embryogenesis
      and alterations in their expression patterns can have detrimental effects on the
      formation and physiological function of the tissues in which they are expressed.
      The chick embryo provides an excellent system to dissect the roles of specific
      family members in vivo and to explore the effects of modulating claudin
      expression during the epithelial-to-mesenchymal and mesenchymal-to-epithelial
      transitions that are associated with tissue morphogenesis and differentiation. We
      are using the chick embryo to understand the roles of the claudin family of tight
      junction proteins during gastrulation and left-right patterning during
      embryogenesis. Here, we describe methodologies for manipulating claudin gene
      expression in specific target tissues during chick embryogenesis.

PMID- 21717359
TI  - Identification of claudins by western blot and immunofluorescence in different
      cell lines and tissues.
AB  - Claudins are integral proteins of the TJ. Each epithelia in the organism
      expresses a unique set of claudins that determines the degree of sealing of the
      paracellular pathway and the ionic selectivity of the tissue. TJs are dynamic
      structures whose organization and composition change in response to alterations
      in the environment as well as under physiological and pathological conditions.
      Changes in claudin expression and subcellular distribution can be analyzed in
      western blot and immunofluorescence experiments, employing a wide array of
      available specific antibodies against claudins. In this chapter, we describe in
      detail protocols used for western blot and immunofluorescence detection of
      claudins in epithelial cell lines and in various tissue samples.

PMID- 21717360
TI  - Expression and function of claudins in hepatocytes.
AB  - Tight junctions of hepatocytes play crucial roles in the barrier to keep bile in
      bile canaliculi away from the blood circulation, which we call the blood-biliary
      barrier. Tight junction proteins of hepatocytes are regulated by various
      cytokines and growth factors via distinct signal transduction pathways. To
      investigate changes in expression and function of tight junction proteins
      including claudins via signal transduction pathways in hepatocytes during EMT
      induced by TGF-beta, we examined effects of TGF-beta on expression and
      localization of the integral tight junction proteins, claudin-1, -2, and
      occludin, as well as the fence function by using primary cultures of adult rat
      hepatocytes.

PMID- 21717361
TI  - Analysis of changes in the expression pattern of claudins using salivary acinar
      cells in primary culture.
AB  - Primary saliva is produced from blood plasma in the acini of salivary glands and
      is modified by ion adsorption and secretion as the saliva passes through the
      ducts. In rodents, acinar cells of salivary glands express claudin-3 but not
      claudin-4, whereas duct cells express both claudins-3 and -4. The distinct
      claudin expression patterns may reflect differences in the permeability of tight
      junctions between acinar and duct cells. To analyze the role of claudins in
      salivary glands, we established a system for the primary culture of parotid
      acinar cells, where the expression patterns of claudins are remarkably changed.
      Real-time RT-PCR and immunoblot analyses reveal that the expression levels of
      claudins-4 and -6 increased, whereas claudins-3 and -10 decreased. We found that
      the signal to induce those changes is triggered during cell isolation and is
      mediated by Src and p38 MAP kinase. Here, we introduce the methods used to
      determine the signal pathway that induces the change in claudin expression.

PMID- 21717362
TI  - Development of biological tools to study claudins in the male reproductive tract.
AB  - It is estimated that between 12 and 15% of couples are infertile. More than half
      of these are related to problems associated with male reproductive dysfunction.
      Of those, 40% occur from idiopathic or unexplained causes. While spermatozoa are
      formed in the testis, testicular spermatozoa are immature and cannot swim or
      fertilize. These critical functions are acquired as spermatozoa transit through
      the epididymis in the specific luminal environment created in part by the tight
      junctions of the blood-epididymis barrier. To understand the normal and
      pathological conditions attributable to human and animal epididymal function, we
      have needed to develop biological tools to characterize the physiological,
      cellular, and molecular functions of tight junctions and claudins (Cldns) in the
      epididymis. We have shown that by developing epididymal cell lines we have gained
      valuable insight into the functions of epididymal Cldns, the regulation of the
      Cldn1 gene and how these can be mistargeted in infertile men. Here we describe
      some of the techniques that have been used to address these critical aspects of
      epididymal Cldns.

PMID- 21717363
TI  - Using molecular tracers to assess the integrity of the intestinal epithelial
      barrier in vivo.
AB  - The examination of the epithelial barrier has been a primary site of focused
      research for years. Despite the importance of this site to numerous intestinal
      diseases, the determination of the integrity of this barrier has been clouded by
      controversies as to the validity of certain techniques and the ease of use
      regarding others. To determine the barrier integrity in vivo, we have adapted a
      simple tracer-based microscopic assay that was initially used in other systems to
      the in vivo intestinal epithelium. This technique is widely adaptable to other
      tracer molecules that can be applied to the tissue and consequently generates
      images depicting barrier maintenance or functional breach.

PMID- 21717364
TI  - Laboratory methods in the study of endometrial Claudin-4.
AB  - Immunohistochemistry is a suitable method for the detection of proteins from the
      Claudin family and several antibodies are commercially available for the
      detection of Claudin congeners. Immunodetection of Caludin-4 in the paraffin
      embedded specimens might be a useful tool for studying the role of these proteins
      in the cyclic transformation of the endometrium and its role in the endometrial
      receptivity; furthermore, other components of the junctional zone involved in the
      transformational process of the endometrium can be detected by means of
      immunohistochemistry/immunofluorescence with several polyclonal or monoclonal
      antibodies. The aim of this chapter is to comprehensively overview the materials
      and methods to perform the endometrial biopsy and to detect Claudin-4 in paraffin
      embedded samples of endometrium. Additionally, the interpretation of the results
      is addressed.

PMID- 21717365
TI  - Role of claudins in oxidant-induced alveolar epithelial barrier dysfunction.
AB  - Claudins are the most important components of the tight junctions at the
      interface of the basolateral and apical membranes of polarized epithelial and
      endothelial cells. They determine the barrier properties of cell-cell contact
      existing between two neighboring cells and regulate paracellular permeability.
      Although maintenance of barrier properties requires intact epithelial tight
      junctions, relatively little is known about the role of claudins expressed in the
      alveolar epithelium in the regulation of epithelial permeability in response to
      inflammatory stimuli and oxidative stress, or injury. The present study was
      undertaken to determine whether differential expression of tight junction
      claudins is a mechanism for regulation of oxidant-induced pulmonary epithelial
      hyperpermeability. Here, we show that claudin-2 plays an important role in the
      regulation of epithelial barrier function during oxidative stress.

PMID- 21717366
TI  - Tracing the endocytosis of claudin-5 in brain endothelial cells.
AB  - Claudin-5 is a transmembrane tight junction protein highly expressed in brain
      endothelial cells, the site of the blood-brain barrier. The properties of the
      brain endothelial tight junction complex are considered to be dependent on
      claudin-5 cell-cell interaction, putting this protein in a position to play a
      major role in the maintenance of brain endothelial barrier integrity. Thus,
      alterations in claudin-5 function can lead to "opening" of the paracellular route
      and increased brain endothelial barrier permeability. Recent work from the
      authors's laboratory has established that caveolae-dependent
      internalization/recycling of claudin-5 is a mechanism underlying transient
      increases in brain endothelial paracellular permeability in the presence of pro
      inflammatory mediators. The biochemical and microscopic techniques presented here
      were used to investigate trafficking of claudin-5 during those changes in
      paracellular permeability.

PMID- 21717367
TI  - Quantitative in situ analysis of claudin expression at the blood-retinal barrier.
AB  - It is apparent that claudins are involved in signalling to and from cellular
      tight junctions (TJs) and control cell behaviour such as proliferation,
      differentiation, and migration. Methods to identify and measure specific claudins
      in TJs would, therefore, be useful to monitor TJ structure and functional
      integrity under physiological and pathological conditions. The molecular pathways
      involved in claudin signalling are not understood and are likely to become a
      focus for intensive research as better understanding of tight junction structure
      and function may provide opportunities for better drug delivery and absorption.
      In this chapter, we describe our method for quantitative analysis of specific
      claudins in TJ during the breakdown of the blood-retinal barrier in a mouse model
      of inflammatory uveitis, experimental autoimmune uveoretinitis (EAU).

PMID- 21717368
TI  - MMP-mediated disruption of claudin-5 in the blood-brain barrier of rat brain
      after cerebral ischemia.
AB  - The blood-brain barrier (BBB) has become a major focus of attention in cerebral
      pathophysiology and disease progression in the central nervous system.
      Endothelial tight junctions, the basal lamina, and perivascular astrocytes are
      jointly referred to as BBB or neurovascular unit. Around the cerebral endothelial
      cells is the basal lamina composed primarily of laminin, fibronectin, and heparan
      sulfate. The basal lamina provides a structural barrier to extravasation of
      cellular blood elements and anchors endothelial cells to astrocytes. Barriers
      limiting transport into and out of the brain are found at the tight junction
      proteins and at the basal lamina. The relative contribution of these two sites
      has not been studied, but it is likely that both are disrupted to some extent in
      various injury scenarios. We have shown that activation of matrix
      metalloproteinases (MMPs) opens the BBB by degrading tight junction proteins
      (claudin-5 and occludin) and increases BBB permeability after stroke, and that an
      MMP inhibitor prevents degradation of tight junction proteins and attenuates BBB
      disruption.

PMID- 21717369
TI  - Claudin-5 expression in in vitro models of the blood-brain barrier.
AB  - Claudins are transmembrane proteins that form the backbone of the tight junctions
      (TJs) at the blood-brain barrier (BBB). TJs are cellular structures that
      physically obstruct the inter-endothelial space and restrict the paracellular
      diffusion of blood-borne substances from the peripheral circulation into the CNS.
      TJs are also dynamic structures that rapidly respond to external signals that
      produce changes in BBB permeability. We focus here on the biochemical and
      immunohistochemical properties of claudin-5 as expressed in three in vitro models
      of the BBB, and show that the contact co-culture of endothelial cells with glial
      cells significantly increases claudin-5 expression.

PMID- 21717371
TI  - Enhanced immunohistochemical resolution of claudin proteins in glycolmethacrylate
      embedded tissue biopsies.
AB  - There are a number of disadvantages with conventional tissue immunohistochemistry
      for accurate -localisation of claudin proteins. Traditionally, tissue
      cryopreservation or formaldehyde fixation with wax embedding is utilised prior to
      sectioning and antibody localisation. Wax embedding gives better morphological
      preservation than frozen tissue, but the required use of chemical cross-linking
      fixatives renders many antigens inaccessible to antibody binding or results in
      subsequent disruption of antibody localisation patterns due to the use of harsh
      antigen retrieval methods. Use of frozen or wax-embedded tissue also requires the
      cutting of relatively thick>6-MUm sections, making the interrogation of serial
      sections very limited. The use of glycolmethacrylate (GMA) tissue embedding with
      fixation in acetone is compatible with epitope preservation for many antibody
      reagents that are often destroyed by chemical cross-linking fixatives. GMA is a
      water-miscible embedding resin that maintains tissue hydration during processing,
      thus reducing tissue shrinkage, while embedding and cutting in the polymerised
      resin physically supports the tissue, thus improving morphology. This method also
      facilitates the cutting of 2-MUm sequential sections for analysis of multiple
      antigens and maximises the information available from small tissue biopsies from
      human clinical sources.

PMID- 21717370
TI  - HIV-1-induced alterations of claudin-5 expression at the blood-brain barrier
      level.
AB  - HIV-1 crosses the blood-brain barrier (BBB) early in the course of systemic
      infection and resides in brain macrophages and microglia. The integrity of the
      brain endothelium is regulated by intercellular tight junctions, which also play
      a critical role in HIV-1-entry into the brain. Disruption of tight junctions,
      including changes in claudin-5 expression, is common in HIV-1-infected patients.
      Recent evidence indicates that both exposure to HIV-1 and HIV-1 specific
      proteins, such as Tat protein, can contribute to alterations of expression and
      distribution of claudin-5 in brain endothelial cells and brain microvessels.

PMID- 21717372
TI  - Claudin-16/paracellin-1, cloning, expression, and its role in tight junction
      functions in cancer and endothelial cells.
AB  - Metastatic spread of cancer is the major reason for patient mortality in human
      breast cancer. We examined expression of claudin-16 in human breast cells and
      tissues to identify a possible link between expression and aggressiveness in
      cells and between claudin-16 levels and patient prognosis. Forced expression of
      claudin-16 in breast cancer cells resulted in a less aggressive phenotype and
      reduced in vivo tumour volume. Claudin-16 expression was reduced in human breast
      cancer, particularly in patients with aggressive tumours and high mortality
      (Martin et al. J Cell Biochem 105:41-52,2008). This suggests that claudin-16
      plays a role beyond that of an initial metastasis repressor in this cancer type.

PMID- 21717373
TI  - Dynamics of claudins expression in colitis and colitis-associated cancer in rat.
AB  - Claudins comprise a multigene family of 24 species and have been shown to
      constitute the backbone of tight junction strands in simple epithelial cells and
      to be directly involved in their barrier functions. Apical-most tight junction
      protein complexes (TJs) are implicated in inflammatory bowel disease (IBD)
      pathophysiology. Except for claudin-8, TJs explored in this study (including ZO
      1, claudin-1, -2, -3, -7, -12, and -15) were found to be expressed in rat colonic
      tissues. ZO-1 and claudin-7 were ubiquitously expressed in all study groups. As
      depicted in Fig. 1b, expressions of claudin-2, -12, and -15 significantly
      diminished after combined treatment with dextran sulfate sodium (DSS) and
      busulfan (BU) (lane 5), compared with either agent alone (lanes 2 and 4). Despite
      the lack of significance, there appeared to be a subtle dose-dependent decrease
      with DSS treatment (lanes 2 and 3). In contrast to these results obtained from
      DSS colitis, expression of claudin-1 was significantly downregulated, while
      expression of claudin-15 was upregulated in colitis-associated cancer tissues in
      the azoxymethane (AOM)/DSS model (Fig. 2b). It is very intriguing that claudins'
      expression dynamics were mutually exclusive between colitis and colitis
      associated cancer in rats. However, the biological significance of disease
      specific claudin expression profiles will remain elusive until the specific
      expression and function of each claudin in a tissue- and cell-type relationship
      are comprehensively clarified. Currently, the physiologic consequences of the
      diversity of TJ barrier function resulting from multiple combinations of claudins
      are only beginning to be recognized. Full unraveling of these complexities could
      inspire a new paradigm of inflammation and cancer, and eventually translate to
      clinical practice on IBD.

PMID- 21717374
TI  - Anti-claudin-4-conjugated highly luminescent nanoparticles as biological labels
      for pancreatic cancer sensing.
AB  - Anti-claudin-4, whose corresponding antigen receptors are known to be
      overexpressed in both primary and metastatic human pancreatic cancer, is utilized
      for targeted delivery and imaging of pancreatic cancer. In this protocol, we
      describe the use of quantum dots (QDs) as sensitive optical contrast agent for
      imaging pancreatic cancer in vitro and in vivo by using anti-claudin-4 as
      targeting ligands. The claudin-4-mediated targeting is demonstrated in using both
      in vitro confocal microscopy and in vivo tumor imaging system. This targeted QD
      platform will be further modified for the purpose of developing as an early
      detection imaging tool for pancreatic cancer.

PMID- 21717375
TI  - Effects of pain controllability and discrepancy in social support on depressed
      mood among patients with chronic pain.
AB  - BACKGROUND: Preference of types of social support may vary across recipients, and
      social support that is less than the amount preferred may be associated with
      depressed mood. PURPOSE: This study aimed to investigate the interaction effects
      between pain controllability and discrepancy in social support and the additive
      utility of discrepancy in social support over perceived social support in
      predicting depressed mood among patients with chronic pain. METHOD: A total of
      173 patients seeking treatment at two outpatient pain management clinics in
      Hawaii participated. RESULTS: The results indicated that (1) patients with low
      pain controllability preferred significantly more social support than those with
      high pain controllability, for all types of social support; (2) patients
      preferred significantly more informational and emotional support than
      instrumental support for both pain controllability levels; (3) discrepancy in
      informational or instrumental support was not associated with depressed mood,
      whereas discrepancy in emotional support was significantly associated with more
      depressed mood for low pain controllability, but not for high pain
      controllability; and (4) discrepancy in emotional support added a significant
      increment of variance in predicting depressed mood over and above perceived
      emotional support, whereas discrepancy in informational or instrumental support
      did not. CONCLUSION: Findings suggest the relative importance of discrepancy in
      emotional support from a significant other, especially for patients with low pain
      controllability.

PMID- 21717376
TI  - Photodegradation of fleroxacin injection: different products with different
      concentration levels.
AB  - Photodegradation of fleroxacin is investigated in different injections and
      solutions. After UV irradiation, fleroxacin was degraded to afford two major
      products in large-volume injection (specification, 200 mg:100 ml), while degraded
      to afford another major product in small-volume injection (specification, 200
      mg:2 ml). The photodegradation products were detected and isolated by reversed
      phase HPLC. Based on the spectral data (FT-IR, MS(n), TOF-MS, (1)H/(13)C, DEPT,
      and 2D NMR), the structures of these products were: 8-fluoro-9-(4-methyl
      piperazin-1-yl)-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid
      (impurity-I); 6-fluoro-1-(2-fluoro-ethyl)-7-(2-methylamino-ethylamino)-4-oxo-1,4
      dihydro-quinoline-3-carboxylic acid (impurity-II); and 6,8-difluoro-1-(2-fluoro
      ethyl)-7-(2-methylamino-ethylamino)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
      (impurity-III), respectively. Different photodegradation pathways of fleroxacin
      were proposed, which led to the different stability characteristics of fleroxacin
      in the injections. The fluorine atom at C8 is more photolabile in dilute
      injection, so defluorination and cyclization reactions are prone to take place,
      whereas photo irradiation only cause ring-opening oxidation reaction of
      piperazine side chain in concentrated injection.

PMID- 21717377
TI  - Endoscopic ultrasound in cystic pancreatic lesions: operator training needs to be
      improved, EUS-guided sampling should be standardized, and decision-making should
      be multidisciplinary and evidence-based.

PMID- 21717378
TI  - Interobserver agreement for endosonography in the diagnosis of pancreatic cysts.
AB  - BACKGROUND AND STUDY AIMS: Endosonography is considered a valuable technique in
      the evaluation of pancreatic cysts. The aim of the present study is to assess
      interobserver agreement, in three different observer groups, regarding EUS for
      characterization of pancreatic cysts. PATIENTS AND METHODS: Video sequences of 40
      EUS procedures for pancreatic cysts were prepared. Three groups of observers had
      different levels of EUS experience: group 1 comprised four experts with extensive
      EUS experience, group 2 had four "semi-experts" with limited EUS experience, and
      group 3 (novices) comprised four non-expert resident physicians without EUS
      experience. Features scored included septations, nodules, solid components, and
      pancreatic duct communication. A presumptive diagnosis had to be specified. The
      intraclass correlation coefficient (ICC) was used, with agreement classed as
      excellent (> 0.80), good (0.61 - 0.80), moderate (0.41 - 0.60), fair (0.20 -
      0.40), and poor (< 0.20). RESULTS: Agreement regarding nodules was good among
      experts (ICC 0.65) and fair in the semi-expert and novice groups (ICC 0.32 and
      0.37, respectively). For presence of solid components there was significantly
      higher agreement among experts (ICC 0.52) compared with the other two groups
      (semi-experts 0.09, and novices 0.03). Agreement regarding specific diagnosis was
      moderate in the expert group (0.43), poor among the semi-experts (0.09), and fair
      among the novices (0.30). CONCLUSIONS: Interobserver agreement among expert
      endosonographers was mostly moderate for characteristics of pancreatic cysts.
      However, interobserver agreement for experts was equal to or higher than that in
      the semi-expert and in the novice groups.

PMID- 21717379
TI  - Radiofrequency ablation is effective for the treatment of high-grade dysplasia in
      Barrett's esophagus after failed photodynamic therapy.
AB  - Endoscopic radiofrequency ablation (RFA) is an effective treatment for high-grade
      dysplasia in Barrett's esophagus in ablation-naive patients, but no studies have
      evaluated its use in patients in whom ablative therapy has previously failed. We
      describe 14 patients with residual high-grade dysplasia following aminolevulinic
      acid or Photofrin (porfimer sodium) photodynamic therapy (PDT). An overall
      complete reversal of dysplasia was achieved in 86 % with a combination of RFA and
      rescue endoscopic mucosal resection. The median total follow-up is 19 months. The
      rate of strictures was 7 % (1/14) and there was a low rate of buried glands (0.5
      % follow-up biopsies). These data suggest RFA is both safe and effective for
      eradication of high-grade dysplasia in patients in whom PDT has failed.

PMID- 21717380
TI  - How many personnel and how much monitoring are really necessary for
      nonanesthesiologist administration of propofol for gastrointestinal endoscopy?

PMID- 21717384
TI  - Fractures and Fanconi syndrome due to prolonged sodium valproate use.
AB  - BACKGROUND: Sodium valproate (VPA) is commonly used to treat epilepsy in
      children. Renal dysfunction is a rare side eff ect but can present as tubulopathy
      such as Fanconi syndrome. CASE REPORT: We report on an 8-year-old disabled girl
      with myoclonic epilepsy who was referred for investigation of recurrent low
      impact fractures of the distal femur which were initially thought to be caused by
      her severe immobility. However, she was subsequently found to have
      hypophosphataemia secondary to Fanconi syndrome due to prolonged VPA use. After
      VPA withdrawal renal function and serum phosphate levels normalised and X-rays
      improved dramatically. CONCLUSION: The possibility of drug-induced osteoporosis
      and fractures should always be considered in disabled children, even in the
      presence of severe immobility.

PMID- 21717385
TI  - Medical, psychological and intellectual development of 5-year-old children born
      after intracytoplasmic sperm injection.
AB  - BACKGROUND: The neurodevelopmental outcome of children born after
      intracytoplasmic sperm injection (ICSI) is controversial. PATIENTS AND METHODS:
      Thus, we compared the medical and developmental outcome at a mean age of 5 years
      and 6 months of 35 singletons born after an ICSI procedure performed at the
      Tubingen Medical Center with those of 37 naturally conceived (NC) matched control
      singletons born at the Tubingen Medical Center. Children with congenital
      anomalies which could interfere with mental development were excluded, these were
      reported earlier. Each child was assessed neurologically and physically.
      Cognitive function was assessed using the Kaufman assessment battery for children
      (K-ABC). Behaviour was tested using a German behavioural questionnaire for
      preschoolers (VBV). RESULTS: Medical and cognitive outcome, and behaviour pattern
      were similar in both groups. Nevertheless, there were sex-related differences in
      favour of ICSI children: ICSI boys had better social competence than the control
      boys, while ICSI girls had less emotional problems than the control girls.
      CONCLUSIONS: Once severe congenital anomalies were excluded, there were no
      differences in physical and neurodevelopmental outcome of 5-year-old ICSI
      children compared with controls.With regard to behaviour and emotional
      development, ICSI children seem to be similar or might be even more stable and
      socially competent than the control children. As our study is limited by the
      small sample size, further research is needed to confirm our results.

PMID- 21717386
TI  - A small-scale clinical trial to determine the safety and efficacy of testosterone
      replacement therapy in hypogonadal men with spinal cord injury.
AB  - Men with spinal cord injury are at an increased risk for secondary medical
      conditions, including metabolic disorders, accelerated musculoskeletal atrophy,
      and, for some, hypogonadism, a deficiency, which may further adversely affect
      metabolism and body composition. A prospective, open label, controlled drug
      intervention trial was performed to determine whether 12 months of testosterone
      replacement therapy increases lean tissue mass and resting energy expenditure in
      hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and
      hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled.
      Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12
      months. Measurements of body composition and resting energy expenditure were
      obtained at baseline and 12 months. The testosterone replacement therapy group
      increased lean tissue mass for total body (49.6 +/- 7.6 vs. 53.1 +/- 6.9 kg; p <
      0.0005), trunk (24.1 +/- 4.1 vs. 25.8 +/- 3.8 kg; p < 0.005), leg (14.5 +/- 2.7
      vs. 15.8 +/-2.6  kg; p = 0.005), and arm (7.6 +/- 2.3 vs. 8.0 +/- 2.2 kg; p <
      0.005) from baseline to month 12. After testosterone replacement therapy, resting
      energy expenditure (1328 +/- 262 vs. 1440 +/- 262 kcal/d; p < 0.01) and percent
      predicted basal energy expenditure (73 +/- 9 vs. 79 +/- 10%; p < 0.05) were
      significantly increased. In conclusion, testosterone replacement therapy
      significantly improved lean tissue mass and energy expenditure in hypogonadal men
      with spinal cord injury, findings that would be expected to influence the
      practice of clinical care, if confirmed. Larger, randomized, controlled clinical
      trials should be performed to confirm and extend our preliminary findings.

PMID- 21717387
TI  - The Stillbirth Collaborative Research Network (SCRN) placental and umbilical cord
      examination protocol.
AB  - The Stillbirth Collaborative Research Network (SCRN) was organized to study the
      scope and causes of stillbirth (SB) in the United States. The objective of this
      report is to describe the approach used for the placental examination performed
      as part of the study. The SCRN consists of a multidisciplinary team of
      investigators from five clinical sites, the National Institute of Child Health
      and Human Development, and the Data Coordination and Analysis Center. The study
      is a population-based cohort and nested case-control study, with prospective
      enrollment of women with SB and live births (LB) at the time of delivery.
      Detailed and standardized postmortem examination was performed on SB and
      placental examination in both groups. A total of 663 women with SB and 1932 women
      with LB were enrolled into the case-control study. In the SB group, there were
      707 fetuses. Of these cases, 654 (98.6%) had placental examination. Of these LB
      controls, 1804 (93.4%) had placental examination. This is the largest prospective
      study to include population-based SB and LB, using standardized postmortem and
      placental examination, medical record review, maternal interview, collection of
      samples, and a multidisciplinary team of investigators collaborating in the
      analyses. Thus it has the potential to provide high-level evidence regarding the
      contribution of placental abnormalities to stillbirth.

PMID- 21717388
TI  - Intraluminal latex tubing for microsurgical training.

PMID- 21717389
TI  - Reconstruction of the soft tissue defects of foot and ankle with neural-island
      flaps: mono-institutional case series.
AB  - The aim of this report is to show the results obtained from using the neural
      island flap to cover the soft tissue defects of the foot and ankle. This is the
      first report of the neural-island flap series since the introduction of this flap
      to the literature in 2003. Between 2002 and 2009 "neural-island flap" was used to
      treat 20 patients of various lesions on the foot and ankle. All of the patients
      had serious soft tissue defects that compromised tendons, bones, or joints. In 16
      patients, the tissue defects were completely and successfully covered with an
      uncomplicated postoperative course. In 4 patients the flaps presented venous
      congestion and intermittent bleeding and leech application was performed for 2 to
      3 days postoperatively. Two of these flaps healed completely without any flap
      loss. In one patient because the partial flap necrosis occurred in distal one
      fourth of the flap, skin grafting was performed after 1 week of vacuum-assisted
      closure application. Total flap necrosis occurred in only one patient who was
      suffering from Buerger disease. The authors conclude that the neural-island flap
      is a highly versatile, easy, and reproducible flap that avoids the use of
      complicated and risky reconstruction options. It can be considered as an
      alternative reconstruction option particularly in problematic cases that are not
      suitable for local or free tissue transfers.

PMID- 21717390
TI  - Reconstruction of large traumatic segmental defects of the femur using segmental
      allograft with vascularized fibula inlay.
AB  - Segmental defects of the distal femur following trauma pose a reconstructive
      challenge. A stable reconstruction capable of withstanding high forces while
      allowing early mobility is paramount. The Capanna technique of reconstruction
      combining allograft with vascularized bone graft provides such a construct and
      has been described for oncological resection. We describe a modified Capanna
      technique, the "inlay" construct. Three reconstructions were performed for distal
      femoral segmental loss following trauma. One patient had bilateral
      reconstructions. Bone defects measuring 11, 9, and 8 cm were reconstructed using
      a large segmental allograft and free fibular flap inlay assembly. Both patients
      made uneventful recoveries and achieved full weight-bearing without walking aids
      6 months postreconstruction. Range of movement of each knee joint achieved at
      least 90 degrees of active flexion. We have shown that large segmental traumatic
      defects of the femur can be successfully reconstructed using segmental allograft
      with vascularized fibula inlay. This reconstruction provides early mechanical
      stability, protecting the fibula from fracturing and allowing axial loading of
      healing bone. The inlay assembly allows a large area of bony contact between
      allograft and vascularized bone, optimizing bony healing. It is a good
      alternative to other established techniques of managing significant segmental
      defects of the distal femur.

PMID- 21717391
TI  - Basic training model for supermicrosurgery: a novel practice card model.
AB  - Supermicrosurgery has been developed and reported the anastomosis of vessels with
      diameters of about 0.5 mm or less. The anastomosis of vessels of about 0.5 mm or
      less in diameter is technically more difficult than 1.0 mm or larger. This
      article describes a novel practice card model for acquiring basic
      supermicrosurgical techniques. A practice card is composed of very small-caliber
      silicone tubes simulating very small-caliber vessels and a thick paper. The
      silicone tube external diameters are 0.3, 0.5, or 0.7 mm. The thickness of the
      tube wall is 0.05 mm. Microsurgeons can easily begin to practice and warm up the
      supermicrosurgical suturing and anastomosing techniques using this nonvital
      practice card under a personal desk stereomicroscope in the office and an
      operating microscope in the operating room. This training model is a simple
      system for practicing basic supermicrosurgical techniques repeatedly and for
      warming up before a supermicrosurgical operation. This article also describes
      basic training regarding its use at high magnifications. This training-based
      supermicrosurgical skill may become a valuable technique for microsurgeons in
      many specialties.

PMID- 21717392
TI  - The application of indocyanine green fluorescence angiography in plastic surgery.
AB  - In flap reconstruction of complex defects the perfusion of the reconstructive
      flap is critical to the ultimate success of the reconstruction. This is
      especially true in perforator-based flaps where it can be difficult to assess the
      adequacy of perfusion in the operating room. However, the ability to definitively
      determine the degree of flap perfusion is imperative to clinical decision-making.
      An emerging technology using near-infrared angiography with indocyanine green
      (ICG) dye may significantly improve the immediacy and accuracy of the assessment
      of flap perfusion. This article reviews the current state of ICG angiography and
      its use in clinical practice in plastic surgery. There are 17 case series,
      including a total of 386 patients, published in the literature using ICG
      angiography in various plastic surgical procedures. ICG angiography may aid flap
      design and assessment in the intraoperative/postoperative settings, reduce
      complications, and ultimately improve outcomes.

PMID- 21717393
TI  - The influence of pedicle tension and twist on perforator flap viability in rats.
AB  - When a perforator flap is transposed in pedicled fashion, twisting, tension, or
      both can be inflicted on the pedicle. Although high density twisting undoubtedly
      decreases flap survival, the effect of pedicle tension with or without twisting
      has not been studied for perforator flaps. The authors designed a model of
      nonanastomotic pedicle tension using a cranial epigastric perforator flap in
      rats. Sprague-Dawley rats were divided into 4 groups-control, twist, tension,
      tension plus twist groups; each group consists of 10 rats. Tension group had
      lower flap survival ratios than control and the flap survival ratio of tension
      plus twist group was lower than those of the other groups ( P < 0.05). Pedicle
      tension was found to decrease perforator flap survival and its detrimental effect
      was exacerbated by twisting. Surgeons need to have a lower threshold for
      correction of pedicle tension when twisting is combined than without a twist.

PMID- 21717394
TI  - Case of combined thenar and hypothenar hammer syndrome: case report and brief
      review of the literature.
AB  - Acute or chronic arterial thrombose due to repetitive blunt trauma to the palm of
      the hand is a rare occupational vascular disease. In most of the cases it affects
      the ulnar artery and its superficial palmar branch. Repetitive crush is
      pathogenic and the unique anatomy of the superficial branch of the ulnar artery
      lying next to the hook of hamate is causative. In rare cases it may affect the
      superficial palmar branch of the radial artery, called thenar hammer syndrome.
      The combination of both is an absolute rarity. Both syndromes are occupational
      diseases in workers using the hand as a hammer. Patients typically present with
      Raynaud phenomenon or complain about ischemic pain, cold intolerance, or
      cyanosis. The gold standard in diagnosis is the angiography. Surgical or
      conservative treatment can be performed successfully. We present a case of
      combined thenar and hypothenar hammer and a brief review of the literature.

PMID- 21717395
TI  - "Babysitting" the flap: a novel approach to chimeric flap transfer.
AB  - Previous studies have described compound flaps based on the subscapular system
      for a variety of reconstructive needs. Most commonly, the combination includes
      the fasciocutaneous parascapular flap with the latissimus dorsi muscle flap used
      in the reconstruction of extensive lower extremity wounds. Indications for
      combined flaps are typically restricted to selective and complex reconstructions.
      Our experience with a novel approach to compound flap transfer in an elderly
      patient with multiple comorbidities is described.

PMID- 21717396
TI  - The effects of hypotension and norepinephrine on microvascular flap perfusion.
AB  - Microvascular flap surgery is a common technique in reconstructive surgery. The
      wide indications and variable patients provide challenge also for
      anesthesiologist. Both hypotension and hypoperfusion can be harmful to the flap.
      Hypotensive patients are treated with fluid resuscitation and vasopressors (e.g.,
      norepinephrine), if needed. As vasoconstrictors, vasopressors might impair
      microvascular flap perfusion. In this experimental pig model we studied the
      effect of sevoflurane-induced hypotension on the perfusion of microvascular and
      superiorly pedicled rectus abdominis myocutaneous flaps. In addition, we
      evaluated the effect of norepinephrine on flap perfusion when it was used for
      correction of hypotension. Microdialysis (MD) was used to detect metabolic
      changes, as it is a sensitive method to detect early changes of tissue metabolism
      and ischemia in different tissue components of soft tissue flaps. The main
      finding of this study was that moderate degree of normovolemic hypotension or the
      use of norepinephrine for the correction of this hypotension did not affect flap
      perfusion as assessed by MD. More studies are clearly needed to confirm the
      safety of norepinephrine in clinical use in microsurgery.

PMID- 21717397
TI  - Immediate microsurgical breast reconstruction and simultaneous sentinel lymph
      node dissection: issues with node positivity and recipient vessel selection.
AB  - Sentinel lymph node dissection (SLND) during mastectomy has been increasing given
      the decreased risk of lymphedema. Simultaneous reconstruction with a
      microsurgical breast reconstruction is often performed, but with node positivity
      a completion axillary lymph node dissection (ALND) must be performed
      subsequently. This study examines the potential risks especially in relation to
      microsurgical reconstruction. All patients undergoing microsurgical breast
      reconstruction at an academic institution from 2004 to 2010 were evaluated in a
      prospective database. Patients with immediate reconstruction and SLND were
      identified. Management of positive lymph node status was ascertained through
      extensive chart review. There were 610 reconstructions performed, 170 delayed and
      440 immediate. From the immediate reconstructions, 110 patients (25%) had SLND
      and of these patients, 16 (14.55%) had a positive SLND. All 16 patients had
      internal mammary recipient vessels for free tissue transfer. Seven patients had
      intraoperative completion ALND, while nine patients had staged completion ALND at
      a later date. There were no adverse affects from completion ALND. Simultaneous
      mastectomy, SLND, and microsurgical reconstruction can be performed safely. The
      internal mammary vessels are preferred recipient vessels as node positive
      patients may require subsequent completion ALND. If a thoracodorsal anastomosis
      is performed, a potential risk exists for vessel injury and flap loss with
      completion ALND.

PMID- 21717398
TI  - The use of visible light spectroscopy to measure tissue oxygenation in free flap
      reconstruction.
AB  - The loss of a free flap is a feared complication for both the surgeon and the
      patient. Early recognition of vascular compromise has been shown to provide the
      best chance for flap salvage. The ideal monitoring technique for perioperative
      free flap ischemia would be noninvasive, continuous, and reliable. Visible light
      spectroscopy (VLS) was evaluated as a new method for predicting ischemia in
      microvascular cutaneous soft tissue free flaps. In an Institutional Review Board
      approved prospective trial, 12 patients were monitored after free flap
      reconstructions. The tissue hemoglobin oxygen saturation (StO (2)) and total
      hemoglobin concentration (THB) of 12 flaps were continuously monitored using VLS
      for 72 hours postoperatively. Out of these 12 flaps 11 were transplanted
      successfully and 1 flap loss occurred. The StO (2 )was 48.99% and the THB was
      46.74% for the 12 flaps. There was no significant difference in these values
      among the flaps. For the single flap loss, the device accurately reflected the
      ischemic drop in StO (2) indicating drastic tissue ischemia at 6 hours
      postoperatively before the disappearance of implantable Doppler signals or
      clinical signs of flap compromise. VLS, a continuous, noninvasive, and localized
      method to monitor oxygenation, appeared to predict early ischemic complications
      after free flap reconstruction.

PMID- 21717399
TI  - Limb transplantation and targeted reinnervation: a practical comparison.
AB  - Limb transplantation and targeted reinnervation are complimentary but very
      different approaches for restoring function to an upper limb amputee. This
      article reviews the advantages and limitations of both of these procedures, and
      highlights the reconstructive obstacles in the treatment of upper limb amputees.

PMID- 21717400
TI  - [How accurate is the correlation between clinical and pathological TNM stages in
      renal tumours?].
AB  - PURPOSE: In clinical practice the tumour size measured in the histopathological
      examination of the operative specimen is used both to determine tumour stage. We
      have investigated the agreement between tumour size determined by preoperative
      computed tomography (CT) and pathological tumour size. MATERIAL AND METHODS:
      Between 2000 and 2007 a total of 444 consecutive patients was diagnosed with a
      renal tumour and treated operatively at our clinic. A total of 276 patients was
      eligible and thus included in the study. RESULTS: There were 62% men and 38%
      women with a median age of 65 years. There were 255 renal cell carcinomas, 7
      oncocytomas, 3 angiomyolipomas, and 11 tumours of other histology. Mean tumour
      size was 65 mm in preoperative radiographic estimates and thereby a mean of 3 mm
      smaller than the mean pathological tumour size (62 mm, p = 0.0000066). In the
      radiographic estimate only 67% of the tumours were in the range of a 1 cm size
      difference of the postoperatively determined tumour size and in only 53% of the
      cases did the clinical and pathological TNM stages match. In 28/276 cases (10%)
      the clinical tumour stage was >= T2 but the histopathological examination showed
      a pTNM stage < T2. CONCLUSIONS: Different tomographs as well as observers are
      probably the main causes for the present results. Standardisation should be
      established to provide an accurate basis for a differentiated discussion about
      therapeutic options. This is especially true for low tumour stages where tumour
      size is the only criterion for staging.

PMID- 21717401
TI  - [From the Expert Office: Can "Goasslschnalzen" (a bavarian tradition using whips)
      cause an acoustic shock?].

PMID- 21717402
TI  - Graves' ophthalmopathy in patients treated with radioiodine 131-I.
AB  - BACKGROUND: Radioiodine treatment of hyperthyroidism in Graves' disease patients
      may cause or aggravate the course of ophthalmopathy (GO). We evaluated the
      activity and severity of ophthalmopathy in patients who acquired GO following
      radioiodine therapy. MATERIAL AND METHODS: Between 2003 and 2005, 763 Graves'
      disease patients (50.9% of the total number of 1,500 patients referred to our
      Department) were treated with radioiodine 131-I. This treatment was only offered
      to patients with NOSPECS score < 3 and CAS < 3. Following their radioiodine
      treatment, in 39 patients (5.1% of all Graves' disease patients), mean age 53.9
      +/- 11.6 years, onset of GO was observed within 12 months of post-treatment
      follow-up. RESULTS: In 39 patients who developed GO after 131-I treatment, median
      values of hTRAb and NOSPECS score were 15.4 U/L (IQR = 22.9) and 5.0 points (max
      = 8.0; min = 2.0), respectively, at the time of their GO onset. Patients were
      qualified for methylprednisolone pulse therapy (8.0 g) and subsequent
      radiotherapy (20 Gy). Median concentration of hTRAb and NOSPECS score at one, six
      and 12 months post-GO therapy were: 10.0 U/L (IQR = 21.6) and 4.0 (max = 6.0; min
      = 1.0); 7.5 U/L (IQR = 1.1) and 3.0 (max = 10.0; min = 0.0); 2.8 U/L (IQR = 8.3)
      and 3.0 (max = 6.0; min = 0.0), respectively. A positive association between
      hTRAb and NOSPECS score was observed over the control period. IL-6 and IL-2
      concentration prior to and one month after treatment remained elevated.
      CONCLUSIONS: Since 5% of our Graves' disease patients developed severe GO
      following radioiodine treatment, an association between radioiodine therapy and
      severe ophthalmopathy cannot be excluded. IL-6 and IL-2 concentrations remained
      elevated after glucocorticoid therapy.

PMID- 21717403
TI  - Elements of oxidation/reduction balance in experimental hypothyroidism.
AB  - BACKGROUND: The aim of this study was to investigate the effect of the decreased
      level of thyroid hormones on selected parameters of the oxidation/reduction
      balance by assessing the activity of antioxidant enzymes: superoxide dismutase
      (SOD), and glutathione peroxidase (GSH-Px); the level of antioxidant vitamins (A,
      C, and E); and the concentration of compounds reacting with thiobarbituric acid
      (TBARS). MATERIAL AND METHODS: Investigations involved 20 Belgian giant rabbits
      of both sexes. Hypothyroidism was induced by intragastric administration of
      thiamizole. Before this was done, blood was collected from the ear marginal vein
      (control group) and then the animals received thiamizole through an intragastric
      tube at a dose of 2 mg/kg b.w. for 21 days. Blood was collected again (the
      experimental group) and the following determinations were performed: - in blood
      serum, the thyroid hormones T3, T4 and TSH; - vitamin A, C and E blood serum
      concentrations; - in erythrocytes, the concentration of compounds reacting with
      TBARS, SOD and GSH-Px. RESULTS: A 21-day exposure of rabbits to thiamazole (2
      mg/kg b.w./24 h) resulted in a statistically significant decrease of TBARS, a
      decrease of SOD and GPH-Px activity and in a statistically insignificant decrease
      in the level of vitamins A, C and E. CONCLUSIONS: Hypothyroidism decreases the
      level of erythrocytes oxidation/reduction balance by diminishing oxidative lipids
      damage and by decreasing the activity of antioxidative enzymes, but not by
      changes in the level of antioxidant vitamins.

PMID- 21717404
TI  - Large deletion in the KAL1 gene in two related patients with hypogonadotropic
      hypogonadism: diagnostic usefulness of cytogenetic and molecular methods.
AB  - BACKGROUND: Kallmann syndrome type 1 (KS1) is a heterogeneous disorder where
      hypogonadotropic hypogonadism (HH) associated with an impaired sense of smell is
      observed. The aim of this study was to investigate the usefulness of the
      multiplex ligation-dependent probe amplification (MLPA) technique for
      differential diagnosis in comparison with molecular cytogenetics - fluorescence
      in situ hybridisation (FISH) or traditional PCR analysis and propose a diagnostic
      approach for patients with KS. MATERIAL AND METHODS: Karyotype and PCR analysis
      in two related patients and other family members were performed, followed by MLPA
      dosage sensitive analysis. RESULTS: In the proband and his maternal uncle, the
      PCR allowed the detection of a large deletion within the KAL1 gene, from exon 4
      to 14 (c.469-?_6314+?del). The deletion was also diagnosed in three female
      carriers in the presented family. These results were proved by the MLPA
      technique. Moreover, we traced the presence of the region located downstream and
      upstream to the KAL1 gene on Xq22.32. However, FISH analysis failed to reveal any
      deletion in the critical region for KS. Simultaneously, we report difficulties
      connected with the PCR technique based on the primers for KAL1 amplification
      presented in the literature. We designed primers that are specific to the X
      chromosome and bypass pseudogene KALY amplification. CONCLUSIONS: FISH analysis
      is a convenient screening technique, but in the presented family it failed to
      detect the deletion. Therefore, in the face of a distinctive manifestation of KS,
      a subsequent molecular assay should be introduced. The MLPA is a useful technique
      for differential diagnosis in patients with HH combined with smell impairment.

PMID- 21717405
TI  - Clinical observations and hormone screenings of patients with non-standard
      hypertrophy of the adrenal cortex.
AB  - BACKGROUND: Non-standard hypertrophy of the adrenal cortex is a rare
      endocrinopathy causing the incidence of hyperandrogenism among women of
      procreative age. The primary objective of this paper is the specification of the
      clinical picture and modifications of the concentration of pituitary, ovarian and
      adrenal hormones in the blood of female patients with the syndrome of non
      standard hypertrophy of the adrenal cortex (NPKN). MATERIAL AND METHODS: In the
      Gynaecological Endocrinology Clinic of the Silesian Medical University in
      Katowice, Poland, 2,353 female patients were hospitalised between 1 January 2003
      and 30 June 2009 with symptoms of hyperandrogenism. Of these, 55 were selected
      for the study. Eventually, 25 female patients with diagnosed NPKN, and 30
      randomly selected patients with the polycystic ovarian disease polycystic ovary
      syndrome (PCOS) were enrolled in the study. RESULTS: Of the 2,353 female patients
      hospitalised in the Gynaecological Endocrinology Clinic with symptoms of
      hyperandrogenism between 1 January 2003 and 30 June 2009, NPKN was found in 1.2%
      of them. Patients with NPKN displayed a strong hirsutism, which was significantly
      more intense than in the comparative group. Insulin resistance was found more
      frequently in the group of female patients with PCOS (67%) compared to the group
      with NPKN (40%). Polycystic ovarian disease was more frequently observed in the
      group of patients with PCOS (93%), compared to the group with NPKN (72%). The
      average concentration of androstendione in the blood serum in the group of
      patients with NPKN amounted to 7.60 ng/ml (SD = 3.57) and was significantly
      higher than in the group of patients with PCOS where it was 3.46 ng/ml (SD =
      1.53). The average concentration of free testosterone in the blood serum in the
      group of patients with NPKN amounted to 7.30 pg/ml (SD = 4.13) and was
      significantly higher than in the group of patients with PCOS, where it was 2.90
      pg/ml (SD =1.43 ). The average concentration of DHEAS in the blood serum in the
      group of patients with NPKN accounted for 403.23 MUg/dl (SD = 192.59), and in the
      group with PCOS it was 257.39 MUg/dl (SD = 63.67). This concentration was
      statistically significantly higher in the group with NPKN than in the group with
      PCOS. The average concentration of estradiole in the blood serum in the group
      with NPKN amounted to 111.98 pg/ml (SD = 113.68), while in the group with PCOS it
      was 62.39 pg/ml (SD = 31.18). The difference of concentrations between the groups
      NPKN and PCOS was statistically significant. We found a positive correlation
      between the 17-OHP concentration after 60 minutes of the ACTH test and the
      severity of hirsutism in the group of patients with NPKN (r = 0.77896). In
      addition, we found a correlation between the free testosterone and the 17-OHP
      concentration after 60 minutes of the ACTH test in the group of patients with
      NPKN (r = 0.48149). A positive correlation was also reported between the symptom
      of hypertrophy of the clitoris and the 17-OHP concentration after 60 minutes of
      the ACTH stimulation test in the group of patients with NPKN (r = 0.77221). In
      the comparative group of patients with PCOS, there was no correlation between the
      free testosterone and 17-OHP concentration after 60 minutes of the ACTH test (r =
      0.3059). There was also no correlation between the severity of hirsutism and the
      concentration of 17-OHP concentration analysed after 60 minutes of the ACTH test.
      In all female patients from the PCOS group, there was a correct size of clitoris.
      CONCLUSIONS: Analysing the clinical picture of the examined population of
      patients with NPKN enabled us to specify symptoms of disease which were
      significant for diagnosis, and which helped differentiate NPKN from other
      endocrinopathies involving hyperandrogenism, including in particular PCOS. Taking
      everything into consideration, non-standard hypertrophy of the adrenal cortex is
      a rare cause of hyperandrogenism in women of procreative age. Intense hirsutism
      and features of virilisation presenting as hypertrophy of the clitoris
      predominate in the clinical picture of non-standard hypertrophy of the adrenal
      cortex. The laboratory confirmation of diagnosis of NPKN constitutes the analysis
      of the 17-OHP level in blood in the ACTH stimulation test. The analyses of free
      testosterone and its unbound fraction, androstendione and estradiole, help
      differentiate NPKN from polycystic ovarian disease.

PMID- 21717406
TI  - The prevalence of polycystic ovary syndrome in Iranian women based on different
      diagnostic criteria.
AB  - BACKGROUND: This study aimed to determine the prevalence of polycystic ovary
      syndrome (PCOS) in Iranian women based on different diagnostic criteria. MATERIAL
      AND METHODS: This cross-sectional study was conducted in 2009 in Isfahan, Iran
      among females referred to the mandatory pre-marriage screening clinic. Menstrual
      irregularity was assessed as the presence of chronic amenorrhea or a menstrual
      cycle length of less than 21 days or more than 35 days, or more than four days of
      variation between cycles. Clinical hyperandrogenism was assessed as the self
      reported degree of hirsutism using the modified Ferriman Gallwey (mF-G) scoring
      method based on a chart displaying degree of hair growth in nine regions. Those
      participants who reported menstrual irregularity and/or who had an mF-G score of
      >= 8 were invited for a clinical examination. Those who did not have these
      criteria were not further evaluated and were deemed not to have PCOS.
      Participants with abnormal findings underwent blood test and abdominal sonography
      of their ovaries. In those with hirsutism, serum was obtained on the 22(nd)
      24(th) day of the cycle for the measurement of progesterone; free testosterone
      was measured in those with menstrual irregularity. RESULTS: The estimated
      prevalence of PCOS was 7% based on the NIH criteria, 15.2% under the Rotterdam
      criteria, and 7.92% according to the AES criteria. CONCLUSION: The Rotterdam
      prevalence estimates were double those obtained with the NIH criteria. This study
      can be used for international comparisons because it was conducted on a
      representative sample of females using different criteria for the definition of
      PCOS.

PMID- 21717407
TI  - Selected markers of endothelial dysfunction in women with polycystic ovary
      syndrome.
AB  - BACKGROUND: The increased incidence of cardiovascular disease in women with
      polycystic ovary syndrome (PCOS) has prompted researchers to look for indicators
      of early atherosclerotic changes in these patients. One of the earliest stages of
      atherogenesis is endothelial cell dysfunction. The aim of this study was to
      assess the levels of selected plasma markers of endothelial injury [E-selectin,
      endothelin-1 (ET-1) and von Willebrand Factor antigen (vWF:Ag)] in PCOS women
      before and after six months of treatment. MATERIAL AND METHODS: 32 patients with
      PCOS aged 18-36 years (mean age 25.16 +/- 5.80) were included in the study. The
      control group consisted of 20 healthy women matched for age and body mass. The
      levels of ET-1, vWF:Ag, E-selectin, fasting glucose, insulin, total cholesterol,
      HDL and LDL-cholesterol and triglycerides were assessed. In the PCOS group, all
      these tests were repeated after six months of treatment. RESULTS: The study
      showed higher levels of vWF:Ag (p = 0.043), E selectin (p = 0.028), insulin (p =
      0.044), glucose (p = 0.036) and LDL (p = 0.006) in PCOS patients versus healthy
      women. A positive correlation was demonstrated between E selectin and glucose (p
      = 0.0001), triglycerides (p = 0.014) and uric acid (p = 0.008). vWF:Ag levels
      showed a positive correlation with glucose (p = 0.04) and triglycerides (p =
      0.036). A positive correlation was also found between ET-1 and total cholesterol
      levels (p = 0.012) in PCOS women. After treatment, there was a significant
      reduction in E-selectin levels from baseline (p = 0.002) and an increase in the
      levels of HDL (p = 0.0002) and triglycerides (p = 0.033). CONCLUSIONS: Elevated
      levels of vWF:Ag and E selectin in PCOS women suggest endothelial dysfunction in
      this group of patients. Glucose and triglyceride are significant factors
      affecting endothelial function in PCOS.

PMID- 21717408
TI  - Vitamin D deficiency prevalence in summer compared to winter in a city with high
      humidity and a sultry climate.
AB  - BACKGROUND: Vitamin D deficiency is high in winter because of reduced exposure to
      sunlight. It seems that in places with high humidity and a sultry climate,
      exposure to sunlight in summer can be low too. This study was designed to
      determine the vitamin D deficiency prevalence in Sari, a city with a high
      humidity climate at the end of summer, and compare it to winter. MATERIAL AND
      METHODS: This cross-sectional study was carried out on men and women aged 10 to
      70. Clustered blood samples were received from 351 subjects who participated in
      this study toward the end of summer, and in winter. The levels of serum vitamin
      D, calcium, phosphorus, alkaline phosphatase and PTH were measured. T test and X2
      were used for data analysis. RESULTS: 351 subjects (66.4% women, 33.6% men) aged
      11 to 69 (mean age +/- SD 37.11 +/- 12.6) participated in the study. The mean 25
      (OH) D concentration in summer was 13.41 +/- 13, and in winter it was 11.7 +/-
      11, and the difference was statistically significant (p < 0.02). The prevalence
      of 25-OHvitamin D deficiency was 87.5% (307) in winter and 78.6% (276) in summer
      (p < 0.05). CONCLUSION: This study shows that although in this area with a high
      humidity climate, seasonal variation of vitamin D is statistically significant,
      the prevalence of Vitamin D insufficiency is as high in summer as in winter.

PMID- 21717409
TI  - Interactive effects of melatonin, exercise and diabetes on liver glycogen levels.
AB  - BACKGROUND: This study aimed to examine the effects of melatonin supplementation
      on liver glycogen levels in rats with streptozotocin- induced diabetes and
      subjected to acute swimming exercise. MATERIAL AND METHODS: Eighty Sprague-Dawley
      type adult male rats were divided into eight groups: Group 1, general control;
      Group 2, melatonin-supplemented control; Group 3, melatonin-supplemented
      diabetes; Group 4, swimming control; Group 5, melatonin-supplemented swimming;
      Group 6, melatonin-supplemented diabetic swimming; Group 7, diabetic swimming;
      Group 8, diabetic control. Melatonin was supplemented at a dose of 3 mg/kg/day
      intraperitoneally for four weeks. Liver tissue samples were collected and
      evaluated using a Nikon Eclipse E400 light microscope. All images obtained from
      the light microscope were transferred to PC medium and evaluated using Clemex PE
      3.5 image analysis software. RESULTS: The lowest liver glycogen levels in the
      study were found in group 4. Liver glycogen levels in groups 3, 6, 7 and 8 (the
      diabetic groups) were higher than group 4, but lower than those in groups 1 and
      2. The lowest liver glycogen levels were obtained in groups 1 and 2. CONCLUSIONS:
      The study indicates that melatonin supplementation maintains the liver glycogen
      levels that decrease in acute swimming exercise, while induced diabetes prevents
      this maintenance effect in rats.

PMID- 21717410
TI  - The role of leptin in the regulation of carbohydrate metabolism.
AB  - The hormone leptin is secreted from white adipocytes, and serum levels of leptin
      correlate with adipose tissue mass. Leptin was first described as acting on the
      satiety centre in the hypothalamus through specific receptors (ob-R) to restrict
      food intake and enhance energy expenditure. Leptin plays a crucial role in the
      maintenance of body weight and glucose homeostasis hrough central and peripheral
      pathways, including regulation of insulin secretion by pancreatic b cells. Leptin
      may also directly affect the metabolism and function of peripheral tissues.
      Leptin has been implicated in causing peripheral insulin resistance by
      attenuating insulin action, and perhaps insulin signalling, in various insulin
      responsive cell types. Research has demonstrated a significant relationship
      between leptin and insulin, but the mechanisms underlying the changes of leptin
      induced by insulin, and vice versa, remain to be studied in more detail. Recent
      data provides convincing evidence that leptin has beneficial effects on glucose
      homeostasis in mouse models of insulin-deficient type 1 diabetes mellitus. Our
      study suggests that leptin could be used as an adjunct of insulin therapy in
      insulin-deficient diabetes, thereby providing an insight into the therapeutic
      properties of leptin as an anti-diabetic agent. Safety evaluation should include
      a careful assessment of the effects of this combination therapy on the
      counterregulatory response to hypoglycaemia. The role of leptin in alpha-cell
      function has not been studied in detail. Extensive studies will be needed to
      determine the long-term safety and efficacy of this therapy.

PMID- 21717411
TI  - Hypogonadotropic hypogonadism due to GnRH receptor mutation in a sibling.
AB  - Hypogonadotropic hypogonadism (HH) is characterised by delayed puberty and
      infertility. Congenital HH comprises Kallmann syndrome with hypo-/anosmia and
      idiopathic HH (IHH). The genetic origin remains unknown in most cases, but the
      defective GnRH receptor gene (GNRHR) accounts for a considerable proportion of
      IHH. Here we describe a pair of siblings diagnosed with IHH. Aged 17 years, the
      boy was referred because of short stature (162 cm) and overweight (62.5 kg). He
      presented no signs of puberty, bone age of 14.5 years and insulin resistance. His
      sister, aged 16 years, also displayed delayed puberty. She was 166 cm tall and
      weighed 52 kg; her bone age was 12.5 years. Pelvic ultrasonography showed an
      infantile uterus and fibrous ovaries. In both siblings, serum gonadotropins were
      extremely low, and non-responsive to GnRH. Testosterone (1.38 nmol/l) and IGF1
      (273 ng/ml) were decreased in the boy, although the girl did not present IFG1
      deficiency. Her serum oestradiol was 10 pg/ml. MRIs of the hypothalamo-pituitary
      region and olfactory bulbs revealed them to be normal. The patients' sense of
      smell was unaltered. Their parents appeared to be first degree cousins.
      Considering the clinical data and potentially autosomal recessive HH
      transmission, the GNRHR gene was screened. The siblings turned out to be
      homozygous for the G416A transition, which had previously been identified in
      other HH individuals. The parents were heterozygous mutation carriers. The
      proband, moderately responding to LH, was started on low dose testosterone
      replacement, and his sister on transdermal oestradiol. Molecular data indicative
      of GnRH resistance could guide their future therapy should they desire fertility
      restoration. Further observations of the male patient may provide insights into
      androgen's influence on body mass, growth and insulin sensitivity.

PMID- 21717412
TI  - Primary pigmented nodular adrenocortical disease.
AB  - Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenal tumour
      causing corticotrophin-independent Cushing's syndrome. It occurs mainly in
      children and young adults. The histological examination is characterised by small
      pigmented micronodules on the adrenal cortex. The diagnosis is most often seen in
      patients with Carney Complex, but it can also occur in isolation. We report a
      case of Carney Complex that was referred for adrenalectomy. The procedure was
      uneventful and the patient was well at discharge. The adrenal pathology showed
      numerous black nodules measuring less than 2mm in diameter. This feature was
      pathognomonic of primary pigmented nodular adrenocortical disease.

PMID- 21717413
TI  - Effectiveness of chronic treatment with ketoconazole in a patient with diabetic
      Cushing's disease resistant to surgery.
AB  - Without treatment, Cushing's disease has significant morbidity and mortality.
      Where a surgical approach may not be feasible, or is refused by the patient,
      medical therapy becomes the only option. In this case report, we discuss the
      effects of two years of ketoconazole treatment on diabetes regulation and insulin
      resistance in a patient reluctant to agree to surgery. A 62 year-old female
      patient with uncontrolled type 2 diabetes mellitus was investigated. Cushing's
      disease was confirmed by the results of high urine free cortisol level and
      dexamethasone suppression tests. We discuss the effects of two years of 600
      mg/day ketoconazole treatment on diabetes regulation and insulin resistance in a
      patient with Cushing's disease reluctant to agree to surgery. This case report
      illustrates the beneficial long-term effects of 24 months of ketoconazole
      treatment on the clinical and laboratory findings and also on steroid and glucose
      metabolism.

PMID- 21717414
TI  - The dawn phenomenon and the Somogyi effect - two phenomena of morning
      hyperglycaemia.
AB  - Morning hyperglycaemia in diabetic subjects may be caused by the dawn phenomenon,
      or the Somogyi effect, or poor glycaemic control. The dawn phenomenon occurs when
      endogenous insulin secretion decreases or when the effect of the exogenous
      insulin administered to the patient the day before disappears, together with a
      physiological increase in insulin-antagonistic hormones. The Somogyi effect is
      present in the case of excessive amounts of exogenous insulin. The dawn
      phenomenon is more common than the Somogyi effect. To diagnose these phenomena,
      it is useful to measure plasma glucose levels for several nights between 3 a.m.
      and 5 a.m. or use a continuous glucose monitoring system. Although their
      treatment differs, the best way of preventing both the dawn phenomenon and the
      Somogyi effect is an optimal diabetes control with insulin therapy.

PMID- 21717415
TI  - Hyperbaric oxygen therapy in diabetic patients - comments on the paper by
      Karadurmus et al.

PMID- 21717419
TI  - Intersecting roads to rheumatoid arthritis.

PMID- 21717420
TI  - NF-AT5 is a critical regulator of inflammatory arthritis.
AB  - OBJECTIVE: To investigate the role of NF-AT5, an osmoprotective transcription
      factor, in synovial hyperplasia and angiogenesis in patients with rheumatoid
      arthritis (RA). METHODS: The expression of NF-AT5 in synovial tissue and
      synoviocytes from RA patients was examined by immunohistochemistry and Western
      blot analysis, respectively. Messenger RNA (mRNA) in RA synoviocytes and human
      umbilical vein endothelial cells (HUVECs) transfected with dummy small
      interfering RNA (siRNA) or NF-AT5 siRNA were profiled using microarray
      technology. Assays to determine synoviocyte apoptosis and proliferation were
      performed in the presence of NF-AT5 siRNA. VEGF165-induced angiogenesis was
      assessed by measuring the proliferation, tube formation, and wound migration of
      HUVECs. Experimental arthritis was induced in mice by injection of anti-type II
      collagen antibody. RESULTS: NF-AT5 was highly expressed in rheumatoid synovium,
      and its activity was increased by proinflammatory cytokines, such as interleukin
      1beta and tumor necrosis factor alpha. The mRNA profiling of synoviocytes and
      HUVECs transfected with NF-AT5-targeted siRNA revealed 3 major changes in
      cellular processes associated with the pathogenesis of RA: cell cycle and
      survival, angiogenesis, and cell migration. Consistent with these results, NF-AT5
      knockdown in RA synoviocytes and HUVECs inhibited their proliferation/survival
      and impeded angiogenic processes in HUVECs. Mice with NF-AT5 haploinsufficiency
      (NF-AT5(+/-)) developed a very limited degree of synovial proliferation, as seen
      on histologic analysis, and decreased angiogenesis, and they exhibited a nearly
      complete suppression of experimentally induced arthritis. CONCLUSION: NF-AT5
      regulates synovial proliferation and angiogenesis in chronic arthritis.

PMID- 21717421
TI  - Increased interleukin-1beta gene expression in peripheral blood leukocytes is
      associated with increased pain and predicts risk for progression of symptomatic
      knee osteoarthritis.
AB  - OBJECTIVE: To evaluate whether gene expression profiles could serve as biomarkers
      of symptomatic knee osteoarthritis (OA) by examining gene expression profiles in
      peripheral blood leukocytes (PBLs) from patients with OA compared with those from
      non-OA controls, and to determine whether candidate genomic biomarkers (PBL
      expression of inflammatory genes) predict an increased risk of disease
      progression in patients with symptomatic radiographic knee OA. METHODS: Three
      independent cohorts of patients with knee OA and non-OA control subjects were
      studied. Two cohorts (a learning cohort and a validation cohort) were recruited
      at New York University Hospital for Joint Diseases (NYUHJD), and 1 cohort (a
      validation cohort) was recruited at Duke University Medical Center. PBL gene
      expression was assessed using Affymetrix microarray and was confirmed by
      quantitative polymerase chain reaction (qPCR). Radiographic progression at 2
      years was assessed in 86 patients. RESULTS: We identified 173 genes that were
      significantly up-regulated or down-regulated (>=1.5-fold change) in OA PBLs, at a
      false discovery rate of 5%. Cluster analysis revealed 2 distinct subgroups among
      the patients with OA: those in whom the expression of interleukin-1beta (IL
      1beta) was increased >=2-fold compared with controls, and those in whom the
      expression of IL-1beta was comparable with that in controls. Overexpression of IL
      1beta in these OA subclasses was validated using qPCR in all 3 cohorts. Patients
      with the inflammatory "IL-1beta signature" had higher pain scores and decreased
      function and were at higher risk of radiographic progression of OA. CONCLUSION:
      PBLs from patients with symptomatic knee OA display a characteristic
      transcriptome profile. Moreover, increased expression of IL-1beta identifies a
      subset of patients with OA who have increased pain and are at higher risk of
      radiographic progression of OA.

PMID- 21717422
TI  - Incidence of physician-diagnosed osteoarthritis among active duty United States
      military service members.
AB  - OBJECTIVE: To examine the incidence of osteoarthritis and the influence of
      demographic and occupational factors associated with this condition among active
      duty US service members between 1999 and 2008. METHODS: To determine the total
      number of incident cases of osteoarthritis, the Defense Medical Surveillance
      System (DMSS) was queried by sex, race, age, branch of military service, and rank
      using code 715 of the International Classification of Diseases, Ninth Revision,
      Clinical Modification. Multivariable Poisson regression analysis was used to
      estimate incidence rates, rate ratios, and 95% confidence intervals (95% CIs) for
      osteoarthritis per 1,000 person-years. RESULTS: A total of 108,266 incident cases
      of osteoarthritis were documented in the DMSS within a population that
      experienced 13,768,885 person-years at risk of disease during the study period.
      The overall unadjusted incidence rate among all active duty US service members
      during the study period was 7.86 cases per 1,000 person-years. Significant
      demographic and occupational risk factors for osteoarthritis included sex, age,
      race, branch of service, and rank (P<0.001). Women experienced an adjusted
      incidence rate for osteoarthritis that was nearly 20% higher than that for men
      (rate ratio 1.19 [95% CI 1.17-1.21]). Service members ages>=40 years experienced
      an adjusted incidence rate for osteoarthritis that was ~19 times higher than that
      for those ages<20 years (rate ratio 18.61 [95% CI 17.57-19.57]). Black service
      members experienced significantly higher incidence rates of osteoarthritis than
      those in the white and "other" race categories. CONCLUSION: Rates of
      osteoarthritis were significantly higher in military populations than in
      comparable age groups in the general population.

PMID- 21717423
TI  - Improving outcome for patients with pancreatic cancer through centralization.
AB  - BACKGROUND: High-volume institutions are associated with improved clinical
      outcomes for pancreatic cancer. This study investigated the impact of
      centralizing pancreatic cancer surgery in the south of the Netherlands. METHODS:
      All patients diagnosed in the Eindhoven Cancer Registry area in 1995-2000
      (precentralization) and 2005-2008 (implementation of centralization agreements)
      with primary cancer of the pancreatic head, extrahepatic bile ducts, ampulla of
      Vater or duodenum were included. Resection rates, in-hospital mortality, 2-year
      survival and changes in treatment patterns were analysed. Multivariable
      regression analyses were used to identify independent risk factors for death.
      RESULTS: Some 2129 patients were identified. Resection rates increased from 19.0
      to 30.0 per cent (P < 0.001). The number of hospitals performing resections
      decreased from eight to three, and the annual number of resections per hospital
      increased from two to 16. The in-hospital mortality rate dropped from 24.4 to 3.6
      per cent (P < 0.001) and was zero in 2008. The 2-year survival rate after surgery
      increased from 38.1 to 49.4 per cent (P = 0.001), and the rate irrespective of
      treatment increased from 10.3 to 16.0 per cent (P < 0.001). There was no
      improvement in 2-year survival in non-operated patients. After adjustment for
      relevant patient and tumour factors, those undergoing surgery more recently had a
      lower risk of death (hazard ratio 0.70, 95 per cent confidence interval 0.51 to
      0.97). Changes in surgical patterns seemed largely to explain the improvements.
      CONCLUSION: High-quality care can be achieved in regional hospitals through
      collaboration. Centralization should no longer be regarded as a threat by general
      hospitals but as a chance to improve outcomes in pancreatic cancer.

PMID- 21717424
TI  - Comparison of open and laparoscopic live donor left lateral sectionectomy.
AB  - BACKGROUND: The present study was undertaken to determine whether laparoscopic
      live donor left lateral sectionectomy (LLS) in paediatric liver transplantation
      is a feasible, safe and reproducible procedure, compared with open live donor
      left lateral sectionectomy (OLS). METHODS: A retrospective review was conducted
      of all consecutive live donor procedures for paediatric liver transplantation
      performed between May 2008 and October 2009. All live donor hepatectomies were
      carried out by a single surgeon. RESULTS: A total of 26 live donor procedures for
      paediatric liver transplantation were performed, of which 11 were LLS and 11 OLS;
      four left hepatectomies were excluded. The LLS group had a significantly shorter
      hospital stay (mean(s.d.) 6.9(0.3) versus 9.8(0.9) days; P = 0.001) and time to
      oral diet (2.1(0.3) versus 2.7(0.4) days; P = 0.012). Duration of operation,
      blood loss, warm ischaemia time and out-of-pocket medical costs were comparable
      between groups. There was no death in either donor group and only one
      complication, a wound seroma, in the OLS group. CONCLUSION: LLS seemed to be a
      safe, feasible and reproducible procedure, and was associated with reduced
      hospital stay.

PMID- 21717425
TI  - Zinc finger E-box binding factor 1 plays a central role in regulating Epstein
      Barr virus (EBV) latent-lytic switch and acts as a therapeutic target in EBV
      associated gastric cancer.
AB  - BACKGROUND: The role of Epstein-Barr virus (EBV) infection in gastric
      carcinogenesis remains largely unknown. The authors studied the effects of zinc
      finger E-box binding factor 1 (ZEB1) on latent-lytic switch of EBV infection in
      gastric cancer and explored the importance of EBV in gastric carcinogenesis.
      METHODS: Loss or gain of ZEB1 function was obtained by ZEB1 small-interfering RNA
      (siRNA) knock-down or forced ZEB1 re-expression. Cell growth was evaluated by
      cell viability and colony formation assays, and the cell cycle was assessed by
      flow cytometry. EBV was detected using quantitative polymerase chain reaction
      (PCR) and in situ hybridization analyses. RESULTS: ZEB1 knock-down in a latent
      EBV-infected gastric cancer cell line (YCC10) increased lytic gene BamHI W
      leftward reading frame 1 (BZLF1) expression and decreased the expression of
      latent gene EB nuclear antigen 1 (EBNA1) concomitant with the inhibition of cell
      viability (P < .05) and S-phase DNA synthesis (P < .01). ZEB1 depletion combined
      with ganciclovir revealed a further reduction in cell viability (P < .001). ZEB1
      knock-down induced cell apoptosis and the up-regulation of caspase 3 and
      poly(adenosine diphosphate-ribose) polymerase cleavage. Conversely, ectopic
      overexpression of ZEB1 in a lytic EBV-infected gastric cancer cell line (AGS-EBV)
      inhibited BZLF1 promoter (Zp) activity, BZLF1 expression, and apoptosis and
      promoted cell growth. EBV infection was detected in 11.3% (80 of 711) of gastric
      cancers. The presence of EBV was associated with age, men, and intestinal type
      cancer. CONCLUSIONS: ZEB1 was confirmed as a key mediator of the latent-lytic
      switch of EBV-associated gastric cancer, a distinct subtype with different
      clinicopathologic features. The current results indicated that inhibition of ZEB1
      may be a potential target for EBV-associated gastric cancer therapy.

PMID- 21717426
TI  - Characterization of the gene structure, functional significance, and clinical
      application of RNF180, a novel gene in gastric cancer.
AB  - BACKGROUND: By using genome-wide methylation screening, the authors identified
      ring finger protein 180 (RNF180) as preferentially methylated in cancer. This
      study was undertaken to clarify its structure and functional role in gastric
      cancer. METHODS: The transcription start site and core functional promoter region
      of RNF180 were revealed by 5' rapid amplification of cDNA ends and luciferase
      activity assays. Promoter methylation was detected by combined bisulfite
      restriction analysis and bisulfite genomic sequencing. Cell growth was detected
      by colony formation assay, apoptosis by annexin V assay, and RNF180 target genes
      by cDNA microarray. RESULTS: The authors revealed the transcription start site of
      RNF180 gene and identified the functional core promoter region (-202/+372) in the
      CpG island, which could be silenced by in vitro methylation assay. RNF180 was
      silenced in 6 of 7 gastric cancer cell lines and significantly down-regulated in
      primary gastric cancers compared with adjacent normal tissues (P = .001). Loss of
      gene expression was associated with promoter methylation. Re-expression of RNF180
      suppressed cell growth (P < .001) and induced apoptosis (P < .05), which were
      mediated by up-regulating the antiproliferation regulators MTSS1 and CDKN2A and
      the proapoptotic mediator TIMP3. Promoter methylation of RNF180 was detected in
      76% (150 of 198) of primary gastric cancers and 55% (11 of 20) of intestinal
      metaplasia, but in none of 23 normal gastric tissues. Methylated RNF180 DNA was
      detected in the plasma of 56% of gastric cancer patients, but not in healthy
      controls (P = .003). Patients with low or loss of RNF180 expression had
      significantly poorer overall survival. CONCLUSIONS: RNF180 is a novel potential
      tumor suppressor in gastric carcinogenesis and has potential clinical utility as
      a biomarker for gastric cancer patients.

PMID- 21717427
TI  - The impact of kidney function on the outcome of metastatic renal cell carcinoma
      patients treated with vascular endothelial growth factor-targeted therapy.
AB  - BACKGROUND: A study was undertaken to investigate the effect of baseline renal
      function on treatment outcome in patients treated with vascular endothelial
      growth factor (VEGF)-targeted therapy for metastatic renal cell carcinoma (mRCC).
      METHODS: Retrospective data from 6 North American cancer centers (3 US and 3
      Canadian) were pooled to identify patients with mRCC treated with VEGF-targeted
      therapy. Patient characteristics, response rate, time to treatment failure, and
      overall survival were collected. The Modification of Diet in Renal Disease
      formula was used at therapy initiation for calculation of glomerular filtration
      rate (GFR). RESULTS: Five hundred twenty-nine patients with mRCC who received
      sunitinib (n = 323), sorafenib (n = 165), or bevacizumab (n = 41) were included
      in this analysis. Patient characteristics included: 74% male, median age 61
      years, and median GFR 60.1 mL/min/1.73 m(2) (range, 6.5-174.2). On univariate
      analysis, patients with a GFR <60 (n = 262) were more likely to have had a
      previous nephrectomy (P < .0001) and to be older (P < .0001), but were less
      likely to have poor prognostic features such as anemia (P = .041), hypercalcemia
      (P = .008), neutrophilia (P = .039), thrombocytosis (P < .0001), short diagnosis
      to treatment interval (P = .007), and low Karnofsky performance status (P =
      .051). GFR <60, when adjusted for poor risk factors, did not have an impact on
      type of objective response (odds ratio, 1.31; 95% confidence interval [CI], 0.74
      2.32; P = .359), time to treatment failure (hazard ratio [HR], 0.97; 95% CI, 0.79
      1.19; P = .772), or overall survival (HR, 0.90; 95% CI, 0.69-1.17; P = .439).
      CONCLUSIONS: Renal function at therapy initiation does not adversely affect the
      efficacy of VEGF-targeted therapy in mRCC. Clinicians should not avoid treating
      patients with impaired baseline renal function.

PMID- 21717428
TI  - Disseminated tumor cells predict survival after neoadjuvant therapy in primary
      breast cancer.
AB  - BACKGROUND: Tumor cells that disseminate to the bone marrow (disseminated tumor
      cells [DTCs]) have been identified in 30% of patients with stage I through II
      breast cancer (BC) and predict outcome. Neoadjuvant chemotherapy (NACT) is
      effective in reducing the size of primary tumors or eradicating lymph node
      metastases before surgery, but little is known regarding the presence or
      significance of DTCs after NACT. METHODS: The authors evaluated DTCs in 95
      patients with clinical stage I through III BC. Bone marrow samples were collected
      after completion of NACT at the time they underwent surgery for primary BC. DTCs
      were assessed using an anticytokeratin antibody cocktail. Primary tumor markers,
      the extent of lymph node (LN) involvement, they type of NACT administered, and
      response to NACT were compared with presence of DTCs. Chi-square and Fisher exact
      tests were used for statistical analyses. RESULTS: The median patient age at
      diagnosis was 51 years, and the median follow-up was 24 months. Forty-six percent
      of patients had tumors classified as T1/T2, 20% had T3 tumors, 34.5% had T4
      tumors, and 81% had lymph node metastasis before NACT. DTCs were identified in
      26% of patients after NACT. No associations were observed between DTCs and
      primary tumor characteristics or LN involvement. A pathologic complete response
      was observed in 25 patients (26%) but was not predictive of DTCs after NACT (P =
      .83). DTCs after NACT predicted worse BC-specific survival (P < .02).
      CONCLUSIONS: The presence of DTCs was an independent predictor of outcome after
      NACT. The current results indicated that monitoring hematogenous micrometastatic
      disease after NACT may be useful in selecting patients who might benefit from
      additional systemic adjuvant therapies.

PMID- 21717429
TI  - Genetic variants of the nonhomologous end joining gene LIG4 and severe radiation
      pneumonitis in nonsmall cell lung cancer patients treated with definitive
      radiotherapy.
AB  - BACKGROUND: Nonhomologous end joining (NHEJ) is a pathway that repairs DNA double
      strand breaks (DSBs) to maintain genomic stability in response to irradiation.
      The authors hypothesized that single nucleotide polymorphisms (SNPs) in NHEJ
      repair genes may affect clinical outcomes in patients with nonsmall cell lung
      cancer (NSCLC) who receive definitive radio(chemo)therapy. METHODS: The authors
      genotyped 5 potentially functional SNPs-x-ray repair complementing defective
      repair in Chinese hamster cells 4 (XRCC4) reference SNP (rs) number rs6869366 (
      1394 guanine to thymine [-1394G->T] change) and rs28360071 (intron 3,
      deletion/insertion), XRCC5 rs3835 (guanine to adenine [G->A] change at nucleotide
      2408), XRCC6 rs2267437 (-1310 cytosine to guanine [C->G) change], and DNA ligase
      IV (LIG4) rs1805388 (threonine-to-isoleucine change at codon 9 [T9I])-and
      estimated their associations with severe radiation pneumonitis (RP) (grade >=3)
      in 195 patients with NSCLC. RESULTS: A predictive role in radiation pneumonitis
      (RP) development was observed for the LIG4 SNP rs1805388 (adjusted hazard ratio,
      2.08; 95% confidence interval, 1.04-4.12; P = .037 for the CT/TT genotype vs the
      CC genotype). In addition, men with the TT genotype of the XRCC4 rs6869366 SNP
      and women with AG + AA genotypes of the XRCC5 rs3835 SNP also were at increased
      risk of developing severe RP. CONCLUSIONS: The current results indicated that
      NHEJ genetic polymorphisms, particularly LIG4 rs1805388, may modulate the risk of
      RP in patients with NSCLC who receive definitive radio(chemo)therapy. Large
      studies will be needed to confirm these findings.

PMID- 21717430
TI  - Genetic variants of the p53 and p73 genes jointly increase risk of second primary
      malignancies in patients after index squamous cell carcinoma of the head and
      neck.
AB  - BACKGROUND: Because of the structural and biochemical similarities between the
      antitumor p53 and p73 proteins, the authors hypothesized that individuals who
      carry high-risk genotypes of p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms
      have a higher risk of developing second primary malignancy (SPM) after index
      squamous cell carcinoma of the head and neck (SCCHN). METHODS: A cohort of 1269
      patients with index cases of SCCHN was recruited between May 1995 and January
      2007 at The University of Texas MD Anderson Cancer Center and followed for SPM
      development. Patients were genotyped for p53 codon 72 and p73 G4C14-to-A4T14
      polymorphisms. A log-rank test and Cox proportional hazard models were used to
      compare SPM-free survival and SPM risk among different risk groups with the
      combined risk genotypes of the 2 polymorphisms. RESULTS: The data demonstrated
      that patients with p53 WP + PP and p73 GC/GC genotypes had a worse SPM-free
      survival and an increased SPM risk compared with the corresponding p53 WW and p73
      GC/AT + AT/AT genotypes. After combining the 2 polymorphisms, a borderline
      significantly or significantly reduced SPM-free survival and increased SPM risk
      were observed in the medium-risk group (p53 WW and p73 GC/GC or p53 P carriers
      and p73 AT carriers) and high-risk group (p53 P carriers and p73 GC/GC) compared
      with low-risk group (p53 WW and p73 AT carriers), respectively. CONCLUSIONS: The
      results suggest an increased risk of SPM after index SCCHN with both p53 and p73
      polymorphisms individually and in combination.

PMID- 21717431
TI  - Early stage squamous cell cancer of the oral tongue--clinicopathologic features
      affecting outcome.
AB  - BACKGROUND: The objective of this study was to report the authors' experience in
      the management of patients with early stage squamous cell cancer (SCC) of the
      oral tongue and determine clinicopathologic factors predictive of outcome.
      METHODS: Two hundred sixteen patients with early stage (cT1T2N0) SCC of the oral
      tongue were identified from a pre-existing database of patients with oral cancer
      who were treated at Memorial Sloan-Kettering Cancer Center from 1985 to 2005.
      Patient, tumor, and treatment characteristics were recorded. Overall survival
      (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were
      calculated using the Kaplan-Meier method. Predictors of outcome were identified
      using multivariate analysis. RESULTS: With a median follow-up of 80 months
      (range, 1-186 months), the 5-year DSS, OS, and RFS rates were 86%, 79%,and 70%,
      respectively. Local, neck, and distant recurrences occurred in 24 patients (11%),
      40 patients (18%), and 5 patients (2%), respectively. Multivariate analysis
      identified occult neck metastases as the main independent predictor of OS, DSS,
      and RFS; patients who had occult metastases had a 5-fold increased risk of dying
      of disease compared with patients who did not have occult metastases (5-year DSS,
      85.5% vs 48.5%; P = .001). A positive surgical margin was the main independent
      predictor for local RFS (91% vs 66% for a negative surgical margin; P = .0004),
      and depth of invasion was the main predictor for neck RFS (91% vs 73% for depth
      of invasion <2 mm and >2 mm, respectively; P = .02). CONCLUSIONS: In the authors'
      experience, patients with early stage oral tongue cancer have excellent outcomes.
      In the current study, the presence of occult metastases was the main predictor of
      survival outcome.

PMID- 21717432
TI  - Conflict of interest in oncology publications: a survey of disclosure policies
      and statements.
AB  - BACKGROUND: Disclosure of conflicts of interest in biomedical research is
      receiving increased attention. The authors sought to define current disclosure
      policies and how they relate to disclosure statements provided by authors in
      major oncology journals. METHODS: The authors identified all oncology journals
      listed in the Thomson Institute for Scientific Information and sought their
      policies on conflict-of-interest disclosure. For a subset of journals with an
      Impact Factor >2.0, they catalogued the number and type of articles and the
      details of the published disclosures in all papers from the 2 most recent issues.
      RESULTS: Disclosure policies were provided by 112 of 131 journals (85%); 99 (88%)
      of these requested that authors disclose conflicts of interest (mean Impact
      Factor for these journals: 4.6), whereas the remaining 13 (12%) did not (mean
      Impact Factor: 2.9). Ninety-three journals (94%) required financial disclosure,
      and 42 (42%) also sought nonfinancial disclosures. For a subset of 52 higher
      impact journals (Impact Factor >2.0), we reviewed 1734 articles and identified
      published disclosures in 51 journals (98%). Many of these journals (31 of 51,
      61%) included some disclosure statement in >90% of their articles. Among 27
      journals that published editorials/commentaries, only 14 (52%) included
      disclosures with such articles. There was no publication of any nonfinancial
      conflicts of interest in any article reviewed. CONCLUSIONS: Disclosure policies
      and the very definition of conflict of interest varied considerably among
      journals. Although most journals had some policy in this area, a substantial
      proportion did not publish disclosure statements consistently, with deficiencies
      particularly among editorials and commentaries.

PMID- 21717433
TI  - Proteomic biomarkers in combination with CA 125 for detection of epithelial
      ovarian cancer using prediagnostic serum samples from the Prostate, Lung,
      Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
AB  - BACKGROUND: When epithelial ovarian cancer is detected at an early stage (I-II),
      the 5-year survival rate is between 70% and 90%; whereas, when it is detected in
      late stages (III-IV), the 5-year survival rate slips to <30%. In a previous
      report, the authors observed that proteomic biomarkers and cancer antigen 125 (CA
      125) exhibited a sensitivity of 84% at a specificity of 98% for identifying sera
      from patients who had stage I disease at the time of surgery, significantly
      improving the sensitivity of CA 125 alone. The challenge, however, is to detect
      ovarian cancer before clinical diagnosis. The current study was part of a large
      effort to compare different multimarker biomarker panels for the early detection
      of ovarian cancer. Several biomarkers were evaluated alone and in combination
      with CA 125 in prediagnostically collected sera from women in the Prostate, Lung,
      Colorectal, and Ovarian Cancer Screening Trial. METHODS: Proximal prediagnostic
      sera from 118 women with ovarian cancer (cases) and from 951 age-matched women
      (controls) (8 controls per case, including 4 randomly selected from the general
      population, 2 with CA 125 levels >= 35 U/mL, and 2 with a positive family history
      of breast/ovarian cancer) were analyzed using the CA 125 immunoassay and surface
      enhanced laser desorption and ionization time-of-flight mass spectrometry to
      measure 7 proteins (apolipoprotein A1, truncated transthyretin, transferrin,
      hepcidin, beta-2 microglobulin, connective tissue activating protein III), and
      interalpha-trypsin inhibitor heavy-chain 4). Data were analyzed by 2 statistical
      strategies that combined the 7 markers and CA 125 into 1 predictive score for
      disease classification. RESULTS: CA 125 levels were elevated (>= 35 U/mL) in
      61.5% of 65 patients who had CA 125 data available from samples that were
      collected <12 months before cancer diagnosis; however, levels of the additional 7
      biomarkers were not different between cases and the 3 control groups individually
      or combined. Two panels that combined CA 125 and the 7 biomarkers failed to
      improve the sensitivity of CA 125 alone. CONCLUSIONS: In contrast to earlier
      findings from analyzes of postdiagnostically collected sera, the addition of 7
      biomarkers to CA 125 did not improve sensitivity for preclinical diagnosis beyond
      CA 125 alone.

PMID- 21717434
TI  - The association of robotic surgical technology and hospital prostatectomy
      volumes: increasing market share through the adoption of technology.
AB  - BACKGROUND: Despite limited and conflicting evidence for the efficacy of newly
      developed robotic technology for laparoscopic prostatectomy, this technology is
      spreading rapidly. Because the newer technology is more costly, reasons for this
      rapid adoption are unclear. The authors of this report sought to determine
      whether hospital acquisition of robotic technology was associated with volume of
      prostate cancer surgery. METHODS: The inpatient dataset of claims records from
      2002 to 2008 and the acquisition dates of robotic technology were used to examine
      the rates of prostatectomy in Wisconsin hospitals. In analyses that accounted for
      hospital and referral region characteristics, changes in hospital prostatectomy
      volume were examined for their association with technology acquisition. Overall
      trends in the rate of prostatectomy also were examined over the study period.
      RESULTS: In total, 10,021 prostatectomies were performed in 52 hospitals in
      Wisconsin's 8 health referral regions during the study period. The mean quarterly
      prostatectomy volume in hospitals that did not acquire the technology was 4.5 in
      2002 and 3.1 in 2007/2008. In contrast, the mean quarterly prostatectomy volume
      in hospitals that went on to acquire robotic technology was 16.5 in 2002 and 24.8
      in 2007/2008. In adjusted models, the acquisition of a robot was associated with
      a 114% annual increase (95% confidence interval, 62%-177% annual increase) in
      hospital prostatectomy volume. The average Wisconsin hospital prostatectomy
      volume was unchanged during 2002 through 2006 but increased by 25.6% in 2007.
      CONCLUSIONS: Robotic technology acquisition occurred rapidly in Wisconsin
      hospitals, and hospitals that acquired a robot had large increases in
      prostatectomy volume.

PMID- 21717435
TI  - A scoring system to predict the risk of death during induction with anthracycline
      plus cytarabine-based chemotherapy in patients with de novo acute myeloid
      leukemia.
AB  - BACKGROUND: A prognostic index to predict induction death in adult patients
      receiving induction chemotherapy for de novo acute myeloid leukemia (AML) was
      developed. METHODS: The authors analyzed 570 patients (aged 16-70 years) included
      in 2 multicenter trials of the CETLAM Group to develop a scoring system (study
      cohort). The scoring system was tested in 209 patients from an external single
      institution (validation cohort). Induction regimens consisted of anthracycline
      and cytarabine combination with or without etoposide. Induction death was defined
      as death in the first 42 days without evidence of leukemic resistance. RESULTS:
      The cumulative incidence of induction death was 11% in the study cohort and 18%
      in the validation cohort. Median age was 48 years in the study cohort and 56
      years in the validation cohort (P < .001). Multivariate analysis in the study
      cohort showed the following adverse risk factors for induction death: leukocyte
      count >100 * 10(9) /L, serum creatinine >1.2 mg/dL, and age >=50 years. According
      to these factors, the authors developed a predictive score: low risk (no risk
      factors), intermediate risk (1 factor), and high risk (2 or 3 factors). The
      cumulative incidence of induction death in the 3 respective groups was 5%, 13%,
      and 26% (P < .001). The scoring system was applied in the validation cohort,
      resulting in cumulative incidence rates of induction death of 6%, 19%, and 32%,
      for the low-risk, intermediate-risk, and high-risk categories, respectively (P <
      .001). CONCLUSIONS: By using this validated and simple scoring system, the risk
      of induction death in patients with AML can be predicted accurately. The score
      may be helpful to design risk-adapted induction strategies.

PMID- 21717437
TI  - The rapid uptake of robotic prostatectomy and its collateral effects.

PMID- 21717436
TI  - Trends in radical prostatectomy: centralization, robotics, and access to urologic
      cancer care.
AB  - BACKGROUND: Robotic surgery has been widely adopted for radical prostatectomy. We
      hypothesized that this change is rapidly shifting procedures away from hospitals
      that do not offer robotics and consequently increasing patient travel. METHODS: A
      population-based observational study of all prostatectomies for cancer in New
      York, New Jersey, and Pennsylvania from 2000 to 2009 was performed using hospital
      discharge data. Hospital procedure volume was defined as the number of
      prostatectomies performed for cancer in a given year. Straight-line travel
      distance to the treating hospital was calculated for each case. Hospitals were
      contacted to determine the year of acquisition of the first robot. RESULTS: From
      2000 to 2009, the total number of prostatectomies performed annually increased
      substantially. The increase occurred almost entirely at the very high-volume
      centers (>= 106 prostatectomies/year). The number of hospitals performing
      prostatectomy fell 37% from 2000 to 2009. By 2009, the 9% (21/244) of hospitals
      that had very high volume performed 57% of all prostatectomies, and the 35%
      (86/244) of hospitals with a robot performed 85% of all prostatectomies. The
      median travel distance increased 54% from 2000 to 2009 (P<.001). The proportion
      of patients traveling >= 15 miles increased from 24% to 40% (P < .001).
      CONCLUSIONS: Over the past decade, the number of radical prostatectomies
      performed has risen substantially. These procedures have been increasingly
      centralized at high-volume centers, leading to longer patient travel distances.
      Few prostatectomies are now performed at hospitals that do not offer robotic
      surgery.

PMID- 21717438
TI  - A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for
      clinical T2-T4aN0-N2M0 bladder cancer.
AB  - BACKGROUND: Despite evidence supporting perioperative chemotherapy, few
      randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder
      cancer. Consequently, the standard of care regarding the timing of chemotherapy
      for locally advanced bladder cancer remains controversial. We compared patient
      outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2-T4aN0
      N2M0 bladder cancer. METHODS: In a retrospective review of a single institutional
      database from 1988 through 2009, we identified patients receiving neoadjuvant or
      adjuvant multiagent platinum-based systemic chemotherapy for locally advanced
      bladder cancer. Survival analysis was performed comparing disease-specific
      survival (DSS) and overall survival (OS). RESULTS: A total of 146 patients
      received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of
      these, 84% (122/146) received cisplatin-based chemotherapy compared with
      carboplatin-based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin
      based chemotherapy were treated with
      methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the
      remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In
      multivariable analysis, there was no significant difference in DSS (P = .46) or
      OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was
      statistically significant improvement in DSS when patients received neoadjuvant
      GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence
      interval, 1.01-112.2). CONCLUSION: In this study, there was no statistically
      significant difference in OS and DSS between patients receiving neoadjuvant
      versus adjuvant systemic platinum-based chemotherapy for locally advanced bladder
      cancer. In addition, there was no significant difference between neoadjuvant and
      adjuvant cisplatin- or carboplatin-based chemotherapy. Chemotherapy sequence
      relative to surgery appeared less important than whether or not a patient
      actually received perioperative chemotherapy.

PMID- 21717439
TI  - Better prognosis for patients with del(7q) than for patients with monosomy 7 in
      myelodysplastic syndrome.
AB  - BACKGROUND: Abnormalities involving chromosome 7 are frequent in myelodysplastic
      syndrome (MDS) and suggest a poor prognosis. METHODS: The authors examined the
      hypothesis that the clinical features and survival associated with isolated
      deletion (del) of part of the long arm of chromosome 7 (7q) in MDS are different
      from those associated with isolated monosomy 7 (complete loss of chromosome 7).
      In total, 133 patients with a diagnosis of de novo MDS (according to the World
      Health Organization [WHO] classification) and chromosome 7 abnormalities in the
      Spanish MDS Registry were evaluated retrospectively. Four karyotypic groups were
      identified: isolated del(7q) (n = 29), isolated monosomy 7 (n = 27), del(7q) with
      additional abnormalities (n = 24), and monosomy 7 with additional abnormalities
      (n = 53). RESULTS: Isolated del(7q) was more frequent in patients with less
      advanced MDS according to the WHO classification or the International Prognostic
      Scoring System. In addition, isolated del(7q) was associated with fewer blasts in
      bone marrow than other cytogenetics groups. Survival was significantly superior
      in patients with isolated del(7) than in those with isolated monosomy 7, del(7q)
      with additional abnormalities, or monosomy 7 with additional abnormalities. On
      multivariate analysis, age, the percentage of blasts in bone marrow, and other
      chromosome 7 abnormalities apart from isolated del(7q) were identified as
      independent risk factors for survival. CONCLUSIONS: The current results
      demonstrated that patients who had MDS with isolated del(7q) had some distinct
      clinical-pathologic characteristics as well as better survival than patients who
      had MDS with isolated monosomy 7.

PMID- 21717440
TI  - Measuring response to BCR-ABL inhibitors in chronic myeloid leukemia.
AB  - In patients with chronic myeloid leukemia (CML), the hallmark Philadelphia
      chromosome is the marker of disease that can be detected by conventional
      metaphase cytogenetics, fluorescence in situ hybridization, or polymerase chain
      reaction. The current "gold standard" of treatment response is cytogenetic
      response. Cytogenetic response to imatinib is strongly associated with disease
      progression and survival. Various strategies aimed at improving cytogenetic
      response have been explored, such as escalation of imatinib and switching to the
      newer breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene (BCR
      ABL) inhibitors dasatinib and nilotinib. Data from recent randomized trials of
      dasatinib and nilotinib as first-line therapy of newly diagnosed chronic-phase
      CML suggest that these agents are more effective than imatinib in achieving 6
      month and 12-month complete cytogenetic responses. However, it is still too early
      to know whether or not this early response will translate into a long-term
      survival advantage. In addition, more sensitive assays to detect residual disease
      also may be associated with improved long-term outcomes. The deepest measure of
      response-a complete molecular response-may help identify patients who can stop
      taking imatinib for the short term, although the long-term consequences of this
      strategy remain unknown.

PMID- 21717441
TI  - Medullary thyroid microcarcinoma: a population-level analysis of 310 patients.
AB  - BACKGROUND: Medullary thyroid microcarcinomas (microMTCs) are medullary thyroid
      carcinomas (MTCs) that measure <=1 cm in size for which there is a paucity of
      data on incidence, characteristics, and clinical significance. METHODS: Patients
      who had a diagnosis of microMTC were abstracted from the Surveillance,
      Epidemiology, and End Results database (1988-2007). The data were analyzed using
      chi-square tests, t tests, and log-rank tests; multivariate logistic regression
      was used to identify factors that were associated independently with lymph node
      metastases. Tests for diagnostic accuracy, including likelihood ratio tests and
      post-test probability tests, were computed to evaluate the size-specific
      likelihood of developing lymph node metastases among patients with microMTC.
      RESULTS: In total, 310 patients had microMTC; its incidence increased during the
      study period (P(trend) = .033), and microMTC as a proportion of all MTCs
      increased by 39%. The mean tumor size was 5.7 mm. Thirty-one percent of tumors
      were multifocal, and 7.8% had extrathyroid extension. Lymph node metastases
      occurred in nearly 37% of patients who had any lymph nodes removed (65 of 176
      patients). Nearly 20% of patients had regional disease, and 5% had distant
      metastases. The overall 10-year survival rates for patients with localized,
      regional, and distant disease stages were 96%, 87%, and 50%, respectively (P <
      .001). After adjustment, extrathyroid extension (odds ratio [OR], 41.9; P < .001)
      and tumor size (OR, 1.2; P = .008) retained an independent association with lymph
      node metastases. MTCs that measured <=5 mm were associated with a probability of
      lymph node metastases of approximately 23%, and the probability increased for
      patients who had tumors >5 mm. CONCLUSIONS: The current results indicated that
      microMTCs have significant rates of poor prognostic features known to impact the
      survival of patients with MTC. These microcarcinomas are an important clinical
      entity that requires comprehensive evaluation and surgical management.

PMID- 21717442
TI  - Novel, chimeric, cancer-specific, and radiation-inducible gene promoters for
      suicide gene therapy of cancer.
AB  - BACKGROUND: Although the promoter of the human telomerase reverse transcriptase
      (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it
      has some limitations for clinical use because of its low activity and potential
      toxicity to certain normal cells. To overcome these defects, the authors
      generated novel chimeric hTERT promoters that contained the radiation-inducible
      sequence CC(A/T)(6) GG (known as CArG elements). METHODS: Chimeric hTERT
      promoters were synthesized that contained different numbers of CArG elements, and
      the activity of chimeric promoters was assessed in different cancer cell lines
      and normal cells. The potential of selected promoters to successfully control
      horseradish peroxidase (HRP) and prodrug indole-3-acetic acid (IAA) suicide gene
      therapy was tested in vitro and in vivo. RESULTS: The promoter activity assays
      indicated that the synthetic promoter that contained 6 repeating CArG units had
      the best radiation inducibility than any other promoters that contained different
      numbers of CArG units, and the chimeric promoters retained their cancer-specific
      characteristics. The chimeric promoter was better at driving radiation-inducible
      gene therapy than the control promoters. The sensitizer enhancement ratio of the
      chimeric promoter system determined by clonogenic assay was higher, and the
      chimeric promoter system resulted in a significantly higher apoptotic level
      compared with other promoter systems. The combination of chimeric/promoter
      mediated gene therapy and radiotherapy significantly inhibited tumor volume in a
      xenograft mouse model and resulted in a significant prolongation of survival in
      mice. CONCLUSIONS: The current results indicated that a combinational cancer
      specific promoter system that is responsive to irradiation has great potential
      for improving the efficacy of cancer treatment.

PMID- 21717443
TI  - High-dose cytarabine induction is well tolerated and active in patients with de
      novo acute myeloid leukemia older than 60 years.
AB  - BACKGROUND: High-dose cytarabine (HiDAC) is safe and very effective in younger
      patients with acute myeloid leukemia (AML), but it generally is not well
      tolerated in the elderly. METHODS: The authors explored the safety and
      tolerability of a modified HiDAC induction regimen consisting of 6 daily doses of
      cytarabine at 2 g/m(2) in combination with 3 daily doses of daunorubicin at 45
      mg/m(2) in 59 consecutive patients aged >60 years who had de novo AML diagnosed
      between July 1996 and February 2005. RESULTS: The median patient age was 68 years
      (range, 60-86 years). The regimen was well tolerated. Infections were common and
      occurred in 39% of patients, but cerebellar toxicities occurred in only 7% of
      patients and were reversible. The day-30 induction-related mortality rate was
      10%. Overall, 69% of patients achieved complete remissions (CR), and 80% received
      up to 3 consolidations with HiDAC. The median follow-up for surviving patients
      was 53 months (range, 17-114 months). The median overall survival was 15.3 months
      (range, 1-114 months), and the relapse-free survival was 13.8 months (range, 1
      113 months). Survival for patients who achieved CR was 27 months (range, 2-114
      months). CONCLUSIONS: The modified HiDAC regimen was well tolerated in patients
      aged >60 years with AML and was associated with low induction mortality and high
      rates of CR. Nevertheless, these high remissions still were associated with poor
      overall outcomes.

PMID- 21717444
TI  - Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus
      idarubicin with or without cytarabine in refractory and relapsed acute myeloid
      leukemia.
AB  - BACKGROUND: The p53 antisense oligonucleotide cenersen has been shown to
      sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents.
      METHODS: To determine whether cenersen merits testing in larger efficacy studies,
      an exploratory study of cenersen in combination with idarubicin either alone or
      with 1 of 2 doses of cytarabine was performed in first-salvage AML patients.
      Patients who either had failed to respond to a single induction course or had
      responded to induction but relapsed within 12 months were enrolled. Stopping
      rules based on an expected 14% complete response (CR) rate were applied to each
      treatment arm. RESULTS: Fifty-three patients were treated, and none of the arms
      was terminated for lack of activity. Nearly all patients received a single course
      unless they responded. Ten of the 53 (19%) patients responded (8 CR and 2 CR with
      incomplete platelet recovery). There was a positive trend for a better response
      rate with increasing intensity of chemotherapy in the patients refractory to
      front-line treatment compared with those who had relapsed previously. One-third
      (17/53) of the patients received cenersen inhibitors (acetaminophen and/or high
      dose antioxidants) during treatment, and none of these responded to treatment. No
      unique toxicity was attributed to cenersen. CONCLUSION: The results of this study
      suggested that the combination of cenersen with chemotherapy may have clinical
      efficacy, and additional studies are warranted to explore its full potential.

PMID- 21717445
TI  - Long-term outcomes of BRCA1/BRCA2 testing: risk reduction and surveillance.
AB  - BACKGROUND: For BRCA1/BRCA2 gene testing to benefit public health, mutation
      carriers must initiate appropriate risk management strategies. There has been
      little research examining the long-term use and prospective predictors of the
      full range of risk management behaviors among women who have undergone BRCA1/2
      testing. We evaluated long-term uptake and predictors of risk-reducing mastectomy
      (RRM), risk-reducing bilateral salpingo-oophorectomy (RRBSO), chemoprevention,
      and cancer screening among women at a mean of 5.3 years after testing. METHODS:
      The study participants comprised 465 women who underwent BRCA1/2 testing. Prior
      to genetic counseling, we measured family/personal cancer history,
      sociodemographics, perceived risk, cancer-specific distress, and general
      distress. We contacted patients at a mean of 5.3 years after testing to measure
      use of RRM, RRBSO, chemoprevention, and breast and ovarian cancer screening.
      RESULTS: Among participants with intact breasts and/or ovaries at the time of
      testing, BRCA1/2 carriers were significantly more likely to obtain RRM (37%) and
      RRBSO (65%) compared with women who received uninformative (RRM, 6.8%; RRBSO,
      13.3%) or negative (RRM, 0%; RRBSO, 1.9%) results. Among carriers, precounseling
      anxiety was associated with subsequent uptake of RRM. RRO was predicted by age.
      Carriers were also more likely have used breast cancer chemoprevention and have
      undergone magnetic resonance imaging screening. CONCLUSION: This prospective
      evaluation of the uptake and predictors of long-term management outcomes provides
      a clearer picture of decision making in this population. At a mean of 5.3 years
      after testing, more than 80% of carriers had obtained RRM, RRBSO, or both,
      suggesting that BRCA1/2 testing is likely to have a favorable effect on breast
      and ovarian cancer outcomes.

PMID- 21717446
TI  - Underascertainment of radiotherapy receipt in Surveillance, Epidemiology, and End
      Results registry data.
AB  - BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) registry data have
      been used to suggest underuse and disparities in receipt of radiotherapy. Prior
      studies have cautioned that SEER may underascertain radiotherapy but lacked
      adequate representation to assess whether underascertainment varies by geography
      or patient sociodemographic characteristics. The authors sought to determine
      rates and correlates of underascertainment of radiotherapy in recent SEER data.
      METHODS: The authors evaluated data from 2290 survey respondents with
      nonmetastatic breast cancer, aged 20 to 79 years, diagnosed from June of 2005 to
      February 2007 in Detroit and Los Angeles and reported to SEER registries (73%
      response rate). Survey responses regarding treatment and sociodemographic factors
      were merged with SEER data. The authors compared radiotherapy receipt as reported
      by patients versus SEER records. The authors then assessed correlates of
      radiotherapy underascertainment in SEER. RESULTS: Of 1292 patients who reported
      receiving radiotherapy, 273 were coded as not receiving radiotherapy in SEER
      (underascertained). Underascertainment was more common in Los Angeles than in
      Detroit (32.0% vs 11.25%, P < .001). On multivariate analysis, radiotherapy
      underascertainment was significantly associated in each registry (Los Angeles,
      Detroit) with stage (P = .008, P = .026), income (P < .001, P = .050), mastectomy
      receipt (P < .001, P < .001), chemotherapy receipt (P < .001, P = .045), and
      diagnosis at a hospital that was not accredited by the American College of
      Surgeons (P < .001, P < .001). In Los Angeles, additional significant variables
      included younger age (P < .001), nonprivate insurance (P < .001), and delayed
      receipt of radiotherapy (P < .001). CONCLUSIONS: SEER registry data as currently
      collected may not be an appropriate source for documentation of rates of
      radiotherapy receipt or investigation of geographic variation in the radiation
      treatment of breast cancer.

PMID- 21717447
TI  - The enigma of myxofibrosarcoma of the extremity.
AB  - BACKGROUND: The reported high rate of local recurrence (LR) in myxofibrosarcoma
      raises the question of whether this sarcoma histology should be considered
      radioresistant. In this study, the authors compared rates and patterns of LR of
      high-grade (HG) myxofibrosarcoma with rates and patterns of HG leiomyosarcoma,
      which was chosen because of the similarity in incidence and general treatment
      approach. METHODS: Two hundred two patients with primary, nonmetastatic extremity
      myxofibrosarcoma (n = 114) and leiomyosarcoma (n = 88) underwent limb-sparing
      surgery and were followed prospectively. All 202 patients had HG tumors, and 138
      patients (68%) received adjuvant radiation therapy. RESULTS: The groups were
      comparable in terms of age, sex, and receipt of chemotherapy. Compared with
      leiomyosarcoma, myxofibrosarcoma presented more frequently with tumors >5 cm (P <
      .001), deep location (P = .036), and upper extremity site (P = .015). In
      addition, rates of positive/close margins (P < .001) and the receipt of radiation
      therapy (P < .001) were significantly higher in the myxofibrosarcoma group. The 5
      year overall LR rate was not significantly different according to histology
      (14.6% for myxofibrosarcoma, 13.2% for leiomyosarcoma; P = .594). The only
      predictor of LR for the whole cohort of patients was positive/close margins (P =
      .01). Of 17 myxofibrosarcoma LRs, 8 (47%) occurred out of field, versus 1 of 12
      (8%) leiomyosarcoma LRs (P = .04). Leiomyosarcoma more commonly recurred
      distantly (54.1% vs 24.3% at 5 years; P = .014). CONCLUSIONS: Despite more
      adverse clinical features, myxofibrosarcoma recurred distantly less often than
      leiomyosarcoma, whereas the LR rates were comparable between the 2 groups,
      suggesting that adjuvant radiation therapy is effective in myxofibrosarcoma.
      Myxofibrosarcoma LRs more commonly occurred out of field. Reduction in radiation
      field margins may not be advisable in patients with myxofibrosarcoma.

PMID- 21717448
TI  - IDH1 mutations in grade II astrocytomas are associated with unfavorable
      progression-free survival and prolonged postrecurrence survival.
AB  - BACKGROUND: The favorable prognostic impact of mutations in the IDH1 gene is well
      documented for malignant gliomas; its influence on World Health Organization
      (WHO) grade II astrocytomas, however, is still under debate. METHODS: A
      previously published database of 127 predominantly surgically treated patients
      harboring WHO grade II astrocytomas was revisited. Patients were screened for
      TP53 mutations (sequencing analysis), IDH1 mutations (pyrosequencing), and MGMT
      promoter methylation (methylation-specific polymerase chain reaction and
      bisulfite sequencing). Endpoints were overall survival, progression-free survival
      (PFS), time to malignant transformation, and postrecurrence survival.
      Radiotherapy was usually withheld until tumor progression/malignant
      transformation occurred. RESULTS: IDH1 mutations, TP53 mutations, and methylated
      MGMT promoters were seen in 78.1%, 51.2%, and 80.0% of the analyzed tumors,
      respectively. IDH1 mutations, which were significantly associated with TP53
      mutations and/or MGMT promoter methylation (P < .001), resulted in shortened PFS
      (median, 47 vs 84 months; P = .004); postrecurrence survival, however, was
      significantly increased in those patients undergoing malignant transformation
      (median, 49 vs 13.5 months; P = .006). Overall survival was not affected by IDH1.
      A similar pattern of influence was seen for MGMT promoter methylation. Methylated
      tumors did significantly worse (better) in terms of PFS (postrecurrence
      survival); a low number of unmethylated tumors, however, limited the power of
      this analysis. Conversely, TP53 mutations were stringently associated with a
      worse prognosis throughout the course of the disease. CONCLUSIONS: IDH1 mutations
      are associated with a Janus headlike phenomenon; unfavorable prognostic influence
      on PFS turns into favorable impact on postrecurrence survival. A similar pattern
      of influence might exist for MGMT methylation.

PMID- 21717449
TI  - Exemestane versus anastrozole as front-line endocrine therapy in postmenopausal
      patients with hormone receptor-positive, advanced breast cancer: final results
      from the Spanish Breast Cancer Group 2001-03 phase 2 randomized trial.
AB  - BACKGROUND: Several aromatase inhibitor studies have reported variations in the
      inhibitory potency of these agents that could lead to differences in clinical
      outcomes. In the current study, the authors formally evaluated the activity of
      anastrozole and exemestane in postmenopausal women with hormone-responsive,
      advanced breast cancer. METHODS: Postmenopausal women who had measurable disease
      according to Response Evaluation Criteria in Solid Tumors and had not received
      previous endocrine therapy for advanced breast cancer were randomized to receive
      either oral exemestane 25 mg daily or oral anastrozole 1 mg daily until they had
      disease progression. The primary endpoint was the objective response rate (ORR),
      and secondary endpoints included the clinical benefit rate (CBR), time to
      progression (TTP), overall survival, and safety. Crossover to the other aromatase
      inhibitor was permitted at the time of disease progression; ORR, CBR, and TTP
      after second-line treatment also were explored. RESULTS: In total, 103 patients
      were enrolled. The median patient age was 71.6 years, 52.4% of patients had
      visceral disease, and 75.8% of patients had >= 2 disease sites. Half of the
      patients had received previous tamoxifen, and 60% had received previous
      chemotherapy. The efficacy observed in the exemestane and anastrozole groups was
      an ORR of 36.2% and 46%, respectively; a CBR of 59.6% and 68%, respectively, and
      a TTP of 6.1 months and 12.1 months, respectively. At progression, 28 patients
      crossed over to the other aromatase inhibitor, including 16 patients who switched
      to exemestane (CBR, 43.7%; TTP, 4.4 months) and 12 patients who switched to
      anastrozole (CBR, 8.3%; TTP, 2 months). Both drugs were generally well tolerated,
      and no study drug-related serious adverse events were reported. CONCLUSIONS: In
      this phase 2 randomized trial, no significant differences in clinical activity
      were observed in favor of exemestane to justify a superiority phase 3 trial
      design in the first-line setting.

PMID- 21717450
TI  - The long-term postsurgical prognosis of patients with pineoblastoma.
AB  - BACKGROUND: For this report, the authors comprehensively summarized the existing
      literature on patients with pineoblastoma and identified the variables and
      treatments that had an impact patient on outcomes. METHODS: A comprehensive
      search identified 109 studies that collectively described the outcomes of
      patients with pineoblastoma. Individual patient data were classified based on
      treatment and were subjected to univariate comparisons. Cox regression analysis
      included comparisons of survival outcomes controlling for age, extent of
      resection, and treatment group, and between-group survival comparisons were
      performed using the Kendall tau (rank correlation) statistic. RESULTS: Two
      hundred ninety-nine patients met inclusion criteria. The overall survival rate
      was 54% (175 of 299 patients) at a mean follow-up of 31 +/- 1.9 months (range, 1
      159 months). The analyses demonstrated a markedly worse prognosis for children
      aged <= 5 years compared with older patients (5-year survival rate: 15% for
      children aged <= 5 years vs 57% for children aged >= 5 years; log-rank P <
      .00001). In addition, a graded increase in survival was observed with increasing
      degrees of resection (5-year survival rate: 84% for patients who underwent gross
      total resection vs 53% for patients who underwent subtotal resection vs 29% for
      patients who underwent debulking; log-rank P < .0001). Multivariate analysis
      indicated that not achieving gross total resection markedly worsened patient
      survival (subtotal resection: hazard ratio, 6.47; 95% confidence interval, 2.3
      19; P = .001. debulking: hazard ratio, 9.27; 95% confidence interval, 3.2-27; P <
      .0001). CONCLUSIONS: The current findings emphasize the importance of aggressive
      surgical resection in the treatment of pineoblastoma. In addition, the authors
      conclude that clinical trials should not mix young patients with older patients
      or patients who undergo subtotal resection with patients who undergo gross total
      resection, because such heterogeneity may alter the variability of responses to
      treatment and reduce the likelihood of success.

PMID- 21717451
TI  - Cholecystectomy and risk of laryngeal and pharyngeal cancer.
AB  - Duodeno-gastro-esophageal reflux of bile might cause laryngeal and pharyngeal
      cancer, but more research is required. Since cholecystectomy is followed by an
      increased risk such reflux, the risk of developing laryngeal or pharyngeal cancer
      after cholecystectomy was addressed. A population-based cohort study was
      conducted in Sweden during the period 1965-2008. The number of laryngeal or
      pharyngeal cancer cases observed in a large cohort of cholecystectomized patients
      was compared with the expected number, calculated from the entire Swedish
      population of corresponding age, gender and calendar year. Risk of laryngeal or
      pharyngeal cancer was calculated as standardized incidence ratio (SIR) with 95%
      confidence interval (CI). The cholecystectomy cohort included 345,251 patients
      who were followed up for 1-43 years and contributed 4,854,969 person-years at
      risk. The 192 new cases of laryngeal cancer and the 175 cases of pharyngeal
      cancer were not greater than the expected, providing SIR 0.99 (95% CI 0.85-1.14)
      and SIR 1.06 (95% CI 0.91-1.23), respectively. A longer latency period after
      cholecystectomy was not associated with any increased risk of any of these
      tumors. No differences between age groups or sexes were detected. Analyses
      restricted to verified squamous-cell carcinomas revealed similar results. In
      conclusion, cholecystectomy does not appear to be followed by any increased risk
      of laryngeal or pharyngeal cancer.

PMID- 21717452
TI  - Dietary intake of heme iron and risk of gastric cancer in the European
      prospective investigation into cancer and nutrition study.
AB  - Even though recent studies suggest that a high intake of heme iron is associated
      with several types of cancer, epidemiological studies in relation to gastric
      cancer (GC) are lacking. Our previous results show a positive association between
      red and processed meat and non cardia gastric cancer, especially in Helicobacter
      pylori infected subjects. The aim of the study is to investigate the association
      between heme iron intake and GC risk in the European prospective investigation
      into cancer and nutrition (EURGAST-EPIC). Dietary intake was assessed by
      validated center-specific questionnaires. Heme iron was calculated as a type
      specific percentage of the total iron content in meat intake, derived from the
      literature. Antibodies of H. pylori infection and vitamin C levels were measured
      in a sub-sample of cases and matched controls included in a nested case-control
      study within the cohort. The study included 481,419 individuals and 444 incident
      cases of GC that occurred during an average of 8.7 years of followup. We observed
      a statistically significant association between heme iron intake and GC risk (HR
      1.13 95% CI: 1.01-1.26 for a doubling of intake) adjusted by sex, age, BMI,
      education level, tobacco smoking and energy intake. The positive association
      between heme iron and the risk of GC was statistically significant in subjects
      with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.01-2.35). We found
      a positive association between heme iron intake and gastric cancer risk.

PMID- 21717453
TI  - 3-Deazaneplanocin A is a promising therapeutic agent for the eradication of tumor
      initiating hepatocellular carcinoma cells.
AB  - Recent advances in stem cell biology have identified tumor-initiating cells
      (TICs) in a variety of cancers including hepatocellular carcinoma (HCC). Polycomb
      group gene products such as BMI1 and EZH2 have been characterized as general self
      renewal regulators in a wide range of normal stem cells and TICs. We previously
      reported that Ezh2 tightly regulates the self-renewal and differentiation of
      murine hepatic stem/progenitor cells. However, the role of EZH2 in tumor
      initiating HCC cells remains unclear. In this study, we conducted loss-of
      function assay of EZH2 using short-hairpin RNA and pharmacological inhibition of
      EZH2 by an S-adenosylhomocysteine hydrolase inhibitor, 3-deazaneplanocin A
      (DZNep). Both EZH2-knockdown and DZNep treatment impaired cell growth and
      anchorage-independent sphere formation of HCC cells in culture. Flow cytometric
      analyses revealed that the two approaches decreased the number of epithelial cell
      adhesion molecule (EpCAM)(+)  tumor-initiating cells. Administration of 5
      fluorouracil (5-FU) or DZNep suppressed the tumors by implanted HCC cells in non
      obese diabetic/severe combined immunodeficient mice. Of note, however, DZNep but
      not 5-FU predominantly reduced the number of EpCAM(+)  cells and diminished the
      self-renewal capability of these cells as judged by sphere formation assays. Our
      findings reveal that tumor-initiating HCC cells are highly dependent on EZH2 for
      their tumorigenic activity. Although further analyses of TICs from primary HCC
      would be necessary, pharmacological interference with EZH2 might be a promising
      therapeutic approach to targeting tumor-initiating HCC cells.

PMID- 21717454
TI  - Milk, dairy intake and risk of endometrial cancer: a 26-year follow-up.
AB  - Estrogens have a central role in the etiology of endometrial cancer. Milk and
      dairy products are a source of steroid hormones and growth factors that might
      have physiological effects in humans. We hypothesized that high intakes of milk
      and dairy products are associated with an increased risk of endometrial cancer,
      particularly among postmenopausal women not using hormone therapy. This was a
      prospective cohort study with 68,019 female participants in the Nurses' Health
      Study aged 34-59 in 1980. Milk and dairy consumption were assessed in 1980, 1984,
      1986, 1990, 1994, 1998 and 2002 as servings per day and the follow-up continued
      through 2006. The multivariate relative risks (RRs) of adenocarcinoma of the
      endometrium across categories of cumulatively averaged total dairy consumption
      compared with < 1 svg/day were: 0.94 (95% CI = 0.71-1.25) for 1-1.4 svg/day, 1.14
      (0.87-1.49) for 1.5-1.9 svg/day, 1.10 (0.84-1.44) for 2-2.9 svg/day, 1.26 (0.94
      1.70) for >= 3 svg/day (p for trend = 0.06). The association between total dairy
      intake and endometrial cancer was significant only among the postmenopausal women
      (for >= 3 svg/day RR = 1.41, 95% CI = 1.01-1.98, p for trend = 0.02) and was
      evident only among those who were not currently using hormone therapy (RR = 1.58,
      95% CI = 1.05-2.36, p for trend = 0.003). Total dairy intake was not
      significantly associated with risk of preinvasive endometrial cancer. In
      conclusion, we observed a marginally significant overall association between
      dairy intake and endometrial cancer and a stronger association among
      postmenopausal women who were not using estrogen-containing hormones.

PMID- 21717456
TI  - Absence of common activating mutations of the epidermal growth factor receptor
      gene in thyroid cancers from American and Japanese patients.

PMID- 21717457
TI  - Effects of small molecule inhibitors of PI3K/Akt/mTOR signaling on neuroblastoma
      growth in vitro and in vivo.
AB  - Activation of the PI3K/Akt signaling pathway is correlated with poor prognosis in
      neuroblastoma, the most common and deadly extracranial tumor of childhood. In
      this study, we show that the small-molecule inhibitors of phosphoinositide
      dependent protein kinase-1 (PDK1) OSU03012 and the dual class I PI3K/mTOR
      inhibitor PI103 have profound effects on neuroblastoma survival in vitro and in
      vivo. Both OSU03012 and PI103 inhibited neuroblastoma growth in vitro. In treated
      cells, OSU03012 induced apoptosis and an S phase cell cycle arrest, whereas only
      minor apoptosis was detected in PI103 treated cells together with a G1 arrest.
      Both OSU03012 and PI103 downregulated phosphorylation of Akt and inhibited the
      downstream targets glycogen synthase kinase-3beta (GSK3beta) and p70 S6 kinase-1
      (S6K1), as well as downregulated the expression of cyclin D1 and Mycn protein.
      Neuroblastoma cells expressing high levels of Mycn were more sensitive to
      OSU03012 or PI103 compared with cells expressing low Mycn levels. Both compounds
      significantly inhibited the growth of established, subcutaneous MYCN-amplified
      neuroblastoma xenografts in nude NMRI nu/nu mice. These results suggest that
      inhibition of the PI3K/Akt signaling pathway represent a clinical relevant target
      for the treatment of patients with high-risk MYCN-amplified neuroblastoma.

PMID- 21717458
TI  - Health and economic impact of HPV 16/18 vaccination and cervical cancer screening
      in Eastern Africa.
AB  - Eastern Africa has the world's highest cervical cancer incidence and mortality
      rates. We used epidemiologic data from Kenya, Mozambique, Tanzania, Uganda, and
      Zimbabwe to develop models of HPV-related infection and disease. For each
      country, we assessed HPV vaccination of girls before age 12 followed by screening
      with HPV DNA testing once, twice, or three times per lifetime (at ages 35, 40,
      45). For women over age 30, we assessed only screening (with HPV DNA testing up
      to three times per lifetime or VIA at age 35). Assuming no waning immunity, mean
      reduction in lifetime cancer risk associated with vaccination ranged from 36 to
      45%, and vaccination followed by screening once per lifetime at age 35 with HPV
      DNA testing ranged from 43 to 51%. For both younger and older women, the most
      effective screening strategy was HPV DNA testing three times per lifetime.
      Provided the cost per vaccinated girl was less than I$10 (I$2 per dose),
      vaccination had an incremental cost-effectiveness ratio [I$ (international
      dollars)/year of life saved (YLS)] less than the country-specific per capita GDP,
      a commonly cited heuristic for "very cost-effective" interventions. If the cost
      per vaccinated girl was between I$10 (I$2 per dose) and I$25 (I$5 per dose),
      vaccination followed by HPV DNA testing would save the most lives and would be
      considered good value for public health dollars. These results should be used to
      catalyze design and evaluation of HPV vaccine delivery and screening programs,
      and contribute to a dialogue on financing HPV vaccination in poor countries.

PMID- 21717459
TI  - HTLV-1 positive and negative T cells cloned from infected individuals display
      telomerase and telomere genes deregulation that predominate in activated but
      untransformed CD4+ T cells.
AB  - Untransformed HTLV-1 positive CD4(+)  cells from infected individuals are
      selected for expressing tax and displaying morphological features consistent with
      telomere dysfunctions. We show that in resting HTLV-1 positive CD4(+)  cells
      cloned from patients, hTERT expression parallels tax expression and cell cycling.
      Upon activation, these cells dramatically augment tax expression, whereas their
      increase in telomerase activity is about 20 times lower than that of their
      uninfected counterpart. Activated HTLV-1 positive CD4(+)  but not uninfected
      CD4(+)  or CD8(+)  clones also repress the transcription of TRF1, TPP1, TANK1,
      POT1, DNA-PKc and Ku80. Both infected and uninfected lymphocytes from infected
      individuals shared common telomere gene deregulations toward a pattern consistent
      with premature senescence. ATLL cells displayed the highest telomerase activity
      (TA) whereas recovered a telomere gene transcriptome close to that of normal
      CD4(+)  cells. In conclusion HTLV-1-dependent telomere modulations seem involved
      in clonal expansion, immunosuppression, tumor initiation and progression.

PMID- 21717460
TI  - Loss of p16 expression is associated with the stem cell characteristics of
      surface markers and therapeutic resistance in estrogen receptor-negative breast
      cancer.
AB  - Triple-negative breast cancer [TNBC, which is negative for the estrogen receptor
      (ER), progesterone receptor, and human epidermal growth factor receptor 2] is a
      high-risk form of the disease without a specific therapy. DNA microarray and
      immunohistochemical analyses have shown that most TNBCs fall within the basal
      like histological subset of breast cancers, which frequently exhibit inactivation
      of the retinoblastoma tumor suppressor (Rb) and upregulation of the cyclin
      dependent kinase inhibitor p16(INK4a)  (p16). However, downregulation of p16
      expression has been observed in some basal-like breast cancer cell lines,
      suggesting that such cells can be divided into two groups according to Rb and p16
      status. We now show that cells that are CD44(+)  and CD24(-) , a phenotype
      associated with stem-like breast cancer cells, are more abundant in ER(-) /p16(-)
      breast cancer cell lines than in ER(-) /p16(+)  lines. It was also found that
      p16 expression was downregulated in mammospheres from an ER-negative breast
      cancer cell line. Depletion of p16 by RNA interference in ER-negative breast
      cancer cells increased the percentage of CD44(+) /CD24(-)  cells and increased
      the expression of mRNA of the ES-like genes Nanog, Oct4, and Sox2 through an Rb
      independent pathway. Furthermore, such depletion of p16 reduced chemosensitivity.
      The loss of p16 expression may thus reduce the response of ER-negative breast
      cancer cells to chemotherapy by conferring cancer stem cell-like properties.
      Consistent with this conclusion, immunohistochemical analysis of the clinical
      samples suggests that low p16 expression in TNBC is associated with resistance to
      preoperative chemotherapy.

PMID- 21717461
TI  - PD-1 expression on Melan-A-reactive T cells increases during progression to
      metastatic disease.
AB  - Programmed death 1 (PD-1) is known as an important factor for the development of
      tolerogenicity. This has been proven in chronic viral infections and different
      tumor models. To address the role of PD-1 and its ligand programmed death ligand
      1 (PD-L1) in different stages of malignant melanoma, we investigated peripheral
      blood and tumor tissues in regard to overall survival (OS) and prognostic
      relevance. One hundred samples of peripheral blood mononuclear cells from HLA
      A2(+)  patients with malignant melanoma (Stages I-IV) were analyzed in seven
      color FACS combined with multimer analyses for the immunodominant epitope of
      Melan-A (peptide A2/Melan-A(p26-35mod) ). Corresponding formalin-fixed paraffin
      embedded tissues of primary tumor and distant organ metastases from 37 cases were
      analyzed by immunohistochemistry for Melan-A, PD-L1 and PD-1 expression. Compared
      to the total CD8(+)  T cell population, PD-1 expression by A2/Melan-A(+)  CD8(+) 
      T cells was over-represented in melanoma stages III and IV (p < 0.001). Although
      elevation of PD-1(+)  Melan-A(+)  CD8(+)  T cells had no significant influence on
      OS, a positive correlation was observed between PD-L1 expression on melanoma
      cells and OS (p = 0.05). Correlation of advanced tumor stage with increased
      A2/Melan-A-multimer(+)  PD-1(+)  T cells in the peripheral blood suggest that
      blocking of PD-1 could have therapeutic potential in advanced stage melanoma.

PMID- 21717462
TI  - Utilization of personal therapy by psychotherapists: a practice-friendly review
      and a new study.
AB  - This article offers both a practice-friendly review of research on therapists'
      personal therapy and a new study of personal psychotherapy among 3,995
      psychologists, counselors, social workers, psychiatrists, and nurses in 6 English
      speaking countries. The prevalence of personal therapy as it relates to
      professional discipline, theoretical orientation, gender, and career level are
      studied. Findings showed that 87% of the overall sample embarked on personal
      therapy at least once: 94% of analytic/psychodynamic therapists, 91% of
      humanistic therapists, 73% of cognitive-behavioral therapists, 82% of the novice
      therapists to 89% of senior therapists. Both the existing research and this new
      study demonstrate the extraordinary commonality of personal therapy among
      psychotherapists, and encourage further use for professional training, clinical
      practice, and therapist self-care.

PMID- 21717463
TI  - Whey protein-polysaccharide blended edible film formation and barrier, tensile,
      thermal and transparency properties.
AB  - BACKGROUND: Films made from different protein (P) or polysaccharide (PS)
      materials have widely different properties. The objective of this study was to
      determine whether whey protein isolate (WPI)-PS blended films possess a
      combination of properties intermediate and possibly superior to WPI or PS film
      alone. RESULTS: Oxygen permeability (OP) and tensile strength (TS) for PS-WPI
      blended films were intermediate between the OP and TS properties of pure
      methycellulose (MC), hydroxypropylmethylcellulose (HPMC) or sodium alginate (SA)
      film and pure WPI film. Starch-WPI blends gave the weakest films. Water vapor
      permeability values for all pure and blended films were similar. Blended films
      made of MC, HPMC or SA with WPI had lower transparency than pure MC, HPMC, SA or
      WPI films. Differential scanning calorimetry thermograms obtained from the
      blended films exhibited a single glass transition temperature (T(g) ) at an
      intermediate value between the T(g) values of the pure films. CONCLUSIONS:
      Whether properties of PS-WPI blended films are intermediate to properties of the
      pure PS and WPI film depends on the particular PS and specific property. In the
      case of MC or HPMC with WPI, the blended films reflect the higher TS of the PS
      and lower OP of the WPI.

PMID- 21717464
TI  - Identification of Acetobacter strains from Thai fermented rice products based on
      the 16S rRNA gene sequence and 16S-23S rRNA gene internal transcribed spacer
      restriction analyses.
AB  - BACKGROUND: Fermented rice flour (khao-khab, a non-glutinous rice) and related
      products are Thai traditional products. The types of acetic acid bacteria (AAB)
      microflora in khao-khab have not been reported. In this study, Acetobacter
      strains were isolated and identified based on the phenotypic and chemotaxonomic
      characteristics and molecular aspects. RESULTS: Twenty-five acetic acid bacteria
      isolated from fermented rice products and a starter for sweetened rice in
      Thailand by an enrichment culture approach, were assigned to the genus
      Acetobacter by phenotypic and chemotaxonomic characterisations. On the basis of
      the 16S rRNA gene sequence and 16S-23S rRNA gene ITS restriction analyses, 25
      isolates were divided into six groups and identified at the specific level: (1)
      Group 1 included five isolates, which were identified as A. indonesiensis; (2)
      Group 2 included two isolates, which were identified as A. lovaniensis; (3) Group
      3 included one isolate, which was identified as A. orientalis; (4) Group 4
      included eleven isolates, which were identified as A. pasteurianus; (5) Group 5
      included three isolates, which were identified as A. syzygii and (6) Group 6
      included three isolates, which were unidentified and considered to constitute a
      new species. CONCLUSION: Results revealed that various Acetobacter species were
      distributed in Thai fermented rice flour and related products. A novel
      Acetobacter species was isolated from the product.

PMID- 21717465
TI  - Monitoring of barley starch amylolysis by gravitational field flow fractionation
      and MALDI-TOF MS.
AB  - BACKGROUND: In barley, starch occurs in the form of granules with bimodal size
      distribution. Enzymatic hydrolysis of the starch granule is one of the most
      important reactions occurring during malting and mashing. Previous studies
      revealed the discrepancies in the assumption that barley varieties with better
      malting qualities should have a higher A/B (large/small starch granules) ratio.
      This led us to focus our attention on detailed analysis of two barley varieties,
      Jersey and Tolar, both with high malting quality but significantly differing in
      A/B (1.28 and 0.66, respectively), were chosen for more detailed analysis in the
      actual work. In this study, the capacity of gravitational field flow
      fractionation (GFFF) to monitor amylolysis of the starch granules was
      investigated. RESULTS: Isolated starch granules from these two barley cultivars
      were treated with amylases. The changes in starch granule size and bimodal
      distribution were studied by GFFF. Simultaneously, free sugars released during
      enzymatic digestion were observed by matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry. The changes in the fractogram and in the mass
      spectra reflect a correlation with the progress of enzymatic hydrolysis.
      CONCLUSION: The results show the interest in utilization of GFFF as a simple and
      cheap method for monitoring changes in the distribution of the starch granule
      size during amylolysis.

PMID- 21717466
TI  - Salt-induced modulation in inorganic nutrients, antioxidant enzymes, proline
      content and seed oil composition in safflower (Carthamus tinctorius L.).
AB  - BACKGROUND: Safflower (Carthamus tinctorius L.) has gained considerable ground as
      a potential oil-seed crop. However, its yield and oil production are adversely
      affected under saline conditions. The present study was conducted to appraise the
      influence of salt (NaCl) stress on yield, accumulation of different inorganic
      elements, free proline and activities of some key antioxidant enzymes in plant
      tissues as well as seed oil components in safflower. Two safflower accessions
      differing in salt tolerance (Safflower-33 (salt sensitive) and Safflower-39 (salt
      tolerant)) were grown under saline (150 mmol L(-1) ) conditions and salt-induced
      changes in the earlier-mentioned physiological attributes were determined.
      RESULTS: Salt stress enhanced leaf and root Na(+) , Cl(-) and proline
      accumulation and activities of leaf superoxide dismutase, catalase and
      peroxidase, while it decreased K(+) , Ca(2+) and K(+) /Ca(2+) and Ca(2+) /Na(+)
      ratios and seed yield, 100-seed weight, number of seeds, as well as capitula,
      seed oil contents and oil palmitic acid. No significant effect of salt stress was
      observed on seed oil alpha-tocopherols, stearic acid, oleic acid or linoleic acid
      contents. Of the two safflower lines, salt-sensitive Safflower-33 was higher in
      leaf and root Na(+) and Cl(-) , while Safflower-39 was higher in leaf and root
      K(+) , K(+) /Ca(2+) and Ca(2+) /Na(+) and seed yield, 100-seed weight, catalase
      activity, seed oil contents, seed oil alpha-tocopherol and palmitic acid. Other
      attributes remained almost unaffected in both accessions. CONCLUSION: Overall,
      high salt tolerance of Safflower-39 could be attributed to Na(+) and Cl(-)
      exclusion, high accumulation of K(+) and free proline, enhanced CAT activity,
      seed oil alpha-tocopherols and palmitic acid contents.

PMID- 21717467
TI  - Rapid resolution of severe neuralgic amyotrophy after treatment with
      corticosteroids and intravenous immunoglobulin.

PMID- 21717468
TI  - How soon after temporal bone fracture should we perform electroneurography?

PMID- 21717470
TI  - The value of admission HbA(1c) level in diabetic patients with acute coronary
      syndrome.
AB  - BACKGROUND: Elevated admission glucose level is a strong predictor of short-term
      adverse outcome in patients with acute coronary syndrome (ACS). However, the
      prognostic value of diabetic control (ie, hemoglobin A(1c) levels) in patients
      with ACS is still undefined. HYPOTHESIS: Hemoglobin A(1c) level may predict short
      term outcome in patients with ACS. METHODS: We conducted a retrospective study
      with prospective follow-up in 317 diabetic patients with ACS. Patients were
      stratified into 2 groups based on HbA(1c) level, checked within 8 weeks of the
      index admission (optimal control group, HbA(1c) <=7%; suboptimal control group,
      HbA(1c) >7%). All patients were followed up prospectively for major adverse
      cardiovascular events (MACE) and mortality for 6 months. Short-term clinical
      outcomes were also compared between the 2 study groups. RESULTS: In our cohort,
      27.4%, 46.4%, and 26.2% patients had unstable angina, non-ST-segment elevation
      myocardial infarction, and ST-segment elevation myocardial infarction,
      respectively. In-hospital mortality was similar in both HbA(1c) groups (3.37% vs
      2.88%, P = 0.803). Six-month MACE was also similar (26.40% vs 26.47%, P = 0.919).
      All-cause mortality, cardiovascular mortality, symptom-driven revascularization,
      rehospitalization for angina, and hospitalization for heart failure were also
      similar in both groups. The hazard ratios for 6-month MACE and individual
      endpoints were also similar in both groups. CONCLUSIONS: This study suggests that
      HbA(1c) levels before admission are not associated with short-term cardiovascular
      outcome in diabetic patients subsequently admitted with ACS.

PMID- 21717471
TI  - Right ventricular systolic pressure assessed by echocardiography: a predictive
      factor of mortality in patients with scleroderma.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a well-known complication of
      systemic sclerosis (SSc). Doppler echocardiographic screening for the detection
      of PAH (by measuring right ventricular systolic pressure [RVSP]) is therefore
      recommended for all patients with SSc. However, the validity of RVSP as a
      predictor of mortality in patients with SSc is not well established. HYPOTHESIS:
      Doppler-determined PAH identifies a high-risk subset of patients with SSc with
      decreased survival. METHODS: We performed echocardiography in 155 consecutive
      patients with SSc between May 2005 and July 2006 and tested the value of an RVSP
      level of >=36 mm Hg to predict mortality. Cox proportional hazards model was used
      to examine the individual relationship between each variable and the mortality
      rate. RESULTS: Tricuspid regurgitant jets for RVSP determination were quantified
      in 129 patients (82.6%), of which 47 (36.4%) had RVSP >=36 mm Hg. The median
      follow-up time was 34 months. The 1-, 2-, and 3-year survival rates were
      significantly lower among SSc patients with RVSP >=36 vs <=36 mm Hg (82%, 78%,
      and 67% vs 98%, 90%, and 86%, respectively, P < 0.01 by Wilcoxon test). In a
      multivariate analysis including echocardiographic and clinical variables, only an
      RVSP >=36 mm Hg and a New York Heart Association III/IV class were associated
      with increased mortality; the respective Cox hazard ratios were 2.22 (95%
      confidence interval [CI]: 1.01-4.89, P = 0.048) and 4.77 (95% CI: 2.09-10.90, P =
      0.000). CONCLUSIONS: Our results indicate that Doppler RVSP identifies a high
      risk subset and supports the use of Doppler RVSP as a screening test in patients
      with SSc who may warrant early treatment of their PAH.

PMID- 21717472
TI  - Electrocardiogram-based predictors of sudden cardiac death in patients with
      coronary artery disease.
AB  - Current recommendations on which patients with coronary artery disease (CAD)
      should be offered an implantable cardioverter defibrillator for the primary
      prevention of sudden cardiac death (SCD) rely heavily on the presence of
      depressed left ventricular ejection fraction. Because the majority of SCD victims
      with CAD have preserved left ventricular function, additional cardiac
      investigations are likely to play an increasing role in the risk stratification
      of CAD patients. A number of studies have demonstrated that certain parameters on
      the traditional 12-lead electrocardiogram (ECG) and other ECG-based
      investigations (such as signal-averaged ECG, heart rate turbulence, T-wave
      alternans) can provide important information on the underlying cardiac substrate
      abnormality that may predispose to ventricular arrhythmias and SCD. This article
      reviews some of the evidence for these ECG-based tests as predictors of SCD in
      patients with CAD and addresses their advantages and limitations.

PMID- 21717473
TI  - Peripheral arterial disease--what do we need to know?
AB  - Peripheral artery disease (PAD) results from progressive narrowing of arteries
      secondary to atherosclerosis and is defined as an Ankle Brachial Index of <0.9.
      PAD is highly prevalent and is an increasing burden on both the economy and the
      patient, especially given the rapid shift in demographics in the United States.
      Despite its prevalence and association with cardiovascular disease, PAD is still
      underdiagnosed and undertreated. This may, in part, be related to lack of
      recognition from the physician's side or paucity of evidence from clinical
      trials. It has been shown that medical therapy approved for cardiovascular
      disease is effective in the treatment of PAD and decreases cardiovascular events.
      Various revascularization strategies are also available for improving symptoms
      and quality of life in these patients, yet they are underutilized. In an attempt
      to increase its recognition, PAD has been considered a coronary artery disease
      equivalent. This article reviews the diagnosis and management of PAD. (c) 2011
      Wiley Periodicals, Inc. The authors have no funding, financial relationships, or
      conflicts of interest to disclose.

PMID- 21717474
TI  - Outcome of contemporary percutaneous coronary intervention in the elderly and the
      very elderly: insights from the Blue Cross Blue Shield of Michigan Cardiovascular
      Consortium.
AB  - BACKGROUND: There is a paucity of data on the outcome of contemporary
      percutaneous coronary intervention (PCI) in the elderly. Accordingly, we assessed
      the impact of age on outcome of a large cohort of patients undergoing PCI in a
      regional collaborative registry. HYPOTHESIS: Increasing age is associated with a
      higher incidence of procedural-related complications. METHODS: We evaluated the
      outcome of 152,373 patients who underwent PCI from 2003 to 2008 in the 31
      hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular
      Consortium. The procedural outcomes of the cohort were compared by dividing
      patients into < 70 years of age, 70 to 79 years, 80 to 84 years, 85 to 89 years,
      and >= 90 years. RESULTS: Of the cohort, 64.64% were <70 years of age, 23.83%
      were 70 to 79 years, 7.85% were 80 to 84 years, 3.09% were 85 to 89 years, and
      0.58% were 90 years or older. Increasing age was associated with an increase in
      all-cause in-hospital mortality, contrast-induced nephropathy, transfusion,
      stroke/transient ischemic attack, and vascular complications. The overall in
      hospital mortality rate was 1.09% and increased from 0.67% in those younger than
      70 years up to 5.44% in those 90 years old or greater. The mortality rate in
      patients over 80 years approached 12% to 15% for those with ST-segment myocardial
      infarction and 39% in cardiogenic shock patients. CONCLUSIONS: The proportion of
      elderly patients referred for PCI is increasing. Procedural complications
      increase with age, and patients presenting with unstable symptoms are at the
      highest risk.

PMID- 21717475
TI  - Clopidogrel with proton pump inhibitors: safe or not?
AB  - Gastrointestinal (GI) bleeding is a serious complication associated with use of
      antiplatelet therapy, and proton pump inhibitors (PPIs) are known to be
      beneficial in decreasing such risk. Several studies in the recent past have
      suggested concerns regarding interaction between clopidogrel and PPIs, presumably
      due to inhibition of clopidogrel activity and thus attenuation of its
      antiplatelet activity. A web-based literature and guidelines search was done
      using the keywords "clopidogrel," "omeprazole," "proton pump inhibitors" and
      "interaction." Of the available results, relevant studies (n = 11) were then
      systematically reviewed and summarized. The studies were categorized based on
      their retrospective or prospective nature. Most of the retrospective,
      observational studies suggested a link between the 2; however, recent prospective
      studies have shown no interaction, as well as a positive influence of PPIs in
      preventing the GI side effects of antiplatelet therapy. There is currently
      insufficient clinical evidence to suggest interaction between clopidogrel and
      PPIs and decision to add PPI therapy to clopidogrel should be guided by its
      clinical indications rather than as a routine prophylactic measure.

PMID- 21717476
TI  - Reaction rate of propene pyrolysis.
AB  - The reaction rate of propene pyrolysis was investigated based on the elementary
      reactions proposed in Qu et al., J Comput Chem 2009, 31, 1421. The overall
      reaction rate was developed with the steady-state approximation and the rate
      constants of the elementary reactions were determined with the variational
      transition state theory. For the elementary reaction having transition state, the
      vibrational frequencies of the selected points along the minimum energy path were
      calculated with density functional theory at B3PW91/6-311G(d,p) level and the
      energies were improved with the accurate model chemistry method G3(MP2). For the
      elementary reaction without transition state, the frequencies were calculated
      with CASSCF/6-311G(d,p) and the energies were refined with the multireference
      configuration interaction method MRCISD/6-311G(d,p). The rate constants were
      evaluated within 200-2000 K and the fitted three-parameter expressions were
      obtained. The results are consistent with those in the literatures in most cases.
      For the overall rate, it was found that the logarithm of the rate and the
      reciprocal temperature have excellent linear relationship above 400 K, predicting
      that the rate follows a typical first-order law at high temperatures of 800-2000
      K, which is also consistent with the experiments. The apparent activation energy
      in 800-2000 K is 317.3 kJ/mol from the potential energy surface of zero Kelvin.
      This value is comparable with the energy barriers, 365.4 and 403.7 kJ/mol, of the
      rate control steps. However, the apparent activation energy, 215.7 kJ/mol,
      developed with the Gibbs free energy surface at 1200 K is consistent with the
      most recent experimental result 201.9 +/- 0.6 kJ/mol.

PMID- 21717477
TI  - Discrepancy in the near-solute electric dipole moment calculated from the
      electric field.
AB  - The electric dipole moment p(r) was computed as the integral of the permanent
      dipole moment of the solvent molecule MU(r) weighted by the orientational
      probability distribution Omega(r;O) over all orientations, where O is the
      orientation of the solvent molecule at r. The relationship between Omega(r;O) and
      the potential of the mean torque was derived; p(r) is proportional to the
      electric field E(r) under the following assumptions: (1) the van der Waals (vdW)
      interaction is independent of the orientation of the solvent molecule at r; (2)
      the solvent molecule and its electrical effect are modeled as a point dipole
      moment; (3) the solvent molecule at r is in a region far from the solute; and (4)
      MUE(r) ? k(B) T, where k(B) is Boltzmann's constant and T is absolute
      temperature. The errors caused by calculating near-solute Omega(r) and p(r) from
      E(r) are unclear. The results show that Omega(r) is inconsistent with the value
      calculated from E(r) for water molecules in the first and second shells of solute
      with charge state Q = +/-1 e, and a large variation in solvent molecular
      polarizability gamma(mol) (r), which appeared in the first valley of 4pir(2) E(r)
      for |Q| < 1 e. Nonetheless, p(r) is consistent with the values calculated from
      E(r) for |Q| <= 1 e. The implication is that the assumptions for calculating p(r)
      can be ignored in the calculation of the solvation free energy of biomolecules,
      as they pertain to protein folding and protein-protein/ligand interactions.

PMID- 21717478
TI  - Molecular modeling study of checkpoint kinase 1 inhibitors by multiple docking
      strategies and prime/MM-GBSA calculation.
AB  - Developing chemicals that inhibit checkpoint kinase 1 (Chk1) is a promising
      adjuvant therapeutic to improve the efficacy and selectivity of DNA-targeting
      agents. Reliable prediction of binding-free energy and binding affinity of Chk1
      inhibitors can provide a guide for rational drug design. In this study, multiple
      docking strategies and Prime/Molecular Mechanics Generalized Born Surface Area
      (Prime/MM-GBSA) calculation were applied to predict the binding mode and free
      energy for a series of benzoisoquinolinones as Chk1 inhibitors. Reliable docking
      results were obtained using induced-fit docking and quantum mechanics/molecular
      mechanics (QM/MM) docking, which showed superior performance on both ligand
      binding pose and docking score accuracy to the rigid-receptor docking. Then, the
      Prime/MM-GBSA method based on the docking complex was used to predict the binding
      free energy. The combined use of QM/MM docking and Prime/MM-GBSA method could
      give a high correlation between the predicted binding-free energy and
      experimentally determined pIC(50) . The molecular docking combined with Prime/MM
      GBSA simulation can not only be used to rapidly and accurately predict the
      binding-free energy of novel Chk1 inhibitors but also provide a novel strategy
      for lead discovery and optimization targeting Chk1.

PMID- 21717479
TI  - DockoMatic: automated peptide analog creation for high throughput virtual
      screening.
AB  - The purpose of this manuscript is threefold: (1) to describe an update to
      DockoMatic that allows the user to generate cyclic peptide analog structure files
      based on protein database (pdb) files, (2) to test the accuracy of the peptide
      analog structure generation utility, and (3) to evaluate the high throughput
      capacity of DockoMatic. The DockoMatic graphical user interface interfaces with
      the software program Treepack to create user defined peptide analogs. To validate
      this approach, DockoMatic produced cyclic peptide analogs were tested for three
      dimensional structure consistency and binding affinity against four
      experimentally determined peptide structure files available in the Research
      Collaboratory for Structural Bioinformatics database. The peptides used to
      evaluate this new functionality were alpha-conotoxins ImI, PnIA, and their
      published analogs. Peptide analogs were generated by DockoMatic and tested for
      their ability to bind to X-ray crystal structure models of the acetylcholine
      binding protein originating from Aplysia californica. The results, consisting of
      more than 300 simulations, demonstrate that DockoMatic predicts the binding
      energy of peptide structures to within 3.5 kcal mol(-1), and the orientation of
      bound ligand compares to within 1.8 A root mean square deviation for ligand
      structures as compared to experimental data. Evaluation of high throughput
      virtual screening capacity demonstrated that Dockomatic can collect, evaluate,
      and summarize the output of 10,000 AutoDock jobs in less than 2 hours of
      computational time, while 100,000 jobs requires approximately 15 hours and
      1,000,000 jobs is estimated to take up to a week.

PMID- 21717480
TI  - Molecular dynamics simulation reveals structural and thermodynamic features of
      kinase activation by cancer mutations within the epidermal growth factor
      receptor.
AB  - The epidermal growth factor receptor (EGFR) is a major target for drugs in
      treating lung carcinoma as it promotes cell growth and tumor progression.
      Structural studies have demonstrated that EGFR exists in an equilibrium between
      catalytically active and inactive forms, and dramatic conformational transitions
      occur during its activation. It is known that EGFR mutations promote such
      conformational changes that affect its activation and drug efficacy. The most
      common point mutation in lung cancer patients is a leucine to arginine
      substitution at amino acid 834 (L834R). In a recent article, we have studied
      changes in drug binding affinities due to cancer mutations of EGFR using ensemble
      molecular dynamics (MD) simulations. Here, we address an enhanced activation
      mechanism thought to be associated with this mutation. Using extended timescale
      MD simulations, the structural and energetic properties are studied for both
      active and inactive conformations of EGFR. The thermodynamic stabilities of these
      two conformations are characterized by free energy landscapes estimated from
      molecular mechanics/Poisson-Boltzmann solvent area calculations. Our study
      reveals that the L834R mutation introduces conformational changes in both states,
      adjusting the relative stabilities of active and inactive conformations and hence
      the activation of the EGFR kinase.

PMID- 21717481
TI  - The effect of polarization on multiple hydrogen-bond formation in models of self
      assembling materials.
AB  - We report density functional theory calculations at the B3LYP/D95(d,p) level on
      several different cyclic H-bonding dimers, where the monomers of each are
      connected by a pair of N-H...O=C H-bonding interactions, and the H-bonding donors
      and acceptors on each monomer are separated by polarizable spacers. Depending on
      the structures, the individual H-bonds vary in strength (enthalpy) by over a
      factor of four, from 2.41 to 10.99 kcal/mol. We attribute most of the variation
      in interaction energies to differences in the extent of polarization due to each
      of the H-bonds, which can either combine constructively or destructively. The
      dipole-dipole interactions between the pair of H-bonds also contribute somewhat
      to the relative stabilities. The relevance of these results to the design of self
      assembling materials is discussed.

PMID- 21717482
TI  - Risks, trust and knowledge: determinants of pregnant women's decisions regarding
      participation in a future Q fever screening and treatment program during a large
      epidemic in The Netherlands.
AB  - OBJECTIVE: Contracting Q fever during pregnancy carries a risk of developing
      obstetric complications. The aim of this study was to gain insight into pregnant
      women's decisions regarding participation in a future Q fever screening and
      treatment program. METHODS: Pregnant women (N = 148) in Q fever high-risk areas
      in The Netherlands were recruited via midwives' practices and via an online panel
      for a cross-sectional questionnaire survey. The outcome measures included
      intention to participate in the program, Q fever exposure risk, perceived Q fever
      risk, trust in health professionals and authorities, disease-related knowledge
      and additional outcome measures. RESULTS: Fifty-six percent of the respondents
      intended to participate in the screening and treatment program. The sole
      determinant of a higher intended program uptake was a more positive appraisal of
      program efficacy and convenience. This appraisal was in turn associated with
      perceived risk and knowledge. CONCLUSION: Women's appraisal of program efficacy
      and convenience, their disease-related knowledge and perceived Q fever risk seem
      to be crucial for their intended program uptake. A successful implementation of a
      Q fever screening and treatment program may thus depend on the benefits and
      downsides of the program, and on securing that women are aware of the risks of
      the disease.

PMID- 21717483
TI  - First trimester screening for intra-uterine growth restriction and early-onset
      pre-eclampsia.
AB  - OBJECTIVE: To assess first trimester placental growth factor (PlGF) and pregnancy
      associated plasma protein-A (PAPP-A) as screening markers for early-onset pre
      eclampsia (PE) and intra-uterine growth restriction (IUGR). METHODS: PlGF
      concentration was retrospectively measured in first trimester serum specimens of
      23 cases of early-onset PE (<34 weeks), 26 cases of IUGR (birth weight < 5th
      centile) and 5 controls per case. Levels were adjusted for gestational age (GA),
      ethnicity and smoking to obtain multiples of the expected median (MoM). Logistic
      regression was used to assess PlGF, PAPP-A and maternal characteristics as
      potential predictors of early-onset PE and IUGR. RESULTS: PlGF MoM levels were
      significantly lower in the early-onset PE group (P < 0.0001) compared with
      controls, but not in the IUGR group. PAPP-A MoM levels were significantly lower
      in the IUGR group (P < 0.01) compared with controls but not in the early-onset PE
      group. PlGF significantly improved the ability of systolic blood pressure at the
      first prenatal visit to predict early-onset PE [achieving a receiver-operating
      characteristics curve with area under the curve (AUC) of 0.8]. Combining systolic
      blood pressure at the first prenatal visit and PlGF did not significantly improve
      the predictive ability compared with PlGF alone (AUC = 0.83). CONCLUSION: Serum
      PlGF is an acceptable marker in first trimester screening for early-onset PE, but
      a poor marker in screening for IUGR. Screening performance of serum PAPP-A is
      poor for both early-onset PE and IUGR.

PMID- 21717484
TI  - Fragile X analysis of 1112 prenatal samples from 1991 to 2010.
AB  - OBJECTIVE: To determine risks of expansion for normal, intermediate, and
      premutation FMR1 CGG repeats. METHODS: PCR was used to compare the FMR1 alleles
      in prenatal (chorionic villi and amniocytes) and parental samples collected from
      1991 to 2010. Prenatal diagnoses were confirmed by Southern analysis. RESULTS:
      Fragile X analysis of 1112 pregnancies identified 558 normal, 106 intermediate,
      216 premutation, and 232 full mutation fetuses. Of 509 maternal, intermediate,
      and premutation alleles, 350 (68.7%) were unstable on transmission with
      expansions ranging from one repeat to the full mutation. The smallest premutation
      alleles expanding to the full mutation were in mothers with 65 and 66 repeats.
      Transmissions from women with or without a family history of fragile X suggested
      greater instability in women from families that included full mutation
      expansions. CONCLUSIONS: The maternal transmissions of alleles with 55 to 59 CGG
      repeats summarized here indicate that the risk for expansion to full mutation is
      substantially less than previous estimates for this size category. Most
      premutation alleles with no family history of fragile X exhibited less
      instability than those with a history of fragile X. Thus, lower risk estimates
      for full mutation expansion may be appropriate for women newly identified as
      premutation carriers through routine screening.

PMID- 21717485
TI  - Pharmacokinetic study of two acetylcholinesterase reactivators, trimedoxime and
      newly synthesized oxime K027, in rat plasma.
AB  - K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-propane
      dibromide] is a promising new reactivator of organophosphate- or
      organophosphonate-inhibited acetylcholinesterase (AChE) with low acute toxicity
      and broad spectrum efficacy. The aim of the present study was to compare the
      pharmacokinetics of both compounds. Male Wistar rats (body weight = 320 +/- 10 g)
      were administered a single intramuscular dose of K027 (22.07 mg kg(-1)) and an
      equimolar dose of trimedoxime. Blood was collected at various time intervals
      until 180 min. Plasma samples were analyzed by reversed-phase HPLC with
      ultraviolet (UV) detection. The recovery of both oximes from the plasma was
      approximately 90% and a linear relationship (R(2) > 0.998) was observed between
      the peak areas and concentrations of calibrated standards in the range 1-100 ug
      ml(-1). Near-identical plasma profiles were obtained for both compounds. No
      differences were found in the mean +/- SD values of C(max) (18.6 +/- 2.5 vs 20.0
      +/- 6.3 ug ml(-1), P = 0.72) and AUC(0-180min) (2290 +/- 304 vs 2269 +/- 197 min
      ug ml(-1), P = 0.84). However, the percentage coefficient of variation of the
      first-order rate constant of absorption (k(a)) was 3-fold higher (P < 0.01)
      providing evidence for more erratic absorption of intramuscular trimedoxime as
      compared with K027. In conclusion, oxime K027 might have superior pK properties
      that may be translated in its faster absorption and subsequent tissue
      distribution.

PMID- 21717486
TI  - Nandrolone androgenic hormone presents genotoxic effects in different cells of
      mice.
AB  - Nandrolone is an androgenic-anabolic steroid (AAS) with diverse medical
      applications but taken indiscriminately by some to rapidly increase muscle mass.
      The aim of this study was to evaluate the genotoxic and clastogenic potential of
      nandrolone (deca-durabolin(r)) in vivo in different cells of mice, using the
      comet assay and micronucleus test, respectively. The animals received
      subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg
      1 body weight). Cytotoxicity was assessed by scoring 200 consecutive total
      polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE-NCE ratio). The
      results showed a significant dose-related increase in the frequency of DNA damage
      in leukocytes, liver, bone marrow, brain and testicle cells at the three tested
      doses and a significant increase of the micronucleated polychromatic erythrocytes
      at all tested doses. Under our experimental conditions, the nandrolone steroid
      hormone showed genotoxic and clastogenic effects when administered subcutaneously
      to mice.

PMID- 21717487
TI  - Proteolytic processing of the p75 neurotrophin receptor: A prerequisite for
      signalling?: Neuronal life, growth and death signalling are crucially regulated
      by intra-membrane proteolysis and trafficking of p75(NTR).
AB  - The common neurotrophin receptor (p75(NTR) ) regulates various functions in the
      developing and adult nervous system. Cell survival, cell death, axonal and growth
      cone retraction, and regulation of the cell cycle can be regulated by p75(NTR) 
      mediated signals following activation by either mature or pro-neurotrophins and
      in combination with various co-receptors, including Trk receptors and sortilin.
      Here, we review the known functions of p75(NTR) by cell type, receptor-ligand
      combination, and whether regulated intra-membrane proteolysis of p75(NTR) is
      required for signalling. We highlight that the generation of the intracellular
      domain fragment of p75(NTR) is associated with many of the receptor functions,
      regardless of its ligand and co-receptor interactions.

PMID- 21717488
TI  - Internalized weight bias in obese patients with binge eating disorder:
      associations with eating disturbances and psychological functioning.
AB  - OBJECTIVE: Widespread bias against obese individuals may lead to the
      internalization of weight bias in obese persons. This study examined correlates
      of internalized weight bias (IWB) in obese patients with binge eating disorder
      (BED). METHOD: One hundred treatment-seeking obese patients with BED were
      administered with the eating disorders examination interview and questionnaires
      assessing IWB, fat phobia, depression, and self-esteem. RESULTS: The mean IWB
      score in this group of patients with BED was significantly greater than the mean
      IWB score observed previously in a community sample of overweight adults. IWB was
      positively associated with eating disorder psychopathology, fat phobia, and
      depression, and negatively associated with self-esteem. IWB made significant
      independent contributions to the variance in eating disorder psychopathology even
      after accounting for fat phobia, depression, and self-esteem. DISCUSSION:
      Treatment-seeking obese patients with BED demonstrate high levels of IWB. IWB may
      contribute to the variance in eating disorder psychopathology in BED patients,
      beyond the contributions of fat phobia, depression, and self-esteem.

PMID- 21717489
TI  - The impact of selection bias on test decisions in randomized clinical trials.
AB  - Selection bias affects the evaluation of clinical trials, for example, by
      elevating type I error rate. We investigated the effect of selection bias on type
      I error rate considering permuted block randomization. We also considered
      stratified randomization in general and for the special case of multicenter
      clinical trials, where we incorporated preferences of the investigator in our
      approach. Finally, the effect of underrunning is modeled, that is, where the
      randomization list exceeds the actual number of patients taking part in the
      trial. For all situations, we illustrate and discuss the impact of selection bias
      on type I error rate.

PMID- 21717490
TI  - Dynamic clustering detection through multi-valued descriptors of dermoscopic
      images.
AB  - This paper introduces a dynamic clustering methodology based on multi-valued
      descriptors of dermoscopic images. The main idea is to support medical diagnosis
      to decide if pigmented skin lesions belonging to an uncertain set are nearer to
      malignant melanoma or to benign nevi. Melanoma is the most deadly skin cancer,
      and early diagnosis is a current challenge for clinicians. Most data analysis
      algorithms for skin lesions discrimination focus on segmentation and extraction
      of features of categorical or numerical type. As an alternative approach, this
      paper introduces two new concepts: first, it considers multi-valued data that
      scalar variables not only describe but also intervals or histogram variables;
      second, it introduces a dynamic clustering method based on Wasserstein distance
      to compare multi-valued data. The overall strategy of analysis can be summarized
      into the following steps: first, a segmentation of dermoscopic images allows to
      identify a set of multi-valued descriptors; second, we performed a discriminant
      analysis on a set of images where there is an a priori classification so that it
      is possible to detect which features discriminate the benign and malignant
      lesions; and third, we performed the proposed dynamic clustering method on the
      uncertain cases, which need to be associated to one of the two previously
      mentioned groups. Results based on clinical data show that the grading of
      specific descriptors associated to dermoscopic characteristics provides a novel
      way to characterize uncertain lesions that can help the dermatologist's
      diagnosis.

PMID- 21717491
TI  - Bayesian methods for fitting mixture models that characterize branching tree
      processes: An application to development of resistant TB strains.
AB  - For pathogens that must be treated with combinations of antibiotics and acquire
      resistance through genetic mutation, knowledge of the order in which drug
      resistance mutations occur may be important for determining treatment policies.
      Diagnostic specimens collected from patients are often available; this makes it
      possible to determine the presence of individual drug resistance-conferring
      mutations and combinations of these mutations. In most cases, these specimens are
      only available from a patient at a single point in time; it is very rare to have
      access to multiple specimens from a single patient collected over time as
      resistance accumulates to multiple drugs. Statistical methods that use branching
      trees have been successfully applied to such cross-sectional data to make
      inference on the ordering of events that occurred prior to sampling. Here, we
      propose a Bayesian approach to fitting branching tree models that has several
      advantages, including the ability to accommodate prior information regarding
      measurement error or cross resistance and the natural way it permits the
      characterization of uncertainty. Our methods are applied to a data set for drug
      resistant TB in Peru; the goal of the analysis was to determine the order with
      which patients develop resistance to the drugs commonly used for treating TB in
      this setting.

PMID- 21717494
TI  - Approximate nonparametric corrected-score method for joint modeling of survival
      and longitudinal data measured with error.
AB  - We consider the problem of jointly modeling survival time and longitudinal data
      subject to measurement error. The survival times are modeled through the
      proportional hazards model and a random effects model is assumed for the
      longitudinal covariate process. Under this framework, we propose an approximate
      nonparametric corrected-score estimator for the parameter, which describes the
      association between the time-to-event and the longitudinal covariate. The term
      nonparametric refers to the fact that assumptions regarding the distribution of
      the random effects and that of the measurement error are unnecessary. The finite
      sample size performance of the approximate nonparametric corrected-score
      estimator is examined through simulation studies and its asymptotic properties
      are also developed. Furthermore, the proposed estimator and some existing
      estimators are applied to real data from an AIDS clinical trial.

PMID- 21717495
TI  - Assessing bioequivalence of generic antiepilepsy drugs.
AB  - OBJECTIVE: Patients with epilepsy are often concerned that switching between
      brand-name and generic formulations of antiepilepsy drugs (AEDs) may cause
      clinically significant changes in plasma drug concentrations. We assessed
      bioequivalence (BE) studies for approved generic AEDs to evaluate US Food and
      Drug Administration claims that: (1) generic AEDs are accurate copies of
      reference formulations; (2) delivery of reference formulations may be as variable
      as generic AEDs and so provide no increased benefit; and (3) switches between
      generic AED formulations are safe and effective. METHODS: We determined
      differences in 90% confidence interval limits for total drug exposure (AUC(0-t) )
      and peak concentration (Cmax) ratios of generic and reference formulations during
      fasting and fed BE studies. We simulated BE between generic formulations after
      adjusting for reference values. RESULTS: AUC(0-t) values of approved reference
      and generic formulations differed by <15% in 99% of BE studies; Cmax differed by
      <15% in 89% of studies. Food affected variability of Cmax but not AUC(0-t) .
      Intersubject variability in Cmax and AUC(0-t) was small and similar for reference
      and generic products. In simulated switches between 595 pairs of generic AED
      formulations, estimated AUC(0-t) differed by >15% for 17% of pairs; estimated
      Cmax differed by >15% for 39%. AEDs with low bioavailability and solubility (eg,
      oxcarbazepine) had the greatest variability in BE. INTERPRETATION: Most generic
      AED products provide total drug delivery (AUC) similar to reference products;
      differences in peak concentrations between formulations are more common. Switches
      between generic AED products may cause greater changes in plasma drug
      concentrations than generic substitutions of reference products.

PMID- 21717496
TI  - Exogenously administered bombesin and gastrin releasing peptide contract the
      female rat urethra in vivo and in vitro.
AB  - BACKGROUND: Bombesin (BOM) and gastrin releasing peptide (GRP) have been located
      to the lower urinary tract (LUT). However, there is a paucity of data
      demonstrating the impact of these endogenous peptides. OBJECTIVES: The aim of the
      present study was to investigate the contractile actions of BOM and GRP on the
      female rat urethra in vitro and in vivo. Female Sprague-Dawley rats (n = 37)
      weighing approximately 225 g were used. Intraurethral pressure was recorded by a
      catheter placed at the maximum pressure zone corresponding to the intrinsic
      urethral sphincter. MEASUREMENTS: In vitro, changes in intraurethral pressure was
      conducted on perfused intact urethral/bladder preparations and are expressed as
      percentages of sphincteric intraurethral pressure achieved with noradrenaline. In
      vivo, changes in intraurethral pressure was conducted in anesthetized subjects
      and compared with the baseline intraurethral pressure and sham controls. RESULTS:
      In vitro, the increase in intraurethral pressure induced by BOM was 23.6 +/- 3.2
      cmH(2)O, exceeding the pressure evoked with NA by 9.6 cmH(2) O or 174.4% whereas
      GRP induced a maximum pressure of 10.7 +/- 1.6 cmH(2) O, an increase of 2.2 +/-
      0.5 cmH(2) O or 82.9% (P < 0.05) of the NA evoked pressure. In vivo, the mean
      baseline pressure was 22.9 +/- 1.4 cmH(2) O. The intraurethral pressure evoked by
      BOM was 50.6 +/- 6.3 cmH(2) O (P < 0.05), and for GRP, the evoked intraurethral
      pressure was 56.2 +/- 13.4 cmH(2) O (P < 0.05). CONCLUSIONS: The present data
      suggest that both BOM and GRP may contribute to the control of continence by
      their contractile action on the sphincters of the LUT outflow region.

PMID- 21717497
TI  - Re: variability of urodynamic parameters in patients with overactive bladder.
      Neurourol Urodyn 2011;30:1570-1674.

PMID- 21717498
TI  - Comparison of two methods for measuring the pubococcygeal line from sagittal
      plane magnetic resonance imaging.
AB  - AIMS: The pubococcygeal line (PCL) is an important reference line for determining
      measures of pelvic organ support on sagittal-plane magnetic resonance imaging
      (MRI); however, there is no consensus on where to place the posterior point of
      the PCL. As coccyx movement produced during pelvic floor muscle (PFM)
      contractions may affect other measures, optimal placement of the posterior point
      is important. This study compared two methods for measuring the PCL, with
      different posterior points, on T2-weighted sagittal MRI to determine the effect
      of coccygeal movement on measures of pelvic organ support in older women.
      METHODS: MRI of the pelvis was performed in the midsagittal plane, at rest and
      during PFM contractions, on 47 community-dwelling women 60 and over. The first
      PCL was measured to the tip of the coccyx (PCLtip) and the second to the
      sacrococcygeal joint (PCLjnt). Four measures of pelvic organ support were made
      using each PCL as the reference line: urethrovesical junction height,
      uterovaginal junction height, M-line and levator plate angle. RESULTS: During the
      PFM contraction the PCLtip shortened and lifted (P < 0.001); the PCLjnt did not
      change (P > 0.05). The changes in the four measures of pelvic organ support were
      smaller when measured relative to the PCLtip as compared to those to the PCLjnt
      (P < 0.001). CONCLUSIONS: Coccyx movement affected the length and position of the
      PCLtip, which resulted in underestimates of the pelvic-organ lift produced by the
      PFM contraction. Therefore, we recommend that the PCL be measured to the
      sacrococcygeal joint and not to the tip of the coccyx.

PMID- 21717499
TI  - Exogenously administered bombesin and gastrin releasing peptide contract the
      female rat urethra in vivo and in vitro.
AB  - BACKGROUND: Bombesin (BOM) and gastrin releasing peptide (GRP) have been located
      to the lower urinary tract. However, there is a paucity of data demonstrating the
      impact of these neuropeptides. OBJECTIVES: The present study investigates the
      impact of BOM and GRP in the female Sprague-Dawley rats 225  g b.w. n = 37
      urethras in vitro and in vivo. Intraurethral pressure was recorded by a catheter
      placed at the maximum pressure zone corresponding to the intrinsic urethral
      spincter. MEASUREMENTS: In vitro, the intraurethral pressure was measured in
      response to the administration of BOM and GRP and noradrenaline from perfused
      intact urethral/bladder preparations. In vivo, changes in intraurethral pressure
      were conducted in anesthetized subjects and compared with the basal intraurethral
      pressure and sham controls. RESULTS: In vitro, the increase in intraurethral
      pressure induced by BOM was 23.6 +/- 3.2  cmH(2) O, exceeding the pressure evoked
      with NA by 10.7  cmH(2) O whereas GRP induced 10.7 +/- 1.6  cmH(2) O, an increase
      of 3.3 cmH(2) O but less than the NA evoked intraurethral pressure by 2.2  cmH(2)
      O. Incubation with scopolamine (1 uM), phentolamine (1  uM), pancuronium (1  uM),
      and indomethacin (1  uM) did not produce any significant difference in the
      contractile responses to BOM or GRP. In vivo, the mean basal pressure was 22.9 +/
      1.4  cmH(2) O. The intraurethral pressure evoked by BOM was 29.7  cmH(2) O (21.3
      +/-  1.3 to 51.0  +/-  1.6  cmH(2) O), and for GRP, the evoked intraurethral
      pressure was 33.8  cmH(2) O (22.3  +/-  1.9 to 56.2  +/-  30  cmH(2) O).
      CONCLUSIONS: BOM and GRP may contribute to the control of continence by their
      contractile action on the sphincters of the lower urinary tract outflow region.

PMID- 21717500
TI  - Consecutive vesicovaginal fistula for transobturator sling perforations and
      successful repairs with skin flap.
AB  - AIM: To report a reconstructive technique of large vesicovaginal fistula repairs,
      which is a rare complication of the most modern anti-incontinence procedures
      (tension-free tapes) using the "oldie but goodie" Lehoczky's island flap.
      METHODS: Women with large vesicovaginal fistulas caused by mid-urethral
      transobturator tape were operated in our department. The transobturator tape was
      removed and the large fistula was closed using the skin island flap. The flap was
      created from the regional skin and subcutaneous tissue and pulled with intact
      vascular supply through a paravaginal tunnel to the site of the vaginal defect.
      RESULTS: No complications occurred after the reconstructions. The patients have
      become permanently continent and free from fistulas. CONCLUSIONS: Mid-urethral
      transobturator sling is a successful procedure evidenced worldwide with a very
      low rate of fistula formation. Lehoczky's island flap can be a reasonable and
      safe surgical option in the repair of large defects of the vaginal wall.

PMID- 21717501
TI  - Reduction of urgency severity is associated with long-term therapeutic effect
      after intravesical onabotulinumtoxin A injection for idiopathic detrusor
      overactivity.
AB  - AIMS: Intravesical onabotulinumtoxin A (BoNT-A) injection is a promising
      treatment for refractory detrusor overactivity (DO). This study investigated the
      long-term success rate of BoNT-A injection for patients with idiopathic DO and
      its association with reduction of urgency severity. METHODS: This study was a
      retrospective analysis of 174 patients with idiopathic DO who received first-time
      100  U BoNT-A injections. The patients were collected from several previous
      clinical trials. The therapeutic effects were classified as significant sensory
      effects with urgency severity score reductions of >=2 and/or significant motor
      effects with cystometric bladder capacity increases of >=25%. The treatment
      results based on patients' perceptions of bladder conditions and long-term
      success rates were analyzed among the different therapeutic-effect subgroups.
      RESULTS: A successful outcome was reported by 138 (79.3%) patients at 3 months.
      Seventy-seven (44.3%) patients had both sensory and motor effects, 5 (2.9%) had
      sensory effects alone, 83 (47.7%) had motor effects alone, and 9 (5.2%) had no
      sensory or motor effect. All 82 patients with sensory with/without motor effects
      reported a successful result. In contrast, only 50 (60.2%) patients with motor
      effects alone reported success at 3 months. Increased cystometric bladder
      capacity and postvoid residual and decreased voiding efficiency were noted in
      patients with motor with/without sensory effects. The therapeutic results lasted
      significantly longer in patients with sensory with/without motor effects than
      those with motor effects alone. CONCLUSIONS: Improvement of urgency severity is
      significantly associated with a higher success rate at 3 months and longer
      therapeutic duration after intravesical BoNT-A injection for IDO.

PMID- 21717502
TI  - Electrical stimulation for lower urinary tract dysfunction in children: a
      systematic review of the literature.
AB  - AIMS: To review studies using electrical neural stimulation (ENS), to treat
      children with non-neurogenic lower urinary tract dysfunctions (LUTD), and to
      establish the efficacy of this treatment. METHODS: This review was based on an
      electronic search of the MEDLINE database and the Cochrane Central Search
      library, from January 1990 to March 2010. INCLUSION CRITERIA: (1) participants
      aged 0-17 years, (2) participants with a diagnosis of LUTD not related to
      congenital abnormalities or neurological disease, (3) English language, and (4)
      treatment by ENS. RESULTS: Seventeen papers were evaluated. Type of ENS varied
      among studies: sacral transcutaneous ENS in seven, sacral implanted device in
      four, posterior tibial percutaneous in three, and anogenital, endoanal, and
      intravesical in one each. There were two randomized clinical trials. Clarity
      regarding the LUTD being treated was variable. The populations studied were not
      homogeneous. The duration of treatment and the number of sessions a week were
      variable among the studies. Electrical parameters used also varied. A range of
      subjective and objective measures was used to measure treatment success. Rates of
      complete resolution of the symptoms of OAB, urgency, and daytime incontinence
      ranged from 31% to 86% [Trsinar and Kraij, Neurourol Urodyn 15: 133-42, 1996;
      Hagstroem et al., J Urol 182: 2072-8, 2009], 25% to 84% [Hoebeke et al., J Urol
      168: 2605-8, 2002; Lordelo et al., J Urol 182: 2900-4, 2009], 13% to 84% [Malm
      Buatsi et al., Urology 70: 980-3, 2007; Lordelo et al., J Urol 184: 683-9, 2010],
      respectively. For sacral transcutaneous ENS recurrence ranged from 10% to 25%.
      Apart from the sacral implantation studies, any reported side effects were mild
      and transitory. CONCLUSIONS: The literature in the area of interest is sparse.
      Parasacral TENS has been shown to be more effective than sham in randomized
      trials in treating OAB. This deserves further research to elucidate the optimal
      parameters and the children for whom it is most useful.

PMID- 21717503
TI  - Developmental and spinal cord injury-induced changes in nitric oxide-mediated
      inhibition in rat urinary bladder.
AB  - AIMS: During postnatal development large amplitude spontaneous activity of the
      neonatal rat bladder changes to a low amplitude adult pattern of activity that
      leads to improved storage function. Previously, we have shown that spontaneous
      activity in neonatal rat bladder strips is inhibited by activation of the nitric
      oxide (NO)-cGMP signaling pathway. In the present experiments we determined if
      this inhibitory pathway is altered during postnatal development or spinal cord
      injury. METHODS: Baseline tone and amplitude and frequency of spontaneous
      contractions were measured in bladder strips from male or female neonatal (days
      10-21), juvenile (days 24-39) and adult female spinal cord intact or chronic
      spinal cord injured Sprague-Dawley rats. RESULTS: The inhibitory effects of an NO
      donor (SNAP) and a PDE-5 inhibitor (zaprinast) on spontaneous activity of bladder
      strips decreased during postnatal development, while an inhibitory effect of 8
      bromo-cGMP, which was blocked by a protein kinase G inhibitor, was detected at
      all ages tested. However, the effect of NO-cGMP signaling to reduce baseline tone
      emerged during postnatal development. The inhibition induced by the NO donor was
      blocked by an inhibitor of soluble guanylyl cyclase (sGC). Chronic spinal cord
      injury (cSCI), which causes the re-emergence of a neonatal-like pattern of
      spontaneous activity, did not restore sensitivity to NO-mediated inhibition in
      adult rat bladders. CONCLUSIONS: These data indicate that while cGMP signaling
      inhibits activity in young and adult bladders as well as after cSCI, there is a
      developmental decrease in the sensitivity of bladder to NO-mediated inhibition.

PMID- 21717504
TI  - Racial differences in self-reported healthcare seeking and treatment for urinary
      incontinence in community-dwelling women from the EPI Study.
AB  - AIMS: Objectives of this study are: (1) to examine the prevalence of healthcare
      seeking among black and white women with self-reported urinary incontinence (UI),
      (2) to investigate barriers to treatment for incontinence, and (3) To investigate
      commonly used therapeutic modalities for UI. METHODS: This is a planned secondary
      analysis of responses from 2,812 black and white community-dwelling women living
      in southeastern Michigan, aged 35-64 years, who completed a telephone interview
      concerning UI, healthcare-seeking behaviors and management strategies. The study
      population was 571 subjects (278 black, 293 white) who self-identified as having
      urinary incontinence. RESULTS: Of these women with UI, 51% sought healthcare with
      no statistically significant difference between the two races (53% black, 50.6%
      white, P = 0.64). In multivariate logistic regression analysis, a higher
      likelihood of seeking healthcare was associated with increased age, body mass
      index lower than 30  kg/m(2) , prior surgery for UI, having regular pelvic exams,
      having a doctor, and worsening severity of UI. There was no significant
      association between hypothesized barriers to care seeking and race. Almost 95% of
      the subjects identified lack of knowledge of available treatments as one barrier.
      Black and white women were similar in percentage use of medications and some self
      care strategies, for example, pad wearing and bathroom mapping, but black women
      were significantly more likely to restrict fluid intake than white women and
      marginally less likely to perform Kegels. CONCLUSIONS: Black and white women seek
      healthcare for UI at similar, low rates. Improved patient-doctor relationships
      and public education may foster healthcare seeking behavior.

PMID- 21717505
TI  - Effect of repeated detrusor onabotulinumtoxinA injections on bladder and renal
      function in patients with chronic spinal cord injuries.
AB  - AIMS: To investigate the therapeutic effects of repeated detrusor
      onabotulinumtoxinA injections on urinary incontinence and renal function in
      patients with chronic spinal cord injuries (SCI). METHODS: Patients with
      suprasacral SCI were enrolled. OnabotulinumtoxinA 200  U detrusor injections were
      repeated every 6 months for four times. Patients were instructed to perform clean
      intermittent catheterization during the treatment and follow-up periods.
      Videourodynamic study and 99mTc-DTPA renal scanning for glomerular filtration
      rate (GFR) were performed at screening and every 3 months to assess the
      therapeutic effects on bladder and renal function. Quality of life was measured
      by the UDI-6, IIQ-7, and self-assessed QoL indices. Adverse events were also
      recorded. RESULTS: A total of 33 patients completed the study, 30 had improvement
      in incontinence grade (n = 18) or became completely dry (n = 12) after initial
      and subsequent onabotulinumtoxinA injections. Mean bladder capacity increased
      from 207  +/-  111 to 412  +/-  33  ml and mean detrusor pressure decreased from
      39.8  +/-  21.7 to 20.6  +/-  19.1  cmH(2) O (all P < 0.05). However, the mean
      GFR decreased from 93.4  +/-  20.4 to 83.5 +/-  24  ml/min (P = 0.028). A
      significant reduction in GFR was noted in patients with bladder compliance that
      increased by <10  cmH(2) O (P = 0.002) and in patients with Pdet decreased by <10
      cmH(2) O after treatment (P = 0.036). All 30 patients with improvement in
      incontinence grade satisfied with treatment result. CONCLUSION: This pilot study
      revealed that repeated detrusor injections of 200  U onabotulinumtoxinA could
      reduce incontinence grade, increase bladder capacity, and decrease intravesical
      pressure but this study did not demonstrate an improvement in GFR over a 24-month
      period in patients with chronic SCI.

PMID- 21717506
TI  - Evidence for autonomic nervous system dysfunction in females with idiopathic
      overactive bladder syndrome.
AB  - AIMS: Micturition and continence are largely under the control of the autonomic
      nervous system (ANS). In this study, we analyzed ANS function using autonomic
      cardiovascular (CV) testing in females with idiopathic overactive bladder
      syndrome (iOAB) versus control females. Our hypothesis was that ANS dysfunction
      could comprise part of the pathophysiology of iOAB. METHODS: Twenty-three females
      with iOAB and 29 controls were enrolled into this prospective study. Patients
      performed CV autonomic testing, including two sympathetic tests (hand grip
      exercise and cold pressor test), two parasympathetic tests (deep breathing and
      30:15 ratio), and two mixed tests (Valsalva manoeuvre and blood pressure [BP]
      response to standing). Patients with iOAB also underwent conventional urodynamic
      studies in order to define iOAB as either with or without demonstrable detrusor
      overactivity (DO). RESULTS: Both groups were similar with respect to age and
      menopausal status. Females with iOAB had significantly more positive tests than
      controls (P < 0.0001), particularly for sympathetic tests (P < 0.0001). Among the
      iOAB group, the sympathetic tests (P = 0.03) were significantly more often
      positive in patients without DO (based on cystometry) compared to patients with
      DO, with the results being particularly significant for the cold pressor test (P
      = 0.02). No differences were found among iOAB sufferers with respect to a past
      history of enuresis. CONCLUSIONS: These results suggest ANS dysfunction,
      predominantly a sympathetic ANS dysfunction, is associated with iOAB,
      specifically in patients with iOAB without DO.

PMID- 21717507
TI  - Functional characterization of a chronic cyclophosphamide-induced overactive
      bladder model in mice.
AB  - AIMS: To describe a new mouse model of overactive bladder (OAB) at the
      histological level, pain, voiding behavior, and urodynamics, while assessing the
      physiological state of mice. METHODS: This paper compares the pathophysiological
      features of mice that received intraperitoneal injections of cyclophosphamide
      (CYP) (40 and 80  mg/kg - body weight) every 2 days for 7 days. Specifically, the
      heart rate, the body temperature, and the general activity were assessed by
      telemetry. The abdominal sensitivity was determined with Von Frey filaments.
      Voiding behavior and detrusor activity were respectively quantified by urine
      spotting experiments and cystometry. Hematoxylin & Eosin staining was performed
      to detect inflammation in tissue and NGF concentration in urine was quantified.
      RESULTS: Affected mice exhibit clearly an OAB characterized by an increase in the
      number of voiding events and an urodynamically-demonstrated detrusor overactivity
      associated with referred hyperalgesia. The injected mice displayed inflamed
      bladder, urothelial hyperplasia, and increased NGF concentration in urine in dose
      dependant manner. However, the physiological features of mice with CYP-induced
      cystitis are not changed. CONCLUSIONS: We can show that this model of chronic OAB
      with pain in mice fits more closely to the clinical signs of patients with OAB
      than the available animal models (acute and chronic) and will therefore be useful
      to highlight potential drug targets in genetically modified mice in the future.

PMID- 21717508
TI  - Cortical gray matter changes in primary blepharospasm: a voxel-based morphometry
      study.
AB  - Previous voxel-based morphometry studies of patients with primary blepharospasm
      documented gray matter volumetric differences of the striatum, cerebellum,
      thalamus, and parietal lobe areas. However, these results were inconsistent
      across studies, which recruited relatively small samples and did not always
      provide detailed clinical information on patients with blepharospasm. The
      objective of this study was to analyze whole-brain gray matter volume in a larger
      sample of patients with blepharospasm and to expand on previous works by
      evaluating whether clinical features of blepharospasm correlate to whole-brain
      gray matter changes. Voxel-based morphometry was performed on 25 patients with
      primary adult-onset blepharospasm and 24 healthy subjects (controls) matched for
      age, sex, and handedness. Clinical data were collected through a standardized
      interview. Severity of blepharospasm was measured using the Jankovic Rating
      Scale. Patients with blepharospasm had greater gray matter volume than controls
      in the right middle frontal gyrus, whereas patients with blepharospasm had
      smaller gray matter volume than controls in the left postcentral gyrus and left
      superior temporal gyrus. Spearman correlation analysis with Bonferroni correction
      failed to show significant correlations between gray matter volume and the
      explored clinical variables, comprising age at onset, disease duration,
      blepharospasm severity, presence of an effective geste antagoniste, and dose and
      duration of botulinum toxin treatment. Patients with blepharospasm exhibited gray
      matter volume differences exclusively in cortical regions highly relevant to
      sensory processing and cognitive modulation of motor behavior. Gray matter
      changes in the primary sensory cortex may represent a common trait of primary
      dystonias, including blepharospasm.

PMID- 21717509
TI  - Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene.
AB  - OBJECTIVE: Single nucleotide polymorphisms (SNPs) in serotonin related genes
      influence mental disorders, responses to pharmacological and psychotherapeutic
      treatments. In planning association studies, researchers that want to investigate
      new SNPs have to select some among a large number of candidates. Our aim is to
      guide researchers in the selection of the most likely phenotype affecting
      polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till
      now, only relatively few of about 2000 are investigated. METHODS: We used the
      most updated and assessed bioinformatic tools to predict which variations can
      give rise to biological effects among 2450 HTR2C SNPs. RESULTS: We suggest 48
      SNPs that are worth considering in future association studies in the field of
      psychiatry, psychology and pharmacogenomics. Moreover, our analyses point out the
      biological level probably affected, such as transcription, splicing, miRNA
      regulation and protein structure, thus allowing to suggest future molecular
      investigations. CONCLUSIONS: Although few association studies are available in
      literature, their results are in agreement with our predictions, showing that our
      selection methods can help to guide future association studies.

PMID- 21717510
TI  - The reactivity of a silacyclopentadienylidene towards aldehydes: silole ring
      expansion and the formation of base-stabilized silacyclohexadienones.
AB  - Tossing aldehydes into the ring: The reaction of a silacyclopentadienylidene with
      aldehydes leads to C=O bond cleavage with the formation of base-stabilized
      silanones and cyclopropanation of the adjacent C=C bond, followed by silole ring
      expansion to give silicon analogues of cyclohexadienones.

PMID- 21717511
TI  - Meaningful structural descriptors from charge density.
AB  - This paper provides a short introduction to the basics of electron density
      investigations. The two predominant approaches for the modelling and various
      interpretations of electron density distributions are presented. Their potential
      translations into chemical concepts are explained. The focus of the article lies
      on the deduction of chemical properties from charge density studies in some
      selected main group compounds. The relationship between the obtained numerical
      data and commonly accepted simple chemical concepts unfortunately is not always
      straightforward, and often the chemist relies on heuristic connections rather
      than rigorously defined ones. This article tries to demonstrate how charge
      density analyses can shed light on aspects of chemical bonding and reactivity
      resulting from the determined bonding situation. Sometimes this helps to identify
      misconceptions and sets the scene for new unconventional synthetic approaches.

PMID- 21717512
TI  - Energy up-conversion by low-power excitation: new applications of an old concept.
AB  - Energy up-conversion is the process by which two absorbed photons are converted
      in one photon of higher energy. Such a process can be conveniently performed by
      low-power excitation through sensitized triplet-triplet annihilation and it is
      now an emerging technique with possible applications in different fields,
      including photovoltaic devices and bioimaging.

PMID- 21717513
TI  - Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the
      activity of NF-kappaB and MAP kinases in lipopolysaccharide-treated PC12 cells.
AB  - As an active compound extracted from the Chinese herb Tripterygium wilfordii,
      triptolide (TP) was demonstrated to have potent antiinflammatory and
      immunosuppressive properties in previous studies. Recently, it has been shown
      that TP prevented the loss of dopaminergic neurons in the substantia nigra of
      rats in a model of Parkinson's disease, but little is known about the precise
      neuroprotective mechanism of TP. This study was designed to elucidate whether the
      neuroprotective effect of TP is partially based on its direct inhibition of
      inflammatory molecules by investigating the effects of TP on the expression of
      cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) related to the nuclear factor
      (NF)-kappaB pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. The
      activation of related upstream molecules such as NF-kappaB, P38, extracellular
      signal-regulated kinase (ERK)1/2, and beta-alanyl-alpha-ketoglutarate
      transaminase (AKT), in PC12 cells were investigated by real time polymerase chain
      reaction (PCR), western blotting and enzyme-linked immunosorbent assay (ELISA).
      Our results showed that TP directly inhibited the expression of both mRNA and
      protein of COX-2 (p < 0.01), decreased PGE2 production (p < 0.01) in a dose
      dependent manner, down-regulated NF-kappaB activity (p < 0.01), and significantly
      inhibited the phosphorylation of p38, ERK1/2 (p42/p44) and AKT in PC12 cells
      after LPS challenge. This suggests that the neuroprotective effects of TP may be
      partially mediated by direct inhibition of the expression of COX-2, activation of
      NF-kappaB, and phosphorylation of p38, ERK1/2 (p42/p44) and AKT proteins of
      neuronal cells.

PMID- 21717514
TI  - Effects of armepavine against hepatic fibrosis induced by thioacetamide in rats.
AB  - The aim of this study was to investigate if armepavine (Arm, C19H23O3N) could
      exert inhibitory effects against hepatic fibrosis in rats. A cell line of rat
      hepatic stellate cells (HSC-T6) was stimulated with tumour necrosis factor-alpha
      (TNF-alpha) to evaluate the inhibitory effects of Arm. Rats were injected with
      thioacetamide (TAA; 300 mg/kg, intraperitoneally) thrice a week for 4 weeks to
      induce hepatic fibrosis, with Arm (3 or 10 mg/kg) given by gavage twice a day.
      Liver sections were taken for western blotting, fibrosis scoring and
      immunofluorescence staining. Arm (1-10 um) concentration-dependently attenuated
      TNF-alpha-stimulated: (i) protein expressions of alpha-smooth muscle actin (alpha
      SMA), collagen type I and angiopoietin-1; (ii) H2O2 production; and (iii) NF
      kappaB, JunD and C/EBPbeta (cytidine-cytidine-adenosine-adenosine-thymidine
      (CCAAT)/enhancer binding protein-beta (EBPbeta)) nuclear translocations in HSC-T6
      cells. In vivo Arm treatment significantly reduced plasma aspartate transaminase
      and alanine transaminase levels, hepatic alpha-SMA expression and collagen
      contents, and fibrosis scores of TAA-injected rats. Moreover, Arm treatment
      decreased alpha-SMA- and NF-kappaB-positive cells in immunohistochemical
      staining, and mRNA expression levels of IL-6, TGF-beta1, TIMP-1, col1alpha2, iNOS
      and ICAM-1 genes, but up-regulated the metallothionein gene in the livers of TAA
      injected rats. Our results indicated that Arm exerted both in vitro and in vivo
      antifibrotic effects in rats, with inhibition of NF-kappaB, JunD and C/EBPbeta
      pathways.

PMID- 21717515
TI  - The effects of an Echinacea preparation on synaptic transmission and the firing
      properties of CA1 pyramidal cells in the hippocampus.
AB  - Traditionally, Echinacea preparations are used as antiinflammatory agents and
      immune-enhancers. In addition to these effects, their anxiolytic potency has been
      recognized recently in laboratory tests. Our aim in this study was to uncover the
      potential effects of an Echinacea preparation on neuronal operations in the
      hippocampus, a brain region that is involved in anxiety and anxiety-related
      behaviors. Using in vitro electrophysiological techniques, we observed that
      excitatory synaptic transmission in hippocampal slices was significantly
      suppressed by an Echinacea extract found to be effective in anxiety tests. In
      contrast, no change in inhibitory synaptic transmission could be detected upon
      application of this extract. In addition, our experiments revealed that at low
      concentration the Echinacea extract reduced the spiking activity of CA1 pyramidal
      cells, while at high concentration increased it. This latter observation was
      parallel to the reduction in the magnitude of the h-current-mediated voltage
      responses in pyramidal cells. At any concentrations, the passive membrane
      properties of CA1 pyramidal cells were found to be unaltered by the Echinacea
      extract. In summary, the Echinacea extract can significantly regulate excitatory,
      but not inhibitory, synaptic transmission in the hippocampus, and this action
      might be involved in its anxiolytic effects observed in behaviour tests.

PMID- 21717516
TI  - Effects of 12-week oral supplementation of Ecklonia cava polyphenols on
      anthropometric and blood lipid parameters in overweight Korean individuals: a
      double-blind randomized clinical trial.
AB  - The effects of 12-week supplementation with a polyphenol extract from Ecklonia
      cava (ECP) on anthropometry, serum biochemistry and hematology have been
      investigated. Ninety-seven overweight male and female adults (average age 40.5 +/
      9.2 yr and body mass index (BMI) of 26.5 +/- 1.6 kg/m2) were enrolled in a
      randomized, double-blind, placebo-controlled trial with parallel-group design.
      Subjects were randomly allocated into three groups designated as PC (placebo), LD
      (low-dose, 72 mg-ECP/day) and HD (high-dose, 144 mg-ECP/day). Both LD and HD
      groups showed significant decreases in BMI, body fat ratio, waist circumference,
      waist/hip ratio, total cholesterol, low-density lipoprotein (LDL) cholesterol,
      total cholesterol/high-density lipoprotein (HDL) cholesterol and atherogenic
      index (AI) after 12 weeks, as compared with the placebo group. The HD group also
      showed a significant increase in serum HDL cholesterol as compared with the
      placebo group. Only the HD group showed significant decreases in serum glucose
      and systolic blood pressure after 12 weeks. There was no significant adverse
      event related with ingestion of ECP, and serum biochemical and hematological
      parameters were maintained within normal range during the intervention period. In
      conclusion, these results demonstrated that ECP supplementation significantly
      contributed to lowering body fat and serum lipid parameters such as total and LDL
      cholesterols with dose dependence. Further studies using different populations,
      dosages or biological markers are highly recommended to better understand the
      physiological features of this polyphenol.

PMID- 21717517
TI  - Chronic intraperitoneal and oral treatments with hesperidin induce central
      nervous system effects in mice.
AB  - Hesperidin (HN) is a flavanone glycoside abundantly found in citrus fruits. This
      flavonoid mediated central nervous system activity following intraperitoneal
      (i.p.) acute treatment. The responses of mice after the chronic i.p. (4 and 30
      mg/kg/day) or the oral intake administration of this drug (20, 50 and 100
      mg/kg/day) were studied by using the holeboard, the plus-maze and the locomotor
      activity tests. Hesperidin, chronically administered by the i.p. route, exerted a
      decrease in the locomotor and exploratory activities, thus evidencing a
      depressant activity. In turn, the chronic oral intake of this flavonoid induced
      anxiolytic-like effects. These varied responses could be attributed to the
      different routes of administration that could lead to the production of diverse
      active metabolites.

PMID- 21717518
TI  - Topical application of two condensed tannins from the root of Rosa multiflora
      Thunberg for the treatment of atopic dermatitis (AD) in NC/Nga mice.
AB  - Recently, the isolation of several condensed tannins from the roots of Rosa
      multiflora Thunberg, a traditional herbal therapy in oriental medicine for
      rheumatoid arthritis and scabies, was described. Two of the major condensed
      tannins - procyanidin B-3 (ProB3) and ent-guibourtinidol-(4beta -> 6)-catechin
      (RM-1) - were then applied topically to atopic dermatitis-like skin lesions on
      NC/Nga mice in order to assess their immunomodulatory properties. Both ProB3 and
      RM-1 significantly reduced the serum levels of eosinophils, IgE and certain Th2
      cytokines (IL-4, 5 and 13) (p < 0.05 or 0.01). Additionally, ProB3 and RM-1
      significantly reduced both the mRNA and protein expression of COX-2 and iNOS in
      mouse skin tissues (p < 0.01). Such results strongly suggest that ProB3 and RM-1
      may be useful in the treatment allergic skin conditions, most notably atopic
      dermatitis.

PMID- 21717519
TI  - Parafibromin immunohistochemical staining to differentiate parathyroid carcinoma
      from parathyroid adenoma.
AB  - BACKGROUND: Parafibromin is a protein encoded by the HRPT2 oncosuppressor gene,
      and the expression is reported to be decreased or absent in parathyroid
      carcinomas. METHODS: A total of 26 tumor specimens from 18 patients with adenoma
      and 8 patients with carcinoma were immune-stained with an antibody against
      parafibromin. RESULTS: Parafibromin immunostaining showed strong positivity in 17
      of 18 adenomas. Negative staining was noted in 3 of 8 carcinomas, and weak
      positivity was found in 3 of 8 carcinomas. The remaining 2 cases of carcinoma
      showed strong positivity. The loss of parafibromin expression (negative or weak
      positivity) demonstrated 94.4% specificity in the diagnosis of parathyroid
      carcinomas. Relapses or distant metastases of carcinoma occurred only in cases in
      which there was a loss of parafibromin immunostaining. CONCLUSIONS: Loss of
      parafibromin immunostating showed promising results in the differential diagnosis
      of parathyroid carcinoma from adenoma and may also serve as a prognostic marker.

PMID- 21717520
TI  - Interleukin-23 receptor polymorphism as a risk factor for oral cancer
      susceptibility.
AB  - BACKGROUND: The purpose of this study was to evaluate the influence of genetic
      polymorphisms of interleukin (IL)-23 and the IL-23 receptor (IL-23R) on the
      susceptibility to oral cancer. METHODS: Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) was used to measure polymorphisms of
      these genes in 240 controls and 240 patients with oral cancer. RESULTS:
      Individuals with at least 1 varied C allele of rs10889677 (IL-23R polymorphism)
      had a 1.553-fold risk (95% confidence interval [CI], 1.073-2.241) of developing
      oral cancer compared with patients with the wild-type A/A homozygote. Patients
      with oral cancer with at least 1 varied C allele of rs10889677 had a 1.931-fold
      risk of tumor lymph node metastasis compared with patients with the C/C
      homozygote. CONCLUSION: The varied C allele of the IL-23R gene may be considered
      a factor contributing to increased susceptibility and may be a predictive factor
      for tumor lymph node metastasis in Taiwanese with oral cancer.

PMID- 21717521
TI  - Chondrolipoma of head and neck: case report and review of literature.
AB  - BACKGROUND: Chondrolipoma is a rare form of a benign mesenchymal tumor containing
      mature cartilage and fatty tissue. Chondrolipomas may be found in almost any part
      of the body, particularly in the connective tissue of the breast, head and neck
      area, and in the skeletal muscle. METHODS: We present the case of a 51-year-old
      woman complaining of 8 to 9 months of intermittent right cheek swelling. Magnetic
      resonance imaging (MRI) and CT scans showed a 4.0-cm fat-containing mass
      involving the right masseter muscle. RESULTS: The patient was taken to the
      operating room for excision of the mass. The final pathologic diagnosis was
      chondrolipoma. CONCLUSIONS: We describe a case of a chondrolipoma in the masseter
      muscle.

PMID- 21717522
TI  - Chondrocytes suspended in modified fibrin glue for vocal fold augmentation: An in
      vitro study in a porcine larynx model.
AB  - BACKGROUND: Injection laryngoplasty is an option for treatment of dysphonia
      following vocal fold paralysis. Modified fibrin glue with suspended chondrocytes
      might be a favorable cell-based material for permanent vocal fold medialization.
      METHODS: We compared fibrin glue with suspended chondrocytes to collagen and
      hyaluronic acid gels concerning alteration of vocal fold vibration and correct
      intralaryngeal placement after intralaryngeal injection into porcine larynges.
      Viscoelastic properties of the materials were analyzed by means of a parallel
      plate rheometer. RESULTS: Fibrin glue with cells was comparable to collagen and
      hyaluronic acid with respect to amplitudes, symmetry, and periodicity of vocal
      fold vibration. Application and positioning of fibrin glue with suspended
      chondrocytes were technically undemanding and comparable with controls. Complex
      stress modulus of fibrin glue with suspended cells was comparable to that of
      collagen gel. CONCLUSIONS: Fibrin glue with suspended chondrocytes seems suitable
      for the indication of injection laryngoplasty and holds promise for permanent
      vocal fold medialization.

PMID- 21717523
TI  - Trends in the incidence of oral cavity and oropharyngeal cancers in Spain.
AB  - BACKGROUND: The purpose of this study was to analyze and compare incidence trends
      of oral cavity and oropharyngeal cancers, using data from population-based
      Spanish cancer registries. METHODS: Adjusted rates were calculated using the
      standard world population, and incidence trends were analyzed for individual and
      pooled registries using joinpoint regression. RESULTS: Analysis of 7 pooled
      registries revealed a statistically significant reduction in the incidence of
      oral cavity cancer in men (annual percent change [APC] = -3.1) and a
      nonsignificant decrease in women (APC = -4.5) over the period from 1991 to 2001.
      For oropharyngeal cancer, the trend was for a statistically significant increase
      in men in 4 registries. CONCLUSION: There is growing evidence that the incidence
      of oral cavity cancer is in decline, while the incidence of oropharyngeal cancer
      has been increasing over the past 3 decades, especially in developed countries,
      and this study reinforces such evidence.

PMID- 21717524
TI  - Prognostic significance of RB1-inducible coiled-coil 1 in salivary gland cancers.
AB  - 7 BACKGROUND: No generally agreed-upon method is available for predicting the
      prognosis of salivary gland cancers. RB1-inducible coiled-coil 1 (RB1CC1) is a
      positive regulator for the retinoblastoma tumor suppressor (RB1) pathway, and is
      a suitable marker for evaluating the clinical course of breast cancer. We
      investigated whether RB1CC1 predicts the prognosis of salivary gland cancers.
      METHODS: Molecules involved in the RB1CC1 pathway, including RB1CC1, RB1, p53,
      and Ki-67, were evaluated immunohistochemically in 36 cases of salivary gland
      cancers. The relationships between clinicopathologic features and disease-free
      survival intervals were analyzed by a Kaplan-Meier log-rank test and a
      multivariate Cox proportional hazard regression. RESULTS: Nuclear RB1CC1 loss in
      the tumors was significantly associated with a worse disease-free survival (log
      rank test, chi-square value = 11.644, p = .0006), and was the maximum critical
      risk (multivariate Cox proportional hazard ratio = 11.112, 95% confidence
      interval [CI] = 1.776-69.510, p = .0100). CONCLUSIONS: Nuclear expression of
      RB1CC1 predicts a better clinical outcome and is useful in the follow-up of
      salivary gland cancers.

PMID- 21717525
TI  - Oncocytic carcinoma of the nasolacrimal duct treated by transnasal endoscopic
      resection.
AB  - BACKGROUND: Malignancies of the nasolacrimal apparatus are rare lesions that
      usually originate from the lacrimal sac. To the best of our knowledge, this is
      the first case of a primary oncocytic carcinoma of the nasolacrimal duct reported
      in the literature. METHODS: A 43-year-old woman presented with a 3-month history
      of right epiphora. At nasal endoscopy, an exophytic lesion occupying the right
      inferior meatus was visible. Imaging studies showed an expansile lesion involving
      the nasolacrimal duct and the inferior meatus, but not invading the orbit or
      adjacent soft tissues. A biopsy was suggestive for an oncocytic lesion. RESULTS:
      A radical resection was obtained through an endoscopic extended medial
      maxillectomy with a definitive diagnosis of oncocytic carcinoma. Forty-two months
      after surgery there was no evidence of disease. CONCLUSIONS: In selected
      malignant lesions of the nasolacrimal duct not involving the adjacent soft
      tissues or lacrimal sac, an exclusive endoscopic approach can be considered.

PMID- 21717526
TI  - Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both
      myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor.
AB  - Despite their shared predilection for superficial soft tissue of distal
      extremities and frequent local recurrences, myxoinflammatory fibroblastic sarcoma
      (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT) have distinct morphologic
      appearances. Recent studies have identified an identical t(1;10)(p22;q24) in five
      cases of MIFS and two of HFLT, as well as common amplifications on 3p11-12. To
      investigate further their potential relationship and to determine the incidence
      of t(1;10) in a larger cohort, we subjected seven MIFS, 14 HFLT, and three cases
      with mixed morphology, to molecular and cytogenetic analysis. Fluorescence in
      situ hybridization (FISH) analysis for rearrangements of TGFBR3 on 1p22 and of
      MGEA5 on 10q24 was performed in all cases, whereas the status of VGLL3 gene
      amplification on 3p12.1 was investigated in 12 cases. Conventional karyotyping
      was performed in one HFLT and two cases with mixed MIFS/HFLT histology. Overall
      83% of cases showed rearrangements in both TGFBR3 and MGEA5. All three cases with
      mixed features of MIFS and HFLT were positive. Cytogenetic analysis performed in
      three cases confirmed an unbalanced der(10)t(1;10)(p22;q24). VGLL3 gene
      amplification was noted in 10/12 cases of both histologies. The high incidence of
      t(1;10) in MIFS and HFLT reinforces a shared pathogenetic relationship.
      Furthermore, the co-existence of both components either synchronously or
      metachronously in a primary or subsequent recurrence, suggest either different
      morphologic variants or different levels of tumor progression of a single
      biologic entity. FISH analysis for TGFBR3 and MGEA5 rearrangements can be applied
      as a reliable diagnostic molecular test when confronted with limited material or
      a challenging diagnosis.

PMID- 21717527
TI  - Genomic aberrations in pediatric gliomas and embryonal tumors.
AB  - The pathogenesis of pediatric central nervous system tumors is poorly understood.
      To increase knowledge about the genetic mechanisms underlying these tumors, we
      performed genome-wide screening of 17 pediatric gliomas and embryonal tumors
      combining G-band karyotyping and array comparative genomic hybridization (aCGH).
      G-banding revealed abnormal karyotypes in 56% of tumor samples (9 of 16; one
      failed in culture), whereas aCGH found copy number aberrations in all 13 tumors
      examined. Pilocytic astrocytomas (n = 3) showed normal karyotypes or nonrecurrent
      translocations by karyotyping but the well-established recurrent gain of 7q34 and
      19p13.3 by aCGH. Our series included one anaplastic oligoastrocytoma, a tumor
      type not previously characterized genomically in children, and one anaplastic
      neuroepithelial tumor (probably an oligoastrocytoma); both showed loss of
      chromosome 14 by G-banding and structural aberrations of 6q and loss of 14q, 17p,
      and 22q by aCGH. Three of five supratentorial primitive neuroectodermal tumors
      showed aberrant karyotypes: two were near-diploid with mainly structural changes
      and one was near-triploid with several trisomies. aCGH confirmed these findings
      and revealed additional recurrent gains of 1q21-44 and losses of 3p21, 3q26, and
      8p23. We describe cytogenetically for the first time a cribriform neuroepithelial
      tumor, a recently identified variant of atypical teratoid/rhabdoid tumor with a
      favorable prognosis, which showed loss of 1p33, 4q13.2, 10p12.31, 10q11.22, and
      22q by aCGH. This study indicates the existence of distinct cytogenetic patterns
      in pediatric gliomas and embryonal tumors; however, further studies of these rare
      tumors using a multimodal approach are required before their true genomic
      aberration pattern can be finally established.

PMID- 21717528
TI  - Confounding adjustment via a semi-automated high-dimensional propensity score
      algorithm: an application to electronic medical records.
AB  - PURPOSE: A semi-automated high-dimensional propensity score (hd-PS) algorithm has
      been proposed to adjust for confounding in claims databases. The feasibility of
      using this algorithm in other types of healthcare databases is unknown. METHODS:
      We estimated the comparative safety of traditional non-steroidal anti
      inflammatory drugs (NSAIDs) and selective COX-2 inhibitors regarding the risk of
      upper gastrointestinal bleeding (UGIB) in The Health Improvement Network, an
      electronic medical record (EMR) database in the UK. We compared the adjusted
      effect estimates when the confounders were identified using expert knowledge or
      the semi-automated hd-PS algorithm. RESULTS: Compared with the 411,616
      traditional NSAID initiators, the crude odds ratio (OR) of UGIB was 1.50 (95%CI:
      0.98, 2.28) for the 43,569 selective COX-2 inhibitor initiators. The OR dropped
      to 0.81 (0.52, 1.27) upon adjustment for known risk factors for UGIB that are
      typically available in both claims and EMR databases. The OR remained similar
      when further adjusting for covariates--smoking, alcohol consumption, and body
      mass index-that are not typically recorded in claims databases (OR 0.81; 0.51,
      1.26) or adding 500 empirically identified covariates using the hd-PS algorithm
      (OR 0.78; 0.49, 1.22). Adjusting for age and sex plus 500 empirically identified
      covariates produced an OR of 0.87 (0.56, 1.34). CONCLUSIONS: The hd-PS algorithm
      can be implemented in pharmacoepidemiologic studies that use primary care EMR
      databases such as The Health Improvement Network. For the NSAID-UGIB association
      for which major confounders are well known, further adjustment for covariates
      selected by the algorithm had little impact on the effect estimate.

PMID- 21717529
TI  - Acetaminophen overdose: a little recognized public health threat.

PMID- 21717530
TI  - [Au(CF3)(CO)]: a gold carbonyl compound stabilized by a trifluoromethyl group.

PMID- 21717531
TI  - Magical power of transition metals: past, present, and future (Nobel Lecture).

PMID- 21717532
TI  - Synthesis of nanostructured reduced titanium oxide: crystal structure
      transformation maintaining nanomorphology.

PMID- 21717533
TI  - Theory of the kinetics of chemical potentials in heterogeneous catalysis.

PMID- 21717534
TI  - Two-dimensional molecular porous networks formed by trimesic acid and 4,4'-bis(4
      pyridyl)biphenyl on Au(111) through hierarchical hydrogen bonds: structural
      systematics and control of nanopore size and shape.

PMID- 21717535
TI  - Constitutional, configurational, and conformational analysis of small organic
      molecules on the basis of NMR residual dipolar couplings.

PMID- 21717536
TI  - Halogen-bond-induced activation of a carbon-heteroatom bond.

PMID- 21717537
TI  - Template-induced screw motions within an aromatic amide foldamer double helix.

PMID- 21717538
TI  - Gold nanoparticles presenting hybridized self-assembled aptamers that exhibit
      enhanced inhibition of thrombin.

PMID- 21717539
TI  - Double C-H bond activation of C(sp3)H2 groups for the preparation of complexes
      with back-to-back bisimidazolinylidenes.

PMID- 21717540
TI  - In-stem-labeled molecular beacons for distinct fluorescent color readout.

PMID- 21717541
TI  - Tetrahedral Mo4 clusters as building blocks for the design of clathrate-related
      giant frameworks.

PMID- 21717542
TI  - C-H bond activation of methanol and ethanol by a high-spin Fe(IV)O biomimetic
      complex.

PMID- 21717543
TI  - High-density, multiplexed patterning of cells at single-cell resolution for
      tissue engineering and other applications.

PMID- 21717544
TI  - Reactivity of a scandium terminal imido complex towards unsaturated substrates.

PMID- 21717545
TI  - A nanosized molybdenum oxide wheel with a unique electronic-necklace structure:
      STM study with submolecular resolution.

PMID- 21717546
TI  - Theory-guided experiments on the mechanistic elucidation of the reduction of
      dinuclear zinc, manganese, and cadmium complexes.

PMID- 21717547
TI  - Molecular lanthanoid-transition-metal cluster through C-H bond activation by
      polar metal-metal bonds.

PMID- 21717548
TI  - Isoxazole functionalization technologies enable construction of tetracycline
      derivatives.

PMID- 21717549
TI  - Electronic properties and reactivity of an isolable phosphagermaheterocyclic
      carbene.

PMID- 21717550
TI  - A light-stimulated molecular switch driven by radical-radical interactions in
      water.

PMID- 21717551
TI  - Dye-sensitized solar cells based on donor-acceptor pi-conjugated fluorescent dyes
      with a pyridine ring as an electron-withdrawing anchoring group.

PMID- 21717552
TI  - Synthesis and structural characterization of crystalline nonacenes.

PMID- 21717553
TI  - Recovery of a parentlike state in Ba(1-x)K(x)Fe(1.86)Co(0.14)As2.

PMID- 21717555
TI  - Sequence-regulated radical polymerization with a metal-templated monomer:
      repetitive ABA sequence by double cyclopolymerization.

PMID- 21717556
TI  - Synthesis of oximidine II by a copper-mediated reductive ene-yne
      macrocyclization.

PMID- 21717558
TI  - Chemistry's role in regenerative energy.

PMID- 21717557
TI  - Two-electron redox chemistry and reversible umpolung of a gold-antimony bond.

PMID- 21717563
TI  - Electronic properties of interfaces between PCPDTBT and prototypical electrodes
      studied by photoemission spectroscopy.
AB  - We report on the electronic structure of poly[2,6-(4,4-bis- (2-ethylhexyl)-4H
      cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT),
      a promising low-band-gap donor material for efficient bulk heterojunction organic
      solar cells. Electronic properties of interfaces formed between PCPDTBT and
      prototypical electrodes [Au, indium-tin-oxide and poly(ethylene-dioxythiophene):
      poly(styrenesulfonate)], obtained from X-ray photoemission spectroscopy and
      ultraviolet photoemission spectroscopy, are evaluated. The formation of interface
      dipoles is observed, and their consequences for device performance are discussed.
      For the system PCPDTBT/Au chemical interactions occur, which may affect in
      particular the charge extraction at the corresponding interface.

PMID- 21717564
TI  - Compressibility of gas hydrates.
AB  - Experimental data on the pressure dependence of unit cell parameters for the gas
      hydrates of ethane (cubic structure I, pressure range 0-2 GPa), xenon (cubic
      structure I, pressure range 0-1.5 GPa) and the double hydrate of
      tetrahydrofuran+xenon (cubic structure II, pressure range 0-3 GPa) are presented.
      Approximation of the data using the cubic Birch-Murnaghan equation,
      P=1.5B(0)[(V(0)/V)(7/3)-(V(0)/V)(5/3)], gave the following results: for ethane
      hydrate V(0)=1781 A(3) , B(0)=11.2 GPa; for xenon hydrate V(0)=1726 A(3) ,
      B(0)=9.3 GPa; for the double hydrate of tetrahydrofuran+xenon V(0)=5323 A(3) ,
      B(0)=8.8 GPa. In the last case, the approximation was performed within the
      pressure range 0-1.5 GPa; it is impossible to describe the results within a
      broader pressure range using the cubic Birch-Murnaghan equation. At the maximum
      pressure of the existence of the double hydrate of tetrahydrofuran+xenon (3.1
      GPa), the unit cell volume was 86% of the unit cell volume at zero pressure.
      Analysis of the experimental data obtained by us and data available from the
      literature showed that 1) the bulk modulus of gas hydrates with classical
      polyhedral structures, in most cases, are close to each other and 2) the bulk
      modulus is mainly determined by the elasticity of the hydrogen-bonded water
      framework. Variable filling of the cavities with guest molecules also has a
      substantial effect on the bulk modulus. On the basis of the obtained results, we
      concluded that the bulk modulus of gas hydrates with classical polyhedral
      structures and existing at pressures up to 1.5 GPa was equal to (9+/-2) GPa. In
      cases when data on the equations of state for the hydrates were unavailable, the
      indicated values may be recommended as the most probable ones.

PMID- 21717565
TI  - Quinclorac resistance: a concerted hormonal and enzymatic effort in Echinochloa
      phyllopogon.
AB  - BACKGROUND: Quinclorac (3,7-dichloro-quinoline-carboxylic acid) is a selective
      herbicide widely used to control annual grasses and certain broadleaf weeds.
      Echinochloa phyllopogon (Stapf) Koss. is the most noxious grass weed in
      California rice fields and has evolved resistance to multiple herbicides with
      different modes of action. A quinclorac-resistant (R) E. phyllopogon biotype
      found in a Sacramento Valley rice field where quinclorac has never been applied
      was investigated. RESULTS: Resistant to susceptible (S) GR(50) (herbicide rate
      for 50% growth reduction) ratios ranged from 6 to 17. The cytochrome P450
      inhibitor malathion (200 mg L(-1)) caused R plants to become as quinclorac
      susceptible as S plants. Quinclorac rapidly (6 HAT) stimulated ethylene formation
      in S plants, but only marginally in R plants. Malathion pretreatment did not
      reduce ethylene formation by quinclorac-treated S and R plants. Activity of beta
      cyanoalanine synthase (beta-CAS) in tissue extracts was 2-3-fold greater in R
      than in S plants, and incubation of shoot extracts with 1 mM malathion reduced
      beta-CAS activity by 40% in both biotypes. CONCLUSION: Resistance to quinclorac
      in R E. phyllopogon involved at least two mechanisms: (a) insensitivity along the
      response pathway whereby quinclorac induces ethylene production; (b) enhanced
      beta-CAS activity, which should enable greater HCN detoxification following
      quinclorac stimulation of ethylene biosynthesis. This unveils new resistance
      mechanisms for this multiple-resistant biotype widely spread throughout
      California rice fields.

PMID- 21717566
TI  - Tolerance of two Bifora radians Bieb populations to ALS inhibitors in winter
      wheat.
AB  - BACKGROUND: Bifora radians, an annual weed in winter wheat, is distributed mainly
      in the Mediterranean area, Asia Minor and the Caucasus. It infests winter-sown
      crops of the Central Anatolia and Middle Black Sea regions of Turkey. Field
      experiments in heavily B. radians-infested fields were conducted over 3 years in
      Samsun, Turkey, to determine the response of B. radians to ALS-inhibiting
      herbicides, because growers had complained of a decrease in herbicide effect.
      RESULTS: The efficacy of ALS inhibitors on a putatively tolerant population
      sprayed annually with ALS inhibitors and an adjacent allegedly sensitive
      population was estimated at the ED(50) and ED(90) response levels. The
      recommended rates of herbicides controlled 90% of the weed (ED(90)) in the
      sensitive population at the early stage of B. radians development, but not in the
      tolerant population. The relative potencies (ED(x(tolerant))/ED(x(sensitive))) of
      herbicides on the two populations were estimated by assuming years as being
      random effects. The relative potency was on average about 1.7, irrespective of
      the ED(x) levels. CONCLUSION: Although the relative potencies were not large,
      they were large enough to be noted by growers. In field experiments it would be
      important to establish tools demonstrating when farmers recognise loss of
      herbicide efficacy. There has been no indication of evolution of resistant
      biotypes so far, but continuous spraying favours biotypes with increased levels
      of tolerance.

PMID- 21717567
TI  - Triterpene saponins of Quillaja saponaria show strong aphicidal and deterrent
      activity against the pea aphid Acyrthosiphon pisum.
AB  - BACKGROUND: Saponins are a class of secondary plant metabolites consisting of a
      sugar moiety glycosidically linked to a hydrophobic aglycone (sapogenin) that
      often possess insecticidal activities. Four saponins were selected: two
      triterpene saponins, Q. saponaria saponins and aescin, and two steroidal
      saponins, digitonin and diosgenin. Their effects were investigated on an
      important pest species and a model piercing-sucking insect, the pea aphid
      Acyrthosiphon pisum. The triterpene Q. saponaria saponins bark saponin received
      special attention because of its high activity. Aphids were challenged by oral
      and contact exposure to demonstrate aphicidal activities, and in choice
      experiments to support use as a natural deterrent. RESULTS: When aphids were
      exposed to supplemented artificial diet for 3 days, a strong aphicidal activity
      was recorded for three of the four saponins, with an LC50 of 0.55 mg mL(-1) for
      Q. saponaria saponins, 0.62 mg mL(-1) for aescin and 0.45 mg mL(-1) for
      digitonin. The LT50 values ranged between 1 and 4 days, depending on the dose.
      For diosgenin, only low toxicity (14%) was scored for concentrations up to 5 mg
      mL(-1). In choice experiments with treated diet, a deterrence index of 0.97 was
      scored for Q. saponaria saponins at 1 mg mL(-1). In contrast, direct contact
      showed no repellent effect. Spraying of faba bean plants with Q. saponaria
      saponins resulted in an LC50 of 8.2 mg mL(-1). Finally, histological analysis in
      aphids fed with Q. saponaria saponins demonstrated strong aberrations of the
      aphid gut epithelium, and exposure of midgut CF-203 cell lines to Q. saponaria
      saponins in vitro confirmed the cytotoxic effect. CONCLUSIONS: The present insect
      experiments provide strong evidence that saponins, as tested here with triterpene
      Q. saponaria saponins, can be useful as natural aphicides and deterrents.
      Furthermore, the insect midgut epithelium is suggested to be a primary target of
      saponin activity.

PMID- 21717571
TI  - Creating a human brain proteome atlas--13th HUPO BPP Workshop March 30-31, 2010,
      Ochang, Korea.
AB  - The HUPO Brain Proteome Project (HUPO BPP) held its 13th workshop in Ochang from
      March 30th to 31st, 2010 prior to the Korean HUPO 10th Annual International
      Proteomics Conference. The principal aim of this project is to obtain a better
      understanding of neurodiseases and aging with the ultimate objective of
      discovering prognostic and diagnostic biomarkers, in addition to the development
      of novel diagnostic techniques and new medications. The attendees came together
      to discuss progress in the clinical neuroproteomics of human and to define the
      needs and guidelines required for more advanced proteomics approaches.

PMID- 21717572
TI  - Quantitative phosphoproteomics reveals link between Helicobacter pylori infection
      and RNA splicing modulation in host cells.
AB  - The Gram-negative, spiral-shaped bacterium Helicobacter pylori is a common human
      pathogen that causes chronic inflammation of the human gastric mucosa, leading to
      peptic ulceration and/or gastric cancer. Here, we analyzed changes in the
      phosphoproteome of gastric epithelial cells (AGS) upon infection with H. pylori
      using a combination of SILAC, phosphoprotein enrichment, 2-DE, and MALDI TOF/TOF
      MS. From a total of 526 spots we identified 391 protein species (143 proteins)
      and quantified 332 (127 proteins). Nearly, one-third of the identified proteins
      (40/143) were associated with the spliceosome or RNA splicing. The abundance of
      20 proteins was altered by H. pylori infection, in particular, a number of serine
      arginine-rich (SR) proteins involved in the regulation and control of alternative
      splicing. Importantly, the combined methodologies enabled the detection of
      infection-dependent protein species-specific regulation, suggesting functional
      modulation of individual protein species. These findings reveal unexpected new
      insights into the mechanisms of host cell manipulation by H. pylori, which are
      likely associated with gastric pathologies, including gastric cancer.

PMID- 21717573
TI  - Proteomic profiling between CNE-2 and its strongly metastatic subclone S-18 and
      functional characterization of HSP27 in metastasis of nasopharyngeal carcinoma.
AB  - Metastasis to secondary sites remains the leading cause of nasopharyngeal
      carcinoma (NPC)-associated death. In order to identify the candidate protein(s)
      responsible for the differential metastatic capacity, the protein expression
      profiling between NPC cell line CNE-2 and its highly metastatic subclone S-18
      were compared by 2-DE. In total, 18 spots were differentially expressed between
      these two cell lines. Among all, seven proteins were identified with further MS
      analysis. Western blotting further validated upregulation of HSP27 and ezrin, and
      downregulation of valosin containing protein and keratin 18 in S-18. Moreover,
      the knockdown of HSP27 was found to significantly decrease the invasive ability
      of S-18. On the other hand, overexpression of HSP27 in NP460 cells, which
      generated little endogenous HSP27 and less invasive, was noted to gain enhanced
      metastatic capability. Real-time PCR confirmed that the transcriptional levels of
      NF-kappaB and MMP9, MMP11 were downregulated after inhibition of HSP27 in S-18,
      which implicated that HSP27 enhanced the metastatic property of NPC cells
      probably via the NF-kappaB-mediated activation of MMPs. The findings in this work
      provided us a platform for further elucidating the underlying mechanisms of NPC
      metastasis and demonstrated that HSP27 would be a valid target for anti-cancer
      drug development.

PMID- 21717574
TI  - Reaching across the disability divide: the case for collaboration with the
      disability community to construct a robust informed consent process around
      prenatal screening and diagnosis.

PMID- 21717576
TI  - Development of disulfide core-crosslinked pluronic nanoparticles as an effective
      anticancer-drug-delivery system.
AB  - Thiolated Pluronic (Plu-SH) nanoparticles are developed as potential articulate,
      target-specific anticancer-drug carriers for intracellular drug release triggered
      by the difference in redox potential in tumor cells. The cores of the micelles
      are formed by the disulfide bonds of the functionalized Pluronic F127, when
      dissolved in an aqueous solution. The nanoparticles are 95.6 +/- 18.6 nm in size,
      and 235.6 +/- 63.7 nm after encapsulation of the hydrophobic drug molecules. The
      drug-loaded micelles show effective stability in blood-plasma conditions and the
      kinetics of micelle stability and drug release are shown. Paclitaxel-loaded
      micelles display approximately 39% cell viability in A549 cells.

PMID- 21717577
TI  - Photoinduced reversible topographical changes on diarylethene microcrystalline
      surfaces with biomimetic wetting properties.
AB  - Reversible topographical changes were observed on a photochromic diarylethene
      microcrystalline film surface by alternate irradiation with UV and visible light.
      Two types of surfaces were prepared from this film: 1) Storage of the film at 30 
      degrees C for 24 hours in the dark after UV irradiation afforded a surface that
      was covered with needle-shaped crystals, whose diameter and length were
      approximately 1 MUm and 10 MUm, respectively, and showed a superhydrophobic lotus
      effect. 2) Storage of the film at 70  degrees C for 3 hours in the dark caused
      the needle-shaped crystals to be converted into larger rod-like crystals (5~8 MUm
      wide and 20~30 MUm long) by Ostwald ripening and a disappearance of the lotus
      effect. The obtained activation energy of the formation of the needle- and rod
      shaped crystals was 143 and 162 kJ mol(-1), respectively. Subsequent UV
      irradiation to the surface, which was followed by storage at 50  degrees C for 1
      hour in the dark, gave a doubly rough structure; small needle-shaped crystals
      were formed between the larger rod-shaped crystals. The surface showed both
      superhydrophobic properties and the pinned effect of the water droplet: the petal
      effect. Fractal analysis of both surfaces were carried out using a box-counting
      method, and the lotus effect was observed in the presence of smaller-sized
      crystals, whilst the petal effect was observed with larger sized crystals (ca.
      100 MUm). We demonstrated that the hydrophobic property was controlled by the
      distribution in crystal size of the closed-ring isomer of the diarylethene.
      Visible-light irradiation of both rough surfaces afforded surfaces with cubic
      shaped micro-crystals of the open-ring isomer.

PMID- 21717578
TI  - Anion-pi interactions in flavoproteins.

PMID- 21717579
TI  - Mitsunobu reaction of 1,2,3-NH-triazoles: a regio- and stereoselective approach
      to functionalized triazole derivatives.

PMID- 21717580
TI  - Fluorination reaction of a ditelluride bearing bulky aryl substituents: formation
      of mixed-valent Te(IV)-Te(II) ditelluride difluoride.

PMID- 21717581
TI  - Tin-based mesoporous silica for the conversion of CO2 into dimethyl carbonate.
AB  - Sn-based SBA-15 was prepared by reacting di-n-butyldimethoxystannane with SBA-15
      pretreated with trimethylchlorosilane (TMCS) to cap the external hydroxyl groups.
      Small-angle X-ray diffraction (SXRD), infrared spectroscopy (IR), nitrogen
      adsorption/desorption, transmission electron microscopy (TEM), thermogravimetric
      analysis (TGA), and inductively coupled plasma atomic emission (ICP-AES)
      measurements allow us to propose that the organotin species are located within
      the pore channels of the mesoporous host. This novel material catalyzes
      selectively the coupling of CO(2) with methanol to dimethyl carbonate (DMC). The
      reaction time-conversion dependence shows that a turnover number (TON) of 16 can
      be reached at 423 K under 20 MPa, which is among the highest reported so far in
      the absence of water traps. Moreover, as the catalytic activity is retained after
      recycling, even higher values can be obtained on a cumulative basis. A further
      TON increase is observed with the reaction temperature. Interestingly, the tin
      based SBA-15 mesoporous material exhibits lower TONs if the TMCS pretreatment is
      left out. Therefore, the organotin species located outside the channels are far
      less active than those located within.

PMID- 21717582
TI  - Ionic liquid catalysed synthesis of beta-hydroxy ketones.
AB  - Different acidic ionic liquids (ILs; namely, 1-methylimidazolium
      tetrafluoroborate, 1-methylimidazolium trifluoroacetate, N-methyl-2-pyrrolidone
      hydrogen sulfate, N,N,N-trioctyl-n-butanesulfonic acid ammonium hydrogen sulfate,
      1-methyl-3-(3-sulfobutyl)imidazolium hydrogen sulfate) and basic ILs (namely,
      1,1,3,3-tetramethylguanidinium lactate and choline hydroxide) were tested as
      catalysts for the aldol reaction. The choline hydroxide catalysed reaction gave
      high yield (94.3%) and selectivity of the 4-hydroxy-4-phenylbutan-2-one after a
      short reaction time (15 min) at 0  degrees C. This article demonstrates the
      potential of choline hydroxide, which is a derivative of choline and a naturally
      occurring water-soluble essential nutrient, as a highly active and selective
      green catalyst.

PMID- 21717583
TI  - 3-Deoxy-glucosone is an intermediate in the formation of furfurals from D
      glucose.

PMID- 21717584
TI  - Metformin induces G1 cell cycle arrest and inhibits cell proliferation in
      nasopharyngeal carcinoma cells.
AB  - It has been reported that metformin, a biguanide derivative widely used in type
      II diabetic patients, has antitumor activities in some cancers by activation of
      AMP-activated protein kinase (AMPK). But its role in nasopharyngeal carcinoma
      (NPC) is not known. Here, we reported for the first time that 1-50 mM of
      metformin in a dose- and time-dependent manner suppressed cell proliferation and
      colony formation in NPC cell line, C666-1. Further studies revealed that the
      protein level of cyclin D1 decreased and the percentage of the cells in G0/G1
      phase increased by 5 mM metformin treatment. Metformin also induced the
      phosphorylation of AMPK (T172) in a time-dependent manner. Mammalian target of
      rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a
      central role in cell growth and proliferation, was inhibited by metformin, as
      manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase
      1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding
      protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells. In a summary,
      metformin prevents proliferation of C666-1 cells by down-regulating cyclin D1
      level and inducing G1 cell cycle arrest. AMPK-mediated inhibition of mTORC1
      signaling may be involved in this process.

PMID- 21717585
TI  - The recent updates of therapeutic approaches against abeta for the treatment of
      Alzheimer's disease.
AB  - One of the main neuropathological lesions observed in brain autopsy of
      Alzheimer's disease (AD) patients is the extracellular senile plaques mainly
      composed of amyloid-beta (Abeta) peptide. Recently, treatment strategies have
      focused on modifying the formation, clearance, and accumulation of this
      potentially neurotoxic peptide. beta- and gamma-secretase are responsible for the
      cleavage of amyloid precursor protein (APP) and the generation of Abeta peptide.
      Treatments targeting these two critical secretases may therefore reduce Abeta
      peptide levels and positive impact on AD. Vaccination is also an advanced
      approach against Abeta. This review focuses on recent advances of our
      understanding of this key peptide, with emphasis on Abeta peptide synthesis,
      accumulation and neurotoxicity, and current therapies including vaccination and
      two critical secretase inhibitors. MicroRNAs (miRNAs) are a class of conserved
      endogenous small noncoding RNAs, known to regulate the expression of
      complementary messenger RNAs, involved in AD development. We therefore address
      the relationship of miRNAs in the brain and Abeta generation, as a novel
      therapeutic approach to the treatment of AD while also providing new insights on
      the etiology of this neurological disorder.

PMID- 21717586
TI  - Normal location of thumb/big toe may be related to programmed cell death in the
      preaxial area of embryonic limb.
AB  - The forelimbs and hindlimbs of newborn Polydactyly Nagoya (Pdn) mice were
      examined to analyze the roles of programmed cell death (PCD) in the preaxial
      region of the limb. Special attention was paid to the relationship between the
      PCD in the preaxial area and the location and shape of the first digit (thumb/big
      toe). Although a large, bifurcated or duplicated thumb/big toe appeared in Pdn/+
      mice, digit I (thumb/big toe) in Pdn/+ mice, as in +/+ ones, was located more
      ventro-proximally than the other four digits. On the other hand, abnormal
      preaxial digits of the fore/hindlimb in Pdn/Pdn mice lay distally and were
      aligned at the radial/tibial end of a serial curved plane formed by digits II-V;
      that is, a thumb and big toe of normal shape and location were not detectable in
      any preaxial digits of Pdn/Pdn mice. In the limb development of Pdn mouse embryos
      on Day 11-12, PCD did not occur in the preaxial mesoderm of fore/hindlimb only in
      one-fourths of all embryos obtained by Pdn/+ x Pdn/+ mating. In addition to
      digital rays II-V, extra preaxial digital rays appeared in the prominent preaxial
      expansion of fore/hindlimbs in these embryos on early Day 12. These abnormal limb
      configurations in embryos were closely similar to those in Pdn/Pdn newborn mice.
      The present findings suggest that PCD in the preaxial region not only prevents
      the formation of extra digits but also determines the location of the thumb/big
      toe for the normal limb morphogenesis.

PMID- 21717587
TI  - Development and expression of amyloid-beta peptide 42 in retinal ganglion cells
      in rats.
AB  - The previous studies have shown that amyloid-beta peptide (Abeta) was mainly
      found in neurons of neurodegenerative diseases, such as Alzheimer's disease (AD)
      and glaucoma and little is known about its expression in normal nerve cells. The
      aim of the present study was to investigate the expression of amyloid-beta
      peptide 42 (Abeta-42) in retinal ganglion cells of the postnatal rats. Rats were
      divided into seven experimental groups: 3, 6, 13, 15, 25, 60, and 90 days
      postnatal groups. Rats from 15 and 25 days postnatal groups were further divided
      into light-exposure and non light-exposure group. Cryosections or flat-mounted
      retinas of rat eyes were used for testing Abeta-42 by immunocytochemistry
      staining. Abeta-42 expression was not observed in rats within 13 days after
      birth, but was easily detectable in all groups of rats over 15 days after birth.
      In addition, the expression of Abeta-42 in retina was increasing as the rats got
      older, reached to highest level in 60 days after birth. Furthermore, the
      expression of Abeta-42 was not detected in rats kept under dark indicating that
      light is required for the expression of Abeta-42 in retina. This is the first
      report showing that normal retinal ganglion cells express Abeta-42, and that the
      expression of Abeta-42 in retinal ganglion cells requires the exposure to light.
      These data suggest that Abeta-42 may play a important role in vision development.

PMID- 21717588
TI  - Testing for human papillomavirus in cervical cancer screening: a review of
      indications and methodology.
AB  - High-risk human papillomavirus (hrHPV) testing has become an integral component
      of cervical cancer screening, given that persistent infection with hrHPV was
      recognized as a significant risk factor for most precancers and cancers of the
      cervix. Particularly, testing for hrHPV types (in conjunction with cervical
      cytology) has been approved for primary screening in women over 30 years of age
      and for cost-effective triaging of equivocal cervical cytology results. HPV was a
      small double-stranded DNA virus that cannot be cultured in vitro; so, different
      types of tests have been developed to detect its presence. Various molecular
      techniques were available for detecting the presence and/or quantity of hrHPV. In
      this review, the testing options for hrHPV and its surrogates, with an emphasis
      on those approved by the US Food and Drug Administration (FDA), were detailed.
      Cancer (Cancer Cytopathol) 2011;. (c) 2011 American Cancer Society.

PMID- 21717589
TI  - Comparison of the expression levels of napsin A, thyroid transcription factor-1,
      and p63 in nonsmall cell lung cancer using cytocentrifuged bronchial brushings.
AB  - BACKGROUND: Appropriate treatment of nonsmall cell lung cancer (NSCLC) depended
      on histologic type. The aim of this study was to evaluate the expression levels
      of Napsin A, thyroid transcription factor-1 (TTF-1), and p63 by immunostaining
      using CytoRich Red preserved cytocentrifuged bronchial brushings. METHODS: The
      expression levels of Napsin A, TTF-1, and p63 were semiquantitatively evaluated
      using proportion and intensity scores in 12 patients from whom both bronchial
      brushing cytology and bronchial biopsy samples had been obtained, as well as in a
      selection of 64 resected NSCLC tissue samples, and 8 normal or benign bronchial
      brushing cytology samples. RESULTS: The nuclear expressions of TTF-1 and p63
      allowed for good visualization of cancer cells, whereas the cytoplasmic
      expression of Napsin A in cancer cells was often more difficult to evaluate
      because medium-sized and large macrophages also expressed Napsin A. Napsin A and
      TTF-1 were reliable adenocarcinoma markers, and p63 was a reliable squamous cell
      carcinoma marker in cytology, and histology samples. The average scores of Napsin
      A, TTF-1, and p63 were highly correlated in bronchial brushing cytology and
      bronchial biopsy samples, whereas TTF-1 expression was significantly lower than
      Napsin A expression in resected NSCLC tissue samples (P < .001). CONCLUSIONS:
      Immunostaining of bronchial brushings fixed with CytoRich Red was useful in
      determining histologic types in NSCLC. It was suggested that the panels of Napsin
      A, TTF-1, and p63 were effective in identifying histologic type in NSCLC, and
      that a combination of either Napsin A and p63 or TTF-1 and p63 should be chosen,
      depending on morphology.

PMID- 21717590
TI  - Maximizing the yield of lymph node cytology: Lessons learned from rapid onsite
      evaluation of image- and endoscopic-guided biopsies of hilar and mediastinal
      lymph nodes.
AB  - The evaluation of mediastinal and hilar lymph nodes for tissue diagnosis and
      staging of lung cancer is now commonly performed by minimally invasive,
      nonsurgical procedures such as computed tomography-guided fine-needle aspiration
      and endobronchial ultrasound-guided transbronchial needle aspiration. Ensuring
      that a sufficient quantity of cellular material has been acquired to enable
      multiple studies has become a priority issue in the era of personalized medicine,
      especially for patients with lung cancer, and this can be accomplished by rapid
      onsite evaluation (ROSE). This commentary focuses on the use of ROSE in guided
      procedures, especially for hilar and mediastinal lymph node aspirates, and
      describes an algorithm for handling these specimens.

PMID- 21717591
TI  - Identification of tissue of origin in body fluid specimens using a gene
      expression microarray assay.
AB  - BACKGROUND: Body fluid specimens may be the first and only pathologic specimen
      for clinical evaluation in metastatic cancer cases. The challenge of identifying
      the tissue of origin in metastatic cancer has led to the emergence of molecular
      based assays, such as the microarray-based Pathwork Tissue of Origin gene
      expression test. The ability to use body fluid specimens in this test would be
      valuable in providing diagnoses to cancer patients without clearly identifiable
      primary sites. In the current study, the authors evaluated the Tissue of Origin
      Test for use with malignant effusion specimens. METHODS: A total of 27 metastasis
      positive body fluid specimens from different body sites, including pleural,
      ascites, pericardial, and pelvic wash fluids, were obtained from patients with
      known diagnoses. Nine specimens from nonmalignant body fluids were included as
      controls. RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue
      and gene expression analysis was performed with the Tissue of Origin Test.
      RESULTS: Seventeen of 27 metastasis-positive samples were non-necrotic with >=60%
      tumor and yielded sufficient RNA. Of these samples, 94.1% (16 of 17) were in
      agreement with the available diagnosis. Of the 9 negative control samples
      evaluated, 7 (77.8%) demonstrated microarray expression profiles most similar to
      lymphoma, which is consistent with the predominance of inflammatory cells in
      these specimens. CONCLUSIONS: The results of the current study demonstrated that
      FFPE cell blocks from cytologic body fluid specimens yield adequate diagnostic
      material for the Pathwork test and can be used in the workup of patients with
      unknown primary tumors.

PMID- 21717592
TI  - A multicolor fluorescence in situ hybridization assay: A monitoring tool in the
      surveillance of patients with a history of non-muscle-invasive urothelial cell
      carcinoma: A prospective study.
AB  - BACKGROUND: Non-muscle-invasive urothelial cell carcinoma (NMIUCC) has a high
      tendency to recur and affected patients must be monitored regularly using
      invasive cystoscopies. The aim of the current study was to compare a multicolor
      fluorescence in situ hybridization (FISH) assay (UroVysion) with routine follow
      up (cystoscopy and cytology) in the monitoring of patients with a previous
      history of NMIUCC. METHODS: An unselected cohort of patients under surveillance
      for a previous history of NMIUCC was prospectively studied. A total of 248
      examinations in 223 patients were analyzed. Each exploration was comprised of
      cytological and FISH microscopic examination of voided urine samples and
      cystoscopy. The sensitivity, specificity, and positive (PPV) and negative (NPV)
      predictive values for tumor recurrence of all 3 techniques were determined.
      RESULTS: The sensitivities of FISH and cystoscopy were not found to be
      significantly different (92.9% and 82.1%, respectively). The specificities of
      FISH and cystoscopy were 92.7% and 89.7%, respectively. The PPV and NPV of FISH
      were 53.5% and 97.2%, respectively, whereas those of cystoscopy were 63.4% and
      98.9%, respectively. No significant differences were found between these 2 tests.
      In contrast, the sensitivity and specificity of cytology were 14.3% and 99.5%,
      respectively. CONCLUSIONS: Given the lack of statistically significant
      differences with regard to FISH and cystoscopy results, the authors propose that
      FISH could be a useful monitoring tool in the surveillance of patients with a
      previous history of NMIUCC.

PMID- 21717593
TI  - Resident teachers in anatomy: valuable asset! Endangered species?

PMID- 21717595
TI  - Arthritis care & research: continued success and evolution.

PMID- 21717596
TI  - American College of Rheumatology provisional criteria for defining clinical
      inactive disease in select categories of juvenile idiopathic arthritis.
AB  - OBJECTIVE: To prospectively validate the preliminary criteria for clinical
      inactive disease (CID) in patients with select categories of juvenile idiopathic
      arthritis (JIA). METHODS: We used the process for development of classification
      and response criteria recommended by the American College of Rheumatology Quality
      of Care Committee. Patient-visit profiles were extracted from the phase III
      randomized controlled trial of infliximab in polyarticular-course JIA (i.e.,
      patients considered to resemble those with select categories of JIA) and sent to
      an international group of expert physician raters. Using the physician ratings as
      the gold standard, the sensitivity and specificity were calculated using the
      preliminary criteria. Modifications to the criteria were made, and these were
      sent to a larger group of pediatric rheumatologists to determine quantitative,
      face, and content validity. RESULTS: Variables weighted heaviest by physicians
      when making their judgment were the number of joints with active arthritis,
      erythrocyte sedimentation rate (ESR), physician's global assessment, and duration
      of morning stiffness. Three modifications were made: the definition of uveitis,
      the definition of abnormal ESR, and the addition of morning stiffness. These
      changes did not alter the accuracy of the preliminary set. CONCLUSION: The
      modified criteria, termed the "criteria for CID in select categories of JIA,"
      have excellent feasibility and face, content, criterion, and discriminant
      validity to detect CID in select categories of JIA. The small changes made to the
      preliminary criteria set did not alter the area under the receiver operating
      characteristic curve (0.954) or accuracy (91%), but have increased face and
      content validity.

PMID- 21717597
TI  - Association of flat feet with knee pain and cartilage damage in older adults.
AB  - OBJECTIVE: To assess the cross-sectional relation of planus foot morphology to
      ipsilateral knee pain and compartment-specific knee cartilage damage in older
      adults. METHODS: In the Framingham Studies, we adapted the Staheli Arch Index
      (SAI) to quantify standing foot morphology from pedobarographic recordings. We
      inquired about knee pain and read 1.5 T magnetic resonance image (MRI) scans
      using the Whole-Organ MRI Score. Logistic regression compared the odds of knee
      pain among the most planus feet to the odds among all other feet, and estimated
      odds within categories of increasing SAI. Similar methods estimated the odds of
      cartilage damage in each knee compartment. Generalized estimating equations
      adjusted for age, sex, body mass index, and nonindependent observations. RESULTS:
      Among 1,903 participants (56% women, mean +/- SD age 65 +/- 9 years), 22% of
      knees were painful most days. Cartilage damage was identified in 45% of medial
      tibiofemoral (TF), 27% of lateral TF, 58% of medial patellofemoral (PF), and 42%
      of lateral PF compartments. Compared with other feet, the most planus feet had
      1.3 times (95% confidence interval [95% CI] 1.1-1.6) the odds of knee pain (P =
      0.009), and 1.4 times (95% CI 1.1-1.8) the odds of medial TF cartilage damage (P
      = 0.002). Odds of pain (P for linear trend = 0.05) and medial TF cartilage damage
      (P for linear trend = 0.001) increased linearly across categories of increasing
      SAI. There was no association between foot morphology and cartilage damage in
      other knee compartments. CONCLUSION: Planus foot morphology is associated with
      frequent knee pain and medial TF cartilage damage in older adults.

PMID- 21717598
TI  - Exposure to international migration and its effect on childbearing in Turkey.
AB  - International migration alters social norms, family structures, and population
      development in sending regions. Each of these factors affects fertility, making
      the impact of international migration on childbearing an increasingly important
      area of study. In many sending regions, the Demographic and Health Surveys (DHS)
      provide a promising, but underutilized, source of data for understanding the
      relationship between international migration and childbearing. Using the
      household and individual questionnaires in the 2003 Turkish DHS, we develop a
      multi-layered approach for measuring international migration. We then use these
      measures to examine differences in childbearing among women in migrant and non
      migrant households, assessing the effects of migrant selection and migration
      related roles and attitudes on the number of children born. After adjusting for
      selection characteristics, we find return female migrants and migrant wives are
      not significantly different from women in non-migrant households; role and
      attitude differences have only modest impacts on the association between women's
      exposure to migration and childbearing.

PMID- 21717599
TI  - Creating egalitarian families among the adult children of Turkish- and Polish
      origin immigrants in Sweden.
AB  - This article analyzes the factors shaping egalitarian family relationships among
      those with two Swedish-born parents and those with at least one parent born in
      Poland or Turkey. We ask: (1) What factors affect sharing domestic tasks and do
      they also shape the division of child care responsibilities? (2) Do these effects
      differ, depending on the extent of exposure to Swedish life? We analyze data from
      a longitudinal survey conducted between 1999 and 2003. Holding egalitarian work
      family attitudes affects actual sharing of housework, but much more for those
      growing up in more socially integrated than in less integrated families.

PMID- 21717600
TI  - [Physiological processes in organism: nanomechanism].
AB  - Physiologically active substances by nanosizes are divided into 4 groups. The
      first group includes substances up to 100 nm: leukocytes, erythrocytes, cell
      components (nucleus, mitochondria), cancer cells, bacteria and bacteriophages.
      The second group consists of nanoparticles with size from 10 to 100 nm. These are
      antibody, ribosomes, glycogen granules, liposomes, and others. The third group of
      substances has sizes from 10 to 1 nm. This group includes: albumin, hemoglobin,
      membrane cells, fibrixogen, receptors (serotonin, beta-adrenergic receptor and
      others), insulin, fat soluble vitamins (ergocalciferol, retinol), folic acid,
      drugs (digoxin, quetcitin), chlorophyll plants, fullerenes. The fourth group
      consists of matter smaller than 1 nm, in particular: ATP, fructose, mediators
      (acetyl-choline, adrenaline, noradrenaline), phenylephrine, amino acids, water
      molecules, CO2, NO, oxygen atoms, hydrogen. The existence in the body of
      physiological processes based on natural nanotechnology may be proved by the
      following facts. 1. Physiologically active substances have nanosizes. 2. Cell
      membranes, the capillary wall have also nanosizes, promoting effective
      physiological processes involving biologically active substances with nanosizes.
      3. Due to the small size of nanoparticles can penetrate through cell membranes
      and be distributed in the body. 4. From the position of modern nanoscience
      functioning organs, cells, subcellular structures, calcium channels, sodium
      potassium pump is under the laws of natural nanomechanisms. 5. Summarising the
      literature data and own research, we can argue that the body's physiological
      processes based on natural nanomechanisms require more detailed, in-depth
      research. Nanophysiology studies peculiarities of the physiological processes in
      the body from the position of nanoscience and the impact of nanoparticles on the
      function of cells and organs. The author accepts the fact that not all ideas
      reported in this article have experimental confirmations, discussion is necessary
      for further comprehensive research, specialists of different directions to
      discover the role of nanomechanismes in physiological processes in the body.

PMID- 21717601
TI  - [Main issues of diagnosis and treatment of lymphomas in Ukraine].
AB  - Number of patients with lymphomas in Ukraine increases annual. The increase of
      morbidity during 2007-2008 years is 4.3-8.1%. The rate of effectiveness of the
      treatment and patient's survival in Ukraine is lower then the world rate.
      Overview of main issues of the lymphoma's diagnosis and treatment in Ukraine is
      presented in this article.

PMID- 21717602
TI  - [Characteristics of motor, cognitive, and emotional manifestations depending on
      the clinical variant of Parkinson's disease].
AB  - As a result of Parkinson's disease patients investigation, and their division on
      groups depending on prevalence of akinesia and rigidity or tremor, dependence of
      cognitive and emotional disturbances on motor variant of Parkinson's disease is
      revealed.

PMID- 21717603
TI  - Violence against women. Editor's introduction.

PMID- 21717604
TI  - Comments on Point:Counterpoint: Muscle lactate and H+ production do/do not have a
      1:1 association in skeletal muscle. Calculations of Robergs support the view of
      Vinnakota and Kushmerick.

PMID- 21717605
TI  - Comments on Point:Counterpoint: Muscle lactate and H+ production do/do not have a
      1:1 association in skeletal muscle. No evidence for the Counterpoint position.

PMID- 21717606
TI  - Comments on Point:Counterpoint: Muscle lactate and H+ production do/do not have a
      1:1 association in skeletal muscle. Why add complexity/confusion to a simple
      issue?

PMID- 21717607
TI  - Comments on Point:Counterpoint: Muscle lactate and H+ production do/do not have a
      1:1 association in skeletal muscle. Confusion concerning the lactate proton
      ratio: a problem of definition?

PMID- 21717608
TI  - Comments on Point:Counterpoint: Muscle lactate and H+ production do/do not have a
      1:1 association in skeletal muscle. Lactate and acidosis yet again?

PMID- 21717609
TI  - Comments on Point:Counterpoint: Muscle lactate and H+ production do/do not have a
      1:1 association in skeletal muscle. Lactate and acidosis yet again?

PMID- 21717610
TI  - Comments on Point:Counterpoint: Muscle lactate and H+ production do/do not have a
      1:1 association in skeletal muscle. Lactate and acidosis yet again?

PMID- 21717611
TI  - First seizure in a young woman.

PMID- 21717612
TI  - Intracranial mass causing seizures.

PMID- 21717613
TI  - Biomedical ontologies: toward scientific debate.

PMID- 21717614
TI  - First thoughts. Different ways to deliver.

PMID- 21717615
TI  - Best practice. Bright ideas for better care.

PMID- 21717616
TI  - Telehealth. Miles ahead.

PMID- 21717617
TI  - Final thoughts. A call to action.

PMID- 21717618
TI  - Introduction. A new approach.

PMID- 21717619
TI  - Assessment and care planning. Forward planning.

PMID- 21717620
TI  - Health and wellbeing clinics. A way out of limbo.

PMID- 21717621
TI  - Supported self management. Meet the activated patient.

PMID- 21717622
TI  - Long term consequences of treatment. Illnesses that are overlooked.

PMID- 21717623
TI  - Vocational rehabilitation. A job that is worth doing well.

PMID- 21717624
TI  - Physical activity. Good moves.

PMID- 21717625
TI  - The future. The whole package.

PMID- 21717626
TI  - National VTE prevention programme. Deaths we can avoid.

PMID- 21717627
TI  - Commissioning. What does good care look like?

PMID- 21717628
TI  - Best practice. A real kitemark of excellence.

PMID- 21717629
TI  - Diametrically opposed.
AB  - As states continue to grapple with rising healthcare costs and budget
      constraints, two have set themselves on divergent paths. In Vermont, Gov. Peter
      Shumlin, left, is set to sign a bill that would steer the state toward a single
      payer system in which residents will have their care paid for out of a single
      fund. Meanwhile, Florida is on the verge of turning its Medicaid program into a
      managed-care system to be overseen by private insurers.

PMID- 21717630
TI  - Reduce or revise. Medicaid scrutinized as both sides look for cuts.

PMID- 21717631
TI  - Arguments begin. Federal appeals judges grill Va. ACA opponents.

PMID- 21717632
TI  - Moving on. Community, tenet battle ends, but effects linger.

PMID- 21717633
TI  - Sour note on ACOs. AMGA endorsed concept, but hates proposed regs.

PMID- 21717634
TI  - A different kind of offer. WakeMed bids for rival, cites state budget woes.

PMID- 21717635
TI  - Attention, please. Reports spotlight quality, patient-safety concerns at nursing
      homes.

PMID- 21717636
TI  - Pay loses its perk.

PMID- 21717637
TI  - Largest children's hospitals. Ranked by number of staffed beds, based on the
      latest CMS report from each facility.

PMID- 21717638
TI  - Sticker shock. Despite benefits of using Medicare's claims data, the price may
      force many to pass it by.
AB  - The CMS is ready to offer claims data to groups producing quality reports, but
      the hefty price tag could be a big obstacle. "We see the audience for this
      information as a cross section of stakeholders. I'm assuming CMS has the same
      interests and would benefit. I hope that over time, as they see the value, those
      costs might be reduced or eliminated," says Mylia Christensen of the Oregon
      Healthcare Quality Corp.

PMID- 21717639
TI  - Following Blue Shield's lead. Will move to cap profits inspire other insurers?

PMID- 21717640
TI  - Tough questions. Court questions whether mandate can reach goal.

PMID- 21717641
TI  - HMA makes a switch. Chain no longer uses software linked to CHS suit.

PMID- 21717642
TI  - Planning for the future through IT. North Shore-LIJ's Dowling leads rollout of
      ambitious EHR program.

PMID- 21717643
TI  - For this CEO, IT helps drive performance. Gribbin says technology is a means to
      his greater goal: seeing staff succeed.

PMID- 21717644
TI  - The burden of privacy? Demands placed by proposed privacy rule could outweigh
      patient benefits.

PMID- 21717645
TI  - Most prescribed pharmaceuticals. Ranked by total number of retail prescriptions,
      2010 (numbers in millions).

PMID- 21717646
TI  - Asleep at the switch.
AB  - Two new reports had some harsh words for HHS' enforcement of the HIPAA security
      rule on guarding patient data. A lack of strong enforcement may be hindering
      providers' efforts in the area. "I continue to hear from folks who work in
      security, that as long as there is not visible enforcement, it hurts their
      chances to getting the resources and budgets and employees they need," says Lisa
      Gallagher.

PMID- 21717647
TI  - Cost-benefit ratio. GOP isn't alone in pushing for Medicare changes.

PMID- 21717648
TI  - On the fast track. Pioneer model to kick-start ACOs.

PMID- 21717649
TI  - Rate review standoff. Final rule irks both insurers, consumer advocates.

PMID- 21717651
TI  - Targeting prevention. We might never know the true benefits of efforts to improve
      public health.

PMID- 21717650
TI  - IT, docs focus of investments.

PMID- 21717652
TI  - Challenged journey. Despite partisan conflict and mandates, healthcare insurance
      is a lifeline.

PMID- 21717653
TI  - Helping hands.

PMID- 21717654
TI  - Candid cameras. Video ethnography helping improve patient care.

PMID- 21717655
TI  - After the storm.
AB  - The tornado that whipped a path of devastation through Joplin, Mo., left one of
      its hospitals in tatters. But the view from St. John's Regional Medical Center,
      at left, is tinged with hope as officials plan for rebuilding. "It will be a
      wonderful opportunity to reimagine" how to provide healthcare in Joplin, says
      Lynn Britton, CEO of parent company Sisters of Mercy Health System.

PMID- 21717656
TI  - GOP deficit plan gone ... but cuts to Medicare, Medicaid likely to stay.

PMID- 21717657
TI  - Funding single payer. As Vermont paves way to reform, hurdles remain.

PMID- 21717658
TI  - Paging Dr. Superstar. Docs urged to adopt habits that lead to optimal care.

PMID- 21717659
TI  - Early discharge. Poor care cited in ruling to release Calif inmates.

PMID- 21717660
TI  - Navigating ACOs.

PMID- 21717661
TI  - A preventive approach. Community health centers work to block cuts.

PMID- 21717662
TI  - Thomson Reuters' 10 top health systems study.

PMID- 21717663
TI  - [Hematologic malignancies/ pediatric malignancies-chronic myeloid leukemia].

PMID- 21717664
TI  - [Computer tailoring: a potential solution for optimizing prevention counseling].
AB  - Scientific literature shows that physicians who engage in clinical prevention
      practices (CPP) have an influence on population health. This is why they are
      encouraged to apply such practices to promote healthy lifestyle habits in their
      patients, such as exercise, a healthy diet, and smoking cessation. However, as
      revealed in a recent study published in the Canadian journal of Public Health,
      lack of time is the main barrier for doctors in applying CPP. Following upon the
      results presented in their study, the authors suggest certain solutions that are
      likely to facilitate prevention practices. The goal of this commentary is to
      familiarize readers with another potential solution, relatively unknown in
      Canada, namely computer-tailoring. This innovative intervention method has the
      potential to facilitate prevention counselling because it provides a means of
      interacting with a large audience by formulating "customized" educational
      messages for each member.

PMID- 21717665
TI  - [The impact of opening a heroin-assisted treatment clinic on the surrounding
      neighborhood].
AB  - OBJECTIVES: Heroin-assisted treatment clinics are currently the focus of a social
      debate. In spite of the clinics' effectiveness in reducing illicit opiate use,
      some decision-makers refuse to set them up because of their possible negative
      impact. These clinics could attract new drug users into the neighbourhood which
      could lead to an accumulation of injection debris and to a decrease in the sense
      of security in the community. This study assesses the impact on some elements
      observed in the surrounding community following the opening of the Montreal
      heroin-assisted treatment clinic. METHODS: Ethnographical walks were taken in
      order to collect data on the amount of injection debris, street debris and
      deviant activities. Data were then aggregated on a daily basis and our
      interrupted time series were analyzed using the segmented regression methodology.
      RESULTS: Results show that the opening of the clinic was followed by a
      significant drop in the amount of injection and street debris. This reduction
      appears proportional to the number of clinic participants. CONCLUSION: The
      Montreal heroin-assisted treatment clinic did not produce any negative impact on
      the surrounding community. In fact, implementation of this kind of clinic was
      followed by a positive effect on the neighbourhood. In addition to the
      ethnographical walks, further studies should include surveys in order to estimate
      the impact of heroin-assisted treatment clinics on residents' sense of security.
      Even if there appears to be a positive impact, it is possible that the mere
      presence of these clinics negatively affects community members' sense of
      security.

PMID- 21717666
TI  - [Humanitarian ethics and the concept of justice].
AB  - The bases of humanitarian assistance, beyond a legal norm--which appears to be
      essential given the inalienable obligations that result for all participating
      bodies--are influenced by philosophical and political conceptualizations framed
      in an ethics of justice. Actors in the humanitarian field who adhere to the
      Rawlsian social contract model their actions based on a philosophy that
      assistance is a noble and desirable option that remains in the hands of those who
      offer aid, and who can freely choose to not offer such assistance. Peter Singer
      and Thomas Pogge propose nuances to the understanding of the duty of assistance.
      Not assisting would be bad, basically tantamount to killing. Assistance is no
      longer a caring act deserving of praise, but rather a moral obligation. The
      financial imperatives of associations, the growing complexity of activities and
      the development of an important element of communication lead to a
      professionalization of humanitarian medicine. A modern vision of humanitarian
      assistance requires an understanding of justice and solidarity and global
      outreach. We believe that ethics need to be embedded firmly in humanitarian
      actions that have clear political implications.

PMID- 21717667
TI  - [The National Association of Nurses at the heart of the storm].

PMID- 21717668
TI  - [After the earthquake, mobilization of the Japanese Red Cross].

PMID- 21717669
TI  - [Organ donation beyond religious beliefs].

PMID- 21717670
TI  - [Patient rights, what changes in 2011?].

PMID- 21717671
TI  - [From the physiology of pain to an antihyperalgesic nutritional approach].
AB  - Pain is brought into play by a system which detects and transmits messages
      signaling pain. Opioids negatively modulate nociception, but paradoxically also
      contribute to hyperalgesia. A nutritional approach with low polyamine contents
      helps to reduce this phenomenon without the harmful side effects of
      antihyperalgesic drugs.

PMID- 21717672
TI  - [Preventing burnout in nursing students].
AB  - In 2009-2010, four "personal development and stress management" workshops were
      attended by all the 2nd and 3rd year students at the nursing training institute
      of Sainte-Marguerite Hospital in Marseille. Beforehand, their stress levels were
      assessed using the Maslach Burnout Inventory (MBI) scale which revealed that such
      a workshop would be useful. 80% of students were interested and 50% found it to
      be of real help. This work involves reflecting on the malaise among healthcare
      professionals and the ways of overcoming it.

PMID- 21717673
TI  - [The place of paramedics in the drawing up of good practice guidelines].
AB  - It is essential that paramedics take part in the drawing up of good practice
      guidelines. These recommendations are aimed at guiding all healthcare
      professionals to provide global care to the patient. Enabling such collaboration
      allows the expertise of paramedical staff to be recognised and encourages
      exchanges and awareness of research on new practices.

PMID- 21717674
TI  - [Better management of vulnerable populations].

PMID- 21717675
TI  - [Different sociological aspects of vulnerability].

PMID- 21717676
TI  - [For the network between medical and social fields].

PMID- 21717677
TI  - [Illnesses of vulnerable populations].

PMID- 21717678
TI  - [Inter-disciplinary collective skills for the benefit of people in extreme
      precarity].
AB  - The specificity of the provision of care to the most deprived people lies in the
      "caring". It implies global care which brings into play a medical-psychological
      social synergy.

PMID- 21717679
TI  - [Exclusion and the aged, a vulnerable health status].

PMID- 21717680
TI  - [Hypothermia in people in situations of precarity].
AB  - Human beings are physiologically warm blooded. Confronted with extreme cold, they
      become subject to hypothermia. Between a mountain climber and a person living in
      the street, the functions of resistance to a drop in external temperature are not
      the same. Studies on this subject remain to be carried out.

PMID- 21717681
TI  - [Migrants' health, the experience of a network providing access to healthcare].
AB  - Migrants form a heterogeneous population which requires specific medical-social
      care. Networks providing access to healthcare are one of the solutions enabling
      migrants to benefit from curative and preventative primary care.

PMID- 21717682
TI  - [Teams working at the heart of precarity].
AB  - The specific mission of the Nanterre hospital and nursing home (CASH) is to
      welcome, care for and accommodate people in situations of precarity. To fulfil
      this mission, multi-professional teams from the healthcare and social sector work
      there.

PMID- 21717683
TI  - [A night at Samusocial, testimony of a caregiver].

PMID- 21717684
TI  - [Mental health and addictions in homeless people].
AB  - The prevalence of psychiatric disorders and addictions to alcohol, drugs or the
      improper use of prescription medicines in homeless people raises the question-
      what is the reality on the ground? What type of care is currently available for
      these problems of psychological suffering and what reflections and perspectives
      do they incite?

PMID- 21717685
TI  - [The psychological consequences of precarity].
AB  - Psychological suffering does not just effect people in a situation of exclusion
      and precarity. However, it does assume in these people considerable importance,
      representing profound suffering and hampering their efforts to reintegrate into
      society. Re-establishing a sociallink and putting in place support networks are
      two solutions to implement.

PMID- 21717686
TI  - [Welfare benefits].
AB  - Since 1928, a range of social policies to fight against poverty have been
      developed. There are many different types of benefits and people need to be well
      informed. The social worker plays a key role in supporting and guiding people
      through all the types of benefits available.

PMID- 21717687
TI  - [The evils of the street].

PMID- 21717688
TI  - [Decoding body language to anticipate stress].

PMID- 21717689
TI  - [Trends in cardiology].

PMID- 21717690
TI  - [Coronary artery disease diagnostic with fractional flow reserve].
AB  - Fractional flow reserve (FFR) is an invasive pressure-derived index of epicardial
      stenosis severity used in the catheterization laboratory to assess the
      hemodynamic significance of coronary lesions when non-invasive functional
      assessment has either not been performed or is inconclusive. The use of invasive
      coronary physiology has demonstrated favorable outcomes for decision making in
      patients with intermediate single-vessel disease, with left main stenosis,
      complex bifurcations lesions and multivessel coronary artery disease.
      Specifically, in patients with stable angina revascularization with either
      percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)
      surgery should be deferred for epicardial coronary stenosis with an FFR > 0.8.

PMID- 21717691
TI  - [Mechanical complications of myocardial infarction].
AB  - Despite a marked reduction in mortality after myocardial infarction during the
      last decades thanks to heart monitoring and early reperfusion, there remains a
      significant rate of in-hospital mortality. This is a consequence of refractory
      ventricular dysfunction in most cases, or mechanical complications of myocardial
      infarction in the remaining cases. Mechanical complications include septal
      rupture with ventricular septal defect, tamponnade following rupture of the left
      ventricular free wall, and acute mitral regurgitation due to papillary muscle
      infarction and rupture. Although these complications are rare, their prognosis is
      very poor. An early detection of clinical signs of mechanical complications is
      crucial to urgently precise the diagnosis by echocardiography and subsequently
      plan the most appropriate medico-surgical management.

PMID- 21717692
TI  - [Cardiac MRI in the follow-up of adult congenital cardiomyopathy patients].
AB  - Magnetic resonance imaging is a rapidly developing modality in cardiology. It
      offers an excellent image definition and a large field of view, allowing a more
      accurate morphological assessment of cardiac malformations. Due to its unique
      versatility and its ability to provide myocardial tissue characterization,
      cardiac magnetic resonance (CMR) is now recognized as a central imaging modality
      for a wide range of congenital heart diseases, including assessment of post
      surgical cardiac anatomy, quantification of valvular disease and detection of
      myocardial ischemia. CMR provides useful diagnostic information without any
      radiation exposure, and improves the global management of patients with
      congenital heart disease.

PMID- 21717693
TI  - [Specificities of diabetes in acute coronary syndromes].
AB  - Contrary to the decline in the prevalence of several risk factors such as
      hypertension, hypercholesterolemia and smoking, diabetes is an expanding health
      burden in the western world. Because of the proatherosclerotic, proinflammatory,
      and prothrombotic states associated with diabetes, diabetic patients with acute
      coronary syndromes (ACS) are at high risk of subsequent cardiovascular events.
      However, they derive greater benefit from aggressive platelet inhibition and an
      early invasive strategy than non-diabetic individuals. Despite the documented
      efficacy, diabetic patients with ACS receive evidence-based treatments less
      frequently than non-diabetic individuals.

PMID- 21717694
TI  - [Transcatheter aortic valve implantations in 2011: the interventional
      cardiologist].
AB  - Since the first transcatheter aortic valve implantation 9 years ago, constant
      technological progress and simplification of the procedure have been observed.
      For two devices in particular (Edwards SAPIEN valve and CoreValve), considerable
      clinical experience has been gained, with over 17,000 implantations each. The
      safety and efficacy of this technique have recently been confirmed in the
      randomized trial Partner. Consequently, the end of 2010 saw the TAVI
      (Transcatheter aortic valve implantation) become the standard-of-care for
      selected patients deemed inoperable on the basis of age or co-morbidities and now
      is an acceptable alternative to surgery in selected high-risk operable patients.
      However, the selection of patients and the technique used (trans-arterial or
      trans-apical) require a multidisciplinary approach which remains essential for
      procedural success.

PMID- 21717695
TI  - [Selection and preoperative follow-up of heart transplantation candidates in the
      French part of Switzerland].
AB  - Heart transplantation (HTx) started in 1987 at two university hospitals (CHUV,
      HUG) in the western part of Switzerland, with 223 HTx performed at the CHUV until
      December 2010. Between 1987 and 2003, 106 HTx were realized at the HUG resulting
      in a total of 329 HTx in the western part of Switzerland. After the relocation of
      organ transplantation activity in the western part of Switzerland in 2003, the
      surgical part and the early postoperative care of HTx remained limited to the
      CHUV. However, every other HTx activity are pursued at the two university
      hospitals (CHUV, HUG). This article summarizes the actual protocols for selection
      and pre-transplant follow-up of HTx candidates in the western part of
      Switzerland, permitting a uniform structure of pretransplant follow-up in the
      western part of Switzerland.

PMID- 21717696
TI  - [Bipolar disorder and attention deficit/hyperactivity disorder in adults:
      differential diagnosis or comorbidity].
AB  - Attention deficit/hyperactivity disorder (ADHD) can sometimes coexist with
      bipolar disorder (BD). Despite controversies about the coexistence of the two
      disorders, recent clinical as well as biological studies support the concept of
      comorbid adult ADHD and BD. Although there is some overlapping symptomatology
      between both disorders, ADHD can be diagnosed in patients suffering from with BD
      after a detailed clinical evaluation. Clinicians should be particularly attentive
      to specific symptoms in order to treat adequately both disorders since untreated
      ADHD comorbidity with BD is associated with poor clinical and socio-professional
      outcome.

PMID- 21717697
TI  - [The Swiss and regenerative medicine: towards an early commitment].

PMID- 21717698
TI  - [Who are those who "wallow in sex"? ].

PMID- 21717699
TI  - [Health insurance: solidarity threatened].

PMID- 21717700
TI  - [A recipe for becoming tubercular].

PMID- 21717701
TI  - [Confusion in hospital financing].

PMID- 21717702
TI  - [Which organs are involved here? Erdheim-Chester disease].

PMID- 21717703
TI  - [Patient with diabetes mellitus: how much alcohol may he have?].

PMID- 21717704
TI  - [Obesity costs 7 years of life: what controls the fat overload?].

PMID- 21717705
TI  - [Naturopathy consultation. Cervical syndrome].

PMID- 21717706
TI  - [5 recommendations for better medicine].

PMID- 21717707
TI  - [Unwelcome souvenirs of the holidays in tropical regions].

PMID- 21717708
TI  - [Skin disorder after returning from a tropical country].

PMID- 21717709
TI  - [Fever in travelers returning from the tropics: outpatient management].

PMID- 21717710
TI  - [Emergency checklist: burns in children].

PMID- 21717711
TI  - [Constipation--hard stool, soft data].

PMID- 21717712
TI  - [Intentional carbon monoxide poisoning by burning charcoal].

PMID- 21717713
TI  - [Options of NO substitution: proven and future methods. A pharmaceutical classic
      on the upswing].

PMID- 21717714
TI  - [Pain therapy with opioids following WHO treatment guidelines].

PMID- 21717715
TI  - [Angina pectoris: improving symptoms and prognosis. With ivabradine less angina
      pectoris and reduced need for nitrates].

PMID- 21717716
TI  - [The Isidro Espinosa de los Reyes National Perinatology Institute].

PMID- 21717717
TI  - [Document of Aguascalientes].

PMID- 21717718
TI  - [Transplantation is still on the waiting list].

PMID- 21717719
TI  - [Validity and reliability of mammographic interpretation by Mexican radiologists,
      using the BI-RADS system].
AB  - OBJECTIVE: Mammographic interpretation using the BI-RADS system determines if a
      patient will continue in the regular screening program or needs additional
      studies for breast cancer diagnosis, hence the importance of its evaluation.
      Sensitivity, specificity, diagnostic accuracy of mammographic interpretation and
      inter- and intra-observer variation, were assessed in a random sample of 29
      radiologists from the Mexican Ministry of Health. MATERIAL AND METHODS: Eighty
      diagnostic and screening mammographic studies were selected from the National
      Cancer Institute in Mexico City. Under the same conditions, two interpretations
      using the BI-RADS system were performed by each of the participating
      radiologists. RESULTS: Sensitivity in the first and second measurement was 72 and
      74% respectively, while the specificity was 80% for the first and 82% for second.
      Multivariate analysis showed a positive association between the last year number
      of interpreted mammograms, the number of courses taken and diagnostic accuracy
      (beta=0.00002, 95% CI 0.000004, 0.00003, p=0.02, beta=0.005, CI 95% -0.0004,
      0.01, p=0.07, respectively). Inter-observer agreement was low in both
      measurements (kappa=0.24, kappa=0.25, respectively). However, after combining BI
      RADS categories in 2, agreement increased to 0.46 for both measurements. The
      intra-observer agreement was good (kappa=0.67). CONCLUSIONS: The number of
      mammographic studies interpreted the previous year is a good measure of the
      experience of the radiologist and is reflected in the diagnostic accuracy of
      mammographic interpretation. Courses on mammographic interpretation also have a
      positive impact on performance.

PMID- 21717720
TI  - [The pediatric patient at the end-of-life. A challenge for its identification and
      treatment. A survey in pediatricians and medical residents].
AB  - BACKGROUND: Identification of pediatric patients at the end-of-life is not easy
      because criteria used are based on adults' criteria. OBJECTIVES: In this survey
      we explore the children end-of-life definition pediatricians have, as well as to
      determine which interventions they use when caring a patient at end-of-life.
      MATERIAL AND METHODS:  SETTING: Tertiary referral pediatric hospital.
      PARTICIPANTS: Staff pediatricians (SP) and medical residents (MR). METHODS: A
      self-administrated questionnaire was built and validated. It contains five
      vignettes of pediatric patients: Two with WHO criteria for an end-of-life
      condition (EC) and three without an end-of-life condition (NEC). PARTICIPANTS
      identified each patient with or without an end-of-life condition, and which
      palliative actions they would perform accordingly Their responses were recorded
      in a 4-option Likert scale. Ordinal regression was used to assess if some of the
      participants' characteristics were related to the identification of an end-of
      life condition. RESULTS: Response rate was 84.2% (128/152); of whom 63 were SP
      and 65 MR. EC cases were well identified in 90 and 93%, while NEC in 30 and 40%,
      respectively Palliative actions were more according in EC patients, but around
      20% would not provide them. Among NEC patients, there were more disparities of
      palliative actions to be delivered, and it was statistically significantly.
      Ordinal regression showed that some participants' characteristics are associated
      to the appropriate identification of end-of-life patients; however, these factors
      were not consistent across the five scenarios. CONCLUSIONS: Among pediatricians,
      criteria of end-of-life conditions are not well established, neither the
      palliative actions. Educational interventions are needed to improve the quality
      of life of these children.

PMID- 21717721
TI  - [Trends of thyroid pathology in a referral center: steady prevalence of papillary
      thyroid carcinoma but goiter increase in thyroidectomies].
AB  - INTRODUCTION: Changes in the prevalence of papillary thyroid carcinoma (PTC) have
      been reported in institutions and national cancer registries. OBJECTIVE: To
      describe time trends in benign and malignant thyroid diseases in a national
      endocrine referral center. MATERIALS AND METHODS: Systematic review and
      classification of consecutive specimens with slides/paraffin blocks in surgical
      pathology archives (January 1990 to December 2009). Institutional registries,
      size, type of surgery and number of inclusion blocks were recorded. Patients
      whose registries were granted before January 1990 without nodules, but treated
      after twelve months for a suspicious thyroid lesion, were included. These
      patients in a passive follow-up permitted incidence density calculations. Cases
      were grouped by quinquennium. RESULTS: Institutional registers were conceded to
      103,961 persons worthy of attention, and 1,269 were submitted to thyroidectomies
      (1.2%). One hundred twenty four patients none treated for thyroid diseases before
      1990, developed thyroid nodules after 1991. The incidence density for goiter was
      0.05 person/year and for PTC 0.04 person/year in that group. In all series woman
      to man relation was 9:1 with a mean age of 45 years. Total or near total
      thyroidectomies were performed in 60% patients and benign diseases were diagnosed
      in 732 (52%) cases. Thyroid surgeries increased since 2005 (p=0.03) with a rise
      in goiter prevalence (0.25, 0.31, 0.35, 0.38, p for trend 0.0005), without
      significant increase in PTC prevalence (0.41, 0.43, 0.35, 0.40, p for trend 0.71)
      in thyroidectomies. CONCLUSIONS: Goiter as the only finding in thyroid specimens
      increased 52% in the last 20 years. PTC prevalence is steady with a higher number
      of tumors<3 cm.

PMID- 21717722
TI  - [Bone mineral density in patients with type 2 diabetes].
AB  - OBJECTIVE: To establish whether type 2 diabetes (T2D) is associated with changes
      in the bone mineral density (BMD) of femoral neck, total hip and lumbar spine.
      MATERIAL AND METHODS: Comparative cross-sectional study that included 450
      patients aged 30 years or more; 245 with, and 205 without T2D. Groups were
      matched by age. Degenerative joint disease, rheumatoid arthritis, neoplasia,
      renal failure, chronic liver disease, alcohol intake, prior treatment with drugs
      that modulate the BMD, Diabetes Mellitus Type 1 and other endocrinopathies were
      exclusion criteria. RESULTS: In the overall group, the presence of menopause was
      associated with osteoporosis in the hip (odds ratio -OR-4.2; CI95% 1.4-6.1),
      whereas T2D was a protective factor (OR 0.8; CI95% 0.4-0.9). Among premenopausal
      women, central obesity and total adiposity were associated with osteoporosis in
      the hip (OR 1.9; CI95% 1.1-3.9 and OR 2.1; CI95% 1.2-8.7) and femoral areas (OR
      2.1; CI95% 1.2-4.1 and OR 2.3; CI95% 1.3-7.1); T2D remained as protective factor
      (OR 0.7; CI95% 0.5-0.9 and OR 0.6; CI95% 0.4-0.9). The adjusted analysis by BMI,
      waist circumference, and total adiposity showed that T2D remained as a protective
      factor for osteoporosis in the hip (OR 0.8; CI95% 0.6-0.9) and femoral areas (OR
      0.7; CI95% 0.5-0.9). CONCLUSIONS: Our results suggest that T2D is an independent
      protective factor for osteoporosis.

PMID- 21717723
TI  - [A pharmacoepidemiological study of potential drug interactions and their
      determinant factors in hospitalized patients].
AB  - BACKGROUND: Prescription with more than one drug increases the risk of drug-drug
      interaction (D-DI), therapeutic failure, high pharmacological effect, or adverse
      events. The objectives of this study were to estimate the frequency of potential
      drug-drug interactions in prescriptions for hospitalized patients, and to
      identify the associated factors for these prescriptions. MATERIAL AND METHODS: A
      secondary data analysis ofa cohort was carried out, including 284 patients at the
      internal medicine ward in a third level hospital in Mexico City. Age, gender,
      diagnosis at admission, days of hospitalization, prescription and administration
      of the drugs were analyzed. The potential D-DI were identified and registered
      according to the severity. Descriptive and crude association analyses including
      the outcome variable and co variables, and Poisson regression analysis for
      adjusting the variables were performed. RESULTS: The median of age was 53+/-18
      years old; 53% of the patients were women, and 34% were older than 65 years of
      age. Sixty-three percent of the patients received one prescription identified as
      potential D-DI, and 33.5% of these prescriptions were "major D-DIs". The most
      frequently pairs of drugs prescribed were: fluoroquinolones-hypoglycemics
      (20.5%), enoxaparin- nonsteroidal antiinflammatory drugs or anticoagulants
      (18.1%), furosemide- angiotensin converting enzyme inhibitors (ACE inhibitor)
      (12.2%), alopurinol-ACE inhibitor (9%), and spironolactone-ACE inhibitor (9%).
      Thirty-three percent of patients older than 65 years of age received a
      prescription including one potential D-DI. Gender and the number of drugs
      received were associated factors to the potential D-DI. CONCLUSIONS: High
      percentage of prescriptions with potential D-DI makes necessary to implement
      educational programs or alert strategies including the identified associated
      factors, aimed to improve the quality of prescriptions and to reduce the risks
      for hospitalized patients.

PMID- 21717724
TI  - [Document of Aguascalientes. Exhibition of reasons. First Transplantation
      Bioethics Forum. Latin American and Caribbean Transplantation Society].

PMID- 21717725
TI  - [Long-term response to rituximab in a patient with acquired hemophilia].
AB  - A 28 year-old female without history of previous disease. In the seventh month of
      her first pregnancy she developed hemorrhagic tendency that worsened in the early
      postpartum period. Activated partial thromboplastin time was 110 sec
      (control=35.8 sec) with negative tests for lupus anticoagulant. Factor VIII was
      <1% and a factor VIII inhibitor titer was 84 Bethesda Units/mL (BU). Initial
      therapy included methylprednisolone, prednisone, and cyclophosphamide. After two
      weeks of treatment, clinical conditions of the patient improved slightly and she
      was discharged. Outpatient therapy included azathioprine, and prednisone for a
      period of 22 months but in-hospital management was several times required. We
      initiated rituximab 375 mg/m2/week/4 weeks. A clinical improvement and increased
      levels of factors VIII and XI were observed 10 weeks later and factor VIII
      inhibitor decreased to undetectable levels. After a 82-month follow-up period
      (since the first rituximab infusion), she is asymptomatic and factor VIII and
      factor XI plasma levels are 70% and 94%, respectively FVIII inhibitor level is
      still undetectable. Rituximab seems an alternative for the treatment of acquired
      hemophilia refractory to standard treatment.

PMID- 21717726
TI  - [Particle mass concentrations and size distribution during and after the Beijing
      Olympic Games].
AB  - To study the variance characteristics of particle mass and number concentration
      during and after the Beijing Olympic Games, on-line measurements of particle mass
      and number concentration were conducted on the rooftop of a two-story building
      near the 325 m meteorological observation tower in the courtyard of the Institute
      of Atmospheric Physics during 2008-08-08 - 2008- 10-07 by using TEOM and APS.
      Sources and transportation of atmospheric particles during the experiment were
      discussed with surface meteorology data and backward trajectories calculated
      using HYSPLIT model. It had been found that the average mass concentration of
      PM2.5-10 and PM2.5 were (23.1 +/- 1.6) microg x m(-3) and (55.5 +/- 7.3) microg x
      m(-3) during the Olympic time, which were 18.2% and 16.0% lower than non-Olympic
      time, and 22.3% and 18.0% lower than non-Source control time. In Olympic time,
      average number concentration of PN2.5-10 and PN0.5-2.5 were (15 +/- 1) cm(-3) and
      (3138 +/- 567) cm(-3), which were 23.4% and 27.5% lower than non-Olympic time,
      and 29.5% and 34.3% lower than non-Source control time. According to the
      correlation analysis result of particle matter and meteorological factors, there
      were significant linear relationships between wind speed, relative humidity and
      precipitation of prior day and particle mass and number concentrations, stepwise
      regression analysis showed that 42% and 53% of the variance in mass and number
      concentration of fine particle were both accounted for wind speed and relative
      humility, while 21% and 39% of the variance in mass and number concentration of
      coarse particle were both accounted for wind speed and precipitation of prior
      day. For the entire period, 46% of total air masses came from regions south of
      Beijing like Baoding and Shijiazhuang and were favor to increase both the mass
      and number concentration of fine particles, whereas air masses transported from
      the north and near north regions had a great effect on scavenging both fine and
      coarse particles in Beijing, indicating coarse particles mostly came from local
      sources and fine particles mainly influenced by regional transport in Beijing.
      According to the comparative analysis result of two accumulation- diffusion
      processes, meteorological factors were only the causes of particle mass and
      number fluctuations, while the significant decrease of coarse and fine particles
      concentrations were mainly contributed to weaker emission of particles from local
      sources and weaker transport from regional area around Beijing, suggesting
      synchronous emission abatement of six provinces and cities of North China is the
      main factor that ensured the excellent air quality during the Olympic Games.

PMID- 21717727
TI  - [Comparison of ozone between Beijing and downstream area].
AB  - In this study ozone and meteorological factors were measured at an urban station
      and a downwind rural station around Beijing from June 2005 to September 2006. The
      ozone at urban station exhibited stronger diurnal and seasonal variations than
      that at the rural station. The maximum concentrations of ozone were 198.9 x 10(
      9) and 151.2 x 10(-9) at Beijing and Xinglong, while there were 171 hours and 255
      hours in which ozone exceeded the China's norm, respectively. 90% of the
      exceeding occurrences happened before 16:00 in Beijing, while more than 82%
      happened at night in Xinglong. The peak concentration of ozone at Xinglong in the
      diurnal cycle was 3-4 hours lag of that at Beijing because of the influence of
      air mass from Beijing. Double ozone peaks phenomena can be found at Xinglong due
      to the mountain-valley breezes especially in the summertime. Stagnant
      meteorological conditions and mountain-valley breezes can cause ozone
      accumulation at downwind areas. The AOT40 values were 23.1 x 10(-6) x h, 26.5 x
      10(-6) x h, and 14.1 x 10(-6) x h in spring, summer and autumn respectively at
      Xinglong, which could cause more than 30% lose in wheat yields.

PMID- 21717728
TI  - [Atmospheric nucleation rate at Xinken site in the Pearl River Delta of China].
AB  - The atmospheric nucleation rates are calculated, the nucleation mechanism and
      factors affecting the calculation are investigated at Xinken Site in the Pearl
      River Delta of China. Based on particle size distribution data from Xinken site
      during PRIDE-PRD2004, the apparent formation rates of 3 nm particles are
      obtained. Nucleation rates for critical nuclei of 1 nm size are analyzed from
      particle flux equation of different size in the diameter axis. The results show
      the 3 nm apparent formation rates during the new particle formation events are
      7.2-9.4 cm(-3) x s(-1), the atmospheric nucleation rate for 1 nm critical nuclei
      are 7.65 x 10(2)-1.14 x 10(5) cm(-3). The derived nucleation rates are consistent
      with the concentrations of precursor vapor sulphuric acid, which are supposed to
      participate nucleation in most cases. With higher contribution of accumulation
      mode background aerosol to coagulation sink, the variation in particle number
      during event period imposes neglectable influence on the calculated nucleation
      rates. Information on nucleation rates provide further insight into the
      nucleation mechanism. Since variation in critical nuclei size may lead large
      uncertainty to nucleation rates, identification of the exact critical nuclei size
      is important for nucleation rate study.

PMID- 21717729
TI  - [VOCs analyzing and odor indicator selecting in ambient air of landfill area].
AB  - The odor pollution of landfill is one of seriously pollutions in city ambient
      area. Main pollution points in the landfill area have been detected by
      preliminary research. For a particular purpose to recover the materials changing
      in odor dispersion process and to find out odor indication material, GC-MS method
      was used to detect materials in the different site at down wind direction. Then,
      similarity coefficient of VOCs (volatile organic compounds) composition between
      every two site were calculated and compared to look for changing regular of odor
      pollution in diffusion process. The odor pollution indictor material has be found
      in the materials that appeared in down wind direction of operation area and
      compared its' olfaction threshold. The results show that: there have 19 types of
      common materials in the landfill area, including monoaromatics, alkanes and
      halogenated compounds; Materials in the air of operation area site has marked
      influence on down windward direction air of landfill, and m-xlyene has been
      selected as odor pollution indictor of landfill air by this research.

PMID- 21717730
TI  - [Nitrogen concentrations and stable isotope in epilithic mosses to investigate
      atmospheric N deposition and N sources in Jiangxi Province].
AB  - Atmospheric N deposition and N sources in Jiangxi Province were investigated on
      the basis of the nitrogen concentrations and nitrogen isotope in epilithic mosses
      which collected from 11 cities of the province during 2009-2010. Mean nitrogen
      concentrations ranged from 2.46% to 3.48% and showed a significant regional
      difference. The highest was found in the northwestern of the province and the
      lowest in the southeastern, reflecting that the level of the atmospheric N
      deposition gradually decreased from the north to the south in the province. The
      higher N concentrations in urban mosses than in suburban mosses indicated that
      the urban areas received higher rates of nitrogen deposition than suburbs areas.
      Mosses 15N values varied from (-9.74 +/- 0.25) per thousand to (-1.96 +/- 1.30)
      per thousand. More negative delta15N values of urban mosses (-5.51 per thousand
      9.74 per thousand) indicated that more NH3 was released from excretory wastes and
      sewage, while less negative delta15N values of suburban mosses (-4.81 per
      thousand-1.96 per thousand) suggested an important contribution from agricultural
      NH3 emission due to intensive fertilizer application. This research provides
      basic information for further study on the ecological and environmental effects
      of atmospheric N deposition.

PMID- 21717731
TI  - [Experimental research of purification NO-containing gas by aqueous oxidation
      with UV/H2O2].
AB  - The influence of some experimental factors on removal efficiency of nitric oxide
      (NO) under the condition of liquid-phase oxidation with UV/H2O2, such as H2O2
      concentration, solution temperature, initial pH, NO concentration, illumination
      condition, O2 content and gas flow rate, were investigated by employing
      orthogonal experiments and single factor experiments. The results showed that NO
      could be efficiently removed by the aqueous oxidation technology with UV/H2O2
      system, and the highest NO removal rate was about 80%. Moreover, H2O2
      concentration, temperature and initial pH had varying degree effects on purifying
      NO-containing gas, whereas NO removal rate were more affected by H2O2
      concentration and temperature. The single factor experimental results showed that
      high NO removal rate could be obtained when H2O2 concentration was 0.2 mol/L and
      the initial pH was 6-7. H2O2 concentration and initial pH should be maintained at
      an appropriate level or the production of *OH could be restricted, which would
      result in lower NO removal rate. The optimum operation temperature was 40 degrees
      C, which is lower than common operating temperature (50 degrees) for the wet
      scrubber. Enlarging the illumination strength and O2 content could improve the NO
      removal rate. Furthermore, the NO removal rate was also controlled by the area
      and coefficient of gas-liquid mass transfer.

PMID- 21717732
TI  - [Relationship between groundwater quality index of nutrition element and organic
      matter in riparian zone and water quality in river].
AB  - Riparian zone hydrology is dominated by shallow groundwater with complex
      interactions between groundwater and surface water. There are obvious relations
      of discharge and recharge between groundwater and surface water. Flood is an
      important hydrological incident that affects groundwater quality in riparian
      zone. By observing variations of physical and chemical groundwater indicators in
      riparian zone at the Kouma section of the Yellow River Wetland, especially those
      took place in the period of regulation for water and sediment at the Xiaolangdi
      Reservoir, relationship between the groundwater quality in riparian zone and the
      flood water quality in the river is studied. Results show that there will be
      great risk of nitrogen, phosphorus, nitrate nitrogen and organic matter
      permeating into the groundwater if floodplain changes into farmland. As the
      special control unit of nitrogen pollution between rivers and artificial
      wetlands, dry fanning areas near the river play a very important role in nitrogen
      migration between river and groundwater. Farm manure as base fertilizer may he an
      important source of phosphorus leak and loss at the artificial wetlands.
      Phosphorus leaks into the groundwater and is transferred along the hydraulic
      gradient, especially during the period of regulation for water and sediment at
      the Xiaolangdi Reservoir. The land use types and farming systems of the riparian
      floodplain have a major impact on the nitrate nitrogen contents of the
      groundwater. Nitrogen can infiltrate and accumulate quickly at anaerobic
      conditions in the fish pond area, and the annual nitrogen achieves a relatively
      balanced state in lotus area. In those areas, the soil is flooded and at
      anaerobic condition in spring and summer, nitrogen infiltrates and
      denitrification significantly, but soil is not flooded and at aerobic condition
      in the autumn and winter, and during these time, a significant nitrogen
      nitrification process occurs. In the area between 50 m and 200 m from the river
      bank, which is the efficient microbial nitrogen purification unit, nitrification
      denitrification is intensive. Farm manure is an important source of organic
      matter loss at the artificial wetlands. Floodplain has sandy soil texture, with
      high infiltration capacity and low water and fertilizer conservation ability.
      Such features are prone for the loss of surface soil nutrition and organic matter
      if agricultural activities taken place in these areas change the land use of
      wetlands and apply extensive fertilizer. The infiltrated nutrition elements and
      organic matter can pollute the groundwater and the river. Compared with the
      losses of nutrition element and organic matter caused by surface runoff, the
      infiltrated process is even more prominent. As typical floodplain groundwater
      river ecotone, the area between 50 m and 200 m from the river bank is a momentous
      pollution purification unit. Rational protection for this region is critical for
      the conservation of water quality in the river and groundwater.

PMID- 21717733
TI  - [Characteristics of constant inorganic ions in precipitation at different
      altitudes precipitation in Yulong Snow Mountain area].
AB  - According to the different altitudes precipitation samples in Yulong Snow
      Mountain area in Yunnan Province from July 26 2005 to July 31 2005, the
      precipitation chemical characteristics of different altitudes were analyzed with
      the sea salt iron tracer analysis method. Sea salt tracer analysis showed that Cl
      , Na+ had high proportion marine source, amounting 74.79% and 73.53% respectively
      while the other ions mainly were nonmarine sources. The average percentage of
      nonmarine sources of NO3-, SO4(2-), K+, Mg2+, Ca2+ were 100%, 93.54%, 97.29%,
      81.77%, 99.66%. Statistics chart showed the changes of cation outweigh the anion
      greatly. The cation concentration ranged between 0.51-5.26 mg/L and anion
      concentration ranged between 0.99-4.90 mg/L, inferring the cation have more
      complicated sources. Further analysis showed terrestrial ions, especially near
      source terrestrial ion composition greatly impact the precipitation ion
      concentration. Human activities lead to higher anion concentration at alt. 2950
      4800 m and precipitation ion concentration was correlated significantly with
      local atmospheric circulation. The most rock are limestone caused high
      precipitation cations in Yulong Snow Mountain, such as Ca2+ and Mg2+.

PMID- 21717734
TI  - [Regional characteristics of ion concentration in glacial snowpits over the
      Tibetan Plateau and source analysis].
AB  - The characteristics of ion concentration were studied in snowpit samples
      collected from the GRHK glacier, the XDKMD glacier and the YZF glacier over the
      Tibetan Plateau. Samples of snowpits in these three glaciers were analyzed by ion
      chromatography and ion sources were also explored by correlation analysis. The
      results indicated that the concentration of Ca2+, Mg2+, Na+, Cl- and SO4(2-)
      increased from the GRHK glacier to the XDKMD glacier and to the YZF glacier,
      suggesting that the terrestrial matter were major origin from the south to north
      over the Tibetan Plateau. The concentration of Cl-, Na+ and SO4(2-) in YZF
      glacier was higher by many times than GRHK glacier and XDKMD glacier, Perhaps
      mainly come from the evaporation of salt lake and the weather of mineral salts in
      the Qaidam Basin. The sources of NO3-, K+ and NH4+; were complicated and it is
      not obvious for the indication of environment.

PMID- 21717735
TI  - [Seasonal variation of chlorophyll a and its potential relationship with various
      algal species in Xiaojiang River backwater area, Three Gorges Reservoir].
AB  - The seasonal variation of Chlorophyll a (Chla) in Xiaojiang river backwater area
      from May 2007 to April 2008 with 115 water samples was studied. Three trophic
      states i.e. Chla < or = 5 microg x L(-1), 5 microg x L(-1) < Chla < or = 19
      microg x L(-1) and Chla >19 microg x L(-1), were applied to represent the
      potential relationship of Chla, algal cell density (CellD) and biomass (BioM) in
      Xiaojiang river backwater area. The results showed that the algal cell density,
      biomass and Chla had significantly positive correlations (r > 0.70, Sig. < or =
      0.01) and their seasonal variation processes are synchronous. The average values
      of Chla and biomass of chlorophyta, diatoms, cyanobacteria, dinoflagellate during
      the study period in Xiaojiang river backwater area were (9.58 +/- 10.77), (1605
      +/- 647), (707 +/- 124), (511 +/- 266) and (4019 +/- 1345) microg x L(-1),
      respectively. When Chla < or = 5 microg x L(-1), chlorophyta, diatoms and Chla
      were significantly positively correlated; while under 5 microg x L(-1) < Chla <
      or = 19 microg x L(-1) level, only cyanophytes and Chla showed a significantly
      positive correlation; At Chla > 19 microg x L(-1) level, Chla was positively
      correlated to dinoflagellate, and there were no significant correlations among
      Chla and other algae.

PMID- 21717736
TI  - [Characteristics of macrozoobenthic assemblages and their relationship with
      aquatic environmental factors in streams of Lake Dianchi watershed in the wet
      season].
AB  - The characteristics of macrozoobenthic assemblages and their relationship with
      aquatic environmental factors in the 29 streams of the Lake Dianchi (LD)
      watershed in the wet season were studied. Biosurveys of macrozoobenthic
      assemblages during July and August 2009, as well as 17 mensal aquatic
      physicochemical parameters from September 2008 to August 2009 were carried out at
      29 sampling sites. The objectives were to demonstrate the characteristics of
      macrozoobenthic assemblages in streams of the LD watershed in the wet season, to
      identify the key aquatic environmental factors affecting these assemblages, and
      to investigate the relationship of spatial patterns between the Shannon-Weaver
      diversity index of the assemblages and the assessment of aquatic environmental
      quality. Results identified 3 divisions, 7 families, and 8 genera of
      macrozoobenthos, including 4 families and 5 genera of Annelida, 2 families and 2
      genera of Mollusca, and 1 family and 1 genus of Arthropoda. Among these,
      Limnodrilus (Annelida) , a tolerant species, was the dominant genus. TN, NH4(+)
      N, TP, and DO were the key aquatic environmental factors affecting the
      macrozoobenthic assemblages, respectively 2.03-32.00, 0.34-26.66, 0.09-3.20, and
      0.10-6.80 mg/L. The spatial patterns of the Shannon-Weaver diversity index of
      macrozoobenthic assemblages and the assessments of aquatic environmental quality
      were both greatest in the streams flowing into the east LD (Luolonghe, Laoyuhe,
      and Nanchonghe rivers), followed by those flowing into the south LD (Yunihe,
      Laochaihe, Baiyuhe, Cixianghe, Dongdahe, Zhonghe and Guchenghe rivers), and least
      in those flowing into the north LD (Wangjiaduiqu, Xinyunlianghe, Laoyunlianghe,
      Wulonghe, Daguanhe, Xibahe, Chuanfanghe, Cailianhe, Jinjiahe, Panlongjiang,
      Daqinghe, Haihe, Liujiabaoxianghe, Xiaoqinghe, Wujiabaoxianghe, Xiabahe,
      Laobaoxianghe, Xinbaoxianghe, and Maliaohe rivers).

PMID- 21717737
TI  - [Evaluation and ecological control of the eutrophic state of Gudong reservoir].
AB  - The eutrophic state of Gudong reservoir and relative factors were investigated
      and evaluated. Then a comprehensive ecological control technology was proposed.
      The amount of herbivorous fish and filter-feeding fish was determined both
      through theoretic calculation and experimental test. The results demonstrated
      that Potamogeton crispus was the dominant grass over 80%, the phytoplankton
      biomass was 22.32 mg/L, and the total phosphors was 0.310 g/(m2 x a), which
      suggested that Gudong reservoir was on the eutrophic state. Through ecological
      engineering by controlling the biomass of Hypophthalmichthys molitrix and
      Aristichthys nobilis at 19-25 g/m3, the algae biomass was reduced from 14.6 mg/L
      to 3 mg/L at September, the annual average total phosphorous, nitrogen and
      permanganate index were reduced from 0.06 mg/L, 3.06 mg/L and 4.42 mg/L to 0.03
      mg/L, 1.58 mg/L and 3.73 mg/L, respectively, which showed that the reservoir
      water quality has been obviously improved. Also, the flocculant dosage to treat
      this reservoir water was reduced from 42 g/m3 to 25 g/m3 after ecologic control.
      The results showed that the eutrophication could be controlled effectively by
      adopting the ecological restoration technology with rationally introducing the
      herbivorous fish and filter-feeding fish, and significant benefits can also be
      achieved.

PMID- 21717738
TI  - [Study on the nitrogen and phosphorus uptake ability of four plants cultivated on
      floating-bed].
AB  - Plant floating-bed tested engineering was constructed for eutrophication control
      in Dian-shan Lake, the characteristics and nutrient uptake abilities of Canna
      indica, Iris pseudacorus, Thalia dealbata and Lythrum salicaria were compared. It
      shows that using upper and lower nylon nets to fix the plants on the floating-bed
      is beneficial for them to grow and reproduce rapidly. Survival rates of Canna
      indica, lris pseudacorus, Thalia dealbata and Lythrum salicaria are 83.33%,
      83.33%, 76.67% and 53.33% respectively. Ramets of Canna indica and Thalia
      dealbata are 64 and 78 respectively in November, and the biomass (fresh weight)
      of these two plants are 32.0 and 38.6 kg per individual plant. Nitrogen (N) and
      phosphorus (P) content in stems/leaves of Canna indica and Thalia dealbata are
      greater than those in roots. The ratio between stems/leaves and roots of N, P
      content in Canna indica are 1.40 and 1.21 respectively, while 1.59 and 1.08 in
      Thalia dealbata. The difference of cumulative N, P content in plants is mostly on
      account of different plant biomass. N uptake ability of Thalia dealbata is the
      highest, which is 457.11 g per square; Canna indica has the highest P uptake
      ability, which is 41.29 g per square. N, P uptake ability of stems/leaves in
      Canna indica are 2.17 and 1.86 times higher than that of roots, while 1.73 and
      1.17 times higher respectively in Thalia dealbata. Thus, Canna indica and Thalia
      dealbata are recommended as the floating-bed plants to control the eutrophication
      in Dian-shan Lake.

PMID- 21717739
TI  - [Characteristics of organic phosphorus fractions in different trophic sediments
      of lakes, China].
AB  - In this study, the characteristics of organic phosphorus fractions in sediments
      of seven lakes with different drainage basin feature, ecological structure, and
      polluted levels from different regions were investigated, and the relationships
      between organic phosphorus (Po), inorganic phosphorus (Pi) and bioavailable
      characters were also discussed. The difference of the related content of Po in
      different sediments indicated the discrepancy of phosphorus sources and
      biogeochemical cycles in different lakes. Organic matter (OM) was significantly
      correlated with Po (R2 = 0.80, p < 0.01), and except for Lake Qilu, OM was
      significantly correlated with labile Po, moderately labile Po and nonlabile Po in
      all studied sediments (R2 were 0.85, 0.52, 0.80 respectively, p < 0.01). The
      moderately labile Po and nonlabile Po were the main fraction of Po in all studied
      lakes, and the relative contributions to total Po were 15.12%-66.73% and 27.99%
      77.72%, respectively. The mean proportion of labile Po was 6.1% in studied
      sediments. The rank order of Po fractions was residual Po > HCl-Po > fulvic acid
      Po > humic acid-Po > NaHCO3-Po with mean relative proportion 8.3:3.1:2.2:1.8:1.0.
      Labile Po was significantly correlated with total phosphorus (TP), Pi , Po,
      NaHCO3-Pi and NaOH-Pi . Furthermore, Labile Po was also significantly correlated
      with T), Po and NaOH-Pi in all studied sediments, which suggested that labile Po
      was transformed into bioavailable phosphorus and the nonlabile Po may become a
      potential source of available phosphorus, although it was considered as highly
      resistant fraction.

PMID- 21717740
TI  - [Organic phosphorus mineralization in the sediments under the impact of pH and
      temperature].
AB  - In the simulation, Bowman-Cole modified organic phosphorus fractionation system
      was used for the analysis of pH and temperature impact on organic phosphorus
      mineralization. The results showed that when pH were 6.5, 7.5 and 8.5, organic
      phosphorus (TOP) accounted for 31.71%-41.73%, 30.85%-43.29% and 27.25%-56.31% of
      total phosphorus (TP) in the sediments respectively. Alkalescent environment
      accelerated the process of organic phosphorus mineralization which slowed down
      when environment was neutral. When temperatures were 15 degrees C, 25 degrees C
      and 35 degrees C, TOP accounted for 29.07%-46. 62%, 27.81%-46.62% and 34.56%
      46.62% of TP respectively. The process of organic phosphorus mineralization
      increased with temperature in the first 10 days but decreased in the following 20
      days. Under acidic and high temperature environment, labile organic phosphorus
      (LOP) has a strong influence on the water quality because of the simultaneous
      processes of transformations from nonlabile organic phosphorus (NOP) to
      moderately labile organic phosphorus (MLOP) and from MLOP to LOP.

PMID- 21717741
TI  - [Performance of phosphorus removal by simulated riparian zone enhanced with red
      mud treating reclaimed water].
AB  - The effect of red mud and the role of plants on the phosphorus removal of the
      reclaimed water were studied by lab-scale simulated riparian zone, which made
      well use of sintered red mud with well adsorption capacity for phosphorous due to
      its high contents of Ca, Al and Fe oxides. The results show that the suitable
      ratio range of adding red mud is 2.5%-5.0%, and correspondingly, the removal of
      phosphorus is as high as 82%-76%, resulting in 0.22-0. 29 mg/L of effluent TP
      concentration and 74%-75% of SRP/TP. When the percentage of adding red mud is
      2.5%, comparing with the system without plants, the performance of the system
      with plants improves by 4%, reaching to 86% and 0. 17 mg/L of effluent TP
      concentration. Obviously, red mud can be directly used in the riparian zone to
      enhance the phosphorus removal as a new and cheap material.

PMID- 21717742
TI  - [Optimization and stability of denitrifying-phosphorus removal in a two-sludge
      system for treating wastewater with low carbon source].
AB  - Poly-beta-hydroxybutyrate (PHB) could be efficiently accumulated under optimized
      conditions in a sequencing batch moving bed biological reactor (SBMBBR), and a
      high performance of denitrifying phosphorus removal in the reactor could be
      achieved by coupling with a two-sludge system. Denitrifying phosphorus removal
      achieved the highest efficiency under influent COD of 200 mg/L, neutral pH and
      stirring speed of 80 r/min. The removal rates of phosphorus, NO3(-)-N and NO2(-)
      N reached 83.7%, 81.4% and above 100%, respectively. High biomass in the SBMBBR
      is one of keys to improve the performance in removal of nitrogen and phosphorus.
      When the SBMBBR was conducted under a two-sludge system, stable and high
      performance was obtained. Removal rates of phosphorus and TN reached 89.2% and
      84.5% under the influent COD of 140-170 mg/L and TN of 34-42 mg/L, respectively.
      In the process, phosphorus content in excess sludge approached to that in the
      feeding, and other path of phosphorus removal was not found.

PMID- 21717743
TI  - [Determination of kinetic parameters of activated sludge in an MBR wastewater
      treatment plant].
AB  - One of the main problems in application of MBR technology is lack of reliable
      kinetic parameters for process design. The activated sludge in the aerobic tank
      of an MBR municipal wastewater treatment plant was investigated therefore. Using
      oxygen utilization rate method, following kinetic parameters were measured:
      heterotrophic yield coefficient YH = 0.693, autotrophic yield coefficient Y(A) =
      0.263, heterotrophic decay coefficient KdH, = 0.108 d(-1), autotrophic yield
      coefficient KdA = 0.089 d(-1), specific maximum COD removal rate v(mS), = 1.94 mg
      x (mg x d)(-1), half saturation constant for COD removal K(S) = 34.6 mg x L(-1),
      specific maximum ammonia removal rate vmN = 0.18 mg x (mg x d)(-1), half
      saturation constant for ammonia removal K(N) = 1.06 mg x L(-1). Compared with the
      normal reported data of conventional activated sludge process (CAS), Y(H), KdH
      obtained are higher and vmS, vmN are lower. The high sludge concentration
      condition of MBR process may account for those differences.

PMID- 21717744
TI  - [Enriched experiment and endogenous processes of glycogen-accumulating organisms
      (GAOs)].
AB  - Cell decay is an important part of microbiological endogenous processes, which
      consists of cell death (reduction in the amount of active bacteria) and activity
      decay (reduction in the specific activity of active bacteria). By means of
      measuring maximal anaerobic volatile fatty acid (VFA) uptake rates (VFAUR),
      analyzing 16S rRNA with fluorescence in-situ hybridization (FISH) and observing
      membrane integrity by live/dead staining, the aerobic decay characteristics of
      glycogen-accumulating organisms (GAOs) in an enriched GAOs sequencing batch
      reactor (SBR) system were investigated. It was experimentally identified that a
      highly enriched culture of GAOs (94%) was obtained by maintaining the temperature
      at 30 degrees C in the SBR and a high m (COD): m (P) at 100 in the feed. The
      experimental results and calculations revealed that the decay and death rates of
      GAOs were 0.132 d(-1) and 0.034 d(-1) respectively, which demonstrated that cell
      death and activity decay accounted for respective 26% and 74% of the total GAOs
      cell decay. For this reason, cell death was only a minor factor causing the cell
      decay of GAOs, and activity decay was mostly responsible for this process.

PMID- 21717745
TI  - [Harvest of the carbon source in wastewater by the adsorption and desorption of
      activated sludge].
AB  - The carbon source in municipal wastewater was adsorbed by activated sludge and
      then harvested through the hydrolysis of activated sludge. Results indicated that
      activated sludge had high absorbing ability towards organic carbon and phosphorus
      under continuous operation mode, and the average COD and TP absorption rate
      reached as high as 63% and 76%, respectively. Moreover, about 50% of the soluble
      carbon source was outside of the sludge cell and could be released under mild
      hydrolysis condition. Whereas the absorbed amount of nitrogen was relatively low,
      and the removal rate of ammonia was only 13% . Furthermore, the releases of
      organic carbon, nitrogen and phosphorus from the sludge absorbing pollutants in
      the wastewater were studied. By comparing different hydrolysis conditions of
      normal (pH 7.5, 20 degrees C), heating (pH 7.5, 60 degrees C) and the alkaline
      heating (pH 11, 60 degrees C), the last one presented the optimum hydrolysis
      efficiency. Under which, the release rate of COD could reach 320 mg/g after 24
      hours, whereas nitrogen and phosphorus just obtained low release rates of 18 mg/g
      and 2 mg/g, respectively. Results indicate that the carbon source in wastewater
      could be harvested by the adsorption and desorption of activated sludge, and the
      concentrations of nitrogen and phosphorus are low and would not influence the
      reuse of the harvested carbon source.

PMID- 21717746
TI  - [Analysis of novel style biological fluidized bed A/O combined process in dyeing
      wastewater treatment].
AB  - A novel biological fluidized bed was designed and developed to deal with high
      concentration refractory organic industrial wastewater. From 12 successful
      projects, three cases of dyeing wastewater treatment projects with the scale of
      1200, 2000 and 13000 m3/d respectively were selected to analyze the principle of
      treating refractory organic wastewater with fluidized bed technology and discuss
      the superiority of self-developed biological fluidized bed from the aspects of
      technical and economic feasibility. In the three cases, when the hydraulic
      retention time (HRT) of biological system were 23, 34 and 21. 8 h, and the volume
      loading of influents (COD) were 1.75, 4.75 and 2.97 kg/(m3 x d), the
      corresponding COD removal were 97.3%, 98.1% and 95.8%. Furthermore the operating
      costs of projects were 0.91, 1.17 and 0.88 yuan per ton of water respectively.
      The index of effluent all met the 1st grade of Guangdong Province wastewater
      discharge standard. Results showed that the biological fluidized bed had
      characteristics of shorter retention time, greater oxygen utilization rate,
      faster conversion rate of organic pollutants and less sludge production, which
      made it overcome the shortcomings of traditional methods in printing and dyeing
      wastewater treatment. Considering the development of technology and the
      combination of ecological security and recycling resources, a low-carbon
      wastewater treatment process was proposed.

PMID- 21717747
TI  - [Wastewater from the condensation and drying section of ABS was pretreated by
      microelectrolysis].
AB  - Wastewater from the condensation and drying section of acrylonitrile-butadiene
      styrene (ABS) resin plant was pretreated by the microelectrolysis, and the effect
      of the influent pH value on the pollution removal efficiency of the
      microelectrolysis was mainly studied. In order to study the electrochemical
      action of the microelectrolysis for the degradation of toxic refractory organic
      pollutants, two control experiments of activated carbon and iron were set up. The
      results showed that the TOC removal efficiencies were all fluctuated between 40%
      and 60% under the condition of different influent pH values. The
      microelectrolysis can decompose and transform the toxic refractory organic
      pollutants and increase the BOD5/COD ratio from 0.32 to 0.60, which increased the
      biodegradability of ABS resin wastewater significantly. When the pH value of
      influent was 4.0, the BOD5/COD ratio of effluent reached 0.71. The result of UV
      vis spectra indicates that the removal efficiency of the organic nitrile was the
      highest with influent pH was 4.0. Therefore, the best influent pH value of
      microelectrolysis was 4.0.

PMID- 21717748
TI  - [Catalyst effect and the structure-activity characteristics of redox mediators on
      the reactive brilliant red K-2BP decolorization].
AB  - Four selected quinone redox mediators with similar structure were conducted to
      accelerate reactive brilliant red K-2BP decolorization, and the accelerating
      structure-activity of redox mediators on the decolorization was also studied.
      Batch experiments were carried out to determine the catalyst effect on the
      decolorization of reactive brilliant red K-2BP with temperature of 35 degrees C
      and under anaerobic conditions. The experiment results suggested that (1) four
      similar chemical structure redox mediators [1, 4, 5, 8-Tetrachloroanthraquinone
      (1,4,5,8-AQ), Anthraquinone (AQ), 1,8-Dichloroanthraquinone (1,8-AQ), 1,5
      Dichloroanthraquinone (1,5-AQ)], all accelerated the decolorization rate of
      reactive brilliant red K-2BP and the reaction rate was enhanced 1.4-3 times; (2)
      the accelerating order was 1,8-AQ >1 ,5-AQ > AQ >1,4,5,8-AQ at the quinone
      mediator concentration of 4 mmol x L(-1) and reactive brilliant red K-2BP
      concentration of 300 mg x L(-1); (3) under the reactive brilliant red K-2BP
      concentration of 300 mg x L(-1), 1,8-AQ had best accelerating effect, and the
      relationship between decoloring rate constants and 1,8-AQ concentration; (4) and
      the mediator acclerating effects also related to substituent positioning effects
      and conjugated effects. The structure-activity mathematical model of redox
      mediators was put forward, which could improve water-insoluble redox mediators
      catalytic strengthening theory system.

PMID- 21717749
TI  - [Matching study on treatment of sewage from highway service area by ecological
      soil system in Chongqing].
AB  - The osmotic coefficient by clear water and sewage, static adsorption, dynamic and
      water penetration tests were conducted to determine the parameters, which
      including materials matching, hydraulic loading, and wet to dry ratio, in the
      treatment of sewage from highway service area (SHSA) in Chongqing by ecological
      soil system. The results showed that, according to principles of easier getting,
      high and stable hydraulic load, large decontamination capability, the materials
      matching of working layer SHSA was made of 30.67% soil, 61.33% sand and 8.00%
      cinder in Chongqing, and the supporting layer was consisted of 0.20 m cable and
      0.10 m broken stone (height). The total height of the ecological soil system was
      1.6 m, at which 1.00, 1.20, 1.40, 1.60 m department of hydraulic loading were
      0.344, 0.322, 0.307, 0.298 m x d(-1), respectively. The flooding period of
      working layer was 1 d and the drying period 1.5 d, i. e, the ratio of wet to dry
      was 1:1.5.

PMID- 21717750
TI  - [Estimation of perfluorinated compounds emissions from major rivers and
      wastewater treatment plants in China].
AB  - In order to estimate the environmental emissions of perfluorinated compounds
      (PFCs), mass calculation method and monitoring data available were used to
      estimate the mass discharges of PFCs from some major rivers and several
      wastewater treatment plants (WWTP) in several cities in China. Total river mass
      discharges of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA)
      in main rivers from coastal regions of the North Bohai Sea (NBS)were 122 kg/a and
      216 kg/a, respectively, and the Daliao River and Dalin River contributed mostly
      to the total discharge of PFOS and PFOA in this area. Highest level of PFOS
      discharges were found in the Pearl River Delta and Yangze River, which were 4.47
      x 10(3) kg/a and 807 kg/a respectively. The highest level of PFOA discharges were
      found in Yangze River and Huangpu River, which were 3.92 x 10(4) kg/a and 1.60 x
      10(4) kg/a respectively. The per capita discharge of PFOS from WWTP in Beijing
      and Tianjin were 291 microg/(a x person) and 221 microg/(a x person),
      respectively, much less than the average per capita discharge of PFOS from WWTP
      in Switzerland and the USA. Relatively greater sewage sludge PFCs emissions were
      concentrated in industrialized cities where PFCs related industries were located.
      The results can be used for the identification of sources and emission control of
      PFCs in the future.

PMID- 21717751
TI  - [Contamination of polycyclic aromatic hydrocarbons in surface water in
      underground river of Dashiwei Tiankeng group in karst area, Guangxi].
AB  - In order to understand the composition, sources and contamination characteristics
      of PAHs in water from underground river of Dashiwei Tiankeng group in typical
      karst area located in Leye County, Guangxi. The water samples were collected from
      different sections to analyze 16 priority polycyclic aromatic hydrocarbons using
      GC-MS. The results showed that concentration of Sigma PAHs (the total PAHs) in
      water ranges from 54.7 ng/L to 192.0 ng/L, with an average concentration of 102.3
      ng/L. The predominant PAHs in water are 2-3 ring PAHs, accounting for 65.1% of
      PAHs. The distribution of PAHs in water sampled along the underground river
      indicates that the mean concentration of PAHs in upstream area is higher than
      that of downstream because of wastewater discharge. Meanwhile, the underground
      river has some adsorption effect to 4-6 ring PAHs. The concentration of Sigma
      PAHs at Dashiwei Tiankeng section increases 93.8% attribute to the release of
      PAHs coming from Karst environmental medium and/or atmospheric transmission in
      underground river system. However, the concentration of Sigma PAHs at the
      confluence section of the tributary of Dashiwei Tiankeng is 47.3% less than that
      of the first upstream section duo to dilution. The concentration of Sigma PAHs at
      Bailang outlet section is 128.3% and 17.8% higher than that of flow-in section
      and Dashiwei Tiankeng section respectively. The ratios of specific PAHs indicate
      that the PAH sources in Leye County and Dashiwei Tiankeng areas mainly come from
      both petroleum and its combustion. However, the petroleum origin comes from
      anthropogenic inputs in town and the natural inputs in Dashiwei Tiankeng. The PAH
      sources in rural areas are mainly originating from the combustion of grass, wood
      and coal. Comparison to other areas in the world, the Sigma PAHs residual levels
      in underground river water in Dashiwei Tiankeng group is at the low level. In six
      sections, concentrations of benzo[a]pyrene (BaP) in surface water exceed the
      state quality standards.

PMID- 21717752
TI  - [Levels, distribution and possible sources of polybrominated diphenyl ethers in
      river sediments from an electronic waste recycling area].
AB  - The concentrations of 41 polybrominated diphenyl ethers (PBDEs) in the river
      sediments from Luqiao were analyzed by GC-NCI-MS. The objectives of this study
      were to understand the contents, spatial distribution and sources. The Sigma40
      PBDEs (excluding BDE209) concentrations in sediments sampled were in the range of
      0.177 to 161 ng x g(-1), with a mean of 22.5 ng x g(-1), and the concentrations
      of BDE209 were from 0.36 to 958 ng x g(-1), with a mean of 148 ng x g(-1). Deca
      BDE was the most predominant in 9 PBDE homologues in most of samples, accounting
      for 38.4%-96.0%, with an average of 74.4% nona-BDEs and hepta-BDEs, accounting
      for 3.3%-25.8% and 0.01%-14.1%, respectively. Significant correlations were
      observed among all of PBDEs congeners, which suggested these PBDEs might have the
      similar sources. The homologue composition of PBDEs and hierarchical cluster
      analysis (HCA) showed that most of sampling sites were mainly polluted by deca
      BDE formulation, and others polluted by deca-BDE and octa-BDE formulations.
      Compared to other studies from different countries and regions, the PBDEs
      concentrations in the present study were at a medium-to-low level. But it should
      be concerned that a few of sampling sites were highly contaminated by point
      sources.

PMID- 21717753
TI  - [Distribution and sources of PAHs in soil from Liaohe estuarine wetland].
AB  - 16 polycyclic aromatic hydrocarbons (PAHs) were measured by GC-FID for 31 surface
      soil samples collected from Liaohe estuary wetland in October of 2008 and May and
      August of 2009. The results showed that the total concentrations of PAHs in
      surface soil ranged from 293.4 ng x g(-1) to 1936.9 ng x g(-1) with a mean of
      851.5 ng x ng(-1). The contents of PAHs were the highest in the oilwell reed
      field and the lowest in the beach. The total concentrations of PAHs and
      proportion of median and high molecular weight of samples collected in October
      was higher than those collected in May and August. The relative abundance of
      different benzene rings and the ratio analysis illustrated that pyrolysis was the
      main source in October, and the mixed pollution of pyrogenic and oil spill was
      the dominant source in May and August. The principle component analysis-multiple
      linear regression analysis (PCA-MLR) indicated that the major source in October
      was coal/vehicular emission (accounted for 45.5%), and the mixture of vehicular
      exhaust and oil spill was the major source in May and August (accounted for 75.2%
      and 42.2% respectively).

PMID- 21717754
TI  - [Species sensitive distribution for aquatic biota exposed to triazophos].
AB  - The increasing pollution of organophosphorus pesticides (OP) in water have been
      of concerns. Taking the widely used triazophos as the object, a species
      sensitivity distribution (SSD) model was developed using a log-logistic
      distribution based on the median effective concentrations (EC50) of triazophos to
      aquatic species at various trophic levels, and then the model was tested and
      evaluated using probability plots and good-of-fit tests. The results showed that
      the SSD for aquatic biota exposed to triazophos was well fitted by a log-logistic
      distribution, which was totally determined by the two parameters, alpha = -0.4788
      and beta = 0.7546, with standard error 0.2381 and 0.1078 respectively. Based on
      the SSD model, the hazardous concentration for 5% of the species (HC5) and the
      criteria maximum concentration (CMC) of triazophos were 1.992 x 10(-3) mg/L and
      9.96 x 10(-4) mg/L, respectively. Through comparing the HC5 and CMC with the safe
      concentration for single-species, it could be found that environmental quality
      criteria derived from the SSD model was more strict, and closed to the real
      ecological environment. In addition, according to the reported data, the
      potentially affected fraction (PAF) of species exposed to triazophos in the
      Laizhou Bay (Bohai Sea, China) area was 0.36% predicted by the SSD model, and the
      corresponding risk might not be significant.

PMID- 21717755
TI  - [Toxicities of 30 ionic liquids to Vibrio qinghaiensis sp. Q67].
AB  - To systematically and effectively assess the toxic effects of "green solvent"
      ionic liquid (ILs) to a novel freshwater luminescent Vibrio qinghaiensis sp. Q67
      (Q67), the toxicities of 30 ILs with different alkyl chain lengths, anions and
      cation skeletons (methylimidazolium, dimethylimidazolium and pyridinium) were
      determined using the microplate toxicity analysis. The observed dose-response
      curves (DRCs) were fitted by using the nonlinear least square regression. It was
      shown that the DRCs of 30 ILs could be well described by the Logit or Weibull
      function (R > 0.98, RMSE < 0.053). The toxicities of 30 ILs varied greatly and
      the pEC50 values of 30 ILs ranged from 1.01 to 5.48. The toxicities of ILs to Q67
      mainly depended on the alkyl chain length and every two-carbon augment on the
      alkyl chain made the toxicity duplicate. The anions, cation skeletons and light
      absorbance of ILs showed no significant effect on the toxicities of ILs to Q67.

PMID- 21717756
TI  - [Analysis of methanogenic community of anaerobic granular sludge based on mcrA
      gene].
AB  - The methanogenic community in anaerobic granular sludge from a full-scale UASB
      treating avernectin wastewater was analyzed based on mcrA gene, compared to 16S
      rRNA gene. The results indicated that the diversity indices of methanogenic
      community, including Shannon diversity index, Margalef richness index and Berger
      Parker dominance index, were no difference between mcrA gene-based and 16S rRNA
      gene-based PCR products analysis by DGGE, although their DGGE band patterns were
      different, implying that the diversity analysis of methanogenic community based
      on mcrA genes was consistent with 16S rRNA gene. The phylogenetic analysis of
      dominant methanogenic populations based on these two target genes also showed
      resemble and Methanobacteriales and Methanosarcinales were determined to be the
      main orders of methanogenic populations in anaerobic granular sludge. On the
      other hand, the difference in phylogenetic analysis suggested simultaneously some
      group-specific of the two target genes. The hybridization of methanogenic
      community in FISH analysis based on two target genes was almost identical except
      a little different hybridization areas. The average relative abundance of
      methanogenic community was 24.25% +/- 6. 47% detected by FISH based on mcrA gene,
      lower than that based on 16S rRNA gene (33.42% +/- 2.34%). Then it could be
      concluded that the analysis of methanogenic community based on mcrA gene and 16S
      rRNA gene exhibited high resemblance and mcrA gene could used to be target gene
      for methanogenic community, as an alternative of 16S rRNA gene.

PMID- 21717757
TI  - [Evaluation of pathogen disinfection efficacy by chlorine and monochloramine
      disinfection based on quantitative PCR combined with propidium monoazide (PMA
      qPCR)].
AB  - A novel detection method of quantitative PCR combined with a DNA intercalating
      dye propidium monoazide (PMA-qPCR) was developed and then applied to analyze
      inactivation efficacy of chlorine and monochloramine on E. coli as a
      representative organism. The results shows that PMA removed 99.94% and 99.99% DNA
      from non-viable E. coli and Salmonella cells respectively and PMA-qPCR could
      effectively differentiate viable bacteria from non-viable bacteria; According to
      the first-order kinetic model, the inactivation coefficients on E. coli obtained
      by PMA-qPCR were 2.24 L x (mg x min)-1 and 0.0175 L x (mg x min)-1 for chlorine
      and monochloramine respectively, both of which were lower than those obtained by
      traditional plating counting method. In order to inactivate 99% of E. coli, the
      ct values by PMA-qPCR were 0.9 mg L(-1) min and more than 100 mg x L(-1) x min
      for chlorine and monochloramine while those by plating counting method were only
      0.6 mg x L(-1) x min and 20 mg x L(-1) min, respectively; E. coli concentration
      detected by conventional qPCR kept almost the same when ct value increased,
      indicating that conventional qPCR was unable to evaluate inactivation efficacy of
      both chlorine and monochloramine disinfection. In summary, PMA-qPCR shows to be a
      promising method for evaluating disinfection efficacy by chlorine and
      monochloramine more accurately.

PMID- 21717758
TI  - [Self-assembled gold nanoparticles modified electrode for electrochemical
      detection nitrite].
AB  - A modified sensor was fabricated by N-[3-(trimethoxysilyl) propyl]-ethylene
      diamine (TSPED) and colloidal gold particles (AuNPs) on glass carbon electrode
      (GCE). Atomic force microscopy (AFM) demonstrated that the colloidal gold
      particles were self-assembled onto the amine groups of the sol-gel. Due to the
      excellent electrocatalytic activity of gold nanoparticles toward the oxidation of
      nitrite and the interaction between the protonated TSPED film and the negatively
      charged nitrite, the operating potential for nitrite oxidation was shifted about
      140 mV to negative side, compared to bare GCE. The differential pulse voltammetry
      and the differential pulse amperometry were employed in the process of
      electrochemical measurements. Under the optimal conditions, a highly linear
      response to nitrite in the concentration range of 5.0 x 10(-7)-1.0 x 10(-3) mol x
      L- was observed, with a detection limit of 2.0 x 10(-7) mol x L(-1) (S/N = 3).
      The real water samples were investigated and the results were in good agreement
      with those obtained by standard spectrophotometric method. This method proposed
      by this paper possesses high sensitivity and good reproducibility.

PMID- 21717759
TI  - [Nitrogen balance and environmental impact of paddy field under different N
      management methods in Taihu Lake region].
AB  - Effects of nitrogen (N) management methods of paddy field on N export to
      environment and paddy N balance in Taihu lake region, China were studied. Field
      experiment including site-specific nitrogen management (SSNM), organic & chemical
      N fertilizer treatment (OCN), control released urea treatment (CRN), reduced
      chemical N treatment (RN) and farmer's N treatment (FN) were conducted at the
      Taihu lake region in 2008. N loss including runoff, leaching, ammonia
      volatilization and N2O were calculated, and the N balance was evaluated. Results
      showed the grain yield of SSNM, OCN, CRN and RN treatments was identical with FN
      treatment, while the total N rate reduced about 20%-40%, and N use efficiency
      (NUE) increased 14.5%-44%. N export of SSNM and CRN treatments decreased 52.8%
      and 45.4% in comparison with FN treatment. Under the same N input, N export of
      OCN treatment was lower than pure chemical N treatment (RN). N surplus was
      observed in FN treatment, while N deficit existed in SSNM treatments. CRN and
      SSNM treatments could increase NUE, reduce N export without sacrifice of yield
      and benefit, and could be as an economic and environment-friendly measure to
      intensify in Taihu lake region.

PMID- 21717760
TI  - [Contents and biodegradation of soluble organic carbon in different plant
      residues from the Loess Plateau].
AB  - Soluble organic carbon (SOC) in plant residues extracted by water or different
      extractants is an active component, and has important roles in carbon and
      nitrogen biogeochemical process in soil ecosystem. Reestablishing the vegetation
      on the Loess Plateau is changing the types and amounts of the plant residues into
      soil ecosystem. Therefore, our objective was to evaluate the contents and
      biodegradation of SOC of residues of different species from this region. Six
      species of plant residues were sampled from Shenmu, North of the Loess Plateau,
      and the contents of SOC in two sizes residues (2 mm and 1 cm length) was
      extracted with two extractants (distilled water and 0.01 mol x L(-1) CaCl2). And
      a 7-day incubation experiment (25 degrees C) was conducted to compare the
      biodegradability of SOC of the different plant residues. The contents of SOC in
      the different plant species ranged from 4.21 g x kg(-1) to 76.25 g x kg(-1), and
      the rates of SOC to total carbon (SOC/TC) of the plant residues were in range of
      0.99% and 19.84%. The order about the average content of SOC and SOC/TC of the
      different plant species was trees > shrubs > grasses. After 7-day of incubation,
      rates of biodegradation of SOC in different plant residues ranged from 34. 7% to
      75. 1% (averaged 56.3%). The proportion of complex structure SOC increased
      significantly in solution at the end of incubation, indicated the rapid
      biodegradation of labile composition in the residues.

PMID- 21717761
TI  - [Heavy metal contamination and Pb isotopic composition in natural soils around a
      Pb/Zn mining and smelting area].
AB  - The heavy metal (Pb, Zn, Cr, Cu, Cd, and Hg) concentrations in the A horizon and
      C horizon soils, collected around the Pb/Zn mining and smelting area of
      Shuikoushan in Hunan, China, were investigated, and the Pb isotopic compositions
      were also determined to identify the potential origin of Pb in the A horizon
      soil. Compared with C horizon soils, the A horizon soils exhibit elevated heavy
      metal concentrations, especially in the vicinity of the mining and smelting area.
      This reveals that the surface soil was contaminated to some degree. The contents
      of Pb, Zn, Cr, Cu, Cd, and Hg in soils are up to 3966.88, 2086.25, 135.31,
      185.63, 56.15, and 16.434 mg/kg, respectively. The potential risks caused by
      different metals are in the order of Cd > Hg > Pb > Cu > Zn = Cr. Much higher
      potential ecological risk was observed for the central area (Shuikoushan Pb/Zn
      mining and smelting area) than for the surrounding area. About 34%, 33%, 11%, and
      22% of the sampling sites demonstrate low, moderate, considerable, and very high
      potential ecological risk in the central area, while about 68%, 16%, 10%, and 6%
      of the sampling sites show low, moderate, considerable, and very high potential
      ecological risk in the surrounding area, respectively. Compared with the Pb
      isotopic compositions in the C horizon soils (206Pb/207Pb 1.168-1.246, 208 Pb/206
      Pb 2.014-2.130), the Pb in the A horizon soils has lower 206 Pb/207Pb ratios
      (1.166-1.226) and higher 208Pb/206Pb ratios (2.043-2. 135). The Pb in the A
      horizon soils predominantly derives from two-component mixing resources. One is
      the parent materials of C horizon, and the other is the atmospheric deposition of
      the smelting flue gas dust.

PMID- 21717762
TI  - [Distribution patterns of PAHs in soils from coking plant and the particle-size
      cut points of soil washing].
AB  - Soil particle size distribution and contaminants distribution patterns in
      different soil size fractions are the basis of soil treatability using soil
      washing method. Soil particle-size cut points are important parameters of soil
      washing process. According to ex situ soil washing technology, soil samples were
      collected in a former coking plant. The soil particle size distribution and the
      concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in USEPA priority
      list were analyzed. Tween 80 and Triton X-100 solutions were used to clean the
      polluted soil with different particle size. Results showed that the total
      concentrations of 16 PAHs ranged from 6.27 to 40.18 mg/kg dry weight in the six
      soil size fractions and present a bimodal distribution. The maximum individual
      PAH concentration mostly occurred in the 250-500 microm size fraction. The lowest
      individual PAH concentration was in the 50-75 microm size fraction. The removal
      efficiencies of PAHs in different soil size fractions depended on their initial
      concentrations and the characteristics of soil. The PAHs removal efficiencies in
      coarser size fractions were lower than that in the finer size fractions owing to
      their higher organic carbon content. Based on the removal efficiency of PAHs in
      each soil size fractions by surfactant solution and the requirements of waste
      volume reduction, 50 microm was determined as the particle-size cut point. Then,
      82.95% volume reduction can be achieved.

PMID- 21717763
TI  - [Uptake of radionuclides from soil to plant and the discovery of 226Ra, 232Th
      hyperaccumulator].
AB  - 11 sorts of plant samples and corresponding soil samples were collected in
      Conghua and Taishan, Pearl River Delta. The specific activity of 238U, 226Ra,
      232Th and 40K of samples were investigated by using HPGe-gamma-ray spectra
      analysis. The results showed that the average specific activity of 238U, 226Ra,
      232Th and 40K in soil samples were 151.8, 146.3, 226.6, 665.5 Bq/kg, which were
      higher than the average values of China and the world. The concentration of 238U
      in all sort of plants are very low and most of them are lower than detection
      limit, while the values of 226Ra, 232Th and 40K were high. The contents of 226Ra
      and 232Th in Dicranopteris dichotoma were the highest, whose average specific
      activity is 285.9, 986.2 Bq/kg respectively. The average bioconcentration factors
      (BFs)of 26Ra, 232Th of Dicranopteris dichotoma were 2.20, 4.23, respectively, the
      other 10 sort of plants have BFs of 2266Ra, 232Th were in the range of 10(-1)-10(
      2). The bioconcentration factors and the translocation factors of 226Ra, 232Th of
      Dicranopteris dichotoma. were all bigger than 1, so Dicranopteris dichotoma can
      be defined as hyperaccumulator of 226Ra and 232Th.

PMID- 21717764
TI  - [Effects and mechanism of alkaline wastes application and zinc fertilizer
      addition on Cd bioavailability in contaminated soil].
AB  - The effects of paper mill sludge, red mud and zinc fertilizer addition on
      remediation of acid cadmium contaminated paddy soil were studied in a pot
      experiment, and their beneficial effects were verified in a field experiment, by
      using lime as comparison. The pot experiment results showed that a single
      application (2 g x kg(-1)) of lime, paper mill sludge or red mud increased soil
      pH significantly. Compared with no applying alkaline substances, the soil
      exchangeable Ca content was increased by 33.1%-76.0% at 7 days after applying
      alkaline substances and 31.0%-78.3% at 30 days after rice transplanting,
      respectively. The soil available Cd content was significantly decreased by 38.4%
      45.0% at 7 days after the three alkaline substances applications, and was
      decreased by 37.4%-52.9% and 33.2%-38.7% at 30 days and 60 days after rice
      transplanting, respectively. The Cd content in rice root and brown rice was
      decreased by 24.0%-48.5% and 26.3%-44.7%, respectively. With equal applications
      of lime, paper mill sludge and red mud, the effects on increase of soil pH and
      decrease in Cd accumulation by rice was lime > red mud > paper mill sludge.
      Compared with a single application (2 g x kg(-1)) of paper mill sludge or red
      mud, Cd accumulation decreased significantly following the application of zinc
      fertilizer (0.2 g x kg(-1)) field experimental results were similar to the pot
      experiment that Cd accumulation apparently declined in the first and second crops
      (late rice and autumn rape) following the application of paper mill sludge, red
      mud and addition of zinc fertilizer. The Cd content in brown rice and rape seeds
      was decreased by 27.1-65.1% and 16.4%-41.6%, respectively, compared with no
      alkaline substances application. The Cd content in brown rice reached the
      National Hygienic Standard for Grains (GB 2715-2005). Therefore, combined
      application of paper mill sludge or red mud with zinc fertilizer was a feasible
      method to remediate acid cadmium contaminated paddy soil. Rice quality was
      guaranteed by determination of rational amount of alkaline wastes and a
      proportion of zinc fertilizer which was in accord with soil Cd contamination
      level and chemical properties, etc.

PMID- 21717765
TI  - [Effect of phosphor on accumulation and chemical forms of cadmium, and
      physiological characterization in different varieties of Capsicum annuum L].
AB  - Pot experiments were carried out to investigate the influence of different
      Phosphor (P) levels (0, 0.3% and 0.5%) on the plant growth, activities of
      antioxidant enzymes, accumulation and chemical forms of cadmium (Cd) in Capsicum
      annuum L. when exposed to Cd (10 mg x kg(-1)). The results showed that dry
      weights of leaf, fruit, roots and total dry weights of plant, and concentration
      and accumulation of Cd significantly differed between two varieties of Capsicum
      annuum L. Dry weights of fruit and total plant of Chaotianjiao increased by P
      (0.3% and 0.5%), while that of Yanjiao425 was inhibited. Activities of catalase
      (CAT) were increased at first, and then reduced in the presence of P; Activities
      of superoxide dismutase (SOD) and peroxidase (POD) of Chaotianjiao increased with
      increasing levels of P, but activities of SOD and POD of Yanjiao425 decreased
      with increasing levels of P. Chemical forms of Cd in fruit of Capsicum annuum L.
      were in order of F(NaCl) > F(HAC) > F(E) > Fr > F(HC) > F(W). The total
      extractable Cd, ethanol-extractable Cd, hydrochloric acid-extractable Cd and
      residual Cd in fruit of Ynajiao425 obviously decreased in the presence of P
      compared to the control, while the total extractable Cd, water-extractable Cd,
      acetic acid-extractable Cd and residual Cd in fruit of Chaotianjiao increased.
      Cadmium accumulations of Capsicum annuum L. were in order of roots > stew > leaf
      > fruit. Cadmium accumulations in fruit and plant of Yanjiao425 were decreased by
      47.7% and 58.5% , 5.5% and 13. 1% in the presence of 0.3% and 0.5% P when exposed
      to Cd, and Cd accumulations in fruit and plant of Chaotianjiao were decreased by
      23.6% in the presence of 0.3% P.

PMID- 21717766
TI  - [Nitrate contents in autumn vegetables and assessment of nitrate intake in
      Shanghai].
AB  - To analyze and assess the nitrate contents in Autumn vegetables and nitrate
      intake in Shanghai resident 25 groups and 439 various vegetables were collected
      and analyzed from the green houses and outdoors in Songjiang, Fengxian, Jinshan
      and Pudong of Shanghai during Sep.-Nov., 2009. Nitrate contents were analyzed by
      UV-spectrophotometer. The results showed that the prevalence of severe
      contamination was 41.46%, the prevalence of heavy and medium contamination was
      30.53%, the prevalence of mild contamination was 28.02%; the content of nitrate
      in vegetables was in the following descent order: leafy vegetables, root and stem
      vegetables, melons, egg plants, beans, the nitrate contents in different species
      differed greatly; the nitrate contents in leafy, root and stem vegetables with
      green-house planting were less than that of outdoor planting in Fengxian and
      Songjiang except Pudong and Jinshan. According to the assessment of nitrate
      intake, the average daily intake of local resident is 445.22 mg which exceeds ADI
      38.42%, so limited standard and control are urgently needed.

PMID- 21717767
TI  - [Concentrations and distribution of tetracycline antibiotics in vegetable field
      soil chronically fertilized with manures].
AB  - Occurrence of antibiotics in the soils substantially fertilized with antibiotics
      enriched animal manures is very of concern. This paper investigated the
      concentration and distribution of four tetracycline antibiotics in soils from
      vegetable field chronically fertilized with manures in subtropical area using
      solid-phase extraction followed by high-performance liquid chromatography
      electrospray ionization tandem mass spectrometry (HPLC-MS/MS). The sum
      concentrations of four tetracycline compounds ranged from 1.35 microg/kg to 22.52
      microg/kg with an average of 7.35 microg/kg. There were thirty one to one hundred
      percent of the soil samples were detected with average concentrations of 0.63-
      3.11 microg/kg for four tetracycline compounds which dominated mostly with
      oxytetracycline and secondly with deoxytetracycline. Composition and levels of
      tetracycline compounds varied obviously in both horizontal and vertical soils.
      The concentration of tetracycline compounds in soil profile decreased rapidly
      with the depth and some of the compounds were still detected in 60 to 80
      centimeter depth of soil. It is concluded that tetracycline antibiotics in soils
      from vegetable field chronically fertilized with manures in subtropical area were
      generally lower and less ecotoxic risk for soil ecosystem. But it should not be
      ignored in view of combined toxic effect and resistance of various compounds.

PMID- 21717768
TI  - [Occurrence of quinolone and sulfonamide antibiotics in swine and cattle manures
      from large-scale feeding operations of Guangdong Province].
AB  - The occurrence and distribution of four quinolones and four sulfonamides in swine
      and cattle feces sampled from twenty large-scale feeding operations in different
      areas of Guangdong province were detected using solid phase extraction (SPE) and
      high performance liquid chromatography (HPLC). Quinolone and sulfonamide
      compounds were observed in all pig dung samples. Their total concentrations
      ranged from 24.5 microg/kg to 1516.2 microg/kg (F. W.) with an average of 581.0
      microg/kg and ranged from 1925.9-13399.5 microg/kg with an average of 4403.9
      microg/kg respectively. The dominant compounds in pig feces were ciprofloxacin
      and enrofloxacin for quinolones and sulfamerazine and sulfamethoxazole for
      sulfonamides. Quinolone compounds which dominated with norfloxacin and
      ciprofloxacin were also observed in all cattle dung samples, its total
      concentrations ranged from 73.2 microg/kg to 1328.0 microg/kg which averaged
      572.9 microg/kg. While the positive rates of sulfonamide compounds detected in
      cattle dung samples were above 90%, predominated by sulfamethoxazole and
      sulfamerazine. Concentration and distribution of both quinolone and sulfonamide
      compounds in swine and cattle dungs of different feeding operations varied
      greatly. Relatively high concentrations of the two kinds of antibiotics were
      found in both swine and cattle dungs from Guangzhou area, while sulfameter and
      sulfamethazine in cattle dungs from Foshan and Shenzhen areas were below the
      limit of detection.

PMID- 21717769
TI  - [Characteristics of microbial community and operation efficiency in biofilter
      process for drinking water purification].
AB  - In order to explore characteristics of microbial community and operation
      efficiency in biofilter (biologically-enhanced active filter and biological
      activated carbon filter) process for drinking water purification, Biolog and
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      techniques were applied to analyze the metabolic function and structure of
      microbial community developing in biofilters. Water quality parameters, such as
      NH; -N, NO; -N, permanganate index, UV254 and BDOC etc, were determined in inflow
      and outflow of biofilters for investigation of operation efficiency of the
      biofilters. The results show that metabolic capacity of microbial community of
      the raw water is reduced after the biofilters, which reflect that metabolically
      active microbial communities in the raw water can be intercepted by biofilters.
      After 6 months operation of biofilters, the metabolic profiles of microbial
      communities are similar between two kinds of biologically-enhanced active
      filters, and utilization of carbon sources of microbial communities in the two
      filters are 73.4% and 75.5%, respectively. The metabolic profiles of microbial
      communities in two biological activated carbon filters showed significant
      difference. The carbon source utilization rate of microbial community in granule
      activated carbon filter is 79.6%, which is obviously higher than 53.8% of the
      rate in the columnar activated carbon filter (p < 0.01). The analysis results of
      PCR-SSCP indicate that microbial communities in each biofilter are variety, but
      the structure of dominant microorganisms is similar among different biofilters.
      The results also show that the packing materials had little effect on the
      structure and metabolic function of microbial community in biologically-enhanced
      active filters, and the difference between two biofilters for the water
      purification efficiency was not significant (p > 0.05). However, in biological
      activated carbon filters, granule-activated carbon is conducive to microbial
      growth and reproduction, and the microbial communities in the biofilter present
      high metabolic activities, and the removal efficiency for NH4(+)-N, permanganate
      index and BDOC is better than the columnar activated carbon filter(p < 0.05). The
      results also suggest that operation efficiency of biofilter is related to the
      metabolic capacity of microbial community in biofilter.

PMID- 21717770
TI  - [Spatial difference of microbial community structure and enzyme activity in
      constructed wetlands receiving wastewater containing heavy metals].
AB  - The microbial community structure and enzyme activity were investigated in the
      three-stage wavy subsurface constructed wetland (W-SFCW) receiving wastewater
      containing heavy metals (Cr, Cu and Ni). Colony forming units (CFU) abundance of
      microbes was calculated by using plate culture. The microbial community structure
      was investigated by using PCR-DGGE and sequencing. Enzyme activity was detected
      by using colorimetry. The results showed that the CFU of bacteria ranged from
      (4.10 +/- 0.72) x 10(6) to (1.61 +/- 0.10) x 10(7), fungi ranged from (7.21 +/-
      1.60) x 10(4) to (1.29 +/- 0.02) x 10(5) and actinomycetes ranged from (1.41 +/-
      0.27) x 10(6) to (3.38 +/- 0.11) x 10(6). All of 8 bands retrieved from DGGE gels
      were unique 16S rRNA or 18S rRNA sequences and revealed that the microbial
      community structures had changed spatially. Maximum urease [(0.67 +/- 0.2) mg/(g
      x 24 h)], invertase [(40.15 +/- 0.14) mg/(g x 24 h)] and alkaline phosphatase
      [(1.03 +/- 0.16) mg/(g x 2 h)] activities were at first stage, third stage and
      first stage, respectively. A negative correlation between fungi CFU abundance and
      the total content of Cr, available Cr content and activation rate of Cr was
      detected, a negative correlation was also found between the invertase activity
      and total Cu and Ni contents and the Ni activation rate.

PMID- 21717771
TI  - [Experimental study of autotrophic denitrification bacteria through
      bioaugmentation of activated sludge from municipal wastewater plant].
AB  - Activated sludge of municipal wastewater treatment plant was domesticated by
      sulfur as the electron donor under autotrophic. The sludge activity was
      determined by measuring growth rate of sludge. The removal efficiency of nitrate
      and sulfate production efficiency were analyzed by continuously measuring the
      concentration of NO3(-)-N and SO4(2-). When the removal efficiency of nitrate was
      more than 90%, 16S rRNA genetic libraries were built up to compare their
      microbial biodiversity. The growth rate of sludge is 0.177 g/(L x d). The
      relation between concentration of nitrate and time meets first order reaction
      kinetics. The bacteria in the sludge affiliated with Beta-Proteobacteria, Deta
      Proteobacteria, Gamma-Proteobacteria and Unclassified bacteria. Beta
      Proteobacteria is the main phylum in the sludge. Bacteria related to Thiobacillus
      denitrificans from denitrifying bioreactor perform 48.65%. In addition, the
      bacteria of Denitratisoma sp., Curvibacter sp., Thermomonas sp., Geobacter sp.
      are existed in the sludge. The study of autotrophic denitrifying bacteria
      diversity is conducive to optimization of reaction conditions and efficient
      removal of nitrate.

PMID- 21717772
TI  - [Effect of different intensities of electroacupuncture on expression of monocyte
      chemoattractant protein-1 and TNF-alpha in adipose tissue in obesity rats].
AB  - OBJECTIVE: To observe the effect of different intensities of electroacupuncture
      (EA) on adipose tissue inflammatory cytokines in rats with simple obesity so as
      to investigate its mechanism underlying body weight reduction. METHODS: Forty SD
      male rats were randomly divided into normal, model, strong EA and weak EA groups
      (n = 10/group). Obesity model was established by feeding the rats with high fat
      diet. EA (20 Hz, strong EA: 5 V, weak EA: 2. 5 V) was applied to "Zusanli" (ST
      36) and "Sanyinjiao" (SP 6) for 15 min, once everyday and for 14 days. Body
      weight and Lee's index (= body weight(1/3) x 10(3) / body length) were detected.
      The fasting blood glucose was detected by hexokinase method, serum triglyceride
      (TG) was detected by glycerol-phosphoric acid oxidase peroxydase (GPO-POD)method,
      total cholesterol (TC) was detected by cholesterol oxidase method, high density
      lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-O)
      were measured by using one-step method, respectively. The expression of monocyte
      chemoattractant protein-1 (MOP-1) mRNA and tumor necrosis factor (TNF)-alpha mRNA
      in the epididymis adipose tissue was detected by reverse transcription-polymerase
      chain reaction (RT-POR). RESULTS: In comparison with the normal group, the body
      weight, Lee's index, blood lipid (TG, TC, LDL-C), fasting blood glucose levels,
      and expression of MOP-1 mRNA and TNF-alpha mRNA were significantly higher in the
      model group (P < 0.01), and HDL-C was significantly lower (P < 0.01). After
      EA,compared with the model group, the body weight, Lee's index, TG, TC, LDL-C,
      fasting blood glucose levels, and expression of MCP-1 mRNA and TNF-a mRNA in both
      strong and weak EA groups were significantly decreased (P < 0.01, P < 0.05), and
      HDL-C was significantly increased (P < 0.01, P < 0.05). The effects of strong EA
      group were obviously superior to those of weak EA group (P < 0.05, P < 0.01). No
      statistical significance was observed between the two EA groups in fasting blood
      glucose levels (P > 0.05). CONCLUSION: EA of "Zusanli" (ST 36) and "Sanyinjiao"
      (SP 6) has a beneficial weight-reduction effect on rats with simple obesity, and
      moreover, the effect of strong EA stimulation is evidently superior to weak EA
      stimulation.

PMID- 21717773
TI  - [Effects of acupoint-injection of compound Angelica-root Injectio on cerebral Bcl
      2 and Bax immunoactivity and hemorheology in rats with cerebral ischemia
      reperfusion injury].
AB  - OBJECTIVE: To observe the effect of acupoint-injection on the expression of Bcl-2
      and Bax in the cerebral tissue around the ischemic area in cerebral ischemia
      reperfusion (CI/R) rats so as to investigate its mechanism underlying improvement
      of cerebral infarction. METHODS: Forty-eight Wistar rats were randomized into
      sham operation (sham), model and acupoint-injection groups (n = 16/group). CI/R
      model was duplicated by occlusion of the middle cerebral artery for 2 h and
      reperfusion for 24 h. "Baihui" (GV 20) and "Dazhui" (GV 14) were used for
      injection of Fufang Danggui Zhusheye (Compound Angelica-root Injectio, 1000
      g/mL), immediately 6 h, 12 h and 24 h after modeling. Bcl-2 and Bax
      immunoactivity in the cerebral tissue around the ischemic area was assayed by
      immunohistochemistry. Blood viscosity including high, medium and low shearing
      rates, erythrocyte aggregation index (AI), rigidity index (RI) and deformity
      index (DI) were assayed by using a full-automatic hemorheolometer. RESULTS: In
      comparison with the sham group, the numbers of both Bcl-2 and Bax immunoreaction
      (IR) positive cells in the ischemic cerebral tissue in the model group were
      increased significantly (P < 0.05). Compared with the model group, the number of
      Bcl-2 IR-positive cells was increased further apparently in the acupoint
      injection group (P < 0.05), while that of Bax IR-positive cells in the acupoint
      injection group lowered considerably (P < 0.05). The ratio of Bcl-2/Bax was
      decreased significantly in the model group than that in the sham group (P <
      0.05), and increased evidently in the acupoint-injection group than in the model
      group (P < 0.05). Regarding the parameters of hemorheology, compared to the sham
      group, the high, medium and low shear rates, erythrocyte AI and RI were increased
      significantly in the model group (P < 0.05), while DI was decreased significantly
      (P < 0.05). Compared to the model group, the high, medium and low shear rates,
      and erythrocyte AI and RI in the acupoint-injection group were down-regulated
      significantly, and DI of the acupoint-injection group was up-regulated markedly
      (P < 0.05). CONCLUSION: Acupoint-injection of Compound Angelica-root Injectio can
      function in up-regulating CI/R induced increase of cerebral Bcl-2 expression and
      suppressing CI/R induced increase of cerebral Bax expression, blood viscosity,
      and erythrocyte AI and RI, and inhibiting CI/R induced decrease of erythrocyte DI
      in CI/R rats, which may contribute to its effects in improving cerebral ischemia
      by resisting neuronal apoptosis and facilitating cerebral blood circulation.

PMID- 21717774
TI  - [Effect of "Xiusanzhen" on hippocampal muscarinic cholinergic receptor activity
      in Alzheimer disease rats].
AB  - OBJECTIVE: To explore the effect of "Xiusanzhen" [electroacupuncture (EA) of
      bilateral "Yingxiang" (LI 20) and "Yintang" (EX-HN 3)] on activities of
      hippocampal muscarinic cholinergic receptor (mAChR) and the involved neural path
      in Alzheimer Disease(AD)rats. METHODS: Forty Sprague Dawley rats were randomly
      divided into normal control, model, olfactory nerve severing (ONS)-EA of
      "Xiusanzhen" (ONS-EA) and EA of "Xiusanzhen" (EA) groups. AD model was
      established by intra-hippocampal injection (AP: 3.5 mm, L:2 mm, H: -2.8 mm) of
      Abeta(1-40) starch-like peptide (10 microg/2 microL) under the aid of a
      microsyringe installed in a brain stereotaxis instrument. For rats of the ONS-EA
      group, the olfactory nerve was severed by using a surgical knife after drilling a
      hole on the skull (5 mm anterior to the bregma, L, R: 2 mm). The mAChR density,
      and its maximum binding capacity (Bmax) and dissociation constant (Kd) of the
      hippocampus tissue were measured by using radio-ligand binding analysis and
      Lowry's microamount protein assay. RESULTS: In comparison with the normal control
      group, the hippocampal mAChR density and its Bmax in the model group were
      decreased remarkably (P < 0.05), while the Kd of M-receptor in the model group
      was increased remarkably (P < 0.05). In comparison with the model group,
      hippocampal mAChR density and its Bmax in the EA group were up-regulated
      obviously (P < 0.05), while the Kd of mAChR in the EA group was down-regulated
      significantly (P < 0.05). No significant differences were found between the model
      and ONS-EA groups in mAChR density and its Bmax and Kd (P > 0.05). CONCLUSION:
      "Xiusanzhen"-EA can effectively up-regulate hippocampal mAChR density and Bmax
      and down-regulate Kd of M-receptor of hippocampus in AD rats, which is dependent
      on the intact olfactory nerve pathway.

PMID- 21717775
TI  - [Effect of electroacupuncture on learning-memory ability, and Abeta and LRP1
      immunoactivity in hippocampal sulcus microvessels in APP transgenic mice].
AB  - OBJECTIVE: To investigate the effect of electroacupuncture (EA) of "Baihui" (GV
      20) and "Yongquan" (KI 1) on the expression of amyloid beta protein (Abeta) and
      low density lipoprotein (LDL) receptor-related protein 1 (LRP 1) in the
      hippocampal sulcus microvessels in amyloid precursor protein (APP) 695 V717 I
      transgenic mice, so as to study its mechanism underlying relief of Alzheimer
      Disease (AD). METHODS: Twelve APP 695 V717 I transgenic mice were randomly
      divided into model group and EA group. Six C 57 BL/6 mice were used as the
      control group. EA (2 Hz/100 Hz, 3-5 mA) was applied to "Baihui" (GV 20) and
      "Yongquan" (KI 1) for 15 min, once every other day for three months. The learning
      memory ability of mice was detected by using Lashley III water maze system. The
      expression level of Abeta(1-42), and LRP 1 in the hippocampal sulcus microvessels
      were measured by immunohistochemistry. RESULTS: Water maze test showed that the
      swimming duration from the start to the goal box (terminal) in the Lashley III
      water maze was significantly longer in the model group than in the control group
      (P < 0.05), suggesting a markedly lower learning-memory capacity of APP 695 V717
      I transgenic mice. Compared with the model group, the swimming duration in the EA
      group was decreased considerably (P < 0.05). The integrated optical density (IOD)
      value of hippocampal Abeta(1-42) immunoreaction (IR) positive products in the
      model group was significantly higher than that in the control group (P < 0.01)
      and the IOD value of hippocampal LRP 1 IR-positive products in the model group
      was apparently lower than that in the control group (P < 0.01). In comparison
      with the model group, the IOD value of Abeta(1-42) IR-positive products in the EA
      group was obviously lower than that in the model group (P < 0.05), while that of
      LRP 1 IR-positive products in the EA group was significantly higher than that in
      the model group (P < 0.05), suggesting down-regulation of hippocampal Abeta(1-42)
      expression and up-regulation of LRP 1 expression after EA, and reduction of
      deposition of Abeta in the cerebral microvessels after EA. CONCLUSION: EA can
      improve the learning-memory capacity of APP transgenic mice, which is closely
      related to its effects in up-regulating hippocampal LRP 1 expression and down
      regulating hippocampal Abeta(1-42) expression.

PMID- 21717776
TI  - [Effects of oculo-acupuncture therapy on colonic serotonin reuptake transporter
      expression in rats with irritable bowel syndrome].
AB  - OBJECTIVE: To investigate the effect of oculo-acupuncture therapy (OAT) on the
      alteration of colonic serotonin reuptake transporter (SERT) expression in rats
      with irritable bowel syndrome (IBS) so as to explore its underlying mechanism in
      relieving IBS. METHODS: Thirty male Wistar rats were randomized into control, IBS
      model and OAT groups (n = 10/group). IBS model was established by repeated stress
      stimulation [water-intake inhibition (24 h), warm box keeping (40 degrees C,5
      min), electric shock stimulation (30 V, 120 s), forced cool water swimming (14 t,
      5 min), 24 h fasting, and tail clamping (180 s)] for 18 days. Oculo-acupuncture
      stimulation was given to "Xiajiao" (Lower Energizer), "Dachang" (Large
      Intestine), "Gan" (Liver) and "Pi" (Spleen) areas for 20 min by using filiform
      acupuncture needles (manipulated 1 min once every 10 min). The treatment was
      conducted once every 12 h for 7 days. Colonic SERT mRNA and protein expression
      levels were examined by RT-PCR and Western Blot. RESULTS: In comparison with the
      control group, the expression levels of both colonic SERT mRNA and protein in the
      model group were down-regulated remarkably (P < 0.05). Compared with the model
      group, the expression levels of SERT gene and protein in the OAT group were
      increased remarkably (P < 0.05). CONCLUSION: OAT can increase colonic SERT
      protein and gene expression in IBS rats, which may play a role in relieving IBS
      in OAT clinic.

PMID- 21717777
TI  - [Effect of moxibustion on ultrastructure of synovial cells in rheumatoid
      arthritis rats].
AB  - OBJECTIVE: To observe the influence of moxibustion of "Shenshu"(BL 23) and
      "Zusanli" (ST 36) on the microstructure of synovial cells in the knee-joint in
      rheumatoidarthritis (RA) rats so as to study its underlying mechanism in anti
      inflammatory immune effect. METHODS: A total of 120 Wistar rats were randomized
      into normal control, model, acupuncture, moxibustion, CO2-laser and medication
      groups (n = 20/group). RA model was duplicated by raising the rats in a windy
      (electro-fan blowing), cold [(6 +/- 2) degrees] and wet (80%-90%) environment for
      12 h/d and 20 days, followed by injecting Freund's complete adjuvant (0.15 mL)
      into the rat's ankle. Moxibustion or acupuncture or CO2 laser (10.6 microm)
      irradiation was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36) for 20 min,
      once daily for 15 days. Intragastric perfusion of Leigongteng (Tripterygium
      Wilfordii Hook.f.) was given to medication group, 8 mg/kg, once daily for 15
      days. The thoracic gland index [weight of the thoracic gland (mg)/ body weight
      (g) x 100%] and spleen index [weight of the spleen (mg)/body weight (g) x 100%]
      were calculated after killing the rats under anesthesia. The ultrastructure of
      synovial cells of the knee-joint was observed by using transmission electron
      microscopy. RESULTS: In comparison with the normal control group, the thoracic
      gland index in the model group was decreased significantly (P < 0.01), while the
      spleen index of the model group increased considerably (P < 0.05). In comparison
      with the model group, the thoracic gland indexes in the acupuncture, moxibustion,
      CO-laser and medication groups were increased significantly (P < 0.05, P < 0.01),
      whereas the spleen indexes in the four groups decreased evidently (P < 0.05). No
      significant differences were found among the acupuncture, moxibustion, CO2-laser
      and medication groups in up-regulating the thoracic gland index and down
      regulating the spleen index (P > 0.05). After modeling, the synoviocytes of the
      knee-joint were impaired remarkably, exhibiting incomplete cellular membrane,
      some prolapsed organelles, marginalized stained granules in the cellular nucleus,
      vague nuclear membrane, enlarged rough endoplasmic reticulum, reduction in the
      number of mitochondria with vacuolization degeneration and multiple lysosomes.
      But, the pathological changes of the ultrastructure of most synoviocytes in the
      acupuncture, moxibustion, CO2-laser and medication groups were relatively milder.
      CONCLUSION: Moxibustion can protect the immune organs (thoracic gland and spleen)
      from injury and improve pathological changes of the ultrastructure of local
      synoviocytes in RA rats.

PMID- 21717778
TI  - [Randomized controlled clinical trials of red-hot filiform needle puncturing for
      knee ostarthritis and inflammatory cytokines in knee articular fluid in senile
      knee ostarthritis patients].
AB  - OBJECTIVE: To observe the effect of red-hot filiform needle puncturing on the
      pain severity of knee ostarthritis (OA) and the inflammatory cytokine levels in
      the knee articular cavity (KAC) fluid in senile knee OA patients so as to find a
      better therapy for knee OA. METHODS: A total of 200 senile knee OA outpatients
      (who signed an informed consent) were randomized into treatment group and control
      group (n = 100/group) according to a random number table and their visiting
      sequence. Futu (LI 18), Neixiyan (EX-LE 4), Yanglingquan (GB 34), Yinlingquan (SP
      9), Zusanli (ST 36), etc. on the affected side of the body were punctured with
      red-hot filiform needles (cauterized on an alcohol burner) or routine filiform
      needles, with the needles retained for 30 min. The treatment was conducted once
      every other day, 15 sessions altogether. Before and after the treatment, the
      patients' KAC fluid was sampled for assaying the contents of IL-1, IL-6 and tumor
      necrosis factor (TNF)-alpha with enzyme-linked immunosorbent assay (ELISA). The
      pain severity was tested by using visual analogue scale (VAS) and the
      comprehensive therapeutic effect was evaluated by using clinical symptoms and
      signs, functional activity and pain degrees. RESULTS: In comparison with pre
      treatment, IL-1, IL-6 and TNF-alpha contents in KAC fluid were decreased
      significantly in both treatment and control groups (P < 0.01). The IL-1, IL-6 and
      TNF-alpha levels were considerably lower in the treatment group than in the
      control group following the treatment (P < 0.01), suggesting a marked relief of
      inflammation in the affected knee joint. Compared to pre-treatment, the severity
      scores of illness state of both treatment and control groups were decreased
      remarkably (P < 0.01), and the VAS score of the treatment group was significantly
      lower than that of the control group after the treatment (P < 0.05). Of the two
      100 knee OA outpatients in the treatment and control groups, 29 (29%) and 21
      (21%) were controlled in their symptoms and signs; 46 (46%) and 34 (34%)
      experienced apparent improvement; 18 (18%) and 29 (29%) were effective; 7 (7%)
      and 16 (16%) failed in the treatment. The comprehensive therapeutic effect of the
      treatment group was significantly superior to that of the control group (P <
      0.01). CONCLUSION: Red-hot filiform needle puncturing is superior to routine
      filiform needle puncturing in relieving senile knee OA and in reducing
      inflammatory cytokine levels in knee OA patients.

PMID- 21717779
TI  - [Clinical randomized controlled trials of treatment of neck-back myofascial pain
      syndrome by acupuncture of Ashi-points combined with moxibustion of heat
      sensitive points].
AB  - OBJECTIVE: To observe the therapeutic effect of acupuncture of Ashi points in
      combination with moxibustion of heat-sensitive points for neck-back myofascial
      pain syndrome, so as to find a better combined therapy. METHODS: A total of 62
      eligible patients were randomly divided into treatment group (acupuncture of Ashi
      points plus moxibustion of heat-sensitive points, n=32) and control group
      (acupuncture of Ashi-points plus TDP irradiation, n=30) by using single-blind
      method. Ashi-points were the tenderpoints or subcutaneous induration spots
      determined by digital pressure in the focus region, and the heat-sensitive points
      were the acupoints around the subcutaneous induration spots in the neck-back
      regions determined by patients' feeling (heat from the ignited moxa transmitting
      toward the deep muscle layer, extending toward the surrounding region of the Ashi
      points, etc. and the distal part of the body) during moxibustion. Ashi-points
      were punctured with filiform needles and stimulated with reducing method by
      lifting, thrusting and twirling the acupuncture needle repeatedly till "Deqi",
      followed by retaining the needle for 30 min. Moxibustion was given to the
      patients for 10-90 min (when the patient began to feel heat penetrating into the
      deeper muscle layer to the termination of the heat transmission). TDP irradiation
      was given to the Ashi-points for 30 min in every session of treatment. The
      treatment was conducted once daily, 5 times a week, two weeks altogether. McGill
      pain questionnaire containing pain rating index (PRI), visual analogue scale
      (VAS) and present pain intensity (PPI) and "the criteria for assessing the
      therapeutic effect of back-myofascitis" recorded in "Standards for Diagnosis and
      Efficacy Evaluation of Clinical Conditions in Chinese Medicine" (published in
      1994 in China) were used to evaluate the analgesic effect. RESULTS: Before the
      treatment, no significant differences were found between the treatment and
      control groups in PRI, VAS and PPI. After the treatment, PRI, VAS and PPI were
      all significantly lower in the treatment group than in the control group (P <
      0.01). Of the 32 and 30 myofascitis patients in the treatment and control groups,
      11 (34.4%) and 3 (10.0%) were cured, 20 (62.5%) and 25 (83.3%) experienced
      improvement in their symptoms, 1 (3.1%) and 2 (6.7%) had no apparent changes. The
      cure rate of the treatment group was significant bigger than that of the control
      group (P < 0.05). CONCLUSION: Acupuncture combined with moxibustion of Ashi
      points can effectively relieve pain reaction in neck-back myofascial pain
      syndrome patients, which is significantly superior to that of acupuncture plus
      TDP irradiation therapy.

PMID- 21717780
TI  - [Effect of acupuncture on heroin cue-induced functional magnetic resonance images
      in heroin-addicted human subjects].
AB  - OBJECTIVE: To observe heroin cue-induced changes of cerebral functional magnetic
      resonance images (fMRI) and the effect of acupuncture of Zusanli (ST 36) on them
      under craving state in heroin-addicted volunteers. METHODS: Fourteen male
      volunteer heroin addicts were recruited in the present study. Brain images were
      acquired before, during (2 min) and after visualizing heroin (placed in a
      transparent glass mug) and acupuncture of Zusanli (ST 36) on a 1.5-T Siemens
      Symphony MRI system equipped with a standard head coil. Acupuncture stimulation
      was applied to bilateral Zusanli (ST 36) by manipulating a filiform needle at a
      frequency of about 60 cycles/min and an angle of about 180 degrees for 2 min. The
      acquired neuroimaging data were analyzed by AlphaSim, AFNI. RESULTS: During
      heroin-visual stimulation, the markedly activated brain areas (increase of blood
      oxygen level-dependent signal) of fMRI were bilateral middle frontal gyrus, left
      cingulate gyrus, bilateral insula, occipital cortex, left cuneus, cerebellum,
      bilateral thalamus, right hippocampus and right amygdala etc. which are closely
      related to the human's craving psychological activities. When acupuncture given,
      meaning processing stronger sensory task, the heroin-addicted subjects showed
      apparent activation of the brain areas including the right anterior cingulate
      gyrus, right insula, thalamus, right hippocampal gyrus etc. which activation
      degrees were significant lower than those of heroin related visual stimulation.
      CONCLUSION: Acupuncture of Zusanli (ST 36) can lessen heroin cue-induced
      activation degree of the brain areas involving psychological craving, suggesting
      that acupuncture is able to suppress the heroin addiction patients' drug abuse
      craving.

PMID- 21717781
TI  - [Randomized controlled clinical trials for acupuncture treatment of aura-absence
      migraine patients].
AB  - OBJECTIVE: To observe the therapeutic effect of acupuncture therapy for aura
      absence migraine. METHODS: A total of 60 aura-absence migraine outpatients who
      signed an informed consent participated in the present study. They were
      randomized into medication group and acupuncture group (n = 30/group) according
      to a randomized number table and their visiting sequence. Patients of acupuncture
      group were treated by acupuncture of Ashi-point, Baihui (GV 20), Taiyang (EX-HN
      5), Shuaigu (GB 8), Fengchi (GB 20), Benshen (GB 13) and Lieque (LU 7). The
      acupuncture needles were retained for 30 min after "Deqi", and the treatment was
      conducted once daily, 6 times every week and continuously for 4 weeks. Patients
      of the medication group were treated with oral administration of Flunarizine (10
      mg/time, once every night) for 4 weeks. The SF-36 Quality-of-Life Instrument (SF
      36) and integral scores of headache were measured before and after the treatment.
      RESULTS: In comparison with the pre-treatment, scores of physical functioning
      (PF), role-physical (RP), bodily pain (BP), social functioning (SF), role
      emotional (RE), vitality (VT), mental-health (MH) and general health (GH) of SF
      36 in both medication and acupuncture groups were increased significantly (P <
      0.05), and those of PF, RP and BP of the acupuncture group were significantly
      higher than the scores of the medication group (P < 0.05). The integral scores of
      headache were decreased significantly in both medication group and acupuncture
      group (P < 0.05), and those of the acupuncture group were remarkably lower than
      the scores of the medication group after the treatment (P < 0.05). Of the two 30
      migraine patients in the medication and acupuncture groups, 1 (3.33%) and 9
      (30.00%) were cured, 1 (3.33%) and 2 (6.67%) had a marked improvement in their
      symptoms, 9 (30.00%) and 8 (26.67%) were effective, 19 (63. 33%) and 11 (36.67%)
      were ineffective, with the total effective rates being 36.67% and 63.33%,
      respectively. The cure rate and the total effective rate of the acupuncture group
      were significantly higher than those of the medication group (P < 0.05).
      CONCLUSION: Acupuncture therapy can raise the migraineurs' life quality, lessen
      the times and severity of headache attack, and its therapeutic effect is superior
      to that of medication.

PMID- 21717782
TI  - [Comparison of cutaneous temperature at 12 Jing-well points regions of bilateral
      yin- and yang-meridians in healthy volunteers].
AB  - OBJECTIVE: To observe differences of cutaneous temperature of the 12 Jing-well
      points regions of the yin-meridians and yang-meridians, and on the upper and
      lower limbs so as to provide a reference for clinical diagnosis. METHODS: A total
      of 26 healthy young volunteers (15 men and 11 women, 23 to 31 years in age)
      participated in the present study. The skin temperature of the 12 Jing-well
      points [Shaoshang (LU 11), Sahngyang (LI 1), Yinbai (SP 1), Lidui(ST45),
      Shaochong (HT9), Shaoze (SI 1), Yongquan (KI 1), Zhiyin (BL 67), Zhongchong (PC
      9), Guanchong(SJ 1), Dadun (LR 1) and Qiaoyin (GB 44)] at night (19:00-21:00) was
      detected under a room temperature of (20 +/- 2) degrees C and humidity of 65%-75%
      by using an infrared thermometer. RESULTS: Comparison between the single Jing
      well point of the yin-meridians and that of the yang-meridians showed that only
      the cutaneous temperature of Zhiyin (BL 67) was significantly lower than that of
      Yongquan (KI 1, P < 0.05). No significant differences were found between
      Shaoshang (LU 11) and Shangyang (LI 1), Yinbai (SP 1) and Lidui (ST 45), Shao
      chong (HT 9) and Shaoze (SI 1), Zhongchong (PC 9) and Guanchong (SJ 1), and
      between Dadun (LR 1) and Qiaoyin (GB 44) in the skin temperature (P > 0.05).
      Comparison between the 6 Jing-well points of the 6 yin-meridians group and those
      of the 6 yang-meridians group showed that the average skin temperature of the
      latter was significantly lower than that of the former (P < 0.01). The average
      skin temperature was significantly lower at the 3 Jing-well points of the 3 yin
      meridians of foot than that at the 3 Jing-well points of the 3 yin-meridians of
      hand (P < 0.01). Such is the case at the 3 Jing-well points of the 3 yang
      meridians of foot in comparison with the 3 yang-meridians of hand (P < 0.01). The
      average skin temperature of the 6 Jing-well points of the right yang-meridians
      was significantly higher than that of the 6 Jing-well points of the left yang
      meridians (P < 0.01). No significant differences were found between the left yin
      meridians and right yin-meridians in skin temperature (P > 0.05). CONCLUSION: The
      average skin temperature values of the Jing-well points are evidently higher at
      the 6 yin-meridians than at the 6 yang-meridians, obviously higher on the upper
      limbs than on the lower limbs, and apparently higher on the right meridians than
      on the left meridians in healthy volunteers.

PMID- 21717783
TI  - [A systematic review of randomized controlled clinical trials of abdominal
      acupuncture treatment of cervical spondylosis].
AB  - OBJECTIVE: To assess the effect and methodological quality of clinically
      randomized controlled studies on abdominal acupuncture therapy for cervical
      spondylosis and to make out its current situation, validity and applicability.
      METHODS: Using the PubMed, CNKI (China Academic Journals Full-text Database), VIP
      (VIP Chinese Science and Technology Periodicals Database) and Wanfang Digital
      Periodicals Electronic Database covering the period of 1989-2009, we did a
      literature search on the original articles of abdominal acupuncture treatment of
      cervical spondylosis and selected those accorded with the standards of randomized
      controlled studies. Animal studies, surveys, and news articles, and those
      duplicated, being absent in diagnostic criteria and non-randomized controlled
      trials were excluded. The papers' quality was analyzed by using the Jadad quality
      assessment scoring system and the therapeutic effect evaluated by using Review
      Manage 4.2.7 software. RESULTS: A total of 8 papers containing 909 cervical
      spondylosis patients and written in Chinese were included. These 8 studies used
      the effective rate as the primary outcome, 2 of them used the McGill Pain
      Questionnaire scales at the same time. Meta-analysis showed that the abdominal
      acupuncture group was better than the control group in visual analogue scale
      score (P < 0.05). No significant differences were found between abdominal
      acupuncture and routine acupuncture [OR = 3.29, 95% CI (0.13, 82.99)], EA [OR =
      2.09, 95% CI (0.36, 11.95)] and traction therapy [OR = 6.06, 95% CI (3.01,
      12.18)] in the total effective rate, pain rating index score [WMD = -2.24, 95% CI
      (-5.29, 0.81)] and the present pain intensity score [WMD = -0.84, 95% CI (-2.13,
      0.44)]. CONCLUSION: At the present, there has been no sufficient evidence to
      ensure that in the treatment of cervical spondylosis, the abdominal acupuncture
      therapy is superior to routine acupuncture, EA and traction therapy. Attention
      should be paid to the randomized controlled study of larger samples and qualified
      design.

PMID- 21717784
TI  - [Progress of researches on mechanism of acupuncture therapy underlying
      improvement of acute cerebral hemorrhage].
AB  - In the present paper, the authors review the progress of researches on the
      mechanism of acupuncture therapy underlying improvement of acute cerebral
      hemorrhage from experimental studies and research methods. The effects of
      acupuncture intervention mainly involve (1) lessening inflammatory reactions, (2)
      reducing impairment of free radicals and excitatory amino acids on cerebral
      neurons, (3) balancing release of vascular bioactive substances to increase
      regional cerebral blood flow, and (4) promoting repair and regeneration of the
      neural tissue, etc. In regard to the research methods, many new biological
      techniques such as biological molecular approaches, neuro-cellular chemical
      methods, reverse transcription-polymerase chain reaction (RT-PCR) or quantitative
      real time-PCR, situ hybridization, western blotting, electron microscope, etc.,
      have been extensively applied to researches on the underlying mechanism of
      acupuncture therapy for cerebral infarction. In addition, the authors also
      pointed out that in spite of achieving some bigger progresses in experimental
      studies, most of the results basically reflect static, isolated and regional
      changes rather than dynamic and whole body changes. For this reason, more vivo
      research techniques and noninvasive research methods are highly recommended to be
      used in the future research on the underlying mechanisms of acupuncture therapy
      for acute cerebral ischemia.

PMID- 21717785
TI  - [Progress of studies on effects of acupuncture on cellular signal transduction].
AB  - In order to elucidate the underlying mechanism of acupuncture in regulating
      different physiological functional activities at cellular level, abundant
      researches have been conducted on cellular signal transduction activities. The
      present article preliminarily analyzes acupuncture stimulation induced various
      cellular signaling pathways from the afferent physical signals of the regional
      mechanical stimulation at the acupoint, activation of receptors of the cellular
      membrane such as Guanine nucleotide binding protein coupled receptors, etc.,
      intracellular second messenger molecules including cAMP, Ca2+, inositol
      triphosphate, diacyl glycerol, etc., signal transduction pathways as mitogen
      activated protein kinase, Janus kinase-signal transduction and transcription
      activator, nitrogen oxide-cyclic guanylic acid, etc., to the extremely
      complicated cellular signal transduction networks. In addition, the present paper
      also makes a discussion on the present developing situation of acupuncture
      research. It is possible that the connective tissue of the body surface will
      become a key point in the future research on acupuncture remedy. More attention
      should be paid to the interrelation among various intracellular signaling
      pathways and the network of cellular signal transduction in the research on
      acupuncture therapy for regulating a variety of physiological effects.

PMID- 21717786
TI  - [Selenium and cancer: from prevention to treatment].
AB  - Selenium (Se) is an essential dietary component for all animals, including human
      beings, that is regarded as a protective agent against cancer. Although the mode
      of its anticancer action is not yet fully understood, several mechanisms, such as
      antioxidant protection through selenoenzymes, stimulation of DNA repair, and
      apoptosis in tumor prestages have all been proposed. Despite the unsupported
      results of the last "SELECT" trial, the cancer-preventing activity of Se has been
      demonstrated in a majority of epidemiological studies. Moreover, recent studies
      suggest that Se has a potential to be used not only in cancer prevention but also
      in cancer treatment, where in combination with other anticancer drugs or
      radiation it may increase the efficacy of cancer therapy. In combating cancer
      cells, Se acts as a prooxidant rather than an antioxidant, inducing apoptosis
      through the generation of oxidative stress. Thus, inorganic Se compounds, having
      high redox potency, represent a promising option in cancer therapy.

PMID- 21717787
TI  - [High-dose interferon alpha in treatment of patients with malignant melanoma,
      monitoring of predictive and prognostic biomarkers].
AB  - BACKGROUNDS: The incidence of malignant melanoma is increasing by about 2-5% per
      year, exceeding an incidence of all other tumors. Adjuvant immunotherapy with
      high-dose interferon (HDI) as per the ECOG 1684 trial Kirkwood's schema is still
      recommended as a standard. HDI should be started within 60 days after a surgical
      procedure. Meaningful adjuvant immunotherapy is based on radical surgical
      excision, an investigation of the sentinel node and regional lymph node
      dissection, if indicated. Current research aims to utilize routinely usable
      biomarkers in order to define patients who would explicitly profit from HDI.
      DESIGN: The authors present a review of HDI trials, focusing on the management of
      adverse effects of HDI and on biomarkers. This review also discusses the initial
      own experiences at the Oncology Centre in Hradec Kralove. CONCLUSION: Malignant
      melanoma is a very immunogenic tumour. Immunotherapy with HDI is considered to be
      the only therapeutic modality so far that has been proven to prolong relapse-free
      survival and overall survival (in short-time criterion) in adjuvant setting.
      However, the results of these trials are inconsistent and particular biomarkers
      of therapeutic response have not been defined yet.

PMID- 21717788
TI  - [Gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumours (GISTs) are the most common group of mesenchymal
      tumours affecting the gastrointestinal tract. Despite this, GISTs are relatively
      rare, since all mesenchymal tumours constitute just 1 percent of all primary GI
      cancers. Most often, GISTs affect the stomach and proximal small intestine but
      can be found in any section of the alimentary tract, including, occasionally, the
      omentum, mesentery and peritoneum. Virtually all GISTs (especially those larger
      than 1 cm) have malignant potential. Malignant potential of a tumour increases
      with its size and its mitotic rate, and it also depends on its anatomic location:
      intestinal GISTs are more aggressive than gastric tumours. Treatment of GISTs was
      revolutionized when it was discovered that mutational activation of KIT or PDGFRA
      stimulates the growth of these cancer cells. Mutational activation of KIT or
      PDGFRA led to abnormal activation of receptor tyrosine kinase and uncontrolled
      oncogenic signalling. This uncontrolled oncogenic signalling can be specifically
      targeted therapeutically with small molecule inhibitors of the receptor tyrosine
      kinase (imatinib, sunitinib). All GISTs > or = 2 cm in size should be resected.
      To reduce disease recurrence, adjuvant imatinib therapy is recommended for all
      high-risk patients after resection. Neoadjuvant therapy is recommended for
      primarily unresectable tumours or a limited amount of potentially resectable
      metastatic disease. The goal of treatment is to reduce tumour size, thus
      facilitating complete surgical resection and increasing the likelihood of organ
      preservation.

PMID- 21717789
TI  - [The dynamics of psychosocial burden development in breast cancer survivors:
      clinical success with psychosocial consequences].
AB  - BACKGROUNDS: Modified radical mastectomy (MRM) and breast-conserving surgery
      (lumpectomy, quadrantectomy - BCS) have shown equivalent clinical outcome in
      early stage breast cancer. On the other hand, quality of life and, probably,
      survival time of these patients are negatively influenced by fear of cancer
      recurrence, leading to episodes of anxiety, depression, and frustration, and,
      subsequently, physical, marital, sexual, and social functioning disorders. The
      aim of the present study was to analyze the dynamics and qualitative changes in
      psychosocial morbidity outcomes in breast cancer survivors one and three years
      after MRM versus BCS. METHODS: A survey evaluating psychosocial morbidity of
      patients was performed by distributing Slovak version of the standardised EORTC
      QLQ.C30:3 and EORTC-QLQ-BR23 questionnaires provided by the European Organisation
      for Research and Treatment of Cancer. The survey was performed in both arms of
      breast cancer patients surviving one and three years after MRM versus BCS.
      RESULTS: Patients surviving one year post MRM or BCS scored their quality of life
      rather low (2-4, very bad - acceptable), while 78% patients surviving three years
      after BSC scored considerably higher (5-6, good - very good). However, 22% of
      patients in this arm considered their quality of life bad, scoring comparably
      with patients in the MRM arm. While psychosocial burden and behavioural risk
      profile remain fully expressed in MRM-treated breast cancer patients three years
      post surgery, the patients surviving three years after BCS suffer from
      significant emotional dysfunction. CONCLUSION: The shift in the quality and
      intensity of psychosocial dysfunction symptoms in breast cancer patients
      surviving three years after BCS requires greater attention related to the need
      for appropriate community-based psychosocial interventions and psychosocial
      prevention due to the negative impact of continuing and even accelerated
      psychosocial distress on the quality of life of surviving patients and remission
      period of the malignant disease.

PMID- 21717790
TI  - [Radiofrequency ablation of pancreatic neuroendocrine tumor].
AB  - BACKGROUNDS: Pancreatic neuroendocrine tumors (PNETs) include a broad range of
      neoplasms spanning from relatively benign to malignant. Radical resection has
      been advocated as the only curative method. Debulking (R2) resection can be
      indicated for locally unresectable PNETs. Debulking surgery improves the quality
      of life and prolongs overall survival. The disadvantages of this approach include
      bleeding, pancreatic fistula and tumor spread. No alternative method that would
      eliminate these complications has been published yet. Considering the encouraging
      results of the studies describing radiofrequency ablation (RFA) of locally
      advanced pancreatic cancer, a question arises, whether it might be possible to
      use RFA as a R2 resection alternative in PNETs. CASE: A 73-year-old gentleman had
      been admitted due to abdominal pain and hyperglycaemic syndrome. Contrast
      enhanced CT showed a tumor of pancreatic head invading portal vein (PV) and
      superior mesenteric vein (VMS). A surgery was indicated on the basis of EUS
      guided FNAB that verified a PNET of uncertain biological behaviour. The surgery
      confirmed a locally advanced tumor of pancreatic head invading the PV and SMV.
      Due to the polymorbidity, radical pancreatoduodenectomy with SMV resection was
      not indicated. Because of the presence of symptoms, RFA of the PNET using
      ValleyLab generator with cooltip cluster electrode, was performed. Postoperative
      course was uneventful. Final immunohistochemical examination verified a well
      differentiated grade 1 PNET. The patient was regularly monitored during a three
      year follow-up. The quality of life was evaluated using standardized EORT QLQ-30
      questionnaire. Pain was assessed by a ten-point visual analogue scale (VAS).
      Ablated area was evaluated annually by contrast-enhanced CT. Postoperatively,
      abdominal pain ceased (pain decrease from 2 to 0 on VAS). Insulin dose was
      reduced from 46 IU (international units) to 20 IU of Humulin-R per day. CT
      verified tumor regression according to RECIST (response evaluation criteria in
      solid tumors). During the three-year follow-up, no local progression or tumor
      dissemination was observed. CONCLUSION: We present the first case report of a
      patient with locally advanced symptomatic pancreatic neuroendocrine tumor
      successfully treated by intraoperative radiofrequency ablation. More clinical
      studies are needed to evaluate the clinical relevance of this cytoreductive
      method in the PNET indication.

PMID- 21717791
TI  - [Regression of an osteolytic lesion in a patient with multiple myeloma treated
      with clodronate after a successful therapy with bortezomib-based regimen].
AB  - BACKGROUNDS: Osteolytic lesions are a common manifestation of multiple myeloma,
      though their healing is rare in these patients. Generally, during a complete
      remission, lesions only stop progressing; radiologically evident recalcification
      is exceptional. CASE: Herein we report a case of a male patient born in 1941 and
      diagnosed in 2005 with IgA multiple myeloma presenting with multiple osteolytic
      bone lesions. Administration of 4 cycles of VAD chemotherapy (vincristine,
      adriamycin, dexamethasone) with subsequent autologous peripheral blood stem cell
      transplantation and maintenance treatment with interferon alpha had resulted into
      a very good partial remission. In 2009, the disease relapsed with enlargement of
      osteolytic lesions evident on skiagrams. The largest lesion, reaching 24 x 10 mm
      in size, was located in the left femur. A complete remission of the disease was
      achieved with CVD senior regimen (cyclophosphamide, bortezomib, dexamethasone, 8
      cycles in total). Bisphosphonates (zoledronate, ibandronate and, from 2007,
      clodronate) were administered as a long-term supportive therapy. A one-year
      follow-up skiagram of the left femur revealed over 50% regression of the
      osteolytic lesion (10 x 5 mm) documented in a set of pictures herein. CONCLUSION:
      A complete remission of the disease after an administration of bortezomib
      (Velcade)-based regimen in a long-term clodronate (Bonefos)-treated patient with
      relapsed multiple myeloma is radiographically apparent by clear healing signs of
      the osteolytic bone lesion.

PMID- 21717792
TI  - [Can cancer patient in terminal stage of cancer die with dignity at home? And
      under what conditions?].
AB  - In their brief communication, the authors are discussing the issue of palliative
      care for cancer patients in terminal stage of cancer. The authors are also
      contributing their own experience with the provision of such care to patients who
      wish to die at home.

PMID- 21717794
TI  - [Palliative care in the Czech Republic 2011--some notes].

PMID- 21717793
TI  - [Radiotherapy and the flow of data and documentation].
AB  - Working approaches to radiotherapy are constantly in contact with new techniques
      that simultaneously require more advanced information flow and integration of all
      required information. These procedures are multi-dimensional and comprise a broad
      spectrum of documentation (patient demography, radiotherapy data, information
      required for diagnosis and treatment specification, illustrative records, etc.).
      These data are indispensable to the patient treatment process and it is crucial
      that they be integrated into patient health documentation. They are also
      necessary to enable long-term and speedy access to the data fields required by
      staff involved in treatment. In view of the various requirements placed on
      systems and their range of usage, it is essential that communication standards
      (DICOM, DICOM RT, PACS, HL7) are employed in such a way as to ensure
      compatibility and common systems communication.

PMID- 21717795
TI  - [Chronic obstructive pulmonary disease and asystole].

PMID- 21717796
TI  - Abstracts of the Meeting of the Associazione Italiana Sistema Nervoso Periferico.
      April 28-30, 2011. Bologna, Italy.

PMID- 21717797
TI  - Abstracts of the Health Services Research & Pharmacy Practice Conference.
      Norwich, United Kingdom. May 5-6, 2011.

PMID- 21717798
TI  - The doomsday strain: can Nathan Wolfe thwart the next AIDS before it spreads?

PMID- 21717799
TI  - Mother courage: a family tragedy and a scientific crusade.

PMID- 21717800
TI  - We have no bananas: can scientists defeat a devastating blight?

PMID- 21717801
TI  - Meet Dr. Freud: does psychoanalysis have a future in an authoritarian state?

PMID- 21717802
TI  - The hot spotters: can we lower medical costs by giving the neediest patients
      better care?

PMID- 21717803
TI  - [one hundred books which built up neurology (52)--Hermann von Helmholtz "Die
      Lehre von den Tonempfindungen als physiologische Grundlage fur die Theorie der
      Musik" (1863)].

PMID- 21717804
TI  - DNA repair: a key mechanism stabilizing the genome.

PMID- 21717805
TI  - Mitochondrial DNA mutations in patients with HRHPV-related cervical lesions.
AB  - High risk human papillomaviruses (hr-HPV) are known to be the etiological agents
      of cervical cancer disease. On the other hand, other cofactors are considered to
      be important in cervix carcinogenesis. Mutations in mitochondrial DNA (mtDNA) as
      well as alterations in mtDNA content have been reported in numerous cancers
      examined to date. The D-loop region has been shown to be a mutational "hot spot"
      in human cancer. In order to evaluate the role of mtDNA mutations in cervical
      lesions progression, cervical specimens (from 79 women, 29-65 years old) were
      investigated. DNA was isolated (High Pure PCR Template, Roche Diagnostics) from
      cervical cells from patients with different cytology (normal cervical epithelium,
      ASCUS-Atypical Squamous Cells of Undetermined Significance, LGSIL-Low-Grade
      Intraepithelial Lesion, HGSIL-High-Grade Intraepithelial Lesion and SCC-Squamous
      Cell Carcinoma) and tested for HPV DNA presence (Linear Array HPV Genotyping
      Test, Roche Diagnostics). To elucidate a causative role of mtDNA in cervical
      lesions, mtDNA mutations were investigated using Mutector mtDNA kit (TrimGen
      Corporation). In patients with normal and ASCUS cytology, mtDNA mutations were
      absent. 16.66% of LGSIL patients presented mutations in D-loop region whereas
      28.57% HGSIL cases showed mutations in mtDNA. Mutations were detected in 66.66%
      cases of SCC cases. These studies provide strong evidence that instability in the
      D-loop region of mtDNA may be involved in cervical dysplasia. We suggested that
      mtDNA mutations may play a role in cervical precursor lesions and cancer but
      their role in the mechanism of carcinogenesis remains to be solved.

PMID- 21717806
TI  - In vitro antimicrobial activity of Romanian medicinal plants hydroalcoholic
      extracts on planktonic and adhered cells.
AB  - The aim of this study was to assess the antibacterial and antifungal potential of
      some Romanian medicinal plants, arnica--Arnica montana, wormwood--Artemisia
      absinthium and nettle--Urtica dioica. In order to perform this antimicrobial
      screening, we obtained the vegetal extracts and we tested them on a series of
      Gram-positive and Gram-negative bacteria, and also against two fungal strains.
      The vegetal extracts showed antimicrobial activity preferentially directed
      against the planktonic fungal and bacterial growth, while the effect against
      biofilm formation and development was demonstrated only against S. aureus and C.
      albicans. Our in vitro assays indicate that the studied plant extracts are a
      significant source of natural alternatives to antimicrobial therapy, thus
      avoiding antibiotic therapy, the use of which has become excessive in recent
      years.

PMID- 21717807
TI  - Assessing the efficiency of free light chain assay in monitoring patients with
      multiple myeloma before and after autologous stem cell transplantation along with
      serum protein electrophoresis and serum protein immunofixation.
AB  - Monoclonal gammopathies are a group of disorders, referred to as
      paraproteinaemias, dysproteinaemias or immunoglobulinopathies, associated with
      monoclonal proliferation of plasma cells. Monoclonal immunoglobulin secreted by
      these cells is an indicator of clonal proliferation. The aim of this study is to
      analyze the efficiency of three methods: serum protein electrophoresis (SPE),
      serum protein immunofixation (IFE) and FLC (free light chain) assay for the
      diagnosis and monitoring of the tumor burden in multiple myeloma. In this study
      we have presented the dynamic evolution of 7 patients with intact immunoglobulin
      multiple myeloma (IIMM) (2 IgG, kapa; 3 IgG, lambda; 1 IgA, kappa; 1 IgA, lambda)
      and 2 patients with light chain multiple myeloma before and after autologous
      peripheral blood stem cell transplantation (PBSCT). All 7 patients fulfilled the
      four criteria for the diagnosis of IIMM: bone marrow plasma cells exceeding 20%,
      lytic bone lesions, identification and quantification of M protein by scanning
      densitometry of electrophoresis gels, IFE (immunofixation protein
      electrophoresis) confirmed and typed the M protein. All patients had been given
      cytotoxic chemotherapy (VAD or VELCADE) before autologous (PBSCT). In two of the
      patients with IIMM both SPE and kappa/lambda ratio fell towards normal range
      after autologous PBSC and both reported a relapse of the disease after 23 months
      and 19 months respectively. SPE could not normalize after chemotherapy and
      transplantation in three patients with IIMM, the kappa/lambda ratio being the
      only marker used to monitor the tumor kill. In one patient the kappa/lambda ratio
      could not normalize even after PBSCT still indicating the presence of plasma cell
      disorder at the time when IFE was still negative. 16 months after PBSCT both SPE
      and FLC indicated a relapse of the disease. Classical SPE failed to demonstrate
      the presence of M-protein in light chain multiple myeloma, the diagnosis being
      established by using IFE and the FLC assay. Because IFE is a qualitative method
      and its interpretation may be sometimes subjective, FLC was the only method used
      to follow the disease course. The measurement of kappa/lambda ratio proved to be
      more sensitive than SPE, IFE and the levels of free light chains kappa or lambda
      individually indicating whether the treatment is effective or not.

PMID- 21717808
TI  - Immunodetection of added glycomacropeptide in milk formulas and milk powders.
AB  - The present study aimed the detection of fraudulent manipulation of milk powder
      with a low cost component--whey powder, by applying the immunochromatographic
      assay to identify glycomacropeptide. Five commercial milk powder samples of
      various brands from the national market were analyzed: lactose enriched milk
      powder type 26, two whole milk powders, vitamin enriched milk powder and full
      cream milk powder. Our results showed additional whey (1-2%) in 60% of the
      selected samples after casein removal by precipitation with 20% trichloracetic
      acid. Another investigated sample--the enriched UHT milk for children aged 4-12
      years--proved addition of whey. Other two commercial toddler formula milk powder
      samples of different brands were used for comparison for the presence of
      glycomacropeptide. The first sample which was regularly labeled as containing
      whey protein concentrate was found positive for glycomacropeptide in accordance
      with the label information, while the second one not containing whey proteins as
      specified by the product label, was found negative for glycomacropeptide, these
      two samples being in accordance with the actual legislation.

PMID- 21717809
TI  - Bacterial extract cantastim activates macrophages via TLR-2.
AB  - CANTASTIM is a second generation bacterial immunomodulator. The aim of this study
      was to examine the mechanism by which bacterial immunomodulator CANTASTIM induces
      production of inflammatory cytokines in monocytes/macrophages. Proinflammatory
      cytokines were induced in PMA-differentiated THP-1 cells by stimulation with TLR
      agonists and CANTASTIM in the presence or absence of anti-TLR blocking antibodies
      or isotype matched control antibodies. Also, RNA interference was used to
      knockdown TLR2 or TLR4 expression in PMA-differentiated THP-1 cells before
      stimulation. As expected, induction of TNF-alpha and IL-6 by TLR4 agonist LPS was
      inhibited in a significant manner by anti-TLR4 but not by anti-TLR2 antibody.
      Unexpectedly, treatment with anti-LR2 blocking antibody inhibited only IL-6
      production induced by Pam3CSK4 while the level of TNF-alpha was unchanged. When
      cells were stimulated by TLR2 agonist heat-killed Listeria monocytogenes the
      release of TNF-alpha was significantly attenuated by anti-TLR2 antibodies.
      Silencing of TLR2 led to a statistically significant inhibition of TNF-alpha
      secretion induced by TLR2 agonist while siRNA silencing of TLR4 did not affect
      the response to TLR2 agonist. Cells exposed to CANTASTIM produced significant
      levels of pro-inflammatory cytokines but the levels were lower than LPS
      stimulated cells. Production of both cytokines was inhibited by treatment with
      anti-TLR2 blocking antibody and not by anti-TLR4 antibody. Silencing of TLR2 led
      to a statistically significant inhibition of TNF-a secretion induced by CANTASTIM
      while silencing of TLR4 had no effect on the response to CANTASTIM. These results
      support the hypothesis that CANTASTIM may exert its immunomodulatory and adjuvant
      activities through interaction of its bacterial components with TLR2.

PMID- 21717810
TI  - Implant microparticles--a new concept for non-invasive cancer therapy.
AB  - Some progress in cancer research was possible in recent years mainly due to
      important advances in nanotechnology. However, clinical use of nanomaterials is
      still hindered by limitations. In search of better performance and control of
      inoculated materials, the efficiency and toxicity of SBBC implant particles was
      assessed. B16 tumoral cells (murine melanoma) were subjected to SBCC particles
      using in vitro and in vivo experimental models. In vitro experiments concerning
      the growth inhibition of tumoral cells using SBCC particles were performed by
      Flow Cytometry and by MTT Assay. In vivo experimental model (C57BL/6 mice) was
      used to complete this investigation: weight, viability and tumoral dimension were
      monitored. An anti-proliferative activity on B16 tumoral cells and an ability to
      produce apoptosis were observed. A reduction of tumoral volume and a 54% survival
      rate in the treated animals compared to the controls was obtained. Our
      preliminary results showed that the SBCC implants were effective against B16
      melanoma cells, while there is no toxicity associated.

PMID- 21717811
TI  - The influential role of genes in obesity.
AB  - Obesity risk is amplified in the presence of obese relatives yet does not usually
      follow classic Mendelian inheritance patterns. A combination of gene mutations,
      deletions and single nucleotide polymorphisms are all known to contribute to
      obesity. Most cases are polygenic, the result of multiple genes interacting with
      a changing environment. Each "obesity gene" only makes a small contribution to
      phenotype, but collectively, inherited genetic variations play a major role in
      determining body mass and how the body responds to physical activity and
      nutrition. While obesity is most commonly associated with polygenic inheritance,
      there are other instances in which the cause is monogenic or syndromic. Monogenic
      obesity typically is caused by a single gene mutation with severe obesity as the
      main symptom. Syndromic obesity, on the other hand, has many characteristics, of
      which obesity is one symptom.

PMID- 21717812
TI  - Dysfunctional hormonal regulation of metabolism in obesity.
AB  - A complex network of hormones from the pancreas, adipose tissue, stomach,
      intestines and the central nervous system coordinates regulation of metabolism
      and energy balance. Obesity disrupts this regulatory network. This paper reviews
      the anorexigenic and orexigenic hormones and their dysfunctional regulation in
      obesity.

PMID- 21717813
TI  - Insulin resistance, obesity and the metabolic syndrome.
AB  - The metabolic syndrome is a clinically important but often misunderstood topic. A
      concept in evolution, controversy surrounds the metabolic syndrome. The medical
      literature documents disagreement in the criteria for diagnosis, a shift in
      emphasis as to the roles of obesity and insulin resistance as underlying causes,
      and questions about the fundamental clinical utility of the syndrome. The
      practical strengths and limitations of the metabolic syndrome in clinical
      practice are reviewed.

PMID- 21717814
TI  - Sleep apnea and obesity.
AB  - The dramatic increase in the worldwide prevalence of obesity has paralleled the
      increase in the prevalence of obstructive sleep apnea (OSA). Even with heightened
      awareness by the lay and medical communities, OSA is still markedly under
      diagnosed, as evidenced by the persistent presentation of late-stage
      cardiovascular complications in obese individuals newly diagnosed with sleep
      apnea. The clinical sequela of untreated and poorly-treated sleep apnea include
      conditions that are considered components of the metabolic syndrome for which
      central obesity is one of the major case-defining features. Hence, in this review
      of obesity and sleep apnea, it is unavoidable to include discussion of sleep
      apnea and other components of the metabolic syndrome. Proponents of this clinical
      perspective suggest that there are mutual genetic determinants that give rise to
      common phenotypic features and allow clustering of sleep apnea with the other
      components of the metabolic syndrome. Perhaps, the strongest observational
      evidence to support a link between sleep apnea and obesity is the similarity in
      age distribution of symptomatic sleep apnea and metabolic syndrome. The putative
      causal links between sleep apnea and each individual component of the metabolic
      syndrome have been extensively evaluated and have implicated bidirectional
      causality in certain metabolic conditions, such as obesity and sleep apnea, sleep
      apnea and diabetes mellitus, and obesity and diabetes mellitus. These studies
      collectively suggest that even modest weight loss improves OSA, and positively
      affects both metabolic and cardiovascular risk profiles.

PMID- 21717815
TI  - Obesity and cardiovascular disease.

PMID- 21717816
TI  - Behavioral and medical management of obesity.
AB  - South Dakota physicians are confronted by an epidemic of obesity. Developing an
      effective management strategy for patients with this condition can be daunting.
      This article reviews the evidence behind dietary, exercise-based, and
      pharmacological approaches to the care of the overweight and obese patient,
      offering recommendations to the clinician based on this evidence.

PMID- 21717817
TI  - An overview of the medical model for prevention, assessment and treatment of
      childhood obesity.
AB  - South Dakota physicians are confronted by an epidemic of obesity. Developing an
      effective management strategy for patients with this condition can be daunting.
      This article reviews the evidence behind dietary, exercise-based, and
      pharmacological approaches to the care of the overweight and obese patient,
      offering recommendations to the clinician based on this evidence.

PMID- 21717818
TI  - Childhood obesity and the emerging epidemic of type 2 diabetes.

PMID- 21717819
TI  - 5-2-1-0.

PMID- 21717820
TI  - Comparative effectiveness research: does the emperor have clothes?
AB  - With the recent allocation ofa $1.1 billion "down payment" to fund comparative
      effectiveness research (CER) from the American Recovery and Reinvestment Act of
      2009 (generally referred to as the stimulus package) and with $300 million being
      allocated for the Agency for Healthcare Research and Quality (AHRQ), $400 million
      for the National Institutes of Health, and $400 million for allocation at the
      discretion of the Secretary of Health and Human Services and with the National
      Center for Complementary Alternative Medicine putting out a request for research
      proposals for Comparative Effectiveness Studies of Complementary and Alternative
      Medicine, it is safe to say CER has entered a new era. CER solves two historical
      concerns for complementary and alternative medicine (CAM) researchers; first it
      focuses on effectiveness not efficacy; second it tests holistic approaches to
      care. Because it allows the providers to give care in any way they choose, it
      avoids the problem of reductionism inherent in standard random controlled trials.
      In CER, the provider can continue to practice holistically and to use
      individualized medicine to treat the patient. However, amid the largely positive
      responses to this move among researches in CAM, a more critical evaluation might
      be in order. This article argues that while the move to effectiveness research is
      a positive move for CAM, CER as currently being talked about and funded may just
      be a new form of privileging certain forms of evidence at the expense of other
      equally important and perhaps more relevant evidence.

PMID- 21717821
TI  - Anthroposophic medicine in pediatric primary care: a prospective, multicenter
      observational study on prescribing patterns.
AB  - BACKGROUND: Although the treatment of children has been a core domain
      ofanthroposophic medicine since its inception, a systematic analysis of
      anthroposophic therapies in pediatric primary care is still lacking. This study
      describes the spectrum of diagnoses and therapies observed in children treated in
      everyday anthroposophic practice. METHODS: Thirty-eight primary care physicians
      in Germany participated in this prospective, multicenter observational study on
      prescribing patterns. Prescriptions and diagnoses were reported for each
      consecutive patient. Multiple logistic regression analysis was used to determine
      factors associated with anthroposophic prescriptions. RESULTS: In 2005, a total
      of 57 893 prescriptions for 18 440 children under 12 years of age (48.1% female)
      were issued. In total, 50.3% of the prescriptions were classified as CAM remedies
      alone, 22.6% as conventional pharmaceuticals alone, and 27.1% as a combination of
      both. Anthroposophic remedies accounted for 41.8% of all medications prescribed.
      The odds ratio (OR) for receiving an anthroposophic remedy was significantly
      higher for the first consultation (OR= 1.19; confidence interval [CI]: 1.16
      1.23). Anthroposophic remedies were prescribed most frequently for disorders of
      the conjunctiva (OR = 2.47; CI: 2.27-2.70), otitis media (OR = 1.50; CI: 1.43
      1.59), acute upper respiratory tract infections (OR= 1.28; CI: 1.23-1.33), other
      respiratory diseases (OR= 1.15; CI: 1.07-1.24), digestive system and abdominal
      symptoms (OR= 1.39; CI: 1.28-1.51), general symptoms and signs (OR= 1.25; CI:
      1.16-1.36), .and pneumonia (OR= 1.36; CI: 1.25-1.49). The likelihood of being
      prescribed an anthroposophic remedy decreased with patient age (OR= 0.96; CI:
      0.95-0.96) and was lower in patients treated by a pediatrician (OR= 0.43; CI:
      0.42-0.44). Of the 2475 therapeutic procedures prescribed (29% anthroposophic),
      the most frequent were physiotherapy, speech therapy, ergotherapy, and
      logopedics. CONCLUSION: The present study is the first to provide a systematic
      overview of everyday anthroposophic medical practice in primary care for
      children. The findings show that practitioners of anthroposophic medicine take an
      integrative approach by combining conventional and anthroposophic treatments.

PMID- 21717822
TI  - Policosanol for managing human immunodeficiency virus-related dyslipidemia in a
      medically underserved population: a randomized, controlled clinical trial.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with
      dyslipidemia and increased risk for cardiovascular events; however, the use
      ofstatins in HIV-infected people is complicated by pharmacokinetic interactions
      and overlapping toxicities with antiretroviral medications. Policosanol is a
      dietary supplement derived from sugar cane that is widely used as a statin
      alternative in Latin America. PRIMARY STUDY OBJECTIVE: To collect feasibility
      data on sugar cane-derived policosanol to normalize dyslipidemic profiles in a
      sample of medically underserved HIV-infected people. METHODS/DESIGN: Randomized,
      controlled, double-blind clinical trial. SETTING: Two infectious disease
      outpatient clinics located in a Health Resources Service Administration
      designated medically underserved neighborhood in Chicago, Illinois. PARTICIPANTS:
      Fifty-four clinically stable HIV-infected people (91% black) with at least one
      lipid abnormality that warranted dietary modifications and/or drug therapy.
      INTERVENTION: Participants received either 20 mg/day of policosanol or placebo
      for 12 weeks, followed by a 4-week washout and crossover to the other arm.
      PRIMARY OUTCOME MEASURES: Efficacy measures included the standard lipid panel
      (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol,
      triglycerides) and nuclear magnetic resonance (NMR)-derived lipoprotein particle
      profiles. Safety measures included CD4+ T lymphocyte counts, plasma HIV
      ribonucleic acid levels, serum creatinine, and liver function tests. RESULTS:
      Policosanol supplementation was not associated with normalization of any
      dyslipidemic parameters as measured by the standard lipid panel or NMR
      spectroscopy-measured lipoprotein size or concentration. The supplement was well
      tolerated and was not associated with any changes in parameters of HIV disease
      progression. CONCLUSIONS: Our findings corroborate recent studies conducted
      outside Cuba that have failed to find any lipid modulatory effects for
      policosanol.

PMID- 21717823
TI  - A program consisting of a phytonutrient-rich medical food and an elimination diet
      ameliorated fibromyalgia symptoms and promoted toxic-element detoxification in a
      pilot trial.
AB  - BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become
      available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of
      a modified elimination diet and a supplemental medical food on clinical symptoms
      of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest
      Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ),
      metallothionein mRNA expression, and urinary toxic element excretion. METHODS:
      Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a
      sequential design. During the initial 4-week Program A (control), participants
      consumed a modified US Department of Agriculture food pyramid diet and a rice
      protein powder supplement that provided basic macronutrient support. During the
      second 4-week Program B (intervention), participants consumed a modified
      elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to
      baseline, both programs showed trends toward lower mean FIQ total score, MSQ
      total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest
      headaches score. Compared to Program A, Program B resulted in a significant
      decrease (P< .05) in the FIQpain score and stiffness score. Participants also had
      better pain tolerance at five tender points during Program B than during Program
      A. Higher metallothionein mRNA expression was observed during Program B. An
      increase in creatinine-adjusted mercury excretion and suggestive increase in
      creatinine-adjusted arsenic excretion were noted when Program B was compared to
      baseline. Urinary mercury/arsenic concentrations were inversely associated with
      FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and
      efficacious botanically derived medical food treatment program for the
      amelioration of FM symptoms.

PMID- 21717824
TI  - Chronic wound treatment with topical tea tree oil.

PMID- 21717825
TI  - Use of homeopathic injection therapy in treatment of Morton's neuroma.

PMID- 21717826
TI  - Development and classification of an operational definition of complementary and
      alternative medicine for the Cochrane collaboration.
AB  - During the past decade, the Cochrane Collaboration has been an increasingly
      important source of information on complementary and alternative medicine (CAM)
      therapies. From 2007 to 2008, the Cochrane CAM Field developed a topics list that
      allowed us to categorize all 396 Cochrane reviews related to CAM (as of The
      Cochrane Library, Issue 4, 2009). This topics list is an advance in making
      Cochrane reviews on CAM topics accessible to the public. In this article, we
      discuss challenges in developing the topics list, including developing an
      operational efinition of CAM, deciding which reviews should be included within
      the CAM Field's scope, developing the structured list of CAM Field-specific
      topics, and determining where in the topics list the reviews should be placed.
      Although aspects of our operational definition of CAM are open to revision, a
      standardized definition provides us with an objective, reproducible, and
      systematic method for defining and classifying CAM therapies.

PMID- 21717827
TI  - Bradly Jacobs, MD, MPH: changing the face of integrative medicine research.
      Interview by Craig Gustafson and Suzanne Snyder.

PMID- 21717828
TI  - Tapping the potential of research-based advocacy.

PMID- 21717829
TI  - Advocating for public health: does the real world matter?

PMID- 21717830
TI  - Sustaining an obesity prevention intervention in preschools.
AB  - ISSUE ADDRESSED: This paper outlines the healthy eating and physical activity
      strategies that were sustained over two and three years after a year-long
      preschool obesity prevention program in rural and regional NSW, Australia.
      METHODS: Seventeen preschool directors were interviewed as part of the pre and
      post-evaluation data collection in preschools in 2006 and 2007. In July 2009 a
      follow-up study of the Tooty Fruity Vegie program was conducted by an independent
      party to evaluate the program's sustainability. Research was in the form of a
      telephone interview and related to questions originally asked of the directors.
      RESULTS: Most of the Tooty Fruity Vegie strategies continued in preschools after
      health promotion contact ceased. The strategies that were sustained were those
      that involved experiential activities for the children (e.g taste testing and
      physical activity sessions), those that were easy for the preschool to implement
      (e.g. newsletter tips) and those that became embedded into the organisational or
      environmental framework (e.g. increased access to drinking water). CONCLUSION: A
      one-year multi-strategic obesity prevention program in preschool shows promise in
      sustaining some strategies beyond the year of assisted intervention.

PMID- 21717831
TI  - Support for smoke-free vocational education settings: an exploratory survey of
      staff behaviours, experiences and attitudes.
AB  - ISSUE ADDRESSED: TAFE staff are likely to play a pivotal role in achieving smoke
      free environments for vocational education.The aim of this survey was to explore
      staff experiences, behaviours and attitudes towards smoking and smoke-free
      policies for the TAFE setting. METHOD: A web-based survey that measured smoking
      behaviours, on-campus exposure to smoking, awareness of smoke-free policies and
      attitudes towards smoking and tobacco control was e-mailed to al staff at one
      TAFE New South Wales (NSW) institute. In total, 632 staff completed the survey.
      RESULTS: Overall, 10% of staff reported to be current daily, weekly or occasional
      smokers. Most staff (76.2%) said that they saw someone smoking at TAFE every day
      and the most common location was'outside buildings'(75.3%). A majority of staff
      (75.9%) said they avoided places at TAFE where they were exposed to other
      peoples'cigarette smoke. Only 26% said that existing smoking policies were always
      enforced. Non-smokers had a significantly higher (p<0.005) pro-tobacco control
      attitudes score mean of 4.2 (SD=1.8), compared with the mean of 2.3 (SD=1.4) for
      current smokers. Status as a non-smoker was the only statistically significant
      predictor of high pro-tobacco control attitude score. CONCLUSIONS: This study
      provides preliminary evidence that TAFE staff are likely to be supportive of
      smoke-free TAFE campuses.

PMID- 21717832
TI  - Reorienting a paediatric oral health service towards prevention: lessons from a
      qualitative study of dental professionals.
AB  - ISSUE ADDRESSED: Reorienting primary care dental services towards prevention is a
      priority for improving the oral health of Australian children with extensive
      dental caries. We explored the attitudes and beliefs of dental staff about the
      factors that helped or hindered the establishment and implementation of a
      hospital-based parent counselling program to manage existing, and prevent new,
      carious lesions in children. A further aim was to explore the influence of the
      program on the hospital's reorientation to prevention. METHODS: Eight of nine
      program staff participated in two focus group interviews, and two co-ordinating
      staff participated in semi-structured interviews. Interviews were audio-recorded
      and transcribed. Interview recordings and transcripts were analysed by
      qualitative thematic analysis. RESULTS: The participants identified a number of
      factors that they felt influenced the establishment and implementation of the
      program, including the dental team's support of the initiative, the advantages of
      building on existing clinic infrastructure and procedures, the utility of
      harnessing dental assistants as a resource for oral health promotion, and the
      confidence of dental professionals to provide parent counselling. CONCLUSION:
      Efforts to establish a preventive program in a public paediatric dental service
      should ensure that all members of the dental team are engaged during all phases
      of the program, that dental assistants are trained and supported to deliver
      parent counselling, and that interprofessional partnerships with services such as
      dietetics are fostered.

PMID- 21717833
TI  - Modifying the food supply at a community swimming pool: a case study.
AB  - ISSUE ADDRESSED: We report on a process evaluation of a project that aimed to
      replace energy-dense, nutrient-poor (EDNP) items at a community swimming pool
      kiosk. The analytic framework was the Analysis Grid for Environments Linked to
      Obesity (ANGELO). To contribute to health promotion practice in recreational
      settings, the process evaluation sought to determine the extent to which
      project'controversies' modified project objectives and strategies. METHODS: The
      case study method captured the project narrative. The primary data were
      interviews with key project participants, supplemented with project records and
      media articles.These were analysed thematically. RESULTS: The socio-cultural and
      political environments, particularly the capacity to exercise choice in relation
      to ENDP products, had considerable influence on the project. In the face of two
      controversies -"I thought everyone was signed up to it"and "We can't deny the
      kiddies their ice-cream" it was necessary for the project partners to modify the
      objectives and strategies and substantially change the target. CONCLUSIONS: The
      setting is highly responsive to both the micro and macro socio-cultural and
      political aspects of the environment.

PMID- 21717834
TI  - Culturally appropriate methods for enhancing the participation of Aboriginal
      Australians in health-promoting programs.
AB  - ISSUE ADDRESSED: This study investigated the application of an educational health
      promotion program, the Stanford Chronic Disease Self-Management Program (CDSM),
      within three Queensland Aboriginal (Murri) communities (rural, regional and
      urban). METHODS: A participant-observation approach was used and qualitative data
      was collected through interviews and focus groups. A total of 39 people
      participated, al of whom had been exposed to the program in different ways (i.e.
      leaders, health professionals, Elders who sponsored the program) during its
      recent deployment in their communities. RESULTS: Across all three regions,
      Aboriginal engagement in the program was found to be influenced by core factors
      that are well known and reflect our general understanding about Aboriginal
      history (e.g. the impact of negative medica interactions, the lack of cultural
      competence, the use of culturally insensitive methods of service delivery, the
      collectivity of Murri life and the holistic concept of health). However, a more
      important finding was that irrespective of these broad factors, the acceptability
      of the program in each community depended on the extent to which it had embraced
      and espoused several localised processes. The impact and nature of these
      processes differed across each region. CONCLUSIONS: Four local processes
      reflected the unique characteristics and profile of each community.They included
      the need to be responsive to local systems and structures, to incorporate local
      cultural traditions and knowledge bases, to use locally accepted forms of
      cultural communication, and to facilitate oca community participation and
      leadership in the program. Importantly, these factors determined the experience
      of the program within each community, ultimately influencing its acceptability,
      effectiveness and sustainability.

PMID- 21717835
TI  - Health literacy and Australian Indigenous peoples: an analysis of the role of
      language and worldview.
AB  - This article delineates specific issues relating to health literacy for
      Indigenous Australians. Drawing on the extensive experience of the authors' work
      with Yolnu people (of north-east Arnhem Land) and using one model for health
      literacy described in the international literature, various components of health
      literacy are explored, including fundamental literacy, scientific literacy,
      community literacy and cultural literacy. By matching these components to the
      characteristics of Yolnu people, the authors argue that language and worldview
      form an integral part of health education methodology when working with
      Indigenous people whose first language is not English and who do not have a
      biomedical worldview in their history. Only through acknowledging and actively
      engaging with these characteristics of Indigenous people can all aspects of
      health literacy be addressed and health empowerment be attained.

PMID- 21717836
TI  - Occupational sitting time: employees' perceptions of health risks and
      intervention strategies.
AB  - ISSUE ADDRESSED: There is increasing interest in the potential association
      between sedentary behaviour and poor health. This study examined office-based
      employees' perceptions of the health risks associated with prolonged sitting at
      work, and strategies to interrupt and reduce occupational sitting time. METHODS:
      Four focus groups were conducted with a convenience sample of Australian
      government personnel (20 women and two men). Open-ended questions concerning
      health risks and sitting reduction strategies were posed by lead researchers and
      focus group participants invited to express opinions, viewpoints and experiences.
      Audio recordings and summary notes of focus group discussions were reviewed by
      researchers to identify key response themes. RESULTS: Employees associated
      prolonged occupational sitting with poor health, primarily in terms of
      musculoskeletal issues, fatigue and de-motivation.This risk was seen as
      independent of physical activity. Workplace interventions tailored to
      occupational roles were viewed as important and considered to be the joint
      responsibility of individuals and organisations. Strategies included workload
      planning (interspersing sedentary and non-sedentary tasks), environmental change
      (e.g. stairwell access, printers away from desks), work tasks on the move (e.g.
      walking meetings) and purposive physical activity (e.g. periodic breaks,
      exercise/walking groups).The perception that these strategies would compromise
      productivity was identified as the primary barrier to implementation; team
      leaders were subsequently considered vital in enabling integration and acceptance
      of strategies into everyday workplace practices. CONCLUSIONS: Prolonged
      occupational sitting was perceived as detrimental to health. Suggested strategies
      targeted individuals, workplaces, organisations and environments.

PMID- 21717837
TI  - Workplace nutrition and physical activity promotion at Liverpool Hospital.
AB  - ISSUE ADDRESSED: The workplace is an effective way of reaching large numbers of
      adults during working hours, and increasing physical activity, promoting healthy
      eating or both.This paper evaluates the effectiveness of a workplace intervention
      in a hospital setting in Australia. METHODS: A 12-week program was conducted with
      399 employees of Liverpool Hospital, NSW, to increase physical activity and
      healthy eating. Participants received a pedometer, healthy cookbook, water
      bottle, sandwich container and Measure Up campaign resources. A web-based survey
      was completed at baseline and follow up. RESULTS: Sixty-six per cent of
      participants completed the follow-up survey. Those that did not complete the
      follow-up evaluation were not significantly different to completers. Respondents
      reported a significant increase in median minutes walked to 200 minutes and in
      vigorous physical activity to 85 minutes over the previous week. Participants
      consuming adequate fruit and vegetable per day increased by 24.7% and 22.7%,
      respectively. More participants also consumed breakfast on seven days of the week
      and consumed one or more litres of water per day. CONCLUSIONS: The intervention
      was successful for the participants. With some improvements to processes, we
      encourage further similar programs with the health sector workforce.

PMID- 21717838
TI  - Radio campaign to promote quality use of medicines among Italian, Mandarin and
      Cantonese speaking seniors in Australia.
AB  - ISSUE ADDRESSED: The objective of this study was to evaluate the effectiveness of
      a radio campaign in promoting the quality use of medicine (QUM) among Italian,
      Mandarin and Cantonese-speaking seniors. METHODS: One hundred and eight six in
      language radio advertisement spots and nine interviews were broadcasted during
      eight ethnic language radios programs in September and October 2008. Immediately
      before and after the campaign, telephone interviews were conducted with 1,200
      (600 before and 600 after) randomly selected Italian, Mandarin and Cantonese
      speaking seniors aged 50 or older. RESULTS: Awareness of QUM was increased by
      6%.The mean number of correct answers regarding QUM increased from 5.2 before the
      campaign to 5.7 after the campaign (p<0.001). The proportion of people who had
      correct answers to six or more questions (out of nine) increased by 12%
      (p<0.001). The increase was largest among the Cantonese-speaking seniors (27%),
      followed by the Mandarin (8%) and Italian seniors (4%, p<0.001). CONCLUSIONS: The
      radio campaign was effective in increasing awareness and knowledge of QUM among
      seniors. However, the effectiveness of the campaign varied between language
      groups.

PMID- 21717839
TI  - Motivating intentions to adopt risk-reducing behaviours for chronic diseases:
      impact of a public health tool for collecting family health histories.
AB  - ISSUES ADDRESSED: In the genomics era the use of valid and reliable tools for the
      collection of family health histories is proposed as a strategy for identifying
      those at higher risk of chronic disease and increasing the adoption of risk
      modifying behaviours.This study investigated the impact of a collection tool for
      a Family Health History Program in Western Australia upon uptake of key health
      messages and intentions to adopt risk-reducing behaviours for chronic diseases.
      METHODS: Initially a baseline population survey (n=1009) was undertaken to assess
      the collection of family health histories among adults and identify target
      populations for the tool. A targeted intercept survey (n=606) was then conducted
      with women to assess the tool. RESULTS: Around half the respondents indicated
      they were motivated to adopt one or more risk-reducing behaviours as a result of
      their exposure to the tool.The odds of being motivated to do something related to
      family health history were significantly greater for women who liked the too
      (AdjOR=3.1,95%Cl 2.1 4.5 ), thought it conveyed useful information (AdjOR=5.0,
      95%Cl 2.6-9.6), perceived family history to be more important than before they
      read the tool (AdjOR=3.4, 95%Cl 2.3-4.9) and had not previously collected family
      health history information (AdjOR=1.8, 95%Cl 1.1-3.0). CONCLUSION: At a whole-of
      population level most adults consider family health history important, but few
      have actually recorded this information. The tool raised awareness of the
      importance of family health histories to personal health and was considered
      personally useful by most respondents.

PMID- 21717840
TI  - An independent assessment of the Australian food industry's Daily Intake Guide
      'Energy Alone' label.
AB  - ISSUES ADDRESSED: A single thumbnail variant of the food industry's voluntary
      front-of-package Daily Intake Guide (DIG)--called the 'Energy Alone' thumbnail
      (DIG kJ)--has recently appeared on many energy-dense, nutrient-poor foods and
      beverages, especially soft drinks and confectionery. However, there is no
      published data to date that has assessed its merit. METHOD: A quota sample of 58
      Australian adults (50% female; 47% blue collar; mean age 35 years, range 18-59)
      was presented with photographs of three food packages alternatively labelled with
      DIG kJ, full DIG (five thumbnails) and Traffic Lights (TL) systems. Participants
      ranked each labelling system along seven-point scales for the following
      dimensions: 'interpretable, 'noticeable', 'useful' 'and' a deterrent to
      purchasing unhealthy snack foods: Participants were afterwards brought together
      in eight focus groups of 7-8 to discuss the merits of each system. RESULTS:
      Paired samples t-tests suggested the DIG kJ was rated significantly less
      "noticeable" ,'useful'or'a deterrent'than either the full DIG or TL systems. The
      TL system was also rated as significantly more'interpretable"and"a deterrent'than
      either variant of DIG. In the focus groups, participants described the DIG kJ as
      too small to be noticeable, too abstract to be meaningful, and of little
      practical use. Higher energy on food labels was also associated with positive
      health, rather than as a risk for overconsumption. CONCLUSION: The DIG kJ
      performed poorly against the TL and full DIG. Our results suggest it is an
      ineffective food labelling system, that is unlikely to affect consumer knowledge,
      awareness, attitudes, purchasing or consumption behaviours.

PMID- 21717841
TI  - Process evaluation of the advertising campaign for the NSW Get Healthy
      Information and Coaching Service.
AB  - ISSUE ADDRESSED: Introducing a new and free population-wide telephone service to
      assist adults to be more active, eat healthier and achieve a healthy weight
      requires large-scale marketing.The challenge is to understand the pattern of
      advertising that is effective at generating public awareness and interest in
      using the new service. METHODS: A mass media campaign, consisting mainly of
      television advertising, was launched in March 2009 to promote the NSW Get Healthy
      Information and Coaching Service (GHS).This included GHS-specific and re-badged
      National 'Measure Up' campaign television advertisements.The number of calls and
      website visits to the GHS were monitored during the first 10 months of the
      initiative. GHS participants were also asked where they heard about the service.
      RESULTS: Paid television advertising shows a dose-response relationship with
      contacts to the GHS.The 30-second GHS-specific advertising was significantly more
      effective at generating contacts compared to 'Measure Up' advertising, and
      compared to GHS advertising that involved the 15-second advertising. Participants
      were significantly more likely to report television advertising as their referral
      source during periods of GHS advertising when compared to 'Measure up'
      advertising. CONCLUSIONS: On-going marketing of state-wide prevention initiatives
      is necessary to achieve population-wide engagement. On the whole, specific GHS
      promoting messages were more effective in recruiting participants than the re
      badged national 'Measure Up' Campaign advertising.The relevance of the creative
      execution, the call to action and the length of time a viewer is exposed to the
      GHS details have an impact on the numbers of calls to the GHS.

PMID- 21717842
TI  - Role modelling unhealthy behaviours: food and drink sponsorship of peak sporting
      organisations.
AB  - ISSUE ADDRESSED: Organised sport provides an important setting for health
      promotion. Peak sporting organisations have a role in assisting and overseeing
      sports clubs, including providing funding opportunities. As such, sponsorship of
      these organisations may influence the funding of community sport. This study
      aimed to describe the nature and scope of peak sporting organisations'
      sponsorship, and particularly food and beverage company sponsors. METHODS: An
      analysis of national and state sporting organisations'websites for the nine most
      popular sports for children and from four Australian states and territories was
      conducted using a structured survey tool. Information collected included the
      number and type of sponsors and sponsorship policies.The nature of food and
      beverage sponsors was defined as more healthy or less healthy using criteria from
      a Delphi survey. RESULTS: 443 sponsors were identified across 55 websites.
      Overall, 9% of sponsors were food companies and 3% were alcohol manufacturers.
      The majority of food companies (63%) and alcohol manufacturers (100%) did not
      meet criteria as healthy sponsors. CONCLUSIONS: Sponsorship of peak sporting
      organisations is widespread and consists of a relatively high proportion of
      alcohol manufacturers and food companies, some of which produce products
      considered to be unhealthy.This sponsorship may influence community sport through
      sponsored sporting programs or by indicating sponsors' acceptability.

PMID- 21717843
TI  - Community perceptions of smoking bans in NSW licensed venues.

PMID- 21717844
TI  - The effectiveness of school travel access guides (TAGs).

PMID- 21717845
TI  - Serving multicultural elders: recommendations for helping professionals.
AB  - As demographic patterns shift in the United States, helping professionals are
      likely to see more clients of color, including those who are first-generation
      immigrants. Additionally, given the aging of the American population, helping
      professionals are likely to encounter more elderly clients and their families. It
      is crucial that helping professionals be prepared to respond to elders from
      various cultural populations in effective and respectful ways. This article gives
      an overview of how old age may interact with cultural identity. This information
      can be useful for professionals in many different settings working with elders
      from various cultural backgrounds.

PMID- 21717846
TI  - Innovative senior centers.

PMID- 21717847
TI  - Care management and the transition of older adults from a skilled nursing
      facility back into the community.
AB  - After hospitalization, many older adults require skilled nursing care. Although
      some patients receive services at home, others are admitted to a skilled nursing
      facility. In the current fragmented health care system, hospitals are financially
      incentivized to discharge frail older adults to a facility for postacute care as
      soon as possible. Similarly, many skilled nursing facilities are incentivized to
      extend the posthospitalization period of care and to transition the patient to
      custodial nursing home care. The resulting overuse of institution-based skilled
      nursing care may be associated with various adverse medical social and financial
      consequences. Care management interventions for more efficient and effective
      skilled nursing facility use must consider the determinants involved in the
      decisions to admit and maintain patients in skilled nursing facilities. As we
      await health care reform efforts that will address these barriers, opportunities
      already exist for care managers to improve the current postacute transition
      processes.

PMID- 21717848
TI  - Transnational caregiving: Part 1, caring for family relations across nations.
AB  - This article concerns how globalization and the aging of the world's population
      are affecting the already complex issue of intergenerational transnational
      caregiving. Globalization has caused an increase in workforce mobility with large
      numbers of individuals seeking employment overseas. This, coupled with increased
      longevity globally, has resulted in many workers leaving their elderly parents in
      need of care in their home countries. This has spawned caregiving across national
      borders, or caring for family relations across nations. Currently in the United
      States, not enough emphasis is given to family caregiving. Data compiled by AARP
      and the National Alliance for Caregiving estimate the economic value for this
      group of family caregivers in 2007 to be $375 billion, accounting for 34-52
      million family caregivers per given year. This does not include those families
      who are transnational caregivers. The seminal work in this emerging field has
      been done by social anthropologists Loretta Baldassar, Cora Velekoop Baldock, and
      Raelene Wilding, who have defined the components of transnational caregiving
      based on an ethnographic study using qualitative data to study nine immigrant
      communities in Western Australia. Although their research focused on caregiving
      from a distance, additional work has been added to the discussion by introducing
      the element of "care drain" and further cultural perspectives. Therefore, this
      research is an exploratory study on intergenerational transnational caregiving
      within the context of the changing world and its demographics. Within the context
      of globalization and global aging, the following questions are addressed: What is
      the significance of family caregiving? What is a transnational? How has
      technology changed "transnationalism" today? What are the elements that comprise
      transnational caregiving? How does culture play a role in transnational
      caregiving? What are some of the national initiatives undertaken by governments
      to aid in workforce issues and recognition of caregiving organizations? By
      exploring these questions, it is hoped that there will be a better understanding
      of transnational caregiving and its relevance in all societies.

PMID- 21717849
TI  - Local promise: maximizing enrollment into low-income Medicare programs through
      state-based consumer advocacy.

PMID- 21717850
TI  - Macrophytes in the Upper Parana River floodplain: checklist and comparison with
      other large South American wetlands.
AB  - Neotropical aquatic ecosystems have a rich aquatic flora. In this report, we have
      listed the aquatic flora of various habitats of the upper Parana River floodplain
      by compiling data from literature and records of our own continuous collections
      conducted during the period 2007-2009. Our main purposes were to assess the
      macrophyte richness in the Parana floodplain, to compare it with other South
      American wetlands and to assess whether the number of species recorded in South
      American inventories has already reached an asymptote. We recorded a total of 153
      species of macrophytes in the Upper Parana River floodplain, belonging to 100
      genera and 47 families. In our comparative analysis, a clear floristic split from
      other South American wetlands was shown, except for the Pantanal, which is the
      closest wetland to the Parana floodplain and, therefore, could be considered a
      floristic extension of the Pantanal. The species accumulation curve provides
      evidence that sampling efforts should be reinforced in order to compile a
      macrophyte flora census for South America. The high dissimilarity among South
      American wetlands, together with the lack of an asymptote in our species
      accumulation curve, indicates that the sampling effort needs to be increased to
      account for the actual species richness of macrophytes in this region.

PMID- 21717851
TI  - Phenotypic plasticity of Vaccinium meridionale (Ericaceae) in wild populations of
      mountain forests in Colombia.
AB  - Vaccinium meridionale is a promising crop for the Andean region of South America
      and is currently available only in the wild. Spontaneous populations of this
      plant are found across the Colombian mountains, but very few published records on
      this plant morphology are available. A zonification study of V. meridionale was
      conducted in four principal areas of a low mountain forest of Colombia (Provinces
      of Boyaca, Cundinamarca, Santander and Narino) in 2007. A total of 20 populations
      and 100 plants of V. meridionale were individually characterized and surveyed,
      using a list of 26 characters of morphological variables (9 quantitative and 17
      qualitative characters). Our results indicated that natural populations of V.
      meridionale might be found in the tropical forest under a highly heterogeneous
      climate and microclimate conditions, at different mountain regions between 2 357
      and 3 168masl. The shrubs of V. meridionale exhibited a high level of intra
      population variation in several quantitative (plant height, stem diameter) and
      qualitative (growth habit, ramification density, presence of anthocyanins in
      stems) morphological characters, suggesting an environmentally induced phenotypic
      plasticity. Plant height, stem diameter and foliar density were the most variable
      morphological traits, with coefficients of variation higher than 50%. However,
      several quantitative characters of its reproductive potential, such as berry
      dimensions, rachis length and number of flowers per inflorescence, resulted with
      low plasticity with coefficients of variation lower than 30.2%, indicating that
      these characters were genetically determined. The highest correlation
      coefficients (p < 0.05) resulted to be between fruit length and fruit width
      (0.90), leaf length and leaf width (0.78), plant height and stem diameter (0.60),
      and inflorescence length and flowers number per inflorescence (0.57). The results
      suggest that an important genetic resource exists for this species in the wild.
      Low variation in fruit size, which constitutes a target trait for plant breeders,
      could be useful for selection of cultivars of V. meridionale. The results of this
      study could also be applied in conservation programs aimed to protect these
      diverse populations in the mountain forests of Colombia.

PMID- 21717852
TI  - Effect of sucrose and methyl jasmonate on biomass and anthocyanin production in
      cell suspension culture of Melastoma malabathricum (Melastomaceae).
AB  - Melastoma malabathricum, belongs to the Melastomaceae family, is an important
      medicinal plant widely distributed from Madagascar to Australia, that is used in
      traditional remedies for the treatment of various ailments. Besides its medicinal
      properties, it has been identified as a potential source of anthocyanin
      production. The present study was carried out to investigate the effect of
      sucrose and methyl jasmonate and feeding time on cell biomass yield and
      anthocyanin production in cell suspension culture of M. malabathricum. Addition
      of different concentrations of sucrose into the cell culture of M. malabathricum
      influenced cell biomass and pigment accumulation. The addition of methyl
      jasmonate was found to have no effect on cell biomass but the presence of higher
      amount (12.5-50 mg/L) had caused a reduction in anthocyanin production and
      accumulation. MS medium supplemented with 30 g/L sucrose and 3.5 mg/L of MeJA
      added on cero day and 3rd day produced high fresh cell mass at the end of nine
      days of culture but did not support the production of anthocyanins. However,
      cells cultured in the medium supplemented with 45 g/L sucrose without MeJA showed
      the highest pigment content (0.69 +/- 0.22 CV/g-FCM). The cells cultured in MS
      medium supplemented with 30 g/L sucrose with 3.5 mg/L MeJA added on the 3rd and
      6th day of culture, showed the lowest pigment content (0.37-0.40 CV/g-FCM). This
      study indicated that MeJA was not necessary but sucrose was needed for the
      enhancement of cell growth and anthocyanin production in M. malabathricum cell
      cultures.

PMID- 21717853
TI  - Genetic molecular analysis of Coffea arabica (Rubiaceae) hybrids using SRAP
      markers.
AB  - In Coffea arabica (arabica coffee), the phenotypic as well as genetic variability
      has been found low because of the narrow genetic basis and self fertile nature of
      the species. Because of high similarity in phenotypic appearance among the
      majority of arabica collections, selection of parental lines for inter-varietals
      hybridization and identification of resultant hybrids at an early stage of plant
      growth is difficult. DNA markers are known to be reliable in identifying closely
      related cultivars and hybrids. Sequence Related Amplified Polymorphism (SRAP) is
      a new molecular marker technology developed based on PCR. In this paper, sixty
      arabica-hybrid progenies belonging to six crosses were analyzed using 31 highly
      polymorphic SRAP markers. The analysis revealed seven types of SRAP marker
      profiles which are useful in discriminating the parents and hybrids. The number
      of bands amplified per primer pair ranges from 6.13 to 8.58 with average number
      of seven bands. Among six hybrid combinations, percentage of bands shared between
      hybrids and their parents ranged from 66.29% to 85.71% with polymorphic bands
      varied from 27.64% to 60.0%. Percentage of hybrid specific fragments obtained in
      various hybrid combinations ranged from 0.71% to 10.86% and ascribed to the
      consequence of meiotic recombination. Based on the similarity index calculation,
      it was observed that F1 hybrids share maximum number of bands with the female
      parent compared to male parent. The results obtained in the present study
      revealed the effectiveness of SRAP technique in cultivar identification and
      hybrid analysis in this coffee species.

PMID- 21717854
TI  - Reproductive biology of common snook Centropomus undecimalis (Perciformes:
      Centropomidae) in two tropical habitats.
AB  - In Southeastern Mexico, Centropomus undecimalis is an important fish species of
      sport and commercial fisheries for coastal and riverine communities. Fisheries
      along rivers and coasts depend on migratory habits of this species, and these
      movements are probably related to reproduction. In spite of its economic
      importance, few studies have been conducted focusing on its reproductive biology,
      and this research aims to analyze these habits. Samples (fork length, somatic and
      gonads weight, and macroscopic maturity stages) were obtained from organisms
      collected by fishermen from the largest fishing cooperatives along the coastal
      and riverine areas of Tabasco, from July 2006 to March 2008. Fish size ranged
      from 34 to 112 cm fork length, with an average age of 6.42 years for males and
      9.12 years for females. In riverine areas, fish sizes ranged from 30 to 85 cm and
      the average age was 5.5 years for males and 6.6 years for females. Significant
      differences were recorded between lengths of males and females from the two areas
      (Kruskal-Wallis, p < 0.05). The male:female ratio was 1:0.68 in the coast, and
      1:0.16 in riverine areas. The length-weight relationship did not vary between
      both sexes among areas (ANCOVA, p > 0.05). A curve for eviscerated weight was
      calculated for both sexes, for coastal fishes SW = 0.0059 (FL)3.07, and the
      riverine ones SW = 0.0086 (FL) 2.98, with an isometric growth (b = 3). The period
      of maximum reproduction was from July to August, with temperatures of 28 to 30
      degrees C. A significant correlation between the gonadosomatic index (GSI) and
      rainfall was recorded for samples of both males and females from coastal areas (r
      = 0.63, r = 0.70) whereas only one positive correlation was recorded for riverine
      females (r = 0.57). The size at first maturity (L50) was estimated at 60 cm and
      80 cm (FL), corresponding to 5.5 and 8.5 years of age, for males and females,
      respectively. An important proportion of mature females of eight years and older,
      suggests that these ages contribute significantly to the reproductive biomass.
      The results indicate that due to changes in the exploitation period, we recommend
      to protect populations of the common snook.

PMID- 21717855
TI  - Diet, reproduction and population structure of the introduced Amazonian fish
      Cichla piquiti (Perciformes: Cichlidae) in the Cachoeira Dourada reservoir
      (Paranaiba River, central Brazil).
AB  - The Blue Peacock Bass (Cichla piquiti), native to the Tocantins-Araguaia river
      basin of the Amazon system, was introduced into the basin of the Paranaiba River,
      Parana River system. Cachoeira Dourada reservoir is one of a series of dams on
      the Paranaiba River in central Brazil, where this fish has become established. A
      study of its feeding spectrum, combined with information about its reproductive
      characteristics and population structure, would enable the current state of this
      species in the reservoir to be assessed and might provide useful data for the
      management of other species native to this habitat. This study showed that the
      peacock bass has no predators or natural competitors in the reservoir and that
      reproduces continuously, with high reproductive rates, and has a smaller median
      length at first maturity (L50) than other species of Cichla. Its successful
      establishment in habitats strongly affected by human activity should cause
      changes in the whole structure of the local fish communities. Nonetheless, in
      this reservoir, there appears to be some sharing of the functions of this species
      with native carnivorous fish, a situation that may be sustained by the presence
      of a wide variety of foraging fish.

PMID- 21717856
TI  - Bacterial infection of mudfish Clarias gariepinus (Siluriformes: Clariidae)
      fingerlings in tropical nursery ponds.
AB  - Bacterial infection among the most common cultured mudfish Clarias gariepinus in
      Africa, has become a cause of concern, because it constitutes the largest
      economic loss in fish farms. In order to provide useful biological data of the
      pathogens for good management practices, samples were collected monthly between
      January 2008 and December 2009 in three monoculture nursery ponds, located in
      three different positions: upriver (A, grassland), mid-river (B, mixed forest and
      grassland) and downriver (C, rainforest) along 200 km length of Cross River
      floodplains, Nigeria. A total of 720 fingerlings between 15.1 and 20.7 g were
      analyzed to determine the degree of infection. The bacterial pathogens were taken
      from their external surfaces, and were isolated and identified by standard
      methods. The caudal fins of fingerlings from pond A had the highest bacterial
      load (5.8 x 10(3) cfu/g), while the least counts (1.2 x 103 cfu/g) were
      identified on the head of fish from pond C, with Flexibacter columnaris as the
      major etiological agent. Pseudomonas fluorescens, Aeromonas hydrophila,
      Escherichia coli, Staphylococcus aureus and Micrococcus luteus were identified as
      co-isolates with P. fluorescens as dominant (0.7 x 10(2) cfu/mL) co-isolates in
      pond water. Clinical signs of five white spots with red periphery appeared on the
      external surface of infected fish. All the fish sampled, died after 4 to 9 days.
      There was no significant difference in the bacterial counts between different
      ponds, but the difference between fish organs/parts examined was significant.
      Fish from these ponds are therefore potentially dangerous to consumers and highly
      devalued, with the economic impact to producers. Preventive methods to avoid
      these infections are recommended.

PMID- 21717857
TI  - Sex determination in Turdus amaurochalinus (Passeriformes: Muscicapidae):
      morphometrical analysis supported by CHD gene.
AB  - Sex determination is important for conservation and population studies,
      particularly for reproduction programs of threatened species and behavioural
      ecology. Turdus amaurochalinus, Creamy-bellied Thrush, only exhibits sexual
      dimorphism during the breeding season, when males are considered to show intense
      yellow bills, and females and immature males show dark brown bills. The
      objectives of this study were: 1) to determine the sex of individuals using
      genetic techniques, and 2) to test the hypothesis that sex dimorphism can be
      detected by morphometry. This study was carried out at Parque Nacional da
      Restinga de Jurubatiba, a preserved area located on the North coast of Rio de
      Janeiro State. The birds were captured using ornithological nets, singly marked
      with metal rings, weighed, measured and had blood samples collected before being
      released. The sex of 42 T. amaurochalinus individuals was determined using the
      CHD gene marker. A total of 20 males and 22 females were identified from June to
      August, with peak capture frequency in June. Turdus amaurochalinus females and
      males differed significantly in morphometrical measures. The most important
      traits to distinguish males from females were wing length (Student t-test = 4.34,
      df = 40, p = 0.0001) and weight (Student t-test = 2.08, d f = 40, p = 0.044):
      females were heavier and had significantly shorter wing length than males.
      Females and males were correctly classified in 86% and 75% of cases,
      respectively, using Discriminant Analysis. The molecular analysis was the most
      secure method for sex determination in the studied species.

PMID- 21717858
TI  - Population parameters of the Pacific flagfin mojarra Eucinostomus currani
      (Perciformes: Gerreidae) captured by shrimp trawling fishery in the Gulf of
      California.
AB  - Shrimp trawling fishery in the Gulf of California captures a wide variety of non
      target species of fish, crustaceans, and mollusks that are relatively unknown.
      The Pacific flagfin mojarra Eucinostomus currani is a frequently found species in
      these catches, nevertheless, nothing is currently known about its population
      dynamics. To contribute to the knowledge on this fish species, we studied the
      size structure, growth, mortality, and the recruitment pattern during the 2004
      2005 seasons. A total of 6,078 mojarra were captured from 350 samples, with
      minimum and maximum lengths of 4.5 cm and a maximum of 21.0 cm. The average total
      length of the four major cohorts was 11.4, 13.7, 15.6 and 18.0 cm, corresponding
      to ages 0.9, 1.2, 1.6 and 2.2 years, respectively, being the most abundant the
      1.2 year-old group. The instant growth coefficient indicated moderate growth
      rates (K(s) = 0.81/year, K(E) = 0.85/year), corresponding to individuals living
      between 3.5 to 3.7 years. The estimated asymptotic lengths was L (infinity) =
      21.8 cm. In general, the population could be considered healthy: natural
      mortality (M = 1.53/year); total mortality (Z = 2.73/year); condition factor (K =
      0.01072); fishery mortality (F = 1.2/year) and exploitation rate (E = 0.43/year).
      The maximum reproduction period almost coincided with the closed season for
      shrimp fishing (March to August), thus we concluded that survival of the species
      is ensured because reproduction is indirectly protected.

PMID- 21717859
TI  - Air pollution in a tropical city: the relationship between wind direction and
      lichen bio-indicators in San Jose, Costa Rica.
AB  - Lichens are good bio-indicators of air pollution, but in most tropical countries
      there are few studies on the subject; however, in the city of San Jose, Costa
      Rica, the relationship between air pollution and lichens has been studied for
      decades. In this article we evaluate the hypothesis that air pollution is lower
      where the wind enters the urban area (Northeast) and higher where it exits San
      Jose (Southwest). We identified the urban parks with a minimum area of
      approximately 5,000 m2 and randomly selected a sample of 40 parks located along
      the passage of wind through the city. To measure lichen coverage, we applied a
      previously validated 10 x 20 cm template with 50 random points to five trees per
      park (1.5m above ground, to the side with most lichens). Our results (years 2008
      and 2009) fully agree with the generally accepted view that lichens reflect air
      pollution carried by circulating air masses. The practical implication is that
      the air enters the city relatively clean by the semi-rural and economically
      middle class area of Coronado, and leaves through the developed neighborhoods of
      Escazu and Santa Ana with a significant amount of pollutants. In the dry season,
      the live lichen coverage of this tropical city was lower than in the May to
      December rainy season, a pattern that contrasts with temperate habitats; but
      regardless of the season, pollution follows the pattern of wind movement through
      the city.

PMID- 21717860
TI  - Phenology, seed dispersal and difficulties in natural recruitment of the canopy
      tree Pachira quinata (Malvaceae).
AB  - Life history and recruitment information of tropical trees in natural populations
      is scarce even for important commercial species. This study focused on a widely
      exploited Neotropical canopy species, Pachira quinata (Malvaceae), at the
      southernmost, wettest limit of its natural distribution, in the Colombian
      Amazonia. We studied phenological patterns, seed production and natural
      densities; assessed the importance of seed dispersal and density-dependent
      effects on recruitment, using field experiments. At this seasonal forest P.
      quinata was overrepresented by large adult trees and had very low recruitment
      caused by the combination of low fruit production, high seed predation and very
      high seedling mortality under continuous canopies mostly due to damping off
      pathogens. There was no evidence of negative distance or density effects on
      recruitment, but a clear requirement of canopy gaps for seedling survival and
      growth, where pathogen incidence was drastically reduced. In spite of the strong
      dependence on light for survival of seedlings, seeds germinated readily in the
      dark. At the study site, the population of P. quinata appeared to be declining,
      likely because recruitment depended on the rare combination of large gap
      formation with the presence of reproductive trees nearby. The recruitment biology
      of this species makes it very vulnerable to any type of logging in natural
      populations.

PMID- 21717861
TI  - Traffic noise affects forest bird species in a protected tropical forest.
AB  - The construction of roads near protected forest areas alters ecosystem function
      by creating habitat fragmentation and through several direct and indirect
      negative effects such as increased pollution, animal mortality through
      collisions, disturbance caused by excessive noise and wind turbulence. Noise in
      particular may have strong negative effects on animal groups such as frogs and
      birds, that rely on sound for communication as it can negatively interfere with
      vocalizations used for territorial defense or courtship. Thus, birds are expected
      to be less abundant close to the road where noise levels are high. In this study,
      we examined the effects of road traffic noise levels on forest bird species in a
      protected tropical forest in Costa Rica. Data collection was conducted in a
      forest segment of the Carara National Park adjacent to the Coastal Highway. We
      carried out 120 ten minute bird surveys and measured road noise levels 192 times
      from the 19th to the 23rd of April and from the 21st to the 28th of November,
      2008. To maximize bird detection for the species richness estimates we operated
      six 12 m standard mist nets simultaneously with the surveys. The overall mist
      netting effort was 240 net/h. In addition, we estimated traffic volumes by
      tallying the number of vehicles passing by the edge of the park using 24 one hour
      counts throughout the study. We found that the relative abundance of birds and
      bird species richness decreased significantly with the increasing traffic noise
      in the dry and wet season. Noise decreased significantly and in a logarithmic way
      with distance from the road in both seasons. However, noise levels at any given
      distance were significantly higher in the dry compared to the wet season. Our
      results suggest that noise might be an important factor influencing road bird
      avoidance as measured by species richness and relative abundance. Since the
      protected forest in question is located in a national park subjected to tourist
      visitation, these results have conservation as well as management implications. A
      decrease in bird species richness and bird abundance due to intrusive road noise
      could negatively affect the use of trails by visitors. Alternatives for noise
      attenuation in the affected forest area include the enforcement of speed limits
      and the planting of live barriers.

PMID- 21717862
TI  - Successful treatment of pediatric endocarditis and pericarditis due to MRSA with
      linezolid.
AB  - The linezolid treatment for methicillin-resistant Staphylococcus aureus (MRSA)
      infection was sporadically reported in children. Here we describe a case of a 6
      month-old patient underwent mediastinal drainage and artificial conduit
      removement caused by MRSA infection. After that, linezolid treatment was started
      and bacteremia was resolved after 14 days of treatment. At discharge, he was no
      febrile, his blood culture were sterile. We report a case of a patient with MRSA
      endocarditis treatment with linezolid.

PMID- 21717863
TI  - Soil nutrients and liming on dry weight yields and forage quality of Signal grass
      (Brachiaria decumbens Stapf.), grown on Korat soil series (oxic paleustults) in
      northeast Thailand.
AB  - This experiment was carried out at Khon Kaen University Experimental Farm, Khon
      Kaen University, Thailand during the 2004-2005 aiming to investigate effect of
      phosphorus (P) and dolomite levels on dry weight yields (DWYs) and forage quality
      of Signal grass. A 4x3 factorial arranged in a Randomized Complete Block Design
      (RCBD) was used. Four P levels were: 0, 100, 200 and 400 kg P2O5 ha-1 and three
      dolomite levels were: 0, 625 and 2,500 kg ha-1. The Signal grass plants were
      grown on Korat soil series, (Oxic Paleustults). A quadrat with a dimension of
      50x50 cm was used for grass yield harvests. Crude Protein (CP), Acid Detergent
      Fibre (ADF), Neutral Detergent Fibre (NDF) and Dry Matter Degradability (DMD)
      contents were determined. Tissues phosphorus and calcium contents were also
      analysed. The results showed that an increase in dolomite levels increased soil
      pH from 4.4 to 5.1 for levels 1 and 3, respectively. An increase in P levels
      increased available soil P from 4.56 to 28.38 ppm for levels 1 and 4,
      respectively. For the first year experiment, dolomite levels had no significant
      effect on DWYs, whilst P levels significantly increased but only up to level 2.
      The 2-year average DWYs reached 11,368 kg ha-1 for level 4 of P. With the first
      year rainy season harvests, P levels had its significant effect on ADF and DMD up
      to level 2 but not with CP and NDF. For the dry season harvests, P and dolomite
      levels had no significant effects on forage quality. Dolomite levels had no
      significant effect on P and Ca contents of the Signal grass tissues but an
      increase in P levels increased P contents. P and Ca contents, in most cases, were
      higher for the dry season than the rainy season.

PMID- 21717864
TI  - Serum level and antioxidant activity of ceruloplasmin in preeclampsia.
AB  - The antioxidants activities are decreased in the serum of women with
      preeclampsia. This study was aimed to determine the serum level and antioxidant
      activity of ceruloplasmin in preeclamptic women with gestational age over than 28
      weeks. In a cross-sectional and descriptive-analytic study performed on 60
      patients with preeclampsia (30 with mild and 30 with severe preeclampsia) and 30
      women with normal pregnancy (control) in Tabriz al-Zahra Hospital, serum level
      and antioxidant activity of ceruloplasmin was evaluated. The mean gestational age
      was 32.94+/-2.79 week in mild preeclampsia group, 32.17+/-3.00 week in severe
      preeclampsia group and 32.46+/-4.04 week in control group (p = 0.821). The mean
      serum level of ceruloplasmin was 0.62+/-0.16 g L-1 in mild preeclampsia group,
      0.61+/-0.23 g L-1 in severe preeclampsia group and 0.47+/-0.16 g L-1 in control
      group. The serum ceruloplasmin in control group was significantly lower (p =
      0.006). The mean antioxidant activity of ceruloplasmin was 562.54+/-139.79 in
      mild preeclampsia group, 556.21+/-190.94 in severe preeclampsia group and
      427.62+/-162.14 in control group. The antioxidant activity was measured as
      production of mg dL-1 of a colored product. The antioxidant activity of
      ceruloplasmin in control group patients was significantly lower (p = 0.002).
      Significant linear positive correlation was found between serum level of
      ceruloplasmin and antioxidant activity of ceruloplasmin (p<0.001 and r = 0.910).
      Serum level of ceruloplasmin is significantly lower in normal pregnancy than mild
      and severe preeclampsia. Antioxidant activity of ceruloplasmin is significantly
      lower in normal pregnancy than mild and severe preeclampsia.

PMID- 21717865
TI  - An estimating on of the economical value of Arsanjan Bonab Forest Park, Iran.
AB  - Using of amusement places always has been important for humankind. Therefore,
      assessment of value for this promenaded and usage of nature is necessary for
      future programming in management of natural resources. For this reason, this
      research will discuss an assessment of the promenaded value of Bonab Forest Park
      and determines a visitor's Willingness To Pay (WTP) for promenaded benefits
      obtained. In this study, two techniques are used for Contingent Valuation (CV) $
      Travel Cost (TC) method by Dichotomous Choice (DC). For determination of
      visitor's willingness to pay simple average method was employed. Results indicate
      that 94.3% of visitors are willing to pay for promenaded values at the Bonab
      Forest Park. The mean value for willingness to pay for the value of the park is
      0.38 $ for each person per month. Annual value for promenade in this park was
      calculated 3439.3 $ per hector. Other important results in this research show
      that forest park has promenaded value significantly and on the other hand, we can
      increase the usage, protection and numbers of tourists.

PMID- 21717866
TI  - Efficacy of intense pulsed light in hirsutism.
AB  - Unwanted hair growth presents a significant problem for many patients and
      considerable resources are spent to achieve a hair-free appearance. Our aim of
      this study was to further evaluate the efficacy of this method in hirsutism in
      our region. Sixty patients with idiopathic hirsutism presenting to Dermatology
      Clinics of Tabriz University of Medical Sciences from September 2007 to March
      2009 were classified in three groups regarding the site of hirsutism (chine,
      face, or mustache). All patients underwent IPL-therapy every month for six
      sessions. The changes in number and diameter of regional hairs were recorded at
      the end of each session. The patients had the mean age of 25.50+/-3.01 years (18
      33 year). The disease was in chin in 26 cases (43.3%), face in 18 patients (30%)
      and mustache in 16 (26.7%). The skin type was III in 49 (81.7%) or IV in 11
      (18.3%) patients. The positive therapeutic response after sixth session in total
      and in chin, face and mustache were 86.43, 88.66, 86.95 and 82.19%, respectively.
      The therapeutic response was not statistically significant in different body
      regions. The hair number in all treated regions was decrease significantly in
      each session in comparison with the first therapeutic session (p<0.05). Also, the
      hair diameter at the end of last session was decreased significantly in
      comparison with the first session in all treated regions (p<0.05). Regarding the
      high efficacy (86.42%) of IPL in treatment of facial hirsutism and absence of
      side effect, it is recommended as an effective treatment modality in hirsutism.

PMID- 21717867
TI  - Ecophysiological aspects of the interactions between Bromus kopetdaghensis and
      two nurse shrubs, Astragalus meschedensis and Acantholimon raddeanam in a
      semiarid rangeland.
AB  - Plant-plant interactions are known as the main biotic drivers of the vegetation
      dynamics. Therefore, understanding such processes is beneficial for the applied
      vegetation management. The aim of this research was to investigate the type and
      intensity of plant-plant interaction during the time course of a growth season.
      We studied ecophysiological aspects of facilitation and competition between two
      aridland shrubs, A. meschedensis Bunge and A. raddeanam Czernjak and one
      perennial grass, B. kopetdaghensis Krasch. Soil and plant sampling were carried
      out for shrubs and the grass that were either growing alone or the grass was
      growing under the canopy of shrubs. In Spring (May), soil humidity weight was
      higher under the shrubs+grass than the grass-only site. By the beginning of
      Summer (July) grass consumed the common soil water and rapidly terminated its
      yearly growth. Therefore, in August and September, soil humidity weight was lower
      under the shrubs+grass than shrub-only sites. Photosynthesis rate of B.
      kopetdaghensis was sharply reduced from the beginning towards the end of growth
      season, but was not varied between the different plant combinations. Leaf proline
      measurement in July indicated higher stress for B. kopetdaghensis that were
      growing under shrubs than those of open areas. In conclusion, we found
      facilitation effects of shrubs on the grass at the early times of growth season,
      but it shifted into the competition for water during summer times. The outcome of
      plant interaction was positive for the grass but negative for the shrubs,
      especially A. meschedensis.

PMID- 21717868
TI  - Dermatophytosis in Western Africa: a review.
AB  - Dermatophytic fungal infections are one of the most common infectious diseases in
      the world and are among the most commonly diagnosed skin diseases in Africa. They
      are caused by several dermatophyte species made up of three genera: Trichophyton,
      Microsporum and Epidermophyton. The pathogen spectrum and the clinical
      manifestations are totally different from those seen in other continents. The hot
      and humid environment in Africa is probably the major reason for their high
      prevalence. In this era of rapid movement from one continent to another and the
      increasing mobility of humans, agents of dermatophytic infections can no longer
      be said to be restricted within a given geographical area. This implies that an
      infection contracted in one part of the world may become manifest in another
      country where the etiological agent is not normally found. Therefore, updating
      our knowledge of the geographical distribution of the predominant causative
      agents of dermatophytosis will provide a better understanding of the risk factors
      and future epidemiologic trends. This review discusses the clinical signs and
      manifestations of dermatophytoses and attempts to summarize the current
      epidemiological trends on dermatomycosis of glabrous skin in Western Africa.

PMID- 21717869
TI  - Current research status, databases and application of single nucleotide
      polymorphism.
AB  - Single Nucleotide Polymorphisms (SNPs) are the most frequent form of DNA
      variation in the genome. SNPs are genetic markers which are bi-allelic in nature
      and grow at a very fast rate. Current genomic databases contain information on
      several million SNPs. More than 6 million SNPs have been identified and the
      information is publicly available through the efforts of the SNP Consortium and
      others data bases. The NCBI plays a major role in facillating the identification
      and cataloging of SNPs through creation and maintenance of the public SNP
      database (dbSNP) by the biomedical community worldwide and stimulate many areas
      of biological research including the identification of the genetic components of
      disease. In this review article, we are compiling the existing SNP databases,
      research status and their application.

PMID- 21717870
TI  - Prevalence and risk factors of diabetic nephropathy among Thai patients with type
      2 diabetes mellitus.
AB  - BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end stage renal
      disease. Clinically, DN is classified into 3 stages: microalbuminuria (MA),
      macroalbuminuria and ESRD. The prevalence and risk factors of DN among patients
      with type 2 diabetes mellitus (T2DM) in Thailand have not been well studied.
      OBJECTIVE: To assess the prevalence of DN in patients with T2DM and to determine
      their associated risk factors. MATERIAL AND METHOD: A cross-sectional study
      evaluating 877 T2DM patients from the out-patient department of seven public
      hospitals in Thailand was performed. Three random spot urine samples from all
      patients were collected during 3 consecutive months. Normoalbuminuria, MA and
      macroalbuminuria were defined as the presence of at least two out of three spot
      urine tests for urine albumin/creatinine ratio showing less than 30, 30-300 and
      more than 300 mg/gm respectively. RESULTS: Most patients were female, 60 years of
      age or older, with BMI above 25 kg/m2, a family history of DM, uncontrolled blood
      pressure, HbA1c above 7.0% and LDL above 100 mg/dl. The prevalence of
      normoalbuminuria, MA and macroalbuminuria was 62.8, 26.0 and 11.2% respectively.
      The prevalence of diabetic retinopathy in T2DM with normoalbuminuria, MA and
      microalbuminuria was 18.5, 35.5 and 48.0% respectively. Associated risk factors
      of DN were the duration of DM, HbA1c levels and uncontrolled hypertension.
      CONCLUSION: The prevalence of all DN was 37.2%. Associated risk factors of DN
      were the duration of DM, HbA1c levels and uncontrolled hypertension.

PMID- 21717871
TI  - Accuracy of urine dipstick test for microalbuminuria in type 2 diabetes mellitus
      patients.
AB  - BACKGROUND: Testing for microalbuminuria (MA) is an important tool for detection
      of the earliest clinical manifestation of diabetic nephropathy Dipstick test for
      MA is commonly used for screening MA but this dipstick test has not been
      validated in Thai patients with DM. OBJECTIVE: To evaluate the diagnostic
      accuracy of the dipstick test for MA in random spot urine samples of type 2
      diabetic mellitus patients, using urinary albumin to creatinine ratio (UACR) as
      the reference standard method. MATERIAL AND METHOD: Type 2 diabetic mellitus
      patients from the out-patient department of seven public hospitals were
      recruited. Random spot urine samples from all patients were screened for
      microalbuminuria by Combi-Screen dipstick test and UACR. RESULTS: A total of
      6,223 urine samples from 899 diabetic patients were screened for MA. From UACR
      criteria, these urine samples were classified as normoalbuminuria (4,016 samples,
      64.5%), MA (1,795 samples, 28.8%) and macroalbuminuria (412 samples, 6.6%). The
      dipstick test for MA had an overall sensitivity of 83.7%, specificity of 92.6%
      with a positive predictive value of 83.4% and a negative predictive value of
      92.7%. The area under the receiver operating characteristics curve of the
      dipstick test for MA is 0.9427. CONCLUSION: The dipstick test for MA may be a
      useful method to initially screen for MA in Thai patients with type 2 DM.

PMID- 21717872
TI  - Abnormal liver function test in Graves' disease: a prospective study of
      comparison between the hyperthyroid state and the euthyroid state.
AB  - BACKGROUND: Abnormal liver function test is sometimes seen in hyperthyroidism but
      no study had been carried out to compare liver function test in the hyperthyroid
      state and the euthyroid state. OBJECTIVE: This study aimed to find the prevalence
      of abnormal liver function test in Graves' disease and compare liver function
      test result in the hyperthyroid state with the euthyroid state. MATERIAL AND
      METHOD: This is a prospective study of 112 patients who had Graves' disease.
      These patients were new cases or recurrent cases of Graves' disease whose
      medication had been discontinue for more than 3 months. We followed-up 86
      patients received treatment with antithyroid drugs up to the euthyroid state and
      compared liver function test at diagnosis and in the euthyroid state. RESULTS: An
      abnormal level of serum globulin was the most abnormal liver function test
      results in Graves' disease at 30.4%, followed by an abnormal level of serum
      alkaline phosphatase of 25.0% and gamma-glutamyl transpeptidase (GGT) of 23.3%.
      The trend of GGT levels returned to normal but there was an increased in serum
      alkaline phosphatase after treatment until the euthyroid state in the follow-up
      group. CONCLUSION: Abnormal liver function tests in Graves' disease are common,
      after treatment until the euthyroid state, experienced an improvement in GGT
      level but also an increase in serum alkaline phosphatase level.

PMID- 21717873
TI  - Sensitivity of HRPT2 mutation screening to detect parathyroid carcinoma and
      atypical parathyroid adenoma of Thai patients.
AB  - OBJECTIVE: Detected HRPT2 mutation in parathyroid carcinoma or atypical
      parathyroid adenoma in sporadic hyperparathyroidism in Thai patients. MATERIAL
      AND METHOD: Samples of parathyroid carcinoma, typical (atypical) adenoma or
      hyperplasia were obtained for HRPT2 gene (17 exons) study since September 2001 to
      August 2010 both somatic and germline by SyBr Green PCR method. RESULTS:
      Parathyroid carcinomas and atypical parathyroid adenoma from 5 of 26 patients (10
      of 32 samples) were tested for HRPT2 mutations. Only somatic HRPT2 mutations were
      found in tumor from 2 patients but three patients found both somatic and germline
      HRPT2 mutations. Exon 15 of HRPT2 gene was the best sensitivity (sensitivity
      80.0%; p < 0.001, 95% CI 0.75-1.05) followed by exon 2 and exon 11 (sensitivity
      60.0%; p = 0.007, 95% CI 0.60-0.99) to detected parathyroid carcinoma or atypical
      parathyroid adenoma. CONCLUSION: HRPT2 mutations by SyBr Green PCR sensitive
      method to detected parathyroid carcinoma or atypical adenoma from benign
      parathyroid tissues. Exon 15 was the best sensitive to detected parathyroid
      carcinoma or atypical adenoma. Genotyping of such family members for germline
      mutation would focus implementation of clinical and biochemical monitoring of
      carriers of these mutations.

PMID- 21717874
TI  - Length of normal kidneys in Thai adults.
AB  - BACKGROUND: The length of kidney plays important role in diagnosing chronic
      kidney diseases. Kidney length can be measured by ultrasound, a cheap, convenient
      and noninvasive method. There is no report on the length of kidney in healthy
      Thai people. OBJECTIVE: To measure the length of normal kidneys in Thai adults
      volunteers by ultrasonography. MATERIAL AND METHOD: Healthy volunteers were
      recruited and the study was performed from April 2008 to June 2009. All
      volunteers were examined by the same standard ultrasound machine and the same
      radiologist throughout the study period. RESULTS: A total of 509 healthy
      volunteers were enrolled. The average lengths of left and right kidney were 10.24
      +/- 0.70 and 10.09 +/- 0.68 cm, respectively. Male kidney was bigger than the
      female kidney. Kidney length slightly increased until the age of 50 and become
      smaller at the age of 60 or more. Kidney length showed no correlation with age,
      body weight, body mass index and body surface area. CONCLUSION: The average
      lengths of left and right kidney were 10.24 +/- 0.70 and 10.09 +/- 0.68 cm,
      respectively. The length below 9.00 cm may indicate the state of kidney diseases.

PMID- 21717875
TI  - Laparoscopic radical prostatectomy technical aspects and experience with 100
      cases in Rajavithi Hospital.
AB  - OBJECTIVE: To determine technical aspects, preoperative data and perioperative
      outcomes in 100 cases of Laparoscopic Radical Prostatectomy (LRP) in Rajavithi
      Hospital. MATERIAL AND METHOD: Retrospective study from October 2005 to January
      2010, the first 100 consecutive patients who underwent LRP by the same surgeon
      were assessed in Rajavithi Hospital. Mean age, clinical stage, preoperative PSA
      level, Gleason score, operative time, estimated blood loss, perioperative
      complications, pathological stage and margin status were recorded and analyzed.
      Statistical analysis is shown in median (Q1-Q3), means +/- SD. RESULTS: The mean
      age was 67.9 +/- 6.5 years and preoperative PSA was 19.28 (0.39-105.10) ng/dl.
      The most clinical stage was T1c (64.8%), Median operation time was 425 (360-600)
      minutes and blood loss was 1,400 (800-2,475) ml. Laparoscopic bilateral pelvic
      lymph node dissection was 60 cases and pathologic positive lymph node was 8 cases
      (13%). The positive surgical margin rate was 21.6%. There were 28 post-operative
      complications: urine leakage more than 2 weeks (11 cases), rectal injury (10
      cases), hematoma (3 cases), lymphatic leakage more than 2 week (3 cases), DVT (1
      cases). Median catheter time was 7 (6-25) days. CONCLUSION: Laparoscopic radical
      prostatectomy is a feasible option for the surgical treatment of localized
      prostate cancer LRP can help improve vision and outcome of pelvic surgery which
      depends on clinical stage and learning curve.

PMID- 21717876
TI  - Comparison of efficacy and safety between foam sclerotherapy and conventional
      sclerotherapy: a controlled clinical trial.
AB  - BACKGROUND: Conventional sclerotherapy of varicose vein is performed by injection
      of a sclerosing substance into the vein. The modern use of foam in sclerotherapy
      in which sclerosants can be transformed into fine-bubbled foam by special
      techniques is developed. Many studies report about the better efficacy of foam
      therapy than conventional liquid therapy. OBJECTIVE: To assess the efficacy of
      sclerosant Polidocanol in foam form compared to liquid form and to determine
      safety profile by monitoring the complications (Pain, inflammation and
      pigmentation). MATERIAL AND METHOD: Randomized controlled trial study, fifty
      patients with symptomatic varicose veins underwent duplex ultrasonography for
      measurement of the diameter of the varices. All patients underwent one session of
      sclerotherapy with both sclerosants (foam and liquid Polidocanol). Efficacy was
      assessed at 15, 30 and 90 days after the sclerotherapy by duplex ultrasound and
      the safety was evaluated at 15, 30, 90 days. RESULTS: The efficacy of sclerosis
      was reported in total occlusion of 46 sites (92.0%) in foam therapy and of 38
      sites (76.0%) in Polidocanol liquid therapy after 90 days. The differences of
      occlusion for the two groups were statistically significant, foam therapy showed
      greater results than that of Polidocanol liquid therapy at 15 days, 30 days and
      90 days after therapy Pain and hyperpigmentation were significantly higher in
      foam group than that in liquid group at 15 days and 30 days. CONCLUSION: Foam
      sclerotherapy has greater efficacy for treating varicose veins comparing to
      conventional liquid sclerotherapy. However Pain, inflammation, and
      hyperpigmentation appeared more often with foam Polidocanol therapy.

PMID- 21717877
TI  - Clinicopathological characteristics of mucinous and non-mucinous adenocarcinoma
      in the colon and rectum in Rajavithi Hospital, Thailand.
AB  - BACKGROUND: The clinicopathological characteristics of colorectal mucinous
      adenocarcinoma (MA) are still controversial. Most of the reports suggested that
      MA were associated with worse clinicopathological behavior and poorer prognosis
      than non-mucinous adenocarcinoma (NMA) while the others showed no difference.
      OBJECTIVE: To compare clinicopathological characteristics and tumor recurrence of
      MA patients with those in NMA patients. MATERIAL AND METHOD: During the period of
      2000 to 2009 in Rajavithi Hospital, a total of 427 colorectal adenocarcinoma
      patient records consisting of 407 NMA and 20 MA were included in this study. Mean
      age, tumor location, TNM staging at diagnosis, T-stage, N-stage, preoperative CEA
      level and recurrent rate of MA patients were compared with those of NMA patients.
      RESULTS: The distribution of MA patients for gender, mean age, tumor location,
      TNM stage and preoperative CEA level were similar to those of NMA patients (all p
      > 0.05). Only the tumor recurrence in MA was significantly more common than that
      in NMA (p = 0.020, OR = 3.28 (1.14-9.43)), whereas the TNM stage was not
      significantly different from NMA (p = 0.530). The metastatic site and pattern of
      metastasis also showed no statistical significance (p = 0.125). CONCLUSION: The
      prognosis of MA is poorer than NMA. This may be associated with mucinous
      histological type itself.

PMID- 21717878
TI  - Serum AFP and AFP-L3 in clinically distinguished hepatocellular carcinoma from
      patients with liver masses.
AB  - OBJECTIVE: To determine the ability of alpha fetoprotein (AFP) and AFP-L3% serum
      level in discriminating hepatocellular carcinoma (HCC) from other types of liver
      mass. MATERIAL AND METHOD: This study was performed according to a prospective
      specimen-collection, retrospective-blinded-evaluation (PRoBE) design. A total of
      109 HCC patients and 51 patients with other types of liver mass were
      consecutively selected. The levels of AFP and AFP-L3% in their sera were
      measured. RESULTS: AFP levels in serum significantly elevated while AFP-L3%
      levels significantly decreased in HCC patients (AFP: p < 0.001, AFP-L3%: p <
      0.001). The area under the curve (AUC) of a receiver operating characteristic
      (ROC) curve analysis for the diagnosis of HCC of AFP and AFP-L3% was 0.71 and
      0.67, respectively. In addition, the serum level of AFP-L3% was significantly
      different between the small (mass occupying lesser than 50% of liver volume) and
      large (mass occupying more than 50% of liver volume) HCC (p = 0.040). CONCLUSION:
      The diagnostic accuracy of serum AFP and AFP-L3% could provide them as candidate
      biomarkers to discriminate patients with HCC from patients with other types of
      liver mass. Serum AFP-L3% as a prognostic factor for HCC should be further
      evaluated in more details.

PMID- 21717879
TI  - Correlation of BMI to pregnancy outcomes in Thai women delivered in Rajavithi
      Hospital.
AB  - OBJECTIVE: To establish the correlation between pre-pregnancy body mass index
      (BMI) and pregnancy outcomes in Thai women. Cultural modernization has changed
      lifestyle of Thai population including eating habits, leading to higher incidence
      of overweight in pregnant woman. This study aims to analyze the relationship
      between BMI of Thai women before pregnant and pregnancy outcomes. MATERIAL AND
      METHOD: The study population included 3,715 deliveries in Rajavithi Hospital,
      Bangkok, Thailand, between January 1, 2009 and December 31, 2009. The number of
      individuals in each adverse outcomes was compared with those in each BMI group.
      Odds ratios were calculated using normal BMI as reference. RESULTS: The
      overweight and obese BMIs resulted in significant risk of cesarean section, pre
      eclampsia and diabetes mellitus with [OR (95% CI)] 1.37 (1.13-1.68), 2.3 (1.4
      3.7), 4.02 (2.66-6.08) for overweight and 2.11 (1.53-2.90), 5.7 (3.3-9.8), 6.02
      (3.52-10.32) for obesity, respectively. The underweight BMI resulted in
      significant risk of preterm, very preterm, low birthweight (LBW) infant with [OR
      (95% CI)] 1.79 (1.48-2.16), 1.69 (1.15-2.47), 1.61 (1.27-2.03). Only obesity
      attributed to significant risk of macrosomia with [OR (95% CI)] 5.36 (2.73
      10.52). Both overweight and obesity led to significant risk of postpartum
      hemorrhage and severe postpartum hemorrhage with [OR (95% CI)] 1.71 (1.21-2.44),
      2.13 (1.08-4.22). No correlation was found between pre-pregnancy to stillbirth
      and congenital anomaly. CONCLUSION: Overweight and obesity could increase risk in
      cesarean section, pre-eclampsia, DM, PPH and severe PPH, but were protective
      factors of LBW. Only obesity played high risk of macrosomia. Underweight was a
      protective factor for cesarean section, pre-eclampsia, DM and PPH, but could
      cause risk in preterm, very preterm and LBW.

PMID- 21717880
TI  - Correlation between Reid's colposcopic index and histologic results from
      colposcopically directed biopsy in differentiating high-grade from low-grade
      squamous intraepithelial lesion at Rajavithi Hospital.
AB  - OBJECTIVE: To analyze the correlation and accuracy between Reid's colposcopic
      index (RCI) and histologic results from colposcopically directed biopsy (CDB) in
      differentiating high-grade squamous intraepithelial lesion (HSIL) from low-grade
      squamous intraepithelial lesion (LSIL). MATERIALS AND METHOD: A retrospective
      analysis of medical records of women who had abnormal Pap smear and underwent
      colposcopy, RCI scoring and CDB from January 1st, 2003 to December 31st, 2006 at
      Rajavithi Hospital was conducted. RESULTS: One hundred women were included in the
      present study. Compared with histological diagnosis from CDB, accuracy for four
      colposcopic criteria: margin pattern, color, vascular pattern and iodiness
      staining were 73.0%, 79.0%, 75.0% and 69.2%, respectively. Combining these
      variables into RCI showed 89.0% overall accuracy. Color and vascular pattern
      showed a good agreement with histologic results from CDB (Kendall's tau C = 0.68
      and 0.63; p < 0.05). Overall, RCI yielded a good agreement (Kendall's tau C =
      0.66; p < 0.05). CONCLUSION: RCI yields a good correlation with histology from
      CDB and it has high accuracy in differentiating HSIL from LSIL.

PMID- 21717881
TI  - Prevalence of low birthweight infants in HIV-infected women delivered in
      Rajavithi Hospital.
AB  - OBJECTIVE: To determine the prevalence of low birthweight infants in HIV-infected
      pregnant women delivered in Rajavithi Hospital and the relationship between
      antiretroviral drugs and low birthweight infants. MATERIAL AND METHOD: All
      numbers of low birthweight (LBW) infants and pregnant women with or without HIV
      infection delivered in Rajavithi Hospital during 2004-2008 from medical records
      were used. Two hundred HIV-infected pregnant women who delivered their infants at
      the same period were random for description and analysis. RESULTS: The prevalence
      of low birthweight infants delivered by HIV and non HIV-infected pregnant women
      were 12.6% (53/ 420) and 13.3% (4,249/31,975), respectively. There was no
      significant association between HIV infection and low birthweight (p = 0.688).
      Low birthweight infants delivered from HIV-infected pregnant women with and
      without antiretroviral therapy were 9.9% (7/41) and 13.6% (19/159), respectively.
      Various types of antiretroviral (ARV) drug including no ARV were significantly
      associated with LBW (p = 0.021). The one who received highly active
      antiretroviral therapy (HAART) had 2.27 times higher risk in having LBW.
      CONCLUSION: The prevalence of low birthweight infants among HIV-infected pregnant
      women was 12.6%. There was no association between HIV infection and LBW. HAART
      might be a risk of LBW.

PMID- 21717882
TI  - Wavefront and ocular spherical aberration after implantation of different types
      of aspheric intraocular lenses based on corneal spherical aberration.
AB  - BACKGROUND: To determine the ocular spherical aberration after using preoperative
      corneal spherical aberration guided aspheric IOL selection for cataract surgery.
      MATERIAL AND METHOD: Twenty-six eyes of cataract patients were scheduled for
      cataract surgery with aspheric IOL implantation based on preoperative corneal
      spherical aberration (SA) measured by Galilei corneal topography. The target
      postoperative total wavefront spherical aberration was zero. Three types of LOL
      were used in this study: TecnisZA9003 (Abbott Medical Optics Inc) with spherical
      aberration of -0.27 microm; Acrysof LQ SN60WF (Alcon Inc.) with spherical
      aberration of -0.20 microm and B&L Akreos with zero spherical aberration. Ocular
      spherical aberration was measured with a Wave Light machine 3 months
      postoperatively to demonstrate the total ocular spherical aberration. RESULTS:
      The preoperative mean corneal spherical aberration in the 3 groups was 0.351 +/-
      0.08, 0.181 +/- 0.04, and 0.056 +/- 0.03 microns respectively. All 26 eyes of 26
      patients completed the 3-month follow-up visit. Postoperative ocular spherical
      aberration of the 3 groups were: TecnisZA9003 (10 eyes) +0.023 +/- 0.011 microm;
      Acrysof IQ SN60WF (11 eyes) +0.045 +/- 0.018 microm; and B&L Akreos (5 eyes)
      +0.018 +/- 0.008 microm. These values were significantly lower than the predicted
      values in the Tecnis and Akreos groups and there was no correlation between the
      actual postoperative ocular spherical aberration and the predicted ocular
      spherical aberration in all groups. CONCLUSION: The implantation of an aspheric
      intraocular lens based on preoperative corneal spherical aberration is effective
      in reducing total ocular spherical aberration and improving visual function.

PMID- 21717883
TI  - Optic disc area and diameter of the central retinal vein occlusion fellow eyes,
      determined by optical coherence tomography.
AB  - OBJECTIVE: To investigate the diameters and disc area of central retinal vein
      occlusion fellow eyes (CRVO fellow eyes), whether there is any small diameter of
      the particular axis, which predisposing to central retinal vein occlusion (CRVO),
      or not. MATERIAL AND METHOD: A prospective analytic study between 78 CRVO fellow
      eye patients and 102 healthy control subjects was evaluated. Fast optic disc scan
      with Stratus OCT was obtained. RESULTS: Six axes of disc diameters, and disc area
      were not different between the groups. Analysis of the model excluding glaucoma
      within the study group (n = 59) revealed the similar outcome. CONCLUSION: Optic
      disc diameters and size in the CRVO fellow eyes were not different from normal
      subjects. Optic disc size appears not to be the pathogenesis of CRVO.

PMID- 21717884
TI  - 24-Hour intraocular pressure control between travoprost/timolol fixed
      combination, latanoprost/ timolol fixed combination and standard timolol in
      primary open angle glaucoma and ocular hypertension.
AB  - OBJECTIVES: To evaluate the efficacy between Travoprost 0.004%/Timolol 0.5% fixed
      combination, Latanoprost 0.005%/ Timolol 0.5% fixed combination once a day in the
      morning and Timolol 0.5% twice a day in a 24-hour intraocular pressure control
      (IOP). MATERIAL AND METHOD: The patients with primary open angle glaucoma and
      ocular hypertension was subjected. After 2-4 weeks of washout period, patients
      with daytime IOP > or = 21 mmHg and < 36 mmHg were admitted to the hospital for
      24-hour IOP monitoring every 3-hour interval starting from 9 am to 9 am the next
      day. The patients were randomly received Travoprost-Timolol fixed combination,
      Latanoprost-Timolol fixed combination once a day or Timolol twice a day in the
      studied eyes. Another 24-hour IOP monitoring was taken again 2 weeks later.
      RESULTS: 59 eyes from 32 patients were subjected. The mean initial IOP at 9 am
      was 21.6 mmHg. The mean reduction of IOP ranging from 1.6 to 7.3 mmHg for
      Travoprost-Timolol group, 1.5 to 8.2 mmHg for Latanoprost-Timolol group and 2.2
      to 5.6 mmHg for Timolol group. All three groups produced statistically
      significant reduction (p < 0.05) in mean IOP at all test times except; at 3 am
      for the Travoprost-Timolol group; at 3 am, 12 midnight-and 6 pm in the
      Latanoprost-Timolol group; and at 3 am and 9 pm in the Timolol group. The effects
      of IOP reduction of the combination drugs were greatest between 9 am and 3 pm
      with the morning dose of both combinations. There was no statistically
      significant difference in mean IOP reduction at any test time between the 2
      combination drug groups but they were both better than Timolol alone at 9 am and
      3 pm. CONCLUSION: A fixed combination of Travoprost 0.004% and Timolol 0.5% is as
      effective as a fixed combination of Latanoprost 0.005% and Timolol 0.5% and are
      better than Timolol 0.5% in 24-hour IOP control.

PMID- 21717885
TI  - Effect of radiation therapy to immunological and virological status in HIV/AIDS
      cancer patients, preliminary report.
AB  - OBJECTIVE: To describe effects of radiation therapy (RT) on immunological status
      (CD4 cell counts) and disease progression among HIV-positive cancer patients.
      MATERIAL AND METHOD: This prospective observational study was conducted among HIV
      positive cancer patients who received RT for curative intention of cancer in five
      selected hospitals in Thailand. All subjects received external beam radiation
      therapy, according to standard clinical practice guidelines of RT. Blood samples
      were taken 4 times for complete blood count, CD4 cell count and plasma HIV RNA
      viral load (HIV-VL) assays before and in the last week of RT, then three and six
      months after completion of RT. RESULTS: This preliminary study reported
      immunological status and HIV-VL before and the last week of RT, among 29 HIV
      positive female cancer patients enrolled from August 22, 2009 to June 30, 2010.
      The median age was 38 years (range 30-54). 27 patients (93 percent) had invasive
      cervical cancer. 26 patients (90 percent) were on antiretroviral treatment (ART).
      The mean baseline white blood cell (WBC) count, lymphocyte percentage were
      6,771.7 cells/microL and 31.7 percent respectively. The mean baseline CD4 cell
      count and CD4%, 387.8 cells/microL and 17.5 percent respectively. In the last
      week of RT, 25 subjects (86 percent) had CD4 count less than 200 cells/microL.
      The last week, mean WBC count, and mean lymphocyte percentage decreased to
      3,902.8 cells/microL and 17.5 percent respectively. Mean CD4 count number
      decreased to 157.7 cells/microL, but the mean CD4 % did not change. Four patients
      (14 percent) had increased HIV-VL after RT, of these two were not on ART and two
      were on ART for more than 1 year. CONCLUSION: The CD4 cell count was not a good
      surrogate for prediction of immunologic status of HIV-positive cancer patients
      during RT.

PMID- 21717886
TI  - A retrospective study comparing hypofractionated radiotherapy and conventional
      radiotherapy in postmastectomy breast cancer.
AB  - BACKGROUND: The conventional radiotherapy (CRT) in postmastectomy breast cancer
      is 1.8-2.0 Gy daily for 25 fractions, while hypofractionated radiotherapy (HFRT)
      delivered dose in fewer fractions with larger radiation intensity. The present
      study compares the efficacy of HFRT and CRT. MATERIAL AND METHOD: From 2004 to
      2006, 215 patients were retrospectively reviewed. Sixty seven patients received
      CRT and 148 patients received HFRT (2.65 Gy in 16-18 fractions). Five-year
      locoregional control (LRC), disease free survival (DFS), overall survival (OS)
      and toxicities were analyzed. RESULTS: Median follow-up was 39 months. Five-year
      LRC was 86.6% in CRT and 85.8% in HFRT (p = 0.852). Five-year DFS was 62.7% and
      69.6% (p = 0.136) in CRTand HFRT respectively. Patients who received HFRT had
      significant increase in 5-year OS (62.7% and 73.0% (p = 0.048). No difference of
      toxicities including changes in chest wall appearance, skin fibrosis, brachial
      plexopathy, arm edema, pulmonary fibrosis, rib fractures and cardiovascular
      events was found between two groups. CONCLUSION: HFRT is as effective as CRT in
      postmastectomy breast cancer.

PMID- 21717887
TI  - Effect of noise block using earplugs on propofol sedation requirement during
      extracorporeal shock wave lithotripsy.
AB  - OBJECTIVE: To determine effect of noise block using earplugs on reducing propofol
      infusion needed to maintain a constant bispectral index (BIS) values in patients
      undergoing extracorporeal shock wave lithotripsy (ESWL). MATERIAL AND METHOD:
      Fifty-eight patients (18-65 years) with nephrolithiasis undergoing ESWL, having
      ASA physical status I or II and have normal hearing function tested by audiometry
      were enrolled in this randomized, double-blind, controlled trial. Patients were
      randomized and allocated into two groups: noise blocked group (earplugs inserted
      into both ears) and control group (earplugs not inserted). Sedation by target
      controlled infusion was started with 1.2 mcg/mL of propofol and propofol target
      concentration was adjusted gradually by 0.2 mcg/ml every 5 minutes
      intraoperatively to achieve and maintain bispectral index (BIS) values within 75
      80% until the procedure finished. Total amount of propofol (mg), BIS values (%),
      ambient noise level (dB) and patient satisfaction (1-5) were measured. RESULTS:
      The amount of propofol infusion needed to maintain a constant BIS index value in
      patients undergoing ESWL in the noise blocked group was significantly lower than
      that in the control group (6.91 +/- 2.05 vs. 8.23 +/- 2.16 mg/kg/m2/hr, p =
      0.021). Patient satisfaction was similar in both groups (4 [1] vs. 4 [1], p =
      0.929). CONCLUSION: Noise diminution in ambient operating room can reduce the
      amount of propofol needed to maintain light sedation during ESWL.

PMID- 21717888
TI  - Newborn hearing screening at Rajavithi Hospital, Thailand: hearing loss in
      infants not admitting in intensive care unit.
AB  - BACKGROUND: Approximately one to two per 1000 newborns have hearing loss. Delay
      in detection of this disability leads to impaired development and may prevent the
      acquisition of speech. Early screening of hearing in newborns results in children
      receiving early language rehabilitation. OBJECTIVE: Determine the incidence of
      infants hearing loss in infants not requiring intensive care. MATERIAL AND
      METHOD: A prospective descriptive study in hearing loss in infants not requiring
      intensive care in Rajavithi Hospital between 17th January 2008 to 23rd December
      2009. Infants were screened with otoacoustic emissions (OAE), the results were
      divided into two groups, "pass" and "refer". The infants who failed the screening
      test were referred for further checks with second OAE and if they failed again,
      then the authors reassessed them with Auditory Steady State Response Test (ASSR).
      RESULTS: There were 508 newborns that needed intensive care out of 5,190 live
      births. 639 excluded because of unwilling to join the project. Therefore 4,043
      newborns were included in the study. There were 246 (6.1%) newborns who failed
      the first screening test but only 189 newborns were tested in second OAE because
      57 newborns were lost to follow-up. Twenty one newborns (11.1%) failed the second
      test. There were 15 newborn using ASSR for hearing threshold (6 newborns were
      lost to follow-up). There were 11 newborn was normal hearing, 2 newborn (rate
      49.5: 100,000) was mild hearing and moderate to severe hearing. CONCLUSION: The
      incidence of moderate to severe hearing loss in newborns who did not require
      intensive care was very low (rate 49.5: 100,000). However screening all newborns
      with OAE is still valuable because of severe impact to quality of life of late
      detection of hearing loss. Evaluation of hearing by ASSR was reliable.

PMID- 21717889
TI  - Comparison of academic achievement between medical students recruited by state's
      medical school entrance selection and by Rangsit University's own examination.
AB  - OBJECTIVE: College of Medicine, Rangsit University (RSU), is the only private
      medical school in Thailand. RSU College of Medicine recruiting method includes
      the examination together with state's medical schools and its own examination.
      The study aims to compare number of students in each group who passed, as
      required in the curriculum, pre-clinical subjects in 3 academic years, graduated
      Doctor of Medicine degree in 6 academic years, and finally passed the National
      Board examination for the Medical License following graduation. MATERIAL AND
      METHOD: All medical students enrolled in the College of Medicine from 2000 to
      2004 academic year were included in the study. The numbers of students from each
      group who passed pre-clinical level in 3 academic years, graduated in 6 academic
      years and finally passed the National Board examination for the Medical License
      following graduation were analyzed. RESULTS: During the year 2000 to 2004 College
      of Medicine recruited and enrolled 506 students, of these, 51 resigned. The
      number of students recruited by examination with other state's medical schools
      (first group) was 178 and by RSU examination (second group) was 277. Number of
      medical students who finished pre-clinical study and passed to clinical level in
      three years as required in the curriculum were 144 from 178 (80.9%) in the first
      group and 205 from 277 (74.0%) in the second group. Number of medical students
      who graduated in six years as required in the curriculum were 140 from 178
      (78.7%) in the first group and 202 from 277 (72.9%) in the second group. One
      hundred and thirteen from 178 students (63.5%) in the first group graduated
      within 6 years and passed the National Board Examination for Medical License
      following graduation. However, 149 from 277 students (53.8%) in the second group
      passed the same described process. CONCLUSION: Numbers of medical students
      admitted by examination together with other state's medical schools and
      examination by RSU itself are not significantly different in finishing pre
      clinical subjects in 3 years and graduated in 6 years. However, number of medical
      students recruited by examination with other state's medical schools passing the
      National Board Medical License examination at once following graduation in 6
      years is significantly more than those recruited by the RSU examination itself.

PMID- 21717890
TI  - Sweet's syndrome associated with Mycobacterium tuberculosis and cervical cancer:
      a case report.
AB  - A case of Sweet's syndrome associated with pulmonary tuberculosis and cervical
      cancer was reported. A 34-year-old Thai woman had pulmonary tuberculosis. After
      treatment with anti-tuberculosis for two months, she developed erythematous
      papules, plaque, pustule-like lesions at face and limbs, extremities, palms and
      soles spare truncal area. She also had high fever and muscle pain. Biochemical
      test at that time showed only leukocytosis and thrombocytosis, no correlation to
      any other infections, malignancy or connective tissue disease was found. We
      continued treating with anti-tuberculosis, simultaneously with systemic steroid
      and occasional colchicin for her cutaneous and hematologic conditions. The
      disease flared up for few episodes which could be controlled with systemic
      steroid before it subsided. However, she was diagnosed and treated for cervical
      carcinoma few years later. Eventhough is not very common, the chance of having
      tuberculosis and cervical cancer should be considered in patients presenting with
      Sweet's syndrome.

PMID- 21717891
TI  - Total laparoscopic right hepatectomy for large hepatocellular carcinoma: the
      first report in Thailand.
AB  - Limited cases of total laparoscopic right hepatectomy have been reported
      worldwide due to technically difficulty, especially in a large hepatocellular
      carcinoma (HCC). The objective of this article is to describe a simple technique
      for total laparoscopic right hepatectomy which was successfully performed in two
      patients with large HCC. Anterior approach technique combined with glissonian
      approach and principle of liver hanging maneuver were used. The detailed surgical
      technique was described. Total laparoscopic right hepatectomy for large HCC is
      feasible and safe.

PMID- 21717892
TI  - Endoscopic ultrasound-guided hepaticogastrostomy for hilar cholangiocarcinoma:
      the first trial in Thailand.
AB  - BACKGROUND: There are many palliative treatments for patients with unresectable
      malignant biliary obstruction, e.g. endoscopic retrograde
      cholangiopancreatography (ERCP) with stents, percutaneous transhepatic biliary
      drainage (PTBD) or surgery. We propose a new technique by using endoscopic
      ultrasound (EUS) with fluoroscopy to perform hepaticogastrostomy for palliative
      drainage far from the site of tumor to avoid tumor obstruction. MATERIAL AND
      METHOD: Between December 2005 and June 2006, two patients with severe jaundice by
      hilar cholangiocarcinoma were treated with this new procedure. The first case was
      a 44-year female post partial resection of tumor and Roux en Y
      hepaticojejunostomy and the second case was a 48-year male post ERCP and right
      hepatic stent. We used an electronic convex curved linear-array echo-endoscope
      with fluoroscope guided to drain left dilated intrahepatic duct to the stomach by
      inserting 8 Fr 60 mm metallic wallstent via lesser curvature. We performed under
      general anesthesia and followed-up every two weeks. RESULTS: There were former
      two patients failed to place the stents. Hepaticogastrotomy of both patients were
      our first successful trial but stent site of the first case was not good because
      the insertion was at esophagogastric junction. Total bilirubin of first and
      second case fell from 38.4 mg/dl to 27.3 mg/dl and 22.0 mg/dl to 3.4 mg/ dl in
      two weeks, respectively. No immediate complication was found and oral diet was
      well succeeded on the next day after procedure in both cases. The first case was
      dead after 32 days of operation from sepsis and hepatic failure. The second case
      was clinically much improved after 3 months and died from liver failure after 6
      months and 10 days. CONCLUSION: This new interventional EUS-guided
      hepaticogastrostomy is safe, feasible and may provide an alternative to surgery
      or PTBD or failed ERCP. It can improve the palliative treatment in hilar lesions
      because it's internal drainage and far from tumor site that promote fast
      recovery. However, long term study is still necessary to evaluate the results and
      cost-effectiveness of this technique.

PMID- 21717893
TI  - Langerhans' cell histiocytosis (LCH) in adolescence presented with central
      diabetes insipidus: a case report.
AB  - A 19-year-old Thai man presented with symptoms of central diabetes insipidus,
      exopthalmos and multiple ostolytic lesions of the cranial vault. Skin biopsy
      showed strongly positive CD 1a and S100. Electron microscopy showed rod shape and
      pentalaminar granules called "Birbeck" granules, a diagnosis compatible with
      Langerhans' cell histiocytosis (LCHs) or histiocytosis X. He was successfully
      treated with systemic chemotherapy.

PMID- 21717894
TI  - Organisation and management of public dentistry in Sweden. Past, present and
      future.
AB  - Professional organisations present challenges in management compared to producing
      companies, as control of the work lies within the professional groups themselves.
      Management in the Public Dental Health Service (PDHS) has an added difficulty in
      the two-tiered political governance in Swedish public dentistry. The aim of this
      thesis was to contribute to better understanding of the organisation and
      management of Human Service Organisations, especially the PDHS in Sweden, thereby
      contributing to long-term sustainability with due regard to the professionals.
      The aim was also to point to some future difficulties facing the PDHS and
      possible solutions to these. Four papers are included in the thesis. The first
      paper set out to define the professions in dentistry in Sweden from theories on
      professions. Dentists and, to a lesser degree; dental hygienists were the
      identified professional groups. The second paper scrutinised the external
      environment for dentistry in Sweden in the form of political decisions, i.e.,
      laws and regulations. The findings were that there can be a gap between the
      formal objectives and the factual behaviour from the political level, and that
      certain politically attractive ideas might reoccur at a later time despite good
      scientific arguments against them. Also indicated in this paper were ways to
      influence the political processes, by active participation in the early stages of
      decision-making The third paper dealt with the heads (CDOs) of the PDHS in the
      counties and is based on a questionnaire to them on management. It was found that
      ideas on management and organisation usually were embedded in the way the
      respective county council was organised. A strong belief in advantages of scale
      was noted, both for administration and also for dental care itself. The fourth
      paper compared overall job satisfaction among publicly employed dentists in
      Denmark and Sweden. A focus on size of clinic, on professional development and on
      influence at the work place was found to be important. The Danish dentists were
      generally more satisfied with their overall job situations than the Swedish ones.
      One explanation might be found in the environment for the respective service,
      with a much stronger element of competition in Sweden. Another aspect could be
      that the expectations of the Danish dentists might be more realistic when they
      entered the public service. In an appendix the history of the Swedish Public
      Dental Health Service is outlined. CONCLUSIONS: Dentists in Sweden are an
      established profession and dental hygienists are an emerging profession; they and
      society would benefit from a clearer delineation and definition of their unique
      competences. Political decision-making is not necessarily rational, and garbage
      can models or similar can give a better understanding of political processes.
      CDOs have a widespread belief in advantages of scale in administration as well as
      in care, which may pose future problems for the provision of dental care in
      sparsely populated areas. Overall job satisfaction, as part of Good Work, is
      founded in an atmosphere at the clinic that is focussed on professional values.
      It is noteworthy that PDHS dentists not born in Sweden had a lower job
      satisfaction than those born in Sweden. Perhaps a closer cooperation between the
      dental colleges and the PDHS might give the newly qualified dentists a more
      realistic view of the professional challenges in public dentistry, as well as
      giving the colleges access to the vast material on patients in the PDHS. The
      future division of tasks between the general dentists, dental hygienists and
      specialist care dentists has a great impact on the future need for personnel, and
      needs to be carefully analysed. The future diminishing numbers of dentists and
      the difficulty for the PDHS to retain dentists may be met by adapting the
      organisations to a much greater flexibility by allowing different teams to
      organise their own work. The possibilities to give the patients good service
      quality will depend on continued democratisation and less managerial control.
      Producer cooperatives, franchising, or similar, could be revisited and tried.
      However, such forms will require carefully designed contracts where the
      objectives and the outcomes are possible to define and to evaluate. The balance
      between good work for dentists, an efficient organisation and perceived good
      service to the public will be objects for further studies.

PMID- 21717895
TI  - Intra-oral soft tissue expansion and volume stability of onlay bone grafts.
AB  - Insufficient regeneration of missing bone and soft-tissue may present aesthetic
      or functional problems in patients indicated for dental implant surgery. Several
      techniques such as bone grafts, bone substitutes and guided tissue regeneration
      (GTR) have been described to rebuild a compromised alveolar ridge. Adequate soft
      tissue coverage of grafted bone and titanium-mesh is important to avoid exposure
      which may result in loss of the bone graft. The general aim of this thesis was to
      evaluate use of an osmotic tissue expander for expanding intra-oral soft tissue-
      creating a surplus of soft tissue-- in preparation for onlay bone grafting. An
      experimental rabbit model was used in studies (I), (II) and (III). In (I) an
      osmotic soft-tissue expander was placed bilaterally on the lateral wall of the
      mandible via an extra-oral approach. After two weeks of expansion the rabbits
      were killed and specimens were collected for histology. No inflammatory reaction
      and no resorbtion of the cortical bone occured. The periosteum was expanded and
      new bone formation was seen in the edges of the expander. In (II) and (III) the
      expander was placed under the periosteum in the same way as in (I): bilaterally
      in 13 rabbits in (II) and unilaterally in 11 rabbits in (III). After two weeks of
      expansion the expander was identified and removed. In (II) particulated bone was
      placed at the recipient site protected by a titanium mesh in one site and a bio
      resorbable mesh on the other site. In (III), DBBM particles and bone particles
      collected from the lateral border of the mandible separated by a collagen
      membrane was placed at the recipient site. The graft was protected by a pre-bent
      titanium mesh covered by a collagen membrane. After a healing period of 3 months
      specimens were collected for histological and SEM examination. New bone was
      growing in direct contact with the titanium mesh and bio resorbable mesh. The
      newly formed bone had the same calcium content as the mature bone in the base of
      the mandible. In the clinical study (IV) 20 patients were consecutively recruited
      and randomised into two groups. The experimental group (ten patients) had an
      osmotic soft tissue expander implanted. After two weeks of expansion the expander
      was removed and a particulated bone graft protected by a titanium mesh and a
      collagen membrane was fixed to the recipient site. Titanium implants were
      installed after a healing period of 6 months. The patients in the reference group
      had a bone block grafted from the anterior ramus fixated to the recipient site
      with one or two titanium mini screws. Implants were installed after a healing
      period of 6 months. A three dimensional optical measuring device was used to
      measure alterations in the soft tissue profile before each surgical procedure.
      The three-dimensional changes were then analysed on a PC. The results from the
      clinical study in patients confirmed the results from the experimental rabbit
      studies. The osmotic tissue expander expanded the soft tissue. Expander
      perforations of the soft tissue occurred in two patients. The optical
      measurements demonstrated a positive volume gain after soft tissue expansion and
      bone grafting. The expanded tissue could be used to cover a bone graft. There
      still was a risk of mesh exposure, even after soft tissue expansion, which
      occurred in two patients. In both groups, implants could be installed in the
      grafted bone in positions that would allow the crowns to fit aesthetically into
      the dental arch.

PMID- 21717896
TI  - Isoarnottinin 4'-glucoside, a glycosylated coumarin from Prangos uloptera, with
      biological activity.
AB  - Coumarins are a well-known group of natural products distributed in the plant
      kingdom especially in the family Apiaceae with various biological activities.
      Isoarnottinin 4'-glucoside is a simple glycosylated coumarin found previously in
      a few genera of Apiaceae, and its biological activities have not been previously
      described in details. In the present paper, the compound was isolated from
      Prangos uloptera (Apiaceae) leaves using HPLC techniques. Antimicrobial,
      phytotoxic and cytotoxic activities of the compound were evaluated by disk
      diffusion, lettuce assay and MTT method. Our results indicated that the compound
      has high antibacterial effect against Erwinia carotovora, a common plant pathogen
      with MIC value of 100 microg/mL. The compound also exhibited significant
      phytotoxic activity against lettuce and modest cytotoxic activity against HeLa
      cell line with IC50 of 0 .84 mg/mL. It could be concluded that isoamottinin 4'
      glucoside may play phytoalexin or allelopathic role for plant and may be a
      candidate for an antibacterial agent or a bioherbicide.

PMID- 21717897
TI  - Oncology Care in 2021: the FDA, Medicare, and healthcare reform.

PMID- 21717898
TI  - Screening for prostate cancer with PSA testing: current status and future
      directions.
AB  - The ultimate utility of the serum prostate specific antigen (PSA) assay as a
      screening test for reducing prostate cancer mortality has been an area of intense
      controversy since its introduction. PSA testing was not initially envisioned as a
      screening tool, but as a way to evaluate treatment responses in men with prostate
      cancer. Far in advance of evidence from randomized trials, the rapid and
      widespread uptake of PSA screening into US practice was initially driven by the
      intuitively logical assumption that the earlier one detects a malignancy, the
      more likely treatment is to be curative while minimizing associated harms.
      However, a growing body of observational evidence began to point to a substantial
      burden of associated overdiagnosis and overtreatment triggered by PSA testing.
      The interim results of several randomized clinical trials specifically designed
      to evaluate the impact of PSA testing on prostate cancer mortality have recently
      become available, but their incongruent results seem to have added fuel to the
      debate. This article presents a review of the literature on screening for
      prostate cancer with PSA testing; we include a detailed discussion of potential
      explanations for the contradictory results of the two largest randomized trials
      as well as reflections on the future of prostate cancer screening.

PMID- 21717899
TI  - Benefits and pitfalls of prostate cancer screening: "no proof of benefit" does
      not equal "proof of no benefit".

PMID- 21717900
TI  - Preventing prostate cancer overdiagnosis from becoming overtreatment.

PMID- 21717901
TI  - When to treat myelodysplastic syndromes.
AB  - The myelodysplastic syndromes represent a heterogeneous series of clonal
      hematologic neoplasms characterized by morphologic dysplasia, aberrant
      hematopoiesis and a variable risk of progression to acute myeloid leukemia. These
      syndromes have a complex pathobiology, and ineffective hematopoiesis is a well
      recognized feature of all of them. Normal blood cell maturation, differentiation,
      function, and survival are impaired, and these abnormalities contribute to the
      development of peripheral blood pancytopenia. The majority of patients succumb to
      complications of either bone marrow failure or leukemic progression. The fact
      that the majority of patients are elderly and have other comorbidities
      complicates therapeutic decision making and necessitates the development of
      individualized treatment strategies.

PMID- 21717902
TI  - Tricking or treating myelodysplastic syndromes.

PMID- 21717903
TI  - Myelodysplastic syndromes: where do we go from here?

PMID- 21717904
TI  - Evolving therapeutic paradigms for advanced prostate cancer.
AB  - Improving survival in metastatic castration-resistant prostate cancer (CRPC) is
      no longer an elusive goal. With the expansion of knowledge regarding the biology
      of the disease, we are witnessing a plethora of novel therapeutics that are
      undergoing testing in clinical trials. Since the approval of docetaxel for
      metastatic CRPC in 2004, three additional agents have demonstrated improvements
      in overall survival in randomized phase III trials: two agents (cabazitaxel and
      sipuleucel-T) were approved by the FDA in 2010, and a third (abiraterone) was
      approved in April of 2011. A threshold has clearly been crossed in the management
      of advanced prostate cancer; however, the impact on survival has been relatively
      modest, and efforts at personalized therapy have lagged behind those for other
      solid tumors. Further meaningful advances are needed, and the foundation for
      future clinical trials must be high-quality, high-impact translational science
      that focuses on disease biology, the defining of relevant pathways and validated
      predictive biomarkers, and adequate preclinical characterization of agents and
      combinations that will facilitate more personalized therapy.

PMID- 21717905
TI  - Advanced prostate cancer: new agents, new questions.

PMID- 21717906
TI  - Evolving therapeutic paradigms for advanced prostate cancer: what's needed to
      make optimal use of the new treatments.

PMID- 21717907
TI  - Targeting the insulin growth factor pathway in gastrointestinal cancers.
AB  - Insulin-like growth factor 1 (IGF-1)-directed therapy is currently at a
      crossroads. After decades of research, several agents targeting the IGF pathway
      are now in clinical trials. One recent phase III trial of the IGF-1R inhibitor
      figitumumab in patients with non-small-cell lung cancer was discontinued after an
      interim analysis showed no survival improvement. Clinical trials for patients
      with sarcoma have demonstrated impressive anti-tumor activity in cases where the
      IGF-1 pathway is activated, such as in Ewing sarcoma; however, acquired
      resistance has been common. Recently, randomized phase II trials combining IGF-1
      R with epidermal grown factor receptor (EGFR) inhibition in colorectal cancer
      have been completed. Preclinical studies have indicated that several biomarkers
      may have potential predictive value. Studies of IGF-1R inhibitors in
      gastrointestinal cancers are currently ongoing in pancreatic, gastroesophageal,
      hepatocellular, and colorectal cancers. A critical analysis of prior work in this
      field and a rational strategy for maximizing success on the basis of biomarker
      use are necessary.

PMID- 21717908
TI  - Targeting IGF-1R: at a crossroad.

PMID- 21717909
TI  - The IGF-1R pathway as a therapeutic target.

PMID- 21717910
TI  - Link found between inflammation and cancer.

PMID- 21717911
TI  - First-in-class antimitotic device approved for glioblastoma.

PMID- 21717912
TI  - Complementary therapies, herbs, and other OTC agents. Shiitake mushroom
      (Lentinula edodes).

PMID- 21717913
TI  - Econutrition and utilization of food-based approaches for nutritional health.
AB  - BACKGROUND: Macronutrient and micronutrient deficiencies continue to have a
      detrimental impact in lower-income countries, with significant costs in
      morbidity, mortality, and productivity. Food is the primary source of the
      nutrients needed to sustain life, and it is the essential component that links
      nutrition, agriculture, and ecology in the econutrition framework. OBJECTIVE: To
      present evidence and analysis of food-based approaches for improving nutritional
      and health outcomes in lower-income countries. METHODS: Review of existing
      literature. RESULTS AND CONCLUSIONS: The benefits of food-based approaches may
      include nutritional improvement, food security, cost-effectiveness,
      sustainability, and human productivity. Food-based approaches require additional
      inputs, including nutrition education, gender considerations, and agricultural
      planning. Although some forms of malnutrition can be addressed via supplements,
      food-based approaches are optimal to achieve sustainable solutions to multiple
      nutrient deficiencies.

PMID- 21717914
TI  - Food prices, household income, and resource allocation: socioeconomic
      perspectives on their effects on dietary quality and nutritional status.
AB  - BACKGROUND: The recent rise in agricultural commodity prices has been dramatic,
      and food prices are likely to follow an upward trend, at least in the medium
      term. Moreover, the recent financial crisis has also lowered incomes and
      increased food prices. Not only does this reduce dietary quality, but
      expenditures for health, sanitation, and education will decline, all of which
      will have a detrimental effect on health and nutrition outcomes. OBJECTIVE: To
      provide some perspectives on the role of major socioeconomic factors in driving
      health and nutrition outcomes. METHODS: We use demand elasticity parameters
      estimated from household-level survey data to simulate an increase in food
      prices, which is then mapped into energy and nutrient intakes. Furthermore, we
      also use household-level data to analyze the implications of unequal
      intrahousehold distribution of food for the nutritional status of adult women and
      female children. RESULTS: A 50% increase in food prices results in a decrease in
      energy intake of 5% to 15% and in a decrease in iron intake of 10% to 30%,
      depending on the strength of the induced income effect. In a country like the
      Philippines, this would be equivalent to an increase of 25 percentage points in
      the proportion of women not meeting their requirements for iron intake.
      CONCLUSIONS: Increasing food prices will make fighting micronutrient malnutrition
      in developing countries more difficult. In societies where preference is given to
      males in the intrahousehold distribution of nonstaple foods, this objective will
      be even more challenging.

PMID- 21717915
TI  - Bioavailability of micronutrients: stable isotope techniques to develop effective
      food-based strategies to combat micronutrient deficiencies.
AB  - BACKGROUND: The prevalence of micronutrient deficiencies, in particular those of
      iron, vitamin A, iodine, and zinc, is unacceptably high, especially among
      infants, children, and women of childbearing age in developing countries.
      Effective food-based strategies to combat these public health problems are
      therefore urgently needed. OBJECTIVE: As only a fraction of dietary iron, zinc,
      and provitamin A carotenoids is absorbed and utilized, i.e., bioavailable, access
      to information on micronutrient bioavailability is crucial in the development of
      food fortification strategies and interventions based on dietary diversification.
      METHODS: Review of literature. RESULTS AND CONCLUSIONS: This overview highlights
      the usefulness of stable isotope techniques to assess the bioavailability of
      nonheme iron and provitamin A carotenoids and the importance of generating data
      on micronutrient bioavailability to move the agenda forward.

PMID- 21717916
TI  - Biofortification: a new tool to reduce micronutrient malnutrition.
AB  - BACKGROUND: The density of minerals and vitamins in food staples eaten widely by
      the poor may be increased either through conventional plant breeding or through
      the use of transgenic techniques, a process known as biofortification. OBJECTIVE:
      HarvestPlus seeks to develop and distribute varieties of food staples (rice,
      wheat, maize, cassava, pearl millet, beans, and sweet potato) that are high in
      iron, zinc, and provitamin A through an interdisciplinary, global alliance of
      scientific institutions and implementing agencies in developing and developed
      countries. METHODS: In broad terms, three things must happen for biofortification
      to be successful. First, the breeding must be successful--high nutrient density
      must be combined with high yields and high profitability. Second, efficacy must
      be demonstrated--the micronutrient status of human subjects must be shown to
      improve when they are consuming the biofortified varieties as normally eaten.
      Thus, sufficient nutrients must be retained in processing and cooking and these
      nutrients must be sufficiently bioavailable. Third, the biofortified crops must
      be adopted by farmers and consumed by those suffering from micronutrient
      malnutrition in significant numbers. RESULTS: Biofortified crops offer a rural
      based intervention that, by design, initially reaches these more remote
      populations, which comprise a majority of the undernourished in many countries,
      and then penetrates to urban populations as production surpluses are marketed. In
      this way, biofortification complements fortification and supplementation
      programs, which work best in centralized urban areas and then reach into rural
      areas with good infrastructure. CONCLUSIONS: Initial investments in agricultural
      research at a central location can generate high recurrent benefits at low cost
      as adapted, biofortified varieties become available in country after country
      across time at low recurrent costs.

PMID- 21717917
TI  - Ecological approaches to human nutrition.
AB  - BACKGROUND: Malnutrition affects a large number of people throughout the
      developing world. Approaches to reducing malnutrition rarely focus on ecology and
      agriculture to simultaneously improve human nutrition and environmental
      sustainability. However, evidence suggests that interdisciplinary approaches that
      combine the knowledge bases of these disciplines can serve as a central strategy
      in alleviating hidden hunger for the world's poorest. OBJECTIVE: To describe the
      role that ecological knowledge plays in alleviating hidden hunger, considering
      human nutrition as an overlooked ecosystem service. METHODS: We review existing
      literature and propose a framework that expands on earlier work on econutrition.
      We provide novel evidence from case studies conducted by the authors in western
      Kenya and propose a framework for interdisciplinary collaboration to alleviate
      hidden hunger, increase agricultural productivity, and improve environmental
      sustainability. RESULTS: Our review supports the concept that an integrated
      approach will impact human nutrition. We provide evidence that increased
      functional agrobiodiversity can alleviate anemia, and interventions that
      contribute to environmental sustainability can have both direct and indirect
      effects on human health and nutritional well-being. CONCLUSIONS: Integrated and
      interdisciplinary approaches are critical to reaching development goals.
      Ecologists must begin to consider not only how their field can contribute to
      biodiversity conservation, but also, the relationship between biodiversity and
      provisioning of nontraditional ecosystem services such as human health. Likewise,
      nutritionists and agronomists must recognize that many of the solutions to
      increasing human wellbeing and health can best be achieved by focusing on a
      healthy environment and the conservation of ecosystem services.

PMID- 21717918
TI  - Reflections and projections...

PMID- 21717919
TI  - The effect of an exercise-based balance intervention on physical and cognitive
      performance for older adults: a pilot study.
AB  - BACKGROUND: Several exercise-based falls prevention interventions produced
      significant long-term reductions in fall rate, but few demonstrate long-term
      improvements in falls risk factors. A strong body of evidence supports a
      protective effect of aerobic or strength-training exercise on cognition.
      Individuals participating in an exercise-based balance improvement program may
      also experience this protective effect. This may contribute to the decreased rate
      of falls reported in the literature. PURPOSE: To determine if individuals
      participating in an evidence-based exercise program to reduce falls would
      demonstrate improvements in both physical and cognitive performance. METHODS: In
      this nonexperimental, pretest, posttest design study, 76 adults (65-93 years)
      participated in a scripted 12-week, 24 session exercise-based balance improvement
      program. Each 60 minute class incorporated balance, strength, endurance, and
      flexibility exercises. Participants completed baseline assessments of physical
      and cognitive performance measures 1 week prior and 1 week following the
      intervention. RESULTS: Fifty-two participants completed posttest measures. There
      were significant improvements in 3 physical performance measures (chair rise
      time, 360 degree turn, and 4 square step test). There also was similar
      improvement in the Symbol Digit Modality Test, a measure of processing speed and
      mental flexibility. When participants were dichotomized into 2 groups based on
      achieving/not achieving, a baseline walking speed of at least 1.0 meters/second,
      secondary analysis revealed greater improvements in cognitive performance
      measures of Trails A and Trails B tests by faster walkers compared to slower
      walkers. CONCLUSIONS: Participation in balance programs can have a positive
      impact on cognition and physical outcomes. This may provide insight about how
      exercise influences fall risk. Therapists can utilize this information clinically
      by educating patients about the potential positive effect of balance exercises on
      cognition.

PMID- 21717920
TI  - Application of a fall screening algorithm stratified fall risk but missed
      preventive opportunities in community-dwelling older adults: a prospective study.
AB  - OBJECTIVES: Evaluate the ability of the American and British Geriatrics Society
      fall prevention guideline's screening algorithm to identify and stratify future
      fall risk in community-dwelling older adults. METHODS: Prospective cohort of
      community-dwelling older adults (n = 117) aged 65 to 90 years. Fall history,
      balance, and gait measured during a comprehensive geriatric assessment at
      baseline. Falls data were collected monthly for 1 year. The outcomes of any fall
      and any injurious fall were evaluated. RESULTS: The algorithm stratified
      participants into 4 hierarchal risk categories. Fall risk was 33% and 68% for the
      "no intervention" and "comprehensive fall evaluation required" groups
      respectively. The relative risk estimate for falling comparing participants in
      the 2 intervention groups was 2.08 (95% CI 1.42-3.05) for any fall and 2.60 (95%
      Cl 1.53-4.42) for any injurious fall. Prognostic accuracy values were:
      sensitivity of 0.50 (95% Cl 0.36-0.64) and specificity of 0.82 (95% CI 0.70-0.90)
      for any fall; and sensitivity of 0.56 (95% CI 0.38-0.72) and specificity of 0.78
      (95% Cl 0.67-0.86) for any injurious fall. CONCLUSIONS: The algorithm was able to
      identify and stratify fall risk for each fall outcome, though the values of
      prognostic accuracy demonstrate moderate clinical utility. The recommendations of
      fall evaluation for individuals in the highest risk groups appear supported
      though the recommendation of no intervention in the lowest risk groups may not
      address their needs for fall prevention interventions. Further evaluation of the
      algorithm is recommended to refine the identification of fall risk in community
      dwelling older adults.

PMID- 21717921
TI  - Spatial and temporal parameters of self-selected and fast walking speeds in
      healthy community-living adults aged 72-98 years.
AB  - PURPOSE: There is limited data about typical performance for spatial and temporal
      measures of self-selected walking speed (SSWS) and fast walking speeds (FWS) for
      healthy adults older than 75 years. This study reports both velocity and spatial
      and temporal characteristics of walking by age group and gender for 118 community
      living adults between the ages of 72 and 98 years, mean age 84.8 (5.3) years,
      participating in a functional assessment clinic held at their continuing care
      retirement community. METHODS: Three trials of SSWS and 3 trials of FWS were
      captured using the GAITRite system (CIR Systems, Inc., Havertown, Pennsylvania).
      Velocity, normalized velocity, and other spatial and temporal parameters were
      calculated by GAITRite software. Independent ttests were used to evaluate
      differences by age and gender in demographic and anthropometric characteristics,
      and vital signs. Mean of 3 trials was used to develop performance values by age
      group and gender. Analysis of variance with appropriate post hoc testing was used
      to identify differences in gait characteristics by age and gender. RESULTS: There
      were no differences in anthropomorphic or vital signs by age group; men where
      taller and heavier as would be expected. There was a consistent age effect for
      both SSWS and FWS; gait velocity decreased as age increased, with significant
      differences between all decades of age. There was a significant gender effect,
      with men walking faster than women at SSWS and FWS. Even after normalizing SSWS
      and FWS to leg length, men walked faster than females. CONCLUSION: Data reported
      in this study of generally healthy older adults can be used by rehabilitation
      professionals to develop goals for functional walking speed and determine
      readiness for discharge for patients intending to return to community-living
      settings following their rehabilitation.

PMID- 21717922
TI  - Falls risk factors and a compendium of falls risk screening instruments.
AB  - CLINICAL PROBLEM: Falls are the leading cause of nonfatal injuries and injurious
      death among older adults; the aftermath of a fall stresses the health care system
      and places financial and psychological burdens on the patient and family. Because
      of this, fall prevention/risk reduction is a primary focus of numerous health
      care agendas. Over the last 2 decades, clinical research has provided clinicians
      with a variety of screening tools to quantify risk factors for falls. The
      majority of these measures focus on single domain intraindividual (eg, balance,
      strength, vision) or extraindividual (eg, home safety) falls risk factors. Some
      of these single domain instruments are easily introduced and administered by
      community lay leaders. When a more comprehensive assessment across multiple
      domains is required, the assessment cannot easily be administered by community
      program leaders. A physical therapist must determine which instrument, or
      combination of instruments, best targets risk of falling for a given older adult.
      PURPOSE: This integrative review of the literature will provide clinicians and
      researchers a concise examination of falls risks factors and a compendium of
      falls risk screening and assessment instruments. METHODS: Searchable databases,
      such as Medline and CINAHL were used to identify articles about strategies used
      for fall risk assessment. Information about measurement properties and
      characteristics were extracted and are presented in table format. CONCLUSION:
      Comparison of recently developed multidimensional and comprehensive screening
      algorithms for falls risk identification may aid in lowering the rates of false
      negatives associated with using very specific instruments that screen or assess
      in only 1 falls risk factor domain.

PMID- 21717923
TI  - Managing adverse challenges on the job.

PMID- 21717924
TI  - Don't be a Nellie: set your own work ethic high!

PMID- 21717925
TI  - Trichiasis: characteristics and management options.
AB  - Trichiasis is a common disorder in which eyelashes or cilia arising from their
      normal position are misdirected toward the ocular surface. This condition
      frequently causes ocular surface irritation and commonly results from eyelid
      inflammation and scarring which disrupts the direction of growth of cilia
      follicles. The knowledge of eyelid and cilia anatomy is important to the success
      of the treatment. Management options include epilation, electrolysis,
      radiofrequency ablation, laser photoablation, cryotherapy and surgical removal of
      the offending cilia. Treatment is made by the clinician based upon the number,
      distribution and severity of the trichiasis. Recognition and management of the
      underlying cause of the trichiasis should also be addressed. Nevertheless,
      recalcitrant or recurrent cilia are not unusual despite a systematic approach to
      this condition. This article will briefly discuss trichiasis and the relevant
      eyelid and cilia anatomy. Subsequently, the current treatment modalities for
      trichiasis and their complications will be described.

PMID- 21717926
TI  - Development of the Veterans Healthcare Administration (VHA) Ophthalmic Surgical
      Outcome Database (OSOD) project and the role of ophthalmic nurse reviewers.
AB  - Currently, ophthalmic surgical cases are not included in the Veterans
      Administration Surgical Quality Improvement Project data collection. Furthermore,
      there is no comprehensive protocol in the health system for prospectively
      measuring outcomes for eye surgery in terms of safety and quality. There are
      400,000 operative cases in the system per year. Of those, 48,000 (12%) are
      ophthalmic surgical cases, with 85% (41,000) of those being cataract cases. The
      Ophthalmic Surgical Outcome Database Pilot Project was developed to incorporate
      ophthalmology into VASQIP, thus evaluating risk factors and improving cataract
      surgical outcomes. Nurse reviewers facilitate the monitoring and measuring of
      these outcomes. Since its inception in 1778, the Veterans Administration (VA)
      Health System has provided comprehensive healthcare to millions of deserving
      veterans throughout the U.S. and its territories. Historically, the quality of
      healthcare provided by the VA has been the main focus of discussion because it
      did not meet a standard of care comparable to that of the private sector.
      Information regarding quality of healthcare services and outcomes data had been
      unavailable until 1986, when Congress mandated the VA to compare its surgical
      outcomes to those of the private sector (PL-99-166). 1 Risk adjustment of VA
      surgical outcomes began in 1987 with the Continuous Improvement in Cardiac
      Surgery Program (CICSP) in which cardiac surgical outcomes were reported and
      evaluated. 2 Between 1991 and 1993, the National VA Surgical Risk Study (NVASRS)
      initiated a validated risk-adjustment model for predicting surgical outcomes and
      comparative assessment of the quality of surgical care in 44 VA medical centers.
      3 The success of NVASRS encouraged the VA to establish an ongoing program for
      monitoring and improving the quality of surgical care, thus developing the
      National Surgical Quality Improvement Program (NSQIP) in 1994. 4 According to a
      prospective study conducted between 1991-1997 in 123 VA medical centers by Khuri
      et al., the 30-day mortality and morbidity rates for major surgeries had
      decreased by 9% and 30%, respectively. 5 Recently renamed the VA Surgical Quality
      Improvement Program (VASQIP) in 2010, the quality of surgical outcomes has
      continued to improve among all documented surgical specialties. Ophthalmic
      surgery is presumed to have a very low mortality rate and therefore has not been
      included in the VASQIP database.

PMID- 21717927
TI  - Branch retinal artery occlusion (BRAO).

PMID- 21717928
TI  - A new role in a busy practice.

PMID- 21717929
TI  - Faces of mercy.

PMID- 21717930
TI  - American Heart Association revises guidelines.

PMID- 21717932
TI  - The future of nursing: how will you transform nursing?

PMID- 21717931
TI  - Projecting your professional presence to the great beyond.

PMID- 21717933
TI  - Student nurses: the real frontline.

PMID- 21717934
TI  - Rising above disruptive behavior through professionalism.

PMID- 21717935
TI  - Up close: Caren Rose Cadiz Nituda.

PMID- 21717936
TI  - Learning from the little things.

PMID- 21717937
TI  - Breakthrough to nursing. Interview by Reneka Turner.

PMID- 21717938
TI  - Florence Nightingale (1810-1856): expanding societal limits.

PMID- 21717939
TI  - Professionalism in nursing: an old fashion ideal or new world mandate?

PMID- 21717940
TI  - From scrubs to stairs: the innovation of nursing excellence.

PMID- 21717941
TI  - Sharpening our professionalism through networking.

PMID- 21717942
TI  - National Student Nurses' Association, Inc. Code of Ethics: part II code of
      academic and clinical conduct and interpretive statements.

PMID- 21717943
TI  - Extraordinary work of the graduates of the (EXTRA).

PMID- 21717944
TI  - The importance of leadership for quality improvement.

PMID- 21717945
TI  - Evidence-informed decision making in a public health setting.
AB  - A process for systematically applying research to public health decisions was
      created for a large, public health organization in Canada. The 9-step process is
      supported by tools and training in accessing, appraising, and applying research.
      The process has been implemented throughout the organization using the change
      management theory developed by Kotter and Cohen.

PMID- 21717946
TI  - Building a culture of evidence-informed decision making in the community.
AB  - Growing fiscal pressures on health departments both provincially and locally
      necessitate tough decisions to be made. Although evidence-informed decision
      making may be commonly used for clinical decision making, the notion of evidence
      informed decision making for managing physician office practice processes,
      primary care, long-term care, or continuing care is limited. In healthcare, much
      data are collected, yet only a small percentage is actually used in meaningful
      ways. The Executive Training for Research Application (EXTRA) program strives to
      not only assist healthcare executives in acquiring necessary skills but also aims
      to lead cultural change in the Canadian healthcare system. This article describes
      three brief examples in which a vice president and director with EXTRA training
      have started to explore and use data to drive change in the community.

PMID- 21717947
TI  - A process improvement strategy for patient safety.
AB  - Most change processes fail. Success requires a systematic approach based on the
      best practices performed within a setting of significant commitment by the
      organization and its leaders and staff. The Institute for Healthcare Improvement
      (IHI) framework for improvement was used along with cascading organization-wide
      performance indicators with specific targets and the implementation of
      performance reporting. This approach successfully improved the two patient safety
      practices of acute myocardial infarction and medication reconciliation.

PMID- 21717948
TI  - Implementation of an integrated peri-operative quality management program at the
      Ottawa Hospital.
AB  - The 2004 Canadian Adverse Events Study estimated up to 23,750 potentially
      preventable in-hospital deaths occur annually; 51.4% of adverse events occurred
      with surgical care delivery. An integrated peri-operative quality management
      program has been implemented at The Ottawa Hospital using the American College of
      Surgeons National Surgical Quality Improvement Program (NSQIP). Using root cause
      analysis within a Plan-Do-Study-Act process improvement cycle, NSQIP will lead to
      improved peri-operative outcomes at the largest Canadian academic healthcare
      organization.

PMID- 21717949
TI  - Building physician capacity for transformational leadership.
AB  - Hospital physicians often have little formal preparation for leadership roles.
      The St. Joseph's Health Centre program for physician leaders includes a
      competency profile, personal development plans, self-directed reflective
      learning, and action learning groups to work on current challenges. The program,
      developed with the participation of physicians, is intended to promote a culture
      that recognizes and supports physicians' contribution to hospital leadership and
      in which medical staff and hospital administrators work collaboratively and share
      accountability.

PMID- 21717950
TI  - Physician, heal the system. Health care that is fairer and more rational is also
      more affordable.

PMID- 21717951
TI  - A quick fix to the food crisis. Curbing biofuels should halt price rises.

PMID- 21717952
TI  - Tortoises to the rescue. Rewilding islands and even continents could prove an
      effective method for reversing ecological catastrophe.

PMID- 21717953
TI  - Donor fatigue. The Red Cross has banned chronic fatigue syndrome sufferers from
      giving blood. But does a virus really cause the disease?

PMID- 21717954
TI  - Poor man's burden. Why are HIV rates so distressingly high in the southern U.S.?

PMID- 21717955
TI  - Why gadgets flop. A few lessons from the consumer electronics industry's most
      notorious failures.

PMID- 21717956
TI  - The limits of intelligence.

PMID- 21717957
TI  - The periodic table of the cosmos.

PMID- 21717958
TI  - The best medicine.

PMID- 21717960
TI  - Underground railroad. A peek inside New York City's subway line of the future.

PMID- 21717959
TI  - The last great global warming.

PMID- 21717961
TI  - Evolution of the eye. Scientists now have a clear vision of how our notoriously
      complex eye came to be.

PMID- 21717962
TI  - Hacking the lights out. Computer viruses have taken out hardened industrial
      control systems. The electrical power grid may be next.

PMID- 21717964
TI  - Bad boy of physics. Interview by Peter Byrne.

PMID- 21717963
TI  - Scent of a human. Decoding how a mosquito sniffs out human targets could lead to
      better traps and repellents that cut malaria's spread.

PMID- 21717965
TI  - The believing brain. Why science is the only way out of the trap of belief
      dependent realism.

PMID- 21717966
TI  - Baby's life, mother's schooling. Child mortality rates decline as women become
      better educated.

PMID- 21717969
TI  - Radiologic case study. Posterior Sternoclavicular Dislocation.

PMID- 21717970
TI  - Industry-driven Research: Have We Reached a Crisis Point?

PMID- 21717971
TI  - Arthroscopic medial retinacular imbrication for the treatment of recurrent
      patellar instability: a simple and all-inside technique.
AB  - Proximal soft tissue realignment is the main surgical intervention for recurrent
      patellar instability. In recent years, all-inside arthroscopic procedures or mini
      open surgeries have replaced traditional surgeries, which have more associated
      morbidity and poor cosmetic results. This article describes a simple and all
      inside arthroscopic technique for the operative treatment of recurrent patellar
      instability. Using 2 epidural needles in several steps and no accessory portals
      required, the medial patellar retinaculum is imbricated to the desired tension.
      The combination of lateral release and medial retinacular placation obviously
      improves the patellar tracking compared with preoperatively.

PMID- 21717972
TI  - Achilles tendon rupture and subsequent repair.

PMID- 21717973
TI  - Intramedullary nailing of proximal third tibial fractures: techniques to improve
      reduction.
AB  - Obtaining and maintaining an acceptable reduction of proximal third tibial
      fractures can be problematic. Deforming forces acting on the proximal fragment
      and the spaciousness of the intramedullary canal at this level contribute to this
      challenge during intramedullary nailing. Several surgical techniques have been
      developed to address this problem, including the use of a more lateral and
      proximal starting point, adjunctive plate fixation, blocking screws, semiextended
      nailing, and most recently the use of a retropatellar portal approach.
      Familiarity with these techniques is critical to achieve satisfactory results
      when nailing proximal third tibial fractures.

PMID- 21717975
TI  - Recurrent anterior shoulder instability associated with bony defects.
AB  - Mobility of the glenohumeral joint is facilitated through the complex interplay
      of soft tissue and osseous anatomy. Arthroscopic shoulder stabilization is
      commonly used in the surgical management of shoulder instability. However, the
      management of the unstable shoulder associated with bony defects (glenoid,
      humeral, or combined) can be challenging. Adequate recognition of bony defects is
      paramount to successful treatment and entails a careful history, clinical
      examination, and advanced radiographic imaging. Nonoperative methods of treatment
      are often insufficient for treating patients with large bony defects. Bony
      procedures, as opposed to soft procedures, may yield better outcomes in this
      patient population. However, respective surgical techniques used to address these
      defects are technically challenging with a significant learning curve and may
      lead to significant morbidity. This represents a paradigm shift in treatment and
      replaces the old paradigm of "open vs arthroscopic" instability surgery.

PMID- 21717977
TI  - Research is for everyone.

PMID- 21717979
TI  - Evidence-based practice guideline: wheelchair biking for the treatment of
      depression.
AB  - Depression is a problem that will continue to burden older adults and challenge
      health care providers. Failing to recognize and effectively treat depression in
      institutionalized older adults is sanctioning these members of society to live
      their final years in despair and emotional suffering. The wheelchair biking
      program described in this evidence-based practice guideline provides a
      refreshing, safe, innovative tool to address depression and improve quality of
      life in older adults.

PMID- 21717982
TI  - Metastases of the pelvis: does resection improve survival?
AB  - Limited data are available to compare the outcome of wide en bloc resection and
      curettage for pelvic metastases. Previous studies have reported that curettage is
      associated with high mortality and decreased survival compared to wide resection
      and have justified consideration of a radical surgical approach to achieve pain
      palliation and tumor control. In this study, we aimed to evaluate the role of
      curettage/marginal resection compared to wide en bloc resection for patients with
      pelvic metastases. The hypothesis was that wide resection does not improve
      survival even in patients with solitary pelvic metastases.Between 1985 and 2009,
      twenty-one patients with pelvic metastases were treated with wide resection (12
      patients) and curettage/marginal resection (9 patients) and adjuvants. Sixteen
      patients had solitary pelvic metastases. At a mean of 28 months (range, 2-152
      months), we found no difference in survival to death or local recurrence with
      wide en bloc resection compared to curettage or marginal resection, even in
      patients with solitary pelvic metastases. The overall survival to death and local
      recurrence was 30% and 47% at 60 months, respectively. Survival to death of
      patients treated with wide resection was 18% at 60 months compared to 62% at 60
      months of patients treated with curettage/marginal resection; no difference in
      survival to death between wide resection and curettage/marginal resection was
      observed even in patients with solitary pelvic metastases. Survival to local
      recurrence of patients treated with wide en bloc resection was 67% at 36 months
      compared to 26% at 36 months of patients treated with curettage/marginal
      resection; this was also not statistically significant. One patient treated with
      wide resection for a solitary pelvic metastasis had a postoperative complication.

PMID- 21717983
TI  - Research in THA and TKA from the United States has declined over the past decade
      relative to other countries.
AB  - Decreasing reimbursement, increasing surgical volumes, and prohibitive
      institutional review board polices potentially deter residents from entering the
      subspecialty of joint replacement, while also inhibiting research production by
      existing surgeons. Our hypothesis is that there has been a decline in total hip
      arthroplasty (THA) and total knee arthroplasty (TKA) research in the United
      States relative to other countries over the past decade.All original research
      involving THA and TKA published in The Journal of Bone and Joint Surgery,
      American Volume, Journal of Arthroplasty, and Clinical Orthopaedics and Related
      Research over the past decade was queried. Country of origin and level of
      evidence of each publication were documented. From January 1999 to December 2008,
      1724 original peer-reviewed research studies involving THA and TKA were
      identified. The percentage of publications from US institutions steadily declined
      from 65.8% in 1999 to 46.9% in 2008. The percentage of Level I and II studies
      from the United States increased from 9.7% in 1999 to 23.3% in 2008, which
      parallels the increase seen from all countries from 7.8% to 24.8% during the same
      decade.Despite the improving levels of evidence, the relative percentage of
      publications from the United States on THA and TKA has declined over the past 10
      years. In contrast to the relatively constant number from the United States,
      publications on THA and TKA from non-US institutions have increased over the past
      decade. These trends may have significant implications for future THA and TKA
      research in the United States.

PMID- 21717984
TI  - Do microfractures improve high tibial osteotomy outcome?
AB  - The aim of this study was to determine if microfractures improve the outcome of
      high tibial osteotomy in patients with medial compartmental osteoarthritis in
      genu varum. Forty patients presenting with Outerbridge grade III and IV
      chondropathies on the femoral and/or the tibial joint surface underwent high
      tibial osteotomy with Puddu plates (Arthrex, Inc, Naples, Florida) for primary
      medial compartment osteoarthritis in genu varum at our institution. Patients were
      randomly assigned to either the high tibial osteotomy plus microfractures group
      (A; n=20) or the high tibial osteotomy alone group (B; n=20). Final assessment
      was conducted 5 years postoperatively, including clinical response measured by
      the International Knee Documentation Committee (IKDC), Lysholm score, and patient
      satisfaction score. All patients were blinded to the treatment received and
      followed the same rehabilitation protocol. A statistically significant
      improvement between pre- and postoperative values was observed for Lysholm and
      IKDC scores in both groups, without any statistically significant difference
      between them. Regarding the satisfaction score, there were no differences between
      the 2 groups in terms of preoperative self-assessment (P>.05), whereas
      postoperative subjective satisfaction at 5-year follow-up was significantly
      higher in group A than in group B (P=.0036).Our study results provide further
      evidence that medial tibial osteotomy is an effective surgical option for
      treating a varus knee associated with medial degenerative arthritis in patients
      wishing to continue accustomed levels of physical activity. In particular,
      patient satisfaction was higher among those who underwent the combined treatment
      involving high tibial osteotomy to correct femorotibial angle and microfractures.

PMID- 21717985
TI  - Use of vacuum-assisted closure in pediatric open fractures with a focus on the
      rate of infection.
AB  - The use of the vacuum-assisted closure device (VAC; KCI, San Antonio, Texas) has
      given the orthopedist a new tool for the successful management of severe
      traumatic wounds and open fractures. While the VAC's role in the adult population
      is proving itself as an improved therapy compared to "traditional wound care,"
      it's role within pediatric orthopedics remains less well defined. Questions
      remain whether VAC therapy provides benefit regarding decreased infection rates
      as well as decreased need for extensive soft tissue coverage procedures. A review
      was therefore performed of a pediatric level I trauma center's experience using
      the VAC therapy for pediatric open fractures with a focus on the rate of
      superficial, deep, and chronic infection. A retrospective chart review spanning
      4.5 years of all pediatric patients younger than 18 years with an open fracture
      initially treated with VAC therapy was conducted at a level I pediatric trauma
      center. This yielded 28 patients with 37 open fractures aged 2 to 17 years who
      were initially treated with wound VAC therapy. Subsequent chart review of these
      patients was performed examining in-hospital records, operative notes, and
      clinical follow-up visits for documented cases of superficial, deep, or chronic
      infection. Of 37 open pediatric fractures treated with a wound VAC, there were no
      cases of superficial infection and 2 cases of deep infection for an overall
      infection rate of 5%. Both infections resolved with surgical intervention and
      antibiotics without chronic infection development. When compared with historical
      controls, the use of VAC therapy for pediatric open fractures appears to be an
      equally safe and effective modality to help reduce infection in pediatric open
      fractures and should be considered a valuable tool in treating these injuries.

PMID- 21717986
TI  - Analysis of the trauma section of the orthopaedic in-training examination.
AB  - The Orthopaedic In-Training Examination is a comprehensive test produced annually
      by the American Academy of Orthopaedic Surgeons, and was first administered in
      1963. At the time of the examination's conception, its objectives were to: (1)
      measure the knowledge of orthopedic residents and provide objective comparisons;
      (2) help determine acceptable minimal standards for trainees; and (3) help
      provide an objective assessment of orthopedic education. We retrospectively
      reviewed all Orthopaedic In-Training Examinations from 2004 to 2008, with
      particular focus on the questions listed in the musculoskeletal trauma domain on
      each year's program director report. The musculoskeletal trauma domain, including
      topics, recommended answers, and references, was reviewed to provide an
      educational resource for residents and residency programs when studying or
      designing educational curricula. The information in this analysis may help in
      development of a core musculoskeletal trauma knowledge base or facilitate
      determination of appropriate journal club and didactic lecture content.

PMID- 21717987
TI  - Surgical outcome following arthroscopic fixation of acromioclavicular joint
      disruption with the tightrope device.
AB  - The objective of this study was to evaluate the preliminary radiographic and
      clinical results of grade IV and V acromioclavicular joint disruption repair
      using the arthroscopic Arthrex acromioclavicular TightRope (Naples, Florida)
      fixation technique. Numerous procedures have been described for surgical
      management of acromioclavicular joint disruption. The TightRope device involves
      an arthroscopic technique that allows nonrigid anatomic fixation of the
      acromioclavicular joint. A cohort of 10 men and 2 women with a mean age of 43
      years (range, 25-61 years) underwent the acromioclavicular joint TightRope
      procedure between April 2007 and October 2009. Eleven patients had either
      Rockwood grade IV or V disruptions and 1 sustained a distal third clavicle
      fracture with acromioclavicular joint disruption. Data was collected from a chart
      review. Patients were evaluated clinically, radiographically, by the simple
      shoulder test, and by overall satisfaction. There were 2 failures of reduction
      and 1 loss of reduction at final radiographic follow-up. The rate of fixation
      failure was 16.6%. All patients had >110 degrees  of total elevation. The
      majority of patients obtained satisfactory functional results according to the
      Simple Shoulder Test averaging 11 of 12 questions answered positively (range, 7
      12; standard deviation, 1.50) and 11 of 12 patients were satisfied with the
      procedure. At final phone interview at approximately 2 years postoperatively, 6
      patients were lost to follow-up. The remaining patients were all satisfied with
      the procedure and no patients reported subjective loss of reduction or
      deterioration of function. Simple Shoulder Test average was maintained with 11 of
      12 positively answered questions (range, 7-12; standard deviation, 2.0) This case
      series revealed a high rate of fixation failure with the TightRope system. Still,
      most patients were satisfied with the procedure and achieved high functional
      shoulder results.

PMID- 21717988
TI  - Biomechanical evaluation of open suture anchor fixation versus interference screw
      for biceps tenodesis.
AB  - Biceps tenodesis provides reliable pain relief for patients with biceps tendon
      abnormality. Previous cadaver studies have shown that, for biceps tenodesis, an
      interference screw provides biomechanical strength to failure superior to that of
      suture anchors. This finding has led some providers to conclude that screw
      fixation for biceps tenodesis is superior to suture anchor fixation. The purpose
      of the current study was to test the hypothesis that the strength of a 2-suture
      anchor technique with closing of the transverse ligament is equal to that of
      interference screw fixation for biceps tenodesis.In 6 paired, fresh-frozen
      cadaveric shoulder specimens, we excised the soft tissue except for the biceps
      tendon and the transverse ligament. We used 2 different methods for biceps
      tenodesis: (1) suture anchor repair with closing of the transverse ligament over
      the repair, and (2) interference screw fixation of the biceps tendon in the
      bicipital groove. Each specimen was preloaded with 5 N and then stretched to
      failure at 5 mm/sec on a materials testing machine. The load-to-failure forces of
      each method of fixation were recorded and compared. Mean loads to failure for the
      suture anchor and interference screw repairs were 263.2 N (95% confidence
      interval [CI], 221.7-304.6) and 159.4 N (95% CI, 118.4-200.5), respectively.
      Biceps tenodesis using suture anchors and closure of the transverse ligament
      provided superior load to failure than did interference screw fixation. This
      study shows that mini-open techniques using 2 anchors is a biomechanically
      comparable method to interference fixation for biceps tendon tenodesis.

PMID- 21717989
TI  - Evaluation of knowledge of common hand surgery problems in internal medicine and
      emergency medicine residents.
AB  - Musculoskeletal disorders are the principal reason for primary care outpatient
      visits and make up 14% of visits to emergency departments, with the upper
      extremity as the most common site affected. However, formal musculoskeletal
      education is inconsistent in medical school and primary care residencies, with
      many first-year residents reporting a lack of confidence in examination and
      diagnosis of musculoskeletal conditions. The authors evaluated the level of
      knowledge of common upper-extremity conditions with a validated examination taken
      by internal medicine and emergency medicine residents. A 38-question upper
      extremity examination was created by a group of hand and upper-extremity surgeons
      from the Resident Education Committee of the American Society for Surgery of the
      Hand. The examination was reviewed by 30 hand fellowship directors, who rated
      each question on a Likert scale and determined a recommended passing percentage.
      The Web-based examination was taken by emergency and internal medicine residents
      from multiple institutions. The fellowship directors' recommended passing grade
      averaged 73%. The majority of respondents were in their first (33%) or second
      (33%) year of training. The average scores were 56% and 46% for the internal and
      emergency medicine residents, respectively. This evaluation of a cross-section of
      internal and emergency residents indicates a deficiency in knowledge of common
      upper-extremity conditions.

PMID- 21717990
TI  - Long-term results of dorsally displaced distal radius fractures treated with the
      pi-plate: is hardware removal necessary?
AB  - The purpose of this study was to evaluate the outcome of patients treated with
      open reduction and internal fixation (ORIF) using dorsal plates and screws
      (AO/ASIF pi-plate) for dorsally displaced fractures of the distal radius.
      Although extensor tendon rupture is a recognized complication of all distal
      radial fractures, there appears to be an increased risk of this using dorsal
      plating. In addition, there is the added complication of extensor tendon
      irritation and dorsal wrist pain, which may necessitate plate removal. The low
      profile pi-plates intended to overcome this problem have not done so, with quoted
      rates ranged from 19% to 55%.We treated 32 completely evaluated patients (13 men
      and 19 women) in our department between 2000 and 2004, with an average age of 46
      years. They underwent ORIF of dorsally displaced fractures of the distal radius
      using the specially designed pi-plate. Bone graft was used in 18 patients who had
      significant metaphyseal defect. Clinical examination, plain radiographs, and
      functional assessments using the modified Mayo Wrist Score were performed at an
      average follow-up of 86 months (range, 56-115 months). Satisfactory reduction was
      achieved in all 32 fractures at the time of operative fixation with no instances
      of loss of fracture reduction during the study period. According to the Mayo
      Wrist Score, 23 patients (72%) had excellent or very good results, 7 (22%) had
      fair results, and 2 (6%) had poor results. Two cases (6.25%) of extensor tendon
      rupture were noted during the first postoperative month, and 2 other patients
      showed progressive weakness of index finger extension 6 months postoperatively.
      The remaining 28 patients had no soft tissue problems.

PMID- 21717991
TI  - Assessing rotational deformity of the little finger.
AB  - Excessive scissoring or overlap of fingers can cause discomfort, weaken grip
      strength, and affect cosmesis. The treatment of little finger fractures is guided
      by the degree of scissoring or rotational deformity perceived in the digit. The
      purpose of this study is to assess the variation of little finger scissoring or
      overlap in the normal population using standard clinical examination. We
      evaluated 80 uninjured little fingers in 40 normal patients. The digital images
      of photographed hands, taken in both extension and flexion, were used to evaluate
      the overlap percentage of the adjacent fingernail as a proxy for rotation of the
      digits. Paired t tests were used for statistical analysis. The average fingernail
      overlap was 25% +/- 20%, ranging from 0% to 71%. The average overlap on the left
      hand was significantly less at 21% +/- 18% as compared to 30% +/- 21% on the
      right (P < .01). The average variation between hands in individuals was 16% +/-
      13%.This study confirms that overlap or scissoring of the little finger varies
      between the hands of a given individual. Our results question the usefulness of
      assessing rotational deformity of the little finger by checking for overlap and
      comparing with the contralateral side. This has implications not only in
      assessing patients for possible surgery, but also in planning and performing
      surgical reductions of acute fractures and for correction of malunions.

PMID- 21717992
TI  - Toxicity of polyhexanide and hydrogen peroxide on human chondrocytes in vitro.
AB  - The treatment of acute joint infections has an important impact on long-term
      outcome and remains an unsolved problem. The most frequent bacteria are
      staphylococci, streptococci, and gram-negative bacteria. In septic surgery,
      polyhexanide and hydrogen peroxide are the most frequently used local
      antiseptics. The aim of this study was to examine the hypothesis that antiseptics
      induce cell death of human chondrocytes after a short incubation time.Human
      chondrocytes were treated with different concentrations of polyhexanide and
      hydrogen peroxide. Toxicity analysis was determined by visualization of cell
      structure using light microscopy, lactate dehydrogenase release, and
      determination of living and total cell numbers after addition of polyhexanide and
      hydrogen peroxide. Light microscopic data revealed a defect cell structure after
      addition of both antiseptics. Lactate dehydrogenase activity showed a significant
      increase of enzyme expression after a short incubation with polyhexanide. The
      determination of vital chondrocytes showed a significant decrease of vital and
      total cell numbers after addition with polyhexanide and hydrogen peroxide.Both
      antiseptic solutions induce significant cell death of human chondrocytes after a
      short incubation time. Polyhexanide possibly has more toxic potential than
      hydrogen peroxide against human chondrocytes after an application >15 minutes.
      Therefore, both substances should only be applied for a short time (<15 minutes)
      and the joint irrigated to wash out the antiseptic substance prior to wound
      closure.

PMID- 21717993
TI  - Changes in blood pressure and related autonomic function during cervical traction
      in healthy women.
AB  - Cervical traction is a physical therapy procedure frequently used to treat
      cervical disk lesions, cervical spondylosis, and cervical facet joint lesions. We
      have observed rare cases of side effects in elderly patients, but not in women
      younger than 30 years.In this pilot study, 96 young women were randomly divided
      into 3 groups to study the effect of cervical traction with different traction
      weights on blood pressure, heart rate, heart rate variability, and correlated
      autonomic adjustment. Cervical traction weight used was 10% of the patient's body
      weight in group A (n=32), 20% in group B (n=32), and 30% in group C (n=32).
      Assessments of blood pressure, heart rate, heart rate variability, percentage of
      high- and low-frequency signals, and low-frequency/high-frequency ratio were
      performed before, during, and 20 minutes after traction. We found that systolic
      blood pressure, diastolic blood pressure, and heart rate variability elevated
      during cervical traction and returned nearly to original levels immediately after
      traction in group C, but not in groups A or B. There were no significant changes
      in heart rate, percentage of high- or low-frequency signals, and low
      frequency/high-frequency ratio in all 3 groups during or after cervical
      traction.Cervical traction with a traction weight approximately 10% to 20% of
      body weight can be safely provided without significant compromise of
      cardiovascular function. However, heavy traction weight (30% of body weight)
      should be avoided, especially for a patient with cardiovascular disease.

PMID- 21717994
TI  - The surgical treatment of Andersson lesions associated with ankylosing
      spondylitis.
AB  - Eight men with Andersson lesions associated with ankylosing spondylitis who
      underwent surgical treatment were reviewed for this study. Eight Andersson
      lesions were found in the 8 patients, and all presented as pseudoarthrosis.
      Including a patient with obvious vertebral body destruction, no obvious local
      kyphosis was observed. Spinal cord compression and neural deficit were observed
      in 1 patient. Without established instructions for the surgical treatment of
      Andersson lesions, we alternated the surgical technique for each patient.
      Therefore, 5 patients, including the patient with obvious anterior destruction
      requiring reconstruction, underwent surgical treatment with lesion curettage and
      anterior bone graft and fusion; 3 other patients underwent surgical treatment
      without lesion curettage and anterior bone graft. All surgeries were performed
      from a posterior approach. Posterolateral autograft was supplemented to posterior
      instrumentation with or without anterior bone graft.All 8 patients experienced
      pain relief immediately postoperatively. No evidence of non-union was observed on
      radiographs at the level of pseudoarthrosis at final follow-up, and no neural and
      infectious complications were observed. Based on these results, surgical
      treatment with only posterior instrumentation supplemented by posterolateral
      autograft was effective for patients with Andersson lesions without obvious
      vertebral body destruction requiring reconstruction. Anterior lesion curettage
      and bone graft were not necessary. Solid immobilization, achieved by posterior
      instrumentation, should be the focus of the treatment of Andersson lesions with
      ankylosing spondylitis.

PMID- 21717995
TI  - Treatment of focal osteochondral defects of the acetabulum with osteochondral
      allograft transplantation.
AB  - To our knowledge, treatment of focal osteochondral defects of the acetabulum with
      osteochondral allograft transplantation has not been described. As with
      osteochondral lesions of other weight-bearing surfaces, these defects may lead to
      disabling pain and early degenerative changes. In older patients who fail
      nonoperative treatment, hip arthroplasty is a reliable option to obtain pain
      relief and restore function. However, in young and active patients, it may be
      advantageous to restore joint congruity biologically. The clinical success of
      osteochondral allograft transplantation in the femoral condyles has been well
      documented, with over 25 years of experience. We propose similar treatment
      principles in the hip joint.This article presents the cases of a 24-year-old
      woman (patient 1) and a 32-year-old man (patient 2) with hip pain and dysfunction
      secondary to a focal osteochondral defect of the acetabulum. Both were treated
      with osteochondral allograft transplantation to the defect using a dowel
      technique. A magnetic resonance image at 18 months in both cases demonstrated
      incorporation of the allograft bone into the host acetabulum. At 24 months in
      patient 1 and 42 months in patient 2, radiographs showed no progressive
      osteoarthritis. Both patients' Hip Outcome Scores were 100 points
      each.Osteochondral allografts allow large areas to be resurfaced without donor
      site morbidity, and these grafts provide an immediate functional joint surface.
      Although it has not been proven in terms of long-term follow-up, we believe that
      osteochondral allograft transplantation for focal osteochondral defects of the
      acetabulum in young, active patients is a feasible option to restore joint
      congruity.

PMID- 21717996
TI  - Locally administered zoledronic Acid therapy for giant cell tumor of bone.
AB  - Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal
      region of long bones. Because of its high recurrence rate, local adjuvant
      therapies such as phenol or liquid nitrogen have been recommended. In the present
      study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered
      locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man
      presented with pain and swelling in the right knee. Plain radiographs showed an
      osteolytic lesion of the right proximal tibia. An open biopsy was performed and
      the intraoperative pathologic diagnosis was giant cell tumor of bone. Following
      biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of
      zoledronic acid was locally administered into the tumor lesion. Two months after
      the biopsy, curettage and bone grafting were performed. Sections were obtained
      during the curettage for histology to evaluate the response to bisphosphonate
      treatment. Histologic examination revealed massive tumor cell death in the lesion
      in which both stromal cells and osteoclast-like giant cells were necrotic.
      Curettage was performed and the defect was filled with a commercial preshaped
      hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after
      curettage, the patient had regained full range of motion and good function of the
      knee, and radiographs at 18 months after curettage revealed no recurrence of
      giant cell tumor of bone.

PMID- 21717997
TI  - Bipolar clavicular dislocation.
AB  - Bipolar clavicular dislocation rarely occurs. Although referred to by several
      different names (panclavicular dislocation, bifocal clavicle dislocation,
      traumatic floating clavicle, and periarticular clavicle dislocation), knowledge
      regarding appropriate treatment of this condition is limited. Conservative
      therapy remains the gold standard in asymptomatic individuals. In younger
      individuals with higher functional demands, or individuals with persistent pain
      or instability, open reduction with internal fixation of the acromioclavicular
      joint has also proven successful. In situations with continued medial
      instability, internal fixation can be used at both the acromioclavicular joint
      and sternoclavicular joint.Chronic bipolar dislocation may require total
      claviculectomy, especially when chronic dislocation has led to nonviable
      acromioclavicular and sternoclavicular joint viability. This article presents a
      chronic case of bipolar dislocation treated by complete claviculectomy.

PMID- 21717998
TI  - Barefoot-simulating footwear associated with metatarsal stress injury in 2
      runners.
AB  - Stress-related changes and fractures in the foot are frequent in runners.
      However, the causative factors, including anatomic and kinematic variables, are
      not well defined. Footwear choice has also been implicated in contributing to
      injury patterns with changes in force transmission and gait analyses reported in
      the biomechanical literature. Despite the benefits of footwear, there has been
      increased interest among the running community in barefoot running with proposed
      benefits including a decreased rate of injury. We report 2 cases of metatarsal
      stress fracture in experienced runners whose only regimen change was the adoption
      of barefoot-simulating footwear. One was a 19-year-old runner who developed a
      second metatarsal stress reaction along the entire diaphysis. The second case was
      a 35-year-old ultra-marathon runner who developed a fracture in the second
      metatarsal diaphysis after 6 weeks of use of the same footwear. While both stress
      injuries healed without long-term effects, these injuries are alarming in that
      they occurred in experienced male runners without any other risk factors for
      stress injury to bone. The suspected cause for stress injury in these 2 patients
      is the change to barefoot-simulating footwear. Runners using these shoes should
      be cautioned on the potential need for gait alterations from a heel-strike to a
      midfoot-striking pattern, as well as cautioned on the symptoms of stress injury.

PMID- 21717999
TI  - Lumbar ligamentum flavum hematoma treated with endoscopy.
AB  - Hematoma of the ligamentum flavum is a rare cause of neural compression, for
      which treatment has consisted of excising the hematoma via open surgical
      approaches, including total laminectomy or bilateral partial laminectomy. This
      article presents the first report of a microscope-assisted endoscopic
      decompression to resect a hematoma of the ligamentum flavum.A 52-year-old man
      presented with back and leg pain, as well as difficulty initiating micturation.
      Magnetic resonance imaging demonstrated an epidural mass at L5/S1 that was
      continuous with the facet joint. Visualization was obtained via an endoscope, and
      a reddish tan-brown solid mass was found beneath the ligamentum flavum. Thorough
      decompression of the cauda equine and nerve roots was undertaken. The patient's
      radicular leg pain and bladder function improved soon after the decompression.
      Histological examination of the ligamentum flavum revealed a consolidated
      hematoma with granulomatous change.A review of the English literature revealed 29
      cases of hematoma in the lumbar ligamentum flavum. Surgical decompression in
      these patients was accomplished with a standard open approach through
      hemilaminectomy (n=11), total laminectomy (n=10), or laminectomy followed by
      posterior fixation (n=3). The literature review did not identify any case of
      hematoma of the lumbar ligamentum flavum that was treated endoscopically. We
      expect our case may expand the indications for the endoscope in spine surgery.

PMID- 21718000
TI  - Highly efficient separation of a solid mixture of naphthalene and anthracene by a
      reusable porous metal-organic framework through a single-crystal-to-single
      crystal transformation.
AB  - The three-dimensional crystalline porous metal-organic framework [Ni(2)(MU(2)
      OH(2))(1,3-BDC)(2)(tpcb)](n) (1) [1,3-H(2)BDC = 1,3-benzenedicarboxylic acid;
      tpcb = tetrakis(4-pyridyl)cyclobutane] was used to separate a solid mixture of
      naphthalene and anthracene at room temperature via selective adsorption of
      naphthalene. The process involved a single-crystal-to-single-crystal
      transformation. The guest naphthalene molecules could be exchanged with ethanol,
      and the host, 1, could be regenerated by removal of the guest ethanol molecules.

PMID- 21718001
TI  - Isolation of pure disubstituted E olefins through Mo-catalyzed Z-selective
      ethenolysis of stereoisomeric mixtures.
AB  - Monoaryloxide-pyrrolide (MAP) complexes of molybdenum were employed for the
      selective ethenolysis of 1,2-disubstituted Z olefins in the presence of the
      corresponding E olefins. Reactions were performed in the presence of 0.02-3.0 mol
      % catalyst at 22  degrees C under 20 atm ethylene. We have demonstrated that the
      Z isomer of an easily accessible E:Z mixture can be destroyed through ethenolysis
      and the E alkene thereby isolated readily in high yield and exceptional
      stereoisomeric purity.

PMID- 21718002
TI  - Luminol fluorescence quenching in biomimicking environments: sequestration of
      fluorophore in hydrophobic domain.
AB  - The photophysical behavior of luminol (LH(2)) was studied in a variety of
      biologically relevant systems ranging from surfactants, cyclodextrin, and
      proteins using steady-state and time-resolved fluorescence spectroscopy. It was
      shown that, out of two possible LH(2) conformers present in solution, the
      sequestration of relatively less polar structure into the hydrophobic domain of
      biological media is the primary reason for decrease in fluorescence intensity.
      The efficacy of LH(2) fluorescence quenching is substantially higher in micellar
      subdomain of cationic surfactant and depends on the nature of the headgroup. The
      thermodynamic parameters like enthalpy (DeltaH) and entropy (DeltaS) change,
      etc., corresponding to the binding of LH(2) in the model water-soluble protein,
      bovine serum albumin (BSA), were estimated by performing the fluorescence
      titration experiment at different temperatures. The involvement of subdomain IA
      and IIA of BSA in LH(2) binding was confirmed from the ligand replacement process
      with bilirubin (BIL). The difference in ligand binding with structurally
      homologous human serum albumin (HSA) is discussed in terms of positive
      cooperativity among these two binding domains of BSA with a Hill coefficient
      (n(H)) value of 2.26 +/- 0.18 and a half-maximal concentration (K(0.5)) of 5.74
      +/- 0.23 MUM at 298 K.

PMID- 21718003
TI  - Impact of nanoclay on isothermal cold crystallization kinetics and polymorphism
      of poly(L-lactic acid) nanocomposites.
AB  - Poly(L-lactic acid) (PLLA) intercalated nanocomposite films containing 1, 2, 5,
      and 10% organically modified montmorillonite (OMMT) have been synthesized by the
      solvent casting approach. The thermal characteristics, isothermal cold
      crystallization kinetics, and structural changes of neat PLLA and its
      nanocomposites during annealing were studied by using differential scanning
      calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. DSC
      observation showed that melting temperature and final crystallinity were not
      affected significantly with OMMT loading. PLLA films with increasing OMMT content
      exhibited higher crystallization rates than neat PLLA during annealing and
      suggested that the silicate platelets act as a nucleation agent during annealing.
      The effect of OMMT content on the isothermal crystallization kinetics of PLLA was
      analyzed using the Avrami equation. An Avrami constant of 1-2 was observed,
      suggesting that crystallization proceeds through one-dimensional growth with
      heterogeneous nucleation. FTIR investigation showed a band at 922 cm(-1) at all
      T(a), and no band at 908 cm(-1) suggested that all samples form alpha crystal
      regardless of OMMT content or T(a).

PMID- 21718004
TI  - Use of a corona discharge to selectively pattern a hydrophilic/hydrophobic
      interface for integrating segmented flow with microchip electrophoresis and
      electrochemical detection.
AB  - Segmented flow in microfluidic devices involves the use of droplets that are
      generated either on- or off-chip. When used with off-chip sampling methods,
      segmented flow has been shown to prevent analyte dispersion and improve temporal
      resolution by periodically surrounding an aqueous flow stream with an immiscible
      carrier phase as it is transferred to the microchip. To analyze the droplets by
      methods such as electrochemistry or electrophoresis, a method to "desegment" the
      flow into separate aqueous and immiscible carrier phase streams is needed. In
      this paper, a simple and straightforward approach for this desegmentation process
      was developed by first creating an air/water junction in natively hydrophobic and
      perpendicular PDMS channels. The air-filled channel was treated with a corona
      discharge electrode to create a hydrophilic/hydrophobic interface. When a
      segmented flow stream encounters this interface, only the aqueous sample phase
      enters the hydrophilic channel, where it can be subsequently analyzed by
      electrochemistry or microchip-based electrophoresis with electrochemical
      detection. It is shown that the desegmentation process does not significantly
      degrade the temporal resolution of the system, with rise times as low as 12 s
      reported after droplets are recombined into a continuous flow stream. This
      approach demonstrates significant advantages over previous studies in that the
      treatment process takes only a few minutes, fabrication is relatively simple, and
      reversible sealing of the microchip is possible. This work should enable future
      studies in which off-chip processes such as microdialysis can be integrated with
      segmented flow and electrochemical-based detection.

PMID- 21718006
TI  - A comparative study of neural and mesenchymal stem cell-based carriers for
      oncolytic adenovirus in a model of malignant glioma.
AB  - Glioblastoma multiforme is a primary malignancy of the central nervous system
      that is universally fatal due to its disseminated nature. Recent investigations
      have focused on the unique tumor-tropic properties of stem cells as a novel
      platform for targeted delivery of anticancer agents to the brain. Neural stem
      cells (NSCs) and mesenchymal stem cells (MSCs) both have the potential to
      function as cell carriers for targeted delivery of a glioma restricted oncolytic
      virus to disseminated tumor due to their reported tumor tropism. In this study,
      we evaluated NSCs and MSCs as cellular delivery vehicles for an oncolytic
      adenovirus in the context of human glioma. We report the first preclinical
      comparison of the two cell lines and show that, while both stem cell lines are
      able to support therapeutic adenoviral replication intracellularly, the amount of
      virus released from NSCs was a log higher than the MSC (p < 0.001). Moreover,
      only virus loaded NSCs that were administered intracranially in an orthotopic
      glioma model significantly prolonged the survival of tumor bearing animals
      (median survival for NSCs 68.5 days vs 44 days for MSCs, p < 0.002). Loading
      oncolytic adenovirus into NSCs and MSCs also led to expression of both pro- and
      anti-inflammatory genes and decreased vector-mediated neuroinflammation. Our
      results indicate that, despite possessing a comparable migratory capacity, NSCs
      display superior therapeutic efficacy in the context of intracranial tumors.
      Taken together, these findings argue in favor of NSCs as an effective cell
      carrier for antiglioma oncolytic virotherapy.

PMID- 21718007
TI  - Mutation in the flavin mononucleotide domain modulates magnetic circular
      dichroism spectra of the iNOS ferric cyano complex in a substrate-specific
      manner.
AB  - We have obtained low-temperature magnetic circular dichroism (MCD) spectra for
      ferric cyano complexes of the wild type and E546N mutant of a human inducible
      nitric oxide synthase (iNOS) oxygenase/flavin mononucleotide (oxyFMN) construct.
      The mutation at the FMN domain has previously been shown to modulate the MCD
      spectra of the l-arginine-bound ferric iNOS heme (Sempombe, J.; et al. J. Am.
      Chem. Soc. 2009, 131, 6940-6941). The addition of l-arginine to the wild-type
      protein causes notable changes in the CN(-)-adduct MCD spectrum, while the E546N
      mutant spectrum is not perturbed. Moreover, the MCD spectral perturbation
      observed with l-arginine is absent in the CN(-) complexes incubated with N
      hydroxy-L-arginine, which is the substrate for the second step of NOS catalysis.
      These results indicate that interdomain FMN-heme interactions exert a long-range
      effect on key heme axial ligand-substrate interactions that determine substrate
      oxidation pathways of NOS.

PMID- 21718008
TI  - Kinetics and dynamics of DNA hybridization.
AB  - DNA hybridization, wherein strands of DNA form duplex or larger hybrids through
      noncovalent, sequence-specific interactions, is one of the most fundamental
      processes in biology. Developing a better understanding of the kinetic and
      dynamic properties of DNA hybridization will thus help in the elucidation of
      molecular mechanisms involved in numerous biochemical processes. Moreover,
      because DNA hybridization has been widely adapted in biotechnology, its study is
      invaluable to the development of a range of commercially important processes. In
      this Account, we examine recent studies of the kinetics and dynamics of DNA
      hybridization, including (i) intramolecular collision of random coil, single
      stranded DNA (ssDNA), (ii) nucleic acid hairpin folding, and (iii) considerations
      of DNA hybridization from both a global view and a detailed base-by-base view. We
      also examine the spontaneous single-base-pair flipping in duplex DNA because of
      its importance to both DNA hybridization and repair.  Intramolecular collision of
      random coil ssDNA, with chemical relaxation times ranging from hundreds of
      nanoseconds to a few microseconds, is investigated both theoretically and
      experimentally. The first passage time theory of Szabo, Schulten, and Schulten,
      which determines the average reaction time of the intrachain collision, was
      tested. Although it was found to provide an acceptable approximation, a more
      sophisticated theoretical treatment is desirable.  Nucleic acid hairpin folding
      has been extensively investigated as an important model system of DNA
      hybridization. The relaxation time of hairpin folding and unfolding strongly
      depends on the stem length, and it may range from hundreds of microseconds to
      hundreds of milliseconds. The traditional two-state model has been revised to a
      multistate model as a result of new experimental observations and theoretical
      study, and partially folded intermediate states have been introduced to the
      folding energy landscape. On the other hand, new techniques are needed to provide
      more accurate and detailed information on the dynamics of DNA hairpin folding in
      the time domain of sub-milliseconds to tens of milliseconds.  From a global view,
      the hybridization of unstructured ssDNA goes through an entropy-controlled
      nucleation step, whereas the hybridization of ssDNA with a hairpin structure must
      overcome an extra, enthalpy-controlled energy barrier to eliminate the hairpin.
      From a detailed base-by-base view, however, there exist many intermediate states.
      The average single-base-pair hybridization and dehybridization rates in a duplex
      DNA formation have been determined to be on the order of a millisecond.
      Meanwhile, accurate information on the early stages of hybridization, such as the
      dynamics of nucleation, is still lacking.  The investigation of spontaneous
      flipping of a single base in a mismatched base pair in a duplex DNA, although
      very important, has only recently been initiated because of the earlier lack of
      suitable probing tools. In sum, the study of DNA hybridization offers a rich
      range of research opportunities; recent progress is highlighting areas that are
      ripe for more detailed investigation.

PMID- 21718009
TI  - Simultaneous application of the gradient theory and Monte Carlo molecular
      simulation for the investigation of methane/water interfacial properties.
AB  - This work is dedicated to the simultaneous application of the gradient theory of
      fluid interfaces and Monte Carlo molecular simulations for the description of the
      interfacial behavior of the methane/water mixture. Macroscopic (interfacial
      tension, adsorption) and microscopic (density profiles, interfacial thickness)
      properties are investigated. The gradient theory is coupled in this work with the
      SAFT-VR Mie equation of state. The results obtained are compared with Monte Carlo
      simulations, where the fluid interface is explicitly considered in biphasic
      simulation boxes at both constant pressure and volume (NPT and NVT ensembles),
      using reliable united atom molecular models. On one hand, both methods provide
      very good estimations of the interfacial tension of this mixture over a broad
      range of thermodynamic conditions. On the other hand, microscopic properties
      computed with both gradient theory and MC simulations are in very good agreement
      with each other, which confirms the consistency of both approaches. Interfacial
      tension minima at high pressure and prewetting transitions in the vicinity of
      saturation conditions are also investigated.

PMID- 21718010
TI  - Carbon nanotube electron ionization source for portable mass spectrometry.
AB  - Cold cathode carbon nanotubes (CNTs) are used in a low-voltage quadrupole ion
      trap mass spectrometer and shown to be a viable low-power alternative to filament
      sources for portable mass spectrometry instrumentation. No heating is necessary,
      and the power consumption depends only on the switching characteristics of the
      electronics. The CNT electron sources are mounted directly in the ring electrode,
      and their performance is compared directly with a filament source also mounted in
      the ring electron. Up to a 5 * 10(-4) Torr CO(2) environment, reflecting
      conditions expected during operation in a Mars atmosphere, the CNT emitters may
      provide up to 1 MUA of current over more than 200 h.

PMID- 21718011
TI  - Boron in drug discovery: carboranes as unique pharmacophores in biologically
      active compounds.

PMID- 21718012
TI  - tert-Butyl cation affinities of maingroup-element hydrides: effect of methyl
      substituents at the protophilic center.
AB  - We have conducted an extensive computational exploration of how the gas-phase
      tert-butyl cation affinities (t-BCA) of archetypal anionic and neutral bases
      across the periodic system are affected by stepwise replacement of all hydrogen
      atoms at the protophilic center with methyl substituents. This study was
      conducted using zeroth-order regular approximation relativistic density
      functional theory (DFT) at the BP86/QZ4P//BP86/TZ2P level. The trends are
      interpreted in terms of the steric effects of methyl substituents at the
      protophilic center of the anionic (Me(m)XH(n-1-m)(-)) and neutral bases
      (Me(m)XH(n-m)). Besides insight, this work also provides an intrinsically
      consistent set of values of the 298 K tert-butyl cation affinities of all
      (partially) methyl-substituted or unsubstituted bases constituted by maingroup
      element hydrides of groups 14-16 in anionic cases (Me(m)XH(n-1-m)(-)) and groups
      15-17 in neutral ones (Me(m)XH(n-m)) along periods 2-6. The effect of long-range
      dispersion (van der Waals) interactions was estimated through dispersion
      corrected density functional theory (DFT-D3) at the BP86-D3/QZ4P//BP86/TZ2P
      level.

PMID- 21718013
TI  - Analysis of the effects of N-substituents on some aspects of the aromaticity of
      imidazoles and pyrazoles.
AB  - The influence of the N-substituent on the aromaticity of azoles is a subject that
      has not yet been addressed in detail, in contrast to the good understanding of
      the corresponding C-substitution. In the present work, we analyze the
      aromaticities of a series of 1,2- and 1,3-azoles (pyrazoles and imidazoles,
      respectively) with the N-substituents NH(2), OH, Cl, SH, H, NO(2), CN, SO(2)F,
      SO(2)CF(3), and N(SO(2)CF(3))(2), which are also compared with the aromaticities
      of the corresponding substituted benzene series. The larger stabilitiy of the
      imidazole ring is due not to a higher aromaticity, but rather to the weakness of
      the N-N bond in the pyrazole series. The aromaticity of azoles was found to be
      significantly less robust to N-substitutions than that of their C-substituted
      benzene counterparts.

PMID- 21718014
TI  - Kinetics and mechanism of OH oxidation of small organic dicarboxylic acids in
      ice: comparison to behavior in aqueous solution.
AB  - To better understand the oxidation of organic species by OH within frozen
      solutions, experiments were conducted with a simplified model system consisting
      of succinic acid (2.5, 5, and 10 mM), using H(2)O(2) (30 mM) as a condensed-phase
      OH precursor. Frozen (-20  degrees C) and aqueous (0  degrees C and room
      temperature) solutions were irradiated using a xenon arc lamp to study the
      differences between frozen and nonfrozen reaction media. Formation of products
      and decay of reactants were measured using ion chromatography (IC) and gas
      chromatography-mass spectrometry (GC-MS). Malonic acid was observed as the
      dominant product, with malic acid formed in significantly smaller amounts, in
      both frozen and unfrozen substrates, suggesting a common mechanism independent of
      phase. Notably, a large decrease was observed in the succinic acid first-order
      decay rate constant when moving from aqueous to frozen samples. This is due not
      to temperature-dependent second-order kinetics or different OH production rates
      between the samples, but instead probably arises from physical separation of the
      succinic acid and H(2)O(2) upon freezing or precipitation of succinic acid upon
      freeze concentration. The effect is not nearly as pronounced for the decay
      kinetics of a much more soluble species, namely, malonic acid. From an
      environmental perspective, this work is the first experimental demonstration that
      dicarboxylic acids present in the cryosphere might be subject to photochemical
      degradation into smaller organic acids and carbon dioxide.

PMID- 21718015
TI  - Gas-phase Raman spectra and the potential energy function for the internal
      rotation of 1,3-butadiene and its isotopologues.
AB  - The gas-phase Raman spectra of 1,3-butadiene and its 2,3-d(2), 1,1,4,4-d(4), and 
      d(6) isotopologues have been recorded with high sensitivity in the region below
      350 cm(-1) in order to investigate the internal rotation (torsional) vibration.
      Based on more accurate structural information, the internal rotor constants F(n)
      were calculated as a function of rotation angle (phi). The data for all the
      isotopologues were then fit using a one-dimensional potential energy function of
      the form V = (1)/(2)?V(n)(1 - cos phi). Initial V(n) values were based on those
      generated from theoretical calculations. The agreement between observed and
      calculated frequencies is very good, although bands not taken into account were
      present in the spectra. The energy difference between the trans and gauche forms
      was determined to be about 1030 cm(-1) (2.94 kcal/mol), and the barrier between
      the two equivalent gauche forms was determined to be about 180 cm(-1) (0.51
      kcal/mol), which agrees well with high-level ab initio calculations. An
      alternative set of assignments also fits the data quite well for all of the
      isotopologues. For this model, the energy difference between the trans and gauche
      forms is about 1080 cm(-1) (3.09 kcal/mol), and the barrier between gauche forms
      is about 405 cm(-1) (1.16 kcal/mol).

PMID- 21718016
TI  - Intracellular protein target detection by quantum dots optimized for live cell
      imaging.
AB  - Imaging of specific intracellular target proteins in living cells has been of
      great challenge and importance for understanding intracellular events and
      elucidating various biological phenomena. Highly photoluminescent and water
      soluble semiconductor nanocrystal quantum dots (QDs) have been extensively
      applied to various cellular imaging applications due to the long-term
      photostability and the tunable narrow emission spectra with broad excitation.
      Despite the great success of various bioimaging and diagnostic applications,
      visualization of intracellular targets in live cells still has been of great
      challenge. Nonspecific binding, difficulty of intracellular delivery, or
      endosomal trapping of nanosized QDs are the main reasons to hamper specific
      target binding in live cells. In this context, we prepared the polymer-coated QDs
      (pcQD) of which the surface was optimized for specific intracellular targeting in
      live cells. Efficient intracellular delivery was achieved through PEGylation and
      subsequent cell penetrating peptide (i.e., TAT) conjugation to the pcQD in order
      to avoid significant endosomal sequestration and to facilitate internalization of
      the QDs, respectively. In this study, we employed HEK293 cell line overexpressing
      endothelin A receptor (ET(A)R), a family of G-protein coupled receptor (GPCR), of
      which the cytosolic c-terminal site is genetically engineered to possess green
      fluorescent protein (GFP) as our intracellular protein target. The fluorescence
      signal of the target protein and the well-defined intracellular behavior of the
      GPCR help to evaluate the targeting specificity of QDs in living cells. To test
      the hypothesis that the TAT-QDs conjugated with antibody against intracellular
      target of interest can find the target, we conjugated anti-GFP antibody to TAT
      PEG-pcQD using heterobifunctional linkers. Compared to the TAT-PEG-pcQD, which
      was distributed throughout the cytoplasm, the antiGFP-functionalized TAT-PEG-pcQD
      could penetrate the cell membrane and colocalize with the GFP. An agonist
      (endothelin-1, ET-1) treatment induced GFP-ET(A)R translocation into
      pericentriolar region, where the GFP also significantly colocalized with antiGFP
      TAT-PEG-pcQD. These results demonstrate that stepwise optimization of PEG-pcQD
      conjugation with both a cell penetrating peptide and an antibody against a target
      of interest allows specific binding to the intracellular target protein with
      minimized nonspecific binding.

PMID- 21718017
TI  - Matrix infrared spectroscopic and theoretical investigations of uranium atom and
      methanol reaction products.
AB  - Reactions of laser-ablated uranium atoms and methanol are investigated in solid
      argon using matrix isolation and infrared spectroscopy. Four new product
      molecules are identified with the help of isotopically substituted methanol as
      well as density functional frequency calculations. Uranium atoms react
      spontaneously with methanol on annealing to form the U(II) insertion product
      CH(3)OUH, which has a quintet ground state with strong C-O and U-H stretching
      vibrations. Further sample annealing allows the reaction of CH(3)OUH and another
      methanol molecule to eliminate H(2) and give the U(OCH(3))(2) product. Near-UV
      vis irradiation isomerizes the CH(3)OUH molecule to the 32 kcal/mol lower energy
      U(IV) CH(3)U(O)H isomer and the U(OCH(3))(2) molecule to the 28 kcal/mol lower
      energy CH(3)OU(O)CH(3) isomer. Both U(IV) products have triplet ground states,
      U?O double bonds, and pyramidal skeletal structures.

PMID- 21718018
TI  - Dihydrogen activation by frustrated carbene-borane Lewis pairs: an experimental
      and theoretical study of carbene variation.
AB  - A variety of Lewis acid-base pairs consisting of tris(pentafluorophenyl)borane,
      B(C(6)F(5))(3), in combination with sterically demanding five- and six-membered N
      heterocyclic carbenes (NHCs) of the imidazolin-2-ylidene, imidazolidin-2-ylidene,
      and tetrahydropyrimidin-2-ylidene types were investigated with respect to their
      potential to act as frustrated Lewis pairs (FLP) by reaction with dihydrogen
      (H(2)) and tetrahydrofuran (THF). A sufficient degree of "frustration" was
      usually established by introduction of a 1,3-di-tert-butyl or 1,3-diadamantyl
      carbene substitution pattern, which allows an unquenched acid-base reactivity and
      thus leads to heterolytic dihydrogen activation and ring-opening of THF. In
      contrast, 1,3-bis(2,6-diisopropylphenyl)-substituted carbenes showed ambiguous
      behavior, and the corresponding five-membered imidazolin-2-ylidene formed a
      stable carbene-B(C(6)F(5))(3) adduct, whereas fast C-F activation and formation
      of a zwitterionic pyrimidinium-fluoroborate was observed for the six-membered
      tetrahydropyrimidin-2-ylidene. A stable adduct was also isolated for the
      combination of the acyclic carbene bis(diisopropylamino)methylene with
      B(C(6)F(5))(3), and consequently no reactivity toward H(2) and THF was observed.
      To rationalize the reactivity of the carbene-borane Lewis pairs, the
      thermodynamics of adduct formation with B(C(6)F(5))(3) were calculated for 10
      different carbenes; the stability (or instability) of these adducts can be used
      as a good measure of the degree of "frustration".

PMID- 21718019
TI  - Structural models of the [Fe4S4] clusters of homologous nitrogenase Fe proteins.
AB  - The iron (Fe) proteins of molybdenum (Mo)-, vanadium (V)-, and iron (Fe)-only
      nitrogenases are encoded by nifH, vnfH, and anfH, respectively. While the nifH
      encoded Fe protein has been extensively studied over recent years, information
      regarding the properties of the vnfH- and anfH-encoded Fe proteins has remained
      scarce. Here, we present a combined biochemical, electron paramagnetic resonance
      (EPR) and X-ray absorption spectroscopy (XAS) analysis of the [Fe(4)S(4)]
      clusters of NifH, VnfH, and AnfH of Azotobacter vinelandii . Our data show that
      all three Fe proteins contain [Fe(4)S(4)] clusters of very similar spectroscopic
      and geometric structural properties, although NifH differs more from VnfH and
      AnfH with regard to the electronic structure. These observations have an
      interesting impact on the theory of the plausible sequence of evolution of
      nitrogenase Fe proteins. More importantly, the results presented herein provide a
      platform for future investigations of the differential activities of the three Fe
      proteins in nitrogenase biosynthesis and catalysis.

PMID- 21718020
TI  - Ultrasmall silver nanopores fabricated by femtosecond laser pulses.
AB  - Ultrasmall nanopores in silver thin films with a diameter of about 2 nm have been
      fabricated using femtosecond laser ablation in liquid. Ultrafast laser pulse
      ablation generates highly nonequilibrium excitated states, from which silver thin
      films emerge and progressively grow with the assistance of capping agent
      molecules. During this growth process, capping agent molecules are enclaved
      within the film, leaving individual ultrasmall pores in the thin film. Our first
      principles calculations show that the pore size is critically determined by the
      dimension of the confined molecules. Our approach advances the capability of
      optical methods in making nanoscale structures with potential applications in
      areas such as near-field aperture probes, imaging masks, magnetic plasmonic
      resonances, and biosensing with individual nanopores.

PMID- 21718021
TI  - Preventing the formation of the long-lived colored transoid-trans photoisomer in
      photochromic benzopyrans.
AB  - A new photochromic fused benzopyran presenting a bridge between the pyran double
      bond and the benzenic ring was prepared. While the UV irradiation of usual
      benzopyrans leads to the formation of two colored photoisomers with very
      different thermal stabilities, studies by laser flash photolysis showed that the
      presence of this particular bridge prevents the formation of the undesirable long
      lived colored TT isomer and therefore after laser irradiation the colored
      solution fades following a fast monoexponential decay.

PMID- 21718022
TI  - A personal nanoparticle respiratory deposition (NRD) sampler.
AB  - A lightweight (60 g), personal nanoparticle respiratory deposition (NRD) sampler
      was developed to selectively collect particles smaller than 300 nm similar to
      their typical deposition in the respiratory tract. The sampler operates at 2.5
      Lpm and consists of a respirable cyclone fitted with an impactor and a diffusion
      stage containing mesh screens. The cut-point diameter of the impactor was
      determined to be 300 nm with a sharpness sigma = 1.53. The diffusion stage
      screens collect particles with an efficiency that matches the deposition
      efficiency of particles smaller than 300 nm in the respiratory tract. Impactor
      separation performance was unaffected by loading at typical workplace levels (p
      value = 0.26). With chemical analysis of the diffusion media, the NRD sampler can
      be used to directly assess exposures to nanoparticles of a specific composition
      apart from other airborne particles. The pressure drop of the NRD sampler is
      sufficiently low to permit its operation with conventional, belt-mounted sampling
      pumps.

PMID- 21718023
TI  - Antibacterial fluorinated silica colloid superhydrophobic surfaces.
AB  - A superhydrophobic xerogel coating synthesized from a mixture of nanostructured
      fluorinated silica colloids, fluoroalkoxysilane, and a backbone silane is
      reported. The resulting fluorinated surface was characterized using contact angle
      goniometry, scanning electron microscopy (SEM), and atomic force microscopy
      (AFM). Quantitative bacterial adhesion studies performed using a parallel plate
      flow cell demonstrated that the adhesion of Staphylococcus aureus and Pseudomonas
      aeruginosa was reduced by 2.08 +/- 0.25 and 1.76 +/- 0.12 log over controls,
      respectively. This simple superhydrophobic coating synthesis may be applied to
      any surface, regardless of geometry, and does not require harsh synthesis or
      processing conditions, making it an ideal candidate as a biopassivation strategy.

PMID- 21718024
TI  - Electrochemically addressed cross-links in polyelectrolyte multilayers: cyclic
      duravoltammetry.
AB  - In situ nanoindentation was performed on a multilayer of poly(acrylic acid) and a
      high molecular weight, pendant chain polyviologen under controlled
      electrochemical potential. The modulus of the thin film of polyelectrolyte
      complex was reversibly modulated, by about an order of magnitude, upon changing
      the state of charge within the material using the electrochemically active and
      addressable viologen repeat units. The applied potential, under aqueous
      conditions, is believed to control the extent of cross-link formation.
      Simultaneous quartz crystal microbalance measurements revealed the flux of ions
      into or out of the multilayer during redox cycling. Apparent film modulus also
      depends on the identity of the last layer.

PMID- 21718025
TI  - Platinum-catalyzed diastereoselective intramolecular coupling of allyl halides
      and hydrazones.
AB  - Nucleophilic allyl platinum addition to hydrazones under platinum-catalyzed
      conditions was studied. To generate nucleophilic allyl platinum complexes, allyl
      halides were employed with platinum complexes, SnCl(2), and H(2). The allyl
      platinum(IV) intermediates reacted with the hydrazone to give the corresponding
      cyclic amine derivatives in good yield and with excellent diastereoselectivity.
      The cis selectivity of N-tethered substrates was attributed to a tight
      interaction of allyl platinum species with the hydrazone, on the basis of the
      results of solvent screening and acid/base addition experiments.

PMID- 21718026
TI  - Thermoresponsive polypeptides from pegylated poly-L-glutamates.
AB  - The synthesis and characterization of new thermoresponsive pegylated poly-L
      glutamate (poly-L-EG(x)Glu) are described. The obtained polypeptides display low
      critical solution temperature (LCST) behaviors in water, and the LCST can be
      tuned via copolymerization of different amino acid monomers at varied molar
      ratio. This is the first example of thermoresponsive polypeptide made from ring
      opening polymerization of alpha-amino acid N-carboxyanhydrides (NCAs). Circular
      dichroism characterizations reveal that the secondary structure of poly-L
      EG(x)Glu depended on the chain length of the side chain.

PMID- 21718027
TI  - Inherent charge-shifting polyelectrolyte multilayer blends: a facile route for
      tunable protein release from surfaces.
AB  - Recent research has highlighted degradable multilayer films that enable the
      programmed release of different therapeutics. Multilayers constructed by the
      layer-by-layer (LbL) deposition that can undergo disassembly have been
      demonstrated to be of considerable interest, particularly for biomedical surface
      coatings due to their versatility and mild aqueous processing conditions,
      enabling the inclusion of biologic drugs with high activity. In this study, we
      examine the controlled release of a protein using a different mechanism for film
      disassembly, the gradual dissociation of film interactions under release
      conditions. Poly(beta-amino ester)s and poly(L-lysine) (PLL) were used as the
      positively charged multilayer components coassembled with a model negatively
      charged antigen protein, ovalbumin (Ova). The release of the protein from these
      multilayer films is dominated by the slow shift in the charge of components under
      physiological pH conditions rather than by hydrolytic degradative release. The
      time scale of release can be varied over almost 2 orders of magnitude by varying
      the ratio of the two polyamines in the deposition solution. The highly versatile
      and tunable properties of these films form a basis for designing controlled and
      sequential delivery of drug coatings using a variety of polyions.

PMID- 21718028
TI  - Role of water state and mobility on the antiplasticization of green and roasted
      coffee beans.
AB  - The effect of water on "antiplasticization" and plasticization of green and
      roasted coffee was studied by textural analysis, sorption isotherms, differential
      scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). From BET
      monolayer value to a(w) = 0.61 and 0.75 for green and roasted coffee,
      respectively, the solid matrix hydration occurred and water induced hardening.
      Very short NMR T(2) values and the concomitant absence of any DSC endothermic
      peak assignable to water freezing were observed at these a(w) values. When solid
      matrix hydration was completed, water started to act as a plasticizing agent, the
      compressive modulus started to decrease, and NMR revealed the appearance of a new
      proton pool with increased mobility. According to DSC, only when the plasticizing
      effect became important did water present enough mobility to freeze. Above this
      moisture value (a(w) = 0.78 and 0.86 for green and roasted coffee, respectively),
      water determined a decrease of bean hardness and a further decrease of the
      elastic modulus.

PMID- 21718029
TI  - Antitumor actinopyranones produced by Streptomyces albus POR-04-15-053 isolated
      from a marine sediment.
AB  - Four new antitumor pyranones, PM050511 (1), PM050463 (2), PM060054 (3), and
      PM060431 (4), were isolated from the cell extract of the marine-derived
      Streptomyces albus POR-04-15-053. Their structures were elucidated by a
      combination of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS. They
      consist of an alpha-methoxy-gamma-pyrone ring containing a highly substituted
      tetraene side chain glycosylated at C-10 in the case of 1 and 4. Compounds 1 and
      4 displayed strong cytotoxicity against three human tumor cell lines with GI50
      values in the submicromolar range, whereas 2 showed subnanomolar activity as an
      inhibitor of EGFR-MAPK-AP1-mediated mitogenic signaling, causing inhibition of
      EGF-mediated AP1 trans-activation and EGF-mediated ERK activation and slight
      inhibition of EGF-mediated JNK activation. Taken together, these results suggest
      that members of the pyranone family of compounds could be developed as potential
      antitumor agents.

PMID- 21718030
TI  - Exploring the reactions of beta-amyloid (Abeta) peptide 1-28 with Al(III) and
      Fe(III) ions.
AB  - The reactions of human beta-amyloid peptide 1-28 (Abeta28) with Al(III) and
      Fe(III) ions were investigated by (1)H NMR and electrospray ionization mass
      spectrometry (ESI-MS) under pH conditions close to physiological ones. (1)H NMR
      titrations, performed in the 5.3-8.0 pH range, revealed that no measurable
      amounts of Abeta28-Al(III) or Abeta28-Fe(III) adducts are formed; such metal
      adducts could not be obtained even by changing a number of experimental
      conditions, e.g., temperature, buffer, nature of the salt, etc. These
      observations were later confirmed by ESI-MS. It is thus demonstrated that
      Abeta28, at physiological pH, is not able to form binary complexes with Al(III)
      and Fe(III) ions of sufficient stability to compete with metal hydroxide
      precipitation. The biological implications of these findings are discussed in the
      frame of current literature.

PMID- 21718031
TI  - Sesquiterpene and xanthone derivatives from the sea fan-derived fungus
      Aspergillus sydowii PSU-F154.
AB  - Three new sesquiterpenes, named aspergillusenes A and B and (+)-(7S)-7-O
      methylsydonic acid, and two new hydrogenated xanthone derivatives, named
      aspergillusones A and B, were isolated from the sea fan-derived fungus
      Aspergillus sydowii PSU-F154 together with 10 known compounds. Their structures
      were identified on the basis of spectroscopic data. The isolated compounds were
      evaluated for their antioxidant activity.

PMID- 21718032
TI  - Synthesis, structure, and magnetic properties of three 1D chain complexes based
      on high-spin metal-cyanide clusters: [Mn(III)6M(III)] (M = Cr, Fe, Co).
AB  - On the basis of high-spin metal-cyanide clusters of Mn(III)(6)M(III) (M = Cr, Fe,
      Co), three one-dimensional (1D) chain complexes,
      [Mn(salen)](6)[Cr(CN)(6)](2).6CH(3)OH.H(2)O (1), [Mn(5
      CH(3))salen)](6)[Fe(CN)(6)](2).2CH(3)CN.10H(2)O (2), and [Mn(5
      CH(3))salen)](6)[Co(CN)(6)](2).2CH(3)CN.10H(2)O (3) [salen = N,N'
      ethylenebis(salicylideneiminato) dianion], have been synthesized and
      characterized structurally as well as magnetically. Complexes 2 and 3 are
      isomorphic but slightly different from complex 1. All three complexes contain a
      1D chain structure which is comprised of alternating high-spin metal-cyanide
      clusters of [Mn(6)M](3+) and a bridging group [M(CN)(6)](3-) in the trans mode.
      Furthermore, the three complexes all exhibit extended 3D supramolecular networks
      originating from short intermolecular contacts. Magnetic investigation indicates
      that the coupling mechanisms are intrachain antiferromagnetic interactions for 1
      and ferromagnetic interactions for 2, respectively. Complex 3 is a magnetic
      dilute system due to the diamagnetic nature of Co(III). Further magnetic
      investigations show that complexes 1 and 2 are dominated by the 3D
      antiferromagnetic ordering with T(N) = 7.2 K for 1 and 9.5 K for 2. It is worth
      noting that the weak frequency-dependent phenomenon of AC susceptibilities was
      observed in the low-temperature region in both 1 and 2, suggesting the presence
      of slow magnetic relaxations.

PMID- 21718033
TI  - Stilbenes and tyrosol as target compounds in the assessment of antioxidant and
      hypolipidemic activity of Vitis vinifera red wines from southern Brazil.
AB  - The contents of stilbene monomers, cis-resveratrol, trans-resveratrol, cis
      piceid, trans-piceid, and tyrosol, were quantified in Vitis vinifera red wines,
      cvs. Cabernet Franc, Merlot, Sangiovese, and Syrah, 2006 and 2007 vintages, from
      the Sao Joaquim region, a new grape-growing region at southern Brazil. Moreover,
      the effect of chronic consumption of these wines on the antioxidant and
      hypolipidemic activities was monitored in C57BL6 LDL receptor knockout mice and
      treated with a hypercholesterolemic diet. Red wines from this region had
      substantial levels of resveratrols (the predominant forms were glycoside and
      trans) and tyrosol. Biomonitoring of antioxidant and hypolipidemic activities in
      vivo revealed that consumption of these wines increased the antioxidant capacity
      and reduced the hypercholesterolemia and hypertriglyceridemia promoted by the
      hypercholesterolemic diet. Significant correlations were found between the
      increase of antioxidant capacity markers, the decrease of lipid levels promoted
      by wine consumption, and the contents of stilbenes and tyrosol, supporting the
      important biological activity of these compounds.

PMID- 21718034
TI  - Oil-in-water monitoring using membrane inlet mass spectrometry.
AB  - A membrane inlet mass spectrometry (MIMS) system has been used for detection and
      analysis of two types of North Sea crude oil. The system was installed on-field
      on the Flotta Oil Terminal (Orkney, UK). It consisted of a quadrupole mass
      spectrometer (QMS) connected to the capillary probe with a silicone-based
      membrane. The produced mass spectra and calibration plots from the MIMS
      instrument showed the capability to measure levels of individual hydrocarbons
      within crude oil in seawater. The generated mass spectra from the field tests
      also showed the ability to distinguish between different types of oil and to
      determine concentrations of toxic hydrocarbons in oil (e.g., benzene, toluene,
      and xylene (BTX)). The performance of the instrument at different temperatures of
      seawater and oil droplet sizes was also investigated. The results showed that the
      QMS-based MIMS system has a potential to complement existing oil-in-water (OiW)
      monitors by being able to detect different oil types and specific hydrocarbon
      concentrations with high accuracy, which are currently not supported in
      commercially available OiW monitors.

PMID- 21718035
TI  - Copper/DIPEA-catalyzed, aldehyde-induced tandem decarboxylation-coupling of
      natural alpha-amino acids and phosphites or secondary phosphine oxides.
AB  - A copper/DIPEA-catalyzed, aldehyde-induced intermolecular decarboxylative
      coupling reaction of natural alpha-amino acids and phosphites or secondary
      phosphine oxides was developed. In this process, a series of potentially useful
      ligands for organic synthesis and biologically important unnatural amino acid
      derivatives (tertiary amino phosphorus compounds) were obtained.

PMID- 21718036
TI  - Solvation structure and stability of [(CH3)2NH]m(NH3)n-H hypervalent clusters:
      ionization potentials and switching of hydrogen-atom localized site.
AB  - Ionization potentials (IPs) of [(CH(3))(2)NH](m)(NH(3))(n)-H hypervalent radical
      clusters produced by an ArF excimer laser photolysis of dimethylamine (DMA)
      ammonia mixed clusters are determined by the photoionization threshold
      measurements. The IPs of the DMA(1)(NH(3))(n)-H hypervalent radicals decrease
      rapidly with the number of ammonia up to n=4, and then its decrease rate becomes
      much slower for n >= 5. This trend is very similar to that found for
      NH(4)(NH(3))(n) clusters. The calculated results on the stable structures and IP
      as well as the observed IP for DMA(1)(NH(3))(n)-H indicate that the hydrogen atom
      localized site is the NH(3) moiety for n=1, while the doubly coordinated DMA-H is
      favorable for n=2-4, and then 4-fold-coordinated NH(4) is again more stable for n
      >= 5. These changes are consistent with the results on the femtosecond pump-probe
      experiments of DMA(n)-H clusters. Switching of the hydrogen atom-localized site
      is ascribed to the instability of DMA-H against a hydrogen-atom dissociation.

PMID- 21718037
TI  - 2-Chloroethylisocyanate. Thermal decomposition and spectroscopic properties.
AB  - 2-Chloroethylisocyanate has been studied in a thorough way. NMR, Raman, FTIR, and
      Ar-matrix vibrational spectra of the molecule are presented and discussed with
      the complement of ab initio and DFT methods. The spectroscopic results reveal the
      existence of anti and gauche conformers that are equally populated in the gas
      phase. Thermal decomposition between 393 and 648 K shows two different pathways
      depending on the temperature, which can be interpreted in terms of simple second-
      and first-order mechanisms, respectively. Quantum mechanical calculations
      reproduce the experimental results.

PMID- 21718038
TI  - Ni(II) salts and 2-propanol effect catalytic reductive coupling of epoxides and
      alkynes.
AB  - A Ni-catalyzed reductive coupling of alkynes and epoxides using Ni(II) salts and
      simple alcohol reducing agents is described. Whereas previously reported
      conditions relied on Ni(cod)(2) and Et(3)B, this system has several advantages
      including the use of air-stable and inexpensive Ni(II) precatalysts (e.g.,
      NiBr(2).3H(2)O) as the source of Ni(0) and simple alcohols (e.g., 2-propanol) as
      the reducing agent. Deuterium-labeling experiments are consistent with oxidative
      addition of an epoxide C-O bond that occurs with inversion of configuration.

PMID- 21718039
TI  - Copper-catalyzed oxidative direct cyclization of N-methylanilines with electron
      deficient alkenes using molecular oxygen.
AB  - The oxidative direct cyclizaion of N-methylanilines with electron-deficient
      alkenes involving maleimides and benzylidene malononitriles through sp(3) and
      sp(2) C-H bond cleavage proceeds effectively under a CuCl(2)/O(2) catalysis to
      provide the corresponding tetrahydroquinolines in good yields.

PMID- 21718040
TI  - Deep-UV resonance Raman analysis of the Rhodobacter capsulatus cytochrome
      bc1complex reveals a potential marker for the transmembrane peptide backbone.
AB  - Classical strategies for structure analysis of proteins interacting with a lipid
      phase typically correlate ensemble secondary structure content measurements with
      changes in the spectroscopic responses of localized aromatic residues or reporter
      molecules to map regional solvent environments. Deep-UV resonance Raman (DUVRR)
      spectroscopy probes the vibrational modes of the peptide backbone itself, is very
      sensitive to the ensemble secondary structures of a protein, and has been shown
      to be sensitive to the extent of solvent interaction with the peptide backbone [
      Wang , Y. , Purrello , R. , Georgiou , S. , and Spiro , T. G. ( 1991 ) J. Am.
      Chem. Soc. 113 , 6368 - 6377 ]. Here we show that a large detergent solubilized
      membrane protein, the Rhodobacter capsulatus cytochrome bc(1) complex, has a
      distinct DUVRR spectrum versus that of an aqueous soluble protein with similar
      overall secondary structure content. Cross-section calculations of the amide
      vibrational modes indicate that the peptide backbone carbonyl stretching modes
      differ dramatically between these two proteins. Deuterium exchange experiments
      probing solvent accessibility confirm that the contribution of the backbone
      vibrational mode differences are derived from the lipid solubilized or
      transmembrane alpha-helical portion of the protein complex. These findings
      indicate that DUVRR is sensitive to both the hydration status of a protein's
      peptide backbone, regardless of primary sequence, and its secondary structure
      content. Therefore, DUVRR may be capable of simultaneously measuring protein
      dynamics and relative water/lipid solvation of the protein.

PMID- 21718041
TI  - Emissions of PCDD/Fs, PCBs, and PAHs from a modern diesel engine equipped with
      catalyzed emission control systems.
AB  - Exhaust emissions of 17 2,3,7,8-substituted chlorinated dibenzo-p-dioxin/furan
      (CDD/F) congeners, tetra-octa CDD/F homologues, 12 2005 WHO chlorinated biphenyls
      (CB) congeners, mono-nona CB homologues, and 19 polycyclic aromatic hydrocarbons
      (PAHs) from a model year 2008 Cummins ISB engine were investigated. Testing
      included configurations composed of different combinations of aftertreatment
      including a diesel oxidation catalyst (DOC), catalyzed diesel particulate filter
      (CDPF), copper zeolite urea selective catalytic reduction (SCR), iron zeolite
      SCR, and ammonia slip catalyst. Results were compared to a baseline engine out
      configuration. Testing included the use of fuel that contained the maximum
      expected chlorine (Cl) concentration of U.S. highway diesel fuel and a Cl level
      1.5 orders of magnitude above. Results indicate there is no risk for an increase
      in polychlorinated dibenzo-p-dioxin/furan and polychlorinated biphenyl emissions
      from modern diesel engines with catalyzed aftertreatment when compared to engine
      out emissions for configurations tested in this program. These results, along
      with PAH results, compare well with similar results from modern diesel engines in
      the literature. The results further indicate that polychlorinated dibenzo-p
      dioxin/furan emissions from modern diesel engines both with and without
      aftertreatment are below historical values reported in the literature as well as
      the current inventory value.

PMID- 21718042
TI  - Synthesis, molecular and electronic structures of six-coordinate transition metal
      (Mn, Fe, Co, Ni, Cu, and Zn) complexes with redox-active 9-hydroxyphenoxazin-1
      one ligands.
AB  - A series of pseudo-octahedral metal (M = Mn, Fe, Co, Ni, Cu, Zn) complexes 4 of a
      new redox-active ligand, 2,4,6,8-tetra(tert-butyl)-9-hydroxyphenoxazin-1-one 3,
      have been synthesized, and their molecular structures determined with help of X
      ray crystallography. The effective magnetic moments of complexes 4 (M = Mn, Fe,
      Co, and Ni) measured in the solid state and toluene solution point to the
      stabilization of their high-spin electronic ground states. Detailed information
      on the electronic structure of the complexes and their redox-isomeric forms has
      been obtained using density functional theory (DFT) B3LYP*/6-311++G(d,p)
      calculations. The energy disfavored low-spin structures of manganese, iron, and
      cobalt complexes have been located, and based on the computed geometries and
      distribution of spin densities identified as Mn(IV)[(Cat-N-SQ)](2), Fe(II)[Cat-N
      BQ)](2), and Co(II)[Cat-N-BQ)](2) compounds, respectively. It has been shown that
      stabilization of the high-spin structures of complexes 4 (M = Mn, Fe, Co) is
      caused by the rigidity of the molecular framework of ligands 3 that sterically
      inhibits interconversions between the redox-isomeric forms of the complexes. The
      calculations performed on complex 4 (M = Co) predict that a suitable structural
      modification that might provide for stabilization of the low-spin electromeric
      forms and create conditions for the valence tautomeric rearrangement via
      stabilization of the low-spin electromer and narrowing energy gap between the low
      spin ground state tautomer and the minimal energy crossing point on the
      intersection of the potential energy surfaces of the interconverting structures
      consists in the replacement of an oxygen in the oxazine ring by a bulkier sulfur
      atom.

PMID- 21718043
TI  - Diverse chemiresistors based upon covalently modified multiwalled carbon
      nanotubes.
AB  - A diverse array of multiwalled carbon nanotube (MWCNT) sensory materials have
      been synthesized and used to create sensors capable of identifying volatile
      organic compounds (VOCs) on the basis of their functional groups. Functionalized
      MWCNTs with a series of cross-sensitive recognition groups were successfully
      synthesized via zwitterionic and post-transformation synthetic procedures. The
      incorporated chemical functional groups on MWCNT surfaces introduced greatly
      increased sensitivity and selectivity to the targeted analytes. The distinct
      response pattern of each chemical was subjected to statistical treatments, which
      led to a clear separation and accurate identification of 100% of the VOCs. These
      results demonstrate that covalent functionalized MWCNT-based sensor arrays are a
      promising approach for low-cost, real time detection and identification of VOCs.

PMID- 21718044
TI  - Biofumigation for control of pale potato cyst nematodes: activity of brassica
      leaf extracts and green manures on Globodera pallida in vitro and in soil.
AB  - The effects of brassica green manures on Globodera pallida were assessed in vitro
      and in soil microcosms. Twelve of 22 brassica accessions significantly inhibited
      the motility of G. pallida infective juveniles in vitro. Green manures of
      selected brassicas were then incorporated into soil containing encysted eggs of
      G. pallida. Their effect on egg viability was estimated by quantifying nematode
      actin 1 mRNA by RT-qPCR. The leaf glucosinolate profiles of the plants were
      determined by high-performance liquid chromatography. Three Brassica juncea lines
      (Nemfix, Fumus, and ISCI99) containing high concentrations of 2-propenyl
      glucosinolate were the most effective, causing over 95% mortality of encysted
      eggs of G. pallida in polyethylene-covered soil. The toxic effects of green
      manures were greater in polyethylene-covered than in open soil. Toxicity in soil
      correlated with the concentration of isothiocyanate-producing glucosinolate but
      not total glucosinolate in green manures.

PMID- 21718045
TI  - Dendrimers as encapsulating, stabilizing, or directing agents for inorganic
      nanoparticles.

PMID- 21718046
TI  - Direct Fmoc-chemistry-based solid-phase synthesis of peptidyl thioesters.
AB  - Attachment of a growing peptide chain to a glycylaminomethyl resin via a
      thioglycinamide bond is compatible with Fmoc-chemistry solid-phase peptide
      synthesis. Subsequent S-alkylation of the thioamide gives a thioimide that, on
      treatment with aqueous trifluoroacetic acid, releases the peptide from the resin
      in the form of a C-terminal thioester.

PMID- 21718047
TI  - Dioxin concentrations in breast milk of Vietnamese nursing mothers: a survey four
      decades after the herbicide spraying.
AB  - In an operation by United States Armed Forces during 1961 to 1971, large
      quantities of herbicides were sprayed in South Vietnam. These herbicides
      contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD), the most toxic
      congener of dioxins. Several decades after the herbicide spraying ceased, dioxin
      concentrations in the environment and human remained elevated in the sprayed
      areas. Breast milk samples from 520 nursing mothers residing in areas including
      the hot spots as well as the sprayed and unsprayed areas were collected to
      quantify the levels of dioxins. The total toxic equivalents of 2,3,7,8-substitued
      PCDDs/PCDFs in breast milk of mothers living in the hot spots, and the sprayed
      and unsprayed areas were 14.10 pg/g lipid, 10.89 pg/g lipid, and 4.09 pg/g lipid
      for primiparae and 11.48 pg/g lipid, 7.56 pg/g lipid, and 2.84 pg/g lipid for
      multiparae, respectively, with significant differences in the values among the
      three areas. In the hot spots, dioxin levels were highly correlated with the
      residency of mothers after adjustment for their age and parity.

PMID- 21718048
TI  - The preparation of (-)-grandisine B from (+)-grandisine D; a biomimetic total
      synthesis or formation of an isolation artefact?
AB  - An efficient new alkyne-acetal cyclization procedure has been developed to
      prepare enantiopure indolizidine building blocks from l-proline and then applied
      to prepare the Elaeocarpus-derived alkaloids grandisine B and grandisine D in an
      efficient manner. However, evidence is presented which indicates that grandisine
      B does not occur naturally but is formed by reaction of grandisine D with ammonia
      during the extraction/purification process.

PMID- 21718049
TI  - First-principles study of rectification in bis-2-(5-ethynylthienyl)ethyne
      molecular junctions.
AB  - Using density functional theory (DFT) combined with the first-principles
      nonequilibrium Green's function (NEGF), we investigated the electron-transport
      properties and rectifying behaviors of several molecular junctions based on the
      bis-2-(5-ethynylthienyl)ethyne (BETE) molecule. To examine the roles of different
      rectification factors, asymmetric electrode-molecule contacts and donor-acceptor
      substituent groups were introduced into the BETE-based molecular junction. The
      asymmetric current-voltage characteristics were obtained for the molecular
      junctions containing asymmetric contacts and donor-acceptor groups. In our
      models, the computed rectification ratios show that the mode of electrode
      molecule contacts plays a crucial role in rectification and that the rectifying
      effect is not enhanced significantly by introducing the additional donor-acceptor
      components for the molecular rectifier with asymmetric electrode-molecule
      contacts. The current-voltage characteristics and rectifying behaviors are
      discussed in terms of transmission spectra, molecular projected self-consistent
      Hamiltonian (MPSH) states, and energy levels of MPSH states.

PMID- 21718050
TI  - Indolequinone inhibitors of NRH:quinone oxidoreductase 2. Characterization of the
      mechanism of inhibition in both cell-free and cellular systems.
AB  - We describe a series of indolequinones as efficient mechanism-based inhibitors of
      NRH:quinone oxidoreductase 2 (NQO2) for use either in cellular or cell-free
      systems. Compounds were designed to be reduced in the active site of the enzyme
      leading to loss of a substituted phenol leaving group and generation of a
      reactive iminium electrophile. Inhibition of NQO2 activity was assessed in both
      cell-free systems and the human leukemia K562 cell line. Inhibition of
      recombinant human NQO2 by the indolequinones was NRH-dependent, with kinetic
      parameters characteristic of mechanism-based inhibition and partition ratios as
      low as 2.0. Indolequinones inhibited NQO2 activity in K562 cells at nanomolar
      concentrations that did not inhibit NQO1 and were nontoxic to cells. Computation
      based molecular modeling simulations demonstrated favorable conformations of
      indolequinones positioned directly above and in parallel with the isoalloxazine
      ring of FAD, and mass spectrometry extended our previous finding of adduction of
      the FAD in the active site of NQO2 by an indolequinone-derived iminium
      electrophile to the wider series of indolequinone inhibitors. Modeling combined
      with biochemical testing identified key structural parameters for effective
      inhibition, including a 5-aminoalkylamino side chain. Hydrogen bonding of the
      terminal amine nitrogen in the aminoalkylamino side chain was found to be
      critical for the correct orientation of the inhibitors in the active site. These
      indolequinones were irreversible inhibitors and were found to be at least 1 order
      of magnitude more potent than any previously documented competitive inhibitors of
      NQO2 and represent the first mechanism-based inhibitors of NQO2 to be
      characterized in cellular systems.

PMID- 21718051
TI  - Structural relaxation of polymer nanospheres under soft and hard confinement:
      isobaric versus isochoric conditions.
AB  - We have measured the glassy-state structural relaxation of aqueous suspended
      polystyrene (PS) nanoparticles (the case of soft confinement) and the
      corresponding silica-capped PS nanoparticles (the case of hard confinement) via
      differential scanning calorimetry. Suspended and capped PS nanoparticles undergo
      physical aging under isobaric and isochoric conditions, respectively. With
      decreasing diameter, suspended and capped PS nanoparticles exhibited reduced and
      bulk glass transition temperatures (T(g)), respectively. To account for T(g)
      changes with confinement, all physical aging measurements were performed at a
      constant value of T(g) - T(a), where T(a) is the aging temperature. With
      decreasing diameter, aqueous suspended PS nanoparticles exhibited enhanced
      physical aging rates in comparison to bulk PS. Due to differences in
      thermodynamic conditions during aging and interfacial effects from
      nanoconfinement, at all values of T(g) - T(a) investigated, capped PS
      nanoparticles aged at reduced rates compared to the corresponding aqueous
      suspended PS nanoparticles. We captured the physical aging behavior of all
      nanoparticles via the Tool, Narayanaswamy, and Moynihan model of structural
      relaxation.

PMID- 21718052
TI  - Cloning and characterization of an 11S legumin, Car i 4, a major allergen in
      pecan.
AB  - Among tree nut allergens, pecan allergens remain to be identified and
      characterized. The objective was to demonstrate the IgE-binding ability of pecan
      11S legumin and characterize its sequential IgE-binding epitopes. The 11S legumin
      gene was amplified from a pecan cDNA library and expressed as a fusion protein in
      Escherichia coli. The native 11S legumin in pecan extract was identified by mass
      spectrometry/mass spectrometry (MS/MS). Sequential epitopes were determined by
      probing the overlapping peptides with three serum pools prepared from different
      patients' sera. A three-dimensional model was generated using almond legumin as a
      template and compared with known sequential epitopes on other allergenic tree nut
      homologues. Of 28 patients tested by dot blot, 16 (57%) bound to 11S legumin,
      designated Car i 4. MS/MS sequencing of native 11S legumin identified 33 kDa
      acidic and 20-22 kDa basic subunits. Both pecan and walnut seed protein extracts
      inhibited IgE binding to recombinant Car i 4, suggesting cross-reactivity with
      Jug r 4. Sequential epitope mapping results of Car i 4 revealed weak, moderate,
      and strong reactivity of serum pools against 10, 5, and 4 peptides, respectively.
      Seven peptides were recognized by all three serum pools, of which two were
      strongly reactive. The strongly reactive peptides were located in three discrete
      regions of the Car i 4 acidic subunit sequence (residues 118-132, 208-219, and
      238-249). Homology modeling of Car i 4 revealed significant overlapping regions
      shared in common with other tree nut legumins.

PMID- 21718053
TI  - Molecular detection of bacterial pathogens using microparticle enhanced double
      stranded DNA probes.
AB  - Rapid, specific, and sensitive detection of bacterial pathogens is essential
      toward clinical management of infectious diseases. Traditional approaches for
      pathogen detection, however, often require time-intensive bacterial culture and
      amplification procedures. Herein, a microparticle enhanced double-stranded DNA
      probe is demonstrated for rapid species-specific detection of bacterial 16S rRNA.
      In this molecular assay, the binding of the target sequence to the fluorophore
      conjugated probe thermodynamically displaces the quencher probe and allows the
      fluorophore to fluoresce. By incorporation of streptavidin-coated microparticles
      to localize the biotinylated probes, the sensitivity of the assay can be improved
      by 3 orders of magnitude. The limit of detection of the assay is as few as eight
      bacteria without target amplification and is highly specific against other common
      pathogens. Its applicability toward clinical diagnostics is demonstrated by
      directly identifying bacterial pathogens in urine samples from patients with
      urinary tract infections.

PMID- 21718054
TI  - Chemical constituents of a marine fungus, Arthrinium sacchari.
AB  - Three new diterpenes, myrocin D (1), libertellenone E (2), and libertellenone F
      (3), and a new isocoumarin, decarboxyhydroxycitrinone (4), were isolated from the
      marine fungus Arthrinium sacchari, together with three known compounds (5-7). The
      structures of 1-4 were elucidated from spectroscopic data (NMR, MS, IR), and the
      absolute configurations of 1-3 were determined by X-ray diffraction analysis. The
      antiangiogenic activity of these compounds was evaluated by measuring their
      antiproliferation effects on human umbilical vein endothelial cells (HUVECs) and
      human umbilical artery endothelial cells (HUAECs). Compounds 4-7 showed
      inhibitory activity.

PMID- 21718056
TI  - Organocatalytic asymmetric Strecker reaction of di- and trifluoromethyl
      ketoimines. Remarkable fluorine effect.
AB  - A highly enantioselective Strecker reaction of difluoromethyl and trifluoromethyl
      ketoimines was developed. Remarkable fluorine effect on the reactivity and
      selectivity is observed and discussed.

PMID- 21718055
TI  - Regioselective synthesis of water-soluble monophosphate derivatives of
      combretastatin A-1.
AB  - The natural products combretastatin A-4 (CA4) and combretastatin A-1 (CA1) are
      potent cancer vascular disrupting agents and inhibitors of tubulin assembly (IC50
      = 1-2 MUM). The phosphorylated prodrugs CA4P and CA1P are undergoing human
      clinical trials against cancer. CA1 is unique due to its incorporation of a
      vicinal phenol, which has afforded the opportunity to prepare both diphosphate
      and regioisomeric monophosphate derivatives. Here, we describe the first
      synthetic routes suitable for the regiospecific preparation of the CA1
      monophosphates CA1MPA (8a/b) and CA1MPB (4a/b). The essential regiochemistry
      necessary to distinguish between the two vicinal phenolic groups was accomplished
      with a tosyl protecting group strategy. Each of the four monophosphate analogues
      (including Z and E isomers) demonstrated in vitro cytotoxicity against selected
      human cancer cell lines comparable to their corresponding diphosphate congeners.
      Furthermore, Z-CA1MPA (8a) and Z-CA1MPB (4a) were inactive as inhibitors of
      tubulin assembly (IC50 > 40 MUM), as anticipated in this pure protein assay.

PMID- 21718057
TI  - Methylenecyclopropanes in [4+1] cycloaddition with enones.
AB  - A nickel-catalyzed [4+1] cycloaddition of enones with methylenecyclopropanes
      leading to dihydrofurans was developed. The reaction outcome is attributed to the
      transformation of methlenecyclopropane, which is incorporated into a five
      membered ring as a one-carbon fragment.

PMID- 21718058
TI  - Theoretical study on the regioselectivity of the B80 buckyball in electrophilic
      and nucleophilic reactions using DFT-based reactivity indices.
AB  - Density functional theory calculations at the B3LYP/SVP and B3LYP/6-311G(d)
      levels were carried out for a series of XH(3)B(80) complexes with X = {N, P, As,
      B, Al}. To probe the regioselectivity of B(80), the electronic Fukui function,
      the molecular electrostatic potential (MEP), and the natural bond orbital (NBO)
      were determined. These indices were shown to provide reliable guides to predict
      the relative reactivities of the boron buckyball sites. Thermodynamic stabilities
      of the complexes formed by the reaction of B(80) with nucleophiles (NH(3), PH(3),
      AsH(3)) and electrophiles (BH(3), AlH(3)) are in good agreement with the
      prediction of regioselectivity indicated on the basis of Fukui and MEP indices.
      The qualitative results suggest the boron buckyball to be an amphoteric and hard
      molecule. It has two distinct reactive sites localized on caps and frame, which
      act as acids and bases, respectively. Most of the complexes are stable with
      formation energies comparable to that of the analogous complexes of the borane
      molecule, BH(3)BH(3), BH(3)NH(3), and BH(3)AlH(3). The B-H-B bond characteristics
      of diborane are recovered in B(80)BH(3). Exohedral complexes are more stable than
      endohedral complexes. The most stable complexes are those with NH(3) on the caps
      and BH(3) on the pentagonal ring of B(80).

PMID- 21718059
TI  - Vesicles in ionic liquids.
AB  - The formation of vesicles from 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine
      (DPPC) in several room-temperature ionic liquids, namely, 1-butyl-3
      methylimidazolium tetrafluoroborate (BmimBF(4)), 1-butyl-3-methylimidazolium
      hexafluorophosphate (BmimPF(6)), 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide (EmimNTf(2)), and N-benzylpyridinium
      bis(trifluoromethylsulfonyl)imide (BnPyNTf(2)), as well as in a water/BmimBF(4)
      mixture, was investigated. In pure ionic liquids, observations by staining
      transmission electron microscopy demonstrated clearly the formation of spherical
      structures with diameters of 200-400 nm. The morphological characteristics of
      these vesicles in ionic liquids, in particular, the membrane thicknesses, were
      first investigated by small-angle neutron scattering measurements. The mean
      bilayer thickness was found to be ~63 +/- 1 A in a deuterated ionic liquid
      (BnPyNTf(2)-d). This value was similar to that observed in water. The effect of
      ILs on the modification of the phase physical properties of multilamellar
      vesicles (MLVs) was then investigated by differential scanning calorimetry. In
      pure IL as in water, DPPC exhibited an endothermic pretransition followed by the
      main transition. These transition temperatures and the associated enthalpies in
      ILs were higher than those in water because of a reduction of the electrostatic
      repulsion between zwitterionic head groups. To better understand the effect of
      ionic liquid on the formation of multilamellar vesicles, mixtures of BmimBF(4)
      and water, which are miscible in all proportions, were analyzed (BmimBF(4)/water
      ratio from 0% to 100%). SANS and DSC experiments demonstrated that the bilayer
      structure and stability were strongly modified by the IL content. Moreover,
      matching SANS experiments showed that BmimBF(4) molecules prefer to be located
      inside the DPPC membrane rather than in water.

PMID- 21718060
TI  - Critical behavior of the dielectric constant in asymmetric fluids.
AB  - By applying a thermodynamic theory that incorporates the concept of complete
      scaling, we derive the asymptotic temperature dependence of the critical behavior
      of the dielectric constant above the critical temperature along the critical
      isochore and below the critical temperature along the coexistence curve. The
      amplitudes of the singular terms in the temperature expansions are related to the
      changes of the critical temperature and the critical chemical potential upon the
      introduction of an electric field. The results of the thermodynamic theory are
      then compared with the critical behavior implied by the classical Clausius
      Mossotti approximation. The Clausius-Mossotti approximation fails to account for
      any singular temperature dependence of the dielectric constant above the critical
      temperature. Below the critical temperature it produces an apparent asymmetric
      critical behavior with singular terms similar to those implied by the
      thermodynamic theory, but with significantly different coefficients. We conclude
      that the Clausius-Mossotti approximation only can account for the observed
      asymptotic critical behavior of the dielectric constant when the dependence of
      the critical temperature on the electric field is negligibly small.

PMID- 21718061
TI  - String-like collective atomic motion in the melting and freezing of
      nanoparticles.
AB  - The melting of a solid represents a transition between a solid state in which
      atoms are localized about fixed average crystal lattice positions to a fluid
      state that is characterized by relative atomic disorder and particle mobility so
      that the atoms wander around the material as a whole, impelled by the random
      thermal impulses of surrounding atoms. Despite the fundamental nature and
      practical importance of this particle delocalization transition, there is still
      no fundamental theory of melting and instead one often relies on the semi
      phenomenological Lindemann-Gilvarry criterion to estimate roughly the melting
      point as an instability of the crystal lattice. Even the earliest simulations of
      melting in hexagonally packed hard discs by Alder and Wainwright indicated the
      active role of nonlocal collective atomic motions in the melting process, and
      here we utilize molecular dynamics (MD) simulation to determine whether the
      collective particle motion observed in melting has a similar geometrical form as
      those in recent studies of nanoparticle (NP) interfacial dynamics and the
      molecular dynamics of metastable glass-forming liquids. We indeed find string
      like collective atomic motion in NP melting that is remarkably similar in form to
      the collective interfacial motions in NPs at equilibrium and to the collective
      motions found in the molecular dynamics of glass-forming liquids. We also find
      that the spatial localization and extent of string-like motion in the course of
      NP melting and freezing evolves with time in distinct ways. Specifically, the
      collective atomic motion propagates from the NP surface and from within the NP in
      melting and freezing, respectively, and the average string length varies smoothly
      with time during melting. In contrast, the string-like cooperative motion peaks
      in an intermediate stage of the freezing process, reflecting a general asymmetry
      in the dynamics of NP superheating and supercooling.

PMID- 21718062
TI  - Synthesis and reactivity of cinnoline-fused cyclic enediyne.
AB  - A short and efficient synthesis of cinnoline-fused cyclic enediyne is reported.
      Richter cyclization of o-(1,3-butadiynyl)phenyltriazene produced 3-alkynyl-4
      bromocinnoline. The Sonogashira coupling of the latter with 5-hexyn-1-ol was
      employed for the introduction of a second acetylenic moiety. The crucial
      cyclization step was achieved under Nozaki-Hiyama-Kishi conditions. Cinnoline
      fused 10-membered ring enediyne is more reactive than corresponding carbocyclic
      analog and produces good yield of the Bergman cyclization product upon mild
      heating. This enediyne induces single-strand dDNA scissions upon incubation at 40
      degrees C.

PMID- 21718063
TI  - Effect of the charge state (z = -1, 0, +1) on the nuclear magnetic resonance of
      monodisperse Au25[S(CH2)2Ph]18(z) clusters.
AB  - Monodisperse Au(25)L(18)(0) (L = S(CH(2))(2)Ph) and [n-Oct(4)N(+)][Au(25)L(18)(
      )] clusters were synthesized in tetrahydrofuran. An original strategy was then
      devised to oxidize them: in the presence of bis(pentafluorobenzoyl) peroxide, the
      neutral or the negatively charged clusters react as efficient electron donors in
      a dissociative electron-transfer (ET) process, in the former case yielding
      [Au(25)L(18)(+)][C(6)F(5)CO(2)(-)]. As opposed to other reported redox methods,
      this dissociative ET approach is irreversible, easily controllable, and clean,
      particularly for NMR purposes, as no hydrogen atoms are introduced. By using this
      approach, the -1, 0, and +1 charge states of Au(25)L(18) could be fully
      characterized by (1)H and (13)C NMR spectroscopy, using one- and two-dimensional
      techniques, in various solvents, and as a function of temperature. For all charge
      states, the NMR results and analysis nicely match recent structural findings
      about the presence of two different ligand populations in the capping monolayer,
      each resonance of the two ligand families displaying distinct NMR patterns. The
      radical nature of Au(25)L(18)(0) is particularly evident in the (1)H and (13)C
      NMR patterns of the inner ligands. The NMR behavior of radical Au(25)L(18)(0) was
      also simulated by DFT calculations, and the interplay between theory and
      experiments revealed a fundamental paramagnetic contribution coming from Fermi
      contact shifts. Interestingly, the NMR patterns of Au(25)L(18)(-) and
      Au(25)L(18)(+) were found to be quite similar, pointing to the latter cluster
      form as a diamagnetic species.

PMID- 21718064
TI  - Influence of the electronic characteristics of N-donor ligands in the excited
      state of heteronuclear gold(I)-copper(I) systems.
AB  - By reaction of the heterometallic gold-silver complexes [{AuAg(C(6)F(5))(2)(N=C
      Me)}(2)](n) or [{AuAg(C(6)Cl(5))(2)(N=C-Me)}(2)](n) and CuCl in the presence of
      pyrimidine and different nitrile ligands (acetonitrile, benzonitrile, and
      cinnamonitrile), the heteronuclear complexes {[Au(C(6)X(5))(2)][Cu(L)(MU(2)
      C(4)H(4)N(2))]}(n) (X = F and L = N=C-Me (1), L = N=C-Ph (2) or N=C-CH?CH-Ph (3);
      X = Cl and L = N=C-Me (4), N=C-Ph (5), N=C-CH?CH-Ph (6)) have been prepared. The
      crystal structures of complexes {[Au(C(6)X(5))(2)][Cu(L)(MU(2)-C(4)H(4)N(2))]}(n)
      (X = F; L = N=C-CH?CH-Ph (3), X = Cl; L = N=C-Ph (5)) have been determined by X
      ray diffraction studies. The crystal structures of both complexes consists of
      polymeric chains formed by the repetition of [Au(C(6)X(5))(2)][Cu(L)(MU(2)
      C(4)H(4)N(2))] units through copper-pyrimidine bonds. Complexes 1, 2, 4, and 5
      are brightly luminescent in the solid state at room temperature and at 77 K with
      lifetimes in the microseconds range. These compounds are also luminescent in
      solution, displaying different photophysical behaviors depending on the donor
      characteristics of the solvents used. The distortion in the excited state allows
      an associative attack by donor solvents quenching one of the emitting excited
      states. DFT optimizations of the ground (S(0)) and lowest triplet excited state
      (T(1)) display the structure distortion of the complexes upon electronic
      excitation. The molecular orbitals involved in the electronic transitions
      responsible for the phosphorescence in the case of the complexes 1, 2, 4, and 5
      are related to metal (gold-copper) to ligand (pyrimidine) charge transfer
      transitions, while in the case of the nonluminescent complexes 3 and 6, the
      nonradiative electronic transition arises from metal (gold-copper) to ligand
      (cinnamonitrile) charge transfer transitions.

PMID- 21718065
TI  - Quaternary alpha,alpha-2-oxoazepane alpha-amino acids: synthesis from ornithine
      derived beta-lactams and incorporation into model dipeptides.
AB  - To explore further the chemistry of amino acid-derived beta-lactams, their
      conversion to alpha,alpha-heterocyclic quaternary amino acid derivatives is
      investigated. The latter derivatives, containing 2-oxoazepane as the alpha,alpha
      substituent, are synthesized by a simple Pd-C-catalyzed hydrogenolysis of Orn(Z)
      derived 2-azetidinones. The rearrangement from four- to seven-membered lactam
      ring is driven by the key intramolecular opening of the 1-Boc-beta-lactam,
      initiated by 7-exotrig ring closure from the NH(2) of the Orn side chain. The
      synthetic route is applied to the stereoselective preparation of enantiomerically
      pure 4-amino-3-methyl-2-oxoazepane-4-carboxylate derivatives, for which the
      structure and configuration is confirmed by X-ray diffraction. Molecular modeling
      and NMR experiments indicate that these quaternary amino acids are able to drive
      the adoption of beta-turn secondary structures when incorporated in model
      dipeptide derivatives.

PMID- 21718066
TI  - Design, synthesis, and traveling wave ion mobility mass spectrometry
      characterization of iron(II)- and ruthenium(II)-terpyridine metallomacrocycles.
AB  - New metallomacrocycles composed of 2,2':6',2"-terpyridine (tpy) ligands and
      Ru(II) or Fe(II) transition metal ions were prepared by stepwise directed
      assembly and characterized by 2D diffusion NMR spectroscopy (DOSY), electrospray
      ionization traveling wave ion mobility mass spectrometry (ESI TWIM MS), and
      molecular modeling. The supramolecular polymers synthesized include a homonuclear
      all-Ru hexamer as well as heteronuclear hexamer and nonamer with alternating
      Ru/Ru/Fe metal centers. ESI MS yields several charge states from each
      supramacromolecule. If ESI is interfaced with TWIM MS, overlapping charge states
      and the isomeric components of an individual charge state are separated based on
      their unique drift times through the TWIM region. From experimentally measured
      drift times, collision cross-sections can be deduced. The collision cross
      sections obtained for the synthesized supramacromolecules are in good agreement
      with those predicted by molecular modeling for macrocyclic structures. Similarly,
      the hydrodynamic radii of the synthesized complexes derived from 2D DOSY NMR
      experiments agree excellently with the radii calculated for macrocyclic
      architectures, confirming the ESI TWIM MS finding. ESI TWIM MS and 2D DOSY NMR
      spectroscopy provide an alternative approach for the structural analysis of
      supramolecules that are difficult or impossible to crystallize, such as the large
      macrocyclic assemblies investigated. ESI TWIM MS will be particularly valuable
      for the characterization of supramolecular assemblies not available in the
      quantity or purity required for NMR studies.

PMID- 21718067
TI  - Noncovalent interaction of dietary polyphenols with bovine hemoglobin in vitro:
      molecular structure/property-affinity relationship aspects.
AB  - The relationship between the structural properties of selected dietary
      polyphenols and their affinities for bovine hemoglobin (bHB) was investigated by
      fluorescence analysis. The presence of an additional methoxy group on flavonoids
      weakened the affinities for bHB by 1.15-13.80 times. Hydroxylation on rings A, B,
      and C also significantly affected the affinity for bHB. The glycosylation of
      flavonoids decreased the affinities for bHB by 1 order of magnitude depending on
      the conjugation site and the class of sugar moiety. Hydrogenation of the C2?C3
      double bond also decreased the binding affinity. The galloylated catechins
      exhibited higher binding affinities for bHB than nongalloylated. The
      glycosylation of resveratrol increased its affinity for bHB. The binding process
      with bHB was strongly influenced by the structural differences of dietary
      polyphenols. The affinities for bHB increased with increasing partition
      coefficients and decreased with increasing hydrogen bond donor and acceptor
      numbers of polyphenols, which suggested that the binding interaction was mainly
      caused by the hydrophobic force.

PMID- 21718068
TI  - Ultrafast cyclopolymerization for polyene synthesis: living polymerization to
      dendronized polymers.
AB  - We discovered that ultrafast cyclopolymerization of 1,6-heptadiyne derivatives
      reached completion in 1 min using a third-generation Grubbs catalyst. After
      optimization, this superior catalyst selectively produced conjugated polymers
      having a five-membered-ring structure with excellent molecular weight control and
      narrow polydispersity index (PDI). This living polymerization allowed us to
      prepare fully conjugated diblock copolymers with narrow PDIs. Lastly, this
      catalyst was active enough to polymerize macromonomers with G-3 dendrons in a
      living manner as well. This dendronized polymer with a highly regioregular
      polymer backbone and bulky dendrons was visualized by atomic force microscopy,
      which revealed the structure of a single molecular wire surrounded by insulating
      dendrons.

PMID- 21718069
TI  - Phosphorus-based functional groups as hydrogen bonding templates for rotaxane
      formation.
AB  - We report on the use of the hydrogen bond acceptor properties of some phosphorus
      containing functional groups for the assembly of a series of [2]rotaxanes.
      Phosphinamides, and the homologous thio- and selenophosphinamides, act as
      hydrogen bond acceptors that, in conjunction with an appropriately positioned
      amide group on the thread, direct the assembly of amide-based macrocycles around
      the axle to form rotaxanes in up to 60% yields. Employing solely phosphorus-based
      functional groups as the hydrogen bond accepting groups on the thread, a
      bis(phosphinamide) template and a phosphine oxide-phosphinamide template afforded
      the corresponding rotaxanes in 18 and 15% yields, respectively. X-ray
      crystallography of the rotaxanes shows the presence of up to four intercomponent
      hydrogen bonds between the amide groups of the macrocycle and various hydrogen
      bond accepting groups on the thread, including rare examples of amide-to
      phosphinamide, -thiophosphinamide, and -selenophosphinamide groups. With a
      phosphine oxide-phosphinamide thread, the solid-state structure of the rotaxane
      is remarkable, featuring no direct intercomponent hydrogen bonds but rather a
      hydrogen bond network involving water molecules that bridge the H-bonding groups
      of the macrocycle and thread through bifurcated hydrogen bonds. The incorporation
      of phosphorus-based functional groups into rotaxanes may prove useful for the
      development of molecular shuttles in which the macrocycle can be used to hinder
      or expose binding ligating sites for metal-based catalysts.

PMID- 21718070
TI  - Gating the mechanistic pathway to the elusive 4-membered ring azeteoporphyrin.
AB  - Photolysis of metalated (Cu and Ni) and free base 2-diazo-3-oxochlorins within a
      frozen matrix (lambda = 457.9 nm, toluene, 80 K) generates a single
      photointermediate with a hypsochromically shifted electronic absorption spectrum
      relative to the starting diazochlorins. The appearance of ketene (~2131 cm(-1))
      and azete (~1670 cm(-1)) vibrations in infrared absorption and Raman spectra,
      respectively, identifies this intermediate as resulting from the Wolff
      rearrangement of the diazochlorins upon N(2) loss. Computational modeling of the
      vibrational spectra and TDDFT simulation of the electronic transitions of
      potential photointermediates corroborate this assignment. Isolation and analysis
      of photoproducts of these diazochlorins formed within n-butanol-doped frozen
      toluene matrices indicate near exclusive formation of azeteoporphyrins. In sharp
      contrast, room temperature laser photolysis of these materials yields a mixture
      of photoproducts deriving from the presence of both carbene and ketene
      intermediates. Computational modeling of the intramolecular reactivity of the
      proposed sp(2) carbene intermediate shows exclusive bond insertion to the
      adjacent phenyl group, and no evidence of Wolff rearrangement. Computational
      reaction profile analyses reveal that the barrierless Wolff rearrangement
      proceeds via an out-of-plane carbene electronic configuration that is generated
      directly during the loss of N(2). The formation of out-of-plane carbene,
      resulting in the exclusive formation of the observed ketene photointermediate at
      low temperatures, is consistent with orbital symmetry considerations and by the
      geometric constraints imposed by the frozen matrix. Combined, this leads to a
      model showing that azeteoporphyrin formation via the Wolff rearrangement is
      dependent upon the structural disposition of the adjacent framework, and the
      specific reaction intermediate formed is very sensitive to this feature.

PMID- 21718071
TI  - Structural insights into the pre-amyloid tetramer of beta-2-microglobulin from
      covalent labeling and mass spectrometry.
AB  - The main pathogenic process underlying dialysis-related amyloidosis is the
      accumulation of beta-2-microglobulin (beta2m) as amyloid fibrils in the
      musculoskeletal system, and some evidence suggests that Cu(II) may play a role in
      beta2m amyloid formation. Cu(II)-induced beta2m fibril formation is preceded by
      the formation of discrete, oligomeric intermediates, including dimers, tetramers,
      and hexamers. In this work, we use selective covalent labeling reactions combined
      with mass spectrometry to investigate the amino acids responsible for mediating
      tetramer formation in wild-type beta2m. By comparing the labeling patterns of the
      monomer, dimer, and tetramer, we find evidence that the tetramer interface is
      formed by the interaction of D strands from one dimer unit and G strands from
      another dimer unit. These covalent labeling data along with molecular dynamics
      calculations allow the construction of a tetramer model that indicates how the
      protein might proceed to form even higher-order oligomers.

PMID- 21718072
TI  - Ratiometric detection of mitochondrial thiols with a two-photon fluorescent
      probe.
AB  - We report a ratiometric two-photon probe (SSH-Mito) for mitochondrial thiols.
      This probe shows a marked blue-to-yellow emission color change in response to
      RSH, a significant two-photon cross section, good mitochondrial thiol
      selectivity, low cytotoxicity, and insensitivity to pH over the biologically
      relevant pH range, allowing the direct visualization of RSH levels in live cells
      as well as in living tissues at 90-190 MUm depth without interference from other
      biologically relevant species through the use of two-photon microscopy.

PMID- 21718073
TI  - DNA exposure to buckminsterfullerene (C60): toward DNA stability, reactivity, and
      replication.
AB  - Buckminsterfullerene (C(60)) has received great research interest due to its
      extraordinary properties and increasing applications in manufacturing industry
      and biomedical technology. We recently reported C(60) could enter bacterial cells
      and bind to DNA molecules. This study was to further determine how the DNA-C(60)
      binding affected the thermal stability and enzymatic digestion of DNA molecules,
      and DNA mutations. Nano-C(60) aggregates and water-soluble fullerenols were
      synthesized and their impact on DNA biochemical and microbial activity was
      investigated. Our results revealed that water-soluble fullerenols could bind to
      lambda DNA and improve DNA stability remarkably against thermal degradation at 70
      85  degrees C in a dose-dependent manner. DNase I and HindIII restriction
      endonuclease activities were inhibited after interacting with fullerenols at a
      high dose. Experimental results also showed the different influence of fullerenol
      and nano-C(60) on their antibacterial mechanisms, where fullerenols contributed
      considerable impact on cell damage and mutation rate. This preliminary study
      indicated that the application of fullerenols results in significant changes in
      the physical structures and biochemical functions of DNA molecules.

PMID- 21718074
TI  - Liquid chromatography/mass spectrometry method for determination of
      perfluorooctane sulfonyl fluoride upon derivatization with benzylamine.
AB  - Perfluorooctane sulfonyl fluoride (PFOSF) is a main precursor of environmentally
      ubiquitous perfluorooctanesulfonate (PFOS), and the quantity released to the
      environment is substantial. Determination of PFOSF, particularly at low
      concentrations, presents significant challenges for high-performance liquid
      chromatography and liquid chromatography/mass spectrometry (LC/MS) analyses due
      to the lack of chromophore and ionizable functional group, respectively. In this
      study, a new method was developed by derivatizing PFOSF with benzylamine to allow
      rapid quantitative analysis by using LC/MS. The method demonstrated good
      linearity in the range from 2 to 80 ng mL(-1) with r(2) > 0.994 for the
      derivatization product while the absolute detection limit was 2.5 pg. Liquid
      liquid and liquid-solid extraction procedures were established for analysis of
      water and soil samples, and recoveries were in the range of 51-128%. In addition,
      the derivatization was selective for PFOSF, whereas PFOS did not nearly react.
      The developed simple analytical method with good reproducibility might not only
      be applied for analysis of PFOSF in the environment but also be applicable for
      supporting investigations on environmental fate of PFOSF, particularly its
      environmental and biotransformation to PFOS.

PMID- 21718075
TI  - Microwave spectrum and conformational composition of 2-fluoroethylisocyanide.
AB  - The microwave spectrum of 2-fluoroethylisocyanide, FCH(2)CH(2)N=C, has been
      investigated in the whole 50-120 GHz spectral region. Selected portions of the
      spectrum in the range of 18-50 GHz have also been recorded. The microwave spectra
      of the ground state and vibrationally excited states of two conformers have been
      assigned. Accurate spectroscopic constants have been derived from a large number
      of microwave transitions. The F-C-C-N chain of atoms is antiperiplanar in one of
      these rotamers and synclinal in the second conformer. The energy difference
      between the two forms was obtained from relative intensity measurements. It was
      found that the synclinal conformer is favored over the antiperiplanar form by
      0.7(5) kJ/mol. Quantum chemical calculations at the high CCSD/cc-pVTZ and
      B3LYP/cc-pVTZ levels of theory were performed. Most, but not all, of the
      spectroscopic constants predicted in these calculations are in good agreement
      with the experimental counterparts. The theoretical calculations correctly
      indicate that the F-C-C-N dihedral angle in the synclinal form is about 67
      degrees  but underestimate the magnitude of the gauche effect and erroneously
      predict the antiperiplanar rotamer to be 1.3-1.6 kJ/mol more stable than the
      synclinal conformer.

PMID- 21718076
TI  - One-electron reduction of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin:
      a pulse radiolysis study.
AB  - Geldanamycin, a benzoquinone ansamycin antibiotic, is a natural product inhibitor
      of Hsp90 with potent and broad anticancer properties but with unacceptable levels
      of hepatotoxicity. Consequently, numerous structural analogs, which differ only
      in their 17-substituent, have been synthesized including the water-soluble and
      less toxic 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG,
      Alvespimycin). It has been suggested that the different hepatotoxicity reflects
      the redox active properties of the quinone moiety. The present pulse radiolysis
      study was aimed at studying the one-electron reduction of 17-DMAG. The UV-visible
      spectrum of the semiquinone radical, its pK(a), and the second-order rate
      constants for the reactions of 17-DMAG with CO(2)(*-) and (CH(3))(2)C(*)OH have
      been obtained. The reduction potential of 17-DMAG has been determined to be -194
      +/- 6 mV (vs NHE) using oxygen, 1,4-naphthoquinone, and menadione as electron
      acceptors. This reduction potential is lower than that of O(2) demonstrating that
      thermodynamically the semiquinone radical can reduce O(2) to superoxide,
      particularly since the concentration of O(2) is expected to exceed that of the
      drug in cells and tissues.

PMID- 21718077
TI  - Facile fabrication of colored superhydrophobic coatings by spraying a pigment
      nanoparticle suspension.
AB  - Superhydrophobic coatings were prepared by spraying a pigment nanoparticle
      suspension. By changing the type of pigment nanoparticles, the colors of the
      coating could be controlled. The particle size of the pigments, which determines
      the surface structure of the coatings, played an important role in exhibiting
      superhydrophobicity. The spray-coating process is applicable to a variety of
      materials (e.g., copper, glass, paper, coiled wire, and tied thread), and the
      superhydrophobicity was repairable.

PMID- 21718078
TI  - Process-based reactive transport model to quantify arsenic mobility during
      aquifer storage and recovery of potable water.
AB  - Aquifer storage and recovery (ASR) is an aquifer recharge technique in which
      water is injected in an aquifer during periods of surplus and withdrawn from the
      same well during periods of deficit. It is a critical component of the long-term
      water supply plan in various regions, including Florida, USA. Here, the viability
      of ASR as a safe and cost-effective water resource is currently being tested at a
      number of sites due to elevated arsenic concentrations detected during
      groundwater recovery. In this study, we developed a process-based reactive
      transport model of the coupled physical and geochemical mechanisms controlling
      the fate of arsenic during ASR. We analyzed multicycle hydrochemical data from a
      well-documented affected southwest Floridan site and evaluated a
      conceptual/numerical model in which (i) arsenic is initially released during
      pyrite oxidation triggered by the injection of oxygenated water (ii) then largely
      complexes to neo-formed hydrous ferric oxides before (iii) being remobilized
      during recovery as a result of both dissolution of hydrous ferric oxides and
      displacement from sorption sites by competing anions.

PMID- 21718079
TI  - Psychological distress and trends in healthcare expenditures and outpatient
      healthcare.
AB  - OBJECTIVES: To determine whether trends in psychological distress exist in the
      United States and whether trends in healthcare expenditures and outpatient visits
      were associated with psychological distress. STUDY DESIGN: Sequential cross
      sectional study of nationally representative data. METHODS: We examined data from
      the National Health Interview Survey (NHIS) from 1997 to 2004 linked to 2 years
      of subsequent Medical Expenditure Panel Survey (MEPS) data. Psychological
      distress was measured in the NHIS using the K6, a 6-item scale of the Kessler
      Psychological Distress Scale, which we classified as no/low, mild-moderate, or
      severe. We examined subsequent annualized total, outpatient, and office-based
      expenditures, and outpatient and office-based visits from MEPS. RESULTS:
      Psychological distress remained stable from 1997 to 2004. There were upward
      trends in overall healthcare expenditures (P <.001) and outpatient expenditures
      (P <.001), but not outpatient visits. Overall healthcare expenditures, outpatient
      expenditures, and outpatient visits significantly increased as psychological
      distress increased from no/low to mild-moderate to severe. The interaction
      between psychological distress strata and year was not significant for
      expenditures or for visits. CONCLUSIONS: The upward trend in total and outpatient
      healthcare expenditures in the United States appears unrelated to psychological
      distress, although healthcare expenditures are consistently higher among those
      with greater psychological distress. Future work will explore the impact of
      treatment on costs and stability of the nation's mental health over time.

PMID- 21718080
TI  - Post-treatment surveillance in a large cohort of patients with colon cancer.
AB  - OBJECTIVES: To determine how patients complied with different components of
      guideline-recommended post-treatment surveillance in a large nationwide
      population-based cohort of patients with colon cancer. STUDY DESIGN:
      Retrospective cohort study. METHODS: We used the linked Surveillance,
      Epidemiology, and End Results-Medicare database to identify patients 66 years or
      older diagnosed as having stage I to stage III colon adenocarcinoma between
      January 2000 and June 2002 with a follow-up duration of at least 3.5 years. After
      tumor resection, patients who completed at least 2 office visits per year for 3
      years, at least 2 carcinoembryonic antigen tests per year (in the first and
      second years of follow-up), and at least 1 colonoscopy within 3 years were
      defined as meeting the recommended post-treatment care. RESULTS: We identified
      7348 patients, with a median follow-up duration of 59 months. Adherence to post
      treatment surveillance was 83.9% for office visits, 29.4% for carcinoembryonic
      antigen tests, and 74.3% for colonoscopy. Younger age at diagnosis, white
      race/ethnicity, married status, advanced tumor stage, fewer comorbidities, and
      chemotherapy use were significantly associated with guideline adherence.
      CONCLUSIONS: Adherence to colon cancer posttreatment surveillance was low,
      although proportions of patients complying with office visits and colonoscopy
      were reasonably high. Underlying reasons for noncompliance, which varied by type
      of service, may need further investigation.

PMID- 21718081
TI  - Adherence to laboratory test requests by patients with diabetes: the Diabetes
      Study of Northern California (DISTANCE).
AB  - OBJECTIVES: To estimate rates and predictors of clinical laboratory test
      completion by patients with diabetes after provider referral. STUDY DESIGN:
      Prospective cohort study. METHODS: Among 186,306 adult members with diabetes in
      Kaiser Permanente Northern California, we searched the electronic medical records
      (July 1, 2008, to June 30, 2009) of each patient for the first outpatient order
      to obtain the following laboratory tests commonly used to measure risk factor
      control or adverse effects of pharmacotherapy: levels of glycosylated hemoglobin,
      low density lipoprotein cholesterol, serum creatinine, urinary albumin, or
      creatine kinase (the latter only among persons using statins). We measured
      laboratory test attendance as completion of an order (including time to results)
      within 6 months of the referral date and looked for variations by subgroups.
      RESULTS: Laboratory test attendance ranged from 86% for glycosylated hemoglobin
      level to 73% for serum creatinine level. Time to laboratory test attendance was a
      median of 7 to 11 days and a mean of 25 to 30 days. Laboratory test attendance
      was more likely for women and older patients or for orders after a face-to-face
      provider visit and was less likely for orders by a pharmacist. However, most
      variations (even by laboratory copayment) were small or not clinically
      substantive. In subanalyses, we observed no clinically significant variations by
      race/ethnicity, socioeconomic status, trust in provider, or patient-provider
      communication and found no association with depressive symptoms, health literacy,
      or English fluency. CONCLUSION: The fact that 1 in 7 patients did not complete
      laboratory tests within 6 months of the provider referral may help explain why
      healthcare services seem to fall short of optimal diabetes care.

PMID- 21718082
TI  - Identification of patients likely to benefit from care management programs.
AB  - OBJECTIVES: To compare predictive modeling (PM), selection by primary care
      physician (PCP), and a combination of both as approaches to prospective patient
      identification for care management programs. STUDY DESIGN: Observational study.
      METHODS: A total of 6026 beneficiaries of a statutory health insurance program in
      Germany served as a sample for patient identification by PM and selection by PCP.
      The resulting mutually exclusive subpopulations were compared for care needs (eg,
      morbidity burden), healthcare utilization (previous all-cause hospitalizations
      and predicted costs), and prior participation in intensified care programs (as a
      proxy for amenability). Data sources were insurance claims data and a patient
      survey. RESULTS: Patients were selected for eligibility in a care management
      program by PM (n = 301), selection by PCP (n = 203), or a combination of both (n
      = 32). Compared with 5490 nonselected patients, all eligible patients had
      significantly higher morbidity burden and more previous hospitalizations.
      Compared with selection by PCP, PM identified patients at significantly higher
      risk for future healthcare utilization, with predicted annual healthcare costs of
      8760 euro (95% confidence interval [CI], 8314-9205 euro) vs 4541 euro (95% CI,
      4094-4989 euro) (P <.01). Compared with patients selected by PM, patients
      selected by PCP had significantly higher rates of prior participation in
      intensified care programs (80.8% vs 56.4%, P <.01). Patients selected
      independently by both approaches seemed to be at high risk for future healthcare
      utilization, with predicted annual healthcare costs of 8279 euro (95% CI, 7465
      9092 euro), and 84.6% had prior participation in intensified care programs.
      CONCLUSIONS: Identification of high-risk patients most likely to benefit from and
      participate in care management programs may be facilitated by a combination of PM
      and selection by PCP.

PMID- 21718083
TI  - Promoting electronic health record adoption among small independent primary care
      practices.
AB  - OBJECTIVES: To describe the benefits and limitations of incentive arrangements
      used to engage small primary care practices to adopt electronic health records
      (EHRs). STUDY DESIGN: Retrospective review of program outreach efforts and EHR
      enrollment rates. METHODS: Comparison of benefits and limitations of various
      promotional strategies in addition to a city subsidy. Measures of enrollment
      progress include the mean number of outreach attempts, the mean number of days
      from first attempt to enrollment, and the enrollment yield. Selected practice
      demographics were collected for comparison purposes. RESULTS: Of 890 providers
      representing 217 practices who were eligible for the city subsidy, 37.7%
      enrolled, with a mean of 96.6 days from first attempt to enrollment and a mean of
      10 outreach attempts. The offer for full payment of technical assistance fees and
      hardware yielded an additional 100 providers representing 43 practices, a 14.1%
      enrollment rate. This group also had the highest mean number of days from first
      attempt to enrollment (236.0 days) and the highest mean number of outreach
      attempts (22 attempts). The offer for a partial rebate had the lowest yield (a
      6.2% enrollment rate), a mean of 169.3 days from first attempt to enrollment, and
      a mean number of 19 outreach attempts. CONCLUSIONS: Because of diverse needs and
      levels of awareness in the EHR adoption process, a flexible milestone-based
      process is needed to engage primary care providers. In particular, community
      influence and additional funding were necessary for increasing enrollment among
      providers in medically underserved neighborhoods. These providers also required
      persistent and numerous follow-up attempts. Because billions of dollars in
      federal aid are being offered, effective local recruitment strategies are needed
      to facilitate provider engagement to increase EHR adoption rates.

PMID- 21718084
TI  - Clinicopathological features of colorectal cancer in patients over 70 years of
      age.
AB  - OBJECTIVE: The aim was to identify the clinical factors and tumor characteristics
      that predict mortality and survival in patients older than 70 years with
      colorectal adenocarcinoma. MATERIAL AND METHODS: One hundred and ninety-four
      patients with colorectal cancer aged over 70 years were identified from a
      computer database and their clinical variables were analyzed by both univariate
      and multivariate analyses. RESULTS: All patients underwent resective surgery, 79%
      radical and 21% palliative resection, and postoperative mortality was 6% being
      associated with the presence of postoperative complications, especially
      anastomotic leakage. The cumulative 5-year survival was 38%, the median survival
      35 months, and the cancer-specific 5-year survival 48% and this did not differ
      significantly between the age groups. The recurrence rate after radical surgery
      was 30%, being 12, 22, 56, and 100% in Dukes classes A, B, C, and D. Kaplan-Meier
      estimates indicated that gender, Dukes staging, grade of tumor, number of lymph
      node metastasis, venous invasion, and recurrent disease were significant
      predictors of survival, but in the Cox regression model, only venous invasion and
      recurrent disease were independent prognostic factors of survival. CONCLUSIONS:
      Low mortality and acceptable survival can be achieved in elderly patients with
      colorectal cancer. Venous invasion and recurrent cancer are independent
      predictors of survival.

PMID- 21718085
TI  - What is the optimal treatment for pancreatic pseudocysts?

PMID- 21718086
TI  - Use of threshold and mode of action in risk assessment.
AB  - Under current guidelines, exposure guidelines for toxicants are determined by
      following one of two different tracks depending on whether the toxicant's mode of
      action (MOA) is believed to involve an exposure threshold. Although not denying
      the existence of thresholds, this paper points out problems with how the
      threshold concept and MOA is used in risk assessment. Thresholds are frequently
      described using imprecise terms that imply some unspecified increase in risk,
      which robs them of any meaning (any reasonable dose response will satisfy such a
      definition) and tacitly implies a value judgment about how large a risk is
      acceptable. MOA is generally used only to inform a threshold's existence and not
      its value. Often MOA is used only to conclude that the adverse effect requires an
      upstream cellular or biochemical response for which a threshold is simply
      assumed. Data to inform MOA often come from animals, which complicates evaluation
      of the role of human variation in genetic and environmental conditions, and the
      possible interaction of the toxicant with processes already producing background
      toxicity in humans. In response to these and other problems with the current two
      track approach, this paper proposes a modified point of departure/safety factor
      approach to setting exposure guidelines for all toxicants. MOA and the severity
      of the toxic effect would be addressed using safety factors calculated from
      guidelines established by consensus and based on scientific judgment. The method
      normally would not involve quantifying low-dose risk, and would not require a
      threshold determination, although MOA information regarding the likelihood of a
      threshold could be used in setting safety factors.

PMID- 21718087
TI  - Maternal allergy acts synergistically with cigarette smoke exposure during
      pregnancy to induce hepatic fibrosis in adult male offspring.
AB  - Maternal environmental exposures during pregnancy are known to affect disease
      onset in adult offspring. For example, maternal asthma exacerbations during
      pregnancy can worsen adult asthma in the offspring. Cigarette smoking during
      pregnancy is associated with future onset of cardiovascular disease, obesity and
      diabetes. However, little is known about the effect of maternal environmental
      exposures on offspring susceptibility to liver disease. This pilot study examined
      the long-term effect of maternal allergen challenge and/or cigarette smoking
      during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring.
      Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1
      dams were exposed to mainstream cigarette smoke (MCS) or filtered air from
      gestational day 4 until parturition. Eight weeks postnatally, offspring were
      sacrificed for comparison of hepatic histology and mRNA expression. Adult male
      offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed
      significantly increased liver fibrosis (9.2% collagen content vs. <4% for all
      other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA
      levels. From the results here, we concluded that maternal allergen challenge in
      combination with cigarette smoke exposure during pregnancy may be an important
      risk factor for liver disease in adult male offspring.

PMID- 21718088
TI  - The pharmacokinetics of recombinant human interferon-alpha-2b poly(lactic-co
      glycolic acid) microspheres in rats.
AB  - Interferon-alpha2b (IFN alpha-2b) microspheres were prepared at various
      concentrations (5%, 10%, 15%, 20% and 25%) and viscosities (0.39, 0.6, 0.89 and
      1.13 dL/g) of poly(lactic-co-glycolic acid) (PLGA) using double emulsion solvent
      evaporation. The optimal formulation of IFN alpha-2b microspheres was determined
      to be 0.89 dL/g PLGA, as assessed by the in vitro release test. The
      pharmacokinetics of IFN alpha-2b microspheres was investigated. Nine groups of
      rats were injected intramuscularly with three doses (0.5, 1 and 2 MIU) of
      commercial lyophilized IFNalpha-2b injection or IFN alpha-2b microspheres. At a
      dose of 0.5 MIU, the IFN alpha-2b microsphere released significantly longer than
      that of the IFN alpha-2b injection. At a dose of 2 MIU, each pharmacokinetics
      parameter of microspheres prepared with the IFNa-2b stock solution was manifestly
      greater than those of the injection. Our study indicated that the IFN alpha-2b
      microspheres prepared in 15% of 0.89 dL/g PLGA provided a sustained drug effect
      for up to 21 days in rats.

PMID- 21718089
TI  - Prevalence of the metabolic syndrome and its relationship with diabetes mellitus
      by aging.
AB  - INTRODUCTION: It is important to make a prompt diagnosis of metabolic syndrome
      (MetS) in order to prevent the development of cardio-/cerebro- vascular diseases
      and diabetes mellitus (DM). The authors estimated the risk of development of DM
      by the presence/absence of MetS and age groups. METHODS: A cross-sectional study
      of subjects undergoing intensive health examination was conducted (3149 men aged
      30-69 years). Diagnosis of MetS was based on the criteria of the National
      Cholesterol Education Program Expert Panel (NCEP). RESULTS: The prevalence of DM
      occurring in association with MetS increased with age; it was 11.9% in subjects
      with MetS in their 30s, it was 19.8% in subjects with MetS in their 60s. The
      prevalence of DM among subjects who had one or two components of MetS also
      increased with age. There was a significant progressive increase of the odds
      ratio in subjects in their 30s, 40s, 50s and 60s who were judged as having MetS;
      significant increase of the odds ratio was seen in subjects in their 60s, even in
      those who were not judged as having MetS. CONCLUSIONS: Subjects with MetS show a
      high prevalence of DM, and the prevalence increased with age in the subjects.

PMID- 21718090
TI  - Spacebridge to armenia: a look back at its impact on telemedicine in disaster
      response.
AB  - On December 7, 1988, an earthquake destroyed a significant portion of the Spitak
      Region of Soviet Armenia. The destruction resulted in significant death toll,
      building and infrastructure destroyed, and the displacement of hundreds of
      thousands of people. The entire local medical infrastructure was significantly
      damaged. Before the disaster, the space medical leadership of the United States
      and the Union of Soviet Socialist Republics were collaborating on joint
      activities in medicine and biology. The leaders of this collaborative effort
      devised an approach to support a disaster recovery utilizing telecommunications
      assets. This effort was focused on healthcare in a postdisaster event and became
      known as the Spacebridge to Armenia. This spacebridge was put in place 5 months
      after the calamity and operated for several months in the spring-summer of 1989.
      The spacebridge was extended to Ufa, Russia, in response to a second disaster.
      The influence of the Spacebridge to Armenia in the 20 years since has been
      significant. This article summarizes how telemedicine has evolved from the
      response to the earthquake in 1988. It presents lessons learned and illustrates
      the many influences that have been made.

PMID- 21718091
TI  - Attitudes and awareness of web-based self-care resources in the military: a
      preliminary survey study.
AB  - Web-based self-care resources have a number of potential benefits for military
      service members (SMs) and their families such as convenience, anonymity, and
      immediate 24/7 access to useful information. There is limited data available,
      however, regarding SM and military healthcare provider use of online self-care
      resources. Our goal with this study was to conduct a preliminary survey
      assessment of self-care Web site awareness, general attitudes about use, and
      usage behaviors of Web-based self-care resources among SMs and military
      healthcare providers. Results show that the majority of SMs and providers use the
      Internet often, use Internet self-care resources, and are willing to use
      additional Web-based resources and capabilities. SMs and providers also indicated
      a preference for Web-based self-care resources as adjunct tools to face-to
      face/in-person care. Data from this preliminary study are useful for informing
      additional research and best practices for integrating Web-based self-care for
      the military community.

PMID- 21718092
TI  - A systematic review of e-health interventions for physical activity: an analysis
      of study design, intervention characteristics, and outcomes.
AB  - OBJECTIVE: This systematic literature review of e-health interventions targeting
      physical activity (PA) from January 2006 to November 2010 provides an updated and
      critical picture of the state of e-health as a facilitator for PA interventions.
      MATERIALS AND METHODS: A systematic search yielded 31 articles that fit into the
      inclusion/exclusion criteria, which were analyzed in terms of study design
      quality, intervention characteristics, and support for e-health in PA
      interventions. RESULTS: The included articles met most of the study design
      criteria, but many did not isolate e-health technologies or use power analyses to
      calculate sample sizes. The interventions reflected a variety of technologies,
      audiences, and methods, and showed consistent use of theoretical frameworks to
      guide the interventions. Results regarding support for e-health's effectiveness
      in PA interventions were mixed and cannot provide definite conclusions. Only
      seven studies used pure control groups, and of those, four demonstrated support
      for e-health but the others showed no significant differences. The majority of
      studies using comparison groups showed no significant differences between
      conditions. No notable patterns emerged among the studies that did show support
      for e-health. CONCLUSIONS: Future research should utilize more rigorous methods
      that allow for better comparison across studies, such as power analyses, pure
      control groups, and objective PA measurements, which could lead to more
      definitive results regarding e-health's effectiveness for PA interventions.

PMID- 21718093
TI  - E-healthcare maturity in Taiwan.
AB  - The purpose of this study was to explore the status of e-healthcare maturity in
      Taiwan following a nationwide investigation sponsored by the Department of
      Health. Based on Nolan's stage model and related studies, we propose a
      multidimensional model to gain a better understanding of the current status of e
      healthcare maturity in hospitals. The target subjects included every hospital in
      Taiwan. A total of 538 hospitals were successfully interviewed, showing a high
      response rate of 94.4%. The results indicate that the overall e-healthcare
      maturity of Taiwanese hospitals is fairly high. Such a high degree of maturity is
      critical for formulating e-healthcare policy to stimulate the exchange of
      electronic medical record. This article provides a brief comparison of the
      situation in other countries and posits that Taiwan holds a position of relative
      maturity in the world of e-healthcare development.

PMID- 21718094
TI  - Insulin pump therapy started at the time of diagnosis: effects on glycemic
      control and pancreatic beta-cell function in type 1 diabetes.
AB  - BACKGROUND: In the interest of preserving residual insulin secretory capacity
      present at the time of diagnosis with type 1 diabetes (T1D), we compared the
      efficacy of starting insulin pump therapy at diagnosis with standard multiple
      daily insulin injections (MDIs). METHODS: We conducted a prospective, randomized,
      pilot trial comparing MDI therapy with continuous subcutaneous insulin therapy
      (pump therapy) in 24 patients, 8-18 years old, with newly diagnosed T1D. Subjects
      were evaluated at enrollment and 1, 3, 6, 9, and 12 months after initial
      diagnosis of T1D. Preservation of insulin secretion, measured by mixed-meal
      stimulated C-peptide secretion, was compared after 6 and 12 months of treatment.
      Between-group differences in glycosylated hemoglobin (HbA1c), continuous glucose
      sensor data, insulin utilization, anthropometric measures, and patient
      satisfaction with therapy were also compared at multiple time points. RESULTS:
      Initiation of pump therapy within 1 month of diagnosis resulted in consistently
      higher mixed-meal tolerance test-stimulated C-peptide values at all time points,
      although these differences were not statistically significant. Nonetheless,
      improved glycemic control was observed in insulin pump-treated subjects (more
      time spent with normoglycemia, better mean HbA1c), and pump-treated subjects
      reported comparatively greater satisfaction with route of treatment
      administration. CONCLUSIONS: Initiation of insulin pump therapy at diagnosis
      improved glycemic control, was well tolerated, and contributed to improved
      patient satisfaction with treatment. This study also suggests that earlier use of
      pump therapy might help to preserve residual beta-cell function, although a
      larger clinical trial would be required to confirm this.

PMID- 21718095
TI  - Inhibition of fibroblast differentiation of muscle-derived stem cells in cell
      implantation treatment of stress urinary incontinence.
AB  - The aim of this study was to investigate the effects of transforming growth
      factor-beta1 (TGF-beta1) stimulation and the blocking of the TGF-beta1/Smad3
      signaling pathway by vector-mediated Smad3 shRNA on muscle-derived stem cells
      (MDSCs) in cell implantation treatment of stress urinary incontinence (SUI) of
      the rat. MDSCs were infected with the GC-shSmad3 lentivirus vector. Five days
      after infection, the cells were treated with TGF-beta1. The expression levels of
      desmin (a marker of muscle differentiation) and vimentin (a marker of fibroblast
      differentiation) were tested by real-time PCR and Western blot. GC-shSmad3
      lentivirus-infected MDSCs were injected into the bladder neck and proximal
      urethra of SUI rats. Urodynamic test was used to measure leak point pressure
      (LPP) at 2 weeks and 4 weeks after MDSC transplantation. Upregulated expression
      of vimentin and downregulated expression of desmin were found in MDSCs after
      culture with TGF-beta1 in vitro. GC-shSmad3 lentivirus infection inhibited
      fibroblast differentiation of MDSCs but allowed muscle differentiation with
      desmin expression. In vivo experiments showed that GC-shSmad3 lentivirus
      infection could improve MDSC-mediated repairing of urethra sphincter function. In
      conclusion, blocking Smad3 expression inhibits the fibroblast differentiation of
      MDSCs induced by TGF-beta1 in vitro and improves the repairing of urethral
      sphincter function by inhibiting the fibroblast differentiation of MDSCs in a rat
      model of SUI in vivo.

PMID- 21718096
TI  - Multifactorial treatment for improvement of renal function and cardiovascular
      risk: an ATTEMPT for patients with metabolic syndrome and chronic kidney disease.

PMID- 21718097
TI  - Telmisartan for the management of patients at high cardiovascular risk.
AB  - BACKGROUND: Cardiovascular disease (CVD) places a significant burden on
      healthcare providers. High blood pressure (BP) is the single most prevalent risk
      factor for CVD worldwide and is responsible for more deaths than any other risk
      factor. 'Cardiovascular (CV) high-risk patients' make up the broad cross-section
      of patients in the middle of the risk spectrum for CVD progression that is
      referred to as the CV continuum and includes those with atherothrombotic disease,
      those with target organ damage associated with type 2 diabetes and those with
      multiple risk factors. Angiotensin II is involved in CVD progression at every
      stage of the CV continuum, making the renin-angiotensin system a rational target
      for pharmacologic intervention. Angiotensin II receptor blockers (ARBs) offer a
      better tolerated alternative to angiotensin converting enzyme inhibitors, with
      greater long-term adherence. The ARB telmisartan recently received an indication
      for CV prevention. SCOPE: A PubMed literature search was conducted to identify
      evidence on the use of telmisartan for preventing CV events. FINDINGS:
      Telmisartan has a favourable safety and tolerability profile, and has
      demonstrated efficacious and long-lasting 24-hour BP reductions, whether as
      monotherapy or in combination with hydrochlorothiazide or amlodipine. In the
      largest CV prevention trial program undertaken with an ARB (the ONgoing
      Telmisartan Alone and in combination with Ramipril Global Endpoint Trial;
      ONTARGET), telmisartan 80 mg/day alone was as effective as ramipril in reducing
      the composite primary endpoint of CV mortality, non-fatal myocardial infarction,
      non-fatal stroke and hospitalization for heart failure in CV high-risk patients.
      However, patients were significantly more likely to adhere to treatment with
      telmisartan than ramipril due to its better tolerability. CONCLUSION: To date,
      telmisartan is the only ARB indicated to reduce CV morbidity in a broad CV high
      risk population.

PMID- 21718098
TI  - Bridging the digital divide in diabetes: family support and implications for
      health literacy.
AB  - Abstract   Background: Patient web portals (PWPs) offer patients remote access to
      their medical record and communication with providers. Adults with health
      literacy limitations are less likely to access and use health information
      technology (HIT), including PWPs. In diabetes, PWP use has been associated with
      patient satisfaction, patient-provider communication, and glycemic control.
      METHODS: Using mixed methods, we explored the relationships between health
      literacy, numeracy, and computer literacy and the usage of a PWP and HIT.
      Participants (N=61 adults with type 2 diabetes) attended focus groups and
      completed surveys, including measures of health literacy, numeracy, and computer
      anxiety (an indicator of computer literacy) and frequency of PWP and HIT use.
      RESULTS: Computer literacy was positively associated with health literacy
      (r=0.41, P<0.001) and numeracy (r=0.35, P<0.001), but health literacy was not
      associated with numeracy. Participants with limited health literacy (23%),
      numeracy (43%), or computer literacy (25%) were no less likely to access PWPs or
      HIT, but lower health literacy was associated with less frequent use of a
      computer to research diabetes medications or treatments. In focus groups,
      participants spontaneously commented on family support when accessing and using
      PWPs or HIT for diabetes management. CONCLUSIONS: Participants reported family
      members facilitated access and usage of HIT, taught them usage skills, and acted
      as online delegates. Participant statements suggest family members may bridge the
      HIT "digital divide" in diabetes by helping adults access a PWP or HIT for
      diabetes management.

PMID- 21718099
TI  - Feline bone marrow-derived mesenchymal stem cells express several pluripotent and
      neural markers and easily turn into neural-like cells by manipulation with
      chromatin modifying agents and neural inducing factors.
AB  - Recent studies suggest that cellular therapies that utilize mesenchymal stem
      cells (MSCs), especially ones that have been neurally induced (NI), may provide a
      functional benefit in a wide range of neurological disorders. Recently, we
      developed a new method for the efficient generation of neural cells from human
      bone marrow (BM)-derived MSCs (hMSC). Neural induction was achieved by exposing
      cells simultaneously to chromatin-modifying agents and neural-inducing factors.
      When transplanted into injured spinal cords, these NI-hMSCs survived,
      differentiated, promoted tissue preservation, and significantly improved
      locomotor recovery of injured animals. In the current study, we sought to
      determine whether this methodological approach would be equally effective in
      generating neural-like cells from feline BM-derived MSCs (fMSC). Our long-term
      goal is to develop an autologous source of neural stem cells that can be used in
      cellular replacement therapies in large animal (feline) models of neurological
      disorders. Our results showed that fMSCs exhibited a neural morphology after 48
      72 h of neural induction. Immunocytochemistry, ELISA, Western blot, and real-time
      RT-PCR studies revealed a higher level of expression of several pluripotent and
      neural genes in NI-fMSCs, the majority of which were expressed in untreated fMSCs
      at relatively low levels. We concluded that the expression of pluripotency- and
      neural-associated genes in unmodified fMSCs make them more pliable for
      reprogramming into a neural fate by manipulation with chromatin modifying agents
      and neural inducing factors.

PMID- 21718103
TI  - Associations of ionizing radiation and breast cancer-related serum hormone and
      growth factor levels in cancer-free female A-bomb survivors.
AB  - Levels of exposure to ionizing radiation are increasing for women worldwide due
      to the widespread use of CT and other radiologic diagnostic modalities. Exposure
      to ionizing radiation as well as increased levels of estradiol and other sex
      hormones are acknowledged breast cancer risk factors, but the effects of whole
      body radiation on serum hormone levels in cancer-free women are unknown. This
      study examined whether ionizing radiation exposure is associated with levels of
      serum hormones and other markers that may mediate radiation-associated breast
      cancer risk. Serum samples were measured from cancer-free women who attended
      biennial health examinations with a wide range of past radiation exposure levels
      (N  =  412, ages 26-79). The women were selected as controls for separate case
      control studies from a cohort of A-bomb survivors. Outcome measures included
      serum levels of total estradiol, bioavailable estradiol, testosterone,
      progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth
      factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed
      using repeated-measures regression models fitted with generalized estimating
      equations. Geometric mean serum levels of total estradiol and bioavailable
      estradiol increased with 1 Gy of radiation dose among samples collected from
      postmenopausal women (17%(1Gy), 95% CI: 1%-36% and 21%(1Gy), 95% CI: 4%-40%,
      respectively), while they decreased in samples collected from premenopausal women
      (-11%(1Gy), 95% CI: -20%-1% and -12%(1Gy), 95% CI: -20%- -2%, respectively).
      Interactions by menopausal status were significant (P  =  0.003 and P < 0.001,
      respectively). Testosterone levels increased with radiation dose in
      postmenopausal samples (30.0%(1Gy), 95% CI: 13%-49%) while they marginally
      decreased in premenopausal samples (-10%(1Gy), 95% CI: -19%-0%) and the
      interaction by menopausal status was significant (P < 0.001). Serum levels of
      IGF1 increased linearly with radiation dose (11%(1Gy), 95% CI: 2%-18%) and there
      was a significant interaction by menopausal status (P  =  0.014). Radiation
      associated changes in serum levels of estradiol, bioavailable estradiol,
      testosterone and IGF1 were modified by menopausal status at the time of
      collection. No associations with radiation were observed in serum levels of
      progesterone, prolactin, IGFBP-3 or ferritin.

PMID- 21718104
TI  - Detection of chromosomal instability in bystander cells after Si490-ion
      irradiation.
AB  - There is increasing evidence that two of the biological effects associated with
      low-dose ionizing radiation, genomic instability and bystander responses, may be
      linked. To verify and validate the link between the two phenomena, the ability of
      Si490 ions (high-energy particles associated with radiation risk in space) to
      induce bystander responses and chromosomal instability in human bronchial
      epithelial (HBEC-3kt) cells was investigated. These studies were conducted at
      both the population and single cell level in irradiated and nonirradiated
      bystander cells receiving medium from the irradiated cultures. At the general
      population level, transfer of medium from silicon-ion (Si490)-irradiated cultures
      (at doses of 0.073 Gy, 1.2 Gy and 2 Gy) to nonirradiated bystander cells resulted
      in small increases in the levels of chromosomal aberrations at the first
      division. Subsequently, single cell clones isolated from irradiated and bystander
      populations were analyzed for the appearance of de novo chromosome-type
      aberrations after ~50 population doublings using mFISH. Both irradiated and
      bystander clones demonstrated chromosomal instability (as seen by the de novo
      appearance of translocations and chromosomal fragments), albeit to different
      degrees, whereas sham-treated controls showed relatively stable chromosomal
      patterns. The results presented here highlight the importance of nontargeted
      effects of radiation on chromosomal instability in human epithelial cells and
      their potential relevance to human health.

PMID- 21718105
TI  - Suppressive effects of continuous low-dose-rate gamma irradiation on diabetic
      nephropathy in type II diabetes mellitus model mice.
AB  - It has been proposed that the development of diabetic nephropathy is caused in
      large part by oxidative stress. We previously showed that continuous exposure of
      mice to low-dose-rate gamma radiation enhances antioxidant activity. Here, we
      studied the ameliorative effect of continuous whole-body irradiation with low
      dose-rate gamma rays on diabetic nephropathy. Ten-week-old female db/db mice, an
      experimental model for type II diabetes, were irradiated with low-dose-rate gamma
      rays from 10 weeks of age throughout their lives. Nephropathy was studied by
      histological observation and biochemical analysis of serum and urine. Antioxidant
      activities in kidneys were determined biochemically. Continuous low-dose-rate
      gamma radiation significantly increases life span in db/db mice. Three of 24
      irradiated mice were free of glucosuria after 80 weeks of irradiation.
      Histological studies of kidney suggest that low-dose irradiation increases the
      number of normal capillaries in glomeruli. Antioxidant activities of superoxide
      dismutase, catalase and glutathione are significantly increased in kidneys of
      irradiated db/db mice. Continuous low-dose-rate gamma irradiation ameliorates
      diabetic nephropathy and increases life span in db/db mice through the activation
      of renal antioxidants. These findings have noteworthy implications for radiation
      risk estimation of non-cancer diseases as well as for the clinical application of
      low-dose-rate gamma radiation for diabetes treatment.

PMID- 21718106
TI  - Trichostatin A modified histone covalent pattern and enhanced expression of
      pluripotent genes in interspecies black-footed cat cloned embryos but did not
      improve in vitro and in vivo viability.
AB  - Abstract The black-footed cat (BFC; Felis nigripes), one of the smallest wild
      cats, is listed as threatened. Interspecies somatic cell nuclear transfer (Is
      SCNT) offers the possibility of preserving endangered species. Development to
      term of interspecies BFC (Is-BFC) cloned embryos has not been obtained, possibly
      due to abnormal epigenetic reprogramming. Treatment of intraspecies cloned
      embryos with TSA improves nuclear reprogramming and in vitro and in vivo
      viability. In this study, we evaluated (1) whether covalent histone modifications
      differ between Is-BFC cloned embryos and their IVF counterparts, (2) the optimal
      TSA concentration and exposure times to modify the covalent histone patterns, (3)
      if TSA enhances in vitro and in vivo developmental competence of cloned embryos,
      and (4) expression of pluripotent genes. Results indicated that the covalent
      histone modifications of Is-BFC cloned embryos aberrantly differ from their DSH
      IVF counterpart embryos. Aberrant epigenetic events may be due partially to the
      inability of the DSH cytoplasm to modify the restrictive epigenetic marks of the
      BFC nuclei after somatic cell nuclear transfer (SCNT). Incomplete remodeling of
      the histone H3K9me2 in Is-BFC cloned embryos possibly contributes to abnormal
      expression of pluripotent genes and low embryonic development. Treatment of Is
      BFC cloned embryos with TSA remodeled the covalent pattern in H3K9ac and H3K9me2,
      resembling epigenetic patterns in IVF counterpart embryos, and resulted in
      activation of some pluripotent genes. However, genomic reprogramming of Is-BFC
      cloned blastocysts did not follow the same reprogramming pattern observed in DSH
      IVF embryos, and in vitro and in vivo developmental competence was not enhanced.

PMID- 21718107
TI  - Early senescence is not an inevitable fate of human-induced pluripotent stem
      derived cells.
AB  - Human-induced pluripotent stem cells (hiPSCs) are expected to become a powerful
      tool for regenerative medicine. Their efficacy in the use of clinical purposes is
      currently under intensive verification. It was reported that hiPSC-derived
      hemangioblasts had severely limited expansion capability due to an induction of
      early senescence: hiPSC-derived vascular endothelial cells (VECs) senesced after
      one passage and hiPSC-derived hematopoietic progenitor cells (HPCs) showed
      substantially decreased colony-forming activities. Here we show that early
      senescence is not an inevitable fate of hiPSC-derived cells. Applying our unique
      feeder-free culture methods for the differentiations of human embryonic stem
      cells (hESCs), we successfully generated VECs and HPCs from three lines of hiPSCs
      that were established by using a retrovirus vector system. All hiPS-derived VECs
      could be subcultured by 2:1~3:1 dilutions up to 10~20 passages, after which the
      cells underwent senescence. Among the three lines of hiPSCs, two lines generated
      HPCs that bore comparable granulocyte colony-forming units to those of hESCs.
      Moreover, one line effectively reproduced HPCs within the sac-like structures,
      the fields of in vitro hematopoiesis, as in the case of hESCs. Surprisingly,
      release of neutrophils into culture supernatant persisted even longer (~60 days)
      than the case of hESCs (~40 days). Thus, the problem of early senescence can be
      overcome by selecting appropriate lines of hiPSCs and applying proper
      differentiation methods to them.

PMID- 21718108
TI  - Utilization of human amniotic mesenchymal cells as feeder layers to sustain
      propagation of human embryonic stem cells in the undifferentiated state.
AB  - Human embryonic stem (ES) cells are usually maintained in the undifferentiated
      state by culturing on feeder cells layers of mouse embryonic fibroblasts (MEFs).
      However, MEFs are not suitable to support human ES cells used for clinical
      purpose because of risk of zoonosis from animal cells. Therefore, human tissue
      based feeder layers need to be developed for human ES cells for clinical purpose.
      Hereof we report that human amniotic mesenchymal cells (hAMCs) could act as
      feeder cells for human ES cells, because they are easily obtained and relatively
      exempt from ethical problem. Like MEFs, hAMCs could act as feeder cells for human
      ES cells to grow well on. The self-renewal rate of human ES cells cultured on
      hAMCs feeders was higher than that on MEFs and human amniotic epithelial cells
      determined by measurement of colonial diameters and growth curve as well as cell
      cycle analysis. Both immunofluorescence staining and immunoblotting showed that
      human ES cells cultured on hAMCs expressed stem cell markers such as Oct-3/4,
      Sox2, and NANOG. Verified by embryoid body formation in vitro and teratoma
      formation in vivo, we found out that after 20 passages of culture, human ES cells
      grown on hAMCs feeders could still retain the potency of differentiating into
      three germ layers. Taken together, our data suggested hAMCs may be safe feeder
      cells to sustain the propagation of human ES cells in undifferentiated state for
      future therapeutic use.

PMID- 21718109
TI  - Dynamic changes in epigenetic marks and gene expression during porcine epiblast
      specification.
AB  - Given the difficulties in establishing bona fide porcine embryonic stem cells, we
      considered it would be interesting to investigate histone modifications, X
      chromosome inactivation (XCI), deacetylation, DNA methylation, and gene
      expression around the time of inner cell mass (ICM) and epiblast formation in
      sexed embryos. We found that the porcine epiblast expressed lower levels of NANOG
      and C-MYC, of which, we speculate may be one indication for the difficulties in
      obtaining embryonic stem cells (ESCs) from the porcine embryonic epiblast. Our
      research revealed distinct expression of lineage-specific-, early gastrulation-,
      and pluripotency-associated genes between the E10 epiblast and trophectoderm and
      between sexes. We determined that H3K27me3 was hypermethylated in the E6 embryo
      and hypomethylated in the E10 epiblast. Interestingly, we also observed exclusive
      localization of H3K4me3 in the E6 ICM, which may be a key marker for early
      lineage segregation in the pig. We also observed that the methyltransferases of
      H3K4me3, H3K27me3 and H3K9me3 and the DNA methyltransferases differed between
      male and female E10 embryos, and between tissues. We consider that epigenetic
      mechanisms, which are modified by specific enzymes, may be important for both
      early lineage segregation events and XCI, and these may further effect the levels
      of downstream-targeted gene expression in the different sexes.

PMID- 21718110
TI  - Ovine oocytes vitrified at germinal vesicle stage as cytoplast recipients for
      somatic cell nuclear transfer (SCNT).
AB  - The development of embryos produced by somatic cell nuclear transfer (SCNT) using
      vitrified oocytes as cytoplast recipients has been reported in cattle but not in
      sheep. This study investigated the parthenogenetic development of ovine oocytes
      vitrified and thawed at the germinal vesicle (GV) stage, matured in vitro, and
      then activated using two activation protocols. The optimal activation protocol
      was then used to assess development when vitrified oocytes were used as cytoplast
      recipients for SCNT. No blastocysts were obtained from vitrified oocytes
      activated by CA+CHX/CB (calcium ionophore A23187 + cycloheximide, and
      cytochalasin B); in contrast, vitrified oocytes activated by Sr/CB (strontium
      chloride (SrCl(2)) + cytochalasin B) developed to blastocyst, although the number
      was significantly lower (p < 0.05) than in toxicity and control groups (3.8 vs.
      20.0 and 27.3%, respectively). In SCNT embryos, cleavage at both 24 and 48 h
      postactivation (31.0 vs. 55.1% and 48.0 vs. 85.0%) was significantly lower (p <
      0.05) in vitrified oocytes compared to controls. However, no significant
      differences were observed in the frequency of development to blastocyst (13.0 vs.
      23.4%), the number of hatched blastocysts (7.0 vs. 10.3%), total cell numbers
      (90.3 +/- 4.9 vs. 97.6 +/- 4.6), number of apoptotic nuclei (13.1 +/- 0.9 vs.
      13.2 +/- 1.4), or the proportion of diploid embryos (60.0 vs. 75.0%). This study
      demonstrates for the first time that ovine oocytes vitrified at the GV stage can
      be used successfully as recipient cytoplasts for SCNT.

PMID- 21718111
TI  - Exploring anti-TGF-beta therapies in cancer and fibrosis.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine, with
      important roles in maintaining tissue homeostasis. TGF-beta signals via
      transmembrane serine/threonine kinase receptors and intracellular Smad
      transcriptional regulators. Perturbed TGF-beta signaling has been implicated in a
      large variety of pathological conditions. Increased TGF-beta levels have been
      found in patients with cancer, fibrosis, and systemic sclerosis, and were
      correlated with disease severity. In cancer, TGF-beta mediates tumor invasion and
      metastasis by affecting both tumor cells and the tumor microenvironment including
      fibroblast activation and immune suppression. Furthermore, TGF-beta is a strong
      stimulator of extracellular matrix deposition. On the basis of these
      observations, small molecule inhibitors of the TGF-beta receptor kinases,
      neutralizing antibodies that interfere with ligand?receptor interactions,
      antisense oligonucleotides reducing TGF-beta expression, and soluble receptor
      ectodomains that sequester TGF-beta have been developed to intervene with
      excessive TGF-beta signaling activity in the aforementioned disorders. Here, we
      review the current state of anti-TGF-beta therapy in clinical trials.

PMID- 21718112
TI  - The influence of extrusion process on myo-inositol phosphate content and profile
      in snacks containing rye bran.
AB  - The analysis of phytates in extrudates containing rye bran was done by a
      colorimetric method with the Wade reagent. The changes in profiles of myo
      inositol phosphates indicate that, although no isomers with positive
      physiological functions (such as I(1,4,5)P3, I(1,2,3)P3 or I(1,3,4,5)P4) were
      formed, the beneficial impact of extrusion is the reduction of phytates, as
      compared to the raw material. The obtained snacks containing rye bran received
      acceptable to desirable sensory scores.

PMID- 21718113
TI  - Anthocyanin content and the activities of polyphenol oxidase, peroxidase and
      phenylalanine ammonia-lyase in lettuce cultivars.
AB  - Anthocyanin content and the activities of polyphenol oxidase (PPO), peroxidase
      (POD) and phenylalanine ammonia-lyase (PAL) and their relationships were
      determined in the leaves of six lettuce (Lactuca sativa L.) cultivars, exposed
      for 6 weeks to alternating three different day/night temperatures. Anthocyanin
      content was found to be highest at 20/13 degrees C, followed by 25/20 degrees C
      and 30/25 degrees C, showing accumulation of anthocyanin at low temperatures.
      Activities of PPO and PAL were also found to be highest at low day/night
      temperatures, whereas the POD activity was decreased at low day/night
      temperatures. The most significant positive correlation existed between
      anthocyanin content and PPO activity (r2 = 0.71). The results suggest that
      various day/night temperature regimes affect anthocyanin content and the
      activities of PPO, POD and PAL in lettuce.

PMID- 21718114
TI  - The taxonomy of telemedicine.
AB  - The purpose of this article is to present a taxonomy for telemedicine. The field
      has markedly grown, with an increasing number of applications, a variety of
      technologies, and newly introduced terminology. A taxonomy would serve to bring
      conceptual clarity to this burgeoning set of alternatives to in-person healthcare
      delivery. The article starts with a brief discussion of the importance of
      taxonomy as an information management strategy to improve knowledge sharing,
      facilitate research and policy initiatives, and provide some guidance for the
      orderly development of telemedicine. We provide a conceptual context for the
      proliferation of related concepts, such as telehealth, e-health, and m-health, as
      well as a classification of the content of these concepts. Our main concern is to
      develop an explicit taxonomy of telemedicine and to demonstrate how it can be
      used to provide definitive information about the true effects of telemedicine in
      terms of cost, quality, and access. Taxonomy development and refinement is an
      iterative process. If this initial attempt at classification proves useful,
      subject matter experts could enhance the development and proliferation of
      telemedicine by testing, revising, and verifying this taxonomy.

PMID- 21718115
TI  - Standardizing sepsis screening and management via a tele-ICU program improves
      patient care.
AB  - OBJECTIVE: This article evaluates the feasibility of a tele-intensive care unit
      (ICU) nurse-driven early identification and treatment process for severe sepsis
      patients in improving compliance to evidence-based practice. MATERIALS AND
      METHODS: Florence Nightingale identified that by using science, logic, and
      compassion to manipulate the patient care environment nurses could create the
      best possible conditions for healing to occur. Nurses in a tele-ICU used this
      premise to initiate a standardized screening and data collection program using a
      custom-built document sharing application that conformed to the Surviving Sepsis
      Campaign (SSC) criteria for identification and treatment of severe sepsis.
      RESULTS: The tele-ICU nurses performed 89,921 screens on 36,353 ICU admissions to
      161 ICU beds across a geographical range of 500 miles. Between January 1, 2006
      and December 31, 2008, tele-ICU nurses identified 5,437 patients as meeting the
      criteria for severe sepsis. Statistically significant increases in compliance
      with SSC's bundled care recommendations were realized during this study period
      with four initial elements: antibiotic administration increased from 55% in 2006
      to 74% in 2008 (p=0.001), serum lactate measurement increased from 50% to 66%
      (p=0.001), the initial fluid bolus of >= 20 mL/kg increased from 23% to 70%
      (p=0.001), and central line placement increased from 33% to 50% (p=0.001).
      CONCLUSIONS: A tele-ICU nurse-driven process can prompt earlier identification
      and improve compliance to evidence-based practice bundles for complex disease
      states such as severe sepsis.

PMID- 21718116
TI  - Application of health technology in humanitarian response: U.S. Military deployed
      health technology summit--a summary.
AB  - Disasters are unpredictable, occurring without notice. They have a devastating
      effect and forever change the people they affect. We have witnessed the
      devastation from several significant events in 2010 and 2011, including the
      horrendous earthquakes in Haiti, Chili, New Zealand, and Japan. In the Japanese
      earthquake, a tsunami caused significant destruction to property and, of special
      concern, nuclear power plants along the Pacific Ocean, which will likely have a
      lasting impact worldwide. In a number of these events, the U.S. Military is often
      called upon to provide some level of support to help in the immediate aftermath.
      In early 2010, a massive earthquake struck the island nation of Haiti. In the
      days that followed, there was a significant influx of help from both military and
      nongovernmental organizations (NGOs). Although the response was not coordinated
      in any significant way, there was, nevertheless, wide application of various
      technologies as never before. Aside for the need to respond rapidly and
      efficiently, the U.S. Military is especially interested in how to utilize
      technology in a better way both internally and with NGOs. In the fall of 2010,
      the U.S. Army's Telemedicine and Advanced Technology Research Center partnered
      with the American Telemedicine Association to bring together a group of experts
      from industry, government, and academia to assess the challenges and
      opportunities for applying technologies not only in combat missions but for
      humanitarian response as well. This article summarizes the "U.S. Military
      Deployed Health Technology Summit" held on September 29, 2010, in Baltimore,
      Maryland, highlighting significant points. It presents a balance of capabilities
      across a broad spectrum of technologies and will help the U.S. Military in
      defining a roadmap for research and development to strengthen its ability to
      respond in future disasters and humanitarian events.

PMID- 21718117
TI  - Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human
      milk-based products in feeding extremely premature infants.
AB  - OBJECTIVE: This study evaluated the cost-effectiveness of a 100% human milk-based
      diet composed of mother's milk fortified with a donor human milk-based human milk
      fortifier (HMF) versus mother's milk fortified with bovine milk-based HMF to
      initiate enteral nutrition among extremely premature infants in the neonatal
      intensive care unit (NICU). METHODS: A net expected costs calculator was
      developed to compare the total NICU costs among extremely premature infants who
      were fed either a bovine milk-based HMF-fortified diet or a 100% human milk-based
      diet, based on the previously observed risks of overall necrotizing enterocolitis
      (NEC) and surgical NEC in a randomized controlled study that compared outcomes of
      these two feeding strategies among 207 very low birth weight infants. The average
      NICU costs for an extremely premature infant without NEC and the incremental
      costs due to medical and surgical NEC were derived from a separate analysis of
      hospital discharges in the state of California in 2007. The sensitivity of cost
      effectiveness results to the risks and costs of NEC and to prices of milk
      supplements was studied. RESULTS: The adjusted incremental costs of medical NEC
      and surgical NEC over and above the average costs incurred for extremely
      premature infants without NEC, in 2011 US$, were $74,004 (95% confidence
      interval, $47,051-$100,957) and $198,040 (95% confidence interval, $159,261
      $236,819) per infant, respectively. Extremely premature infants fed with 100%
      human-milk based products had lower expected NICU length of stay and total
      expected costs of hospitalization, resulting in net direct savings of 3.9 NICU
      days and $8,167.17 (95% confidence interval, $4,405-$11,930) per extremely
      premature infant (p < 0.0001). Costs savings from the donor HMF strategy were
      sensitive to price and quantity of donor HMF, percentage reduction in risk of
      overall NEC and surgical NEC achieved, and incremental costs of surgical NEC.
      CONCLUSIONS: Compared with feeding extremely premature infants with mother's milk
      fortified with bovine milk-based supplements, a 100% human milk-based diet that
      includes mother's milk fortified with donor human milk-based HMF may result in
      potential net savings on medical care resources by preventing NEC.

PMID- 21718119
TI  - ANZJP this month.

PMID- 21718118
TI  - Influence of laser phototherapy (lambda660 nm) on the outcome of oral chemical
      carcinogenesis on the hamster cheek pouch model: histological study.
AB  - PURPOSE: This study aimed to evaluate, histologically, the effect of low-level
      laser therapy (LLLT) (lambda660 nm) on DMBA chemically induced lesions of the
      oral mucosa of hamsters. BACKGROUND DATA: Squamous cell carcinoma (SCC) is the
      most common neoplasm of the oral cavity. It is aggressive, highly proliferative,
      invasive, and metastatic. There is evidence that LLLT similarly affects neoplasic
      and non-neoplasic cells. METHODS: Cancerous lesions were induced on the cheek
      pouch of 15 golden Syrian hamsters by using DMBA 3 times a week for 8 weeks. At
      the end of the cancer induction (8 weeks), animals in G1 were killed and the
      presence of tumors confirmed. Animals in G3 were irradiated (lambda660 nm, 30 mW,
      CW, O=3 mm, area: 0.07 cm(2), 424 mW/cm(2), 133 sec, 56.4(2)J/ cm(2), 4J) at
      every other day for 4 weeks. G2 received no interventions for the same period.
      Samples were taken and underwent histological analysis by light microscopy.
      RESULTS: GI showed 100% well-differentiated SCC. G2 showed 20% moderately
      differentiated and 80% well-differentiated SCC. G3 showed 40% well
      differentiated, 40% poorly differentiated, and 20% moderately differentiated SCC.
      Significant differences (p=0.02) in the amount of well-differentiated SCC were
      seen between G1 and G3 and between G3 and G2 (p=0.04). Significant difference was
      also seen between G3 and G1 and G2 with regard to the amount of poorly
      differentiated tumors (p=0.04). CONCLUSIONS: It is concluded that LLLT, within
      the parameters used in the present study, caused a significant progression of the
      severity of SCC in the oral cavity of hamsters.

PMID- 21718120
TI  - Going forth in July? Off-label use in psychiatry.

PMID- 21718121
TI  - Pre-emptive intervention in psychosis: agnostic rather than diagnostic.

PMID- 21718122
TI  - Schizophrenia literacy among Chinese in Shanghai, China: a comparison with
      Chinese-speaking Australians in Melbourne and Chinese in Hong Kong.
AB  - OBJECTIVE: The study reported in this paper was aimed at developing understanding
      of schizophrenia-related knowledge and preferences surrounding professional help,
      medication, and treatment methods among Chinese living in Shanghai, China.
      METHOD: A multi-stage cluster sampling method in which participants were taken
      from six of the 20 districts in Shanghai was adopted for this study. The 522
      Shanghai Chinese participants were presented with a vignette describing an
      individual with schizophrenia before being asked questions designed to assess
      both their understanding of schizophrenia and their preferences surrounding
      professional help, medication, and treatment methods. A comparative approach was
      adopted to identify similarities and differences between our findings and those
      of two previous studies on the mental health literacy of Chinese living in
      Melbourne, Australia and Hong Kong, respectively. RESULTS: A lower percentage of
      Shanghai Chinese than Hong Kong Chinese and Australian Chinese could correctly
      identify the condition described in the vignette as a case of acute
      schizophrenia. Although a far lower percentage of Shanghai Chinese endorsed the
      use of counselling professionals, a much higher percentage of the same group
      endorsed Chinese medical doctors and herbal medication. A lower percentage of
      Shanghai Chinese endorsed 'lifestyle changes' as a strategy for dealing with
      schizophrenia than did Chinese subjects living in Australia and Hong Kong. On the
      other hand, a higher percentage of Shanghai residents endorsed psychiatric
      treatment and the traditional Chinese practices of 'eating nutritious food/taking
      supplements' than among the other two groups of Chinese. CONCLUSIONS: This study
      highlights the need for educating Chinese in Shanghai to improve their
      schizophrenia literacy. The contents of the education programmes will need to
      take into consideration the socially and culturally driven beliefs that may have
      been influencing the knowledge and preferences of Shanghai Chinese concerning
      professional help, medication, and treatment methods for people suffering from
      schizophrenia.

PMID- 21718123
TI  - Comparison of British national newspaper coverage of homicide committed by
      perpetrators with and without mental illness.
AB  - OBJECTIVE: Adverse newspaper reporting of mental illness and in particular,
      violence committed by a mentally ill person, is thought to contribute to stigma.
      However, violent events are also considered highly newsworthy by journalists. The
      aim of this study was to compare the likelihood of newspaper reporting for
      convicted perpetrators of homicide with and without a history of contact with
      mental health services. METHOD: A 12 month (April 2000-March 2001) cohort of 577
      homicide perpetrators with and without a history of contact with mental health
      services in England and Wales was examined. These cases were identified by the
      National Confidential Inquiry into Suicide and Homicide by People with Mental
      Illness. By examining 12 national newspapers, we compared the likelihood of
      reporting homicide perpetrators with and without mental illness. RESULTS: Under
      half (228 cases, 40%) of the homicide perpetrators were reported in at least one
      of the study newspapers. Under a fifth (94 cases, 16%) of perpetrators had a
      history of contact with mental health services and such previous contact did not
      increase the likelihood of newspaper reporting (odds ratio 1.0 (0.6-1.6)).
      CONCLUSIONS: Previous contact with mental health services did not influence the
      newsworthiness of a homicide perpetrator. The stigmatizing effect of reporting
      homicide by perpetrators with mental illness may relate more to the quality of
      reporting rather than selective over-reporting.

PMID- 21718124
TI  - Impact of mental health first aid training on pharmacy students' knowledge,
      attitudes and self-reported behaviour: a controlled trial.
AB  - OBJECTIVE: The aim of this study was to assess the impact of delivering Mental
      Health First Aid (MHFA) training for pharmacy students on their mental health
      literacy and stigma towards mental illness. METHODS: A non-randomized controlled
      design was used, with all third year pharmacy students at the University of
      Sydney (n = 272) in 2009 invited to participate in one of two MHFA training
      courses, each of 12 hours duration. Of these, 174 students applied for MHFA
      training, of whom 60 were randomly selected and offered MHFA training. Outcome
      measures that were completed by all participants in the MHFA and non-MHFA groups
      before and after the MHFA training included an evaluation of mental health
      literacy, the 7-item social distance scale, and 16 items related to self-reported
      behaviour. RESULTS: The survey instrument was completed by 258 participants at
      baseline (59 MHFA and 199 non-MHFA) and 223 participants at follow up (53 MHFA
      and 170 non-MHFA). The MHFA training improved the participants' ability to
      correctly identify a mental illness (p = 0.004). There was a significant mean
      decrease in total social distance of 2.18 (SD 3.35) p <0.001 for the MHFA group,
      indicating less stigmatizing attitudes. There were improvements in recognition of
      helpful interventions with participants' views becoming more concordant with
      health professional views about treatments for depression (p = 0.009) and
      schizophrenia (p = 0.08), and participants were significantly more confident (p <
      0.01) to provide pharmaceutical services to consumers with a mental illness
      following the training. CONCLUSION: This study demonstrated that MHFA training
      can reduce pharmacy students' mental health stigma, improve recognition of mental
      disorders and improve confidence in providing services to consumers with a mental
      illness in the pharmacy setting.

PMID- 21718125
TI  - The low pass rate in the RANZCP clinical examinations: is the exam the problem?
AB  - OBJECTIVES: The aim of this study was to examine the role of supervision during
      psychiatric training in ensuring that registrars are adequately trained to meet
      the standards of the RANZCP examinations and to consider the implications for
      improving examination pass rates. METHOD: Audiotaped recordings of 50 h of
      supervision involving six supervisors and thirteen trainees, obtained 2000-2003,
      were transcribed and analysed thematically in a qualitative study, informed by a
      postmodern, foucaultian perspective. RESULTS: Until an examination loomed,
      supervisors rarely required evidence of theoretical study or structured case
      presentations from their trainees. The examination and the examiners served to
      justify the supervisors requiring such discipline. This enabled the supervisors
      to remain in a supportive role, while requiring higher standards from trainees.
      Paradoxically, while requiring higher standards 'for the exam', trainees were
      told that the examiners expected nothing more than 'good psychiatric practice'.
      In presenting cases, the attributes of prioritization, thoughtfulness,
      conciseness and good timing were valued, as reported in both undergraduate and
      other postgraduate medical training. CONCLUSIONS: Much of supervision bore little
      relationship to preparation for college examinations until these were imminent.
      While the daily practice of trainees and supervisors continues to be at variance
      with the practices required to pass the examination (reflected by reference to
      'exam-style' and 'non-exam style' presentations) the pass rates will remain low.
      If we believe that the standard set in the examination is that required of a
      practising psychiatrist, change is required to supervision and daily practice
      standards to reflect these standards.

PMID- 21718126
TI  - Factors associated with length of stay and the risk of readmission in an acute
      psychiatric inpatient facility: a retrospective study.
AB  - OBJECTIVE: This study was to investigate factors influencing the length of stay
      and predictors for the risk of readmission at an acute psychiatric inpatient
      unit. METHOD: Two comparative studies were embedded in a retrospective cross
      sectional clinical file audit. A randomly selected 226 episodes of admissions
      including 178 patients during a twelve-month period were reviewed. A total of 286
      variables were collected and analysed. A case control study was employed in the
      study of length of stay. A retrospective cohort study was used to investigate the
      predictors for the risk of readmission. RESULTS: Logistic regression analyses
      showed that 10 variables were associated with length of stay. Seclusion during
      the index admission, accommodation problems and living in an area lacking
      community services predicted longer stay. During the follow-up period 82 patients
      (46%) were readmitted. Cox regression analyses showed 9 variables were related to
      the risk of readmission. Six of these variables increased the risk of
      readmission, including history of previous frequent admission, risk to others at
      the time of the index admission and alcohol intoxication. More active and
      assertive treatment in the community post-discharge decreased the risk of
      readmission. CONCLUSIONS: Length of stay is multifactorially determined.
      Behavioural manifestations of illness and lack of social support structures
      predicted prolonged length of stay. Good clinical practice did not necessarily
      translate to a shorter length of stay. Therefore, length of stay is predictable,
      but not readily modifiable within the clinical domain. Good clinical practice
      within the community following discharge likely reduces the risk of readmission.
      Quality of inpatient care does not influence the risk of readmission, which
      therefore raises a question about the validity of using the rate of readmission
      as an outcome measure of psychiatric inpatient care.

PMID- 21718127
TI  - Suicide risk factors for NSW.

PMID- 21718128
TI  - NMR structural inference of symmetric homo-oligomers.
AB  - Symmetric homo-oligomers represent a majority of proteins, and determining their
      structures helps elucidate important biological processes, including ion
      transport, signal transduction, and transcriptional regulation. In order to
      account for the noise and sparsity in the distance restraints used in Nuclear
      Magnetic Resonance (NMR) structure determination of cyclic (C(n)) symmetric homo
      oligomers, and the resulting uncertainty in the determined structures, we develop
      a Bayesian structural inference approach. In contrast to traditional NMR
      structure determination methods, which identify a small set of low-energy
      conformations, the inferential approach characterizes the entire posterior
      distribution of conformations. Unfortunately, traditional stochastic techniques
      for inference may under-sample the rugged landscape of the posterior, missing
      important contributions from high-quality individual conformations and not
      accounting for the possible aggregate effects on inferred quantities from
      numerous unsampled conformations. However, by exploiting the geometry of
      symmetric homo-oligomers, we develop an algorithm that provides provable
      guarantees for the posterior distribution and the inferred mean atomic
      coordinates. Using experimental restraints for three proteins, we demonstrate
      that our approach is able to objectively characterize the structural diversity
      supported by the data. By simulating spurious and missing restraints, we further
      demonstrate that our approach is robust, degrading smoothly with noise and
      sparsity.

PMID- 21718129
TI  - Do the prevalence and components of metabolic syndrome differ among different
      ethnic groups? A cross-sectional study among obese Malaysian adolescents.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of metabolic
      syndrome and the most common combination of cardiometabolic disorders among
      different ethnic groups of obese adolescents in Malaysia. RESEARCH DESIGN AND
      METHODS: A cross-sectional study among 335 obese adolescent boys and girls aged
      12-18 years from 10 randomly selected schools was conducted. After recording
      blood pressure and waist circumference (WC), a fasting blood sample was obtained
      and analyzed for glucose and lipids. Metabolic syndrome was diagnosed on the
      basis of adolescent metabolic syndrome criteria specified by National Cholesterol
      Education Program Adult Treatment Panel III if three of the five risk factors-
      hypertriglyceridemia, hyperglycemia, hypertension, low high-density lipoprotein
      C, and increased WC--were present. The prevalence among different ethnic groups
      was analyzed. RESULTS: The obesity rate among adolescents was 8.4%, and nearly
      one-third of the obese adolescents had metabolic syndrome. More than 90% of obese
      adolescents had at least one metabolic abnormality. Metabolic syndrome was more
      prevalent among obese boys (40.2%) compared to obese girls (17%). Boys had
      significantly higher mean WC and triglycerides and lower HDL-C (P value 0.0001).
      Increased WC and triglycerides and high blood pressure comprised the most
      prevalent (34.3%) risk factor combination followed by WC, low HDL, and high blood
      pressure (22.5%). Over all, Indians had the highest prevalence of metabolic
      syndrome (36.4%), followed by Chinese (33.8%) and Malays (27.4%). Elevated
      triglyceride levels were more prevalent among Chinese, hypertension among Malays,
      and the other three abnormalities among Indians. CONCLUSION: Indians had the
      highest prevalence of metabolic syndrome. Increased WC and triglycerides and high
      blood pressure comprised the most prevalent risk factor combination.

PMID- 21718130
TI  - Evaluation of prognostic values of clinical and histopathologic characteristics
      in diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisolone therapy.
AB  - The relationship between histopathologic characteristics and treatment outcomes
      in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab
      based immunochemotherapy needs re-evaluation. Patients with newly diagnosed DLBCL
      treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and
      prednisolone (R-CHOP) were evaluated with respect to clinical characteristics,
      treatment efficacy, and survival. Immunohistochemistry of bcl-2, CD10, bcl-6, and
      MUM-1 was performed and patients were sub-classified as germinal center B-cell
      like (GCB) or non-GCB type according to the Hans algorithm. There was no
      significant difference in overall survival (OS) between patients with GCB and
      those with non-GCB. Although there was no significant difference in OS between
      high-intermediate and high risk groups as classified by the standard
      International Prognostic Index (IPI; p = 0.50), all three groups with the revised
      IPI had a clear-cut separation for event-free survival and OS. The revised IPI
      better predicted survival than did the standard IPI in patients with DLBCL
      treated with R-CHOP. The Hans classification had no prognostic value.

PMID- 21718131
TI  - The complex interplay between folate metabolism and risk of acute lymphoblastic
      leukemia.

PMID- 21718132
TI  - Myeloma cell adhesion to bone marrow stromal cells confers drug resistance by
      microRNA-21 up-regulation.
AB  - The bone marrow microenvironment plays a role in myeloma cell proliferation and
      adhesion-mediated drug resistance. In this study, we investigated microRNA-21
      (miR-21) expression changes in myeloma cells that adhered to bone marrow stromal
      cells (BMSCs). In addition, we studied the synergistic effect of miR-21
      inhibition with dexamethasone (Dex), doxorubicin (Dox), or bortezomib (Bort) on
      myeloma cell survival. We found that up-regulation of miR-21 expression was
      partially driven by nuclear factor-kappaB (NF-kappaB) signaling via myeloma cell
      adhesion to BMSCs. We also confirmed that RhoB is a miR-21 regulation target
      gene. Moreover, miR-21 inhibition combined with cytotoxic drug Dex or Dox
      inhibited myeloma cell survival more effectively than either treatment alone.
      These results suggest that the regulatory mechanisms of miR-21 expression may be
      a promising target for fine-tuning anti-myeloma therapy.

PMID- 21718133
TI  - Antineutrophil cytoplasmic antibody-associated vasculitis in a patient with
      polycythemia vera after long-term hydroxyurea treatment.

PMID- 21718134
TI  - Population based study of prognostic factors and treatment in adult Burkitt
      lymphoma: a Swedish Lymphoma Registry study.
AB  - Burkitt lymphoma (BL) is a rare neoplasm constituting 1-2% of adult lymphomas.
      Our aims in this study were to establish prognostic factors for overall survival
      in adult BL and evaluate the efficacy of different chemotherapy regimens in a
      population based setting. The study population was collected from the Swedish
      Lymphoma Registry 2000-2010. During this period, 156 adult patients with BL were
      identified. In multivariate analysis, age and performance status (PS) were
      significant adverse prognostic factors for overall survival. A modified
      prognostic index, based on: age >40 years, PS >1, and lactate dehydrogenase >
      upper limit of normal (ULN) was proposed. Patients with a score of 0-1, 2, and 3
      were found to have a 2-year survival of 91.2%, 58.4%, and 27.5%, respectively.
      High-intensity regimens were associated with more favorable overall survival.
      Rituximab addition was not significantly associated with improvement in survival.
      A modified prognostic index may be valuable for adult BL, as proposed.

PMID- 21718135
TI  - Flow-cytometric minimal residual disease monitoring for chronic lymphocytic
      leukemia in the post-allogeneic transplant period.

PMID- 21718136
TI  - Multicenter study of subcutaneous alemtuzumab administered at reduced dose in
      patients with fludarabine-relapsed/refractory chronic lymphocytic leukemia: final
      analysis.
AB  - Optimal management of patients with relapsed/refractory chronic lymphocytic
      leukemia (CLL) has been the motive behind a large number of studies in recent
      years, and previous response, its duration, and development of clonal evolution
      appear to be the best indicators for the choice of a new regimen. Although
      alemtuzumab in relapsed/refractory CLL may be beneficial, the optimal dosage and
      risk of infection related to its use remain thus far deeply controversial issues.
      In this pilot phase II study we investigated the feasibility of, toxicity of, and
      response to alemtuzumab at a reduced dose (30 mg s.c. for 2 weeks and then once a
      week at extended intervals: every 2, 4, 6 weeks up to 1 year). The overall
      response rate was 95%, with 51% complete response. The complete response range
      was 55% in fludarabine-relapsed patients and 28% in patients with fludarabine
      refractory disease, without significant difference between the two groups. The
      regimen was well tolerated with mild toxicity and few cytomegalovirus (CMV)
      infections. With a median follow-up of 27 months, the overall survival (46% at 3
      years) appears to be similar to that with other regimens although with fewer
      adverse events. In conclusion, treatment with alemtuzumab at a reduced dose seems
      to be safe and increases the event-free survival of patients with
      relapsed/refractory CLL, compared with the standard dose. A randomized study
      comparing both regimens including a larger number of patients is warranted.

PMID- 21718137
TI  - Cytological and histological detection of amyloid deposits in bone marrow of
      patients affected by multiple myeloma.
AB  - We recently published a study aiming to verify the frequency of amyloid deposits
      in the bone marrow of patients with multiple myeloma (MM) who did not present any
      signs or symptoms of systemic amyloidosis, applying the Congo red technique on
      bone marrow smears obtained by aspiration from the posterior iliac spine. The
      results suggested that nearly 40% of patients affected by MM may have amyloid
      deposits in their bone marrow. Subsequently, this finding has not been confirmed
      by another study performed with histological specimens of bone marrow in a
      similar clinical setting. To explain this discrepancy, we performed a comparative
      study on the bone marrows of 36 patients affected by MM, evaluated by both
      cytological and histological techniques. The results of this study confirm the
      high frequency of amyloid deposits in the bone marrow of patients affected by MM
      when the analysis is made on cytological smears, and indicate that the presence
      of amyloid on marrow smears is confirmed by core biopsies simultaneously
      performed in only 25% of cases. Should further studies confirm our findings,
      cytological assessment could be considered a sensitive technique to detect bone
      marrow amyloid deposits.

PMID- 21718138
TI  - Presence of complex t(6;9;22;15) four-way chromosome rearrangement plus rare
      t(1;6) translocation with favorable response to imatinib therapy in chronic
      myelogenous leukemia.

PMID- 21718139
TI  - De novo B lymphoblastic leukemia/lymphoma in an adult with t(14;18)(q32;q21) and
      c-MYC gene rearrangement involving 10p13.

PMID- 21718140
TI  - Complete response induced by fotemustine given as single agent in a patient with
      primary central nervous system non-Hodgkin aggressive lymphoma relapsed after
      high-dose chemotherapy and autologous stem cell support.

PMID- 21718141
TI  - Tyrosine kinase inhibitor resistance in chronic myeloid leukemia cell lines:
      investigating resistance pathways.
AB  - There are three currently identified secondary resistance mechanisms observed in
      patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitors
      (TKIs). These are BCR-ABL kinase domain (KD) mutations, increased BCR-ABL
      expression, and overexpression of drug-efflux proteins (ABCB1 and ABCG2). To
      investigate the interplay between these three modes of resistance, three CML
      blast crisis cell lines (K562, its ABCB1-overexpressing variant K562 Dox, and
      KU812) were cultured in gradually increasing concentrations of imatinib to 2 MUM,
      or dasatinib to 200 nM. Eight imatinib- and two dasatinib-resistant cell lines
      were established. Two imatinib-resistant K562 lines both had increased BCR-ABL
      expression as the apparent mode of resistance. However, when a dasatinib
      resistant K562 culture was generated we observed gradually increasing BCR-ABL
      expression which peaked prior to identification of the T315I mutation. BCR-ABL
      overexpression followed by mutation development was observed in a further 4/10
      cell lines, each with different KD mutations. In contrast, three imatinib
      resistant K562 Dox lines exhibited only a further increase in ABCB1 expression.
      All TKI-resistant cell lines generated had increased IC(50) (dose of drug
      required to reduce phosphorylation of the adaptor protein p-Crkl by 50%) to
      imatinib, dasatinib, and nilotinib, regardless of which TKI was used to induce
      resistance. This suggests that currently available TKIs share the same
      susceptibilities to drug resistance.

PMID- 21718146
TI  - Trust in physician in relation to blame, regret, and depressive symptoms among
      women with a breast cancer experience.
AB  - Following a diagnosis of breast cancer women experience considerable distress and
      often present with elevated symptoms of depression. A woman's relationship with
      her oncologist, and particularly trust in the physician, might influence
      depressive symptoms, as well as emotional and cognitive reactions to medical
      decisions made concerning treatment. To assess these relationships, women
      currently undergoing treatment for breast cancer (n = 40) and women who had
      previously been treated for breast cancer (n = 74) were asked about (1) trust in
      their physician, (2) who they blamed for negative events during treatment, (3)
      who made the treatment decisions, (4) regret, and (5) depressive symptoms. As
      well, community participants (n = 146) without breast cancer were asked about
      trust in their physician, levels of depression, and questions regarding blame if
      they hypothetically had breast cancer. Depression was greatest among women in
      treatment, and trust in physician was greatest among women posttreatment.
      However, trust in physician was neither related to depressive symptoms, decision
      making, nor responsibility for presence of metastases/relapse. Paradoxically,
      greater trust in physician was related to increased blame of the doctor for other
      negative events that had occurred. Furthermore, depressive scores were higher
      among women who blamed their doctor for negative events in comparison to women
      who ascribed blame to no one. As well, individuals who blamed themselves for
      negative events reported greater regret than individuals who blamed no one. Thus,
      though a woman may not hold her physician directly responsible for health
      outcomes, this relationship may be important to consider in other aspects of her
      psychological well-being.

PMID- 21718149
TI  - Experimental evaluation and model assessment of coexistence of PAOs and GAOs.
AB  - The study evaluated the competition and co-existence of PAOs and GAOs in
      sequencing batch reactor (SBR) systems sustaining enhanced biological phosphorus
      removal (EBPR). The SBR operation used acetate as the sole external carbon source
      and covered a wide range of initial COD/P ratios between 6.5 to 25.9 g COD/g P. A
      mechanistic model, ASMGG, was adopted for this purpose, which basically
      incorporated model components and processes associated with GAO metabolism and
      glycogen metabolism of PAOs. Model calibration was successfully performed with
      the same set of stoichiometric and kinetic coefficients for all the acetate,
      phosphate, glycogen and PHA profiles obtained in different experiments.
      Interpretation of experimental results by means of model simulation indicated
      competition and co-existence of PAOs and GAOs within the EBPR process,
      numerically assessing the composition of the microbial community sustained and
      identifying the respective role and function of PAOs and GAOs on the fate of
      glycogen and PHA.

PMID- 21718150
TI  - Efficacy of lopinavir-ritonavir reduced dose in HIV-infected patients.

PMID- 21718151
TI  - First detection of the staphylococcal trimethoprim resistance gene dfrK and the
      dfrK-carrying transposon Tn559 in enterococci.
AB  - The trimethoprim resistance gene dfrK has been recently described in
      Staphylococcus aureus, but so far has not been found in other bacteria. A total
      of 166 enterococci of different species (E. faecium, E. faecalis, E. hirae, E.
      durans, E. gallinarum, and E. casseliflavus) and origins (food, clinical diseases
      in humans, healthy humans or animals, and sewage) were studied for their
      susceptibility to trimethoprim as determined by agar dilution (European Committee
      on Antimicrobial Susceptibility Testing) and the presence of (a) the dfrK gene
      and its genetic environment and (b) other dfr genes. The dfrK gene was detected
      in 49% of the enterococci (64% and 42% of isolates with minimum inhibitory
      concentrations of >=2 mg/L or <=1 mg/L, respectively). The tet(L)-dfrK linkage
      was detected in 21% of dfrK-positive enterococci. The chromosomal location of the
      dfrK gene was identified in one E. faecium isolate in which the dfrK was not
      linked to tet(L) gene but was part of a Tn559 element, which was integrated in
      the chromosomal radC gene. This Tn559 element was also found in 14 additional
      isolates. All combinations of dfr genes were detected among the isolates tested
      (dfrK, dfrG, dfrF, dfrK+dfrG, dfrK+dfrF, dfrF+dfrG, and dfrF+dfrG+dfrK). The gene
      dfrK gene was found together with other dfr genes in 58% of the tested
      enterococci. This study suggested an exchange of the trimethoprim resistance gene
      dfrK between enterococci and staphylococci, as previously observed for the
      trimethoprim resistance gene dfrG.

PMID- 21718152
TI  - Genetic changes in Tibet.

PMID- 21718156
TI  - Pulse oximetry at high altitude.
AB  - Pulse oximetry is a valuable, noninvasive, diagnostic tool for the evaluation of
      ill individuals at high altitude and is also being increasingly used to monitor
      the well-being of individuals traveling on high altitude expeditions. Although
      the devices are simple to use, data output may be inaccurate or hard to interpret
      in certain situations, which could lead to inappropriate clinical decisions. The
      purpose of this review is to consider such issues in greater detail. After
      examining the operating principles of pulse oximetry, we describe the available
      devices and the potential uses of oximetry at high altitude. We then consider the
      pitfalls of pulse oximetry in this environment and provide recommendations about
      how to deal with these issues. Device users should recognize that oxygen
      saturation changes rapidly in response to small changes in oxygen tensions at
      high altitude and that device accuracy declines with arterial oxygen saturations
      of less than 80%. The normal oxygen saturation at a given elevation may not be
      known with certainty and should be viewed as a range of values, rather than a
      specific number. For these reasons, clinical decisions should not be based on
      small differences in saturation over time or among individuals. Effort should
      also be made to minimize factors that cause measurement errors, including cold
      extremities, excess ambient light, and ill-fitting oximeter probes. Attention to
      these and other issues will help the users of these devices to apply them in
      appropriate situations and to minimize erroneous clinical decisions.

PMID- 21718157
TI  - Pro: most climbers develop subclinical pulmonary interstitial edema.

PMID- 21718158
TI  - Con: most climbers do not develop subclinical interstitial pulmonary edema.

PMID- 21718159
TI  - Pro: rebuttal.

PMID- 21718160
TI  - Con: rebuttal.

PMID- 21718161
TI  - 'ome on the Range: altitude adaptation, positive selection, and Himalayan
      genomics.
AB  - In 2010, a number of papers were published describing data from genome-wide
      studies designed to identify genes and genetic variants that contribute (or
      contributed) to human adaptation to altitude in the Himalaya. The results were
      exciting, intriguing, and controversial. Several genes, most notably EGLN1 and
      EPAS1, were identified as strong candidates for a role in evolutionary adaptation
      to high altitude, and the time course over which this adaptation occurred was
      calculated by one team to be remarkably brief. Overall, the data suggest that, at
      least in the ancestors of the modern Tibetans, there was a powerful selective
      pressure favoring variants in genes central to the molecular response to hypoxia.
      The most obvious manifestation of this selection seems to be the Tibetan's well
      known blunted erythropoietic response to hypoxemia. This article briefly reviews
      recent developments in 'omic' analysis of Tibetan highland natives, with a focus
      both on the answers found and the questions raised.

PMID- 21718162
TI  - Peopling the Tibetan plateau: insights from archaeology.
AB  - Recent studies of the genome of modern Tibetans have revealed the existence of
      genes thought to provide an adaptive advantage for life at high elevation.
      Extrapolating from this discovery, some researchers now argue that a Tibetan-Han
      split occurred no more than 2750 yr ago. This date is implausible, and in this
      paper I review the archaeological data from the Tibetan plateau as one means by
      which to examine the veracity of this assertion. Following a review of the
      general state of knowledge of Tibetan prehistory, which is unfortunately only at
      its beginnings, I first examine the data that speak to the initial peopling of
      the plateau and assess the evidence that traces of their presence can be seen in
      modern Tibetans today. Although the data are sparse, both archaeology and
      genetics suggest that the plateau was occupied in the Late Pleistocene, perhaps
      as early as 30,000 yr ago, and that these early peoples have left a genetic
      signature in modern Tibetans. I then turn to the evidence for later migrations
      and focus on the question of the timing of the establishment of permanent settled
      villages on the plateau. Three areas of the plateau-northeastern Qinghai, extreme
      eastern Tibet, and the Yarlung Tsangpo valley-have evidence of permanent
      settlements dating from ca. 6500, 5900, and 3750 yr ago, respectively. These data
      are not consonant with the 2750 yr ago date for the split and suggest at a
      minimum that the plateau has been occupied substantially longer and, further,
      that multiple migrations at different times and from different places have
      created a complex mosaic of population history.

PMID- 21718163
TI  - Rapid recent human evolution and the accumulation of balanced genetic
      polymorphisms.
AB  - All evolutionary change can be traced to alterations in allele frequencies in
      populations over time. DNA sequencing on a massive scale now permits us to follow
      the genetic consequences as our species has diverged from our close relatives and
      as we have colonized different parts of the world and adapted to them. But it has
      been difficult to disentangle natural selection from many other factors that
      alter frequencies. These factors include mutation and intragenic reciprocal
      recombination, gene conversion, segregation distortion, random drift, and gene
      flow between populations (these last two are greatly influenced by splits and
      coalescences of populations over time). The first part of this review examines
      recent studies that have had some success in dissecting out the role of natural
      selection, especially in humans and Drosophila. Among many examples, these
      studies include those that have followed the rapid evolution of traits that may
      permit adaptation to high altitude in Tibetan and Andean populations. In some
      cases, directional selection has been so strong that it may have swept alleles
      close to fixation in the span of a few thousand years, a rapidity of change that
      is also sometimes encountered in other organisms. The second part of the review
      summarizes data showing that remarkably few alleles have been carried completely
      to fixation during our recent evolution. Some of the alleles that have not
      reached fixation may be approaching new internal equilibria, which would indicate
      polymorphisms that are maintained by balancing selection. Finally, the review
      briefly examines why genetic polymorphisms, particularly those that are
      maintained by negative frequency dependence, are likely to have played an
      important role in the evolution of our species. A method is suggested for
      measuring the contribution of these polymorphisms to our gene pool. Such
      polymorphisms may add to the ability of our species to adapt to our increasingly
      complex and challenging environment.

PMID- 21718164
TI  - Hypoxia: adapting to high altitude by mutating EPAS-1, the gene encoding HIF
      2alpha.
AB  - Living at high altitude is demanding and thus drives adaptational mechanisms. The
      Tibetan population has had a longer evolutionary period to adapt to high altitude
      than other mountain populations such as Andeans. As a result, some Tibetans
      living at high altitudes do not show markedly elevated red blood cell production
      as compared to South American high altitude natives such as Quechuas or Aymaras,
      thereby avoiding high blood viscosity creating cardiovascular risk. Unexpectedly,
      the responsible mutation(s) reducing red blood cell production do not involve
      either the gene encoding the blood hormone erythropoietin (Epo), or the
      corresponding regulatory sequences flanking the Epo gene. Similarly, functional
      mutations in the hypoxia-inducible transcription factor 1alpha (HIF-1alpha) gene
      that represents the oxygen-dependent subunit of the HIF-1 heterodimer, the latter
      being the main regulator of over 100 hypoxia-inducible genes, have not been
      described so far. It was not until very recently that three independent groups
      showed that the gene encoding HIF-2alpha, EPAS-1 (Wenger et al. 1997), represents
      a key gene mutated in Tibetan populations adapted to living at high altitudes
      (Beall et al. 2010 , Yi et al. 2010 , Simonson et al. 2010). Hypoxia-inducible
      transcription factors were first identified by the description of HIF-1 (Semenza
      et al. 1991 , 1992), which was subsequently found to enhance transcription of
      multiple genes that encode proteins necessary for rescuing from hypoxic exposure,
      including erythropoietic, angiogenic and glycolytic proteins. Then HIF-2 was
      identified (Ema et al. 1997 ; Flamme et al. 1997 ; Hogenesch et al. 1997 ; and
      Tian et al. 1997) and although it is highly similar to HIF-1 and has the
      potential to bind (Camenisch et al. 2001) and mediate (Mole et al. 2009) many of
      the same genes as HIF-1, its biological actions in response to hypoxia are
      distinct from those of HIF-1 (reviewed by Loboda et al. 2010). By now, several of
      these HIF-2 mediated processes have been implicated in the human response to high
      altitude exposure including erythropoiesis (Kapitsinou et al. 2010), iron
      homeostasis (Peyssonnaux et al. 2008), metabolism (Shohet et al. 2007; Tormos et
      al. 2010; Biswas et al. 2010 ; Rankin et al. 2009) and vascular permeability
      (Chen et al. 2009; Tanaka et al. 2005), among others. Clearly, mutation of EPAS-1
      has the potential to bring far more advantage when adapting to high altitude than
      solely mutating the Epo gene.

PMID- 21718165
TI  - Dexamethasone improves maximal exercise capacity of individuals susceptible to
      high altitude pulmonary edema at 4559 m.
AB  - We have previously demonstrated that prophylactic intake of dexamethasone
      improves maximal oxygen uptake (Vo(2)max) in high altitude pulmonary edema (HAPE)
      susceptible subjects 4 to 6 h after a 2-day climb to 4559 m. However, since with
      this ascent protocol HAPE usually develops after the first night at 4559 m or
      later, we hypothesized that a continued dexamethasone prophylaxis would result in
      an even more pronounced improvement of Vo(2)max after an additional night at high
      altitude. Vo(2)max of 24 HAPE susceptibles was evaluated on a bicycle ergometer
      at an altitude of 490 m and at 24 h after rapid ascent to 4559 m. Subjects were
      divided into two groups: The control group (n=14) performed both tests without
      dexamethasone, whereas the dexamethasone group (n=10) received dexamethasone 8 mg
      twice a day (b.i.d), starting 24 h prior to ascent. At 4559 m, Vo(2)max was 61%
      +/- 6% of the baseline value in the control group and 70% +/- 9% in the
      dexamethasone group (p=0.025). Similarly, O(2) pulse (Vo(2)/heart rate) was 68%
      +/- 7% and 77% +/- 11% of baseline, respectively (p=0.043). Arterial O(2)
      saturation at maximal exercise did not differ between groups, whereas at rest it
      was 83% +/- 10% in the control group and 91% +/- 4% in the dexamethasone group
      (p=0.009). Dexamethasone prophylaxis increased Vo(2)max of HAPE-susceptible
      individuals after the first night at 4559 m without affecting arterial O(2)
      saturation at maximal exercise. This might be explained by a sustained effect of
      dexamethasone on maximal cardiac output and pulmonary O(2) diffusion, both
      resulting in enhanced convectional O(2) transport to the locomotor muscles.

PMID- 21718166
TI  - Hemodynamics and metabolism at low versus moderate altitudes.
AB  - Despite the higher prevalence of diabetes and hypertension in populations
      residing at moderate altitudes, mortality in these populations is lower than in
      populations residing at low altitudes. To examine whether metabolic and
      hemodynamic differences can explain this apparent paradox, we performed a cross
      sectional study of a general population sample recruited in the Canary Islands,
      Spain (n=6729). We recorded altitude of residence, age, heart rate, blood
      pressure, body mass index, social class, physical activity, energy intake,
      alcohol intake, smoking habit, prevalence of type 2 diabetes mellitus and
      hypertension. In a subsample (n=903), we recorded serum concentration of
      cholesterol, triglycerides, glucose, C peptide, leptin, soluble leptin receptor
      (sObR), C-reactive protein, resistin, soluble CD40 ligand (sCD40L), and
      paraoxonase activity (PON), and we estimated insulin resistance and free leptin
      index. We found an inverse association between altitude and heart rate (p<0.001),
      leptin (p<0.001), free leptin index (p<0.001), resistin (p<0.001), and sCD40L
      (p<0.05) and a direct association between altitude and hypertension (odds
      ratio=1.29 for altitude >600 m; 95% confidence interval=1.03-1.62), glycemia
      (p<0.05), C peptide (p<0.001), insulin resistance (p<0.001), sObR (p<0.05), and
      PON (p<0.05). When social class was included in the multivariate model, the
      association with PON was no longer significant. In conclusion, individuals
      residing at moderate altitudes have a lower heart rate and lower serum
      concentration of total leptin, free leptin, and sCD40L. These differences may
      partially explain the lower mortality in these populations.

PMID- 21718167
TI  - Oxygen 2011.

PMID- 21718168
TI  - Culturing bovine nucleus pulposus explants by balancing medium osmolarity.
AB  - Regenerative therapies are promising treatments for early intervertebral disc
      degeneration. To test their efficacy, an in vitro tissue-level model would be
      valuable. Nucleus pulposus (NP) explant culture may constitute such a model, as
      the earliest signs of degeneration are in the NP. However, in NP explant
      cultures, balancing tissue osmolarity is crucial to preventing swelling,
      proteoglycan (PG) loss and, therefore, maintaining a native cell environment. In
      this study, we investigated the effect of medium osmolarity on NP explants. We
      hypothesized that balancing the inherent tissue osmolarity would prevent swelling
      and thus maintain NP tissue in a native state. Bovine NP explants were cultured
      for 21 days in hypo-, iso-, and hyper-tonic conditions using either sucrose or
      polyethylene glycol (PEG) to raise medium osmolarity. Explants were analyzed for
      water and biochemical content, cell viability, gene expression, and tissue
      histology, and compared to day 0 samples. In hypo-tonic and both sucrose
      cultures, swelling was not prevented, resulting in PG loss and changes in cell
      behavior. Only PEG cultures maintained water and biochemical content and a
      histological aspect similar to those of native tissue, with better results for
      hyper- than for iso-tonic conditions. Using PEG to raise culture medium
      osmolarity, we were able to maintain the NP tissue specific matrix composition,
      important for disc cell behavior. This approach, thus, constitutes a promising
      model to test regenerative therapies for early intervertebral disc degeneration.

PMID- 21718169
TI  - Targeted nanomedicine for detection and treatment of circulating tumor cells.

PMID- 21718170
TI  - Copolymer technology for advanced nanomedicine.

PMID- 21718171
TI  - News & views in ... nanomedicine.

PMID- 21718173
TI  - Conference Scene: nanomedicine kindles the development of the 'elixir of life'.
AB  - For the seventh time, nanomedicine experts from around the globe congregated in
      SAS Nagar, Punjab, for the Fourth Winter School on Nanotechnology in Advanced
      Drug Delivery, organized by the National Institute of Pharmaceutical Education
      and Research (NIPER), Mohali, India. The program covered almost all the
      scintillating areas of nanomedicine, including novel nanosystems for oral, ocular
      and transdermal drug delivery, nanostructured surfaces for medical applications,
      'smart' nanobullets for site-specific drug and gene delivery, designer
      nanoparticles for therapeutic delivery, tissue engineering and nanobiocomposites,
      cancer nanotherapy, and novel analytical and diagnostic tools. Special emphasis
      was given to the commercialization of nanomedical products, including issues
      related to intellectual property and risk management.

PMID- 21718174
TI  - Gold nanorod--siRNA induces efficient in vivo gene silencing in the rat
      hippocampus.
AB  - AIM: Gold nanorods (GNRs), cellular imaging nanoprobes, have been used for drug
      delivery therapy to immunologically privileged regions in the brain. We
      demonstrate that nanoplexes formed by electrostatic binding between negatively
      charged RNA and positively charged GNRs, silence the expression of the target
      housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) within the
      CA1 hippocampal region of the rat brain, without showing cytotoxicity. MATERIALS
      & METHODS: Fluorescence imaging with siRNA(Cy3)GAPDH and dark-field imaging using
      plasmonic enhanced scattering from GNRs were used to monitor the distribution of
      the nanoplexes within different neuronal cell types present in the targeted
      hippocampal region. RESULTS & CONCLUSION: Our results show robust nanoplex uptake
      and slow release of the fluorescent gene silencer with significant impact on the
      suppression of GAPDH gene expression (70% gene silencing, >10 days
      postinjection). The observed gene knockdown using nanoplexes in targeted regions
      of the brain opens a new era of drug treatment for neurological disorders.

PMID- 21718175
TI  - Attenuation of nontargeted cell-kill using a high-density lipoprotein-mimicking
      peptide--phospholipid nanoscaffold.
AB  - Research in the development of nanoscale drug carriers primarily focuses on
      maximizing drug delivery efficiency to tumor tissues. However, less attention has
      been given to minimizing drug toxicity to non-targeted cells to enhance
      therapeutic selectivity. AIM: Herein, we report on the use of a newly developed
      high-density lipoprotein-mimicking peptide-phospholipid nanoscaffold (HPPS) to
      deliver a lipophilic drug, paclitaxel oleate (PTXOL). METHOD & RESULTS: The
      formulated PTXOL HPPS (120:1) drastically increased therapeutic selectivity by
      reducing cytotoxicity of PTXOL to nontargeted cells. Using mice bearing targeted
      (KB) and nontargeted (HT1080) tumors as models, we demonstrated that tumor volume
      of nontargeted cells was decreased to 57% by PTXOL treatment but increased to
      1220% by PTXOL HPPS treatment. However, upon treatment of paclitaxel, PTXOL and
      PTXOL HPPS, tumor volumes of targeted groups were reduced to 85, 50 and 63%,
      respectively. CONCLUSION: These data strongly suggest that HPPS can attenuate
      toxicity of anticancer drugs to nontargeted cells, resulting in cell-killing
      efficacy only on targeted cells.

PMID- 21718176
TI  - Biomarker identification with ligand-targeted nucleoprotein assemblies.
AB  - AIMS: Since many biomarkers of both the tumor and its microenvironment are
      expected to involve differential expression of divalent proteins capable of
      protein or peptide ligand interaction, we are developing multivalent nanodevices
      for the identification of biomarkers in prostate cancer. PATIENTS & METHODS: We
      compared a multivalent thioredoxin-targeted nanodevice with monovalent
      thioredoxin in binding to human prostate cell line(s) and freshly frozen tissue
      specimens obtained after resection from patients with biopsy-proven prostate
      cancer. CONCLUSION: The nanodevice binds specifically with enhanced avidity to
      tumor microenvironment-associated stromal cells in prostate cancer tissue
      specimens. Cells that bind the nanodevice also reacted with antibodies to dimeric
      thioredoxin reductases 1 and 2, suggesting the utility of the nanodevice as a
      potentially specific and functional marker of tumor stromal cells.

PMID- 21718177
TI  - Self-assembled multifunctional nanoplexes for gene inhibitory therapy.
AB  - AIM: To enhance the stability of siRNA while improving their therapeutic
      properties and visualization at the target site, a novel nanoplex system was
      developed. MATERIALS & METHODS: The designed nanoplex system involved
      functionalizing siRNA with near-infrared quantum dots and loading them into
      histidylated glycol chitosan (GC-His). RESULTS: Colocalization studies revealed a
      twofold increase in siRNA uptake after encapsulation with GC-His and
      nanoparticles were localized in cytoplasm, suggesting that histidine promoted
      their dissociation from the endosomal membranes. Furthermore, as opposed to
      siRNAs treated with commercial transfection reagent, siRNAs loaded within GC-His
      showed a marked reduction (64%) of MDM2 protein expression 24 h after
      transfection. CONCLUSION: These findings concur that GC-His/siRNA-quantum dot
      nanoplexes are promising multifunctional vehicles for gene inhibitory therapy.

PMID- 21718178
TI  - Quantitative nanoparticle tracking: applications to nanomedicine.
AB  - Particle tracking is an invaluable technique to extract quantitative and
      qualitative information regarding the transport of nanomaterials through complex
      biological environments. This technique can be used to probe the dynamic behavior
      of nanoparticles as they interact with and navigate through intra- and extra
      cellular barriers. In this article, we focus on the recent developments in the
      application of particle-tracking technology to nanomedicine, including the study
      of synthetic and virus-based materials designed for gene and drug delivery.
      Specifically, we cover research where mean square displacements of nanomaterial
      transport were explicitly determined in order to quantitatively assess the
      transport of nanoparticles through biological environments. Particle-tracking
      experiments can provide important insights that may help guide the design of more
      intelligent and effective diagnostic and therapeutic nanoparticles.

PMID- 21718179
TI  - Role of nanomedicine in reversing drug resistance mediated by ATP binding
      cassette transporters and P-glycoprotein in melanoma.
AB  - Multidrug resistance (MDR) is one of the most common complex phenomenons
      exhibited by cancer cells. It is a very common property of melanoma
      postchemotherapy. MDR transporters, ATP binding cassette (ABC) transporters, play
      a critical role in conferring this property to melanoma cells. miRNA are post
      transcriptional regulators that regulate the expression of these ABC
      transporters. Targeting these miRNA, in turn targeting ABC transporters with the
      help of nanodelivery systems to overcome drug resistance, is the primary focus
      for attaining successful treatment methods for drug-resistant melanoma. These
      delivery systems are endocytosed by the cancer cells and do not require ABC
      transporters for their delivery, being a promising therapeutic measure for
      melanoma.

PMID- 21718181
TI  - Strategies and advances in nanomedicine for targeted siRNA delivery.
AB  - siRNA are a rapidly emerging class of new therapeutic molecules for the treatment
      of inherited and acquired diseases. However, poor cellular uptake and instability
      in physiological conditions limits its therapeutic potential, hence a need to
      develop a delivery system that can protect and efficiently transport siRNA to the
      target cells has arisen. Nanoparticles have been proposed as suitable delivery
      vectors with reduced cytotoxicity and enhanced efficacy. These delivery vectors
      form condensed complexes with siRNA which, in turn, provides protection to siRNA
      against enzymatic degradation and further leads to tissue and cellular targeting.
      Nanoparticles derived from polymers, such as chitosan and polyethylenimine have
      found numerous applications owing to ease of manipulation, high stability, low
      cost and high gene carrying capability. This article focuses on various aspects
      of nanomedicine based siRNA delivery with emphasis on targeted delivery to
      tumors.

PMID- 21718182
TI  - Future of nanomedicine: obstacles and remedies.
AB  - The future of nanomedicines is undermined by the lack of financial profitability,
      consumer distrust, ineffective regulation of new and generic products, weak
      patent protection and insurance market failure. Its economic breakthrough is
      dependent on a series of countervailing measures and actions. Success requires
      more investment induced by cost-effectiveness analyses and business plans based
      on clinical data, public education based on nanotoxicology studies, smart
      regulatory reform in the areas of testing, market entry and liability, effective
      and strategic patenting, patent dispute prevention and resolution, and innovative
      insurance policies.

PMID- 21718180
TI  - Nanoparticle PEGylation for imaging and therapy.
AB  - Nanoparticles are an essential component in the emerging field of nanomedical
      imaging and therapy. When deployed in vivo, these materials are typically
      protected from the immune system by polyethylene glycol (PEG). A wide variety of
      strategies to coat and characterize nanoparticles with PEG has established
      important trends on PEG size, shape, density, loading level, molecular weight,
      charge and purification. Strategies to incorporate targeting ligands are also
      prevalent. This article presents a background to investigators new to stealth
      nanoparticles, and suggests some key considerations needed prior to designing a
      nanoparticle PEGylation protocol and characterizing the performance features of
      the product.

PMID- 21718184
TI  - Evaluation of mesotherapeutic injections of three different combinations of
      lipolytic agents for body contouring.
AB  - BACKGROUND: There has been significant interest recently in the technique of
      mesotherapy as a method of 'melting fat' for body contouring. OBJECTIVE: The aim
      of this study was to evaluate the safety, efficacy and lipolytic potential of
      several compounds commonly used in cosmetic mesotherapy. METHODS: A total of 75
      women (mean age: 33 years) were separated randomly into three mesotherapy groups.
      Injections were performed for 15 treatments once a week. The main component of
      each cocktail was phosphatidylcholine/deoxycholic acid for group 1, caffeine for
      group 2, and Conjonctyl(r) for group 3. Outcome was evaluated by weight, body fat
      percentage (BFP), circumference measurements, and patient questionnaires.
      RESULTS: Seventy-two of all the patients (96%) showed a circumference loss. An
      average circumference reduction of 4.41 cm per site for group 1, 2.99 cm for
      group 2, and 2.10 cm for group 3 was achieved. Mean body circumference loss was
      statistically significant, with p < 0.00. Weight loss was 5.33 +/- 1.09 kg for
      group 1, 3.74 +/- 1.51 kg for group 2, and 2.82 +/- 1.43 kg for group 3. Seventy
      four subjects (98.7%) showed a BFP decrease. A questionnaire indicated high
      patient satisfaction (63%). No patient showed irregularities, dimples or any
      serious side effects after treatment. CONCLUSION: Mesotherapy is a well-tolerated
      and effective alternative treatment modality for reducing the diameter of body
      circumference.

PMID- 21718185
TI  - Effect of the 595-nm pulsed dye laser and ablative 2940-nm Er:YAG fractional
      laser on fresh surgical scars: an uncontrolled pilot study.

PMID- 21718186
TI  - Smartlipo MPXTM sculpting of the body and face.
AB  - Liposculpting of the body and face with the Smartlipo MPXTM has given excellent,
      predictable and long-lasting results. Since June 2009, a total of 72 patients
      have undergone liposuction with the Smartlipo MPX. Of these, the Smartlipo MPX
      has been used on the abdomen in 17 cases, on the thighs in 15, on the neck and
      jowls in 25, on the cheeks in six and has also been used on the arms, buttocks,
      and breasts. Results have been favorable and long-lasting with up to 17 months'
      follow-up. Laser sculpting of the face has significantly decreased the jowling
      seen with aging.

PMID- 21718187
TI  - Prevention of hemorrhagic complications after dental extractions into open heart
      surgery patients under anticoagulant therapy: the use of leukocyte- and platelet
      rich fibrin.
AB  - Leukocyte- and platelet-rich fibrin (L-PRF) is a biomaterial commonly used in
      periodontology and implant dentistry to improve healing and tissue regeneration,
      particularly as filling material in alveolar sockets to regenerate bone for
      optimal dental implant placement. The objective of this work was to evaluate the
      use of L-PRF as a safe filling and hemostatic material after dental extractions
      (or avulsions) for the prevention of hemorrhagic complications in heart surgery
      patients without modification of the anticoagulant oral therapy. Fifty heart
      surgery patients under oral anticoagulant therapy who needed dental extractions
      were selected for the study. Patients were treated with L-PRF clots placed into
      168 postextraction sockets without modification of anticoagulant therapy (mean
      international normalized ratio  =  3.16 +/- 0.39). Only 2 patients reported
      hemorrhagic complications (4%), all of which resolved a few hours after the
      surgery by compression and hemostatic topical agents. Ten patients (20%) showed
      mild bleeding, which spontaneously resolved or was resolved by minimal
      compression less than 2 hours after surgery. No case of delayed bleeding was
      reported. The remaining 38 patients (76%) showed an adequate hemostasis after the
      dental extractions. In all cases, no alveolitis or painful events were reported,
      soft tissue healing was quick, and wound closure was always complete at the time
      of suture removal one week after surgery. The proposed protocol is a reliable
      therapeutic option to avoid significant bleeding after dental extractions without
      the suspension of the continuous oral anticoagulant therapy in heart surgery
      patients. Other applications of the hemostatic and healing properties of L-PRF
      should be investigated in oral implantology.

PMID- 21718188
TI  - Using local culture and gender roles to improve male involvement in maternal
      health in southern Nigeria.
AB  - Group health talks were conducted in Ekiadolor, Southern Nigeria, to improve male
      attitudes and practices regarding their involvement in prenatal care and family
      planning. Intervention planners highlight the importance of embedding local
      cultural norms along with co-opting gendered beliefs for purposes of planning and
      implementing the group talks. The authors facilitated 9 groups of adult males
      mostly from the traditional hierarchy of the community. Using gender theory as an
      analytical lens along with the application of local cultural beliefs and norms, a
      useful communication intervention was developed that increased the possibility of
      positive male engagement in maternal health in 1 Nigerian community.

PMID- 21718189
TI  - NCDs: evidence abounds for action--The Moscow Declaration.

PMID- 21718191
TI  - Rinderpest eradicated. International organizations declare "cattle plague" dead.

PMID- 21718192
TI  - Questions conclusions in study of postoperative analgesia with buprenorphine.

PMID- 21718193
TI  - Veterinary public health in the age of "one health".

PMID- 21718194
TI  - What is your diagnosis? Hydrops fetalis.

PMID- 21718195
TI  - ECG of the month. Intermittent tachycardia-dependent left bundle branch block in
      a dog during anesthesia.

PMID- 21718196
TI  - What is the evidence? Diagnosis of an intracranial lesion as a meningioma on the
      basis of MRI characteristics.

PMID- 21718197
TI  - Pathology in practice. Gallbladder mucocele rupture, bile peritonitis,
      cholestasis, and liver inflammation and necrosis.

PMID- 21718198
TI  - Relationships between two categorical variables and between two noncategorical
      variables.

PMID- 21718199
TI  - Effect of the use of carprofen in dogs undergoing intense rehabilitation after
      lateral fabellar suture stabilization.
AB  - OBJECTIVE: To determine whether carprofen, a commercially available NSAID, would
      decrease perceived exertion and signs of pain in dogs and therefore increase
      muscle mass and hind limb function without decreasing range of motion after
      lateral fabellar suture stabilization. DESIGN: Randomized, blinded, controlled
      clinical trial. ANIMALS: 35 dogs with cranial cruciate ligament rupture and
      lateral fabellar suture stabilization followed by rehabilitation. PROCEDURES: All
      dogs underwent surgical stabilization of cranial cruciate ligament rupture by
      placement of a lateral fabellar suture. Dogs received carprofen (2.2 mg/kg [1
      mg/lb], PO, q 12 h) for the first 7 days after surgery and underwent concentrated
      rehabilitation exercises during weeks 3, 5, and 7 after surgery. Eighteen dogs
      also received carprofen (2.2 mg/kg, PO, q 12 h) during the weeks of concentrated
      rehabilitation. Outcomes were measured by a single investigator, who was blinded
      to group assignments, using pressure platform gait analysis, goniometry, thigh
      circumference, and mean workout speed at a consistent level of exertion. RESULTS:
      There were no differences between the 2 groups in ground reaction forces, thigh
      circumference, or exertion (mean workout speed) over time or at any individual
      time point. However, both groups improved significantly over time for all outcome
      measures. CONCLUSIONS AND CLINICAL RELEVANCE: Providing carprofen to dogs during
      concentrated rehabilitation after lateral fabellar suture stabilization did not
      improve hind limb function, range of motion, or thigh circumference, nor did it
      decrease perceived exertion, compared with control dogs. Carprofen was not a
      compulsory component of a physical therapy regimen after lateral fabellar suture
      stabilization.

PMID- 21718200
TI  - Evaluation of the sedative and cardiovascular effects of intramuscular
      administration of dexmedetomidine with and without concurrent atropine
      administration in dogs.
AB  - OBJECTIVE: To evaluate degree of sedation and cardiovascular, respiratory, acid
      base excess, and electrolyte variables in response to IM administration of
      dexmedetomidine or dexmedetomidine with atropine. DESIGN: Randomized crossover
      study. Animals-5 healthy 1- to 2-year-old sexually intact male Treeing Walker
      Coonhounds. PROCEDURES: Dogs were instrumented with catheters placed in the
      dorsal pedal artery and lateral saphenous vein. All dogs received dexmedetomidine
      (10 MUg/kg [4.5 MUg/lb], IM) or dexmedetomidine with atropine (0.02 mg/kg [0.009
      mg/lb], IM). Variables were measured at baseline (time 0) and 5, 15, 30, and 60
      minutes after drug administration. RESULTS: In all dogs, lithium dilution cardiac
      output decreased from a mean +/- SD baseline value of 5.07 +/- 1.0 L/min to 2.1
      +/- 0.9 L/min. Cardiac output was not different between dexmedetomidine group
      dogs and dexmedetomidine-atropine group dogs. Mean arterial pressure increased
      from baseline in both groups but was significantly higher in dexmedetomidine
      atropine group dogs, compared with dexmedetomidine group dogs. Heart rate in
      dexmedetomidine group dogs decreased from 110 +/- 14.2 beats/min to 49.4 +/- 10.4
      beats/min by 15 minutes. No differences were seen in blood gas values,
      electrolyte concentration, or hemoglobin values over time or between groups.
      Arrhythmias were detected in dexmedetomidine-atropine group dogs and included
      atrioventricular block, ventricular premature contractions, and ventricular
      bigeminy. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of atropine at 0.02
      mg/kg, IM, with dexmedetomidine at 10 MUg/kg, IM, resulted in an increase in mean
      arterial blood pressure and heart rate; deleterious cardiac arrhythmias were also
      observed. Use of atropine with dexmedetomidine is not recommended in dogs.

PMID- 21718201
TI  - Evaluation and comparison of outcomes in dogs with periarticular and
      nonperiarticular histiocytic sarcoma.
AB  - OBJECTIVE: To evaluate and compare the outcomes of dogs with periarticular
      histiocytic sarcoma (PAHS) and histiocytic sarcoma of other anatomic locations
      (non-PAHS) and identify factors associated with outcome for dogs with PAHS.
      DESIGN: Retrospective cohort study. ANIMALS: 19 dogs with PAHS and 31 dogs with
      non-PAHS. PROCEDURES: Medical records of dogs with histiocytic sarcoma that
      underwent definitive local treatment (surgery or radiation), chemotherapy, or a
      combination of these were reviewed. Patient signalment, clinical signs, staging
      test results, clinicopathologic data, type of treatment, response, and outcome
      were collected, and potential risk factors in dogs with PAHS were identified and
      analyzed for an association with outcome. RESULTS: Dogs with PAHS lived
      significantly longer than did dogs with non-PAHS, with an overall median survival
      times of 391 (range, 48 to 980) and 128 (range, 14 to 918) days, respectively,
      despite the presence of suspected metastasis at diagnosis in 13 of 19 dogs with
      PAHS. Dogs with PAHS without evidence of metastasis at diagnosis lived
      significantly longer than did dogs with PAHS with evidence of metastasis, with
      median survival times of 980 (range, 83 to 980) and 253 (range, 48 to 441) days,
      respectively. Administration of prednisone in dogs with PAHS was associated with
      a significantly shorter time to tumor progression (TTP) and increased risk of
      tumor progression and death. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that dogs with PAHS may have a favorable outcome independent of
      metastatic status when treated with chemotherapy or aggressive multimodal
      treatment. The concurrent administration of prednisone may be a negative
      predictive factor for survival time and TTP in dogs with PAHS.

PMID- 21718202
TI  - Radical excision with five-centimeter margins for treatment of feline injection
      site sarcomas: 91 cases (1998-2002).
AB  - OBJECTIVE: To evaluate outcomes of radical excision of feline injection-site
      sarcomas (ISS) via assessment of local recurrence and metastasis rates, survival
      times, and complications associated with surgery. DESIGN: Retrospective case
      series. ANIMALS: 91 cats with ISS. PROCEDURES: Medical records of cats that had
      radical excision of ISS without adjunctive treatment were reviewed. Information
      extracted included sex, type of surgical procedure, histologic tumor grade, tumor
      diameter, time from tumor detection to definitive surgery, complications
      associated with surgery, whether tumors recurred locally or metastasized, and
      survival times. Diagnosis of ISS was histologically confirmed, and additional
      follow-up was performed. RESULTS: Overall median survival time was 901 days.
      Thirteen of 91 (14%) cats had local tumor recurrence; 18 (20%) cats had evidence
      of metastasis after surgery. Median survival time of cats with and without
      recurrence was 499 and 1,461 days, respectively. Median survival time of cats
      with and without metastasis was 388 and 1,528 days, respectively. Tumor
      recurrence and metastasis were significantly associated with survival time,
      whereas other examined variables were not. Major complications occurred in 10
      cats, including 7 with incisional dehiscence. CONCLUSIONS AND CLINICAL RELEVANCE:
      Radical excision of ISS resulted in a metastasis rate similar to rates reported
      previously; the local recurrence rate appeared to be substantially less than
      rates reported after less aggressive surgeries, with or without adjuvant
      treatment. Major complication rates were similar to rates reported previously
      after aggressive surgical resection of ISS. Radical excision may be a valuable
      means of attaining an improved outcome in the treatment of feline ISS.

PMID- 21718203
TI  - Long-term outcome of dogs treated surgically for idiopathic chylothorax: 11 cases
      (1995-2009).
AB  - OBJECTIVE: To determine long-term outcome of dogs treated surgically for
      idiopathic chylothorax. DESIGN: Retrospective case series. ANIMALS: 11 client
      owned dogs with idiopathic chylothorax that underwent surgery between November
      1995 and April 2009 and had been followed up for at least 4 months after surgery.
      PROCEDURES: Medical records were reviewed for information on signalment, history,
      physical examination findings, results of clinicopathologic testing, radiographic
      findings, surgical procedures, postoperative complications, outcome, and cause of
      death. RESULTS: A median sternotomy was performed in 10 dogs, and a right
      intercostal thoracotomy (fifth and ninth intercostal spaces) was performed in 1.
      Thoracic duct ligation and subtotal pericardectomy were performed in all dogs.
      Thoracic omentalization was performed in 8 dogs at the time of surgery, passive
      pleuroperitoneal shunting was performed in 2 dogs, and pleurodesis was performed
      in 1 dog. Lung lobectomy was performed because of lung consolidation in 2 dogs
      and lung lobe torsion in another 2 dogs at the time of the initial surgery.
      Median disease-free interval did not differ significantly between dogs that did
      and did not undergo lung lobectomy. Postoperative complications occurred in 5
      dogs. Median follow-up time was 46 months. Eight of 11 dogs were free from
      clinical signs 5 years after surgery. Two of the 3 dogs that did not undergo
      thoracic omentalization had a recurrence of clinical signs. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that the prognosis for dogs surgically
      treated for idiopathic chylothorax was fair and that lung lobectomy was not a
      negative prognostic indicator.

PMID- 21718204
TI  - Anesthetic agents and complications in Vietnamese potbellied pigs: 27 cases (1999
      2006).
AB  - OBJECTIVE: To document complications associated with preanesthetic and anesthetic
      agents used in Vietnamese potbellied pigs and identify predictors of
      complications. DESIGN: Retrospective case series. ANIMALS: 27 potbellied pigs (14
      female and 13 male) ranging in age from 0.25 to 15 years old and ranging in body
      weight from 5.9 to 169 kg (13.0 to 371.8 lb) that were anesthetized on 32
      occasions between 1999 and 2006. PROCEDURES: Data, including perianesthetic
      management, anesthetic agents and dosages, complications, and outcome, were
      retrieved from medical records. Patient information, anesthetic agents, and
      duration of anesthesia were evaluated as predictors for development of
      complications. RESULTS: Anesthesia was maintained with isoflurane or sevoflurane
      during 30 anesthetic episodes. Commonly used premedicants were butorphanol,
      atropine, and midazolam administered in combination with xylazine or medetomidine
      and a combination of tiletamine-zolazepam and butorphanol. Anesthesia was induced
      with an inhalation agent on 15 occasions, via injection of ketamine on 10
      occasions, and via injection of propofol on 3 occasions. Complications included
      hypoventilation (16/24 [67%]), hypotension (16/25 [64%]), hypothermia (15/31
      [48%]), bradycardia (9/32 [28%]), and prolonged recovery time (7/32 [22%]). None
      of the factors evaluated were associated with development of these complications.
      All pigs survived anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that a variety of anesthetic agent combinations can be used to provide
      anesthesia in potbellied pigs with satisfactory outcomes. Although there were
      high incidences of hypoventilation, hypotension, and hypothermia, no specific
      anesthetic agent was associated with development of these complications.

PMID- 21718205
TI  - Diagnosis of presumed acute ischemic stroke and associated seizure management in
      a Congo African grey parrot.
AB  - CASE DESCRIPTION: A 14-year-old Congo African grey parrot (Psittacus erithacus
      erithacus) was evaluated for an acute onset of falling off of its perch and tonic
      clonic movements. CLINICAL FINDINGS: Clinical signs were consistent with partial
      seizures. Findings on whole-body radiography, CBC, and plasma biochemical
      analysis were unremarkable. Plasma magnesium, ionized calcium, and bile acids
      concentrations were within reference limits. A magnetic resonance imaging (MRI)
      examination of the head revealed the presence of a focal hyperintensity at the
      central to left side of the optic chiasm and a hyperintense focus in the right
      side of the midbrain area in T2-weighted and FLAIR pulse sequence images. These
      findings were most consistent with an acute ischemic stroke with 2 brain
      infarcts. TREATMENT AND OUTCOME: Seizures were initially managed with potassium
      bromide and phenobarbital administration. On the basis of poor results and
      difficulties to reach therapeutic blood concentrations, the treatment plan was
      changed to levetiracetam and zonisamide administration. Blood concentrations were
      monitored for both drugs, and the frequency of seizures substantially decreased
      thereafter. A follow-up MRI examination 2 months later revealed resolution of the
      hyperintense signals. During the 20-month follow-up period, subsequent clusters
      of seizures were managed by adjusting levetiracetam and zonisamide dosages and
      adding clonazepam and gabapentin administration to the treatment plan. Regression
      of intraparenchymal hyperintense lesions and improvement of clinical signs made a
      diagnosis of acute ischemic stroke most likely. CLINICAL RELEVANCE: Findings for
      this Congo African grey parrot indicated that an antemortem diagnosis of an acute
      ischemic stroke followed by long-term seizure management may be possible in
      affected psittacines.

PMID- 21718206
TI  - Relationship of in vitro minimum inhibitory concentrations of tilmicosin against
      Mannheimia haemolytica and Pasteurella multocida and in vivo tilmicosin treatment
      outcome among calves with signs of bovine respiratory disease.
AB  - OBJECTIVE: To determine associations between in vitro minimum inhibitory
      concentrations (MICs) of tilmicosin against Mannheimia haemolytica and
      Pasteurella multocida and in vivo tilmicosin treatment outcome among calves with
      clinical signs of bovine respiratory disease (BRD). DESIGN: Observational,
      retrospective, cohort study. ANIMALS: 976 feeder calves with clinical signs of
      BRD enrolled in 16 randomized clinical trials. PROCEDURES: Records of clinical
      trials from October 26, 1996, to November 15, 2004, were searched to identify
      calves with BRD from which a single isolate of M haemolytica or P multocida was
      identified via culture of deep nasal swab samples prior to treatment with
      tilmicosin (10 mg/kg [4.5 mg/lb], SC) and for which MICs of tilmicosin against
      the isolate were determined. The MICs of tilmicosin against recovered isolates
      and response to tilmicosin treatment were evaluated. RESULTS: Tilmicosin
      resistance among M haemolytica and P multocida isolates was uncommon (6/745
      [0.8%] and 16/231 [6.9%], respectively). Treatment outcome, defined as success or
      failure after tilmicosin treatment, did not vary with the MIC of tilmicosin
      against recovered isolates. The proportion of treatment failures attributed to M
      haemolytica isolates categorized as resistant (MIC of tilmicosin, >= 32 MUg/mL)
      or not susceptible (MIC of tilmicosin, >= 16 MUg/mL), was 0.2% and 0.5%,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Recovery of tilmicosin
      resistant M haemolytica or P multocida isolates was rare, and no association was
      detected between MIC of tilmicosin and treatment response.

PMID- 21718207
TI  - Sex differences in pharmacokinetics of cilostazol in rats.
AB  - The pharmacokinetics of cilostazol was investigated after oral and intravenous
      administration in both male and female rats. After oral administration, area
      under serum concentration-time curve (AUC) was about 35-fold higher in female
      rats than in male rats, and absolute bioavailability was about 5.8-fold higher in
      female rats than in male rats. Total body clearance (CL(total)) for female rats
      was around one-sixth of that for male rats. In vivo hepatic clearance (CL(h))
      calculated based on isolated liver perfusion studies was even higher than or
      around 90% of the in vivo CL(total) of cilostazol for female and male rats,
      respectively, indicating that cilostazol is mainly eliminated by the liver in
      both male and female rats. In vitro metabolism studies utilizing hepatic
      microsomes and recombinant cytochrome (CYP) isoforms clearly indicated that major
      metabolites of cilostazol were generated extensively with hepatic microsomes of
      male rats and that male-predominant CYP3A2 and male-specific CYP2C11 were mainly
      responsible for the hepatic metabolism of cilostazol. Therefore, the great sex
      differences in the pharmacokinetics of cilostazol were mainly attributed to the
      large difference in hepatic metabolism. Our experimental results also suggested
      that the substantial metabolism of cilostazol in the small intestine and its
      possible saturation would be responsible for dose-dependent bioavailability in
      both male and female rats.

PMID- 21718208
TI  - Associations of xenobiotic-metabolizing enzyme genotypes PON1Q192R, PON1L55M and
      CYP1A1*2A MspI with pathological symptoms of a rural population in south Greece.
AB  - Paraoxonases and cytochromes P450 constitute two major classes of xenobiotic
      metabolizing enzymes involved in the detoxification of pesticide chemicals. In
      this study, we examined the distribution of two common genetic polymorphisms of
      the paraoxonase 1 gene and one common polymorphism of the CYP1A1 gene, in
      relation to pathological diseases occurring in a rural population. Blood and hair
      samples were collected from 220 participants of an agricultural cohort in the
      south of Greece for genotype and pesticide analysis. Demographic information and
      disease status of the participants was obtained by questionnaire, medical
      examination and medical record. Organochlorine pesticides and metabolites (DDTs,
      HCHs) were extracted from hair and analyzed using gas chromatography combined
      with mass spectrometry techniques. Our results indicate exposure of the rural
      population of Amaliada to organophosphate and past exposure to organochlorine
      pesticides. Genotypic analysis of PON1Q192R, PON1L55M and CYP1A1*2A MspI
      polymorphisms was performed using PCR-RFLP. The PON1 192R and 55M alleles absence
      was significantly associated with hypertension (OR: 2.59; 95% CI: 1.10-6.09) and
      hepatitis (OR: 21.43; 95% CI: 2.53-181.50), respectively, as indicated from
      backward logistic regression. Although the presence of PON1 192R allele
      significantly affected the occurrence of prostate hyperplasia (OR: 0.35; 95% CI:
      0.03-0.40), no associations were obtained between the paraoxonase serum activity
      or the CYP1A1 genotype and the disease status.

PMID- 21718209
TI  - Is the digitization of laparoscopic movement using accessible alternative
      technologies possible?
AB  - It is widely documented that laparoscopic surgeons require training, and an
      objective evaluation of the training that they receive. The most advanced
      evaluation systems integrate the digitization of the movement of laparoscopic
      tools. A great number of these systems, however, do not permit the use of real
      tools and their high cost limits their academic impact. Likewise, it is
      documented that new and accessible systems need to be developed. The aim of this
      article is to explore the possibility of digitizing the movement of laparoscopic
      tools in a three-dimensional workspace, using accessible alternative technology.
      Our proposal uses a commercial Wii video game control in conjunction with a
      program for determining kinematic variables during the execution of a recognition
      task.

PMID- 21718210
TI  - Cancer stem cells in osteosarcoma: recent progress and perspective.
AB  - BACKGROUND: To review the current progress in osteosarcoma stem cells, including
      isolation and identification, special cell surface markers, relationship between
      drug-resistance and metastasis, and the involving signal pathways. METHODS: A
      review of the literature encompassing osteosarcoma stem cells was performed.
      RESULTS: Although the cancer stem cells hypothesis was first proposed about 50
      years ago, it is only in the last 10 years that advances in stem cell biology
      have provided increasing experimental evidence supporting this hypothesis. It has
      been postulated that within a tumor, a minor subpopulation of cells, termed
      cancer stem cells (CSC), drive the self-renewal and differentiation that account
      for the initiation, proliferation, metastasis, therapeutic resistance and
      recurrence of cancer. The CSC hypothesis opens up a novel conceptual approach for
      curing tumors that selectively kills CSCs, making it possible to eradicate
      cancer. Currently, osteosarcoma stem cells have been isolated and identified
      using various methods. Given the specific stem cell features, the study of CSCs
      has important implications in osteosarcoma prevention, detection and treatment,
      especially in curing early metastasis and preventing drug resistance. Focusing on
      their stem-like character, CSCs can be appropriately targeted by identifying
      links between the cells and their microenvironment. CONCLUSION: All of this
      research is in its infancy - many problems still exist. Further studies are
      needed to search for specific targeted therapies for osteosarcoma, in-depth study
      of mechanism of drug resistance, identifying the role that CSCs play in tumor
      metastasis, and demonstrate the imbalance of specific pathways in osteosarcoma
      stem cells.

PMID- 21718211
TI  - Long time persistence of residual 53BP1/gamma-H2AX foci in human lymphocytes in
      relationship to apoptosis, chromatin condensation and biological dosimetry.
AB  - PURPOSE: Novel assay for radiosensitivity is based on measurements of residual
      DNA repair foci produced by several proteins including phosphorylated H2AX (gamma
      H2AX), recombinase Rad51 (Rad51) and tumour suppressor p53 binding protein 1
      (53BP1), which co-localise with radiation-induced DNA double-strand breaks (DSB).
      Here, we studied dose-response for residual 53BP1, Rad51, and gamma-H2AX foci in
      relationship to apoptosis and chromatin condensation in human G(0)-lymphocytes.
      MATERIALS AND METHODS: Residual foci, apoptosis and condensation of chromatin
      were studied following irradiation with gamma-rays at doses of 0.5-10 Gy.
      RESULTS: No clear dose response for residual Rad51 was seen. Residual 53BP1/gamma
      H2AX foci remained in human lymphocytes up to four weeks after irradiation. No
      foci formed during radiation-induced apoptosis. We provide evidence that
      irreversible apoptotic condensation of chromatin is responsible for arrest of
      residual foci and preventing de novo focus formation. Similar linear dose
      dependences up to 2 Gy were observed for the 53BP1/gamma-H2AX foci at all studied
      time points. At higher doses, saturation and decline were caused by preferential
      elimination of apoptotic lymphocytes with residual foci. While primary 53BP1 and
      gamma-H2AX foci almost completely co-localised, co-localisation of residual foci
      did not exceed 17%, indicating that 53BP1 and gamma-H2AX proteins may remain for
      different times at the locations of DSB repair. CONCLUSIONS: Prolonged
      persistence of residual 53BP1/gamma-H2AX foci may be used for biological
      dosimetry within the dose range up to 2 Gy. While foci are not formed during
      radiation-induced apoptosis in human lymphocytes, elimination of apoptotic cells
      with residual foci may affect the dose response.

PMID- 21718212
TI  - Citalopram versus desipramine in treatment resistant depression: effect of
      continuation or switching strategies: a randomized open study.
AB  - OBJECTIVES. Evidence in favour of switching between selective serotonin reuptake
      inhibitor (SSRI) and tricyclic (TCA) antidepressants in treatment resistant
      depression has been tested in a few studies only, consequently a prospective
      study was undertaken to evaluate the impact of switching strategies. METHODS. One
      hundred eighty-nine patients who failed to respond to a previous antidepressant
      were randomised to four arms: firstly they received citalopram or desipramine for
      a 4-week period; secondly, those who failed to respond were treated for a further
      4-week period with the same antidepressant (citalopram-citalopram and desipramine
      desipramine arms) or switched to the alternate one (citalopram-desipramine and
      desipramine-citalopram arms). RESULTS. There was no difference in the first 4
      week phase between patients receiving citalopram versus desipramine in Hamilton
      Rating Scale for Depression (HRSD), Montgomery-Asberg Depression Rating Scale
      (MADRS), and Clinical Global Impression (CGI) scores. In the second 4-week phase
      remitter rates were higher among non-switched patients (P = 0.04). Moreover,
      considering HRSD and MADRS, switched patients reported significantly higher
      scores (P <= 0.02 for both scales at each time-point). CONCLUSIONS. This study
      supports the thesis that switching from an SSRI to a TCA (and vice versa) in non
      responders to a 4-week trial of an SSRI/TCA is not associated with improved
      response. The result goes in the opposite direction to that predicted by current
      guidelines.

PMID- 21718213
TI  - Inferential methods for comparing two single cases.
AB  - In neuropsychological single-case studies, it is not uncommon for researchers to
      compare the scores of two single cases. Classical (and Bayesian) statistical
      methods are developed for such problems, which, unlike existing methods, refer
      the scores of the two single cases to a control sample. These methods allow
      researchers to compare two cases' scores, with or without allowing for the
      effects of covariates. The methods provide a hypothesis test (one- or two
      tailed), point and interval estimates of the effect size of the difference, and
      point and interval estimates of the percentage of pairs of controls that will
      exhibit larger differences than the cases. Monte Carlo simulations demonstrate
      that the statistical theory underlying the methods is sound and that the methods
      are robust in the face of departures from normality. The methods have been
      implemented in computer programs, and these are described and made available (to
      download, go to http://www.abdn.ac.uk/~psy086/dept/Compare_Two_Cases.htm).

PMID- 21718214
TI  - Density pervades: an analysis of phonological neighbourhood density effects in
      aphasic speakers with different types of naming impairment.
AB  - We investigated the influence of phonological neighbourhood density (PND) on the
      performance of aphasic speakers whose naming impairments differentially implicate
      phonological or semantic stages of lexical access. A word comes from a dense
      phonological neighbourhood if many words sound like it. Limited evidence suggests
      that higher density facilitates naming in aphasic speakers, as it does in healthy
      speakers. Using well-controlled stimuli, Experiment 1 confirmed the influence of
      PND on accuracy and phonological error rates in two aphasic speakers with
      phonological processing deficits. In Experiments 2 and 3, we extended the
      investigation to an aphasic speaker who is prone to semantic errors, indicating a
      semantic deficit and/or a deficit in the mapping from semantics to words. This
      individual had higher accuracy, and fewer semantic errors, in naming targets from
      high- than from low-density neighbourhoods. It is argued that the Results provide
      strong support for interactive approaches to lexical access, where reverberatory
      feedback between word- and phoneme-level lexical representations not only
      facilitates phonological level processes but also privileges the selection of a
      target word over its semantic competitors.

PMID- 21718215
TI  - Action performance and action-word understanding: evidence of double
      dissociations in left-damaged patients.
AB  - It has been proposed that language and action representational systems overlap
      when the tasks used to assess them involve the same stimuli and require abilities
      acquired at similarly early developmental stage. We matched variables at task and
      stimulus level to test this hypothesis in a group of 12 left-damaged patients
      (and 17 controls). At the patients' group level, we replicated previously
      reported correlations between linguistic and nonlinguistic tasks. When
      performances were analysed individually, however, double dissociations were
      observed between the ability to imitate pantomimes and the ability to produce and
      comprehend the corresponding action verbs, as well as between the ability to use
      tools and the ability to comprehend the corresponding tool nouns. These findings
      suggest that processing action words is independent of the ability to produce the
      associated object-directed actions. Double dissociations were also found between
      the ability to comprehend action verbs and the ability to comprehend tool nouns.
      Moreover, action and tool naming showed differential effects of age of
      acquisition, suggesting that the two word categories meet the lexical
      organization by word class (nouns and verbs), even when related to identical
      action concept. Dissociations at behavioural level are supported by anatomical
      dissociations shown in the analysis of patients' lesions.

PMID- 21718216
TI  - TCDD and cancer: a critical review of epidemiologic studies.
AB  - The authors reviewed the epidemiologic studies on exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and cancer risk, published since the last full
      scale review made by the International Agency for Research on Cancer Monographs
      program in 1997. The update of a cohort of US herbicide producers generated
      negative results overall; the internal analysis provided evidence of an increased
      "all-cancer" risk in the highest exposure category, with a statistically
      significant exposure-response association in some of the many analyses performed.
      The update of a similar Dutch cohort did not confirm the previously observed
      association with TCDD exposure. The updated surveillance of the Seveso population
      provided evidence of increased all-cancer mortality 15-20 years after exposure
      among those living in the most contaminated area but might also reflect random
      variation, as overall excesses in the most recent follow-up were not observed.
      Corresponding data on cancer incidence offer little support to the mortality
      results. Updated results from cohort studies of Vietnam veterans potentially
      exposed to TCDD did not consistently suggest an increased risk of cancer. Results
      of additional, smaller studies of other occupational groups potentially exposed
      to TCDD, and of community-based case-control studies, did not provide consistent
      evidence of an increased cancer risk. In conclusion, recent epidemiological
      evidence falls far short of conclusively demonstrating a causal link between TCDD
      exposure and cancer risk in humans. The emphasis on results for overall cancer
      risk-rather than risk for specific neoplasms-is not justified on epidemiologic
      grounds and is not a reason for ignoring the weaknesses of the available
      evidence.

PMID- 21718217
TI  - Nuclear receptors as therapeutic targets for Alzheimer's disease.
AB  - INTRODUCTION: Alzheimer's disease (AD) is characterized by the accumulation and
      extensive deposition of amyloid beta (Abeta) in the parenchyma of the brain. This
      accumulation of amyloid is associated with perturbations in synaptic function,
      impairments in energy metabolism and induction of a chronic inflammatory response
      which acts to promote neuronal loss and cognitive impairment. AREAS COVERED:
      Currently, there are no drugs that target the underlying mechanisms of AD. Here,
      we propose a class of nuclear receptors as novel and promising new therapeutic
      targets for AD. This review summarizes the literature on nuclear receptors and
      their effects on AD-related pathophysiology. EXPERT OPINION: Nuclear receptors
      are attractive targets for the treatment of AD due to their ability to facilitate
      degradation of Abeta, affect microglial activation and suppress the inflammatory
      milieu of the brain. Liver X receptor agonists have proven difficult to move into
      clinical trials as long-term treatment results in hepatic steatosis. It is our
      view that PPAR-gamma activation remains a promising avenue for the treatment for
      AD; however, the poor BBB permeability of the currently available agonists and
      the negative outcome of the Phase III clinical trials are likely to diminish
      interest in pursuing this target.

PMID- 21718218
TI  - Executive function and memory in children with Fetal Alcohol Spectrum Disorder.
AB  - A complex relation exists between memory and executive functioning (EF),
      particularly when learning and recalling multifaceted or extensive information (
      Moscovitch & Winocur, 2002 ). A common instrument for evaluating this
      relationship is the Rey-Osterrieth Complex Figure (ROCF; Rey, 1941 ; Osterrieth,
      1944 ). The ROCF has proved particularly useful in pediatric research; however,
      little research has been conducted among children with Fetal Alcohol Spectrum
      Disorders (FASD). Seventy children (35 FASD, 35 control), aged 6 to 12 years,
      were tested using the ROCF. All participants with FASD had received a diagnosis
      according to the Canadian guidelines for FASD ( Chudley et al., 2005 ) using the
      4-digit diagnostic code ( Astley, 2004 ). Significant group differences were
      revealed with children with FASD demonstrating substantial difficulties in
      organization, accuracy, and memory. Among children with FASD, a distinctive
      profile emerged, lending support to the argument that children with FASD
      experience deficits in EF and memory throughout their development. Information
      from the present study will not only help to improve understanding of functioning
      in this population but also provide insight into how to deal with EF and memory
      deficits in terms of testing, treatment, and intervention.

PMID- 21718220
TI  - Growth differentiation factor 15 in cardiovascular diseases: from bench to
      bedside.
AB  - CONTEXT: Growth differentiation factor 15 (GDF-15) is a novel cytokine showing
      close association with cardiovascular diseases. The biological mechanism and
      clinical use of GDF-15 in cardiovascular diseases have been well demonstrated. We
      review recent investigations from both basic research and clinical trials into
      the biological role of GDF-15. METHODS: The data were obtained mainly from
      MedLine via PubMed and from our own investigations. RESULTS: Laboratory
      investigations revealed that GDF-15 has biphasic effects on cellular survival by
      several signaling pathways. GDF-15 participates in several cardiovascular
      pathological processes such as cardiac remodeling, ischemia/reperfusion injury
      and atherosclerotic plaque formation. As well, GDF-15 was found a prognostic
      biomarker of heart failure and acute coronary syndrome. The evidence for
      diagnostic or therapeutic utility is poor. CONCLUSION: GDF-15 has great potential
      as a biomarker in cardiovascular diseases, especially for prognosis, and is seen
      as a myocardial protective cytokine, but the exact mechanism of GDF-15 in
      cardiovascular diseases remains unknown.

PMID- 21718221
TI  - Multi-method assessment of mother-child attachment: links to parenting and child
      depressive symptoms in middle childhood.
AB  - This study included two different methods to assess mother-child attachment,
      questionnaires, and a doll play story stem interview, so their overlap could be
      evaluated. In addition, we investigated how attachment is related to parenting
      and child depression. The sample was comprised of 10- to 12-year-olds (N = 87)
      and their mothers. Children completed questionnaires (assessing security,
      avoidance, and ambivalence), and were administered a doll play interview to
      assess attachment patterns (security, avoidance, ambivalence, and
      disorganization). Two aspects of parenting (warmth/ engagement and psychological
      control) were assessed with child reports and observer ratings of maternal
      behavior. We also obtained child reports of depressive symptoms. Questionnaire
      and interview measures of attachment security were related to one another, and
      each showed predictable associations with parenting and child depression. By
      contrast, results were less consistent for the ambivalent and avoidant insecure
      attachment patterns, although disorganized attachment showed some associations
      with parenting and child adjustment.

PMID- 21718222
TI  - Attachment behavior and mother-child conversations as predictors of attachment
      representations in middle childhood: a longitudinal study.
AB  - This study examines longitudinal links between mother-child conversations and
      attachment patterns in early childhood and later attachment representations. It
      also tests the role of conversations as mediators in the association between
      behavioral security and attachment representations. Mother-child conversations
      (snack-time) and attachment behaviors (Separation-Reunion procedure) were
      assessed for 83 5.5-year-olds while attachment representations (attachment
      narratives) were measured at 8.5 years of age. Results showed correspondence
      between attachment behaviors and representations for secure-confident, ambivalent
      preoccupied, and disorganized/controlling-frightened groups. Affective quality of
      mother-child conversations predicted both child attachment behaviors and
      representations. Secure and confident children showed greater integration of
      affective information, ambivalent and preoccupied children more affect
      exaggeration, and disorganized/controlling and frightened children more chaotic
      conversations. Avoidant children tended to show more affect minimization in
      conversations. Finally, mother-child conversations centered on the sharing of
      emotions and thoughts mediated the relation between behavioral and
      representational attachment security, which underscores the importance of mother
      child conversations in the development of attachment representations in
      childhood.

PMID- 21718223
TI  - Narrative story stems with high risk six year-olds: differential associations
      with mother- and teacher-reported psycho-social adjustment.
AB  - Children's responses on a Narrative Story Stem Technique (NSST) were coded using
      scales reflecting essential attachment constructs, specifically, attachment,
      exploratory, sociability, and caregiving behavioral systems, as originally
      conceived by Bowlby ( 1973 , 1982 ) and elaborated upon by his followers
      (Cassidy, 2008 ). NSST responses were examined in relation to both mother- and
      teacher-reported psycho-social adjustment and risk using the MacArthur Health &
      Behavior Questionnaire (HBQ). Forty-six children participated (average age 6
      years 10 months), 19 of whom had high-risk backgrounds, and the rest
      demographically matched. Findings indicate that NSST scales were associated with
      behavior on certain HBQ scales, in expected directions. NSST responses appeared
      to differentiate socially competent children from children with the specific
      psycho-social risks of externalizing behavior problems and social isolation,
      according to mother-reports, on the one hand, and peer vulnerability and
      internalizing problems, according to teacher-reports, on the other. Implications
      for clinical applications are discussed.

PMID- 21718224
TI  - Attachment discontinuity in a high-risk sample.
AB  - In this study, we evaluated complex patterns of attachment discontinuity across
      time in 133 individuals from the Minnesota Study of Risk and Adaptation. In
      addition to individuals who were either insecure or secure across infancy, late
      adolescence, and adulthood (Stably Insecure and Stably Secure, respectively), we
      found three additional groups: Infant/Adolescent Secure, Infant/Adult Secure, and
      Infant-only Secure. Changes in attachment representations in these groups across
      time corresponded to stresses and supports in the socio-emotional context. The
      two groups classified as secure in adulthood (Stably Secure and Infant/Adult
      Secure) experienced more positive relationship-based outcomes than the other
      three groups. Our results suggest that continuity may be a reflection of a stable
      social context as much as it is an artifact of early working models, and
      illustrate "homeorhetic" pathways of development, in which not only the direction
      but the length of a developmental pathway can constrain future developmental
      trajectories.

PMID- 21718225
TI  - Pathways to earned-security: the role of alternative support figures.
AB  - This study explored the kinds of relationship experiences associated with earned
      security, i.e., the extent to which mothers who report early negative
      relationship histories with their parents are later able to form a secure working
      model of attachment (indicated by the ability to speak clearly and coherently
      about these histories). Mothers from a low-risk sample (N = 121) expecting their
      first child completed the Adult Attachment Interview (AAI), which was used to
      assess earned-security retrospectively using the stringent definition recommended
      by Main and Hesse (Hesse, 2008 ; Main, Goldwyn, & Hesse, 2002 ), as well as to
      identify alternative support figures. Participants also completed self-report
      measures of depressive symptomatology, questionnaires concerning their
      experiences in therapy, and later, when their babies were 12 to 15 months old,
      the Strange Situation procedure. Sixteen mothers were classified as earned-secure
      (25% of those classified as secure-autonomous and 13% of the whole sample). Women
      who were earned-secure (vs. insecure and continuous-secure) reported
      significantly higher levels of emotional support, but not instrumental support,
      from alternative support figures. They also spent more time in therapy than did
      insecure and continuous-secure women and were more likely to form secure
      attachments with their infants than insecure women. These findings were obtained
      even after controlling for depressive symptoms.

PMID- 21718226
TI  - Obituary for Leslie Henderson.

PMID- 21718227
TI  - Osteopontin: a potentially important therapeutic target in cancer.
AB  - INTRODUCTION: Cancer is an extremely complex disease and most cancer treatments
      are limited to chemotherapy, radiation and surgery. The progression of tumours
      towards malignancy requires the interaction of various cytokines, growth factors,
      transcription factors and effector molecules. Osteopontin is a cytokine-like,
      calcium-binding, extracelular-matrix- associated member of the small integrin
      binding ligand, N-linked glycoprotein (SIBLING) family of proteins. It plays an
      important role in determining the oncogenic potential of various cancers. The
      role of osteopontin in various pathophysiological conditions suggests that the
      alteration in post-translational modification result in different functional
      forms that might change its normal physiological functions. AREAS COVERED:
      Osteopontin -based anticancer therapy, which may provide a new insight for the
      effective management of cancer. EXPERT OPINION: A better understanding of the
      signalling mechanism by which osteopontin promotes tumourigenesis may be useful
      in crafting novel osteopontin -based anticancer therapy. The role of osteopontin
      in promoting cancer progression is the subject of in depth investigation and thus
      targeting osteopontin might be a suitable therapeutic approach for the treatment
      of cancer.

PMID- 21718228
TI  - Interventions following hearing screening in adults: a systematic descriptive
      review.
AB  - OBJECTIVE: Adult hearing screening may be a solution to the under-diagnosis and
      under-treatment of hearing loss in adults. Limited use and satisfaction with
      hearing aids indicate that consideration of alternative interventions following
      hearing screening may be needed. The primary aim of this study is to provide an
      overview of all intervention types that have been offered to adult (>= 18 years)
      screen-failures. DESIGN: Systematic literature review. Articles were identified
      through systematic searches in PubMed, EMBASE, Cinahl, the Cochrane Library,
      private libraries, and through reference checking. RESULTS: Of the initial 3027
      papers obtained from the searches, a total of 37 were found to be eligible. The
      great majority of the screening programmes (i.e. 26) referred screen-failures to
      a hearing specialist without further rehabilitation being specified. Most of the
      others (i.e. seven) led to the provision of hearing aids. Four studies offered
      alternative interventions comprising communication programme elements (e.g.
      speechreading, hearing tactics) or advice on environmental aids. CONCLUSIONS:
      Interventions following hearing screening generally comprised referral to a
      hearing specialist or hearing aid rehabilitation. Some programmes offered
      alternative rehabilitation options. These may be valuable as an addition to or
      replacement of hearing aid rehabilitation. It is recommended that this be
      addressed in future research.

PMID- 21718229
TI  - Masking level difference in an adaptive procedure for clinical investigation.
AB  - OBJECTIVE: Masking level difference (MLD) tests are an established component of
      auditory processing test batteries; however, normative data for these tests vary
      according to procedure. The purpose of this study was to establish a standardized
      procedure for clinical use in the measurement of the MLD. DESIGN: A newly
      developed computer software program using both an adaptive procedure (MLDA) and a
      Bekesy procedure (MLDB) was evaluated in this study. STUDY SAMPLE: Forty normal
      hearing, native-English speaking adults between the ages of 18 and 26 years were
      included in the study. RESULTS: Both the MLDA and MLDB procedures showed
      statistically significant sex differences in the masked thresholds used to obtain
      the MLD, but not for the calculated MLD value; hence, normative data need not be
      reported separately by sex. Furthermore, statistically significant differences
      between procedures were observed, with the MLDA procedure producing higher MLDs.
      The MLDA procedure permitted a d' analysis, which could not be determined using
      the MLDB procedure. For MLDA, d' = 1.4, test sensitivity = 96.4%, and test
      specificity = 60.3%. CONCLUSIONS: The results of this study indicate that MLDA is
      a more efficient testing procedure due to MLDA's higher MLD average and the
      statistical data available (d', and measures of sensitivity and specificity).

PMID- 21718230
TI  - Mini-review: Antimicrobial central venous catheters--recent advances and
      strategies.
AB  - Central venous catheters (CVCs) nowadays constitute critical devices used in
      medical care, namely in intensive care units. However, CVCs also represent one of
      the indwelling medical devices with enhanced risk of nosocomial device-related
      infection. Catheter-related infections (CRIs) are a major cause of patient
      morbidity and mortality, often justifying premature catheter removal and an
      increase in costs and use of resources. Adhesion and subsequent biofilm formation
      on the surfaces of indwelling catheters is elemental to the onset of
      pathogenesis. Seeking the prevention of CVC colonisation and CRI, a variety of
      approaches have been studied, tested and, in some cases, already applied in
      clinical practice. This review looks at the current preventive strategies often
      used to decrease the risk of CRIs due to colonization and biofilm formation on
      catheter surfaces, as well as at the more recent approaches under investigation.

PMID- 21718231
TI  - Pharmacotherapy and management strategies for coeliac disease.
AB  - INTRODUCTION: Coeliac disease is a common disease that affects approximately 1%
      of Northern European and American populations. Evidence suggests it is caused by
      an inappropriate immune response in genetically susceptible patients to dietary
      gluten found in wheat, rye, barley and, in a small minority of patients, oats.
      Treatment involves a lifelong gluten-free diet. This diet limits nutritional
      variety and is costly and difficult to maintain. AREAS COVERED: This review
      covers the current treatment options available and discusses novel emerging
      therapies for coeliac disease. EXPERT OPINION: Novel therapies are still in early
      stages of development and therefore, at present, a gluten-free diet remains the
      treatment of choice in coeliac disease due to its low side-effect profile. A
      replacement for a gluten-free diet would be superior to an adjunct; in this case
      dietary modification of gluten may well have the least side effects, be tolerated
      by a wider group of coeliac patients and therefore be accepted. Search terms
      used: Pubmed, Medline and clinicaltrials.gov were searched with 'celiac disease'
      and 'therapy' as MESH terms. Patent database was searched using the term 'celiac
      disease'. Conference attendance at DDW Chicago 2011 and Columbia 2010 was also
      used to gain further information from conference abstracts.

PMID- 21718232
TI  - Impact of indoleamine 2,3-dioxygenase on the antioxidant system in the placentas
      of severely pre-eclamptic patients.
AB  - Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme of the kynurenine
      pathway that degrades L-tryptophan, but a wider range of functions have now been
      proposed for this enzyme, including antioxidant activity. Our previous study
      revealed that reduced IDO expression in the placenta induces defective feto
      maternal immuno-tolerance leading to the onset of pre-eclampsia. In our present
      study, we assessed the effects of low placental IDO activity as an antioxidant.
      The placental levels of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a maker for
      oxidative damage to DNA, were significantly higher in pre-eclamptic than
      normotensive pregnancies (P<0.05). Immunohistochemical signals of 8-OHdG were
      detected mainly in syncytiotrophoblasts and vascular endothelial cells, and co
      localized with those for IDO. Furthermore, a significant inverse correlation was
      found between the IDO activity and 8-OhdG levels. These results show that
      oxidative stress is associated with decreased IDO activity in the pre-eclamptic
      placenta and suggest an impact of low IDO activity other than immune modulation
      in promoting the onset of this disorder.

PMID- 21718233
TI  - Progress of antiplatelet pharmacogenomics.
AB  - Numerous genetic variants have been studied in the context of antiplatelet
      responsiveness, particularly for aspirin and clopidogrel. The majority of these
      variants have failed to demonstrate any measurable level of clinical validity
      with the exception of the CYP2C19*2 allele. Several studies have identified a
      link between CYP2C19*2 carriers and decreased clopidogrel responsiveness as
      assessed by platelet reactivity testing and clinical outcomes. The FDA boxed
      warning and strong evidence of the CYP2C19*2 allele provide a compelling
      indication to alter treatment when genotype information is available. However,
      several questions remain and universal genotyping cannot be recommended at this
      time without further studies that establish the clinical utility of genomic
      testing for clopidogrel.

PMID- 21718234
TI  - Role of platelet function testing in clinical practice: current concepts and
      future perspectives.
AB  - Oral antiplatelet therapy is routinely administered to ACS patients as well as to
      patients undergoing percutaneous coronary intervention (PCI) with the primary aim
      of inhibiting platelet-mediated thrombus formation and subsequent abrupt vessel
      occlusion. Individual platelet response to aspirin and especially to clopidogrel
      is highly variable and evidence has grown in recent years linking an attenuated
      response to therapy with the occurrence of ischemic events. At present, the
      antiplatelet therapy landscape is changing with the emergence of prasugrel and
      ticagrelor as alternative and more potent treatment options. In addition, tests
      for near-patient monitoring of platelet function in clinical practice are
      available and are being increasingly employed for the optimization of
      antiplatelet treatment. It is hypothesized that platelet function testing may
      prove useful for achieving an optimized balance of proven platelet inhibition at
      a cost of moderate bleeding risk. This is also why first centers have already
      included testing in day-to-day routine. Extensive clinical evaluations with a
      range of currently-available assays for platelet function testing are ongoing and
      the current and future role of platelet function testing in clinical practice is
      a topic of much debate. Widespread adoption of this practice and its
      incorporation into clinical guidelines awaits the results of ongoing trials where
      treatment is changed based on platelet function testing data. This review paper
      summarizes the key characteristics of platelet function tests available, presents
      an overview of relevant studies and examines the present role of platelet
      function testing in clinical practice with a focus on antiplatelet therapy in
      patients undergoing coronary stent placement.

PMID- 21718235
TI  - Bleeding and acute coronary syndromes: defining, predicting, and managing risk
      and outcomes.
AB  - Acute coronary syndromes (ACS) continue to have a large impact on morbidity and
      mortality in the United States. Over the last two decades, there have been
      several advancements in the care of patients with ACS. The use of combined
      antiplatelet and anticoagulants and early invasive risk stratification in high
      risk patients has improved the rates of major adverse cardiovascular events.
      However, this treatment strategy increases the risk for bleeding. Studies have
      found an association between bleeding and subsequent mortality and morbidity in
      ACS patients; therefore, minimizing bleeding risk has become a priority. This
      review describes the prevalence of bleeding during ACS management, risk for
      bleeding, and strategies to reduce bleeding risk.

PMID- 21718236
TI  - Big science for small cells: systems approaches for platelets.
AB  - Platelets are dynamic blood cells that form life-threatening thrombi in response
      to a variety of pathological conditions such as atherosclerosis, diabetes,
      metastatic cancer, sickle cell disease and obesity. These thrombi can lead
      directly to myocardial infarction (MI), stroke and other thrombotic events that
      contribute to over a million deaths every year in the United States. Even though
      multiple, effective drugs have been developed to combat these pathologies by
      antagonizing platelet receptors and their ligands, clinical use of these drugs
      can result in serious bleeding consequences. With the advent of increasingly
      powerful and accessible systems biology approaches, however, new opportunities
      are available to identify novel platelet targets and elucidate potentially safer
      antiplatelet strategies. Here we provide an overview of some of these exciting
      systems approaches ranging from genomics to aptamer discovery and emphasize the
      importance of identifying and exploiting novel platelet targets for therapeutic
      benefit.

PMID- 21718237
TI  - Platelet and soluble glycoprotein VI - novel applications in diagnosis and
      therapy.
AB  - One of the key receptors involved in the prothrombotic stage of an acute coronary
      syndrome (ACS) is platelet glycoprotein VI (GPVI). This constitutively expressed
      collagen receptor is platelet-specific and has shown to be a useful biomarker
      tool for the early detection of atheroslerotic diseases such as ACS and ischemic
      stroke. In a multimarker panel of several biomarkers, platelet GPVI may
      contribute to risk stratification and prediction of clinical outcome in patients
      with symptomatic atherosclerotic diseases. Moreover, the soluble receptor of GPVI
      may also be an interesting and prospective target for molecular imaging to
      identify sites of vulnerable plaques as the results of preclinical studies
      suggest. Apart from the diagnostic use of platelet as well as soluble, plasmatic
      GPVI, therapeutical implications may be the blockade of collagen binding sides of
      GPVI, as platelet GPVI is not able to bind to collagen where the binding sides
      were already saturated with soluble GPVI. This therapeutic aspect could serve as
      a promising strategy for antithrombotic and antiatherosclerotic therapy in
      future.

PMID- 21718238
TI  - Current issues with glycoprotein IIb-IIIa antagonists.
AB  - The development of glycoprotein (GP) IIb-IIIa antagonists is reviewed with
      particular emphasis on the characteristics of each agent, the pharmacodynamic
      profile of each agent, results in pivotal clinical trials, and the associated
      implications. GP IIb-IIIa antagonists have greatest benefit when used as
      adjunctive therapy during percutaneous coronary intervention (PCI) when the
      patient has intra-coronary thrombosis. These agents appear to provide greatest
      benefit when used in combination with heparin. The clinical niche for parenteral
      GP IIb-IIIa antagonists is evolving but appears to be for patients in transition,
      such as individuals requiring emergent PCI before oral agents are fully active
      and for unstable patients requiring transport to PCI centers. Subsequent studies
      should evaluate the optimal duration of therapy with GP IIb-IIIa antagonists.

PMID- 21718239
TI  - Oral antiplatelet therapy for acute coronary syndromes: aspirin, P2Y12 inhibition
      and thrombin receptor antagonists.
AB  - The platelet is central to the pathophysiology of acute coronary syndromes (ACS)
      via its direct participation in the formation of the thrombotic occlusion and its
      participation in the coagulation cascade that results in the formation of
      thrombin. Antiplatelet therapy is a cornerstone of therapy in the setting of ACS.
      Unfortunately, many patients who receive intensive antiplatelet therapy remain at
      high risk for recurrent events. Current efforts to reduce this "residual risk"
      include lifestyle modifications, cardiac rehabilitation, and intensive therapy
      for dyslipidemia. Also being investigated are methods of individualizing and
      intensifying antiplatelet therapy. Novel compounds that promise to reduce
      recurrent ischemic events without an increase in bleeding events are being
      evaluated in clinical trials. This review summarizes ongoing efforts to improve
      the effectiveness of antiplatelet therapy among patients with ACS.

PMID- 21718240
TI  - Historical observations on the discovery of platelets, platelet function testing
      and the first antiplatelet agent.
AB  - An understanding of the historical paths that have lead to our current state of
      knowledge in the field of platelet studies can be both illuminating and
      inspiring. Considering that the existence and function of platelets were
      initially described just barely over 100 years ago it is exciting to recognize
      how far our knowledge has advanced in such a relatively short period of time.
      Within 20 years of Giulio Bizzozero's definitive description of blood platelets
      investigators began to develop tests that could quantitate the relationship
      between platelets, hemostasis and bleeding, and these tests have continued to be
      refined ever since. At the same time, and well before the role of platelets and
      antiplatelet agents in cardiovascular disease was appreciated, several clinicians
      started using aspirin for the prevention of heart attacks. All three of these
      paths of research - platelet biology, platelet function testing and antiplatelet
      therapies - all converge on what is arguably one of the most important questions
      in clinical medicine today: how to best prevent arterial thrombosis. For the
      current and future pioneers of platelet research an understanding of how we got
      to where we are today will hopefully allow for a clearer and inspired vision of
      where we will go next.

PMID- 21718241
TI  - Anti-platelet therapy.

PMID- 21718242
TI  - Safety and efficacy of tirofiban as adjunctive therapy for patients with ST
      elevation myocardial infarction: a comparison versus placebo and abciximab.
AB  - Tirofiban is a nonpeptide tyrosine derivative that together with eptifibatide
      (both small molecules) and abciximam belongs to the group of glycoprotein
      IIb/IIIa inhibitors. Though similar to abciximab in that it has a high affinity
      for the GP IIbIIIa inhibitor receptor, tirofiban dissociates from it much faster
      tan abciximab, what makes its action reversible in a few hours. Initially used
      upstream for treatment of patients with non ST-elevation acute coronary
      sindromes, recent evidence has shown its role as adjuntive therapy in patients
      with ST-elevation acute myocardial infarction treated with primary angioplasty
      when used at a higher dose. In this article, we performed a thorough and
      systematic review of randomized trials comparing tirofiban versus pacebo and
      tirofiban versus abciximab when used in this subset of patients. All these
      studies showed tirofiban to be a well tolerated and effective IIbIIIa inhibitor.
      When compared with placebo, tirofiban was associated with a significant reduction
      in mortality and myocardial infarction at one month, with a higher risk of minor
      bleeding in the follow-up. When compared with abciximab, tirofiban showed no
      difference in mortality and a tendency to higher rate of the composite of death
      and myocardial infarction in the short term follow-up that disappeared when only
      studies with high-dose tirofiban were considered. On the basis of the high-dose
      regimen, tirofiban may be considered useful in the management of patients with ST
      elevation myocardial infarction who undergo primary angioplasty.

PMID- 21718243
TI  - Mitochondria as a pharmacological target: a clue for efficacy and a reason for
      toxicity.

PMID- 21718244
TI  - Mitochondrial dysfunction and targeted drugs: a focus on diabetes.
AB  - Diabetes is a severe, heterogeneous, multifactorial, chronic disease. Diabetes
      and oxidative stress are related to continuous and acute overproduction of
      reactive oxygen species (ROS). These ROS are released principally from
      mitochondria, but also have other sources. Oxidative stress seems to play an
      important role in mitochondria-mediated disease processes, though the exact
      molecular mechanisms responsible remain elusive. ROS are necessary for the proper
      functioning of the cell, but their excessive production can be harmful, making
      antioxidant defenses essential. Some substances with antioxidant properties, such
      as vitamins C and E, have been used to eradicate the oxidative stress associated
      with diabetes. The results of clinical trials employing anti-oxidative stress
      reagents in patients with diabetes are contradictory, perhaps due to inadequate
      study design or the specific targets selected. This review considers the process
      of diabetes from a mitochondrial perspective and evaluates strategies currently
      under development for the targeted delivery of antioxidants or other molecules to
      mitochondria. The evidence compiled herein endorses the selective targeting of
      specific molecules to mitochondria as an effective strategy for modulating
      mitochondrial respiration and ROS production and protecting mitochondria against
      oxidative stress.

PMID- 21718245
TI  - Mitophagy and disease: new avenues for pharmacological intervention.
AB  - The process of intracellular macromolecular degradation known as macroautophagy
      has long been associated with the degradation of mitochondria. Recent studies
      have provided evidence that the process of mitochondria degradation via
      autophagy, now referred to as mitophagy, appears to be specifically targeted to
      mitochondria and highly regulated under both physiologic and pathologic
      conditions. This article provides a review of key developments in mitophagy
      research, including background information on the history, mechanisms, and
      regulation of macroautophagy, as well as discoveries that have enhanced our
      understanding of the specificity and independent regulation of mitophagy. This is
      followed by an analysis of how our current understanding of the mechanics and
      regulation of mitophagy may be exploited to yield pharmacological interventions
      for mitochondria-associated diseases. As yet, the potential for mitophagy-related
      pharmacological treatments for disease remains largely untapped. However, rapid
      progress in our understanding of both mitophagy and the pathology of mitochondria
      related diseases is leading us towards the convergence of science and medicine
      which will inevitably result in new and potent pharmacological therapies for the
      treatment of these maladies.

PMID- 21718246
TI  - New insights in drug-induced mitochondrial toxicity.
AB  - Drug-induced mitochondrial toxicity is rapidly gaining recognition within the
      pharmaceutical industry as a contributor to compound attrition and post-market
      drug withdrawals. This article describes the mechanisms which lead to drug
      induced mitochondrial toxicity, discusses high-throughput in vitro assays which
      are currently being used to identify mitochondrial dysfunction, and provides an
      overview on some of the drugs which impair mitochondrial function. While
      considerable progress has been made in the development of high-throughput assays
      to screen for mitochondrial impairment in vitro, much remains to be done. This
      includes the development of in silico models to predict drug-induced
      mitochondrial impairment, wider acceptance of suitable animal models,
      identification and validation of relevant biomarkers, and the translation of in
      vitro/in vivo results to clinical outcomes.

PMID- 21718248
TI  - Drug-induced cardiac mitochondrial toxicity and protection: from doxorubicin to
      carvedilol.
AB  - Mitochondria have long been involved in several cellular processes beyond its
      role in energy production. The importance of this organelle for cardiac tissue
      homeostasis has been greatly investigated and its impairment can lead to cell
      death and consequent organ failure. Several compounds have been described in the
      literature as having direct effects on cardiac mitochondria which can provide a
      mechanistic explanation for their toxicological or pharmacological effects. The
      present review describes one classic example of drug-induced cardiac
      mitochondrial toxicity and another case of drug-induced mitochondrial protection.
      For the former, we present the case for doxorubicin, an anticancer agent whose
      treatment is associated with a cumulative and dose-dependent cardiomyopathy with
      a mitochondrial etiology. Following this, we present the case of carvedilol, a
      beta-blocker with intrinsic antioxidant activity, which has been described to
      protect cardiac mitochondria from oxidative injury. The final part of the review
      integrates information from the previous chapters, demonstrating how carvedilol
      can contribute to reduce doxorubicin toxicity on cardiac mitochondria. The two
      referred examples result in important take-home messages: a) drug-induced cardiac
      mitochondrial dysfunction is an important contributor for drug-associated organ
      failure, b) protection of mitochondrial function is involved in the beneficial
      impact of some clinically-used drugs and c) a more accurate prediction of toxic
      vs. beneficial effects should be an important component of drug development by
      the pharmaceutical industry.

PMID- 21718249
TI  - Mitochondrial toxicity in HAART: an overview of in vitro evidence.
AB  - The combined antiretroviral therapeutic approach currently employed for the
      treatment of HIV infection, known as Higly Active Antiretroviral Therapy (HAART),
      has dramatically reduced AIDS-related morbidity and mortality. However, the
      adverse reactions associated with the long term use of this therapy have now
      become a major issue and researchers have focused on understanding the cellular
      mechanisms underlying these drug-induced detrimental effects which englobe a
      large list of different events including rash and hypersensibility reactions,
      hepatotoxicity, metabolic disturbances including lipodystrophy, and other
      metabolic syndrome-like disturbances such as hyperlactatemia, hyperlipedimia,
      insulin resistance and pancreatitis. Other events include CNS toxic effects,
      peripheral neuropathies as well as nephrotoxicity and increased risk of
      cardiovascular diseases. Many of these reactions have been shown to develop as e
      result of mitochondrial dysfunction. The mitochondrial effect of N(t)RTI
      (Nucleos(t)ide Reverse Transcriptase Inhibitors) class of drugs, which has been
      widely studied, is believed to originate from the inhibitory action of these
      drugs on DNA polymerase gamma, the enzyme responsible for replication of
      mitochondrial DNA. However, additional mitochondrial targets have also been
      described and need to be considered. As to NNRTI (Non-Nucleoside-Transcriptase
      Inhibitor) or PI (Protease Inhibitors), evidence of the implication of
      mitochondria has also been reported, however the details of the mechanisms
      underlying these actions are still not fully known. This review covers the
      current knowledge of mitochondrial toxicities, particularly the available in
      vitro evidence, regarding the most commonly used groups of HIV drugs. Novel
      findings of mtDNA-independent mitochondrial dysfunction have received special
      attention.

PMID- 21718250
TI  - Mitochondrial drug targets in cell death and cancer.
AB  - Mitochondria are involved in different physiological and pathological processes
      that are crucial for tumor cell physiology, growth and survival. Since cancer
      cells have frequently disrupted different cell death pathways that promote their
      survival, mitochondria may be key organelles to promote cell death in cancer
      cells. The present review is focused on the different experimental and
      therapeutic cancer strategies addressed to either target mitochondria directly,
      or use mitochondria as mediators of apoptosis. While the first group includes
      drugs that act on glycolysis, beta-oxidation, electron transport chain,
      mitochondrial permeability and the Bcl-2/IAP family protein, the second one
      consists of those drugs that cause cell death through the intrinsic apoptosis
      pathway by promoting ROS generation or by modulating mitochondrial protein
      involved in apoptosis induction.

PMID- 21718251
TI  - Principles and therapeutic relevance for targeting mitochondria in aging and
      neurodegenerative diseases.
AB  - Aging is a physiologic state in which a progressive decline of organ functions
      may be accompanied by developing age-related diseases and neurodegenerative
      diseases. The causes of such conditions remain unknown, being probably related to
      a multifactor process. To date, the Free Radical and Mitochondrial theories seem
      to be the two most prominent that could explain both how and why aged people
      develop certain disorders, providing a rationale for treatment. Several reports
      demonstrate that mitochondria play a key role in aging and some neurodegenerative
      diseases. Damaged mitochondria produce increased amounts of Reactive Oxygen
      Species (ROS), leading, in turn, to progressive augmentation in damage.
      Dysfunctional mitochondria enhance susceptibility to cell death. Indeed, at cell
      level mitochondria act as an energetic hub determining cell final fate through
      caspase-dependent apoptosis. Thus, if aging results from oxidative stress, it may
      be corrected by environmental, nutritional and pharmacological strategies. In
      this review we summarize the role of mitochondria dysfunction occurring in aging
      and neurodegenerative disease, describing novel mitochondria-targeted therapy
      approach and the new selective molecules and nanocarriers technology as
      potentially effective in targeting mitochondrial dysfunction.

PMID- 21718247
TI  - Mitochondrial therapeutics for cardioprotection.
AB  - Mitochondria represent approximately one-third of the mass of the heart and play
      a critical role in maintaining cellular function-however, they are also a potent
      source of free radicals and pro-apoptotic factors. As such, maintaining
      mitochondrial homeostasis is essential to cell survival. As the dominant source
      of ATP, continuous quality control is mandatory to ensure their ongoing optimal
      function. Mitochondrial quality control is accomplished by the dynamic interplay
      of fusion, fission, autophagy, and mitochondrial biogenesis. This review examines
      these processes in the heart and considers their role in the context of ischemia
      reperfusion injury. Interventions that modulate mitochondrial turnover, including
      pharmacologic agents, exercise, and caloric restriction are discussed as a means
      to improve mitochondrial quality control, ameliorate cardiovascular dysfunction,
      and enhance longevity.

PMID- 21718252
TI  - The uniqueness of the Trypanosoma cruzi mitochondrion: opportunities to identify
      new drug target for the treatment of Chagas disease.
AB  - Trypanosoma cruzi is the causative agent of Chagas' disease, which affects some 8
      - 10 million people in the Americas. The only two drugs approved for the
      etiological treatment of the disease in humans were launched more than 40 years
      ago and have serious drawbacks. In the present work, we revisit the unique
      characteristics of T. cruzi mitochondria and mitochondrial metabolism. The
      possibility of taking advantage of these peculiarities to target new drugs
      against this parasite is also discussed.

PMID- 21718253
TI  - Absence of cardiovascular disease risk factors in restless legs syndrome.
AB  - OBJECTIVE: Restless legs syndrome (RLS) might represent a condition at risk of
      cardiovascular (and cerebrovascular) disease; the role of sleep periodic leg
      movements, sleep deprivation, and presence of common risk factors for heart
      disease in these patients remains to be determined. The aim of this study was to
      evaluate the eventual presence of risk factors for cerebrovascular disease in
      RLS. MATERIALS & METHODS: Eighty-seven consecutive patients affected by
      idiopathic RLS were included in this study together with 81 controls. Blood
      count, chemistry, and kidney function tests were obtained. We detected subjects
      suffering from diabetes mellitus, kidney diseases, heart diseases, disk
      herniation, neuropathy, blood diseases, liver diseases, artery diseases,
      dyslipidemia, or hypertension. Polysomnography was recorded in 66 patients, and
      cerebral neuroimaging was obtained in 59 patients with RLS. RESULTS: None of the
      differences in blood test parameters was statistically significant; however,
      hypertension was found to be more frequent in controls and dyslipidemia was more
      frequent in patients with RLS, but this was explained by its higher frequency in
      patients also affected by obstructive sleep apnea. A diagnosis of cerebrovascular
      disease was posed for 14 patients with RLS (16.1%), but no predictive factor for
      its presence was found at the binomial logistic regression. CONCLUSION: Our
      findings argue against the presence of an altered lipid metabolism as a risk
      factor for the development of cerebrovascular disease in patients with RLS, even
      if they do support the idea that cerebrovascular disease might be frequent in
      this condition.

PMID- 21718254
TI  - Long-term follow up after uterine artery embolization for symptomatic uterine
      leiomyomas.
AB  - Uterine artery embolization is one of the established treatment options for
      symptomatic uterine leiomyomas, with a proven effect on the size of leiomyomas
      and providing short-term relief of symptoms. Only few studies have addressed long
      term satisfaction with the treatment. We conducted a historical cohort study of
      96 patients. The patients were treated at a median age of 43years (range 23
      59years). The median size of the largest myoma was 69mm (range 20-170mm). By use
      of a postal questionnaire (response rate 86%) and audit of patient files, we
      found that 53% reported full recovery of symptoms and 36% some effect on symptoms
      after a median of 8.9years (range 8-9.4years). Overall, 25% of the women reported
      a need for further treatment. The rate of eventual hysterectomy was 22%. We
      confirm that uterine artery embolization is a safe and well-tolerated procedure
      with a high long-term satisfaction rate.

PMID- 21718255
TI  - Radical trachelectomy versus radical hysterectomy for the treatment of early
      cervical cancer: a systematic review.
AB  - OBJECTIVE: To assess the efficacy and safety of radical trachelectomy (RT) and
      radical hysterectomy (RH) for patients with early cervical cancer. DESIGN:
      Systematic review with meta-analysis. POPULATION: Women who had early cervical
      cancer. METHODS: Prospective controlled clinical trials comparing RT with RH were
      identified using a predefined search strategy. Recurrence, five-year recurrence
      free survival rate, five-year overall survival rate, postoperative mortality,
      intraoperative and postoperative complications between the two operations were
      compared by using the methods provided by the Cochrane Handbook for Systematic
      Reviews of Interventions. RESULTS: Three controlled clinical trials involving 587
      participants were included. Meta-analysis showed that there was no significant
      difference between the two groups in recurrence rate [1.38; 95% confidence
      interval (CI) 0.58-3.28, p=0.47], five-year recurrence-free survival rate (1.17;
      95% CI 0.54-2.53, p=0.69), five-year overall survival rate (0.86; 95% CI 0.30
      2.43, p=0.78), postoperative mortality (1.14; 95% CI 0.42-3.11, p=0.80),
      intraoperative complications (1.66; 95% CI 0.11-25.28, p=0.72), postoperative
      complications (0.52; 95% CI 0.11-2.48, p=0.41), blood transfusion (0.29; 95% CI
      0.06-1.36, p=0.12) and number of harvested lymph nodes. However, RT, compared
      with RH, reduced blood loss and shortened duration to normal urine residual
      volume and postoperative hospital stay. Moreover, RT may achieve to normal
      conception rates, while RH makes patients sterile. CONCLUSIONS: Radical
      trachelectomy has similar efficacy and safety to RH as the surgical treatment for
      early cervical cancer. Moreover, it reduced blood loss and shortened the duration
      to normal urine residual volumes and postoperative hospital stay. Radical
      trachelectomy can be used to treat early stage cervical cancer as an alternative
      operation for patients who wish to preserve fertility.

PMID- 21718256
TI  - Cervical precancerous lesions--chromosomal instability in peripheral blood
      lymphocytes in relation to lesion stage, age and smoking habits.
AB  - OBJECTIVE: To evaluate chromosomal damage in peripheral blood lymphocytes (PBL)
      of patients newly diagnosed with cervical precancerous lesions with respect to
      age, smoking habits, miscarriages, abortions and lesion stage. DESIGN: Clinical
      study. SETTING: Clinic of Gynecology and Obstetrics in Kragujevac, Serbia, during
      2009-2010. POPULATION: The analyzed samples included 41 untreated patients aged
      24-65 years with a diagnosed low-grade squamous intraepithelial lesion (LSIL; 19
      patients) or a high-grade squamous intraepithelial lesion (HSIL; 22 patients).
      Control samples were obtained from 40 healthy women aged 24-53 years. METHODS:
      The frequency of micronuclei (MN) was estimated in circulating lymphocytes by
      using the cytokinesis-block micronucleus assay. MAIN OUTCOME MEASURE: The
      frequency of MN in PBL. RESULTS: The mean MN frequencies of both LSIL and HSIL
      patients were significantly higher than the MN frequency of healthy control
      women. There was no significant difference in MN frequency between LSIL and HSIL
      patients, between smokers and nonsmokers in both patient and control samples, or
      between miscarriage groups and abortion groups of patients. Considering
      confounder factors, age and health status influenced MN frequency. CONCLUSIONS:
      The results suggest that MN frequency in PBL of patients with cervical
      precancerous lesions corresponds to an increase of chromosomal damage,
      irrespective of smoking habits, miscarriages, abortions and lesion stages.

PMID- 21718257
TI  - Older mothers do not confer greater perinatal risk to dichorionic diamniotic
      twins.
AB  - Advanced maternal age may be associated with adverse maternal and perinatal
      outcomes in singleton pregnancies. It is unclear whether a similar association
      exists for dichorionic twins. This objective of this study was to ascertain
      whether advanced maternal age was associated with increased perinatal morbidity
      and mortality in a 15 year retrospective review of dichorionic diamniotic (DCDA)
      twins delivered at Queen Charlotte's and Chelsea Hospital, a tertiary referral
      center in London, UK, between 1994 and 2008. In all, 1 174 DCDA deliveries
      occurred in the study period. Maternal age was not associated with neonatal unit
      admission or composite fetal and neonatal mortality. Advanced maternal age
      appeared to have no deleterious effect on the perinatal outcomes of DCDA twin
      pregnancies.

PMID- 21718258
TI  - Anesthesia and postoperative delirium in older adults undergoing hip surgery.
AB  - OBJECTIVES: To examine the effects of general anesthesia on the risk of incident
      postoperative delirium in older adults undergoing hip surgery. DESIGN: Secondary
      analysis of haloperidol prophylaxis for delirium clinical trial data. Predefined
      risk factors for delirium were assessed prior to surgery. Primary outcome was
      postoperative delirium. Study outcome was compared across patient groups who
      received either general or regional anesthesia, and for individuals receiving
      various perioperative medications (benzodiazepines, anticholinergics, and
      opioids), using multivariable logistic regression after controlling for potential
      confounders. Subgroup analyses based on baseline cognitive impairment and
      delirium risk were also undertaken. SETTING: Large medical school-affiliated
      general hospital in Alkmaar, the Netherlands. PARTICIPANTS: Five hundred twenty
      six adults aged 70 and older undergoing hip surgery. MEASUREMENTS: The primary
      outcome was the incidence of postoperative delirium (Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method
      criteria). RESULTS: Sixty participants (11.4%) had incident postoperative
      delirium. One hundred eighty-nine (35.9%) received general anesthesia, 18 (9.5%)
      of whom developed postoperative delirium, and 337 (64.1%) received regional
      anesthesia, 42 (12.5%) of whom developed postoperative delirium (adjusted odds
      ratio=0.81, 95% confidence interval=0.43-1.52, P=.51). Results were stratified
      for baseline cognitive impairment, age, acute admission, perioperative medication
      and other delirium risk factors. Delirium was not independently associated with
      specific drugs or the medication classes opioids, benzodiazepines, and
      anticholinergics. CONCLUSION: General anesthesia has no distinct effect on
      incident postoperative delirium in older adults undergoing hip surgery. This also
      holds for individuals suffering from cognitive impairment or who are otherwise at
      risk for postoperative delirium. Perioperative use of narcotics, benzodiazepines,
      and anticholinergic agents was not associated with incident delirium in this
      cohort of older adults undergoing hip surgery.

PMID- 21718260
TI  - Outcomes of displaced and nondisplaced pelvic and sacral fractures in elderly
      adults.
AB  - OBJECTIVES: To identify fracture types in a series of older adults with pelvic
      fractures and to determine whether the type of pelvic fracture affected short
      term outcomes and morbidity. DESIGN: Retrospective chart review. SETTING:
      Teaching hospital. PARTICIPANTS: One hundred eighty-one individuals aged 65 and
      older with low-energy pelvic fractures. MEASUREMENTS: Fracture type, in-hospital
      complications, mortality, maximal return to function, and return to living
      situation. RESULTS: Of the 181 participants, 119 had unilateral displaced pubic
      rami fractures, 38 had nondisplaced pubic rami fractures, 14 had sacral
      insufficiency fractures, and 10 had bilateral displaced pubic rami fractures.
      There were no significant differences found in participant age; comorbidities;
      diagnosis of dementia; in-hospital complications; or 30-day, 90-day, or 1-year
      mortality rates between fracture types. Fracture type did not affect the ability
      of the participants to return home or their use of ambulatory aid. CONCLUSION:
      For older adults, morbidity and mortality rates for nondisplaced pubic rami
      fractures and sacral insufficiency fractures are similar to those for displaced
      pelvic fractures.

PMID- 21718259
TI  - A randomized controlled clinical trial of the Seattle Protocol for Activity in
      older adults.
AB  - OBJECTIVES: To compare the efficacy of a physical activity program (Seattle
      Protocol for Activity (SPA)) for low-exercising older adults with that of an
      educational health promotion program (HP), combination treatment (SPA+HP), and
      routine medical care control conditions (RMC). DESIGN: Single-blind, randomized
      controlled trial with two-by-two factorial design. SETTING: Community centers in
      King County, Washington, from November 2001 to September 2004. PARTICIPANTS: Two
      hundred seventy-three community-residing, cognitively intact older adults (mean
      age 79.2; 62% women). INTERVENTIONS: SPA (in-class exercises with assistance
      setting weekly home exercise goals) and HP (information about age-appropriate
      topics relevant to enhancing health), with randomization to four conditions: SPA
      only (n=69), HP only (n=73), SPA+HP (n=67), and RMC control (n=64). Active
      treatment participants attended nine group classes over 3 months followed by five
      booster sessions over 1 year. MEASUREMENTS: Self-rated health (Medical Outcomes
      Study 36-item Short-Form Survey) and depression (Geriatric Depression Scale).
      Secondary ratings of physical performance, treatment adherence, and self-rated
      health and affective function were also collected. RESULTS: At 3 months,
      participants in SPA exercised more and had significantly better self-reported
      health, strength, and general well-being (P<.05) than participants in HP or RMC.
      Over 18 months, SPA participants maintained health and physical function benefits
      and had continued to exercise more than non-SPA participants. SPA+HP was not
      significantly better than SPA alone. Better adherence was associated with better
      outcomes. CONCLUSION: Older adults participating in low levels of regular
      exercise can establish and maintain a home-based exercise program that yields
      immediate and long-term physical and affective benefits.

PMID- 21718261
TI  - Comparing antidepressant treatment patterns in older and younger adults: a claims
      database analysis.
AB  - OBJECTIVES: To compare depressed older (>=65) and younger (25-64) adults with
      regard to antidepressant treatment patterns and to assess factors associated with
      180-day nonpersistence. DESIGN: Retrospective matched cohort study. SETTING: U.S.
      managed care population. PARTICIPANTS: Older and matched younger adults diagnosed
      with depression and treated with antidepressants. MEASUREMENTS: Sociodemographic
      characteristics, comorbidities, polypharmacy, and characteristics of
      antidepressant treatment at 180 days were compared between older and younger
      adults. Analyses were conducted before and after the implementation of Medicare
      Part D on January 1, 2006, to consider the effect of this policy. RESULTS: Few
      participants received psychotherapy, especially older ones; rates were constant
      before and after 2006. Before 2006, older adults more frequently received
      antidepressants at lower (odds ratio (OR)=5.38, 95% confidence interval (CI)=3.57
      8.13) or intermediate dose (OR=2.42, 95% CI=1.93-3.02) and had poorer adherence
      to treatment (P<.001) than younger adults. After 2006, older adults received
      similar proportions of intermediate or high antidepressant doses as younger
      adults, but a lower dosage was still more likely to be prescribed (OR=1.87, 95%
      CI=1.09-3.20) and had higher treatment adherence (P<.001). Medication profile did
      not significantly affect the risk of nonpersistence, but increased with lower
      antidepressant dose (P<.001). Whereas nonpersistence was higher in older adults
      before 2006 (hazard ratio (HR)=1.25, 95% CI=1.22-1.46), the trend reversed after
      2006 (HR=0.76, 95% CI=0.66-0.88). CONCLUSION: More than half of participants with
      depression discontinued antidepressant treatment, and psychotherapy was rarely
      used. Implementation of Medicare Part D was associated with substantial changes
      in treatment of older adults with depression. The presence of comorbidities or
      polypharmacy was not associated with nonpersistence in depressed older adults.

PMID- 21718262
TI  - Educational outcomes from a novel house call curriculum for internal medicine
      residents: report of a 3-year experience.
AB  - Physician house calls are an important mode of healthcare delivery to frail
      homebound older adults and positively affect patient outcomes and learner
      education, but most physicians receive scant training in home care medicine. A
      novel longitudinal curriculum in house call medicine for internal medicine
      residents was implemented in July 2006, and educational outcomes were evaluated
      over the following 3 years. The 2-year curriculum included didactic and
      experiential components. Residents made house calls with preceptors and alone and
      completed a series of computer modules outlining knowledge essential to providing
      home-based care. They discussed the important features of the modules in
      regularly scheduled small groups throughout the 2-year experience, and each
      taught a "house call morning report" in their senior resident year. Evaluation
      methods included surveys before, during, and at the end of the 2-year curriculum
      (knowledge and attitudes); direct observation by preceptors during house calls
      (skills); and an online, anonymous survey at the end of each year (attitudes).
      Results show statistically significant increases in residents' knowledge, skills,
      and attitudes relevant to home care medicine. Residents describe educationally
      significant and positive effects from their house call experiences. This novel
      curriculum improved medical residents' knowledge, attitudes, and skills in
      performing house calls for frail elderly individuals. The longer-term outcomes of
      this intervention will continue to be studied, with the hope that it may be used
      to help provide educational opportunities to prepare the physician workforce to
      meet the service needs of a growing segment of the population.

PMID- 21718263
TI  - Association between insulin resistance and lean mass loss and fat mass gain in
      older men without diabetes mellitus.
AB  - OBJECTIVES: To examine the associations between insulin resistance and changes in
      body composition in older men without diabetes mellitus. DESIGN: Longitudinal
      cohort study of older men participating in the Osteoporotic Fractures in Men
      (MrOS) study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Three thousand
      one hundred thirty-two ambulatory men aged 65 and older at baseline.
      MEASUREMENTS: Baseline insulin resistance was calculated for men without diabetes
      mellitus using the homeostasis model assessment of insulin resistance (HOMA-IR).
      Total lean, appendicular lean, total fat, and truncal fat mass were measured
      using dual energy X-ray absorptiometry scans at baseline and 4.6 +/- 0.3 years
      later in 3,132 men with HOMA-IR measurements. RESULTS: There was greater loss of
      weight, total lean mass, and appendicular lean mass and less gain in total fat
      mass and truncal fat mass with increasing quartiles of HOMA-IR (P<.001 for
      trend). Insulin-resistant men in the highest quartile had higher odds of 5% or
      more loss of weight (odds ratio (OR)=1.88, 95% confidence interval (CI)=1.46
      2.43), total lean mass (OR=2.09, 95% CI=1.60-2.73) and appendicular lean mass
      (OR=1.57, 95% CI=1.27-1.95) and lower odds of 5% or more gain in total fat mass
      (OR=0.56, 95% CI=0.45-0.68) and truncal fat mass (OR=0.52, 95% CI=0.42-0.64) than
      those in the lowest quartile. These findings remained significant after
      accounting for age, site, baseline weight, physical activity, and change in
      physical activity. These associations were also independent of other metabolic
      syndrome features and medications. CONCLUSION: Greater lean mass loss and lower
      fat mass gain occurred in insulin-resistant men without diabetes mellitus than in
      insulin-sensitive men. Insulin resistance may accelerate age-related sarcopenia.

PMID- 21718264
TI  - Systematic review and meta-analysis: do clinical trials testing antimuscarinic
      agents for overactive bladder adequately measure central nervous system adverse
      events?
AB  - Experimental studies in healthy volunteers suggest that some antimuscarinic
      agents confer a risk of cognitive impairment, yet clinical trials of people with
      overactive bladder report only rare central nervous system (CNS) side effects. A
      lack of systematic measurement and reporting of CNS outcomes in clinical trials
      may partially explain this discrepancy. The purpose of this review and meta
      analysis was to ascertain the reporting bias associated with adverse CNS events
      in clinical drug trials of younger and older adults with overactive bladder.
      Articles were identified from MEDLINE and EMBASE databases until 2010 using the
      search terms "clinical trial" AND (one of) "oxybutynin, tolterodine,
      fesoterodine, propiverine, solifenacin, darifenacin, and trospium." Eligibility
      criteria included original randomized trials involving adults with overactive
      bladder; standard doses of medication; reports of confusion, somnolence,
      sedation, dizziness, drowsiness, asthenia, insomnia, and vertigo; no evidence of
      dementia at baseline; and trials in English. Seventy-seven percent (242/314) of
      eligible trials identified in the search neither measured nor reported CNS
      outcomes. Of the remaining 23%, it was difficult to distinguish whether CNS
      adverse events were systematically measured or spontaneously reported. Only one
      of 72 trials that were retained objectively measured changes in cognitive
      performance (Mini-Mental State Examination). Dizziness was the most frequently
      reported side effect, in 3% of oxybutynin, 3.2% of propiverine, and 1.8% of
      tolterodine users, compared with 1.6% with placebo. Confusion was reported in
      fewer than 1% of cases. Age-stratified analyses of CNS outcomes from trials in
      adults aged 65 and older with overactive bladder were found in only eight
      publications. Meta-analyses were conducted with 33 randomized, double-blind,
      placebo-controlled trials to determine the effect of each drug and dose on
      different CNS outcomes. Study heterogeneity, dosing inconsistency, and reporting
      bias limited interpretation of the findings from the meta-analyses. More-detailed
      standardized measurement of age-stratified CNS outcomes in clinical trials is
      required to better inform patients and clinicians about CNS risks associated with
      antimuscarinic agents.

PMID- 21718265
TI  - Sustained economic benefits of resistance training in community-dwelling senior
      women.
AB  - To determine whether the health and cost benefits of resistance training were
      sustained 12 months after formal cessation of the intervention. DESIGN: Cost
      utility analysis conducted alongside a randomized controlled trial. SETTING:
      Community-dwelling women aged 65 to 75 living in Vancouver, British Columbia.
      PARTICIPANTS: One hundred twenty-three of the 155 community-dwelling women aged
      65 to 75 years who originally were randomly allocated to once-weekly resistance
      training (n=54), twice-weekly resistance training (n=52), or twice-weekly balance
      and tone exercises (control group; n=49) participated in the 12-month follow-up
      study. Of these, 98 took part in the economic evaluation (twice-weekly balance
      and tone exercises, n=28; once-weekly resistance training, n=35; twice-weekly
      resistance training, n=35). MEASUREMENTS: The primary outcome measure was
      incremental cost per quality-adjusted life year (QALY) gained. Healthcare
      resource utilization was assessed over 21 months (2009 prices); health status was
      assessed using the EuroQol-5D to calculate QALYs using a 21-month time horizon.
      RESULTS: Once- and twice-weekly resistance training were less costly than balance
      and tone classes, with incremental mean healthcare costs of Canadian dollars
      (CAD$)1,857 and CAD$1,077, respectively. The incremental QALYs for once- and
      twice-weekly resistance training were -0.051 and -0.081, respectively, compared
      with balance and tone exercises. CONCLUSION: The cost benefits of participating
      in a 12-month resistance training intervention were sustained for the once- and
      twice-weekly resistance training group, whereas the health benefits were not.

PMID- 21718267
TI  - Risk of cerebrovascular accident associated with use of antipsychotics:
      population-based case-control study.
AB  - OBJECTIVES: To explore the association between use of antipsychotics and risk of
      cerebrovascular accident (CVA) in individuals with dementia aged 65 and older.
      DESIGN: Population-based case-control study. SETTING: UK-based electronic primary
      care records in the General Practice Research Database (GPRD). PARTICIPANTS:
      Individuals with dementia aged 65 and older registered in the database between
      January 1, 1995, and June 22, 2007. MEASUREMENTS: Odds ratio (OR) of CVA in users
      versus nonusers of antipsychotics (typical or atypical) and in users of typical
      versus atypical antipsychotics. Multivariate analyses were performed using
      logistic regression models to adjust for potential confounders: demographic
      variables, comorbidity, and concomitant treatments. RESULTS: After adjusting for
      confounding variables, the OR of CVA associated with use of only typical
      antipsychotics versus no antipsychotics in individuals with dementia aged 65 and
      older was 1.16 (95% confidence interval (CI)=1.07-1.27) and for use of only
      atypical antipsychotics versus no antipsychotics was 0.62 (95% CI=0.53-0.72). In
      the comparison of typical versus atypical antipsychotics, the OR was 1.83 (95%
      CI=1.57-2.14). CONCLUSION: No reasons were found to question the cerebrovascular
      safety of atypical antipsychotics in older adults with dementia. The typical
      antipsychotics appear to be associated with a higher risk of CVA, although the
      risk disappears after use is discontinued.

PMID- 21718266
TI  - Transient versus persistent fear of falling in community-dwelling older adults:
      incidence and risk factors.
AB  - OBJECTIVES: To investigate the incidence of fear of falling (FOF) and the risk
      factors associated with transient versus persistent FOF in community-dwelling
      older adults. DESIGN: Prospective cohort study. SETTING: Bronx County, New York.
      PARTICIPANTS: Three hundred eighty participants without FOF at baseline in the
      Einstein Aging Study aged 70 and older. MEASUREMENTS: FOF was assessed at
      baseline and during follow-up interviews at 2- to 3-month intervals for a minimum
      2 years. Incident FOF was classified as transient or persistent FOF. Transient
      FOF was defined as new-onset FOF reported at only one interview, and persistent
      FOF was FOF reported at two or more interviews over a 2-year period. RESULTS:
      Twenty-four-month cumulative incidence of incident FOF was 45.4%, with 60.0% of
      FOF being persistent. Predictors of incident FOF included female sex (adjusted
      hazard ratio (aHR)=1.55, 95% confidence interval (CI)=1.08-2.23), depressive
      symptoms (aHR=1.16, 95% CI=1.07-1.26), falls (aHR=1.50, 95% CI=1.01-2.21), and
      clinical gait abnormality (aHR=2.07, 95% CI=1.42-3.01). The proportion of
      participants with incident FOF increased linearly with increasing number of risk
      factors. Predictors for transient and persistent FOF were depressive symptoms and
      clinical gait abnormality. Female sex and previous falls were predictors of
      persistent but not transient FOF. CONCLUSION: FOF status in older adults may
      change over time, with shared and distinct risk factors for persistent and
      transient FOF. Understanding the dynamic nature of FOF and these risk factors
      will help identify high-risk groups and design future intervention studies.

PMID- 21718268
TI  - Cerebrospinal fluid beta-amyloid and tau are not associated with risk of
      delirium: a prospective cohort study in older adults with hip fracture.
AB  - OBJECTIVES: To examine the association between cerebrospinal fluid (CSF) beta
      amyloid (Abeta1-42), tau, and hyperphosphorylated tau (Ptau) and risk of delirium
      in older adults with hip fracture. DESIGN: Prospective cohort study. SETTING:
      University-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS:
      Seventy-six participants aged 75 and older admitted for surgical repair of acute
      hip fracture. MEASUREMENTS: Presurgical baseline screening and assessment
      included the Informant Questionnaire on Cognitive Decline-short form (IQCODE-N),
      Mini-Mental State Examination, standardized Snellen test for visual impairment,
      Geriatric Depression Scale, Barthel Index (BI), and Lawton Instrumental Activity
      of Daily Living (IADL) scale. The number of medical comorbidities and medications
      at home, American Society of Anesthesiologists score, and Acute Physiology and
      Chronic Health Evaluation II score were determined according to chart review.
      Delirium was diagnosed using the Confusion Assessment Method. CSF was collected
      at the onset of spinal anesthesia. RESULTS: Postoperative delirium occurred in 30
      (39.5%) participants. Participants with delirium were older, showed more signs of
      cognitive decline, were more dependent at home in activity of daily living and
      IADL functioning, and used more medications before admission. Preoperative CSF
      Abeta1-42, tau, and Ptau levels were not significantly different in participants
      who did and did not develop delirium during subsequent hospitalization. In
      contrast, prefracture cognitive decline (IQCODE-N) was significantly related to
      delirium (odds ratio=9.43, 95% confidence interval=2.45-36.31). CONCLUSION:
      Cognitive impairment predisposes to delirium, but in this study, postoperative
      delirium was not associated with baseline CSF Abeta1-42, tau, and Ptau levels.
      These findings suggest that CSF markers for plaque and tangle formation are not
      strongly associated with delirium risk in older adults with hip fracture.

PMID- 21718269
TI  - Vulnerability of older Latino and Asian immigrants with limited English
      proficiency.
AB  - OBJECTIVES: To explore the implications of limited English proficiency (LEP) for
      disparities in health status and healthcare service use of older Latino and Asian
      immigrants. DESIGN: Cross-sectional analysis of existing secondary data. SETTING:
      The 2007 California Health Interview Survey. PARTICIPANTS: Latino and Asian
      immigrants aged 60 and older (n=1,745) were divided into three language
      proficiency groups: older adults who have LEP, are proficient in English but also
      speak another language at home (EP), and speak English only (EO). MEASUREMENTS:
      Sociodemographic characteristics, health status, health service use, and barriers
      to service use were compared. RESULTS: Older Latino and Asian immigrants with LEP
      tended to have poorer self-rated health and higher psychological distress than
      the EP and EO groups. They were also less likely than the EP and EO groups to use
      health services and more likely to experience barriers to service use (e.g.,
      difficulty understanding written information at the doctor's office). CONCLUSION:
      Older Latinos and Asians with LEP are at higher risk for poor physical and mental
      health outcomes and inadequate health care. Healthcare systems should consider
      strategies to address the language needs of older immigrants to reduce the effect
      of linguistic disparities on access to care and ultimately to improve health
      status for these vulnerable populations.

PMID- 21718270
TI  - Effect of a high-intensity functional exercise program on functional balance:
      preplanned subgroup analyses of a randomized controlled trial in residential care
      facilities.
AB  - OBJECTIVES: To evaluate whether age, sex, depression, dementia disorder,
      nutritional status, or level of functional balance capacity influences the effect
      of a high-intensity functional weight-bearing exercise program on functional
      balance. DESIGN: Preplanned subgroup analyses of a randomized controlled trial.
      SETTING: Nine residential care facilities. PARTICIPANTS: One hundred ninety-one
      people aged 65 to 100 dependent in activities of daily living and with Mini
      Mental State Examination scores of 10 or greater. INTERVENTION: A high-intensity
      functional weight-bearing exercise program or a control activity, each comprising
      29 sessions over 3 months. MEASUREMENTS: Functional balance capacity was assessed
      blindly using the Berg Balance Scale (BBS) at baseline, 3 months, and 6 months.
      The BBS consists of 14 tasks, common in everyday life, such as standing up from
      sitting and, while standing, reaching forward or turning 360 degrees .
      Interactions between allocation to activity group and each subgroup were
      evaluated according to the intention-to-treat principle. RESULTS: The subgroup
      analyses revealed no statistically significant interaction for age, sex,
      depression, dementia disorder, nutritional status, or level of functional balance
      capacity at 3 (P=.65, .65, .51, .78, .09, .67, respectively) or 6 (P=.69, .62,
      .20, .94, .48, .85, respectively) months. In addition, at 3 and 6 months there
      was no significant interaction for cognitive level (P=.28, .47, respectively) or
      number of depressive symptoms (P=.85, .49, respectively). CONCLUSION: Older age,
      female sex, depression, mild to moderate dementia syndrome, malnutrition, and
      severe physical impairment do not seem to have a negative effect on functional
      balance from a high-intensity functional weight-bearing exercise program.
      Consequently, people with these characteristics in residential care facilities
      should not be excluded from offers of rehabilitation including high-intensity
      exercises.

PMID- 21718271
TI  - Holter monitoring in syncope: diagnostic yield in octogenarians.
AB  - OBJECTIVES: To determine the diagnostic yield of Holter monitoring in very old
      adults (>=80) with syncope. DESIGN: A Holter study was considered diagnostic if
      the arrhythmia explained syncope (atrioventricular (AV) block, sinus node
      dysfunction, atrial fibrillation with severe bradycardia or tachycardia,
      supraventricular or ventricular tachycardia). SETTING: A tertiary care center in
      Switzerland over a period of 10 years. PARTICIPANTS: Four hundred seventy-five
      Holter studies were performed in individuals aged 80 and older (median age 84,
      65% female, mean left ventricular ejection fraction (LVEF) 0.56 +/- 0.1%).
      MEASUREMENTS AND RESULTS: Fifty-three Holter studies (11%) were diagnostic. The
      detected arrhythmias were AV block (n=13), sinus node dysfunction (n=13), binodal
      disease (n=2), atrial fibrillation with slow or rapid ventricular response
      (n=21), ventricular tachycardia (n=3) and supraventricular tachycardia (n=1).
      Forty participants (8%) received a pacemaker, and one received an implantable
      cardioverter-defibrillator because of the results of Holter monitoring. The yield
      of Holter monitoring was significantly greater (all P<.01) in the presence of
      heart disease (17%) and low LVEF (22%), in men (17%) and in participants aged 90
      and older (20%). Heart disease (odds ratio (OR)=3.2, 95% confidence interval
      (CI)=1.7-6.1), male sex (OR=2.1, 95% CI=1.1-3.8), and aged 90 and older (OR=2.4,
      95% CI=1.2-5.1) remained independent predictors for a high diagnostic yield of
      Holter monitoring. Furthermore, Holter monitoring was helpful in excluding
      arrhythmias as a cause of syncope in an additional 10% of cases. CONCLUSION: The
      diagnostic value of Holter monitoring in participants aged 80 and older with
      syncope was 11.2%. Its yield was higher in men and in the presence of structural
      heart disease and was 20% in individuals aged 90 and older.

PMID- 21718272
TI  - Forced expiratory volume in 1 second and cognitive aging in men.
AB  - OBJECTIVES: To evaluate forced expiratory volume in 1 second (FEV(1) , a measure
      of overall lung function), long-term average FEV(1) , and rate of decline in
      FEV(1) in relation to cognition and cognitive decline in older men. DESIGN:
      Prospective observational study. SETTING: Community-based population.
      PARTICIPANTS: Eight hundred sixty-four older men from the Normative Aging Study.
      MEASUREMENTS: Starting in 1984, participants underwent triennial clinical
      evaluations. Lung function assessments provided estimates of FEV(1) . Cognitive
      assessments entailing tests of several cognitive abilities began in 1993. FEV(1)
      measured approximately 12 years before baseline cognitive testing, average FEV(1)
      over the 12-year period, and rate of change in FEV(1) were all evaluated in
      relation to baseline and change in performance on the cognitive tests. RESULTS:
      In multivariable-adjusted analyses, associations between FEV(1) and baseline
      cognitive scores were mixed, although average FEV(1) predicted significantly
      better performance on tests of visuospatial ability (P=.04) and general cognition
      (P=.03). Higher FEV(1) was more consistently associated with slower cognitive
      decline, but only the association between historical FEV(1) and attention was
      significant (difference per standard deviation in FEV(1) =0.056, P=.05). Rate of
      FEV(1) decline was not consistently associated with cognitive function or
      decline. Findings were generally similar or stronger in men who had never smoked.
      To account for potential bias due to selective attrition, inverse probability of
      censoring weights were applied to the cognitive decline analyses, yielding
      slightly larger estimates; the inadequate prognostic power of the censoring
      models limited this approach. CONCLUSION: Overall, the data provide limited
      evidence of an inverse association between FEV(1) and cognitive aging.

PMID- 21718273
TI  - Effect of an inpatient geriatric consultation team on functional outcome,
      mortality, institutionalization, and readmission rate in older adults with hip
      fracture: a controlled trial.
AB  - OBJECTIVES: To evaluate the effect of an inpatient geriatric consultation team
      (IGCT) on end points of interest in people with hip fracture: length of stay,
      functional status, mortality, new nursing home admission, and hospital
      readmission. DESIGN: Controlled trial based on assignment by convenience.
      SETTING: Trauma ward in a university hospital. PARTICIPANTS: One hundred seventy
      one people with hip fracture aged 65 and older. INTERVENTION: Participants were
      assigned to a multidisciplinary geriatric intervention (n=94) or usual care
      (n=77) during hospitalization after hip fracture. MEASUREMENTS: End points were
      functional status, length of stay, mortality, new nursing home admission, and
      hospital readmission 6 weeks, 4 months, and 12 months after surgery. RESULTS:
      Mean length of stay was 11.1 +/- 5.1 days in the intervention group and 12.4 +/-
      8.5 days in the control groups (P=.24). Complete adherence to IGCT
      recommendations was 56.8%. A significant benefit of intervention on functional
      status in univariate analyses (P=.02) 8 days after surgery disappeared in a
      linear mixed model. Participants with dementia had better functional status in a
      linear mixed model than those without (P=.03), but this effect was no longer
      significant after Bonferroni correction for multiple testing. After 6 weeks, 4
      months, and 12 months, no between-group differences could be documented for
      mortality, new nursing home admission, or readmission rate. CONCLUSION: This
      trial could not document functional benefits of an IGCT intervention in people
      with hip fracture. More research is needed to investigate whether a more
      intensive approach with more-direct control over patient management, more
      specific recommendations, and more-intense education would be effective.

PMID- 21718274
TI  - White matter lesions on brain magnetic resonance imaging scan and 5-year
      cognitive decline: the Honolulu-Asia aging study.
AB  - OBJECTIVES: To study white matter lesions (WMLs) and 5-year cognitive decline in
      elderly Japanese-American men. DESIGN: Longitudinal cohort study. SETTING:
      Population-based study in Honolulu, Hawaii. PARTICIPANTS: Japanese-American men
      aged 74 to 95 from the Honolulu-Asia Aging Study (HAAS) who were free of
      prevalent dementia, underwent a protocol brain MRI scan at the fifth HAAS
      examination (1994-1996), and returned for cognitive testing 5 years later
      (N=267). MEASUREMENTS: WMLs were dichotomized as present (grade 3-9, 38.2%) or
      absent (grade 1-2, 61.8%). Cognitive function was measured using the Cognitive
      Abilities Screening Instrument (CASI), and 5-year cognitive decline was defined
      as a drop in CASI score of 12 points or more (1 standard deviation). RESULTS: Men
      with WMLs on MRI at baseline were significantly more likely to experience
      cognitive decline at 5 years than those without (22.4% vs 34.4%, P=.03). Using
      multiple logistic regression, adjusting for age, education, apolipoprotein
      (Apo)E4 allele, large or small infarcts on MRI, baseline CASI score, and
      hypertension, those with WMLs were significantly more likely to develop 5-year
      cognitive decline (odds ratio=2.00, 95% confidence interval=1.10-3.65, P=.02).
      This association was stronger in men who were cognitively intact and free of the
      ApoE4 genotype and clinical stroke at baseline. CONCLUSION: Presence of WMLs on
      MRI was significantly associated with higher odds of 5-year cognitive decline in
      older Japanese-American men. Presence of WMLs may help identify people at risk
      for developing dementia, who may benefit from early intervention.

PMID- 21718275
TI  - Prevalence and effect on health-related quality of life of overactive bladder in
      older americans: results from the epidemiology of lower urinary tract symptoms
      study.
AB  - OBJECTIVE: To evaluate the prevalence and effect of overactive bladder (OAB) on
      healthcare-seeking behavior, mental health, and generic and condition-specific
      health-related quality of life (HRQL) in older adults. DESIGN: Secondary analysis
      of the U.S. sample of the Epidemiology of Lower Urinary Tract Symptoms (EpiLUTS)
      study-a population-based, cross-sectional, Internet-based survey. SETTING:
      Community. PARTICIPANTS: Two thousand four hundred eighty-five men and 2,877
      women aged 65 and older. MEASUREMENTS: Prevalence and effect on HRQL of urinary
      symptoms, including OAB. OAB was defined as the presence of urinary urgency
      and/or urinary urgency incontinence. Descriptive analyses and subgroup
      comparisons were conducted to evaluate the prevalence of OAB in men and women
      aged 65 and older and the effect of OAB on various aspects of HRQL. RESULTS: The
      survey response rate was 46.9% of men and 61.0% of women. Prevalence rates of OAB
      at least "sometimes" were 40.4% in men and 46.9% in women. OAB was associated
      with significant impairments across all domains of patient-reported outcomes,
      including general HRQL (Medical Outcomes Study 12-item Short-Form Survey),
      ratings of anxiety and depression (Hospital Anxiety and Depression Scale), and
      urinary condition-specific outcomes (Overactive Bladder Questionnaire Short Form
      and Patient Perception of Bladder Condition) (P<.001). CONCLUSION: OAB is common
      in older adults in the United States and is associated with substantial
      impairment in mental health and HRQL, but rates of treatment seeking behavior are
      low. Older patients should be assessed for OAB.

PMID- 21718276
TI  - The vulnerable elders survey-13 predicts hospital complications and mortality in
      older adults with traumatic injury: a pilot study.
AB  - OBJECTIVES: To determine whether the Vulnerable Elders Survey (VES)-13, a survey
      based on functional status that has been validated in uninjured older
      populations, will predict complications and mortality in injured older adults.
      DESIGN: Prospective observational pilot study. SETTING: Level 1 trauma center.
      PARTICIPANTS: Sixty-three older adults (>=65) with a traumatic injury who
      survived and required inpatient care for at least 24 hours. MEASUREMENTS: 
      PREDICTOR: preinjury VES-13 score (0-10 points, higher=greater risk) obtained by
      interviewing participants or proxies. OUTCOMES: composite outcome of one or more
      medical complications (e.g., aspiration pneumonia, respiratory failure) or death,
      discharge destination (home, nursing home, death), length of stay, hospital
      charges. Covariates: Charlson Comorbidity Index (CCI), Injury Severity Score
      (ISS), and sex. RESULTS: Of the 63 participants, 30 (48%) were discharged to home
      and 28 (44%) to a nursing facility, 21 (33%) developed one or more complications,
      and four (6%) died. In a model that also controlled for ISS and comorbidity, each
      additional VES-13 point was associated with greater risk of complication or death
      (odds ratio=1.53 per point, 95% confidence interval=1.12-2.07). CONCLUSION: The
      VES-13, in combination with injury severity, may be useful early in the hospital
      course to predict complications and death in older adults with traumatic injury,
      potentially identifying candidates who may benefit from additional inpatient
      geriatric services.

PMID- 21718277
TI  - Cognitive impairment predicts fatal incident stroke: findings from a national
      sample of older adults.
AB  - OBJECTIVES: To investigate the effect of cognitive impairment on fatal and
      nonfatal incident stroke in older adults. DESIGN: A large, national, prospective,
      population-based study of a representative cohort of older Canadians followed
      over a 10-year period. SETTING: Secondary analyses were conducted using data from
      the Canadian Study of Health and Aging, a population-based study of older adults
      followed prospectively from 1991 to 2001. PARTICIPANTS: Nine thousand four
      hundred fifty-one adults aged 65 and older who had not previously been diagnosed
      with stroke at baseline (in 1991). MEASUREMENTS: In addition to known risk
      factors, the independent contribution of cognitive function (diagnosed in a
      clinical examination) was examined as a risk for stroke in older adults. RESULTS:
      Multinomial logistic regression analyses showed that cognitive impairment was
      associated with twice the odds of fatal incident stroke, controlling for well
      established risk factors. CONCLUSION: This study provides further evidence for
      the need to consider cognitive function in relation to stroke risk in older
      populations.

PMID- 21718278
TI  - Functional analysis of splice site mutations in the human hairless (HR) gene
      using a minigene assay.
AB  - BACKGROUND: Congenital atrichia is a rare autosomal recessive form of isolated
      alopecia which is caused by mutations in the human hairless (HR) gene. Patients
      are born with normal hair that is shed almost completely and irreversibly during
      the first weeks of life. OBJECTIVES: To investigate the molecular genetic basis
      of congenital atrichia in two patients, and to analyse the functional
      consequences of one newly identified and all seven previously identified HR
      splice site mutations using a minigene assay. METHODS: Molecular analysis of the
      HR gene was performed by direct DNA sequencing. To analyse the functional
      consequences of the splice site mutations, the respective sequences were cloned
      into a vector which allows directed splicing. After transfection of COS7 cells,
      isolation of RNA and cDNA synthesis, sequencing was performed to analyse the
      products. RESULTS: Two novel mutations were identified: an insertion in exon 2
      (c.485insT; p.C162LfsX17), and a splice site mutation (c.2847-1G>A). In vitro
      analysis revealed aberrant splicing for all eight of the investigated HR splice
      site mutations. Comparison with the results of two biocomputational programs
      (neural network splice server and CRYP-SKIP) and calculation of consensus values
      revealed that the predictions of these two programs were consistent in only five
      and two of the eight mutations, respectively. CONCLUSIONS: This is the first
      report to analyse the consequences of HR splice site mutations using a cell-based
      in vitro assay. The results highlight the importance of performing splicing
      experiments to clarify the consequences of putative splice site mutations.

PMID- 21718279
TI  - Cytoskeletal and membrane remodelling during malaria parasite invasion of the
      human erythrocyte.
AB  - Erythrocytes are remarkably dynamic structures, possessing multiple and complex
      pathways for regulating cell membrane properties to compensate for the absence of
      a nucleus and internal membranes. Unlike the invasion strategies of many viruses
      and bacteria into their eukaryotic hosts, however, the accepted model for malaria
      parasite entry into human erythrocytes casts the host cell in a largely passive
      role. This is in contrast to mounting evidence for a suite of dynamic alterations
      that the erythrocyte membrane undergoes during the rapid process of invasion by
      the blood stage malaria parasite - the merozoite. Here we review the cellular and
      molecular basis for merozoite invasion of the erythrocyte and explore the idea
      that radical changes in the erythrocyte membrane protein and lipid architecture
      probably accompany this key step in the establishment of human malaria disease. 

PMID- 21718280
TI  - Diagnosis of Burkitt lymphoma using an algorithmic approach--applicable in both
      resource-poor and resource-rich countries.
AB  - Distinguishing Burkitt lymphoma (BL) from B cell lymphoma, unclassifiable with
      features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL
      (DLBCL/BL), and DLBCL is challenging. We propose an immunohistochemistry and
      fluorescent in situ hybridization (FISH) based scoring system that is employed in
      three phases - Phase 1 (morphology with CD10 and BCL2 immunostains), Phase 2
      (CD38, CD44 and Ki-67 immunostains) and Phase 3 (FISH on paraffin sections for
      MYC, BCL2, BCL6 and immunoglobulin family genes). The system was evaluated on 252
      aggressive B-cell lymphomas from Europe and from sub-Saharan Africa. Using the
      algorithm, we determined a specific diagnosis of BL or not-BL in 82%, 92% and 95%
      cases at Phases 1, 2 and 3, respectively. In 3.4% cases, the algorithm was not
      completely applicable due to technical reasons. Overall, this approach led to a
      specific diagnosis of BL in 122 cases and to a specific diagnosis of either DLBCL
      or DLBCL/BL in 94% of cases that were not diagnosed as BL. We also evaluated the
      scoring system on 27 cases of BL confirmed on gene expression/microRNA expression
      profiling. Phase 1 of our scoring system led to a diagnosis of BL in 100% of
      these cases.

PMID- 21718281
TI  - Statins therapy: a review on conventional and novel formulation approaches.
AB  - BACKGROUND AND OBJECTIVE: High levels of cholesterol lead to atherosclerosis, a
      factor predisposing to the development of coronary artery disease. Statin drugs,
      i.e. HMG-CoA reductase inhibitors, have been known since the end of the last
      century for their benefits against cardio- and cerebrovascular diseases and are
      widely used clinically. This review aims at compiling the research inputs being
      made for developing therapeutically efficacious dosage forms that have the
      potential to surmount the limitations of conventional dosage forms of statins.
      KEY FINDINGS: Statin drugs can reduce the endogenous synthesis of cholesterol and
      prevent the onset and development of atherosclerosis, and are therefore used as
      an effective treatment against primary hypercholesterolemia. At present, statin
      drugs are most often administered orally, on a daily basis. After administration,
      the bioavailability and the general circulation of statin drugs is fairly low due
      to the first-pass metabolism in the liver and clearance by the digestive system.
      Extensive pharmaceutical research in understanding the causes of low oral
      bioavailability has led to the development of novel technologies to address these
      challenges. SUMMARY: These technologies vary from conventional dosage forms to
      nanoparticulate drug-delivery systems, and have the potential to cause
      improvements in bioavailability and consequently therapeutic efficacy.

PMID- 21718282
TI  - Bismuth-ethanedithiol incorporated in a liposome-loaded tobramycin formulation
      modulates the alginate levels in mucoid Pseudomonas aeruginosa.
AB  - OBJECTIVES: This study examined the antibacterial activity, alginate modulation,
      and deposition of a tobramycin bismuth-ethanedithiol (Tob-Bi) conventional (free)
      or vesicle-entrapped (lipo) formulation against two mucoid Pseudomonas aeruginosa
      clinical isolates. METHODS: The inhibitory, bactericidal and biofilm eradication
      concentrations (in presence or absence of alginate lyase) were determined. The
      modulation of alginate was assessed by the carbazole assay and fluorescent
      labelling of live alginate-producing biofilms by confocal microscopy. The
      deposition of the formulations was assessed using the immunogold-labelling
      technique, transmission electron microscopy, and energy dispersive X-ray
      spectroscopy (EDS). KEY FINDINGS: The inhibitory and bactericidal concentrations
      for lipo Tob-Bi compared with free Tob-Bi were reduced in all strains by 2- to 8
      fold, and 2- to 32-fold, respectively. The biofilm eradication concentrations for
      lipo Tob-Bi compared with free Tob-Bi were reduced by 4- to 32-fold in the mucoid
      strains. The addition of alginate lyase transiently enhanced eradication for one
      mucoid strain only. The alginate levels were attenuated by more than half, and
      free Tob-Bi fared better than lipo Tob-Bi determined by the carbazole assay.
      Under confocal microscopy, alginate lyase reduced alginate levels and detached
      mucoid biofilms. Free and lipo Tob-Bi did not detach the bacteria from the
      surface, but attenuated alginate levels. Tobramycin was detected by immunogold
      labelling inside the bacterium, but EDS did not detect bismuth deposits.
      CONCLUSIONS: These findings substantiate a role in which tobramycin, bismuth, and
      alginate lyase play in eradicating mucoid P. aeruginosa growth and modulate
      alginate levels.

PMID- 21718283
TI  - Application of hydrotropy to transdermal formulations: hydrotropic solubilization
      of polyol fatty acid monoesters in water and enhancement effect on skin
      permeation of 5-FU.
AB  - OBJECTIVES: A hydrotropic formulation containing a percutaneous enhancer was
      developed for the transdermal formulation of a water-soluble drug and the
      solubilizing mechanisms of a percutaneous enhancer in water by a hydrotropic
      agent were investigated. The enhancement effect was also compared with the
      hydrotropic formulation and the other formulations using ethanol, propylene
      glycol or mixed micelles. METHODS: Sodium salicylate (SA) and sodium benzoate
      (BA) were selected as hydrotropic agents, and polyol fatty acid ester (POFE) and
      5-fluorouracil (5-FU) were selected as a percutaneous enhancer and a water
      soluble drug, respectively. Near-infrared (NIR) spectrophotometric and 1H NMR
      spectroscopic studies were carried out to investigate the solubilizing
      mechanisms. The mean particle size in the hydrotropic formulation was measured.
      The in-vitro skin permeation of 5-FU and the accumulation in the skin of
      propylene glycol monocaprylate (PGMC), one of the monoesters of POFE, from the
      hydrotropic formulation or the other formulations were investigated by using
      Franz-type diffusion cell. KEY FINDINGS: The presence of SA and BA had a visible
      effect on the O-H stretching band of water in the NIR region. The surface tension
      of SA and BA aqueous solutions was found to decrease with an increase in SA or BA
      concentration. Although SA interacted with PGMC in the presence of water, it did
      not interact with PGMC in the absence of water. Mean particle size in a solution
      consisting of 5% (v/v) PGMC and 30% SA aqueous solution was approximately 14 nm.
      1H NMR spectroscopic studies indicated that the hydrotropic salts formed
      aggregates with which PGMC interacted from the outside. The hydrotropic
      formulation prepared in this study enhanced skin permeation of 5-FU when compared
      with the other formulations. CONCLUSIONS: SA and BA solubilized monoesters of
      POFE in water, and SA interacted with PGMC in water. The hydrotropic formulation
      prepared in this study significantly enhanced skin permeation of 5-FU compared
      with the other formulations. The results suggest that a hydrotropic formulation
      containing PGMC may be a useful transdermal formulation for water-soluble drugs.

PMID- 21718284
TI  - A novel method using confocal laser scanning microscopy for sensitive measurement
      of P-glycoprotein-mediated transport activity in Caco-2 cells.
AB  - OBJECTIVES: The aim of this study was to use time-lapse confocal laser scanning
      microscopy to establish a more sensitive and specific method for evaluating P
      glycoprotein activity in Caco-2 cells. METHODS: The change in the fluorescence of
      residual rhodamine 123 at the apical and central regions of Caco-2 cells was
      measured in the presence of digoxin or St John's wort by using time-lapse
      confocal laser scanning microscopy. The data were compared with measurements made
      using conventional techniques, a fluorescence microplate reader and a
      fluorescence microscope. KEY FINDINGS: The percentage decrease of rhodamine 123
      caused by 10 um digoxin or 0.1 ug/ml St John's wort was significantly larger in
      the apical region of the Caco-2 cell than in the central region or in the whole
      cell. The digoxin-induced inhibition in the apical region as measured by time
      lapse confocal laser scanning microscopy was greater than that measured in the
      whole cell by a microplate reader or a fluorescence microscope. CONCLUSIONS: The
      assay of residual rhodamine 123 in the apical region of Caco-2 cells by confocal
      laser scanning microscopy was more sensitive than the conventional methods using
      a microplate reader or fluorescence microscopy. It will be a valuable screening
      tool for studying both the inhibition and induction of P-glycoprotein activity.

PMID- 21718285
TI  - In-vitro permeability of poorly water soluble drugs in the phospholipid vesicle
      based permeation assay: the influence of nonionic surfactants.
AB  - OBJECTIVES: The aim of this study was to determine the influence of nonionic
      surfactants on drug permeability using the phospholipid vesicle-based permeation
      assay (PVPA), which excludes other than trans-membrane diffusion pathways.
      METHODS: Barrier integrity was monitored both by electrical resistance and
      permeability measurement of the hydrophilic marker calcein. Permeability of the
      model drugs ketoprofen and nadolol across the PVPA-barrier was measured by HPLC
      UV. Micelle association of the model drugs was determined using ultrafiltration,
      whereby micelle-bound drug and molecular drug were separated. KEY FINDINGS: The
      nonionic surfactant poloxamer 188 was demonstrated not to affect barrier
      integrity. Drug permeability was found depressed in the presence of poloxamer 188
      in a concentration-dependent manner. Both drugs were found to associate with
      poloxamer 188 micelles. The extent of the decrease in permeability correlated
      mostly, but not in all cases, with the fraction of micelle-bound drug.
      CONCLUSIONS: Micelle association was one important but not the only factor
      affecting drug permeability across the PVPA-barrier.

PMID- 21718286
TI  - A derivative of 2-aminothiazole inhibits melanogenesis in B16 mouse melanoma
      cells via glycogen synthase kinase 3beta phosphorylation.
AB  - OBJECTIVES: We have investigated whether KHG25855 (2-cyclohexylamino-1,3-thiazole
      hydrochloride) affected melanogenesis in B16 mouse melanoma cells, and the
      mechanisms involved. METHODS: Melanin content and tyrosinase activity were
      measured using an ELISA reader after cells were treated with KHG25855. KHG25855
      induced signalling pathways were examined using Western blot analysis. KEY
      FINDINGS: KHG25855 decreased melanin production in a dose-dependent fashion, but
      KHG25855 did not directly inhibit tyrosinase, the rate-limiting melanogenic
      enzyme. The expression of microphthalmia-associated transcription factor,
      tyrosinase, and the related signal transduction pathways were also investigated.
      The effects of KHG25855 on the extracellular signal-regulated kinase and cAMP
      response element binding protein signalling pathways were determined, and
      KHG25855 was shown to have no effect on these signalling pathways. The Wnt
      signalling pathway is also deeply involved in melanogenesis, and so glycogen
      synthase kinase 3beta (GSK3beta) phosphorylation was assessed after KHG25855
      treatment; KHG25855 caused GSK3beta phosphorylation (inactivation), but the level
      of beta-catenin was not changed by KHG25855. Furthermore, alpha-melanocyte
      stimulating hormone-induced tyrosinase expression was downregulated by KHG25855.
      CONCLUSIONS: We propose that KHG25855 showed hypopigmentary activity through
      tyrosinase downregulation via GSK3beta phosphorylation.

PMID- 21718287
TI  - Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and
      spermidine/spermine N-1-acetyl-transferase gene expression induced by renal
      ischaemia-reperfusion in rats.
AB  - OBJECTIVES: Renal ischaemia-reperfusion (I/R) is a well-characterised model of
      acute renal failure that causes both local and remote organ injury. The aim of
      this work was to investigate the effect of thymoquinone, the main constituent of
      the volatile oil extracted from Nigella sativa seeds, on renal and hepatic
      changes after renal ischaemia-reperfusion. METHODS: Male Sprague-Dawley rats were
      divided into sham I/R vehicle-treated groups, and I/R thymoquinone-treated
      groups. Thymoquinone (10 mg/kg, p.o.) was administered for ten consecutive days
      to the I/R thymoquinone group before injury. I/R and I/R thymoquinone groups were
      subjected to 30-min ischaemia followed by 4-h reperfusion. KEY FINDINGS: I/R
      resulted in a significant increase in malondialdehyde (MDA) level and decreases
      in glutathione-S-transferase (GST) and superoxide dismutase (SOD) activity in
      liver and kidney tissues. Thymoquinone treatment caused the reversal of I/R
      induced changes in MDA as well as GST and SOD activity. Moreover, I/R caused a
      significant rise in creatinine and alanine aminotransferase serum levels. CYP3A1
      mRNA expression was induced significantly by I/R in both liver and kidney tissues
      compared with sham group. Thymoquinone reduced significantly this increase. I/R
      caused induction of mRNA expression of spermidine/spermine N-1-acetyl-transferase
      (SSAT), a catabolic enzyme that participates in polyamine metabolism, in liver
      and kidney tissues. Thymoquinone reduced SSAT mRNA expression significantly in
      liver and markedly in kidney. CONCLUSIONS: These findings suggested that
      thymoquinone protected against renal I/R-induced damage through an antioxidant
      mechanism as well as the decrease of CYP3A1 and SSAT gene expression.

PMID- 21718288
TI  - Impact of fusion to Galpha(i2) and co-expression with RGS proteins on
      pharmacological properties of human cannabinoid receptors CB1R and CB2R.
AB  - OBJECTIVES: G protein coupled receptor (GPCR)-Galpha fusion proteins are often
      employed to investigate receptor/G protein interaction. In this study, the impact
      of Galpha fusion proteins on pharmacology of CBRs, both mediating signals through
      Galpha(i) proteins, were investigated. Galpha(i2) was fused to the C-terminus of
      the CBRs or co-expressed with non-fused Galpha(i2) in Sf9 cells, always together
      with Gbeta1gamma2. Furthermore, the impact of RGS proteins on CBR signaling in
      combination with the CBR fusion approach was examined, using RGS4 and RGS19 as
      paradigms. METHODS: CBR ligands were characterized in the steady-state GTPase
      assay and pharmacological properties of ligands in the different test systems
      were correlated. KEY FINDINGS: Fusion of CBRs to Galpha(i2) enhanced the maximal
      stimulatory effects of ligands compared to the co-expression system, especially
      for CB2R. RGS4, but not RGS19, behaved as a GTPase-activating protein at CBRs in
      the Galpha(i2) co-expression and fusion system. Fusion of GPCR, most prominently
      CB2R, to Galpha(i2) , and co-expression with RGS4 altered the pharmacological
      properties of ligands. CONCLUSIONS: Our data suggest that fusion of CB2R to
      Galpha(i2) and co-expression with RGS4 impedes with conformational changes.
      Moreover, our results support the concept of ligand-specific receptor
      conformations. Finally, this paper describes the most sensitive CBR test system
      currently available.

PMID- 21718289
TI  - Endothelium-independent vasorelaxation by ticlopidine and clopidogrel in rat
      caudal artery.
AB  - OBJECTIVES: Thienopyridines are prodrugs currently used as anti-aggregating
      agents. The aim of this study was to determine if these compounds might have
      vascular activity independent of hepatic bioactivation. METHODS: The direct
      activity of thienopyridines was studied in rat caudal arterial rings and aortic
      smooth muscle cells in culture. KEY FINDINGS: Both compounds (0.01 um-100 um)
      showed a concentration-dependent vasorelaxation in arterial tissues precontracted
      with phenylephrine, 5-hydroxytryptamine and KCl. The relaxation induced by 100 um
      ticlopidine and clopidogrel was greater than 80%. The relaxation by ticlopidine
      was compared with the activity of acetylcholine. These two agents showed similar
      potency, although ticlopidine was slightly more active. Pretreatment with the
      nitric oxide synthase inhibitor L-NAME inhibited the relaxation by acetylcholine
      but not that by ticlopidine. To further study vasorelaxation by ticlopidine,
      other pharmacological inhibitors including propranolol, nifedipine and suramin
      were used. These compounds lacked inhibitory effects on the vasorelaxation by
      ticlopidine. In vascular smooth muscle cells, 1 um ticlopidine induced a decrease
      in cell proliferation, while incubation with both ticlopidine and ADP or 2
      methioADP led to an additive effect. CONCLUSIONS: The data suggest that
      ticlopidine and clopidogrel cause relaxation of arterial tissues and influence
      vascular smooth muscle cell proliferation directly without hepatic
      biotransformation. Furthermore, the arterial relaxation induced in vitro by
      thienopyridines is endothelium independent, and beta-adrenergic and P2 receptors
      are not involved.

PMID- 21718290
TI  - Pre-emptive intrathecal quinidine alleviates spinal nerve ligation-induced
      peripheral neuropathic pain.
AB  - OBJECTIVES: Quinidine, a class I anti-arrhythmic agent, is a sodium channel
      blocker that is more potent than lidocaine and mexiletine. This study tested pre
      emptive intrathecal quinidine to attenuate neuropathic pain induced by lumbar
      spinal nerve ligation (SNL). METHODS: Ninety-six adult male Sprague-Dawley rats
      were grouped equally (n=24 per group) as follows: group S (sham), removal of
      transverse process only; group L, SNL; group Q35, SNL pretreated with intrathecal
      quinidine 35 mM (50 ul); group Q70, SNL pretreated with intrathecal quinidine 70
      mM (50 ul). Neuropathic pain was measured by thermal hyperalgesia and mechanical
      allodynia. Other measurements included dys-regulation of sodium channel Nav1.3 in
      dorsal root ganglion (DRG) and spinal microglia activation in spinal dorsal horn.
      KEY FINDINGS: Spinal nerve ligation induced abnormal mechanical allodynia and
      thermal hyperalgesia, up-regulated Nav1.3 in DRG, and activated microglia in
      spinal cord. Group Q70 showed attenuated thermal hyperalgesia (P<0.001) and
      mechanical allodynia (P<0.05) on postoperative day 5 (POD5) but not on POD7,
      reversed up-regulated expression of Nav1.3 on POD3 and POD7 in DRG and
      significantly attenuated microglia activation on POD7 (P=0.032) in spinal cord.
      CONCLUSIONS: Pretreatment with intrathecal quinidine 70 mM before SNL attenuates
      nerve ligation-induced neuropathic pain. The duration of the effect is 5 days.

PMID- 21718291
TI  - Anti-inflammatory, analgesic and antipyretic effects of friedelin isolated from
      Azima tetracantha Lam. in mouse and rat models.
AB  - OBJECTIVES: Friedelin was isolated from Azima tetracantha Lam. leaves collected
      from Kallakurichi, Villuppuram district, Tamil Nadu, India. The anti
      inflammatory, analgesic and antipyretic activities of friedelin have been
      investigated in Wistar rats and mice. METHODS: Friedelin was isolated from the
      hexane extract of leaves of A. tetracantha using column chromatography. The
      effects of friedelin on inflammation were studied by using carrageenan-induced
      hind paw oedema, croton oil-induced ear oedema, acetic acid-induced vascular
      permeability, cotton pellet-induced granuloma and adjuvant-induced arthritis. The
      analgesic effect of friedelin was evaluated using the acetic acid-induced
      abdominal constriction response, formalin-induced paw licking response and the
      hot-plate test. The antipyretic effect of friedelin was evaluated using the yeast
      induced hyperthermia test in rats. KEY FINDINGS: In the acute phase of
      inflammation, maximum inhibitions of 52.5 and 68.7% (P<0.05) were noted with 40
      mg/kg friedelin in carrageenan-induced paw oedema and croton oil-induced ear
      oedema, respectively. Administration of friedelin (40 mg/kg) significantly
      (P<0.05) decreased the formation of granuloma tissue induced by cotton pellet at
      a rate of 36.3%. In the adjuvant-induced arthritis test friedelin inhibited 54.5%
      of paw thickness. Friedelin inhibited acetic acid-induced vascular permeability
      in mice. Friedelin also produced significant (P<0.05) analgesic activity in the
      acetic acid-induced abdominal constriction response and formalin-induced paw
      licking response. In the hot-plate test, friedelin did not show any significant
      results when compared with control. Treatment with friedelin showed a significant
      (P<0.05) dose-dependent reduction in pyrexia in rats. CONCLUSIONS: The results
      suggested that friedelin possessed potent anti-inflammatory, analgesic and
      antipyretic activities.

PMID- 21718292
TI  - Cytotoxic evaluation and induction of mitochondria-mediated apoptosis in human
      leukaemia HL-60 cells by Carissa spinarum stem isolate.
AB  - OBJECTIVE: To evaluate Carissa spinarum stem isolate for its anti-cancer
      therapeutic potential. METHODS: The n-butanol fraction of aqueous extract from
      Carissa spinarum stem was assessed for its cytotoxic and pro-apoptotic activity.
      KEY FINDINGS: We report for the first time the anti-cancer potential of C.
      spinarum stem aqueous extract (CSE) and its n-butanol fraction (CSF). Both
      inhibited cell proliferation of various human cancer cell lines in which
      leukaemia HL-60 cells treated with CSF showed maximum growth inhibition having an
      inhibitory concentration (IC(50) ) value of 34.58+/-0.91 ug/ml. In addition, CSF
      induced concentration-dependent apoptosis in HL-60 cells as measured by various
      end-points (e.g. Annexin V binding, DNA laddering, apoptotic body formation and
      an increase in hypodiploid subG0 DNA content). Moreover, persistent levels of
      reactive oxygen species caused translocation of Bax to mitochondria and Bcl-2
      degradation, which led to loss of mitochondrial membrane potential and release of
      cytochrome c to the cytosol. These events were associated with significant
      activation of caspase-3, caspase-6 and caspase-9 leading to poly (ADP-ribose)
      polymerase cleavage. CONCLUSION: All the above parameters revealed that CSF
      induced apoptosis through the mitochondrial dependent pathway in HL-60 cells.

PMID- 21718293
TI  - Esenbeckia leiocarpa Engl. inhibits inflammation in a carrageenan-induced murine
      model of pleurisy.
AB  - OBJECTIVES: The aim of this study was to investigate the anti-inflammatory
      effects of the crude hydroalcoholic extract (CHE) isolated from Esenbeckia
      leiocarpa Engl., and fractions and subfractions derived from it. METHODS: Dried
      E. leiocarpa Engl. bark was macerated and extracted with ethanol to obtain the
      CHE. The n-hexane, ethyl acetate, aqueous and alkaloid fractions, as well as two
      alkaloid subfractions (polar and nonpolar) were obtained from the CHE. A
      preliminary analysis using thin-layer chromatography was performed. Capillary
      electrophoresis, physical characteristics and spectral data produced by IR
      analysis and nuclear magnetic resonance (1H and 13C NMR), and mass spectrometry
      analysis were used to identify and elucidate the structure of the major
      compounds. Swiss mice were used in a carrageenan-induced pleurisy model. Pro
      inflammatory parameters (leukocyte and exudate concentrations, myeloperoxidase
      and adenosine-deaminase activity, and nitrate/nitrite, interleukin 1beta and
      tumour necrosis factor alpha levels) were quantified in exudates at 4 h after
      carrageenan-induced pleurisy in mice. KEY FINDINGS: The dihydrocorynantheol
      alkaloid was isolated as the majority compound in the CHE, ethyl acetate and
      alkaloid fractions, and in the polar and nonpolar alkaloid subfractions. The CHE,
      fractions and subfractions inhibited the increases in leukocyte and exudate
      concentrations, myeloperoxidase and adenosine-deaminase activity, and
      nitrite/nitrate, interleukin 1beta, and tumour necrosis factor alpha levels
      (P<0.05) in the fluid secreted from the pleural cavity of the carrageenan-treated
      mice. CONCLUSIONS: E. leiocarpa Engl. showed significant in vivo anti
      inflammatory action by inhibiting the inflammation caused by carrageenan. This
      effect may be, in part, due to the dihydrocorynantheol alkaloid, which was
      identified as the majority compound isolated from E. leiocarpa bark.

PMID- 21718294
TI  - Inhibition of ketamine-induced hyperlocomotion in mice by the essential oil of
      Alpinia zerumbet: possible involvement of an antioxidant effect.
AB  - OBJECTIVES: The antipsychotic, hypnotic, myorelaxant and antioxidant effects of
      the essential oil of Alpinia zerumbet (EOAZ) were studied. METHODS: EOAZ (50, 100
      and 200 mg/kg i.p.) was administered once to mice for the determination of
      antipsychotic activity (evaluated by ketamine-induced hyperlocomotion), hypnotic
      activity (induced by sodium pentobarbital, 40 mg/kg i.p.), motor coordination
      (rotarod test), antioxidant effects (determination of lipid peroxidation and GSH
      levels), as well as alterations in nitric oxide levels (determination of nitrite
      content). KEY FINDINGS: EOAZ at doses of 100 and 200 mg/kg prevented ketamine
      hyperlocomotion, as did haloperidol (0.2 mg/kg i.p). EOAZ at a dose of 200 mg/kg
      decreased sleep latency, while all doses increased sleeping time. There was no
      effect on motor coordination. The in-vitro antioxidant capacity of the oil caused
      a decrease in lipid peroxidation and increase in GSH levels. EOAZ also prevented
      the decrease in nitrite content caused by oxidative stress. CONCLUSIONS: The
      results suggest antipsychotic and antioxidant effects for the EOAZ that may have
      promising efficacy for the treatment of schizophrenia.

PMID- 21718295
TI  - Up-regulation of P-glycoprotein reduces intracellular accumulation of beta
      amyloid: investigation of P-glycoprotein as a novel therapeutic target for
      Alzheimer's disease.
AB  - OBJECTIVES: Several studies have suggested the efflux transporter P-glycoprotein
      (P-gp) to play a role in the etiology of Alzheimer's disease through the
      clearance of amyloid beta (Abeta) from the brain. In this study, we aimed to
      investigate the possibility of P-gp as a potential therapeutic target for
      Alzheimer's disease by examining the impact of P-gp up-regulation on the
      clearance of Abeta, a neuropathological hallmark of Alzheimer's disease. METHODS:
      Uptake studies for 125I-radiolabelled Abeta1-40, and fluorescent immunostaining
      technique for P-gp and fluorescent imaging of Abeta1-40 were carried out in LS
      180 cells following treatment with drugs known to induce P-gp expression. KEY
      FINDINGS: Approximately 10-35% decrease in 125I-Abeta1-40 intracellular
      accumulation was observed in cells treated with rifampicin, dexamethasone,
      caffeine, verapamil, hyperforin, beta-estradiol and pentylenetetrazole compared
      with control. Also, fluorescent micrographs showed an inverse relationship
      between levels of P-gp expression and 5-carboxyfluorescein labelled Abeta (FAM
      Abeta1-40) intracellular accumulation. Quantitative analysis of the micrographs
      revealed that the results were consistent with those of the uptake studies using
      125I-Abeta1-40. CONCLUSIONS: The investigated drugs were able to improve the
      efflux of Abeta1-40 from the cells via P-gp up-regulation compared with control.
      Our results elucidate the importance of targeting Abeta clearance via P-gp up
      regulation, which will be effective in slowing or halting the progression of
      Alzheimer's disease.

PMID- 21718296
TI  - Interactions between antidepressants and P-glycoprotein at the blood-brain
      barrier: clinical significance of in vitro and in vivo findings.
AB  - The drug efflux pump P-glycoprotein (P-gp) plays an important role in the
      function of the blood-brain barrier by selectively extruding certain endogenous
      and exogenous molecules, thus limiting the ability of its substrates to reach the
      brain. Emerging evidence suggests that P-gp may restrict the uptake of several
      antidepressants into the brain, thus contributing to the poor success rate of
      current antidepressant therapies. Despite some inconsistency in the literature,
      clinical investigations of potential associations between functional single
      nucleotide polymorphisms in ABCB1, the gene which encodes P-gp, and
      antidepressant response have highlighted a potential link between P-gp function
      and treatment-resistant depression (TRD). Therefore, co-administration of P-gp
      inhibitors with antidepressants to patients who are refractory to antidepressant
      therapy may represent a novel therapeutic approach in the management of TRD.
      Furthermore, certain antidepressants inhibit P-gp in vitro, and it has been
      hypothesized that inhibition of P-gp by such antidepressant drugs may play a role
      in their therapeutic action. The present review summarizes the available in
      vitro, in vivo and clinical data pertaining to interactions between
      antidepressant drugs and P-gp, and discusses the potential relevance of these
      interactions in the treatment of depression.

PMID- 21718297
TI  - Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five
      screening models of pro-arrhythmia reveals lack of specificity of isolated
      cardiomyocytes.
AB  - BACKGROUND AND PURPOSE: Drug development requires the testing of new chemical
      entities for adverse effects. For cardiac safety screening, improved assays are
      urgently needed. Isolated adult cardiomyocytes (CM) and human embryonic stem cell
      derived cardiomyocytes (hESC-CM) could be used to identify pro-arrhythmic
      compounds. In the present study, five assays were employed to investigate their
      sensitivity and specificity for evaluating the pro-arrhythmic properties of I(Kr)
      blockers, using moxifloxacin (safe compound) and dofetilide or E-4031 (unsafe
      compounds). EXPERIMENTAL APPROACH: Assays included the anaesthetized remodelled
      chronic complete AV block (CAVB) dog, the anaesthetized methoxamine-sensitized
      unremodelled rabbit, multi-cellular hESC-CM clusters, isolated CM obtained from
      CAVB dogs and isolated CM obtained from the normal rabbit. Arrhythmic outcome was
      defined as Torsade de Pointes (TdP) in the animal models and early
      afterdepolarizations (EADs) in the cell models. KEY RESULTS: At clinically
      relevant concentrations (5-12 uM), moxifloxacin was free of pro-arrhythmic
      properties in all assays with the exception of the isolated CM, in which 10 uM
      induced EADs in 35% of the CAVB CM and in 23% of the rabbit CM. At supra
      therapeutic concentrations (>=100 uM), moxifloxacin was pro-arrhythmic in the
      isolated rabbit CM (33%), in the hESC-CM clusters (18%), and in the methoxamine
      rabbit (17%). Dofetilide and E-4031 induced EADs or TdP in all assays (50-83%),
      and the induction correlated with a significant increase in beat-to-beat
      variability of repolarization. CONCLUSION AND IMPLICATIONS: Isolated
      cardiomyocytes lack specificity to discriminate between TdP liability of the
      I(Kr) blocking drugs moxifloxacin and dofetilide or E4031.

PMID- 21718298
TI  - Okadaic acid induces matrix metalloproteinase-9 expression in fibroblasts:
      crosstalk between protein phosphatase inhibition and beta-adrenoceptor
      signalling.
AB  - BACKGROUND AND PURPOSE: Interactions between protein phosphatase inhibition and
      matrix metalloproteinase (MMP)-9 expression have implications for tissue
      remodelling after injury. Stimulation of beta-adrenoceptors could affect such
      interactions as isoprenaline increases protein phosphatase 2A (PP2A) activity and
      MMP-9 abundance. We investigated the effect of okadaic acid (OA) on MMP-9
      expression to assess interactions between phosphatase inhibition and beta
      adrenoceptor signalling in fibroblasts. EXPERIMENTAL APPROACH: Fibroblasts were
      exposed to OA alone and in combination with isoprenaline. Effects on MMP-9
      expression and intracellular signalling were studied using promoter assays,
      Western blot analysis and siRNA methodologies. KEY RESULTS: Okadaic acid
      increased MMP-9 abundance in human cardiac ventricular fibroblasts, NIH3T3
      fibroblasts and hepatic stellate cells. This effect was unaffected by PP2A
      knockdown in NIH3T3 cells. OA increased phosphorylation of NF-kappaB, but not NF
      kappaB promoter activity, IkappaBalpha degradation, or nuclear translocation of
      p65-NF-kappaB. Exposure to SB202190 (p38 MAPK), U0126 (ERK1/2) and NF-kappaB III
      inhibitor revealed that OA induced MMP-9 activity through p38 MAPK. Isoprenaline
      inhibited OA-mediated MMP-9 expression in NIH3T3, in a beta-arrestin 2- and PP2A
      dependent manner. Mutation of the activator protein-1 (AP-1) and NF-kappaB
      binding sites demonstrated that OA-induced MMP-9 activity was mediated through
      the AP-1 but not NF-kappaB sites. The latter mediated the inhibitory effect of
      isoprenaline on OA-induced MMP-9 promoter activity. CONCLUSION AND IMPLICATIONS:
      Okadaic acid induced MMP-9 activity through p38 MAPK and was inhibited by
      isoprenaline via a pathway involving beta-arrestin 2, PP2A and an NF-kappaB
      binding motif. These findings elucidate how phosphoprotein phosphatases and
      adrenoceptors may modulate tissue remodelling by affecting fibroblast function.

PMID- 21718299
TI  - Adiponectin receptor signalling in the brain.
AB  - Adiponectin is an important adipocyte-derived hormone that regulates metabolism
      of lipids and glucose, and its receptors (AdipoR1, AdipoR2, T-cadherin) appear to
      exert actions in peripheral tissues by activating the AMP-activated protein
      kinase, p38-MAPK, PPARalpha and NF-kappa B. Adiponectin has been shown to exert a
      wide range of biological functions that could elicit different effects, depending
      on the target organ and the biological milieu. There is substantial evidence to
      suggest that adiponectin receptors are expressed widely in the brain. Their
      expression has been detected in regions of the mouse hypothalamus, brainstem,
      cortical neurons and endothelial cells, as well as in whole brain and pituitary
      extracts. While there is now considerable evidence for the presence of
      adiponectin and its receptors in the brain, their precise roles in brain diseases
      still remain unclear. Only a few research studies have looked at this facet of
      adiponectins in brain disorders. This brief review will describe the evidence for
      important functions by adiponectin, its structure and known actions, evidence for
      expression of AdipoRs in the brain, their involvement in brain disorders and the
      therapeutic potential of agents that could modify AdipoR signalling.

PMID- 21718300
TI  - Molecular mechanisms underlying bile acid-stimulated glucagon-like peptide-1
      secretion.
AB  - BACKGROUND AND PURPOSE: The glucagon-like peptides GLP-1 and GLP-2 are secreted
      from enteroendocrine L-cells following nutrient ingestion. Drugs that increase
      activity of the GLP-1 axis are highly successful therapies for type 2 diabetes,
      and boosting L-cell secretion is a potential strategy for future diabetes
      treatment. The aim of the present study was to further our understanding of the
      bile acid receptor GPBA (TGR5), an L-cell target currently under therapeutic
      exploration. EXPERIMENTAL APPROACH: GLUTag cells and mixed primary murine
      intestinal cultures were exposed to bile acids and a specific agonist, GPBAR-A.
      Secretion was measured using hormone assays and intracellular calcium and cAMP
      responses were monitored using real-time imaging techniques. KEY RESULTS: Bile
      acid-triggered GLP-1 secretion from GLUTag cells was GPBA-dependent, as
      demonstrated by its abolition following tgr5 siRNA transfection. Bile acids and
      GPBAR-A increased GLP-1 secretion from intestinal cultures, with evidence for
      synergy between the effects of glucose and GPBA activation. Elevation of cAMP was
      observed following GPBA activation in individual GLUTag cells. Direct calcium
      responses to GPBAR-A were small, but in the presence of the agonist, a
      subpopulation of cells that was previously poorly glucose-responsive exhibited
      robust glucose responses. In vivo, increased delivery of bile to more distal
      regions of the ileum augmented L-cell stimulation. CONCLUSIONS AND IMPLICATIONS:
      GPBA signalling in L-cells involves rapid elevation of cAMP, and enhanced calcium
      and secretory responses to glucose. Modulation of this receptor therapeutically
      may be an attractive strategy to enhance GLP-1 secretion and achieve better
      glycaemic control in diabetic patients.

PMID- 21718301
TI  - The GPCR-associated sorting protein 1 regulates ligand-induced down-regulation of
      GPR55.
AB  - BACKGROUND AND PURPOSE: Many GPCRs, including the CB(1) cannabinoid receptor, are
      down-regulated following prolonged agonist exposure by interacting with the GPCR
      associated sorting protein-1 (GASP-1). The CB(1) receptor antagonist rimonabant
      has also recently been described to be an agonist at GPR55, a cannabinoid-related
      receptor. Here we investigated the post-endocytic properties of GPR55 after
      agonist exposure and tested whether GASP-1 is involved in this process.
      EXPERIMENTAL APPROACH: We evaluated the direct protein-protein interaction of
      GPR55 with GASP-1 using (i) GST-binding assays and (ii) co-immunoprecipitation
      assays in GPR55-HEK293 cells with endogenous GASP-1 expression. We further tested
      the internalization, recycling and degradation of GPR55 using confocal
      fluorescence microscopy and biotinylation assays in the presence and absence of
      GASP-1 (lentiviral small hairpin RNA knockdown of GASP-1) under prolonged agonist
      [rimonabant (RIM), lysophosphatidylinositol (LPI)] stimulation. KEY RESULTS: We
      showed that the prolonged activation of GPR55 with rimonabant or LPI down
      regulates GPR55 via GASP-1. GASP-1 binds to GPR55 in vitro, and this interaction
      was required for targeting GPR55 for degradation. Disrupting the GPR55-GASP-1
      interaction prevented post-endocytic receptor degradation, and thereby allowed
      receptor recycling. CONCLUSION AND IMPLICATIONS: These data implicate GASP-1 as
      an important regulator of ligand-mediated down-regulation of GPR55. By
      identifying GASP-1 as a key regulator of the trafficking and, by extension,
      functional expression of GPR55, we may be one step closer to gaining a better
      understanding of this receptor in response to cannabinoid drugs. LINKED ARTICLES:
      This article is part of a themed section on Cannabinoids in Biology and Medicine.
      To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in
      Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.

PMID- 21718302
TI  - Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and
      chronic opiate treatments.
AB  - BACKGROUND AND PURPOSE Opiates remain the most effective compounds for
      alleviating severe pain across a wide range of conditions. However, their use is
      associated with significant side effects. Neuropeptide FF (NPFF) receptors have
      been implicated in several opiate-induced neuroadaptive changes including the
      development of tolerance. In this study, we investigated the consequences of NPFF
      receptor blockade on acute and chronic stimulation of opioid receptors in mice by
      using RF9, a potent and selective antagonist of NPFF receptors that can be
      administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were
      investigated on opioid pharmacological responses including locomotor activity,
      antinociception, opioid-induced hyperalgesia, rewarding properties and physical
      dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal
      hyperlocomotion and slightly attenuated the decrease induced in vertical
      activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia
      produced by either acute fentanyl or chronic morphine administration. RF9 also
      potentiated opiate early analgesic effects and prevented the development of
      morphine tolerance. Finally, RF9 increased morphine-induced conditioned place
      preference without producing any rewarding effect by itself and decreased
      naltrexone-precipitated withdrawal syndrome following chronic morphine treatment.
      CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two
      major undesirable effects: tolerance and dependence, which are clinically
      associated with prolonged exposure to opiates. Our findings suggest that NPFF
      receptors are interesting therapeutic targets to improve the analgesic efficacy
      of opiates by limiting the development of tolerance, and for the treatment of
      opioid dependence.

PMID- 21718303
TI  - Novel insights into the delayed vasospasm following subarachnoid haemorrhage:
      importance of proteinase signalling.
AB  - This article summarizes the findings of Kameda et al. (this issue of BJP) that
      suggest a new avenue for the pharmacological treatment of subarachnoid
      haemorrhage (SAH) involving the combined use of a proteinase inhibitor
      (argatroban) that targets thrombin and an antioxidant (vitamin C). The findings
      are presented in the context of previous modalities of treating SAH that are of
      modest impact and the possibility that inhibiting proteinase-mediated signalling
      via proteinase-activated receptors like the thrombin PAR1 receptor combined with
      blocking oxidative stress may provide a new avenue for the treatment of SAH.

PMID- 21718304
TI  - OX1 orexin/hypocretin receptor activation of phospholipase D.
AB  - BACKGROUND AND PURPOSE: Orexin receptors potently signal to lipid messenger
      systems, and our previous studies have suggested that PLD would be one of these.
      We thus wanted to verify this by direct measurements and clarify the molecular
      mechanism of the coupling. EXPERIMENTAL APPROACH: Orexin receptor-mediated PLD
      activation was investigated in CHO cells stably expressing human OX(1)  orexin
      receptors using [(14) C]-oleic acid-prelabelling and the transphosphatidylation
      assay. KEY RESULTS: Orexin stimulation strongly increased PLD activity - even
      more so than the phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate), a
      highly potent activator of PLD. Both orexin and TPA responses were mediated by
      PLD1. Orexin-A and -B showed approximately 10-fold difference in potency, and the
      concentration-response curves were biphasic. Using pharmacological inhibitors and
      activators, both orexin and TPA were shown to signal to PLD1 via the novel PKC
      isoform, PKCdelta. In contrast, pharmacological or molecular biological
      inhibitors of Rho family proteins RhoA/B/C, cdc42 and Rac did not inhibit the
      orexin (or the TPA) response, nor did the molecular biological inhibitors of PKD.
      In addition, neither cAMP elevation, Galpha(i/o)  nor Gbetagamma seemed to play
      an important role in the orexin response. CONCLUSIONS AND IMPLICATIONS:
      Stimulation of OX(1)  receptors potently activates PLD (probably PLD1) in CHO
      cells and this is mediated by PKCdelta but not other PKC isoforms, PKDs or Rho
      family G-proteins. At present, the physiological significance of orexin-induced
      PLD activation is unknown, but this is not the first time we have identified
      PKCdelta in orexin signalling, and thus some specific signalling cascade may
      exist between orexin receptors and PKCdelta.

PMID- 21718305
TI  - Receptor binding mode and pharmacological characterization of a potent and
      selective dual CXCR1/CXCR2 non-competitive allosteric inhibitor.
AB  - BACKGROUND AND PURPOSE: DF 2156A is a new dual inhibitor of IL-8 receptors CXCR1
      and CXCR2 with an optimal pharmacokinetic profile. We characterized its binding
      mode, molecular mechanism of action and selectivity, and evaluated its
      therapeutic potential. EXPERIMENTAL APPROACH: The binding mode, molecular
      mechanism of action and selectivity were investigated using chemotaxis of L1.2
      transfectants and human leucocytes, in addition to radioligand and [(35) S]
      GTPgammaS binding approaches. The therapeutic potential of DF 2156A was evaluated
      in acute (liver ischaemia and reperfusion) and chronic (sponge-induced
      angiogenesis) experimental models of inflammation. KEY RESULTS: A network of
      polar interactions stabilized by a direct ionic bond between DF 2156A and Lys(99)
      on CXCR1 and the non-conserved residue Asp(293) on CXCR2 are the key determinants
      of DF 2156A binding. DF 2156A acted as a non-competitive allosteric inhibitor
      blocking the signal transduction leading to chemotaxis without altering the
      binding affinity of natural ligands. DF 2156A effectively and selectively
      inhibited CXCR1/CXCR2-mediated chemotaxis of L1.2 transfectants and leucocytes.
      In a murine model of sponge-induced angiogenesis, DF 2156A reduced leucocyte
      influx, TNF-alpha production and neovessel formation. In vitro, DF 2156A
      prevented proliferation, migration and capillary-like organization of HUVECs in
      response to human IL-8. In a rat model of liver ischaemia and reperfusion (I/R)
      injury, DF 2156A decreased PMN and monocyte-macrophage infiltration and
      associated hepatocellular injury. CONCLUSION AND IMPLICATIONS: DF 2156A is a non
      competitive allosteric inhibitor of both IL-8 receptors CXCR1 and CXCR2. It
      prevented experimental angiogenesis and hepatic I/R injury in vivo and,
      therefore, has therapeutic potential for acute and chronic inflammatory diseases.

PMID- 21718306
TI  - Treatment of depressive-like behaviour in Huntington's disease mice by chronic
      sertraline and exercise.
AB  - BACKGROUND AND PURPOSE: Depression is the most common psychiatric disorder in
      Huntington's disease (HD) patients. Women are more prone to develop depression
      and such susceptibility might be related to 5-hydroxytryptaminergic
      (serotonergic) dysregulation. EXPERIMENTAL APPROACH: We performed tests of
      depression-related behaviours on female R6/1 HD mice that had been chronically
      treated with sertraline or provided with running-wheels. Functional assessments
      of 5-HT(1A) and 5-HT(2A) receptors were performed by measuring behavioural and
      physiological responses following administration of specific agonists, in
      combination with analysis of hippocampal gene expression. Finally we assessed the
      effect of exercise on hippocampal cell proliferation. KEY RESULTS: Female HD mice
      recorded increased immobility time in the forced-swimming test, reduced saccharin
      preference and a hyperthermic response to stress compared with wild-type animals.
      These alterations were improved by chronic sertraline treatment. Wheel-running
      also resulted in similar improvements with the exception of saccharin preference
      but failed to correct the hippocampal cell proliferation deficits displayed by HD
      mice. The benefits of sertraline treatment and exercise involved altered 5-HT(1A)
      autoreceptor function, as demonstrated by modulation of the exaggerated 8-OH-DPAT
      induced hypothermia exhibited by female HD mice. On the other hand, sertraline
      treatment was unable to restore the reduced 5-HT(1A) and 5-HT(2) heteroceptor
      function observed in HD animals. CONCLUSIONS AND IMPLICATIONS: We report for the
      first time a crucial role for 5-HT(1A) autoreceptor function in mediating the sex
      specific depressive-like phenotype of female R6/1 HD mice. Our data further
      support a differential effect of chronic sertraline treatment and exercise on
      hippocampal cell proliferation despite common behavioural benefits.

PMID- 21718307
TI  - 17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel
      vanilloid 3 leading to peripheral antinociception.
AB  - BACKGROUND AND PURPOSE: Transient receptor potential ion channel vanilloid 3
      (TRPV3) is expressed in skin keratinocytes and plays an important role in thermal
      and chemical nociceptions in the periphery. The presence of TRPV3 inhibitors
      would improve our understanding of TRPV3 function and help to develop receptor
      specific analgesics. However, little is known about physiological substances that
      specifically inhibit TRPV3 activity. Here, we investigated whether 17(R)-resolvin
      D1 (17R-RvD1), a naturally occurring pro-resolving lipid specifically affects
      TRPV3 activity. EXPERIMENTAL APPROACH: We examined the effect of 17R-RvD1 on
      sensory TRP channels using Ca(2+) imaging and whole cell electrophysiology
      experiments in a HEK cell heterologous expression system, cultured sensory
      neurons and keratinocytes. We also examined changes in sensory TRP agonist
      specific acute licking/flicking or flinching behaviours and mechanical and
      thermal pain behaviours using Hargreaves, Randall-Selitto and von Frey assay
      systems in the absence and presence of inflammation. KEY RESULTS: We showed that
      17R-RvD1 specifically suppresses TRPV3-mediated activity at nanomolar and
      micromolar concentrations. The voltage-dependence of TRPV3 activation by camphor
      was shifted rightwards by 17R-RvD1, which indicates its inhibitory mechanism is
      as a result of a shift in voltage-dependence. Consistently, TRPV3-specific acute
      pain behaviours were attenuated by locally injected 17R-RvD1. Moreover, the
      administration of 17R-RvD1 significantly reversed the thermal hypersensitivity
      that occurs during an inflammatory response. Knockdown of epidermal TRPV3 blunted
      these antinociceptive effects of 17R-RvD1. CONCLUSIONS AND IMPLICATIONS: 17R-RvD1
      is a novel natural inhibitory substance specific for TRPV3. The results of our
      behavioural studies suggest that 17R-RvD1 has acute analgesic potential via TRPV3
      specific mechanisms.

PMID- 21718308
TI  - Amplified NO/cGMP-mediated relaxation and ryanodine receptor-to-BKCa channel
      signalling in corpus cavernosum smooth muscle from phospholamban knockout mice.
AB  - BACKGROUND AND PURPOSE: Relaxation of corpus cavernosum smooth muscle (CCSM) is
      induced by NO. NO promotes the formation of cGMP, which activates cGMP-dependent
      protein kinase I (PKGI). The large conductance calcium-activated potassium
      (BK(Ca) ) channel is regarded as a major target of NO/cGMP signalling; however,
      the mechanism of BK(Ca) activation remains unclear. The aim of the present study
      was to determine whether sarcoplasmic reticulum (SR) Ca(2+) load and Ca(2+)
      release from the SR via ryanodine receptors (RyRs) is important for BK(Ca)
      channel activation in response to NO/cGMP. EXPERIMENTAL APPROACH: In vitro
      myography was performed on CCSM strips from wild-type and PLB knockout (PLB(-/-))
      mice to evaluate contraction and relaxation in response to pharmacological agents
      and electrical field stimulation (EFS). KEY RESULTS: In CCSM strips from PLB(-/-)
      mice, a model of increased SR Ca(2+) load, contractile force in response to EFS
      or phenylephrine (PE) was increased by nearly 100%. EFS of strips precontracted
      with PE induced transient relaxation in CCSM, an effect that was significantly
      larger in PLB(-/-) strips. Likewise, the relaxation of PE-induced contraction in
      response to SNP and cGMP was greater in PLB(-/-) , as demonstrated by a shift in
      the concentration-response curve towards lower concentrations. Blocking RyRs and
      BK(Ca) channels diminished the induced relaxations and eliminated the difference
      between wild-type and PLB(-/-). CONCLUSIONS AND IMPLICATIONS: NO/cGMP activates
      BK(Ca) channels through RyR-mediated Ca(2+) release. This signalling pathway is
      responsible for approximately 40% of the NO/cGMP effects and is amplified by
      increased SR Ca(2+) concentrations.

PMID- 21718309
TI  - Translational approaches targeting the p53 pathway for anti-cancer therapy.
AB  - The p53 tumour suppressor blocks cancer development by triggering apoptosis or
      cellular senescence in response to oncogenic stress or DNA damage. Consequently,
      the p53 signalling pathway is virtually always inactivated in human cancer cells.
      This unifying feature has commenced tremendous efforts to develop p53-based anti
      cancer therapies. Different strategies exist that are adapted to the mechanisms
      of p53 inactivation. In p53-mutated tumours, delivery of wild-type p53 by
      adenovirus-based gene therapy is now practised in China. Also, remarkable
      progress has been made in the development of p53-binding drugs that can rescue
      and reactivate the function of mutant or misfolded p53. Other biologic approaches
      include the development of oncolytic viruses that are designed to specifically
      replicate in and kill p53-defective cells. Inactivation of wt-p53 frequently
      results from dysregulation of MDM2, an E3 ligase that regulates p53 levels. Small
      molecule drugs that inhibit the interaction of MDM2 and p53 and block p53
      degradation are currently tested in clinical trials. This survey highlights the
      recent developments that attempt to modulate the function of p53 and outlines
      strategies that are being investigated for pharmacological intervention in the
      p53 pathway.

PMID- 21718310
TI  - Consequences of splice variation on Secretin family G protein-coupled receptor
      function.
AB  - The Secretin family of GPCRs are endocrine peptide hormone receptors that share a
      common genomic organization and are the subject of a wide variety of alternative
      splicing. All GPCRs contain a central seven transmembrane domain responsible for
      transducing signals from the outside of the cell as well as extracellular amino
      and intracellular carboxyl termini. Members of the Secretin receptor family have
      a relatively large N-terminus and a variety of lines of evidence support a common
      mode of ligand binding and a common ligand binding fold. These receptors are best
      characterized as coupling to intracellular signalling pathways via G(alphas) and
      G(alphaq) but are also reported to couple to a multitude of other signalling
      pathways. The intracellular loops are implicated in regulating the interaction
      between the receptor and heterotrimeric G protein complexes. Alternative splicing
      of exons encoding both the extracellular N-terminal domain as well as the
      extracellular loops of some family members has been reported and as expected
      these splice variants display altered ligand affinity as well as differential
      activation by endogenous ligands. Various forms of alternative splicing have also
      been reported to alter intracellular loops 1 and 3 as well as the C-terminus and
      as one might expect these display differences in signalling bias towards
      downstream effectors. These diverse pharmacologies require that the physiological
      role of these splice variants be addressed but should provide unique
      opportunities for drug design and development.

PMID- 21718311
TI  - Emodin induces chloride secretion in rat distal colon through activation of mast
      cells and enteric neurons.
AB  - BACKGROUND AND PURPOSE: Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an
      active component of many herb-based laxatives. However, its mechanism of action
      is unclear. The aim of the present study was to investigate the role of mast
      cells and enteric neurons in emodin-induced ion secretion in the rat colon.
      EXPERIMENTAL APPROACH: Short-circuit current (I(SC)) recording was used to
      measure epithelial ion transport. A scanning ion-selective electrode technique
      was used to directly measure Cl(-) flux (J(Cl)-) across the epithelium. RIA was
      used to measure emodin-induced histamine release. KEY RESULTS: Basolateral
      addition of emodin induced a concentration-dependent increase in I(SC) in colonic
      mucosa/submucosa preparations, EC(50) 75 uM. The effect of emodin was blocked by
      apically applied glibenclamide, a Cl(-) channel blocker, and by basolateral
      application of bumetanide, an inhibitor of the Na(+) -K(+) -2Cl(-) cotransporter.
      Emodin-evoked J(Cl)- in mucosa/submucosa preparations was measured by scanning
      ion-selective electrode technique, which correlated to the increase in I(SC) and
      was significantly suppressed by glibenclamide and bumetanide. Pretreatment with
      tetrodotoxin and the muscarinic receptor antagonist atropine had no effect on
      emodin-induced DeltaI(SC) in mucosa-only preparations, but significantly reduced
      emodin-induced DeltaI(SC) and J(Cl)- in mucosa/submucosa preparations. The COX
      inhibitor indomethacin, the mast cell stabilizer ketotifen and H(1) receptor
      antagonist pyrilamine significantly reduced emodin-induced DeltaI(SC) in mucosa
      and mucosa/submucosa preparations. The H(2) receptor antagonist cimetidine
      inhibited emodin-induced DeltaI(SC) and J(Cl)- only in the mucosa/submucosa
      preparations. Furthermore, emodin increased histamine release from the colonic
      mucosa/submucosa tissues. CONCLUSIONS AND IMPLICATIONS: The results suggest that
      emodin-induced colonic Cl(-) secretion involves mast cell degranulation and
      activation of cholinergic and non-cholinergic submucosal neurons.

PMID- 21718312
TI  - Anti-inflammatory effects of selective glucocorticoid receptor modulators are
      partially dependent on up-regulation of dual specificity phosphatase 1.
AB  - BACKGROUND AND PURPOSE: It is thought that the anti-inflammatory effects of
      glucocorticoids (GCs) are largely due to GC receptor (GR)-mediated
      transrepression of NF-kappaB and other transcription factors, whereas side
      effects are caused by activation of gene expression (transactivation). Selective
      GR modulators (SGRMs) that preferentially promote transrepression should retain
      anti-inflammatory properties whilst causing fewer side effects. Contradicting
      this model, we found that anti-inflammatory effects of the classical GC
      dexamethasone were partly dependent on transactivation of the dual specificity
      phosphatase 1 (DUSP1) gene. We wished to determine whether anti-inflammatory
      effects of SGRMs are also mediated by DUSP1. EXPERIMENTAL APPROACH: Dissociated
      properties of two SGRMs were confirmed using GR- and NF-kappaB-dependent
      reporters, and capacity to activate GC-responsive elements of the DUSP1 gene was
      tested. Effects of SGRMs on the expression of DUSP1 and pro-inflammatory gene
      products were assessed in various cell lines and in primary murine Dusp1(+/+) 
      and Dusp1(-/-) macrophages. KEY RESULTS: The SGRMs were able to up-regulate DUSP1
      in several cell types, and this response correlated with the ability of the
      compounds to suppress COX-2 expression. Several anti-inflammatory effects of
      SGRMs were ablated or significantly impaired in Dusp1(-/-)  macrophages.
      CONCLUSIONS AND IMPLICATIONS: Like dexamethasone, SGRMs appear to exert anti
      inflammatory effects partly via the up-regulation of DUSP1. This finding has
      implications for how potentially therapeutic novel GR ligands are identified and
      assessed.

PMID- 21718313
TI  - Increased interleukin-10 production by ASC-deficient CD4+ T cells impairs
      bystander T-cell proliferation.
AB  - Apoptosis-associated speck-like protein containing a caspase recruitment domain
      (ASC) is an important component of the inflammasome, functioning as an adaptor
      protein that facilitates the recruitment and activation of procaspases that in
      turn promote the maturation of interleukin-1beta (IL-1beta) and IL-18. Despite
      initial focus on the inflammatory properties of ASC there is emerging evidence
      that highlights the importance of ASC in facilitating adaptive immune responses.
      However, the cellular and molecular basis for the involvement of ASC in adaptive
      immunity remains largely unexplored. We have previously demonstrated that
      activated ASC-deficient T cells have dampened proliferative responses. We have
      therefore explored the underlying cellular mechanism(s) by which ASC regulates T
      cell proliferation. We show that under activating conditions (anti-CD3/CD28
      stimulation) in bulk T-cell cultures the presence of ASC(-/-) CD4(+) T cells is
      sufficient to suppress the proliferative responses of neighbouring T cells.
      Furthermore, ASC(-/-) CD4(+) T cells upon activation exhibit a suppressive
      cytokine profile, with elevated production of IL-10 and reduced secretion of T
      helper type 1 cytokines, interferon-gamma and IL-2. This increase in IL-10
      secretion within the activated ASC(-/-) CD4(+) T-cell compartment was not
      associated with a proportional increase in conventional Foxp3(+) regulatory T
      (Treg) cells. Interestingly, when equal numbers of fluorescence-activated cell
      sorted ASC(+/+) and ASC(-/-) Treg cells (CD4(+) CD44(intermediate/high) CD25(+))
      were activated in vitro, the ASC(-/-) fraction produced significantly more IL-10
      than their wild-type counterparts, suggesting that ASC(-/-) Treg cells have
      greater suppressive capacity. Collectively, these results imply that the ASC may
      influence the development and functioning of Treg cells.

PMID- 21718314
TI  - Control of early stages in invariant natural killer T-cell development.
AB  - Natural killer T (NKT) cells develop in the thymus from the same precursors as
      conventional CD4(+) and CD8(+) alphabeta T cells, CD4(+)  CD8(+) double-positive
      cells. In contrast to conventional alphabetaT cells, which are selected by MHC
      peptide complexes presented by thymic epithelial cells, invariant NKT cells are
      selected by lipid antigens presented by the non-polymorphic, MHC I-like molecule
      CD1d, present on the surface of other double-positive thymocytes, and require
      additional signals from the signalling lymphocytic-activation molecule (SLAM)
      family of receptors. In this review, we provide a discussion of recent findings
      that have modified our understanding of the NKT cell developmental programme,
      with an emphasis on events that affect the early stages of this process. This
      includes factors that control double-positive thymocyte lifespan, and therefore
      the ability to generate the canonical Valpha rearrangements that characterize
      this lineage, as well as the signal transduction pathways engaged downstream of
      the T-cell receptor and SLAM molecules.

PMID- 21718315
TI  - Novel approach for interleukin-23 up-regulation in human dendritic cells and the
      impact on T helper type 17 generation.
AB  - Interleukin-23 (IL-23) is important for T helper type 17 (Th17) responses and
      strategies to regulate IL-23 in human dendritic cells (DC) are limited. This
      study describes a novel means to control IL-23 secretion by conditioning DC with
      a phosphatidyl inositol 3-kinase inhibitor Wortmannin (WM). Treatment of monocyte
      derived DC with WM increased Toll-like receptor (TLR) -dependent IL-23 secretion
      10-fold and IL-12p70 twofold, but IL-27 was unaffected. The effect of WM was
      restricted to TLR3/4 pathways, did not occur through TLR2, TLR7/8 or Dectin-1,
      and was characterized by increased p19, p35 and p40 transcription. These
      responses were not solely dependent on phosphatidyl inositol 3-kinase as the
      alternative inhibitor LY294002 did not modulate IL-23 production. The normal
      patterns of activation of mitogen-activated protein kinase pathways were
      unaffected by WM-conditioning but IL-23 secretion required p38, ERK and JNK
      pathways. Importantly, this effect was manifest in populations of blood DC.
      Conditioning freshly isolated myeloid DC with WM before TLR3 or TLR4 triggering
      resulted in high levels of IL-23 secretion and an absence of IL-12p70. These WM
      conditioned myeloid DC were highly effective at priming Th17 responses from naive
      CD4(+) T cells. Our findings provide a novel means to generate IL-23-rich
      environments and Th17 responses and suggest as yet unidentified regulatory
      factors, identification of which will provide new approaches to control IL-23
      dependent immunity in infectious disease, autoimmunity and malignancy.

PMID- 21718316
TI  - Sensitivity and ex vivo validation of finite element models of the domestic pig
      cranium.
AB  - A finite element (FE) validation and sensitivity study was undertaken on a modern
      domestic pig cranium. Bone strain data were collected ex vivo from strain gauges,
      and compared with results from specimen-specific FE models. An isotropic,
      homogeneous model was created, then input parameters were altered to investigate
      model sensitivity. Heterogeneous, isotropic models investigated the effects of a
      constant-thickness, stiffer outer layer (representing cortical bone) atop a more
      compliant interior (representing cancellous bone). Loading direction and
      placement of strain gauges were also varied, and the use of 2D membrane elements
      at strain gauge locations as a method of projecting 3D model strains into the
      plane of the gauge was investigated. The models correctly estimate the loading
      conditions of the experiment, yet at some locations fail to reproduce correct
      principal strain magnitudes, and hence strain ratios. Principal strain
      orientations are predicted well. The initial model was too stiff by approximately
      an order of magnitude. Introducing a compliant interior reported strain
      magnitudes more similar to the ex vivo results without notably affecting strain
      orientations, ratios or contour patterns, suggesting that this simple
      heterogeneity was the equivalent of reducing the overall stiffness of the model.
      Models were generally insensitive to moderate changes in loading direction or
      strain gauge placement, except in the squamosal portion of the zygomatic arch.
      The use of membrane elements made negligible differences to the reported strains.
      The models therefore seem most sensitive to changes in material properties, and
      suggest that failure to model local heterogeneity in material properties and
      structure of the bone may be responsible for discrepancies between the
      experimental and model results. This is partially attributable to a lack of
      resolution in the CT scans from which the model was built, and partially due to
      an absence of detailed material properties data for pig cranial bone. Thus,
      caution is advised when using FE models to estimate absolute numerical values of
      breaking stress and bite force unless detailed input parameters are available.
      However, if the objective is to compare relative differences between models, the
      fact that the strain environment is replicated well means that such
      investigations can be robust.

PMID- 21718318
TI  - Fundamentals of PET and PET/CT imaging.
AB  - In this review, the fundamental principles of fluorodeoxyglucose (FDG) positron
      emission tomography (PET) and FDG PET/computed tomography (CT) imaging have been
      described. The basic physics of PET instrumentation, radiotracer chemistry, and
      the artifacts, as well as normal physiological or benign pathological variants,
      have been described and presented to the readers in a lucid manner to enable them
      an easy grasp of the fundamentals of the subject. Finally, we have outlined the
      current developments in quantitative PET imaging, including dual time point and
      delayed PET imaging, time-of-flight technology in PET imaging and partial volume
      correction, and global disease assessment with their potential of being
      incorporated into the assessment of benign and malignant disorders.

PMID- 21718317
TI  - A divergent myeloid dendritic cell response at virus set-point predicts disease
      outcome in SIV-infected rhesus macaques.
AB  - BACKGROUND: The mechanism for loss of myeloid dendritic cells (mDCs) from the
      circulation in HIV-infected individuals and its relationship to disease
      progression is not understood. METHODS: A longitudinal analysis of the mDC
      response in blood and lymph nodes during the first 12 weeks of infection was
      performed in a cohort of SIVmac251-infected rhesus macaques with different
      disease outcomes. RESULTS: Monkeys that rapidly progressed to disease or had long
      term stable infection had significant losses or increases, respectively, in blood
      mDCs that were inversely correlated with virus load at set-point. The loss of
      mDCs from progressor animals was associated with evidence of an increase in
      CCR7/CCL19-dependent mDC recruitment to lymph nodes and an increase in mDC
      apoptosis. CONCLUSIONS: mDC recruitment to and death within inflamed lymph nodes
      may contribute to disease progression in SIV infection, whereas mobilization
      without increased recruitment to lymph nodes may promote disease control.

PMID- 21718319
TI  - Positron emission tomography findings in clinical mimics of lymphoma.
AB  - The use of positron emission tomography (PET) scans is rapidly evolving in the
      diagnosis, treatment, and surveillance of lymphoma. However, significant
      challenges exist in differentiating lymphomatous from benign lesions. Herein we
      describe the clinical and radiographic uptake patterns seen in common clinical
      mimics of lymphoma, including infections such as human immunodeficiency virus and
      tuberculosis, inflammatory disorders such as sarcoidosis and connective tissue
      disorders, and other benign lymphoproliferative disorders such as Kikuchi's
      disease and Rosai-Dorfman disease. The clinical utility of PET scans has
      encompassed varying fields, not just oncology. Future challenges with the use of
      improved radiopharmaceuticals in accurately defining and differentiating lesions
      that would affect clinical treatment would be of paramount importance.

PMID- 21718320
TI  - FDG PET for rheumatoid arthritis: basic considerations and whole-body PET/CT.
AB  - [(18) F]Fluorodeoxyglucose (FDG) is a tracer for glucose metabolism. Its
      distribution is not specific to cancer cells but is also observed in inflammatory
      tissue, including macrophages, capillaries, and fibroblasts. Rheumatoid arthritis
      (RA) is a systemic, chronic inflammation of the joints resulting in synovitis.
      The disease is characterized by fibrovascular proliferation leading to the
      formation of a pannus and causing high FDG uptake. Several clinical studies of RA
      have demonstrated that FDG uptake in affected joints reflects the disease
      activity of RA, with strong correlations between uptake and various clinical
      parameters having been noted. Furthermore, the use of FDG PET for the sensitive
      detection and monitoring of the response to RA therapy has been reported. FDG
      PET/computed tomography (CT) enables the detailed evaluation of disease in large
      joints throughout the whole body, which is a unique advantage of PET/CT. FDG
      PET/CT can also be used to detect high-risk disease complications, such as
      atlanto-axial joint involvement, at an early stage. The possible contribution of
      FDG PET to the management of patients with RA remains to be studied in detail.

PMID- 21718321
TI  - PET/CT imaging in inflammatory myopathies.
AB  - Inflammatory muscle diseases are a group of muscle disorders characterized by
      muscle weakness, fatigue, and an association with malignancy and paraneoplastic
      syndrome. A diagnosis of idiopathic inflammatory myopathy is suggested by
      abnormal myometry and rising creatine kinase, but tissue diagnosis is also
      needed. Magnetic resonance imaging (MRI) helps localize the appropriate site of
      biopsy, demonstrate the extent of muscle involvement, and monitor the response to
      therapy. However, the sensitivity of magnetic resonance (MR) is limited, and
      whole-body imaging is still far from routine. [(18) F]Fluoro-desoxy-glucose (FDG)
      positron emission tomography (PET)/computed tomography (CT) is currently the
      ultimate metabolic imaging technique for the management of cancer. It has also
      been shown to detect inflammatory conditions and to monitor their response to
      treatment. The use of FDG PET in screening for underlying malignancies is widely
      reported and recommended in patients with paraneoplastic syndrome. Unfortunately,
      only a few reports have been published to show the value of FDG PET in
      inflammatory muscle diseases, which as we show herein, deserve further pursuit.

PMID- 21718322
TI  - PET scanning in sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disorder that most commonly presents
      with pulmonary involvement. The diagnosis is suggested on the basis of clinical
      and radiologic manifestations and is supported by the histological demonstration
      of noncaseating granulomas in affected tissues. Different imaging modalities,
      including chest radiography, X-rays, computed tomography, magnetic resonance
      imaging, and (67) Ga scintigraphy are currently employed to help diagnose and
      help plan treatment strategy in sarcoidosis patients. Here, we discuss the
      potential role of positron emission tomography in the diagnosis, assessment of
      disease activity, and management of patients with sarcoidosis. We also point out
      some of the limitations of this technique.

PMID- 21718323
TI  - The role of positron emission tomography in the evaluation of inflammatory bowel
      disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects
      the gastrointestinal tract. Information obtained from a clinical history,
      physical exam, laboratory testing, imaging studies, and endoscopic evaluations
      must be combined to accurately diagnose IBD. Further testing often becomes
      necessary to evaluate symptom relapse in patients with an established IBD
      diagnosis. Endoscopy, while effective in assessing mucosal disease, is invasive
      and associated with inherent risks. Positron emission tomography (PET) is an
      effective, noninvasive tool for the evaluation of active inflammation. This
      review will focus on the role of PET imaging in the evaluation and management of
      IBD.

PMID- 21718324
TI  - PET in vasculitis.
AB  - [(18) F]Fluorodeoxyglucose positron emission tomography (FDG PET) can be used to
      visualize large-vessel inflammation in giant-cell arteritis, Takayasu arteritis,
      and other types of aortitis. In patients with symptoms compatible with
      polymyalgia rheumatica, findings of increased FDG-uptake in the shoulders, hips,
      as well as the spinous processes of the cervical and lumbar spine, may suggest
      this diagnosis. In patients with giant-cell arteritis, there is increased
      metabolic activity within the aortic wall on FDG PET scintigraphy, indicating
      inflammation of the aorta, which may be a predictor of a higher potential for
      aortic dilatation.

PMID- 21718325
TI  - PET/CT imaging in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is the classical immune-complex disease.
      Involvement of vital organs, particularly the kidneys and brain, accounts for
      significant morbidity and mortality. A number of imaging tools are currently
      available for evaluation of inflammatory conditions. By targeting the increased
      glucose uptake of infiltrating granulocytes and tissue macrophages, positron
      emission tomography with fluorine-18 fluorodeoxyglucose ([(18) F]FDG PET/CT) has
      been shown to delineate inflammation with high sensitivity. Because activated
      lymphocytes have increased glucose metabolism, [(18) F]FDG PET has been
      successfully used to visualize large concentrations of these cells in lymphoid
      organs where antigen presentation and lymphocyte activation occur. Widespread
      increased FDG uptake in lymph nodes of patients with active SLE, as well as
      increased thymic uptake, has been described. The most prevalent and dramatic
      PET/CT finding in neuropsychiatric SLE (NP-SLE) patients is parieto-occipital
      hypometabolism. In conclusion, PET/CT has become an excellent ancillary tool to
      assess disease activity and prognosis in SLE patients.

PMID- 21718326
TI  - PET/CT in diagnosis of dementia.
AB  - Clinical use of positron emission tomography (PET) is now well established in
      neurodegenerative disorders, especially in the diagnosis of dementia. Measurement
      of cerebral glucose metabolism is of significant value, and it facilitates early
      diagnosis, appropriate differential diagnosis, and the evaluation of drug
      treatment in patients with dementia. In addition, tracers offer new perspectives
      for studying the neuropathology of underlying dementia, such as the accumulation
      of amyloid proteins, tau-proteins, or the presence of neuroinflammation. Finally,
      PET tracer studies of different neurotransmitter systems in dementia may not only
      increase the understanding of pathophysiologic mechanisms of the different
      disorders, but also improve diagnostic accuracy. In conclusion, PET imaging with
      different tracers offers reliable biomarkers in dementia, which can assist
      clinicians in the diagnosis of different dementing disorders, especially in the
      situation of overlapping phenotypes.

PMID- 21718328
TI  - PET and PET/CT in cardiovascular disease.
AB  - The present review provides an overview of the role of cardiac positron emission
      tomography in the diagnosis and management of cardiovascular disease. It expands
      on the relative advantages and disadvantages over other imaging modalities as
      well as the available evidence supporting its value in the diagnosis and
      management of patients with coronary artery disease, the assessment of myocardial
      viability, and evaluation of the cardiac sympathetic nervous system. Furthermore,
      the recent developments, such as the implementation of high-end computed
      tomography devices to form hybrid systems, and the advances of molecular imaging
      probes in experimental applications are briefly discussed.

PMID- 21718327
TI  - PET/CT in diagnosis of movement disorders.
AB  - Molecular imaging with PET offers a broad variety of tools supporting the
      diagnosis of movement disorders. The more widely applied PET imaging techniques
      have focused on the assessment of neurotransmitter systems, predominantly the pre
      and postsynaptic dopaminergic system. Additionally, PET imaging with [(18)
      F]fluorodeoxyglucose has been extensively used to assess local synaptic activity
      in the resting state and to highlight local changes in brain metabolism
      accompanying changes in neural activity in movement disorders. PET imaging has
      provided us with diagnostic agents as well as tools for evaluation of novel
      therapeutics, and has served as a powerful means for revealing in vivo changes at
      different stages of movement disorders and within the course of an individual
      patient's illness.

PMID- 21718329
TI  - Positron emission tomography for the evaluation and treatment of cardiomyopathy.
AB  - Congestive heart failure accounts for tremendous morbidity and mortality
      worldwide. There are numerous causes of cardiomyopathy, the most common of which
      is coronary artery disease. Positron emission tomography (PET) has an established
      and expanding role in the evaluation of patients with cardiomyopathy. The
      specific application of PET to hypertrophic cardiomyopathy, cardiac sarcoidosis,
      and diabetic cardiomyopathy has been studied extensively and promises to be a
      useful tool for managing these patients. Furthermore, evaluating the efficacy of
      standard treatments for congestive heart failure is important as health care
      costs continue to rise. Recently, there have been significant developments in the
      field of cardiovascular stem cell research. Familiarity with the mechanisms by
      which stem cells benefit patients with cardiovascular disease is the key to
      understanding these advances. Molecular imaging techniques including PET/CT
      imaging play an important role in monitoring stem cell therapy in both animals
      and humans. These noninvasive imaging techniques will be highlighted in this
      paper.

PMID- 21718330
TI  - PET/CT imaging in infectious conditions.
AB  - New aggressive pathogens are responsible for the increasing incidence and
      difficult management of infections. Modern epidemics such as diabetes are
      frequently complicated by severe infections with subsequent high morbidity.
      Diagnosis (essentially early detection of infection) and also management decision
      making pose clinical challenges. Many resources are invested in developing
      precise, noninvasive diagnostic tests and efficient therapies for infectious
      processes. Nuclear medicine procedures are part of the evaluation armamentarium
      of patients with suspected or confirmed infection. Their strength relies on the
      fact that they are noninvasive tests that provide both functional as well as
      metabolic information early in the course of disease. Their limitations relate to
      the need for specific radiotracers and the rather low resolution of images. These
      limitations have been largely overcome by the hybrid PET/CT and SPECT/CT
      technology. PET/CT, primarily using FDG, is redefining the diagnostic work up and
      is currently leading to changes in the management of patients with suspected or
      known infections. The main indications for FDG PET/CT in infection, as well as
      updated literature results, are presented in the following review.

PMID- 21718331
TI  - Future and upcoming non-neoplastic applications of PET/CT imaging.
AB  - The role of fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the
      diagnosis, staging, and monitoring of neoplastic conditions is well established.
      The clinical utility of PET/CT has now expanded to the diagnosis of autoimmune,
      inflammatory, infectious, as well as non-neoplastic conditions, such as the
      vasculitides, atherosclerosis, and granulomatous conditions, including
      sarcoidosis and inflammatory bowel disease, in addition to a variety of
      neurologic disorders. The availability of new PET radiotracers is expected to
      expand PET/CT applications to a variety of other clinical domains. New
      radioligands for studying inflammation and neurodegenerative processes are under
      development. Here, we discuss the evolving potential role of PET imaging for the
      evaluation and monitoring of miscellaneous conditions, including osteoarthritis,
      interstitial lung disease, vascular thromboses, and osteoporosis.

PMID- 21718332
TI  - Lack of effect of ustekinumab in treatment of allergic contact dermatitis.
AB  - BACKGROUND: Allergic contact dermatitis is a chronic inflammatory T cell mediated
      disease that can be recalcitrant to existing treatments. Ustekinumab is a
      monocloncal antibody blocking IL-12 and IL-23, shown to be effective and safe for
      patients with psoriasis. Despite both IL-12 and IL-23 involvement in contact
      allergy, the effect of Ustekinumab on allergic contact dermatitis has not been
      reported. OBJECTIVES: To evaluate the clinical effect of Ustekinumab in patients
      with allergic contact dermatitis. METHODS: A retrospective, case cohort study of
      patients with allergic contact dermatitis treated with Ustekinumab in our
      department. RESULTS: Five patients had been treated with Ustekinumab for allergic
      contact dermatitis, with limited effect. CONCLUSION: Our observation suggests
      that, although theoretically plausible, Ustekinumab does not seem to be a
      valuable therapeutic approach for chronic allergic contact dermatitis.

PMID- 21718333
TI  - Influence of eye make-up on the perception of gaze direction.
AB  - Make-up has a beautifying effect on facial attractiveness. However, little is
      known about the role of make-up in other than social perception. Does eye make-up
      applied to a gazing face influence the perception of this gaze by others? Eye
      make-up might make an individual's gaze more recognizable by emphasizing the
      contrast of the eyes. Or make-up might make gaze less recognizable by
      transforming eyes to unnatural shapes. There were two stimulus conditions: eye
      make-up (no-eyeliner, thin-eyeliner and thick-eyeliner) and gaze direction (same
      gaze direction and different gaze directions). Participants had to make a
      recognition response indicating whether the gaze directions were the same or
      different. Results indicated that in the same gaze-direction condition, thin and
      thick-eyeliner made recognition of a persisting gaze direction easier, whereas in
      the different gaze-direction condition thick-eyeliner made it more difficult to
      recognize the changes in gaze direction. These findings suggested a significant
      role of make-up in facial processing.

PMID- 21718334
TI  - Generalized pulp stones: report of a case with 6-year follow-up.
AB  - AIM: To present a mildly mentally retarded patient with generalized pulp stone
      formation and the six-year follow-up and to discuss the differential diagnosis of
      the case. SUMMARY: Pulp stones were radiographically detected in the pulp chamber
      of all permanent teeth in a 25-year-old woman with mild mental retardation who
      presented for endodontic treatment on tooth no 11 (FDI). The patient's medical,
      dental and family history was noncontributory. The pulp stone in the pulp chamber
      of tooth no 11 was removed during canal filing, and root canal treatment
      completed uneventfully. Six years later, the patient was re-evaluated and the
      pulp stones were unchanged radiographically. The patient's family history, facial
      phenotype and karyotype as well as the radiographic, laboratory and physical
      examination were not consistent with any of the known genetic syndromes
      associated with generalized pulp stones. Molecular analysis for the DSPP gene
      proved negative. The aetiology of this case remains unknown. KEY POINTS:
      Generalized pulp stones occur rarely; Such patients should be referred for
      genetic evaluation because pulp stones are mostly associated with genetic dentine
      defects; Pulp stones may hinder root canal treatment; Pulp stones may remain
      unchanged overtime.

PMID- 21718335
TI  - Management of a talon cusp using mineral trioxide aggregate.
AB  - AIM: To report on the successful conservative management of three patients having
      a talon cusp with pulpal involvement using mineral trioxide aggregate (MTA).
      SUMMARY: Mineral trioxide aggregate was used to induce hard-tissue formation
      following the direct pulp capping of a resected talon cusp in three cases. KEY
      LEARNING POINTS: * Talon cusp is an odontogenic anomaly which can cause occlusal
      interferences, displacement of the affected tooth, caries-susceptible
      developmental grooves and speech difficulties * Direct pulp capping using MTA
      following the resection of a talon cusp is a suitable treatment option.

PMID- 21718336
TI  - Microstructure and chemical analysis of blood-contaminated mineral trioxide
      aggregate.
AB  - AIM: To test the hypothesis that blood contamination has a detrimental effect on
      the chemical properties of Mineral trioxide aggregate (MTA). METHODOLOGY: The
      effects of whole, fresh human blood on the microstructure and elemental chemistry
      of MTA were evaluated using scanning electron microscopy and energy-dispersive X
      ray analysis, respectively. The phase compositions of contaminated and
      uncontaminated MTA were also analysed using X-ray diffraction analysis. RESULTS:
      The hydration state of specimens partially mixed with blood were more complete
      than those mixed entirely with blood and less than those entirely mixed with
      water. Acicular crystals, characteristic of ettringite, were abundant in
      specimens mixed entirely with water and absent from specimens mixed partially or
      entirely with blood. Calcium hydroxide crystals were absent in specimens
      contaminated entirely with blood and the unhydrated MTA powder, but present in
      the other groups. CONCLUSION: Mixing MTA with blood resulted in the lack of
      formation of the crystalline calcium hydroxide in the early stage of the
      hydration process.

PMID- 21718337
TI  - Repair and regeneration in endodontics.
AB  - The ideal objective of treatment of established diseases, including irreversible
      pulpitis and apical periodontitis, is to achieve wound healing. Wound healing can
      result in repair or regeneration. The ultimate goal of wound healing is to
      restore the original architecture and biological function of the injured tissue
      or organ. Although humans are equipped with powerful innate and adaptive immune
      defence mechanisms, many intrinsic and extrinsic factors can affect wound
      healing. Complete regeneration following injury in humans can occur only in the
      pre-natal foetus within 24 weeks of gestation. Post-natal wounds including
      irreversible pulpitis or apical periodontitis always heal by repair or by a
      combination of repair and regeneration. Somatic cells, such as fibroblasts,
      macrophages, cementoblasts and osteoblasts, in the pulp and periapical tissues
      have limited potential for regeneration following injury and lack of telomerase.
      Wound healing of irreversible pulpitis and apical periodontitis requires
      recruitment and differentiation of progenitor/stem cells into tissue-committed
      somatic cells. Stem cell differentiation is regulated by intrinsic factors and
      extrinsic micro-environmental cues. Functionality of stem cells appears to show
      an age-related decline because of the change in intrinsic properties and
      diminished signals within the extrinsic local and systemic environment that
      modulate the function of stem cells or their progeny. Infection induces an immuno
      inflammatory response and tissue destruction, which hinders the potential of
      tissue regeneration. Therefore, prevention, early detection and treatment of
      inflammation/infection of pulpal and periapical disease can enhance regeneration
      and minimize the repair of pulpal and periapical tissues after endodontic
      therapy.

PMID- 21718338
TI  - A histological study of pulp reaction to various water/powder ratios of white
      mineral trioxide aggregate as pulp-capping material in human teeth: a double
      blinded, randomized controlled trial.
AB  - AIM: To compare the histological pulp reaction to various water/powder ratios of
      white mineral trioxide aggregate (MTA) as a pulp-capping material in healthy
      human teeth. METHODOLOGY: Twenty-nine disease-free maxillary and mandibular third
      molar teeth, scheduled for extraction, were exposed mechanically and then capped
      with 0.28, 0.33 and 0.40 water/powder ratios of white MTA (ProRoot; Dentsply
      Maillefer, Ballaigues, Switzerland) and restored with glass ionomer. After 30
      days, the teeth were extracted, resected apically and immersed in 10% formalin.
      For histological processing, the teeth were sectioned buccolingually in 5-MUm
      thick slices, stained with Haematoxylin and Eosin and evaluated by a light
      microscope. Samples were evaluated for intensity and type of inflammation,
      presence of necrosis, as well as continuity, morphology and thickness of
      calcified bridges. The data were analysed by Kruskal-Wallis and Mann-Whitney
      tests. RESULTS: There were no significant differences in the diameter, morphology
      and continuity of the calcified bridges, intensity and type of inflammation or
      presence of necrosis (P > 0.05) in the pulps covered by MTA with various
      water/powder ratios. Two teeth failed to display a calcified bridge, and one had
      a pulp necrosis. CONCLUSION: Water-to-powder ratios of MTA had no significant
      influence on the histological outcome of direct pulp capping on healthy pulps.

PMID- 21718339
TI  - Accuracy and reproducibility of two scales in causality assessment of unexpected
      hepatotoxicity.
AB  - WHAT IS KNOWN AND OBJECTIVE: There is almost no published information about
      reliability of scales for causality assessment in hepatotoxicity at
      pharmacovigilance centres. The aim of this study was to compare two commonly used
      scales in cases of unexpected hepatotoxicity, in evaluating their accuracy and
      reproducibility at pharmacovigilance centres (in signal detection). METHODS: Two
      scales [Council for International Organizations of Medical Sciences or Rousel
      Uclaf Causality Assessment Method (CIOMS/RUCAM) and NARANJO] were compared in 19
      cases of unexpected hepatotoxicity reported during 2004-2009. Data of the cases
      (with initial clinical assessments) were collected by a network of medical
      specialists using a structured reporting form. Later, two independent observers
      assessed each case using both scales. The accuracy and reproducibility of the
      scales were analysed by Kappa weighted (Kw) test. RESULTS:   Both scales
      (CIOMS/RUCAM vs. NARANJO) showed moderate agreement with the initial clinical
      assessments (accuracy) for observer A (Kw: 0.56 vs. 0.60) and substantial
      agreement for observer B (Kw: 0.72 vs. 0.70), with high agreement between
      observers (Kw: 0.84 vs. 0.67). Both observers (A vs. B) found low agreement
      between scales (Kw: 0.21 vs. 0.50), with lower scores for the CIOMS/RUCAM scale
      in 11 and nine cases, respectively. For an early perception of unexpected serious
      reactions, the scale is more useful if it is not asked for 'previous knowledge'
      and if it gives higher causality score. WHAT IS NEW AND CONCLUSION: The
      CIOMS/RUCAM scale showed similar accuracy, but better reproducibility (agreement
      between observers) than the NARANJO scale, and therefore is recommended for use
      at pharmacovigilance centres. Fine-tuning of the CIOMS/RUCAM method could
      contribute to better detection of unexpected hepatotoxicity.

PMID- 21718340
TI  - Perceptions of patient participation amongst elderly patients with end-stage
      renal disease in a dialysis unit.
AB  - AIM: A patient's right to influence treatment and health care has been guaranteed
      by Norwegian law since 1999. The aim of this study was to explore how elderly
      patients with end-stage renal disease who are undergoing treatment with
      haemodialysis for the rest of their lives perceive patient participation in a
      dialysis unit. METHODS: This study, which was inspired by critical discourse
      analysis, drew on data derived from transcribed interviews with 11 patients.
      FINDINGS: Two discourses related to patient participation were identified. The
      first and dominant discourse was called the health-care team's power and
      dominance. Both environmental conditions and the team's practice exercised power
      and control over the patients. The patients trusted the health-care team, but
      some felt powerless and were afraid of what might happen if they refused to
      follow the instructions. The health-care team owned the knowledge and decided
      what the patients needed to know. Most of all the patients wanted dialogue about
      the future. After years of treatment, patient identity seemed to be threatened by
      this situation. The second discourse is called the patients struggling for shared
      decision-making. Some patients struggled to be involved in decision-making about
      'dry weight', diet, blood access and time of treatment when these factors
      threatened their well-being and the quality of their daily lives. CONCLUSIONS:
      The elderly patients' right to participate in their haemodialysis treatment did
      not seem to be well incorporated into the social practices of haemodialysis
      units. Changing the social practices in the dialysis units from a paternalistic
      ideology to an ideology of participation will require consideration of the
      context, the dialogue and the process of shared decision-making with the patient.

PMID- 21718341
TI  - Nurses' self-reported knowledge about and attitude to nutrition -- before and
      after a training programme.
AB  - BACKGROUND: It is well known that appropriate nutrition is vital for
      inpatientrecovery. Traditionally, nutrition is part of nurses' area of
      responsibility and as it affects mortality and morbidity, it is important that
      nurses feel responsible for, and accomplish adequate nutrition care during the
      patients' hospital stay. But putting evidence of nutritional topics into practice
      is challenging and nutrition care seems to be a low priority nursing task. AIMS:
      To investigate the impact of training programme targeted nurses with special
      responsibilities for nutrition on the nurses' knowledge of nutrition, and whether
      it enhanced their attitude to their responsibility for nutrition care in relation
      to assessment and management. METHODS: An intervention study was conducted with
      16 nurses from either medical or surgical wards who participated in a 12-month
      training programme. These nurses were divided into two groups and interviewed
      twice before and after the intervention. Focus group interviews were used to
      gather data about their daily clinical work in relation to nutrition. Deductive
      content analysis was used to analyse the described data. RESULTS: The training
      programme did have an impact on the nurses' knowledge of nutrition. It made them
      feel more secure and strengthened their ability to take responsibility for more
      nutrition management and as the results indicate, improved their awareness of
      nurse-specific treatment and their responsibility for nutrition assessment. We
      also found that nurses still have difficulty expressing their knowledge of
      nutrition using academic concepts, as they mainly use general phrases.
      CONCLUSION: The findings suggest that a short-duration training programme
      enhances nurses' awareness of nutrition care, but it is not enough to achieve the
      nurses' full understanding of their responsibility for nutrition care.

PMID- 21718342
TI  - Multiple forms of hypogonadism of central, peripheral or combined origin in males
      with Prader-Willi syndrome.
AB  - BACKGROUND: Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed
      to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is
      still unclear. OBJECTIVES: To investigate the aetiology of hypothalamic-pituitary
      gonadal axis dysfunction in PWS males. METHODS: Clinical examination and blood
      sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      testosterone, inhibin B and sexhormone-binding globulin (SHBG) were performed in
      34 PWS patients, age 5.1-42.7 years, and in 125 healthy males of same age range.
      All participants were divided into two groups : < or >=13.5 years. RESULTS:
      Pubertal PWS patients showed an arrest of pubertal development. Patients <13.5
      years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those
      >=13.5 years, 8/24 patients had normal LH and testosterone, high FSH and low
      inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH
      and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH
      but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and
      normal LH despite low testosterone. Compared with controls, patients <13.5 years
      had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular
      volume; those >=13.5 years had smaller testicular volume, near-significantly
      lower LH, testosterone, SHBG, inhibin B and higher FSH. CONCLUSION: PWS patients
      display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of
      central origin for LH and/or FSH; (ii) early primary testicular dysfunction
      (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for
      FSH-inhibin B axis and central origin for LH-T axis).

PMID- 21718343
TI  - Immunohistochemical characterization of gamma-secretase activating protein
      expression in Alzheimer's disease brains.
AB  - AIMS: A recent study showed that gamma-secretase activating protein (GSAP),
      derived from a C-terminal fragment of pigeon homolog (PION), increases amyloid
      beta (Abeta) production by interacting with presenilin-1 (PS1) and the beta
      secretase-cleaved C-terminal fragment of amyloid precursor protein (APP-CTF). In
      the study, knockdown of GSAP reduces production of Abeta and plaque formation in
      the brain of APPswe and PS1DeltaE9 double transgenic mice without affecting the
      Notch-dependent pathway. Therefore, GSAP is an ideal target for designing gamma
      secretase modulators with least side effects in Alzheimer's disease (AD).
      However, at present, the precise distribution of GSAP in AD brains remains to be
      characterized. METHODS: By immunohistochemistry, we studied GSAP expression in
      the frontal cortex and the hippocampus of 11 aged AD and 17 age-matched control
      cases. RESULTS: GSAP immunoreactivity exhibited distinct morphological features,
      such as fine granular cytoplasmic deposits, dense nodular and patchy deposits,
      beads and string-like deposits, and diffuse dot-like deposits. In both AD and
      control brains, a fairly small subset of cerebral cortical and hippocampal
      neurones expressed fine granular cytoplasmic deposits, while diffuse dot-like
      deposits were more frequently found in the neuropil and neuronal processes,
      particularly enriched in the hippocampal CA2 and CA3 regions. Among GSAP
      immunoreactive deposits, dense nodular and patchy deposits, located in the
      neuropil and closely associated with PS1 expression and Abeta deposition,
      indicated the most distinguishing features of AD pathology. CONCLUSIONS: Aberrant
      regulation of GSAP expression plays a key role in acceleration of gamma-cleavage
      of APP-CTF and accumulation of Abeta in AD brains.

PMID- 21718344
TI  - What's new in atopic eczema? An analysis of systematic reviews published in 2009
      2010.
AB  - This review provides a summary of key findings from 18 systematic reviews on
      atopic eczema, published or indexed between January 2009 and 24 August 2010.
      There was no good evidence on the possible benefit of organic food consumption
      and eczema. Maternal intake of fish or fish oil may be associated with a reduced
      risk of eczema in offspring, although further studies are needed. There is some
      evidence that partially hydrolysed infant formulas rather than standard formulas
      may be associated with a reduced risk of eczema in infants, but there are
      shortcomings in the existing evidence. An inverse relationship has been found
      between gliomas/acute lymphoblastic leukaemia and allergic disease/eczema, but
      there appears to be no association between multiple sclerosis and eczema.
      Attention deficit hyperactivity disorder does appear to be associated with
      eczema, but there is no evidence of a causal link. The risk of eczema seems to be
      increased in urban compared with rural areas. Some new evidence has suggested
      superiority of 1% pimecrolimus over potent and mild corticosteroids at 6 months
      but not 12 months, and there is some evidence for superiority of 0.03% and 0.1%
      tacrolimus over 1% pimecrolimus. An updated Cochrane Review still found no
      evidence of a benefit from any form of antistaphylococcal treatment in managing
      clinically infected or uninfected eczema. The evidence base is poor for bath
      emollients, occlusive treatments (e.g., wet and dry wraps) and woven silk
      clothing in treating eczema. In general, the methods used in most systematic
      reviews of eczema need to be reported more clearly, especially with regard to a
      more vigorous quality assessment of included studies. Included studies are
      frequently heterogeneous, proxy reporting is common, and appropriate disease
      definitions are often lacking. Better adherence to existing guidance on trial
      reporting and prospective registration of clinical trials may help improve the
      quality of studies.

PMID- 21718345
TI  - What's new in psoriasis? An analysis of guidelines and systematic reviews
      published in 2009-2010.
AB  - This review summarizes key clinical findings from 5 guidelines and 21 systematic
      reviews on psoriasis published or indexed in the period November 2009 to October
      2010. The highlights include the British Association of Dermatologists guidelines
      on the use of biological interventions in psoriasis, and guidelines on the
      efficacy and use of acitretin. Biological therapies were reviewed for use in
      specific patient groups (such as those with hepatitis C) and from a health
      economics perspective. Another systematic review focused on outcome measures used
      to assess the severity of psoriasis. Finally, comorbidities including
      cardiovascular risk were the topic of four systematic reviews.

PMID- 21718346
TI  - Genetic analysis of the Alteromonas macleodii [NiFe]-hydrogenase.
AB  - Alteromonas macleodii Deep ecotype is a marine, heterotrophic,
      gammaproteobacterium isolated in the Mediterranean Sea between depths of 1000 and
      3500 m. The sequenced strain was previously reported to contain a [NiFe]
      hydrogenase. We verified the presence of this hydrogenase in other strains of A.
      macleodii Deep ecotype that were previously isolated from several bathypelagic
      microenvironments. We developed a system for the genetic manipulation of A.
      macleodii Deep ecotype using conjugation and used this system to create mutant
      strains that lack the [NiFe] hydrogenase structural genes (hynSL). The mutants
      did not possess hydrogenase activity, and complementation of the mutant strain
      with the hynSL genes successfully restored hydrogenase activity. Both the mutant
      and the wild-type strains grew at the same rate in a variety of media and under
      different environmental conditions, indicating little effect of the hydrogenase
      mutation under the conditions tested.

PMID- 21718347
TI  - Dimethylsulfide is an energy source for the heterotrophic marine bacterium
      Sagittula stellata.
AB  - Dimethylsulfide (DMS) is a volatile organosulfur compound, ubiquitous in the
      oceans, that has been credited with various roles in biogeochemical cycling and
      in climate control. Various oceanic sinks of DMS are known - both chemical and
      biological - although they are poorly understood. In addition to the utilization
      of DMS as a carbon or a sulfur source, some Bacteria are known to oxidize it to
      dimethylsulfoxide (DMSO). Sagittula stellata is a heterotrophic member of the
      Alphaproteobacteria found in marine environments. It has been shown to oxidize
      DMS during heterotrophic growth on sugars, but the reasons for and the mechanisms
      of this oxidation have not been investigated. Here, we show that the oxidation of
      DMS to DMSO is coupled to ATP synthesis in S. stellata and that DMS acts as an
      energy source during chemoorganoheterotrophic growth of the organism on fructose
      and on succinate. DMS dehydrogenase (which is responsible for the oxidation of
      DMS to DMSO in other marine Bacteria) and DMSO reductase activities were absent
      from cells grown in the presence of DMS, indicating an alternative route of DMS
      oxidation in this organism.

PMID- 21718348
TI  - Expression of tmRNA in mycobacteria is increased by antimicrobial agents that
      target the ribosome.
AB  - The specialized RNA, tmRNA, is a central component of prokaryote trans
      translation; a process that salvages stalled translational complexes. Evidence
      from other bacteria suggested that exposure to ribosome inhibitors elevated tmRNA
      levels, although it was unclear whether such changes resulted from increased
      tmRNA synthesis. Consequently, this study was initiated to determine the effect
      of ribosome inhibitors on the expression of tmRNA in mycobacteria. Exposure of
      Mycobacterium smegmatis to ribosome-targeting antimicrobial agents was associated
      with increased levels of the tmRNA precursor, pre-tmRNA, and mature tmRNA. For
      example, exposure to 16 MUg mL-1 erythromycin for 3 h increased pre-tmRNA and
      tmRNA by 18- and 6-fold, respectively. Equivalent results were found following
      exposure of Mycobacterium bovis BCG to streptomycin. Exposure to antimicrobial
      agents with nonribosome targets did not affect tmRNA levels. The increased tmRNA
      levels were associated with increased output from the ssrA promoter, which
      controls tmRNA transcription, without evidence of a change in tmRNA degradation.
      These results suggest that the upregulation of tmRNA expression was an important
      response of bacteria to exposure to ribosome-inhibiting antimicrobial agents.

PMID- 21718349
TI  - Tooth loss and dental caries in community-dwelling older adults in northern
      Manhattan.
AB  - OBJECTIVE: To examine tooth loss and dental caries by sociodemographic
      characteristics from community-based oral health examinations conducted by
      dentists in northern Manhattan. BACKGROUND: The ElderSmile programme of the
      Columbia University College of Dental Medicine serves older adults with varying
      functional capacities across settings. This report is focused on relatively
      mobile, socially engaged participants who live in the impoverished communities of
      Harlem and Washington Heights/Inwood in northern Manhattan, New York City.
      MATERIALS AND METHODS: Self-reported sociodemographic characteristics and health
      and health care information were provided by community-dwelling ElderSmile
      participants aged 65 years and older who took part in community-based oral health
      education and completed a screening questionnaire. Oral health examinations were
      conducted by trained dentists in partnering prevention centres among ElderSmile
      participants who agreed to be clinically screened (90.8%). RESULTS: The dental
      caries experience of ElderSmile participants varied significantly by
      sociodemographic predictors and smoking history. After adjustment in a
      multivariable logistic regression model, older age, non-Hispanic Black and
      Hispanic race/ethnicity, and a history of current or former smoking were
      important predictors of edentulism. CONCLUSION: Provision of oral health
      screenings in community-based settings may result in opportunities to intervene
      before oral disease is severe, leading to improved oral health for older adults.

PMID- 21718350
TI  - Late infective endocarditis of an atrial septal occluder device presenting as a
      cystic mass.
AB  - We report an atypical echocardiographic presentation of a vegetation in a patient
      with late infective endocarditis of an atrial septal defect (ASD) occluder
      device. Transesophageal echocardiography demonstrated a penduculated mass
      attached to the left atrial side of the occluder device. This mass presented as
      an oscillating echo free area surrounded by a membrane attached to the device by
      a thin stalk. At time of surgical excision, the lesion did not present as a
      spherical cyst. It was assumed that the content of the echo free mass had already
      emptied into the left atrium. Histopathology diagnosed the mass as a vegetation.
      The contribution of contrast echocardiography to the evaluation of intracardiac
      masses is briefly discussed.

PMID- 21718351
TI  - Noninvasive assessment of left ventricular end-diastolic pressure with tissue
      Doppler imaging in patients with mitral regurgitation.
AB  - BACKGROUND: The ratio of early transmitral flow velocity to mitral annulus early
      diastolic velocity (E/Ea) is a widely used noninvasive tool to estimate left
      ventricular end diastolic pressure (LVEDP). The aim of this study was to explore
      whether E/Ea ratio was a reliable index for the estimation of LVEDP in patients
      with mitral regurgitation (MR). METHODS: Sixteen patients with nonischemic MR
      (primary MR group; 6 male, 58 +/- 12 years) 51 patients with ischemic MR
      (secondary MR group; 29 male, 63 +/- 9 years) and 29 patients without MR (control
      group; 19 male, 53 +/- 10 years) were consecutively included. The peak
      transmitral flow and mitral annular velocities during early diastole were
      measured. LVEDP was determined invasively by left heart catheterization. RESULTS:
      Primary and secondary MR groups had significantly higher E/Ea ratios and LVEDP
      than control group. LVEDP significantly correlated with E/Ea ratio in patients
      with primary MR, but not in patients with secondary MR. Multiple regression
      analysis revealed that E/Ea ratio was an independent predictor of LVEDP in
      patients with primary MR. Ten patients with primary MR had LVEDP >=15 mmHg. ROC
      analysis demonstrated cutoff values for E/Ea ratios as >10.5 for lateral mitral
      annulus (sensitivity: 80%, specificity: 66%, PPV: 80%, NPV: 66%) and as >14 for
      medial mitral annulus (sensitivity: 90%, specificity: 83%, PPV: 90%, NPV: 83%) to
      predict primary MR patients with LVEDP >=15 mmHg. CONCLUSION: E/Ea ratio is still
      reliable in estimation of LVEDP in primary MR patients while it is not predictive
      for LVEDP in secondary MR patients.

PMID- 21718352
TI  - A study of the 16-Segment Regional Wall Motion Scoring Index and biplane
      Simpson's rule for the calculation of left ventricular ejection fraction: a
      comparison with cardiac magnetic resonance imaging.
AB  - AIMS: Accurate calculation of left ventricular ejection fraction (LVEF) is
      important for diagnostic, prognostic and therapeutic reasons. Cardiac magnetic
      resonance (CMR) is the reference standard for LVEF calculation, followed by real
      time three-dimensional echocardiography (RT3DE). Limited availability of CMR and
      RT3DE leaves Simpson's rule as the two-dimensional echocardiography (2DE)
      standard by which LVEF is calculated. We investigated the accuracy of the 16
      Segment Regional Wall Motion Score Index (RWMSI) as an alternative method for
      calculating LVEF by 2DE and compared this to Simpson's rule and CMR. METHODS AND
      RESULTS: The 2D echocardiograms of 110 patients were studied (LVEF range: 7-74%);
      57 of these underwent CMR. A RWMS was applied, based on the consensus opinion of
      two experienced cardiologists, to each of 16 American Heart Association
      myocardial segments (RWMSI: hyperkinesis = 3; normal regional contraction = 2;
      mild hypokinesis = 1.25; severe hypokinesis = 0.75; akinesis = 0; dyskinesis =
      1). LVEF was calculated by: LVEF(%) =Sigma(16segRWMS)/16*30. LVEF was calculated
      by Simpson's rule and CMR using standard methods. Results were correlated against
      CMR. Intertechnique agreement was examined. A P value of<0.05 was considered
      significant. RWMSI-LVEF correlated strongly with Biplane Simpson's rule (P<
      0.001, r = 0.915). RWMSI-LVEF had a strong correlation to CMR (P < 0.001, r =
      0.916); Simpson's rule-LVEF had a moderate correlation to CMR (P< 0.001, r =
      0.647). In patients with LV dysfunction (EF < 55%), on linear regression
      analysis, RWMSI-LVEF had a better correlation with CMR than Simpson's rule.
      Further more Simpson's rule overestimated LVEF compared to CMR (mean difference: 
      6.12 +/- 16.44, P = 0.002) whereas RWMSI did not (mean difference: 2.58 +/-
      14.80, P = NS). CONCLUSION: RWMSI-LVEF correlates strongly with CMR with good
      intertechnique agreement. In centers where CMR and RT3DE are not readily
      available, the use by experienced individuals, of the RWMSI for calculating LVEF
      may be a more simple, accurate, and reliable alternative to Simpson's rule.

PMID- 21718353
TI  - Real time three-dimensional stress echocardiography: a new approach for assessing
      diastolic function.
AB  - OBJECTIVE: To assess the feasibility of utilizing real time three-dimensional
      echocardiography (RT3DE) for assessment of diastolic function during stress.
      METHODS: Rest and stress volumes were acquired in 24 patients and parameters of
      diastolic function-peak ventricular filling rate (PFR) and time to peak filling
      rate (TPFR)-were calculated. RESULTS: Calculation of diastolic parameters was
      feasible in all patients. Resting PFR correlated with end-diastolic (EDV) and
      stroke volumes and inversely with TPFR (r = 0.53, 0.66, -0.5). With stress, PFR
      increased by 93% and TPFR decreased by 23% (P < 0.001). Stress PFR correlated
      with stress heart rate, EDV and stroke volume (r = 0.52, 0.50, 0.62) while TPFR
      correlated inversely with heart rate (r =-0.71). The change in PFR with stress
      correlated with the change in stroke volume (r = 0.42), while the change in TPFR
      correlated with the change in end-systolic volume (ESV) (r = 0.43) and inversely
      with the change in diastolic blood pressure (r =-0.41). Rest and stress PFR and
      TPFR are independent of age, gender and blood pressure and the change in PFR is
      independent of stress heart rate or blood pressure. E/E' correlated with stress
      TPFR (r = 0.72) and change in TPFR (r = 0.67) and inversely with change in PFR (r
      =-0.67). CONCLUSIONS: RT3DE can assess diastolic function during stress by
      detecting changes in PFR and TPFR, independent of gender, age, and blood
      pressure. The changes in these parameters with stress are influenced by baseline
      filling pressures. Larger studies are required to validate the clinical
      significance of these observations.

PMID- 21718354
TI  - Thrombus entrapped in a patent foramen ovale with pulmonary and systemic
      embolism.

PMID- 21718355
TI  - The incremental value of regional dyssynchrony in determining functional mitral
      regurgitation beyond left ventricular geometry after narrow QRS anterior
      myocardial infarction: a real time three-dimensional echocardiography study.
AB  - BACKGROUND: Determinants of functional mitral regurgitation (FMR) severity after
      acute anterior myocardial infarction (MI) remained unclear. Our aim was to: (1)
      test whether LV dyssynchrony upon real time three-dimensional echocardiography
      (RT-3DE) is independently associated with FMR severity; and (2) to investigate
      the role of regional systolic dyssynchrony index (SDI) in identifying FMR
      severity. METHODS: RT-3DE was successfully performed on 64 consecutive patients
      following acute anterior MI with a narrow QRS complex (<130 ms) and another 30
      healthy volunteers. MR severity was assessed using vena contracta method. SDI was
      derived from the dispersion of the time to minimum regional volume for all 16 LV
      segments. Multiple linear regression analysis was used to identify the
      independent relationship between FMR and SDI with and without multivariate
      adjustment. RESULTS: The mean LV ejection fraction was 49.6%+/- 11.9% in the MI
      group. All regional (except apical) and global SDIs were associated with regional
      LV remodeling and were significantly correlated with FMR even after multivariate
      adjustment, with midwall SDI being most strongly associated with MR severity
      (R(2) = 0.55, P < 0.001). Regional midwall SDI superimposed on LV global geometry
      and mitral leaflet deformation substantially expanded the area under curve in
      identifying FMR (AUC increased from 0.69 to 0.93, c-statistics: P = 0.041).
      CONCLUSIONS: While both global and regional dyssynchrony following anterior MI
      were independently related to FMR severity, regional midwall dyssynchrony further
      added incremental value in predicting FMR severity beyond traditional parameters.
      This finding provides a new insight into the understanding of FMR after anterior
      MI and may further potentiate specific therapeutic approaches.

PMID- 21718356
TI  - The effect of different atrioventricular delays on left atrium and left atrial
      appendage function in patients with DDD pacemaker.
AB  - BACKGROUND: Although it has been known that optimization of atrioventricular
      delay (AVD) has favorable effect on the left ventricular functions in patients
      with DDD pacemaker, the effect of different AVDs on left atrium (LA) and left
      atrial appendage (LAA) functions has not been exactly evaluated. The aim of the
      present study was to assess the effect of different AVDs on LA and LAA functions
      in DDD pacemaker implanted patients with atrioventricular block. METHODS: Forty
      eight patients with DDD pacemaker were enrolled into the study. Patients were
      divided into two groups according to the echocardiographic diastolic function:
      Group I (normal diastolic function) and Group II (diastolic dysfunction). LAA
      emptying velocity on pulsed wave Doppler and LAA late systolic wave velocity by
      using tissue Doppler were recorded. Patients were paced for five successive
      continuous pacing periods of 10 minutes duration using five selective AVDs (80
      250 ms). RESULTS: Significant effect on LA and LAA functions has not been
      observed by the setting of AVD in Group I. However, when the AVD was gradually
      shortened form 150 ms to 80 ms, LA and LAA functions gradually decreased in Group
      II patients. When AVD increased to 200 ms, LA and LAA functions were improved.
      Further increase in AVD resulted in decreased LA and LAA functions. CONCLUSION:
      Setting of AVD has not significant effect on the LA and LAA functions in patients
      with normal diastolic function, but moderate prolongation of AVD in physiological
      limits improved LA and LAA functions in DDD pacemaker implanted patients with
      diastolic dysfunction.

PMID- 21718357
TI  - The origin and clinical significance of the signal opposite to the mitral E-wave:
      a simple and novel indicator of left ventricular filling pressure.
AB  - OBJECTIVES: We noted a low-velocity signal opposite to the early diastolic
      transmitral flow (E) by pulsed Doppler echocardiography. The purpose of this
      study was to examine the origin and significance of this signal. BACKGROUND: The
      background of the signal remains uncertain. METHODS: We studied 59 adult patients
      (34 men and 25 women; mean age, 58.9 [20.2] years) without mitral valve heart
      disease. Mitral E-wave velocity and the signal (EW) opposite the E-wave were
      measured by pulsed Doppler echocardiography. Early diastolic mitral valve ring
      motion velocity (Ea) was measured by pulsed tissue Doppler echocardiography.
      Pulmonary capillary wedge pressure (PCWP) was measured by a Swan-Ganz catheter in
      34 of the 59 patients. RESULTS: A blue signal was observed during early diastole
      from the mitral valve ring to the mitral orifice areas by color tissue Doppler
      echocardiography. The velocity profile method revealed the same direction and
      time between peak Ea and EW. Peak EW positively correlated with Ea (r = 0.67, P <
      0.01). There were significant positive correlations between mean PCWP and E/Ea (r
      = 0.61, P < 0.01) and E/EW (r = 0.59, P < 0.01). E/EW was significantly greater
      in patients with PCWP > 12 mmHg than in patients with PCWP <= 12 mmHg (5.6 [1.3]
      cm/s vs. 4.3 [0.9] cm/s, P < 0.01). CONCLUSIONS: EW may be related to mitral
      valve ring motion, and the E/EW ratio may be a noninvasive simple parameter for
      assessing left ventricular filling pressure.

PMID- 21718358
TI  - Two risk score models for predicting incident Type 2 diabetes in Japan.
AB  - AIMS: Risk scoring methods are effective for identifying persons at high risk of
      Type 2 diabetes mellitus, but such approaches have not yet been established in
      Japan. METHODS: A total of 1935 subjects of a derivation cohort were followed up
      for 14 years from 1988 and 1147 subjects of a validation cohort independent of
      the derivation cohort were followed up for 5 years from 2002. Risk scores were
      estimated based on the coefficients (beta) of Cox proportional hazards model in
      the derivation cohort and were verified in the validation cohort. RESULTS: In the
      derivation cohort, the non-invasive risk model was established using significant
      risk factors; namely, age, sex, family history of diabetes, abdominal
      circumference, body mass index, hypertension, regular exercise and current
      smoking. We also created another scoring risk model by adding fasting plasma
      glucose levels to the non-invasive model (plus-fasting plasma glucose model). The
      area under the curve of the non-invasive model was 0.700 and it increased
      significantly to 0.772 (P < 0.001) in the plus-fasting plasma glucose model. The
      ability of the non-invasive model to predict Type 2 diabetes was comparable with
      that of impaired glucose tolerance, and the plus-fasting plasma glucose model was
      superior to it. The cumulative incidence of Type 2 diabetes was significantly
      increased with elevating quintiles of the sum scores of both models in the
      validation cohort (P for trend < 0.001). CONCLUSIONS: We developed two practical
      risk score models for easily identifying individuals at high risk of incident
      Type 2 diabetes without an oral glucose tolerance test in the Japanese
      population.

PMID- 21718359
TI  - Identification of two arylalkylamine N-acetyltranferase 1 genes with different
      developmental expression profiles in the flatfish Solea senegalensis.
AB  - The existence of two arylalkylamine N-acetyltransferase 1 (Aanat1) genes in the
      genome of some teleosts has been reported recently by in silico analysis.
      However, there are no data concerning the similarities and/or differences between
      them and many questions remain to be answered, such as their expression sites,
      development, or kinetics. Here, we report the cloning of Aanat1a and Aanat1b
      cDNAs from the sole retina and show for the first time that at least three Aanat
      genes are expressed in a vertebrate species. Because melatonin is involved in
      fish ontogeny, we analyzed the developmental transcript levels of Aanat1a and
      Aanat1b by quantitative real-time PCR, showing their inverse and stage-specific
      expression patterns. Aanat1a was more abundant during early than late larval
      stages. Before metamorphosis, nocturnal expression was higher. At metamorphosis,
      Aanat1a expression decreased and lost these day-night variations. In contrast,
      the abundance of Aanat1b transcripts, low during early developing stages, rose
      significantly throughout metamorphosis. This situation seemed to apply to the
      adult because Aanat1a expression was lower than Aanat1b expression in the retina
      of adults, where the former did not exhibit day-night variations, while the
      latter did so with much higher nocturnal transcript levels. In situ hybridization
      analysis detected Aanat1a and Aanat1b messengers in the outer and inner nuclear
      layers of retina. The differences in abundance and distinct day-night expression
      patterns between Aanat1a and Aanat1b during sole development suggest different
      functions for these two enzymes as well as the existence of interactions between
      the melatoninergic and thyroid hormone systems during flatfish metamorphosis.

PMID- 21718360
TI  - Melatonin prolongs graft survival of pancreas allotransplants in pigs.
AB  - Oxidative stress is involved in ischemia-reperfusion injury and allograft
      rejection after transplantation. We studied two well-known antioxidants,
      melatonin and ascorbic acid (AA), in relation to the survival of a pancreas
      transplantation model without immunosuppression. Forty-eight Landrace pigs were
      divided into three groups (n = 16 each; eight donors and eight recipients) that
      received melatonin, AA, or no antioxidant therapy (controls). Melatonin and AA
      were administered (10 mg/kg body weight) intravenously to donors and recipients
      during surgery and on postoperative days 1-7. The molecules were also added (5
      mm) to a University of Wisconsin preservation solution during organ cold storage.
      Melatonin significantly delayed acute rejection and prolonged allograft survival
      (25.1 +/- 7.7 days) compared with the controls (8.1 +/- 0.8 days, P = 0.013) and
      the AA group (9.4 +/- 1.6 days, P = 0.049). Melatonin reduced indicators of
      oxidative stress, malondialdehyde, and 4-hydroxyalkenals, in pancreatic samples
      collected during procurement, cold ischemia, and reperfusion. Melatonin also
      reduced serum pig-major acute-phase protein/inter-alpha-trypsin inhibitor heavy
      chain 4 (pMAP/ITIH(4)) in the early post-transplantation period. AA only
      partially reduced oxidative damage 30 min postreperfusion and failed to prevent
      pMAP/ITIH(4) elevations. These findings suggested that melatonin may be a useful
      therapeutic tool for organ transplantation.

PMID- 21718361
TI  - Melatonin modulation of intracellular signaling pathways in hepatocarcinoma HepG2
      cell line: role of the MT1 receptor.
AB  - Melatonin reduces proliferation in many different cancer cell lines. However,
      studies on the oncostatic effects of melatonin in hepatocarcinoma are limited. We
      have previously demonstrated that melatonin administration induces cycle arrest,
      apoptosis, and changes in the expression of its specific receptors in HepG2 human
      hepatocarcinoma cells. In this study, we used the receptor antagonist luzindole
      to assess the contribution of MT1 melatonin membrane receptor to melatonin
      effects on cell viability, mitogen-activated protein kinase (MAPKs) activation,
      and cAMP levels. Additionally, effects of MT1 inhibition on mRNA levels of
      cytosolic quinone reductase type-2 (NQO2) receptor and nuclear retinoic acid
      related orphan receptor alpha (RORalpha) were tested. Melatonin, at 1000 and 2500
      MUm, significantly reduced cell viability. Pre-incubation with luzindole
      partially inhibited the effects of melatonin on cell viability. Melatonin at 2500
      MUm significantly reduced cAMP levels, and this effect was partially blocked by
      luzindole. Both melatonin concentrations increased the expression of
      phosphorylated p38, ERK, and JNK. ERK activation was completely abolished in the
      presence of luzindole. NQO2 but not RORalpha mRNA level significantly increased
      in luzindole-treated cells. Results obtained provide evidence that the melatonin
      effects on cell viability and proliferation in HepG2 cells are partially mediated
      through the MT1 membrane receptor, which seems to be related also with melatonin
      modulation of cAMP and ERK activation. This study also highlights a possible
      interplay between MT1 and NQO2 melatonin receptors in liver cancer cells.

PMID- 21718362
TI  - Melatonin promotes differentiation of 3T3-L1 fibroblasts.
AB  - Melatonin inhibits the genesis and growth of breast cancer by interfering at
      different levels in the estrogen-signaling pathways. Melatonin inhibits aromatase
      activity and expression in human breast cancer cells, thus behaving as a
      selective estrogen enzyme modulator. As the adipose tissue adjacent to the tumor
      seems to account for most aromatase expression and enzyme activity in breast
      tumors and also mediates the desmoplastic reaction or accumulation of
      undifferentiated fibroblasts around malignant epithelial cells, in this work, we
      studied the effects of melatonin on the conversion of preadipocytes (3T3-L1) into
      adipocytes and on the capability of these cells to synthesize estrogens by
      regulating the expression and enzyme activity of aromatase, one of the main
      enzymes that participates in the synthesis of estrogens in the peritumoral
      adipose tissue. Thus, in both differentiating and differentiated 3T3-L1
      adipocytes, high concentrations of melatonin increased intracytoplasmic
      triglyceride accumulation, an indicator of adipogenic differentiation. Melatonin
      (1 mm) significantly increased the expression of both CCAAT/enhancer-binding
      protein alpha and peroxisome proliferator-activated receptor gamma, two main
      regulators of terminal adipogenesis, in 3T3-L1 cells. The presence of melatonin
      during differentiation also induced a parallel reduction in aromatase expression
      and activity and expression of the cells. The effects of melatonin were reversed
      by luzindole, a melatonin receptor antagonist, indicating that melatonin acts
      through known receptor-mediated mechanisms. These findings suggest that, in human
      breast tumors, melatonin could stimulate the differentiation of fibroblasts and
      reduce the aromatase activity and expression in both fibroblasts and adipocytes,
      thereby reducing the number of estrogen-producing cells proximal to malignant
      cells.

PMID- 21718363
TI  - Melatonin improves D-galactose-induced aging effects on behavior, neurogenesis,
      and lipid peroxidation in the mouse dentate gyrus via increasing pCREB
      expression.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) has multiple functions. In this study,
      we investigated the effects of melatonin on memory, cell proliferation, and
      neuroblast differentiation in the dentate gyrus of a mouse model of D-galactose
      induced aging. D-galactose was subcutaneously administered to 7-wk-old mice for
      10 wk, and age-matched mice were used as controls. Seven weeks after D-galactose
      administration, vehicle (water) or melatonin (6 mg/L in water) was administered
      ad libitum to the mice for 3 wk. The administration of D-galactose significantly
      increased the escape latency compared with that in the control mice on days 1-3.
      In addition, cells in the subgranular zone and in the granule cell layer of the
      dentate gyrus showed severe damage (cytoplasmic condensation) in the D-galactose
      treated mice. However, melatonin supplementation to these mice for 3 wk
      significantly ameliorated the D-galactose-induced increase in escape latency and
      neuronal damage compared with the vehicle-treated group. The administration of
      melatonin also significantly restored the D-galactose-induced reduction of
      proliferating cells (Ki67-positive cells) and differentiating neuroblasts
      (doublecortin-positive neuroblasts) in the dentate gyrus. Furthermore, the
      administration of melatonin significantly increased Ser133-phosphorylated cyclic
      AMP response element binding protein in the dentate gyrus. The administration of
      melatonin significantly reduced D-galactose-induced lipid peroxidation in the
      dentate gyrus. These results suggest that melatonin may be helpful in reducing
      age-related phenomena in the brain.

PMID- 21718364
TI  - Effects of respiratory mechanical forces on the pharmacological response of lung
      cancer cells to chemotherapeutic agents.
AB  - In vitro screening of chemotherapeutic agents is routinely carried out in static
      monolayer cell cultures. However, drugs administered to patients act in the
      presence of various microenvironments in vivo. For example, in lung tumors,
      mechanical forces are constantly present and do affect the physiological response
      of the lung tissue to a variety of therapeutic agents. We hypothesized that
      mechanical forces may affect the response of lung tumors to chemotherapeutic
      agents and studied the effects under simulated conditions. First, we examined the
      effects of simulated forces that approximate normal respiration on the
      proliferation and morphology of NCI-H358 and A549 cell lines. Then, we studied
      the effects of the simulated forces on the ability of Paclitaxel, Doxorubicin,
      Cisplatin, Zactima and an experimental drug to induce cytotoxicity in both cell
      lines. Cells were treated with the drugs in the presence or absence of simulated
      forces (20% maximum strain and 15 cycles/minute) that approximate human lung
      expansion and contraction. Cell proliferation and the effectiveness of the drugs
      were assessed. Using a standard exponential cell growth model, it was determined
      that mechanical forces significantly reduced the proliferation of both cell
      lines. Interestingly, forces also significantly lowered the effectiveness of all
      drugs except Zactima in A549 cells, while in NCI-H358 cells, Zactima was the only
      drug that demonstrated an increase in effectiveness owing to applied forces. Our
      results demonstrate that mechanical forces have significant impact on cell
      survival and chemotherapeutic efficacy and may be of significance in engineering
      improved screening assays for antitumor drug discovery.

PMID- 21718365
TI  - Transient blood eosinophilia during treatment with Adalimumab.

PMID- 21718366
TI  - Autoimmune markers in vitiligo patients appear correlated with obsession and
      phobia.
AB  - BACKGROUND: Current studies have treated a limited portion of the subjective
      aspects of vitiligo patients and have yet to elucidate possible psychological
      differences between those with autoimmune markers (AIM) with respect to those
      without autoimmune markers (NAIM). OBJECTIVE: To perform an age and gender
      matched 1:1 case-control study through a comparison of non-segmental vitiligo
      patients with autoimmune features vs. those without autoimmune features in
      regards to psychiatric features, psychosomatic aspects and social parameters.
      METHODS: A total of 112 non-segmental vitiligo patients have been examined at the
      Florence University dermatology outpatient service (2nd dermatology unit).
      Vitiligo with an autoimmune background was defined by the presence of autoimmune
      antibodies and/or autoimmune diseases. Psychiatric screening was performed by
      dermatologists using the modified Middlesex Healthcare Questionnaire (MHQ);
      psychosomatic aspects and social impact were analysed with a standardized,
      Florentine questionnaire. RESULTS: Upon performing a conditional regression
      model, age, phobia and obsession were significantly predictive of the presence of
      AIM and a low total MHQ score was significantly predictive of NAIM in vitiligo
      patients. With univariate analysis, we found significant differences in:
      identifiable stress related to the onset of vitiligo, vitiligo triggered by
      stress, and modified interpersonal relationships related to vitiligo, which were
      associated with the subgroup containing autoimmunity markers. CONCLUSIONS: We
      found a higher prevalence of age, obsession and phobia among vitiligo patients
      AIM as compared to vitiligo patients NAIM. Thus, in the presence of demonstrated
      autoimmunity, screening for particular psychiatric aspects may be useful in the
      clinical practice of vitiligo.

PMID- 21718367
TI  - Increased HAS2-driven hyaluronic acid synthesis in shar-pei dogs with hereditary
      cutaneous hyaluronosis (mucinosis).
AB  - The Chinese shar-pei dog is known for its distinctive feature of wrinkled and
      thickened skin, defined as primary or hereditary cutaneous mucinosis. In a recent
      report, we identified the mucinous material deposited in the shar-pei skin as the
      polysaccharide hyaluronan (HA). In the present work, the molecular and cellular
      mechanisms underlying this phenotype have been identified in dermal fibroblasts
      isolated from shar-pei dogs. The production of HA, which appeared to be mainly
      associated with cell membrane protrusions and also intracellular, was higher in
      shar-pei fibroblasts than in control cells. The HA accumulation is related to a
      higher mRNA expression of the isoform HAS2 of the HA-synthesizing enzyme family,
      hyaluronan synthases (HAS). The higher expression of HAS2 in shar-pei fibroblasts
      was confirmed at the protein level. The other HAS isoenzymes, HAS1 and HAS3, and
      the HA-degrading enzymes, Hyal1 and Hyal2, were not differentially expressed in
      shar-pei fibroblasts compared with cells from control dogs. Fibroblasts from shar
      pei dogs and from control dogs are morphologically different as observed by
      transmission electron microscopy. Scanning electron microscopy revealed a large
      number of cellular protrusions with associated globular deposits. Electron
      microscopy after labelling with biotinylated HA-binding protein confirmed an
      increased HA content in shar-pei fibroblasts, which could be localized in several
      subcellular structures. The authors propose the name hereditary cutaneous
      hyaluronosis (HCH) for affected dogs, because it better defines the cutaneous
      mucinosis of shar-pei dogs.

PMID- 21718368
TI  - Comparable efficacy of a topical 0.0584% hydrocortisone aceponate spray and oral
      ciclosporin in treating canine atopic dermatitis.
AB  - This study compared the efficacy of a 0.0584% hydrocortisone aceponate (HCA)
      spray (Cortavance((r)); Virbac SA) and ciclosporin (Atopica((r)); Novartis Animal
      Health) in canine atopic dermatitis in a single-blind randomized controlled
      trial. Dogs received HCA (two sprays/100 cm(2); n=24) or ciclosporin (5 mg/kg;
      n=21). Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03, pruritus
      (visual analog scale with grade descriptors) and owner scores (5-point scales)
      were recorded every 28 days for 84 days. Intention-to-treat data were analysed.
      CADESI-03 and pruritus significantly decreased over time (P<0.0001), but there
      was no difference between the treatment groups (P=0.91 and P=0.52, respectively).
      Similar proportions of HCA- and ciclosporin-treated dogs achieved >=50%
      reductions in CADESI-03 and pruritus scores at 28 days (CADESI-03 58.3 and 57.1%,
      P=0.76; pruritus 33.3 and 38.1%, P=1.0), 56 days (CADESI-03 70.8 and 81.0%,
      P=1.0; pruritus 62.5 and 57.1%, P=1.0) and 84 days (CADESI-03 75 and 85.7%,
      P=0.72; pruritus 65.2 and 57.1%, P=0.76). The CADESI-03 and pruritus scores were
      close to equivalence (0.47 and 0.51, respectively). By 84 days, every-other-day
      or twice-weekly therapy was achieved in 13 of 24 HCA- and 12 of 21 ciclosporin
      treated dogs (P=0.85). There were no significant differences in scores for
      efficacy (P=0.82), tolerance (P=0.62) and ease of administration (P=0.25). Scores
      for tolerance (0.49) and administration (0.46) were close to equivalence. The
      score for efficacy favoured HCA (0.68). Mild adverse events were noted in six of
      21 ciclosporin and none of 24 HCA dogs (P=0.008). Five HCA-treated dogs and three
      ciclosporin-treated dogs were prematurely withdrawn (P=0.7). In conclusion, HCA
      and ciclosporin proved equally effective in treating canine atopic dermatitis for
      up to 84 days.

PMID- 21718369
TI  - Efficacy of a 0.0584% hydrocortisone aceponate spray in presumed feline allergic
      dermatitis: an open label pilot study.
AB  - This study evaluated the efficacy of a 0.0584% hydrocortisone aceponate (HCA)
      spray (Cortavance((r)); Virbac SA) in 10 cats with presumed allergic dermatitis.
      The cats initially received two sprays/100 cm(2) of skin once daily. Clinical
      lesions (a Feline Dermatitis Extent and Severity Index; FeDESI), pruritus (10 cm
      visual analog scale with grade descriptors) and owner assessments of efficacy,
      tolerance and ease of use (from 1=very poor to 5=excellent) were assessed every
      14 days. The frequency of treatment was reduced after day 28 in cats with a >50%
      reduction in FeDESI and pruritus scores. One cat was lost to follow up at day 28
      and two at day 42. Intention-to-treat data were analysed. The FeDESI [mean (SD):
      day 0, 42.2 (15.7) and day 56, 9.9 (11.7); P<0.0001] and pruritus scores [day 0,
      61.2 mm (20.1) and day 56, 14.6 mm (16.1); P<0.0001] significantly decreased
      throughout the trial. The owner scores for tolerance [median (range): day 14, 4
      (1-5) and day 56, 4 (3-5); P=0.003] and ease of administration [day 14, 3 (2-5)
      and day 56, 4 (2-5); P=0.02] significantly increased during the trial, but there
      was no significant change in efficacy scores [day 14, 4 (3-5) and day 56, 4 (2
      5); P=0.5]. There were no adverse effects attributable to the HCA spray, no
      significant changes in weight [mean (SD): day 0, 5.0 kg (1.4) and day 56, 5.0 kg
      (1.6); P=0.51] and no significant changes in haematology, biochemistry or
      urinalysis (n=4). Six cats required every-other-day treatment and four required
      daily treatment. In conclusion, HCA spray appeared to be effective and safe in
      these cats, although it is not licensed for use in this species.

PMID- 21718370
TI  - Successful treatment of a novel generalized variant of canine discoid lupus
      erythematosus with oral hydroxychloroquine.
AB  - Discoid lupus erythematosus (DLE) is a common canine autoimmune disease that
      usually manifests as a localized ulcerative and scarring nasal dermatitis. We
      report herein a generalized variant of canine DLE successfully treated with the
      antimalarial immunomodulator hydroxychloroquine (HCQ). A 9-year-old hairless
      Chinese crested dog was presented with annular and polycyclic hyperpigmented and
      scaly skin lesions with central erosions, hypopigmentation and/or scarring on the
      trunk, neck and lateral extremities. Associated systemic signs were not seen. The
      clinical diagnosis of generalized DLE was supported by the demonstration of
      lymphocyte-rich interface dermatitis with epidermal atrophy and dermo-epidermal
      deposition of immunoglobulins and activated complement. As for human DLE,
      treatment was initiated with HCQ at 5 mg/kg once daily along with 2 weeks of 0.1%
      tacrolimus ointment and restriction of sun exposure. Over the following year,
      complete remission was maintained with HCQ at 5 mg/kg orally once daily with the
      exception of three relapses; two occurred during treatment induction and the
      third arose when the frequency of HCQ administration was reduced to every other
      day. Disease flares were controlled with 0.1% tacrolimus ointment alternating
      with 0.1% prednicarbate cream once daily for 5-10 days. Altogether, adverse drug
      events were not seen with this regimen. In summary, clinically, histologically
      and immunologically, this dog's disease mirrored the generalized discoid variant
      of chronic cutaneous lupus erythematosus of humans. The apparent benefit of HCQ,
      its safety and low cost warrant future investigations of its use for treatment of
      canine cutaneous lupus variants.

PMID- 21718371
TI  - Gene expression profiling in male genital lichen sclerosus.
AB  - Male genital lichen sclerosus (MGLSc) has a bimodal distribution in boys and men.
      It is associated with squamous cell carcinoma (SCC). The pathogenesis of MGLSc is
      unknown. HPV and autoimmune mechanisms have been mooted. Anti extracellular
      matrix protein (ECM)1 antibodies have been identified in women with GLSc. The
      gene expression pattern of LSc is unknown. Using DNA microarrays we studied
      differences in gene expression in healthy and diseased prepuces obtained at
      circumcision in adult males with MGLSc (n = 4), paediatric LSc (n = 2) and normal
      healthy paediatric foreskin (n = 4). In adult samples 51 genes with significantly
      increased expression and 87 genes with significantly reduced expression were
      identified; paediatric samples revealed 190 genes with significantly increased
      expression and 148 genes with significantly reduced expression. Concordance of
      expression profiles between adult and paediatric samples indicates the same
      disease process. Functional analysis revealed increased expression in the adult
      and child MGSLc samples in the immune response/cellular defence gene ontology
      (GO) category and reduced expression in other categories including genes related
      to squamous cancer. No specific HPV, autoimmune or squamous carcinogenesis
      associated gene expression patterns were found. ECM1 and CABLES1 expression were
      significantly reduced in paediatric and adult samples respectively.

PMID- 21718372
TI  - Caries prevalence and its association with brushing habits, water availability,
      and the intake of sugared beverages.
AB  - BACKGROUND. With Dental Caries being the most common disease amongst children in
      the world today, there is a need to fully understand risk factors that may be
      related to caries prevalence and how they could be best addressed. AIM. The aim
      of this study was to evaluate soda, juice, sugared-beverage intake, brushing
      habits, and community water source availability as they relate to the prevalence
      of both noncavitated and cavitated caries lesions in small rural villages in
      Mexico. DESIGN. The International Caries Detection and Assessment System (ICDAS)
      was used in children from small, isolated, villages in Mexico. Risk factors were
      assessed via questionnaires. RESULTS. Caries prevalence in the villages was very
      high, ranging from 94.7% to 100% of the children studied. The mean number of
      surfaces with lesions per child (D1MFS + d1mfs) having scores >=1 (noncavitated
      and cavitated) ranged from 15.4 +/- 11.1 to 26.6 +/- 15.2. Many of the children
      reported drinking beverages containing sugar. CONCLUSIONS. Drinking sugared
      beverages, poor oral hygiene habits, and lack of access to tap water were
      identified as risk factor for caries in this sample of residents of rural Mexico.

PMID- 21718373
TI  - Efficacy of a non-drilling approach to manage non-cavitated dentin occlusal
      caries in primary molars: a 12-month randomized controlled clinical trial.
AB  - BACKGROUND. Despite the efficacy of non-drilling approaches to manage non
      cavitated dentin occlusal lesions (NCDOL) in permanent teeth, there is no data
      validating this type of therapy in the primary dentition. AIM. To compare the
      efficacy of a traditional fissure sealant in managing NCDOL in primary molars.
      DESIGN. This study is a randomized controlled clinical trial with a split-mouth
      design. Thirty schoolchildren with two NCDOL were selected and divided into two
      groups. The experimental group received a resin-based fissure sealant, whereas
      the control group was treated with a conventional composite resin. Treatment
      efficacy was evaluated after 1 year by means of clinical and radiographic
      examinations. RESULTS. The two treatment modalities were found to be similarly
      effective in managing DONCL in primary molars. CONCLUSION. For the management of
      non-cavitated dentin occlusal caries in primary teeth, the invasive approach can
      be replaced with non-drilling fissure sealing techniques.

PMID- 21718374
TI  - An estimation and evaluation of total antioxidant capacity of saliva in children
      with severe early childhood caries.
AB  - BACKGROUND. The available evidence implicating the involvement of oxidative
      stress in the caries process suggests that local antioxidant status may be of
      importance in determining the susceptibility to the caries process. AIM. The aim
      of this study was to estimate the total antioxidant capacity (TAC) in
      unstimulated saliva of healthy children with and without severe early childhood
      caries (S-ECC) and to correlate the individual TAC level with dmft (d = decayed,
      m = missing, f = filled, t = teeth) score and age. MATERIAL AND METHODS. The TAC
      of saliva was investigated in 100 healthy children in the age range of 3-5 years
      divided in two groups, control and study group based on the absence or presence
      of caries, respectively. The antioxidant capacity of saliva was estimated by an
      adaptation of ABTS [2, 2'-Azino-di-(3-ethylbenzthiazoline sulphonate)] assay.
      RESULTS. The mean TAC level in the saliva of the children in study group was
      found to be significantly increased (P < 0.001), and a significantly linear
      regression was seen between the TAC and dmft score (P < 0.001) whereas it was
      insignificant between the TAC and age (P = 0.078). CONCLUSION. The results
      indicated that TAC of saliva increased significantly in children with S-ECC and
      increasing prevalence of dental caries predisposes to the increase in TAC of
      saliva.

PMID- 21718375
TI  - Experiences of and influences on continuity of care for service users and carers:
      synthesis of evidence from a research programme.
AB  - Health and social care systems experience difficulty in delivering the continuity
      of care that service users want. Lack of clarity about what continuity means
      hinders service organisation and delivery. The NIHR Service Delivery and
      Organisation programme funded a series of research projects to tackle this
      conceptual confusion, and subsequently commissioned a review of the projects'
      outputs. The aim was to assess how the projects had progressed conceptualisation
      and measurement of continuity, and increased knowledge about what influenced it.
      This paper concentrates on two questions: what is continuity of care, and what
      influences it? We reviewed the projects' outputs and extracted data using
      techniques adapted from systematic reviewing methods. We treated the outputs as
      'transcripts' and used the Framework approach to qualitative analysis to handle
      them. This maintained the coherence of individual projects while allowing cross
      project themes to emerge. We then produced a narrative synthesis of findings.
      Service users and carers valued good relationships with professionals; this did
      not always mean seeing the same person and encompassed trust, the professional's
      style and communication skills, and the time made available. Service users and
      carers also valued understanding the patient's condition and treatment. This went
      beyond giving information, to include communication that recognised individuals'
      capacities and that was skilled, given sufficient time, and from a trusted
      source. Service users valued co-ordination between professionals and services;
      this covered communication, planning, and services' storage and use of
      information about them. Co-ordination with carers and others was also important.
      Experiences of continuity were influenced by service users' characteristics and
      circumstances, care trajectories, the structure and administration of services,
      professionals' characteristics, carer participation, the wider context of the
      'whole person' and satisfaction. The review highlighted how service users, carers
      and professionals construct continuity dynamically between themselves. This has
      implications for both professional training and service users' expectations.

PMID- 21718376
TI  - Quality of life in older outpatients living alone in the community in Italy.
AB  - There is limited knowledge on the relationship between the living conditions of
      community-dwelling older people and their quality of life (QOL) considered in all
      its specific domains. The purpose of this study was to determine (1) which
      dimensions of QOL were independently associated with living alone and (2) the
      independent correlates of these dimensions of QOL amongst older outpatients. We
      conducted a cross-sectional survey of 239 community-dwelling outpatients aged 65+
      (mean age 81.5 years) consecutively referred to a geriatric medicine clinic in
      Italy between June and November 2009 (response rate 93%). Subjects underwent a
      comprehensive geriatric assessment including QOL, which was evaluated by using
      the Older People's QOL questionnaire. In multivariate logistic regression
      analyses, living alone was associated with the lowest score-based tertile of two
      specific dimensions of QOL out of seven, namely 'social relationships and
      participation' [odds ratio (OR) 2.73, 95% confidence interval (CI) 1.08-6.91] and
      'home and neighbourhood' (OR 4.96, 95% CI 1.75-14.07), independently of the main
      demographic, social, functional and clinical characteristics of the subjects.
      Amongst the 107 subjects living alone, independent correlates of these dimensions
      of QOL were depression, having no caregiver and having never been married.
      Depression, having no caregiver and having never been married could provide a
      valuable means of identifying older people living alone who are at greater risk
      of a poor QOL and who would most benefit from effective social and medical
      interventions.

PMID- 21718377
TI  - Social determinants of older adults' awareness of community support services in
      Hamilton, Ontario.
AB  - Community support services (CSSs) have been developed in Canada and other Western
      nations to enable persons coping with health or social issues to continue to live
      in the community. This study addresses the extent to which awareness of CSSs is
      structured by the social determinants of health. In a telephone interview
      conducted in February-March 2006, 1152 community-dwelling older adults (response
      rate 12.4%) from Hamilton, Ontario, Canada were made to read a series of four
      vignettes and were asked whether they were able to identify a CSS they may turn
      to in that situation. Across the four vignettes, 40% of participants did name a
      CSS as a possible source of assistance. Logistic regression was used to determine
      factors related to awareness of CSSs. Respondents most likely to have awareness
      of CSS include the middle-aged and higher-income groups. Being knowledgeable
      about where to look for information about CSSs, having social support and being a
      member of a club or voluntary organisations are also significant predictors of
      awareness of CSSs. Study results suggest that efforts be made to improve the
      level of awareness and access to CSSs among older adults by targeting their
      social networks as well as their health and social care providers.

PMID- 21718378
TI  - Data interpretation: using probability.

PMID- 21718379
TI  - Predicting the outcome from pediatric cardiopulmonary arrest.

PMID- 21718380
TI  - Response to epidural anesthesia in neonates for pyloromyotomy and accompanying
      editorial.

PMID- 21718381
TI  - Spinal anesthesia is a blessing for children.

PMID- 21718382
TI  - ED50 of levobupivacaine with clonidine: is the starting dose right?

PMID- 21718383
TI  - Rare complications of central venous catheter insertion: the guidewire lodging
      chordae tendinaea of tricuspid valve.

PMID- 21718384
TI  - Anesthetic management of a patient with GAPO syndrome for glaucoma surgery.

PMID- 21718385
TI  - Comment on original article by A.J. Braga and A.E.R. Young (April 2011 issue).
      Preventing venous thrombosis in critically ill children: what is the right
      approach?

PMID- 21718386
TI  - Complement-mediated tumor-specific cell lysis by antibody combinations targeting
      epidermal growth factor receptor (EGFR) and its variant III (EGFRvIII).
AB  - Monoclonal antibodies (mAb) against variant III of epidermal growth factor
      receptor (EGFRvIII) hold promise for improving tumor selectivity of EGFR-targeted
      therapy. Here, we compared Fc-mediated effector functions of three mAb against
      EGFRvIII (MR1-1, ch806, 13.1.2) with those of zalutumumab, a high affinity EGFR
      mAb in advanced clinical trials. MR1-1 and ch806 demonstrated preferential and
      13.1.2 exclusive binding to EGFRvIII, in contrast to zalutumumab, which bound
      both wild-type and EGFRvIII. All four human IgG1kappa mAb mediated antibody
      dependent cellular cytotoxicity (ADCC) of EGFRvIII-expressing cells with
      mononuclear cells and isolated monocytes, while only zalutumumab in addition
      triggered ADCC by polymorphonuclear cells. Interestingly, combinations of
      zalutumumab and EGFRvIII mAb specifically mediated complement-dependent
      cytotoxicity (CDC) of EGFRvIII-transfected but not wild-type cells. Moreover,
      EGFRvIII-specific CDC was significantly enhanced when zalutumumab was combined
      with a Fc-engineered variant of MR1-1 (K326A/E333A). These observations confirm
      the immunotherapeutic potential of antibody combinations against EGFR, and
      demonstrate that tumor selectivity can be improved by combining therapeutic EGFR
      mAb with an antibody against EGFRvIII.

PMID- 21718387
TI  - Development of membrane type-1 matrix  metalloproteinase-specific activatable
      fluorescent  probe for malignant tumor detection.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease that activates
      pro-MMP-2 and pro-MMP13, which are related to tumor malignancy. Therefore, probes
      that specifically image MT1-MMP would be useful for malignant tumor diagnosis. In
      the present study, we prepared rhodamine X-conjugated anti-MT1- MMP antibody
      (anti-MT1-MMP mAb-ROX) as an activatable fluorescent probe and evaluated its
      usefulness for MT1-MMP-specific imaging. Anti-MT1-MMP mAb-ROX was obtained in a
      quenched form with approximately three ROX molecules per mAb. Its fluorescence
      intensity increased approximately 14-fold in the presence of detergent, which is
      suitable for activatable systems. C6 glioma cells and MCF-7 human breast
      adenocarcinoma cells were used as MT1-MMP-positive and MT1-MMP-negative models,
      respectively. The fluorescence intensity of C6 cells treated with anti-MT1-MMP
      mAb-ROX, but not ROX-conjugated isotype control antibody (NC Ab-ROX), increased
      with time and was significantly higher than that of MCF-7 cells at 6 h (P <
      0.001). The fluorescence intensity of cells treated with anti-MT1-MMP mAb-ROX was
      also suppressed by pre-treatment with a MT1-MMP endocytosis inhibitor (P < 0.05).
      Furthermore, the probes were intravenously administered to C6 and MCF-7
      xenografted mice. The tumor-to-muscle (T/M) ratio of the anti-MT1-MMP mAb-ROX
      group was 15.1 +/- 3.2 at 48 h and was significantly higher than that of the NC
      Ab-ROX group (T/M ratio = 4.6 +/- 3.0, P < 0.05) in C6 xenografted mice, while
      the T/M ratio of the anti-MT1-MMP mAb-ROX and NC Ab-ROX groups was not different
      in MCF-7 xenografted mice. These findings suggest that anti-MT1-MMP mAb-ROX is a
      promising probe for specifically detecting MT1-MMP-expressing tumors.

PMID- 21718388
TI  - Overexpression of neurone glial-related cell adhesion  molecule is an independent
      predictor of poor  prognosis in advanced colorectal cancer.
AB  - A downstream target of the Wnt pathway, neurone glial-related cell adhesion
      molecule (Nr-CAM) has recently been implicated in human cancer development.
      However, its role in colorectal cancer (CRC) pathobiology and clinical relevance
      remains unknown. In this study, we examined the clinical significance of Nr-CAM
      protein expression in a retrospective series of 428 CRCs using
      immunohistochemistry and tissue microarrays. Cox proportional hazards regression
      was used to calculate hazard ratios (HR) of mortality according to various
      clinicopathological features and molecular markers. All CRC samples were
      immunoreactive for Nr-CAM protein expression, compared to 10 / 245 (4%) matched
      normal tissue (P < 0.0001). Of 428 CRC samples, 97 (23%) showed Nr-CAM
      overexpression, which was significantly associated with nodal (P = 0.012) and
      distant (P = 0.039) metastasis, but not with extent of local invasion or tumor
      size. Additionally, Nr-CAM overexpression was associated with vascular invasion
      (P = 0.0029), p53 expression (P = 0.036), and peritoneal metastasis at diagnosis
      (P = 0.013). In a multivariate model adjusted for other clinicopathological
      predictors of survival, Nr-CAM overexpression correlated with a significant
      increase in disease-specific (HR 1.66; 95% confidence interval 1.11-2.47; P =
      0.014) and overall mortality (HR 1.57; 95% confidence interval 1.07-2.30; P =
      0.023) in advanced but not early stage disease. Notably, 5-fluorouracil-based
      chemotherapy conferred significant survival benefit to patients with tumors
      negative for Nr-CAM overexpression but not to those with Nr-CAM overexpressed
      tumors. In conclusion, Nr-CAM protein expression is upregulated in CRC tissues.
      Nr-CAM overexpression is an independent marker of poor prognosis among advanced
      CRC patients, and is a possible predictive marker for non-beneficence to 5
      fluorouracil- based chemotherapy.

PMID- 21718389
TI  - Pudendal afferent innervation of the guinea pig external anal sphincter.
AB  - BACKGROUND:   Sensory nerves to the external anal sphincter (EAS) contribute to
      mechanisms promoting continence and defecation, yet we know little about their
      function. We investigated the function of pudendal mechanoreceptors to the guinea
      pig EAS. METHODS: Extracellular recordings from pudendal nerve branches to 14 EAS
      preparations, in vitro, were used to characterize extrinsic primary afferent
      nerve endings activated by circumferential distension. KEY RESULTS: All 42
      pudendal nerve afferents were silent under non-distended conditions. Thirty-three
      of 42 afferents had slowly adapting, low-threshold responses to circumferential
      stretch that correlated with stretch length (R(2) = 0.40, P<0.001). Twenty of 20
      slowly adapting afferents reduced firing when stretch was maintained for 60 s
      (P<0.0001). They had low thresholds to von Frey hairs (0.1-0.5mN). Firing
      frequency correlated with degree of compression (R(2) =0.40, P<0.0001). Nine of
      42 afferents had rapidly adapting responses at the onset/offset of isometric
      stretch. During ramp stretch, small vibrations from the stepper motor evoked
      rapid bursts of firing at frequencies up to 200Hz. Instantaneous frequency was
      unrelated to either the rate or degree of stretch. Rapidly adapting units had low
      thresholds (0.1-0.2mN) to von Frey hairs and small punctate mechanotransduction
      sites. Responses to von Frey hair compression were also rapidly adapting, and
      instantaneous frequency was unrelated to the degree of compression. CONCLUSIONS &
      INFERENCES: The EAS has two functional classes of mechanoreceptors: slowly
      adapting low-threshold and rapidly adapting low-threshold mechanoreceptors. These
      two classes of afferents are likely to be involved in the maintenance of
      continence, and the process of defecation.

PMID- 21718390
TI  - Weekly IM interferon beta-1a in multiple sclerosis patients over 50 years of age.
AB  - BACKGROUND: Efficacy and safety data have not previously been compiled for
      intramuscular interferon beta-1a (IM IFNbeta-1a) in patients with multiple
      sclerosis (MS) >= 50 years of age. We investigated the efficacy and safety of IM
      IFNbeta-1a in patients segregated by 50 and 40 years of age in separate meta
      analyses. METHODS: The MS Clinical Research Group Study, the Controlled High-Risk
      Subjects AVONEX((r)) (IM IFNbeta-1a) MS Prevention Study, the IFNbeta-1a European
      Dose-Comparison Study, and a multicenter, open-label antigenicity and safety
      study of human serum albumin-free IM IFNbeta-1a were analyzed. RESULTS: Overall,
      906 patients (68 aged >= 50 years and 838 aged <50 years, or 323 aged >= 40 years
      and 583 aged <40 years) received IM IFNbeta-1a for >= 24 months. At baseline,
      patients >= 50 years had significantly higher Expanded Disability Status Scale
      scores than patients <50 years (3.4 vs. 2.8; P < 0.001), but fewer relapses in
      the three preceding years (2.6 vs. 3.4; P < 0.001); patients >= 40 years and <40
      years exhibited similar differences. After 2 years of treatment, there were no
      significant differences in annualized relapse rate, sustained disability
      progression, time to sustained disability progression, or number of MRI
      identified gadolinium-enhanced lesions between age groups in either analysis. The
      cumulative probability of relapse was significantly lower in patients >= 40 years
      versus patients <40 years (0.601 vs. 0.702; P < 0.001). Adverse event incidence
      did not differ significantly between age groups in either analysis. CONCLUSIONS:
      IM IFNbeta-1a is effective and well tolerated in patients with MS >= 40 and >= 50
      years as well as younger patients.

PMID- 21718391
TI  - Long-term salivary function after conditioning with busulfan, fractionated or
      single-dose TBI.
AB  - OBJECTIVES: Does conditioning with fractionated total body irradiation (fTBI) or
      busulfan (Bu) causes less salivary dysfunction compared with single dose (sTBI)
      after hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: A
      total of 74 adolescents below 13 years of age received allogeneic HSCT and
      conditioning with either: sTBI, fTBI or Bu. The unstimulated (USSR) and
      stimulated (SSSR) whole salivary secretion rates were measured at 15 years of
      age. RESULTS:   Irrespective of conditioning type, there were no significant
      differences in USSR or SSSR between groups. Girls had a significantly lower SSSR,
      0.7 +/- 0.3 ml per min compared with 1.1 +/- 0.4 ml per min in boys (P < 0.001).
      A significant correlation between age at HSCT and SSSR at 15 years of age (P =
      0.02) in children conditioned with sTBI was found as well as an inverse
      correlation between the plasma area under curve (AUC) of Bu and SSSR. In the
      multivariate model, only female sex was significantly correlated with low SSSR at
      15 years of age (OR 3.93, 95% CI 1.21-12.79; P = 0.021). CONCLUSION: No
      differences in long-term whole salivary function after HSCT in adolescents
      receiving conditioning with sTBI, fTBI or Bu were found. Total systemic exposure
      to Bu was negatively correlated with stimulated salivary secretion.

PMID- 21718392
TI  - Diabetes affects statherin expression in human labial glands.
AB  - BACKGROUND AND OBJECTIVE: Salivary statherin, which plays a special role in the
      defense of tooth integrity, is secreted by both major and minor salivary glands.
      A significantly reduced expression of this was recently found in human major
      salivary glands removed from diabetic subjects and was correlated with the high
      incidence of dental diseases occurring in patients with diabetes. In this study,
      we measured the density of gold particles indicating statherin immunoreactivity
      in labial glands to reveal a significant difference between diabetic and non
      diabetic patients. MATERIALS AND METHODS: Surgical samples of labial glands
      obtained from both diabetic and non-diabetic patients were fixed with a
      glutaraldehyde and paraformaldehyde mixture, embedded in Epon, and treated for
      immunogold histochemistry using a polyclonal antibody specific for statherin.
      RESULTS: Statherin immunoreactivity was detected onto small vesicles diffused
      throughout the cytoplasm of serous cells. Statistical analysis revealed that the
      number of stained particles was significantly lower in the samples from diabetic
      subjects than from non-diabetic subjects. CONCLUSIONS: The results indicate that
      diabetes affects statherin secretion in labial glands and support the hypothesis
      that the increased susceptibility to oral diseases associated with diabetes could
      be related with a reduced statherin secretion.

PMID- 21718393
TI  - Three methods for estimating days of hospitalization because of hospital-acquired
      infection: a comparison.
AB  - OBJECTIVES: The objective of this study is to compare the three methods
      internationally used for estimating days of hospitalization attributable to
      hospital infections by applying them to the same population. The methods are: (1)
      unmatched comparison group; (2) matched control method-based; and (3)
      Appropriateness Evaluation Protocol method. A study of the prevalence of
      infections was performed among patients during hospitalization for an ordinary
      single sampling department. The survey was completed within eight working days
      between 15 and 24 October 2007. All patients admitted at least 24 hours to the
      survey day in each department were included in the study, as well as patients
      discharged/transferred to another hospital or department. During the prevalence
      study 621 patients were observed, 70 of which with infection (equal to 11.27%).
      METHOD: The 70 uninfected patients needed for comparison using method 1 were
      selected through a procedure based on propensity score on demographic variables
      and clinical trials of patients. The Shapiro-Wilk test was used to verify the
      normality of quantitative variables. In comparing the three methods Kruskall
      Wallis test was used (alpha = 0.05), while comparisons between pairs of methods
      were performed with the Mann-Whitney test (alpha = 0.017). RESULTS: Estimation
      results of recovery days with infection using the three comparison tests showed
      that there is a statistically significant difference between the three methods (P
      = 0.016) and there is a significant difference between 1 versus 3 (P = 0.013) and
      between 2 and 3 (P = 0.017), whereas between 1 and 2 no difference was found (P =
      0.82). CONCLUSION: In conclusion, the three methods are not showing the same
      estimations and thus may not be exchangeable.

PMID- 21718394
TI  - Unstructured treatment interruption of antiretroviral therapy in clinical
      practice: a systematic review.
AB  - OBJECTIVE: To characterize the frequency, reasons, risk factors, and consequences
      of unstructured anti-retroviral treatment interruptions. METHOD: Systematic
      review. RESULTS: Seventy studies were included. The median proportion of patients
      interrupting treatment was 23% for a median duration of 150 days. The most
      frequently reported reasons for interruptions were drug toxicity, adverse events,
      and side-effects; studies from developing countries additionally cited treatment
      costs and pharmacy stock-outs as concerns. Younger age and injecting drug use was
      a frequently reported risk factor. Other risk factors included CD4 count,
      socioeconomic variables, and pharmacy stock outs. Treatment interruptions
      increased the risk of death, opportunistic infections, virologic failure,
      resistance development, and poor immunological recovery. Proposed interventions
      to minimize interruptions included counseling, mental health services, services
      for women, men, and ethnic minorities. One intervention study found that the use
      of short message service reminders decrease the prevalence of treatment
      interruption from 19% to 10%. Finally, several studies from Africa stressed the
      importance of reliable and free access to medication. CONCLUSION: Treatment
      interruptions are common and contribute to worsening patient outcomes. HIV/AIDS
      programmes should consider assessing their causes and frequency as part of
      routine monitoring. Future research should focus on evaluating interventions to
      address the most frequently reported reasons for interruptions.

PMID- 21718395
TI  - Regular provision of outreach increases acceptance of cataract surgery in South
      India.
AB  - OBJECTIVES: The prevalence of visual loss and blindness from cataract remains
      high in India. Marginalized communities are frequently reached through outreach
      clinics. The aim of this study was to explore the hypothesis that regular
      outreach, held in the same location by the same provider, leads to greater
      acceptance of cataract surgery than outreach clinics that are irregular in terms
      of timing and location. METHODS: The study was integrated into outreach clinics
      run in two districts by Sankara Eye Centre, Coimbatore, Southern India. A semi
      structured questionnaire was administered to patients who had attended outreach
      eye clinics and either accepted or not accepted the offer of cataract surgery.
      RESULTS: Overall acceptance of surgery was high (91.7%), being higher in the
      district with regular outreach (94.6%vs. 82.3%, P < 0.001). A total of 398
      participants (240, 60% acceptors) were interviewed. Acceptors were more likely to
      live in smaller households and in supportive families than non-acceptors who
      lived in larger families which could not provide support and where transport and
      distance were also barriers (P .001). Attending regular outreach and having had
      first eye cataract surgery were independent predictors of acceptance in a
      logistic regression model. CONCLUSION: The findings indicate the importance of
      providers building trust by organizing regular outreach in the same location.
      Previous eye surgery was also a strong predictor of accepting cataract surgery.
      To promote universal access to health care, marginalized rural communities will
      continue to need outreach for some time to come.

PMID- 21718396
TI  - Correlation of rRNA gene amplicon pyrosequencing and bacterial culture for
      microbial compositional analysis of faecal samples from elderly Irish subjects.
AB  - AIMS: The aim of this investigation was to establish the degree of correlation
      between measurements from culture-dependent microbiological techniques and from
      next generation sequencing technologies. METHODS AND RESULTS: Data generated by
      both techniques were collected from faecal samples from 185 elderly Irish people
      involved in the ongoing ELDERMET study (http://eldermet.ucc.ie). The results for
      three groups of intestinal bacteria were compared. Bifidobacterium sp.,
      Lactobacillus sp. and Enterobacteriaceae were enumerated on selective media
      through culture-dependent techniques, whereas proportions of these bacteria were
      determined through sequencing technology against the background of other
      bacteria. The Spearman's rank correlation coefficient determined a good
      correlation between results from culture-dependent microbiology and culture
      independent techniques for all three bacterial groups assessed (correlation
      coefficients for Bifidobacterium sp., Lactobacillus sp. and Enterobacteriaceae
      were 0.380, 0.366 and 0.437, respectively). CONCLUSION: Correlation between the
      two methods implies that a single method is capable of profiling intestinal
      Bifidobacterium, Lactobacillus and Enterobacteriaceae populations. However, both
      methods have advantages that justify their use in tandem. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This is the first extensive study to compare bacterial counts from
      culture-dependent microbiological techniques and from next generation sequencing
      technologies.

PMID- 21718397
TI  - Should chronic catarrh patients seen in primary care be referred for further
      investigations?
AB  - BACKGROUND: Chronic catarrh is commonly encountered in primary care, but often
      presents a quandary to the clinician because the history of postnasal or
      pharyngeal mucus build-up is frequently at odds with the absence of physical
      findings. As with certain other medically mysterious syndromes, the value of
      often costly investigation remains unclear in both the primary and the secondary
      care settings. Indeed, investigation may reassure the physician more than the
      patient (1) and could even prove counter-productive through reinforcement of the
      patient's belief about the presence of significant pathology (2). AIM: To
      establish the benefit of referral of chronic catarrh patients for specialist
      investigation. DESIGN: A cross-sectional survey. SETTING: A total of 138 patients
      referred to secondary care with chronic catarrh, postnasal drip or throat
      clearing in the north of England. METHODS: Subjects completed three disease
      specific symptom-scoring questionnaires (RSI, SNOT-20 and GETS). Investigations
      performed were saccharin clearance time, nasendoscopy, skinprick allergy testing
      and CT of sinuses. Results were compared with published values. RESULTS: Catarrh
      patients scored highly on all three symptom questionnaires. Nasendoscopy was
      normal in 70% of patients, with the remainder demonstrating mostly simple mucus
      (20%), lymphoid tissue (6%) or mucopus (2%). Only 6 of the 136 patients tested
      had a prolonged saccharin clearance time greater than 30 min. The mean score of
      the 63 sinus CT scans obtained was 2.6 (normal range = 0-5). Of patients
      undergoing skinprick testing (n = 45), 30% reacted to one or more inhaled
      allergen. No rhinological investigation yielded results above that expected in
      the general population. CONCLUSION: Chronic catarrh appears to be related more to
      pharyngeal symptom awareness than to pathological postnasal drip or mucus over
      production. Rhinological investigations have a limited role in the management of
      chronic catarrh patients. The principal outcome of ENT referral is likely to be
      reassurance and direction towards patient self-help information.

PMID- 21718398
TI  - A comprehensive review of predictive and prognostic composite factors implicated
      in the heterogeneity of treatment response and outcome across disease areas.
AB  - AIM: To assess and present the current body of evidence regarding composite
      measures associated with differential treatment response or outcome as a result
      of patient heterogeneity and to evaluate their consistency across disease areas.
      METHODS: A comprehensive review of the literature from the last 10 years was
      performed using three databases (PubMed, Embase and Cochrane). All articles that
      met the inclusion/exclusion criteria were selected, abstracted and assessed using
      the NICE level-of-evidence criteria. RESULTS: Forty-nine studies were identified
      in the data abstraction. Approximately one-third focused on existing composite
      measures, and the rest investigated emerging composite factors. The majority of
      studies targeted patients with cancer, cardiovascular disease or psychological
      disorders. As a whole, the composite measures were found to be disease-specific,
      but some composite elements, including age, gender, comorbidities and health
      status, showed consistency across disease areas. To complement these findings,
      common individual factors found in five previous independent disease-specific
      literature assessments were also summarised, including age, gender, treatment
      adherence and satisfaction, healthcare resource utilisation and health status.
      CONCLUSIONS: Composite measures can play an important role in characterising
      heterogeneity of treatment response and outcome in patients suffering from
      various medical conditions. These measures can help clinicians to better
      distinguish between patients with high likelihood to respond well to treatment
      and patients with minimal chances of positive therapeutic outcomes. Herein, the
      individual factors identified can be used to develop novel predictive or
      prognostic composite measures that can be applicable across disease areas.
      Reflecting these cross-disease measures in clinical and public health decisions
      has the distinctive appeal to enable targeted treatment for patients suffering
      from multiple medical conditions, which may ultimately yield significant gains in
      individual outcomes, population health and cost-effective resource allocation.

PMID- 21718399
TI  - Current benign prostatic hyperplasia treatment: impact on sexual function and
      management of related sexual adverse events.
AB  - Benign prostatic hyperplasia (BPH) is a common disease in older men that can lead
      to lower urinary tract symptoms (LUTS). Male sexual dysfunction is also an age
      related condition. Epidemiological studies have confirmed an association between
      BPH/LUTS and sexual dysfunction in ageing men that is independent of the effects
      of age, other co-morbidities and lifestyle factors. Proposed pathophysiological
      mechanisms for BPH/LUTS-associated sexual dysfunction include the nitric
      oxide/cyclic guanosine monophosphate (NO/cGMP) pathway, rho-kinase and endothelin
      1 activity, autonomic nervous system overactivity and the metabolic syndrome, and
      pelvic organ atherosclerosis. Both BPH/LUTS and sexual dysfunction can have a
      substantial negative impact on a man's quality of life. However, urologists and
      primary care physicians appear to under-recognise sexual dysfunction in men with
      BPH/LUTS. Current guidelines recommend alpha-blockers and 5-alpha reductase
      inhibitors, either alone or in combination, among appropriate medical treatment
      options for BPH/LUTS. Randomised, controlled trials demonstrate that these
      therapies can be associated with sexual adverse effects (AEs) such as loss of
      libido, erectile dysfunction and ejaculatory disorders. Sexual dysfunction should
      be fully evaluated in men requiring treatment for BPH/LUTS using validated
      questionnaires. Management of sexual dysfunction in men treated for BPH/LUTS
      should involve assessment of co-morbidities and concomitant medications,
      consideration of lifestyle interventions such as weight loss and increased
      physical activity to improve risk factors and, if necessary, introduction of
      pharmacotherapies. In addition, physicians should provide patients with proper
      counselling on the possible sexual AEs of medical therapies for BPH/LUTS and
      their impact on sexual satisfaction, while being aware of the possibility that
      counselling in itself is likely to influence reported rates of sexual
      dysfunction.

PMID- 21718400
TI  - Novel DNA sequence isolated from blood donors with high transaminase levels.
AB  - AIM:   In Japan, the etiology of 10-20% of cases of acute hepatitis remains
      unclarified. This study was conducted to verify the agent causing non-A-E
      hepatitis. METHODS:   Serum samples from 500 blood donors with elevated alanine
      aminotransferase (ALT) levels were screened by polymerase chain reaction using
      primers constructed from conserved areas of RNA virus helicase. The sequence
      obtained was investigated for viral properties. RESULTS:   Four blood samples
      were found to contain a novel DNA sequence of 9496 bp, which was designated KIs
      V. KIs-V was sensitive to the restriction enzyme SalI and BstXI. Rolling-circle
      amplification produced an excessive amount of KIs-V DNA. In sucrose density
      gradient ultracentrifugation, KIs-V banded at a 1.158-g/cm(3)  density. Detergent
      treatment increased the density of KIs-V. There was no KIs-V DNA amplification
      from human leukocyte DNA. Serial filtration suggested that KIs-V was included in
      a 30-50-nm size particle. In silico analysis revealed that KIs-V contained 13
      potential genes, none of which showed homology to any viral proteins reported.
      One gene showed similarity to a DNA polymerase domain. Strong signals for
      transcription initiation and a CpG island were identified. The nucleotide
      composition of KIs-V showed a characteristic feature of circular DNA genomes that
      contain a replication origin and a terminus. In a preliminary study, KIs-V was
      frequently identified among hepatitis E virus antibody positive individuals with
      elevated ALT levels. CONCLUSION:   A new sequence KIs-V was isolated from blood
      donors with elevated ALT levels. It was suggested that KIs-V is a double-stranded
      circular DNA genome derived from a novel category of enveloped viruses.

PMID- 21718401
TI  - Mdm38 is a 14-3-3-like receptor and associates with the protein synthesis
      machinery at the inner mitochondrial membrane.
AB  - Mitochondrial ribosomes synthesize core subunits of the inner membrane
      respiratory chain complexes. In mitochondria, translation is regulated by mRNA
      specific activator proteins and occurs on membrane-associated ribosomes.
      Mdm38/Letm1 is a conserved membrane receptor for mitochondrial ribosomes and
      specifically involved in respiratory chain biogenesis. In addition, Mdm38 and its
      higher eukaryotic homolog Letm1, function as K(+)/H(+) or Ca(2+)/H(+) antiporters
      in the inner membrane. Here, we identify the conserved ribosome-binding domain
      (RBD) of Mdm38 and determine the crystal structure at 2.1 A resolution.
      Surprisingly, Mdm38(RBD) displays a 14-3-3-like fold despite any similarity to 14
      3-3-proteins at the primary sequence level and thus represents the first 14-3-3
      like protein in mitochondria. The 14-3-3-like domain is critical for respiratory
      chain assembly through regulation of Cox1 and Cytb translation. We show that this
      function can be spatially separated from the ion transport activity of the
      membrane integrated portion of Mdm38. On the basis of the phenotypes observed for
      mdm38Delta as compared to Mdm38 lacking the RBD, we suggest a model that
      combining ion transport and translational regulation into one molecule allows for
      direct coupling of ion flux across the inner membrane, and serves as a signal for
      the translation of mitochondrial membrane proteins via its direct association
      with the protein synthesis machinery.

PMID- 21718402
TI  - Small GTPase Rab12 regulates constitutive degradation of transferrin receptor.
AB  - Transferrin receptor (TfR) is a well-characterized plasma membrane protein that
      travels between the plasma membrane and intracellular membrane compartments.
      Although TfR itself should undergo degradation, the same as other intracellular
      proteins, whether a specific TfR degradation pathway exists has never been
      investigated. In this study, we screened small GTPase Rab proteins, common
      regulators of membrane traffic in all eukaryotes, for proteins that are
      specifically involved in TfR degradation. We performed the screening by three
      sequential methods, i.e. colocalization of Rab with TfR, colocalization with
      lysosomes, and knockdown of Rab by specific small interfering RNA (siRNA), and
      succeeded in identifying Rab12, a previously uncharacterized Rab isoform, as a
      prime candidate among the 60 human or mouse Rabs screened. We showed that
      expression of a constitutive active mutant of Rab12 reduced the amount of TfR
      protein, whereas functional ablation of Rab12 by knockdown of either Rab12 itself
      or its upstream activator Dennd3 increased the amount of TfR protein.
      Interestingly, however, knockdown of Rab12 had no effect on the degradation of
      epidermal growth factor receptor (EGFR) protein, i.e. on a conventional
      degradation pathway. Our findings indicated that TfR is constitutively degraded
      by a Rab12-dependent pathway (presumably from recycling endosomes to lysosomes),
      which is independent of the conventional degradation pathway.

PMID- 21718403
TI  - The generation of curved clathrin coats from flat plaques.
AB  - Flat clathrin lattices or 'plaques' are commonly believed to be the precursors to
      clathrin-coated buds and vesicles. The sequence of steps carrying the flat
      hexagonal lattice into a highly curved polyhedral cage with exactly 12 pentagons
      remains elusive, however, and the large numbers of disrupted interclathrin
      connections in previously proposed conversion pathways make these scenarios
      rather unlikely. The recent notion that clathrin can make controlled small
      conformational transitions opens new avenues. Simulations with a self-assembling
      clathrin model suggest that localized conformational changes in a plaque can
      create sufficiently strong stresses for a dome-like fragment to break apart. The
      released fragment, which is strongly curved but still hexagonal, may subsequently
      grow into a cage by recruiting free triskelia from the cytoplasm, thus building
      all 12 pentagonal faces without recourse to complex topological changes. The
      critical assembly concentration in a slightly acidic in vitro solution is used to
      estimate the binding energy of a cage at 25-40 k(B) T/clathrin.

PMID- 21718404
TI  - Phakic anterior chamber lenses in very high myopia: an 18-month follow up.
AB  - BACKGROUND: To evaluate the efficacy and tolerance of two different foldable
      anterior chamber phakic intraocular lenses for high myopia. DESIGN: A prospective
      interventional case series at the Eye Clinic, Kartal Training and Research
      Hospital, Istanbul, Turkey. PARTICIPANTS: Sixty-two eyes of 31 patients received
      iris-claw lens (group 1) (Artiflex AC 401, Ophtec), and 43 eyes of 22 patients
      received angle-supported lens (group 2) (I-Care, Corneal). METHODS: The mean
      preoperative spherical equivalents for group 1 and group 2 were -12.13 D and 
      18.95 D, respectively. Endothelial cell density was measured at day 1 and at 1,
      3, 6, 12 and 18 months for follow ups. MAIN OUTCOME MEASURES:   Percentage change
      in endothelial cell density and improvement in visual acuity. RESULTS: At the 18
      months follow up, uncorrected visual acuity improved to logMAR 0.37 +/- 0.23 from
      1.60 +/- 0.10 in group 1, and logMAR 0.47 +/- 0.14 from 0.70 +/- 0.20 in group 2;
      best spectacle corrected visual acuity improved to logMAR 0.23 +/- 0.22 from
      logMAR 0.36 +/- 0.14) in group 1, and logMAR 0.29 +/- 0.18 from logMAR 0.50 +/-
      0.20) in group 2 (P<0.001, in both groups). Mean decreased endothelial cell
      density was 241 cells/mm(2) (8.61%) and 223 cells/mm(2) (8.42%) at 18 months
      follow up in group 1 and 2, respectively (P=0.17) but significant in comparison
      to preoperative values for both groups (P<0.001). CONCLUSIONS: Although both iris
      claw and angle-supported lenses offer good refractive outcomes significant
      endothelial cell density was observed at 18 months follow up.

PMID- 21718405
TI  - Evaluation of the difference between intended and measured ablation and its
      impact on refractive outcomes of the wavefront optimize profile and the S001
      Wellington nomogram in myopic spherocylindrical corrections.
AB  - BACKGROUND: To evaluate the level of agreement between intended and measured
      ablation of the wavefront optimize profile corrected by the Wellington nomogram
      in myopic spherocylindrical corrections and assess its impact on refractive
      outcomes. DESIGN: Prospective, university-institute setting. PARTICIPANTS: Eighty
      six participants (86 eyes for photorefractive keratectomy group) and 86
      participants (86 eyes for laser in situ keratomileusis group) recruited in a
      consecutive-if -eligible basis. METHODS: Differences between intended and
      measured ablation were evaluated with Scheimpflug camera. Refractive outcomes
      were evaluated by means of postoperative spherical equivalent, postoperative
      defocus equivalent, contrast sensitivity, correction index, difference vector and
      index of success. MAIN OUTCOME MEASURES: Correlation of visual outcomes with
      intended ablation. RESULTS: Both groups demonstrated significant over-ablations
      (16.7+/-8.5, P<0.001 & 11.8+/-18.5, P<0.001, respectively). Intended ablation was
      the primary determinant of the measured difference (r-square 0.769 & 0.765,
      respectively). Photorefractive keratectomy corrections over 100u had significant
      impact on postoperative spherical equivalent, postoperative defocus equivalent,
      correction index, difference vector and index of success (P=0.044, P=0.05,
      P=0.019, P=0.016, P=0.006, respectively), but laser in situ keratomileusis
      corrections over 100u had significant impact only on postoperative defocus
      equivalent, difference vector and index of success (P=0.04, P=0.05). CONCLUSIONS:
      The results suggest that the wavefront optimize profile seems to over-ablate
      corneal tissue both in photorefractive keratectomy and laser in situ
      keratomileusis. Over-ablation exerts significant impact on refractive outcomes
      only in high spherocylindrical corrections.

PMID- 21718406
TI  - In vivo confocal laser-scanning microscopy to characterize wound repair in rabbit
      corneas after collagen cross-linking.
AB  - BACKGROUND: Collagen cross-linking using the photosensitizer riboflavin combined
      with ultraviolet A light was developed to stiffen the cornea by increasing its
      mechanical and biochemical stability. Investigation of post-treatment events,
      such as wound healing, is important to evaluate possible risks and to optimize
      treatment protocols. This in vivo confocal laser-scanning microscopy study in
      rabbits was conducted to provide a quantitative and qualitative analysis of
      corneal wound repair over 16 weeks following collagen cross-linking. METHODS: Six
      New Zealand White rabbits underwent riboflavin/ultraviolet A cross-linking. In
      vivo confocal laser-scanning microscopy using a Heidelberg Retina Tomograph
      equipped with a Rostock Cornea Module was performed preoperatively and at 2, 4,
      8, 12 and 16 weeks postoperatively. RESULTS: From 2 weeks onwards the epithelium
      demonstrated no abnormalities. Evidence of inflammation was visualized in the
      intermediate, basal cells and Bowman's membrane. Nerve fibre regeneration was
      first noted at 12 weeks. Keratocyte activation and hyperreflective extracellular
      matrix were observed consistently, but by 16 weeks keratocyte activation was
      diminished, and extracellular matrix resumed normal reflectivity. Cell density in
      the posterior stroma and endothelium regained preoperative values by 4 weeks,
      although anterior stroma keratocyte cell density was still reduced by about 10%
      at 16 weeks. CONCLUSIONS: Complete qualitative and quantitative characterization
      of corneal wound repair was achieved by in vivo confocal laser-scanning
      microscopy over 16 weeks following collagen cross-linking in rabbits. In terms of
      assessing the ever-increasing range of cross-linking protocols, in vivo confocal
      laser-scanning microscopy may contribute to minimizing the number of experimental
      animals, because multiple examinations of the same cases are possible over time.

PMID- 21718407
TI  - High prevalence of astigmatism in the 40- to 64-year-old population of Shahroud,
      Iran.
AB  - BACKGROUND:   The prevalence of astigmatism, its axis and determinants were
      determined in the 40- to 64-year-old population of Shahroud, Iran. DESIGN:  
      Population-based cross sectional study. PARTICIPANTS:   Using random cluster
      sampling, 6311 subjects were invited for eye examinations. Of 5190 participants
      (response rate=82.2%), data of 5020 were eligible for analysis. METHODS:
      Participants received visual acuity measurement, manifest refraction and eye
      examinations. MAIN OUTCOME MEASURES: The prevalence of astigmatism based on
      cylinder powers of more than 0.5, 1 and 3 D were studied. RESULTS: The prevalence
      (and 95% confidence interval) of astigmatism based on a cylinder power worse than
      0.5, 1, and 3 D was 49.1% (47.6-50.5), 24.1% (22.9-25.3), and 3.4% (2.9-3.9),
      respectively. In a multiple logistic regression model, the prevalence of
      astigmatism was higher in men (odds ratio=1.25) and increased with age (odds
      ratio for each 5 years=1.21). Higher education was found to be inversely
      correlated to astigmatism (P < 0.001). The prevalence of with-the-rule, against
      the-rule and oblique astigmatism was 12.6%, 25.9% and 10.6%, respectively.
      Oblique astigmatism was significantly higher in women and the older age groups (P
      < 0.001). Against-the-rule astigmatism increased with age from 19.9% in the age
      group of 40-44 to 37.0% in the age group of 60-64 (P < 0.001). CONCLUSIONS:   In
      comparison with those studies conducted in Iran and other countries, the
      prevalence of astigmatism was higher in this study. Astigmatism was higher in men
      and age had an important role in astigmatism and its axis. The prevalence of
      against-the-rule and oblique astigmatism increased with age.

PMID- 21718408
TI  - Diaton tonometry: an assessment of validity and preference against Goldmann
      tonometry.
AB  - BACKGROUND: To assess agreement between the Diaton, a new transpalpebral
      tonometer, and Goldmann applanation tonometry, the accepted gold standard.
      DESIGN: Comparative study of two devices in a hospital setting. PARTICIPANTS: Two
      hundred and fifty-one patients attending the eye casualty and general
      ophthalmology clinics at St James' University Hospital, Leeds between February
      and December 2009. METHODS: Intraocular pressure was measured using Goldmann
      applanation tonometry and Diaton tonometry by one examining ophthalmologist.
      Patient preference for either technique was also recorded. MAIN OUTCOME MEASURES:
      Intraocular pressure measured by Diaton was compared with intraocular pressure
      measured by Goldmann applanation tonometry. Limits of agreement were determined
      using the Bland-Altman method. RESULTS: Two hundred and fifty right eyes
      underwent both Goldmann applanation tonometry and Diaton tonometry. Mean
      intraocular pressure was 13.8 +/- 3.6 mmHg using Goldmann applanation tonometry
      and 13.2 +/- 4.3 mmHg using Diaton tonometry. Upper and lower limits of agreement
      were +8.4 mmHg and -9.6 mmHg, respectively. Order of intraocular pressure
      measurement and positioning did not influence limits of agreement in a clinically
      significant manner. Overall, more patients expressed preference for Diaton
      tonometry (40.2%) than Goldmann applanation tonometry (30.3%). Those aged 50 or
      less were more likely to prefer Diaton tonometry. CONCLUSIONS: The Diaton
      tonometer is portable, lightweight, user-friendly and well tolerated by patients.
      However, it shows poor agreement with Goldmann applanation tonometry, thereby
      precluding it from being regarded as a substitute in routine clinical practice.

PMID- 21718409
TI  - Conjunctival leiomyosarcoma.

PMID- 21718410
TI  - Prevalence of optical coherence tomography-diagnosed postoperative cystoid
      macular oedema in patients following uncomplicated phaco-emulsification cataract
      surgery.
AB  - BACKGROUND: Postoperative cystoid macular oedema is a complication of uneventful
      cataract surgery. Whereas improved surgical techniques have decreased the
      incidence of cystoid macular oedema, it remains a cause of unfavourable visual
      outcome following surgery. Fundus fluorescein angiography has been the 'gold
      standard' for diagnosing subclinical cystoid macular oedema; however, non
      invasive cross-sectional imaging of the retina with optical coherence tomography
      may be equally effective at detecting the condition and offers the ability to
      quantify and repeat results over time. DESIGN: Prospective pre-post case series
      of patients undergoing routine phaco-emulsification surgery. PARTICIPANTS: Eighty
      consecutive patients (100 eyes) with cataracts and an age range of 40 to 90 years
      (mean 76.18). METHODS: Macular thickness of participants was determined using
      time-domain optical coherence tomography preoperatively and after surgery at 1
      day, 1 week, 4 weeks and 6 months. Optical coherence tomography was used to
      diagnose postoperative cystoid macular oedema. MAIN OUTCOME MEASURES: Presence of
      cysts at the macula, identified by optical coherence tomography, in addition to
      foveal and macular thickness (um). RESULTS: Cystoid macular oedema was present in
      5% of eyes. Macular thickness increased after surgery and central foveal
      thickness increased by almost 7% but returned to preoperative levels after 6
      months. Findings also indicate that patients who developed postoperative cystoid
      macular oedema had significantly thicker central foveal thickness of
      approximately 5% compared with those that did not. CONCLUSIONS: Optical coherence
      tomography is a useful, non-invasive diagnostic tool in determining subclinical
      cystoid macular oedema in uncomplicated cataract surgery patients and detects the
      presence of retinal thickening and intra-retinal cysts very soon after surgery,
      thereby facilitating earlier diagnosis and treatment of postoperative cystoid
      macular oedema.

PMID- 21718411
TI  - ReGAE 7: long-term outcomes of augmented trabeculectomy with mitomycin C in
      African Caribbean patients.
AB  - BACKGROUND: To evaluate long-term outcomes and complication rates following
      trabeculectomy with mitomycin C in a case series of African Caribbean patients.
      DESIGN: A prospective, observational and non-comparative case series.
      PARTICIPANTS: Forty-seven consecutive African Caribbean patients (47 eyes) with
      glaucoma. METHODS: All patients underwent augmented trabeculectomy with mitomycin
      C for uncontrolled intraocular pressure (IOP). Survival analysis was performed
      with a minimum of 12 months' follow up. MAIN OUTCOME MEASURES: Surgical success
      was based upon IOP reduction to <= 21 mmHg, <= 18 mmHg and <= 15 mmHg without
      glaucoma medication (complete); or IOP reduction to <= 21 mmHg, <= 18 mmHg and <=
      15 mmHg with or without glaucoma medication (qualified). RESULTS: The mean follow
      up period was 48.6 months. At 3 years post-trabeculectomy 92.6% achieved a
      qualified success and 59.3% a complete success for an IOP <= 21 mmHg. At final
      follow up the mean IOP reduced from 33.7 mmHg to 13.1 mmHg (P < 0.0001). Survival
      rates were 96%, 90% and 86% at 12, 24 and 36 months, respectively, with a mean
      survival time of 97.4 months (95% confidence interval, 86.0-108.8) for an IOP <=
      21 mmHg. Early postoperative hypotony requiring surgical intervention occurred in
      four (8.5%) patients. There were no cases of blebitis, endophthalmitis,
      suprachoroidal haemorrhage, malignant glaucoma or hypotony maculopathy.
      CONCLUSIONS: Good long-term stable IOP can be achieved with low complication
      rates and high success rates amongst African Caribbean patients following
      trabeculectomy with mitomycin C. A proactive postoperative management regime is
      needed to ensure trabeculectomy survival in high-risk populations.

PMID- 21718412
TI  - Bilateral macular infarction secondary to haemodialysis in a patient with chronic
      renal failure.

PMID- 21718413
TI  - Intraocular pressure assessment after laser in situ keratomileusis: a review.
AB  - This paper aims to review the current methods available for the measurement of
      intraocular pressure after myopic laser in situ keratomileusis for the correction
      of myopia. Searches were performed for studies that assessed or compared various
      methods of intraocular pressure assessment. There were 20 eligible studies that
      explored the use of pneumotonometry, pressure phosphene tonometry, rebound
      tonometry, dynamic contour tonometry, statistical modeling, mathematical
      formulae, ocular response analyzer and even measuring intraocular pressure on the
      nasal cornea. Our review shows that an ideal method would be one that is
      independent of corneal factors. Dynamic contour tonometry and pressure phosphene
      tonometry held promise in research settings. More studies need to be done to
      validate the new methods of intraocular pressure assessment, especially in
      glaucoma patients. It is important to empower laser in situ keratomileusis
      patients with knowledge of these difficulties and potential implications for the
      future.

PMID- 21718414
TI  - Protein C deficiency with concurrent essential thrombocytosis and orbital
      compartment syndrome.

PMID- 21718415
TI  - Role of clear lens extraction in adult angle closure disease: a review--comment.

PMID- 21718417
TI  - Early-onset Fuchs endothelial dystrophy with a novel pathological phenotype.

PMID- 21718418
TI  - Bilateral acute severe intraocular pressure elevation requiring filtration
      surgery after implantation of toric Artisan phakic intraocular lenses.

PMID- 21718419
TI  - Fail-to-attend rates in a private ophthalmology clinic by age group.

PMID- 21718420
TI  - To boldly go: individual differences in boldness influence migratory tendency.
AB  - Partial migration, whereby only a fraction of the population migrates, is thought
      to be the most common type of migration in the animal kingdom, and can have
      important ecological and evolutionary consequences. Despite this, the factors
      that influence which individuals migrate and which remain resident are poorly
      understood. Recent work has shown that consistent individual differences in
      personality traits in animals can be ecologically important, but field studies
      integrating personality traits with migratory behaviour are extremely rare. In
      this study, we investigate the influence of individual boldness, an important
      personality trait, upon the migratory propensity of roach, a freshwater fish,
      over two consecutive migration seasons. We assay and individually tag 460 roach
      and show that boldness influences migratory propensity, with bold individuals
      being more likely to migrate than shy fish. Our data suggest that an extremely
      widespread personality trait in animals can have significant ecological
      consequences via influencing individual-level migratory behaviour.

PMID- 21718421
TI  - The Yersinia enterocolitica type 3 secretion system (T3SS) as toolbox for
      studying the cell biological effects of bacterial Rho GTPase modulating T3SS
      effector proteins.
AB  - The bacterial effector proteins IpgB(1) and IpgB(2) of Shigella and Map of
      Escherichia coli activate the Rho GTPases Rac1, RhoA and Cdc42, respectively,
      whereas YopE and YopT of Yersinia inhibit these Rho family GTPases. We
      established a Yersinia toolbox which allows to study the cellular effects of
      these effectors in different combinations in the context of Yersinia type 3
      secretion system (Ysc)-T3SS-mediated injection into HeLa cells. For this purpose
      hybrid proteins were constructed by fusion of YopE with the effector protein of
      interest. As expected, injected hybrid proteins induced membrane ruffles and
      Yersinia uptake for IpgB(1) , stress fibres for IpgB(2) and microspikes for Map.
      By co-infection experiments we could demonstrate (i) IpgB(2) -mediated and ROCK
      dependent inhibition of IpgB(1) -mediated Rac1 effects, (ii) YopT-mediated
      suppression of IpgB(1) -induced Yersinia invasion and (iii) failure of YopE
      mediated suppression of IpgB(1) -induced Yersinia invasion, presumably due to
      preferential inhibition of RhoG by YopE GAP function. By infecting polarized MDCK
      cells we could demonstrate that Map or IpgB(1) but not IpgB(2) affects cell
      monolayer integrity. In summary, the Yersinia toolbox is suitable to study
      cellular effects of effector proteins of diverse bacterial species separately or
      in combination in the context of bacterial T3SS-mediated injection.

PMID- 21718422
TI  - Effect of statin use on biochemical outcome following radical prostatectomy.

PMID- 21718423
TI  - Laparoscopic treatment of benign prostatic hyperplasia (BPH): overview of current
      techniques. Do our patients need it?

PMID- 21718427
TI  - Championing UK Urologists: BAUS serves as their voice around the world. Interview
      by Kevin D. Blanchet.

PMID- 21718428
TI  - LESS: 'Where's the meat'?

PMID- 21718429
TI  - Prevention and management of haematomata after minimally invasive radical
      prostatectomy.

PMID- 21718430
TI  - Gemcitabine chemotherapy for the treatment of metastatic bladder carcinoma.
AB  - OBJECTIVE: * To systematically review the literature on gemcitabine chemotherapy
      for advanced or metastatic bladder cancer. MATERIALS AND METHODS: * The Medical
      Literature Analysis and Retrieval System Onlinedatabase (MEDLINE), the Excerpta
      Medicadatabase (EMBASE), the Cumulative Index to Nursing and Allied Health
      Literature database(CIHNAL), the Cochrane database of randomized trials, the
      Literatura Latino-Americana e do Caribe emCiencias da Saudedatabase (LILACS), and
      Web of Science were searched to identify trials of gemcitabine for metastatic
      bladder cancer. Also searched were international guidelines on metastatic
      prostate cancer, trial registries, and recent systematic reviews. Data on trial
      design, survival, tumour response and toxicity outcomes were extracted from
      relevant studies. RESULTS: * This review identified six randomized trials of
      combined chemotherapy with gemcitabine for the management of unresectable,
      locally advanced or metastatic bladder cancer. * One trial compared gemcitabine
      plus cisplatin (GCis) with methotrexate/vinblastine/doxorubicin/cisplatin(MVAC)
      and found no difference in overall survival (OS; hazard ratio 1.09) but a better
      safety profile with GCis, which was suggested as the treatment of choice. * A
      second trial evaluated GCis against gemcitabine plus carboplatin (GCarbo) and
      reported similar median OS (12.8 vs 9.8 months), disease progression (8.3 vs 7.3
      months) and tumour response rates (66% vs 56%) for the two patient groups. * A
      third trial compared GCis with GCis plus paclitaxel (GCisPac) and showed no
      significant difference in median OS (12.3 vs 15.3 months) and response rates (44%
      vs 43%) but greater toxicity with GCisPac. * A fourth trial assessed GCarbo
      against methotrexate plus carboplatin plus vinblastine in patients unfit for
      cisplatin-based chemotherapy and found similar tumour response rates for each
      regime (38% vs 20%) but the triplet regime was more toxic. * Two other randomized
      studies compared a 2-weekly maintenance regime of gemcitabine plus paclitaxel
      with a 3-weelky regime given for a maximum of six cycles and found that the
      maintenance schedule did not confer any additional survival benefit. * In all, 53
      observational studies of gemcitabine chemotherapy were identified that varied
      considerably in the drug combinations used and schedules. Overall response rates
      (17-78%) and median OS (6.4-24.0 months) were variable with no combination being
      clearly superior. CONCLUSIONS: * Gemcitabine combined chemotherapy is active in
      the management of metastatic bladder cancer. * GCis may be considered an
      alternative regime to MVAC. * GCarbo should be considered for patients unfit for
      cisplatin-based therapy.

PMID- 21718431
TI  - Radical cystectomy for BCG failure: has the timing improved in recent years?

PMID- 21718432
TI  - Prediction of outcomes after radical prostatectomy in patients diagnosed with
      prostate cancer of biopsy Gleason score >= 8 via contemporary multi(>= 12)-core
      prostate biopsy.

PMID- 21718433
TI  - Does tumour size really affect the safety of laparoscopic partial nephrectomy?

PMID- 21718434
TI  - Extraperitoneal ileal conduit.

PMID- 21718435
TI  - From neutrophil extracellular traps release to thrombosis: an overshooting host
      defense mechanism?

PMID- 21718436
TI  - Point mutations regarded as missense mutations cause splicing defects in the
      factor XI gene.
AB  - BACKGROUND: Point mutations within exons are frequently defined as missense
      mutations. In the factor (F)XI gene, three point mutations, c.616C>T in exon 7,
      c.1060G>A in exon 10 and c.1693G>A in exon 14 were reported as missense mutations
      P188S, G336R and E547K, respectively, according to their exonic positions.
      Surprisingly, expression of the three mutations in cells yielded substantially
      higher FXI antigen levels than was expected from the plasma of patients bearing
      these mutations. OBJECTIVES: To test the possibility that the three mutations,
      albeit their positions within exons, cause splicing defects. METHODS AND RESULTS:
      Platelet mRNA analysis of a heterozygous patient revealed that the c.1693A
      mutation caused aberrant splicing. Platelet mRNA of a second compound
      heterozygote for c.616T and c.1060A mutations was undetectable suggesting its
      degradation. Cells transfected with a c.616T minigene favored production of an
      aberrantly spliced mRNA that skips exon 7. Cells transfected with a mutated
      minigene spanning exons 8-10 exhibited a significant decrease in the amount of
      normally spliced mRNA. In silico analysis revealed that the three mutations are
      located within sequences of exonic splicing enhancers (ESEs) that bind special
      proteins and are potentially important for correct splicing. Compensatory
      mutations created near the natural mutations corrected the putative function of
      ESEs thereby restoring normal splicing of exons 7 and 10. CONCLUSIONS: The
      present findings define a new mechanism of mutations in F11 and underscore the
      need to perform expression studies and mRNA analysis of point mutations before
      stating that they are missense mutations.

PMID- 21718437
TI  - The AJT report: news and issues that affect organ and tissue transplantation.
AB  - This month, "The AJT Report" reviews a recent organ allocation error and the use
      of standardized surgical checklists to reduce the incidence of such preventable
      operative errors. Also this month, a look at an increase in registered organ
      donors in the United States.

PMID- 21718439
TI  - After nine years of MELD, fundamental questions of fairness remain.

PMID- 21718440
TI  - Sex-based disparities in liver transplant rates in the United States.
AB  - We sought to characterize sex-based differences in access to deceased donor liver
      transplantation. Scientific Registry of Transplant Recipients data were used to
      analyze n = 78 998 adult candidates listed before (8/1997-2/2002) or after
      (2/2002-2/2007) implementation of Model for End-Stage Liver Disease (MELD)-based
      liver allocation. The primary outcome was deceased donor liver transplantation.
      Cox regression was used to estimate covariate-adjusted differences in transplant
      rates by sex. Females represented 38% of listed patients in the pre-MELD era and
      35% in the MELD era. Females had significantly lower covariate-adjusted
      transplant rates in the pre-MELD era (by 9%; p < 0.0001) and in the MELD era (by
      14%; p < 0.0001). In the MELD era, the disparity in transplant rate for females
      increased as waiting list mortality risk increased, particularly for MELD scores
      >=15. Substantial geographic variation in sex-based differences in transplant
      rates was observed. Some areas of the United States had more than a 30% lower
      covariate-adjusted transplant rate for females compared to males in the MELD era.
      In conclusion, the disparity in liver transplant rates between females and males
      has increased in the MELD era. It is especially troubling that the disparity is
      magnified among patients with high MELD scores and in certain regions of the
      United States.

PMID- 21718441
TI  - Increased incidence and mortality associated with skin cancers after cardiac
      transplant.
AB  - Skin cancer incidence has been shown to be increased in the context of transplant
      associated immunosuppression. There is, however, limited information specifically
      about the incidence of skin cancer after cardiac transplantation in the United
      States. A 10-year retrospective cohort study of 6271 heart transplants at 32 US
      transplant centers revealed increased postprocedure incidence of nonmelanoma and
      melanoma skin cancers, especially cutaneous squamous cell carcinoma, for which
      the incidence increased from 4- to 30-fold compared to the age and gender
      equivalent general population. Incidence of skin cancer in this study was
      consistent with prior single-center data regarding cardiac transplant patients.
      Comparison of all-cause mortality statistics for patients with basal cell
      carcinoma, squamous cell carcinoma and melanoma, respectively, demonstrated
      increased mortality associated with melanoma. Skin cancer screening and
      prophylaxis may be of some utility in reducing morbidity and mortality in cardiac
      transplant patients.

PMID- 21718443
TI  - Hepatitis C virus infection among adolescents and young adults-Massachusetts,
      2002-2009.

PMID- 21718442
TI  - A case-control study of betapapillomavirus infection and cutaneous squamous cell
      carcinoma in organ transplant recipients.
AB  - We examined the association between betapapillomavirus (betaPV) infection and
      cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total
      of 210 organ transplant recipients with previous SCC and 394 controls without
      skin cancer were included. The presence of 25 betaPV types in plucked eyebrow
      hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and
      antibodies for the 15 most prevalent betaPV types were detected using multiplex
      serology. We used multivariate logistic regression models to estimate
      associations between various measures of betaPV infection and SCC. BetaPV DNA was
      highly prevalent (>94%) with multiple types frequently detected in both groups.
      We found a significant association between SCC and the concordant detection of
      both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI
      1.1;2.5). A borderline-significant association with SCC was found for HPV36
      (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and
      HPV24. These data provide further evidence of an association between betaPV
      infection and SCC in organ transplant recipients. Confirmation of a betaPV
      profile predictive of risk for SCC may pave the way for clinically relevant
      pretransplant HPV screening and the development of preventive and therapeutic HPV
      vaccination.

PMID- 21718444
TI  - Edith Helm (April 29, 1935-April 4, 2011): the world's longest surviving
      transplant recipient.

PMID- 21718445
TI  - Immediate and delayed hypersensitivity to corticosteroids.
AB  - Corticosteroids are therapeutic agents used in cases of allergy and intolerance.
      Due to the antiinflammatory effects of the corticosteroids, hypersensitivity
      reactions often are considered to be a paradox. However, delayed-type reaction to
      corticosteroids is a frequent phenomenon in the daily routine. Non-responding
      eczema, development of subacute contact eczema, systemic contact dermatitis or
      maculopapular exanthemas can be a clinical symptom of a delayed-type
      hypersensitivity reaction to corticosteroids. Immediate-type hypersensitivity
      reactions to corticosteroids remain uncommon. Nevertheless, they can take a
      severe clinical course. Patients react with anaphylaxis after systemic
      administration or with aggravation of an allergic reaction under therapy with
      corticosteroids. Allergologic testing is necessary for diagnosis and providing
      alternative corticosteroids in case of an emergency.

PMID- 21718446
TI  - "Standard of reasonable care" in dermatopathology.
AB  - Diagnoses in dermatopathology are capable of improvement. Clinical pictures
      should be evaluated along with skin biopsy specimens whenever possible.

PMID- 21718447
TI  - Surgical option for the correction of Peyronie's disease: an autologous tissue
      engineered endothelialized graft.
AB  - INTRODUCTION: Surgical treatment is indicated in severe cases of Peyronie's
      disease. Incision of the plaque with subsequent graft material implantation is
      the option of choice. Ideal graft tissue is not yet available. AIM: To evaluate
      the use of an autologous tissue-engineered endothelialized graft by the self
      assembly method, for tunica albuginea (TA) reconstruction in Peyronie's disease.
      METHODS: Two TA models were created. Human fibroblasts were isolated from a skin
      biopsy and cultured in vitro until formation of fibroblast sheets. After 4 weeks
      of maturation, human umbilical vein endothelial cells (HUVEC) were seeded on
      fibroblasts sheets and wrapped around a tubular support to form a cylinder of
      about 10 layers. After 21 days of tube maturation, HUVEC were seeded into the
      lumen of the fibroblast tubes for the endothelialized tunica albuginea (ETA). No
      HUVEC were seeded into the lumen for the TA model. Both constructs were placed
      under perfusion in a bioreactor for 1 week. MAIN OUTCOME MEASURES: Histology,
      immunohistochemistry, and burst pressure were performed to characterize mature
      tubular graft. Animal manipulations were also performed to demonstrate the impact
      of endothelial cells in vivo. RESULTS: Histology showed uniform multilayered
      fibroblasts. Extracellular matrix, produced entirely by fibroblasts, presented a
      good staining for collagen 1. Some elastin fibers were also present. For the TA
      model, anti-human von Willebrand antibody revealed the endothelial cells forming
      capillary-like structures. TA model reached a burst pressure of 584 mm Hg and ETA
      model obtained a burst pressure of 719 mm Hg. CONCLUSIONS: This tissue-engineered
      endothelialized tubular graft is structurally similar to normal TA and presents
      an adequate mechanical resistance. The self-assembly method used and the
      autologous property of this model could represent an advantage comparatively to
      other available grafts. Further evaluation including functional testing will be
      necessary to characterize in vivo implantation and behavior of the graft.

PMID- 21718448
TI  - Internal pudendal artery from type 2 diabetic female rats demonstrate elevated
      endothelin-1-mediated constriction.
AB  - INTRODUCTION: Diabetes is a risk factor for female sexual dysfunction (FSD). FSD
      has several etiologies, including a vasculogenic component that could be
      exacerbated in diabetes. The internal pudendal artery supplies blood to the
      vagina and clitoris and diabetes-associated functional abnormalities in this
      vascular bed may contribute to FSD. AIM: The Goto-Kakizaki (GK) rat is a non
      obese model of type 2 diabetes with elevated endothelin-1 (ET-1) activity. We
      hypothesize that female GK rats have diminished sexual responses and that the
      internal pudendal arteries demonstrate increased ET-1 constrictor sensitivity.
      METHODS: Female Wistar and GK rats were used. Apomorphine (APO)-mediated genital
      vasocongestive arousal (GVA) was measured. Functional contraction (ET-1 and
      phenylephrine) and relaxation (acetylcholine, ACh) in the presence or absence of
      the ETA receptor antagonist (ETA R; atrasentan) or Rho-kinase inhibitor (Y-27632)
      were assessed in the internal pudendal and mesenteric arteries. Protein
      expression of ET-1 and RhoA/Rho-kinase signaling pathway was determined in the
      internal pudendal and mesenteric arteries. MAIN OUTCOME MEASURE: APO-mediated
      GVAs; contraction and relaxation of internal pudendal and mesenteric arteries; ET
      1/RhoA/Rho-kinase protein expression. RESULTS: GK rats demonstrated no APO
      induced GVAs. Internal pudendal arteries, but not mesenteric arteries, from GK
      rats exhibited greater contractile sensitivity to ET-1 compared with Wistar
      arteries. ETA R blockade reduced ET-1-mediated constriction in GK internal
      pudendal and mesenteric arteries. Rho-kinase inhibition reduced ET-1-mediated
      constriction of GK internal pudendal but not mesenteric arteries; however, it had
      no effect on arteries from Wistar rats. RhoA protein expression was elevated in
      GK internal pudendal arteries. At the highest concentrations, ACh-mediated
      relaxation was greater in the GK internal pudendal artery; however, no difference
      was observed in the mesenteric artery. CONCLUSIONS: Female GK rats demonstrate
      decreased sexual responses that may be because of increased constrictor
      sensitivity to the ET-1/RhoA/Rho-kinase signaling in the internal pudendal
      artery.

PMID- 21718449
TI  - Neural bases of hypoactive sexual desire disorder in women: an event-related FMRI
      study.
AB  - INTRODUCTION: Although there is an abundant debate regarding the mechanisms
      sustaining one of the most common sexual complaints among women, i.e., female
      hypoactive sexual desire disorder (HSDD), little remains known about the specific
      neural bases of this disorder. AIM: The main goal of this study was to determine
      whether women with HSDD showed differential patterns of activation within the
      brain network that is active for sexual desire in subjects without HSDD. METHODS:
      A total of 28 right-handed women participated in this study (mean age 31.1+/-7.02
      years). Thirteen out of the 28 women had HSDD (HSDD participants), while 15 women
      reported no hypoactive sexual desire disorder (NHSDD participants). Using event
      related functional magnetic resonance imaging (fMRI), we compared the regional
      cerebral blood flow responses between these two groups of participants, while
      they were looking at erotic vs. non-erotic stimuli. MAIN OUTCOME MEASURE: Blood
      oxygenation level dependent (BOLD) signal changes in response to erotic stimuli
      (compared with non-erotic stimuli). Statistical Parametric Mapping was used to
      identify brain regions that demonstrated significant differential activations
      between stimuli and between groups. RESULTS: As expected, behavioral results
      showed that NHSDD participants rated erotic stimuli significantly higher than
      HSDD participants did on a 10-point desirable scale. No rating difference was
      observed for the non-erotic stimuli between NHSDD and HSDD participants. Our
      functional neuroimaging results extended these data by demonstrating two distinct
      types of neural changes in participants with and without HSDD. In comparison with
      HSDD participants, participants without HSDD demonstrated more activation in
      brain areas involved in the processing of erotic stimuli, including intraparietal
      sulcus, dorsal anterior cingulate gyrus, and ento/perirhinal region.
      Interestingly, HSDD participants also showed additional activations in brain
      areas associated with higher order social and cognitive functions, such as
      inferior parietal lobule, inferior frontal gyrus, and posterior medial occipital
      gyrus. CONCLUSION: Together, these findings indicate that HSDD participants do
      not only show a hypo activation in brain areas mediating sexual desire, but also
      a different brain network of hyper activation, which might reflect differences in
      subjective, social, and cognitive interpretations of erotic stimuli.
      Collectively, these data are in line with the incentive motivation model of
      sexual functioning.

PMID- 21718450
TI  - Human papillomavirus genotypes in male genitalia and their concordance among
      pregnant spouses participating in the Finnish Family HPV study.
AB  - INTRODUCTION: Genotype-specific concordance among human papillomavirus (HPV)
      infected spouses is incompletely assessed. HPV concordance is of importance in
      counselling HPV-infected subjects and their partners. AIM: To determine HPV
      genotype distribution and prevalence in semen and urethral samples of young
      fathers and their concordance with HPV-genotypes in cervical and oral mucosal
      samples of their spouses. METHODS: In the Finnish Family HPV study, urethral and
      semen samples were collected from 131 fathers-to-be for HPV genotyping with
      Multimetrix assay. HPV-genotyping data were correlated with the data of the
      cervical and oral mucosal samples of the spouses collected at third trimester
      pregnancy at baseline. MAIN OUTCOME MEASURE: Concordance of HPV-genotypes between
      the spouses. RESULTS: Urethral and/or semen samples tested HPV positive in 47/131
      (35.9%) of the fathers-to-be, more frequently in semen (28/90; 31%) than in
      urethral (29/128; 23%) samples. In women, 18.8% of their cervical and 17.2% of
      the oral samples tested HPV-positive. Of the HPV-positive samples, HPV16 was the
      most frequent genotype, present in 39.3% of semen, 77.3% of mothers' oral, and
      29.2% of cervical samples. Multiple-type infections were found in 24.1% of HPV
      positive urethral and 21.6% of semen samples. In mothers, half of their cervical
      and 4.5% of oral HPV were multiple-type infections. The HPV-genotype-specific
      concordance among spouses ranged from 0% to 9.5%, according to the sampling
      sites. Altogether, eight couples disclosing such a concordance were analyzed
      separately for a risk-profile. Mothers of the HPV-concordant couples reported
      significantly higher number (>6) of life-time sexual partners than did the
      discordant mothers (P=0.030). CONCLUSIONS: Asymptomatic HPV infections were
      common in both parents, while the genotype-specific concordance among spouses was
      low. In both partners, HPV16 is the dominant genotype. HPV6 was a prevalent HPV
      genotype in male genitalia. Female risk profile might enhance the transmission of
      HPV infection to her male partner and increase the genotype-specific HPV
      concordance between the spouses.

PMID- 21718451
TI  - Using genital self-image, body image, and sexual behaviors to predict
      gynecological exam behaviors of college women.
AB  - INTRODUCTION: Despite the benefits of gynecological exams, they continue to be
      underused. A woman's decision to seek gynecological care may be influenced by a
      number of factors including genital image, body image, and sexual behaviors.
      AIMS: The purpose of this study was to assess if genital self-image, body image,
      and sexual behaviors predict gynecological exam behaviors among a convenience
      sample of college women. METHODS: Data were collected from female students
      enrolled in health-related courses at a large southern university. A total of 450
      completed surveys were collected. MAIN OUTCOME MEASURE: Descriptive statistics
      were utilized to analyze participant characteristics. Reliability analyses were
      conducted to assess internal consistency of scales used within the study, using
      Cronbach's alpha coefficient as an indicator of this reliability. Predictive
      discriminant analysis (PDA) was used to indicate the predictor, or group of
      predictors, best suited to predict gynecological exam behaviors of college women.
      RESULTS: Hit rates yielded from the PDA indicate the number of cases correctly
      predicted by the classification functions, with higher hit rates being indicative
      of better predictive capabilities. The following variables were found to be most
      predictive of gynecological exam behaviors: (i) having had a vaginal intercourse
      (VI) partner during the past 3 months (68.2%); (ii) genital self-image paired
      with having had a VI partner (68.2%); (iii) having had a VI partner paired with
      having had an anal intercourse (AI) partner during the past 3 months (68.2%); and
      (iv) genital self-image, VI, and AI combined (68.2%). CONCLUSION: VI behavior was
      found to be the primary predictor of gynecological exam behavior in the current
      study. Understanding the factors influencing a woman's decision to engage in
      regular gynecological exams is important in order for health and medical
      professionals to address the limiting factors in this preventive health measure.

PMID- 21718452
TI  - Unusual surgical repair of the Taussig-Bing heart: evaluation of complex anatomy
      in the adult with congenital heart disease with cardiovascular magnetic
      resonance.
AB  - Double outlet right ventricle is a heterogeneous congenital defect that
      encompasses a variety of anatomic aberrations and physiologic consequences. We
      describe the unusual cardiovascular magnetic resonance anatomic findings and
      sequelae of a 44-year-old man who underwent biventricular repair of double outlet
      right ventricle, subpulmonary type, which included tunneling of the ventricular
      septal defect to the pulmonary artery, right ventricular-to-pulmonary artery
      conduit and Damus-Kaye-Stansel procedure.

PMID- 21718453
TI  - Transcatheter elimination of left-to-right shunts in infants with
      bronchopulmonary dysplasia is feasible and safe.
AB  - OBJECTIVE: To test the hypothesis that transcatheter elimination of left-to-right
      (L-R) cardiac shunts in former premature infants with bronchopulmonary dysplasia
      (BPD) is feasible, safe, and is associated with an improvement in respiratory
      status. DESIGN: Retrospective case review. PATIENTS: Twelve patients with BPD who
      underwent an attempt at transcatheter closure of an L-R shunt lesion within the
      first year of life at a single center. Median weight was 5.4 kg and median age
      was 6 months. Fifteen L-R shunt lesions included patent ductus arteriosus (n =
      1), atrial septal defect (ASD) (n = 9), and aortopulmonary collaterals (n = 5).
      OUTCOME MEASURES: Echocardiographic and clinical markers were collected before
      and after intervention as well as procedural variables including successful
      elimination of the shunt and procedural complications. RESULTS: The L-R shunts
      were successfully occluded in 11/12 (91.6%) patients without any significant
      procedural adverse event. The ASD closure group demonstrated a decrease in right
      heart size after the procedure. All patients required respiratory support prior
      to, and 1 month after, the procedure while only 5/10 (50%) required respiratory
      support at 12 months of age (P = .0129). There was no change in the median weight
      percentile over time. CONCLUSION: Transcatheter occlusion of L-R shunts can be
      performed safely and effectively in children with BPD. Further studies may
      clarify the role of such therapy in improvement in respiratory physiology over
      time.

PMID- 21718454
TI  - Muscular infundibular atresia is associated with coronary ostial atresia in
      pulmonary atresia with intact ventricular septum.
AB  - OBJECTIVE: To determine whether infundibular morphology is associated with
      coronary ostial atresia and/or right ventricle dependent coronary circulation in
      patients with pulmonary atresia with intact ventricular septum. DESIGN: Neonatal
      echocardiograms of patients with pulmonary atresia with intact ventricular septum
      were evaluated for tricuspid valve size and infundibular anatomy (muscular
      pulmonary atresia vs. membranous pulmonary atresia). Right ventricle dependent
      coronary circulation and coronary ostial atresia were diagnosed angiographically.
      Medical record review determined patient outcome. SETTING: Tertiary-care
      pediatric hospital. RESULTS: Of 72 patients, 24 had muscular pulmonary atresia
      including 23 with right ventricle dependent coronary circulation. Fourteen of
      these had unilateral or bilateral coronary ostial atresia. Of 46 patients with
      membranous pulmonary atresia, 5 five had right ventricle dependent coronary
      circulation and none had coronary ostial atresia. Muscular pulmonary atresia
      patients had smaller tricuspid valve z-scores and were less likely to achieve a
      biventricular repair than those with membranous pulmonary atresia (P < .01).
      Muscular pulmonary atresia had 82% sensitivity, 98% specificity, and 96% positive
      predictive value for presence of right ventricle dependent coronary circulation.
      In the group with membranous pulmonary atresia, there were two deaths, no
      transplants, and 23 (48%) achieved a biventricular repair. In contrast, of the 24
      with muscular pulmonary atresia, there were seven deaths, two transplants, and no
      biventricular repairs. CONCLUSIONS: In this cohort, muscular pulmonary atresia
      was strongly associated with right ventricle dependent coronary circulation and
      coronary ostial atresia, and appears to be a useful morphologic marker for poor
      outcome among pulmonary atresia with intact ventricular septum patients. This
      information may be useful during prenatal counseling and for presurgical
      evaluation.

PMID- 21718455
TI  - Streptococcus pneumoniae causing mycotic aneurysm in a pediatric patient with
      coarctation of the aorta.
AB  - Mycotic aneurysms are rare in patients with congenital heart disease, but may
      occur in those with aortic coarctation and abnormal aortic valve. Rapid diagnosis
      of mycotic aneurysm is of extreme importance given the significant reported
      incidence of morbidity and mortality across all age groups. Aortic aneurysm is
      uncommon before the second decade of life, and here we report a 10-year-old male
      patient with new diagnosis of aortic coarctation and bicuspid aortic valve, who
      developed a rapidly enlarging mycotic aneurysm from Streptococcus pneumoniae.
      Cardiac magnetic resonance imaging was crucial in making the diagnosis, as well
      as in follow-up.

PMID- 21718456
TI  - Could submicroscopical chromosomal imbalances cause cono-truncal malformations in
      twins?
AB  - The course of normal heart formation in the embryo has been known for decades,
      but little is known about the genes that control its development. To further
      improve our understanding of the molecular and genetic mechanisms involved in
      congenital heart disease, we screened for submicroscopic chromosomal aberrations
      using bacterial artificial chromosome-based array comparative genomic
      hybridization analysis in two Danish twin pairs, one pair of monozygotic twins
      with tetralogy of Fallot, and one twin pair of unknown zygosity with pulmonary
      valve stenosis. We did not find any major chromosome defects, although a number
      of submicroscopic copy number variations were present. The question of whether
      these submicroscopic chromosomal imbalances alone or in conjunction with unknown
      intrauterine factors causes the observed cono-truncal malformations remains
      unanswered.

PMID- 21718457
TI  - Ramus circumflexissimus--a rare coronary anomaly detected by coronary computed
      tomography angiography.
AB  - We present a case of L-1 type solitary (left) coronary artery that was detected
      with coronary computed tomography angiography and confirmed by invasive coronary
      angiography in a female patient with atypical chest pain. Solitary coronary
      artery anomalies are rare. The L-1 subtype is thought to be a benign type. 

PMID- 21718458
TI  - Implementation of a routine developmental follow-up program for children with
      congenital heart disease: early results.
AB  - OBJECTIVE: To describe the implementation of a routine developmental follow-up
      program for children with congenital heart disease, summarize the developmental
      outcomes of the first clinic visits of the referred patients, and determine what
      factors predict variability in early developmental outcomes. DESIGN: Infants with
      congenital heart disease who had cardiac surgery within the first 30 days of
      life, had a cyanotic lesion (with or without surgery) or were believed to be at
      risk for developmental delay due to comorbid conditions or perioperative
      complications such as seizures or stroke were referred to the program as part of
      standard clinical care. Patients were evaluated using the Bayley Scales of Infant
      and Toddler Development-III. This study reports results from 95 patients (January
      2007-October 2009) who had their first developmental follow-up visit at less than
      1 year of age. RESULTS:   Patients were 7.2 +/- 1.2 months at their first
      evaluation. Bayley scores (mean/standard deviation) for the entire group were:
      Cognitive 100.8 +/- 11.9; Language 96.3 +/- 12.7; and Motor 88.6 +/- 18.6. Scores
      for language and motor achievement were significantly lower than population
      norms. 44% of children had at least one low score (defined as > 1 standard
      deviation below the mean). Of children meeting state criteria for early
      intervention services, 31% were not receiving any early intervention services.
      Risk factors for worse developmental outcomes (P < .05) included more open heart
      procedures, the presence of additional medical/genetic conditions, and the need
      for supplemental tube feedings. Developmental outcomes were not significantly
      related to gestational age, prenatal diagnosis, diagnostic category, or age at
      first surgery. CONCLUSIONS: Implementation of a routine developmental follow-up
      program for congenital heart disease patients is possible and useful in
      identifying those patients who would benefit most from early intervention.

PMID- 21718459
TI  - Discovery and management of diaphragmatic hernia related to abandoned epicardial
      pacemaker wires in a pregnant woman with {S,L,L} transposition of the great
      arteries.
AB  - Epicardial pacemaker leads placed during childhood are often not removed when
      transvenous systems are placed later in life. The risk of complications related
      to retained pacemaker leads and generators is not clear but is generally
      considered low. We report the case of a 23-year-old pregnant woman who presented
      with left upper quadrant pain at 20 weeks gestation. The patient was born with
      {S,L,L} transposition of the great arteries and had high-grade conduction disease
      in infancy compelling epicardial pacemaker placement. A standard transvenous
      pacemaker was placed at age 9 years, without removal of the epicardial system.
      The patient's abdominal pain was attributed to herniation of abdominal contents
      through a diaphragmatic defect at the site of the abandoned epicardial pacing
      wire. Her pain improved spontaneously but worsened later in pregnancy leading to
      repair of the diaphragmatic hernia via anterolateral thoracotomy at 30 weeks
      gestation. The procedure was well tolerated by mother and fetus. At 38 3/7 weeks
      gestation, the patient underwent uneventful delivery by cesarean section for
      breech presentation. This case illustrates the importance of multidisciplinary
      collaboration in the care of women with congenital heart disease.

PMID- 21718460
TI  - Unemployment and widespread influenza in America, 1999-2010.
AB  - BACKGROUND: Research shows that unemployment reduces access to health care and
      vaccines and increases financial difficulty, family conflict, and other sources
      of stress that are known to suppress immune function. In addition, seasonal
      unemployment rates parallel seasonal influenza activity. Following a theory that
      argues that macroeconomic conditions affect population health, this paper
      examines whether there is an association between monthly unemployment rates and
      influenza activity. METHODS: Data from influenza activity surveillance reports
      from the Centers for Disease Control and Prevention are combined with information
      from the Bureau of Labor Statistics on state-level unemployment rates in the U.S.
      for the flu seasons between 1999 and 2010. Pooled time-series cross-section
      logistic regression analyses are conducted to examine the effect of the
      unemployment rate on the likelihood of widespread and/or regional influenza
      activity in the 48 contiguous states throughout this period. A total of 3712
      state-month observations are examined. RESULTS: Net of other factors included in
      the multivariate regression analysis, a one-percentage-point increment in the
      unemployment rate is associated with between a 7.1% and 37.0% increment in the
      odds of widespread influenza (Odds ratio = 1.21). Likewise, a one-percentage
      point increment in the unemployment rate is associated with between a 17.1% and
      44.7% increment in the odds of at least regional influenza (Odds ratio = 1.30).
      Results hold regardless of whether time-varying state-level characteristics are
      included. CONCLUSIONS: Higher state-level unemployment increases the likelihood
      of regional and widespread influenza activity.

PMID- 21718461
TI  - Findings from bipolar offspring studies: methodology matters.
AB  - AIM: High-risk studies provide the opportunity to describe the early natural
      history of bipolar disorder (BD); however, findings have varied substantially. In
      this review, we compare different methods of ascertainment and assessment, and
      their impact on study findings. METHODS: Through a literature search, we
      identified 11 high-risk studies meeting inclusion criteria for this review.
      Studies included were those that focused on lifetime psychopathology in the
      offspring as the main outcome and provided adequate information on the methods of
      family ascertainment, as well as on parent and offspring assessment. We compared
      and contrasted psychopathological outcomes in the offspring among the studies
      using different methods. RESULTS: High-risk studies that identified affected
      parents through their involvement in neurobiological research and confirmed
      diagnosis in the parent and offspring through best estimate procedures tended to
      report lower rates of co-morbidity in the proband parent, lower rates of
      psychopathology in the non-proband parent, lower rates of attention deficit
      hyperactivity disorder and externalizing disorders, and older ages of onset of
      major mood disorders in the offspring compared with studies that identified
      affected parents through self-referral and confirmed diagnosis in the parent and
      offspring through structured research interviews. Studies that identified
      severely ill parents and used semi-structured assessments tended to have an
      intermediate position in terms of outcomes. CONCLUSIONS: This review indicates
      that different methods of family ascertainment and of assessment of parent and
      offspring impact the findings pertaining to lifetime psychopathology and clinical
      course of BD in high-risk studies. The implications of this finding for mapping
      the natural history of BD are discussed.

PMID- 21718462
TI  - Group programmes in early intervention services.
AB  - AIM: Group interventions can be a developmentally appropriate treatment option
      for young people with mental illness; however, there is a paucity of research
      into these programmes. This study had three aims: (i) to document and compare
      both clinicians' and clients' reasons for referral to the Orygen Youth Health
      Recovery Group Program (RGP); (ii) to describe demographic characteristics of
      patients referred to the RGP; and (iii) to delineate and differentiate
      characteristics of clients who do and do not engage with the RGP's activities.
      METHODS: Referral and assessment data from 212 clients referred to the RGP
      between July 2001 and November 2003 were collated and analysed. RESULTS: Main
      reasons for referral to the programme were relationships followed by
      vocational/educational issues. Similarly, the most common goals identified by
      clients were around relationships, followed by time use and vocational issues.
      Clients referred to the RGP but who did not attend were more likely to have a
      psychotic disorder, to be older, unemployed and have difficulties with time
      management and substance use. CONCLUSIONS: Social functioning and vocation are
      important considerations in facilitating young people's recovery from mental
      illness. Such issues can be addressed within the context of psychosocial recovery
      group programmes. Further research is needed not only to address problems
      regarding client engagement but also to evaluate outcomes from participation in
      such programmes.

PMID- 21718463
TI  - Prediction of persistent shoulder pain in general practice: comparing clinical
      consensus from a Delphi procedure with a statistical scoring system.
AB  - BACKGROUND: In prognostic research, prediction rules are generally statistically
      derived. However the composition and performance of these statistical models may
      strongly depend on the characteristics of the derivation sample. The purpose of
      this study was to establish consensus among clinicians and experts on key
      predictors for persistent shoulder pain three months after initial consultation
      in primary care and assess the predictive performance of a model based on
      clinical expertise compared to a statistically derived model. METHODS: A Delphi
      poll involving 3 rounds of data collection was used to reach consensus among
      health care professionals involved in the assessment and management of shoulder
      pain. RESULTS: Predictors selected by the expert panel were: symptom duration,
      pain catastrophizing, symptom history, fear-avoidance beliefs, coexisting neck
      pain, severity of shoulder disability, multisite pain, age, shoulder pain
      intensity and illness perceptions. When tested in a sample of 587 primary care
      patients consulting with shoulder pain the predictive performance of the two
      prognostic models based on clinical expertise were lower compared to that of a
      statistically derived model (Area Under the Curve, AUC, expert-based dichotomous
      predictors 0.656, expert-based continuous predictors 0.679 vs. 0.702 statistical
      model). CONCLUSIONS: The three models were different in terms of composition, but
      all confirmed the prognostic importance of symptom duration, baseline level of
      shoulder disability and multisite pain. External validation in other populations
      of shoulder pain patients should confirm whether statistically derived models
      indeed perform better compared to models based on clinical expertise.

PMID- 21718464
TI  - Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling
      indoor- and outdoor-resting mosquitoes in southern Tanzania.
AB  - BACKGROUND: Resting mosquitoes can easily be collected using an aspirating
      device. The most commonly used mechanical aspirator is the CDC Backpack
      aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has
      been devised and proved to have comparable performance. The following study
      evaluates the Prokopack aspirator compared to the CDC backpack aspirator when
      sampling resting mosquitoes in rural Tanzania. METHODS: Mosquitoes were sampled
      in- and outdoors of 48 typical rural African households using both aspirators.
      The aspirators were rotated between collectors and households in a randomized,
      Latin Square design. Outdoor collections were performed using artificial resting
      places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof
      and from a drop-net. Data were analysed with generalized linear models. RESULTS:
      The number of mosquitoes collected using the CDC Backpack and the Prokopack
      aspirator were not significantly different both in- and outdoors (indoors p =
      0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The
      Prokopack was superior for sampling of drop-nets due to its smaller size. The
      number mosquitoes collected per technician was more consistent when using the
      Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred
      using the it over the CDC backpack aspirator as it weighs considerably less,
      retains its charge for longer and is easier to manoeuvre. CONCLUSIONS: The
      Prokopack proved in the field to be more advantageous than the CDC Backpack
      aspirator. It can be self assembled using simple, low-cost and easily attainable
      materials. This device is a useful tool for researchers or vector-control
      surveillance programs operating in rural Africa, as it is far simpler and quicker
      than traditional means of sampling resting mosquitoes. Further longitudinal
      evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray
      catch for indoor resting catches are recommended.

PMID- 21718465
TI  - Intranodal palisaded myofibroblastoma originating from retroperitoneum: an
      unusual origin.
AB  - BACKGROUND: Intranodal palisaded myofibroblastoma is one of the primary
      mesenchymal tumours. The inguinal region is the commonest site of this rare
      tumour. As there are only about 55 such cases reported in the literature, the
      precise aetiology and pathogenesis have yet to be explained adequately. Here we
      report a case of a 72 year old man presented with incidental finding of
      intranodal palisaded myofibroblastoma in the retroperitoneal region. CASE
      PRESENTATION: A 72-year old man presented with abdominal pain in right upper
      quadrant with an incidental finding of abdominal mass in the right flank. The
      computerised tomogram scan of abdomen confirmed acute cholecystitis with a 5 x 5
      cm retroperitoneal mass. He underwent cholecystectomy with excision of this mass.
      He recovered well following his operation and was discharged from the hospital.
      Histological examination confirmed the diagnosis of intranodal palisaded
      myofibroblastoma. CONCLUSION: To our knowledge, this is the first case of
      intranodal palisaded myofibroblastoma originating from retroperitoneum. Along
      with the rarity of this case, we also discussed its typical histopathological
      findings, aetiology and pathogenesis.

PMID- 21718466
TI  - Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is
      effective.
AB  - BACKGROUND: A screening programme for pregnant women has been in place since the
      1950s in the Netherlands. In 2004 universal HIV screening according to opting out
      was implemented. Here, we describe the evaluation of the effectiveness of
      antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus
      (HBV) and syphilis in preventing mother-to-child transmission, by using various
      data sources. METHODS: The results of antenatal screening (2006-2008) were
      compared with data from pregnant women and newborns from other data sources.
      RESULTS: Each year, around 185,000 pregnant women were screened for HIV, HBV and
      syphilis. Refusal rates for the screening tests were low, and were highest (0.2%)
      for HIV. The estimated annual prevalence of HIV among pregnant women was
      0.05%.Prior to the introduction of screening, 5-10 children were born with HIV
      annually After the introduction of screening in 2004, only 4 children were born
      with HIV (an average of 1 per year). Two of these mothers had become pregnant
      prior to 2004; the third mother was HIV negative at screening and probably became
      infected after screening; the fourth mother's background was unknown. Congenital
      syphilis was diagnosed in fewer than 5 newborns annually and 5 children were
      infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for
      high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in
      newborns had been prevented annually as a result of screening. CONCLUSIONS: The
      screening programme was effective in detecting HIV, HBV and syphilis in pregnant
      women and in preventing transmission to the child. Since the introduction of the
      HIV screening the number of children born with HIV has fallen dramatically.
      PREVIOUS PUBLICATION: [Translation from: 'Prenatale screening op hiv, hepatitis B
      en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine
      ' (NTVG, in Dutch)].

PMID- 21718467
TI  - InterMitoBase: an annotated database and analysis platform of protein-protein
      interactions for human mitochondria.
AB  - BACKGROUND: The mitochondrion is an essential organelle which plays important
      roles in diverse biological processes, such as metabolism, apoptosis, signal
      transduction and cell cycle. Characterizing protein-protein interactions (PPIs)
      that execute mitochondrial functions is fundamental in understanding the
      mechanisms underlying biological functions and diseases associated with
      mitochondria. Investigations examining mitochondria are expanding to the system
      level because of the accumulation of mitochondrial proteomes and human
      interactome. Consequently, the development of a database that provides the entire
      protein interaction map of the human mitochondrion is urgently required. RESULTS:
      InterMitoBase provides a comprehensive interactome of human mitochondria. It
      contains the PPIs in biological pathways mediated by mitochondrial proteins, the
      PPIs between mitochondrial proteins and non-mitochondrial proteins as well as the
      PPIs between mitochondrial proteins. The current version of InterMitoBase covers
      5,883 non-redundant PPIs of 2,813 proteins integrated from a wide range of
      resources including PubMed, KEGG, BioGRID, HPRD, DIP and IntAct. Comprehensive
      curations have been made on the interactions derived from PubMed. All the
      interactions in InterMitoBase are annotated according to the information
      collected from their original sources, GenBank and GO. Additionally,
      InterMitoBase features a user-friendly graphic visualization platform to present
      functional and topological analysis of PPI networks identified. This should aid
      researchers in the study of underlying biological properties. CONCLUSIONS:
      InterMitoBase is designed as an integrated PPI database which provides the most
      up-to-date PPI information for human mitochondria. It also works as a platform by
      integrating several on-line tools for the PPI analysis. As an analysis platform
      and as a PPI database, InterMitoBase will be an important database for the study
      of mitochondria biochemistry, and should be particularly helpful in comprehensive
      analyses of complex biological mechanisms underlying mitochondrial functions.

PMID- 21718468
TI  - Genome-wide expression quantitative trait loci (eQTL) analysis in maize.
AB  - BACKGROUND: Expression QTL analyses have shed light on transcriptional regulation
      in numerous species of plants, animals, and yeasts. These microarray-based
      analyses identify regulators of gene expression as either cis-acting factors that
      regulate proximal genes, or trans-acting factors that function through a variety
      of mechanisms to affect transcript abundance of unlinked genes. RESULTS: A
      hydroponics-based genetical genomics study in roots of a Zea mays IBM2 Syn10
      double haploid population identified tens of thousands of cis-acting and trans
      acting eQTL. Cases of false-positive eQTL, which results from the lack of
      complete genomic sequences from both parental genomes, were described. A
      candidate gene for a trans-acting regulatory factor was identified through
      positional cloning. The unexpected regulatory function of a class I glutamine
      amidotransferase controls the expression of an ABA 8'-hydroxylase pseudogene.
      CONCLUSIONS: Identification of a candidate gene underlying a trans-eQTL
      demonstrated the feasibility of eQTL cloning in maize and could help to
      understand the mechanism of gene expression regulation. Lack of complete genome
      sequences from both parents could cause the identification of false-positive cis-
      and trans-acting eQTL.

PMID- 21718469
TI  - Expanded syringe exchange programs and reduced HIV infection among new injection
      drug users in Tallinn, Estonia.
AB  - BACKGROUND: Estonia has experienced an HIV epidemic among intravenous drug users
      (IDUs) with the highest per capita HIV prevalence in Eastern Europe. We assessed
      the effects of expanded syringe exchange programs (SEP) in the capital city,
      Tallinn, which has an estimated 10,000 IDUs. METHODS: SEP implementation was
      monitored with data from the Estonian National Institute for Health Development.
      Respondent driven sampling (RDS) interview surveys with HIV testing were
      conducted in Tallinn in 2005, 2007 and 2009 (involving 350, 350 and 327 IDUs
      respectively). HIV incidence among new injectors (those injecting for < = 3
      years) was estimated by assuming (1) new injectors were HIV seronegative when
      they began injecting, and (2) HIV infection occurred at the midpoint between
      first injection and time of interview. RESULTS: SEP increased from 230,000
      syringes exchanged in 2005 to 440,000 in 2007 and 770,000 in 2009. In all three
      surveys, IDUs were predominantly male (80%), ethnic Russians (>80%), and young
      adults (mean ages 24 to 27 years). The proportion of new injectors decreased
      significantly over the years (from 21% in 2005 to 12% in 2009, p = 0.005). HIV
      prevalence among all respondents stabilized at slightly over 50% (54% in 2005,
      55% in 2007, 51% in 2009), and decreased among new injectors (34% in 2005, 16% in
      2009, p = 0.046). Estimated HIV incidence among new injectors decreased
      significantly from 18/100 person-years in 2005 and 21/100 person-years in 2007 to
      9/100 person-years in 2009 (p = 0.026). CONCLUSIONS: In Estonia, a transitional
      country, a decrease in the HIV prevalence among new injectors and in the numbers
      of people initiating injection drug use coincided with implementation of large
      scale SEPs. Further reductions in HIV transmission among IDUs are still required.
      Provision of 70 or more syringes per IDU per year may be needed before
      significant reductions in HIV incidence occur.

PMID- 21718470
TI  - Characterisation of five candidate genes within the ETEC F4ab/ac candidate region
      in pigs.
AB  - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) that express the F4ab and
      F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding
      industry, infecting both newborn and weaned piglets. Some pigs are resistant to
      this infection, and susceptibility is inherited as a simple dominant Mendelian
      trait. Indentifying the genetics behind this trait will greatly benefit pig
      welfare as well as the pig breeding industry by providing an opportunity to
      select against genetically susceptible animals, thereby reducing the number of
      diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a
      2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes.
      FINDINGS: The coding regions of five candidate genes for susceptibility to ETEC
      F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5
      Mb region, were investigated for the presence of possible causative mutations. A
      total of 34 polymorphisms were identified in either coding regions or their
      flanking introns. The genotyping data for two of those were found to perfectly
      match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11
      of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional
      profiles of the five genes were investigated in a porcine tissue panel including
      various intestinal tissues. All five genes were expressed in intestinal tissues
      at different levels but none of the genes were found differentially expressed
      between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the
      tested tissues. CONCLUSIONS: None of the identified polymorphisms are obvious
      causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on
      the level of the overall mRNA expression nor predicted to influence the
      composition of the amino acids composition. However, we cannot exclude that the
      five tested genes are bona fide candidate genes for susceptibility to ETEC
      F4ab/ac infection since the identified polymorphism might affect the
      translational apparatus, alternative splice forms may exist and post
      translational mechanisms might contribute to disease susceptibility.

PMID- 21718471
TI  - Cost-effectiveness of intensive inpatient treatments for severely obese children
      and adolescents in the Netherlands; a randomized controlled trial (HELIOS).
AB  - BACKGROUND: Intensive combined lifestyle interventions are the recommended
      treatment for severely obese children and adolescents, but there is a lack of
      studies and their cost-effectiveness. The objective of this study is to compare
      the cost-effectiveness of two intensive one-year inpatient treatments and usual
      care for severely obese children and adolescents. METHODS/DESIGN: Participants
      are 40 children aged 8-13 and 40 adolescents aged 13-18 with severe obesity (SDS
      BMI >= 3.0 or SDS-BMI >= 2.3 with obesity related co-morbidity). They will be
      randomized into two groups that will receive a comprehensive treatment program of
      12 months that focuses on nutrition, physical activity and behavior change of the
      participant and their parents. The two programs are the same in total duration
      (12 months), but differ in inpatient treatment duration. Group A will participate
      in a 6 month intensive inpatient treatment program during weekdays, followed by
      six monthly return visits of 2 days. Group B will participate in a 2 month
      intensive inpatient treatment program during weekdays, followed by biweekly
      return visits of 2 days during the next four months, followed by six monthly
      return visits of 2 days. Several different health care professionals are
      involved, such as pediatricians, dieticians, psychologists, social workers,
      nurses and physiotherapists. Results will also be compared to a control group
      that receives usual care. The primary outcome is SDS-BMI. Secondary outcomes
      include quality of life using the EQ-5D and cardiovascular risk factors. Data
      will be collected at baseline and after 6, 12 and 24 months. An economic
      evaluation will be conducted alongside this study. Healthcare consumption will be
      based on actual resource use, using prospective data collection during 2 years
      through cost diaries. Quality Adjusted Life Years (QALYs) will be calculated
      using the EQ-5D. DISCUSSION: This study will provide useful information on the
      effectiveness and cost-effectiveness of inpatient treatment in severely obese
      children and adolescents. Valuable information on long term effects, after 2
      years, is also included. TRIAL REGISTRATION: Netherlands Trial Register (NTR):
      NTR1678.

PMID- 21718472
TI  - New words in human mutagenesis.
AB  - BACKGROUND: The substitution rates within different nucleotide contexts are
      subject to varying levels of bias. The most well known example of such bias is
      the excess of C to T (C > T) mutations in CpG (CG) dinucleotides. The molecular
      mechanisms underlying this bias are important factors in human genome evolution
      and cancer development. The discovery of other nucleotide contexts that have
      profound effects on substitution rates can improve our understanding of how
      mutations are acquired, and why mutation hotspots exist. RESULTS: We compared
      rates of inherited mutations in 1-4 bp nucleotide contexts using reconstructed
      ancestral states of human single nucleotide polymorphisms (SNPs) from intergenic
      regions. Chimp and orangutan genomic sequences were used as outgroups. We
      uncovered 3.5 and 3.3-fold excesses of T > C mutations in the second position of
      ATTG and ATAG words, respectively, and a 3.4-fold excess of A > C mutations in
      the first position of the ACAA word. CONCLUSIONS: Although all the observed
      biases are less pronounced than the 5.1-fold excess of C > T mutations in CG
      dinucleotides, the three 4 bp mutation contexts mentioned above (and their
      complementary contexts) are well distinguished from all other mutation contexts.
      This provides a challenge to discover the underlying mechanisms responsible for
      the observed excesses of mutations.

PMID- 21718473
TI  - Fractalkine is expressed in the human ovary and increases progesterone
      biosynthesis in human luteinised granulosa cells.
AB  - BACKGROUND: Recent evidence from rodent ovaries has demonstrated expression of
      fractalkine and the existence of fractalkine receptor, and showed that there is a
      significant increase in steroidogenesis in response to fractalkine, yet the role
      of fractalkine and CX3CR1 in the human ovary is still unknown. This study aimed
      to determine the expression levels of fractalkine and CX3CR1 in the human ovary
      and to investigate their roles in sexual hormone biosynthesis by human
      luteinising granulosa cells. This is the first detailed report of fractalkine and
      CX3CR1 expression and function in the human ovary. METHODS: Fractalkine and
      CX3CR1 expression levels were measured by immunohistochemistry using ovarian
      tissue from pathological specimens from five individuals. Granulosa cells were
      obtained from patients during IVF treatment. They were cultured and treated with
      increasing doses of hCG with or without fractalkine. Media were collected to
      detect estradiol and progesterone by chemiluminescence. StAR, 3-betaHSD and
      CYP11A expression were determined in granulosa cells treated with or without
      fractalkine by real-time RT-PCR. RESULTS: Fractalkine and CX3CR1 were expressed
      in the human ovary and in luteinising granulosa cells. However, fractalkine
      expression was stronger in luteinising granulosa cells. Treatment with
      fractalkine augmented hCG stimulation of progesterone production in a dose
      dependent manner with concomitant increases in transcript levels for key
      steroidogenic enzymes (StAR, 3-betaHSD and CYP11A) but had no effect on estradiol
      biosynthesis (P<0.05). CONCLUSIONS: Fractalkine and CX3CR1 were found to express
      in human ovary and luteinising granulosa cells. Fractalkine can increase the
      biosynthesis of progesterone in a dose-dependent manner by enhancing transcript
      levels of key steroidogenic enzymes.

PMID- 21718474
TI  - Randomized controlled trial of pulse methyl prednisolone * placebo in treatment
      of pulmonary involvement associated with severe leptospirosis. [ISRCTN74625030].
AB  - BACKGROUND: The lungs are involved in up to 70% of cases of leptospirosis. In the
      more severe forms-bleeding from the lungs and acute respiratory distress syndrome
      the lethality is high. The treatment proposed for leptospirotic pneumonitis
      includes just care for patients in critical condition. Clinical and experimental
      studies point to the involvement of immunological mechanisms in the
      physiopathology of lung damage caused by leptospirosis. The aim of this study is
      to evaluate pulse treatment with methylprednisolone * placebo for leptospirotic
      pneumonitis. STUDY DESIGN: This is a randomized double-blind clinical trial to
      test the efficacy of pulse treatment with methylprednisolone in patients with
      leptospirotic pneumonitis, compared with a placebo. The patients are recruited
      from three hospitals in the city of Recife, in the Brazilian State of Pernambuco.
      The exclusion criteria include patients aged under 15 years, a history of
      hypersensitivity to the use of corticosteroids, the presence of active infection
      of fungal, tuberculous or bacterial origin apart from the infection by leptospira
      itself, the presence of hemoconcentration or atypical lymphocyte count on
      admission to hospital, the presence of co-morbidities that could be responsible
      for the radiological and gasometric alterations used to diagnose leptospirotic
      pneumonitis, evidence of recent cranial trauma, neurosurgery, peptic ulcer, and
      participation in another clinical trial. The patients are followed until they are
      discharged from hospital or die. The intervention consists of endovenous pulse
      treatment with 1 g methylprednisolone for three consecutive days in the study
      group and a placebo in the control group. The primary end-point is mortality from
      leptospirotic pneumonitis. The secondary end-points are: evolution of lung
      disease; the occurrence of nosocomial respiratory infection; duration of
      mechanical ventilation; duration of intensive care unit (ICU) stay; duration of
      hospital stay; occurrence of other infection-related complications; other
      respiratory complications; and adverse effects of methylprednisolone. The study
      is designed to recruit 266 patients and has a statistical "power" of 80% to
      detect a 50% reduction in mortality. DISCUSSION: Lung involvement in
      leptospirosis is a serious manifestation, with a high and variable mortality
      rate. There is still no specific clearly-established treatment. Well-designed
      studies are needed to pave the way towards development of such a treatment.

PMID- 21718475
TI  - Aurora Kinase A expression is associated with lung cancer histological-subtypes
      and with tumor de-differentiation.
AB  - BACKGROUND: Aurora kinase A (AURKA) is a member of serine/threonine kinase
      family. Several kinases belonging to this family are activated in the G2/M phase
      of the cell cycle being involved in mitotic chromosomal segregation. AURKA
      overexpression is significantly associated with neoplastic transformation in
      several tumors and deregulated Aurora Kinases expression leads to chromosome
      instability, thus contributing to cancer progression. The purpose of the present
      study was to investigate the expression of AURKA in non small cell lung cancer
      (NSCLC) specimens and to correlate its mRNA or protein expression with patients'
      clinico-pathological features. MATERIALS AND METHODS: Quantitative real-time PCR
      and immunohistochemistry analysis on matched cancer and corresponding normal
      tissues from surgically resected non-small cell lung cancers (NSCLC) have been
      performed aiming to explore the expression levels of AURKA gene. RESULTS: AURKA
      expression was significantly up-modulated in tumor samples compared to matched
      lung tissue (p<0.01, mean log2(FC)=1.5). Moreover, AURKA was principally up
      modulated in moderately and poorly differentiated lung cancers (p<0.01), as well
      as in squamous and adenocarcinomas compared to the non-invasive
      bronchioloalveolar histotype (p=0.029). No correlation with survival was
      observed. CONCLUSION: These results indicate that in NSCLC AURKA over-expression
      is restricted to specific subtypes and poorly differentiated tumors.

PMID- 21718476
TI  - Emergency department triage scales and their components: a systematic review of
      the scientific evidence.
AB  - Emergency department (ED) triage is used to identify patients' level of urgency
      and treat them based on their triage level. The global advancement of triage
      scales in the past two decades has generated considerable research on the
      validity and reliability of these scales. This systematic review aims to
      investigate the scientific evidence for published ED triage scales. The following
      questions are addressed: 1. Does assessment of individual vital signs or chief
      complaints affect mortality during the hospital stay or within 30 days after
      arrival at the ED?2. What is the level of agreement between clinicians' triage
      decisions compared to each other or to a gold standard for each scale
      (reliability)? 3. How valid is each triage scale in predicting hospitalization
      and hospital mortality? A systematic search of the international literature
      published from 1966 through March 31, 2009 explored the British Nursing Index,
      Business Source Premier, CINAHL, Cochrane Library, EMBASE, and PubMed. Inclusion
      was limited to controlled studies of adult patients (>= 15 years) visiting EDs
      for somatic reasons. Outcome variables were death in ED or hospital and need for
      hospitalization (validity). Methodological quality and clinical relevance of each
      study were rated as high, medium, or low. The results from the studies that met
      the inclusion criteria and quality standards were synthesized applying the
      internationally developed GRADE system. Each conclusion was then assessed as
      having strong, moderately strong, limited, or insufficient scientific evidence.
      If studies were not available, this was also noted.We found ED triage scales to
      be supported, at best, by limited and often insufficient evidence.The ability of
      the individual vital signs included in the different scales to predict outcome is
      seldom, if at all, studied in the ED setting. The scientific evidence to assess
      interrater agreement (reliability) was limited for one triage scale and
      insufficient or lacking for all other scales. Two of the scales yielded limited
      scientific evidence, and one scale yielded insufficient evidence, on which to
      assess the risk of early death or hospitalization in patients assigned to the two
      lowest triage levels on a 5-level scale (validity).

PMID- 21718477
TI  - Trends in colorectal cancer incidence: a period and birth-cohort analysis in a
      well-defined French population.
AB  - BACKGROUND: France stands among high-risk areas for colorectal cancer. Different
      trends in CRC incidence are reported around the world. The aim of this study was
      to provide temporal trends in CRC incidence over a 30-year period in a French
      well-defined population. METHODS: Between 1976 and 2005, 17,028 new cases were
      registered by the Burgundy digestive cancer registry. The mean variations in age
      standardized incidence rates were estimated using a Poisson regression adjusted
      for age for each gender and location. The cumulative risk by birth cohort of
      developing a cancer over the age range 0-74 years was estimated using an age
      cohort model. RESULTS: Incidence rates for right and left colon cancers increased
      more rapidly in males (respectively +11.7% and +10.3% on average by 5-year
      period) than in females (respectively +5.9% and +6.1%). It remained stable for
      sigmoid cancers in males (-0.1%) and decreased in females (-5.2%). It also
      decreased for rectal cancers both in males (-2.7%) and in females (-2.0%). The
      cumulative risk increased from 3.9% for males born around 1900 to 4.9% for those
      born around 1930 and then slightly decreased (4.5% among those born around 1950).
      It remained at the same level for females born around 1900 (2.7%) as for those
      born around 1930 (2.7%) and then slightly increased (2.9%) for those born around
      1950. For right colon cancers, the cumulative risk increased strikingly in
      successive birth cohorts from 0.53% to 1.2% in males and 0.55% to 0.77% in
      females. The corresponding cumulative risks for the left colon were 0.24% and
      0.42% in males and 0.14% and 0.29% in females. For sigmoid cancer, they decreased
      from 1.59% to 1.08% in males, and 0.88% to 0.80% in females. CONCLUSION: Temporal
      variations in incidence rates of colorectal cancers differed according to
      subsite, suggesting different aetiological factors and implications for diagnosis
      and screening strategies. Total colonoscopy must be the preferred strategy in
      high-risk groups or after a positive faecal occult blood test.

PMID- 21718478
TI  - Mental adjustment to cancer and its relation to anxiety, depression, HRQL and
      survival in patients with laryngeal cancer - a longitudinal study.
AB  - BACKGROUND: Using a longitudinal design, aim of this study was to investigate the
      relation between mental adjustment to cancer and anxiety, depression, health
      related quality of life (HRQL) and survival in patients treated for laryngeal
      cancer. METHODS: 95 patients with Tis-T4 laryngeal cancer were assessed at one
      and 12 months after start of treatment, respectively, using the Mini-Mental
      Adjustment to Cancer Scale (Mini-MAC), the European Organisation for Research and
      Treatment of Cancer (EORTC) Study Group on Quality of Life core questionnaire
      (EORTC QLQ-C30) supplemented with the Head and Neck cancer module (QLQ-H&N35) and
      the Hospital Anxiety and Depression (HAD) Scale. For survival analyses patients
      were followed up for a median time of 4.22 years from inclusion. RESULTS: The
      most commonly used adjustment response at both occasions was Fighting Spirit. The
      use of adjustment responses was relatively stable over time. Correlation analyses
      showed that patients using Helpless-Hopeless and Anxious Preoccupation responses
      reported more anxiety and depression, as well as decreased HRQL. Tumour site and
      stage showed no effect on adjustment response. Survival analysis indicated that
      use of a Helpless-Hopeless response was related to poorer survival (HR 1.17, p
      0.001). CONCLUSION: The relation between adjustment responses Helpless-Hopeless
      and Anxious Preoccupation and anxiety, depression, HRQL and possibly poorer
      survival indicate that assessment of mental adjustment should be considered when
      planning treatment and rehabilitation in laryngeal cancer patients.

PMID- 21718479
TI  - Asystole following positive pressure insufflation of right pleural cavity: a case
      report.
AB  - INTRODUCTION: Adverse hemodynamic effects with severe bradycardia have been
      previously reported during positive pressure insufflation of the right thoracic
      cavity in humans. To the best of our knowledge, this is the first report of
      asystole during thoracoscopic surgery with positive pressure insufflation. CASE
      PRESENTATION: A 63-year-old Caucasian woman developed asystole at the onset of
      positive pressure insufflation of her right hemithorax during a thoracoscopic
      single-lung ventilation procedure. Immediate deflation of pleural cavity,
      intravenous glycopyrrolate and atropine administration returned her heart rhythm
      to normal sinus rhythm. The surgery proceeded in the absence of positive pressure
      insufflation without any further complications. CONCLUSIONS: We discuss the
      proposed mechanisms of hemodynamic instability with positive pressure thoracic
      insufflation, and anesthetic and insufflation techniques that decrease the
      likelihood of adverse hemodynamic events.

PMID- 21718480
TI  - Network-based group variable selection for detecting expression quantitative
      trait loci (eQTL).
AB  - BACKGROUND: Analysis of expression quantitative trait loci (eQTL) aims to
      identify the genetic loci associated with the expression level of genes.
      Penalized regression with a proper penalty is suitable for the high-dimensional
      biological data. Its performance should be enhanced when we incorporate
      biological knowledge of gene expression network and linkage disequilibrium (LD)
      structure between loci in high-noise background. RESULTS: We propose a network
      based group variable selection (NGVS) method for QTL detection. Our method
      simultaneously maps highly correlated expression traits sharing the same
      biological function to marker sets formed by LD. By grouping markers, complex
      joint activity of multiple SNPs can be considered and the dimensionality of eQTL
      problem is reduced dramatically. In order to demonstrate the power and
      flexibility of our method, we used it to analyze two simulations and a mouse
      obesity and diabetes dataset. We considered the gene co-expression network,
      grouped markers into marker sets and treated the additive and dominant effect of
      each locus as a group: as a consequence, we were able to replicate results
      previously obtained on the mouse linkage dataset. Furthermore, we observed
      several possible sex-dependent loci and interactions of multiple SNPs.
      CONCLUSIONS: The proposed NGVS method is appropriate for problems with high
      dimensional data and high-noise background. On eQTL problem it outperforms the
      classical Lasso method, which does not consider biological knowledge.
      Introduction of proper gene expression and loci correlation information makes
      detecting causal markers more accurate. With reasonable model settings, NGVS can
      lead to novel biological findings.

PMID- 21718481
TI  - Canine distemper virus induces apoptosis in cervical tumor derived cell lines.
AB  - Apoptosis can be induced or inhibited by viral proteins, it can form part of the
      host defense against virus infection, or it can be a mechanism for viral spread
      to neighboring cells. Canine distemper virus (CDV) induces apoptotic cells in
      lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also
      produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue
      culture. We tested canine distemper virus, a member of the Paramyxoviridae
      family, for the ability to trigger apoptosis in HeLa cells, derived from cervical
      cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa
      cells, we examined apoptotic markers 24 h post infection (pi), by flow cytometry
      assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA
      expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed
      that DNA fragmentation was induced in HeLa cells infected by CDV, and
      immunocytochemistry revealed a significant increase in the levels of the cleaved
      active form of caspase-3 protein, but did not show any difference in expression
      of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this
      observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells
      than control cells; however, there was no statistically significant change in
      caspase-8 mRNA expression profile. Our data suggest that canine distemper virus
      induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway,
      with no participation of the initiator caspase -8 from the extrinsic pathway. In
      conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to
      apoptosis, can be used as a tool in future research for cervical cancer treatment
      and control.

PMID- 21718482
TI  - Evaluation of direct inoculation of the BD PHOENIX system from positive BACTEC
      blood cultures for both Gram-positive cocci and Gram-negative rods.
AB  - BACKGROUND: Rapid identification (ID) and antibiotic susceptibility testing (AST)
      of the causative micro-organism of bloodstream infections result in earlier
      targeting of antibiotic therapy.In order to obtain results of ID and AST up to 24
      hours earlier, we evaluated the accuracy of direct inoculation of the Phoenix
      system from positive blood cultures (BACTEC) by using Serum Separator Tubes to
      harvest bacteria from positive blood cultures. Results were compared to those of
      standard Phoenix procedure. Discrepancies between the two methods were resolved
      by using the API system, E-test or microbroth dilution. RESULTS: ID with the
      direct method was correct for 95.2% of all tested Enterobacteriaceae (n = 42) and
      71.4% of Pseudomonas aeruginosa strains (n = 7).AST with the direct method showed
      a categorical agreement for Gram-negative rods (GNR) of 99.0%, with 0.7% minor
      errors, 0.3% very major errors and no major errors. All antibiotics showed an
      agreement of >95%.The direct method for AST of Staphylococcus (n = 81) and
      Enterococcus (n = 3) species showed a categorical agreement of 95.4%, with a
      minor error rate of 1.1%, a major error rate of 3.1% and a very major error rate
      of 0.4%. All antibiotics showed an agreement of >90%, except for trimethoprim
      sulfamethoxazole and erythromycin. CONCLUSIONS: Inoculation of Phoenix panels
      directly from positive blood cultures can be used to report reliable results of
      AST of GNR a day earlier, as well as ID-results of Enterobacteriaceae. For
      Staphylococcus and Enterococcus species, results of AST can also be reported a
      day earlier for all antibiotics, except for erythromycin and trimethoprim
      sulfamethoxazole.

PMID- 21718483
TI  - Spatial-temporal analysis of non-Hodgkin lymphoma in the NCI-SEER NHL case
      control study.
AB  - BACKGROUND: Exploring spatial-temporal patterns of disease incidence through
      cluster analysis identifies areas of significantly elevated or decreased risk,
      providing potential clues about disease risk factors. Little is known about the
      etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be
      relevant for environmental exposures, and there are no published spatial-temporal
      cluster studies of NHL. METHODS: We conducted a population-based case-control
      study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology,
      and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during
      1998-2000. Using 20-year residential histories, we used generalized additive
      models adjusted for known risk factors to model spatially the probability that an
      individual had NHL and to identify clusters of elevated or decreased NHL risk. We
      evaluated models at five different time periods to explore the presence of
      clusters in a time frame of etiologic relevance. RESULTS: The best model fit was
      for residential locations 20 years prior to diagnosis in Detroit, Iowa, and Los
      Angeles. We found statistically significant areas of elevated risk of NHL in
      three of the four study areas (Detroit, Iowa, and Los Angeles) at a lag time of
      20 years. The two areas of significantly elevated risk in the Los Angeles study
      area were detected only at a time lag of 20 years. Clusters in Detroit and Iowa
      were detected at several time points. CONCLUSIONS: We found significant spatial
      clusters of NHL after allowing for disease latency and residential mobility. Our
      results show the importance of evaluating residential histories when studying
      spatial patterns of cancer.

PMID- 21718484
TI  - Panax ginseng C.A Meyer root extract for moderate chronic obstructive pulmonary
      disease (COPD): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) impairs quality of life
      and leads to premature mortality. COPD sufferers experience progressive
      deterioration of lung function and decreased ability to undertake day-to-day
      activities. Ginseng has been used for thousands of years in Chinese medicine for
      respiratory symptoms. Several controlled clinical trials using ginseng for COPD
      have shown promising clinical effect, however these studies were generally small
      and with some potential bias, prompting the need for rigorously designed studies.
      AIM: The objective of this study is to evaluate the therapeutic value and safety
      profile of a standardised root extract of Panax ginseng C.A Meyer (ginseng) for
      symptomatic relief, with a focus on quality of life (QoL) improvements in
      individuals with moderate (Stage II) COPD FEV1/FVC < 0.7 and FEV1 50%-80%
      predicted. METHODS: This paper describes the design of a randomised, multi
      centre, double-blind, placebo controlled, two-armed parallel clinical trial. Two
      trial sites in Melbourne Australia will proportionately randomise a total of 168
      participants to receive either ginseng capsule (100 mg) or matching placebo twice
      daily for 24 weeks. The primary outcomes will be based on three validated QoL
      questionnaires, St Georges Respiratory Questionnaire (SGRQ), Short Form Health
      Survey (SF-36) and the COPD Assessment Test (CAT). Secondary outcomes are based
      on lung function testing, relief medication usage and exacerbation frequency and
      severity. Safety endpoints include blood tests and adverse event reporting.
      Intention-to-treat will be applied to all data analyses. DISCUSSION: Findings
      from this study may lead to new therapeutic development for chronic respiratory
      diseases, particularly COPD. This protocol may also guide other investigators to
      develop quality herbal medicine clinical trials in the future. TRIAL
      REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR):
      ACTRN12610000768099.

PMID- 21718485
TI  - De Garengeot's hernia in a 60-year-old woman: a case report.
AB  - INTRODUCTION: De Garengeot first described the presence of the appendix within a
      femoral hernia in 1731. CASE PRESENTATION: We report the case of a 66-year-old
      Caucasian woman who presented with acute appendicitis within an incarcerated
      femoral hernia. This is the first reported case of de Garengeot's hernia in the
      Balkan area. CONCLUSIONS: Appropriate management without incurring any delay for
      radiological imaging can be promising for an uneventful postoperative course. The
      treatment of choice of this disease entity is emergency surgery and consists in
      simultaneous appendectomy through the hernia incision and primary hernia repair.
      In patients with large hernia defects or in older people the use of mesh for
      repairing the hernia defect can be an excellent choice.

PMID- 21718486
TI  - Antagonistic effect of Lactobacillus strains against gas-producing coliforms
      isolated from colicky infants.
AB  - BACKGROUND: Infantile colic is a common disturb within the first 3 months of
      life, nevertheless the pathogenesis is incompletely understood and treatment
      remains an open issue. Intestinal gas production is thought to be one of the
      causes of abdominal discomfort in infants suffering from colic. However, data
      about the role of the amount of gas produced by infants' colonic microbiota and
      the correlation with the onset of colic symptoms are scanty. The benefit of
      supplementation with lactobacilli been recently reported but the mechanisms by
      which they exert their effects have not yet been fully defined. This study was
      performed to evaluate the interaction between Lactobacillus spp. strains and gas
      forming coliforms isolated from stools of colicky infants. RESULTS: Strains of
      coliforms were isolated from stools of 45 colicky and 42 control breastfed
      infants in McConkey Agar and identified using PCR with species-specific primers,
      and the BBLTM EnterotubeTM II system for Enterobacteriaceae. Gas-forming
      capability of coliforms was assessed in liquid cultures containing lactose as
      sole carbon source. The average count of total coliforms in colicky infants was
      significantly higher than controls: 5.98 (2.00-8.76) log10 vs 3.90 (2.50-7.10)
      CFU/g of faeces (p = 0.015). The following strains were identified: Escherichia
      coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes,
      Enterobacter cloacae and Enterococcus faecalis. Then, 27 Lactobacillus strains
      were tested for their antagonistic effect against coliforms both by halo-forming
      method and in liquid co-cultures. Lactobacillus delbrueckii subsp. delbrueckii
      DSM 20074 and L. plantarum MB 456 were able to inhibit all coliforms strains
      (halo-forming method), also in liquid co-cultures, thus demonstrating an
      antagonistic activity. CONCLUSIONS: This study shows that two out of 27 strains
      of Lactobacillus examined possess an antimicrobial effect against six species of
      gas-forming coliforms isolated from colicky infants. Our findings may stimulate
      new researches to identify which Lactobacillus strains can improve colicky
      symptoms by acting on coliforms gut colonization.

PMID- 21718487
TI  - Evaluation of LHP(r) (1% hydrogen peroxide) cream versus petrolatum and untreated
      controls in open wounds in healthy horses: a randomized, blinded control study.
AB  - BACKGROUND: Treatment and protection of wounds in horses can be challenging;
      protecting bandages may be difficult to apply on the proximal extremities and the
      body. Unprotected wounds carry an increased risk of bacterial contamination and
      subsequent infection which can lead to delayed wound healing. Topical treatment
      with antimicrobials is one possibility to prevent bacterial colonization or
      infection, but the frequent use of antimicrobials ultimately leads to development
      of bacterial resistance which is an increasing concern in both human and
      veterinary medicine. METHODS: Standardized wounds were created in 10 Standardbred
      mares. Three wounds were made in each horse. Two wounds were randomly treated
      with LHP(r) or petrolatum and the third wound served as untreated control. All
      wounds were assessed daily until complete epithelization. Protocol data were
      recorded on day 2, 6, 11, 16, 21 and 28. Data included clinical scores for
      inflammation and healing, photoplanimetry for calculating wound areas and swab
      cytology to assess bacterial colonization and inflammation. Bacterial cultures
      were obtained on day 2, 6 and 16. RESULTS: Mean time to complete healing for
      LHP(r) treated wounds was 32 days (95%CI=26.9-37.7). Mean time to complete
      healing for petrolatum and untreated control wounds were 41.6 days (95%CI=36.2
      47.0) and 44.0 days (95%CI=38.6-49.4) respectively. Wound healing occurred
      significantly faster in LHP(r) wounds compared to both petrolatum (p=0.0004) and
      untreated controls (p<0.0001). There was no significant difference in time for
      healing between petrolatum and untreated controls. Total scores for bacteria and
      neutrophils were significantly (p<0.0001) lower for LHP(r) treated wounds
      compared to petrolatum from day 16 and onwards. Staphylococcus aureus and
      Streptococcus zooepidemicus were only found in cultures from petrolatum treated
      wounds and untreated controls. CONCLUSIONS: Treatment with LHP(r) reduced
      bacterial colonization and was associated with earlier complete wound healing.
      LHP(r) cream appears to be safe and effective for topical wound treatment or
      wound protection.

PMID- 21718488
TI  - The relationship among adiponectin, high sensitive C reactive protein and
      triacylglycerol level in healthy young persons.
AB  - BACKGROUND: The elevated postprandial triacylglycerol (TG) concentration is
      associated with elevated coronary artery disease. Oral fatty tolerant test (OFTT)
      is less performed in the health. This study was to evaluate the effect of sex and
      body mass index (BMI) on postprandial TG concentration of the low fat meal in
      healthy young persons. This study included 112 healthy college students (18.8+/
      1.6 y). Their body height and weight were measured for body mass index (BMI).
      According to BMI, 27 subjects were in the under-weight subgroup, 60 in the normal
      weight subgroup and 25 in the over-weight subgroup. After overnight fasting low
      fat OFTT (27 g fat, 600 kcal) was performed and the plasma TG and glucose
      concentrations were measured before and at 2, 4 and 6 hour after a fat meal. The
      area under the curve (AUC) of TG was calculated. RESULTS: The fasting TG levels
      were similar and the fasting TG levels gradually increased as BMI increased in
      both sexes. The postprandial TG levels at 2 and 4 h decreased in female, but did
      not significant change in male. In female, the TG curves of 3 BMI subgroups
      showed saddle type, but in male the TG curve of the over-weight subgroup had a
      peak at 2 h, on the other hand the TG curve of under- weight subgroup had a dip
      at 2 h. CONCLUSIONS: Gender and BMI are important influencing factors for TG
      metabolism after fat meal in the youth. The young male persons with over-BMI have
      abnormal TG metabolism.

PMID- 21718489
TI  - A novel procedure for the quantitative analysis of metabolites, storage products
      and transcripts of laser microdissected seed tissues of Brassica napus.
AB  - BACKGROUND: The biology of the seed is complicated by the extensive non
      homogeneity (spatial gradients) in gene expression, metabolic conversions and
      storage product accumulation. The detailed understanding of the mechanisms
      underlying seed growth and storage therefore requires the development of means to
      obtain tissue-specific analyses. This approach also represents an important
      priority in the context of seed biotechnology. RESULTS: We provide a guideline
      and detailed procedures towards the quantitative analysis of laser micro
      dissected (LM) tissues in oilseed rape (Brassica napus). This includes protocols
      for laser microdissection of the seed, and the subsequent extraction and
      quantitative analysis of lipids, starch and metabolites (sugars, sugar
      phosphates, nucleotides, amino acids, intermediates of glycolysis and citric acid
      cycle). We have also developed a protocol allowing the parallel analysis of the
      transcriptome using Brassica-specific microarrays. Some data are presented
      regarding the compartmentation of metabolites within the oilseed rape embryo.
      CONCLUSION: The described methodology allows for the rapid, combined analysis of
      metabolic intermediates, major storage products and transcripts in a tissue
      specific manner. The protocols are robust for oilseed rape, and should be readily
      adjustable for other crop species. The suite of methods applied to LM tissues
      represents an important step in the context of both the systems biology and the
      biotechnology of oilseeds.

PMID- 21718490
TI  - Comparison of renal effects of ibuprofen versus indomethacin during treatment of
      patent ductus arteriosus in contiguous historical cohorts.
AB  - BACKGROUND: Ibuprofen treatment of patent ductus arteriosus (PDA) has been shown
      to be as effective as indomethacin in small randomized controlled trials, with
      possibly fewer adverse effects. However, adverse renal effects of ibuprofen have
      been noted in some trials and suspected in our practice.The purpose of this study
      was to examine whether ibuprofen and indomethacin treatment of PDA have
      comparable effects on renal function as evidenced by urine output and serum
      creatinine. METHODS: Retrospective chart review of 350 patients. Serum creatinine
      and urine output were recorded prior to start of treatment, during each course
      and after the last course of treatment. Pre-treatment mean creatinine and urine
      output values were compared to treatment and post treatment means using 2-factor
      repeated measures ANOVA. RESULTS: 165 patients were treated with indomethacin
      (2005-2006) and 185 received ibuprofen (2007-2008). There was no difference
      between treatment groups in demographics or baseline renal function. For both
      groups, the number of treatment courses was inversely correlated with birth
      weight and gestational age. Analysis of the first course including all patients,
      revealed significant increase in creatinine and decrease in urine output with
      both drugs, with a more pronounced effect of indomethacin on creatinine. In the
      subgroup of 219 patients who received only one treatment course, there was a
      significant increase in creatinine after indomethacin, but not after ibuprofen.
      In the 131 who received 2 or more courses, the decrease in urine output and
      increase in creatinine were not different between drugs. There were significant
      decreases in urine output observed in the second and third courses of ibuprofen
      treatment (both by 0.9 mL/kg/hr). CONCLUSION: Both drugs have a similar short
      term effect on renal function. Indomethacin had a more prominent initial effect,
      while ibuprofen decreased renal function during the second and third courses
      similarly to indomethacin. The changes in renal function seen with ibuprofen
      treatment should be considered in fluid and electrolyte management, especially if
      treatment beyond one course is required.

PMID- 21718491
TI  - Effect of ischemic preconditioning in skeletal muscle measured by functional
      magnetic resonance imaging and spectroscopy: a randomized crossover trial.
AB  - BACKGROUND: Nuclear magnetic resonance (NMR) imaging and spectroscopy have been
      applied to assess skeletal muscle oxidative metabolism. Therefore, in-vivo NMR
      may enable the characterization of ischemia-reperfusion injury. The goal of this
      study was to evaluate whether NMR could detect the effects of ischemic
      preconditioning (IPC) in healthy subjects. METHODS: Twenty-three participants
      were included in two randomized crossover protocols in which the effects of IPC
      were measured by NMR and muscle force assessments. Leg ischemia was administered
      for 20 minutes with or without a subsequent impaired reperfusion for 5 minutes
      (stenosis model). IPC was administered 4 or 48 hours prior to ischemia. Changes
      in 31phosphate NMR spectroscopy and blood oxygen level-dependent (BOLD) signals
      were recorded. 3-Tesla NMR data were compared to those obtained for isometric
      muscular strength. RESULTS: The phosphocreatine (PCr) signal decreased robustly
      during ischemia and recovered rapidly during reperfusion. In contrast to PCr, the
      recovery of muscular strength was slow. During post-ischemic stenosis, PCr
      increased only slightly. The BOLD signal intensity decreased during ischemia,
      ischemic exercise and post-ischemic stenosis but increased during hyperemic
      reperfusion. IPC 4 hours prior to ischemia significantly increased the maximal
      PCr reperfusion signal and mitigated the peak BOLD signal during reperfusion.
      CONCLUSIONS: Ischemic preconditioning positively influenced muscle metabolism
      during reperfusion; this resulted in an increase in PCr production and higher
      oxygen consumption, thereby mitigating the peak BOLD signal. In addition, an
      impairment of energy replenishment during the low-flow reperfusion was detected
      in this model. Thus, functional NMR is capable of characterizing changes in
      reperfusion and in therapeutic interventions in vivo. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00883467.

PMID- 21718492
TI  - The prognostic value of p53 mutation in pediatric marrow hypoplasia.
AB  - BACKGROUND: The tumor suppressor gene p53 is involved in the control of cell
      proliferation, particularly in stressed cells. p 53 gene mutations are the most
      frequent genetic event found in human cancers. Fanconi Anemia (FA) is the most
      common representative of inherited bone marrow failure syndromes (IBMFS) with a
      leukemic propensity. P 53 DNA alteration has not been studied before in Egyptian
      children with FA. PATIENTS AND METHODS: we investigated p53 mutation in the bone
      marrow and peripheral blood of forty children, FA (n = 10), acquired aplastic
      anemia (AAA) (n = 10), and immune thrombocytopenia (ITP) as a control (n = 20),
      using real-time PCR by TaqMan probe assay. RESULTS: Mutation of p53 gene was
      demonstrated in the BM of 90% (9/10) of children with FA, compared to 10% (1/10)
      in AAA (p < 0.001), while, no p53 DNA mutation was seen in the control group. A
      positive correlation between DNA breakage and presence of p53 mutation was seen
      in FA (p < 0.02, r0.81). CONCLUSION: mutation of p53 gene in hypoplastic marrow
      especially FA may represent an early indicator of significant DNA genetic
      alteration with cancer propensity.

PMID- 21718493
TI  - Severe community-acquired adenovirus pneumonia in an immunocompetent 44-year-old
      woman: a case report and review of the literature.
AB  - INTRODUCTION: This case report describes a rare condition: community-acquired
      adenovirus pneumonia in an immunocompetent adult. The diagnosis was achieved by
      using a multiplex real-time reverse transcriptase polymerase chain reaction (RT
      PCR) assay and highlights the usefulness of these novel molecular diagnostic
      techniques in patients hospitalized with acute respiratory illness. We also
      performed a literature search for previously published cases and present a
      summary of the clinical, laboratory and radiological features of this condition.
      CASE PRESENTATION: A 44-year-old immunocompetent Caucasian woman was admitted to
      our hospital with an acute febrile respiratory illness associated with a rash.
      Her blood tests were non-specifically abnormal, and tests for bacterial pathogens
      were negative. Her condition rapidly deteriorated while she was in our hospital
      and required mechanical ventilation and inotropic support. A multiplex real-time
      RT-PCR assay performed on respiratory specimens to detect respiratory viruses was
      negative for influenza but positive for adenovirus DNA. The patient recovered on
      supportive treatment, and antibiotics were stopped after 5 days. CONCLUSIONS:
      Community-acquired adenovirus pneumonia in immunocompetent adult civilians
      presents as a non-specific acute febrile respiratory illness followed by the
      abrupt onset of respiratory failure, often requiring mechanical ventilation. Its
      laboratory and radiological features are typical of viral infections but also are
      non-specific. Novel multiplex real-time RT-PCR testing for respiratory viruses
      enabled us to rapidly make the diagnosis in this case. The new technology could
      be used more widely in patients with acute respiratory illness and has potential
      utility for rationalization of the use of antibiotics and improving infection
      control measures.

PMID- 21718494
TI  - sunTILL: a TILLING resource for gene function analysis in sunflower.
AB  - BACKGROUND: Cultivated sunflower (Helianthus annus L.) is a globally important
      oilseed crop, subjected to intensive genetic and genomic studies. Although
      classical mutagenesis has successfully been applied to Helianthus genus in the
      past, we have developed the first sunflower TILLING resource. RESULTS: To balance
      the maximum mutation density with an acceptable plant survival rate, a 'kill
      curve' analysis was first conducted with different ethylmethanesulfonate (EMS)
      dosages and different exposure times. According to the germination rate, a
      treatment with 0.7% EMS for 6 h was chosen. An M2 progeny of 3,651 fertile plants
      was obtained. Totally, 4.79% of the whole population showed clear aberrant
      phenotypes. A microsatellite analysis on a representative sample of the original
      seed stock and mutant lines confirmed the uniformity of the genetic background of
      plant material. The TILLING procedure was successfully applied to sunflower
      genome, initially by a CelI-nuclease mismatch cleavage assay coupled with a DNA
      pooling level test. To investigate the efficiency of the mutagenic treatment, a
      pilot screening was carried out on 1,152 M2 lines focusing on four genes, three
      involved in the fatty acid biosynthetic pathway and one for downy mildew
      resistance. A total of 9 mutant lines were identified and confirmed by
      sequencing; thereby, the estimated overall mutation frequency for the pilot assay
      resulted to be 1/475 kb. CONCLUSION: A first TILLING population for a high
      throughput identification of EMS-induced point mutations in sunflower genome has
      been successfully obtained. This represents a powerful tool to a better
      understanding of gene function in sunflower.

PMID- 21718495
TI  - Global challenges of implementing human papillomavirus vaccines.
AB  - Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical
      innovation for the universal benefit of all women. The implementation of the
      vaccines, however, is far from universal or equitable. Socio-economically
      marginalized women in emerging and developing, and many advanced economies alike,
      suffer a disproportionately large burden of cervical cancer. Despite the
      marketing of Human Papillomavirus vaccines as the solution to cervical cancer,
      the market authorization (licensing) of the vaccines has not translated into
      universal equitable access. Vaccine implementation for vulnerable girls and women
      faces multiple barriers that include high vaccine costs, inadequate delivery
      infrastructure, and lack of community engagement to generate awareness about
      cervical cancer and early screening tools. For Human Papillomavirus vaccines to
      work as a public health solution, the quality-assured delivery of cheaper
      vaccines must be integrated with strengthened capacity for community-based health
      education and screening.

PMID- 21718496
TI  - Effectiveness of a short-course in improving knowledge and skills on evidence
      based practice.
AB  - BACKGROUND: To assess the effectiveness (change in knowledge and skills measured
      by the Fresno test) of a short course in Evidence Based Practice (EBP) carried
      out in a group of family medicine residents METHODS: Before-after study.
      Participants' were 152 Family Medicine residents in their second year of the
      training programme. Settings were Primary Care Teaching Units in Catalonia.
      Intervention was comprised of a four half-day training course designed to develop
      the knowledge and skills required to practice evidence-based care. The main
      outcome measure was change in EBP knowledge and skills, measured using the
      Spanish version of the Fresno test (score range, 0-212) RESULTS: The mean
      difference between pre-test and post-test was 47.7, a statistically significant
      result with 95% CI of 42.8-52.5 (p < 0.0001). An important improvement was
      observed in the questions related to calculations such as sensitivity,
      specificity, the absolute risk reduction or the number needed to treat. A more
      modest increase was found in the residents' knowledge and skills in finding the
      best clinical evidence, and appraising the validity and applicability of an
      article. Finally, a weak and non-statistically significant improvement was found
      in formulating a clinical question. CONCLUSIONS: The study provides evidence for
      responsiveness to changes in knowledge and skills in EBP after an educational
      intervention.

PMID- 21718497
TI  - Predictive equations not always overestimate the resting energy expenditure in
      amyotrophic lateral sclerosis patients.

PMID- 21718498
TI  - Microglial phagocytosis induced by fibrillar beta-amyloid is attenuated by
      oligomeric beta-amyloid: implications for Alzheimer's disease.
AB  - BACKGROUND: Reactive microglia are associated with beta-amyloid (Abeta) deposit
      and clearance in Alzhiemer's Disease (AD). Paradoxically, entocranial resident
      microglia fail to trigger an effective phagocytic response to clear Abeta
      deposits although they mainly exist in an "activated" state. Oligomeric Abeta
      (oAbeta), a recent target in the pathogenesis of AD, can induce more potent
      neurotoxicity when compared with fibrillar Abeta (fAbeta). However, the role of
      the different Abeta forms in microglial phagocytosis, induction of inflammation
      and oxidation, and subsequent regulation of phagocytic receptor system, remain
      unclear. RESULTS: We demonstrated that Abeta(1-42) fibrils, not Abeta(1-42)
      oligomers, increased the microglial phagocytosis. Intriguingly, the pretreatment
      of microglia with oAbeta(1-42) not only attenuated fAbeta(1-42)-triggered
      classical phagocytic response to fluorescent microspheres but also significantly
      inhibited phagocytosis of fluorescent labeled fAbeta(1-42). Compared with the
      fAbeta(1-42) treatment, the oAbeta(1-42) treatment resulted in a rapid and
      transient increase in interleukin 1beta (IL-1beta) level and produced higher
      levels of tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO),
      prostaglandin E2 (PGE2) and intracellular superoxide anion (SOA). The further
      results demonstrated that microglial phagocytosis was negatively correlated with
      inflammatory mediators in this process and that the capacity of phagocytosis in
      fAbeta(1-42)-induced microglia was decreased by IL-1beta, lippolysaccharide (LPS)
      and tert-butyl hydroperoxide (t-BHP). The decreased phagocytosis could be
      relieved by pyrrolidone dithiocarbamate (PDTC), a nuclear factor-kappaB (NF
      kappaB) inhibitor, and N-acetyl-L-cysteine (NAC), a free radical scavenger. These
      results suggest that the oAbeta-impaired phagocytosis is mediated through
      inflammation and oxidative stress-mediated mechanism in microglial cells.
      Furthermore, oAbeta(1-42) stimulation reduced the mRNA expression of CD36,
      integrin beta1 (Itgb1), and Ig receptor FcgammaRIII, and significantly increased
      that of formyl peptide receptor 2 (FPR2) and scavenger receptor class B1 (SRB1),
      compared with the basal level. Interestingly, the pre-stimulation with oAbeta(1
      42) or the inflammatory and oxidative milieu (IL-1beta, LPS or t-BHP)
      significantly downregulated the fAbeta(1-42)-induced mRNA over-expression of
      CD36, CD47 and Itgb1 receptors in microglial cells. CONCLUSION: These results
      imply that Abeta oligomers induce a potent inflammatory response and subsequently
      disturb microglial phagocytosis and clearance of Abeta fibrils, thereby
      contributing to an initial neurodegenerative characteristic of AD.
      Antiinflammatory and antioxidative therapies may indeed prove beneficial to delay
      the progression of AD.

PMID- 21718499
TI  - Inflammatory stress exacerbates ectopic lipid deposition in C57BL/6J mice.
AB  - BACKGROUND: Chronic systemic inflammation and abnormal free fatty acid metabolism
      are closely related to ectopic lipid deposition. In this study, we investigate if
      inflammation tissue-specifically disrupts lipogenesis and lipolysis in nonadipose
      tissues and adipose tissue, resulting in ectopic lipid deposition in C57BL/6J
      mice. METHODS: We used casein injection in C57BL/6J mice to induce a chronic
      systemic inflammatory stress in vivo. Serum was analyzed for free fatty acid and
      cytokines. Insulin sensitivities were evaluated by glucose and insulin tolerance
      tests. Liver, muscle, adipose tissues were taken for lipid analysis. Real-time
      polymerase chain reaction and western blotting were used to examine the gene and
      protein expression of molecules involved in adipogenesis and lipolysis in
      tissues. RESULTS: Casein injection elevated serum levels of IL-6 and SAA in mice,
      which are associated with increased lipid accumulation in liver and muscle,
      suggesting that chronic systemic inflammation induces ectopic lipid deposition in
      nonadipose tissues. The inflammatory stress upregulated mRNA and protein
      expression of sterol regulatory element binding protein 1, fatty acid synthase,
      and acetyl CoA carboxylase alpha, while inhibited these molecules expression in
      adipose. Interestingly, in the same experimental setting, inflammation increased
      triglyceride lipase and hormone-sensitive lipase expression in white adipose
      tissue. Inflammation also induced insulin resistance and increased serum free
      fatty acid levels in C57BL/6J mice. CONCLUSIONS: Chronic systemic inflammation
      increased lipogenesis in nonadipose tissues and lipolysis in white adipose
      tissue, resulting in ectopic lipid deposition in nonadipose tissues. This
      disturbed free fatty acid homeostasis and caused insulin resistance in C57BL/6J
      mice.

PMID- 21718500
TI  - The functional cancer map: a systems-level synopsis of genetic deregulation in
      cancer.
AB  - BACKGROUND: Cancer cells are characterized by massive dysegulation of
      physiological cell functions with considerable disruption of transcriptional
      regulation. Genome-wide transcriptome profiling can be utilized for early
      detection and molecular classification of cancers. Accurate discrimination of
      functionally different tumor types may help to guide selection of targeted
      therapy in translational research. Concise grouping of tumor types in cancer maps
      according to their molecular profile may further be helpful for the development
      of new therapeutic modalities or open new avenues for already established
      therapies. METHODS: Complete available human tumor data of the Stanford
      Microarray Database was downloaded and filtered for relevance, adequacy and
      reliability. A total of 649 tumor samples from more than 1400 experiments and 58
      different tissues were analyzed. Next, a method to score deregulation of KEGG
      pathway maps in different tumor entities was established, which was then used to
      convert hundreds of gene expression profiles into corresponding tumor-specific
      pathway activity profiles. Based on the latter, we defined a measure for
      functional similarity between tumor entities, which yielded to phylogeny of
      tumors. RESULTS: We provide a comprehensive, easy-to-interpret functional cancer
      map that characterizes tumor types with respect to their biological and
      functional behavior. Consistently, multiple pathways commonly associated with
      tumor progression were revealed as common features in the majority of the tumors.
      However, several pathways previously not linked to carcinogenesis were identified
      in multiple cancers suggesting an essential role of these pathways in cancer
      biology. Among these pathways were 'ECM-receptor interaction', 'Complement and
      Coagulation cascades', and 'PPAR signaling pathway'. CONCLUSION: The functional
      cancer map provides a systematic view on molecular similarities across different
      cancers by comparing tumors on the level of pathway activity. This work resulted
      in identification of novel superimposed functional pathways potentially linked to
      cancer biology. Therefore, our work may serve as a starting point for
      rationalizing combination of tumor therapeutics as well as for expanding the
      application of well-established targeted tumor therapies.

PMID- 21718501
TI  - Comparison of outcomes in patients with stage III versus limited stage IV non
      small cell lung cancer.
AB  - BACKGROUND: Standard therapy for metastatic non small cell lung cancer (NSCLC)
      includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of
      patients with limited metastases treated with curative-intent stereotactic body
      radiation therapy (SBRT) have shown encouraging survival. We hypothesized that
      patients treated with SBRT for limited metastases have comparable outcomes with
      those treated with curative-intent radiation for Stage III NSCLC. METHODS: We
      retrospectively reviewed the records of NSCLC patients treated with curative
      intent radiotherapy at the University of Rochester from 2000-2008. We identified
      3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV
      (initial stage I-II). All stage IV NSCLC patients treated with SBRT had <= 8
      lesions. RESULTS: Of 146 patients, 88% had KPS >= 80%, 30% had > 5% weight loss,
      and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III,
      initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5
      year OS from date of metastatic diagnosis was significantly (p < 0.00001)
      superior among those with limited metastases (<= 8 lesions) versus stage III
      patients who developed extensive metastases not amenable to SBRT (14% vs. 0%).
      CONCLUSION: Stage IV NSCLC is a heterogeneous patient population, with a selected
      cohort apparently faring better than Stage III patients. Though patients with
      limited metastases are favorably selected by virtue of more indolent disease
      and/or less bulky disease burden, perhaps staging these patients differently is
      appropriate for prognostic and treatment characterization. Aggressive local
      therapy may be indicated in these patients, though prospective clinical studies
      are needed.

PMID- 21718502
TI  - Systematic bias in genomic classification due to contaminating non-neoplastic
      tissue in breast tumor samples.
AB  - BACKGROUND: Genomic tests are available to predict breast cancer recurrence and
      to guide clinical decision making. These predictors provide recurrence risk
      scores along with a measure of uncertainty, usually a confidence interval. The
      confidence interval conveys random error and not systematic bias. Standard tumor
      sampling methods make this problematic, as it is common to have a substantial
      proportion (typically 30-50%) of a tumor sample comprised of histologically
      benign tissue. This "normal" tissue could represent a source of non-random error
      or systematic bias in genomic classification. METHODS: To assess the performance
      characteristics of genomic classification to systematic error from normal
      contamination, we collected 55 tumor samples and paired tumor-adjacent normal
      tissue. Using genomic signatures from the tumor and paired normal, we evaluated
      how increasing normal contamination altered recurrence risk scores for various
      genomic predictors. RESULTS: Simulations of normal tissue contamination caused
      misclassification of tumors in all predictors evaluated, but different breast
      cancer predictors showed different types of vulnerability to normal tissue bias.
      While two predictors had unpredictable direction of bias (either higher or lower
      risk of relapse resulted from normal contamination), one signature showed
      predictable direction of normal tissue effects. Due to this predictable direction
      of effect, this signature (the PAM50) was adjusted for normal tissue
      contamination and these corrections improved sensitivity and negative predictive
      value. For all three assays quality control standards and/or appropriate bias
      adjustment strategies can be used to improve assay reliability. CONCLUSIONS:
      Normal tissue sampled concurrently with tumor is an important source of bias in
      breast genomic predictors. All genomic predictors show some sensitivity to normal
      tissue contamination and ideal strategies for mitigating this bias vary depending
      upon the particular genes and computational methods used in the predictor.

PMID- 21718503
TI  - Epithelioid hemangioma of the penis: case report and review of literature.
AB  - INTRODUCTION: Epithelioid hemangioma is a rare vascular tumor found in the penis.
      It is essential to avoid misdiagnosis with Peyronie's disease and penile cancer,
      as management differs significantly. CASE PRESENTATION: We present a case of
      epithelioid hemangioma of the penis in a 50-year-old Caucasian man. We also
      review the literature to evaluate the incidence of benign vascular anomalies of
      the penis and their management. CONCLUSIONS: Epithelioid hemangioma of the penis
      should be considered in the differential diagnosis of patients presenting with
      painful penile lumps. A thorough histological and immunohistochemical examination
      is required to make the diagnosis. Optimal management is complete local excision
      and periodic physical examination for local recurrence.

PMID- 21718504
TI  - Antibacterial activity of some selected medicinal plants of Pakistan.
AB  - BACKGROUND: Screening of the ethnobotenical plants is a pre-requisite to evaluate
      their therapeutic potential and it can lead to the isolation of new bioactive
      compounds. METHODS: The crude extracts and fractions of six medicinal important
      plants (Arisaema flavum, Debregeasia salicifolia, Carissa opaca, Pistacia
      integerrima, Aesculus indica, and Toona ciliata) were tested against three Gram
      positive and two Gram negative ATCC bacterial species using the agar well
      diffusion method. RESULTS: The crude extract of P. integerrima and A. indica were
      active against all tested bacterial strains (12-23 mm zone of inhibition). Other
      four plant's crude extracts (Arisaema flavum, Debregeasia salicifolia, Carissa
      opaca, and Toona ciliata) were active against different bacterial strains. The
      crude extracts showed varying level of bactericidal activity. The aqueous
      fractions of A. indica and P. integerrima crude extract showed maximum activity
      (19.66 and 16 mm, respectively) against B. subtilis, while the chloroform
      fractions of T. ciliata and D. salicifolia presented good antibacterial
      activities (13-17 mm zone of inhibition) against all the bacterial cultures
      tested. CONCLUSION: The methanol fraction of Pistacia integerrima, chloroform
      fractions of Debregeasia salicifolia &Toona ciliata and aqueous fraction of
      Aesculus indica are suitable candidates for the development of novel
      antibacterial compounds.

PMID- 21718506
TI  - Rural-to-urban migration and its implication for new cooperative medical scheme
      coverage and utilization in China.
AB  - BACKGROUND: China has been experiencing the largest rural to urban migration in
      history. Rural-to-urban migrants are those who leave their hometown for another
      place in order to work or live without changing their hukou status, which is a
      household registration system in China, categorizing people as either rural
      residents or urban residents. Rural-to-urban migrants typically find better job
      opportunities in destination cities, and these pay higher salaries than available
      in their home regions. This has served to improve the enrollment rates in the New
      Cooperative Medical Scheme (NCMS) of rural families, protecting households from
      falling into poverty due to diseases. However, current regulations stipulate that
      people who are registered in China's rural hukou can only participate in their
      local NCMS, which in turn poses barriers when migrants seek medical services in
      the health facilities of their destination cities. To examine this issue in
      greater depth, this study examined the associations between migration, economic
      status of rural households, and NCMS enrollment rate, as well as NCMS utilization
      of rural-to-urban migrants. METHODS: A multistage cluster sampling procedure was
      adopted. Our sample included 9,097 households and 36,720 individuals. Chi-square
      test and T-test were used to examine differences between the two populations of
      migrants and non-migrants based on age, gender, marriage status, and highest
      level of education. Ordinal logistic regression was used to examine the
      association between migration and household economic status. Binary logistic
      regression was used to examine the associations between household economic
      status, migration and enrollment in the NCMS. RESULTS: Migration was positively
      associated with improved household economic status. In households with no
      migrants, only 11.3% of the population was in the richest quintile, whereas the
      percentage was more than doubled in households with family members who migrated
      in 2006. Among those using in-patient medical services, 54.3% of migrants in
      comparison with 17.5% of non-migrants used out-of-county hospitals, many of which
      were not designated hospitals (Designated hospitals refer to hospitals where, if
      people use in patient health care, could receive reimbursement from the NCMS.);
      and 55.2% of migrants in comparison with 24.6% of non-migrants, who had the NCMS
      in 2006, received no reimbursement from the NCMS. The three main reasons of not
      receiving reimbursement were: staying in a hospital not designated by the NCMS,
      lack of knowledge of NCMS policies, and encountering difficulties obtaining
      reimbursement. CONCLUSION: Migrants to urban centers improve the economic status
      of their rural household economic of origin. However, obtaining reimbursement
      under the current NCMS for the cost of hospital services provided by undesignated
      providers in urban centers is limited. Addressing this challenge is an emerging
      policy priority.

PMID- 21718505
TI  - 12-month mortality and loss-to-program in antiretroviral-treated children: The
      IeDEA pediatric West African Database to evaluate AIDS (pWADA), 2000-2008.
AB  - BACKGROUND: The IeDEA West Africa Pediatric Working Group (pWADA) was established
      in January 2007 to study the care and treatment of HIV-infected children in this
      region. We describe here the characteristics at antiretroviral treatment (ART)
      initiation and study the 12-month mortality and loss-to-program of HIV-infected
      children followed in ART programs in West Africa. METHODS: Standardized data from
      HIV-infected children followed-up in ART programs were included. Nine clinical
      centers from six countries contributed to the dataset (Benin, Cote d'Ivoire,
      Gambia, Ghana, Mali and Senegal). Inclusion criteria were the followings: age 0
      15 years and initiated triple antiretroviral drug regimens. Baseline time was the
      date of ART initiation. WHO criteria was used to define severe immunosuppression
      based on CD4 count by age or CD4 percent < 15%. We estimated the 12-month Kaplan
      Meier probabilities of mortality and loss-to-program (death or loss to follow-up
      > 6 months) after ART initiation and factors associated with these two outcomes.
      RESULTS: Between June 2000 and December 2007, 2170 children were included.
      Characteristics at ART initiation were the following: median age of 5 years
      (Interquartile range (IQR: 2-9) and median CD4 percentage of 13% (IQR: 7-19). The
      most frequent drug regimen consisted of two nucleoside reverse transcriptase
      inhibitors and one non-nucleoside reverse transcriptase inhibitors (62%). During
      the first 12 months, 169 (7.8%) children died and 461(21.2%) were lost-to
      program. Overall, in HIV-infected children on ART, the 12-month probability of
      death was 8.3% (95% Confidence Interval (CI): 7.2-9.6%), and of loss-to-program
      was 23.1% (95% CI: 21.3-25.0%). Both mortality and loss-to program were
      associated with advanced clinical stage, CD4 percentage < 15% at ART initiation
      and year (> 2005) of ART initiation. CONCLUSION: Innovative and sustainable
      approaches are needed to better document causes of death and increase retention
      in HIV pediatric clinics in West Africa.

PMID- 21718507
TI  - Solid variant of aneurysmal bone cyst of the thoracic spine: a case report.
AB  - INTRODUCTION: The solid variant of aneurysmal bone cyst is rare, and only 13
      cases involving the spine have been reported to date, including seven in the
      thoracic vertebrae. The diagnosis is difficult to secure radiographically before
      biopsy or surgery. CASE REPORT: An 18-year-old Hispanic man presented to our
      facility with a one-year history of left chest pain without any significant
      neurological deficits. An MRI scan demonstrated a 6 cm diameter enhancing multi
      cystic mass centered at the T6 vertebral body with involvement of the left
      proximal sixth rib and extension into the pleural cavity; the spinal cord was
      severely compressed with evidence of abnormal T2 signal changes. Our patient was
      taken to the operating room for a total spondylectomy of T6 with resection of the
      left sixth rib from a single-stage posterior-only approach. The vertebral column
      was reconstructed in a 360 degrees  manner with an expandable titanium cage and
      pedicle screw fixation. Histologically, the resected specimen showed predominant
      solid fibroblastic proliferation, with minor foci of reactive osteoid formation,
      an area of osteoclastic-like giant cells, and cyst-like areas filled with
      erythrocytes and focal hemorrhage, consistent with a predominantly solid variant
      of aneurysmal bone cyst. At 16 months after surgery, our patient remains
      neurologically intact with resolution of his chest and back pain. CONCLUSIONS:
      Because of its rarity, location, and radical treatment approach, we considered
      this case worthy of reporting. The solid variant of aneurysmal bone cyst is
      difficult to diagnose radiologically before biopsy or surgery, and we hope to
      remind other physicians that it should be included in the differential diagnosis
      of any lytic expansile destructive lesion of the spine.

PMID- 21718508
TI  - Left ventricular dysfunction with reduced functional cardiac reserve in diabetic
      and non-diabetic LDL-receptor deficient apolipoprotein B100-only mice.
AB  - BACKGROUND: Lack of suitable mouse models has hindered the studying of diabetic
      macrovascular complications. We examined the effects of type 2 diabetes on
      coronary artery disease and cardiac function in hypercholesterolemic low-density
      lipoprotein receptor-deficient apolipoprotein B100-only mice (LDLR-/
      ApoB100/100). METHODS AND RESULTS: 18-month-old LDLR-/-ApoB100/100 (n = 12),
      diabetic LDLR-/-ApoB100/100 mice overexpressing insulin-like growth factor-II
      (IGF-II) in pancreatic beta cells (IGF-II/LDLR-/-ApoB100/100, n = 14) and age
      matched C57Bl/6 mice (n = 15) were studied after three months of high-fat Western
      diet. Compared to LDLR-/-ApoB100/100 mice, diabetic IGF-II/LDLR-/-ApoB100/100
      mice demonstrated more calcified atherosclerotic lesions in aorta. However,
      compensatory vascular enlargement was similar in both diabetic and non-diabetic
      mice with equal atherosclerosis (cross-sectional lesion area ~60%) and
      consequently the lumen area was preserved. In coronary arteries, both
      hypercholesterolemic models showed significant stenosis (~80%) despite positive
      remodeling. Echocardiography revealed severe left ventricular systolic
      dysfunction and anteroapical akinesia in both LDLR-/-ApoB100/100 and IGF-II/LDLR
      /-ApoB100/100 mice. Myocardial scarring was not detected, cardiac reserve after
      dobutamine challenge was preserved and ultrasructural changes revealed ischemic
      yet viable myocardium, which together with coronary artery stenosis and slightly
      impaired myocardial perfusion suggest myocardial hibernation resulting from
      chronic hypoperfusion. CONCLUSIONS: LDLR-/-ApoB100/100 mice develop significant
      coronary atherosclerosis, severe left ventricular dysfunction with preserved but
      diminished cardiac reserve and signs of chronic myocardial hibernation. However,
      the cardiac outcome is not worsened by type 2 diabetes, despite more advanced
      aortic atherosclerosis in diabetic animals.

PMID- 21718509
TI  - Cross-species chromosome painting tracks the independent origin of multiple sex
      chromosomes in two cofamiliar Erythrinidae fishes.
AB  - BACKGROUND: The Erythrinidae fish family is characterized by a large variation
      with respect to diploid chromosome numbers and sex-determining systems among its
      species, including two multiple X1X2Y sex systems in Hoplias malabaricus and
      Erythrinus erythrinus. At first, the occurrence of a same sex chromosome system
      within a family suggests that the sex chromosomes are correlated and originated
      from ancestral XY chromosomes that were either homomorphic or at an early stage
      of differentiation. To identify the origin and evolution of these X1X2Y sex
      chromosomes, we performed reciprocal cross-species FISH experiments with two sex
      chromosome-specific probes designed from microdissected X1 and Y chromosomes of
      H. malabaricus and E. erythrinus, respectively. RESULTS: Our results yield
      valuable information regarding the origin and evolution of these sex chromosome
      systems. Our data indicate that these sex chromosomes evolved independently in
      these two closed related Erythrinidae species. Different autosomes were first
      converted into a poorly differentiated XY sex pair in each species, and
      additional chromosomal rearrangements produced both X1X2Y sex systems that are
      currently present. CONCLUSIONS: Our data provide new insights into the origin and
      evolution of sex chromosomes, which increases our knowledge about fish sex
      chromosome evolution.

PMID- 21718510
TI  - Expression, immunolocalization and processing of fertilins ADAM-1 and ADAM-2 in
      the boar (Sus domesticus) spermatozoa during epididymal maturation.
AB  - Fertilin alpha (ADAM-1) and beta (ADAM-2) are integral membrane proteins of the
      ADAM family that form a fertilin complex involved in key steps of the sperm
      oocyte membrane interaction. In the present work, we analyzed the presence of
      ADAM-1 and ADAM-2 mRNAs, the spermatozoa proteins' processing and their sub
      cellular localization in epididymal samples from adult boars. ADAM-1 and ADAM-2
      mRNAs were highly produced in the testis, but also in the vas efferens and the
      epididymis. On immunoblots of sperm extracts, ADAM-1 subunit appeared as a main
      reactive band of ~50-55 kDa corresponding to occurrence of different isoforms
      throughout the epididymal duct, especially in the corpus region where isoforms
      ranged from acidic to basic pI. In contrast, ADAM-2 was detected as several bands
      of ~90 kDa, ~75 kDa, ~50-55 kDa and ~40 kDa. The intensity of high molecular mass
      bands decreased progressively in the distal corpus where lower bands were also
      transiently observed, and only the ~40 kDa was observed in the cauda. The
      presence of bands of different molecular weights likely results from a
      proteolytic processing occurring mainly in the testis for ADAM-1, and also
      throughout the caput epididymis for ADAM-2. Immunolocalization showed that
      fertilin migrates from the acrosomal region to the acrosomal ridge during the
      sperm transit from the distal corpus to the proximal cauda. This migration is
      accompanied by an important change in the extractability of a part of ADAM-1 from
      the sperm membrane. This suggests that the fertilin surface migration may be
      triggered by the biochemical changes induced by the epididymal post-translational
      processing of both ADAM1 and ADAM-2. Different patterns of fertilin
      immunolocalization then define several populations of spermatozoa in the cauda
      epididymis. Characterization of such fertilin complex maturation patterns is an
      important step to develop fertility markers based on epididymal maturation of
      surface membrane proteins in domestic mammals.

PMID- 21718511
TI  - Metabolic myopathy presenting with polyarteritis nodosa: a case report.
AB  - INTRODUCTION: To the best of our knowledge, we describe for the first time a
      patient in whom an unusual metabolic myopathy was identified after failure to
      respond to curative therapy for a systemic vasculitis, polyarteritis nodosa. We
      hope this report will heighten awareness of common metabolic myopathies that may
      present later in life. It also speculates on the potential relationship between
      metabolic myopathy and systemic vasculitis. CASE PRESENTATION: A 78-year-old
      African-American woman with a two-year history of progressive fatigue and
      exercise intolerance presented to our facility with new skin lesions and profound
      muscle weakness. Skin and muscle biopsies demonstrated a medium-sized artery
      vasculitis consistent with polyarteritis nodosa. Biochemical studies of the
      muscle revealed diminished cytochrome C oxidase activity (0.78 MUmol/minute/g
      tissue; normal range 1.03 to 3.83 MUmol/minute/g tissue), elevated acid maltase
      activity (23.39 MUmol/minute/g tissue; normal range 1.74 to 9.98 MUmol/minute/g
      tissue) and elevated neutral maltase activity (35.89 MUmol/minute/g tissue;
      normal range 4.35 to 16.03 MUmol/minute/g tissue). Treatment for polyarteritis
      nodosa with prednisone and cyclophosphamide resulted in minimal symptomatic
      improvement. Additional management with a diet low in complex carbohydrates and
      ubiquinone, creatine, carnitine, folic acid, alpha-lipoic acid and ribose
      resulted in dramatic clinical improvement. CONCLUSIONS: Our patient's initial
      symptoms of fatigue, exercise intolerance and progressive weakness were likely
      related to her complex metabolic myopathy involving both the mitochondrial
      respiratory chain and glycogen storage pathways. Management of our patient
      required treatment of both the polyarteritis nodosa as well as metabolic
      myopathy. Metabolic myopathies are common and should be considered in any patient
      with exercise intolerance. Metabolic myopathies may complicate the management of
      various disease states.

PMID- 21718512
TI  - Web-based interventions for weight loss and weight maintenance among rural
      midlife and older women: protocol for a randomized controlled trial.
AB  - BACKGROUND: Weight loss is challenging and maintenance of weight loss is
      problematic among midlife and older rural women. Finding effective interventions
      using innovative delivery methods that can reach underserved and vulnerable
      populations of overweight and obese rural women is a public health challenge.
      METHODS/DESIGN: This Women Weigh-In for Wellness (The WWW study) randomized
      controlled trial is designed to compare the effectiveness of theory-based
      behavior-change interventions using (1) website only, (2) website with peer-led
      support, or (3) website with professional email-counseling to facilitate initial
      weight loss (baseline to 6 months), guided continuing weight loss and maintenance
      (7-18 months) and self-directed weight maintenance (19-30 months) among rural
      women ages 45-69 with a BMI of 28-45. Recruitment efforts using local media will
      target 306 rural women who live within driving distance of a community college
      site where assessments will be conducted at baseline, 3, 6, 12, 18, 24 and 30
      months by research nurses blinded to group assignments. Primary outcomes include
      changes in body weight, % weight loss, and eating and activity behavioral and
      biomarkers from baseline to each subsequent assessment. Secondary outcomes will
      be percentage of women achieving at least 5% and 10% weight loss without regain
      from baseline to 6, 18, and 30 months and achieving healthy eating and activity
      targets. Data analysis will use generalized estimating equations to analyze
      average change across groups and group differences in proportion of participants
      achieving target weight loss levels. DISCUSSION: The Women Weigh-In for Wellness
      study compares innovative web-based alternatives for providing lifestyle behavior
      change interventions for promoting weight loss and weight maintenance among rural
      women. If effective, such interventions would offer potential for reducing
      overweight and obesity among a vulnerable, hard-to-reach, population of rural
      women. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01307644.

PMID- 21718513
TI  - Bilateral spontaneous non-traumatic rupture of the Achilles tendon: a case
      report.
AB  - INTRODUCTION: We present an interesting case of spontaneous non-traumatic
      bilateral rupture of the Achilles tendons, which is a rare condition. Delayed or
      missed diagnosis of Achilles tendon ruptures by primary treating physicians is
      relatively common. CASE REPORT: A 78-year-old Caucasian woman presented with
      spontaneous non-traumatic bilateral rupture of the Achilles tendons. Her symptoms
      started two days after she took ciprofloxacin 500 mg twice daily for a urinary
      tract infection and prednisolone 30 mg once daily for chronic obstructive airway
      disease. CONCLUSION: This case report aims to increase the awareness of this rare
      condition, which should be borne in mind with regard to patients who are on
      steroid therapy and are concurrently started on fluoroquinolones.

PMID- 21718514
TI  - Genome fluctuations in cyanobacteria reflect evolutionary, developmental and
      adaptive traits.
AB  - BACKGROUND: Cyanobacteria belong to an ancient group of photosynthetic
      prokaryotes with pronounced variations in their cellular differentiation
      strategies, physiological capacities and choice of habitat. Sequencing efforts
      have shown that genomes within this phylum are equally diverse in terms of size
      and protein-coding capacity. To increase our understanding of genomic changes in
      the lineage, the genomes of 58 contemporary cyanobacteria were analysed for
      shared and unique orthologs. RESULTS: A total of 404 protein families, present in
      all cyanobacterial genomes, were identified. Two of these are unique to the
      phylum, corresponding to an AbrB family transcriptional regulator and a gene that
      escapes functional annotation although its genomic neighbourhood is conserved
      among the organisms examined. The evolution of cyanobacterial genome sizes
      involves a mix of gains and losses in the clade encompassing complex
      cyanobacteria, while a single event of reduction is evident in a clade dominated
      by unicellular cyanobacteria. Genome sizes and gene family copy numbers evolve at
      a higher rate in the former clade, and multi-copy genes were predominant in large
      genomes. Orthologs unique to cyanobacteria exhibiting specific characteristics,
      such as filament formation, heterocyst differentiation, diazotrophy and symbiotic
      competence, were also identified. An ancestral character reconstruction suggests
      that the most recent common ancestor of cyanobacteria had a genome size of
      approx. 4.5 Mbp and 1678 to 3291 protein-coding genes, 4%-6% of which are unique
      to cyanobacteria today. CONCLUSIONS: The different rates of genome-size evolution
      and multi-copy gene abundance suggest two routes of genome development in the
      history of cyanobacteria. The expansion strategy is driven by gene-family
      enlargment and generates a broad adaptive potential; while the genome
      streamlining strategy imposes adaptations to highly specific niches, also
      reflected in their different functional capacities. A few genomes display extreme
      proliferation of non-coding nucleotides which is likely to be the result of
      initial expansion of genomes/gene copy number to gain adaptive potential,
      followed by a shift to a life-style in a highly specific niche (e.g. symbiosis).
      This transition results in redundancy of genes and gene families, leading to an
      increase in junk DNA and eventually to gene loss. A few orthologs can be
      correlated with specific phenotypes in cyanobacteria, such as filament formation
      and symbiotic competence; these constitute exciting exploratory targets.

PMID- 21718515
TI  - Predicting mutually exclusive spliced exons based on exon length, splice site and
      reading frame conservation, and exon sequence homology.
AB  - BACKGROUND: Alternative splicing of pre-mature RNA is an important process
      eukaryotes utilize to increase their repertoire of different protein products.
      Several types of different alternative splice forms exist including exon
      skipping, differential splicing of exons at their 3'- or 5'-end, intron
      retention, and mutually exclusive splicing. The latter term is used for clusters
      of internal exons that are spliced in a mutually exclusive manner. RESULTS: We
      have implemented an extension to the WebScipio software to search for mutually
      exclusive exons. Here, the search is based on the precondition that mutually
      exclusive exons encode regions of the same structural part of the protein
      product. This precondition provides restrictions to the search for candidate
      exons concerning their length, splice site conservation and reading frame
      preservation, and overall homology. Mutually exclusive exons that are not
      homologous and not of about the same length will not be found. Using the new
      algorithm, mutually exclusive exons in several example genes, a dynein heavy
      chain, a muscle myosin heavy chain, and Dscam were correctly identified. In
      addition, the algorithm was applied to the whole Drosophila melanogaster X
      chromosome and the results were compared to the Flybase annotation and an ab
      initio prediction. Clusters of mutually exclusive exons might be subsequent to
      each other and might encode dozens of exons. CONCLUSIONS: This is the first
      implementation of an automatic search for mutually exclusive exons in eukaryotes.
      Exons are predicted and reconstructed in the same run providing the complete gene
      structure for the protein query of interest. WebScipio offers high quality gene
      structure figures with the clusters of mutually exclusive exons colour-coded, and
      several analysis tools for further manual inspection. The genome scale analysis
      of all genes of the Drosophila melanogaster X chromosome showed that WebScipio is
      able to find all but two of the 28 annotated mutually exclusive spliced exons and
      predicts 39 new candidate exons. Thus, WebScipio should be able to identify
      mutually exclusive spliced exons in any query sequence from any species with a
      very high probability. WebScipio is freely available to academics at
      http://www.webscipio.org.

PMID- 21718516
TI  - Differences in presentation of symptoms between women and men with intermittent
      claudication.
AB  - BACKGROUND: More women than men have PAD with exception for the stage
      intermittent claudication (IC). The purpose of this study was to evaluate
      differences in disease characteristics between men and women when using current
      diagnostic criteria for making the diagnosis IC, defined as ABI < 0.9 and walking
      problems. STUDY DESIGN: Cohort study METHODS: 5040 elderly (median age 71)
      subjects participated in a point-prevalence study 2004. They had their ABI
      measured and filled out questionnaires covering medical history, current
      medication, PAD symptoms and walking ability. The prevalence of IC was 6.5% for
      women and 7.2% for men (P = 0.09). A subset of subjects with IC (N = 56) was
      followed up four years later with the same procedures. They also performed
      additional tests aiming to determine all factors influencing walking ability.
      RESULTS: Men with IC had more concomitant cardiovascular disease and a more
      profound smoking history than women. Women, on the other hand, reported a lower
      walking speed (P < 0.01) and more joint problems (P = 0.018). In the follow up
      cohort ABI, walking ability and amount of atherosclerosis were similar among the
      sexes, but women more often reported atypical IC symptoms. CONCLUSION: Sex
      differences in the description of IC symptoms may influence diagnosis even if
      objective features of PAD are similar. This may influence accuracy of prevalence
      estimates and selection to treatment.

PMID- 21718517
TI  - Phosphoproteins regulated by heat stress in rice leaves.
AB  - BACKGROUND: High temperature is a critical abiotic stress that reduces crop yield
      and quality. Rice (Oryza sativa L.) plants remodel their proteomes in response to
      high temperature stress. Moreover, phosphorylation is the most common form of
      protein post-translational modification (PTM). However, the differential
      expression of phosphoproteins induced by heat in rice remains unexplored.
      METHODS: Phosphoprotein in the leaves of rice under heat stress were displayed
      using two-dimensional electrophoresis (2-DE) and Pro-Q Diamond dye.
      Differentially expressed phosphoproteins were identified by MALDI-TOF-TOF-MS/MS
      and confirmed by Western blotting. RESULTS: Ten heat-phosphoproteins were
      identified from twelve protein spots, including ribulose bisphos-phate
      carboxylase large chain, 2-Cys peroxiredoxin BAS1, putative mRNA binding protein,
      Os01g0791600 protein, OSJNBa0076N16.12 protein, putative H(+)-transporting ATP
      synthase, ATP synthase subunit beta and three putative uncharacterized proteins.
      The identification of ATP synthase subunit beta was further validated by Western
      blotting. Four phosphorylation site predictors were also used to predict the
      phosphorylation sites and the specific kinases for these 10 phosphoproteins.
      CONCLUSION: Heat stress induced the dephosphorylation of RuBisCo and the
      phosphorylation of ATP-beta, which decreased the activities of RuBisCo and ATP
      synthase. The observed dephosphorylation of the mRNA binding protein and 2-Cys
      peroxiredoxin may be involved in the transduction of heat-stress signaling, but
      the functional importance of other phosphoproteins, such as H+-ATPase, remains
      unknown.

PMID- 21718518
TI  - Agent-based simulation for weekend-extension strategies to mitigate influenza
      outbreaks.
AB  - BACKGROUND: Non-pharmaceutical strategies are vital in curtailing impacts of
      influenza and have been intensively studied in public health. However, few
      strategies have explicitly utilized the weekend effect, which has been widely
      reported to be capable of reducing influenza infections. This study aims to
      explore six weekend-extension strategies against seasonal and pandemic flu
      outbreaks. METHODS: The weekend-extension strategies were designed to extend
      regular two-day weekend by one, two and three days, respectively, and in
      combination with either a continuous or discontinuous pattern. Their
      effectiveness was evaluated using an established agent-based spatially explicit
      simulation model in the urbanized area of Buffalo, NY, US. RESULTS: If the
      extensions last more than two days, the weekend-extension strategies can
      remarkably reduce the overall disease attack rate of seasonal flu. Particularly,
      a three-day continuous extension is sufficient to suppress the epidemic and
      confine the spread of disease. For the pandemic flu, the weekend-extension
      strategies only produce a few mitigation effects until the extensions exceed
      three days. Sensitivity analysis indicated that a compliance level above 75% is
      necessary for the weekend-extension strategies to take effects. CONCLUSION: This
      research is the first attempt to incorporate the weekend effect into influenza
      mitigation strategies. The results suggest that appropriate extensions of the
      regular two-day weekend can be a potential measure to fight against influenza
      outbreaks, while minimizing interruptions on normal rhythms of socio-economy. The
      concept of weekend extension would be particularly useful if there were a lack of
      vaccine stockpiles, e.g., in countries with limited health resources, or in the
      case of unknown emerging infectious diseases.

PMID- 21718519
TI  - Reproductive health and access to healthcare facilities: risk factors for
      depression and anxiety in women with an earthquake experience.
AB  - BACKGROUND: The reproductive and mental health of women contributes significantly
      to their overall well-being. Three of the eight Millennium Development Goals are
      directly related to reproductive and sexual health while mental disorders make up
      three of the ten leading causes of disease burden in low and middle-income
      countries. Among mental disorders, depression and anxiety are two of the most
      prevalent. In the context of slower progress in achieving Millennium Development
      Goals in developing countries and the ever-increasing man-made and natural
      disasters in these areas, it is important to understand the association between
      reproductive health and mental health among women with post-disaster experiences.
      METHODS: This was a cross-sectional study with a sample of 387 women of
      reproductive age (15-49 years) randomly selected from the October 2005 earthquake
      affected areas of Pakistan. Data on reproductive health was collected using the
      Centers for Disease Control reproductive health assessment toolkit. Depression
      and anxiety were measured using the Hopkins Symptom Checklist-25, while
      earthquake experiences were captured using the Harvard Trauma Questionnaire. The
      association of either depression or anxiety with socio-demographic variables,
      earthquake experiences, reproductive health and access to health facilities was
      estimated using multivariate logistic regression. RESULTS: Post-earthquake
      reproductive health events together with economic deprivation, lower family
      support and poorer access to health care facilities explained a significant
      proportion of differences in the experiencing of clinical levels of depression
      and anxiety. For instance, women losing resources for subsistence, separation
      from family and experiencing reproductive health events such as having a
      stillbirth, having had an abortion, having had abnormal vaginal discharge or
      having had genital ulcers, were at significant risk of depression and anxiety.
      CONCLUSION: The relationship between women's post-earthquake mental health and
      reproductive health, socio-economic status, and health care access is complex and
      explained largely by the socio-cultural role of women. It is suggested that
      interventions that consider gender differences and that are culturally
      appropriate are likely to reduce the incidence.

PMID- 21718520
TI  - minSKIN does a multifaceted intervention improve the competence in the diagnosis
      of skin cancer by general practitioners? Study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: In Switzerland, skin cancer is one of the most common neoplasms.
      Melanoma is the most aggressive one and can be lethal if not detected and removed
      on time. Nonmelanoma skin cancer is more frequent as melanoma; it is seldom
      lethal but can disfigure patients in advanced stages. General practitioners (GPs)
      are often faced with suspicious skin lesions of their patients. METHODS/DESIGN: 
      DESIGN: Randomised controlled trial (RCT). POPULATION: 60 GPs, randomised into
      intervention group and control group. INTERVENTION: GPs get a Lumio loupe, a
      digital camera and continuous feedback based on pictures of skin lesions they
      send to the Dermatologist. PRIMARY OUTCOME: Competence in the diagnosis of skin
      cancer by GPs, measured as the percentage of correctly classified pictures of
      skin lesions. MEASUREMENTS: At baseline, and prior to any intervention (T0), GPs
      will be asked to rate 36 pictures of skin lesions according to their likelihood
      of malignancy on a visual analogue scale (VAS). After a full day training course
      with both groups (T1) and after one year of continuous feedback (T2) with the
      intervention group, we will repeat the picture scoring session with both groups,
      using new pictures. DISCUSSION: We want to determine whether a multifaceted
      intervention (including technical equipment and a continuous feedback on skin
      lesions) leads to an improved competence in the diagnosis of skin cancer by GPs.
      This study addresses the hypothesis that an additional feedback loop, based on
      pictures performed in daily practice by GPs is superior to a simple educational
      intervention regarding diagnostic competence. We expect an improvement of the
      competence in skin cancer diagnosis by GPs in both groups after the full day
      training course. Beside this immediate effect, we also expect a long term effect
      in the intervention group because of the continuous problem based feedback. TRIAL
      REGISTRATION:  ISRCTN: ISRCTN29854485.

PMID- 21718521
TI  - Comparison of buccal and blood-derived canine DNA, either native or whole genome
      amplified, for array-based genome-wide association studies.
AB  - BACKGROUND: The availability of array-based genotyping platforms for single
      nucleotide polymorphisms (SNPs) for the canine genome has expanded the
      opportunities to undertake genome-wide association (GWA) studies to identify the
      genetic basis for Mendelian and complex traits. Whole blood as the source of high
      quality DNA is undisputed but often proves impractical for collection of the
      large numbers of samples necessary to discover the loci underlying complex
      traits. Further, many countries prohibit the collection of blood from dogs unless
      medically necessary thereby restricting access to critical control samples from
      healthy dogs. Alternate sources of DNA, typically from buccal cytobrush
      extractions, while convenient, have been suggested to have low yield and perform
      poorly in GWA. Yet buccal cytobrushes provide a cost-effective means of
      collecting DNA, are readily accepted by dog owners, and represent a large
      resource base in many canine genetics laboratories. To increase the DNA
      quantities, whole genome amplification (WGA) can be performed. Thus, the present
      study assessed the utility of buccal-derived DNA as well as whole genome
      amplification in comparison to blood samples for use on the most recent iteration
      of the canine HD SNP array (Illumina). FINDINGS: In both buccal and blood
      samples, whether whole genome amplified or not, 97% of the samples had SNP call
      rates in excess of 80% indicating that the vast majority of the SNPs would be
      suitable to perform association studies regardless of the DNA source. Similarly,
      there were no significant differences in marker intensity measurements between
      buccal and blood samples for copy number variations (CNV) analysis. CONCLUSIONS:
      All DNA samples assayed, buccal or blood, native or whole genome amplified, are
      appropriate for use in array-based genome-wide association studies. The
      concordance between subsets of dogs for which both buccal and blood samples, or
      those samples whole genome amplified, was shown to average >99%. Thus, the two
      DNA sources were comparable in the generation of SNP genotypes and intensity
      values to estimate structural variation indicating the utility for the use of
      buccal cytobrush samples and the reliability of whole genome amplification for
      genome-wide association and CNV studies.

PMID- 21718522
TI  - Safety and efficacy of miltefosine alone and in combination with sodium
      stibogluconate and liposomal amphotericin B for the treatment of primary visceral
      leishmaniasis in East Africa: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Treatment options for visceral leishmaniasis (VL) in East Africa are
      far from satisfactory due to cost, toxicity, prolonged treatment duration or
      emergence of parasite resistance. Hence there is a need to explore alternative
      treatment protocols such as miltefosine alone or in combinations including
      miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of
      this trial is to identify regimen(s) which are sufficiently promising for future
      trials in East Africa. METHODS/DESIGN: A phase II randomized, parallel arm, open
      labelled trial is being conducted to assess the efficacy of each of the three
      regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with
      miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with
      secondary endpoint at day 210 (6 months). Initial cure is a single composite
      measure based on parasitologic evaluation (bone marrow, spleen or lymph node
      aspirate) and clinical assessment. Repeated interim analyses have been planned
      after recruitment of 15 patients in each arm with a maximum sample size of 63 for
      each. These will follow group-sequential methods (the triangular test) to
      identify when a regimen is inadequate (<75% efficacy) or adequate (>90%
      efficacy). We describe a method to ensure consistency of the sequential analysis
      of day 28 cure with the non-sequential analysis of day 210 cure. DISCUSSION: A
      regimen with adequate efficacy would be a candidate for treatment of VL with
      reasonable costs. The design allows repeated testing throughout the trial
      recruitment period while maintaining good statistical properties (Type I & II
      error rates) and reducing the expected sample sizes. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01067443.

PMID- 21718523
TI  - Experiences of guided Internet-based cognitive-behavioural treatment for
      depression: a qualitative study.
AB  - BACKGROUND: Internet-based self-help treatment with minimal therapist contact has
      been shown to have an effect in treating various conditions. The objective of
      this study was to explore participants' views of Internet administrated guided
      self-help treatment for depression. METHODS: In-depth interviews were conducted
      with 12 strategically selected participants and qualitative methods with
      components of both thematic analysis and grounded theory were used in the
      analyses. RESULTS: Three distinct change processes relating to how participants
      worked with the treatment material emerged which were categorized as (a) Readers,
      (b) Strivers, and (c) Doers. These processes dealt with attitudes towards
      treatment, views on motivational aspects of the treatment, and perceptions of
      consequences of the treatment. CONCLUSIONS: We conclude that the findings
      correspond with existing theoretical models of face-to-face psychotherapy within
      qualitative process research. Persons who take responsibility for the treatment
      and also attribute success to themselves appear to benefit more. Motivation is a
      crucial aspect of guided self-help in the treatment of depression.

PMID- 21718524
TI  - Uptake of family planning methods and unplanned pregnancies among HIV-infected
      individuals: a cross-sectional survey among clients at HIV clinics in Uganda.
AB  - BACKGROUND: Prevention of unplanned pregnancies among HIV-infected individuals is
      critical to the prevention of mother to child HIV transmission (PMTCT), but its
      potential has not been fully utilized by PMTCT programmes. The uptake of family
      planning methods among women in Uganda is low, with current use of family
      planning methods estimated at 24%, but available data has not been disaggregated
      by HIV status. The aim of this study was to assess the utilization of family
      planning and unintended pregnancies among HIV-infected people in Uganda. METHODS:
      We conducted exit interviews with 1100 HIV-infected individuals, including 441
      men and 659 women, from 12 HIV clinics in three districts in Uganda to assess the
      uptake of family planning services, and unplanned pregnancies, among HIV-infected
      people. We conducted multivariate analysis for predictors of current use of
      family planning among women who were married or in consensual union and were not
      pregnant at the time of the interview. RESULTS: One-third (33%, 216) of the women
      reported being pregnant since their HIV diagnoses and 28% (123) of the men
      reported their partner being pregnant since their HIV diagnoses. Of these, 43%
      (105) said these pregnancies were not planned: 53% (80) among women compared with
      26% (25) among men. Most respondents (58%; 640) reported that they were currently
      using family planning methods. Among women who were married or in consensual
      union and not pregnant, 80% (242) were currently using any family planning method
      and 68% were currently using modern family planning methods (excluding
      withdrawal, lactational amenorrhoea and rhythm). At multivariate analysis, women
      who did not discuss the number of children they wanted with their partners and
      those who did not disclose their HIV status to sexual partners were less likely
      to use modern family planning methods (adjusted OR 0.40, range 0.20-0.81, and
      0.30, range 0.10-0.85, respectively). CONCLUSIONS: The uptake of family planning
      among HIV-infected individuals is fairly high. However, there are a large number
      of unplanned pregnancies. These findings highlight the need for strengthening of
      family planning services for HIV-infected people.

PMID- 21718525
TI  - Differences in pain, function and coping in Multidimensional Pain Inventory
      subgroups of chronic back pain: a one-group pretest-posttest study.
AB  - BACKGROUND: Patients with non-specific back pain are not a homogeneous group but
      heterogeneous with regard to their bio-psycho-social impairments. This study
      examined a sample of 173 highly disabled patients with chronic back pain to find
      out how the three subgroups based on the Multidimensional Pain Inventory (MPI)
      differed in their response to an inpatient pain management program. METHODS:
      Subgroup classification was conducted by cluster analysis using MPI subscale
      scores at entry into the program. At program entry and at discharge after four
      weeks, participants completed the MPI, the MOS Short Form-36 (SF-36), the
      Hospital Anxiety and Depression Scale (HADS), and the Coping Strategies
      Questionnaire (CSQ). Pairwise analyses of the score changes of the mentioned
      outcomes of the three MPI subgroups were performed using the Mann-Whitney-U-test
      for significance. RESULTS: Cluster analysis identified three MPI subgroups in
      this highly disabled sample: a dysfunctional, interpersonally distressed and an
      adaptive copers subgroup. The dysfunctional subgroup (29% of the sample) showed
      the highest level of depression in SF-36 mental health (33.4 +/- 13.9), the
      interpersonally distressed subgroup (35% of the sample) a modest level of
      depression (46.8 +/- 20.4), and the adaptive copers subgroup (32% of the sample)
      the lowest level of depression (57.8 +/- 19.1). Significant differences in pain
      reduction and improvement of mental health and coping were observed across the
      three MPI subgroups, i.e. the effect sizes for MPI pain reduction were: 0.84
      (0.44-1.24) for the dysfunctional subgroup, 1.22 (0.86-1.58) for the adaptive
      copers subgroup, and 0.53 (0.24-0.81) for the interpersonally distressed subgroup
      (p = 0.006 for pairwise comparison). Significant score changes between subgroups
      concerning activities and physical functioning could not be identified.
      CONCLUSIONS: MPI subgroup classification showed significant differences in score
      changes for pain, mental health and coping. These findings underscore the
      importance of assessing individual differences to understand how patients adjust
      to chronic back pain.

PMID- 21718526
TI  - Helplessness and perceived pain intensity: relations to cortisol concentrations
      after electrocutaneous stimulation in healthy young men.
AB  - BACKGROUND: Uncontrollable aversive events are associated with feelings of
      helplessness and cortisol elevation and are suitable as a model of depression.
      The high comorbidity of depression and pain symptoms and the importance of
      controllability in both conditions are clinically well-known but empirical
      studies are scarce. The study investigated the relationship of pain experience,
      helplessness, and cortisol secretion after controllable vs. uncontrollable
      electric skin stimulation in healthy male individuals. METHODS: Sixty-four male
      volunteers were randomly assigned to receive 30 controllable (self-administered)
      or uncontrollable (experimenter-administered) painful electric skin stimuli.
      Perceived pain intensity (PPI), subjective helplessness ratings, and salivary
      cortisol concentrations were assessed. PPI was assessed after stress exposure.
      For salivary cortisol concentrations and subjective helplessness ratings, areas
      under the response curve (AUC) were calculated. RESULTS: After uncontrollable vs.
      controllable stress exposure significantly higher PPI ratings (P = 0.023), higher
      subjective helplessness AUC (P < 0.0005) and higher salivary cortisol AUC (P =
      0.004, t-tests) were found. Correlation analyses revealed a significant
      correlation between subjective helplessness AUC and PPI (r = 0.500, P < 0.0005),
      subjective helplessness AUC and salivary cortisol AUC (r = 0.304, P = 0.015) and
      between PPI and salivary cortisol AUC (r = 0.298, P = 0.017). CONCLUSIONS: The
      results confirm the impact of uncontrollability on stress responses in humans;
      the relationship of PPI with subjective helplessness and salivary cortisol
      suggests a cognitive-affective sensitization of pain perception, particularly
      under uncontrollable conditions.

PMID- 21718527
TI  - Identification and characterization of microRNAs from Phaeodactylum tricornutum
      by high-throughput sequencing and bioinformatics analysis.
AB  - BACKGROUND: Diatoms, which are important planktons widespread in various aquatic
      environments, are believed to play a vital role in primary production as well as
      silica cycling. The genomes of the pennate diatom Phaeodactylum tricornutum and
      the centric diatom Thalassiosira pseudonana have been sequenced, revealing some
      characteristics of the diatoms' mosaic genome as well as some features of their
      fatty acid metabolism and urea cycle, and indicating their unusual properties. To
      identify microRNAs (miRNAs) from P. tricornutum and to study their probable roles
      in nitrogen and silicon metabolism, we constructed and sequenced small RNA (sRNA)
      libraries from P. tricornutum under normal (PT1), nitrogen-limited (PT2) and
      silicon-limited (PT3) conditions. RESULTS: A total of 13 miRNAs were identified.
      They were probable P. tricornutum-specific novel miRNAs. These miRNAs were
      sequenced from P. tricornutum under normal, nitrogen-limited and/or silicon
      limited conditions, and their potential targets were involved in various
      processes, such as signal transduction, protein amino acid phosphorylation, fatty
      acid biosynthetic process, regulation of transcription and so on. CONCLUSIONS:
      Our results indicated that P. tricornutum contained novel miRNAs that have no
      identifiable homologs in other organisms and that they might play important
      regulator roles in P. tricornutum metabolism.

PMID- 21718528
TI  - Blunting type 1 insulin-like growth factor receptor expression exacerbates
      neuronal apoptosis following hypoxic/ischemic injury.
AB  - BACKGROUND: Abundant experimental data have implicated an important role for
      insulin-like growth factor (IGF) in protecting neuronal cells from injury,
      including hypoxia/ischemia (H/I) injury, a major cause of neuron death. While the
      specific interaction of IGFs with neuronal or glial type 1 IGF receptors (IGF1R)
      has been shown to be essential to IGF actions during development, the same has
      not been directly demonstrated following H/I injury. To directly examine the role
      of neuronal IGF1R following H/I injury, we utilized conditional mutant nes-igf1r(
      /Wt) mice and determined the impact of IGF1R haplodeficiency specifically in
      nestin-expressing neuronal precursors and their progeny on H/I-induced neuronal
      damage and apoptosis in hippocampus. RESULTS: H/I induced significant damage to
      the cerebral hemisphere and hippocampus ipsilateral to the ligated right common
      carotid artery both in control and nes-igf1r(-/Wt) mice at postnatal day 10.
      Blunting IGF1R expression, however, markedly exacerbated H/I-induced damage and
      appeared to increase mortality. In the ipsilateral hemisphere and hippocampus,
      nes-igf1r(-/Wt) mice had infarct areas double the size of those in controls. The
      size of the ipsilateral hemisphere and hippocampus in nes-igf1r(-/Wt) mice were
      15% to 17% larger than those in controls, reflecting more severe edema.
      Consistent with its effects on infarct area, IGF1R haplodeficiency causes a
      greater decrease in neurons in the ipsilateral hippocampus of nes-igf1r(-/Wt)
      mice. The reduction in neurons was largely due to increases in neuronal
      apoptosis. Judged by pyknotic nuclei, TUNEL and caspase-3 labeling, nes-igf1r(
      /Wt) mice had significantly more apoptotic cells than that in controls after
      injury. To determine possible mechanisms of IGF1R actions, the mRNA expression of
      the pro-survival proteins IAP-1 and XIAP was determined. Compared to controls,
      the abundance of cIAP-1 and XIAP mRNA was markedly suppressed in mice with
      blunted IGF1R or IGF-I expression, while was increased in the brain of IGF-I
      overexpressing transgenic mice. CONCLUSION: IGF1R in neuronal cells is critically
      important for their survival following H/I injury, and IGF-upregulated expression
      of neuronal cIAP-1 and XIAP likely in part contributes to IGF-IGF1R protection
      against neuronal apoptosis following H/I injury.

PMID- 21718529
TI  - Elemental analysis of lung tissue particles and intracellular iron content of
      alveolar macrophages in pulmonary alveolar proteinosis.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease occurred by
      idiopathic (autoimmune) or secondary to particle inhalation. The in-air
      microparticle induced X-ray emission (in-air micro-PIXE) system performs
      elemental analysis of materials by irradiation with a proton microbeam, and
      allows visualization of the spatial distribution and quantitation of various
      elements with very low background noise. The aim of this study was to assess the
      secondary PAP due to inhalation of harmful particles by employing in-air micro
      PIXE analysis for particles and intracellular iron in parafin-embedded lung
      tissue specimens obtained from a PAP patient comparing with normal lung tissue
      from a non-PAP patient. The iron inside alveolar macrophages was stained with
      Berlin blue, and its distribution was compared with that on micro-PIXE images.
      RESULTS: The elements composing particles and their locations in the PAP
      specimens could be identified by in-air micro-PIXE analysis, with magnesium (Mg),
      aluminum (Al), silicon (Si), phosphorus (P), sulfur (S), scandium (Sc), potassium
      (K), calcium (Ca), titanium (Ti), chromium (Cr), copper (Cu), manganase (Mn),
      iron (Fe), and zinc (Zn) being detected. Si was the major component of the
      particles. Serial sections stained by Berlin blue revealed accumulation of
      sideromacrophages that had phagocytosed the particles. The intracellular iron
      content of alveolar macrophage from the surfactant-rich area in PAP was higher
      than normal lung tissue in control lung by both in-air micro-PIXE analysis and
      Berlin blue staining. CONCLUSION: The present study demonstrated the efficacy of
      in-air micro-PIXE for analyzing the distribution and composition of lung
      particles. The intracellular iron content of single cells was determined by
      simultaneous two-dimensional and elemental analysis of paraffin-embedded lung
      tissue sections. The results suggest that secondary PAP is associated with
      exposure to inhaled particles and accumulation of iron in alveolar macrophages.

PMID- 21718530
TI  - Sample size calculations for cluster randomised controlled trials with a fixed
      number of clusters.
AB  - BACKGROUND: Cluster randomised controlled trials (CRCTs) are frequently used in
      health service evaluation. Assuming an average cluster size, required sample
      sizes are readily computed for both binary and continuous outcomes, by estimating
      a design effect or inflation factor. However, where the number of clusters are
      fixed in advance, but where it is possible to increase the number of individuals
      within each cluster, as is frequently the case in health service evaluation,
      sample size formulae have been less well studied. METHODS: We systematically
      outline sample size formulae (including required number of randomisation units,
      detectable difference and power) for CRCTs with a fixed number of clusters, to
      provide a concise summary for both binary and continuous outcomes. Extensions to
      the case of unequal cluster sizes are provided. RESULTS: For trials with a fixed
      number of equal sized clusters (k), the trial will be feasible provided the
      number of clusters is greater than the product of the number of individuals
      required under individual randomisation (nI) and the estimated intra-cluster
      correlation (rho). So, a simple rule is that the number of clusters (k) will be
      sufficient provided: [formula in text]. Where this is not the case, investigators
      can determine the maximum available power to detect the pre-specified difference,
      or the minimum detectable difference under the pre-specified value for power.
      CONCLUSIONS: Designing a CRCT with a fixed number of clusters might mean that the
      study will not be feasible, leading to the notion of a minimum detectable
      difference (or a maximum achievable power), irrespective of how many individuals
      are included within each cluster.

PMID- 21718531
TI  - Harm reduction, methadone maintenance treatment and the root causes of health and
      social inequities: An intersectional lens in the Canadian context.
AB  - BACKGROUND: Using our research findings, we explore Harm Reduction and Methadone
      Maintenance Treatment (MMT) using an intersectional lens to provide a more
      complex understanding of Harm Reduction and MMT, particularly how Harm Reduction
      and MMT are experienced differently by people dependent on how they are
      positioned. Using the lens of intersectionality, we refine the notion of Harm
      Reduction by specifying the conditions in which both harm and benefit arise and
      how experiences of harm are continuous with wider experiences of domination and
      oppression; METHODS: A qualitative design that uses ethnographic methods of in
      depth individual and focus group interviews and naturalistic observation was
      conducted in a large city in Canada. Participants included Aboriginal clients
      accessing mainstream mental health and addictions care and primary health care
      settings and healthcare providers; RESULTS: All client-participants had profound
      histories of abuse and violence, most often connected to the legacy of
      colonialism (e.g., residential schooling) and ongoing colonial practices (e.g.,
      stigma & everyday racism). Participants lived with co-occurring illness (e.g.,
      HIV/AIDS, Hepatitis C, PTSD, depression, diabetes and substance use) and most
      lived in poverty. Many participants expressed mistrust with the healthcare system
      due to everyday experiences both within and outside the system that further
      marginalize them. In this paper, we focus on three intersecting issues that
      impact access to MMT: stigma and prejudice, social and structural constraints
      influencing enactment of peoples' agency, and homelessness; CONCLUSIONS: Harm
      reduction must move beyond a narrow concern with the harms directly related to
      drugs and drug use practices to address the harms associated with the
      determinants of drug use and drug and health policy. An intersectional lens
      elucidates the need for harm reduction approaches that reflect an understanding
      of and commitment to addressing the historical, socio-cultural and political
      forces that shape responses to mental illness/health, addictions, including harm
      reduction and methadone maintenance treatment.

PMID- 21718532
TI  - The role of Cra in regulating acetate excretion and osmotic tolerance in E. coli
      K-12 and E. coli B at high density growth.
AB  - BACKGROUND: E. coli B (BL21), unlike E.coli K-12 (JM109) is insensitive to
      glucose concentration and, therefore, grows faster and produces less acetate than
      E. coli K-12, especially when growing to high cell densities at high glucose
      concentration. By performing genomic analysis, it was demonstrated that the cause
      of this difference in sensitivity to the glucose concentration is the result of
      the differences in the central carbon metabolism activity. We hypothesized that
      the global transcription regulator Cra (FruR) is constitutively expressed in E.
      coli B and may be responsible for the different behaviour of the two strains. To
      investigate this possibility and better understand the function of Cra in the two
      strains, cra - negative E. coli B (BL21) and E. coli K-12 (JM109) were prepared
      and their growth behaviour and gene expression at high glucose were evaluated
      using microarray and real-time PCR. RESULTS: The deletion of the cra gene in E.
      coli B (BL21) minimally affected the growth and maximal acetate accumulation,
      while the deletion of the same gene in E.coli K-12 (JM109) caused the cells to
      stop growing as soon as acetate concentration reached 6.6 g/L and the media
      conductivity reached 21 mS/cm. ppsA (gluconeogenesis gene), aceBA (the glyoxylate
      shunt genes) and poxB (the acetate producing gene) were down-regulated in both
      strains, while acs (acetate uptake gene) was down-regulated only in E.coli B
      (BL21). These transcriptional differences had little effect on acetate and
      pyruvate production. Additionally, it was found that the lower growth of E. coli
      K-12 (JM109) strain was the result of transcription inhibition of the
      osmoprotectant producing bet operon (betABT). CONCLUSIONS: The transcriptional
      changes caused by the deletion of cra gene did not affect the activity of the
      central carbon metabolism, suggesting that Cra does not act alone; rather it
      interacts with other pleiotropic regulators to create a network of metabolic
      effects. An unexpected outcome of this work is the finding that cra deletion
      caused transcription inhibition of the bet operon in E. coli K-12 (JM109) but did
      not affect this operon transcription in E. coli B (BL21). This property, together
      with the insensitivity to high glucose concentrations, makes this the E. coli B
      (BL21) strain more resistant to environmental changes.

PMID- 21718533
TI  - Design of a variant surface antigen-supplemented microarray chip for whole
      transcriptome analysis of multiple Plasmodium falciparum cytoadherent strains,
      and identification of strain-transcendent rif and stevor genes.
AB  - BACKGROUND: The cytoadherence of Plasmodium falciparum is thought to be mediated
      by variant surface antigens (VSA), encoded by var, rif, stevor and pfmc-2tm
      genes. The last three families have rarely been studied in the context of
      cytoadherence. As most VSA genes are unique, the variability among sequences has
      impeded the functional study of VSA across different P. falciparum strains.
      However, many P. falciparum genomes have recently been sequenced, allowing the
      development of specific microarray probes for each VSA gene. METHODS: All VSA
      sequences from the HB3, Dd2 and IT/FCR3 genomes were extracted using HMMer
      software. Oligonucleotide probes were designed with OligoRankPick and added to
      the 3D7-based microarray chip. As a proof of concept, IT/R29 parasites were
      selected for and against rosette formation and the transcriptomes of isogenic
      rosetting and non-rosetting parasites were compared by microarray. RESULTS: From
      each parasite strain 50-56 var genes, 125-132 rif genes, 26-33 stevor genes and 3
      8 pfmc-2tm genes were identified. Bioinformatic analysis of the new VSA sequences
      showed that 13 rif genes and five stevor genes were well-conserved across at
      least three strains (83-100% amino acid identity). The ability of the VSA
      supplemented microarray chip to detect cytoadherence-related genes was assessed
      using P. falciparum clone IT/R29, in which rosetting is known to be mediated by
      PfEMP1 encoded by ITvar9. Whole transcriptome analysis showed that the most
      highly up-regulated gene in rosetting parasites was ITvar9 (19 to 429-fold up
      regulated over six time points). Only one rif gene (IT4rifA_042) was up-regulated
      by more than four fold (five fold at 12 hours post-invasion), and no stevor or
      pfmc-2tm genes were up-regulated by more than two fold. 377 non-VSA genes were
      differentially expressed by three fold or more in rosetting parasites, although
      none was as markedly or consistently up-regulated as ITvar9. CONCLUSIONS: Probes
      for the VSA of newly sequenced P. falciparum strains can be added to the 3D7
      based microarray chip, allowing the analysis of the entire transcriptome of
      multiple strains. For the rosetting clone IT/R29, the striking transcriptional
      upregulation of ITvar9 was confirmed, and the data did not support the
      involvement of other VSA families in rosette formation.

PMID- 21718534
TI  - CANGS DB: a stand-alone web-based database tool for processing, managing and
      analyzing 454 data in biodiversity studies.
AB  - BACKGROUND: Next generation sequencing (NGS) is widely used in metagenomic and
      transcriptomic analyses in biodiversity. The ease of data generation provided by
      NGS platforms has allowed researchers to perform these analyses on their
      particular study systems. In particular the 454 platform has become the preferred
      choice for PCR amplicon based biodiversity surveys because it generates the
      longest sequence reads. Nevertheless, the handling and organization of massive
      amounts of sequencing data poses a major problem for the research community,
      particularly when multiple researchers are involved in data acquisition and
      analysis. An integrated and user-friendly tool, which performs quality control,
      read trimming, PCR primer removal, and data organization is desperately needed,
      therefore, to make data interpretation fast and manageable. FINDINGS: We
      developed CANGS DB (Cleaning and Analyzing Next Generation Sequences DataBase) a
      flexible, stand alone and user-friendly integrated database tool. CANGS DB is
      specifically designed to organize and manage the massive amount of sequencing
      data arising from various NGS projects. CANGS DB also provides an intuitive user
      interface for sequence trimming and quality control, taxonomy analysis and
      rarefaction analysis. Our database tool can be easily adapted to handle multiple
      sequencing projects in parallel with different sample information, amplicon
      sizes, primer sequences, and quality thresholds, which makes this software
      especially useful for non-bioinformaticians. Furthermore, CANGS DB is especially
      suited for projects where multiple users need to access the data. CANGS DB is
      available at http://code.google.com/p/cangsdb/. CONCLUSION: CANGS DB provides a
      simple and user-friendly solution to process, store and analyze 454 sequencing
      data. Being a local database that is accessible through a user-friendly
      interface, CANGS DB provides the perfect tool for collaborative amplicon based
      biodiversity surveys without requiring prior bioinformatics skills.

PMID- 21718535
TI  - Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in
      vitro.
AB  - BACKGROUND: To study the effects of zoledronic acid (ZA) on the vasculogenic
      mimicry of osteosarcoma cells in vitro. METHODS: A Three-dimensional culture of
      LM8 osteosarcoma cells on a type I collagen matrix was used to investigate
      whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the
      effects of ZA on this process. In addition, the cellular ultrastructural changes
      were observed using scanning electron microscopy and laser confocal microscopy.
      The effects of ZA on the translocation of RhoA protein from the cytosol to the
      membrane in LM8 cells were measured via immunoblotting. RESULTS: ZA inhibited the
      development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased
      microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton.
      ZA prevented translocation of RhoA protein from the cytosol to the membrane in
      LM8 cells. CONCLUSIONS: ZA can impair RhoA membrane localization in LM8 cells,
      causing obvious changes in the ultrastructure of osteosarcoma cells and induce
      cell apoptosis, which may be one of the underlying mechanisms by which the agent
      inhibits the development of vasculogenic mimicry by the LM8 cells.

PMID- 21718536
TI  - Genome Wide Association Study to predict severe asthma exacerbations in children
      using random forests classifiers.
AB  - BACKGROUND: Personalized health-care promises tailored health-care solutions to
      individual patients based on their genetic background and/or environmental
      exposure history. To date, disease prediction has been based on a few
      environmental factors and/or single nucleotide polymorphisms (SNPs), while
      complex diseases are usually affected by many genetic and environmental factors
      with each factor contributing a small portion to the outcome. We hypothesized
      that the use of random forests classifiers to select SNPs would result in an
      improved predictive model of asthma exacerbations. We tested this hypothesis in a
      population of childhood asthmatics. METHODS: In this study, using emergency room
      visits or hospitalizations as the definition of a severe asthma exacerbation, we
      first identified a list of top Genome Wide Association Study (GWAS) SNPs ranked
      by Random Forests (RF) importance score for the CAMP (Childhood Asthma Management
      Program) population of 127 exacerbation cases and 290 non-exacerbation controls.
      We predict severe asthma exacerbations using the top 10 to 320 SNPs together with
      age, sex, pre-bronchodilator FEV1 percentage predicted, and treatment group.
      RESULTS: Testing in an independent set of the CAMP population shows that severe
      asthma exacerbations can be predicted with an Area Under the Curve (AUC)=0.66
      with 160-320 SNPs in comparison to an AUC score of 0.57 with 10 SNPs. Using the
      clinical traits alone yielded AUC score of 0.54, suggesting the phenotype is
      affected by genetic as well as environmental factors. CONCLUSIONS: Our study
      shows that a random forests algorithm can effectively extract and use the
      information contained in a small number of samples. Random forests, and other
      machine learning tools, can be used with GWAS studies to integrate large numbers
      of predictors simultaneously.

PMID- 21718537
TI  - Optimizing HIV-1 protease production in Escherichia coli as fusion protein.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) is the etiological agent in AIDS
      and related diseases. The aspartyl protease encoded by the 5' portion of the pol
      gene is responsible for proteolytic processing of the gag-pol polyprotein
      precursor to yield the mature capsid protein and the reverse transcriptase and
      integrase enzymes. The HIV protease (HIV-1Pr) is considered an attractive target
      for designing inhibitors which could be used to tackle AIDS and therefore it is
      still the object of a number of investigations. RESULTS: A recombinant human
      immunodeficiency virus type 1 protease (HIV-1Pr) was overexpressed in Escherichia
      coli cells as a fusion protein with bacterial periplasmic protein dithiol oxidase
      (DsbA) or glutathione S-transferase (GST), also containing a six-histidine tag
      sequence. Protein expression was optimized by designing a suitable HIV-1Pr cDNA
      (for E. coli expression and to avoid autoproteolysis) and by screening six
      different E. coli strains and five growth media. The best expression yields were
      achieved in E. coli BL21-Codon Plus(DE3)-RIL host and in TB or M9 medium to which
      1% (w/v) glucose was added to minimize basal expression. Among the different
      parameters assayed, the presence of a buffer system (based on phosphate salts)
      and a growth temperature of 37 degrees C after adding IPTG played the main role
      in enhancing protease expression (up to 10 mg of chimeric DsbA:HIV-1Pr/L
      fermentation broth). GST:HIVPr was in part (50%) produced as soluble protein
      while the overexpressed DsbA:HIV-1Pr chimeric protein largely accumulated in
      inclusion bodies as unprocessed fusion protein. A simple refolding procedure was
      developed on HiTrap Chelating column that yielded a refolded DsbA:HIV-1Pr with a
      > 80% recovery. Finally, enterokinase digestion of resolubilized DsbA:HIV-1Pr
      gave more than 2 mg of HIV-1Pr per liter of fermentation broth with a purity <=
      80%, while PreScission protease cleavage of soluble GST:HIVPr yielded ~ 0.15 mg
      of pure HIV-1Pr per liter. CONCLUSIONS: By using this optimized expression and
      purification procedure fairly large amounts of good-quality HIV-1Pr recombinant
      enzyme can be produced at the lab-scale and thus used for further biochemical
      studies.

PMID- 21718538
TI  - DNACLUST: accurate and efficient clustering of phylogenetic marker genes.
AB  - BACKGROUND: Clustering is a fundamental operation in the analysis of biological
      sequence data. New DNA sequencing technologies have dramatically increased the
      rate at which we can generate data, resulting in datasets that cannot be
      efficiently analyzed by traditional clustering methods.This is particularly true
      in the context of taxonomic profiling of microbial communities through direct
      sequencing of phylogenetic markers (e.g. 16S rRNA) - the domain that motivated
      the work described in this paper. Many analysis approaches rely on an initial
      clustering step aimed at identifying sequences that belong to the same
      operational taxonomic unit (OTU). When defining OTUs (which have no universally
      accepted definition), scientists must balance a trade-off between computational
      efficiency and biological accuracy, as accurately estimating an environment's
      phylogenetic composition requires computationally-intensive analyses. We propose
      that efficient and mathematically well defined clustering methods can benefit
      existing taxonomic profiling approaches in two ways: (i) the resulting clusters
      can be substituted for OTUs in certain applications; and (ii) the clustering
      effectively reduces the size of the data-sets that need to be analyzed by complex
      phylogenetic pipelines (e.g., only one sequence per cluster needs to be provided
      to downstream analyses). RESULTS: To address the challenges outlined above, we
      developed DNACLUST, a fast clustering tool specifically designed for clustering
      highly-similar DNA sequences.Given a set of sequences and a sequence similarity
      threshold, DNACLUST creates clusters whose radius is guaranteed not to exceed the
      specified threshold. Underlying DNACLUST is a greedy clustering strategy that
      owes its performance to novel sequence alignment and k-mer based filtering
      algorithms.DNACLUST can also produce multiple sequence alignments for every
      cluster, allowing users to manually inspect clustering results, and enabling more
      detailed analyses of the clustered data. CONCLUSIONS: We compare DNACLUST to two
      popular clustering tools: CD-HIT and UCLUST. We show that DNACLUST is about an
      order of magnitude faster than CD-HIT and UCLUST (exact mode) and comparable in
      speed to UCLUST (approximate mode). The performance of DNACLUST improves as the
      similarity threshold is increased (tight clusters) making it well suited for
      rapidly removing duplicates and near-duplicates from a dataset, thereby reducing
      the size of the data being analyzed through more elaborate approaches.

PMID- 21718539
TI  - Improving pan-genome annotation using whole genome multiple alignment.
AB  - BACKGROUND: Rapid annotation and comparisons of genomes from multiple isolates
      (pan-genomes) is becoming commonplace due to advances in sequencing technology.
      Genome annotations can contain inconsistencies and errors that hinder comparative
      analysis even within a single species. Tools are needed to compare and improve
      annotation quality across sets of closely related genomes. RESULTS: We introduce
      a new tool, Mugsy-Annotator, that identifies orthologs and evaluates annotation
      quality in prokaryotic genomes using whole genome multiple alignment. Mugsy
      Annotator identifies anomalies in annotated gene structures, including
      inconsistently located translation initiation sites and disrupted genes due to
      draft genome sequencing or pseudogenes. An evaluation of species pan-genomes
      using the tool indicates that such anomalies are common, especially at
      translation initiation sites. Mugsy-Annotator reports alternate annotations that
      improve consistency and are candidates for further review. CONCLUSIONS: Whole
      genome multiple alignment can be used to efficiently identify orthologs and
      annotation problem areas in a bacterial pan-genome. Comparisons of annotated gene
      structures within a species may show more variation than is actually present in
      the genome, indicating errors in genome annotation. Our new tool Mugsy-Annotator
      assists re-annotation efforts by highlighting edits that improve annotation
      consistency.

PMID- 21718540
TI  - All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved
      interactions with Vangl, Dvl, and serine/threonine kinases.
AB  - BACKGROUND: The Dact family of scaffold proteins was discovered by virtue of
      binding to Dvl proteins central to Wnt and Planar Cell Polarity (PCP) signaling.
      Subsequently Dact proteins have been linked to a growing list of potential
      partners implicated in beta-catenin-dependent and beta-catenin-independent forms
      of Wnt and other signaling. To clarify conserved and non-conserved roles for this
      protein family, we systematically compared molecular interactions of all three
      murine Dact paralogs by co-immunoprecipitation of proteins recombinantly
      expressed in cultured human embryonic kidney cells. RESULTS: Every Dact paralog
      readily formed complexes with the Vangl, Dvl, and CK1delta/epsilon proteins of
      species ranging from fruit flies to humans, as well as with PKA and PKC. Dact
      proteins also formed complexes with themselves and with each other; their
      conserved N-terminal leucine-zipper domains, which have no known binding
      partners, were necessary and sufficient for this interaction, suggesting that it
      reflects leucine-zipper-mediated homo- and hetero-dimerization. We also found
      weaker, though conserved, interactions of all three Dact paralogs with the
      catenin superfamily member p120ctn. Complex formation with other previously
      proposed partners including most other catenins, GSK3, LEF/TCF, HDAC1, and
      TGFbeta receptors was paralog-specific, comparatively weak, and/or more sensitive
      to empirical conditions. CONCLUSIONS: Combined with published functional evidence
      from targeted knock-out mice, these data support a conserved role for Dact
      proteins in kinase-regulated biochemistry involving Vangl and Dvl. This strongly
      suggests that a principal role for all Dact family members is in the PCP pathway
      or a molecularly related signaling cascade in vertebrates.

PMID- 21718541
TI  - Stroke with neuropsychiatric sequelae after cannabis use in a man: a case report.
AB  - INTRODUCTION: The outcome of cerebral ischemic stroke associated with cannabis
      use is usually favorable. Here we report the first case of cannabis-related
      stroke followed by neuropsychiatric sequelae. CASE PRESENTATION: A 24-year-old
      Caucasian man was discovered in a deeply comatose non-reactive state after
      cannabis use. A magnetic resonance imaging scan of his brain showed bilateral
      multiple ischemic infarcts. The patient remained deeply comatose for four days,
      after which time he developed other behavioral impairments and recurrent
      seizures. CONCLUSION: Stroke related to cannabis use can be followed by severe
      neuropsychiatric sequelae. Concomitant alcohol intoxication is essential neither
      to the occurrence of this neurologic event nor to its severity.

PMID- 21718542
TI  - Viewing medium affects arm motor performance in 3D virtual environments.
AB  - BACKGROUND: 2D and 3D virtual reality platforms are used for designing
      individualized training environments for post-stroke rehabilitation. Virtual
      environments (VEs) are viewed using media like head mounted displays (HMDs) and
      large screen projection systems (SPS) which can influence the quality of
      perception of the environment. We estimated if there were differences in arm
      pointing kinematics when subjects with and without stroke viewed a 3D VE through
      two different media: HMD and SPS. METHODS: Two groups of subjects participated
      (healthy control, n=10, aged 53.6 +/- 17.2 yrs; stroke, n=20, 66.2 +/- 11.3 yrs).
      Arm motor impairment and spasticity were assessed in the stroke group which was
      divided into mild (n=10) and moderate-to-severe (n=10) sub-groups based on Fugl
      Meyer Scores. Subjects pointed (8 times each) to 6 randomly presented targets
      located at two heights in the ipsilateral, middle and contralateral arm
      workspaces. Movements were repeated in the same VE viewed using HMD (Kaiser XL50)
      and SPS. Movement kinematics were recorded using an Optotrak system (Certus, 6
      markers, 100 Hz). Upper limb motor performance (precision, velocity, trajectory
      straightness) and movement pattern (elbow, shoulder ranges and trunk
      displacement) outcomes were analyzed using repeated measures ANOVAs. RESULTS: For
      all groups, there were no differences in endpoint trajectory straightness,
      shoulder flexion and shoulder horizontal adduction ranges and sagittal trunk
      displacement between the two media. All subjects, however, made larger errors in
      the vertical direction using HMD compared to SPS. Healthy subjects also made
      larger errors in the sagittal direction, slower movements overall and used less
      range of elbow extension for the lower central target using HMD compared to SPS.
      The mild and moderate-to-severe sub-groups made larger RMS errors with HMD. The
      only advantage of using the HMD was that movements were 22% faster in the
      moderate-to-severe stroke sub-group compared to the SPS. CONCLUSIONS: Despite the
      similarity in majority of the movement kinematics, differences in movement speed
      and larger errors were observed for movements using the HMD. Use of the SPS may
      be a more comfortable and effective option to view VEs for upper limb
      rehabilitation post-stroke. This has implications for the use of VR applications
      to enhance upper limb recovery.

PMID- 21718543
TI  - Screen-time weight-loss intervention targeting children at home (SWITCH): a
      randomized controlled trial study protocol.
AB  - BACKGROUND: Approximately one third of New Zealand children and young people are
      overweight or obese. A similar proportion (33%) do not meet recommendations for
      physical activity, and 70% do not meet recommendations for screen time. Increased
      time being sedentary is positively associated with being overweight. There are
      few family-based interventions aimed at reducing sedentary behavior in children.
      The aim of this trial is to determine the effects of a 24 week home-based, family
      oriented intervention to reduce sedentary screen time on children's body
      composition, sedentary behavior, physical activity, and diet. METHODS/DESIGN: The
      study design is a pragmatic two-arm parallel randomized controlled trial. Two
      hundred and seventy overweight children aged 9-12 years and primary caregivers
      are being recruited. Participants are randomized to intervention (family-based
      screen time intervention) or control (no change). At the end of the study, the
      control group is offered the intervention content. Data collection is undertaken
      at baseline and 24 weeks. The primary trial outcome is child body mass index
      (BMI) and standardized body mass index (zBMI). Secondary outcomes are change from
      baseline to 24 weeks in child percentage body fat; waist circumference; self
      reported average daily time spent in physical and sedentary activities; dietary
      intake; and enjoyment of physical activity and sedentary behavior. Secondary
      outcomes for the primary caregiver include change in BMI and self-reported
      physical activity. DISCUSSION: This study provides an excellent example of a
      theory-based, pragmatic, community-based trial targeting sedentary behavior in
      overweight children. The study has been specifically designed to allow for
      estimation of the consistency of effects on body composition for Maori
      (indigenous), Pacific and non-Maori/non-Pacific ethnic groups. If effective, this
      intervention is imminently scalable and could be integrated within existing
      weight management programs. TRIAL REGISTRATION: ACTRN12611000164998.

PMID- 21718544
TI  - The replication origin of a repABC plasmid.
AB  - BACKGROUND: repABC operons are present on large, low copy-number plasmids and on
      some secondary chromosomes in at least 19 alpha-proteobacterial genera, and are
      responsible for the replication and segregation properties of these replicons.
      These operons consist, with some variations, of three genes: repA, repB, and
      repC. RepA and RepB are involved in plasmid partitioning and in the negative
      regulation of their own transcription, and RepC is the limiting factor for
      replication. An antisense RNA encoded between the repB-repC genes modulates repC
      expression. RESULTS: To identify the minimal region of the Rhizobium etli p42d
      plasmid that is capable of autonomous replication, we amplified different regions
      of the repABC operon using PCR and cloned the regions into a suicide vector. The
      resulting vectors were then introduced into R. etli strains that did or did not
      contain p42d. The minimal replicon consisted of a repC open reading frame under
      the control of a constitutive promoter with a Shine-Dalgarno sequence that we
      designed. A sequence analysis of repC revealed the presence of a large A+T-rich
      region but no iterons or DnaA boxes. Silent mutations that modified the A+T
      content of this region eliminated the replication capability of the plasmid. The
      minimal replicon could not be introduced into R. etli strain containing p42d, but
      similar constructs that carried repC from Sinorhizobium meliloti pSymA or the
      linear chromosome of Agrobacterium tumefaciens replicated in the presence or
      absence of p42d, indicating that RepC is an incompatibility factor. A hybrid gene
      construct expressing a RepC protein with the first 362 amino acid residues from
      p42d RepC and the last 39 amino acid residues of RepC from SymA was able to
      replicate in the presence of p42d. CONCLUSIONS: RepC is the only element encoded
      in the repABC operon of the R. etli p42d plasmid that is necessary and sufficient
      for plasmid replication and is probably the initiator protein. The oriV of this
      plasmid resides within the repC gene and is located close to or inside of a large
      A+T region. RepC can act as an incompatibility factor, and the last 39 amino acid
      residues of the carboxy-terminal region of this protein are involved in promoting
      this phenotype.

PMID- 21718545
TI  - Effect of hosts on competition among clones and evidence of differential
      selection between pathogenic and saprophytic phases in experimental populations
      of the wheat pathogen Phaeosphaeria nodorum.
AB  - BACKGROUND: Monoculture, multi-cropping and wider use of highly resistant
      cultivars have been proposed as mechanisms to explain the elevated rate of
      evolution of plant pathogens in agricultural ecosystems. We used a mark-release
      recapture experiment with the wheat pathogen Phaeosphaeria nodorum to evaluate
      the impact of two of these mechanisms on the evolution of a pathogen population.
      Nine P. nodorum isolates marked with ten microsatellite markers and one
      minisatellite were released onto five replicated host populations to initiate
      epidemics of Stagonospora nodorum leaf blotch. The experiment was carried out
      over two consecutive host growing seasons and two pathogen collections were made
      during each season. RESULTS: A total of 637 pathogen isolates matching the marked
      inoculants were recovered from inoculated plots over two years. Genetic diversity
      in the host populations affected the evolution of the corresponding P. nodorum
      populations. In the cultivar mixture the relative frequencies of inoculants did
      not change over the course of the experiment and the pathogen exhibited a low
      variation in selection coefficients. CONCLUSIONS: Our results support the
      hypothesis that increasing genetic heterogeneity in host populations may retard
      the rate of evolution in associated pathogen populations. Our experiment also
      provides indirect evidence of fitness costs associated with host specialization
      in P. nodorum as indicated by differential selection during the pathogenic and
      saprophytic phases.

PMID- 21718546
TI  - Qualitative and quantitative research into the development and feasibility of a
      video-tailored physical activity intervention.
AB  - BACKGROUND: Continued low adherence to physical activity recommendations
      illustrates the need to refine intervention strategies and increase their
      effectiveness. The purpose of this study was to conduct formative research
      related to the development of a next generation of computer-tailored
      interventions that use online tailored video-messages to increase physical
      activity. METHODS: Five focus groups (n = 30), aimed at males and females, aged
      between 35 and 60 years, that do not meet the physical activity recommendation,
      were conducted to allow in-depth discussion of various elements related to the
      development of an online video-tailored intervention. In addition, a series of
      questions were delivered to a random sample (n = 1261) of Australians, using CATI
      survey technology, to gain more information and add a quantitative assessment of
      feasibility related to the development of the intervention. Focus group data was
      transcribed, and summarised using Nvivo software. Descriptive and frequency data
      of the survey was obtained using SPSS 18.0. RESULTS: Nearly all of the focus
      group participants supported the concept of a video-tailored intervention and
      35.8% of survey participants indicated that they would prefer a video-based over
      a text-based intervention. Participants with a slow internet-connection displayed
      a lower preference for video-based advice (31.9%); however less than 20% of the
      survey sample indicated that downloading videos would be slow. The majority of
      focus group and survey participants did not support the idea of using mobile
      phones to receive this kind of intervention and indicated that video-tailored
      messages should be shorter than 5 minutes. Video-delivery of content is very rich
      in information, which increases the challenge to appropriately tailor content to
      participant characteristics; focus-group outcomes indicated a large diversity in
      participant preferences. 52.4% of survey participants indicated that the videos
      should be convincing and motivating. CONCLUSIONS: These results provide valuable
      information to develop an innovative video-tailored physical activity
      intervention. The results support the feasibility of such intervention, both in
      terms of users being ready to participate in it, as well as from a point of view
      whereby current internet infrastructure is able to cope with the demands of
      downloading videos. Though promising, a number of specific challenges in the
      development of these interventions were identified (e.g. the videos need to be
      short, made professionally, and tailor to a larger number of variables) and will
      need to be overcome in the development and evaluation of this new type of
      physical activity intervention.

PMID- 21718547
TI  - A qualitative exploration of Malaysian cancer patients' perspectives on cancer
      and its treatment.
AB  - BACKGROUND: Cancer patients' knowledge about cancer and experiences with its
      treatment play an important role in long-term adherence in their disease
      management. This study aimed to explore cancer patients' knowledge about cancer,
      their perceptions of conventional therapies and the factors that contribute to
      medication adherence in the Malaysian population. METHODS: A qualitative research
      approach was adopted to gain a better understanding of the current perceptions
      and knowledge held by cancer patients. Twenty patients were interviewed using a
      semi-structured interview guide. A saturation point was reached after the 18th
      interview, and no new information emerged with the subsequent 2 interviews. All
      interviews were transcribed verbatim and analysed by means of a standard content
      analysis framework. RESULTS: The majority of patients related the cause of their
      cancer to be God's will. Participants perceived conventional therapies as
      effective due to their scientific methods of preparations. A fear of side effects
      was main reasons given for delay in seeking treatment; however, perceptions were
      reported to change after receiving treatment when effective management to reduce
      the risk of side effects had been experienced. CONCLUSIONS: This study provides
      basic information about cancer patients' perceptions towards cancer and its
      treatment. These findings can help in the design of educational programs to
      enhance awareness and acceptances of cancer screening. Priorities for future
      research should focus on patients who refused the conventional therapies at any
      stage.

PMID- 21718548
TI  - Transcriptional profiling of Medicago truncatula under salt stress identified a
      novel CBF transcription factor MtCBF4 that plays an important role in abiotic
      stress responses.
AB  - BACKGROUND: Salt stress hinders the growth of plants and reduces crop production
      worldwide. However, different plant species might possess different adaptive
      mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of
      transcriptional dynamics in the roots of Medicago truncatula seedlings under salt
      stress and selected a transcription factor gene, MtCBF4, for experimental
      validation. RESULTS: A microarray experiment was conducted using root samples
      collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11
      statistically significant expression profiles revealed different behaviors
      between primary and secondary metabolism pathways in response to external stress.
      Secondary metabolism that helps to maintain osmotic balance was induced. One of
      the highly induced transcription factor genes was successfully cloned, and was
      named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the
      AP2-EREBP transcription factor family, is a novel member of the CBF transcription
      factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein.
      Expression of MtCBF4 in M. truncatula was induced by most of the abiotic
      stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk
      between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4
      enhanced tolerance to drought and salt stress, and activated expression of
      downstream genes that contain DRE elements. Over-expression of MtCBF4 in M.
      truncatula also enhanced salt tolerance and induced expression level of
      corresponding downstream genes. CONCLUSION: Comprehensive transcriptomic analysis
      revealed complex mechanisms exist in plants in response to salt stress. The novel
      transcription factor gene MtCBF4 identified here played an important role in
      response to abiotic stresses, indicating that it might be a good candidate gene
      for genetic improvement to produce stress-tolerant plants.

PMID- 21718549
TI  - Detection and characterization of spontaneous internal deletion mutants of Beet
      Necrotic yellow vein virus RNA3 from systemic host Nicotiana benthamiana.
AB  - BACKGROUND: Beet Necrotic Yellow Vein virus (BNYVV) is a member of the genus
      Benyvirus causing a worldwide sugar beet disease rhizomania. BNYVV contains four
      or five plus-sense single stranded RNAs. In altered selective conditions,
      multipartite RNA viruses of plant are prone to undergoing internal deletions,
      thus turning into Defective RNAs (D RNAs). Although several D RNAs have been
      reported in BNYVV infection, the spontaneous internal deletion mutants
      responsible for severe symptom in systemic host Nicotiana benthamiana (N.
      benthamiana) are not described so far. RESULTS: Systemic host N. benthamiana was
      inoculated by Chinese BNYVV isolates. RT-PCR and Northern blot showed that the D
      RNAs forms of BNYVV RNA3 were present in the systemic infection of the N.
      benthamiana. Three distinct D-RNA3s, named as D-RNA 3alpha, D-RNA 3beta and D-RNA
      3gamma, were made into infectious clones. When inoculated on the N. benthamiana,
      the in vitro transcripts of D forms exhibited more stable than that of wild-type
      RNA3 in systemic movement. Among the detected mutant, the p25 protein frame-shift
      mutant (D-RNA3alpha) induced obvious necrotic lesions on Tetragonia.expansa (T.
      expansa) and pronounced systemic symptom on the N. benthamiana. The D-RNA3alpha
      was further mutated artificially to pre-terminate the downstream N protein,
      leading to the abolishment of the pathogenicity, indicating the N protein was
      responsible for the necrotic symptom. CONCLUSION: Our studies demonstrated the
      internal deletion mutants of BNYVV-RNA3 were spontaneously generated in the
      systemic infection on N. benthamiana. The internal deletions didn't affect the
      efficient replication of D-RNA3s, instead by improving the stability and
      pathogenicity of RNA3 in the systemic host N. benthamiana. Besides, our results
      also suggested the downstream N protein of RNA3, but not the upstream p25
      protein, may play an important role in the systemic infection on N. benthamiana.

PMID- 21718550
TI  - Taxon ordering in phylogenetic trees by means of evolutionary algorithms.
AB  - BACKGROUND: In in a typical "left-to-right" phylogenetic tree, the vertical order
      of taxa is meaningless, as only the branch path between them reflects their
      degree of similarity. To make unresolved trees more informative, here we propose
      an innovative Evolutionary Algorithm (EA) method to search the best graphical
      representation of unresolved trees, in order to give a biological meaning to the
      vertical order of taxa. METHODS: Starting from a West Nile virus phylogenetic
      tree, in a (1 + 1)-EA we evolved it by randomly rotating the internal nodes and
      selecting the tree with better fitness every generation. The fitness is a sum of
      genetic distances between the considered taxon and the r (radius) next taxa.
      After having set the radius to the best performance, we evolved the trees with
      (lambda + MU)-EAs to study the influence of population on the algorithm. RESULTS:
      The (1 + 1)-EA consistently outperformed a random search, and better results were
      obtained setting the radius to 8. The (lambda + MU)-EAs performed as well as the
      (1 + 1), except the larger population (1000 + 1000). CONCLUSIONS: The trees after
      the evolution showed an improvement both of the fitness (based on a genetic
      distance matrix, then close taxa are actually genetically close), and of the
      biological interpretation. Samples collected in the same state or year moved
      close each other, making the tree easier to interpret. Biological relationships
      between samples are also easier to observe.

PMID- 21718551
TI  - RsaI repetitive DNA in Buffalo Bubalus bubalis representing retrotransposons,
      conserved in bovids, are part of the functional genes.
AB  - BACKGROUND: Repetitive sequences are the major components of the eukaryotic
      genomes. Association of these repeats with transcribing sequences and their
      regulation in buffalo Bubalus bubalis has remained largely unresolved. RESULTS:
      We cloned and sequenced RsaI repeat fragments pDp1, pDp2, pDp3, pDp4 of 1331,
      651, 603 and 339 base pairs, respectively from the buffalo, Bubalus bubalis. Upon
      characterization, these fragments were found to represent retrotransposons and
      part of some functional genes. The resultant clones showed cross hybridization
      only with buffalo, cattle, goat and sheep genomic DNA. Real Time PCR, detected ~2
      * 10(4) copies of pDp1, ~ 3000 copies of pDp2 and pDp3 and ~ 1000 of pDp4 in
      buffalo, cattle, goat and sheep genomes, respectively. RsaI repeats are
      transcriptionally active in somatic tissues and spermatozoa. Accordingly, pDp1
      showed maximum expression in lung, pDp2 and pDp3 both in Kidney, and pDp4 in
      ovary. Fluorescence in situ hybridization showed repeats to be distributed all
      across the chromosomes. CONCLUSIONS: The data suggest that RsaI repeats have been
      incorporated into the exonic regions of various transcribing genes, possibly
      contributing towards the architecture and evolution of the buffalo and related
      genomes. Prospects of our present work in the context of comparative and
      functional genomics are highlighted.

PMID- 21718552
TI  - Sickle cell disease.
AB  - INTRODUCTION: Sickle cell disease causes chronic haemolytic anaemia, dactylitis,
      and painful acute crises. It also increases the risk of stroke, organ damage,
      bacterial infections, and complications of blood transfusion. In sub-Saharan
      Africa, up to a third of adults are carriers of the defective sickle cell gene,
      and 1% to 2% of babies are born with the disease. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: what are the effects of pharmaceutical and non-pharmaceutical
      interventions to prevent sickle cell crisis and other acute complications in
      people with sickle cell disease? What are the effects of pharmaceutical and non
      pharmaceutical interventions to treat pain in people with sickle cell crisis? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to March 2010 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 38 systematic reviews, RCTs, or observational studies that met
      our inclusion criteria. We performed a GRADE evaluation of the quality of
      evidence for interventions. CONCLUSIONS: In this systematic review we present
      information relating to the effectiveness and safety of the following
      interventions: acupuncture, antibiotic prophylaxis in children <5 years of age,
      antibiotic prophylaxis in children >5 years of age, aspirin, avoidance of cold
      environment, blood transfusion, codeine, corticosteroid (with narcotic
      analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting
      physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral
      after initial intravenous bolus, repeated intravenous doses), oxygen,
      paracetamol, patient-controlled analgesia, pneumococcal vaccines, and
      rehydration.

PMID- 21718553
TI  - Recurrent miscarriage.
AB  - INTRODUCTION: Recurrent miscarriage is the spontaneous loss of three or more
      consecutive pregnancies with the same biological father in the first trimester,
      and affects 1% to 2% of women, half of whom have no identifiable cause. Overall,
      75% of affected women will have a successful subsequent pregnancy, but this rate
      falls for older mothers and with increasing number of miscarriages.
      Antiphospholipid syndrome, with anticardiolipin or lupus anticoagulant
      antibodies, is present in 15% of women with recurrent first and second trimester
      miscarriage. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
      answer the following clinical questions: What are the effects of treatments for
      unexplained recurrent miscarriage? What are the effects of treatments for
      recurrent miscarriage caused by antiphospholipid syndrome? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to January 2010
      (Clinical Evidence reviews are updated periodically, please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      14 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: aspirin
      (low dose), bed-rest, corticosteroids, early scanning in subsequent pregnancies,
      heparin plus low-dose aspirin, human chorionic gonadotrophin, intravenous
      immunoglobulin treatment, lifestyle adaptation, oestrogen, paternal white cell
      immunisation, progesterone, trophoblastic membrane infusion, and vitamin
      supplementation.

PMID- 21718554
TI  - Pre-eclampsia, eclampsia, and hypertension.
AB  - INTRODUCTION: Pre-eclampsia (raised blood pressure and proteinuria) complicates
      2% to 8% of pregnancies, and raises morbidity and mortality in the mother and
      child. Pre-eclampsia is more common in women with multiple pregnancy and in those
      who have conditions associated with microvascular disease. METHODS AND OUTCOMES:
      We conducted a systematic review and aimed to answer the following clinical
      questions: what are the effects of preventive interventions in women at risk of
      pre-eclampsia? What are the effects of interventions in women who develop mild to
      moderate hypertension during pregnancy? What are the effects of interventions in
      women who develop severe pre-eclampsia or very high blood pressure during
      pregnancy? What is the best choice of anticonvulsant for women with eclampsia? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to February 2010 (Clinical Evidence reviews are updated periodically, please
      check our website for the most up-to-date version of this review). We included
      harms alerts from relevant organisations such as the US Food and Drug
      Administration (FDA) and the UK Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: We found 69 systematic reviews, RCTs, or observational
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review we
      present information relating to the effectiveness and safety of the following
      interventions: anticonvulsants, antihypertensive drugs, antioxidants,
      antiplatelet drugs, atenolol, bed rest, hospital admission, or day care, calcium
      supplementation, choice of analgesia during labour, early delivery
      (interventionist care), evening primrose oil, fish oil, glyceryl trinitrate,
      magnesium supplementation, plasma volume expansion, and salt restriction.

PMID- 21718555
TI  - Diarrhoea in adults (acute).
AB  - INTRODUCTION: An estimated 4.6 billion cases of diarrhoea occurred worldwide in
      2004, resulting in 2.2 million deaths. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of treatments for acute diarrhoea in adults living in resource-rich
      countries? What are the effects of treatments for acute mild-to-moderate
      diarrhoea in adults from resource-rich countries travelling to resource-poor
      countries? What are the effects of treatments for acute mild-to-moderate
      diarrhoea in adults living in resource-poor countries? What are the effects of
      treatments for acute severe diarrhoea in adults living in resource-poor
      countries? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to January 2010 (Clinical Evidence reviews are updated
      periodically, please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 72 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: antibiotics, antimotility agents, antisecretory
      agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube
      rehydration, oral rehydration solutions (amino acid oral rehydration solution,
      bicarbonate oral rehydration solution, reduced osmolarity oral rehydration
      solution, rice-based oral rehydration solution, standard oral rehydration
      solution), vitamin A supplementation, and zinc supplementation.

PMID- 21718556
TI  - Dysmenorrhoea.
AB  - INTRODUCTION: Dysmenorrhoea may begin soon after the menarche, after which it
      often improves with age, or it may originate later in life after the onset of an
      underlying causative condition. Dysmenorrhoea is common, and in up to 20% of
      women it may be severe enough to interfere with daily activities. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical question: What are the effects of treatments for primary dysmenorrhoea?
      We searched: Medline, Embase, The Cochrane Library, and other important databases
      up to January 2010 (Clinical Evidence reviews are updated periodically, please
      check our website for the most up-to-date version of this review). We included
      harms alerts from relevant organisations such as the US Food and Drug
      Administration (FDA) and the UK Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: We found 35 systematic reviews, RCTs, or observational
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review we
      present information relating to the effectiveness and safety of the following
      interventions: acupressure, acupuncture, aspirin, behavioural interventions,
      contraceptives (combined oral), fish oil, herbal remedies, magnets, non-steroidal
      anti-inflammatory drugs, paracetamol, progestogens (intrauterine), spinal
      manipulation, surgical interruption of pelvic nerve pathways, thiamine, toki
      shakuyaku-san, topical heat, transcutaneous electrical nerve stimulation (TENS),
      vitamin B12, and vitamin E.

PMID- 21718557
TI  - ADHD in children and adolescents.
AB  - INTRODUCTION: Prevalence estimates of attention deficit hyperactivity disorder
      (ADHD) vary according to the diagnostic criteria used and the population sampled.
      DSM-IV prevalence estimates among school children in the US are 3% to 5%, but
      other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the
      diagnosis of ADHD, which remains a clinical diagnosis. Other conditions
      frequently co-exist with ADHD. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical questions: What are the effects
      of pharmacological treatments for ADHD in children and adolescents? What are the
      effects of psychological treatments for ADHD in children and adolescents? What
      are the effects of combination treatments for ADHD in children and adolescents?
      We searched: Medline, Embase, The Cochrane Library, and other important databases
      up to August 2009 (Clinical Evidence reviews are updated periodically, please
      check our website for the most up-to-date version of this review). We included
      harms alerts from relevant organisations such as the US Food and Drug
      Administration (FDA) and the UK Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: We found 70 systematic reviews, RCTs, or observational
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review we
      present information relating to the effectiveness and safety of the following
      interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate,
      homeopathy, methylphenidate, modafinil, omega-3 polyunsaturated fatty acids, and
      psychological/behavioural treatment (either alone or in combination with a drug
      treatment).

PMID- 21718558
TI  - Primary prevention of CVD: diet.
AB  - INTRODUCTION: Diet is important in the cause of many chronic diseases. Individual
      change in dietary behaviour has the potential to decrease the burden of chronic
      disease, particularly cardiovascular disease (CVD). METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      question: What are the effects of dietary advice in generally healthy adults
      without existing CVD or increased CVD risk factors to improve cardiovascular
      outcomes (mortality, cardiovascular events, and cardiovascular risk factors)? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to April 2010 (Clinical Evidence reviews are updated periodically, please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 14 systematic reviews or RCTs that met our inclusion criteria.
      We performed a GRADE evaluation of the quality of evidence for interventions.
      CONCLUSIONS: In this systematic review we present information relating to the
      effectiveness and safety of the following interventions: advice to increase fibre
      intake alone, advice to increase fruit and vegetable intake alone, advice to
      reduce and/or modify fat intake alone, and advice to reduce sodium intake alone.

PMID- 21718559
TI  - Atrial fibrillation (acute onset).
AB  - INTRODUCTION: Acute atrial fibrillation is rapid, irregular, and chaotic atrial
      activity of less than 48 hours' duration. Risk factors for acute atrial
      fibrillation include increasing age, cardiovascular disease, alcohol, diabetes,
      and lung disease. Acute atrial fibrillation increases the risk of stroke and
      heart failure. The condition resolves spontaneously within 24 to 48 hours in over
      50% of people; however, many people will require interventions to control heart
      rate or restore sinus rhythm. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical questions: What are the effects
      of interventions to prevent embolism, for conversion to sinus rhythm, and to
      control heart rate in people with recent-onset atrial fibrillation (within 7
      days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to April 2010 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 30
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions:
      amiodarone, antithrombotic treatment before cardioversion, digoxin, diltiazem,
      direct current cardioversion, flecainide, propafenone, quinidine, sotalol,
      timolol, and verapamil.

PMID- 21718560
TI  - Breast cancer (non-metastatic).
AB  - INTRODUCTION: Breast cancer affects at least 1 in 10 women in the UK, but most
      present with primary operable disease, which has an 80% 5-year survival rate
      overall. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
      answer the following clinical questions: What are the effects of interventions
      after breast-conserving surgery for ductal carcinoma in situ? What are the
      effects of treatments for primary operable breast cancer? What are the effects of
      interventions in locally advanced breast cancer (stage 3B)? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to April 2009
      (Clinical Evidence reviews are updated periodically, please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      83 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: adding
      chemotherapy (cyclophosphamide/methotrexate/fluorouracil and/or anthracycline
      and/or taxane-based regimens), or hormonal treatment to radiotherapy; adjuvant
      treatments (aromatase inhibitors, adjuvant anthracycline regimens, tamoxifen);
      axillary clearance; axillary dissection plus sentinel node dissection; axillary
      radiotherapy; axillary sampling; combined chemotherapy plus tamoxifen;
      chemotherapy plus monoclonal antibody (trastuzumab); extensive surgery; high-dose
      chemotherapy; hormonal treatment; less extensive mastectomy; less than whole
      breast radiotherapy plus breast-conserving surgery; multimodal treatment; ovarian
      ablation; primary chemotherapy; prolonged adjuvant combination chemotherapy;
      radiotherapy (after breast-conserving surgery, after mastectomy, plus tamoxifen
      after breast-conserving surgery, to the internal mammary chain, and to the
      ipsilateral supraclavicular fossa, and total nodal radiotherapy); sentinel node
      biopsy; and standard chemotherapy regimens.

PMID- 21718561
TI  - Cataract.
AB  - INTRODUCTION: Cataract accounts for over 47% of blindness worldwide, causing
      blindness in about 17.3 million people in 1990. Surgery for cataract in people
      with glaucoma may affect glaucoma control. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of surgery for age-related cataract without other ocular comorbidity?
      What are the effects of treatment for age-related cataract in people with
      glaucoma? What are the effects of surgical treatments for age-related cataract in
      people with diabetic retinopathy? What are the effects of surgical treatments for
      age-related cataract in people with chronic uveitis? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to May 2010
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      20 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: for
      people with cataract without other ocular co-morbidity: cataract surgery alone,
      cataract surgery with non-concomitant glaucoma surgery, concomitant cataract and
      glaucoma surgery, intracapsular extraction, manual (large or small) incision
      extracapsular extraction, and phaco extracapsular extraction; for people with
      cataract with co-morbid diabetic retinopathy: cataract surgery alone, and adding
      diabetic retinopathy treatment to cataract surgery; for people with cataract and
      co-morbid chronic uveitis: cataract surgery, and medical control of uveitis at
      the time of cataract surgery.

PMID- 21718562
TI  - Altitude sickness.
AB  - INTRODUCTION: Up to half of people who ascend to heights above 2500 m may develop
      acute mountain sickness, pulmonary oedema, or cerebral oedema, with the risk
      being greater at higher altitudes, and with faster rates of ascent. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of interventions to prevent, and to
      treat, acute mountain sickness? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to October 2009 (Clinical Evidence
      reviews are updated periodically, please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 17
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions:
      acetazolamide, descent versus resting, dexamethasone, gingko biloba, and slow
      ascent.

PMID- 21718563
TI  - Bacterial conjunctivitis.
AB  - INTRODUCTION: Most cases of conjunctivitis in adults are probably due to viral
      infection, but children are more likely to develop bacterial conjunctivitis than
      they are viral forms. The main bacterial pathogens are Haemophilus influenzae and
      Streptococcus pneumoniae in adults and children, and Moraxella catarrhalis in
      children. Contact lens wearers may be more likely to develop gram-negative
      infections. Bacterial keratitis occurs in up to 30 per 100,000 contact lens
      wearers. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
      answer the following clinical questions: What are the effects of empirical
      treatment in adults and children with suspected bacterial conjunctivitis? What
      are the effects of treatment in adults and children with bacteriologically
      confirmed bacterial conjunctivitis? What are the effects of treatment in adults
      and children with clinically confirmed gonococcal conjunctivitis? We searched:
      Medline, Embase, The Cochrane Library, and other important databases up to July
      2009 (Clinical Evidence reviews are updated periodically; please check our
      website for the most up-to-date version of this review). We included harms alerts
      from relevant organisations such as the US Food and Drug Administration (FDA) and
      the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We
      found 40 systematic reviews, RCTs, or observational studies that met our
      inclusion criteria. We performed a GRADE evaluation of the quality of evidence
      for interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: ocular
      decongestants; oral antibiotics; parenteral antibiotics; saline; topical
      antibiotics; and warm compresses.

PMID- 21718564
TI  - Anal fissure (chronic).
AB  - INTRODUCTION: Anal fissures are a common cause of anal pain during, and for 1 to
      2 hours after, defecation. The cause is not fully understood, but low intake of
      dietary fibre may be a risk factor. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of non-surgical treatments for chronic anal fissure? What are the
      effects of surgical treatments for chronic anal fissure? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to August 2009
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      28 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: anal
      advancement flap, anal stretch/dilation, botulinum A toxin-haemagglutinin complex
      alone or with nitrates, calcium channel blockers, internal anal sphincterotomy,
      and nitric oxide donors.

PMID- 21718565
TI  - Carpal tunnel syndrome.
AB  - INTRODUCTION: Carpal tunnel syndrome is a neuropathy caused by compression of the
      median nerve within the carpal tunnel. However, the severity of symptoms and
      signs does not often correlate well with the extent of nerve damage. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of drug treatments, non-drug treatments,
      surgical treatments, and postoperative treatments for carpal tunnel syndrome? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to March 2009 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 53 systematic reviews, RCTs, or observational studies that met
      our inclusion criteria. We performed a GRADE evaluation of the quality of
      evidence for interventions. CONCLUSIONS: In this systematic review we present
      information relating to the effectiveness and safety of the following
      interventions: acupuncture, carpal tunnel release surgery (open and endoscopic),
      diuretics, internal neurolysis, local and systemic corticosteroids, massage
      therapy, nerve and tendon gliding exercises, non-steroidal anti-inflammatory
      drugs (NSAIDs), pyridoxine, therapeutic ultrasound, and wrist splints.

PMID- 21718566
TI  - Ankle sprain.
AB  - INTRODUCTION: Injury of the lateral ligament complex of the ankle joint occurs in
      about one in 10,000 people a day, accounting for a quarter of all sports
      injuries. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
      answer the following clinical question: What are the effects of treatment
      strategies for acute ankle ligament ruptures? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to November 2009 (Clinical
      Evidence reviews are updated periodically, please check our website for the most
      up-to-date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 38
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: cold
      treatment, diathermy, functional treatment, homeopathic ointment, immobilisation,
      physiotherapy, surgery, and ultrasound.

PMID- 21718567
TI  - Basal cell carcinoma.
AB  - INTRODUCTION: Basal cell carcinoma (BCC) is the most common form of skin cancer,
      predominantly affecting the head and neck, and can be diagnosed clinically in
      most cases. Metastasis of BCC is rare, but localised tissue invasion and
      destruction can lead to morbidity. Incidence of BCC increases markedly after the
      age of 40 years, but incidence in younger people is rising, possibly as a result
      of increased sun exposure. METHODS AND OUTCOMES: We conducted a systematic review
      and aimed to answer the following clinical questions: What are the effects of
      interventions on treatment response/recurrence (within 1 year of therapy) in
      people with basal cell carcinoma? What are the effects of interventions on long
      term recurrence (a minimum of 2 years after treatment) in people with basal cell
      carcinoma? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to December 2009 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 16 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: cryotherapy/cryosurgery, curettage and
      cautery/electrodesiccation, fluorouracil, imiquimod 5% cream, photodynamic
      therapy, and surgery (conventional or Mohs' micrographic surgery).

PMID- 21718568
TI  - Chlamydia (uncomplicated, genital).
AB  - INTRODUCTION: Genital chlamydia is the most commonly reported bacterial sexually
      transmitted infection (STI) in developed countries. In women, infection occurs
      most commonly between the ages of 16 and 19 years. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of antibiotic treatment for men and non-pregnant
      women with uncomplicated genital chlamydial infection?What are the effects of
      antibiotic treatment for pregnant women with uncomplicated genital chlamydial
      infection? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to September 2009 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 24 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: amoxicillin, ampicillin, azithromycin,
      ciprofloxacin, clarithromycin, clindamycin, doxycycline, erythromycin,
      lymecycline, minocycline, ofloxacin, pivampicillin, rifampicin, roxithromycin,
      sparfloxacin, tetracycline, and trovafloxacin.

PMID- 21718569
TI  - Colorectal cancer treatment.
AB  - INTRODUCTION: Colorectal cancer is the third most common malignancy in the
      developed countries, and about a quarter of people present with intestinal
      obstruction or perforation. Risk factors for colorectal cancer are mainly dietary
      and genetic. Overall 5-year survival is about 50%, with half of people having
      surgery experiencing recurrence of the disease. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      question: What are the effects of treatments for colorectal cancer? We searched:
      Medline, Embase, The Cochrane Library, and other important databases up to August
      2008 (Clinical Evidence reviews are updated periodically, please check our
      website for the most up-to-date version of this review). We included harms alerts
      from relevant organisations such as the US Food and Drug Administration (FDA) and
      the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We
      found 57 systematic reviews, RCTs, or observational studies that met our
      inclusion criteria. We performed a GRADE evaluation of the quality of evidence
      for interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: adjuvant
      systemic chemotherapy, preoperative radiotherapy, and routine intensive follow
      up.

PMID- 21718570
TI  - Constipation in children.
AB  - INTRODUCTION: Prevalence of childhood constipation has been estimated at 0.7% to
      29.6% in the general population worldwide; most children have no obvious
      aetiological factors. One third of children with chronic constipation continue to
      have problems beyond puberty. Half of children with chronic faecal impaction and
      faecal incontinence have experienced an episode of painful defecation, and many
      children with chronic constipation exhibit withholding behaviour. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of treatments for children with chronic
      constipation? What are the effects of treatments for clearing the bowel in
      children with faecal impaction? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to August 2009 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 14
      systematic reviews and RCTs that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: anal dilatation, behavioural treatments
      (biofeedback, diaries, or toilet training), bulk-forming laxatives, enemas,
      faecal softeners, fibre, macrogols, oral fluids, osmotic laxatives, prebiotics,
      probiotics, stimulant laxatives, and surgical disimpaction.

PMID- 21718571
TI  - Peripheral arterial disease.
AB  - INTRODUCTION: Up to 20% of adults aged over 55 years have detectable peripheral
      arterial disease of the legs, but this may cause symptoms of intermittent
      claudication in only a small proportion of affected people. The main risk factors
      are smoking and diabetes mellitus, but other risk factors for cardiovascular
      disease are also associated with peripheral arterial disease. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical question: What are the effects of treatments for people with chronic
      peripheral arterial disease? We searched: Medline, Embase, The Cochrane Library,
      and other important databases up to March 2009. (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 59 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: antiplatelet agents; bypass surgery;
      cilostazol; exercise; pentoxifylline; percutaneous transluminal angioplasty
      (PTA); prostaglandins; smoking cessation; and statins.

PMID- 21718572
TI  - Constipation in people prescribed opioids.
AB  - INTRODUCTION: Constipation is reported in 52% of people with advanced malignancy.
      This figure rises to 87% in people who are terminally ill and taking opioids.
      Constipation may be the most common adverse effect of opioids. There is no reason
      to believe that people with chronic non-malignant disease who take opioids will
      be any less troubled by this adverse effect. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of: oral laxatives, rectally applied medications, and opioid
      antagonists for constipation in people prescribed opioids? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to August 2009
      (Clinical Evidence reviews are updated periodically, please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      23 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: arachis
      oil enemas, bisacodyl, co-danthrusate/co-danthramer, docusate, glycerol
      suppositories, ispaghula husk, lactulose, liquid paraffin, macrogols plus
      electrolyte solutions, magnesium salts, methylcellulose, opioid antagonists,
      phosphate enemas, senna, sodium citrate micro-enema, and sodium picosulfate.

PMID- 21718573
TI  - Alcohol misuse.
AB  - INTRODUCTION: Alcohol use is a leading cause of mortality and morbidity
      internationally, and is ranked by the World Health Organization (WHO) as one of
      the top five risk factors for disease burden. Without treatment, approximately
      16% of hazardous or harmful alcohol users will progress to more dependent
      patterns of alcohol consumption. This review covers interventions in hazardous or
      harmful, but not dependent, alcohol users. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of interventions in hazardous or harmful drinkers in the primary-care
      setting? What are the effects of interventions in hazardous or harmful drinkers
      in the emergency-department setting? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to February 2009 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 18
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions in
      primary care and in emergency departments: brief intervention (single- or
      multiple-session); universal screening plus brief interventions; and targeted
      screening plus brief interventions.

PMID- 21718574
TI  - Tonsillitis.
AB  - INTRODUCTION: The definition of severe recurrent throat infections is arbitrary,
      but recent criteria have defined severe tonsillitis as: five or more episodes of
      true tonsillitis a year; symptoms for at least 1 year; and episodes that are
      disabling and prevent normal functioning. Diagnosis of acute tonsillitis is
      clinical, and it can be difficult to distinguish viral from bacterial infections.
      Rapid antigen testing has a very low sensitivity in the diagnosis of bacterial
      tonsillitis, but more accurate tests take longer to deliver results. Bacteria are
      cultured from few people with tonsillitis. Other causes include infectious
      mononucleosis from Epstein-Barr virus infection, cytomegalovirus, toxoplasmosis,
      HIV, hepatitis A, and rubella. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical question: What are the effects
      of tonsillectomy in children and adults with acute recurrent or chronic throat
      infections? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to March 2009 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 10 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: cold-steel tonsillectomy and diathermy
      tonsillectomy.

PMID- 21718575
TI  - Helicobacter pylori infection.
AB  - INTRODUCTION: The principal effect of Helicobacter pylori infection is lifelong
      chronic gastritis, affecting up to 20% of younger adults but 50% to 80% of adults
      born in resource-rich countries before 1950. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of H pylori eradication treatment in people with a confirmed duodenal
      ulcer, a confirmed gastric ulcer, confirmed gastro-oesophageal reflux disease
      (GORD), confirmed non-ulcer dyspepsia, uninvestigated dyspepsia, localised B cell
      lymphoma of the stomach, and non-steroidal anti-inflammatory drug (NSAID)-related
      peptic ulcers? What are the effects of H pylori eradication treatment for
      preventing NSAID-related peptic ulcers in people with or without previous ulcers
      or dyspepsia? What are the effects of H pylori eradication treatment on the risk
      of developing gastric cancer? Do H pylori eradication treatments differ in their
      effects? We searched: Medline, Embase, The Cochrane Library, and other important
      databases up to September 2007 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 58 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: effects of H pylori eradication in different
      populations; relative effects of triple regimens, quadruple regimens, and
      sequential regimens.

PMID- 21718576
TI  - Burns (minor thermal).
AB  - INTRODUCTION: Superficial burns that affect the epidermis and upper dermis only
      are characterised by redness of the skin that blanches on pressure, pain, and
      hypersensitivity. The skin blisters within hours and usually heals with minimal
      scarring within 2 to 3 weeks if no infection is present. Most minor burns occur
      in the home, with less than 5% requiring hospital treatment. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical question: What are the effects of treatments for minor thermal burns? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to October 2008 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found eight systematic reviews, RCTs, or observational studies that
      met our inclusion criteria. We performed a GRADE evaluation of the quality of
      evidence for interventions. CONCLUSIONS: In this systematic review, we present
      information relating to the effectiveness and safety of the following
      interventions: alginate dressing; antibiotics; chlorhexidine-impregnated paraffin
      gauze dressing; foam dressing; hydrocolloid dressing; hydrogel dressing; paraffin
      gauze dressing; polyurethane film; silicone-coated nylon dressing; and silver
      sulfadiazine cream.

PMID- 21718577
TI  - Asthma in adults.
AB  - INTRODUCTION: About 10% of adults have suffered an attack of asthma, and up to 5%
      of these have severe disease that responds poorly to treatment. Patients with
      severe disease have an increased risk of death, but patients with mild-to
      moderate disease are also at risk of exacerbations. Most guidelines about the
      management of asthma follow stepwise protocols. This review does not endorse or
      follow any particular protocol, but presents the evidence about specific
      interventions. METHODS AND OUTCOMES: We conducted a systematic review and aimed
      to answer the following clinical questions: What are the effects of treatments
      for chronic asthma? What are the effects of treatments for acute asthma? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to June 2008 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 99 systematic reviews, RCTs, or observational studies that met
      our inclusion criteria. We performed a GRADE evaluation of the quality of
      evidence for interventions. CONCLUSIONS: In this systematic review, we present
      information relating to the effectiveness and safety of the following
      interventions. For acute asthma: beta(2) agonists (plus ipratropium bromide,
      pressured metered-dose inhalers, short-acting continuous nebulised, short-acting
      intermittent nebulised, and short-acting intravenous); corticosteroids (inhaled);
      corticosteroids (single oral, combined inhaled, and short courses); education
      about acute asthma; generalist care; helium-oxygen mixture (heliox); magnesium
      sulphate (intravenous and adding isotonic nebulised magnesium to inhaled beta(2)
      agonists); mechanical ventilation; oxygen supplementation (controlled 28% oxygen
      and controlled 100% oxygen); and specialist care. For chronic asthma: beta(2)
      agonists (adding long-acting inhaled beta(2) agonists when asthma is poorly
      controlled by inhaled corticosteroids, or short-acting inhaled beta(2) agonists
      as needed for symptom relief); inhaled corticosteroids (low dose and increasing
      dose); leukotriene antagonists (with or without inhaled corticosteroids); and
      theophylline (when poorly controlled by inhaled corticosteroids).

PMID- 21718578
TI  - Irritable bowel syndrome.
AB  - INTRODUCTION: The prevalence of irritable bowel syndrome (IBS) varies depending
      on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is
      associated with abnormal gastrointestinal motor function and enhanced visceral
      perception, as well as psychosocial and genetic factors. People with IBS often
      have other bodily and psychiatric symptoms, and have an increased likelihood of
      having unnecessary surgery compared with people without IBS. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical question: What are the effects of treatments in people with IBS? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to July 2009 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 18 systematic reviews, RCTs, or observational studies that met
      our inclusion criteria. We performed a GRADE evaluation of the quality of
      evidence for interventions. CONCLUSIONS: In this systematic review we present
      information relating to the effectiveness and safety of the following
      interventions: 5HT(3) receptor antagonists (alosetron and ramosetron); 5HT(4)
      receptor agonists (tegaserod); antidepressants (tricyclic antidepressants and
      selective serotonin reuptake inhibitors [SSRIs]); antispasmodics (including
      peppermint oil); cognitive behavioural therapy (CBT); hypnotherapy; soluble and
      insoluble fibre supplementation; and loperamide.

PMID- 21718579
TI  - Candidiasis (vulvovaginal).
AB  - INTRODUCTION: Vulvovaginal candidiasis is estimated to be the second most common
      cause of vaginitis after bacterial vaginosis. Candida albicans accounts for 85%
      to 90% of cases. METHODS AND OUTCOMES: We conducted a systematic review and aimed
      to answer the following clinical questions: What are the effects of drug
      treatments for acute vulvovaginal candidiasis in non-pregnant symptomatic women?
      What are the effects of alternative or complementary treatments for acute
      vulvovaginal candidiasis in non-pregnant symptomatic women? What are the effects
      of treating a male sexual partner to resolve symptoms and prevent recurrence in
      non-pregnant women with symptomatic acute vulvovaginal candidiasis? What are the
      effects of alternative or complementary treatments for symptomatic recurrent
      vulvovaginal candidiasis in non-pregnant women? What are the effects of treating
      a male sexual partner in non-pregnant women with symptomatic recurrent
      vulvovaginal candidiasis? What are the effects of treating asymptomatic non
      pregnant women with a positive swab for candidiasis? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to March 2009
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      61 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions:
      alternative or complementary treatments; douching; drug treatments; garlic;
      intravaginal preparations (boric acid, nystatin, imidazoles, tea tree oil); oral
      fluconazole; oral itraconazole; treating a male sexual partner; and yoghurt
      containing Lactobacillus acidophilus (oral or vaginal).

PMID- 21718580
TI  - Post-traumatic stress disorder.
AB  - INTRODUCTION: Post-traumatic stress disorder (PTSD) may affect 10% of women and
      5% of men at some stage, and symptoms may persist for several years. Risk factors
      include major trauma, lack of social support, peritraumatic dissociation, and
      previous psychiatric history or personality factors. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of interventions to prevent PTSD? What are the
      effects of interventions to treat PTSD? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to March 2009 (Clinical
      Evidence reviews are updated periodically; please check our website for the most
      up-to-date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 46
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: affect
      management; antiepileptic drugs; antihypertensive drugs; benzodiazepines;
      brofaromine; CBT; drama therapy; eye movement desensitisation and reprocessing;
      fluoxetine; group therapy; hydrocortisone; hypnotherapy; inpatient treatment
      programmes; Internet-based psychotherapy; mirtazapine; multiple-session CBT;
      multiple-session collaborative trauma support; multiple-session education;
      nefazodone; olanzapine; paroxetine; phenelzine; psychodynamic psychotherapy;
      risperidone; SSRIs (versus other antidepressants); sertraline; single-session
      group debriefing; single-session individual debriefing; supportive psychotherapy;
      supportive counselling; temazepam; tricyclic antidepressants; and venlafaxine.

PMID- 21718581
TI  - Hepatitis C (chronic).
AB  - INTRODUCTION: About 60% to 85% of people infected with hepatitis C virus will go
      on to develop chronic hepatitis C, which is now believed to affect 3% of the
      world's population. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical questions: What are the effects of
      interventions in treatment-naive people with chronic hepatitis C infection, but
      without liver decompensation? What are the effects of interventions in people
      with chronic hepatitis C infection, but without liver decompensation, who have
      not responded to interferon treatment? What are the effects of interventions in
      people with chronic hepatitis C infection, but without liver decompensation, who
      relapse after interferon treatment? What are the effects of interventions in
      people with chronic hepatitis C infection who also have HIV? We searched:
      Medline, Embase, The Cochrane Library, and other important databases up to April
      2008 (Clinical Evidence reviews are updated periodically; please check our
      website for the most up-to-date version of this review). We included harms alerts
      from relevant organisations such as the FDA and the UK Medicines and Healthcare
      products Regulatory Agency (MHRA). RESULTS: We found 35 systematic reviews, RCTs,
      or observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: interferon monotherapy; interferon alfa plus
      ribavirin; peginterferon monotherapy; and peginterferon plus ribavirin.

PMID- 21718582
TI  - Menopausal symptoms.
AB  - INTRODUCTION: Menopause is a physiological event. In the UK, the median age for
      onset of menopausal symptoms is 45.5 to 47.5 years. Although endocrine changes
      are permanent, menopausal symptoms such as hot flushes, which are experienced by
      about 70% of women, usually resolve with time, although they can persist for
      decades in some women. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical questions: What are the effects of medical
      treatments for menopausal symptoms? What are the effects of non-prescribed
      treatments for menopausal symptoms? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to March 2009 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 68
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: agnus
      castus; antidepressants; black cohosh; clonidine; oestrogens; phyto-oestrogens;
      progestogens; testosterone; and tibolone.

PMID- 21718583
TI  - Heart failure.
AB  - INTRODUCTION: Heart failure occurs in 3% to 4% of adults aged over 65 years,
      usually as a consequence of coronary artery disease or hypertension, and causes
      breathlessness, effort intolerance, fluid retention, and increased mortality. The
      5-year mortality in people with systolic heart failure ranges from 25% to 75%,
      often owing to sudden death following ventricular arrhythmia. Risks of
      cardiovascular events are increased in people with left ventricular systolic
      dysfunction (LVSD) or heart failure. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of non-drug treatments, and of drug and invasive treatments, for
      heart failure? What are the effects of angiotensin-converting enzyme inhibitors
      in people at high risk of heart failure? What are the effects of treatments for
      diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and
      other important databases up to May 2009 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 85 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: aldosterone receptor antagonists; amiodarone;
      angiotensin-converting enzyme inhibitors; angiotensin II receptor blockers;
      anticoagulation; antiplatelet agents; beta-blockers; calcium channel blockers;
      cardiac resynchronisation therapy; digoxin (in people already receiving diuretics
      and angiotensin-converting enzyme inhibitors); exercise; hydralazine plus
      isosorbide dinitrate; implantable cardiac defibrillators; multidisciplinary
      interventions; non-amiodarone antiarrhythmic drugs; and positive inotropes (other
      than digoxin).

PMID- 21718584
TI  - Cluster headache.
AB  - INTRODUCTION: The revised International Headache Society (IHS) criteria for
      cluster headache are: attacks of severe or very severe, strictly unilateral pain,
      which is orbital, supraorbital, or temporal pain, lasting 15 to 180 minutes and
      occurring from once every other day to eight times daily. METHODS AND OUTCOMES:
      We conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of interventions to abort cluster headache? What
      are the effects of interventions to prevent cluster headache? We searched:
      Medline, Embase, The Cochrane Library, and other important databases up to June
      2009 (Clinical Evidence reviews are updated periodically; please check our
      website for the most up-to-date version of this review). We included harms alerts
      from relevant organisations, such as the US Food and Drug Administration (FDA)
      and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS:
      We found 23 systematic reviews, RCTs, or observational studies that met our
      inclusion criteria. We performed a GRADE evaluation of the quality of evidence
      for interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions: baclofen
      (oral); botulinum toxin (intramuscular); capsaicin (intranasal); chlorpromazine;
      civamide (intranasal); clonidine (transdermal); corticosteroids; ergotamine and
      dihydroergotamine (oral or intranasal); gabapentin (oral); greater occipital
      nerve injections (betamethasone plus xylocaine); high-dose and high-flow-rate
      oxygen; hyperbaric oxygen; leuprolide; lidocaine (intranasal); lithium (oral);
      melatonin; methysergide (oral); octreotide (subcutaneous); pizotifen (oral);
      sodium valproate (oral); sumatriptan (oral, subcutaneous, and intranasal);
      topiramate (oral); tricyclic antidepressants (TCAs); verapamil; and zolmitriptan
      (oral and intranasal).

PMID- 21718585
TI  - Letter to the editor: does ketamine exert a fast-acting antidepressant effect via
      inhibition of pro-inflammatory cytokines?

PMID- 21718586
TI  - Statins and myocardial remodelling: cell and molecular pathways.
AB  - The advent of statins has revolutionised the treatment of patients with raised
      plasma cholesterol and increased cardiovascular risk. However, the beneficial
      effects of this class of drugs are far greater than would be expected from
      lowering of cholesterol alone, and they appear to offer cardiovascular protection
      at multiple levels, primarily as a result of their pleiotropic activity. Indeed,
      their favourable effects on the heart seem to be mediated in part through reduced
      prenylation and subsequent inhibition of small GTPases, particularly those of the
      Rho family. Such statin-mediated effects are manifested by reduced onset of heart
      failure and improvements in cardiac dysfunction and remodelling in heart failure
      patients. Experimental studies have shown that statins mediate their effects on
      the two major resident cell types of the heart--cardiomyocytes and cardiac
      fibroblasts--and thus facilitate improvement of adverse remodelling of ischaemic
      or non-ischaemic aetiology. This review examines evidence for the cellular
      effects of statins in the heart, and discusses the underlying molecular
      mechanisms at the level of the cardiomyocyte (hypertrophy, cell death and
      contractile function) and the cardiac fibroblast (differentiation, proliferation,
      migration and extracellular matrix synthesis). The prospects for future therapies
      and ongoing clinical trials are also summarised.

PMID- 21718587
TI  - Public health nutrition interventions can be simple and effective.

PMID- 21718588
TI  - An analysis of the content of food industry pledges on marketing to children.
AB  - OBJECTIVE: To identify pledges made by the food industry to change food marketing
      to children worldwide, examine their content and discuss their potential to
      reduce the harmful effects of food marketing to children. DESIGN: A search for
      pledges and specific commitments made by participating companies and a content
      analysis of their scope and criteria used to define the marketing covered or
      excluded. SETTING: Global. SUBJECTS: Food industry pledges. RESULTS: Between 2005
      and 2009, the food industry developed thirteen pledges on food marketing to
      children, involving fifty-two food companies. Two of the pledges were global, two
      were regional and nine applied to specific countries. Three were specific to the
      soft drinks industry and to the fast-food industry, with the rest being food
      industry wide. Ten of the pledges required companies to publish individual
      commitments; a total of eighty-two such commitments were published, many of which
      extended beyond the minimum standards set in the pledges. All pledges included
      definitions of children and child-targeted media, as well as the communication
      channels and marketing techniques covered, and permitted companies to set
      criteria for foods that are exempted from any restrictions. There were many
      similarities between the pledges and individual commitments; however, there were
      also many differences. CONCLUSIONS: The development of pledges on food marketing
      to children in such a short span of time is impressive. However, limitations and
      inconsistencies in the pledges and commitments suggest that the food industry has
      a long way to go if its pledges are to comprehensively reduce the exposure and
      power of marketing to children.

PMID- 21718589
TI  - Perspectives of breast cancer etiology: synergistic interaction between smoking
      and exogenous hormone use.
AB  - To explore breast cancer etiology, literature was searched using Medline. We
      explored the 1) plausibility of smoking in breast carcinogenesis; 2)
      physiological properties, susceptibility windows, and exposure timing of breast
      cells; 3) role of exogenous hormones in breast carcinogenesis; 4) biological
      mechanism of synergistic interactions between smoking and exogenous hormones in
      breast carcinogenesis; and 5) evidence from epidemiologic studies and the fitted
      secular trend between smoking rate, exogenous hormone use, and breast cancer
      incidence in past decades. We deduced that exogenous hormone use per se is not a
      significant cause and its association with breast cancer is distorted by chronic
      exposure to environmental carcinogens, especially smoking. We hypothesize that
      smoking is one of the causes of breast cancer and that this causality is
      strengthened by synergistic interaction between smoking and exogenous hormone
      use. Physicians should be cautious of prescribing exogenous hormones for those
      with chronic exposure to environmental carcinogens to prevent breast cancer.

PMID- 21718590
TI  - Mouse models of medulloblastoma.
AB  - Medulloblastoma is the most common malignant pediatric brain tumor. Despite its
      prevalence and importance in pediatric neuro-oncology, the genes and pathways
      responsible for its initiation, maintenance, and progression remain poorly
      understood. Genetically engineered mouse models are an essential tool for
      uncovering the molecular and cellular basis of human diseases, including cancer,
      and serve a valuable role as preclinical models for testing targeted therapies.
      In this review, we summarize how such models have been successfully applied to
      the study of medulloblastoma over the past decade and what we might expect in the
      coming years.

PMID- 21718591
TI  - Mouse models of colorectal cancer.
AB  - Colorectal cancer is one of the most common malignancies in the world. Many mouse
      models have been developed to evaluate features of colorectal cancer in humans.
      These can be grouped into genetically-engineered, chemically-induced, and
      inoculated models. However, none recapitulates all of the characteristics of
      human colorectal cancer. It is critical to use a specific mouse model to address
      a particular research question. Here, we review commonly used mouse models for
      human colorectal cancer.

PMID- 21718592
TI  - PARP inhibitors: its role in treatment of cancer.
AB  - PARP is an important protein in DNA repair pathways especially the base excision
      repair (BER). BER is involved in DNA repair of single strand breaks (SSBs). If
      BER is impaired, inhibiting poly(ADP-ribose) polymerase (PARP), SSBs accumulate
      and become double stand breaks (DSBs). The cells with increasing number of DSBs
      become more dependent on other repair pathways, mainly the homologous
      recombination (HR) and the nonhomologous end joining. Patients with defective HR,
      like BRCA-deficient cell lines, are even more susceptible to impairment of the
      BER pathway. Inhibitors of PARP preferentially kill cancer cells in BRCA-mutation
      cancer cell lines over normal cells. Also, PARP inhibitors increase cytotoxicity
      by inhibiting repair in the presence of chemotherapies that induces SSBs. These
      two principles have been tested clinically. Over the last few years, excitement
      over this class of agents has escalated due to reported activity as single agent
      in BRCA1- or BRCA2-associated ovarian or breast cancers, and in combination with
      chemotherapy in triple negative breast cancer. This review covers the current
      results of clinical trials testing those two principles. It also evaluates future
      directions for the field of PARP inhibitor development.

PMID- 21718593
TI  - Tumor shrinkage by cyclopamine tartrate through inhibiting hedgehog signaling.
AB  - The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a
      variety of Hh signaling inhibitors raise great expectation that inhibiting Hh
      signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an
      alkaloid from the Veratrum plant, is a specific natural product inhibitor of the
      Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor
      solubility, acid sensitivity, and weak potency relative to other Hh antagonists
      prevent the clinical development of Cyc as a therapeutic agent. Here, we report
      properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling
      mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10
      mg/mL). The median lethal dose (LD50) of CycT was 62.5 mg/kg body weight compared
      to 43.5 mg/kg for Cyc, and the plasma half-life (T1/2) of CycT was not
      significantly different from that of Cyc. We showed that CycT had a higher
      inhibitory activity for Hh signaling-dependent motor neuron differentiation than
      did Cyc (IC50 = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the
      antitumor effectiveness of these Hh inhibitors using two mouse models of basal
      cell carcinomas (K14cre:Ptch1(neo/neo) and K14cre:SmoM2(YFP)). After topical
      application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice
      had tumor shrinkage and decreased expression of Hh target genes. Taken together,
      we found that CycT is an effective inhibitor of Hh signaling-mediated
      carcinogenesis.

PMID- 21718594
TI  - Treatment results and prognostic factors of patients undergoing postoperative
      radiotherapy for laryngeal squamous cell carcinoma.
AB  - Postoperative radiotherapy (PRT) is widely advocated for patients with squamous
      cell carcinomas of the head and neck that are considered to be at high risk of
      recurrence after surgical resection. The aims of this study were to evaluate the
      treatment outcomes of PRT for patients with laryngeal carcinoma and to identify
      the value of several prognostic factors. We reviewed the records of 256 patients
      treated for laryngeal squamous cell carcinoma between January 1993 and December
      2005. Disease-free survival (DFS) and overall survival (OS) were estimated using
      the Kaplan-Meier method. Log-rank test was employed to identify significant
      prognostic factors for DFS and OS. The Cox proportional hazards model was applied
      to identify covariates significantly associated with the aforementioned
      endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were
      69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were
      80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both
      DFS and OS on univariate analysis were grade, primary site, T stage, N stage,
      overall stage, lymph node metastasis, overall treatment times of radiation, the
      interval between surgery and radiotherapy, and radiotherapy equipment. Favorable
      prognostic factors for both DFS and OS on multivariate analysis were lower
      overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy
      equipment. In conclusion, our data suggest that lower overall stage, no cervical
      lymph node metastasis, and using 60Co as radiotherapy equipment are favorable
      prognostic factors for DFS and OS and that reducing the overall treatment times
      of radiation to 6 weeks or less and the interval between surgery and radiotherapy
      to less than 3 weeks are simple measures to remarkably improve treatment outcome.

PMID- 21718595
TI  - Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer
      cells.
AB  - Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has
      been extensively implicated in cancer cells; however, its function is not fully
      understood. Our study aimed to determine if oxaliplatin induce autophagy in
      gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis
      induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell
      proliferation was measured using MTT assay, and apoptosis was determined by flow
      cytometry. Protein expression was detected by Western blot. Autophagy was
      observed using fluorescent microscopy. Our results showed that the rate of
      apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20
      MUg/mL oxaliplatin for 24 h, respectively. In addition, caspase activation and
      poly ADP-ribose polymerase (PARP) cleavage were detected. Furthermore, when
      MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate
      LC3 and an increase of LC3-II protein were also detected, indicating the
      activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by
      oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy
      inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of
      cell proliferation and the induction of cell apoptosis. In conclusion,
      oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric
      cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may
      be a new therapeutic option for gastric cancer.

PMID- 21718596
TI  - Correlation of genes associated with drug response to prognosis of large cell
      lung carcinoma.
AB  - Platinum-based chemotherapy remains the main treatment of advanced lung cancer.
      However, platinum resistance has become a major treatment obstacle. Novel
      therapies, particularly tyrosine kinase inhibitors of the epidermal growth factor
      receptor (EGFR-TKI) and agents that target vascular endothelial growth factor
      (VEGF), have improved the treatment. Both chemotherapy and targeted therapy have
      their molecular mechanisms. This study aimed to determine the mutation,
      amplification, or expression status and interrelationships of the epidermal
      growth factor receptor (EGFR), K-Ras proto-oncogene, excision repair cross
      complementation group 1 (ERCC1), and VEGF genes as well as their correlations to
      prognosis of large cell lung carcinoma (LCLC) after EGFR-targeted therapy,
      chemotherapy, and anti-VEGF therapy. EGFR and K-Ras mutations in 60 specimens of
      LCLC were detected by direct DNA sequencing. EGFR, ERCC1, and VEGF protein
      expression was detected by immunohistochemistry (IHC). EGFR gene copy number was
      detected by fluorescence in situ hybridization (FISH). One (1.7%) patient had an
      EGFR L858M point mutation in exon 21, 3 (5.0%) had K-Ras mutations, and 10
      (19.6%) had EGFR amplification (FISH positive). Positive rates of EGFR, ERCC1,
      and VEGF proteins were 38.3%, 56.7%, and 70.0%, respectively. EGFR amplification
      was positively correlated to EGFR protein expression (r = 0.390, P = 0.005). The
      positive rate of VEGF protein was significantly higher in patients with lymph
      node metastasis than in those without (84.6% vs. 58.8%, P = 0.046). No
      significant correlations were observed among the EGFR, K-Ras, ERCC1, and VEGF
      genes. EGFR gene amplification and the low rate of EGFR mutation suggest that
      patients with LCLC are likely to obtain little benefit from anti-EGFR therapies.

PMID- 21718597
TI  - [Bariatric surgery and multidisciplinary treatment for obesity].
AB  - Bariatric surgery is one of the most effective treatment options for obesity.
      Compared with laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux
      en-Y gastric bypass (LRYGB) surgery has demonstrated more benefits and surgical
      risks. Bariatric surgery can result in the decreases in multiple gastrointestinal
      hormone levels, which can partially explain the mechanisms behind weight loss and
      resolution of diabetes after bariatric surgery. The management after bariatric
      surgery should be multidisciplinary and comprehensive, including dietary
      adjustment, physical exercise, behavioral intervention, and drug therapy.

PMID- 21718598
TI  - [Perioperative airway management for patients with morbid obesity].
AB  - The excess fatty tissues on the head, neck, thorax, and abdomen of morbid obese
      patients can impede the patency of the upper airway and impair lung functions.
      Meanwhile, these patients often have comorbidities such as obstructive sleep
      apnea, hypoventilation syndrome, chronic obstructive pulmonary disease, and
      asthma, which may result in difficult airway, intraoperative hypoventilation, and
      postoperative respiratory depression. Therefore, perioperative airway management
      for morbid obese patients may pose a big challenge to anesthesiologists.
      Anesthesiologists should know well about the pathophysiological features of
      respiratory system and grasp rational management principles, so as to improve the
      safety and effectiveness of perioperative airway management and optimize the
      clinical prognosis.

PMID- 21718599
TI  - [Management of nutrition--and endocrine metabolism-related complications of
      bariatric surgery].
AB  - Bariatric surgery has increasingly been applied for patients with severe obesity.
      By dramatically reducing body weight and producing favorable effects on disorders
      in endocrine metabolism, bariatric surgery has shown to be able to lower the
      overall mortality. However, this intervention involves a profound change in
      digestive physiology and may cause nutrition and endocrinal metabolism-related
      severe complications, which mainly result from the deficiency or unbalance of
      macronutrients and micronutrients. Therefore, it is necessary to establish a
      fixed management procedure which includes routine perioperative nutritional
      consultation, regular monitoring, and early preventive nutritional support, so as
      to prevent metabolic complications and achieve better outcomes.

PMID- 21718600
TI  - [Body contouring procedures for massive weight loss patients and their
      complications].
AB  - An increasing number of patients require body contouring procedures after massive
      weight loss. Body contouring can bring better quality of life and increase their
      satisfaction towards weight loss procedures. However, due to the special body
      status after massive weight loss, the complications of body contouring can be
      high. This article briefly describes body contouring procedures and summarizes
      their indications and complications.

PMID- 21718601
TI  - [Obesity and sleep-related breathing disorders].
AB  - Obesity, with an increasing prevalence,has become one of the most common
      metabolic diseases. Obesity is associated with many respiratory diseases,
      especially sleep-related breathing disorders including obstructive sleep apnea
      hypopnea syndrome, obesity hypoventilation syndrome, and overlap syndrome. This
      article reviews the association between obesity and these sleep-related breathing
      disorders.

PMID- 21718602
TI  - [Medical nutritional therapy for obesity].
AB  - Medical nutritional therapy (MNT) is an effective approach for the long-term
      weight control in obese patients. This review describes the processes and
      principles of MNT, nutritional assessment Methods, types of diets, and nutrients
      allowance for obesity management, and also introduces the nutritional
      intervention for bariatric surgery.

PMID- 21718603
TI  - [Anti-obesity drugs: status quo and recent advances].
AB  - Obesity has become a major health problem worldwide. The prevalence and morbidity
      of obesity-related diseases including diabetes, hypertension, cerebro
      cardiovascular diseases, and tumors also have remarkably increased. Treatment of
      obesity poses a challenge for clinicians. Anti-obesity treatment is helpful to
      improve and even reverse obesity-related complications. Diet control and physical
      exercises remain the predominant interventions for obese patients. Anti-obesity
      drugs can be considered in those who respond poorly to behavioral intervention or
      those who have developed obesity-related complications. The commonly used anti
      obesity drugs include gastrointestinal lipase inhibitors and appetite
      suppressants. Glucagon-like peptide 1 has also been found to be effective in
      reducing body weight. Some more drugs are under development, which include
      selective 5-HT 2c agonist, beta3 receptor agonist, and melanocortin receptor 4
      agonist, may also be promising.

PMID- 21718604
TI  - [Individualized exercise training prescription for patients with type 2 diabetes
      mellitus].
AB  - Exercise training plays a critical role in the prevention and control of type 2
      diabetes mellitus (T2DM). New guidelines on exercise training for T2DM patients
      was jointly published by American College of Sports Medicine and American
      Diabetes Association at the end of 2010. In the Guidelines on Prevention and
      Treatment of Type 2 Diabetes Mellitus in China issued by Chinese Diabetes
      Society, the role of exercise training is also clearly defined. The
      implementation of guidelines requires individualized exercise training
      prescription and program. In this article, we review the procedure of
      individualized aerobic exercise training prescription, resistant exercise, safety
      issues, and other relevant topics.

PMID- 21718605
TI  - [Development and interpretation of China medical nutrition therapy guideline for
      diabetes (2010)].
AB  - Nutritional therapy is the basis for all types of diabetes treatment, but has not
      been properly applied due to the lack of scientific criteria. In 2010, the China
      Medical Nutrition Therapy Guideline for Diabetes was successfully developed based
      on the up-to-dated scientific research evidences (especially those from China)
      using Oxford Centre for Evidence-Based Medicine grading system. These guidelines
      cover the nutrition-based prevention and treatment of diabetes and its
      complication as well as the parenteral and enteral nutritional supports, with an
      attempt to improve the quality of life and lower the burdens of diabetes and its
      complications.

PMID- 21718606
TI  - [Comprehensive treatment for type 2 diabetes mellitus].
AB  - The treatment of type 2 diabetes mellitus (T2DM) is traditionally focused on
      glycemic control. In recent years, comprehensive treatment approaches including
      blood sugar control, blood pressure management, and use of antihyperlipidemic
      agents (e.g. statins) and aspirin play critical roles in improving the outcomes
      of T2DM. Some newly developed approaches such as stomach reduction surgery also
      have been applied.

PMID- 21718607
TI  - [Mechanisms of gastrointestinal surgery in treatment of type 2 diabetes].
AB  - Type 2 diabetes can be treated by gastrointestinal surgery, but the underlying
      mechanism is unclear. This review summarizes the possible mechanisms which
      include weight loss, gastrointestinal hormones, foregut hypothesis, hindgut
      hypothesis, adipocytokines, and inflammatory factors.

PMID- 21718608
TI  - [Application of laparoscopic adjustable gastric banding and a multi-disciplinary
      team approach in treatment of morbid obesity and its complications].
AB  - OBJECTIVE: To assess the safety and feasibility of laparoscopic adjustable
      gastric banding (LAGB) and a multi-disciplinary team (MDT) approach in the
      treatment of morbid obesity and its complications. METHODS: We retrospectively
      analyzed the clinical data of 16 patients who underwent LAGB and MDT approach in
      Peking Union Medical College Hospital from October 2009 to February 2011.
      RESULTS: Of these 16 patients, 15 patients completed the 3 month follow up; their
      body weight and body mass index (BMI) decreased significantly after treatment
      (both P=0.000), with an percentage of excess weight loss (%EWL) of (25.7+/-7.4)%.
      Thirteen patients completed 6 month follow up; their body weight and BMI were
      significantly lower than the preoperative levels (both P=0.001), while there were
      no significant difference between the third and sixth month measurements (P=0.103
      and P=0.053, respectively); %EWL of 6 months after operation was significantly
      higher than that of 3 months after operation [(37.0+/-14.7)% vs. (29.1+/
      6.8)%,P=0.042]. Six patients completed 12 month follow up; their body weight and
      BMI decreased significantly at the first 3 months after operation (P=0.007 and
      P=0.005,respectively) and at the second 6 postoperative months (P=0.007 and
      P=0.013,respectively); the BMI of 6 months after operation was significantly
      lower than that of 3 months after operation (P=0.045), but there was no
      significant difference of body weight between the third and sixth month after
      operation (P=0.065); meanwhile, the %EWL increased significantly within the
      second 3 postoperative months from (29.6+/-6.8e% to(42.4+/-14.0e%(P=0.028), and
      also within the second 6 postoperative months (60.4+/-12.6e%(P=0.001). In 9
      patients with pre-operative obstructive sleep apnea hypopnea syndrome, the
      symptom was remarkably resolved in all these 9 patients 3 months after the
      treatment. Of 16 patients with preoperative metabolic syndrome, the condition was
      obviously improved after treatment in 10 patients. Of 9 patients with
      hypertension preoperatively, the blood pressure returned to normal level after
      the withdrawal of antihypertensive agents in 7 patients; in addition, one patient
      had his dose decreased and one patient switched to a milder antihypertensive
      agent. Of 8 patients accompanied with type 2 diabetes, 7 had their antidiabetic
      drugs withdrawn after the blood sugar returned normal and one patient had his
      dose decreased. CONCLUSION: LAGB combined with MDT approach is effective, safe,
      and feasible for treating morbid obesity and its complications.

PMID- 21718609
TI  - [Effectiveness and safety of laparoscopic Roux-en-Y Gastric bypass in treating
      type 2 diabetes mellitus in non-morbidly obese patients].
AB  - OBJECTIVE: To evaluate the effectiveness of laparoscopic Roux-en-Y gastric bypass
      (LRYGB) for achieving type 2 diabetes mellitus (T2DM) remission in patients with
      body mass index (BMI) in the range of 25-35 kg/m(2). METHODS: Twenty-two non
      morbidly obese (BMI: 25-35 kg/m(2)) patients with T2DM underwent LRYGB. The
      changes of BMI, fasting plasma glucose (FPG), and glycosylated hemoglobin (HbA1c)
      levels were recorded, and the prognostic factors were analyzed. RESULTS: All
      these 22 patients successfully underwent LRYGB and were followed up for twelve
      months. Two patients (9.1%) developed complications: one patient had an early
      hemorrhage at the gastrojejunostomy site, and the other had frequent loose stools
      that required revision surgery. At 12 months, 14 patients (63.6%) showed T2DM
      remission, 6 (27.3%) showed glycemic control, and 2(9.1%) showed improvement.
      Compared with the latter two groups, patients in the T2DM remission group had
      significantly higher BMI (P=0.001), younger age (P=0.002), and shorter duration
      of diabetes (P=0.001) before operation. CONCLUSIONS: LYRGB can efficiently and
      safely treat T2DM in non-morbidly obese patients. Early intervention in these
      patients may yield better outcomes.

PMID- 21718610
TI  - [Correlation of adipose volume parameters with anthropometric data in severe
      obese patients].
AB  - OBJECTIVE: To investigate the whole body fat distribution in severe obese
      patients with multi-slice spiral CT, and to explore the correlation between
      adipose volume parameters and anthropometric data. METHODS: Totally 14 severe
      obese patients were enrolled and examined with multi-slice spiral CT. Total
      adipose tissue (TAT) volume and visceral adipose tissue (VAT) volume were
      measured using Volume software. The total, subcutaneous, and visceral adipose
      tissue volumes on umbilical level were also determined. The correlations between
      these parameters and anthropometric data including body weight, body mass index
      (BMI), and waist circumference were analyzed. RESULTS: All scans were performed
      successfully. TAT was significantly correlated with body weight (r=0.7185iP
      =0.004), BMI (r=0.8079iP=0.004), and waist circumference (r=0.7627, P=0.002). VAT
      was mildly correlated with body weight (r=0.5727iP=0.032) and strongly correlated
      with waist circumference (r=0.6707iP =0.001). There was highly significant
      correlation between subcutaneous adipose tissue volume on umbilical level with
      TAT (r=0.8926iP=0.000), and mild correlation between visceral adipose tissue
      volume on umbilical level with VAT (r=0.5949iP=0.025). CONCLUSIONS: Multi-slice
      spiral CT can be applied to evaluate whole body fat distribution in severe obese
      patients. Waist circumference is highly relevant with VAT and therefore can be
      used as a simple parameter for evaluating adipose tissue inside the abdomen.

PMID- 21718611
TI  - [Effect of chlorogenic acid on disordered glucose and lipid metabolism in db/db
      mice and its mechanism].
AB  - OBJECTIVE: To explore the effect of chlorogenic acid on disordered glucose and
      lipid metabolism in db/db mice and its mechanism. METHODS: Thirteen 5-6-week-old
      male db/db mice were randomly divided into db/db-CGA group (n=7) and db/db-CON
      group (n=6), and thirteen 5-6-week-old male db/m mice were randomly divided into
      db/m-CGA group (n=6) and db/m-CON group (n=7). Mice in the CGA groups were
      administrated with CGA 80 mg/(kg.d)by gavage, and mice in the CON groups were
      administrated with PBS in the same volume by gavage. Twelve weeks later, the
      level of biomedical parameters in plasma, liver, and skeletal muscle were
      determined, the concentrations of adiponectin and visfatin in visceral adipose,
      and the mRNA expression of glucose-6-phosphatase (G-6-Pase) and peroxisome
      proliferators-activated receptor-alpha (PPAR-alpha) as well as the protein level
      of PPAR-alpha in liver were detected. RESULTS: Twelve weeks after CGA
      administration, the levels of triglycerides in plasma, liver, and skeletal muscle
      and the fasting plasma glucose in db/db-CGA group were significantly lower than
      those in db/db-CON group(P<0.05). The muscle glycogen level was significantly
      higher than that in db/db-CON group (P<0.05), and the adiponectin concentration
      was significantly higher than that in db/db-CON group ( P<0.01) and lower than
      that in db/m-CGA group(P<0.05). The visfatin concentration in db/db-CGA group was
      significantly lower than that in db/db-CON group (P<0.01) and significantly
      higher than that in db/m-CGA group(P<0.05). The mRNA expression level of G-6-Pase
      was significantly down-regulated in db/db-CGA group when compared with db/db-CON
      group (P<0.05). Both the mRNA and the protein expression levels of PPAR-alpha
      were significantly up-regulated in db/db-CGA group(P<0.05) compared with in db/db
      CON group. CONCLUSION: CGA improves the disordered glucose/lipid metabolism in
      db/db mice, which is speculated to be related with its role in modulating the
      adipokines secretion, up-regulating hepatic PPAR-alpha, and inhibiting G-6-Pase
      expression.

PMID- 21718612
TI  - [Screening for the serum differential proteins of renal cell carcinoma using
      magnetic beads-based matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry].
AB  - OBJECTIVE: To screen for the differential protein peaks of renal cell carcinoma
      (RCC) using magnetic beads-based matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF-MS). METHODS: Serum proteins were profiled
      by magnetic beads (WCX) from 62 RCC patients and 37 patients with benign renal
      space-occupying lesions. Protein peaks were identified by MALDI-TOF-MS. Data were
      analyzed with Biomarker Wizard 3.1 and Biomarker Patterns Software 5.0.
      Diagnostic model for RCC was constructed based on 47 RCC cases and 26 patients
      with benign renal space-occupying lesions. The remaining 26 cases were evaluated
      with blind method. RESULTS: Seven differential protein peaks related to RCC were
      identified (Pbeta0.05). The diagnostic model for RCC constructed by the
      differential protein peaks (m/z 2945.35, 15340.8, 6984.51, and 5819.23) generated
      excellent separation between the RCC and control groups, with a sensitivity of
      83.0% and the specificity of 84.6%. As validated by blind method, the model had a
      sensitivity of 80.0% and a specificity of 81.8%. CONCLUSION: Differential protein
      peaks for RCC can be identified in serum by magnetic beads-based MALDI-TOF-MS,
      which is also valuable for the establishment of a RCC diagnostic model with a
      high sensitivity and specificity.

PMID- 21718613
TI  - [Effect of interleukin 21 and/or interleukin 12 on the antitumor activity of
      peripheral blood mononuclear cells in patients with endometrial cancer].
AB  - OBJECTIVE: To observe the role of interleukin (IL) 21 alone, IL12 alone, and IL21
      plus IL12 for inducing the antitumor activity of peripheral blood mononuclear
      cells (PBMCs) in patients with endometrial cancer. METHODS: PBMCs were isolated
      from peripheral blood in patients with endometrial cancer in vitro, and kept the
      culture with low-level IL2. IL2-stimulated PBMCs were cocultured under different
      conditions (with anti-IL21 antibody, IL21 alone, IL12 alone, or IL21 plus IL12)
      for 72 h. The cytotoxicity of PBMCs was then examined by lactate
      dehydrogenase(LDH) released assay. CD4(+) CD25(+) FOXP3(+) regulatory (Treg) cell
      and CD4(+) IL17A(+) T-helper (Th17) cell proportion were determined with flow
      cytometry. Cell proliferation and apoptosis were measured by cell counting kit
      8(CCK-8)assay and flow cytometry, respectively. RESULTS: In comparison to control
      group, both IL21 and IL12 significantly enhanced the cytotoxicity of PBMCs. The
      IL21 plus IL12 group had superior effect to IL21 alone and IL12 alone. IL21 and
      IL12 significantly decreased the percentages of Treg cells and the rate of PBMCs
      apoptosis. IL21 or IL12 had no significant effect on the differentiation of Th17
      cells and the proliferation of PBMCs. CONCLUSIONS: IL21 and IL12 can enhance the
      cytotoxicity of PBMCs in patients with endometrial cancer, which can be further
      strengthened with treatment of IL21 plus IL12. Such effects may be achieved by
      inhibiting the differentiation of Treg cells and the apoptosis of PBMCs, but not
      by the differentiation of Th17 cell.

PMID- 21718614
TI  - [Association of STEAP4 genetic polymorphisms with insulin resistance in Uygur
      Chinese general population].
AB  - OBJECTIVE: To explore the relationship between six-transmembrane epithelial
      antigen of prostate 4 (STEAP4) genetic polymorphisms and insulin resistance (IR)
      in Uygur Chinese general population. METHODS: In this cross-sectional study on
      the metabolic diseases (e.g. obesity) among Uygur Chinese in Hetian, Xinjiang,
      China,from January to February 2007, 2127 Uygur individuals were enrolled. The
      sample size for IR subjects [homeostasis model assessment for insulin resistance
      (HOMA-IR) >=2.3 65%] was 669, whereas that for non-IR controls was 664 (HOMA
      IR<=1.335%). STEAP4 gene was sequenced in 50 Uygur Chinese individuals with IR
      (HOMA-IR>=2.3). The representative variations were selected from the population
      based on a r(2) cutoff of 0.8 and a minor allele frequency of >5% for case
      control study. RESULTS: Totally 16 variations including 10 novel variations (no
      reported in dbSNP) were identified in 50 Uygur individuals with IR. 7414 G/A
      (rs8122)(P/Pc=0.004/0.012)and 224A/G (rs1981529,
      Gly75Asp)(P/Pc=0.015/0.045)variations were significantly correlated with IR
      phenotype in Uygur subjects. As shown by multiple linear regression analysis, the
      mean values of waist circumference (WC) (P/Pc=0.032/0.256), body mass index (BMI)
      (P/Pc=0.004/0.032), HOMA-IR (P/Pc=0.010/0.08), and fasting insulin
      (P/Pc=0.023/0.184) among A (protection) allele carriers of rs8122 and the mean
      values of WC (P/Pc=0.005/0.040) and BMI (P/Pc=0.002/0.016) among G (protection)
      allele carriers of rs1981529 gradually declined. Haplotype 1 (rs8122 G- rs1981529
      A- rs34741656 G) was significantly associated with a higher prevalence of IR
      (Permutation P=0.021). CONCLUSION: STEAP4 genetic variations are likely to be
      associated with obesity-related insulin resistance in Uygur Chinese general
      population.

PMID- 21718615
TI  - [In vitro effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide on
      differentiation from human adipose-derived mesenchymal stem cells to endothelial
      cells].
AB  - OBJECTIVE: To explore the effect of N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide(W7) on the differentiation from human adipose-derived
      mesenchymal stem cells (hADSCs) to endothelial cells. METHODS: hADSCs were
      cultured with serum-free differential medium containing 40 ng/ml vascular
      endothelial growth factor (VEGF) and 10ng/ml basic fibroblast growth factor
      (bFGF). Cells were divided into control group (differential medium without W7),
      high-dose group (containing 30 MUmol/L W7), medium-dose group (containing 20
      MUmol/L W7), and low-dose group ( containing 10 MUmol/L W7). The hADSCs were
      cultured for 8 days, and then the changes in the phenotypes of von Willebrand
      factor (vWF) and vessel-selective cadherin (VE-Cadherin) were detected by flow
      cytometry (FCM). The intracellular Ca(2+) labeled with Fluo-3 was detected by
      laser confocal microscopy. After hADSCs planting on Matrigel, their angiogenic
      potentials were observed under the inverted phase contrast microscope, and the
      expression of extracellular regulated kinase (ERK) and phosphorylated
      extracellular regulated kinase (p-ERK) were evaluated by Western blot. RESULTS:
      After the hADSCs were cultured for 8 days, compared with the control group, the
      expressions of vWF and VE-Cadherin significantly increased along with the
      decrease of W7 level and the intracellular Ca(2+) also significantly increased
      (Pu0.01). Lumina-like vascular structure was formed in W7 treatment groups, but
      not in the blank control group. Compared with the blank control group, the
      expression of ERK showed no significant in W7 treatment groups (high-, medium-,
      and low-dose groups)(P>0.05); however, along with the decrease of W7 levels, the
      expression of p-ERK significantly increased(P<0.05). CONCLUSION: W7 in proper
      levels can effectively induce the differentiation from hADSCs to endothelium by
      increasing the intracellular Ca(2+) level and thus activating the ERK/MAPK
      pathway.

PMID- 21718616
TI  - [Acceptability of male circumcision among male miners in Baise of Guangxi].
AB  - OBJECTIVE: To investigate the acceptability of male circumcision among male
      miners in Baise, Guangxi, China. METHODS: A questionnaire-based survey on the
      willingness to be circumcised (WTC) and its influential factors were conducted
      among Guangxi male miners recruited by random cluster sampling. RESULTS: Of 569
      subjects who were surveyed, 143 (25.13%) expressed their willingness to be
      circumcised. Univariate analysis showed that marital status, education level, and
      the awareness of the hazards of phimosis and redundant prepuce and reasons for
      circumcision were significantly different between WTC group and the non-WTC group
      (all P<0.05). Furthermore, the incidence of phimosis or redundant prepuce also
      significantly differed between these two groups (P=0.0001). Logistic regression
      analysis found marital status (OR=0.498i95%CI=0.272-0.913), history of foreskin
      disease (OR=8.181, 95%CI=4.252-15.741), and awareness of the risk that a
      redundant prepuce may cause smegma (OR=1.713i95%CI=1.090-2.693) were
      significantly correlated with the male miners WTC. CONCLUSIONS: Male miners in
      this area have low WTC. Education on the basic knowledge of acquired
      immunodeficiency syndrome and circumcision may help promote the application of
      circumcision.

PMID- 21718617
TI  - [Effectiveness of Ganoderma lucidum preparation in treating simian acquired
      immune deficiency syndrome].
AB  - OBJECTIVE: To explore the effectiveness of the traditional Chinese herbal
      medicine Lingzhi (Ganoderma lucidum) preparation in treating simian acquired
      immune deficiency syndrome (SAIDS). METHODS: Five female adult Chinese rhesus
      monkeys were inoculated rectally with SIVmac239, and were all diagnosed as SAIDS
      by laboratory and clinical examinations 17 months later. Of these 5 monkeys, 3
      (#393, #374, and #381; treatment group) were orally administered with Ganoderma
      lucidum (2 spores powder capsules plus 2 spores oil capsules on a daily basis),
      and the remaining other two monkeys (#348 and #361) served as control and did not
      receive treatment. RESULTS: Animal #393 (treatment group), #361 (control group)
      and #348 (control group) died of SAIDS (opportunity infection) 3.5 months, 6
      months, and 11 months later, respectively. Two animals (#374 and #381) survived.
      The necropsy revealed depletion and/or exhaustion of their lymphoid tissue. In
      the monkey #374, the peripheral CD4(+) T lymphocyte increased by 30% in the 6(th)
      month compared with the baseline level and then fluctuated. The plasma viral load
      gradually fell and reached about 1 log(10) in the treatment group, but remained
      stable in the control group. As shown by pathological examinations, the lymph
      node and spleen of monkeys #374 (treatment group) and #381 (treatment group)
      showed rehabilitation and reconstruction in the lymphatic tissue, thymus, nerve
      tissue of gyrus hippocampi, pituitary gland, pineal body, thyroid gland, adrenal
      gland, and ovary. In the control group, however, animals experienced depletion of
      lymph nodes, atrophy of spleen, disappearance of thymus, and other disorders in
      endocrine organs. CONCLUSION: Ganoderma lucidum preparation may have certain
      protective effect on the immune system, nervous system, and endocrine system of
      monkeys with SAIDS.

PMID- 21718618
TI  - [Diagnosis and treatment of 166 patients with early gastric cancer].
AB  - OBJECTIVE: To summarize our experiences in the diagnosis and treatment of early
      gastric cancer (EGC). METHODS: The clinicopathological data of the 166 EGC
      inpatients who were treated in our hospital from January 1999 to January 2009
      were retrospectively analyzed and their treatment outcomes were followed up.
      RESULTS: Surgical treatment for ECG accounted for 9.04% (176/1946) among all the
      surgeries performed for gastric cancers. Among the analyzed 166 cases, 9
      asymptomatic patients were diagnosed by routine examination, 29 (17.47%) had a
      history of gastric ulcer or chronic gastritis, and 20 (12.05%) had a family
      history of esophageal or gastric cancer. Of 64 patients who received double
      contrast gastric X-ray examination, 57 patients (89.06%) were found to be with
      abnormalities. Endoscopy revealed lesions in lower third, middle third, and upper
      third of the stomach in 115 patients (69.28%), 26 patients (15.66%), and 25
      patients (15.06%), respectively. A total of 126 patients received D(0) or D1
      operations and 40 patients received operations more than D+1 operation. As shown
      by post-operative pathological examinations, the mean diameter of the lesions was
      (2.52+/-1.62) cm; 75 patients (45.18%) had mucosal gastric cancer, 91 (54.82%)
      had submucosal gastric cancer, 20 patients with submucosal gastric cancer had
      lymph node metastasis, and 8 patients had lymphatic vessel involvement. The
      overall 5-year survival rate was 70.0% and 89.7% among patients with or without
      lymph node metastasis (P=0.002). Univariate analysis revealed that depth of tumor
      invasion (submucosa) and lymphatic vessel involvement were significantly
      correlated with lymph node metastasis (P=0.000, P=0.001). Multivariate analysis
      showed that lymphatic vessel involvement was significantly correlated with lymph
      node metastasis (odds ratio: 15.67; 95% confidence interval, 3.40-72.14).
      CONCLUSIONS: The proportion of EGC patients undergoing gastrectomy is relatively
      low among all gastric cancer patients. Lymph node metastasis is a key prognostic
      factor for EGC. A proper staging of gastric cancer, a precise evaluation of the
      depth of infiltration, and appropriate and standardized treatment are important
      to improve the outcomes.

PMID- 21718619
TI  - [Clinical symptoms in 455 hyperparathyroidism patients].
AB  - OBJECTIVE: To analyze the clinical symptoms of patients with hyperparathyroidism.
      METHODS: The clinical data of 455 patients with hyperparathyroidism who were
      treated in Peking Union Medical College Hospital from October 1974 to January
      2009 were retrospectively analyzed. RESULTS: Out of these 455 patients, there
      were 156 men (34.3%) and 299 women (65.7%), and the male/female ratio was 1:1.92.
      The mean onset age was (40.33+/-16.61) years (range: 5-86 years). Most patients
      (n=372, 81.8%) with skeletal manifestations, of whom 283 patients (62.2%)
      presented with ostealgia. The second most common symptom (n=252, 55.4%) was in
      urinary system, of whom 162 patients (35.6%) had nephrolithiasis. There were 200
      patients (44.0%) with digestive system symptoms and 54 patients (11.9%) with
      neuropsychological symptoms. Twenty-one patients (4.6%) had asymptomatic
      hyperparathyroidism. There were 133 patients (29.2%) with decreased body height,
      and the mean decrease was(6.23+/-5.02)cm. Forty-nine patients (10.8%) presented
      with hypercalcemia crisis. CONCLUSIONS: Women are more susceptible to
      hyperparathyroidism, which is featured by symptoms in skeletal system, urinary
      system, and digestive system. The asymptomatic hyperparathyroidism is relatively
      rare, which should be carefully considered during clinical practice.

PMID- 21718622
TI  - A bit of history.

PMID- 21718620
TI  - [Application of valplast dentures in the temporary restoration of single missing
      anterior tooth].
AB  - OBJECTIVE: To evaluate the value of valplast dentures in the temporary
      restoration of single missing anterior tooth. METHODS: Totally 76 patients who
      needed temporary restoration of single missing anterior tooth were involved and
      equally divided into two groups according to their own choices of procedures:
      group A, with valplast dentures as their temporary dentures and group B, with
      conventional removable partial dentures as their temporary dentures. Meanwhile,38
      patients who had their single anterior teeth pulled out and did not need
      temporary dentures were enrolled as control group without any temporary
      restoration, and impressions were taken immediately before the temporary dentures
      were used (2 weeks after tooth extraction) and before the initiation of permanent
      restorations (97-100 days after tooth extraction).The heights of clinical crowns
      of the adjacent teeth were also recorded twice from plaster models made from the
      impressions.The height of labial gingiva recession was calculated as the
      difference between the two heights recorded. RESULTS: The height differences of
      clinical crowns of the adjacent teeth was 0.5mm (range: 0.0-1.2mm) in group A,
      which was significantly larger than those in group B [0.0mm;(range: 0.0
      0.6mm)](P<0.05) and in group C[0.0mm;(range: 0.0-0.4mm)](P<0.05).However, the
      difference was not significant between group B and group C (P>0.05). CONCLUSION:
      Application of valplast denture as temporary denture may cause labial gingival
      recession of the adjacent teeth, and therefore is not suitable for the
      restoration of single missing anterior tooth.

PMID- 21718623
TI  - President's message: old guard, new blood.

PMID- 21718624
TI  - Hurry up and wait. The experiences of young women in rural Nova Scotia accessing
      specialized care.
AB  - INTRODUCTION: This study explored experiences of waiting to access specialized
      health care among young women living in selected rural communities on the south
      shore of Nova Scotia. We asked women about the challenges they faced during wait
      times and how they perceived the impact of these experiences on their health.
      METHODS: We conducted qualitative interviews with 10 women aged 21-37 years. We
      used thematic analysis to identify common experiences among participants.
      RESULTS: Some women expressed feelings of frustration about waiting, but others
      resigned themselves to the wait. Women reported challenges such as caregiving for
      ailing family members who waited for care. Some women took control of their
      situation by accessing private health care or what they called "the next best
      thing" (e.g., care from alternative health providers), although in some cases
      this was financially costly. A few women sought assistance through support
      networks. Many women reported that wait times affected their health. CONCLUSION:
      Our results support previous research indicating that young rural women's
      caregiving roles and support networks influence their experiences with wait
      times. Our research indicates that waiting to access specialized care can be
      financially costly for some women and may also affect their health.

PMID- 21718626
TI  - The occasional teacher. Part 4: feedback and evaluation.

PMID- 21718625
TI  - An evaluation of the Acute Critical Events Simulation (ACES) course for family
      medicine residents.
AB  - INTRODUCTION: A 2-year residency must prepare family physicians to provide a
      broad range of services. In many settings, especially rural and remote practices,
      family physicians provide emergency and inpatient care and thus encounter
      critically ill patients. Evidence of the importance of early recognition and
      aggressive intervention in critical illness is growing. However, opportunities to
      safely practise critical care skills during residencies are limited. METHODS: The
      2-day Acute Critical Events Simulation (ACES) course was offered to all family
      medicine residents at the University of Ottawa in 2009. The course included
      lectures, case discussions, hands-on task training and a half-day of high
      fidelity simulation. Its aims were to enhance the abilities of residents in
      family medicine to recognize signs of critical illness, to teach competencies in
      the early resuscitation and care of such patients, and to increase residents'
      confidence to include inpatient and emergency care in their practices, or to
      practise in a rural or remote setting. A postcourse questionnaire, which included
      Likert-scale and open-ended questions, was distributed to all participants.
      RESULTS: Thirty-seven participants completed the survey. The ACES course was
      exceptionally well-received by participants, who reported increases in confidence
      and perceived competence, as well as intentions to change practice. The course
      appeared to increase participants' confidence to work in rural or remote areas
      and include inpatient or emergency medicine services in their practices.
      CONCLUSION: The ACES course achieved its aims, and participants reported positive
      outcomes. This highly interactive, simulation-based program may help prepare
      residents for work in rural or remote communities with critically ill patients.

PMID- 21718627
TI  - The occasional management of narcotic exposure in neonates.

PMID- 21718628
TI  - Country cardiograms case 40.

PMID- 21718629
TI  - Professional isolation in small rural surgical programs: the need for a virtual
      department of operative care.

PMID- 21718630
TI  - Rural electives: a clinical and community experience.

PMID- 21718631
TI  - Clinical courage.

PMID- 21718632
TI  - Clinical courage.

PMID- 21718634
TI  - [" Self-eating " to survive - coordinated regulation of autophagy by nutrients].

PMID- 21718635
TI  - [The interaction of Crohn's disease-associated Escherichia coli to Peyer's
      patches of the intestinal mucosa involves long polar fimbriae].

PMID- 21718636
TI  - [Conservation of cyclophilin A interaction with the capsid of prehistoric
      lentiviruses].

PMID- 21718637
TI  - [TgROM4 and TgAMA1: a checkpoint in parasite replication].

PMID- 21718638
TI  - [Mendelian susceptibility to mycobacterial infections and defect in macrophages
      respiratory burst].

PMID- 21718639
TI  - [Language is not uniquely human, monkeys " saying "!].

PMID- 21718640
TI  - [Rescue of nonsense mutated p53 by readthrough leads to apoptosis in cancers
      cells].

PMID- 21718641
TI  - [Humanized mice for the study of hepatitis C].

PMID- 21718642
TI  - [The rounding of mitotic cells].

PMID- 21718643
TI  - [Human diseases and NOTCH receptors].

PMID- 21718644
TI  - [Discovering a new functional neurogenic zone: the vestibular nuclei of the
      brainstem].
AB  - The adult mammal brain is mostly considered as non-neurogenic, except in the
      subventricular zone of the lateral ventricles and the subgranular zone of the
      dentate gyrus, where ongoing neurogenesis occurs. However, anti-neurogenic
      influences can be removed in pathological conditions or after specific injury.
      That is what happens in a model of unilateral vestibular neurectomy (UVN) that
      mimics human pathology in adult cats. We showed for the first time that a UVN
      promoted an intense reactive cell proliferation in the deafferented vestibular
      nuclei located in the brainstem. The new cells survived up to one month,
      differentiated into glial cells - microglia or astrocytes - or GABAergic neurons,
      so highlighting a GABAergic neurogenesis. Surprisingly, we further showed that
      post-UVN reactive cell proliferation contributed successfully to fine restoration
      of vestibular posturo-locomotor functions. In conclusion, these pioneering
      studies bring new pieces of a promising puzzle in both stem cell and vestibular
      therapy domains.

PMID- 21718645
TI  - [N-6 fatty acids and cardiovascular health: dietary intake recommendations].
AB  - Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their critical
      role in many physiological functions and reduce risks of cardiovascular disease
      (CVD). However, some argue that excessive consumption of n-6 PUFA may lead to
      adverse effects on health and therefore recommend reducing dietary n-6 PUFA
      intake or fixing an upper limit. Epidemiological studies show that n-6 PUFA
      dietary intake significantly lowers blood LDL-cholesterol levels. In addition, n
      6 PUFA intake lower several cardiovascular risk factors such as blood pressure,
      inflammatory markers, haemostatic parameters and obesity. Data from prospective
      cohort and interventional studies converge towards a specific protective role of
      dietary n-6 PUFA intake, in particular linoleic acid, against CVD. In regards to
      studies examined in this narrative review, recommendation for n-6 PUFA intake
      above 5%, and ideally about 10% of total energy appears justified for the
      prevention of ischemic heart disease.

PMID- 21718646
TI  - [The IKKepsilon kinase in breast cancer: from oncogenesis to treatment
      resistance].
AB  - The IKKepsilon kinase, an atypical member of the IKK family of kinases, was
      recently identified as an oncogene overexpressed in over 30% of breast cancers.
      Besides its role in the regulation of the NF-kappaB transcription factor, which
      is well recognized for its implication in the development of breast cancers,
      IKKepsilon was shown to phosphorylate numerous targets. Analysis of the
      phosphorylation of some of these substrates in the context of breast cancer
      highlighted new oncogenic signaling pathways that constitute potential targets
      for new therapies. Interestingly, IKKepsilon is involved in the development of
      resistance to Tamoxifene. Thus, IKKepsilon is a promising therapeutic target for
      newly developed breast cancer treatment.

PMID- 21718647
TI  - [CYLD deubiquitinase as a recurrent target in oncogenic processes].
AB  - CYLD deubiquitinase has been originally defined as a tumor suppressor based
      exclusively on genetic findings. Indeed, inactivation of CYLD in humans results
      in familial cylindromatosis and multiple trichoepithelioma, two pathologies
      characterized by the development of tumors originating specifically from the skin
      appendages. A set of recent publications has revealed that recurrent inactivation
      of CYLD occurs through diverse mechanisms in several forms of cancer,
      unequivocally confirming its tumor suppressor function. This property is
      associated with the critical role played by CYLD in negatively regulating several
      signaling pathway, among them the NF-kappaB signaling pathway.

PMID- 21718648
TI  - [Serum autoantibodies profiling and early-stage cancer detection].
AB  - It is now well established that an immune response to cancer is elicited in
      humans, as demonstrated in part by the identification of autoantibodies against a
      number of tumor-associated antigens in sera from patients with different types of
      cancer. During these past few years, proteomic approaches have been developed to
      identify tumor-associated antigens and their cognate autoantibodies. Detection of
      a panel of serum autoantibodies has thus been proposed as a new method for early
      cancer diagnosis. Early detection seems to be particularly adequate in high-risk
      populations, such as heavy smokers for lung cancer or in women with high
      mammographic density for breast cancer. In this review, we highlight the features
      of serum autoantibody biomarkers and outline the proteomic strategies employed to
      identify and validate their use in clinical practice for cancer screening and
      diagnosis. We particularly emphasize the clinical utility of autoantibody
      signatures, using the examples of lung and breast cancer. Finally, we discuss the
      challenges remaining for clinical validation.

PMID- 21718649
TI  - [Neuroimaging of psychiatric and pedopsychiatric disorders].
AB  - Over the last two decades, imaging techniques have allowed to establish the
      cerebral neurophysiologic correlates of psychiatric disorders and have
      highlighted the impact of psychopathologic events, therapeutic drugs, addictions,
      on the growth and plasticity of brain. In this review, we intend to illustrate
      how neuroimaging has improved our knowledge of such alterations in brain
      maturation (schizophrenia, autistic disorders), fronto-limbic (depressive
      syndromes) or fronto-striatal (compulsive disorders) regions in psychiatric
      illnesses, but also in psychopharmacology, or pedopsychiatry. Statistically
      significant alterations in the structure and/or function of brain are detected in
      all psychiatric disorders and these are often detectable already during childhood
      or teenage. Furthermore, neuroimaging has allowed to underline the importance of
      cerebral networks specific to each disorder, but also to uncover those which are
      common to different diseases provided that they share common clinical or
      cognitive features. Besides their value in basic research, neuroimaging findings
      have been key in changing the perception that society has of these diseases which
      contributed to their therapeutic approach.

PMID- 21718650
TI  - [Impact of the pathology in modern medicine].
AB  - In this review, the authors emphasize the pivotal role of the pathology in the
      setting of a revolution which progressively transforms medical sciences into
      basic sciences. Several key aspects of this specialty will be discussed together
      with the main perspectives in the fields of oncologic disorders.

PMID- 21718651
TI  - [Genetic predisposition to breast and ovarian cancer: importance of test
      results].
AB  - Oncogenetic consultations and predictive BRCA1/2 testing are intertwined
      processes and the specific impact of these genetic tests if performed alone
      through direct-to-consumer offers remains unknown. Noteworthy, the expectations
      of patients vary with their own status, whether they are affected or not by
      breast cancer at the time genetic testing is performed. The prescription of
      genetic tests for BCRA mutations has doubled in France between 2003 and 2009.
      There is a consensus on the fact that genetic results disclosure led to a
      significant increase in the knowledge and understanding that the patients have of
      the genetic risk and also changed the medical follow-up of these patients.
      Evaluating the psychological burden of tests disclosure did not reveal any major
      distress in patients who are followed by high-quality multidisciplinary teams.
      Longitudinal cohorts studies have now evaluated the perception and behaviour of
      these patients, and observed sociodemographic as well as geographic and
      psychosocial differences both in the acceptation of prophylactic strategies such
      as surgery, and time to surgery.

PMID- 21718652
TI  - [Federal judge and government of the United States against gene patenting].

PMID- 21718653
TI  - [Your DNA will talk to us!].

PMID- 21718654
TI  - [MicroRNA control biosynthesis of motile cilia in vertebrates].

PMID- 21718655
TI  - Synthesis, crystal structures and spectroscopy of meclofenamic acid and its metal
      complexes with manganese(II), copper(II), zinc(II) and cadmium(II).
      Antiproliferative and superoxide dismutase activity.
AB  - Some new complexes of meclofenamic acid (N-(2,6-dichloro-m-tolyl)anthranilic
      acid), Hmeclo (1), with potentially interesting biological activities are
      described. Complexes [Mn(meclo)(2)] (2), [Cu(meclo)(2)(H(2)O)(2)] (3),
      [Zn(meclo)(2)(H(2)O)(2)] (4) and [Cd(meclo)(2)(H(2)O)(2)] (5) were prepared and
      structurally characterized by means of vibrational, electronic and (1)H and (13)C
      NMR spectroscopies. The crystal structure of complexes
      [Cu(4)(meclo)(6)(OH)(2)(DMSO)(2)]2DMSO (3a) and [Cd(meclo)(2)(DMSO)(3)] (5a) have
      been determined by X-ray crystallography. Complex (3a) is a centrosymmetric
      tetramer built up around the planar cyclic Cu(2)(OH)(2) unit. Complex 5a is
      mononuclear seven-coordinated complex with the meclofenamato ligand behaving as a
      bidentate deprotonated chelating ligand. Intra and intermolecular hydrogen bonds
      stabilize these two structures, while the crystal packing is determined by pi-pi
      and C-H--pi interactions. Meclofenamic acid and its metal complexes have been
      evaluated for antiproliferative activity in vitro against the cells of three
      human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer
      cell line), and A-549 (non-small cell lung carcinoma), and a mouse fibroblast L
      929 cell line. Complex 5 exhibits the highest selectivity against MCF-7 and 4
      shows the highest selectivity against T-24. Complexes 2-5 were found to be more
      potent cytotoxic agents against T-24 and complex 5 against MCF-7 cancer cell
      lines than the prevalent benchmark metallodrug, cis-platin. The superoxide
      dismutase activity was measured by the Fridovich test which showed that complex
      [Cu(meclo)(2)(H(2)O)(2)] is a good superoxide scavenger.

PMID- 21718656
TI  - Exploring the catalytic potential of the 3-His mononuclear nonheme Fe(II) center:
      discovery and characterization of an unprecedented maltol cleavage activity.
AB  - Mononuclear nonheme iron enzymes (MNHEs) catalyze a range of very diverse
      reactions in O(2) metabolism, but they share a common principle active-site
      organization. To investigate a putative catalytic promiscuity of these enzymatic
      metal centers, we studied the reactivity of the 3-His ligated metal center of
      diketone cleaving enzyme (Dke1) toward non-native substrates, with a focus on
      alternative O(2) dependent reactions. From a screening approach, which aims at
      eliminating steric factors by including minimal substrate-substructures, three
      alternative, 'non-beta-dicarbonyl-cleavage' reactions are identified, among them
      an unprecedented oxygenation of maltol. Maltol cleavage is characterized by
      steady state and fast kinetic measurements and shows an O(2) concentration
      dependent rate determining step k(cat)/K(M)(O(2)) of 0.3mM(-1)s(-1) and a strict
      coupling of O(2) reduction and substrate oxidation. Furthermore, the catalytic
      potential of the 3-His metal center for O(2) dependent catechol ring-cleavage and
      phenylpyruvate oxidation (PP) is demonstrated.

PMID- 21718657
TI  - Generation and characterization of neurogenin1-GFP transgenic medaka with
      potential for rapid developmental neurotoxicity screening.
AB  - Fish models such as zebrafish and medaka are increasingly used as alternatives to
      rodents in developmental and toxicological studies. These developmental and
      toxicological studies can be facilitated by the use of transgenic reporters that
      permit the real-time, noninvasive observation of the fish. Here we report the
      construction and characterization of transgenic medaka lines expressing green
      fluorescent protein (GFP) under the control of the zebrafish neurogenin 1 (ngn1)
      gene promoter. Neurogenin (ngn1) is a helix-loop-helix transcription factor
      expressed in proliferating neuronal progenitor cells early in neuronal
      differentiation and plays a crucial role in directing neurogenesis. GFP
      expression was detected from 24 h post-fertilization until hatching, in a spatial
      pattern consistent with the previously reported zebrafish ngn1 expression.
      Temporal expression of the transgene parallels the expression profile of the
      endogenous medaka ngn1 transcript. Further, we demonstrate that embryos from the
      transgenic line permit the non-destructive, real-time screening of ngn1 promoter
      directed GFP expression in a 96-well format, enabling higher throughput studies
      of developmental neurotoxicants. This strain has been deposited with and
      maintained by the National BioResource Project and is available on request
      (http://www.shigen.nig.ac.jp/medaka/strainDetailAction.do?quickSearch=true&strain
      d=5660).

PMID- 21718658
TI  - Construction and analysis of liver suppression subtractive hybridization library
      of silver carp (Hypophthalmichthys molitrix) intraperitoneally injected with
      microcystin-LR.
AB  - Microcystin-LR (MC-LR) is the most frequently studied cyclic heptapeptide
      hepatotoxin produced by cyanobacteria. The toxin accumulates rapidly in the liver
      where it exerts most of its damage, but the molecular mechanisms behind its
      toxicity remain unclear. Here, suppression subtractive hybridization (SSH) was
      used to identify alterations in gene transcription of the silver carp
      (Hypophthalmichthys molitrix) after exposure to MC-LR. After hybridization and
      cloning, the forward and reverse subtractive cDNA libraries were obtained. At
      random, 150 positive clones (70 forward and 80 reverse) were selected and
      sequenced from the subtractive libraries, which gave a total of 88 gene fragment
      sequences (48 forward and 40 reverse). Sequencing analysis and homology searches
      showed that these ESTs represented 75 unique genes and 13 duplicates. Of the 75
      unique genes, 38 shared high homology with fish genes of known functions,
      including immune-related genes, transporters and some involved in cell
      metabolism. Four sequenced genes (Fs59, Fs70, Rs2 and Rs15) were analyzed further
      using semi-quantitative RT-PCR. The genes from the forward library (Fs59 and
      Fs70) were found to be transcriptionally upregulated, while the genes from the
      reverse library (Rs2 and Rs15) were found to be transcriptionally downregulated.
      These results confirmed the successful construction of the subtractive cDNA
      library that was enriched for genes that were differentially transcribed in the
      silver carp liver challenged with MC-LR.

PMID- 21718659
TI  - Translational responses and oxidative stress of mussels experimentally exposed to
      Hg, Cu and Cd: one pattern does not fit at all.
AB  - Certain metals, like Hg, Cu and Cd, are capable of down-regulating protein
      synthesis in several marine organisms, including Mytilus galloprovincialis.
      Nevertheless, due to the complexity of the environmental stress, it is difficult
      to evaluate the influence of individual metals on protein synthesis via field
      studies. To bypass this difficulty, experimental studies were carried out on M.
      galloprovincialis exposed in aquarium for 15 days to one of three selected metal
      salts, HgCl(2), CuCl(2) and CdCl(2). Polysome profile was determined in digestive
      gland extracts of the exposed mussels as a way of measuring the functional status
      of ribosomes, superoxide radical production and lipid peroxidation as indicators
      of oxidative stress, metallothionein content as a metal detoxification index, and
      superoxide dismutase activity as a free radicals-scavenging index. Exposure of
      mussels to Hg(2+) or Cu(2+) resulted in a concentration- and time-dependent
      decrease in the polysome content of digestive gland cells, which at 15th day of
      exposure and at the highest metal concentrations tested, was 32% and 19% of the
      control, respectively. Both metals, at the concentrations used (<40 MUg/L), did
      not significantly influence the oxidative stress biomarkers. By contrast, Cd(2+)
      treatment significantly induced superoxide radical production and lipid
      peroxidation in digestive gland cells, hinting that mussels suffered from
      oxidative stress. Polysome levels in Cd(2+)-exposed mussels were initially
      decreased by day 5 in digestive gland cells and then elevated to reach nearly the
      control levels by 15 days of exposure. Elevated protein synthesis was associated
      with significantly increased production of metallothioneins, whereas such
      increase was not recorded in Hg(2+)- or Cu(2+)-exposed mussels. Interestingly,
      the ribosome efficiency at initiating protein synthesis followed a similar
      pattern of polysome alterations, a fact suggesting that regulation of protein
      synthesis mainly occurred at the initiation phase of translation. Overall, these
      results suggest that the effect of each metal on protein synthesis is
      idiosyncratic and depends on its ability to induce specific cellular defense
      mechanisms against oxidative stress.

PMID- 21718660
TI  - Effects of ocean acidification on trace element accumulation in the early-life
      stages of squid Loligo vulgaris.
AB  - The anthropogenic release of carbon dioxide (CO(2)) into the atmosphere leads to
      an increase in the CO(2) partial pressure (pCO(2)) in the ocean, which may reach
      950 MUatm by the end of the 21st century. The resulting hypercapnia (high pCO(2))
      and decreasing pH ("ocean acidification") are expected to have appreciable
      effects on water-breathing organisms, especially on their early-life stages. For
      organisms like squid that lay their eggs in coastal areas where the embryo and
      then paralarva are also exposed to metal contamination, there is a need for
      information on how ocean acidification may influence trace element
      bioaccumulation during their development. In this study, we investigated the
      effects of enhanced levels of pCO(2) (380, 850 and 1500 MUatm corresponding to
      pH(T) of 8.1, 7.85 and 7.60) on the accumulation of dissolved (110m)Ag, (109)Cd,
      (57)Co, (203)Hg, (54)Mn and (65)Zn radiotracers in the whole egg strand and in
      the different compartments of the egg of Loligo vulgaris during the embryonic
      development and also in hatchlings during their first days of paralarval life.
      Retention properties of the eggshell for (110m)Ag, (203)Hg and (65)Zn were
      affected by the pCO(2) treatments. In the embryo, increasing seawater pCO(2)
      enhanced the uptake of both (110m)Ag and (65)Zn while (203)Hg showed a minimum
      concentration factor (CF) at the intermediate pCO(2). (65)Zn incorporation in
      statoliths also increased with increasing pCO(2). Conversely, uptake of (109)Cd
      and (54)Mn in the embryo decreased as a function of increasing pCO(2). Only the
      accumulation of (57)Co in embryos was not affected by increasing pCO(2). In
      paralarvae, the CF of (110m)Ag increased with increasing pCO(2), whereas the
      (57)Co CF was reduced at the highest pCO(2) and (203)Hg showed a maximal uptake
      rate at the intermediate pCO(2). (54)Mn and (65)Zn accumulation in paralarvae
      were not significantly modified by hypercapnic conditions. Our results suggest a
      combined effect of pH on the adsorption and protective properties of the eggshell
      and of hypercapnia on the metabolism of embryo and paralarvae, both causing
      changes to the accumulation of metals in the tissues of L. vulgaris.

PMID- 21718661
TI  - Identifying and modeling patterns of tetrapod vertebrate mortality rates in the
      Gulf of Mexico oil spill.
AB  - The accidental oil spill in the Gulf of Mexico in 2010 has caused perceptible
      damage to marine and freshwater ecosystems. The large quantity of oil leaking at
      a constant rate and the long duration of the event caused an exponentially
      increasing mortality of vertebrates. Using data provided by NOAA and USFWS, we
      assessed the effects of this event on birds, sea turtles, and mammals. Mortality
      rates (measured as the number of carcasses recorded per day) were exponential for
      all three groups. Birds were the most affected group, as indicated by the
      steepest increase of mortality rates over time. For sea turtles and mammals, an
      exponential increase in mortality was observed after an initial delay. These
      exponential behaviors are consistent with a unified scenario for the mortality
      rate for tetrapod vertebrates. However, at least for mammals, pre-spill data seem
      to indicate that the growth in the mortality rate is not entirely a consequence
      of the spill.

PMID- 21718662
TI  - Changes in gene transcription and whole organism responses in larval fathead
      minnow (Pimephales promelas) following short-term exposure to the synthetic
      pyrethroid bifenthrin.
AB  - The combination of molecular and whole-organism endpoints in ecotoxicology
      provides valuable information about the ecological relevance of sublethal
      stressor effects in aquatic ecosystems such as those caused by the use of
      insecticides and translocation of their residues into surface waters. This study
      contributes knowledge about the sublethal effects of a common use insecticide,
      the synthetic pyrethroid bifenthrin, on larval fathead minnow (Pimephales
      promelas). Transcriptomic responses, assessed by quantitative real-time PCR,
      combined with individual effects on swimming performance were used to estimate
      the ecological relevance of insecticide impacts. Significant transcriptomic
      responses were observed at 0.07 MUg L(-1) bifenthrin (lowest observed effect
      concentration, LOEC) but mostly followed a biphasic rather than a linear dose
      response with increasing concentration. Transcript patterns for genes involved in
      detoxification, neuromuscular function and energy metabolism were linked to an
      impairment of swimming performance at >=0.14 MUg L(-1) bifenthrin. With
      increasing treatment concentration, a significant down-regulation was observed
      for genes coding for cyp3a, aspartoacylase, and creatine kinase, whereas
      metallothionein was up-regulated. Additionally, bifenthrin induced endocrine
      responses as evident from a significant up-regulation of vitellogenin and down
      regulation of insuline-like growth factor transcripts. Recovery occurred after 6
      days and was dependent on the magnitude of the initial stress. During the
      recovery period, down-regulation of vitellogenin was observed at lowest exposure
      concentrations. The data presented here emphasize that links can be made between
      gene transcription changes and behavioral responses which is of great value for
      the evaluation and interpretation of biomarker responses.

PMID- 21718663
TI  - Posttraumatic growth among children and adolescents: a systematic review.
AB  - Stress and trauma research has traditionally focused on negative sequelae of
      adversity. Recently, research has begun to focus on positive outcomes,
      specifically posttraumatic growth (PTG) - "positive change experienced as a
      result of the struggle with trauma" - which emphasizes the transformative
      potential of one's experiences with highly stressful events and circumstances.
      The positive changes of PTG are generally thought to occur in five domains: new
      possibilities, relating to others, personal strength, appreciation of life, and
      spiritual change. The study of PTG has, for the most part, been centered on
      adults, and not until very recently has there been sufficient research on PTG
      among children and adolescents to justify a review. The current systematic review
      of the literature on PTG among children and adolescents included 25 studies that
      tested associations between PTG and conceptually-relevant variables found to be
      associated with PTG in adults and hypothesized to play similar roles in young
      people, including environmental characteristics, distress responses, social
      processes, psychological processes, positive outcomes, and demographic variables.
      Links were made between a theoretical model of PTG among youth and findings of
      the current review. Limitations and recommendations for future research are
      discussed.

PMID- 21718664
TI  - Targeting STAT3 in hepatocellular carcinoma: sorafenib again....

PMID- 21718665
TI  - HCV and the hepatic lipid pathway as a potential treatment target.
AB  - Atherosclerosis has been described as a liver disease of the heart [1]. The liver
      is the central regulatory organ of lipid pathways but since dyslipidaemias are
      major contributors to cardiovascular disease and type 2 diabetes rather than
      liver disease, research in this area has not been a major focus for
      hepatologists. Virus-host interaction is a continuous co-evolutionary process [2]
      involving the host immune system and viral escape mechanisms [3]. One of the
      strategies HCV has adopted to escape immune clearance and establish persistent
      infection is to make use of hepatic lipid pathways. This review aims to: * update
      the hepatologist on lipid metabolism * review the evidence that HCV exploits
      hepatic lipid pathways to its advantage * discuss approaches to targeting host
      lipid pathways as adjunctive therapy.

PMID- 21718666
TI  - "The city of Hepar": rituals, gastronomy, and politics at the origins of the
      modern names for the liver.
AB  - Medical etymology sometimes provides unexpected information about health concepts
      and medical practice in different times and cultures. We conducted an
      etymological analysis of the terms used to indicate "liver" in Germanic and
      Romance languages. The Greek word "hepar" was originally connected to the concept
      of "pleasure", showing that in antiquity the liver was considered to be the seat
      of soul and human feelings. In Romance languages, the Latin term "ficatum" was
      linked to the ancient practice of fattening geese with figs (ficus in Latin) to
      make their livers more delicious. This relationship between the liver, fat, and
      carbohydrates seems to indicate that ancient gourmets had clear knowledge of the
      nutritional mechanisms underlying "fatty liver" in animals. On the other hand,
      the Germanic term "lifere" was initially connected to "life", underscoring the
      relation of the liver to health and existence. In the Early Modern Age, the liver
      became a recurring image in political reflection, especially within the
      Elizabethan tradition of the body politic, where the king was frequently
      described as the "liver" of his country. Finally, the liver was used to indicate
      courage, or the lack of it: some modern French and English idiomatic expressions
      derive from the ancient belief that people who had no blood in their liver ("lily
      livered") would thus be cowards or betrayers.

PMID- 21718667
TI  - Hepatitis B surface antigen quantification: why and how to use it in 2011 - a
      core group report.
AB  - Quantitative HBsAg had been suggested to be helpful in management of HBV, but
      assays were cumbersome. The recent availability of commercial quantitative assays
      has restarted the interest in quantitative serum hepatitis B surface antigen
      (HBsAg) as a biomarker for prognosis and treatment response in chronic hepatitis
      B. HBsAg level reflects the transcriptional activity of cccDNA rather than the
      absolute amount of cccDNA copies. Serum HBsAg level tends to be higher in
      hepatitis B e antigen (HBeAg)-positive than HBeAg-negative patients. Among
      patients with a low HBV DNA (<2000IU/ml), HBsAg <1000IU/ml in genotype D HBV
      infection and HBsAg <100IU/ml in genotype B/C HBV infection is associated with
      inactive carrier state in HBeAg-negative patients. The HBsAg reduction by
      nucleos(t)ide analogues (NA) is not as pronounced as by interferon treatment. On
      peginterferon treatment, sustained responders tend to show greater HBsAg decline
      than the non-responders. The optimal on-treatment HBsAg cutoff to predict
      response needs further evaluation in HBeAg-positive patients, but an absence of
      HBsAg decline together with a <2 log reduction in HBV DNA at week 12 can serve as
      stopping rule in HBeAg-negative patients with genotype D HBV infection. A rapid
      serum HBsAg decline during NA therapy may identify patients who will clear HBsAg
      in the long-term. There are early reports among Asian patients that an HBsAg
      level of <100IU/ml might predict lower risk of relapse after stopping NA
      treatment. In clinical practice, serum HBsAg level should be used together with,
      but not as a substitute for, HBV DNA.

PMID- 21718668
TI  - Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or
      fiction?
AB  - Patients with cirrhosis can have abnormalities in laboratory tests reflecting
      changes in primary haemostasis, including bleeding time, platelet function tests,
      markers of platelet activation, and platelet count. Such changes have been
      considered particularly relevant in the bleeding complications that occur in
      cirrhosis. However, several studies have shown that routine diagnostic tests,
      such as platelet count, bleeding time, PFA-100, thromboelastography are not
      clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover,
      treatments used to increase platelet count or to modulate platelet function could
      potentially do harm. Consequently the optimal management of bleeding
      complications is still a matter of discussion. Moreover, in the last two decades
      there has been an increased recognition that not only bleeding but also
      thrombosis complicates the clinical course of cirrhosis. Thus, we performed a
      literature search looking at publications studying both qualitative and
      quantitative aspects of platelet function to verify which primary haemostasis
      defects occur in cirrhosis. In addition, we evaluated the contribution of
      qualitative and quantitative aspects of platelet function to the clinical outcome
      in cirrhosis and their therapeutic management according to the data available in
      the literature. From the detailed analysis of the literature, it appears clear
      that primary haemostasis may not be defective in cirrhosis, and a low platelet
      count should not necessarily be considered as an automatic index of an increased
      risk of bleeding. Conversely, caution should be observed in patients with severe
      thrombocytopenia where its correction is advised if bleeding occurs and before
      invasive diagnostic and therapeutic procedures.

PMID- 21718669
TI  - The critical role of medication adherence in the success of boceprevir and
      telaprevir in clinical practice.

PMID- 21718670
TI  - HBV treatment and pregnancy.

PMID- 21718671
TI  - Pitavastatin enhances antiviral efficacy of standard pegylated interferon plus
      ribavirin in patients with chronic hepatitis C: a prospective randomized pilot
      study.

PMID- 21718672
TI  - Criteria for liver transplantation for HCC: what should the limits be?
AB  - Liver transplantation is a well-established treatment in a subset of patients
      with cirrhosis and hepatocellular carcinoma. The Milan criteria (single nodule up
      to 5 cm, up to three nodules none larger than 3 cm, with no evidence of
      extrahepatic spread or macrovascular invasion) have been traditionally accepted
      as standard of care. However, some groups have proposed that these criteria are
      too restrictive, and exclude some patients from transplantation who might benefit
      from this procedure. Transplanting patients with tumors beyond the established
      criteria falls into two categories, those whose tumors are beyond the Milan
      criteria at presentation without the use of treatment prior to transplantation
      (expanded criteria), and those in whom treatment allows the Milan Criteria to be
      fulfilled (down-staging). Currently, however, there is no international consensus
      regarding these approaches in clinical practice. The purpose of this systematic
      review is to clarify this debate through a critical analysis of available data.
      Finally, some comments on predictive factors apart from morphological
      characteristics are also addressed.

PMID- 21718674
TI  - Antibacterial activity, inflammatory response, coagulation and cytotoxicity
      effects of silver nanoparticles.
AB  - The incorporation of nanoparticles (NPs) in industrial and biomedical
      applications has increased significantly in recent years, yet their hazardous and
      toxic effects have not been studied extensively. Here, we studied the effects of
      24 nm silver NPs (AgNPs) on a panel of bacteria isolated from medical devices
      used in a hospital intensive care unit. The cytotoxic effects were evaluated in
      macrophages and the expression of the inflammatory cytokines IL-6, IL-10 and TNF
      alpha were quantified. The effects of NPs on coagulation were tested in vitro in
      plasma-based assays. We demonstrated that 24 nm AgNPs were effective in
      suppressing the growth of clinically relevant bacteria with moderate to high
      levels of antibiotic resistance. The NPs had a moderate inhibitory effect when
      coagulation was initiated through the intrinsic pathway. However, these NPs are
      cytotoxic to macrophages and are able to elicit an inflammatory response. Thus,
      beneficial and potential harmful effects of 24 nm AgNPs on biomedical devices
      must be weighed in further studies in vivo. From the Clinical Editor: The authors
      of this study demonstrate that gallic acid reduced 24 nm Ag NPs are effective in
      suppressing growth of clinically relevant antibiotic resistant bacteria. However,
      these NPs also exhibit cytotoxic properties to macrophages and may trigger an
      inflammatory response. Thus, the balance of beneficial and potential harmful
      effects must be weighed carefully in further studies.

PMID- 21718675
TI  - Sequence analysis of the spliced-leader intergenic region (SL-IR) and random
      amplified polymorphic DNA (RAPD) of Trypanosoma rangeli strains isolated from
      Rhodnius ecuadoriensis, R. colombiensis, R. pallescens and R. prolixus suggests a
      degree of co-evolution between parasites and vectors.
AB  - Spliced leader intergenic region (SL-IR) sequences from 23 Trypanosoma rangeli
      strains isolated from the salivary glands of Rhodnius colombiensis, R.
      ecuadoriensis, R. pallescens and R. prolixus and two human strains revealed the
      existence of 4 genotypes with CA, GT, TA, ATT and GTAT microsatellite repeats and
      the presence of insertions/deletions (INDEL) and single nucleotide polymorphism
      (SNP) characterizing each genotype. The strains isolated from the same vector
      species or the same Rhodnius evolutionary line presented the same genotypes, even
      in cases where strains had been isolated from vectors captured in geographically
      distant regions. The dendrogram constructed from the SL-IR sequences separated
      all of them into two main groups, one with the genotypes isolated from R.
      prolixus and the other group containing three well defined sub-groups with the
      genotypes isolated from R. pallescens, R. colombiensis and R. ecuadoriensis.
      Random amplified polymorphic DNA (RAPD) analysis showed the same two main groups
      and sub-groups supporting strict T. rangeli genotypes' association with Rhodnius
      species. Combined with other studies, these results suggest a possible co
      evolutionary association between T. rangeli genotypes and their vectors.

PMID- 21718676
TI  - Inhibiting angiotensin-converting enzyme promotes renal repair by limiting
      progenitor cell proliferation and restoring the glomerular architecture.
AB  - We previously reported that angiotensin-converting enzyme inhibitor (ACEi)
      renoprotection in Munich Wistar Fromter (MWF) rats, which develop progressive
      glomerular injury, was associated with podocyte repopulation and preservation of
      glomerular architecture. Here, we studied the time course of the lesions, their
      cellular components, and the effect of ACEi. Early glomerular lesions were
      synechiae, followed by extracapillary crescents and glomerulosclerosis. The
      majority of cells forming crescents were claudin1(+) parietal epithelial cells
      and, to a lesser extent, WT1(+) podocytes, both in active proliferation. In
      crescents, cells expressing the metanephric mesenchyme marker NCAM were also
      found. Three distinct populations of parietal epithelial cells were identified in
      the rat Bowman's capsule: NCAM(+)WT1(-) cells, also expressing progenitor cell
      marker CD24, and NCAM(+)WT1(+) and NCAM(-)WT1(+) cells, the latter population
      representing parietal podocytes. After exposure to inductive medium, cultured
      parietal epithelial cells that were obtained by capsulated glomeruli generated
      podocytes, documenting their progenitor nature. Mitotic activity of cultured
      renal progenitors was induced by angiotensin II through the down-regulation of
      cell cycle inhibitor C/EBPdelta expression. Treatment with ACEi reduced number
      and extension of crescents and glomerulosclerosis in MWF rats. Renoprotection was
      accomplished through the limitation of NCAM(+) progenitor proliferation via the
      modulation of C/EBPdelta. Thus, chaotic migration and proliferation of the
      Bowman's capsule progenitor cells pave the way to crescent formation and
      subsequent sclerosis. ACEi, by moderating progenitor cell activation, restores
      glomerular architecture and prevents renal disease progression.

PMID- 21718677
TI  - The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in
      mice.
AB  - Deep infiltrating endometriosis (DIE) is a particular clinical and histological
      entity of endometriosis responsible for chronic pelvic pain and infertility. Here
      we characterize the proliferative phenotype of DIE cells, to explore the cellular
      and molecular mechanisms that could explain their aggressive potential. In
      addition, the inhibition of mTOR/AKT pathway was tested, as a potential treatment
      of DIE. Included were 22 patients with DIE and 12 control patients without
      endometriosis. Epithelial and stromal cells were extracted from biopsies of
      eutopic endometrium and deep infiltrating endometriotic nodules from patients
      with DIE. Cell proliferation was determined by thymidine incorporation. Oxidative
      stress was assayed by spectrofluorometry. The ERK and mTOR/AKT pathways were
      analyzed in vitro by Western blot and for AKT in vivo in a mouse model of DIE.
      The proliferation rate of eutopic endometrial cells and of deep infiltrating
      endometriotic cells from DIE patients was higher than that of endometrial cells
      from controls. The hyperproliferative phenotype of endometriotic cells was
      associated with an increase in endogenous oxidative stress, and with activation
      of the ERK and mTOR/AKT pathways. mTOR/AKT inhibition by temsirolimus decreased
      endometriotic cell proliferation both in vitro and in vivo in a mouse model of
      DIE. Blocking the mTOR/AKT pathway offers new prospects for the treatment of DIE.

PMID- 21718678
TI  - Differential roles of endothelin-1 in angiotensin II-induced atherosclerosis and
      aortic aneurysms in apolipoprotein E-null mice.
AB  - Because both endothelin-1 (ET-1) and angiotensin II (AngII) are independent
      mediators of arterial remodeling, we sought to determine the role of ET receptor
      inhibition in AngII-accelerated atherosclerosis and aortic aneurysm formation. We
      administered saline or AngII and/or bosentan, an endothelin receptor antagonist
      (ERA) for 7, 14, or 28 days to 6-week- and 6-month-old apolipoprotein E-knockout
      mice. AngII treatment increased aortic atherosclerosis, which was reduced by ERA.
      ET-1 immunostaining was localized to macrophage-rich regions in aneurysmal
      vessels. ERA did not prevent AngII-induced aneurysm formation but instead may
      have increased aneurysm incidence. In AngII-treated animals with aneurysms, ERA
      had a profound effect on the non-aneurysmal thoracic aorta via increasing wall
      thickness, collagen/elastin ratio, wall stiffness, and viscous responses. These
      observations were confirmed in acute in vitro collagen sheet production models in
      which ERA inhibited AngII's dose-dependent effect on collagen type 1 alpha 1
      (COL1A1) gene transcription. However, chronic treatment reduced matrix
      metalloproteinase 2 mRNA expression but enhanced COL3A1, tissue inhibitor of
      metalloproteinase 1 (TIMP-1), and TIMP-2 mRNA expressions. These data confirm a
      role for the ET system in AngII-accelerated atherosclerosis but suggest that ERA
      therapy is not protective against the formation of AngII-induced aneurysms and
      can paradoxically stimulate a chronic arterial matrix remodeling response.

PMID- 21718679
TI  - The pathogenic role of cystathionine gamma-lyase/hydrogen sulfide in
      streptozotocin-induced diabetes in mice.
AB  - Reduced beta-cell mass and increased activities of ATP-sensitive K(+) channels in
      pancreatic beta cells are associated with the pathogenesis of diabetes.
      Cystathionine gamma-lyase (CSE) is a major hydrogen sulfide (H(2)S)-producing
      enzyme in pancreatic beta cells. Herein, we examine the effects of genetic and
      pharmacologic ablation of CSE on beta-cell functions and their correlation with
      streptozotocin (STZ)-induced diabetes. Compared with wild-type mice, CSE knockout
      (CSE KO) mice that received STZ injections exhibited a delayed onset of diabetic
      status. The application of dl-propargylglycine (PPG) to inhibit CSE activity
      protected wild-type mice from STZ-induced hyperglycemia and hypoinsulinemia. STZ
      significantly increased pancreatic H(2)S production in wild-type mice but not in
      CSE KO mice. STZ induced more apoptotic beta-cell death in wild-type mice than in
      CSE KO mice. STZ exposure decreased the viability of cultured INS-1E cells, which
      was partly reversed by PPG co-treatment. STZ also significantly stimulated H(2)S
      production in cultured INS-1E cells. In addition, STZ stimulated ATP-sensitive
      K(+) currents in pancreatic beta cells from wild-type mice but not in the
      presence of PPG or in beta cells from CSE KO mice. Sodium hydrosulfide injection
      instantly increased blood glucose, decreased plasma insulin, and deteriorated
      glucose tolerance in mice. Take together, these results provide evidence that the
      CSE/H(2)S system plays a critical role in regulating beta-cell functions.

PMID- 21718680
TI  - Inhibition of Fas ligand in NOD mice unmasks a protective role for IL-10 against
      insulitis development.
AB  - Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the destruction
      of pancreatic insulin-producing beta cells by autoreactive T cells early in life.
      Despite daily insulin injections, patients typically develop cardiovascular and
      other complications; and intensive efforts are being directed toward identifying
      therapeutic targets to prevent the disease without directly impinging on the host
      defense. Fas ligand (FasL) is one potential target. Fas-FasL interactions
      primarily regulate T-cell homeostasis, not activation. Nevertheless, spontaneous
      gene mutation of Fas (called lpr mutation) or FasL (called the gld mutation)
      prevents autoimmune diabetes in nonobese diabetic (NOD) mice, the widely used
      model for T1D. Furthermore, although homozygous gld mutations cause age-dependent
      lymphoproliferation, limiting the gld mutation to one allele (NOD-gld/+) or
      treating NOD-wild-type mice with FasL-neutralizing monoclonal antibody completely
      prevents the disease development without causing lymphoproliferation or immune
      suppression. Herein, we show that the heterozygous gld mutation inhibits the
      accumulation of diabetogenic T cells in the pancreas, without interfering with
      their proliferation and expansion in the draining pancreatic lymph nodes.
      Pancreata from NOD-gld/+ mice contained B cells that expressed CD5 and produced
      IL-10, which was critical for maintenance of the disease resistance because its
      neutralization with an IL-10 receptor-blocking monoclonal antibody allowed
      accumulation of CD4 T cells in the pancreas and led to insulitis development. The
      results provide novel insights into the pathogenesis of T1D that could have
      important therapeutic implications.

PMID- 21718681
TI  - Survivin is a novel target of CD44-promoted breast tumor invasion.
AB  - The hyaluronan (HA) receptor CD44 plays an essential role in cell-cell or cell
      extracellular matrix communications and is a bioactive signal transmitter.
      Although a number of studies have described the function of CD44 in breast cancer
      (BC) metastasis, the underlying mechanisms have yet to be determined. By using a
      validated tetracycline-off-regulated CD44 expression system in the MCF-7 cell
      line combined with microarray analysis, we identified survivin (SVV) as a
      potential downstream transcriptional target of CD44. To test the hypothesis that
      SVV underpins CD44-promoted BC cell invasion, we combined molecular and
      pharmacologic approaches and showed that CD44 induction increased SVV expression
      levels, which in turn promotes BC cell invasion. Further, clinical analysis of
      breast tissue samples showed that SVV expression patterns paralleled those of the
      standard form of CD44 during breast tumor progression. More interestingly, we
      identified the PI3K/E2F1 pathway as a potential molecular link between HA/CD44
      activation and SVV transcription. In addition to identifying SVV as a target for
      HA/CD44 signaling, this investigation provides a better understanding of the
      molecular mechanisms that underpin the novel function of SVV in breast cancer
      metastasis.

PMID- 21718682
TI  - Pathogenic relevance of IgG and IgM antibodies against desmoglein 3 in blister
      formation in pemphigus vulgaris.
AB  - Pemphigus vulgaris is an autoimmune disease caused by IgG antibodies against
      desmoglein 3 (Dsg3). Previously, we isolated a pathogenic mAb against Dsg3, AK23
      IgG, which induces a pemphigus vulgaris-like phenotype characterized by blister
      formation. In the present study, we generated a transgenic mouse expressing AK23
      IgM to examine B-cell tolerance and the pathogenic role of IgM. Autoreactive
      transgenic B cells were found in the spleen and lymph nodes, whereas anti-Dsg3
      AK23 IgM was detected in the cardiovascular circulation. The transgenic mice did
      not develop an obvious pemphigus vulgaris phenotype, however, even though an
      excess of AK23 IgM was passively transferred to neonatal mice. Similarly, when
      hybridoma cells producing AK23 IgM were inoculated into adult mice, no blistering
      was observed. Immunoelectron microscopy revealed IgM binding at the edges of
      desmosomes or interdesmosomal cell membranes, but not in the desmosome core,
      where AK23 IgG binding has been frequently detected. Furthermore, in an in vitro
      dissociation assay using cultured keratinocytes, AK23 IgG and AK23 IgM F(ab')(2)
      fragments, but not AK23 IgM, induced fragmentation of epidermal sheets. Together,
      these observations indicate that antibodies must gain access to Dsg3 integrated
      within desmosomes to induce the loss of keratinocyte cell-cell adhesion. These
      findings provide an important framework for improved understanding of B-cell
      tolerance and the pathophysiology of blister formation in pemphigus.

PMID- 21718683
TI  - Herbicide effect on the photodamage process of photosystem II: fourier transform
      infrared study.
AB  - The photodamage process of photosystem II by strong illumination was investigated
      by examining the herbicide effects on the photoinactivation of redox cofactors.
      O(2)-evolving photosystem II membranes from spinach in the absence of herbicide
      and in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and
      bromoxynil were subjected to strong white-light illumination at 298K, and the
      illumination-time dependence of the activities of Q(A), the Mn cluster, and P680
      were monitored using light-induced Fourier transform infrared (FTIR) difference
      spectroscopy. The decrease in the Q(A) activity was suppressed and accelerated by
      DCMU and bromoxynil, respectively, in comparison with the sample without
      herbicide. The intensity change in the S(2)/S(1) FTIR signal of the Mn cluster
      exhibited a time course virtually identical to that in the Q(A) signal in all the
      three samples, suggesting that the loss of the S(1)->S(2) transition was ascribed
      to the Q(A) inactivation and hence the Mn cluster was inactivated not faster than
      Q(A). The decrease in the P680 signal was always slower than that of Q(A) keeping
      the tendency of the herbicide effect. Degradation of the D1 protein occurred
      after the P680 inactivation. These observations are consistent with the acceptor
      side mechanism, in which double reduction of Q(A) triggers the formation of
      (1)O(2)* to promote further damage to other cofactors and the D1 protein, rather
      than the recently proposed mechanism that inactivation of the Mn cluster
      initiates the photodamage. Thus, the results of the present study support the
      view that the acceptor-side mechanism dominantly occurs in the photodamage to
      PSII by strong white-light illumination.

PMID- 21718684
TI  - The O(2) reduction and proton pumping gate mechanism of bovine heart cytochrome c
      oxidase.
AB  - X-ray structures of bovine heart cytochrome c oxidase with bound respiratory
      inhibitors (O(2) analogues) have been determined at 1.8-2.05A resolution to
      investigate the function of the O(2) reduction site which includes two metal
      sites (Fe(a3)(2+) and Cu(B)(1+)). The X-ray structures of the CO- and NO-bound
      derivatives indicate that although there are three possible electron donors that
      can provide electrons to the bound O(2), located in the O(2) reduction site, the
      formation of the peroxide intermediate is effectively prevented to provide an
      O(2)-bound form as the initial intermediate. The structural change induced upon
      binding of CN(-) suggests a non-sequential 3-electron reduction of the bound
      O(2)(-) for the complete reduction without release of any reactive oxygen
      species. The X-ray structure of the derivative with CO bound to Cu(B)(1+) after
      photolysis from Fe(a3)(2+) demonstrates weak side-on binding. This suggests that
      Cu(B) controls the O(2) supply to Fe(a3)(2+) without electron transfer to provide
      sufficient time for collection of protons from the negative side of the
      mitochondrial membrane. The proton-pumping pathway of bovine heart cytochrome c
      oxidase includes a hydrogen-bond network and a water channel located in tandem
      between the positive and negative side of the mitochondrial membrane. Binding of
      a strong ligand to Fe(a3) induces a conformational change which significantly
      narrows the water channel and effectively blocks the back-leakage of protons from
      the hydrogen bond network. The proton pumping mechanism proposed by these X-ray
      structural analyses has been functionally confirmed by mutagenesis analyses of
      bovine heart cytochrome c oxidase. This article is part of a Special Issue
      entitled: Allosteric cooperativity in respiratory proteins.

PMID- 21718685
TI  - Light-induced isomerization of the LHCII-bound xanthophyll neoxanthin: possible
      implications for photoprotection in plants.
AB  - Light-harvesting pigment-protein complex of Photosystem II (LHCII) is the largest
      photosynthetic antenna complex of plants and the most abundant membrane protein
      in the biosphere. Plant fitness and productivity depend directly on a balance
      between excitations in the photosynthetic apparatus, generated by captured light
      quanta, and the rate of photochemical processes. Excess excitation energy leads
      to oxidative damage of the photosynthetic apparatus and entire organism and
      therefore the balance between the excitation density and photosynthesis requires
      precise and efficient regulation, operating also at the level of antenna
      complexes. We show that illumination of the isolated LHCII leads to isomerization
      of the protein-bound neoxanthin from conformation 9'-cis to 9',13- and 9',13'
      dicis forms. At the same time light-driven excitation quenching is observed,
      manifested by a decrease in chlorophyll a fluorescence intensity and shortened
      fluorescence lifetimes. Both processes, the neoxanthin isomerization and the
      chlorophyll excitation quenching, are reversible in dim light. The results of the
      77K florescence measurements of LHCII show that illumination is associated with
      appearance of the low-energy states, which can serve as energy traps in the
      pigment-protein complex subjected to excess excitation. Possible sequence of the
      molecular events is proposed, leading to a protective excess excitation energy
      quenching: neoxanthin photo-isomerization->formation of LHCII supramolecular
      structures which potentiate creation of energy traps->excitation quenching.

PMID- 21718686
TI  - Radical formation in cytochrome c oxidase.
AB  - The formation of radicals in bovine cytochrome c oxidase (bCcO), during the O(2)
      redox chemistry and proton translocation, is an unresolved controversial issue.
      To determine if radicals are formed in the catalytic reaction of bCcO under
      single turnover conditions, the reaction of O(2) with the enzyme, reduced by
      either ascorbate or dithionite, was initiated in a custom-built rapid freeze
      quenching (RFQ) device and the products were trapped at 77K at reaction times
      ranging from 50MUs to 6ms. Additional samples were hand mixed to attain multiple
      turnover conditions and quenched with a reaction time of minutes. X-band (9GHz)
      continuous wave electron paramagnetic resonance (CW-EPR) spectra of the reaction
      products revealed the formation of a narrow radical with both reductants. D-band
      (130GHz) pulsed EPR spectra allowed for the determination of the g-tensor
      principal values and revealed that when ascorbate was used as the reductant the
      dominant radical species was localized on the ascorbyl moiety, and when
      dithionite was used as the reductant the radical was the SO(2)(-) ion. When the
      contributions from the reductants are subtracted from the spectra, no evidence
      for a protein-based radical could be found in the reaction of O(2) with reduced
      bCcO. As a surrogate for radicals formed on reaction intermediates, the reaction
      of hydrogen peroxide (H(2)O(2)) with oxidized bCcO was studied at pH 6 and pH 8
      by trapping the products at 50MUs with the RFQ device to determine the initial
      reaction events. For comparison, radicals formed after several minutes of
      incubation were also examined, and X-band and D-band analysis led to the
      identification of radicals on Tyr-244 and Tyr-129. In the RFQ measurements, a
      peroxyl (ROO) species was formed, presumably by the reaction between O(2) and an
      amino acid-based radical. It is postulated that Tyr-129 may play a central role
      as a proton loading site during proton translocation by ejecting a proton upon
      formation of the radical species and then becoming reprotonated during its
      reduction via a chain of three water molecules originating from the region of the
      propionate groups of heme a(3). This article is part of a Special Issue entitled:
      "Allosteric cooperativity in respiratory proteins".

PMID- 21718687
TI  - Non-channel functions of connexins in cell growth and cell death.
AB  - Cellular communication mediated by gap junction channels and hemichannels, both
      composed of connexin proteins, constitutes two acknowledged regulatory platforms
      in the accomplishment of tissue homeostasis. In recent years, an abundance of
      reports has been published indicating functions for connexin proteins in the
      control of the cellular life cycle that occur independently of their channel
      activities. This has yet been most exemplified in the context of cell growth and
      cell death, and is therefore as such addressed in the current paper. Specific
      attention is hereby paid to the molecular mechanisms that underpin the cellular
      non-channel roles of connexin proteins, namely the alteration of the expression
      of tissue homeostasis determinants and the physical interaction with cell growth
      and cell death regulators. This article is part of a Special Issue entitled: The
      Communicating junctions, composition, structure and characteristics.

PMID- 21718688
TI  - Cationic amphipathic peptides accumulate sialylated proteins and lipids in the
      plasma membrane of eukaryotic host cells.
AB  - Cationic antimicrobial peptides (CAMPs) selectively target bacterial membranes by
      electrostatic interactions with negatively charged lipids. It turned out that for
      inhibition of microbial growth a high CAMP membrane concentration is required,
      which can be realized by the incorporation of hydrophobic groups within the
      peptide. Increasing hydrophobicity, however, reduces the CAMP selectivity for
      bacterial over eukaryotic host membranes, thereby causing the risk of detrimental
      side-effects. In this study we addressed how cationic amphipathic peptides-in
      particular a CAMP with Lysine-Leucine-Lysine repeats (termed KLK)-affect the
      localization and dynamics of molecules in eukaryotic membranes. We found KLK to
      selectively inhibit the endocytosis of a subgroup of membrane proteins and lipids
      by electrostatically interacting with negatively charged sialic acid moieties.
      Ultrastructural characterization revealed the formation of membrane invaginations
      representing fission or fusion intermediates, in which the sialylated proteins
      and lipids were immobilized. Experiments on structurally different cationic
      amphipathic peptides (KLK, 6-MO-LF11-322 and NK14-2) indicated a cooperation of
      electrostatic and hydrophobic forces that selectively arrest sialylated membrane
      constituents.

PMID- 21718689
TI  - Regulation of cysteine-rich protein 2 localization by the development of actin
      fibers during smooth muscle cell differentiation.
AB  - Cysteine-rich protein 2 (CRP2) is a cofactor for smooth muscle cell (SMC)
      differentiation. Here, we examined the mechanism of CRP2 distribution dynamics
      during SMC differentiation. CRP2 protein directly associated with F-actin through
      its N-terminal LIM domain and Gly-rich region, as determined by ELISA. In
      undifferentiated cells that contain few actin stress fibers, CRP2 was broadly
      distributed throughout the whole cell, including the nucleus. After induction of
      SMC differentiation, CRP2 localized to actin stress fibers as they formed. The
      stress fiber-localized CRP2 entered the nucleus because of induced actin
      depolymerization. These CRP2 dynamics were reproduced by in silico simulation.
      CRP2 localization dynamics, which affect CRP2 function, are regulated by the
      formation of actin stress fibers in conjunction with SMC differentiation.

PMID- 21718690
TI  - The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a
      dominant negative regulator of alpha7*nAChR function.
AB  - The human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a
      candidate gene for schizophrenia and an important drug target for cognitive
      deficits in the disorder. Activation of the alpha7*nAChR, results in opening of
      the channel and entry of mono- and divalent cations, including Ca(2+), that
      presynaptically participates to neurotransmitter release and postsynaptically to
      down-stream changes in gene expression. Schizophrenic patients have low levels of
      alpha7*nAChR, as measured by binding of the ligand [(125)I]-alpha-bungarotoxin (I
      BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was
      partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the
      human brain and elsewhere in the body. The association between a 2bp deletion in
      CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to
      cognitive impairment. To examine the putative contribution of CHRFAM7A on
      receptor function, co-expression of alpha7 and the duplicate genes was carried
      out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded
      protein expression but no functional receptor and co-expression with alpha7
      caused a significant reduction of the amplitude of the ACh-evoked currents.
      Reduced current amplitude was not correlated with a reduction of I-BTX binding,
      suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis
      is supported by a larger increase of the ACh-evoked current by the allosteric
      modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU
      120596) in cells expressing the duplicate than in the control. These results
      suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function
      and is critical for receptor regulation in humans.

PMID- 21718691
TI  - Functionally biased modulation of A(3) adenosine receptor agonist efficacy and
      potency by imidazoquinolinamine allosteric enhancers.
AB  - Allosteric modulators for the G(i)-coupled A(3) adenosine receptor (AR) are of
      considerable interest as therapeutic agents and as pharmacological tools to probe
      various signaling pathways. In this study, we initially characterized the effects
      of several imidazoquinolinamine allosteric modulators (LUF5999, LUF6000 and
      LUF6001) on the human A(3) AR stably expressed in CHO cells using a cyclic AMP
      functional assay. These modulators were found to affect efficacy and potency of
      the agonist Cl-IB-MECA differently. LUF5999 (2-cyclobutyl derivative) enhanced
      efficacy but decreased potency. LUF6000 (2-cyclohexyl derivative) enhanced
      efficacy without affecting potency. LUF6001 (2-H derivative) decreased both
      efficacy and potency. We further compared the agonist enhancing effects of
      LUF6000 in several other A(3) AR-mediated events. It was shown that although
      LUF6000 behaved somewhat differently in various signaling pathways, it was more
      effective in enhancing the effects of low-efficacy than of high-efficacy
      agonists. In an assay of cyclic AMP accumulation, LUF6000 enhanced the efficacy
      of all agonists examined, but in the membrane hyperpolarization assay, it only
      enhanced the efficacy of partial agonists. In calcium mobilization, LUF6000 did
      not affect the efficacy of the full agonist NECA but was able to switch the
      nucleoside antagonist MRS542 into a partial agonist. In translocation of beta
      arrestin2, the agonist-enhancing effect LUF6000 was not pronounced. In an assay
      of ERK1/2 phosphorylation LUF6000 did not show any effect on the efficacy of Cl
      IB-MECA. The differential effects of LUF6000 on the efficacy and potency of the
      agonist Cl-IB-MECA in various signaling pathway were interpreted quantitatively
      using a mathematical model.

PMID- 21718692
TI  - Association of sVAP-1, sRAGE, and CML with lactation-induced insulin sensitivity
      in young non-diabetic healthy women.
AB  - BACKGROUND: In comparison with non-lactating women breast-feeding mothers display
      higher insulin sensitivity. Recent data suggest that advanced glycation end
      products, soluble receptor for advanced glycation end products (sRAGE) and
      soluble vascular adhesion protein-1 (sVAP-1) may play a role in insulin
      resistance even in healthy subjects. AIM: We studied whether breast-feeding
      induced insulin sensitivity associates with changes in concentrations of
      circulating sVAP-1, sRAGE and N(epsilon)-(carboxymethyl)lysine (CML) - chemically
      defined advanced glycation end product and RAGE ligand. METHODS: In 74 lactating
      non-diabetic mothers, 45 weaned non-diabetic mothers and 50 age-matched non
      parous women insulin sensitivity was assessed using Quantitative insulin
      sensitivity check index (QUICKI). sVAP-1, sRAGE and CML levels were determined.
      RESULTS: Lactating mothers were more insulin sensitive than their weaned and non
      parous counterparts. Lactating mothers displayed the highest concentrations of
      sRAGE, and higher sVAP-1 levels if compared to weaned mothers. Both groups of
      mothers presented with lower CML levels than the non-parous women. CONCLUSION:
      Lactation-induced insulin sensitivity is associated with higher sVAP-1 and a
      tendency towards higher sRAGE levels. Lactation-associated rise in sVAP-1 may
      promote effective glucose utilization in the mother. Lactation-induced insulin
      sensitivity vanishes shortly after weaning. In young healthy women CML levels are
      of no clinical relevance to insulin sensitivity.

PMID- 21718693
TI  - Inhibitory Smads differentially regulate cell fate specification and axon
      dynamics in the dorsal spinal cord.
AB  - The roof plate resident BMPs have sequential functions in the developing spinal
      cord, establishing cell fate and orienting axonal trajectories. These activities
      are, however, restricted to the dI1-dI3 neurons in the most dorsal region of the
      spinal cord. What limits the extent of the action of the BMPs to these neurons?
      To address this question, we have examined both the distribution of the
      inhibitory Smads (I-Smads), Smad6 and Smad7 in the spinal cord and the
      consequence of ectopically expressing the I-Smads in chicken embryos. Our studies
      suggest that the I-Smads function in vivo to restrict the action of BMP signaling
      in the dorsal spinal cord. Moreover, the I-Smads have distinct roles in
      regulating the diverse activities of the BMPs. Thus, the ectopic expression of
      Smad7 suppresses the dI1 and dI3 neural fates and concomitantly increases the
      number of dI4-dI6 spinal neurons. In contrast, Smad6 most potently functions to
      block dI1 axon outgrowth. Taken together, these experiments suggest that the I
      Smads have distinct roles in spatially limiting the response of cells to BMP
      signaling.

PMID- 21718694
TI  - The tailless ortholog nhr-67 functions in the development of the C. elegans
      ventral uterus.
AB  - The development of the C. elegans uterus provides a model for understanding the
      regulatory pathways that control organogenesis. In C. elegans, the ventral uterus
      develops through coordinated signaling between the uterine anchor cell (AC) and a
      ventral uterine (VU) cell. The nhr-67 gene encodes the nematode ortholog of the
      tailless nuclear receptor gene. Fly and vertebrate tailless genes function in
      neuronal and ectodermal developmental pathways. We show that nhr-67 functions in
      multiple steps in the development of the C. elegans uterus. First, it functions
      in the differentiation of the AC. Second, it functions in reciprocal signaling
      between the AC and an equipotent VU cell. Third, it is required for a later
      signaling event between the AC and VU descendants. nhr-67 is required for the
      expression of both the lag-2/Delta signal in the AC and the lin-12/Notch receptor
      in all three VU cells and their descendants, suggesting that nhr-67 may be a key
      regulator of Notch-signaling components. We discuss the implications of these
      findings for proposed developmental regulatory pathways that include the helix
      loop-helix regulator hlh-2/daughterless and transcription factor egl-43/Evi1 in
      the differentiation of ventral uterine cell types.

PMID- 21718695
TI  - An in vitro model for testing drugs to treat tinnitus.
AB  - Tinnitus affects approximately 50 million people in the USA alone, with 10
      million being highly debilitated. Pharmacotherapy for tinnitus is still in
      emerging stages due to time consuming clinical trials and/or animal experiments.
      We tested a new cellular model where induced rapid neuronal firing or spiking was
      used as a mimic for the type of aberrant activity that may occur in tinnitus.
      Spontaneously active auditory cortical networks growing on microelectrode arrays
      were exposed to pentylenetetrazol (PTZ), a proconvulsant and an antagonist of
      GABA(A) receptor, which is implicated in tinnitus. Auditory cortical networks
      were then exposed to experimental tinnitus drugs linopirdine (Dup966, a potassium
      channel blocker), L-carnitine (an antioxidant), or selective Ca(2+) channel
      antagonists pregabalin (Lyrica), or gabapentin (Neurontin) at various
      concentrations. PTZ increased spike rate by 139.6+/-27% and burst rate by 129.7+/
      28% in auditory cortical networks with a phenotypic high firing of excitable
      neurons. Reductions of increased activity were observed to varying degrees using
      the experimental tinnitus drugs. The potency of the drugs was linopirdine
      (EC(50): 176+/-7.0 MUM)>L-carnitine (EC(50): 1569+/-41 MUM)>pregabalin (EC(50):
      8360+/-340 MUM), >gabapentin, with 34.2+/-7.5% efficacy (EC(50): 2092+/-980 MUM).
      These studies provide proof of principle for the use of auditory cortical
      networks on microelectrode array as a feasible platform for semi-high throughput
      application for screening of drugs that might be used for the treatment of
      tinnitus.

PMID- 21718696
TI  - Effects of free fatty acids on meibomian lipid films.
AB  - The purpose of this study was to evaluate the impact of free fatty acids (FFA),
      namely oleic (OA) and linoleic (LA) ones, on meibomian lipid films (MLF) using a
      Langmuir trough (LT) and a Brewster angle microscope (BAM). Human meibum was
      collected from healthy volunteers. A Tris-buffered saline (TBS, pH 7.4) was used
      as the control aqueous subphase for LT experiments. Then, varying amounts of OA
      and LA were dissolved in TBS to make FFA-containing subphases. Predetermined
      amounts of meibum were loaded onto the surface of the (TBS/+/-FFA) subphases to
      form MLF. Then, surface pressure-area (pi/A) isotherms of MLF were recorded.
      Standard rheological parameters such as rigidity, elasticity, and hysteresis,
      were computed. In a separate experiment, OA and LA were pre-mixed with meibum at
      different weight ratios prior their spreading onto the control TBS subphase, and
      the (pi/A) isotherms of the resulting mixed films of meibum and FFA were studied
      and analyzed in the same fashion as described above. When studied at the normal
      corneal temperature of 34  degrees C with the (TBS/-FFA) subphase, meibum formed
      stable films. When (TBS/+FFA) subphase was used, both FFA quickly disrupted the
      MLF, acting in a similar fashion. BAM revealed that the most dramatic changes in
      the structure of MLF occurred in the range of OA concentrations between 5 and 15
      MUM. However, this effect was apparent even with 2.5 MUM OA. When OA was pre
      mixed with meibum, but was absent from the subphase, it caused gradual
      concentration-dependent changes in the (pi/A) isotherms, but the MLF did not
      disappear from the surface. Thus, tested FFA showed a remarkable ability to
      disrupt, and/or prevent the formation of, human MLF, which could contribute to
      the onset of those forms of dry eye disease that are associated with enhanced
      activity of lipolytic enzymes, such as chronic blepharitis.

PMID- 21718697
TI  - Toxoplasma gondii: myenteric neurons of intraperitoneally inoculated rats show
      quantitative and morphometric alterations.
AB  - Several studies have demonstrated that the myenteric plexus experiences
      quantitative and morphometric changes in rats inoculated orally with Toxoplasma
      gondii. This paper aims to verify if these alterations are also seen when the
      same animals are inoculated intraperitoneally with the parasite. In order to do
      that, six Wistar rats (Rattus norvegicus) 60 days of age were infected
      intraperitoneally with 10(6) tachyzoites of a genotype I T. gondii strain (BTU
      IV). After 60 days, the animals were anaesthetised and underwent laparotomy. All
      organs from the small and large intestines were removed, measured, dissected and
      underwent whole-mount Giemsa technique to stain the neurons in the myenteric
      plexus. A quantitative and morphometric analysis of these cells was made, and it
      showed that the parasite causes the death of myenteric neurons in the jejunum and
      morphometric alterations in these cells throughout the intestine. However, the
      cellular response of myenteric neurons to T. gondii is heterogeneous compared the
      different organs from the gut.

PMID- 21718698
TI  - Tree-based delimitation of morphologically ambiguous taxa: a study of the lizard
      malaria parasites on the Caribbean island of Hispaniola.
AB  - Malaria parasites in the genus Plasmodium have been classified primarily on the
      basis of differences in morphology. These single-celled organisms often lack
      distinguishing morphological features, and this can encumber both species
      delimitation and identification. Six saurian malaria parasites have been
      described from the Caribbean island of Hispaniola. All six infect lizards in the
      genus Anolis, but only two of these parasites can be distinguished using
      morphology. The remaining four species overlap in morphology and geography, and
      cannot be consistently identified using traditional methods. We compared a
      morphological approach with a molecular phylogenetic approach for assessing the
      taxonomy of these parasites. We surveyed for blood parasites from 677 Anolis
      lizards, representing 26 Anolis spp. from a total of 52 sites across Hispaniola.
      Fifty-five of these lizards were infected with Plasmodium spp., representing
      several new host records, but only 24 of these infections could be matched to
      previously described species using traditional morphological criteria. We then
      estimated the phylogeny of these parasites using both mitochondrial (cytb and
      coxI) and nuclear (EF2) genes, and included carefully selected GenBank sequences
      to confirm identities for certain species. Our molecular results unambiguously
      corroborated our morphology-based species identifications for only the two
      species previously judged to be morphologically distinctive. The remaining
      infections fell into two well-supported and reciprocally monophyletic clades,
      which contained the morphological variation previously reported for all four of
      the morphologically ambiguous species. One of these clades was identified as
      Plasmodium floridense and the other as Plasmodium fairchildi hispaniolae. We
      elevate the latter to Plasmodium hispaniolae comb. nov. because it is
      polyphyletic with the mainland species Plasmodium fairchildifairchildi and we
      contribute additional morphological and molecular characters for future species
      delimitation. Our phylogenetic hypotheses indicate that two currently recognised
      taxa, Plasmodium minasense anolisi and Plasmodium tropiduri caribbense, are not
      valid on Hispaniola. These results illustrate that molecular data can improve
      taxonomic hypotheses in Plasmodium when reliable morphological characters are
      lacking.

PMID- 21718699
TI  - Synergetic chemiluminescence and label-free dual detection for developing a
      hepatitis protein array.
AB  - A dual detection system for protein arrays is presented that combines label-free
      detection by optical interference with chemiluminescence. A planar protein array
      that targets hepatitis B surface antigen is developed. Surface densities for
      individual antibody spots are quantitated using optical interference prior to
      use. Target binding (10 ng/ml) is detected label-free. Target binding (1 ng/ml)
      is detected by both optical interference and chemiluminescence with the inclusion
      of secondary antibodies. Binding results using both methods are found to be
      directly proportion to the capture probe density measured initially. The dual
      detection system provides the analytical utility of optical interference
      detection with the established clinical utility of chemiluminescence detection.

PMID- 21718700
TI  - Myosins and DYNLL1/LC8 in the honey bee (Apis mellifera L.) brain.
AB  - Honey bees have brain structures with specialized and developed systems of
      communication that account for memory, learning capacity and behavioral
      organization with a set of genes homologous to vertebrate genes. Many microtubule
      and actin-based molecular motors are involved in axonal/dendritic transport.
      Myosin-Va is present in the honey bee Apis mellifera nervous system of the larvae
      and adult castes and subcastes. DYNLL1/LC8 and myosin-IIb, -VI and -IXb have also
      been detected in the adult brain. SNARE proteins, such as CaMKII, clathrin,
      syntaxin, SNAP25, munc18, synaptophysin and synaptotagmin, are also expressed in
      the honey bee brain. Honey bee myosin-Va displayed ATP-dependent solubility and
      was associated with DYNLL1/LC8 and SNARE proteins in the membrane vesicle
      enriched fraction. Myosin-Va expression was also decreased after the
      intracerebral injection of melittin and NMDA. The immunolocalization of myosin-Va
      and -IV, DYNLL1/LC8, and synaptophysin in mushroom bodies, and optical and
      antennal lobes was compared with the brain morphology based on Neo-Timm
      histochemistry and revealed a distinct and punctate distribution. This result
      suggested that the pattern of localization is associated with neuron function.
      Therefore, our data indicated that the roles of myosins, DYNLL1/LC8, and SNARE
      proteins in the nervous and visual systems of honey bees should be further
      studied under different developmental, caste and behavioral conditions.

PMID- 21718701
TI  - NMR-based substrate analog docking to Escherichia coli peptidyl-tRNA hydrolase.
AB  - Escherichia coli peptidyl-tRNA hydrolase activity is inhibited by 3'-(L-[N,N
      diacetyl-lysinyl)amino-3'-deoxyadenosine, a stable mimic of the minimalist
      substrate 2'(3')-O-(L-[N,N-diacetyl-lysinyl)adenosine. The complex of this mimic
      with the enzyme has been analyzed by NMR spectroscopy, enabling experimental
      mapping of the catalytic center for the first time. Chemical shift variations
      point out the sensitivity of residues Asn10, Met67, Asn68, Gly111, Asn114,
      Leu116, Lys117, Gly147, Phe148, and Val149 to complex formation. Docking
      simulations based on ambiguous interaction restraints involving these residues
      show bondings of the peptide moiety of 3'-(l-[N,N-diacetyl-lysinyl)amino-3'
      deoxyadenosine with Asn10, Asn68, and Asn114. A stacking interaction of Phe66
      with the purine is also indicated. Drawn is a model of enzyme-bound peptidyl-tRNA
      substrate, in which: (i) the Asn114 delta(2) NH(2) group holds the water molecule
      that participates in the hydrolysis of the substrate, while Tyr15 binds the
      phosphate in the 5'-position of the 3'-terminal tRNA adenosine; (ii) the delta(2)
      NH(2) group of Asn68 holds the main-chain carbonyl of the C-terminal residue of
      the peptide esterified to tRNA; and (iii) the delta(2) NH(2) group of Asn10 holds
      the main-chain carbonyl of the penultimate C-residue. Functional value is given
      to this model by (i) showing that the enzyme becomes confusable with an aminoacyl
      tRNA hydrolase upon mutagenesis of Asn10 and (ii) reinterpreting already obtained
      site-directed mutagenesis data.

PMID- 21718702
TI  - Structured regions of alpha-synuclein fibrils include the early-onset Parkinson's
      disease mutation sites.
AB  - alpha-Synuclein (AS) fibrils are the major component of Lewy bodies, the
      pathological hallmark of Parkinson's disease (PD). Here, we use results from an
      extensive investigation employing solid-state NMR to present a detailed
      structural characterization and conformational dynamics quantification of full
      length AS fibrils. Our results show that the core extends with a repeated
      structural motif. This result disagrees with the previously proposed fold of AS
      fibrils obtained with limited solid-state NMR data. Additionally, our results
      demonstrate that the three single point mutations associated with early-onset PD
      A30P, E46K and A53T-are located in structured regions. We find that E46K and A53T
      mutations, located in rigid beta-strands of the wild-type fibrils, are associated
      with major and minor structural perturbations, respectively.

PMID- 21718703
TI  - The physical and functional thermal sensitivity of bacterial chemoreceptors.
AB  - The bacterium Escherichia coli exhibits chemotactic behavior at temperatures
      ranging from approximately 20  degrees C to at least 42  degrees C. This behavior
      is controlled by clusters of transmembrane chemoreceptors made from trimers of
      dimers that are linked together by cross-binding to cytoplasmic components. By
      detecting fluorescence energy transfer between various components of this system,
      we studied the underlying molecular behavior of these receptors in vivo and
      throughout their operating temperature range. We reveal a sharp modulation in the
      conformation of unclustered and clustered receptor trimers and, consequently, in
      kinase activity output. These modulations occurred at a characteristic
      temperature that depended on clustering and were lower for receptors at lower
      adaptational states. However, in the presence of dynamic adaptation, the response
      of kinase activity to a stimulus was sustained up to 45  degrees C, but
      sensitivity notably decreased. Thus, this molecular system exhibits a clear
      thermal sensitivity that emerges at the level of receptor trimers, but both
      receptor clustering and adaptation support the overall robust operation of the
      system at elevated temperatures.

PMID- 21718704
TI  - Markovian and non-Markovian protein sequence evolution: aggregated Markov process
      models.
AB  - Over the years, there have been claims that evolution proceeds according to
      systematically different processes over different timescales and that protein
      evolution behaves in a non-Markovian manner. On the other hand, Markov models are
      fundamental to many applications in evolutionary studies. Apparent non-Markovian
      or time-dependent behavior has been attributed to influence of the genetic code
      at short timescales and dominance of physicochemical properties of the amino
      acids at long timescales. However, any long time period is simply the
      accumulation of many short time periods, and it remains unclear why evolution
      should appear to act systematically differently across the range of timescales
      studied. We show that the observed time-dependent behavior can be explained
      qualitatively by modeling protein sequence evolution as an aggregated Markov
      process (AMP): a time-homogeneous Markovian substitution model observed only at
      the level of the amino acids encoded by the protein-coding DNA sequence. The
      study of AMPs sheds new light on the relationship between amino acid-level and
      codon-level models of sequence evolution, and our results suggest that protein
      evolution should be modeled at the codon level rather than using amino acid
      substitution models.

PMID- 21718705
TI  - The disposition of the LZCC protein residues in wenxiang diagram provides new
      insights into the protein-protein interaction mechanism.
AB  - Wenxiang diagram is a new two-dimensional representation that characterizes the
      disposition of hydrophobic and hydrophilic residues in alpha-helices. In this
      research, the hydrophobic and hydrophilic residues of two leucine zipper coiled
      coil (LZCC) structural proteins, cGKIalpha(1-59) and MBS(CT35) are dispositioned
      on the wenxiang diagrams according to heptad repeat pattern (abcdefg)(n),
      respectively. Their wenxiang diagrams clearly demonstrate that the residues with
      same repeat letters are laid on same side of the spiral diagrams, where most
      hydrophobic residues are positioned at a and d, and most hydrophilic residues are
      localized on b, c, e, f and g polar position regions. The wenxiang diagrams of a
      dimetric LZCC can be represented by the combination of two monomeric wenxiang
      diagrams, and the wenxiang diagrams of the two LZCC (tetramer) complex structures
      can also be assembled by using two pairs of their wenxiang diagrams. Furthermore,
      by comparing the wenxiang diagrams of cGKIalpha(1-59) and MBS(CT35), the
      interaction between cGKIalpha(1-59) and MBS(CT35) is suggested to be weaker. By
      analyzing the wenxiang diagram of the cGKIalpha(1-59.).MBS(CT42) complex
      structure, most affected residues of cGKIalpha(1-59) by the interaction with
      MBS(CT42) are proposed at positions d, a, e and g of the LZCC structure. These
      findings are consistent with our previous NMR results. Incorporating NMR
      spectroscopy, the wenxiang diagrams of LZCC structures may provide novel insights
      into the interaction mechanisms between dimeric, trimeric, tetrameric coiled-coil
      structures.

PMID- 21718706
TI  - Matrix metalloprotease-9 induces transforming growth factor-beta(1) production in
      airway epithelium via activation of epidermal growth factor receptors.
AB  - AIMS: Matrix metalloprotease (MMP)-9 is present in abundance in various chronic
      airway disorders and is involved in lung remodeling. MMP may cleave membrane
      bound precursor proteins and release epidermal growth factor-like ligands that
      subsequently bind to epidermal growth factor receptor (EGFR). We hypothesized
      that MMP-9 may stimulate the airway epithelium to produce fibrogenic mediators
      through activation of membrane-bound receptors. MAIN METHODS: Human airway
      epithelial cells were grown on air-liquid interface culture inserts. MMP-9 was
      employed to stimulate the cells. Conditioned medium following MMP-9 stimulation
      was co-incubated with human lung fibroblasts. KEY FINDINGS: MMP-9 stimulated
      human airway epithelial cells to produce transforming growth factor (TGF)-beta(1)
      at both the mRNA and protein level. Using a microarray, increased phosphorylation
      of EGFR tyrosine kinase (TK) was identified and further confirmed by
      immunoprecipitation and Western blot analysis. A significant increase in EGF and
      TGF-alpha release was observed after MMP-9 had been added for 30min. Protease
      inhibitor, EGFR monoclonal antibody and EGFR-TK inhibitor blocked this action and
      subsequent TGF-beta(1) production. Neutralizing antibodies against EGF and TGF
      alpha substantially inhibited TGF-beta(1) production following MMP-9 stimulation.
      MMP-9-induced TGF-beta(1) production occurred through MAP kinase p44/42
      phosphorylation. Selective p44/42 kinase inhibitor UO126 successfully inhibited
      TGF-beta(1) production. Conditioned medium from epithelial cells treated with MMP
      9 significantly induced Smad3 phosphorylation and subsequent fibroblast
      proliferation after 24h culture. SIGNIFICANCE: These data indicate that MMP-9
      induces TGF-beta(1) production in the airway epithelium through the cleavage of
      EGF and EGF-like ligands and activating EGFR, suggesting potential targets of
      therapeutic intervention in airway fibrotic disorders.

PMID- 21718707
TI  - Dietary phytoestrogens maintain contractile responses to carbachol with age in
      the female rat isolated bladder.
AB  - AIMS: Development of urinary incontinence, for many women, occurs following
      menopause. Dietary phytoestrogens consumed over the long term may affect the
      contractile function and maintenance of the urinary bladder in post menopausal
      women. This study examined the muscarinic receptor mediated contractile responses
      in the rat isolated bladder in response to ovariectomy and long term dietary
      phytoestrogen consumption. MAIN METHODS: Ovariectomised or sham-operated female
      Wistar rats (8 weeks) were fed either normal rat chow (soy, phytoestrogens) or a
      non-soy (phytoestrogen free) diet. Bladders were dissected from rats at 12, 24
      and 52 weeks of age and placed in 25 ml organ baths filled with McEwans solution.
      KEY FINDINGS: The contractile response to carbachol, in 12 week old female rats
      did not change as a result of dietary phytoestrogens or ovariectomy (P>0.05). At
      24 weeks of age, detrusor muscle strip responses to carbachol from non-soy fed
      ovariectomised rats were attenuated (P<0.05). At 52 weeks, bladder detrusor strip
      responses to carbachol were reduced in all treatment groups with the exception of
      the soy-fed sham operated rats. SIGNIFICANCE: These results suggest an age
      related reduction in the contractile response of the detrusor to the muscarinic
      receptor agonist carbachol, which may be prevented by long term dietary
      phytoestrogen intake.

PMID- 21718708
TI  - Bone marrow mononuclear cells reduce seizure frequency and improve cognitive
      outcome in chronic epileptic rats.
AB  - AIMS: Epilepsy affects 0.5-1% of the world's population, and approximately a
      third of these patients are refractory to current medication. Given their ability
      to proliferate, differentiate and regenerate tissues, stem cells could restore
      neural circuits lost during the course of the disease and reestablish the
      physiological excitability of neurons. This study verified the therapeutic
      potential of bone marrow mononuclear cells (BMMCs) on seizure control and
      cognitive impairment caused by experimentally induced epilepsy. MAIN METHODS:
      Status epilepticus (SE) was induced by lithium-pilocarpine injection and
      controlled with diazepam 90 min after SE onset. Lithium-pilocarpine-treated rats
      were intravenously transplanted 22 days after SE with BMMCs obtained from
      enhanced green fluorescent protein (eGFP) transgenic C57BL/6 mice. Control
      epileptic animals were given an equivalent volume of saline or fibroblast
      injections. Animals were video-monitored for the presence of spontaneous
      recurrent seizures prior to and following the cell administration procedure. In
      addition, rats underwent cognitive evaluation using a Morris water maze. KEY
      FINDINGS: Our data show that BMMCs reduced the frequency of seizures and improved
      the learning and long-term spatial memory impairments of epileptic rats. EGFP
      positive cells were detected in the brains of transplanted animals by PCR
      analysis. SIGNIFICANCE: The positive behavioral effects observed in our study
      indicate that BMMCs could represent a promising therapeutic option in the
      management of chronic temporal lobe epilepsy.

PMID- 21718709
TI  - Human induced pluripotent cells resemble embryonic stem cells demonstrating
      enhanced levels of DNA repair and efficacy of nonhomologous end-joining.
AB  - To maintain the integrity of the organism, embryonic stem cells (ESC) need to
      maintain their genomic integrity in response to DNA damage. DNA double strand
      breaks (DSBs) are one of the most lethal forms of DNA damage and can have
      disastrous consequences if not repaired correctly, leading to cell death, genomic
      instability and cancer. How human ESC (hESC) maintain genomic integrity in
      response to agents that cause DSBs is relatively unclear. Adult somatic cells can
      be induced to "dedifferentiate" into induced pluripotent stem cells (iPSC) and
      reprogram into cells of all three germ layers. Whether iPSC have reprogrammed the
      DNA damage response is a critical question in regenerative medicine. Here, we
      show that hESC demonstrate high levels of endogenous reactive oxygen species
      (ROS) which can contribute to DNA damage and may arise from high levels of
      metabolic activity. To potentially counter genomic instability caused by DNA
      damage, we find that hESC employ two strategies: First, these cells have enhanced
      levels of DNA repair proteins, including those involved in repair of DSBs, and
      they demonstrate elevated nonhomologous end-joining (NHEJ) activity and repair
      efficacy, one of the main pathways for repairing DSBs. Second, they are
      hypersensitive to DNA damaging agents, as evidenced by a high level of apoptosis
      upon irradiation. Importantly, iPSC, unlike the parent cells they are derived
      from, mimic hESC in their ROS levels, cell cycle profiles, repair protein
      expression and NHEJ repair efficacy, indicating reprogramming of the DNA repair
      pathways. Human iPSC however show a partial apoptotic response to irradiation,
      compared to hESC. We suggest that DNA damage responses may constitute important
      markers for the efficacy of iPSC reprogramming.

PMID- 21718710
TI  - Dissociation of subtraction and multiplication in the right parietal cortex:
      evidence from intraoperative cortical electrostimulation.
AB  - Previous research has consistently shown that the left parietal cortex is
      critical for numerical processing, but the role of the right parietal lobe has
      been much less clear. This study used the intraoperative cortical electrical
      stimulation approach to investigate neural dissociation in the right parietal
      cortex for subtraction and multiplication. Results showed that multiplication (as
      well as picture naming) was not affected by the cortical electrical stimulation
      on all the targeted sites of the right parietal cortex as well as those of the
      right temporal cortex. In contrast, stimulation at three right parietal sites
      (two sites in the right inferior parietal lobule and one in the right angular
      gyrus) impaired performance on simple subtraction problems. This study provided
      the first evidence from an intraoperative cortical electrical stimulation study
      to show the dissociation of arithmetic operations in the right parietal cortex.
      This dissociation between subtraction and multiplication suggests that the right
      parietal cortex plays a more significant role in quantity processing
      (subtraction) than in verbal processing (multiplication) in numerical processing.

PMID- 21718711
TI  - Introduction to "The intestinal wall - THE regulatory interface in energy
      homeostasis".
AB  - New revelations that have revitalized obesity-related research using a peripheral
      approach prompted us to organize a workshop titled "The intestinal wall - THE
      regulatory interface in energy homeostasis," which was held June 20-25, 2010, in
      Ascona, Switzerland, at the Centro Stefano Franscini of the Swiss Federal
      Institute of Technology (ETH). Throughout an exciting week of seminars and
      discussions, the workshop brought together around 70 expert researchers and
      clinicians from around the world who attempted to evaluate and integrate many
      important aspects of the role of the digestive tract in the regulation of energy
      homeostasis at the molecular, cellular, and systemic levels, as well as the
      implications for the prevention or treatment of obesity.

PMID- 21718712
TI  - Effects of polymorphism for locally adapted genes on rates of neutral
      introgression in structured populations.
AB  - Adaptation to local conditions within demes balanced by migration can maintain
      polymorphisms for variants that reduce fitness in certain ecological contexts.
      Here, we address the effects of such polymorphisms on the rate of introgression
      of neutral marker genes, possibly genetically linked to targets of selection.
      Barriers to neutral gene flow are expected to increase with linkage to targets of
      local selection and with differences between demes in the frequencies of locally
      adapted alleles. This expectation is borne out under purifying and disruptive
      selection, regimes that promote monomorphism within demes. In contrast,
      overdominance within demes induces minimal barriers to neutral introgression even
      in the face of very large differences between demes in the frequencies of locally
      adapted alleles. Further, segregation distortion, a phenomenon observed in a
      number of interspecific hybrids, can in fact promote transmission by migrants to
      future generations at rates exceeding those of residents.

PMID- 21718713
TI  - Generalized population models and the nature of genetic drift.
AB  - The Wright-Fisher model of allele dynamics forms the basis for most theoretical
      and applied research in population genetics. Our understanding of genetic drift,
      and its role in suppressing the deterministic forces of Darwinian selection has
      relied on the specific form of sampling inherent to the Wright-Fisher model and
      its diffusion limit. Here we introduce and analyze a broad class of forward-time
      population models that share the same mean and variance as the Wright-Fisher
      model, but may otherwise differ. The proposed class unifies and further
      generalizes a number of population-genetic processes of recent interest,
      including the Lambda and Cannings processes. Even though these models all have
      the same variance effective population size, they encode a rich diversity of
      alternative forms of genetic drift, with significant consequences for allele
      dynamics. We characterize in detail the behavior of standard population-genetic
      quantities across this family of generalized models. Some quantities, such as
      heterozygosity, remain unchanged; but others, such as neutral absorption times
      and fixation probabilities under selection, deviate by orders of magnitude from
      the Wright-Fisher model. We show that generalized population models can produce
      startling phenomena that differ qualitatively from classical behavior - such as
      assured fixation of a new mutant despite the presence of genetic drift. We derive
      the forward-time continuum limits of the generalized processes, analogous to
      Kimura's diffusion limit of the Wright-Fisher process, and we discuss their
      relationships to the Kingman and non-Kingman coalescents. Finally, we demonstrate
      that some non-diffusive, generalized models are more likely, in certain respects,
      than the Wright-Fisher model itself, given empirical data from Drosophila
      populations.

PMID- 21718714
TI  - Toxicity and differential protein analysis following destruxin A treatment of
      Spodoptera litura (Lepidoptera: Noctuidae) SL-1 cells.
AB  - The cytotoxicity of a destruxin A (DA) treatment of Spodoptera litura SL-1 cells
      was investigated. An MTT assay showed that DA was highly toxic to SL-1 cells in a
      concentration- and time-dependent manner. The IC(50) values of DA, after 24 h and
      48 h of treatment, were 17.86 MUg/mL and 7.80 MUg/mL, respectively. Under
      inverted phase contrast microscopy (IPCM), it was found that prolonged treatment
      with DA could induce cell rounding, cellular membrane shrinking, formation of
      apoptotic bodies, vacuole appearance and cytoplasm leak out. Apoptosis induced by
      DA was further confirmed by fluorescence microscopy (FM) and flow cytometry (FCM)
      studies. SL-1 cells entered early apoptosis following a treatment with 2.5 MUg/mL
      DA and entered late apoptosis following a treatment with increasing
      concentrations of DA. Furthermore, two-dimensional gel electrophoresis (2-DE)
      analysis was used to identify 22 proteins which were differentially expressed
      (>=2-fold difference) between control cells and DA-treated cells, and the
      expression level of these proteins was significantly different between the
      treated and untreated cells. Our results suggest that these differentially
      expressed proteins may help explain the diverse biological effects caused by the
      destruxin A treatment of cells; additionally, some of the identified proteins may
      have roles in SL-1 cellular proliferation and apoptosis.

PMID- 21718715
TI  - Scyphozoan jellyfish venom metalloproteinases and their role in the cytotoxicity.
AB  - The present study, for the first time, comparatively investigated the enzymatic
      activities (proteases and hyaluronidases) in the venoms of four Scyphozoan
      jellyfish species, including Nemopilema nomurai, Rhopilema esculenta, Cyanea
      nozakii, and Aurelia aurita. For this, various zymographic analyses were
      performed using assay specific substrates. Interestingly, all the four jellyfish
      venoms showed gelatinolytic, caseinolytic, and fibrinolytic activities, each of
      which contains a multitude of enzyme components with molecular weights between 17
      and 130 kDa. These four jellyfish venoms demonstrated a huge variation in their
      proteolytic activities in quantitative and qualitative manner depending on the
      species. Most of these enzymatic activities were disappeared by the treatment of
      1,10-phenanthroline, suggesting they might be belonged to metalloproteinases.
      Toxicological significance of these venom proteases was examined by comparing
      their proteolytic activity and the cytotoxicity in NIH 3T3 cells. The relative
      cytotoxic potency was C. nozakii > N. nomurai > A. aurita > R. esculenta. The
      cytotoxicity of jellyfish venom shows a positive correlation with its overall
      proteolytic activity. The metalloproteinases appear to play an important role in
      the induction of jellyfish venom toxicities. In conclusion, the present report
      proposes a novel finding of Scyphozoan jellyfish venom metalloproteinases and
      their potential role in the cytotoxicity.

PMID- 21718716
TI  - Cardiac myocytes and local signaling in nano-domains.
AB  - It is well known that calcium-induced calcium-release in cardiac myocytes takes
      place in spatially restricted regions known as dyads, where discrete patches of
      junctional sarcoplasmic reticulum tightly associate with the t-tubule membrane.
      The dimensions of a dyad are so small that it contains only a few Ca2+ ions at
      any given time. Ca2+ signaling in the dyad is therefore noisy, and dominated by
      the Brownian motion of Ca2+ ions in a potential field. Remarkably, from this
      complexity emerges the integrated behavior of the myocyte in which, under normal
      conditions, precise control of Ca2+ release and muscle contraction is maintained
      over the life of the cell. This is but one example of how signal processing
      within the cardiac myocyte and other cells often occurs in small "nano-domains"
      where proteins and protein complexes interact at spatial dimensions on the order
      of ~1-10 nm and at time-scales on the order of nanoseconds to perform the
      functions of the cell. In this article, we will review several examples of local
      signaling in nano-domains, how it contributes to the integrative behavior of the
      cardiac myocyte, and present computational methods for modeling signal processing
      within these domains across differing spatio-temporal scales.

PMID- 21718717
TI  - Digital mammography screening: weighing reduced mortality against increased
      overdiagnosis.
AB  - OBJECTIVE: Digital mammography has been shown to increase the detection of ductal
      carcinoma in situ (DCIS) compared to screen-film mammography. The benefits and
      risks of such an increase were assessed. METHODS: Breast cancer detection rates
      were compared between 502,574 screen-film and 83,976 digital mammograms performed
      between 2004 and 2006 among Dutch screening participants. The detection rates
      were then modeled using a baseline model and two extreme models that respectively
      assumed a high rate of progression and no progression of preclinical DCIS to
      invasive cancer. With these models, breast cancer mortality and overdiagnosis
      were predicted. RESULTS: The DCIS detection rate was significantly higher at
      digital mammography (1.2 per 1000 mammograms (95% C.I. 1.0-1.5)) than at screen
      film mammography (0.7 per 1000 mammograms (95% C.I. 0.6-0.7)). Consequently, 287
      (range progressive- non progressive model: 1-598) extra breast cancer deaths per
      1,000,000 women (a 4.4% increase) were predicted to be prevented. An extra 401
      (range: 165-2271) cancers would be overdiagnosed (a 21% increase). CONCLUSION:
      Modeling predicted that digital mammography screening would further reduce breast
      cancer mortality by 4.4%, at a 21% increased overdiagnosis rate. The consequences
      of digital screening, however, are sensitive to underlying assumptions on the
      natural history of DCIS.

PMID- 21718718
TI  - Antioxidant and immunological activities of water-soluble polysaccharides from
      Aconitum kusnezoffii Reichb.
AB  - Aconitum kusnezoffii Reichb., one of the earliest recorded toxic species of genus
      Aconitum, has been used as traditional Chinese medicine and medicinal diet over
      the last 2500 years to treat heart failure congestion, neuralgia, rheumatism and
      gout, etc. In the present paper, four water-soluble polysaccharide fractions
      isolated from the tubers of A. kusnezoffii Reichb. were studied the antioxidant
      and immunological activities for the first time. In vitro antioxidant assays
      indicated that fraction WKCP-A had noticeable scavenging activities on DPPH
      radical, hydroxyl radical, superoxide anion, H(2)O(2) and self-oxidation of 1,2,3
      phentriol, ferrous ion-chelating ability and reducing power. Moreover, the in
      vivo immunological assay exhibited that fractions WKCP-A and WKHP could more
      significantly enhance splenic lymphocyte proliferation and macrophage
      phagocytosis than other fractions. Therefore, the water-soluble polysaccharides
      from A. kusnezoffii Reichb., especially WKCP-A, have the potential to be explored
      as novel natural antioxidants and immunostimulating agents for using in
      functional foods or medicine.

PMID- 21718719
TI  - A novel NMDA receptor glycine-site partial agonist, GLYX-13, has therapeutic
      potential for the treatment of autism.
AB  - Deficits in social approach behavior, rough-and-tumble play, and speech
      abnormalities are core features of autism that can be modeled in laboratory rats.
      Human twin studies show that autism has a strong genetic component, and a recent
      review has identified 99 genes that are dysregulated in human autism.
      Bioinformatic analysis of these 99 genes identified the NMDA receptor complex as
      a significant interaction hub based on protein-protein interactions. The NMDA
      receptor glycine site partial agonist d-cycloserine has been shown to treat the
      core symptom of social withdrawal in autistic children. Here, we show that rats
      selectively bred for low rates of play-induced pro-social ultrasonic
      vocalizations (USVs) can be used to model certain core symptoms of autism. Low
      line animals engage in less social contact time with conspecifics, show lower
      rates of play induced pro-social USVs, and show an increased proportion of non
      frequency modulated (i.e. monotonous) ultrasonic vocalizations, compared to non
      selectively bred random-line animals. Gene expression patterns in the low-line
      animals show significant enrichment in autism-associated genes and the NMDA
      receptor family was identified as a significant hub. Treatment of low-line
      animals with the NMDAR glycine site partial agonist GLYX-13 rescued the deficits
      in play-induced pro-social 50-kHz and reduced monotonous USVs. Thus, the NMDA
      receptor has been shown to play a functional role in autism, and GLYX-13 shows
      promise for the treatment of autism. We dedicate this paper to Ole Ivar Lovaas
      (May 8, 1927-August 2, 2010), a pioneer in the field of autism.

PMID- 21718720
TI  - Contribution of metabotropic GABA(B) receptors to neuronal network construction.
AB  - In the 1980s, Bowery and colleagues discovered the presence of a novel,
      bicuculline-resistant and baclofen-sensitive type of GABA receptor on peripheral
      nerve terminals, the GABA(B) receptor. Since this pioneering work, GABA(B)
      receptors have been identified in the Central Nervous System (CNS), where they
      provide an important inhibitory control of postsynaptic excitability and
      presynaptic transmitter release. GABA(B) receptors have been implicated in a
      number of important processes in the adult brain such as the regulation of
      synaptic plasticity and modulation of rhythmic activity. As a result of these
      studies, several potential therapeutic applications of GABA(B) receptor ligands
      have been identified. Recent advances have further shown that GABA(B) receptors
      play more than a classical inhibitory role in adult neurotransmission, and can in
      fact function as an important developmental signal early in life. Here we
      summarize current knowledge on the contribution of GABA(B) receptors to the
      construction and function of developing neuronal networks.

PMID- 21718721
TI  - The role of NTS2 in the development of tolerance to NT69L in mouse models for
      hypothermia and thermal analgesia.
AB  - NT69L is a neurotensin (NT)(8-13) analog that binds the two major NT receptors,
      NTS1 and NTS2, and elicits similar behavioral effects as endogenous NT. Tolerance
      develops rapidly to some, but not to all of NT69L's effects, and to date, little
      is known about the mechanisms responsible for this tolerance. The development of
      tolerance appears to be more prevalent in behavioral effects mediated by NTS1
      than by those mediated by NTS2, including hypothermia and thermal analgesia.
      However, we hypothesize that both NTS1 and NTS2 have important roles in mediating
      the effects of NT69L. Here, we investigate the role of NTS2 on NT69L-mediated
      hypothermia and thermal analgesia with the use of NTS2 knock-out mice. We show
      that tolerance develops to NT69L-mediated hypothermia and thermal analgesia
      following sub-chronic treatment in wild-type (WT) mice, and that NTS2 is
      necessary for the development of that tolerance. Additionally, we suggest
      potential means by which NTS2 influences these NT69L-mediated behaviors.

PMID- 21718723
TI  - Calcitonin gene-related peptide prevents blood-brain barrier injury and brain
      edema induced by focal cerebral ischemia reperfusion.
AB  - Cerebral ischemia is one of the diseases that most compromise the human species.
      Therapeutic recovery of blood-brain barrier (BBB) disruption represents a novel
      promising approach to reduce brain injury after stroke. To determine the effects
      of calcitonin gene-related peptide (CGRP) on the BBB participate in stroke
      progression, rat cerebral ischemia reperfusion injury was induced by a 2-hour
      left transient middle cerebral artery occlusion (MCAO) using an intraluminal
      filament, followed by 46h of reperfusion. CGRP (1MUg/ml) at the dose of 3MUg/kg
      (i.p.) was administered at the beginning of reperfusion. Subsequently, 48h after
      MCAO, arterial blood pressure, infarct volume, water content, BBB permeability,
      BBB ultrastructure, levels of aquaporin-4 (AQP4) and its mRNA were evaluated.
      CGRP could reduce arterial blood pressure (P<0.001), infarct volume (P<0.05),
      cerebral edema (P<0.01), BBB permeability (P<0.05), AQP4 mRNA expression (P<0.05)
      and AQP4 protein expression (P<0.01). Furthermore, CGRP treatment improved
      ultrastructural damage of capillary endothelium cells and decreased the loss of
      the tight junction observed by transmission electronic microscopy (TEM) after 46h
      of reperfusion. Our findings show that CGRP significantly reduced postischemic
      increase of brain edema with a 2-hour therapeutic window in the transient model
      of focal cerebral ischemia. Moreover, it seems that at least part of the anti
      edematous effects of CGRP is due to decrease of BBB disruption by improving
      ultrastructural damage of capillary endothelium cells, enhancing basal membrane,
      and inhibiting AQP4 and its mRNA over-expression. The data of the present study
      provide a new possible approach for acute stroke therapy by administration of
      CGRP.

PMID- 21718722
TI  - 5-HT1B mRNA expression after chronic social stress.
AB  - Chronic stress contributes to vulnerability for depression and drug addiction.
      The function of the serotonergic system has been found to be modified by chronic
      stress and these changes may play an important role in stress-related relapses to
      drug craving. The 5-HT(1B) receptor is expressed in nucleus accumbens (NAc)
      projection neurons and modulates drug reward mechanisms and there is evidence
      suggesting that stress alters the regulation and function of these receptors. To
      examine the role of these receptors in integrating the effects of stress on
      reward mechanisms, we examined whether chronic or acute social defeat stress
      (SDS) regulates 5-HT(1B) mRNA in dorsal and ventral striatum, regions that are
      critical for integrating the effects of environmental stressors on reward
      motivated behavior. In addition, 5-HT(1B) mRNA regulation in response to another
      acute stressor, inescapable tailshock, was measured. Our results indicate that
      intermittent and daily SDS procedures attenuated body weight gain, induced
      adrenal hypertrophy, and reduced the preference for saccharin, a sweet solution
      preferred by normal rats. There was a trend for daily, but not intermittent SDS
      to increase 5-HT(1B) receptor mRNA levels in nucleus accumbens. Therefore, in the
      next experiment, we examined daily SDS in greater detail and found that it
      increased 5-HT(1B) receptor mRNA expression in rostral nucleus accumbens shell,
      an area especially associated with reward functions. Neither acute SDS, nor acute
      tailshock stress had a significant impact on 5-HT(1B) mRNA expression in the
      striatum. Since increased 5-HT(1B) receptor expression in nucleus accumbens shell
      neurons can facilitate cocaine and alcohol reward mechanisms, this adaptation in
      endogenous 5-HT(1B) mRNA may be involved in the SDS-associated increase in
      vulnerability for developing addiction.

PMID- 21718724
TI  - Enhanced production of plasmid DNA by engineered Escherichia coli strains.
AB  - Escherichia coli strains VH33 (PTS- GalP+ strain displaying a strongly reduced
      overflow metabolism) and VH34 (additionally lacking the pyruvate kinase A) were
      evaluated for the production of a plasmid DNA (pDNA) vaccine. The parent (W3110)
      and mutant strains were cultured using 10 g of glucose/L. While the specific
      growth rates of the three strains were similar, they presented differences in the
      accumulation of acetate. W3110 accumulated up to 4 g/L of acetate, VH33 produced
      1.4 g/L, and VH34 only 0.78 g/L. VH33 and VH34 produced 76% and 300% more pDNA
      than W3110. Moreover, VH34 demanded 33% less oxygen than VH33 and W3110, which
      can be advantageous for large-scale applications.

PMID- 21718725
TI  - Heterologous pyc gene expression under various natural and engineered promoters
      in Escherichia coli for improved succinate production.
AB  - In this study, the expression level of the pyc gene from Lactococcus lactis was
      fine tuned to improve succinate production in Escherichia coli SBS550MG. IPTG
      induction in the cultures of SBS550MG with pHL413, a positive control plasmid
      previously constructed (Sanchez et al., 2005), gave drastically decreased PYC
      activity and succinate yield. We constructed several plasmids for the expression
      of pyc to change copy number and variant promoters. Among the constructs, as
      compared to pHL413, the PYC activity dropped significantly with the Plac, Ptac,
      Ptrc or native Ppyc promoters in medium or high copy vectors, which resulted in a
      decrease in succinate yield. Three constructs pThio12, pHL413-Km, and pHL413
      Km(lacIq-)N showed considerable PYC activity and improved succinate production in
      E. coli SBS550MG. The native Ppyc promoter was also modified in order to vary pyc
      expression levels by site-directed mutagenesis of the -10, -35, -44 regions, and
      the spacer regions between -10 to -35 and -35 to -44 regions. Out of 9 native
      promoter variants, the MIII variant resulted in a 20% increase in PYC activity,
      and improved succinate yield in SBS550MG. We also determined the copy number and
      stability of pHL413 and pHL413-Km. The two plasmids showed roughly the same copy
      number, but the pHL413-Km plasmid was relatively more stable. This study provides
      more understanding of the plasmid characteristics and fine tuning of the
      expression level of pyc for optimization of the succinate production processes.

PMID- 21718726
TI  - Iron in fatty liver and in the metabolic syndrome: a promising therapeutic
      target.
AB  - The dysmetabolic iron overload syndrome (DIOS) is now a frequent finding in the
      general population, as is detected in about one third of patients with
      nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome. The
      pathogenesis is related to altered regulation of iron transport associated with
      steatosis, insulin resistance, and subclinical inflammation, often in the
      presence of predisposing genetic factors. Evidence is accumulating that excessive
      body iron plays a causal role in insulin resistance through still undefined
      mechanisms that probably involve a reduced ability to burn carbohydrates and
      altered function of adipose tissue. Furthermore, DIOS may facilitate the
      evolution to type 2 diabetes by altering beta-cell function, the progression of
      cardiovascular disease by contributing to the recruitment and activation of
      macrophages within arterial lesions, and the natural history of liver disease by
      inducing oxidative stress in hepatocytes, activation of hepatic stellate cells,
      and malignant transformation by promotion of cell growth and DNA damage. Based on
      these premises, the association among DIOS, metabolic syndrome, and NAFLD is
      being investigated as a new risk factor to predict the development of overt
      cardiovascular and hepatic diseases, and possibly hepatocellular carcinoma, but
      most importantly, represents also a treatable condition. Indeed, iron depletion,
      most frequently achieved by phlebotomy, has been shown to decrease metabolic
      alterations and liver enzymes in controlled studies in NAFLD. Additional studies
      are warranted to evaluate the potential of iron reductive therapy on hard
      clinical outcomes in patients with DIOS.

PMID- 21718727
TI  - Imaging of the interaction of cancer cells and the lymphatic system.
AB  - A thorough understanding of the lymphatic system and its interaction with cancer
      cells is crucial to our ability to fight cancer metastasis. Efforts to study the
      lymphatic system had previously been limited by the inability to visualize the
      lymphatic system in vivo in real time. Fluorescence imaging can address these
      limitations and allow for visualization of lymphatic delivery and trafficking of
      cancer cells and potentially therapeutic agents as well. Here, we review recent
      articles in which antibody-fluorophore conjugates are used to label the lymphatic
      network and fluorescent proteins to label cancer cells in the evaluation of
      lymphatic delivery and imaging.

PMID- 21718729
TI  - Layer-by-layer self-assembled nanoshells for drug delivery.

PMID- 21718728
TI  - Advances in lymphatic imaging and drug delivery.
AB  - Cancer remains the second leading cause of death after heart disease in the US.
      While metastasized cancers such as breast, prostate, and colon are incurable,
      before their distant spread, these diseases have invaded the lymphatic system as
      a first step in their progression. Hence, proper evaluation of the disease state
      of the lymphatics which drain a tumor site is crucial to staging and the
      formation of a treatment plan. Current lymphatic imaging modalities with visible
      dyes and radionucleotide tracers offer limited sensitivity and poor resolution;
      however, newer tools using nanocarriers, quantum dots, and magnetic resonance
      imaging promise to vastly improve the staging of lymphatic spread without
      needless biopsies. Concurrent with the improvement of lymphatic imaging agents,
      has been the development of drug carriers that can localize chemotherapy to the
      lymphatic system, thus improving the treatment of localized disease while
      minimizing the exposure of healthy organs to cytotoxic drugs. This review will
      focus on the use of various nanoparticulate and polymeric systems that have been
      developed for imaging and drug delivery to the lymph system, how these new
      devices improve upon current technologies, and where further improvement is
      needed.

PMID- 21718730
TI  - Consumers' attitudes towards GM Free products in a European Region. The case of
      the Prefecture of Drama-Kavala-Xanthi in Greece.
AB  - This study aims to identify the factors that affect consumers purchasing
      behaviour towards food products that are free from Genetic Modified Organism (GM
      Free) in a European Region and more precisely in the Prefecture of Drama-Kavala
      Xanthi. Field interviews conducted in a random selected sample consisted of 337
      consumers in the cities of Drama, Kavala, Xanthi, in November and December of
      2009. Principal components analysis (PCA) was conducted in order to identify the
      factors that affect people in preferring consuming products that are GM Free. The
      factors that influence people in the study area to buy GM Free products are: (a)
      products' certification as GM Free or organic products, (b) interest about the
      protection of the environment and nutrition value, (c) marketing issues, and (d)
      price and quality. Furthermore, cluster and discriminant analysis identified two
      groups of consumers: (a) those are influenced by the product price, quality and
      marketing aspects and (b) those are interested in product's certification and
      environmental protection. Non parametric statistical bivariate techniques were
      performed to profile the identified groups of consumers regarding their personal
      characteristics and some other factors affecting their buying behaviour.

PMID- 21718732
TI  - Effects of chewing gum on short-term appetite regulation in moderately restrained
      eaters.
AB  - Orosensory stimulation is an important contributing factor to the development of
      satiation. Providing orosensory stimulation with few calories may satisfy
      appetite and help to suppress cravings for high energy snacks. This may be a
      useful strategy for those motivated to lose or maintain weight. The present study
      tested the hypothesis that chewing sweetened gum will reduce subjective appetite
      and subsequent snack intake in moderately restrained eaters. Within-subjects,
      repeated measures study, sixty healthy participants (53 women; body mass index,
      in kg/m(2): 26.2+/-4.5) came to the laboratory 4 times for a standard lunch.
      Immediately after this meal, participants rated hunger, appetite and cravings for
      sweet and salty snacks every hour until they returned to the laboratory 3 h later
      for snack. On two occasions during this 3 h period participants chewed gum for at
      least 15 min at hourly intervals (45 min) and on two occasions no gum was chewed.
      On two occasions salty snacks were offered and on two occasions sweet snacks were
      provided. A small but significant reduction in snack intake was observed, chewing
      gum reduced weight of snack consumed by 10% compared to no gum (p<0.05). Overall,
      chewing gum for at least 45 min significantly suppressed rated hunger, appetite
      and cravings for snacks and promoted fullness (p<0.05). This study demonstrated
      some benefit of chewing gum which could be of utility to those seeking an aid to
      appetite control.

PMID- 21718731
TI  - Males and females show differential brain activation to taste when hungry and
      sated in gustatory and reward areas.
AB  - Although males and females differ in eating behavior and prevalence rates for
      eating disorders and obesity, little is known about gender differences in
      cortical activation to pleasant and unpleasant pure tastes during the
      physiological states of hunger and satiety. Twenty-one healthy young adults (12
      females and 9 males) underwent two functional magnetic resonance imaging scans.
      Using four pure tastants of differing qualities (i.e., salty, sour, bitter,
      sweet), the present study examined gender differences in fMRI activation during
      two motivational states (hunger and satiety). There was greater change in fMRI
      activation from hunger to satiety in males than females in response to all tastes
      within the middle frontal gyrus (BA 10), insula, and cerebellum. Males also had
      greater change in activation from hunger to satiety, relative to females, in
      limbic regions including dorsal striatum, amygdala, parahippocampal gyrus, and
      posterior and anterior cingulate; however, activation was stimulus dependent,
      despite equivalent ratings in perceived pleasantness and intensity.
      Interestingly, males and females showed significant change from hunger to satiety
      in response to citric acid, suggesting that in addition to gender and
      physiological condition, stimulus quality is an important factor in taste fMRI
      activation. These gender differences may have implications for the
      pathophysiology of eating disorders and obesity.

PMID- 21718733
TI  - Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral
      tissues by prazosin.
AB  - Hyperresponsiveness to norepinephrine contributes to post-traumatic stress
      disorder (PTSD). Prazosin, a brain-active blocker of alpha(1)-adrenoceptors,
      originally used for the treatment of hypertension, has been reported to alleviate
      trauma nightmares, sleep disturbance and improve global clinical status in war
      veterans with PTSD. Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) may
      play a role in the pathophysiology and treatment of neuropsychiatric disorders
      such as major depression, and PTSD (an anxiety disorder). To investigate whether
      TRH or TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid
      residue) participate in the therapeutic effects of prazosin, male rats were
      injected with prazosin and these peptides then measured in brain and endocrine
      tissues. Prazosin stimulated TRH and TRH-like peptide release in those tissues
      with high alpha(1)-adrenoceptor levels suggesting that these peptides may play a
      role in the therapeutic effects of prazosin.

PMID- 21718734
TI  - TGF-beta/BMPs: crucial crossroad in neural autoimmune disorders.
AB  - Transforming growth factor beta (TGF-beta) has a crucial role in the
      differentiation of ectodermal cells to neural or epidermal precursors. TGF-beta
      and bone morphogenetic protein molecules (BMPs) are involved in many
      developmental processes, including cell proliferation and differentiation,
      apoptosis, mitotic arrest and intercellular interactions during morphogenesis.
      Additionally, the failure of central thymic tolerance mechanisms, leading to T
      cells with a skewed autoreactive response, is being described as a contributor in
      inflammatory processes in autoimmune diseases such as multiple sclerosis. Since
      TGF-beta and BMP proteins are crucial for the development of the neural system
      and the thymus, as well as for the differentiation of T cells, it is essential to
      further investigate their role in the pathophysiology of this disorder by using
      references from embryonic experimental research. Available literature in the
      TGF/BMP signalling cascade, mostly during embryonic development of the nervous
      system is being reviewed. An attempt is made to further elucidate a potential
      role of TGF/BMP signalling in the pathophysiology of MS. During demyelination,
      BMP signaling, through various molecular mechanisms, directs the development of
      the adult neural stem cell in the astrocyte rather than the oligodendrocyte
      direction, therefore inhibiting the repair process. Further understanding of the
      above relationships could lead to the development of potentially efficient
      therapies for MS in the future.

PMID- 21718735
TI  - Role of mesenchymal stem cells in neurogenesis and nervous system repair.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) are attractive candidates for
      use in regenerative medicine since they are easily accessible and can be readily
      expanded in vivo, and possess unique immunogenic properties. Moreover, these
      multipotent cells display intriguing environmental adaptability and secretory
      capacity. The ability of MSCs to migrate and engraft in a range of tissues has
      received significant attention. Evidence indicating that MSC transplantation
      results in functional improvement in animal models of neurological disorders has
      highlighted exciting potential for their use in neurological cell-based
      therapies. The manner in which MSCs elicit positive effects in the damaged
      nervous system remains unclear. Cell fusion and/or 'transdifferentiation'
      phenomena, by which MSCs have been proposed to adopt neural cell phenotypes,
      occur at very low frequency and are unlikely to fully account for observed
      neurological improvement. Alternatively, MSC-mediated neural recovery may result
      from the release of soluble molecules, with MSC-derived growth factors and
      extracellular matrix components influencing the activity of endogenous neural
      cells. This review discusses the potential of MSCs as candidates for use in
      therapies to treat neurological disorders and the molecular and cellular
      mechanisms by which they are understood to act.

PMID- 21718736
TI  - Co-expression of tetanus toxin fragment C in Escherichia coli with thioredoxin
      and its evaluation as an effective subunit vaccine candidate.
AB  - The receptor-binding domain of tetanus toxin (THc), which mediates the binding of
      the toxin to the nerve cells, is a candidate subunit vaccine against tetanus. In
      this study one synthetic gene encoding the THc was constructed and highly
      expressed in Escherichia coli by co-expression with thioredoxin (Trx). The
      purified THc-vaccinated mice were completely protected against an active toxin
      challenge in mouse models of disease and the potency of two doses of THc was
      comparable to that of three doses of toxoid vaccine. And a solid-phase assay
      showed that the anti-THc sera inhibited the binding of THc or toxoid to the
      ganglioside GT1b as the anti-tetanus toxoid sera. Furthermore, mice were
      vaccinated once or twice at four different dosages of THc and a dose-response was
      observed in both the antibody titer and protective efficacy with increasing
      dosage of THc and number of vaccinations. The data presented in the report showed
      that the recombinant THc expressed in E. coli is efficacious in protecting mice
      against challenge with tetanus toxin suggesting that the THc protein may be
      developed into a human subunit vaccine candidate designed for the prevention of
      tetanus.

PMID- 21718737
TI  - Immunogenicity assay validation for an HIV vaccine trial: high IFNgamma+/IL-2+
      CD8+ T cells background in healthy Thais.
AB  - In a vaccine trial, assays for vaccine immunogenicity if performed locally will
      strengthen local site, can save costs and avoid hurdles associated with specimen
      transport. Here we report the optimization and validation of an Intracellular
      Cytokine Staining (ICS) assay which was undertaken in preparation for a phase I
      HIV vaccine trial conducted in Thailand. Intra-, and inter-operator variability
      were easily established. However, while attempting to set population cut offs for
      a positive response we found 4/36 (11%) high background responses of IFNgamma(+)
      and/or IL-2(+) CD8(+) T cells (>1%) in normal healthy volunteers. The
      determinates of these unexpected responses were explored and minimized.

PMID- 21718738
TI  - Immunogenicity of the reduced-antigen-content dTpa vaccine (Boostrix((r))) in
      adults 55 years of age and over: a sub-analysis of four trials.
AB  - BACKGROUND: Older adults, especially those over 65 years, are at risk of more
      severe morbidity from diphtheria, tetanus and pertussis and may transmit
      pertussis to unvaccinated or not yet fully vaccinated infants, but data on their
      response to reduced-antigen-content tetanus, diphtheria and acellular pertussis
      (dTpa) vaccines are lacking. METHODS: A sub-analysis pooled immunogenicity
      results in 293 adults aged 55+ years (mean age 64.4 years) from four randomised,
      controlled clinical trials of dTpa vaccine (Boostrix((r)), GlaxoSmithKline
      Biologicals) with or without IPV co-administration, or dTpa-IPV (Boostrix((r))
      IPV). RESULTS: Seroprotective antibody levels were achieved by 82.8% for
      diphtheria and 94.5% for tetanus. For pertussis antigens, the booster response
      rate, defined as initially seronegative subjects [<5EU/mL] reaching >=5EU/mL; or
      a >=2-fold increase in antibody concentration if initially seropositive was 89.2%
      for pertussis toxoid, 95.8% for filamentous haemagglutinin and 94.5% for
      pertactin. Post-booster geometric mean concentrations (GMC) increased for all
      antigens. Post-booster anti-tetanus and anti-PRN GMCs tended to be higher in 55-
      to 64-year olds than in those aged 65+. CONCLUSION: Larger numbers of subjects
      over 75 years are needed to better define responses in advanced age, but these
      data suggest that a single booster dose of dTpa or dTpa-IPV induces good
      immunological responses in most, and that these vaccines could be readily
      integrated into existing programmes.

PMID- 21718739
TI  - An immunological comparison between lipidated and non-lipidated multivalent HIV-1
      peptides representing Gp120 and Gag hypervariable regions.
AB  - Despite the extensive efforts towards development of an effective HIV vaccine,
      major challenges surrounding vaccine design still exist. We have previously
      developed a unique multivalent HIV-1 candidate vaccine representing hypervariable
      Gp120 and Gag regions. This candidate vaccine was able to induce a broad cell
      mediated immune response in HLA-A2.1 mice and non-human primates against HIV-1
      subtypes A-F. Herein, the reactivity of each hypervariable peptide mixture within
      our candidate peptide vaccine was further characterized to optimize the final
      vaccine formulation for the future clinical studies. The binding of each
      hypervariable region to sera from HIV-infected individuals demonstrated a strong
      reactivity between the antibodies and hypervariable regions. In addition, 15
      groups of mice were immunized with adjuvant alone or each individual peptide
      mixture (lipidated or non-lipidated) to evaluate the ability of each variable
      region to induce humoral and cellular immune responses against HIV-1. A reactive
      HIV-1 specific immune response was detected among the immunized groups; however,
      mice receiving the Gag hypervariable regions demonstrated the highest frequency
      of cell-mediated immune responses.

PMID- 21718740
TI  - Plasmodium falciparum serine repeat antigen 5 (SE36) as a malaria vaccine
      candidate.
AB  - A devastating disease spread by mosquitoes with high-efficiency, malaria imposes
      an enormous burden for which no licensed vaccine currently exists. Although the
      genome complexity of the parasite has made vaccine development tenuous, an
      effective malaria vaccine would be a valuable tool for control, elimination and
      eventual eradication. The Plasmodium serine repeat antigen 5 (SERA5) is an
      abundant asexual blood stage antigen that does not show any antigenic variation
      and exhibits limited polymorphism, making it a suitable vaccine candidate.
      Identified by comparing the IgG status of people in endemic areas with protective
      immunity and those with malaria symptoms, the vaccine potential of the N-terminal
      domain of Plasmodium falciparum SERA5 is also strongly supported by experimental
      data and immune responses both measured in vitro and in animal challenge models.
      The current understanding of SERA5 will be presented, particularly in relation to
      its path towards clinical development. The review highlights lessons learned and
      sorts out issues upon which further research efforts are needed.

PMID- 21718741
TI  - Immune correlates of protection against yellow fever determined by passive
      immunization and challenge in the hamster model.
AB  - Live, attenuated yellow fever (YF) 17D vaccine is highly efficacious but causes
      rare, serious adverse events resulting from active replication in the host and
      direct viral injury to vital organs. We recently reported development of a
      potentially safer beta-propiolactone-inactivated whole virion YF vaccine (XRX
      001), which was highly immunogenic in mice, hamsters, monkeys, and humans
      [10,11]. To characterize the protective efficacy of neutralizing antibodies
      stimulated by the inactivated vaccine, graded doses of serum from hamsters
      immunized with inactivated XRX-001 or live 17D vaccine were transferred to
      hamsters by the intraperitoneal (IP) route 24h prior to virulent, viscerotropic
      YF virus challenge. Neutralizing antibody (PRNT(50)) titers were determined in
      the sera of treated animals 4h before challenge and 4 and 21 days after
      challenge. Neutralizing antibodies were shown to mediate protection. Animals
      having 50% plaque reduction neutralization test (PRNT(50)) titers of >=40 4h
      before challenge were completely protected from disease as evidenced by viremia,
      liver enzyme elevation, and protection against illness (weight change) and death.
      Passive titers of 10-20 were partially protective. Immunization with the XRX-001
      vaccine stimulated YF neutralizing antibodies that were equally effective (based
      on dose response) as antibodies stimulated by live 17D vaccine. The results will
      be useful in defining the level of seroprotection in clinical studies of new
      yellow fever vaccines.

PMID- 21718742
TI  - Immunogenicity of conjugate meningococcus C vaccine in pediatric solid organ
      transplant recipients.
AB  - The present study was aimed to evaluate the immunogenicity of a single dose of
      conjugate Meningococcus C (Men C) vaccine by analyzing the serum bactericidal
      antibody (SBA) titers in 10 pediatric solid organ transplant (SOT) patients. Four
      patients showed a delayed immune response after 1 month, but all patients
      demonstrated an increase of SBA titers after vaccination. A significant decrease
      of SBA titers was seen after 6 months. However, all patients maintained
      protective SBA titers (>=1:8) despite rapidly waning titers. For patients with
      significantly decreasing titers, a booster dose may be discussed with close
      monitoring of SBA titers over time.

PMID- 21718743
TI  - Developing vaccinology expertise for Africa: six years and counting.
AB  - There exists high quality evidence showing that interactive educational meetings
      and workshops can improve healthcare worker performance. This evidence formed the
      basis for establishing the annual African Vaccinology Course in 2005 at the
      University of Cape Town in South Africa. The course, which is designed to develop
      vaccinology expertise for Africa, covers relevant basic sciences pertaining to
      vaccine-preventable diseases such as epidemiology, immunology and microbiology;
      discusses specific vaccine-preventable diseases; provides information on vaccine
      safety, vaccination strategies and evaluation of vaccines; discusses new vaccines
      in the pipeline; and promotes vaccine advocacy. We hope that course alumni would
      become strong advocates for childhood immunisation in their respective countries.
      Such dedicated advocacy should contribute to reducing the time gap between the
      development of new vaccines and the formulation of policies enabling their
      introduction in African countries, as well as contributing to more equitable
      increase in immunisation coverage in our continent.

PMID- 21718744
TI  - A novel guinea pig model of Chlamydia trachomatis genital tract infection.
AB  - Genital Chlamydia trachomatis infections often result in pelvic inflammatory
      disease and sequelae including infertility and ectopic pregnancies. In addition
      to the already established murine models, the development of other animal models
      is necessary to study the safety and efficacy of prototype vaccine candidates.
      The intravaginal infection of guinea pigs with C. trachomatis has been tested in
      three independent studies. The first two studies investigated the effect of
      hormonal treatment of the animals prior to infection with serovars D and E. The
      results showed that estradiol treatment was required for sustained infection. The
      third study conducted an immunization-challenge experiment to explore the
      feasibility of measuring protection in this guinea pig model. C. trachomatis
      bacteria were sampled using vaginal swabs and measured by qPCR. Using
      immunohistochemistry the bacteria were detected in the oviducts 19 days post
      infection, indicating that the estradiol treatment resulted in ascending
      infection. Furthermore, immunization of guinea pigs with live EB formulated with
      ISCOM matrix led to reduction of cervico-vaginal shedding and diminished the
      severity of pathology. In this study we have developed a new guinea pig model of
      C. trachomatis female genital tract infection for the purpose of evaluating
      potential vaccine candidates.

PMID- 21718745
TI  - The potential impact of an HIV vaccine with limited protection on HIV incidence
      in Thailand: a modeling study.
AB  - BACKGROUND: The RV144 trial on the ALVAC/AIDSVAX candidate HIV vaccine, carried
      out in Thailand, showed short-lived protection against infection. METHODS: Using
      a deterministic compartmental model we explored the potential impact of this
      vaccine on heterosexual HIV transmission in Thailand. Both one-off vaccination
      strategies, as well as strategies with regular boosting, either annually or every
      two years, were explored. Both targeting the general adult population and
      prioritizing sex workers were modeled. The impact of risk compensation among high
      risk groups, as well as whether higher levels of safe sex in high risk groups
      could be an alternative to vaccination, was studied. RESULTS: One-off vaccination
      campaigns had only transient effects, and boosting appears to be a key component
      of successful vaccination campaigns. Intensive vaccination campaigns may reduce
      HIV incidence by up to 75% after 10 years of vaccination. Targeting only sex
      workers has a smaller impact but has a more favorable cost-benefit ratio. Risk
      compensation has the potential of undoing much of the benefits of a vaccination
      program and may even increase incidence. In contrast, higher levels of safe sex
      among sex workers would provide a viable alternative to vaccinating this group.
      DISCUSSION: The new vaccine holds promise for controlling HIV in Thailand and
      similar countries. In view of the short lived protection of the vaccine, regular
      boosting of immunity as well as avoidance of risk compensation are essential.
      Targeting sex workers would achieve the greatest reduction in incidence per
      vaccination and may be considered for expensive vaccines but its cost
      effectiveness has to be compared to alternatives.

PMID- 21718747
TI  - Human immunodeficiency virus (HIV) immunopathogenesis and vaccine development: a
      review.
AB  - The development of a safe, effective and globally affordable HIV vaccine offers
      the best hope for the future control of the HIV-1 pandemic. Since 1987, scores of
      candidate HIV-1 vaccines have been developed which elicited varying degrees of
      protective responses in nonhuman primate models, including DNA vaccines, subunit
      vaccines, live vectored recombinant vaccines and various prime-boost
      combinations. Four of these candidate vaccines have been tested for efficacy in
      human volunteers, but, to the exception of the recent RV144 Phase III trial in
      Thailand, which elicited a modest but statistically significant level of
      protection against infection, none has shown efficacy in preventing HIV-1
      infection or in controlling virus replication and delaying progression of disease
      in humans. Protection against infection was observed in the RV144 trial, but
      intensive research is needed to try to understand the protective immune
      mechanisms at stake. Building-up on the results of the RV144 trial and
      deciphering what possibly are the immune correlates of protection are the top
      research priorities of the moment, which will certainly accelerate the
      development of an highly effective vaccine that could be used in conjunction with
      other HIV prevention and treatment strategies. This article reviews the state of
      the art of HIV vaccine development and discusses the formidable scientific
      challenges met in this endeavor, in the context of a better understanding of the
      immunopathogenesis of the disease.

PMID- 21718748
TI  - Key factors associated with oral health-related quality of life (OHRQOL) in Hong
      Kong Chinese adults with orofacial pain.
AB  - OBJECTIVES: To investigate key factors associated with oral health-related
      quality of life (OHRQOL) of Hong Kong Chinese adults with orofacial pain (OFP)
      symptoms. METHODS: A cross-sectional study was conducted amongst a random sample
      of registered patients at a primary medical care teaching clinic in Hong Kong.
      Patients who were aged 35-70 years and had experienced OFP symptoms in the past 1
      month were included. The OHRQOL was assessed by the Chinese version of the Oral
      Health Impact Profile (OHIP-14). A structured questionnaire on OFP symptoms and
      characteristics in the past 1 month, the depression and non-specific physical
      symptoms (NPS) scale in the research diagnostic criteria for temporomandibular
      disorders (RDC/TMD) questionnaire, and questions about professional treatment and
      dental attendance were administered before a standard clinical assessment.
      Negative binomial regression with forward stepwise selection was used to
      investigate key factors associated with the OHIP-14 additive score. RESULTS: The
      mean OHIP-14 additive score of the 200 participants was 10.1 (SD 9.4). Regression
      analysis revealed that five independent factors were significantly associated
      with higher OHIP-14 additive scores (indicating a poorer OHRQOL): a higher pain
      scale rating in the past 1 month (p=0.001), OFP clinical classification as
      musculoligamentous/soft tissue (MST) or dentoalveolar (DA) instead of
      neurological/vascular (NV) (p<0.001), more frequent dental attendance (p=0.008),
      moderate/severe RDC/TMD depression (p=0.005) and moderate/severe RDC/TMD NPS with
      pain (p=0.003). CONCLUSION: Various factors were associated with OHRQOL and could
      have implications for the improvement of OHRQOL in people in the community who
      have OFP symptoms.

PMID- 21718746
TI  - Of mice and not humans: how reliable are animal models for evaluation of herpes
      CD8(+)-T cell-epitopes-based immunotherapeutic vaccine candidates?
AB  - Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2)-specific CD8(+) T cells
      that reside in sensory ganglia, appear to control recurrent herpetic disease by
      aborting or reducing spontaneous and sporadic reactivations of latent virus. A
      reliable animal model is the ultimate key factor to test the efficacy of
      therapeutic vaccines that boost the level and the quality of sensory ganglia
      resident CD8(+) T cells against spontaneous herpes reactivation from sensory
      neurons, yet its relevance has been often overlooked. Herpes vaccinologists are
      hesitant about using mouse as a model in pre-clinical development of therapeutic
      vaccines because they do not adequately mimic spontaneous viral shedding or
      recurrent symptomatic diseases, as occurs in human. Alternatives to mouse models
      are rabbits and guinea pigs in which reactivation arise spontaneously with
      clinical herpetic features relevant to human disease. However, while rabbits and
      guinea pigs develop spontaneous HSV reactivation and recurrent ocular and genital
      disease none of them can mount CD8(+) T cell responses specific to Human
      Leukocyte Antigen- (HLA-)restricted epitopes. In this review, we discuss the
      advantages and limitations of these animal models and describe a novel
      "humanized" HLA transgenic rabbit, which shows spontaneous HSV-1 reactivation,
      recurrent ocular disease and mounts CD8(+) T cell responses to HLA-restricted
      epitopes. Adequate investments are needed to develop reliable preclinical animal
      models, such as HLA class I and class II double transgenic rabbits and guinea
      pigs to balance the ethical and financial concerns associated with the rising
      number of unsuccessful clinical trials for therapeutic vaccine formulations
      tested in unreliable mouse models.

PMID- 21718749
TI  - Unlocking G-quadruplex: Effect of unlocked nucleic acid on G-quadruplex
      stability.
AB  - G-quadruplexes are common structural motifs in aptamers. UNA or unlocked nucleic
      acid is the latest nucleic acid modification. We have attempted to evaluate the
      impact of UNA modification on the structure and stability of G-quadruplex
      oligonucleotides for application in aptamer design. We show using CD spectroscopy
      that UNA modifications can cause structural transitions in some cases although
      they retain the inherent G-quadruplex signature. From UV melting studies we
      showed a position dependent effect of UNA modifications such that quadruplexes
      with UNA modified loops are further stabilized whereas UNA modifications in stem
      of the G-quadruplex significantly destabilize the structure. The impact of UNA
      modification on different nucleobases is also investigated. From the analysis of
      UV melting results, thermodynamic profile was computed and it was concluded that
      all the sequences are stable at 37  degrees C. Finally, a greater serum stability
      of the modified oligonucleotides in comparison with unmodified ones is also
      demonstrated. Overall, the position dependent effect of single UNA substitutions
      was observed and analysed.

PMID- 21718751
TI  - Chemosensory event-related potentials in alcoholism: a specific impairment for
      olfactory function.
AB  - Olfactory abilities are crucial in the development and maintenance of alcoholism,
      but while they have been widely explored in other psychiatric states, little is
      known concerning this sensorial modality among alcoholics. The present study
      explored the brain correlates of the olfaction deficit in alcoholism. Ten
      alcoholics and ten matched controls took part in psychophysical and
      electrophysiological olfactory testing. At behavioural level, we showed odor
      identification deficits in alcoholism, for orthonasal and retronasal testing.
      Electrophysiological data showed abnormalities (in latency and amplitude) for N1
      and P2 olfactory components among alcoholics, which constitutes the first
      description of the cerebral correlates of olfactory impairments in alcoholism.
      This deficit appears associated with alterations in the brain structures
      responsible for the secondary, "cognitive" processing of odors. These results
      underline the need to take into account olfactory deficits in clinical practice
      and in studies exploring brain correlates of craving by means of alcohol odors.

PMID- 21718750
TI  - Staging Alzheimer's disease progression with multimodality neuroimaging.
AB  - Rapid developments in medical neuroimaging have made it possible to reconstruct
      the trajectory of Alzheimer's disease (AD) as it spreads through the living
      brain. The current review focuses on the progressive signature of brain changes
      throughout the different stages of AD. We integrate recent findings on changes in
      cortical gray matter volume, white matter fiber tracts, neuropathological
      alterations, and brain metabolism assessed with molecular positron emission
      tomography (PET). Neurofibrillary tangles accumulate first in transentorhinal and
      cholinergic brain areas, and 4-D maps of cortical volume changes show early
      progressive temporo-parietal cortical thinning. Findings from diffusion tensor
      imaging (DTI) for assessment fiber tract integrity show cortical disconnection in
      corresponding brain networks. Importantly, the developmental trajectory of brain
      changes is not uniform and may be modulated by several factors such as onset of
      disease mechanisms, risk-associated and protective genes, converging comorbidity,
      and individual brain reserve. There is a general agreement between in vivo brain
      maps of cortical atrophy and amyloid pathology assessed through PET, reminiscent
      of post mortem histopathology studies that paved the way in the staging of AD.
      The association between in vivo and post mortem findings will clarify the
      temporal dynamics of pathophysiological alterations in the development of
      preclinical AD. This will be important in designing effective treatments that
      target specific underlying disease AD mechanisms.

PMID- 21718752
TI  - The association between parenting and attachment security is moderated by a
      polymorphism in the mineralocorticoid receptor gene: evidence for differential
      susceptibility.
AB  - Maternal sensitive responsiveness and extreme insensitivity only partly explain
      the variance in attachment security. Differences in attachment security may well
      be rooted in the interplay of genetic variations and environmental factors. The
      association between parenting (observed sensitive responsiveness and extreme
      insensitivity) and attachment security (assessed with the Strange Situation
      Procedure) was hypothesized to be moderated by genes involved in the regulation
      of the stress response: the glucocorticoid receptor (GR) and mineralocorticoid
      receptor (MR) genes. A significant G*E interaction was found: infants carrying
      the minor MR allele (G) were significantly more securely attached if their
      mothers showed more sensitive responsiveness and significantly less securely
      attached if their mothers showed more extremely insensitive behaviors. These
      associations were not significant for carriers of the AA genotype of MR. Findings
      are discussed from a differential susceptibility perspective.

PMID- 21718753
TI  - A formal approach to evolution as self-referential language.
AB  - The recursive, self-referential, character of evolutionary process can be
      restated through a 'language' model in which genes, gene expression, and
      environment are represented as interacting information sources. The approach uses
      the asymptotic limit theorems of information theory to provide powerful necessary
      conditions for punctuated evolutionary transitions that can themselves be
      expressed as highly structured large deviations having their own grammar and
      syntax. The methodology defines, in a sense, the riverbanks that constrain, but
      do not determine, the self-dynamic stream of evolutionary process.

PMID- 21718754
TI  - Inhibitors of diacylglycerol metabolism reduce time to the onset of glutamate
      release potentation by mGlu7 receptors.
AB  - At nerve terminals G protein coupled receptors modulate neurotransmitter release
      probability. We recently showed that prolonged activation of metabotropic
      glutamate receptor 7, mGlu7 receptor, potentiates glutamate release. This
      signalling involves phospholipase C activation via a pertussis toxin insensitive
      G protein, the hydrolysis of phosphatidylinositol (4,5)-bisphosphate, and the
      subsequent activation of the non-kinase diacylglycerol binding protein Munc13-1
      which primes synaptic vesicle for exocytosis at the active zone. Here we found
      that inhibitors of diacylglycerol metabolism (diacylglycerol kinase inhibitor II
      and diacylglycerol lipase inhibitor RHC80267) remarkably reduce the time of mGlu7
      receptor stimulation required for glutamate release potentiation in mice
      cerebrocortical nerve terminals. We conclude that changes in diacylglycerol
      levels at nerve terminals control the efficiency of the exocytotic release
      machinery.

PMID- 21718756
TI  - The biochemistry of asthma.
AB  - BACKGROUND: Asthma is not one disease. Different patients have biochemically
      distinct phenotypes. SCOPE OF REVIEW: Biomarker analysis was developed to
      identify inflammation in the asthmatic airway. It has led to a renewed interest
      in biochemical abnormalities in the asthmatic airway. The biochemical
      determinants of asthma heterogeneity are many. Examples include decreased
      activity of superoxide dismutases; increased activity of eosinophil peroxidase, S
      nitrosoglutathione reductase, and arginases; decreased airway pH; and increased
      levels of asymmetric dimethyl arginine. MAJOR CONCLUSIONS: New discoveries
      suggest that biomarkers such as exhaled nitric oxide reflect complex airway
      biochemistry. This biochemistry can be informative and therapeutically relevant.
      GENERAL SIGNIFICANCE: Improved understanding of airway biochemistry will lead to
      new tests to identify biochemically unique subpopulations of patients with
      asthma. It will also likely lead to new, targeted treatments for these specific
      asthma subpopulations. This article is part of a Special Issue entitled
      Biochemistry of Asthma.

PMID- 21718755
TI  - Nitric oxide metabolism in asthma pathophysiology.
AB  - BACKGROUND: Asthma, a chronic inflammatory disease is typically characterized by
      bronchoconstriction and airway hyper-reactivity. SCOPE OF REVIEW: A wealth of
      studies applying chemistry, molecular and cell biology to animal model systems
      and human asthma over the last decade has revealed that asthma is associated with
      increased synthesis of the gaseous molecule nitric oxide (NO). MAJOR CONCLUSION:
      The high NO levels in the oxidative environment of the asthmatic airway lead to
      greater formation of reactive nitrogen species (RNS) and subsequent oxidation and
      nitration of proteins, which adversely affect protein functions that are
      biologically relevant to chronic inflammation. In contrast to the high levels of
      NO and nitrated products, there are lower levels of beneficial S-nitrosothiols
      (RSNO), which mediate bronchodilation, due to greater enzymatic catabolism of
      RSNO in the asthmatic airways. GENERAL SIGNIFICANCE: This review discusses the
      rapidly accruing data linking metabolic products of NO as critical determinants
      in the chronic inflammation and airway reactivity of asthma. This article is part
      of a Special Issue entitled Biochemistry of Asthma.

PMID- 21718757
TI  - P/Q-type calcium channel ablation in a mice glycinergic synapse mediated by
      multiple types of Ca2+ channels alters transmitter release and short term
      plasticity.
AB  - Ca(v)2.1 channels (P/Q-type) play a prominent role in controlling
      neurotransmitter release. Transgenic mice in which the alpha1A pore-forming
      subunit of Ca(v)2.1 channels is ablated (KO) provide a powerful tool to study
      Ca(v)2.1 function in synaptic transmission in vivo. Whole-cell patch clamp was
      used to measure inhibitory glycinergic postsynaptic currents (IPSCs) from the
      lateral superior olive (LSO). Comparing wild-type (WT) and KO mice, we
      investigated the relevance of P/Q-type calcium channels at a glycinergic synapse
      mediated by multiple types of Ca(2+) channels, in opposition to synapses where
      only this type of Ca(2+) channels are in charge of transmitter release. We found
      that in KO mice, N-type and L-type Ca(2+) channels control synaptic transmission,
      resulting in a functional but reduced glycinergic transmitter release. Pair pulse
      facilitation of synaptic currents is retained in KO mice, even when synaptic
      transmission is driven by either N or L-type calcium channels alone, in contrast
      with lack of this phenomenon in other synapses which are exclusively mediated by
      P/Q-type channels. Thus, pointing a difference between P/Q- and N-type channels
      present in single or multiple types of calcium channels driven synapses.
      Significant alterations in short-term synaptic plasticity were observed. KO mice
      exhibited a stronger short term depression (STD) of IPSCs during repetitive
      stimulation at high frequency and recovered with a larger time constant compared
      to WT mice. Finally, transmitter release at the LSO synapse from KO mice was
      strongly modulated by presynaptic GTP-binding protein-coupled receptor gamma
      aminobutyric acid type B (GABA(B)).

PMID- 21718758
TI  - Chronic sleep restriction causes a decrease in hippocampal volume in adolescent
      rats, which is not explained by changes in glucocorticoid levels or neurogenesis.
AB  - Sleep loss strongly affects brain function and may even predispose susceptible
      individuals to psychiatric disorders. Since a recurrent lack of sleep frequently
      occurs during adolescence, it has been implicated in the rise in depression
      incidence during this particular period of life. One mechanism through which
      sleep loss may contribute to depressive symptomatology is by affecting
      hippocampal function. In this study, we examined the effects of sleep loss on
      hippocampal integrity at young age by subjecting adolescent male rats to chronic
      sleep restriction (SR) for 1 month from postnatal day 30 to 61. They were placed
      in slowly rotating drums for 20 h per day and were allowed 4 h of rest per day at
      the beginning of the light phase. Anxiety was measured using an open field and
      elevated plus maze test, while saccharine preference was used as an indication of
      anhedonia. All tests were performed after 1 and 4 weeks of SR. We further studied
      effects of SR on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the
      end of the experiment, brains were collected to measure hippocampal volume and
      neurogenesis. Behavior of the SR animals was not affected, except for a transient
      suppression of saccharine preference after 1 week of SR. Hippocampal volume was
      significantly reduced in SR rats compared to home cage and forced activity
      controls. This volume reduction was not paralleled by reduced levels of
      hippocampal neurogenesis and could neither be explained by elevated levels of
      glucocorticoids. Thus, our results indicate that insufficient sleep may be a
      causal factor in the reductions of hippocampal volume that have been reported in
      human sleep disorders and mood disorders. Since changes in HPA activity or
      neurogenesis are not causally implicated, sleep disturbance may affect
      hippocampal volume by other, possibly more direct mechanisms.

PMID- 21718759
TI  - Catching falling objects: the role of the cerebellum in processing sensory-motor
      errors that may influence updating of feedforward commands. An fMRI study.
AB  - The human motor system continuously adapts to changes in the environment by
      comparing differences between the brain's predicted outcome of a certain behavior
      and the observed outcome. This discrepancy signal triggers a sensory-motor error
      and it is assumed that the cerebellum is a key structure in updating this error
      and associated feedforward commands. Using fMRI, the aim of the present study was
      to determine the main cerebellar structures that are involved in the processing
      of sensory-motor errors and in updating feedforward commands when simply catching
      a falling ball without displacement of the hand. Subjects only grasped the ball
      with their fingers when receiving it in their hand. By contrasting functional
      imaging signal obtained in conditions in which it was possible and impossible to
      predict the weight of the ball, we aimed to highlight sensory-motor error
      processing which we expected to be more marked in the conditions without
      prediction (less accurate feedforward process or more important feedback
      corrections) with respect to conditions with prediction (more accurate
      feedforward process or less important feedback corrections). When catching a
      falling ball and the possibility of prediction about the ball weight was
      manipulated, our results showed that both the right and left cerebellum is
      engaged in processing sensory-motor errors. It may also be involved in updating
      feedforward motor commands, perhaps on a trial by trial basis. In addition, when
      subjects were blindfolded, we observed a similar network but centered in a more
      anterior portion of the right cerebellum and we noted the presence of a
      cerebellar-thalamo-prefrontral network that may be involved in cognitive
      prediction (rather than sensory prediction) about ball weight.

PMID- 21718760
TI  - Functional development of the vagal and glossopharyngeal nerve-related nuclei in
      the embryonic rat brainstem: optical mapping with a voltage-sensitive dye.
AB  - We investigated functional organization of the vagus nerve (N. X)- and
      glossopharyngeal nerve (N. IX)-related nuclei in the embryonic rat brainstem and
      compared their development and spatial distribution patterns, using multiple-site
      optical recording with a fast voltage-sensitive dye, NK2761. Intact brainstem
      preparations with N. X and N. IX attached were dissected from E13-E16 rat
      embryos, and electrical responses evoked by N. X/N. IX stimulation were optically
      recorded from many loci of the stained preparations. We analyzed optical
      waveforms and separated fast and slow optical signals corresponding to the
      antidromic/orthodromic action potentials and the excitatory postsynaptic
      potentials (EPSPs), respectively. We constructed contour line maps of signal
      amplitudes and identified motor and sensory nuclei of N. X and N. IX. In the N. X
      related motor nucleus (the dorsal motor nucleus of the vagus nerve: DMNV), the
      fast signals were distributed in multiple-peak patterns, suggesting that the
      neurons and/or their activity are not distributed uniformly within the motor
      nuclei at early developmental stages. In the sensory nucleus (the nucleus of the
      tractus solitarius: NTS), the EPSPs were first detected from E15 in normal
      physiological solution for both N. X and N. IX. The N. IX-related NTS partially
      overlapped with the N. X-related NTS, but the peak locations were different
      between these two nerves. The results obtained in this study suggest that
      functional organization of the N. X- and N. IX-related nuclei changes dynamically
      with development in the embryonic rat brainstem.

PMID- 21718761
TI  - Sucrose modifies c-fos mRNA expression in the brain of rats maintained on feeding
      schedules.
AB  - Food intake is regulated according to circadian activity, metabolic needs and the
      hedonic value of food. Rodents placed on a fixed feeding schedule show behavioral
      and physiological anticipation of mealtime referred to as food-anticipatory
      activity (FAA). FAA is driven by the food-entrainable oscillator (FEO), whose
      anatomical substrate is not yet known. Recent data have shown that restricted
      feeding schedules for regular chow and daily limited access to palatable food in
      free-feeding rats activate distinct brain regions during FAA. The combination of
      a deprivation regimen and scheduled access to palatable food may give rise to a
      more global anticipatory mechanism because the temporal cycles of energy balance
      would be strongly modulated by the incentive properties of palatable food;
      however, the neuronal response to this combined treatment is not yet known. The
      present study investigated how adding palatable sucrose to feeding schedules
      affects the pattern of brain c-fos mRNA expression during FAA (0-3 h) and 1 h
      following feeding. The rats maintained on scheduled chow access increased their
      daily chow intake, while the rats maintained on scheduled sucrose and chow mainly
      increased their daily sucrose intake. Adding sucrose to scheduled feeding
      displaced c-fos mRNA expression from the dorsomedial and paraventricular
      hypothalamic nuclei and posterior lateral hypothalamus (LH) to the prefrontal
      cortex, lateral septum, nucleus accumbens and anterior LH. During refeeding, the
      rats on scheduled sucrose demonstrated higher activation of the nucleus of the
      solitary tract. The present results suggest that palatable sucrose combined with
      restricted feeding schedules activate a distinct neuronal network compared to
      neuronal activation produced by scheduled access to regular chow. These data
      provide evidence that the brain may contain different food-oscillatory systems
      and that food palatability may shift the neuronal activity from the medial
      hypothalamus to the limbic and reward-related areas even at the negative
      metabolic state.

PMID- 21718762
TI  - The influence of behavioural context on Weddell seal (Leptonychotes weddellii)
      airborne mother-pup vocalisation.
AB  - Previous mammalian studies have demonstrated that varying levels of signaller
      arousal are frequently expressed through vocal behaviour. The potential for
      callers to convey their motivational state may ensure that recipient responses
      are appropriate to their needs. The current study investigated the influence of
      behavioural context on Weddell seal mother-pup vocalisation. Mother and pup call
      rates were calculated within five and seven behavioural contexts, respectively,
      and the acoustic characteristics of 69 pup calls were measured within four
      contexts (total calls = 276). Context significantly influenced the temporal
      patterning of calls, with reuniting mothers and pups and lone active pups
      emitting more calls than during mother-pup contact periods. Reuniting and lone
      pup calls were also characterised by longer durations, higher fundamental
      frequencies, and increased energy in upper harmonics. Results suggest that
      reunion events and lone pup searching are characterised by calls reflective of
      heightened arousal, compared with mother-pup contact periods.

PMID- 21718763
TI  - Alteration of microRNA expression in the process of mouse brain growth.
AB  - MicroRNAs (miRNAs) are a functional small non-coding RNA and play essential roles
      in gene regulation in development, differentiation and proliferation. In this
      study, we investigated expression profiles of miRNAs in the process of normal
      mouse brain growth from embryonic day 16.5 to ~19 months old by means of DNA
      microarray and reverse-transcription quantitative polymerase chain reaction, and
      we examined whether there was any association between the expression of miRNAs
      and brain growth. The results indicated that a major change in the expression of
      miRNAs occurred in the brain within the first week to the fourth week
      postnatally. The data also exhibited the miRNAs that gradually increased and
      decreased in their levels, over the course of brain growth. Therefore, the
      current study suggests that miRNAs are capable of becoming a useful biological
      marker for study of brain growth, and leads to the possibility that gene
      silencing involving miRNAs may participate in the process of brain growth and
      perhaps brain aging.

PMID- 21718764
TI  - Relation between 3435C>T multidrug resistance 1 gene polymorphism with high dose
      methylprednisolone treatment of childhood acute idiopathic thrombocytopenic
      purpura.
AB  - The current study was conducted to assess 3435C>T multidrug resistance 1 gene
      polymorphism and the efficacy of high dose methylprednisolone (HDMP) in childhood
      acute idiopathic thrombocytopenic purpura patients. METHODS: A total of 31
      childhood acute Idiopathic thrombocytopenic purpura patients (17 females, 14
      males) between the ages of 2 and 16 years of age were included in the study. High
      dose methylprednisolone was given at a dose of 30mg/kg/day for 3 days and
      20mg/kg/day for 4 days, consecutively and intravenously. Polymerase chain
      reaction-restriction fragment length polymorphism was used for the detection of
      C3435T single nucleotide polymorphism. Fragments obtained were 238bp to T/T
      genotype, 172bp and 60bp fragments to the C/C genotype, and 238bp, 172bp and 60bp
      to the C/T genotype. RESULTS: The distribution of CC, CT, and TT genotypes were
      19.0%, 61.3%, and 19.4%, respectively. Both allele frequencies of C and T were
      the same - 50%. There was no significant difference in genotype and allele
      distribution between the patients with ITP and the control group (chi(2)=0.84
      p=0.65, chi(2)=0.2 p=0.63, respectively). There were no significant differences
      in age, gender, and pre- and post-treatment platelet counts between CC, CT, and
      TT genotypes of the MDR gene. Response to treatment shows no significant
      difference between genotype and allele groups. CONCLUSION: In our study, there
      was no difference in the HDMP treatment response between MDR1 gene genotypes.
      However, it should be noted that this study includes a small group of patients.
      Our data should therefore be considered preliminary, awaiting further
      confirmatory studies on an expanded patient base.

PMID- 21718765
TI  - Metabolism of N2-(4-hydroxyphenyl)guanine, a DNA adduct formed from p
      benzoquinone, in rat.
AB  - Among numerous adducts formed by reaction of DNA with p-benzoquinone (p-BQ), an
      electrophilic metabolite of benzene, only N2-(4-hydroxyphenyl)guanine (N2HPG) has
      been confirmed in vivo. If excreted in urine N2HPG would be a candidate non
      invasive biomarker of the DNA damage caused by benzene. To test this hypothesis,
      biotransformation of N2HPG was studied in rats. Unchanged N2HPG in urine amounted
      to 8.0 +/- 2.2% and 9.1 +/- 1.7% (mean +/- SE) at the dose of 2 mg/kg excreted
      within 1 and 2 days after ip dosage, respectively. After acidic hydrolysis of the
      urine a slight but consistent increase in urinary N2HPG to 9.5 +/- 3.2% and 11 +/
      2.6% of dose was found within 1 and 2 days, respectively, indicating formation
      of hydrolysable conjugates. An oxidised metabolite was detected by LC-ESI-MS and
      identified by comparison with authentic standard as N2-(4-hydroxyphenyl)-8
      oxoguanine (N2HPOG). Its excretion amounted to 2.7 +/- 0.2% of dose and increased
      to 12.0 +/- 2.7% of dose when N2HPOG was released from its conjugates by acidic
      hydrolysis. Glucuronides and sulphates of both N2HPG and N2HPOG were confirmed in
      urine by LC-ESI-MS and by enzymatic treatment with glucuronidase/sulphatase.
      These results indicate an extensive metabolism of N2HPG in vivo, which must be
      taken into account when considering N2HPG as a possible biomarker of exposure to
      benzene.

PMID- 21718766
TI  - Asymmetric 1-alkyl-2-acyl phosphatidylcholine: a helper lipid for enhanced non
      viral gene delivery.
AB  - Rationally designed asymmetrical alkylacyl phosphatidylcholines (APC) have been
      synthesized and evaluated as helper lipids for non-viral gene delivery. A long
      aliphatic chain (C22-C24) was introduced at the 1-position of glycerol backbone,
      a branched lipid chain (C18) at the 2-position, and a phosphocholine head group
      at the 3-position. The fusogenicity of APC depends on the length and degree of
      saturation of the alkyl chain. Cationic lipids were formulated with APC as either
      lipoplexes or nanolipoparticles, and evaluated for their stability, transfection
      efficiency, and cytotoxicity. APC mediated high in vitro transfection efficiency,
      and had low cytotoxicity. Small nanolipoparticles (less than 100 nm) can be
      obtained with APC by applying as low as 0.1% PEG-lipid. Our study extends the
      type of helper lipids that are suitable for gene transfer and points the way to
      improve non-viral nucleic acid delivery system other than the traditional
      cationic lipids optimization.

PMID- 21718767
TI  - Initial moisture content in raw material can profoundly influence high shear wet
      granulation process.
AB  - The aim of this work is to demonstrate that uncontrolled initial moisture content
      in microcrystalline cellulose (MCC) can profoundly affect high shear wet
      granulation (HSWG) process. We show that granule tabletability is reduced by
      approximately 50% when initial moisture content in MCC increases from 0.9% to
      10.5% while all other processing parameters remain unchanged. An important
      observation is that granule tableting performance deteriorates significantly when
      initial moisture content increases from 2.6% to 4.9%, which is considered normal
      variation in moisture content for typical MCC (3-5%). The deteriorated
      tabletability is largely caused by increased granule size. On the other hand,
      granule flowability improves continuously with increasing initial moisture
      content in MCC. The improved flowability is mainly a result of granule size
      enlargement. Clearly, moisture content of raw materials for a HSWG process must
      be carefully monitored and controlled to ensure a robust manufacturing process as
      required by the quality-by-design principle.

PMID- 21718768
TI  - A method for the aerodynamic design of dry powder inhalers.
AB  - An inhaler design methodology was developed and then used to design a new dry
      powder inhaler (DPI) which aimed to fulfill two main performance requirements.
      The first requirement was that the patient should be able to completely empty the
      dry powder from the blister in which it is stored by inspiratory effort alone.
      The second requirement was that the flow resistance of the inhaler should be
      geared to optimum patient comfort. The emptying of a blister is a two-phase flow
      problem, whilst the adjustment of the flow resistance is an aerodynamic design
      problem. The core of the method comprised visualization of fluid and particle
      flow in upscaled prototypes operated in water. The prototypes and particles were
      upscaled so that dynamic similarity conditions were approximated as closely as
      possible. The initial step in the design method was to characterize different
      blister prototypes by measurements of their flow resistance and particle emptying
      performance. The blisters were then compared with regard to their aerodynamic
      performance and their ease of production. Following selection of candidate
      blisters, the other components such as needle, bypass and mouthpiece were
      dimensioned on the basis of node-loop operations and validation experiments. The
      final shape of the inhaler was achieved by experimental iteration.

PMID- 21718769
TI  - Protecting the auditory system with glucocorticoids.
AB  - Glucocorticoids are hormones released following stress-related events and
      function to maintain homeostasis. Glucocorticoid receptors localize, among
      others, to hair cells, spiral ligament and spiral ganglion neurons.
      Glucocorticoid receptor-induced protection against acoustic trauma is found by i)
      pretreatment with glucocorticoid agonists; ii) acute restraint stress; and iii)
      sound conditioning. In contrast, glucocorticoid receptor antagonists exacerbate
      hearing loss. These findings have important clinical significance since synthetic
      glucocorticoids are commonly used to treat hearing loss. However, this treatment
      has limited success since hearing improvement is often not maintained once the
      treatment has ended, a fact that reduces the overall appeal for this treatment.
      It must be realized that despite the widespread use of glucocorticoids to treat
      hearing disorders, the molecular mechanisms underlying this treatment are not
      well characterized. This review will give insight into some physiological and
      biochemical mechanisms underlying glucocorticoid treatment for preventing hearing
      loss.

PMID- 21718770
TI  - Prevention of experimental diabetes by Uncaria tomentosa extract: Th2
      polarization, regulatory T cell preservation or both?
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willd.) DC (Rubiaceae) is a
      species native to the Amazon rainforest and surrounding tropical areas that is
      endowed with immunomodulatory properties and widely used around the world. In
      this study we investigated the immunomodulatory potential of Uncaria tomentosa
      (UT) aqueous-ethanol extract on the progression of immune-mediated diabetes.
      MATERIALS AND METHODS: C57BL/6 male mice were injected with MLDS (40 mg/kg) and
      orally treated with UT at 10-400mg/kg during 21 days. Control groups received
      MLDS alone or the respective dilution vehicle. Pancreatic mononuclear infiltrate
      and beta-cell insulin content were analyzed by HE and immunohistochemical
      staining, respectively, and measured by digital morphometry. Lymphocyte
      immunophenotyping and cytokine production were determined by flow cytometry
      analysis. RESULTS: Treating the animals with 50-400mg/kg of UT caused a
      significant reduction in the glycemic levels, as well as in the incidence of
      diabetes. The morphometric analysis of insulitis revealed a clear protective
      effect. Animals treated with UT at 400mg/kg presented a higher number of intact
      islets and a significant inhibition of destructive insulitis. Furthermore, a
      significant protection against the loss of insulin-secreting presented beta-cells
      was achieved, as observed by a careful immunohistochemical evaluation. The
      phenotypic analysis indicated that the groups treated with higher doses (100
      400mg/kg) presented CD4(+) and CD8(+) T-cell values similar to those observed in
      healthy animals. These same higher doses also increased the number of
      CD4(+)CD25(+)Foxp3(+) regulatory T-cells. Moreover, the extract modulated the
      production of Th1 and Th2, with increased levels of IL-4 and IL-5. CONCLUSIONS:
      The extract was effective to prevent the progression of immune-mediated diabetes
      by distinct pathways.

PMID- 21718771
TI  - Metabonomic study on chronic unpredictable mild stress and intervention effects
      of Xiaoyaosan in rats using gas chromatography coupled with mass spectrometry.
AB  - ETHNOPHARMACOLOGY: Xiaoyaosan (XYS), a famous Chinese prescription, composed of
      Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica
      sinensis (Oliv.) Diels), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Rhizoma
      Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Poria (Poria cocos
      (Schw.) Wolf), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Herba Menthae
      (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale
      Rosc.), has been widely used in the clinic for treating mental disorders.
      Behavior and biochemical analyses indicate XYS has obvious anti-depression
      activity. However, there is no report on the effects of XYS using a metabolomics
      approach. AIM OF THE STUDY: Depression is a prevalent complex psychiatric
      disorder and its pathophysiological mechanism is not yet well understood. This
      paper was designed to study metabonomic characters of the depression induced by
      chronic unpredictable mild stress (CUMS) and the therapeutic effects of XYS,
      classic traditional Chinese medicine (TCM) in treating the depression. MATERIAL
      AND METHODS: A plasma metabonomics method based on gas chromatography/mass
      spectrometry (GC/MS) was developed. Principal component analysis (PCA) was
      utilized to classify and reveal the differences between the model group and
      control group. In turns, the concentration of these differences was analyzed with
      t-test to determine whether XYS was possible to influence the metabolic pattern
      induced by CUMS. RESULTS: The significant difference in metabolic profiling was
      observed from model group compared with drug-dose group by using the PCA,
      indicating the recovery effect of XYS on CUMS rats. Some significantly changed
      metabolites like glycine, glucose and hexadecanoic acid have been identified.
      These biochemical changes are related to the disturbance in amino acid
      metabolism, energy metabolism and glycometabolism, which are helpful to further
      understand the CUMS and the therapeutic mechanism of XYS. CONCLUSIONS:
      Metabonomic approach is helpful to further understanding the pathophysiology of
      depression and assisting in clinical diagnosis of depression and is also a
      valuable tool for studying the essence of Chinese medicine's syndrome theory and
      therapeutic effect mechanism of TCM.

PMID- 21718772
TI  - Water extract of Cynanchi atrati Radix regulates inflammation and apoptotic cell
      death through suppression of IKK-mediated NF-kappaB signaling.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchi atrati Radix has been traditionally used
      as an anti-inflammatory agent to treat febrile diseases, acute urinary infection
      or subcutaneous pyogenic infection with invasion of the pathogenic factors. AIM
      OF STUDY: Nuclear factor (NF)-kappaB is a pleiotropic transcriptional factor of
      many genes involved in inflammatory and anti-apoptotic responses. To identify a
      novel, potent inhibitor of NF-kappaB signaling pathway, a plant extract library
      of traditional oriental medicine was screened for the capability to block the NF
      kappaB activity in cells overexpressing toll-like receptor 4 (TLR4), and then
      evaluated the anti-inflammatory and pro-apoptotic functions of water extract of
      Cynanchi atrati Radix (WECR) in macrophages and cancer cells, respectively.
      MATERIALS AND METHODS: The effect of WECR on the proinflammatory mediators
      (inducible NO synthase [iNOS], cyclooxygenase [COX]-2), IkappaB-alpha
      degradation, RelA/p65 phosphorylation and caspase cleavages were measured by
      immunblotting. NF-kappaB transcriptional activity, IkappaB kinase (IKK) activity
      and nitric oxide (NO) production was measured using the luciferase assay, in
      vitro kinase assay and Griess reaction. RESULTS: WECR efficiently inhibited LPS
      induced expression of proinflammatory mediators including iNOS and COX-2. IKK
      kinase activity, IkappaB-alpha degradation, nuclear translocation of RelA/p65 and
      NF-kappaB transcriptional activity induced by LPS were suppressed by WECR.
      Furthermore, WECR dramatically enhances the apoptotic response, as evident by the
      combination with tumor necrosis factor (TNF) was able to induce the cytotoxic
      action through caspase-dependent pathway. CONCLUSION: These results indicate that
      WECR has a potential to inhibit IKK-mediated NF-kappaB activation, and is a
      valuable compound for modulating inflammatory or cancerous conditions.

PMID- 21718773
TI  - Aqueous extract of Gleditsia sinensis Lam. fruits improves serum and liver lipid
      profiles and attenuates atherosclerosis in rabbits fed a high-fat diet.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gleditsia sinensis Lam. has been used in the
      traditional Chinese medicine as a chief ingredient of many polyherbal
      formulations for the treatment of obesity and thrombosis. AIM OF THE STUDY: To
      evaluate the effects of Gleditsia sinensis Lam. fruit aqueous extract (GAE) on
      hyperlipidemia and atherosclerosis in Japanese white rabbits on a high fat diet.
      MATERIALS AND METHODS: Rabbits were divided into four groups: the normal control
      with a normal diet, and high-fat diet-fed model group and GAE-treated groups
      supplemented with GAE (6 or 12 mg/kg/day, p.o.), respectively. The groups fed
      high-fat diets were given i.v. with bovine serum albumin (BSA) on the 4th week to
      induce atherosclerosis. The serum lipid profile, including triglycerides (TG),
      total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), was
      determined on the 0th, 4th, 8th and 14th week, respectively. And the activities
      of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine
      kinase (CK) were measured simultaneously. At the end of the experiment, the
      rabbits were sacrificed, and the atherosclerotic plaques as well as the
      histopathological changes of aorta and liver were assessed by oil-red or HE
      staining, respectively, and the aorta and liver lipid profiles were also assayed.
      RESULTS: Results showed that the prophylactic treatment with GAE could
      significantly decrease the lipid levels of serum, aorta and liver, attenuate
      aortic atherosclerosis and improve aortic remodeling without the significant
      liver and muscle toxicity. CONCLUSION: The present findings suggest that GAE can
      effectively attenuate the atherosclerotic at least through anti-hyperlipidemic
      activity and thus has the therapeutic potential in treating hyperlipidemia
      related cardiovascular diseases.

PMID- 21718774
TI  - Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The use of an aqueous extract of coriander
      (Coriandrum sativum L.; Apiaceae, Umbelliferae) seeds (CS-extract) in Moroccan
      traditional treatment of diabetes remains to be experimentally validated. AIM OF
      THE STUDY: The study aim was to investigate potential hypoglycemic (and
      hypolipidemic) activity of CS-extract after a single oral dose and after daily
      dosing for 30 days (sub-chronic study) in normal and obese-hyperglycemic
      hyperlipidemic (OHH) Meriones shawi rats. MATERIALS AND METHODS: After a single
      oral dose of CS-extract (20mg/kg; predetermined as optimum), plasma glucose,
      insulin, total cholesterol (TC), and triglycerides (TG) were measured in normal
      and OHH rats (hypercaloric diet and forced limited physical activity);
      glibenclamide (GLB; 2.5mg/kg) was used as reference. In the sub-chronic study,
      the effect of CS-extract and GLB (at the above doses) on body weight (BW), plasma
      glucose, insulin, TC, LDL-cholesterol, HDL-cholesterol, TG, urea and creatinine
      was determined in normal and OHH rats; insulin resistance (IR as HOMA-IR),
      atherosclerotic and cardioprotective indices were calculated. RESULTS: A single
      dose of CS-extract or GLB suppressed hyperglycemia in OHH rats, and normo
      glycemia was achieved at 6-h post-dose; there was no effect on lipids, TG or
      insulin, but IR decreased significantly. The hypoglycemic effect was lower in
      normal rats. In the sub-chronic study in OHH rats, the test substances (CS
      extract>GLB) reduced plasma glucose (normoglycemia on Day 21), insulin and IR,
      TC, LDL-cholesterol, and TG. Atherosclerotic index decreased while
      cardioprotective indices increased only by CS-extract, with no effect on BW, urea
      or creatinine. CONCLUSION: Sub-chronic administration of CS-extract in OHH
      Meriones shawi rats normalized glycemia and decreased the elevated levels of
      insulin, IR, TC, LDL-cholesterol and TG. Since, the CS-extract decreased several
      components of the metabolic syndrome and decreased atherosclerotic and increased
      cardioprotective indices, CS-extract may have cardiovascular protective effect.
      The present study validates the traditional use of coriander in diabetes.

PMID- 21718775
TI  - Effects of Portulaca oleracea L. seeds in treatment of type-2 diabetes mellitus
      patients as adjunctive and alternative therapy.
AB  - ETHNPHARMACOLOGICAL RELEVANCE: To investigate antidiabetic activity of purslane
      seeds on type-2 diabetic subjects and to provide scientific basis for the
      clinical use of Portulaca oleracea (PO). MATERIALS AND METHODS: A thirty subject
      with type-2 diabetes divided into two groups, to receive 5 g of PO seeds twice
      daily while in the second group, their participants receive 1,500 mg of
      metformin/day. All participants were requested to report the effects of
      treatments on diabetic manifestations, their weights, body mass index (BMI),
      adverse effects, fasting and post-prandial blood glucose during treatment
      schedule. Blood samples from participants before and after treatment were taken
      for serum separation, which are used for measurement of serum lipids, liver
      enzymes, total and direct bilirubin, albumin, and insulin. RESULTS: It showed a
      significant decrease in serum levels of triglycerides (TGs), total cholesterol
      (T(C)), low density lipoprotein cholesterol (LDL(C)), liver alanine-, aspartate-
      and gamma glutamyl transaminase (ALT, AST, and GGT), total and direct bilirubin,
      fasting and post-prandial blood glucose, insulin, body weight and BMI while a
      significant increase in high density lipoprotein cholesterol (HDL(C)) and albumin
      but non-significant change of alkaline phosphatase (ALP) in PO seeds treated
      subjects. Metformin (M) group has the same results of PO group except in high
      density lipoprotein cholesterol (HDL(C)), LDL(C), and ALP levels had a different
      pattern. CONCLUSIONS: PO seeds could be effective and safe as adjuvant therapy
      for Type-2 diabetic subjects. These results demonstrated that PO seeds possessed
      notable hypoglycaemic, hypolipidaemic and insulin resistance reducer effects;
      possibly due to its contents of polyunsaturated fatty acids, flavonoids, and
      polysaccharides.

PMID- 21718776
TI  - Anti-diabetic activity and potential mechanism of total flavonoids of Selaginella
      tamariscina (Beauv.) Spring in rats induced by high fat diet and low dose STZ.
AB  - AIM OF THE STUDY: To evaluate the anti-diabetic effects of the total flavonoids
      of Selaginella tamariscina (Beauv.) Spring (TFST), and to explore the pertinent
      mechanism. MATERIALS AND METHODS: High fat diet and STZ (35 mg/kg) induced
      diabetic rats were administered with TFST at graded oral doses (100, 200 and
      400mg/kg/day, ig.) for 8 weeks. A range of parameters, including blood glucose
      and lipid, serum insulin and glucagon, glucose tolerance, were tested to evaluate
      its anti-diabetic effects. The determination of protein expression of peroxisome
      proliferator activated receptor gamma (PPAR-gamma) in adipose tissue and insulin
      receptor substrate 1 (IRS-1) in hepatic and skeletal muscle tissues was used to
      study the mechanism of TFST. Moreover, the preliminary study of TFST on the
      antioxidant activity was performed. RESULTS: The TFST possessed anti-diabetic
      activities as shown by the decreased serum levels of fast blood glucose (FBG),
      glycosylated hemoglobulin A1C (HbA1c), triglyceride (TG), total cholesterol (TC),
      free fatty acid (FFA), low density lipoprotein-cholesterol (LDL-C) and glucagon,
      as well as increased serum levels of high density lipoprotein-cholesterol (HDL
      C), insulin and C-peptide. TFST also improved the oral glucose tolerance test
      (OGTT) to a certain degree. Furthermore, TFST increased the protein expression of
      PPAR-gamma in adipose tissue, and increased the protein expressions of IRS-1 in
      hepatic and skeletal muscle tissues. These benefits were associated with
      increased superoxide dismutase (SOD) and decreased malondialdehyde (MDA) in
      serum. CONCLUSIONS: TFST exert beneficial effects on hyperglycosemia and
      hyperlipoidemia in diabetic rats possibly through regulating the levers of PPAR
      gamma in adipose tissue and IRS-1 in hepatic and skeletal muscle tissues.

PMID- 21718777
TI  - Effects of Scutellaria baicalensis on chronic cerebral hypoperfusion-induced
      memory impairments and chronic lipopolysaccharide infusion-induced memory
      impairments.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of the roots of Scutellaria baicalensis
      Georgi (Labiatae) have been widely used to relieve fever related to bacterial
      infection and inflammatory diseases in traditional Korean medicine and have been
      reported to be effective in brain diseases. These experiments were conducted to
      examine the effects of oral administration of Scutellaria baicalensis extracts on
      the rescue of memory impairments induced by chronic cerebral hypoperfusion or
      chronic lipopolysaccharide (LPS) infusion. In addition, the underlying mechanisms
      of these effects were investigated. MATERIALS AND METHODS: In the first
      experiment, chronic cerebral hypoperfusion was induced in male Wister rats by
      bilateral common carotid artery occlusion (BCCAo). Daily administration of
      Scutellaria baicalensis extracts was started on 20 day after BCCAo and given for
      40 days. A Morris water maze was then used to evaluate the status of the
      hippocampal-dependent spatial learning and hippocampal mitogen-activated protein
      kinase (MAPK) signaling was examined in control rats, rats with chronic cerebral
      hypoperfusion, and rats with chronic cerebral hypoperfusion that was administered
      Scutellaria baicalensis. In the second experiment, hippocampal microglial
      activation was induced by chronic infusions of LPS into the fourth ventricle of
      Fisher-344 rat brains. Daily administration of Scutellaria baicalensis extracts
      was started on 7 day after the surgery of LPS infusion and given for 32 days.
      Spatial memory and hippocampal microglial activation was then examined in control
      rats with an artificial cerebrospinal fluid infusion, rats with chronic LPS
      infusion, and rats with chronic LPS infusion that were administered Scutellaria
      baicalensis. RESULTS: Rats that received chronic cerebral hypoperfusion or
      chronic LPS infusion showed spatial memory impairments relative to their control
      rats; however, these symptoms were reduced by daily administration of Scutellaria
      baicalensis. Administration of Scutellaria baicalensis mitigated alterations of
      hippocampal MAPK signaling by chronic cerebral infusion and microglial activation
      by chronic LPS infusion. CONCLUSIONS: These results indicate that Scutellaria
      baicalensis may possess therapeutic potential for the prevention of Alzheimer's
      disease and vascular dementia.

PMID- 21718778
TI  - Antioxidant activities of aqueous leaf extracts of Toona sinensis on free radical
      induced endothelial cell damage.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Taiwan, Toona sinensis (Toona sinensis) is
      well known as a traditional Chinese medicine, while the underlying
      pharmacological mechanisms of this drug are still a matter of debate. MATERIALS
      AND METHODS: The purpose of this study was to evaluate the protective effects of
      non-cytotoxic concentrations of aqueous leaf extracts of Toona sinensis (TS
      extracts; 50-100 MUg/mL) and gallic acid (5 MUg/mL), a major component of these
      extracts, against AAPH-induced oxidative cell damage in human umbilical vein
      endothelial cells (ECs). RESULTS: Exposure of ECs to AAPH (15 mM) decreased cell
      viability from 100% to 43%. However, ECs were pre-incubated with TS extracts
      prior to AAPH induction resulted in increased resistance to oxidative stress and
      cell viability in a dose-dependent manner. An increase in ECs-derived PGI(2) and
      IL-1 beta in response to AAPH exposure was positively correlated with
      cytotoxicity and negatively with TS extracts concentrations. In addition, gallic
      acid also suppressed PGI(2) and IL-1 beta production in AAPH-induced ECs.
      Notably, TS extracts/gallic acid treatment significantly inhibited ROS
      generation, MDA formation, SOD/catalase activity, and Bax/Bcl-2 dysregulation in
      AAPH-stimulated ECs. Pretreatment of ECs with TS extracts/gallic acid also
      suppressed AAPH-induced cell surface expression and secretion of VCAM-1, ICAM-1
      and E-selectin, which was associated with abridged adhesion of U937 leukocytes to
      ECs. Moreover, TS extracts/gallic acid treatment significantly inhibited the AAPH
      mediated up regulation of PAI-1 and down regulation of t-PA in ECs, which may
      decrease fibrinolytic activity. CONCLUSIONS: Therefore, Toona sinensis may
      possess antioxidant properties that protect endothelial cells from oxidative
      stress. Our results also support the traditional use of Toona sinensis in the
      treatment of free radical-related diseases and atherosclerosis.

PMID- 21718779
TI  - Documentation and quantitative analysis of the local knowledge on medicinal
      plants among traditional Siddha healers in Virudhunagar district of Tamil Nadu,
      India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: India has a population with high degree of
      medical pluralism. Siddha system of Indian traditional medicine is practiced
      dominantly by the people in Tamil Nadu. The traditionally trained Siddha healers
      still play an important role in the rural health care. Their knowledge is
      comparatively more vulnerable than the documented traditional knowledge. Thus,
      the present study was aimed to document and quantitatively analyze the local
      knowledge of the traditional Siddha healers in Virudhunagar district of Tamil
      Nadu, India. MATERIALS AND METHODS: The results presented in this paper are the
      outcome of series of interviews conducted between January and August, 2010
      consisting of 196 field days. After getting prior informed consent, interviews
      were conducted and successive free-listing was used in the interviews in order to
      make informants cite the medicinal plants that they have used. By this way 96
      healers were interviewed and their data were quantitatively analyzed using
      various indices such as Informant Consensus Factor (F(ic)), Fidelity Level (FL),
      Informant Agreement on Remedies (IAR) and Cultural Importance Index (CII).
      RESULTS: This study recorded the ethno-medicinal usage of 227 species which were
      used to prepare 611 formulations for the treatment of 36 illness categories. The
      knowledge holders had the experience of minimum 20 years. There was unevenness in
      male-female ratio. Regarding the medicinal plants, easily available plants were
      holding significantly high number of citations, IAR and CII values. Nine illness
      categories had a high F(ic) value, compared to others. Species with high
      citations in these groups were Moringa oleifera (aphrodisiacs), Acalypha indica
      (dermatological ailments), Dodonaea viscosa (musculo-skeletal disorders), Solanum
      trilobatum (pulmonary ailments), Phyllanthus amarus (jaundice), Piper nigrum
      (adjuvant) Allium cepa (hemorrhoids), Azadirachta indica (antiseptic) and
      Tribulus terrestris (urinary ailments). CONCLUSION: Quantitative analysis of the
      data had revealed that the easily available species hold a high consensus and
      cultural importance. Future biomedical studies using the medicinal plants
      enumerated in this study, particularly those with high number of citations and
      high F(ic) values might yield some novel prototypes. Such studies will also be
      useful to assess the efficacy and safety of these herbal treatments to take
      decisions on the health care of rural India.

PMID- 21718780
TI  - FoxO3a immunoreactivity is markedly decreased in the dentate gyrus, not the
      hippocampus proper, of the aged gerbil.
AB  - Forkhead box O 3a (FoxO3a) has been known to link with aging process and
      senescence. In this study, we investigated the age-related changes of FoxO3a in
      the gerbil hippocampus using immunohistochemistry and western blot analysis. In
      the postnatal month 3 (PM 3) group, FoxO3a immunoreactivity was well detected in
      pyramidal cells of the hippocampus proper, and granule cells of the dentate
      gyrus. FoxO3a immunoreactivity in the pyramidal cells of the hippocampus proper
      was not changed until PM 24. However, in the dentate granule cells, FoxO3a
      immunoreactivity was much decreased in the dorsal blade, not the ventral blade,
      of the granule cell layer in the PM 6 and 12 groups compared to the PM 3 group.
      At PM 24, FoxO3a immunoreactivity in the granule cells was hardly detected.
      Western blot analysis showed that FoxO3a level was significantly decreased in the
      PM 24 group. These results indicate that FoxO3a immunoreactivity and levels are
      markedly decreased in the dentate gyrus of the aged gerbil hippocampus.

PMID- 21718781
TI  - Expression of the SNAT2 amino acid transporter during the development of rat
      cerebral cortex.
AB  - The sodium-coupled neutral amino acid transporter 2 (SNAT2) is a protein that is
      expressed ubiquitously in mammalian tissues and that displays Na(+), voltage and
      pH dependent activity. This transporter mediates the passage of small
      zwitterionic amino acids across the cell membrane and regulates the cell
      homeostasis and its volume. We have examined the expression of SNAT2 mRNA and
      protein during the development of the rat cerebral cortex, from gestation through
      the postnatal stages to adulthood. Our data reveal that SNAT2 mRNA and protein
      expression is higher during embryogenesis, while it subsequently diminishes
      during postnatal development. Moreover, during embryonic period SNAT2 colocalizes
      with the radial glial cells marker GLAST, while in postnatal period it is mainly
      detected in neuronal dendrites. These findings suggest a relevant role for amino
      acid transport through SNAT2 in the developing embryonic brain.

PMID- 21718782
TI  - Altered glucose metabolism and preserved energy charge and neuronal structures in
      the brain of mouse intermittently exposed to hypoxia.
AB  - The key for an animal to survive prolonged hypoxia is to avoid rapid decline in
      ATP levels in vital organs such as the brain. This can be well achieved by a very
      few of hypoxia-tolerant animals such as freshwater turtles and newborn animals,
      since these animals can substantially suppress their metabolic levels by
      coordinated regulation of ATP-producing and ATP-demanding pathways. However, most
      animals, especially adult mammals, can only tolerate a short period of hypoxia
      since they are unable to maintain constant ATP levels and energy charge in vital
      organs during prolonged hypoxic exposure. Here, we described a special mouse
      model, in which a hypoxia intolerant adult mouse gradually built up an ability to
      survive prolonged hypoxia after intermittent hypoxic exposures. This increased
      ability was accompanied by reductions in body temperature and O(2) consumption as
      well as transient variations in blood pCO(2), pO(2) and pH. The glucose and
      energy metabolism in the brain of the mouse altered similarly to those reported
      in the brain of hypoxic turtles. Activities of phosphofructokinase and pyruvate
      kinase, the two rate-limiting enzymes controlling the rate of glycolysis
      decreased to baseline levels after a short period of increase. In contrast, the
      activity of complex I, the major enzyme complex controlling oxidative
      phosphorylation, was kept inhibited. These alterations in the ATP-producing
      pathway suggest the occurrence of reverse Pasteur effect, indicating that the
      animal had entered a hypometabolic state favoring maintenance of ATP level and
      energy charge in hypoxic conditions. In supporting this idea, the ATP levels and
      energy charge as well as neuronal structures in the brain were well preserved.
      This study provides evidence for a possibility that a hypoxic intolerant animal
      can build up an ability to survive prolonged hypoxia through regulation of its
      glucose and energy metabolism after an appropriate hypoxic training, which
      deserves further investigation.

PMID- 21718783
TI  - An integrated approach to assessing nitroso-redox balance in systemic
      inflammation.
AB  - Most studies examining the metabolic fate of NO during systemic inflammation have
      focused on measuring the quantitatively predominating, stable anions nitrite and
      nitrate within the circulation. However, these are not necessarily the NO-related
      products that govern NO metabolism and signaling in tissues. We assessed all
      major NO derivatives temporally in blood and vital organs during inflammation and
      explored their relationship to insult severity and redox status. Male rats
      receiving intraperitoneal endotoxin or vehicle were sacrificed for organ and
      blood sampling between 0 and 24 h. Endotoxin induced transient and organ-specific
      changes in a variety of NO metabolites. Nitrite and nitrate increased, peaking at
      8 and 12 h, respectively. S- and N-nitrosation and heme-nitrosylation products
      also peaked at 8 h; these posttranslational protein modifications were associated
      with decreased myocardial function (echocardiography). Evidence of oxidative
      stress and systemic inflammation was also obtained. The rise in most NO
      derivatives was proportional to insult severity. All metabolite levels normalized
      within 24 h, despite evidence of persisting myocardial dysfunction and clinical
      unwellness. Our findings point to a complex interplay between NO production,
      antioxidant defense, and redox status. Although the precise (patho)physiologic
      roles of specific NO derivatives and their diagnostic/prognostic utility await
      further investigation, nitroso species in erythrocytes are the most sensitive
      markers of NO in systemic inflammation, detectable before clinical symptoms
      manifest.

PMID- 21718784
TI  - Muscarinic receptors stimulate cell proliferation in the human urothelium-derived
      cell line UROtsa.
AB  - The widespread non-neuronal synthesis of acetylcholine (ACh) has changed the
      paradigm of ACh acting solely as a neurotransmitter. Indeed, the presence of ACh
      in many types of proliferating cells suggests a role for this neurotransmitter in
      the control of cell division. The parasympathetic system is a major pathway
      regulating micturition, but ACh-mediated control plays a more complex role than
      previously described, acting not only in the detrusor muscle, but also
      influencing detrusor function through the activity of urothelial muscarinic
      receptors. Here we investigated the role of muscarinic receptors in mediating
      cell proliferation in the human UROtsa cell line, which is a widely used
      experimental model to study urothelium physiology and pathophysiology. Our
      results demonstrate that UROtsa cells express the machinery for ACh synthesis and
      that muscarinic receptors, with the rank order of M3>M2>M5>M1=M4, are present and
      functionally linked to their known second messengers. Indeed, the cholinergic
      receptor agonist carbachol (CCh) (1-100 MUM) concentration-dependently raised
      IP(3) levels, reaching 66+/-5% over basal. The forskolin-mediated adenylyl
      cyclase activation was reduced by CCh exposure (forskolin: 1.4+/-0.14 pmol/ml;
      forskolin+100 MUM CCh: 0.84+/-0.12 pmol/ml). CCh (1-100 MUM) concentration
      dependently increased UROtsa cell proliferation and this effect was inhibited by
      the non-selective antagonist atropine and the M(3)-selective antagonists
      darifenacin and J104129. Finally, CCh-induced cell proliferation was blocked by
      selective PI-3 kinase and ERK activation inhibitors, strongly suggesting that
      these intracellular pathways mediate, at least in part, the muscarinic receptor
      mediated cell proliferation.

PMID- 21718785
TI  - Sequence analysis of MHC class I alpha2 from sockeye salmon (Oncorhynchus nerka).
AB  - Most studies assessing adaptive MHC diversity in salmon populations have focused
      on the classical class II DAB or DAA loci, as these have been most amenable to
      single PCR amplifications due to their relatively low level of sequence
      divergence. Herein, we report the characterization of the classical class I UBA
      alpha2 locus based on collections taken throughout the species range of sockeye
      salmon (Oncorhynchus nerka). Through use of multiple lineage-specific primer
      sets, denaturing gradient gel electrophoresis and sequencing, we identified
      thirty-four alleles from three highly divergent lineages. Sequence identity
      between lineages ranged from 30.0% to 56.8% but was relatively high within
      lineages. Allelic identity within the antigen recognition site (ARS) was greater
      than for the longer sequence. Global positive selection on UBA was seen at the
      sequence level (dN:dS = 1.012) with four codons under positive selection and 12
      codons under negative selection.

PMID- 21718786
TI  - Molecular cloning, characterization and expression analysis of a miiuy croaker
      (Miichthys miiuy) CXC chemokine gene resembling the CXCL9/CXCL10/CXCL11.
AB  - Chemokines are a large family of chemotactic cytokines playing crucial roles in
      the innate immune response. In the present study, we report the cloning of a CXC
      chemokine gene resembling the closely related CXCL9/CXCL10/CXCL11 from the miiuy
      croaker Miichthys miiuy (MimiCXC). Both 5'-RACE and 3'-RACE were carried out in
      order to obtain the complete cDNA, which consists of a 73 bp 5'-UTR, a 369 bp
      open reading frame encoding 122 amino acids and a 715 bp 3'-UTR. The deduced
      MimiCXC contains a 19-aa signal peptide and a 103-aa mature polypeptide, which
      possesses the typical arrangement of four cysteines as found in other known CXC
      chemokines. It shares 4.8%-65.6% sequence identities to mammalian CXC chemokines
      and the highest sequence identity of 65.6% is between MimiCXC and CXCL10
      chemokine. Three exons and two introns were identified in MimiCXC gene. The
      MimiCXC gene was constitutively expressed in all tissues tested, although at
      different levels. Upon induction with Vibrio anguillarum, MimiCXC gene expression
      was up-regulated in kidney and spleen, however, down-regulated in liver. These
      results indicate that MimiCXC may be involved in immune responses as well as
      homeostatic processes in miiuy croaker.

PMID- 21718787
TI  - Probabilistic fibre tract analysis of cytoarchitectonically defined human
      inferior parietal lobule areas reveals similarities to macaques.
AB  - The human inferior parietal lobule (IPL) is a multimodal brain region, subdivided
      in several cytoarchitectonic areas which are involved in neural networks related
      to spatial attention, language, and higher motor processing. Tracer studies in
      macaques revealed differential connectivity patterns of IPL areas as the
      respective structural basis. Evidence for comparable differential fibre tracts of
      human IPL is lacking. Here, anatomical connectivity of five cytoarchitectonic
      human IPL areas to 64 cortical targets was investigated using probabilistic
      tractography. Connection likelihood was assessed by evaluating the number of
      traces between seed and target against the distribution of traces from that seed
      to voxels in the same distance as the target. The main fibre tract pattern
      shifted gradually from rostral to caudal IPL: Rostral areas were predominantly
      connected to somatosensory and superior parietal areas while caudal areas more
      strongly connected with auditory, anterior temporal and higher visual cortices.
      All IPL areas were strongly connected with inferior frontal, insular and
      posterior temporal areas. These results showed striking similarities with
      connectivity patterns in macaques, providing further evidence for possible
      homologies between these two species. This shift in fibre tract pattern supports
      a differential functional involvement of rostral (higher motor functions) and
      caudal IPL (spatial attention), with probable overlapping language involvement.
      The differential functional involvement of IPL areas was further supported by
      hemispheric asymmetries of connection patterns which showed left-right
      differences especially with regard to connections to sensorimotor, inferior
      frontal and temporal areas.

PMID- 21718788
TI  - Local MRI analysis approach in the diagnosis of early and prodromal Alzheimer's
      disease.
AB  - BACKGROUND: Medial temporal lobe (MTL) atrophy is one of the key biomarkers to
      detect early neurodegenerative changes in the course of Alzheimer's disease (AD).
      There is active research aimed at identifying automated methodologies able to
      extract accurate classification indexes from T1-weighted magnetic resonance
      images (MRI). Such indexes should be fit for identifying AD patients as early as
      possible. SUBJECTS: A reference group composed of 144AD patients and 189 age
      matched controls was used to train and test the procedure. It was then applied on
      a study group composed of 302 MCI subjects, 136 having progressed to clinically
      probable AD (MCI-converters) and 166 having remained stable or recovered to
      normal condition after a 24month follow-up (MCI-non converters). All subjects
      came from the ADNI database. METHODS: We sampled the brain with 7 relatively
      small volumes, mainly centered on the MTL, and 2 control regions. These volumes
      were filtered to give intensity and textural MRI-based features. Each filtered
      region was analyzed with a Random Forest (RF) classifier to extract relevant
      features, which were subsequently processed with a Support Vector Machine (SVM)
      classifier. Once a prediction model was trained and tested on the reference
      group, it was used to compute a classification index (CI) on the MCI cohort and
      to assess its accuracy in predicting AD conversion in MCI patients. The
      performance of the classification based on the features extracted by the whole 9
      volumes is compared with that derived from each single volume. All experiments
      were performed using a bootstrap sampling estimation, and classifier performance
      was cross-validated with a 20-fold paradigm. RESULTS: We identified a restricted
      set of image features correlated with the conversion to AD. It is shown that most
      information originate from a small subset of the total available features, and
      that it is enough to give a reliable assessment. We found multiple, highly
      localized image-based features which alone are responsible for the overall
      clinical diagnosis and prognosis. The classification index is able to
      discriminate Controls from AD with an Area Under Curve (AUC)=0.97 (sensitivity
      ?89% at specificity ?94%) and Controls from MCI-converters with an AUC=0.92
      (sensitivity ?89% at specificity ?80%). MCI-converters are separated from MCI-non
      converters with AUC=0.74(sensitivity ?72% at specificity ?65%). FINDINGS: The
      present automated MRI-based technique revealed a strong relationship between
      highly localized baseline-MRI features and the baseline clinical assessment. In
      addition, the classification index was also used to predict the probability of AD
      conversion within a time frame of two years. The definition of a single index
      combining local analysis of several regions can be useful to detect AD
      neurodegeneration in a typical MCI population.

PMID- 21718789
TI  - Dissociated wake-like and sleep-like electro-cortical activity during sleep.
AB  - Sleep is traditionally considered a global process involving the whole brain.
      However, recent studies have shown that sleep depth is not evenly distributed
      within the brain. Sleep disorders, such as sleepwalking, also suggest that EEG
      features of sleep and wakefulness might be simultaneously present in different
      cerebral regions. In order to probe the coexistence of dissociated (wake-like and
      sleep-like) electrophysiological behaviors within the sleeping brain, we analyzed
      intracerebral electroencephalographic activity drawn from sleep recordings of
      five patients with pharmacoresistant focal epilepsy without sleep disturbances,
      who underwent pre-surgical intracerebral electroencephalographic investigation.
      We applied spectral and wavelet transform analysis techniques to
      electroencephalographic data recorded from scalp and intracerebral electrodes
      localized within the Motor cortex (Mc) and the dorso-lateral Prefrontal cortex
      (dlPFc). The Mc showed frequent Local Activations (lasting from 5 to more than
      60s) characterized by an abrupt interruption of the sleep electroencephalographic
      slow waves pattern and by the appearance of a wake-like electroencephalographic
      high frequency pattern (alpha and/or beta rhythm). Local activations in the Mc
      were paralleled by a deepening of sleep in other regions, as expressed by the
      concomitant increase of slow waves in the dlPFc and scalp electroencephalographic
      recordings. These results suggest that human sleep can be characterized by the
      coexistence of wake-like and sleep-like electroencephalographic patterns in
      different cortical areas, supporting the hypothesis that unusual phenomena, such
      as NREM parasomnias, could result from an imbalance of these two states.

PMID- 21718790
TI  - Direct segmentation of the major white matter tracts in diffusion tensor images.
AB  - Diffusion-weighted images of the human brain are acquired more and more routinely
      in clinical research settings, yet segmenting and labeling white matter tracts in
      these images is still challenging. We present in this paper a fully automated
      method to extract many anatomical tracts at once on diffusion tensor images,
      based on a Markov random field model and anatomical priors. The approach provides
      a direct voxel labeling, models explicitly fiber crossings and can handle white
      matter lesions. Experiments on simulations and repeatability studies show
      robustness to noise and reproducibility of the algorithm, which has been made
      publicly available.

PMID- 21718792
TI  - The temporal dynamics of processing emotions from vocal, facial, and bodily
      expressions.
AB  - Face-to-face communication works multimodally. Not only do we employ vocal and
      facial expressions; body language provides valuable information as well. Here we
      focused on multimodal perception of emotion expressions, monitoring the temporal
      unfolding of the interaction of different modalities in the electroencephalogram
      (EEG). In the auditory condition, participants listened to emotional
      interjections such as "ah", while they saw mute video clips containing emotional
      body language in the visual condition. In the audiovisual condition participants
      saw video clips with matching interjections. In all three conditions, the
      emotions "anger" and "fear", as well as non-emotional stimuli were used. The N100
      amplitude was strongly reduced in the audiovisual compared to the auditory
      condition, suggesting a significant impact of visual information on early
      auditory processing. Furthermore, anger and fear expressions were distinct in the
      auditory but not the audiovisual condition. Complementing these event-related
      potential (ERP) findings, we report strong similarities in the alpha- and beta
      band in the visual and the audiovisual conditions, suggesting a strong visual
      processing component in the perception of audiovisual stimuli. Overall, our
      results show an early interaction of modalities in emotional face-to-face
      communication using complex and highly natural stimuli.

PMID- 21718791
TI  - A selective review of simulated driving studies: Combining naturalistic and
      hybrid paradigms, analysis approaches, and future directions.
AB  - Naturalistic paradigms such as movie watching or simulated driving that mimic
      closely real-world complex activities are becoming more widely used in functional
      magnetic resonance imaging (fMRI) studies both because of their ability to
      robustly stimulate brain connectivity and the availability of analysis methods
      which are able to capitalize on connectivity within and among intrinsic brain
      networks identified both during a task and in resting fMRI data. In this paper we
      review over a decade of work from our group and others on the use of simulated
      driving paradigms to study both the healthy brain as well as the effects of acute
      alcohol administration on functional connectivity during such paradigms. We
      briefly review our initial work focused on the configuration of the driving
      simulator and the analysis strategies. We then describe in more detail several
      recent studies from our group including a hybrid study examining distracted
      driving and compare resulting data with those from a separate visual oddball task
      (Fig. 6). The analysis of these data was performed primarily using a combination
      of group independent component analysis (ICA) and the general linear model (GLM)
      and in the various studies we highlight novel findings which result from an
      analysis of either 1) within-network connectivity, 2) inter-network connectivity,
      also called functional network connectivity, or 3) the degree to which the
      modulation of the various intrinsic networks were associated with the alcohol
      administration and the task context. Despite the fact that the behavioral effects
      of alcohol intoxication are relatively well known, there is still much to
      discover on how acute alcohol exposure modulates brain function in a selective
      manner, associated with behavioral alterations. Through the above studies, we
      have learned more regarding the impact of acute alcohol intoxication on
      organization of the brain's intrinsic connectivity networks during performance of
      a complex, real-world cognitive operation. Lessons learned from the above studies
      have broader applicability to designing ecologically valid, complex, functional
      MRI cognitive paradigms and incorporating pharmacologic challenges into such
      studies. Overall, the use of hybrid driving studies is a particularly promising
      area of neuroscience investigation.

PMID- 21718793
TI  - Molecular phylogeny of Cypripedium (Orchidaceae: Cypripedioideae) inferred from
      multiple nuclear and chloroplast regions.
AB  - A molecular analysis was performed on 56 taxa in the orchid genus Cypripedium
      using nrDNA ITS and five chloroplast regions (trnH-psbA, atpI-atpH, trnS-trnfM,
      trnL-F spacer, and the trnL intron). The genus Cypripedium was confirmed as
      monophyletic. Our data provided strong support for monophyletic grouping of eight
      infrageneric sections (Subtropica, Obtusipetala, Trigonopedia, Sinopedilum,
      Bifolia, Flabelinervia, Arietinum, and Cypripedium) defined in earlier taxonomic
      treatments, and paraphyletic grouping of two sections (Irapeana and Retinervi).
      Within the genus Cypripedium, the first divergent lineage consisted of two
      Mesomaerican species, and subsequently the Cypripedium debile lineage from
      eastern Asia was split. Our study did not support the notion that two Asian
      species (Cypripedium subtropicum and Cypripedium singchii) were closely related
      to either Mesoamerican Cypripedium irapeanum or North American Cypripedium
      californicum, as indicated by previous interpretations based on morphological
      evidences. In addition, one pair of vicariant species, Cypripedium plectrochilum
      (eastern Asia) and Cypripedium arietinum (North America), unique to section
      Arietinum, was confirmed. Furthermore, within the monophyletic section
      Cypripedium two previously recognized subsections, Cypripedium and Macrantha,
      were shown to be paraphyletic. Our results suggested that this section split into
      two groups based on distribution (North America vs. Eurasia) instead of such
      previously used, morphological traits as flower color, and the shape of the lips
      (labellum) and lateral petals.

PMID- 21718794
TI  - Microbial challenges of poultry meat production.
AB  - Food safety and shelf-life are both important microbial concerns in relation to
      broiler meat production. Focus is mainly placed on the absence or control of
      potentially pathogenic microbes such as Salmonella spp. and Campylobacter spp.
      but, from the commercial point of view, other spoilage bacteria also play a role
      as potential threats. Regarding food safety, the primary target should be the
      production of pathogen-free live animals, thus allowing slaughter plants to keep
      the processing line free of those microorganisms. Consumers believe that quality
      of foods from organic production is superior to foods from conventional
      production. The aim of the present study was to evaluate and compare the
      bacterial quality of chicken meat from organic and conventional production on the
      basis of traditional meat quality criteria. Fresh free grazing broiler carcasses
      were purchased directly from rural households (n = 80) and fresh retail chicken
      parts from conventional broiler carcasses from the local supermarkets in the
      region of Epirus (Poultry Producers Association. Arta) (n = 200). The samples
      were microbiologically tested for the presence of bacteria such as: Salmonella
      spp., Listeria monocytogenes, Staphylococcus aureus, Enterobacteriaceae,
      Escherichia coli, Campylobacter spp., and C. perfringens. Total count of aerobic
      mesophilic bacteria was also determined. Bacteriological tests were performed by
      means of standard methods of isolation and identification of individual species
      of bacteria according to ISO requirements. API-tests (bioMerieux) and Vitek 2
      Identification System (bioMerieux) were used for biochemical determination. High
      levels of microbial contamination and occurrence of pathogenic bacteria at then
      fresh free grazing broiler carcasses reflect the poor hygienic quality of the
      slaughter conditions in the rural households.

PMID- 21718795
TI  - Suppression of lung cancer cell invasion and metastasis by connexin43 involves
      the secretion of follistatin-like 1 mediated via histone acetylation.
AB  - Although connexin has been recognized as a tumor suppressor in many types of
      cancer, the underlying mechanisms are poorly understood. We have previously shown
      that transfection of connexin43 (Cx43) cDNA retarded the growth of a highly
      metastatic human pulmonary giant cell carcinoma cell line, PG, both in vitro and
      in vivo. Here, we further demonstrate that the metastasis and invasion, but not
      the migration, of PG cells are also inhibited following Cx43 transfection. The
      diminishment of metastasis and invasion is associated with down-regulation of
      genes including MMP-2, S100A, LAMA4, and HDAC10, as well as up-regulation of
      genes such as MTSS1 and FSTL1 as revealed by gene chip analysis. Interestingly,
      the suppression effects of Cx43 are related to secreted factor(s), which are
      blocked by FSTL1 antibody treatment in a dose-dependent manner. Furthermore, the
      FSTL1 promoter was shown to be associated with acetylated histones H3 and H4 upon
      Cx43 transfection. These data suggest that Cx43 inhibits the invasion and
      metastasis of PG cells by modulating the secretion of FSTL1, which is regulated
      by histone acetylation. Cx43 may act as a "histone deacetylase inhibitor" to
      modulate gene expression and subsequent cellular functions in PG cells.

PMID- 21718796
TI  - Human cardiac fibroblasts express ICAM-1, E-selectin and CXC chemokines in
      response to proinflammatory cytokine stimulation.
AB  - Neutrophil attraction and adhesion to endothelial cells occurs via well defined
      mechanisms, yet the ability of other cell types to express neutrophil-binding
      adhesion molecules is not well studied. Cardiac fibroblasts (CF) are a key cell
      type involved in repair of the infarcted myocardium, a scenario in which
      neutrophil recruitment is perceived to be detrimental. Here we determined the
      effects of proinflammatory cytokines on expression of neutrophil-binding adhesion
      molecules and neutrophil-attracting chemokines in CF cultured from multiple
      patients, and explored the underlying regulatory mechanisms. An adhesion molecule
      focused RT-PCR array identified 5 transcripts that were increased markedly in
      human CF treated with the proinflammatory cytokine interleukin-1 (IL-1, 10 ng/ml,
      6 h); including intercellular cell adhesion molecule (ICAM-1) and E-selectin.
      Real-time RT-PCR verified the array data and immunoblotting confirmed cytokine
      induced ICAM-1 and E-selectin protein expression. Treatment with a panel of
      pharmacological inhibitors identified the NF-kappaB pathway as mediating IL-1
      induced ICAM-1 and E-selectin mRNA and protein expression. Additionally, E
      selectin expression in human CF was markedly potentiated by the JNK inhibitor
      SP600125, but this was not observed when a more selective inhibitor ((L)-JNKI-1)
      was used, or in human vascular endothelial cells. IL-1 also stimulated CF to
      secrete the neutrophil chemoattractant CXCL8 via a p38- and NF-kappaB-dependent
      mechanism, as well as inducing CXCL1, CXCL2 and CXCL5 mRNA expression. In
      conclusion, human CF express neutrophil-binding adhesion molecules and neutrophil
      chemoattractants in response to proinflammatory cytokines suggesting that, in
      addition to EC, CF may play an important role in regulating neutrophil
      recruitment into the infarcted myocardium.

PMID- 21718798
TI  - Specific serum IgG, but not IgA, antibody against purified Opisthorchis viverrini
      antigen associated with hepatobiliary disease and cholangiocarcinoma.
AB  - Opisthorchiasis caused by Opisthorchis viverrini infection induces hepatobiliary
      disease (HBD)-associated cholangiocarcinoma (CCA) via a chronic inflammatory
      immune response. Here, we evaluated specific IgG and IgA antibodies against
      different fractions of O. viverrini antigen in residents from an endemic
      community in Northeast Thailand with varying hepatobiliary abnormalities. Crude
      somatic O. viverrini antigen was purified into three fractions (viz., P1, P2 and
      P3) by gel infiltration chromatography and these served as antigens for detection
      of fluke-specific IgG and IgA antibodies by enzyme-linked immunosorbent assay
      (ELISA). The results revealed fluke-specific IgG and IgA antibody levels-against
      these antigens from subjects with O. viverrini-positive HBD-higher than in
      subjects with O. viverrini-negative HBD. Interestingly, the rank of fluke
      specific IgG (and not IgA) antibody levels against crude extract and P1 antigens
      was CCA>severe HBD>mild HBD>healthy individuals. Purified antigens reduced cross
      reactivity with other parasites compared to the crude antigen. Multiple linear
      regression analysis showed that HBD status was significantly associated with the
      liver fluke-specific IgG antibody against purified antigens. These results
      suggest that purified O. viverrini-antigen improves serodiagnosis for the
      evaluation of opisthorchiasis-associated HBD, and may be useful in the screening
      of opisthorchiasis in subjects at risk of developing CCA.

PMID- 21718799
TI  - Egg formation and the early embryonic development of Aspidogaster limacoides
      Diesing, 1835 (Aspidogastrea: Aspidogastridae), with comments on their
      phylogenetic significance.
AB  - Ultrastructural aspects of the early embryonic development of the aspidogastrean
      Aspidogaster limacoides are described and their phylogenetic implications
      discussed. Whereas the proximal regions of the uterine lumen usually contain
      unembryonated eggs or eggs with early embryos, the posterior or distal regions of
      the uterus are filled with eggs containing a fully-developed cotylocidium. The
      eggs of A. limacoides can be classified as polylecithal due to the presence of
      numerous vitellocytes which accompany each fertilized oocyte or ovum during egg
      formation. The results of the study are described in details under six headings:
      (1) general characteristics of the intrauterine eggs; (2) eggshell and operculum
      formation; (3) unembryonated eggs; (4) zygote formation and early cleavage
      divisions; (5) embryonic envelope formation; and (6) early degeneration or
      apoptosis of some blastomeres. The late differentiation of the operculum,
      possible functions of GER-bodies, and the early degeneration of vitellocytes and
      some blastomeres in this species are compared, drawn and discussed with
      corresponding observations reported for other parasitic Platyhelminthes. The most
      important differences are apparent in the number of egg envelopes and their mode
      of formation in A. limacoides compared with previous reports for both digeneans
      and cestodes. The results of the present TEM study indicate that the three
      macromeres, resulting from two cleavage divisions, take part in the formation of
      a single embryonic outer envelope in A. limacoides, and that this takes place at
      a very early stage of embryogenesis. Their fusion results in the formation of a
      single continuous cytoplasmic layer surrounding the early embryo, which is
      composed of only a small number of undifferentiated blastomeres. The early
      separation of the macromeres may indicate an equal cleavage pattern. These
      results suggest that the systematic position of the Aspidogastrea among the
      Platyhelminthes still remains somewhat equivocal, and indicate the need for more
      studies on the embryonic development, larval morphogenesis and molecular
      phylogeny for the elucidation of the relationships between this enigmatic group
      and related taxa.

PMID- 21718800
TI  - The liver fluke Opisthorchis viverrini expresses nitric oxide synthase but not
      gelatinases.
AB  - Host-parasite interaction during infection with the liver fluke Opisthorchis
      viverrini plays an important role in opisthorchiasis-associated
      cholangiocarcinoma via nitric oxide (NO) production. Host cells induce nitric
      oxide synthase (NOS)-dependent DNA damage and secrete Ras-related C3 botulinum
      toxin substrate (Rac)1, heme oxygenase (HO)-1, and gelatinases (matrix
      metalloproteinase (MMP)2 and MMP9). We evaluated whether these enzymes are
      expressed in O. viverrini. Colocalization of NOS and Rac1 was most prominently
      detected on day 30 post-infection (p.i.) in the gut, reproductive organ, eggs,
      acetabular and tegument. Expression of HO-1, an antioxidative enzyme, increased
      in a similar pattern to NOS, but was not present in the tegument. The levels of
      nitrate/nitrite, end products of NO, and ferric reducing antioxidant capacity, an
      indicator of antioxidant enzyme capacity, in parasite homogenates were highest on
      day 30 p.i. and then decreased on day 90 p.i. In contrast, zymography revealed
      that MMP2 and MMP9 were not present in parasite homogenates at all time points.
      In conclusion, O. viverrini induces NOS expression and NO production, but does
      not express gelatinases. The study may provide basic information and an insight
      into drug design for prevention and/or intervention approaches against O.
      viverrini infection.

PMID- 21718801
TI  - Mechanisms involved in the intestinal absorption of dietary vitamin A and
      provitamin A carotenoids.
AB  - Vitamin A is an essential nutrient for humans and is converted to the visual
      chromophore, 11-cis-retinal, and to the hormone, retinoic acid. Vitamin A in
      animal-derived foods is found as long chain acyl esters of retinol and these are
      digested to free fatty acids and retinol before uptake by the intestinal mucosal
      cell. The retinol is then reesterified to retinyl esters for incorporation into
      chlylomicrons and absorbed via the lymphatics or effluxed into the portal
      circulation facilitated by the lipid transporter, ABCA1. Provitamin A carotenoids
      such as beta-carotene are found in plant-derived foods. These and other
      carotenoids are transported into the mucosal cell by scavenger receptor class B
      type I (SR-BI). Provitamin A carotenoids are partly converted to retinol by
      oxygenase and reductase enzymes and the retinol so produced is available for
      absorption via the two pathways described above. The efficiency of vitamin A and
      carotenoid intestinal absorption is determined by the regulation of a number of
      proteins involved in the process. Polymorphisms in genes for these proteins lead
      to individual variability in the metabolism and transport of vitamin A and
      carotenoids. This article is part of a Special Issue entitled Retinoid and Lipid
      Metabolism.

PMID- 21718802
TI  - Analysis of oxysterol metabolomes.
AB  - Oxysterols are oxygenated forms of cholesterol. This definition can, however, be
      expanded to include oxygenated derivatives of plant sterols and also of
      cholesterol precursors. Oxysterols are formed in the first steps of cholesterol
      metabolism and also from cholesterol by reactive oxygen species. Oxysterols were
      once thought of as simple intermediates, or side-products, in the conversion of
      cholesterol to hormonal steroids and bile acids, however, they have subsequently
      been shown to be biologically active molecules in their own right. In this
      article we will discuss methods of oxysterol analysis including "classical" gas
      chromatography-mass spectrometry (GC-MS) methods and more recent liquid
      chromatography (LC)-MS methods. Our main focus, however, will be on analytical
      methods based on "charge-tagging" and LC-tandem mass spectrometry (MS/MS or
      MS(n)) which we have developed over the last decade in our laboratory. Examples
      will be given of oxysterol analysis in brain, cerebrospinal fluid (CSF) and
      blood. The advantages and disadvantages of the various methods of oxysterol
      analysis will be discussed.

PMID- 21718803
TI  - A novel protocol to develop a prediction model that identifies patients with
      nerve-related neck and arm pain who benefit from the early introduction of neural
      tissue management.
AB  - Researchers have been encouraged to identify characteristics that predict
      patients' responses to different musculoskeletal interventions. We describe a
      novel protocol to develop a prediction model that identifies patients with nerve
      related neck and arm pain who are likely to benefit from the early introduction
      of neural tissue management (NTM). Prediction models for musculoskeletal
      treatments have usually been developed by analyzing single group study data with
      standard logistic regression. However, this approach has important limitations
      and our two step process for model development will address these limitations.
      Eligible patients will be aged 18 to 60 years with a minimum four week episode of
      non-traumatic neck and unilateral arm pain that is reproduced by a mechanical
      provocation test for the cervical nerve roots and median nerve. The outcome being
      predicted by the model is patient-reported improvement four weeks after baseline.
      Patients rating themselves at least 'moderately better' on a Global Rating of
      Change scale will be considered 'improved'. First, a randomized control trial
      (RCT) comparing standardized NTM to advice to remain active will determine
      whether this outcome represents a NTM treatment effect. The RCT has 80% power to
      detect a number needed to treat <= 3 favoring NTM (p <= 0.05). Second, a
      comprehensive set of examination items will be analyzed with penalized logistic
      regression to select the best items for the prediction model.

PMID- 21718804
TI  - The Infant Fish Oil Supplementation Study (IFOS): design and research protocol of
      a double-blind, randomised controlled n--3 LCPUFA intervention trial in term
      infants.
AB  - STUDY DESIGN: The Infant Fish Oil Supplementation Study is a double-blind
      randomised controlled trial investigating whether the incidence of allergic
      disease can be reduced and developmental outcomes enhanced through
      supplementation with omega-3 fatty acids. Infants at high risk of developing
      allergic disease will be randomised to receive either fish oil or olive oil
      supplements until 6 months of age and followed up at six postnatal clinic visits
      to assess allergy outcomes and infant neurodevelopment. INTERVENTION: Study
      groups to consist of a treatment group allocated to receive 650 mg of fish oil
      daily (250-280 mg docosahexaenoic acid and at least 60 mg eicosapentaenoic acid
      and a placebo group (olive oil) from birth to 6 months of age. OUTCOMES: Allergy
      outcomes will be assessed by clinical history, clinical assessments and allergen
      skin prick tests at the 12, 30 and 60 month visits. Neurodevelopmental
      assessments to be conducted at 18 months, and language questionnaires at 12, 18
      and 30 months. Samples will be collected from mothers antenatally, from infants
      at birth, and at clinic visits from 6 months onwards for immunological
      assessments. Fatty acid composition to be measured in erythrocytes and plasma (at
      birth and after the supplementation period) to assess the effect of the
      intervention on fatty acid status. Information on medical history, diet and other
      lifestyle factors at an antenatal clinic visit and postnatal clinic visits will
      also be collected. CONCLUSION: This study is designed to examine clinically
      relevant effects of a novel, non-invasive and potentially low cost approach to
      reduce the incidence of allergic disease and facilitate neurodevelopment during
      early childhood.

PMID- 21718805
TI  - Conspicuous multidrug-resistant Mycobacterium tuberculosis cluster strains do not
      trespass country borders in Latin America and Spain.
AB  - Multidrug-resistant Mycobacterium tuberculosis strain diversity in Ibero-America
      was examined by comparing extant genotype collections in national or state
      tuberculosis networks. To this end, genotypes from over 1000 patients with
      multidrug-resistant tuberculosis diagnosed from 2004 through 2008 in Argentina,
      Brazil, Chile, Colombia, Venezuela and Spain were compared in a database
      constructed ad hoc. Most of the 116 clusters identified by IS6110 restriction
      fragment length polymorphism were small and restricted to individual countries.
      The three largest clusters, of 116, 49 and 25 patients, were found in Argentina
      and corresponded to previously documented locally-epidemic strains. Only 13 small
      clusters involved more than one country, altogether accounting for 41 patients,
      of whom 13 were, in turn, immigrants from Latin American countries different from
      those participating in the study (Peru, Ecuador and Bolivia). Most of these
      international clusters belonged either to the emerging RD(Rio) LAM lineage or to
      the Haarlem family of M. tuberculosis and four were further split by country when
      analyzed with spoligotyping and rifampin resistance-conferring mutations,
      suggesting that they did not represent ongoing transnational transmission events.
      The Beijing genotype accounted for 1.3% and 10.2% of patients with multidrug
      resistant tuberculosis in Latin America and Spain, respectively, including one
      international cluster of two cases. In brief, Euro-American genotypes were widely
      predominant among multidrug-resistant M. tuberculosis strains in Ibero-America,
      reflecting closely their predominance in the general M. tuberculosis population
      in the region, and no evidence was found of acknowledged outbreak strains
      trespassing country borders.

PMID- 21718806
TI  - Preparation and functional identification of a monoclonal antibody against the
      recombinant soluble human NKp30 receptor.
AB  - NKp30 is an important activating receptor of human natural killer (NK) cells that
      participates in NK cell activation and cytotoxicity against tumor and infected
      cells. To study the function of NKp30, anti-human NKp30 monoclonal antibody was
      prepared. The human NKp30 ectodomain (rhNKp30) was expressed in Escherichia coli
      as inclusion bodies and refolded using the dilution method. The refolded rhNKp30
      was purified by immobilized metal affinity chromatography. The activity of
      soluble rhNKp30 was confirmed by flow cytometry and NK cytotoxicity assays. Four
      hybridoma cell lines producing monoclonal antibodies against rhNKp30 were
      obtained. One of the monoclonal antibodies, designated as "3G5", was highly
      specific and could be used in western blotting, immunoprecipitation, ELISA, and
      flow cytometry assays. The preparation of soluble rhNKp30 and a monoclonal
      antibody against NKp30 may provide useful tools for further functional studies of
      human NKp30.

PMID- 21718807
TI  - Antibodies against acute phase proteins and their functions in the pathogenesis
      of disease: a collective profile of 25 different antibodies.
AB  - The acute phase response is a defense system in which the innate immune response
      is activated following injury or infection. Positive and negative acute phase
      proteins (APPs) are crucial for protecting the host organism, as well as
      returning it to homeostatic levels, the first with elevated concentrations and
      the latter with decreased concentrations during the acute phase. Reports about
      the presence of antibodies against APPs are known, however their individual, as
      well as potentially collective, pathological or physiological roles are still
      emerging. Some of these autoantibodies are specifically connected with diseases
      (such as pancreatic secretory trypsin inhibitor and C3, C4 nephritic factors),
      while others have been reported as natural antibodies. The persistent presence
      (even if only minor) of autoantibodies in healthy blood donors indicates an
      overlapping category of autoantibodies, which could become pathogenic, depending
      on the autoantibody characteristics such as avidity, epitope specificity, changes
      in the microenvironment leading to different oxidative status and others. This
      review uses the novel approach of studying the overall autoantibody population
      against APPs, their functions and connections to diseases. The primary function
      of autoantibodies against APPs (anti-APPs) is thought to promote their clearance,
      however autoantibodies against negative APPs have also been found and applying
      the same role to those is doubtful. There is also the theory of consumption in
      the stage of inflammation, which could be relevant to anti-APPs. Reports about
      protective roles of autoantibodies are also emerging, showing lowered levels of
      antibodies in diseases, which could be interesting for therapeutic intervention.

PMID- 21718808
TI  - Control of human inspiratory motoneurones during voluntary and involuntary
      contractions.
AB  - In this review, we consider the discharge of human respiratory motoneurones
      during involuntary and voluntary contractions and what this reveals about the
      neural control of respiratory muscles. Motoneurone discharge is the final output
      of neural drive and can be recorded in humans during a range of experimental
      protocols. However, human studies have limitations and recordings can only be
      made indirectly from motoneurones. Animal data allows us to hypothesise how
      neural drive to these motoneurones is organised in humans. We propose that
      premotoneuronal networks, perhaps in the spinal cord (i.e. 'spinal distribution
      networks'), sculpt descending drive from multiple sources. This would determine
      the differential pattern of activation across inspiratory muscles, preserve the
      neural and mechanical coupling when voluntary breaths are taken and allow for
      different patterns of activation in non-respiratory contractions.

PMID- 21718809
TI  - Influence of temperature, pH and dissolved oxygen concentration on enhanced
      biological phosphorus removal under strictly aerobic conditions.
AB  - Previous research has suggested that enhanced biological phosphorus removal
      (EBPR) from wastewater can be achieved under continuous aerobic conditions over
      the short term. However, little is known how environmental conditions might
      affect aerobic EBPR performance. Consequently we have investigated the impact of
      temperature, pH and dissolved oxygen (DO) concentrations on EBPR performance
      under strictly aerobic conditions. A sequencing batch reactor (SBR) was operated
      for 108 days on a six-hour cycle (four cycles a day). The SBR ran under
      alternating anaerobic-aerobic conditions as standard and then operated under
      strictly aerobic conditions for one cycle every three or four days. SBR
      operational temperature (10, 15, 20, 25 and 30 degrees C), pH (6, 7, 8 and 9) and
      DO concentration (0.5, 2.0 and 3.5mg/L) were changed consecutively during the
      aerobic cycle. Recorded increases in mixed liquor phosphorus (P) concentrations
      during aerobic carbon source uptake (P release) were affected by the biomass P
      content rather than the imposed changes in the operational conditions. Thus, P
      release levels increased with biomass P content. By contrast, subsequent aerobic
      P assimilation (P uptake) levels were both affected by changes in operational
      temperature and pH, and peaked at 20-25 degrees C and pH 7-8. Highest P uptake
      detected under these SBR operating conditions was 15.4 mg Pg-MLSS(-1) (at 25
      degrees C, pH 7 and DO 2.0mg/L). The ability of the community for linked aerobic
      P release and P uptake required the presence of acetate in the medium, a finding
      which differs from previous data, where these are reported to occur in the
      absence of any exogenous carbon source. Fluorescence in situ hybridization was
      performed on samples collected from the SBR, and Candidatus 'Accumulibacter
      phosphatis' cells were detected with PAOmix probes through the operational
      periods. Thus, Candidatus 'Accumulibacter phosphatis' seemed to perform P removal
      in the SBR as shown in previous studies on P removal under strictly aerobic
      conditions.

PMID- 21718810
TI  - Effect of 2,4,6-trichlorophenol on the microbial activity of adapted anaerobic
      granular sludge bioaugmented with Desulfitobacterium strains.
AB  - The anaerobic degradation of 2,4,6-trichlorophenol (246TCP) has been studied in
      batch experiments. Granular sludges previously acclimated to 2,4-dichlorophenol
      (24DCP) and then adapted to at a load of 330 MUM 246TCPd(-1) in two expanded
      granular sludge bed (EGSB) reactors were used. One of the reactors had been
      bioaugmented with Desulfitobacterium strains whereas the other served as control.
      246TCP was tested at concentrations between 250 and 760 MUM. The study focused on
      the fate of both fermentation products and chlorophenols derived from
      dechlorination of 246TCP. This compound mainly affected the biodegradation of
      acetate and propionate, which were inhibited at 246TCP concentrations above 380
      MUM. Lactate and ethanol were also accumulated at 760 MUM 246TCP. Methanogenesis
      was strongly inhibited at 246TCP concentrations higher than 380 MUM. A diauxic
      production of methane was observed, which can be described by a kinetic model in
      which acetoclastic methanogenesis was inhibited, whereas hydrogenotrophic
      methanogenesis was hardly affected by 246TCP. The similarity of the kinetic
      parameters obtained for the control and the bioaugmented sludges (K(i)=175-200
      MUM 246TCP and n=7) suggests that methanogenesis is not affected by the
      bioaugmentation. Moreover, the 246TCP dechlorination occurred mainly at ortho
      position, successively generating 24DCP and 4-chlorophenol (4CP), which was
      identified as final product. The bioaugmentation does not significantly improve
      the anaerobic biodegradation of 246TCP. It has been shown that the active biomass
      is capable of bioaccumulating 246TCP and products from dechlorination, which are
      subsequently excreted to the bulk medium when the biomass becomes active again. A
      kinetic model is proposed which simultaneously explains 246TCP and 24DCP
      reductive dechlorinations and includes the 246TCP bioaccumulation. The values of
      the kinetic parameters for 246TCP dechlorination were not affected by
      bioaugmentation (V(max)=5.3 and 5.1 MUM h(-1) and K(s)=5.8 and 13.1 MUM for
      control and bioaugmented sludges, respectively).

PMID- 21718811
TI  - Biotransformation of the organochlorine pesticide trans-chlordane by wood-rot
      fungi.
AB  - There is very limited information on the biotransformation of organochlorine
      pesticide chlordane by microorganisms, and no systematic study on the metabolic
      products and pathways for chlordane transformation by wood-rot fungi has been
      conducted. In this study, trans-chlordane was metabolized with the wood-rot fungi
      species Phlebia lindtneri, Phlebia brevispora and Phlebia aurea, which are
      capable of degrading polychlorinated dibenzo-p-dioxin and heptachlor epoxide. At
      the end of 42 days of incubation, over 50% of trans-chlordane was degraded by the
      fungal treatments in pure cultures. These fungi transformed trans-chlordane to at
      least eleven metabolites including a large amount of hydroxylated products such
      as 3-hydroxychlordane, chlordene chlorohydrin, heptachlor diol,
      monohydroxychlordene and dihydroxychlordene. P. lindtneri particularly can
      metabolize oxychlordane, a recalcitrant epoxide product of chlordane, into a
      hydroxylated product through substitution of chlorine atom by hydroxyl group. The
      present results suggest that hydroxylation reactions play an important role in
      the metabolism of trans-chlordane by these Phlebia species. Additionally,
      transformation of trans-chlordane and production of hydroxylated metabolites were
      efficiently inhibited by the addition of cytochrome P450 inhibitors, piperonyl
      butoxide and 1-aminobenzotriazole, demonstrating that fungal cytochrome P450
      enzymes are involved in some steps of trans-chlordane metabolism, particularly in
      the hydroxylation process.

PMID- 21718812
TI  - Granular activated carbon based microbial fuel cell for simultaneous
      decolorization of real dye wastewater and electricity generation.
AB  - Decolorization of dye wastewater before discharge is pivotal because of its
      immense color and toxicities. In this study, a granular activated carbon based
      microbial fuel cell (GACB-MFC) was used without using any expensive materials
      like Nafion membrane and platinum catalyst for simultaneous decolorization of
      real dye wastewater and bioelectricity generation. After 48 hours of GACB-MFC
      operation, 73% color was removed at anode and 77% color was removed at cathode.
      COD removal was 71% at the anode and 76% at the cathode after 48 hours. Toxicity
      measurements showed that cathode effluent was almost nontoxic after 24 hours. The
      anode effluent was threefold less toxic compared to original dye wastewater after
      48 hours. The GACB-MFC produced a power density of 1.7 W/m(3) with an open
      circuit voltage 0.45 V. One of the advantages of the GACB-MFC system is that pH
      was automatically adjusted from 12.4 to 7.2 and 8.0 at the anode and cathode
      during 48 hours operation.

PMID- 21718813
TI  - IPM: An integrated protein model for false discovery rate estimation and
      identification in high-throughput proteomics.
AB  - In high-throughput mass spectrometry proteomics, peptides and proteins are not
      simply identified as present or not present in a sample, rather the
      identifications are associated with differing levels of confidence. The false
      discovery rate (FDR) has emerged as an accepted means for measuring the
      confidence associated with identifications. We have developed the Systematic
      Protein Investigative Research Environment (SPIRE) for the purpose of integrating
      the best available proteomics methods. Two successful approaches to estimating
      the FDR for MS protein identifications are the MAYU and our current SPIRE
      methods. We present here a method to combine these two approaches to estimating
      the FDR for MS protein identifications into an integrated protein model (IPM). We
      illustrate the high quality performance of this IPM approach through testing on
      two large publicly available proteomics datasets. MAYU and SPIRE show remarkable
      consistency in identifying proteins in these datasets. Still, IPM results in a
      more robust FDR estimation approach and additional identifications, particularly
      among low abundance proteins. IPM is now implemented as a part of the SPIRE
      system.

PMID- 21718814
TI  - Oxidative stress, inflamm-aging and immunosenescence.
AB  - Immunosenescence is characterized by a decreased ability of the immune system to
      respond to foreign antigens, as well as a decreased ability to maintain tolerance
      to self-antigens. This results in an increased susceptibility to infection and
      cancer and reduced responses to vaccination [1-5]. The mechanisms underlying
      immunosenescence comprise a series of cellular and molecular events involving
      alteration of several biochemical pathways and different cellular populations,
      and for the most part our understanding of these molecular mechanisms is still
      fragmentary. In this review we will focus on the process of senescence associated
      with oxidative stress, in particular how protein oxidation alters the
      functionality of immune cells and how oxidative stress contributes to a chronic
      inflammatory process often referred as inflamm-aging.

PMID- 21718815
TI  - Identification and characterization of the major alternative promoter regulating
      Bcrp1/Abcg2 expression in the mouse intestine.
AB  - Mouse models are often used to predict drug absorption in humans. Mouse Bcrp1
      protein exhibits sequence and functional homology with human BCRP protein.
      Additionally, BCRP/Bcrp1 expression is regulated by alternative promoter usage in
      humans and mice; however, the precise intestine-specific alternative promoter
      utilized in either species is yet to be determined. Therefore we sought to
      identify and characterize the mouse intestinal Bcrp1 promoter. Using real-time
      quantitative RT-PCR and 5' RACE PCR we first established the predominance of a
      single Bcrp1 first exon (E1b) in the Bcrp1 mRNA isolated throughout the mouse
      intestine. Simultaneously using 5' RACE PCR we identified E1C as the predominant
      BCRP 5' UTR expressed in the human intestine. Next we established functional
      activity for the murine promoter upstream of E1b using reporter assays.
      Subsequently using deletion-construct analysis we found the core promoter region
      to span -231 to -42bps from the transcriptional start site of E1b. We then
      predicted a cAMP response element (CRE) as a transcription factor binding site
      unique only to the E1b promoter region, using in silico methods. We finally
      established functional interaction of phospho-CREB (p-CREB) protein with the CRE
      on the E1b promoter using both functional assays and chromatin
      immunoprecipitation assays. In conclusion, mouse intestinal Bcrp1 expression is
      regulated by a single alternative promoter upstream of E1b, the predominant Bcrp1
      mRNA isoform expressed in the mouse intestine. Furthermore, Bcrp1 E1b mRNA
      expression is regulated by binding of p-CREB to its cis site on the mouse E1b
      promoter region.

PMID- 21718816
TI  - The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone
      resorption and vesicular trafficking.
AB  - Odanacatib (ODN) is a selective, potent and reversible inhibitor of cathepsin K
      (CatK) that inhibits bone loss in postmenopausal osteoporosis. Evidence from
      osteoclast (OC) formation from bone marrow of CatK(-/-) mice or human OC
      progenitors treated with ODN, demonstrated that CatK inhibition has no effect on
      osteoclastogenesis or survival of OCs. Although having no impact on OC
      activation, ODN reduces resorption activity as measured by CTx release
      (IC(50)=9.4 nM) or resorption area (IC(50)=6.5 nM). While untreated cells
      generate deep trail-like resorption lacunae, treated OCs form small discrete
      shallow pits. ODN leads to significant accumulation of intracellular vesicles
      intensely stained for CatK and TRAP. CatK (+) vesicles localize toward the
      basolateral and functional secretory membranes of the polarized OC and TRAP(+)
      vesicles evenly distribute in the cytoplasm, suggesting that ODN disrupts
      multiple vesicular trafficking pathways. Intracellular levels of both precursor
      and mature TRAP were increased by 2-fold and the pre-pro and mature CatK by 6-
      and 2-fold in ODN-treated OCs compared to untreated controls. ODN treated OC
      accumulates labeled degraded bone matrix proteins in CatK containing vesicles. In
      summary, ODN treatment inhibits bone resorption by blocking degradation of
      demineralized collagen in the resorption lacunae, and retarding transcytosis for
      further processing of degraded proteins.

PMID- 21718817
TI  - Biventricular continuous flow VADs demonstrate diurnal flow variation and lead to
      end-organ recovery.
AB  - HeartWare continuous flow ventricular assist devices (HVAD) configured as
      biventricular assist devices maintain diurnal flow variation, lead to end-organ
      recovery, and provide for a successful bridge-to-heart transplantation in the
      first successful North American use of continuous flow biventricular assist
      devices.

PMID- 21718818
TI  - Surgical resection of locally advanced pulmonary adenocarcinoma after gefitinib
      therapy.
AB  - First-line therapy with gefitinib prolongs progression-free survival and improves
      quality of life among selected patients with non-small cell lung cancer. Selected
      locally advanced patients may derive benefit from surgical resection after
      gefitinib therapy. Further clinical trials are needed to evaluate the role of
      gefitinib therapy followed by surgical resection.

PMID- 21718819
TI  - Solitary nasopharyngeal metastasis from lung primary: a long-term survivor after
      radiotherapy.
AB  - Isolated nasopharyngeal metastasis from lung primary is a rare condition. We
      report a patient with stage 1B adenocarcinoma of the lung who underwent
      anatomical lung resection and was subsequently found to have solitary
      nasopharyngeal metastasis. The patient received radiotherapy to nasopharynx and
      remained disease-free for 10 years from the date of diagnosis of nasopharyngeal
      metastasis. We postulate that solitary nasopharyngeal metastasis from lung
      primary might be a separate entity that responded well to radiotherapy.

PMID- 21718820
TI  - Inflammatory myofibroblastic tumor invading pulmonary trunk with multiple
      mediastinal lymph node metastasis.

PMID- 21718821
TI  - The use of veritas collagen matrix to reconstruct the posterior chest wall after
      costovertebrectomy.
AB  - Among the new materials introduced for chest wall reconstruction, the use of
      collagen matrix is gaining increasing favor for its biomechanical properties. We
      describe the reconstruction of the chest wall with Veritas (Synovis, St Paul, MN)
      collagen matrix of a posterior chest wall defect after costovertebrectomy for
      Ewing's sarcoma. En bloc resection was performed, including partial D7 through D9
      vertebrectomy along with the posterolateral segments of corresponding ribs. The
      collagen matrix patch was sutured to the spine stabilizer and the surrounding rib
      segments and was covered by previously raised latissimus dorsi and trapezius
      muscle flaps. Excellent stabilization was obtained.

PMID- 21718822
TI  - Thrombocytapheresis: managing essential thrombocythemia in a surgical patient.
AB  - A 73-year-old man presented with acute chest pain and shortness of breath
      suggestive of unstable angina. A detailed investigation revealed essential
      thrombocythemia and coronary artery pathology. With a baseline platelet count of
      2,650*10(3)/MUL, coronary artery bypass grafting became nearly impossible. Three
      therapeutic plateletpheresis procedures successfully lowered the platelet count
      to 367*10(3)/MUL. Thereafter, surgery was performed with no complications.
      Although a drop and rise in platelet counts were observed postoperatively, the
      patient could be discharged in stable condition after 14 days. Thus, therapeutic
      plateletpheresis reduces platelet count rapidly in essential thrombocythemia and
      relieves patients of acute symptoms.

PMID- 21718823
TI  - Spontaneous pneumothorax after traumatic pneumonectomy: a role for talc
      pleurodesis in secondary prevention?
AB  - We report a case of spontaneous contralateral pneumothorax 2 months after a
      pneumonectomy, with the initial placement of an intercostal chest drain on the
      side of the pneumothorax. Due to the high risk of a subsequent life-threatening
      pneumothorax, pleurodesis became an important consideration. Surgical pleurodesis
      can be complicated by the risks of single lung ventilation; therefore, talc
      pleurodesis was performed by using the intercostal drain once the lung had fully
      expanded. The patient remains free of recurrence 14 months after the
      pneumonectomy. Our case suggests that talc may be an effective alternative method
      of secondary prevention of a pneumothorax after a pneumonectomy.

PMID- 21718824
TI  - The fork in the road.

PMID- 21718825
TI  - The right internal thoracic artery: the forgotten conduit--5,766 patients and 991
      angiograms.
AB  - BACKGROUND: The right internal thoracic artery (RITA) is biologically identical
      to the left ITA, yet is rarely used in coronary artery bypass graft surgery
      (CABG). We examined the results and long-term patency of RITA grafts. METHODS:
      Between 1986 and 2008, 991 consecutive RITA graft angiograms for postoperative
      cardiac symptoms were evaluated by two independent observers. Grafts were
      considered nonpatent if they had a greater than 80% stenosis, string sign, or
      total occlusion. Patency was examined over time by coronary territory, whether in
      situ or free RITA, and compared with other conduits. Clinical results were
      collected prospectively and by the National Death Index. RESULTS: A total of
      5,766 patients had a RITA graft as part of a bilateral ITA CABG procedure.
      Operative mortality was 1.1%; deep sternal infection 1.5%. Of 7,780 coronary
      conduits studied, 991 RITA conduits were examined; a mean of 100+/-60 months
      postoperatively (1 to 288 months). Overall ten-year RITA patency was 90%. The
      RITA graft patency to the left anterior descending artery (LAD; n=149) was 95% at
      10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal
      (Cx; n=436) was 91%, right coronary artery (n=199) was 84% (p<0.001), and
      posterior descending artery (n=207) was 86%. Ten-year RITA and LITA patencies to
      the LAD were identical (95% vs 96%) and to the Cx (91% vs 89%), respectively. In
      situ RITA (n=450) and free RITA (n=541) had similar ten-year patencies (89% vs
      91%; p=0.44). The RITA patency was always better than the radial artery (p<0.01)
      and saphenous vein grafts (p<0.001). Atheromatous changes were not seen in the
      RITA angiograms. Ten-year survival of patients with RITA and LITA for triple
      vessel coronary disease was 89%. CONCLUSIONS: Late patencies of RITA are
      excellent, equivalent to the LITA for identical territories, always better than
      radial arteries and saphenous vein grafts, and remain free of atheroma. Use of
      RITA in addition to LITA is associated with excellent survival in triple-vessel
      coronary disease. More extensive use of the RITA in CABG is recommended.

PMID- 21718826
TI  - Transapical aortic valve implantation off-pump in patients with impaired left
      ventricular function.
AB  - BACKGROUND: Patients with impaired left ventricular ejection fraction (LVEF) and
      severe aortic stenosis have a higher perioperative risk for aortic valve
      replacement. Transapical aortic valve implantation (TA-AVI) allows for off-pump
      valve implantation, which might be beneficial in the subgroup of patients with
      impaired LVEF. METHODS: All patients with LVEF<=40% who underwent TA-AVI for
      severe aortic stenosis and who fulfilled at least 1-year follow-up formed the
      study group. Results were compared to TA-AVI patients with preserved LVEF treated
      during the same time period. RESULTS: Thirty-nine patients with LVEF<=40% were
      identified, mean LVEF was 32.5+/-7.1%. Logistic EuroSCORE and STS-score were
      43.6%+/-18.5% and 15.3%+/-9.3%, respectively. Concomitant coronary artery disease
      was present in 59% with 23.1% having had previous bypass surgery and 17.9% having
      had a history of prior myocardial infarction. Two patients required
      cardiopulmonary-bypass support due to intraoperative complications, and another 2
      patients required cardiopulmonary-bypass for reperfusion. Median procedure time
      was 75 minutes (interquartile range, 65-90 minutes). LVEF at discharge increased
      significantly to a mean of 41.5%+/-10%, and at 1-year follow-up to 53.9%+/-13%
      (both p<0.0001). The proportion of patients in New York Heart Association class
      III-IV decreased from 92.3% to 15.0% at 1-year follow-up (p<0.001). There was
      neither a statistically significant difference in in-hospital mortality nor in
      long-term survival up to 4 years, in comparison to patients with preserved LVEF.
      CONCLUSIONS: Transapical aortic valve implantation is a promising approach,
      allowing for off-pump treatment of elderly, high-risk patients with impaired LVEF
      requiring aortic valve replacement. Short-term and long-term outcomes are
      respectable, and an improvement in postoperative LVEF and New York Heart
      Association class can be anticipated.

PMID- 21718827
TI  - Invited commentary.

PMID- 21718828
TI  - Successful linking of the Society of Thoracic Surgeons database to social
      security data to examine survival after cardiac operations.
AB  - BACKGROUND: Long-term evaluation of cardiothoracic surgical outcomes is a major
      goal of The Society of Thoracic Surgeons (STS). Linking the STS Database to the
      Social Security Death Master File (SSDMF) allows for the verification of "life
      status." This study demonstrates the feasibility of linking the STS Database to
      the SSDMF and examines longitudinal survival after cardiac operations. METHODS:
      For all operations in the STS Adult Cardiac Surgery Database performed in 2008 in
      patients with an available Social Security Number, the SSDMF was searched for a
      matching Social Security Number. Survival probabilities at 30 days and 1 year
      were estimated for nine common operations. RESULTS: A Social Security Number was
      available for 101,188 patients undergoing isolated coronary artery bypass
      grafting, 12,336 patients undergoing isolated aortic valve replacement, and 6,085
      patients undergoing isolated mitral valve operations. One-year survival for
      isolated coronary artery bypass grafting was 88.9% (6,529 of 7,344) with all vein
      grafts, 95.2% (84,696 of 88,966) with a single mammary artery graft, 97.4% (4,422
      of 4,540) with bilateral mammary artery grafts, and 95.6% (7,543 of 7,890) with
      all arterial grafts. One-year survival was 92.4% (11,398 of 12,336) for isolated
      aortic valve replacement (95.6% [2,109 of 2,206] with mechanical prosthesis and
      91.7% [9,289 of 10,130] with biologic prosthesis), 86.5% (2,312 of 2,674) for
      isolated mitral valve replacement (91.7% [923 of 1,006] with mechanical
      prosthesis and 83.3% [1,389 of 1,668] with biologic prosthesis), and 96.0% (3,275
      of 3,411) for isolated mitral valve repair. CONCLUSIONS: Successful linkage to
      the SSDMF has substantially increased the power of the STS Database. These
      longitudinal survival data from this large multi-institutional study provide
      reassurance about the durability and long-term benefits of cardiac operations and
      constitute a contemporary benchmark for survival after cardiac operations.

PMID- 21718829
TI  - Changing pattern of reoperative coronary artery bypass grafting: a 20-year study.
AB  - BACKGROUND: Fewer patients are undergoing reoperative coronary artery bypass
      grafting (CABG). We investigated the prevalence of redo vs primary CABG and
      previous percutaneous coronary intervention (PCI), changing trends in
      preoperative risk profiles, and independent predictors of operative death.
      METHODS: Data on demographic characteristics, preoperative risk factors, and
      hospital outcomes were collected prospectively for patients undergoing isolated
      reoperative CABG from January 1, 1990, to December 31, 2009. To examine the
      effect of time on the prevalence of redo CABG cases and previous PCI, we divided
      patients into four groups: 1990 through 1994, 470; 1995 through 1999, 415; 2000
      through 2004, 240; and 2005 through 2009, 79. To examine risk profiles and
      outcomes, we created two groups: 1990 through 1999, 885; 2000 through 2009, 319.
      RESULTS: Redo CABG decreased from 7.2% (1990 through 1994) to 2.2% (2005 through
      2009). PCI before redo CABG significantly increased from 14.5% (1990 through
      1994) to 26.6% (2005 through 2009). Patients with diabetes, dyslipidemia,
      hypertension, peripheral vascular disease, and left main disease increased. In
      hospital mortality did not change significantly, but postoperative low cardiac
      output syndrome dropped. Age (odds ratio [OR], 1.04), peripheral vascular disease
      (OR, 2), congestive heart failure (OR, 5.8), and preoperative shock (OR. 9.7)
      independently predicted higher operative mortality. CONCLUSIONS: Reoperative CABG
      has significantly decreased. The increased prevalence of PCI before redo CABG is
      one of the reasons. Despite an increasing risk profile, hospital outcomes have
      remained largely the same. Preoperative shock and congestive heart failure are
      the most important predictors of operative mortality.

PMID- 21718830
TI  - Skeletonized internal thoracic artery harvest improves prognosis in high-risk
      population after coronary artery bypass surgery for good quality grafts.
AB  - BACKGROUND: Skeletonization of the internal thoracic artery is supposed to
      achieve extra length with added advantages of decreased sternal complications.
      There is no agreement whether skeletonization affects grafts, main adverse
      cardiac events, mortality, or pulmonary function when compared with the
      conventional pedicled method. The aim of our study was to determine the
      effectiveness and safety of different harvesting techniques. METHODS: A
      systematic search of the literature was undertaken of all control trials
      comparing the skeletonized and pedicled internal thoracic artery in MEDLINE,
      EMBASE, and the Cochrane Library. RESULTS: Twenty-three trials between 1966 and
      2010 were identified as eligible. Combined weighted mean difference demonstrated
      a significant increase in the length (1.99 cm, 95% confidence interval [CI] 0.87
      3.11.), caliber (0.13 mm, 95% CI 0.07-0.20) and flow capacity (23.24 ml/min, 95%
      CI 7.52-38.96) for skeletonization, with comparable angiographic results at
      midterm follow-up as the pedicled harvesting. Perhaps resulting from better
      preservation of sternal perfusion, patients with skeletonized internal thoracic
      artery experienced fewer relative risks in sternal wound infection (p=0.017) and
      less scores in chest wall pain (p=0.033). Moreover, the meticulous skeletonized
      dissection can minimize the trauma to reduce blood loss and intubation time, in
      spite of time consuming. Above all, in the high-risk population, skeletonization
      was associated with improved prognosis, with fewer mainly adverse cardiac events
      (relative risk 0.38; 95% CI 0.14 to 0.99) and mortality (relative risk 0.70; 95%
      CI 0.50 to 0.98). CONCLUSIONS: Skeletonized harvesting for the internal thoracic
      artery provides superiority to the quality of grafts with additional advantages
      of lesser trauma, producing fewer postoperative complications. Above all,
      skeletonized grafting in the high-risk population has a potential benefit in
      mortality and mainly adverse cardiac events.

PMID- 21718831
TI  - Invited commentary.

PMID- 21718832
TI  - Invited commentary.

PMID- 21718833
TI  - Undersized tricuspid annuloplasty rings optimally treat functional tricuspid
      regurgitation.
AB  - BACKGROUND: In contrast to mitral valve repair, residual and recurrent
      regurgitation after tricuspid valve (TV) repair for functional tricuspid
      regurgitation (TR) is common. We have systematically used undersized, rigid 3
      dimensional annuloplasty rings to treat functional TR. METHODS: From March 2006
      to October 2009, 101 consecutive patients with moderate or greater functional TR
      underwent TV repair with an undersized rigid 3-dimensional annuloplasty ring. All
      patients had a predischarge echocardiography evaluation in a core
      echocardiography laboratory. Follow-up echocardiography was available for 96% of
      surviving patients. Mean follow-up was 17+/-9 months. RESULTS: Twenty-nine
      percent of patients had undergone previous cardiac operations, 74% were in New
      York Heart Association functional class III or IV, and 48% had atrial
      fibrillation. Mitral valve operations were performed in 93 patients, aortic valve
      operations in 17, coronary artery bypass grafting in 21, and CryoMaze procedures
      in 40. Size 26 or 28 rigid tricuspid annuloplasty rings were used in 88% of
      patients, and no ring larger than a 28 has been used since November 2008. The
      operative mortality rate was 6% (n=6). Freedom from significant TR (TR>moderate)
      at hospital discharge, as assessed by the clinical core laboratory, was 97%. Only
      3% of patients had TR greater than moderate during follow-up. No patient required
      TV reoperation. New postoperative permanent pacemakers were inserted in 3
      patients. CONCLUSIONS: Tricuspid valve repair with an undersized (size 26 or 28)
      rigid 3-dimensional annuloplasty ring is the method of choice for reliable and
      durable treatment of functional TR.

PMID- 21718834
TI  - Results with a selective revascularization strategy for left subclavian artery
      coverage during thoracic endovascular aortic repair.
AB  - BACKGROUND: The need for routine left subclavian artery (LSCA) revascularization
      when this vessel is covered during thoracic endovascular aortic repair remains
      controversial. We report our results with a selective LSCA revascularization
      strategy during thoracic endovascular aortic repair. METHODS: Between May 2002
      and March 2010, 287 thoracic endovascular aortic repair procedures were performed
      at our institution. LSCA coverage occurred in 145 (51%), which form the basis of
      this report. RESULTS: Left subclavian artery revascularization was performed in
      32 patients (22%) through a left common carotid-LSCA bypass. Indications for
      selective LSCA revascularization included spinal cord protection in 10, patent
      pedicled left internal mammary artery graft in 9, left arm ischemia after LSCA
      coverage in 5, origin of the left vertebral artery from the arch in 4, dialysis
      access in the left arm in 2, and vertebrobasilar insufficiency in 2. There were
      no instances of dominant left vertebral artery. The revascularized and non
      revascularized groups had similar rates of death (6.3% vs 1.8%; p=0.21), stroke
      (3.1% vs 3.5%; p>0.99), permanent paraplegia or paraparesis (3.1% vs 0%; p=0.22),
      and type II endoleak (4.3% vs 6.5%; p>0.99). There were no instances of ischemic
      stroke related to left posterior circulation hypoperfusion. Four complications of
      carotid-subclavian bypass occurred in 3 patients (9.4%). CONCLUSIONS: Selective
      LSCA revascularization is safe and does not appear to increase the risk of
      neurologic events. Further, subclavian revascularization is not without
      complications, which should be considered with regards to a nonselective
      revascularization strategy.

PMID- 21718835
TI  - Substrate modifications precede the development of atrial fibrillation after
      cardiac surgery: a proteomic study.
AB  - BACKGROUND: Atrial fibrillation (AF) is an important cause of morbidity and
      mortality after cardiac surgery. The pathogenesis of AF appears to be
      multifactorial but little is known about the cause-effect relationship of
      substrate modifications with the onset of the arrhythmia. With the use of modern
      proteomics, this study aims to identify preexisting changes in the left atrium of
      patients susceptible to postoperative AF. METHODS: We analyzed 20 matched
      patients undergoing elective, first-time coronary artery bypass grafting with no
      history of AF. They were divided into 2 equal groups according to the development
      of postoperative AF. Proteomic analysis was performed in left atrial tissue
      obtained during surgery using two-dimensional difference in gel electrophoresis
      techniques. Mass spectrometry identified proteins that were differentially
      expressed in patients who developed AF against those who remained in sinus
      rhythm. RESULTS: Proteomic analysis of left atrial tissue identified 19
      differentially expressed protein spots between patients who developed
      postoperative AF and their sinus rhythm counterparts. In patients who developed
      AF, proteins associated with oxidative stress and apoptosis (peroxiredoxin 1,
      apoptosis-inducing factor, and 96S protease regulatory subunit 8) as well as
      acute phase response components (apolipoprotein A-I, fibrinogen) were found to be
      increased. Conversely, the expression of proteins responsible for glycolysis
      (enolase) and pyruvate metabolism (pyruvate dehydrogenase) was reduced.
      CONCLUSIONS: We describe protein changes that precede the development of
      postoperative AF and which might be suggestive of increased oxidative stress and
      glycolytic inhibition in the left atrium of patients predilected to AF.

PMID- 21718836
TI  - Leukocyte filtration ameliorates the inflammatory response in patients with mild
      to moderate lung dysfunction.
AB  - BACKGROUND: Chronic obstructive pulmonary disease is a risk factor for
      postoperative lung injury. Contradictory results have been published about
      leukocyte filtration (LF) because of the heterogeneity of patients and
      interventions, type of LF, and comorbidities. METHODS: Sixty patients with mild
      moderate chronic obstructive pulmonary disease (forced expiratory volume in 1
      second 40% to 80%) undergoing aortic valve surgery were randomly assigned to
      receive systemic arterial and cardioplegic LF during cardiopulmonary bypass
      (group L, 30 patients) or standard cardiopulmonary bypass (group S).
      Perioperative interleukin-6, interleukin-8, and tumor necrosis factor-alpha were
      sampled at different time points. The PaO2/inspired oxygen fraction (FiO2) and
      alveoloarterial oxygen gradient (AaDO2) were measured preoperatively, at
      intensive care unit arrival, and at 24, 48, and 72 hours postoperatively; lung
      compliance was measured after intubation, at intensive care unit arrival, and at
      4 and 8 hours postoperatively; and radiographic lung injury score was determined
      preoperatively and at 24, 48 and 72 hours. Length of intubation, intensive care
      unit stay, hospital stay, need for noninvasive positive-pressure ventilation,
      acute lung injury, and pneumonia were recorded. Repeated-measures analysis of
      variance assessed group, time, and group by-time interactions. RESULTS:
      Preoperative and intraoperative data were comparable. Proinflammatory cytokine
      leakage was reduced by LF. Group L showed shorter intubation time (median 9.5
      hours versus group S, 15.0 hours; p=0.0001), and intensive care unit length of
      stay (median 19.0 hours versus group S, 24.5; p=0.0001), lower need for
      noninvasive positive-pressure ventilation (5 of 30, 16.7%, versus 12 of 30, 40%;
      p=0.042). The AaDO2, PaO2/FiO2, lung compliance, and radiographic lung injury
      score worsened early postoperatively, followed by progressive improvements (time
      p<=0.001 for all). Such decline of AaDO2, PaO2/FiO2, lung compliance, and
      radiographic lung injury score was significantly attenuated by LF (group by-time
      p=0.0001 for AaDO2, PaO2/FiO2, and lung compliance; p=0.004 for radiographic lung
      injury score). CONCLUSIONS: Arterial plus cardioplegic LF significantly reduced
      proinflammatory cytokine release after cardiopulmonary bypass, thus ameliorating
      postoperative indexes of lung function and overall respiratory outcome.

PMID- 21718837
TI  - Risk factors and early outcomes of multiple reoperations in adults with
      congenital heart disease.
AB  - BACKGROUND: Advances in treatment of congenital heart disease (CHD) have resulted
      in most patients surviving to adulthood. Despite surgical "correction," the need
      for reoperation(s) persists, and there are few outcome data. This study examined
      early postoperative results to determine risk factors for cardiac injury and
      early death in adults with CHD undergoing repeat median sternotomy. METHODS: Data
      from the most recent median sternotomy of 984 adults (49% male) with CHD were
      analyzed. Mean age at operation was 36.4 years. Diagnoses were conotruncal
      anomaly, 361 (37%); Ebstein/Tricuspid valve, 174 (18%); pulmonary stenosis/right
      ventricular outflow tract obstruction, 92 (9%); single ventricle, 71 (7%);
      atrioventricular septal defect, 64 (7%); subaortic stenosis, 62 (6%); aortic arch
      abnormalities, 23 (2%); anomalous pulmonary vein, 21 (2%); Marfan syndrome, 14
      (1%); and other, 102 (10%). RESULTS: Overall early mortality was 3.6%: including
      2%, 6%, 7%, and 0% at sternotomy 2 (n=597), 3 (n=284), 4 (n=72), and 5+ (n=31),
      respectively. Cardiac injury occurred in 6%. Independent predictors of cardiac
      injury were single-ventricle diagnosis and increased number of prior
      sternotomies. Increased time from previous sternotomy decreased the incidence of
      cardiac injury. Independent risk factors for early death were urgent operation,
      single-ventricle diagnosis, and longer bypass time. Increased preoperative
      ejection fraction decreased early mortality. CONCLUSIONS: Subsequent sternotomy
      showed increased early mortality, yet neither sternotomy number nor cardiac
      injury was an independent predictor of early death. Two variables were
      protective: early mortality was reduced with increased ejection fraction and
      cardiac injury was less likely with increased interval from the previous
      sternotomy.

PMID- 21718838
TI  - Performance and morphology of decellularized pulmonary valves implanted in
      juvenile sheep.
AB  - BACKGROUND: Because of cryopreserved heart valve-mediated immune responses,
      decellularized allograft valves are an attractive option in children and young
      adults. The objective of this study was to investigate the performance and
      morphologic features of decellularized pulmonary valves implanted in the right
      ventricular outflow tract of juvenile sheep. METHODS: Right ventricular outflow
      tract reconstructions in juvenile sheep (160+/-9 days) using cryopreserved
      pulmonary allografts (n=6), porcine aortic root bioprostheses (n=4), or
      detergent/enzyme-decellularized pulmonary allografts (n=8) were performed. Valve
      performance (echocardiography) and morphologic features (gross, radiographic, and
      histologic examination) were evaluated 20 weeks after implantation. RESULTS:
      Decellularization reduced DNA in valve cusps by 99.3%. Bioprosthetic valves had
      the largest peak and mean gradients versus decellularized valves (p=0.03;
      p<0.001) and cryopreserved valves (p=0.01; p=0.001), which were similar (p=0.45;
      p=0.40). Regurgitation was minimal and similar for all groups (p=0.16). No cusp
      calcification was observed in any valve type. Arterial wall calcification was
      present in cryopreserved and bioprosthetic grafts but not in decellularized
      valves. No autologous recellularization or inflammation occurred in
      bioprostheses, whereas cellularity progressively decreased in cryopreserved
      grafts. Autologous recellularization was present in decellularized arterial walls
      and variably extending into the cusps. CONCLUSIONS: Cryopreserved and
      decellularized graft hemodynamic performance was comparable. Autologous
      recellularization of the decellularized pulmonary arterial wall was consistently
      observed, with variable cusp recellularization. As demonstrated in this study,
      decellularized allograft valves have the potential for autologous
      recellularization.

PMID- 21718839
TI  - Staged approach prevents spinal cord injury in hybrid surgical-endovascular
      thoracoabdominal aortic aneurysm repair: an experimental model.
AB  - BACKGROUND: In a porcine model, we investigated the impact of sudden stent graft
      occlusion of thoracic intercostal arteries after open lumbar segmental artery
      (SA) ligation. METHODS: After randomization into two groups, 20 juvenile
      Yorkshire pigs (27.1+/-0.6 kg) underwent open lumbar SA sacrifice (T13-L5)
      followed by endovascular coverage of all thoracic SAs (T4-T12) at 32 degrees C,
      either in a single operation (group 1) or in two stages separated by seven days
      (group 2). Collateral network pressure (CNP) was monitored by catheterization of
      the SA L1, and postoperative hind limb function was assessed using a modified
      Tarlov score. RESULTS: The CNP in group 1 decreased to 34% of baseline, whereas
      CNP after lumbar SA ligation in group 2 fell to 55% of baseline (74+/-2.4 to 25+/
      3.6 mm Hg vs 74+/-4.5 to 41+/-5.5 mm Hg; p<0.0001). Subsequent thoracic stenting
      (group 2) led to another significant but milder drop (p=0.002 versus stage 1)
      from the restored CNP (71+/-4.2 to 54+/-4.9 mm Hg). Five of ten pigs in group 1
      suffered paraplegia, in contrast to none in group 2 (median Tarlov score 6, vs 9;
      p=0.0031). Histopathologic analysis showed more severe ischemic damage to the
      lower thoracic (p=0.05) and lumbar spinal cord (p=0.002) in group 1. CONCLUSIONS:
      These results underline the potential of the staged approach in hybrid
      procedures. Furthermore they highlight the need for established adjuncts for
      preventing paraplegia in hybrid and pure stent-graft protocols in which sudden
      occlusion of multiple SAs occurs.

PMID- 21718840
TI  - Aortic valve cyclic stretch causes increased remodeling activity and enhanced
      serotonin receptor responsiveness.
AB  - BACKGROUND: Increased serotonin (5-hydroxytryptamine [5HT]) receptor (5HTR)
      signaling has been associated with cardiac valvulopathy. Prior cell culture
      studies of 5HTR signaling in heart valve interstitial cells have provided
      mechanistic insights concerning only static conditions. We investigated the
      hypothesis that aortic valve biomechanics participate in the regulation of both
      5HTR expression and interrelated extracellular matrix remodeling events. METHODS:
      The effects of cyclic stretch on aortic valve 5HTR, expression, signaling, and
      extracellular matrix remodeling were investigated using a tensile stretch
      bioreactor in studies which also compared the effects of adding 5HT and (or) the
      5HT-transporter inhibitor, fluoxetine. RESULTS: Cyclic stretch alone increased
      both proliferation and collagen in porcine aortic valve cusp samples. However,
      with cyclic stretch, unlike static conditions, 5HT plus fluoxetine caused the
      greatest increase in proliferation (p<0.0001), and also caused significant
      increases in collagen (p<0.0001) and glycosaminoglycans (p<0.0001). The DNA
      microarray data demonstrated upregulation of 5HTR2A and 5HTR2B (>4.5-fold) for
      cyclic stretch versus static (p<0.001), while expression of the 5HT transporter
      was not changed significantly. Extracellular matrix genes (eg, collagen types I,
      II, III, and proteoglycans) were also upregulated by cyclic stretch. CONCLUSIONS:
      Porcine aortic valve cusp samples subjected to cyclic stretch upregulate 5HTR2A
      and 2B, and also initiate remodeling activity characterized by increased
      proliferation and collagen production. Importantly, enhanced 5HTR responsiveness
      due to increased 5HTR2A and 2B expression results in a significantly greater
      response in remodeling endpoints (proliferation, collagen, and GAG production) to
      5HT in the presence of 5HT transporter blockade.

PMID- 21718841
TI  - Invited commentary.

PMID- 21718842
TI  - Crimping may affect the durability of transcatheter valves: an experimental
      analysis.
AB  - BACKGROUND: Transcatheter aortic valve implantation has gained widespread
      acceptance to treat elderly high-risk patients with aortic stenosis. We used a
      subcutaneous rat model to evaluate whether crimping may affect valve long-term
      durability. METHODS: Standard Sapien transcatheter valves (Edwards Lifesciences,
      Irvine, CA) were crimped for different durations (1 hour, 1 day, 1 month) and
      uncrimped, and leaflet pieces as well as control tissue (Perimount Magna,
      Edwards) were then implanted subcutaneously in 15 male weanling Sprague-Dawley
      rats for 12 weeks. Grade of calcification was measured by freeze-dried mass and
      van Kossa staining. Histologic and electron microscopic examination were
      performed to investigate potential leaflet-fragmentation caused by crimping.
      RESULTS: There were no differences in calcification among the groups. The calcium
      carbonate concentrations in all samples ranged from 0.1 to 100 mg/g dry weight.
      Leaflet morphology, however, differed from no fragmentation (control group) to
      highly fragmented tissue (1-month crimped). These differences reached statistical
      significance between crimped and non-crimped leaflets (p<0.003). CONCLUSIONS:
      Transcatheter valve crimping does not necessarily affect leaflet calcification.
      However, the structural changes of the leaflets that were caused by crimping may
      have clinical significance. Duration of crimping should be as short as possible,
      and very tight crimping to small diameters should be avoided.

PMID- 21718843
TI  - Invited commentary.

PMID- 21718844
TI  - Invited commentary.

PMID- 21718845
TI  - Totally thoracoscopic surgical closure of atrial septal defect in small children.
AB  - BACKGROUND: Totally thoracoscopic cardiac surgery is an alternative to
      traditional cardiac surgery in adults, and in few cases, in small children. This
      study assesses totally thoracoscopic cardiac surgery and its advantages for
      application to small children with low body weight. METHODS: From March 2009 to
      October 2010, 28 patients, with a mean age of 5.8+/-2.1 years and mean weight of
      15.0+/-4.65 kg (range, 13.5 to 22 kg), underwent totally thoracoscopic atrial
      septal defect closure. Three incisions 1.0 cm to 2.5 cm in length were made on
      the chest wall. Direct sutures were made in 20 patients, whereas Dacron patches
      were used in 8 patients. Mean follow-up was 6 months (range, 0 to 24 months).
      RESULTS: Cardiopulmonary bypass time was 56 to 126 minutes, and the aortic cross
      clamp time was 36 to 65 minutes. A total of 28 cases were classified as New York
      Heart Association functional class I. No patient required further operation.
      CONCLUSIONS: Totally thoracoscopic surgical atrial septal defect closure in small
      children is feasible, minimally invasive, safe, and has good cosmesis.

PMID- 21718846
TI  - Current concepts in the management of esophageal perforations: a twenty-seven
      year Canadian experience.
AB  - BACKGROUND: Perforation of the esophagus remains a challenging clinical problem.
      METHODS: A retrospective review was performed of patients diagnosed with an
      esophageal perforation admitted to the London Health Sciences Centre from 1981 to
      2007. Univariate and multivariate logistic regression was used to determine which
      factors had a statistically significant effect on mortality. RESULTS: There were
      119 patients; 15 with cervical, 95 with thoracic, and 9 with abdominal
      perforations. Fifty-one percent of all the perforations were iatrogenic and 33%
      were spontaneous. Multivariate logistic regression analysis revealed that
      patients with preoperative respiratory failure requiring mechanical ventilation
      had a mortality odds ratio of 32.4 (95% confidence interval [CI] 3.1 to 272.0),
      followed by malignant perforations with 20.2 (95% CI 5.4 to 115.6), a Charlson
      comorbidity index of 7.1 or greater with 19.6 (95% CI 4.8 to 84.9), the presence
      of a pulmonary comorbidity with 13.9 (95% CI 2.9 to 97.4), and sepsis with 3.1
      (95% CI 1.0 to 10.1). A wait time of greater than 24 hours was not associated
      with an increased risk of mortality (p=0.52). CONCLUSIONS: Malignant
      perforations, sepsis, mechanical ventilation at presentation, a higher overall
      burden of comorbidity, and a pulmonary comorbidity have a significant impact on
      the overall survival. Time to treatment is not as important. Restoration of
      intestinal continuity, either by primary repair or by excision and reanastomosis
      can be attempted even in patients with a greater time from perforation to
      treatment with respectable morbidity and mortality rates.

PMID- 21718847
TI  - Modification of nodal categories in the seventh american joint committee on
      cancer staging system for esophageal squamous cell carcinoma in Chinese patients.
AB  - BACKGROUND: More data are essential to test the efficacy of the American Joint
      Committee on Cancer (AJCC) system for staging esophageal squamous cell carcinoma.
      We tested the classifiers used in the AJCC staging system and propose a
      modification to this system to better represent the survival characteristics of
      esophageal squamous cell carcinoma in the Chinese population. METHODS: We used
      data from two centers, which established the training (n=1,006) and validation
      (n=783) cohorts. All the patients underwent curative surgical treatment. Survival
      was compared using AJCC classifiers to test the efficacy of this staging system.
      Martingale residuals from a Cox proportional hazards regression model were used
      to modify the nodal categories. The results obtained from the training cohort
      were validated with the validation cohort at each step. RESULTS: The evaluation
      of the patients' overall survival allowed only poor discrimination between AJCC
      IIIb and IIIc cancers in both cohorts. Also, in both cohorts, N2 and N3
      classification cancers could not be well discriminated in terms of survival when
      AJCC nodal categories were used. Nevertheless, the survival rate could easily be
      distinguished when using the four modified categories: 0, 1, 2 to 3, and 4 or
      more positive nodes. The survival difference between IIIb and IIIc obtained using
      the modified nodal categories could easily be discriminated in both cohorts.
      CONCLUSIONS: Esophageal squamous cell carcinoma nodal staging for the Chinese
      population was more accurately classified using the following four categories: no
      positive node, 1 positive node, 2 to 3 positive nodes, and 4 or more positive
      nodes. Further studies are required to confirm these results.

PMID- 21718848
TI  - Invited commentary.

PMID- 21718849
TI  - Efficacy of mediastinal lymph node dissection during lobectomy for lung cancer by
      thoracoscopy and thoracotomy.
AB  - BACKGROUND: Mediastinal lymph node dissection (MLND) is an integral component of
      complete resection for non-small cell lung cancer (NSCLC). This study analyzed
      the National Comprehensive Cancer Network's (NCCN) NSCLC Database to compare the
      efficacy of MLND during lobectomy by video-assisted thoracoscopy surgery (VATS)
      and thoracotomy (open). METHODS: The NCCN NSCLC Database was queried to identify
      patients who underwent lobectomy to analyze the adequacy of MLND by the number of
      LN stations. The percentage of patients with at least three N2 stations, the
      number of N2 LN stations, and the total number of LN stations (N1+N2) resected
      was compared by approach. RESULTS: Of 4215 patients with NSCLC (January 2007 to
      September 2010), 388 patients underwent lobectomy (199 VATS and 189 open) and met
      entry criteria. The groups were similar in age, sex, comorbidities, performance
      status, and histology. MLN assessment was similar in both groups as measured by
      number of N2 stations (median, 3 stations; p=0.12). At least three MLN stations
      were assessed in 130 patients (66%) in the VATS group vs 107 patients (58%) in
      the open group (p=0.12). The total number of N1+N2 stations resected for each
      group was also similar (median, 4 in both groups (p=0.06). CONCLUSIONS: The NCCN
      database indicates at least three MLN stations were assessed in most patients who
      underwent lobectomy by either approach. As evaluated by the number of LN
      stations, there was no difference in the efficacy of MLN dissection by approach.

PMID- 21718850
TI  - Impact of laterality on early and late survival after pneumonectomy.
AB  - BACKGROUND: This study evaluated the effect of laterality on survival in patients
      who underwent pneumonectomy for lung cancer. METHODS: We reviewed the
      Surveillance, Epidemiology, and End Results (SEER) database for patients who
      underwent pneumonectomy for lung cancer from 1988 through 2006. Predictors of
      survival were determined by univariate and multivariable analysis. RESULTS: A
      total of 9746 patients had pneumonectomies. Left pneumonectomies (56%) were more
      common than right; 67% of patients were men with mean age of 63 years (range, 12
      to 92 years). Tumor pathology was squamous cell in 49% and adenocarcinoma in 34%.
      Stage distribution was stage I, 28%; stage II, 28%; stage IIIA, 19%; stage IIIB,
      18%; and stage IV, 6%. Overall survival was 67% and 40%, respectively, at 1 and 3
      years; with 63% and 39% for right vs 70% and 41% for left (p<0.001). Mortality at
      1 and 3 months was 8% and 16% for right pneumonectomies and 4% and 9% for left
      (p<0.001). Multivariate predictors of worse survival were right pneumonectomy,
      age, stage, male sex, tumor size, grade, prior malignancy, not married, number of
      positive lymph nodes, and fewer lymph nodes evaluated (all p<0.05). The adjusted
      hazard ratio for right pneumonectomy was 1.12 (95% confidence interval, 1.07 to
      1.18; p<0.00001). For 3-month survival, right pneumonectomy had an adjusted odds
      ratio of 2.01 (95% confidence interval, 1.77 to 2.29; p<0.001). Neoadjuvant
      radiotherapy did not affect 3-month survival (adjusted odds ratio, 0.88; 95%
      confidence interval, 0.1 to 7.03, p=0.9). CONCLUSIONS: A right pneumonectomy is
      associated with approximately twice the perioperative mortality as a left
      pneumonectomy. However, neoadjuvant radiotherapy does not appear to add
      incremental risk, and long-term survival is not affected by laterality.

PMID- 21718851
TI  - Invited commentary.

PMID- 21718852
TI  - Invited commentary.

PMID- 21718853
TI  - Extracorporeal membrane oxygenation support for resection of locally advanced
      thoracic tumors.
AB  - BACKGROUND: The international experience with resection of advanced thoracic
      malignancies performed with extracorporeal membrane oxygenation (ECMO) support is
      limited. We examined our results to assess the risks and benefits of this
      approach. METHODS: We retrospectively analyzed all patients with thoracic
      malignancies who underwent tumor resection with ECMO support in our department
      between 2001 and 2010. RESULTS: Nine patients (aged 21 to 71 years; mean, 54.8+/
      7.5 years) underwent complex tracheobronchial resections (n=6) or resections of
      greater thoracic vessels (n=3) under venoarterial (VA) ECMO support. In 7
      patients the underlying pathologic condition was non-small cell lung cancer, in 1
      patient it was carcinoid tumor, and in 1 patient it was synovial sarcoma. The
      indication for extracorporeal support was complex tracheobronchial reconstruction
      (n=5), resection of the descending aorta (n=2), and resection of the inferior
      vena cava (n=1). ECMO cannulation was central (n=4), peripheral (n=4), or
      combined (n=1). Mean time on bypass was 110+/-19 minutes (range 40 to 135
      minutes). A complete resection (R0) was achieved in 8 patients (89%). One patient
      died perioperatively as a result of hepatic necrosis. Eight patients were
      discharged from the hospital after 7 to 42 days (median, 10 days). Median time in
      the intensive care unit was 1 day (range, 0 to 36 days). The only complication
      related to the use of ECMO was a lymphatic fistula in the groin. Mean follow-up
      time was 38+/-42 months (range, 9 to 111 months). The actuarial 3-month survival
      was 88.9%, and the 1-year, 3-year, and 5-year survival was 76.7%. CONCLUSIONS:
      Based on this experience, we consider VA ECMO support to be a safe alternative to
      cardiopulmonary bypass (CPB) for advanced general thoracic operations.

PMID- 21718854
TI  - Invited commentary.

PMID- 21718855
TI  - Standardized combined outcome index as an instrument for monitoring performance
      after pulmonary resection.
AB  - BACKGROUND: Modern healthcare systems demand more transparent and accurate
      monitoring of clinical performance with the purpose to improve standards of care
      in a cost-effective way. Outcomes, such as mortality, are still the most widely
      used quality indicators in our specialty. However, previous studies have shown
      that mortality alone does not reflect performance accurately in our specialty.
      Ideally, multiple risk-adjusted outcomes should be used for a more comprehensive
      assessment. The objective of this analysis was to develop and use an index
      combining multiple risk-adjusted outcomes to track down the performance of our
      thoracic surgery unit over time. METHODS: In all, 511 major lung resections (465
      lobectomies, 46 pneumonectomies) performed from January 2005 through September
      2010 were analyzed. Four risk-adjusted outcomes were considered: 30 days or in
      hospital mortality, cardiopulmonary morbidity, unplanned/emergency intensive care
      unit admission, and prolonged length of stay (more than 14 days, prolonged
      hospital stay). Risk adjustment was performed using published regression models.
      Each indicator was converted into its opposite (ie, mortality rate to survival
      rate) so that higher scores reflected better performance. Moreover, to account
      for differences in measurement scales, the standardized outcomes were rescaled
      according to their mean total standard deviations. Finally, the individual
      rescaled indicators of each year were summed to generate a combined outcome
      index. RESULTS: Mean cumulative observed mortality, morbidity, unplanned
      intensive care unit, and prolonged hospital stay rates were 1.8%, 23%, 6.6%, and
      7.4%, respectively. The combined outcome index scores showed a progressive
      improvement of performance during the study period, progressing from -3.48 in
      2005 to 2.87 in 2009. The combined outcome index was also used prospectively in a
      variable life-adjusted display chart to track down trends of practice variation
      in the last 6 months. CONCLUSIONS: The present analysis is proposed as a
      methodologic template for developing a risk-adjusted index combining four
      different outcomes. It aims at overcoming inherent limitations of outcomes when
      used individually for performance assessment. This or similar combined indexes
      may be effective instruments of internal clinical audit and could be incorporated
      along with process indicators in composite performance scores to more
      comprehensively evaluate the postoperative domain of our practice.

PMID- 21718856
TI  - Invited commentary.

PMID- 21718857
TI  - Endobronchial-ultrasound guided miniforceps biopsy of mediastinal and hilar
      lesions.
AB  - BACKGROUND: Linear array endobronchial ultrasound (EBUS) has greatly improved the
      diagnostic yield of transbronchial needle aspiration (TBNA) for the diagnosis of
      non-small cell lung carcinoma though its yield in granulomatous disease and
      lymphoproliferative disorders is less robust. The EBUS-miniforceps biopsy (MFB)
      uses miniforceps and the convex probe EBUS bronchoscope to obtain forceps
      biopsies of centrally located lesions under continuous ultrasound guidance. In
      this prospective study we evaluate the efficacy of this technique for diagnosing
      mediastinal and hilar abnormalities in patients with a low suspicion for non
      small cell lung carcinoma. METHODS: Patients presenting with mediastinal or hilar
      lymphadenopathy and a low likelihood of non-small cell lung carcinoma underwent
      EBUS-TBNA and EBUS-MFB of mediastinal and hilar abnormalities. The diagnostic
      yield EBUS-TBNA and EBUS-MFB was compared as was the combined yield of both
      techniques versus either technique alone. RESULTS: Between June 2008 and July
      2010, 50 patients underwent EBUS-TBNA and EBUS-MFB of 74 lymph node stations. The
      overall diagnostic yield of EBUS-TBNA and EBUS-MFB was 81% (60 of 74) and 91% (67
      of 74), respectively (p=0.09). When the 2 techniques were combined, the overall
      diagnostic yield was 97% (72 of 74) (p<0.001), which was significant when
      compared with EBUS-TBNA alone. No complications were observed as a result of EBUS
      MFB, and EBUS-MFB did not appear to significantly prolong the procedure.
      CONCLUSIONS: The EBUS-miniforceps biopsy is an effective, safe, and efficient
      method of obtaining histopathologic specimens from mediastinal and hilar
      abnormalities in patients with a low likelihood of non-small cell lung carcinoma,
      particularly when the technique is combined with EBUS-TBNA.

PMID- 21718858
TI  - Invited commentary.

PMID- 21718859
TI  - Invited commentary.

PMID- 21718860
TI  - Endoscopic management of idiopathic tracheal stenosis.
AB  - BACKGROUND: Idiopathic tracheal stenosis (ITS) is a rare condition representing a
      difficult therapeutic challenge. Endoscopic management is a therapeutic option
      but long-term results are not established. The aim of this retrospective
      multicenter study was to analyze long-term outcome after endoscopic management of
      ITS. METHODS: Nine institutions involved in interventional bronchoscopy were
      contacted and asked to identify ITS endoscopically treated. A standard form was
      used to report the main characteristics and long-term outcome after endoscopic
      management. RESULTS: Twenty-three patients, 96% women, aged 45+/-16 years, were
      endoscopically treated for ITS. Time between first symptoms and diagnosis was
      19+/-18 months. Bronchoscopy showed a weblike (61%) or complex (39%) stenosis,
      located in the upper part of the trachea, mainly in the cricoid area. Endoscopic
      treatment included mechanical dilation only (52%) or associated with laser or
      electrocoagulation (30%) and stent placement (18%). All procedures were
      efficient. The follow-up after endoscopic management was 41+/-34 months. The ITS
      recurrence occurred in 30% at 6 months, 59% at 2 years, and 87% at 5 years, with
      a delay of 14+/-16 months. The treatment of recurrence (n=13) included endoscopic
      management in 12 cases. CONCLUSIONS: Endoscopic management of ITS provides a safe
      and efficient therapeutic option but late recurrences are frequent and require
      long-term follow-up.

PMID- 21718861
TI  - Invited commentary.

PMID- 21718862
TI  - Lung transplantation and coronary artery disease.
AB  - BACKGROUND: Coronary artery disease (CAD) remains a relative contraindication to
      lung transplantation. We have offered lung transplantation and coronary
      revascularization to selected patients with discrete CAD and preserved left
      ventricular function. The purpose of this report is the following: (1) to examine
      the short-term and medium-term outcome of patients after coronary
      revascularization and lung transplantation; and (2) to compare the short-term and
      medium-term outcome of this cohort to a matched group of lung transplant
      recipients without CAD. METHODS: From January 2000 to March 2010, 27 patients
      with CAD underwent coronary revascularization and lung transplantation. The
      control group was matched based on age, diagnosis, lung allocation score, and
      type of procedure. RESULTS: Lung transplant recipients with CAD and the control
      group had similar incidence of primary graft dysfunction (grade III). The
      duration of mechanical ventilation, intensive care unit stay, and hospital stay
      were the same. At a mean follow-up of 3 years, the incidence of composite adverse
      cardiac events was similar in the 2 groups. CONCLUSIONS: Lung transplant
      recipients with CAD and the control group also had similar medium-term survival.
      Lung transplantation can be considered in patients with preexistent CAD with
      acceptable early and medium-term outcomes.

PMID- 21718863
TI  - Impact of anastomotic techniques on airway complications after lung transplant.
AB  - BACKGROUND: Airway complications are a source of morbidity and expense after lung
      transplant. Posttransplant stenosis can occur when the donor bronchus is rendered
      ischemic and is dependent upon collateral flow from the pulmonary capillary
      system. By shortening the donor bronchus, the tissue at risk for ischemia is
      reduced. In an effort to reduce airway complications, one surgeon at our
      institution began dividing the donor bronchus at the lobar carina. METHODS: This
      is a retrospective analysis of all transplanted patients over the 2-year period
      before and after the institution of the technique change. To adjust for
      covariates, we performed a propensity score analysis. Outcome endpoints were
      postoperative airway complications, specifically, the need for therapeutic
      bronchoscopy, dilation, stenting, or retransplant. RESULTS: After instituting the
      practice of dividing the bronchus at the lobar carina, the incidence of airway
      complication for the principle surgeon decreased from 13.2% (7 of 53) to 2.1% (1
      of 48), resulting in an improved freedom from airway complication for that
      surgeon. Compared with all transplants performed during this period, the modified
      anastomosis resulted in fewer airway complications: 2.1% (1 of 48) versus 8.2%
      (19 of 231). The propensity analysis matched the 48 patients who received the
      modified anastomosis with 48 patients who received the standard two ring length
      anastomosis by surgical colleagues. The modified anastomosis group had fewer
      required interventions for airway complications and had significantly better
      freedom from airway complication when followed over time. CONCLUSIONS: Decreasing
      the amount of potentially ischemic tissue implanted from the donor bronchus can
      reduce posttransplant airway complications.

PMID- 21718864
TI  - Pneumothorax recurrence after surgery in women: clinicopathologic characteristics
      and management.
AB  - BACKGROUND: Our aim was to study the clinical, surgical, and pathological
      characteristic of women with homolateral recurrence of pneumothorax despite
      previous surgery. METHODS: This study is a retrospective analysis of the clinical
      and pathological records of all consecutive women of reproductive age
      hospitalized in a thoracic surgery department for surgical treatment of
      pneumothorax recurrence despite previous surgery between 2000 and 2009. RESULTS:
      During the study period, 35 women were operated on. Their mean age was 37 years.
      Twenty-nine pneumothoraces (83%) were right sided. In 20 women, the recurrence
      occurred during the menstrual period. At initial surgery, 5 cases had been
      catamenial with evidence of thoracic endometriosis, 12 were catamenial with no
      evidence of endometriosis, 5 were noncatamenial with thoracic endometriosis, and
      13 were idiopathic. At repeat surgery the figures were 18, 4, 5, and 8 cases,
      respectively. Repeat operation was carried out by video-assisted thoracoscopy in
      13 cases, video-assisted minithoracotomy in 10, and standard thoracotomy in 12.
      Partial diaphragmatic resection was performed at repeat surgery in 16 patients
      (45.7%). Talc pleurodesis and pleural abrasion were carried out in 20 (57.1%) and
      15 patients (42.9%), respectively. No major morbidity was observed. After repeat
      surgery, hormonal treatment was prescribed in 24 cases. Median follow-up was 40
      months (range, 1.5 to 138 months). In 6 women, further homolateral recurrence of
      pneumothorax occurred (17.1%) and required surgery in 3 cases. CONCLUSIONS:
      Repeat surgery can be safely performed in women with recurrence of pneumothorax
      despite previous surgery, and frequently shows initially missed endometriosis.

PMID- 21718865
TI  - Extracorporeal membrane oxygenation in 5 patients with bronchial fistula with
      severe acute lung injury.
AB  - PURPOSE: The management of bronchial fistula associated with acute lung injury
      raises two major concerns: (1) high ventilation pressures are necessary for lung
      recruitment but detrimental for fistula healing, and (2) adequate lung
      recruitment is prevented by large air leak. Primary surgical closure of bronchial
      fistula should be attempted but is rarely successful during mechanical
      ventilation. We sought to evaluate the efficacy of extracorporeal membrane
      oxygenation associated with lung-protective ventilation in case of failure of
      conventional management. DESCRIPTION: Arteriovenous extracorporeal membrane
      oxygenation was initiated by femorofemoral cannulation. A stepwise increase of
      extracorporeal membrane oxygenation output and a decrease of mechanical
      ventilation settings were simultaneously performed, aiming at lung-protective
      ventilation. EVALUATION: During a 1-year period, this protocol management was
      used in 5 patients with refractory respiratory failure associated with bronchial
      fistula after thoracic operations. This strategy allowed fistula healing in 3
      patients. CONCLUSIONS: If correctly timed, extracorporeal membrane oxygenation
      can provide a therapeutic bridge to lung-protective ventilation and allow
      bronchial fistula healing in case of refractory respiratory failure.

PMID- 21718866
TI  - Invited commentary.

PMID- 21718867
TI  - An assay to monitor bivalirudin levels on cardiopulmonary bypass.
AB  - Anticoagulation therapy for cardiopulmonary bypass in patients with recently
      diagnosed heparin-induced thrombocytopenia can be particularly challenging.
      Although heparin is the standard of care, in these situations anticoagulation is
      achieved with alternative agents such as direct thrombin inhibitors. Therapeutic
      concentrations are difficult to assess with direct thrombin inhibitors, and their
      use is riddled with bleeding and thrombotic complications. We report the
      successful use of a specific chromogenic antifactor IIa assay in a patient with
      heparin-induced thrombocytopenia who received anticoagulation therapy with
      bivalirudin during cardiopulmonary bypass for coronary artery bypass graft
      surgery.

PMID- 21718868
TI  - Concomitant left ventricular assist device placement and cryoablation for
      treatment of ventricular tachyarrhythmias associated with heart failure.
AB  - Refractory ventricular tachyarrythmias (VTs) are potentially life-threatening
      rhythms in patients with cardiomyopathies, particularly when they result in
      hemodynamic instability. Here we report two cases of patients with intractable
      ventricular tachyarrythmias that were unresponsive to anti-arrhythmic medications
      and repeated catheter ablation, and for whom concomitant cryoablation and left
      ventricular assist device implantation was successfully performed. Both patients
      tolerated the procedure well with no complications and were free from ventricular
      tachyarrythmias postoperatively. Concomitant surgical ventricular ablation at the
      time of left ventricular assist device surgery may be a reasonable approach for
      this subset of patients as it provides excellent visualization and the ability to
      ablate both epicardial and endocardial sites.

PMID- 21718869
TI  - Impact of immediate aortic repair on early and midterm neurologic status in
      patients with acute type a aortic dissection complicated by cerebral
      malperfusion.
AB  - Surgical treatment for acute type A aortic dissection (AAD) complicated by
      cerebral malperfusion (CM) remains debatable. Worsening of neurologic symptoms
      and poor quality of life after immediate surgery continue to be cause for
      concern. We performed immediate aortic repair followed by early rehabilitation in
      10 patients with AAD complicated by CM. The early and midterm neurologic statuses
      were satisfactory. The immediate aortic repair did not have a negative impact on
      early and midterm neurologic condition in patients with AAD complicated by CM.

PMID- 21718870
TI  - Polypoid pseudomyxoma of ascending aorta after replacement with a Dacron graft.
AB  - We report a 58-year-old man who had a multi-lobulated pseudomyxomatous lesion in
      his ascending aorta 6 months after his root and ascending aorta was replaced by a
      Dacron graft.

PMID- 21718871
TI  - Aortic root vasculitis associated with Cogan's syndrome.
AB  - Cogan's syndrome is characterized by nonsyphilitic interstitial keratitis and an
      audiovestibular disorder resembling Meniere disease. We report a patient with
      progressive congestive heart failure due to massive aortic and mitral
      insufficiency coupled with aortitis leading to an ascending aortic aneurysm. The
      patient underwent successful aortic root replacement and mitral valve repair.

PMID- 21718872
TI  - Intermediate and early rupture of expanded polytetrafluoroethylene neochordae
      after mitral valve repair.
AB  - Neochordae construction using an expanded polytetrafluoroethylene suture is an
      accepted surgical technique to correct mitral regurgitation due to mitral valve
      prolapse. We report two cases of intermediate and early rupture of CV-5 expanded
      polytetrafluoroethylene neochordae after mitral valve repair. As a result of
      these cases, we now use CV-3 expanded polytetrafluoroethylene for neochordae
      construction with no failures.

PMID- 21718873
TI  - Computed tomography detects tissue formation in a stented engineered heart valve.
AB  - Tissue-engineered heart valves (TEHV) are being explored as an alternative to
      conventional heart valve prostheses. Using the classic tissue engineering
      paradigm, a stented tri-leaflet valve is fabricated. Subsequently, the construct
      is implanted into the pulmonary position in a sheep. Follow-up by means of
      computed tomography, magnetic resonance imaging, and echocardiography was used to
      assess tissue formation. After 4 weeks, the scaffold of the TEHV has degraded and
      new tissue is formed. However, small areas without tissue formation were present
      at macroscopic inspection. This phenomenon was only visible on computed
      tomographic images. Therefore, computed tomography appears a promising technique
      for in vivo follow-up of tissue formation in tissue-engineered heart valves.

PMID- 21718874
TI  - Catheter takedown in the management of the acutely failing Fontan circulation.
AB  - The acutely failing Fontan circulation requires urgent management to decompress
      the systemic venous pressures and augment cardiac output. This may involve the
      use of extracorporeal membrane oxygenation support to preserve life. Catheter
      based effective Fontan takedown is an alternative to surgery in these patients,
      who are acutely unstable, and offers the potential for an adjustable
      fenestration.

PMID- 21718875
TI  - Phrenic nerve palsy and Parsonage-Turner syndrome.
AB  - This report describes 2 symptomatic patients with phrenic nerve palsy due to
      Parsonage-Turner syndrome who were managed by diaphragmatic plication. The
      characteristics of the underlying syndrome are defined.

PMID- 21718876
TI  - Mediastinal teratoma and trichoptysis.
AB  - We report the case of a 22-year-old woman suffering from mature mediastinal
      teratoma, revealed by trichoptysis, which is an exceptional, but pathognomonic
      symptom of intrathoracic teratomas. Only eight cases of trichoptysis are
      reported, none of them involved a mediastinal localization. We present the
      endoscopic and radiologic presentation, its surgical management, and histologic
      particularities.

PMID- 21718877
TI  - Resection of a posterior mediastinal metastasis of colon cancer.
AB  - We report a resection of a posterior mediastinal metastasis of colon cancer. A 29
      year-old man who had undergone a right hemicolectomy and liver resection for
      ascending colon cancer with liver metastasis was referred to our hospital with
      the diagnosis of a solitary posterior mediastinal metastasis. Tumor extirpation
      with descending aorta replacement was performed. Five months after the operation,
      local recurrence developed in the posterior mediastinum, which was also resected.
      He has been recurrence-free for 5 years since the second procedure. In this case,
      the metastases were believed to have occurred through the thoracic duct.

PMID- 21718878
TI  - A giant unruptured aneurysm of the sinus of Valsalva together with ectasia of the
      left coronary artery.
AB  - A sinus of Valsalva aneurysm is defined as a dilatation of the aortic sinuses,
      between the aortic valve annulus and the sinotubular junction. They are rare and
      most frequently involve the right coronary sinus. We report a case of an
      unruptured giant sinus of Valsalva aneurysm in a patient associated with ectasia
      of the left main stem and left anterior descending coronary artery. The patient
      was successfully treated with aortic root replacement using a biologic conduit.

PMID- 21718879
TI  - Long-term survival in a rare case of malignant esophageal schwannoma cured by
      surgical excision.
AB  - A full account is presented of a 44-year-old woman with an extremely rare case of
      a malignant esophageal schwannoma that had been misdiagnosed as a leiomyoma 3
      years earlier. After surgical enucleation, the patient has survived for 6 years
      without any adjunctive treatment.

PMID- 21718880
TI  - Pseudoaneurysm and abscess of the left anterior descending coronary artery.

PMID- 21718881
TI  - Anomalous great cardiac vein draining into the superior vena cava.

PMID- 21718882
TI  - Aortosternal venous compression: innominate vein compression by the innominate
      artery.

PMID- 21718883
TI  - The completion Bentall procedure.
AB  - Patients that have undergone aortic valve replacement may subsequently present
      with an aortic root aneurysm, but with a normally functioning prosthetic valve.
      We describe our method of replacing the aortic root while retaining the existing
      aortic valve as the "completion Bentall procedure."

PMID- 21718884
TI  - Spring retractor: a new adjunct for aortic valve surgery.
AB  - We describe a new aortic retractor that is effective in maintaining aortic root
      geometry and providing for adequate intraoperative visual valve assessment, and
      therefore enables the surgeon to perform precise aortic valve repair or
      replacement procedures.

PMID- 21718885
TI  - Antibiotic sandwich patch for ventricular septal defect complicated by
      endocarditis.
AB  - Infective endocarditis in patients with ventricular septal defects can prove life
      threatening due to acute heart failure or septic embolization. Persistent
      postoperative risk is bacterial colonization of prosthetic material. We designed
      the Antibiotic Sandwich Patch to reduce this risk, using a double layer of
      autologous pericardium containing antibiotic powder. Five patients were managed
      with this technique for closure of ventricular septal defects complicated by
      acute infective endocarditis. No colonization of the patches occurred after a
      median follow up of 1.5 years. This technique reduced the risk of bacterial
      colonization of the antibiotic sandwich patch, offering an additional surgical
      option.

PMID- 21718886
TI  - Reconstruction of cervical esophagectomy defects using laryngotracheal bloc.
AB  - Surgical treatment of cervical esophagus cancers generally requires a cervical
      esophagectomy followed by a reconstruction of the removed segment of the upper
      digestive tract. We describe the use of laryngotracheal bloc for the
      reconstruction of a resected cervical esophageal defect. Three patients were
      submitted to this technique. All operations were successfully performed without
      major procedure-related complications. Ability to swallow was preserved. During a
      period of ten to twenty-four months of follow-up, all the patients have survived,
      and can resume a regular diet. The preliminary results show that laryngotracheal
      bloc is an excellent choice for the reconstruction of the cervical esophagus
      segment after cancer resections, offering patients fast rehabilitation, lower
      morbidity, and recovery of satisfactory swallowing function.

PMID- 21718887
TI  - Transcatheter valve therapy: a professional society overview from the American
      College of Cardiology Foundation and the Society of Thoracic Surgeons.

PMID- 21718888
TI  - Secondary cross-clamping and blood cardioplegia for refractory ventricular
      fibrillation.

PMID- 21718889
TI  - Blood conservation guidelines for pediatric patients.

PMID- 21718891
TI  - Vascular anomalies of the mediastinum.

PMID- 21718893
TI  - Myasthenia gravis and recurrent thymoma.

PMID- 21718895
TI  - Prox-1: a specific and sensitive marker for lymphatic endothelium in normal and
      diseased human tissues.

PMID- 21718897
TI  - Long-term survival of VATS versus open lobectomy.

PMID- 21718902
TI  - [The role of women in medical and scientific research in the 21st century: a need
      for debate].

PMID- 21718901
TI  - New trends in resuscitation.

PMID- 21718903
TI  - Imaging of pulmonary vein stenosis using multidimensional phase contrast magnetic
      resonance imaging (4-dimensional flow).

PMID- 21718904
TI  - Stroke intervention: catheter-based therapy for acute ischemic stroke.
AB  - The majority (>80%) of the three-quarters of a million strokes that will occur in
      the United States this year are ischemic in nature. The treatment of acute
      ischemic stroke is very similar to acute myocardial infarction, which requires
      timely reperfusion therapy for optimal results. The majority of patients with
      acute ischemic stroke do not receive any form of reperfusion therapy, unlike
      patients with acute myocardial infarction. Improving outcomes for acute stroke
      will require patient education to encourage early presentation, an aggressive
      expansion of qualified hospitals, and willing providers and early imaging
      strategies to match patients with their best options for reperfusion therapy to
      minimize complications.

PMID- 21718905
TI  - Percutaneous tricuspid valve replacement in congenital and acquired heart
      disease.
AB  - OBJECTIVES: This study sought to describe the first human series of percutaneous
      tricuspid valve replacements in patients with congenital or acquired tricuspid
      valve (TV) disease. BACKGROUND: Percutaneous transcatheter heart valve
      replacement of the ventriculoarterial (aortic, pulmonary) valves is established.
      Although there are isolated reports of transcatheter atrioventricular heart valve
      replacement (hybrid and percutaneous), this procedure has been less frequently
      described; we are aware of no series describing this procedure for TV disease.
      METHODS: We approached institutions with significant experience with the Melody
      percutaneous pulmonary valve (Medtronic, Inc., Minneapolis, Minnesota) to collect
      data where this valve had been implanted in the tricuspid position. Clinical and
      procedural data were gathered for 15 patients. Indications for intervention
      included severe hemodynamic compromise and perceived high surgical risk; all had
      prior TV surgery and significant stenosis and/or regurgitation of a bioprosthetic
      TV or a right atrium-to-right ventricle conduit. RESULTS: Procedural success was
      achieved in all 15 patients. In patients with predominantly stenosis, mean
      tricuspid gradient was reduced from 12.9 to 3.9 mm Hg (p < 0.01). In all
      patients, tricuspid regurgitation was reduced to mild or none. New York Heart
      Association functional class improved in 12 patients. The only major procedural
      complication was of third-degree heart block requiring pacemaker insertion in 1
      patient. One patient developed endocarditis 2 months after implant, and 1 patient
      with pre-procedural multiorgan failure did not improve and died 20 days after the
      procedure. The remaining patients have well-functioning Melody valves in the TV
      position a median of 4 months after implantation. CONCLUSIONS: In selected cases,
      patients with prior TV surgery may be candidates for percutaneous TV replacement.

PMID- 21718906
TI  - Transcatheter valve technology: a game changer!

PMID- 21718907
TI  - The impact of right coronary artery chronic total occlusion on clinical outcome
      of patients undergoing percutaneous coronary intervention for unprotected left
      main disease.
AB  - OBJECTIVES: The aim of the present study was to investigate whether right
      coronary artery chronic total occlusion (CTO) carries prognostic implications in
      patients undergoing drug-eluting stent-supported percutaneous coronary
      intervention (PCI) for unprotected left main disease (ULMD). BACKGROUND: No data
      exist on the prognostic implication of CTO in patients undergoing PCI for ULMD.
      METHODS: Prospective registry of consecutive patients undergoing PCI for ULMD.
      Patients with ST-segment elevation myocardial infarction were excluded. Primary
      endpoints were 6-month and long-term cardiac mortality. RESULTS: From January
      2004 to December 2009, 330 patients underwent PCI for ULMD. Of the 330 patients,
      78 (24%) had CTO of the right coronary artery, 22 (7%) had CTO of the left
      anterior descending artery, and 16 (5%) had CTO of the left circumflex artery.
      Patients with right coronary artery CTO had a higher risk profile compared with
      patients without right coronary artery CTO. The 6-month mortality rate was 12.8%
      in patients with right coronary artery CTO, and 3.6% in patients without right
      coronary artery CTO (p < 0.002), and the 3-year cardiac survival rate was 76.4 +/
      6.8% and 89.7 +/- 2.7% (p < 0.003), respectively. By multivariable analysis, the
      only 2 independent predictors of 3-year cardiac mortality were right coronary
      artery CTO (hazard ratio: 2.15, 95% confidence interval: 1.02 to 4.50; p = 0.043)
      and EuroSCORE (hazard ratio: 1.03, 95% confidence interval: 1.02 to 1.05; p <
      0.001). CONCLUSIONS: Right coronary artery CTO occurs frequently and is a
      significant predictor of mortality in patients with ULMD undergoing PCI.

PMID- 21718908
TI  - Impact of metabolic syndrome and diabetes on prognosis and outcomes with early
      percutaneous coronary intervention in the COURAGE (Clinical Outcomes Utilizing
      Revascularization and Aggressive Drug Evaluation) trial.
AB  - OBJECTIVES: Our purpose was to clarify the clinical utility of identifying
      metabolic syndrome (MetS) in patients with coronary artery disease (CAD).
      BACKGROUND: It is uncertain whether MetS influences prognosis in patients with
      CAD and whether the risk associated with MetS exceeds the risk associated with
      the sum of its individual components. METHODS: In a post hoc analysis, we
      compared the incidence of death or myocardial infarction (MI) in stable CAD
      patients in the COURAGE (Clinical Outcomes Utilizing Revascularization and
      Aggressive Drug Evaluation) trial according to the presence (+) or absence (-) of
      MetS and diabetes: Group A, -MetS/-diabetes; Group B, +MetS/-diabetes; Group C, 
      MetS/+diabetes; and Group D, +MetS/+diabetes. We explored which MetS components
      best predicted adverse outcomes and whether MetS had independent prognostic
      significance beyond its individual components. RESULTS: Of 2,248 patients, 61%
      had MetS and 34% diabetes. Risk for death or MI increased from Group A (14%) to
      Group D (25%, p < 0.001). Hypertension (hazard ratio [HR]: 1.30; 95% confidence
      interval [CI]: 0.98 to 1.71; p = 0.07), low high-density lipoprotein cholesterol
      (HR: 1.26; 95% CI: 1.03 to 1.55; p = 0.03), and elevated glucose (HR: 1.17; 95%
      CI: 0.96 to 1.47; p = 0.11) most strongly predicted death or MI. MetS was
      associated with an increased risk of death or MI (unadjusted HR: 1.41; 95% CI:
      1.15 to 1.73; p = 0.001). However, after adjusting for its individual components,
      MetS was no longer significantly associated with outcome (HR: 1.15; 95% CI: 0.79
      to 1.68; p = 0.46). Allocation to initial percutaneous coronary intervention did
      not affect the incidence of death or MI within any group. CONCLUSIONS: Among
      stable CAD patients in the COURAGE trial, the presence of MetS identified
      increased risk for death or MI, but MetS did not have independent prognostic
      significance after adjusting for its constituent components. The addition of
      early percutaneous coronary intervention to optimal medical therapy did not
      significantly reduce the risk of death or MI regardless of MetS or diabetes
      status. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug
      Evaluation [COURAGE]; NCT00007657).

PMID- 21718909
TI  - The lessons of COURAGE for the management of stable coronary artery disease.

PMID- 21718910
TI  - Impaired fasting glucose and the risk of incident diabetes mellitus and
      cardiovascular events in an adult population: MESA (Multi-Ethnic Study of
      Atherosclerosis).
AB  - OBJECTIVES: The purpose of the study was to assess the cardiovascular risk of
      impaired fasting glucose (IFG). BACKGROUND: The associations between IFG,
      incident type 2 diabetes mellitus (T2DM), and cardiovascular (CV) events remains
      unclear. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) study included
      participants who were 45 to 84 years or age and free of clinical CV disease at
      baseline (2000 to 2002). Type 2 DM was defined as fasting glucose >125 mg/dl or
      receiving antidiabetes medication at baseline and follow-up examinations; IFG was
      defined as no T2DM and fasting glucose 100 to 125 mg/dl. Cox proportional hazards
      analysis was used to assess the association between IFG and incident DM and also
      between IFG and incident CV events. RESULTS: Of 6,753 participants included in
      these analyses, 840 (12.7%) had T2DM and 940 (13.8%) had IFG at the baseline
      examination. During 7.5 years of follow-up, there were 418 adjudicated CV events.
      Type 2 DM was associated with an increased CV incidence in the univariate model
      (hazard ratio [HR]: 2.83, 95% confidence interval [CI]: 2.25 to 3.56, p < 0.0001)
      and multivariate model adjusted for demographics and traditional risk factors
      (HR: 1.87, 95% CI: 1.47 to 2.37, p < 0.0001) compared with subjects not having
      T2DM (IFG plus normal fasting glucose). Impaired fasting glucose was associated
      with increased incidence of T2DM (HR: 13.2, 95% CI: 10.8 to 16.2, p < 0.001) that
      remained after adjusting for demographics, highest educational level, physical
      activity, and body mass index (HR: 10.5, 95% CI: 8.4 to 13.1, p < 0.001) compared
      with normal fasting glucose. Impaired fasting glucose was associated with
      incident CV events in the univariate model (HR: 1.64, 95% CI: 1.26 to 2.14, p <
      0.001) but not in the full multivariate model (HR: 1.16, 95% CI: 0.88 to 1.52, p
      = 0.3) compared with normal fasting glucose. CONCLUSIONS: Having IFG was not
      independently associated with an increased short-term risk for incident CV
      events. These data reiterate the importance of intervention for persons with IFG
      to reduce their incidence of T2DM.

PMID- 21718911
TI  - Tachycardia-induced diastolic dysfunction and resting tone in myocardium from
      patients with a normal ejection fraction.
AB  - OBJECTIVES: The purpose of this study is to evaluate tachycardia-induced
      relaxation abnormalities in myocardium from patients with a normal ejection
      fraction. BACKGROUND: Diastolic dysfunction and left ventricular (LV) hypertrophy
      are closely linked. Tachycardia can induce heart failure symptoms in otherwise
      asymptomatic patients. To study the effects of tachycardia on myocardial
      contractility and relaxation, we evaluated the effects of increasing pacing rates
      in myocardial biopsy samples obtained from patients with a normal ejection
      fraction. METHODS: LV biopsy samples were obtained during coronary bypass
      surgery. Myocardial strip preparations were electrically paced at rates from 60
      to 180 beats/min. Diastolic resting tone was assessed by cross-bridge
      deactivation. Calcium transporting systems were functionally examined, and
      myofilament calcium sensitivity was studied. RESULTS: Incomplete relaxation
      developed in 7 preparations, with increased diastolic tension development at
      increasing pacing rates. This was absent in the remaining 7 preparations.
      Incomplete relaxation was found to be associated with increased LV mass and left
      atrial volume. Cross-bridge deactivation showed that these preparations also had
      a significant resting tone. Additional functional analyses suggest that
      incomplete relaxation is associated with disproportionately elevated cellular
      calcium loads due to a reduced sarcolemmal calcium extrusion reserve.
      CONCLUSIONS: Tachycardia-induced incomplete relaxation was associated with
      increased LV mass and left atrial volumes. We also found a disproportionately
      increased calcium load at high rates and a substantial resting tone due to
      diastolic cross-bridge cycling. These observations may play a role in reduced
      exercise tolerance and tachycardia-induced diastolic dysfunction.

PMID- 21718912
TI  - Abnormal calcium homeostasis: one mechanism in diastolic heart failure.

PMID- 21718913
TI  - Epicardial ablation of rotors suppresses inducibility of acetylcholine-induced
      atrial fibrillation in left pulmonary vein-left atrium preparations in a beagle
      heart failure model.
AB  - OBJECTIVES: The purpose of this study was to provide direct evidences that rotor
      ablation suppresses atrial fibrillation (AF) inducibility. BACKGROUND: Micro-re
      entrant wavefronts have been suggested to serve as sources of rapid activations
      during AF. Whether AF inducibility is suppressed by elimination of rotors remains
      unknown. METHODS: We used optical mapping to study Langendorff-perfused left
      pulmonary vein (PV)-left atrium (LA) preparations from 13 dogs with pacing
      induced heart failure. Atrial arrhythmias were induced by pacing and mapped
      during acetylcholine infusion (1 MUmol/l). Rotors were identified from optical
      recordings. Epicardial ablation was performed targeting the rotor anchoring sites
      in preparations with sustained (>10 min) or incessant spontaneous AF. Non-rotor
      ablation was performed in 4 preparations. Repeated pacing was performed to test
      the AF inducibility after ablation. RESULTS: Sustained AF (n = 12) and incessant
      spontaneous AF (n = 1) were induced after acetylcholine infusion. Pulmonary vein
      focal discharge was found in 9 preparations (9.2 +/- 4.2 beats/s), and rotor
      anchoring was found at the left superior PV-LA junction in 13 preparations (9.1
      +/- 4.6 beats/s) and at the ligament of Marshall-PV-LA junction in 1 preparation.
      Epicardial rotor ablation successfully inhibited the inducibility of sustained AF
      in 12 of 13 preparations (p < 0.01), including 4 with the maximal dominant
      frequency sites located on the PV-LA junctional rotor zones (direct elimination
      of mother rotors). The longest AF duration was shortened significantly by rotor
      ablation (Wilcoxon Z = 3.60, p = 0.002, n = 13), but not by non-rotor ablation
      (Wilcoxon Z = 1.00, p = 0.317, n = 4). CONCLUSIONS: Epicardial ablation of the
      rotor anchoring sites suppresses AF inducibility. The arrhythmogenicity at the
      maximal dominant frequency sites is directly/indirectly suppressed by the rotor
      ablation.

PMID- 21718914
TI  - Dark regions of no-reflow on late gadolinium enhancement magnetic resonance
      imaging result in scar formation after atrial fibrillation ablation.
AB  - OBJECTIVES: The aim of this study was to assess acute ablation injuries seen on
      late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) immediately
      post-ablation (IPA) and the association with permanent scar 3 months post
      ablation (3moPA). BACKGROUND: Success rates for atrial fibrillation catheter
      ablation vary significantly, in part because of limited information about the
      location, extent, and permanence of ablation injury at the time of procedure.
      Although the amount of scar on LGE MRI months after ablation correlates with
      procedure outcomes, early imaging predictors of scar remain elusive. METHODS:
      Thirty-seven patients presenting for atrial fibrillation ablation underwent high
      resolution MRI with a 3-dimensional LGE sequence before ablation, IPA, and 3moPA
      using a 3-T scanner. The acute left atrial wall injuries on IPA scans were
      categorized as hyperenhancing (HE) or nonenhancing (NE) and compared with scar
      3moPA. RESULTS: Heterogeneous injuries with HE and NE regions were identified in
      all patients. Dark NE regions in the left atrial wall on LGE MRI demonstrate
      findings similar to the "no-reflow" phenomenon. Although the left atrial wall
      showed similar amounts of HE, NE, and normal tissue IPA (37.7 +/- 13%, 34.3 +/-
      14%, and 28.0 +/- 11%, respectively; p = NS), registration of IPA injuries with
      3moPA scarring demonstrated that 59.0 +/- 19% of scar resulted from NE tissue,
      30.6 +/- 15% from HE tissue, and 10.4 +/- 5% from tissue identified as normal.
      Paired t-test comparisons were all statistically significant among NE, HE, and
      normal tissue types (p < 0.001). Arrhythmia recurrence at 1-year follow-up
      correlated with the degree of wall enhancement 3moPA (p = 0.02). CONCLUSIONS:
      Radiofrequency ablation results in heterogeneous injury on LGE MRI with both HE
      and NE wall lesions. The NE lesions demonstrate no-reflow characteristics and
      reveal a better predictor of final scar at 3 months. Scar correlates with
      procedure outcomes, further highlighting the importance of early scar prediction.

PMID- 21718915
TI  - Vitamin D status is associated with arterial stiffness and vascular dysfunction
      in healthy humans.
AB  - OBJECTIVES: The primary objective of this study was to elucidate mechanisms
      underlying the link between vitamin D status and cardiovascular disease by
      exploring the relationship between 25-hydroxyvitamin D (25-OH D), an established
      marker of vitamin D status, and vascular function in healthy adults. BACKGROUND:
      Mechanisms underlying vitamin D deficiency-mediated increased risk of
      cardiovascular disease remain unknown. Vitamin D influences endothelial and
      smooth muscle cell function, mediates inflammation, and modulates the renin
      angiotensin-aldosterone axis. We investigated the relationship between vitamin D
      status and vascular function in humans, with the hypothesis that vitamin D
      insufficiency will be associated with increased arterial stiffness and abnormal
      vascular function. METHODS: We measured serum 25-OH D in 554 subjects.
      Endothelial function was assessed as brachial artery flow-mediated dilation, and
      microvascular function was assessed as digital reactive hyperemia index. Carotid
      femoral pulse wave velocity and radial tonometry-derived central augmentation
      index and subendocardial viability ratio were measured to assess arterial
      stiffness. RESULTS: Mean 25-OH D was 31.8 +/- 14 ng/ml. After adjustment for age,
      sex, race, body mass index, total cholesterol, low-density lipoprotein,
      triglycerides, C-reactive protein, and medication use, 25-OH D remained
      independently associated with flow-mediated vasodilation (beta = 0.1, p = 0.03),
      reactive hyperemia index (beta = 0.23, p < 0.001), pulse wave velocity (beta = 
      0.09, p = 0.04), augmentation index (beta = -0.11, p = 0.03), and subendocardial
      viability ratio (beta = 0.18, p = 0.001). In 42 subjects with vitamin D
      insufficiency, normalization of 25-OH D at 6 months was associated with increases
      in reactive hyperemia index (0.38 +/- 0.14, p = 0.009) and subendocardial
      viability ratio (7.7 +/- 3.1, p = 0.04), and a decrease in mean arterial pressure
      (4.6 +/- 2.3 mm Hg, p = 0.02). CONCLUSIONS: Vitamin D insufficiency is associated
      with increased arterial stiffness and endothelial dysfunction in the conductance
      and resistance blood vessels in humans, irrespective of traditional risk burden.
      Our findings provide impetus for larger trials to assess the effects of vitamin D
      therapy in cardiovascular disease.

PMID- 21718916
TI  - Cholesterol drugs reverse tendon xanthomas.

PMID- 21718917
TI  - President's page: The global college of cardiology: it's a small world after all.

PMID- 21718918
TI  - Validated smoking cessation and prognosis in patients with stable coronary heart
      disease.

PMID- 21718919
TI  - We need further studies for the development of "optimized antiplatelet therapy"
      based on ethnicity.

PMID- 21718921
TI  - Vasovagal syncope as a cause of syncope in long-QT syndrome.

PMID- 21718923
TI  - Surgical ablation for atrial fibrillation: not all energy sources are created
      equal.

PMID- 21718925
TI  - Introduction.

PMID- 21718926
TI  - Management of simultaneous common and internal carotid artery occlusive disease
      in the endovascular era.
AB  - Combined or tandem lesions of the common carotid artery and the ipsilateral
      carotid bifurcation are uncommon and the management of patients with this disease
      pattern can be challenging. The development of endovascular techniques has
      contributed a variety of options for managing these combined lesions; either as
      part of a hybrid approach (carotid endarterectomy and common carotid artery
      stent) or with stenting alone for both lesions. In this article, we review the
      technique and results of managing carotid revascularization in the context of
      tandem common carotid and internal carotid artery lesions in the endovascular
      era.

PMID- 21718927
TI  - Carotid endarterectomy: still the standard of care for carotid bifurcation
      disease.
AB  - Current treatment guidelines of symptomatic and asymptomatic carotid stenosis are
      based on studies performed over a decade ago. Since that time, significant
      advances have been made in medical management, namely high dose statin therapy
      and improved antiplatelet agents, and in carotid interventions, namely the advent
      of carotid artery stenting. Especially with carotid stenting, the technology has
      grown by leaps and bounds and continues to advance at a rapid pace. These
      advances have necessitated new studies to compare these treatments with the gold
      standard of carotid endarterectomy. In asymptomatic patients, the current data
      does not justify medical management alone for severe (>80%) carotid stenosis.
      Furthermore, in both asymptomatic and symptomatic patients current studies have
      failed to demonstrate equivalence of CAS to CEA for significant carotid stenosis.
      Clearly additional studies comparing CAS, CEA, and medical management are needed
      to further clarify this issue. In the future, advances in CAS technology and
      techniques may greatly expand the role of CAS beyond its current role in certain
      high-risk patient subsets. However, for the time being CEA still remains the gold
      standard for carotid intervention.

PMID- 21718928
TI  - Role of carotid stenting in management of carotid bifurcation disease: was the
      revolution overstated?
AB  - At its advent, carotid artery stenting (CAS) was widely touted by some as a
      revolution in the revascularization of severe carotid artery disease, destined to
      replace carotid endarterectomy (CEA). However, 15 years after the early phases of
      CAS, it still has only a limited role in carotid therapy in the US. This article
      will explore the reasons why, which are related to expert operator availability,
      early trials (largely EU based) that did not support the safety of CAS but which
      were confounded by a variety of factors which severely limited a true assessment
      of CAS outcomes, mandatory time-lines involved with regulatory approval,
      technique and patient selection, and Medicare non-coverage for the multiple FDA
      approved devices except for a very select population of patients. The recent
      publication of the CREST study, and the subsequent FDA Devices Panel presentation
      of additional analyses, demonstrates equivalent safety and long-term stroke
      prevention efficacy. This, combined with the adjunct morbidity associated with
      CEA including cranial nerve injury and excess incisional site complications,
      suggests that, assuming FDA and CMS approvals, that CAS is poised to have a
      greater place in the management of the carotid patient.

PMID- 21718929
TI  - Treatment of vertebral disease: appropriate use of open and endovascular
      techniques.
AB  - Vertebral artery disease is an often underdiagnosed and undertreated cause of
      posterior circulation ischemia. Revascularization of the vertebral circulation
      should be considered in patients refractory to medical therapy. Surgical and
      endovascular techniques are discussed and reviewed in the context of the location
      and type of vertebral artery disease.

PMID- 21718930
TI  - Open and endovascular management of subclavian and innominate arterial pathology.
AB  - Innominate and subclavian artery lesions run a wide spectrum of disease
      manifestation and treatment options. Since the first surgical treatment, multiple
      variances have been attempted with the desire to maintain high long-term patency
      rates while reducing perioperative morbidity and mortality. The advent of
      endovascular procedures in the 1970s provided the opportunity to seek alternative
      treatment options, but the fear of serious neurologic sequela stalled the
      adoption of these new techniques. The advancement in endovascular techniques and
      technology, along with proven clinical success and decreased morbidity and
      mortality, has led to their adoption as the first-line treatment.

PMID- 21718931
TI  - Diagnosing and treating atypical arterial pathologies of aortic arch vessels:
      dissection and fibromuscular dysplasia.
AB  - Although rare, pathologies of the aortic arch vessels can result in devastating
      sequelae. This article will address two of these pathologies, fibromuscular
      dysplasia and arterial dissection, along with diagnosis and treatment options.

PMID- 21718932
TI  - Endovascular management of patients with Takayasu arteritis: stents versus stent
      grafts.
AB  - Our objective was to report the experience of endovascular therapy to treat
      patients with Takayasu arteritis (TA) and evaluate outcomes. A review was
      undertaken of TA patients treated with endovascular means during a 9-year (2004
      to 2011) period. Patients were diagnosed using the American College of
      Rheumatology criteria and classified, based on angiographic criteria, using the
      Numano's Classification. The primary assessment of our analysis included patency
      of stent and stentgrafts. The secondary outcome measures included technical
      success, secondary interventions, and any periprocedural complications. A total
      of 25 arteritis patients were identified of which 14 patients had confirmed TA
      and were treated. Open surgical procedures were used in six patients, while the
      remaining eight underwent pure endovascular procedures or hybrid procedures, of
      which four had follow-up beyond 1 year. All four patients (all female), underwent
      six primary and five secondary vascular interventions. All lesions were stenotic
      in nature and the majority of patients (n = 3) had angiographic findings
      consistent with a combination of type I and type IV disease. Two abdominal stent
      grafts, one carotid stent, one innominate stent, one vertebral stent, one
      superior mesenteric stent, and bilateral renal stents were placed. Technical
      success was 100%, with the stent grafts staying patent longer than bare metal
      stents and patients with stent grafts undergoing fewer secondary interventions as
      opposed to those who had uncovered stents. Historically endovascular treatment of
      TA has been associated with poor outcomes with respect to patency. Newer
      endovascular techniques have allowed the use of alternatives methods that appear
      to be associated with better results. The use of stent grafts over uncovered
      stent will likely mitigate the risk of in-stent restenosis and occlusions.

PMID- 21718933
TI  - Choosing the appropriate intervention for symptomatic and asymptomatic carotid
      disease in the era of multiple therapies: integration of risk profile and
      technical data.
AB  - With rapid evolution of endovascular techniques, carotid artery stenting has
      emerged as an alternative to carotid endarterectomy. Several investigations have
      been performed that examine the roles of carotid endarterectomy and carotid
      artery stenting and some trials have sought to compare the two treatment
      modalities. There have also been advances in the understanding of optimal medical
      management of carotid artery stenosis. The obvious question that arises is what
      is the most appropriate treatment option for patients with symptomatic and
      asymptomatic carotid artery stenosis? The answer is not straightforward and
      requires an understanding of differential outcomes in select subgroups. A review
      of the major studies, including some of the most recent trials, will help to
      elucidate the optimal therapy.

PMID- 21718934
TI  - Review of new clinical applications of radiometal labeled radiopharmaceuticals.

PMID- 21718935
TI  - Radiopharmaceutical considerations on bone seeker uptake: should we learn from
      therapeutical targets of bisphosphonates?

PMID- 21718936
TI  - Preparation and in vivo biological investigations on a novel radioligand for bone
      scanning: technetium-99m-labeled zoledronic acid derivative.
AB  - INTRODUCTION: To enable imaging at an earlier time after injection, a
      radiopharmaceutical with higher affinity for bone, larger ratio of bone-to-soft
      tissue uptake and more rapid clearance from blood is required. The nature of
      diphosphonic acid is a key factor to determine the advantages of the
      radiopharmaceuticals. The purpose of this study is to optimize the linker chain
      between the imidazolyl and geminal diphosphonate group in the zoledronic acid
      (ZL) to develop novel single photon emission computed tomography (SPECT) bone
      imaging agent. METHODS: A novel ZL derivative, 1-hydroxy-3-(1H-imidazol-1
      yl)propane-1,1-diyldiphosphonic acid (IPrDP), was successfully prepared and
      labeled with (99m)Tc in a high labeling yield. Biodistribution of (99m)Tc-IPrDP
      and (99m)Tc-ZL in normal mice were studied and compared. SPECT bone scanning was
      performed on the rabbit and a series of dynamic and static images were recorded
      by Philips SKY Light emission computed tomography. RESULTS: In the
      biodistribution studies, (99m)Tc-IPrDP exhibits significant advantages on the
      bone resorption and the clearance from soft tissues compared with (99m)Tc-ZL.
      Kinetics of blood clearance in mice showed that T(1/2alpha) and T(1/2beta) of
      (99m)Tc-IPrDP were 1.47 min and 46.47 min, while those of (99m)Tc-ZL were 2.28
      and 52.63 min respectively. Excellent images of the rabbit skeleton can be
      quickly obtained for (99m)Tc-IPrDP, which was faster than (99m)Tc-ZL and the
      clinically widely used bone imaging agent (99m)Tc-MDP (technetium-99m labeled
      with methylenediphosphonate). CONCLUSIONS: (99m)Tc-IPrDP possesses excellent
      characteristics for the potential application as a novel bone scanning agent.

PMID- 21718937
TI  - Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as
      a bone scintigraphy agent.
AB  - INTRODUCTION: (68)Ga is a radionuclide of great interest as a positron emitter
      for positron emission tomography (PET). To develop a new bone-imaging agent with
      radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was
      chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which
      has a high affinity for bone, was prepared and evaluated. Although we are
      interested in developing (68)Ga-labeled bone imaging agents for PET, in these
      initial studies (67)Ga was used because of its longer half-life. METHODS: DOTA
      conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2
      (4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). (67)Ga-DOTA-Bn
      SCN-HBP was prepared by coordination with (67)Ga, and its in vitro and in vivo
      evaluations were performed. RESULTS: (67)Ga-DOTA-Bn-SCN-HBP was prepared with a
      radiochemical purity of over 95% without purification. (67)Ga-DOTA-Bn-SCN-HBP had
      great affinity for hydroxyapatite in binding assay. In biodistribution
      experiments, (67)Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly
      observed in tissues other than bone. Pretreatment of an excess amount of
      alendronate inhibited the bone accumulation of (67)Ga-DOTA-Bn-SCN-HBP.
      CONCLUSIONS: (67)Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics
      as a bone-imaging agent. These findings should provide useful information on the
      drug design of bone imaging agents for PET with (68)Ga.

PMID- 21718938
TI  - Dose-on-demand of diverse 18F-fluorocholine derivatives through a two-step
      microfluidic approach.
AB  - INTRODUCTION: The validation and confirmation of clinical usefulness of new and
      known positron emission tomography (PET) tracers require stable production routes
      and simple and robust radiochemical procedures. Microfluidic technologies are
      regarded as an approach that could allow an unprecedented flexibility and
      productivity in PET radiopharmaceutical research. In this work, we will show how
      a commercially available microfluidic system can be used for a sequential and
      repeatable radiosynthesis of three different fluorocholine analogues currently
      under investigation as tumor tracers. METHODS: Advion microfluidic system was
      used for performing the synthesis and purification of [(18)F]fluoromethyl,
      [(18)F]fluoroethyl or [(18)F]fluoropropyl choline employing a two-step approach,
      starting from the corresponding alkyl-ditosylate and reacting the
      [(18)F]fluorotosylate obtained in the first step with neat dimethylethanolamine.
      The purification was obtained using a recyclable SPE cartridge set. RESULTS: The
      three products, fluoromethylcholine, fluoroethylcholine and fluoropropylcholine,
      were obtained in good to optimum yields (22%-54% decay corrected) with a 15-min
      procedure. The production could be restarted several times for producing each one
      of the tracers without decrease in yields and purities, in accordance with a dose
      on-demand (DOD) approach. The final products were formulated in isotonic saline
      solution. CONCLUSION: The described approach gives a proof of principle of the
      enhanced productivity obtainable using a microfluidic approach; in particular,
      the possibility to produce the reported tracers in a DOD fashion following a
      homogeneous synthetic and purification approach will foster further studies on
      the clinical evaluation of the best fluorocholine analogue for prostate cancer
      imaging without biasing for differences in radiochemical approach.

PMID- 21718939
TI  - Fully automated one-pot radiosynthesis of O-(2-[18F]fluoroethyl)-L-tyrosine on
      the TracerLab FX(FN) module.
AB  - INTRODUCTION: An efficient fully automated method for the radiosynthesis of
      enantiomerically pure O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) using the
      GE TracerLab FX(FN) synthesis module via the O-(2-tosyloxyethyl)-N-trityl-L
      tyrosine tert-butylester precursor has been developed. METHODS: The
      radiolabelling of [(18)F]FET involved a classical [(18)F]fluoride nucleophilic
      substitution performed in acetonitrile using potassium carbonate and Kryptofix
      222, followed by acid hydrolysis using 2N hydrochloric acid. RESULTS: [(18)F]FET
      was produced in 35+/-5% (n=22) yield non-decay-corrected (55+/-5% decay
      corrected) and with radiochemical and enantiomeric purity of >99% with a specific
      activity of >90 GBq/MUmol after 63 min of radiosynthesis including HPLC
      purification and formulation. CONCLUSION: The automated radiosynthesis provides
      high and reproducible yields suitable for routine clinical use.

PMID- 21718940
TI  - Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine based on a cartridge purification
      method.
AB  - INTRODUCTION: O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is widely used as a
      positron emission tomography tracer for brain tumors. Usually, a high-performance
      liquid chromatography (HPLC) purification at the end of the two-step synthesis is
      applied. In this work, we report an automatic radiosynthesis of FET with a
      purification procedure based on standard cartridges. METHODS: O-(2
      [(18)F]fluoroethyl)-L-tyrosine was prepared by [(18)F]fluoroethylation of L
      tyrosine by a two-step synthesis using a modified [(11)C]methionine module
      (Nuclear Interface). In the first reaction step, we synthesized
      [(18)F]fluoroethyltosylate starting from [(18)F]fluoride. After a purification
      step, L-tyrosine was [(18)F]fluoroethylated with [(18)F]fluoroethyltosylate. The
      final reaction mixture was purified by means of solid phase extraction. The FET
      was trapped on an SCX cartridge, eluted with saline solution and trapped again on
      an HRX cartridge. For a second purification step, the FET was eluted from the HRX
      cartridge with ammonium acetate buffer and collected on two SCX cartridges
      followed by a washing step with water. The final product was eluted with saline
      solution and neutralised with 450 MUl NaHCO(3) solution (8.4%). RESULTS: The
      synthesis was finished after 50 min and delivered the FET in a range of 3-16 GBq.
      The synthesis typically yielded 41% (21 experiments) of FET (d.c.) without an
      HPLC purification step. The radiochemical purity ranged between 97% and 100%.
      CONCLUSION: We present a radiosynthesis of FET where the usually used HPLC
      purification procedure has been substituted by a purification step based on
      standard cartridges. This method is useful for automatic modules without an
      expensive HPLC purification unit and for the routine production of FET.

PMID- 21718941
TI  - The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy
      arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU,
      [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy.
AB  - INTRODUCTION: We and others have previously reported a four-step radiosynthesis
      of a series of 2'-deoxy-2'-[(18)F]fluoro-5-substituted-1-beta-D
      arabinofuranosyluracil derivatives including [(18)F]FAU, [(18)F]FEAU,
      [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU as thymidine derivatives
      for tumor proliferation and/or reporter gene expression imaging with positron
      emission tomography (PET). Although the radiosynthesis has been proven to be
      reproducible and efficient, this complicated multistep reaction is difficult to
      incorporate into an automated cGMP-compliant radiosynthesis module for routine
      production. Recently, we have developed a simple and efficient one-pot method for
      routine production of [(18)F]FMAU. In this study, we studied the feasibility of
      radiosynthesizing [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU
      and [(18)F]FIAU using this newly developed method. METHODS: Similar to the
      radiosynthesis of [(18)F]FMAU, 5-substituted 2'-[(18)F]fluoro-2'-deoxy
      arabinofuranosyluracil derivatives ([(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU,
      [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU) were synthesized in one-pot
      radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS.
      RESULTS: This one-pot radiosynthesis method could be used to produce [(18)F]FAU,
      [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU. The overall
      radiochemical yields of these tracers varied from 4.1%+/-0.8% to 10.1%+/-1.9%
      (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150
      min from the end of bombardment, and the radiochemical purity was >99%.
      CONCLUSIONS: The improved radiosyntheses of [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU,
      [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU have been achieved with reasonable
      yields and high purity using a multistep one-pot method. The synthetic time has
      been reduced, and the reaction procedures have been significantly simplified. The
      success of this approach may make PET tracers [(18)F]FAU, [(18)F]FEAU,
      [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU more accessible for
      preclinical and clinical research.

PMID- 21718942
TI  - Analysis of metabolism of 6FDG: a PET glucose transport tracer.
AB  - INTRODUCTION: We are developing (18)F-labeled 6-fluoro-6-deoxy-D-glucose
      ([(18)F]6FDG) as a tracer of glucose transport. As part of this process it is
      important to characterize and quantify putative metabolites. In contrast to the
      ubiquitous positron emission tomography (PET) tracer (18)F-labeled 2-fluoro-2
      deoxy-D-glucose ([(18)F]2FDG) which is phosphorylated and trapped
      intracellularly, the substitution of fluorine for a hydroxyl group at carbon-6 in
      [(18)F]6FDG should prevent its phosphorylation. Consequently, [(18)F]6FDG has the
      potential to trace the transport step of glucose metabolism without the
      confounding effects of phosphorylation and subsequent steps of metabolism. Herein
      the focus is to determine whether, and the degree to which, [(18)F]6FDG remains
      unchanged following intravenous injection. METHODS: Biodistribution studies were
      performed using 6FDG labeled with (18)F or with the longer-lived radionuclides
      (3)H and (14)C. Tissues were harvested at 1, 6, and 24 h following intravenous
      administration and radioactivity was extracted from the tissues and analyzed
      using a combination of ion exchange columns, high-performance liquid
      chromatography, and chemical reactivity. RESULTS: At the 1 h time-point, the vast
      majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood
      was identified as 6FDG. At the 6-h and 24-h time points, there was evidence of a
      minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D
      sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. CONCLUSION: On the time
      scale typical of PET imaging studies radioactive metabolites of [(18)F]6FDG are
      negligible.

PMID- 21718943
TI  - In vivo biodistribution and accumulation of 89Zr in mice.
AB  - INTRODUCTION: The present investigation focuses on the chemical and biological
      fate of (89)Zr in mice. Electrophoreses of (89)Zr solvated or chelated in
      different conditions are here presented. The biological fate of mice injected
      with [(89)Zr]Zr-oxalate, [(89)Zr]Zr-chloride, [(89)Zr]Zr-phosphate, [(89)Zr]Zr
      desferrioxamine and [(89)Zr]Zr-citrate is studied with the biodistribution, the
      clearances and positron emission tomography images. A special focus is also given
      regarding the quality of (89)Zr bone accumulation. METHODS: Electrophoreses were
      carried out on chromatography paper and read by gamma counting. Then, the
      solutions were intravenously injected in mice, imaged at different time points
      and sacrificed. The bones, the epiphysis and the marrow substance were separated
      and evaluated with gamma counts. RESULTS: The clearances of [(89)Zr]Zr-chloride
      and [(89)Zr]Zr-oxalate reached 20% of injected dose (ID) after 6 days whereas
      [(89)Zr]Zr-phosphate was only 5% of ID. [(89)Zr]Zr-citrate and [(89)Zr]Zr-DFO
      were noticeably excreted after the first day postinjection (p.i.). [(89)Zr]Zr
      chloride and [(89)Zr]Zr-oxalate resulted in a respective bone uptake of ~15% ID/g
      and~20% ID/g at 8 h p.i. with minor losses after 6 days. [(89)Zr]Zr-citrate bone
      uptake was also observed, but [(89)Zr]Zr-phosphate was absorbed in high amounts
      in the liver and the spleen. The marrow cells were insignificantly radioactive in
      comparison to the calcified tissues. CONCLUSION: Despite the complexity of Zr
      coordination, the electrophoretic analyses provided detailed evidences of Zr
      charges either as salts or as complexes. This study also shows that weakly
      chelated, (89)Zr is a bone seeker and has a strong affinity for phosphate.

PMID- 21718944
TI  - The synthesis and evaluation of N1-(4-(2-[18F]-fluoroethyl)phenyl)-N8
      hydroxyoctanediamide ([18F]-FESAHA), a PET radiotracer designed for the
      delineation of histone deacetylase expression in cancer.
AB  - INTRODUCTION: Given the significant utility of suberoylanilide hydroxamic acid
      (SAHA) in chemotherapeutic protocols, a PET tracer that mimics the histone
      deacetylase (HDAC) inhibition of SAHA could be a valuable tool in the diagnosis,
      treatment planning and treatment monitoring of cancer. Here, we describe the
      synthesis, characterization and evaluation of N(1)-(4-(2-[(18)F]
      fluoroethyl)phenyl)-N(8)-hydroxyoctanediamide ([(18)F]-FESAHA), a PET tracer
      designed for the delineation of HDAC expression in cancer. METHODS: FESAHA was
      synthesized and biologically characterized in vivo and in vitro. [(18)F]-FESAHA
      was then synthesized in high radiochemical purity, and the logP and serum
      stability of the radiotracer were determined. In vitro cellular uptake
      experiments and acute biodistribution and small-animal PET studies were performed
      with [(18)F]-FESAHA in mice bearing LNCaP xenografts. RESULTS: [(18)F]-FESAHA was
      synthesized in high radiochemical purity via an innovative one-pot procedure.
      Enzymatic inhibition assays illustrated that FESAHA is a potent HDAC inhibitor,
      with IC(50) values from 3 nM to 1.7 MUM against the 11 HDAC subtypes. Cell
      proliferation experiments revealed that the cytostatic properties of FESAHA very
      closely resemble those of SAHA in both LNCaP cells and PC-3 cells. Acute
      biodistribution and PET imaging experiments revealed tumor uptake of [(18)F]
      FESAHA and substantially higher values in the small intestine, kidneys, liver and
      bone. CONCLUSION: The significant non-tumor background uptake of [(18)F]-FESAHA
      presents a substantial obstacle to the use of the radiotracer as an HDAC
      expression imaging agent. The study at hand, however, does present a number of
      lessons critical to both the synthesis of hydroxamic acid containing PET
      radiotracers and imaging agents aimed at delineating HDAC expression.

PMID- 21718945
TI  - Influence of an aliphatic linker between DOTA and synthetic Z(HER2:342) Affibody
      molecule on targeting properties of the (111)In-labeled conjugate.
AB  - INTRODUCTION: Affibody molecules are small (~6.5 kDa) scaffold proteins suitable
      for radionuclide imaging of tumor-associated molecular targets. Site-specific
      labeling of Affibody molecules made by peptide synthesis can be achieved by
      coupling a chelator to N-terminus in the last synthesis step. The goal of this
      study was to evaluate the influence of a 6-aminohexanoic linker between DOTA and
      Z(HER2:342) on targeting properties of (111)In-labeled conjugate. METHODS: A DOTA
      conjugated 6-aminohexanoic linker-containing variant of Z(HER2:342) (ABY-003) was
      produced by peptide synthesis, and the in vitro binding affinity, specificity and
      cellular processing were evaluated. The biodistribution of (111)In-ABY-003 in
      normal mice was compared to (111)In-ABY-002 (DOTA-Z(HER2:342-pep2)) lacking the
      linker. Tumor-targeting properties of (111)In-ABY-003 were evaluated in mice
      bearing HER2-expressing xenografts. RESULTS: The dissociation constant of ABY-003
      was in the low picomolar range, slightly higher than for ABY-002. (111)In-ABY-003
      bound specifically to HER2-expressing cells in vitro. The cellular retention was
      efficient but slightly worse than for (111)In-ABY-002. In normal mice, the
      clearance of (111)In-ABY-003 from blood and other tissues was slightly but
      significantly faster compared to (111)In-ABY-002. Targeting of HER2-expressing
      xenografts by (111)In-ABY-003 was receptor-specific. Due to faster clearance, the
      tumor-to-blood ratio for (111)In-ABY-003 at 4 h postinjection was improved
      compared to (111)In-ABY-002. The capacity of (111)In-ABY-003 to visualize HER2
      expressing tumors was confirmed by gamma camera imaging. CONCLUSIONS: A 6
      aminohexanoic linker between the DOTA chelator and N-terminus of synthetic
      Z(HER2:342) had a measurable effect on affinity, cellular retention of
      radioactivity and blood clearance. The linker might be used for modulation of
      targeting properties of Affibody molecules.

PMID- 21718946
TI  - Evaluation of the P-glycoprotein- and breast cancer resistance protein-mediated
      brain penetration of 11C-labeled topotecan using small-animal positron emission
      tomography.
AB  - INTRODUCTION: Topotecan (TPT) is a camptothecin derivative and is an anticancer
      drug working as a topoisomerase-I-specific inhibitor. But TPT cannot penetrate
      through the blood-brain barrier. In this study, we synthesized a new positron
      emission tomography (PET) probe, [(11)C]TPT, to evaluate the P-glycoprotein (Pgp)
      and breast cancer resistance protein (BCRP)-mediated brain penetration of
      [(11)C]TPT using small-animal PET. METHODS: [(11)C]TPT was synthesized by the
      reaction of a desmethyl precursor with [(11)C]CH(3)I. In vitro study using
      [(11)C]TPT was carried out in MES-SA and doxorubicin-resistant MES-SA/Dx5 cells
      in the presence or absence of elacridar, a specific inhibitor for Pgp and BCRP.
      The biodistribution of [(11)C]TPT was determined using small-animal PET and the
      dissection method in mice. RESULTS: The transport of [(11)C]TPT to the
      extracellular side was determined in MES-SA/Dx5 cells exhibiting the expressions
      of Pgp and BCRP at high levels. This transport was inhibited by coincubation with
      elacridar. In Mdr1a/b(-/-)Bcrp1(-/-) mice, PET results indicated that the brain
      uptake of [(11)C]TPT was about two times higher than that in wild-type mice.
      Similarly, the brain penetration of [(11)C]TPT in wild-type mice was increased by
      treatment with elacridar. The radioactivity in the brain of elacridar-treated
      mice was maintained at a certain level after the injection of [(11)C]TPT,
      although the radioactivity in the blood decreased with time. CONCLUSIONS: We
      demonstrated the increase of brain penetration of [(11)C]TPT by deficiency and
      inhibition of Pgp and BCRP functions using small-animal PET in mice.

PMID- 21718947
TI  - Tumor targeting using 67Ga-DOTA-Bz-folate--investigations of methods to improve
      the tissue distribution of radiofolates.
AB  - INTRODUCTION: Use of folic acid radioconjugates for folate receptor (FR)
      targeting is a promising strategy for imaging purposes as well as for potential
      therapy of cancer and inflammatory diseases due to the frequent FR overexpression
      found on cancer cells and activated macrophages. Herein, we report on preclinical
      results using a novel DOTA-Bz-EDA-folate conjugate radiolabeled with [(67)Ga]
      gallium. METHODS: DOTA-Bz-EDA-folate was prepared by conjugation of
      ethylenediamine-(gamma)-folate with 2-(p-isothiocyanobenzyl)-DOTA. Radiolabeling
      was carried out with (67)GaCl(3) according to standard procedures.
      Biodistribution studies of the tracer were performed in mice bearing FR-positive
      KB tumor xenografts. The effects on radiofolate biodistribution with
      coadministered renal uptake-blocking amino acids, diuretic agents, antifolates as
      well as different routes of administration were likewise investigated. Supportive
      imaging studies were performed using a small-animal single photon emission
      computed tomography (SPECT)/CT scanner. RESULTS: (67)Ga-DOTA-Bz-EDA-folate showed
      a high and specific accumulation in tumors (6.30%+/-0.75% ID/g, 1 h pi and
      6.08%+/-0.89% ID/g, 4 h pi). Nonspecific radioactivity uptake in nontargeted
      tissues was negligible, but significant accumulation was found in FR-positive
      kidneys, which resulted in unfavorably low tumor-to-kidney ratios (<0.1).
      Coadministered amino acids or diuretics did not effectively reduce renal
      accumulation; in contrast, predosed pemetrexed did significantly reduce kidney
      uptake (<29% of control values). The SPECT/CT studies confirmed the excellent
      tumor-to-background contrast of (67)Ga-radiofolate and the favorable reduction in
      kidney uptake (with improved imaging quality) resulting from pemetrexed
      administration. CONCLUSION: Conventional methods to reduce kidney uptake of
      radiofolates fail. However, the novel (67)Ga-radiolabeled DOTA-Bz-EDA-folate can
      effectively be used to image FR-positive cancer and potentially inflammatory
      diseases. Due to its rapid blood clearance properties, this tracer is also a
      promising candidate for positron emission tomography imaging if radiolabeled with
      the short-lived [(68)Ga]-gallium radionuclide.

PMID- 21718948
TI  - Effect of cyclosporin A on the uptake of D3-selective PET radiotracers in rat
      brain.
AB  - INTRODUCTION: Four benzamide analogs having a high affinity and selectivity for
      D(3) versus D(2) receptors were radiolabeled with (11)C or (18)F for in vivo
      evaluation. METHODS: Precursors were synthesized, and the four D(3) selective
      benzamide analogs were radiolabeled. The tissue distribution and brain uptake of
      the four compounds were evaluated in control rats and rats pretreated with
      cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux
      transporters that contribute to the blood brain barrier. Micro-positron emission
      tomographic (PET) imaging was carried out for [(11)C]6 in a control and a
      cyclosporin A pretreated rat. RESULTS: All four compounds showed low brain uptake
      in control rats at 5 and 30 min post-injection; despite recently reported rat
      behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following
      administration of cyclosporin A, increased brain uptake was observed with all
      four PET radiotracers at both 5 and 30 min post-intravenous injection. An
      increase in brain uptake following modulation/inhibition of the ABC transporters
      was also observed in the microPET study. CONCLUSIONS: These data suggest that D3
      selective conformationally-flexible benzamide analogs which contain a N-2
      methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other
      adenosine triphosphate (ATP)-binding cassette transporters expressed at the blood
      brain barrier, and that PET radiotracers containing this pharmacophore may
      display low brain uptake in rodents due to the action of these efflux
      transporters.

PMID- 21718949
TI  - Correlative single photon emission computed tomography imaging of [123I]altropane
      binding in the rat model of Parkinson's.
AB  - INTRODUCTION: This study used the dopamine transporter (DAT) probe, [(123)I]
      2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane
      ([(123)I]altropane), to assess the DAT levels in the 6-hydroxydopamine rat model
      of Parkinson's disease. We sought to assess if the right to left
      [(123)I]altropane striatal ratios correlated with dopamine content in the
      striatum and substantia nigra and with behavioural outcomes. METHODS:
      [(123)I]altropane images taken pre- and postlesion were acquired before and after
      the transplantation of neural stem/progenitor cells. The images obtained using
      [(123)I]altropane and single photon emission computed tomography (SPECT) were
      compared with specific behavioural tests and the dopamine content assessed by
      high-performance liquid chromatography. RESULTS: [(123)I]altropane binding
      correlated with the content of dopamine in the striatum; however,
      [(123)I]altropane binding did not correlate with the dopamine content in the
      substantia nigra. There was a significant correlation of altropane ratios with
      the cylinder test and the postural instability test, but not with amphetamine
      rotations. The low coefficient of determination (r(2)) for these correlations
      indicated that [(123)I]altropane SPECT was not a good predictor of behavioural
      outcomes. CONCLUSION: Our data reveal that [(123)I]altropane predicts the
      integrity of the striatal dopamine nerve terminals, but does not predict the
      integrity of the nigrostriatal system. [(123)I]altropane could be a useful marker
      to measure dopamine content in cell replacement therapies; however, it would not
      be able to evaluate outcomes for neuroprotective strategies.

PMID- 21718950
TI  - 99mTc-technetium labeling of antiarthritic peptides to evaluate homing and
      biodistribution at inflamed joints.
AB  - PURPOSE: The aim of this study was to investigate the biodistribution and
      localization of an anti-inflammatory nonapeptide coupled to synovial targeting
      peptide (HAP-1) in rat adjuvant-induced arthritis. PROCEDURE: N(epsilon)
      functionalized histidine derivative was coupled to the N-terminus of core peptide
      (CP) and HAP-1 to allow coupling of (99m)Tc-tricarbonyl linker (Isolink).
      Synovial homing peptide HAP-1 was linked to CP through a peptide bond prior to
      labeling with (99m)Tc. Peptides were purified by high-performance liquid
      chromatography, characterized by mass spectrometry, radiolabeled and injected
      into normal and arthritic rats to determine biodistribution and localization.
      RESULTS: Gamma scintigraphy imaging showed that the biodistribution of all
      (99m)Tc-labeled peptides were higher in the arthritic joints compared with the
      normal nonarthritic joints, at all three time points (10 min, 1 h, 3 h
      postinjection) and attributed to increased blood flow to inflammatory sites. HAP
      1 and CP-HAP-1 showed a greater uptake and localization to arthritic joints
      compared with controls. There was no difference in the physiological
      biodistribution of these agents in the heart, kidneys and the bladder.
      CONCLUSIONS: This study highlights the versatility of using the His derivative
      linker for (99m)Tc tagging of a variety of peptides. It also demonstrates greater
      peptide localization and thereby bioavailability of therapeutic peptides to
      inflamed joints following specific conjugation to homing peptides. The ability to
      localize peptide/drugs to inflamed synovium has important therapeutic
      implications.

PMID- 21718951
TI  - Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human
      sodium iodide symporter gene and herpes simplex virus thymidine kinase gene.
AB  - Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has
      been widely used as a traditional gene therapy modality, and the sodium/iodide
      symporter gene (NIS) has been found to be a novel therapeutic gene. Since the
      therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers
      following NIS or HSV-TK gene transfer need to be enhanced, this study was
      designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma
      via coexpression of NIS gene and HSV-TK gene. METHODS: HepG2 cells were stably
      transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named
      HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain
      reaction, fluorescence imaging and iodide uptake. The therapeutic effects were
      assessed by MTT assay and clonogenic assay. RESULTS: HepG2/NTG cells concentrated
      (125)I(-) up to 76-fold higher than the wild-type cells within 20 min, and the
      efflux happened with a T(1/2eff) of less than 10 min. The iodide uptake in
      HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent
      toxicity to HepG2/NTG cells by either GCV or (131)I was revealed by clonogenic
      assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased
      to 49.7%+/-2.5%, 43.4%+/-2.8% and 8.6%+/-1.2% after exposure to (131)I, GCV and
      combined therapy, respectively. CONCLUSION: We demonstrate that radiochemotherapy
      of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK
      gene leads to stronger killing effect than single treatment, and in vivo studies
      are needed to verify these findings.

PMID- 21718952
TI  - Integrated imaging of cancer metabolism.

PMID- 21718953
TI  - Molecular imaging of malignant tumor metabolism: whole-body image fusion of
      DWI/CT vs. PET/CT.
AB  - PURPOSE: To prospectively investigate the technical feasibility and performance
      of image fusion for whole-body diffusion-weighted imaging (wbDWI) and computed
      tomography (CT) to detect metastases using hybrid positron emission
      tomography/computed tomography (PET/CT) as reference standard. MATERIAL AND
      METHODS: Fifty-two patients (60 +/- 14 years; 18 women) with different malignant
      tumor disease examined by PET/CT for clinical reasons consented to undergo
      additional wbDWI at 1.5 Tesla. WbDWI was performed using a diffusion-weighted
      single-shot echo-planar imaging during free breathing. Images at b = 0 s/mm(2)
      and b = 700 s/mm(2) were acquired and apparent diffusion coefficient (ADC) maps
      were generated. Image fusion of wbDWI and CT (from PET/CT scan) was performed
      yielding for wbDWI/CT fused image data. One radiologist rated the success of
      image fusion and diagnostic image quality. The presence or absence of metastases
      on wbDWI/CT fused images was evaluated together with the separate wbDWI and CT
      images by two different, independent radiologists blinded to results from PET/CT.
      Detection rate and positive predictive values for diagnosing metastases was
      calculated. PET/CT examinations were used as reference standard. RESULTS: PET/CT
      identified 305 malignant lesions in 39 of 52 (75%) patients. WbDWI/CT image
      fusion was technically successful and yielded diagnostic image quality in 73% and
      92% of patients, respectively. Interobserver agreement for the evaluation of
      wbDWI/CT images was kappa = 0.78. WbDWI/CT identified 270 metastases in 43 of 52
      (83%) patients. Overall detection rate and positive predictive value of wbDWI/CT
      was 89% (95% CI, 0.85-0.92) and 94% (95% CI, 0.92-0.97), respectively.
      CONCLUSION: WbDWI/CT image fusion is technically feasible in a clinical setting
      and allows the diagnostic assessment of metastatic tumor disease detecting nine
      of 10 lesions as compared with PET/CT.

PMID- 21718954
TI  - Correlation of immunohistologic and perfusion vascular parameters with MR
      contrast enhancement using image-guided biopsy specimens in gliomas.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to correlate the status
      of magnetic resonance contrast enhancement with immunohistologic vascular
      parameters such as microvascular cellular proliferation (MVCP), microvascular
      density (MVD), vascular endothelial growth factor receptor-2 (VEGFR-2)
      expression, and World Health Organization (WHO) grade obtained from image-guided
      biopsy specimens. We also compared perfusion computed tomography (PCT) parameters
      such as cerebral blood volume (CBV), cerebral blood flow (CBF), and permeability
      surface area-product (PS) with the presence or absence of contrast enhancement.
      MATERIALS AND METHODS: A total of 26 image-guided biopsy specimens in 16 patients
      with treatment naive gliomas were obtained from contrast-enhancing (CE) and
      nonenhancing (NE) regions of the glioma. Contrast enhancement status was
      correlated with MVD, MVCP, VEGFR-2 expression, and WHO grade obtained from the
      biopsy specimen as well as with the PCT parameters. RESULTS: Contrast enhancement
      showed statistically significant correlation with MVCP (P = .003) and PS (P =
      .007) when compared with various immunohistologic and perfusion vascular
      parameters. WHO grade of the biopsy specimen showed statistically significant
      correlation with contrast enhancement (P = .002), MVCP (P < .001), and PS values
      (P = .028). CONCLUSION: Contrast enhancement in gliomas is primarily from a break
      in blood-brain barrier as evidenced by its correlation with PS and MVCP, whereas
      it was not statistically correlated with CBV and MVD even though it showed a
      positive trend. Contrast enhancement also showed significant correlation with WHO
      grade suggesting a biopsy from CE region in a heterogeneous glioma probably will
      still yield the most aggressive part of the glioma is also shown by its
      association with MVCP and PS estimates.

PMID- 21718955
TI  - MR-guided high-intensity focused ultrasound treatment for symptomatic uterine
      leiomyomata: long-term outcomes.
AB  - RATIONALE AND OBJECTIVES: To evaluate the long-term clinical outcomes of magnetic
      resonance--guided high-intensity focused ultrasound (MR-g HIFU) treatments for
      symptomatic uterine leiomyomata. MATERIALS AND METHODS: Patients were recruited
      for a prospective study for MR-g HIFU treatments of symptomatic leiomyomata, with
      up to 3-year follow-up. The study was approved by the institutional review board
      and was Health Insurance Portability and Accountability Act--compliant. Clinical
      assessments were obtained at 3 months, 6 months, and 1, 2, and 3 years after MR-g
      HIFU, as well as uterine fibroid symptom severity scores (SSS) and health-related
      quality of life questionnaires (UFS-QOL). MR imaging was performed at each follow
      up to assess the efficacy of the treatment at 6 months, 1 year, 2 years, and 3
      years. RESULTS: Fifty-one leiomyomata in 40 patients were treated. All patients
      were treated within the US Food and Drug Administration guidelines with
      leiomyomata localized on MR and treated with sonication. The mean baseline volume
      of treated leiomyomata was 336.9 cm(3). The mean improvement scores for
      transformed SSS was 47.8 (P < .001) and for tUFS-QOL was 39.8 (P < .001) at 3
      years. The mean volume decrease in treated leiomyomata was 32.0% (P < .001), and,
      in the uterus, the volume decrease was 27.7% (P < .001) at 3 years. There were no
      long-term complications. CONCLUSIONS: Long-term follow-up data from MR-g HIFU
      treatments show sustained symptomatic relief among enrolled patients. Although
      the results are preliminary, MR-g HIFU for the treatment of uterine leiomyomata
      may result in acceptable long-term outcomes at 3 years.

PMID- 21718956
TI  - Usefulness of computerized method for lung nodule detection in digital chest
      radiographs using temporal subtraction images.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the usefulness of
      a novel computerized method for lung nodule detection on digital chest
      radiographs using temporal subtraction images. MATERIALS AND METHODS: To
      significantly reduce the number of false-positive results while maintaining high
      sensitivity, temporal subtraction images, which can enhance interval changes on
      sequential chest radiographs, were used. Fifty-one cases with lung nodules <3 cm
      and 51 cases without lung nodules were selected for an observer performance test.
      Twelve radiologists participated in this observer performance test. The
      radiologists' performance was evaluated using receiver-operating characteristic
      analysis, on a continuous rating scale. To estimate the numbers of cases affected
      beneficially and those affected detrimentally using this computerized method, the
      computer output was assumed to have an effect on an observer's diagnosis when
      there was a difference in rating score of >=30% between the first and second
      ratings. RESULTS: The average area under the curve for all radiologists increased
      significantly from 0.849 to 0.950 with the computerized method (P < .001). The
      mean number of cases affected beneficially was significantly higher than that of
      cases affected detrimentally (8.92 vs 1.25, P < .001). CONCLUSIONS: The novel
      computerized method using temporal subtraction images would be useful in
      detecting lung nodules on digital chest radiographs.

PMID- 21718957
TI  - The pharmacokinetics of gadodiamide in patients with severe renal insufficiency
      treated conservatively or undergoing hemodialysis or continuous ambulatory
      peritoneal dialysis.

PMID- 21718958
TI  - Every state.

PMID- 21718959
TI  - The effects of urinary trypsin inhibitor on liver function and inflammatory
      factors in patients undergoing hepatectomy: a prospective, randomized, controlled
      clinical study.
AB  - BACKGROUND: The inhibition of inflammation exerts benefits following massive
      hepatectomy in animals but not in the clinic. The aim of this study was to
      investigate the effectiveness and mechanism of ulinastatin on liver function and
      outcomes following hepatectomy. METHODS: One hundred seventy-six patients
      undergoing hepatectomy were randomized into the treatment group (n = 86) and the
      control group (n = 90), receiving ulinastatin 150,000 U twice daily for 3 days
      and saline vehicle, respectively. Liver function, coagulation, thrombokinase,
      lymphocyte subsets CD4 and CD8, C-reactive protein, inducible nitric oxide
      synthase, and cytokines were measured. Clinical outcomes were also evaluated.
      RESULTS: Serum alanine transaminase, aspartate transferase, inducible nitric
      oxide synthase, and tumor necrosis factor-alpha levels were significantly lower
      after ulinastatin treatment, and the response of bilirubin was delayed. The
      benefits of ulinastatin were shown mainly in major hepatectomy earlier after
      surgery. The treatment significantly reduced hospital length of stay and recovery
      related cost. CONCLUSIONS: Ulinastatin protects liver function and improves
      clinical outcomes, possibly via the inhibition of inflammation and oxidation at
      an earlier stage following major hepatectomy.

PMID- 21718960
TI  - Functional alignment, not structural integration, of medical schools and teaching
      hospitals is associated with high performance in academic health centers.
AB  - BACKGROUND: Debates continue regarding optimal structures for governance and
      administration between medical schools and their teaching hospitals. METHODS:
      Structural integration (SI) for 85 academic health centers was characterized as
      high (single leader or fiduciary) or low (multiple leaders or fiduciaries).
      Functional alignment (FA) was estimated from questionnaire responses by teaching
      hospitals' chief executive officers, and an index was calculated quantifying
      organizational collaboration across several functional areas. SI and FA were
      examined for their association with global performance measures in teaching,
      research, clinical care, finance, and efficiency. RESULTS: AHCs with high SI had
      significantly higher FA, though overlap between high-SI and low-SI institutions
      was considerable. SI was not significantly associated with any performance
      measure. In contrast, FA was significantly associated with higher performance in
      teaching, research, and finance but not clinical care and efficiency.
      CONCLUSIONS: FA between medical schools and their primary teaching hospitals more
      strongly predicts academic health centers' performance than does SI. As demands
      for greater collaboration increase under health reform, emphasis should be placed
      on increasing FA rather than SI.

PMID- 21718961
TI  - The formal and informal surgical ethics curriculum: views of resident and staff
      surgeons in Toronto.
AB  - BACKGROUND: Understanding what staff surgeons think surgical trainees should
      learn and the ethical issues that trainees need to manage can strengthen surgical
      ethics education. METHODS: Participants were recruited from the 15 surgical
      specialty and subspecialty programs at the University of Toronto. Semistructured
      interviews and focus groups were conducted with 13 ethics coordinators from the
      surgical staff and 64 resident trainees. Data were analyzed qualitatively using
      modified thematic analysis. RESULTS: All coordinators and trainees felt that
      ethics education was an important component of surgical training. Real cases,
      varying teaching methods, and teachers with applicable clinical experience were
      valued. Trainees identified intraprofessional and interprofessional conflict,
      staff behavior perceived to be unethical, and their own lack of experience as
      challenging issues rarely addressed in the formal ethics curriculum. CONCLUSIONS:
      Ethics education is highly valued by trainees and teachers. Some ethical issues
      important to trainees are underrepresented in the formal curriculum. Staff
      surgeons and senior residents are practicing ethicists and role models whose
      impact on the moral development of residents is profound. Their participation in
      the formal curriculum helps less experienced junior residents realize its value.

PMID- 21718962
TI  - Anomalous aortic origin of a coronary artery: medium-term results after surgical
      repair in 50 patients.
AB  - BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a rare
      congenital heart defect that has been associated with myocardial ischemia and
      sudden death. Controversies exist regarding the diagnosis, treatment, and long
      term recommendations for patients with AAOCA. The purpose of this study is to
      evaluate the medium-term results of surgical repair for AAOCA. METHODS: From
      January 1999 through August 2010, 50 patients underwent surgical repair of AAOCA.
      The median age at surgery was 14 years (range, 5 days to 47 years). Thirty-one
      patients had the right coronary originate from the left sinus of Valsalva, 17 had
      the left coronary originate from the right sinus, and 2 had an eccentric single
      coronary ostium. Twenty six of the 50 patients had symptoms of myocardial
      ischemia preoperatively, and 14 patients had associated congenital heart defects.
      Repair was accomplished by unroofing in 35, reimplantation in 6, and pulmonary
      artery translocation in 9. RESULTS: There was no operative mortality. The median
      time of follow-up has been 5.7 years. Two patients were lost to follow-up, and 1
      patient required heart transplantation 1 year after AAOCA repair. In the
      remaining 47 postoperative patients, all have remained free of cardiac symptoms
      and no one has experienced a sudden death event. CONCLUSIONS: The surgical
      treatment of AAOCA is safe and appears to be highly effective in eliminating
      ischemic symptoms. These medium-term results are encouraging and suggest that
      many patients may be able to resume normal activities.

PMID- 21718963
TI  - Office task effects on comfort and body dynamics in five dynamic office chairs.
AB  - In the present study, we investigated the effect of office tasks on posture and
      movements in field settings, and the comfort rating for chair characteristics and
      correlation with type of task. The tasks studied were: computer work,
      telephoning, desk work and conversation. Postures, movements, chair part
      inclinations and comfort rating data were collected from 12 subjects. Computer
      work showed the lowest physical activity, together with upright trunk and head
      position and low backrest inclination. Conversation shows the highest activity of
      head legs and low back together with the highest cervical spine extension. In
      contrast, desk work provoked the most cervical spine flexion and showed the
      second lowest activity. The telephoning tasks showed medium activity and the
      highest kyphosis. Conversation showed the highest backrest inclination. Positive
      comfort relations were found for computer work and a "swing system" chair, for
      telephoning and an active longitudinal seat rotation, and for desk work and a
      chair with a three-dimensionally moveable seat.

PMID- 21718964
TI  - Changes in sleep and wake in response to different sleeping surfaces: a pilot
      study.
AB  - Six married couples (12 adults, mean age 34.8 years) were randomized as couples
      in a cross-over design to sleep on a queen-size conventional mattress for 2 weeks
      and a specially-designed pressure-relief mattress for 2 weeks. The pressure
      relief mattress was designed to reduce the number of contact points exceeding 30
      mm Hg. Actigraphic measurements of sleep and self-reports of sleep and daytime
      symptoms were collected at baseline for 2 weeks on each couple's home mattress
      and box springs at home, followed by 2 weeks of data collection on each
      randomized mattress for a total of 6 weeks of data collection. Pressure maps were
      created for each participant on each sleeping surface. There were no significant
      differences between the randomized sleeping surfaces for any measure of
      actigraphic sleep or self-reported sleep and daytime symptoms. However, poor
      pressure relief performance of the home mattress was associated with better
      actigraphic sleep on the randomized pressure-relief mattress. We conclude that
      while pressure-relief mattresses may not be universally preferred, baseline
      characteristics of the sleeper and/or their mattress may explain performance and
      sleeper preferences on future mattress selection.

PMID- 21718965
TI  - Expression of functional Stim1-mKO1 in rat submandibular acinar cells by
      retrograde ductal injection of an adenoviral vector.
AB  - OBJECTIVE: Adenoviruses are used for gene transfer to salivary glands cells in
      vivo. We constructed an adenovirus vector that expressed a fusion protein of
      human Stim1 and the fluorescent protein mKO1 (Ad-Stim1-mKO1), and used it to
      investigate the molecular dynamics and functions of exogenously expressed
      proteins in living salivary acinar cells. DESIGN: Ad-Stim1-mKO1 was transferred
      to rat submandibular glands by retrograde ductal injection. Expression and
      distribution of Stim1-mKO1 were examined by confocal microscopy. In addition, the
      effects of Stim1-mKO1 on store-operated Ca(2+) entries were examined in fura-2
      loaded cells. RESULTS: The expression of Stim1-mKO1 was detected in approximately
      40% of rat submandibular acini, whereas the expression in HSY-EA1 cells was ~80%.
      Confocal microscopy revealed Stim1-mKO1 fluorescence along the endoplasmic
      reticulum-like network in the cytoplasm of both HSY-EA1 and dispersed acinar
      cells. The depletion of intracellular Ca(2+) stores with thapsigargin (ThG), a
      sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitor, led to the
      translocation of Stim1-mKO1 to the peripheral region in these cells. In addition,
      expression of Stim1-mKO1 enhanced store-operated Ca(2+) entry in these cells.
      CONCLUSIONS: We succeeded in expressing Stim1-mKO1 fluorescent protein in the
      salivary glands of live animals by retrograde ductal injection of an adenoviral
      vector. This method allowed us to investigate the functions and molecular
      dynamics of these expressed molecules in living salivary acinar cells.

PMID- 21718966
TI  - Comparison of virtual reality versus physical reality on movement characteristics
      of persons with Parkinson's disease: effects of moving targets.
AB  - OBJECTIVE: To compare the performance of reaching for stationary and moving
      targets in virtual reality (VR) and physical reality in persons with Parkinson's
      disease (PD). DESIGN: A repeated-measures design in which all participants
      reached in physical reality and VR under 5 conditions: 1 stationary ball
      condition and 4 conditions with the ball moving at different speeds. SETTING:
      University research laboratory. PARTICIPANTS: Persons with idiopathic PD (n=29)
      and age-matched controls (n=25). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Success rates and kinematics of arm movement (movement time, amplitude
      of peak velocity, and percentage of movement time for acceleration phase).
      RESULTS: In both VR and physical reality, the PD group had longer movement time
      (P<.001) and lower peak velocity (P<.001) than the controls when reaching for
      stationary balls. When moving targets were provided, the PD group improved more
      than the controls did in movement time (P<.001) and peak velocity (P<.001), and
      reached a performance level similar to that of the controls. Except for the
      fastest moving ball condition (0.5-s target viewing time), which elicited worse
      performance in VR than in physical reality, most cueing conditions in VR elicited
      performance generally similar to those in physical reality. CONCLUSIONS: Although
      slower than the controls when reaching for stationary balls, persons with PD
      increased movement speed in response to fast moving balls in both VR and physical
      reality. This suggests that with an appropriate choice of cueing speed, VR is a
      promising tool for providing visual motion stimuli to improve movement speed in
      persons with PD. More research on the long-term effect of this type of VR
      training program is needed.

PMID- 21718967
TI  - Emotion dysregulation and adolescent psychopathology: a prospective study.
AB  - BACKGROUND: Emotion regulation deficits have been consistently linked to
      psychopathology in cross-sectional studies. However, the direction of the
      relationship between emotion regulation and psychopathology is unclear. This
      study examined the longitudinal and reciprocal relationships between emotion
      regulation deficits and psychopathology in adolescents. METHODS: Emotion
      dysregulation and symptomatology (depression, anxiety, aggressive behavior, and
      eating pathology) were assessed in a large, diverse sample of adolescents
      (N=1065) at two time points separated by seven months. Structural equation
      modeling was used to examine the longitudinal and reciprocal relationships
      between emotion dysregulation and symptoms of psychopathology. RESULTS: The three
      distinct emotion processes examined here (emotional understanding, dysregulated
      expression of sadness and anger, and ruminative responses to distress) formed a
      unitary latent emotion dysregulation factor. Emotion dysregulation predicted
      increases in anxiety symptoms, aggressive behavior, and eating pathology after
      controlling for baseline symptoms but did not predict depressive symptoms. In
      contrast, none of the four types of psychopathology predicted increases in
      emotion dysregulation after controlling for baseline emotion dysregulation.
      CONCLUSIONS: Emotion dysregulation appears to be an important transdiagnostic
      factor that increases risk for a wide range of psychopathology outcomes in
      adolescence. These results suggest targets for preventive interventions during
      this developmental period of risk.

PMID- 21718968
TI  - Brain type 1 cannabinoid receptor availability in patients with anorexia and
      bulimia nervosa.
AB  - BACKGROUND: The endocannabinoid system is a possible target in the treatment of
      eating disorders. We used positron emission tomography to investigate the type 1
      cannabinoid receptor (CB1R) in bulimic and anorectic patients. METHODS: We
      investigated 16 female bulimia nervosa patients (BN) (age = 23.8 +/- 7.1 years)
      and 14 female anorexia nervosa patients (AN) (age = 20.5 +/- 3.6 years) using the
      selective CB1R ligand [(18)F]MK-9470. The control group consisted of 19 age
      matched women (age = 25.2 +/- 8.5 years). Statistical parametric mapping
      (p(family-wise error) < .05) and volume-of-interest analyses of CB1R availability
      were performed. RESULTS: Global CB1R availability was significantly increased in
      cortical and subcortical brain areas in AN patients compared with healthy control
      subjects (+24.5%, p = .0003). Regionally, CB1R availability was increased in the
      insula in both AN and BN patients (p = .01 and p = .0004) and the inferior
      frontal and temporal cortex in AN patients only (p = .02). CONCLUSIONS: Global
      CB1R upregulation in AN patients is a possible long-term compensatory mechanism
      to an underactive endocannabinoid system in anorectic conditions. There is a
      similarity in CB1R dysregulation both in AN and BN in the insular cortex, which
      is involved in the integration of interoceptive information, gustatory
      information, reward, and emotion processing.

PMID- 21718969
TI  - Altered temporal difference learning in bulimia nervosa.
AB  - BACKGROUND: The neurobiology of bulimia nervosa (BN) is poorly understood. Recent
      animal literature suggests that binge eating is associated with altered brain
      dopamine (DA) reward function. In this study, we wanted to investigate DA-related
      brain reward learning in BN. METHODS: Ill BN (n = 20, age: mean = 25.2, SD = 5.3
      years) and healthy control women (CW) (n = 23, age: mean = 27.2, SD = 6.4 years)
      underwent functional magnetic resonance brain imaging together with application
      of a DA-related reward learning paradigm, the temporal difference (TD) model.
      That task involves association learning between conditioned visual and
      unconditioned taste stimuli, as well as unexpected violation of those learned
      associations. Study participants also completed the Sensitivity to Reward and
      Punishment Questionnaire. RESULTS: Bulimia nervosa individuals showed reduced
      brain response compared with CW for unexpected receipt and omission of taste
      stimuli, as well as reduced brain regression response to the TD computer model
      generated reward values, in insula, ventral putamen, amygdala, and orbitofrontal
      cortex. Those results were qualitatively similar in BN individuals who were
      nondepressed and unmedicated. Binge/purge frequency in BN inversely predicted
      reduced TD model response. Bulimia nervosa individuals showed significantly
      higher Sensitivity to Reward and Punishment compared with CW. CONCLUSIONS: This
      is the first study that relates reduced brain DA responses in BN to the altered
      learning of associations between arbitrary visual stimuli and taste rewards. This
      attenuated response is related to frequency of binge/purge episodes in BN. The
      brain DA neurotransmitter system could be an important treatment target for BN.

PMID- 21718970
TI  - Hydrogen supplemented air inhalation reduces changes of prooxidant enzyme and gap
      junction protein levels after transient global cerebral ischemia in the rat
      hippocampus.
AB  - Transient global cerebral ischemia (TGCI) occurs during acute severe hypotension
      depriving the brain of oxygen and glucose for a short period of time. During
      reperfusion, several mechanisms can induce secondary neuronal damage, including
      the increased production of reactive oxygen species (ROS). Hydrogen gas-enriched
      air inhalation is a neuroprotective approach with proven antioxidant potential,
      which has not yet been examined in TGCI. Accordingly, we set out to describe the
      effect of inhalation of 2.1% hydrogen supplemented room air (H(2)-RA) in
      comparison with a well studied neuroprotective agent, rosiglitazone (RSG) in a
      TGCI rat model. Male Wistar rats were exposed to TGCI (n=26) or sham operation
      (n=26), while a third group served as intact control (naive, n=5). The operated
      groups were further divided into non-treated, H(2)-RA, RSG (6 mg/kg i.v.) and
      vehicle treated animals. Tissue samples from the hippocampus and frontal cortex
      were taken 3 days following surgery. Western blot analysis was applied to
      determine the expressions of cyclooxygenase-2 (COX-2), neuronal and endothelial
      nitric oxide synthase (nNOS and eNOS, respectively), manganese superoxide
      dismutase (MnSOD) and glial connexin proteins: connexin 30 and connexin 43. The
      expressions of COX-2, and connexin proteins were upregulated, while nNOS was
      downregulated 3 days after TGCI. Both RSG and H(2)-RA prevented the changes of
      enzyme and connexin levels. Considering the lack of harmful side effects,
      inhalation of H(2)-RA can be a promising approach to reduce neuronal damage after
      TGCI.

PMID- 21718972
TI  - Effect of adhesive on the morphology and mechanical properties of electrospun
      fibrous mat of cellulose acetate.
AB  - Ultrafine fibers of cellulose acetate/poly(butyl acrylate) (CA/PBA) composite in
      which PBA acted as an adhesive and CA acted as a matrix, were successfully
      prepared as fibrous mat via electrospinning. The morphology observation from the
      electrospun CA/PBA composite fibers, after treatment with heat hardener, revealed
      that the fibers were cylindrical and had point-bonded structures. SEM, FT-IR
      spectra, Raman spectra, TGA analysis, and mechanical properties measurement were
      used to study the different properties of hybrid mats. The tensile strength of
      blend fibrous electrospun mats was found to be effectively increased. This
      resultant enhancement of the mechanical properties of polymer fibrous mats,
      caused by generating the point-bonded structures (due to adhesive), could
      increase the number of potential applications of mechanically weak electrospun CA
      fibers.

PMID- 21718971
TI  - Bax inhibitor 1, a modulator of calcium homeostasis, confers affective
      resilience.
AB  - The endoplasmic reticulum (ER) is a critical site for intracellular calcium
      storage as well as protein synthesis, folding, and trafficking. Disruption of
      these processes is gaining support for contributing to heritable vulnerability of
      certain diseases. Here, we investigated Bax inhibitor 1 (BI-1), an anti-apoptotic
      protein that primarily resides in the ER and associates with B-cell lymphoma 2
      (Bcl-2) and Bcl-XL, as an affective resiliency factor through its modulation of
      calcium homeostasis. We found that transgenic (TG) mice with BI-1 reinforced
      expression, via the neuronal specific enolase promoter, showed protection against
      the learned helplessness (LH) paradigm, an animal model to test stress coping. TG
      mice were also protected against anhedonia following both serotonin and
      catecholamine depletion as measured in two different models, the female urine
      sniffing test and the saccharine preference test. In addition, we used primary
      mouse cortical cultures to explore the ability of BI-1 to influence calcium
      homeostasis under basal conditions and also following challenge with thapsigargin
      (THPS), an inhibitor of sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) that
      disrupts calcium homeostasis. TG neurons showed decreased basal cytosolic calcium
      levels and decreased Ca(2+) cytosolic accumulation following challenge with THPS
      as compared to WT neuronal cultures. Together, these data suggest that BI-1,
      through its actions on calcium homeostasis, may confer affective resiliency in
      multiple animal models of depression and anhedonia.

PMID- 21718973
TI  - Novel teichulosonic acid from cell walls of some representatives of the genus
      Kribbella.
AB  - Cell walls of each of five bacterial strains belonging to the genus Kribbella
      (family Nocardioidaceae, order Actinomycetales) contain a neutral polysaccharide
      (mannan) and teichulosonic acid of novel structure in different proportions. The
      novel teichulosonic acid found in strains VKM Ac-2500, VKM As-2568, VKM As-2572,
      and VKM As-2575 is a heteropolymer with an irregular structure where fragments I
      (predominant) alternate with fragments II (minor): The teichulosonic acid from
      Kribbella sp. VKM Ac-2527 has in general a structure similar to that above with
      the exception that the Pse residue is randomly glycosylated at O-4 with beta-l
      Rhap (along with alpha-d-Galp3OMe or alpha-d-Galp2,3OMe). The strain VKM Ac-2572
      contained additionally teichuronic acid with the disaccharide repeating unit
      consisted of aminomannuronic acid and 2,3-diacetamido-2,3-dideoxy-alpha
      glucopyranose. The mannan, a polysaccharide common to all of the strains, is
      built of (1->6)-linked alpha-d-mannopyranose substituted with alpha-d
      mannopyranose at O-2. The structures of all the glycopolymers were established by
      a combination of chemical and NMR spectroscopic methods.

PMID- 21718974
TI  - Synthesis and characterization of a novel polyamidoamine-cyclodextrin crosslinked
      copolymer.
AB  - A novel insoluble crosslinked copolymer containing beta-cyclodextrin (beta-CD)
      structural units has been synthesized with polyamidoamine (PAMAM, generation 2)
      as comonomer. The polymer was characterized using Fourier-transform infrared
      spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), elemental analysis,
      scanning electron microscopy (SEM), pores and surface area analysis, X-ray
      diffraction analysis (XRD), and thermal analysis (thermogravimetric and
      differential scanning calorimetric measurement, TG/DSC). The results reveal that
      PAMAM-CD copolymer has been synthesized successfully and two beta-CD molecules
      were cross-linked by one PAMAM (G2.0) molecule (on average). The copolymer has a
      reef-like surface with many irregular nanocavities, and its thermal stability is
      > 180 degrees C in an argon atmosphere. The synthesis strategy presented in this
      work provides an innovative route for the synthesis of a PAMAM-CD-based
      copolymer. In preliminary sorption experiments, the PAMAM-CD copolymer exhibits
      high sorption capacities and high removal efficiencies toward both the heavy
      metal ions (Cu(2+) and Pb(2+)) and organic compounds (2,4-dichlorophenol, 2,4,6
      trichlorophenol, and ponceau 4R (C.I. 16255)). The polymer may provide many
      possibilities for applications in biomedical sensing, flocculation, sorption, and
      therapeutics.

PMID- 21718975
TI  - [Combined endoscopic ballon dilation and intralesional corticosteroid treatment
      of colorectal anastomotic stenosis refractary to dilatation alone].

PMID- 21718976
TI  - How reassuring is a normal breast ultrasound in assessment of a screen-detected
      mammographic abnormality? A review of interval cancers after assessment that
      included ultrasound evaluation.
AB  - AIM: To review factors resulting in a false-negative outcome or delayed cancer
      diagnosis in women recalled for further evaluation, including ultrasound, after
      an abnormal screening mammogram. MATERIALS AND METHODS: Of 646,692 screening
      mammograms performed between 1 January 1995 and 31 December 2004, 34,533 women
      were recalled for further assessment. Nine hundred and sixty-four interval
      cancers were reported in this period. Forty-six of these women had been recalled
      for further assessment, which specifically included ultrasound evaluation in the
      preceding 24 months, and therefore, met the inclusion criteria for this study.
      Screening mammograms, further mammographic views, ultrasound scans, clinical
      findings, and histopathology results were retrospectively reviewed by two
      consultant breast radiologists. RESULTS: The interval cancer developed in the
      contralateral breast (n=9), ipsilateral breast, but different site (n=6), and
      ipsilateral breast at the same site (n=31) as the abnormality for which they had
      recently been recalled. In the latter group, 10 were retrospectively classified
      as a false-negative outcome, nine had a delay in obtaining a biopsy, and 12 had a
      delay due to a non-diagnostic initial biopsy. Various factors relating to these
      outcomes are discussed. CONCLUSION: Out of 34,533 women who attended for an
      assessment visit and the 46 women who subsequently developed an interval breast
      cancer, 15 were true interval cancers, 10 had a false-negative assessment
      outcome, and 21 had a delay to cancer diagnosis on the basis of a number of
      factors. When there is discrepancy between the imaging and histopathology
      results, a repeat biopsy rather than early follow-up would have avoided a delay
      in some cases. A normal ultrasound examination should not deter the radiologist
      from proceeding to stereotactic biopsy, if the index mammographic lesion is
      suspicious of malignancy.

PMID- 21718977
TI  - Differentiation between right tubo-ovarian abscess and appendicitis using CT--a
      diagnostic challenge.
AB  - AIM: To determine CT features that can potentially differentiate right tubo
      ovarian abscess (TOA) from acute appendicitis (AA; including abscess formation).
      MATERIALS AND METHODS: The abdominal computed tomography (CT) images of 48
      patients with right-sided TOA (average age 39.3 +/- 9.8 years) and 80 patients
      (average age 53.5 +/- 19.9 years) with AA (24 with peri-appendicular abscess)
      were retrospectively evaluated. Two experienced radiologists evaluated 12 CT
      signs (including enlarged, thickened wall ovary, appendix diameter and wall
      thickness, peri-appendicular fluid collection, adjacent bowel wall thickening,
      fat stranding, free fluid, and extraluminal gas) in consensus to categorize the
      studies as either TOA or AA. The diagnosis and the frequency of each of the signs
      were correlated with the surgical and clinical outcome. RESULTS: Reviewers
      classified 92% cases correctly (TOA=85%, AA=96.3%), 3% incorrectly (TOA=6.3%,
      AA=1.3%); 5% were equivocal (TOA=8.3%, AA=2.5%). In the peri-appendicular abscess
      group reviewers were correct in 100%. Frequent findings in the TOA group were an
      abnormal ovary (87.5%), peri-ovarian fat stranding (58.3%), and recto-sigmoid
      wall thickening (37.5%). An abnormal appendix was observed in 2% of TOA patients.
      Frequent findings in the AA group were a thickened wall (32.5%) and distended
      (80%) appendix. Recto-sigmoid wall thickening was less frequent in AA (12.5%).
      The appendix was not identified in 45.8% of the TOA patients compared to 15% AA.
      CONCLUSIONS: In the presence of a right lower quadrant inflammatory mass, peri
      ovarian fat stranding, thickened recto-sigmoid wall, and a normal appearing
      caecum, in young patients favour the diagnosis of TOA. An unidentified appendix
      does not contribute to the differentiation between TOA and peri-appendicular
      abscess.

PMID- 21718978
TI  - Simulated annealing implementation with shorter Markov chain length to reduce
      computational burden and its application to the analysis of pulmonary airway
      architecture.
AB  - A new way to implement the Simulated Annealing (SA) algorithm was developed and
      tested that improves computation performance by using shorter Markov chain length
      (inner iterations) and repeating the entire SA process until the final function
      value meets the solution criterion. The new approach coupled with the adaptive
      neighborhood method was tested on the Rosenbrock function in 4 and 13 dimensions.
      This implementation significantly improved the computation speed without
      degrading solution quality. The proposed implementation was used to characterize
      pulmonary architecture from micro CT image data demonstrating the algorithm's
      effectiveness especially for problems with high computational demand and when the
      solution quality requirement can be pre-specified. Using this implementation,
      detailed statistics of the morphometry of conducting airways from 12 male Sprague
      Dawley rats were obtained for each lobe.

PMID- 21718979
TI  - Fronto-striatal circuitry and inhibitory control in autism: findings from
      diffusion tensor imaging tractography.
AB  - INTRODUCTION: Repetitive behaviour and inhibitory control deficits are core
      features of autism; and it has been suggested that they result from differences
      in the anatomy of striatum; and/or the 'connectivity' of subcortical regions to
      frontal cortex. There are few studies, however, that have measured the micro
      structural organisation of white matter tracts connecting striatum and frontal
      cortex. AIMS: To investigate differences in bulk volume of striatum and micro
      structural organisation of fronto-striatal white matter in people with autism;
      and their association with repetitive behaviour and inhibitory control. METHODS:
      We compared the bulk volume of striatum (caudate nucleus, putamen and nucleus
      accumbens) and white matter organisation of fronto-striatal tracts using
      (respectively) structural magnetic resonance imaging (sMRI) and tract specific
      diffusion tensor imaging (DTI) measures in 21 adults with autism and 22 controls.
      We also assessed performance on a cognitive inhibition (go/nogo) task. RESULTS:
      Bulk volume of striatal structures did not differ between groups. However, adults
      with autism had a significantly smaller total brain white matter volume, lower
      fractional anisotropy of white matter tracts connecting putamen to frontal
      cortical areas, higher mean diffusivity of white matter tracts connecting
      accumbens to frontal cortex and worse performance on the go/nogo task. Also,
      performance on the go/nogo task was significantly related to anatomical variation
      when both groups were combined; but not within the autism group alone.
      CONCLUSIONS: These data suggest that autism may be associated with differences in
      the anatomy of fronto-striatal white matter tracts.

PMID- 21718980
TI  - Can syntax appear in a mirror (system)?
AB  - Converging evidence indicates that the processing of some aspects related to the
      phonetic and the semantic components of language is tightly associated with both
      the perceptual and the motor neural systems. It has been suggested that mirror
      neurons contribute to language understanding by virtue of a neurophysiological
      response matching perceptual linguistic information onto corresponding motor
      plans. This proposal has sometimes been extended to advocate that the language
      competence as a whole, including syntax, may be ascribed to this kind of
      perceptuo-motor mappings. This position paper examines what kinds of empirical
      and theoretical challenges such general mirror neuron language accounts need to
      face in order to proof their validity--challenges that we think have not been
      adequately addressed yet. We highlight that the most important limitation is
      constituted by the fact that some core defining properties of human language, at
      the phonetic, semantic, and especially at the syntactic level, are not
      transparent to the bodily senses and thus they cannot be the direct source of
      mirror neuron perceptuo-motor matching.

PMID- 21718983
TI  - Clinical application of oocyte vitrification: a systematic review and meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: To perform a systematic review of the literature to identify
      randomized controlled trials assessing the efficacy of oocyte vitrification in
      terms of oocyte survival, fertilization, embryo development, and pregnancy rates.
      DESIGN: Systematic review and meta-analysis of randomized controlled trials.
      SETTING: Private university-affiliated IVF center, university-based hospital.
      PATIENT(S): Patients recruited in randomized controlled trials considering oocyte
      vitrification as one of the experimental arms and slow freezing or fresh oocytes
      control as the other. INTERVENTION(S): Vitrification of human oocytes vs. slow
      freezing or fresh oocytes. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate;
      secondary outcomes were clinical pregnancy rate, implantation rate, embryo
      development, fertilization rate, and oocyte survival. RESULT(S): Five eligible
      studies were finally included. They involved 4,282 vitrified oocytes, 3,524 fresh
      oocytes, and 361 slow-frozen oocytes between 2005 and 2009. The rates of ongoing
      pregnancy, top-quality embryo, embryo cleavage, and fertilization did not differ
      between the vitrification and the fresh oocyte groups. The oocyte survival rate
      was higher in vitrified vs. slow-frozen oocytes (odds ratio [OR] 2.46, 95%
      confidence interval [CI] 1.82-3.32), although heterogeneity between studies was
      observed. The fertilization rate was higher in vitrified vs. slow-frozen oocytes
      (OR 1.50, 95% CI 1.07-2.11). Vitrification also resulted in a higher rate top
      quality embryo (22.4% vs. 8.0%, OR 3.32, 95% CI 1.37-8.02) and embryo cleavage
      rate (day 2: 64.6% vs. 47.7%, OR 2.00, 95% CI 1.33-3.00; day 3: 53.0% vs. 33.3%,
      OR 2.25, 95% CI 1.32-3.85) as compared with slow freezing. CONCLUSION(S):
      Vitrification is an efficient method to preserve oocytes, although more large
      controlled clinical trials are needed to strengthen this conclusion.

PMID- 21718982
TI  - Impact of endometriosis on quality of life and work productivity: a multicenter
      study across ten countries.
AB  - OBJECTIVE: To assess the impact of endometriosis on health-related quality of
      life (HRQoL) and work productivity. DESIGN: Multicenter cross-sectional study
      with prospective recruitment. SETTING: Sixteen clinical centers in ten countries.
      PATIENT(S): A total of 1,418 premenopausal women, aged 18-45 years, without a
      previous surgical diagnosis of endometriosis, having laparoscopy to investigate
      symptoms or to be sterilized. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Diagnostic delay, HRQoL, and work productivity. RESULT(S): There was a delay of
      6.7 years, principally in primary care, between onset of symptoms and a surgical
      diagnosis of endometriosis, which was longer in centers where women received
      predominantly state-funded health care (8.3 vs. 5.5 years). Delay was positively
      associated with the number of pelvic symptoms (chronic pelvic pain,
      dysmenorrhoea, dyspareunia, and heavy periods) and a higher body mass index.
      Physical HRQoL was significantly reduced in affected women compared with those
      with similar symptoms and no endometriosis. Each affected woman lost on average
      10.8 hours (SD 12.2) of work weekly, mainly owing to reduced effectiveness while
      working. Loss of work productivity translated into significant costs per
      woman/week, from US$4 in Nigeria to US$456 in Italy. CONCLUSION(S): Endometriosis
      impairs HRQoL and work productivity across countries and ethnicities, yet women
      continue to experience diagnostic delays in primary care. A higher index of
      suspicion is needed to expedite specialist assessment of symptomatic women.
      Future research should seek to clarify pain mechanisms in relation to
      endometriosis severity.

PMID- 21718984
TI  - Hysteroscopic morcellator system can be used for removal of a uterine septum.
AB  - OBJECTIVE: To evaluate whether the hysteroscopic morcellator (HM) can be used as
      an alternative for uterine septum removal. DESIGN: Case report. SETTING:
      Outpatient clinic of a university-affiliated teaching hospital (Catharina
      Hospital, Eindhoven, the Netherlands). PATIENT(S): A 34-year-old Asian woman with
      recurrent miscarriages and a large uterine septum and bicornuate uterus.
      INTERVENTION(S): Septum removal using the HM. MAIN OUTCOME MEASURE(S): Successful
      removal of a uterine septum. RESULT(S): Considering obstetric complications,
      septum removal was carried out. Currently, septum transection using the
      resectoscope is the gold standard. Instead of transection we achieved nearly
      complete removal of a septum, using the HM. CONCLUSION(S): The HM is a safe,
      effective, and easily manageable alternative for uterine septum removal compared
      with classic resectoscopy.

PMID- 21718985
TI  - Birth of a healthy boy using fresh testicular sperm in a patient with Klinefelter
      syndrome combined with Kartagener syndrome.
AB  - OBJECTIVE: To report a case of Klinefelter syndrome combined with Kartagener
      syndrome. DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): A 35-year
      old man with Klinefelter syndrome combined with Kartagener syndrome causing
      primary infertility. INTERVENTION(S): Testicular sperm extraction (TESE) and
      intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm recovery,
      fertilization, and live birth. RESULT(S): Ovulation induction of the female
      partner, recovery of spermatozoa by TESE from the male partner and ICSI of 9
      metaphase II oocytes resulted in two fertilized oocytes. The delivery of a
      healthy boy with normal anatomy and 46,XY karyotype was achieved after the
      transfer of only one 4-cell grade 1 embryo. CONCLUSION(S): To our knowledge, this
      case with nonmosaic Klinefelter syndrome combined with Kartagener's syndrome is
      unique and demonstrates the revolutionary aspects of assisted reproductive
      technologies (ART) concerning male factor infertility.

PMID- 21718986
TI  - Functional and anatomic results after creation of a neovagina according to
      Wharton-Sheares-George in patients with Mayer-Rokitansky-Kuster-Hauser syndrome
      long-term follow-up.
AB  - OBJECTIVE: To evaluate the long-term outcomes and degree of satisfaction after
      neovaginoplasty according to Wharton-Sheares-George in women with Mayer
      Rokitansky-Kuster-Hauser syndrome. DESIGN: Open, monocentric follow-up study.
      SETTING: University hospital and referral center for pediatric and adolescent
      gynecology. PATIENT(S): Ten patients with Mayer-Rokitansky-Kuster-Hauser syndrome
      with neovaginas created according to Wharton-Sheares-George 3 to 77 months ago.
      INTERVENTION(S): Gynecologic follow-up examination, including vaginal swab,
      bacterial culture, Papanicolaou smear, hybrid capture test for human
      papillomavirus typing, biopsy, pelvic ultrasound, and 2 questionnaires concerning
      global quality of life and degree of sexual satisfaction. MAIN OUTCOME
      MEASURE(S): Satisfaction with sexual function, quality of life, length and width
      of neovagina, structure of vaginal epithelium, and type of bacterial
      colonization. RESULT(S): Functional long-term follow-up results showed a high
      subjective degree of general well-being and sexual satisfaction in affected
      women. A satisfactory neovaginal length (mean, 8.3 +/- 1.06 cm; range, 7-10 cm)
      and width (mean, 3.3 +/- 0.5 cm; range, 2.5-4 cm) was obtained. As revealed by
      smears and biopsy, the neovagina resembled a natural vagina with regard to type
      of bacterial colonization and structure of epithelium. CONCLUSION(S): The goal of
      any method of creating a neovagina is to provide the patient the possibility to
      have satisfactory sexual intercourse and to enhance well-being and quality of
      life. These aims can be achieved by creating a neovagina according to Wharton
      Sheares-George.

PMID- 21718987
TI  - Apoptosis-inhibitor Aven is downregulated in defective spermatogenesis and a
      novel estrogen target gene in mammalian testis.
AB  - OBJECTIVE: To study the expression and localization of Aven in rat and human
      testis from azoospermic patients with different etiologies and its regulation by
      estrogens. DESIGN: Experimental study. SETTING: University research center and
      private IVF clinic. PATIENT(S): Six men with obstructive azoospermia, five with
      hypospermatogenesis, and six with Sertoli cell-only syndrome; male Wistar rats.
      INTERVENTION(S): Testicular biopsies and rat seminiferous tubules (SeT) cultured
      in the presence or absence of 17beta-estradiol (E(2)). MAIN OUTCOME MEASURE(S):
      Testicular cell localization of Aven protein was analyzed by
      immunohistochemistry. Expression levels of Aven in testicular biopsies and
      cultured SeT, in the presence or absence of 17beta-estradiol, were determined by
      quantitative reverse transcription-polymerase chain reaction and Western blot.
      RESULT(S): Aven is expressed in Sertoli cells, spermatocytes, and spermatogonia
      of both rat and human testis. Aven is underexpressed in the testis of men with
      nonobstructive azoospermia, and its expression levels correlate with severity of
      spermatogenic status. Aven expression is regulated by E(2) in rat SeT cultured ex
      vivo. CONCLUSION(S): The results suggest that deregulation of the expression of
      the apoptosis inhibitor Aven may be related to male factor infertility. Moreover,
      Aven is an estrogen target gene and may be involved in the mechanism of
      testicular apoptosis control by estrogens.

PMID- 21718988
TI  - Presurgical management of dysmenorrhea and endometriosis in a patient with Mayer
      Rokitansky-Kuster-Hauser syndrome.
AB  - OBJECTIVE: To report a patient with Mayer-Rokitansky-Kuster-Hauser syndrome with
      functional endometrium treated with preoperative continuous combined low-dose
      monophasic oral contraceptives. DESIGN: Case report. SETTING: University
      hospital. PATIENT(S): A 12-year-old nulligravid adolescent girl. INTERVENTION(S):
      Preoperative continuous combined low-dose monophasic oral contraceptives for 7
      months, and laparoscopic resection of the rudimentary uterus and uterine horns
      with unilateral salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Relief of pain
      after hormonal treatment and the operative procedure. RESULT(S): Successful
      preoperative treatment of endometriosis and pain before definitive diagnosis and
      removal of mullerian remnants in a patient with Mayer-Rokitansky-Kuster-Hauser
      syndrome. CONCLUSION(S): Patients with obstructive mullerian malformations with
      functional endometrium can be preoperatively managed with continuous combined low
      dose monophasic oral contraceptives to control pain and treat endometriosis. This
      may permit a delay in surgical intervention to facilitate other investigations
      and to allow thorough counselling of the patient and her family about the
      implications of the diagnosis.

PMID- 21718989
TI  - Cryopreservation: a cold look at technology for fertility preservation.
AB  - OBJECTIVE: To outline the history of cryopreservation technology and its
      contributions to reproductive medicine, including fertility preservation. DESIGN:
      A search of the relevant literature using Medline and other online tools.
      SETTING: Research and laboratory protocol development. RESULT(S): The biology of
      preserving cells at low temperatures is complex and still being unraveled.
      Principles were first established more than half a century ago, with progress
      being driven empirically and often by trial and error. The protocols vary widely,
      and practice is still heavily dependent on operator skill, accounting for wide
      differences in the success rates between centers. No single protocol fits all
      specimen types, and differential vulnerability to cryoinjury remains a major
      obstacle. Nevertheless, semen cryopreservation has long been established, embryo
      banking is now highly effective, and vitrification appears to overcome problems
      with oocytes. Protocols in the future, although specific to the cell type and
      tissue, are likely to evolve toward generally acknowledged standards. But
      heterogeneity between patients and even within samples implies that each cell may
      have its own peculiar optimum for minimizing cryoinjury; because protocols are
      therefore compromises, "perfect" preservation may be unattainable. CONCLUSION(S):
      Cryopreservation has become a mainstay in the assisted reproduction laboratory
      and underpins fertility preservation for patients with cancer and other
      conditions. The practice is currently evolving from slow freezing methods toward
      more vitrification, and future technology is likely to reduce dependence on
      operator skill, which should raise success rates to higher, more uniform levels.

PMID- 21718990
TI  - Birth outcomes of intended pregnancies among women who used assisted reproductive
      technology, ovulation stimulation, or no treatment.
AB  - OBJECTIVE: To study birth outcomes among live born infants conceived by women who
      used infertility treatment. DESIGN: Population-based surveillance of women who
      recently delivered a live infant. SETTING: The birth outcomes among infants whose
      mothers used assisted reproductive technology (ART) or ovulation stimulation
      medications alone were compared with the outcomes of infants conceived without
      treatment. PATIENT(S): Stratified random sample of women who were attempting
      conception and gave birth to a live infant in six US states (n = 16,748).
      INTERVENTION(S): Assisted reproductive technology and ovulation stimulation. MAIN
      OUTCOME MEASURE(S): Adjusted odds ratios for perinatal outcomes. RESULT(S): The
      prevalence of infertility treatment use overall among women attempting conception
      was 10.9% (5.4% ART procedures, 5.5% ovulation stimulation medications).
      Singletons of mothers who received ART procedures were more likely to be born
      with low birthweight, preterm, and small for gestational age (SGA) than singleton
      infants conceived without treatment. Singleton infants of mothers who used
      ovulation stimulation medications alone were more likely to be SGA than singleton
      infants conceived without treatment. No differences were found between ART and no
      treatment twin infants. CONCLUSION(S): Among singleton infants, ART is associated
      with decreased fetal growth, decreased gestational length, and SGA; ovulation
      stimulation alone is associated with SGA.

PMID- 21718991
TI  - How many eggs are needed to produce an assisted reproductive technology baby: is
      more always better?
AB  - OBJECTIVE: To evaluate the association between the number of mature (metaphase II
      [MII]) oocytes per assisted reproductive technology (ART) cycle and the
      likelihood of live birth. DESIGN: Retrospective study. SETTING: Academic
      infertility practice. PATIENT(S): Seven hundred thirty-seven infertile women
      undergoing their initial fresh embryo, nondonor IVF or intracytoplasmic sperm
      injection cycle at Montefiore's Institute for Reproductive Medicine and Health
      between January 2002 and December 2008. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Live birth. RESULT(S): Two hundred twenty-four cycles resulted in a
      live birth (30.4%). Live birth cycles had significantly more MII oocytes obtained
      per cycle as compared with their unsuccessful counterparts (11.0 +/- 5.9 vs. 9.7
      +/- 6.2, respectively). Multivariate logistic regression was done to determine
      the minimum number of MII oocytes per cycle as a predictor of live birth after
      adjustment for age and historical maximum FSH values. Cycles that included the
      average number of MII in this cohort were used as a reference group. For cycles
      with five or fewer MII oocytes obtained, there was a statistically significant
      decrease in the likelihood of a live birth as compared with the reference group
      (odds ratio 0.61, 95% confidence interval 0.38-0.99). However, cycles with six or
      fewer obtained MII oocytes were not less likely to result in a live birth when
      compared with the reference group (odds ratio 0.69, 95% confidence interval 0.45
      1.08). CONCLUSION(S): In our cohort, there was an advantage to obtaining six or
      more MII oocytes during the fresh oocyte retrieval compared with five or fewer
      oocytes. There was not an advantage, however, to obtaining 10 or more or 15 or
      more oocytes as compared with obtaining 6-9 oocytes. The strategy of aiming for a
      greater number of oocytes in an ART cycle should be revisited.

PMID- 21718992
TI  - Cycle scheduling with oral contraceptive pills in the GnRH antagonist protocol vs
      the long protocol: a randomized, controlled trial.
AB  - OBJECTIVE: To compare cycle outcomes after scheduling with the standard long
      protocol versus the use of oral contraceptive pills (OCPs) in patients undergoing
      GnRH antagonist cycles. DESIGN: Prospective, randomized, controlled trial.
      SETTING: University-affiliated private assisted reproduction center. PATIENT(S):
      Regularly cycling women aged <=38 years with fewer than three previous IVF
      attempts were enrolled. Previous low responses to controlled ovarian
      hyperstimulation, ovarian surgery, or polycystic ovary were exclusion criteria.
      INTERVENTION(S): One hundred fifteen patients received OCP (0.030 ethinyl
      E(2)/0.15 desogestrel) for 12-16 days, and controlled ovarian hyperstimulation
      was started on day 5 after OCP treatment; similarly, 113 patients received the
      long protocol from day 20-22 of the previous cycle. MAIN OUTCOME MEASURE(S): The
      primary outcome was ongoing pregnancy rate; secondary outcome variables were
      clinical pregnancy rate, live birth rate, implantation rate, and miscarriage
      rate. RESULT(S): Patients receiving the GnRH antagonist treatment showed a lower
      peak serum E(2) (1,334 vs. 1,823 pg/mL) but similar peak serum PE (0.58 vs. 0.65
      ng/mL), lower duration of the stimulation (10.3 vs. 11.4 days) with similar FSH
      consumption (1,613 vs. 1,807 IU), and ovarian response (10.2 vs. 11.7 oocytes).
      No differences were observed in the fertilization rates (68.1% vs. 64.8%), total
      number of embryos obtained (5.9 vs. 6.2), mean number of embryos transferred (1.8
      vs. 1.8), implantation rate (36% vs. 39%), miscarriage rate (8.9% vs. 17%),
      ongoing pregnancy rate (47.8% vs. 53.9%), or live birth rate (44.3% vs. 47%).
      CONCLUSION(S): Comparable outcomes can be obtained using OCP containing 0.030
      ethinyl E(2)/0.15 desogestrel to schedule patients undergoing the antagonist
      protocol.

PMID- 21718993
TI  - Is it really the impact of controlled ovarian hyperstimulation on thyroid
      function?

PMID- 21718994
TI  - IVM media are designed specifically to support immature cumulus-oocyte complexes
      not denuded oocytes that have failed to respond to hyperstimulation.

PMID- 21718996
TI  - Ovarian salvage in bilaterally complicated severe ovarian hyperstimulation
      syndrome.
AB  - OBJECTIVE: To report the management of 2 cases of severe ovarian hyperstimulation
      syndrome (OHSS) bilaterally complicated by rupture and late subsequent torsion.
      DESIGN: Two case reports. SETTING: Obstetrics and Gynecology department of a
      hospital. PATIENT(S): Case 1: Severe OHSS complicated by massive intraperitoneal
      hemorrhage and bilateral extensive ovarian rents and rupture at multiple sites.
      Case 2: Twin IVF pregnancy and late severe OHSS complicated further by subsequent
      bilateral torsion. INTERVENTION(S): Case 1: Diagnosed by clinical, hematologic,
      and ultrasound findings. Resuscitation, laparotomy, and meticulous ovarian repair
      with suture, glue, and hemostat affected bilateral ovarian conservation. Case 2:
      Diagnosed clinically and confirmed by color Doppler. Left salpingoopherectomy was
      performed because of a devitalized left ovary; 3 days later laparoscopic right
      ovarian detorsion and aspiration was possible as early Doppler diagnosis was
      made. MAIN OUTCOME MEASURE(S): Case 1: ovarian conservation. Case 2: ovarian
      conservation and continuation of pregnancy. RESULT(S): Case 1: Recovery and
      normal serum FSH and E(2) 2 months postsurgery. Case 2: Continuation of pregnancy
      and the remaining ovary was healthy at abdominal delivery. CONCLUSION(S): Two
      cases of bilaterally complicated severe OHSS in which the patients' safety and
      bilateral ovarian integrity were at jeopardy. The cases are presented to define
      the importance of awareness, early diagnosis, and intervention, as well as the
      use of various methods and techniques to affect preservation of ovarian integrity
      and reserve.

PMID- 21718997
TI  - Priming in vitro maturation cycles with gonadotropins: salvage treatment for
      nonresponding patients.
AB  - OBJECTIVE: To compare the treatment outcomes in in vitro maturation (IVM) cycles
      primed with human menopausal gonadotropin with those for pure IVM cycles in
      patients with polycystic ovary syndrome. DESIGN: Prospective observational.
      SETTING: University-based tertiary medical center. PATIENT(S): Patients
      undergoing IVM cycles (primed IVM, 47; pure IVM, 118). INTERVENTION(S): IVM
      treatment with and without human menopausal gonadotropin stimulation. MAIN
      OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): The clinical pregnancy rate
      demonstrated a tendency toward improvement in the primed IVM group (53.1% vs.
      43.6%, 20.1% vs. 14.0% and 40.4% vs. 30.8%, [corrected] respectively) with better
      implantation and delivery rates (20.1% versus 14.4%; 95% confidence intervals 1.0
      3.06 and 40.4% versus 24.6%; 95% confidence intervals 0.1-0.8, respectively). We
      found no significant difference in pure IVM compared with primed IVM in the
      number of eggs collected, size of leading follicle, fertility rate, cleavage
      rate, and the number of embryos transferred. Total mature eggs and maturation
      rate were significantly higher in the group of pure IVM (11 +/- 2.1 versus 8.7 +/
      0.5 and 68.5% +/- 17.5% versus 60.9% +/- 0.4%, respectively). Importantly, the
      endometrial thickness was significantly improved in primed IVM cycles (7.9 +/-
      1.9 mm versus 7.1 +/- 0.8 mm), possibly leading to better implantation and
      pregnancy rates. CONCLUSION(S): Patients who fail to demonstrate endometrial or
      follicular growth during IVM cycles may benefit from gonadotropin priming during
      the same cycle.

PMID- 21718998
TI  - Comparison of hysterosalpingography and hysteroscopy in the evaluation of the
      uterine cavity in patients undergoing assisted reproductive techniques.
AB  - OBJECTIVE: To investigate the diagnostic value of hysterosalpingography (HSG) for
      intracavitary and structural uterine pathologies in comparison with hysteroscopy
      (HS) in patients undergoing intracytoplasmic sperm injection-embryo transfer and
      also to specify the patients who should be subjected to HS in the early stages of
      an infertility work-up. DESIGN: Retrospective analysis. SETTING: IVF unit of a
      university hospital. PATIENT(S): Three hundred fifty-nine consecutive women who
      underwent both HSG and HS for infertility investigation. INTERVENTION(S): HS and
      HSG. MAIN OUTCOME MEASURE(S): HS findings. RESULT(S): HSG shows a sensitivity of
      21.56%, specificity of 83.76%, positive predictive value of 55.26%, and negative
      predictive value of 70.75%. Its false-negative rate is 78.43%, and its false
      positive rate is 16.23%. Overall agreement between the two procedures is 68.9%.
      The risk of abnormal HS increases with advancing patient age and duration of
      infertility. Risk increments associated with patient age over 35 years and
      increasing number of previous assisted reproductive techniques (ART) persist even
      in the presence of a normal HSG. As expected, we encounter significantly less
      abnormal HS in the male factor infertility group. CONCLUSION(S): HS should be
      performed especially in patients older than 35 years of age and/or with a history
      of two or more previous ART trials even in the presence of a normal HSG. HSG
      shows unconvincing diagnostic value for intracavitary and structural uterine
      pathologies in infertility evaluation.

PMID- 21718999
TI  - Gynecologic use of Sepraspray Adhesion Barrier for reduction of adhesion
      development after laparoscopic myomectomy: a pilot study.
AB  - OBJECTIVE: To assess the safety and efficacy of Sepraspray Adhesion Barrier (a
      modified hyaluronic acid and carboxymethylcellulose powder) after laparoscopic
      surgery, in view of both the high efficacy of Seprafilm Adhesion Barrier in
      reducing postoperative adhesions after open surgical procedures and the
      difficulty with laparoscopic delivery. DESIGN: Multicenter, randomized, reviewer
      blinded trial. SETTING: Reproductive endocrinology and infertility clinics.
      PATIENT(S): Women undergoing laparoscopic myomectomy for indications including
      infertility. INTERVENTION(S): Randomization to treatment with (n = 21) or without
      (n = 20) Sepraspray Adhesion Barrier. MAIN OUTCOME MEASURE(S): Postoperative
      adhesions development was assessed at early second-look laparoscopy. Adhesions
      were scored using the modified American Fertility Society scoring system.
      RESULT(S): Surgical procedure duration length was 99 versus 102 minutes in the
      control versus Sepraspray Adhesion Barrier groups, respectively, with the median
      number of fibroids removed being two in each group and corresponding fibroid
      weights of 134 +/- 103 versus 113 +/- 161 g, respectively. Adhesions scores
      increased in both the control and Sepraspray Adhesion Barrier groups, with larger
      although nonstatistically significant increases noted in control subjects when
      evaluating for the anterior uterus, the posterior uterus, and the entire uterus.
      CONCLUSION(S): Laparoscopic application of Sepraspray Adhesion Barrier after
      myomectomy in this pilot study was associated with a trend toward a reduction in
      postoperative adhesion development, as well as an encouraging safety profile.
      Further evaluation is warranted. CLINICAL TRIAL NUMBER: Sepraspray Adhesion
      Barrier #NCT00624930.

PMID- 21719000
TI  - Incidence of endometriosis by study population and diagnostic method: the ENDO
      study.
AB  - OBJECTIVE: To estimate the incidence of endometriosis in an operative cohort of
      women seeking clinical care and in a matched population cohort to delineate more
      fully the scope and magnitude of endometriosis in the context of and beyond
      clinical care. DESIGN: Matched-exposure cohort design. SETTING: Surgical centers
      in the Salt Lake City, Utah, and San Francisco, California, areas. PATIENT(S):
      The operative cohort comprised 495 women undergoing laparoscopy/laparotomy
      between 2007 and 2009, and the population cohort comprised 131 women from the
      surgical centers' catchment areas. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Incidence of endometriosis by diagnostic method in the operative
      cohort and by pelvic magnetic resonance imaged (MRI) disease in the population
      cohort. RESULT(S): Endometriosis incidence in the operative cohort ranged by two
      orders of magnitude by diagnostic method: 0.7% for only histology, 7% for only
      MRI, and 41% for visualized disease. Endometriosis staging was skewed toward
      minimal (58%) and mild disease (15%). The incidence of MRI-diagnosed
      endometriosis was 11% in the population cohort. CONCLUSION(S): Endometriosis
      incidence is dependent on the diagnostic method and choice of sampling framework.
      Conservatively, 11% of women have undiagnosed endometriosis at the population
      level, with implications for the design and interpretation of etiologic research.

PMID- 21719001
TI  - Validation of a rapid alkaline hematin technique to measure menstrual blood loss
      on feminine towels containing superabsorbent polymers.
AB  - OBJECTIVE: To validate the semiautomated alkaline hematin technique for rapid
      measurement of menstrual blood loss on ultrathin sanitary towels with a
      superabsorbent polymer component. DESIGN: Laboratory study using simulated
      menstrual fluid (SMF) and Always Ultra Normal, Long, and Night "with wings"
      sanitary towels. SETTING: Laboratorium fur Klinische Forschung, Germany.
      PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Linearity and
      blood recovery over a range of SMF volumes applied to towels, the lower limit of
      reliable detection, and the effect of storing soiled towels for up to 5 weeks at
      20 degrees C and 4 degrees C before analysis, were determined. Recovery from 63
      SMF samples comprising between 5% to 100% blood and 0.05-35 mL applied volume was
      compared with duplicates analyzed at Keele Menstrual Disorders Laboratory (manual
      reference method). RESULT(S): Linearity was confirmed, and >=85% recovery was
      reproducibly achieved at up to 30 mL applied blood at all tested SMF
      compositions, except at low volume or high dilution equivalent to <4 mL blood.
      Samples could be stored for 3 weeks at 4 degrees C without loss of recovery.
      Linear regression analysis showed good agreement with the reference method.
      CONCLUSION(S): The semiautomated alkaline hematin technique is a reliable method
      for measuring menstrual blood loss from Always Ultra sanitary towels containing
      superabsorbent polymers.

PMID- 21719002
TI  - A laparoscopic approach to Nuck's duct endometriosis.
AB  - OBJECTIVE: To report a case of uncommon endometriosis located in the Nuck's duct
      and its laparoscopic resolution. DESIGN: Case report. SETTING: Gynecologic
      department at 12 de Octubre University Hospital, Madrid. PATIENT(S): A 35-year
      old woman, gravida 1 para 1, presented with an inguinal right mass. She had a
      right nephrectomy because of acute pyelonephritis. Computed tomography showed a
      cystic lesion that was suggestive of a Nuck's duct cyst. Fine-needle aspiration
      cytology was performed, and endometriosis was determined. INTERVENTION(S): Cyst
      removal and closure of the internal inguinal ring's defect by the laparoscopic
      approach. MAIN OUTCOME MEASURE(S): Disease free. RESULT(S): The intervention was
      successfully performed by laparoscopic approach. The postoperative evolution was
      good, and the patient was discharged 2 days after surgery. CONCLUSION(S):
      Inguinal or Nuck's duct are both uncommon locations for endometriosis; therefore,
      it is difficult to suspect in patients without a surgical history. Once
      identified, the treatment involves removal of the endometrioma and repair of the
      internal inguinal ring. A laparoscopic approach should be considered when
      possible.

PMID- 21719003
TI  - Serum beta human chorionic gonadotropin levels can inform outcome counseling
      after in vitro fertilization.
AB  - The predictive value of serum beta hCG level for fetal cardiac motion and
      pregnancy outcome after IVF was evaluated. The serum hCG level 12 days after ET
      is a useful predictor of subsequent presence of fetal cardiac activity and live
      birth and may assist clinicians in counseling patients regarding their IVF
      outcome.

PMID- 21719004
TI  - Parasitic myomas after laparoscopic surgery: an emerging complication in the use
      of morcellator? Description of four cases.
AB  - OBJECTIVE: To report the development of parasitic myomas after the use of a
      morcellator. DESIGN: Retrospective study. SETTING: Tertiary care referral center
      for the treatment of benign gynecologic pathologies. PATIENT(S): Women undergoing
      surgery for uterine fibroids. INTERVENTION(S): Chart review. MAIN OUTCOME
      MEASURE(S): Presence of parasitic leiomyomas. RESULT(S): We identified four cases
      of parasitic myomas over the 3-year study period. Two out of the four were
      symptomatic. The prevalence of this complication, considering all women with whom
      the electric morcellator was used (n = 423) was 0.9% (95% CI, 0.3-2.2%).
      Considering exclusively the women who underwent myomectomy (n = 321), it was 1.2%
      (95% CI, 0.4-2.9%). CONCLUSION(S): Laparoscopic myomectomy with the use of a
      morcellator is associated with an increased risk of developing of parasitic
      myomas. A thorough inspection and washing of the abdominopelvic cavity at the end
      of the surgery should be performed to prevent this rare complication.

PMID- 21719005
TI  - Serum anti-Mullerian hormone and inhibin B concentrations are not useful
      predictors of ovarian response during ovulation induction treatment with
      recombinant follicle-stimulating hormone in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To describe changes of anti-Mullerian hormone (AMH) and inhibin B
      during low-dose gonadotropin ovulation induction (OI) treatment in women with
      polycystic ovary syndrome (PCOS), and thus disturbed selection of the dominant
      follicle. DESIGN: Observational study. SETTING: A referral fertility clinic.
      PATIENT(S): Women with PCOS (n = 48) and normo-ovulatory women (n = 23).
      INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): Serum AMH, inhibin B, FSH, and E(2)
      concentrations were measured at start of stimulation, on the day of follicle
      selection, and at administration of hCG during OI cycles and were compared with
      concentration measured during the normal menstrual cycle. RESULT(S): Development
      of a single dominant follicle was observed in 92% of all OI cycles, reflected by
      similar E(2) concentrations compared with those in spontaneous cycles. AMH
      concentrations were constant during low-dose ovarian stimulation. Inhibin B
      concentrations remained elevated in patients with PCOS, suggesting prolonged
      survival of small antral follicles, whereas in controls inhibin B concentrations
      declined during the late follicular phase. CONCLUSION(S): The lack of change in
      AMH and inhibin B concentrations suggest that follicle dynamics during low-dose
      stimulation seem different from those during controlled ovarian hyperstimulation.
      In addition, constant AMH and inhibin B levels suggest that neither AMH nor
      inhibin B is an accurate marker of ovarian response after low-dose gonadotropin
      OI in patients with PCOS.

PMID- 21719006
TI  - Enzymatic isolation of human primordial and primary ovarian follicles with
      Liberase DH: protocol for application in a clinical setting.
AB  - OBJECTIVE: To set up a protocol to isolate human preantral follicles with an
      enzyme produced in good manufacturing practice conditions for use in a clinical
      setting. DESIGN: For follicle isolation, ovarian biopsies were divided into two
      halves: one was treated with collagenase IA and the other with Liberase DH
      (Dispase High) Research Grade. SETTING: Academic research unit. PATIENT(S):
      Twelve women undergoing laparoscopy for benign gynecological disease.
      INTERVENTION(S): Follicle isolation. MAIN OUTCOME MEASURE(S): Follicles were
      counted, their morphology was analyzed, and follicular viability was evaluated by
      live/dead assays before and after 7 days of in vitro culture. Their structural
      preservation was assessed after isolation by electron microscopy. RESULT(S): A
      total of 1,030 follicles were obtained after isolation: 566 with Liberase DH and
      464 with collagenase IA. The percentage of viable follicles (with <10% of dead
      granulosa cells [GC]) was not found to be statistically different before or after
      culture in either group (Liberase DH: 95% and 81%, respectively; collagenase: 96%
      and 87%, respectively). A significant increase in follicle size was observed in
      both groups after culture. Liberase DH did not affect the ultrastructure of
      isolated follicles. CONCLUSION(S): Liberase DH allows isolation of a high number
      of preantral follicles, maintaining their viability, even after in vitro culture,
      and their ultrastructure. In addition, Liberase DH can be produced in good
      manufacturing practice conditions, allowing use of isolated preantral follicles
      for future clinical applications.

PMID- 21719007
TI  - Ovarian function in Duarte galactosemia.
AB  - OBJECTIVE: To determine if girls with Duarte variant galactosemia (DG) have an
      increased risk of developing premature ovarian insufficiency based on prepubertal
      anti-Mullerian hormone (AMH) levels. DESIGN: Cross-sectional study. SETTING:
      University research laboratory. PATIENT(S): Study volunteers included 57 girls
      with DG, 89 girls with classic galactosemia (GG), and 64 control girls between
      the ages of <1 month and 10.5 years. INTERVENTION(S): Blood sampling. MAIN
      OUTCOME MEASURE(S): We determined AMH and FSH levels in study volunteers with and
      without Duarte variant or GG. RESULT(S): FSH levels were significantly higher and
      AMH levels significantly lower in girls with GG than in age-stratified control
      girls, but there was no significant difference between FSH and AMH levels in
      girls with DG and control girls. CONCLUSION(S): Although >80% of girls with GG in
      this study demonstrated low to undetectable AMH levels consistent with diminished
      ovarian reserve, 100% of girls with DG in our study demonstrated no apparent
      decrease in AMH levels or increase in FSH levels, suggesting that these girls are
      not at increased risk for premature ovarian insufficiency.

PMID- 21719008
TI  - Variations in car crash-related hospitalization costs amongst young adults in New
      South Wales, Australia.
AB  - BACKGROUND: This study aims to examine factors associated with variation in crash
      related hospitalization costs for young adults in New South Wales (NSW),
      Australia with a particular focus on types of vehicle occupant, rurality of
      residence and socioeconomic status (SES). METHODS: Data on patients aged 17-25
      years, admitted to public hospitals due to a crash during July 2000-June 2007
      were extracted from the NSW Health Admission Collection database. The
      hospitalization cost of each admission was calculated based on published charges
      for specific Australian Refined-Diagnosis Related Groups (AR-DRG). Multivariable
      analyses using generalized estimating equations were used to estimate costs by
      vehicle occupant type (driver, passenger and other occupants), rurality of
      residence (urban, regional and rural areas) and SES (low, moderate and high SES
      areas). RESULTS: During 2000-2007, there were 11,892 crash-related
      hospitalizations involving young adults, aged 17-25 years, in NSW. These cost the
      health sector about A$87.6 million or on average, A$7363 per hospitalization
      (mean length of stay (LOS) 5.3 days). Compared to drivers, passengers had
      significantly longer LOS (<0.01) as well as higher hospitalization costs (p =
      0.04). Regional and rural young adults had significantly longer LOS and higher
      hospitalization costs compared to urban young adults (p<0.05). Compared with
      young adults from high SES areas, young adults from moderate SES areas had
      significantly higher costs (p = 0.02), whilst the higher costs for young adults
      of low SES areas was borderline significant (p = 0.06), although differences in
      LOS by SES were not significant. CONCLUSION: Annually, young adults' crashes in
      NSW were estimated to cost the health sector at least A$14.6 million between 2001
      and 2007. The higher hospitalization costs and LOS for young adults living in
      regional and rural vs. urban areas, and those living in moderate and low SES vs.
      high SES areas partly reflects the severity of these crashes and challenges for
      treatment. Based on these findings, a strong economic argument can be made for
      targeting prevention strategies to young people living in rural and low SES
      areas. The area variations in costs also suggest some scope for policy makers to
      consider potentially more efficient ways of targeting both treatment and
      preventative programmes.

PMID- 21719009
TI  - Early fasciotomy in patients with extremity vascular injury is associated with
      decreased risk of adverse limb outcomes: a review of the National Trauma Data
      Bank.
AB  - INTRODUCTION AND OBJECTIVES: Lower extremity (LE) arterial trauma and its
      treatment may lead to extremity compartment syndrome (ECS). In that setting, the
      decision to perform fasciotomies is multifactoral and is not well delineated. We
      evaluated the outcomes of patients with surgically treated LE arterial injury who
      underwent early or delayed fasciotomies. METHODS: The National Trauma Data Bank
      (NTDB) was retrospectively reviewed for patients who had LE arterial trauma and
      underwent both open vascular repair and fasciotomies. Exclusion criteria were
      additional non-LE vascular trauma, head or spinal cord injuries, crush injuries,
      burn injuries, and declaration of death on arrival. Patients were divided into
      those who had fasciotomies performed within 8h (early group) or >8h after open
      vascular repair (late group). Comparative analyses of demographics, injury
      characteristics, complications, and outcomes were performed. RESULTS: Of the 1469
      patient admissions with lower extremity arterial trauma that met inclusion
      criteria there were 612 patients (41.7%) who underwent fasciotomies. There were
      543 and 69 patients in the early and late fasciotomy groups, respectively. There
      was no significant difference in age, injury severity, mechanism of injury,
      associated injuries, and type of vascular repair between the groups. A higher
      rate of iliac artery injury was observed in the late fasciotomy group (23.2% vs.
      5.9%, P<.001). Patients in the early fasciotomy group had lower amputation rate
      (8.5% vs. 24.6%, P<.001), lower infection rate (6.6% vs. 14.5%, P = .028) and
      shorter total hospital stay (18.5 +/- 20.7 days vs. 24.2 +/- 14.7 days, P = .007)
      than those in the late fasciotomy group. On multivariable analysis, early
      fasciotomy was associated with a 4-fold lower risk of amputation (Odds Ratio
      0.26, 95% CI 0.14-0.50, P<.0001) and 23% shorter hospital LOS (Means Ratio 0.77,
      95% CI 0.64-0.94, P = .01). CONCLUSION: Early fasciotomy is associated with
      improved outcomes in patients with lower extremity vascular trauma treated with
      surgical intervention. Our findings suggest that appropriate implementation of
      early fasciotomy may reduce amputation rates in extremity arterial injury.

PMID- 21719010
TI  - Fertility desires and the feasibility of contraception counseling among genital
      fistula patients in eastern Democratic Republic of the Congo.
AB  - OBJECTIVE: To determine the fertility and contraceptive desires of genital
      fistula patients in eastern Democratic Republic of the Congo (DRC) and to
      evaluate the impact of contraceptive counseling and its effect on contraceptive
      knowledge and use. METHODS: Group contraceptive counseling was offered to fistula
      patients at HEAL Africa Hospital between February and May 2010. Fertility desires
      and contraceptive knowledge were assessed via verbally administered
      questionnaires before and after counseling, and use of modern contraceptive
      methods was tracked. RESULTS: Of the 61 participants, 22/34 (64.7%) of those who
      desired children wanted to wait at least 1 year after repair before attempting
      pregnancy. Overall, 31/58 (53.4%) women had heard of birth control, although only
      15 (24.6%) knew any specific methods, and none had ever used contraception. After
      counseling, all participants could recall 1 or more methods. Of the 25
      participants discharged over the subsequent 3 months, 5 (20.0%) and 3 additional
      fistula patients selected a modern method of contraception. CONCLUSION: Desire
      for contraception and birth spacing among women with fistula is significant.
      Basic group contraception counseling and access are feasible and lead to
      increased contraceptive knowledge and use.

PMID- 21719011
TI  - Prevalence of abnormal glucose metabolism in a cohort of Arab women with
      polycystic ovary syndrome.

PMID- 21719012
TI  - Effect of combined spinal-epidural analgesia versus epidural analgesia on labor
      and delivery duration.
AB  - OBJECTIVE: To determine whether combined spinal-epidural analgesia (CSEA) can
      decrease the known epidural effect of lengthening delivery. METHODS: Between
      April and May 2010, 144 women undergoing childbirth in hospital with epidural
      pain relief were randomized to receive either low-dose epidural analgesia (LEA)
      or CSEA. The spinal component included 2.5mg of bupivacaine, 25 MUg of fentanyl,
      and 200 MUg of morphine. The epidural component of the CSEA procedure was started
      once pain returned. The primary outcome was total labor duration measured from
      the time of initiation of labor analgesia to delivery. RESULTS: The difference in
      duration between LEA (n=72) and CSEA (n=72) was 5 minutes for labor (P=0.82), 2
      minutes for delivery (P=0.60), and 7 minutes for total labor duration (P=0.75).
      The combined group used less levobupivacaine (P<0.001) and had lower sensory
      blockade at the dermatomal level (P=0.037). Women in the CSEA group had a higher
      incidence of pruritus (P=0.002) and lightheadedness (P=0.02) during labor; and a
      higher incidence of pruritus (P=0.002), nausea-vomiting (P=0.026), and drowsiness
      (P=0.003) in the postpartum period. CONCLUSION: As compared with LEA, CSEA did
      not shorten the duration of labor length; however, it did reduce levobupivacaine
      consumption and motor weakness.

PMID- 21719013
TI  - Retinal detachment in association with pre-eclampsia, eclampsia, and HELLP
      syndrome.
AB  - OBJECTIVE: To review case reports of retinal detachment in women with pre
      eclampsia/eclampsia. METHODS: Medline was searched for case reports of retinal
      detachment associated with pre-eclampsia/eclampsia. Articles written in English,
      Spanish, or Portuguese and published between 1990 and 2010 were reviewed.
      RESULTS: A total of 28 cases of retinal detachment were identified; 15 were
      associated with severe pre-eclampsia (3 of these probably had hemolysis, elevated
      liver enzymes, and low platelets [HELLP] syndrome), 9 with HELLP syndrome, 2 with
      eclampsia, and 2 with both HELLP syndrome and eclampsia. The majority (60%) of
      women were nulliparous, 4 had abruptio placentae, and cesarean delivery was
      performed in 76%. Retinal detachment was bilateral in 89% and associated with
      delivery of the fetus in 96%; 69% were diagnosed postpartum. Within 2-12 weeks
      postpartum, all patients had complete recovery of vision with clinical
      management. CONCLUSION: Retinal detachment in pre-eclampsia/eclampsia might be
      associated with HELLP syndrome, indicating that microangiophatic hemolysis might
      have a role in the pathophysiology of retinal detachment. Its occurrence might
      not be correlated with the severity of pre-eclampsia because pre-eclampsia is a
      constellation of signs and symptoms (persistent vasospasms with hemolysis and
      hypoalbuminemia) rather than simply being hypertension.

PMID- 21719014
TI  - Effect of phytosterols and their oxidation products on lipoprotein profiles and
      vascular function in hamster fed a high cholesterol diet.
AB  - Human diets contain phytosterols and their oxidation products. We investigated
      effect of beta-sitosterol (Si), stigmasterol (St), beta-sitosterol oxidation
      products (SiOP) and stigmasterol oxidation products (StOP) on plasma total
      cholesterol and their interaction with the gene expression of enzymes, proteins
      and transporters involved in cholesterol absorption and metabolism. Sixty male
      hamsters were fed the control diet or one of four experimental diets containing
      0.1% Si, 0.1% SiOP, 0.1% St and 0.1% StOP, respectively, for six weeks. SiOP and
      StOP groups had the relative liver weights greater than their corresponding non
      oxidized forms, indicating they were possibly toxic. Results showed both Si and
      St groups reduced while SiOP and StOP hamsters lost the capacity of lowering
      plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL) and
      triacylglycerols (TG) compared with the control group. Si and St but not SiOP and
      StOP were anti-atherosclerotic. RT-PCR analysis demonstrated Si and St but not
      SiOP and StOP down-regulated mRNA levels of intestinal acyl CoA: cholesterol
      acyltransferase (ACAT2) and microsomal triglyceride protein (MTP). Aortas from Si
      and St hamsters relaxed better than those from the control and their
      corresponding SiOP and StOP-treated hamsters. It was concluded that Si and St not
      SiOP and StOP were beneficial in improving lipoprotein profile and aortic
      function.

PMID- 21719015
TI  - Minocycline reduces plaque size in diet induced atherosclerosis via p27(Kip1).
AB  - OBJECTIVE: Minocycline, a tetracycline derivate, mediates vasculoprotective
      effects independent of its antimicrobial properties. Thus, minocycline protects
      against diabetic nephropathy and reduces neointima formation following vascular
      injury through inhibition of apoptosis or migration, respectively. Whether
      minocycline has an effect on primary atherogenesis remains unknown. METHODS:
      Using morphological and immunohistochemical analyses we determined de novo
      atherogenesis in ApoE-/- mice receiving a high fat diet (HFD) with or without
      minocycline treatment. The effect of minocycline on proliferation, expression of
      p27(Kip1) or PARP-1 (Poly [ADP-ribose] polymerase 1), or on PAR (poly ADP
      ribosylation) modification in vascular smooth muscle cells (VSMC) was analyzed in
      ex vivo and in vitro (primary human and mouse VSMC). RESULTS AND CONCLUSION:
      Minocycline reduced plaque size and stenosis in ApoE-/- HFD mice. This was
      associated with a lower number and less proliferation of VSMC, reduced PAR (poly
      ADP-ribosylation) modification and increased p27(Kip1) expression within the
      plaques. In agreement with the ex vivo data minocycline reduced proliferation,
      PARP-1 expression, PAR modification while inducing p27 expression in human and
      mouse VSMC in vitro. These effects were observed at a low minocycline
      concentration (10 MUM), which had no effect on VSMC migration or apoptosis.
      Minocycline inhibited PARP-1 and induced p27(Kip1) expression in VSMC as
      efficiently as the specific PARP-1 inhibitor PJ 34. Knock down of p27(Kip1)
      abolished the antiproliferative effect of minocycline. These data establish a
      novel antiatherosclerotic mechanism of minocycline during de novo atherogenesis,
      which depends on p27(Kip1) mediated inhibition of VSMC proliferation.

PMID- 21719016
TI  - Frailty assessment based on wavelet analysis during quiet standing balance test.
AB  - BACKGROUND: A standard phenotype of frailty was independently associated with an
      increased risk of adverse outcomes including comorbidity, disability and with
      increased risks of subsequent falls and fractures. Postural control deficit
      measurement during quiet standing has been often used to assess balance and fall
      risk in elderly frail population. Real time human motion tracking is an accurate,
      inexpensive and portable system to obtain kinematic and kinetic measurements. The
      aim of this study was to examine orientation and acceleration signals from a tri
      axial inertial magnetic sensor during quiet standing balance tests using the
      wavelet transform in a frail, a prefail and a healthy population. METHODS:
      Fourteen subjects from a frail population (79+/-4 years), eighteen subjects from
      a prefrail population (80+/-3 years) and twenty four subjects from a healthy
      population (40+/-3 years) volunteered to participate in this study. All signals
      were analyzed using time-frequency information based on wavelet decomposition and
      principal component analysis. FINDINGS: The absolute sum of the coefficients of
      the wavelet details corresponding to the high frequencies component of
      orientation and acceleration signals were associated with frail syndrome.
      INTERPRETATION: These parameters could be of great interest in clinical settings
      and improved rehabilitation therapies and in methods for identifying elderly
      population with frail syndrome.

PMID- 21719017
TI  - Markerless analysis of front crawl swimming.
AB  - Research on motion analysis of swimmers is commonly based on video recordings of
      the subject's motion, which are analyzed by manual digitization of feature points
      by an operator. This procedure has two main drawbacks: it is time-consuming, and
      it is affected by low repeatability. Therefore, the application of video-based,
      automatic approaches to motion analysis was investigated. A video-based,
      markerless system for the analysis of arm movements during front crawl swimming
      was developed. The method proposed by Corazza et al. (2010) was modified in order
      to be used into water environment. Three dimensional coordinates of shoulder,
      elbow and wrist joints centers of 5 sprint swimmers performing front crawl
      swimming were determined. Wrist joint velocity was also calculated. Accuracy and
      reliability of the proposed technique were evaluated by means of comparison with
      traditional manual digitization (SIMI Reality Motion Systems GmbH). Root mean
      square distance (RMSD) values between trajectories estimated with the two
      techniques were determined. Results show good accuracy for wrist joint
      (RMSD<56mm), and reliability, evaluated on one subject, comparable to the inter
      operator variability associated with the manual digitization procedure. The
      proposed technique is therefore very promising for quantitative, wide-scale
      studies on swimmers' motion.

PMID- 21719018
TI  - Lateral wedges decrease biomechanical risk factors for knee osteoarthritis in
      obese women.
AB  - Obesity is the primary risk factor for the development and progression of medial
      compartment knee osteoarthritis. Laterally wedged insoles can reduce many of the
      biomechanical risk factors for disease development in osteoarthritis patients and
      lean individuals but their efficacy is unknown for at-risk, obese women. The
      purpose was to determine how an 8 degrees  laterally wedged insole influenced
      kinetic and kinematic gait parameters in obese women. Gait analysis was performed
      on fourteen obese (average 29.3 years; BMI 37.2kg/m(2)) and 14 lean control women
      (average 26.1 years; BMI 22.4kg/m(2)) with and without a full-length, wedged
      insole. Peak joint angles, the external knee adduction moment and its angular
      impulse were calculated during preferred and standard 1.24m/s walking speeds.
      Statistical significance was assessed using a 2-way ANOVA (alpha=0.05). The
      insole significantly reduced the peak external knee adduction moment (mean
      decrease of 3.6+/-3.9Nm for obese and 1.9+/-1.8Nm for controls) and its angular
      impulse in both groups. The wedged insoles also produced small changes in ankle
      dorsiflexion (obese: 1.2+/-1.4 degrees  increase; control: 1.5+/-1.4 degrees 
      increase) and eversion range of motion (obese: 1.3+/-1.9 degrees  decrease;
      control: 1.5+/-1.2 degrees  decrease) but did not alter peak angles of superior
      joints. Although the majority of obese women may develop knee osteoarthritis
      during their lifetime, a prophylactic insole intervention could allow obese women
      with no severe knee malalignments to be active while preventing or delaying
      disease onset. However, the long-term effects of the insole have not yet been
      examined.

PMID- 21719019
TI  - High-capacity composite adsorbents for nucleic acids.
AB  - CytoporeTM is a bead-shaped, macroporous and easily compressible cellulose-based
      anion-exchange material intended for cultivation of anchor-dependent animal
      cells. Reticulated vitreous carbon (RVC) is a strong, non-compressible, high
      voidage (97%) matrix material that can be cut to desired geometrical shapes.
      Cytopore and RVC were combined to cylindrical composites (25 mm * 10 mm) fitted
      inside chromatography columns. The composite combined the advantageous properties
      of both its constituents, making it suitable for column chromatography. The
      composite could withstand very high flow rates without compaction of the bed (>25
      column volumes/min; 4000 cm h(-1)). Chromatography runs with tracers showed a low
      HETP value (0.3mm), suggesting that pore flow was in operation. The dynamic
      binding capacities (10% breakthrough) per gram of dry weight Cytopore were
      determined for several compounds including DNA and RNA and were found to be 240
      370 mg/g. The composite was used to isolate pUC 18-type plasmids from a cleared
      alkaline lysate in a good yield. Confocal microscopy studies showed that plasmids
      were bound not only to the surface of the Cytopore material but also within the
      matrix walls, thus offering an explanation to the very high binding capacities
      observed. The concept of using a composite prepared from a mechanically weak,
      high-binding material and a strong scaffold material may be applied to other
      systems as well.

PMID- 21719020
TI  - Monodisperse red blood cell-like particles via consolidation of charged droplets.
AB  - Recently, researchers have tried to produce non-spherical and anisotropic
      particles to be used in the next generation of multi-functional materials. Of key
      interest is the red blood cell-like particle. The torus structure was produced
      under the relatively fast consolidation of monodisperse droplets, and its
      parameters were found to be tunable by temperature as well as solvent type and
      concentration. The observation of consolidation demonstrated that the polymers
      were accumulated and solidified in the torus structure, naturally, whereas there
      was the critical droplet size to induce the asymmetry diffusivities. The torus
      structures could be simply tuned by the flow rate and concentration. The coaxial
      nozzle system produced the core/shell torus particles. These results state that
      the consolidation mechanism can hold important clues to enhance the range of
      tuning capabilities.

PMID- 21719021
TI  - Monodisperse sub-10 nm gold nanoparticles by reversing the order of addition in
      Turkevich method--the role of chloroauric acid.
AB  - The Turkevich method for synthesizing gold nanoparticles, using sodium citrate as
      the reducing agent, is renowned for its ability to produce biocompatible colloids
      with mean size >10 nm. Here we show that monodisperse gold nanoparticles in the 5
      10 nm size range can be synthesized by simply reversing the order of addition of
      reactants, i.e. adding chloroauric acid to citrate solution. Kinetic studies and
      electron microscopic characterization revealed that the reactivity of chloroauric
      acid, initial molar ratio of citrate to chloroauric acid (MR), and reaction
      mixture pH play an important role in producing monodisperse gold nanoparticles.
      Reversing the order of addition also enhanced the stabilization of nanoparticles
      at high MR values. Remarkably, the system exhibits a 'memory' of the order of
      addition, even when the timescale of mixing is much shorter than the timescale of
      synthesis.

PMID- 21719022
TI  - Slightly surface-functionalized polystyrene microspheres prepared via Pickering
      emulsion polymerization using for electrophoretic displays.
AB  - Slightly surface-functionalized polystyrene (PS) microspheres are prepared by
      photocatalytic Pickering emulsion polymerization using sodium styrene sulfonate
      (SSS)-modified titania hydrosol as a stabilizer. Aqueous electrophoresis
      measurements indicate the adsorption of bifunctional SSS anions on the surface of
      titania nanoparticles via electrostatic interaction. SSS molecules participate in
      the copolymerization with the monomers before the nucleation and thus have a
      great effect on the morphology and surface structure of the obtained PS
      microspheres. Appropriate SSS concentration leads to PS microspheres with small
      size, narrow distribution, and uniform surface chemistry. This kind of polymer
      particles can be used as a good candidate for the electrophoretic displays
      because of their high colloidal stability and electrophoretic mobility in the
      apolar solvent.

PMID- 21719023
TI  - Highly ordered macroporous carbon spheres and their catalytic application for
      methanol oxidation.
AB  - Highly ordered three dimensionally macroporous carbon spheres (3DMPCS) were
      successfully prepared against removable colloidal silica crystal bead templates
      by carbonization of glucose. The unique structural characteristics of the well
      developed three dimensionally interconnected macropores were characterized by
      scanning electron microscopy, transmission electron microscopy, X-ray
      diffraction, and nitrogen adsorption. The 3DMPCS have uniform large pore
      structures with size about 250 nm. Pt nanoparticles were supported on the
      macroporous carbon spheres by two aqueous impregnation methods, and it was found
      that the 3DMPCS supported Pt exhibited high electrocatalytic activity for
      methanol oxidation.

PMID- 21719024
TI  - Investigation of interfacial and structural properties of CTAB at the oil/water
      interface using dissipative particle dynamics simulations.
AB  - We have used dissipative particle dynamics (DPD) to simulate the system of
      cetyltrimethylammonium bromide (CTAB) monolayer at the oil/water interface. The
      interfacial properties (interfacial density, interfacial thickness, and
      interfacial tension), structural properties (area compressibility modulus, end to
      end distance, and order parameter), and their dependence on the oil/water ratio
      and the surfactant concentration were investigated. Three different
      microstructures, spherical oil in water (o/w), interfacial phase, and water in
      oil (w/o), can be clearly observed with the oil/water ratio increasing. Both the
      snapshots and the density profiles of the simulation show that a well defined
      interface exists between the oil and water phases. The interface thickens with
      CTAB concentration and oil/water ratio. The area compressibility modulus
      decreases with an increase in the oil/water ratio. The CTAB molecules are more
      highly packed at the interface and more upright with both concentration and
      oil/water ratio. The root mean square end-to-end distance and order parameter
      have a very weak dependence on the oil/water ratio. But both of them show an
      increase with CTAB concentration, indicating that the surfactant molecules at the
      interface become more stretched and more ordered at high concentration. As CTAB
      concentration increases further, the order parameter decreases instead because
      the bending of the interface. At the same time, it is shown that CTAB has a high
      interfacial efficiency at the oil/water interface.

PMID- 21719025
TI  - Effect of dissolved organic matter from Guangzhou landfill leachate on sorption
      of phenanthrene by montmorillonite.
AB  - To investigate the effect of dissolved organic matter (DOM) on the adsorption of
      phenanthrene (PHE) by montmorillonite (MMT), organic clay complex was prepared by
      associating montmorillonite with DOM extracted from landfill leachate. Both the
      raw MMT, DOM, and MMT complex (DOM-MMT) were characterized by X-ray diffraction
      (XRD), Fourier transform infrared (FTIR), X-ray photo-emission spectroscopy
      (XPS), and scanning electron microscope (SEM). Batch adsorption studies were
      carried out on the adsorption of PHE as a function of contact time, temperature,
      and adsorbent dose. The sorption of PHE on complex was rapid, and the kinetics
      could be described well by the Pseudo-first-order model (R(2)>0.99), with an
      equilibrium time of 120 min. The adsorption isotherm was in good agreement with
      the Henry equation and Freundlich equation. Also, thermodynamic studies showed
      that the adsorption process was exothermic and spontaneous in nature. Compared
      with MMT, the adsorption capacity of DOM-MMT complex for PHE was greatly
      enhanced. The effects of DOM on PHE sorption by MMT may be attributed to the
      changes in the surface structure, the specific surface area, the hydrophobic
      property, and the average pore size of MMT. A series of atomistic simulations
      were performed to capture the structural and functional qualities observed
      experimentally.

PMID- 21719026
TI  - Electrokinetic properties of wavellite and its floatability with cationic and
      anionic collectors.
AB  - The reverse apatite flotation with fatty acids has been widely used for the
      reduction of phosphorus content of magmatic origin iron ores. However, the
      occurrence of phosphorus intensely disseminated as secondary minerals such as
      wavellite renders the anionic reverse flotation a challenge. Zeta potential
      measurements and microflotation tests of wavellite with the use of anionic and
      cationic collectors were carried out in this work. The wavellite's IEP value was
      achieved at pH 4.5. Below the IEP value, the surface positively charged sites are
      made up of aluminum ions. The species H(+), Al(OH)(2)(+), Al(OH)(2+), Al(3+), OH(
      ), H(2)PO(4)(-), HPO(4)(2-), and PO(4)(3-) play a role in the protonation and
      deprotonation reactions that will determine the wavellite-solution interface
      properties. The highest values of wavellite's floatability under basic pH
      conditions were achieved in the presence of cationic collectors (1 * 10(-4) mol
      L(-1)). The formation of surface complexes and the precipitation of insoluble
      salt of aluminum onto wavellite surface seems to be the most likely hypothesis
      for the chemical nature interactions between amines and wavellite. The surface
      formation of aluminum oleate on the wavellite's surface seems to be the most
      probable hypothesis for the adsorption mechanism and the resultant high
      floatability of wavellite between pH 7.5 and pH 10.0 in the presence of sodium
      oleate (1 * 10(-4) mol L(-1)). The results showed that the cationic reverse
      flotation of secondary phosphates is a promising route to reduce the phosphorus
      content of iron ores from deposits that underwent a supergene enrichment process,
      since wavellite floatability in the alkaline pH range, using amine as collector,
      was not significantly affected by the presence of corn starch.

PMID- 21719027
TI  - Auditory discrimination as a condition for E-learning based Speech Therapy: a
      proposal for an auditory discrimination test (ADT) for adult dysarthric speakers.
AB  - BACKGROUND: Web based speech training for dysarthric speakers, such as E-learning
      based Speech Therapy (EST), puts considerable demands on auditory discrimination
      abilities. AIMS: To discuss the development and the evaluation of an auditory
      discrimination test (ADT) for the assessment of auditory speech discrimination
      skills in Dutch adult dysarthric speakers as a prelude to EST. METHOD: Five ADT
      subtests were developed, each addressing a vital speech dimension in speech
      therapy: articulation (segmental elements), intensity, overall pitch, speech rate
      and intonation. A healthy control group of 36 participants performed a 'same
      different task' in each subtest. ADT items yielding scores of at least 80% but
      below 100% correctly responding healthy controls were considered sensitive to
      diminished auditory discrimination. Subsequently, the ADT was carried out by 14
      neurological patients with dysarthric speech and 14 matched healthy controls.
      Score percentages, sensitivity indices and reaction times (ms) on only sensitive
      items were compared. RESULTS: The majority of the ADT items met the 'minimal 80%
      to below 100% criterion' in the healthy control group. The neurological
      participants performed lower on all outcome measures across all subtests than the
      healthy controls, although not all of these differences achieved statistical
      significance. CONCLUSIONS: The results of the healthy control group show that the
      majority of the ADT items meet our criterion for sensitivity to diminished
      auditory discrimination. The poorer performance of dysarthric patients across all
      subtests supports the sensitivity of the ADT. However, further research involving
      larger and more homogeneous groups of neurological patients is required. LEARNING
      OUTCOMES: Readers will be encouraged to (1) identify potential factors that may
      hinder web based speech training and (2) estimate the value of assessing auditory
      discrimination skills as a vital condition for (web based) speech training in
      dysarthric patients.

PMID- 21719028
TI  - Interacting mechanisms of impulsivity in bipolar disorder and antisocial
      personality disorder.
AB  - BACKGROUND: Bipolar disorder and antisocial personality disorder (ASPD) overlap
      in clinical characteristics and behavioral consequences. Impulsivity is prominent
      in both, but there is little information on how specific mechanisms of
      impulsivity differentiate, bridge, or underlie the disorders. METHODS: Subjects,
      all males, were controls (n = 46), bipolar disorder without cluster B personality
      disorder (n = 21), ASPD without bipolar disorder (n = 50), and bipolar disorder
      with ASPD (n = 16). Impulsivity measures were the Immediate Memory Task (IMT), a
      continuous performance test of response inhibition measuring ability to evaluate
      a stimulus before responding, and the Two-Choice Impulsivity Paradigm (TCIP), a
      choice between smaller-sooner and larger-later reward. Data were analyzed using
      general linear models analysis. RESULTS: Subjects with bipolar disorder had fewer
      IMT correct detections and slower reaction times than controls. Reaction times
      were faster with combined diagnoses than in bipolar disorder alone. TCIP
      responding in either diagnosis alone resembled controls, but was more impulsive
      in combined disorders. These differences persisted after correction for age and
      education, which had significant independent effects. In combined ASPD and
      bipolar disorder, increased reaction speed, impulsive response bias, and reward
      delay impulsivity occurred independent of substance-use disorder history.
      CONCLUSIONS: Impulsivity was increased in the combined disorders over either
      disorder alone. Results were consistent with at least partially distinct
      mechanisms of impulsivity in ASPD and bipolar disorder. Compensatory mechanisms
      for impulsivity in uncomplicated ASPD or bipolar disorder appear to be
      compromised or lost when the disorders are combined.

PMID- 21719029
TI  - Endovascular treatment of brain arteriovenous malformations ruptured during
      pregnancy--a report of two cases.
AB  - Acutely ruptured brain arteriovenous malformations (AVMs) are a known etiology of
      hemorrhagic stroke during pregnancy. The aim of this paper is to report two cases
      of patients which presented with ruptured AVMs during pregnancy and were
      successfully treated with endovascular techniques. Peculiar issues related to the
      application of this treatment strategy in this category of patients will be
      discussed as well. To the best of our knowledge, this therapeutic approach in
      cerebral AVMs ruptured during pregnancy has not been described yet.

PMID- 21719030
TI  - Migration of retained right ventricular epicardial pacing wire into the pulmonary
      artery: a rare complication after heart surgery.

PMID- 21719031
TI  - New innovative instruments facilitate both direct-vision and endoscopic-assisted
      mini-mitral valve surgery.
AB  - OBJECTIVE: The efficacy of new, innovative, original instruments, including a
      left atrial retractor, silicon annuloplasty ring sizer, modified Cosgrove aortic
      clamp, and reusable clip for fixing knots of polytetrafluoroethylene (Gore-Tex;
      WL Gore & Associates, Inc, Flagstaff, Ariz) suture, to allow surgical exposure in
      an ideal operative setting of mini-mitral valve repair surgery was verified.
      METHODS: Since 1998, a great deal of innovation has contributed to establishing
      mitral valve repair via right minithoracotomy as a routine surgical approach for
      mitral valve insufficiency in 252 cases. During the last 2 years, a newly
      launched left atrial retractor system attachable to the minithoracotomy spreader
      has been used. An additional retractor for the posterior wall of the left atrium
      was attached to the minithoracotomy spreader. The retractor moves flexibly and
      can be fixed in any favorable position to realize optimal exposure of the mitral
      valve. A 5 blade size was available depending on the left atrial size and target
      legion. By using the smallest size, even papillary muscles were exposed easily
      and clearly. Furthermore, a flexible silicon ring sizer, which could easily pass
      thorough a narrow working port without tissue damage, was used for sizing the
      annuloplasty ring. For the surgical technique, multiple chordal reconstructions
      by the loop technique with polytetrafluoroethylene (Gore-Tex CV-5 sutures) were
      applied. A reusable clip for fixing knots made it easy to tie the Gore-Tex suture
      in the correct position without slipping. RESULTS: No operative mortality
      occurred. There were 2 conversions to sternotomy for correction of aortic
      dissection (1) and for coronary artery bypass grafting (1). There were 2 early
      reoperations for failure of mitral valve repair. The mean aortic crossclamp time
      was 163.5 +/- 41.6 minutes. Annuloplasty with a ring or band was performed in all
      cases except one. The loop technique was used in 173 cases. Among them, a
      combination of the loop technique and resection and suture technique was used in
      56 cases. CONCLUSIONS: Newly innovated mini-mitral valve surgical instruments and
      techniques facilitate both direct-vision and endoscopic-assisted approaches and
      accomplish a favorable surgical outcome even in the complex pathology of mitral
      valve insufficiency.

PMID- 21719032
TI  - Outcomes of concomitant aortic valve replacement and coronary artery bypass
      grafting at teaching hospitals versus nonteaching hospitals.
AB  - OBJECTIVE: Hospitals with a high volume and academic status produce better
      patient outcomes than other hospitals after complex surgical procedures. Risk
      models show that concomitant aortic valve replacement and coronary artery bypass
      grafting pose a greater risk than isolated coronary artery bypass grafting or
      aortic valve replacement. We examined the relationship of hospital teaching
      status and the presence of a thoracic surgery residency program with aortic valve
      replacement/coronary artery bypass grafting outcomes. METHODS: By using the
      Nationwide Inpatient Sample database, we identified patients who underwent
      concomitant aortic valve replacement/coronary artery bypass grafting from 1998 to
      2007 at nonteaching hospitals, teaching hospitals without a thoracic surgery
      residency program, and teaching hospitals with a thoracic surgery residency
      program. Multivariate analysis was performed to identify intergroup differences.
      Risk-adjusted multivariable logistic regression analysis was used to assess
      independent predictors of in-hospital mortality and complication rates. RESULTS:
      The 3 groups of patients did not differ significantly in their baseline
      characteristics. Patients who underwent aortic valve replacement/coronary artery
      bypass grafting had higher overall risk-adjusted complication rates in
      nonteaching hospitals (odds ratio 1.58; 95% confidence interval, 1.39-1.80; P <
      .0001) and teaching hospitals without a thoracic surgery residency program (odds
      ratio 1.42; 95% confidence interval, 1.26-1.60; P < .0001) than in thoracic
      surgery residency program hospitals. However, no difference was observed in the
      adjusted mortality rate for nonteaching hospitals (odds ratio 0.95; 95%
      confidence interval, 0.87-1.04; P = .25) or teaching hospitals without a thoracic
      surgery residency program (odds ratio 1.00; 95% confidence interval, 0.92-1.08; P
      = .98) when compared with thoracic surgery residency program hospitals. Robust
      statistical models were used for analysis, with c-statistics of 0.98
      (complications) and 0.82 (mortality). CONCLUSION: Patients who require complex
      cardiac operations may have better outcomes when treated at teaching hospitals
      with a thoracic surgery residency program.

PMID- 21719033
TI  - Long-term results of pulmonary artery rehabilitation in patients with pulmonary
      atresia, ventricular septal defect, pulmonary artery hypoplasia, and major
      aortopulmonary collaterals.
AB  - OBJECTIVE: The study objective was to report the long-term results of pulmonary
      artery rehabilitation in patients with pulmonary atresia, ventricular septal
      defect, hypoplastic pulmonary arteries, and major aortopulmonary collaterals.
      METHODS: Since 1991, 20 patients with profound pulmonary artery hypoplasia (mean
      Nakata index 26 +/- 14 mm(2)/m(2)) have undergone a medico-surgical strategy of
      native pulmonary artery rehabilitation to achieve complete repair with
      satisfactory hemodynamics (right ventricle to aortic pressure ratio < 0.8).
      RESULTS: The first step, right ventricle to pulmonary artery connection, was
      performed at a median age of 4.1 (0.1-18.7) months with 1 operative death. After
      a median duration of 4.3 (1.1-26) months, the second step of interventional
      catheterizations followed (median, 2 (1-7)/patient), consisting of 36 pulmonary
      angioplasties, 11 stent implantations, and 20 collateral occlusions. Significant
      pulmonary artery growth was obtained in all cases with a Nakata index of 208 +/-
      85 mm(2)/m(2) before surgical correction (P < .001). The third step of surgical
      repair was performed at a median age of 1.9 (0.6-10.7) years, with right
      ventricular outflow reconstruction and ventricular septal defect closure
      fenestrated in 3 cases. During a mean follow-up of 8.2 +/- 4.5 years, pulmonary
      artery rehabilitation was pursued in most patients, with 47 pulmonary
      angioplasties, 15 stent implantations, and 11 collateral occlusions. Three
      patients with a poor hemodynamic result died. At last visit, the 16 survivors are
      in New York Heart Association class I (n = 12) or II (n = 4) with satisfactory
      hemodynamics in 13 cases. CONCLUSIONS: Pulmonary artery rehabilitation allows
      complete repair in the majority of patients with pulmonary atresia, ventricular
      septal defect, hypoplastic pulmonary arteries, and major aortopulmonary
      collaterals. However, long-term management often requires pursuit of the
      rehabilitation process.

PMID- 21719034
TI  - Right ventricular exclusion for a neonatal patient with Ebstein anomaly: a free
      wall resection of the right ventricle.

PMID- 21719035
TI  - Surgical problems and complex procedures: issues for operative time in robotic
      totally endoscopic coronary artery bypass grafting.
AB  - OBJECTIVE: Robotically assisted totally endoscopic coronary artery bypass
      grafting (TECAB) is a viable option for closed chest coronary surgery, but it
      requires learning curves and longer operative times. This study evaluated the
      effect of extended operation times on the outcome of patients undergoing TECAB.
      METHODS: From 2001 to 2009, 325 patients underwent TECAB with the da Vinci
      telemanipulation system. Correlations between operative times and preoperative,
      intraoperative, and early postoperative parameters were investigated. Receiver
      operating characteristic analysis was used to define the threshold of the
      procedure duration above which intensive care unit stay and ventilation time were
      prolonged. Demographic data, intraoperative and postoperative parameters, and
      survival data were compared. RESULTS: Patients with prolonged operative times
      more often underwent multivessel revascularization (P < .001) and beating-heart
      TECAB (P =.023). Other preoperative parameters were not associated with longer
      operative times. Incidences of technical difficulties and conversions (P < .001)
      were higher among patients with longer operative times. Prolonged intensive care
      unit stay, mechanical ventilation, hospital stay, and with requirement of blood
      products were associated with longer operative times. Receiver operating
      characteristic analysis showed operative times >445 minutes and >478 minutes to
      predict prolonged (>48 hours) intensive care unit stay and mechanical
      ventilation, respectively. Patients with procedures >478 minutes had longer
      hospital stays and higher perioperative morbidity and mortality. Kaplan-Meier
      analysis revealed decreased survival among patients with operative times >478
      minutes. CONCLUSIONS: Multivessel revascularization and conversions lead to
      prolonged operative times in totally endoscopic coronary artery bypass grafting.
      Longer operative times significantly influence early postoperative and midterm
      outcomes.

PMID- 21719036
TI  - Organic micropollutants in marine plastics debris from the open ocean and remote
      and urban beaches.
AB  - To understand the spatial variation in concentrations and compositions of organic
      micropollutants in marine plastic debris and their sources, we analyzed plastic
      fragments (~10 mm) from the open ocean and from remote and urban beaches.
      Polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs),
      dichloro-diphenyl-trichloroethane and its metabolites (DDTs), polybrominated
      diphenyl ethers (PBDEs), alkylphenols and bisphenol A were detected in the
      fragments at concentrations from 1 to 10,000 ng/g. Concentrations showed large
      piece-to-piece variability. Hydrophobic organic compounds such as PCBs and PAHs
      were sorbed from seawater to the plastic fragments. PCBs are most probably
      derived from legacy pollution. PAHs showed a petrogenic signature, suggesting the
      sorption of PAHs from oil slicks. Nonylphenol, bisphenol A, and PBDEs came mainly
      from additives and were detected at high concentrations in some fragments both
      from remote and urban beaches and the open ocean.

PMID- 21719037
TI  - Accumulation of heavy metals to assess the health status of swordfish in a
      comparative analysis of Mediterranean and Atlantic areas.
AB  - During the last few decades, the combined effects of natural and human activities
      acting on the Mediterranean Sea basin have caused a reduction in the swordfish
      (Xiphias gladius, L. 1758) population. In this project, we investigated the
      accumulation of lead (Pb), cadmium (Cd) and mercury (Hg) levels in the Atlantic
      and Mediterranean populations of swordfish during a five-year survey. In the
      marine environment, top predators such as swordfish accumulate high
      concentrations of toxic metals, and thus, potentially incur a high toxicological
      risk. Furthermore, heavy metals, such as chemical pollutants, have strong long
      term effects on fish, and thus, constitute a high risk for the resource and
      humans that consume it. The aim of this work is to contribute to the assessment
      of the state of European swordfish population health. We analyzed muscle tissue
      from 56 specimens captured in Mediterranean and Atlantic areas for trace
      elements. Mean concentrations of Hg, Cd, and Pb were in the following ranges:
      0.66-2.41, 0.04-0.16, and 0.97-1.36 mg/kg ww, respectively. These data suggest a
      need for continuous monitoring to avoid reductions in the population of this fish
      species of high commercial and ecological interest.

PMID- 21719038
TI  - Recovery of macrobenthos in defaunated tropical estuarine sediments.
AB  - In the estuarine environment, hypoxia and/or anoxia have become a major cause of
      benthic defaunation and are strongly associated with increased eutrophication.
      Mesoscale field experiments were carried out to examine the recolonization and
      recovery time of macrobenthos after defaunation. Azoic sediments were achieved by
      covering four areas with polyethylene sheeting. Temporal changes and depth
      distribution of macrobenthos within the defaunated sediments were compared with
      those in undisturbed natural sediments at the same site. Within 3 days, annelids
      appeared as the first immigrants. After 153 days, the process of recovery had not
      yet been completed in terms of species richness. Whereas diversity and evenness
      showed no significant differences between treatments during the entire
      experiment, multivariate analyses proved that differences between treatments were
      still significant 93 days after the start of the experiment.

PMID- 21719039
TI  - A quantification of the standing stock of macro-debris in Majuro lagoon and its
      effect on hard coral communities.
AB  - The accumulation of debris is an insidious problem throughout the world's oceans.
      Here we document 234.24 items of macro-debris/km2 in the shallow populated parts
      of Majuro lagoon (Republic of the Marshall Islands) which is the second highest
      standing stock of macro-debris recorded to date in any benthic marine habitat in
      the world. The majority of macro-debris was from household sources (78.7%) with
      the peak abundance recorded in areas of medium affluence. Marine debris causes
      suffocation, shading, tissue abrasion and mortality of corals and we show a
      significant negative correlation exists between the level of hard coral cover and
      coverage of marine debris. Given long decomposition times, even if the input of
      rubbish to Majuro lagoon is stopped immediately, the standing stock of debris
      will persist for centuries. Multiple new initiatives are needed to curtail the
      direct and indirect dumping of waste in Majuro lagoon.

PMID- 21719040
TI  - Polybrominated diphenyl ethers (PBDEs) in marine foodstuffs in Australia: residue
      levels and contamination status of PBDEs.
AB  - Edible marine products (n=24) collected from the fish markets in Adelaide,
      Australia, were analysed for the presence of polybrominated diphenyl ethers
      (PBDEs). The total concentration of 11 PBDE congeners found in the marine
      products ranged from 1.01 to 45 ng/g fresh weight. Among the samples analysed,
      imported silver fish and prawns from Vietnam and Thailand respectively, recorded
      the highest ?PBDEs concentrations (45.10 and 43.29 ng/g fresh weight) as against
      13.08 and 12.57 ng/g fresh weight in Australian king prawns and Gar fish. BDE-209
      was the most dominant congener in the marine products followed by BDE-47, 99 and
      100. The calculated average daily intakes of ?PBDEs per day for an adult male and
      female (19 or more years old) were 1026.8 and 1188.4 ng/kg per day, respectively.
      This study clearly shows that the dietary exposure to marine foods can contribute
      to PBDEs accumulation in human body.

PMID- 21719042
TI  - [Tuberculous spondylitis (Pott's disease)].

PMID- 21719041
TI  - [Prevalence of target organ damage and metabolic abnormalities in resistant
      hypertension].
AB  - BACKGROUND AND OBJECTIVE: Patients with resistant hypertension (RH) are
      relatively frequently visited in specialized units of hypertension. The aim of
      this study was to assess the prevalence of target organ damage, central obesity
      and metabolic syndrome in a cohort of patients with RH consecutively included in
      the Register of Resistant Hypertension of the Spanish Society of Hypertension
      (SHE-LELHA). PATIENTS AND METHODS: Cross-sectional, multicenter epidemiologic
      study in usual clinical practice conditions. Patients with clinical diagnosis of
      resistant hypertension, that is, office systolic and diastolic blood pressure >=
      140 mm Hg and/or >= 90 mm Hg, respectively, despite a prescribed therapeutic
      schedule with an appropriate combination of three or more full-dose
      antihypertensive drugs, including a diuretic, were consecutively recruited from
      specialized hypertension units spread through Spain. Demographic and
      anthropometric characteristics as well as cardiovascular risk factors and
      associated conditions were recorded, and all the subjects underwent 24-h
      ambulatory blood pressure monitoring. Left ventricular hypertrophy was considered
      as a left ventricular mass index >= 125 g/m(2) in males and >= 110 g/m(2) in
      females. Left atrial enlargement was defined as an indexed left atrium diameter
      >= 26 mm/m(2). Microalbuminuria was defined as a urinary albumin/creatinine ratio
      >= 22 mg/g in males and >= 31 mg/g in females. RESULTS: 513 patients were
      included, aged 64+/-11 years old, 47% women. Central obesity was present in 65.7%
      (CI 95% 61.6-69.9), 38.6% (CI 95% 34.4-42.8) had diabetes and 63.7% (CI 95% 59.4
      67.9) had metabolic syndrome. The prevalence of left ventricular hypertrophy and
      left atrial enlargement, determined by echocardiography was 57.1% (CI 95% 50.8
      63.5) and 10.0% (CI 95% 6.3-13.7) respectively. Microalbuminuria was found in
      46.6% (CI 95% 41.4-51.8) of the subjects. Patients with metabolic syndrome were
      significantly older (65.4+/-11 and 62.5+/-12 years; P=.0052), presented a higher
      prevalence of diabetes (52.0% vs. 16.6; P<.0001) and were treated more frequently
      with >= 4 antihypertensive drugs (65.1 vs. 50.0%, P=.011). CONCLUSION: The
      prevalence of central obesity, metabolic syndrome and target organ damage is very
      high in resistant hypertensive subjects.

PMID- 21719043
TI  - Evaluation of liver fibrosis by transient elastography in methotrexate treated
      patients.
AB  - BACKGROUND AND AIMS: Methotrexate (MTX) safety is questioned by the risk of
      inducing liver fibrosis (LF). As transient elastography (FibroScan(r)) is an
      effective non-invasive technique to evaluate LF, our aims were to assess LF in
      MTX-treated patients, to evaluate LF regarding treatment duration and cumulative
      dose, and to determine differences depending on the underlying disease. PATIENTS
      AND METHODS: Prospective study including patients with rheumatoid arthritis,
      inflammatory bowel disease, and psoriasis treated with MTX. Hepatic stiffness was
      determined by FibroScan(r). The LF cut-off values were established using METAVIR
      score. RESULTS: Of 53 patients, 22 were men (41.5%), mean age was 55 (15) years,
      17 (32%) had rheumatoid arthritis, 18 (34%) inflammatory bowel disease, and 18
      (34%) psoriasis. Mean MTX cumulative dose was 1,805 (1,560) mg, and mean
      treatment duration was 178 weeks. Mean hepatic stiffness was 6.19 (2.43) KPa. In
      49 patients (92.5%), absence/mild LF was found (F <= 2), and 4 patients (7.5%)
      had advanced LF (F >= 3). Treatment duration or cumulative doses of MTX were not
      associated with LF. CONCLUSIONS: Regarding LF development, MTX therapy is safe.
      FibroScan(r) is useful for monitoring LF in MTX-treated patients.

PMID- 21719044
TI  - [Resistant hypertension: beyond a bad control of blood pressure].

PMID- 21719045
TI  - [Is it necessary to change the regulation in which drugs are not the objective of
      the medical research?].

PMID- 21719046
TI  - [Descriptive analysis of diseases associated with Streptococcus bovis
      bacteremia].
AB  - BACKGROUND AND OBJECTIVE: It is well-known the relationship between Streptococcus
      bovis (S. bovis) bacteremia and colon cancer, liver cirrhosis and others
      neoplasms. However, a study protocol to rule out these underlying diseases has
      not been carried out yet. Our objective was to describe S. bovis bacteremia and
      associated diseases. PATIENTS AND METHOD: Multicenter, retrospective cohort
      study. S. bovis bacteremias episodes between 2001 and 2009 were included. Mean
      variables: colon neoplasm, non-colonic neoplasm or liver cirrhosis.
      Epidemiologist aspects, bacteremia related variables, personal and familiar
      history and clinical and analytical data were collected. RESULTS: Ninety three
      patients were included. One out of four individuals had a colon neoplasm. Fifty
      seven per cent were concomitant cases with bacteremia and six cases were
      diagnosed after bacteremia (time bacteremia-diagnosis of neoplasm [months],
      median [Q1-Q3], 2.6 [1-11]). Fourteen (15%) patients were diagnosed with any non
      colonic neoplasm (mainly biliary and pancreatic [6 cases] or esophagus-gastric [3
      cases]). There were three patients (21%) with concomitant bacteremia non-colonic
      neoplasm and two after it (1.2 and 10.4 months). Twenty-one (23%) patients
      suffered from liver cirrhosis. CONCLUSIONS: Patients with S. bovis bacteremia
      must undergo a study designed to rule out underlying diseases. We suggest that
      this study should include: a colonic evaluation, ideally by colonoscopy, a liver
      evaluation by serum chemistry, an abdominal ultrasound scan or a method of liver
      fibrosis assessment, a gastroscopy and an evaluation of biliary and pancreatic
      areas by magnetic resonance imaging.

PMID- 21719047
TI  - [Diagnostic approach to Streptococcus bovis bacteremia, or the limits of the
      evidence-based medicine].

PMID- 21719048
TI  - [Renal-cell carcinoma and multiple mieloma: synchronic association with posible
      immunologic pathogenesis].

PMID- 21719049
TI  - [Quantification of hepatitis B virus HBsAg: clinical implications].
AB  - The surface antigen of hepatitis B virus (HBsAg) is the main serological marker
      of HBV infection since its discovery almost 50 years ago. Currently the
      quantification of HBsAg has acquired special relevance as there are commercial
      tests to measure its levels. Several studies have shown that in patients treated
      with pegylated interferon alfa the fall of HBsAg levels predicts the loss of
      HBsAg and persistent virologic response. The role of the quantification of HBsAg
      in the treatment with nucleoside analogues is still not well understood and
      requires further studies.

PMID- 21719050
TI  - [Body packer].

PMID- 21719051
TI  - [Paradox of obesity in heart failure: results from the Spanish RICA Registry].
AB  - BACKGROUND AND OBJECTIVES: Obesity is a risk factor for heart failure (HF).
      Paradoxically, it has been described that body mass index (BMI) is inversely
      associated with mortality. The aim of this study was to analyse the relationship
      between BMI and mortality in a cohort of patients with HF. PATIENTS AND METHODS:
      All patients included in the RICA Registry between March 2008 and September 2009
      were analysed. RICA is a multicenter, prospective cohort study that includes
      patients admitted for decompensated HF in Spanish Internal Medicine Services.
      Patients were divided according to the WHO body weight categories. RESULTS: 712
      patients were included; 54% were women and mean age was 77.3 years. Hypertensive
      cardiopathy was the most common etiology of HF with some differences according to
      BMI categories, being valvular disease more frequent among obese and overweight
      patients and ischemic HF among normal weight patients. Mean left ventricle
      ejection fraction was 50.2% and it was higher among higher BMI categories.
      Natriuretic peptide levels were significantly lower among higher BMI categories
      (P<.05). Overall mortality after one-year of follow-up was 13.9% and it was
      significantly lower among higher BMI categories: normal BMI 20.4%, overweight
      14.7% and obesity 8.5% (P<.01). In the multivariate analysis, overweight was
      significantly and independently associated with an increased mortality risk in
      comparison with obesity: RR 3.05 (IC95% 1.24-7.54). CONCLUSIONS: An increase in
      BMI was associated with lower levels of natriuretic peptides and lower mortality.

PMID- 21719052
TI  - Toussaintines A-E: antimicrobial indolidinoids, a cinnamoylhydrobenzofuranoid and
      a cinnamoylcyclohexenoid from Toussaintia orientalis leaves.
AB  - Toussaintine A (N-cinnamoyl-5,6-dehydro-4-hydroxyindolidin-2,7-dione),
      toussaintine B (N-cinnamoyl-5,6-dehydro-4,7-dihydroxyindolidin-2-one),
      toussaintine C (N-cinnamoyl-5,6-dehydro-4-hydroxyindolidin-7-one), toussaintine D
      (N-cinnamoyl-2-amino-4-hydroxy-7-oxo-2,3,8,9-tetrahydrobenzofuran) and
      toussaintine E (N-cinnamoyl-1-acetoxymethyl-2-amino-1-hydroxycyclox-5-en-4-one)
      were isolated as antibacterial and antifungal constituents of the leaves of
      Toussaintia orientalis Verdc. (Annonaceae) and their structures established from
      analysis of spectroscopic data. The compounds belong to a series of variously
      cyclized aminocinnamoyl tetraketide derivatives, showing the importance of rarely
      occurring Annonaceae species as sources of structurally diverse natural products.

PMID- 21719053
TI  - Lateral approach for laparoscopic splenic vessel-preserving distal
      pancreatectomy.
AB  - AIM: We sought to evaluate the feasibility of the lateral approach for
      laparoscopic splenic vessel-preserving distal pancreatectomy (LA-SVPDP).
      BACKGROUND: Complete preservation of the splenic vessels is an ideal outcome in
      spleen-preserving distal pancreatectomy (SPDP). However, the preservation of the
      vessels is challenging in laparoscopic surgery because the splenic vein is often
      embedded in the pancreatic parenchyma. Herein we have described LA-SVPDP, the
      most feasible method for laparoscopic SPDP, and the outcome of our initial
      experience. PATIENTS: Twenty-three patients underwent laparoscopic SPDP. Before
      we adopted LA-SVPDP, 8 patients underwent the Warshaw method and 6 underwent
      SVPDP. After the adoption of LA-SVPDP, 8 patients underwent LA-SVPDP and 1 donor
      underwent the Warshaw method. RESULTS: None of patients undergoing LA-SVPDP
      required conversion to an open operation, whereas 2 patients undergoing the other
      procedures were converted to open operations. Five out of 8 patients who
      underwent the Warshaw method showed engorgement of the gastric veins, revealed by
      computed tomography. However, only 1 of the 5 patients showed mild gastric
      varices on endoscopy. CONCLUSION: Although the Warshaw method is acceptable with
      a low incidence of gastric varices in our analysis, SVPDP is a feasible approach
      for SPDP. Our LA-SVPDP technique may contribute to safer and easier SVPDP in
      laparoscopic surgery.

PMID- 21719054
TI  - Integrin-linked kinase regulates phosphatase and tensin homologue activity to
      promote tumorigenesis in neuroblastoma cells.
AB  - BACKGROUND: The phosphatidylinositol 3-kinase (PI3K), a critical intracellular
      pathway, is negatively regulated by phosphatase and tensin homologue (PTEN).
      Integrin-linked kinase (ILK) induces phosphorylation of Akt leading to an
      increase in cell survival. However, a potential interaction between ILK and PTEN
      activity in neuroblastoma cells is unknown. We sought to examine the relationship
      between ILK and PTEN in the PI3K/Akt signaling pathway in neuroblastoma
      tumorigenesis. METHODS: The human neuroblastoma cell line, BE(2)-C, was
      transfected with small interfering or short hairpin RNA to silence ILK
      expression. A plasmid containing the ILK wild-type (ILK wt) gene was transfected
      to overexpress ILK. Cell proliferation was assessed, and anchorage independence
      was measured by soft agar assay. Insulin-like growth factor-1 was used to
      stimulate the PI3K/Akt pathway. Protein levels were determined by Western
      blotting. RESULTS: Transient silencing of ILK produced correlative decreases in
      PTEN expression, cell proliferation, and soft agar colony formation. Conversely,
      stably transfected ILK knockdown cells showed an increase in phospho-Akt levels,
      leading to cell proliferation. CONCLUSION: ILK plays an important role in the
      regulation of PI3K/Akt pathway via PTEN or an upstream effector of PTEN. The
      effects of ILK silencing on PTEN expression seem to be critically dependent on
      duration of ILK dysregulation.

PMID- 21719055
TI  - Controlled release of vascular endothelial growth factor enhances intestinal
      adaptation in rats with extensive small intestinal resection.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) has been shown to be an
      essential factor in the intestinal adaption after extensive bowel resection. The
      present study investigates the controlled release of VEGF as a way to improve
      intestinal adaptation. MATERIALS AND METHODS: Biodegradable microspheres with or
      without VEGF were made using a double emulsion technique. Approximately 80% of
      the small intestine was removed, leaving the entire duodenum, 10 cm of jejunum,
      and 7 cm of ileum. The microspheres were distributed on the anastomosed small
      bowel. The animals were sacrificed after 14 days, and the adapted jejunum and
      ileum were analyzed for sucrase activity and histologic parameters. RESULTS: The
      average villus lengths of the adapted jejunum and ileum were 680 and 350 MUm in
      rats that received blank microspheres, compared to 810 and 720 MUm in rats that
      received VEGF microspheres. The average sucrase activity of the adapted jejunum
      and ileum was 0.0202 and 0.0073 MUmol/mg protein/min in rats that received blank
      microspheres, compared with 0.0236 and 0.0232 MUmmol/mg protein/min in rats that
      received VEGF microspheres. CONCLUSION: The data suggest that the controlled
      delivery of VEGF from microspheres enhances the adaptation of the small intestine
      in rats. The controlled delivery of VEGF over time can potentially be used in
      patients following extensive intestinal resection.

PMID- 21719056
TI  - Outcomes of plastic closure in gastroschisis.
AB  - BACKGROUND: Gastroschisis is a congenital abdominal wall defect in which the
      intestines develop outside the abdomen and are exposed to amniotic fluid. When
      the defect is small, lymphatic, venous, and intestinal obstruction may occur and
      contribute to the formation of intestinal edema, atresia, ischemia, and a thick
      inflammatory peel. Treatment requires early coverage of abdominal contents either
      by primary closure or by the placement of temporary Silastic silo followed by
      abdominal wall closure. Currently, both traditional suture closure and the
      sutureless plastic closure are being employed to repair the gastroschisis defect.
      The goal of the current study is to evaluate plastic closure. We predict no
      difference will be found in clinical outcomes between plastic closure and
      traditional suture closure. METHODS: A retrospective review of 80 patients
      treated between 2000 and 2009 was performed. Plastic closure was used in 52 (65%)
      and traditional suture closure in 28 (35%) babies. The surgical procedure was
      determined by surgeon preference. Of the 31(39%) babies who required silos, 15
      (19%) were treated with plastic closure and 16 (20%) underwent traditional
      closure. We collected the following demographic data and clinical progression
      data. Using SAS 9.2 (SAS Institute Inc, Cary, NC), we conducted linear
      regression, logistic regression, and time to event models to compare the
      following outcomes: days on ventilator, days to start enteral feeds, days to
      reach goal enteral feeds, days on total parenteral nutrition, hospital charges,
      duration of stay, mortality, and complications. RESULTS: The mean duration of
      follow-up was 11.4 months. Patients spent an average of 6 days on the ventilator.
      There were 2 mortalities. A multivariate analysis demonstrated that no
      differences were found between the 2 closures with most of the outcomes; however,
      when compared with traditional suture closure, those babies treated with plastic
      closure spent 4 days fewer days on the ventilator (P < .01). Those babies who
      underwent suture closure were more likely to have an infection or sepsis (odds
      ratio, 5.15; P < .001). When the entire cohort was considered, no significant
      difference was found between plastic and suture closure in time to start feeds,
      time to reach goal feeds, time on parenteral nutrition, hospital charges,
      duration of stay, or complications. Ventral hernias were noted in 46 (58%)
      patients, 32 (62%) after plastic closure and 14 (50%) after suture closure (P =
      .32). Hernia repair was required in 16 (20%) patients, 11 (21%) after plastic
      closure, and 5 (18%) after traditional repair (P = .32). In the silo cohort,
      children treated with plastic closure required 7.5(P < .01) fewer days to start
      enteral feeds than those treated with suture closure. CONCLUSION: Plastic closure
      of abdominal wall defects in gastroschisis is effective both as a primary
      procedure and after silo placement. A multivariate analysis shows plastic closure
      to be associated with fewer days of mechanical ventilation and less likelihood of
      developing infection or sepsis.

PMID- 21719057
TI  - Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3
      pathway.
AB  - BACKGROUND: Cardiac surgery induces the release of inflammatory mediators that
      can prolong cardiac dysfunction after operative intervention. Interleukin-10 (IL
      10), a potent inhibitor of myocardial inflammation, is a known factor in
      myocardial protection after ischemia/reperfusion (I/R) injury. We hypothesized
      that IL-10 activity during initial reperfusion is mediated through the signal
      transducer and activator of transcription 3 (STAT3) pathway. METHODS: Adult rat
      hearts were isolated and perfused via Langendorff protocol and subjected to
      global I/R. After determining the effective IL-10 dose, hearts were administered
      vehicle, IL-10, or IL-10 + Stattic (specific STAT3 inhibitor) 1 min prior to
      ischemia. After reperfusion, hearts were sectioned and assessed for levels of
      myocardial inflammatory cytokines and protein. RESULTS: The IL-10 minimum
      effective dose was 1 MUg. IL-10-treated hearts had improved markedly myocardial
      function after global I/R compared to both vehicle and IL-10 + Stattic groups. In
      addition, IL-10 treatment was associated with a significant decrease in
      myocardial interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) and increase in
      myocardial IL-10. Myocardial STAT3 was elevated markedly in IL-10 treated hearts.
      CONCLUSION: IL-10 improves myocardial function after acute global I/R and
      suppresses inflammation through the STAT3 pathway. The administration of anti
      inflammatory agents may have potential therapeutic applications in cardiac
      surgery.

PMID- 21719058
TI  - Examining the myth of the "July Phenomenon" in surgical patients.
AB  - BACKGROUND: The objective of this study is to evaluate morbidity and mortality
      rates in surgical patients at the beginning of the academic year. METHODS: The
      National Surgical Quality Improvement Program database was utilized to gather
      data on the 10 most common inpatient operative procedures from 2005-2007. Study
      end points included mortality, serious adverse events (SAE), and all morbidities.
      Statistical analysis of outcomes was conducted examining the total population,
      and then stratified by operation to assess for significant differences in end
      points (P < .05). RESULTS: A total of 89,473 patients were identified. During the
      first academic quarter, the mortality rate was no different in the study group
      than the control group (2.0% vs 2.2%, P = .793). Overall SAE and morbidity rates
      were similar between populations (11.5% vs 11.4%, P = .697 and 18.3% vs 17.8%, P
      = .076, respectively). When stratified by operation, "artery bypass graft" (3.7%
      vs 2.9%, P = .039) and "repair bowel opening" (1.1% vs 0.6%, P = .033) subsets
      had increases in mortality rate. Multivariate analysis confirmed the deleterious
      effect of first quarter admission in only the "artery bypass graft" subset (OR =
      1.35, CI 1 = .023-1.774). CONCLUSION: By in large, these data refute the "July
      Phenomenon." Multivariate analysis revealed patient disease to have a greater
      impact than timing of operation in the "repair bowel opening" subset. The "artery
      bypass graft" population was affected by timing of operation and the very small
      effect on mortality (<1%) may reflect new surgery residents being unfamiliar with
      the management of complex cardiovascular disease.

PMID- 21719059
TI  - Tumor-specific expression and alternative splicing of the COL6A3 gene in
      pancreatic cancer.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease; a
      prominent desmoplastic reaction is a defining characteristic. Fibrillar
      collagens, such as collagen I and to a lesser extent, collagens III and V,
      comprise the majority of this stromal fibrosis. Type VI collagen (COL6) forms a
      microfibrillar network associated with type I collagen fibrils. The expression of
      COL6 has been linked with inflammation and survival. Importantly, tumor-specific
      alternative splicing in COL6A3 has been identified in several cancers by genome
      exon arrays. We evaluated the expression and localization of COL6A3 in PDA and
      premalignant lesions and explored the presence of alternative splicing events.
      METHODS: We analyzed paired PDA-normal (n = 18), intraductal papillary mucinous
      neoplasms (IPMN; n = 5), pancreatic cystadenoma (n = 5), and 8 PDA cell lines
      with reverse transcriptase polymerase chain reaction, using unique primers that
      identify total COL6A3 gene and alternative splicing sites in several of its
      exons. Western blot analysis and immunohistochemistry were used to analyze the
      expression levels and localization of COL6A3 protein in the different lesions,
      and in 2 animal models of PDA. RESULTS: COL6A3 protein levels were significantly
      upregulated in 77% of the paired PDA-adjacent tissue examined. COL6A3 was mainly
      present in the desmoplastic stroma of PDA, with high deposition around the
      malignant ducts and in between the sites of stromal fatty infiltration. Analysis
      of the COL6A3 splice variants showed tumor-specific consistent inclusion of exons
      3 and 6 in 17 of the 18 (94%) paired PDA-adjacent tissues. Inclusion of exon 4
      was exclusively tumor specific, with barely detectable expression in the adjacent
      tissues. IPMN and pancreatic cystadenomas showed no expression of any of the
      examined exons. Total COL6A3 mRNA and exon 6 were identified in 6 PDA cell lines,
      but only 2 cell lines (MIA PACA-2 and ASPC-1) expressed exons 3 and 4. In both
      the xenograft and transgenic models of PDA, COL6A3 immunoreactivity was present
      in the stroma and some PDA cells. CONCLUSION: We have described, for the first
      time, a dynamic process of tumor-specific alternative splicing in several exons
      of stromal COL6A3. Alternatively spliced proteins may contribute to the etiology
      or progression of cancer and may serve as markers for cancer diagnosis.
      Identification of COL6A3 isoforms as PDA-specific provides the basis for future
      studies to explore the oncogenic and diagnostic potential of these alternative
      splicing events.

PMID- 21719060
TI  - Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal
      adaptation in a mouse model of short bowel syndrome.
AB  - BACKGROUND: Glucagon-like peptide-2 induces small intestine mucosal epithelial
      cell proliferation and may have benefit for patients who suffer from short bowel
      syndrome. However, glucagon-like peptide-2 is inactivated rapidly in vivo by
      dipeptidyl peptidase IV. Therefore, we hypothesized that selectively inhibiting
      dipeptidyl peptidase IV would prolong the circulating life of glucagon-like
      peptide-2 and lead to increased intestinal adaptation after development of short
      bowel syndrome. METHODS: Eight-week old C57BL/6J mice underwent a 50% proximal
      small bowel resection and were treated with either sitagliptin, a dipeptidyl
      peptidase IV-inhibitor, starting 1 day before surgery versus placebo. The
      efficacy of dipeptidyl peptidase IV-inhibitor was assessed 3 days after
      resection, including intestinal morphology, epithelial cell apoptosis, and
      epithelial cell proliferation. Adaptive mechanisms were assessed with
      quantitative real-time polymerase chain reaction, and plasma bioactive glucagon
      like peptide-2 was measured by radioimmunoassay. RESULTS: Body weight loss and
      peripheral blood glucose levels did not change compared with short bowel syndrome
      controls. Dipeptidyl peptidase IV-inhibitor treatment led to significant
      increases in villus height and crypt depth. Dipeptidyl peptidase IV-inhibitor
      treatment did not change EC apoptosis rates significantly, but it did increase
      crypt epithelial cell proliferation significantly versus placebo-short bowel
      syndrome controls. Dipeptidyl peptidase IV-inhibitor treatment markedly increased
      messenger RNA expression of beta-catenin and c-myc in ileal mucosa. Plasma
      glucagon-like peptide-2 levels increased significantly (~ 40.9%) in dipeptidyl
      peptidase IV-inhibitor short bowel syndrome mice. CONCLUSION: Dipeptidyl
      peptidase IV-inhibitor treatment increased short bowel syndrome adaptation and
      might potentially be useful for short bowel syndrome patients.

PMID- 21719061
TI  - The influence of donor age on liver regeneration and hepatic progenitor cell
      populations.
AB  - BACKGROUND: Recent reports suggest that donor age might have a major impact on
      recipient outcome in adult living donor liver transplantation (LDLT), but the
      reasons underlying this effect remain unclear. The aims of this study were to
      compare liver regeneration between young and aged living donors and to evaluate
      the number of Thy-1+ cells, which have been reported to be human hepatic
      progenitor cells. METHODS: LDLT donors were divided into 2 groups (Group O, donor
      age >= 50 years, n = 6 and Group Y, donor age <= 30 years, n = 9). The remnant
      liver regeneration rates were calculated on the basis of computed tomography
      volumetry on postoperative days 7 and 30. Liver tissue samples were obtained from
      donors undergoing routine liver biopsy or patients undergoing partial hepatectomy
      for metastatic liver tumors. Thy-1+ cells were isolated and counted using
      immunomagnetic activated cell sorting (MACS) technique. RESULTS: Donor liver
      regeneration rates were significantly higher in young donors compared to old
      donors (P = .042) on postoperative day 7. Regeneration rates were significantly
      higher after right lobe resection compared to rates after left lobe resection.
      The MACS findings showed that the number of Thy-1+ cells in the human liver
      consistently tended to decline with age. CONCLUSION: Our study revealed that
      liver regeneration is impaired with age after donor hepatectomy, especially after
      right lobe resection. The declining hepatic progenitor cell population might be
      one of the reasons for impaired liver regeneration in aged donors.

PMID- 21719062
TI  - Estrogen-induced SDF-1 production is mediated by estrogen receptor-alpha in
      female hearts after acute ischemia and reperfusion.
AB  - BACKGROUND: Gender differences exist in myocardial response to acute
      ischemia/reperfusion (I/R) injury and estrogen mediates cardioprotection in the
      female heart after I/R. Accumulating evidence has indicated that stromal cell
      derived factor-1 (SDF-1) is increased in the ischemic heart and initiates
      cardioprotective effects. However, it is unknown whether SDF-1 plays a role in
      gender-specific response to myocardial I/R and in estrogen-induced acute
      protection. Therefore, we hypothesize that (1) increased SDF-1 production will be
      observed in female hearts compared with male hearts in response to I/R, which is
      attributable to the effect of estrogen; and that (2) estrogen receptor (ER)alpha,
      not ERbeta mediates estrogen-contributed SDF-1 expression in female hearts after
      I/R. METHODS: Heart tissue subjected to I/R injury was assessed for myocardial
      expression of SDF-1 (by enzyme-linked immunosorbent assay) and SDF-1 receptor
      CXCR4 (Western blot). Groups were as follows: Rat hearts from adult male, female,
      ovariectomized female (OVX F), and male and OVX F supplemented with chronic
      17beta-estradiol (E2), and mouse hearts from adult male and female wild-type,
      ERalpha knockout (ERalphaKO) and ERbetaKO. RESULTS: I/R significantly increased
      myocardial SDF-1 expression in both genders. Higher levels of SDF-1 existed in
      female hearts after I/R compared with males. Depletion of endogenous estrogen by
      ovariectomy reduced cardiac SDF-1 production in females after I/R. E2
      supplementation significantly restored SDF-1 expression in OVX F and males
      compared with their counterparts. Notably, ablation of ERalpha, not ERbeta,
      markedly decreased SDF-1 production in females after I/R. Unlike SDF-1, cardiac
      CXCR4 expression was not affected by gender, sex hormone, or ERs in the ischemic
      heart. CONCLUSION: Our study represents the first evidence that female hearts
      exhibit higher levels of SDF-1 expression compared with males after acute I/R.
      This increased myocardial SDF-1 production in females is partly owing to effect
      of estrogen through ERalpha, but not ERbeta.

PMID- 21719063
TI  - Twenty-year experience with surgical management of recto-urinary fistulas by
      posterior sagittal transrectal approach (York-Mason).
AB  - BACKGROUND: We describe our 20-year experience with a posterior transrectal
      approach (York-Mason procedure) to treat recto-urinary fistula (RUF). Most RUFs
      are secondary to lower urinary or intestinal tract surgery. Spontaneous closure
      is infrequent, and operative treatment is often mandatory. Several surgical
      approaches have been proposed. METHODS: We reviewed retrospectively the medical
      records of 14 patients presenting with RUF in our Department between 1988 and
      2010. In 10 patients, RUFs developed after radical retropubic prostatectomy
      (RRP); in the other 4 patients, RUFs resulted after other surgical interventions.
      All patients were treated with the York-Mason approach. A temporary colostomy and
      suprapubic cystostomy were performed in all patients except one. RESULTS: All
      patients were treated successfully. After fistulectomy, colostomies were closed
      after 4 mo, and patients reported fecal continence and no postoperative anal
      strictures. The colostomy was left in place permanently in 1 patient due to the
      simultaneous presence of Crohn's disease, in another with ulcerative
      rectocolitis, and in a third scheduled for adjuvant radiotherapy for relapse
      after RRP. In 1 patient, daily medications were essential because of wound
      infection. In the patient with Crohn's disease, the fistula recurred 11 years
      after first repair. Two patients died of metastatic prostate cancer 1 year after
      repair of the RUF. CONCLUSION: The posterior sagittal transrectal approach allows
      easy access and good surgical exposure, facilitating identification of the
      fistulous tract. In our opinion, the York-Mason approach guarantees the greatest
      success rate with the least morbidity.

PMID- 21719064
TI  - Study on the bubble transport mechanism in an acoustic standing wave field.
AB  - The use of bubbles in applications such as surface chemistry, drug delivery, and
      ultrasonic cleaning etc. has been enormously popular in the past two decades. It
      has been recognized that acoustically-driven bubbles can be used to disturb the
      flow field near a boundary in order to accelerate physical or chemical reactions
      on the surface. The interactions between bubbles and a surface have been studied
      experimentally and analytically. However, most of the investigations focused on
      violently oscillating bubbles (also known as cavitation bubble), less attention
      has been given to understand the interactions between moderately oscillating
      bubbles and a boundary. Moreover, cavitation bubbles were normally generated in
      situ by a high intensity laser beam, little experimental work has been carried
      out to study the translational trajectory of a moderately oscillating bubble in
      an acoustic field and subsequent interactions with the surface. This paper
      describes the design of an ultrasonic test cell and explores the mechanism of
      bubble manipulation within the test cell. The test cell consists of a transducer,
      a liquid medium and a glass backing plate. The acoustic field within the multi
      layered stack was designed in such a way that it was effectively one dimensional.
      This was then successfully simulated by a one dimensional network model. The
      model can accurately predict the impedance of the test cell as well as the mode
      shape (distribution of particle velocity and stress/pressure field) within the
      whole assembly. The mode shape of the stack was designed so that bubbles can be
      pushed from their injection point onto a backing glass plate. Bubble radial
      oscillation was simulated by a modified Keller-Miksis equation and bubble
      translational motion was derived from an equation obtained by applying Newton's
      second law to a bubble in a liquid medium. Results indicated that the bubble
      trajectory depends on the acoustic pressure amplitude and initial bubble size: an
      increase of pressure amplitude or a decrease of bubble size forces bubbles larger
      than their resonant size to arrive at the target plate at lower heights, while
      the trajectories of smaller bubbles are less influenced by these factors. The
      test cell is also suitable for testing the effects of drag force on the bubble
      motion and for studying the bubble behavior near a surface.

PMID- 21719065
TI  - A new dynamic model for bioavailability and cometabolism of micropollutants
      during anaerobic digestion.
AB  - Organic micropollutants (OMPs) are present in wastewater and sludge. Their
      possible impact to the environment contributes to their increasing scientific and
      social interest. Anaerobic digestion has been shown as a potential biological
      process for removal of these compounds. An accurate description of OMP
      distribution in the environmental system can be used to better understand which
      compartment is used for degradation and to improve their depletion in
      conventional wastewater treatment technologies. In this work, we proposed a
      dynamical model with a four-compartment distribution to describe the Polycyclic
      Aromatic Hydrocarbons (PAHs) fate during anaerobic digestion. The model is
      calibrated and validated using experimental data obtained from two continuous
      reactors fed with primary and secondary sludge operated under mesophilic
      conditions. A non-linear least square method was used to optimize the model
      parameters. The resulted model is in accordance with the experimental data. The
      PAH biodegradation rate is well modeled when considering the aqueous fraction
      (including free and sorbed to dissolved/colloidal matter PAHs) as the
      bioavailable compartment. It was also demonstrated in the simulations that the
      PAHs biodegradation is linked to a mechanism of cometabolism. The model proposed
      is potentially useful to better understand the micropollutant distribution,
      predict the fate of PAHs under anaerobic condition and help to optimize the
      operation process for their depletion.

PMID- 21719066
TI  - Role of mass transfer in overall substrate removal rate in a sequential aerobic
      sludge blanket reactor treating a non-inhibitory substrate.
AB  - A laboratory study was undertaken to explore the role of mass transfer in overall
      substrate removal rate and the subsequent kinetic behavior in a glucose-fed
      sequential aerobic sludge blanket (SASB) reactor. At the organic loading rates
      (OLRs) of 2-8 kg chemical oxygen demand (COD)/m3-d, the SASB reactor removed over
      98% of COD from wastewater. With an increase in OLR, the average granule diameter
      (dp=1.1-1.9 mm) and the specific oxygen utilization rate increased; whereas
      biomass density of granules and solids retention time decreased (13-32 d). The
      intrinsic and apparent kinetic parameters were evaluated using break-up and
      intact granules, respectively. The calculated COD removal efficiencies using the
      kinetic model (incorporating intrinsic kinetics) and empirical model
      (incorporating apparent kinetics) agreed well with the experimental results,
      implying that both models can properly describe the overall substrate removal
      rate in the SASB reactor. By applying the validated kinetic model, the calculated
      mass transfer parameter values and the simulated substrate concentration profiles
      in the granule showed that the overall substrate removal rate is intra-granular
      diffusion controlled. By varying different dp within a range of 0.1-3.5 mm, the
      simulated COD removal efficiencies disclosed that the optimal granular size could
      be no greater than 2.5 mm.

PMID- 21719067
TI  - Evaluation of PPCPs removal in a combined anaerobic digester-constructed wetland
      pilot plant treating urban wastewater.
AB  - The removal efficiency of 16 pharmaceuticals and personal care products (PPCPs)
      from urban wastewater (dissolved and particulate phases) was evaluated for the
      first time in a hybrid pilot plant consisting of an upflow anaerobic sludge
      blanket reactor followed by two sequentially connected horizontal flow
      constructed wetlands: a surface flow wetland (SF CW) and a subsurface flow
      wetland (SSF CW). Whereas the PPCP removal associated with the dissolved phase
      exhibited a seasonal pattern, the fraction associated with the suspended solids
      showed less seasonality. In the dissolved phase, the overall removal efficiency
      in summer ranged from 70% to 85% for salicylic acid (SAL), methyl
      dihydrojasmonate, caffeine (CAF), ketoprofen and triclosan, whereas in winter it
      declined for most of the PPCPs to between 30% and 50%, except for CAF and SAL
      (>80%) and carbamazepine and butylated hydroxyl toluene (11-18%). In the
      suspended solids, the removal exceeded 80% for most of the target PPCPs. The
      efficiency of the different treatment steps was also compound-dependent, but the
      SF CW generally exhibited the highest removal efficiency for most of the
      contaminants analyzed. The characterization of the organic matter retained in the
      wetland gravel beds revealed the occurrence of hydrophobic contaminants such as
      phthalate esters and fragrances at moderate concentrations (i.e., up to 3.5 MUg
      kg(-1)), which declined strongly over the course of the different treatment
      steps. In the SF CW, the net mass accumulation rates of tonalide and galaxolide
      were 4 and 23 gy(-1) respectively, whereas in the SSF CW they were 0.3 and 1.8
      gy(-1) respectively.

PMID- 21719068
TI  - Ecogeographic variation in Neandertal dietary habits: evidence from occlusal
      molar microwear texture analysis.
AB  - In the late Middle and early Late Pleistocene, Neandertals inhabited a wide
      variety of ecological zones across western Eurasia during both glacial and
      interglacial times. To elucidate the still poorly understood effects of climatic
      change on Neandertal subsistence patterns, this study employs dental microwear
      texture analysis to reconstruct the diets of Neandertal individuals from various
      sites across their wide temporal and geographic ranges. The results of this study
      reveal environmentally-driven differences in the diets of Neandertal groups.
      Significant differences in microwear signatures, correlated with paleoecological
      conditions, were found among Neandertal groups that lived in open, mixed, and
      wooded environments. In comparison to recent hunter-gatherer populations with
      known, yet diverse diets, the occlusal molar microwear signatures of all the
      Neandertal groups indicate that their diet consisted predominantly of meat.
      However, the results of this study suggest that plant foods did form an important
      part of the diet of at least some Neandertal groups (i.e., those that lived in
      mixed and wooded habitats). Overall, the proportion of plant foods in the
      Neandertal diet appears to have increased with the increase in tree cover.

PMID- 21719069
TI  - An examination of groundwater discharge and the associated nutrient fluxes into
      the estuaries of eastern Hainan Island, China using 226Ra.
AB  - The nutrient concentrations and stoichiometry in a coastal bay/estuary are
      strongly influenced by the direct riverine discharge and the submarine
      groundwater discharge (SGD). To estimate the fluxes of submarine groundwater
      discharge into the Bamen Bay (BB) and the Wanquan River Estuary (WQ) of eastern
      Hainan Island, China, the naturally occurring radium isotope ((226)Ra) was
      measured in water samples collected in the bay/estuary in August 2007 and 2008.
      Based on the distribution of (226)Ra in the surface water, a 3-end-member mixing
      model was used to estimate the relative contributions of the sources to these
      systems. Flushing times of 3.9+/-2.7 and 12.9+/-9.3 days were estimated for the
      BB and WQ, respectively, to calculate the radium fluxes for each system. Based on
      the radium fluxes from groundwater discharge and the Ra isotopic compositions in
      the groundwater samples, the estimated SGD fluxes were 3.4+/-5.0 m(3) s(-1) in
      the BB and 0.08+/-0.08 m(3) s(-1) in the WQ, or 16% and 0.06%, respectively, of
      the local river discharge. Using this information, the nutrient fluxes from the
      submarine groundwater discharge seeping into the BB and WQ regions were
      estimated. In comparison with the nutrient fluxes from the local rivers, the SGD
      derived nutrient fluxes played a vital role in controlling the nutrient budgets
      and stoichiometry in the study area, especially in the BB.

PMID- 21719070
TI  - Directional analysis of CO2 persistence at a rural site.
AB  - Conditional probability was used to establish persistence of CO(2) concentrations
      at a rural site. Measurements extended over three years and were performed with a
      CO(2) continuous monitor and a sodar. Concentrations in the usual range at this
      site were proposed as the truncation level to calculate conditional probability,
      allowing us to determine the extent of CO(2) sequences. Extension of episodes may
      be inferred from these values. Persistence of wind directions revealed two groups
      of sectors, one with a persistence of about 16 h and another of about 9 h.
      Cumulative distribution of CO(2) was calculated in each wind sector and three
      groups, associated with different concentration origins, were established. One
      group was linked to transport and local sources, another to the rural
      environment, and a third to transport of clean air masses. Daily evolution of
      concentrations revealed major differences during the night and monthly analysis
      allowed us to associate group 1 with the vegetation cycle and group 3 with wind
      speed from December to April. Persistence of concentrations was obtained, and
      group 3 values were lower for concentrations above the truncation level, whereas
      persistence of groups 1 and 2 was similar. However, group 3 persistence was, in
      general, between group 1 and 2 persistence for concentrations below the
      truncation level.

PMID- 21719071
TI  - The arsenic for phosphorus swap is accidental, rather than a facultative one, and
      the question whether arsenic is nonessential or toxic is quantitative, not a
      qualitative one.
AB  - Arsenic shares many physicochemical properties with phosphorus, so that arsenic
      can be taken up inadvertently by cells through the pathways for phosphorus. As a
      phosphate analog, arsenate competes with phosphate and enters cells via phosphate
      transporters. In the cell, arsenate can be recognized as a substrate by enzymes
      that usually use phosphate as a substrate. The phosphate for arsenate swap
      results in wasteful 'futile cycles' in metabolic pathways, uncoupled oxidative
      phosphorylation and extreme DNA instability. The disrupting metabolic effects of
      arsenic have an evolutionary meaning, so that all living organisms-from
      chemoautotrophic organisms that grow by reducing or oxidizing arsenic to metazoan
      -carry highly conserved arsenic resistance genes. Arsenic resistance can result
      from different strategies including selective transport to maximize phosphate
      uptake and minimize entry of arsenate, active transport to export arsenate,
      arsenic storage in specialized compartments, enzyme selectivity toward phosphate,
      and increased efficiency of DNA repair systems. None of these strategies is
      infallible, though, and susceptibility to arsenic toxicity varies between taxa in
      many orders of magnitude. Even arsenic-hypertolerant organisms will stop to grow
      and will eventually die when exposed to arsenic over species-specific resistance
      limits. The arsenic for phosphorus swap is an accidental one, it does not warrant
      a conclusion in favor of the essentiality of arsenic to life as we know it.

PMID- 21719072
TI  - Energetic valorization of wood waste: estimation of the reduction in CO2
      emissions.
AB  - This paper investigates the potential CO(2) emission reductions related to a
      partial switch from fossil fuel-based heat and electricity generation to
      renewable wood waste-based systems in Flanders. The results show that
      valorization in large-scale CHP (combined heat and power) systems and co-firing
      in coal plants have the largest CO(2) reduction per TJ wood waste. However, at
      current co-firing rates of 10%, the CO(2) reduction per GWh of electricity that
      can be achieved by co-firing in coal plants is five times lower than the CO(2)
      reduction per GWh of large-scale CHP. Moreover, analysis of the effect of
      government support for co-firing of wood waste in coal-fired power plants on the
      marginal costs of electricity generation plants reveals that the effect of the
      European Emission Trading Scheme (EU ETS) is effectively counterbalanced. This is
      due to the fact that biomass integrated gasification combined cycles (BIGCC) are
      not yet commercially available. An increase of the fraction of coal-based
      electricity in the total electricity generation from 8 to 10% at the expense of
      the fraction of gas-based electricity due to the government support for co-firing
      wood waste, would compensate entirely for the CO(2) reduction by substitution of
      coal by wood waste. This clearly illustrates the possibility of a 'rebound'
      effect on the CO(2) reduction due to government support for co-combustion of wood
      waste in an electricity generation system with large installed capacity of coal-
      and gas-based power plants, such as the Belgian one.

PMID- 21719073
TI  - Speciation and ecological risk of toxic elements in estuarine sediments affected
      by multiple anthropogenic contributions (Guadiana saltmarshes, SW Iberian
      Peninsula): I. Surficial sediments.
AB  - Recent studies have demonstrated that the Guadiana Estuary contains metal
      concentrations in excess of background values. Therefore, this work aims to
      document the potential environmental hazards associated with the availability of
      these metals in this environment of high ecological value. Mineralogical analysis
      shows that the sediments are composed mainly of quartz, albite, and clay minerals
      (illite, smectite, kaolinite, and vermiculite) along with several small, reactive
      compounds (including soluble sulphated salts, Fe-Mn oxyhydroxides, organic
      matter, and pyrite) capable of retaining metals, which can be subsequently
      released, causing environmental degradation. BCR sequential extraction shows that
      As, Cd, Cu, Mn, Pb, and Zn present mobile fractions with respect to the total
      metal content (41, 100, 57, 53, 70, and 69%, respectively) in any of the
      described reactive phases (F1+F2+F3).Calculated environmental risk indices
      demonstrate moderate to considerable ecological risk for almost the entire
      estuary, associated mainly with acid mine drainage from the nearby Iberian Pyrite
      Belt. In addition, the indices highlight several zones of extremely high risk,
      which are related to industrial and urban dumps in the vicinity of the estuary
      and to heavy traffic on the international bridge.

PMID- 21719074
TI  - Organochlorine pesticides, polychlorinated biphenyls and trace elements in wild
      European sea bass (Dicentrarchus labrax) off European estuaries.
AB  - Polychlorinated biphenyls (PCBs) and organochlorine pesticides like dichloro
      diphenyl-trichloroethane (DDTs), hexachlorocyclohexanes (HCHs), aldrin, dieldrin
      and trace elements (Cd, Cu, Se, Pb, Zn and Hg) were analysed in the muscle of
      European sea bass (Dicentrarchus labrax) sampled in Atlantic coastal regions near
      several important European river mouths (Gironde, Charente, Loire, Seine and
      Scheldt). High contamination levels were measured in the muscles of European sea
      bass sampled in the coastal regions near those river mouths (e.g. Sigma ICES
      PCB=133-10,478 MUg kg(-1) lw and Hg=250-2000 MUg kg(-1) dw). The Scheldt and the
      Seine are still among the most contaminated estuaries in Europe. Each region
      presented their specific contamination patterns reflecting different sources due
      to the input of the respective rivers. As fish and fishery products are the main
      contributors of the total dietary intake of organochlorinated pollutants, regular
      consumption of European sea bass with the reported contamination levels may
      represent a significant exposure route for the general human population.

PMID- 21719075
TI  - Immunolocalization of NR1, NR2A, and PSD-95 in rat hippocampal subregions during
      postnatal development.
AB  - Although the expression of NMDARs and synaptic-associated proteins has been
      widely studied, the temporospatial distribution of NMDAR subunits and synaptic
      proteins in different hippocampal subregions during postnatal development still
      lacks detailed information, and the relationship between NR1 or NR2 subunits and
      PSD-95 family proteins is controversial. In this study, we used immunofluorescent
      staining to assess NR1 or NR2A and PSD-95 expressions and the relationship
      between them in CA1, CA3, and DG of rat hippocampus on postnatal (P) days: P0,
      P4, P7, P10, P14, P21, P28, P56. The results showed that from P0 to P56, NR1,
      NR2A, and PSD-95 expressions increased gradually, and the time points of their
      expression peak differed in CA1, CA3, and DG during postnatal development.
      Interestingly, although the expression of PSD-95 was positively correlated to
      both NR1 and NR2A, the NR1 and PSD-95 coexpressed puncta were greatest in CA3,
      while NR2A and PSD-95 coexpressed puncta were greatest in CA1, compared to other
      subregions. Surprisingly, at P21, among different strata of CA1, the area of
      highest expression of NR2A was dramatically changed from stratum pyramidale to
      stratum polymorphum and stratum moleculare, and returned to stratum pyramidale
      gradually on the later observed days again, indicating that P21 may be one
      critical timepoint during postnatal development in CA1. The specific
      temporospatial distribution pattern of NR1, NR2A, and PSD-95 might be related to
      the different physiological functions during postnatal development. Discovering
      the alteration of the relationship between PSD-95 and NMDAR subunits expression
      may be helpful for understanding mechanisms and therapy of neurodegenerative
      diseases.

PMID- 21719076
TI  - Mesenteric ischemia-reperfusion injury: specific impact on different cell
      populations within the jejunal wall in rats.
AB  - The progress of jejunal damage and recovery in the course of mesenteric ischemia
      reperfusion injury in rats at different time periods was investigated. Mesenteric
      ischemia lasting 1h followed by 1h of reperfusion caused a significant
      disintegration of the mucosa, reduction of the muscular layer and diminution of
      the wall thickness. The loss of epithelium included enterocytes, goblet cells and
      Paneth cells. Paradoxically, increasing numbers of serotonin-producing cells and
      the beginning of regenerative processes, expressed by significantly higher
      proliferation, were recorded in the epithelium during this period. Disintegration
      of connective tissue and massive degranulation of serotonin-positive cells were
      found in the lamina propria. After 24h of reperfusion, restitution of the mucosa
      was found, expressed by normal villous morphology and re-epithelialization.
      However, some parameters were still significantly affected even more than in the
      acute phase of reperfusion. In the epithelium, decreased numbers of Paneth cells
      and increased population of serotonin-producing cells were found. The greatest
      proliferation of connective tissue cells and intensified reduction of the
      muscular layer were also detected in this reperfusion period. After 30 days of
      reperfusion, moderate damage remained, but only the increased number of Paneth
      cells and decreased number of serotonin-producing cells in the lamina propria
      were significant.

PMID- 21719077
TI  - Reduced placental FOXP3 associated with subsequent infant allergic disease.

PMID- 21719078
TI  - The effects of an anti-IL-13 mAb on cytokine levels and nasal symptoms following
      nasal allergen challenge.
AB  - BACKGROUND: IL-13 is a key T(H)2 cytokine that is implicated in allergic
      responses. OBJECTIVE: We evaluated the effects of an anti-IL-13-blocking antibody
      compared with placebo on repeated nasal allergen challenge responses in hay fever
      patients out of season. METHODS: We performed a parallel group double-blind study
      of anti-IL-13 (single dose, 6 mg/kg intravenously, n = 16) and placebo (n = 15),
      with an additional open label group given a topical nasal corticosteroid (n = 5).
      Subjects received intranasal timothy grass pollen (Phleum pratense P5 allergen),
      and serial samples of nasal mucosal lining fluid were taken by using synthetic
      absorptive matrix and by nasal lavage. RESULTS: Administration of anti-IL-13 on
      day 1 resulted in a significant decrease in IL-13 levels in synthetic absorptive
      matrix eluates compared with placebo (area under the curve 0-8 hours, change from
      baseline) during the late phase after nasal allergen challenge on day 5 (P < .05)
      and day 7 (P < .01). There were no apparent effects of anti-IL-13 treatment on
      nasal lavage eosinophil numbers or total nasal symptom scores versus placebo.
      However, in a subgroup with high late-phase IL-13 levels at screening, there was
      a trend for a decrease in total nasal symptom scores after nasal allergen
      challenge on day 5, when compared with subjects with low IL-13 levels (P < .10).
      Nasal fluticasone caused suppression of IL-13 (P < .05 on day 5) as well as IL-5
      (P < .01 on day 5) levels in the late phase compared with placebo. CONCLUSIONS:
      Anti-IL-13 had specific pharmacodynamic action in this nasal allergen challenge
      model, causing profound inhibition of nasal lining fluid IL-13 responses. In
      addition, there was a possible effect of anti-IL-13 treatment on total nasal
      symptom scores in a subgroup with high late-phase nasal IL-13 levels at
      screening.

PMID- 21719079
TI  - The impact of lambing stress on post-parturient behaviour of sheep with
      consequences on neonatal homeothermy and survival.
AB  - During lambing the expression of an appropriate behavioural response from both
      the ewe and the lamb are extremely important to lamb survival. The aim of this
      study was to show the effect of length and difficulty of the birth process on the
      expression of maternal and neonatal behaviour with consequences on homeothermy
      and survival of the neonate lamb. Data were collected from 61 Finnish Landrace *
      Rahmani crossbred (second generation) primiparous ewes and their single born
      lambs. Based on the average length of parturition, the ewes were grouped into
      short birth (less than 32.5 min) and long birth (equal to or higher than 32.5
      min) classes. The data recorded include maternal and neonatal behaviour, lamb
      body temperature over the first 3 days of life and survival rate of the neonate
      lamb during the first week after birth. Blood samples were also collected from
      the lamb, pre-suckling and at 24 and 72 h after birth. The obtained sera were
      assayed for thyroid hormones (T(3) and T(4)) that are associated with heat
      production. Ewes that had prolonged and difficult births did not show competent
      maternal behaviour compared to mothers with short and un-complicated deliveries,
      as they were slower to begin grooming their lambs after birth, spent less time
      licking their lambs, made less low-pitched vocalizations and nosing, were more
      likely to show rejection behaviour (10.34 % vs 5.4 %, P < 0.05), and were more
      likely to move away when the lamb sought the udder in an attempt to suck
      (acceptance rate, 55.5 % vs 64.79 %, P < 0.05). Similarly, lambs from a prolonged
      and difficult birth were significantly less vigorous after birth, as they had
      taken more time to stand, reach the udder and to suck successfully. These lambs
      had lower serum concentrations of T(3) and T(4), and they also had a reduced
      ability to maintain body temperature after birth. This effect persisted over the
      first 3 days of life and was associated with higher neonatal mortality in the
      first week after birth (11.54 %), compared to lambs from short and non-stressful
      birth processes (2.86 %, P < 0.01). From the present study, it can be concluded
      that, prolonged deliveries with birthing difficulty were one of the main causes
      of death of large, single-born lambs, as these complications cause the expression
      of inappropriate behavioural responses from both the ewe and neonatal lamb. Thus,
      interventions designed to reduce the incidence of prolonged parturitions are
      likely to be associated with better welfare for the ewe and the lamb and
      consequently improved lamb homeothermy and survival.

PMID- 21719080
TI  - Presynchronization with GnRH 7 days prior to resynchronization with CO-Synch did
      not improve pregnancy rate in lactating dairy cows.
AB  - The objective was to determine the effect of presynchronization with GnRH 7 d
      prior to the initiation of resynchronization with CO-Synch on pregnancy/AI (P/AI)
      of resynchronization in lactating dairy cows, and the effect of GnRH on P/AI from
      previous breeding. All parity Holstein cows (n = 3287) from four dairy farms were
      enrolled. Cows not detected in estrus by 28 +/- 3 d (Day -7) after a previous
      breeding were assigned to receive either GnRH (100 MUg, im; n = 1636) or no GnRH
      (Control; n = 1651). Cows not detected in estrus during the 7 d after GnRH
      underwent pregnancy diagnosis (35 +/- 3 d after previous breeding, Day 0); non
      pregnant cows (n = 1232) in the Control (n = 645) and GnRH (n = 587) groups were
      resynchronized with a CO-Synch protocol. Briefly, cows received 100 MUg GnRH on
      Day 0, 25 mg PGF(2alpha) on Day 7, and 72 h later (Day 10) were given 100 MUg
      GnRH and concurrently inseminated. Serum progesterone concentrations (n = 55
      cows) were elevated in 47.3, 70.9, and 74.5% of cows on Days -7, 0, and 7,
      respectively. The proportion of cows with high progesterone concentrations on Day
      -7 and Day 0 were 44.1% and 88.2% (P < 0.003), and 55.2% and 33.2% (P > 0.1), for
      GnRH and Control groups, respectively. Accounting for significant variables such
      as locations (P < 0.0001) and parity categories (P < 0.05), the P/AI (35 +/- 3 d
      after AI) for resynchronization was not different between GnRH and Control groups
      [26.7% (95% CI: 23.2, 30.5; (157/587) vs 28.4% (95% CI: 25.0, 31.9; (183/645); P
      > 0.1]. There were no significant location by treatment or parity by treatment
      interactions. Accounting for significant variables such as location (P < 0.0001)
      and parity categories (P < 0.001), the P/AI was not different between GnRH and
      Control groups for the previous service [60.2%; 95% CI: 57.9, 62.6; (986/1636) vs
      59.1%; 95% CI: 56.7, 61.5; (976/1651); P > 0.1)]. There were no significant
      location by treatment or parity by treatment interactions. In conclusion, more
      cows presynchronized with GnRH 7 d prior to resynchronization with CO-Synch had
      elevated progesterone concentrations at initiation of resynchronization than
      those not presynchronized. The GnRH treatment 7 d prior to resynchronization with
      CO-Synch, when given 28 +/- 3 d after a previous breeding, did not improve P/AI
      in lactating dairy cows; furthermore, compared to the control, it did not
      significantly affect pregnancy rate from the previous breeding.

PMID- 21719081
TI  - Ovarian activity and uterus organometry in delayed puberty gilts.
AB  - About 30% of the total number of gilts selected for reproduction at the large
      breeding farm units in Vojvodina (Republic of Serbia) are culled due to prolonged
      pre-insemination anoestrus (estrus not detected until 8 mo of age). The aim of
      this study was to provide the answer to the following question: do the culling
      gilts reach cyclic ovarian activity at all? One hundred seventy five culled gilts
      in which external estrus manifestations were not detected by 8 mo of age were
      sacrificed and their reproductive organs were examined for determination of
      sexual maturity (ovaries exhibiting pre-ovulatory follicles 8 to 11 mm in
      diameter, corpora hemorrhagica, corpora lutea and corpora albicantia). Uterine
      weights and horn length were also determined. Functional ovaries were observed in
      107 (61.1%) examined gilts, with 62 animals having one and 45 having two puberty
      ovarian cycles (57.9% and 42.1%, respectively). Pathomorphological changes which
      could result in prolonged pre-insemination anoestrus were not observed on the
      reproductive organs of sexually mature gilts. Our results indicate that most of
      the culling gilts have reached cyclic ovarian activity. The main reason for
      culling due to the absence of external estrus manifestations in sexually mature
      gilts could be inadequate estrus detection technology.

PMID- 21719082
TI  - Evidence-based medicine in bovine, equine and canine reproduction: quality of
      current literature.
AB  - The objective was to evaluate deficits and differences of published literature on
      reproduction in cattle, horses, and dogs. A literature search was conducted in
      the databases Medline and Veterinary Science. Approximately five times more
      articles on clinical bovine reproduction (n = 25 910) were found compared to
      canine (n = 5 015) and equine (n = 5 090) reproduction. For the evaluation of the
      literature, a checklist was used. A subset of 600 articles published between 1999
      and 2008 was randomly selected. After applying exclusion criteria, a total of 268
      trials (86 for cattle, 99 for horses, and 83 for dogs) were evaluated and used
      for further analysis. For the field of canine and equine reproduction, there were
      fewer clinical trials with a control group compared to bovine reproduction
      (cattle 66%, horses 41%, and dogs 41%). For all three species investigated, few
      publications were identified (4%) with the highest level of evidence, i.e.,
      controlled, randomized, and blinded trials, or meta-analyses. In cattle 33% of
      the publications were graded adequate to draw sound conclusions; however, only 7
      and 11% were graded adequate in dogs and horses, respectively. Therefore, the
      veterinarian should always assess the quality of information before implementing
      results into practice to provide best available care for the animals. In
      conclusion, improvement of the quality of well-designed, conducted and reported
      clinical trails in animal reproduction is required.

PMID- 21719083
TI  - Recovery and cryopreservation of epididymal sperm from agouti (Dasiprocta aguti)
      using powdered coconut water (ACP-109c) and Tris extenders.
AB  - The objective was to compare the use of powdered coconut water (ACP-109c; ACP
      Biotecnologia, Fortaleza, CE, Brazil) and Tris extenders for recovery and
      cryopreservation of epididymal sperm from agouti. The caudae epididymus and
      proximal ductus deferens from 10 sexually mature agoutis were subjected to
      retrograde washing using ACP-109c (ACP Biotecnologia) or Tris. Epididymal sperm
      were evaluated for motility, vigor, sperm viability, membrane integrity, and
      morphology. Samples were centrifuged, and extended in the same diluents plus egg
      yolk (20%) and glycerol (6%), frozen in liquid nitrogen, and subsequently thawed
      at 37 degrees C for 1 min, followed by re-evaluation of sperm characteristics.
      The two extenders were similarly efficient for epididymal recovery, with regard
      to the number and quality of sperm recovered. However, for both extenders, sperm
      quality decreased (P < 0.05) after centrifugation and dilution. After sperm
      cryopreservation and thawing, there were (mean +/- SEM) 26.5 +/- 2.6% motile
      sperm with 2.6 +/- 0.2 vigor in the ACP-109c (ACP Biotecnologia) group, which was
      significantly better than 9.7 +/- 2.6% motile sperm with 1.2 +/- 0.3 vigor in
      Tris. In conclusion, agouti epididymal sperm were successfully recovered using
      either ACP-109c (ACP Biotecnologia) or Tris extenders; however, ACP-109c (ACP
      Biotecnologia) was a significantly better extender for processing and
      cryopreserving these sperm.

PMID- 21719084
TI  - Steroidogenesis in primary cultures of neonatal porcine Leydig cells from Duroc
      and Norwegian Landrace breeds.
AB  - Breed differences in steroidogenic activity between primary Leydig cells derived
      from neonatal purebred Duroc and Norwegian Landrace boars were investigated in
      vitro. Concentrations of testosterone, estradiol, androstenone, cortisol and
      progesterone produced into the medium were determined. To explore underlying
      mechanisms the cellular expression of a suite of genes relevant in
      steroidogenesis was measured using reverse transcription and quantitative PCR (RT
      qPCR). Basal steroid concentrations indicated a larger production capacity for
      steroids in unstimulated Duroc cells. Stimulation of the cells with LH increased
      steroid hormone secretion significantly in both breeds in a dose dependent
      manner. Testosterone and androstenone concentrations increased approximately 50-
      and 15-fold, respectively, whereas concentrations of estradiol, cortisol and
      progesterone increased to a lesser extent. At levels of maximal LH stimulation,
      absolute steroid concentrations were higher in Duroc. However, the relative
      increase in hormone concentrations was significantly lower in Duroc cells for
      estradiol, progesterone and cortisol when compared to basal levels. LH exposure
      was associated with a general up-regulation of mRNA levels for steroidogenic
      genes, stronger in Duroc than in Norwegian Landrace. This was in agreement with
      the higher absolute concentrations of steroid hormones measured in culture medium
      from the LH-stimulated Duroc Leydig cells, but did not concur with the fact that
      the relative increase in hormone production was lower in Duroc than in Norwegian
      Landrace Leydig cells for some hormones. It was concluded that breed differences
      in steroid hormone concentrations and gene expression between Norwegian Landrace
      and Duroc are complex and cannot be explained by a simple mechanism of action.

PMID- 21719085
TI  - Dimethylformamide as a cryoprotectant for canine semen diluted and frozen in ACP
      106C.
AB  - The objective was to assess the effect of adding various concentrations of
      dimethylformamide on characteristics of canine semen diluted in powdered coconut
      water (ACP-106C; ACP Biotecnologia, Fortaleza, CE, Brazil) and frozen at -196
      degrees C. Fifteen ejaculates were collected by manual stimulation from five
      adult Boxer dogs. The sperm-rich fraction was diluted in ACP-106C (ACP
      Biotecnologia) containing 10% egg yolk and divided into four aliquots. The
      cryoprotectants used for each aliquot were 6% glycerol (control group; CG) or 2%,
      4%, or 6% dimethylformamide (DF2, DF4, and DF6, respectively). After thawing,
      total motility (mean +/- SEM) for CG (58.4 +/- 24.6) was higher (P < 0.05) than
      that of the other groups (2% dimethylformamide, 24.4 +/- 12.3; 4%
      dimethylformamide, 26.5 +/- 16.1; and 6% dimethylformamide, 21.7 +/- 17.9).
      Furthermore, there was a greater percentage of fast, average, and slow moving
      sperm (assessed with computer-aided semen analysis; CASA) in CG in comparison
      with the other three groups. Therefore, based on concentrations tested in this
      study, dimethylformamide, together with ACP-106C (ACP Biotecnologia) and 10% egg
      yolk as a diluent, yielded unsatisfactory in vitro results for freezing canine
      semen.

PMID- 21719086
TI  - Modelling the porcine oviduct epithelium: a polarized in vitro system suitable
      for long-term cultivation.
AB  - For exploring the processes leading to successful reproduction, differentiated
      long-term in vitro systems modelling the mammalian oviduct are needed. Therefore,
      in the present study culture conditions for primary porcine oviductal epithelial
      cells were optimized with regard to morphological differentiation and usability
      for extended cultivation periods. To evaluate different growth media for the
      primary cells, we used morphological criteria as well as real-time impedance
      measurement. After an initial media testing, the cells were grown on hanging
      membranes and the culture settings (conventionally cultured, serum gradient over
      the membrane and air-liquid interface) were assessed by histology and electron
      microscopy. We proved long-term expression of an oviduct specific marker
      (oviductal glycoprotein 1) and showed a hormone responsiveness of the culture
      system by means of quantitative reverse transcription-PCR. Differentiated
      epithelial cells could reproducibly be cultured up to 6 weeks in an air-liquid
      interface. After 3 weeks of culturing, the cells were clearly polarized and
      exhibited cilia. The model maintains physiological properties such as
      morphological features (mixed cell population of ciliated and secretory cells,
      apical cell-cell contacts typical for columnar epithelial cells) and oviduct
      specific markers showing hormone responsiveness. We established a polarized long
      term in vitro-system of the porcine oviductal epithelium preserving detailed
      features of the porcine oviduct. Therefore, we provide a useful tool to elucidate
      unsolved scientific questions concerning reproductive physiology.

PMID- 21719087
TI  - Influence of vitrification techniques and solutions on the morphology and
      survival of preantral follicles after in vitro culture of caprine ovarian tissue.
AB  - The objective was to compare the efficiency of various vitrification techniques
      and solutions for preserving morphology and viability of preantral caprine
      follicles enclosed in ovarian tissue. Fragments of ovarian cortex were
      cryopreserved by conventional vitrification (CV) in French straws, vitrification
      in macrotubes (MTV), or solid-surface vitrification (SSV). Six solutions
      containing 6 M ethylene glycol, with or without sucrose (SUC; 0.25 or 0.50 M)
      and/or 10% fetal calf serum (FCS) were tested (Experiment I). After 1 wk, samples
      were warmed and preantral follicles were examined histologically. To evaluate
      follicular viability (Experiment II), ovarian fragments were vitrified with the
      three techniques listed above, in a solution containing 0.25 M SUC and 10% FCS.
      After warming, follicles were assessed by the trypan blue dye exclusion test. In
      Experiment III, preantral follicles enclosed in ovarian tissue were vitrified
      using the protocol which yielded the highest percentage of viable preantral
      follicles (SSV with 0.25 M SUC and 10% SFB). After warming, the preantral
      follicles enclosed in ovarian tissue were cultured in vitro and then, were
      analyzed by histology and fluorescence microscopy (calcein-AM and ethidium
      homodimer-1). Every vitrification protocol significantly reduced the percentages
      of morphologically normal follicles relative to the control (88.0%); however, the
      addition of 0.25 M SUC and 10% FCS to the vitrification solution improved
      preservation of follicular morphology (67.4, 67.4, and 72.0% for CV, MTV, and
      SSV, respectively). Although follicular viability after SSV (80.7%) did not
      differ from that in fresh (non-vitrified) ovarian tissues (88.0%), after in vitro
      culture, percentages of viable follicles were significantly reduced (70.0%).
      Percentages of morphologically normal follicles after in vitro culture of
      vitrified ovarian tissue were similar (76.0%) to those in ovarian cortex
      fragments cultured without previous vitrification (83.2%). In conclusion, SSV
      using a solution containing 0.25 M SUC and 10% FCS, was the most efficient method
      for vitrifying caprine ovarian tissue.

PMID- 21719088
TI  - Adaptation of ubiquitin-PNA based sperm quality assay for semen evaluation by a
      conventional flow cytometer and a dedicated platform for flow cytometric semen
      analysis.
AB  - The purpose of semen quality evaluation is to predict the fertility potential of
      the sample in an objective, rapid and inexpensive manner. However, utilization of
      sperm quality biomarkers such as ubiquitin and lectin Arachis hypogaea agglutinin
      (PNA) for flow cytometric semen evaluation might eliminate the need for visual
      assessment by microscopy. Herein, we demonstrate a robust ubiquitin and PNA-based
      semen evaluation conducted on a simple, easy to operate, dedicated sperm flow
      cytometer, EasyCyte Plus (IMV Technologies, L'Aigle, France). Semen samples were
      collected periodically from two dairy bulls, which were subjected to temporary
      scrotal insults to induce variable semen quality. Samples were labeled with
      fluorescently-conjugated anti-ubiquitin antibodies (bind exclusively to the
      surface of defective sperm) and lectin PNA (binds to acrosomal surface in
      prematurely capacitated and acrosome-damaged sperm). Fluorescent properties of
      the samples were measured with a conventional flow cytometer (Becton Dickinson
      FACScan; Becton Dickinson Corp., Franklin Lakes, NJ, USA) and by the EasyCyte
      (IMV Technologies) instrument. Data from the two flow cytometers were positively
      correlated for the percentage of PNA-positive sperm with a damaged acrosome (r =
      0.47; P < 0.001) and the percentage of ubiquitin-positive, defective sperm (r =
      0.68; P < 0.001). Relative intensities of ubiquitin-induced fluorescence in cells
      with high ubiquitin levels were also positively correlated (r = 0.90). The
      proportion of sperm with abnormal morphology was positively correlated with
      ubiquitin-induced fluorescence measured by EasyCyte (IMV Technologies) (r = 0.63;
      P < 0.001). These observations provided a rationale for the adaptation of a dual
      ubiquitin-PNA sperm quality assay for flow cytometric semen evaluation.

PMID- 21719089
TI  - Effect of duration of storage at ambient temperature on fertilizing ability and
      mucus penetration ability of fresh bovine sperm.
AB  - Although the use of fresh semen in the Irish dairy AI industry only accounts for
      5% of total AI usage, this may peak to over 25% during the spring breeding season
      due to the increased demand for Irish proven sires of high genetic merit. The aim
      of this study was to examine the effect of storage of fresh semen for up to 7 d
      at ambient temperature on fertilization and embryo development in vitro, and on
      the ability of sperm to penetrate artificial mucus in vitro. In vitro matured
      bovine oocytes were inseminated with fresh semen stored in a caprogen-based
      diluent, with or without prior Percoll separation. Irrespective of sire, storage
      of fresh semen at ambient temperature for up to 7 d post collection had no effect
      on cleavage rate or blastocyst development after IVF. In addition, blastocyst
      quality, as assessed by the proportion of blastocysts hatching from the zona, was
      not affected by semen storage. Higher numbers of fresh sperm migrated through
      artificial mucus on Day 0 (day of semen collection) compared with frozen-thawed
      sperm. On Day 1 and 2 postcollection there was no difference in the number of
      sperm migrating through the mucus, but storage of sperm at ambient temperature
      for longer than 2 d resulted in a significant decline in their ability to
      penetrate mucus compared with frozen sperm from the same ejaculate. In
      conclusion, bovine sperm retain the ability to fertilize oocytes in vitro for up
      to 7 d following storage at ambient temperature. However, the ability of sperm to
      migrate through artificial mucus in vitro is severely depressed after 2 d storage
      which may have significant implications for the ability of these sperm to reach
      the site of fertilization in vivo after AI.

PMID- 21719090
TI  - Characteristics of the equine embryo and fetus from days 15 to 107 of pregnancy.
AB  - In spite of numerous, substantial advances in equine reproduction, many stages of
      embryonic and fetal morphological development are poorly understood, with no
      apparent single source of comprehensive information. Hence, the objective of the
      present study was to provide a complete macroscopic and microscopic description
      of the equine embryo/fetus at various gestational ages. Thirty-four
      embryos/fetuses were aged based on their crown rump length (CRL), and submitted
      to macroscopic description, biometry, light and scanning microscopy, as well as
      the alizarin technique. All observed developmental changes were chronologically
      ordered and described. As examples of the main observed features, an accentuated
      cervical curvature was observed upon macroscopic examination in all specimens. In
      the nervous system, the encephalic fourth ventricle and the encephalic vesicles
      forebrain, midbrain, and hindbrain, were visualized from Day 19 (ovulation = Day
      0). The thoracic and pelvic limbs were also visualized; their extremities gave
      rise to the hoof during development from Day 27. Development of other structures
      such as pigmented optical vesicle, liver, tail, cardiac area, lungs, and dermal
      vascularization started on Days 25, 25, 19, 19, 34, and 35, respectively. Light
      and scanning microscopy facilitated detailed examinations of several organs,
      e.g., heart, kidneys, lungs, and intestine, whereas the alizarin technique
      enabled visualization of ossification. Observations in this study contributed to
      the knowledge regarding equine embryogenesis, and included much detailed data
      from many specimens collected over a long developmental interval.

PMID- 21719091
TI  - Effects of flunixin meglumine, recombinant bovine somatotropin and/or human
      chorionic gonadotropin on pregnancy rates in Nelore cows.
AB  - The objective was to compare pharmacological strategies aiming to inhibit
      prostaglandin F2 alpha (PGF(2alpha)) synthesis (flunixin meglumine; FM),
      stimulate growth of the conceptus (recombinant bovine somatotropin; bST) and
      progesterone (P(4)) synthesis (human chorionic gonadotropin; hCG), as well as
      their combinations, regarding their ability to improve pregnancy rates in beef
      cattle. Lactating Nelore cows (N = 975), 35 to 70 days postpartum, were
      synchronized and inseminated by timed artificial insemination (TAI) on Day 0. On
      Day 7, cattle were allocated into eight groups and received one of the following
      treatments: saline (S) on Days 7 and 16 (Group Control); S on Day 7 and FM on Day
      16 (Group FM); bST on Day 7 and S on Day 16 (Group bST); bST on Day 7 and FM on
      Day 16 (Group bST + FM); hCG on Day 7 and S on Day 16 (Group hCG); hCG on Day 7
      and FM on Day 16 (Group hCG + FM); bST and hCG on Day 7 and S on Day 16 (Group
      bST + hCG), or bST and hCG on Day 7 and FM on Day 16 (Group bST + hCG + FM). The
      aforementioned treatments were administered at the following doses: 2.2 mg/kg FM
      (Banamine(r); Intervet Schering-Plough, Cotia, SP, Brazil), 500 mg bST
      (Boostin(r); Intervet Schering-Plough), and 2500 IU hCG (Chorulon(r); Intervet
      Schering-Plough). Pregnancy diagnosis was performed 40 days after TAI by
      transrectal ultrasonography. Pregnancy rates were not significantly different
      among treatments. However, there was a main effect of hCG treatment to increase
      pregnancy rates (63.0 vs. 55.4%; P = 0.001). Concentrations of P(4) did not
      differ significantly among groups on Day 7 or on Day 16. However, consistent with
      the higher pregnancy rates, hCG increased P(4) concentrations on Day 16 (10.6 vs.
      9.6 ng/mL, respectively; P = 0.05). We concluded that hCG treatment 7 days after
      TAI improved pregnancy rates of lactating Nelore cows, possibly via a mechanism
      leading to induction of higher P(4) concentrations, or by reducing the luteolytic
      stimulus during maternal recognition of pregnancy.

PMID- 21719092
TI  - Idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis is a devastating, age-related lung disease of
      unknown cause that has few treatment options. This disease was once thought to be
      a chronic inflammatory process, but current evidence indicates that the fibrotic
      response is driven by abnormally activated alveolar epithelial cells (AECs).
      These cells produce mediators that induce the formation of fibroblast and
      myofibroblast foci through the proliferation of resident mesenchymal cells,
      attraction of circulating fibrocytes, and stimulation of the epithelial to
      mesenchymal transition. The fibroblast and myofibroblast foci secrete excessive
      amounts of extracellular matrix, mainly collagens, resulting in scarring and
      destruction of the lung architecture. The mechanisms that link idiopathic
      pulmonary fibrosis with ageing and aberrant epithelial activation are unknown;
      evidence suggests that the abnormal recapitulation of developmental pathways and
      epigenetic changes have a role. In this Seminar, we review recent data on the
      clinical course, therapeutic options, and underlying mechanisms thought to be
      involved in the pathogenesis of idiopathic pulmonary fibrosis.

PMID- 21719093
TI  - Safety of medicines and the use of animals in research.

PMID- 21719094
TI  - Safety of medicines and the use of animals in research.

PMID- 21719095
TI  - Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from
      a randomised, placebo-controlled trial.
AB  - BACKGROUND: Findings of small studies have suggested that short treatments with
      anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding
      preserve beta-cell function and decrease insulin needs in patients with recent
      onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy
      of one such antibody, teplizumab. METHODS: In this 2-year trial, patients aged 8
      35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were
      enrolled and treated at 83 clinical centres in North America, Europe, Israel, and
      India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone
      system, according to computer-generated block randomisation, to receive one of
      three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6
      day full dose) or placebo at baseline and at 26 weeks. The Protege study is still
      underway, and patients and study staff remain masked through to study closure.
      The primary composite outcome was the percentage of patients with insulin use of
      less than 0.5 U/kg per day and glycated haemoglobin A(1c) (HbA(1C)) of less than
      6.5% at 1 year. Analyses included all patients who received at least one dose of
      study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697.
      FINDINGS: 763 patients were screened, of whom 516 were randomised to receive 14
      day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full
      dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose
      group and one patient in the placebo group did not start treatment, so 513
      patients were eligible for efficacy analyses. The primary outcome did not differ
      between groups at 1 year: 19.8% (41/207) in the 14-day full-dose group; 13.7%
      (14/102) in the 14-day low-dose group; 20.8% (22/106) in the 6-day full-dose
      group; and 20.4% (20/98) in the placebo group. 5% (19/415) of patients in the
      teplizumab groups were not taking insulin at 1 year, compared with no patients in
      the placebo group at 1 year (p=0.03). Across the four study groups, similar
      proportions of patients had adverse events (414/417 [99%] in the teplizumab
      groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417
      [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab
      groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group).
      INTERPRETATION: Findings of exploratory analyses suggest that future studies of
      immunotherapeutic intervention with teplizumab might have increased success in
      prevention of a decline in beta-cell function (measured by C-peptide) and
      provision of glycaemic control at reduced doses of insulin if they target
      patients early after diagnosis of diabetes and children. FUNDING: MacroGenics,
      the Juvenile Diabetes Research Foundation, and Eli Lilly.

PMID- 21719097
TI  - New hope for immune intervention therapy in type 1 diabetes.

PMID- 21719098
TI  - Anti-CD3 antibodies for type 1 diabetes: beyond expectations.

PMID- 21719099
TI  - Response to Offline about Great Ormond Street Hospital.

PMID- 21719100
TI  - Construction of the recellularized corneal stroma using porous acellular corneal
      scaffold.
AB  - Acellular porcine cornea stroma (APCS) prepared using pancreatic phospholipase
      A(2) was proven to be promising corneal scaffold. However, its dense
      ultrastructure provides insufficient space that prevents the seeded cells from
      organizing into a functional tissue. In this report, freezing dry APCS (FD-APCS)
      biomaterials containing pores with different sizes were fabricated at different
      pre-freezing temperatures of -10, -80 or -198 degrees C, and the percentage of
      large pores (equivalent circle diameter >=10 MUm) was 93.55%, 69.36%, 35.79%,
      while the small pores (<10 MUm) were account for 6.45%, 30.64%, 64.21%,
      respectively. Both porosity and specific surface area increased in FD-APCS
      fabricated with decreased pre-freezing temperature, and they were dramatically
      higher than those in APCS. The three FD-APCS groups displayed higher permeability
      than APCS, and the -10 degrees C FD-APCS possessed the highest permeability. The
      keratocytes seeded in the FD-APCS construct survived well in vitro, and maximal
      cell proliferation was observed in the -10 degrees C FD-APCS. The light
      transmittance of the FD-APCS-transplanted cornea after interlamellar keratoplasty
      in rabbit eyes displayed no significant difference from the APCS-transplanted or
      native cornea. This study indicated that the porous FD-APCS prepared using
      pancreatic phospholipase A(2) is capable of serving as potential scaffold for
      constructing tissue-engineered cornea with biological properties.

PMID- 21719101
TI  - Polymers for the rapid and effective activation and aggregation of platelets.
AB  - Platelets are responsible for plugging sites of vascular injury, where upon
      activation they spread out and become cross-linked, preventing further blood
      loss. It is desirable to control the activation process on demand for
      applications such as the rapid staunching of blood flow following trauma.
      Polymers are the material of choice in many biological areas, with physical
      properties that allow control of morphology as well as ease of functionalisation
      and production. Herein, polymer microarrays were used to screen a complex human
      fluid (platelet rich plasma) to identify polyacrylates that could be used to
      modulate platelet activation. Several polymers were identified which rapidly
      activated platelets as determined by CD61P binding and subsequent confirmation by
      scanning electron microcopy analysis. This approach enabled a direct comparison
      between the natural agonist collagen and synthetic polymers with respect to the
      activation status of the platelets as well as the number of bound platelets.
      Further investigations under physiological flow demonstrated that the static
      microarray experiments gave viable candidates for potential medical applications
      while specific protein binding to the polymers was identified as a possible mode
      of action. The approach demonstrates the ability of polymer microarrays to
      identify new polymers for specific biological activation events and in this case
      allowed the identification of materials that allowed higher levels of platelets
      to bind in advanced activation states than the natural standard collagen in
      static and flow studies.

PMID- 21719096
TI  - Co-stimulation modulation with abatacept in patients with recent-onset type 1
      diabetes: a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: The immunopathogenesis of type 1 diabetes mellitus is associated with
      T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory
      signal in addition to the main antigen-driven signal. Abatacept modulates co
      stimulation and prevents full T-cell activation. We evaluated the effect of
      abatacept in recent-onset type 1 diabetes. METHODS: In this multicentre, double
      blind, randomised controlled trial, patients aged 6-45 years recently diagnosed
      with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg,
      maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28,
      and monthly for a total of 27 infusions over 2 years. Computer-generated permuted
      block randomisation was used, with a block size of 3 and stratified by
      participating site. Neither patients nor research personnel were aware of
      treatment assignments. The primary outcome was baseline-adjusted geometric mean 2
      h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal
      tolerance test at 2 years' follow-up. Analysis was by intention to treat for all
      patients for whom data were available. This trial is registered at
      ClinicalTrials.gov, NCT00505375. FINDINGS: 112 patients were assigned to
      treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% (95%
      CI 6.1-112) higher at 2 years with abatacept (n=73, 0.378 nmol/L) than with
      placebo (n=30, 0.238 nmol/L; p=0.0029). The difference between groups was present
      throughout the trial, with an estimated 9.6 months' delay (95% CI 3.47-15.6) in C
      peptide reduction with abatacept. There were few infusion-related adverse events
      (36 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six
      [17%] on placebo). There was no increase in infections (32 [42%] patients on
      abatacept vs 15 [43%] on placebo) or neutropenia (seven [9%] vs five [14%]).
      INTERPRETATION: Co-stimulation modulation with abatacept slowed reduction in beta
      cell function over 2 years. The beneficial effect suggests that T-cell activation
      still occurs around the time of clinical diagnosis of type 1 diabetes. Yet,
      despite continued administration of abatacept over 24 months, the decrease in
      beta-cell function with abatacept was parallel to that with placebo after 6
      months of treatment, causing us to speculate that T-cell activation lessens with
      time. Further observation will establish whether the beneficial effect continues
      after cessation of abatacept infusions. FUNDING: US National Institutes of
      Health.

PMID- 21719102
TI  - The use of the fusion protein RGD-HSA-TIMP2 as a tumor targeting imaging probe
      for SPECT and PET.
AB  - The human serum albumin tissue inhibitor of metalloproteinase 2 (HSA-TIMP2) is
      known to possess antitumor activity, which has been attributed to its ability to
      inhibit endothelial cell proliferation by binding to integrin receptors. In this
      study, a fusion protein, cyclic arginine-glycine-aspartate (RGD)-HSA-TIMP2,
      formed by conjugating HSA-TIMP2 with a RGD peptide, and its (123)I- and (68)Ga
      labeled compounds, were synthesized and evaluated with in vivo tumor imaging
      using single photon emission computed tomography (SPECT) and positron emission
      tomography (PET). RGD-HSA-TIMP2 was synthesized by covalent bonding of the RGD
      peptide to the side chain amino groups of HSA-TIMP2 from a two-step reaction
      involving from activation with N-succinimidyl iodoacetate. This conjugation
      improved the anticancer effect of HSA-TIMP2 in cancer cells. The (123)I- and
      (68)Ga-labeled fusion proteins were prepared and subsequently injected into the
      tail veins of mice bearing human glioblastoma cancer U87MG xenografts for SPECT
      and PET imaging and biodistribution studies. Tumor uptake of radioligand was high
      in both the PET images and in the biodistribution studies at 3 h after injection.
      These studies demonstrated that the new fusion protein has potential not only as
      an anticancer agent but also as a radioligand for the diagnosis of tumors.

PMID- 21719103
TI  - Vascular endothelial growth factor (VEGF) and its role in the central nervous
      system: a new element in the neurotrophic hypothesis of antidepressant drug
      action.
AB  - Vascular endothelial growth factor (VEGF) is a well-known cellular mitogen, and a
      vascular growth factor and permeability regulator. It participates in
      physiological and pathological processes of angiogenesis and in the development
      of lymphatic vessels. In addition to the proangiogenic activity, studies of
      recent years have revealed neurotrophic and neuroprotective potential of VEGF
      both in the peripheral and central nervous system. VEGF directly influences
      Schwann cells, neuronal progenitor cells, astrocytes and microglia. This factor
      plays an import role in developmental processes of the nervous tissue since it is
      implicated in neurogenesis and the regulation of neuronal development, and in the
      differentiation and formation of vessels in the brain. VEGF elicits its
      biological effect via an interaction with three VEGF receptor subtypes: VEGFR1,
      VEGFR2 and VEGFR3. In the nervous system, VEGFR2 signaling prevails. VEGF as a
      trophic factor, influencing both vascular endothelial cells and brain cells is a
      focus of the studies on neuropsychiatric disorders and psychotropic drug action.
      Antidepressant drugs were shown to induce hippocampal expression of VEGF. In
      addition, the experiments in animals models of depression have demonstrated that
      VEGFR2 signaling is indispensable for cellular and behavioral response to
      antidepressant drugs. Acquiring a deeper knowledge into the signaling pathways
      engaged in neurogenic and behavioral VEGF actions can unravel new targets for
      more efficient and quick acting antidepressant drugs.

PMID- 21719104
TI  - Multiple approaches to evaluate the toxicity of the biomass fuel cow dung (kanda)
      smoke.
AB  - Cow dung (Kanda) is a major source of energy in rural and urban population of
      developing countries and is burnt in traditional open stoves in confined space of
      kitchen without proper ventilation. In epidemiological studies, biomass fuel
      smoke has been reported to be responsible for several respiratory disorders in
      exposed population. In a laboratory experiment, female wistar rats were exposed
      to kanda smoke for 60 min/day over a period of 12 weeks. Chemical analysis of
      smoke showed the presence of PAHs. The increase in CYP1A1, GST-ya, GST-yc
      expression was found in 12 week exposed lung tissues as compared with controls.
      The exposure to smoke resulted in significant alteration in the BALF cells in the
      form of clustering of alveolar macrophages and giant cell formation with
      vacuolated cytoplasm. The macrophages also showed thickness and villi like
      projections on the cell surface thus reducing their phagocytic activities.
      Histopathological changes in lung tissue were manifested in the form of damage to
      bronchiolar epithelium, edema and thickening of alveolar septa and emphysema
      after 4 and 8 week of exposure. These findings suggest that exposure to kanda
      smoke increases pulmonary tissue damage and may result in various forms of
      respiratory infections in the exposed popultion.

PMID- 21719105
TI  - Hesperetin, a citrus flavonone, protects potentially cadmium induced oxidative
      testicular dysfunction in rats.
AB  - The present study was aimed to evaluate the protective effect of hesperetin (Hp)
      on cadmium (Cd) induced oxidative testicular toxicity in rats. Subcutaneous
      administration of Cd (3mg/kg body weight) for 21 days significantly elevated the
      levels of oxidative stress markers, Cd concentration in testis and lowered the
      levels of enzymatic, non-enzymatic antioxidants and membrane bound enzymes in the
      testicular tissue. Hp administrated orally along with Cd injection for 21 days,
      significantly revert back the status of oxidative stress markers, Cd
      concentration in testis, improved status of antioxidant markers and membrane
      bound enzymes in the testis to near normal level. The histopathological studies
      in the testis of rats also supported that Hp (40 mg/kg) markedly reduced the
      toxicity of Cd and preserved the normal histoarchitecture pattern of the testis.
      Thus, the results suggest that Hp acts as a potent antioxidative agent against Cd
      induced testicular toxicity in rats.

PMID- 21719106
TI  - Enhanced protection against infection with transmissible gastroenteritis virus in
      piglets by oral co-administration of live attenuated Salmonella enterica serovar
      Typhimurium expressing swine interferon-alpha and interleukin-18.
AB  - The enhanced effect of cytokine combinations has been assessed empirically, based
      on their immunobiological mechanisms. However, far less is known of the enhanced
      protection of practical cytokine combinations against viral infection in the
      livestock industry, due to cost and production issues associated with mass
      administration. This study demonstrates the enhanced protection of oral co
      administration of swine interferon-alpha (swIFN-alpha) and interleukin-18 (swIL
      18) against infection with transmissible gastroenteritis virus (TGEV) in piglets
      using attenuated Salmonella enterica serovar Typhimurium as carrier of cytokine
      proteins. A single oral co-administration of S. enterica serovar Typhimurium
      expressing swIFN-alpha and swIL-18 induced enhanced alleviation of the severity
      of diarrhea caused by TGEV infection, compared to piglets administered S.
      enterica serovar Typhimurium expressing swIFN-alpha or swIL-18 alone. This
      enhancement was further observed by the reduction of TGEV shedding and
      replication, and the expression of IFN-stimulated gene products in the intestinal
      tract. The results suggest that the combined administration of the swIFN-alpha
      and swIL-18 cytokines using attenuated S. enterica serovar Typhimurium as an oral
      carrier provides enhanced protection against intestinal tract infection with
      TGEV.

PMID- 21719107
TI  - Glycemic control with insulin glargine plus insulin glulisine versus premixed
      insulin analogues in real-world practices: a cost-effectiveness study with a
      randomized pragmatic trial design.
AB  - BACKGROUND: Cost can be an important consideration, along with safety and
      efficacy, in deciding the most appropriate treatment for patients with type 2
      diabetes. Both basal-bolus and premixed insulin analogue regimens are widely used
      in clinical practice; however, limited information is available regarding cost
      effectiveness. OBJECTIVE: The goal of this study was to compare glycemic control,
      cost-effectiveness, and quality of life effects of insulin glargine plus insulin
      glulisine (glargine/glulisine) versus premixed insulin analogues in real-world
      clinical practice. METHODS: Adults with type 2 diabetes (glycosylated hemoglobin
      [HbA(1c)] >=7.0%) at 3 US endocrinology centers were randomly assigned to receive
      either glargine/glulisine or premixed insulin analogues and continued treatment
      following the centers' usual practice. HbA(1c), weight, insulin dose, concomitant
      oral antidiabetic drug (OAD) usage, and hypoglycemia were evaluated at baseline
      and 3, 6, and 9 months. Medication costs, including costs for all insulin or OAD
      regimens, were estimated using published wholesale acquisition costs. RESULTS: A
      total of 197 patients were randomized to receive glargine/glulisine therapy (n =
      106) or premixed analogue therapy (n = 91). Overall, the mean age was 56 years,
      the mean duration of diabetes was 13 years, with a mean HbA(1c) of 9.25% and mean
      BMI of 35.8 kg/m(2) at baseline. Patients randomized to receive
      glargine/glulisine had a greater mean HbA(1c) reduction from baseline (-2.3%)
      than patients receiving a premixed analogue regimen (-1.7%). Adjusted mean follow
      up HbA(1c) was 6.9% versus 7.5%, respectively (difference, -0.59%; P < 0.01). The
      glargine/glulisine group also used a lower mean number of OADs (0.86 vs 1.14;
      difference, -0.28; P = 0.04) but had a higher weight (240 vs 235 lb; difference,
      4.55 lb; P = 0.03) than the premixed analogue group at follow-up. There were no
      significant differences in daily insulin dose and rates of hypoglycemia. Overall
      medication costs per 1.0% reduction in HbA(1c) were $841 with glargine/glulisine
      and $1308 with premixed analogues. CONCLUSIONS: Overall, treatment with
      glargine/glulisine provided greater improvement in glycemic control and may
      represent a more cost-effective treatment option than premixed regimens for
      patients with type 2 diabetes in real-world clinical practice. However, due to
      the pragmatic trial design, the study concluded before follow-up assessments were
      available for all randomized patients.

PMID- 21719109
TI  - Successful treatment of ultradian or ultra-ultra-rapid cycling: a case report.
AB  - Only three cases of ultradian or ultra-ultra-rapid cycling are to be found in the
      literature till now. The case of a 19-year-old patient is added and her
      successful treatment described. Discontinuation of the antidepressive medication
      and the introduction of lamotrigine and quetiapine resulted in the very
      stabilization of mood which was necessary for successful antidepressive treatment
      with reboxetine.

PMID- 21719110
TI  - The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar
      depression: an open label trial.
AB  - BACKGROUND: Evidence is accumulating to support the presence of redox
      dysregulation in a number of psychiatric disorders, including bipolar disorder.
      This dysregulation may be amenable to therapeutic intervention. Glutathione is
      the predominant non-enzymatic intracellular free radical scavenger in the brain,
      and the most generic of all endogenous antioxidants in terms of action. N
      acetylcysteine (NAC) is a glutathione precursor that effectively replenishes
      brain glutathione. Given the failure of almost all modern trials of
      antidepressants in bipolar disorder to demonstrate efficacy, and the limited
      efficacy of mood stabilisers in the depressive phase of the disorder, this is a
      major unmet need. METHOD: This study reports data on the treatment of 149
      individuals with moderate depression during the 2 month open label phase of a
      randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC
      that examined the use of NAC as a maintenance treatment for bipolar disorder.
      RESULTS: In this trial, the estimated mean baseline Bipolar Depression Rating
      Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8
      week open label treatment phase was 11.1 (SE=0.8). This reduction was
      statistically significant (p<0.001). Improvements in functioning and quality of
      life were similarly evident. CONCLUSION: These open label data demonstrate a
      robust decrement in depression scores with NAC treatment. Large placebo
      controlled trials of acute bipolar depression are warranted.

PMID- 21719111
TI  - Carbon dioxide induction of panic anxiety in schizophrenia with auditory
      hallucinations.
AB  - Panic is commonly co-morbid with schizophrenia. Panic may emerge prodromally,
      contribute to specific psychotic symptoms, and predict medication response. Panic
      is often missed due to agitation, impaired cognition, psychotic symptom overlap
      and limited clinician awareness. Carbon dioxide exposure has been used reliably
      to induce panic in non-psychotic panic subjects, but has not been systematically
      studied in schizophrenia. Eight inpatients with schizophrenia, recent auditory
      hallucinations, none preselected for panic, all on antipsychotic medication,
      received a structured Panic and Schizophrenia Interview (PaSI), assessing DSM-IV
      panic symptoms concurrent with paroxysmal auditory hallucinations. On that
      interview, all eight subjects reported panic concurrent with auditory
      hallucinations. At one sitting, subjects were exposed, in random order, to 35%
      carbon dioxide and to placebo room air, blinded to condition. All subjects
      experienced panic to carbon dioxide, one with limited symptoms. Only one subject
      panicked to placebo. One subject (one of only two without antipanic medication)
      had paroxysmal voices concurrent with induced panic. With added adjunctive
      clonazepam, that patient had marked clinical improvement and no response to
      carbon dioxide re-challenge. This first systematic examination offers preliminary
      evidence that carbon dioxide safely induces panic symptoms in schizophrenia.
      Panic may be prevalent and pathophysiologically significant in schizophrenia with
      auditory hallucinations.

PMID- 21719112
TI  - The innate antiviral immune system of the cat: molecular tools for the
      measurement of its state of activation.
AB  - The innate immune system plays a central role in host defence against viruses.
      While many studies portray mechanisms in early antiviral immune responses of
      humans and mice, much remains to be discovered about these mechanisms in the cat.
      With the objective of shedding light on early host-virus interactions in felids,
      we have developed 12 real-time TaqMan((r)) qPCR systems for feline genes relevant
      to innate responses to viral infection, including those encoding for various
      IFNalpha and IFNomega subtypes, IFNbeta, intracellular antiviral factor Mx, NK
      cell stimulator IL-15 and effectors perforin and granzyme B, as well as Toll-like
      receptors (TLRs) 3 and 8. Using these newly developed assays and others
      previously described, we measured the relative expression of selected markers at
      early time points after viral infection in vitro and in vivo. Feline embryonic
      fibroblasts (FEA) inoculated with feline leukemia virus (FeLV) indicated peak
      levels of IFNalpha, IFNbeta and Mx expression already 6h after infection. In
      contrast, Crandell-Rees feline kidney (CrFK) cells inoculated with feline herpes
      virus (FHV) responded to infection with high levels of IFNalpha and IFNbeta only
      after 24h, and no induction of Mx could be detected. In feline PBMCs challenged
      in vitro with feline immunodeficiency virus (FIV), maximal expression levels of
      IFNalpha, beta and omega subtype genes as well as IL-15 and TLRs 3, 7 and 8 were
      measured between 12 and 24h after infection, whereas expression levels of
      proinflammatory cytokine gene IL-6 were consistently downregulated until 48h post
      inoculation. A marginal upregulation of granzyme B was also observed within 3h
      after infection. In an in vivo experiment, cats challenged with FIV exhibited a
      2.4-fold increase in IFNalpha expression in blood 1 week post infection. We
      furthermore demonstrate the possibility of stimulating feline immune cells in
      vitro with various immune response modifiers (IRMs) already known for their
      immunostimulatory properties in mice and humans, namely Poly IC, Resiquimod (R
      848) and dSLIMTM, a synthetic oligonucleotide containing several unmethylated CpG
      motifs. Stimulation of feline PBMCs with dSLIMTM and R-848 effectively enhanced
      expression of IFNalpha within 12h by factors of 6 and 12, respectively, and Poly
      IC induced an increase in Mx mRNA expression of 28-fold. Altogether, we describe
      new molecular tools and their successful use for the characterization of innate
      immune responses against viruses in the cat and provide evidence that feline
      cells can be stimulated by synthetic molecules to enhance their antiviral defence
      mechanisms.

PMID- 21719113
TI  - T-regulatory cells infected with feline immunodeficiency virus up-regulate
      programmed death-1 (PD-1).
AB  - CD4(+)CD25(+) regulatory T (Treg) cells play a crucial role in the regulation of
      peripheral tolerance and immune response. Treg cells influence the nature and
      magnitude of immune responses, in particular to chronic infections with viruses
      such as HIV in humans and feline immunodeficiency virus (FIV) in cats. The co
      stimulatory molecule programmed (cell) death-1 (PD-1) is expressed on T cells and
      antigen presenting cells. Interaction with its ligand, PD-L1, reduces CD4(+) and
      CD8(+) T-cell function, and may lead to dysfunction or exhaustion of T cells. In
      this study, lymphocytes from blood or lymph nodes of healthy cats were mock or
      FIV infected, and sorted into CD4(-), CD4(+)CD25(+) and CD4(+)CD25(-) subsets.
      Expression of FoxP3, PD-1 and PD-L1 mRNA relative to the housekeeping genes beta
      actin and tyrosine 3-monooxygenase was determined by quantitative reverse
      transcriptase PCR assays. Results indicated that CD4(+)CD25(+) cells had higher
      transcript numbers of FoxP3, PD-1 and PD-L1 than CD4(-) and CD4(+)CD25(-) cells
      (P<0.05). Acute in vitro FIV infection increased expression of FoxP3, PD-1 and PD
      L1 in CD4(+)CD25(+) and CD4(+)CD25(-) cells, with highest relative expression in
      CD4(+)CD25(+) cells. These findings suggest that up-regulation of PD molecules in
      acutely FIV-infected lymphocytes may contribute to the immunosuppressive function
      of Treg cells in lentiviral infection.

PMID- 21719114
TI  - Characterization of the interferon gamma response to Lawsonia intracellularis
      using an equine proliferative enteropathy challenge (EPE) model.
AB  - Lawsonia intracellularis is the etiological agent of infectious intestinal
      hyperplasia for which several clinical diseases have been described including
      proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While
      initially recognized as the causative agent of PE in pigs, L. intracellularis is
      now viewed as an emerging cause of intestinal hyperplasia in a wide range of
      mammalian species, including horses. Equine proliferative enteropathy (EPE) has
      been reported worldwide though definitive diagnosis is difficult and the
      epidemiology of the disease remains poorly understood. Weanlings, in particular,
      appear to be most at risk for infection, though the reasons for their particular
      susceptibility is unknown. Using an infectious challenge model for EPE, we
      demonstrate that EPE, like porcine proliferative enteropathy, can exhibit three
      clinical forms: classical, subclinical and acute. Out of six pony weanlings, one
      developed signs of classic EPE, one developed acute EPE, and two developed
      subclinical EPE. Attempts to induce pharmacological stress through the use of
      dexamethasone failed to have any effect on outcome. Peripheral blood cells
      collected from those weanlings that developed clinical EPE exhibited decreased
      expression of interferon-gamma (IFN-gamma) following in vitro stimulation with L.
      intracellularis. By contrast, those weanlings that did not develop clinical
      disease generated a robust IFN-gamma response. These results indicate IFN-gamma
      likely plays a significant role in protection from disease caused by L.
      intracellularis in the equid.

PMID- 21719115
TI  - Genetic determinants of pathogenesis by feline infectious peritonitis virus.
AB  - Feline infectious peritonitis (FIP) is a fatal, immune-augmented, and progressive
      viral disease of cats associated with feline coronavirus (FCoV). Viral genetic
      determinants specifically associated with FIPV pathogenesis have not yet been
      discovered. Viral gene signatures in the spike, non-structural protein 3c, and
      membrane of the coronavirus genome have been shown to often correlate with
      disease manifestation. An "in vivo mutation transition hypothesis" is widely
      accepted and postulates that de novo virus mutation occurs in vivo giving rise to
      virulence. The existence of "distinct circulating avirulent and virulent strains"
      is an alternative hypothesis of viral pathogenesis. It may be possible that viral
      dynamics from both hypotheses are at play in the occurrence of FIP. Epidemiologic
      data suggests that the genetic background of the cat contributes to the
      manifestation of FIP. Further studies exploring both viral and host genetic
      determinants of disease in FIP offer specific opportunities for the management of
      this disease.

PMID- 21719116
TI  - Use of recombinant interferon omega in feline retrovirosis: from theory to
      practice.
AB  - Type-I interferons (IFNs) are cytokines that have non-specific antiviral
      activity, participating mostly in innate defense mechanisms. Their administration
      has been proposed to treat several viral and immunomediated diseases as an
      immunomodulatory therapy. Due to its availability, recombinant human interferon
      alpha (rHuIFN-alpha) has been studied in relation to feline retrovirosis, both in
      vitro and in vivo. However, IFNs are species-specific and antibodies have been
      shown to develop in response to the high rHuIFN-alpha doses necessary for an
      effective therapy. A recombinant feline IFN has been developed, which has been
      characterized as interferon-omega (rFeIFN-omega), designed to overcome these
      problems. Nonetheless, very few studies have been undertaken to evaluate its
      efficacy in cats naturally infected with FIV or FeLV. In an initial study, we
      here demonstrated that rFeIFN-omega can dramatically improve the clinical
      condition of infected cats, and induce improvement of hematologic parameters.
      Minor changes or no change was observed for hypergammaglobulinemia, CD4/CD8
      ratio, proviral load, viremia and RT activity, suggesting that the overall effect
      of IFN was on innate immunity. More studies are needed in order to better
      understand its in vivo mechanisms.

PMID- 21719117
TI  - Evolutionarily conserved T-cell epitopes on FIV for designing an HIV/AIDS
      vaccine.
AB  - This review will discuss the current state of the human HIV-1 vaccine trials
      including the safety consideration of vaccine composition and difficulties in
      determining and defining protective immunity and epitopes to HIV-1. Vaccines in
      animal models of lentivirus infection are compared. In particular, the findings
      from the prototype FIV vaccine and the HIV-1 protein immunizations studies in
      cats are discussed, as well as the resulting research regarding a potential HIV-1
      vaccine design based on evolutionarily conserved T-cell epitopes.

PMID- 21719118
TI  - Trigeminal satellite cells express functional calcitonin gene-related peptide
      receptors, whose activation enhances interleukin-1beta pro-inflammatory effects.
AB  - Calcitonin gene-related peptide (CGRP) is the main mediator of trigeminal pain
      signal. Functional CGRP receptors were detected in trigeminal satellite cells, a
      specialized type of glia found within the sensory ganglia. CGRP displayed modest
      pro-inflammatory effects per se on trigeminal satellite cells, while it
      significantly enhanced IL-1beta actions, increasing the expression and activity
      of cycloxygenase 2 as well as the expression of the inducible form of nitric
      oxide synthase and IL-1beta. CGRP effects were reverted by a specific CGRP
      receptor antagonist and mimicked by elevation of intracellular cAMP levels. CGRP
      exerted also minor proinflammatory effects on cortical astrocytes.

PMID- 21719119
TI  - Relation between language, audio-vocal psycholinguistic abilities and P300 in
      children having specific language impairment.
AB  - Specific language impairment is a relatively common developmental condition in
      which a child fails to develop language at the typical rate despite normal
      general intellectual abilities, adequate exposure to language, and in the absence
      of hearing impairments, or neurological or psychiatric disorders. There is much
      controversy about the extent to which the auditory processing deficits are
      important in the genesis specific language impairment. The objective of this
      paper is to assess the higher cortical functions in children with specific
      language impairment, through assessing neurophysiological changes in order to
      correlate the results with the clinical picture of the patients to choose the
      proper rehabilitation training program. SUBJECTS AND METHOD: This study was
      carried out on 40 children diagnosed to have specific language impairment and 20
      normal children as a control group. All children were subjected to the assessment
      protocol applied in Kasr El-Aini hospital. They were also subjected to a language
      test (receptive, expressive and total language items), the audio-vocal items of
      Illinois test of psycholinguistic (auditory reception, auditory association,
      verbal expression, grammatical closure, auditory sequential memory and sound
      blending) as well as audiological assessment that included peripheral
      audiological and P300 amplitude and latency assessment. The results revealed a
      highly significant difference in P300 amplitude and latency between specific
      language impairment group and control group. There is also strong correlations
      between P300 latency and the grammatical closure, auditory sequential memory and
      sound blending, while significant correlation between the P300 amplitude and
      auditory association and verbal expression. CONCLUSION: Children with specific
      language impairment, in spite of the normal peripheral hearing, have evidence of
      cognitive and central auditory processing defects as evidenced by P300 auditory
      event related potential in the form of prolonged latency which indicate a slow
      rate of processing and defective memory as evidenced by small amplitude. These
      findings affect cognitive and language development in specific language
      impairment children and should be considered during planning the intervention
      program.

PMID- 21719120
TI  - Prognostic validity of dichotic multiple frequencies auditory steady-state
      responses versus distortion product otoacoustic emissions in hearing screening of
      high risk neonates.
AB  - OBJECTIVE: To determine the validity of dichotic multiple frequencies auditory
      steady-state responses (ASSR) as a hearing screening technique versus using
      distortion product otoacoustic emissions (DPOAEs) among high-risk neonates.
      METHODS: A cross sectional study was performed on 118 high-risk neonates by means
      of dichotic multiple frequencies ASSR and DPOAE for hearing screening. DPOAE
      results were used as the standard for hearing screening in parallel with ASSR.
      Dichotic multiple frequencies ASSR results were analyzed by means of F-value of
      less or greater than 0.05 criteria as a pass-fail for the responses. Dichotic
      multiple ASSR hearing screening technique was considered in two intensity levels
      at 40 and 70 dB HL. The ASSRs thresholds were measured in high risk neonates with
      and without hearing deficits as determined by DPOAES. The results of ASSR and
      DPOAE were compared to be gathered by contingency table in order to obtain
      sensitivity, specificity and other different statistical values. Average
      performing times for the tests were analyzed. RESULTS: The specificity of
      dichotic multiple ASSR was 92.6%, 93.8% and the sensitivity was 71.6%, 62.2% at
      the 70 and 40 dB hearing levels, respectively. Mean ASSR thresholds for normal
      hearing infants at an average corrected age of 6 days were 32.2 +/- 12.2, 29.8 +/
      10.2, 26.2 +/- 11.4 and 30.4 +/- 10.8 dB HL for 0.5, 1, 2 and 4 kHz,
      respectively. The average times for performing the tests were 18.7 and 32.9 min
      respectively. CONCLUSIONS: ASSR with this special paradigm is a fairly desirable
      method for hearing screening of high-risk neonates. There is good concordance
      between ASSRs and DOPAEs results among high risk neonates referred for hearing
      screening. The sensitivity and specificity of this test is sufficient for hearing
      screening in high risk neonates. This test could be valuable for rapid
      confirmation of normal thresholds. As long as further research have not been
      conducted on ASSR, great caution should be made to interpret the results of ASSR
      as a hearing screening technique in young infants and also additional techniques
      such as the tone-evoked ABRs should be used to cross-check results. It's still
      too soon to recommend ASSRs as a standalone electrophysiologic measure of hearing
      thresholds in infants.

PMID- 21719121
TI  - Maternal smoking during pregnancy: impact on otoacoustic emissions in neonates.
AB  - OBJECTIVES: To determine the effect of maternal smoking during pregnancy on
      transient evoked otoacoustic emissions levels in neonates. METHODS: This was a
      cross-sectional study investigating neonates in the maternity ward of a
      university hospital in the city of Sao Paulo, Brazil. A total of 418 term
      neonates without prenatal or perinatal complications were evaluated. The neonates
      were divided into two groups: a study group, which comprised 98 neonates born to
      mothers who had smoked during pregnancy; and a control group, which comprised 320
      neonates born to mothers who had not. In order to compare the two ears and the
      two groups in terms of the mean overall response and the mean transient evoked
      otoacoustic emissions in response to acoustic stimuli delivered at different
      frequencies, we used analysis of variance with repeated measures. RESULTS: The
      mean overall response and the mean frequency-specific response levels were lower
      in the neonates in the study group (p<0.001). The mean difference between the
      groups was 2.47 dB sound pressure level (95% confidence interval: 1.47-3.48).
      CONCLUSIONS: Maternal smoking during pregnancy had a negative effect on cochlear
      function, as determined by otoacoustic emissions testing. Therefore, pregnant
      women should be warned of this additional hazard of smoking. It is important that
      smoking control be viewed as a public health priority and that strategies for
      treating tobacco dependence be devised.

PMID- 21719122
TI  - The site of origin and expansive routes of juvenile nasopharyngeal angiofibroma
      (JNA).
AB  - OBJECTIVE: Juvenile nasopharyngeal angiofibroma (JNA) is a rare vascular tumor of
      the nasopharynx occurring in young males. The aim of this study was attempt to
      find out the site of origin and the common expansion routes of JNA. METHODS: The
      CT examinations of 46 untreated patients with histologically proven JNA were
      retrospectively analyzed. Evidence of tumor spreading of the locations are those
      following CT characteristics: (a) expansion and/or erosion of bony wall; (b)
      obliteration of normal fatty planes. In addition, three dimensional
      reconstruction technology was used to make further study. RESULTS: The pterygoid
      canal was affected in all untreated cases and therefore was considered as the
      origin of JNA. Nineteen patients' tumors (41.3%) originated from the front part
      of pterygoid canal and the other 27 ones (58.7%) from the post part of pterygoid
      canal. Pterygoid canal, choanae and nasal cavity are the three most common sites
      of JNA. CONCLUSION: The possible site of origin is pterygoid canal. After
      originating from this point, the tumor will invade sphenopalatine foramen,
      sphenoid sinus and pterygopalatine fossa first, and then into adjacent structure
      through aforementioned three sites.

PMID- 21719123
TI  - Analyzing key performance indicators (KPIs) for E-commerce and Internet marketing
      of elderly products: a review.
AB  - With the transformation of its population structure and economic environment,
      Taiwan is rapidly becoming an aging society. There is a growing need for elderly
      products, and therefore the operation of web shops that sell elderly products is
      important. In an era which values performance management, searching for key
      performance indicators (KPIs) helps to reveal, if the goals of a web shop are
      achieved. In the current study, researchers adopted the constructs of the
      Balanced Scorecard (BSC) to evaluate web shop performance. Additionally, the
      Delphi method, along with questionnaires, was used to develop 29 indicators.
      Finally, the decision making trial and evaluation laboratory (DEMATEL) method
      assisted in identifying the level of importance of the constructs, in which
      "internal process" ranked top, followed by "learning and growth", "customer", and
      "financial". "Internal process" was the key construct that impacted other
      factors, while "customer" was an important construct affected by other factors.
      By understanding the influences and relationships among the constructs,
      enterprises can conduct additional monitoring and management to achieve functions
      of prevention, continuous improvement, and innovation in order to shape their
      core competence.

PMID- 21719124
TI  - Measuring function in older adults with co-morbid illnesses who are undergoing
      coronary artery bypass graft (CABG) surgery.
AB  - Measuring function in individuals post CABG surgery is difficult because of the
      diversity of functional abilities/disabilities. This study compared the human
      activity profile (HAP) to the medical outcome study short form (SF-36v2TM), in
      individuals with functional co-morbidities undergoing CABG surgery. The sample
      consisted of 84 men and 17 women, with a mean age of 63 years. The majority
      (n=83, 82%) had three to six co-morbid illnesses. There were significant negative
      correlations between the functional co-morbidity index (FCI) scores and the HAP,
      maximum activity score (MAS) (r=-0.32, p=0.002), adjusted activity score (AAS)
      (r=-0.29, p=0.004), indicating that function was lower in individuals with higher
      co-morbidities. There was a non-significant negative correlation between FCI
      scores and physical component summary (PCS) scores of the SF-36v2TM (r=-0.19,
      p=0.07). Results of this study are consistent with those of others who reported a
      growing incidence of older individuals with co-morbid factors undergoing CABG
      surgery. Generic instruments that have traditionally been used to measure
      function may not be sensitive enough to differences in function in individuals
      with co-morbidities. Results of this study imply that the HAP is more sensitive
      than the PCS to these differences, but further research evaluating the HAP in
      populations with co-morbid burden is necessary.

PMID- 21719125
TI  - Critical infarct size to induce ventricular remodeling, cardiac dysfunction and
      heart failure in rats.

PMID- 21719126
TI  - Impact of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular
      outcomes in patients with stable atherothrombosis or multiple risk factors.
AB  - BACKGROUND: We aimed to assess whether the use of non-steroidal anti-inflammatory
      drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events
      in stable patients with established atherothrombosis or multiple risk factors.
      METHODS: We analysed the 23,728 European patients of the REACH Registry; 20,588
      (86.8%) had established atherothrombotic disease and 3140 (13.2%) had multiple
      risk factors only. Aspirin (ASA) and/or NSAIDs use was determined at enrolment
      and ischemic events were recorded over two years of follow-up. cMACCE was defined
      as the composite of CV death, MI or stroke. Bleeding was defined as any bleeding
      leading to both hospitalisation and transfusion. RESULTS: The mean age of
      population was 67.2+/-9.8years. At baseline, 1573 patients (6.6%) received NSAIDs
      and 15,395 (64.9%) received ASA. Four groups were defined: 1) no ASA/no NSAIDs,
      2) ASA only, 3) NSAIDs only, 4) NSAIDs+ASA, with 7722 (32.5%), 14,433 (60.8%),
      611 (2.6%) and 962 (4.1%) patients in these groups, respectively. Among the
      22,028 (92.8%) with complete 2-year follow-up, 683 (3.2%) died from CV causes,
      while 395 (1.9%) had MI, 665 (3.1%) stroke, 1651 (7.6%) cMACCE and 199 (1.0%)
      bleeding. After adjustment, NSAID use was independently associated with an
      increased risk of stroke (OR 1.635; 95% CI 1.239-2.159, p<0.001), and a trend
      towards an increased bleeding rate (OR 1.554; CI 95% 0.960-2.51, p=0.07). No
      association was found between NSAID use and MI or MACCE. CONCLUSIONS: In stable
      atherothrombosis patients, the use of NSAIDs appears to be independently
      associated with an increased cerebrovascular event risk.

PMID- 21719127
TI  - Cardiac rupture in a patient with an acute myocardial infarction and extensive
      fatty infiltration of the heart ("adipositas cordis").

PMID- 21719128
TI  - Malnutrition, anemia and renal dysfunction in patients with Chagasic
      cardiomyopathy.

PMID- 21719129
TI  - High-sensitivity C-reactive protein in the low- and intermediate-Framingham risk
      score groups: analysis with 18F-fluorodeoxyglucose positron emission tomography.
AB  - OBJECTIVES: To evaluate vascular inflammation according to high-sensitivity C
      reactive protein (hsCRP) levels in the low- (<10%) and intermediate- (10%-20%)
      Framingham risk score (FRS) groups using (18)F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET)/CT, which reflects vascular inflammation and vulnerable
      atherosclerotic plaque. METHODS: We measured hsCRP levels and traditional
      cardiovascular risk factors in 142 non-diabetic subjects without history of
      cardiovascular disease. To assess the vascular influence of hsCRP on each FRS
      category, we compared carotid intima-media thickness (CIMT), brachial-ankle pulse
      wave velocity (baPWV), and vascular inflammation, which was represented as the
      target-to-background ratio (TBR) measured using FDG-PET/CT. RESULTS: In both low-
      and intermediate-FRS categories, mean TBR values in subjects with higher hsCRP
      levels (>=2mg/L) were significantly increased compared to those with lower hsCRP
      levels (<2mg/L) (P=0.001, P<0.001, respectively). However, baPWV and CIMT values
      did not significantly differ according to hsCRP levels in the same FRS
      categories. Mean TBR levels positively correlated with FRS, body mass index
      (BMI), whereas negatively correlated with HDL-cholesterol. Multiple stepwise
      regression analyses showed that hsCRP, LDL-cholesterol, BMI, and insulin
      resistance were independently associated with mean TBR values (R(2)=0.414).
      CONCLUSIONS: In both intermediate and low FRS risk groups, vascular inflammation
      measured using FDG-PET/CT was increased in individuals with higher hsCRP levels
      compared to those with lower hsCRP.

PMID- 21719130
TI  - Bone marrow-derived mesenchymal stem cells protected rat cardiomyocytes from
      premature senescence.

PMID- 21719131
TI  - The impact of minimum legal drinking age laws on alcohol consumption, smoking,
      and marijuana use: evidence from a regression discontinuity design using exact
      date of birth.
AB  - This paper uses a regression discontinuity design to estimate the impact of the
      minimum legal drinking age laws on alcohol consumption, smoking, and marijuana
      use among young adults. Using data from the National Longitudinal Survey of Youth
      (1997 Cohort), we find that granting legal access to alcohol at age 21 leads to
      an increase in several measures of alcohol consumption, including an up to a 13
      percentage point increase in the probability of drinking. Furthermore, this
      effect is robust under several different parametric and non-parametric models. We
      also find some evidence that the discrete jump in alcohol consumption at age 21
      has negative spillover effects on marijuana use but does not affect the smoking
      habits of young adults. Our results indicate that although the change in alcohol
      consumption habits of young adults following their 21st birthday is less severe
      than previously known, policies that are designed to reduce drinking among young
      adults may have desirable impacts and can create public health benefits.

PMID- 21719132
TI  - Recessions are bad for workplace safety.
AB  - Workplace accidents are an important economic phenomenon. Yet, the pro-cyclical
      fluctuations in workplace accidents are not well understood. They could be
      related to fluctuations in effort and working hours, but workplace accidents may
      also be affected by reporting behavior. Our paper uses unique data on workplace
      accidents from an Austrian matched worker-firm dataset to study in detail how
      economic incentives affect workplace accidents. We find that workers who reported
      an accident in a particular period of time are more likely to be fired later on.
      And, we find support for the idea that recessions influence the reporting of
      moderate workplace accidents: if workers think the probability of dismissals at
      the firm level is high, they are less likely to report a moderate workplace
      accident.

PMID- 21719133
TI  - Translational control is a major contributor to hypoxia induced gene expression.
AB  - BACKGROUND AND PURPOSE: Hypoxia is a common feature of solid tumors that is
      associated with an aggressive phenotype, resistance to therapy and poor
      prognosis. Major contributors to these adverse effects are the transcriptional
      program activated by the HIF family of transcription factors as well as the
      translational response mediated by PERK-dependent phosphorylation of eIF2alpha
      and inhibition of mTORC1 activity. In this study we determined the relative
      contribution of both transcriptional and translational responses to changes in
      hypoxia induced gene expression. MATERIAL AND METHODS: Total and efficiently
      translated (polysomal) mRNA was isolated from DU145 prostate carcinoma cells that
      were exposed for up to 24 h of hypoxia (<0.02% O(2)). Changes in transcription
      and translation were assessed using affymetrix microarray technology. RESULTS:
      Our data reveal an unexpectedly large contribution of translation control on both
      induced and repressed gene expression at all hypoxic time points, particularly
      during acute hypoxia (2-4 h). Gene ontology analysis revealed that gene classes
      like transcription and signal transduction are stimulated by translational
      control whereas expression of genes involved in cell growth and protein
      metabolism are repressed during hypoxic conditions by translational control.
      CONCLUSIONS: Our data indicate that translation influences gene expression during
      hypoxia on a scale comparable to that of transcription.

PMID- 21719134
TI  - Regeneration of irradiated salivary glands with stem cell marker expressing
      cells.
AB  - BACKGROUND: Stem cell therapy could be a potential way for reducing radiation
      induced hyposalivation and improving the patient's quality of life. However, the
      identification and purification of salivary gland stem cells have not been
      accomplished. This study aims to better characterize the stem/progenitor cell
      population with regenerative potential residing in the mouse salivary gland.
      METHODS: Mouse submandibular gland tissue, isolated cells and cultured 3 day old
      salispheres were tested for their expression of stem cell markers c-Kit, CD133,
      CD49f, and CD24 using immunohistochemistry for tissue and flow cytometry for
      cells. Mice were locally irradiated with a single dose of 15 Gy and transplanted
      with cells expressing defined markers. RESULTS: Cells expressing known stem cell
      markers are localized in the larger ducts of the mouse salivary gland. Isolated
      cells and cells from day 3 salispheres also express these markers: c-Kit (0.058%
      vs. 0.65%), CD133 (6% vs. 5%), CD49f (78% vs. 51%), and CD24 (60% vs. 60%,
      respectively). Intraglandular transplantation of these cells into irradiated
      salivary glands of mice resulted in stem cell marker-specific recovery of
      salivary gland function. CONCLUSIONS: Different stem cell-associated markers are
      expressed in mouse salivary gland cells, which upon transplantation are able to
      regenerate the irradiation damaged salivary gland.

PMID- 21719135
TI  - Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances
      cellular radiation resistance.
AB  - BACKGROUND: Cancer stem cells are thought to be a radioresistant population and
      may be the seeds for recurrence after radiotherapy. Using tumorigenic clones of
      retroviral immortalized human mesenchymal stem cell with small differences in
      their phenotype, we investigated possible genetic expression that could explain
      cancer stem cell radiation resistance. METHODS: Tumorigenic mesenchymal cancer
      stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for
      clonogenic surviving fraction. Altered gene expression before and after 2 Gy was
      assessed by Affymetric exon chip analysis and further validated with q-RT-PCR
      using TaqMan probes. RESULTS: The CE8 clone was more radiation resistant than the
      BB3 clone. From a pool of 15 validated genes with altered expression in the CE8
      clone, we found the enzyme nicotinamide N-methyltransferase (NNMT) more than 5
      fold upregulated. In-depth pathway analysis found the genes involved in cancer,
      proliferation, DNA repair and cell death. CONCLUSIONS: The higher radiation
      resistance in clone CE8 is likely due to NNMT overexpression. The higher levels
      of NNMT could affect the cellular damage resistance through depletion of the
      accessible amounts of nicotinamide, which is a known inhibitor of cellular DNA
      repair mechanisms.

PMID- 21719136
TI  - Comparison of (immuno-)fluorescence data with serial [18F]Fmiso PET/CT imaging
      for assessment of chronic and acute hypoxia in head and neck cancers.
AB  - PURPOSE: Both, acute and chronic hypoxia can have unfavorable impacts on tumor
      progression and therapy response. The aim of this study was to optimize a
      macroscopic technique for the quantification of acute and chronic hypoxia (Wang
      model assessment of serial [(18)F]Fmiso PET/CT imaging) by comparing with a
      microscopic technique [(immuno-)fluorescence staining in tumor cryosections].
      MATERIALS AND METHODS: Tumor pieces from the human squamous cell carcinoma lines
      from the head and neck FaDu and CAL33 were xenografted into the hind leg of NMRI
      nu/nu mice. Tumor-bearing mice were placed on an in-house developed multi-point
      fixation system and subjected to two consecutive dynamic [(18)F]Fmiso PET/CTs
      within a 24h interval. The Wang model was applied to SUV (standard uptake values)
      to quantify the fractions of acute and chronic hypoxia. Hypoxia subtypes were
      also assessed in vital tumor tissue of cryosections from the same tumors for
      (immuno-)fluorescence distributions of Hoechst 33342 (perfusion), pimonidazole
      (hypoxia), and CD31 (endothelium) using pattern recognition in microcirculatory
      supply units (defined as vital tumor tissue area supplied by a single
      microvessel). RESULTS: Using our multi-point fixation system, acceptable co
      registration (registration errors epsilon ranged from 0.34 to 1.37) between
      serial PET/CT images within individual voxels was achieved. The Wang model
      consistently yielded higher fractions of acute hypoxia than the MCSU method.
      Through specific modification of the Wang model (Wang(mod)), it was possible to
      reduce the fraction of acute hypoxia. However, there was no significant
      correlation between the fractions of acute hypoxia in individual tumors assessed
      by the Wang(mod) model and the MCSU method for either tumor line (FaDu: r=0.68,
      p=0.21 and CAL33: r=0.71, p=0.18). This lack of correlation is most-likely due to
      the difference between the non-linear uptake of [(18)F]Fmiso and the spatial
      assessment of MCSUs. CONCLUSIONS: Whether the Wang model can be used to predict
      radiation response after serial [(18)F]Fmiso PET imaging, needs to be confirmed
      in experimental and clinical studies.

PMID- 21719137
TI  - The poly(ADP-Ribose) polymerase inhibitor ABT-888 reduces radiation-induced
      nuclear EGFR and augments head and neck tumor response to radiotherapy.
AB  - BACKGROUND AND PURPOSE: Current therapies for head and neck cancer frequently are
      not curative, necessitating novel therapeutic strategies. Thus, we studied
      whether inhibition of poly(ADP-Ribose) polymerase (PARP), a key DNA repair
      enzyme, could improve efficacy of radiotherapy in human head and neck cancer.
      MATERIALS AND METHODS: UM-SCC1, UM-SCC5, UM-SCC6, and FaDu human head and neck
      cancer cellular susceptibility to the PARP inhibitor (PARPi) ABT-888 and/or
      radiation (IR) was assessed using colony formation assays. DNA damage was
      evaluated using the alkaline comet assay and immunostaining for gamma-H2AX foci.
      Non-homologous end-joining (NHEJ) mediated repair was measured using phospho-DNA
      Pk foci. Epidermal growth factor receptor (EGFR) location was assessed by
      immunostaining. Poly ADP-Ribose polymerization (PAR) levels were assessed using
      immunoblotting. RESULTS: Human head and neck cancer cells exhibited enhanced
      cytotoxicity with IR and ABT-888 compared to either agent alone. This increased
      susceptibility correlated with reduced nuclear EGFR, attenuation of NHEJ, and
      persistence of DNA damage following IR. Interestingly, a subset of head and neck
      cancer cells which had elevated basal PAR levels was susceptible to PARPi alone.
      CONCLUSIONS: Combining radiotherapy and PARP inhibition may improve outcomes and
      quality of life for head and neck cancer patients treated with radiotherapy.
      Furthermore, this novel strategy may also be feasible in other tumor types.
      Moreover, PAR levels should be investigated as a potential biomarker for tumor
      susceptibility to PARP inhibition.

PMID- 21719138
TI  - High hydrostatic pressure processing reduces Salmonella enterica serovars in
      diced and whole tomatoes.
AB  - Fresh and fresh-cut tomatoes have been associated with numerous outbreaks of
      salmonellosis in recent years. One effective post harvest treatment to reduce
      Salmonella enterica in tomatoes may be high pressure processing (HPP). The
      objectives of the study were to determine the potential for HPP to reduce S.
      enterica serovars Newport, Javiana, Braenderup and Anatum in tryptic soy broth
      (TSB) and to determine the effect of HPP to reduce the most pressure resistant of
      the four serovars from fresh diced and whole tomatoes. To evaluate pressure
      resistance, TSB containing 8 log CFU/ml of one of the four serovars was packaged
      in sterile stomacher bags and subjected to one of three different pressures (350,
      450 or 550MPa) for 120s. The most pressure resistant S. enterica serovar
      evaluated was Braenderup. Subjecting the broth culture to 350, 450 and 550MPa
      resulted in a 4.53, 5.74 and 7.09 log reduction in S. Braenderup, respectively.
      Diced tomatoes (150g) and whole red round tomatoes (approximately 150g) were
      inoculated with 0.1ml of 9.1 log CFU/ml S. Braenderup, and subjected to the same
      pressure treatments (350, 450 or 550MPa). Significant reductions of S. Braenderup
      concentrations in diced tomatoes (P<0.05) were seen after processing at 350
      (0.46CFU/g), 450 (1.44 log CFU/g), and 550MPa (3.67 log CFU/g). In whole
      tomatoes, significant reductions (P<0.05) were also seen at 350 (1.41 log CFU/g),
      450 (2.25 log CFU/g) and 550MPa (3.35 log CFU/g). HPP may be an effective post
      harvest strategy to reduce low levels of S. enterica contamination in whole and
      diced tomatoes.

PMID- 21719139
TI  - A new model for 5-year risk of cardiovascular disease in type 2 diabetes, from
      the Swedish National Diabetes Register (NDR).
AB  - AIM: We assessed the association between risk factors and cardiovascular disease
      (CVD) in an observational study of type 2 diabetes patients from the Swedish
      National Diabetes Register. METHODS: A derivation sample of 24,288 patients, aged
      30-74 years, 15.3% with previous CVD, baseline 2002, 2488 CVD events when
      followed for 5 years until 2007. A separate validation data set of 4906 patients,
      baseline 2003, 522 CVD events when followed for 4 years. RESULTS: Adjusted hazard
      ratios at Cox regression for fatal/nonfatal CVD were: onset-age 1.59, diabetes
      duration 1.55, total-cholesterol-to-HDL-cholesterol ratio 1.20, HbA1c 1.12,
      systolic BP 1.09, BMI 1.07 (1 SD increase in natural log continuous variables);
      males 1.41, smoker 1.35, microalbuminuria 1.27, macroalbuminuria 1.53, atrial
      fibrillation 1.50, previous CVD 1.98 (all p<0.001 except BMI p=0.0018). All 12
      variables were used to elaborate an equation for 5-year CVD risk in the
      derivation dataset: mean 5-year risk 11.9+/-8.4%. Calibration in the validation
      dataset was adequate: ratio predicted 4-year risk/observed rate 0.97.
      Discrimination was sufficient: C statistic 0.72, sensitivity 51% and specificity
      78% for top quartile. CONCLUSION: This CVD risk model from a large observational
      study of patients in routine care showed adequate calibration and discrimination,
      and can be useful for clinical practice.

PMID- 21719140
TI  - Implementing changes to hospital services: factors influencing the process and
      'results' of reconfiguration.
AB  - OBJECTIVES: Acute hospital reconfiguration is often presented as a problem to be
      solved by calculations of optimal design, a rational process amenable to
      influence by open and responsive consultation. We aimed to analyse factors in the
      process and 'results' of hospital reconfiguration in three case study sites in
      the English NHS. METHODS: In-depth semi-structured interviews were conducted with
      internal and external stakeholders at each site. Analysis within each case was
      complemented by cross-case analysis focusing on the relationships between the
      features of the origins and process of reconfiguration and progress in the
      implementation of plans. FINDINGS: We identified a number of inter-related
      factors operating in the process of implementation which influenced the
      'results': the drivers for change, the reconfiguration, its content (particularly
      the extent to which services are withdrawn or made less accessible), the
      influence of stakeholders, such as local politicians, financial pressures, and
      the role of the management team. CONCLUSIONS: We argue that the differences in
      reconfiguration implementation between the three cases reflected the nature of
      the proposed changes and local politics, rather than the strength of the
      'evidence' for change. National policy has tended to over-emphasise the
      importance of consultation using 'evidence' and underplays these influencing
      factors.

PMID- 21719141
TI  - An eikonal-diffusion solver and its application to the interpolation and the
      simulation of reentrant cardiac activations.
AB  - Electrical propagation of the cardiac impulse in the myocardium can be described
      by the eikonal-diffusion equation. This equation governs the field of activation
      times in a domain where conduction properties are specified. This approach has
      been applied to knowledge-based interpolation of sparse measurements of
      activation times and to the creation of initial conditions for detailed ionic
      models of cardiac propagation. This paper presents the mathematical basis, matrix
      formulation, and compact Matlab implementation of an iterative finite-element
      solver (triangular meshes) for the eikonal-diffusion equation extended to
      reentrant activations, which automatically identifies the period of reentry and
      computes the resulting isochrones. An iterative algorithm is designed to perform
      Laplacian interpolation of reentrant activation maps to be used as initial
      estimate for the eikonal-diffusion solver. The performance of the algorithm is
      analyzed in test-case geometries (ventricular slice and simplified atrial surface
      model).

PMID- 21719142
TI  - Prognostic potential of FOXP3 expression in non-small cell lung cancer cells
      combined with tumor-infiltrating regulatory T cells.
AB  - Expression of the transcription factor FOXP3 characterizes regulatory T cells
      (Tregs) that engage in the maintenance of immunological self-tolerance and immune
      homeostasis. Intra-tumoral accumulation of Tregs is associated with unfavorable
      prognosis in several kinds of cancers. Recently, expression of FOXP3 and its
      association with prognosis have also been shown in some cancer cells in clinical
      studies. For non-small cell lung cancer (NSCLC), however, prognostic significance
      of tumor FOXP3 expression and its relationship with Tregs remain unknown. FOXP3
      expression in cancer cells and tumor-infiltrating lymphocytes was examined by
      immunohistochemical staining of surgical specimens from 87 patients with NSCLC.
      Prognostic values of the tumor-infiltrating Treg count and tumor FOXP3 expression
      status were evaluated retrospectively. FOXP3-positive cancer cells were observed
      in 27 of 87 (31.0%) patients. There was no significant relationship between Treg
      count and tumor FOXP3 status. Increased Treg counts were associated with worse
      overall and relapse-free survival whereas the influence of tumor FOXP3 status on
      survival was not significant. However, when FOXP3-positive cancer cells were
      present, the relationship between Treg accumulation and worse prognosis was
      attenuated. In contrast, patients without tumor FOXP3 expression and high Treg
      count had significantly worse overall and relapse-free survival (hazard ratio:
      3.118 and 3.325, p=0.028 and 0.024, respectively) than other groups. These
      results suggest that tumor FOXP3 expression has a better prognostic potential in
      NSCLC and that in combination with tumor-infiltrating Treg count the absence of
      tumor FOXP3 allows the selection of high-risk patients.

PMID- 21719143
TI  - Signet ring cell adenocarcinoma of the lung with an EML4-ALK fusion gene
      mimicking mucinous (colloid) adenocarcinoma: a case report.
AB  - We herein report a case of signet ring cell adenocarcinoma of the lung with an
      EML4-ALK fusion gene mimicking mucinous (colloid) adenocarcinoma. A 79-year-old
      female presented with a pulmonary tumor located in the right lower lobe measuring
      21 mm in size. A right lower lobectomy was performed. The postoperative
      pathological examination revealed signet ring cell carcinoma with abundant mucin
      pools, and a multiplex RT-PCR analysis revealed the variant 2 inversion of the
      EML4-ALK gene.

PMID- 21719145
TI  - Antigen presenting cells in a non-mammalian model system, the chicken.
AB  - The chicken has a different repertoire of tissues, cells and genes of the immune
      response compared to mammals, yet generally survives infection with viral,
      bacterial, protozoal and fungal pathogens, and also worms and ectoparasites, just
      like mammals. Poultry are also probably the most heavily vaccinated group of
      farmed animals. Antigen presentation to the adaptive immune response therefore
      obviously normally occurs efficiently in birds. Although comparatively much is
      known about macrophages and B cells in the chicken, there is as yet little work
      on the other, professional, antigen-presenting cells, the dendritic cells (DC).
      Birds also have at least two other sets of phagocytic cells, heterophils and
      thrombocytes, which may also have the ability to present antigen. Here we review
      the current state of knowledge about antigen presenting cells in the chicken,
      concentrating mainly on recent advances in our knowledge of DC.

PMID- 21719146
TI  - [Detection of keratoconus using wavefront analysis].
AB  - PURPOSE: To determine the value of wavefront analysis in the detection of
      keratoconus. PATIENTS AND METHODS: A prospective study was conducted from May
      2008 to May 2010. Four groups were formed: patients with a "healthy" cornea
      (group 0; n=48), patients with keratoconus "suspect" (group 1; n=43), patients
      with keratoconus "forme fruste" (group 2; n=31), and patients with "beginning"
      keratoconus (group 3; n=47). Total and corneal aberrations were analysed. The
      Fisher test and Student t-test were used to compare the different groups.
      Receiver operating characteristic (ROC) curves were plotted when aberration
      differentiated groups 0 and 1. RESULTS: Total and corneal coma (Z 3), the corneal
      trefoil, (Z 3) and the corneal secondary astigmatism (Z 4) differentiated groups
      0 and 1. Sensitivities and specificities of total and corneal coma, corneal
      trefoil, and corneal secondary astigmatism were, respectively, 67.4%, 56.3%
      (Youden=0.237), 60.5%, 72.9% (Youden=0.334), 83.7%, 39.6% (Youden=0.233), and
      65.1%, 58.3% (Youden=0.234). Total, corneal coma, and corneal trefoil
      differentiated all severity groups. The third high-order aberrations
      differentiated groups 1 and 2. DISCUSSION: High-order aberrations are good
      indicators for grading keratoconus. Total high-order aberrations are less
      discriminating than corneal high-order aberrations. Corneal coma (Z 3) is the
      most discriminating aberration to differentiate the healthy cornea from the
      suspect cornea. Nevertheless, it does not optimally detect keratoconus suspect
      (Youden=0.334 and sensitivity=60.5%). The statistical analysis suggests that
      keratoconus suspect and forme fruste are different entities. CONCLUSION:
      Wavefront analysis can be used for the detection of keratoconus suspect, forme
      fruste, and beginning keratoconus but must be associated with videotopography and
      pachymetry during consultation of refractive surgery.

PMID- 21719147
TI  - [Recurrence of an idiopathic vasocentric epiretinal membrane: clinical and
      surgical particularities].
AB  - The vasocentric epiretinal membranes (ERM) are idiopathic ERM centered on retinal
      blood vessels, described mainly in young patients. We report a case of a 70-year
      old patient who presented with a decrease in visual acuity secondary to a
      vasocentric epiretinal membrane. A successful vitrectomy and ERM removal were
      performed. Four years after surgery, a contractile ERM centered on the superior
      temporal blood vessel occurred and was associated with retinal distortions at the
      posterior pole. The second surgery combined removal of the recurrent ERM, which
      was adherent to the temporal vessels, and peeling of the internal limiting
      membrane in the macular area. Although there was visual recovery, the patient is
      still suffering from metamorphopsia 2 years after surgery. The vasocentric ERM
      have a poor visual outcome and a high risk of recurrence in comparison with other
      ERM disorders. This case report describes the main clinical and surgical
      characteristics of this type of membrane.

PMID- 21719148
TI  - Is pre-emptive strict isolation of patients at high risk of colonization with
      MRSA still required in low-prevalence countries?

PMID- 21719149
TI  - Guidelines for infection control in nursing homes: a Delphi consensus web-based
      survey.
AB  - A nationwide survey was performed using a two-round web-based Delphi procedure to
      develop a set of consensus guidelines for preventing infections among residents
      in nursing homes (NHs). The research group was led by an investigative group of
      six specialists. Research analysts conducted a literature search and review of
      practice guidelines, systematic reviews and articles or abstracts published in
      English and French on the topic of infection prevention. The literature search
      was examined by 23 specialists (who compiled a preliminary list of 301
      recommendations). Using a Delphi survey online instrument, 81 experts from all
      relevant medical specialties in the fields of infection prevention and control
      and geriatrics rated their agreement with each of the recommendations using a
      nine-point scale (1 = strongly disagree, 9 = strongly agree). During the second
      round, 79 participants received anonymous feedback from the first round and
      assessed a narrowed list of 130 recommendations. Recommendations were retained
      and classified according to the overall median score and ratings percentages by
      stakeholders. A total of 79 raters rated >= 10% of items, and 264 recommendations
      were retained and rated as follows: 240 items reached consensus, 24 items reached
      near consensus, 37 items were discarded and one recommendation was deleted. Many
      infections, though not all, can be prevented in the frail elderly. Thus, these
      guidelines should be adopted by each healthcare professional and facility to
      implement routine infection control procedures.

PMID- 21719150
TI  - Effectiveness of oral hygiene interventions against oral and oropharyngeal
      reservoirs of aerobic and facultatively anaerobic gram-negative bacilli.
AB  - BACKGROUND: Aerobic and facultatively anaerobic gram-negative bacilli (AGNB) are
      opportunistic pathogens and continue to cause a large number of hospital-acquired
      infections. AGNB residing in the oral cavity and oropharynx have been linked to
      nosocomial pneumonia and septicemia. Although AGNB are not considered members of
      the normal oral and oropharyngeal flora, medically compromised patients have been
      demonstrated to be susceptible to AGNB colonization. METHODS: A literature search
      was conducted to retrieve articles that evaluated the effectiveness of oral
      hygiene interventions in reducing the oral and oropharyngeal carriage of AGNB in
      medically compromised patients. RESULTS: Few studies have documented the use of
      mechanical oral hygiene interventions alone against AGNB. Although a number of
      studies have employed oral hygiene interventions complemented by antiseptic
      agents such as chlorhexidine and povidone iodine, there appears to be a
      discrepancy between their in vitro and in vivo effectiveness. CONCLUSION: With
      the recognition of the oral cavity and oropharynx as a reservoir of AGNB and the
      recent emergence of multidrug and pandrug resistance in hospital settings, there
      is a pressing need for additional high-quality randomized controlled trials to
      determine which oral hygiene interventions or combination of interventions are
      most effective in eliminating or reducing AGNB carriage.

PMID- 21719151
TI  - [Hospital costs associated with delirium in older medical patients].
AB  - INTRODUCTION: Delirium is a common and serious complication in older patients,
      associated with increased, potentially preventable, morbidity and mortality. The
      aim of this study was to evaluate the associated costs of delirium during
      hospitalization in a university affiliated hospital in Chile. MATERIALS AND
      METHODS: Prospective cohort study of consecutive patients 65 years and older,
      admitted to a medical ward. A psychogeriatric team assessed patients during the
      first and every 48h until discharge using the Confusion Assessment Method (CAM
      S), length of hospital stay, pharmacy and total hospitalization costs were
      analyzed. Statistical analysis was performed using bivariate and multivariate
      analysis according to delirium diagnosis. RESULTS: Data from 454 patients was
      analyzed, 160 of them in a delirium cohort (35.2%) and 294 in a non-delirium
      cohort (64.8%). The delirium cohort had a longer hospital stay (DATA) and higher
      mortality (7.0% versus 1.7%). The median of total costs of delirium during
      hospital stay was 38.7% higher than the non-delirium cohort (P<.001). Total costs
      were significantly higher in the delirium cohort after adjustment of covariables
      (P=.01). CONCLUSIONS: This study confirms that delirium is associated with
      significantly greater costs. Considering that effective delirium prevention is
      possible, the knowledge of associated costs can help health care providers to
      justify prevention strategies and finally give better care for older patients.

PMID- 21719152
TI  - [Efficiency of acute geriatric units: a meta-analysis of controlled studies].
AB  - OBJECTIVE: After analysing the effectiveness in the reduction in the incidence of
      functional impairment and a higher probability of returning home between elderly
      patients hospitalised due to an acute medical illness cared for in acute
      geriatric units (AGU) compared to conventional care units, we propose to assess
      the efficiency of this care. MATERIAL AND METHODS: A systematic review and meta
      analysis was made of controlled studies (randomised, no randomised and case
      control) that compared care in UGA with care in conventional hospital units of
      patients of 65 years and over with an acute medical illness. Studies on
      administrative data bases, those that evaluated care of a single disease, and
      those that assessed units with care in the acute and sub-acute phase were
      excluded. A literature review was performed on articles published up to 31st of
      August 2008 in Medline, Embase, Cochrane Library, and references of systematic
      reviews and reviewed articles. The selection of the studies and the extraction of
      data on the hospital stay and care costs was made independently by two different
      researchers. RESULTS: A total of 11 studies were included, of which 5 were
      randomised, 4 were non-randomised, and 2 case control, all of them providing data
      on hospital stay, with 7 of them providing data on hospital costs (4 clinical
      trials, 2 non-randomised and 1 case-control). The overall analysis of all the
      studies showed that those admitted to UGA had a statistically significant
      reduction in hospital length of stay compared to the elderly hospitalised in
      conventional units (mean difference -1.01 days; 95% CI, -1.66 to -0.36) and
      hospital care costs (mean difference of -330 US dollars; 95% CI, -540 to -120).
      CONCLUSIONS: Care in AGU is more efficient than that provided in conventional
      units, since, as well as achieving a reduction in the incidence of functional
      impairment at discharge and increasing the probability of returning home, they
      reduce mean hospital stay and the hospital care costs.

PMID- 21719153
TI  - [The short stay unit as an alternative to conventional hospitalisation in the
      treatment of community acquired pneumonia in the over 75 year-old population].
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) is a major cause of morbidity
      and mortality in elderly patients. The short stay units can be an alternative for
      patients who need admission with acute illness. MATERIAL AND METHODS: Descriptive
      and retrospective study in an Short-Stay Unit (SSU) of a 900-bed tertiary-care
      teaching hospital in the metropolitan area of Barcelona, Spain. PERIOD: a total
      of 22 months from January 2004 to December 2006. PATIENTS: all patients >= 75
      years admitted to EDSSU with a diagnosis of CAP. Data were collected for
      demographic variables, Pneumonia Severity Index score (PSI), microbiological
      findings, antibiotic treatment, length of stay, mortality rates and new
      admissions during the 30 days following discharge. RESULTS: 175 consecutive
      patients >= 75 years with pneumonia were admitted to the EDSSU. Mean age was
      84.31 years (range 75-100, SD +/- 5.76), 92 (52,5%) were men, with 24 being
      nursing home residents. According to the PSI, 64 cases (36.6%) were scored as
      III, 97 (55.4%) as IV and 14 (8%) as V. A positive microbiological result was
      obtained in 46 cases (26.2%). Length of stay on average was 3.29 days (range 1
      10, SD +/- 1.56) and 19 patients died (10.8%). Six (3.8%) attended the ED in the
      30 days following discharge. CONCLUSIONS: In view of our experience, the EDSSU
      can be an alternative to standard inpatient for elderly patients with pneumonia
      in PSI risk class III and IV.

PMID- 21719154
TI  - [Private medical insurance].

PMID- 21719155
TI  - [What can we do about the long-term use of bisphosphonates? Fractures and atrial
      fibrillation].

PMID- 21719156
TI  - [Normal data of functional assessment tools of the elderly in Spain: the FRADEA
      study].
AB  - OBJECTIVE: To determine the normal values of some of the functional assessment
      tools most used in Spain. DESIGN: Cross-sectional study of the first cut of a
      concurrent population based cohort. SETTING: Albacete city Health Area.
      PARTICIPANTS: A total of 993 subjects aged 70 years or over and participants in
      the FRADEA (Frailty and dependence in Albacete, Spain) cohort. MAIN MEASUREMENTS:
      An analysis was made of disability and function questionnaires, which included,
      Barthel, Lawton and Short Form of the Late-Life Function and Disability
      Instrument (SF-LLFDI), Holden's Functional Ambulation Category (FAC), and
      functional tests: walking speed (m/s), Timed Up and Go (TUG) (sec), one-leg
      balance time (sec), timed 5 Times Sit to Stand Test (5STS) (seg), Short Physical
      Performance Battery (SPPB), grip strength (kg), and elbow flexion strength (kg).
      The means, quartiles and percentiles are described, in the global cohort and in
      the male and female sub-groups aged between 70 and 79 years or aged 80 years or
      over. RESULTS: The quartiles of the different instruments were as follow: Barthel
      (80, 95, 100), Lawton (3, 6,8), SF-LLFDI (70, 111, 131), FAC (4, 5, 5), walking
      speed (0.51, 0.79, 1.00), TUG (13.8, 11.4, 9.8), one-leg balance time (3, 7, 15),
      5STS (16.3, 13.0, 10.7), SPPB (7, 9, 11), grip strength (15, 20, 29), and elbow
      flexion strength (11, 20, 32). The younger ones, males and those living within
      the community showed a better performance in all the instruments. CONCLUSIONS:
      The normal values of a cohort of the elderly population based in Albacete using
      different functional assessment instruments are presented. These could be useful
      in clinical practice or research.

PMID- 21719157
TI  - [Comments on living wills].

PMID- 21719158
TI  - Supraclavicular metastasis in prostate cancer detected with 18F-fluorocholine
      PET/CT.

PMID- 21719159
TI  - Frontal meningioma on 99mTc-MIBI scan for postoperative evaluation of
      differentiated thyroid cancer.

PMID- 21719160
TI  - [Barriers to the normalization of telemedicine in a healthcare system model based
      on purchasing of healthcare services using providers' contracts].
AB  - OBJECTIVE: Despite the clear political will to promote telemedicine and the large
      number of initiatives, the incorporation of this modality in clinical practice
      remains limited. The objective of this study was to identify the barriers
      perceived by key professionals who actively participate in the design and
      implementation of telemedicine in a healthcare system model based on purchasing
      of healthcare services using providers' contracts. METHODS: We performed a
      qualitative study based on data from semi-structured interviews with 17 key
      informants belonging to distinct Catalan health organizations. RESULTS: The
      barriers identified were grouped in four areas: technological, organizational,
      human and economic. The main barriers identified were changes in the healthcare
      model caused by telemedicine, problems with strategic alignment, resistance to
      change in the (re)definition of roles, responsibilities and new skills, and lack
      of a business model that incorporates telemedicine in the services portfolio to
      ensure its sustainability. CONCLUSIONS: In addition to suitable management of
      change and of the necessary strategic alignment, the definitive normalization of
      telemedicine in a mixed healthcare model based on purchasing of healthcare
      services using providers' contracts requires a clear and stable business model
      that incorporates this modality in the services portfolio and allows healthcare
      organizations to obtain reimbursement from the payer.

PMID- 21719161
TI  - [Death, dignity and advance directives].

PMID- 21719162
TI  - Synthesis of novel 1,2,5-trisubstituted benzimidazoles as potential antitumor
      agents.
AB  - Novel methyl 1-(5-tert-butyl-1H-pyrazol-3-yl)-2-(aryl)-1H-benzo[d]imidazole-5
      carboxylates 11 were synthesized by following a four-step strategy involving a
      nucleophilic aromatic displacement (S(N)Ar) and a solvent free approach as key
      steps for the formation of the desired products. Structure of intermediates and
      products were confirmed by X-ray diffraction as well as the tautomeric
      rearrangement suffered by the pyrazole moiety during the curse of the final
      cyclization process. Several of the obtained compounds were screened by the US
      National Cancer Institute (NCI) for their ability to inhibit 60 different human
      tumor cell lines. Products 11b and 11n exhibited the highest activity against a
      range of cancer cell lines with remarkable values in panels of Non-Small Cell
      Lung Cancer, Melanoma and Leukemia, with GI(50) range of 1.15-7.33 MUM and 0.167
      7.59 MUM, respectively, and suitable LC(50) with values greater than 100 MUM.

PMID- 21719163
TI  - A chrysin analog exhibited strong inhibitory activities against both PGE2 and NO
      production.
AB  - A number of 8-substituted chrysin analogs have been prepared and evaluated for
      their inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin E(2) and
      iNOS-mediated NO production. Analogs were prepared via Suzuki-Miyaura C-C cross
      coupling reaction of 8-iodo-5,7-dimethoxyflavone and alkyl/areneboronic acids as
      a key reaction. Among the analogs tested, 5,7-dihydroxy-8-(pyridine-4-yl)flavone
      (3d) showed strong biological activities against COX-2 catalyzed PGE(2) and iNOS
      mediated NO production from LPS-induced RAW 264.7 cells compared to those of
      chrysin.

PMID- 21719164
TI  - Aminothiophenedicarboxamides and dicyanothiopheneacetamides as effective
      synthetic molluscicides against Indoplanorbis exustus snail.
AB  - New thiophenedicarboxamide 2a-c and dicyanothiopheneacetamide 3a-c derivatives
      were synthesized and their bioactivity against Indoplanorbis exustus snails was
      evaluated. The I. exustus snail is a serious host of parasite of genus
      Schistosoma which infects cattle. Thus reduces livestock productivity and also
      acts as a source of cercarial dermatitis in human beings. The results obtained
      show a significant (P < 0.05) molluscicidal activity with LC(50) = 0.6043 ppm for
      compound 2a and LC(50) = 0.6511 ppm for compound 3a.

PMID- 21719165
TI  - Reducing glucose infusion safely prevents hyperglycemia in post-surgical
      children.
AB  - BACKGROUND & AIMS: To investigate the effects of two different glucose infusions
      on glucose homeostasis and amino acid metabolism in post-surgical children.
      METHODS: This randomized crossover study evaluated glucose and amino acid
      metabolism in eight children (age 9.8 +/- 1.9 months, weight 9.5 +/- 1.1 kg)
      admitted to a pediatric intensive care unit in a tertiary university hospital
      after surgical correction for non-syndromal craniosynostosis. Patients were
      randomized to receive low (LG; 2.5 mg kg(-1) min(-1)) and standard (SG; 5.0 mg
      kg(-1) min(-1)) glucose infusion in a crossover setting. After a bolus (4 g kg(
      1)) of deuterium oxide, we conducted a primed, constant, 8 h tracer infusion with
      [6,6-2H2]Glucose, [1-13C]Leucine, [ring-2H5]Phenylalanine and [3,3-2H2]Tyrosine.
      RESULTS: SG resulted in hyperglycemia (defined as > 6.1 mmol L(-1)), while during
      LG plasma glucose levels were normoglycemic (5.9 +/- 0.6 vs. 7.5 +/- 1.7 mmol L(
      1); LG vs. SG respectively, p = 0.02). Hypoglycemia did not occur during LG
      infusion. Endogenous glucose production was not fully suppressed during the
      hyperglycemic state under SG and increased with reduced glucose infusion (2.6 +/-
      1.5 vs. 1.1 +/- 1.4 mg kg(-1) min(-1); LG vs. SG; p = 0.05). Whole body protein
      balance derived from leucine and phenylalanine kinetics was slightly negative but
      not further affected with a decrease in glucose infusion. CONCLUSIONS: The
      current recommended glucose infusion induces hyperglycemia in post-surgical
      children. A reduced glucose infusion safely reduced high glucose levels, while
      children were capable to sustain normoglycemia with increased endogenous glucose
      production. The reduced glucose infusion did not exacerbate the mild catabolic
      state in which the patients were.

PMID- 21719166
TI  - Temporal changes of 7Be, 137Cs and 210Pb activity concentrations in surface air
      at Monaco and their correlation with meteorological parameters.
AB  - Results of analysis of (7)Be, (137)Cs and (210)Pb on aerosol filters carried out
      from 1998 to 2010 in Monaco show that a weak correlation between activity
      concentrations of these radionuclides in the atmosphere and meteorological
      parameters has been found for (7)Be and temperature (r = 0.50), (210)Pb and
      temperature and humidity (r = 0.43 and 0.41, respectively), and (137)Cs and
      precipitation (r = 0.51). The minimum and maximum (7)Be activity concentrations
      were observed during 2000 and 2009, corresponding with the maximum and minimum
      solar activity, respectively. The maximum (137)Cs activity concentration found in
      May-June 1998 was due to the accident at Algeciras in Spain. The deposition
      velocities of (7)Be, (137)Cs and (210)Pb depended on the precipitation rate, and
      attained maximum values during dry seasons. The investigated radionuclides may be
      used as atmospheric tracers, especially in long-term periods.

PMID- 21719167
TI  - Arrival time and magnitude of airborne fission products from the Fukushima,
      Japan, reactor incident as measured in Seattle, WA, USA.
AB  - We report results of air monitoring started due to the recent natural catastrophe
      on 11 March 2011 in Japan and the severe ensuing damage to the Fukushima Dai-ichi
      nuclear reactor complex. On 17-18 March 2011, we registered the first arrival of
      the airborne fission products (131)I, (132)I, (132)Te, (134)Cs, and (137)Cs in
      Seattle, WA, USA, by identifying their characteristic gamma rays using a
      germanium detector. We measured the evolution of the activities over a period of
      23 days at the end of which the activities had mostly fallen below our detection
      limit. The highest detected activity from radionuclides attached to particulate
      matter amounted to 4.4 +/- 1.3 mBq m(-3) of (131)I on 19-20 March.

PMID- 21719168
TI  - Measurement of shoulder joint loads during wheelchair propulsion measured in
      vivo.
AB  - BACKGROUND: Recent in vivo measurements show that the loads acting in the
      glenohumeral joint are high even during activities of daily living. Wheelchair
      users are frequently affected by shoulder problems. With previous musculoskeletal
      shoulder models, shoulder joint loading was mostly calculated during well-defined
      activities like forward flexion or abduction. For complex movements of everyday
      living or wheelchair propulsion, the reported loads vary considerably. METHODS:
      Shoulder joint forces and moments were measured with telemeterized implants in 6
      subjects. Data were captured on a treadmill at defined speeds and inclinations.
      Additional measurements were taken in 1 subject when lifting the body from the
      wheelchair, using his arms only, and in 2 subjects when rapidly accelerating and
      stopping the wheelchair. The influence of the floor material on shoulder joint
      loading was accessed in 2 subjects. In general, the maximum shoulder loads did
      not exceed those during daily living but the time courses and magnitudes of the
      loads intra-individually varied much. FINDINGS: The highest forces acted during
      maximum acceleration and lifting from the wheelchair (128% and 188% of body
      weight). Grass was the only surface which led to a general load increase,
      compared to a smooth floor. INTERPRETATION: The increased incidence of overuse
      injuries in wheelchair users are probably not caused by excessive load magnitudes
      during regular propulsion. The high number of repetitions is assumed to be more
      decisive.

PMID- 21719169
TI  - Ageing and limb dominance effects on foot-ground clearance during treadmill and
      overground walking.
AB  - BACKGROUND: Foot-ground clearance during the gait cycle swing phase is a critical
      locomotor adaptation to uneven terrain and non-optimal lower limb control has
      been linked to tripping and falling. The aim of this research was to determine
      ageing effects on bilateral foot-ground clearance during overground and treadmill
      walking. METHODS: Ageing and walking surface effects on bilateral foot trajectory
      control were investigated in 11 older (mean age 73.8 years) and 11 young (mean
      age 22.5 years) participants. First maximum clearance after toe-off, minimum foot
      ground clearance and second maximum clearance prior to heel contact were
      determined from sampled 3-dimensional marker coordinates during preferred-speed
      treadmill walking and walking overground. FINDINGS: Preferred walking speed was
      lower in treadmill walking for both groups. In both groups non-dominant minimum
      foot-ground clearance and first maximum clearance were greater than for the
      dominant foot. A high positive correlation was found between these two swing foot
      clearances when older adults walked on the treadmill. Second maximum clearance
      was reduced in the older group but this was the only overall age effect.
      Treadmill walking reduced minimum foot-ground clearance relative to overground
      locomotion except in the older adults' non-dominant limb that revealed greater
      vertical clearance height in the non-dominant foot. INTERPRETATION: Decreased
      second maximum clearance in the older group may be linked to reduced
      dorsiflexion. Greater minimum foot-ground clearance in the older adults' non
      dominant foot may reflect functional asymmetry, in which the non-dominant limb
      primarily secures or stabilizes gait. The high positive correlation between first
      maximum and minimum foot-ground clearances suggests that intervention designed to
      increase first maximum clearance may also increase minimum foot-ground clearance.
      A direction for future research is to further understand ageing effects on lower
      limb trajectory variables in response to a range of walking surface
      characteristics.

PMID- 21719170
TI  - A synthesis of rates and controls on elemental mercury evasion in the Great Lakes
      Basin.
AB  - Rates of surface-air elemental mercury (Hg(0)) fluxes in the literature were
      synthesized for the Great Lakes Basin (GLB). For the majority of surfaces, fluxes
      were net positive (evasion). Digital land-cover data were combined with
      representative evasion rates and used to estimate annual Hg(0) evasion for the
      GLB (7.7 Mg/yr). This value is less than our estimate of total Hg deposition to
      the area (15.9 Mg/yr), suggesting the GLB is a net sink for atmospheric Hg. The
      greatest contributors to annual evasion for the basin are agricultural (~55%) and
      forest (~25%) land cover types, and the open water of the Great Lakes (~15%).
      Areal evasion rates were similar across most land cover types (range: 7.0-21.0
      MUg/m(2)-yr), with higher rates associated with urban (12.6 MUg/m(2)-yr) and
      agricultural (21.0 MUg/m(2)-yr) lands. Uncertainty in these estimates could be
      partially remedied through a unified methodological approach to estimating Hg(0)
      fluxes.

PMID- 21719171
TI  - Sorption of simazine to corn straw biochars prepared at different pyrolytic
      temperatures.
AB  - Simazine sorption to corn straw biochars prepared at various temperatures (100
      600  degrees C) was examined to understand its sorption behavior as influenced by
      characteristics of biochars. Biochars were characterized via elemental analysis,
      BET-N(2) surface area (SA), FTIR and (13)C NMR. Freundlich and dual-mode models
      described sorption isotherms well. Positive correlation between log K(oc) values
      and aromatic C contents and negative correlation between log K(oc) values and (O
      + N)/C ratios indicate aromatic-rich biochars have high binding affinity to
      simazine (charge transfer (pi-pi*) interactions) and hydrophobic binding may
      overwhelm H-bonding, respectively. Dual-mode model results suggest adsorption
      contribution to total sorption increases with carbonization degree. Positive
      correlation between amounts of adsorption (Q(ad)) and SA indicates pore-filling
      mechanism. Comparison between our results and those obtained with other sorbents
      indicates corn straw biochars produced at higher temperature can effectively
      retain simazine. These observations will be helpful for designing biochars as
      engineered sorbents to remove triazine herbicides.

PMID- 21719172
TI  - Sediment-associated aliphatic and aromatic hydrocarbons in coastal British
      Columbia, Canada: concentrations, composition, and associated risks to protected
      sea otters.
AB  - Sediment-associated hydrocarbons can pose a risk to wildlife that rely on benthic
      marine food webs. We measured hydrocarbons in sediments from the habitat of
      protected sea otters in coastal British Columbia, Canada. Alkane concentrations
      were dominated by higher odd-chain n-alkanes at all sites, indicating terrestrial
      plant inputs. While remote sites were dominated by petrogenic polycyclic aromatic
      hydrocarbons (PAHs), small harbour sites within sea otter habitat and sites from
      an urban reference area reflected weathered petroleum and biomass and fossil fuel
      combustion. The partitioning of hydrocarbons between sediments and adjacent food
      webs provides an important exposure route for sea otters, as they consume ~25% of
      their body weight per day in benthic invertebrates. Thus, exceedences of PAH
      sediment quality guidelines designed to protect aquatic biota at 20% of the sites
      in sea otter habitat suggest that sea otters are vulnerable to hydrocarbon
      contamination even in the absence of catastrophic oil spills.

PMID- 21719173
TI  - Medial fibrosis, vascular calcification, intimal hyperplasia, and arteriovenous
      fistula maturation.
AB  - BACKGROUND: Arteriovenous fistulas (AVFs) for hemodialysis frequently fail to
      mature because of inadequate dilation or early stenosis. The pathogenesis of AVF
      nonmaturation may be related to pre-existing vascular pathologic states: medial
      fibrosis or microcalcification may limit arterial dilation, and intimal
      hyperplasia may cause stenosis. STUDY DESIGN: Observational study. SETTING &
      PARTICIPANTS: Patients with chronic kidney disease (N = 50) undergoing AVF
      placement. PREDICTORS: Medial fibrosis, microcalcification, and intimal
      hyperplasia in arteries and veins obtained during AVF creation. OUTCOME &
      MEASUREMENTS: AVF nonmaturation. RESULTS: AVF nonmaturation occurred in 38% of
      patients despite attempted salvage procedures. Preoperative arterial diameter was
      associated with upper-arm AVF maturation (P = 0.007). Medial fibrosis was similar
      in patients with nonmaturing and mature AVFs (60% +/- 14% vs 66% +/- 13%; P =
      0.2). AVF nonmaturation was not associated with patient age or diabetes, although
      both variables were associated significantly with severe medial fibrosis.
      Conversely, AVF nonmaturation was higher in women than men despite similar medial
      fibrosis in both sexes. Arterial microcalcification (assessed semiquantitatively)
      tended to be associated with AVF nonmaturation (1.3 +/- 0.8 vs 0.9 +/- 0.8; P =
      0.08). None of the arteries or veins obtained at AVF creation had intimal
      hyperplasia. However, repeated venous samples obtained in 6 patients during
      surgical revision of an immature AVF showed venous neointimal hyperplasia.
      LIMITATIONS: Single-center study. CONCLUSION: Medial fibrosis and
      microcalcification are frequent in arteries used to create AVFs, but do not
      explain AVF nonmaturation. Unlike previous studies, intimal hyperplasia was not
      present at baseline, but developed de novo in nonmaturing AVFs.

PMID- 21719174
TI  - Podocytopathy in diabetes: a metabolic and endocrine disorder.
AB  - Diabetic nephropathy (DN) represents a major public health cost. Tight glycemic
      and blood pressure control can dramatically slow, but not stop, the progression
      of the disease, and a large number of patients progress toward end-stage renal
      disease despite currently available interventions. An early and key event in the
      development of DN is loss of podocyte function (or glomerular visceral epithelial
      cells) from the kidney glomerulus, where they contribute to the integrity of the
      glomerular filtration barrier. Recent evidence suggests that podocytes can be the
      direct target of circulating hormones, lipids, and adipokines that are affected
      in diabetes. We review the clinical and experimental evidence implicating novel
      endocrine and metabolic pathways in the pathogenesis of podocyte dysfunction and
      the development of DN.

PMID- 21719175
TI  - Association of PKD2 (polycystin 2) mutations with left-right laterality defects.
AB  - Mutations in the PKD1 (polycystin 1) and PKD2 (polycystin 2) genes cause
      autosomal dominant polycystic kidney disease (ADPKD). Most Pkd2-null mouse
      embryos present with left-right laterality defects. For the first time, we report
      the association of ADPKD resulting from a mutation in PKD2 and left-right
      asymmetry defects. PKD1 and PKD2 were screened for mutations or large genomic
      rearrangements in 3 unrelated patients with ADPKD presenting with laterality
      defects: dextrocardia in one and situs inversus totalis in 2 others. A large gene
      deletion, a single-exon duplication, and an in-frame duplication respectively,
      were found in the 3 patients. These polymorphisms were found in all tested
      relatives with ADPKD, but were absent in unaffected related individuals. No left
      right anomalies were found in other members of the 3 families. A possible
      association between heterotaxia and a PKD2 mutation in our 3 patients is
      suggested by: (1) the existence of laterality defects in Pkd2-null mouse and
      zebrafish models and (2) detection of a pathogenic PKD2 mutation in the 3
      probands, although PKD2 mutations account for only 15% of ADPKD families. The
      presence of left-right laterality defects should be systematically screened in
      larger cohorts of patients with ADPKD harboring PKD2 mutations.

PMID- 21719176
TI  - Socioeconomic status and reduced kidney function in the Whitehall II Study: role
      of obesity and metabolic syndrome.
AB  - BACKGROUND: Previous US-based studies have found that chronic kidney disease
      (CKD) disproportionately affects those of more adverse social circumstances. Our
      aim was to show the association between socioeconomic status (SES) and decreased
      kidney function in a European context and explore the role of obesity and
      metabolic syndrome. We consider the potential confounding effect of lean muscle
      mass. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: White participants
      in the follow-up of the Whitehall II cohort: UK-based European population (age,
      55-79 years; n = 5,533), of whom 4,066 men (73%) and 1,467 women (27%) with
      complete data were analyzed. PREDICTORS: Self-reported occupational grade/salary
      range. OUTCOMES: Estimated glomerular filtration rate (GFR) using the CKD-EPI
      (CKD Epidemiology Collaboration) equation. MEASUREMENTS: Body mass index (BMI),
      serum lipid levels, blood pressure, Tanita TBF-300 body composition analyzer,
      impedance-derived lean mass index (LMI). RESULTS: Participants in a lower
      compared with higher occupational grade were at increased odds of having
      decreased GFR (age- and sex-adjusted OR, 1.31; 95% CI, 1.12-1.53; P = 0.001).
      Socioeconomic disparity in LMI was evident in women, but not men. After further
      adjustment for BMI and components of metabolic syndrome, the odds of decreased
      GFR in whites with a lower compared with higher occupational grade was attenuated
      by 23.3% (OR, 1.23; 95% CI, 1.06-1.45; P = 0.008). Adjustment for LMI explained
      15% of the association between SES and estimated GFR. LIMITATIONS: Cross
      sectional design, missing data for subset of participants, no urinary data.
      CONCLUSIONS: BMI and components of metabolic syndrome may explain up to a quarter
      of the association between low SES and decreased GFR, suggesting potential
      modifiable factors.

PMID- 21719177
TI  - Prehemodialysis care by dietitians and first-year mortality after initiation of
      hemodialysis.
AB  - BACKGROUND: Since January 2002, Medicare has provided payment for medical
      nutrition therapy for patients with chronic kidney disease. Few patients receive
      dietary counseling before end-stage renal disease onset; whether such counseling
      is associated with improved outcomes is unknown. STUDY DESIGN: Retrospective
      cohort analysis. SETTING & PARTICIPANTS: Patients who initiated hemodialysis
      therapy on June 1, 2005, to May 31, 2007, in the United States for whom
      predialysis dietitian care was reported on the Centers for Medicare & Medicaid
      Services Medical Evidence Report. PREDICTOR: Dietitian care before end-stage
      renal disease onset. OUTCOME: Time to death. MEASUREMENTS: Propensity score for
      dietitian care calculated using logistic regression; Cox regression analysis used
      to compare time to death by predialysis dietitian care overall and stratified by
      tertiles of propensity score, adjusting for baseline characteristics. RESULTS:
      Most patients (88%) received no dietitian care; 9% received dietitian care for 12
      months or less, and 3% received dietitian care for more than 12 months before
      dialysis therapy initiation (total N = 156,440). Predialysis dietitian care was
      associated independently with higher albumin and lower total cholesterol levels
      at dialysis therapy initiation. There was evidence of an independent association
      between predialysis dietitian care for longer than 12 months and decreased
      mortality during the first year on dialysis therapy for the second tertile of
      propensity score. Adjusted mortality HRs were 1.16 (95% CI, 0.44-3.09; P = 0.8),
      0.81 (95% CI, 0.71-0.93; P = 0.002), and 0.93 (95% CI, 0.86-1.01; P = 0.1) in the
      first, second, and third tertiles of propensity score, respectively. LIMITATIONS:
      Information for dietitian care was missing for 18.6% of Medical Evidence Reports
      and has low sensitivity; including only incident dialysis patients precluded
      evaluation of an association between dietitian care and chronic kidney disease
      progression; the observational design allowed the possibility of residual
      confounding. CONCLUSIONS: Our study suggests an independent association between
      predialysis dietitian care for more than 12 months and lower mortality during the
      first year on dialysis therapy.

PMID- 21719178
TI  - Differences in health between Americans and Western Europeans: Effects on
      longevity and public finance.
AB  - In 1975, 50-year-old Americans could expect to live slightly longer than most of
      their Western European counterparts. By 2005, American life expectancy had fallen
      behind that of most Western European countries. We find that this growing
      longevity gap is primarily due to real declines in the health of near-elderly
      Americans, relative to their Western European peers. We use a microsimulation
      approach to project what US longevity would look like, if US health trends
      approximated those in Western Europe. The model implies that differences in
      health can explain most of the growing gap in remaining life expectancy. In
      addition, we quantify the public finance consequences of this deterioration in
      health. The model predicts that gradually moving American cohorts to the health
      status enjoyed by Western Europeans could save up to $1.1 trillion in discounted
      total health expenditures from 2004 to 2050.

PMID- 21719179
TI  - New bone formation in the maxillary sinus using peripheral venous blood alone.
AB  - PURPOSE: The purpose of this study was to evaluate the amount of bone formation
      under a sinus membrane tented with implants and filled with venous blood as a
      graft material. MATERIALS AND METHODS: Fourteen patients (17 sinus augmentations)
      were consecutively treated with sinus floor elevation via the lateral window
      approach. The lateral bony window was created using a piezoelectric saw, and the
      sinus membrane was elevated to make a new compartment. After resorbable blast
      media-surfaced dental implants were placed simultaneously, the collected
      peripheral venous blood was applied to support the sinus membrane over the
      implant apex, and the bony portion of the lateral window was repositioned to seal
      the lateral window. In 6 cases, samples were taken for biopsy at the time of
      second stage surgery. RESULTS: An average of 6.8 months after the sinus
      augmentation, new bone consolidation in the maxillary sinus was observed by
      radiographic and histologic evaluation. Vital bone formation was 38.70% according
      to the histomorphometric data. Of the 31 implants placed, 2 failed. The overall
      implant survival rate was 93.5%. All failures occurred when implants were placed
      into the extraction socket and were associated with poor initial stability.
      CONCLUSION: This study suggests that simultaneous placement of dental implants
      and injection of peripheral venous blood as a graft material appears to be a safe
      alternative procedure for maxillary sinus augmentation.

PMID- 21719180
TI  - [Perforator propeller flap for cutaneous coverage of the knee].
AB  - Previous pedicled techniques for coverage of the knee use muscular flaps and/or
      local fascio-cutaneous flaps limited to rotate until 90 degrees  on their
      cutaneous base. Freestyle perforator flaps match the patient's anatomy to fill a
      defect. Propeller perforator flaps have been used to treat three patients
      presenting with a skin loss over the knee. The surgery is based on the Echo
      Doppler tracing the good perforator vessels around the wound. We performed two
      supero-medial flaps with a self-closing donor site and one supero-lateral flap
      where a graft was needed. All the patients healed in less than six weeks, with
      satisfying functional and esthetical results. We think freestyle perforator flaps
      are a reliable and predictable technique with a low morbidity rate and they are
      well adapted to cover skin defects over the knee.

PMID- 21719181
TI  - Long-term (5 years) effects of bosentan in patients with pulmonary arterial
      hypertension.
AB  - INTRODUCTION AND OBJECTIVES: Bosentan has proven efficacy in pulmonary
      hypertension in the short term. Little is known about its effects beyond 2 to 3
      years. Our objective was to analyze the efficacy and safety of bosentan in the
      long term (5 years) in patients treated in our center. METHODS: This
      retrospective study sequentially analyzed clinical, functional, and laboratory
      parameters in a series of patients treated initially with bosentan as monotherapy
      from 2002 to 2009 in a single hospital. Treatment success was defined as survival
      without clinical worsening that required additional pulmonary vasodilators.
      RESULTS: We included 20 patients (70% women, mean age 46 +/- 14 years, 65%
      congenital heart disease), with a median follow-up of 64 months. One patient
      required withdrawal of bosentan due to adverse effects. At 4 months, significant
      improvements were achieved in hemodynamic, clinical and functional parameters.
      Clinical and functional benefits persisted at 5-year follow-up. Overall 5-year
      survival after beginning bosentan therapy was 95% (84%-100%). Treatment success
      at 1, 2, 3, 4 and 5 years was 95% (84%-100%), 83% (65%-100%), 78% (58%-98%), 61%
      (38%-84%), and 41% (16%-66%), respectively. The group with better outcomes had NT
      proBNP levels at 1 year <400 pg/mL (P=.013). CONCLUSIONS: In our series,
      treatment success with bosentan in monotherapy was maintained in 78% at 3-year
      follow-up and 41% at 5-year follow-up. The group with long-term success showed
      significantly lower NT-proBNP levels at 1-year follow-up. Survival at 5 years in
      our series was 95%.

PMID- 21719182
TI  - Systematic reviews and meta-analysis: scientific rationale and interpretation.
AB  - Systematic reviews represent a specific type of medical research in which the
      units of analysis are the original primary studies. They are essential tools in
      synthesizing available scientific information, increasing the validity of the
      conclusions of primary studies, and identifying areas for future research. They
      are also indispensable for the practice of evidence-based medicine and the
      medical decision-making process. However, conducting high quality systematic
      reviews is not easy and they can sometimes be difficult to interpret. This
      special article presents the rationale for carrying out and interpreting
      systematic reviews and uses a hypothetical example to draw attention to key
      points.

PMID- 21719184
TI  - Measuring adherence among nurses one year after training in applying the Modified
      Early Warning Score and Situation-Background-Assessment-Recommendation
      instruments.
AB  - BACKGROUND: Patients with a cardiac arrest or unplanned intensive care admission
      show gradual decline in clinical condition preceding the event. This can be
      objectified by measuring the vital parameters and subsequently determining the
      Modified Early Warning Score (MEWS). Contact with the physician by nurses may be
      structured using the Situation-Background-Assessment-Recommendation (SBAR)
      communication instrument. The aim of our study was to evaluate whether nurses
      trained in the use of MEWS and SBAR tools were more likely to recognize a
      deteriorating patient. DESIGN AND SETTING: This prospective quasi-experimental
      trial in the Academic Medical Center in Amsterdam, the Netherlands included three
      medical and three surgical wards. INTERVENTIONS: A group of 47 trained and 48 non
      trained nurses were presented with a case of a deteriorating patient, and
      subsequent assessment and actions regarding the patient case were measured.
      RESULTS: Of the trained nurses, 77% versus 58% of the non-trained group assessed
      the patient immediately. On subsequent assessment of the patient, respiratory
      rate was measured twice as frequently (53% trained versus 25% non-trained,
      p=0.025). No differences were found in the measurement of other vital parameters.
      The MEWS was determined by 11% of trained nurses. Subsequent notification of the
      physician was performed by 67% of the trained versus 43% of the non-trained
      nurses. The SBAR communication tool was used by only one nurse. CONCLUSIONS:
      Trained nurses are able to identify a deteriorating patient and react more
      appropriately. However, despite rigorously implementing MEWS/SBAR methodology,
      these tools were rarely used.

PMID- 21719185
TI  - Imaging brain injury after cardiac arrest resuscitation when it really matters.

PMID- 21719186
TI  - Response: "urinary albumin excretion in polycystic ovary syndrome: contributions
      from a study considering low grade albuminuria".

PMID- 21719187
TI  - Association between cytokine gene polymorphisms and cervical cancer in a Chinese
      population.
AB  - OBJECTIVES: It has been hypothesized that inherited cytokine gene polymorphisms
      could influence susceptibility to cervical cancer. This study evaluated the
      association between tumour necrosis factor-alpha (TNF-alpha)-308, transforming
      growth factor-beta 1 (TGF-beta1), interferon-gamma (IFN-gamma)+874 and
      interleukin-10 (IL-10)-1082 gene polymorphisms and cervical cancer risk. STUDY
      DESIGN: The study population included 186 histopathologically confirmed cases of
      cervical cancer and 200 healthy controls. TNF-alpha, TGF-beta, IL-10 and IFN
      gamma gene polymorphisms were genotyped by polymerase chain reaction with
      sequence-specific primers. RESULTS: The IFN-gamma+874A/A genotype was associated
      with high risk for the development of cervical cancer [odds ratio (OR) 2.22,
      p=0.012], and the A allele was associated with a 1.47-fold increased risk of
      cervical cancer (p=0.009). In contrast, no significant difference was found in
      the frequencies of TNF-alpha-308G/A, TGF-beta1 codons 10 and 25 C/C-G/G and IL-10
      1082G/A gene polymorphisms between patients with cervical cancer and healthy
      controls. CONCLUSIONS: Homozygous IFN-gamma+874A/T polymorphisms may be
      associated with increased risk for the development of cervical cancer.

PMID- 21719188
TI  - A provider-based water planning and management model--WaterSim 4.0--for the
      Phoenix Metropolitan Area.
AB  - Uncertainty in future water supplies for the Phoenix Metropolitan Area (Phoenix)
      are exacerbated by the near certainty of increased, future water demands; water
      demand may increase eightfold or more by 2030 for some communities. We developed
      a provider-based water management and planning model for Phoenix termed WaterSim
      4.0. The model combines a FORTRAN library with Microsoft C# to simulate the
      spatial and temporal dynamics of current and projected future water supply and
      demand as influenced by population demographics, climatic uncertainty, and
      groundwater availability. This paper describes model development and rationale.
      Water providers receive surface water, groundwater, or both depending on their
      portfolio. Runoff from two riverine systems supplies surface water to Phoenix
      while three alluvial layers that underlie the area provide groundwater. Water
      demand was estimated using two approaches. One approach used residential density,
      population projections, water duties, and acreage. A second approach used per
      capita water consumption and separate population growth estimates. Simulated
      estimates of initial groundwater for each provider were obtained as outputs from
      the Arizona Department of Water Resources (ADWR) Salt River Valley groundwater
      flow model (GFM). We compared simulated estimates of water storage with empirical
      estimates for modeled reservoirs as a test of model performance. In simulations
      we modified runoff by 80%-110% of the historical estimates, in 5% intervals, to
      examine provider-specific responses to altered surface water availability for 33
      large water providers over a 25-year period (2010-2035). Two metrics were used to
      differentiate their response: (1) we examined groundwater reliance (GWR; that
      proportion of a providers' portfolio dependent upon groundwater) from the runoff
      sensitivity analysis, and (2) we used 100% of the historical runoff simulations
      to examine the cumulative groundwater withdrawals for each provider. Four groups
      of water providers were identified, and discussed. Water portfolios most reliant
      on Colorado River water may be most sensitive to potential reductions in surface
      water supplies. Groundwater depletions were greatest for communities who were
      either 100% dependent upon groundwater (urban periphery), or nearly so, coupled
      with high water demand projections. On-going model development includes linking
      WaterSim 4.0 to the GFM in order to more precisely model provider-specific
      estimates of groundwater, and provider-based policy options that will enable
      "what-if" scenarios to examine policy trade-offs and long-term sustainability of
      water portfolios.

PMID- 21719189
TI  - Tasmanian landowner preferences for conservation incentive programs: a latent
      class approach.
AB  - An empirical model of landowners' conservation incentive program choice is
      developed in which information about landowners' socio-economic and property
      characteristics and their attitudes, is combined with incentive program
      attributes. In a Choice survey landowners were presented with the choice of two
      incentive programs modelled as 'bundles of attributes' mimicking a voluntary
      choice scenario. Landowner behaviour and decision and the type of conditions and
      regulations they preferred were analyzed. Based on choice survey data, landowner
      heterogeneity was accounted for using a latent class approach to estimate the
      preference parameters. Three latent classes of landowners with different
      attitudes to the role and outcome of establishing conservation reserves on
      private land were identified: multi-objective owners; environment owners; and
      production owners. Only a small proportion of landowners, mostly environment
      owners, would voluntarily join a program. Although compensation funding
      contributed to voluntary program choice for multi-objective owners and
      environment owners, welfare losses were around 4000 AUD per hectare, which is
      less than the average agricultural land value in Tasmania. Landowners for whom
      compensation funding contributed to voluntary program choice were also most
      likely to set aside land for conservation without payment. This raises the
      possibility that the government's compensation expenditure could potentially be
      either reduced or re-allocated to landowners who will not voluntarily take
      conservation action. Increasing participation in conservation incentive programs
      and minimizing the welfare losses associated with meeting conservation targets
      may be best achieved by offering programs that allow flexibility in terms of
      legal arrangements and other program attributes.

PMID- 21719191
TI  - Epigenetics in prostate cancer: biologic and clinical relevance.
AB  - CONTEXT: Prostate cancer (PCa) is one of the most common human malignancies and
      arises through genetic and epigenetic alterations. Epigenetic modifications
      include DNA methylation, histone modifications, and microRNAs (miRNA) and produce
      heritable changes in gene expression without altering the DNA coding sequence.
      OBJECTIVE: To review progress in the understanding of PCa epigenetics and to
      focus upon translational applications of this knowledge. EVIDENCE ACQUISITION:
      PubMed was searched for publications regarding PCa and DNA methylation, histone
      modifications, and miRNAs. Reports were selected based on the detail of analysis,
      mechanistic support of data, novelty, and potential clinical applications.
      EVIDENCE SYNTHESIS: Aberrant DNA methylation (hypo- and hypermethylation) is the
      best-characterized alteration in PCa and leads to genomic instability and
      inappropriate gene expression. Global and locus-specific changes in chromatin
      remodeling are implicated in PCa, with evidence suggesting a causative
      dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes
      to prostate carcinogenesis, including interference with androgen receptor
      signaling and apoptosis. There are important connections between common genetic
      alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape.
      Owing to the ubiquitous nature of epigenetic alterations, they provide potential
      biomarkers for PCa detection, diagnosis, assessment of prognosis, and post
      treatment surveillance. CONCLUSIONS: Altered epigenetic gene regulation is
      involved in the genesis and progression of PCa. Epigenetic alterations may
      provide valuable tools for the management of PCa patients and be targeted by
      pharmacologic compounds that reverse their nature. The potential for epigenetic
      changes in PCa requires further exploration and validation to enable translation
      to the clinic.

PMID- 21719190
TI  - Autoimmunity to uroplakin II causes cystitis in mice: a novel model of
      interstitial cystitis.
AB  - BACKGROUND: The pathophysiology of interstitial cystitis (IC) is unknown.
      Deficits in urothelial cell layers and autoimmune mechanisms may play a role.
      OBJECTIVE: To examine whether immunization of mice with recombinant mouse
      uroplakin II (rmUPK2), a bladder-specific protein, would provoke an autoimmune
      response sufficient to create an IC phenotype. DESIGN, SETTING, AND PARTICIPANTS:
      RmUPK2 complementary DNA was generated, transferred into a bacterial expression
      vector, and the generated protein was purified. Eight-week-old SWXJ female mice
      were immunized with rmUPK2 protein via subcutaneous injection of 200MUg of rmUPK2
      protein in 200MUl of an emulsion. MEASUREMENTS: Mice were euthanized 5 wk after
      immunization. Axillary and inguinal lymph node cells were tested for antigen
      specific responsiveness and cytokine production, serum isotype antibody titers
      against rmUPK2 were determined, and gene expression of inflammatory mediators was
      measured in the bladder and other organs. For functional analysis, mice were
      placed in urodynamic chambers for 24-h micturition frequency and total voided
      urine measurements. RESULTS AND LIMITATIONS: Immunization with rmUPK2 resulted in
      T-cell infiltration of the bladder urothelium and increased rmUPK2-specific serum
      antibody responses in the experimental autoimmune cystitis (EAC) mice models
      compared with controls. The ratio of bladder to body weight was increased in EAC
      mice. Quantitative reverse transcriptase polymerase chain reaction analysis
      showed elevated gene expression of tumor necrosis factor alpha, interferon gamma,
      interleukin (IL)-17A, and IL-1beta in bladder urothelium but not in other organs.
      Evaluation of 24-h micturition habits of EAC mice showed significantly increased
      urinary frequency (p<0.02) and significantly decreased urine output per void
      (p<0.021) when compared with control mice. CONCLUSIONS: Our study showed that a
      bladder-specific autoimmune response sufficient to induce inflammation and EAC
      occurs in mice following immunization with rmUPK2. EAC mice displayed significant
      evidence of urinary frequency and decreased urine output per void. Further
      phenotype characterization of EAC mice should include evidence for pain and/or
      afferent hypersensitivity, and evidence of urothelial cell layer damage.

PMID- 21719192
TI  - Sequential eluent injection technique as a new approach for the on-line
      enrichment and speciation of Cr(III) and Cr(VI) species on a single column with
      FAAS detection.
AB  - This paper introduces a sequential eluent injection (SEI) technique combined with
      an on-line preconcentration/separation system for a fast and sensitive FAAS
      determination of trace amounts of Cr(III) and Cr(VI) species. The method is based
      on the simultaneous retention of Cr(III) and Cr(VI) on a single mini-column
      packed with a chloromethylated polystyrene functionalized with N,N
      bis(naphthylideneimino)diethylenetriamine (PS-NAPdien) at pH 6.7. The retained
      chromium species was eluted by sequential injection of HCl for desorption of
      Cr(III), and NH(3) and NH(4)NO(3) buffer solutions for desorption of Cr(VI). All
      the chemical and flow injection variables were optimized for the quantitative
      preconcentration and speciation of Cr(III) and Cr(VI). Under the optimum
      conditions, the calibration graph obtained is linear over the concentration range
      of 2.0-60.0MUg L(-1) for Cr(III), and 8.0-180.0MUg L(-1) for Cr(VI). The
      preconcentration factors for Cr(III) and Cr(VI) were 70 and 30, respectively. The
      3sigma detection limits were 0.6MUg L(-1) and 2.5MUg L(-1) for Cr(III) and
      Cr(VI), respectively. The relative standard deviations were 2.55% and 0.8%,
      respectively, for 6 replicate determinations of Cr(III) and Cr(VI) at the 40.0MUg
      L(-1) level. The proposed method was applied for determination of Cr(III) and
      Cr(VI) in different water samples with satisfactory results.

PMID- 21719193
TI  - Influence of calcium hydroxide on the fate of perfluorooctanesulfonate under
      thermal conditions.
AB  - To explore the potential fate and transport of perfluorochemicals in the thermal
      treatment of sludge, perfluorooctanesulfonate (PFOS), a perfluorochemical species
      commonly dominant in wastewater sludge, was mixed with hydrated lime (Ca(OH)(2))
      to quantitatively observe their interaction under different temperatures. The
      phase compositions of the mixtures after the reactions were qualitatively
      identified and quantitatively determined using X-ray diffraction technique. The
      results of the thermogravimetry and differential scanning calorimetry analyses
      indicate that PFOS gasified directly during the thermal treatment process when
      the temperature was increased to around 425  degrees C. However, the formation of
      CaF(2) at 350  degrees C suggests that the presence of Ca(OH)(2) in the mixture
      can lead to the decomposition of PFOS at 350  degrees C, which is lower than the
      decomposition temperature of PFOS alone (425  degrees C). The increase of
      temperature promoted a solid state reaction between PFOS and Ca(OH)(2), and also
      enhanced the interaction between the gaseous products of PFOS and CaO (or
      Ca(OH)(2)). The preferred Ca/F molar ratio to achieve fluorine stabilization by
      Ca(OH)(2) was above 1:1 in the experiment involving 400  degrees C and 600 
      degrees C treatment. It also showed that equilibrium efficiency is achieved
      within 5 min at 400  degrees C and within 1 min above 600 degrees C.

PMID- 21719194
TI  - Novel hollow microspheres of hierarchical zinc-aluminum layered double hydroxides
      and their enhanced adsorption capacity for phosphate in water.
AB  - Hollow microspheres of hierarchical Zn-Al layered double hydroxides (LDHs) were
      synthesized by a simple hydrothermal method using urea as precipitating agent.
      The morphology and microstructure of the as-prepared samples were characterized
      by X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM),
      nitrogen adsorption-desorption isotherms and fourier transform infrared (FTIR)
      spectroscopy. It was found that the morphology of hierarchical Zn-Al LDHs can be
      tuned from irregular platelets to hollow microspheres by simply varying
      concentrations of urea. The effects of initial phosphate concentration and
      contact time on phosphate adsorption using various Zn-Al LDHs and their calcined
      products (LDOs) were investigated from batch tests. Our results indicate that the
      equilibrium adsorption data were best fitted by Langmuir isothermal model, with
      the maximum adsorption capacity of 54.1-232 mg/g; adsorption kinetics follows the
      pseudo-second-order kinetic equation and intra-particle diffusion model. In
      addition, Zn-Al LDOs are shown to be effective adsorbents for removing phosphate
      from aqueous solutions due to their hierarchical porous structures and high
      specific surface areas.

PMID- 21719195
TI  - A kinetic spectrophotometric method for simultaneous determination of phenol and
      its three derivatives with the aid of artificial neural network.
AB  - A novel kinetic spectrophotometric method was developed for determination of
      pyrocatechol, resorcin, hydroquinone and phenol based on their inhibitory effect
      on the oxidation of Rhodamine B (RhB) in acid medium at pH=3.0. A linear
      relationship was observed between the inhibitory effect and the concentrations of
      the compounds. The absorbance associated with the kinetic reactions was monitored
      at the maximum wavelength of 557nm. The effects of different parameters such as
      pH, concentration of RhB and KBrO(3), and temperature of the reaction were
      investigated and optimum conditions were established. The linear ranges were 0.22
      3.30, 0.108-0.828, 0.36-3.96 and 1.52-19.76MUg mL(-1) for pyrocatechol, resorcin,
      hydroquinone and phenol, respectively, and their corresponding detection limits
      were 0.15, 0.044, 0.16 and 0.60MUg mL(-1). The measured data were processed by
      several chemometrics methods, such as principal component regression (PCR),
      partial least squares (PLS) and artificial neural network (ANN), and a set of
      synthetic mixtures of these compounds was used to verify the established models.
      It was found that the prediction ability of PLS, PCR and RBF-ANN was similar,
      however, the RBF-ANN model did perform somewhat better than the other methods.
      The proposed method was also applied satisfactorily for the simultaneous
      determination of pyrocatechol, resorcin, hydroquinone and phenol in real water
      samples.

PMID- 21719197
TI  - Blocking the effects of NGF as a route to safe and effective pain relief--fact or
      fancy?

PMID- 21719198
TI  - Serological survey and risk factors for Toxoplasma gondii in domestic ducks and
      geese in Lower Saxony, Germany.
AB  - To obtain estimates for the prevalence of Toxoplasma gondii infection in ducks
      and geese in Germany, enzyme-linked immunosorbent assays (ELISA) were established
      based on affinity-purified T. gondii tachyzoite surface antigen 1 (TgSAG1) and
      used to examine duck and goose sera for T. gondii-specific antibodies. The
      results of 186 sera from 60 non-infected ducks (Anas platyrhynchos) and 101 sera
      from 36 non-infected geese (Anser anser) as well as 72 sera from 11 ducks and 89
      sera from 12 geese inoculated experimentally with T. gondii tachyzoites
      (intravenously) or oocysts (orally) and positive in a T. gondii immunofluorescent
      antibody test (IFAT) were used to select a cut-off value for the TgSAG1-ELISA.
      Sera obtained by serial bleeding of experimentally inoculated ducks and geese
      were tested to analyze the time course of anti-TgSAG1 antibodies after
      inoculation and to assess the sensitivity of the assays in comparison with IFAT.
      In ducks, IFAT titres and ELISA indices peaked 2 and 5 weeks p.i with
      tachyzoites, respectively. Only three of six geese inoculated with tachyzoites at
      the same time as the ducks elicited a low and non-permanent antibody response as
      detected by the IFAT. In the TgSAG1-ELISA, only a slight increase of the ELISA
      indices was observed in four of six tachyzoite-inoculated geese. By contrast,
      inoculation of ducks and geese with oocysts led to an increase in anti-TgSAG1
      antibodies within 1 or 2 weeks, which were still detectable at the end of the
      observation period, i.e. 11 weeks p.i. Inoculation of three ducks and three geese
      with oocysts of Hammondia hammondi, a protozoon closely related to T. gondii,
      resulted in a transient seroconversion in ducks and geese as measured by IFAT or
      TgSAG1-ELISA. Using the newly established TgSAG1-ELISA, sera from naturally
      exposed ducks and geese sampled in the course of a monitoring program for avian
      influenza were examined for antibodies to T. gondii; 145/2534 (5.7%) of the ducks
      and 94/373 (25.2%) of the geese had antibodies against TgSAG1. Seropositive
      animals were detected on 20 of 61 duck and in 11 of 13 goose farms; the
      seroprevalences within positive submissions of single farms ranged from 2.2% to
      78.6%. Farms keeping ducks or geese exclusively indoors had a significantly lower
      risk (odds ratio 0.05, 95% confidence interval 0.01-0.3) of harboring
      serologically positive animals as compared with farms where the animals had
      access to an enclosure outside the barn.

PMID- 21719199
TI  - Cryptosporidium and Giardia associated with reduced lamb carcase productivity.
AB  - On two extensive sheep farms in southern Western Australia, 111 (Farm A) and 124
      (Farm B) female crossbred lambs (2-6 weeks old) were randomly selected and
      individually identified using ear tags (a numbered tag and radio-frequency tag)
      at marking. On five separate occasions, faecal samples were collected and live
      weight, body condition score (BCS), faecal consistency score (FCS), breech fleece
      faecal soiling score and faecal dry matter percentage (DM%) were recorded. Lamb
      hot carcase weight (HCW) and dressing percentage were measured at slaughter.
      Faecal samples were screened by PCR for Cryptosporidium (18S rRNA, actin and 60
      kDa glycoprotein [gp60] loci), Giardia duodenalis (glutamate dehydrogenase [gdh]
      and triosephosphate isomerise [tpi]) and Campylobacter jejuni (16S rRNA).
      Observation of Eimeria oocysts and faecal worm egg counts (WECs) were performed
      using a modified McMaster technique. The WECs were adjusted for FCS for analyses.
      Faecal samples were screened for patent strongylid infections using PCR
      (specifically ITS-2 nuclear ribosomal DNA for Teladorsagia circumcincta,
      Trichostrongylus spp. and Haemonchus contortus). Lambs positive for
      Cryptosporidium at least once had lighter HCWs by 1.25 kg (6.6%) (P=0.029) and
      1.46 kg (9.7%) (P<0.001) compared to lambs never positive for Cryptosporidium for
      Farms A and B respectively. Similarly, dressing percentages were 1.7% (P=0.022)
      and 1.9% (P<0.001) lower in Cryptosporidium-positive lambs on Farms A and B
      respectively. Lambs positive for Giardia at least once had 0.69 kg (P<0.001)
      lighter HCWs and 1.7% (P<0.001) lower dressing percentages compared to lambs
      never positive for Giardia on Farm B only. Cryptosporidium-positive lambs at the
      second sampling were 4.72 (P=0.010) and 3.84 (P=0.002) times more likely to have
      non-pelleted faeces compared to Cryptosporidium-negative lambs for Farms A and B
      respectively. Breech fleece faecal soiling scores of Cryptosporidium-positive
      lambs were 3.36 (P=0.026) and 2.96 (P=0.047) times more likely to be moderate to
      severe (scores 3-5), compared to negative lambs at the second sampling for Farms
      A and B respectively. Live weight, growth rate and BCS were inconsistently
      associated with protozoa detection across different samplings and farms. Adjusted
      WEC was correlated positively with FCS and negatively with faecal DM%, differing
      between sampling occasions and farms. Campylobacter jejuni prevalence was very
      low (<1%). Adjusted WEC were not correlated with carcase attributes, growth rates
      or live weights. This study is the first to quantify productivity consequences of
      naturally acquired protozoa infections in lambs managed under extensive farming
      conditions.

PMID- 21719200
TI  - Comments on "Electricity and fishing--a dangerous mix".

PMID- 21719201
TI  - Diurnal cortisol rhythms in Tsimane' Amazonian foragers: new insights into
      ecological HPA axis research.
AB  - Although a growing body of research has documented important pathways by which
      the HPA axis mediates the interface between the psychosocial world and individual
      health, there is a paucity of data from nonwestern populations, particularly from
      those populations with distinct nutritional and infectious disease ecologies. The
      specific objectives of this study are: (1) to document variation in diurnal
      cortisol rhythms among the Tsimane', a remote population in the Bolivian Amazon,
      (2) to explore this variation by age and by gender, and (3) to compare diurnal
      rhythms from this study to other population based studies of cortisol conducted
      in industrialized nations. Salivary cortisol samples were collected twice daily,
      immediately upon waking and before bed, for three consecutive days from 303
      participants (age 1.6-82 years, 1564 samples) in conjunction with the Tsimane'
      Amazonian Panel Study (TAPS). Cortisol rhythms showed strong age effects across
      the developmental span, with basal levels and slopes increasing into adulthood,
      although individuals older than 60 years demonstrated a precipitous flattening of
      the diurnal slope. Cortisol profiles were elevated in adult females compared to
      their age-matched male counterparts, and diurnal slopes, as well as mean cortisol
      concentrations among the Tsimane' were the lowest reported in any population
      based study of HPA axis function. Although the within-population variation in
      cortisol profiles was consistent with the established correlates of time of day,
      age, and sex, the between-population comparisons revealed dramatically lower
      levels of HPA activity among the Tsimane'. This study provides a benchmark
      against which to reference cortisol levels from industrialized populations, and
      expands the range of documented variation in HPA axis function in a nonwestern
      context.

PMID- 21719202
TI  - Coping motives as a mediator of the relationship between sexual coercion and
      problem drinking in college students.
AB  - Sexually coercive experiences, heavy alcohol use, and alcohol-related problems
      occur at relatively high base rates in college populations. As suggested by the
      self-medication hypothesis, alcohol consumption may be a means by which one can
      reduce negative affect or stress related to experiences of sexual coercion.
      However, few studies have directly tested the hypothesis that coping motives for
      drinking mediate the relation between sexual assault and problem drinking
      behaviors, and no published studies have tested this in men. The current study
      tested this hypothesis using structural equation modeling in a sample of 780 male
      and female undergraduates. Results revealed that coping motives partially
      mediated the relation between sexual coercion and drinking and alcohol-related
      negative consequences. In addition, direct and indirect paths between sexual
      coercion and drinking were found for men whereas only indirect paths were found
      for women. Results provide support for self-medication models of drinking and
      suggest the importance of exploring gender differences in mechanisms for
      drinking.

PMID- 21719203
TI  - Use and correlates of protective drinking behaviors during the transition to
      college: analysis of a national sample.
AB  - OBJECTIVE: This study examined patterns and correlates of protective drinking
      behaviors among incoming first-year college students. METHOD: Incoming first-year
      students (n=76,882) from 258 colleges across the U.S. provided baseline data on
      demographics, drinking practices, and protective behaviors as part of a web-based
      alcohol education program. Across the several colleges, responses to protective
      behavior questions were collected from seven weeks before the start of the school
      year to five weeks after. RESULTS: Factor analysis identified three protective
      behavior sub-factors: Limit Drinking, Avoid Drinking and Driving, and Intent to
      Get Drunk. Both Limit Drinking and Avoid Drinking and Driving generally declined
      over the course of the data collection period while Intent to Get Drunk and peak
      blood alcohol concentration increased immediately after the start of school. In
      multiple regression analyses, the number of heavy drinking episodes in the past
      two weeks had a strong negative association with a Total Protective Behavior
      Score and the Limit Drinking Score, and a positive association with the Intent to
      Get Drunk Score. With the exception of the Intent to Get Drunk Score, women were
      more likely to use protective behaviors than men. Underage drinkers used
      protective behaviors less often than their of-age peers, though the effect was
      small. Race/ethnicity, time to matriculation, and intent to join/membership in a
      fraternity/sorority had negligible effects on protective behavior scores.
      CONCLUSIONS: College students increase risky drinking after the start of school
      while progressively using fewer behaviors that might mitigate the consequences of
      drinking.

PMID- 21719205
TI  - Does the association with diabetes say more about schizophrenia and its
      treatment?--the GLUT hypothesis.
AB  - All effective anti psychotic drugs block glucose transporter proteins (GLUTs),
      peripherally and in the brain. These drugs are implicated in hyperglycaemia as
      demonstrated in mouse and human studies. Clozapine is the strongest blocker, with
      Haloperidol the weakest. The GLUT hypothesis suggests that schizophrenia is
      partly due to poor functioning of brain glucose transporters (GLUT 1 and 3).
      Neuronal glucose malnutrition could result in excessive neuronal pruning (so
      called Crow's Type 2 with a predominance of negative symptoms) or result in
      recurrent/ineffective pruning (Type 1 with positive symptoms). GLUT blockade by
      anti psychotic agents could assist Type 1 patients to complete the pruning
      process by deactivating already damaged neurones and circuits, but will make Type
      2 patients more cognitively impaired. Future treatment options are discussed in
      line with the above formulation.

PMID- 21719204
TI  - A prospective examination of the relationships between PTSD, exposure to
      assaultive violence, and cigarette smoking among a national sample of
      adolescents.
AB  - Research demonstrates robust associations among posttraumatic stress disorder
      (PTSD), exposure to assaultive violence (i.e., sexual assault, physical assault,
      and witnessed violence), and cigarette smoking among adults and adolescents.
      Whether exposure to assaultive violence confers risk for cigarette smoking over
      and above the effects of PTSD and non-assaultive traumatic events (e.g., motor
      vehicle accidents) is unclear. The current study prospectively measured PTSD,
      assaultive violence exposure, non-assaultive traumatic event exposure, and
      cigarette smoking three times over approximately three years among a nationally
      representative sample of adolescents (N=3614, age range 12-17 at Wave 1). Results
      revealed that multiple exposure to assaultive violence at Wave 1 was a consistent
      and robust prospective predictor of cigarette smoking at Waves 2 and 3. By
      contrast, PTSD diagnoses and non-assaultive traumatic event exposures at Wave 1
      only predicted cigarette smoking at Wave 2, but not at Wave 3. Theoretical and
      clinical implications are discussed.

PMID- 21719206
TI  - Does CYP2C19 inhibition lead to clopidogrel thrombogenicity?
AB  - There exits an ongoing debate regarding potential hazards associated with
      concomitant use of clopidogrel and proton-pump inhibitors. In this manuscript, a
      meta-analysis of mortality data demonstrates that the mortality prevented by
      clopidogrel is significantly lower than the mortality caused by clopidogrel and
      proton-pump inhibitor combination. Given the hazards associated with the
      combination, abating the positive effect of clopidogrel is not a satisfactory
      explanation. Thus a hypothesis is proposed, that the combination of proton-pump
      inhibitors and clopidogrel increases mortality as results of thrombogenic
      metabolites of clopidogrel, due to inhibition of CYP2C19 by proton-pump
      inhibitors.

PMID- 21719207
TI  - Heat-induced gelation of myosin in a low ionic strength solution containing L
      histidine.
AB  - Binding properties are important for meat products and are substantially derived
      from the heat-induced gelation of myosin. We have shown that myosin is
      solubilized in a low ionic strength solution containing L-histidine. To clarify
      its processing characteristics, we investigated properties and structures of heat
      induced gels of myosin solubilized in a low ionic strength solution containing L
      histidine. Myosin in a low ionic strength solution formed transparent gels at 40
      50 degrees C, while myosin in a high ionic strength solution formed opaque gels
      at 60-70 degrees C. The gel of myosin in a low ionic strength solution with L
      histidine showed a fine network consisting of thin strands and its viscosity was
      lower than that of myosin in a high ionic strength solution at 40-50 degrees C.
      The rheological properties of heat-induced gels of myosin at low ionic strength
      are different from those at high ionic strength. This difference might be caused
      by structural changes in the rod region of myosin in a low ionic strength
      solution containing L-histidine.

PMID- 21719208
TI  - Overexpression of EZH2 and loss of expression of PTEN is associated with
      invasion, metastasis, and poor progression of gallbladder adenocarcinoma.
AB  - Overexpression of EZH2 and inactivation or loss of PTEN expression was observed
      in invasive and metastatic tumors. However, their expressions and clinical
      significances in gallbladder cancer (GBC) have rarely been reported. In this
      study, we investigated EZH2 and PTEN expression in an extensive collection of
      human gallbladder cancer samples and benign lesions of gallbladder using
      immunohistochemistry. Overexpression of EZH2 was detected in 53.7% of gallbladder
      adenocarcinomas associated with poor differentiation, lymph node metastasis, and
      invasion, while loss of PTEN expression was identified in 51.8% of
      adenocarcinomas with high grade, metastatic, and invasive tumors. Univariate
      Kaplan-Meier analysis showed that overexpression of EZH2 (p=0.013) and loss of
      PTEN expression (p=0.008) were significantly associated with decreased overall
      survival. Multivariate Cox regression analysis revealed that overexpression of
      EZH2 (p=0.011) or loss of PTEN expression (p=0.009) is a predictor of poor
      prognosis in gallbladder adenocarcinoma. Our study suggests that overexpression
      of EZH2 and loss of PTEN expression might be closely related to the
      carcinogenesis, progression, clinical biological behavior, and prognosis of
      gallbladder adenocarcinoma.

PMID- 21719209
TI  - Validation of imaging with pathology in laryngeal cancer: accuracy of the
      registration methodology.
AB  - PURPOSE: To investigate the feasibility and accuracy of an automated method to
      validate gross tumor volume (GTV) delineations with pathology in laryngeal and
      hypopharyngeal cancer. METHODS AND MATERIALS: High-resolution computed tomography
      (CT(HR)), magnetic resonance imaging (MRI), and positron emission tomography
      (PET) scans were obtained from 10 patients before total laryngectomy. The GTV was
      delineated separately in each imaging modality. The laryngectomy specimen was
      sliced transversely in 3-mm-thick slices, and whole-mount hematoxylin-eosin
      stained (H&E) sections were obtained. A pathologist delineated tumor tissue in
      the H&E sections (GTV(PATH)). An automatic three-dimensional (3D) reconstruction
      of the specimen was performed, and the CT(HR), MRI, and PET were
      semiautomatically and rigidly registered to the 3D specimen. The accuracy of the
      pathology-imaging registration and the specimen deformation and shrinkage were
      assessed. The tumor delineation inaccuracies were compared with the registration
      errors. RESULTS: Good agreement was observed between anatomical landmarks in the
      3D specimen and in the in vivo images. Limited deformations and shrinkage (3% +/-
      1%) were found inside the cartilage skeleton. The root mean squared error of the
      registration between the 3D specimen and the CT, MRI, and PET was on average 1.5,
      3.0, and 3.3 mm, respectively, in the cartilage skeleton. The GTV(PATH) volume
      was 7.2 mL, on average. The GTVs based on CT, MRI, and PET generated a mean
      volume of 14.9, 18.3, and 9.8 mL and covered the GTV(PATH) by 85%, 88%, and 77%,
      respectively. The tumor delineation inaccuracies exceeded the registration error
      in all the imaging modalities. CONCLUSIONS: Validation of GTV delineations with
      pathology is feasible with an average overall accuracy below 3.5 mm inside the
      laryngeal skeleton. The tumor delineation inaccuracies were larger than the
      registration error. Therefore, an accurate histological validation of anatomical
      and functional imaging techniques for GTV delineation is possible in laryngeal
      cancer patients.

PMID- 21719210
TI  - Preliminary results of fractionated stereotactic radiotherapy after cyst drainage
      for craniopharyngioma in adults.
AB  - PURPOSE: To retrospectively evaluate the effectiveness of fractionated
      stereotactic radiotherapy (FSRT) for craniopharyngioma. METHODS AND MATERIALS:
      Between 1999 and 2005, 16 patients with craniopharyngioma were referred to Tokyo
      Medical University Hospital. They received FSRT alone after histologic
      confirmation by needle biopsy and underwent cyst drainage via endoscopy. The
      median prescription dose fraction was 30 Gy in six fractions. All patients except
      1 were followed up until December 2009 or death. RESULTS: The median follow-up
      period was 52 months (range, 4-117 months). Of the 17 patients, 3 experienced
      recurrence 4 to 71 months after FSRT. The 3-year local control rate was 82.4%.
      One patient died of thyroid cancer, and the 3-year survival rate was 94.1%. Eight
      patients had improved visual fields at a median of 2.5 months after FSRT, but
      hormonal functions did not improve in any patient. CONCLUSIONS: FSRT after cyst
      drainage seems to be safe and effective for patients with craniopharyngiomas, and
      it may be a safe alternative to surgery.

PMID- 21719211
TI  - The effect of distal radius locking plates on articular contact pressures.
AB  - PURPOSE: Fractures of the distal radius are among the most common injuries
      treated in hand surgery practice, and distal radius locking plates have become an
      increasingly popular method of fixation. Despite widespread use of this
      technology, it is unknown whether the subchondral placement of locking screws
      affects the loading profile of the distal radius. Our study was designed to
      determine whether subchondral locking screws change the articular contact
      pressures in the distal radius. METHODS: Twelve cadaveric forearms underwent a
      previously described axial loading protocol in a materials testing machine. We
      used an intra-articular, real-time computerized force sensor to measure peak
      contact pressure, total pressure, and contact area in the distal radius. Internal
      validation of sensor placement and reproducibility was conducted. Each specimen
      was tested before fixation (control), after application of a palmar distal radius
      locking plate, and after simulation of a metaphyseal fracture. RESULTS: We
      identified no statistically significant differences in maximum pressure, total
      pressure, and contact area among control, plated, and plated and fractured
      specimens. However, the contact footprint-represented by squared differences in
      force across the sensor-were significantly different between the control group
      and both plated groups. CONCLUSIONS: The technique for measuring contact
      pressures produces highly repeatable values. Distal radius locking plates with
      subchondral hardware placement do not seem to significantly change articular
      contact pressures.

PMID- 21719212
TI  - [Evolution of susceptibility to antibiotics of Escherichia coli, Klebsiella
      pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumanii, in a University
      Hospital Center of Beirut between 2005 and 2009].
AB  - INTRODUCTION: Until recently, multiresistant bacteria were only limited to
      hospitals. However, they are now responsible for community acquired infections,
      affecting people who have had no contact with the hospital environment. Several
      mechanisms are associated with these resistances. The production of
      betalactamases is however the predominant mechanism and especially the production
      of extended spectrum beta-lactamases or ESBL by strains of Escherichia coli and
      Klebsiella pneumoniae, which mediate resistance to third generation
      cephalosporins and aztreonam (AZT). The association of multiple mechanisms of
      resistance (efflux pumps, impermeability and enzymatic inactivation) generates
      multi resistant bacteria such as Pseudomonas aeruginosa MDR and Klebsiella
      pneumoniae MDR. AIM OF THE STUDY: The aim of the study was to analyze
      retrospectively the susceptibility to antibiotics of strains of E. coli, K.
      pneumoniae, P. aeruginosa and A. baumanii isolated from hospitalized and
      outpatients in a university hospital center of Beirut over a period of five years
      from 2005 to 2009. MATERIALS AND METHODS: Bacterial strains were classified
      according to their origin (inpatients versus outpatients), their ability to
      produce or not ESBLs for E. coli and K. pneumonia and if they were MDR for P.
      aeruginosa and A. baumanii. Antibiotics susceptibilities were retrieved from the
      informatics database of the hospital. Comparison of susceptibility percentages
      was done using a unilateral z-test on a computer program. RESULTS: In 2009, 2541
      strains of E. coli were isolated, 773 of which or 30.4 % were ESBL producers
      while 2031 strains were isolated in 2005, of which 361 or 17.8 % were ESBL
      producers (p<0.001). We noticed a decrease in hospital strains susceptibility to
      ceftazidime (CAZ) and AZT, between 2005 and 2009 (p<0.001), and a decrease in
      community strains susceptibility to trimethoprime/sulfamethoxazole (SXT) between
      2005 and 2009 (p=0.03). We noted however a significant decrease of ESBL producing
      strains between 2007 and 2009: 33.4 % versus 30.4 % (p=0.03). Among 560 strains
      of K. pneumoniae isolated in 2009, 178 strains or 31.8 % were ESBL producers in
      comparison to 23.7 % of the strains isolated in 2005 (p=0.03). We also noticed a
      decrease in hospital strains susceptibility to piperacilline-tazobactam (TZP),
      cefotaxime (CTX) and AZT (p<0.001 p=0.03 and p=0.03 respectively) between 2006
      and 2009, and a significant increase in ESBL producing strains between 2008 et
      2009 (p=0.0001). 26.5 % of P. aeruginosa strains isolated in 2009 were MDR
      bacteria with no significant change as compared to 26.6 % in 2005 (p=0.5).
      However, the percentage of MDR strains slightly decreased between 2008 and 2009
      (p=0.047). The susceptibility of MDR strains to CAZ and imipenem (IMP) decreased
      between 2005 and 2009 (p<0.001 and P=0.003 respectively). As for A. baumanii,
      77.7 % of strains were MDR in 2009 in comparison to 73.4 % in 2005 (p=0.24) with
      a dramatic decrease of MDR strains susceptibility to IMP from 92.3 % in 2006 to
      30 % in 2009 (p<0.001). CONCLUSION: Despite restrictions on antibiotics
      prescriptions and isolation of patients harboring MDR bacteria or bacteria
      producing ESBL, there has not been satisfactory reduction of multi resistant
      bacteria and efforts should be made to reduce these bugs from the hospital flora.

PMID- 21719213
TI  - Endothelial dysfunction during acute alcohol withdrawal syndrome.
AB  - BACKGROUND: Endothelial dysfunction (EF) is a central phenomenon in a variety of
      conditions associated with increased cardiovascular morbidity. Here, we
      investigated EF during acute alcohol withdrawal syndrome before and 24h after
      medication. We aimed to analyze microcirculation, applying the post-occlusive
      reactive hyperemia (PORH) test and spectral analysis of skin vasomotion as
      markers of EF. Additionally, we explored whether segmentation of spectral
      analysis data may disclose more detailed information on dynamic blood flow
      behavior. METHODS: We investigated 30 unmedicated patients during acute alcohol
      withdrawal syndrome and matched controls. Patients were reinvestigated after 24h
      when half of them had been treated with clomethiazole. Capillary blood flow was
      assessed on the right forearm after compression of the brachial artery.
      Parameters of PORH such as time to peak (TP), slope and PORH indices were
      calculated. Spectral analysis was performed in order to study five different
      frequency bands. Withdrawal symptoms were quantified by means of the alcohol
      withdrawal scale (AW scale). RESULTS: We observed a blunted hyperemic response in
      patients after occlusion of the brachial artery indicated by significantly
      increased TP and decreased PORH indices. In contrast, vasomotion as investigated
      by spectral analysis was not altered. Segmentation analysis revealed some
      alterations in the cardiac band at rest, and indicated differences between
      treated and untreated patients after 24h. CONCLUSION: Our results suggest
      peripheral endothelial dysfunction in patients during acute alcohol withdrawal.
      No major influence of treatment was observed. Future studies need to address the
      relation of EF to cardiac morbidity during alcohol withdrawal.

PMID- 21719214
TI  - The needle and the damage done: clinical and behavioural markers of severe
      femoral vein damage among groin injectors.
AB  - AIM: To identify factors associated with severe femoral vein (FV) damage among
      groin injectors (GIs) on oral opioid substitution treatment. DESIGN: A cohort
      study. SETTING: Drug treatment centres in South East England. PARTICIPANTS: GIs
      attending an ultrasound 'health-check' clinic. MEASURES: Femoral ultrasonography
      and clinical grading of venous disease in each leg. METHOD: Comparison of 67 GIs
      with severely damaged FV and 86 GIs with minimal/moderate damage. FINDINGS: The
      majority were men (69.3%) and the mean age was 36.2 years with mean duration of
      injecting drug use (IDU) of 13.3 years. There were no significant between-group
      differences in age, gender or duration of IDU. Severe FV damage was associated
      with longer duration of groin injecting (GI; P<0.005), use of thick needles (blue
      hub, 23G; or green-hub, 21G; P<0.001), benzodiazepine injection (P<0.005),
      history of deep vein thrombosis (DVT, P<0.001) and recurrent DVT (P<0.001),
      presence of depressed groin scar (P<0.001) and chronic venous disease (CVD,
      P<0.001). Logistic regression analysis revealed needle size (beta 1.2, Wald 4.9,
      P<0.05) and DVT (beta 3.3, Wald 38.5, P<0.001) as the main predictors of severe
      FV damage. CONCLUSION: Needle and syringe exchange services should consider only
      supplying appropriate lengths of orange-hub needle (25G) on request from GIs.
      Early cessation of GI, avoidance of benzodiazepine injection and prompt diagnosis
      and treatment of DVT might also reduce the prevalence of severe FV damage among
      GIs and the associated healthcare burden. Routine examination of injecting sites
      among these patients should include an assessment of severity of venous disease
      in each leg.

PMID- 21719215
TI  - Torque teno sus virus 1 and 2 viral loads in postweaning multisystemic wasting
      syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS) affected
      pigs.
AB  - Torque teno viruses (TTV) are small, non-enveloped viruses with a circular single
      stranded DNA genome, which are considered non-pathogenic. However, TTVs have been
      eventually linked to human diseases. TTVs infecting pigs, Torque teno sus virus 1
      (TTSuV1) and 2 (TTSuV2), have been recently associated to porcine circovirus
      diseases (PCVD). To get more insights into such potential disease association,
      the aim of this study was to quantify TTSuV1 and TTSuV2 viral loads in serum of
      pigs affected by two PCVDs, postweaning multisystemic wasting syndrome (PMWS) and
      porcine dermatitis and nephropathy syndrome (PDNS). Such study was carried out by
      means of a newly developed real-time quantitative PCR (qPCR) method. Both TTSuVs
      were highly prevalent among studied pigs. TTSuV2 viral loads were significantly
      higher in PMWS affected animals, further supporting the previously suggested
      association between TTSuV2 and PMWS. On the contrary, TTSuV1 prevalence and loads
      were not related with the studied PCVDs.

PMID- 21719216
TI  - Rabbit haemorrhagic disease: advantages of cELISA in assessing immunity in wild
      rabbits (Oryctolagus cuniculus).
AB  - Rabbit haemorrhagic disease (RHD) is an acute fatal disease of domestic and wild
      European rabbits (Oryctolagus cuniculus) caused by RHD virus (RHDV). Accurate
      assessment of immunity is of great importance for the conservation and control of
      wild rabbits. We evaluated a competitive ELISA (cELISA) against isotype ELISAs
      for assessing the protective immunity against the disease by challenging 50 wild
      caught rabbits with a lethal dose of RHDV. Death or survival to the challenge was
      used as a criterion to determine the performance characteristics of the assay for
      the assessment of immunity in rabbits. At 1:10 dilution, a serum exhibiting >=
      25% inhibition (1:10(25)) was regarded as the presence of RHDV-specific
      antibodies. Eleven of 16 (68.8%) rabbits with antibodies at 1:10(25) (<1:40) died
      of RHD. When the cut-off was moved from 25% to 50% inhibition (1:10(50)) at 1:10
      serum dilution, the assay sensitivity, specificity and accuracy for the
      protective immunity were improved from 84%, 54.2% and 69.4% to 84%, 100% and
      91.8%, respectively. We also demonstrated at the epitope amino acid sequence
      level why the presence of the RHDV-cross reactive benign rabbit calicivirus,
      which interfered with isotype ELISAs, had little impact on the specificity of the
      cELISA for the diagnosis of RHDV infection. The presence of RHDV-specific
      antibody at 1:10(50) by the cELISA is a reliable indicator for the protective
      immunity. In contrast to isotype ELISAs, the cELISA is a valuable specific tool
      for monitoring the herd immunity to RHD for the conservation and management of
      wild rabbits in the field.

PMID- 21719217
TI  - Functional and molecular characterization of maxi K+ -channels (BK(Ca)) in
      buffalo myometrium.
AB  - Large conductance potassium channels (BK(Ca) channels) play a central role in
      maintaining myometrial tone, thus activation of these channels proved to have
      therapeutic potential in preterm labor. Present study aims to unravel the
      presence of BK(Ca) (maxi-K) channels in buffalo myometrium. Tension experiments,
      mRNA and protein expression studies were done to characterize BK(Ca) channels in
      buffalo myometrium. Isolated myometrial preparations exhibited rhythmic
      spontaneity with regular pattern of amplitude and frequency. Selective blockers
      of BK(Ca) channels iberiotoxin (IbTx; 100nM) and tetraethylammonium (TEA; 1mM)
      produced excitatory effects as evidenced by increase in amplitude and frequency
      of myogenic activity. 1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5
      (trifluoromethyl)-2H-benzimi-dazol-2-one (NS-1619; 10(-7)-10(-4)M), a BK(Ca)
      channel opener, produced concentration-dependent relaxation of myometrium with
      pD(2) of 5.02+/-0.19 and R(max) of 31.35+/-3.5% (n=5). TEA significantly
      antagonized NS-1619-induced relaxation (pD(2) of 4.72+/-0.12 and R(max) of
      22.72+/-1.78%; n=5). IbTx also significantly shifted the dose response curve of
      NS-1619 towards right (pD(2) of 3.98+/-0.16; n=4) without significant change in
      the per cent maximal response. Further, RT-PCR study detected mRNA encoding
      BK(Ca) alpha-subunit and Western blot analysis detected its protein expression in
      myometrium. Based on the results of the present investigation, it is suggested
      that BK(Ca) channels are present in the buffalo myometrium and are open in the
      resting state. Thus, their activation by potassium channel opener/beta(2)
      adrenoceptor agonist (tocolytic drug) may lead to uterine relaxation in preterm
      labor.

PMID- 21719218
TI  - Spermatogonial stem cells in the testis of an endangered bovid: Indian black buck
      (Antilope cervicapra L.).
AB  - Numerous wild bovids are facing threat of extinction owing to the loss of habitat
      and various other reasons. Spermatogonial stem cells (SSCs) represent the only
      germline stem cells in adult body that are capable of self-renewal and that can
      undergo differentiation to produce haploid germ cells. SSCs can, therefore, serve
      as a useful resource for preservation of germplasm of threatened and endangered
      mammals. The Indian black buck (Antilope cervicapra L.) is a small Indian
      antelope that is listed as endangered by the Indian Wildlife Protection Act,
      1972. Immunohistochemical analysis of testes tissues of black buck revealed the
      presence of spermatogonia that were specifically stained by lectin-Dolichos
      biflorus agglutinin (DBA). The expression of pluripotent cell-specific markers,
      NANOG and stage-specific embryonic antigen-1 (SSEA-1), was detected in
      spermatogonia. Interestingly, the expression of POU5F1 (OCT3/4) was absent from
      spermatogonia, however, it was detected in differentiating cells such as
      spermatocytes and round spermatids but not in elongated spermatids. The
      expression of NANOG protein was also present in spermatocytes but absent in round
      and elongated spermatids. Using the testis transplantation assay, stem cell
      potential of black buck spermatogonia was confirmed as indicated by the presence
      of colonized DBA-stained cells in the basal membrane of seminiferous tubules of
      xenotransplanted mice testis. The findings from this study suggest the presence
      of SSCs in the testis of an endangered bovid for the first time and open new
      possibility to explore the use of SSCs in conservation.

PMID- 21719219
TI  - Thyroid disease in older people.
AB  - Several changes in thyroid hormone secretion, metabolism, and action occur with
      the increase in age. Aging is often associated with a decrease in serum thyroid
      stimulating hormone and T3 levels, whereas serum free T4 levels usually remain
      unchanged. The prevalence of thyroid dysfunction is higher in the elderly as
      compared to the younger population. In elderly individuals the non-specific
      clinical manifestations of thyroid hormone excess or deprivation can cause
      confusion in the clinical setup; while some of the symptoms of thyroid disease
      are similar to those in younger patients, it is not uncommon for both
      hyperthyroidism and hypothyroidism to be manifested in subtle ways in older
      patients, often mimicking symptoms of aging or masquerading as diseases of the
      cardiovascular, gastrointestinal, or nervous system. In addition, diagnosis of
      thyroid disorders is commonly complicated, due to chronic, non-thyroidal illness
      or medication therapy. Early diagnosis and treatment of overt thyroid disorders
      is crucial, since these disorders are associated with increased morbidity and
      mortality in the elderly, usually due to common coexistent diseases such as
      diminished cardiovascular reserve. Treatment of subclinical thyroid disease
      should also be considered, based on a combination of age, symptoms and risk
      factors in the individual patients. In addition, both prevalence and
      aggressiveness of thyroid cancer increase with age. This review summarizes the
      changes of thyroid function, as well as the clinical manifestations and treatment
      of thyroid disorders with advancing age.

PMID- 21719220
TI  - The effect of relative humidity on the effectiveness of the cyanoacrylate fuming
      process for fingermark development and on the microstructure of the developed
      marks.
AB  - Research has been conducted to establish the effect that changes in relative
      humidity have on both the effectiveness of the cyanoacrylate fuming technique and
      the microstructures formed by the polymerisation reaction during the development
      of the marks. The study investigated 'natural' fingermarks and deliberately
      groomed eccrine and sebaceous marks, all exposed to relative humidity levels in
      the range 60-100%. It was found that the optimum level of relative humidity for
      the development of the most high quality marks is approximately 80%, in accord
      with current recommendations for operational implementation which are based on
      previous unpublished work. The eccrine constituents of the fingerprints are most
      influenced by humidity changes. Three humidity regimes were identified, each
      giving different polycyanoacrylate microstructures. Humidity levels of 60% give
      flat, film-like structures whereas in the range 70-90% the characteristic noodle
      like structure is formed. At higher humidities, thin, flat thread-like growth is
      observed with some 'collapsed sphere' structures observed close to pores and
      significant background development. The noodle-like structures are thought to
      scatter more light and retain fluorescent dye better than the structures formed
      at other humidity levels. Sebaceous marks produce a very different polymer
      microstructure, resembling a flat film with some fine nodular structures.

PMID- 21719221
TI  - A one-year monitoring of nicotine use in sport: frontier between potential
      performance enhancement and addiction issues.
AB  - Tobacco consumption is a global epidemic responsible for a vast burden of
      disease. With pharmacological properties sought-after by consumers and
      responsible for addiction issues, nicotine is the main reason of this phenomenon.
      Accordingly, smokeless tobacco products are of growing popularity in sport owing
      to potential performance enhancing properties and absence of adverse effects on
      the respiratory system. Nevertheless, nicotine does not appear on the 2011 World
      Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a
      comprehensive large-scale prevalence survey. Thus, this work describes a one-year
      monitoring study on urine specimens from professional athletes of different
      disciplines covering 2010 and 2011. A method for the detection and quantification
      of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine
      N'-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine
      and nornicotine) was developed, relying on ultra-high pressure liquid
      chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A
      simple and fast dilute-and-shoot sample treatment was performed, followed by
      hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS)
      operated in positive electrospray ionization (ESI) mode with multiple reaction
      monitoring (MRM) data acquisition. After method validation, assessing the
      prevalence of nicotine consumption in sport involved analysis of 2185 urine
      samples, accounting for 43 different sports. Concentrations distribution of major
      nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged
      from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest
      were detected in trace levels in 23.0% of urine specimens, with concentration
      levels corresponding to an exposure within the last three days for 18.3% of
      samples. Likewise, hypothesizing conservative concentration limits for active
      nicotine consumption prior and/or during sport practice (50 ng/mL for nicotine,
      cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide, cotinine
      N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3%
      amongst athletes. While this number may appear lower than the worldwide smoking
      prevalence of around 25%, focusing the study on selected sports highlighted more
      alarming findings. Indeed, active nicotine consumption in ice hockey, skiing,
      biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American
      football, wrestling and gymnastics was found to range between 19.0 and 55.6%.
      Therefore, considering the adverse effects of smoking on the respiratory tract
      and numerous health threats detrimental to sport practice at top level,
      likelihood of smokeless tobacco consumption for performance enhancement is
      greatly supported.

PMID- 21719222
TI  - [Campylobacter jejuni spondylodiscitis].

PMID- 21719223
TI  - Feasibility of MRI-guided high intensity focused ultrasound treatment for
      adenomyosis.
AB  - PURPOSE: To test the feasibility of MRI-guided high intensity focused ultrasound
      ablation for adenomyosis. MATERIALS AND METHODS: Patients with symptomatic
      adenomyosis were treated with MRI-guided high intensity focused ultrasound
      (MRIgHIFU). Under conscious sedation, MRIgHIFU was performed by a clinical MRI
      compatible focused ultrasound tumour therapeutic system (JM15100, Haifu(r)
      Technology Co. Ltd., Chongqing, China) which is combined with a 1.5 T MRI system
      (Magnetom Symphony, Siemens Healthcare, Erlangen, Germany). MRI was used to
      calculate the volume of the uterus and lesion. Non-perfused volume of the
      targeted lesions was evaluated immediately after MRIgHIFU. Patient symptoms were
      assessed using symptom severity score (SSS) and uterine fibroids symptoms and
      quality of life questionnaire (UFS-QOL). RESULTS: Ten patients with mean age of
      40.3+/-4 years with an average lesion size of 56.9+/-12.7 mm in diameter were
      treated. Non-perfused volume and the percentage of non-perfused volume obtained
      from contrast-enhanced T1 Magnetic resonance images immediately post-treatment
      were 66.6+/-49.4 cm3 and 62.5+/-21.6%, respectively. The mean SSS and UFS-QOL
      showed significant improvements of 25%, 16% and 25% at 3, 6 and 12 months follow
      up, respectively, to pre-treatment scores. No serious complications were
      observed. CONCLUSION: Based on the results from this study, MRIgHIFU treatment
      appears to be a safe and feasible modality to ablate adenomyosis lesion and
      alleviate its symptoms.

PMID- 21719224
TI  - Hepatocellular MR contrast agents: enhancement characteristics of liver
      parenchyma and portal vein after administration of gadoxetic acid in comparison
      to gadobenate dimeglumine.
AB  - PURPOSE: To investigate the enhancement characteristics of liver parenchyma and
      portal vein as well as the portal vein-to liver contrast in Gd-EOB-DTPA- and Gd
      BOPTA-enhanced abdominal MRI. MATERIALS AND METHODS: The local institutional
      review board approved this retrospective study. A total of 70 patients (30
      female, 40 male) without relevant liver disease underwent either Gd-EOB-DTPA
      enhanced (35 patients, dose 0.025 mmol/kg) or Gd-BOPTA-enhanced (35 patients,
      dose 0.1 mmol/kg) abdominal MRI. Signal-to-noise ratios (SNR) for the portal vein
      and the liver as well as portal vein-to-liver contrast-to-noise ratios (CNR) were
      calculated for three consecutive arterial phases, one portal venous phase and one
      delayed imaging phase. RESULTS: The liver SNR showed higher values for the Gd
      BOPTA group in the arterial and portal venous phases (statistically significant
      for the second and third arterial phase), while the liver SNR in the delayed
      phase was higher for the Gd-EOB-DTPA group. The portal venous SNR as well as the
      portal vein-to-liver CNR was higher in the Gd-BOPTA group in all imaging phases
      (statistically significant in all phases except for the first arterial phase).
      CONCLUSION: The enhancement of liver parenchyma and portal vein as well as the
      portal vein-to-liver contrast in the arterial and portal venous imaging phases
      were higher for patients receiving Gd-BOPTA compared with Gd-EOB-DTPA at the
      respective recommended doses. Gd-BOPTA might therefore enable better evaluation
      of the portal vein.

PMID- 21719225
TI  - Computational area measurement of orbital floor fractures: reliability, accuracy
      and rapidity.
AB  - OBJECTIVE: To evaluate the reliability, accuracy and rapidity of a specific
      computational method for assessing the orbital floor fracture area on a CT scan.
      METHOD: A computer assessment of the area of the fracture, as well as that of the
      total orbital floor, was determined on CT scans taken from ten patients. The
      ratio of the fracture's area to the orbital floor area was also calculated. The
      test-retest precision of measurement calculations was estimated using the
      Intraclass Correlation Coefficient (ICC) and Dahlberg's formula to assess the
      agreement across observers and across measures. The time needed for the complete
      assessment was also evaluated. RESULTS: The Intraclass Correlation Coefficient
      across observers was 0.92 [0.85;0.96], and the precision of the measures across
      observers was 4.9%, according to Dahlberg's formula .The mean time needed to make
      one measurement was 2 min and 39 s (range, 1 min and 32 s to 4 min and 37 s).
      CONCLUSION: This study demonstrated that (1) the area of the orbital floor
      fracture can be rapidly and reliably assessed by using a specific computer system
      directly on CT scan images; (2) this method has the potential of being routinely
      used to standardize the post-traumatic evaluation of orbital fractures.

PMID- 21719226
TI  - Development and validation of a GC/MS method for the determination of tadalafil
      in whole blood.
AB  - Tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor and it is used in the
      treatment of pulmonary arterial hypertension and erectile dysfunction. A
      sensitive and specific method is described for the determination of tadalafil in
      whole blood. Tadalafil and its internal standard (protriptyline) were isolated
      from the matrix by solid phase extraction, and were analyzed by gas
      chromatography/mass spectrometry (GC/MS) after derivatization by N,O
      bis(trimethylsilyl)-trifluoracetamide (BSTFA) with 1% trimethylchlorsilane
      (TMCS). Limits of detection and quantification for tadalafil were 0.70 and 2.00
      MUg/L, respectively. The calibration curve was linear between 2.00 and 500.0
      MUg/L, with a correlation coefficient higher than 0.991. The values obtained for
      intra- and inter-day accuracy was found to be between -10.5 to 8.5% and -4.2 to
      4.5%, respectively, while intra- and inter-day precision were less than 8.4 and
      11.2%, correspondingly. Absolute recovery was determined at three concentration
      levels and ranged from 92.1 to 98.9%. The proposed method is the first fully
      validated GC/MS method for the determination of tadalafil in whole blood and it
      can be routinely applied by toxicological laboratories, for pharmacokinetic
      studies, for therapeutic drug level monitoring or for the investigation of
      related forensic cases.

PMID- 21719227
TI  - Development of a validated liquid chromatographic method for determination of
      related substances of telmisartan in bulk drugs and formulations.
AB  - A simple and rapid reversed phase liquid chromatographic method for separation
      and determination of the related substances of telmisartan (TLM) was developed
      and validated. The chromatographic separation was achieved on Lichrospher RP-18
      column (250 * 4.6 mm, 5 MUm), using 20 mM ammonium acetate containing 0.1% (v/v)
      triethylamine (pH adjusted to 3.0 with trifluoroacetic acid) and acetonitrile as
      mobile phase at 25 degrees C. The detection was performed at 254 nm. The method
      was validated and found to be robust, precise, specific and linear between 0.37
      and 500 MUg/mL. The limits of detection and quantification of telmisartan were
      0.11 and 0.37 MUg/mL, respectively. The method was successfully applied to
      quantify related substances and assay of TLM in bulk drugs and commercial
      tablets. The related substances relate to a novel synthetic route and different
      from those A-H impurities reported by European Pharmacopeia.

PMID- 21719228
TI  - Spontaneous hemorrhage within the neck of a neurofibromatosis type 1 patient.
AB  - BACKGROUND: Spontaneous arterial bleeding in patients with type 1
      neurofibromatosis is uncommon. It can be fatal if not recognized and treated in a
      timely manner. OBJECTIVES: Diagnose and treat an uncommon complication in type 1
      neurofibromatosis. CASE REPORT: We report a patient with type 1 neurofibromatosis
      who bled spontaneously from a pseudoaneurysm arising from a branch of the left
      thyrocervical artery. The patient was successfully treated with endovascular
      therapy. CONCLUSION: Due to the high fragility of involved vessels in patients
      with type 1 neurofibromatosis, emergent angiography and endovascular therapy
      should be undertaken without delay, regardless of the presence or absence of
      contrast extravasation on computed tomography scan.

PMID- 21719229
TI  - Emergency department utilization among a cohort of HIV-positive injecting drug
      users in a Canadian setting.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-positive injection drug users
      (IDUs) are known to be at risk for multiple medical problems that may necessitate
      emergency department (ED) use; however, the relative contribution of HIV disease
      vs. injection-related complications has not been well described. OBJECTIVES: We
      examined factors associated with ED use among a prospective cohort of HIV
      positive IDUs in a Canadian setting. METHODS: We enrolled HIV-positive IDUs into
      a community-recruited prospective cohort study. We modeled factors associated
      with the time to first ED visit using Cox regression to determine factors
      independently associated with ED use. In sub-analyses, we examined ED diagnoses
      and subsequent hospital admission rates. RESULTS: Between December 5, 2005 and
      April 30, 2008, 428 HIV-positive IDUs were enrolled, among whom the cumulative
      incidence of ED use was 63.7% (95% confidence interval [CI] 59.1-68.3%) at 12
      months after enrollment. Factors independently associated with time to first ED
      visit included: unstable housing (hazard ratio [HR] 1.5; 95% CI 1.1-2.0) and
      reporting being unable to obtain needed health care services (HR 2.2; 95% CI 1.2
      4.1), whereas CD4 count and viral load were non-significant. Skin and soft tissue
      infections accounted for the greatest proportion of ED visits (17%). Of the 2461
      visits to the ED, 419 (17%) were admitted to the hospital. CONCLUSIONS: High
      rates of ED use were observed among HIV-positive IDUs, a behavior that was
      predicted by unstable housing and limited access to primary care. Factors other
      than HIV infection seem to be driving ED use among this population in the post
      highly active antiretroviral therapy era.

PMID- 21719230
TI  - Unexpected late rise in plasma acetaminophen concentrations with change in risk
      stratification in acute acetaminophen overdoses.
AB  - BACKGROUND: The acetaminophen risk analysis nomogram is used to predict
      hepatotoxicity risk in acute acetaminophen overdose based on a single plasma
      acetaminophen concentration (PAC) measured between 4 and 24 h after ingestion.
      There are case reports of patients with acute overdoses of acetaminophen
      combination products in whom a toxic PAC occurred later after an initial non
      toxic PAC at approximately 4 h. OBJECTIVES: The objective was to describe
      patients who had an initial non-toxic PAC and a subsequent toxic PAC. METHODS: A
      poison center's database was searched for records in which patients were
      administered N-acetylcysteine. Cases were included if they involved an acute
      overdose of an acetaminophen-containing product with at least 2 plottable PACs,
      the first of which was obtained at least 4 h after ingestion and was below the
      treatment line on the nomogram with a subsequent toxic PAC. Data were analyzed
      for doses, timed PACs, specific acetaminophen preparation, coingestants,
      activated charcoal administration, and clinical effects. RESULTS: Twenty patients
      were included. Thirteen patients ingested combination products. All patients
      experienced vomiting, neurologic, or cardiovascular effects at presentation or
      before obtaining the second PAC. Two patients developed hepatotoxicity, one of
      which died from the complications of acetaminophen-induced hepatotoxicity.
      CONCLUSION: The nomogram fails to predict toxicity based on a single PAC in a
      small subset of patients.

PMID- 21719231
TI  - Fetal outcomes in first trimester pregnancies with an indeterminate ultrasound.
AB  - BACKGROUND: Pregnant women commonly present to the Emergency Department (ED) for
      evaluation during their first trimester. These women have many concerns, one of
      which is the viability of their pregnancy and the probability of miscarriage.
      STUDY OBJECTIVES: We sought to determine fetal outcomes of women with an
      indeterminate ultrasound who present to the ED during the first trimester of
      pregnancy. METHODS: A retrospective analysis of consecutive ED patient encounters
      from December 2005 to September 2006 was performed to identify patients who were
      pregnant and who had an indeterminate transvaginal ultrasound performed by an
      emergency physician or through the Radiology Department during their ED visit.
      Demographic data, obstetric/gynecologic history, and presenting symptoms were
      recorded onto a standardized patient chart template designed to be used for any
      first trimester pregnancy. Outcomes (spontaneous abortion, ectopic pregnancy, and
      20-week gestation) were determined via computerized medical records. RESULTS:
      During the study timeframe, a total of 1164 patients were evaluated in the ED
      during the first trimester of their pregnancy; 359 patients (30.8%) met inclusion
      criteria and had a diagnosis of indeterminate ultrasound. Outcome data were
      obtained for 293 patients. Carrying the pregnancy to >=20 weeks occurred in 70
      patients (23.9%). Spontaneous abortion occurred in 193 women (65.9%), and 30
      women (10.2%) were treated for an ectopic pregnancy. Total fetal loss incidence
      was 89.2% in patients presenting with any vaginal bleeding, compared to 34.7% in
      patients with pain only. CONCLUSION: Indeterminate ultrasounds in the setting of
      first trimester symptomatic pregnancy are indicative of poor fetal outcomes.
      Vaginal bleeding increased the risk of fetal loss. These data will assist
      emergency physicians in counseling women in the ED who are found to have an
      indeterminate ultrasound.

PMID- 21719232
TI  - Narcotic bowel syndrome.
AB  - BACKGROUND: Narcotic bowel syndrome is characterized by chronic or recurrent
      abdominal pain associated with escalating doses of narcotic pain medications. It
      may occur in as many as 4% of all patients taking opiates, and yet few physicians
      are aware that the syndrome exists. OBJECTIVES: The objectives of this case
      report are to raise awareness of narcotic bowel syndrome among emergency
      physicians, as well as review the clinical features, diagnosis, pathophysiology,
      and emergency department (ED) management of the syndrome. CASE REPORT: We report
      a case of narcotic bowel syndrome diagnosed in a 24-year-old woman after > 1 year
      of ED visits for recurrent abdominal pain of unknown origin. CONCLUSIONS: It is
      particularly important for emergency physicians to be familiar with this
      syndrome, as many patients with narcotic bowel syndrome seek evaluation and
      treatment in the ED. Although the diagnosis is unlikely to be made in the ED,
      timely referral for evaluation of this syndrome may help patients to receive
      definitive treatment for their recurrent and chronic pain.

PMID- 21719233
TI  - Nummular eczema.

PMID- 21719234
TI  - Effect of sitting vs. standing on perception of provider time at bedside: a pilot
      study.
AB  - OBJECTIVE: Patients commonly perceive that a provider has spent more time at
      their bedside when the provider sits rather than stands. This study provides
      empirical evidence for this perception. METHODS: We conducted a prospective,
      randomized, controlled study with 120 adult post-operative inpatients admitted
      for elective spine surgery. The actual lengths of the interactions were compared
      to patients' estimations of the time of those interactions. RESULTS: Patients
      perceived the provider as present at their bedside longer when he sat, even
      though the actual time the physician spent at the bedside did not change
      significantly whether he sat or stood. Patients with whom the physician sat
      reported a more positive interaction and a better understanding of their
      condition. CONCLUSION: Simply sitting instead of standing at a patient's bedside
      can have a significant impact on patient satisfaction, patient compliance, and
      provider-patient rapport, all of which are known factors in decreased litigation,
      decreased lengths of stay, decreased costs, and improved clinical outcomes.
      PRACTICE IMPLICATIONS: Any healthcare provider may have a positive effect on
      doctor-patient interaction by sitting as opposed to standing during a hospital
      follow-up visit.

PMID- 21719235
TI  - Illness beliefs, treatment beliefs and information needs as starting points for
      patient information--evaluation of an intervention for patients with chronic back
      pain.
AB  - OBJECTIVE: The objective of the study was to evaluate an intervention which
      applied the extended Common Sense Model to the provision of information about
      illness and treatment during inpatient rehabilitation for patients with chronic
      back pain. METHODS: The intervention was evaluated in a sequential control group
      design (control group N=105; intervention group N=96). Changes with respect to
      illness and treatment beliefs, satisfaction with information, and health status
      at the end of rehabilitation were selected as outcome measures. Analyses of
      covariance were used to assess differences between control and intervention
      group. RESULTS: Significant time-by-group interactions were shown for causal
      beliefs, personal control, satisfaction with information about illness and
      rehabilitation, and for general health. All time-by-group interactions indicated
      superiority of the intervention group. CONCLUSION: The intervention group
      assessed their back pain as personally controllable and their information needs
      at the end of rehabilitation as being met to a greater extent than did patients
      who received care as usual. PRACTICE IMPLICATIONS: The extended Common Sense
      Model seems promising as a frame for discussing illness and treatment perceptions
      as well as information needs in patients with chronic back pain.

PMID- 21719236
TI  - A questionnaire on treatment satisfaction and disease specific knowledge among
      patients with acute coronary syndrome. II: Insights for patient education and
      quality improvement.
AB  - OBJECTIVE: Secondary prevention for coronary heart disease is achieved by
      pharmaceutical control of risk factors and patients' own self management
      behaviour. To comply with longterm treatment patients need sufficient knowledge
      of their condition and should be satisfied with acute care. Therefore a
      questionnaire measuring both issues was constructed. METHODS AND RESULTS: Latent
      class analysis applied in a sample of over 2000 patients suffering from acute
      coronary syndrome revealed 4 configurative patterns of knowledge and 5 distinct
      patterns of (dis-)satisfaction. Nearly 50% of all patients displayed insufficient
      knowledge upon discharge. Deficits clustered around misinformation on necessary
      lifestyle changes versus dysfunctional strategies for future emergency
      situations. Satisfaction and disease specific knowledge were interrelated in
      complex patterns. CONCLUSIONS: Disease specific knowledge and satisfaction with
      treatment proved to be psychometrically valid indicators of the quality of the
      treatment process that might also have an impact on outcome. PRACTICE
      IMPLICATIONS: A validated questionnaire is ready for routine administration after
      discharge of patients with acute coronary syndrome from acute hospital care.
      Patient education efforts and quality improvement in treatment centres might be
      effectively monitored using this questionnaire.

PMID- 21719237
TI  - A questionnaire on treatment satisfaction and disease specific knowledge among
      patients with acute coronary syndrome. I: Are treatment satisfaction and disease
      specific knowledge continuous latent traits?
AB  - OBJECTIVE: To assess psychometric properties of a questionnaire covering
      treatment satisfaction and disease-specific knowledge among patients discharged
      after treatment for acute coronary syndrome. METHODS: Comparative scaling of the
      questionnaire using latent class analysis (LCA) and exploratory factor analysis
      (EFA) in a consecutive sample of 2015 patients. RESULTS: LCA revealed four
      qualitatively differing patterns of patients' knowledge and five distinct
      patterns of treatment satisfaction. EFA for patients' knowledge identified four
      uncorrelated "dimensions". Patient satisfaction was scored in a two-factor
      solution despite proven heterogeneity of persons. CONCLUSIONS: LCA was helpful to
      identify classes of patients that cannot be scaled according to a latent trait
      model. PRACTICE IMPLICATIONS: Specific patterns of insufficient disease-specific
      knowledge and satisfaction requiring specific interventions became visible.

PMID- 21719238
TI  - [Imprecision of vancomycin prepared for intravenous administration at the bedside
      in a neonatal intensive care unit].
AB  - In pediatric units, most of the intravenous medications are prepared by the
      attending nurse at the bedside that can be affected by an error margin, so can be
      imprecise. Despite the possible consequences of imprecise medications
      administration, published studies on the topic are scarce. The main objective of
      this study was to measure the difference between the prescribed vancomycine
      concentration and the actual concentration measured in the medication
      administered to the patient. The secondary objective was to determine which step
      in the preparation was linked to the difference in concentrations. It was a
      prospective study, setting in a pediatric and neonatal university hospital
      intensive care unit. Over a 3-month period, an aliquot from every preparation for
      continuous infusion of vancomycin, made at the bedside by a nurse, was collected
      and the modalities of the preparation noted. Vancomycin concentration was
      measured by high performance liquid chromatography. Sixty-four preparations,
      accounting for 24 patients (gestationnal age: 67 +/- 75 weeks, weigh: 4.8 +/- 6.5
      kg) were included. Vancomycin concentrations ranged from 3.33 to 60.0mg/mL.
      Measured concentration were in mean 7% smaller than prescribed concentration
      (P<10(-3)), with a large confidence interval (75.8%-120.4% of the prescribed
      concentration). Imprecision the preparations was much higher than this admitted
      for manufactured preparation. We could not highlight any factor related to the
      difference in concentrations, but one third of the preparation did not respect
      all the ISO 7886 standards for syringes use. Bedside vancomycin preparations,
      like preparations for other molecules, are far more imprecise than industrial
      intravenous medications. Our results urge that all pediatric intravenous
      medications should be made only by manufacturers or pharmacists. However, it also
      urged clinical studies, in parallel to pharmacodynamic and pharmacokinetic
      studies, to make intravenous treatments as accurate as they should be.

PMID- 21719239
TI  - [Sugammadex and renal failure: a case report].
AB  - We report a case of delayed rocuronium-induced deep block antagonization with
      sugammadex, thus requiring a total of three injections and a cumulative dose of
      12 mg/kg over a 30 min period. The patient was an emergency case with full
      stomach that had required a rapid sequence induction. Because of hyperkaliemia
      due to an acute renal failure, rocuronium was preferred to succinylcholine. Use
      of sugammadex in the acute renal failure context is discussed.

PMID- 21719240
TI  - [Survey on anaesthetic practices for electroconvulsivotherapy in French
      university hospitals].
AB  - OBJECTIVES: To evaluate the anaesthetic management of electroconvulsive therapy
      (ECT) in French university hospitals. STUDY DESIGN: National survey in university
      hospitals by mail. MATERIALS AND METHODS: An email was sent to heads of
      department of anaesthesiology in French university hospitals to identify a
      referent practitioner, which we then sent a computerized quiz. The questions were
      about the volume and organization of the activity, pre-, per- and post
      anaesthetic management of patients undergoing ECT. RESULTS: Of the 33 sites
      performing ECT, 28 (85%) responded. The anaesthesia consultation was systematic
      at least 48 hours before the start of treatment but the preanaesthetic visit was
      performed in 32% of the centers. A routine electrocardiogram was performed in 89%
      of patients. In four centers (25%), neuromuscular blockade was not systematic.
      Propofol was the agent most widely used (82%) and etomidate and thiopental in 11%
      and 7% respectively. In two centers, practitioners did not report using oral
      protection. The psychiatrist was present in 71% of cases. The
      electroencephalogram was continuously recorded in 45% of the centers. CONCLUSION:
      The recommendations remain valid while old and may be updated. They are not
      always followed by the teams. Continuing medical education should be promoted to
      a better understanding of the factors interfering between anesthesia and ECT.

PMID- 21719241
TI  - [Use of the Airtraq by inexperienced physicians supervised during a series of
      tracheal intubation in adult patient with anticipated difficult airway].
AB  - INTRODUCTION: The Airtraq optical laryngoscope (Vygon, Ecouen, France) is a new
      intubation device designed to provide a view of the glottis without alignment of
      the oral, pharyngeal and laryngeal axes. In recent literature, the efficiency of
      the Airtraq even in difficult intubation and its short learning curve were
      characterized. The goal of our study is to evaluate Airtraq efficiency when use
      by inexperienced physicians in anticipated difficult intubation adult patients.
      METHODS: The patients showing at least one of the four difficult intubation
      predictors (history of difficult intubation, thyromental distance less than 60mm,
      mouth opening less than 35 mm and Mallampati class 3 or 4 were included. Before
      induction of anaesthesia, the inexperienced physicians participating the study
      received a short oral formation on the use of the Airtraq. For each intubation
      manoeuvres, the participant were supervised by an expert in Airtraq handling. The
      Cormack and Lehane grade of direct laryngoscopy view, the duration times to best
      glottis view and to intubate the trachea, the success or failure of tracheal
      intubation, the drop in arterial oxygen saturation of below 95%, the need for
      external manipulation, and the difficulties met by the operators were noted.
      RESULTS: Twenty patients were included over a month period. Thirteen had a
      history of difficult intubation, eight a thyromental distance less than 60mm,
      nine a mouth opening less than 35 mm and 12 patients were classified as
      Mallampati IV. The success rate of tracheal intubation with the Airtraq
      laryngoscope was 80%. Times to best glottis view and to complete tracheal
      intubation were 28 and 47 s, respectively. Four tracheal intubation failures were
      encountered. The LMA Fastrach and the flexible fiberoscope were used respectively
      in one and three patients. DISCUSSION: In the majority of the cases, the
      insertion of the Airtraq, the visualization of the glottis and the subsequent
      intubation were easy and rapid, without arterial oxygen desaturation. However,
      the four tracheal intubation failures associated with prolonged tracheal
      intubation times in some patients highlight the fact that the Airtraq
      laryngoscope requires a clinical training process particularly in case of
      anticipated difficult airway management situations.

PMID- 21719242
TI  - [Subclavian artery rupture after road crash: many similitaries].
AB  - INTRODUCTION: Traumatic Subclavian Arterial Ruptures (TSCAR) are rare and with a
      poor prognosis. The aim of this study was to describe the epidemiological data
      and the medical charts of the initial care of each patient suffering a TSCAR
      following a traffic accident. METHODS: Using the register of the road crash in
      the Rhone department (France) that records every casualty using the AIS codes, we
      retrospectively reviewed the prehospital and intrahospital medical, biological
      and radiological charts of every patient. Follow-up was obtained at day 60 post
      trauma. RESULTS: Among the 1181 severe traumatic injuries, five casualties have
      been recorded in the register with a TSCAR (0.4%). Four of the five patients died
      in an early dramatic fatal hemorrhagic shock. Similarities between casualties
      were observed for patients still alive at hospital arrival that associate 1) a
      two-wheel motorized rider (2-WMR) crashing without antagonist 2) a severe
      polytraumatism including thoracic and 3) orthopaedic lesions; 4) clinical and
      biological signs of a severe haemorrhagic shock; 5) radiological signs of
      scapulothoracic dissociation. CONCLUSION: TSCAR are rare with a high mortality.
      We recommend improving the early care by the recognition of the triad associating
      early severe shock, polytraumatism (thorax and superior limb) and radiological
      signs evocating scapulothoracic dissociation in a 2-WMR. These signs must lead to
      the operating theatre as fast as possible in association with early massive
      transfusions.

PMID- 21719243
TI  - Transcriptional regulation of the chemokine co-receptor CCR5 by the cAMP/PKA/CREB
      pathway.
AB  - The cyclic adenosine monophosphate (cAMP)-dependent signaling pathway directs the
      expression of several genes involved in diverse neuroendocrine, immune,
      metabolic, and developmental pathways. The primary effectors of this pathway are
      members of the cAMP response element binding (CREB) family of transcription
      factors, in particular the CREB-1 and cAMP response element modulator (CREM).
      Both these genes encode alternative splice variants that serve as activators or
      repressors in a context- and position-specific manner. Although the beta
      chemokine receptor CC chemokine receptor 5 (CCR5) has been identified on
      progenitor cells in the bone marrow, the regulatory mechanisms orchestrating its
      expression are not fully understood. Previous reports have identified putative
      cAMP response elements in the CCR5 promoter and have described a suppressive role
      of cAMP in CCR5 expression. In this study, the CD34+CD4+CCR5+ human bone marrow
      progenitor cell line TF-1 was used to investigate the detailed kinetics of CCR5
      transcription in response to the elevation of intracellular cAMP levels and the
      underlying molecular events. We hypothesize that CCR5 transcription follows an
      asymmetrical sinusoidal pattern in TF-1 cells that parallels a protein kinase A
      dependent alternating change in the ratio of activator pCREB-1-alpha,Delta to
      repressor pCREM-alpha,beta isoforms. However, elevated CCR5 mRNA levels do not
      correlate with enhancement in infectivity with respect to the R5 human
      immunodeficiency virus type 1 (HIV-1) strain. Our results lend critical insight
      into the precise mechanism governing the cAMP-CCR5 axis in progenitor cells and
      pose interesting questions regarding its functional role in HIV-1 infection.

PMID- 21719244
TI  - A new model of rectal cancer with regional lymph node metastasis allowing in vivo
      evaluation by imaging biomarkers.
AB  - OBJECT: The work is aimed to develop a murine model of rectal cancer, which could
      be used to monitor lymph node metastasis development by magnetic resonance
      imaging (MRI) and optical imaging (OI) techniques. SUBJECTS AND METHODS: Ht-29
      cancer cells were directly injected into the submucosal layer of the rectum of
      athymic nude mice using trans-anal rectal cancer cell injection (TARCI). Thirty
      six mice were inoculated with 10*10(5) cells and five mice were treated with
      sterile phosphate buffer solution. One to 4 weeks after cell injection, tumor
      growth was evaluated in vivo using T2-weighted MRI at 4.7T. A further group of
      animal (n=6) treated with ht-29_luc cells, with the same protocol, was monitored
      by optical imaging. In both groups, the presence of the primary tumor and of
      lymph nodes metastasis was confirmed by histology. RESULTS: In all animals,
      primary tumors were detectable by MRI, 1 week from TARCI. After 4 weeks primary
      tumors showed a mean longitudinal diameter of about 2cm. All animals developed
      regional lymph node metastases. Others organs (e.g. lung or liver) were not
      affected. In fat-suppressed, T2-weighted MRI, lymph nodes appeared as small areas
      characterized by hyper-intense signal compared to muscle. OI permitted evaluation
      of the primary tumor growth in perineal region. CONCLUSIONS: TARCI of ht-29 cells
      into the rectum of nude mice is a feasible way to obtain a easily reproducible
      model of regional lymph node metastases could be monitored by magnetic resonance
      and optical imaging techniques.

PMID- 21719245
TI  - Inhibition of cyclooxygenase-2 promotes the stimulatory action of adenosine A3
      receptor agonist on hematopoiesis in sublethally gamma-irradiated mice.
AB  - Mouse hematopoiesis, suppressed by a sublethal dose of ionizing radiation, was
      the target for combined therapy with a cyclooxygenase-2 (COX-2) inhibitor
      meloxicam and an adenosine A3 receptor agonist IB-MECA. The drugs were
      administered in an early postirradiation treatment regimen: meloxicam was given
      in a single dose 1hour after irradiation, IB-MECA in two doses 24 and 48hours
      after irradiation. Treatment-induced changes in several compartments of
      hematopoietic progenitor and precursor cells of the bone marrow were evaluated on
      day 3 after irradiation. Values of hematopoietic progenitor cells for
      granulocytes/macrophages and erythrocytes (GM-CFC and BFU-E, respectively), as
      well as those of proliferative granulocytic cells were found to be significantly
      higher in the mice treated with the drug combination in comparison to irradiated
      controls and attained the highest increase factors of 1.6, 1.6, and 2.6,
      respectively. The study emphasizes the significance of the combined treatment of
      suppressed hematopoiesis with more agents. Mechanisms of the action of the
      individual compounds of the studied drug combination and of their joint operation
      are discussed.

PMID- 21719246
TI  - Expression of organic anion-transporting polypeptides 1B1 and 1B3 in ovarian
      cancer cells: relevance for paclitaxel transport.
AB  - PURPOSE: Ovarian cancer remains a deadly malignancy because most patients develop
      recurrent disease that is resistant to chemotherapy. Organic anion-transporting
      polypeptides (OATPs) mediate the uptake of clinically important drugs thereby
      effecting intracellular drug accumulation. In this study, we investigated whether
      OATPs may also contribute to paclitaxel transport in estrogen-responsive and
      estrogen-independent ovarian carcinoma cell lines and tumor tissue. METHODS:
      Expression of all 11 human OATPs in human ovarian cancer tissue samples and in
      the ovarian carcinoma cell lines OVCAR-3 and SK-OV-3 was investigated using real
      time RT-PCR. Kinetic analysis of paclitaxel uptake was characterized in both cell
      lines and in OATP-transfected Xenopus laevis oocytes. Cytotoxicity of paclitaxel
      in OVCAR-3, SK-OV-3 and OATP1B1- and OATP1B3-transfected SK-OV-3 cells was
      performed using the CellTiter-Glo assay. RESULTS: OATP1B1 and OATP1B3 are active
      paclitaxel transporters in transfected X. laevis oocytes. Real-time RT-PCR
      analysis revealed expression of both OATPs in human ovarian cancer tissue
      specimens and in cancer cell lines. The higher mRNA levels for OATP1B1 and
      OATP1B3 found in SK-OV-3 cells correlated with higher initial uptake rates for
      paclitaxel. In addition, cytotoxicity studies with OATP1B1- and OATP1B3
      transfected SK-OV-3 cells demonstrated lower IC(50) values compared to cells
      transfected with the empty vector. CONCLUSIONS: Our results revealed OATP1B1 and
      OATP1B3 as high-affinity paclitaxel transporters expressed in ovarian cancer cell
      lines and tumor tissues, suggesting a role for these polypeptides in the
      disposition of paclitaxel during therapy.

PMID- 21719247
TI  - Synthesis of cyanopyridine and pyrimidine analogues as new anti-inflammatory and
      antimicrobial agents.
AB  - A new series of substituted benzylidene acetophenone (Ia-Ih), 2-amino-4, 6-
      substituted diphenylpyridine-3-carbonitrile (IIa-IIh) and 4, 6-substituted
      diphenylpyrimidin-2-amine (IIId-IIIg) were synthesized and evaluated for anti
      inflammatory and antimicrobial activities. Four compounds (Ie, If, IIh and IIId)
      have shown good anti-inflammatory activity when compared to standard drug
      indomethacin. Two compound (Ie and IIh) displayed significant activity against
      gram -ve bacteria (E. Coli) and three compounds (IId, IIf and IIIh) displayed
      good activity against gram +ve bacteria (S. aureus) on comparison with the
      standard drug ofloxacin.

PMID- 21719248
TI  - [Cardiovascular disease and aircraft transportation: specificities and issues].
AB  - With the development of air transport and travel to distant destinations, the
      number of passengers and elderly passengers on board increases each year. In this
      population, cardiovascular events are a major concern. Among medical incidents
      occurring in-flight they are second-ranked (10%) behind gastrointestinal
      disorders (25%). Their occurrence may involve life-threatening events and require
      resuscitation, difficult to perform during flight or in a precarious health
      environment. Coronary heart disease and pulmonary thromboembolic disease are the
      most serious manifestations. They are the leading cause of hospitalization in a
      foreign country and sudden cardiac death occurring during or subsequent to the
      flight. Their occurrence is explained on aircraft by hypoxia, hypobaria and
      decreased humidity caused by cabin pressurization and upon arrival by a different
      environmental context (extreme climates, tropical diseases). Moreover, the
      occurrence of a cardiovascular event during flight can represent for the air
      carrier a major economic and logistic problem when diversion occurred.
      Furthermore, the liability of the practitioner passenger could be involved
      according to airlines or to the country in which the aircraft is registered. In
      this context, cardiovascular events during aircraft transportation can be easily
      prevented by identifying high risk patients, respect of cardiovascular
      indications to travel, the implementation of simple preventive measures and
      optimization of medical equipment in commercial flights.

PMID- 21719249
TI  - The role of transbronchial biopsy in the diagnosis of diffuse parenchymal lung
      diseases: pro.

PMID- 21719250
TI  - The effectiveness of patient-family carer (couple) intervention for the
      management of symptoms and other health-related problems in people affected by
      cancer: a systematic literature search and narrative review.
AB  - CONTEXT: Cancer is widely acknowledged to impact on the whole family. Yet, we do
      not know if there is benefit (or harm) from patient-family carer interventions in
      the context of cancer care. OBJECTIVES: To report a systematic search for and
      narrative review of patient-family carer interventions tested in the context of
      cancer care for effect on symptoms and other health-related problems in patients
      and/or their family members. METHODS: A systematic literature search was carried
      out using Cochrane principles. Searches were of MEDLINE, EMBASE, PsycINFO, and
      CINAHL databases for reported trials of patient-family carer focused
      interventions. Outcomes of interest were health indicators; measures of physical,
      psychological, social, and quality-of-life status of the patient and/or family
      member(s). Limits were English language; 1998 to March 2010; and adults. Relevant
      information was extracted, quality assessed using the Cochrane Collaboration's
      tool for assessing risk of bias, and presented as a narrative synthesis (meta
      analysis was not appropriate). RESULTS: The review found no empirically tested
      interventions for family groups (patient and two or more family members), but 22
      interventions for patient-family carer partnerships (couple interventions) tested
      in 23 studies and reported in 27 publications. Recruitment and attrition were
      problematic in these studies, limiting the reliability and generalizability of
      their results. CONCLUSION: In the trials of cancer couple interventions included
      in the review, a pattern emerged of improvement in the emotional health of cancer
      patients and their carers when the intervention included support for the patient
      family carer relationship. Further investigation is warranted.

PMID- 21719251
TI  - Reliable prediction intervals with regression neural networks.
AB  - This paper proposes an extension to conventional regression neural networks (NNs)
      for replacing the point predictions they produce with prediction intervals that
      satisfy a required level of confidence. Our approach follows a novel machine
      learning framework, called Conformal Prediction (CP), for assigning reliable
      confidence measures to predictions without assuming anything more than that the
      data are independent and identically distributed (i.i.d.). We evaluate the
      proposed method on four benchmark datasets and on the problem of predicting Total
      Electron Content (TEC), which is an important parameter in trans-ionospheric
      links; for the latter we use a dataset of more than 60000 TEC measurements
      collected over a period of 11 years. Our experimental results show that the
      prediction intervals produced by our method are both well calibrated and tight
      enough to be useful in practice.

PMID- 21719252
TI  - Divergence measures and a general framework for local variational approximation.
AB  - The local variational method is a technique to approximate an intractable
      posterior distribution in Bayesian learning. This article formulates a general
      framework for local variational approximation and shows that its objective
      function is decomposable into the sum of the Kullback information and the
      expected Bregman divergence from the approximating posterior distribution to the
      Bayesian posterior distribution. Based on a geometrical argument in the space of
      approximating posteriors, we propose an efficient method to evaluate an upper
      bound of the marginal likelihood. Moreover, we demonstrate that the variational
      Bayesian approach for the latent variable models can be viewed as a special case
      of this general framework.

PMID- 21719253
TI  - Estimating exogenous variables in data with more variables than observations.
AB  - Many statistical methods have been proposed to estimate causal models in
      classical situations with fewer variables than observations. However, modern
      datasets including gene expression data increase the needs of high-dimensional
      causal modeling in challenging situations with orders of magnitude more variables
      than observations. In this paper, we propose a method to find exogenous variables
      in a linear non-Gaussian causal model, which requires much smaller sample sizes
      than conventional methods and works even under orders of magnitude more variables
      than observations. Exogenous variables work as triggers that activate causal
      chains in the model, and their identification leads to more efficient
      experimental designs and better understanding of the causal mechanism. We present
      experiments with artificial data and real-world gene expression data to evaluate
      the method.

PMID- 21719254
TI  - The value of three-dimensional echocardiography derived mitral valve parametric
      maps and the role of experience in the diagnosis of pathology.
AB  - BACKGROUND: Accurate segmental mitral valve (MV) analysis is essential for
      surgical planning. Although real-time three-dimensional (3D) transesophageal
      echocardiography has improved the ability to visualize the MV, accurate
      localization of MV pathology from 3D transesophageal echocardiographic images
      still remains experience dependent. Three-dimensional parametric maps of the MV
      obtained from these images further simplify the visualization of MV anatomy. The
      aims of this study were to examine whether 3D parametric maps of the MV could
      improve the diagnostic accuracy in localizing pathology and to determine their
      usefulness for readers with different levels of training. METHODS: Five novice
      (American Society of Echocardiography [ASE] level 2), three intermediate-level
      (ASE level 3; <500 MV cases), and two expert (ASE level 3; >500 MV cases) readers
      interpreted MV segmental anatomy in 50 patients (30 with degenerative MV disease,
      20 with normal MVs). All readers reviewed two-dimensional and 3D transesophageal
      echocardiographic and 3D parametric maps at sequential weekly sessions. The
      results were compared with surgical findings. RESULTS: Expert readers were the
      most accurate irrespective of image type. Novice readers were the least accurate
      and commonly misinterpreted P2 and P3 scallops. Their accuracy was highest when
      interpreting 3D parametric maps (from 87% with two-dimensional transesophageal
      echocardiography to 92%). Intermediate readers' accuracy fell between the other
      two groups irrespective of image type and showed no change with the use of
      parametric maps. CONCLUSIONS: This is the first study to show that the
      interpretation of 3D parametric maps improves the accuracy of localization of MV
      pathology by novice readers. Therefore, parametric maps should be used routinely
      by less experienced readers during the assessment of degenerative MV disease.

PMID- 21719255
TI  - Tei index in fabry disease.
AB  - BACKGROUND: Systolic and diastolic dysfunction of the left ventricle are present
      in patients with cardiac involvement in Fabry disease. The aim of this study was
      to investigate the diagnostic value of the Tei index, a marker for combined
      diastolic and systolic function, in patients with Fabry disease. METHODS: A total
      of 66 consecutive patients with genetically confirmed Fabry disease were included
      in this study. Standard echocardiography, including the Tei index, and magnetic
      resonance imaging were performed. Patients were followed for 2.9 +/- 1.9 years;
      56 patients received enzyme replacement therapy, and 10 patients had natural
      history follow-up. Patients were subdivided into three groups: (1) those without
      cardiac involvement, (2) those with left ventricular (LV) hypertrophy and without
      late enhancement on magnetic resonance imaging, and (3) those with late
      enhancement on magnetic resonance imaging. RESULTS: The Tei index was
      significantly higher in the groups 2 (0.56 +/- 0.10) and 3 (0.60 +/- 0.16)
      compared with patients without cardiac involvement (0.44 +/- 0.10) (P < .001).
      All patients with Tei indexes > 0.64 showed signs of cardiomyopathy. In contrast,
      ejection fractions were normal in all three patient groups and therefore not
      useful for the detection of cardiac involvement. A significant positive
      correlation was observed between LV wall thickness and the Tei index in the
      complete patient cohort. Moreover, receiver operating characteristic analysis
      revealed a large area under the curve for Tei index and hypertrophy, while the
      area under the curve for fibrosis was small. The Tei index remained unchanged in
      the natural history and enzyme replacement therapy groups during follow-up.
      CONCLUSIONS: In this cohort, the Tei index was of limited value to detect
      myocardial fibrosis and monitor enzyme replacement therapy. However, the
      progression of cardiomyopathy toward LV hypertrophy seems to be paralleled by
      global functional impairment, which can be assessed by the Tei index but not by
      ejection fraction. Thus, the Tei index seems to be a global parameter that can
      detect LV functional reduction in patients with Fabry disease.

PMID- 21719256
TI  - Quick detection of brain tumors and edemas: a bounding box method using symmetry.
AB  - A significant medical informatics task is indexing patient databases according to
      size, location, and other characteristics of brain tumors and edemas, possibly
      based on magnetic resonance (MR) imagery. This requires segmenting tumors and
      edemas within images from different MR modalities. To date, automated brain tumor
      or edema segmentation from MR modalities remains a challenging, computationally
      intensive task. In this paper, we propose a novel automated, fast, and
      approximate segmentation technique. The input is a patient study consisting of a
      set of MR slices, and its output is a subset of the slices that include axis
      parallel boxes that circumscribe the tumors. Our approach is based on an
      unsupervised change detection method that searches for the most dissimilar region
      (axis-parallel bounding boxes) between the left and the right halves of a brain
      in an axial view MR slice. This change detection process uses a novel score
      function based on Bhattacharya coefficient computed with gray level intensity
      histograms. We prove that this score function admits a very fast (linear in image
      height and width) search to locate the bounding box. The average dice
      coefficients for localizing brain tumors and edemas, over ten patient studies,
      are 0.57 and 0.52, respectively, which significantly exceeds the scores for two
      other competitive region-based bounding box techniques.

PMID- 21719257
TI  - Dual-modality brain PET-CT image segmentation based on adaptive use of functional
      and anatomical information.
AB  - Dual medical imaging modalities, such as PET-CT, are now a routine component of
      clinical practice. Medical image segmentation methods, however, have generally
      only been applied to single modality images. In this paper, we propose the dual
      modality image segmentation model to segment brain PET-CT images into gray
      matter, white matter and cerebrospinal fluid. This model converts PET-CT image
      segmentation into an optimization process controlled simultaneously by PET and CT
      voxel values and spatial constraints. It is innovative in the creation and
      application of the modality discriminatory power (MDP) coefficient as a weighting
      scheme to adaptively combine the functional (PET) and anatomical (CT) information
      on a voxel-by-voxel basis. Our approach relies upon allowing the modality with
      higher discriminatory power to play a more important role in the segmentation
      process. We compared the proposed approach to three other image segmentation
      strategies, including PET-only based segmentation, combination of the results of
      independent PET image segmentation and CT image segmentation, and simultaneous
      segmentation of joint PET and CT images without an adaptive weighting scheme. Our
      results in 21 clinical studies showed that our approach provides the most
      accurate and reliable segmentation for brain PET-CT images.

PMID- 21719258
TI  - The effect of emotional context on facial emotion ratings in schizophrenia.
AB  - Individuals with schizophrenia show deficits both in facial emotion recognition
      and context processing (Kohler, C.G., Walker, J.B., Martin, E.A., Healey, K.M.,
      Moberg, P.J., 2010. Facial emotion perception in schizophrenia: a meta-analytic
      review. Schizophr. Bull. 36, 1009-1019). Recent evidence suggests context
      information can affect facial emotion recognition (Aviezer, H., Bentin, S.,
      Hassin, R.R., Meschino, W.S., Kennedy, J., Grewal, S., Esmail, S., Cohen, S.,
      Moscovitch, M., 2009. Not on the face alone: perception of contextualized face
      expressions in Huntington's disease. Brain 132, 1633-1644). Thus, individuals
      with schizophrenia may have deficits in facial emotion processing, at least in
      part, due to impairments in processing context information (Green, M.J., Waldron,
      J.H., Coltheart, M., 2007. Emotional context processing is impaired in
      schizophrenia. Cogn. Neuropsychiatry 12, 259-280.). We used a novel experimental
      task, the Emotion Context Processing Task (ECPT) to examine the influences of
      emotional context (IAPS pictures) on the processing of subtle surprised faces in
      schizophrenia. One of the task conditions included a manipulation designed to
      determine whether enhancing attention to the context (by requiring a
      categorization judgment on the context pictures) would facilitate the influence
      of context on facial emotion processing in schizophrenia. In addition, we tested
      whether deficits on a non-social context processing would predict deficits in the
      influence of context on facial emotion processing in schizophrenia. We
      administered the Dot Probe Expectancy Task (a non-social context processing task)
      and the ECPT to individuals with schizophrenia (n=35) and healthy controls
      (n=32). Individuals with schizophrenia showed an intact influence of context
      information on facial emotion recognition. The manipulation designed to enhance
      attention to emotional context reduced the effect of context for both groups. In
      schizophrenia, better processing of non-social context was associated with a
      stronger influence of context on valence ratings of facial expressions in the
      negative context condition. These results suggest in schizophrenia, similar
      mechanisms may influence the processing of context for both social and non-social
      information.

PMID- 21719259
TI  - Preparation and in vitro properties of redox-responsive polymeric nanoparticles
      for paclitaxel delivery.
AB  - Rice-like polymeric nanoparticles (NPs) composed of a new redox-responsive
      polymer, poly(ethylene glycol)-b-poly(lactic acid) (MPEG-SS-PLA), were prepared
      to carry paclitaxel (PTX) for glutathione (GSH)-regulated drug delivery. The PTX
      loaded MPEG-SS-PLA NPs were fabricated using an optimized oil-in-water
      emulsion/solvent evaporation method. The size and morphology of the prepared NPs
      were characterized by scanning electron microscopy (SEM). The SEM results
      demonstrate that the NPs were dispersed as individual particles and were rice
      shaped. The PTX loading efficiency, in vitro release, and stability of the NPs
      were analyzed by high-performance liquid chromatography (HPLC). The HPLC results
      revealed that the NPs released almost 90% PTX within 96 h when GSH presented at
      intracellular concentrations, whereas only a very small PTX amount was released
      at plasma GSH levels. The in vitro cytotoxicities of the NPs against A549, MCF-7,
      and HeLa carcinoma cells were assessed using a standard methyl thiazolyl
      tetrazoliun (MTT) assay. The MTT assay results show that the NPs caused
      concentration- and time-dependent changes in cell viability. To investigate the
      cellular uptake of the PTX-loaded NPs, visual endocytosis assay was performed
      using the fluorescent dye coumarin-6 as a model drug. The endocytosis assay
      results reveal rapid penetration and intracellular accumulation of coumarin-6
      loaded NPs, as well as rapid coumarin-6 dispersion from the NPs. Overall, these
      findings establish that the NPs containing the synthesized redox-responsive
      polymer MPEG-SS-PLA can be used as potential carrier systems for antitumor drug
      delivery.

PMID- 21719260
TI  - [Idiopathic nephrotic syndrome in children: from corticosteroids to rituximab].

PMID- 21719261
TI  - [A rare etiology of recurrent hemarthrosis in children].

PMID- 21719262
TI  - Follow-up on thyroidal uptake after radioiodine therapy: how robust is the peri
      therapeutic dosimetry?
AB  - Radioiodine therapy (RIT) for benign thyroid diseases in Germany requires the
      patient to stay in a nuclear medicine therapy ward for at least 48 hours and the
      dose to the thyroid to be computed from activity measurements performed during
      that stay. A major part of the total dose will be delivered after the patient's
      discharge from the hospital and thus has to be predicted through extrapolation
      with the effective half-life measured peri-therapeutically. We performed repeated
      thyroid uptake measurements on patients up to five months post therapy to
      investigate post-therapeutic changes in their effective half-lives and examine
      the dosimetric consequences. 12 patients (4 m, 8 f; age 36 - 76 y; 4 Graves'
      disease, 4 toxic adenoma, 3 toxic goitre, 1 non-toxic goitre) underwent late
      uptake measurements (1 - 7 meas., 13 - 154 d post administration, median 54 d,
      performed with thyroid probe resp. whole body counter at lower activities). Doses
      calculated from late measurements were compared to those predicted at discharge;
      half-lives calculated from the late measurement closest to the median delay (54
      d) were compared to those determined at time of discharge. A cross-calibration
      between activity calibrator, thyroid probe, and whole body counter over an
      activity range from 52 MBq down to 45 Bq revealed linearity to within 6%, which
      was considered sufficient. In 9 out of 12 patients the achieved dose was within
      the range predicted at discharge. Averaged deviation between achieved and
      predicted dose was 3.1+/-2.2% (median 2.5%, range 0.7% - 7.2%). Averaged
      deviation between post- and peri-therapeutic half-lives was 5.1+/-3.9% (median
      3.5%, range 1.3% - 12.5%). For n=5 patients discharged after 3 days, averaged
      deviations were greater (dose 4.0%, half-life 5.6%) than for those patients (n=7)
      who stayed in the hospital for a minimum of 4 days (dose 2.5%, half-life 4.8%).
      Excretion of iodine from the thyroid remains practically unchanged for at least
      two months after RIT. The dosimetric procedure implemented in our institution
      warrants a robust prediction of the post-therapeutic half-life and thus the
      actual achieved dose.

PMID- 21719263
TI  - [External radiation exposure and effective half-life in Lu-177-Dota-Tate
      therapy].
AB  - The aim of the study was to estimate the external radiation exposure emitted by
      the patient to his surroundings after discharge. Being in compliance with legal
      requirements is especially important when doing multiple therapies. To estimate
      the effective half-life to be used quite realistically, the individual effective
      half-lives for 41 patients with 52 therapies were calculated. From the resulting
      histogram the maximum value was determined to be 100 h. Substituting the physical
      half-life by this maximum effective half-life results in dose estimates, which
      are lower but still conservative. In addition, the analysis of dose related
      parameters for patients who underwent multiple therapies demonstrates that the
      parameters estimated for the first therapy cannot be transferred to the
      subsequent ones.

PMID- 21719264
TI  - [Radioembolization with (90)Y-labeled microspheres: post-therapeutic therapy
      validation with Bremsstrahlung-SPECT].
AB  - During the last years angiographic Selective Internal Radiotherapy (SIRT) with
      (90)Y-labelled microspheres has become a common technique for the local-ablative
      treatment of cancer patients. SIRT is a palliative therapy concept for the
      treatment of liver malignancies. As a result of (90)Y-decay as beta(-)-emitter
      without a concomitant gamma radiation, Bremsstrahlung imaging is needed to
      validate the distribution achieved by radioembolisation. This article
      demonstrates the method of imaging through phantom measurement and shows the
      advantages of post-therapeutic tomography by means of a patient study. Approaches
      for further optimization of Bremsstrahlung imaging are discussed.

PMID- 21719265
TI  - Determination of individual organ masses for (90)Y-anti-CD66 radioimmunotherapy:
      influence on therapy planning.
AB  - Dosimetry is important in the development of radioactive pharmaceuticals,
      especially for optimizing radionuclide therapy with respect to risk-benefit
      analysis. To calculate the applied absorbed doses in the target and risk organs
      standard phantom masses are frequently used. However, deviations to the true
      organ mass can lead to suboptimal decisions in dose finding studies. To estimate
      the magnitude of deviations introduced when using standard phantom masses instead
      of individual organ masses, we investigated 10 patients treated with
      radioimmunotherapy using (90)Y labelled anti-CD66 antibody. The use of standard
      phantom masses instead of individually measured organ masses results in mean
      deviations for liver, spleen and kidneys of 2% (Min. -22%, Max. 34%), -3% (Min. 
      34, Max. 100%) und -8% (Min. -37, Max. 38%), respectively. For the administered
      therapeutic activity differences of -16% (Min. -45%, Max. 4%) were observed
      depending on the used organ mass. These results demonstrate that using standard
      phantom masses for dosimetry before radionuclide therapy is not adequate.

PMID- 21719266
TI  - Protective immunity against malaria by 'natural immunization': a question of
      dose, parasite diversity, or both?
AB  - Plasmodium undergoes an obligate liver phase before the onset of malaria, which
      is caused exclusively by cyclic propagation of the parasite inside erythrocytes.
      The diagnostically inaccessible and clinically silent pre-erythrocytic expansion
      phase is a promising target for inducing sterilizing immunity against
      reinfections. Recent studies in rodent and human malaria models called attention
      to the induction of potent protective immunity by administration of anti-malarial
      drugs during sporozoite exposure. Here, we review the concept of drug-mediated
      pathogen arrest as a natural immunization strategy. This previously unrecognized
      immunological benefit might also open new opportunities for population-wide
      presumptive drug administration as an adjunct malaria control tool.

PMID- 21719267
TI  - Mortality of those who attended drug services in Scotland 1996-2006: record
      linkage study.
AB  - BACKGROUND: We examine major causes of death amongst persons in contact with drug
      treatment services across Scotland during April 1996-March 2006, hereafter
      Scottish Drug Misuse Database (SDMD) cohort. METHODS: Drug-treatment records were
      linked to national registers of deaths and hepatitis C virus (HCV) diagnoses. For
      eras 1996/97-2000/01 and 2001/02-2005/06, we calculated cause-specific death
      rates and standardised mortality ratios (SMRs) using age-, sex- and calendar
      rates of the general Scottish population. Major causes of death were identified
      by high SMRs (>5 across eras) or rates (>50 per 100,000 person-years in either
      era), and their time-specific influences characterised by proportional hazards
      analyses. RESULTS: The SDMD cohort comprised 69,456 individuals, 350,315 person
      years and 2590 deaths. The overall SMR reduced from 6.4 (95% CI: 6.0-6.9) to 4.8
      (95% CI: 4.6-5.0) between eras. We identified five major causes of death: drug
      related (1383 deaths), homicide (118) and infectious diseases (90) with high
      SMRs; suicide (269) and digestive system disease (168) with high rates. HCV
      diagnosis marked individuals with at least double the risk of cause-specific
      mortality, including adjusted hazard ratio (HR) for no HCV diagnosis of 0.46 (95%
      CI: 0.41-0.53) for drug-related deaths (DRDs) and 0.15 (95% CI: 0.10-0.22) for
      death from digestive system disease. Increased DRD risk at older age (>34 years)
      appeared specific to HCV-diagnosed individuals (interaction: chi12=7.7, p=0.01).
      Alcohol misuse increased HRs: for DRD (1.76, 95% CI: 1.50-2.06), suicide (1.88,
      95% CI: 1.35-2.60), deaths from digestive system disease (3.19, 95% CI: 2.21
      4.60) and non-major causes (1.87, 95% CI: 1.49-2.35). Stimulant misuse increased
      suicide risk: adjusted HR 1.91 (95% CI: 1.43-2.54). CONCLUSIONS: Drug-users in
      Scotland are exposed to variously increased mortality risks. HCV-diagnosed
      individuals are particularly vulnerable, and may need additional support.

PMID- 21719268
TI  - Gold nanoparticles-coated magnetic microspheres as affinity matrix for detection
      of hemoglobin A1c in blood by microfluidic immunoassay.
AB  - A novel microfluidic immunoassay system for specific detection of hemoglobin A1c
      (HbA1c) was developed based on a three-component shell/shell/core structured
      magnetic nanocomposite Au/chitosan/Fe(3)O(4), which was synthesized with easy
      handling feature of Fe(3)O(4) by magnet, high affinity for gold nanoparticles of
      chitosan and good immobilization ability for anti-human hemoglobin-A1c antibody
      (HbA1c mAb) of assembled colloidal gold nanoparticles. The resulting HbA1c
      mAb/Au/chitosan/Fe(3)O(4) magnetic nanoparticles were then introduced into
      microfluidic devices coupled with a gold nanoband microelectrode as
      electrochemical detector. After that, three-step rapid immunoreactions were
      carried out in the sequence of HbA1c, anti-human hemoglobin antibodies (Hb mAb)
      and the secondary alkaline phosphatase (AP)-conjugated antibody within 20 min.
      The current response of 1-naphtol obtained from the reaction between the
      secondary AP-conjugated antibody and 1-naphthyl phosphate (1-NP) increased
      proportionally to the HbA1c concentration. Under optimized electrophoresis and
      detection conditions, HbA1c responded linearly in the concentration of 0.05-1.5
      MUg mL(-1), with the detection limit of 0.025 MUg mL(-1). This system was
      successfully employed for detection of HbA1c in blood with good accuracy and
      renewable ability. The proposed method proved its potential use in clinical
      immunoassay of HbA1c.

PMID- 21719269
TI  - A rational approach in probe design for nucleic acid-based biosensing.
AB  - Development of nucleic acid-based sensing attracts the interest of many
      researchers in the field of both basic and applied research in chemistry. Major
      factors for the fabrication of a successful nucleic acid sensor include the
      design of probes for target sequence hybridization and their immobilization on
      the chip surface. Here we demonstrate that a rational choice of bioprobes has
      important impact on the sensor's analytical performances. Computational
      evaluations, by a simple and freely available program, successfully led to the
      design of the best probes for a given target, with direct application to nucleic
      acid-based sensing. We developed here an optimized and reproducible strategy for
      in silico probe design supported by optical transduction experiments. In
      particular Surface Plasmon Resonance imaging (SPRi), at the forefront of optical
      sensing, was used here as proof of principle. Five probes were selected,
      immobilized on gold chip surfaces by widely consolidated thiol chemistry and
      tested to validate the computational model. Using SPRi as the transducting
      component, real-time and label free analysis was performed, taking the Homo
      sapiens actin beta (ACTB) gene fragment as model system in nucleic acid
      detection. The experimental sensor behavior was further studied by evaluating the
      strength of the secondary structure of probes using melting experiments.
      Dedicated software was also used to evaluate probes' folding, to support our
      criteria. The SPRi experimental results fully validate the computational
      evaluations, revealing this approach highly promising as a useful tool to design
      biosensor probes with optimized performances.

PMID- 21719270
TI  - Fluorescent aptasensors based on conformational adaptability of abasic site
      containing aptamers in combination with abasic site-binding ligands.
AB  - Aptamers are nucleic acids that can selectively bind to a variety of targets.
      Aptamers usually undergo conformational transitions from a flexible or disordered
      structure into a rigid or ordered structure upon target-binding. This study
      describes a detection method for l-argininamide (l-Arm) and adenosine based on
      the conformational adaptability of nucleic acid aptamers. An abasic site (AP
      site) was formed in the stem and close to the target-binding site of a stem-loop
      aptamer as an anchoring pocket for a fluorescent ligand. 3,5-Diamino-6-chloro-2
      pyrazine carbonitrile (DCPC), which can bind to AP site-containing DNA duplexes
      by pseudo-base pairing, was utilized as a signaling reporter for the target
      binding. The binding of a target to an aptamer induces the tight pairing of bases
      flanking the AP site, so that DCPC can effectively bind to the stem. The binding
      of DCPC is accompanied by a significant enhancement of its fluorescence. This new
      sensing method without an antisense DNA strand was demonstrated by using l-Arm
      and its aptamer as a model. It was confirmed that the method can sensitively
      detect l-Arm with a detection limit of 2.1 MUM. The proposed method was also
      applied to adenosine detection, where the reported sequence of an adenosine
      aptamer was slightly modified. The method based on an AP site-containing aptamer
      and an AP site-binding ligand was applicable to detection of a target in horse
      serum.

PMID- 21719271
TI  - Carbon nanoparticle for highly sensitive and selective fluorescent detection of
      mercury(II) ion in aqueous solution.
AB  - In this article, carbon nanoparticles (CNPs) were used as a novel fluorescent
      sensing platform for highly sensitive and selective Hg(2+) detection. To the best
      of our knowledge, this is the first example of CNPs obtained from candle soot
      used in this type of sensor. The general concept used in this approach is based
      on that adsorption of the fluorescently labeled single-stranded DNA (ssDNA) probe
      by CNP via pi-pi stacking interactions between DNA bases and CNP leads to
      substantial dye fluorescence quenching; however, in the presence of Hg(2+), T
      Hg(2+)-T induced hairpin structure does not adsorb on CNP and thus retains the
      dye fluorescence. A detection limit as low as 10nM was achieved. The present CNP
      based biosensor for Hg(2+) detection exhibits remarkable specificity against
      other possible metal ions. Furthermore, superior selectivity performance was
      observed when Hg(2+) detection was carried out in the presence of a large amount
      of other interference ions. Finally, in order to evaluate its potential practical
      application, Hg(2+) detection was conducted with the use of lake water other than
      pure buffer and it is believed that it holds great promise for real sample
      analysis upon further development.

PMID- 21719272
TI  - Aqueous fullerene aggregates (nC60) generate minimal reactive oxygen species and
      are of low toxicity in fish: a revision of previous reports.
AB  - This review aims to clarify inconsistencies in previous reports regarding the
      potential for aqueous aggregates of fullerenes (nC60) to generate reactive oxygen
      species (ROS) and cause toxicity in fish. Methods for evaluation of ROS
      production and toxicity of aqueous nC60 have evolved over time and limitations in
      initial studies have led to unintentional erroneous reports of nC60 ROS
      generation and toxicity. Some of these reports continue to lead to misconceptions
      of the environmental effects of C60. Critical review of the evidence (2007-2011)
      indicates that aqueous nC60 have minimal potential to produce ROS and that
      oxidative stress in fish is not induced by environmentally relevant exposure to
      nC60. Future studies should acknowledge that current evidence indicates low
      toxicity of nC60 and refrain from citing articles that attribute toxicity in fish
      to nC60 based on methods shown to be compromised by experimental artifacts.
      Despite low toxicity of nC60 in fish, an emerging environmental issue is that
      nC60 can affect environmental fate, transport, and bioavailability of co
      contaminants in aquatic environments in a similar manner to that observed for
      other anthropogenic particulates (e.g., microplastics).

PMID- 21719273
TI  - Dosimetric evaluation of two treatment planning systems for high dose rate
      brachytherapy applications.
AB  - Various treatment planning systems are used to design plans for the treatment of
      cervical cancer using high-dose-rate brachytherapy. The purpose of this study was
      to make a dosimetric comparison of the 2 treatment planning systems from Varian
      medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192
      source generated with a single dwell position was compared using ABACUS (version
      3.1) and BrachyVision (version 6.5) planning systems. Ten patients with
      intracavitary applications were planned on both systems using orthogonal
      radiographs. Doses were calculated at the prescription points (point A, right and
      left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell
      position, little difference was observed in the doses to points along the
      perpendicular bisector. The mean difference between ABACUS and BrachyVision for
      these points was 1.88%. The mean difference in the dose calculated toward the
      distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the
      proximal end the difference was 19.82%. For the patient case there was
      approximately 2% difference between ABACUS and BrachyVision planning for dose to
      the prescription points. The dose difference for the reference points ranged from
      0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%,
      respectively. The dose difference between the rectum points was statistically
      significant. There is considerable difference between the dose calculations
      performed by the 2 treatment planning systems. It is seen that these
      discrepancies are caused by the differences in the calculation methodology
      adopted by the 2 systems.

PMID- 21719275
TI  - Two-stage fungal biopulping for improved enzymatic hydrolysis of wood.
AB  - A novel two-stage, whole organism fungal biopulping method was examined for
      increasing the yield of enzymatic hydrolysis of wood into soluble glucose.
      Liriodendron tulipifera wood chips (1g) were exposed to liquid culture
      suspensions of white rot (Ceriporiopsis subvermispora) or brown rot (Postia
      placenta) fungi and incubated at 28 degrees C, either alone in single-stage 30
      day (one fungal species applied) or two-stage 60 day (both fungal species applied
      in alternative succession) treatments. Fungi grew in all treatments, but did not
      significantly decrease the percent carbohydrate content of the wood. Two-stage
      treatments differed significantly in mass loss depending on order of exposure,
      suggesting additive or inhibitory fungal interactions occurred. Treatments
      consisting of C. subvermispora followed by P. placenta exhibited 6 +/- 0.5% mass
      loss and increased the yield of enzymatic hydrolysis by 67-119%. This significant
      hydrolysis improvement suggests that fungal biopulping technologies could support
      commercial lignocellulosic ethanol production efforts if further developed.

PMID- 21719274
TI  - The structural biology of beta-barrel membrane proteins: a summary of recent
      reports.
AB  - The outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts all
      contain transmembrane beta-barrel proteins. These beta-barrel proteins serve
      essential functions in cargo transport and signaling and are also vital for
      membrane biogenesis. They have also been adapted to perform a diverse set of
      important cellular functions including acting as porins, transporters, enzymes,
      virulence factors and receptors. Recent structures of transmembrane beta-barrels
      include that of a full length autotransporter (EstA), a bacterial heme
      transporter complex (HasR), a bacterial porin in complex with several ligands
      (PorB), and the mitochondrial voltage-dependent anion channel (VDAC) from both
      mouse and human. These represent only a few of the interesting structures of beta
      barrel membrane proteins recently elucidated. However, they demonstrate many of
      the advancements made within the field of transmembrane protein structure in the
      past few years.

PMID- 21719276
TI  - Isolation of natural cultures of anaerobic fungi and indigenously associated
      methanogens from herbivores and their bioconversion of lignocellulosic materials
      to methane.
AB  - This study aimed to obtain natural cultures of anaerobic fungi and their
      indigenously associated methanogens from herbivores and investigate their ability
      to degrade lignocelluloses to methane. Eight natural cultures were obtained by
      Hungate roll tube technique. The fungi were identified as belonging to Piromyces,
      Anaeromyces and Neocallimastix respectively by microscopy, and the methanogens as
      Methanobrevibacter spp. by 16S rRNA gene sequencing. In vitro studies with rice
      straw showed that these cultures degraded 33.5-48.3% substrate and produced 0.33
      0.84 mmol/(100ml culture) methane. Two cultures were further selected for their
      ability to degrade different lignocellulosic materials and could produce 0.38
      1.27 mmol/(100ml culture) methane. When methanogens were inhibited, the
      lignocellulose-degrading ability of cultures significantly reduced. In
      conclusion, natural cultures of anaerobic fungi with indigenously associated
      methanogens with high fiber degradation ability were obtained, and these cultures
      may have the potential in industrial use in lignocelluloses degradation and
      methane production.

PMID- 21719277
TI  - Sludge drying reed beds for septage treatment: towards design and operation
      recommendations.
AB  - This paper focuses on the feasibility of septage treatment by sludge drying reed
      beds (SDRB). Different designs and operation conditions of SRDB pilot-scales were
      tested on system efficiencies such as the top filtration layer (sand or compost)
      and the organic load (30 and 50 kg SSm(-2)y(-1)). Results focus on the obtained
      performances considering sludge characteristics, filtration efficiencies,
      percolate qualities, and sludge deposit properties. Although results show better
      filtration efficiency for activated sludge (e.g. SS removal around 98.4%) than
      for septage (e.g. SS removal around 87.5%), the feasibility of septage treatment
      with SDRB has been demonstrated with, at 50 kg SSm(-2)y(-1) sludge accumulation,
      and dry matter about 7.9 cm y(-1) and 70% (summer period), respectively. Further
      design and operation condition recommendations for SDRB treating septage are
      proposed.

PMID- 21719278
TI  - The feasibility of using a two-stage autotrophic nitrogen removal process to
      treat sewage.
AB  - The feasibility of using a two-stage autotrophic nitrogen removal process to
      treat sewage was examined in this study. The obtained results showed that total
      nitrogen (TN) could be efficiently removed by 88.38% when influent TN and
      chemical oxygen demand (COD) were 45.87 and 44.40 mg/L, respectively. In the
      first stage, nitritation was instantly achieved by the bioaugmentation strategy,
      and can be maintained under limited oxygen condition (below 0.2mg/L). The ratio
      of nitrite to ammonium in the effluent of the nitritation reactor can be
      controlled at approximate 1.0 by adjusting aeration rate. In the second stage,
      anammox was realized in the upflow anaerobic sludge blanket (UASB) reactor, where
      the total nitrogen removal rate was 0.40 kg Nm(-3)d(-1) under limited-substrate
      condition. Therefore, the organic matter in sewage can be firstly concentrated in
      biomass which could generate biogas (energy). Then, nitrogen in sewage could be
      removed in a two-stage autotrophic nitrogen removal process.

PMID- 21719279
TI  - Engineering ethanologenic Escherichia coli for levoglucosan utilization.
AB  - Levoglucosan is a major product of biomass pyrolysis. While this pyrolyzed
      biomass, also known as bio-oil, contains sugars that are an attractive
      fermentation substrate, commonly-used biocatalysts, such as Escherichia coli,
      lack the ability to metabolize this anhydrosugar. It has previously been shown
      that recombinant expression of the levoglucosan kinase enzyme enables use of
      levoglucosan as carbon and energy source. Here, ethanologenic E. coli KO11 was
      engineered for levoglucosan utilization by recombinant expression of levoglucosan
      kinase from Lipomyces starkeyi. Our engineering strategy uses a codon-optimized
      gene that has been chromosomally integrated within the pyruvate to ethanol (PET)
      operon and does not require additional antibiotics or inducers. Not only does
      this engineered strain use levoglucosan as sole carbon source, but it also
      ferments levoglucosan to ethanol. This work demonstrates that existing
      biocatalysts can be easily modified for levoglucosan utilization.

PMID- 21719280
TI  - Evolution of clostridia and streptomycetes in full-scale composting facilities
      and pilot drums equipped with on-line temperature monitoring and aeration.
AB  - The evolution of sporulating bacteria in full-scale composting facilities with
      online temperature monitoring has been poorly studied, although organic matter
      recycling increases. We analysed Clostridium perfringens and sulphite-reducing
      clostridia (SRC) by cultivation, and streptomycetes by real-time PCR in five full
      scale, temperature-monitored and aerated composting processes, and two pilot
      scale drum composters. Facilities composted woodchips, sawdust, peat, or bark
      amended sludge or source-separated biowaste. Streptomycetes genes of 0.21
      110*10(7)copies/g feed increased fast to 0.019-33*10(9)copies/g, and then were
      equal or decreased. SRC of 0.06-2.2*10(7)cfu/g feed decreased to 0-600 cfu/g,
      with re-growth in two facilities. End products were clean of C. perfringens,
      detected in sludge composts. Although processes contained large quantities of
      spore-forming bacteria, in the best facilities end products had the high quality.
      Temperature (>55 degrees C,>2d) was not related to the end compost quality, but
      relations between waste and bulking agent qualities, aeration, and processing
      time should be better controlled.

PMID- 21719281
TI  - Integration of on-farm biodiesel production with anaerobic digestion to maximise
      energy yield and greenhouse gas savings from process and farm residues.
AB  - Anaerobic co-digestion of residues from the cold pressing and trans
      esterification of oilseed rape (OSR) with other farm wastes was considered as a
      means of enhancing the sustainability of on-farm biodiesel production. The study
      verified the process energy yields using biochemical methane potential (BMP)
      tests and semi-continuous digestion trials. The results indicated that high
      proportions of OSR cake in the feedstock led to a decrease in volatile solids
      destruction and instability of the digestion process. Co-digestion with cattle
      slurry or with vegetable waste led to acceptable specific and volumetric methane
      productions, and a digestate low in potentially toxic elements (PTE). The results
      were used to evaluate energy balances and greenhouse gas emissions of the
      integrated process compared with biodiesel production alone. Co-digestion was
      shown to provide energy self-sufficiency and security of supply to farms, with
      sufficient surplus for export as fuel and electricity.

PMID- 21719282
TI  - Discovery of bacterial NAD+-dependent DNA ligase inhibitors: optimization of
      antibacterial activity.
AB  - Optimization of adenosine analog inhibitors of bacterial NAD(+)-dependent DNA
      ligase is discussed. Antibacterial activity against Streptococcus pneumoniae and
      Staphylococcus aureus was improved by modification of the 2-position substituent
      on the adenine ring and 3'- and 5'-substituents on the ribose. Compounds with
      logD values 1.5-2.5 maximized potency and maintained drug-like physical
      properties.

PMID- 21719283
TI  - Benzisothiazolones as modulators of macrophage migration inhibitory factor.
AB  - Substituted N-phenylbenzisothiazolones have been investigated as inhibitors of
      the tautomerase activity of the proinflammatory cytokine MIF (macrophage
      migration inhibitory factor). Numerous compounds were found to possess antagonist
      activity in the low micromolar range with the most potent being the 6-hydroxy
      analog 1w. Compound 1w and the p-cyano analog 1c were also shown to exhibit
      significant inhibition of the binding of MIF to its transmembrane receptor CD74.
      Consistently, both compounds were also found to retard the MIF-dependent
      phosphorylation of ERK1/2 in human synovial fibroblasts.

PMID- 21719284
TI  - Facile conversion of RNA aptamers to modular fluorescent sensors with tunable
      detection wavelengths.
AB  - A GTP aptamer was converted to a modular fluorescent GTP sensor by conjugation of
      RRE (Rev responsive element) RNA and successive complex formation with a
      fluorophore-modified Rev peptide. Structural changes associated with substrate
      binding in the RNA aptamer were successfully transduced into changes in
      fluorescence intensity because of the modular structure of ribonucleopeptides. A
      simple modular strategy involving conjugation of a fluorophore-modified
      ribonucleopeptide to the stem region of an RNA aptamer deduced from secondary
      structural information helps produce fluorescent sensors, which allow tuning of
      excitation and detection wavelengths through the replacement of the fluorophore
      at the N-terminal of the Rev peptide.

PMID- 21719285
TI  - Antiproliferative activity of dmoPTA-Ru(II) complexes against human solid tumor
      cells.
AB  - The biological evaluation of new Ru(II) complexes carrying dmoPTA (dmoPTA=3,7
      dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) ligands is reported. The
      results on the biological activity revealed that the organometallic complexes are
      active against all cell lines with GI(50) values in the range 1.1-2.6 MUM. When
      compared to the standard anticancer drug cisplatin, the bimetallic Ru(II)
      complexes showed a greater activity profile. The cell cycle analysis revealed
      that the new compounds induced arrest in G(1) phase. Contrary to cisplatin, these
      Ru(II) complexes do not interact with DNA. This result suggests that DNA might
      not be the key pharmacological target.

PMID- 21719286
TI  - Identification of benzofuran-4,5-diones as novel and selective non-hydroxamic
      acid, non-peptidomimetic based inhibitors of human peptide deformylase.
AB  - Selective inhibitors of human peptide deformylase (HsPDF) are predicted to
      constitute a new class of antitumor agents. We report the identification of
      benzofuran-4,5-diones as the first known selective HsPDF inhibitors and we
      describe their selectivity profile in a panel of metalloproteases. We
      characterize their structure-activity relationships for antitumor activity in a
      panel of cancer cell lines, and we assess their in vivo efficacy in a mouse
      xenograft model. Our results demonstrate that selective HsPDF inhibitors based on
      the benzofuran-4,5-dione scaffold constitute a novel class of antitumor agents
      that are potent in vitro and in vivo.

PMID- 21719287
TI  - Osteogenic constituents from Pterospermum acerifolium Willd. flowers.
AB  - Phytochemical investigation of ethanol extracts of the Pterospermum acerifolium
      flowers led to the isolation and identification of two new flavones, 4'-(2
      methoxy-4-(1,2,3-trihydroxypropyl) phenoxy luteolin (1) and 5,7,3'-trihydroxy-6-O
      beta-D-glucopyranosyl flavone (2), and one new lactone, 3,5-dihydroxyfuran-2(5H)
      one (3) along with 14 known compounds (4-17). The structure of compounds 1-17 was
      established based on MS, 1D and 2D NMR, spectroscopic analysis. Eight of these
      compounds (1-6, 8 and 9) were assessed for osteogenic activity by using primary
      cultures of rat osteoblast. The compounds 1, 3 and 4 significantly stimulated
      osteoblast differentiation and mineralization as evident from a marked increase
      in expression of alkaline phosphatase and alizarin red-S staining of osteoblasts.

PMID- 21719288
TI  - A clinicopathological and neuroradiological study of paediatric meningioma from a
      single centre.
AB  - Paediatric meningiomas are rare intracranial neoplasms representing 0.4% to 4.1%
      of tumours in paediatric patients and 1.5% to 1.8% of all intracranial
      meningiomas. The goal of this study was to determine the epidemiology, clinical
      presentation, radiological features, morphological spectrum and treatment outcome
      of paediatric meningiomas. All evaluable reports of meningioma in children from 1
      January 1999 to 31 December 2009 were retrieved from the database of our
      Department of Pathology and were assessed retrospectively. This study describes
      12 patients (nine males, three females; age range, 4-18 years; mean, 12.8 years).
      Their age and sex distribution, presenting symptoms, neurological findings,
      location, neuroradiological and histopathological findings were reviewed and the
      results were compared with published reports. Atypical and malignant meningiomas
      seem to be more common in childhood and adolescence than in adulthood.

PMID- 21719289
TI  - Microsurgical treatment of intracranial chondroma.
AB  - Intracranial chondromas are rare benign tumors. Little data are available on the
      diagnosis and treatment of these tumors. Thus, we aimed to describe a large
      series of patients with intracranial chondroma and to analyze and discuss the
      clinical features and microsurgical treatment of these patients. We
      retrospectively analyzed the clinical data of 30 patients (12 males and 18
      females; mean age 35.4 years; age range 16-60 years) who had pathologically
      confirmed intracranial chondroma treated at our hospital from September 1996 to
      June 2008. Surgery was performed on all 30 patients: five patients underwent
      postoperative radiotherapy; 26 patients were followed up postoperatively for a
      mean duration of 45.8 months. The surgical approach was selected according to
      tumor location. Total resection was achieved in 11 patients, subtotal resection
      in 13, and partial resection in nine (three patients had recurrent chondroma).
      Follow-up showed that 21 patients recovered without recurrences, three had
      recurrence, and two patients died. The clinical manifestations included headache
      and multiple cranial nerve lesions. Imaging usually showed a well-demarcated
      extramedullary tumor, centrally located, without surrounding brain edema,
      partially calcified (73.3%) and with minimal vascularity, often accompanied by
      erosion and destruction of surrounding bone (56.7%). It is difficult to totally
      remove an intracranial chondroma, and it is not possible to differentiate a
      chondroma from a myxoma or chordoma at the cranial base on the basis of clinical
      manifestations and neuroradiological findings. Selection of the appropriate
      surgical approach is important for resection of the tumor.

PMID- 21719290
TI  - Flow diverting stents for cerebral aneurysm treatment: time to replace coiling?

PMID- 21719291
TI  - Physical and functional cooperation of neural cell adhesion molecule and beta1
      integrin in neurite outgrowth induction.
AB  - Neural cell adhesion molecule (NCAM) and beta1-integrin are both involved in cell
      differentiation, with changes in the expression of these two molecules
      correlating with changes in the malignancy of tumor cells. There is a known
      functional correlation between NCAM and beta1-integrin in adhesion and also
      neurite outgrowth in tumor cells. In the present study, we used immunostaining
      and immunoprecipitation studies to demonstrate that isoform 120 of NCAM
      associates physically as well as functionally with beta1-integrin in the
      induction of neurite outgrowth in SH-SY5Y-human neuroblastoma cells. The
      interaction between these two molecules is mandatory for neurite outgrowth. NCAM
      blockage completely inhibits the effects of beta1-integrin on neurite outgrowth.
      These findings further our understanding of the interactions between NCAMs and
      integrins in malignancy.

PMID- 21719292
TI  - Neuromelanin magnetic resonance imaging of nigral volume loss in patients with
      Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by progressive degeneration of melanin
      containing neurons in the substantia nigra pars compacta (SNc). Pathological
      change has not been detected by neuroimaging techniques in patients with PD in
      vivo. We examined 80 patients with PD to determine whether degeneration of the
      SNc is detectable in vivo by MRI. The age-matched controls consisted of 54
      patients who had suffered mild acute ischemic stroke. Axial T1-weighted MRI were
      obtained with a 3-Tesla MRI scanner. The border of the neuromelanin-sensitive
      region in the SNc was traced manually on these images, and the volume of this
      area was calculated. The mean volumes for the left and right SNc were
      significantly reduced in patients with PD compared to the controls. Volume loss
      became marked in parallel with disease severity and duration. Neuromelanin MRI
      may be considered as a biomarker of nigral degeneration in patients with PD.

PMID- 21719293
TI  - Recommendations for patient selection in spinal cord stimulation.
AB  - Studies have shown that spinal cord stimulation (SCS) can reduce chronic pain by
      at least 50% over prolonged periods, improve function and quality-of-life, reduce
      requirements for healthcare resources and enable return to work in appropriately
      selected patients. However, SCS does not provide pain relief in all patients and
      is an expensive, labor intensive and invasive procedure with complications and
      ongoing management that requires specialists with specific skills and judgment.
      Multidisciplinary selection of appropriate patients for SCS is essential to
      achieve maximal benefit from the procedure. The aim of the article is to provide
      a clinical practice guide to the likely effectiveness of SCS in treating various
      types of chronic pain, as supported by the literature. The article will summarize
      indications and contraindications for SCS, provide guidance on the selection and
      timing for referral, and highlight the benefits and complications associated with
      the procedure.

PMID- 21719294
TI  - Intraoperative MRI with integrated functional neuronavigation-guided resection of
      supratentorial cavernous malformations in eloquent brain areas.
AB  - Between March 2009 and January 2010, 36 patients with 38 supratentorial cavernous
      malformations in eloquent brain areas underwent surgery with the aid of
      intraoperative MRI (iMRI), functional neuronavigation, and electrocorticography
      (ECoG). To optimize outcomes, the hemosiderin-stained tissue surrounding the
      lesion in addition to the cavernous malformation itself (lesion) was
      microsurgically removed, leaving behind only small areas adjacent to, or
      overlapping with, functional areas. According to the Zabramski classification,
      there were 13 type I lesions, which all underwent total resection. There were 25
      type II or III lesions with a surrounding hypointense rim, and all of these
      lesions were completely removed; the surrounding hypointense rims were completely
      removed in 15 patients and partially removed in 10. No new neurologic disorders
      occurred postoperatively. Twenty patients had preoperative epileptic seizures,
      nine of whom were refractory to treatment. During follow-up, seizure outcome was
      assessed using the Engel classification, and 11 patients with non-refractory
      epilepsy had a class I outcome. Of the nine patients with refractory epilepsy,
      seven (77.8%) had a class I outcome, one (11.1%) had a class II outcome, and one
      (11.1%) had a class III outcome.

PMID- 21719295
TI  - Pioneering concepts in epileptology: the cerebral dysrhythmia of Frederic Gibbs
      (1903-92) and William Lennox (1884-1960).
AB  - The development of the electroencephalogram and its use in the study of epilepsy
      supplied the research team of William Lennox and Frederic (Frederick) Gibbs at
      Harvard University with an entirely new method of studying the epileptic activity
      of the brain. The abnormal activity, thought to be a "dysrhythmia", seemed to
      indicate a central role for inheritance in this condition, and there seemed a
      more considerable penetration of inheritable epileptic tendency in the community
      than at first thought. Lennox, who had a long-held interest in eugenics, felt
      that further study was needed and this he undertook in his famous "Twin Series"
      exploring epilepsy in identical and non-identical twin pairs. Frederic and Erna
      Gibbs, however, went on to study the electrical activity accompanying various
      clinical seizure types. These were the early days of electroencephalography, and
      mistaken over-emphasis given to various forms of non-specific slower components
      introduced conceptual errors in both areas of research. However, the overall
      results of this pioneering research provided very significant advances in
      epileptology.

PMID- 21719296
TI  - Evaluation of potentially modifiable physical factors as predictors of health
      status in knee osteoarthritis patients referred for physical therapy.
AB  - The purpose of this cross sectional study was to estimate the contributions of
      potentially modifiable physical factors to variations in perceived health status
      in knee osteoarthritis (OA) patients referred for physical therapy. Health status
      was measured by three questionnaires: Knee injury and Osteoarthritis Outcome
      Score (KOOS); Knee Outcome Survey - Activities of Daily Living Scale (KOS-ADLS);
      and Medical Outcomes Study - 36 item Short Form (SF-36). Physical factors were
      measured by a battery of tests: body mass index (BMI); visual analog scale (VAS)
      of pain intensity; isometric dynamometry; universal goniometry; step test (ST);
      timed "up and go" test (TUGT); 20-meter walk test (20MWT); and 6-minute walk test
      (6MWT). All tests were administered to 136 subjects with symptomatic knee OA (94
      females, 42 males; age: 67.2 +/- 7.1 years). Multiple stepwise regression
      analyses revealed that knee muscle strength, VAS of pain intensity, 6MWT, degree
      of knee flexion and BMI were moderate predictors of health status. In the final
      models, selected combinations of these potentially modifiable physical factors
      explained 22% to 37% of the variance in KOOS subscale scores, 40% of the variance
      in the KOS-ADLS scale score, and 21% to 34% of the variance in physical health SF
      36 subscale scores. More research is required in order to evaluate whether
      therapeutic interventions targeting these potentially modifiable physical factors
      would improve health status in knee OA patients.

PMID- 21719297
TI  - Synthesis and SERCA activities of structurally simplified cyclopiazonic acid
      analogues.
AB  - The indole alkaloid cyclopiazonic acid (CPA) is one of the few known nanomolar
      inhibitors of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) besides the
      anticancer drug thapsigargin and the antiplasmoidal terpenoid artemisinin. Due to
      its less complex structure CPA represents an attractive lead structure for the
      development of novel antimalarial drugs or for applications in the field of plant
      protection. We report here the first syntheses of structurally simplified CPA
      fragments and discuss their SERCA activities on the basis of published crystal
      structures of CPA-SERCA complexes.

PMID- 21719298
TI  - Design, syntheses, and kinetic evaluation of 3-(phenylamino)oxazolidine-2,4
      diones as potent cytochrome bc1 complex inhibitors.
AB  - The cytochrome bc1 complex (EC 1.10.2.2, bc1) is one of the most promising
      targets for new drugs and agricultural fungicides. Among the existing bc1 complex
      inhibitors specifically binding to the Q(o) site, oxazolidinedione derivatives
      have attracted great attention. With the aim to understand the substituent
      effects of oxazolidinedione derivatives on the inhibition activity against the
      bc1 complex, a series of new oxazolidinedione derivatives were designed,
      synthesized, and biologically evaluated. The further inhibitory kinetics studies
      against porcine succinate-cytochrome c reductase (SCR) revealed that the
      representative compound 8d and famoxadone are both non-competitive inhibitors
      with respect to the substrate cytochrome c, but competitive inhibitors with
      respect to substrate decylubiquinol (DBH2). In addition, compound 8d and
      famoxadone showed, respectively, 35-fold and 15-fold greater inhibitory activity
      against the porcine SCR than the porcine bc1 complex, indicating that these two
      inhibitors not only inhibited the activity of the bc1 complex, but possibly
      affect the interaction between the complex II and the bc1 complex. To our
      knowledge, this is the first report that famoxadone and its analogs have effects
      on the interaction between the complex II and the bc1 complex.

PMID- 21719299
TI  - Synthesis and biological activity of naphthyl-substituted (B-ring) benzophenone
      derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
AB  - A novel series of benzophenone derivatives with B-ring substituted by naphthyl
      ring has been synthesized and evaluated as non-nucleoside HIV-1 reverse
      transcriptase inhibitors. Most of these compounds showed good to moderate
      activity against wild-type HIV-1 and mutated viruses. In particular, the analogue
      10i demonstrated the most potent activity against wild-type HIV-1 with an EC50
      value of 4.8 nM, and with a high selectivity index up to 10347.9, it also proved
      to be active against the HIV-1 double mutant strain A17 (K103N+Y181C) with an
      EC50 value of 2.1 MUM. In addition, the molecular modeling study was used to
      explore the major interactions between the potent inhibitors with the HIV-1 RT.
      The investigation of the structure-activity relationships may serve as an
      important lead for the further optimization.

PMID- 21719300
TI  - Synthesis and antiviral evaluation of 9-(S)-[3-alkoxy-2
      (phosphonomethoxy)propyl]nucleoside alkoxyalkyl esters: inhibitors of hepatitis C
      virus and HIV-1 replication.
AB  - We reported previously that octadecyloxyethyl 9-(S)-[3-hydroxy-2
      (phosphonomethoxy)-propyl]adenine (ODE-(S)-HPMPA) was active against genotype 1b
      and 2a hepatitis C virus (HCV) replicons. This is surprising because acyclic
      nucleoside phosphonates have been regarded as having antiviral activity only
      against double stranded DNA viruses, HIV and HBV. We synthesized
      octadecyloxyethyl 9-(S)-[3-methoxy-2-(phosphonomethoxy)propyl]-adenine and found
      it to be active in genotype 1b and 2a HCV replicons with EC50 values of 1-2 MUM
      and a CC50 of > 150 MUM. Analogs with substitutions at the 3'-hydroxyl larger
      than methyl or ethyl, or with other purine bases were less active but most
      compounds had significant antiviral activity against HIV-1 in vitro. The most
      active anti-HIV compound was octadecyloxyethyl 9-(R)-[3-methoxy-2
      (phosphonomethoxy)propyl]guanine with an EC50 < 0.01 nanomolar and a selectivity
      index of > 4.4 million.

PMID- 21719301
TI  - Understanding non-enzymatic aminophospholipid glycation and its inhibition. Polar
      head features affect the kinetics of Schiff base formation.
AB  - Non-enzymatic aminophospholipid glycation is an especially important process
      because it alters the stability of lipid bilayers and interferes with cell
      function and integrity as a result. However, the kinetic mechanism behind this
      process has scarcely been studied. As in protein glycation, the process has been
      suggested to involve the formation of a Schiff base as the initial, rate
      determining step. In this work, we conducted a comparative kinetic study of
      Schiff base formation under physiological conditions in three low-molecular
      weight analogues of polar heads in the naturally occurring aminophospholipids O
      phosphorylethanolamine (PEA), O-phospho-DL-serine (PSer) and 2
      aminoethylphenethylphosphate (APP) with various glycating carbonyl compounds
      (glucose, arabinose and acetol) and the lipid glycation inhibitor pyridoxal 5'
      phosphate (PLP). Based on the results, the presence of a phosphate group and a
      carboxyl group in alpha position respect to the amino group decrease the
      formation constant for the Schiff base relative to amino acids. On the other
      hand, esterifying the phosphate group with a non-polar substituent in APP
      increases the stability of its Schiff base. The observed kinetic formation
      constants of aminophosphates with carbonyl groups were smaller than those for
      PLP. Our results constitute an important contribution to understanding the
      competitive inhibition effect of PLP on aminophospholipid glycation.

PMID- 21719302
TI  - Mandibular midline distraction: a systematic review.
AB  - INTRODUCTION: A systematic review of mandibular midline distraction (MMD) was
      carried out to assess effectiveness, treatment related difficulties,
      complications and biomechanical effects of this treatment modality objectively.
      MATERIAL & METHODS: Randomized controlled trials (RCT), controlled clinical
      trials (CCT) and case series concerning MMD with a sample size of >5 were
      searched electronically in Pubmed/Medline, Embase, Cochrane and CENTRAL up to
      September 6th 2010. RESULTS: 85 unique articles were found of which 22 met our
      inclusion criteria. The study designs of the articles found were prospective (9),
      retrospective (9) or uncertain (2). One clinical trial and no randomized clinical
      trials were found. The methodological quality was considered low in most
      articles. CONCLUSION: Generally MMD is a safe and effective treatment modality to
      treat transverse mandibular discrepancies, however controversies still exist:
      choice of distractor, surgical setting, distraction rate, start of orthodontic
      treatment and relapse. In addition, little is known about patient experience and
      quality of life after treatment. Further prospective trials are necessary to
      address these controversies and questions.

PMID- 21719303
TI  - Synthesis, spectroscopic and electrochemical studies of N,N-bis[(E)-2
      thienylmethylidene]-1,8-naphthalenediamine and its Cu(II) complex: DNA cleavage
      and generation of superoxide anion.
AB  - A novel tetradentate Cu(II) complex of the type, [CuL](NO(3))(2) was synthesized
      by the interaction of Schiff base ligand, N,N-bis[(E)-2-thienylmethylidene]-1,8
      naphthalenediamine, L obtained by the condensation of thiophene-2-carboxaldehyde
      and 1,8-diaminonaphthalene. The formation of Schiff base ligand, L and its Cu(II)
      complex was confirmed on the basis of results of elemental analyses, mass, FT-IR,
      (1)H and (13)C{(1)H} NMR spectral studies. UV-Vis, EPR and magnetic
      susceptibility data support a square planar environment around Cu(II) ion.
      However, molar conductance values confirmed 1:2 electrolytic nature for the
      Cu(II) complex. The electrochemical studies of Cu(II) complex was carried out by
      using cyclic voltammetry which revealed the complex to exhibit quasi reversible
      process. The biological activity of Cu(II) complex such as ability to bind DNA
      and DNA cleavage were studied where the Cu(II) complex was shown to cause
      considerable DNA cleavage and also generated reactive oxygen species such as
      superoxide anion. Since it is known that various anticancer drugs act through
      induction of oxidative stress that is mediated by reactive oxygen species, our
      results suggest a putative role of Cu(II) complex similar to various anticancer
      drugs.

PMID- 21719304
TI  - Primary plasma cell leukemia in the era of new drugs: has something changed?
AB  - Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple
      myeloma. This disease is associated with a very poor prognosis, and unfortunately
      it has not significantly improved during the last three decades. Autologous stem
      cell transplantation is generally recommended in eligible patients, but survival
      in transplanted PPCL patients is significantly lower than that of multiple
      myeloma. Recent preliminary data indicate that new drugs, in particular
      lenalidomide and bortezomib, could significantly improve the clinical outcome of
      PPCL, increasing response rate and duration, as well as survival. In this review
      we report an updated literature analysis about the current therapeutic scenario
      of PPCL, with a particular focus on the use of novel agents.

PMID- 21719306
TI  - Methods to select suitable fetal bovine serum for use in quality control assays
      for the detection of adventitious viruses from biological products.
AB  - Production of biological products, especially vaccines, usually requires
      materials derived from animals, and there are always risks that animal pathogens
      derived from these materials could contaminate the final products. Detection of
      adventitious agents is performed by quality control tests. In these biological
      assays, animal derived materials are also used and another problem arises, as
      fetal bovine serum (FBS) is used as an ingredient in tissue culture media. FBS
      contaminated with bovine viral diarrhea virus (BVDV) or other bovine pathogens,
      as well as antibodies against these pathogens may lead to false results in
      quality control assays. In this study, in order to determine the actual status of
      commercial FBS, we performed quality tests on various FBS samples. As a result,
      in 28 of 49 FBS samples (57.1%), pestivirus genes were detected by pan-pestivirus
      reverse transcription-polymerase chain reaction assay. Furthermore, two samples
      contained infectious BVDV. Neutralizing antibodies against BVDVs were detected in
      48 of 49 samples (97.6%) by the virus neutralization test based on the serum
      dilution or virus-dilution methods. Antibodies against other bovine pathogens
      were detected rarely in these samples. From our results, we recommend methods to
      select FBS that are focused on detection of BVDV and neutralizing antibodies
      against BVDV.

PMID- 21719305
TI  - MafA and MafB activity in pancreatic beta cells.
AB  - Analyses in mouse models have revealed crucial roles for MafA (musculoaponeurotic
      fibrosarcoma oncogene family A) and MafB in islet beta cells, with MafB being
      required during development and MafA in adults. These two closely related
      transcription factors regulate many genes essential for glucose sensing and
      insulin secretion in a cooperative and sequential manner. Significantly, the
      switch from MafB to MafA expression also appears to be vital for functional
      maturation of beta cells produced by human embryonic stem (hES) cell
      differentiation. This review summarizes the discovery, distribution, and function
      of MafA and MafB in rodent pancreatic beta cells, and describes some key
      questions regarding their importance to beta cells.

PMID- 21719307
TI  - Exploring power and sexual decision making among young Latinos residing in rural
      communities.
AB  - BACKGROUND: Studies of relationship power and sexual decision making related to
      contraceptive and condom use among Latinos in the United States are limited. This
      exploratory study provides insight into relationship power and reproductive
      decision making among a sample of young Latinos (n = 58) who live in rural
      communities in the Northwest. METHODS: Using mixed methods approaches, we
      explored through in-depth interviews how Latino men and women define power, what
      makes them feel powerful, who has power, and who makes reproductive decisions
      within their sexual relationships. RESULTS: Descriptions of power and what makes
      Latinos feel powerful in their relationships reflected more widely accepted
      definitions and theories with important distinctions. Participants endorsed
      traditional domains of relationship power describing power as decision-making
      dominance and relationship control. However, smaller proportions of participants
      also described power as shared through joint decision making and equality. Themes
      related to the role of communication and relationship qualities also emerged.
      Based on quantitative measures, men and women reported that men have more
      relative power in relationships yet both reported high degrees of power within
      their own relationships. The majority of women and men believe that both members
      of a couple participated in decisions to use something to prevent pregnancy and
      to use condoms. CONCLUSION: Results underscore that young men and women in new
      settlement areas have traditional views of power while also identifying equality
      and interpersonal qualities to be important components of power dynamics within
      relationships. These findings have important implications for future research and
      the development of pregnancy and HIV/sexually transmitted infection prevention
      programs.

PMID- 21719308
TI  - Age-associated vasospasm in aneurysmal subarachnoid hemorrhage.
AB  - The relationship between age and vasospasm caused by subarachnoid hemorrhage
      (SAH) is controversial. We evaluated this relationship in a contemporary sample
      from a single institution. In a retrospective study design, we included patients
      with SAH caused by ruptured intracranial aneurysms. All patients underwent an
      evaluation that included head imaging, cerebral angiography, and treatment for
      the underlying aneurysm. Vasospasm was classified as absent, any vasospasm, or
      symptomatic vasospasm. Age was classified into 2 categories with a cutoff of 50
      years, and also was stratified by decade. All patients had received preventative
      and therapeutic measures for vasospasm. Logistic regression analysis was used to
      assess the association between age and the occurrence of vasospasm. A total of
      108 patients were included in this analysis, 67 of whom were age >=50 years. The
      older patients had a higher incidence of vascular risk factors, and the younger
      patients had a higher incidence of smoking and illicit substance abuse. The mean
      age of the patients with any vasospasm (n = 41) was 48.51 +/- 11.23 years,
      compared with 59.67 +/- 13.30 years in those without vasospasm (P < .0001).
      Adjusted analysis found a greater risk of vasospasm in the younger patients
      compared with the older patients (odds ratio, 5.83; 95% confidence interval, 2.41
      14.12 for any vasospasm; odds ratio, 2.66; 95% confidence interval, 1.008-7.052
      for symptomatic vasospasm). This risk of vasospasm decreased with advanced age (P
      < .0001). Our findings suggest that patients age <50 years are at 5-fold greater
      risk of any vasospasm compared with older patients, and that age-adjusted
      prevention protocols may need to be considered.

PMID- 21719309
TI  - Acute care and long-term mortality among elderly patients with intracerebral
      hemorrhage who undergo chronic life-sustaining procedures.
AB  - Little is known about patients with intracerebral hemorrhage (ICH) who undergo
      chronic life-sustaining procedures. We sought to explore variations in treatment,
      Medicare payments, and mortality among elderly patients with ICH who received a
      feeding tube, a tracheostomy, or neither chronic life-sustaining procedure.
      Medicare Provider Analysis and Review files from 2004 linked to Center for
      Medicaid and Medicare Services denominator files through January 2005 were
      analyzed. Patients over age 65 years with a primary diagnosis of ICH based on
      discharge code (ICD-9-CM 431) were divided into those who underwent tracheostomy,
      those who underwent feeding tube placement but not tracheostomy, and those who
      underwent neither procedure. Thirty-day and 1-year survival rates were estimated
      using Kaplan-Meier methods. Among the 32,210 patients studied, 6% underwent
      feeding tube placement, and 2.5% underwent tracheostomy. Compared with the
      patients who did not undergo a chronic life-sustaining procedure, those who
      underwent tracheostomy had a longer length of stay (median, 25 days vs 4 days; P
      < .01) and greater Medicare spending (median, $81,479 vs $6,008; P < .01) during
      their initial hospitalization. The 30-day and 1-year cumulative mortality risks
      were 47% and 59%, respectively, in patients who did not undergo a chronic life
      sustaining procedure, 21% and 53% in patients who underwent feeding tube
      placement, and 19% and 65% in those who underwent tracheostomy (P < .01, log-rank
      test across the 3 groups). Our findings show high 1-year mortality among elderly
      patients with ICH, even in those who undergo chronic life-sustaining procedures.
      Medicare payments for patients who undergo tracheostomy are substantial. More
      information about functional outcomes is needed.

PMID- 21719310
TI  - Neural correlates and causal mechanisms.
AB  - What Joseph Neisser calls for is exactly right: more philosophy of science will
      help us better understand and refine the idea of neural correlates of
      consciousness (NCC). But (i) the key bit of philosophy of science Neisser appeals
      to is itself in need of clarification; (ii) the orthodox NCC definition is more
      resourceful than Neisser allows, and (iii) it is possible to resist the
      phenomenological conception of conscious experience that fuels some of Neisser's
      argument.

PMID- 21719311
TI  - Glenoid component loosening due to deficient subscapularis: a case study of
      eccentric loading.

PMID- 21719312
TI  - Total shoulder replacement surgery with custom glenoid implants for severe bone
      deficiency.
AB  - BACKGROUND: Treatment of patients with shoulder arthritis and severe glenoid bone
      loss is controversial. Medial and posterior bone loss limits the size of the
      glenoid vault, which is the structural support of all current glenoid designs.
      This study presents short-term outcomes of a treatment using inset glenoid
      implants during shoulder replacement surgery in deficient glenoid bone. METHODS:
      This study presents short-term outcomes of total shoulder replacement surgery
      using custom inset glenoid implants in deficient glenoid bone. Seven consecutive
      patients (3 men, 4 women; mean age 70 years) treated with inset glenoid implants
      for severe bone deficiency were retrospectively evaluated at a minimum 3-year
      follow-up. Severely deficient bone was defined by a neutral glenoid vault depth
      of less than 15 mm. No bone grafts were used. All patients were evaluated before
      and after surgery with physical examination, radiographic studies, and outcome
      measures. All patients had a diagnosis of osteoarthritis. No patients had rotator
      cuff tears or a history of instability. RESULTS: No surgical complications
      occurred. At an average of 4.3 years, the mean American Shoulder and Elbow
      Surgeon score improved 68 points. There were statistically significant
      improvements in range of motion (forward flexion 33 degrees , external rotation
      34 degrees , internal rotation 6 spinal levels) and in pain (6.9 to 0.1).
      Independent radiographic analysis determined all implants were classified as "low
      risk" for glenoid loosening. DISCUSSION: The treatment of shoulder arthritis with
      severe glenoid bone loss is controversial and the results are mixed. Current
      treatments consist of hemiarthroplasty with or without glenoid reaming, total
      shoulder replacement without version correction, and total shoulder replacement
      with bulk bone grafting and version correction. The surgical technique and
      clinical results described in this case series demonstrate a novel approach of
      inset glenoid fixation for severely deficient bone. CONCLUSIONS: This study
      documents for the first time the possibility of safely and effectively using
      inset glenoid implants to reconstruct deficient bone for which standard implants
      are contraindicated.

PMID- 21719313
TI  - Prospective evaluation of arthroscopic rotator cuff repairs at 5 years: part I-
      functional outcomes and radiographic healing rates.
AB  - BACKGROUND: A rotator cuff registry was established to prospectively evaluate the
      effectiveness of all-arthroscopic repairs. This study reports those results at 5
      years. MATERIALS AND METHODS: The study enrolled 193 patients who underwent all
      arthroscopic rotator cuff repairs. Patients were evaluated preoperatively and at
      1, 2, and 5 years postoperatively. Outcome measurements included the American
      Shoulder and Elbow Surgeons (ASES) score, range of motion, manual muscle testing,
      and ultrasonography. RESULTS: At 5-years, 106 patients completed follow-up,
      representing 55% of the patients originally enrolled but 77% of those who
      returned for evaluation at 1 year. ASES scores improved from 52.6 +/- 23.2
      preoperatively to 92.6 +/- 14.8 at 5 years (P < .001). Paired analyses showed no
      differences between the ASES scores at 2 and 5 years, but the scores improved
      from 1 to 5 years (P = .002). Between years 2 and 5, passive forward elevation
      decreased from 173 degrees  +/- 10.3 degrees  to 168.6 degrees  +/- 16.8 degrees 
      (P = .02) and external rotation decreased from 73.6 degrees  +/- 21.3 degrees  to
      67.8 degrees  +/- 19.6 degrees  (P = .04). Patients improved a full motor grade
      in forward elevation and external rotation and this remained stable over time.
      The healing rates for all patients were 64.3% at 1 year, 75.4% at 2 years, and
      81.2% at 5 years. Paired analyses showed increased healing rates from 1 to 5
      years (P = .001) and from 2 to 5 years (P = .05). DISCUSSION: The midrange
      results of all-arthroscopic rotator cuff repairs are good, and functional results
      remain constant over 5 years. The ultrasound healing rates continued to increase
      with time; however, the mechanism and the clinical significance of this are
      uncertain at this time.

PMID- 21719314
TI  - Outcomes of tendon fractional lengthenings to improve shoulder function in
      patients with spastic hemiparesis.
AB  - BACKGROUND: Patients with spastic hemiparesis after upper motor neuron (UMN)
      injury often exhibit limited shoulder movement. We evaluated the outcomes of
      shoulder tendon fractional lengthenings in patients with spasticity and preserved
      volitional control. METHODS: A consecutive series of 34 adults with spastic
      hemiparesis from UMN injury (23 post-stroke, 11 post-traumatic brain injury) and
      limited shoulder movement with preserved volitional motor control who underwent
      shoulder tendon fractional lengthenings (pectoralis major, latissimus dorsi,
      teres major) were evaluated. Active and passive shoulder motion, spasticity,
      pain, and satisfaction were considered pre- and postoperatively. RESULTS: There
      were 15 males and 19 females with a mean age of 44.1 years. Mean follow-up was
      12.2 months. Mean Modified Ashworth spasticity score was 2.4 preoperatively
      compared to 1.9 postoperatively (P = .001). Active flexion, abduction, and
      external rotation improved compared to the normal contralateral side (P < .001)
      with most dramatic gains in external rotation. Similarly, passive extension,
      flexion, abduction, and external rotation improved compared to the normal
      contralateral side (P < .01). Ninety-four percent (15/16) with preoperative pain
      had improved pain relief postoperatively with 14 (88%) being pain-free. Thirty
      one (92%) were satisfied with the outcome. CONCLUSION: Shoulder tendon
      lengthenings can be an effective means of pain-relief, improved motion, enhanced
      active motor function, and decreased spasticity in patients with spastic
      hemiparesis from UMN injury.

PMID- 21719315
TI  - Long-term subscapularis strength assessment after Bristow-Latarjet procedure:
      isometric study.
AB  - BACKGROUND: The subscapularis is the strongest rotator cuff muscle. Bristow
      Latarjet procedure may impair subscapularis function. The aim of the study is to
      describe the difference in isometric subscapularis (SSC) strength after L-shape
      tenotomy versus muscle split in patients who underwent to Bristow-Latarjet
      procedure. MATERIALS AND METHODS: From 2000 to 2006, we enrolled 376 patients for
      Bristow-Latarjet procedures. We identified 2 groups according to the
      subscapularis approach. Group A included 264 subjects with subscapularis L shape
      tenotomy; group B included 112 subjects with subscapularis muscle split. The
      subscapularis function was assessed with lift-off and belly-press tests.
      Isometric strength of rotator cuff muscle was assessed at an average follow-up of
      45 months in group A and 42 months in group B, recording the maximum isometric
      peak torque (PT) (N), maximum isometric couple (Nm), relative strength index
      (N/Kg), strength, couple and external/internal rotator ratio. Constant and Rowe
      were used as scores. RESULTS: Subscapularis assessment in the overall population
      showed 33 cases (8.8%) with a positive Lift-off test and 30 cases (8%) with a
      positive belly-press test. Rowe and Constant scores increased in both groups (P <
      .01). The mean PT in group A was lower of 24,8 Nw than group B (P < .01);
      similarly, the max PT values of group A were lower of 26.1 Nw than group B (P <
      .01). CONCLUSION: L-shaped tenotomy in Bristow-Latarjet procedure has a weakening
      effect on the subscapularis and for these reasons we strongly recommend the
      muscle split approach for an optimal subscapularis function recovery.

PMID- 21719316
TI  - The effect of capsular repair, bone block healing, and position on the results of
      the Bristow-Latarjet procedure (study III): long-term follow-up in 319 shoulders.
AB  - BACKGROUND: We evaluated the results of the May modification of the Bristow
      Latarjet procedure ("coracoid in standing position") in 319 shoulders with
      respect to (1) coracoid healing and position and (2) surgical treatment of the
      joint capsule. METHODS: From 1980 until 2004, all shoulders with a Bristow
      Latarjet repair were registered at our hospital. This study consists of 3
      different cohorts with respect to follow-up. Series 1, 118 shoulders operated on
      during 1980 through 1985, had 15 years' radiographic and clinical follow-up.
      Series 2, 167 shoulders that had surgery during 1986 through 1999, underwent
      retrospective follow-up by a questionnaire and scores--Western Ontario Shoulder
      Instability Index; Disabilities of the Arm, Shoulder and Hand; and Subjective
      Shoulder Value--after 10 to 23 years. Series 3, 34 shoulders treated during 2000
      through 2004, with an added modified Bankart repair ("capsulopexy") in 33
      shoulders, were prospectively followed up for 5 to 8 years with the same
      questionnaire and scores as series 2. RESULTS: Of 319 shoulders, 16 (5%) had 1 or
      more redislocations and 3 of these (1%) had revision surgery because of remaining
      instability. One or more subluxations were reported in 41 shoulders (13%). The
      worst scores were found in 16 shoulders with 2 or more subluxations (P < .001).
      Radiographs showed bony healing in 246 of 297 shoulders (83%), fibrous union in
      34 (13%), migration by 0.5 cm or more in 14 (5%), and no visualization in 3 (1%).
      Five of six shoulders that had the transplant positioned 1 cm or more medial to
      the glenoid rim had redislocations (83%, P = .001). Shoulders with migrated
      transplants did not differ from those with bony or fibrous healing with respect
      to redislocations and subluxations. When just a horizontal capsular shift was
      added to the transfer, the recurrence rate (redislocations or subluxations)
      decreased, with 2 of 53 (4%)compared with 37 of 208 (18%) with just anatomic
      closure of the capsule (P = .005), and the Western Ontario Shoulder Instability
      Index score improved (92 vs 85.6, P = .048). In total, for 307 of 319 shoulders
      (96%), patients were satisfied or very satisfied at final follow-up. CONCLUSION:
      The open Bristow-Latarjet procedure yields good and consistent results, with bony
      fusion of the coracoid in 83%. A position of the coracoid 1 cm or more medial to
      the rim meant significantly more recurrences. The rate of recurrences decreased
      and subjective results improved when a horizontal capsular shift was added to the
      coracoid transfer.

PMID- 21719317
TI  - Irreparable spontaneous deltoid rupture in rotator cuff arthropathy: the use of a
      reverse total shoulder replacement.

PMID- 21719318
TI  - Subscapularis tenotomy versus lesser tuberosity osteotomy during total shoulder
      replacement: a comparison of patient outcomes.
AB  - BACKGROUND: Two different techniques to release the subscapularis during total
      shoulder replacement (TSR) have been described: tenotomy and osteotomy. We review
      the clinical outcomes of a sequential series of patients in whom a TSR for
      primary osteoarthritis had been performed by either technique at our institution.
      Subscapularis function was tested by a new graded belly-press test. MATERIALS AND
      METHODS: All patients who underwent surgery between January 2002 and January
      2010, and met the eligibility criteria, were included for analysis. Subscapularis
      function was assessed postoperatively with a range of functional assessments,
      including the graded belly-press test and lift-off test, as well as assessment of
      each patient's range of movement. RESULTS: A total of 36 shoulders in 36 patients
      were subsequently reviewed, 10 of whom underwent tenotomy and 26 of whom
      underwent osteotomy. Patients who had undergone osteotomy of the lesser
      tuberosity had a more favorable outcome overall. These patients showed a trend
      toward a better range of movement, although no statistical significance was
      shown. They had a better grade (grade 1) on the belly-press test compared with
      the tenotomy group (P = .026). All patients (osteotomy and tenotomy) with a grade
      1 belly-press test had a better clinical outcome with data showing statistical
      significance. CONCLUSION: Our results indicate that in this single-surgeon
      sequential series, patients who underwent osteotomy of the lesser tuberosity
      during TSR for osteoarthritis had a better functional outcome than those who had
      a subscapularis tenotomy as assessed by the graded belly-press test.

PMID- 21719319
TI  - Prospective evaluation of arthroscopic rotator cuff repairs at 5 years: part II-
      prognostic factors for clinical and radiographic outcomes.
AB  - BACKGROUND: A rotator cuff registry was established to prospectively evaluate the
      effectiveness of all-arthroscopic repairs. The purpose of this study is to report
      prognostic factors for successful clinical and radiographic outcomes at 5 years.
      METHODS: One-hundred ninety-three patients underwent all-arthroscopic rotator
      cuff repairs. Pre- and intraoperative data were compared to the American Shoulder
      and Elbow Surgeon (ASES) score, range of motion, muscle strength, and ultrasound
      results at 5 years using univariate, and multivariate analyses. RESULTS: At 5
      years, 106 patients completed follow-up. There were no pre- or intraoperative
      variables that were predictive of an ASES score >90. Factors predictive of a
      radiographic defect were larger size of the lesion (OR 1.72, 95% CI 1.04-2.85, P
      = .03), multiple tendon involvement (OR 5.56, 95% CI 1.23-25.22, P = .02), older
      age (OR 1.15, 95% CI 1.04-1.28, P = .01), concomitant biceps (OR 16.16, 95% CI
      3.01-86.65, P = .001), and acromioclavicular joint procedures (OR 6.70, 95% CI
      1.46-30.73, P = .01). Radiographic healing did not correspond to clinical
      outcomes. Resolution of a radiographic defect was seen in 14 patients. Younger
      age (OR 0.84, 95% CI 0.74-0.95, P = .004) and single-tendon tears (OR 7.59, 95%
      CI 1.71-84.45, P = .04) were predictive. DISCUSSION: Larger tears in older
      patients who undergo concomitant procedures are predictive of radiographic
      defects at 5 years; however, radiographic healing did not correspond to clinical
      results. Younger patients with single tendon tears are more likely to undergo
      spontaneous resolution of a radiographic defect. This information can be useful
      in counseling patients regarding the mid-term results of this procedure.

PMID- 21719320
TI  - Apprenticeships ease the transition to independent call: an evaluation of anxiety
      and confidence among junior radiology residents.
AB  - RATIONALE AND OBJECTIVES: The aims of this study were to quantify resident
      anxiety when beginning independent call and to assess whether an apprenticeship
      experience (buddy call) can lessen anxiety and improve confidence. MATERIALS AND
      METHODS: A prospective cohort comparison of two groups of radiology residents
      beginning independent call, one of which was provided with a buddy call
      experience, was performed. Anxiety and confidence were assessed using the Endler
      Multidimensional Anxiety Scales-State (EMAS-S), with total score, autonomic
      emotional, and cognitive worry components, and a five-point, Likert-type scale,
      respectively. Both groups were asked about the perceived value of a buddy call
      experience. RESULTS: EMAS-S scores improved significantly over 5 days of call in
      both groups (control, n = 10, P = .0005; buddy call, n = 9, P = .0001), and image
      interpretation confidence correspondingly increased (control, P = .0004; buddy
      call, P = .003). Compared to the control group, autonomic emotional scores were
      significantly lower in the buddy call group on the first day of independent call
      (P = .040), and cognitive worry and total EMAS-S scores were significantly lower
      on day 5 (both P values = .03). Buddy call was independently associated with
      improved autonomic emotional and film interpretation confidence scores (both P
      values = .02). All members of the buddy call group indicated that the experience
      was very helpful in preparing for call. CONCLUSIONS: Beginning independent call
      is associated with high anxiety, and buddy call reduces that anxiety, beyond the
      effect of time alone. Residents who participated in buddy call found it helpful
      in preparing for independent call. These findings support the use of buddy call
      and tiered call structures as means to introduce junior residents to independent
      call.

PMID- 21719321
TI  - Evaluation of combined oncologic and functional outcomes after robotic-assisted
      laparoscopic extraperitoneal radical prostatectomy: trifecta rate of achieving
      continence, potency and cancer control.
AB  - OBJECTIVES: Outcomes of continence, erectile function, and oncologic control are
      well-described in isolation especially for the retropubic open approach. However,
      only few series have yet reported combined results after radical prostatectomy.
      To determine the proportion of men who are continent, potent, and cancer-free
      (trifecta rate) 2 years after robot-assisted laparoscopic radical prostatectomy
      (RALRP). MATERIALS AND METHODS: We included patients who underwent a RALRP at our
      department and who were followed during at least 2 years. Men who were impotent
      or incontinent before the surgery were excluded from the analysis. Overall, 500
      men were included. All patients prospectively completed validated questionnaires
      (IIEF-5, ICS) before the medical visit and concerning their voiding and sexual
      disorders, preoperatively, 3, 6, 12, 18, and 24 months after RALRP. Biochemical
      recurrence was defined as any detectable serum PSA (>= 0.2 ng/ml). The study end
      point was the trifecta rate (cancer control, continence, and potency) at 2 years
      of the surgery. Predictive factors of the trifecta outcome were assessed in
      univariate and multivariate analyses. RESULTS: Median age and PSA level were 62.2
      years and 9.7 ng/mL. A trifecta outcome was achieved in 44% and 53% of men at 12
      and 24 months, respectively. The 2-year trifecta rate reached 62% in men
      undergoing bilateral nerve-sparing surgery and 71% in men < 60 years. Age < 60
      years, PSA level < 10 ng/ml, organ-confined disease, and bilateral nerve-sparing
      procedure were significantly associated with the 2-year trifecta outcome.
      CONCLUSION: Two years after RALRP, the trifecta outcome is achieved in 53% of
      preoperatively potent and continent men.

PMID- 21719322
TI  - Complications of laparoscopic partial nephrectomy.
AB  - OBJECTIVES: We report our experience with laparoscopic partial nephrectomy (LPN)
      to identify preoperative factors associated with an increased risk of
      postoperative complications. MATERIALS AND METHODS: Among patients undergoing
      LPN, we analyzed demographic and preoperative tumor characteristics as the
      exposure variables and postoperative complications as the outcomes. Multivariable
      logistic regression modeling identified variables associated with increased risk
      of complications. RESULTS: Of 336 consecutive patients undergoing LPN, 120
      (35.7%) had a complication, including 22 (6.6%) with major complications, 12
      (3.6%) developing urine leak, 29 (8.6%) requiring blood transfusion, and 11
      (3.3%) undergoing nephrectomy. There were no perioperative deaths. On univariable
      analysis, larger tumor diameter increased the odds of any complication (odds
      ratio [OR] 2.3, P = 0.007), hemorrhage (OR 1.4, P = 0.007), and urine leak (OR
      1.7, P = 0.001). Each 1 cm increase in tumor diameter was associated with a 33%
      increased odds of a major complication (P = 0.04). In a multivariable model,
      changes in tumor diameter increased the odds of any complication (OR 2.4, P =
      0.006) and hemorrhage (OR 1.5, P = 0.01); tumor depth was a better predictor of a
      major complication (OR 1.1, P = 0.004). In the multivariable model, advanced age
      also was associated with hemorrhage (OR 2.6, P = 0.05). CONCLUSIONS: Tumor
      diameter, depth of tumor penetration, and advanced patient age are associated
      with increased odds of complications in patients undergoing LPN. This information
      is important for counseling patients preoperatively regarding their risk of
      complications following LPN and in selecting the appropriate intervention for a
      particular tumor.

PMID- 21719323
TI  - Elimination of preoperative mechanical bowel preparation in patients undergoing
      cystectomy and urinary diversion.
AB  - INTRODUCTION: The utility of a preoperative mechanical bowel preparation prior to
      bowel surgery has recently been questioned. The purpose of this study is to
      compare the perioperative outcomes between patients undergoing cystectomy with
      urinary diversion with or without preoperative mechanical bowel preparation.
      METHODS: Seventy patients underwent radical cystectomy and urinary diversion
      between May 2008 and August 2009 for bladder cancer. The first cohort of patients
      (n = 37) underwent cystectomy and diversion during the period May 2008-December
      2008 and underwent a preoperative mechanical bowel preparation including a clear
      liquid diet, magnesium citrate solution, and an enema before surgery. The second
      cohort of patients underwent surgery during the period of January 2009-August
      2009 (n=33). These patients were given a regular diet before surgery and did not
      undergo a mechanical bowel preparation except for the enema before surgery was
      performed to decrease rectal/colonic distention. Outcome measures included
      gastrointestinal and overall complications, and perioperative outcomes including
      recovery of bowel function. RESULTS: There were no differences with regard to
      recovery of bowel function, time to discharge, or overall complication rates
      between the 2 groups. More specifically, the rate of GI complications was not
      different in prepped patients vs. nonprepped patients (22% vs. 15%; P = 0.494).
      There were no occurrences of bowel anastomotic leak, fistula, abscess,
      peritonitis, or surgical site infection in either group. One perioperative death
      occurred in the nonprepped group secondary to cardiovascular complications.
      CONCLUSIONS: Preoperative mechanical bowel preparation prior to radical
      cystectomy with urinary diversion does not demonstrate any significant advantage
      in perioperative outcomes, including gastrointestinal complications. Further
      studies aimed at measuring patient satisfaction and larger randomized trials will
      be beneficial in evaluating the role of mechanical bowel preparation prior to
      urinary diversion.

PMID- 21719324
TI  - Early continence in patients with localized prostate cancer. A comparison between
      open retropubic (RRPE) and endoscopic extraperitoneal radical prostatectomy
      (EERPE).
AB  - OBJECTIVE: The study examined and compared continence rates in prostate cancer
      patients who had undergone either open retropubic prostatectomy (RRPE) or
      endoscopic extraperitoneal radical prostatectomy (EERPE). The core question was
      whether the surgical approach had an effect on the patients' continence status 3
      months after surgery. METHODS: We conducted a multicentric, longitudinal study in
      7 German hospitals. Three hundred fifty prostate cancer patients (166 EERPE, 184
      RRPE) were asked to self-assess symptoms associated with urinary incontinence
      (UI) 1 day before and 3 months after prostatectomy. Symptoms of UI were assessed
      using the EORTC QLQ-PR25 questionnaire. Urinary continence was defined according
      to (1) the use of no protective pad, (2) the use of up to a single protective pad
      in a 24-hour period, and (3) according to the patient's self-assessment. A binary
      regression model was employed to predict early continence status. RESULTS: Three
      months after prostatectomy, 44% of patients who underwent EERPE and 40% of
      patients who underwent RRPE were completely continent. Patients who underwent
      nerve-sparing prostatectomy and patients younger than 65 years had a better
      chance of regaining urinary continence earlier. The surgical approach had no
      significant impact on the patients' continence status. Limitations of the study
      are a drop-out rate of 39% and sociodemographic and clinical differences between
      both treatment groups. CONCLUSIONS: Three months after prostatectomy, there were
      no significant differences between both treatment groups regarding urinary
      continence. The surgical approach had no significant effect on the patients'
      continence status. Higher age and non-nerve-sparing surgery are associated with a
      longer period of convalescence.

PMID- 21719325
TI  - Tumor volume, surgical margin, and the risk of biochemical recurrence in men with
      organ-confined prostate cancer.
AB  - OBJECTIVES: We proposed to investigate predictors of biochemical recurrence (BCR)
      in pT2 prostate cancer by identifying the interrelationship between the tumor
      volume and surgical margin status, and their impact on recurrence. MATERIALS AND
      METHODS: Clinical, pathologic, and follow-up data of 404 consecutive patients who
      were treated with radical prostatectomy alone and were diagnosed as pT2 prostate
      cancer in our institution were reviewed. Percent tumor volume (PTV) was estimated
      from the cancer distribution map, and the surgical margin status was reviewed by
      a single pathologist (JYR). Clinicopathologic variables were analyzed with
      respect to the risk of BCR. RESULTS AND LIMITATIONS: Recurrence was observed in
      39 (9.7%) patients at a mean of 28.9 (5-47) months. Preoperative PSA, biopsy
      Gleason score, surgical Gleason score, PTV, and surgical margin status were
      significantly related to BCR in univariate analysis; in multivariate analysis,
      PTV (P < 0.001) and surgical Gleason score (P = 0.021) were independent
      predictors of BCR. PTV was also an independent determinant of positive surgical
      margin (P = 0.035, HR 1.026, 95% CI 1.002-1.050). By combining the 2 predictors 5
      year recurrence-free survivals for PTV <= 14.5% and surgical Gleason score <= 7,
      PTV >14.5% or surgical Gleason score > 7, and PTV > 14.5% and surgical Gleason
      score > 7 were 97.5%, 88.7%, and 44.5%, respectively (log-rank test, P < 0.01).
      Retrospective study nature, use of PTV instead of actual volume, and intermediate
      follow-up length are the main limitations of the study. CONCLUSIONS: In men with
      pT2 prostate cancer, percent tumor volume and the surgical Gleason score were
      independently prognostic of BCR and by combining the 2 factors, risk of BCR could
      be significantly stratified. Tumor volume further determined surgical margin
      status undermining its prognostic value as an independent variable.

PMID- 21719326
TI  - Renal tumors in solid organ recipients: clinical and pathologic features.
AB  - OBJECTIVES: Solid organ recipients are several times more likely to develop renal
      cell carcinoma (RCC) compared with the general population, but little is known
      about the features of these tumors. The aim of this study is to report on the
      characteristics of renal tumors in solid organ recipients compared with the
      general population. MATERIALS AND METHODS: Patients undergoing surgery for a
      localized renal mass between 2000 and 2008 were studied. Demographic, clinical,
      radiographic, and pathologic characteristics were compared between patients with
      and without a history of organ transplant. A subanalysis focused on the features
      of a kidney compared with another non-renal organ transplant. RESULTS: Of 950
      patients identified, 19 were organ recipients. Transplant recipients were younger
      and had lower body mass indices. Most organ recipients (94.7%) were asymptomatic
      at presentation. Transplant recipients had higher incidence of malignant
      pathology (88.2% vs. 78.7%), but had smaller masses, of lower stage and grade,
      and a higher proportion of papillary histology (35.3% vs. 19.8%). Papillary
      subtype accounted for almost one-half of the RCCs in kidney recipients compared
      with 20% in other organ recipients. Over a median follow-up of 4 years, 1 (5.9%)
      local recurrence, no metastatic progressions, and no RCC-related deaths occurred
      in the transplant cohort. CONCLUSIONS: Organ recipients typically present with
      incidental renal masses of smaller size. However, these are twice more likely to
      be malignant compared with the general population. RCC arising in transplant
      recipients tend to be of lower stage and grade, contributing to the apparently
      excellent oncologic outcomes of surgical treatment.

PMID- 21719327
TI  - Limitation of mouth opening caused by osteochondroma of the coronoid process.
AB  - BACKGROUND: Osteochondroma at the level of the coronoid process is unusual,
      causing a slowly progressive facial asymmetry and limitation of mouth opening.
      Histologically, it is a bone tumor covered by a thin capsule of cartilage. We
      present a literature review of cases published to date and present a new case in
      which osteochondroma originating in the coronoid process was associated with the
      formation of a cyst at the body of the zygoma, necessitating the reconstruction
      of the body of the zygoma. STUDY DESIGN: A 55-year-old woman had a bone tumor in
      the right malar region, producing a limitation in mouth opening. After
      preoperative computerized tomography, we decided to excise the lesion and
      pseudocyst with the use of a combined subciliary and coronal approach,
      reconstructing the body of the zygoma with a cortical chip of calvarian bone.
      RESULTS: The patient regained normal mouth opening, without injury to the fronto
      orbital branches of the facial nerve and no recurrence of the tumor to date.
      CONCLUSIONS: Osteochondroma is a slow-growing tumor that causes progressive
      facial asymmetry and limitation of mouth opening. The treatment of choice for
      symptomatic osteochondromas is surgical resection.

PMID- 21719328
TI  - Teenage sexuality in different cultures.

PMID- 21719329
TI  - The association between health care professional attitudes and beliefs and the
      attitudes and beliefs, clinical management, and outcomes of patients with low
      back pain: a systematic review.
AB  - BACKGROUND: It has been suggested that health care professional (HCP) attitudes
      and beliefs may negatively influence the beliefs of patients with low back pain
      (LBP), but this has not been systematically reviewed. This review aimed to
      investigate the association between HCP attitudes and beliefs and the attitudes
      and beliefs, clinical management, and outcomes of this patient population.
      METHODS: Electronic databases were systematically searched for all types of
      studies. Studies were selected by predefined inclusion criteria. Methodological
      quality was appraised and strength of evidence was determined. RESULTS: Seventeen
      studies from eight countries which investigated the attitudes and beliefs of
      general practitioners, physiotherapists, chiropractors, rheumatologists,
      orthopaedic surgeons and other paramedical therapists were included. There is
      strong evidence that HCP beliefs about back pain are associated with the beliefs
      of their patients. There is moderate evidence that HCPs with a biomedical
      orientation or elevated fear avoidance beliefs are more likely to advise patients
      to limit work and physical activities, and are less likely to adhere to treatment
      guidelines. There is moderate evidence that HCP attitudes and beliefs are
      associated with patient education and bed rest recommendations. There is moderate
      evidence that HCP fear avoidance beliefs are associated with reported sick leave
      prescription and that a biomedical orientation is not associated with the number
      of sickness certificates issued for LBP. CONCLUSION: HCPs need to be aware of the
      association between their attitudes and beliefs and the attitudes and beliefs and
      clinical management of their patients with LBP.

PMID- 21719330
TI  - Musculoskeletal pain and use of analgesics in relation to mobility limitation
      among community-dwelling persons aged 75 years and older.
AB  - Pain and factors related to it constitute serious health problems in the older
      population. This populationbased cross-sectional study aimed to investigate
      whether musculoskeletal pain is associated with mobility limitation and whether
      the relationship between pain and mobility limitation varies according to the use
      of analgesics among community-dwelling older people. A total of 622 community
      dwelling participants aged 75 years and older (mean age 80.4, 74% women) were
      interviewed about presence and severity of musculoskeletal pain. Self-reported
      analgesic drug utilization was verified against medical records. Mobility
      limitation was assessed by the Timed Up & Go test (TUG) time of >13.5 s or
      inability to perform the test. Logistic regression was used to evaluate the pain
      affect associations, with associations expressed as odds ratios with 95%
      confidence intervals (CI). After adjustment for several covariates,
      musculoskeletal pain remained independently associated with mobility limitation
      (odds ratio = 1.83; 95% CI 1.16, 2.89). The risk of mobility limitation was
      highest among those who reported severe or moderate pain (1.84; 1.13, 3.13) and
      among those who used analgesics (2.37; 1.37, 4.11). In conclusion,
      musculoskeletal pain increases the risk for mobility limitation. The present
      findings underline the importance of the careful assessment and pharmacological
      and nonpharmacological management of pain in promoting mobility in older age.

PMID- 21719332
TI  - Feline cholangitis: a necropsy study of 44 cats (1986-2008).
AB  - Forty-four cats diagnosed with moderate to severe cholangitis at necropsy are
      described. The population comprised 0.86% of all feline necropsies performed
      during the 22-year study period. Liver specimens were classified as acute
      neutrophilic cholangitis (ANC), chronic neutrophilic cholangitis (CNC),
      lymphocytic cholangitis (LC) or chronic cholangitis associated with liver fluke
      infestation (CC) based on the World Small Animal Veterinary Association (WSAVA)
      classification scheme. ANC (seven) and CNC (33) comprised the majority of cases.
      In contrast to previous descriptions, overlap was seen in clinical findings
      between ANC and CNC subtypes. Results suggest that liver enzyme activity may not
      predict degree of inflammation. Severity of inflammation varied between liver
      sections in individual cats, underscoring the need to obtain biopsy samples from
      multiple sites. Inflammatory bowel disease (50%), pancreatitis (60%), or both
      (32%) commonly accompanied cholagitis. We conclude that cholangitis is not a
      common cause of feline mortality. Most cats that succumb to cholangitis have ANC
      or CNC, and concurrent disease contributes to death in many.

PMID- 21719333
TI  - Refeeding syndrome in a cat with hepatic lipidosis.
AB  - Refeeding syndrome is characterized by severe hypophosphatemia occurring in
      patients given enteral or parenteral nutrition after severe weight loss. There
      are few veterinary reports that describe this syndrome but it is well documented
      in human medicine. This report describes a case of a domestic shorthair cat
      diagnosed with hepatic lipidosis following a 4-week history of decreased appetite
      and weight loss and in whom refeeding syndrome was documented after initiation of
      enteral nutrition. Clinical findings, blood work abnormalities and disease
      progression in this patient are described from the time of diagnosis through to
      recovery. A review of the current literature pertinent to this clinical syndrome
      is included.

PMID- 21719334
TI  - [Anxiety of nursing staff in the face of death in critical care units and its
      relationship with the patients' age].
AB  - INTRODUCTION: Death is a biological and psychosocial process, in which many of
      the vital events extinguish in a gradual and silent sequence, this escaping
      simple observation. People live with the fear of death, however health care
      professionals are constantly faced with the death of other people and in
      continuous contact with this. This may negatively or positively affect their
      attitudes. OBJECTIVE: To assess anxiety levels of the intensive care unit nurses
      in the face of death. MATERIAL AND METHOD: This is an observational, descriptive
      cross-sectional study conduced in the Pediatric and Adult Intensive Care Unit
      (ICU) of the University Hospital General Gregorio Maranon. A Death Anxiety
      Inventory (DAI) was used for the assessment of anxiety in the presence of death.
      RESULTS: The response rate was 86.9%. Mean age of participants was 38+/-9.25
      years (range, 22-63). Mean working experience was 13+/-7.2 years (range, 35 years
      7 months). The item having the highest level of anxiety was number 14-"I would
      like to live to an advanced age" (n=113; mean, 3.35+/-1.2). Statistically
      significant correlations (p=0.01) were found in the levels of anxiety between
      nurses of pediatric ICU and adult ICU in factor 1-"External generators of
      anxiety", this being higher in the pediatric ICU. A total of 77% of the
      professionals consider they are trained for the subject of death compared to
      18.6% who do not. CONCLUSIONS: The ICU professionals who attend to children have
      higher levels of anxiety and of considering that they are not trained for this
      than those attending adults.

PMID- 21719335
TI  - [What is the real incidence of falls in hospitals?].
AB  - AIMS: To determine the incidence of falls at acute hospital level and to compare
      this incidence with that found in the observational study with the notified
      falls. METHOD: We used a prospective observational study to register patient
      falls, with daily follow-up in the medical-surgical hospital units, and reviewed
      the notification of falls records. The patient monitoring was conducted between
      December 2008 and March 2009 at Fuenlabrada University Hospital. The accumulated
      incidence of falls was calculated, the association between qualitative variables,
      and the validity of the notification of falls record with regards to the
      reference pattern, the observational study. RESULTS: A follow-up has been
      completed 1,001 patients, finding an accumulated incidence of 1.6% of the
      followed-up patients, compared to a notified incidence of 0.9%. No statistically
      significant differences were found (P=.167. The notification of falls record had
      a Kappa index of 0.24, with a sensitivity of 18.75% and a specificity of 99.39%,
      compared to the reference, the observational study. CONCLUSION: The incidence of
      falls practically doubles when using data from observational studies as opposed
      to those from notification systems.

PMID- 21719336
TI  - [Instrumental, communicative and strategic actions: a descriptive study of
      nursing practice according to critical theory].
AB  - AIMS: According to the literature consulted, the biomedical approach continues
      dominating the ways in which nurses think, work and inform. In order to study
      whether this situation also occurs in our context, this research proposes to 1)
      describe the value or weight nurses give to the different instrumental, strategic
      and communicative actions, according to Habermas' Theory of the Communicative
      Action; as well as 2) analyse its possible relationship with the type of unit in
      which nurses work. METHODS: It is a descriptive study including 89 nurses,
      conducted in medical, surgical and onco-haematological hospital wards in the
      Hospital Reina Sofia of Cordoba. For the data collection, a questionnaire was
      created specifically for the study, made up of 4 instrumental actions, 4
      strategic actions and 4 communicative actions that were scored 1-5 according to
      their value or importance. The questionnaire was self-administered and collected
      after one week. RESULTS: The instrumental actions obtain the highest scores in
      the area of thoughts (19.49) and practice (18.9), followed by the communicative
      actions. Nevertheless, the strategic actions exceeded the communicative actions
      in the record (17.27 vs 14.49). Only in the onco-haematology units, communicative
      actions maintained high scores (17.26). CONCLUSIONS: The results from the present
      study emphasise the hegemony of the biomedical model, represented by instrumental
      and strategic actions, and draw a difficult situation for the communicative
      action, which has to find its place in the professional speech.

PMID- 21719337
TI  - Disseminated cutaneous sporotrichosis in an immunocompetent individual.
AB  - Sporotrichosis is a subacute or chronic fungal infection caused by the ubiquitous
      fungus Sporothrix schenckii. Disseminated cutaneous sporotrichosis is an uncommon
      entity and is usually present in the immunosuppressed. Here, a case of
      disseminated cutaneous sporotrichosis in an immunocompetent patient is reported.
      This 70-year-old healthy woman presented with multiple painful ulcerated nodules
      on her face and upper and lower extremities of 6-month duration, associated with
      low-grade fever, night sweats, loss of appetite, and loss of weight.
      Histopathological examination of the skin biopsy revealed epidermal hyperplasia
      and granulomatous inflammation in the dermis, with budding yeast. Fungal culture
      identified S. schenckii. She had total resolution of the lesions after 2 weeks of
      intravenous amphotericin B and 8 months of oral itraconazole. All investigations
      for underlying immunosuppression and internal organ involvement were negative.
      This case reiterates that disseminated cutaneous sporotrichosis, although common
      in the immunosuppressed, can also be seen in immunocompetent patients.

PMID- 21719338
TI  - [Pathogen inactivation in platelet concentrates: the French experience].
AB  - The transfusion of platelet concentrates is increasing in oncohematology patients
      due to chemotherapy and hematopoietic stem cell grafts. The transmission of
      pathogenic agents, viruses, parasites and especially bacteria with platelet
      concentrates stored at room temperature (20-24 degrees C) is associated with a
      septic risk, partly prevented by bacterial detection. Photochemical inactivation
      of platelet concentrates, using a technique associating amotosalen and UVA, has
      been used for five years in a French region for the whole population and a large
      spectrum of patients, with efficacy and safety. Universal implementation of
      pathogen inactivation in labile blood products is a major and key step to improve
      safety against infection in transfusion.

PMID- 21719339
TI  - [Pathogen reduction of blood components: from financial issues to possible long
      term consequences].
AB  - Pathogen inactivation of blood products represents a global and major paradigm
      shift in transfusion medicine. In the next near future, it is likely that most
      blood products will be inactivated by various physicochemical approaches. The
      concept of blood safety will be challenged as well as transfusion medicine
      practice, notably for donor selection or biological qualification. In this
      context, it seems mandatory to develop analytical economic approaches by
      assessing costs-benefits ratio of blood transfusion as well as to set up cohorts
      of patients based on hemovigilance networks allowing rigorous scientific analysis
      of the benefits and the risks of blood transfusion at short- and long-term.

PMID- 21719340
TI  - Modelization of a self-opening peripheral neural interface: a feasibility study.
AB  - In this paper a self-opening intrafascicular neural interface (SELINE) has been
      modeled using both a theoretical approach and a Finite Element (FE) analysis.
      This innovative self opening interface has several potential advantages such as:
      higher selectivity due to its three-dimensional structure and efficient anchorage
      system. Mechanical, structural and micro-technological issues have been
      considered to obtain an effective design of the electrode, as a feasibility study
      of the self-opening approach. A simple framework has been provided to model the
      insertion and partial retraction into peripheral nerves, resulting in the opening
      of wings. This integrated approach results in a rational procedure to optimize
      kinematics, geometry, and structural properties of peripheral interfaces. The
      design and feasibility study carried out in this work can potentially assure a
      correct behavior and dimensioning of the neural interface: in this way anomalous
      breakage should be avoided while mechanical and geometrical biocompatibility
      should increase.

PMID- 21719341
TI  - Phytochrome signaling: solving the Gordian knot with microbial relatives.
AB  - Phytochromes encompass a diverse collection of biliproteins that regulate
      numerous photoresponses in plants and microorganisms. Whereas the plant versions
      have proven experimentally intractable for structural studies, the microbial
      forms have recently provided important insights into how these photoreceptors
      work at the atomic level. Here, we review the current understanding of these
      microbial phytochromes, which shows that they have a modular dimeric architecture
      that propagates light-driven rotation of the bilin to distal contacts between
      adjacent signal output domains. Surprising features underpinning this signaling
      include: a deeply buried chromophore; a knot and hairpin loop that stabilizes the
      photosensing domain; and an extended helical spine that translates conformational
      changes in the photosensing domain to the output domain. Conservation within the
      superfamily both in modular construction and sequence strongly suggests that
      higher plant phytochromes work similarly as light-regulated toggle switches.

PMID- 21719342
TI  - Probabilistic 4D blood flow tracking and uncertainty estimation.
AB  - Phase-Contrast (PC) MRI utilizes signal phase shifts resulting from moving spins
      to measure tissue motion and blood flow. Time-resolved 4D vector fields
      representing the motion or flow can be derived from the acquired PC MRI images.
      In cardiovascular PC MRI applications, visualization techniques such as vector
      glyphs, streamlines, and particle traces are commonly employed for depicting the
      blood flow. Whereas these techniques indeed provide useful diagnostic
      information, uncertainty due to noise in the PC-MRI measurements is ignored,
      which may lend the results a false sense of precision. In this work, the
      statistical properties of PC MRI flow measurements are investigated and a
      probabilistic flow tracking method based on sequential Monte Carlo sampling is
      devised to calculate flow uncertainty maps. The theoretical derivations are
      validated using simulated data and a number of real PC MRI data sets of the aorta
      and carotid arteries are used to demonstrate the flow uncertainty mapping
      technique.

PMID- 21719343
TI  - Automatic segmentation of the wire frame of stent grafts from CT data.
AB  - Endovascular aortic replacement (EVAR) is an established technique, which uses
      stent grafts to treat aortic aneurysms in patients at risk of aneurysm rupture.
      Late stent graft failure is a serious complication in endovascular repair of
      aortic aneurysms. Better understanding of the motion characteristics of stent
      grafts will be beneficial for designing future devices. In addition, analysis of
      stent graft movement in individual patients in vivo can be valuable for
      predicting stent graft failure in these patients. To be able to gather
      information on stent graft motion in a quick and robust fashion, we propose an
      automatic method to segment stent grafts from CT data, consisting of three steps:
      the detection of seed points, finding the connections between these points to
      produce a graph, and graph processing to obtain the final geometric model in the
      form of an undirected graph. Using annotated reference data, the method was
      optimized and its accuracy was evaluated. The experiments were performed using
      data containing the AneuRx and Zenith stent grafts. The algorithm is robust for
      noise and small variations in the used parameter values, does not require much
      memory according to modern standards, and is fast enough to be used in a clinical
      setting (65 and 30s for the two stent types, respectively). Further, it is shown
      that the resulting graphs have a 95% (AneuRx) and 92% (Zenith) correspondence
      with the annotated data. The geometric model produced by the algorithm allows
      incorporation of high level information and material properties. This enables us
      to study the in vivo motions and forces that act on the frame of the stent. We
      believe that such studies will provide new insights into the behavior of the
      stent graft in vivo, enables the detection and prediction of stent failure in
      individual patients, and can help in designing better stent grafts in the future.

PMID- 21719344
TI  - Automatic analysis of diabetic peripheral neuropathy using multi-scale
      quantitative morphology of nerve fibres in corneal confocal microscopy imaging.
AB  - Diabetic peripheral neuropathy (DPN) is one of the most common long term
      complications of diabetes. Corneal confocal microscopy (CCM) image analysis is a
      novel non-invasive technique which quantifies corneal nerve fibre damage and
      enables diagnosis of DPN. This paper presents an automatic analysis and
      classification system for detecting nerve fibres in CCM images based on a multi
      scale adaptive dual-model detection algorithm. The algorithm exploits the
      curvilinear structure of the nerve fibres and adapts itself to the local image
      information. Detected nerve fibres are then quantified and used as feature
      vectors for classification using random forest (RF) and neural networks (NNT)
      classifiers. We show, in a comparative study with other well known curvilinear
      detectors, that the best performance is achieved by the multi-scale dual model in
      conjunction with the NNT classifier. An evaluation of clinical effectiveness
      shows that the performance of the automated system matches that of ground-truth
      defined by expert manual annotation.

PMID- 21719345
TI  - USC-HN2, a new model cell line for recurrent oral cavity squamous cell carcinoma
      with immunosuppressive characteristics.
AB  - Head and neck squamous cell carcinomas (HNSCC) are common and aggressive tumors
      that have not seen an improvement in survival rates in decades. These tumors are
      believed to evade the immune system through a variety of mechanisms and are
      therefore highly immune modulatory. In order to elucidate their interaction with
      the immune system and develop new therapies targeting immune escape, new pre
      clinical models are needed. A novel human cell line, USC-HN2, was established
      from a patient biopsy specimen of invasive, recurrent buccal HNSCC and
      characterized by morphology, heterotransplantation, cytogenetics, phenotype, gene
      expression, and immune modulation studies and compared to a similar HNSCC cell
      line; SCCL-MT1. Characterization studies confirmed the HNSCC origin of USC-HN2
      and demonstrated a phenotype similar to the original tumor and typical of
      aggressive oral cavity HNSCC (EGFR(+)CD44v6(+)FABP5(+)Keratin(+) and HPV(-)).
      Gene and protein expression studies revealed USC-HN2 to have highly immune
      modulatory cytokine production (IL-1beta, IL-6, IL-8, GM-CSF, and VEGF) and
      strong regulatory T and myeloid derived suppressor cell (MDSC) induction capacity
      in vitro. Of note, both USC-HN2 and SCCL-MT1 were found to have a more robust
      cytokine profile and MDSC induction capacity when compared to seven previously
      established HNSCC cell lines. Additionally, microarray gene expression profiling
      of both cell lines demonstrate up-regulation of antigen presenting genes. Because
      USC-HN2 is therefore highly immunogenic, it also induces strong immune
      suppression to evade immunologic destruction. Based upon these results, both cell
      lines provide an excellent model for the development of new suppressor cell
      targeted immunotherapies.

PMID- 21719346
TI  - Effects of voice harmonic complexity on ERP responses to pitch-shifted auditory
      feedback.
AB  - OBJECTIVE: The present study investigated the neural mechanisms of voice pitch
      control for different levels of harmonic complexity in the auditory feedback.
      METHODS: Event-related potentials (ERPs) were recorded in response to+200 cents
      pitch perturbations in the auditory feedback of self-produced natural human
      vocalizations, complex and pure tone stimuli during active vocalization and
      passive listening conditions. RESULTS: During active vocal production, ERP
      amplitudes were largest in response to pitch shifts in the natural voice,
      moderately large for non-voice complex stimuli and smallest for the pure tones.
      However, during passive listening, neural responses were equally large for pitch
      shifts in voice and non-voice complex stimuli but still larger than that for pure
      tones. CONCLUSIONS: These findings suggest that pitch change detection is
      facilitated for spectrally rich sounds such as natural human voice and non-voice
      complex stimuli compared with pure tones. Vocalization-induced increase in neural
      responses for voice feedback suggests that sensory processing of naturally
      produced complex sounds such as human voice is enhanced by means of motor-driven
      mechanisms (e.g. efference copies) during vocal production. SIGNIFICANCE: This
      enhancement may enable the audio-vocal system to more effectively detect and
      correct for vocal errors in the feedback of natural human vocalizations to
      maintain an intended vocal output for speaking.

PMID- 21719347
TI  - Chemotherapy-induced peripheral neurotoxicity in the era of pharmacogenomics.
AB  - Development of advanced and high-throughput methods to study variability in human
      genes means we can now use pharmacogenomic analysis not only to predict response
      to treatment but also to assess the toxic action of drugs on normal cells (so
      called toxicogenomics). This technological progress could enable us to identify
      individuals at high and low risk for a given side-effect. Pharmacogenomics could
      be very useful for stratification of cancer patients at risk of developing
      chemotherapy-induced peripheral neurotoxicity, one of the most severe and
      potentially permanent non-haematological side-effects of modern chemotherapeutic
      agents. However, study data reported so far are inconsistent, which suggests that
      methodological improvement is needed in clinical trials to obtain reliable
      results in this clinically relevant area.

PMID- 21719348
TI  - Abandonment of treatment for childhood cancer: position statement of a SIOP PODC
      Working Group.

PMID- 21719349
TI  - Targeting of Toll-like receptors: a decade of progress in combating infectious
      diseases.
AB  - Toll-like receptors (TLRs) recognise highly conserved molecular structures,
      collectively known as pathogen-associated molecular patterns. In the past two
      decades, development and clinical implementation of TLR ligands-ie, chemically
      modified synthetic derivatives of naturally occurring ligands and fully synthetic
      small molecules-have been topics of intense research. Targeted manipulation of
      TLR signalling has been applied clinically to boost vaccine effectiveness,
      promote a robust T helper 1-predominant immune response against viral infection,
      or dampen the exaggerated inflammatory response to bacterial infection. Use of
      these new therapeutic molecules as adjuncts to conventional pharmacotherapy or
      stand-alone treatments might offer solutions to unmet clinical needs or could
      replace existing partly effective therapeutic strategies.

PMID- 21719350
TI  - Response to commentary by Schneck.

PMID- 21719351
TI  - Association between polymorphisms in serotonin and dopamine-related genes and
      endogenous pain modulation.
AB  - Genetic studies have become indispensable in understanding pain mechanisms,
      shedding light on the role of monoamine pathways in pain modulation. The present
      study was aimed to explore the relationship between functional polymorphisms in
      serotonin and dopamine-related genes and pain modulation. Two paradigms of pain
      modulation were administered to 191 healthy participants in a random order:
      Conditioned Pain Modulation in response to painful stimuli (CPM(painful)) tested
      by the coadministration of repeated short painful heat stimuli and a conditioning
      tonic cold pain stimulation; and Conditioned Pain Modulation in response to
      nonpainful stimuli (CPM(nonpainful)) tested similarly, except for using a
      painless conditioning stimulation. Using the Transmission Disequilibrium Test
      (TDT), functional variable number of tandem repeat (VNTR) polymorphisms of the
      following candidate genes were studied: 1) serotonin transporter (5-HTTLPR); 2)
      dopamine transporter (DAT1); 3) dopamine receptor 4 (DRD4); and 4) monoamine
      oxidase A (MAOA). DNA samples from both participants and their parents were
      analyzed. A significant association was found between CPM(nonpainful) and the 5
      HTTLPR polymorphism (P = .001). More specifically, carriers of the long allele
      exhibited a significantly higher magnitude of CPM(nonpainful) than carriers of
      the short allele. No associations were found between the dopamine-related genes
      and both types of pain modulation. These results highlight the importance of
      serotonin in endogenous analgesia. PERSPECTIVE: This article presents an
      association between the serotonin transporter gene polymorphism (5-HTTLPR) and
      pain modulation derived by nonpainful conditioned pain modulation
      (CPM(nonpainful)), rather than painful conditioned pain modulation
      (CPM(painful)). These findings emphasize the complex role of serotonin in pain
      modulation, and highlight the importance of genetic studies in the understanding
      of interindividual differences in sensitivity to pain.

PMID- 21719352
TI  - Involvement of NGF in the rat model of persistent muscle pain associated with
      taut band.
AB  - Myofascial pain syndrome (MPS) is an important clinical condition characterized
      by chronic muscle pain and a myofascial trigger point (MTrP) located in a taut
      band (TB). However, its pathogenic mechanism is still unclear. We developed an
      animal model relevant to conditions of MPS, and analyzed the mechanism of the
      muscle pain in this model. We applied eccentric contraction (EC) to a rat's
      gastrocnemius muscle (GM) for 2 weeks, and examined the mechanical withdrawal
      thresholds, histological changes, and expressions and contents of nerve growth
      factor (NGF). The mechanical withdrawal threshold decreased significantly at the
      next day of first EC and continued up to 9 days after EC. TBs were palpable at 3
      to 8 days after initiation of EC. In EC animals, necrotic and regenerating muscle
      cells were found significantly more than in control animals. In EC animals, NGF
      expressions in regenerating muscle cells and NGF contents of GM were
      significantly higher than control animals. Administration of NGF receptor (TrkA)
      inhibitor K252a showed significant suppression of mechanical hyperalgesia in EC
      animals. Repeated EC induced persistent mechanical muscle hyperalgesia associated
      with TB. NGF expressed in regenerating muscle cells may have an important role in
      persistent mechanical muscle hyperalgesia which might be relevant to pathogenesis
      of MPS. PERSPECTIVE: The present study shows that NGF expressed in regenerating
      muscle cells is involved in persistent muscular mechanical hyperalgesia. NGF-TrkA
      signaling in primary muscle afferent neurons may be one of the most important and
      promising targets for MPS.

PMID- 21719353
TI  - Postoperative lymphocele after revision circumferential long-segment scoliosis
      construct for pseudarthrosis.

PMID- 21719354
TI  - Professional component payment reductions for diagnostic imaging examinations
      when more than one service is rendered by the same provider in the same session:
      an analysis of relevant payment policy.
AB  - PURPOSE: The aim of this study was to assess potential physician work
      efficiencies when more than one diagnostic imaging study is interpreted by the
      same provider during the same session. METHODS: Medicare Physician Fee Schedule
      data from the American Medical Association Resource-Based Relative Value Scale
      Data Manager for 2011 were analyzed to quantify relative contributions of
      preservice, intraservice, and postservice physician work to the total work of
      rendering diagnostic imaging services. An expert panel review identified
      potential duplications in preservice and postservice work when multiple
      examinations are performed on the same patient during the same session. Maximum
      potential percentage work duplication for various diagnostic imaging modalities
      was calculated and compared to US Government Accountability Office estimates.
      RESULTS: The relative contributions of preservice and postservice work to total
      work varied by modality, ranging from 20% [computed tomography (CT)] to 33%
      (ultrasound). The maximum percentage of potentially duplicated preservice and
      postservice activity ranged from 19% (nuclear medicine) to 24% (ultrasound).
      Maximum mean potentially duplicated work relative value units ranged from 0.0212
      for radiography to 0.0953 for magnetic resonance imaging (MRI). Maximum
      percentage work reduction ranged from 4.32% for CT to 8.15% for ultrasound. This
      corresponds to maximum professional Physician Fee Schedule reductions of only
      2.96% (CT) to 5.45% (ultrasound), approximating an order of magnitude less than
      the Government Accountability Office's recommendations. CONCLUSION: Although
      potential efficiencies in physician work occur when multiple services are
      provided to the same patient during the same session, these are highly variable
      and considerably less than previously estimated.

PMID- 21719355
TI  - Three techniques to laparoscopically improve restriction after failed gastric
      bypass: revision of failed LRYGB restriction.

PMID- 21719356
TI  - Jejunocolic fistula after Roux-en-Y gastric bypass.

PMID- 21719357
TI  - Optimizing long-term weight control after bariatric surgery: a pilot study.
AB  - BACKGROUND: Although bariatric surgery is associated with significant overall
      weight loss, many patients experience suboptimal outcomes. Our objective was to
      document the preliminary efficacy of a behavioral intervention for bariatric
      surgery patients with relatively poor long-term weight loss and to explore the
      factors related to outcome at an academic medical center in the United States.
      METHODS: Patients with a body mass index (BMI) >= 30 kg/m(2) who had undergone
      bariatric surgery >= 3 years before study entry and had <50% excess weight loss
      were enrolled. The participants were randomly assigned to a 6-month behavioral
      intervention or wait list control group. The assessments were conducted at
      baseline (before intervention) and 6 months (after intervention) and 12 months (6
      mo follow-up). RESULTS: On average, the participants (n = 36) had undergone
      surgery 6.6 years before study entry. The average age was 52.5 +/- 7.1 years, and
      the BMI was 43.1 +/- 6.2 kg/m(2); most participants were women (75%) and white
      (88.9%). The intervention patients had a greater percentage of excess weight loss
      than did the wait list control group at 6 (6.6% +/- 3.4% versus 1.6% +/- 3.1%)
      and 12 (5.8% +/- 3.5% versus .9% +/- 3.2%) months. However, the differences were
      not significant and the results varied. The intervention patients with more
      depressive symptoms (P = .005) and less weight regain before study entry (P =
      .05) experienced a greater percentage of excess weight loss. CONCLUSION:
      Behavioral intervention holds promise in optimizing long-term weight control
      after bariatric surgery. More research is needed on when to initiate the
      intervention and to identify which patients will benefit from this type of
      approach.

PMID- 21719358
TI  - Predictors of pulmonary complications after bariatric surgery.
AB  - BACKGROUND: Postoperative pneumonia (PP) and respiratory failure (PRF) are known
      to be the most common nonwound complications after bariatric surgery. Our
      objective was to identify their current prevalence after bariatric surgery and to
      study the preoperative factors associated with them using data from the American
      College of Surgeons' National Surgical Quality Improvement Program. METHODS:
      Patients undergoing bariatric surgery were identified from the National Surgical
      Quality Improvement Program (2006-2008), a multicenter, prospective database.
      Univariate analysis and multivariate logistic regression analysis were performed.
      RESULTS: Of 32,889 patients, PP was diagnosed in 187 patients (.6%) and PRF in
      204 patients (.6%). The overall 30-day morbidity rate was 6.4%, with PP and PRF
      accounting for 18.7%. The 30-day mortality rate was greater for the patients with
      PP and PRF than those without (4.3% versus .16% and 13.7% versus .10%, P <
      .0001). The hospital length of stay was also longer in patients with PP/PRF (P <
      .0001). On multivariate analysis, congestive heart failure (odds ratio 5.3, 95%
      confidence interval 1.20-23.26) and stroke (odds ratio 4.1, 95% confidence
      interval 1.42-11.49) were the greatest preoperative risk factors for PP. Previous
      percutaneous coronary intervention (odds ratio 2.8, 95% confidence interval 1.64
      4.74) and dyspnea at rest (odds ratio 2.64, 95% confidence interval 1.13-6.13)
      were the factors most strongly associated with PRF. Bleeding disorder, age,
      chronic obstructive pulmonary disease, and type of surgery were risk factors for
      both (P < .05). Smoking also predisposed to PP, and diabetes mellitus, anesthesia
      time, and increasing weight also predisposed to PRF (P < .05 for all).
      CONCLUSION: Although PP and PRF are infrequent, they account for one fifth of the
      postoperative morbidity and are associated with significantly increased 30-day
      mortality. They can be predicted by various risk factors, emphasizing the
      importance of patient optimization and careful selection before bariatric
      surgery.

PMID- 21719359
TI  - Long-term follow-up after laparoscopic management of endometrial cancer in the
      obese: a fifteen-year cohort study.
AB  - STUDY OBJECTIVE: To assess the surgical outcomes and long-term results of
      laparoscopic treatment of endometrial cancer in obese patients, and compare these
      results with those of nonobese women. DESIGN: Retrospective cohort study
      (Canadian Task Force classification II-2). SETTING: Two referral cancer centers.
      PATIENTS: Fifty-two obese and 155 nonobese women with clinical stage I
      endometrial cancer managed by laparoscopy from 1990-2005 in two referral centers.
      INTERVENTIONS: Demographic, surgical, perioperative and pathological
      characteristics of obese women and nonobese women with endometrial cancer treated
      by laparoscopy were analyzed and then compared. Recurrence-free and overall
      survival was calculated by use of Kaplan-Meier method. MEASUREMENTS AND MAIN
      RESULTS: Median BMI of the study population was 26.2 Kg/m(2). Median BMI among
      obese patients was 34.2 Kg/m(2). The conversion rate was independent from the BMI
      of the patient (3.8% vs 4.5%, p = .80). Neither mean operative time (187.5 vs 172
      min, p = .11) neither hospital stay (5.2 vs 4.9 days, p = .44) were related with
      BMI. Lymphadenectomy was considered not feasible in 7 obese (17%) and 8 nonobese
      (7%) women (p = 0.09). Fewer lymph nodes were retrieved among obese women (8
      versus 11, p <.0002). No differences were found between the groups in terms of
      perioperative complications. Median follow-up was 69 and 71 months for the obese
      and nonobese, respectively (p = .59). Overall and disease-free 5-year survival
      rates did not differ between obese and nonobese patients (90.3% and 87.5% versus
      88.5% and 89.8%, respectively). CONCLUSION: Despite some limitations, the
      laparoscopic approach seems to be particularly useful for obese patients with
      endometrial cancer, with similar survival and recurrence rates and without any
      more complications compared to the nonobese population.

PMID- 21719360
TI  - Nanosecond pulsed electric field induced cytoskeleton, nuclear membrane and
      telomere damage adversely impact cell survival.
AB  - We investigated the effects of nanosecond pulsed electric fields (nsPEF) on three
      human cell lines and demonstrated cell shrinkage, breakdown of the cytoskeleton,
      nuclear membrane and chromosomal telomere damage. There was a differential
      response between cell types coinciding with cell survival. Jurkat cells showed
      cytoskeleton, nuclear membrane and telomere damage that severely impacted cell
      survival compared to two adherent cell lines. Interestingly, disruption of the
      actin cytoskeleton in adherent cells prior to nsPEF exposure significantly
      reduced cell survival. We conclude that nsPEF applications are able to induce
      damage to the cytoskeleton and nuclear membrane. Telomere sequences, regions that
      tether and stabilize DNA to the nuclear membrane, are severely compromised as
      measured by a pan-telomere probe. Internal pore formation following nsPEF
      applications has been described as a factor in induced cell death. Here we
      suggest that nsPEF induced physical changes to the cell in addition to pore
      formation need to be considered as an alternative method of cell death. We
      suggest nsPEF electrochemical induced depolymerization of actin filaments may
      account for cytoskeleton and nuclear membrane anomalies leading to sensitization.

PMID- 21719361
TI  - Bordetella species in children with cystic fibrosis: what do we know? The role in
      acute exacerbations and chronic course.
AB  - Despite vaccination, pertussis is still endemic in the Netherlands. A literature
      search was performed to verify what is known about the role of Bordetella species
      in children with cystic fibrosis, with regard to the incidence of Bordetella
      infections, the involvement in pulmonary exacerbations and the influence on
      chronic course. Little is known about the frequency of Bordetella infections and
      the involvement of Bordetella species both in relation to the chronic course of
      cystic fibrosis and to pulmonary exacerbations. Since it is difficult to detect
      Bordetella species in cultures and few sputum cultures investigated have been
      obtained during an exacerbation, it is likely that the frequency of Bordetella
      species in CF patients is underestimated. Identification of Bordetella species in
      these patients may have serious consequences for the treatment of exacerbations
      in CF. Future research investigating the role of Bordetella species in cystic
      fibrosis should use specific techniques to detect Bordetella in cultures.

PMID- 21719362
TI  - Review: Staphylococcus aureus and MRSA in cystic fibrosis.
AB  - BACKGROUND: Staphylococcus aureus (S. aureus) is one of the earliest bacteria
      detected in infants and children with cystic fibrosis (CF). The rise of
      methicillin resistant S. aureus (MRSA) in the last 10 years has caused a lot of
      attention to this organism. RESULTS: The aim of this review is to provide a
      general overview of methicillin sensitive S. aureus (MSSA) and MRSA, discuss
      special aspects of S. aureus in cystic fibrosis, and to review treatment
      concepts. Microbiology of the organism will be reviewed along with data regarding
      the epidemiology of both MSSA and MRSA. Antibiotic treatments both in regards to
      acute management and eradication of MSSA and MRSA will be reviewed. Prophylaxis
      of MSSA in CF remains controversial. Treatment with anti-staphylococcal agents
      reduces the infection rate with MSSA but may lead to a higher rate of infection
      with P. aeruginosa. In regards to MRSA, there is a paucity of clinical data
      regarding approaches to eradication. CONCLUSIONS: To advance the care of CF
      patients, controlled clinical trials are urgently needed to find the optimal
      approach to treating CF patients who are infected with either MSSA or MRSA.

PMID- 21719363
TI  - A simple HPLC method for plasma level monitoring of mitotane and its two main
      metabolites in adrenocortical cancer patients.
AB  - Mitotane (o,p'-DDD or (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane,
      DDD) is the drug of choice for non-resectable and metastatic adrenocortical
      carcinomas (ACC). Measurement of mitotane and metabolites, o,p'-DDE (1,1-dichloro
      2-[p-chlorophenyl]-2-[o-chlorophenyl]ethene, DDE) and o,p'-DDA (1,1-[o,p'
      dichlorodiphenyl] acetic acid, DDA) provides a better understanding of mitotane
      pharmacokinetics and pharmacodynamics. We have developed a simple, robust and
      efficient high performance liquid chromatography (HPLC) method to measure
      mitotane and its two main metabolites, DDE and DDA. The method involves a single
      ethanol extraction of mitotane, DDE, DDA, and an internal standard (int std) p,p'
      DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane) with an extraction efficiency of
      77-88%. All compounds are measured simultaneously using a reversed-phase phenyl
      HPLC column with an isocratic elution of mobile phase at a flow rate of 0.6
      ml/min followed by UV detection at lambda 226 nm. Inter and intra-day validation
      demonstrates good reproducibility and accuracy. Limits of quantitation are 0.2
      MUg/ml for mitotane and DDE, and 0.5 MUg/ml for DDA. The method has been
      evaluated in plasma from 23 patients on mitotane therapy, revealing DDA
      concentrations 1-18 times higher than the parent compound.

PMID- 21719364
TI  - [Cost-effectiveness of exenatide versus insulin glargine in Spanish patients with
      obesity and type 2 diabetes mellitus].
AB  - BACKGROUND AND OBJECTIVES: Exenatide, a GLP-1 receptor agonist for adjuvant
      treatment of type 2 diabetes mellitus (T2DM), has been shown to be as effective
      as insulin glargine (IG) for reducing glycated hemoglobin levels combined with
      metformin or/and sulphonylureas. Exenatide is associated to weight reduction and
      a higher incidence of gastrointestinal adverse events. The objective of this
      study was to assess the cost-effectiveness of exenatide as compared to IG in
      obese patients with T2DM not achieving an adequate blood glucose control from the
      perspective of the Spanish healthcare system. METHODS: Pharmacoeconomic model
      inputs were obtained from an obese subpopulation (BMI >= 30 k/m(2)) of an
      international, randomized, controlled clinical trial comparing exenatide with IG
      in poorly controlled T2DM patients, and were supplemented with country-specific
      data. RESULTS: Exenatide was associated to improvements in life-years gained and
      quality-adjusted life years (QALYs) by 0.11 and 0.62 respectively versus IG.
      Direct costs were ? 9,306 higher as compared to IG (? 47,010 versus ? 37,704,
      with increased pharmacy costs as the main driver). Exenatideis incremental cost
      effectiveness ratio was ? 15,068 per QALY gained versus IG. CONCLUSIONS:
      Exenatide was associated to greater clinical benefits and higher costs in obese
      T2DM patients as compared to IG. Considering a willingness-to-pay threshold of ?
      30,000 per QALY gained in the Spanish setting, exenatide represents an efficient
      option in comparison with IG.

PMID- 21719365
TI  - The continent ileostomy: an alternative to end ileostomy? Short and long-term
      results of a single institution series.
AB  - INTRODUCTION: Total proctocolectomy, ensuring eradication of all diseased
      colorectal mucosa is the treatment of choice for ulcerative colitis, familial
      adenomatous polyposis. Before the era of ileal pouch anal anastomosis, definitive
      ileostomy was required. The aim of this study is to define both early and late
      morbidity and the functional result of continent ileostomy. METHODS: All
      patients' chart who had a continent ileostomy in our department were reviewed.
      The functional result was evaluated in 43 patients. RESULTS: Forty-nine patients
      (34 women) with a mean age of 42 years (range: 17-69) underwent a continent
      ileostomy, 32 following a restorative proctocolectomy. The mean follow-up was
      20.5 (range: 3-34) years. Seventeen patients (35%) experienced an early
      postoperative complication requiring reintervention in two patients. There was no
      mortality, and conversion to an end ileostomy was not required. Twenty-two
      patients developed late complications requiring 50 reoperations. The mean number
      of catheterisations per 24h was 4.4. The SF36 questionnaire showed values close
      to those of the general population. CONCLUSION: Continent ileostomy carries a
      significant risk of non-severe complications. In selected patients, it represents
      a valuable alternative to an end ileostomy, in particular when restorative
      proctocolectomy has failed.

PMID- 21719366
TI  - Surgical decision criteria: Bednar tumour of the foot in a child.
AB  - An 8-year-old boy was admitted for excision of a putative 'blue nevus' on the
      left foot. Histological examination and immunohistochemistry revealed a Bednar
      tumour, the pigmented variant of dermatofibrosarcoma protuberans. Surgical
      options considered by a multidisciplinary team included wide local excision, Mohs
      micrographic surgery or a staged excision with examination of several
      histological sections. The third alternative procedure was chosen after
      consideration of tumour and patient factors to achieve the best possible
      clinical, cosmetic and functional outcome. After the final surgical procedure
      with resection of the third metatarsal bone, all peripheral margins were free of
      tumour, and the interdigital space was reconstructed with a pedicled pulpa flap.
      Three years after surgery, there was no tumour recurrence, and further long-term
      follow-up for this patient will be provided.

PMID- 21719367
TI  - Dermoscopy--time for plastic surgeons to embrace a new diagnostic tool?

PMID- 21719368
TI  - Modified resection technique for proximal fibular osteochondromas.
AB  - Osteochondroma is one of the most common tumors arising from the proximal fibula.
      Surgical treatment of proximal fibula osteochondromas may vary from debulking to
      resection of proximal fibula. We describe a modified surgical technique for
      excision of proximal fibular osteochondromas which preserves the proximal tibio
      fibular joint (PTFJ). We present a series of six cases of symptomatic proximal
      fibular osteochondroma. Four cases were solitary osteochondromas while two were a
      manifestation of a hereditary multiple exostoses. Indication for surgery was
      peroneal nerve symptoms in three, cosmesis in one, restricted knee motion in one,
      and pain in one case. All these cases were operated by a modified resection
      technique where the head of fibula was preserved. The PTFJ was preserved. Lateral
      stabilizing structures of the knee were left undisturbed, and hence did not need
      repair. Complications occurred in two patients, one had marginal wound necrosis
      and one had persistent weakness of extensor haullicis longus. At a minimum follow
      up of 2 years, none had recurrence or late disruption of PTFJ.

PMID- 21719369
TI  - Left pancreatectomy with splencectomy by the anterograde approach for
      adenocarcinoma of the pancreas.

PMID- 21719370
TI  - Treatment of hypertension in the emergency department.
AB  - This review updates concepts of hypertension evaluation and management in
      patients presenting to the emergency department. It outlines the current
      challenges faced by emergency physicians in the identification and management of
      hypertensive patients: In spite of published emergency care guidelines,
      identification and referral rates remain low in patients presenting to the
      emergency department with moderate blood pressure (BP) elevations. In patients
      with severely elevated BP, the evaluation for acute end organ damage remains
      inconsistent and is symptom-based. Using current consensus guidelines, this
      review provides an algorithm for the management of the hypertensive emergency
      department patient. The final section of this review outlines management
      strategies for specific hypertensive emergencies.

PMID- 21719371
TI  - Vascular and cardiac functional and structural screening to identify risk of
      future morbid events: preliminary observations.
AB  - Risk factors have served to identify patients in need of antihypertensive and
      lipid-lowering therapy. Because of their limited sensitivity and specificity, we
      developed a screening program using noninvasive testing and a scoring system
      aimed at detecting functional and structural cardiovascular abnormalities in
      asymptomatic individuals. Ten cardiovascular tests were performed in 1 hour by a
      single technologist. Tests were scored as normal (0), borderline abnormal (1), or
      abnormal (2). Total disease score (DS) could range from 0 (all tests normal) to
      20 (all tests abnormal). Scores of 0-2 were classified as normal, 3-5 as early
      disease, and 6+ as advanced disease. Morbid events during follow-up of 6 months
      to 8 years were determined from mailed questionnaires. Framingham risk scores
      (FRS) were calculated using published algorithms. Thirty-five morbid events (1 of
      169 in the "normal" group, 8 of 214 in the "early disease" group, and 26 of 230
      in the "advanced disease" group) occurred during the follow-up period among the
      613 individuals who completed the questionnaire. Risk for morbid events was
      highly significantly different between the Kaplan-Meier curves based on disease
      detection (log rank 21.75, P <= .0001). FRS were significantly different but less
      discriminating, with five morbid events in the 227 subjects with FRS <10, eight
      in 162 with FRS 10-13, and 22 of 227 with FRS >13 (log rank 9.80, P = .0074). The
      area under receiver operating characteristic curve for DS (0.74) surpassed that
      of FRS (0.66) and was not improved when both were included in the model. Neither
      blood pressure levels nor low-density lipoprotein cholesterol levels provided
      adequate discrimination. Identifying early disease in asymptomatic individuals
      provides a better guide to the need for preventive therapy than traditional risk
      factor assessment.

PMID- 21719372
TI  - Traffic air pollution and other risk factors for respiratory illness in
      schoolchildren in the niger-delta region of Nigeria.
AB  - BACKGROUND: Association of childhood respiratory illness with traffic air
      pollution has been investigated largely in developed but not in developing
      countries, where pollution levels are often very high. OBJECTIVES: In this study
      we investigated associations between respiratory health and outdoor and indoor
      air pollution in schoolchildren 7-14 years of age in low socioeconomic status
      areas in the Niger Delta. METHODS: A cross-sectional survey was carried out among
      1,397 schoolchildren. Exposure to home outdoor and indoor air pollution was
      assessed by self-report questionnaire. School air pollution exposures were
      assessed using traffic counts, distance of schools to major streets, and
      particulate matter and carbon monoxide measurements, combined using principal
      components analysis. Hierarchical logistic regression was used to examine
      associations with reported respiratory health, adjusting for potential
      confounders. RESULTS: Traffic disturbance at home (i.e., traffic noise and/or
      fumes evident inside the home vs. none) was associated with wheeze [odds ratio
      (OR) = 2.16; 95% confidence interval (CI), 1.28-3.64], night cough (OR = 1.37;
      95% CI, 1.03-1.82), phlegm (OR = 1.49; 95% CI, 1.09-2.04), and nose symptoms (OR
      = 1.40; 95% CI, 1.03-1.90), whereas school exposure to a component variable
      indicating exposure to fine particles was associated with increased phlegm (OR =
      1.38; 95% CI, 1.09-1.75). Nonsignificant positive associations were found between
      cooking with wood/coal (OR = 2.99; 95% CI, 0.88-10.18) or kerosene (OR = 2.83;
      95% CI, 0.85-9.44) and phlegm compared with cooking with gas. CONCLUSION: Traffic
      pollution is associated with respiratory symptoms in schoolchildren in a deprived
      area of western Africa. Associations may have been underestimated because of
      nondifferential misclassification resulting from limitations in exposure
      measurement.

PMID- 21719374
TI  - Particulate matter-induced health effects: who is susceptible?

PMID- 21719373
TI  - Thyroid dysfunction as a mediator of organochlorine neurotoxicity in preschool
      children.
AB  - BACKGROUND: Exposure to organochlorine compounds (OCs) can alter thyroid function
      in humans, and hypothyroidism during early life can adversely affect a child's
      neurodevelopment. OBJECTIVES: In this study we aimed to assess the relationship
      between developmental organochlorine exposures and thyroid function and the
      relationship between thyroid function and subsequent neurodevelopment. METHODS: A
      population-based birth cohort of 182 children was followed annually up to 5.5
      years of age. The assessments included OC concentrations in maternal pregnancy
      serum and milk, clinical thyroid parameters in maternal and cord serum, and
      subsequent neuropsychological outcomes of the child, along with sociodemographic
      cofactors. Resin triiodothyronine uptake ratio (T3RU) was also assessed as an
      estimate of the amount of thyroxine-binding globulin (TBG) sites unsaturated by
      thyroxine. The T3RU is high in hyperthyroidism and low in hypothyroidism.
      RESULTS: The findings showed consistent inverse and monotonic associations
      between organochlorine exposure and T3RU after covariate adjustments. We observed
      no associations with other thyroid parameters. T3RU was positively associated
      with improved performance on most of the neuropsychological tests. For other
      thyroid parameters, the findings were less consistent. CONCLUSIONS: The results
      suggest that OC exposures may decrease the T3RU during early life, which is a
      proxy measure of the binding capacity of TBG. In addition, minor decreases of the
      thyroid function may be inversely associated with a child's neurodevelopment.

PMID- 21719376
TI  - Methane found in well water near fracking sites.

PMID- 21719377
TI  - Global prevention of environmental and occupational cancer.

PMID- 21719379
TI  - Phosphorus recovery: new approaches to extending the life cycle.

PMID- 21719380
TI  - Can cigarette alternatives deliver a safer fix?

PMID- 21719381
TI  - ADHD, lead, and PCBs: appropriate comparison studies.

PMID- 21719382
TI  - Thyroid cancer after Chornobyl: increased risk persists two decades after
      radioiodine exposure.

PMID- 21719383
TI  - Environmental health research implications of methylmercury.

PMID- 21719384
TI  - Plastics and food sources: dietary intervention to reduce BPA and DEHP.

PMID- 21719385
TI  - Gate wait for better air.

PMID- 21719387
TI  - A shift in policy? Learning from China's environmental challenges and successes.

PMID- 21719388
TI  - Chemical aftermath: contamination and cleanup following the Tohoku earthquake and
      tsunami.

PMID- 21719389
TI  - Home energy-efficiency retrofits.

PMID- 21719391
TI  - PCBs may impede IVF success: failed embryo implantation linked to exposure.

PMID- 21719392
TI  - Treatment of HIV-related primary central nervous system lymphoma with AZT high
      dose, HAART, interleukin-2 and foscarnet in three patients.
AB  - PURPOSE: Combined immunomodulatory and antiviral treatment was administered to
      three patients with newly diagnosed HIV-associated primary central nervous system
      lymphoma (PCNSL) in an attempt to improve outcomes. PATIENTS AND METHODS: Three
      patients from our institution who were recently diagnosed with HIV-associated
      PCNSL received intravenous azidothymidine (AZT) 1.6 gr. bid for two weeks,
      followed by oral AZT 250mg bid from day 15. In addition, complementary highly
      active antiretroviral therapy (HAART) with a second nucleoside reverse
      transcriptase inhibitor (NRTI) plus one protease inhibitor (PI) and interleukin 2
      (IL-2) subcutaneously 2 million units twice daily (bid) plus foscarnet 90mg/kg
      bid were administered on days 1-14. One patient received anti-Epstein-Barr virus
      (EBV)-maintenance therapy with ganciclovir, followed by cidofovir. RESULTS: All
      patients experienced progressive disease while on induction therapy, and switched
      early to whole-brain radiation therapy (WBRT) as second line-treatment. No grade
      3 or 4 toxicities were observed. Two patients died on days 50 and 166
      respectively due to progressive disease. The third patient with histo?logically
      proven lymphoproliferation and only suspected PCNSL remained alive at 53 months.
      He was on HAART and remained clinically and neurologically stable. CONCLUSION:
      Although IL-2, HAART, high-dose AZT and foscarnet are used for other HIV-related
      conditions, they did not demonstrate benefit in lymphoma remission for 2 HIV-
      associated PCNSL patients. The third patient went into delayed remission after
      additional radiotherapy and was in good clinical and neurological health status
      over 53 months after diagnosis.

PMID- 21719393
TI  - Activity and side effects of imatinib in patients with gastrointestinal stromal
      tumors: data from a German multicenter trial.
AB  - Gastrointestinal stromal tumors (GIST) are mesenchymal tumors that in the past
      were classified as leiomyosarcomas or leiomyomas not responding to standard
      sarcoma chemotherapy. In several phase I and II trials the efficacy and safety of
      imatinib was shown before the largest trial ever performed in a single sarcoma
      entity revealed response rates (CR/PR) of 52 %. This multicenter phase II trial
      presented here was performed to open access to imatinib for patients with
      unresectable or metastastatic GIST when the EORTC 62005 trial had been closed
      before imatinib was approved in Germany. It was designed to follow the best
      clinical response and to assess the efficacy, safety and tolerability of imatinib
      400mg/d in patients with unresectable or metastatic gastrointestinal stromal
      tumor. - 95 patients were treated in this trial with Imatinib 400mg/d. Four
      patients (4.6 %) attained a complete response and 26 patients (29.9%) a partial
      response to imatinib treatment. Forty-one patients (47.1 %) revealed a stable
      disease and 16 patients (18.4 %) had a progressive disease. - Of the progressive
      patients 22% showed a partial response and 67 % showed stable disease after
      escalating the dose to 800 mg. According to SWOG tumor response classification,
      66 patients (70%) were free of progression within the first year of treatment. -
      Seventy-one patients (74.7%) experienced adverse events or severe adverse events
      with a suspected relationship to the study drug. Among these, the most common
      were nausea (n=27 patients, 28.4 %), eyelid edema and peripheral edema in 23
      patients each (24.2 %), diarrhea in 20 patients (21.1 %), muscle cramps in 15
      patients (15.8 %) and fatigue in 13 patients (13.7 %). - Imatinib 400 mg/d led to
      disease stabilisation in 81,6% of patients with unresectable or metastatic
      malignant GIST. Thirty-four percent of patients attained a tumor remission
      (partial or complete response). The safety profile of imatinib based on adverse
      event assessment is favorable. Imatinib is generally well tolerated in patients
      with gastrointestinal stromal tumors.

PMID- 21719394
TI  - Intrahepatic type II gall bladder perforation by a gall stone in a CAPD patient.
AB  - INTRODUCTION: Perforation of the gall bladder represents a rare, but life
      threatening complication of cholecystitis. Clinical presentation may vary between
      severe peritonism in acute perforation and absence of symptoms in subacute or
      chronic progression of perforation. Abdominal imaging like ultrasound or CT-scan
      are important tools for immediate diagnose of gall bladder perforation. CASE
      PRESENTATION: We report a case of a 30-year old female patient with end-stage
      kidney disease treated by continuous ambulatory peritoneal dialysis (CAPD) who
      was admitted to the emergency room with fever and mild abdominal pain. A type II
      gall bladder perforation by a solitary gall stone with development of a liver
      abscess was detected by abdominal ultrasound. CONCLUSION: Gall bladder
      perforations are rare but have to be considered in patients with abdominal pain
      and fever. Abdominal ultrasound is a reliable tool to establish diagnosis.

PMID- 21719395
TI  - Surgical hip dislocation in symptomatic cam femoroacetabular impingement: what
      matters in early good results?
AB  - In order to assess outcome and possible predictors of early good results, a
      prospective study on 22 patients who were treated with save surgical hip
      dislocation for symptomatic isolated cam-type femoroacetabular impingement (FAI)
      was performed. After a follow-up of 6 and 12 months, standard clinical and
      radiographic parameters were recorded. A statistically significant improvement of
      the clinical status according to the Harris hip score could be assessed at six
      months (p-value = 0.003) and 12 months (p-value = 0.001) post-surgery. By
      comparing standard clinical and radiographic preoperative parameters with various
      follow-up outcomes, we revealed no specific parameter with predictive value.
      These findings are important for centers that have just started to use this
      surgical technique and are still identifying their learning curve.

PMID- 21719396
TI  - Respiratory symptoms in preterm infants: burden of disease in the first year of
      life.
AB  - OBJECTIVE: While respiratory symptoms in the first year of life are relatively
      well described for term infants, data for preterm infants are scarce. We aimed to
      describe the burden of respiratory disease in a group of preterm infants with and
      without bronchopulmonary dysplasia (BPD) and to assess the association of
      respiratory symptoms with perinatal, genetic and environmental risk factors.
      METHODS: Single centre birth cohort study: prospective recording of perinatal
      risk factors and retrospective assessment of respiratory symptoms during the
      first year of life by standardised questionnaires. MAIN OUTCOME MEASURES: Cough
      and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy
      (severe outcomes). PATIENTS: 126 preterms (median gestational age 28.7 weeks; 78
      with, 48 without BPD) hospitalised at the University Children's Hospital of Bern,
      Switzerland 1999-2006. RESULTS: Cough occurred in 80%, wheeze in 44%, re
      hospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the
      preterm infants. Using logistic regression, the main risk factor for common
      symptoms was frequent contact with other children. Severe outcomes were
      associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR-
      and CRIB-Score. CONCLUSIONS: Cough in preterm infants is as common as in term
      infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more
      often. Severe outcomes are associated with perinatal risk factors. Preterm
      infants who did not qualify for BPD according to latest guidelines also showed a
      significant burden of respiratory disease in the first year of life.

PMID- 21719397
TI  - Retrorectal tumours: literature review and vilnius university hospital
      "santariskiu klinikos" experience of 14 cases.
AB  - OBJECTIVE: Retrorectal tumours are rare lesions in adults. The diagnosis of
      retrorectal lesion is often difficult and misdiagnosis is common. We present
      significant number of cases in view of scarce information available on this
      matter. METHODS: 14 patients were treated at Vilnius university hospital
      "Santariskiu klinikos" Centre of abdominal surgery from 1997 to 2010. The case
      notes of patients who underwent surgery for a retrorectal tumour were reviewed
      retrospectively. Surgical histories, operations, histological tumour type,
      surgical time, weight of the specimen, blood loss, length of stay were analysed.
      RESULTS: 13 patients underwent laparotomy, 1 patient had combined perineal
      approach and laparotomy. The most common types of the tumour were fibroma (3
      cases), leiomyosarcoma (2 cases). 5 tumours (35,7%) were found to be malignant.
      57% of the patients had undergone at least one operation prior to definitive
      treatment. 5 female patients were initially admitted under gynaecologists.
      Hospital stay varied from 14 days to 22 days (mean 16.2 days). A report of a
      representative case is presented. CONCLUSIONS: Retrorectal lesions in female
      patients can mimic gynaecological pathology. Patients with this rare pathology
      are to be treated in a major tertiary hospital by surgeons, who are able to
      operate safely in the retrorectal space.

PMID- 21719398
TI  - Acute hepatitis C in persons infected with the human immunodeficiency virus
      (HIV): the "real-life setting" proves the concept.
AB  - OBJECTIVES: Outbreaks of sexually transmitted acute HCV infection have been
      described recently in several cities in the western world. The epidemic affects
      mainly MSM who are coinfected with HIV and is supposably linked to certain sexual
      risk practices. Here, we compared our findings with current knowledge and
      recommendations. METHODS: HIV-positive patients with the diagnosis of acute HCV
      infection were included in the retrospective analysis. The patients came from
      outpatient infectious disease centers in northern German cities. We looked at
      markers of HIV and HCV infection and compared patients who received treatment and
      those who did not. Treated patients were followed up to 72 weeks. RESULTS: Three
      hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C
      between 2001 and 2008 and were included in the analysis. All patients were male,
      315 (99%) patients were of caucasian origin, 296 (93%) declared homosexual
      contacts as a risk factor for HCV infection, intravenous drug use was declared in
      3 (1%) cases. Median age at HCV diagnosis was 40 years (range 20-69 years).
      Median HCV viral load was 1.2 x 106 IU/mL, 222 patients (70%) had HCV genotype 1,
      59 (18%) genotype 4. The median time of HIV infection was 5.5 years (range 0 to
      22.4 years). Median HIV viral load was 110 copies/mL (range 25 to 10x106
      copies/mL). The median CD 4 count was 461 cells/mm3 (range 55-1331 cells/mm3).
      Two hundred and fourty-six patients (77%) received anti-HCV treatment, and 175
      (55%) had completed therapy by the time of the analysis. Median treatment
      duration was 33 weeks (IQR 24.1-49.9). 93 of the 175 treated patients (53%)
      reached a sustained virological response (SVR). In the multivariate analysis, ART
      at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets
      were associated with SVR. Treatment duration was significantly higher in the SVR
      group (40.6 weeks vs 26.6 weeks, p<0.0001). Seventy-three patients (23%) did not
      receive anti-HCV treatment. In 19 of the untreated patients (26%) the hepatitis C
      virus was cleared spontaneously. CONCLUSIONS: Our findings confirm that acute
      hepatitis C in HIV infected patients affects mainly MSM who acquire HCV sexually.
      Patients had a short duration of HIV infection and a stable immunological
      situation. In this real-life setting from urban regions in northern Germany,
      treatment rates appear to be high and effective.

PMID- 21719399
TI  - Pityriasis lichenoides et varioliformis acuta exacerbated after tonsillectomy.

PMID- 21719400
TI  - Familial anetoderma: a report of two families.
AB  - Anetoderma is a rare cutaneous disorder where a localized dermal defect of
      elastic fibers determines depressed areas and often herniated saclike skin.
      Primary anetoderma is an idiopathic phenomenon while secondary anetoderma is
      related to various conditions. The term primary anetoderma implies that the
      lesions occur in clinically normal skin although they may be associated with
      another dermatological or systemic disease or condition, without a well
      established relationship. The term secondary anetoderma implies that anetoderma
      occurred on the same site as another skin lesion. Familial anetoderma is a very
      rare condition that can be associated with bony, neurological and ocular
      anomalies. Recently some families with familial anetoderma have been described,
      where the disease seems to be limited to the skin. The pathogenesis for familial
      anetoderma is still unclear. It has been reported in only 10 families and in the
      first 4 reported families, anetoderma was always associated with extra-cutaneous
      abnormalities, while in the remaining 6 families, all described in last three
      decades, anetoderma was limited to the skin. We report here another two families
      with anetoderma without any associated disease and we review the literature on
      familial anetoderma.

PMID- 21719401
TI  - Pityriasis rubra pilaris with prominent acantholytic dyskeratosis.

PMID- 21719402
TI  - A variant case of familial progressive hyperpigmentation.

PMID- 21719403
TI  - Cutis laxa: analysis of metalloproteinases and extracellular matrix expression by
      immunohistochemistry and histochemistry.
AB  - Upregulation of matrix metalloproteinases (MMPs) and downregulation of tissue
      inhibitors of metalloproteinases (TIMP) have been reported in cultured
      fibroblasts from patients with congenital cutis laxa (CL) or anetoderma. We
      determined the protein expressions of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1
      and collagen I, collagen III in vivo, to confirm their roles in the pathogenesis
      of cutis laxa. The protein expression of the MMPs and collagens from skin lesions
      of CL were detected by immunohistochemistry and analyzed by image analysis
      software. Markedly increased MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1
      associated with alteration of elastic and collagen fibers were found in two cases
      of CL, whereas increased MMP-3, MMP-9, MMP-12 accompanying a degradation of
      elastic fibers were detected in the third case. These results suggest an elevated
      expression of MMPs may play a role in the evolution or genesis of CL.

PMID- 21719404
TI  - Verrucous carcinoma arising in lichen simplex chronicus.

PMID- 21719405
TI  - Melanoma lymph node metastasis occurring simultaneously with multifocal
      sarcoidosis affecting lymph nodes and the lung: a diagnostic pitfall.

PMID- 21719406
TI  - Mast cells do not play a role in vitiligo.

PMID- 21719407
TI  - A photographic scale for the evaluation of facial skin aging in Indian women.
AB  - The process of facial skin aging differs between different ethnic populations.
      Standardized tools to objectively evaluate facial skin aging in clinical and
      epidemiological studies in different ethnic populations are needed. We designed
      and validated a photonumeric scale for assessment of facial aging in the Indian
      population. A total of 149 subjects were selected from an electronic photographic
      database of 300 women from the Mumbai region. An expert consensus panel selected
      nine subjects representing a spectrum of skin damage from none to severe, on the
      basis of wrinkling and tissue slackening. The nine-point scale, composed of one
      face-on and one oblique photo of the same subject per grade, was validated by
      nine independent judges in 99 subjects with a repetition two weeks later. Inter
      observer reliability and intra-observer reproducibility were calculated using
      Kappa coefficients. Validation of the scale showed a high level of inter-observer
      reliability between the consensus and independent panels, and intra-observer
      reproducibility between the two evaluations performed by the independent judges.
      In conclusion, this nine-point facial aging scale is a reliable tool for clinical
      evaluations of skin damage in Indian women, suitable for use in clinical and
      epidemiological studies.

PMID- 21719408
TI  - Lipomatous variant of eccrine angiomatous hamartoma.

PMID- 21719409
TI  - Camptodactyly: a 10-year series.
AB  - Camptodactyly is a non-traumatic, painless, non-neurogenic flexion deformity at
      the proximal interphalangeal joint of the little finger, which may occur in
      isolation or in various developmental dysmorphology syndromes. In a ten-year
      survey of almost 10,000 consecutive neurology outpatient referrals, using a
      passive case finding strategy, camptodactyly was observed with a frequency of
      0.43%. All were cases of isolated camptodactyly, and all but one were
      asymptomatic. Camptodactyly was more often bilateral, often asymmetric, than
      unilateral. A family history was common, sometimes with intrafamilial
      heterogeneity (symmetry, degree of angulation). The pattern of inheritance was
      not certain, but the predominance of female cases (both directly observed and
      reported in families) and a paucity of father-to-daughter cases suggested the
      possibility of either sex-linked dominant transmission or mitochondrial DNA point
      mutation. There was no evidence for aminoaciduria or taurinuria, as previously
      reported in some cases. Hence, camptodactyly is relatively common as an
      incidental finding in patients referred to general neurological outpatient
      clinics, and thus possibly also in the general population. It is possible that
      camptodactyly is a heterogeneous disorder. Further studies are required to
      ascertain whether this is the case, and to probe further the inheritance and
      pathogenesis of the disorder.

PMID- 21719410
TI  - 21st World Congress World Society of Cardio-Thoracic Surgeons. Abstracts.

PMID- 21719411
TI  - Effectiveness of E-self-help interventions for curbing adult problem drinking: a
      meta-analysis.
AB  - BACKGROUND: Self-help interventions without professional contact to curb adult
      problem drinking in the community are increasingly being delivered via the
      Internet. OBJECTIVE: The objective of this meta-analysis was to assess the
      overall effectiveness of these eHealth interventions. METHODS: In all, 9
      randomized controlled trials (RCTs), all from high-income countries, with 9
      comparison conditions and a total of 1553 participants, were identified, and
      their combined effectiveness in reducing alcohol consumption was evaluated by
      means of a meta-analysis. RESULTS: An overall medium effect size (g = 0.44, 95%
      CI 0.17-0.71, random effect model) was found for the 9 studies, all of which
      compared no-contact interventions to control conditions. The medium effect was
      maintained (g = 0.39; 95% CI 0.23-0.57, random effect model) after exclusion of
      two outliers. Type of control group, treatment location, type of analysis, and
      sample size did not have differential impacts on treatment outcome. A significant
      difference (P = .04) emerged between single-session personalized normative
      feedback interventions (g = 0.27, 95% CI 0.11-0.43) and more extended e- self
      help (g = 0.61, 95% CI 0.33-0.90). CONCLUSION: E-self-help interventions without
      professional contact are effective in curbing adult problem drinking in high
      income countries. In view of the easy scalability and low dissemination costs of
      such interventions, we recommend exploration of whether these could broaden the
      scope of effective public health interventions in low- and middle-income
      countries as well.

PMID- 21719412
TI  - Curbing alcohol use in male adults through computer generated personalized
      advice: randomized controlled trial.
AB  - BACKGROUND: In recent years, interventions that deliver online personalized
      feedback on alcohol use have been developed and appear to be a feasible way to
      curb heavy drinking. Randomized controlled trials (RCTs) among the general adult
      population, however, are scarce. The present study offers an RCT of Drinktest.nl,
      an online personalized feedback intervention in the Netherlands. OBJECTIVE: The
      aim of this study was to assess the effectiveness of computer-based personalized
      feedback on heavy alcohol use in male adults. METHODS: Randomization stratified
      by age and educational level was used to assign participants to either the
      intervention consisting of online personalized feedback or an information-only
      control condition. Participants were told as a cover story that they would
      evaluate newly developed health education materials. Participants were males (n =
      450), aged 18 to 65 years, presenting with either heavy alcohol use (> 20 units
      of alcohol weekly) and/or binge drinking (> 5 units of alcohol at a single
      occasion at least 1 day per week) in the past 6 months. They were selected with a
      screener from a sampling frame of 25,000 households. The primary outcome measure
      was the percentage of the participants that had successfully reduced their
      drinking levels to below the Dutch guideline threshold for at-risk drinking.
      RESULTS: Intention-to-treat analysis showed that in the experimental condition,
      42% (97/230) of the participants were successful in reducing their drinking
      levels to below the threshold at the 1-month follow-up as compared with 31%
      (67/220) in the control group (odds ratio [OR] = 1.7, number needed to treat
      [NNT] = 8.6), which was statistically significant (chi(2) (1) = 6.67, P = .01).
      At the 6-month follow-up, the success rates were 46% (105/230) and 37% (82/220)
      in the experimental and control conditions, respectively (OR = 1.4, NNT = 11.9),
      but no longer statistically significant (chi(2) (1) = 3.25, P = .07).
      CONCLUSIONS: Personalized online feedback on alcohol consumption appears to be an
      effective and easy way to change unhealthy drinking patterns in adult men, at
      least in the short-term.

PMID- 21719413
TI  - Cytotype distribution at a diploid-tetraploid contact zone in Chamerion
      (Epilobium) angustifolium (Onagraceae).
AB  - In North America, the geographic distributions of diploid and tetraploid
      Chamerion (formerly Epilobium) angustifolium overlap in a narrow zone along the
      southern border of the boreal forest and along the Rocky Mountains. We examined
      the frequency and distribution of diploid and tetraploid cytotypes in a narrow (5
      km) zone of sympatry across an elevational gradient and in putatively uniform
      diploid and tetraploid reference populations on the Beartooth Pass, in the Rocky
      Mountains of southern Montana-northern Wyoming. All five reference populations
      sampled were dominated by a single cytotype, but only one was completely uniform.
      In the zone of sympatry, 27 transects were sampled every 2 m for a total of 238
      plants. Reproductive status (vegetative, flower buds, open flowers) was recorded,
      and the ploidy of each plant was determined by flow cytometry. Diploid and
      tetraploid plants predominated (36 and 55%, respectively) but were
      heterogeneously distributed among the transects. Six of the 27 transects were
      fixed for a single cytotype (four transects, diploid; two transects, tetraploid),
      and in seven others either diploids or tetraploids predominated (frequency >75%).
      Triploids represented 9% of the total sample and occurred most frequently in
      transects containing both diploids and tetraploids (G = 3.4, df = 2, P = 0.07).
      Diploids were more often reproductive (in bud, flower, or fruit) than either
      triploids or tetraploids (G = 12.0, df = 2, P < 0.001) and were the only cytotype
      to have produced open flowers. These results suggest that the zone of sympatry is
      best characterized as a mosaic rather than a cline, with diploid and tetraploids
      in close proximity and that the distribution of polyploidy is regulated by
      ecological sorting in a heterogeneous physical environment.

PMID- 21719414
TI  - Galls on the marine red alga Prionitislanceolata (Halymeniaceae): specific
      induction and subsequentdevelopment of an algal-bacterial symbiosis.
AB  - Gall formation in Prionitis lanceolata is associated with aspecific eubacterium
      (Proteobacteria [alphasubclass], Rhodobacter grouping), which, typical
      ofbacterial symbionts, has not yet been cultivated or isolated in pureculture.
      This investigation tested the hypothesis that P.lanceolata gall formation was
      caused by the associated eubacteriumusing a species-specific rDNA probe (S-S
      P.l.sym-0949-a-A-25) toidentify and assay for symbiont presence during
      consecutive laboratoryinduction trials. Gall induction was quantified and whole
      cell in situhybridization used to determine the relative percentage of
      symbioticeubacteria in inoculation homogenates. In situ hybridization ofsymbionts
      in sections allowed localization and monitoring of thismicrobe during gall
      development. Induction trial results indicate asignificant correlation between
      bacterial symbiont presence and gallinitiation (P = 0.00005). The gall bacterium
      comprisedthe majority of the eubacteria hybridized in laboratory
      inductionhomogenates (85-97%), in galls induced in the laboratoryand in three
      algal populations in nature. The evidence presented heredemonstrates the
      causative role of the identified eubacterium in gallinduction and formation. This
      investigation is significant in theapplication of molecular methods towards
      understanding the roles ofnoncultivable marine bacteria in marine algal
      microbeinteractions.

PMID- 21719415
TI  - Interleukin-19: a new target to aim for?

PMID- 21719416
TI  - A common functional variant of endoplasmic reticulum aminopeptidase 2 (ERAP2)
      that reduces major histocompatibility complex class I expression is not
      associated with ankylosing spondylitis.

PMID- 21719417
TI  - Complete remission of myeloperoxidase-anti-neutrophil cytoplasmic antibody
      associated crescentic glomerulonephritis complicated with rheumatoid arthritis
      using a humanized anti-interleukin 6 receptor antibody.

PMID- 21719418
TI  - Does achieving clinical response prevent work stoppage or work absence among
      employed patients with early rheumatoid arthritis?
AB  - OBJECTIVES: To evaluate the impact of clinical response on work stoppage or work
      absence among employed people with early RA. METHODS: First-year data from the
      combination of MTX and etanercept trial was used. The analyses were restricted to
      the 205 patients working full or part time at baseline who answered questions on
      whether they stopped working or missed days from work in one or more of the four
      follow-up visits. Work stoppage referred to the first occurrence of subjects
      reporting stopping work. Work absence was defined as whether patients reported
      missed days from work. Clinical response and activity state considered included
      the ACR and European League against Rheumatism response criteria, 28-joint DAS
      (DAS-28) remission and the minimum clinically important difference of the HAQ
      score. RESULTS: After adjustment for baseline characteristics, ACR70 responders
      were 72% less likely to stop working and 55% less likely to miss work than ACR20
      non-responders (P < 0.05). Patients achieving DAS-28 remission were 54% less
      likely to stop work than those with DAS-28 > 3.2 (P < 0.05). Moderate
      improvements did not appear to effect work stoppage or missed days after
      adjustments. CONCLUSIONS: Results suggest that achieving clinical remission or
      major improvement might be necessary to significantly impact work outcomes.

PMID- 21719419
TI  - Methotrexate-associated lymphoproliferative disorder presenting as disseminated
      malignancy.

PMID- 21719420
TI  - Multi-examiner reliability of automated radio frequency-based ultrasound
      measurements of common carotid intima-media thickness in rheumatoid arthritis.
AB  - OBJECTIVES: To assess the reliability of the automated radio frequency (RF)-based
      US measurement of carotid intima-media thickness (IMT) performed by
      rheumatologists and to evaluate the variability between this method and the
      conventional B-mode US measurement of carotid IMT in RA patients. METHODS: Twelve
      rheumatologists measured in two blinded rounds the IMT of both common carotid
      arteries (CCAs) of seven RA patients with an automated RF-based method. At each
      round, a cardiologist measured both CCA-IMTs of the patients using an automated B
      mode method. Inter-observer reliability for RF-based IMT measurements was
      evaluated by the intra-class correlation coefficient (ICC). Intra-observer
      reliability for RF-based IMT measurements was assessed using the root mean square
      coefficient of variation (RMS-CV), Bland-Altman method and ICC. Agreement between
      the two US methods was evaluated by the Bland-Altman method, ICC and RMS-CV.
      RESULTS: Inter-observer ICCs for the RF-based CCA-IMT measurements were 0.85 (95%
      CI 0.69, 0.94) for the first round, and 0.77 (95% CI 0.55, 0.91) for the second
      round. RMS-CVs for the RF-based CCA-IMT measurements varied from 5.6 to 11.7%.
      The mean intra-observer ICC for the RF-based CCA-IMT measurements was 0.61 (95%
      CI 0.46, 0.71). In the Bland-Altman analysis for agreement between RF-based and B
      mode CCA-IMT measurements, the mean difference varied from -0.6 to -19.7 MUm.
      Inter-method ICCs varied from 0.57 to 0.83 for 11 rheumatologists. Inter-method
      RMS-CVs varied from 11.3 to 13.7%. CONCLUSIONS: Our results suggest that
      automated RF-based CCA-IMT measurement performed by rheumatologists can be a
      reliable method for assessing cardiovascular risk in RA patients.

PMID- 21719421
TI  - Thalidomide and dexamethasone followed by autologous stem cell transplantation
      for scleromyxoedema.

PMID- 21719422
TI  - Age, gender and disease-related platelet and neutrophil activation ex vivo in
      whole blood samples from patients with Behcet's disease.
AB  - OBJECTIVES: Behcet's disease (BD) is more severe among young males and disease
      severity decreases with age. Therefore, the effect of disease activity, gender
      and age on platelet and neutrophil activation in whole blood taken from patients
      with BD was investigated. METHODS: Using an anti-coagulant Tripotassium
      ethylenediaminetetra acetic acid (K3EDTA) plus citrate-theophylline-adenosine
      dipyridamole (CTAD) (K3EDTA/CTAD) that preserves the degree of platelet
      activation that exists in vivo, we assessed neutrophil and platelet activation,
      microparticles, and monocyte and neutrophil-platelet aggregate formation in 43 BD
      patients using flow cytometry. This is the first description of platelet
      activation and microparticles in BD patients using this methodology. RESULTS:
      Inactive [2.78 (0.56)%, P = 0.0009; 3.11 (0.78)%, P < 0.0001] and active [2.28
      (0.84)%, P < 0.0001; 3.071 (0.67)%, P = 0.0031] BD patients had significantly
      higher percentages of CD62P-expressing platelets and CD62P+ platelet
      microparticles as compared with healthy controls (HCs) [0.84 (0.1)% and 1.23
      (0.14)%], respectively. The percentages of CD62P+ platelets and CD62P+ platelet
      microparticles in female and male BD patients were also significantly higher than
      those expressed by female and male HCs. The percentages of CD62P+ microparticles
      were significantly increased in the 20-30-(P = 0.0301) and 31-50-(P < 0.0162)
      year age ranges, but not in the >50-year age group of BD patients. CONCLUSION: BD
      is a rare, chronic multi-systemic vasculitis and interaction of activated
      platelets with leucocytes has been linked to pathological disorders associated
      with vascular inflammation. Importantly, this study demonstrates that platelet
      microparticle activation is increased in BD. Also, this is the first report in
      which changes in platelet activation in BD are concordant with the observations
      that BD disease activity diminishes with age.

PMID- 21719423
TI  - Interleukin-19 blockade attenuates collagen-induced arthritis in rats.
AB  - OBJECTIVES: RA is the most common form of inflammatory arthritis. IL-19 acts as a
      pro-inflammatory cytokine involved in the pathogenesis of RA. We investigated
      whether anti-IL-19 antibody treatment would modulate the severity of the disease
      in a CIA rat model. METHODS: We generated a CIA model by immunizing rats with
      bovine type II collagen. CIA rats were s.c. treated with anti-IL-19 antibody
      1BB1. The effects of 1BB1 on CIA rats were determined by hind-paw thickness,
      severity score, bone destruction, BMD and cytokine production, which were
      evaluated using radiological scans, micro-CT, real-time quantitative PCR and
      ELISA. To analyse gene regulation by IL-19, rat synovial fibroblasts (SFs) were
      isolated and analysed for the expression of TNF-alpha, IL-1beta and RANK ligand
      (RANKL). RESULTS: In vivo, IL-19 was highly expressed in the synovial tissue and
      SFs isolated from CIA rats. 1BB1 significantly ameliorated the severity of
      arthritis by decreasing hind-paw thickness and swelling; prevented bone
      destruction and bone loss; inhibited the expression of TNF-alpha, IL-1beta, IL-6
      and RANKL in synovial tissue; and decreased the production of IL-6 in serum. In
      vitro, IL-19-induced TNF-alpha, IL-1beta, IL-6 and RANKL expression in CIA SFs.
      CONCLUSIONS: Specifically blocking IL-19 inhibited pro-inflammatory cytokine
      production and prevented bone destruction in CIA rats. These findings provide
      evidence that IL-19 is a novel target, and that anti-IL-19 antibody may be a
      potential target to ameliorate the severity of RA.

PMID- 21719424
TI  - Vitamin D levels in Chinese patients with systemic lupus erythematosus:
      relationship with disease activity, vascular risk factors and atherosclerosis.
AB  - OBJECTIVES: To study the relationship of 25(OH)D(3) level with disease activity,
      vascular risk factors and atherosclerosis in SLE. METHODS: Consecutive patients
      who fulfilled four or more ACR criteria for SLE were recruited for assay of
      25(OH)D(3) level. Disease activity was assessed by the SLEDAI and physicians'
      global assessment (PGA). Patients with vascular risk factors were screened for
      atherosclerosis at the coronary or carotid arteries. Correlation between
      25(OH)D(3) levels and SLEDAI scores was studied by linear regression. The link
      between vascular risk factors, atherosclerosis and vitamin D deficiency was also
      examined. RESULTS: A total of 290 SLE patients were studied [94% women; mean
      (s.d.) age 38.9 (13.1) years; disease duration 7.7 (6.7) years; 78% patients had
      clinical or serological lupus activity]. Two hundred and seventy-seven (96%)
      patients had vitamin D insufficiency [25(OH)D(3) < 30 ng/ml] and 77 (27%)
      patients had vitamin D deficiency (<15 ng/ml). Levels of 25(OH)D(3) correlated
      inversely with PGA (beta -0.20; P = 0.003), total SLEDAI scores (beta -0.19; P =
      0.003) and subscores due to active renal, musculoskeletal and haematological
      disease. Subjects with vitamin D deficiency had significantly higher total/high
      density lipoprotein (HDL) cholesterol ratio [3.96 (2.94) vs 3.07 (0.80); P =
      0.02] and prevalence of aPLs (57 vs 39%; P = 0.007). Of 132 patients, 58 (44%)
      with vascular risk factors screened were positive for subclinical
      atherosclerosis. No association could be demonstrated between 25(OH)D(3) level
      and atherosclerosis, which was mainly associated with increasing age, menopause,
      obesity and hyper-triglyceridaemia. CONCLUSIONS: In this large cross-sectional
      study of SLE patients, 25(OH)D(3) level correlates inversely with disease
      activity. Vitamin D deficiency is associated with dyslipidaemia. In patients with
      vascular risk factors, subclinical atherosclerosis is not associated with
      hypovitaminosis D.

PMID- 21719425
TI  - Pictures cueing threat: brain dynamics in viewing explicitly instructed danger
      cues.
AB  - Recent event-related brain potential studies revealed the selective processing of
      emotional and threatening pictures. Integrating the picture viewing and threat-of
      shock paradigm, the present study examined the processing of emotional pictures
      while they were explicitly instructed to cue threat of real world danger (i.e.
      electric shocks). Toward this end, 60 pleasant, neutral and unpleasant IAPS
      pictures were presented (1 s) as a continuous random stream while high-density
      EEG and self-reported threat were assessed. In three experimental runs, each
      picture category was used once as a threat-cue, whereas in the other conditions
      the same category served as safety-cue. An additional passive viewing run served
      as a no-threat condition, thus, establishing a threat-safety continuum (threat
      cue-safety-cue-no-threat) for each picture category. Threat-of-shock modulated
      P1, P2 and parieto-occipital LPP amplitudes. While the P1 component
      differentiated among threat- and no-threat conditions, the P2 and LPP effects
      were specific to pictures signaling threat-of-shock. Thus, stimulus processing
      progressively gained more accurate information about environmental threat
      conditions. Interestingly, the finding of increased EPN and centro-parietal LPP
      amplitudes to emotional pictures was independent from threat-of-shock
      manipulation. Accordingly, the results indicate distinct effects associated with
      the intrinsic significance of emotional pictures and explicitly instructed threat
      contingencies.

PMID- 21719426
TI  - Spurious hypophosphatemia associated with monoclonal paraproteinemia.

PMID- 21719427
TI  - Vitamin D and multiple sclerosis hospital admissions in Scotland.

PMID- 21719428
TI  - Accumulation of gamma- rather than alpha-tocopherol alters ethylene signaling
      gene expression in the vte4 mutant of Arabidopsis thaliana.
AB  - Tocopherols are antioxidants found in chloroplasts of leaves, and it is a matter
      of current debate whether or not they can affect signaling and gene expression in
      plant cells. For insight into the possible effects of altered tocopherol
      composition in chloroplasts on gene expression in the nucleus, the expression of
      ethylene biosynthesis, perception and signaling genes was investigated in vte1
      and vte4 Arabidopsis thaliana mutants, which are impaired in tocopherol (vitamin
      E) biosynthesis. Changes in gene expression were measured in plants exposed to
      either salt or water stress, and in young and mature leaves of vte1 and vte4
      mutants, which lack tocopherol cyclase and gamma-tocopherol methyltransferase,
      respectively. While transcript levels of ethylene signaling genes in the vte1
      mutant and the wild type were similar in all tested conditions, major changes in
      gene expression occurred in the vte4 mutant, particularly in mature leaves
      (compared with young leaves) and under salt stress. Accumulation of gamma-
      instead of alpha-tocopherol in this mutant led to elevated transcript levels of
      ethylene signaling pathway genes (particularly CTR1, EIN2, EIN3 and ERF1) in
      mature leaves of control plants. However, with salt treatment, transcript levels
      of most of these genes remained constant or dropped in the vte4 mutant, while
      they were dramatically induced in the wild type and the vte1 mutant. Furthermore,
      under salt stress, leaf age-induced jasmonic acid accumulated in both the vte1
      mutant and the wild type, but not in the vte4 mutant. It is concluded that
      jasmonic acid and ethylene signaling pathways are down-regulated in mature leaves
      of salt-stressed vte4 plants.

PMID- 21719429
TI  - Dravet syndrome as epileptic encephalopathy: evidence from long-term course and
      neuropathology.
AB  - Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by
      SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and
      neuropathology are not well known. We identified a series of 22 adult patients,
      including three adult post-mortem cases with Dravet syndrome. For all patients,
      we reviewed the clinical history, seizure types and frequency, antiepileptic
      drugs, cognitive, social and functional outcome and results of investigations. A
      systematic neuropathology study was performed, with post-mortem material from
      three adult cases with Dravet syndrome, in comparison with controls and a range
      of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female,
      were included, median age 39 years (range 20-66). SCN1A structural variation was
      found in 60% of the adult Dravet patients tested, including one post-mortem case
      with DNA extracted from brain tissue. Novel mutations were described for 11 adult
      patients; one patient had three SCN1A mutations. Features of Dravet syndrome in
      adulthood include multiple seizure types despite polytherapy, and age-dependent
      evolution in seizure semiology and electroencephalographic pattern. Fever
      sensitivity persisted through adulthood in 11 cases. Neurological decline
      occurred in adulthood with cognitive and motor deterioration. Dysphagia may
      develop in or after the fourth decade of life, leading to significant morbidity,
      or death. The correct diagnosis at an older age made an impact at several levels.
      Treatment changes improved seizure control even after years of drug resistance in
      all three cases with sufficient follow-up after drug changes were instituted;
      better control led to significant improvement in cognitive performance and
      quality of life in adulthood in two cases. There was no histopathological
      hallmark feature of Dravet syndrome in this series. Strikingly, there was
      remarkable preservation of neurons and interneurons in the neocortex and
      hippocampi of Dravet adult post-mortem cases. Our study provides evidence that
      Dravet syndrome is at least in part an epileptic encephalopathy.

PMID- 21719430
TI  - Abnormal functional lateralization and activity of language brain areas in
      typical specific language impairment (developmental dysphasia).
AB  - Atypical functional lateralization and specialization for language have been
      proposed to account for developmental language disorders, yet results from
      functional neuroimaging studies are sparse and inconsistent. This functional
      magnetic resonance imaging study compared children with a specific subtype of
      specific language impairment affecting structural language (n = 21), to a matched
      group of typically developing children using a panel of four language tasks
      neither requiring reading nor metalinguistic skills, including two auditory
      lexico-semantic tasks (category fluency and responsive naming) and two visual
      phonological tasks based on picture naming. Data processing involved normalizing
      the data with respect to a matched pairs paediatric template, groups and between
      groups analysis, and laterality indices assessment within regions of interest
      using single and combined task analysis. Children with specific language
      impairment exhibited a significant lack of left lateralization in all core
      language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus
      triangularis, supramarginal gyrus and superior temporal gyrus), across single or
      combined task analysis, but no difference of lateralization for the rest of the
      brain. Between-group comparisons revealed a left hypoactivation of Wernicke's
      area at the posterior superior temporal/supramarginal junction during the
      responsive naming task, and a right hyperactivation encompassing the anterior
      insula with adjacent inferior frontal gyrus and the head of the caudate nucleus
      during the first phonological task. This study thus provides evidence that this
      subtype of specific language impairment is associated with atypical
      lateralization and functioning of core language areas.

PMID- 21719431
TI  - Sources of variance in temporal and spatial aspects of jaw kinematics in two
      species of primates feeding on foods of different properties.
AB  - Chewing kinematics reflects interactions between centrally generated motor
      signals and peripheral sensory feedback from the constantly changing oral
      environment. Chewing is a strongly modulated behavior that responds to
      differences in material properties among different type of foods and to changes
      in the external physical properties of the food as the bolus gets processed.
      Feeding, as any complex biological behavior, presents variation at multiple
      hierarchical levels, from among species or higher-order levels to variation among
      chewing cycles within a single feeding sequence. Thus, to understand the
      mechanics and evolution of feeding systems requires estimation of how this
      variation is distributed across each of these hierarchical levels, which in turn
      requires large sample sizes. The development of affordable, high-resolution,
      three-dimensional kinematic recording systems has increased our ability to
      collect large amounts of data on complete or near-complete feeding sequences that
      can be used to shed light on the mechanisms of control in vertebrate feeding. In
      this study, we present data on the nature and sources of variation (from species
      to chewing cycle levels) in kinematics of chewing in two species of primates,
      Cebus and Macaca, while they feed on foods of known material properties.
      Variation in chewing kinematics was not evenly distributed among hierarchical
      levels. Most of the variation was observed among chewing cycles, most likely in
      response to changes in the external properties of the food bolus throughout the
      feeding sequence. Species differences were found in duration and vertical
      displacement during slow-close phase suggesting that each species exhibits
      different power stroke dynamics. Cebus exhibited more variable gape cycles than
      did Macaca, in particular when eating low-toughness foods. This increased ability
      to temporally and spatially modulate the gape cycle may reflect increased
      efficiency in processing food because Cebus monkeys use fewer, but longer cycles,
      than does Macaca when feeding on low-toughness foods. This is due to an increase
      in duration of the jaw-opening phases of the gape cycle, when the tongue
      repositions the food bolus in the oral cavity.

PMID- 21719432
TI  - Interspecific competition and torpor in golden spiny mice: two sides of the
      energy-acquisition coin.
AB  - We studied the occurrence of torpor in golden spiny mice in a hot rocky desert
      near the Dead Sea. In this rodent assemblage, a congener, the nocturnal common
      spiny mouse, competitively excluded the golden spiny mouse from the nocturnal
      part of the diel cycle and forced it into diurnal activity; this temporal
      partitioning allows the two species to partition their prey populations,
      particularly in summer when the diet of the two species is comprised mainly of
      arthropods, and largely overlap. We studied the effect of the presence of the
      common spiny mice at two resource levels (natural food availability and food
      added ad libitum) on populations of golden spiny mice in four large outdoor
      enclosures: two with common spiny mice removed and two enclosures with
      populations of both species. We hypothesized that with interspecific competition
      and/or reduced resources, golden spiny mice will increase their use of torpor. As
      we expected, supplemented food reduced the total time spent torpid. In summer,
      when the different activity periods of the two species results in prey species
      partitioning, removal of the congener did not affect torpor in the golden spiny
      mouse. However, in winter, when insect populations are low and the two species of
      mice overlap in a largely vegetarian diet, removal of the common spiny mouse
      reduced torpor in golden spiny mice, whether food was supplemented or not. This
      result suggests that torpor, a mechanism that allows small mammals to sustain
      periods of low availability of resources or high energetic requirements, may also
      help them to tolerate periods of enhanced interspecific competition. This may be
      a significant short-term mechanism that reduces competition and hence increases
      fitness, in particular of individuals of the subordinate species whose
      accessibility to resources may be limited.

PMID- 21719433
TI  - A preliminary analysis of correlated evolution in Mammalian chewing motor
      patterns.
AB  - Descriptive and quantitative analyses of electromyograms (EMG) from the jaw
      adductors during feeding in mammals have demonstrated both similarities and
      differences among species in chewing motor patterns. These observations have led
      to a number of hypotheses of the evolution of motor patterns, the most
      comprehensive of which was proposed by Weijs in 1994. Since then, new data have
      been collected and additional hypotheses for the evolution of motor patterns have
      been proposed. Here, we take advantage of these new data and a well-resolved
      species-level phylogeny for mammals to test for the correlated evolution of
      specific components of mammalian chewing motor patterns. We focus on the
      evolution of the coordination of working-side (WS) and balancing-side (BS) jaw
      adductors (i.e., Weijs' Triplets I and II), the evolution of WS and BS muscle
      recruitment levels, and the evolution of asynchrony between pairs of muscles. We
      converted existing chewing EMG data into binary traits to incorporate as much
      data as possible and facilitate robust phylogenetic analyses. We then tested
      hypotheses of correlated evolution of these traits across our phylogeny using a
      maximum likelihood method and the Bayesian Markov Chain Monte Carlo method. Both
      sets of analyses yielded similar results highlighting the evolutionary changes
      that have occurred across mammals in chewing motor patterns. We find support for
      the correlated evolution of (1) Triplets I and II, (2) BS deep masseter
      asynchrony and Triplets I and II, (3) a relative delay in the activity of the BS
      deep masseter and a decrease in the ratio of WS to BS muscle recruitment levels,
      and (4) a relative delay in the activity of the BS deep masseter and a delay in
      the activity of the BS posterior temporalis. In contrast, changes in relative WS
      and BS activity levels across mammals are not correlated with Triplets I and II.
      Results from this work can be integrated with dietary and morphological data to
      better understand how feeding and the masticatory apparatus have evolved across
      mammals in the context of new masticatory demands.

PMID- 21719434
TI  - Ecological and biomechanical insights into the evolution of gliding in mammals.
AB  - Gliding has evolved independently at least six times in mammals. Multiple
      hypotheses have been proposed to explain the evolution of gliding. These include
      the evasion of predators, economical locomotion or foraging, control of landing
      forces, and habitat structure. Here we use a combination of comparative methods
      and ecological and biomechanical data collected from free-ranging animals to
      evaluate these hypotheses. Our comparative data suggest that the origins of
      gliding are often associated with shifts to low-quality diets including leaves
      and plant exudates. Further, data from free-ranging colugos suggest that although
      gliding is not more energetically economical than moving through the canopy, it
      is much faster, allowing shorter times of transit between foraging patches and
      therefore more time available to forage in a given patch. In addition to moving
      quickly, gliding mammals spend only a small fraction of their overall time
      engaged in locomotion, likely offsetting its high cost. Kinetic data for both
      take-off and landing suggest that selection on these behaviors could also have
      shaped the evolution of gliding. Glides are initiated by high-velocity leaps that
      are potentially effective in evading arboreal predators. Further, upon landing,
      the ability to control aerodynamic forces and reduce velocity prior to impact is
      likely key to extending distances of leaps or glides while reducing the
      likelihood of injury. It is unlikely that any one of these hypotheses exclusively
      explains the evolution of gliding, but by examining gliding in multiple groups of
      extant animals in ecological and biomechanical contexts, new insights into the
      evolution of gliding can be gained.

PMID- 21719436
TI  - Laparoscopic splenectomy: learning curve comparison between benign and malignant
      disease.
AB  - BACKGROUND: New surgical techniques should be formally evaluated for feasibility
      and safety. As a model for this evaluation, this study examines the authors'
      institution's experience with splenectomy for benign and malignant hematologic
      disease since the introduction of laparoscopic splenectomy (LS) in 1996. The
      authors present the evaluation of the recognized surgeon/institutional learning
      curve using CUSUM (cumulative sum) analysis. METHODS: This is a single
      institution retrospective chart review of consecutive splenectomies for
      hematologic disease performed between 1996 and 2008. The primary outcome was
      conversion to open splenectomy. The learning curve for LS was evaluated using
      CUSUM analysis. RESULTS: A total of 123 splenectomies were performed for benign
      (51.2%) or malignant (48.7%) hematologic disease. 58% of patients underwent
      planned LS, with a 21% conversion rate. The surgeon's overall learning curves for
      LS, as well as that for malignant disease, were maintained within acceptable
      conversion thresholds. However, the learning curve for benign disease did cross
      the unacceptable conversion threshold at case 29. With additional experience, the
      curve again approached the acceptable conversion threshold. Patients with
      malignant disease were significantly older (P = .0004), had larger spleens (P =
      .0004), were more likely to undergo open splenectomy (P = .001), and had longer
      lengths of stay (P = .01). However, there was no significant difference in
      operative time, transfusion requirements, morbidity rates, or mortality rates
      between patients with benign and malignant disease. CONCLUSION: LS, for benign or
      for malignant hematologic disease, is associated with a significant learning
      curve. This evaluation model illustrates that careful patient selection and
      ongoing quality assessment is essential when introducing a new technique.

PMID- 21719437
TI  - Banked depopulated vena caval homograft: a new strategy to restore caval
      continuity.
AB  - This study reports one case of primary inferior vena cava (IVC) leiomyosarcoma. A
      67-year-old woman was referred to the authors' clinic for evaluation. She
      presented complaining of epigastric and right upper abdominal quadrant pain.
      Contrast-enhanced abdominal computed tomography scan revealed a 5.2 * 6.4 cm
      heterogeneously enhancing mass involving the anteromedial aspect of the IVC,
      below the renal vein (segment I), deforming the duodenum. There was a partial
      intraluminal extension in the IVC. Laparotomic resection was performed, with
      total en bloc excision of the lower IVC tumor. The caval continuity was restored
      with concomitant interposition of a banked depopulated vena cava homograft.
      Histological findings showed leiomyosarcoma originating from IVC. The
      postoperative course was uneventful: Neither recurrence nor metastasis was
      evident at 4 years postsurgery.

PMID- 21719438
TI  - A questionnaire survey to determine patient's knowledge, opinions and experience
      of acupuncture in an NHS GP practice.

PMID- 21719439
TI  - Prevalence of retinopathy in Finnish children and adolescents with type 1
      diabetes: a cross-sectional population-based retrospective study.
AB  - AIM: A population-based study was carried out to evaluate the prevalence and risk
      factors of diabetic retinopathy (DR) in children with type 1 diabetes (T1D) in
      The Northern Osthrobothnia Hospital District, Finland. The aim was to compare the
      current prevalence and the risk factors with those obtained in a study performed
      in a similar setting 17 years earlier. METHODS AND PATIENTS: The prevalence of DR
      was evaluated from fundus photographs in a cross-sectional manner in children and
      adolescents with T1D (n=297) living in the Northern Osthrobothnia Hospital
      District on 1 January 2007. RESULTS: The prevalence of DR was 7.6% (12/158) in
      males and 16.5% (23/139) in females in the present study and 7.3% in males and
      12.9% in females in the former study. The mean age of the patients was 11.9 and
      11.8 years, and the mean duration of diabetes was 4.9 and 5.0 years in the
      present and the former study, respectively. DR was associated with older age
      (p<0.001), longer duration of diabetes (p<0.001), higher glycated haemoglobin A1c
      (GHbA1c) (9.3% in those with DR vs 8.3% in those without DR, p=0.001, or 78 vs 67
      mmol/mol, respectively) and female sex (p=0.016); in a logistic regression
      analysis, these factors explained 35% of DR. These risk factors are essentially
      the same as identified in the cohort 17 years earlier. GHbA1c levels had not
      significantly improved during that time. CONCLUSIONS: The overall prevalence of
      DR among children with T1D was 11.8% (35/297) showing no decrease over the past
      17 years; in girls, DR was diagnosed more often in the present than in the former
      study, but there was no change in the prevalence among the boys. Glycaemic
      control had remained unchanged.

PMID- 21719440
TI  - Temporary brittle bone disease: the current position.

PMID- 21719441
TI  - Long term survival in children with acute leukaemia and complications requiring
      mechanical ventilation.
AB  - OBJECTIVE: Previous reports have indicated that the short term prognosis for
      patients with malignant diseases and serious adverse events requiring mechanical
      ventilation (SAEV) is improving. The purpose of this study was to determine
      whether these patients can be cured of malignant disease or whether they survive
      SAEV only to subsequently relapse. PATIENTS AND METHODS: The authors report the
      outcome of children with SAEV treated in the multicentre studies ALL-BFM 95 and
      AML-BFM 98. Data from 1182 patients with acute lymphoblastic leukaemia (ALL) and
      334 patients with acute myeloid leukaemia (AML) were analysed. 88 patients (51
      ALL and 37 AML) developed SAEV. RESULTS: The prognosis was almost identical in
      ALL and AML patients (survival of SAEV patients: 48%, 95% CI 38% to 58%; overall
      survival after 5 years: 31%, 95% CI 21% to 41%). Prognosis was independent of the
      time between leukaemia diagnosis and SAEV. Approximately 20% of children who
      required haemodialysis (n=14) or cardiac resuscitation (n=16) achieved long term
      survival, but no patient who fulfilled more than three of six identified risk
      factors (age >=10 years, high risk leukaemia, C reactive protein >=150 mg/l,
      administration of inotropic infusion, cardiac resuscitation and haemodialysis)
      survived (n=16; 0%, 95% CI 0% to 20%). CONCLUSIONS: Intensive care improves the
      short and long term survival of children with leukaemia. 64% (95% CI 50% to 78%)
      of children with acute leukaemia who survived SAEV achieved long term survival.
      Prognosis mainly depends on age and leukaemia risk group.

PMID- 21719442
TI  - Circumventing the WHO Code? An observational study.
AB  - BACKGROUND: This study compares the formula milk advertisements that appeared in
      parenting magazines published in two countries that have enacted measures to
      restrict the advertising of infant formula products in response to the
      international code with two that have not. METHODS: Content analysis was used to
      compare the type and frequency of formula milk advertisements that appeared in
      parenting magazines collected from the USA, Canada, the UK and Australia during
      2007, and to examine whether there was a relationship between these frequencies
      and advertising regulations. FINDINGS: Advertisements that promoted formula
      products or brands occurred in all of the magazines sampled but the type of
      product advertised differed. Follow-on formula advertisements occurred more
      frequently in titles from the UK, where infant formula advertising is prohibited
      (RR 3.82, 95% CI 2.65 to 5.50, p<0.0001) than they did in titles from the
      USA/Canada where infant and/or follow-on formula advertising is permitted.
      Toddler milk advertisements appeared more frequently in titles from Australia,
      where infant and follow-on formula advertising is prohibited, than they did in
      titles from countries where direct-to-consumer infant and/or follow-on formula
      advertising is permitted. Rate ratios were as follows: UK only 0.03 (95% CI 0.01
      to 0.11, p<0.0001); USA/Canada only 0.02 (95% CI 0.01 to 0.06, p<0.0001).
      INTERPRETATION: Bans on the advertising of infant formula products do not prevent
      companies from advertising (follow-on or toddler formula). These products are
      presented in ways that encourage consumers to associate the claims made in them
      with a group of products (a product line) that includes infant formula.

PMID- 21719443
TI  - Genetic activation of Nrf2 signaling is sufficient to ameliorate
      neurodegenerative phenotypes in a Drosophila model of Parkinson's disease.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder.
      Oxidative stress has been associated with the etiology of both sporadic and
      monogenic forms of PD. The transcription factor Nrf2, a conserved global
      regulator of cellular antioxidant responses, has been implicated in
      neuroprotection against PD pathology. However, direct evidence that upregulation
      of the Nrf2 pathway is sufficient to confer neuroprotection in genetic models of
      PD is lacking. Expression of the PD-linked gene encoding alpha-synuclein in
      dopaminergic neurons of Drosophila results in decreased locomotor activity and
      selective neuron loss in a progressive age-dependent manner, providing a
      genetically accessible model of PD. Here we show that upregulation of the Nrf2
      pathway by overexpressing Nrf2 or its DNA-binding dimerization partner, Maf-S,
      restores the locomotor activity of alpha-synuclein-expressing flies. Similar
      benefits are observed upon RNA-interference-mediated downregulation of the prime
      Nrf2 inhibitor, Keap1, as well as in conditions of keap1 heterozygosity.
      Consistently, the alpha-synuclein-induced dopaminergic neuron loss is suppressed
      by Maf-S overexpression or keap1 heterozygosity. Our data validate the sustained
      upregulation of the Nrf2 pathway as a neuroprotective strategy against PD. This
      model provides a genetically accessible in vivo system in which to evaluate the
      potential of additional Nrf2 pathway components and regulators as therapeutic
      targets.

PMID- 21719444
TI  - A high-sugar diet produces obesity and insulin resistance in wild-type
      Drosophila.
AB  - Insulin-resistant, 'type 2' diabetes (T2D) results from a complex interplay
      between genes and environment. In particular, both caloric excess and obesity are
      strongly associated with T2D across many genetic backgrounds. To gain insights
      into how dietary excess affects insulin resistance, we studied the simple model
      organism Drosophila melanogaster. Larvae reared on a high-sugar diet were
      hyperglycemic, insulin resistant and accumulated fat--hallmarks of T2D--compared
      with those reared on control diets. Excess dietary sugars, but not fats or
      proteins, elicited insulin-resistant phenotypes. Expression of genes involved in
      lipogenesis, gluconeogenesis and beta-oxidation was upregulated in high-sugar-fed
      larvae, as were FOXO targets, consistent with known mechanisms of insulin
      resistance in humans. These data establish a novel Drosophila model of diet
      induced insulin resistance that bears strong similarity to the pathophysiology of
      T2D in humans.

PMID- 21719445
TI  - Phenotypic associations of genetic susceptibility loci in systemic lupus
      erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus is a clinically heterogeneous autoimmune
      disease. A number of genetic loci that increase lupus susceptibility have been
      established. This study examines if these genetic loci also contribute to the
      clinical heterogeneity in lupus. MATERIALS AND METHODS: 4001 European-derived,
      1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped
      for 16 confirmed lupus susceptibility loci. Ancestry informative markers were
      genotyped to calculate and adjust for admixture. The association between the risk
      allele in each locus was determined and compared in patients with and without the
      various clinical manifestations included in the ACR criteria. RESULTS: Renal
      disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0
      * 10(-6), OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI
      1.07 to 1.25). Other significant findings include the association between risk
      alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM
      and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection
      from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and
      haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these
      associations are significant with a false discovery rate of <0.05 and pass the
      significance threshold using Bonferroni correction for multiple testing.
      CONCLUSION: Signifi cant associations were found between clinical manifestations
      and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that
      genetic profiling might be a useful tool to predict disease manifestations in
      lupus patients in the future.

PMID- 21719446
TI  - Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B
      core antibody-positive rheumatoid arthritis patients undergoing anti-tumour
      necrosis factor alpha therapy.
AB  - OBJECTIVE: To investigate the kinetics of hepatitis B virus (HBV) viral loads and
      HBV reactivation in rheumatoid arthritis (RA) patients undergoing therapy with
      tumour necrosis factor alpha (TNFalpha) inhibitors. METHODS: The authors
      investigated the virological, serological and biochemical evidence of HBV
      reactivation in 88 RA patients receiving anti-TNFalpha therapy. Levels of HBV
      surface (HBs) antigen (Ag), anti-HBV core (HBc)-IgG and anti-HBs antibody (Ab)
      were detected by electrochemiluminescence immunoassay, and viral loads were
      determined by real-time PCR assay. RESULTS: In a total of 88 HBcAb-positive
      patients, 18 (20.5%) patients were HBsAg-positive, 12 (13.6%) patients were HBsAg
      negative/HBsAb-negative and 58 (65.9%) patients were HBsAg-negative/HBsAb
      positive before starting anti-TNFalpha therapy. Among HBsAg-positive patients
      receiving anti-TNFalpha therapy, HBV reactivation was documented in none of 10
      patients who received lamivudine pre-emptive therapy and serum viral loads
      significantly decreased (mean +/- SEM, 153,860 +/- 80,120 IU/ml at baseline vs
      313 +/- 235 IU/ml after 12 months antiviral therapy, p<0.001), paralleling the
      decrease in serum aminotransferase levels. In contrast, five (62.5%) of eight
      patients without antiviral prophylaxis developed HBV reactivation, viral loads
      significantly increased after anti-TNFalpha therapy (9375 +/- 5924 IU/ml vs
      49,710,000 +/- 40,535,000 IU/ml, p<0.001), and markedly declined after antiviral
      therapy (49,710,000 +/- 40,535,000 IU/ml vs 6382 +/- 2424 IU/ml, p<0.001).
      Baseline viral loads were detectable in four (33.3%) of 12 patients who had HBsAg
      negative/HBsAb-negative status, and one developed HBV reactivation after anti
      TNFalpha therapy. CONCLUSION: HBV reactivation can occur in both HBsAg-positive
      and HBsAg-negative/HBcAb-positive patients with detectable HBV DNA, so-called
      occult HBV infection, during anti-TNFalpha therapy. Antiviral prophylaxis may
      effectively reduce HBV reactivation in HBsAg-positive RA patients undergoing anti
      TNFalpha therapy.

PMID- 21719447
TI  - Small and medium-size physician practices use few patient-centered medical home
      processes.
AB  - The patient-centered medical home has become a prominent model for reforming the
      way health care is delivered to patients. The model offers a robust system of
      primary care combined with practice innovations and new payment methods. But
      scant information exists about the extent to which typical US physician practices
      have implemented this model and its processes of care, or about the factors
      associated with implementation. In this article we provide the first national
      data on the use of medical home processes such as chronic disease registries,
      nurse care managers, and systems to incorporate patient feedback, among 1,344
      small and medium-size physician practices. We found that on average, practices
      used just one-fifth of the patient-centered medical home processes measured as
      part of this study. We also identify internal capabilities and external
      incentives associated with the greater use of medical home processes.

PMID- 21719448
TI  - Relationship between peak cardiac pumping capability and selected exercise
      derived prognostic indicators in patients treated with left ventricular assist
      devices.
AB  - AIM: Exercise-derived variables have been used in the assessment of functional
      capacity and prognosis in patients with chronic heart failure. The aim of this
      study was to assess the relationship between cardiac pumping capability
      represented by peak cardiac power output and peak oxygen consumption, anaerobic
      threshold, ventilatory efficiency slope, and peak circulatory power in patients
      undergoing the 'Harefield Protocol'. METHODS AND RESULTS: Haemodynamic and gas
      exchange measurements were undertaken during a graded treadmill exercise test.
      They were performed on 54 patients-18 implanted with left ventricular assist
      devices (LVADs), 16 explanted (recovered), and 20 moderate-to-severe heart
      failure patients. Peak oxygen consumption was only highly correlated with peak
      cardiac power output in explanted LVAD (r = 0.85, P< 0.01), but not in implanted
      LVAD and heart failure patients (r = 0.55 and 0.53, P< 0.05). The anaerobic
      threshold was only modestly correlated with peak cardiac power output in heart
      failure and explanted (r = 0.46 and 0.54, P< 0.05) and weakly in implanted LVAD
      patients (r = 0.37, P< 0.05). Peak cardiac power output was well correlated with
      peak circulatory power in LVAD explanted and implanted (r = 0.82, P< 0.01; r =
      0.63, P< 0.01) but not in heart failure patients (r = 0.31, P> 0.05). Ventilatory
      efficiency slope was only moderately correlated with peak cardiac power output in
      LVAD-explanted patients (r = -0.52, P< 0.05). CONCLUSION: Exercise-derived
      prognostic indicators demonstrate limited capacity in reflecting cardiac pumping
      capability in patients treated with LVADs and should therefore be used with
      caution in interpretation of cardiac organ function.

PMID- 21719449
TI  - Can emerging biomarkers of myocardial remodelling identify asymptomatic
      hypertensive patients at risk for diastolic dysfunction and diastolic heart
      failure?
AB  - AIMS: Hypertension is one of the main drivers of the heart failure (HF) epidemic.
      The aims of this study were to profile fibro-inflammatory biomarkers across
      stages of the hypertensive heart disease (HHD) spectrum and to examine whether
      particular biochemical profiles in asymptomatic patients identify a higher risk
      of evolution to HF. METHODS AND RESULTS: This was a cross-sectional observational
      study involving a population of 275 stable hypertensive patients divided into two
      different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF
      with preserved ejection fraction  (n= 181). Asymptomatic hypertension patients
      were further subdivided according to left atrial volume index >=34 mL/m(2) (n=
      30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers
      [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1
      (MCP1), and tumour necrosis factor alpha], collagen 1 and 3 metabolic markers
      [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen
      1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal
      telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix
      metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue
      inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide.
      Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart
      failure with preserved ejection fraction  was associated with an increased
      inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP
      and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations
      in MMP and TIMP enzymes were found to be significant indicators of greater
      degrees of asymptomatic left ventricular diastolic dysfunction. CONCLUSION: These
      data define varying fibro-inflammatory profiles throughout different stages of
      HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of
      earlier detection of those at risk of evolution to HF which may help focus
      effective preventative strategies.

PMID- 21719450
TI  - A marker of mayhem: macrovolt T-wave alternans preceding polymorphic ventricular
      tachycardia.

PMID- 21719451
TI  - Prevalence of cardiovascular disease risk factor in the Chinese population: the
      2007-2008 China National Diabetes and Metabolic Disorders Study.
AB  - AIMS: Cardiovascular disease (CVD) is now the most prevalent and debilitating
      disease affecting the Chinese population. The goal of the present manuscript was
      to analyse cardiovascular risk factors and the prevalence of non-fatal CVDs from
      data gathered from the 2007-2008 China National Diabetes and Metabolic Disorders
      Study. METHODS AND RESULTS: A nationally representative sample of 46 239 adults,
      20 years of age or older, was randomly recruited using a multistage stratified
      design method. Lifestyle factors, diagnosis of CVD, stroke, diabetes, and family
      history of each subject were collected, and an oral glucose tolerance test or a
      standard meal test was performed. Various non-fatal CVDs were reported by the
      subjects. SUDAAN software was used to perform all weighted statistical analyses,
      with P < 0.05 considered statistically significant. The prevalence of coronary
      heart disease, stroke, and CVDs was 0.74, 1.07, and 1.78% in males; and 0.51,
      0.60, and 1.10% in females, respectively. The presence of CVDs increased with age
      in both males and females. The prevalence of being overweight or obese,
      hypertension, dyslipidaemia, or hyperglycaemia was 36.67, 30.09, 67.43, and
      26.69% in males; and 29.77, 24.79, 63.98, and 23.62% in females, respectively. In
      the total sample of 46 239 patients, the prevalence of one subject having 1, 2,
      3, or >=4 of the 5 defined risk factors (i.e. smoking, overweight or obese,
      hypertension, dyslipidaemia, or hyperglycaemia) was 31.17, 27.38, 17.76, and
      10.19%, respectively. Following adjustment for gender and age, the odds ratio of
      CVDs for those who had 1, 2, 3, or >=4 risk factors was 2.36, 4.24, 4.88, and
      7.22, respectively, when compared with patients with no risk factors. CONCLUSION:
      Morbidity attributed to the five defined cardiovascular risk factors was high in
      the Chinese population, with multiple risk factors present in the same
      individual. Therefore, reasonable prevention strategies should be designed to
      attenuate the rapid rise in cardiovascular morbidity.

PMID- 21719452
TI  - Effect of upstream clopidogrel treatment in patients with ST-segment elevation
      myocardial infarction undergoing primary percutaneous coronary intervention.
AB  - AIMS Immediate treatment with a loading dose of clopidogrel at diagnosis of ST
      segment elevation myocardial infarction (STEMI) is recommended by ESC/AHA/ACC
      guidelines in patients eligible for primary percutaneous coronary intervention
      (PCI). However, the evidence for this practice is scarce. METHODS AND RESULTS All
      patients who underwent PCI for STEMI in Sweden between 2003 and 2008 were
      identified from the national Swedish Coronary Angiography and Angioplasty
      Registry (SCAAR). Patients with concomitant warfarin treatment and patients not
      having received aspirin upstream were excluded, leaving 13 847 patients for the
      analysis. Groups were compared for death and myocardial infarction (MI) during 1
      year of follow-up using Cox regression models with adjustment for differences in
      baseline characteristics by propensity score methods. The combined primary
      endpoint of death or MI during 1-year follow-up occurred in 1325 of 9813 patients
      with upstream clopidogrel and in 364 out of 4034 patients without upstream
      treatment. After propensity score adjustment, a significant relative risk
      reduction (HR 0.82, 95% CI 0.73-0.93) in death/MI at 1 year was observed. The
      secondary endpoint of total 1-year death was significantly reduced (HR 0.76, 95%
      CI: 0.64-0.90), while the incidence of 1-year MI did not show any significant
      reduction (HR 0.90, 95% CI 0.77-1.06). Similar results were observed in
      multivariate analysis on top of propensity scoring and in sensitivity analyses
      excluding patients without clopidogrel and aspirin at discharge. CONCLUSION This
      large observational study suggests that upstream clopidogrel treatment prior to
      arrival at the catheterization lab is associated with a reduction in the combined
      risk of death or MI as well as death alone in patients with STEMI treated with
      primary PCI.

PMID- 21719453
TI  - Rupturing aortic dissection.

PMID- 21719454
TI  - More about plasma renin and cardiovascular mortality.

PMID- 21719455
TI  - Coronary CT angiographic characteristics of culprit lesions in acute coronary
      syndromes not related to plaque rupture as defined by optical coherence
      tomography and angioscopy.
AB  - AIMS: Pathological and clinical optical coherence tomography (OCT) studies have
      indicated that acute coronary syndrome (ACS) lesions have either ruptured fibrous
      caps (RFC-ACS) or intact fibrous caps (IFC-ACS). Although computed tomographic
      (CT) angiographic characteristics of RFC-ACS include low-attenuation plaques and
      positive plaque remodelling, features associated with IFC-ACS have not been
      previously described. The aim of this study was to assess the CT characteristics
      of IFC-ACS lesions. METHODS AND RESULTS: Seventy-four patients with ACS/stable
      angina consented to multimodality imaging, of which 66 underwent CT angiography.
      Of these, 57 culprit lesions in 57 patients were evaluated with sufficient image
      quality from all four of OCT, angioscopy, intravascular ultrasound, and CT
      angiography. Intraluminal thrombus was assessed by OCT/angioscopy, and culprit
      lesions further classified by OCT-based demonstration of fibrous cap integrity.
      Of 35 culprit lesions with ACS, OCT revealed IFC with thrombus in 10 (29%) and
      RFC in the remaining 25 (71%); all 22 lesions with stable angina had intact
      fibrous caps. Fibrous caps were significantly thinner in RFC-ACS than IFC-ACS and
      stable angina (45 +/- 12, 131 +/- 57, and 321 +/- 146 MUm, respectively; P =
      0.001). CT angiography revealed that low-attenuation plaques were more frequently
      observed in RFC-ACS than IFC-ACS and stable angina (88, 40, and 18%; P = 0.001)
      lesions. Similarly, positive remodelling was more predominantly seen in RFC-ACS
      than IFC-ACS and stable angina (96, 20, and 14%; P = 0.001). However, none of the
      specific CT angiography features clearly distinguished IFC-ACS from stable
      lesions. CONCLUSION: In contrast to the situation with RFC-ACS, distinct culprit
      lesion characteristics associated with non-rupture-related mechanisms are not
      identified by CT angiography. It will therefore not be possible to differentiate
      plaques likely to develop IFC-ACS from stable plaques.

PMID- 21719456
TI  - Aldosterone, mortality, and acute ischaemic events in coronary artery disease
      patients outside the setting of acute myocardial infarction or heart failure.
AB  - BACKGROUND: Recent studies have demonstrated that aldosterone levels measured in
      patients with heart failure or acute myocardial infarction (MI) are associated
      with long-term mortality, but the association with aldosterone levels in patients
      with coronary artery disease (CAD) outside these specific settings remains
      unknown. In addition, no clear mechanism has been elucidated to explain these
      observations. The present study was designed to evaluate the relationship between
      the level of aldosterone and the risk of death and acute ischaemic events in CAD
      patients with a preserved left ventricular (LV) function and no acute MI. METHODS
      AND RESULTS: In 799 consecutive CAD patients referred for elective coronary
      angioplasty measurements were obtained before the procedure for: aldosterone
      (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC
      reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction
      (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required
      urgent revascularization were not included in the study. The primary endpoint,
      cardiovascular death, occurred in 41 patients during a median follow-up period of
      14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute
      MI or ischaemic stroke), and the composite of death and acute ischaemic events
      were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was
      found to be related to BMI, hypertension and NYHA class, and inversely related to
      age, creatinine clearance, and use of beta-blockers. Multivariate Cox model
      analysis demonstrated that aldosterone was independently associated with
      cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute
      ischaemic events (P = 0.01), and the composite of death and acute ischaemic
      events (P = 0.004). Reclassification analysis, using integrated discrimination
      improvement (IDI) and net reclassification improvement (NRI), demonstrated
      incremental predictive value of aldosterone (P < 0.0001). CONCLUSION: Our results
      demonstrate that, in patients with CAD but without heart failure or acute MI, the
      level of aldosterone is strongly and independently associated with mortality and
      the occurrence of acute ischaemic events.

PMID- 21719457
TI  - Interventricular septum rupture after transcatheter aortic valve implantation.

PMID- 21719458
TI  - Failure of CT coronary imaging to identify plaque erosion: a resetting of
      expectations.

PMID- 21719459
TI  - The relation between self-reported body weight and health-related quality of
      life: a cross-sectional study in Japan.
AB  - BACKGROUND: Whilst being obese is associated with increased mortality, less is
      known about the relationship between body weight and health-related quality of
      life (HRQOL). We aimed to examine this relationship in the general Japanese
      population, focusing on both underweight and overweight individuals. METHODS: We
      cross sectionally analyzed data from the Health Diary Study, which surveyed
      health-related behavior in a nationally quasi-representative sample from 2003.
      HRQOL was measured using the Short Form-8 Health Survey. Body mass index (BMI)
      was calculated from self-reported height and weight values. We compared
      differences in HRQOL in people with normal BMI (18.5-24.9) with those with
      underweight (<18.5), overweight (25-29.9) or obese (>=30) BMIs. RESULTS: Among a
      population-weighted random sample (5387 households), 1857 households (34.5%)
      agreed to participate. Of the targeted sample population (3658 people), 3477
      responded (95.1%). Of 2453 people (age >=18 years), we analyzed data from 2399
      people. After adjusting for age, sex and status of chronic conditions, we found
      that being overweight was correlated with impaired physical HRQOL [coefficient:
      0.96 (95% confidence interval (CI): -1.73, -0.20)] but not with mental HRQOL
      [coefficient: -0.17 (95% CI: -0.50, 0.95)]. CONCLUSIONS: Although the differences
      were small, being overweight was correlated with impaired physical HRQOL but not
      with mental HRQOL.

PMID- 21719460
TI  - Evaluation of the Bcl-2 family antagonist ABT-737 in collagen-induced arthritis.
AB  - Therapeutic manipulation of cellular apoptosis holds great promise for malignant
      and potentially nonmalignant diseases. A relative resistance to apoptosis in RA
      synovium is associated with increased expression of prosurvival Bcl-2 family
      members. In this study, we demonstrate that treatment of DBA/1 mice, prior to the
      onset of CIA with ABT-737, a BH3 mimetic targeting Bcl-2, Bcl-w, and Bcl-x(L),
      ameliorated disease development. In contrast, treatment of mice with ABT-737 in
      established CIA did not alter the course of disease. ABT-737 induced lymphopenia,
      however pathogenic lymphoid populations in CIA mice were less affected, as shown
      by relatively normal T and B cell responses to CII. Naive lymphocytes were highly
      sensitive to apoptosis after culture with ABT-737, but synovial macrophages and
      neutrophils were not. Mcl-1 was detected in synovial monocyte/macrophages and
      neutrophils and strikingly, its expression, rather than Bcl-2 and Bcl-x(L),
      increased in the affected paws and lymphoid organs of mice with CIA. These
      observations implicate Mcl-1, which is not targeted by ABT-737, in the survival
      of inflammatory cells in established CIA and suggest that antagonism of Mcl-1 may
      be more effective in diseases such as RA.

PMID- 21719461
TI  - Editorial: Counting the carbs: a memory B cell makeover.

PMID- 21719462
TI  - Editorial: Serine proteases, serpins, and neutropenia.

PMID- 21719463
TI  - Elucidation of the contribution of active site and exosite interactions to
      affinity and specificity of peptidylic serine protease inhibitors using non
      natural arginine analogs.
AB  - There is increasing interest in developing peptides for pharmacological
      intervention with pathophysiological functions of serine proteases. From phage
      displayed peptide libraries, we previously isolated peptidylic inhibitors of
      urokinase-type plasminogen activator, a potential target for intervention with
      cancer invasion. The two peptides, upain-1 (CSWRGLENHRMC) and mupain-1
      (CPAYSRYLDC), are competitive inhibitors of human and murine urokinase-type
      plasminogen activator, respectively. Both have an Arg as the P1 residue,
      inserting into the S1 pocket in the active site of the enzymes, but their
      specificity depends to a large extent on interactions outside the enzymes' active
      sites, so-called exosite interactions. Here we describe upain-2 (CSWRGLENHAAC)
      and the synthesis of a number of upain-2 and mupain-1 variants in which the P1
      Arg was substituted with novel non-natural Arg analogs and achieved considerable
      improvement in the affinity of the peptides to their targets. Using chimeras of
      human and murine urokinase-type plasminogen activator as well as X-ray
      crystallography, we delineated the relative contribution of the P1 residue and
      exosite interactions to the affinity and specificity of the inhibitors for their
      target enzyme. The effect of inserting a particular non-natural amino acid into
      the P1 position is determined by the fact that changes in interactions of the P1
      residue in the S1 pocket lead to changed exosite interactions and vice versa.
      These findings are of general interest when the affinities and specificities of
      serine protease inhibitors to be used for pharmacological intervention are
      considered and could pave the way for potential drug candidates for the treatment
      of cancer.

PMID- 21719464
TI  - Structural and functional analyses of the second-generation integrase strand
      transfer inhibitor dolutegravir (S/GSK1349572).
AB  - Raltegravir (RAL) and related HIV-1 integrase (IN) strand transfer inhibitors
      (INSTIs) efficiently block viral replication in vitro and suppress viremia in
      patients. These small molecules bind to the IN active site, causing it to
      disengage from the deoxyadenosine at the 3' end of viral DNA. The emergence of
      viral strains that are highly resistant to RAL underscores the pressing need to
      develop INSTIs with improved resistance profiles. Herein, we show that the
      candidate second-generation drug dolutegravir (DTG, S/GSK1349572) effectively
      inhibits a panel of HIV-1 IN variants resistant to first-generation INSTIs. To
      elucidate the structural basis for the increased potency of DTG against RAL
      resistant INs, we determined crystal structures of wild-type and mutant prototype
      foamy virus intasomes bound to this compound. The overall IN binding mode of DTG
      is strikingly similar to that of the tricyclic hydroxypyrrole MK-2048. Both
      second-generation INSTIs occupy almost the same physical space within the IN
      active site and make contacts with the beta4-alpha2 loop of the catalytic core
      domain. The extended linker region connecting the metal chelating core and the
      halobenzyl group of DTG allows it to enter farther into the pocket vacated by the
      displaced viral DNA base and to make more intimate contacts with viral DNA,
      compared with those made by RAL and other INSTIs. In addition, our structures
      suggest that DTG has the ability to subtly readjust its position and conformation
      in response to structural changes in the active sites of RAL-resistant INs.

PMID- 21719466
TI  - In infants with 'colic'/persistent crying, administration of daily Lactobacillus
      reuteri DSM 17938 was associated with reduced crying time at 1, 2 and 3 weeks.

PMID- 21719465
TI  - Novel thiosemicarbazone iron chelators induce up-regulation and phosphorylation
      of the metastasis suppressor N-myc down-stream regulated gene 1: a new strategy
      for the treatment of pancreatic cancer.
AB  - Pancreatic cancer is an aggressive neoplasm, with a mortality rate close to 100%.
      The most successful agent for pancreatic cancer treatment is gemcitabine,
      although the overall effect in terms of patient survival remains very poor. This
      study was initiated to evaluate a novel class of anticancer agents against
      pancreatic cancer. This group of compounds belongs to the dipyridyl
      thiosemicarbazone class that have been shown to have potent and selective
      activity against a range of different neoplasms in vitro and in vivo. We
      demonstrate for the first time in pancreatic cancer that these agents increase
      the expression of the growth and metastasis suppressor N-myc downstream-regulated
      gene 1 and its phosphorylation at Ser330 and Thr346 that is important for its
      activity against this tumor. In addition, these agents increased expression of
      the cyclin-dependent kinase inhibitor p21(CIP1/WAF1), whereas decreasing cyclin
      D1 in pancreatic cancer cells. Together, these molecular alterations account, in
      part, for the pronounced antitumor activity observed. Indeed, these agents had
      significantly higher antiproliferative activity in vitro than the established
      treatments for pancreatic cancer, namely gemcitabine and 5-fluorouracil. Studies
      in vivo demonstrated that a novel thiosemicarbazone, namely di-2-pyridylketone 4
      cyclohexyl-4-methyl-3-thiosemicarbazone hydrochloride, completely inhibited the
      growth of pancreatic cancer xenografts with no evidence of marked alterations in
      normal tissue histology. Together, our studies have identified molecular
      effectors of a novel and potent antitumor agent that could be useful for
      pancreatic cancer treatment.

PMID- 21719467
TI  - Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal
      truncated Nle1-angiotensin IV analogs.
AB  - Angiotensin IV (AngIV; Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6))-related
      peptides have emerged as potential antidementia agents. However, their
      development as practical therapeutic agents has been impeded by a combination of
      metabolic instability, poor blood-brain barrier permeability, and an incomplete
      understanding of their mechanism of action. This study establishes the core
      structure contained within norleucine(1)-angiotensin IV (Nle(1)-AngIV) that is
      required for its procognitive activity. Results indicated that Nle(1)-AngIV
      derived peptides as small as tetra- and tripeptides are capable of reversing
      scopolamine-induced deficits in Morris water maze performance. This
      identification of the active core structure contained within Nle(1)-AngIV
      represents an initial step in the development of AngIV-based procognitive drugs.
      The second objective of the study was to clarify the general mechanism of action
      of these peptides by assessing their ability to affect changes in dendritic
      spines. A correlation was observed between a peptide's procognitive activity and
      its capacity to increase spine numbers and enlarge spine head size. These data
      suggest that the procognitive activity of these molecules is attributable to
      their ability to augment synaptic connectivity.

PMID- 21719469
TI  - Influence of tissue integrity on pharmacological phenotypes of muscarinic
      acetylcholine receptors in the rat cerebral cortex.
AB  - Distinct pharmacological phenotypes of muscarinic acetylcholine receptors
      (mAChRs) have been proposed. We compared the pharmacological profiles of mAChRs
      in intact segments and homogenates of rat cerebral cortex and other tissues by
      using radioligand binding assays with [(3)H]N-methylscopolamine ([(3)H]NMS).
      Recombinant M(1) and M(3) mAChRs were also examined. The density of mAChRs
      detected by [(3)H]NMS binding to rat cerebral cortex segments and homogenates was
      the same (approximately 1400 fmol/mg tissue protein), but the dissociation
      constant of [(3)H]NMS was significantly different (1400-1700 pM in segments and
      260 pM in homogenates). A wide variation in [(3)H]NMS binding affinity was also
      observed among the segments of other tissues (ranging from 139 pM in urinary
      bladder muscle to 1130 pM in the hippocampus). The mAChRs of cerebral cortex were
      composed of M(1), M(2), M(3), and M(4) subtypes, which showed typical subtype
      pharmacology in the homogenates. However, in the cortex segments the M(3) subtype
      showed a low selectivity for M(3) antagonists (darifenacin, solifenacin) and was
      not distinguished by the M(3) antagonists from the other subtypes. Recombinant
      M(1) and M(3) mAChRs showed high affinity for [(3)H]NMS and subtype-specific
      pharmacology for each tested ligand. The present binding study under conditions
      where tissue integrity was kept demonstrates a wide variation in [(3)H]NMS
      binding affinity among mAChRs of many rat tissues and the presence of an atypical
      M(3) phenotype in the cerebral cortex, suggesting that the pharmacological
      properties of mAChRs are not necessarily constant, rather they may be
      significantly modified by tissue integrity and tissue type.

PMID- 21719468
TI  - Blockade of endocannabinoid hydrolytic enzymes attenuates precipitated opioid
      withdrawal symptoms in mice.
AB  - Delta(9)-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis
      sativa, has long been known to reduce opioid withdrawal symptoms. Although THC
      produces most of its pharmacological actions through the activation of CB(1) and
      CB(2) cannabinoid receptors, the role these receptors play in reducing the
      variety of opioid withdrawal symptoms remains unknown. The endogenous
      cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2
      arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly
      metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase
      (MAGL), respectively. The objective of this study was to test whether increasing
      AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces
      naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models
      of opioid dependence. Morphine-dependent mice challenged with naloxone reliably
      displayed a profound withdrawal syndrome, consisting of jumping, paw tremors,
      diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4
      (dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose
      dependently reduced the intensity of most measures through the activation of
      CB(1) receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine
      dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5
      (trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845)
      reduced the intensity of naloxone-precipitated jumps and paw flutters through the
      activation of CB(1) receptors but did not ameliorate incidence of diarrhea or
      weight loss. In the final series of experiments, we investigated whether JZL184
      or PF-3845 would attenuate naloxone-precipitated contractions in morphine
      dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone
      induced contractions, although this model does not account mechanistically for
      the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These
      results indicate that endocannabinoid catabolic enzymes are promising targets to
      treat opioid dependence.

PMID- 21719470
TI  - Inactivation of mrcA gene derepresses the basal-level expression of L1 and L2
      beta-lactamases in Stenotrophomonas maltophilia.
AB  - OBJECTIVES: To characterize the relationship between inactivation of the mrcA
      gene and beta-lactamase expression and beta-lactams resistance in
      Stenotrophomonas maltophilia KJ and to investigate the involvement of ampR, ampN
      ampG, ampD(I) and creBC in this. METHODS: The mrcA deletion mutant KJDeltamrcA
      was constructed to investigate the role of this putative penicillin-binding
      protein 1a (PBP1a) in beta-lactamase expression and beta-lactam resistance. The
      DeltaampR, DeltaampNG, DeltaampDI and DeltacreBC alleles were introduced into
      KJDeltamrcA, and KJDeltaDIDeltaBC and KJDeltaDIDeltamrcADeltaBC were also
      constructed for comparison. All the mutants and their corresponding parent
      strains were assayed for beta-lactamase activities and MICs of beta-lactams.
      RESULTS: Inactivation of mrcA caused basal L1/L2 beta-lactamase production to
      increase by ~100-fold, but made little difference to cefuroxime-induced beta
      lactamase activity and the MICs of beta-lactams. The DeltamrcA-derived basal beta
      lactamase hyperproduction was ampR and ampN-ampG dependent. Simultaneous
      inactivation of ampD(I) and mrcA did not augment beta-lactamase production over
      and above that seen in an ampD(I) mutant alone. Furthermore, we could find no
      evidence for a role of the creBC two-component regulatory system in beta
      lactamase hyperproduction in a DeltaampD(I) or DeltamrcA background. CONCLUSIONS:
      Inactivation of mrcA, predicted to encode PBP1a, causes basal L1/L2 beta
      lactamase hyperproduction in S. maltophilia.

PMID- 21719471
TI  - Eradication of carriage with methicillin-resistant Staphylococcus aureus:
      determinants of treatment failure.
AB  - BACKGROUND: Using data from an observational study in which the effectiveness of
      a guideline for eradication of methicillin-resistant Staphylococcus aureus (MRSA)
      carriage was evaluated, we identified variables that were associated with
      treatment failure. METHODS: A multivariate logistic regression model was
      performed with subgroup analyses for uncomplicated and complicated MRSA carriage
      (the latter including MRSA infection, skin lesions, foreign-body material,
      mupirocin resistance and/or exclusive extranasal carriage) and for those treated
      according to the guideline (i.e. mupirocin nasal ointment and chlorhexidine soap
      solution for uncomplicated carriage, in combination with two oral antibiotics for
      complicated carriage). RESULTS: Six hundred and thirteen MRSA carriers were
      included, of whom 333 (54%) had complicated carriage; 327 of 530 patients (62%)
      with known complexity of carriage were treated according to the guideline with an
      absolute increase in treatment success of 20% (95% confidence interval 12%-28%).
      Among those with uncomplicated carriage, guideline adherence [adjusted odds ratio
      (OR(a)) 7.4 (1.7-31.7)], chronic pulmonary disease [OR(a) 44 (2.9-668)], throat
      carriage [OR(a) 2.9 (1.4-6.1)], perineal carriage [OR(a) 2.2 (1.1-4.4)] and
      carriage among household contacts [OR(a) 5.6 (1.2-26)] were associated with
      treatment failure. Among those with complicated carriage, guideline adherence was
      associated with treatment success [OR(a) 0.2 (0.1-0.3)], whereas throat carriage
      [OR(a) 4.4 (2.3-8.3)] and dependence in activities of daily living [OR(a) 3.6
      (1.4-8.9)] were associated with failure. CONCLUSIONS: Guideline adherence,
      especially among those with complicated MRSA carriage, was associated with
      treatment success. Adding patients with extranasal carriage or dependence in
      daily self-care activities to the definition of complicated carriage, and
      treating them likewise, may further increase treatment success.

PMID- 21719472
TI  - Cigarette smoking and risk of subsequent use of antibacterials: a follow-up of
      365,117 men and women.
AB  - OBJECTIVES: Antibacterial prescribing is driving antibiotic resistance. We aimed
      to analyse whether smoking habits are associated with susceptibility to be
      prescribed antibacterials in primary care and to examine whether patients'
      smoking habits influence physicians' choice of therapy. METHODS: Information on
      smoking habits from health surveys in 1985-99 was related to use of
      antibacterials 5-25 years later by linkage to the Norwegian Prescription
      Database. The study population included 365 117 men and women, 40-45 years old.
      Individuals likely to have chronic obstructive airway disease were excluded.
      Relative risk (RR) of being dispensed antibacterials for systemic use was
      calculated for five levels of smoking intensity with never smokers as reference.
      Adjustments were made for age, education, marital status, household size, body
      mass index and residence (rural/urban). RESULTS: Fifty-six percent of the male
      and 69% of the female never smokers received at least one antibacterial
      prescription in the whole period, increasing to 68% and 82%, respectively, in
      heavy smokers (>19 cigarettes/day) (adjusted RR 1.17 and 1.16). The percentage
      receiving at least one antibacterial prescription every year was 0.5% in male and
      1.9% in female never smokers, increasing to 1.1% and 4.0%, respectively, in heavy
      smokers (adjusted RR 2.07 and 1.89). The proportion of antibacterial users who
      were prescribed broad-spectrum antibacterials increased with increasing cigarette
      consumption. CONCLUSIONS: Smoking habits influenced the usage of antibacterials
      years later with a dose-response relationship. Prescribers seem to acknowledge
      smoking as a risk factor for resistant bacteria since broad-spectrum
      antibacterials are more frequently prescribed to smokers than never smokers.

PMID- 21719473
TI  - Eradication of carriage with methicillin-resistant Staphylococcus aureus:
      effectiveness of a national guideline.
AB  - BACKGROUND: We evaluated the effectiveness of eradication of methicillin
      resistant Staphylococcus aureus (MRSA) carriage in the Netherlands after the
      introduction of a guideline in 2006. The guideline distinguishes complicated
      (defined as the presence of MRSA infection, skin lesions, foreign-body material,
      mupirocin resistance and/or exclusive extranasal carriage) and uncomplicated
      carriage (not meeting criteria for complicated carriage). Mupirocin nasal
      ointment and chlorhexidine soap solution are recommended for uncomplicated
      carriers and the same treatment in combination with two oral antibiotics for
      complicated carriage. METHODS: A prospective cohort study was performed in 18
      Dutch centres from 1 October 2006 until 1 October 2008. RESULTS: Six hundred and
      thirteen MRSA carriers underwent one or more decolonization treatments during the
      study period, mostly after hospital discharge. Decolonization was achieved in 367
      (60%) patients with one eradication attempt and ultimately 493 (80%) patients
      were decolonized, with a median time until decolonization of 10 days
      (interquartile range 7-43 days). Three hundred and twenty-seven (62%) carriers
      were treated according to the guideline, which was associated with an absolute
      increase in treatment success of 20% [from 45% (91/203) to 65% (214/327)].
      CONCLUSIONS: Sixty percent of MRSA carriers were successfully decolonized after
      the first eradication attempt and 62% were treated according to the guideline,
      which was associated with an increased treatment success.

PMID- 21719474
TI  - Disparities in testing for renal function in UK primary care: cross-sectional
      study.
AB  - BACKGROUND: In the UK, explicit quality standards for chronic disease management,
      including for diabetes and chronic kidney disease (CKD), are set out National
      Service Frameworks and pay-for-performance indicators. These conditions are
      common with a prevalence of 4% and 5.4%, respectively. CKD is largely
      asymptomatic, detected following renal function testing and important because
      associated with increased mortality and morbidity, especially in people with
      diabetes and proteinuria. OBJECTIVES: To investigate who has their renal function
      tested and any association with age, sex, ethnicity and diabetes. METHOD: A cross
      sectional survey in a primary care research network in south-west London (n = 220
      721). The following data were extracted from routine data: age, gender,
      ethnicity, latest serum creatinine, diagnosis of diabetes and recording of
      proteinuria. We used logistic regression to explore any association in testing
      for CKD. RESULTS: People (82.1%) with diabetes had renal function and proteinuria
      tested; the proportion was much smaller (<0.5%) in those without. Women were more
      likely to have a creatinine test than men (28% versus 24%, P < 0.05), but this
      association was modified by age, ethnicity and presence of diabetes. People >75
      years and with diabetes were most likely to have been tested. Black [adjusted
      odds ratio (AOR) 2.1, 95% confidence interval (CI) 2.0-2.2] and south Asian (AOR
      1.65, 95% CI 1.56-1.75) patients were more likely to be tested than whites. Those
      where ethnicity was not stated were the only group not tested more than whites.
      CONCLUSIONS: Quality improvement initiatives and equity audits, which include CKD
      should take account of disparities in renal function testing.

PMID- 21719475
TI  - A trifle of management.

PMID- 21719476
TI  - Does quality improvement face a legitimacy crisis? Poor quality studies, small
      effects.

PMID- 21719477
TI  - Emergency respiratory admissions: influence of practice, population and hospital
      factors.
AB  - OBJECTIVE: To determine the influence of population, hospital and general
      practice characteristics on practice admission rates for asthma and chronic
      obstructive pulmonary disease (COPD) in England. METHODS: Cross sectional study
      using Hospital Episode Statistics (HES), routine population data and primary care
      data. Admissions for all general practices in England during 2005-06, adjusted
      for age and sex composition of practice population. Univariable analysis of
      population, practice and hospital care provision variables, including prevalence
      and quality data. Significant factors included in multiple regression Poisson
      model. RESULTS: Admissions from 8169 practices were included. Risk of admission
      for each condition increased with deprivation, prevalence and smoking. Admission
      rates were higher in urban than rural practices. Hospital bed availability and
      distance to the nearest emergency department were also significantly associated
      with risk of admission. The associations with practice factors including practice
      size and quality markers varied across conditions. CONCLUSIONS: Practice
      population, geographic and hospital supply factors are consistently associated
      with asthma and COPD admissions. Higher smoking rates among such patients in a
      practice are associated with higher admission rates. There is little evidence
      from this study that other modifiable general practice factors are important in
      influencing admission rates.

PMID- 21719478
TI  - Marginal costs of hospital-acquired conditions: information for priority-setting
      for patient safety programmes and research.
AB  - OBJECTIVE: To estimate the relative inpatient costs of hospital-acquired
      conditions. METHODS: Patient level costs were estimated using computerized
      costing systems that log individual utilization of inpatient services and apply
      sophisticated cost estimates from the hospital's general ledger. Occurrence of
      hospital-acquired conditions was identified using an Australian 'condition-onset'
      flag for diagnoses not present on admission. These were grouped to yield a
      comprehensive set of 144 categories of hospital-acquired conditions to summarize
      data coded with ICD-10. Standard linear regression techniques were used to
      identify the independent contribution of hospital-acquired conditions to costs,
      taking into account the case-mix of a sample of acute inpatients (n = 1,699,997)
      treated in Australian public hospitals in Victoria (2005/06) and Queensland
      (2006/07). RESULTS: The most costly types of complications were post-procedure
      endocrine/metabolic disorders, adding AU$21,827 to the cost of an episode,
      followed by MRSA (AU$19,881) and enterocolitis due to Clostridium difficile
      (AU$19,743). Aggregate costs to the system, however, were highest for septicaemia
      (AU$41.4 million), complications of cardiac and vascular implants other than
      septicaemia (AU$28.7 million), acute lower respiratory infections, including
      influenza and pneumonia (AU$27.8 million) and UTI (AU$24.7 million). Hospital
      acquired complications are estimated to add 17.3% to treatment costs in this
      sample. CONCLUSIONS: Patient safety efforts frequently focus on dramatic but rare
      complications with very serious patient harm. Previous studies of the costs of
      adverse events have provided information on 'indicators' of safety problems
      rather than the full range of hospital-acquired conditions. Adding a cost
      dimension to priority-setting could result in changes to the focus of patient
      safety programmes and research. Financial information should be combined with
      information on patient outcomes to allow for cost-utility evaluation of future
      interventions.

PMID- 21719479
TI  - Evaluating 'success' in programme budgeting and marginal analysis: a literature
      review.
AB  - OBJECTIVES: Programme budgeting and marginal analysis (PBMA) is a priority
      setting toolkit which aims to assist decision-makers in identifying the most
      efficient use of resources. The last systematic literature review on PBMA was
      published in 2001 and evaluated success in applying PBMA using the criteria of
      'reallocation of resources' or the 'setting of priorities'. Our objective was to
      re-evaluate applications of PBMA in terms of these criteria separately, summarize
      different evaluation methods of PBMA and extend the above review by considering
      all PBMA applications since 2001. METHODS: Systematic literature review.
      Information was sought from four general medical electronic databases.
      Descriptive statistics and content analysis were used. RESULTS: PBMA was
      successful in 52% of cases when success was defined in terms of the participants
      gaining a better understanding of the area under interest; in 65% of cases when
      success was defined as 'implementation of all or some of the advisory panel's
      recommendations'; in 48% of the studies when success was defined in terms of
      disinvesting or resource reallocation; and in 22% when success was defined in
      terms of adopting the framework for future use. CONCLUSIONS: The rate of success
      is clearly influenced by how success is defined. There is a need for a broadly
      accepted definition of success to be used when evaluating PBMA applications so to
      enable direct comparisons of studies. This evaluatory component needs to be
      adjacent to PBMA and not a separate procedure.

PMID- 21719480
TI  - Utility of clinical risk predictors for preoperative cardiovascular risk
      prediction.
AB  - Cardiovascular risk prediction using clinical risk factors is integral to both
      the European and the American algorithms for preoperative cardiac risk assessment
      and perioperative management for non-cardiac surgery. We have reviewed these risk
      factors and their ability to guide clinical decision making. We examine their
      limitations and attempt to identify factors which may improve their performance
      when used for clinical risk stratification. To improve the performance of the
      clinical risk factors, it is necessary to create uniformity in the definitions of
      both cardiovascular outcomes and the clinical risk factors. The risk factors
      selected should reflect the degree of organ dysfunction rather than a historical
      diagnosis. Parsimonious model design should be applied, making use of a minimal
      number of continuous variables rather than creating overfitted models. The
      inclusion of age in the model may assist partly in controlling for the duration
      of risk factor exposure. Risk assignment should occur throughout the
      perioperative period and the risk factors chosen for model inclusion should vary
      depending on when the assignment occurs (before operation, intraoperatively, or
      after operation).

PMID- 21719481
TI  - Rehabilitation and acute exacerbations.
AB  - Recent evidence indicates that acute exacerbations of chronic obstructive
      pulmonary disease aggravate the extrapulmonary consequences of the disease.
      Skeletal muscle dysfunction, a sustained decrease in exercise tolerance, enhanced
      symptoms of depression and fatigue are reported. Avoidance of physical activities
      is likely to be a key underlying mechanism and increases the risk of new
      exacerbations. Pulmonary rehabilitation is an intervention targeting these
      systemic consequences. Exercise strategies need to be adapted to the increased
      feelings of dyspnoea and fatigue. This review aims to describe the systemic
      consequences of acute exacerbations and compiles evidence for the feasibility and
      effectiveness of different rehabilitation strategies to counteract these
      consequences during and/or immediately after the acute phase of the exacerbation.
      Resistance training and neuromuscular electrical stimulation have been applied
      safely in frail, hospitalised patients and have the potential to prevent muscle
      atrophy. Comprehensive pulmonary rehabilitation, including general exercise
      training, can be implemented immediately after the exacerbation, leading to a
      reduction in hospital admissions and an increase in exercise tolerance and
      quality of life. Self-management strategies play a crucial role in changing
      disease-related health behaviour and preventing hospital admissions.

PMID- 21719482
TI  - IkappaBalpha glutathionylation and reduced histone H3 phosphorylation inhibit
      eotaxin and RANTES.
AB  - Airway smooth muscle cells (ASMCs) secrete eotaxin and RANTES (regulated on
      activation, normal T-cell expressed and secreted) in response to tumour necrosis
      factor (TNF)-alpha, which is inhibited by the nuclear factor (NF)-kappaB
      inhibitor dimethylfumarate (DMF). NF-kappaB/IkappaB (inhibitor of NF-kappaB)
      glutathionylation and changes in chromatin remodelling can inhibit NF-kappaB
      activity. In this study, we determined whether NF-kappaB/IkappaB
      glutathionylation and reduced histone H3 phosphorylation might underlie the
      inhibitory effect of DMF on NF-kappaB activity, and eotaxin and RANTES secretion.
      Primary human ASMCs were treated with DMF, diamide and/or glutathione (GSH)
      ethylester (OEt) prior to TNF-alpha stimulation and were subsequently analysed by
      ELISA, electrophoretic mobility shift assay, immunofluorescence, co
      immunoprecipitation or immunoblotting. DMF reduced intracellular GSH and induced
      IkappaBalpha glutathionylation (IkappaBalpha-SSG), which inhibited IkappaBalpha
      degradation, NF-kappaB p65 nuclear entry and NF-kappaB/DNA binding. In addition,
      DMF inhibited the phosphorylation of histone H3, which was possibly mediated by
      the inhibitory effect of DMF on mitogen- and stress-activated protein kinase
      (MSK)-1. However, p38 mitogen-activated protein kinase (MAPK), extracellular
      signal-regulated kinase MAPK and MAPK phosphatase-1, upstream of MSK-1, were not
      inhibited by DMF. Importantly, DMF-mediated effects on NF-kappaB, histone H3,
      eotaxin and RANTES were reversed by addition of GSH-OEt. Our data suggest that
      DMF inhibits NF-kappaB-dependent eotaxin and RANTES secretion by reduction of GSH
      with subsequent induction of IkappaBalpha-SSG and inhibition of histone H3
      phosphorylation. Our findings offer new potential drug targets to reduce airway
      inflammation in asthma.

PMID- 21719483
TI  - Lack of an exaggerated inflammatory response on virus infection in cystic
      fibrosis.
AB  - Respiratory virus infections play an important role in cystic fibrosis (CF)
      exacerbations, but underlying pathophysiological mechanisms are poorly
      understood. We aimed to assess whether an exaggerated inflammatory response of
      the airway epithelium on virus infection could explain the increased
      susceptibility of CF patients towards respiratory viruses. We used primary
      bronchial and nasal epithelial cells obtained from 24 healthy control subjects
      and 18 CF patients. IL-6, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, RANTES/CCL5 and
      GRO-alpha/CXCL1 levels in supernatants and mRNA expression in cell lysates were
      measured before and after infection with rhinoviruses (RV-16 and RV-1B) and RSV.
      Cytotoxicity was assessed by lactate dehydrogenate assay and flow cytometry. All
      viruses induced strong cytokine release in both control and CF cells. The
      inflammatory response on virus infection was heterogeneous and depended on cell
      type and virus used, but was not increased in CF compared with control cells. On
      the contrary, there was a marked trend towards lower cytokine production
      associated with increased cell death in CF cells. An exaggerated inflammatory
      response to virus infection in bronchial epithelial cells does not explain the
      increased respiratory morbidity after virus infection in CF patients.

PMID- 21719484
TI  - Rescue of murine silica-induced lung injury and fibrosis by human embryonic stem
      cells.
AB  - Alveolar type II pneumocytes (ATII cells) are considered putative alveolar stem
      cells. Since no treatment is available to repair damaged epithelium and prevent
      lung fibrosis, novel approaches to induce regeneration of injured alveolar
      epithelium are desired. The objective of this study was to assess both the
      capacity of human embryonic stem cells (HUES-3) to differentiate in vitro into
      ATII cells and the ability of committed HUES-3 cells (HUES-3-ATII cells) to
      recover in vivo a pulmonary fibrosis model obtained by silica-induced damage. In
      vitro differentiated HUES-3-ATII cells displayed an alveolar phenotype
      characterised by multi-lamellar body and tight junction formation, by the
      expression of specific markers such as surfactant protein (SP)-B, SP-C and zonula
      occludens (ZO)-1 and the activity of cystic fibrosis transmembrane conductance
      regulator-mediated chloride ion transport. After transplantation of HUES-3-ATII
      cells into silica-damaged mice, histological and biomolecular analyses revealed a
      significant reduction of inflammation and fibrosis markers along with lung
      function improvement, weight recovery and increased survival. The persistence of
      human SP-C, human nuclear antigen and human DNA in the engrafted lungs indicates
      that differentiated cells remained engrafted up to 10 weeks. In conclusion, cell
      therapy using HUES-3 cells may be considered a promising approach to lung injury
      repair.

PMID- 21719485
TI  - RNA is favourable for analysing EGFR mutations in malignant pleural effusion of
      lung cancer.
AB  - Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation
      of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing
      of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation
      detection. To test whether EGFR analysis from RNA is less prone to interference
      from nontumour cells that have no or lower EGFR expression, we compared three
      methods (sequencing from cell-derived RNA versus sequencing and mass
      spectrometric analysis from genomic DNA), in parallel, for EGFR mutation
      detection from MPE samples in 150 lung adenocarcinoma patients receiving first
      line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations
      were much more frequently identified by sequencing using RNA than by sequencing
      and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus
      44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%,
      respectively). The better mutation detection yield of sequencing from RNA was
      coupled with the superior prediction of clinical efficacy of first-line TKIs. In
      patients with acquired resistance, EGFR sequencing from RNA provided satisfactory
      detection of T790M (54.2%). These results demonstrated that EGFR sequencing using
      RNA as template greatly improves sensitivity for EGFR mutation detection from
      samples of MPE, highlighting RNA as the favourable source for analysing EGFR
      mutations from heterogeneous MPE specimens in NSCLC.

PMID- 21719486
TI  - TOF-SIMS analysis of exhaled particles from patients with asthma and healthy
      controls.
AB  - Particles in exhaled air (PEx) may reflect the composition of respiratory tract
      lining fluid (RTLF); thus, there is a need to assess their potential as sources
      of biomarkers for respiratory diseases. In the present study, we compared PEx
      from patients with asthma and controls using time-of-flight-secondary ion mass
      spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using
      an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed
      asthma and 11 nonsmoking healthy controls performed 10 consecutive forced
      exhalations into the instrument. Particle concentrations were recorded and
      samples of particles collected on silicon plates were analysed by TOF-SIMS.
      Subjects with asthma exhaled significantly lower numbers of particles than
      controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was
      significantly lower in samples from subjects with asthma (0.25 versus 0.35;
      p=0.036). Orthogonal partial least squares-discriminant analysis models showed
      good separation between both positive and negative spectra. Molecular ions from
      phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to
      discriminate the groups. We conclude that analysis of PEx is a promising method
      to examine the composition of RTLF. In the present explorative study, we could
      discriminate between subjects with asthma and healthy controls based on TOF-SIMS
      spectra from PEx.

PMID- 21719487
TI  - Interferon release does not add discriminatory value to smear-negative HIV
      tuberculosis algorithms.
AB  - Clinical algorithms for evaluating HIV-infected individuals for tuberculosis (TB)
      prior to isoniazid preventive therapy (IPT) perform poorly, and interferon-gamma
      release assays (IGRAs) have moderate accuracy for active TB. It is unclear
      whether, when used as adjunct tests, IGRAs add any clinical discriminatory value
      for active TB diagnosis in the pre-IPT assessment. 779 sputum smear-negative HIV
      infected persons, established on or about to commence combined antiretroviral
      therapy (ART), were screened for TB prior to IPT. Stepwise multivariable logistic
      regression was used to develop clinical prediction models. The discriminatory
      ability was assessed by receiver operator characteristic area under the curve
      (AUC). QuantiFERON-TB Gold in-tube (QFT-GIT) was evaluated. The prevalence of
      smear-negative TB by culture was 6.4% (95% CI 4.9-8.4%). Used alone, QFT-GIT and
      the tuberculin skin test (TST) had comparable performance; the post-test
      probability of disease based on single negative tests was 3-4%. In a
      multivariable model, the QFT-GIT test did not improve the ability of a clinical
      algorithm, which included not taking ART, weight <60 kg, no prior history of TB,
      any one positive TB symptom/sign (cough >= 2 weeks) and CD4+ count <250 cells per
      mm(3), to discriminate smear-negative culture-positive and -negative TB (72% to
      74%; AUC comparison p=0.33). The TST marginally improved the discriminatory
      ability of the clinical model (to 77%, AUC comparison p=0.04). QFT-GIT does not
      improve the discriminatory ability of current TB screening clinical algorithms
      used to evaluate HIV-infected individuals for TB ahead of preventive therapy.
      Evaluation of new TB diagnostics for clinical relevance should follow a
      multivariable process that goes beyond test accuracy.

PMID- 21719488
TI  - The burden of TB-HIV in the EU: how much do we know? A survey of surveillance
      practices and results.
AB  - Information on the burden of tuberculosis (TB)-HIV co-infection is critical for
      the planning and evaluation of TB-HIV control and treatment strategies. This
      study assessed current practices in countries of the European Union (EU) and
      European Economic Area (EEA) for monitoring HIV co-infection in TB surveillance
      systems, countries' current co-infection burden and associated clinical practice.
      An online survey was distributed to all national TB surveillance nominated
      European Centre for Disease Prevention and Control contact points in the EU/EEA.
      We received 25 responses from 30 countries (83% response rate). Patients' HIV
      status was collected in 18 out of the 25 TB surveillance systems, usually via
      clinician reporting (16 out of 18 surveillance systems). Although most countries
      recommended routine testing of TB patients for HIV, the proportion actually
      tested varied from 5% to 90%. The burden of HIV co-infection was found to be
      elevated in countries with higher levels of HIV testing and higher prevalence of
      HIV. We suggest that TB-HIV co-infection be monitored in all EU/EEA countries to
      facilitate the planning and evaluation of TB-HIV control strategies.
      Strengthening collaboration between TB and HIV clinicians and surveillance
      departments, and consideration of patient confidentiality restraints would be
      advantageous. The level of HIV testing in TB patients is low despite national
      recommendations and testing should be further promoted and monitored.

PMID- 21719489
TI  - Pulmonary manifestations of immunoglobulin G4-related sclerosing disease.
AB  - Immunoglobulin (Ig)G4-related sclerosing disease (ISD) (also called IgG4-related
      systemic disease, IgG4-related disease or hyper-IgG4 disease) is a recently
      described systemic fibroinflammatory disease associated with elevated circulating
      levels of IgG4. Although initial descriptions of this disorder focused on its
      pancreatic presentation (autoimmune pancreatitis), it has become apparent that
      ISD is a systemic disease with many facets. The lesion of ISD is characterised by
      lymphoplasmacytic inflammation, fibrosis, phlebitis and increased numbers of IgG4
      positive plasma cells. The disease can either be localised to one or two organs,
      or be present with diffuse multi-organ disease. Furthermore, lesions in different
      organs can present simultaneously or metachronously. In the thorax, lesions
      associated with ISD have been described in the lung parenchyma, airways and
      pleura, as well as the mediastinum. Data published to date suggest that ISD may
      account for a portion of various fibroinflammatory conditions of unknown cause
      encountered in the chest, including inflammatory pseudotumours, idiopathic
      interstitial pneumonias, fibrosing mediastinitis, inflammatory pleural lesions
      and, occasionally, airway disease. Some aspects of pulmonary manifestations
      attributed to ISD remain controversial and additional studies are needed to
      clarify the relationship along with the increasing relevance of this disorder to
      pulmonary medicine.

PMID- 21719490
TI  - Effect of an ambulatory diagnostic and treatment programme in patients with sleep
      apnoea.
AB  - The aim of this study to evaluate the efficacy of a home-based programme on
      clinical response, continuous positive airway pressure (CPAP) compliance and cost
      in a population of high pre-test probability of suffering obstructive sleep
      apnoea syndrome (OSAS). Patients were randomised into the following three groups.
      Group A: home respiratory polygraphy (RP) and home follow-up; group B: hospital
      polysomnography and hospital follow-up; and group C: home RP and hospital follow
      up. Evaluation during 6 months included Epworth Sleepiness Scale (ESS),
      Functional Outcomes Sleep Questionnaire (FOSQ), and daily activity and symptom
      questionnaires. Compliance was assessed by memory cards (group A) and using an
      hourly counter (groups B and C). 66 patients were included (22 per branch), 83%
      were males, aged mean+/-sd 52+/-10 yrs, body mass index 34+/-7kg.m(-2),
      apnoea/hypopnoea index 43+/-20 h(-1), CPAP pressure 8+/-2 cmH(2)O, with no
      between-group differences. Clinical response showed an ESS of mean+/-sd 15+/-3 to
      6+/-4, a FOSQ of 16+/-3 to 18+/-2, symptoms of 43+/-7 to 25+/-7, and activity of
      37+/-11 to 25+/-8. At the end of the study, compliance was: group A 73%, group B
      68% and group C 57%. The cost per patient was: group A ?590+/-43, group B ?894+/
      11 and group C ?644+/-93 (p<0.001). In conclusion, patients with a high initial
      probability of having OSAS can be diagnosed and treated in a home setting, with a
      high level of CPAP compliance and lower cost than using either a hospital-based
      approach or home RP/hospital follow-up.

PMID- 21719491
TI  - Airflow limitation, lung volumes and systemic inflammation in a general
      population.
AB  - Although several levels of evidence have suggested an association between
      systemic inflammation and spirometric lung volumes, data addressing the potential
      interrelationship between airflow limitation and inflammatory markers are sparse
      and remain controversial. Potential associations between high-sensitivity C
      reactive protein (hsCRP), fibrinogen and lung function were investigated in 1,466
      individuals aged 25-85 yrs, representing a general population. Within this cross
      sectional population, data on body plethysmography, spirometry, helium dilution
      and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were analysed.
      After adjustment for potential confounding factors, such as smoking, obesity and
      cardiorespiratory fitness, there was an inverse association of hsCRP with forced
      expiratory and static lung volumes. In neither apparently healthy nor the entire
      population was inflammation associated with airflow limitation in central
      airways. In smokers only, higher hsCRP and fibrinogen were associated with an
      impaired D(L,CO). This study shows that higher levels of hsCRP are associated
      with decreased lung volumes in a general population over a wide age range. A
      consistent interrelationship of central airflow limitation and inflammation was
      not verifiable. Smoking is related to an impaired D(L,CO) in association with an
      increase in systemic inflammation.

PMID- 21719492
TI  - Airways changes related to air pollution exposure in wheezing children.
AB  - In this study, we aimed to evaluate the relationship between individual total
      exposure to air pollution and airway changes in a group of 51 wheezing children.
      Respiratory status was assessed four times (January 2006, June 2006, January 2007
      and June 2007) during a 1-week period through a standardised questionnaire,
      spirometry, exhaled nitric oxide fraction and pH in exhaled breath condensate
      (EBC). Concentrations of particles with a 50% cut-off aerodynamic diameter of 10
      um (PM(10)), O(3), NO(2) and volatile organic compounds were estimated through
      direct measurements with an ad hoc device or air pollution modelling in the
      children's schools and at their homes in the same 4 weeks of the study. For each
      child, total exposure to the different air pollutants was estimated as a function
      of pollutant concentrations and daily activity patterns. Increasing total
      exposure to PM(10), NO(2), benzene, toluene and ethylbenzene was significantly
      associated with a decrease of forced expiratory volume in 1 s (FEV(1)) and with
      an increase of change in FEV(1). Increasing exposure to NO(2) and benzene was
      also related to a significant decrease of FEV(1)/forced vital capacity.
      Increasing exposure to PM(10), NO(2), benzene and ethylbenzene was associated
      with acidity of EBC. This study suggests an association in wheezing children
      between airway changes and total exposure to air pollutants, as estimated by
      taking into account the concentration in the various microenvironments attended
      by the children.

PMID- 21719494
TI  - Are COPD patients with pneumonia who are taking inhaled corticosteroids at higher
      risk of dying?

PMID- 21719495
TI  - Playing a dirty trick on airway smooth muscle: house dust mite does it again.

PMID- 21719496
TI  - What is this thing called somnolence?

PMID- 21719497
TI  - Prescribing and guidelines: both must improve to combat antimicrobial resistance.

PMID- 21719498
TI  - MMPs are regulatory enzymes in pathways of inflammatory disorders, tissue injury,
      malignancies and remodelling of the lung.

PMID- 21719499
TI  - Fully reversible pulmonary arterial hypertension associated with dasatinib
      treatment for chronic myeloid leukaemia.

PMID- 21719500
TI  - Influence of pre-analytic conditions on the rate of indeterminate T-SPOT.TB
      tests.

PMID- 21719501
TI  - Is multidrug-resistant tuberculosis on the rise in Mozambique? Results of a
      national drug resistance survey.

PMID- 21719502
TI  - Attitudes, training and smoking profile of European Respiratory Society members.

PMID- 21719503
TI  - Shorter treatment duration for selected patients with multidrug-resistant
      tuberculosis.

PMID- 21719504
TI  - Diagnosis of tuberculosis in patients with psoriasis: the need for a modified
      approach.

PMID- 21719506
TI  - Internal consistency of reference equations.

PMID- 21719508
TI  - Validation of the human chorionic gonadotropin immunoassay in cerebrospinal fluid
      for the diagnostic work-up of neurohypophyseal germinomas.
AB  - BACKGROUND: The measurement of human chorionic gonadotropin (hCG) in
      cerebrospinal fluid (CSF) is useful for the differential diagnosis of suprasellar
      lesions. However, the concentrations that prove diagnostic for neurohypophyseal
      germinoma have not been well defined. In addition, the immunoassays used for such
      measurements are the same as those applied in serum, and few studies have been
      performed regarding the validation of such techniques in CSF. The present study
      aims to apply the Elecsys((r)) hCG + beta immunoassay from Roche Diagnostics to
      measure hCG in CSF, as a useful tool in the diagnosis of neurohypophyseal
      germinomas in children and young adults. METHODS: Validation of the immunoassay
      involved calculation of the functional sensitivity and reference values for hCG
      in CSF in 35 controls in the absence of pregnancy, trophoblastic disease or
      tumour pathology. For the clinical application study, three patients diagnosed
      with neurohypophyseal germinoma have been reviewed. RESULTS: The functional
      sensitivity obtained was 0.4 IU/L. The reference values for hCG in CSF ranged
      from undetectable values to 0.7 IU/L. The hCG concentrations in CSF in the three
      studied patients, with confirmed diagnosis of neurohypophyseal germinoma, were
      21.1, 32.6 and 23 IU/L, respectively. CONCLUSIONS: The Elecsys(r) hCG + beta
      immunoassay from Roche Diagnostics can be used to detect hCG in CSF with high
      precision. According to our results, CSF-hCG concentrations that exceed the
      established reference interval (undetectable values to 0.7 IU/L) in the presence
      of suprasellar lesions and hypophyseal stalk thickening must be considered
      pathological, establishing the need to exclude the presence of germinoma.

PMID- 21719509
TI  - Immunoglobulin E deficiency: a forgotten clue pointing to possible
      immunodeficiency?
AB  - BACKGROUND: Patients with primary antibody deficiency often have delayed
      diagnosis. Very low IgE, found during investigations for allergy, may be a marker
      for other immunodeficiency. METHODS: We introduced a new laboratory policy of
      testing cases with very low IgE levels for possible linked antibody deficiency.
      The data represent an audit of routine results collected over two years. RESULTS:
      Very low IgE (<=2 IU/mL) was identified in 85/2622 (3.2%) routine patient
      samples. Two children and four adult patients were found to have one or more
      classes of immunoglobulin below the reference range for age. In 2/6, the
      initiative of the laboratory led to a new unsuspected diagnosis of antibody
      immunodeficiency. CONCLUSIONS: Common variable immunodeficiency continues to be
      overlooked as a primary cause of lung disease in adults. Very low serum IgE
      should trigger appropriate investigation (immunoglobulin quantification and serum
      electrophoresis).

PMID- 21719510
TI  - EDTA contamination of serum samples: common but not necessarily significant.

PMID- 21719511
TI  - Does the introduction of duty-hour restriction in the United States negatively
      affect the operative volume of surgical trainees?
AB  - Over the last few years, both sides of the North Atlantic have witnessed
      compulsory duty-hour restrictions for doctors. It has been suggested that the
      reduction in working hours for surgeons in training may have a negative impact on
      their exposure to surgical procedures and therefore, on the quality of training.
      A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: among surgeons enrolled in a training
      program, does the introduction of duty-hour restrictions have a negative impact
      on their exposure to surgical procedures and therefore, on the quality of
      training? In total, more than 74 papers were found using the reported search, of
      which 15 represented the best evidence to answer the question. All these
      manuscripts came from the USA. The authors, journal, date and country of
      publication, group studied, study type, relevant outcomes and results of these
      papers are tabulated. Studies from different surgical disciplines, such as
      general, orthopedic, pediatric, cardiothoracic and vascular surgery were
      included. Among the studies analysed, eight revealed a decrease, five showed no
      change, and two studies demonstrated an increase in the operative experience of
      residents following the introduction of the 80-hour limit. The changes appear to
      have more negatively affected junior residents in favor of more senior ones due
      to a shift in the surgical workload to the latter. Interestingly, some studies
      demonstrated better results in the in-training examinations (testing for clinical
      and basic science knowledge) following the duty-hour restrictions. We conclude
      that although most of the studies included in this review revealed that the
      introduction of working-hour restrictions in the USA has produced a decrease in
      number of cases performed by trainees, some have failed to do so. Changes in the
      residents' working patterns, such as 'night float' and 'leave early' models, may
      be useful to preserve exposure to surgical procedures.

PMID- 21719513
TI  - Found in translation: Crossing the corpus callosum to explain science.

PMID- 21719512
TI  - Focal adhesions and Ras are functionally and spatially integrated to mediate IL-1
      activation of ERK.
AB  - In connective tissue cells, IL-1-induced ERK activation leading to matrix
      metalloproteinase (MMP)-3 expression is dependent on cooperative interactions
      between focal adhesions and the endoplasmic reticulum (ER). As Ras can be
      activated on the ER, we investigated the role of Ras in IL-1 signaling and focal
      adhesion formation. We found that constitutively active H-Ras, K-Ras or N-Ras
      enhanced focal adhesion maturation and beta1-integrin activation. IL-1 promoted
      the accumulation of Ras isoforms in ER and focal adhesion fractions, as shown in
      cells cotransfected with GFP-tagged Ras isoforms and YFP-ER protein and by
      analysis of subcellular fractions enriched for ER or focal adhesion proteins.
      Dominant-negative H-Ras or K-Ras reduced accumulation of H-Ras and K-Ras in focal
      adhesions induced by IL-1 and also blocked ERK activation and focal adhesion
      maturation. Ras-GRF was enriched constitutively in focal adhesion fractions and
      was required for Ras recruitment to focal adhesions. We conclude that Ras
      activation and IL-1 signaling are interactive processes that regulate the
      maturation of focal adhesions, which, in turn, is required for ERK activation.

PMID- 21719514
TI  - Emergent pharmacology of conscious experience: new perspectives in substance
      addiction.
AB  - We here review experimental findings relevant for the pharmacology of conscious
      experience, an issue largely neglected in pharmacological research. First, we
      focus on self-awareness, a pivotal component of conscious experience and its
      integration within the global neuronal network (GNW), a theoretical concept that
      unifies convergent approaches on the neural bases of conscious processing. We
      report recent evidence to show that self-awareness mobilizes a paralimbic
      circuitry of gamma synchrony, and that such synchrony is, in particular,
      regulated by GABA interneurons under the control of acetylcholine and dopamine.
      Recent data illustrate that these neurotransmitters establish a causal
      relationship with the control of self-awareness. The hypothesis is presented that
      not only is self-awareness chemically regulated, but the reverse may be true.
      Long-term deficit in self-control of drug intake would result in compulsive
      substance use, accompanied, in particular, with lesions of the paralimbic
      circuitry of self-awareness, leading to aggravation of substance abuse, resulting
      in addiction in a vicious circle. Finally, we propose that the emergent
      pharmacology of conscious experience may provide new perspectives, not only in
      substance addiction but also in the many other pathological conditions with
      deficient self-awareness.

PMID- 21719515
TI  - Stigmatization of 'psychiatric label' by medical and non-medical students.
AB  - BACKGROUND: Stigmatization of psychiatric patients is present both in the general
      population and among healthcare professionals. AIM: To determine the attitudes
      and behaviour of medical students towards a person who goes to a psychiatrist,
      before and after psychiatric rotation, and to compare those attitudes between
      medical and non-medical students. METHODS: The study included 525 medical
      students (second and sixth year of studies) and 154 students of law. The study
      instrument was a three-part self-reported questionnaire (socio-demographic data,
      Rosenberg Self-Esteem Scale and a vignette depicting a young, mentally healthy
      person). The experimental intervention consisted of ascribing a 'psychiatric
      label' to only one set of vignettes. All the vignettes (with or without the
      'psychiatric label') were followed by 14 statements addressing the acceptance of
      a person described by vignette, as judged by social distance (four-point Likert
      scale). RESULTS: Higher tendency to stigmatize was found in medical students in
      the final year, after psychiatric rotation (Z(U) = -3.12, p = .002), particularly
      in a closer relationship (Z(U) = -2.67, p = .007) between a student and a
      hypothetical person who goes to a psychiatrist. The non-medical students had a
      similar tendency to stigmatize as medical students before psychiatric rotation
      (Z(U) = -0.03, p = .975). Neither gender, nor the size of student's place of
      origin or average academic mark was associated with the tendency to stigmatize in
      our sample. However, student's elf-esteem was lower in those with a tendency to
      stigmatize more in a distant relationship (rho = -0.157, p = .005). CONCLUSIONS:
      Psychiatric education can either reinforce stigmatization or reduce it.
      Therefore, detailed analyses of educational domains that reinforce stigma will be
      the starting point for anti-stigma action.

PMID- 21719516
TI  - Intramuscular ganglion of the thenar muscles in a 3-year-old girl.

PMID- 21719517
TI  - Progressive median neuropathy caused by the proximal migration of a retained
      foreign body (a glass splinter).

PMID- 21719518
TI  - Complex regional pain syndrome type I as a consequence of trauma or surgery to
      upper extremity: management with intravenous regional anaesthesia, using
      lidocaine and methyloprednisolone.
AB  - Complex regional pain syndrome type I (CRPS-I) is a known complication after
      surgery or trauma to the upper extremity and is difficult to treat. A simple and
      easily tolerated method of treatment that includes intravenous regional
      anaesthetic block with lidocaine and methyloprednisolone is presented. One
      hundred and sixty-eight patients with CRPS-I of the upper extremity were treated
      in a 5-year period. At the end of treatment 88% of the patients reported minimal
      or no pain. After a mean follow-up of 5 years (range 28 months to 7 years)
      complete absence of pain was reported by 92% of patients. The symptoms of the
      acute phase of the syndrome were reversed. Early recognition and prompt
      initiation of treatment is very important for the course of the disease as
      symptoms can be reversible when treatment starts early. Permanent results with a
      functional upper extremity and very satisfactory pain relief can be anticipated.

PMID- 21719519
TI  - A safety device to prevent injury from Kirschner wires.

PMID- 21719520
TI  - Irreducible dorsal fracture dislocation of proximal interphalangeal joint locking
      by the intra-articular avulsion fracture of volar plate from its proximal origin
      at proximal phalanx: case report.

PMID- 21719521
TI  - Rheumatoid hand surgery: differing perceptions amongst surgeons, rheumatologists
      and therapists in the UK.
AB  - Rheumatoid arthritis is a systemic disease that requires coordinated management
      by rheumatologists, surgical specialists and therapists working in a
      multidisciplinary team. Differences of opinion within the team may adversely
      affect patient care. Our aim was to assess differences in perception about
      rheumatoid hand surgery between rheumatologists, hand surgeons and hand
      therapists in the UK. We used a postal questionnaire to assess commonly performed
      rheumatoid hand operations. For each procedure, respondents rated the most
      important indication for surgery and scored effectiveness at reducing pain,
      improving function and aesthetics, and preventing deformity. Statistically
      significant differences were found between all three groups with regards to
      expected outcome and main indications for surgery. We concluded that significant
      differences do exist in the perceptions of rheumatologists, surgeons and
      therapists. Rheumatoid hand operations require more detailed study, clarifying
      indications and outcome to allow consistent advice to patients from all members
      of the multidisciplinary team.

PMID- 21719522
TI  - An unusual suicide attempt with injection of paint thinner in the dorsum of the
      hand.

PMID- 21719523
TI  - Is ultrasound indicated in the diagnosis of closed avulsion injuries of the
      flexor digitorum profundus tendon?

PMID- 21719524
TI  - Gene transfer of angiotensin-converting enzyme 2 in the nucleus tractus
      solitarius improves baroreceptor heart rate reflex in spontaneously hypertensive
      rats.
AB  - The renin-angiotensin system (RAS) in the nucleus tractus solitarius (NTS) is an
      important modulator of the baroreceptor heart rate reflex. This study tested the
      hypothesis that angiotensin-converting enzyme 2 (ACE2) expression is decreased in
      the NTS of spontaneously hypertensive rats (SHRs) and that its gene transfer in
      this nucleus would lead to beneficial effects on baroreflex function since this
      enzyme is key in the regulation of the vasoprotective axis of the RAS. ACE2
      protein levels and its activity were significantly decreased in the NTS of SHRs
      compared to normotensive Wistar-Kyoto (WKY) control rats. Rats instrumented with
      radio-telemetry transducers received NTS microinjection of either Lenti-ACE2
      (Lentiviral vector-mediated gene transfer of ACE2) or lenti-GFP (green
      fluorescent protein). The ACE2 gene transfer into the NTS resulted in long-term
      overexpression of ACE2. This was associated with a 60% increase in heart rate
      baroreflex sensitivity in the lenti-ACE2 injected SHRs compared with the lenti
      GFP injected control SHRs (0.27 +/- 0.02 ms/mmHg in lenti-GFP rats vs. 0.44 +/-
      0.07 ms/mmHg in lenti-ACE2 rats). These observations demonstrate that ACE2 gene
      transfer overcomes its intrinsic decrease in the NTS of SHRs and improves
      baroreceptor heart rate reflex.

PMID- 21719525
TI  - Role of fibrinolytic parameters and plasminogen activator inhibitor 1 (PAI-1)
      promoter polymorphism on premature atherosclerosis in SLE patients.
AB  - Premature atherosclerosis has been recognized as a major co-morbid condition in
      systemic lupus erythematosus (SLE). In this study, we aimed to investigate the
      effect of tPA (tissue plasminogen activator) and PAI-1 (plasminogen activator
      inhibitor) antigen concentrations and 4G/5G polymorphism of the PAI-1 gene on the
      development of atherosclerosis in SLE patients. One hundred and six SLE patients,
      28 Takayasu arteritis (TA) patients and 98 healthy control subjects (HCs) were
      studied. PAI-1 and tPA antigen levels were measured by ELISA method. PAI-1 gene
      polymorphism was determined by using allele-specific PCR method. SLE patients had
      a significantly higher frequency (22.6%) of plaque (p = 0.01) and higher IMT
      (p=0.04) compared with HCs respectively. Only age at disease onset was associated
      with plaque formation in multivariate regression analysis (p = 0.001). Plasma tPA
      ag levels in SLE patients were significantly higher compared with HCs (p = 0.005)
      and PAI-1 ag levels were significantly higher compared with TA patients (p =
      0.03). There were no significant differences between study groups in both
      genotype distribution and allele frequencies of PAI-1 gene, but SLE patients with
      4G/4G genotype had higher IMT (p = 0.02) calcium scoring (p = 0.006) compared
      with 4G5G/5G5G genotypes. The present study suggests that measuring fibrinolytic
      parameters would have little additional benefit beyond traditional and novel risk
      factors in predicting coronary artery disease (CAD).

PMID- 21719526
TI  - The efficacy of romiplostim in the treatment of severe thrombocytopenia
      associated to Evans syndrome refractory to rituximab.
AB  - We present a case of a man diagnosed with systemic lupus erythematosus,
      associated antiphospholipid syndrome and Evans syndrome, who developed a severe
      thrombocytopenia refractory to treatment with first-line drugs, cyclophosphamide
      and rituximab, and who responded to romiplostim with a normalization of the
      platelet recount, which later enabled a therapeutic splenectomy to be performed.

PMID- 21719527
TI  - Age- and gender-related long-term renal outcome in patients with lupus nephritis.
AB  - OBJECTIVE: To investigate age- and gender-related long-term renal outcome in
      patients with lupus nephritis (LN). METHODS: This is a retrospective, chart
      review study of patients with LN at Chang Gung Memorial Hospital, Kaohsiung,
      between January 1986 and June 2004. All had undergone a renal biopsy that showed
      LN. The end point of outcome was chronic renal insufficiency (CRI), which was
      defined as 'doubling of baseline serum creatinine lasting for at least 6 months
      with a value at least 2  mg/dl.' The patients were categorized by age tertiles
      and gender. A 5-year survival curve was constructed to study the effect of age
      and gender on the outcome. RESULTS: In total, 121 sets of patient data were
      evaluated. The study group included 104 women and 17 men. Of the study patients,
      26 (21%) developed CRI after 5 years of follow-up. There was no significant
      difference among age groups in developing CRI (p = 0.23). In terms of gender, men
      had worse long-term renal outcome (p = 0.004) than women. CONCLUSIONS: The long
      term renal outcome of the LN patients did not differ among age groups, but was
      worse in men.

PMID- 21719528
TI  - Maternal and umbilical artery cortisol at birth: relationships with epidural
      analgesia and newborn alertness.
AB  - BACKGROUND: Newborn alertness soon after birth facilitates mother-infant
      interaction and may be related to umbilical cortisol levels. Yet, little is known
      about whether epidural analgesia influences umbilical cortisol at birth. AIM: The
      aims of this study were to explore relationships between exposure to epidural
      analgesia and maternal and umbilical cortisol; maternal and umbilical cortisol
      levels at birth; and umbilical cortisol and infant alertness after birth. METHOD:
      Forty women were self-selected to unmedicated or epidural labors in this pilot
      study. Maternal saliva and infant umbilical artery (UA) plasma at birth were
      enzyme immunoassayed for cortisol. Infant alertness was assessed nearly 1 hr
      after birth. RESULTS: Maternal cortisol was higher in the unmedicated versus
      epidural group (p = .003). Umbilical cortisol was not related to epidural
      analgesia exposure but was related to duration of labor (higher cortisol with
      longer labors; p = .026). Maternal cortisol level explained 55% of the variance
      in umbilical cortisol in the unmedicated group (p = .002), but there was no
      significant shared variance in the epidural sample (p = .776). There was a
      positive correlation (r(2) = .17, p = .008) between umbilical cortisol and infant
      alertness. Latina infants demonstrated a higher frequency of alertness than Black
      infants. In multivariate analysis, umbilical cortisol (p = .049) and
      race/ethnicity (p = .024) remained significant predictors of infant alertness.
      CONCLUSIONS: Our findings indicate that higher umbilical cortisol is related to
      greater infant alertness soon after birth. While epidural analgesia did not
      directly relate to infant cortisol, other factors contributed to higher umbilical
      cortisol.

PMID- 21719529
TI  - Contacts between general practitioners and migrants without a residence permit
      and the use of "urgent" medical care.
AB  - AIMS: To examine the extent to which general practitioners (GPs) are consulted by
      migrants without a residence permit (MRP), their use of the government sponsored
      reimbursement system and the difficulties encountered therewith. To study what
      hurdles the care recipients (MRP) experience in using healthcare and the
      reimbursement system. METHODS: A written survey of GPs in the Brussels Capital
      region and semi-structured interviews with MRP in the same area. Bivariate
      analysis of the GP data (two-sided independent t-test, two-sided Fisher's exact
      test). Recording, transcription, coding and categorizing of MRP interviews.
      RESULTS: Overall GP response rate was 71%. The average number of MRP contacts per
      month was 1.1 for all, representing 0.26% of all GP contacts. GPs working in
      community health centres (CHC) 4.4 MRP per month (p=0.042). The mean probability
      that the GP will not use the reimbursement programme is 0.66--there is less non
      use in CHC (p=0.042). The main barrier for GPs is insufficient knowledge of the
      system, followed by its complex and time consuming paperwork. Barriers
      experienced by MRP include fear of deportation, lack of funds, insufficient
      healthcare related knowledge and communication barriers. CONCLUSIONS: Primary
      care is an active channel in healthcare for MRP, with CHC taking the lead. With
      the reimbursement system, there should hardly be financial barriers to access the
      healthcare system. However, due to the high probability of non-use (0.66), this
      system cannot substantially contribute to lowering financial barriers. The
      complexity of the system prevents it from being used properly and leads to
      undesirable alternatives.

PMID- 21719530
TI  - Active or passive bio-coating: does it matters in extracorporeal circulation?
AB  - BACKGROUND: Two types of surface coating for cardiopulmonary bypass (CPB) are
      used: bioactive (heparin, nitric oxide) and biopassive (albumin,
      polyethyleneoxide (PEO), phosphorylcholine). When haemocompatible coatings are
      combined with the separation of pleuro-pericardial aspiration, attenuation of
      both the coagulation and complement cascades, as well as better platelet
      preservation, has been demonstrated. This study wants to investigate if the
      combination of a bioactive with a biopassive coating (unfractionated heparin
      embedded in a phosphorylcholine matrix) combines the beneficial effects of both
      approaches. MATERIALS AND METHODS: Thirty patients undergoing elective CABG were
      prospectively randomized into two groups of 15 patients. The sole exclusion
      criterion was an ejection fraction of less than 40%. In the control group (PC),
      the whole CPB circuit was coated with phosphorylcholine (PC). In the study group
      (XPC), unfractionated heparin was embedded in the PC matrix of the oxygenator and
      arterial line filter. RESULTS: No differences were found for haemolytic index,
      thrombin-anti-thrombin complex (TAT), IL-6, IL-10 and blood loss. PF4 plasma
      concentration increased from 27.6+/-22.0 IU/mL to 165.7+/-43.9 IU/mL (p<0.001) at
      15 minutes of CPB in the PC and from 16.0+/-9.7 IU/mL to 150.9 +/- 61.3 IU/mL
      (p<0.001) in the XPC group. Terminal complement complex (TCC) increased over time
      in both groups until the end of CPB (Figure 2A). Within each group, TCC
      generation was statistically significantly higher after the release of the aortic
      cross-clamp (p<0.001) and at the end of CPB (p<0.001). Total TCC generation was
      statistically significantly higher in the XPC group compared to the PC group
      (p=0.026). The difference was statistically significant after the release of the
      aortic cross-clamp (p=0.005) and at the end of CPB (p=0.001). CONCLUSIONS: Based
      on our results, there is no additional benefit in combining phosphorylcholine
      with unfractionated heparin in elective patients undergoing coronary artery
      bypass grafting (CABG). Massive haemodilution leads to enhanced complement
      activation.

PMID- 21719531
TI  - Profiling the bronchodilator effects of the novel ultra-long-acting beta2-agonist
      indacaterol against established treatments in chronic obstructive pulmonary
      disease.
AB  - Indacaterol is a novel, inhaled, ultra-long-acting beta(2)-agonist providing 24-h
      bronchodilation with once-daily (od) dosing for maintenance use in patients with
      chronic obstructive pulmonary disease (COPD). This article reviews the
      bronchodilator properties of indacaterol compared with other treatments used in
      COPD. Data from five published placebo-controlled studies were reviewed. Two 14
      day crossover studies, the first comparing indacaterol 300 ug od with salmeterol
      50 ug twice daily (bid), the second comparing indacaterol 150 ug and 300 ug od
      with tiotropium 18 ug od, assessed forced expiratory volume in 1 s (FEV(1)) at 24
      h postdose (trough). Third, a 14-day crossover study evaluated trough FEV(1)
      following indacaterol 300 ug dosed morning or evening compared with salmeterol 50
      ug bid. Fourth, a single-dose study of indacaterol 150 and 300 ug measured FEV(1)
      at 5 min postdose compared with salmeterol/fluticasone 50/500 ug and salbutamol
      200 ug. Finally, data from a 1-year study with indacaterol 300 ug and formoterol
      12 ug bid were examined to determine whether bronchodilation was maintained long
      term. In the first two studies, indacaterol increased trough FEV(1) after 14 days
      by a statistically significant and clinically relevant margin over placebo;
      indacaterol had a greater effect than salmeterol and a similar effect to
      tiotropium. In the third study, indacaterol had the same effect on trough FEV(1)
      whether dosed in the morning or evening. In the fourth study, the onset of the
      bronchodilator effect of indacaterol was similar to that of salbutamol. In the
      fifth study, the bronchodilator effect of indacaterol on trough FEV(1) was
      maintained at a significant and clinically relevant level over 52 weeks, whereas
      the bronchodilator effect of formoterol diminished over time. To conclude,
      indacaterol is a highly effective bronchodilator that is superior to or at least
      as effective as other available long-acting bronchodilators for COPD.

PMID- 21719532
TI  - The cytosolic chaperone Hsc70 promotes traffic to the cell surface of
      intracellular retained melanocortin-4 receptor mutants.
AB  - Inherited modifications in protein structure frequently cause a loss-of-function
      by interfering with protein synthesis, transport, or stability. For the obesity
      linked melanocortin-4 receptor (MC4R) and other G protein-coupled receptors, many
      mutants are intracellular retained. The biogenesis and trafficking of G protein
      coupled receptors are regulated by multiple factors, including molecular
      chaperone networks. Here, we have investigated the ability of the cytosolic
      cognate 70-kDa heat-shock protein (Hsc70) chaperone system to modulate cell
      surface expression of MC4R. Clinically occurring MC4R mutants S58C, P78L, and
      D90N were demonstrated to have reduced trafficking to the plasma membrane and to
      be retained at the endoplasmic reticulum (ER). Analyses by fluorescence recovery
      after photobleaching revealed that the mobility of MC4R mutant protein at the ER
      was reduced, implying protein misfolding. In cells expressing MC4R,
      overexpression of Hsc70 resulted in increased levels of wild-type and mutant
      receptors at the cell surface. MC4R and Hsc70 coimmunoprecipitated, and
      fluorescence recovery after photobleaching analyses showed that increasing
      cellular levels of Hsc70 promoted the mobility of ER retained MC4R. Moreover,
      expression of HSJ1b, a cochaperone that enhances degradation of Hsc70 clients,
      reduced cellular levels of MC4R. Hsp70 and Hsp90 chaperone systems collaborate in
      the cellular processing of clients. For MC4R, inhibition of endogenous Hsp90 by
      geldanamycin reduced receptor levels. By contrast, expression of the Hsp90
      cochaperone Aha1 (activator of Hsp90 ATPase) increased cellular levels of MC4R.
      Finally, we demonstrate that signaling of intracellular retained MC4R mutants is
      increased in cells overexpressing Hsc70. These data indicate that cytosolic
      chaperone systems can facilitate rescue of intracellular retained MC4R by
      improving folding. They also support proteostasis networks as a potential target
      for MC4R-linked obesity.

PMID- 21719533
TI  - PAK1-Nck regulates cyclin D1 promoter activity in response to prolactin.
AB  - Prolactin (PRL) is critical for alveolar proliferation and differentiation in
      normal mammary development and is also implicated in breast cancer. PRL
      influences cell proliferation and growth by altering the expression of cyclin D1.
      Cyclin D1 expression is directly regulated by PRL through the Janus kinase 2
      (JAK2)/signal transducer and activator of transcription 5-mediated
      transcriptional activation of the cyclin D1 promoter. A p21-activated serine
      threonine kinase (PAK)1 has also been implicated in the regulation of cyclin D1
      gene expression. We have previously demonstrated that JAK2 directly
      phosphorylates PAK1 and extend these data here to demonstrate that PAK1 activates
      the cyclin D1 promoter in response to PRL. We show that mutation of PAK1 Tyr 153,
      201, and 285 (sites of JAK2 phosphorylation; PAK1 Y3F) decreases both PAK1
      nuclear translocation in response to PRL and PRL-induced cyclin D1 promoter
      activity by 55%. Mutation of the PAK1 nuclear localization signals decreases PRL
      induced cyclin D1 promoter activity by 46%. A PAK1 Y3F mutant lacking functional
      nuclear localization signals decreases PRL-induced cyclin D1 activity by 68%,
      suggesting that there is another PAK1-dependent mechanism to activate the cyclin
      D1 promoter. We have found that adapter protein Nck sequesters PAK1 in the
      cytoplasm and that coexpression of both PAK1 and Nck inhibits the amplifying
      effect of PRL-induced PAK1 on cyclin D1 promoter activity (95% inhibition). This
      inhibition is partially abolished by disruption of PAK1-Nck binding. We propose
      two PAK1-dependent mechanisms to activate cyclin D1 promoter activity in response
      to PRL: via nuclear translocation of tyrosyl-phosphorylated PAK1 and via
      formation of a Nck-PAK1 complex that sequesters PAK1 in the cytoplasm.

PMID- 21719534
TI  - Leucine deprivation stimulates fat loss via increasing CRH expression in the
      hypothalamus and activating the sympathetic nervous system.
AB  - We previously showed that leucine deprivation decreases abdominal fat mass
      largely by increasing energy expenditure, as demonstrated by increased lipolysis
      in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown
      adipose tissue (BAT). The goal of the present study was to investigate the
      possible involvement of central nervous system (CNS) in this regulation and
      elucidate underlying molecular mechanisms. For this purpose, levels of genes and
      proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in
      wild-type mice after intracerebroventricular administration of leucine or
      corticotrophin-releasing hormone antibodies, or in mice deleted for three beta
      adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d.
      Here, we show that intracerebroventricular administration of leucine
      significantly attenuates abdominal fat loss and blocks activation of hormone
      sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice.
      Furthermore, we provide evidence that leucine deprivation stimulates fat loss by
      increasing expression of corticotrophin-releasing hormone in the hypothalamus via
      activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element
      binding protein pathway. Finally, we show that the effect of leucine deprivation
      on fat loss is mediated by activation of the sympathetic nervous system. These
      results suggest that CNS plays an important role in regulating fat loss under
      leucine deprivation and thereby provide novel and important insights concerning
      the importance of CNS leucine in the regulation of energy homeostasis.

PMID- 21719535
TI  - Ghrelin directly stimulates glucagon secretion from pancreatic alpha-cells.
AB  - Previous work has demonstrated that the peptide hormone ghrelin raises blood
      glucose. Such has been attributed to ghrelin's ability to enhance GH secretion,
      restrict insulin release, and/or reduce insulin sensitivity. Ghrelin's reported
      effects on glucagon have been inconsistent. Here, both animal- and cell-based
      systems were used to determine the role of glucagon in mediating ghrelin's
      effects on blood glucose. The tissue and cell distribution of ghrelin receptors
      (GHSR) was evaluated by quantitative PCR and histochemistry. Plasma glucagon
      levels were determined following acute acyl-ghrelin injections and in
      pharmacological and/or transgenic mouse models of ghrelin overexpression and GHSR
      deletion. Isolated mouse islets and the alpha-cell lines alphaTC1 and InR1G9 were
      used to evaluate ghrelin's effects on glucagon secretion and the role of calcium
      and ERK in this activity. GHSR mRNA was abundantly expressed in mouse islets and
      colocalized with glucagon in alpha-cells. Elevation of acyl-ghrelin acutely
      (after sc administration, such that physiologically relevant plasma ghrelin
      levels were achieved) and chronically (by slow-releasing osmotic pumps and as
      observed in transgenic mice harboring ghrelinomas) led to higher plasma glucagon
      and increased blood glucose. Conversely, genetic GHSR deletion was associated
      with lower plasma glucagon and reduced fasting blood glucose. Acyl-ghrelin
      increased glucagon secretion in a dose-dependent manner from mouse islets and
      alpha-cell lines, in a manner requiring elevation of intracellular calcium and
      phosphorylation of ERK. Our study shows that ghrelin's regulation of blood
      glucose involves direct stimulation of glucagon secretion from alpha-cells and
      introduces the ghrelin-glucagon axis as an important mechanism controlling
      glycemia under fasting conditions.

PMID- 21719536
TI  - Non-coding nucleotides and amino acids near the active site regulate peptide
      deformylase expression and inhibitor susceptibility in Chlamydia trachomatis.
AB  - Chlamydia trachomatis, an obligate intracellular bacterium, is a highly prevalent
      human pathogen. Hydroxamic-acid-based matrix metalloprotease inhibitors can
      effectively inhibit the pathogen both in vitro and in vivo, and have exhibited
      therapeutic potential. Here, we provide genome sequencing data indicating that
      peptide deformylase (PDF) is the sole target of the inhibitors in this organism.
      We further report molecular mechanisms that control chlamydial PDF (cPDF)
      expression and inhibition efficiency. In particular, we identify the sigma66
      dependent promoter that controls cPDF gene expression and demonstrate that point
      mutations in this promoter lead to resistance by increasing cPDF transcription.
      Furthermore, we show that substitution of two amino acids near the active site of
      the enzyme alters enzyme kinetics and protein stability.

PMID- 21719537
TI  - The PmrA/PmrB regulatory system controls the expression of the wzzfepE gene
      involved in the O-antigen synthesis of Salmonella enterica serovar Typhimurium.
AB  - The degree of polymerization of O-antigen from Salmonella enterica serovar
      Typhimurium is controlled by the products of the wzz(s)(t) and wzz(fepE) genes.
      In the present study we investigated the role of the PmrA/PmrB regulatory system
      in wzz(fepE) transcription. We report that the direct binding of the PmrA
      regulator to a specific promoter site induces the expression of the wzz(fepE)
      gene. This effect increases the amount of very long (VL) O-antigen, which is
      required for the resistance of Salmonella to serum human complement and polymyxin
      B, and for the replication of the bacteria within macrophages. The results
      obtained here highlight functional differences between Wzz(fepE) and Wzz(st),
      although the genes for both proteins are regulated in a PmrA-dependent way.

PMID- 21719538
TI  - Disruption of the alsSD operon of Enterococcus faecalis impairs growth on
      pyruvate at low pH.
AB  - Diacetyl and acetoin are pyruvate-derived metabolites excreted by many micro
      organisms, and are important in their physiology. Although generation of these
      four-carbon (C4) compounds in Enterococcus faecalis is a well-documented
      phenotype, little is known about the gene regulation of their biosynthetic
      pathway and the physiological role of the pathway in this bacterium. In this
      work, we identified the genes involved in C4 compound biosynthesis in Ent.
      faecalis and report their transcriptional analysis. These genes are part of the
      alsSD bicistronic operon, which encodes alpha-acetolactate synthase (AlsS) and
      alpha-acetolactate decarboxylase (AlsD). Our studies showed that alsSD operon
      transcription levels are maximal during the exponential phase of growth,
      decreasing thereafter. Furthermore, we found that this transcription is enhanced
      upon addition of pyruvate to the growth medium. In order to study the functional
      role of the alsSD operon, an isogenic alsSD mutant strain was constructed. This
      strain lost its capacity to generate C4 compounds, confirming the role of alsSD
      genes in this metabolic pathway. In contrast to the wild-type strain, the alsSD
      deficient strain was unable to grow in LB medium supplemented with pyruvate at an
      initial pH of 4.5. This dramatic reduction in growth parameters for the mutant
      strain was simultaneously accompanied by the inability to alkalinize the internal
      and external medium under these conditions. In sum, these results suggest that
      the decarboxylation reactions related to the C4 biosynthetic pathway give
      enterococcal cells a competitive advantage during pyruvate metabolism at low pH.

PMID- 21719539
TI  - HXK1 regulates carbon catabolism, sporulation, fumonisin B1 production and
      pathogenesis in Fusarium verticillioides.
AB  - In Fusarium verticillioides, a ubiquitous pathogen of maize, virulence and
      mycotoxigenesis are regulated in response to the types and amounts of
      carbohydrates present in maize kernels. In this study, we investigated the role
      of a putative hexokinase-encoding gene (HXK1) in growth, development and
      pathogenesis. A deletion mutant (Deltahxk1) of HXK1 was not able to grow when
      supplied with fructose as the sole carbon source, and growth was impaired when
      glucose, sucrose or maltotriose was provided. Additionally, the Deltahxk1 mutant
      produced unusual swollen hyphae when provided with fructose, but not glucose, as
      the sole carbon source. Moreover, the Deltahxk1 mutant was impaired in fructose
      uptake, although glucose uptake was unaffected. On maize kernels, the Deltahxk1
      mutant was substantially less virulent than the wild-type, but virulence on maize
      stalks was not impaired, possibly indicating a metabolic response to tissue
      specific differences in plant carbohydrate content. Finally, disruption of HXK1
      had a pronounced effect on fungal metabolites produced during colonization of
      maize kernels; the Deltahxk1 mutant produced approximately 50 % less trehalose
      and 80 % less fumonisin B1 (FB1) than the wild-type. The reduction in trehalose
      biosynthesis likely explains observations of increased sensitivity to osmotic
      stress in the Deltahxk1 mutant. In summary, this study links early events in
      carbohydrate sensing and glycolysis to virulence and secondary metabolism in F.
      verticillioides, and thus provides a new foothold from which the genetic
      regulatory networks that underlie pathogenesis and mycotoxigenesis can be
      unravelled and defined.

PMID- 21719540
TI  - Microbial competition between Bacillus subtilis and Staphylococcus aureus
      monitored by imaging mass spectrometry.
AB  - Microbial competition exists in the general environment, such as soil or aquatic
      habitats, upon or within unicellular or multicellular eukaryotic life forms. The
      molecular actions that govern microbial competition, leading to niche
      establishment and microbial monopolization, remain undetermined. The emerging
      technology of imaging mass spectrometry (IMS) enabled the observation that there
      is directionality in the metabolic output of the organism Bacillus subtilis when
      co-cultured with Staphylococcus aureus. The directionally released antibiotic
      alters S. aureus virulence factor production and colonization. Therefore, IMS
      provides insight into the largely hidden nature of competitive microbial
      encounters and niche establishment, and provides a paradigm for future antibiotic
      discovery.

PMID- 21719541
TI  - Transcriptional regulation of Pseudomonas aeruginosa rhlR: role of the CRP
      orthologue Vfr (virulence factor regulator) and quorum-sensing regulators LasR
      and RhlR.
AB  - The production of many virulence factors by Pseudomonas aeruginosa is regulated
      by the quorum-sensing (QS) response. In this regulatory network LasR and RhlR,
      bound to their corresponding autoinducers, play a central role. The QS response
      has a hierarchical structure: LasR/3O-C12-HSL activates the transcription of
      rhlR, and RhlR/C4-HSL activates the transcription of several genes, including the
      rhlAB operon, which encodes the enzymes responsible for rhamnolipid synthesis.
      The rhlAB operon is located immediately upstream of the rhlR gene. rhlR has four
      transcription start sites, two of which are located in the rhlB coding region.
      Vfr directly activates transcription of lasR, and has been reported to be also
      involved in rhlR expression. The aim of this work was to characterize the details
      of the mechanism of rhlR transcriptional regulation. We show that Vfr directly
      regulates rhlR transcription through its binding to several Vfr-binding sites
      (VBSs) present in the rhlR promoter region, one of which has a negative effect on
      transcription. Two of the VBSs overlap with las boxes where LasR/3O-C12-HSL binds
      to activate rhlR transcription. We also show that rhlR transcription is subject
      to positive-feedback autoregulation through RhlR/C4-HSL activation of the rhlA
      promoter. This positive autoregulation plays a major role in rhlR expression.

PMID- 21719542
TI  - Linear plasmids mobilize linear but not circular chromosomes in Streptomyces:
      support for the 'end first' model of conjugal transfer.
AB  - Gram-positive bacteria of the genus Streptomyces possess linear chromosomes and
      linear plasmids capped by terminal proteins covalently bound to the 5' ends of
      the DNA. The linearity of Streptomyces chromosomes raises the question of how
      they are transferred during conjugation, particularly when the mobilizing
      plasmids are also linear. The classical rolling circle replication model for
      transfer of circular plasmids and chromosomes from an internal origin cannot be
      applied to this situation. Instead it has been proposed that linear Streptomyces
      plasmids mobilize themselves and the linear chromosomes from their telomeres
      using terminal-protein-primed DNA synthesis. In support of this 'end first'
      model, we found that artificially circularized Streptomyces chromosomes could not
      be mobilized by linear plasmids (SLP2 and SCP1), while linear chromosomes could.
      In comparison, a circular plasmid (pIJ303) could mobilize both circular and
      linear chromosomes at the same efficiencies. Interestingly, artificially
      circularized SLP2 exhibited partial self-transfer capability, indicating that,
      being a composite replicon, it may have acquired the additional internal origin
      of transfer from an ancestral circular plasmid during evolution.

PMID- 21719543
TI  - The Dickeya dadantii biofilm matrix consists of cellulose nanofibres, and is an
      emergent property dependent upon the type III secretion system and the cellulose
      synthesis operon.
AB  - Dickeya dadantii is a plant-pathogenic bacterium that produces cellulose
      containing biofilms, called pellicles, at the air-liquid interface of liquid
      cultures. D. dadantii pellicle formation appears to be an emergent property
      dependent upon at least three gene clusters, including cellulose synthesis, type
      III secretion system (T3SS) and flagellar genes. The D. dadantii cellulose
      synthesis operon is homologous to that of Gluconacetobacter xylinus, which is
      used for industrial cellulose production, and the cellulose nanofibres produced
      by D. dadantii were similar in diameter and branching pattern to those produced
      by G. xylinus. Salmonella enterica, an enterobacterium closely related to D.
      dadantii, encodes a second type of cellulose synthesis operon, and it produced
      biofilm strands that differed in width and branching pattern from those of D.
      dadantii and G. xylinus. Unlike any previously described cellulose fibre, the D.
      dadantii cellulose nanofibres were decorated with bead-like structures. Mutation
      of the cellulose synthesis operon genes resulted in loss of cellulose synthesis
      and production of a cellulase-resistant biofilm. Mutation of other genes required
      for pellicle formation, including those encoding FliA (a sigma factor that
      regulates flagella production), HrpL (a sigma factor that regulates the T3SS),
      and AdrA, a GGDEF protein, affected both biofilm and cell morphology. Mutation of
      the cellulose synthase bcsA or of bcsC resulted in decreased accumulation of the
      T3SS-secreted protein HrpN.

PMID- 21719544
TI  - PBP5, PBP6 and DacD play different roles in intrinsic beta-lactam resistance of
      Escherichia coli.
AB  - Escherichia coli PBP5, PBP6 and DacD, encoded by dacA, dacC and dacD,
      respectively, share substantial amino acid identity and together constitute ~50 %
      of the total penicillin-binding proteins of E. coli. PBP5 helps maintain
      intrinsic beta-lactam resistance within the cell. To test if PBP6 and DacD play
      simlar roles, we deleted dacC and dacD individually, and dacC in combination with
      dacA, from E. coli 2443 and compared beta-lactam sensitivity of the mutants and
      the parent strain. beta-Lactam resistance was complemented by wild-type, but not
      dd-carboxypeptidase-deficient PBP5, confirming that enzymic activity of PBP5 is
      essential for beta-lactam resistance. Deletion of dacC and expression of PBP6
      during exponential or stationary phase did not alter beta-lactam resistance of a
      dacA mutant. Expression of DacD during mid-exponential phase partially restored
      beta-lactam resistance of the dacA mutant. Therefore, PBP5 dd-carboxypeptidase
      activity is essential for intrinsic beta-lactam resistance of E. coli and DacD
      can partially compensate for PBP5 in this capacity, whereas PBP6 cannot.

PMID- 21719545
TI  - Functional analysis of the nifQdctA1y4vGHIJ operon of Sinorhizobium fredii strain
      NGR234 using a transposon with a NifA-dependent read-out promoter.
AB  - Rhizobia are a disparate collection of soil bacteria capable of reducing
      atmospheric nitrogen in symbiosis with legumes (Fix phenotype). Synthesis of the
      nitrogenase and its accessory components is under the transcriptional control of
      the key regulator NifA and is generally restricted to the endosymbiotic forms of
      rhizobia known as bacteroids. Amongst studied rhizobia, Sinorhizobium fredii
      strain NGR234 has the remarkable ability to fix nitrogen in association with more
      than 130 species in 73 legume genera that form either determinate, indeterminate
      or aeschynomenoid nodules. Hence, NGR234 is a model organism to study nitrogen
      fixation in association with a variety of legumes. The symbiotic plasmid
      pSfrNGR234a carries more than 50 genes that are under the transcriptional control
      of NifA. To facilitate the functional analysis of NifA-regulated genes a new
      transposable element, TnEKm-PwA, was constructed. This transposon combines the
      advantages of in vitro mutagenesis of cloned DNA fragments with a conditional
      read-out promoter from NGR234 (PwA) that reinitiates NifA-dependent transcription
      downstream of transposition sites. To test the characteristics of the new
      transposon, the nifQdctA1y4vGHIJ operon was mutated using either the Omega
      interposon or TnEKm-PwA. The symbiotic phenotypes on various hosts as well as the
      transcriptional characteristics of these mutants were analysed in detail and
      compared with the ineffective (Fix(-)) phenotype of strain NGRDeltanifA, which
      lacks a functional copy of nifA. De novo transcription from inserted copies of
      TnEKm-PwA inside bacteroids was confirmed by qRT-PCR. Unexpectedly, polar mutants
      in dctA1 and nifQ were Fix(+) on all of the hosts tested, indicating that none of
      the six genes of the nifQ operon of NGR234 is essential for symbiotic nitrogen
      fixation on plants that form nodules of either determinate or indeterminate
      types.

PMID- 21719546
TI  - The comparative myocardial protection by propofol and isoflurane in an in vivo
      model of ischemia reperfusion.
AB  - BACKGROUND: Anesthetic Agents protect the heart from ischemic injury during
      perioperative period. We evaluated the protective effects of 2 anesagents on
      myocardial ischemia -reperfusion injury in rabbit models. METHODS: 58
      anesthetized and mechaniventilated rabbits randomly received isoflurane (ISO) 2%,
      propofol (PRP), or were observed as the control group for 15 minutes. We applied
      vascular tourniquet around the left anterior descending artery (LAD). Myocardium
      was reperfused for 4 hours. Derivative of pressure over time (dP/dT(max)), left
      ventricular pressure (dLVP), isovolumetric relaxation time (Tau), and segment
      shortening (SS) were measured over the ischemic and non-ischemic regions of left
      ventricle (LV). Cardiac troponin I (cTnI), tissue concentrations of tumor
      necrosis factor a (TNFa), myeloperoxidase activity assay (MPO), and tissue
      malonyl dialdehyde (MDA) concentrations were measured as indices of cellular
      injury and inflammatory response. RESULTS: dP/dT(max) values significantly
      decreased during ischemia. Following reperfusion, dP/dT(max), dLVP, and Tau
      remained depressed in the control animals. Both PRP and ISO restored the function
      of the myocardium globally. CONCLUSION: Only ISO improved the recovery of the
      ischemic myocardium during reperfusion. The effects of PRP were global in nature
      and involved compensatory hypercontractile state in nonischemic regions of the
      myocardium. Implication. PRP and ISO protect the heart against an ischemic
      injury, but only ISO preserves the function of the myocardium at the ischemic
      region. The survival rate of the PRP-treated group versus the ISO-treated group
      supports the claim that PRP has smaller contribution to recovery from myocardial
      ischemia.

PMID- 21719547
TI  - Echocardiography in the intensive care unit.
AB  - As ultrasound technology improves and ultrasound availability increases,
      echocardiography utilization is growing within intensive care units. Although not
      replacing the often-needed comprehensive echocardiographic evaluation, limited
      bedside echocardiography promises to provide intensivists with enhanced
      diagnostic ability and improved hemodynamic understanding of individual patients.
      Routine and emergency echocardiography within the intensive care unit focuses on
      identifying and optimizing medically treatable conditions in a timely manner.
      Methods for such goal-directed assessments are presented.

PMID- 21719548
TI  - Drug-eluting stents in the perioperative period: what are the key aspects in
      management?

PMID- 21719549
TI  - Intraoperative transesophageal echocardiography and ventricular assist device
      insertion.
AB  - A decade after cardiac surgery was established, transesophageal echocardiography
      (TEE) was developed and used to evaluate perioperative cardiac performance. It
      has become an invaluable tool to provide real-time information in the cardiac
      operating room. TEE provides practical and useful information prior to insertion
      as well as after placement of the device. Additionally, during episodes of device
      malfunction or hemodynamic instability, TEE can be extremely useful in defining
      the etiology of the problem. As ventricular assist devices (VADs) have undergone
      evolution in design and as more VADs are being implanted, the development of
      specific indications for TEE use during device placement is a relevant issue.
      Formal guidelines for use of TEE during VAD insertion are yet to be adopted or
      implemented, but for now TEE remains an essential tool for managing this patient
      population.

PMID- 21719550
TI  - Association of red blood cell transfusion and postoperative outcomes after
      endovascular aortic repair.
AB  - BACKGROUND: Several studies have documented worse postoperative outcomes in
      patients who received red blood cell (RBC) transfusion perioperatively during
      cardiac surgery or in critical care settings. These findings were attributed to
      activation of the inflammatory response with the release of cytokines and immune
      suppression. The aim of this study was to evaluate the association of RBC
      transfusion on the day of surgery and postoperative outcomes following
      endovascular aortic repair (EVAR). METHODS: A total of 510 patients who underwent
      EVAR from April 2005 to March 2007 were considered for analysis. The exposure of
      interest was whether or not patients receive RBC transfusion on the day of
      surgery. The primary outcome was a composite in-hospital morbidity/mortality
      outcome. The authors assessed the association between RBC transfusion and our
      composite outcome using logistic regression after adjusting for the available
      potential confounders using propensity score matching. RESULTS: Propensity scores
      were estimated for 418 out of the 510 patients; 92 patients were not included
      because of missing data. Propensity matching resulted in 42 successfully matched
      pairs. Median (quartiles) propensity score was 0.46 (0.28, 0.66) for the matched
      patients with transfusion and 0.46 (0.29, 0.61) for the matched patients without
      transfusion (P = .75, Wilcoxon rank sum test). Results of the multivariable model
      developed after propensity score matching suggest that RBC transfusion was not
      significantly associated with experiencing a postoperative complication;
      estimated odds ratio (95% confidence interval) of 2.7 (0.8, 9.0), P = .11.
      CONCLUSION: In this study, RBC transfusion was not independently associated with
      an increased incidence of in-hospital morbidity and mortality after EVAR.

PMID- 21719551
TI  - The use of reverse thermosensitive polymer (LeGoo) for temporary vessel occlusion
      in clampless peripheral vascular surgery.
AB  - INTRODUCTION: There is a need to develop methods of vascular hemostasis, which
      limit vessel trauma. LeGoo is a reverse thermosensitive polymer (poloxamer) which
      is a viscous liquid at room temperature, becoming a firm plug at body
      temperature. We aimed to describe early single center experience in clampless
      peripheral vascular surgery. METHODS: Single surgeon experience using LeGoo
      during peripheral vascular surgery between February and October 2010 was
      analyzed. RESULTS: LeGoo was used in 13 anastomoses in 11 patients. A
      satisfactory bloodless field without the use of conventional occlusion devices
      was achieved in 92% of anastomoses. At a median of 36 weeks follow-up, total
      conduit patency was 91%. CONCLUSIONS: In this small series, LeGoo was seen to be
      safe and effective in the provision of a clamp-free bloodless field in the
      context of peripheral vascular surgery. Prospective comparative study is
      necessary to determine performance against conventional vascular clamps.

PMID- 21719552
TI  - Branched endograft repair of mycotic ascending aortic aneurysm using the snorkel
      technique.
AB  - Mycotic aneurysms are difficult clinical cases that can be approached by several
      methods. Debridement of infected tissue with in situ or extra-anatomic bypass is
      the traditional treatment. In poor operative candidates or reoperative cases,
      endovascular therapies can be an alternative. We present a 9-year-old with an
      ascending aortic mycotic aneurysm temporized with an endovascular repair as a
      bridge to definitive open surgery.

PMID- 21719553
TI  - Radiofrequency ablation of the great saphenous vein: resistive versus segmental
      techniques.

PMID- 21719554
TI  - British Cardiovascular Intervention Society Registry for audit and quality
      assessment of percutaneous coronary interventions in the United Kingdom.
AB  - AIMS: To create an inclusive and accurate registry of all percutaneous coronary
      intervention (PCI) procedures performed in the UK for audit to assess quality of
      care, drive improvements in this care and to provide data for research.
      INTERVENTIONS: Feedback to PCI centres with 'live' online data analysis and
      structured monthly and quarterly reports of PCI activity, including process of
      care measures and assessment of risk-adjusted outcome. Annual national reports
      focused on the structure of the provision of PCI across the UK, the
      appropriateness and process of its delivery and outcomes. SETTING: All hospitals
      performing PCI in the UK. YEARS: 1994 to present. POPULATION: Consecutive
      patients treated by PCI. Approximately 80,000 new procedures each year in recent
      years. STARTPOINTS: All attempts to perform a PCI procedure. This is defined as
      when any coronary device is used to approach, probe or cross one or more coronary
      lesions, with the intention of performing a coronary intervention. BASELINE DATA:
      113 variables defining patient demographic features, indications for PCI,
      procedural details and outcomes up to time of hospital discharge. DATA CAPTURE:
      Data entry into local software systems by caregivers and data clerks, with
      subsequent encryption and internet transfer to central data servers. DATA
      QUALITY: Local validation, range checks and consistency assessments during
      upload. No external validation. Feedback of data completeness to all units.
      ACCESS TO DATA: Available for research by application to British Cardiovascular
      Intervention Society using a data sharing agreement which can be obtained at
      http://www.bcis.org.uk.

PMID- 21719555
TI  - Darbepoetin improves endothelial function and increases circulating endothelial
      progenitor cell number in patients with coronary artery disease.
AB  - BACKGROUND: Atherosclerosis is a progressive disease characterised in part by an
      imbalance of endothelial decline and endothelial repair. Erythropoietin has been
      connected to vasculoprotective effects such as enhanced nitric oxide production
      in endothelial cells and mobilisation of endothelial progenitor cells (EPC).
      OBJECTIVE: To determine the effect of erythropoietin on endothelial function and
      EPC mobilisation in humans with atherosclerosis. DESIGN: A prospective single
      blind monocentric study of 20 patients randomly assigned to the test drug or
      placebo treatment over 4 weeks. METHODS: 20 Patients with stable coronary artery
      disease receiving optimal medical treatment with either weekly subcutaneous
      injections of saline (placebo) or the recombinant erythropoietin darbepoetin (60
      MUg/injection) over 3 consecutive weeks. At the initial and final visits, flow
      mediated dilatation (FMD) was determined by ultrasound. The number of EPC was
      determined as the number of CD34/CD133 positive mononuclear cells in peripheral
      blood. RESULTS: Treatment with darbepoetin resulted in a significantly improved
      FMD in each patient, whereas no difference was seen in placebo-treated patients.
      The FMD of darbepoetin-treated patients increased by 7.5+/-1.64%. Additionally,
      an increase in peripheral blood EPC of 50+/-24% was seen. CONCLUSION: Darbepoetin
      given in addition to optimal medical treatment resulted in a significantly
      improved endothelial function in patients with coronary artery disease,
      indicating a promising new atheroprotective treatment option.

PMID- 21719556
TI  - Long-term clinical outcomes of overlapping heterogeneous drug-eluting stents
      compared with homogeneous drug-eluting stents.
AB  - OBJECTIVES: To evaluate long-term clinical outcomes of overlapping heterogeneous
      drug-eluting stents (DES) compared with homogeneous DES. DESIGN AND SETTING: The
      catholic medical centre coronary intervention database is a multicentre database
      of percutaneous coronary intervention with DES. This database contains data on
      consecutive patients from eight coronary intervention centres in Korea. PATIENTS:
      Overlapping homogeneous DES were used in 940 patients and overlapping
      heterogeneous DES in 140 patients between January 2005 and June 2010.
      INTERVENTION: The study enrolled patients with one-vessel disease treated with
      two overlapping DES in one lesion. MAIN OUTCOME MEASURES: The study end point was
      the occurrence of major adverse cardiac events (MACE), defined as cardiac death,
      myocardial infarction (MI) or target lesion revascularisation (TRL). RESULTS: The
      two patient groups had similar baseline clinical and angiographic
      characteristics. MACE, cardiac death, MI and TRL rates, were not significantly
      different between the homogeneous and heterogeneous DES groups (9.9% vs 11.4%,
      p=0.574; 2.7% vs 3.6%, p=0.578; 1.5% vs 1.4%, p=1.000; 5.7% vs 6.4%, p=0.747,
      respectively). In addition, it was found that overlap with second-generation DES
      may be safe and effective, and the sirolimus-eluting stent (SES)+SES group had
      higher rate of MACE-free survival than the paclitaxel-eluting stent (PES)+PES
      group (p=0.014). CONCLUSIONS: Overlapping heterogeneous DES and overlapping
      homogeneous DES had similar long-term safety and efficacy outcomes.

PMID- 21719557
TI  - The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients
      with heart or renal failure.
AB  - OBJECTIVE: Pro-brain natriuretic peptide (proBNP)-108 and N-terminal proBNP-76
      (NT-BNP) contain seven sites for O-linked oligosaccharide attachment. Currently,
      levels of glycosylated NT-BNP are probably underestimated because it is not
      recognised by one antibody in the sandwich assay system. The pathophysiological
      significance of cardiac and plasma levels of non-glycosylated (nonglyNT-BNP) and
      glycosylated NT-BNP (glyNT-BNP) in heart failure (HF) and chronic renal failure
      (CRF) was investigated. METHODS: Plasma samples from 186 patients with HF and 76
      patients with CRF on haemodialysis were studied, together with 11 atrial tissue
      samples. To measure nonglyNT-BNP and glyNT-BNP, samples were incubated with or
      without deglycosylating enzymes and NT-BNP was measured using Roche Elecsys
      proBNP I. The percentage glyNT-BNP was calculated as glyNT-BNP/(glyNT-BNP +
      nonglyNT-BNP). RESULTS: In HF, plasma BNP, nonglyNT-BNP and glyNT-BNP levels all
      increased with increasing disease severity (New York Heart Association class;
      p<0.0001), though the molar ratio remained constant (molar ratio, BNP:nonglyNT
      BNP:glyNT-BNP = 1:2.4:9.6). Before haemodialysis for CRF, plasma BNP and nonglyNT
      BNP were somewhat elevated, and glyNT-BNP was markedly increased (molar ratio,
      BNP:nonglyNT-BNP:glyNT-BNP = 1:8.5:82). After haemodialysis, plasma BNP, nonglyNT
      BNP, atrial natriuretic protein and cGMP all declined (p<0.0001), but glyNT-BNP
      was unchanged. Notably, the percentage of glyNT-BNP was elevated before
      haemodialysis, and was further increased after haemodialysis (p<0.0001). Atrial
      tissue levels of BNP, nonglyNT-BNP and glyNT-BNP were similar. CONCLUSION: THE
      findings suggest that most endogenous plasma NT-BNP is glycosylated and therefore
      undetectable with the current assay system, and that the relative glycosylation
      level is increased by haemodialysis.

PMID- 21719558
TI  - Smoking cessation medications and cigarettes in Guatemala pharmacies.
AB  - BACKGROUND: Guatemala, a party to the Framework Convention on Tobacco Control
      (FCTC), is obliged to promote the wider availability of smoking cessation
      treatment and to restrict tobacco advertising. Pharmacies are fundamental in
      providing smoking cessation medications but also might increase the availability
      of cigarettes. PURPOSE: To assess availability of cessation medications and
      cigarettes and their corresponding advertising in Guatemala pharmacies. METHODS:
      In Guatemala City a representative sample was selected from a list of registered
      pharmacies classified by type (non-profit, chain, independent). In addition, all
      pharmacies in the neighbouring town of Antigua were included for comparison.
      Trained surveyors used a checklist to characterise each pharmacy with respect to
      availability and advertising of cessation medications and cigarettes. RESULTS: A
      total of 505 pharmacies were evaluated. Cessation medications were available in
      115 (22.8%), while cigarettes were available in 29 (5.7%) pharmacies. When
      available, medications were advertised in 1.7% (2) and cigarettes in 72.4% (21)
      of pharmacies. Chain pharmacies were significantly more likely to sell cessation
      medications and cigarettes, and to advertise cigarettes than were non-profit and
      independent pharmacies. CONCLUSION: Most pharmacies in Guatemala do not stock
      cessation medications or cigarettes. Cigarette advertising was more prevalent
      than advertising for cessation medications. FCTC provisions have not been
      implemented in Guatemala pharmacies.

PMID- 21719559
TI  - Systematic kidney disease management in a population with diabetes mellitus:
      turning the tide of kidney failure.
AB  - PROBLEM: A significant proportion of patients with diabetes mellitus do not get
      the benefit of treatment that would reduce their risk of progressive kidney
      disease and reach a nephrologist once significant loss of kidney function has
      already occurred. DESIGN: Systematic disease management of patients with diabetes
      and kidney disease. SETTING: Diverse population (approximately 800,000) in and
      around Birmingham, West Midlands, UK. KEY MEASURES FOR IMPROVEMENT: Number of
      outpatient appointments, estimated glomerular filtration rate (eGFR) at first
      contact with nephrologist, number of patients starting kidney replacement therapy
      (KRT) and mode of KRT at start. STRATEGY FOR CHANGE: Identification of patients
      with low or deteriorating trend in eGFR from weekly database review, specialist
      diabetes-kidney clinic, self-management of blood pressure and transfer to
      multidisciplinary clinic >12 months before end-stage kidney disease. EFFECTS OF
      CHANGE: New patients increased from 62 in 2003 to 132 in 2010; follow-ups fell
      from 251 to 174. Median eGFR at first clinic visit increased from 28.8
      ml/min/1.73 m(2) (range 6.1-67.0) in 2000/2001 to 35.0 (11.1-147.5) in 2010
      (p<0.006). In 2010, the number of patients starting KRT fell 30% below the
      projected activity using 1993-2003 data as baseline (p<0.003). The proportion
      starting KRT with either a kidney transplant, peritoneal dialysis or
      haemodialysis via an arteriovenous fistula increased from 26% in 2000 to 55% in
      2010. LESSONS LEARNED: Systematic disease management across a large population
      significantly improves patient outcomes, increases the productivity of a
      specialist service and could reduce healthcare costs compared with the current
      model of care.

PMID- 21719560
TI  - Alternatives to potentially inappropriate medications for use in e-prescribing
      software: triggers and treatment algorithms.
AB  - OBJECTIVE: To describe the development of evidence-based electronic prescribing
      (e-prescribing) triggers and treatment algorithms for potentially inappropriate
      medications (PIMs) for older adults. DESIGN: Literature review, expert panel and
      focus group. SETTING: Primary care with access to e-prescribing systems.
      PARTICIPANTS: Primary care physicians using e-prescribing systems receiving
      medication history. INTERVENTIONS: Standardised treatment algorithms for
      clinicians attempting to prescribe PIMs for older patients. MAIN OUTCOME MEASURE:
      Development of 15 treatment algorithms suggesting alternative therapies. RESULTS:
      Evidence-based treatment algorithms were well received by primary care
      physicians. Providing alternatives to PIMs would make it easier for physicians to
      change decisions at the point of prescribing. CONCLUSION: Prospectively
      identifying older persons receiving PIMs or with adherence issues and providing
      feasible interventions may prevent adverse drug events.

PMID- 21719561
TI  - Breast cancer cells proliferation is regulated by tyrosine phosphatase SHP1
      through c-jun N-terminal kinase and cooperative induction of RFX-1 and AP-4
      transcription factors.
AB  - In this study, we show that proliferation of breast cancer cells is suppressed by
      IGF-1-activated JNK MAPK pathway. The molecular mechanism by which c-jun-NH,
      kinase (JNK) activation induces antiproliferative signals in IGF-1-stimulated
      breast cancer cells remains unknown. Tyrosine phosphatase SHP1 is known to
      negatively regulate signal transduction pathways activated by cell surface
      receptors including IGF-1. Moreover, SHP1 transcript and protein levels are
      increased in epithelial tumors. Therefore, we hypothesized that IGF-activated JNK
      induces expression of SHP1 in breast cancer cells. To further clarify the role of
      SHP1 in tumor growth, we correlated the proliferation rates of breast
      adenocarcinoma cells with SHP1 expression and JNK activation. We show that
      proliferation of serum- or IGF-1-stimulated breast adenocarcinoma cells is
      negatively regulated by SHP1 and show for the first time that IGF-1-activated JNK
      induces SHP1 expression in MCF-7 cells used as experimental model. In an attempt
      to understand the mechanism by which serum- or IGF-1-activated JNK induces SHP1
      expression resulting in suppression of cell proliferation, we reveal for the
      first time that in serum- or IGF-1-stimulated breast cancer MCF-7 cells, JNK
      induces SHP1 expression through the binding of AP-4 and RFX-1 transcription
      factors to the epithelial tissue-specific SHP1 promoter. Overall, we show for the
      first time that IGF-1-stimulated proliferation of breast adenocarcinoma cells is
      negatively regulated by SHP1 through activation of JNK.

PMID- 21719562
TI  - Exposure to wood smoke particles produces inflammation in healthy volunteers.
AB  - OBJECTIVES: Human exposure to wood smoke particles (WSP) impacts on human health
      through changes in indoor air quality, exposures from wild fires, burning of
      biomass and air pollution. This investigation tested the postulate that healthy
      volunteers exposed to WSP would demonstrate evidence of both pulmonary and
      systemic inflammation. METHODS: Ten volunteers were exposed to filtered air and,
      3 weeks or more later, WSP. Each exposure included alternating 15 min of exercise
      and 15 min of rest for a total duration of 2 h. Wood smoke was generated by
      heating an oak log on an electric element and then delivered to the exposure
      chamber. Endpoints measured in the volunteers included symptoms, pulmonary
      function tests, measures of heart rate variability and repolarisation, blood
      indices and analysis of cells and fluid obtained during bronchoalveolar lavage.
      RESULTS: Mean particle mass for the 10 exposures to air and WSP was measured
      using the mass of particles collected on filters and found to be below the
      detectable limit and 485+/-84 MUg/m(3), respectively (mean+/-SD). There was no
      change in either symptom prevalence or pulmonary function with exposure to WSP.
      At 20 h after wood smoke exposure, blood tests demonstrated an increased
      percentage of neutrophils, and bronchial and bronchoalveolar lavage revealed a
      neutrophilic influx. CONCLUSIONS: We conclude that exposure of healthy volunteers
      to WSP may be associated with evidence of both systemic and pulmonary
      inflammation.

PMID- 21719563
TI  - The impact of heatwaves on mortality and emergency hospital admissions from non
      external causes in Brisbane, Australia.
AB  - OBJECTIVES: Heatwaves can have significant health consequences resulting in
      increased mortality and morbidity. However, their impact on people living in
      tropical/subtropical regions remains largely unknown. This study assessed the
      impact of heatwaves on mortality and emergency hospital admissions (EHAs) from
      non-external causes (NEC) in Brisbane, a subtropical city in Australia. METHODS:
      We acquired daily data on weather, air pollution and EHAs for patients aged 15
      years and over in Brisbane between January 1996 and December 2005, and on
      mortality between January 1996 and November 2004. A locally derived definition of
      heatwave (daily maximum >=37 degrees C for 2 or more consecutive days) was
      adopted. Case-crossover analyses were used to assess the impact of heatwaves on
      cause-specific mortality and EHAs. RESULTS: During heatwaves, there was a
      statistically significant increase in NEC mortality (OR 1.46; 95% CI 1.21 to
      1.77), cardiovascular mortality (OR 1.89; 95% CI 1.44 to 2.48), diabetes
      mortality in those aged 75+ (OR 9.96; 95% CI 1.02 to 96.85), NEC EHAs (OR 1.15;
      95% CI 1.07 to 1.23) and EHAs from renal diseases (OR 1.41; 95% CI 1.09 to 1.83).
      The elderly were found to be particularly vulnerable to heatwaves (eg, for NEC
      EHAs, OR 1.24 for 65-74-year-olds and 1.39 for those aged 75+). CONCLUSIONS:
      Significant increases in NEC mortality and EHAs were observed during heatwaves in
      Brisbane where people are well accustomed to hot summer weather. The most
      vulnerable were the elderly and people with cardiovascular, renal or diabetic
      disease.

PMID- 21719564
TI  - Duration of anti-tubercular therapy in uveitis associated with latent
      tuberculosis: a case-control study.
AB  - AIM: To study the effect of the duration of anti-tubercular treatment (ATT) on
      the recurrence of uveitis associated with latent tuberculosis (TB). METHODS:
      Retrospective review of all consecutive uveitis patients seen at a single,
      tertiary institution over 9 years with uveitis consistent with TB, positive
      tuberculin skin test with other causes ruled out, and a minimum of 6 months
      follow-up after completion of treatment. Clinical characteristics, treatment
      type, treatment duration and clinical response were recorded. Our main outcome
      measure was the effect of ATT duration on the recurrence of inflammation.
      RESULTS: Of the 182 eligible patients, 46 received ATT of >= 6 month's duration;
      18 patients defaulted and received < 6 months treatment. The patients' mean age
      was 45.3 +/- 13.2 years and most were female (n=118, 57.6%) and of Chinese race
      (n=104, 50.7%). Patients who completed > 9 months ATT were less likely to develop
      recurrence compared with those not treated with ATT (OR 0.09; 95% CI 0.01 to
      0.76; p=0.027), while adjusting for potential confounders such as patient
      demographics, anatomical location of uveitis and corticosteroid therapy.
      CONCLUSION: Patients with uveitis and latent TB treated with ATT of > 9 months
      duration had an 11-fold reduction in the likelihood of recurrence.

PMID- 21719565
TI  - Absence of spontaneous venous pulsations in children with pseudopapilloedema.

PMID- 21719566
TI  - Sector iridectomy of iris melanoma: a novel technique for excising the melanoma
      extraocularly.

PMID- 21719567
TI  - No advanced retinopathy of prematurity stages 4 or 5 in a large high-risk German
      cohort.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) remains a major cause of juvenile
      blindness. As screening recommendations are refined, decreasing gestational age
      (GA) and birth weight (BW) constitute an increasing risk for ROP. This
      retrospective case series reviews the screening results of a very immature cohort
      in Germany. METHODS: We conducted ROP screening according to the German
      guidelines of 1999: all preterm infants with a GA of < 32 weeks and/or a BW of <
      1501 g, or with GA >= 32 weeks and postnatal oxygen treatment for > 3 days, were
      assigned for screening. Dense laser coagulation was performed according to the
      current treatment criteria. RESULTS: All 767 consecutive inborn (patients born at
      the Department of Neonatology, University Hospital of Cologne, Germany) preterm
      infants of a tertiary medical centre of maximum care underwent complete screening
      from 2001 to 2009. The treatment incidence was 7.0%. No preterm infant developed
      stage 4/5 ROP. Mean GA and BW of untreated/treated preterm infants were 28.4/24.6
      weeks and 1109/635 g, respectively. Increasing treatment incidence was associated
      with lower GA, but not with lower BW in logistic regression analysis. CONCLUSION:
      In this very immature high-risk cohort, advanced stages 4 and 5 were avoided
      throughout 9 years of screening. We suggest three factors that contributed to
      this outcome: (1) strict adherence to current ROP screening and treatment
      guidelines; (2) prompt and very dense laser coagulation if necessary; and (3) a
      specialised neonatal intensive care unit with experience of very immature babies.

PMID- 21719568
TI  - Intravitreal bevacizumab for exudative branching vascular networks in polypoidal
      choroidal vasculopathy.
AB  - AIMS: To assess the long-term efficacy of intravitreal bevacizumab for recurrent
      leakage owing to the residual branching vascular networks in polypoidal choroidal
      vasculopathy after photodynamic therapy. METHODS: Forty-five eyes with exudative
      branching vascular networks were treated with intravitreal bevacizumab and
      followed for at least 24 months. Original polypoidal lesions had been treated
      successfully with previous photodynamic therapy in all eyes. The best-corrected
      visual acuity and retinal morphological changes were assessed retrospectively.
      RESULTS: Exudative branching vascular networks were characterised as occult
      choroidal neovascularisation (38 eyes) or classic choroidal neovascularisation (7
      eyes) on fluorescein angiography. Intravitreal bevacizumab maintained or improved
      vision in 38 eyes (84%) over 12 months and in 36 eyes (80%) over 24 months,
      although the mean visual acuity at 12 and 24 months did not differ significantly
      compared with baseline. Complete resolution of macular fluid was achieved
      continuously in 26 eyes (58%) during 24 months. Sixteen eyes (36%) responded once
      to treatment but became unresponsive to additional injections for recurrent
      exudation. Three eyes (7%) were refractory to treatment throughout follow-up.
      Cystoid macular oedema eventually developed in 10 eyes and was a poor prognostic
      sign for visual outcome. CONCLUSION: Intravitreal bevacizumab improved the
      retinal morphology and maintained vision over 1 year in most eyes with recurrent
      fluid owing to persistent abnormal vascular networks in polypoidal choroidal
      vasculopathy. The therapeutic response, however, may decrease during the second
      year.

PMID- 21719569
TI  - Isoliquiritigenin from licorice root suppressed neovascularisation in
      experimental ocular angiogenesis models.
AB  - AIM: To explore the antiangiogenic property of isoliquiritigenin (ISL) on in vivo
      and in vitro models. DESIGN: Laboratory investigation. METHODS: The effect of ISL
      on angiogenesis development was investigated using ex ovo chick chorioallantoic
      membrane model. Its effect on pathological angiogenesis was examined by (1)
      silver nitrate cauterisation-induced corneal neovascularisation in BALB/c mice,
      followed by topical ISL (0.2-50 MUM) and CD31 immunofluorescence of corneal blood
      vessels; (2) argon laser photocoagulation-induced choroidal neovascularisation in
      C57BL/6 mice, followed by intravitreal ISL (10-200 MUM) and fundus fluorescein
      angiography and immunofluorescence with Griffonia simplicifolia isolectin-B4 (GSA
      I-B4); and (3) oxygen-induced retinopathy in C57BL/6J mice pups, followed by
      intravitreal ISL (1-100 MUM) and GSA I-B4 immunofluorescence. The vascular area
      was quantified and analysed by one-way analysis of variance and Student t test.
      Expression of vascular endothelial growth factor (VEGF) and pigment-epithelium
      derived factor in human umbilical vein endothelial cells was analysed by western
      blotting. RESULTS: Ex ovo chick chorioallantoic membrane assay showed that ISL
      dose-dependently suppressed VEGF-induced vessel growth. In vivo experiments
      illustrated that topical ISL alleviated corneal neovascularisation (IC(50)=7.14
      MUM, day 7) and intravitreal ISL reduced vessel leakage and GSA I-B4-positive
      vascular area in choroidal and retinal neovascularisation. ISL was found to dose
      dependently suppress VEGF and induce pigment epithelium derived factor expression
      in cultured endothelial cells. CONCLUSION: Using various experimental models of
      ocular neovascularisation, the authors have demonstrated that ISL from licorice
      extract has an antiangiogenic effect. The authors' findings suggest that ISL may
      be a potential antiangiogenic molecule in the development of therapy for
      neovascularisation diseases.

PMID- 21719570
TI  - Vitreous levels of soluble vascular endothelial growth factor receptor (VEGFR)-1
      in eyes with vitreoretinal diseases.
AB  - BACKGROUND/AIMS: To determine the vitreous levels of soluble vascular endothelial
      growth factor receptor (sVEGFR)-1 in patients with various vitreoretinal
      diseases, and to investigate its correlation with patients' age and the activity
      of proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluid samples were
      obtained from 187 eyes of 170 patients who underwent vitrectomy for the treatment
      of idiopathic macular hole (MH, n=30), branch retinal vein occlusion (BRVO,
      n=37), central retinal vein occlusion (CRVO, n=27), diabetic macular oedema (DME,
      n=42) and PDR (n=51). The levels of sVEGFR-1 in the vitreous were measured by
      ELISA. RESULTS: The levels of sVEGFR-1 (pg/ml) were not significantly different
      among each disease examined (MH 3900.1 +/- 1188.9, BRVO 3969.7 +/- 1741.6, CRVO
      4897.7 +/- 1717.7, DME 3856.21 +/- 1374.7, PDR 4212.3 +/- 1474.9). There was a
      significant positive correlation between vitreous concentrations of sVEGFR-1 and
      patients' age (r=0.430, p<0.01). The sVEGFR-1 concentration in subjects with
      active PDR was significantly lower than in those with quiescent PDR (p<0.0001),
      even after being adjusted for age (p<0.0001). CONCLUSIONS: Vitreous
      concentrations of sVEGFR-1 increase with advancing age and are associated with
      quiescent rather than active PDR even after adjustment for age.

PMID- 21719571
TI  - The genome of the leaf-cutting ant Acromyrmex echinatior suggests key adaptations
      to advanced social life and fungus farming.
AB  - We present a high-quality (>100* depth) Illumina genome sequence of the leaf
      cutting ant Acromyrmex echinatior, a model species for symbiosis and reproductive
      conflict studies. We compare this genome with three previously sequenced genomes
      of ants from different subfamilies and focus our analyses on aspects of the
      genome likely to be associated with known evolutionary changes. The first is the
      specialized fungal diet of A. echinatior, where we find gene loss in the ant's
      arginine synthesis pathway, loss of detoxification genes, and expansion of a
      group of peptidase proteins. One of these is a unique ant-derived contribution to
      the fecal fluid, which otherwise consists of "garden manuring" fungal enzymes
      that are unaffected by ant digestion. The second is multiple mating of queens and
      ejaculate competition, which may be associated with a greatly expanded nardilysin
      like peptidase gene family. The third is sex determination, where we could
      identify only a single homolog of the feminizer gene. As other ants and the
      honeybee have duplications of this gene, we hypothesize that this may partly
      explain the frequent production of diploid male larvae in A. echinatior. The
      fourth is the evolution of eusociality, where we find a highly conserved ant
      specific profile of neuropeptide genes that may be related to caste
      determination. These first analyses of the A. echinatior genome indicate that
      considerable genetic changes are likely to have accompanied the transition from
      hunter-gathering to agricultural food production 50 million years ago, and the
      transition from single to multiple queen mating 10 million years ago.

PMID- 21719572
TI  - Extensive relationship between antisense transcription and alternative splicing
      in the human genome.
AB  - To analyze the relationship between antisense transcription and alternative
      splicing, we developed a computational approach for the detection of antisense
      correlated exon splicing events using Affymetrix exon array data. Our analysis of
      expression data from 176 lymphoblastoid cell lines revealed that the majority of
      expressed sense-antisense genes exhibited alternative splicing events that were
      correlated to the expression of the antisense gene. Most of these events occurred
      in areas of sense-antisense (SAS) gene overlap, which were significantly enriched
      in both exons and nucleosome occupancy levels relative to nonoverlapping regions
      of the same genes. Nucleosome occupancy was highly correlated with Pol II
      abundance across overlapping regions and with concomitant increases in local
      alternative exon usage. These results are consistent with an antisense
      transcription-mediated mechanism of splicing regulation in normal human cells. A
      comparison of the prevalence of antisense-correlated splicing events between
      individuals of Mormon versus African descent revealed population-specific events
      that may indicate the continued evolution of new SAS loci. Furthermore, the
      presence of antisense transcription was correlated to alternative splicing across
      multiple metazoan species, suggesting that it may be a conserved mechanism
      contributing to splicing regulation.

PMID- 21719573
TI  - Long-distance intercellular connectivity between cardiomyocytes and
      cardiofibroblasts mediated by membrane nanotubes.
AB  - AIMS: Intercellular interactions between cardiomyocytes (CMs) and
      cardiofibroblasts (FBs) are important in the physiological and pathophysiological
      heart. Understanding such interactions is important for developing effective
      heart disease therapies. However, until recently, little has been known about
      these interactions. We aimed to investigate structural and functional connections
      between CMs and FBs that are distinct from gap junctions. METHODS AND RESULTS: By
      membrane dye staining, we observed long, thin membrane nanotubular structures
      containing actin and microtubules that connected neonatal rat ventricular CMs and
      FBs. By single-particle tracking, we observed vehicles moving between CMs and FBs
      within the membrane nanotubes. By dual colour staining, confocal imaging and flow
      cytometry, we observed mitochondria exchange between CMs and FBs in a coculture
      system. By combined atomic force microscopy (AFM) and confocal microscopy, we
      observed calcium signal propagation from AFM-stimulated CM (or FB) to
      unstimulated FB (or CM) via membrane nanotubes. By membrane and cytoskeleton
      staining, we observed similar nanotubular structures in adult mouse heart tissue,
      which suggests their physiological relevance. CONCLUSIONS: As a novel type of CM
      to FB communication, membrane nanotubes observed in vitro and in vivo provide
      structural and functional connectivity between CMs and FBs over long distances.

PMID- 21719574
TI  - Natural products modulate Shigella-host-cell interaction.
AB  - This study focused on identifying possible new options derived from natural
      sources for the treatment of bacterial infections. Several natural products were
      investigated for their potential in modulating Shigella-host-cell interactions.
      The proliferation of Shigella sonnei was effectively inhibited inside HEp-2 cells
      in the presence of 4-methoxycinnamic acid and propolin D. Propolin D also
      significantly reduced the apoptosis of infected macrophage-like U937 cells and
      moderately reduced the secretion of interleukin (IL)-1beta and IL-18, which
      probably resulted from the inhibition of invasion plasmid antigen B secretion by
      this compound. Further characterization showed that propolin D did not prevent
      escape of Shigella from phagocytic vacuoles, as evidenced by actin-based motility
      and by the fact that addition of chloroquine did not further reduce the number of
      intracellular c.f.u. The role of propolin D in modulating autophagy could not be
      established under the experimental conditions used. As these compounds had no
      direct anti-Shigella activity in vitro, it was concluded that these compounds
      modulated Shigella-host-cell interactions by targeting yet-to-be defined
      mechanisms that provide benefits to host cells.

PMID- 21719575
TI  - Colonization of the gut with Gram-negative bacilli, its association with neonatal
      sepsis and its clinical relevance in a developing country.
AB  - This study examined the pattern of colonization of the neonatal gut by aerobic
      Gram-negative bacilli (GNB) and evaluated the association between gut
      colonization and sepsis in the developing world. This deserves attention because
      of the high incidence of sepsis and the differences in hygienic environments in
      developing countries compared with the developed world. The study was carried out
      on neonates in a tertiary-care government hospital. Serial gut samples were
      analysed (gastric aspirates and stool samples) for GNB. Blood samples of cases
      showing clinical signs of sepsis were also analysed for septic screening and
      culture positivity. Antibiograms, serotyping and PFGE were carried out to
      evaluate the relatedness of the gut and blood isolates. A diverse array of GNB
      was isolated from the gut of the neonates, Klebsiella pneumoniae being most
      common, followed by Escherichia coli. The rate of isolation of GNB was
      consistently higher in stool samples compared with gastric aspirate samples.
      Colonization was influenced by a stay in the neonatal intensive care unit and by
      the prolonged use of a feeding tube. GNB were the cause of sepsis in the majority
      of cases, with K. pneumoniae being the most frequently isolated GNB from the
      blood. Acinetobacter baumannii, Escherichia coli, Enterobacter cloacae and
      Burkholderia cepacia were the other GNB recovered from the blood of the neonates.
      Neonates with GNB in the gut had a higher incidence of clinical sepsis than those
      without. In 50 % of cases, the genotypes of the organisms found in the blood were
      indistinguishable from their gut counterpart. These results show that the
      neonatal gut is colonized with a diverse array of GNB, and an association between
      gut colonization and neonatal sepsis was observed.

PMID- 21719576
TI  - Carbapenems: do they have a future?

PMID- 21719577
TI  - Escherichia coli resistant to quinolones in a neonatal unit.

PMID- 21719578
TI  - Redundant role of the cytochrome c-mediated intrinsic apoptotic pathway in
      pancreatic beta-cells.
AB  - Cytochrome c is one of the central mediators of the mitochondrial or the
      intrinsic apoptotic pathway. Mice harboring a 'knock-in' mutation of cytochrome
      c, impairing only its apoptotic function, have permitted studies on the essential
      role of cytochrome c-mediated apoptosis in various tissue homeostasis. To this
      end, we examined the role of cytochrome c in pancreatic beta-cells under
      homeostatic conditions and in diabetes models, including those induced by
      streptozotocin (STZ) and c-Myc. Previous studies have shown that both STZ- and c
      Myc-induced beta-cell apoptosis is mediated through caspase-3 activation;
      however, the precise mechanism in these modes of cell death was not
      characterized. The results of our study show that lack of functional cytochrome c
      does not affect glucose homeostasis or pancreatic beta-cell mass under basal
      conditions. Moreover, the cytochrome c-mediated intrinsic apoptotic pathway is
      required for neither STZ- nor c-Myc-induced beta-cell death. We also observed
      that the extrinsic apoptotic pathway mediated through caspase-8 was not essential
      in c-Myc-induced beta-cell destruction. These findings suggest that cytochrome c
      is not required for STZ-induced beta-cell apoptosis and, together with the
      caspase-8-mediated extrinsic pathway, plays a redundant role in c-Myc-induced
      beta-cell apoptosis.

PMID- 21719580
TI  - Endocrinologists release vitamin D guidelines.

PMID- 21719579
TI  - Different fatty acids inhibit apoB100 secretion by different pathways: unique
      roles for ER stress, ceramide, and autophagy.
AB  - Although short-term incubation of hepatocytes with oleic acid (OA) stimulates
      secretion of apolipoprotein B100 (apoB100), exposure to higher doses of OA for
      longer periods inhibits secretion in association with induction of endoplasmic
      reticulum (ER) stress. Palmitic acid (PA) induces ER stress, but its effects on
      apoB100 secretion are unclear. Docosahexaenoic acid (DHA) inhibits apoB100
      secretion, but its effects on ER stress have not been studied. We compared the
      effects of each of these fatty acids on ER stress and apoB100 secretion in
      McArdle RH7777 (McA) cells: OA and PA induced ER stress and inhibited apoB100
      secretion at higher doses; PA was more potent because it also increased the
      synthesis of ceramide. DHA did not induce ER stress but was the most potent
      inhibitor of apoB100 secretion, acting via stimulation of autophagy. These unique
      effects of each fatty acid were confirmed when they were infused into C57BL6J
      mice. Our results suggest that when both increased hepatic secretion of VLDL
      apoB100 and hepatic steatosis coexist, reducing ER stress might alleviate hepatic
      steatosis but at the expense of increased VLDL secretion. In contrast, increasing
      autophagy might reduce VLDL secretion without causing steatosis.

PMID- 21719581
TI  - Fidaxomicin approved for C. difficile infections.

PMID- 21719583
TI  - Collaborative practice comes to New York, expands in Indiana.

PMID- 21719584
TI  - Intradermal vaccine licensed for 2011-12 flu season.

PMID- 21719586
TI  - Implementation of an individualized argatroban protocol in an academic medical
      center.

PMID- 21719587
TI  - Closing the residency training gap.

PMID- 21719588
TI  - Efficacy and safety of sustained-release niacins.

PMID- 21719589
TI  - Activities of a Clostridium difficile infection reduction team.

PMID- 21719590
TI  - Antioxidant and antiatherogenic effects of pomegranate.

PMID- 21719591
TI  - Pharmacotherapy of fibromyalgia.
AB  - PURPOSE: Published evidence on the pathophysiology, diagnosis, and treatment of
      fibromyalgia is reviewed, with an emphasis on recent clinical trials of various
      pharmacologic agents. SUMMARY: Fibromyalgia affects an estimated 2% of the
      general U.S. population, and its incidence is sevenfold higher among women. The
      diagnostic characteristics of fibromyalgia are chronic widespread pain, thought
      to arise from abnormalities of ascending pain and descending inhibitory sensory
      pathways, and allodynia on palpation of specific tender points. Three medications
      available in the United States are labeled for treatment of fibromyalgia-related
      symptoms: the serotonin- and norepinephrine-reuptake inhibitors duloxetine and
      milnacipran and the alpha(2)-delta ligand pregabalin. Evidence from clinical
      trials indicates that all three drugs can have a significant impact on
      fibromyalgia-related pain; duloxetine and pregabalin have been demonstrated to
      reduce sleep disturbances and improve quality of life (the former also has been
      shown to improve mood), while milnacipran can offer significant benefits in
      reducing fatigue. A growing body of evidence suggests that the best treatment
      approach may involve the use of one or more agents whose mechanisms of action are
      aligned with patient-specific clusters of symptoms. Several other agents have
      been used for fibromyalgia, with mixed results, including tricyclic
      antidepressants, selective serotonin-reuptake inhibitors, opioids, and
      gabapentin. Given the limitations of the evidence from clinical trials to date,
      controlled trials directly comparing different agents are needed to better
      delineate adverse-event risks, cost considerations, and optimal management
      approaches. CONCLUSION: A broad range of drugs has been used to treat
      fibromyalgia. Symptoms, comorbidities, adverse effects, and patient preference
      are important considerations in drug selection.

PMID- 21719592
TI  - Rapid-sequence intubation and the role of the emergency department pharmacist.
AB  - PURPOSE: The pharmacology, pharmacokinetics, safety, and dosing of medications
      used during the pretreatment and paralysis with induction steps of rapid-sequence
      intubation (RSI) and the role of the pharmacist in RSI are reviewed. SUMMARY: RSI
      is a process involving the administration of a sedative induction agent and a
      paralytic agent to facilitate endotracheal intubation. This is a procedure in
      which the emergency department (ED) pharmacist can play an integral role,
      especially in the steps of pretreatment, paralysis with induction, and
      postintubation management. The pretreatment phase occurs three minutes before
      administration of induction and neuromuscular blockers. The purpose of
      pretreatment is to attenuate the pathophysiologic response to laryngoscopy and
      intubation. Three minutes after the pre-treatment agents have been administered,
      paralysis with induction will begin. The purpose of induction is to produce a
      state of general anesthesia, allowing for the administration of paralytics and
      facilitation of ideal intubating conditions. It is advisable for the ED
      pharmacist to be familiar with the steps and medications involved with RSI so
      that appropriate interventions may be made, facilitating both the successful
      intubation and the safety of the patient. The relative chaos that may occur
      during emergent RSI requires the ED pharmacist to have a clearly defined primary
      plan as well as contingency plans to deal with potential complications. Commonly
      used medications during intubation include lidocaine, fentanyl, etomidate,
      midazolam, thiopental, ketamine, succinylcholine, and rocuronium. CONCLUSION: The
      selection of an appropriate sedative and neuromuscular blocker during the
      pretreatment and paralysis with induction steps of RSI can be facilitated by an
      ED pharmacist.

PMID- 21719593
TI  - Comparison of patient assistance program software.
AB  - PURPOSE: The capabilities of available software programs for the management of
      applications to patient assistance programs (PAPs) and associated administrative
      tasks are reported. SUMMARY: Fifteen PAP software programs available at the time
      of data collection (July-September 2010) were identified through an Internet
      search and from e-mailed responses to a listserv request. To supplement and
      confirm the information obtained online, the software makers were contacted;
      additional data were collected through follow-up correspondence. The survey was
      restricted to standalone programs; all manufacturer-provided information was
      assumed to be accurate, and the products were not tested. The 15 software
      products evaluated (11 Web-based and 4 Windows-based programs) offered a wide
      range of capabilities to streamline the PAP application process, such as storage
      of patient and physician profiles, automatic completion of forms with stored
      data, application status tracking, and customized report generation. The Web
      based programs offered some advantages over the Windows-based programs, including
      greater user accessibility and automatic updates. Product pricing varied widely,
      depending on the specific licensing terms. Some manufacturers offered discounts
      to health care organizations participating in the 340B Prime Vendor Program; some
      offered volume discounts. In addition, grant support may be available to help pay
      software licensing costs. CONCLUSION: There are at least 15 software programs for
      streamlining and enhancing the process of PAP application management. No single
      program can meet the needs of every organization; selecting the right product
      demands a close look at the needs of an organization and the features and
      logistics of each program.

PMID- 21719594
TI  - Cost-related nonadherence to prescribed medication therapy among Medicare Part D
      beneficiaries with end-stage renal disease.
AB  - PURPOSE: Medication nonadherence due to cost issues among community-dwelling
      patients with end-stage renal disease (ESRD) enrolled in Medicare prescription
      drug plans was evaluated. METHODS: Demographic and health status data were
      collected on 1329 patients with ESRD enrolled in Medicare Part D prescription
      drug plans who responded to a Centers for Medicare and Medicaid Services consumer
      survey in early 2007. The survey data were assessed for self-reported cost
      related nonadherence (CRN), defined as delaying or not filling a prescription due
      to cost concerns. Multivariate logistic regression analysis was performed to
      evaluate CRN risk relative to patient demographic characteristics, socioeconomic
      status, other chronic conditions, health behaviors, and access to health care
      services. RESULTS: Overall, survey respondents with ESRD were significantly more
      likely than those without ESRD to report CRN in the prior six months (unadjusted
      odds ratio [OR], 2.34; 95% confidence interval [CI], 2.00-2.75). After
      controlling for potential confounding factors such as other chronic conditions,
      the data analysis continued to show a significant association between ESRD and an
      increased risk of CRN (adjusted OR, 1.23; 95% CI, 1.07-1.41). Black race and
      receipt of Medicare Part D Low-Income Subsidy assistance were significant
      independent predictors of CRN for respondents with ESRD. CONCLUSION: In early
      2007, 31% of survey respondents with ESRD enrolled in Medicare Part D drug plans
      reported CRN in the preceding six months. After adjusting for potential
      confounders, respondents with ESRD remained 23% more likely than respondents
      without ESRD to report CRN in the preceding six months.

PMID- 21719595
TI  - Impact of an interchange program to support use of insulin pens.
AB  - PURPOSE: The impact of a hospital initiative to reduce staff needle-stick
      injuries and overall insulin costs by switching from use of insulin vials to use
      of insulin pens for treatment of inpatients was evaluated. METHODS: An
      interchange program entailing a switch from vial-and-syringe insulin
      administration to insulin delivery via prefilled injector pens was implemented at
      a specialty clinic and hospital. Patient and employee incident reports were
      reviewed to identify insulin-related staff needle-stick injuries and to assess
      patient safety indicators during six-month periods before and after
      implementation of the interchange. Pharmaceutical purchasing data were used to
      compare total insulin costs for the two periods. RESULTS: In the six months after
      implementation of the interchange program, nurses treated 2,084 patients with
      subcutaneous insulin products; there was one staff needle-stick injury, compared
      with five injuries during the designated preimplementation period (2,118 patients
      treated). During the six months after the switch to insulin injector pens, there
      were four reports of wrong-drug errors (three errors during dispensing and one
      error during administration to the patient), all involving insulin detemir and
      insulin aspart pens; in addition, there was one reported wrong-time error
      associated with a sliding-scale order for insulin aspart. Total insulin product
      costs for the preimplementation and postimplementation periods were $124,181 and
      $60,655, respectively. CONCLUSION: Using an interchange program to support the
      use of insulin pens at a specialty clinic and hospital provided increased staff
      safety and cost savings.

PMID- 21719596
TI  - A comprehensive functional characterization of BRCA2 variants associated with
      Fanconi anemia using mouse ES cell-based assay.
AB  - Biallelic mutations in the human breast cancer susceptibility gene, BRCA2, are
      associated with Fanconi anemia, implying that some persons who inherit 2
      deleterious variants of BRCA2 are able to survive even though it is well
      established that BRCA2 is indispensable for viability in mice. One such variant,
      IVS7 + 2T > G, results in premature protein truncation because of skipping of
      exon 7. Surprisingly, the persons who are either IVS7 + 2T > G homozygous or
      compound heterozygous are born alive but die of malignancy associated with
      Fanconi anemia. Using a mouse embryonic stem cell-based functional assay, we
      found that the IVS7 + 2T > G allele produces an alternatively spliced transcript
      lacking exons 4-7, encoding an in-frame BRCA2 protein with an internal deletion
      of 105 amino acids (BRCA2(Delta105)). We demonstrate that BRCA2(Delta105) is
      proficient in homologous recombination-mediated DNA repair as measured by
      different functional assays. Evaluation of this transcript in normal and leukemia
      cells suggests that BRCA2(Delta105) may contribute to the viability of persons
      inheriting this mutation. In this study, we have also characterized 5 other BRCA2
      variants and found 3 of these (p.L2510P, p.R2336H, and p.W2626C) to be
      deleterious and 2 (p.I2490T and p.K2729N) probably neutral. Such studies are
      important to understand the functional significance of unclassified BRCA2
      variants.

PMID- 21719597
TI  - Targeting levels or oligomerization of nucleophosmin 1 induces differentiation
      and loss of survival of human AML cells with mutant NPM1.
AB  - Nucleophosmin 1 (NPM1) is an oligomeric, nucleolar phosphoprotein that functions
      as a molecular chaperone for both proteins and nucleic acids. NPM1 is mutated in
      approximately one-third of patients with AML. The mutant NPM1c+ contains a 4-base
      insert that results in extra C-terminal residues encoding a nuclear export
      signal, which causes NPM1c+ to be localized in the cytoplasm. Here, we determined
      the effects of targeting NPM1 in cultured and primary AML cells. Treatment with
      siRNA to NPM1 induced p53 and p21, decreased the percentage of cells in S-phase
      of the cell cycle, as well as induced differentiation of the AML OCI-AML3 cells
      that express both NPMc+ and unmutated NPM1. Notably, knockdown of NPM1 by shRNA
      abolished lethal AML phenotype induced by OCI-AML3 cells in NOD/SCID mice.
      Knockdown of NPM1 also sensitized OCI-AML3 to all-trans retinoic acid (ATRA) and
      cytarabine. Inhibition of NPM1 oligomerization by NSC348884 induced apoptosis and
      sensitized OCI-AML3 and primary AML cells expressing NPM1c+ to ATRA. This effect
      was significantly less in AML cells coexpressing FLT3-ITD, or in AML or normal
      CD34+ progenitor cells expressing wild-type NPM1. Thus, attenuating levels or
      oligomerization of NPM1 selectively induces apoptosis and sensitizes NPM1c+
      expressing AML cells to treatment with ATRA and cytarabine.

PMID- 21719598
TI  - Effects of granulocyte-colony stimulating factor on chromosome aneuploidy and
      replication asynchrony in healthy peripheral blood stem cell donors.
AB  - As peripheral blood has surpassed bone marrow as a predominant source of stem
      cells for transplantation, use of the cytokine granulocyte colony-stimulating
      factor (G-CSF) to mobilize peripheral blood stem cells (PBSCs) is increasing.
      Issues regarding potential genotoxic effects of even short-term, low-dose G-CSF
      treatment for the healthy donors have been raised. To address the question of
      chromosomal instability, we used FISH to evaluate the peripheral blood
      lymphocytes of 22 PBSC donors and 22 matched controls at 5 time points over a 12
      month period. The specimens obtained were a pre-G-CSF, followed by collections at
      the time of PBSC harvest (days 5-7) and at 2, 6, and 12 months after donation.
      Eight additional PBSC donors provided a single sample at 12 months. Nine loci
      (mapped to chromosomes 7, 8, 9, 17, 21, and 22) were evaluated for aneuploidy,
      including 3 mapped to chromosome 7 because of the specific relevance of monosomy
      7. Replication timing was evaluated for chromosome 15 and 17 loci. No evidence
      was found of G-CSF-induced chromosomal instability. This work supports the
      epidemiologic data that have demonstrated no increased risk for hematologic
      malignancies in G-CSF-primed PBSC donors.

PMID- 21719599
TI  - Late MRD response determines relapse risk overall and in subsets of childhood T
      cell ALL: results of the AIEOP-BFM-ALL 2000 study.
AB  - The prognostic value of MRD in large series of childhood T-ALL has not yet been
      established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative
      assessment of MRD for stratification, based on immunoglobulin and TCR gene
      rearrangements as polymerase chain reaction targets: Patients were considered MRD
      standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day
      78 (TP2), analyzed by at least 2 sensitive markers; MRD intermediate risk (MRD
      IR) if positive either at day 33 or 78 and < 10(-3) at day 78; and MRD high risk
      (MRD-HR) if >= 10(-3) at day 78. A total of 464 patients with T-ALL were
      stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7
      year event-free-survival (SE) was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P
      < .001), respectively. Negativity of MRD at TP1 was the most favorable prognostic
      factor. An excellent outcome was also obtained in 32% of patients turning MRD
      negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if
      MRD at TP2 was negative (48% of all patients). MRD >= 10(-3) at TP2 constitutes
      the most important predictive factor for relapse in childhood T-ALL. The study is
      registered at http://www.clinicaltrials.gov; "Combination Chemotherapy Based on
      Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia,"
      protocol identification #NCT00430118 for BFM and #NCT00613457 for AIEOP.

PMID- 21719600
TI  - How I conduct a comprehensive chronic graft-versus-host disease assessment.
AB  - Since the National Institutes of Health Chronic Graft-Versus-Host Disease (cGVHD)
      Consensus Project in 2005, a need has emerged to evaluate cGVHD more
      methodically, not only to make a cGVHD diagnosis, but also to accurately classify
      individual organ and global organ severity, at baseline and in follow-up so that
      subjects participating in clinical trials may reliably be assigned an accurate
      response category irrespective of the evaluator. Even for patients not enrolled
      on a clinical trial, periodic complete cGVHD assessments can allow subtle
      manifestations to be detected, monitored carefully, and/or treated early with the
      goal of hopefully avoiding progression to highly morbid, difficult to treat, and
      quite often irreversible forms of cGVHD. Early feedback has been that the
      National Institutes of Health approach to diagnosis classification, staging, and
      response, as well as other new assessment tools, are too detailed and overly
      complex. This article tries to address many of these issues by describing how I
      conduct a comprehensive cGVHD assessment using a streamlined and reliable method
      that I use regularly within the constraints of a busy clinic.

PMID- 21719601
TI  - Characterization of immunologic properties of a second HLA-A2 epitope from a
      granule protease in CML patients and HLA-A2 transgenic mice.
AB  - The serine proteases, neutrophil elastase (HNE) and proteinase 3 (PR3), are
      aberrantly expressed in human myeloid leukemias. T-cell responses to these
      proteins have been correlated with remission in patients with chronic myeloid
      leukemia (CML). Human PR3/HNE-specific CD8(+) T cells predominantly recognize a
      nonameric HLA-A2-restricted T-cell epitope called PR1 which is conserved in both
      Ags. However, CML patients have CD8(+) T cells in peripheral blood recognizing an
      additional HLA-A2 epitope termed PR2. To assess immunologic properties of these
      Ags, novel recombinant vaccinia viruses (rVV) expressing PR3 and HNE were
      evaluated in HLA-A2 transgenic (Tg) mice (HHDII). Immunization of HHDII mice with
      rVV-PR3 elicited a robust PR3-specific CD8(+) T-cell response dominated by
      recognition of PR2, with minimal recognition of the PR1 epitope. This result was
      unexpected, because the PR2 peptide has been reported to bind poorly to HLA. To
      account for these findings, we proposed that HHDII mice negatively selected PR1
      specific T cells because of the presence of this epitope within murine PR3 and
      HNE, leading to immunodominance of PR2-specific responses. PR2-specific
      splenocytes are cytotoxic to targets expressing naturally processed PR3, though
      PR1-specific splenocytes are not. We conclude that PR2 represents a functional T
      cell epitope recognized in mice and human leukemia patients. These studies are
      registered at www.clinicaltrials.gov as NCT00716911.

PMID- 21719602
TI  - Type I-IFNs control GVHD and GVL responses after transplantation.
AB  - Although the effects of type II-IFN (IFN-gamma) on GVHD and leukemia relapse are
      well studied, the effects of type I-interferon (type I-IFN, IFN-alpha/beta)
      remain unclear. We investigated this using type I-IFN receptor-deficient mice and
      exogenous IFN-alpha administration in established models of GVHD and GVL. Type I
      IFN signaling in host tissue prevented severe colon-targeted GVHD in CD4
      dependent models of GVHD directed toward either major histocompatibility antigens
      or multiple minor histocompatibility antigens. This protection was the result of
      suppression of donor CD4(+) T-cell proliferation and differentiation. Studies in
      chimeric recipients demonstrated this was due to type I-IFN signaling in
      hematopoietic tissue. Consistent with this finding, administration of IFN-alpha
      during conditioning inhibited donor CD4(+) proliferation and differentiation. In
      contrast, CD8-dependent GVHD and GVL effects were enhanced when type I-IFN
      signaling was intact in the host or donor, respectively. This finding reflected
      the ability of type I-IFN to both sensitize host target tissue/leukemia to cell
      mediated cytotoxicity and augment donor CTL function. These data confirm that
      type I-IFN plays an important role in defining the balance of GVHD and GVL
      responses and suggests that administration of the cytokine after BM
      transplantation could be studied prospectively in patients at high risk of
      relapse.

PMID- 21719603
TI  - Soluble IL-2Ralpha facilitates IL-2-mediated immune responses and predicts
      reduced survival in follicular B-cell non-Hodgkin lymphoma.
AB  - Elevated serum levels of the soluble form of IL-2 receptor alpha (sIL-2Ralpha)
      have been correlated with a poor prognosis in a variety of different types of
      cancers. However, its biologic relevance remains unclear and controversial. In
      patients with follicular B-cell non-Hodgkin lymphoma (FL), we observed that serum
      sIL-2Ralpha levels were elevated compared with controls and that elevated sIL
      2Ralpha levels before treatment were associated with a poor outcome. To explore
      the mechanism by which sIL-2Ralpha may contribute to a poor prognosis in FL, we
      determined the effects of sIL-2Ralpha on IL-2 signaling and found that the sIL
      2Ralpha-IL-2 complex promoted T-cell differentiation toward to inhibitory T(reg)
      cells rather than T(H)1 or T(H)17 cells. Shed by activated T cells that express
      membrane-bound IL-2Ralpha, sIL-2Ralpha further enhanced IL-2-mediated
      phosphorylation of Stat5 thereby significantly up-regulating Foxp3 expression in
      CD4(+) T cells. We found that CD4(+) T cells treated with either IL-2 or sIL
      2Ralpha-IL-2 complex, but not with sIL-2Ralpha alone, inhibited the function of
      CD8(+) T cells. Taken together, these results indicate that sIL-2Ralpha actually
      plays an active biologic role in FL by binding IL-2 and promoting IL-2 signaling
      rather than depleting IL-2 and blocking its function.

PMID- 21719604
TI  - KSHV: forgotten but not gone.

PMID- 21719605
TI  - Unlicensed natural born killers.

PMID- 21719606
TI  - Opening new roads for MCPyV.

PMID- 21719607
TI  - Indications for and current results with allogeneic hematopoietic cell
      transplantation in patients with myelofibrosis.

PMID- 21719608
TI  - Challenges and strategies for climate change adaptation among Pacific Island
      nations.
AB  - Few regions of the world are at higher risk for environmental disasters than the
      Pacific Island countries and territories. During 2004 and 2005, the top public
      health leadership from 19 of 22 Pacific Island countries and territories convened
      2 health summits with the goal of developing the world's first comprehensive
      regional strategy for sustainable disaster risk management as applied to public
      health emergencies. These summits followed on the objectives of the 1994 Barbados
      Plan of Action for the Sustainable Development of Small Island Developing States
      and those of the subsequent Yokohama Strategy and Plan of Action for a Safer
      World.   The outputs of the 2004 and 2005 Pacific Health Summits for Sustainable
      Disaster Risk Management provide a detailed description of challenges and
      accomplishments of the Pacific Island health ministries, establish a Pacific plan
      of action based upon the principles of disaster risk management, and provide a
      locally derived, evidence-based approach for many climate change adaptation
      measures related to extreme weather events in the Pacific region. The declaration
      and outputs from these summits are offered here as a guide for developmental and
      humanitarian assistance in the region (and for other small-island developing
      states) and as a means for reducing the risk of adverse health effects resulting
      from climate change.

PMID- 21719609
TI  - Elevated interferon gamma signaling contributes to impaired regeneration in the
      aged liver.
AB  - Our previous study on immune-related changes in the aged liver described immune
      cell infiltration and elevation of inflammation with age. Levels of interferon
      (IFN)-gamma, a known cell cycle inhibitor, were elevated in the aging liver.
      Here, we determine the role played by IFN-gamma in the delayed regenerative
      response observed in the aged livers. We observed elevated IFN signaling in both
      aged hepatocytes and regenerating livers post-partial hepatectomy. In vivo
      deletion of the major IFN-gamma producers-the macrophages and the natural killer
      cells, leads to a reduction in the IFN-gamma levels accompanied with the
      restoration of the DNA synthesis kinetics in the aged livers. Eighteen-month-old
      IFN-gamma-/- mice livers, upon resection, exhibited an earlier entry into the
      cell cycle compared with age-matched controls. Thus, our study strongly suggests
      that an age-related elevation in inflammatory conditions in the liver often
      dubbed as "inflammaging" has a detrimental effect on the regenerative response.

PMID- 21719610
TI  - A frailty-related phenotype before HAART initiation as an independent risk factor
      for AIDS or death after HAART among HIV-infected men.
AB  - BACKGROUND: In the general population, frailty, a late stage of the aging
      process, predicts mortality. We investigated whether manifesting a previously
      defined frailty-related phenotype (FRP) before initiating highly active
      antiretroviral therapy (HAART) affects the likelihood of developing clinical AIDS
      or mortality after HAART initiation. METHODS: Among 596 HIV-infected men in the
      Multicenter AIDS Cohort Study whose date of HAART initiation was known within +/
      6 months and who had an assessable FRP status within 3 years before HAART,
      survival analyses were performed to assess the effect of FRP manifestation on
      clinical AIDS or death after HAART. RESULTS: In men free of AIDS before HAART,
      AIDS or death after HAART occurred in 13/36 (36%) men who exhibited the FRP
      before HAART but only in 69/436 (16%) men who did not (hazard ratio = 2.6; 95%
      confidence interval = 1.4-4.6; p < .01). After adjusting for age, ethnicity,
      education, nadir CD4+ T-cell count, peak HIV viral load, and hemoglobin in the 3
      years before HAART, having the FRP at >25% of visits in the 3 years before HAART
      significantly predicted AIDS or death (adjusted hazard ratio = 3.8; 95%
      confidence interval = 1.9-7.9; p < .01). Results were unchanged when the analysis
      was restricted to the 335 AIDS-free men who were HAART responders, to the 124 men
      who had AIDS at HAART initiation, or to the subsets of men for whom indices of
      liver and kidney function could be taken into account. CONCLUSION: Having a
      persistent frailty-like phenotype before HAART initiation predicted a worse
      prognosis after HAART, independent of known risk factors.

PMID- 21719611
TI  - Aloe vera or resveratrol supplementation in larval diet delays adult aging in the
      fruit fly, Drosophila melanogaster.
AB  - Longevity extension in Drosophila melanogaster by feeding diet supplemented with
      chemicals throughout adulthood can cause harmful side effects. We tested the
      effect of larval diet supplementation with five different concentrations of
      resveratrol and one concentration of Aloe vera extract on the adult longevity of
      short-lived D melanogaster populations. Resveratrol and A vera extract
      supplementation of larval diet extended adult longevity in both the male and
      female flies without reducing fecundity but by efficient reactive oxygen species
      scavenging through increased antioxidant enzymes activity and better
      neuroprotection as indicated by increased locomotor activity in adult males.

PMID- 21719612
TI  - Inflammatory markers and gait speed decline in older adults.
AB  - BACKGROUND: Increased inflammatory activity and gait speed decline are common
      with aging, but the association between the two is not well established. The
      objective of this study was to determine the influence of inflammatory markers,
      interleukin-6 (IL-6), and tumor necrosis factor alpha, on gait speed performance
      and decline in older adults. METHODS: We conducted cross-sectional and
      longitudinal analyses of 333 adults aged 70 and older (61% women) with gait and
      biomarker assessments identified from participants in the Einstein Aging Study, a
      community-based aging study. Gait velocity measured at baseline and annual follow
      up visits (median follow-up 2.3 years) was the main outcome. RESULTS: At
      baseline, higher interleukin-6 levels were associated with slower gait velocity
      (estimate -4.90 cm/s, p = .008). Adjusted for age, gender, education, and medical
      illnesses, a one-unit increase in baseline log IL-6 levels was associated with a
      0.98 cm/s faster gait speed decline per year (p = .002). The results remained
      significant after adjustments for additional potential confounders such as
      physical activity levels, body mass index, and medications. Participants in the
      highest IL-6 quartile had a 1.75 cm/s/year faster decline in gait velocity
      compared with those in the lowest quartile (p = .002). Tumor necrosis factor
      alpha was not associated with gait velocity at cross-section or with gait speed
      decline. CONCLUSIONS: IL-6 levels are associated with gait performance in
      community residing seniors and predicts risk of gait speed decline in aging.

PMID- 21719613
TI  - 68-year-old man with persistent methicillin-resistant Staphylococcus aureus
      bacteremia.

PMID- 21719614
TI  - Albert Sabin--conqueror of poliomyelitis.

PMID- 21719615
TI  - Genome-wide association studies go green: novel and cost-effective opportunities
      for identifying genetic associations.

PMID- 21719616
TI  - Regenerative medicine: on the vanguard of health care.

PMID- 21719617
TI  - The need for randomized trials to prove the safety and efficacy of parachutes,
      bulletproof vests, and percutaneous renal intervention.

PMID- 21719618
TI  - Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral
      neuropathic pain management in patients with inadequate pain response to
      gabapentin: an open-label, randomized, noninferiority comparison.
AB  - OBJECTIVE: To determine whether duloxetine is noninferior to (as good as)
      pregabalin in the treatment of pain associated with diabetic peripheral
      neuropathy. PATIENTS AND METHODS: We performed a 12-week, open-label study of
      patients with diabetic peripheral neuropathic pain who had been treated with
      gabapentin (>= 900 mg/d) and had an inadequate response (defined as a daily pain
      score of >= 4 on a numerical rating scale [0-10 points]). The first patient was
      enrolled on September 28, 2006, and the last patient visit occurred on August 26,
      2009. Patients were randomized to duloxetine monotherapy (n=138), pregabalin
      monotherapy (n=134), or a combination of duloxetine and gabapentin (n=135). The
      primary objective was a noninferiority comparison between duloxetine and
      pregabalin on improvement in the weekly mean of the diary-based daily pain score
      (0- to 10-point scale) at end point. Noninferiority would be declared if the mean
      improvement for duloxetine was no worse than the mean improvement for pregabalin,
      within statistical variability, by a margin of -0.8 unit. RESULTS: The mean
      change in the pain rating at end point was -2.6 for duloxetine and -2.1 for
      pregabalin. The 97.5% lower confidence limit was a -0.05 difference in means,
      establishing noninferiority. As to adverse effects, nausea, insomnia,
      hyperhidrosis, and decreased appetite were more frequent with duloxetine than
      pregabalin; insomnia, more frequent with duloxetine than duloxetine plus
      gabapentin; peripheral edema, more frequent with pregabalin than with duloxetine;
      and nausea, hyperhidrosis, decreased appetite, and vomiting, more frequent with
      duloxetine plus gabapentin than with pregabalin. CONCLUSION: Duloxetine was
      noninferior to pregabalin for the treatment of pain in patients with diabetic
      peripheral neuropathy who had an inadequate pain response to gabapentin. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00385671.

PMID- 21719619
TI  - Predictors of omega-3 index in patients with acute myocardial infarction.
AB  - OBJECTIVE: To identify the patient and dietary characteristics associated with
      low omega-3 levels in patients with acute myocardial infarction (AMI) and
      determine whether these characteristics are useful to identify patients who may
      benefit from omega-3 testing and treatment. PATIENTS AND METHODS: Dietary habits
      of 1487 patients in the 24-center Translational Research Investigating Underlying
      disparities in acute Myocardial infarction Patients' Health status (TRIUMPH)
      registry between April 11, 2005, and September 28, 2007, were assessed by asking
      about the frequency of fast food and nonfried fish consumption. All patients had
      erythrocyte omega-3 index measured at the time of hospital admission for AMI. We
      used multivariable linear regression to identify independent correlates of the
      omega-3 index and modified Poisson regression to predict risk of a low omega-3
      index (<4%). RESULTS: The proportion of patients with a low omega-3 index
      increased with more frequent fast food intake (18.9% for <1 time monthly, 28.6%
      for 1-3 times monthly, 28.8% for 1-2 times weekly, and 37.6% for >= 3 times
      weekly; P<.001). In contrast, a low omega-3 index was less common among patients
      with more frequent fish intake (35.1% for <1 time monthly, 24.9% for 1-3 times
      monthly, 16.1% for 1-2 times weekly, and 21.1% for >= 3 times weekly; P<.001).
      Fish intake, older age, race other than white, and omega-3 supplementation were
      independently associated with a higher omega-3 index, whereas frequent fast food
      intake, smoking, and diabetes mellitus were associated with a lower omega-3
      index. CONCLUSION: Potentially modifiable factors, such as patient-reported fast
      food intake, fish intake, and smoking, are independently associated with the
      omega-3 index in patients with AMI. These characteristics may be useful to
      identify patients who would benefit most from omega-3 supplementation and
      lifestyle modification.

PMID- 21719620
TI  - The science and ethics of induced pluripotency: what will become of embryonic
      stem cells?
AB  - For over a decade, the field of stem cell research has advanced tremendously and
      gained new attention in light of novel insights and emerging developments for
      regenerative medicine. Invariably, multiple considerations come into play, and
      clinicians and researchers must weigh the benefits of certain stem cell platforms
      against the costs they incur. Notably, human embryonic stem (hES) cell research
      has been a source of continued debate, leading to differing policies and
      regulations worldwide. This article briefly reviews current stem cell platforms,
      looking specifically at the two existing pluripotent lines available for
      potential therapeutic applications: hES cells and induced pluripotent stem (iPS)
      cells. We submit iPS technology as a viable and possibly superior alternative for
      future medical and research endeavors as it obviates many ethical and resource
      related concerns posed by hES cells while prospectively matching their potential
      for scientific use. However, while the clinical realities of iPS cells appear
      promising, we must recognize the current limitations of this technology, avoid
      hype, and articulate ethically acceptable medical and scientific goals.

PMID- 21719621
TI  - Atherosclerotic renal artery stenosis--diagnosis and treatment.
AB  - Renal artery stenosis (RAS) is characterized by a heterogeneous group of
      pathophysiologic entities, of which fibromuscular dysplasia and atherosclerotic
      RAS (ARAS) are the most common. Whether and which patients should undergo
      revascularization for ARAS is controversial. The general consensus is that all
      patients with ARAS should receive intensive medical treatment. The latest
      randomized clinical trials have increased confusion regarding recommendations for
      revascularization for ARAS. Although revascularization is not indicated in all
      patients with ARAS, experts agree that it should be considered in some patients,
      especially those with unstable angina, unexplained pulmonary edema, and
      hemodynamically significant ARAS with either worsening renal function or with
      difficult to control hypertension. A search of the literature was performed using
      PubMed and entering the search terms renal artery stenosis, atherosclerotic renal
      artery stenosis, and renal artery stenosis AND hypertension to retrieve the most
      recent publications on diagnosis and treatment of ARAS. In this review, we
      analyze the pathways related to hypertension in ARAS, the optimal invasive and
      noninvasive modalities for evaluating the renal arteries, and the available
      therapies for ARAS and assess future tools and algorithms that may prove useful
      in evaluating patients for renal revascularization therapy.

PMID- 21719622
TI  - 33-year-old man with syncope.

PMID- 21719623
TI  - Antimicrobial prophylaxis in adults.
AB  - Antimicrobial prophylaxis is commonly used by clinicians for the prevention of
      numerous infectious diseases, including herpes simplex infection, rheumatic
      fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated
      urinary tract infections in women, spontaneous bacterial peritonitis in patients
      with cirrhosis, influenza, infective endocarditis, pertussis, and acute
      necrotizing pancreatitis, as well as infections associated with open fractures,
      recent prosthetic joint placement, and bite wounds. Perioperative antimicrobial
      prophylaxis is recommended for various surgical procedures to prevent surgical
      site infections. Optimal antimicrobial agents for prophylaxis should be
      bactericidal, nontoxic, inexpensive, and active against the typical pathogens
      that can cause surgical site infection postoperatively. To maximize its
      effectiveness, intravenous perioperative prophylaxis should be administered
      within 30 to 60 minutes before the surgical incision. Antimicrobial prophylaxis
      should be of short duration to decrease toxicity and antimicrobial resistance and
      to reduce cost.

PMID- 21719624
TI  - Diffuse idiopathic skeletal hyperostosis manifesting as recurrent elbow bursitis.

PMID- 21719625
TI  - Think broad, act lean: implications of residency training and duty hour changes
      on health care costs.

PMID- 21719626
TI  - 2010 duty hour standards: seeing beyond the numeric limits.

PMID- 21719627
TI  - Inconclusive findings on effects of duty hour reduction.

PMID- 21719629
TI  - Resident-directed long-term care: staff provision of choice during morning care.
AB  - PURPOSE: To develop an observational protocol to assess the quality of staff
      resident communication relevant to choice and describe staff-resident
      interactions as preliminary evidence of the usefulness of the tool to assess
      current nursing home practices related to offering choice during morning care
      provision. DESIGN AND METHODS: This study included 73 long-stay residents in 2
      facilities. Research staff conducted observations for 4 consecutive morning hours
      during targeted care activities (transfer out of bed, incontinence, dressing, and
      dining location). Observations were conducted weekly for 12 consecutive weeks.
      Staff-resident interactions were measured related to staff offers of choice and
      residents' responses. RESULTS: Interrater agreement was achieved for measures of
      staff offers of choice (kappa = .83, p < .001), type of choice provided (kappa =
      .75, p < .001), and resident requests related to choice (kappa = .72, p < .001).
      Observations over 2,766 care episodes during 4 aspects of morning care showed
      that staff offered residents choice during 18% of the episodes. Most observations
      (70%) were coded as staff offering "no choice." IMPLICATIONS: Nursing home staff
      can use a simplified version of this standardized observational tool to reliably
      measure staff-resident interactions related to choice during morning care
      provision as a first step toward improving resident-directed care practice.

PMID- 21719630
TI  - Adapting Stanford's Chronic Disease Self-Management Program to Hawaii's
      multicultural population.
AB  - PURPOSE OF THE STUDY: Stanford's Chronic Disease Self-Management Program (CDSMP)
      has been proven to increase patients' ability to manage distress. We describe how
      we replicated CDSMP in Asian and Pacific Islander (API) communities. DESIGN AND
      METHODS: We used the "track changes" tool to deconstruct CDSMP into its various
      components (e.g., recruitment and staffing) and the "adaptation traffic light" to
      identify allowable modifications to the original program. We monitored local
      leaders' fidelity of delivery of CDSMP and tracked participants' attendance,
      satisfaction, and 6-month outcomes. RESULTS: Between July 2007 and February 2010,
      584 completed a CDSMP workshop. Baseline and 6-month data were available for 422
      (72%), including 53 Caucasians, 177 Asians, and 194 Pacific Islanders. All 3
      groups realized significant decreases in social and role activity limitations and
      significant increases in communication with physicians. Asians and Pacific
      Islanders also realized significant increases in self-rated health and time spent
      engaging in stretching/strengthening exercise. Asians also reported significant
      reductions in health distress and self-reported physician visits and increases in
      time spent in aerobic exercise, ability to cope with symptoms, and self-efficacy.
      IMPLICATIONS: Our experience suggests that CDSMP can be modified for increased
      cultural appropriateness for API communities while maintaining the key components
      responsible for behavior change.

PMID- 21719631
TI  - Rurality and nursing home quality: evidence from the 2004 National Nursing Home
      Survey.
AB  - PURPOSE OF THE STUDY: To evaluate the impact of rural geographic location on
      nursing home quality of care in the United States. DESIGN AND METHODS: The study
      used cross-sectional observational design. We obtained resident- and facility
      level data from 12,507 residents in 1,174 nursing homes from the 2004 National
      Nursing Home Survey. We used multilevel regression models to predict risk
      adjusted rates of hospitalization, influenza and pneumococcal vaccination, and
      moderate to severe pain while controlling for resident and facility
      characteristics. RESULTS: Adjusting for covariates, residents in rural facilities
      were more likely to experience hospitalization (odds ratio [OR] = 1.50, 95%
      confidence interval [CI] = 1.16-1.94) and moderate to severe pain (OR = 1.68, 95%
      CI = 1.35-2.09). Significant facility-level predictors of higher quality included
      higher percentage of Medicaid beneficiaries, accreditation status, and special
      care programs. Medicare payment findings were mixed. Significant resident-level
      predictors included dementia diagnosis and being a "long-stay" resident.
      IMPLICATIONS: Rural residents were more likely to reside in facilities without
      accreditations or special care programs, factors that increased their odds of
      receiving poorer quality of care. Policy efforts to enhance Medicare payment
      approaches as well as increase rural facilities' accreditation status and
      provision of special care programs will likely reduce quality of care disparities
      in facilities.

PMID- 21719632
TI  - Top management leadership style and quality of care in nursing homes.
AB  - PURPOSE: The purpose of this study was to examine the association of Nursing Home
      Administrator (NHA) leadership style and Director of Nursing (DON) leadership
      style with quality of care. DESIGN AND METHODS: Leaders were categorized into 4
      groups: consensus managers, consultative autocrats, shareholder managers, or
      autocrats. This leadership style assessment came from primary data collected from
      approximately 4,000 NHAs and DONs that was linked to quality information (i.e.,
      Nursing Home Compare Quality Measures and 5-Star rating scores) and nursing home
      information (i.e., Online Survey, Certification, And Reporting data). RESULTS: A
      consensus manager leadership style has a strong association with better quality.
      Top managers using this style solicit and act upon input from their employees.
      For NHAs exhibiting this leadership style, the coefficients on 5 of the 7 quality
      indicators are statistically significant, and all 7 are significant when the DON
      exhibits this style. When the NHA and DON both have a consensus manager
      leadership style, 6 of the 7 quality indicator coefficients are significantly
      associated with better quality. IMPLICATIONS: The findings indicate that NHA and
      DON leadership style is associated with quality of care. Leadership strategies
      are amenable to change; thus, the findings of this study may be used to develop
      policies for promoting more effective leadership in nursing homes.

PMID- 21719633
TI  - Quantification of wet-work exposure in nurses using a newly developed wet-work
      exposure monitor.
AB  - Occupational contact dermatitis (OCD) is an important work-related disease. A
      major cause of OCD is 'wet work': frequent contact of the skin with water, soap,
      detergents, or occlusive gloves. The German guidance TRGS 401 recommends that the
      duration of wet work (including use of occlusive gloves) should not exceed 2 h
      day(-1) and also the frequency of hand washing or hand disinfection should be
      taken into account. This highlights the need for a reliable method to assess
      duration and frequency of wet work. Recently, a wet-work sampler has been
      developed by the University of Aberdeen. The sampler uses the temperature
      difference (DeltaT) generated by evaporative cooling between two sensors: one
      sensor on the skin and a second one placed 2 mm above the skin. We have evaluated
      the use of this sampler in a healthcare setting, using direct observation as
      reference. Twenty-six nurses wore the sampler on the volar side of the middle
      finger for ~2 h during their regular daily tasks, while being observed by a
      researcher. Sampler results were evaluated using various threshold values for
      DeltaT to identify wet events of the hands. The optimal DeltaT to discern wet and
      dry skin differed considerably between individual nurses. Individual results
      yielded a median sensitivity of 78 and 62% and a median specificity of 79 and 68%
      for indicating wet skin and glove use, respectively. Overall, the sampler was
      moderately accurate for identifying wetness of the skin and less accurate for
      discerning glove use. In conclusion, agreement between observed wet work and
      device-reported wet events in healthcare settings was not high and further
      adaptations and developments may be required.

PMID- 21719634
TI  - Examining positive and negative perceptions of older workers: a meta-analysis.
AB  - OBJECTIVE: This article presents an updated meta-analysis of field and laboratory
      studies that examine the influence of age on a number of evaluative workplace
      outcomes (advancement, selection, general evaluations, interpersonal skills, and
      reliability).  Method. A random effects meta-analytic procedure was used.
      RESULTS: In line with the perspective that perceptions of older workers are
      multidimensional, the observed meta-analytic correlations indicate that age has
      medium-sized negative effects on majority of the outcomes investigated
      (r(advancement) = -.21, r(selection) = -.30, r(general evaluations) = -.24, and
      r(interpersonal skills) = -.23, and a medium-sized positive effect on perceptions
      of reliability (r(reliability) = .31). Additionally, evidence of moderation by
      study design for the selection outcome is presented, such that within-subjects
      designs elicit stronger effects of age than between-subjects designs. 
      Discussion. The present study demonstrates that it is likely that older workers
      are not viewed entirely negatively or entirely positively in the workplace;
      rather, the perceptions of older workers are more are varied, and even positive
      in some cases.

PMID- 21719635
TI  - Physical activity measured by the SenseWear Armband in women with rheumatoid
      arthritis.
AB  - BACKGROUND: Individuals with rheumatoid arthritis (RA) often are sedentary and
      have an increased risk of developing comorbid conditions. Women with RA are more
      likely to experience challenges in maintaining an active lifestyle over their
      life span than men with RA or people who are healthy. As the benefits of physical
      activity (PA) are well known, measuring PA accurately in this population is
      important. OBJECTIVES: The purposes of this study were: (1) to characterize PA as
      measured with the SenseWear Armband (SWA) in women with RA and (2) to determine
      the measurement time frame to obtain consistent estimates of PA and daily energy
      expenditure (EE) in women with RA. DESIGN: This was a cross-sectional study.
      METHODS: Participants wore the SWA for 7 days. Measurements of daily total energy
      expenditure (TEE), physical activity energy expenditure (PAEE) during activities
      at or above 1 metabolic equivalent (MET) level (PAEE>=1MET), PAEE during
      activities at or above 2 METs (PAEE>=2METs), PAEE during activities at or above 3
      METs (PAEE>=3METs), and number of steps were obtained. RESULTS: Fifty-three women
      participated. Complete data were obtained for 47 participants (89%). Daily usage
      of the SWA was 98% of the time (23:31 hours/24 hours). Means (SD) were 2,099
      (340) kcal/d for TEE, 1,050 (331) kcal/d for PAEE>=1MET, 642 (309) kcal/d for
      PAEE>=2METs, 239 (178) kcal/d for PAEE>=3METs, and 7,260 (2,710) for number of
      steps. Results of intraclass correlation coefficient analyses and multiple linear
      regressions indicated that 2 days were needed to reliably estimate TEE; 3 days
      for PAEE>=1MET, PAEE>=2METs, and number of steps; and 4 days for PAEE>=3METs.
      LIMITATIONS: The sample was composed of well-educated women with RA who had mild
      to moderate difficulty performing daily activities. CONCLUSION: The SWA may be
      useful to quantify PA in women with RA and to monitor effectiveness of
      interventions aiming to increase PA levels. Minimizing the number of days
      necessary for data collection will reduce the individual's burden and may improve
      adherence in studies of PA behaviors.

PMID- 21719636
TI  - Pediatric physical therapy in infancy: from nightmare to dream? A two-arm
      randomized trial.
AB  - BACKGROUND: Systematic reviews have suggested that early intervention by means of
      specific motor training programs and general developmental programs in which
      parents learn how to promote infant development may be the most promising ways to
      promote infant motor and cognitive development of infants with or at high risk
      for developmental motor disorders. OBJECTIVE: The purpose of this study was to
      investigate the effects of a recently developed pediatric physical therapy
      intervention program ("Coping With and Caring for Infants With Special Needs"
      [COPCA]) on the development of infants at high risk for developmental disorders
      using a combined approach of a 2-arm randomized trial and process evaluation.
      SETTING: The study was conducted at the University Medical Center Groningen in
      the Netherlands. PARTICIPANTS AND INTERVENTION: Forty-six infants at high risk
      for developmental disorders were randomly assigned to receive COPCA (a family
      centered program) (n=21) or traditional infant physical therapy (TIP) (n=25)
      between 3 to 6 months corrected age (CA). Developmental outcome was assessed by
      blinded assessors at 3, 6, and 18 months CA with a neurological examination, the
      Alberta Infant Motor Scales, the Pediatric Evaluation of Disability Inventory,
      and the Mental Developmental Index (MDI) of the Bayley Scales of Infant
      Development. Contents of the intervention were analyzed by a quantitative video
      analysis of therapy sessions. Quantified physical therapy actions were correlated
      to evaluate associations between intervention and developmental outcome
      components. RESULTS: The trial revealed that developmental outcome in both groups
      was largely identical. Process evaluation showed that typical COPCA actions-(1)
      family involvement and educational actions, (2) application of a wide variation
      in challenging the infant to produce motor behavior by himself or herself and
      allowing the infant to continue this activity, and (3) stimulation of motor
      behavior at the limit of the infant's capabilities-had positive correlations with
      developmental outcome at 18 months CA. The use of handling techniques was
      negatively associated with the Pediatric Evaluation of Disability Inventory
      outcome at 18 months CA. LIMITATIONS: Major limitations were the limited size of
      the groups studied and the differences between the groups in frequency and
      duration of physical therapy sessions. CONCLUSION: Extending the randomized trial
      with process evaluation was needed to obtain insight into associations between
      the components of intervention and developmental outcome. Specific therapist
      behaviors of parent coaching are associated with improved developmental outcome
      measures. Further studies are needed to examine whether these associations are
      caused by therapist behavior or whether therapist behavior is modified by
      children's motor skills.

PMID- 21719637
TI  - Test-retest reliability and minimal detectable change scores for sit-to-stand-to
      sit tests, the six-minute walk test, the one-leg heel-rise test, and handgrip
      strength in people undergoing hemodialysis.
AB  - BACKGROUND: Determining the relative and absolute reliability of outcomes of
      physical performance tests for people undergoing hemodialysis is necessary to
      discriminate between the true effects of exercise interventions and the inherent
      variability of this cohort. OBJECTIVE: The aims of this study were to assess the
      relative reliability of sit-to-stand-to-sit tests (the STS-10, which measures the
      time [in seconds] required to complete 10 full stands from a sitting position,
      and the STS-60, which measures the number of repetitions achieved in 60 seconds),
      the Six-Minute Walk Test (6MWT), the one-leg heel-rise test, and the handgrip
      strength test and to calculate minimal detectable change (MDC) scores in people
      undergoing hemodialysis. DESIGN: This study was a prospective, nonexperimental
      investigation. METHODS: Thirty-nine people undergoing hemodialysis at 2 clinics
      in Spain were contacted. Study participants performed the STS-10 (n=37), the STS
      60 (n=37), and the 6MWT (n=36). At one of the settings, the participants also
      performed the one-leg heel-rise test (n=21) and the handgrip strength test (n=12)
      on both the right and the left sides. Participants attended 2 testing sessions 1
      to 2 weeks apart. RESULTS: High intraclass correlation coefficients (>=.88) were
      found for all tests, suggesting good relative reliability. The MDC scores at 90%
      confidence intervals were as follows: 8.4 seconds for the STS-10, 4 repetitions
      for the STS-60, 66.3 m for the 6MWT, 3.4 kg for handgrip strength (force
      generating capacity), 3.7 repetitions for the one-leg heel-rise test with the
      right leg, and 5.2 repetitions for the one-leg heel-rise test with the left leg.
      Limitations A limited sample of patients was used in this study. CONCLUSIONS: The
      STS-16, STS-60, 6MWT, one-leg heel rise test, and handgrip strength test are
      reliable outcome measures. The MDC scores at 90% confidence intervals for these
      tests will help to determine whether a change is due to error or to an
      intervention.

PMID- 21719638
TI  - Differences between the family-centered "COPCA" program and traditional infant
      physical therapy based on neurodevelopmental treatment principles.
AB  - BACKGROUND: Evidence for effectiveness of pediatric physical therapy in infants
      at high risk for developmental motor disorders is limited. Therefore, "Coping
      With and Caring for Infants With Special Needs" (COPCA), a family-centered, early
      intervention program, was developed. The COPCA program is based on 2 components:
      (1) family involvement and educational parenting and (2) the neuromotor
      principles of the neuronal group selection theory. The COPCA coach uses
      principles of coaching to encourage the family's own capacities for solving
      problems of daily care and incorporating variation, along with trial and error in
      daily activities. OBJECTIVE: The purpose of this study was to evaluate whether
      the content of sessions of the home-based, early intervention COPCA program
      differs from that of traditional infant physical therapy (TIP) sessions, which in
      the Netherlands are largely based on neurodevelopmental treatment. SETTING: The
      study was conducted at the University Medical Center Groningen in the
      Netherlands. DESIGN: A quantitative video analysis of therapy sessions was
      conducted with infants participating in a 2-arm randomized trial. PATIENTS AND
      INTERVENTION: Forty-six infants at high risk for developmental motor disorders
      were randomly assigned to receive COPCA (n=21) or TIP (n=25) between 3 and 6
      months corrected age. Intervention sessions were videotaped at 4 and 6 months
      corrected age and analyzed with a standardized observation protocol for the
      classification of physical therapy actions. Outcome parameters were relative
      amounts of time spent on specific physical therapy actions. RESULTS: The content
      of COPCA and TIP differed substantially. For instance, in TIP sessions, more time
      was spent on facilitation techniques, including handling, than in COPCA sessions
      (29% versus 3%, respectively). During COPCA, more time was spent on family
      coaching and education than during TIP (16% versus 4%, respectively).
      LIMITATIONS: The major limitation of the study was its restriction to the
      Netherlands, implying that findings cannot be generalized automatically to other
      countries. CONCLUSION: The COPCA program differs broadly from TIP as applied in
      the Netherlands. Studies on the effectiveness of this family-centered program are
      needed.

PMID- 21719639
TI  - The SINA E3 ligase OsDIS1 negatively regulates drought response in rice.
AB  - Ubiquitin-regulated protein degradation is a critical regulatory mechanism that
      controls a wide range of biological processes in plants. Here, we report that
      OsDIS1 (for Oryza sativa drought-induced SINA protein 1), a C3HC4 RING finger E3
      ligase, is involved in drought-stress signal transduction in rice (O. sativa).
      The expression of OsDIS1 was up-regulated by drought treatment. In vitro
      ubiquitination assays showed that OsDIS1 possessed E3 ubiquitin ligase activity
      and that the conserved region of the RING finger was required for the activity.
      Transient expression assays in Nicotiana benthamiana leaves and rice protoplasts
      indicated that OsDIS1 was localized predominantly in the nucleus. Overexpression
      of OsDIS1 reduced drought tolerance in transgenic rice plants, while RNA
      interference silencing of OsDIS1 enhanced drought tolerance. Microarray analysis
      revealed that a large number of drought-responsive genes were induced or
      suppressed in the OsDIS1 overexpression plants under normal and drought
      conditions. Yeast two-hybrid screening showed that OsDIS1 interacted with OsNek6
      (for O. sativa NIMA-related kinase 6), a tubulin complex-related serine/threonine
      protein kinase. Coexpression assays in N. benthamiana leaves indicated that
      OsNek6 was degraded by OsDIS1 via the 26S proteasome-dependent pathway and that
      this degradation was abolished by the OsDIS1(H71Y) mutation, which is essential
      for its E3 ligase activity. Together, these results demonstrate that OsDIS1 plays
      a negative role in drought stress tolerance through transcriptional regulation of
      diverse stress-related genes and possibly through posttranslational regulation of
      OsNek6 in rice.

PMID- 21719640
TI  - Friction anisotropy-driven domain imaging on exfoliated monolayer graphene.
AB  - Graphene produced by exfoliation has not been able to provide an ideal graphene
      with performance comparable to that predicted by theory, and structural and/or
      electronic defects have been proposed as one cause of reduced performance. We
      report the observation of domains on exfoliated monolayer graphene that differ by
      their friction characteristics, as measured by friction force microscopy. Angle
      dependent scanning revealed friction anisotropy with a periodicity of 180 degrees
      on each friction domain. The friction anisotropy decreased as the applied load
      increased. We propose that the domains arise from ripple distortions that give
      rise to anisotropic friction in each domain as a result of the anisotropic
      puckering of the graphene.

PMID- 21719641
TI  - Altered telomeres in tumors with ATRX and DAXX mutations.
AB  - The proteins encoded by ATRX and DAXX participate in chromatin remodeling at
      telomeres and other genomic sites. Because inactivating mutations of these genes
      are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the
      telomere status of these tumors. We found that 61% of PanNETs displayed abnormal
      telomeres that are characteristic of a telomerase-independent telomere
      maintenance mechanism termed ALT (alternative lengthening of telomeres). All of
      the PanNETs exhibiting these abnormal telomeres had ATRX or DAXX mutations or
      loss of nuclear ATRX or DAXX protein. ATRX mutations also correlate with abnormal
      telomeres in tumors of the central nervous system. These data suggest that an
      alternative telomere maintenance function may operate in human tumors with
      alterations in the ATRX or DAXX genes.

PMID- 21719642
TI  - Isolation of Succinivibrionaceae implicated in low methane emissions from Tammar
      wallabies.
AB  - The Tammar wallaby (Macropus eugenii) harbors unique gut bacteria and produces
      only one-fifth the amount of methane produced by ruminants per unit of digestible
      energy intake. We have isolated a dominant bacterial species (WG-1) from the
      wallaby microbiota affiliated with the family Succinivibrionaceae and implicated
      in lower methane emissions from starch-containing diets. This was achieved by
      using a partial reconstruction of the bacterium's metabolism from binned
      metagenomic data (nitrogen and carbohydrate utilization pathways and antibiotic
      resistance) to devise cultivation-based strategies that produced axenic WG-1
      cultures. Pure-culture studies confirm that the bacterium is capnophilic and
      produces succinate, further explaining a microbiological basis for lower methane
      emissions from macropodids. This knowledge also provides new strategic targets
      for redirecting fermentation and reducing methane production in livestock.

PMID- 21719643
TI  - Trace metals as biomarkers for eumelanin pigment in the fossil record.
AB  - Well-preserved fossils of pivotal early bird and nonavian theropod species have
      provided unequivocal evidence for feathers and/or downlike integuments. Recent
      studies have reconstructed color on the basis of melanosome structure; however,
      the chemistry of these proposed melanosomes has remained unknown. We applied
      synchrotron x-ray techniques to several fossil and extant organisms, including
      Confuciusornis sanctus, in order to map and characterize possible chemical
      residues of melanin pigments. Results show that trace metals, such as copper, are
      present in fossils as organometallic compounds most likely derived from original
      eumelanin. The distribution of these compounds provides a long-lived biomarker of
      melanin presence and density within a range of fossilized organisms. Metal zoning
      patterns may be preserved long after melanosome structures have been destroyed.

PMID- 21719645
TI  - Medical oncology: the long-awaited prize of recognition.

PMID- 21719644
TI  - Structural basis for tail-anchored membrane protein biogenesis by the Get3
      receptor complex.
AB  - Tail-anchored (TA) proteins are involved in cellular processes including
      trafficking, degradation, and apoptosis. They contain a C-terminal membrane
      anchor and are posttranslationally delivered to the endoplasmic reticulum (ER)
      membrane by the Get3 adenosine triphosphatase interacting with the hetero
      oligomeric Get1/2 receptor. We have determined crystal structures of Get3 in
      complex with the cytosolic domains of Get1 and Get2 in different functional
      states at 3.0, 3.2, and 4.6 angstrom resolution. The structural data, together
      with biochemical experiments, show that Get1 and Get2 use adjacent, partially
      overlapping binding sites and that both can bind simultaneously to Get3. Docking
      to the Get1/2 complex allows for conformational changes in Get3 that are required
      for TA protein insertion. These data suggest a molecular mechanism for nucleotide
      regulated delivery of TA proteins.

PMID- 21719651
TI  - Particle physics. Underground lab would cost U.S. billions.

PMID- 21719646
TI  - AIDS: let science inform policy.

PMID- 21719652
TI  - Social psychology. Antismoking drive tries cigarette ads, in reverse.

PMID- 21719653
TI  - Scientific workforce. Suit seeks redress for a start-up package gone sour.

PMID- 21719654
TI  - Infectious diseases. As E. coli outbreak recedes, new questions come to the fore.

PMID- 21719656
TI  - Science on the shuttle. The highs and lows of shuttle science.

PMID- 21719655
TI  - Science on the shuttle. NASA's busload of science.

PMID- 21719657
TI  - Not-so-sunny outlook for organic photovoltaics.

PMID- 21719658
TI  - Editorial expression of concern.

PMID- 21719660
TI  - An unorthodox approach to forest restoration.

PMID- 21719661
TI  - Comment on "The mechanism for activation of GTP hydrolysis on the ribosome".
AB  - Voorhees et al. (Reports, 5 November 2010, p. 835) determined the structure of
      elongation factor Tu (EF-Tu) and aminoacyl-transfer RNA bound to the ribosome
      with a guanosine triphosphate (GTP) analog. However, their identification of
      histidine-84 of EF-Tu as deprotonating the catalytic water molecule is
      problematic in relation to their atomic structure; the terminal phosphate of GTP
      is more likely to be the proper proton acceptor.

PMID- 21719662
TI  - AIDS. Turning the tide against HIV.

PMID- 21719663
TI  - Cell biology. Fishing in the nuclear pore.

PMID- 21719664
TI  - Virology. Revealing virus-host interplay.

PMID- 21719665
TI  - Applied physics. Knot your simple defect lines?

PMID- 21719666
TI  - Neuroscience. Remember when?

PMID- 21719667
TI  - Chemistry. Electrons in cement.

PMID- 21719668
TI  - Cell biology. Protease sets site-1 on lysosomes.

PMID- 21719669
TI  - A biological screw in a beetle's leg.
AB  - The coxa-trochanteral joints on the legs of the weevil Trigonopterus oblongus
      (Pascoe) work as a biological screw-and-nut system. The apical portions of the
      coxae closely resemble nuts with well-defined inner threads covering 345 degrees
      . The corresponding trochanters have perfectly compatible external spiral threads
      of 410 degrees .

PMID- 21719670
TI  - Probing individual environmental bacteria for viruses by using microfluidic
      digital PCR.
AB  - Viruses may very well be the most abundant biological entities on the planet. Yet
      neither metagenomic studies nor classical phage isolation techniques have shed
      much light on the identity of the hosts of most viruses. We used a microfluidic
      digital polymerase chain reaction (PCR) approach to physically link single
      bacterial cells harvested from a natural environment with a viral marker gene.
      When we implemented this technique on the microbial community residing in the
      termite hindgut, we found genus-wide infection patterns displaying remarkable
      intragenus selectivity. Viral marker allelic diversity revealed restricted mixing
      of alleles between hosts, indicating limited lateral gene transfer of these
      alleles despite host proximity. Our approach does not require culturing hosts or
      viruses and provides a method for examining virus-bacterium interactions in many
      environments.

PMID- 21719671
TI  - Reconfigurable knots and links in chiral nematic colloids.
AB  - Tying knots and linking microscopic loops of polymers, macromolecules, or defect
      lines in complex materials is a challenging task for material scientists. We
      demonstrate the knotting of microscopic topological defect lines in chiral
      nematic liquid-crystal colloids into knots and links of arbitrary complexity by
      using laser tweezers as a micromanipulation tool. All knots and links with up to
      six crossings, including the Hopf link, the Star of David, and the Borromean
      rings, are demonstrated, stabilizing colloidal particles into an unusual soft
      matter. The knots in chiral nematic colloids are classified by the quantized self
      linking number, a direct measure of the geometric, or Berry's, phase. Forming
      arbitrary microscopic knots and links in chiral nematic colloids is a
      demonstration of how relevant the topology can be for the material engineering of
      soft matter.

PMID- 21719672
TI  - Rotary photon drag enhanced by a slow-light medium.
AB  - Transmission through a spinning window slightly rotates the polarization of the
      light, typically by a microradian. It has been predicted that the same mechanism
      should also rotate an image. Because this rotary photon drag has a contribution
      that is inversely proportional to the group velocity, the image rotation is
      expected to increase in a slow-light medium. Using a ruby window under conditions
      for coherent population oscillations, we induced an effective group index of
      about 1 million. The resulting rotation angle was large enough to be observed by
      the eye. This result shows that rotary photon drag applies to images as well as
      polarization. The possibility of switching between different rotation states may
      offer new opportunities for controlled image coding.

PMID- 21719673
TI  - Superelastic effect in polycrystalline ferrous alloys.
AB  - In superelastic alloys, large deformation can revert to a memorized shape after
      removing the stress. However, the stress increases with increasing temperature,
      which limits the practical use over a wide temperature range. Polycrystalline Fe
      Mn-Al-Ni shape memory alloys show a small temperature dependence of the
      superelastic stress because of a small transformation entropy change brought
      about by a magnetic contribution to the Gibbs energies. For one alloy
      composition, the superelastic stress varies by 0.53 megapascal/ degrees C over a
      temperature range from -196 to 240 degrees C.

PMID- 21719674
TI  - Solvated electrons in high-temperature melts and glasses of the room-temperature
      stable electride [Ca24Al28O64]4+.4e-.
AB  - Solvated electrons in alkali metal-ammonia solutions have attracted attention as
      a prototype electronic conductor and chemical reducing agent for over a century.
      However, solvated electrons have not been realized in a high-temperature melt or
      glass of an oxide system to date. We demonstrated the formation of persistent
      solvated electrons in both a high-temperature melt and its glass by using the
      thermally stable electride [Ca(24)Al(28)O(64)](4+).4e(-) (C12A7:e(-)) and
      controlling the partial pressure of oxygen. The electrical and structural
      properties of the resulting melt and glass differ from those of the conventional
      C12A7:O(2-) oxide, exhibiting metallic and hopping conduction, respectively, and
      a glass transition temperature that is ~160 kelvin lower than that of C12A7:O(2-)
      glass. Solvated electrons reside in cage structures in C12A7:e(-) and form a
      diamagnetic paired state.

PMID- 21719675
TI  - Large sulfur isotope fractionation does not require disproportionation.
AB  - The composition of sulfur isotopes in sedimentary sulfides and sulfates traces
      the sulfur cycle throughout Earth's history. In particular, depletions of sulfur
      34 ((34)S) in sulfide relative to sulfate exceeding 47 per mil (0/00) often serve
      as a proxy for the disproportionation of intermediate sulfur species in addition
      to sulfate reduction. Here, we demonstrate that a pure, actively growing culture
      of a marine sulfate-reducing bacterium can deplete (34)S by up to 660/00 during
      sulfate reduction alone and in the absence of an extracellular oxidative sulfur
      cycle. Therefore, similar magnitudes of sulfur isotope fractionation in
      sedimentary rocks do not unambiguously record the presence of other sulfur-based
      metabolisms or the stepwise oxygenation of Earth's surface environment during the
      Proterozoic.

PMID- 21719676
TI  - Formation and spread of aircraft-induced holes in clouds.
AB  - Hole-punch and canal clouds have been observed for more than 50 years, but the
      mechanisms of formation, development, duration, and thus the extent of their
      effect have largely been ignored. The holes have been associated with inadvertent
      seeding of clouds with ice particles generated by aircraft, produced through
      spontaneous freezing of cloud droplets in air cooled as it flows around aircraft
      propeller tips or over jet aircraft wings. Model simulations indicate that the
      growth of the ice particles can induce vertical motions with a duration of 1 hour
      or more, a process that expands the holes and canals in clouds. Global effects
      are minimal, but regionally near major airports, additional precipitation can be
      induced.

PMID- 21719677
TI  - Pattern in escalations in insurgent and terrorist activity.
AB  - In military planning, it is important to be able to estimate not only the number
      of fatalities but how often attacks that result in fatalities will take place. We
      uncovered a simple dynamical pattern that may be used to estimate the escalation
      rate and timing of fatal attacks. The time difference between fatal attacks by
      insurgent groups within individual provinces in both Afghanistan and Iraq, and by
      terrorist groups operating worldwide, gives a potent indicator of the later pace
      of lethal activity.

PMID- 21719678
TI  - Mechanism of RAD51-dependent DNA interstrand cross-link repair.
AB  - DNA interstrand cross-links (ICLs) are toxic DNA lesions whose repair in S phase
      of eukaryotic cells is incompletely understood. In Xenopus egg extracts, ICL
      repair is initiated when two replication forks converge on the lesion. Dual
      incisions then create a DNA double-strand break (DSB) in one sister chromatid,
      whereas lesion bypass restores the other sister. We report that the broken sister
      chromatid is repaired via RAD51-dependent strand invasion into the regenerated
      sister. Recombination acts downstream of FANCI-FANCD2, yet RAD51 binds ICL
      stalled replication forks independently of FANCI-FANCD2 and before DSB formation.
      Our results elucidate the functional link between the Fanconi anemia pathway and
      the recombination machinery during ICL repair. In addition, they demonstrate the
      complete repair of a DSB via homologous recombination in vitro.

PMID- 21719679
TI  - A key enzyme in the biogenesis of lysosomes is a protease that regulates
      cholesterol metabolism.
AB  - Mucolipidosis II is a severe lysosomal storage disorder caused by defects in the
      alpha and beta subunits of the hexameric N-acetylglucosamine-1-phosphotransferase
      complex essential for the formation of the mannose 6-phosphate targeting signal
      on lysosomal enzymes. Cleavage of the membrane-bound alpha/beta-subunit precursor
      by an unknown protease is required for catalytic activity. Here we found that the
      alpha/beta-subunit precursor is cleaved by the site-1 protease (S1P) that
      activates sterol regulatory element-binding proteins in response to cholesterol
      deprivation. S1P-deficient cells failed to activate the alpha/beta-subunit
      precursor and exhibited a mucolipidosis II-like phenotype. Thus, S1P functions in
      the biogenesis of lysosomes, and lipid-independent phenotypes of S1P deficiency
      may be caused by lysosomal dysfunction.

PMID- 21719680
TI  - Oxytocin selectively gates fear responses through distinct outputs from the
      central amygdala.
AB  - Central amygdala (CeA) projections to hypothalamic and brain stem nuclei regulate
      the behavioral and physiological expression of fear, but it is unknown whether
      these different aspects of the fear response can be separately regulated by the
      CeA. We combined fluorescent retrograde tracing of CeA projections to nuclei that
      modulate fear-related freezing or cardiovascular responses with in vitro
      electrophysiological recordings and with in vivo monitoring of related behavioral
      and physiological parameters. CeA projections emerged from separate neuronal
      populations with different electrophysiological characteristics and different
      response properties to oxytocin. In vivo, oxytocin decreased freezing responses
      in fear-conditioned rats without affecting the cardiovascular response. Thus,
      neuropeptidergic signaling can modulate the CeA outputs through separate neuronal
      circuits and thereby individually steer the various aspects of the fear response.

PMID- 21719681
TI  - Following the crowd: brain substrates of long-term memory conformity.
AB  - Human memory is strikingly susceptible to social influences, yet we know little
      about the underlying mechanisms. We examined how socially induced memory errors
      are generated in the brain by studying the memory of individuals exposed to
      recollections of others. Participants exhibited a strong tendency to conform to
      erroneous recollections of the group, producing both long-lasting and temporary
      errors, even when their initial memory was strong and accurate. Functional brain
      imaging revealed that social influence modified the neuronal representation of
      memory. Specifically, a particular brain signature of enhanced amygdala activity
      and enhanced amygdala-hippocampus connectivity predicted long-lasting but not
      temporary memory alterations. Our findings reveal how social manipulation can
      alter memory and extend the known functions of the amygdala to encompass socially
      mediated memory distortions.

PMID- 21719682
TI  - Advanced nursing experience is beneficial for lowering the peritonitis rate in
      patients on peritoneal dialysis.
AB  - OBJECTIVES: We explored the relationship between the experience level of nurses
      and the peritonitis risk in peritoneal dialysis (PD) patients. METHODS: Our
      observational cohort study followed 305 incident PD patients until a first
      episode of peritonitis, death, or censoring. Patients were divided into 3 groups
      according to the work experience in general medicine of their nurses-that is,
      least experience (<10 years), moderate experience (10 to <15 years), and advanced
      experience (>= 15 years). Demographic characteristics, baseline biochemistry, and
      residual renal function were also recorded. Multivariate Cox regression was used
      to analyze the association of risks for all-cause and gram-positive peritonitis
      with patient training provided by nurses at different experience levels. RESULTS:
      Of the 305 patients, 91 were trained at the initiation of PD by nurses with
      advanced experience, 100 by nurses with moderate experience, and 114 by nurses
      with the least experience. Demographic and clinical variables did not vary
      significantly between the groups. During 13 582 patient-months of follow-up, 129
      first episodes of peritonitis were observed, with 48 episodes being attributed to
      gram-positive organisms. Kaplan-Meier analysis showed that training by nurses
      with advanced experience predicted the longest period free of first-episode gram
      positive peritonitis. After adjustment for some recognized confounders, the
      advanced experience group was still associated with the lowest risk for first
      episode gram-positive peritonitis. The level of nursing experience was not
      significantly correlated with all-cause peritonitis risk. CONCLUSIONS: The
      experience in general medicine of nurses might help to lower the risk of gram
      positive peritonitis among PD patients. These data are the first to indicate that
      nursing experience in areas other than PD practice can be vital in the training
      of PD patients.

PMID- 21719683
TI  - Activation of p38 mitogen-activated protein kinase promotes peritoneal fibrosis
      by regulating fibrocytes.
AB  - BACKGROUND: Peritoneal fibrosis is a serious complication of long-term peritoneal
      dialysis, and yet the precise pathogenic mechanisms of peritoneal fibrosis remain
      unknown. Fibrocytes participate in tissue fibrosis and express chemokine
      receptors that are necessary for migration. The p38 mitogen-activated protein
      kinase (MAPK) pathway regulates the production of chemokines and has been
      demonstrated to contribute to the pathogenesis of various fibrotic conditions.
      Accordingly, we used an experimental mouse model of peritoneal fibrosis to
      examine the dependency of fibrocytes on p38MAPK signaling. METHODS: Peritoneal
      fibrosis was induced in mice by the injection of 0.1% chlorhexidine gluconate
      (CG) into the abdominal cavity. Mice were treated with FR167653, a specific
      inhibitor of p38MAPK, and immunohistochemical studies were performed to detect
      fibrocytes and cells positive for phosphorylated p38MAPK. The involvement of
      p38MAPK in the activation of fibrocytes also was also investigated in vitro.
      RESULTS: Fibrocytes infiltrated peritoneum in response to CG, and that response
      was accompanied by progressive peritoneal fibrosis. The phosphorylation of
      p38MAPK, as defined by CD45+ spindle-shaped cells, was detected both in
      peritoneal mesothelial cells and in fibrocytes. The level of peritoneal
      expression of CCL2, a chemoattractant for fibrocytes, was upregulated by CG
      injection, and treatment with FR167653 reduced the number of cells positive for
      phosphorylated p38MAPK, the peritoneal expression of CCL2, and the extent of
      peritoneal fibrosis. Pretreatment with FR167653 inhibited the expression of
      procollagen type I alpha1 induced by transforming growth factor-beta1.
      CONCLUSIONS: Our results suggest that p38MAPK signaling contributes to peritoneal
      fibrosis by regulating fibrocyte function.

PMID- 21719684
TI  - Three-dimensional invasion of epithelial-mesenchymal transition-positive human
      peritoneal mesothelial cells into collagen gel is promoted by the concentration
      gradient of fibronectin.
AB  - BACKGROUND: In long-term peritoneal dialysis, myofibroblast-like cells found in
      the interstitium of the peritoneum are assumed to be a transformed type of
      mesothelial cell-epithelial-mesenchymal transition-positive [EMT(+)] human
      peritoneal mesothelial cells (HPMCs)-because they express a mesothelial marker,
      cytokeratin. However, no direct evidence about how these cells are able to invade
      from the mesothelium has yet been obtained. AIM: In this study, we aimed to
      verify whether EMT(+) HPMCs would, in vitro, invade three-dimensionally along
      certain chemotactic factors. METHODS: We used reverse-transcriptase polymerase
      chain reaction to measure expression of Snail, E-cadherin, alpha(5)-integrin, and
      matrix metalloproteinase 2 (MMP2) messenger RNA (mRNA) in HPMCs exposed to 10
      ng/mL transforming growth factor beta1 (TGFbeta1) and how that expression
      corresponds to cell motility, as represented by a video movie. We used the
      Transwell (12 MUm pore diameter: Sigma-Aldrich, Tokyo, Japan) to construct a
      three-dimensional (3D) cell migration chamber. In the lower chamber, a
      concentration gradient of fibronectin (FN) or albumin(Alb) was formed in 0.1%
      type I collagen by diffusion (C(0)=22 nmol/L; concentration gradient:
      C/C(0)=0.7). All cells beneath the membrane were counted 72 hours after 5*10(4)
      EMT(+) HPMCs (HPMCs after a 48-hour exposure to 10 ng/mL TGFbeta1) had been
      spread in the upper chamber. RESULTS: After 72 hours, the increased motility of
      HPMCs resulting from their exposure to 10 ng/mL TGFbeta1 had returned to
      baseline, but they retained an elongated morphology. Expression of Snail and MMP2
      mRNA reached maximum at 24 hours. Expression of E-cadherin declined, and
      expression of alpha(5)-integrin increased continuously. In the 3D invasion study,
      significantly enhanced invasion by EMT(+) but not EMT(-) HPMCs was clearly seen
      in the presence of a FN concentration gradient (p<0.01), although invasion by
      EMT(+) and EMT(-) HPMCs in the absence of a FN concentration gradient was not
      statistically significantly different. Compared with the EMT(+) control (no
      concentration gradient), invasion by EMT(+) HPMCs was 2.1 +/- 0.5 times (p<0.05)
      and 1.4 +/- 0.4 times (p=nonsignificant) higher along the FN and Alb
      concentration gradients respectively. Increased invasion along the FN
      concentration gradient was significantly inhibited (p<0.05) when the HPMCs were
      pre-incubated with 5 MUg/mL RGDS (a blocker for alpha(5)-integrin to FN).
      CONCLUSIONS: We conclude that EMT(+) HPMCs invade collagen gel along the FN
      concentration gradient because of specific binding to RGDS receptors, which bind
      integrins such as alpha(5)-integrin, upregulating invasion-related gene
      expression associated with synthesis of the cytoskeleton protein alpha smooth
      muscle actin.

PMID- 21719685
TI  - Microbiology and outcomes of peritonitis in Australian peritoneal dialysis
      patients.
AB  - We analyzed data from the Australia and New Zealand Dialysis and Transplant
      Registry for 1 October 2003 to 31 December 2008 with the aim of describing the
      nature of peritonitis, therapies, and outcomes in patients on peritoneal dialysis
      (PD) in Australia. At least 1 episode of PD was observed in 6639 patients. The
      overall peritonitis rate was 0.60 episodes per patient-year (95% confidence
      interval: 0.59 to 0.62 episodes), with 6229 peritonitis episodes occurring in
      3136 patients. Of those episodes, 13% were culture-negative, and 11% were
      polymicrobial. Gram-positive organisms were isolated in 53.4% of single-organism
      peritonitis episodes, and gram-negative organisms, in 23.6%. Mycobacterial and
      fungal peritonitis episodes were rare. Initial antibiotic therapy for most
      peritonitis episodes used 2 agents (most commonly vancomycin and an
      aminoglycoside); in 77.2% of episodes, therapy was subsequently changed to a
      single agent. Tenckhoff catheter removal was required in 20.4% of cases at a
      median of 6 days, and catheter removal was more common in fungal, mycobacterial,
      and anaerobic infections, with a median time to removal of 4 - 5 days.
      Peritonitis was the cause of death in 2.6% of patients. Transfer to hemodialysis
      and hospitalization were frequent outcomes of peritonitis. There was no
      relationship between center size and peritonitis rate. The peritonitis rate in
      Australia between 2003 and 2008 was higher than that reported in many other
      countries, with a particularly higher rate of gram-negative peritonitis.

PMID- 21719686
TI  - High rates of mortality and technique failure in peritoneal dialysis patients
      after critical illness.
AB  - INTRODUCTION: Little is known regarding the causes and outcomes of peritoneal
      dialysis (PD) patients admitted to the intensive care unit (ICU). We explored the
      outcomes of technique failure and mortality in a cohort of PD patients admitted
      to the ICU. METHODS: Using a provincial database of 990 incident PD patients
      followed from January 1997 to June 2009, we identified 90 (9%) who were admitted
      to the ICU. Parametric and nonparametric tests were used as appropriate to
      determine differences in baseline characteristics. The Cox proportional hazards
      and competing risk methods were used to investigate associations. RESULTS:
      Compared with other patients, those admitted to the ICU had been on PD longer (p
      < 0.0001) and were more often on continuous ambulatory PD (74.2% vs 25.8%, p =
      0.016). Cardiac problems were the most common admitting diagnosis (50%), followed
      by sepsis (23%), with peritonitis accounting for 69% of the sepsis admissions.
      The 1-year mortality was 53.3%, with 12% alive and converted to hemodialysis, and
      one third remaining alive on PD. In multivariate Cox modeling, age [hazard ratio
      (HR): 1.01; 95% confidence interval (CI): 0.99 to 1.03], white blood cell count
      (HR: 1.02; 95% CI: 1.00 to 1.04), temperature (HR: 0.75; 95% CI: 0.61 to 0.92),
      and peritonitis (1.64; 95% CI: 1.21 to 2.22) at admission to the ICU were
      associated with the composite outcome of technique failure or death. In a
      competing risk analysis, the risk for death was 30%, and for technique failure,
      36% at 1 year. CONCLUSIONS: Patients on PD have high rates of death and technique
      failure after admission to the ICU.

PMID- 21719687
TI  - Using nonfasting lipids--hemodilution or convenience?

PMID- 21719688
TI  - Aspirin in the primary prevention of myocardial infarction.

PMID- 21719689
TI  - D-dimer testing in laboratory practice.
AB  - BACKGROUND: D-dimer is a reliable and sensitive index of fibrin deposition and
      stabilization. As such, its presence in plasma should be indicative of thrombus
      formation. There are many conditions unrelated to thrombosis in which D-dimer
      concentrations are high, however, making its positive predictive value rather
      poor. CONTENT: Notwithstanding these limitations, D-dimer can be regarded as a
      most valuable laboratory tool to diagnose and manage a vast array of thrombosis
      related clinical conditions, including (a) diagnosis of venous thromboembolism
      (VTE), (b) identification of individuals at increased risk of first thrombotic
      event (both arterial and venous), (c) identification of individuals at increased
      risk of recurrent VTE, (d) establishment of the optimal duration of secondary
      prophylaxis after a first episode of VTE, (e) pregnancy monitoring, and (f)
      diagnosis/monitoring of disseminated intravascular coagulation (DIC). This
      article is aimed at reviewing the merits and pitfalls of these applications.
      SUMMARY: From my analysis of the literature, I draw the following conclusions.
      (a) D-dimer, as measured by a sensitive test, can be safely used to exclude VTE
      in symptomatic outpatients, provided that it is used in combination with the
      pretest clinical probability. (b) High concentrations of D-dimer are associated
      with an increased risk of recurrent VTE. (c) Patients who present with D-dimer
      above cutoff after stopping the regular course of oral anticoagulation benefit
      from extended prophylaxis. (d) Finally, D-dimer can be used as a fibrin-related
      degradation marker for the diagnosis/management of patients with DIC.

PMID- 21719690
TI  - AUXIN BINDING PROTEIN1: the outsider.
AB  - AUXIN BINDING PROTEIN1 (ABP1) is one of the first characterized proteins that
      bind auxin and has been implied as a receptor for a number of auxin responses.
      Early studies characterized its auxin binding properties and focused on rapid
      electrophysiological and cell expansion responses, while subsequent work
      indicated a role in cell cycle and cell division control. Very recently, ABP1 has
      been ascribed a role in modulating endocytic events at the plasma membrane and
      RHO OF PLANTS-mediated cytoskeletal rearrangements during asymmetric cell
      expansion. The exact molecular function of ABP1 is still unresolved, but its main
      activity apparently lies in influencing events at the plasma membrane. This
      review aims to connect the novel findings with the more classical literature on
      ABP1 and to point out the many open questions that still separate us from a
      comprehensive model of ABP1 action, almost 40 years after the first reports of
      its existence.

PMID- 21719691
TI  - The plant-specific actin binding protein SCAB1 stabilizes actin filaments and
      regulates stomatal movement in Arabidopsis.
AB  - Microfilament dynamics play a critical role in regulating stomatal movement;
      however, the molecular mechanism underlying this process is not well understood.
      We report here the identification and characterization of STOMATAL CLOSURE
      RELATED ACTIN BINDING PROTEIN1 (SCAB1), an Arabidopsis thaliana actin binding
      protein. Plants lacking SCAB1 were hypersensitive to drought stress and exhibited
      reduced abscisic acid-, H(2)O(2)-, and CaCl(2)-regulated stomatal movement. In
      vitro and in vivo analyses revealed that SCAB1 binds, stabilizes, and bundles
      actin filaments. SCAB1 shares sequence similarity only with plant proteins and
      contains a previously undiscovered actin binding domain. During stomatal closure,
      actin filaments switched from a radial orientation in open stomata to a
      longitudinal orientation in closed stomata. This switch took longer in scab1
      plants than in wild-type plants and was correlated with the delay in stomatal
      closure seen in scab1 mutants in response to drought stress. Our results suggest
      that SCAB1 is required for the precise regulation of actin filament
      reorganization during stomatal closure.

PMID- 21719692
TI  - STENOFOLIA regulates blade outgrowth and leaf vascular patterning in Medicago
      truncatula and Nicotiana sylvestris.
AB  - Dicot leaf primordia initiate at the flanks of the shoot apical meristem and
      extend laterally by cell division and cell expansion to form the flat lamina, but
      the molecular mechanism of lamina outgrowth remains unclear. Here, we report the
      identification of STENOFOLIA (STF), a WUSCHEL-like homeobox transcriptional
      regulator, in Medicago truncatula, which is required for blade outgrowth and leaf
      vascular patterning. STF belongs to the MAEWEST clade and its inactivation by the
      transposable element of Nicotiana tabacum cell type1 (Tnt1) retrotransposon
      insertion leads to abortion of blade expansion in the mediolateral axis and
      disruption of vein patterning. We also show that the classical lam1 mutant of
      Nicotiana sylvestris, which is blocked in lamina formation and stem elongation,
      is caused by deletion of the STF ortholog. STF is expressed at the adaxial
      abaxial boundary layer of leaf primordia and governs organization and outgrowth
      of lamina, conferring morphogenetic competence. STF does not affect formation of
      lateral leaflets but is critical to their ability to generate a leaf blade. Our
      data suggest that STF functions by modulating phytohormone homeostasis and
      crosstalk directly linked to sugar metabolism, highlighting the importance of
      coordinating metabolic and developmental signals for leaf elaboration.

PMID- 21719693
TI  - Analysis of cytokinin mutants and regulation of cytokinin metabolic genes reveals
      important regulatory roles of cytokinins in drought, salt and abscisic acid
      responses, and abscisic acid biosynthesis.
AB  - Cytokinins (CKs) regulate plant growth and development via a complex network of
      CK signaling. Here, we perform functional analyses with CK-deficient plants to
      provide direct evidence that CKs negatively regulate salt and drought stress
      signaling. All CK-deficient plants with reduced levels of various CKs exhibited a
      strong stress-tolerant phenotype that was associated with increased cell membrane
      integrity and abscisic acid (ABA) hypersensitivity rather than stomatal density
      and ABA-mediated stomatal closure. Expression of the Arabidopsis thaliana
      ISOPENTENYL-TRANSFERASE genes involved in the biosynthesis of bioactive CKs and
      the majority of the Arabidopsis CYTOKININ OXIDASES/DEHYDROGENASES genes was
      repressed by stress and ABA treatments, leading to a decrease in biologically
      active CK contents. These results demonstrate a novel mechanism for survival
      under abiotic stress conditions via the homeostatic regulation of steady state CK
      levels. Additionally, under normal conditions, although CK deficiency increased
      the sensitivity of plants to exogenous ABA, it caused a downregulation of key ABA
      biosynthetic genes, leading to a significant reduction in endogenous ABA levels
      in CK-deficient plants relative to the wild type. Taken together, this study
      provides direct evidence that mutual regulation mechanisms exist between the CK
      and ABA metabolism and signals underlying different processes regulating plant
      adaptation to stressors as well as plant growth and development.

PMID- 21719694
TI  - Vitrification of human ICSI/IVF spermatozoa without cryoprotectants: new
      capillary technology.
AB  - The aim of this study was to develop and to test the standardized aseptic 
      technology of permeable cryoprotectant-free vitrification of human spermatozoa 
      in capillaries (for intracytoplasmic sperm injection [ICSI] or in vitro 
      fertilization [IVF]). To test the effect of vitrification on basic sperm 
      parameters, each of 68 swim-up-prepared ejaculates from  oligo-astheno-terato
      zoospermic patients were aliquoted and distributed into 3  groups: 1) nontreated
      control, 2) 10 MUL of spermatozoa cryopreserved by  slow conventional freezing
      with glycerol-contented medium, and 3) 10 MUL of  spermatozoa vitrified in 50-MUL
      plastic capillaries in culture medium with  0.25 M sucrose. Spermatozoa motility
      (1, 24, and 48 hours after warming),  plasma membrane integrity, acrosomal
      integrity, and spontaneous  capacitation-like changes were determined after
      warming. Aseptic  cryoprotectant-free vitrification showed a significantly
      stronger  cryoprotective effect compared with conventional freezing. One hour
      after  warming, motility, plasma membrane integrity, and acrosomal integrity were
      significantly higher than is observed for conventionally frozen spermatozoa 
      (28% vs 18%, 56% vs 22%, and 55% vs 21%, respectively; P < .05),  although lower
      than in fresh spermatozoa (35%, 96%, and 84%, respectively;  P < .05).
      Capacitation-like changes did not differ significantly  between vitrified and
      conventionally frozen samples (8% vs 9%, respectively;  P > .1) (2% in fresh
      spermatozoa). The newly developed technology  of aseptic vitrification of human
      spermatozoa in capillaries can effectively  preserve these cells from cryo
      injures. Spermatozoa, vitrified by this  technology, are free from seminal plasma
      owing to swim-up preceding  vitrification and are free from permeable
      cryoprotectants. They are ready for  further use immediately after warming
      without any additional treatment.  Therefore, the reported technology has a great
      potential for use in  ICSI/IVF.

PMID- 21719695
TI  - Association between Peyronie disease and low serum testosterone levels: detection
      and therapeutic considerations.
AB  - The aim of this paper was to find a link between Peyronie disease (PD) and 
      bioavailable testosterone (bT)/free testosterone (fT) blood levels. Subjects 
      with no erectile dysfunction were prospectively studied with respect to 3 
      parameters: differences in bT/fT between 106 PD patients and 99 healthy 
      controls; differences in plaque area, penile curvature, and pain between 54 PD 
      patients with low bT/fT and 52 PD patients with normal bT/fT; and differences  in
      intraplaque verapamil efficacy between 20 hypogonadal PD patients  supplemented
      with testosterone and 23 hypogonadal PD patients administered a  placebo. Medical
      history, objective examination, and dynamic duplex scanning  of the penis, both
      before and 8 months after the end of the therapy (ie, at  the end of the study
      period), were used to assess PD. Testosterone  supplementation was carried out
      with testosterone buccal adhesive patches 2  * 30 mg/d for the entire study
      period. bT and fT were significantly  lower in PD patients than in control
      patients. The plaque area was  significantly higher in PD patients with low bT/fT
      than in patients with  normal bT/fT. No significant difference emerged when pain
      or penile deformity  were examined. Plaque area and penile curvature improved to
      a greater extent  when intraplaque verapamil injections were associated with
      testosterone  administration than when associated with a placebo. Men with PD had
      lower  bT/fT than healthy controls. In these patients, supplementation with 
      testosterone improved the efficacy of intraplaque verapamil. Plaque area and 
      penile curvature were more severe in hypogonadal PD.

PMID- 21719696
TI  - Preclinical derivation and imaging of autologously transplanted canine induced
      pluripotent stem cells.
AB  - Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new
      avenue for future applications of regenerative medicine. However, before iPSCs
      can be used in a clinical setting, it is critical to validate their in vivo fate
      following autologous transplantation. Thus far, preclinical studies have been
      limited to small animals and have yet to be conducted in large animals that are
      physiologically more similar to humans. In this study, we report the first
      autologous transplantation of iPSCs in a large animal model through the
      generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and
      canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs
      using the following techniques: (i) immunostaining and quantitative PCR for the
      presence of pluripotent and germ layer-specific markers in differentiated ciPSCs;
      (ii) microarray analysis that demonstrates similar gene expression profiles
      between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays;
      and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously
      transplanted to the canine heart was tracked in vivo using clinical positron
      emission tomography, computed tomography, and magnetic resonance imaging. To
      demonstrate clinical potential of ciPSCs to treat models of injury, we generated
      endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient
      murine models of myocardial infarction and hindlimb ischemia.

PMID- 21719697
TI  - Effects of viscogens on RNA transcription inside reovirus particles.
AB  - The dsRNA genome of mammalian reovirus (MRV), like the dsDNA genomes of
      herpesviruses and many bacteriophages, is packed inside its icosahedral capsid in
      liquid-crystalline form, with concentrations near or more than 400 mg/ml.
      Viscosity in such environments must be high, but the relevance of viscosity for
      the macromolecular processes occurring there remains poorly characterized. Here,
      we describe the use of simple viscogens, glycerol and sucrose, to examine their
      effects on RNA transcription inside MRV core particles. Transcription inside MRV
      cores was strongly inhibited by these agents and to a greater extent than either
      predicted by theory or exhibited by a nonencapsidated transcriptase, suggesting
      that RNA transcription inside MRV cores is unusually sensitive to viscogen
      effects. The elongation phase of transcription was found to be a primary target
      of this inhibition. Similar results were obtained with particles of a second
      dsRNA virus, rhesus rotavirus, from a divergent taxonomic subfamily. Polymeric
      viscogens such as polyethylene glycol also inhibited RNA transcription inside MRV
      cores, but in a size-limited manner, suggesting that diffusion through channels
      in the MRV core is required for their activity. Modeling of the data suggested
      that the inherent intracapsid viscosity of both reo- and rotavirus is indeed
      high, two to three times the viscosity of water. The capacity for quantitative
      comparisons of intracapsid viscosity and effects of viscogens on macromolecular
      processes in confined spaces should be similarly informative in other systems.

PMID- 21719698
TI  - Intracellular cannabinoid type 1 (CB1) receptors are activated by anandamide.
AB  - Recent studies have demonstrated that the majority of endogenous cannabinoid type
      1 (CB(1)) receptors do not reach the cell surface but are instead associated with
      endosomal and lysosomal compartments. Using calcium imaging and intracellular
      microinjection in CB(1) receptor-transfected HEK293 cells and NG108-15
      neuroblastoma * glioma cells, we provide evidence that anandamide acting on CB(1)
      receptors increases intracellular calcium concentration when administered
      intracellularly but not extracellularly. The calcium-mobilizing effect of
      intracellular anandamide was dose-dependent and abolished by pretreatment with
      SR141716A, a CB(1) receptor antagonist. The anandamide-induced calcium increase
      was reduced by blocking nicotinic acid-adenine dinucleotide phosphate- or
      inositol 1,4,5-trisphosphate-dependent calcium release and abolished when both
      lysosomal and endoplasmic reticulum calcium release pathways were blocked. Taken
      together, our results indicate that, in CB(1) receptor-transfected HEK293 cells,
      intracellular CB(1) receptors are functional; they are located in acid-filled
      calcium stores (endolysosomes). Activation of intracellular CB(1) receptors
      releases calcium from endoplasmic reticulum and lysosomal calcium stores. In
      addition, our results support a novel role for nicotinic acid-adenine
      dinucleotide phosphate in cannabinoid-induced calcium signaling.

PMID- 21719699
TI  - Kinetic analysis of autotaxin reveals substrate-specific catalytic pathways and a
      mechanism for lysophosphatidic acid distribution.
AB  - Autotaxin (ATX) is a secreted lysophospholipase D that hydrolyzes
      lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), initiating
      signaling cascades leading to cancer metastasis, wound healing, and angiogenesis.
      Knowledge of the pathway and kinetics of LPA synthesis by ATX is critical for
      developing quantitative physiological models of LPA signaling. We measured the
      individual rate constants and pathway of the LPA synthase cycle of ATX using the
      fluorescent lipid substrates FS-3 and 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3
      diazol-4-yl))-LPC. FS-3 binds rapidly (k(1) >=500 MUm(-1) s(-1)) and is
      hydrolyzed slowly (k(2) = 0.024 s(-1)). Release of the first hydrolysis product
      is random and rapid (>=1 s(-1)), whereas release of the second is slow and rate
      limiting (0.005-0.007 s(-1)). Substrate binding and hydrolysis are slow and rate
      limiting with LPC. Product release is sequential with choline preceding LPA. The
      catalytic pathway and kinetics depend strongly on the substrate, suggesting that
      ATX kinetics could vary for the various in vivo substrates. Slow catalysis with
      LPC reveals the potential for LPA signaling to spread to cells distal to the site
      of LPC substrate binding by ATX. An ATX mutant in which catalytic threonine at
      position 210 is replaced with alanine binds substrate weakly, favoring a role for
      Thr-210 in binding as well as catalysis. FTY720P, the bioactive form of a drug
      currently used to treat multiple sclerosis, inhibits ATX in an uncompetitive
      manner and slows the hydrolysis reaction, suggesting that ATX inhibition plays a
      significant role in lymphocyte immobilization in FTY720P-based therapeutics.

PMID- 21719700
TI  - Plant cell nucleolus as a hot spot for iron.
AB  - Many central metabolic processes require iron as a cofactor and take place in
      specific subcellular compartments such as the mitochondrion or the chloroplast.
      Proper iron allocation in the different organelles is thus critical to maintain
      cell function and integrity. To study the dynamics of iron distribution in plant
      cells, we have sought to identify the different intracellular iron pools by
      combining three complementary imaging approaches, histochemistry, micro particle
      induced x-ray emission, and synchrotron radiation micro X-ray fluorescence. Pea
      (Pisum sativum) embryo was used as a model in this study because of its large
      cell size and high iron content. Histochemical staining with ferrocyanide and
      diaminobenzidine (Perls/diaminobenzidine) strongly labeled a unique structure in
      each cell, which co-labeled with the DNA fluorescent stain DAPI, thus
      corresponding to the nucleus. The unexpected presence of iron in the nucleus was
      confirmed by elemental imaging using micro particle-induced x-ray emission. X-ray
      fluorescence on cryo-sectioned embryos further established that, quantitatively,
      the iron concentration found in the nucleus was higher than in the expected iron
      rich organelles such as plastids or vacuoles. Moreover, within the nucleus, iron
      was particularly accumulated in a subcompartment that was identified as the
      nucleolus as it was shown to transiently disassemble during cell division. Taken
      together, our data uncover an as yet unidentified although abundant iron pool in
      the cell, which is located in the nuclei of healthy, actively dividing plant
      tissues. This result paves the way for the discovery of a novel cellular function
      for iron related to nucleus/nucleolus-associated processes.

PMID- 21719701
TI  - Identification of a negative regulatory region for the exchange activity and
      characterization of T332I mutant of Rho guanine nucleotide exchange factor 10
      (ARHGEF10).
AB  - The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was
      previously found in persons with slowed nerve conduction velocities and thin
      myelination of peripheral nerves. However, the molecular and cellular basis of
      the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative
      regulatory region in the N terminus, in which residue 332 is located, and the
      T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant,
      ARHGEF10 DeltaN (lacking amino acids 1-332), induced cell contraction that was
      inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA
      than the wild type. The T332I mutant also showed the phenotype similar to the N
      terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation
      associated phenotype observed in the peripheral nerves is due to activated GEF
      activity of the ARHGEF10 T332I mutant.

PMID- 21719702
TI  - Crystal structure of H2O2-dependent cytochrome P450SPalpha with its bound fatty
      acid substrate: insight into the regioselective hydroxylation of fatty acids at
      the alpha position.
AB  - Cytochrome P450(SPalpha) (CYP152B1) isolated from Sphingomonas paucimobilis is
      the first P450 to be classified as a H(2)O(2)-dependent P450. P450(SPalpha)
      hydroxylates fatty acids with high alpha-regioselectivity. Herein we report the
      crystal structure of P450(SPalpha) with palmitic acid as a substrate at a
      resolution of 1.65 A. The structure revealed that the C(alpha) of the bound
      palmitic acid in one of the alternative conformations is 4.5 A from the heme
      iron. This conformation explains the highly selective alpha-hydroxylation of
      fatty acid observed in P450(SPalpha). Mutations at the active site and the F-G
      loop of P450(SPalpha) did not impair its regioselectivity. The crystal structures
      of mutants (L78F and F288G) revealed that the location of the bound palmitic acid
      was essentially the same as that in the WT, although amino acids at the active
      site were replaced with the corresponding amino acids of cytochrome P450(BSbeta)
      (CYP152A1), which shows beta-regioselectivity. This implies that the high
      regioselectivity of P450(SPalpha) is caused by the orientation of the hydrophobic
      channel, which is more perpendicular to the heme plane than that of P450(BSbeta).

PMID- 21719703
TI  - Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a negative regulator
      of luteinizing/chorionic gonadotropin hormone-induced steroidogenesis in Leydig
      cells: central role of steroidogenic acute regulatory protein (StAR).
AB  - Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a testis-specific
      gonadotropin-regulated RNA helicase that is present in Leydig cells (LCs) and
      germ cells and is essential for spermatid development and completion of
      spermatogenesis. Normal basal levels of testosterone in serum and LCs were
      observed in GRTH null (GRTH(-/-)) mice. However, testosterone production was
      enhanced in LCs of GRTH(-/-) mice compared with WT mice by both in vivo and in
      vitro human chorionic gonadotropin stimulation. LCs of GRTH(-/-) mice had swollen
      mitochondria with a significantly increased cholesterol content in the inner
      mitochondrial membrane. Basal protein levels of SREBP2, HMG-CoA reductase, and
      steroidogenic acute regulatory protein (StAR; a protein that transports
      cholesterol to the inner mitochondrial membrane) were markedly increased in LCs
      of GRTH(-/-) mice compared with WT mice. Gonadotropin stimulation caused an
      increase in StAR mRNA levels and protein expression in GRTH(-/-) mice versus WT
      mice, with no further increase in SREBP2 and down-regulation of HMG-CoA reductase
      protein. The half-life of StAR mRNA was significantly increased in GRTH(-/-)
      mice. Moreover, association of StAR mRNA with GRTH protein was observed in WT
      mice. Human chorionic gonadotropin increased GRTH gene expression and its
      associated StAR protein at cytoplasmic sites. Taken together, these findings
      indicate that, through its negative role in StAR message stability, GRTH
      regulates cholesterol availability at the mitochondrial level. The finding of an
      inhibitory action of GRTH associated with gonadotropin-mediated steroidogenesis
      has provided insights into a novel negative autocrine molecular control mechanism
      of this helicase in the regulation of steroid production in the male.

PMID- 21719704
TI  - Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and
      identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a
      Lyp substrate.
AB  - A missense single-nucleotide polymorphism in the gene encoding the lymphoid
      specific tyrosine phosphatase (Lyp) has been identified as a causal factor in a
      wide spectrum of autoimmune diseases. Interestingly, the autoimmune-predisposing
      variant of Lyp appears to represent a gain-of-function mutation, implicating Lyp
      as an attractive target for the development of effective strategies for the
      treatment of many autoimmune disorders. Unfortunately, the precise biological
      functions of Lyp in signaling cascades and cellular physiology are poorly
      understood. Identification and characterization of Lyp substrates will help
      define the chain of molecular events coupling Lyp dysfunction to diseases. In the
      current study, we identified consensus sequence motifs for Lyp substrate
      recognition using an "inverse alanine scanning" combinatorial library approach.
      The intrinsic sequence specificity data led to the discovery and characterization
      of SKAP-HOM, a cytosolic adaptor protein required for proper activation of the
      immune system, as a bona fide Lyp substrate. To determine the molecular basis for
      Lyp substrate recognition, we solved crystal structures of Lyp in complex with
      the consensus peptide as well as the phosphopeptide derived from SKAP-HOM.
      Together with the biochemical data, the structures define the molecular
      determinants for Lyp substrate specificity and provide a solid foundation upon
      which novel therapeutics targeting Lyp can be developed for multiple autoimmune
      diseases.

PMID- 21719705
TI  - A peroxisome proliferator-activated receptor gamma (PPARgamma)/PPARgamma
      coactivator 1beta autoregulatory loop in adipocyte mitochondrial function.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) activation induces
      adipogenesis and also enhances lipogenesis, mitochondrial activity, and insulin
      sensitivity in adipocytes. Whereas some studies implicate PPARgamma coactivator
      1alpha (PGC-1alpha) in the mitochondrial effect, the mechanisms involved in
      PPARgamma regulation of adipocyte mitochondrial function are not resolved.
      PPARgamma-activating ligands (thiazolidinediones (TZDs)) are important insulin
      sensitizers and were recently shown to indirectly induce PGC-1beta transcription
      in osteoclasts. Here, we asked whether similar effects occur in adipocytes and
      show that TZDs also strongly induce PGC-1beta in cultured 3T3-L1 cells. This
      effect, however, differs from the indirect effect proposed for bone and is rapid
      and direct and involves PPARgamma interactions with an intronic PPARgamma
      response element cluster in the PGC-1beta locus. TZD treatment of cultured
      adipocytes results in up-regulation of mitochondrial marker genes, and increased
      mitochondrial activity and use of short interfering RNA confirms that these
      effects require PGC-1beta. PGC-1beta did not participate in PPARgamma effects on
      adipogenesis or lipogenesis, and PGC-1beta knockdown did not alter insulin
      responsive glucose uptake into 3T3-L1 cells. Similar effects on PGC-1beta and
      mitochondrial gene expression are seen in vivo; fractionation of obese mouse
      adipose tissue reveals that PPARgamma and PGC-1beta, but not PGC-1alpha, are
      coordinately up-regulated in adipocytes relative to preadipocytes and that TZD
      treatment induces PGC-1beta and mitochondrial marker genes in adipose tissue of
      obese mice. We propose that PPARgamma directly induces PGC-1beta expression in
      adipocytes and that this effect regulates adipocyte mitochondrial activity.

PMID- 21719706
TI  - FTY720 (Gilenya) phosphate selectivity of sphingosine 1-phosphate receptor
      subtype 1 (S1P1) G protein-coupled receptor requires motifs in intracellular loop
      1 and transmembrane domain 2.
AB  - FTY720 phosphate (FTY720P) is a high potency agonist for all the endothelial
      differentiation gene family sphingosine 1-phosphate (S1P) receptors except S1P
      receptor subtype 2 (S1P(2)). To map the distinguishing features of S1P(2) ligand
      recognition, we applied a computational modeling-guided mutagenesis strategy that
      was based on the high degree of sequence homology between S1P(1) and S1P(2).
      S1P(2) point mutants of the ligand-binding pocket were characterized. The head
      group-interacting residues Arg3.28, Glu3.29, and Lys7.34 were essential for
      activation. Mutation of residues Ala3.32, Leu3.36, Val5.41, Phe6.44, Trp6.48,
      Ser7.42, and Ser7.46, predicted to interact with the S1P hydrophobic tail,
      impaired activation by S1P. Replacing individual or multiple residues in the
      ligand-binding pocket of S1P(2) with S1P(1) sequence did not impart activation by
      FTY720P. Chimeric S1P(1)/S1P(2) receptors were generated and characterized for
      activation by S1P or FTY720P. The S1P(2) chimera with S1P(1) sequence from the N
      terminus to transmembrane domain 2 (TM2) was activated by FTY720P, and the
      S1P(2)(IC1-TM2)(S1P1) domain insertion chimera showed S1P(1)-like activation.
      Twelve residues in this domain, distributed in four motifs a-d, differ between
      S1P(1) and S1P(2). Insertion of (78)RPMYY in motif b alone or simultaneous
      swapping of five other residues in motifs c and d from S1P(1) into S1P(2)
      introduced FTY720P responsiveness. Molecular dynamics calculations indicate that
      FTY720P binding selectivity is a function of the entropic contribution to the
      binding free energy rather than enthalpic contributions and that preferred
      agonists retain substantial flexibility when bound. After exposure to FTY720P,
      the S1P(2)(IC1-TM2)(S1P1) receptor recycled to the plasma membrane, indicating
      that additional structural elements are required for the selective degradative
      trafficking of S1P(1).

PMID- 21719707
TI  - Substrate specificity of the aspartate:alanine antiporter (AspT) of
      Tetragenococcus halophilus in reconstituted liposomes.
AB  - The aspartate:alanine antiporter (AspT) of the lactic acid bacterium
      Tetragenococcus halophilus is a member of the aspartate:alanine exchanger (AAEx)
      transporter family. T. halophilus AspT catalyzes the electrogenic exchange of L
      aspartate(1-) with L-alanine(0). Although physiological functions of AspT were
      well studied, L-aspartate(1-):L-alanine(0) antiport mechanisms are still
      unsolved. Here we report that the binding sites of L-aspartate and L-alanine are
      independently present in AspT by means of the kinetic studies. We purified His(6)
      tagged T. halophilus AspT and characterized its kinetic properties when
      reconstituted in liposomes (K(m) = 0.35 +/- 0.03 mm for L-aspartate, K(m) = 0.098
      +/- 0 mm for D-aspartate, K(m) = 26 +/- 2 mm for L-alanine, K(m) = 3.3 +/- 0.2 mm
      for D-alanine). Competitive inhibition by various amino acids of L-aspartate or L
      alanine in self-exchange reactions revealed that L-cysteine selectively inhibited
      L-aspartate self-exchange but only weakly inhibited L-alanine self-exchange.
      Additionally, L-serine selectively inhibited L-alanine self-exchange but barely
      inhibited L-aspartate self-exchange. The aspartate analogs L-cysteine sulfinic
      acid, L-cysteic acid, and D-cysteic acid competitively and strongly inhibited L
      aspartate self-exchange compared with L-alanine self-exchange. Taken together,
      these kinetic data suggest that the putative binding sites of L-aspartate and L
      alanine are independently located in the substrate translocation pathway of AspT.

PMID- 21719708
TI  - Understanding the nature of early HCV RNA blips and the use of mathematical
      modeling of viral kinetics during IFN-based therapy.

PMID- 21719709
TI  - Spatial control of cell fate using synthetic surfaces to potentiate TGF-beta
      signaling.
AB  - In organisms, cell-fate decisions result from external cues presented by the
      extracellular microenvironment or the niche. In principle, synthetic niches can
      be engineered to give rise to patterned cell signaling, an advance that would
      transform the fields of tissue engineering and regenerative medicine.
      Biomaterials that display adhesive motifs are critical steps in this direction,
      but promoting localized signaling remains a major obstacle. We sought to exert
      precise spatial control over activation of TGF-beta signaling. TGF-beta
      signaling, which plays fundamental roles in development, tissue homeostasis, and
      cancer, is initiated by receptor oligomerization. We therefore hypothesized that
      preorganizing the transmembrane receptors would potentiate local TGF-beta
      signaling. To generate surfaces that would nucleate the signaling complex, we
      employed defined self-assembled monolayers that present peptide ligands to TGF
      beta receptors. These displays of nondiffusible ligands do not compete with the
      growth factor but rather sensitize bound cells to subpicomolar concentrations of
      endogenous TGF-beta. Cells adhering to the surfaces undergo TGF-beta-mediated
      growth arrest and the epithelial to mesenchymal transition. Gene expression
      profiles reveal that the surfaces selectively regulate TGF-beta responsive genes.
      This strategy provides access to tailored surfaces that can deliver signals with
      spatial control.

PMID- 21719710
TI  - Beta-catenin stimulates pituitary stem cells to form aggressive tumors.

PMID- 21719711
TI  - ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic
      viral infections.
AB  - The effects of the cellular environment on innate immunity remain poorly
      characterized. Here, we show that in Drosophila ATP-sensitive potassium channels
      (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV).
      FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to
      increased viremia and accelerated death. The effect of K(ATP) channels is
      dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an
      activity associated with this potassium channel participates in this antiviral
      pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are
      protected against FHV infection, thus demonstrating the importance of this
      regulation of innate immunity by the cellular environment in the heart. In mice,
      the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant
      animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in
      controls. Together, our data suggest that K(ATP) channel deregulation can have a
      critical impact on innate antiviral immunity in the heart.

PMID- 21719712
TI  - Pharmacists' interventions in the management of patients with chronic kidney
      disease: a systematic review.
AB  - BACKGROUND: Patients with chronic kidney disease have multiple comorbidities and
      require complicated therapeutic regimens. The role of pharmacists caring for
      these patients has been documented, but no review of the impact of these
      interventions has occurred to date. The aim of this work is to assess the impact
      of pharmacists' interventions in patients with chronic kidney disease. METHODS:
      Medline, International Pharmaceutical Abstracts, Pharmacy Abstracts and the
      Cochrane Library were searched for quantitative studies addressing the
      contribution of pharmacists' interventions in patients with chronic kidney
      disease. Quality of controlled studies was assessed using the Downs and Black
      scale. RESULTS: The search identified 37 studies (38 articles), involving 4743
      participants, eligible for inclusion in the review. An uncontrolled design
      corresponded with 80% of the studies. Twenty-one articles (55.3%) reported
      outcome measures and process indicators, 4 (10.5%) reported only outcome measures
      and 13 (34.2%) reported only process indicators. Pharmacists identified 2683 drug
      related problems in 1209 patients. The results from eight controlled studies
      (average quality score 0.57, SD = 0.10) demonstrated that pharmacists'
      interventions reduced all-cause hospitalisations [mean (SD) 1.8 (2.4) versus 3.1
      (3.0), P = 0.02] and cumulative time hospitalised [mean (SD) 9.7 (14.7) versus
      15.5 (16.3) days, P = 0.06], reduced the incidence of end-stage renal disease or
      death in patients with diabetic nephropathy (14.8 versus 28.2 per 100 patient
      years, adjusted relative risk 60%, P < 0.001), improved management of anemia
      (mean 69.8 versus 43.9%, P = 0.0001 and 64.8 versus 40.4%, P = 0.043 patients on
      goal hemoglobin and transferrin saturation, respectively), blood pressure
      [systolic mean (SD) 145.3 (16.8) versus 175.8 (33.9) mmHg, P = 0.029; diastolic
      mean (SD) 77.0 (10.2) versus 91.8 (12.0) mmHg, P = 0.020], calcium and phosphate
      parameters [serum phosphate levels mean (SD) 1.81 (0.54) versus 2.07 (0.25)
      mmol/L, P = 0.03; calcium-phosphate product mean (SD) 4.43 (1.20) versus 4.80
      (0.51) mmol(2)/L(2), P = 0.04] and lipid management [total cholesterol mean (SD)
      4.4 (1.1) versus 5.0 (1.4) mmol/L, P = 0.06; low density lipoprotein cholesterol
      mean (SD) 2.3 (0.9) versus 2.8 (1.0) mmol/L, P = 0.013]. Results from
      uncontrolled studies revealed positive impact of pharmacists' interventions on
      reduced number of transplant rejections [mean (SD) 0.22 (0.42) versus 0.50 (0.51)
      episodes, P = 0.008] and adverse events (49 in 16.0% patients versus 73 in 21.3%
      patients, P < 0.05). CONCLUSIONS: The evidence of pharmacists' interventions in
      patients with chronic kidney disease is sparse, of variable quality and with
      heterogeneous outcomes. On the basis of best available evidence, pharmacists'
      interventions may have a positive impact on outcomes of patients with chronic
      kidney disease.

PMID- 21719713
TI  - Prevalence and predictors of proteinuria in HIV-infected and uninfected pregnant
      women in Cameroon.
AB  - BACKGROUND: Proteinuria during pregnancy has been associated with increased
      pregnancy complications. Furthermore, even low-grade proteinuria has been
      associated with increased mortality in the general population and in non-pregnant
      HIV-infected women. METHODS: Urine dipstick protein was measured prospectively on
      HIV-infected and trace protein or more and quantified by urine protein:creatinine
      measurement (P:C). Logistic regression modeling was used to identify factors
      associated with proteinuria. RESULTS: About 199 human immunodeficiency virus
      (HIV)-infected and 190 HIV-uninfected normotensive pregnant women were evaluated.
      The median age was 27 years in both groups and 37% presented in the third
      trimester. Among HIV-infected women, median CD4 cell count was 417 cells/mm(3);
      27% were on combination antiretroviral therapy (cART). Proteinuria was present in
      39.2% of HIV-infected and 20.9% of uninfected women (P < 0.001). HIV infection
      was independently associated with proteinuria [adjusted odds ratio (OR) = 2.45;
      confidence interval (CI) = 1.56-3.85]. Among HIV-infected pregnant women, cART
      was protective (adjusted OR = 0.39; CI = 0.19-0.82). Results were qualitatively
      similar when urine P:C was evaluated as a continuous outcome variable.
      CONCLUSIONS: The prevalence of low-grade proteinuria in both HIV-infected and 
      uninfected Cameroonian pregnant women is high. HIV-infected pregnant women are at
      increased risk for proteinuria, and cART appears to exert a protective effect.
      Further studies are needed to elucidate the causes of increased proteinuria in
      African pregnant women, both HIV-infected and -uninfected.

PMID- 21719714
TI  - Using microdialysis for early detection of vascular thrombosis after kidney
      transplantation in an experimental porcine model.
AB  - BACKGROUND: In kidney transplantation (KTx), vascular thrombosis has a major
      impact on morbidity and graft survival. The ischaemia, caused by thrombosis, can
      lead to interstitial metabolite changes. The aim of this experimental study was
      to create conditions in which the graft would be prone to vascular thrombosis
      following KTx and then to evaluate the role of microdialysis (MD) for its early
      detection. METHODS: Sixteen randomized pigs in the control group received heparin
      and immunosuppressive drugs, while the case group received none. Based on
      histopathological evidence of vascular thrombosis, the case group was subdivided
      into mildly and severely congested subgroups. Using MD, we evaluated the
      interstitial concentrations of glucose, lactate to pyruvate ratio, glutamate and
      glycerol in the transplanted grafts during different phases of KTx. RESULTS:
      Following reperfusion, we noted considerable changes. The severely congested
      subgroup showed a low and decreasing level of glucose. Only in this group did the
      lactate to pyruvate ratio continue to increase until the end of monitoring. The
      glycerol level increased continuously in the entire case group and this increase
      was most significant in the severely congested subgroup. In all of the study
      groups, glutamate concentration remained in a low steady state until the end of
      monitoring. CONCLUSION: MD can be an appropriate method for early detection of
      vascular complications after KTx. Decreasing glucose levels, increased lactate to
      pyruvate ratio and increased glycerol levels are appropriate indicators for early
      detection of vascular thromboses following KTx. Particularly, the glycerol level
      could predict the necessity and urgency of intervention needed to ultimately save
      the transplanted kidney.

PMID- 21719715
TI  - Towards rational approaches of health care utilization in complex patients: an
      exploratory randomized trial comparing a novel combined clinic to multiple
      specialty clinics in patients with renal disease-cardiovascular disease-diabetes.
AB  - BACKGROUND: Optimal utilization of health care resources for patients with
      chronic conditions is an increasing focus of health care policy researchers and
      clinicians. Kidney disease, diabetes (DM) and cardiovascular disease (CVD) often
      coexist within one individual, but current systems are designed to manage
      individual conditions. We sought to examine if streamlining medical care of
      complex patients (two or more conditions) is associated with similar, worse or
      improved outcomes using a randomized controlled study design. METHODS: Patients
      attending a kidney care clinic (KCC) and at least one other specialty clinic of
      interest (DM, CVD) were randomly assigned to either the 'combined clinic (CC)'
      arm, where resources from all three were integrated into one clinic, or to the
      'standard care' arm with continued attendance at multiple specialty clinics (MC),
      including the KCC. The primary outcome was hospitalization rate and sample size
      was calculated based on non-inferiority. RESULTS: Of 150 subjects enrolled, 11
      subjects exited before study commencement: 139 remained for final analysis. Other
      than older age in the MC group (P = 0.009), the demographics were comparable.
      Hospitalization rates were not different (95% CI for the difference: 0.013-0.207;
      P = 0.03). Similar proportions in each group achieved clinical and laboratory
      targets. Mortality (13%) and dialysis (32%) rates were the same between groups.
      Differences in the cost of clinic visits alone were $86,400 per year in favor of
      the CC. CONCLUSIONS: Medical care of complex patients may be delivered in a
      single combined specialty clinic as compared to multiple disease specific clinics
      without compromising patient care or important health outcomes, with demonstrable
      outpatient costs savings.

PMID- 21719716
TI  - Aristolochic acid nephropathy: variation in presentation and prognosis.
AB  - BACKGROUND: Aristolochic acid nephropathy (AAN) is a worldwide problem and one of
      the common causes of chronic kidney disease (CKD) in China. METHODS: Three
      hundred patients diagnosed as AAN from 1997 to 2006 were enrolled. Medical
      histories of Chinese herb ingestion, clinical-pathological features and risk
      factors for renal failure were recorded. Patients were followed up for 2-156
      months. Factors involved in the prognosis of AAN were investigated. RESULTS: The
      300 patients with AAN manifested three clinical subtypes, including acute kidney
      injury (acute AAN) in 13 patients, abrupt tubular dysfunction with normal serum
      creatinine (Scr) levels in seven cases and chronic tubulointerstitial nephropathy
      with decreased estimated glomerular filtration rate (eGFR) (chronic AAN) in 280
      cases. The acute AAN cases had the highest aristolochic acid (AA)-I intake per
      day and developed progressive kidney failure during 1-7 years follow-up. The
      tubular dysfunction AAN patients had the lowest cumulative AA-I intake and were
      able to keep normal Scr levels during 2-8 years follow-up. The chronic AAN
      patients took the lowest AA-I dose per day but with the longest period and the
      highest cumulative dosage and exhibited a very large range of eGFR changing rate
      (from -21.6 to 5.2, median -3.5 mL/min/year). The cumulative AA-I intake (r =
      0.330, P = 0.045) and the time course from the termination of AA medication to
      the start of follow-up (r = -0.430, P = 0.009) were found to be independent
      factors correlated with the decrease rate of eGFR in the chronic AAN patients. AA
      and the metabolites could be detected in a high frequency in patients who had
      stopped herbal medication for 1 year, which indicates a rather long washout time
      for these chemicals. CONCLUSIONS: AAN has variant phenotypes with distinct
      prognosis, which is determined by the variable AA medications. With better
      understanding of toxic and environmental causes for kidney injury, there would be
      a better chance to uncover the causal factors of cases of 'CKD without known
      causes' which is crucial for improving the disease outcomes.

PMID- 21719717
TI  - Pharmacodynamic effects on biochemical markers of bone turnover and
      pharmacokinetics of the cathepsin K inhibitor, ONO-5334, in an ascending multiple
      dose, phase 1 study.
AB  - Selective inhibitors of cathepsin K, which has a major role in the degradation of
      bone collagen, are potential new treatments for osteoporosis. The
      pharmacokinetics and the pharmacodynamic effects on biochemical markers of bone
      turnover of the new cathepsin K inhibitor, ONO-5334, were investigated in a
      multiple ascending dose, phase 1 study. A total of 120 healthy postmenopausal
      women were enrolled, and doses of 10 to 600 mg once daily and 50 and 300 mg twice
      daily were evaluated in 15- and 28-day multiple-dosing cohorts. Plasma ONO-5334
      concentration reached steady state within 2 days. Twenty-four hours after the
      last dose in the 15-day multiple-dose cohort, 100, 300, and 600 mg once daily
      reduced urinary C-terminal telopeptide of type I collagen by a mean (+/- standard
      deviation) 44.9% +/- 13.6%, 84.5% +/- 4.4%, and 92.5% +/- 1.3%, respectively. The
      28-day cohort showed similar effects. There were far smaller effects on bone
      specific alkaline phosphatase (B-ALP), tartrate-resistant acid phosphatase 5b
      (TRAP5b), or osteocalcin (OC) (measured after 28 days). ONO-5334 was well
      tolerated up to 600 mg/d and for up to 28 days of multiple dosing. Multiple
      dosing with ONO-5334 100 mg resulted in considerable suppression of bone
      resorption markers with no appreciable effects on bone formation markers (B-ALP,
      OC) or osteoclast number (TRAP5b).

PMID- 21719718
TI  - Pharmacokinetics and safety of the lopinavir/ritonavir tablet 500/125 mg twice
      daily coadministered with efavirenz in healthy adult participants.
AB  - A study was conducted in healthy adults (n = 19) to evaluate the pharmacokinetics
      of lopinavir/ritonavir when coadministered with efavirenz. Participants were
      administered lopinavir/ritonavir 400/100 mg alone twice daily (bid) from the
      morning of day 1 through the morning of day 10, and then lopinavir/ritonavir
      500/125 mg bid was coadministered with efavirenz 600 mg every evening (qhs) from
      the evening of day 10 through day 20. Lopinavir and ritonavir exposures when
      administered alone versus with efavirenz were determined on days 10 and 20 and
      compared using point estimates and 90% confidence intervals. The point estimates
      for the ratios of lopinavir maximum observed plasma concentration (C(max)),
      plasma concentration prior to morning dosing (C(trough)), and area under the
      plasma concentration-time curve over a dosing interval (AUC(12)) were 1.121,
      0.954, and 1.060, respectively. The lopinavir/ritonavir dose of 500/125 mg bid
      administered with efavirenz most closely approximates the pharmacokinetic
      exposure of lopinavir/ritonavir 400/100 mg bid administered alone.

PMID- 21719719
TI  - Quality initiatives: measuring and managing the procedural competency of
      radiologists.
AB  - Many regulatory and oversight groups require that the professional performance of
      radiologists be evaluated on an ongoing basis. Although the diagnostic accuracy
      of radiologists is routinely measured at most institutions by means of peer
      review processes, systems for evaluating procedural competency are not widely
      available. Consequently, technical skills are seldom, if ever, evaluated or
      managed. The key elements of a system for evaluating procedural competency
      include the following: (a) clear definition of all elements of a transparent
      evaluation process; (b) definition of standards for training and credentialing
      and options for maintenance of competency certification in interventional
      procedures; (c) collection and analysis of process and outcomes metrics; (d)
      multisource feedback on procedural, patient care, and safety skills; and (e) an
      effective, anonymous process for managing radiologists in whom deficiencies are
      identified. Although no ideal system for evaluating procedural competency
      currently exists, inclusion of these elements goes a long way toward facilitating
      the introduction of a simple process for providing appropriate feedback to
      procedural radiologists, acknowledging excellence, and identifying and managing
      deficiencies if they occur.

PMID- 21719720
TI  - Muscle damage alters the metabolic response to dynamic exercise in humans: a 31P
      MRS study.
AB  - We used 31P-magnetic resonance spectroscopy to test the hypothesis that exercise
      induced muscle damage (EIMD) alters the muscle metabolic response to dynamic
      exercise, and that this contributes to the observed reduction in exercise
      tolerance following EIMD in humans. Ten healthy, physically active men performed
      incremental knee extensor exercise inside the bore of a whole body 1.5-T
      superconducting magnet before (pre) and 48 h after (post) performing 100 squats
      with a load corresponding to 70% of body mass. There were significant changes in
      all markers of muscle damage [perceived muscle soreness, creatine kinase activity
      (434% increase at 24 h), and isokinetic peak torque (16% decrease at 24 h)]
      following eccentric exercise. Muscle phosphocreatine concentration ([PCr]) and pH
      values during incremental exercise were not different pre- and post-EIMD (P >
      0.05). However, resting inorganic phosphate concentration ([P(i)]; pre: 4.7 +/-
      0.8; post: 6.7 +/- 1.7 mM; P < 0.01) and, consequently, [P(i)]/[PCr] values (pre:
      0.12 +/- 0.02; post: 0.18 +/- 0.05; P < 0.01) were significantly elevated
      following EIMD. These mean differences were maintained during incremental
      exercise (P < 0.05). Time to exhaustion was significantly reduced following EIMD
      (519 +/- 56 and 459 +/- 63 s, pre- and post-EIMD, respectively, P < 0.001). End
      exercise pH (pre: 6.75 +/- 0.04; post: 6.83 +/- 0.04; P < 0.05) and [PCr] (pre:
      7.2 +/- 1.7; post: 14.5 +/- 2.1 mM; P < 0.01) were higher, but end-exercise
      [P(i)] was not significantly different (pre: 19.7 +/- 1.9; post: 21.1 +/- 2.6 mM,
      P > 0.05) following EIMD. The results indicate that alterations in phosphate
      metabolism, specifically the elevated [P(i)] at rest and throughout exercise, may
      contribute to the reduced exercise tolerance observed following EIMD.

PMID- 21719721
TI  - Influence of tongue muscle contraction and transmural pressure on nasopharyngeal
      geometry in the rat.
AB  - The mammalian pharynx is a hollow muscular tube that participates in ingestion
      and respiration, and its size, shape, and stiffness can be altered by contraction
      of skeletal muscles that lie inside or outside of its walls. MRI was used to
      determine the interaction between pharyngeal pressure and selective stimulation
      of extrinsic tongue muscles on the shape of the rat nasopharynx. Pressure (-9, 
      6, -3, 3, 6, and 9 cmH2O) was applied randomly to the isolated pharyngeal airway
      of anesthetized rats that were positioned in a 4.7-T MRI scanner. The anterior
      posterior (AP) and lateral diameters of the nasopharynx were measured in eight
      axial slices at each level of pressure, with and without bilateral hypoglossal
      nerve stimulation (0.1-ms pulse, 1/3 maximal force, 80 Hz). The rat nasopharynx
      is nearly circular, and positive pharyngeal pressure caused similar expansion of
      AP and lateral diameters; as a result, airway shape (ratio of lateral to AP
      diameter) remained constant. Negative pressure did not change AP or lateral
      diameter significantly, suggesting that a negative pressure reflex activated the
      tongue or other pharyngeal muscles. Stimulation of tongue protrudor muscles alone
      or coactivation of protrudor and retractor muscles caused greater AP than lateral
      expansion, making the nasopharynx slightly more elliptical, with the long axis in
      the AP direction. These effects tended to be more pronounced at negative
      pharyngeal pressures and greater in the caudal than rostral nasopharynx. These
      data show that stimulation of rodent tongue muscles can adjust pharyngeal shape,
      extending previous work showing that tongue muscle contraction alters pharyngeal
      compliance and volume, and provide physiological insight that can be applied to
      the treatment of obstructive sleep apnea.

PMID- 21719722
TI  - Depressed contractile performance and reduced fatigue resistance in single
      skinned fibers of soleus muscle after long-term disuse in rats.
AB  - Long-term disuse results in atrophy in skeletal muscle, which is characterized by
      reduced functional capability, impaired locomotor condition, and reduced
      resistance to fatigue. Here we show how long-term disuse affects contractility
      and fatigue resistance in single fibers of soleus muscle taken from the hindlimb
      immobilization model of the rat. We found that long-term disuse results in
      depression of caffeine-induced transient contractions in saponin-treated single
      fibers. However, when normalized to maximal Ca(2+)-activated force, the magnitude
      of the transient contractions became similar to that in control fibers. Control
      experiments indicated that the active force depression in disused muscle is not
      coupled with isoform switching of myosin heavy chain or troponin, or with
      disruptions of sarcomere structure or excessive internal sarcomere shortening
      during contraction. In contrast, our electronmicroscopic observation supported
      our earlier observation that interfilament lattice spacing is expanded after
      disuse. Then, to investigate the molecular mechanism of the reduced fatigue
      resistance in disused muscle, we compared the inhibitory effects of inorganic
      phosphate (Pi) on maximal Ca(2+)-activated force in control vs. disused fibers.
      The effect of Pi was more pronounced in disused fibers, and it approached that
      observed in control fibers after osmotic compression. These results suggest that
      contractile depression in disuse results from the lowering of myofibrillar force
      generating capacity, rather than from defective Ca(2+) mobilization, and the
      reduced resistance to fatigue is from an enhanced inhibitory effect of Pi coupled
      with a decrease in the number of attached cross bridges, presumably due to
      lattice spacing expansion.

PMID- 21719723
TI  - The cerebral critical oxygen threshold of ventilated preterm lambs and the
      influence of antenatal inflammation.
AB  - Perinatal inflammation is associated with adverse neurodevelopmental outcomes,
      which may be partly due to changes in the cerebral oxygen delivery/consumption
      relationship. We aimed to determine the critical oxygen delivery threshold of the
      brain of preterm, ventilated lambs and to determine whether the critical
      threshold is affected by exposure to inflammation in utero. Pregnant ewes
      received intra-amniotic injection of lipopolysaccharide or saline at 125 or 127
      days of gestation. Pulmonary and systemic flow probes and catheters were
      surgically positioned in the fetus immediately before delivery at 129 days of
      gestation. After delivery, lambs were ventilated for 90 min using a positive end
      expiratory pressure recruitment strategy. Cardio-respiratory variables and blood
      gases were measured regularly. Systemic and cerebral oxygen delivery, consumption
      (Fick), and extraction were calculated, and the relationship between cerebral
      delivery and consumption analyzed. Linear regression was used to define the
      transition or "critical" oxygen threshold as the point at which the slope of the
      oxygen delivery/consumption curve changed to be > 10 degrees . Four subgroups
      were defined according to the calculated critical threshold. A total of 150
      measurements were recorded in 18 lambs. Fetal cerebral oxygen consumption was
      increased by antenatal lipopolysaccharide (P < 0.05). The postnatal critical
      oxygen threshold was 3.6 ml.kg-1.min-1, corresponding to cerebral oxygen
      consumption of 0.73 ml.kg-1.min-1. High oxygen delivery and consumption were
      associated with increased pulmonary and carotid blood flow and systemic
      extraction compared with low oxygen delivery and consumption. No postnatal effect
      of antenatal inflammation was observed. Inflammation in utero increases fetal,
      but not postnatal, cerebral oxygen consumption. Adverse alterations to pulmonary
      blood flow can result in reduced cerebral blood flow, oxygen delivery, and
      consumption. Regardless of exposure to inflammation, there is a consistent
      postnatal relationship between cerebral oxygen delivery and consumption.

PMID- 21719724
TI  - Variability, measuring the spice of life.

PMID- 21719725
TI  - MicroRNA 132 alters sleep and varies with time in brain.
AB  - MicroRNA (miRNA) levels in brain are altered by sleep deprivation; however, the
      direct effects of any miRNA on sleep have not heretofore been described. We
      report herein that intracerebroventricular application of a miRNA-132 mimetic
      (preMIR-132) decreased duration of non-rapid-eye-movement sleep (NREMS) while
      simultaneously increasing duration of rapid eye movement sleep (REMS) during the
      light phase. Further, preMIR-132 decreased electroencephalographic (EEG) slow
      wave activity (SWA) during NREMS, an index of sleep intensity. In separate
      experiments unilateral supracortical application of preMIR-132 ipsilaterally
      decreased EEG SWA during NREMS but did not alter global sleep duration. In
      addition, after ventricular or supracortical injections of preMIR-132, the
      mimetic-induced effects were state specific, occurring only during NREMS. After
      local supracortical injections of the mimetic, cortical miRNA-132 levels were
      higher at the time sleep-related EEG effects were manifest. We also report that
      spontaneous cortical levels of miRNA-132 were lower at the end of the sleep
      dominant light period compared with at the end of the dark period in rats.
      Results suggest that miRNAs play a regulatory role in sleep and provide a new
      tool for investigating sleep regulation.

PMID- 21719726
TI  - Airway epithelial wounds in rhesus monkey generate ionic currents that guide cell
      migration to promote healing.
AB  - Damage to the respiratory epithelium is one of the most critical steps to many
      life-threatening diseases, such as acute respiratory distress syndrome and
      chronic obstructive pulmonary disease. The mechanisms underlying repair of the
      damaged epithelium have not yet been fully elucidated. Here we provide
      experimental evidence suggesting a novel mechanism for wound repair: endogenous
      electric currents. It is known that the airway epithelium maintains a voltage
      difference referred to as the transepithelial potential. Using a noninvasive
      vibrating probe, we demonstrate that wounds in the epithelium of trachea from
      rhesus monkeys generate significant outward electric currents. A small slit wound
      produced an outward current (1.59 MUA/cm(2)), which could be enhanced (nearly
      doubled) by the ion transport stimulator aminophylline. In addition, inhibiting
      cystic fibrosis transmembrane conductance regulator (CFTR) with CFTR(Inh)-172
      significantly reduced wound currents (0.17 MUA/cm(2)), implicating an important
      role of ion transporters in wound induced electric potentials. Time-lapse video
      microscopy showed that applied electric fields (EFs) induced robust directional
      migration of primary tracheobronchial epithelial cells from rhesus monkeys,
      towards the cathode, with a threshold of <23 mV/mm. Reversal of the field
      polarity induced cell migration towards the new cathode. We further demonstrate
      that application of an EF promoted wound healing in a monolayer wound healing
      assay. Our results suggest that endogenous electric currents at sites of tracheal
      epithelial injury may direct cell migration, which could benefit restitution of
      damaged airway mucosa. Manipulation of ion transport may lead to novel
      therapeutic approaches to repair damaged respiratory epithelium.

PMID- 21719727
TI  - Insignificant response of the fetal placental circulation to arterial hypotension
      in sheep.
AB  - Infusion of the angiotensin-converting enzyme inhibitor enalaprilat into fetal
      sheep caused a profound arterial hypotension within days. Five fetal lambs were
      infused with enalaprilat for 8 days starting at day 128 of gestation. Total
      accumulated dose was 0.30 +/- 0.11 mg/kg. Arterial pressure decreased from 43.6
      to 25.6 mmHg; venous pressure did not change. Biventricular output was not
      statistically significantly changed; placental blood flow decreased almost in
      proportion to the decrease in pressure but the increase in somatic flow was not
      statistically significant. There were no significant changes in pressure 30 min
      after the initial 50-MUg loading dose of enalaprilat. However, the arterial
      pressure responses to test doses of ANG I were largely abolished. After 1 day,
      however, there was a significant decrease in somatic vascular resistance, which
      became stronger with time, but almost no decrease in the placental resistance. We
      conclude that the fetal somatic circulation exhibits a slow but strong decrease
      in resistance but that the response to hypotension is weak or absent in the fetal
      placenta, possibly because it is already fully relaxed.

PMID- 21719728
TI  - Effect of age and weight on upper airway function in a mouse model.
AB  - Defects in pharyngeal mechanical and neuromuscular control are required for the
      development of obstructive sleep apnea. Obesity and age are known sleep apnea
      risk factors, leading us to hypothesize that specific defects in upper airway
      neuromechanical control are associated with weight and age in a mouse model. In
      anesthetized, spontaneously breathing young and old wild-type C57BL/6J mice,
      genioglossus electromyographic activity (EMG(GG)) was monitored and upper airway
      pressure-flow dynamics were characterized during ramp decreases in nasal pressure
      (Pn, cmH2O). Specific body weights were targeted by controlling caloric intake.
      The passive critical pressure (Pcrit) was derived from pressure-flow
      relationships during expiration. The Pn threshold at which inspiratory flow
      limitation (IFL) developed and tonic and phasic EMG(GG) activity during IFL were
      quantified to assess the phasic modulation of pharyngeal patency. The passive
      Pcrit increased progressively with increasing body weight and increased more in
      the old than young mice. Tonic EMG(GG) decreased and phasic EMG(GG) increased
      significantly with obesity. During ramp decreases in Pn, IFL developed at a
      higher (less negative) Pn threshold in the obese than lean mice, although the
      frequency of IFL decreased with age and weight. The findings suggest that weight
      imposes mechanical loads on the upper airway that are greater in the old than
      young mice. The susceptibility to upper airway obstruction increases with age and
      weight as tonic neuromuscular activity falls. IFL can elicit phasic responses in
      normal mice that mitigate or eliminate the obstruction altogether.

PMID- 21719729
TI  - Blood pressure changes alter tracheobronchial cough: computational model of the
      respiratory-cough network and in vivo experiments in anesthetized cats.
AB  - We tested the hypothesis, motivated in part by a coordinated computational cough
      network model, that alterations of mean systemic arterial blood pressure (BP)
      influence the excitability and motor pattern of cough. Model simulations
      predicted suppression of coughing by stimulation of arterial baroreceptors. In
      vivo experiments were conducted on anesthetized spontaneously breathing cats.
      Cough was elicited by mechanical stimulation of the intrathoracic airways.
      Electromyograms (EMG) of inspiratory parasternal, expiratory abdominal, laryngeal
      posterior cricoarytenoid (PCA), and thyroarytenoid muscles along with esophageal
      pressure (EP) and BP were recorded. Transiently elevated BP significantly reduced
      cough number, cough-related inspiratory, and expiratory amplitudes of EP, peak
      parasternal and abdominal EMG, and maximum of PCA EMG during the expulsive phase
      of cough, and prolonged the cough inspiratory and expiratory phases as well as
      cough cycle duration compared with control coughs. Latencies from the beginning
      of stimulation to the onset of cough-related diaphragm and abdominal activities
      were increased. Increases in BP also elicited bradycardia and isocapnic
      bradypnea. Reductions in BP increased cough number; elevated inspiratory EP
      amplitude and parasternal, abdominal, and inspiratory PCA EMG amplitudes;
      decreased total cough cycle duration; shortened the durations of the cough
      expiratory phase and cough-related abdominal discharge; and shortened cough
      latency compared with control coughs. Reduced BP also produced tachycardia,
      tachypnea, and hypocapnic hyperventilation. These effects of BP on coughing
      likely originate from interactions between barosensitive and respiratory
      brainstem neuronal networks, particularly by modulation of respiratory neurons
      within multiple respiration/cough-related brainstem areas by baroreceptor input.

PMID- 21719730
TI  - Cardiovascular changes during underwater static and dynamic breath-hold dives in
      trained divers.
AB  - Limited information exists concerning arterial blood pressure (BP) changes in
      underwater breath-hold diving. Simulated chamber dives to 50 m of freshwater
      (mfw) reported very high levels of invasive BP in two divers during static apnea
      (SA), whereas a recent study using a noninvasive subaquatic sphygmomanometer
      reported unchanged or mildly increased values at 10 m SA dive. In this study we
      investigated underwater BP changes during not only SA but, for the first time,
      dynamic apnea (DA) and shortened (SHT) DA in 16 trained breath-hold divers.
      Measurements included BP (subaquatic sphygmomanometer), ECG, and pulse oxymetry
      (arterial oxygen saturation, SpO2, and heart rate). BP was measured during dry
      conditions, at surface fully immersed (SA), and at 2 mfw (DA and SHT DA), whereas
      ECG and pulse oxymetry were measured continuously. We have found significantly
      higher mean arterial pressure (MAP) values in SA (~40%) vs. SHT DA (~30%).
      Postapneic recovery of BP was slightly slower after SHT DA. Significantly higher
      BP gain (mmHg/duration of apnea in s) was found in SHT DA vs. SA. Furthermore, DA
      attempts resulted in faster desaturation vs. SA. In conclusion, we have found
      moderate increases in BP during SA, DA, and SHT DA. These cardiovascular changes
      during immersed SA and DA are in agreement with those reported for dry SA and DA.

PMID- 21719731
TI  - beta-Adrenergic receptors desensitization is not involved in exercise-induced
      cardiac fatigue: NADPH oxidase-induced oxidative stress as a new trigger.
AB  - Prolonged strenuous exercise (PSE) induces transient left ventricular (LV)
      dysfunction. Previous studies suggest that beta-adrenergic pathway
      desensitization could be involved in this phenomenon, but it remains to be
      confirmed. Moreover, other underlying mechanisms involving oxidative stress have
      been recently proposed. The present study aimed to evaluate the involvement of
      both the beta-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative
      stress in myocardial dysfunction in rats following PSE. Rats were divided into 4
      groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which
      Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO,
      respectively). We evaluated cardiac function in vivo and ex vivo during basal
      conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI)
      release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in
      LV developed pressure, intrinsic myocardial contractility, and relaxation
      associated with an increase in plasma cTnI release. Our in vivo and ex vivo
      results demonstrated no differences in myocardial response to isoproterenol and
      of effective dose 50 between control and PSE rats. Interestingly, the LV
      dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented
      cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units
      (au): 1.98 +/- 0.07 vs. 1.35 +/- 0.10; P < 0.001]. However, no differences in MDA
      were observed between groups. These data suggest that myocardial dysfunction
      observed after PSE was not due to beta-adrenergic receptor desensitization but
      could be due to a signaling oxidative stress from the Nox enzyme.

PMID- 21719732
TI  - A 2-year-old female with Fever and rash.

PMID- 21719733
TI  - Improved detection and quantitation of human BK polyomavirus by PCR assay.

PMID- 21719734
TI  - Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat analysis
      and Beijing/W family of Mycobacterium tuberculosis.

PMID- 21719736
TI  - Acid secretion-associated translocation of KCNJ15 in gastric parietal cells.
AB  - Potassium ions are required for gastric acid secretion. Several potassium
      channels have been implicated in providing K(+) at the apical membrane of
      parietal cells. In examining the mRNA expression levels between gastric mucosa
      and liver tissue, KCNJ15 stood out as the most highly specific K(+) channel in
      the gastric mucosa. Western blot analysis confirmed that KCNJ15 is abundant in
      the stomach. Immunofluorescence staining of isolated gastric glands indicated
      that KCNJ15 was expressed in parietal cells and chief cells, but not in mucous
      neck cells. In resting parietal cells, KCNJ15 was mainly found in puncta
      throughout the cytoplasm but was distinct from H(+)-K(+)-ATPase. Upon
      stimulation, KCNJ15 and H(+)-K(+)-ATPase become colocalized on the apical
      membranes, as suggested by immunofluorescence staining. Western blot analysis of
      the resting and the stimulated membrane fractions confirmed this observation.
      From nonsecreting preparations, KCNJ15-containing vesicles sedimented after a 4-h
      centrifugation at 100,000 g, but not after a 30-min spin, which did sediment most
      of the H(+)-K(+)-ATPase-containing tubulovesicles. Most of the KCNJ15 containing
      small vesicle population was depleted upon stimulation of parietal cells, as
      indicated by the fact that the KCNJ15 signal was shifted to a large membrane
      fraction that sedimented at 4,000 g. Our results demonstrate that, in
      nonsecreting parietal cells, KCNJ15 is stored in vesicles distinct from the H(+)
      K(+)-ATPase-enriched tubulovesicles. Furthermore, upon stimulation, KCNJ15 and
      H(+)-K(+)-ATPase both translocate to the apical membrane for active acid
      secretion. Thus KCNJ15 can be added to the family of apical K(+) channels in
      gastric parietal cells.

PMID- 21719737
TI  - Physiological stress exacerbates murine colitis by enhancing proinflammatory
      cytokine expression that is dependent on IL-18.
AB  - Psychological stress is an environmental factor considered to be a precipitating
      factor of inflammatory bowel disease. Interleukin (IL)-18 plays a role in stress
      induced aggravation in some diseases. The aim of this study was to establish a
      model of murine colitis exacerbated by psychological stress and to clarify the
      role of IL-18 in this model. Male C57Bl/6 mice and IL-18(-/-) mice were used for
      this study. The mice received dextran sulfate sodium (DSS) for induction of
      colitis. Some mice were exposed to psychological stress using a communication
      box. Body weight, colonic length, and histological inflammation were measured for
      assessment of colitis. Tumor necrosis factor (TNF)-alpha and IL-18 expression in
      the colon and IL-18 expression in the adrenal gland were analyzed using real-time
      PCR. The effect of anti-IL-18 antibody was also investigated. Effects of TNF
      alpha and IL-18 on cytokine expressions were studied using the colonic epithelial
      cell line LS174T. Induction of psychological stress in DSS-treated wild-type mice
      significantly exacerbated colitis with enhanced expression of proinflammatory
      cytokines and IL-18. However, induction of psychological stress in DSS-treated IL
      18(-/-) mice did not aggravate colitis compared with that in the IL-18(-/-) group
      given only DSS treatment. Stress-induced aggravation of colitis was ameliorated
      significantly by anti-IL-18 antibody treatment. IL-18 did not enhance TNF-alpha
      induced expression of intercellular adhesion molecule-1 or IL-8 in LS174T. We
      established a model of colitis exacerbated by psychological stress. Psychological
      stress enhanced IL-18 expression and plays a proinflammatory role in stress
      induced aggravation of colitis.

PMID- 21719738
TI  - Ostalpha depletion protects liver from oral bile acid load.
AB  - Bile acid homeostasis is tightly maintained through interactions between the
      liver, intestine, and kidney. During cholestasis, the liver is incapable of
      properly clearing bile acids from the circulation, and alternative excretory
      pathways are utilized. In obstructive cholestasis, urinary elimination is often
      increased, and this pathway is further enhanced after bile duct ligation in mice
      that are genetically deficient in the heteromeric, basolateral organic solute
      transporter alpha-beta (Ostalpha-Ostbeta). In this study, we examined renal and
      intestinal function in Ostalpha-deficient and wild-type mice in a model of bile
      acid overload. After 1% cholic acid feeding, Ostalpha-deficient mice had
      significantly lower serum ALT levels compared with wild-type controls, indicating
      partial protection from liver injury. Urinary clearance of bile acids, but not
      clearance of [(3)H]inulin, was significantly higher in cholic acid-fed Ostalpha
      deficient mice compared with wild-type mice but was not sufficient to account for
      the protection. Fecal excretion of bile acids over the 5 days of cholic acid
      feeding was responsible for almost all of the bile acid loss in Ostalpha
      deficient mice, suggesting that intestinal losses of bile acids accounted for the
      protection from liver injury. Thus fecal loss of bile acids after bile acid
      overload reduced the need for the kidney to filter and excrete the excess bile
      acids. In conclusion, Ostalpha-deficient mice efficiently eliminate excess bile
      acids via the feces. Inhibition of intestinal bile acid absorption might be an
      effective therapeutic target in early stages of cholestasis when bile acids are
      still excreted into bile.

PMID- 21719739
TI  - Role of astrocytes and altered regulation of spinal glutamatergic
      neurotransmission in stress-induced visceral hyperalgesia in rats.
AB  - Glutamate (Glu) is the primary excitatory neurotransmitter in the central nervous
      system and plays a critical role in the neuroplasticity of nociceptive networks.
      We aimed to examine the role of spinal astroglia in the modulation of
      glutamatergic neurotransmission in a model of chronic psychological stress
      induced visceral hyperalgesia in male Wistar rats. We assessed the effect of
      chronic stress on different glial Glu control mechanisms in the spinal cord
      including N-methyl-d-aspartate receptors (NMDARs), glial Glu transporters (GLT1
      and GLAST), the Glu conversion enzyme glutamine synthetase (GS), and glial
      fibrillary acidic protein (GFAP). We also tested the effect of pharmacological
      inhibition of NMDAR activation, of extracellular Glu reuptake, and of astrocyte
      function on visceral nociceptive response in naive and stressed rats. We observed
      stress-induced decreased expression of spinal GLT1, GFAP, and GS, whereas GLAST
      expression was upregulated. Although visceral hyperalgesia was blocked by
      pharmacological inhibition of spinal NMDARs, we observed no stress effects on
      NMDAR subunit expression or phosphorylation. The glial modulating agent
      propentofylline blocked stress-induced visceral hyperalgesia, and blockade of
      GLT1 function in control rats resulted in enhanced visceral nociceptive response.
      These findings provide evidence for stress-induced modulation of glia-controlled
      spinal Glu-ergic neurotransmission and its involvement in chronic stress-induced
      visceral hyperalgesia. The findings reported in this study demonstrate a unique
      pattern of stress-induced changes in spinal Glu signaling and metabolism
      associated with enhanced responses to visceral distension.

PMID- 21719740
TI  - Dual effects of interleukin-18: inhibiting hepatitis B virus replication in
      HepG2.2.15 cells and promoting hepatoma cells metastasis.
AB  - Interleukin-18 (IL-18) has been reported to inhibit hepatitis B virus (HBV)
      replication in the liver of HBV transgenic mice; however, the molecular mechanism
      of its antiviral effect has not been fully understood. In the present study, it
      was shown that IL-18 and its receptors (IL-18R) were constitutively expressed in
      hepatoma cell lines HepG2 and HepG2.2.15 as well as normal liver cell line HL
      7702. We demonstrated that IL-18 directly inhibited HBV replication in HepG2.2.15
      cells via downregulating the activities of HBV core and X gene promoters. The
      suppressed HBV replication by IL-18 could be rescued by the administration of
      BAY11-7082, an inhibitor of transcription factor NF-kappaB. On the other hand, it
      was of interest that IL-18 promoted HepG2 cell metastasis and migration dose
      dependently in both wound-healing assays and Transwell assays. The underlying
      mechanism could be partially attributable to the increased activities of
      extracellular matrix metalloproteinase (MMP)-9, MMP-3, and MMP-2 by IL-18, which
      upregulated the mRNA levels of MMP-3 and MMP-9 in a NF-kappaB-dependent manner.
      Furthermore, it was confirmed that expression of IL-18/IL-18R and most MMPs were
      remarkably upregulated in hepatocellular carcinoma (HCC) liver cancer tissue
      specimens, suggesting that IL-18/IL-18R-triggered signaling pathway was closely
      related to HCC metastasis in vivo. Therefore, we revealed the dual effects of IL
      18 in human hepatocytes: it not only inhibited HBV replication but also promoted
      hepatoma cells metastasis and migration. NF-kappaB played a critical role in both
      effects. Our work contributed to a deeper understanding of the biological
      function of IL-18 in human hepatocytes.

PMID- 21719741
TI  - Loss of parietal cell superoxide dismutase leads to gastric oxidative stress and
      increased injury susceptibility in mice.
AB  - Mitochondrial superoxide dismutase (SOD2) prevents accumulation of the superoxide
      that arises as a consequence of oxidative phosphorylation. However, SOD2 is a
      target of oxidative/nitrosative inactivation, and reduced SOD2 activity has been
      demonstrated to contribute to portal hypertensive gastropathy. We investigated
      the consequences of gastric parietal cell-specific SOD2 deficiency on
      mitochondrial function and gastric injury susceptibility. Mice expressing Cre
      recombinase under control of the parietal cell Atpase4b gene promoter were
      crossed with mice harboring loxP sequences flanking the sod2 gene (SOD2 floxed
      mice). Cre-positive mice and Cre-negative littermates (controls) were used in
      studies of SOD2 expression, parietal cell function (ATP synthesis, acid
      secretion, and mitochondrial enzymatic activity), increased oxidative/nitrosative
      stress, and gastric susceptibility to acute injury. Parietal cell SOD2 deficiency
      was accompanied by a 20% (P < 0.05) reduction in total gastric SOD activity and a
      93% (P < 0.001) reduction in gastric SOD2 activity. In SOD2-deficient mice,
      mitochondrial aconitase and ATP synthase activities were impaired by 36% (P <
      0.0001) and 44% (P < 0.005), respectively. Gastric tissue ATP content was reduced
      by 34% (P < 0.002). Basal acid secretion and peak secretagogue (histamine)
      induced acid secretion were reduced by 43% (P < 0.0001) and 40% (P < 0.0005),
      respectively. There was a fourfold (P < 0.02) increase in gastric mucosal
      apoptosis and 41% (P < 0.001) greater alcohol-induced gastric damage in the
      parietal cell SOD2-deficient mice. Our findings indicate that loss of parietal
      cell SOD2 leads to mitochondrial dysfunction, resulting in perturbed energy
      metabolism, impaired parietal cell function, and increased gastric mucosal
      oxidative stress. These alterations render the gastric mucosa significantly more
      susceptible to acute injury.

PMID- 21719742
TI  - A prospective cohort study of menstrual characteristics and time to pregnancy.
AB  - The authors examined the association between menstrual characteristics and time
      to pregnancy among 2,653 Danish women enrolled in a prospective cohort study
      (2007-2009). Menstrual characteristics were reported at baseline. Outcome data
      were updated bimonthly until pregnancy, fertility treatment, loss to follow-up,
      or end of observation (12 cycles). Adjusted fecundability ratios and 95%
      confidence intervals were estimated by using discrete-time Cox regression models.
      Relative to average cycle lengths (27-29 days), fecundability ratios for cycle
      lengths <25, 25-26, 30-31, 32-33, and >=34 days were 0.64 (95% confidence
      interval (CI): 0.49, 0.84), 0.94 (95% CI: 0.77, 1.13), 1.10 (95% CI: 0.97, 1.25),
      1.35 (95% CI: 1.06, 1.73), and 1.17 (95% CI: 0.91, 1.49), respectively. Compared
      with cycles that regularized within 2 years after menarche, fecundability ratios
      for cycles that regularized 2-3 and >=4 years after menarche were 0.90 (95% CI:
      0.80, 1.02) and 0.89 (95% CI: 0.77, 1.03), respectively. Fecundability ratios
      were 0.87 (95% CI: 0.72, 1.05) comparing <3 with 3-4 days of menstrual bleeding
      and 0.70 (95% CI: 0.43, 1.13) comparing very heavy with moderate flow. In the
      present study, shorter cycle length was associated with delayed time to
      pregnancy. Age at menarche, time to menstrual regularization, and duration or
      intensity of menstrual flow were not appreciably associated with fecundability.

PMID- 21719743
TI  - Comparability of different methods for estimating influenza infection rates over
      a single epidemic wave.
AB  - Estimation of influenza infection rates is important for determination of the
      extent of epidemic spread and for calculation of severity indicators. The authors
      compared estimated infection rates from paired and cross-sectional serologic
      surveys, rates of influenza like illness (ILI) obtained from sentinel general
      practitioners (GPs), and ILI samples that tested positive for influenza using
      data from similar periods collected during the 2009 H1N1 epidemic in Singapore.
      The authors performed sensitivity analyses to assess the robustness of estimates
      to input parameter uncertainties, and they determined sample sizes required for
      differing levels of precision. Estimates from paired seroconversion were 17% (95%
      Bayesian credible interval (BCI): 14, 20), higher than those from cross-sectional
      serology (12%, 95% BCI: 9, 17). Adjusted ILI estimates were 15% (95% BCI: 10,
      25), and estimates computed from ILI and laboratory data were 12% (95% BCI: 8,
      18). Serologic estimates were least sensitive to the risk of input parameter
      misspecification. ILI-based estimates were more sensitive to parameter
      misspecification, though this was lessened by incorporation of laboratory data.
      Obtaining a 5-percentage-point spread for the 95% confidence interval in
      infection rates would require more than 1,000 participants per serologic study, a
      sentinel network of 90 GPs, or 50 GPs when combined with laboratory samples. The
      various types of estimates will provide comparable findings if accurate input
      parameters can be obtained.

PMID- 21719744
TI  - A prospective study of bowel movement frequency and risk of Parkinson's disease.
AB  - The authors prospectively examined bowel movement frequency at baseline in
      relation to future Parkinson's disease risk in the Health Professionals Follow-up
      Study (HPFS) during 2000-2006 (33,901 men) and the Nurses' Health Study (NHS)
      during 1982-2006 (93,767 women). During the follow-up (6 years for the HPFS and
      24 years for the NHS), the authors identified 156 incident male Parkinson's
      disease cases (HPFS) and 402 female cases (NHS). In the HPFS, compared with men
      with daily bowel movements, men with a bowel movement every 3 days or less had a
      multivariate-adjusted relative risk of 4.98 (95% confidence interval (CI): 2.59,
      9.57) for developing Parkinson's disease in the next 6 years. In the NHS, the
      corresponding relative risk was 2.15 (95% CI: 0.76, 6.10), and the risk of
      Parkinson's disease was not elevated beyond 6 years of follow-up (relative risks
      = 1.25 for years 7-12, 0.54 for years 13-18, and 0.88 for years 19-24). When
      these 2 cohorts were combined, the pooled relative risks for Parkinson's disease
      in the next 6 years were 0.75, 1 (referent), 2.62, and 3.93 (95% CI: 2.26, 6.84)
      (P(trend) < 0.0001) across 4 bowel movement categories. In conclusion, infrequent
      bowel movements may antedate the onset of cardinal motor symptoms of Parkinson's
      disease and may contribute to the identification of populations with higher than
      average Parkinson's disease risk.

PMID- 21719745
TI  - Smoking before the first pregnancy and the risk of breast cancer: a meta
      analysis.
AB  - The authors conducted a meta-analysis of the association between smoking before a
      first pregnancy, when undifferentiated breast tissue may be vulnerable to tobacco
      carcinogens, and the risk of breast cancer. A search of the published literature
      through August 2010 identified 23 papers reporting on associations between
      smoking before a first pregnancy and breast cancer. Odds ratios or hazard ratios
      and 95% confidence intervals, adjusted for known or suspected breast cancer risk
      factors, were abstracted from each study. Data were pooled using both fixed- and
      random-effects models. The fixed-effect summary risk ratio for breast cancer
      among the women who smoked before their first pregnancy versus women who had
      never smoked was 1.10 (95% confidence interval: 1.07, 1.14); the random-effects
      estimate was similar. The separate fixed-effect risk ratios for smoking only
      before the first pregnancy (5 studies) or only after the first pregnancy (16
      studies) were both 1.07, providing no evidence that breast tissue is more
      susceptible to malignant transformation from smoking before the first pregnancy.
      While these small summary risk ratios may represent causal effects, residual
      confounding could readily produce estimates of this size in the absence of any
      causal effect.

PMID- 21719746
TI  - Population attributable fractions of adenocarcinoma of the esophagus and
      gastroesophageal junction.
AB  - Obesity, gastroesophageal reflux, and smoking have repeatedly been shown to be
      important and independent risk factors for adenocarcinoma of the esophagus (EAC)
      and of the gastroesophageal junction (GEJAC). There have been few attempts,
      however, to quantify the proportion of disease associated with these potentially
      modifiable factors. The authors have estimated the population attributable
      fraction of EAC and GEJAC attributable to obesity, symptoms of gastroesophageal
      reflux, and smoking using data from a population-based case-control study
      conducted in Australia between 2002 and 2005. Cases were patients with EAC (n =
      364) or GEJAC (n = 425). Controls (n = 1,580) were randomly sampled from a
      population register. Combinations of smoking, body mass index (weight in
      kilograms divided by height in meters squared), and gastroesophageal reflux
      together accounted for 76% (95% confidence interval: 66, 84) of EAC cases and 69%
      (95% confidence interval: 58, 78) of GEJAC cases. Individually, high body mass
      index (>=30) and frequent acid reflux (>=1 time/week) accounted for the greatest
      proportions of EAC (23% and 36%, respectively), and smoking and frequent symptoms
      of acid reflux accounted for the greatest proportions of GEJAC (43% and 28%,
      respectively). The present study suggests that these cancers may be largely
      prevented by maintaining healthy body mass index, avoiding smoking, and
      controlling symptomatic gastroesophageal reflux.

PMID- 21719748
TI  - EBM-based Clinical Guidelines for Pancreatic Cancer 2009 from the Japan Pancreas
      Society: a synopsis.

PMID- 21719749
TI  - Clinical implication of p53 overexpression in breast cancer patients younger than
      50 years with a triple-negative subtype who undergo a modified radical
      mastectomy.
AB  - OBJECTIVE: The purpose of this study was to identify the clinicopathological
      characteristics and prognostic value of p53 overexpression in breast cancer
      patients treated with a modified radical mastectomy. METHODS: The medical records
      of 197 patients who had undergone modified radical mastectomy between January
      1991 and December 2008 were reviewed retrospectively. Breast cancer subtype and
      p53 overexpression were investigated using immunohistochemistry and/or
      fluorescent in situ hybridization analysis of surgical specimens. RESULTS: The
      median follow-up after the modified radical mastectomy was 56.1 months (range,
      14.7-232.7). The median age was 47 years (range, 31-72). p53 overexpression was
      noted in 73 patients (37.1%). Breast cancer-specific death rate (P = 0.011),
      cancer progression (P = 0.024), distant metastasis (P = 0.015), hormone receptor
      negativity (P < 0.001) and human epidermal growth factor receptor 2 positivity (P
      = 0.017) were detected more frequently in patients with p53 overexpression. The
      overall survival rates were significantly lower in the p53-overexpression group
      than in the non-p53-overexpression group (P = 0.021, log-rank test). In the
      multivariate analysis, p53 overexpression showed the strongest prognostic
      significance in patients aged <50 years (P = 0.039) and with the triple-negative
      subtype (P = 0.023). CONCLUSIONS: p53 overexpression correlated with breast
      cancer-specific death rates and adverse prognostic factors in patients treated
      with modified radical mastectomy. p53 overexpression might be a more reliable
      prognosticator in patients aged <50 years and with the triple-negative subtype.
      More effective systemic treatments might be warranted for these patients
      exhibiting p53 overexpression. Further validation is required to make more
      definite conclusions.

PMID- 21719750
TI  - Docetaxel followed by fluorouracil/epirubicin/cyclophosphamide as neoadjuvant
      chemotherapy for patients with primary breast cancer.
AB  - OBJECTIVE: This multicenter, open-label, single-arm, Phase II study assessed the
      efficacy of a neoadjuvant chemotherapy with docetaxel (75 mg/m(2) q3w) followed
      by 5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500
      mg/m(2) q3w in patients with early-stage breast cancer. METHODS: Women with
      resectable breast cancer (T1c-3 N0 M0 or T1-3 N1 M0) were enrolled. Before
      surgery, patients received four cycles of docetaxel followed by four cycles of 5
      fluorouracil, epirubicin, and cyclophosphamide. The primary endpoint was the
      pathological complete response (pCR) rate defined for the breast alone, assessed
      by a central review committee. Secondary endpoints included clinical response and
      safety. RESULTS: One hundred and thirty-seven patients were enrolled. Of the 132
      patients assessable for pathologic response, 23% (95% confidence interval, 16
      31%) experienced a pathological complete response and 6% (95% confidence
      interval, 3-12%) had a near pathological complete response (few remaining cancer
      cells), resulting in a quasi-pathological complete response of 29% (95%
      confidence interval, 21-37%). Clinical response rate following the initial
      docetaxel regimen was 64%. The overall clinical response rate after completion of
      5-fluorouracil, epirubicin, and cyclophosphamide was 79%; breast-conserving
      surgery was performed in 79% of patients. More patients with triple-negative
      disease (estrogen/progesterone receptors negative; human epidermal growth factor
      2 negative) experienced a pathological complete response [14/29, (48%); 95%
      confidence interval, 29-68%] versus those with other molecular subtypes. The
      safety profile was acceptable. CONCLUSIONS: Eight cycles of neoadjuvant
      chemotherapy-docetaxel followed by 5-fluorouracil, epirubicin, and
      cyclophosphamide-are tolerable and conferred high rates of pathological complete
      response and breast-conserving surgery. Patients with triple-negative disease
      were more likely to achieve pathological complete response versus other subtypes,
      suggesting that selecting appropriate neoadjuvant chemotherapy based on molecular
      subtype could be possible.

PMID- 21719751
TI  - A case of gastric cancer accompanied with massive splenic invasion by metastatic
      lymph nodes.

PMID- 21719752
TI  - Time trends in stomach cancer mortality (1950-2008) in Japan, the USA and Europe
      based on the WHO mortality database.

PMID- 21719753
TI  - Lung homing of endothelial progenitor cells in humans with asthma after allergen
      challenge.
AB  - RATIONALE: Increased bronchial vascularity is a feature of asthma that can
      contribute to airflow obstruction and progressive decline in lung function.
      Angiogenesis is associated with the lung homing and in situ differentiation of
      endothelial progenitor cells (EPC) in mouse models of asthma. We have previously
      shown that inhibiting allergen (Ag)-induced recruitment of EPC in sensitized mice
      attenuated increased bronchial vascularity and development of airway
      hyperresponsiveness. OBJECTIVES: We investigated the accumulation of EPC and
      formation of new blood vessels in the lungs of human subjects with asthma after
      Ag inhalation challenge. METHODS: Consenting patients with mild atopic asthma (n
      = 13) with FEV1 >= 70%, methacholine PC20 <= 16 mg/ml, and a dual response to Ag
      were recruited. Sputum levels of EPC were determined by multigating flow
      cytometry, and lung vascularity was enumerated by immunostaining with von
      Willebrand factor. MEASUREMENTS AND MAIN RESULTS: Sputum levels of EPC were
      determined by multigating flow cytometry and lung vascularity was enumerated by
      immunostaining with von Willebrand factor. There was a significant increase in
      sputum EPC levels 24 hours post Ag but not diluent challenge. Similarly, a
      significant increase in the number and diameter of blood vessels in lung biopsy
      tissue 24 hours post Ag was observed. In vitro culture of EPC demonstrated the
      capacity of these cells to differentiate into mature endothelial cells and form
      tubelike vessel structures. In sputum supernatants, there was a significant
      increase in CXCR2 agonists, IL-8, and Gro-alpha 24 hours post Ag. Only Gro-alpha
      stimulated a significant EPC migrational response in vitro. CONCLUSIONS: Our data
      suggest that increased lung homing of EPC may promote bronchial vascularity in
      allergic asthmatic responses and that the recruitment of these progenitors maybe
      orchestrated by CXCR2 chemokines.

PMID- 21719754
TI  - Health effects of oil spills: lessons from the Prestige.

PMID- 21719755
TI  - Delayed access and survival in idiopathic pulmonary fibrosis: a cohort study.
AB  - RATIONALE: Idiopathic pulmonary fibrosis is often initially misdiagnosed. Delays
      in accessing subspecialty care could lead to worse outcomes among those with
      idiopathic pulmonary fibrosis. OBJECTIVES: To examine the association between
      delayed access to subspecialty care and survival time in idiopathic pulmonary
      fibrosis. METHODS: We performed a prospective cohort study of 129 adults who met
      American Thoracic Society criteria for idiopathic pulmonary fibrosis evaluated at
      a tertiary care center. Delay was defined as the time from the onset of dyspnea
      to the date of initial evaluation at a tertiary care center. We used competing
      risk survival methods to examine survival time and time to transplantation.
      MEASUREMENTS AND MAIN RESULTS: The mean age was 63 years and 76% were men. The
      median delay was 2.2 years (interquartile range 1.0-3.8 yr), and the median
      follow-up time was 1.1 years. Age and lung function at the time of evaluation did
      not vary by delay. A longer delay was associated with an increased risk of death
      independent of age, sex, forced vital capacity, third-party payer, and
      educational attainment (adjusted hazard ratio per doubling of delay was 1.3, 95%
      confidence interval 1.03 to 1.6). Longer delay was not associated with a lower
      likelihood of undergoing lung transplantation. CONCLUSIONS: Delayed access to a
      tertiary care center is associated with a higher mortality rate in idiopathic
      pulmonary fibrosis independent of disease severity. Early referral to a specialty
      center should be considered for those with known or suspected interstitial lung
      disease.

PMID- 21719756
TI  - Continuity of care in intensive care units: a cluster-randomized trial of
      intensivist staffing.
AB  - RATIONALE: Little is known about the consequences of intensivists' work
      schedules, or intensivist continuity of care. OBJECTIVES: To assess the impact of
      weekend respite for intensivists, with consequent reduction in continuity of
      care, on them and their patients. METHODS: In five medical intensive care units
      (ICUs) in four academic hospitals we performed a prospective, cluster-randomized,
      alternating trial of two intensivist staffing schedules. Daily coverage by a
      single intensivist in half-month rotations (continuous schedule) was compared
      with weekday coverage by a single intensivist, with weekend cross-coverage by
      colleagues (interrupted schedule). We studied consecutive patients admitted to
      study units, and the intensivists working in four of the participating units.
      MEASUREMENTS AND MAIN RESULTS: The primary patient outcome was ICU length of stay
      (LOS);we also assessed hospital LOS and mortality rates. The primary intensivist
      outcome was physician burnout. Analysis was by multivariable regression. A total
      of 45 intensivists and 1,900 patients participated in the study. Continuity of
      care differed between schedules (patients with multiple intensivists = 28% under
      continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and
      mortality were nonsignificantly higher under continuous scheduling (DeltaICU LOS
      0.36 d, P = 0.20; Deltahospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio =
      1.43, P = 0.12; hospital mortality, odds ratio = 1.17,P = 0.41). Intensivists
      experienced significantly higher burnout, work-home life imbalance, and job
      distress working under the continuous schedule. CONCLUSIONS: Work schedules where
      intensivists received weekend breaks were better for the physicians and, despite
      lower continuity of intensivist care, did not worsen outcomes for medical ICU
      patients.

PMID- 21719757
TI  - The National Emphysema Treatment Trial (NETT) Part II: Lessons learned about lung
      volume reduction surgery.
AB  - Substantial information regarding the role of lung volume reduction surgery
      (LVRS) in severe emphysema emanates from the National Emphysema Treatment Trial
      (NETT). The NETT was not a crossover trial and therefore was able to examine the
      effects of optimal medical management and LVRS on short- and long-term
      survival,as well as lung function, exercise performance, and quality of life.The
      NETT generated multiple insights into the preoperative, perioperative,and
      postoperative management of patients undergoing thoracotomy; described pain
      control techniques that were safe and effective; and emphasized the need to
      address nonpulmonary issues to optimize surgical outcomes. After the NETT, newer
      investigation has focused on bronchoscopic endobronchial interventions and other
      techniques less invasive than LVRS to achieve lung reduction.In this review, we
      summarize what we currently know about the role of LVRS in the treatment of
      severe emphysema as a result of insights gained from the NETT and provide a brief
      review of the newer techniques of lung volume reduction.

PMID- 21719758
TI  - Asymmetric dimethylarginine is increased in asthma.
AB  - RATIONALE: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide
      synthase (NOS) inhibitor that competes with L-arginine for binding to NOS. It has
      been suggested that ADMA contributes to inflammation, collagen deposition,
      nitrosative stress, and lung function in murine models. OBJECTIVES: To test the
      hypothesis that ADMA is increased in asthma and that NOS inhibition by ADMA
      contributes to airways obstruction. METHODS: We assessed alterations of L
      arginine, ADMA, and symmetric dimethylarginine (SDMA) levels in a murine model of
      allergic airways inflammation using LC-tandem mass spectrometry. Based on the
      levels of ADMA observed in the murine model, we further tested the direct effects
      of nebulized inhaled ADMA on airways responsiveness in naive control mice. We
      also assessed alterations of L-arginine, ADMA, and SDMA in humans in adult lung
      specimens and sputum samples from pediatric patients with asthma. MEASUREMENTS
      AND MAIN RESULTS: ADMA was increased in lungs from the murine model of allergic
      airways inflammation. Exogenous administration of ADMA to naive mice, at doses
      consistent with the levels observed in the allergically inflamed lungs, resulted
      in augmentation of the airways responsiveness to methacholine. ADMA levels were
      also increased in human asthma lungs and sputum samples. CONCLUSIONS: ADMA levels
      are increased in asthma and contribute to NOS-related pathophysiology.

PMID- 21719759
TI  - Arteriogenesis is modulated by bradykinin receptor signaling.
AB  - RATIONALE: Positive outward remodeling of pre-existing collateral arteries into
      functional conductance arteries, arteriogenesis, is a major endogenous rescue
      mechanism to prevent cardiovascular ischemia. Collateral arterial growth is
      accompanied by expression of kinin precursor. However, the role of kinin
      signaling via the kinin receptors (B1R and B2R) in arteriogenesis is unclear.
      OBJECTIVE: The purpose of this study was to elucidate the functional role and
      mechanism of bradykinin receptor signaling in arteriogenesis. METHODS AND
      RESULTS: Bradykinin receptors positively affected arteriogenesis, with the
      contribution of B1R being more pronounced than B2R. In mice, arteriogenesis upon
      femoral artery occlusion was significantly reduced in B1R mutant mice as
      evidenced by reduced microspheres and laser Doppler flow perfusion measurements.
      Transplantation of wild-type bone marrow cells into irradiated B1R mutant mice
      restored arteriogenesis, whereas bone marrow chimeric mice generated by
      reconstituting wild-type mice with B1R mutant bone marrow showed reduced
      arteriogenesis after femoral artery occlusion. In the rat brain 3-vessel
      occlusion arteriogenesis model, pharmacological blockade of B1R inhibited
      arteriogenesis and stimulation of B1R enhanced arteriogenesis. In the rat,
      femoral artery ligation combined with arterial venous shunt model resulted in
      flow-driven arteriogenesis, and treatment with B1R antagonist R715 decreased
      vascular remodeling and leukocyte invasion (monocytes) into the perivascular
      tissue. In monocyte migration assays, in vitro B1R agonists enhanced migration of
      monocytes. CONCLUSIONS: Kinin receptors act as positive modulators of
      arteriogenesis in mice and rats. B1R can be blocked or therapeutically stimulated
      by B1R antagonists or agonists, respectively, involving a contribution of
      peripheral immune cells (monocytes) linking hemodynamic conditions with
      inflammatory pathways.

PMID- 21719760
TI  - Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for
      pulmonary hypertension in chronic lung disease.
AB  - RATIONALE: Senescence of pulmonary artery smooth muscle cells (PA-SMCs) caused by
      telomere shortening or oxidative stress may contribute to pulmonary hypertension
      associated with chronic lung diseases. OBJECTIVE: To investigate whether cell
      senescence contributes to pulmonary vessel remodeling and pulmonary hypertension
      in chronic obstructive pulmonary disease (COPD). METHODS AND RESULTS: In 124
      patients with COPD investigated by right heart catheterization, we found a
      negative correlation between leukocyte telomere length and pulmonary hypertension
      severity. In-depth investigations of lung vessels and derived cultured PA-SMCs
      showed greater severity of remodeling and increases in senescent p16-positive and
      p21-positive PA-SMCs and proliferating Ki67-stained cells in 14 patients with
      COPD compared to 13 age-matched and sex-matched control subjects who smoke.
      Cultured PA-SMCs from COPD patients displayed accelerated senescence, with fewer
      cell population doublings, an increased percentage of beta-galactosidase-positive
      cells, shorter telomeres, and higher p16 protein levels at an early cell passage
      compared to PA-SMCs from controls. Both in situ and in vitro PA-SMC senescence
      criteria correlated closely with the degree of pulmonary vessel wall hypertrophy.
      Because senescent PA-SMCs stained for p16 and p21 were virtually confined to the
      media near the Ki67-positive cells, which predominated in the neointima and
      hypertrophied media, we evaluated whether senescent cells affected normal PA-SMC
      functions. We found that senescent PA-SMCs stimulated the growth and migration of
      normal target PA-SMCs through the production and release of paracrine soluble and
      insoluble factors. CONCLUSION: PA-SMC senescence is an important contributor to
      the process of pulmonary vascular remodeling that underlies pulmonary
      hypertension in chronic lung disease.

PMID- 21719761
TI  - Plasminogen regulates stromal cell-derived factor-1/CXCR4-mediated hematopoietic
      stem cell mobilization by activation of matrix metalloproteinase-9.
AB  - OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) is a widespread
      therapeutic agent for stimulation of hematopoietic progenitor and stem cell
      (HPSC) mobilization from bone marrow (BM). Plasminogen (Plg) has been shown to be
      critical for HPSC mobilization. Here, we investigated the role of Plg in G-CSF
      induced HPSC mobilization and the underlying mechanism. METHODS AND RESULTS: By
      using gene-targeted mice, our data show that Plg is required for G-CSF-induced
      HPSC egress to sinusoidal capillaries in BM and subsequent mobilization to
      peripheral circulation. G-CSF induced Plg-dependent activation of matrix
      metalloproteinase-9 (MMP-9) in BM, and MMP-9 neutralization or deficiency
      suppressed HPSC migration and mobilization. Reconstitution of MMP-9 activity by
      BM transplantation after lentiviral overexpression rescued HPSC mobilization in
      Plg-deficient mice, indicating that MMP-9 activation is required for Plg-mediated
      HPSC mobilization. Interestingly, after G-CSF simulation, Plg downregulated
      stromal cell-derived factor-1 in BM and spatiotemporally regulated the expression
      of C-X-C chemokine receptor type 4 (CXCR4) on mobilized HPSCs, and reconstitution
      of MMP-9 activity in Plg-deficient mice reversed CXCR4 expression on HPSCs in
      plasma and BM, suggesting that CXCR4 serves as a new downstream signal of Plg/MMP
      9 in HPSC mobilization. CONCLUSIONS: Our data elucidated a novel mechanism that
      Plg regulates MMP-9-dependent CXCR4 expression to facilitate HPSC mobilization in
      response to G-CSF.

PMID- 21719762
TI  - Matrix metalloproteinase (MMP)-3 activates MMP-9 mediated vascular smooth muscle
      cell migration and neointima formation in mice.
AB  - OBJECTIVE: Several matrix metalloproteinases (MMPs) have been implicated in
      extracellular matrix destruction and other actions that lead to plaque rupture
      and myocardial infarction. Conversely, other MMPs have been shown to promote
      vascular smooth muscle cell (VSMC)-driven neointima formation, which contributes
      to restenosis, fibrous cap formation, and plaque stability. MMP-3 knockout
      reduced VSMC accumulation in mouse atherosclerotic plaques, implicating MMP-3 in
      neointima formation. We therefore investigated the effect of MMP-3 knockout on
      neointima formation after carotid ligation in vivo and VSMC migration in vitro.
      METHODS AND RESULTS: Twenty-eight days after left carotid ligation, MMP-3
      knockout significantly reduced neointima formation (75%, P<0.01) compared with
      wild-type (WT) littermates, and also reduced remodeling of ligated and
      contralateral carotid arteries. Gelatin zymography illustrated that MMP-3
      knockout abolished MMP-9 activation in ligated carotids and scratch-wounded VSMC
      cultures. MMP-3 knockout also attenuated VSMC migration into a scratch wound by
      59% compared with WT cells. Addition of exogenous MMP-3 or activated MMP-9
      restored migration of MMP-3 knockouts to that of WT VSMCs, but exogenous MMP-3
      had no effect on migration in MMP-9 knockout VSMCs. MMP-9 knockout or knockdown
      with small interfering RNA significantly retarded VSMC migration to the same
      extent as MMP-3 knockout. CONCLUSIONS: These results indicate for the first time
      that MMP-3 mediated activation of MMP-9 is required for efficient neointima
      formation after carotid ligation in vivo and for VSMC migration in vitro, whereas
      MMP-12 plays a redundant role. These findings add to the understanding of MMP
      action in plaque stability and restenosis.

PMID- 21719763
TI  - Sirtuin 1 retards hyperphosphatemia-induced calcification of vascular smooth
      muscle cells.
AB  - OBJECTIVE: Arterial calcification is associated with cardiovascular disease as a
      complication of advanced atherosclerosis. Aged vascular cells manifest some
      morphological features of a senescent phenotype. Recent studies have demonstrated
      that mammalian sirtuin 1 (SIRT1), a histone deacetylase, is an exciting target
      for cardiovascular disease management. Here, we investigated the role of SIRT1 in
      a calcification model of vascular smooth muscle cells (SMCs). METHODS AND
      RESULTS: In adenine-induced renal failure rats with hyperphosphatemia, massive
      calcification was induced in the aortic media. Senescence-associated beta
      galactosidase (SAbeta-gal) activity, a marker of cellular senescence, in medial
      SMCs was significantly increased, and its induction was positively associated
      with the degree of calcification. In cultured SMCs, inorganic phosphate (Pi)
      stimulation dose-dependently increased SAbeta-gal-positive cells, and Pi-induced
      senescence was associated with downregulation of SIRT1 expression, leading to p21
      activation. The activation via SIRT1 downregulation was blunted by inhibition of
      Pi cotransporter. Activation of SIRT1 by resveratrol significantly reduced the
      senescence-associated calcification. Conversely, SIRT1 knockdown by small
      interfering RNA accelerated the Pi-induced SMC senescence and subsequent
      calcification. In addition, SIRT1 knockdown induced phenotypic change from a
      differentiated state to osteoblast-like cells. The senescence-related SMC
      calcification was completely prevented by p21 knockdown. In addition to Pi
      induced premature senescence, SMCs with replicative senescence were also more
      sensitive to Pi-induced calcification compared with young SMCs, and this finding
      was attributable to augmented p21 expression. CONCLUSIONS: SIRT1 plays an
      essential role in preventing hyperphosphatemia-induced arterial calcification via
      inhibition of osteoblastic transdifferentiation. In addition, Pi-induced SMC
      calcification may be associated with both premature and replicative cellular
      senescence.

PMID- 21719764
TI  - Early ischemic change on CT versus diffusion-weighted imaging for patients with
      stroke receiving intravenous recombinant tissue-type plasminogen activator
      therapy: stroke acute management with urgent risk-factor assessment and
      improvement (SAMURAI) rt-PA registry.
AB  - BACKGROUND AND PURPOSE: Alberta Stroke Programme Early CT Score (ASPECTS) is a
      quantitative topographical score to evaluate early ischemic change in the middle
      cerebral arterial territory on CT as well as on diffusion-weighted imaging (DWI).
      The aim of the present study was to elucidate the relationship between CT-ASPECTS
      and DWI-ASPECTS for patients with hyperacute stroke and their associations with
      outcomes after recombinant tissue-type plasminogen activator therapy based on a
      multicenter registry. METHODS: ASPECTS was assessed on both CT and DWI before
      intravenous 0.6 mg/kg alteplase in 360 patients with stroke (119 women, 71 +/- 11
      years old). The outcomes were symptomatic intracerebral hemorrhage within 36
      hours and independence at 3 months defined by a modified Rankin Scale score of 0
      to 2. RESULTS: DWI-ASPECTS was positively correlated with CT-ASPECTS (rho=0.511,
      P<0.001) and was lower than CT-ASPECTS (median 8 [interquartile range, 6 to 9]
      versus 9 [8 to 10], P<0.001). Higher baseline National Institutes of Health
      Stroke Scale score (standardized partial regression coefficient [beta] 0.061,
      P<0.001) and cardioembolic stroke (beta 0.35, P<0.001) were related to this
      discrepancy. The area under the receiver operating characteristic curve for
      predicting sICH (12 patients) using ASPECTS was 0.673 (95% CI, 0.503 to 0.807) by
      CT and 0.764 (95% CI, 0.635 to 0.858) by DWI (P=0.275). The area for predicting
      independence at 3 months (192 patients) was 0.621 (0.564 to 0.674) by CT and
      0.639 (0.580 to 0.694) by DWI (P=0.535). CONCLUSIONS: For patients with
      hyperacute stroke, DWI-ASPECTS scored approximately 1 point lower than CT
      ASPECTS. Both CT-ASPECTS and DWI-ASPECTS were useful predictors of symptomatic
      intracerebral hemorrhage and independence at 3 months after recombinant tissue
      type plasminogen activator.

PMID- 21719765
TI  - Racial disparities in tissue plasminogen activator treatment rate for stroke: a
      population-based study.
AB  - BACKGROUND AND PURPOSE: Some prior studies have shown that racial disparities
      exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic
      stroke. We sought to determine whether race was associated with tPA treatment for
      stroke in a predominantly black urban population. METHODS: Systematic chart
      abstraction was performed on consecutive hospitalized patients with ischemic
      stroke from all 7 acute care hospitals in the District of Columbia from February
      1, 2008, to January 31, 2009. RESULTS: Of 1044 patients with ischemic stroke, 74%
      were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were
      one third less likely than whites to receive intravenous tPA (3% versus 10%,
      P<0.001). However, blacks were also less likely than whites to present within 3
      hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA
      eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks
      were almost half as likely to be treated with intravenous tPA than whites (27%
      versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar
      for blacks and whites (70% versus 76%, P=0.62). CONCLUSIONS: In this
      predominantly black urban population hospitalized for acute ischemic stroke,
      blacks were significantly less likely to be treated with intravenous tPA due to
      contraindications to treatment, delayed presentation, and stroke severity.
      Effective interventions designed to increase treatment in this population need to
      focus on culturally relevant education programs designed to address barriers
      specific to this population.

PMID- 21719766
TI  - Letter by Romanens regarding article, "carotid plaque area and intima-media
      thickness in prediction of first-ever ischemic stroke: a 10-year follow-up of
      6584 men and women: the tromso study".

PMID- 21719767
TI  - Cost-effectiveness of tissue-type plasminogen activator in the 3- to 4.5-hour
      time window for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine the cost
      effectiveness of tissue-type plasminogen activator (tPA) treatment in the 3- to
      4.5-hour time window after ischemic stroke. METHODS: Decision-analytic and Markov
      state-transition models were created to determine the cost-effectiveness of
      treatment of ischemic stroke patients with intravenous tPA administered in the 3-
      to 4.5-hour time window compared with medical therapy without tPA. Health
      benefits were measured in quality-adjusted life-years (QALYs). The economic
      outcome measure of the model was the difference in estimated healthcare costs
      between the 2 treatment alternatives. The incremental cost-effectiveness ratio
      was calculated by dividing the cost difference by the difference in QALYs. One
      way sensitivity and probabilistic analyses were performed to test the robustness
      of the model. RESULTS: The administration of tPA compared with standard medical
      therapy resulted in a lifetime gain of 0.28 QALYs for an additional cost of
      $6050, yielding an incremental cost-effectiveness ratio of $21 978 per QALY. One
      way sensitivity analyses demonstrated that the incremental cost-effectiveness
      ratio was most sensitive to the cost of hospitalization for patients who received
      tPA. Based on probabilistic analysis, there is an 88% probability that tPA is the
      preferred treatment at a willingness-to-pay threshold of $50 000 per QALY.
      CONCLUSIONS: The balance of costs and benefits favors treatment with intravenous
      tPA in the 3- to 4.5-hour time window. This supports, from a societal
      perspective, the use of tPA therapy in this treatment time window for acute
      ischemic stroke.

PMID- 21719768
TI  - Blood-brain barrier permeability abnormalities in vascular cognitive impairment.
AB  - BACKGROUND AND PURPOSE: Disruption of the blood-brain barrier has been proposed
      to be important in vascular cognitive impairment. Increased cerebrospinal fluid
      albumin and contrast-enhanced MRI provide supporting evidence, but quantification
      of the blood-brain barrier permeability in patients with vascular cognitive
      impairment is lacking. Therefore, we acquired dynamic contrast-enhanced MRI to
      quantify blood-brain barrier permeability in vascular cognitive impairment.
      Method- We studied 60 patients with suspected vascular cognitive impairment. They
      had neurological and neuropsychological testing, permeability measurements with
      dynamic contrast-enhanced MRI, and lumbar puncture to measure albumin index.
      Patients were separated clinically into subcortical ischemic vascular disease
      (SIVD), multiple and lacunar infarcts, and leukoaraiosis. Twenty volunteers were
      controls for the dynamic contrast-enhanced MRI studies, and control cerebrospinal
      fluid was obtained from 20 individuals undergoing spinal anesthesia for
      nonneurological problems. RESULTS: Thirty-six patients were classified as SIVD, 8
      as multiple and lacunar infarcts, and 9 as leukoaraiosis. The albumin index was
      significantly increased in the SIVD group compared with 20 control subjects.
      Permeabilities for the patients with vascular cognitive impairment measured by
      dynamic contrast-enhanced MRI were significantly increased over control subjects
      (P<0.05). Patient age did not correlate with either the blood-brain barrier
      permeability or albumin index. Highest albumin index values were seen in the SIVD
      group (P<0.05) and were significantly increased over multiple and lacunar
      infarcts. K(i) values were elevated over control subjects in SIVD but were
      similar to multiple and lacunar infarcts. CONCLUSIONS: There was abnormal
      permeability in white matter in patients with SIVD as shown by dynamic contrast
      enhanced MRI and albumin index. Future studies will be needed to determine the
      relationship of blood-brain barrier damage and development of white matter
      hyperintensities.

PMID- 21719769
TI  - Withdrawal of antithrombotic agents and its impact on ischemic stroke occurrence.
AB  - BACKGROUND AND PURPOSE: Antithrombotic medications (anticoagulants and
      antiplatelets) are often withheld in the periprocedural period and after bleeding
      complications to limit the risk of new or recurrent bleeding. These medications
      are also stopped by patients for various reasons such as cost, side effects, or
      unwillingness to take medication. METHODS: Patient records from the population
      based Greater Cincinnati/Northern Kentucky Stroke Study were reviewed to identify
      cases of ischemic stroke in 2005 and determine the temporal association of
      strokes with withdrawal of antithrombotic medication. Ischemic strokes and
      reasons for medication withdrawal were identified by study nurses for subsequent
      physician review. RESULTS: In 2005, 2197 cases of ischemic stroke among residents
      of the region were identified through hospital discharge records. Of the 2197
      ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic
      medication withdrawal, 61 (53.5%) of these after stoppage of warfarin and the
      remainder after stoppage of an antiplatelet medication. Of the strokes after
      withdrawal, 71 (62.3%) were first-ever and 43 (37.7%) were recurrent; 54 (47.4%)
      occurred after withdrawal of medication by a physician in the periprocedural
      period. CONCLUSIONS: The withdrawal of antiplatelet and antithrombotic
      medications in the 60 days preceding an acute ischemic stroke was associated with
      5.2% of ischemic strokes in our study population. This finding emphasizes the
      need for thoughtful decision-making concerning antithrombotic medication use in
      the periprocedural period and efforts to improve patient compliance.

PMID- 21719770
TI  - Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the
      Northern Manhattan study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the association
      of vitamin D deficiency and indices of mineral metabolism with subclinical
      carotid markers that predict cardiovascular events. METHODS: Two hundred three
      community-dwelling adults (Northern Manhattan Study; age, 68 +/- 11; age range,
      50 to 93 years) had serum measurements (calcium, phosphorus, 25-hydroxyvitamin D,
      1,25-dihydroxyvitamin D, parathyroid hormone) and carotid ultrasound (plaque
      presence, number, maximal carotid plaque thickness, intima-media thickness).
      RESULTS: Adjusting for cardiovascular risk factors, plaque number was associated
      with phosphorus levels (beta=0.39 per 1-mg/dL increase; P=0.02) and calcium
      phosphorus product (beta=0.36 per 10-U increase; P=0.03). In those with plaque
      (N=116 [57%]), the association of plaque number with phosphorus and calcium
      phosphorus product persisted. In addition, 25-hydroxyvitamin D was inversely
      associated with both intima-media thickness (beta=-0.01 per 10-ng/mL increase;
      P=0.05) and maximal carotid plaque thickness (beta=-0.10 per 10-ng/mL increase;
      P=0.03). In a model containing traditional cardiac risk factors and indices of
      mineral metabolism, 25-hydroxyvitamin D accounted for 13% of the variance in both
      intima-media thickness and maximal carotid plaque thickness. Calcium, parathyroid
      hormone, and 1,25-dihydroxyvitamin D levels were not associated with carotid
      measures. CONCLUSIONS: After adjusting for cardiovascular risk factors and renal
      function, serum phosphorus and calcium-phosphorus product were associated with a
      greater burden of subclinical carotid atherosclerosis. Low 25-hydroxyvitamin D
      levels were associated with increased intima-media thickness and maximal carotid
      plaque thickness in those with plaque, and 25-hydroxyvitamin D contributed in a
      robust manner to the variance in both. These results confirm and extend data on
      the association of low vitamin D levels with subclinical carotid atherosclerosis.
      The precise nature of this association and the optimum levels of vitamin D for
      vascular health remain to be elucidated.

PMID- 21719771
TI  - Correlation of inpatient and outpatient measures of stroke care quality within
      veterans health administration hospitals.
AB  - BACKGROUND AND PURPOSE: Quality of care delivered in the inpatient and ambulatory
      settings may be correlated within an integrated health system such as the
      Veterans Health Administration. We examined the correlation between stroke care
      quality at hospital discharge and within 6 months postdischarge. METHODS: We
      conducted a cross-sectional hospital-level correlation analyses of chart
      abstracted data for 3467 veterans discharged alive after an acute ischemic stroke
      from 108 Veterans Health Administration medical centers and 2380 veterans with
      postdischarge follow-up within 6 months in fiscal year 2007. Four risk
      standardized processes of care represented discharge care quality: prescription
      of antithrombotic and antilipidmic therapy, anticoagulation for atrial
      fibrillation, and tobacco cessation counseling along with a composite measure of
      defect-free care. Five risk-standardized intermediate outcomes represented
      postdischarge care quality: achievement of blood pressure, low-density
      lipoprotein, international normalized ratio, and glycosylated hemoglobin target
      levels, and delivery of appropriate treatment for poststroke depression along
      with a composite measure of achieved outcomes. RESULTS: Median risk-standardized
      composite rate of defect-free care at discharge was 79%. Median risk-standardized
      postdischarge rates of achieving goal were 56% for blood pressure, 36% for low
      density lipoprotein, 41% for international normalized ratio, 40% for glycosylated
      hemoglobin, and 39% for depression management and the median risk-standardized
      composite 6-month outcome rate was 44%. The hospital composite rate of defect
      free care at discharge was correlated with meeting the low-density lipoprotein
      goal (r=0.31; P=0.007) and depression management (r=0.27; P=0.03) goal but was
      not correlated with blood pressure, international normalized ratio, glycosylated
      hemoglobin goals, nor with the composite measure of achieved postdischarge
      outcomes (probability values >0.13). CONCLUSIONS: Hospital discharge care quality
      was not consistently correlated with ambulatory care quality.

PMID- 21719772
TI  - Optimal end points for acute stroke therapy trials: best ways to measure
      treatment effects of drugs and devices.
AB  - BACKGROUND AND PURPOSE: Over the past decade, analysis of completed actual
      trials, model population studies, and theoretical work have improved approaches
      to selecting and analyzing end points in acute stroke treatment trials. METHODS:
      Narrative review. RESULTS: Because stroke affects persons in their biological,
      functional, social, and experiential dimensions, measures of impairment,
      disability, handicap, and quality of life are all desirable in pivotal trials,
      with disability being most important. Scales that are valid, reliable,
      responsive, and easy to administer are preferred; consequently, the modified
      Rankin Scale has become the most widely used single clinical efficacy measure.
      Because stroke cripples and kills, most outcome scales array patient outcome in
      ordered ranks, spread over the entire range from normal to disabled to dead.
      Generally, shift analysis, analyzing all health state transitions concurrently,
      is the most efficient analytic technique to detect treatment effects, with
      sliding dichotomy less efficient and fixed dichotomy least efficient, unless
      treatment effects strongly cluster at 1 or a few health state transitions that
      can be prespecified. Test statistics must also take into account
      interpretability, ie, how well they can be converted into metrics capturing all
      outcomes the intervention might alter in proportion to the degree they are valued
      by the patient; full ordinal analysis is most informative, sliding dichotomy is
      intermediately informative, and fixed dichotomy is least informative regarding
      this global outcome. CONCLUSIONS: Stroke trial power and interpretation can be
      substantially enhanced by adherence to the principles delineated in this review.
      Full ordinal and sliding dichotomy analysis will most often be advantageous
      compared with fixed dichotomous approaches.

PMID- 21719773
TI  - Impairment of speech production predicted by lesion load of the left arcuate
      fasciculus.
AB  - BACKGROUND AND PURPOSE: Previous studies have suggested that patients' potential
      for poststroke language recovery is related to lesion size; however, lesion
      location may also be of importance, particularly when fiber tracts that are
      critical to the sensorimotor mapping of sounds for articulation (eg, the arcuate
      fasciculus) have been damaged. In this study, we tested the hypothesis that
      lesion loads of the arcuate fasciculus (ie, volume of arcuate fasciculus that is
      affected by a patient's lesion) and of 2 other tracts involved in language
      processing (the extreme capsule and the uncinate fasciculus) are inversely
      related to the severity of speech production impairments in patients with stroke
      with aphasia. METHODS: Thirty patients with chronic stroke with residual
      impairments in speech production underwent high-resolution anatomic MRI and a
      battery of cognitive and language tests. Impairment was assessed using 3
      functional measures of spontaneous speech (eg, rate, informativeness, and overall
      efficiency) as well as naming ability. To quantitatively analyze the relationship
      between impairment scores and lesion load along the 3 fiber tracts, we calculated
      tract-lesion overlap volumes for each patient using probabilistic maps of the
      tracts derived from diffusion tensor images of 10 age-matched healthy subjects.
      RESULTS: Regression analyses showed that arcuate fasciculus lesion load, but not
      extreme capsule or uncinate fasciculus lesion load or overall lesion size,
      significantly predicted rate, informativeness, and overall efficiency of speech
      as well as naming ability. CONCLUSIONS: A new variable, arcuate fasciculus lesion
      load, complements established voxel-based lesion mapping techniques and, in the
      future, may potentially be used to estimate impairment and recovery potential
      after stroke and refine inclusion criteria for experimental rehabilitation
      programs.

PMID- 21719774
TI  - Self-expandable stents in the treatment of acute ischemic stroke refractory to
      current thrombectomy devices.
AB  - BACKGROUND AND PURPOSE: Vessel recanalization is a strong predictor of good
      outcome in acute ischemic strokes (AIS) secondary to large vessel occlusions. We
      report our single-center experience with self-expandable stents in the treatment
      of AIS. METHODS: The stroke database of Baptist Cardiac and Vascular Institute in
      Miami was retrospectively reviewed from August of 2008 to September of 2010. All
      cases of AIS in which a self-expandable stents was deployed as acute endovascular
      intervention were included in the analysis. Criteria for intervention were the
      onset of neurological symptoms because of AIS, a National Institute of Health
      Stroke Scale score >=4 at presentation, stroke attributable to a large vessel
      occlusion, and failure of arterial thrombolysis or mechanical thrombectomy or
      both. Good outcome was defined as a modified Rankin Scale score <=2 at 1 month
      from hospital discharge. RESULTS: Nineteen patients with AIS who underwent
      stenting were identified. Median National Institute of Health Stroke Scale score
      on admission was 19. Six Enterprise and 13 Wingspan stents were deployed.
      Recanalization was achieved in 95% occlusions (63% thrombolysis in myocardial
      infarction grade 3 and 32% thrombolysis in myocardial infarction grade 2). Good
      clinical outcome was achieved in 42%. No intraprocedural complications occurred
      and all stents were successfully deployed. Symptomatic intracerebral hemorrhage
      occurred in 3 (16%) patients, 2 of whom died. CONCLUSIONS: Use of self-expandable
      stents in AIS appears to be safe and may be considered when currently available
      thrombectomy devices and/or intraarterial thrombolysis fail.

PMID- 21719775
TI  - Natural vitamin E alpha-tocotrienol protects against ischemic stroke by induction
      of multidrug resistance-associated protein 1.
AB  - BACKGROUND AND PURPOSE: alpha-Tocotrienol (TCT) represents the most potent
      neuroprotective form of natural vitamin E that is Generally Recognized As Safe
      certified by the U.S. Food and Drug Administration. This work addresses a novel
      molecular mechanism by which alpha-TCT may be protective against stroke in vivo.
      Elevation of intracellular oxidized glutathione (GSSG) triggers neural cell
      death. Multidrug resistance-associated protein 1 (MRP1), a key mediator of
      intracellular oxidized glutathione efflux from neural cells, may therefore
      possess neuroprotective functions. METHODS: Stroke-dependent brain tissue damage
      was studied in MRP1-deficient mice and alpha-TCT-supplemented mice. RESULTS:
      Elevated MRP1 expression was observed in glutamate-challenged primary cortical
      neuronal cells and in stroke-affected brain tissue. MRP1-deficient mice displayed
      larger stroke-induced lesions, recognizing a protective role of MRP1. In vitro,
      protection against glutamate-induced neurotoxicity by alpha-TCT was attenuated
      under conditions of MRP1 knockdown; this suggests the role of MRP1 in alpha-TCT
      dependent neuroprotection. In vivo studies demonstrated that oral supplementation
      of alpha-TCT protected against murine stroke. MRP1 expression was elevated in the
      stroke-affected cortical tissue of alpha-TCT-supplemented mice. Efforts to
      elucidate the underlying mechanism identified MRP1 as a target of microRNA (miR)
      199a-5p. In alpha-TCT-supplemented mice, miR-199a-5p was downregulated in stroke
      affected brain tissue. CONCLUSIONS: This work recognizes MRP1 as a protective
      factor against stroke. Furthermore, findings of this study add a new dimension to
      the current understanding of the molecular bases of alpha-TCT neuroprotection in
      2 ways: by identifying MRP1 as a alpha-TCT-sensitive target and by unveiling the
      general prospect that oral alpha-TCT may regulate miR expression in stroke
      affected brain tissue.

PMID- 21719776
TI  - Letter by McColl et al regarding article, "influenza virus infection aggravates
      stroke outcome".

PMID- 21719777
TI  - The influence of comorbidities on overall survival among older women diagnosed
      with breast cancer.
AB  - BACKGROUND: Previous studies have shown that summary measures of comorbid
      conditions are associated with decreased overall survival in breast cancer
      patients. However, less is known about associations between specific comorbid
      conditions on the survival of breast cancer patients. METHODS: The Surveillance,
      Epidemiology, and End Results-Medicare database was used to identify primary
      breast cancers diagnosed from 1992 to 2000 among women aged 66 years or older.
      Inpatient, outpatient, and physician visits within the Medicare system were
      searched to determine the presence of 13 comorbid conditions present at the time
      of diagnosis. Overall survival was estimated using age-specific Kaplan-Meier
      curves, and mortality was estimated using Cox proportional hazards models
      adjusted for age, race and/or ethnicity, tumor stage, cancer prognostic markers,
      and treatment. All statistical tests were two-sided. RESULTS: The study
      population included 64,034 patients with breast cancer diagnosed at a median age
      of 75 years. None of the selected comorbid conditions were identified in 37,306
      (58%) of the 64,034 patients in the study population. Each of the 13 comorbid
      conditions examined was associated with decreased overall survival and increased
      mortality (from prior myocardial infarction, adjusted hazard ratio [HR] of death
      = 1.11, 95% CI = 1.03 to 1.19, P = .006; to liver disease, adjusted HR of death =
      2.32, 95% CI = 1.97 to 2.73, P < .001). When patients of age 66-74 years were
      stratified by stage and individual comorbidity status, patients with each
      comorbid condition and a stage I tumor had similar or poorer overall survival
      compared with patients who had no comorbid conditions and stage II tumors.
      CONCLUSIONS: In a US population of older breast cancer patients, 13 individual
      comorbid conditions were associated with decreased overall survival and increased
      mortality.

PMID- 21719778
TI  - Comorbidities in the aging breast cancer population: are current assessments
      leading to improved outcomes?

PMID- 21719779
TI  - Dual manganese-enhanced and delayed gadolinium-enhanced MRI detects myocardial
      border zone injury in a pig ischemia-reperfusion model.
AB  - BACKGROUND: Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies
      nonviable myocardium but is nonspecific and may overestimate nonviable territory.
      Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into
      viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a
      porcine ischemia-reperfusion (IR) model to test the hypothesis that combined
      DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo.
      METHODS AND RESULTS: Sixty-minute left anterior descending coronary artery IR
      injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI
      was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn(2+) contrast
      agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left
      ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI
      defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were
      analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron
      microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection
      fraction was reduced (30+/-7%). MEMRI and DEMRI infarct volumes correlated with
      2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75;
      P<0.004). MEMRI infarct volume percentage was significantly lower than that of
      DEMRI (14+/-4% versus 23+/-4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was
      intermediate to remote and core infarct SNR (7.5+/-2.8 versus 13.2+/-3.4 and
      2.9+/-1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and
      core infarct SNR (8.4+/-5.4 versus 3.3+/-0.6 and 14.3+/-6.6; P>0.05). Tissue
      electron microscopy analysis exhibited preserved cell structure in BZ
      cardiomyocytes despite transmural DEMRI enhancement. CONCLUSIONS: The dual
      contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This
      approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.

PMID- 21719780
TI  - IL-25 induces M2 macrophages and reduces renal injury in proteinuric kidney
      disease.
AB  - The kidney contains receptors for the cytokine IL-25, but the effects of IL-25 in
      CKD are unknown. Here, we induced adriamycin nephropathy in both BALB/c mice and
      severe combined immunodeficient (SCID) mice, and we injected IL-25 for 7
      consecutive days starting at day 5 after adriamycin administration. BALB/c mice
      treated with IL-25 had less glomerulosclerosis, tubular atrophy, interstitial
      expansion, and proteinuria than control mice at day 28. IL-25 increased the
      levels of IL-4 and IL-13 in serum, kidney, renal draining lymph nodes, and CD4+
      lymphocytes. IL-25 also directly suppressed effector macrophages in vitro and in
      vivo and induced alternatively activated (M2) macrophages in vivo. However, in
      SCID mice and in BALB/c mice treated with IL-4/13-neutralizing antibody, IL-25
      failed to protect against renal injury and did not induce M2. In conclusion, IL
      25 protects against renal injury in adriamycin nephropathy in mice by, at least
      in part, inducing Th2 immune responses.

PMID- 21719781
TI  - Declining renal function in persons of different race without chronic kidney
      disease.

PMID- 21719782
TI  - Parietal epithelial cells participate in the formation of sclerotic lesions in
      focal segmental glomerulosclerosis.
AB  - The pathogenesis of the development of sclerotic lesions in focal segmental
      glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes
      or parietal epithelial cells (PECs) to determine whether PECs contribute to
      sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the
      murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies,
      the primary injury to induce FSGS associated with focal activation of PECs and
      the formation of cellular adhesions to the capillary tuft. From this entry site,
      activated PECs invaded the affected segment of the glomerular tuft and deposited
      extracellular matrix. Within the affected segment, podocytes were lost and
      mesangial sclerosis developed within the endocapillary compartment. In
      conclusion, these results demonstrate that PECs contribute to the development and
      progression of the sclerotic lesions that define FSGS, but this pathogenesis may
      be relevant to all etiologies of glomerulosclerosis.

PMID- 21719783
TI  - Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic
      kidney disease.
AB  - Allopurinol ameliorates endothelial dysfunction and arterial stiffness among
      patients without chronic kidney disease (CKD), but it is unknown if it has
      similar effects among patients with CKD. Furthermore, because arterial stiffness
      increases left ventricular afterload, any allopurinol-induced improvement in
      arterial compliance might also regress left ventricular hypertrophy (LVH). We
      conducted a randomized, double-blind, placebo-controlled, parallel-group study in
      patients with stage 3 CKD and LVH. We randomly assigned 67 subjects to
      allopurinol at 300 mg/d or placebo for 9 months; 53 patients completed the study.
      We measured left ventricular mass index (LVMI) with cardiac magnetic resonance
      imaging (MRI), assessed endothelial function by flow-mediated dilation (FMD) of
      the brachial artery, and evaluated central arterial stiffness by pulse-wave
      analysis. Allopurinol significantly reduced LVH (P=0.036), improved endothelial
      function (P=0.009), and improved the central augmentation index (P=0.015). This
      study demonstrates that allopurinol can regress left ventricular mass and improve
      endothelial function among patients with CKD. Because LVH and endothelial
      dysfunction associate with prognosis, these results call for further trials to
      examine whether allopurinol reduces cardiovascular events in patients with CKD
      and LVH.

PMID- 21719784
TI  - Angiotensin II as a morphogenic cytokine stimulating renal fibrogenesis.
AB  - Inhibitors of the renin-angiotensin-aldosterone system attenuate
      glomerulosclerosis and interstitial fibrosis. Although the mechanisms underlying
      their antifibrotic effects are complex, angiotensin II (Ang II) emerges as a
      major profibrogenic cytokine. Ang II modulates renal cell growth, extracellular
      matrix synthesis, and degradation by multiple fibrotic pathways. One of the main
      targets of Ang II in renal fibrosis is TGFbeta. Many, but not all, of the
      stimulatory effects of Ang II on fibrogenesis depend on the induction of TGFbeta
      and its downstream mediators of matrix accumulation, inflammation, and apoptosis.
      However because of the difficulty in targeting TGFbeta, connective tissue growth
      factor beta (CTGF), a downstream mediator of TGFbeta, has become a more promising
      antifibrotic target. Ang II can directly induce expression of renal CTGF and
      mediate epithelial-mesenchymal transition. Other profibrotic factors stimulated
      by Ang II include endothelin-1, plasminogen activator inhibitor-1, matrix
      metalloproteinase (MMP)-2, and a tissue inhibitor of metalloproteinase-2.
      Finally, connections among Ang II, hypoxia, and the induction of hypoxia
      inducible factor-1alpha contribute to fibrogenesis. A better understanding of the
      multiple morphogenic effects of Ang II may be necessary to develop better
      strategies to halt the progression of renal disease.

PMID- 21719785
TI  - miR-335 and miR-34a Promote renal senescence by suppressing mitochondrial
      antioxidative enzymes.
AB  - The molecular basis for aging of the kidney is not well understood. MicroRNAs
      (miRNAs) contribute to processes such as development, differentiation, and
      apoptosis, but their contribution to the aging process is unknown. Here, we
      analyzed the miRNA expression profile of young (3-month) and old (24-month) rat
      kidneys and identified the biologic pathways and genes regulated by
      differentially expressed miRNAs. We observed upregulation of 18 miRNAs with
      aging, mainly regulating the genes associated with energy metabolism, cell
      proliferation, antioxidative defense, and extracellular matrix degradation; in
      contrast, we observed downregulation of 7 miRNAs with aging, principally
      targeting the genes associated with the immune inflammatory response and cell
      cycle arrest. Bioinformatics analysis suggested that superoxide dismutase 2
      (SOD2) and thioredoxin reductase 2 (Txnrd2), located in the mitochondria, are
      potential targets of miR-335 and miR-34a, respectively. Aging mesangial cells
      exhibited significant upregulation of miR-335 and miR-34a and marked
      downregulation of SOD2 and Txnrd2. miR-335 and miR-34a inhibited expression of
      SOD2 and Txnrd2 by binding to the 3'-untranslated regions of each gene,
      respectively. Overexpression of miR-335 and miR-34a induced premature senescence
      of young mesangial cells via suppression of SOD2 and Txnrd2 with a concomitant
      increase in reactive oxygen species (ROS). Conversely, antisense miR-335 and miR
      34a inhibited senescence of old mesangial cells via upregulation of SOD2 and
      Txnrd2 with a concomitant decrease in ROS. In conclusion, these results suggest
      that miRNAs may contribute to renal aging by inhibiting intracellular pathways
      such as those involving the mitochondrial antioxidative enzymes SOD2 and Txnrd2.

PMID- 21719786
TI  - Podocyte injury damages other podocytes.
AB  - Loss of podocytes promotes glomerulosclerosis, but whether this results from a
      continued primary insult or a secondary mechanism triggered by the initial loss
      of podocytes is unknown. We generated chimeric mice in which only a subpopulation
      of podocytes expressed hCD25, which is the receptor for the immunotoxin LMB2. In
      addition, genetic labeling of hCD25-negative cells with human placental alkaline
      phosphatase allowed the study of these two distinct podocyte populations.
      Administration of LMB2 did not cause podocyte injury in hCD25-negative control
      mice. In contrast, LMB2 severely damaged or sloughed off the subpopulation of
      hCD25-positive podocytes within the chimeric glomeruli. Moreover, hCD25-negative
      podocytes, which were immune to the initial toxin injury, developed injury as
      early as 4 d after LMB2 injection, evidenced by foot process effacement,
      upregulation of desmin, and downregulation of nephrin, podocin, and podocalyxin.
      Furthermore, the magnitude of secondary injury correlated with the magnitude of
      primary injury, supporting the concept of an amplified cascade of podocyte
      injury. In conclusion, podocyte damage can propagate injury by triggering
      secondary damage of "remnant" intact podocytes, even when the primary insult is
      short-lived. This transmission of podocyte injury may form a vicious cycle
      leading to accelerated podocyte deterioration and glomerulosclerosis.

PMID- 21719787
TI  - Small leucine-rich proteoglycans in kidney disease.
AB  - Research over the past 2 decades provides ample evidence that small leucine-rich
      proteoglycans (SLRPs; such as decorin, biglycan, fibromodulin, and lumican) of
      the extracellular matrix are deeply involved in the regulation of inflammatory
      and fibrotic renal disorders. Initial efforts in SLRP research focused on the
      interaction between decorin and TGF-beta because it had been unequivocally
      demonstrated that decorin treatment exerts beneficial effects in fibrotic
      disorders involving TGF-beta overproduction in the kidney. This was followed by a
      paradigm shift in our understanding of SLRP biology, with new evidence showing
      that in addition to their role as structural matrix components, soluble SLRPs
      also act as signaling molecules regulating various complex biologic processes in
      a molecule- and cell-specific manner. With the identification of SLRP-derived
      endogenous ligands of Toll-like receptors, the general question regarding the
      mechanisms of SLRP-derived signaling in pathogen-dependent and independent renal
      inflammation arose. This led to the fascinating concept of SLRPs as autonomous
      triggers of sterile renal inflammation in response to renal stress or injury.
      This review focuses on the key biologic roles of SLRPs in the normal and diseased
      kidney with special emphasis on newly described signaling events triggered by
      these proteoglycans.

PMID- 21719788
TI  - Multiphoton imaging of the functioning kidney.
AB  - Translating discoveries made in isolated renal cells and tubules to the in vivo
      situation requires the assessment of cellular function in intact live organs.
      Multiphoton imaging is a form of fluorescence microscopy that is ideally suited
      to working with whole tissues and organs, but adequately loading cells with
      fluorescence dyes in vivo remains a challenge. We found that recirculation of
      fluorescence dyes in the rat isolated perfused kidney (IPK) resulted in levels of
      intracellular loading that would be difficult to achieve in vivo. This technique
      allowed the imaging of tubular cell structure and function with multiphoton
      microscopy in an intact, functioning organ. We used this approach to follow
      processes in real time, including (1) relative rates of reactive oxygen species
      (ROS) production in different tubule types, (2) filtration and tubular uptake of
      low-molecular-weight dextrans and proteins, and (3) the effects of ischemia
      reperfusion injury on mitochondrial function and cell structure. This study
      demonstrates that multiphoton microscopy of the isolated perfused kidney is a
      powerful technique for detailed imaging of cell structure and function in an
      intact organ.

PMID- 21719789
TI  - Epithelial-to-mesenchymal transition predicts cyclosporine nephrotoxicity in
      renal transplant recipients.
AB  - Maintenance immunosuppression with cyclosporine A (CsA) can cause nephrotoxicity
      in renal transplant recipients. Identifying patients at increased risk for CsA
      nephrotoxicity may allow interventions to prolong graft survival. Here, we
      studied the effect of early CsA withdrawal or maintenance among 96 kidney
      recipients at risk for interstitial fibrosis and tubular atrophy (IF/TA) on the
      basis of tubular expression of vimentin and beta-catenin in a protocol biopsy
      performed 3 months after transplant. In this retrospective analysis of biopsies
      collected during a randomized trial of early withdrawal of CsA or mycophenolate
      mofetil, the semiquantitative score of early phenotypic changes suggestive of
      epithelial-to-mesenchymal transition (EMT) progressed with time among those
      maintained on a CsA-containing regimen. EMT-positive grafts displayed a
      significantly higher IF/TA score and greater progression of the IF/TA score at 12
      months (P=0.001 and 0.008, respectively). EMT-positive grafts exposed to CsA also
      had a greater decrease in estimated GFR compared with EMT-negative grafts exposed
      to CsA and EMT-positive grafts withdrawn from CsA exposure. Multivariable
      analysis revealed that the presence of EMT was an independent risk factor for a
      10% decline in graft function up to 4 years posttransplant (odds ratio 4.49; 95%
      confidence interval 1.02 to 19.9). Collectively, these data demonstrate that
      changes consistent with EMT are strong prognostic biomarkers in renal transplant
      recipients exposed to CsA.

PMID- 21719790
TI  - The inflammatory cytokines TWEAK and TNFalpha reduce renal klotho expression
      through NFkappaB.
AB  - Proinflammatory cytokines contribute to renal injury, but the downstream
      effectors within kidney cells are not well understood. One candidate effector is
      Klotho, a protein expressed by renal cells that has antiaging properties; Klotho
      deficient mice have an accelerated aging-like phenotype, including vascular
      injury and renal injury. Whether proinflammatory cytokines, such as TNF and TNF
      like weak inducer of apoptosis (TWEAK), modulate Klotho is unknown. In mice,
      exogenous administration of TWEAK decreased expression of Klotho in the kidney.
      In the setting of acute kidney injury induced by folic acid, the blockade or
      absence of TWEAK abrogated the injury-related decrease in renal and plasma Klotho
      levels. TWEAK, TNFalpha, and siRNA-mediated knockdown of IkappaBalpha all
      activated NFkappaB and reduced Klotho expression in the MCT tubular cell line.
      Furthermore, inhibition of NFkappaB with parthenolide prevented TWEAK- or
      TNFalpha-induced downregulation of Klotho. Inhibition of histone deacetylase
      reversed TWEAK-induced downregulation of Klotho, and chromatin
      immunoprecipitation showed that TWEAK promotes RelA binding to the Klotho
      promoter, inducing its deacetylation. In conclusion, inflammatory cytokines, such
      as TWEAK and TNFalpha, downregulate Klotho expression through an NFkappaB
      dependent mechanism. These results may partially explain the relationship between
      inflammation and diseases characterized by accelerated aging of organs, including
      CKD.

PMID- 21719791
TI  - Changes in albuminuria predict mortality and morbidity in patients with vascular
      disease.
AB  - The degree of albuminuria predicts cardiovascular and renal outcomes, but it is
      not known whether changes in albuminuria also predict similar outcomes. In two
      multicenter, multinational, prospective observational studies, a central
      laboratory measured albuminuria in 23,480 patients with vascular disease or high
      risk diabetes. We quantified the association between a greater than or equal to
      twofold change in albuminuria in spot urine from baseline to 2 years and the
      incidence of cardiovascular and renal outcomes and all-cause mortality during the
      subsequent 32 months. A greater than or equal to twofold increase in albuminuria
      from baseline to 2 years, observed in 28%, associated with nearly 50% higher
      mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold
      decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR
      0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in
      albuminuria, after adjustment for baseline albuminuria, BP, and other potential
      confounders. Increases in albuminuria also significantly associated with
      cardiovascular death, composite cardiovascular outcomes (cardiovascular death,
      myocardial infarction, stroke, and hospitalization for heart failure), and renal
      outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40;
      95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes
      in albuminuria predict mortality and cardiovascular and renal outcomes,
      independent of baseline albuminuria. This suggests that monitoring albuminuria is
      a useful strategy to help predict cardiovascular risk.

PMID- 21719792
TI  - Diagnosis of IgG4-related tubulointerstitial nephritis.
AB  - IgG4-related systemic disease is an autoimmune disease that was first recognized
      in the pancreas but also affects other organs. This disease may manifest as
      tubulointerstitial nephritis (IgG4-TIN), but its clinicopathologic features in
      the kidney are not well described. Of the 35 patients with IgG4-TIN whose renal
      tissue specimens we examined, 27 (77%) had acute or progressive chronic renal
      failure, 29 (83%) had involvement of other organ systems, and 18 of 23 (78%) had
      radiographic abnormalities. Elevated total IgG or IgG4 serum levels were present
      in 79%. All pathologic specimens featured plasma cell-rich TIN, with most showing
      diffuse, expansile interstitial fibrosis. Immune complexes along the tubular
      basement membranes were present in 25 of 30 (83%). All specimens had a moderate
      to marked increase in IgG4+ plasma cells by immunohistochemistry. We used a
      control group of 175 pathologic specimens with plasma cell-rich interstitial
      infiltrates that can mimic IgG4-TIN to examine the diagnostic utility of IgG4
      immunostaining. Excluding pauci-immune necrotizing and crescentic
      glomerulonephritis, IgG4 immunohistochemistry had a sensitivity of 100% (95% CI
      90-100%) and a specificity of 92% (95% CI 86-95%) for IgG4-TIN. Of the 19
      patients with renal failure for whom treatment and follow-up data were available,
      17 (89%) responded to prednisone. In summary, because no single test definitively
      diagnoses IgG4-related systemic disease, we rely on a combination of histologic,
      immunophenotypic, clinical, radiographic, and laboratory features. When the
      disease manifests in the kidney, our data support diagnostic criteria that can
      distinguish IgG4-TIN from other types of TIN.

PMID- 21719793
TI  - WT1-dependent sulfatase expression maintains the normal glomerular filtration
      barrier.
AB  - Paracrine signaling between podocytes and glomerular endothelial cells through
      vascular endothelial growth factor A (VEGFA) maintains a functional glomerular
      filtration barrier. Heparan sulfate proteoglycans (HSPGs), located on the cell
      surface or in the extracellular matrix, bind signaling molecules such as VEGFA
      and affect their local concentrations, but whether modulation of these moieties
      promotes normal crosstalk between podocytes and endothelial cells is unknown.
      Here, we found that the transcription factor Wilms' Tumor 1 (WT1) modulates VEGFA
      and FGF2 signaling by increasing the expression of the 6-O-endosulfatases Sulf1
      and Sulf2, which remodel the heparan sulfate 6-O-sulfation pattern in the
      extracellular matrix. Mice deficient in both Sulf1 and Sulf2 developed age
      dependent proteinuria as a result of ultrastructural abnormalities in podocytes
      and endothelial cells, a phenotype similar to that observed in children with WT1
      mutations and in Wt1(+/-) mice. These kidney defects associated with a decreased
      distribution of VEGFA in the glomerular basement membrane and on endothelial
      cells. Collectively, these data suggest that WT1-dependent sulfatase expression
      plays a critical role in maintaining the glomerular filtration barrier by
      modulating the bioavailability of growth factors, thereby promoting normal
      crosstalk between podocytes and endothelial cells.

PMID- 21719794
TI  - Gi-coupled gamma-aminobutyric acid-B receptors cross-regulate phospholipase C and
      calcium in airway smooth muscle.
AB  - gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
      mammalian central nervous system, and exerts its actions via both ionotropic
      (GABA(A)) and metabotropic (GABA(B)) receptors. Although the functional
      expression of GABA(B) receptors coupled to the G(i) protein was reported for
      airway smooth muscle, the role of GABA(B) receptors in airway responsiveness
      remains unclear. We investigated whether G(i)-coupled GABA(B) receptors cross
      regulate phospholipase C (PLC), an enzyme classically regulated by G(q)-coupled
      receptors in human airway smooth muscle cells. Both the GABA(B)-selective agonist
      baclofen and the endogenous ligand GABA significantly increased the synthesis of
      inositol phosphate, whereas GABA(A) receptor agonists, muscimol, and 4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol exerted no effect. The baclofen-induced
      synthesis of inositol phosphate and transient increases in [Ca(2+)](i) were
      blocked by CGP35348 and CGP55845 (selective GABA(B) antagonists), pertussis toxin
      (PTX, which inactivates the G(i) protein), gallein (a G(betagamma) signaling
      inhibitor), U73122 (an inhibitor of PLC-beta), and xestospongin C, an inositol
      1,4,5-triphosphate receptor blocker. Baclofen also potentiated the bradykinin
      induced synthesis of inositol phosphate and transient increases in [Ca(2+)](i),
      which were blocked by CGP35348 or PTX. Moreover, baclofen potentiated the
      substance P-induced contraction of airway smooth muscle in isolated guinea pig
      tracheal rings. In conclusion, the stimulation of GABA(B) receptors in human
      airway smooth muscle cells rapidly mobilizes intracellular Ca(2+) stores by the
      synthesis of inositol phosphate via the activation of PLC-beta, which is
      stimulated by G(betagamma) protein liberated from G(i) proteins coupled to
      GABA(B) receptors. Furthermore, crosstalk between GABA(B) receptors and G(q)
      coupled receptors potentiates the synthesis of inositol phosphate, transient
      increases in [Ca(2+)](i), and smooth muscle contraction through G(i) proteins.

PMID- 21719795
TI  - Molecular signature of a right heart failure program in chronic severe pulmonary
      hypertension.
AB  - Right heart failure is the cause of death of most patients with severe pulmonary
      arterial hypertensive (PAH) disorders, yet little is known about the cellular and
      molecular causes of right ventricular failure (RVF). We first showed a
      differential gene expression pattern between normal rat right and left
      ventricles, and postulated the existence of a molecular right heart failure
      program that distinguishes RVF from adaptive right ventricular hypertrophy (RVH),
      and that may differ in some respects from a left heart failure program. By means
      of microarrays and transcriptional sequencing strategies, we used two models of
      adaptive RVH to characterize a gene expression pattern reflective of growth and
      the maintenance of myocardial structure. Moreover, two models of RVF were
      associated with fibrosis, capillary rarefaction, the decreased expression of
      genes encoding the angiogenesis factors vascular endothelial growth factor,
      insulin-like growth factor 1, apelin, and angiopoeitin-1, and the increased
      expression of genes encoding a set of glycolytic enzymes. The treatment of
      established RVF with a beta-adrenergic receptor blocker reversed RVF, and partly
      reversed the molecular RVF program. We conclude that normal right and left
      ventricles demonstrate clearly discernable differences in the expression of mRNA
      and microRNA, and that RVH and RVF are characterized by distinct patterns of gene
      expression that relate to cell growth, angiogenesis, and energy metabolism.

PMID- 21719796
TI  - Physiological response to membrane protein overexpression in E. coli.
AB  - Overexpression represents a principal bottleneck in structural and functional
      studies of integral membrane proteins (IMPs). Although E. coli remains the
      leading organism for convenient and economical protein overexpression, many IMPs
      exhibit toxicity on induction in this host and give low yields of properly folded
      protein. Different mechanisms related to membrane biogenesis and IMP folding have
      been proposed to contribute to these problems, but there is limited understanding
      of the physical and physiological constraints on IMP overexpression and folding
      in vivo. Therefore, we used a variety of genetic, genomic, and microscopy
      techniques to characterize the physiological responses of Escherichia coli MG1655
      cells to overexpression of a set of soluble proteins and IMPs, including
      constructs exhibiting different levels of toxicity and producing different levels
      of properly folded versus misfolded product on induction. Genetic marker studies
      coupled with transcriptomic results indicate only minor perturbations in many of
      the physiological systems implicated in previous studies of IMP biogenesis.
      Overexpression of either IMPs or soluble proteins tends to block execution of the
      standard stationary-phase transcriptional program, although these effects are
      consistently stronger for the IMPs included in our study. However, these
      perturbations are not an impediment to successful protein overexpression. We
      present evidence that, at least for the target proteins included in our study,
      there is no inherent obstacle to IMP overexpression in E. coli at moderate levels
      suitable for structural studies and that the biochemical and conformational
      properties of the proteins themselves are the major obstacles to success.
      Toxicity associated with target protein activity produces selective pressure
      leading to preferential growth of cells harboring expression-reducing and
      inactivating mutations, which can produce chemical heterogeneity in the target
      protein population, potentially contributing to the difficulties encountered in
      IMP crystallization.

PMID- 21719797
TI  - Treatment of infantile spasms: emerging insights from clinical and basic science
      perspectives.
AB  - Infantile spasms is an epileptic encephalopathy of early infancy with specific
      clinical and electroencephalographic (EEG) features, limited treatment options,
      and a poor prognosis. Efforts to develop improved treatment options have been
      hindered by the lack of experimental models in which to test prospective
      therapies. The neuropeptide adrenocorticotropic hormone (ACTH) is effective in
      many cases of infantile spasms, although its mechanism(s) of action is unknown.
      This review describes the emerging candidate mechanisms that can underlie the
      therapeutic effects of ACTH in infantile spasms. These mechanisms can ultimately
      help to improve understanding and treatment of the disease. An overview of
      current treatments of infantile spasms, novel conceptual and experimental
      approaches to infantile spasms treatment, and a perspective on remaining clinical
      challenges and current research questions are presented here. This summary
      derives from a meeting of specialists in infantile spasms clinical care and
      research held in New York City on June 14, 2010.

PMID- 21719798
TI  - Modern perspectives on caries activity and control.

PMID- 21719799
TI  - Children with autism.

PMID- 21719800
TI  - A balanced approach.

PMID- 21719801
TI  - Laser treatment.

PMID- 21719802
TI  - Prevention of prescription opioid abuse: the role of the dentist.
AB  - BACKGROUND: Opioids are analgesics that have potential for misuse, abuse or
      addiction. Up to an estimated 23 percent of prescribed doses are used
      nonmedically. As prescribers of 12 percent of immediate-release (IR) opioids in
      the United States, dentists can minimize the potential for misuse or abuse.
      METHODS: The authors participated in a two-day meeting in March 2010 cohosted by
      Tufts Health Care Institute Program on Opioid Risk Management, Boston, and Tufts
      University School of Dental Medicine, Boston. The purpose of the meeting was to
      synthesize available opioid abuse literature and data from a 2010 survey
      regarding West Virginia dentists' analgesic prescribing practices, identify
      dentists' roles in prescribing opioids that are used nonmedically, highlight
      practices that dentists can implement and identify research gaps. RESULTS:
      Dentists can play a role in minimizing opioid abuse through patient education,
      careful patient assessment and referral for substance abuse treatment when
      indicated, and using tools such as prescription monitoring programs. Research is
      needed to determine the optimal number of doses needed to treat dental-related
      pain. CONCLUSIONS: Dentists cannot assume that their prescribing of opioids does
      not affect the opioid abuse problem in the United States. The authors suggest
      that dentists, along with other prescribers, take steps to identify problems and
      minimize prescription opioid abuse through greater prescriber and patient
      education; use of peer-reviewed recommendations for analgesia; and, when
      indicated, the tailoring of the appropriate and legitimate prescribing of opioids
      to adequately treat pain. Practice Implications. The authors encourage dentists
      to incorporate practical safeguards when prescribing opioids, consistently
      educate patients about how to secure unused opioids properly, screen patients for
      substance use disorders and develop a referral network for the treatment of
      substance use disorders.

PMID- 21719803
TI  - Dental patients' self-reports of xerostomia and associated risk factors.
AB  - BACKGROUND: Most studies regarding xerostomia focus on elderly people. Therefore,
      the authors conducted a study of dental patients 18 years or older to determine
      the prevalence of self-reported xerostomia and associated risk factors. METHODS:
      The authors sent a total of 2,200 questionnaires to four dental clinics to assess
      patients' self-reported xerostomia. They also collected sociodemographic data and
      information regarding personal behavior. They used logistic regression models to
      estimate odds ratios (OR) and 95 percent confidence intervals (CI) to explore the
      relationship between self-reported xerostomia and risk factors that reasonably
      might be expected to be associated with self-reported xerostomia. RESULTS: The
      overall prevalence of xerostomia in participants was 7 percent. Participants with
      burning-mouth sensations were associated with having higher odds of experiencing
      dry mouth (OR, 2.1; 95 percent CI, 0.9-5.2). Participants 51 years or older were
      significantly more likely to report having dry mouth than were younger
      participants (P < .04). The prevalence of self-reported xerostomia increased with
      increasing numbers of medications patients reported using. CONCLUSION: The
      authors found that medication use and age were highly significant risk factors
      for dental patients reporting xerostomia. CLINICAL IMPLICATIONS: Clinicians
      should interview their patients carefully regarding their use of medications and
      provide proper oral health care to improve xerostomia resulting from medication
      use.

PMID- 21719804
TI  - Multifocal oral melanoacanthoma and melanotic macula in a patient after dental
      implant surgery.
AB  - BACKGROUND: Oral melanoacanthoma (OMA) is an uncommon, reactive, pigmented
      mucocutaneous lesion. It is a rapidly growing, well-circumscribed, small, brown
      to-black, solitary or multifocal macule that is characterized histopathologically
      by proliferation of keratinocytes and pigment-laden dendritic melanocytes. CASE
      DESCRIPTION: At the end of a one-month healing period after dental implant
      surgery, a 63-year-old white woman had pigmented lesions at different oral
      mucosal sites (hard palate, buccal mucosa and left maxillary tuberosity) that
      showed macrophages exhibiting iron and melanin in multiple areas of the lamina
      propria. The authors obtained biopsy specimens from all the lesions for
      histologic and immunohistochemical analyses and light-microscopy study.
      CONCLUSIONS AND CLINICAL IMPLICATIONS: Surgery could have been causal or
      incidental to the appearance of these lesions. Clinicians should be aware of this
      possible event and make a correct and pathologically confirmed differential
      diagnosis.

PMID- 21719805
TI  - Diffuse brown pigmentation of the buccal mucosa and tongue.

PMID- 21719806
TI  - Application of etch-and-rinse adhesives on dry and rewet dentin under rubbing
      action: a 24-month clinical evaluation.
AB  - BACKGROUND: Researchers conducting laboratory investigations have reported that
      bonding to dry demineralized dentin can be feasible technically as long as the
      adhesives are rubbed vigorously onto the dentin surface. The authors aimed to
      evaluate the 24-month clinical performance of resin-based composites in
      noncarious cervical lesions (NCCLs) in teeth restored with two etch-and-rinse
      adhesives that had been applied with a vigorous rubbing action to both dry and
      rewet dentin. METHODS: The authors enrolled 40 patients in this study. They
      inserted 160 restorations and evaluated them at baseline and at six, 12 and 24
      months of service. They divided the restorations into four groups: One-Step (OS)
      Universal Dental Adhesive System (Bisco, Schaumburg, Ill.) (acetone-based
      adhesive) with rewet dentin; OS with dry dentin; Adper Single Bond (SB) Plus
      Adhesive (3M ESPE, St. Paul, Minn.) (ethanol/water-based adhesive) with rewet
      dentin; and SB with dry dentin. The authors used the same resin-based composite
      for all restorations. They evaluated the restorations according to modified U.S.
      Public Health Service criteria. RESULTS: The 24-month retention rates for the
      rewet and dry conditions, respectively, were 95.0 percent and 97.5 percent for SB
      and 97.5 percent and 91.9 percent for OS. The authors detected no significant
      difference between rewet and dry groups for either adhesive (P > .05). In terms
      of marginal discoloration, OS performed significantly worse than did SB,
      irrespective of dentin moisture (P > .05). CONCLUSIONS AND CLINICAL IMPLICATIONS:
      Dentin moisture seems not to be important for the retention of etch-and-rinse
      adhesives as long as the adhesives have been rubbed vigorously onto the dentin
      surface. The ethanol/water-based adhesive showed a better overall performance
      than did the acetone-based system.

PMID- 21719807
TI  - Assessing the use of 35 percent sodium ascorbate for removal of residual hydrogen
      peroxide after in-office tooth bleaching.
AB  - BACKGROUND: The authors conducted a study to quantify the amount of hydrogen
      peroxide remaining after in-office bleaching and to investigate the effectiveness
      of 35 percent sodium ascorbate (SA) on removal of the bleaching agent from
      dentin. METHODS: The authors sectioned 70 extracted human third molars to form
      4*4*2-millimeter blocks of dentin and then categorized them into eight groups as
      follows: group 1, no bleaching; group 2, bleaching (35 percent hydrogen peroxide)
      and daily measurement; group 3, bleaching plus one application of 35 percent SA
      for 60 minutes; group 4, bleaching plus one application of SA for 10 minutes;
      group 5, bleaching plus two applications of SA for 10 minutes each; group 6,
      bleaching plus two applications of SA for five minutes each; group 7, bleaching
      plus three applications of SA for one minute each; and group 8, bleaching plus
      two applications of SA for one minute each. They quantified the amount of
      residual hydrogen peroxide by using a colorimetric assay with horseradish
      peroxidase and o-phenylenediamine dihydrochloride as the enzyme and substrate,
      respectively. RESULTS: The authors analyzed the data by using the Kruskal-Wallis
      test (alpha = .05). The results showed that no hydrogen peroxide remained after
      120 hours in group 2 and at their respective measurement points in groups 5, 6, 7
      and 8, whereas hydrogen peroxide had been removed only partially in groups 3 and
      4. CONCLUSION: Two applications of 35 percent SA for one minute each produced the
      same result--complete removal of the bleaching agent--as that observed five days
      after tooth bleaching with 35 percent hydrogen peroxide without any application
      of SA. CLINICAL IMPLICATIONS: In an appropriate concentration, SA facilitates
      rapid elimination of residual peroxide up to two minutes after bleaching with 35
      percent hydrogen peroxide. This finding suggests that clinicians can perform
      bonding procedures shortly after the bleaching procedure.

PMID- 21719808
TI  - Alternative treatments to replacement of defective amalgam restorations: results
      of a seven-year clinical study.
AB  - BACKGROUND: The authors conducted a prospective cohort clinical study to
      investigate the effectiveness of alternative treatments to the replacement of
      defective amalgam restorations. METHODS: Fifty patients aged 21 through 77 years
      (mean age, 56 years) with 113 defective amalgam restorations that were diagnosed
      during treatment planning participated in the study. The authors assigned each
      tooth to one of five treatment groups: repair with amalgam (n = 20), sealing of
      defective margins (n = 23), refinishing (n = 23), replacement (n = 22) or no
      treatment (n = 25). The replacement and no-treatment groups served as comparison
      groups, and the authors assigned 47 teeth randomly to these groups. Two
      clinicians examined the restorations before and after the assigned treatment and
      at subsequent recall visits by using modified U.S. Public Health Service criteria
      including marginal adaptation, anatomic form, occlusal and proximal contact,
      postoperative sensitivity and secondary caries. RESULTS: The clinicians examined
      94 restorations (83 percent) at the one-year recall visit, 74 (65 percent) at the
      two-year recall visit and 54 (48 percent) at the seven-year recall visit. They
      observed most of the downgraded and failed restorations after the first two years
      of clinical service. CONCLUSIONS: The study results show that some degree of
      degradation occurred in all treatment groups, including the replacement group, at
      the seven-year recall examination, with no significant failure rate. The results
      support the repair of defective amalgam restorations as an alternative to
      replacement. Furthermore, the study findings show that in future controlled
      clinical trials, all teeth may receive random assignment. CLINICAL IMPLICATIONS:
      The study findings support repair rather than replacement of amalgam restorations
      with localized defects. Randomized controlled trials are needed to confirm these
      findings.

PMID- 21719809
TI  - Periodontal plastic surgery procedures reduce localized gingival recession
      defects.

PMID- 21719810
TI  - Building better team morale.

PMID- 21719811
TI  - Is it unethical to have a policy for medicaid-enrolled patients that allows
      termination of the relationship when the patient does not show up or call?

PMID- 21719812
TI  - Oral health during cancer treatment.

PMID- 21719813
TI  - Hematologic, plasma biochemical, and other indicators of the health of Tasmanian
      platypuses (Ornithorhynchus anatinus): predictors of mucormycosis.
AB  - The fungal disease mucormycosis has affected Tasmanian platypuses for nearly
      three decades. We investigated the influences of mucormycosis on the hematologic,
      plasma biochemical, and other indicators of health in free-living platypuses
      across 18 Tasmanian river catchments. Live trapping enabled sampling of 161
      (apparently) healthy and six ulcerated, mucormycosis-affected platypuses in 75
      rivers and streams between January 2008 and June 2009. There were no obvious
      differences in any hematologic or biochemical measures between healthy and
      mucormycosis-affected platypuses. However, multivariate analysis revealed that
      ulceration was associated with living at higher altitudes, low tail fat content
      (high tail fat index), and low trypanosome load. There was evidence of overall
      lymphocytosis and monocytosis in animals from areas currently affected by
      mucormycosis, which suggests that some level of immune response to the introduced
      fungus is now widespread in disease-affected catchments. Animals from currently,
      historically, and possibly disease-affected catchments had lower neutrophil
      counts, mean cell volumes, plasma alkaline phosphatase, alanine aminotransferase,
      and aspartate aminotransferase levels, and higher plasma gamma-glutamyl
      transpeptidase and platelet counts compared to animals from catchments with no
      evidence of infection. Reference intervals were generated for all hematologic and
      biochemical measurements. Since this is the most comprehensive, systematic, and
      large-scale assessment of the health of the Tasmanian platypus to date, these
      references intervals should act as the standard against which future studies of
      platypuses in Tasmania should be compared.

PMID- 21719814
TI  - Inbreeding depression increases susceptibility to bovine tuberculosis in lions:
      an experimental test using an inbred-outbred contrast through translocation.
AB  - Disease can dramatically influence the dynamics of endangered wildlife
      populations, especially when they are small and isolated, with increased risk of
      inbreeding. In Hluhluwe-iMfolozi Park (HiP), a small, enclosed reserve in South
      Africa, a large lion (Panthera leo) population arose from a small founder group
      in the 1960s and started showing conspicuous signs of inbreeding. To restore the
      health status of the HiP lion population, outbred lions were translocated into
      the existing population. In this study, we determined the susceptibility to
      bovine tuberculosis (bTB), and the prevalence of antibody to feline viruses of
      native lions, and compared the findings with those from translocated outbred
      lions and their offspring. Antibodies to feline herpesvirus, feline calicivirus,
      feline parvovirus, and feline coronavirus were present in the lion population,
      but there was no significant difference in antibody prevalence between native and
      translocated lions and their offspring, and these feline viruses did not appear
      to have an effect on the clinical health of HiP lions. However, feline
      immunodeficiency virus (FIV), which was previously absent from HiP, appears to
      have been introduced into the lion population through translocation. Within 7 yr,
      the prevalence of antibody to FIV increased up to 42%. Bovine tuberculosis posed
      a major threat to the inbred native lion population, but not to translocated
      lions and their offspring. More than 30% of the native lion population died from
      bTB or malnutrition compared with <2% of the translocated lions and their
      offspring. We have demonstrated that management of population genetics through
      supplementation can successfully combat a disease that threatens population
      persistence. However, great care must be taken not to introduce new diseases into
      populations through translocation.

PMID- 21719815
TI  - DNA vaccination of bison to brucellar antigens elicits elevated antibody and IFN
      gamma responses.
AB  - Brucella abortus remains a threat to the health and well-being of livestock in
      states bordering the Greater Yellowstone Area. During the past several years,
      cohabitation of infected wildlife with cattle has jeopardized the brucellosis
      free status of Idaho, USA; Wyoming, USA; and Montana, USA. Current livestock B.
      abortus vaccines have not proven to be efficacious in bison (Bison bison) or elk
      (Cervus elaphus nelsoni). One problem with the lack of vaccine efficacy may stem
      from the failure to understand wildlife immune responses to vaccines. In an
      attempt to understand their immune responses, bison were vaccinated with
      eukaryotic DNA expression vectors encoding the Brucella periplasmic protein,
      bp26, and the chaperone protein, trigger factor (TF). These DNA vaccines have
      previously been shown to be protective against Brucella infection in mice. Bison
      were immunized intramuscularly at weeks 0, 2, and 4 with bp26 and TF DNA vaccines
      plus CpG adjuvant or empty vector (control) plus CpG. Blood samples were
      collected before vaccination and at 8, 10, and 12 wk after primary vaccination.
      The results showed that bison immunized with bp26 and TF DNA vaccines developed
      enhanced antibody, proliferative T cell, and interferon-gamma (IFN-gamma)
      responses upon in vitro restimulation with purified recombinant bp26 or TF
      antigens, unlike bison immunized with empty vector. Flow cytometric analysis
      revealed that the percentages of CD4(+) and CD8(+) T lymphocytes from the DNA
      vaccinated groups were significantly greater than they were for those bison given
      empty vector. These data suggest that DNA vaccination of bison may elicit strong
      cellular immune responses and serve as an alternative for vaccination of bison
      for brucellosis.

PMID- 21719816
TI  - Hematologic and plasma biochemical reference intervals for Morelet's crocodiles
      (Crocodylus moreletii) in the northern wetlands of Campeche, Mexico.
AB  - Health surveys and hematologic and plasma biochemical analyses were conducted in
      52 free-ranging and 51 captive Morelet's crocodiles (Crocodylus moreletii) in
      Campeche, Mexico, March-September 2007. Blood samples from 92 crocodiles (45 free
      ranging and 47 captive) were collected for hematologic and plasma biochemical
      analyses. Average values of erythrocytes of free-ranging crocodiles were
      1,046,166 cells/MUl, and total white cells were 1.03 * 10(4) cells/MUl. Captive
      crocodiles had erythrocyte and leukocyte values of 1,100,416 cells/MUl and 8.51 *
      10(3) cells/MUl, respectively. There were no significant differences in values of
      erythrocytes or in hematocrit between free-ranging and captive crocodiles, or
      between sexes, or among size classes. Counts of leukocytes in free-ranging
      crocodiles were significantly higher than in captive individuals. The mean values
      of plasma analytes were 69.55 mg/l (glucose), 250.14 mg/l (cholesterol), 3.04
      mg/l (uric acid), 2.70 mg/l (creatinine), and 20.20 IU/l (alanine
      aminotransferase). There were significant differences in cholesterol between free
      ranging and captive crocodiles and between sexes.

PMID- 21719817
TI  - Blood biochemistry reference values for wild juvenile loggerhead sea turtles
      (Caretta caretta) from Madeira archipelago.
AB  - Standard biochemical parameters were determined in wild juvenile loggerhead sea
      turtles Caretta caretta living offshore Madeira Island, northeast Atlantic. We
      analyzed the influence of age, sex, sea surface temperature, and body condition
      index on biochemical parameters including uric acid, total bilirubin, total
      cholesterol, creatinine kinase (CK), glucose, total protein, urea nitrogen,
      lactate dehydrogenase, aspartate aminotranspherase (AST), gamma-glutamyl
      transferase (GGT), albumin, alkaline phosphatase (ALP), sodium (NA), potassium
      (K), chloride, calcium, phosphorus, and magnesium. Significant positive
      correlations were found between turtle body size and total cholesterol, total
      protein, and albumin. Total protein and the enzymes AST and CK were lower than
      reported levels in adults. Calcium levels were lower than those reported in adult
      or captive turtles, but similar to wild juveniles from Australian waters, and
      were interpreted as normal for this age category. These data may be useful to
      evaluate the health status of stranded or injured animals and to improve
      veterinary care at rehabilitation centers.

PMID- 21719818
TI  - Epizootiologic investigations of selected abortive agents in free-ranging Alpine
      ibex (Capra ibex ibex) in Switzerland.
AB  - In the early 2000s, several colonies of Alpine ibex (Capra ibex ibex) in
      Switzerland ceased growing or began to decrease. Reproductive problems due to
      infections with abortive agents might have negatively affected recruitment. We
      assessed the presence of selected agents of abortion in Alpine ibex by serologic,
      molecular, and culture techniques and evaluated whether infection with these
      agents might have affected population densities. Blood and fecal samples were
      collected from 651 ibex in 14 colonies throughout the Swiss Alps between 2006 and
      2008. All samples were negative for Salmonella spp., Neospora caninum, and Bovine
      Herpesvirus-1. Antibodies to Coxiella burnetii, Leptospira spp., Chlamydophila
      abortus, Toxoplasma gondii, and Bovine Viral Diarrhea virus were detected in at
      least one ibex. Positive serologic results for Brucella spp. likely were false.
      Overall, 73 samples (11.2%) were antibody-positive for at least one abortive
      agent. Prevalence was highest for Leptospira spp. (7.9%, 95% CI=5.0-11.7). The
      low prevalences and the absence of significant differences between colonies with
      opposite population trends suggest these pathogens do not play a significant role
      in the population dynamics of Swiss ibex. Alpine ibex do not seem to be a
      reservoir for these abortive agents or an important source of infection for
      domestic livestock in Switzerland. Finally, although interactions on summer
      pastures occur frequently, spillover from infected livestock to free-ranging ibex
      apparently is uncommon.

PMID- 21719819
TI  - Prevalence of Batrachochytrium dendrobatidis in Agalychnis moreletii (Hylidae) of
      El Salvador and association with larval jaw sheath depigmentation.
AB  - Amphibian populations around the world have been declining at an alarming rate
      due to factors such as habitat destruction, pollution, and infectious diseases.
      Between May and July 2008, we investigated a fungal pathogen in the critically
      endangered Morelet's treefrog (Agalychnis moreletii) at sites in El Salvador.
      Larvae were screened with a hand lens for indications of infection with
      Batrachochytrium dendrobatidis (Bd), a fungus that can cause lethal
      chytridiomycosis in amphibians. Subsets of inspected tadpoles were preserved for
      analysis by polymerase chain reaction to determine the effectiveness of hand lens
      screening for presence of Bd and to estimate infection prevalence at various
      sites. Because individuals with signs of infection were preferentially included,
      we used a novel method to generate unbiased estimates of infection prevalence
      from these biased samples. External mouthpart deformities, identified with a hand
      lens, successfully predicted Bd infection across a large spatial scale. Two of 13
      sites sampled had high (>= 89%) estimated prevalence, whereas little or no Bd was
      detected at the remaining sites. Although it appears that A. moreletii
      populations in this region are not suffering rapid declines due to Bd, further
      monitoring is required to determine the extent to which these populations are
      stably coexisting with the pathogen.

PMID- 21719820
TI  - Serologic survey for potential pathogens and assessment of disease risk in
      Australian fur seals.
AB  - The introduction of pathogens into populations of animals with no previous
      exposure to them and, therefore, no immunologic protection, can result in
      epizootics. Predicting the susceptibility of populations to infectious diseases
      is crucial for their conservation and management. Australian fur seals
      (Arctocephalus pusillus doriferus) have a relatively small population size, a
      restricted range, and form dense aggregations. These factors make this species
      vulnerable to epizootics of infectious diseases that spread by direct animal-to
      animal contact. Blood samples were collected from 125 adult female Australian fur
      seals between 2007 and 2009 and tested for exposure to selected pathogens. The
      testing protocol was based on pathogens important to marine mammal health or
      those significant to public and livestock health. No antibodies were detected to
      morbilliviruses, influenza A viruses, six Leptospira serovars, Mycobacterium
      tuberculosis-complex species, or Toxoplasma gondii. Overall antibody prevalence
      to an unidentified Brucella sp. was 57% but varied significantly (P<0.02) between
      2007 (74%) and 2008 (53%). The findings indicate Brucella infection may be
      enzootic in the Australian fur seal population. Further investigations are
      required to isolate the bacteria and establish if infection results in morbidity
      and mortality. Australian fur seals remain vulnerable to the threat of introduced
      disease and should be managed and monitored accordingly.

PMID- 21719821
TI  - Avian influenza shedding patterns in waterfowl: implications for surveillance,
      environmental transmission, and disease spread.
AB  - Despite the recognized importance of fecal/oral transmission of low pathogenic
      avian influenza (LPAI) via contaminated wetlands, little is known about the
      length, quantity, or route of AI virus shed by wild waterfowl. We used published
      laboratory challenge studies to evaluate the length and quantity of low
      pathogenic (LP) and highly pathogenic (HP) virus shed via oral and cloacal routes
      by AI-infected ducks and geese, and how these factors might influence AI
      epidemiology and virus detection. We used survival analysis to estimate the
      duration of infection (from virus inoculation to the last day virus was shed) and
      nonlinear models to evaluate temporal patterns in virus shedding. We found higher
      mean virus titer and longer median infectious period for LPAI-infected ducks (10
      11.5 days in oral and cloacal swabs) than HPAI-infected ducks (5 days) and geese
      (7.5 days). Based on the median bird infectious dose, we found that environmental
      contamination is two times higher for LPAI- than HPAI-infectious ducks, which
      implies that susceptible birds may have a higher probability of infection during
      LPAI than HPAI outbreaks. Less environmental contamination during the course of
      infection and previously documented shorter environmental persistence for HPAI
      than LPAI suggest that the environment is a less favorable reservoir for HPAI.
      The longer infectious period, higher virus titers, and subclinical infections
      with LPAI viruses favor the spread of these viruses by migratory birds in
      comparison to HPAI. Given the lack of detection of HPAI viruses through worldwide
      surveillance, we suggest monitoring for AI should aim at improving our
      understanding of AI dynamics (in particular, the role of the environment and
      immunity) using long-term comprehensive live bird, serologic, and environmental
      sampling at targeted areas. Our findings on LPAI and HPAI shedding patterns over
      time provide essential information to parameterize environmental transmission and
      virus spread in predictive epizootiologic models of disease risks.

PMID- 21719822
TI  - Assessment of clinical pathology and pathogen exposure in sea otters (Enhydra
      lutris) bordering the threatened population in Alaska.
AB  - Northern sea otter (Enhydra lutris kenyoni) abundance has decreased dramatically
      over portions of southwest Alaska, USA, since the mid-1980s, and this stock is
      currently listed as threatened under the Endangered Species Act. In contrast,
      adjacent populations in south central Alaska, USA, and Russia have been stable to
      increasing during the same period. Sea otters bordering the area classified in
      the recent decline were live-captured during 2004-2006 at Bering Island, Russia,
      and the Kodiak Archipelago, Alaska, USA, to evaluate differences in general
      health and current exposure status to marine and terrestrial pathogens. Although
      body condition was lower in animals captured at Bering Island, Russia, than it
      was at Kodiak, USA, clinical pathology values did not reveal differences in
      general health between the two regions. Low prevalences of antibodies (<5%) were
      found in Kodiak, USA, and on Bering Island, Russia, to Toxoplasma gondii,
      Sarcocystis neurona, and Leptospira interrogans. Exposure to phocine herpesvirus
      1 was found in both Kodiak, USA (15.2%), and Bering Island, Russia (2.3%).
      Antibodies to Brucella spp. were found in 28% of the otters tested on Bering
      Island, Russia, compared with only 2.7% of the samples from Kodiak, USA.
      Prevalence of exposure to Phocine distemper virus (PDV) was 41% in Kodiak, USA,
      but 0% on Bering Island, Russia. Archived sera from southwest and south-central
      Alaska dating back to 1989 were negative for PDV, indicating exposure occurred in
      sea otters in Kodiak, USA, in recent years. Because PDV can be highly pathogenic
      in naive and susceptible marine mammal populations, tissues should be examined to
      explore the contribution of this virus to otter deaths. Our results reveal an
      increase in exposure to pathogens in sea otters in Kodiak, Alaska, USA, since the
      1990 s.

PMID- 21719823
TI  - Oral vaccination against raccoon rabies: landscape heterogeneity and timing of
      distribution influence wildlife contact rates with the ONRAB vaccine bait.
AB  - Aerial distribution of oral vaccine baits is one of the available strategies for
      controlling the spread of infectious wildlife diseases. This technique has
      commonly been used to control rabies in wild carnivores and, together with other
      techniques, was used to immunize wild populations of raccoons (Procyon lotor) and
      striped skunks (Mephitis mephitis) after the detection of the first rabid raccoon
      in the province of Quebec, Canada, in 2006. Vaccine bait distribution was
      conducted over large areas where agricultural land is dominant but interspersed
      with residual forest patches. Our objective was to evaluate the effect of habitat
      (forest vs. agricultural crops) in space and time on the contact rate between
      wildlife and the ONRAB((r)) vaccine bait, a recent alternative to the V-RG((r)).
      Four transects of eight vaccine baits each were installed parallel to, and at
      different distances from, the forest's edge (under forest cover, at field-forest
      edge, and at 50 and 200 m from forest edge in agricultural crops) at three sites
      composed of various crop types interspersed with forest patches. This experiment
      was conducted during three periods (late spring, 1-7 June; summer, 27 July-2
      August; and fall, 24-30 October) in 2009. Contact rates with vaccine baits were
      monitored for 7 days in each period to evaluate the potential temporal variations
      generated within the habitat types. Contact rates with ONRAB vaccine baits were
      highest under forest cover and in the fall. Of 13 species observed in proximity
      to the vaccine baits, raccoons were the most frequent (49.5%, n=55 visits). Our
      study underlines the importance of taking into account landscape heterogeneity
      and timing of distribution when planning the distribution of vaccine baits to
      control rabies in raccoons.

PMID- 21719824
TI  - Field investigation of innate immunity in passerine birds in suburban Chicago,
      Illinois, USA.
AB  - The innate immune system is the first line of defense against pathogens, and it
      plays a fundamental role in coordinating a protective immune response in birds.
      Although many studies have evaluated avian immune responses in the laboratory,
      many fewer studies to date have done so in a field setting. To gain insight into
      interspecific differences in immune function in wild birds, we used a field
      deployed in vitro microbicidal assay to measure constitutive innate immunity of
      whole blood collected from three common passerines in suburban Chicago, Illinois,
      in 2009. Data from one microbe, Escherichia coli 8739, revealed that American
      Robins (Turdus migratorius) had significantly lower bactericidal capacity than
      House Sparrows (Passer domesticus) or Gray Catbirds (Dumetella carolinensis).
      Bactericidal capacity for E. coli 8739 tended to be lower for birds infested with
      chewing lice than those without chewing lice, and male birds had lower
      microbicidal capacity than females in the case of Staphylococcus aureus. This
      study demonstrates the potential for field-deployable eco-immunologic tools to
      inform infectious disease ecology research.

PMID- 21719825
TI  - Chiggers recently infesting Spea spp. in Texas, USA, were Eutrombicula
      alfreddugesi, not Hannemania sp.
AB  - Upon re-examination of preserved larval chiggers collected from spadefoot toads
      (Spea bombifrons and Spea multiplicata) in the Southern High Plains of Texas,
      USA, and identified previously as Hannemania sp., we found them to be
      Eutrombicula alfreddugesi. A review of previous reports of Eutrombicula spp.
      chiggers on amphibian hosts provides context for current findings. All members of
      the genus Hannemania are specialized larval parasites of amphibians, whereas
      larval E. alfreddugesi are generalist parasites of a wide variety of terrestrial
      vertebrate hosts that infrequently includes amphibians. Spadefoot toads are
      previously undocumented hosts for E. alfreddugesi, and observed infestations were
      unusually prevalent and intense for this chigger on an amphibian host.

PMID- 21719826
TI  - Recovery of little brown bats (Myotis lucifugus) from natural infection with
      Geomyces destructans, white-nose syndrome.
AB  - Geomyces destructans produces the white fungal growth on the muzzle and the tacky
      white discoloration on wings and ears that characterize white-nose syndrome (WNS)
      in cave-hibernating bats. To test the hypothesis that postemergent WNS-infected
      bats recover from infection with G. destructans, 30 little brown bats (Myotis
      lucifugus) were collected in May 2009 from a WNS-affected hibernation site in New
      Jersey. All bats were confirmed to be infected with G. destructans using a
      noninvasive fungal tape method to identify the conidia of G. destructans and
      polymerase chain reaction (PCR). The bats were then held in captivity and given
      supportive care for 70 days. Of the 26 bats that survived and were humanely
      killed after 70 days, 25 showed significant improvement in the external
      appearance of wing membranes, had no microscopic evidence of infection by G.
      destructans, and had wing tissue samples that were negative for G. destructans by
      PCR. A subset of the bats was treated topically at the beginning of the
      rehabilitation study with a dilute vinegar solution, but treatment with vinegar
      provided no added advantage to recovery. Provision of supportive care to
      homeothermic bats was sufficient for full recovery from WNS. One bat at day 70
      still had both gross pathology and microscopic evidence of WNS in wing membranes
      and was PCR-positive for G. destructans. Dense aggregates of neutrophils
      surrounded the hyphae that remained in the wing membrane of this bat.

PMID- 21719827
TI  - Mortality factors and diseases in free-ranging Eurasian cranes (Grus grus) in
      Germany.
AB  - Detailed postmortem examinations were performed on 167 free-ranging Eurasian
      Cranes (Grus grus) from Germany, collected between September 1998 and December
      2008 to evaluate causes of death and diseases. The most common causes of
      mortality were traumatic injuries (n=105, 62.9%) from collisions with power lines
      (n=39, 23.4%) and wire fences (n=12, 7.2%). A group of 28 Eurasian Cranes (16.8%)
      died from organophosphate intoxication. Predation by White-tailed Sea Eagles
      (Haliaeetus albicilla) and red foxes (Vulpes vulpes) occurred in four cases
      (2.4%). Pathologic changes due to infectious diseases were associated with
      Aspergillus spp. (n=7, 4.2%), endoparasites (n=7, 4.2%), avian poxvirus (n=6,
      3.6%), Mycobacterium spp. (n=2, 1.2%), and adenovirus infection (n=1, 0.6%). A
      severe Strigea spp. infection (n=1, 0.6%) and a leiomyosarcoma (n=1, 0.6%) were
      newly recognized diseases in Eurasian Cranes in this study.

PMID- 21719828
TI  - Sufentanil and xylazine immobilization of Rocky Mountain elk.
AB  - From October 2009 through July 2010, five captive, 3-yr-old, female Rocky
      Mountain elk (Cervus elaphus) and nine free-ranging elk (one male, eight female)
      were immobilized with 0.1 mg/kg sufentanil plus 0.5 mg/kg xylazine which was
      antagonized with 1 mg/kg naltrexone and 2 mg/kg tolazoline. Induction and
      recovery times averaged 4.9 +/- 0.3 min and 3.9 +/- 0.4 min, respectively.
      Physiologic and blood gas parameters as well as bispectral index (BIS) were
      measured on the captive elk every 10 min for 30 min. Immobilization induced
      profound hypoxemia via hypoventilation and ventilation-perfusion mismatching as
      demonstrated by depressed partial pressure of arterial oxygen (P(a)O(2)) and
      increased partial pressure of arterial carbon dioxide (P(a)CO(2)). The only
      values to significantly (P<0.05) change over time were base excess (BE),
      bicarbonate (HCO(3)), and lactate. Bispectral index is a measure of anesthetic
      depth. The average BIS value over the 30 min period (59.1 +/- 2.4) was higher
      than the BIS value at the approximate point where elk lose consciousness, which
      indicated that this drug combination produced neuroleptanalgesia but not general
      anesthesia. Sufentanil and xylazine provided effective remote immobilization in
      elk and could be substituted for carfentanil or thiafentanil and xylazine should
      the need arise.

PMID- 21719829
TI  - Pharmacokinetics of moxidectin in the southern hairy-nosed wombat (Lasiorhinus
      latifrons).
AB  - Sarcoptic mange, caused by Sarcoptes scabiei var. wombati, could be a significant
      threat to populations of southern hairy-nosed wombats (Lasiorhinus latifrons;
      SHNW) in Australia. Treatment is currently based on the off-label use of various
      parasiticidal drugs, with limited clinical efficacy trials. Our primary aim was
      to determine the pharmacokinetic parameters of a macrocyclic lactone, moxidectin,
      to assist in the development of effective treatment protocols. Pharmacokinetic
      parameters were determined in four female SHNW following a single subcutaneous
      injection of 0.2 mg/kg moxidectin. Blood samples were collected for 38 days
      following injection (August-September 2008), for analysis using liquid
      chromatography and tandem mass spectrometry. The mean peak plasma concentration
      occurred at 13.6 hr, with a mean peak plasma level of 98.6 ng/ml. The mean
      elimination half-life was 5.03 days, resulting in a mean area under the curve of
      377 ng.day/ml. The peak plasma moxidectin concentration was higher than that seen
      in livestock species but the plasma elimination half-life was shorter. This study
      suggests that a single injection of 0.2 mg/kg moxidectin may not be sufficient to
      clear a mange infection in this species.

PMID- 21719830
TI  - Adverse health effects in Canada geese (Branta canadensis) associated with waste
      from zinc and lead mines in the Tri-State Mining District (Kansas, Oklahoma, and
      Missouri, USA).
AB  - Lead and zinc poisoning have been recorded in a variety of bird species,
      including migrating waterfowl such as Canada Geese (Branta canadensis), at sites
      contaminated with mine waste from lead and zinc mines in the Tri-State Mining
      District, Kansas, Oklahoma, and Missouri, USA. The adverse health impacts from
      mine waste on these birds may, however, be more extensive than is apparent from
      incidental reports of clinical disease. To characterize health impacts from mine
      waste on Canada Geese that do not have observable signs of poisoning, four to
      eight apparently healthy birds per site were collected from four contaminated
      sites and an uncontaminated reference site, and examined for physical and
      physiologic evidence of metals poisoning. Tissue concentrations of silver,
      aluminum, arsenic, barium, cadmium, cobalt, chromium, copper, iron, magnesium,
      manganese, molybdenum, nickel, lead, selenium, thallium, vanadium, and zinc were
      determined by inductively coupled plasma mass spectroscopy. Adverse health
      effects due to lead were characterized by assessing blood delta-aminolevulinic
      acid dehydratase (ALAD) enzyme activity. Adverse effects associated with zinc
      poisoning were determined from histologic examination of pancreas tissues.
      Elevated tissue lead concentrations and inhibited blood ALAD enzyme activities
      were consistently found in birds at all contaminated sites. Histopathologic signs
      of zinc poisoning, including fibrosis and vacuolization, were associated with
      elevated pancreatic zinc concentrations at one of the study sites. Adverse health
      effects associated with other analyzed elements, or tissue concentrations
      indicating potentially toxic exposure levels to these elements, were not
      observed.

PMID- 21719831
TI  - A comparative study of hepatic trace element levels in wild moose, roe deer, and
      reindeer from Norway.
AB  - Liver samples from 422 wild moose (Alces alces), 280 roe deer (Capreolus
      capreolus), and 73 reindeer (Rangifer tarandus) collected by hunters in various
      localities in Norway, 2002-2003, were analyzed for the essential trace elements
      cobalt, copper (Cu), manganese (Mn), molybdenum, selenium (Se), and zinc.
      Significant differences in hepatic concentrations among species were found for
      all elements except for Mn, and considerable individual and geographic variations
      were seen. Roe deer had statistically significant lower Se levels (median: 0.51
      MUg Se/g dry weight) than did moose (0.77 MUg Se/g) and reindeer (0.85 MUg Se/g).
      Moose from two coastal municipalities with high precipitation had considerably
      higher Se concentrations than those from the other localities studied. Seventy
      nine roe deer (28%) and 36 moose (9%) had Se concentrations below that regarded
      as deficient in domestic ruminants. The Se status in roe deer was lower than
      previously reported in Europe. Moose had a significantly higher Cu (222 MUg Cu/g
      dw) than did roe deer (112 MUg Cu/g) and reindeer (105 MUg Cu/g). The Cu status
      of moose and roe deer in Norway are among the highest reported in Europe.
      However, a suboptimal Se and Cu status was found in moose from Tvedestrand, a
      population which has suffered from a reduced condition and productivity. The
      variability in trace element status among hunted cervids, with no apparent signs
      of deficiency or toxicity, probably reflects adaptations in these wild ruminant
      species to cope with this. However, subtle clinical signs and lesions are
      difficult to detect and further research is needed.

PMID- 21719832
TI  - Seroepidemiology of TmPV1 infection in captive and wild Florida manatees
      (Trichechus manatus latirostris).
AB  - In 1997, cutaneous papillomatosis caused by Florida manatee (Trichechus manatus
      latirostris [Tm]) papillomavirus 1 (TmPV1) was detected in seven captive manatees
      at the Homosassa Springs Wildlife State Park, Florida, USA, and, subsequently, in
      two wild manatees from the adjacent Homosassa River. Since then, papillomatosis
      has been reported in captive manatees housed in other locations, but not in wild
      animals. To determine TmPV1 antibody prevalence in captive and wild manatees
      sampled at various locations throughout Florida coastal regions, virus-like
      particles, composed of the L1 capsid protein of TmPV1, were generated with a
      baculovirus expression system and used to measure anti-TmPV1 antibodies in an
      enzyme-linked immunosorbent assay. Serologic analysis of 156 manatees revealed a
      TmPV1 antibody prevalence of 26.3%, with no significant difference between
      captive (n=39) and wild (n=117) manatees (28.2% and 25.6%, respectively). No
      antibody-positive wild animal showed PV-induced cutaneous lesions, whereas
      papillomatosis was observed in 72.7% of antibody-positive captive manatees. Our
      data indicate that Florida manatees living in the wild are naturally infected by
      TmPV1 but rarely show TmPV1-induced papillomatosis. Hence, it appears that the
      wild population would not be harmed in a case of contact with captive animals
      without visible lesions and productive infections, which could be thus released
      into the wild.

PMID- 21719833
TI  - Hematologic and blood chemistry reference values for free-ranging muskrats
      (Ondatra zibethicus).
AB  - Baseline hematologic and serum chemistry values are used by veterinarians and
      wildlife biologists to identify abnormally high or low levels of particular blood
      parameters in a target species. This vital information can assist animal care
      providers in making informed decisions on the care of wildlife and help to
      determine diagnoses for certain illnesses. Published blood parameter values are
      not available for wild-caught muskrats (Ondatra zibethicus). We measured 27 blood
      parameter values from 29 free-ranging, riparian muskrats caught from June
      November 2008 in east-central Illinois, USA, and compared mean values between
      adults and juveniles. Adult muskrats had higher levels of globulins
      (F(1,27)=6.394, P <= 0.018) and eosinophils (F(1,25)=6.883, P <= 0.015) than did
      juvenile muskrats, possibly because of increased exposure to parasites and
      allergens over time.

PMID- 21719834
TI  - Outbreak of human herpesvirus type 1 infection in nonhuman primates (Callithrix
      penincillata).
AB  - Human herpesvirus type 1 (HHV-1) is widely dispersed among the human population.
      Although infection is often asymptomatic in humans, nonhuman primates develop a
      severe and often fatal infection. In August 2006, 13 black-tufted marmosets
      (Callithrix penincillata) from a group of 14 presented with clinical apathy,
      anorexia, and ataxia. Physical examination revealed conjunctivitis, erosive or
      ulcerative lesions on the skin, and swollen lymph nodes. Of the 14 animals
      captured, 10 died. Grossly, ulcers and erosions were observed on the skin of
      face, nasal planum, lips, and oral mucosa. Histologically, superficial vesicular
      and erosive stomatitis with associated basophilic intranuclear inclusion bodies
      in the squamous epithelium were observed. Swabs from oral lesions and tissue
      samples from necropsied animals were positive for HHV-1 by nested polymerase
      chain reaction for eight animals.

PMID- 21719835
TI  - Growth of the amphibian pathogen, Batrachochytrium dendrobatidis, in response to
      chemical properties of the aquatic environment.
AB  - Water samples from two of 17 field sites in Arizona (USA) inhibited growth of the
      amphibian pathogen, Batrachochytrium dendrobatidis. Chemical analyses of samples
      revealed statistically significant facilitating or inhibitory activity of certain
      elements. Although low levels of copper were found in environmental samples
      demonstrating facilitated growth, growth was inhibited at concentrations of
      copper sulfate (CuSO(4)) at or greater than 100 ppm.

PMID- 21719836
TI  - Molecular survey of Anaplasma phagocytophilum and Ehrlichia canis in red foxes
      (Vulpes vulpes) from central Italy.
AB  - During the 2007-2008 hunting season, 150 spleen samples were collected from free
      ranging red foxes (Vulpes vulpes) in central Italy. The specimens were tested by
      two nested PCR assays to detect DNA of Anaplasma phagocytophilum, etiologic agent
      of granulocytic ehrlichiosis of animals and humans, and DNA of Ehrlichia canis,
      which causes the monocytic ehrlichiosis in canids. None of the foxes were PCR
      positive for E. canis; 25 (16.6%) were positive for A. phagocytophilum. No
      specific gross alterations were detected at necropsy, and no histopathologic
      lesions found on PCR-positive spleen samples.

PMID- 21719837
TI  - Verocytotoxin-producing Escherichia coli in chamois (Rupicapra rupicapra) and
      cattle in Austria.
AB  - We assessed the prevalence of verotoxigenic Escherichia coli (VTEC) in chamois
      (Rupicapra rupicapra) and livestock grazing on a mountain pasture in Austria
      during June-August 2009. We detected VTEC throughout the sampling period in high
      numbers in cattle as well as in chamois, leading to the assumption that the
      degree of contamination of the environment is high. This is the first report of
      pathogenic E. coli identified in chamois, implicating chamois as a new potential
      reservoir of these zoonotic pathogens. Because the study area also serves
      recreational purposes, there is a risk of humans acquiring infection via direct
      or indirect contact.

PMID- 21719838
TI  - Seroepidemiologic survey for Chlamydia suis in wild boar (Sus scrofa) populations
      in Italy.
AB  - We used serology to estimate the prevalence of exposure to chlamydiae in Italian
      populations of wild boars (Sus scrofa). Sera from 173 hunter-killed wild boars
      harvested during the 2006-2009 hunting seasons in three Italian regions were
      tested for antibodies to Chlamydia suis, Chlamydophila pecorum, Chlamydophila
      abortus, and Chlamydophila psittaci by the microimmunofluorescence test. Antibody
      titers to chlamydiae >= 1:32 were detected in 110 of the 173 samples tested
      (63.6%). Specific reactivity could be assessed only in 44 sera with antibody
      titers to C. suis that were two- to threefold higher than antibody titers against
      the other chlamydial species; the other 66 sera had similar reactivity against
      all the chlamydia species tested. Antibody to C. suis was detected in sera from
      wild boar populations with rare or no known contact with domestic pigs. These
      results suggest that the wild boar could be a chlamydia reservoir and may acquire
      chlamydiae independent of contacts with the domestic pig.

PMID- 21719839
TI  - Survey of haircoat fungal flora for the presence of dermatophytes in a population
      of white-tailed deer (Odocoileus virginianus) in Virginia.
AB  - Before releasing rehabilitated wildlife, patients should be cured of all
      infectious agents that pose a risk to free-roaming wildlife or humans after
      release. Dermatophyte fungi, commonly known as "ringworm," have zoonotic
      potential and may be carried as normal flora on the haircoats of certain species.
      Outbreaks of ringworm are anecdotally reported to occur in white-tailed deer
      (Odocoileus virginianus) fawns, but no prevalence surveys have been conducted on
      the haircoat flora of free-roaming individuals. In November 2008, we tested 60
      legally hunted white-tailed deer for dermatophyte flora by using a modified
      MacKenzie technique. Results indicate it is unlikely that wild, mature white
      tailed deer in Virginia, USA, carry dermato-phyte fungi as normal haircoat flora.
      Therefore, wildlife rehabilitators and hunters are at low risk for dermatophyte
      infection by direct contact with this species. In addition, the RapidVet-D 3 Day
      Test for Veterinary Dermatophytosis was determined to have poor specificity for
      presence of dermatophyte fungi on asymptomatic white-tailed deer in Virginia.

PMID- 21719840
TI  - Detection and characterization of Mycoplasma spp. and Salmonella spp. in free
      living European tortoises (Testudo hermanni, Testudo graeca, and Testudo
      marginata).
AB  - Free-living and captive chelonians might suffer from upper respiratory tract
      disease (URTD), a pathology primarily caused by Mycoplasma agassizii. Wild
      tortoises can also be an important reservoir of Salmonella spp., which are
      commensal in the host reptile but are potential zoonotic agents. Between July
      2009 and June 2010, we screened free-living European tortoises (spur-thighed
      tortoises Testudo graeca, Hermann's tortoises Testudo hermanni, marginated
      tortoises Testudo marginata) temporarily housed in a wildlife center in Italy. We
      molecularly characterized 13 Mycoplasma isolates detected in all Testudo spp.
      studied, and three PCR-positive animals showed typical URTD clinical signs at the
      time of sampling. Three Salmonella enterica serotypes (Abony, Potsdam, Granlo),
      already related to reptile-associated human infections, were also identified.
      These results highlight the potential role played by wildlife recovery centers in
      the spread and transmission of pathogens among wild chelonians and to humans.

PMID- 21719841
TI  - Domestic dog origin of canine distemper virus in free-ranging wolves in Portugal
      as revealed by hemagglutinin gene characterization.
AB  - Serologic evidence for canine distemper virus (CDV) has been described in grey
      wolves but, to our knowledge, virus strains circulating in wolves have not been
      characterized genetically. The emergence of CDV in several non-dog hosts has been
      associated with amino acid substitutions at sites 530 and 549 of the
      hemagglutinin (H) protein. We sequenced the H gene of wild-type canine distemper
      virus obtained from two free-ranging Iberian wolves (Canis lupus signatus) and
      from one domestic dog (Canis familiaris). More differences were found between the
      two wolf sequences than between one of the wolves (wolf 75) and the dog. The
      latter two had a very high nucleotide similarity resulting in identical H gene
      amino acid sequences. Possible explanations include geographic and especially
      temporal proximity of the CDV obtained from wolf 75 and the domestic dog, taken
      in 2007-2008, as opposed to that from wolf 3 taken more distantly in 1998.
      Analysis of the deduced amino acids of the viral hemagglutinin revealed a glycine
      (G) and a tyrosine (Y) at amino acid positions 530 and 549, respectively, of the
      partial signaling lymphocytic activation molecule (SLAM)-receptor binding region
      which is typically found in viral strains obtained from domestic dogs. This
      suggests that the CDV found in these wolves resulted from transmission events
      from local domestic dogs rather than from wildlife species.

PMID- 21719842
TI  - Trichomonad infection in endemic and introduced columbids in the Seychelles.
AB  - Island endemic avifaunas face many threats, including the now well-documented
      impacts of pathogens. The impacts of pathogens on the endemic Seychelles
      avifauna, however, have been little studied. The protozoan parasite Trichomonas
      gallinae has been shown to reduce survival and reproductive success of the
      endemic Pink Pigeon Columba mayeri on the nearby island of Mauritius. I
      investigated trichomonad infection prevalence and pathogenicity in endemic
      Seychelles Blue Pigeons, Alectroenas pulcherrima, and two introduced species of
      columbid, the Madagascar Turtle-dove, Streptopelia picturata, and the Barred
      Ground Dove, Geopelia striata, on the Seychelles island of Mahe during September
      October 2007. I asked whether: 1) trichomonad infections occur in these species;
      2) prevalence varies among species; and 3) birds show any signs of pathogenicity
      consistent with tricho-monosis. I use the results to assess the potential threat
      of this pathogen to A. pulcherrima. All three species were infected with
      trichomonads, and the overall prevalence was 27.5%. Alectroenas pulcherrima had
      higher prevalence (47.1%) than the two introduced species combined (24.3%). No
      infected individuals showed any signs of disease. These findings suggest that
      trichomonad parasites should be considered as a potential disease threat to the
      A. pulcherrima population.

PMID- 21719843
TI  - European hares in Chile: a different lagomorph reservoir for Mycobacterium avium
      subsp. paratuberculosis?
AB  - Ruminants are the principal host for infection by Mycobacterium avium subsp.
      paratuberculosis (Map), the cause of Johne's disease. Based on studies of a Map
      infected population of European rabbits (Oryctolagus cuniculus) in Scotland,
      lagomorphs as a broad taxonomic order were proposed as potential nonruminant
      reservoirs for Map. To determine whether a different lagomorph species may serve
      as a wildlife reservoir, we investigated Map infection in European hares (Lepus
      europaeus) sharing habitat with known Map-infected dairy cattle in southern
      Chile. Fecal, mesenteric lymph node, and ileal samples were aseptically collected
      from 385 wild hares for liquid culture and real-time polymerase chain reaction
      identification of acid-fast isolates. All tissue samples were also acid-fast
      stained and examined microscopically. We isolated Map from at least one tissue
      from 48 hares (12.6%) and fecal samples from 16 hares (4.2%). No Map was found in
      tissues of eight of the fecal-culture-positive hares. Histologically, all tissues
      from all hares were within normal limits, and no acid-fast organisms were
      observed in any sample. Active infection, implying amplification of the organism
      secondary to resultant disease, was not evident. With this report Map isolations
      on a population versus incidental detection have now been made from two lagomorph
      species. However, although the rabbit population studied in Scotland appears to
      function as a Map reservoir, the hares studied in Chile appear to be a dead-end
      host, serving only as potential mechanical vectors for the organism.

PMID- 21719844
TI  - Failure of fallow deer (Dama dama) to develop chronic wasting disease when
      exposed to a contaminated environment and infected mule deer (Odocoileus
      hemionus).
AB  - We monitored a herd of fallow deer (Dama dama) for evidence of prion infection
      for 7 yr by periodic postmortem examination of animals from the herd. The fallow
      deer were exposed to the chronic wasting disease (CWD) agent from mule deer by
      living in a paddock considered contaminated with infectivity from its history of
      housing CWD infected deer and, after the first year of the study, by comingling
      with infected mule deer (Odocoileus hemionus). At least 8 of 12 mule deer serving
      as sentinels for prion transmission and 25 additional mule deer serving as
      sources of infectivity developed clinical CWD or were otherwise confirmed to be
      infected with CWD via lymphoid tissue immunohistochemistry (IHC). In contrast,
      none of the 41 exposed fallow deer showed clinical signs suggestive of CWD, IHC
      staining of disease-associated prion in lymphoid or brain tissues, or evidence of
      spongiform degeneration in sections of brain stem at the level of the obex when
      sampled 18 mo to 7 yr after entering the mule deer paddock. The absence of
      clinical disease and negative IHC results in fallow deer housed in the same
      contaminated paddock for up to 7 yr and almost continuously exposed to CWD
      infected mule deer for up to 6 yr suggests a species barrier or other form of
      resistance preventing fallow deer infection by the CWD agent or delaying
      progression of the disease in this species.

PMID- 21719845
TI  - Prevalence of Trichinella spp. in black bears, grizzly bears, and wolves in the
      Dehcho Region, Northwest Territories, Canada, including the first report of T.
      nativa in a grizzly bear from Canada.
AB  - Samples of muscle from 120 black bears (Ursus americanus), 11 grizzly bears
      (Ursus arctos), and 27 wolves (Canis lupus) collected in the Dehcho Region of the
      Northwest Territories from 2001 to 2010 were examined for the presence of
      Trichinella spp. larvae using a pepsin-HCl digestion assay. Trichinella spp.
      larvae were found in eight of 11 (73%) grizzly bears, 14 of 27 (52%) wolves, and
      seven of 120 (5.8%) black bears. The average age of positive grizzly bears, black
      bears, and wolves was 13.5, 9.9, and approximately 4 yr, respectively. Larvae
      from 11 wolves, six black bears, and seven grizzly bears were genotyped. Six
      wolves were infected with T. nativa and five with Trichinella T6, four black
      bears were infected with T. nativa and two with Trichinella T6, and all seven
      grizzly bears were infected with Trichinella T6 and one of them had a coinfection
      with T. nativa. This is the first report of T. nativa in a grizzly bear from
      Canada. Bears have been linked to trichinellosis outbreaks in humans in Canada,
      and black bears are a subsistence food source for residents of the Dehcho region.
      In order to assess food safety risk it is important to monitor the prevalence of
      Trichinella spp. in both species of bear and their cohabiting mammalian food
      sources.

PMID- 21719846
TI  - Prevalence of Campylobacter in wild birds of the mid-Atlantic region, USA.
AB  - We evaluated the occurrence of three Campylobacter species--C. jejuni, C. coli,
      and C. lari--from 333 wild bird fecal samples collected at Tri-State Bird Rescue
      and Research in Newark, Delaware, in 2008. Using multiplex polymerase chain
      reaction, we detected C. jejuni from six avian families with an overall
      prevalence rate of 7.2%. We did not detect any other Campylobacter species.
      Campylobacter jejuni prevalence ranged widely between different avian families
      with crows (Corvidae) and gulls (Laridae) having the highest prevalence rates
      (23% and 25%, respectively).

PMID- 21719847
TI  - Effective immobilizing doses of medetomidine-ketamine in free-ranging, wild
      Norwegian reindeer (Rangifer tarandus tarandus).
AB  - Combinations of medetomidine and ketamine were evaluated in free-ranging, wild
      Norwegian reindeer (Rangifer tarandus tarandus) as part of a reintroduction
      program in southwestern Norway in November 1995 and November 1996. The drugs were
      administered by dart from a helicopter. The mean (SD) effective immobilizing
      doses for 29 adults (8 males, 21 females) were 0.21 (0.04) mg medetomidine/kg and
      1.0 (0.2) mg ketamine/ kg based on estimated body mass. There was no significant
      difference in mean induction times between males and females. However, animals
      with optimal hits (shoulder or thigh muscles; n=16) had a significantly shorter
      (P<0.05) mean induction time than did animals with suboptimal hits (abdomen or
      flank; n=13), 5.6 (2.2) min and 11.1 (4.7) min, respectively. Inductions were
      calm, and immobilized animals were maintained in sternal recumbency. Clinical
      side effects included hypoxemia and hyperthermia in most animals. For reversal,
      all animals received 5 mg atipamezole per mg medetomidine, half intravenously and
      half intramuscularly, and the mean (SD) time to standing was 3.7 (3.6) min.

PMID- 21719848
TI  - PCR prevalence of Ranavirus in free-ranging eastern box turtles (Terrapene
      carolina carolina) at rehabilitation centers in three southeastern US states.
AB  - Ranaviruses (genus Ranavirus) have been observed in disease epidemics and mass
      mortality events in free-ranging amphibian, turtle, and tortoise populations
      worldwide. Infection is highly fatal in turtles, and the potential impact on
      endangered populations could be devastating. Our objectives were to determine the
      prevalence of ranavirus DNA in blood and oral swabs, report associated clinical
      signs of infection, and determine spatial distribution of infected turtles. Blood
      and oral swabs were taken from 140 eastern box turtles (Terrapene carolina
      carolina) that were presented to the wildlife centers at the University of
      Tennessee (UT; n=39), Wildlife Center of Virginia (WCV; n=34), and North Carolina
      State University (NCSU; n=36), as well as a free-ranging nonrehabilitation
      population near Oak Ridge, Tennessee (OR; n=39) March-November 2007. Samples were
      evaluated for ranavirus infection using polymerase chain reaction (PCR) targeting
      a conserved portion of the major capsid protein. Two turtles, one from UT and one
      from NCSU, had evidence of ranavirus infection; sequences of PCR products were
      100% homologous to Frog Virus 3. Prevalence of ranavirus DNA in blood was 3, 0,
      3, and 0% for UT, WCV, NCSU, and OR, respectively. Prevalence in oral swab
      samples was 3, 0, and 0% for UT, WCV, and NCSU, respectively. Wildlife centers
      may be useful in detection of Ranavirus infection and may serve as a useful early
      monitoring point for regional disease outbreaks.

PMID- 21719849
TI  - Use of rhodamine B as a biomarker for oral plague vaccination of prairie dogs.
AB  - Oral vaccination against Yersinia pestis could provide a feasible approach for
      controlling plague in prairie dogs (Cynomys spp.) for conservation and public
      health purposes. Biomarkers are useful in wildlife vaccination programs to
      demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential
      biomarker for oral plague vaccination because it allows nonlethal sampling of
      animals through hair, blood, and feces. We found that RB is an appropriate marker
      for bait uptake studies of <60 days in black-tailed prairie dogs (C.
      ludovicianus) when used at concentrations <0.5% of bait mass dosed to deliver >10
      mg RB per kg target animal mass. Whiskers with follicles provided the best sample
      for RB detection.

PMID- 21719850
TI  - Clonal lineages, antibiotic resistance and virulence factors in vancomycin
      resistant enterococci isolated from fecal samples of red foxes (Vulpes vulpes).
AB  - Fourteen vanA-containing enterococcal isolates were detected in seven of 52 fecal
      samples (13.5%) from free-ranging red foxes in Portugal. Nine of the vanA
      containing isolates were Enterococcus faecium and five were E. durans. Both
      sequence types, ST262 and ST273, were identified among E. faecium isolates.

PMID- 21719851
TI  - Detection of Clostridium difficile and Salmonella in feral swine population in
      North Carolina.
AB  - We sampled 161 feral pigs in eastern North Carolina, USA, to determine the
      prevalence and antimicrobial resistance profile of Clostridium difficile and
      Salmonella. Seven (4.4%) and eight (5.0%) pigs tested positive for C. difficile
      and Salmonella, respectively, highlighting the importance of determining the
      epidemiology of these pathogens in feral pigs.

PMID- 21719852
TI  - Nilgai antelope in northern Mexico as a possible carrier for cattle fever ticks
      and Babesia bovis and Babesia bigemina.
AB  - Of 20 blood samples from nilgais from Mexico, five were polymerase chain reaction
      positive for Babesia bigemina and one for Babesia bovis. Positive samples had the
      expected 170 (B. bigemina) and 291 (B. bovis) base pairs and were identical to
      Gen-Bank B. bigemina accession S45366 and B. bovis M38218.

PMID- 21719853
TI  - Mycobacterial screening of Czech red deer (Cervus elaphus) populations in
      overwintering sites, 2004-2006.
AB  - One isolate of Mycobacterium avium subsp. paratuberculosis was detected in 2,212
      fecal samples of wild deer assembled in overwintering sites (OwS). Neither M.
      bovis nor M. a. subsp. avium was found. Therefore, congregating deer in OwSs does
      not automatically lead to the amplification of these pathogens among animals in
      OWSs.

PMID- 21719854
TI  - Ingestion of lead and nontoxic shot by Green-winged Teal (Anas crecca) and
      Northern Shovelers (Anas clypeata) from the mid-Gulf Coast of Texas, USA.
AB  - Ninety-eight Green-winged Teal (Anas crecca) and 84 Northern Shoveler (Anas
      clypeata) gizzards were examined for ingested shot. One Northern Shoveler had
      lead and three had steel shot; 24 teal and 17 shovelers had composite nontoxic
      shot or nonlead metal fragments. Prevalence of ingested lead appears minimal and
      consistent with other studies conducted after lead-shot bans.

PMID- 21719855
TI  - Detection of a novel gammaherpesvirus in koalas (Phascolarctos cinereus).
AB  - A novel gammaherpesvirus was detected in wild koalas (Phascolarctos cinereus)
      captured at different locations during 2010. Sequence analysis of the DNA
      polymerase gene revealed that the virus was genetically distinct from all known
      gammaherpesviruses. This is the first herpesvirus to be definitively identified
      in the Vombatiforme suborder (koalas and wombats).

PMID- 21719856
TI  - Isolation of low-pathogenic H7N3 avian influenza from wild birds in Peru.
AB  - Wild birds serve as natural reservoirs and sometimes harbor low-pathogenic avian
      influenza viruses. However, mutation of the virus can result in highly pathogenic
      strains, often more common among H5 and H7 genotypes. We report the isolation of
      a low-pathogenic H7N3 avian influenza in a Peruvian wetland.

PMID- 21719857
TI  - Alternaria fungal dermatitis in a free-ranging javelina (Pecari tajacu).
AB  - We report a javelina from Pinal County, Arizona, USA, with severe fungal
      dermatitis and cellulitis. Extreme emaciation and rostral disfiguration,
      including left-lateral displacement of the nasal planum, justified euthanasia. A
      pus-filled tract within the rostrum was observed. Histopathology revealed
      granulomatous inflammation with hyphae morphologically consistent with Alternaria
      sp. isolated by culture.

PMID- 21719858
TI  - Pasteurellaceae from Colorado bighorn sheep herds.
AB  - We compared phenotypic and genotypic characterizations of 88 Pasteurellaceae
      isolates from bighorn sheep (Ovis canadensis) in the course of exploring
      epizootiologic relationships. Based on our observations, adopting contemporary
      taxonomic conventions and using molecular methods to detect and compare
      Pasteurellaceae may help improve understanding of bighorn respiratory disease
      epizootiology and management.

PMID- 21719860
TI  - Further experience with permafacial implants for lip augmentation: a review of
      100 implants.
AB  - BACKGROUND: Although fillers and surgical lip lifts are effective ways of
      treating the perioral area, both have inherent downsides. Fillers lack
      permanence, and lip lifts do not address the issue of fullness. OBJECTIVES: The
      authors present the results of a long-term follow-up study of Permafacial
      implants (SurgiSil LLC, Plano, Texas) for lip augmentation. This report is a
      follow-up from their first publication. The original publication demonstrated the
      benefit of the procedure at the time of a facelift. The present study reports a
      long-term follow-up on all of the authors' first 50 patients. METHODS: The
      authors' original publication demonstrated the benefits of inserting Permafacial
      implants concurrent with a facelift procedure. In this long-term follow-up study,
      the results of the first 100 implants (50 patients) are presented; this initial
      group of patients was followed up for one to two years. Implant migration, lip
      function, implant position, sensation, and patient satisfaction are reviewed.
      RESULTS: Very few complications were reported; they included migration with
      revision, along with patient-requested size adjustments or removal. No extrusions
      were reported. The degree of patient satisfaction with these implants was high.
      COMPLICATIONS: Although the authors initially experienced a significant migration
      rate, a modification in technique reduced this rate over the long term.
      Permafacial implants are an effective method of increasing fullness in the lip
      area, and they are associated with few complications and high patient
      satisfaction.

PMID- 21719861
TI  - Management of hypertension in the facelift patient: results of a national
      consensus survey.
AB  - INTRODUCTION: In the facelift patient, uncontrolled perioperative hypertension is
      a difficult, acute condition that can lead to significant complications. Although
      the treatment of hypertension in the ambulatory medical setting has been
      standardized, its management in the cosmetic surgery setting has been ambiguous.
      OBJECTIVES: The authors evaluate the results of a survey to assess current
      national trends in perioperative facelift hypertension management. METHODS: A 13
      question survey regarding perioperative hypertension management was sent by
      postal mail to 1776 members of the American Society for Aesthetic Plastic Surgery
      (ASAPS). Respondents were queried about their geographic location, caseload
      volume, facelift method, and hematoma rate. RESULTS: A 35.4% response rate was
      attained (629 respondents). Superficial musculoaponeurotic system (SMAS)
      plication performed under general anesthesia as an outpatient procedure was the
      most common facelift technique. Perioperative blood pressure management was
      consistent among all respondents. Beta-blockers were commonly utilized throughout
      the preoperative period. Administration of alpha agonists was reported more
      frequently by surgeons with higher-volume caseloads and more years in practice.
      Reported hematoma rates did not vary with medication. Medical treatment at an
      intraoperative systolic blood pressure (SBP) threshold below 100 (p < .04) and a
      postoperative SBP of greater than 139 (p < .05) significantly increased reported
      hematoma rates. CONCLUSIONS: The data generated from the survey suggest that the
      timing of treating hypertension deserves more attention than the actual
      medication administered. Proper perioperative care of the facelift patient is
      paramount in the reduction of hematoma rates. Preexisting hypertension correlates
      with a higher hematoma rate, though this study also suggests that normotensive
      anesthesia, as well as strict postoperative blood pressure control did contribute
      to a reduction in hematoma rate.

PMID- 21719862
TI  - Porcine cartilage model for simulation of nasal tip aesthetics and mechanics.
AB  - BACKGROUND: The aesthetics of the human nose is highly dependent on the complex
      structure of the lower lateral cartilages (LLC). Understanding optimum shape and
      mechanical properties of the LLC is pivotal to achieving satisfactory results in
      nasal tip rhinoplasty. OBJECTIVE: The authors introduce an ex vivo animal model
      to replicate the shape and mechanics of human nasal LLC as a tool for research
      and surgical education. METHODS: Seven fresh pig heads were obtained from a local
      butcher shop. Nasal cartilage was harvested in a replicable manner and fashioned
      into appropriate shapes and dimensions based on the authors' human cadaver
      studies. Sutures were placed to approximate the cartilage pairs into appropriate
      human anatomical position. RESULTS: The porcine cartilage model replicated
      analogous structures, including the medial crura and the lateral crura, with
      appropriate cephalic orientation and domal angles. The anterior-posterior
      dimensions of the medial crura, intermediate crura, and lateral crura were 4 mm,
      6 mm, and 10 mm, respectively. Cartilage thickness was approximately 1 mm
      throughout the specimen. Cephalic orientation of the lateral crura was sculpted
      to 45 degrees . The average angle of divergence was 54 degrees  and varied
      according to the physiological shape of the porcine nasal vault (range, 43-74
      degrees ). Average interdomal distance was 13.3 mm (range, 9-18 mm), and average
      domal width was 6.2 mm (range, 5-7 mm). CONCLUSIONS: This novel porcine model
      mimics human LLC and is inexpensive, easy to construct, and highly replicable.
      This model can be used as a valuable educational resource for training novice
      surgeons in the principles of nasal tip rhinoplasty. Additionally, our construct
      has broad applications in studying LLC geometry and mechanics.

PMID- 21719863
TI  - Labioplasty: anatomy, etiology, and a new surgical approach.
AB  - Increasing numbers of women are seeking correction of labial hypertrophy for
      aesthetic and/or functional reasons. It is therefore important for plastic
      surgeons to become familiar with labioplasty surgical techniques. The authors
      review the history and current status of labioplasty surgery for practicing
      plastic surgeons, with particular emphasis on anatomy, diagnosis, indications,
      and various techniques.

PMID- 21719864
TI  - Commentary on: labioplasty: anatomy, etiology, and a new surgical approach.

PMID- 21719865
TI  - Investigator global evaluations of efficacy of injectable poly-L-lactic acid
      versus human collagen in the correction of nasolabial fold wrinkles.
AB  - BACKGROUND: Injectable poly-L-lactic acid (PLLA) is indicated in the United
      States for use in immune-competent patients for correction of shallow-to-deep
      nasolabial fold contour deficiencies and other facial wrinkles in which a deep
      dermal grid pattern injection technique is appropriate. It is also indicated for
      restoration and/or correction of signs of lipoatrophy in patients with human
      immunodeficiency virus. OBJECTIVE: The authors examine the efficacy of injectable
      PLLA for correction of nasolabial fold wrinkles, based on Investigator Global
      Evaluations (IGE). METHODS: A randomized, multicenter, subject-blinded, parallel
      group study compared injectable PLLA versus human collagen for correction of
      nasolabial fold wrinkles for 13 months after up to four treatments (intent-to
      treat population, 233). Injectable PLLA-treated subjects were followed up for an
      additional 12 months (total, 25 months) after the final treatment session.
      Efficacy was also assessed through secondary IGE for improvement, which is the
      subject of this report. RESULTS: IGE reports of improvement were significantly
      greater in subjects who received injectable PLLA versus those who received human
      collagen (p < .001). Overall improvement with injectable PLLA was 100% three
      weeks after the final treatment, remaining above 85% through month 25. Overall
      IGE of improvement with human collagen declined from 94.0% at week three to 6.0%
      at month 13. Both treatment groups had similar safety profiles. CONCLUSIONS: IGE
      of improvement were significantly greater with injectable PLLA treatment than
      with human collagen treatment at all time points following the last treatment.
      Injectable PLLA treatment continued to show a beneficial effect for up to 25
      months.

PMID- 21719866
TI  - Further enhancement of facial appearance with a hydroquinone skin care system
      plus tretinoin in patients previously treated with botulinum toxin Type A.
AB  - BACKGROUND: A hydroquinone (HQ) skin care system has been designed for use in
      conjunction with nonsurgical procedures. OBJECTIVE: The authors evaluate the
      efficacy of this system plus tretinoin for improving facial appearance in
      comparison to a standard skin care regimen in users of botulinum toxin Type A
      (BoNT-A). METHODS: In this multicenter, randomized, investigator-masked, parallel
      group study, 61 patients who received upper facial treatment with BoNT-A at a
      plastic surgery or dermatology clinic were randomly assigned to apply either the
      HQ system (cleanser, toner, proprietary 4% hydroquinone, exfoliant, and
      sunscreen) plus 0.05% tretinoin cream or a standard skin care regimen (cleanser,
      moisturizer, and sunscreen) for 120 days. Outcomes were assessed by the
      investigators and through a patient questionnaire. RESULTS: Compared with
      standard skin care, the HQ system plus tretinoin resulted in significantly milder
      fine lines/wrinkles and hyperpigmentation at Days 30, 90, and 120 (p <= .05) and
      significantly superior overall ratings for each of nine patient assessments at
      Days 90 and 120 (p <= .05). A relatively greater proportion of patients using the
      HQ system plus tretinoin believed that their study treatment had further enhanced
      the improvements attained with BoNT-A (86% vs 8%). Both regimens were generally
      well tolerated. CONCLUSIONS: Adjunctive use of the HQ system plus tretinoin can
      further enhance the improvements in facial appearance attained with BoNT-A.
      Applying the HQ system plus tretinoin offers multiple clinical benefits over
      standard skin care, including significantly greater improvements in fine
      lines/wrinkles and hyperpigmentation.

PMID- 21719867
TI  - Animal model of implant capsular contracture: effects of chitosan.
AB  - BACKGROUND: The mechanism(s) responsible for breast capsular contracture (CC)
      remain unknown, but inflammatory pathways play a role. Various molecules have
      been attached to implant shells in the hope of modifying or preventing CC. The
      intrinsic antibacterial and antifungal activities of chitosan and related
      oligochitosan molecules lend themselves well to the study of the infectious
      hypothesis; chitosan's ability to bind to growth factors, its hemostatic action,
      and its ability to activate macrophages, cause cytokine stimulation, and increase
      the production of transforming growth factor (TGF)-beta1 allow study of the
      hypertrophic scar hypothesis. OBJECTIVE: The authors perform a comprehensive
      evaluation, in a rabbit model, of the relationship between CC and histological,
      microbiological, and immunological characteristics in the presence of a
      chitooligosaccharide (COS) mixture and a low molecular weight chitosan (LMWC).
      METHODS: Eleven adult New Zealand rabbits were each implanted with three silicone
      implants: a control implant, one impregnated with COS, and one impregnated with
      LMWC. At four-week sacrifice, microdialysates were obtained in the capsule
      implant interfaces for tumor necrosis factor alpha (TNF-alpha) and interleukin-8
      (IL-8) level assessment. Histological and microbiological analyses were
      performed. RESULTS: Baker grade III/IV contractures were observed in the LMWC
      group, with thick capsules, dense connective tissue, and decreased IL-8 levels (p
      < .05) compared to control and COS groups. Capsule tissue bacterial types and
      microdialysate TNF-alpha levels were similar among all groups. CONCLUSIONS:
      Chitosan-associated silicone implantation in a rabbit model resulted in Baker
      grade III/IV CC. This preclinical study may provide a model to test various
      mechanistic hypotheses of breast capsule formation and subsequent CC.

PMID- 21719868
TI  - Definitive diagnosis and management of axillary hyperhidrosis: the VapoMeter and
      suction-assisted arthroscopic shaving.
AB  - BACKGROUND: Axillary hyperhidrosis is a benign, yet significant, disability that
      not only impairs social interaction but also affects occupational activities.
      OBJECTIVES: The author provides a detailed description of axillary shaving, a
      procedure with proven results. He also describes the use of the VapoMeter (Delfin
      Technologies, Stamford, Connecticut), which accurately and easily measures
      sweating in g/m(2)/h. METHODS: Although a total of 45 patients have received this
      surgery since 2005, this report includes only the last eight patients (16 axilla)
      for whom both pre- and postoperative VapoMeter readings are available. RESULTS:
      The average preoperative VapoMeter reading was 473 g/m(2)/h (range, 98-998),
      which improved to an average of 58 g/m(2)/h postoperatively (range, 21-227). As a
      comparison, controls for all axilla had an average measurement of 23.7 g/m(2)/h
      (range, 18-31). CONCLUSIONS: When combined with the effective surgical technique
      of axillary shaving, the VapoMeter provides an objective measure to both
      definitively diagnose and confirm results of the shaving. With this protocol,
      patients who require surgical intervention for their hyperhidrosis can be
      reassured that the procedure is indeed effective in improving their condition.

PMID- 21719869
TI  - Online marketing strategies of plastic surgeons and clinics: a comparative study
      of the United Kingdom and the United States.
AB  - The cosmetic surgery market is a rapidly growing sector of healthcare, and the
      use of marketing strategies is now an integral part of any cosmetic surgery
      practice. In this study, the authors review 50 Web sites from practitioners in
      London and New York to quantify the utilization of online marketing, comparing
      results between the United Kingdom and the United States.

PMID- 21719870
TI  - Abdominoplasty with thorough concurrent circumferential abdominal tumescent
      liposuction.
AB  - Abdominoplasty, the removal of excess skin combined with muscle plication of a
      patient's abdominal region, can yield pleasing postoperative results alone, but
      adding significant concurrent circumferential abdominal liposuction to the
      procedure can dramatically improve the overall shape and contour of the final
      result. The perceived risk of performing this combined procedure involves
      potential skin necrosis resulting from devascularization of the abdominal flap,
      but when performed with proper technique-including thorough tumescent
      infiltration and vascular preservation during the liposuction portion-the
      procedure delivers superior results with a minimal risk of ischemia and necrosis.

PMID- 21719871
TI  - Disclosing conflicts of interest to maintain ethical integrity.

PMID- 21719872
TI  - Transforming mental health services.
AB  - Specialist teams have had a major impact on service delivery in England. Their
      effectiveness is now being questioned and integrated teams are developing in some
      areas. However, the gains made in terms of improved access, engagement and early
      intervention must not be lost.

PMID- 21719873
TI  - Detection of bipolar disorder.
AB  - Major depressive episodes are common in bipolar disorder, which consequently may
      be misdiagnosed as major depressive disorder. Improved detection of bipolar
      disorder rests upon better ascertainment of a history of hypomania.
      Antidepressants are of dubious benefit in bipolar disorder and more accurate
      diagnosis of depression would promote better treatment.

PMID- 21719874
TI  - The case for early intervention in anorexia nervosa: theoretical exploration of
      maintaining factors.
AB  - Here we revisit and reinterpret the original study in which the so-called
      'Maudsley (London) model' of family therapy was compared with individual therapy
      for anorexia nervosa. Family therapy was more effective in adolescents with a
      short duration of illness. However, this is only part of the story. A later study
      describing the 5-year outcome contains important information. Those adolescents
      randomised to family therapy achieved a better outcome 5 years later. Moreover,
      the group with an onset in adolescence but who had been ill for over 3 years had
      a poor response to both family and individual therapy, suggesting that unless
      effective treatment is given within the first 3 years of illness onset, the
      outcome is poor. We examine other evidence supporting this conclusion and
      consider the developmental and neurobiological factors that can account for this.

PMID- 21719875
TI  - Cross-cultural attitudes to help-seeking among individuals who are suicidal: new
      perspective for policy-makers.
AB  - World Mental Health Survey data demonstrate that a high proportion of people who
      are suicidal receive no treatment and that, contrary to previous assumptions,
      attitudes to treatment constitute greater barriers to help-seeking than do stigma
      or structural/financial constraints. We explore how suicide-prevention policy
      makers might respond to Bruffaerts et al's findings.

PMID- 21719876
TI  - The four dimensions: a model for the social aetiology of psychosis.
AB  - Recently, there has been increasing focus on prevention of mental illness, early
      intervention and the promotion of mental health. The social determinants of
      health and public health approaches are considered key. Early intervention has
      focused on psychotic disorders but prevention has not. This may in part reflect
      the fact that public health planners do not have a clear model for how social
      determinants influence the risk of developing a psychotic illness. Drawing on
      biological, genetic and epidemiologic evidence regarding the relationship between
      social risk factors and psychosis, this paper outlines a conceptual framework for
      understanding how individual and ecological factors contribute and interact to
      modulate the risk of developing psychotic illness. The framework asserts that
      there are four dimensions: individual factors; ecological factors; the
      interaction between individual and ecological factors; and time. It may help
      those considering interventions to understand the multilevel and multifactorial
      effects of social factors on the aetiology of psychotic illness, to develop
      targeted strategies for the prevention of psychotic illness and serve as a
      template for the assessment of initiatives.

PMID- 21719877
TI  - Long-term psychodynamic psychotherapy in complex mental disorders: update of a
      meta-analysis.
AB  - BACKGROUND: Dose-effect relationship data suggest that short-term psychotherapy
      is insufficient for many patients with chronic distress or personality disorders
      (complex mental disorders). AIMS: To examine the comparative efficacy of long
      term psychodynamic psychotherapy (LTPP) in complex mental disorders. METHOD: We
      conducted a meta-analysis of controlled trials of LTPP fulfilling the following
      inclusion criteria: therapy lasting for at least a year or 50 sessions; active
      comparison conditions; prospective design; reliable and valid outcome measures;
      treatments terminated. Ten studies with 971 patients were included. RESULTS:
      Between-group effect sizes in favour of LTPP compared with less intensive (lower
      dose) forms of psychotherapy ranged between 0.44 and 0.68. CONCLUSIONS: Results
      suggest that LTPP is superior to less intensive forms of psychotherapy in complex
      mental disorders. Further research on long-term psychotherapy is needed, not only
      for psychodynamic psychotherapy, but also for other therapies.

PMID- 21719878
TI  - Mental well-being and mental illness: findings from the Adult Psychiatric
      Morbidity Survey for England 2007.
AB  - BACKGROUND: Mental well-being underpins many aspects of health and social
      functioning, and is economically important. AIMS: To describe mental well-being
      in a general population sample and to determine the extent to which mental well
      being and mental illness are independent of one another. METHOD: Secondary
      analysis of a survey of 7293 adults in England. Nine survey questions were
      identified as possible indicators of mental well-being. Common mental disorders
      (ICD-10) were ascertained using the Revised Clinical Interview Schedule (CIS-R).
      Principal components analysis was used to describe the factor structure of mental
      well-being and to generate mental well-being indicators. RESULTS: A two-factor
      solution found eight out of nine items with strong loadings on well-being. Eight
      items corresponding to hedonic and eudaemonic well-being accounted for 36.9% and
      14.3% of total variance respectively. Separate hedonic and eudaemonic well-being
      scales were created. Hedonic well-being (full of life; having lots of energy)
      declined with age, while eudaemonic well-being (getting on well with family and
      friends; sense of belonging) rose steadily with age. Hedonic well-being was lower
      and eudaemonic well-being higher in women. Associations of well-being with age,
      gender, income and self-rated health were little altered by adjustment for
      symptoms of mental illness. CONCLUSIONS: In a large nationally representative
      population sample, two types of well-being were distinguished and reliably
      assessed: hedonic and eudaemonic. Associations with mental well-being were
      relatively independent of symptoms of mental illness. Mental well-being can
      remain even in the presence of mental suffering.

PMID- 21719879
TI  - Childhood abuse, the BDNF-Val66Met polymorphism and adult psychotic-like
      experiences.
AB  - BACKGROUND: The well-established relationship between childhood adversity and
      psychosis is likely to involve other factors such as genetic variants that can
      help us to understand why not everyone exposed to adverse events develops
      psychotic symptoms later in life. AIMS: We investigated the influence of
      childhood abuse and neglect on positive and negative psychotic-like experiences
      in adulthood and the potential moderating effect of the BDNF-Val66Met
      polymorphism. METHOD: Psychotic-like experiences and childhood adversity were
      assessed in 533 individuals from the general population. RESULTS: Childhood abuse
      showed a strong independent effect on the positive dimension of psychotic-like
      experiences (beta = 0.16, s.e. = 0.05, P = 0.002). Furthermore, this association
      was moderated by the BDNF-Val66Met polymorphism (beta = 0.27, s.e. = 0.10, P =
      0.004). CONCLUSIONS: Individuals exposed to childhood abuse are more likely to
      report positive psychotic-like experiences. Met carriers reported more positive
      psychotic-like experiences when exposed to childhood abuse than did individuals
      carrying the Val/Val genotype. Therefore, the observed gene-environment
      interaction effect may be partially responsible for individual variation in
      response to childhood abuse.

PMID- 21719880
TI  - Possible source of bias.

PMID- 21719881
TI  - Predicting the future is a thankless task.

PMID- 21719882
TI  - Key concepts and critical issues on epoetin and filgrastim biosimilars. A
      position paper from the Italian Society of Hematology, Italian Society of
      Experimental Hematology, and Italian Group for Bone Marrow Transplantation.

PMID- 21719883
TI  - Concerns about the use of biosimilar granulocyte colony-stimulating factors for
      the mobilization of stem cells in normal donors: position of the World Marrow
      Donor Association.

PMID- 21719884
TI  - Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic
      syndrome and acute myeloid leukemia with chromosome 5 abnormalities.
AB  - BACKGROUND: Patients with chromosome 5 abnormalities and high-risk
      myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We
      hypothesized that increasing doses of lenalidomide may benefit this group of
      patients by inhibiting the tumor clone, as assessed by fluorescence in situ
      hybridization for del(5q31). DESIGN AND METHODS: Twenty-eight patients at
      diagnosis or with relapsed disease and not eligible for standard therapy (16 with
      acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic
      syndrome) were enrolled in this prospective phase II multicenter trial and
      treated with lenalidomide up to 30 mg daily for 16 weeks. Three patients had
      isolated del(5q), six had del(5q) plus one additional aberration, 14 had del(5q)
      and a complex karyotype, four had monosomy 5, and one had del(5q) identified by
      fluorescence in situ hybridization only. RESULTS: Major and minor cytogenetic
      responses, assessed by fluorescence in situ hybridization, were achieved in 5/26
      (19%) and 2/26 (8%) patients, respectively, who received one or more dose of
      lenalidomide, while two patients achieved only a bone marrow response. Nine of
      all 26 patients (35%) and nine of the ten who completed the 16 weeks of trial
      responded to treatment. Using the International Working Group criteria for acute
      myeloid leukemia and myelodysplastic syndrome the overall response rate in
      treated patients with acute myeloid leukemia was 20% (3/15), while that for
      patients with myelodysplastic syndrome was 36% (4/11). Seven patients stopped
      therapy due to progressive disease and nine because of complications, most of
      which were disease-related. Response rates were similar in patients with isolated
      del(5q) and in those with additional aberrations. Interestingly, patients with
      TP53 mutations responded less well than those without mutations (2/13 versus 5/9,
      respectively; P=0.047). No responses were observed among 11 cases with
      deleterious TP53 mutations. CONCLUSIONS: Our data support a role for higher doses
      of lenalidomide in poor prognosis patients with myelodysplastic syndrome and
      acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier
      NCT00761449).

PMID- 21719885
TI  - Plasmacytoma-like post-transplant lymphoproliferative disorder, a rare subtype of
      monomorphic B-cell post-transplant lymphoproliferation, is associated with a
      favorable outcome in localized as well as in advanced disease: a prospective
      analysis of 8 cases.
AB  - Post-transplantation lymphoproliferative disorder (PTLD) with plasmacellular
      differentiation has been reported as a rare subtype of monomorphic B-cell post
      transplant lympho-proliferation with histological and immunophenotypical features
      of plasmacytoma in the non-transplant population. Here we present clinical,
      laboratory and histopathological features, treatment and outcome of 8 patients
      from the German prospective PTLD registry. Clinically, extranodal manifestations
      were common while osteolytic lesions were rare and none of the patients had bone
      marrow involvement. Immunohistochemistry showed light chain restriction and
      expression of CD138 without CD20 expression in all samples. An association with
      Epstein-Barr virus was found in 3 out of 8 cases. We suggest that the Ann Arbor
      classification is most useful for this disease entity and report a generally good
      response to treatment including reduction of immuno-suppression, surgery and
      irradiation in localized disease and systemic chemotherapy analogous to
      plasmacell myeloma in advanced disease.

PMID- 21719886
TI  - Cystic fibrosis in children and adults.

PMID- 21719887
TI  - Highlights of the 2010 North American Cystic Fibrosis Conference.

PMID- 21719888
TI  - Why bother to take vitamins?

PMID- 21719889
TI  - Mechanisms and applications of hypertonic saline.

PMID- 21719890
TI  - Parents as equal partners in the paediatric cystic fibrosis multidisciplinary
      team.

PMID- 21719891
TI  - Gout and hyperuricaemia in adults with cystic fibrosis.
AB  - Gout has not been described previously as a complication in cystic fibrosis (CF).
      Here we present data on nine CF patients who have presented with symptoms of
      acute gout. This gives an estimated prevalence of gout of around 2.5% in our
      adult CF population, compared to a previously described prevalence in the non-CF
      population of just over 1%. Serum urate is measured routinely at the annual
      review in our unit. Mean (SD) serum urate was 0.40 (0.09) mmol/L in male CF
      patients (n = 108) and 0.31 (0.08) mmol/L in female patients (n = 74). This was
      significantly greater than in historical controls. Thirty-seven percent of male
      CF patients and 36% of female patients had serum urate levels above the upper
      limit of normal.

PMID- 21719892
TI  - Azathioprine in the management of enteropathy in cystic fibrosis.

PMID- 21719893
TI  - Gastroesophageal reflux causing nutritional failure and vomiting in a teenager
      with cystic fibrosis and respiratory failure.

PMID- 21719894
TI  - Treatment massive haemoptysis in cystic fibrosis with tranexamic acid.

PMID- 21719895
TI  - Exercise testing in cystic fibrosis: why (and how)?

PMID- 21719896
TI  - Menthol preference among smokers: association with TRPA1 variants.
AB  - INTRODUCTION: Preference for smoking menthol cigarettes differs from individual
      to individual and population to population in ways that may provide higher levels
      of nicotine intake and contribute to smoking's morbidity and mortality. Menthol
      acts at sites that include the transient receptor potential (TRP) A1 channel that
      is expressed by nociceptors in the lung and airways, suggesting that individual
      and population differences in TRPA1 sequences might contribute to observed
      differences in menthol preference among smokers. METHODS: We have thus sought
      association between menthol preference and common variants in the TRPA1 gene in
      heavier and lighter European-American smokers. Smokers were recruited for studies
      of smoking cessation in North Carolina and of substance abuse genetics in
      Maryland. RESULTS: A common TRPA1 haplotype is defined by 1 missense and 10
      intronic single nucleotide polymorphisms that display significant (.006 < p <
      .05; chi(2)) association with preference for mentholated cigarettes in heavy
      smokers (odds ratio ca. 1.3). There are smaller trends in the same direction in
      lighter smokers. CONCLUSIONS: This TRPA1 haplotype provides a novel biological
      basis for individual differences in menthol preference and possibly for actions
      of other agents that act at TRPA1.

PMID- 21719897
TI  - Musculoskeletal tuberculosis: are you ready to diagnose it?

PMID- 21719898
TI  - Effects of a dairy supplement and resistance training on lean mass and insulin
      like growth factor in women.
AB  - PURPOSE: To examine the effect of yogurt supplementation pre- and postexercise on
      changes in body composition in overweight women engaged in a resistance-training
      program. METHODS: Participants (age = 36.8 +/- 4.8 yr) with a body-mass index of
      29.1 +/- 2.1 kg/m2 were randomized to yogurt supplement (YOG; n = 15) or
      isoenergetic sucrose beverage (CONT; n = 14) consumed before and after exercise
      for 16 wk. Participants were also instructed to reduce energy intake daily (
      1,046 kJ) during the study. Body composition was assessed by dual-energy X-ray
      absorptiometry, waist circumference, and sagittal diameter. Strength was measured
      with 1-repetition maximum. Dietary recalls were obtained by a multipass approach
      using Nutrition Data System software. Insulin-like growth factor-1 and insulin
      like growth-factor-binding protein-3 were measured with ELISA. RESULTS:
      Significant weight losses of 2.6 +/- 4.5 kg (YOG) and 1.2 +/- 2.5 kg (CONT) were
      observed. Total lean weight increased significantly over time in both YOG (0.8 +/
      1.2 kg) and CONT (1.1 +/- 0.9 kg). Significant reductions in total fat (YOG =
      3.4 +/- 4.1 kg vs. CONT = 2.3 +/- 2.4 kg) were observed over time. Waist
      circumference, sagittal diameter, and trunk fat decreased significantly over time
      without group differences. Both groups significantly decreased energy intake
      while maintaining protein intake. Strength significantly increased over time in
      both groups. No changes over time or between groups were observed in hormone
      levels. CONCLUSIONS: These data suggest that yogurt supplementation offered no
      added benefit for increasing lean mass when combined with resistance training and
      modest energy restriction.

PMID- 21719899
TI  - Effect of sodium bicarbonate on [HCO3-], pH, and gastrointestinal symptoms.
AB  - CONTEXT: Sodium bicarbonate (NaHCO3) is often ingested at a dose of 0.3 g/kg body
      mass (BM), but ingestion protocols are inconsistent in terms of using solution or
      capsules, ingestion period, combining NaHCO3 with sodium citrate (Na3C6H5O7), and
      coingested food and fluid. PURPOSE: To quantify the effect of ingesting 0.3 g/kg
      NaHCO3 on blood pH, [HCO3-], and gastrointestinal (GI) symptoms over the
      subsequent 3 hr using a range of ingestion protocols and, thus, to determine an
      optimal protocol. METHODS: In a crossover design, 13 physically active subjects
      undertook 8 NaHCO3 experimental ingestion protocols and 1 placebo protocol.
      Capillary blood was taken every 30 min and analyzed for pH and [HCO3-]. GI
      symptoms were quantified every 30 min via questionnaire. Statistics used were
      pairwise comparisons between protocols; differences were interpreted in relation
      to smallest worthwhile changes for each variable. A likelihood of >75% was a
      substantial change. RESULTS: [HCO3-] and pH were substantially greater than in
      placebo for all other ingestion protocols at almost all time points. When NaHCO3
      was coingested with food, the greatest [HCO3-] (30.9 mmol/kg) and pH (7.49) and
      lowest incidence of GI symptoms were observed. The greatest incidence of GI side
      effects was observed 90 min after ingestion of 0.3 g/kg NaHCO3 solution.
      CONCLUSIONS: The changes in pH and [HCO3-] for the 8 NaHCO3-ingestion protocols
      were similar, so an optimal protocol cannot be recommended. However, the results
      suggest that NaHCO3 coingested with a high-carbohydrate meal should be taken 120
      150 min before exercise to induce substantial blood alkalosis and reduce GI
      symptoms.

PMID- 21719900
TI  - Dietary thiamin and riboflavin intake and blood thiamin and riboflavin
      concentrations in college swimmers undergoing intensive training.
AB  - The purpose of this study was to examine the effect of high-intensity physical
      activity during training on the biochemical status of thiamin and riboflavin in
      athletes. Thiamin and riboflavin concentrations in whole blood of a group of 19
      athletes (6 men and 13 women) were measured during a low-intensity preparatory
      period and compared with measurements taken during a high-intensity training
      period. Additional variables measured included anthropometric characteristics,
      estimated energy expenditure during swim training, distance covered, resting
      energy expenditure obtained by indirect calorimetry, estimated energy requirement
      per day, and dietary intake of energy, thiamin, and riboflavin estimated from 3
      day food records. For both male and female subjects, no major changes were
      observed in anthropometric characteristics or dietary intake, but energy
      expenditure during swim training per day significantly increased in the intensive
      training period (496 +/- 0 kcal in the preparation period compared with 995 +/-
      96 kcal in the intensive-training period for male subjects [p < .001] and 361 +/-
      27 kcal vs. 819 +/- 48 kcal, respectively, for female subjects [p < .001]). Blood
      thiamin concentration decreased significantly during the intensive-training
      period compared with the preparation period (41 +/- 6 ng/ml decreased to 36 +/- 3
      ng/ml for male subjects [p = .048], and 38 +/- 10 ng/ml decreased to 31 +/- 5
      ng/ml for female subjects [p = .004]); however, the concentration of riboflavin
      was unchanged. These results suggest that intense training affects thiamin
      concentration, but not riboflavin concentration, in the whole blood of college
      swimmers.

PMID- 21719901
TI  - Effects of immediate postexercise carbohydrate ingestion with and without protein
      on neutrophil degranulation.
AB  - The purpose of the study was to determine the effects of carbohydrate (CHO)
      intake, with and without protein (PRO), immediately after prolonged strenuous
      exercise on circulating bacterially stimulated neutrophil degranulation. Twelve
      male runners completed 3 feeding interventions, 1 week apart, in randomized order
      after 2 hr of running at 75% VO2max. The feeding interventions included a placebo
      solution, a CHO solution equal to 1.2 g CHO/kg body mass (BM), and a CHO-PRO
      solution equal to 1.2 g CHO/kg BM and 0.4 g PRO/kg BM (CHO+PRO) immediately
      postexercise. All solutions were flavor and water-volume equivalent (12 ml/kg
      BM). Circulating leukocyte counts, bacterially stimulated neutrophil
      degranulation, plasma insulin, and cortisol were determined from blood samples
      collected preexercise, immediately postexercise, and every 30 min until 180 min
      postexercise. The immediate postexercise circulating leukocytosis, neutrophilia,
      and lymphocytosis (p < .01 vs. preexercise) and the delayed lymphopenia (90 min
      postexercise, p < .05 vs. preexercise) were similar on all trials. Bacterially
      stimulated neutrophil degranulation decreased during recovery in control (23% at
      180 min, p < .01 vs. preexercise) but remained above preexercise levels with CHO
      and CHO+PRO. In conclusion, CHO ingestion, with or without PRO, immediately after
      prolonged strenuous exercise prevented the decrease in bacterially stimulated
      neutrophil degranulation during recovery.

PMID- 21719902
TI  - Impact of fluid restriction and ad libitum water intake or an 8% carbohydrate
      electrolyte beverage on skill performance of elite adolescent basketball players.
AB  - Twelve adolescent athletes underwent, in a crossover-design study, 3 separate 90
      min training sessions in the following conditions: no fluid ingestion allowed
      (NF), ad libitum ingestion of water (W), and ad libitum ingestion of a commercial
      8% carbohydrate-electrolyte sports beverage (CSB). After each session athletes
      performed a set of basketball drills (2-point, 3-point, and free-throw shootout,
      suicide sprints, and defensive zigzags). Body weight (before and after sessions),
      rating of perceived exertion (RPE), urine color, and beverage acceptability were
      determined in each session. Athletes also completed a survey about their
      knowledge and behaviors regarding hydration and fluid replacement. The percentage
      of weight loss was significantly higher in NF (2.46% +/- 0.87%) than in the other
      2 conditions (W, 1.08% +/- 0.67%, p = .006; CSB, 0.65% +/- 0.62%, p = .001) but
      also higher in W than CSB (p = .012). RPE was higher in NF (16.8 +/- 1.96) than
      in the W (14.2 +/- 1.99, p = .004) and CSB (13.3 +/- 2.06, p = .002) trials.
      Athletes' fluid intake was positively correlated with proper self-reported
      behaviors (r = .75, p = .005) and knowledge (r = .76, p = .004) about fluid and
      hydration. In conclusion, fluid restriction during exercise was associated with a
      greater level of dehydration and increased perceived exertion but had no impact
      on basketball performance compared with ad libitum drinking of water or a CSB.
      Athletes with more knowledge about hydration and better self-reported hydration
      behaviors ingested more fluids during training sessions.

PMID- 21719903
TI  - Effects of exercise, diet, and their combination on metabolic-syndrome-related
      parameters in OLETF rats.
AB  - This study was conducted to assess the effects of exercise, diet, and their
      combination on metabolic syndrome (MS) risk factors including visceral fat mass
      (VFM), glucose intolerance, and dyslipidemia in OLETF rats. Thirty-two male rats
      were assigned to exercise (OLETF-Ex), dietary treatment (-DT), combination (
      Ex&DT), or sedentary (-Sed) groups. Daily voluntary exercise using a rotary wheel
      was performed in OLETF-Ex. Each treatment was conducted from 21 to 31 wk of age.
      An oral glucose tolerance test was performed before and after the treatment
      period. Absolute levels of VFM, subcutaneous fat mass (SFM), and serum lipids
      including triglyceride, total cholesterol, and LDL-cholesterol (LDL-C) were
      measured after the treatment period. All therapeutic treatments resulted in
      significantly lower levels of body weight, VFM, SFM, and serum lipids than in
      sedentary control rats. All therapeutic treatments were also found to improve
      indices of oral glucose tolerance. Of the 3 therapeutic treatments, serum LDL-C
      levels were significantly lower in OLETF-Ex and OLETF-Ex&DT than in OLETF-Sed.
      The data demonstrate that all therapeutic approaches tested were effective in
      improving a number of MS-related parameters in OLETF rats. However, exercise
      based therapeutic intervention may provide additional benefits for improving fat
      metabolism in MS patients.

PMID- 21719904
TI  - Exercise-induced trace mineral element concentration in regional versus whole
      body wash-down sweat.
AB  - Simultaneous whole-body wash-down (WBW) and regional skin surface sweat
      collections were completed to compare regional patch and WBW sweat calcium (Ca),
      magnesium (Mg), copper (Cu), manganese (Mn), iron (Fe), and zinc (Zn)
      concentrations. Athletes (4 men, 4 women) cycled in a plastic open-air chamber
      for 90 min in the heat. Before exercise, the subjects and cycle ergometer
      (covered in plastic) were washed with deionized water. After the onset of
      sweating, sterile patches were attached to the forearm, back, chest, forehead,
      and thigh and removed on saturation. After exercise, the subjects and cycle
      ergometer were washed with 5 L of 15-mM ammonium sulfate solution to collect all
      sweat minerals and determine the volume of unevaporated sweat. Control trials
      were performed to measure mineral contamination in regional and WBW methods.
      Because background contamination in the collection system was high for WBW Mn,
      Fe, and Zn, method comparisons were not made for these minerals. After correction
      for minimal background contamination, WBW sweat [Ca], [Mg], and [Cu] were 44.6 +/
      20.0, 9.8 +/- 4.8, and 0.125 +/- 0.069 mg/L, respectively, and 5-site regional
      (weighted for local sweat rate and body surface area) sweat [Ca], [Mg], and [Cu]
      were 59.0 +/- 15.9, 14.5 +/- 4.8, and 0.166 +/- 0.031 mg/L, respectively. Five
      site regional [Ca], [Mg], and [Cu] overestimated WBW by 32%, 48%, and 33%,
      respectively. No individual regional patch site or 5-site regional was
      significantly correlated with WBW sweat [Ca] (r = -.21, p = .65), [Mg] (r = .49,
      p = .33), or [Cu] (r = .17, p = .74). In conclusion, regional sweat [Ca], [Mg],
      and [Cu] are not accurate surrogates for or significantly correlated with WBW
      sweat composition.

PMID- 21719905
TI  - Body-density measurement in children: the BOD POD versus Hydrodensitometry.
AB  - OBJECTIVE: To compare estimates of body density (Db) from air-displacement
      plethysmography (ADP) with measured and predicted thoracic-gas-volume (TGV)
      measurements and those from hydrodensitometry (HD) in children. METHODS:
      Seventeen participants (13 male and 4 female; 10.1 +/- 2.20 yr, 42.0 +/- 15.03
      kg, 145.6 +/- 17.41 cm, 30.0 +/- 8.66 kg/m2) were tested using ADP and HD, with
      ADP always preceding HD. Db estimates were compared between ADP with measured
      TGV, ADP with predicted TGV, and the reference measure, HD. Regression analyses
      were used to assess the accuracy of the ADP methods, and potential bias between
      the ADP procedures and HD were evaluated using Bland-Altman analyses. The cross
      validation criteria described by Lohman for estimating Db relative to HD were
      used to interpret the results of the study. RESULTS: A significant difference was
      found between Db estimates from ADP with measured TGV (1.0453 +/- 0.01934 g/cm3)
      and ADP with predicted TGV (1.0415 +/- 0.01858 g/cm3); however, neither was
      significantly different from Db obtained by the reference HD procedure (1.0417 +/
      0.02391 g/cm3). For both ADP procedures, regression analyses produced an r =
      .737-.738, r2 = .543-.544, and SEE = 0.02 g/cm3, and the regression lines
      deviated significantly from the line of identity; however, no significant biases
      were indicated. CONCLUSIONS: Despite no significant mean differences between Db
      estimates from the ADP procedures and HD, more cross-validation research is
      needed before recommending the BOD POD for routine use with children in clinical
      and research settings.

PMID- 21719906
TI  - Nutrition knowledge in athletes: a systematic review.
AB  - CONTEXT: Nutrition education aims to enhance knowledge and improve dietary intake
      in athletes. Understanding athletes' nutrition knowledge and its influence on
      dietary intake will inform nutrition-education programs in this population.
      PURPOSE: To systematically review the level of nutrition knowledge in athletes,
      benchmark this against nonathlete comparison groups, and determine the impact of
      nutrition knowledge on dietary intake. METHODS: An extensive literature search
      from the earliest record to March 2010 using the terms nutrition knowledge or
      diet knowledge and athlete or sport was conducted. Included studies recruited
      able or physically disabled, male or female, competitive (recreational or elite)
      athletes over the age of 13 yr. Quantitative assessment of knowledge and, if
      available, diet intake was required. Because of variability in the assessment of
      nutrition knowledge and dietary intake, meta-analysis was not conducted. RESULTS:
      Twenty-nine studies (17 published before 2000) measuring nutrition knowledge (7
      including a nonathlete comparison group) met inclusion criteria. Athletes'
      knowledge was equal to or better than that of nonathletes but lower than
      comparison groups including nutrition students. When found statistically
      significant, knowledge was greater in females than males. A weak (r < .44),
      positive association between knowledge and dietary intake was reported in 5 of 9
      studies assessing this. Common flaws in articles included inadequate statistical
      reporting, instrument validation, and benchmarking. CONCLUSION: The nutrition
      knowledge of athletes and its impact on their dietary intake is equivocal. There
      is a need for high-quality, contemporary research using validated tools to
      measure nutrition knowledge and its impact on dietary intake.

PMID- 21719907
TI  - [Selection of surgical approach to orbital tumors based on differential
      diagnosis].

PMID- 21719908
TI  - [Threshold levels of intracranial pressure as determinants of survival from
      diffuse brain injury. An observational study].
AB  - OBJECTIVE: Intracranial pressure (ICP) is frequently monitored in patients with
      severe head injuries. In this study of a series of diffuse brain injury patients,
      we investigated whether there are significant threshold levels that determine the
      outcome. METHOD: Data were obtained from 17 patients with severe head injuries
      (adults aged >= 15-years-old). The outcome was categorized using the Glasgow
      Outcome Scale and survival or death. Patients were also grouped according to the
      Traumatic Coma Data Bank (TCDB) CT classification for diffuse injury: type I
      (n=0); II (n=5); III (n=10); IV (n=2). CONCLUSION AND RESULT: The mortality rate
      was 29% (5 of 17 patients). The average initial ICP within 24 hours (14.08 mmHg)
      and the peak ICP (26.75 mmHg) were lower in the survivors than that in the
      patients who died (57.60 mmHg and 91.00 mmHg, respectively; p=0.0006 and 0.0002,
      respectively). Patients with an initial ICP score>35 mmHg did not survive, and
      patients with a peak ICP<35 mmHg, except one who died of a traumatic brainstem
      hemorrhage, did survive. Using an X-bar chart, a threshold value for the initial
      ICP within 24 hours of 27 mmHg and for the peak ICP 46 mmHg appear to be the
      survival predictors in patients with diffuse brain injury.

PMID- 21719909
TI  - [Intracranial metastasis of thymoma: report of three cases].
AB  - Thymoma with metastasis to the central nervous system is extremely rare. Herein,
      three rare cases of thymoma with intracranial metastasis are reported. Case 1
      (thymoma, B3 in the WHO classification); cranial magnetic resonance imaging (MRI)
      revealed a mass lesion with a ring enhancement effect in the right temporal lobe.
      The cystic and hemorrhagic lesion was subtotally removed and radiation therapy of
      40 Gy was administered to the tumor cavity containing the remains of the tumor
      around the ependyma. The patient received combination chemotherapy with
      carboplatin and gemcitabine hydrochloride, and he was discharged 3 months after
      the operation. Case 2 [(thymoma, C (thymic carcinoma)]; multiple cerebral
      metastases of 8 lesions were found and whole brain irradiation of 40 Gy was
      performed. Three months later, rapid development of 2 metastatic lesions resulted
      in the patient's death. At autopsy, neoplastic lesions were found in the neck
      lymph node, right shoulder, chest frame, pleural cavity, diaphragm, lung,
      periaortic lymph node, liver and pancreas. Case 3 (thymoma, B2); computed
      tomography (CT) scan and MRI showed a tumorous lesion over the cerebellar
      hemisphere. At operation, a vascular, elastic-soft and grey tumor was found to
      originate from the dura mater and had invaded the occipital bone. The tumor had
      also invaded the arachnoid membrane and sinus wall but the pia mater was free
      from invasion. Thereafter local irradiation of 40 Gy was performed to the tumor
      cavity containing the remains of the tumor around the sinus. However local
      recurrence reoccured 3 years later. After stereotactic irradiation of 40 Gy to
      the recurrent tumor, the tumor diminished. The patient is wheelchair-bound 3
      years and 4 months after the operation. Most cerebral metastases are extremely
      rare. Outcome remains poor and life expectancy is very short when brain
      metastasis is present. Treatment for thymoma is multimodal, including surgery,
      irradiation and chemotherapy.

PMID- 21719910
TI  - [A case of intramedullary spinal cord metastasis from breast carcinoma: surgical
      resection for conus medullaris lesion].
AB  - A 46-year-old female presented with gait disturbance and urinary retention which
      had exacerbated over 3 weeks. The patient had a medical history of breast cancer
      and brain metastases that had been well controlled by serial chemotherapy and
      gamma knife irradiation, and had remained independent with Karnofsky performance
      status (KPS) score of 100 %. On admission, neurological examination detected mild
      sensorimotor disturbance in the right lower extremity and hypesthesia in the
      perianal region, in addition to urinary retention and decreased anal tone. Spinal
      MR imaging demonstrated a well demarcated, heterogeneously enhanced,
      intramedullary tumor at the L1 level, appearing as isointense on both T1 and T2
      weighted images. The patient underwent subtotal tumor resection via
      hemilaminectomy at the L1 and L2 levels. Postoperatively, the patient's motor
      weakness and vesicorectal dysfunction showed remarkable improvement, whereas
      sensory disturbance was only very slightly improved. Histological findings of the
      tumor were consistent with metastatic breast carcinoma. Surgical resection can be
      considered for the treatment of intramedullary spinal cord metastasis if the
      lesion is located in the conus medullaris.

PMID- 21719911
TI  - [Ruptured aneurysm at the anterior wall of the internal carotid artery in a
      patient with systemic lupus erythematosus and secondary antiphospholipid
      syndrome].
AB  - A 60 year-old woman, who had a 45-year history of systemic lupus erythematosus
      (SLE) and secondary antiphospholipid syndrome, presented with subarachnoid
      hemorrhage due to a ruptured aneurysm at the anterior wall of the non-branching
      site of the right internal carotid artery. She underwent radical surgery on the
      day of onset. In light of the possibility of arterial dissection, we performed
      extracranial-intracranial bypass prior to careful exploration of the aneurysm.
      Based on the finding of saccular aneurysm, she ultimately underwent neck clipping
      of the aneurysm without complication. Postoperative course was uneventful, and
      she did not suffer from cerebral vasospasm. We recommend early surgical
      intervention in patients with aneurysmal SAH associated with SLE, while intrinsic
      pathologies of SLE such as fragile vascular structure and the risk for ischemic
      complication should be considered.

PMID- 21719912
TI  - [Asymptomatic intracerebral hemorrhage under strict blood pressure control due to
      postoperative cerebral hyperperfusion in a patient with moyamoya disease].
AB  - We report a case of moyamoya disease manifesting as asymptomatic intracerebral
      hemorrhage due to postoperative cerebral hyperperfusion, despite the prophylactic
      intensive blood pressure control. This 35-year-old man initially suffered from
      right upper quadrantanopsia and was found to have cerebral infarction in the left
      occipital lobe due to moyamoya disease. He also manifested preoperatively a small
      intracerebral hemorrhage at the left caudate nucleus. The left cerebral
      hemisphere showed apparent hemodynamic compromise, thus he underwent left
      superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with
      indirect pial synangiosis. He was subjected to prophylactic strict blood pressure
      control postoperatively to avoid hyperperfusion syndrome. The N-isopropyl-p
      <sup>123</sup>I-Iodoamphetamine SPECT (<sup>123</sup>I-IMP-SPECT) 1 day after
      surgery showed intense increase in cerebral blood flow (CBF) at the site of the
      anastomosis, and further blood pressure lowering was attempted. He did not suffer
      from neurologic deterioration during the postoperative period, while computed
      tomography (CT) 7 days after surgery revealed asymptomatic intracerebral hematoma
      (ICH) at the subcortex under the site of the anastomosis. Cerebral hyperperfusion
      is a potential complication of revascularization surgery for moyamoya disease.
      Accurate diagnosis and proper management of hyperperfusion are essential to avoid
      deleterious neurologic event due to hyperperfusion.

PMID- 21719913
TI  - [A case of cavernous sinus dural arteriovenous fistula presenting with
      intracranial hemorrhage].
AB  - Intracranial cavernous sinus dural arteriovenous fistula (CS-dAVF) rarely causes
      intracranial hemorrhage. We report a case of CS-dAVF presenting with intracranial
      hemorrhage. A 62-year-old man presented tonic clonic convulsion with
      consciousness disturbance and was transferred to our hospital. CT scan revealed
      subarachnoid hemorrhage and right frontal subcortical hemorrhage. Angiography
      revealed right CS-dAVF which drained only into the vein of the right sylvian
      fissure. Transvenous embolization was performed using detachable coils. After
      embolization, CS-dAVF had completely disappeared and the patient was discharged
      without any symptom. We summarized the fourteen reported cases, including ours,
      of CS-dAVF with intracranial hemorrhage. All of them had retrograde drainage
      through cerebral veins.

PMID- 21719914
TI  - [Observation of de novo formation and growth of an intracranial aneurysm: a case
      report].
AB  - We observed a de novo formation and growth of an aneurysm in a 43-year-old woman
      who was followed up after treatment of a subarachnoid hemorrhage (SAH). In 2002,
      the patient, whose mother had a history of SAH, presented with SAH at the age of
      36. Three-dimensional computed tomography angiography (3D-CTA) and digital
      subtraction angiography showed an aneurysm in the right internal carotid
      posterior communicating artery. The aneurysm was clipped and postoperative course
      was uneventful without neurological deficit. The patient was followed up by 3D
      CTA and magnetic resonance angiography every 6 months, because of an untreated
      small aneurysm, 3 mm in diameter, in the left middle cerebral artery (MCA). The
      MCA aneurysm remained unchanged but a de novo aneurysm, 1.5 mm in diameter,
      developed in the right anterior cerebral artery (ACA) 6 years after the first
      surgery. The ACA aneurysm grew to 4 mm in diameter during the following 10 months
      but the MCA aneurysm remained unchanged. Both aneurysms were clipped in one
      session. The MCA aneurysm had a smooth wall but the ACA aneurysm had an irregular
      and thin wall. The postoperative course was uneventful. Young female patients who
      have developed SAH with familial history, like this case, should receive long
      term follow up to check whether a de novo aneurysm has developed.

PMID- 21719915
TI  - [Congenital anomalies in the central nervous system(8)Dandy-Walker syndrome].

PMID- 21719916
TI  - Allogeneic adoptive cell transfer therapy as a potent universal treatment for
      cancer.

PMID- 21719917
TI  - Negative electron transfer dissociation Fourier transform mass spectrometry of
      glycosaminoglycan carbohydrates.
AB  - Electron transfer through gas phase ion-ion reactions has led to the widespread
      application of electron- based techniques once only capable in ion trapping mass
      spectrometers. Although any mass analyzer can in theory be coupled to an ion-ion
      reaction device (typically a 3-D ion trap), some systems of interest exceed the
      capabilities of most mass spectrometers. This case is particularly true in the
      structural characterization of glycosaminoglycan (GAG) oligosaccharides. To
      adequately characterize highly sulfated GAGs or oligosaccharides above the
      tetrasaccharide level, a high resolution mass analyzer is required. To extend
      previous efforts on an ion trap mass spectrometer, negative electron transfer
      dissociation coupled with a Fourier transform ion cyclotron resonance mass
      spectrometer has been applied to increasingly sulfated heparan sulfate and
      heparin tetrasaccharides as well as a dermatan sulfate octasaccharide. Results
      similar to those obtained by electron detachment dissociation are observed.

PMID- 21719918
TI  - Identification of amino acid phosphorodiamidates of antiviral nucleosides using
      electrospray ionization tandem mass spectrometry.
AB  - Several amino acid phosphorodiamidate derivatives of d4T as anti-HIV prodrugs
      were synthesized and investigated using electrospray ionization multistage tandem
      mass spectrometry (ESI-MS(n)). A novel methyl group migration in gas phase was
      observed in ESI-MS(2) of the sodium adducts of amino acid methyl ester of
      phosphorodiamidates of 2',3'-didehydro-2',3'-dideoxythymidine (d4T). The proposed
      structures of the rearrangement ions were confirmed by high resolution tandem
      mass spectrometry. A possible mechanism involving the pentacoordinate phosphoric
      carboxylic phosphate anhydride was proposed, in which a seven-membered ring
      intermediate was formed by coordination with the metal ion between the phosphoryl
      group and carbonyl oxygen atom. Thus, the intrinsic properties of phosphoryl
      group might be the key factors responsible for this migration.

PMID- 21719919
TI  - Some thoughts on electrospray ionization mechanisms.
AB  - Electrospray ionization (ESI) mechanisms are highly complex, due to a series of
      physical and chemical phenomena taking place on a complex system, as a solution
      is. In fact, even if the solution of an analyte in a protic medium can be
      considered at first sight to be a two-component system, the presence of solvent
      dissociation equilibria and the possible interactions solvent-solvent
      dissociation products, solvent dissociation products-analyte make this system
      highly complex, also for the presence of possible ionic compounds (for example,
      Na(+), K(+)) which strongly affect the above equilibria. A high number of
      research articles have been published, mainly devoted to charged droplet
      production and to gas-phase ion generation. They all show the high complexity of
      the processes affecting electrospray measurements related to either the chemical
      equilibria present in the condensed phase and to electrolysis processes at the
      emitter tip or to the processes occurring in the sprayed droplets. As a result,
      the chemical composition inside the small droplets from which the analyte ions
      are generated can be significantly different from those in sprayed solution. In
      this review, after a short survey of the proposed ESI mechanisms, some
      experiments are described. They were performed to examine if ion mobility in
      solution, before the formation of the sprayed charged droplets, can affect the
      ESI results. The data, obtained by studying both inorganic and organic analytes,
      indicate that the ESI spectra are dependent on the analyte dimension and charge
      state which, as a consequence, affect their ion mobility in solution.

PMID- 21719920
TI  - Photoionization study of L-valine in the gas phase by vacuum ultraviolet
      synchrotron radiation.
AB  - The photoionization and photodissociation of L-valine are studied by tunable
      synchrotron vacuum ultraviolet photoionization mass spectrometry at the photon
      energy of 13 eV. The ionization energy of L-valine and the appearance energies of
      major fragments are measured by the photoionization efficiency spectrum in the
      photon energy range of 8-11 eV. Possible formation pathways of the major
      fragments, NH(2)CHC(OH)(2)(+) (m/z=75), NH(2)(CH(3))(2)(CH)(2)(+) (m/z=72) and
      NH(2)CHCO(+) (m/z=57), are discussed in detail with the theoretical calculations
      at the B3LYP/6-31++G (d, p) level. Hydrogen migration is considered as the key
      way for the formation of NH(2)CHC(OH)(2)(+) (m/z=75) and NH(2)CHCO(+) (m/z=57).
      Furthermore, other fragments, NH(2)CHCOOH(+) (m/z=74), (CH(3))(2)(CH)(2)(+)
      (m/z=56), C(4)H(7)(+) (m/z=55), NH(2)CHOH(+) (m/z=46), NH(2)CH(2)(+) (m/z=30) and
      m/z=18, species are also briefly described.

PMID- 21719921
TI  - Targeted and non-targeted boron complex formation followed by electrospray
      Fourier transform ion cyclotron mass spectrometry: a novel approach for
      identifying boron esters with natural organic matter.
AB  - The formation of boron esters was investigated in peat-soluble humified materials
      with a detailed molecular-level description of boron-organic interactions.
      Thousands of individually baseline separated signals were obtained from the
      analysis of natural organic matter of peat samples, using Fourier transform ion
      cyclotron resonance mass spectrometry. This technique offers unsurpassed isotope
      specific mass resolution that can lead to precise molecular formula assignments
      by means of mathematical data analysis and visualisation techniques, such as mass
      defect (Kendrick) or elemental ratio (van Krevelen) plots. The analysis of
      potential boron binding structures within the sample of natural organic matter
      was described based on prior results. Herein, we describe an algorithm that can
      be used to effectively distinguish and filter complexes through data obtained
      from boron-enriched systems with highly intricate mass spectra, such as natural
      organic matter.

PMID- 21719922
TI  - Determination of heats of tautomerization nitrile-ketenimine by mass
      spectrometry.
AB  - Tautomerism of some nitriles has been studied by mass spectrometry. The analysis
      of the corresponding mass spectra has allowed to assign some fragmentations to
      specific tautomers and to determine heats of tautomerization through temperature
      effects and electron energy studies. Experimental determinations are supported by
      theoretical calculations. The joint analysis of mass spectrometry and DFT-B3LYP
      data indicate that this tautomeric equilibrium can be studied by the experimental
      spectrometric strategy employed.

PMID- 21719923
TI  - Investigation of coordination of Mg(II) cations to 2-pyrimidinyloxy-N
      arylbenzylamines by electrospray mass spectrometry: insights for Mg(II) catalyzed
      Smiles rearrangement reactions.
AB  - The CH(3)OH solutions of pyrimidinyloxy-N-arylbenzylamines (1-5) in the presence
      of Mg(II)X(2) salts (X = Cl or ClO(4)) were investigated by electrospray
      ionization mass spectrometry and tandem mass spectrometry (MS/MS) subsequently,
      showing that the cationic Mg(II) complexes 1-5.MgX(+) were important active
      complexes or intermediates for initiating interesting Smiles rearrangement
      reactions in both the gas and solution phases. By using different MgX(2) salts
      and selecting a set of reactants with different substitutes, the role of the
      counter-ion (X(-)) and the structure effect of the reactants on the Mg(II)
      catalyzed Smiles rearrangement reactions were studied. Moreover, the solvent
      effect on Mg(II) catalyzed Smiles rearrangement reactions was revealed by
      studying the CH(3)OH adduct complexes of 1-5.MgCl(+), which showed that the
      coordination of CH(3)OH to the Mg(II) center in the complexes decreased the
      reaction tendency. The mechanisms involved in the gas-phase Mg(II) catalyzed
      Smiles rearrangement reactions were proposed on the basis of MS/MS experiments
      and theoretical computations, showing some unique chemistries initiated by
      introducing Mg(II) into the template molecules.

PMID- 21719924
TI  - Intercluster reactions show that (CH3)2S(+)CH2CO2H is a better methyl cation
      donor than (CH3)3N(+)CH2CO2H.
AB  - The intrinsic methylating abilities of the known biological methylating
      zwitterionic agents, dimethylsulfonioacetate (DMSA), (CH(3))(2)S+CH(2)CO(2)(-)
      (1) and glycine betaine (GB), (CH(3))(3)N+CH(2)CO(2)(-) (2), have been examined
      via a range of gas phase experiments involving collision-induced dissociation
      (CID) of their proton-bound homo- and heterodimers, including those containing
      the amino acid arginine. The relative yields of the products of methyl cation
      transfer are consistent in all cases and show that protonated DMSA is a more
      potent methylating agent than protonated GB. Since methylation can occur at more
      than one site in arginine, the [M+CH(3)](+) ion of arginine, formed from the
      heterocluster [DMSA+Arg+H](+), was subject to an additional stage of CID. The
      resultant CID spectrum is virtually identical to that of an authentic sample of
      protonated arginine-O-methyl ester but is significantly different to that of an
      authentic sample of protonated N(G)-methyl arginine. This suggests that
      methylation has occurred within a salt bridge complex of [DMSA+Arg+H](+), in
      which the arginine exists in the zwitterionic form. Finally, density functional
      theory calculations on the model salts, (CH(3)CO(2)(-))[(CH(3))(3)S(+)] and
      (CH(3)CO(2)(-))[(CH(3))(4)N(+)], show that methylation of CH(3)CO(2)(-) by
      (CH(3))(3)S(+) is both kinetically and thermodynamically preferred over
      methylation by (CH(3))(4)N(+).

PMID- 21719925
TI  - Chiral discrimination of drugs by DNA tetranucleotides under electrospray
      ionisation conditions.
AB  - The DNA tetranucleotides, extended versions of GCA at the 3'-end or 5'-end, were
      used as chiral selectors for the chiral discrimination of atenolol, DOPA,
      tamsulosin, valacyclovir and zolmitriptan. Chiral discrimination was achieved by
      investigating the collision-induced dissociation spectra of the [X+Y-2H](2-) ion
      generated by electrospraying a solution mixture of tetranucleotide (X) and R- or
      S-analyte drug (Y). The relative abundances of the precursor ion and the product
      ion, resulting from the loss of drug, were considered for measuring the degree of
      chiral discrimination. Among all the tetranucleotides studied, AGCA showed the
      highest chiral discrimination. The present study emphasised the position of an
      adenine base in the tetranucleotide in chiral discrimination. The suitability of
      the method for the measurement of optical purity was also demonstrated in the
      case of zolmitriptan.

PMID- 21719926
TI  - Maternal risk factors associated with term low birth weight neonates: a matched
      pair case control study.
AB  - OBJECTIVE: To study maternal risk factors associated with full term low birth
      weight (LBW) neonates. DESIGN: Matched pair case control study. SETTING:
      Multicenter study including 2 medical colleges and 1 civil hospital, between July
      2009 to December 2009. PATIENTS: Of 2382 neonates screened, 274 full term LBW
      babies (of 638) and 274 pair matched controls (of 1744) were included in the
      study. 364 LBW babies were excluded because of premature delivery/gestational age
      not known (314), unavailability of suitable matched controls (18), and
      insufficient data (32). METHODS: Maternal factors including birth spacing,
      height, pre-delivery weight and pregnancy weight gain, age, parity, educational
      and economic status, type of family, antenatal care (ANC), maternal exposure to
      tobacco, hypertension and anemia were studied. RESULTS: Birth spacing <36 months,
      maternal height <= 145 cm, pre-delivery weight <= 55 kg, pregnancy weight gain <6
      kg, exposure to tobacco, inadequate antenatal care, maternal hypertension, low
      socio-economic status, maternal anemia and less maternal education were
      associated with delivery of a low birth weight infants. Conditional logistic
      regression analysis showed that significant risk factors associated with low
      birth weight were inadequate ANC (OR-4.98, 95% CI-2.64 to 9.39), maternal weight
      before delivery <= 55 kg (OR-4.81, 95% CI-2.53 to 9.15) and height <= 145 cm (OR
      4.13, 95% CI-2.04 to 8.37). CONCLUSION: Maternal malnutrition, inadequate
      antenatal care and poor weight gain during pregnancy are significant predictors
      for delivery of a low birth weight neonate.

PMID- 21719927
TI  - Clinical profile of mood disorders in children.
AB  - OBJECTIVE: To described the clinical profile of pediatric mood disorders. DESIGN:
      Retrospective record review; Ages <= 16 y. SETTING: Tertiary case hospital.
      PARTICIPANTS: Children <= 16 year with a DSM-IV diagnosis of Mood disorders.
      METHODS: Records were screened for the period between June 1, 2008 and May 31,
      2010. RESULTS: The prevalence of mood disorders was 4.1% (38/930). Mood was
      depressed in 51.9% and irritable in 33.3% of depressive disorders. Other common
      symptoms were anhedonia, sleep or appetite disturbances, concentration difficulty
      and anxiety. Nearly 13.2% had suicidal ideation and 28.5% had comorbid
      psychiatric disorder. Family history was positive in 39.5%, while an identifiable
      stressor was present in 50%. CONCLUSIONS: The pediatric mood disorders have a
      unique clinical presentation and requires more research, especially from Indian
      setting.

PMID- 21719928
TI  - Iron deficiency as a risk factor for simple febrile seizures--a case control
      study.
AB  - OBJECTIVE: To study the role of iron deficiency as a risk factor for simple
      febrile seizures. DESIGN: Case control study. SETTING: Pediatric department of a
      tertiary care teaching hospital. PARTICIPANTS: 154 cases and 154 controls were
      included in the study. Consecutive cases and concurrent controls were selected.
      Cases were children of age group 6 months to 3 years presenting with simple
      febrile seizures. Controls were children of same age group presenting with short
      febrile illness but without any seizures. METHODS: After informed consent,
      detailed history was taken and clinical examination done in both cases and
      controls and blood investigations were done to diagnose iron-deficiency in both
      cases and controls. Iron deficiency was diagnosed as per WHO criteria (hemoglobin
      value <11 g%, red cell distribution width of >15% and serum ferritin value <12
      ng/mL). Other explanatory variables, which can be the potential confounders were
      also included in the study and considered for analysis. RESULTS: Highly
      significant association was found between iron deficiency and simple febrile
      seizures in both univariate and multivariate analysis. Crude odds ratio was 5.34
      (CI 3.27- 8.73, P<0.001) and adjusted odds ratio in the logistic regression
      analysis was 4.5 (CI 2.69- 7.53, P <0.001). CONCLUSIONS: Iron deficiency is a
      significant risk factor for simple febrile seizures in children of age group 6
      months to 3 years.

PMID- 21719929
TI  - Risk factors for perinatal mortality due to asphyxia among emergency obstetric
      referrals in a tertiary hospital.
AB  - OBJECTIVES: To evaluate the clinical, behavioral and health-care associated risk
      factors of intrapartum perinatal mortality (IPPM). DESIGN: Prospective cohort
      study. SETTING: Labor room and postnatal wards of a teaching hospital in North
      India. PARTICIPANTS: Pregnant women were eligible for enrollment in the study if
      period of gestation at delivery was 35 weeks or more or baby weighed at least
      2000 g at birth, index pregnancy was not booked in antenatal clinic of the study
      hospital and fetus was delivered within 24 h of admission in the hospital.
      METHODS: Information about antenatal care and events surrounding labor and
      delivery were retrieved from antenatal care records, referral notes, hospital
      clinical records and interview of mothers. Multivariate analysis was conducted
      using forward stepwise logistic regression analysis. MAIN OUTCOME MEASURE: IPPM
      was defined as asphyxia-specific stillbirth or asphyxia-specific early neonatal
      death. RESULTS: Among 248 emergency obstetric referrals during the study period,
      rate of IPPM was 8% (20/248, 18 fresh stillbirths and 2 asphyxia-specific
      neonatal deaths). District hospitals and community health-centers/first referral
      units contributed three-fourths of all referrals. On logistic regression analysis
      significant risk factors for IPPM were presence of obstructed labor (OR: 23, 95%
      CI: 1.9-275.8), father engaged in unskilled labor (OR: 10, 95% CI: 1.3-77.7) and
      absence of urine examination during antenatal period (OR: 5.5, 95% CI: 1.8-16.3).
      CONCLUSIONS: Low socioeconomic status, inadequate antenatal care and poor
      intrapartum care due to unskilled birth attendance are risk factors of IPPM.

PMID- 21719930
TI  - Potential factors related to waist circumference in urban South Indian children.
AB  - OBJECTIVES: To identify important factors (linked to lifestyle, eating and
      sedentary behaviors) relating to waist circumference among urban South Indian
      children aged 3 to 16 years. DESIGN: Cross sectional. SETTING: Urban schools of
      Bangalore, from August 2008 to January 2010. PARTICIPANTS: 8444 children; 4707
      children aged 3-10 years and 3737 children aged 10-16 years. METHODS: Data were
      collected on the frequency of consumption of certain foods, physical activity
      patterns, sedentary habits at home, sleep duration and behaviors such as habits
      of snacking, skipping breakfast, eating in front of television and frequency of
      eating out. Simple linear regression analysis of waist circumference on various
      food items, physical activity, behavior and parental BMI were performed.  A path
      model was developed to identify potential causal pathways to increase in waist
      circumference. RESULTS: Increased consumption of bakery items, non vegetarian
      foods, increased television viewing, decreased sleep duration, eating while
      watching television, snacking between meals, family meals, skipping breakfast (in
      older children), and parental BMI were found to be related to waist
      circumference. Older children possibly under-reported their intake of unhealthy
      foods, but not behaviors. CONCLUSIONS: This study identified potential behaviors
      related to waist circumference in urban school children in India.  Longitudinal
      studies with better measures of morbidity and adiposity are warranted in order to
      derive casual relationships between various determinants and waist circumference.

PMID- 21719931
TI  - Body mass index cut-offs for screening for childhood overweight and obesity in
      Indian children.
AB  - OBJECTIVE: To develop age and sex specific cut offs for BMI to screen for
      overweight and obesity in Indian children linked to an adult BMI of 23 and 28
      kg/m2 respectively, using contemporary Indian data. DESIGN: Cross-sectional.
      SETTING: Multicentric, School based. PARTICIPANTS: 19834 children were measured
      from 11 affluent schools from five major geographical regions of India. Data were
      analyzed using the LMS method, which constructs growth reference percentiles
      adjusted for skewness. RESULTS: Compared to the cut-offs suggested for European
      populations and those by the  Indian Academy of Pediatrics 2007 Guidelines, the
      age and sex specific cut off points for body mass index for overweight and
      obesity for Indian children suggested by this study are lower. CONCLUSIONS:
      Contemporary cross-sectional age and sex specific BMI cut-offs for Indian
      children linked to Asian cut-offs of 23 and 28 kg/m2 for the assessment of risk
      of overweight and obesity, respectively are presented.

PMID- 21719932
TI  - Serum magnesium in overweight children.
AB  - OBJECTIVE: To determine whether overweight children and adolescents have lower
      serum concentration and lower dietary intake of magnesium compared to those with
      normal weight; and to study the correlation of serum  magnesium levels with
      components of metabolic syndrome in children and adolescents. DESIGN: Cross
      sectional, comparative study. SETTING: General/Pediatric Endocrinolgy OPD
      tertiary care medical centre. Study done from July 2007 to March 2009
      PARTICIPANTS: 55 overweight and 53 normal weight children and adolescents aged 4
      years to 14 years. METHODS: We compared fasting levels of serum magnesium,
      insulin, glucose, total and HDL-cholesterol, triglycerides and dietary magnesium
      intake. RESULTS: The serum magnesium levels were significantly lower in
      overweight (2.12 +/-; 0.33 mg/dL) compared to normal weight group (2.56 +/- 0.24
      mg/dL, P<0.001), while the dietary intake of magnesium (adjusted for calorie
      intake) was higher in overweight group (0.20 +/- 0.06 mg/kcal) compared to normal
      weight (0.17 +/- 0.05 mg/kcal; P= 0.005). Serum magnesium levels were inversely
      correlated with body mass index, systolic blood pressure, diastolic blood
      pressure, waist circumference and fasting insulin levels. CONCLUSIONS: Serum
      magnesium levels were significantly lower in overweight children compared to
      those with normal weight in spite of a higher dietary intake.

PMID- 21719933
TI  - Factors associated with mortality in under-five children with severe anemia in
      Ebonyi, Nigeria.
AB  - OBJECTIVE: To determine the risk factors associated with poor outcome among under
      five children with severe anemia in sub Saharan Africa. DESIGN: Cross-sectional.
      SETTING: University Teaching Hospital, Nigeria. PARTICIPANTS: Under-five children
      presenting with severe anemia (PCV <15%, Hb <5g/dL). METHODS: Between January and
      June 2006, children admitted with severe anemia were recruited. The biodata,
      socio-economic status, signs and symptoms were documented for each child after
      the initial stabilization. Laboratory investigations using blood, stool and urine
      samples were carried out.  Data were analyzed using SPSS version 11.0. RESULTS:
      140 out of the 1,450 patients admitted during the period of study had severe
      anemia (prevalence 9.7%). Malaria either alone or in combination was the most
      common cause of severe anemia [n=90 (64.3%)]. 117 patients (83.6%) recovered,
      while 4(2.8%) left against medical advice and 19 died (case fatality rate 13.6%).
      The variables associated with mortality were malnutrition (P=0.02), tachycardia
      (P= 0.03), coma (P<0.001), and absence of blood transfusion (P=0.001). On
      logistic regression analysis coma (P=0.002), not receiving blood transfusion
      (P=0.002) and female gender (P=0.04) predicted poor outcome. CONCLUSIONS: The
      study revealed high mortality rates among under-five children with severe anemia.
      Coma, malnutrition, female gender and absence of blood transfusion were
      associated with higher mortality in severe anemia.

PMID- 21719934
TI  - Prevalence and annual risk of tuberculosis infection in rural Mysore.
AB  - We carried out a tuberculin survey among 5-10 years old children in rural Mysore
      (n=1026) to estimate the annual risk of tuberculosis infection (ARTI). 90.8% of 
      them  had  BCG scar. The prevalence of infection was estimated  as 13.3% with 95%
      CI of 11.4-15.5 and ARTI  as  1.38%. These figures are comparatively higher than
      what is reported from other places in India.

PMID- 21719935
TI  - Vitamin E supplementation in exclusively breastfed VLBW infants.
AB  - We conducted this study to evaluate the adequacy of breastmilk as a source of
      vitamin E in exclusively breastfed VLBW infants. Such infants (n=44) were
      randomly allotted to receive vitamin E supplementation (n = 23); the rest (n =
      21) did not receive vitamin E.   After 21 days,  the vitamin E level in the
      supplemented group was 0.78 + 0.26 mg/dL as compared to 0.77+ 0.25 mg/dL in the
      unsupplemented group (P=0.69).  The ratio of Vitamin E to lipids was also
      comparable in the two groups, (P=0.65).  We concluded that vitamin E
      supplementation is not routinely needed in VLBW infants.

PMID- 21719936
TI  - ASHAs involvement in newborn care: a feasibility study.
AB  - We assessed the feasibility of involvement of Accredited Social Health Activist
      (ASHA) in newborn care. All the ASHAs (n = 33) of PHC Dayalpur, Faridabad
      district of Haryana were trained for one day which was followed by two refresher
      trainings. The mean (SD) knowledge score (out of 11) of ASHAs were 6.45 (2.44),
      6.50 (2.01), 7.45 (1.36) and 7.15 (1.27) at pre-training, immediately after
      training, and after three and six months, respectively. Four fifth (83%) of the
      newborns born at home were weighed within 3 days of birth. About half (44%) of
      ASHAs weighed the neonates within +/- 250 grams of the weight recorded by the
      author. We conclude that ASHAs could be involved in providing care for newborn.
      However, such efforts should ensure a stronger focus on skill development and
      practical experience.

PMID- 21719937
TI  - Clinical profile of leukocyte adhesion deficiency type I.
AB  - Leukocyte adhesion deficiency type I (LAD-I) is a rare, inherited
      immunodeficiency with defect in the recruitment of leukocyte to the site of
      inflammation.  Patients with severe LAD-I have absent or markedly reduced
      expression of CD18 and CD11. Here we report clinical profile of 7 cases of LAD-I
      diagnosed at our center over a period of 3 years.  Recurrent skin and mucous
      membrane infections were the major presenting manifestations.  All children had a
      history of delayed cord separation.

PMID- 21719938
TI  - Outbreak of Sphingomonas paucimobilis septicemia in a neonatal intensive care
      unit.
AB  - We describe an outbreak of Sphingomonas paucimobilis in 13 newborn infants with
      septicemia and septic shock. Fifteen available isolates were obtained from
      patients and distilled water. Pulsed field gel electrophoresis showed that there
      was a cross-transmission of S. paucimobilis in eleven patients but these types
      were not the same the isolate obtained from the distilled water. The outbreak was
      terminated by taking appropriate control measures for infection and change of
      source of distilled water.

PMID- 21719939
TI  - Quality of life in children with epilepsy.
AB  - Quality of life was assessed in 108 epileptic children (6-15 years) using a hindi
      translation of Quality of Life in Children with Epilepsy (QOLCE) questionnaire.
      The questionnaire  consist of 76 items with 16 subscales covering five domains of
      life: physical function, social function, cognition, emotional and behavioral
      well being. Overall score was 62.62+/-21.32. Chronbachs-a for all 13 multi-item
      subscales was above 0.70, indicating good internal consistency and reliability.
      Pearson correlation revealed good construct validity. Overall quality of life was
      affected by age, type of epilepsy, seizure frequency and maternal education
      (P<0.05). Energy levels, language and attention (P<0.05) were better in older
      children whereas younger children had better self esteem and lower levels of
      anxiety. Seizure frequency compromised all fields except stigma, attention, and
      energy levels (P>0.05).

PMID- 21719940
TI  - Risk factors for prolonged shedding of 2009 H1N1 influenza virus.
AB  - This retrospective study was conducted to estimate the shedding of 2009 H1N1
      virus and the risk analysis by review of medical charts, laboratory and
      radiological findings of all inpatients with confirmed pandemic influenza A
      (H1N1) at a provincial pediatric hospital. A total of 41 cases attending the
      inpatient department between 15 November, 2009 to 14 December, 2009 were
      included. Prolonged and discontinuous shedding of 2009 H1N1 virus (median, 10
      days; range, 2 to 24 days) were detected by real-time RT-PCR. The interval from
      onset of symptom to the start of oseltamivir therapy was an independent risk
      factor for prolonged virus shedding.

PMID- 21719941
TI  - Longitudinal growth of infants in Qatar: comparison with WHO and CDC growth
      standards.
AB  - Longitudinal growth data for infants in Qatar were compared to growth standards
      published by the CDC and WHO. 300 randomly selected full-term normal infants (150
      males, 150 females) in Qatar were followed-up and weight and length were
      sequentially recorded at 2 months, 4 months, 6 months, 12 months and 18 months
      age. The mean length for age of girls was higher than those published by the CDC
      and WHO at 12 and 18 months of age.  Using the CDC standard for weight for length
      detected more wasted infants (9.0% and 6.5%) compared to using WHO standards
      (6.27% and 6.0%) for males and females, respectively. When WHO and CDC standards
      are compared, more infants were identified as overweight when the former were
      used. The WHO standards are preferable because they are based on a leaner
      breastfed reference and because overweight is likely to be a greater problem in
      Qatar in the future.

PMID- 21719942
TI  - Management of lower limb deformities in children with osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) often leads to severe lower limb (LL) deformities
      due to recurrent fractures that significantly hamper ambulation. We describe our
      management experience of correction of LL deformities in four children with OI.
      Medical management consisted of peri and postoperative pamidronate therapy,
      calcium supplementation and rehabilitative care. Deformities were corrected with
      multiple osteotomies and intramedullary fixation by titanium elastic nails. At a
      mean follow-up of 30 months, all children have significantly reduced fracture
      incidence and have no evidence of recurrence of deformities with improved
      ambulatory status. We emphasize the importance of combined medical and surgical
      therapy for these patients.

PMID- 21719943
TI  - An observational, health service based survey for missed opportunities for
      immunization.
AB  - Studies cite missed opportunities for immunization (MOI) as a contributor to
      under-vaccination. The present prospective survey aimed at determining the
      magnitude of MOI, its contribution to under-vaccination, and identifying risk
      factors for MOI. Mothers of 1384 indoor patients L6 years were interviewed. There
      were 266 (19.2%) children with MOI, accounting for 79.6% of under-vaccination and
      93% of under-vaccination time. MOI occurred significantly more often with home
      delivery (P <0.001, Odds ratio 5.1), incomplete or incorrect maternal knowledge
      of immunization (P=0.001, Odds ratio 4.8) and, general practice and non
      Pediatric/non-Medical college based practice (P=0.001, Odds ratio 4.0). The
      impact of sociodemographic factors on likelihood of MOI was not significant.

PMID- 21719944
TI  - Ventilator-associated Acinetobacter baumannii pneumonia.
AB  - We report an outbreak of ventilator-associated pneumonia caused by carbapenem
      resistant Acinetobacter baumannii in 6 infants with acute lower respiratory tract
      infection.   Non-bronchoscopic bronchoalveolar lavage isolated A. baumannii in
      all these infants. Environmental microbiological survey of the Pediatric
      intensive care unit and pediatric wards identified oxygen humidifying chambers as
      the source of Acinetobacter. Practices of cleaning and changing of the
      humidifiers were reviewed and the outbreak was controlled with new
      recommendations.

PMID- 21719945
TI  - Respiratory motion blur identification and reduction in ungated thoracic PET
      imaging.
AB  - Respiratory motion results in significant motion blur in thoracic positron
      emission tomography (PET) imaging. Existing approaches to correct the blurring
      artifact involve acquiring the images in gated mode and using complicated
      reconstruction algorithms. In this paper, we propose a post-reconstruction
      framework to estimate respiratory motion and reduce the motion blur of PET images
      acquired in ungated mode. Our method includes two steps: one is to use minmax
      directional derivative analysis and local auto-correlation analysis to identify
      the two parameters blur direction and blur extent, respectively, and another is
      to employ WRL, a trous wavelet-denoising modified Richardson-Lucy (RL)
      deconvolution, to reduce the motion blur based on identified parameters. The
      mobile phantom data were first used to test the method before it was applied to
      32 cases of clinical lung tumor PET data. Results showed that the blur extent of
      phantom images in different directions was accurately identified, and WRL can
      remove the majority of motion blur within ten iterations. The blur extent of
      clinical images was estimated to be 12.1 +/- 3.7 mm in the direction of 74 +/- 3
      degrees  relative to the image horizontal axis. The quality of clinical images
      was significantly improved, both from visual inspection and quantitative
      evaluation after deconvolution. It was demonstrated that WRL outperforms RL and a
      Wiener filter in reducing the motion blur with one to two more iterations. The
      proposed method is easy to implement and thus could be a useful tool to reduce
      the effect of respiration in ungated thoracic PET imaging.

PMID- 21719946
TI  - A method to correct for stray light in telecentric optical-CT imaging of
      radiochromic dosimeters.
AB  - Radiochromic plastic and gel materials have recently emerged which can yield 3D
      dose information over clinical volumes in high resolution. These dosimeters can
      provide a much more comprehensive verification of complex radiation therapy
      treatments than can be achieved by conventional planar and point dosimeters. To
      achieve full clinical potential, these dosimeters require a fast and accurate
      read-out technology. Broad-beam optical-computed tomography (optical-CT) systems
      have shown promise, but can be sensitive to stray light artifacts originating in
      the imaging chain. In this work we present and evaluate a method to correct for
      stray light artifacts by deconvolving a measured, spatially invariant, point
      spread function (PSF). The correction was developed for the DLOS (Duke large
      field-of-view optical-CT scanner) in conjunction with radiochromic PRESAGE(r)
      dosimeters. The PSF was constructed from a series of acquisitions of projection
      images of various sized apertures placed in the optical imaging chain. Images
      were acquired with a range of exposure times, and for a range of aperture sizes
      (0.2-11 mm). The PSF is investigated under a variety of conditions, and found to
      be robust and spatially invariant, key factors enabling the viability of the
      deconvolution approach. The spatial invariance and robustness of the PSF are
      facilitated by telecentric imaging, which produces a collimated light beam and
      removes stray light originating upstream of the imaging lens. The telecentric
      capability of the DLOS therefore represents a significant advantage, both in
      keeping stray light levels to a minimum and enabling viability of an accurate PSF
      deconvolution method to correct for the residual. The performance of the
      correction method was evaluated on projection images containing known optical
      density variations, and also on known 3D dose distributions. The method is shown
      to accurately account for stray light on small field dosimetry with corrections
      up to 3% in magnitude shown here although corrections of >10% have been observed
      in extreme cases. The dominant source of stray light was found to be within the
      imaging lens. Correcting for stray light extended the dynamic range of the system
      from ~30 to ~60 dB. The correction should be used when measurements need to be
      accurate within 3%.

PMID- 21719947
TI  - A reconstruction method for equidistant fan beam differential phase contrast
      computed tomography.
AB  - We report a reconstruction method, called a back-projection filtered (BPF)
      algorithm, for fan beam differential phase contrast computed tomography (DPC-CT)
      with equidistant geometrical configuration. This work comprises a numerical study
      of the algorithm and its experimental verification with a three-grating
      interferometer and an x-ray tube source. The numerical simulation and
      experimental results demonstrate that the proposed method can deal with several
      classes of truncated datasets. It could be of interest in future medical phase
      contrast imaging applications.

PMID- 21719948
TI  - Terahertz-wave water concentration and distribution measurement in thin biotissue
      based on a novel sample preparation.
AB  - The measurement of water concentration and distribution in thin biotissues with
      terahertz (THz)-wave has been proposed. In this paper, a novel sample preparation
      approach was introduced to effectively preserve tissue freshness at room
      temperature. Excellent stability of this method was demonstrated by measuring the
      transmittance spectroscopy and imaging many times within a certain time.
      Moreover, the reliability of water volume concentration measurement with THz-wave
      was evaluated. Measurement results using THz-wave were in good agreement with
      volume concentration measurement results based on other quantitative methods. The
      results suggest that water concentration and distribution measurement in thin
      biotissues using THz-wave will be a potential modality for medical and biological
      diagnosis.

PMID- 21719949
TI  - Does kV-MV dual-energy computed tomography have an advantage in determining
      proton stopping power ratios in patients?
AB  - Conventional kilovoltage (kV) x-ray-based dual-energy CT (DECT) imaging using two
      different x-ray energy spectra is sensitive to image noise and beam hardening
      effects. The purpose of this study was to evaluate the theoretical advantage of
      the DECT method for determining proton stopping power ratios (SPRs) using a
      combination of kV and megavoltage (MV) x-ray energies. We investigated three
      representative x-ray energy pairs: 100 and 140 kVp comprised the kV-kV pair, 100
      kVp and 1 MV comprised the kV-MV pair, and two 1 MV x-ray beams-one with and one
      without external filtration-comprised the MV-MV pair. The SPRs of 34 human
      tissues were determined using the DECT method with these three x-ray energy
      pairs. Small perturbations were introduced into the CT numbers and x-ray spectra
      used for the DECT calculation to simulate the effects of random noise and beam
      hardening. An error propagation analysis was performed on the DECT calculation
      algorithm to investigate the propagation of CT number uncertainty to final SPR
      estimation and to suggest the best x-ray energy combination. We found that the
      DECT method using each of the three beam pairs achieved similar accuracy in
      determining the SPRs of human tissues in ideal conditions. However, when CT
      number uncertainties and artifacts such as imaging noise and beam hardening
      effects were considered, the kV-MV DECT improved the accuracy of SPR estimation
      substantially over the kV-kV or MV-MV DECT methods. Furthermore, our error
      propagation analysis showed that the combination of 100 kVp and 1 MV beams was
      close to the optimal selection when using the DECT method to determine SPRs.
      Overall, the kV-MV combination makes the DECT method more robust in resolving the
      effective atomic numbers for biological tissues than the traditional kV-kV DECT
      method.

PMID- 21719950
TI  - Comparative study of a low-Z cone-beam computed tomography system.
AB  - Computed tomography images have been acquired using an experimental (low atomic
      number (Z) insert) megavoltage cone-beam imaging system. These images have been
      compared with standard megavoltage and kilovoltage imaging systems. The
      experimental system requires a simple modification to the 4 MeV electron beam
      from an Elekta Precise linac. Low-energy photons are produced in the standard
      medium-Z electron window and a low-Z carbon electron absorber located after the
      window. The carbon electron absorber produces photons as well as ensuring that
      all remaining electrons from the source are removed. A detector sensitive to
      diagnostic x-ray energies is also employed. Quantitative assessment of cone-beam
      computed tomography (CBCT) contrast shows that the low-Z imaging system is an
      order of magnitude or more superior to a standard 6 MV imaging system. CBCT data
      with the same contrast-to-noise ratio as a kilovoltage imaging system (0.15 cGy)
      can be obtained in doses of 11 and 244 cGy for the experimental and standard 6 MV
      systems, respectively. Whilst these doses are high for everyday imaging,
      qualitative images indicate that kilovoltage like images suitable for patient
      positioning can be acquired in radiation doses of 1-8 cGy with the experimental
      low-Z system.

PMID- 21719951
TI  - Monochromatic minibeam radiotherapy: theoretical and experimental dosimetry for
      preclinical treatment plans.
AB  - Monochromatic x-ray minibeam radiotherapy is a new radiosurgery approach based on
      arrays of submillimetric interlaced planar x-ray beams. The aim of this study was
      to characterize the dose distributions obtained with this new modality when being
      used for preclinical trials. Monte Carlo simulations were performed in water
      phantoms. Percentage depth-dose curves and dose profiles were computed for single
      incidences and interleaved incidences of 80 keV planar x-ray minibeam (0.6 * 5
      mm) arrays. Peak to valley dose ratios were also computed at various depths for
      an increasing number of minibeams. 3D experimental polymer gel (nPAG) dosimetry
      measurements were performed using MRI devices designed for small animal imaging.
      These very high spatial resolution (50 um) dose maps were compared to the
      simulations. Preclinical minibeams dose distributions were fully characterized.
      Experimental dosimetry correlated well with Monte Carlo calculations (Student t
      tests: p > 0.1). F98 tumor-bearing rats were also irradiated with interleaved
      minibeams (80 keV, prescribed dose: 25 Gy). This associated preclinical trial
      serves as a proof of principle of the technique. The mean survival time of
      irradiated glioma-bearing rats increased significantly, when compared to the
      untreated animals (59.6 +/- 2.8 days versus 28.25 +/- 0.75 days, p < 0.001).

PMID- 21719959
TI  - A time-dependent embedding calculation of surface electron emission.
AB  - The Dirac-Frenkel variational principle is used to derive the embedding method
      for solving the time-dependent Schrodinger equation. Embedding allows the time
      evolution of the wavefunction to be calculated explicitly in a limited region of
      space, the region of physical interest, the embedding potential ensuring that the
      wavefunction satisfies the correct boundary conditions for matching on to the
      rest of the system. This is applied to a study of the excitation of electrons at
      a metal surface, represented by a one-dimensional model potential for Cu(111).
      Time-dependent embedding potentials are derived for replacing the bulk substrate,
      and the image potential and vacuum region outside the surface, so that the
      calculation of electron excitation by a surface perturbation can be restricted to
      the surface itself. The excitation of the Shockley surface state and a continuum
      bulk state is studied, and the time structure of the resulting currents analysed.
      There is a distinction between emission from the localized surface state, where
      the charge is steadily depleted, and the extended continuum state, where the
      current emitted into the vacuum is compensated by current approaching the surface
      from the bulk. The time taken for the current to arrive outside the surface is
      studied.

PMID- 21719960
TI  - Effect of substrate on the atomic structure and physical properties of
      thermoelectric Ca3Co4O9 thin films.
AB  - The incommensurately layered cobalt oxide Ca(3)Co(4)O(9) exhibits an unusually
      high Seebeck coefficient as a polycrystalline bulk material, making it ideally
      suited for many high temperature thermoelectric applications. In this paper, we
      investigate properties of Ca(3)Co(4)O(9) thin films grown on cubic perovskite
      SrTiO(3), LaAlO(3), and (La(0.3)Sr(0.7))(Al(0.65)Ta(0.35))O(3) substrates and on
      hexagonal Al(2)O(3) (sapphire) substrates using the pulsed laser deposition
      technique. X-ray diffraction and transmission electron microscopy analysis
      indicate strain-free growth of films, irrespective of the substrate. However,
      depending on the lattice and symmetry mismatch, defect-free growth of the
      hexagonal CoO(2) layer is stabilized only after a critical thickness and, in
      general, we observe the formation of a stable Ca(2)CoO(3) buffer layer near the
      substrate-film interface. Beyond this critical thickness, a large concentration
      of CoO(2) stacking faults is observed, possibly due to weak interlayer
      interaction in this layered material. We propose that these stacking faults have
      a significant impact on the Seebeck coefficient and we report higher values in
      thinner Ca(3)Co(4)O(9) films due to additional phonon scattering sites, necessary
      for improved thermoelectric properties.

PMID- 21719961
TI  - Room temperature one-step synthesis of microarrays of N-doped flower-like anatase
      TiO2 composed of well-defined multilayer nanoflakes by Ti anodization.
AB  - Microarrays of N-doped flower-like TiO(2) composed of well-defined multilayer
      nanoflakes were synthesized at room temperature by electrochemical anodization of
      Ti in NH(4)F aqueous solution. The TiO(2) flowers were of good anatase
      crystallinity. The effects of anodizing time, applied voltage and NH(4)F
      concentration on the flower-like morphology were systematically examined. It was
      found that the morphologies of the anodized Ti were related to the anodizing time
      and NH(4)F concentration. The size and density of the TiO(2) flowers could be
      tuned by changing the applied voltage. The obtained N-doped flower-like TiO(2)
      microarrays exhibited intense absorption in wavelengths ranging from 320 to 800
      nm. Under both UV and visible light irradiation, the photocatalytic activity of
      the N-doped flower-like TiO(2) microarrays in the oxidation of methyl orange
      showed a significant increase compared with that of commercial P25 TiO(2) film.

PMID- 21719962
TI  - Tuning color by pore depth of metal-coated porous alumina.
AB  - A simple and effective color tuning method has been developed by controlling the
      pore depth of the metal-coated porous alumina (PA) template. The mechanism for
      color tuning in this method was uncovered, which can be used to design a colorful
      complex pattern. A colorful 'world map' was produced and exhibited on a PA
      template by this method. Such vivid color tuning is predominantly due to the
      interference enhancement of the nanostructure. This method has the potential for
      tuning colors and being widely applied in the fields of nanotechnology, physics
      and photonics.

PMID- 21719963
TI  - Large-scale preparation of strawberry-like, AgNP-doped SiO2 microspheres using
      the electrospraying method.
AB  - In this paper, we report on a novel strategy for the preparation of silver
      nanoparticle-doped SiO(2) microspheres (Ag-SMSs) with an interesting strawberry
      like morphology using a simple and efficient electrospraying method. SEM
      (scanning electron microscopy), TEM (transmission electron microscopy), XRD (x
      ray diffraction), EDS (energy-dispersive spectroscopy) and UV-vis spectra
      (ultraviolet-visible spectra) were applied to investigate the morphology,
      structure, composition and optical properties of the hybrid microspheres, and E.
      coli (Escherichia coli) was used as a model microbe to evaluate their
      antibacterial ability. The results showed that the Ag-SMSs were environmentally
      stable and washing resistant. The Ag-SMSs exhibited effective inhibition against
      proliferation of E. coli, and their antibacterial ability could be well preserved
      for a long time. The environmental stability, washing resistance, efficient
      antibacterial ability and simple but productive preparation method endowed the Ag
      SMSs with great potential for practical biomedical applications.

PMID- 21719964
TI  - MOS photodetectors based on Au-nanorod doped graphene electrodes.
AB  - By using Au-nanorod (Au-NR) doped graphene as a transparent conducting electrode,
      Si-based metal-oxide-semiconductor (MOS) photodetectors (PDs) exhibit high
      external quantum efficiency (EQE) and fast response time. It is found that upon
      adding Au-NRs to the graphene, a significant increase in EQE is observed for both
      planar and Si-nanotip (Si-NT) MOS PDs. The planar Si-based MOS PDs reveal a
      notable photoresponse with an EQE of 49% at the peak wavelength of 530 nm under
      zero bias and an EQE of 66% at the peak wavelength of 600 nm under - 0.4 V bias.
      For the Si-NTs MOS PD, it exhibits a relatively high EQE of 71% under - 4 V bias
      due to the effect of light trapping arising from the nature of the Si-NT array.

PMID- 21719965
TI  - Fabrication of anion exchanger resin/nano-CdS composite photocatalyst for visible
      light RhB degradation.
AB  - A novel nanocomposite photocatalyst, D201-CdS beads (0.70-0.80 mm in diameter),
      was fabricated for visible light (lambda > 420 nm) photodegradation of Rhodamine
      B (RhB). Sphalerite CdS nanoparticles (5-15 nm) were distributed within the outer
      layer of D201 for favorable visible light permeation. Ultraviolet-visible
      spectral changes of RhB solution indicated that efficient RhB photodegradation
      was achieved by D201-CdS under visible light irradiation. More attractively,
      negligible photocorrosion of the hybrid catalyst D201-CdS was demonstrated by the
      constant photodegradation efficiency and negligible CdS leaching during five
      cycle batch runs. Besides the higher stability, D201-CdS is superior to CdS in
      terms of separation. The used nanocomposite can be readily separated from
      solutions by a simple filtration while a high speed centrifugation is needed for
      the separation of CdS. The above results suggested that the resultant D201-CdS
      nanocomposite catalyst is promising for practical application in environmental
      remediation.

PMID- 21719966
TI  - DNA abasic site-directed formation of fluorescent silver nanoclusters for
      selective nucleobase recognition.
AB  - DNA single-nucleotide polymorphism (SNP) detection has attracted much attention
      due to mutation related diseases. Various methods for SNP detection have been
      proposed and many are already in use. Here, we find that the abasic site (AP
      site) in the DNA duplex can be developed as a capping scaffold for the generation
      of fluorescent silver nanoclusters (Ag NCs). As a proof of concept, the DNA
      sequences from fragments near codon 177 of cancer supression gene p53 were used
      as a model for SNP detection by in situ formed Ag NCs. The formation of
      fluorescent Ag NCs in the AP site-containing DNA duplex is highly selective for
      cytosine facing the AP site and guanines flanking the site and can be employed in
      situ as readout for SNP detection. The fluorescent signal-on sensing for SNP
      based on this inorganic fluorophore is substantially advantageous over the
      previously reported signal-off responses using low-molecular-weight organic
      ligands. The strong dependence of fluorescent Ag NC formation on the sequences
      surrounding the AP site was successfully used to identify mutations in codon 177
      of cancer supression gene p53. We anticipate that this approach will be employed
      to develop a practical SNP detection method by locating an AP site toward the
      midway cytosine in a target strand containing more than three consecutive
      cytosines.

PMID- 21719967
TI  - Hydrogen storage inside graphene-oxide frameworks.
AB  - In this paper, we use applied mathematical modelling to investigate the storage
      of hydrogen molecules inside graphene-oxide frameworks, which comprise two
      parallel graphenes rigidly separated by perpendicular ligands. Hydrogen uptake is
      calculated for graphene-oxide frameworks using the continuous approximation and
      an equation of state for both the bulk and adsorption gas phases. We first
      validate our approach by obtaining results for two parallel graphene sheets. This
      result agrees well with an existing theoretical result, namely 1.85 wt% from our
      calculations, and 2 wt% arising from an ab initio and grand canonical Monte Carlo
      calculation. This provides confidence to the determination of the hydrogen uptake
      for the four graphene-oxide frameworks, GOF-120, GOF-66, GOF-28 and GOF-6, and we
      obtain 1.68, 2, 6.33 and 0 wt%, respectively. The high value obtained for GOF-28
      may be partly explained by the fact that the benzenediboronic acid pillars
      between graphene sheets not only provide mechanical support and porous spaces for
      the molecular structure but also provide the higher binding energy to enhance the
      hydrogen storage inside graphene-oxide frameworks. For the other three
      structures, this binding energy is not as large in comparison to that of GOF-28
      and this effect diminishes as the ligand density decreases. In the absence of
      conflicting data, the present work indicates GOF-28 as a likely contender for
      practical hydrogen storage.

PMID- 21719968
TI  - Tailoring the crystal structure of individual silicon nanowires by polarized
      laser annealing.
AB  - We study the effect of polarized laser annealing on the crystalline structure of
      individual crystalline-amorphous core-shell silicon nanowires (NWs) using Raman
      spectroscopy. The crystalline fraction of the annealed spot increases
      dramatically from 0 to 0.93 with increasing incident laser power. We observe
      Raman lineshape narrowing and frequency hardening upon laser annealing due to the
      growth of the crystalline core, which is confirmed by high resolution
      transmission electron microscopy (HRTEM). The anti-Stokes:Stokes Raman intensity
      ratio is used to determine the local heating temperature caused by the intense
      focused laser, which exhibits a strong polarization dependence in Si NWs. The
      most efficient annealing occurs when the laser polarization is aligned along the
      axis of the NWs, which results in an amorphous-crystalline interface less than
      0.5 um in length. This paper demonstrates a new approach to control the crystal
      structure of NWs on the sub-micron length scale.

PMID- 21719969
TI  - Direct growth of tellurium nanorod arrays on Pt/FTO/glass through a surfactant
      assisted chemical reduction.
AB  - Uniform tellurium nanorod arrays (TNA) have been successfully deposited directly
      on Pt/FTO (F-doped SnO(2))/glass substrate through a facile surfactant-assisted
      approach, which involved chemical reduction of TeO(3)(2-) ions by hydrazine
      hydrate. The whole synthesis process is highly repeatable and performed simply by
      immersing the Pt/FTO/glass in the solution for a certain time. During the growth
      of TNA, Pt catalyzed the reduction of TeO(3)(2-) ions by hydrazine hydrate and Te
      nanoparticles were deposited firmly on the substrate at first. Then, under the
      regulation of the surfactant (cetyltrimethylammonium bromide, CTAB), the
      deposited Te grew into nanorod arrays and adhered firmly to the substrate.
      Similar Te nanorod arrays could also grow on a Pd substrate which has the same
      catalytic performance as that of Pt. The as-synthesized TNA could be used as a
      good template to synthesize platinum-and gold-coated nanorods through convenient
      galvanic replacement. As a demonstration of potential application, the
      gold/tellurium nanorods showed uniform surface-enhanced Raman scattering (SERS)
      using rhodamine 6G (Rh6G) as the analyte. This approach provides a simple route
      for the growth of standing Te nanorods on a substrate, which may be used for the
      synthesis of other standing one-dimensional materials through a similar
      mechanism.

PMID- 21719970
TI  - Creating gold nanoprisms directly on quartz crystal microbalance electrodes for
      mercury vapor sensing.
AB  - A novel electrochemical route is used to form highly {111}-oriented and size
      controlled Au nanoprisms directly onto the electrodes of quartz crystal
      microbalances (QCMs) which are subsequently used as mercury vapor sensors. The Au
      nanoprism loaded QCM sensors exhibited excellent response-concentration linearity
      with a response enhancement of up to ~ 800% over a non-modified sensor at an
      operating temperature of 28  degrees C. The increased surface area and atomic
      scale features (step/defect sites) introduced during the growth of nanoprisms are
      thought to play a significant role in enhancing the sensing properties of the Au
      nanoprisms toward Hg vapor. The sensors are shown to have excellent Hg sensing
      capabilities in the concentration range of 0.123-1.27 ppm(v) (1.02-10.55 mg m(
      3)), with a detection limit of 2.4 ppb(v) (0.02 mg m(-3)) toward Hg vapor when
      operating at 28  degrees C, and 17 ppb(v) (0.15 mg m(-3)) at 89  degrees C,
      making them potentially useful for air monitoring applications or for monitoring
      the efficiency of Hg emission control systems in industries such as mining and
      waste incineration. The developed sensors exhibited excellent reversible behavior
      (sensor recovery) within 1 h periods, and crucially were also observed to have
      high selectivity toward Hg vapor in the presence of ethanol, ammonia and
      humidity, and excellent long-term stability over a 33 day operating period.

PMID- 21719971
TI  - Nanosilicon in water as a source of hydrogen: size and pH matter.
AB  - We report on the interaction of silicon nanocrystals with water/alcohol solutions
      which results in their complete oxidation, the hydrolysis of water and hydrogen
      generation in amounts close to the ideal scenario. Water acts as an oxidizer
      while alcohol is required for efficient wetting of nanosilicon. This process
      results in the formation of silicon-based alcogel which can be further
      transferred to aerogel.

PMID- 21719972
TI  - Electrostatic interaction forces in aqueous salt solutions of variable
      concentration and valency.
AB  - We use atomic force microscopy (AFM) to determine electrostatic interactions
      between Si tips and Si wafers in aqueous electrolytes of variable composition. We
      demonstrate that dynamic force spectroscopy (DFS) in the frequency modulation
      (FM) mode with stiff cantilevers and sharp tips allows for a continuous detection
      of the tip-sample interactions without mechanical jump-to-contact instability and
      with substantially higher lateral resolution than standard colloidal probe
      measurements. For four different species of salt (NaCl, KCl, MgCl(2), CaCl(2)) we
      find repulsive electrostatic forces at the lowest salt concentrations (1 mM) that
      become progressively screened until they are dominated by attractive van der
      Waals forces at the highest concentration (100 mM). For the divalent cations the
      crossover from repulsive to attractive forces occurs at lower concentrations than
      for monovalent cations. Surface charges extracted from fits to standard Poisson
      Boltzmann double layer theory indicate a rather weak dependence of the surface
      charge on the ion concentration. The high lateral resolution of our approach is
      illustrated by a 2D force field measurement over a patterned surface of a
      supported lipid bilayer on a mica substrate.

PMID- 21719973
TI  - In situ observations of endotaxial growth of CoSi2 nanowires on Si(110) using
      ultrahigh vacuum transmission electron microscopy.
AB  - We report in situ observations of the growth of endotaxial CoSi(2) nanowires on
      Si(110) using an ultrahigh vacuum transmission electron microscope with a
      miniature electron-beam deposition system located above the pole-piece of the
      objective lens. Metal deposition at 750-850  degrees C results in formation of
      coherently strained silicide nanowires with a fixed length/width (L/W) aspect
      ratio that depends strongly on temperature. Both dimensions evolve with time as
      L, W ~ t(1/3). To explain this behavior, we propose a fixed-shape growth mode
      based on thermally activated facet-dependent reactions. A second growth mode is
      also observed at 850  degrees C, with dimensions that evolve as L ~ t and W ~
      constant. This mode is accompanied by formation of an array of dislocations. We
      expect that other endotaxial nanowire systems will follow coherently strained
      growth modes with similar geometrical constraints, as well as dislocated growth
      modes with different growth kinetics.

PMID- 21719974
TI  - Auxiliary drying to prevent pattern collapse in high aspect ratio nanostructures.
AB  - Many defects are generated in densely packed high aspect ratio structures during
      nanofabrication. Pattern collapse is one of the serious problems that may arise,
      mainly due to the capillary force during drying after the rinsing process. In
      this paper, a method of auxiliary drying is presented to prevent pattern collapse
      in high aspect ratio nanostructures by adding an auxiliary substrate as a
      reinforcing rib to restrict deformation and to balance the capillary force. The
      principle of the method is presented based on the analysis of pattern collapse. A
      finite element method is then applied to analyze the deformation of the resist
      beams caused by the surface tension using the ANSYS software, and the effect of
      the nanostructure's length to width ratio simulated and analyzed. Finally, the
      possible range of applications based on the proposed method is discussed. Our
      results show that the aspect ratio may be increased 2.6 times without pattern
      collapse; furthermore, this method can be widely used in the removal of solvents
      in micro- and nanofabrication.

PMID- 21719975
TI  - Structure, morphology and magnetic properties of Mg((x))Zn((1 - x))Fe2O4 ferrites
      prepared by polyol and aqueous co-precipitation methods: a low-toxicity
      alternative to Ni((x))Zn((1 - x))Fe2O4 ferrites.
AB  - The synthesis and properties of Mg((x))Zn((1 - x))Fe(2)O(4) spinel ferrites as a
      low-toxicity alternative to the technologically significant Ni((x))Zn((1 -
      x))Fe(2)O(4) ferrites are reported. Ferrite nanoparticles have been formed
      through both the polyol and aqueous co-precipitation methods that can be readily
      adapted to industrial scale synthesis to satisfy the demand of a variety of
      commercial applications. The structure, morphology and magnetic properties of
      Mg((x))Zn((1 - x))Fe(2)O(4) were studied as a function of composition and
      particle size. Scanning electron microscopy images show particles synthesised by
      the aqueous co-precipitation method possess a broad size distribution (i.e. ~ 80
      120 nm) with an average diameter of the order of 100 nm +/- 20 nm and could be
      produced in high process yields of up to 25 g l(-1). In contrast, particles
      synthesised by the polyol-based co-precipitation method possess a narrower size
      distribution with an average diameter in the 30 nm +/- 5 nm range but are limited
      to smaller yields of ~ 6 g l(-1). Furthermore, the polyol synthesis method was
      shown to control average particle size by varying the length of the glycol
      surfactant chain. Particles prepared by both methods are compared with respect to
      their phase purity, crystal structure, morphology, magnetic properties and
      microwave properties.

PMID- 21719976
TI  - [Assessment of vertebral fractures on radiographs and the effects of drug therapy
      on vertebral fractures].
AB  - Vertebral radiographs remain the best method for assessing the presence of
      vertebral fractures. Both quantitative morphometric (QM) and semiquantitative
      morphometric (SQ) techniques are using for the assessment of prevalent as well as
      incident vertebral fractures on radiographs. Recently, SQ method has been mainly
      used for clinical study. A prevalent fracture is defined as a vertebral body with
      a SQ grade of 1 or more, and an incident fracture is defined as an increase of at
      least 1 grade in a vertebral body. Randomized placebo-controlled double- blind
      studies indicated that usable drugs in Japan, for example, oral amino-
      bisphophonates, SERMs, and teriparatide significantly reduced the risk of
      vertebral fracture, and relative risk reduction were 30 to 65%.

PMID- 21719977
TI  - [Early diagnosis and staging of rheumatoid arthritis by MR imaging and
      ultrasonography].
AB  - Advanced imaging modalities, such as MR imaging or ultrasonography (US), are
      useful in evaluating disease activity and therapeutic outcome of rheumatoid
      arthritis (RA). MR imaging can demonstrate bone erosion and edema, which are
      important in predicting structural articular damage. MR findings are nonspecific
      but can be helpful in diagnosing RA in its early stage. US can access relatively
      easily to multiple joints, and power Doppler US allows to visualize the
      vascularity of synovium. Standardization of imaging and analysis procedures are
      needed for clinical application of these imaging modalities.

PMID- 21719978
TI  - [Image assessment of the cartilage and subchondral bone in patients with
      osteoarthritis].
AB  - The most recommendable MRI sequence for the morphologic assessment of the
      cartilage damage due to osteoarthritis (OA) is gradient echo fat suppression T1
      weighted image (SPGR: Spoiled gradient recalled acquisition in the steady state,
      FLASH: Fast low-angle shot). For the detection of the cartilage degeneration
      before the morphological change, T2 mapping, dGEMRIC (delayed Gd-DTPA2-Enhanced
      MRI of Cartilage), and T1rho mapping are suggested. Subchondral bone structural
      changes such as bone sclerosis and cyst are deeply related to the etiology of OA,
      and quantitative evaluation for them using MDCT (Multi-Detector row CT) and 3TMRI
      are suggested.

PMID- 21719979
TI  - [Imaging appearances of subchondral insufficiency fracture].
AB  - A subchondral insufficiency fracture of the femoral head (SIF) is a recently
      proposed concept, which has generally been observed in elderly women with
      osteoporosis as well as in patients who have undergone a renal transplantation.
      In addition, this fracture is sometimes seen in young adults. Some cases of
      subchondral insufficiency fracture were managed by non-operative treatment, while
      others demonstrated disease progression until bone collapse which necessitated
      surgery. The low intensity band on the T1-weighted magnetic resonance images has
      been reported to be one of the characteristic imaging appearances in SIF, which
      corresponds histologically to the fracture line and associated fracture repair
      tissue. Therefore, the shape of the low intensity band generally tends to be
      irregular, disconnected, and convex to the articular surface. This finding has
      been considered to be useful for the differentiation with osteonecrosis.

PMID- 21719980
TI  - [Assessment of volumetric bone mineral density and geometry for hip with clinical
      CT device].
AB  - It is one of the most important challenges for preventing hip fractures to
      establish an accurate non-invasive assessment of hip fracture risk. Quantitative
      computed tomography (QCT) is able to analyze not only volumetric bone mineral
      density (mg/cm3) of trabecular and cortical bone compartment separately, but also
      geometry and biomechanical parameters in bone such as cross-sectional area,
      cortical bone thickness, section modulus, buckling ratio etc. The analysis of
      geometry and biomechanical parameters at hip could provide better prediction of
      hip fracture risk, better understanding pathogenesis of hip fractures, and thus
      better selection of drug and/or lifestyle-based interventions.

PMID- 21719981
TI  - In vivo assessment of trabecular and cortical bone microstructure.
AB  - In addition to bone mineral density (BMD), bone microstructure is a major
      contributor to bone strength. With recently developed technologies we are able to
      assess bone microstructure in vivo . These technologies include high-resolution
      peripheral quantitative computed tomography (HR-pQCT), multi-detector computer
      tomography (MDCT), and high-resolution magnetic resonance imaging (HR-MRI). Using
      HR-pQCT both cortical and trabecular microstructure can be assessed with a voxel
      size of 82MUm. While MDCT and HR-MRI have lower spatial resolution than HR-pQCT,
      they have the main advantage of imaging central sites such as the proximal femur.
      Using these technologies a variety of parameters can be measured including bone
      volume ratio, trabecular thickness and number, cortical thickness, and cortical
      porosity. In vivo microstructure measurements are associated with fracture risk
      and these measurements can be combined with finite element modeling to estimate
      bone strength. While limitations exist, such as measurement of only peripheral
      sites and motion artifacts, the assessment of microstructure is promising and
      provides clinically relevant information. The techniques may help to better
      predict fracture risk and determine the efficacy of treatments for metabolic bone
      diseases.

PMID- 21719982
TI  - [Prediction of bone strength using a quantitative computed tomography based
      finite element method].
AB  - Clinically available methods for estimating bone strength include bone
      densitometry techniques such as dual energy X-ray absorptiometry and quantitative
      computed tomography, and other diagnostic imaging procedures such as radiographic
      imaging. These techniques evaluate regional bone density and morphology, which
      are partly related to fracture risk, but are of limited value for quantifying
      structural strength. Therefore, it is necessary to develop a noninvasive method
      for accurate quantitative structural analysis that incorporates information on
      both morphology and bone density in a three-dimensional distribution. Computed
      tomography-based finite element method (CT/FEM), which incorporates information
      on both the three-dimensional architecture and bone density distribution, could
      possibly achieve precise assessment of the strength of the bone. We focused on a
      CT/FEM to quantify structural strength, developing a nonlinear CT/FEM to achieve
      accurate assessment of strength in the proximal femur and lumbar vertebrae. Here,
      we describe the CT/FEM.

PMID- 21719983
TI  - [Bone researches using synchrotron radiation].
AB  - Bone researches with synchrotron radiation have now expanded from a simple
      mineralization measurement to more complicated studies such as strain mapping and
      tissue engineering. The most common techniques are high resolution X-ray
      tomography and X-ray diffraction, but the spectroscopic techniques such as
      fluorescence analysis, infrared FTIR and XAFS are also available. High resolution
      X-ray tomography has been improved in the time and spatial resolution. In vitro
      tomographic experiments have become common and been applied to 3D imaging of a
      live mouse. As a new imaging method, coherent diffraction imaging has been
      applied to visualize the lacunocanalicular network. As each of these techniques
      provides unique information and the sample condition depends much on the
      technique, the choice of the technique is important to achieve a scientific goal.

PMID- 21719984
TI  - [Bone analysis by in vivo optical imaging].
AB  - There has been a growing interest in analyzing complex biology in living animals
      by in vivo fluorescent imaging. In vivo fluorescent imaging by using novel
      fluorescent molecular probes and advanced fluorescent microscopy e.g. two-photon
      microscopy allow us to analyze deep tissues in bone. In this review, we
      demonstrated our data and discussed about in vivo fluorescent imaging in bone
      research field.

PMID- 21719985
TI  - [Image assessment of the treatment effect on osteoporosis: bisphosphonates].
AB  - Bisphosphonates are potent antiresorptive agents and are widely used to treat
      osteoporosis. They reduce the incidence of new fractures by increasing BMD, which
      partly reflects an increase in the degree of mineralization, and by preventing
      the deterioration of bone microarchitecture. Iliac crest bone biopsies have shown
      the improvement of bone architecture after bisphosphonate treatment. Recently,
      high resolution CT and dual X-ray absorptiometry have also been applied to
      evaluate the architectural change in bisphosphonate treatment.

PMID- 21719986
TI  - [Diagnostic imaging of treatment in osteoporosis: SERM].
AB  - The effectiveness of selective estrogen receptor modulator (SERM) in X-ray, dual
      X-ray Absorptiometry (DXA), quantitative computed tomography (QCT), and hip
      structure analysis (HSA) are reviewed. Raloxifene and bazedoxifene increase bone
      mineral density in the spine and femoral neck, and reduce risk of vertebral
      fracture in women with osteoporosis, and reduce risk of nonvertebral fractures in
      women with higher fracture risk. Raloxifene improved bone density and micro
      architecture in spine and limbs (distal radius and distal tibia) represented by
      volumetric QCT and high-resolution peripheral QCT. Raloxifene also improved HSA
      parameters in femoral neck, intertrochanter, and shaft regions. The tendency to
      change in these parameters is approximately similar in raloxifene and
      bisphosphonates (alendronate, risedronate, minodronate). These results indicate
      that raloxifene improved the bone density and bone quality in spine, limbs and
      hip.

PMID- 21719987
TI  - [Diagnostic imaging of treatment in osteoporosis; new active vitamin D].
AB  - Active vitamin D drugs, such as alfacalcidol or calcitriol, have been on the
      market for about 30 years as a remedy for osteoporosis and are still the most
      popular drugs for osteoporosis in Japan. Eldecalcitol (EDR), a new active vitamin
      D compound, became the production sale approval in 2011. The results of the
      randomized, active comparator, double blind study to compare its anti-fracture
      efficacy with alfacalcidol (ALF) concluded that EDR has superior effect to ALF in
      preventing vertebral fractures in osteoporotic patients. Moreover, our
      longitudinal analysis of hip geometry by clinical CT in a subgroup has disclosed
      an unexpected potential of EDR to increase the cortical cross-sectional area and
      to maintain cortical thickness, probably through a more potent effect of EDR in
      mitigating endocortical bone resorption compared to ALF.

PMID- 21719988
TI  - [Diagnostic imaging of treatment in osteoporosis: PTH].
AB  - Parathyroid hormone (PTH [1-34]) stimulates bone formation and activates bone
      remodeling, resulting in increase of bone mass and strength. The effect on bone
      quality appears through the different mechanism from the anti-resorptive agents.
      The anti-resorptive agent maintains the trabecular microstructure, decreases the
      cortical porosity and increases the degree of mineralization, meanwhile, the
      anabolic agent such as PTH increases trabecular number and cortical thickness,
      decreases the mineralization and increases cortical porosity. Both different
      mechanisms of anti-resorptive and anabolic agents improve the biomechanical
      properties of bone. Micro-CT and clinical CT images demonstrate the effect of PTH
      on bone quality.

PMID- 21719989
TI  - Application of the new logistic model to microbial growth prediction in food.
AB  - Recently a microbial growth model, the new logistic model, which could precisely
      describe and predict microbial growth at various patterns of temperature, was
      developed by the author (Biocontrol Science, 15, 75-80, 2010). The author shows
      several software programs developed with the model in this review. First, a
      program that analyzes microbial growth data and generates growth curves fitted to
      the model was developed. Second, a growth prediction program for Escherichia
      coli, Staphylococcus aureus, and Vibrio paraheamolyticus [corrected] exposed at
      various patterns of temperature was made based on experimental data. For V.
      paraheamolyticus [corrected] a program for bacterial growth under environmental
      conditions including temperature, salt concentration, and pH was developed. These
      programs are available free at the Japan Food Industry Center. Furthermore, a
      method to estimate the temperature at various points on or inside a food exposed
      to a given temperature was developed by using the measured temperatures of two
      points on the surface of the food and the heat conduction law. Combining this
      method with the growth model, a system that predicts microbial growth in a food
      exposed to various temperature patterns was made. This system could be a
      prototype of an alert system for microbial food safety.

PMID- 21719990
TI  - Cloning and analysis of the ggpS gene from Cyanobacteria Arthrospira spp.
      involved in the synthesis of an osmolyte glucosylglycerol.
AB  - The genus Arthrospira is a nonheterocystous filamentous cyanobacterium inhabiting
      diverse environments including those of high salinity. In the present study,
      Arthrospira strains were isolated from freshwater and brackish lakes in Myanmar,
      and their osmoprotective adaptation was investigated as it was for the genus
      Synechococcus strains. The Arthrospira strains showed satisfactory growth up to
      1.0 M sodium chloride, suggesting their acclimation to high salinity stress.
      Cloning and phylogenetic analysis of ggpS, which encodes an osmolyte
      glucosylglycerol-phosphate synthase (GgpS), showed that the cyanobacterial
      strains possess a GgpS-based osmoprotective mechanism, except for Synechococcus
      strains of freshwater origin. The Arthrospira spp. strains fell into the same
      cluster in the GgpS phylogeny, suggesting their close taxonomic relationship. One
      exception was Arthrospira sp. TT-1 (II); the ggpS (II), possibly a paralogue of
      the ggpS (I), branched out from the cyanobacterial cluster. These findings
      suggest the wide distribution of the genus Arthrospira in freshwater to brackish
      environments is ascribed to its glucosylglycerol production as an osmoprotectant
      and resulting in salt acclimation.

PMID- 21719991
TI  - Inhibitory effects on microbial growth using the derivatives of benzyl phenyl
      sulfide.
AB  - We investigated the antimicrobial activities of twelve derivatives of benzyl
      phenyl sulfide by using Minimum Inhibitory Concentration (MIC) and Minimum
      Bactericidal Concentration (MBC) values against 10 microbial strains. These
      derivatives of benzyl phenyl sulfides were synthesized by means of the
      nucleophilic coupling reaction at our laboratory. MIC testing revealed that all
      synthetic derivatives of benzyl and 4-methoxybenzyl phenyl sulfides had no effect
      against the tested microbial strains. However, the compounds of 4-nitrobenzyl
      phenyl sulfide showed antimicrobial activity against many of the tested strains.
      Above all, 4-nitrobenzyl 4-chlorophenyl sulfide 11 exhibited the strongest and
      widest ranging inhibitory effects among the twelve synthetic compounds. We
      researched the antimicrobial activities of the coupling materials of sulfide. As
      a result, it was considered important for the expression of antimicrobial
      activities that the sulfide had a 4-nitrobenzyl group and 4-chlorophenyl group in
      the same molecule as in the case of benzyl phenyl sulfide.

PMID- 21719992
TI  - Roles of multidrug efflux pumps on the biofilm formation of Escherichia coli K
      12.
AB  - We genetically analyzed the roles of multidrug efflux pumps on the biofilm
      formation of Escherichia coli K-12 BW25113. We used 22 mutants missing various
      genes related to the multidrug efflux pumps and found that the biofilm formation
      of emrD, emrE, emrK, acrD, acre and mdtE-deleted mutants was extremely decreased.
      These results indicate that some multidrug efflux pumps significantly contribute
      to the biofilm formation of E. coli.

PMID- 21719993
TI  - Compact Dry(R) X-BC for the enumeration of Bacillus cereus in food samples.
AB  - We evaluated the effectiveness of using Compact Dry(R) X-BC (CD-XBC), a ready-to
      use and self-diffusing dry medium sheet culture system based on a novel detection
      principle, for the detection and enumeration of Bacillus cereus. All 13 B. cereus
      strains, which were studied for the inclusivity study, grew as blue/green
      colonies on the CD-XBC. When 3 yeast strains and 103 bacterial strains other than
      B. cereus were tested for the exclusivity study, 5 strains formed white colonies,
      and 4 strains formed blue/green colonies, while 94 other strains failed to grow.
      The 4 strains that formed blue/green colonies were B. thuringiensis, which is
      known to have the same biochemical features as B. cereus. The CD-XBC method was
      compared with the MYP agar method (MYP) and the NGKG agar method (NGKG) in 130
      artificially contaminated food samples. The correlation coefficients between CD
      XBC and MYP, and CD-XBC and NGKG were 0.972 and 0.971, respectively.

PMID- 21719994
TI  - Decontamination effect of milling by a jet mill on bacteria in rice flour.
AB  - The decontamination effect of milling by a jet mill was investigated by counting
      the number of bacteria in brown and white rice flour with mean particle diameters
      of 3, 20, and 40um prepared by the jet mill. In the jet mill, the particles are
      crushed and reduced in size by the mechanical impact caused by their collision.
      Although the brown and white rice grains were contaminated with approximately
      10(6) and 10(5) CFU/g bacteria, the microbial load of the rice flour decreased as
      the mean particle diameter decreased, ultimately decreasing to approximately 104
      and 103 CFU/g in the brown and white rice flour. The temperature and pressure
      changes of the sample were not considered to have an effect on reducing the
      bacterial count during the milling. Hence, it was thought that the rice flour was
      decontaminated by other effects.

PMID- 21719995
TI  - Exploration of new molecular mechanisms for antidepressant actions of
      electroconvulsive seizure.
AB  - Electroconvulsive seizure (ECS) therapy is a clinically proven treatment for
      depression and is often effective even in patients resistant to chemical
      antidepressants. However, the molecular mechanisms underlying the therapeutic
      efficacy of ECS are not fully understood. Here, I review studies that show
      molecular, cellular, and behavioral changes by ECS treatment, and discuss the
      functions of ECS to underlie the action of antidepressant effects. In
      hippocampus, these changes cover gene induction, increased adult neurogenesis,
      and electrophysiological reactivity. Especially, the role of vascular endothelial
      growth factor (VEGF) in neurogenesis is discussed. Among other gene expression
      changes in hippocampus, a role of cyclooxygenase (COX)-2, an inducible type of
      the rate-limiting enzyme of prostanoid synthesis, is focused. ECS-induced changes
      in other brain regions such as prefrontal cortex and hypothalamus, and ECS
      induced behavioral changes are also reviewed. Understanding the molecular,
      cellular, and behavioral changes by ECS will provide a new view to find potential
      targets for novel antidepressant design that are highlighted by these findings.

PMID- 21719996
TI  - Niosomes: a controlled and novel drug delivery system.
AB  - During the past decade formulation of vesicles as a tool to improve drug
      delivery, has created a lot of interest amongst the scientist working in the area
      of drug delivery systems. Vesicular system such as liposomes, niosomes,
      transferosomes, pharmacosomes and ethosomes provide an alternative to improve the
      drug delivery. Niosomes play an important role owing to their nonionic
      properties, in such drug delivery system. Design and development of novel drug
      delivery system (NDDS) has two prerequisites. First, it should deliver the drug
      in accordance with a predetermined rate and second it should release
      therapeutically effective amount of drug at the site of action. Conventional
      dosage forms are unable to meet these requisites. Niosomes are essentially non
      ionic surfactant based multilamellar or unilamellar vesicles in which an aqueous
      solution of solute is entirely enclosed by a membrane resulting from the
      organization of surfactant macromolecules as bilayer. Niosomes are formed on
      hydration of non-ionic surfactant film which eventually hydrates imbibing or
      encapsulating the hydrating aqueous solution. The main aim of development of
      niosomes is to control the release of drug in a sustained way, modification of
      distribution profile of drug and for targeting the drug to the specific body
      site. This paper deals with composition, characterization/evaluation, merits,
      demerits and applications of niosomes.

PMID- 21719997
TI  - Inositol 1,4,5-trisphosphate receptor-mediated initial Ca(2+) mobilization
      constitutes a triggering signal for hydrogen peroxide-induced apoptosis in INS-1
      beta-cells.
AB  - Reactive oxygen species, including hydrogen peroxide (H(2)O(2)), are known to
      induce beta-cell apoptosis. The present study investigated the role of Ca(2+) in
      H(2)O(2)-induced apoptosis of the beta-cell line INS-1. Annexin V assay with flow
      cytometry and DNA ladder assay demonstrated that treatment of INS-1 cells with
      100 uM H(2)O(2) for 18 h significantly increased apoptotic cells. A comparable
      level of apoptosis was also observed after 18 h when the cells were treated with
      100 uM H(2)O(2) only for initial 30 min. The H(2)O(2)-induced apoptosis was
      abolished by 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      tetra(acetoxymethyl)ester (BAPTA/AM), a chelator of intracellular Ca(2+), by 2
      aminoethoxydiphenylborate (2-APB), a blocker of inositol 1,4,5-trisphosphate
      (IP(3)) receptors and cation channels, and by xestospongin D, a blocker of IP(3)
      receptors, and was partially blocked by SKF-96365, a non-selective cation channel
      blocker. However, nicardipine, an L-type voltage-dependent Ca(2+) channel
      blocker, or N-(p-amylcinnamoyl)anthranilic acid (ACA), a TRPM2 blocker, had
      little effect on the apoptosis. The inhibitory effect of BAPTA/AM or 2-APB on the
      H(2)O(2)-induced apoptosis was largely attenuated when the drug was added 30 min
      or 1 h after start of the treatment with H(2)O(2). These results suggest that the
      initial intracellular Ca(2+) elevation induced by H(2)O(2), which is mediated via
      IP(3) receptors and store-operated cation channels, plays an obligatory role in
      the induction of beta-cell apoptosis.

PMID- 21719998
TI  - Cornuside suppresses lipopolysaccharide-induced inflammatory mediators by
      inhibiting nuclear factor-kappa B activation in RAW 264.7 macrophages.
AB  - Cornuside, a secoiridoid glucoside compound, was isolated from the fruit of
      Cornus officinalis SIEB. et ZUCC. Cornuside has been reported to possess
      immunomodulatory and anti-inflammatory activities. However, the effects and
      mechanism of action of cornuside in inflammation have not been fully
      characterized. The present study was therefore designed to examine whether
      cornuside suppresses inflammatory response in lipopolysaccharide (LPS)-stimulated
      RAW 264.7 macrophage cells. Cornuside significantly inhibited the LPS-induced
      production of nitric oxide, prostaglandin E(2), tumor necrosis factor-alpha,
      interleukin-6 (IL-6), and IL-1beta. The mRNA and protein expressions of inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also decreased by
      cornuside. Furthermore, cornuside significantly attenuated the LPS-stimulated
      phosphorylation and degradation of inhibitory kappa B-alpha and the subsequent
      translocation of the p65 subunit of nuclear factor-kappa B (NF-kappaB) to the
      nucleus. Cornuside also reduced the phosphorylations of extracellular-signal
      related kinase (ERK1/2), p38, and c-Jun N-terminal kinase (JNK1/2). These results
      suggest that the anti-inflammatory property of cornuside is related to the
      downregulations of iNOS and COX-2 due to NF-kappaB inhibition as well as the
      negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7
      cells.

PMID- 21719999
TI  - Bufalin inhibits platelet-derived growth factor-BB-induced mesangial cell
      proliferation through mediating cell cycle progression.
AB  - Bufalin, a traditional Chinese medicine, has been reported as a protective factor
      in many tumors. We therefore investigated the effect of bufalin on platelet
      derived growth factor (PDGF)-BB-induced proliferation of cultured rat mesangial
      cells. The effect of bufalin on cell proliferation and its underlying mechanisms
      were investigated in cultured rat mesangial cells (MCs) by the
      methylthiazoletetrazolium (MTT) assay, flow cytometry, reverse transcription
      polymerase chain reaction (RT-PCR), Western blotting, and cyclin-dependent
      kinases (CDK)2 and CDK4 kinase assays. Bufalin inhibited 20 ng/ml PDGF-BB-induced
      MC proliferation in a dose-dependent manner. Similar results were observed in
      different concentrations of bufalin, which blocked PDGF-BB-induced progression
      through G0/G1 to S phase of the cell cycle. Furthermore, bufalin not only
      inhibited upregulation of cyclin D1 and CDK4, but also downregulation of p21 in
      both mRNA and protein levels. Although bufalin did not affect p27 and CDK2 mRNA
      expression, it reversed downregulation of p27 and upregulation of CDK2 in protein
      level. Activity of CDK2 and CDK4 was also inhibited by bufalin. However, both
      bufalin and PDGF-BB did not affect cyclin E mRNA or protein expression. These
      results suggest that bufalin could inhibit MC proliferation by modulating cell
      cycle progress, indicating that bufalin could be a potential therapeutic agent
      for the prevention of mesangial proliferative glomerulonephritis.

PMID- 21720000
TI  - Curcumin ameliorates cardiac inflammation in rats with autoimmune myocarditis.
AB  - Curcumin is a natural polyphenolic compound abundant in the rhizome of the
      perennial herb turmeric, Curcuma longa. It is commonly used as a dietary spice
      and coloring agent in cooking, and is used anecdotally as an herb in traditional
      Indian and Chinese medicine. It has been reported that curcumin has the potential
      to protect against cardiac inflammation through suppression of GATA-4 and nuclear
      factor-kappaB (NF-kappaB); however, no study to date has addressed the effect of
      curcumin on experimental autoimmune myocarditis (EAM) in rats. In this study, 8
      week-old male Lewis rats were immunized with cardiac myosin to induce EAM. They
      were then divided randomly into a treatment or vehicle group and orally
      administrated curcumin (50 mg/kg/d) or 1% gum arabic, respectively, for 3 weeks
      after myosin injection. We performed hemodynamic, echocardiographic, hematoxylin
      and eosin staining, mast cell staining and Western blotting studies to evaluate
      the protective effect of curcumin in the acute phase of EAM. Cardiac functional
      parameters measured by hemodynamic and echocardiographic studies were
      significantly improved by curcumin treatment. Furthermore, curcumin reduced the
      heart weight-to-body weight ratio, area of inflammatory lesions and the
      myocardial protein level of NF-kappaB, interleukin (IL)-1beta, tumor necrosis
      factor (TNF)-alpha and GATA-4. Our results indicate that curcumin has the
      potential to protect against cardiac inflammation through suppression of IL
      1beta, TNF-alpha, GATA-4 and NF-kappaB expresses, and may provide a novel
      therapeutic strategy for autoimmune myocarditis.

PMID- 21720001
TI  - Activation of extracellular-signal regulated kinase by platelet-derived growth
      factor is potentiated by phenylephrine in primary cultures of adult rat
      hepatocytes.
AB  - We investigated the effects of the alpha(1)-adrenergic agonist phenylephrine on
      platelet-derived growth factor (PDGF)-stimulated extracellular signal-regulated
      kinase (ERK) in primary cultures of adult rat hepatocytes. Hepatocytes were
      isolated and cultured with PDGF (10 ng/ml) and/or alpha-adrenergic agonist.
      Phosphorylated ERK isoforms (ERK1 and ERK2) were detected by Western blotting
      analysis using anti-phospho mitogen-activated protein kinase (MAPK) antibody.
      PDGF stimulated phosphorylation of ERK2 (42 kDa MAPK) by 2.0-fold within 3-5 min.
      The PDGF-induced ERK activation was abolished by AG1296 (10(-7) M) or LY294002
      (10(-7) M) treatment. MAPK kinase inhibitor, PD98059 (10(-6) M), completely
      inhibited the PDGF-induced increase in ERK activity. In addition, PDGF-induced
      mammalian target of rapamycin activity was completely inhibited by AG1296,
      LY294002, PD98059, or rapamycin treatment. Phenylephrine alone showed no effects
      on ERKs, but significantly increased phosphorylation of ERK2 induced by PDGF.
      Moreover, a synthetic analog of diacylglycerol (DG), phorbol 12-myristate 13
      acetate (TPA; 10(-7) M), potentiated PDGF-induced ERK2 phosphorylation, while
      ionomycin had no effect (10(-6) M). The effects of phenylephrine and TPA were
      antagonized by the phospholipase C (PLC) inhibitor U73122 (10(-7) M), and the
      protein kinase C (PKC) inhibitor GF109203X (10(-7) M), respectively. Accordingly,
      PDGF-induced DNA synthesis and proliferation in the presence or absence of
      phenylephrine or TPA were completely inhibited by AG1296, LY294002, PD98059, or
      rapamycin treatment. These results suggest that activation of PLC/PKC by
      phenylephrine represent an indirect positive regulatory mechanism for stimulating
      ERK induced by 10 ng/ml PDGF.

PMID- 21720002
TI  - Stimulation of the proliferation and differentiation of skin cells by ferrous
      ferric chloride from a distance.
AB  - Ferrous ferric chloride (FFC) is a distinct form of aqueous iron composed of a
      complex of ferrous chloride and ferric chloride that participates in both
      oxidation and reduction reactions, and stimulates the proliferation and
      differentiation of mammalian keratinocytes, melanocytes, and fibroblasts.
      However, it is not known whether FFC can stimulate their proliferation and
      differentiation without being added into culture media or painted on the skin.
      This study aims to clarify whether FFC can stimulate their proliferation and
      differentiation from a distance without being added to culture media. In this
      study, FFC-containing skin lotions were painted under the culture dishes (1 mm
      away from cells) or on the top of the covers of 1 to 5 polystyrene culture dishes
      (1 to 5 cm away) and tested for their proliferation- and differentiation
      stimulating effects. FFC lotions stimulated the proliferation and differentiation
      of human keratinocytes, melanocytes, and fibroblasts from a distance of 1 mm to 1
      cm. However, FFC lotions failed to stimulate the proliferation and
      differentiation of melanocytes from distances of 2 to 5 cm. Results using Teflon
      covers were similar to those of polystyrene covers. Moreover, the effects of FFC
      lotions painted on the top of the Teflon covers were completely lost by lead
      disks. These results suggest that FFC can stimulate the proliferation and
      differentiation of skin cells from a distance of 1 cm without being added into
      culture media through physical factors rather than chemical factors.

PMID- 21720003
TI  - Plaque formation assay for human parainfluenza virus type 1.
AB  - Human parainfluenza virus type 1 (hPIV1) generally does not show visible plaques
      in common cell lines, including Lewis lung carcinoma-monkey kidney (LLC-MK(2))
      cells, by plaque formation assays for human parainfluenza virus type 3 (hPIV3)
      and Sendai virus. In several conditions of the plaque formation assay, complete
      elimination of serum proteins in the overlay medium was necessary for
      visualization of hPIV1-induced plaque formation in LLC-MK(2) cells. We developed
      a plaque formation assay for hPIV1 isolation and titration in LLC-MK(2) cells
      using an initial overlay medium of bovine serum albumin-free Eagle's minimum
      essential medium containing agarose and acetylated trypsin for 4-6 d followed by
      a second overlay staining medium containing agarose and neutral red. The assay
      allowed both laboratory and clinical hPIV1 strains to form large plaques. The
      plaque reduction assay was also performed with rabbit anti-hPIV1 antibody as a
      general evaluation model of viral inhibitors to decrease both the plaque number
      and size. The results indicate that the plaque formation assay is useful for
      hPIV1 isolation, titration, evaluation of antiviral reagents and epidemiologic
      research.

PMID- 21720004
TI  - Cladribine enhances apoptotic cell death in lung carcinoma cells over-expressing
      DNase gamma.
AB  - Worldwide, lung cancer is the most common form of cancer and often has a poor
      prognosis. Establishment of effective therapies for lung cancer is a major
      concern in clinical cancer research. We compared the cytotoxic effects of
      chemotherapeutic agents including cisplatin, 5-fluorouracil, vinorelbine and
      cladribine, on a human lung cancer cell line, A549, and its derivative
      transfected with the DNase gamma gene. We observed selective cytotoxicity of
      cladribine on the DNase gamma-expressing sub-cell line of A549. Cladribine
      induces selective apoptosis in DNase gamma-expressing A549 cells, which depends
      on activation of caspases. These results suggest that a combination therapy that
      includes cladribine along with the introduction of DNase gamma has potential as a
      new therapeutic strategy for lung cancer.

PMID- 21720005
TI  - Correlation between hyper-sensitivity to hydrogen peroxide and low defense
      against Ca(2+) influx in cataractogenic lens of Ihara cataract rats.
AB  - Our previous studies have demonstrated that lipid peroxidation in the lenses of
      hereditary cataract model rats (Ihara cataract rat (ICR)/f rats) caused a
      dysfunction in Ca(2+) regulation. In the present study, we investigated the
      effect of in vitro hydrogen peroxide (H(2)O(2)) stimulation on lipid peroxide
      (LPO) and the activities of sarco-/endoplasmic reticulum and plasma membrane
      Ca(2+)-ATPase (SERCA and PMCA) in the ICR/f rat lenses. An increase in LPO level
      and decreases in the SERCA and PMCA activities were observed with increasing
      H(2)O(2) concentration, and pretreatment with diethyldithiocarbamate, a potent
      radical scavenger, attenuated these changes in normal and ICR/f rat lenses. The
      glutathione levels, glutathione peroxidase and glutathione reductase activities
      are significantly lower in ICR/f rat lenses than in normal rat lenses.
      Furthermore, we presented as two kinetic parameters such as DP (defense point)
      and K(s) (reactive constant) analyzed from above various biological responses vs.
      H(2)O(2) concentration-profile curves using a one-exponential equation. The DPs
      for LPO, SERCA and PMCA in ICR/f rat lenses is lower than in normal rat lenses.
      In contrast to the results in DP, the K(s) for LPO, SERCA and PMCA in ICR/f rat
      lenses is higher than in normal rat lenses. In addition, the closed relationship
      of was observed between DP and K(s) for LPO, SERCA and PMCA. These results show
      that the resistance to H(2)O(2) in the ICR/f rat lenses is lower than that of
      normal rats. The DP and K(s) values can provide an useful information for
      resistances to various stimuli in cells and tissues.

PMID- 21720006
TI  - Evaluation of intestinal microbiotas of healthy Japanese adults and effect of
      antibiotics using the 16S ribosomal RNA gene based clone library method.
AB  - Intestinal microbiotas of human subjects and effect of antibiotic treatment on
      them have been reported with cultivation independent methods. However, Japanese
      fecal microbiotas have not been studied enough. We have constructed a clone
      library method to obtain results within 3 d. In this study, intestinal
      microbiotas of 29 healthy Japanese adults, whose fecal samples were collected
      twice at 5 month intervals from each subject, were analyzed with our clone
      library method, and using those data as a benchmark effect of antibiotic
      treatment on intestinal microbiotas was evaluated. The fifty-eight fecal
      microbiotas were assessed based on percentages at genus level, and the
      variability was analyzed with a principal component analysis (PCA). PCA showed
      that the microbiotas divided into three groups depending on the large
      eigenvectors (genera Ruminococcus, Bacteroides, and Prevotella), and the dual
      samples from the twenty-two individuals have belonged to the same PCA group. It
      suggests that almost Japanese adults have own stable intestinal microbiota. The
      genera Ruminococcus and Bacteroides were present in almost subjects, while the
      genus Prevotella was found only in nine subjects (approximately 30%) which was
      preserved with 5 months intervals. Next, the microbiotas before and after
      antibiotic treatment were evaluated comparing with the 58 healthy adult
      microbiotas. The results showed that beta-lactams influenced profoundly on
      intestinal microbiotas and the effect of macrolides depended on the cases. It
      suggests that our clone library method could show overview of intestinal
      microbiota and would give us useful information about the effect of antibiotic
      treatment for daily clinical diagnosis.

PMID- 21720007
TI  - Batatasin I, a naturally occurring phenanthrene derivative, isolated from
      tuberous roots of Dioscorea batatas suppresses eicosanoids generation and
      degranulation in bone marrow derived-mast cells.
AB  - To find anti-inflammatory compounds from the tuberous roots of Dioscorea batatas,
      we isolated 6-hydroxy-2,4,7-trimethoxyphenanthrene (batatasin I) from the
      dichloromethane (CH(2)Cl(2)) fraction of this plant. Batatasin I inhibited both
      the generation of prostaglandin D(2) (PGD(2)), leukotriene C(4) (LTC(4)) and
      degranulation reaction in mouse bone marrow-derived mast cells (BMMCs). This
      compound inhibited cyclooxygenase-2 (COX-2) dependent PGD(2) generation in a dose
      dependent manner, with IC(50) values of 1.78 uM. Western blotting probed with
      specific anti-COX-2 antibodies showed that the decrease in the quantity of the
      PGD(2) generation was accompanied by a decrease in the COX-2 protein level. In
      addition, this compound also inhibited the production of 5-lipoxygenase (5-LOX)
      dependent LTC(4) in a dose dependent manner (IC(50), 1.56 uM). Batatasin I also
      inhibited the mast cell degranulation reaction (IC(50), 6.7 uM) in BMMCs. This
      result indicates that batatasin I could be developed as an anti-inflammatory
      agent through further investigation.

PMID- 21720008
TI  - A prenylated flavan from Broussonetia kazinoki prevents cytokine-induced beta
      cell death through suppression of nuclear factor-kappaB activity.
AB  - The generation of nitric oxide (NO) via inducible NO synthase (iNOS) and reactive
      oxygen species plays a key role in cytokine-mediated pancreatic beta-cell damage.
      Oxidative stress due to reactive oxygen species activates the nuclear factor
      kappaB (NF-kappaB) transcription factor, which regulates iNOS expression. In this
      regard, suppression of the NF-kappaB pathway is a novel strategy for protecting
      beta-cells from damage. This study was performed to explore the effects of
      kazinol U, a prenylated flavan from Broussonetia kazinoki, on the NF-kappaB
      activation pathway in interleukin-1beta (IL-1beta)- and interferon-gamma (IFN
      gamma)-treated beta-cells. The cytotoxic effects of cytokines were completely
      abolished when RINm5F cells or islets were pretreated with kazinol U. Kazinol U
      inhibited the nuclear translocation and DNA binding of NF-kappaB subunits, which
      correlated with the inhibitory effects on IkappaB kinase (IKK) phosphorylation
      and IkappaBalpha degradation. In addition, kazinol U suppressed NO and hydrogen
      peroxide production and apoptotic cell death by cytokines in RINm5F cells. The
      protective effects of kazinol U were further demonstrated by normal insulin
      secretion of cytokine-treated islets in response to glucose. Taken together,
      these results suggest that using kazinol U to block the NF-kappaB pathway in
      pancreatic beta-cells reduces cell damage. Therefore, kazinol U may have
      therapeutic value in delaying pancreatic beta-cell destruction in type 1
      diabetes.

PMID- 21720009
TI  - Luteolin-7-O-glucoside suppresses leukotriene C(4) production and degranulation
      by inhibiting the phosphorylation of mitogen activated protein kinases and
      phospholipase Cgamma1 in activated mouse bone marrow-derived mast cells.
AB  - In this study, luteolin-7-O-glucoside (L7G), an herbal medicine isolated from
      Ailanthus altissima, inhibited 5-lipoxygenase (5-LOX)-dependent leukotriene C(4)
      (LTC(4)) production in bone marrow-derived mast cells (BMMCs) in a concentration
      dependent manner with an IC(50) of 3.0 uM. To determine the action mechanism of
      L7G, we performed immunoblotting for cytosolic phospholipase A(2) (cPLA(2)) and
      mitogen-activated protein kinases (MAPKs) following c-kit ligand (KL)-induced
      activation of BMMCs with or without L7G. Inhibition of LTC(4) production by L7G
      was accompanied by a decrease in cPLA(2) phosphorylation, which occurred via the
      extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 and c-Jun N
      terminal kinase (JNK) pathways. In addition, L7G also attenuated mast cell
      degranulation in a dose-dependent manner (IC(50), 22.8 uM) through inhibition of
      phospholipase Cgamma1 (PLCgamma1) phosphorylation. Our results suggest that the
      anti-asthmatic activity of L7G may be mediated in part via the inhibition of
      LTC(4) generation and mast cell degranulation.

PMID- 21720010
TI  - Dedifferentiation of human terminally differentiating keratinocytes into their
      precursor cells induced by basic fibroblast growth factor.
AB  - Reprogramming differentiated cells toward stem cells may have long-term
      applications in stem-cell research and regenerative medicine. Here we report on
      the dedifferentiation of human epidermal keratinocytes into their precursor cells
      in vitro with basic fibroblast growth factor (bFGF) but not external gene
      intervention. After incubation of human terminally differentiating keratinocytes,
      some of the surviving keratinocytes reverted from a differentiated to a
      dedifferentiated state, as evidenced by re-expression of biological markers of
      native keratinocyte stem cells (nKSCs), including beta(1)-integrin, CK19 and
      CK14. Moreover, these dedifferentiation-derived KSCs (dKSCs) showed an ability
      for high colony formation correlated with cell cycle analysis showing a marked
      accumulation in S phases, acquired a similar regional distribution of both
      alpha(6)-integrin and CD71 expression at the ultrastructural level, and had a
      increased proliferative capacity by releasing telomerase from nucleolar sites to
      nucleoplasmic distribution. However, on comparing dKSCs with nKSCs, 2 points seem
      noteworthy: (1) the proportion of transit amplifying cells in dKSCs treated with
      bFGF is much higher than that in nKSCs and (2) regional differences exist in the
      subcellular localization of telomerase in nKSCs and dKSCs. Most nKSCs showed a
      prominent nucleolar concentration of human telomerase reverse transcriptase
      expression, whereas most dKSCs showed a more diffuse intranuclear distribution of
      telomerase or even signal depletion at nucleoli relative to the general
      nucleoplasm. These results indicate that bFGF could induce the terminally
      differentiating epidermal keratinocytes to convert into their precursor cells,
      which offers a new approach for generating residual healthy stem cells for wound
      repair and regeneration.

PMID- 21720011
TI  - Hyperlipidemic guinea pig model: mechanisms of triglyceride metabolism disorder
      and comparison to rat.
AB  - Guinea pigs and rats are both common animal models for hyperlipidemia studies.
      However, many recent studies have suggested that rats do not develop
      hypertriglyceridemia in response to cholesterol feeding. In the present work, the
      differences in triglyceride metabolism between guinea pigs and rats were
      investigated. Feeding a high-fat diet containing 0.1% cholesterol and 10% lard
      for 4 weeks led to a significant increase in plasma total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), triglyceride (TG) and free fatty acid
      (FFA) in guinea pigs but not in rats. By contrast, hepatic TG levels in rats were
      greatly increased in response to the high-fat diet, while it remained unchanged
      in guinea pigs. Furthermore, the hepatic acyl CoA:diacylglycerol acyltransferase
      (DGAT) activity and microsomal triglyceride transfer protein (MTTP) mRNA levels
      in guinea pigs fed a high-fat diet were significantly higher than those in the
      control group, which implies an increased very-low-density lipoprotein (VLDL)-TG
      secretion rate in guinea pigs in response to a high-fat diet. Hepatic carnitine
      palmitoyltransferase-1 (CPT-1) activity and peroxisome proliferator-activated
      receptor-alpha (PPARalpha) mRNA levels were upregulated in guinea pigs, but not
      rats, fed a high-fat diet. These findings may explain the differences in plasma
      and hepatic TG concentrations between guinea pigs and rats. These results suggest
      that there are differences in triglyceride metabolism between the two species
      when fed high-fat diets.

PMID- 21720012
TI  - Tanshinone IIA attenuates seawater aspiration-induced lung injury by inhibiting
      macrophage migration inhibitory factor.
AB  - Inflammation takes responsibility for the seawater aspiration-induced lung
      injury. Tanshinone IIA (TIIA) can protect lipopolysaccharide-induced lung injury
      in mice through the inhibition of inflammation, but it is not reported whether
      TIIA have a protective effect on lung injury induced by seawater aspiration.
      Macrophage migration inhibitory factor (MIF) plays an important role in acute
      lung injury. In this study, we observed the effect of TIIA on the seawater
      aspiration-induced lung injury and the role of MIF in it. Seawater was aspirated
      into trachea of rats to make the lung injury model. TIIA was administered to
      investigate its beneficial effect on seawater-induced acute lung injury. The
      results showed that seawater aspiration led to hyoxemia, pulmonary edema,
      neutrophil infiltration, and lung histopathologic changes, with the elevated MIF
      expression in the lung tissues and plasma. However, these changes were attenuated
      by TIIA. In macrophage cells we also demonstrated that TIIA could inhibit MIF
      expression, nuclear factor kappaB (NF-kappaB) activity and release of interleukin
      6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) induced by seawater.
      Besides, pretreatment with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole
      acetic acid (ISO-1), the MIF antagonist, elevated NF-kappaB and cytokines induced
      by seawater were also reduced markedly. Furthermore, rMIF treatment alone
      increased the phosphorylation level of NF-kappaB and release of cytokines, which
      was almost abolished by TIIA. Taken together, our results suggested that TIIA
      exert a protective effect on the seawater aspiration-induced lung injury partly
      through downregulation of MIF and the subsequent NF-kappaB activity, as well as
      expression of IL-6 and TNF-alpha.

PMID- 21720013
TI  - Improving efficiency of adriamycin crossing blood brain barrier by combination of
      thermosensitive liposomes and hyperthermia.
AB  - Adriamycin (ADM)-encapsulated thermosensitive liposomes (ts-lip-ADM) and common
      liposomes (lip-ADM) were developed and evaluated. The encapsulation efficiency of
      the two liposomes were above 99%, and the average sizes of liposomes were about
      120 nm. Temperature-dependent drug release from loaded liposomes in vitro was
      investigated: more than 90% of loaded ADM was released from ts-lip-ADM within 30
      min at 42 degrees C, while less than 3% was released from lip-ADM at 42 degrees C
      beyond 120 min. An in vitro model of blood brain barrier (BBB) was established
      and evaluated by permeability and transendothelial electrical resistance (TEER).
      The model was employed to study the permeability of liposomes in vitro. The
      permeability of ts-lip-ADM could be increased significantly after the temperature
      was raised to 42 degrees C, which was about 10-16, 22-38, 38-45, 50-105 fold to
      that of ts-lip-ADM (37 degrees C), lip-ADM (42 degrees C), lip-ADM (37 degrees C)
      and free ADM, respectively. C6 glioma-bearing mice model was developed and used
      to evaluate body distribution and anti-tumor efficacy in vivo. Mice were IV
      injected at a drug dose of 10 mg/kg. After administration the heads of mice were
      heated in water bath at 42 degrees C for 30 min. The maximum brain concentration
      of ts-lip-ADM was 6.4, 3.7 fold compared with that of ADM solution and lip-ADM,
      respectively. The survival time of mice administered ts-lip-ADM (44 d) was
      remarkably longer than that of other three groups. This study indicates that ADM
      encapsulated thermosensitive liposomes combined hyperthermia could enhance ADM
      delivery across BBB and prolong survival time of glioma-bearing mice.

PMID- 21720014
TI  - High mobility group nucleosomal binding domain 2 protein protects bladder
      epithelial cells from Klebsiella pneumoniae invasion.
AB  - Due to the predominance of multiple-antibiotic-resistant Klebsiella pneumoniae
      strains, the search for new approaches for the prevention of K. pneumoniae
      infections is now under intensive investigation. The objective of the present
      study was to investigate the effects of high mobility group nucleosomal binding
      domain 2 (HMGN2) protein, which acts on the bladder epithelial cells T 24, on the
      invasion of K. pneumoniae 03183 and explore its possible mechanisms. Pretreatment
      with HMGN2 significantly reduced K. pneumoniae 03183 uptake by T 24 cells. In T
      24 cells, there were no detectable cytotoxic effects of HMGN2 at any
      concentration between 32 and 256 ug/ml after 2 h incubation. HMGN2 exhibited no
      appreciable antibacterial activity against K. pneumoniae 03183. Fluorescence
      microscopy and flow cytometry analysis revealed that HMGN2 blocked K. pneumoniae
      03183-induced actin polymerization. K. pneumoniae 03183-induced phosphorylation
      of extracellular signal-regulated kinase (ERK) and cofilin were prevented by
      pretreatment with HMGN2. These results indicated that pretreatment with HMGN2
      inhibited cofilin phosphorylation and then induced actin disruption which may
      block ERK phosphorylation. These changes led to inhibition of K. pneumoniae 03183
      invasion of T 24 bladder epithelial cells.

PMID- 21720015
TI  - Rb1 protects endothelial cells from hydrogen peroxide-induced cell senescence by
      modulating redox status.
AB  - Senescence of endothelial cells has been proposed to play an important role in
      endothelial dysfunction and atherogenesis. In the present study we aimed to
      investigate whether ginsenoside Rb1, a major constituent of ginseng, protects
      endothelial cells from H(2)O(2)-induced endothelial senescence. While H(2)O(2)
      induced premature senescent-like phenotype of human umbilical vein endothelial
      cells (HUVECs), as judged by increased senescence-associated beta-galactosidase
      (SA-beta-gal) activity, enlarged, flattened cell morphology and sustained growth
      arrest, our results demonstrated that Rb1 protected endothelial cells from
      oxidative stress induced senescence. Mechanistically, we found that Rb1 could
      markedly increase intracellular superoxide dismutase (Cu/Zn SOD/SOD1) activity
      and decrease the malondialdehyde (MDA) level in H(2)O(2)-treated HUVECs, and
      suppress the generation of intracellular reactive oxygen species (ROS).
      Consistent with these findings, Rb1 could effectively restore the protein
      expression of Cu/Zn SOD, which was down-regulated in H(2)O(2) treated cells.
      Taken together, our data demonstrate that Rb1 exhibits antioxidant effects and
      antagonizes H(2)O(2)-induced cellular senescence.

PMID- 21720016
TI  - alpha-Synuclein aggregation and transmission are enhanced by leucine-rich repeat
      kinase 2 in human neuroblastoma SH-SY5Y cells.
AB  - Formation of alpha-synuclein aggregates is a key step in Parkinson's disease
      pathogenesis although the etiology remains elusive. alpha-Synuclein is
      accumulated in degenerating neurons, leading to the production of filamentous
      inclusions such as Lewy bodies. However, the in vitro overexpression of alpha
      synuclein alone failed to induce inclusion bodies consisting of phosphorylated
      alpha-synuclein. The seeded aggregates-initiated polymerization of alpha
      synuclein and tau has been reported elsewhere. What molecule is an initiator of
      filamentous inclusions remains to be defined. Here, we report that leucine-rich
      repeat kinase 2 (LRRK2)-cotransfection together with alpha-synuclein enhance the
      aggregate formation, phosphorylation, release to extracellular media of alpha
      synuclein, and the cell-to-cell transmission into neighboring cells in human
      neuroblastoma SH-SY5Y cells. In cells transfected with alpha-synuclein alone, the
      proteins were distributed in the cytosol and did not form inclusions. On the
      other hand, the inclusions and phosphorylation of alpha-synuclein were formed in
      cells cotransfected with alpha-synuclein and LRRK2 G2019S mutant together. LRRK2
      G2019S-cotransfected PC12 cells also induced the aggregates. Furthermore, the
      cell-to-cell transmission of alpha-synuclein and the cell toxicity were also
      enhanced by either LRRK2 wild type or G2019S mutant, whereas the cell viability
      was not decreased in cells transfected with alpha-synuclein alone. These results
      suggest that overexpression of LRRK2, especially G2019S mutant, whose functions
      remain unclear, initiate the aggregate formation, release and transmission of
      alpha-synuclein, resulting in the propagation of alpha-synuclein to neighboring
      cells and reduction of cell viability.

PMID- 21720017
TI  - Synthesis and evaluation of stearylated hyaluronic acid for the active delivery
      of liposomes to liver endothelial cells.
AB  - Hyaluronic acid (HA) is a naturally-occurring ligand that can be useful for
      targeting liver endothelial cells. We describe herein the development of a new HA
      lipid conjugate for the efficient delivery of liposomes to liver endothelial
      cells. When free HA coated cationic liposomes were injected into mice, their
      accumulation in the liver was significantly decreased depending on the content of
      free HA, while accumulation in the lung was not significantly changed. When
      cationic liposomes modified with HA-stearylamine (HA-SA conjugate) were injected
      in mice, liver accumulation was increased depending on the amount of HA-SA
      conjugate and accumulation in the lung was drastically reduced, compared to non
      modified liposomes. Confocal imaging analyses showed that HA-SA modified
      liposomes were accumulated to a greater extent along with blood vessels than non
      modified liposomes, suggesitng that HA-SA modified liposomes are distributed in
      endothelial cells in the liver. Collectively, these findings indicate that an HA
      SA conjugate is a useful material that can be used to modify liposomes and for
      delivering bioactive liposomal cargoes to liver endothelial cells.

PMID- 21720018
TI  - Regulatory effect of cannabinoid receptor agonist on chemokine-induced lymphocyte
      chemotaxis.
AB  - Cannabinoids elicit biological responses through two types of specific receptors,
      CB1 and CB2. Immune cells including naive B-lymphocytes are known to selectively
      express peripheral cannabinoid receptors, CB2. Although the immunosuppressive
      effects of cannabinoids have become widely known, the mechanisms underlying their
      effects are not well understood. In this study, we demonstrated that splenic
      lymphocytes migrated toward a synthetic cannabinoid receptor agonist, WIN55,212
      2. There is an optimal concentration range for induction of lymphocyte migration
      and a high dose fails to induce cell migration. Furthermore, a high dose of
      WIN55,212-2 significantly inhibited CXCL12-induced chemotaxis of lymphocytes. The
      inhibitory effect was transient and reversible. The inhibition was also observed
      when purified B-lymphocytes were used for CXCL12-induced chemotaxis. These
      results provide novel information regarding the cellular mechanisms underlying
      the effects of cannabinoids on the immune system.

PMID- 21720019
TI  - Pharmacology and in vitro profiling of a novel peroxisome proliferator-activated
      receptor gamma ligand, Cerco-A.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma; NR1C3) is known as a
      key regulator of adipocytogenesis and the molecular target of thiazolidinediones
      (TZDs), also known as antidiabetic agents. Despite the clinical benefits of TZDs,
      their use is often associated with adverse effects including peripheral edema,
      congestive heart failure, and weight gain. Here we report the identification and
      characterization of a non-thiazolidinedione PPARgamma partial agonist, Cerco-A,
      which is a derivative of the natural product, (-)-cercosporamide. Cerco-A was
      found to be a binder of the PPARgamma ligand-binding domain in a ligand
      competitive binding assay and showed a unique cofactor recruitment profile
      compared to rosiglitazone. A crystal structure analysis revealed that Cerco-A
      binds to PPARgamma without direct hydrogen bonding to helix12. In PPARgamma
      transcriptional activation assay and an adipocyte differentiation assay, Cerco-A
      was a potent partial agonist of PPARgamma. After a 14-day oral administration,
      once per day of Cerco-A in Zucker diabetic fatty (ZDF) rats, an apparent decrease
      of plasma glucose and triglyceride was observed, as with pioglitazone. To
      evaluate drug safety, Cerco-A was administered for 13 days orally in non-diabetic
      Zucker fatty (ZF) rats. Each of the hemodilution parameters (hematocrit, red
      blood cells number, and hemoglobin), which are considered as undesirable effects
      of TZDs, was improved significantly compared to pioglitazone. While Cerco-A
      showed body weight gain, as with pioglitazone, Cerco-A had significantly lower
      effects on heart and white adipose tissues weight gain. The results suggest that
      Cerco-A offers beneficial effects on glycemic control with attenuated undesirable
      side effects.

PMID- 21720020
TI  - Intrathecal administration of AS1928370, a transient receptor potential vanilloid
      1 antagonist, attenuates mechanical allodynia in a mouse model of neuropathic
      pain.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is primarily expressed in
      central and peripheral terminals of non-myelinated primary afferent neurons. We
      previously showed that AS1928370, a novel TRPV1 antagonist that can prevent
      ligand-induced activation but not proton-induced activation, ameliorates
      neuropathic pain in rats without hyperthermic effect. In this study, we
      investigated its analgesic profile in mice. AS1928370 showed good oral
      bioavailability and high penetration into the brain and spinal cord in mice. The
      mean plasma-to-brain and plasma-to-spinal cord ratios were 4.3 and 3.5,
      respectively. Pretreatment with AS1928370 significantly suppressed both capsaicin
      induced acute pain and withdrawal response in hot plate test at 10-30 mg/kg per
      os (p.o.). At lower oral doses (0.3-1.0 mg/kg), AS1928370 improved mechanical
      allodynia in mice undergoing spinal nerve ligation. Intrathecal administration of
      AS1928370 (30 ug/body) also significantly suppressed mechanical allodynia. In
      addition, AS1928370 showed no effect on locomotor activity up to 30 mg/kg p.o.
      These results suggest that spinal TRPV1 has an important role in the transmission
      of neuropathic pain and that the central nervous system (CNS) penetrant TRPV1
      receptor antagonist AS1928370 is a promising candidate for treating neuropathic
      pain.

PMID- 21720021
TI  - Effects of grape seed proanthocyanidin on 5-hydroxytryptamine(3) receptors in NCB
      20 neuroblastoma cells.
AB  - Proanthocyanidin is a phenolic compound present in plants, that has antioxidant,
      antinociceptive, anti-emetic, and neuroprotective properties. We investigated the
      actions of proanthocyanidin from grape seeds on 5-hydroxytryptamine (5-HT)(3)
      receptors in NCB-20 neuroblastoma cells using a whole-cell voltage clamp
      technique. Co-treatment of proanthocyanidin (0.3-100 ug/ml) and 3 uM 5-HT (near
      EC(50)) produced a slight inhibition of 5-HT-induced inward peak current (I(5
      HT)) in NCB-20 cells, but pretreatment with proanthocyanidin for 30 s before
      application of 5-HT induced a much larger inhibition of I(5-HT) in an
      irreversible, concentration- and time-dependent manner (IC(50)=6.5+/-0.4 ug/ml,
      Hill coefficient=2.5+/-0.1). Proanthocyanidin also produced a concentration
      dependent inhibition of currents induced by 30 uM 5-HT, near-maximal
      concentration (IC(50)=22.1+/-0.4 ug/ml, Hill coefficient=2.4+/-0.1). High
      concentrations (?30 ug/ml) of proanthocyanidin caused a concentration-dependent
      inhibition of the activation and desensitization of currents induced by 30 uM 5
      HT. Further studies showed that pretreatment of 20 ug/ml proanthocyanidin caused
      not only a rightward shift of the dose-response curve for 5-HT (EC(50) shift from
      2.7+/-0.4 to 6.2+/-0.5 uM), but also a decreased E(max) (inhibition by 37.5+/
      1.3%). The proanthocyanidin-induced inhibition of 5-HT(3) receptors did not show
      a significant difference within the testing holding potential ranges (-50-+30
      mV). These results suggest that proanthocyanidin inhibits 5-HT(3) receptor
      function in NCB-20 cells in a noncompetitive mode, and that this inhibitory
      effect of proanthocyanidin probably contributes to the pharmacological actions of
      proanthocyanidin.

PMID- 21720022
TI  - Comparison of receptors and enzymes regulating cholesterol levels in liver
      between SHR/NDmcr-cp rats and normotensive Wistar Kyoto rats at ten weeks of age.
AB  - The spontaneously hypertensive rat (SHR)/NDmcr-cp (SHR-cp), which is a metabolic
      syndrome model rat, was reported to show hypercholesteremia, as compared with
      lean littermates. The serum total cholesterol level in SHR-cp at 18 weeks of age
      is higher than that of normotensive Wistar Kyoto rat (WKY), but that in SHR-cp at
      10 weeks of age is the same. The objective of this study is to clarify whether
      there are differences in the system regulating serum cholesterol levels between
      SHR-cp and WKY at 10 weeks of age. Total serum cholesterol levels, and
      cholesterol levels of high density lipoprotein (HDL), low density lipoprotein
      (LDL), and very low density lipoprotein (VLDL) were similar in the two strains.
      However, the cholesterol levels in the liver of SHR-cp were lower than those of
      WKY. Next, mRNA levels of receptors (scavenger receptor class B type 1 [SRB1],
      LDL receptor [LDLR]) involved in uptake from serum to liver or enzymes of
      cholesterol catabolism (CYP7A1 and CYP8B1) and biosynthesis (mevalonate
      pyrophosphate decarboxylases [MPD]) in liver were compared between SHR-cp and
      WKY. High levels of MPD and LDLR and low levels of SRB1 were shown in SHR-cp, as
      compared with WKY. CYP7A1 and CYP8B1 levels were similar between SHR-cp and WKY.
      These results suggest that the serum cholesterol level in SHR-cp by the balance
      or regulation between the rise in cholesterol uptake and reduction in cholesterol
      biosynthesis in the liver is the same as that in WKY.

PMID- 21720023
TI  - Thiazolidinediones are potent inducers of fibroblast growth factor 21 expression
      in the liver.
AB  - Fibroblast growth factor 21 (FGF21) is an effective metabolic regulator of
      glucose and lipid homeostasis in the context of insulin resistance, glucose
      intolerance and dyslipidemia in diabetic rodents and monkeys, and peroxisome
      proliferator-activated receptor alpha (PPARalpha) directly induces FGF21
      expression in the rodent liver. Recent findings suggest that the effects and
      regulation of FGF21 qualitatively differ between rodents and humans. Here, we
      examined the effects of PPARalpha and PPARgamma agonists on FGF21 mRNA expression
      in the mouse liver and in cultured hepatocytes. Intraperitoneal injection of both
      bezafibrate and pioglitazone induced FGF21 mRNA expression in the mouse liver.
      Rosiglitazone and pioglitazone as well as bezafibrate significantly induced FGF21
      mRNA expression in cultured mouse hepatocytes. On the other hand, both
      rosiglitazone and pioglitazone significantly induced, whereas bezafibrate did not
      affect FGF21 mRNA expression in the human liver carcinoma cell line HepG2.
      Bezafibrate significantly induced pyruvate dehydrogenase kinase 4 mRNA
      expression, suggesting that HepG2 cells are sensitive to bezafibrate like the
      mouse liver. Our findings suggest that PPARgamma-activating antidiabetic drugs
      such as rosiglitazone and pioglitazone induce FGF21 expression in mouse and human
      hepatocytes, and that PPARgamma rather than PPARalpha might play an important
      role in human FGF21 production.

PMID- 21720024
TI  - Involvement of bradykinin in trypsin-induced urinary bladder contraction in
      cyclophosphamide-treated rats.
AB  - Protease-activated receptor-2 (PAR-2) is activated by serine proteases, such as
      trypsin and mast cell tryptase. Previous studies have demonstrated that both
      trypsin and PAR-2 activating peptide contract isolated rat urinary bladder
      preparations, however, the mechanisms are not fully understood. In the present
      study, we examined the role of bradykinin in contractions induced by trypsin and
      the PAR-2 agonist 2-furoyl-LIGRL-NH(2) in urinary bladders isolated from control
      or cyclophosphamide (CYP)-induced cystitis rats. The contractile effects of
      trypsin were significantly greater in the preparations obtained from CYP-treated
      rats than in those from controls. The bradykinin B2 receptor antagonist Hoe 140
      did not affect trypsin-induced contractions in control rat bladders, whereas it
      significantly reduced the contractile effects of trypsin on bladders from CYP
      treated rats. On the other hand, Hoe 140 failed to affect contractions induced by
      the PAR-2 agonist 2-furoyl-LIGRL-NH(2). These results suggest that the actions of
      trypsin on urinary bladders in cystitis rats are partly exerted through
      stimulation of bradykinin B2 receptor in a PAR-2-independent manner. This
      mechanism seems to be involved in the enhancement of trypsin-induced bladder
      contractions observed after induction of cystitis with CYP in rats.

PMID- 21720025
TI  - High-performance liquid chromatographic assay for the determination of nilotinib
      in human plasma.
AB  - A precise and convenient high-performance liquid chromatography (HPLC) method has
      been established to assay nilotinib in human plasma. Chromatographic separation
      of nilotinib was performed on a LiChrosphere((r))100 RP-18(e) column (250 mm*4.0
      mm, 5 um) using a mixture of acetonitrile and 0.01 M phosphate buffer (pH 3.0)
      (42 : 58, v/v) under isocratic conditions at a flow rate of 1.0 ml/min with
      ultraviolet (UV) detection at 266 nm. The calibration curve showed linearity at
      concentrations between 250 ng/ml and 5000 ng/ml (r(2)>0.999). The mean+/-S.D.
      absolute recovery of nilotinib from plasma was 99.2+/-3.3%. The coefficients of
      variation of both intra- and inter-day precision were below 9.1%. These results
      indicate that this new HPLC-based quantification may be useful for therapeutic
      drug monitoring of nilotinib to help manage treatment in patients with chronic
      myeloid leukemia in clinical practice.

PMID- 21720026
TI  - Poly(amidoamine) dendrimers increase antifungal activity of clotrimazole.
AB  - Clotrimazole (CLO) is a local imidazolic antifungal agent. A major problem
      associated with the successful formulation of effective dosage forms containing
      CLO is its poor aqueous solubility, which presents a hindrance for the local
      availability of CLO and limits the effective antifungal therapy. In the present
      study, the effects of various concentrations of poly(amidoamine) (PAMAM)
      dendrimers generation 2 (G2) and generation 3 (G3) with amine (PAMAM-NH(2)) or
      hydroxyl surface groups (PAMAM-OH) on aqueous solubility and antifungal activity
      of CLO were studied. The obtained results showed that all tested PAMAM dendrimers
      improved the solubility of CLO and the more potent were PAMAM-NH(2) dendrimers.
      The increase in solubility of CLO was highest at dendrimer concentration of 10
      mg/ml. Microbiology studies indicated that only PAMAM-NH(2) dendrimers
      significantly increased the antifungal activity of CLO (a 4-32-fold increase in
      the antifungal activity compared to pure CLO) and the most potent was dendrimer
      PAMAM-NH(2) G2. These observations indicate that PAMAM dendrimers might be
      considered as potential carriers of CLO and provide further impetus to evaluate
      these polymers for use in basic drug delivery studies and to design semisolid
      dosage forms based on dendrimers with antimicrobial drugs, like CLO.

PMID- 21720027
TI  - Sugar-binding properties of the two lectin domains of LEC-1 with respect to the
      Galbeta1-4Fuc disaccharide unit present in protostomia glycoconjugates.
AB  - Galbeta1-4Fuc disaccharide unit was recently reported to be the endogenous
      structure recognized by the galectin LEC-6 isolated from the nematode
      Caenorhabditis elegans. LEC-1, which is another major galectin from this
      organism, is a tandem repeat-type galectin that contains two carbohydrate
      recognition domains, the N-terminal lectin domain (LEC-1Nh) and the C-terminal
      lectin domain (LEC-1Ch), and was also found to have an affinity for the Galbeta1
      4Fuc disaccharide unit. In the present study, we compared the binding strengths
      of LEC-1, LEC-1Nh, and LEC-1Ch to Galbeta1-4Fuc, Galbeta1-3Fuc, and Galbeta1
      4GlcNAc units as well as to LEC-6-ligand N-glycans by using frontal affinity
      chromatography (FAC) analysis. The two lectin domains of LEC-1 exhibited the
      highest affinity for Galbeta1-4Fuc, though sugar-binding properties differed
      somewhat between LEC-1Nh and LEC-1Ch. Furthermore, these two domains had
      significantly lower affinities for the LEC-6-binding glycans. These results
      suggest that the endogenous recognition unit of LEC-1 is likely to be Galbeta1
      4Fuc, and that the endogenous ligands for LEC-1 are different from those for LEC
      6.

PMID- 21720028
TI  - Galectin LEC-6 interacts with glycoprotein F57F4.4 to cooperatively regulate the
      growth of Caenorhabditis elegans.
AB  - To study the endogenous counterpart of LEC-6, a major galectin in Caenorhabditis
      elegans, the proteomic analysis of glycoproteins captured by an immobilized LEC-6
      column was performed using the nano liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) technique. A protein recovered in a significant amount
      was determined to be either F57F4.3 or F57F4.4, although the method used could
      not determine which protein was the actual counterpart. Because the knockdown of
      the F57F4.3/4 genes in C. elegans is reported to cause growth retardation, we
      performed a double knockdown of the lec-6 and F57F4.3/4 genes. Although the RNA
      mediated interference (RNAi) of lec-6 led to no obvious phenotype, the RNAi of
      both the lec-6 and F57F4.3/4 genes led to a significant reduction in growth rate
      when compared to the RNAi of F57F4.3/4 alone. Furthermore, to clarify which
      protein, F57F4.3 or F57F4.4, was responsible for the retarded growth, the levels
      of the F57F4.3/4 proteins expressed in a C. elegans wild type and a mutant
      lacking part of the F57F4.3 gene were compared. The levels of protein expressed
      by the wild type and the mutant were not significantly different, suggesting that
      the F57F4.3 protein contributes very little to growth retardation and that the
      major glycoprotein that interacts with LEC-6 is the F57F4.4 protein. These
      results suggest that binding with LEC-6 supports the function of F57F4.4 and that
      their cooperative functioning regulates the growth of C. elegans.

PMID- 21720029
TI  - Xanthine oxidase inhibitory activities and crystal structures of methoxyflavones
      from Kaempferia parviflora rhizome.
AB  - Kaempferia parviflora (KP), a Zingiberaceae plant, is used as a folk medicine in
      Thailand for the treatment of various symptoms, including general pains, colic
      gastrointestinal disorders, and male impotence. In this study, the inhibitory
      activities of KP against xanthine oxidase (XOD) were investigated. The extract of
      KP rhizomes showed more potent inhibitory activity (38% at 500 ug/ml) than those
      of the other Zingiberaceae plants tested. Ten methoxyflavones were isolated from
      the KP extract as the major chemical components and their chemical structures
      were elucidated by X-ray crystallography. The structurally confirmed
      methoxyflavones were subjected to the XOD inhibitory test. Among them,
      3,5,7,4',5'-pentamethoxyflavone and 3',4',5,7-tetramethoxyflavone showed
      inhibitory activities (IC(50) of 0.9 and >4 mM, respectively) and their modes of
      inhibition are clarified as competitive/non-competitive mixed type. To the best
      of our knowledge, this is the first report to present the inhibitory activities
      of KP, 3,5,7,4',5'-pentamethoxyflavone and 3',4',5,7-tetramethoxyflavone against
      XOD.

PMID- 21720030
TI  - Sulfation of estradiol in human epidermal keratinocyte.
AB  - Epidermis is one of the well-known estrogen target tissues. Information regarding
      estrogen metabolism in epidermis is still very limited compared to that of
      estrogen action. In the breast cancer tissue, 17beta-estradiol (E(2)) is
      inactivated by sulfation and the expression level of estrogen sulfotransferase
      (SULT1E1) is inversely correlated with its malignancy. However, there is little
      datum about inactivation of estradiol in skin. In order to detect and measure
      E(2) and its metabolites simultaneously, we established an assay method with
      radio HPLC. A majority of [(3)H] labeled E(2) was converted to E(2) sulfate in
      normal human epidermal keratinocyte (NHEK) cells. The estimated activity of
      sulfotransferase toward E(2) at 20 nM was 0.11+/-0.01 (pmol/min/mg protein).
      Significant induction of estrogen sulfotransferase activity was observed in
      calcium-differentiated NHEK cells (0.58+/-0.07 (pmol/min/mg protein)). The gene
      expression of SULT1E1 was fifteen-fold higher in differentiated keratinocyte than
      in proliferating keratinocyte, whereas that of steroid sulfatase was reduced.
      These results suggest that E(2) inactivation is primarily mediated by SULT1E1 in
      keratinocyte and E(2) action is likely suppressed in epidermal differentiation.

PMID- 21720031
TI  - Naturally occurring iridoids and secoiridoids. An updated review, part 4.
AB  - A compilation of new naturally occurring iridoids and secoiridoids including
      their glycosides, esters, aglycones, derivatives and dimers reported during mid
      2008-2010 is provided with available physical and spectral data: mp, [alpha](D),
      UV, IR, circular dichroism (CD), (1)H- and (13)C-NMR as well as natural source
      with family and references. The important bioactivity of new and known iridoids
      and secoiridoids reported during this period is also highlighted.

PMID- 21720032
TI  - Plastoquinones from Sargassum yezoense; chemical structures and effects on the
      activation of peroxisome proliferator-activated receptor gamma.
AB  - Four new plastoquinones, together with two known compounds, sargahydroquinoic
      acid and sargaquinoic acid, were isolated from the brown alga, Sargassum yezoense
      collected from the eastern coast of Korea. The structures of these compounds were
      elucidated based on spectroscopic analyses including NMR and MS. Their structures
      designated as meroterphenol A (1), B (2), C (3) and D (4) were characterized by a
      6-methyl-1,4-benzohydroquinone moiety with an oxygenated diterpenoic acid chain.
      Meroterphenols A-D showed potent activation effects on peroxisome proliferator
      activated receptor gamma (PPARgamma).

PMID- 21720033
TI  - Quantitation of L-arginine and asymmetric dimethylarginine in human plasma by LC
      selective ion mode-MS for Type 2 diabetes mellitus study.
AB  - The article reports a simple, sensitive and fast LC/MS method for the analysis of
      L-arginine (L-Arg), asymmetric dimethylarginine (ADMA) and symmetric
      dimethylarginine (SDMA) in human plasma. The homoarginine was used as the
      internal standard (IS). The chromatographic separation was achieved on C18(150
      mm*2.1 mm, 5 um) column with a mobile phase consisting of ammonium acetate (0.25
      mmol/l) and methanol (93 : 7, v/v), at a flow rate of 0.2 ml/min. L-Arg, ADMA and
      SDMA were well separated by LC/MS with selective ion mode (SIM). The method was
      successfully applied to type 2 diabetes mellitus (T2DM) study. Twenty-one healthy
      controls and twenty-two T2DM patients before and after treatment two years were
      investigated. The results indicated that the level of ADMA in T2DM was
      significantly higher than that in healthy controls. Furthermore, ADMA has
      important association with the development of cardiovascular diseases.

PMID- 21720034
TI  - Dissolution-enhancing mechanism of alkalizers in poloxamer-based solid
      dispersions and physical mixtures containing poorly water-soluble valsartan.
AB  - The purpose of this study was to investigate the effects of alkalizers in
      dissolution rate and crystal structure of valsartan (VAL) in Poloxamer 407 (POX)
      based solid dispersions (SD). VAL, a poorly-water soluble drug was selected as a
      model drug because of its low solubility at low pH. The POX-based SDs containing
      alkalizers (Na2CO3, MgO, meglumine and arginine) were prepared by melting method.
      The dissolution tests were performed using the United States Pharmacopeia (USP)
      paddle II method in enzyme-free simulated gastric fluid (pH 1.2) for 2 h.
      Microenvironmental pH (pH(M)) was examined potentiometrically by using a surface
      pH electrode. Dissolution rate of SD incorporating Na2CO3 was drastically
      increased. The differential scanning calorimetry (DSC) and powder X-ray
      diffraction (PXRD) data indicated that crystalline structure of VAL in SD was
      transformed to amorphous form by the addition of alkalizers but could not explain
      the differences in the dissolution rates. The molecular interaction between VAL
      and Na2CO3 was observed in the Fourier transform infrared spectroscopy (FT-IR)
      spectra by the shift of C=O band from 1732 to 1719 cm-1 and the disappearance of
      carbonyl group at 1598 cm-1. Furthermore, Na2CO3 efficiently modulated pH(M) by
      providing a favorable microenvironment for drug dissolution. A combination of SD
      method and use of alkalizer is a promising approach to modulate release rate of
      poorly water-soluble and ionizable drug with an aid of changes of drug
      crystallinity, molecular interaction and pH(M).

PMID- 21720035
TI  - Synthesis, characterization and biological evaluation of platinum(II) complexes
      with a chiral N-monosubstituted 1,2-cyclohexyldiamine derivative.
AB  - Eight platinum(II) compounds with a new chiral ligand, 2-(((1R,2R)-2
      aminocyclohexylamino)methyl)phenol (HL), were designed, prepared and spectrally
      characterized. All compounds showed better aqueous solubility than cisplatin and
      oxaliplatin. In vitro cytotoxicity of these compounds against human HepG-2, MCF
      7, A549 and HCT-116 cell lines was evaluated. Results indicated that all
      compounds showed cytotoxicity against A549 and HepG-2 cell lines. Particularly,
      compounds B1 and B8, which have CF3SO3- and (CH3)3COCH2COO(-) as leaving groups,
      respectively, exhibited better cytotoxicitiy than that of carboplatin in these
      two cell lines.

PMID- 21720036
TI  - seco-limonoids and quinoline alkaloids from Raputia heptaphylla and their
      antileishmanial activity.
AB  - A novel seco-limonoid, rel-(1S,5R,9S,7R,8S,9R,10S,11R,13S,14R,15R,17R)-11,19
      dihydroxy-7-acetoxy-7-deoxoichangin (raputiolide) (1), and two novel quinolone
      alkaloids N-methyl-2-phenoxyquinolin-4(1H)-one (heptaphyllone A) (2) and 6
      methylbenzofuro[2,3-b]quinolin-4(1H)-one (heptaphyllone B) (3), along with the
      known seco-limonoid ichangin (4), were isolated from Raputia heptaphylla PITTIER
      (Rutaceae) stem bark. Five known alkaloids, N-methyl-8-methoxyflindersine (5),
      skimmianine (6), kokusaginine (7), dictamnine (8) and flindersiamine (9), were
      also isolated from R. heptaphylla leaves. Their structures were established on
      the basis of full spectroscopic data interpretation supported by data from the
      pertinent literature. seco-Limonoid 1 configuration was determined by enhanced
      nuclear Overhauser effect spectroscopy (NOESY) experiments and density functional
      theory (DFT) molecular modeling. The antileishmanial effect of the isolated
      compounds was evaluated on Leishmania Viannia panamensis (promastigotes and
      amastigotes). Whereas alkaloids 2-3, 6-8 and limonoid 4 exhibited no significant
      parasitocide activity against internalized L. (V.) panamensis amastigotes,
      limonoid 1 and alkaloid 5 had leishmanicidal activity on intracellular
      amastigotes (EC50: 8.7 ug/ml) and promastigotes (EC(50): 14.3 ug/ml),
      respectively.

PMID- 21720037
TI  - Steric and allosteric effects of fatty acids on the binding of warfarin to human
      serum albumin revealed by molecular dynamics and free energy calculations.
AB  - Human serum albumin (HSA) binds with drugs and fatty acids (FAs). This study was
      initiated to elucidate the relationship between the warfarin binding affinity of
      HSA and the positions of bound FA molecules. Molecular dynamics simulations of 11
      HSA-warfarin-myristate complexes were performed. HSA-warfarin binding free energy
      was then calculated for each of the complexes by the molecular mechanics-Poisson
      Boltzmann surface area (MM-PBSA) method. The results indicated that the magnitude
      of the binding free energy was smaller in HSA-warfarin complexes that had 4 or
      more myristate molecules than in complexes with no myristate molecules. The
      unfavorable effect on the HSA-warfarin binding affinity was caused sterically by
      the binding of a myristate molecule to the FA binding site closest to the
      warfarin binding site. On the other hand, the magnitude of HSA-warfarin binding
      free energy was largest when 3 myristate molecules were bound to the high
      affinity sites. The strongest HSA-warfarin binding was attributable to favorable
      entropic contribution related to larger atomic fluctuations of the amino acid
      residues at the warfarin binding site. In the binding of 2 myristate molecules to
      the sites with the highest and second-highest affinities, allosteric modulation
      that enhanced electrostatic interactions between warfarin and some of the amino
      acid residues around the warfarin binding site was observed. This study clarified
      the structural and energetic properties of steric/allosteric effects of FAs on
      the HSA-warfarin binding affinity and illustrated the approach to analyze protein
      ligand interactions in situations such that multiple ligands bind to the other
      sites of the protein.

PMID- 21720038
TI  - Development of a rapid process monitoring method for dry-coated tableting process
      by using near-infrared spectroscopy.
AB  - A nondestructive transmittance near-infrared (NIR) method for detecting off
      centered cores in dry-coated (DC) tablets was developed as a monitoring system in
      the DC tableting process. Caffeine anhydrate was used as a core active
      pharmaceutical ingredient (API), and DC tablets were made by the direct
      compression method. NIR spectra were obtained from these intact DC tablets using
      the transmittance method. The reference assay was performed with HPLC.
      Calibration models were generated by partial least squares (PLS) regression and
      principal component regression (PCR) utilizing external validations. Hierarchical
      cluster analysis (HCA) of the results confirmed that NIR spectroscopy correctly
      detected off-centered cores in DC tablets. We formulated and used the Centering
      Index (CI) to evaluate the precision of core alignment and generated an NIR
      calibration model that could correctly predict this index. The principal
      component (PC) 1 loading vector of the final calibration model indicated that it
      could specifically detect the misalignment of tablet cores. The model also had
      good linearity and accuracy. The CIs of unknown sample tablets predicted by the
      final calibration model and those calculated through the HPLC analysis were
      closely parallel with each other. These results demonstrate the validity of the
      final calibration model and the utility of the transmittance NIR spectroscopic
      method developed in this study as a monitoring system in DC tableting process.

PMID- 21720039
TI  - Microbial Transformations of (+)-Isomenthol by Fusarium lini and Rhizopus
      stolonifer.
AB  - Microbial transformation of (+)-isomenthol (1) by various strains of fungi was
      investigated. Fusarium lini has successfully converted compound 1 into a new
      metabolite, 5alpha-hydroxyisomenthol (2), and a known metabolite, 1alpha
      hydroxyisomenthol (3), whereas incubation with Rhizopus stolonifer only yielded
      metabolite 3. The transformed metabolites were structurally characterized on the
      basis of their spectral data.

PMID- 21720040
TI  - 2-Acyl-tetrahydroisoquinoline-3-carboxylic acids: lead compounds with triple
      actions, peroxisome proliferator-activated receptor alpha/gamma agonist and
      protein-tyrosine phosphatase 1B inhibitory activities.
AB  - 2-Acyl-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and
      biologically evaluated. (S)-2-(2,4-Hexadienoyl)-7-[2-(5-methyl-2-phenyloxazol-4
      yl)ethoxy]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14) showed
      peroxisome proliferator-activated receptor gamma (PPARgamma) and PPARalpha
      agonist activities and protein-tyrosine phosphatase 1B (PTP-1B) inhibitory
      activities. PPARgamma agonist activity of 14 was comparable to that of
      rosiglitazone, and PTP-1B inhibitory activity was about 10-fold weaker than that
      of ertiprotafib, a PTP-1B inhibitor. Compound 14 showed high oral absorption in
      rats and potent hypoglycemic effects in KK-A(y) mice. In conclusion, 14 would be
      an excellent lead compound for a new type of anti-diabetic drug with triple
      actions.

PMID- 21720041
TI  - Inhibition of restriction enzymes EcoRI, BamHI and HindIII by
      phenethylphenylphthalimides derived from thalidomide.
AB  - We discovered inhibitors of the restriction enzymes EcoRI, BamHI and HindIII by
      screening our library of compounds with a phenethylphenylphthalimide skeleton,
      based on alpha-glucosidase inhibitors and liver X receptor antagonists derived
      from thalidomide. Structural development afforded the potent restriction enzyme
      inhibitors 25 and 26.

PMID- 21720042
TI  - Reinvestigation of the synthesis of isoliquiritigenin: application of Horner
      Wadsworth-Emmons reaction and Claisen-Schmidt condensation.
AB  - Isoliquiritigenin [ILG, (E)-1] was readily prepared via the Horner-Wadsworth
      Emmons reactions using beta-ketophosphonates 5a, b. An improved protocol for the
      synthesis of (E)-1 via the Claisen-Schmidt condensation was also presented.

PMID- 21720043
TI  - Medicinal Flowers. XXXII. Structures of oleanane-type triterpene saponins,
      perennisosides VIII, IX, X, XI, and XII, from the flowers of Bellis perennis.
AB  - Five new triterpene saponins perennisosides VIII (1), IX (2), X (3), XI (4), and
      XII (5) were isolated from the MeOH-eluated fraction of the methanolic extract
      from the flowers of Bellis perennis. The MeOH-eluted fraction of the methanolic
      extract from the flowers of B. perennis was found to inhibit gastric emptying in
      olive oil-loaded mice at a dose of 200 mg/kg, per os (p.o.). The stereostructures
      of 1-5 were elucidated on the basis of chemical and spectroscopic evidence.

PMID- 21720044
TI  - Pseuduvarines A and B, two new cytotoxic dioxoaporphine alkaloids from
      Pseuduvaria rugosa.
AB  - Pseuduvarines A (1) and B (2), two new dioxoaporphine alkaloids with an amino
      moiety, were isolated from the stem bark of Pseuduvaria rugosa and their
      structures were elucidated by combination of 2D-NMR spectroscopic analysis.
      Pseuduvarines A (1) and B (2) showed cytotoxicity against MCF7, HepG2, and HL-60
      (1: IC50, 0.9, 21.7, and >50.0 uM, respectively, 2: IC50 >50.0, 15.7, and 12.4
      uM, respectively).

PMID- 21720045
TI  - New prenylated C6-C3 compounds from the twigs of Illicium anisatum.
AB  - Two new prenylated C6-C3 compounds, cycloillicinone (1) and 4-allyl-2-methoxy-6
      (2-methylbut-3-en-2-yl)phenol (2), were isolated from the twigs of Illicium
      anisatum, and their structures were determined by 2D-NMR methods. Cycloillicinone
      (1) is a unique prenylated C6-C3 that is appended with an additional geranyl
      unit. Compound 2 was found to show moderate neurite-outgrowth promoting activity
      in primary cultured rat cortical neurons at a concentration of 10 uM.

PMID- 21720046
TI  - Tareciliosides H-M: further cycloartane glycosides from leaves of Tarenna
      gracilipes.
AB  - From the 1-BuOH-soluble fraction of a MeOH extract of leaves of Tarenna
      gracilipes, collected in Okinawa, six further new cycloartane glycosides, named
      tareciliosides H-M (1-6), were isolated. Their structures were established
      through a combination of spectroscopic analyses.

PMID- 21720047
TI  - Oxidative photodecarboxylation of alpha-hydroxycarboxylic acid derivatives with
      FSM-16 under visible light irradiation of fluorescent lamp.
AB  - Hydroxycarboxylic acids were converted to the corresponding carbonyl compounds
      under aerobic photo-oxidative conditions in the presence of FSM-16 under visible
      light irradiation by a fluorescent lamp. This synthetic protocol is the first
      example of FSM-16 functioning as a photocatalyst by visible light.

PMID- 21720048
TI  - Veramadines A and B, New Steroidal Alkaloids from Veratrum maackii var.
      japonicum.
AB  - Two new steroidal alkaloids possessing a cevanine-type skeleton, veramadines A
      (1) and B (2), were isolated from the aerial parts of Veratrum maackii var.
      japonicum. The structures of 1 and 2 were elucidated on the basis of their
      spectroscopic data.

PMID- 21720049
TI  - Effects of GH assay standardization on evaluation of treatment outcomes for
      acromegaly in Japan.
AB  - In Japan, the growth hormone (GH) assay has been standardized since April 2005
      through use of a uniform recombinant human GH (rhGH) standard.  Since then, GH
      values measured using the rhGH standard have been approximately 40% lower than
      previous values measured using kit standards based on the WHO standards for hGH
      of pituitary origin.  However, the Japanese criteria for evaluating treatment
      outcomes for acromegaly have remained the same: a nadir GH during a 75 g OGTT <1
      ug/L is considered cured, 1<=GH<2.5ug/L is considered inadequately controlled,
      and >=2.5 ug/L is considered poorly controlled, instead of these levels were
      lowered to 60%, i.e. from 1 to 0.6 ug/L for cured and from 2.5 to 1.5ug/L for
      inadequately controlled (termed as "newly proposed criteria" in this study).  We
      investigated the effects of standardization of the GH assay on the evaluation of
      post-surgical disease activity in 50 patients with acromegaly (M/F 19/31, 21-72
      yr.).  Post-surgical nadir GH levels during OGTT were positively correlated with
      the IGF-I SD score 3 months after TSS.  Five of 6 patients whose post-surgical
      nadir GH levels ranged between 0.6 and 1 ug/L had normal serum IGF-I levels 3
      months after TSS.  Rates of improvement in glucose metabolism did not differ when
      patients were classified based on the present criteria vs. the newly proposed
      criteria.  In conclusion, the current Japanese remission criteria for acromegaly
      still accurately reflect post-surgical disease activity in most patients, though
      long-term observation is still required.

PMID- 21720050
TI  - Identification by array-Comparative Genomic Hybridization (array-CGH) of a large
      deletion of luteinizing hormone receptor gene combined with a missense mutation
      in a patient diagnosed with a 46,XY disorder of sex development and application
      to prenatal diagnosis.
AB  - This paper reports the case of an infant presenting with sexual ambiguity at
      birth.  The child presented with labia majora synechia, thready genital tubercle
      and perineal hypospadias.  The karyotype was 46,XY.  Low testosterone levels with
      no response to hCG administration, associated with high LH level for her age,
      high FSH level, high inhibin B levels and normal AMH indicated a lack of LH
      receptivity and prompted us to screen the LHCGR gene for mutations.  A previously
      described missense mutation (p.Cys131Arg) was identified at homozygous state in
      the propositus and at heterozygous state in the mother.  This variation, however,
      was not found in the father.  Our attention was drawn by the presence of several
      single nucleotide polymorphisms (SNPs), identified at homozygous state without
      any paternal contribution from exon 1 to exon 10 of LHCGR, suggesting a paternal
      deletion.  Array DNA analysis was performed revealing a large deletion extending
      from 61,493 to 135,344 bp and including the LHCGR gene.  Adequate genetic
      counselling was provided.  This paper describes the first application of prenatal
      diagnosis in LHCGR deficiency for 46,XY disorders of sex development with the
      subsequent delivery of a normal baby.

PMID- 21720051
TI  - Detection of glucokinase gene defects in non-obese Japanese children diagnosed
      with diabetes by school medical examinations.
AB  - We examined children who were diagnosed with asymptomatic type 2 diabetes by
      school medical examinations to investigate the existence of glucokinase (GCK)
      gene defects in this group. Among 20 children diagnosed with asymptomatic type 2
      diabetes by school medical examinations between 2003 and 2009 at our 2 hospitals,
      8 were classified as non-obese type. Among them, we screened 5 children (2 boys
      and 3 girls; age: 8-13 years) who had mild elevation of fasting plasma glucose
      (108-134 mg/dL) with slightly high internationally standardized HbA1c levels (6.3
      6.9%) at first close examination. Written informed consent was obtained and all
      families agreed to participate in this study. We found 4 different mutations
      (G223S, G81C, S336X and T228M) in 4 of the examined children. The blood glucose
      control levels had not become worse in any children during the 2-6 years follow
      up period. The inheritance of diabetes with GCK gene defect was later confirmed
      in 1 family. These results suggest that GCK gene defects exist in non-obese
      children who are diagnosed with asymptomatic diabetes by school medical
      examinations. Cases of diabetes that are caused by GCK mutations may not be as
      rare in Japanese subjects as previously described and could be found in patients
      tentatively diagnosed as type 2 diabetes.

PMID- 21720052
TI  - Arigato to the rest of the world.

PMID- 21720053
TI  - Changes of upper gastrointestinal symptoms and endoscopic findings in Japan over
      25 years.
AB  - BACKGROUND AND AIMS: In Japan, the prevalence of Helicobacter pylori infection
      has decreased recently, but there has been little longitudinal research on the
      changes of symptoms and endoscopic findings over many years. The aim of this
      study was to evaluate the changes in endoscopic findings and symptoms over time
      in patients undergoing upper gastrointestinal endoscopy for assessment of upper
      abdominal symptoms. METHODS: Over a period of 25 years, between 1981 and 2005, we
      performed three investigations (1981-2, 1990-1 and 2004-5) on the symptoms and
      endoscopic findings of patients undergoing endoscopy at Kawasaki Medical School
      Hospital for the assessment of upper abdominal symptoms. RESULTS: The most common
      complaint for all ages was "discomfort and/or pain". Over time, the percentage of
      patients complaining of "heartburn" increased almost 5-fold. With respect to
      endoscopic findings, the prevalence of peptic ulcers decreased, whereas the
      detection of no abnormalities and the detection of erosive esophagitis increased.
      CONCLUSION: In the future in Japan, there will be fewer patients with peptic
      ulcers and more patients with gastro-esophageal reflux disease or dyspeptic
      patients who display no endoscopic abnormal findings.

PMID- 21720054
TI  - Can pleuropulmonary paragonimiasis be cured by only the 1st set of chemotherapy?
      Treatment outcome and clinical features of recently developed pleuropulmonary
      paragonimiasis.
AB  - PURPOSE: Most patients with pleuropulmonary paragonimiasis can be cured by the
      initial single set of Praziquantel (PZQ) treatment. However, several cases have
      been reported to have unsatisfactory responses to the initial PZQ treatment. The
      objective of this study was to evaluate the clinical findings of patients with
      pleuropulmonary paragonimiasis who needed additional PZQ treatment after the 1st
      set chemotherapy. PATIENTS AND METHODS: Thirty-two patients who were diagnosed
      with pleuropulmonary paragonimiasis at our institution between 2003 and 2008 were
      retrospectively reviewed. RESULTS: All patients were treated initially with PZQ
      for 3 days (1st set chemotherapy). Twenty-four patients (75.0%) showed
      improvement in respiratory symptoms and pulmonary involvements. However, eight
      patients (25.0%) suffered from relapsed respiratory symptoms and pleural
      effusion. For these patients, an additional 2nd set PZQ treatment resulted in the
      resolution of the symptoms and pulmonary involvements. The characteristics of
      patients who needed multi-set treatments were as follows; longer duration of
      respiratory symptoms (single vs multi-set treatment group; 6.67 +/- 8.08 vs 17.86
      +/- 11.84 weeks, p=0.009), higher IgG titer (optical density, O.D.) for
      Pargonimus westermani (ELISA O.D. for PW, 0.54 +/- 0.19 vs 0.88 +/- 0.16 O.D.,
      p=0.001) and higher frequency of multiple pulmonary lesions (% of patients with
      multiple lesions; 16.7% vs 50.0%, p=0.059). CONCLUSION: The patients who had a
      longer duration of respiratory symptoms, higher ELISA titer for PW and/or
      multiple pulmonary lesions needed an additional PZQ treatment after the 1st set
      of chemotherapy. Close follow-up after the initial treatment is necessary
      especially for such patients.

PMID- 21720055
TI  - A prospective evaluation of adult men with iron-deficiency anemia in Korea.
AB  - OBJECTIVE: Iron-deficiency anemia (IDA) is the most common nutritional deficiency
      worldwide. However, the information concerning various causes of IDA in adult men
      is still insufficient. The aim of our study was to evaluate adult men with IDA.
      METHODS: We prospectively studied 206 adult men with IDA. All subjects had a
      direct history taken and underwent a physical examination.
      Esophagogastroduodenoscopy was performed in most patients, and colonoscopy was
      conducted if no lesion causing IDA was found or the fecal occult blood test was
      positive. RESULTS: The history of prior gastrectomy and blood-letting cupping
      therapy that probably had caused IDA were reported in 24 (11.7%) and 11 (5.3%)
      patients, respectively. In terms of potential causes of IDA, 68 (33.0%) patients
      were found to have upper gastrointestinal disorders (34 peptic ulcers, 17 erosive
      gastritis, 16 gastric cancers, and one gastrointestinal stromal tumor).
      Colonoscopy showed 42 (20.4%) clinically relevant lesions that probably caused
      IDA: colon cancer (five patients), colon polyps (14 patients), ulcerative colitis
      (one patient), and hemorrhoids (22 patients). One small bowel tumor was detected
      at small bowel series. Concerning malignant lesions that were responsible for
      IDA, 22 malignant lesions were found in patients of 50 years or older, accounting
      for 16.8% (22 of 131 patients), while only one (1.3%) early gastric cancer was
      found in the younger patients. CONCLUSION: This study demonstrated that
      gastrointestinal blood loss is the main cause of IDA in adult men, and that there
      is a high rate of malignancy in men older than 50 years, emphasizing the need for
      a complete, rigorous gastrointestinal examination in this group of patients.
      Considering blood-letting cupping therapy, there is a need to consider culture
      specific procedures as a possible cause of IDA.

PMID- 21720056
TI  - Relationship between three-year survival and functional outcome at discharge from
      acute-care hospitals in each subtype of first-ever ischemic stroke patients.
AB  - BACKGROUND: We studied the relationship between survival prognosis and the
      functional outcome at discharge from acute-care hospitals in each subtype of
      ischemic stroke patients. METHODS: A total of 853 consecutive patients with first
      ever ischemic stroke, recruited from December 1999 to November 2002, were
      followed for 725.8 +/- 430.0 days. Functional outcome was scored using the
      modified Rankin scale (mRS). Survival analysis was performed using Kaplan-Meier
      curves, log rank test, and Cox regression model. RESULTS: The respective
      mortality of the groups with mRS scores of 0-2, 3, 4, and 5 were 13.1%, 25.0%,
      47.2% (p<0.05), and 74.0% (p<0.05) in cardioembolic infarction (CEI) patients;
      11.3%, 6.9%, 5.6%, and 46.7% (p<0.05) in atherothrombotic infarction (ATI)
      patients; 8.5%, 5.6%, 11.1%, and 0% (no patient) in lacunar infarction (LACI)
      patients; and 2.6%, 3.0%, 23.3% (p<0.05), and 28.9% (p<0.05) in infarction of
      unknown cause (IUC) patients. Multi-variate analysis showed that the mRS score
      was a significant predictive factor for death in CEI patients, and tended to be a
      predictive factor for death in ATI patients, or IUC patients. CONCLUSION:
      Functional outcome at discharge from acute-care hospitals may predict the
      survival prognosis of each subtype of ischemic stroke.

PMID- 21720057
TI  - Clinicoradiological profile and serum lipid levels of intracerebral hemorrhage in
      prior statin users.
AB  - OBJECTIVE: We aimed to evaluate whether serum lipid levels can influence the
      clinicoradiological recovery of intracerebral hemorrhage (ICH) in prior statin
      users. PATIENTS AND METHODS: Medical records were reviewed retrospectively in 381
      ICH patients (253 men and 128 women). Cardiovascular disease (CVD) risk factors,
      blood pressure at admission and the first in-hospital day, admission and 30-day
      scores of National Institute Health Stroke Scale (NIHSS) and modified Rankin
      scale (mRS), hematoma volume (HV), serum lipid levels were compared between prior
      statin users and non-users. RESULTS: Statins were pretreated in 56 patients (31
      men and 25 women). Statin users were older age, and had higher frequencies of
      dyslipidemia, diabetes mellitus, atrial fibrillation, prior stroke history and
      large HV compared to non-users. Serum levels of total cholesterol (TC) and low
      density lipoprotein cholesterol (LDL-C) were significantly decreased in the
      statin group compared to the non-statin group. There were no statistical
      differences in the other CVD risk factors, functional scores and other serum
      lipid levels between the two groups. HV was correlated inversely with serum
      levels of TC and LDL-C in both groups. Multiple logistic regression analysis
      showed that serum TC levels <=150 mg/dL were associated with statin use [Odds
      ratio (OR)=5.5, 95% confidence interval (CI)=1.55-19.58], worsening of NIHSS
      score (OR=1.4, 95% CI=1.21-1.63) and HV (OR=1.1, 95% CI=1.07-1.13) in ICH
      patients. A significant association was found between worsening of NIHSS score
      (OR=2.0, 95% CI=1.32-3.12) and worsening of mRS score (OR=3.3, 95% CI=1.33-8.00),
      HV (OR=1.3, 95% CI=1.01-1.76), and serum TC levels <=150 mg/dL in statin users.
      CONCLUSION: Prior statin users with serum TC levels <=150 mg/dL had worsening of
      outcome and HV. Excessive lowering of serum TC levels due to statin pretreatment
      may cause unfavorable clinicoradiological recovery of ICH. Physicians should
      monitor serum lipid levels carefully in statin users.

PMID- 21720058
TI  - Detection of bone lesions by CT in POEMS syndrome.
AB  - OBJECTIVE: To study the utility of CT for detection of small bone lesions in
      POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes)
      syndrome. For patients with a solitary bone lesion, irradiation is a first-line
      treatment, whereas systemic chemotherapy is indicated for patients with multiple
      bone lesions. Therefore it is important to correctly identify the number of bone
      lesions. METHODS: We studied the sensitivity of chest/abdomen/pelvic CT to detect
      bone lesions in 28 patients with POEMS syndrome. (99m)Tc-HMDP bone scintigraphy
      was performed in 14 patients, and the results were compared with CT. RESULTS: CT
      showed multiple bone lesions in 68% of the 28 patients, and 71% of the lesions
      had a diameter <10 mm. In 14 patients who underwent both CT and scintigraphy,
      bone lesions were detected in 57% by CT and in 79% by scintigraphy, but the
      location and nature of the identified lesions were considerably different; CT
      frequently showed small lesions (diameter <10 mm) in the vertebrae and pelvis,
      which were not detected by scintigraphy, whereas scintigraphy could show lesions
      in the skull and long bones. Overall, by using both examinations, multiple bone
      lesions were found for 86% of patients. CONCLUSION: CT is particularly useful to
      detect small bone lesions. CT and bone scintigraphy are complementary, and
      therefore both should be performed for bone survey in POEMS syndrome.

PMID- 21720059
TI  - Kinetics of serum beta-D-glucan after Pneumocystis pneumonia treatment in
      patients with AIDS.
AB  - OBJECTIVE: Serum beta-D-glucan has been demonstrated as a reliable, adjunct
      diagnostic marker for PCP, but its kinetics after PCP treatment are poorly
      understood. To evaluate the correlation between the levels of beta-D-glucan and
      the clinical response, we investigated the individual transition of serum beta-D
      glucan levels after the initiation of PCP treatment. METHODS: Retrospective study
      PATIENTS: Seventeen PCP patients with AIDS who were admitted to our hospital were
      analyzed. RESULTS: All subjects showed the serum beta-D-glucan levels above the
      cut-off value, and the median level was 224 pg/mL [IQR: 78-597] at the time of
      PCP diagnosis. There were no correlations between serum beta-D-glucan levels and
      CRP, LDH, or AaDO(2) at room air. Although there was a downward trend in serum
      beta-D-glucan level as PCP treatment was initiated, a significant number of
      subjects showed a marked increase in the serum beta-D-glucan levels despite their
      evident clinical improvement. CONCLUSION: The serum beta-D-glucan level does not
      reflect the severity and prognosis of PCP infection, and thus it may not be
      suitable for monitoring the response to treatment.

PMID- 21720060
TI  - Survey of patient and physician satisfaction regarding patient-centered
      outpatient consultations in Japan.
AB  - OBJECTIVE: The purpose of this study was to show the difference in consultation
      satisfaction between patient and physician in rural settings, and identify the
      variables affecting their satisfaction regarding these encounters. METHODS: We
      collected data by administering questionnaires that included questions regarding
      satisfaction for a patient-centered approach to patients and physicians,
      transcribing data from medical records, and observing consultations in person. We
      then modeled cumulative logits of patient and physician satisfaction scores by
      performing ordered logistic regression using the proportional odds model.
      PATIENTS: Seven physicians and 122 patients participated in the study. RESULTS:
      Both patients and physicians expressed high satisfaction with their consultation
      sessions. Patient satisfaction tended to be higher than physician satisfaction.
      Physicians were satisfied with longer consultations but patients were not.
      Moreover, the long waiting times dissatisfied patients. In cases of multiple
      healthcare episodes (courses of treatment for a different condition) during a
      single visit, patient satisfaction decreased, while physician satisfaction
      increased. Physician satisfaction for interactions in general was less when they
      checked the same patient who had previously visited them. CONCLUSION: Our
      findings suggest that if physicians feel satisfied with their consultation,
      patients also feel satisfied regardless of the physician's opinion. The variables
      that affect patient and physician satisfaction include prior visits with the same
      physician, consultation length, longer waiting times, and number of episodes.
      These findings from Japanese clinics are consistent with those previously
      reported for other countries.

PMID- 21720061
TI  - Rapid progression of hepatocellular carcinoma in a patient with autoimmune
      hepatitis.
AB  - We describe a case of a 69-year-old woman who developed rapidly progressive
      hepatocellular carcinoma (HCC) associated with autoimmune hepatitis (AIH) after a
      7-year follow-up. Markers for viral hepatitis were negative. Serum tumor markers
      including alpha-fetoprotein and prothrombin induced by vitamin K absence II rose
      suddenly, and a large tumor was detected in spite of regular surveillance for
      HCC. Surgical treatment was performed. The resected liver specimen revealed well
      to moderately differentiated HCC. Ki67 staining showed rapid proliferation of the
      HCC. Although the incidence of HCC in patients with AIH has been unclarified, the
      possible complication by HCC must not be overlooked.

PMID- 21720062
TI  - Criteria for early identification of aceruloplasminemia.
AB  - A 52-year-old Japanese woman being treated for type 1 diabetes showed
      forgetfulness and microcytic anemia with a high serum ferritin concentration.
      Serum and brain radiological examinations revealed aceruloplasminemia, which was
      confirmed by genetic testing. Aceruloplasminemia is characterized by the triad of
      retinal degeneration, diabetes mellitus, and adult-onset disorder of the
      extrapyramidal system. Though physicians should treat such patients earlier, it
      is difficult to diagnose the disease before the presentation of neurological
      symptoms. Despite the presence of microcytic anemia, aceruloplasminemia patients
      usually have a high serum ferritin concentration due to the complete absence of
      ceruloplasmin ferroxidase activity. Thus, physicians should consider
      aceruloplasminemia when diabetic patients present with microcytic anemia and a
      high serum ferritin concentration.

PMID- 21720063
TI  - Feminizing adrenocortical carcinoma with selective suppression of follicle
      stimulating hormone secretion and disorganized steroidogenesis: a case report and
      literature review.
AB  - We report a 61-year-old male with gynecomastia, poor libido and erectile
      dysfunction. Endocrinological studies showed high levels of estradiol and
      dehydroepiandrosterone sulfate. Although luteinizing hormone (LH) level was
      within the normal limit, the concentration of follicle-stimulating hormone (FSH)
      was under the normal limit. Delayed response of LH and poor response of FSH to
      gonadotropin-releasing hormone administration were detected. Magnetic resonance
      imaging of the abdomen revealed a left adrenal tumor. Although the surgically
      resected tumor was diagnosed as a high grade ACC based on Weiss's criteria of
      adrenocortical malignancy, no metastasis was detected. Since estrogen levels
      normalized after resection, feminizing ACC was confirmed. While LH concentration
      increased slightly after operation, FSH level became transiently elevated over
      the normal limit, and finally reached the normal range. These data may suggest
      that FSH was suppressed selectively by hormone produced by ACC different from
      estrogen.

PMID- 21720064
TI  - Top of the basilar syndrome in a young adult initially presenting with a
      convulsive seizure.
AB  - A 23-year-old man was admitted to our hospital due to loss of consciousness and a
      generalized convulsive seizure. He was diagnosed as having primary epilepsy and
      treated with antiepileptic drugs. Emergency CT scan of the head showed no
      abnormality. However, MRI scan of the head several days after admission revealed
      fresh infarctions caused by occlusion of the basilar artery, i.e., "top of the
      basilar" syndrome. This case indicates the need for precise differential
      diagnosis of convulsive seizure in an emergency situation. It should also be
      borne in mind that basilar occlusion with 'onset seizure' can occur even in young
      adults who have no risk factors for stroke.

PMID- 21720065
TI  - Three spinocerebellar ataxia type 2 siblings with ataxia, parkinsonism, and motor
      neuronopathy.
AB  - Spinocerebellar ataxia type 2 (SCA2) represents a family of dominant
      neurodegenerative disorders that results from CAG expansion repeat mutations. The
      phenotype consists of some common features, most notably progressive ataxia. We
      describe three siblings with SCA2, manifesting parkinsonism and ataxia in the
      first sibling, juvenile parkinsonism in the second and motor neuronopathy in the
      third. Genetic examination revealed expansion to 42, 43, and 42 CAG repeats.
      There was no relationship between the number of repeats and phenotype. The SCA2
      gene should be studied in families with heterogeneous neurodegenerative
      disorders, including motor neuron disease.

PMID- 21720066
TI  - Hepatocellular carcinoma in a case of Wilson's disease treated with
      radiofrequency ablation therapy.
AB  - A 37-year-old Japanese man was diagnosed with liver cirrhosis due to Wilson's
      disease in 2001 and treated with D-penicillamine. Thereafter, he was admitted to
      our hospital for further examination of a space occupying lesion in the liver.
      The patient was diagnosed with hepatocellular carcinoma (HCC) (7th segment, 2.5
      cm in diameter) in May 2010 and treated with radiofrequency ablation therapy.
      Biopsy findings from a non-cancerous area revealed a fatty liver, though
      cirrhotic nodules were not found. Long-term treatment for Wilson's disease may
      improve hepatic fibrosis, and careful screening for HCC by abdominal imaging is
      needed in such cases.

PMID- 21720067
TI  - A case of liver abscess caused by Edwardsiella tarda.
AB  - Edwardsiella tarda, a member of the Enterobacteriaceae family, is found in
      freshwater and marine environments. Extraintestinal infections of Edwardsiella
      tarda have been rarely reported. We describe a 70-year-old Japanese woman
      suffering from autoimmune hemolytic anemia, with liver abscess caused by
      Edwardsiella tarda. She had a history of cholecystectomy for gallbladder stone 10
      years prior to this admission. She was successfully treated with percutaneous
      transhepatic abscess aspiration and meropenem. This is the first report of liver
      abscess caused by Edwardsiella tarda in Japan.

PMID- 21720068
TI  - Adult Kawasaki disease.

PMID- 21720069
TI  - Bullous systemic lupus erythematosus.

PMID- 21720070
TI  - [Method of correcting sensitivity nonuniformity using gaussian distribution on
      3.0 Tesla abdominal MRI].
AB  - In the direction where the phased array coil used in parallel magnetic resonance
      imaging (MRI) is perpendicular to the arrangement, sensitivity falls
      significantly. Moreover, in a 3.0 tesla (3T) abdominal MRI, the quality of the
      image is reduced by changes in the relaxation time, reinforcement of the magnetic
      susceptibility effect, etc. In a 3T MRI, which has a high resonant frequency, the
      signal of the depths (central part) is reduced in the trunk part. SCIC, which is
      sensitivity correction processing, has inadequate correction processing, such as
      that edges are emphasized and the central part is corrected. Therefore, we used
      3T with a Gaussian distribution. The uneven compensation processing for
      sensitivity of an abdomen MR image was considered. The correction processing
      consisted of the following methods. 1) The center of gravity of the domain of the
      human body in an abdomen MR image was calculated. 2) The correction coefficient
      map was created from the center of gravity using the Gaussian distribution. 3)
      The sensitivity correction image was created from the correction coefficient map
      and the original picture image. Using the Gaussian correction to process the
      image, the uniformity calculated using the NEMA method was improved significantly
      compared to the original image of a phantom. In a visual evaluation by
      radiologists, the uniformity was improved significantly using the Gaussian
      correction processing. Because of the homogeneous improvement of the abdomen
      image taken using 3T MRI, the Gaussian correction processing is considered to be
      a very useful technique.

PMID- 21720071
TI  - [Analyses of restricted diffusion of water molecules using trabecular bone
      phantom].
AB  - We have reported that the apparent diffusion coefficient (ADC) was correlated
      with bone mineral density, but the relation between the restricted diffusion of
      the water molecules and the trabecular bone structure was unclear. The purpose of
      our study is to clarify this relationship using two component analyses with an
      original phantom. With an increase in the interspace area of the simulated
      trabecular bone, the ADC of the fast component was increased, and the fraction of
      the fast component was also increased. On the other hand, with an increase in the
      interspace area of the simulated trabecular bone, the ADC of the slow component
      was decreased, and the fraction of the slow component was increased. Moreover,
      the ADC and fraction of the dry vertebral bone agreed with those of the simulated
      trabecular bone. This result means that our phantoms can reproduce the actual
      trabecular bone structure, which induces the restricted diffusion. The diffusion
      of the water molecules was separated into fast and slow components because of the
      restricted diffusion of the trabecular bone structure. Our original phantom
      enables analyzing restricted diffusion, and this analytical method obtains more
      detailed information on trabecular bone structure.

PMID- 21720072
TI  - [Examination of motion artifacts for helical and non-helical scanning modes in
      head CT].
AB  - For head computed tomography (CT), non-helical scanning has been recommended even
      in the widely used multi-slice CT (MSCT). Also, an acute stroke imaging
      standardization group has recommended the non-helical mode in Japan. However, no
      detailed comparison has been reported for current MSCT with more than 16 slices.
      In this study, we compared the non-helical and helical modes for head CT,
      focusing on temporal resolution and motion artifacts. The temporal resolution was
      evaluated by using temporal sensitivity profiles (TSPs) measured using a temporal
      impulse method. In both modes, the TSPs and temporal modulation transfer factors
      (MTFs) were measured for various pitch factors using 64-slice CT (Aquilion 64,
      Toshiba). Two motion phantoms were scanned to evaluate motion artifacts, and then
      quantitative analyses for motion artifacts and helical artifacts were performed
      by measuring multiple regions of interest (ROIs) in the phantom images. In
      addition, the rates of artifact occurrence for retrospective clinical cases were
      compared. The temporal resolution increased as the pitch factor was increased.
      Remarkable streak artifacts appeared in the non-helical images of the motion
      phantom, in spite of the equivalent effective temporal resolution. In clinical
      analysis, results consistent with the phantom studies were shown. These results
      indicated that the low pitch helical mode would be effective for emergency head
      CT with patient movement.

PMID- 21720073
TI  - [Partial electrical reset of CT irradiation on implantable cardiac devices:
      relationship between reset and tube voltage, tube current, and rotation time].
AB  - The aim of this study was to investigate the relationship between partial
      electrical reset (PER) and CT scan parameters (tube voltage, tube current,
      rotation time, and product of tube current and rotation time in mAs). A cardiac
      resynchronization therapy pacemaker (Insync 8040, Medtronic Inc., Tokyo) and 320
      area detector CT scanner (Aquilion ONE, Toshiba medical systems, Otawara, Japan)
      with volume scan were used. The pacemaker was put in DDD mode. The PERs were
      interpreted using both the programmer's wave forms and error messages. The
      exposure was repeated 5 times per CT setting. The pacemaker was placed on the
      anterior wall and upper side of a chest phantom. Each CT scan was performed using
      the following parameters: tube voltage of 80, 100, 120, and 135 kV; tube current
      of 50-550 mA; and rotation time of 0.35-1.5 s. PERs were observed at 100, 120,
      and 135 kV, and more PERs were observed as the tube voltage increased. The PER
      tube current decreased as the rotation time was increased. In contrast, the PER
      tube current and rotation time product (mAs) increased as the rotation time was
      increased. More specifically, the radiation dose rate was the affected factor of
      the PERs. To avoid PER of pacemakers, CT scan parameters with lower radiation
      dose rates (low rather than high tube current and rotational time) is
      recommended. In conclusion, our results will help with CT scans of patients who
      have implantable cardiac devices (included pacemakers and cardioverter
      defibrillators).

PMID- 21720074
TI  - [Comparison of fat suppression techniques of bilateral breast dynamic sequence at
      3.0 T: utility of three-point DIXON technique].
AB  - The purposes of this study were to determine optimum flip angles (FAs) and to
      compare the effectiveness of fat suppression and signal homogeneity among three
      techniques, spectral attenuated with inversion recovery (SPAIR), principle of
      selective excitation technique (PROSET), and three-point DIXON technique (DIXON),
      of the bilateral breast dynamic sequence acquired using the optimum FA at 3.0 T.
      Using a homemade phantom that represented a tumor, fat, and a mammary gland, the
      optimum FAs were determined from the change of fat signal intensity, signal-to
      noise ratio (SNR) of the mammary gland, and contrast ratio (CR) between the tumor
      and mammary gland. The effectiveness of fat suppression and signal homogeneity
      were compared in ten breast cancer cases, using the CR between fat and pectoralis
      muscle signal intensities and the standard deviation (SD) of fat signal
      intensity, respectively. The optimum FAs for SPAIR, PROSET, and DIXON were 10,
      20, and 20 degrees, respectively. The mean CR between fat and pectoralis muscle
      signal intensities achieved using SPAIR, PROSET, and DIXON were 0.19, 0.30 and
      0.40, respectively, and the mean SDs of the fat signal intensities were 90.2,
      103.1, and 30.5, respectively. The DIXON technique provided better fat
      suppression and signal homogeneity than the other two techniques. The results of
      this study suggest the possible application of the DIXON technique in combination
      with the optimum FA setting as an effective fat suppression technique for the
      bilateral breast dynamic sequence at 3.0 T.

PMID- 21720075
TI  - [Appropriate cardiac phase for measurement of ADC of the brain using ECG
      triggered diffusion MRI].
AB  - Apparent diffusion coefficients (ADCs) are sometimes overestimated when they are
      measured in the brain near the basal ganglia because water molecules in brain
      tissues fluctuate with blood volume loading in the cranium. We determined
      detailed ADC changes during the cardiac cycle to evaluate the appropriate cardiac
      phases for accurate measurement of ADC values. Using 1.5 T MRI, we performed ECG
      triggered single-shot EPI to obtain ADC maps in each cardiac phase using
      techniques minimizing the bulk motion effect. The coefficient of variation (CV)
      of the ADC values during the cardiac cycle was over 50% near the basal ganglia.
      Moreover, the cardiac phase of the peak ADC value during the cardiac cycle was
      from 10 to 40% cardiac phases that follow systole. However, the CV of the ADC
      values of whole cardiac phases was higher than those with phases over 50% of the
      cardiac cycle near the basal ganglia because the effect of water fluctuation was
      almost eliminated. Therefore, accurate measurement of ADC values should be
      obtained from ADC maps of phases over 50% of the cardiac cycle.

PMID- 21720076
TI  - [Characteristics of TI scout image (look-locker) in the myocardial delayed
      enhancement MRI and the consistency of the null point between look-locker and IR
      T1TFE method].
AB  - Myocardial delayed enhancement imaging must regulate inversion time (TI) so that
      the signal intensity of the normal myocardium becomes null, and look-locker
      imaging is performed prior to myocardial delayed enhancement imaging to determine
      the optimal TI. We think that the null point measured by look-locker imaging may
      change with the adjustment of some imaging parameters like the IR-T(1)TFE
      sequence used in myocardial delayed enhancement imaging. Therefore, the purpose
      of this study is to examine the change of the null point with the adjustment of
      some imaging parameters for look-locker imaging and to study factors affecting
      the consistency of the null point with the IR-T(1)TFE sequence. The null point of
      both sequences of look-locker imaging and the IR-T(1)TFE sequence changed with
      the RR interval and with the number, FA, and interval of RF pulses applied within
      the RR interval. To match the null points in both sequences, it is necessary to
      make the RR intervals the same and to match the number, FA, and interval of RF
      pulses applied to within 1 heartbeat.

PMID- 21720077
TI  - [Experience of using a filmless system in dental practice at Hiroshima University
      Hospital, a former university dental hospital].
AB  - Our university hospital has had a policy of electronic patient recordkeeping,
      replacing paper-based recordkeeping, since September 1, 2008. Because the
      Department of Oral and Maxillofacial Radiology had already been using computed
      radiography for X-ray systems except for intraoral radiography and storing data
      in Digital Imaging and Communications in Medicine (DICOM) format, the following
      three conditions form the basis of the changes we made in relation to the
      introduction of this policy. We started 1. using imaging plates for intraoral
      radiography as well and storing the data in DICOM format; 2. diagnosed without
      the need for film; and 3. referred to past images displayed on the screen of our
      Radiology Information System (RIS). The introduction of digital intraoral
      radiography has many advantages: not only does it not require film and can all
      past images be referred to on the screen of the RIS, but radiation exposure times
      are also shorter, images can be saved electronically, and thus, film processing
      is redundant. The system improves efficiency and is also advantageous to patients
      and staff in other departments.

PMID- 21720078
TI  - [A preliminary study on measurement of muscle activity during mammography
      positioning].
AB  - This study focused on measuring examinees' muscle activities during mammography
      positioning using surface electromyography. Muscle activities were measured in
      three women (40-50s) in two-view mammography (MLO: mediolateral oblique, CC:
      craniocaudal). The muscles measured were the sternocleidomastoid, biceps,
      trapezius, and gastrocnemius, selected based on the visual analogue scale
      reported by Sharp et al. We used a multi-purpose portable bio-amplifier (Polymate
      AP1000) to assess the muscle activities. The results showed that the trapezius in
      right MLO and sternocleidomastoid in right CC were active in all three subjects.
      This suggests that the muscles directly related to mammography positioning are
      highly active. In addition, the gastrocnemius was active throughout the
      mammography. The biceps and gastrocnemius were also active in at least one of the
      three women. We believe that quantitative assessment of muscle activities during
      mammography positioning will contribute to the improvement of pain-reduction
      programs in mammography.

PMID- 21720079
TI  - [Research ethics and radiological protection: reflecting the discussion at the
      Japanese Society of Radiological Technology meeting].

PMID- 21720080
TI  - [Radiation-applied gauging in industry and its surroundings].

PMID- 21720082
TI  - [ Dosimetric principles and units].

PMID- 21720081
TI  - [For building the evaluation system of QA/QC for medical images].

PMID- 21720083
TI  - [Kanazawa University].

PMID- 21720084
TI  - [Statistical image analysis method to use for cerebral blood flow SPECT
      examination: difference and matters that require attention of processing of eZIS
      and iSSP].

PMID- 21720085
TI  - [Outline and activity of JIRA industry strategy planning office].

PMID- 21720086
TI  - Detection of atherosclerotic lesions in apolipoprotein E knockout mice using
      USPIO-enhanced magnetic resonance imaging.

PMID- 21720087
TI  - Development and maintenance of cancer stem cells under chronic inflammation.
AB  - In many human cancers, tumorigenic potential is not equally shared by all cells
      but is restricted to phenotypically distinct subpopulations termed cancer stem
      cells. Cancer stem cells are also capable of both self-renewal and
      differentiation, and these functional properties have been suggested to play
      major roles in tumor initiation and progression. The factors responsible for the
      development of cancer stem cells and their subsequent regulation are unclear, but
      several chronic inflammatory states have been associated with an increased risk
      of malignancy. Therefore, it is possible that specific processes associated with
      chronic inflammation, as well as the adaptation to cellular stress, regulate
      cancer stem cells. Several factors associated with chronic inflammation,
      including cytokines, oxidative stress, and hypoxia, induce the activation of
      specific cellular response programs that can affect the survival, proliferation,
      metabolism, and differentiation of cancer cells, as well as the self-renewal and
      quiescence of normal stem cells. In this review, we discuss how these adaptive
      processes potentially become subverted to enhance the development and function of
      cancer stem cells.

PMID- 21720088
TI  - Inhibition of nitric oxide synthase in hyperdynamic circulation of rats with
      early or late cirrhosis secondary to common bile duct ligation.
AB  - BACKGROUND/AIMS: Preventing internal hemorrhage extends the lifespan of rats with
      chronic bile duct ligation (CBDL), a common animal model of portal hypertension.
      We investigated hemodynamics during the early and late stages of cirrhosis caused
      by CBDL. We also evaluated the hemodynamic influence of NO, which is the chief
      vasodilator in hyperdynamic syndrome, by administration of an NO synthase
      inhibitor (N(G)-nitro-L-arginine methyl ester: L-NAME; 10 mg/kg).
      ANIMALS/METHODS: In 24 Sprague-Dawley rats (9 sham rats and 15 CBDL rats),
      hemodynamics were assessed under conscious and unrestrained conditions 4 and 8
      weeks after surgery. Before and 30 minutes after L-NAME administration, the
      cardiac index (CI) and regional blood flow were measured with the reference
      sample method using (141)Ce- and (113)Sn-microspheres (15 um in diameter).
      RESULTS: A hyperdynamic systemic circulation and splanchnic hyperemia were
      observed after CBDL, and these changes increased with the progression of
      cirrhosis. L-NAME significantly diminished the hyperdynamic circulation and also
      reduced splanchnic hyperemia. In 4-week CBDL rats, a low hemoglobin concentration
      made an important contribution to the hyperdynamic circulation, and the portal
      collateral system collapsed when inflow to the portal territory was reduced by L
      NAME treatment. In 8-week CBDL rats, systemic hemodynamics were closely linked to
      both the splanchnic circulation and the renal circulation before and after L-NAME
      administration, apart from hepatic artery blood flow. CONCLUSION: The distinctive
      hemodynamic changes of portal hypertension were found in 8-week CBDL rats. Thus,
      8-week CBDL rats may be a better animal model of human portal hypertension than 4
      week CBDL rats.

PMID- 21720089
TI  - Prognostic factors affecting clinical outcomes after coronary artery bypass
      surgery: analysis of patients with chronic kidney disease after 5.9 years of
      follow-up.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is a highly successful
      treatment for prolonging the lives of selected patients; however, preoperative
      and postoperative renal dysfunction has been an important predictor of adverse
      cardiovascular events. Concerns have recently grown regarding chronic kidney
      disease (CKD), which is an independent risk factor for cardiovascular diseases.
      In the present study we examined the significance of renal function on the basis
      of the estimated glomerular filtration rate (eGFR) and analyzed other factors as
      predictors of long-term clinical outcomes after CABG. METHODS: The subjects were
      195 patients who underwent CABG from July 1996 through September 2008 at our
      hospital. Patients who received preoperative dialysis or who died during
      hospitalization or both were excluded. The patients were divided into 2 groups
      based on eGFR at the time of discharge (eGFR >=60 mL/min/1.73 m(2): non-CKD
      group; or eGFR <60 mL/min/1.73 m(2): CKD group), and long-term outcomes were
      compared between the groups. The effects of other risk factors on long-term
      morbidity and mortality were also examined. RESULTS: The mean age of patients was
      64.6 +/- 9.3 years, and the mean duration of follow-up was 69.5 +/- 44.5 months.
      There were no significant differences in either deaths from all causes or
      cardiovascular deaths between the CKD group and the non-CKD group. Multivariate
      analysis using the Cox proportional hazards model revealed that age (hazard
      ratio, 1.044; p=0.001) was a predictor of all-cause death and that age (hazard
      ratio, 1.154; p<0.001), diabetes mellitus (hazard ratio, 3.122; p=0.046),
      unstable angina (hazard ratio, 5.012; p=0.003), and proteinuria (hazard ratio,
      7.982; p<0.001) were predictors of cardiovascular death. conclusions: Our study
      demonstrates that age, diabetes mellitus, unstable angina, and proteinuria are
      factors that affect long-term prognosis after CABG, whereas eGFR <60 mL/min/1.73
      m(2) is not a predictive risk factor for either all-cause death or cardiovascular
      death. Although the predictive value of eGFR <60 mL/min/1.73 m(2) is generally
      accepted, analysis of our own data with receiver operating characteristic curves
      shows that eGFR <50 mL/min/1.73 m(2) is a more sensitive predictor of long-term
      outcome.

PMID- 21720090
TI  - Electrophysiological and histological investigation on the gradual elongation of
      rabbit sciatic nerve.
AB  - A basic study using animal models was performed to investigate whether the
      sciatic nerve retains physiological functions and normal morphology after the
      gradual elongation associated with adjacent bone elongation. Electrophysiological
      and histological studies were performed on the elongated sciatic nerve of rabbit
      accompanied by the femur bone elongation. Compound action potentials evoked by
      electrical stimulation of the sciatic nerve were recorded and histological
      specimens of elongated nerve fibers were obtained immediately after final bone
      elongation from 4 rabbits (immediate group). Three rabbits were allowed to
      recover for 8 weeks after the bone elongation (maintained group). Three rabbits
      without bone elongation were used as controls of the immediate and maintained
      groups (control group). In the immediate group, the average amplitude of evoked
      nerve potentials were 30.38 +/- 1.58 mV before elongation and diminished
      significantly to 18.35 +/- 1.25 mV immediately after elongation (P<0.01). The
      amplitude of evoked potentials was not significantly different between before
      (30.30 +/- 0.61 mV) elongation and after elongation (27.47 +/- 1.63 mV) in the
      maintained group. The axonal area of the myelinated nerve fibers of the proximal
      region of the sciatic nerve in the immediate group was significantly decreased
      after elongation (P<0.01). The decrease in the area of the distal region was
      greatest in the control group and was followed by that in the maintained group
      and the immediate group (P<0.05, 0.01). These results suggest that the sciatic
      nerve shows dysfunction immediately after elongation, but can recover
      electrophysiologically and histologically several weeks after elongation.

PMID- 21720091
TI  - Study of T serotypes and Emm genotypes of Streptococcus pyogenes in children with
      pharyngitis and tonsillitis.
AB  - Streptococcus pyogenes, or group A Streptococcus (GAS), causes superficial
      infections of the upper respiratory tract that manifest as diseases such as
      pharyngitis and tonsillitis. T serotypes, emm genotypes, and the antimicrobial
      susceptibility of GAS isolated from the pharynges of patients with pharyngitis
      and tonsillitis were studied. The two most common T serotypes were T12 (10/25:
      40%) and T1 (7/25: 28%), and the two most common emm genotypes were emm12 (12/27:
      44%) and emm1 (7/27: 26%). Good correlation was observed between these T
      serotypes and emm genotypes.

PMID- 21720092
TI  - Long-lasting narrowing of the parent artery after bilateral clipping of mirror
      image aneurysms of distal anterior cerebral arteries: a case report.
AB  - Because multiple intracranial aneurysms are not rare, accurate preoperative
      detection of asymptomatic aneurysms is important. In this paper, we report a
      ruptured distal anterior cerebral artery (DACA) aneurysm associated with an
      unruptured mirror-image aneurysm in a 62-year-old man presenting with headache.
      Although delayed vasospasm after subarachnoid hemorrhage has been reported to
      persist for 2 to 3 weeks, angiographic parent artery narrowing was far more
      prolonged in our case. Computed tomography revealed a subarachnoid hemorrhage in
      the interhemispheric and right sylvian fissures and a right frontal lobe
      hematoma. Digital subtraction angiography demonstrated bilateral symmetric
      saccular aneurysms of DACAs. On the day of admission, both aneurysms were clipped
      using an interhemispheric approach in a one-stage procedure, and the hematoma was
      aspirated. Angiography performed 8 days after the surgery demonstrated a residual
      aneurysm neck on the left side. Follow-up digital subtraction angiography
      performed on day 42 from onset showed resolution of the residual aneurysm neck
      along with narrowing of the left A2. However, at 7 months, the A2 narrowing had
      lessened. The location of the bilateral aneurysms near the midline facilitated a
      single approach but necessitated the application of juxtaposed clips. Regarding
      the pathogenesis of the bilateral aneurysms, previous reports have suggested
      symmetry of congenital anatomic defects and hemodynamic stress as potential
      causes. The persistent narrowing that was observed could have resulted from
      proliferative vasculopathy or from fibrosis possibly induced by the clips.

PMID- 21720093
TI  - Permanent bilateral cortical blindness due to reversible posterior
      leukoencephalopathy syndrome.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is induced by acute
      cerebral edema. Its symptoms include seizures, headache, altered mental status,
      and visual disturbances. The clinical and radiological findings are usually
      transient. This report describes a case of RPLS resulting in bilateral total
      blindness. A 40-year-old man presented with lethargy and bilateral visual loss.
      He had a 20-year history of hypertension, but had never been treated. On
      presentation, the left eye was able to perceive light, but the right eye was not.
      Radiological examination showed diffuse edema in the brain, and ocular fundus
      examination revealed severe bilateral hypertensive retinopathy. Antihypertensive
      therapy improved the patient's general condition, including blood pressure.
      Radiological findings 5 months later showed resolution of most of the abnormal
      signal areas. However, total blindness had developed in both eyes by day 15, and
      two courses of pulsed corticosteroid therapy failed to restore the visual loss.

PMID- 21720094
TI  - Migration of a fish bone into the right renal vein.
AB  - We describe a patient in whom a fish bone penetrated the duodenum and migrated
      into the right renal vein. The bone was successfully removed with surgery. The 75
      year-old man was admitted to Nippon Medical School Tama Nagayama Hospital because
      of right upper abdominal pain persisting for 7 days. The patient's medical
      history was not relevant to the current disorder. Plain radiography showed no
      abnormalities. Computed tomography revealed a linear object of high intensity
      that had penetrated the duodenum and migrated into the right renal vein with
      thrombus. The object was surrounded by a low-density area, suggesting severe
      inflammation. The patient had eaten fish 1 day before the onset of abdominal
      pain. We diagnosed duodenal penetration caused by an ingested fish bone.
      Endoscopic examination showed erosion, but no fish bone or ulceration was
      detected in the duodenum. The patient was treated conservatively with fasting,
      peripheral parental nutrition, and intravenous antibiotics. Three days after
      admission, non-contrast-enhanced computed tomography showed no movement of the
      foreign body. The patient continued to have pain, and the decision was made to
      surgically explore the abdomen. Intraoperative ultrasonography showed that the
      foreign body had migrated completely into the right renal vein with thrombus.
      Severe inflammation of the right renal vein was observed. Because we could not
      remove the foreign body without seriously injuring the right renal vein, right
      nephrectomy was performed. Macroscopic examination of the surgical specimen
      confirmed the presence of a fish bone with thrombus in the right renal vein. The
      patient was discharged 9 days after operation, with no complications.

PMID- 21720095
TI  - A case of xanthogranulomatous cholecystitis preoperatively diagnosed with
      contrast-enhanced ultrasonography.
AB  - We report a case of xanthogranulomatous cholecystitis (XGC) that was diagnosed
      preoperatively by means of ultrasonography (US) with the contrast-enhancement
      agent Sonazoid after a false-positive result had been obtained with fluorine-18
      fluorodeoxyglucose positron emission tomography (FDG-PET). A 69-year-old woman
      was admitted because of right upper quadrant pain. Blood tests revealed a serum
      CA19-9 level of 749.8 IU/L. Computed tomography (CT), US, and magnetic resonance
      imaging of the abdomen showed abnormal thickening of the gallbladder wall but no
      stones. The border between the gallbladder and the liver was unclear. FDG-PET
      revealed a lesion with increased uptake of tracer in the gallbladder wall. The
      thickness of the lesion was similar to that on CT. We suspected gallbladder
      carcinoma with hepatic invasion. To confirm the tentative diagnosis, we performed
      US with the contrast-enhancement agent Sonazoid. The gallbladder wall was
      homogeneously enhanced in the early vascular phase and remained enhanced for 90
      seconds. Enhancement of the gallbladder wall was smooth and regular. The border
      between the gallbladder and liver was clear and smooth. On the basis of these
      examinations, we diagnosed chronic cholecystitis (XGC suspected), not gallbladder
      carcinoma. At surgery, the gallbladder wall was observed to be extremely thick
      because of severe inflammation, and cholecystectomy was performed. XGC was
      diagnosed on intraoperative pathological examination. Histopathological
      examination showed XGC, severe proliferative fibrosis with formation of multiple
      yellow-brown intramural nodules, and foamy histiocytes without malignant cells.
      In conclusion, the present case of XGC was diagnosed preoperatively with contrast
      enhanced US after a false-positive result had been obtained with FDG-PET.
      Contrast-enhanced US can thus play important roles in diagnosing gallbladder
      disease and selecting treatment.

PMID- 21720096
TI  - Esophageal stripping creates a clear operative field for lymph node dissection
      along the left recurrent laryngeal nerve in prone video-assisted thoracoscopic
      surgery.
AB  - We describe a 54-year-old man in whom esophageal carcinoma was diagnosed and who
      underwent video-assisted thoracoscopic surgery of the esophagus (VATS-E) in the
      prone position. Initially, the patient was fixed in a semiprone position, from
      which he could be rotated to a prone or left lateral position. Four ports were
      inserted, and then the patient was rotated to the prone position. Once the
      patient was prone, gravity caused the lung to move downwards. Next, the chest
      cavity was inflated with a CO(2) insufflation pressure of 6 mm Hg. Esophagectomy
      was then performed, and the lymph nodes in the middle and lower mediastinum and
      along the right recurrent laryngeal nerve were dissected. In the left upper
      mediastinum, lymph node dissection was performed after the residual esophagus was
      stripped. Stripping of the residual esophagus created sufficient working space
      and a clear operative field for lymph node dissection. VATS-E in the prone
      position has achieved remarkable results in Japan. It allows a clear operative
      view of the middle and lower mediastinum, but the working space in the upper
      mediastinum is limited. Our results indicate that esophageal stripping in prone
      VATS-E allows for safe and straightforward lymph node dissection along the left
      recurrent laryngeal nerve. Our technique overcame the difficulties usually
      encountered with this type of lymph node dissection.

PMID- 21720097
TI  - Possible underlying influence of p38MAPK and NF-kappaB in the diminished anti
      anxiety effect of diazepam in stressed mice.
AB  - The present study was designed to explore the possible nitriergic influence and
      role of p38MAPK and NF-kappaB in the diminished anti-anxiety effect of diazepam
      in stressed mice, using the elevated plus maze and light/dark box to assess
      anxiety. Immobilization stress for 6 h enhanced an anxiety-like behavior and
      increased plasma nitrite levels in mice. Diazepam (2 mg/kg, i.p.) produced an
      anti-anxiety effect in unstressed mice, but could not produce any change in
      anxiety levels of stressed mice. SB-203580 (2 mg/kg, i.p.), a specific inhibitor
      of p38MAPK, per se produced a significant antianxiety-like activity in stressed
      mice. Administration of a combination of SB-203580 (2 mg/kg, i.p.) and diazepam
      (2 mg/kg) in stressed mice produced a significantly higher antianxiety-like
      activity than that produced by SB-203580 alone. Pyrrolidine dithiocarbamate
      (PDTC), an inhibitor of the activation of NF-kappaB, per se produced a
      significant antianxiety-like activity in stressed mice. Combination of PDTC and
      diazepam also served to produce a higher significant antianxiety-like activity in
      stressed mice than that produced by PDTC alone. Diazepam could not produce any
      change in plasma nitrite levels in both unstressed and stressed mice. Both SB
      203580 (2 mg/kg, i.p.) and PDTC (100 mg/kg, i.p.) significantly decreased plasma
      nitrite levels in stressed mice. The observations indicate that the diminished
      anti-anxiety effect of diazepam in stressed mice may involve strong nitriergic
      influence and may further be p38MAPK- and NF-kappaB-dependent.

PMID- 21720098
TI  - Production of mouse fibroblast growth factor 4 in E. coli and its application for
      isolation and maintenance of mouse trophoblast stem cells in vitro.
AB  - Fibroblast growth factor 4 (FGF4) promotes isolation of trophoblast stem (TS)
      cells from mouse blastocysts and maintenance of TS cells in an undifferentiated
      state in vitro. To date, commercially available, bacterially expressed human FGF4
      (RhFGF4) has been used generally for this purpose. In this study, HismFGF4, a 6x
      histidine-tagged mouse FGF4, was produced in E. coli and purified using heparin
      column chromatography. We demonstrated that HismFGF4 (25 ng/ml) more efficiently
      generates mouse TS cells from a single blastocyst than RhFGF4 (25 ng/ml) and that
      TS cells isolated and maintained with HismFGF4 retained their ability to
      differentiate into the trophoblast cell lineage in vitro. In addition, TS cells
      cultured with HismFGF4 (25 ng/ml) were maintained in an undifferentiated state
      better than with RhFGF4 (25 ng/ml). To the best of our knowledge, this is the
      first application of a mouse FGF4 derivative for isolation and maintenance of
      mouse TS cells.

PMID- 21720099
TI  - [Cancer immunotherapy by utilizing dedritic cells derived from pluripotent stem
      cells].
AB  - It was recently revealed that ES-cell like pluripotent stem cells, designated as
      iPS cells, can be generated from somatic cells. iPS cells could be used as not
      only a source of regeneration medicine, but also a source of cell vaccine.
      Pluripotent stem cells are characterized by pluripotency and infinite propagation
      capacity. Non-virus-mediated methods for gene transfer have been established.
      Genetic modification of pluripotent stem cells and subsequent in vitro
      differentiation to dendritic cells would be an attractive strategy. Here we
      describe the previous studies about cancer immunotherapy by utilizing dendritic
      cells derived from pluripotent stem cells.

PMID- 21720100
TI  - [Chlamydia-associated arthritis and enteropathic arthritis--two important
      spondyloarthritides].
AB  - Spondyloarthritis (SpA) includes reactive arthritis (ReA) and enteropathic
      arthritis (EA), which are clinically important but often misdiagnosed. ReA,
      sterile inflammatory arthritis, arises after certain genitourinary or
      gastrointestinal infections. Chlamydia are the most common pathogens causing ReA;
      ReA due to Chlamydia infection is called Chlamydia-associated arthritis (Chl-AA).
      Recently, Chlamydia trachomatis was detected in the synovial tissue from patients
      with ReA by electronmicroscopy. In addition, mRNA as well as DNA has been
      detected in the synovial tissue, suggesting that Chlamydia are viable in inflamed
      joints. Thus, the notion that ReA is a sterile inflammation should be
      reconsidered. Chl-AA patients, especially women, often show no symptoms and signs
      of genitourinary infection. Thus, Chl-AA should be suspected in patients with
      inflammatory arthritides that is difficult to diagnose. EA is accompanied by
      inflammatory bowel diseases (IBD). In Japan, over 130,000 individuals have IBD;
      IBD is diagnosed in 6,500 individuals every year. Around 10% IBD patients develop
      arthritis, suggesting that 13,000 patients develop arthritis every year. SpA
      includes peripheral and axial arthritis; axial arthritis includes spondylitis and
      sacroiliac arthritis. Sacroiliac joint tests need to be performed to diagnose
      sacroiliac arthritis. Rheumatologists should be aware of the pathogenesis of Chl
      AA and EA and diagnose and treat these diseases appropriately.

PMID- 21720101
TI  - [Role of histone modifications in differentiation and effector function of CD8 T
      cells: update review including genome-wide analysis].
AB  - Evidence including genome-wide analyses have uncovered that epigenetic mechanisms
      regulate differentiation and effector functions in CD8 T cells. Gene expression
      profiles change when CD8 T cells differentiate from naive T cells to memory T
      cells. It has been shown that this programmed differentiation is regulated by
      epigenetic mechanisms. Upon antigen stimulation, CD8 T cells activate and acquire
      effector functions to target cells. Effector molecule gene expressions are
      upregulated by epigenetic mechanisms in CD8 T cells. It is suggested that memory
      T cells respond more rapidly to antigens because chromatin structures of effector
      molecule genes are open and their gene transcriptions are poised for activation.

PMID- 21720102
TI  - [Mechanisms and therapeutics of glucocorticoid-induced osteoporosis].
AB  - Mechanisms of glucocorticoid-induced osteoporosis (GIOP) are categorized into
      local and systemic effects. In the local mechanisms, direct inhibitory effect of
      glucocorticoid on bone formation is thought to be one of the important mechanisms
      of GIOP. In contrast, secondary hyperparathyroidism induced by negative balance
      of calcium due to inhibition of absorption and increase of excretion is an
      important systemic mechanism of GIOP. Other mechanisms of GIOP are also shown in
      this review. From clinical points of view, serum markers for evaluation of GIOP
      have been discussed. Osteocalcin, procollagen type I N-terminal peptide, and bone
      specific alkaline phosphatase as markers of bone formation are decreased in GIOP.
      Collagen I N-terminal telopeptide and tartrate resistent acid phosphatase isoform
      5b as markers of bone resorption are increased in GIOP. Clinical guidelines have
      recommended that bisphosphonate is the first choice for the treatment of GIOP.
      Teriparatide is recombinant human parathyroid hormone 1-34, which should be
      considered as a therapeutic option for those at high risk of bone fracture.
      Denosumab, an anti receptor activator of nuclear factor-beta ligand approved as a
      drug for postmenopausal osteoporosis was also effective for GIOP in clinical
      trials.

PMID- 21720103
TI  - [Efficacy and safety of combination therapy with mizoribine and methotrexate for
      rheumatoid arthritis resistant with methotrexate].
AB  - Background. MZB is a purine analog, and is used as a disease modifying anti
      rheumatic drug (DMARD). We conducted an open label uncontrolled clinical trial to
      evaluate the efficacy and safety of combination therapy with methotrexate (MTX)
      and mizoribine (MZB). Methods. Thirty one RA patients (9 males, 22 females, 68+/
      12 year-old) who fulfilled ACR criteria of RA and did not show sufficient
      clinical response to MTX were included. MZB (150 mg/day, once a day) were added
      to MTX. DAS28-CRP was measured at day 0 and 1, 3, 6, and 12 months after the
      treatment. Adverse events were recorded. Results. Overall DAS28-CRP was
      significantly decreased from 4.4+/-1.0 to 3.1+/-1.3 at 3 months (p<0.01), 2.7+/
      0.68 at 6 months (p<0.01), 2.4+/-1.4 at 12 months (p<0.01). Seventeen patients
      (55%) achieved significant improvement of DAS28-CRP. Number of swollen joints of
      responders before the treatment was significantly fewer than that of non
      responders. Improvement of DAS28-CRP was significantly different between the
      responders (0.91+/-0.74) and non-responders (0.18+/-0.66) at 1 month (p<0.01).
      Nine patients (29%) could achieve remission Four patients experienced adverse
      events. Conclusions. MTX and MZB combination therapy was effective and relatively
      safety.

PMID- 21720104
TI  - [Case of microscopic polyangiitis and giant cell arteritis after influenza
      vaccination].
AB  - We report a case of microscopic polyangiitis (mPA) and giant cell arteritis (GCA)
      (polyangiitis overlap syndrome) after influenza vaccination. A 67-year-old female
      with chronic kidney disease, who had been observed by a physician, presented
      fever and headache after immunization of influenza vaccine. She was diagnosed as
      having with mPA and GCA based on symptoms, worsening of renal function, biopsy of
      temporal artery (giant cell arteritis) and skin (microscopic polyangiitis),
      pulmonary involvement and the presence of myeloperoxidase-specific anti
      neutrophil cytoplasmic antibodies (MPO-ANCA). She was treated with prednisolone
      (PSL) and the symptoms were improved. However, two months later she was presented
      with general physical weariness. She was diagnosed as having with pneumocystis
      pneumonia, cytomegalovirus infection and cryptococcosis. Despite intensive
      treatment, she was died and autopsy was performed. The present case suggests that
      the influenza vaccination may cause different types of vasculitis, mPA and GCA,
      through the common mechanism in pathophysiology. This patient is also the first
      case of mPA and GCA proven by histological examination.

PMID- 21720105
TI  - [Microscopic polyangiitis with renal mass-like lesion: a case report].
AB  - A 63-year-old man was admitted to our hospital because of persistent fever,
      weight loss, painful foot, and purpura on his extremities. He had lower extremity
      peripheral neuropathy, and skin biopsy of the purpura revealed vasculitis. Serum
      tests for myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA),
      proteinase 3-ANCA, and ANCA (indirect fluorescent antibody method) were all
      negative. Computed tomography revealed a 6-cm large, irregularly shaped lesion in
      the right kidney, while the nasal sinuses and lungs were intact. Based on these
      findings, a diagnosis of suspected systemic vasculitis associated with renal cell
      carcinoma was made. Thus, right nephrectomy was performed. However, the
      pathological findings showed a large infarct with necrotizing vasculitis of the
      arcuate, interlobular, and perinephric small arteries and a crescent formation in
      the glomerulus. Based on these findings, he was diagnosed with microscopic
      polyangiitis. Due to rapidly worsening symptoms of purpura and neuropathy,
      treatment with a high dose of corticosteroid was initiated on postoperative day
      2, which led to improvement of his symptoms. Vasculitis accompanied with a mass
      like lesion is occasionally confused with malignancy. The lesion in our patient
      was considered to have originated by asymptomatic renal infarction. This case
      suggests that a renal mass-like lesion with vasculitis should be diagnosed with
      care.

PMID- 21720106
TI  - Expression of cyclooxygenase-2 in the endometrium of gilts with different stages
      of endometritis.
AB  - The present study determined the association among the expression of COX-2,
      stages of endometritis, and types and number of local immune cells infiltrating
      into the gilts' endometrium. The uterine tissues from 24 Landrace x Yorkshire
      gilts identified as acute endometritis (n = 7), chronic endometritis (n = 7), and
      normal endometrium (n = 10) were included. The tissues were prepared for both
      histological and immunohistochemical investigations. The immunoexpression of COX
      2 in every layer of the gilts' endometria was appraised by avidin-biotin
      peroxidase complex method via image analysis; and was reported as percentage of
      positive area and staining index. The results revealed that the immunoexpression
      of COX-2 was found only in the surface epithelial layer. The gilts with acute
      endometritis possessed higher both percentage of positive area (68.99% versus
      4.50% and 3.43%, P < 0.001) and staining index (1.13 versus 0.05 and 0.04, P <
      0.001) than those with chronic endometritis and normal endometrium, respectively.
      Positive correlations between the number of surface epithelial neutrophils and
      percentage of COX-2 positive area (r = 0.47, P = 0.022), as well as mean staining
      index (r = 0.44, P = 0.032) were observed. In conclusion, the immunoexpression of
      COX-2 was found strongest in the gilts with acute endometritis, meanwhile it was
      not different between those with chronic endometritis and normal endometrium.
      This suggested that the expression of COX-2 might be dependent not only on the
      infiltration of local immune cells in the endometrium, but also on the duration
      of exposure with inflammatory agents.

PMID- 21720107
TI  - Possible drug-induced hepatopathy in a dog receiving zonisamide monotherapy for
      treatment of cryptogenic epilepsy.
AB  - A 9-year old female spayed Rottweiler was diagnosed with cryptogenic epilepsy and
      started on zonisamide monotherapy (8.3 mg/kg, PO, q 12 hr). Three weeks after the
      1st dose of zonisamide the dog presented for vomiting, inappetence and icterus.
      Serum biochemistry showed marked elevation of liver enzymes, consistent with
      hepatocellular damage and cholestasis. No underlying cause for liver disease was
      identified and a drug-induced hepatopathy was suspected. Zonisamide was
      discontinued and replaced by potassium bromide. Supportive therapy consisted of
      intravenous fluids, antiemetics, antibiotics and hepatoprotectants. The dog made
      a complete recovery and serial serum biochemical examinations showed complete
      normalisation of liver parameters 8 weeks after discontinuation of zonisamide.
      Based on a human Drug-induced Liver Injury Diagnostic Scale, the likelihood for
      zonisamide-induced hepatopathy was classified as "possible". Veterinary
      practitioners and owners should be educated about the potential for an
      idiosyncratic drug reaction to zonisamide. If signs of hepatotoxicity are
      recognised early and zonisamide is discontinued, complete recovery is possible.

PMID- 21720108
TI  - Appropriate timing of proton MR spectroscopy in breast cancer.
AB  - Proton magnetic resonance (MR) spectroscopy (MRS) of the mammary gland region has
      customarily been used in basic research but is now commonly performed in clinical
      practice as MR techniques have improved. To debate its usefulness in a variety of
      fields and ultimately grade the timing of its use, a symposium entitled "Clinical
      Application and the Latest Technology of MRS-Timing of the Addition of MRS" was
      presented in 2009 at the 37th Annual Meeting of the Japanese Society for Magnetic
      Resonance in Medicine (JSMRM). MRS timing was classified into 3 grades according
      to when its addition: is always better, Grade 1; will sometimes be effective,
      Grade 2; and can provide only supplemental information, Grade 3. We describe the
      content of the meeting session on "Timing of the Addition of MRS in the Breast
      Cancer Field," explain the reasons for the timing classifications, and review
      previous papers.

PMID- 21720109
TI  - Discrepancy in T1 and T2 shortening of the globus pallidus in hepatic
      insufficiency: evaluation by susceptibility-weighted imaging.
AB  - PURPOSE: We assessed the signal of the globus pallidus (GP) in cases of hepatic
      insufficiency, especially to evaluate the degree of discrepancy in paramagnetic
      effects on shortening of T(1) and T(2)* using susceptibility-weighted images
      (SWI). MATERIALS AND METHODS: Seven patients with hepatic insufficiency underwent
      magnetic resonance (MR) examinations that included T(1)-weighted images (T(1)WI),
      T(2)-weighted images (T(2)WI), and SWI on a 1.5-tesla MR imager, and we compared
      their results to those of controls. On T(1)WI and T(2)WI, we measured signal
      intensity in the GP and posterior segment of the putamen (Put) to obtain a signal
      ratio (GP/Put ratio), and on SWI, we classified signal intensity into 4 grades:
      A, higher than the cortex; B, lower than the cortex and higher than the
      cerebrospinal fluid (CSF); C, lower than the CSF and higher than the red nucleus;
      and D, lower than the red nucleus. RESULTS: In the 7 patients with hepatic
      insufficiency, the mean GP/Put ratio was significantly higher on T(1)WI and
      T(2)WI than those values in controls. On SWI, we classified 2 cases each as Grade
      A, Grade B, and Grade C, and one as Grade D. Although the signal of the GP was
      elevated on T(1)WI, there was no decrease in signal on T(2)WI. On SWI, we
      obtained no low signal intensity. CONCLUSION: In patients with hepatic
      insufficiency, the globus pallidus did not show low signal intensity on either
      T(2)WI or SWI. Hyperintensity of the GP on T(1)WI without hypointensity on
      T(2)WI, or even SWI, suggests a discrepancy between paramagnetic effect on T(1)
      and T(2) shortening that reflects the accumulation of manganese and the presence
      of hepatic insufficiency.

PMID- 21720110
TI  - T2 mapping of muscle activity using ultrafast imaging.
AB  - Measuring exercise-induced muscle activity is essential in sports medicine.
      Previous studies proposed measuring transverse relaxation time (T(2)) using
      muscle functional magnetic resonance imaging (mfMRI) to map muscle activity.
      However, mfMRI uses a spin-echo (SE) sequence that requires several minutes for
      acquisition. We evaluated the feasibility of T(2) mapping of muscle activity
      using ultrafast imaging, called fast-acquired mfMRI (fast-mfMRI), to reduce image
      acquisition time. The current method uses 2 pulse sequences, spin-echo echo
      planar imaging (SE-EPI) and true fast imaging with steady precession (TrueFISP).
      SE-EPI images are used to calculate T(2), and TrueFISP images are used to obtain
      morphological information. The functional image is produced by subtracting the
      image of muscle activity obtained using T(2) at rest from that produced after
      exercise. Final fast-mfMRI images are produced by fusing the functional images
      with the morphologic images. Ten subjects repeated ankle plantar flexion 200
      times. In the fused images, the areas of activated muscle in the fast-mfMRI and
      SE-EPI images were identical. The geometric location of the fast-mfMRI did not
      differ between the morphologic and functional images. Morphological and
      functional information from fast-mfMRI can be applied to the human trunk, which
      requires limited scan duration. The difference obtained by subtracting T(2) at
      rest from T(2) after exercise can be used as a functional image of muscle
      activity.

PMID- 21720111
TI  - Time-resolved three-dimensional magnetic resonance velocity mapping of chronic
      thoracic aortic dissection: a preliminary investigation.
AB  - PURPOSE: The blood flow patterns of chronic thoracic aortic dissection are
      complicated, and their clinical significance remains unknown. We evaluated the
      technical and clinical potentials of time-resolved 3-dimensional (3D) magnetic
      resonance (MR) velocity mapping for assessing these patterns. METHODS: We used
      data collected from time-resolved 3D phase-contrast MR imaging of 16 patients
      with chronic thoracic aortic dissection to generate time-resolved 3D MR velocity
      mapping that included 3D streamline and path line. We investigated blood flow
      patterns of this disease in the mapping and compared them with the morphological
      changes of the patent false lumen. RESULTS: Time-resolved 3D MR velocity mapping
      visualized rapid flow at the entry and in the true lumen immediately distal to
      the entry. We observed slower helical or laminar flow in the patent false lumen.
      In patients with disease progression, slower helical flow following rapid entry
      jet collided with the outer wall of the false lumen and was also observed in a
      growing ulcer-like projection. CONCLUSION: We showed the potential of time
      resolved 3D MR velocity mapping for visualizing pathologic flow patterns related
      to chronic thoracic aortic dissection.

PMID- 21720112
TI  - Visualization of endolymphatic hydrops after intratympanic injection of Gd-DTPA:
      comparison of 2D and 3D real inversion recovery imaging.
AB  - PURPOSE: Endolymphatic hydrops of Meniere's disease has been visualized after
      intratympanic injection of gadopentetate dimeglumine (Gd-DTPA) using a 3
      dimensional (3D) inversion-recovery sequence with real reconstruction (3D real
      IR). This technique enables differentiation of bone and endo- and perilymph space
      on a single image but requires 15 min of scan time. Therefore, we compared it
      with 2D real IR, which is faster. MATERIALS AND METHODS: We investigated 10 ears
      in 9 patients with suspected Meniere's disease. Twenty-four hours after
      intratympanic administration of 8-fold diluted Gd-DTPA, we obtained 3D and 2D
      real IR images as well as magnetic resonance (MR) cisternography at 3 tesla.
      Three radiologists independently graded the degree of endolymphatic hydrops
      according to previously proposed criteria. Contrast-to-noise ratio (CNR) between
      peri- and endolymph was measured. RESULTS: We could evaluate the degree of
      endolymphatic hydrops in 9 cochleas and 10 vestibules but not in a tenth cochlea,
      which was too faintly enhanced on both 2D and 3D real IR. Grading of all
      evaluated cochleas and vestibules agreed completely among the 3 radiologists.
      Evaluation on 2D real IR and 3D real IR also agreed completely. Mean CNR was
      significantly higher on 3D than 2D real IR (P<0.05), and CNR on both correlated
      significantly (r = 0.872). CONCLUSION: Endolymphatic hydrops in Meniere's disease
      can be evaluated with 2D as well as 3D real IR and in a shorter scan time.

PMID- 21720113
TI  - Statistical parametric mapping for effects of verapamil on olfactory connections
      of rat brain in vivo using manganese-enhanced MR imaging.
AB  - PURPOSE: We investigated the effect of verapamil on the transport of manganese in
      the olfactory connections of rat brains in vivo using statistical parametric
      mapping and manganese-enhanced magnetic resonance (MR) imaging. METHODS: We
      divided 12 7-week-old male Sprague-Dawley rats into 2 groups of six and injected
      10 MUL of saline into the right nasal cavities of the first group and 10 MUL of
      verapamil (2.5 mg/mL) into the other group. Twenty minutes after the initial
      injection, we injected 10 MUL of MnCl(2) (1 mol/L) into the right nasal cavities
      of both groups. We obtained serial T(1)-weighted MR images before administering
      the verapamil or saline and at 0.5, one, 24, 48, and 72 hours and 7 days after
      administering the MnCl(2), spatially normalized the MR images on the rat brain
      atlas, and analyzed the data using voxel-based statistical comparison. RESULTS:
      Statistical parametric maps demonstrated the transport of manganese. Manganese
      ions created significant enhancement (t-score = 36.6) 24 hours after MnCl(2)
      administration in the group administered saline but not at the same time point in
      the group receiving verapamil. The extent of significantly enhanced regions
      peaked at 72 hours in both groups and both sides of the brain. The peak of extent
      in the right side brain in the group injected with saline was 70.2 mm(3) and in
      the group with verapamil, 92.4 mm(3). The extents in the left side were 64.0
      mm(3) for the group with saline and 53.2 mm(3) for the group with verapamil.
      CONCLUSION: We applied statistical parametric mapping using manganese-enhanced MR
      imaging to demonstrate in vivo the transport of manganese in the olfactory
      connections of rat brains with and without verapamil and found that verapamil did
      affect this transport.

PMID- 21720114
TI  - Acquisition parameters for diffusion tensor imaging to emphasize fractional
      anisotropy: phantom study.
AB  - Diffusion tensor imaging (DTI) is a magnetic resonance (MR) imaging technique
      that has attracted attention in recent years for applications such as nerve fiber
      tracking, neurography, and tumor detection. In DTI measurements, 2 motion-probing
      gradient (MPG) pulses are applied to evaluate water diffusion. In DTI for nerve
      fiber tracking, acquisition parameters, such as strength, duration, and
      separation of MPGs, influence the MR signal. In this study, we set acquisition
      parameters in DTI to emphasize fractional anisotropy to clarify the direction of
      nerve fibers. We performed Monte Carlo simulations of restricted diffusion in a
      cylinder model and phantom measurements with capillary plates to examine the
      relationship between the acquisition parameters in DTI and the size of restricted
      structures, particularly their diameter and length, which we will refer to as
      "compartment size." We confirmed that normalized signal intensities in DTI
      measurements depend on diffusion time, which, in turn, depends on the separation
      and duration of the MPG, and they decrease with increase in compartment size.
      Furthermore, our simulation and phantom results suggest that use of a longer
      diffusion time effectively emphasizes fractional anisotropy to clarify the
      direction of nerve fibers.

PMID- 21720115
TI  - Dynamic MR findings of ductal carcinoma in situ within a fibroadenoma.
AB  - We report magnetic resonance (MR) imaging findings of ductal carcinoma in situ
      (DCIS) within a fibroadenoma in a 42-year-old woman. Dynamic MR imaging revealed
      the mass to have 2 components with different kinetics. A nodular area within the
      mass showed faster initial enhancement followed by earlier washout and was
      histologically proven to be DCIS. Dynamic MR imaging reflected differences in
      vascularity between the fibroadenoma and DCIS, and parameter color maps generated
      from the dynamic data clearly demonstrated the extent of the DCIS.

PMID- 21720116
TI  - Spindle cell carcinoma of the breast: MR findings correlated with histopathology.
AB  - We correlate findings from magnetic resonance (MR) imaging and pathology in a 55
      year-old woman with spindle cell carcinoma of the breast. Pathological
      examination showed a fibrous capsule at the margins and abundant fibromyxoid
      stroma within the mass. Spindle cell carcinoma may be included in the
      differential diagnosis of expanding round masses with internal components that
      demonstrate rapid initial enhancement with high signal intensity on T(2)-weighted
      images in postmenopausal women.

PMID- 21720117
TI  - 13C MR imaging of methionine-rich gliomas at 4.7T: a pilot study.
AB  - We explored the feasibility of using carbon-13 ((13)C) magnetic resonance imaging
      ((13)C-MRI) to depict (13)C-labeled methionine-enriched gliomas at 4.7 tesla. We
      transplanted 2 types of glioma cells separately to 2 subcutaneous tissue sites on
      the backs of mice weighing 15 to 20 g. After confirming tumor growth, we used
      (13)C-MRI and (1)H-MRI to scan 4 mice that had been administered (13)C-labeled
      methionine and 2 control mice. (13)C-MRI of all 4 transplanted mice administered
      with (13)C-labeled methionine revealed 2 areas of hyperintensity that
      corresponded to the tumor sites on (1)H-MR images, but no such areas were
      visualized in transplanted controls. Our data suggest that (13)C-MRI can show the
      accumulation of (13)C-labeled tracer by gliomas.

PMID- 21720118
TI  - [Aflatoxin biosynthesis].

PMID- 21720119
TI  - Determination of carbendazim, thiophanate, thiophanate-methyl and benomyl
      residues in agricultural products by liquid chromatography-tandem mass
      spectrometry.
AB  - A simple and reliable liquid chromatographic-tandem mass spectrometric (LC-MS/MS)
      method was developed for carbendazim (MBC), thiophanate (TE), thiophanate-methyl
      (TM) and benomyl (BM) in agricultural products. These compounds were extracted
      from agricultural products with methanol after addition of sodium L-ascorbate. BM
      was hydrolyzed to MBC during the extraction with methanol. TE and TM were
      cyclized to ethyl 2-benzimidazole carbamate (EBC) and MBC by refluxing at 120 
      degrees C for 30 min with copper acetate in 50% acetic acid. MBC and EBC were
      cleaned up by an n-hexane wash and extraction with ethyl acetate and determined
      by LC-MS/MS. The mean recoveries from 10 agricultural products were in the range
      of 75.8-100.0%, and the relative standard deviations of 5 experiments were in the
      range of 1.5-9.2% at concentrations equal to the maximum residue limits (MRLs).
      The calibration curves were made by using commercial MBC and EBC as reference
      analytical standards without refluxing. The quantification limits were 0.01 mg/kg
      (as MBC), which is the uniform limit in the positive list system for agricultural
      chemical residues in foods in Japan.

PMID- 21720120
TI  - [Analytical method of clofencet in animal fishery products by LC/MS].
AB  - A method for the determination of clofencet in animal and fishery products was
      developed, using liquid chromatography with electrospray ionization mass
      spectrometry (LC/ESI-MS). The sample was homogenized with water and hexane, and
      the homogenate was extracted with acetonitrile, then acetonitrile-water (4 : 1).
      An aliquot of the crude extract was passed through a C18 cartridge column (1,000
      mg), and the eluate was concentrated. A solution of 10% sodium chloride and 1%
      sodium hydrogen carbonate, and ethyl acetate were added to the residue, and the
      mixture was shaken. After shaking, the aqueous phase was recovered and acidified
      with hydrochloric acid, and then clofencet was extracted with ethyl acetate. The
      extract was evaporated to dryness and the residue was dissolved in methanol-water
      (3 : 7). Clofencet was analyzed by LC/MS. The recoveries of clofencet from ten
      kinds of animal and fishery products were 77.8-97.8%, and the relative standard
      deviations were 0.6-5.8% (n=5). S/N of the peak of clofencet was >10 and no
      interfering peak was found in animal and fishery products fortified at 0.01
      mg/kg.

PMID- 21720121
TI  - [A sensitive analytical method for six aflatoxins in rainbow trout muscle and
      liver].
AB  - A highly sensitive analysis method for six aflatoxins (aflatoxin B1, B2, G1, G2,
      M1 and aflatoxicol) in rainbow trout muscle and liver was developed. Aflatoxins
      (AFs) were extracted with acetonitrile-water (9 : 1), purified on an
      immunoaffinity column, and subjected to HPLC with fluorescence detection after
      post-column photochemical derivatization. The recoveries of AFs at 0.05 MUg/kg
      spiking levels were 71.4-82.4% in muscle and 80.1-93.0% in liver, and the
      repeatability relative standard deviations (RSDr) were 0.87-4.6% in muscle and
      2.0-6.2% in liver. Limits of quantitation (LOQs) and limits of detection(LODs)of
      AFs were estimated to be 0.004-0.029 MUg/kg, and 0.002-0.012 MUg/kg,
      respectively.

PMID- 21720122
TI  - Analysis of trans-fat levels in total diet and one-serving samples using the
      verified GC-method and estimation of the intake in Japan.
AB  - In Japan, discussions on the regulation and labeling of trans-fat (TF) have under
      way for several years in the Food Safety Commission and the Consumer Affairs
      Agency. However, administrative measures for TF have not yet been taken, partly
      because of the insufficiency of scientific data in Japan. To provide data about
      the TF intake by Japanese, we determined the levels of TF contained in total diet
      samples and in food samples that were served as individual meals (one-serving
      samples). We analyzed 5 groups of total diet samples prepared in 11 regions
      throughout Japan, and 5 categories of one-serving samples using the GC-method
      after verifying its performance. The estimated daily intake of TF based on the
      analytical results of the total diet samples was around 500 mg and no significant
      difference was observed in the intake of the TF among the 11 surveyed regions. On
      the other hand, many one-serving samples classified into "hamburger", "pizza" and
      "Western food" categories contained more than 500 mg of TF per serving, the
      standard value in the labeling regulation in the United States. If these one
      serving meals are taken to represent one meal out of 3 in a day, the intake of TF
      can easily be expected to exceed the daily intake estimated through the analysis
      of the total diet samples.

PMID- 21720123
TI  - [Determination of nequinate and buquinolate in livestock products using liquid
      chromatography-tandem mass spectrometry].
AB  - We studied the simultaneous determination of nequinate and buquinolate, which are
      used as feed additives to prevent coccidiosis, by means of liquid chromatography
      coupled with tandem mass spectrometry (LC-MS/MS). The sample was extracted with
      acetonitrile, then loaded onto an HLB mini-column with 20% methanol. After clean
      up with 20% methanol, the analytes were eluted with acetonitrile-methanol (1 :
      1). The coccidiostats in the purified samples were determined using ESI-MRM mode
      LC-MS/MS with a sample matrix calibration curve. Mean recoveries of nequinate and
      buquinolate from 8 kinds of livestocks samples (chicken muscle, chicken liver,
      chicken heart, swine muscle, swine heart, cattle muscle, sheep muscle, egg) were
      in the range of 89.5% to 108.6%, and the relative standard deviation values were
      <20% (n=10) at the levels of 0.01 MUg/g and 0.05 MUg/g, respectively. The limits
      of quantification of these compounds were 0.001 MUg/g in each sample.

PMID- 21720124
TI  - [Single and 13-week oral toxicity study of fucoxanthin oil from microalgae in
      rats].
AB  - Single oral dose and 13-week oral subchronic toxicity studies of fucoxanthin
      containing oil extracted from microalga, Chaetoseros sp., were conducted in rats.
      In the single oral dose study, no mortality and no change related to the test
      material were observed. Thus, the 50% lethal dose of microalgal fucoxanthin oil
      is more than 2,000 mg/kg body weight. In the 13-week oral dose study, 0, 20 or
      200 mg/kg body weight of microalgal fucoxanthin oil was administered. The
      fucoxanthin-administered groups, showed no mortality and no abnormalities. This
      result suggested that the no-observed-adverse-effect level of fucoxanthin
      containing oil extracted from microalga Chaetoseros sp. was 200 mg/kg body weight
      under the tested subchronic dose condition.

PMID- 21720125
TI  - [Bacterial reverse mutation test and micronucleus test of fucoxanthin oil from
      microalgae].
AB  - Fucoxanthin-containing oil extracted from microalga, Chaetoseros sp., was
      subjected to genotoxicity studies, the bacterial reverse mutation test and the
      micronucleus test in mice. The number of revertant colonies in fucoxanthin oil
      treated plates of all strains tested was less than twice the number of colonies
      in the negative control, regardless of the presence of the metabolic activator in
      the bacterial reverse mutation test. In the micronucleus test, 500, 1,000, 2,000
      mg/kg body weight of fucoxanthin oil was administered orally to mice. There was
      no significant increase in micronucleus frequency in bone marrow cells. These
      results suggest that fucoxanthin oil does not exhibit genotoxicity.

PMID- 21720126
TI  - [Evaluation of the possibility that free fatty acids cause false-positive result
      in diarrhetic shellfish poisoning mouse bioassay in actual use].
AB  - Midgut glands of bivalves are used for the mouse bioassay of diarrhetic shellfish
      poison (DSP). A large quantity of free fatty acids (FFAs) causes a false positive
      outcome in the assay. To examine whether this is likely to occus under conditions
      of actual use, we analyzed the contents of the FFAs in the enlarged midgut glands
      during gametogenesis of Japanese scallops Patinopecten yessoensis that had been
      caught at two points in Hunka Bay on March 27, 2006, because the content of FFAs
      may increase with activation of lipogenesis for gametogenesis. Fatty acids (FAs)
      were measured with fluorometric high-performance liquid chromatography after
      derivatization with 9-anthryldiazomethane. The total FFAs (14 : 0, 16 : 0, 18 :
      0, 16 : 1, 18 : 1, 18 : 4, 20 : 5 and 22 : 6) represented 3.3-4.2 wt% of the
      lipid. The toxic FFAs accounted for 40-43 wt% of the total FFAs. Content of each
      FFA (18 : 1, 2.7-5.0 mg/g lipid; 18 : 4, tr.-2.0 mg/g; 20 : 4, n.d.; 20 : 5, 8.0
      9.1 mg/g and 22 : 6, 2.0-2.1 mg/g) was lower than the lethal dose tentatively
      calculated from the relative toxicity. It appears that the likelihood of FFAs
      causing false-positives in the mouse bioassay is low if the sample is fresh and
      is extracted immediately after homogenizing.

PMID- 21720127
TI  - [Determination of histamine in fish and fish products by tandem solid-phase
      extraction].
AB  - A simple and practical method was developed for the determination of histamine in
      fish and fish products by solid-phase extraction and fluorescence derivatization.
      Histamine was extracted with trichloroacetic acid. The extract was neutralized
      and diluted with phosphate buffer (pH 6.8), and cleaned up with a tandem
      connected octadecyl silica (ODS) and strong cation exchange silica (SCX)
      cartridge. After removal of the solvent, histamine was derivatized with
      fluorescamine and analyzed by ion-paired reversed-phase high-performance liquid
      chromatography with fluorescence detection. Recovery tests of histamine from six
      kinds of fish and fish products showed acceptable recovery (83-92%) with low
      relative standard deviation (less than 5%). This method could be useful for
      determination of histamine in fish.

PMID- 21720128
TI  - [Applicability of DNA barcode for identification of fish species].
AB  - DNA barcoding is a species identification technique, which uses a very short DNA
      sequence from a region of approximately 650 base-pairs in the 5'-end of the
      mitochondrial cytochrome c oxidase subunit I gene as a marker to identify species
      of mammals and fishes. The applicability of DNA barcoding for identification of
      fish species consumed in Japan was studied. Among thirty-one fresh or processed
      fishes were obtained from the market, two samples could not be identified due to
      lack of data in the Barcode of Life Data (BOLD) database. However, BLAST-search
      of 16S rRNA genes in the National Center for Biotechnology Information (NCBI)
      database and the PCR-RFLP method published by the Food and Agricultural Materials
      Inspection Center (FAMIC) were found to be applicable to identify these 2 fishes.
      The results show that the DNA barcoding technique is potentially useful as a tool
      for confirming the proper labeling of fish species in the Japanese market.

PMID- 21720129
TI  - [Basic concept for the inspection of imported foods].
AB  - According to Article 4 of the Food Safety Basic Law (Law No. 48 of 2003), food
      safety must be ensured by taking necessary measures appropriately at each step of
      the food supply process both in Japan and overseas. From this viewpoint, for
      ensuring safety of imported foods further, the quarantine stations have
      obligations such as confirmation of the import-notification documents submitted
      under Article 27 of the Law, issue of inspection orders in accordance with
      Article 26 of the Law for imported foods suspected with high probability of
      violating the Act (in order to prevent harm to public health from the perspective
      of food sanitation), and implement of monitoring inspection under Article 28 of
      the Law to enforce checking of the food-sanitation conditions of various imported
      foods. If a quarantine station or local organization (including prefectures,
      cities and specially designated wards that operate public health centers)
      identify any violation of the Law, the Ministry of Health, Labour and Welfare
      (hereinafter referred to as "the MHLW"), the quarantine station and the related
      prefecture shall cooperate to take appropriate measures to help the corresponded
      importer recall the food as soon as possible. In addition, taking measures to
      prevent recurrence of such violations by demonstration of examples of violations
      and guidance to importers. Under the recent situation of accidents such as
      addition of toxic substances to the food, it is important to make continuous
      efforts for achieving food safety in exporting countries. With recognition that
      assurance of the safety of the consumer from foodborn illness, it is necessary
      for the MHLW, the Agency of Consumer Affaires, local governments and related
      offices to make active efforts together through risk evaluation, risk management
      and the risk communication for 1 while measuring the communication.

PMID- 21720130
TI  - [Food safety viewed from the registration and inspection agencies].
AB  - When food safety is mentioned, people would think about food which is in
      compliance with Food Sanitation Act and standard, and edible food. Because there
      is difference in terms of food and additives standards between Japan and other
      countries, a variety of food cannot be imported from foreign countries to Japan.
      In addition, in 2006, with the introduction of the Positive List, which takes a
      close-up of pesticide remained in food and anti-biotic, we adopted an effective
      policy towards imported food which does not reach the national standards. On one
      hand, in order to ensure food safety, domestic producers, hotels, fast food
      stores, and restaurants all try to strengthen management on food quality and
      employees health. However, food poisoning happens frequently. Chemicals and
      natural poisoning play a part but the major part is played by micro-organism
      (bacteria). So it become more and more important to develop food safety policies
      to avoid harm from bad food. Therefore, as an authority with the responsibility
      of quarantine, inspection and registration, it is important to conduct food
      inspection and it is even more important to provide comprehensive suggestions.

PMID- 21720131
TI  - [Problems in LC-MS/MS analysis to ensure food safety].
AB  - An accurate analysis is required to address various issues concerning the food
      safety. Many risk factors, such as agricultural chemical residues, residual
      veterinary drugs, mycotoxins, food additives, and carcinogens produced during
      food processing may be present in foodstuffs. High-performance liquid
      chromatograph-tandem mass spectrometry (LC-MS/MS) is an analytical system
      advanced in terms of sensitivity, selectivity, and flexibility. The system has
      been widely applied to food analysis. Food contains a wide variety of nutritional
      components, which may cause interference with food analyses. Then, sample
      preparation to remove such interference and an appropriate choice of an
      analytical technique is required. Even with LC-MS/MS, the analytical reliability
      may be reduced by matrix effects, due to interference from food components. In
      this review, we summarize issues on using LC-MS/MS to achieve good analyses for
      the food safety and discuss how to address it. The topic especially focuses on
      matrix effects.

PMID- 21720132
TI  - [Safety of food additives in Japan].
AB  - Recently, many accidents relating to food happened in Japan. The consumer's
      distrust for food, food companies, and the administration is increasing. The
      consumer especially has an extreme refusal feeling for chemicals such as food
      additives and agricultural chemicals, and begins to request agricultural chemical
      free vegetables and food additive-free food. Food companies also state no
      agricultural chemicals and no food additives to correspond with consumers'
      request and aim at differentiating. The food additive is that the Ministry of
      Health, Labour and Welfare specifies the one that person's health might not be
      ruined by providing for Food Sanitation Law Article 10 in our country. The
      standard for food additives and standard for use of food additives are provided
      according to regulations of Food Sanitation Law Article 11. Therefore, it is
      thought that the food additive used is safe now. Then, it reports on the
      procedure and the safety examination, etc. in our country for designation for
      food additive this time.

PMID- 21720133
TI  - [Efficient construction of nitrogen-containing heterocycles utilizing CN
      functional groups and its application to the synthesis of natural products].
AB  - Viridicatin derivatives were synthesized from cyanoacetanilides utilizing the CN
      groups as electron-withdrawing groups and leaving groups. Also, the key scaffolds
      of glycocitlones were constructed via the intramolecular Houben-Hoesch-type
      reactions of cyanoacetanilides where the CN groups functioned as electrophiles.
      It was found that Houben-Hoesch-type reactions of cyanoacetanilides were promoted
      by alpha-functionalization such as perfluoroacylation and N,N
      dimethylaminomethylenation and that introduction of such substituents at alpha
      position with respect to the CN groups greatly influenced the physical properties
      and chemical reactivity of the CN groups.

PMID- 21720134
TI  - [Roles of ATP receptors in the regulation of various functions in spinal
      microglia].
AB  - It is shown that glial cells have a pivotal influence on the formation of
      neuronal network in central nerve system. Moreover, spinal microglia has some
      important roles in the development and progression of various neurological
      disorders. Therefore, it is possible that modulation of microglial activity may
      be sufficient to alleviate those harmful responses. ATP is one of signaling
      molecules in the spinal cord, and involved in regulation of several microglial
      functions through the binding of P2X and P2Y receptors. Thus, I focused on the
      ATP-mediated regulation mechanisms for the two important proteins, which are p38
      MAP kinase and excitatory amino acid transporters (EAATs), in cultured spinal
      microglia. Mounting evidence indicates that p38 in spinal microglia has crucial
      roles in some neurological diseases. Furthermore, it is recently suggested that
      microglial EAATs might participate in the homeostasis of glutamate in synapses.
      This review summarizes our finding regarding the involvement of P2Y receptors and
      beta-adrenergic receptors in the regulation of p38 phosphorylation, and the
      mechanism of P2X7 receptor-mediated downregulation of EAATs function.

PMID- 21720135
TI  - [Elucidation of carbohydrate functions in cell membranes--development of
      molecular tool containing carbohydrate ligand and elucidation of interface
      phenomena of glycolipid].
AB  - Glycosphingolids and glycoproteins in cell membrane are thought to play important
      roles in variety biological phenomena. Our interests focused on elucidation of
      their functions at the molecular level. We are especially interested in organic
      chemistry and physical chemistry of carbohydrates. Physical part-Surface of
      Langmuir-Blodgett (LB) films which comprised of various gangliosides,
      sphingolipids and cholesterol are observed by atomic force microscopy (AFM). We
      studied distribution of model compounds related to an antigenic epitope from
      Bupleurum falcatum L. in G(M3) (GM3)-DPPC monolayers. We also investigated
      relation between disease and glycolids in cell membrane. Chemical part-New
      molecular tools for the elucidation of carbohydrate roles using photoaffinity
      labeling were developed. We showed that the structural difference between closed
      ring- and open ring-type carbohydrates affected binding affinity to proteins.
      This study confirmed that carbohydrate structure, in both non-reducing end and
      reducing end sugars, is deeply related to the recognition event between
      carbohydrates and proteins. As a result, they will be used in future studies to
      elucidate carbohydrate functions on cell surfaces.

PMID- 21720136
TI  - [New treatment strategy for adult T-cell leukemia targeting for anti-tumor
      immunity and a longevity gene-encoded protein].
AB  - Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm
      with a poor prognosis, developing after long-term infection with human T-cell
      leukemia virus-1 (HTLV-1). Multiple factors (e.g., virus, host cells, epigenetic
      aberrations, and immune factors) have been implicated in the development of ATL,
      although the underlying mechanisms of leukemogenesis have not been fully
      elucidated. Despite recent progress in both chemotherapy and supportive care for
      hematological malignancies, the prognosis of ATL is still poor; overall survival
      at 3 years is only 24%. New strategies for the therapy and prophylaxis of ATL
      (e.g., vaccines and novel molecular target agents) are still required. This
      article reviews new strategy of ATL treatment targeted for HTLV-1-specific
      cytotoxic T-lymphocytes (CTLs) and SIRT1, a longevity gene-encoded protein. HTLV
      1-specific CTLs play a critical role in the host immune response against HTLV-1.
      We have described here the decreased frequency and function of HTLV-1-specific
      CD8+ T cells in ATL patients and the efficient induction of the HTLV-1-specific
      CTLs response in human leukocyte antigen-A* 0201-transgenic mice by the HTLV
      1/hepatitis B core chimeric particle and oligomannose-coated liposomes
      encapsulating HTLV-1 epitope without adjuvant, suggesting that the efficient
      antigen delivery system and CTL induction can be exploited to develop a
      prophylactic vaccine model against tumors and infectious diseases. Furthermore,
      our studies suggest that SIRT1, a longevity gene-encoded protein, is a crucial
      anti-apoptotic molecule in ATL cells, and that SIRT1 inhibitors may be useful
      therapeutic agents for leukemia, especially in patients with ATL. These studies
      targeted for anti-tumor immunity such as vaccine and SIRT1 may support the new
      prophylactic and therapeutic approach for ATL.

PMID- 21720137
TI  - [Investigation of the combination of aspirin with non-steroidal anti-inflammatory
      drugs].
AB  - It has been reported that non-steroidal anti-inflammatory drugs (NSAIDs) interact
      with aspirin to influence its antiplatelet effect. For example, there have been
      reported that the rate of platelet aggregation inhibition associated with aspirin
      was significantly decreased when ibuprofen was taken before administration of
      aspirin, as compared with aspirin alone. In this study, we investigated the
      prescriptions on combination of aspirin with NSAIDs. The subjects were consisted
      of 1212 patients who were prescribed aspirin in March, 2008 in Tokai University
      Hachioji Hospital. The patients prescribed combination of aspirin with NSAIDs
      were 8.1% and 18.6% of those were prescribed in the order of adminstration to
      induce drug interaction. The pharmacists should provide information about drug
      interactions of aspirin with NSAIDs to the doctors and patients, and it is
      necessary to pay attention of these interactions.

PMID- 21720138
TI  - Synthesis, anti-inflammatory and analgesic evaluation of thioxoquinazolinone
      derivatives.
AB  - A series of 3-substituted-2-thioxoquinazolin-4(3H)-one derivatives have been
      synthesized and their structures have been elucidated on the basis of IR, (1)H
      NMR, elemental analysis and mass spectroscopic studies. Anti-inflammatory and
      analgesic activity of the synthesized compounds was evaluated by Carrageenan
      induced rat paw edema method and Eddy's hot plate method respectively. Among the
      synthesized compounds N-(4-hydroxyphenyl)-N-(4-oxo-3-phenyl-2-thioxo-3,4
      dihydroquinazolin-1(2H)methyl)acetamide (PTQ01) showed excellent anti
      inflammatory activity. N-(4-ethoxyphenyl)-N-(3-(naphthalen-2yl)-4-oxo-2-thioxo
      3,4-dihydroquinazolin-1(2H)-yl)methyl)acetamide (NTQ02), N-(4-Hydroxyphenyl)-N
      ((3-naphthalen-2-yl)-4-oxo-2-thioxo-3,4-dihydorquinazolin-1(2H)
      ylmethyl)acetamide (NTQ01), N-((3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4
      dihydoquinazolin-1(2H)-yl)methyl)-N-(4-hydroxyphenyl)acetamide (ETQ01) N-(3-(4
      ethoxyphenyl)-4-oxo-2thioxo-3,4-dihydroquinazolin-1(2H)-ylmethyl)-N-(4
      hydroxyphenyl)acetamide (ETQ04), N-(4-ethoxyphenyl)-N-((4-oxo-3-phenyl-2-thioxo
      3,4-dihydoquinazolin-1(2H)-yl)methyl)acetamide (PTQ02) and N-(4-ethoxyphenyl)-N
      (3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydoquinazolin-1(2H)-yl)methyl)acetamide
      (ETQ02) at a dose of 20 mg/kg exhibited significant anti-inflammatory activity
      compared to that of standard drug diclofenac sodium. The compound 2-(2,3
      dimethylphenyl)(3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydroquinazolin-1-2H)
      1ylmethylamino)benzoic acid PTQ03 and sodium 2-(2-((2,6-dichlrophenyl)(3-(4-oxo-2
      thioxo-3,4-dihydroquinazolin-1(2H)-yl)methyl)amino)phenylacetate (PTQ04) showed
      moderate anti-inflammatory activity. The compounds PTQ01, PTQ02, PTQ04, ETQ01 and
      ETQ02 showed significant analgesic activity compared with that of standard drug
      pentazocin.

PMID- 21720139
TI  - [Evaluation of the development of gastroduodenal lesions in patients treated with
      low-dose aspirin or non-steroidal anti-inflammatory drugs].
AB  - Aspirin irreversibly inhibits the enzyme cyclooxygenase-1 and depresses the
      production of thromboxane A(2), and also exerts antiplatelet effects. On the
      other hand, it also depresses the production of prostaglandin E(2) (PGE(2)) and
      induces gastroduodenal lesions, which are often seen in patients taking aspirin.
      The aim of this study was to clarify the degree of gastroduodenal lesions induced
      by low-dose aspirin. We investigated the incidence rate of such lesions induced
      by aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), and performed
      theoretical evaluations in a retrospective study. The incidence rates of
      gastroduodenal lesions in the low-dose aspirin (n=1103) and NSAIDs (n=1856)
      groups were 2.54% and 0.27%, respectively, which was significantly greater in the
      aspirin group. Furthermore, the calculated value of inhibition rate of gastric
      PGE(2) was significantly correlated with the actual value after administration of
      aspirin or NSAIDs (r=0.902, p<0.05), which suggested that the calculated value
      reflected the actual value. The calculated value of aspirin (98.9%) was higher
      than that of NSAIDs (3.67-70.8%) after administration of the drugs with the
      standard doses. Our findings indicate that the incidence rate of gastroduodenal
      lesions induced by low-dose aspirin was higher than that of those induced by
      NSAIDs. Therefore, we were able to perform a theoretical evaluation of the
      occurrence of gastroduodenal lesions.

PMID- 21720140
TI  - [Improved spectrophotometric determination of total iron and iron(III) with o
      hydroxyhydroquinonephthalein and their characterization].
AB  - Simultaneous and fractional determination of iron(II) and iron(III) was
      accomplished with o-hydroxyhydroquinonephthalein (QP) in the presence of poly (N
      vinyl pyrrolidone). In the determination of total iron (iron(II)+iron(III)),
      Beer's law was obeyed in the range of 0.02-0.67 MUg.ml(-1), with an effective
      molar absorptivity (at 570 nm) and a relative standard deviation of
      1.30*10(5).l.mol(-1).cm(-1) and 0.77% (n = 8), respectively. This method was
      about 10-15 times and more than the methods using 1,10-phenanthroline and 2,2'
      bipyridine. In addition, the iron-QP complex was characterized using
      spectrophotometry and the electron spin resonance. This method was successfully
      applied to assays of total iron and iron(III) in pharmaceutical preparations.

PMID- 21720141
TI  - Anti-gastric actions of eugenol and cinnamic acid isolated from Cinnamomi
      Ramulus.
AB  - We investigated the evidence of gastric protection for ulcer and gastritis by
      Cinnamomi Ramulus (Cinnamomum cassia Blume, Geiji, CR) extract and its several
      constituents. CR ethanolic extract showed the potent antioxidant activity and
      cytotoxicity of Helicobacter pylori (H. pylori) and acid-neutralizing capacity.
      Especially, eugenol exerted a significant antioxidant activity and inhibited the
      colonization of H. pylori. In vivo test, eugenol and cinnamic acid significantly
      inhibited HCl/ethanol-induced gastric lesions and increased the mucus content
      though they didn't inhibit gastric secretion effectively. Taken together, eugenol
      and cinnamic acid, which were isolated from CR, exhibited the antioxidant
      activity in vitro and protective effect against gastric damage in vivo through
      stimulation of mucus secretion and so on. It suggested that they are useful as
      the neutraceuticals for gastritis.

PMID- 21720142
TI  - Inhibition of D-amino acid oxidase activity by antipsychotic drugs evaluated by a
      fluorometric assay using D-kynurenine as substrate.
AB  - A facile fluorometric assay using D-kynurenine as a substrate was utilized for
      evaluating the inhibition of D-amino acid oxidase (DAAO), which is one of the
      products of a susceptibility gene for schizophrenia, by commercial antipsychotic
      drugs, namely, chlorpromazine (CPZ), carbamazepine, sulpiride, quetiapine, and
      imipramine. CPZ inhibited DAAO (65.8 +/- 13.2 MUM, n = 3) as reported previously,
      and other drugs also inhibited DAAO activity. Among these, quetiapine had the
      smallest IC(50) value (19.5 +/- 2.60 MUM, n = 3). The proposed assay can be
      useful for the evaluation or screening of DAAO-inhibitory drugs.

PMID- 21720143
TI  - [Surveillance study on the needs for self-medication of local residents and
      community pharmacists in Fukuyama].
AB  - In recent years, self-medication is promoted to control the health care cost of
      aged people in Japan. On the other hand, there are many pharmacists who are
      perplexed in diversification of work with promotion of self-medication because of
      shortage of information, including the knowledge of an over-the-counter drug,
      health food, etc. It is therefore needed to design an efficient education program
      for pharmacists, especially in aging society such as Fukuyama. In this study, we
      investigated the needs for self-medication of local residents and community
      pharmacists in order to clarify the high-priority education themes for promotion
      of self-medication in Fukuyama. The pharmacist's needs were extracted by the KJ
      method and prioritized by the two-dimensional developed leaf method, and the
      local resident's needs were extracted by questionnaire survey from 420 general
      populations who live in Fukuyama. As a result, we found that the community
      pharmacists were especially in need of acquisition of the knowledge about "health
      food" and "food", and the local residents were especially in need of consultation
      with community pharmacists about "medicine", "side effect of medicine", "health
      food" and "food". Moreover, we also found that sixty percent of local residents
      did not have knowledge about interaction of "medicine" and "health food" while
      the half of them was taking in "health food". From the above result, knowledge
      improvement of "health food", "food" and "interaction of medicine and health
      food" in addition to "medicine" and "side effect of medicine" is the high
      priority education themes for local residents and community pharmacists to
      promote self-medication in Fukuyama.

PMID- 21720144
TI  - [Actual state of understanding and utilization of "home pharmacy" in residents
      and their regional differences].
AB  - To know the actual states of understanding and utilization of "home pharmacy" in
      regional residents and their regional differences, we performed questionnaire
      survey for the residents in Ueda-shi in Nagano and the Kita-tama area in Tokyo,
      where it was found in the past survey that the medical activities as "home
      pharmacy" in Ueda-shi was remarkably higher than those in the Kita-tama area. By
      the present survey it was confirmed that the percentages of the person who keeps
      "home pharmacy" and of the person who fixes a pharmacy to get a filled
      prescription were remarkably higher in the residents of Ueda-shi than those of
      the Kita-tama area. The level of understanding of "home pharmacy" was also higher
      in the residents of Ueda-shi. These results suggested that the spread of "home
      pharmacy" is influenced by the extent of activity of regional pharmacy and the
      regional society of pharmacists.

PMID- 21720145
TI  - [Migration of eight harmful elements from household products made with synthetic
      resin that infants may swallow by mistake].
AB  - Harmful elements are used as stabilizers and colorants in synthetic resin
      products. Accidental ingestion of harmful elements from such synthetic resins by
      infants is a dangerous health hazard. The Japanese Food Sanitation Law and the
      International Standard ISO 8124-3 "Safety of toys-Part 3: Migration of certain
      elements" control the levels of migrated harmful elements, such as lead or
      cadmium, from infants toys. However, the levels of migrated harmful elements from
      household products that are not infants toys are not controlled, since they are
      not covered by the law or standard. Therefore, we investigated the level of eight
      harmful elements (antimony, arsenic, barium, cadmium, chromium, lead, mercury and
      selenium) migrated from household products made of synthetic resin that infants
      may swallow by mistake. The extraction test of ISO 8124-3: 2010 was executed in
      135 products (total 150 specimens), and the concentration of these elements was
      measured by inductively coupled plasma mass spectroscopy (ICP-MS). As a result,
      1810 mg/kg and 1660 mg/kg of lead, exceeding the maximum acceptable level of the
      ISO standard, migrated from two products. In addition, lead and/or chromium at
      levels more than 1/10 of the maximum acceptable levels of the ISO standard
      migrated from four products. Household products that infants may swallow by
      mistake should ideally not release harmful elements such as lead and chromium.

PMID- 21720146
TI  - [Isomeric analysis of synthetic cannabinoids detected as designer drugs].
AB  - Recently, many psychotropic herbal products, named such as "Spice", were
      distributed worldwide via the Internet. In our previous study, several synthetic
      cannabinoids were identified as adulterants in herbal products being available in
      Japan due to their expected narcotic effects. Among those, two derivatives of
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC), which is major psychotropic
      cannabinoid of marijuana, cannabicyclohexanol (CCH, 3-[2-hydroxy-4-(2-methylnonan
      2-yl)phenyl]cyclohexan-1-ol) and CP-47,497 (3-[2-hydroxy-4-(2-methyloctan-2
      yl)phenyl]cyclohexan-1-ol), have been controlled as designated substances (Shitei
      Yakubutsu) under the Pharmaceutical Affairs Law since November 2009. CCH was
      detected together with its trans-form (1-epimer) in many herbal products, and CCH
      and CP-47,497 have two chiral centers in the structures. However, the
      pharmaceutical activities of the isomers of CCH have not been reported. This
      study presents chiral separations of CCH, its trans-form and CP-47,497 in the
      products using LC-circular dichroism (CD) and LC-MS analyses. The enantiomeric
      pairs of CCH, its trans-form and CP-47,497 were separated, respectively.
      Subsequently, the analyses of the herbal products showed that CCH and its trans
      form existed as mixtures of enantiomers and the relative ratios of CCH and the
      trans-form enantiomers ranged from 42/58% to 53/47% and from 33/67% to 52/48%,
      respectively.

PMID- 21720147
TI  - Comparison of nephrostomy drainage types following percutaneous nephrolithotomy
      requiring multiple tracts: single tube versus multiple tubes versus tubeless.
AB  - OBJECTIVES: Placement of multiple nephrostomy tubes is the standard practice
      after completion of multitract percutaneous nephrolithotomy (PCNL) to reduce
      hemorrhage and urinary extravasation.We compared the outcomes among tubeless,
      single nephrostomy drainage and multiple nephrostomy drainage tubes following
      PCNL requiring multiple tracts. METHODS: We retrospectively analyzed the data of
      115 patients who underwent PCNL using multiple (two or more) access tracts.
      Patients were categorized into three groups: one nephrostomy tube for each tract
      (group 1, n = 43); single nephrostomy tube placement (group 2, n = 51), and no
      nephrostomy drainage with antegrade placement of a double-J stent (group 3, n =
      21). RESULTS: The three groups had comparable demographic data. The differences
      in operative times, average hemoglobin decrease and complication rates for the
      three groups were not statistically significant. The average hospital stay in the
      tubeless group (mean 2.1 days) was significantly shorter than that in group 1
      (4.2 days) and group 2 (3.5 days). The postoperative analgesic requirement was
      significantly higher in group 1 compared to group 2 (p < 0.05) and group 3 (p <
      0.001). Stones were completely cleared in 83.7, 84.3 and 85.7% of patients, which
      increased to 90.7, 92.1, and 95.2% with adjunctive therapies in groups 1, 2 and
      3, respectively. CONCLUSIONS: Single or no nephrostomy drainage following
      multitract PCNL offers the potential advantages of decreased postoperative
      analgesic requirement, and hospital stay without increasing the complications.

PMID- 21720148
TI  - The general public's understanding and perception of direct-to-consumer genetic
      test results.
AB  - BACKGROUND/AIMS: Direct-to-consumer (DTC) genetic testing allows consumers to
      discover their risk for common complex disorders. The extent to which consumers
      understand typical results provided by DTC genetic testing is currently unknown.
      Misunderstanding of the results could lead to negative consequences including
      unnecessary concern, false reassurance or unwarranted changes in screening
      behaviors. We conducted a study to investigate consumers' perceptions and
      understanding of DTC test results. METHODS: An online survey was posted on
      Facebook that included questions relating to 4 sample test results for risk of
      developing colorectal cancer, heart disease and skin cancer. Genetic counselors
      were used as a comparison group. RESULTS: 145 individuals from the general public
      and 171 genetic counselors completed the survey. A significant difference was
      found between the way the general public and genetic counselors interpreted the
      meaning of the DTC results. The general public respondents also believed that
      results in all 4 scenarios would be significantly more helpful than the genetic
      counselors did. Although the majority of general public respondents rated the
      results as easy to understand, they often misinterpreted them. CONCLUSIONS: These
      findings imply that the general public has the potential to misinterpret DTC
      results without appropriate assistance. Further research is needed to explore
      optimal methods of providing DTC test results and ways to minimize the risk of
      negative consequences for consumers.

PMID- 21720149
TI  - Adult height in girls with delayed pubertal growth.
AB  - BACKGROUND/AIMS: Boys with constitutional delay of growth and puberty (CDGP) with
      early reduction in relative height before the onset of puberty will have adult
      height (AH) clearly below their target height (TH). Characteristics of growth in
      girls with CDGP are poorly known. We examined whether girls with CDGP attain
      their TH and whether early reduction in height SDS influences their AH. We also
      investigated effects of low-dose estrogen on AH. METHODS: We investigated growth
      of 39 women (7 treated with low-dose estrogen) with CDGP history. We compared AH
      between estrogen-treated and untreated subjects, and used multiple linear
      regression to investigate the influence of various growth characteristics, e.g.
      height SDS changes between different ages in childhood, on AH. RESULTS: AH was
      similar in estrogen-treated and untreated subjects. Reduction of height SDS
      between 3 and 8 years was significantly associated with the difference between AH
      and TH (regression coefficient 0.8, 95% confidence interval 0.1-1.5). Overall,
      49% of subjects had AH >0.50 SDS below TH. CONCLUSION: A proportion of CDGP girls
      do not attain AH consistent with their TH. Reduction in height SDS in childhood
      predicts smaller AH. Low-dose estrogen treatment does not seem to influence AH in
      girls with CDGP.

PMID- 21720150
TI  - Mosaicism in segmental Darier disease: an in-depth molecular analysis quantifying
      proportions of mutated alleles in various tissues.
AB  - Darier disease is an autosomal dominant genodermatosis caused by germline
      mutations in the ATP2A2 gene. Clinical expression is variable, including rare
      segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic
      counseling of segmental Darier patients is complex, as risk of transmitting a
      nonsegmental phenotype to offspring is of unknown magnitude. We present the first
      in-depth molecular analysis of a mosaic patient with segmental disease,
      quantifying proportions of mutated and normal alleles in various tissues.
      Pyrosequence analysis of DNA from semen, affected and normal skin, peripheral
      leukocytes and hair revealed an uneven distribution of the mutated allele, from
      14% in semen to 37% in affected skin. We suggest a model for segmental
      manifestation expression where a threshold number of mutated cells is needed for
      manifestation development. We further recommend molecular analysis of the ATP2A2
      gene in semen of male patients with segmental Darier disease to improve genetic
      counseling.

PMID- 21720151
TI  - Dimorphic expression of various transcription factor and steroidogenic enzyme
      genes during gonadal ontogeny in the air-breathing catfish, Clarias gariepinus.
AB  - In the present study the expression of 13 genes known to be involved in sex
      differentiation and steroidogenesis in catfish was analyzed during gonadal
      ontogeny by quantitative real-time RT-PCR. Dmrt1 and sox9a showed exclusive
      expression in male gonads while ovarian aromatase (cyp19a1) and foxl2 were
      abundant in differentiating female gonads. Most of the genes related to
      steroidogenesis were expressed only after gonadal differentiation. However, genes
      coding for 3beta-hydroxysteroid dehydrogenase (3beta-hsd), 17alpha
      hydroxylase/C17-20 lyase type 1 (cyp17) and steroidogenic acute regulatory
      protein (star) were barely detectable during gonadal differentiation. Ovarian
      aromatase, cyp19a1, which is responsible for estradiol-17beta biosynthesis in
      females, was expressed very early in the undifferentiated gonads of catfish,
      around 30-40 days post hatch (dph). The steroidogenic enzyme, 11beta-hydroxylase
      (cyp11b1) required for the production of 11-ketotestosterone (11-KT) was
      expressed only after differentiation of testis. These results suggest that
      estradiol-17beta has a critical role in ovarian differentiation, while the role
      of 11-KT in testicular differentiation is doubtful. In conclusion, dimorphic
      expression of dmrt1 and sox9a in gonads during early development is required for
      testicular differentiation, and sex-specific expression of cyp19a1 and foxl2 in
      females plays a critical role in ovarian development. Our study reveals that the
      critical period of gonadal differentiation in catfish starts around 30-40 dph
      when sex-specific genes showed differential expression.

PMID- 21720152
TI  - Ethical issues in recruiting prenatally diagnosed adults for research:
      Klinefelter syndrome as an example.

PMID- 21720153
TI  - Intravitreal ranibizumab for choroidal neovascularization secondary to
      pathological myopia: 12-month follow-up.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal ranibizumab in the
      treatment of choroidal neovascularization (CNV) due to pathological myopia (PM).
      METHODS: This retrospective case series studied outcomes in patients with CNV
      secondary to PM who were treated with intravitreal ranibizumab. Patients
      underwent complete ophthalmic evaluation, which included best-corrected visual
      acuity testing measured with Early Treatment Diabetic Retinopathy Study charts,
      optical coherence tomography (OCT) and baseline fluorescein angiography (FA).
      Indications for retreatment included the persistence of subretinal fluid on OCT
      as well as hemorrhages and new CNV on FA. Patients were followed for a minimum of
      12 months. RESULTS: We treated 29 eyes in 29 patients; the mean age was 56.8
      years. Thirteen eyes were naive, while 16 had been previously treated with
      photodynamic therapy or intravitreal bevacizumab. The mean initial visual acuity
      was 44.8 letters; at the 12-month follow-up, it was 53.7 letters. The mean OCT
      foveal thickness decreased by 35.3 MUm. Patients received an average of 1.38
      injections. Statistically significant differences were observed both in visual
      acuity and in central foveal thickness. All subgroups had favorable outcomes.
      None of the patients developed injection-induced complications or drug-related
      side effects. CONCLUSION: Intravitreal injection of ranibizumab appears to be
      safe and efficacious in patients with CNV secondary to PM followed over a 12
      month period.

PMID- 21720154
TI  - Genome-wide analysis of Sox genes in Medaka (Oryzias latipes) and their
      expression pattern in embryonic development.
AB  - Genes of the Sox family encode evolutionarily conserved high-mobility group box
      containing transcription factors, which play key roles in various events of
      developmental contexts. In this study, we identified 15 sox genes by searching
      for the high-mobility group domain in the medaka genome and by polymerase chain
      reaction using primers designed from the results obtained from homology protein
      alignment. All medaka sox genes except a novel sox gene, Olsox32, are encoded in
      5 groups as follows: 4 sox genes in group B; 3 sox genes in group D and F,
      respectively; 2 sox genes in group C and E, respectively, while no sox genes were
      found in groups A, G, H, I, and J. The medaka Olsox32 does not fall within any of
      the previously defined groups A-J. Here we have assigned it to a new group K.
      Together with the Sox protein sequences of other species, the phylogenetic
      relationship was analyzed and compared. Our findings point to recent sox gene
      loss, duplication and divergence occurring during the evolution of tetrapod and
      teleost lineages. The expression pattern shows that sox genes play a variety of
      roles in the early embryonic development of medaka.

PMID- 21720155
TI  - Chromosomal distribution of repetitive DNA sequences highlights the independent
      differentiation of multiple sex chromosomes in two closely related fish species.
AB  - The arrangement of 6 repetitive DNA sequences in the mitotic and meiotic sex
      chromosomes of 2 Erythrinidae fish, namely Hoplias malabaricus and Erythrinus
      erythrinus, both with a multiple X(1)X(1)X(2)X(2)/X(1)X(2)Y sex chromosome
      system, was analyzed using fluorescence in situ hybridization. The distribution
      patterns of the repetitive sequences were distinct for each species. While some
      DNA repeats were species-specific, others were present in the sex chromosomes of
      both species at different locations. These data, together with the different
      morphological types of sex chromosomes and the distinct chromosomal
      rearrangements associated with the formation of the neo-Y chromosomes, support
      the plasticity of sex chromosome differentiation in the Erythrinidae family. Our
      present data highlight that the sex chromosomes in fish species may follow
      diverse differentiation patterns, even in the same type of sex chromosome system
      present in cofamiliar species.

PMID- 21720156
TI  - Angiotensin II activation of mTOR results in tubulointerstitial fibrosis through
      loss of N-cadherin.
AB  - BACKGROUND/AIMS: Angiotensin (Ang) II contributes to tubulointerstitial fibrosis.
      Recent data highlight mammalian target of rapamycin (mTOR)/S6 kinase 1 (S6K1)
      signaling in tubulointerstitial fibrosis; however, the mechanisms remain unclear.
      Thereby, we investigated the role of Ang II on mTOR/S6K1-dependent proximal
      tubule (PT) injury, remodeling, and fibrosis. METHODS: We utilized young
      transgenic Ren2 rats (R2-T) and Sprague-Dawley rats (SD-T) treated with the Ang
      type 1 receptor (AT(1)R) blocker telmisartan (2 mg . kg(-1) . day(-1)) or vehicle
      (R2-C; SD-C) for 3 weeks to examine PT structure and function. RESULTS: Ren2 rats
      displayed increased systolic blood pressure, proteinuria and increased PT oxidant
      stress and remodeling. There were parallel increases in kidney injury molecule-1
      and reductions in neprilysin and megalin with associated ultrastructural findings
      of decreased clathrin-coated pits, endosomes, and vacuoles. Ren2 rats displayed
      increased Serine(2448) phosphorylation of mTOR and downstream S6K1, in concert
      with ultrastructural basement membrane thickening, tubulointerstitial fibrosis
      and loss of the adhesion molecule N-cadherin. Telmisartan treatment attenuated
      proteinuria as well as the biochemical and tubulointerstitial structural
      abnormalities seen in the Ren2 rats. CONCLUSIONS: Our observations suggest that
      Ang II activation of the AT(1)R contributes to PT brush border injury and
      remodeling, in part, due to enhanced mTOR/S6K1 signaling which promotes
      tubulointerstitial fibrosis through loss of N-cadherin.

PMID- 21720157
TI  - Clinical characteristics and cardiovascular outcomes of hemodialysis patients
      with atrial fibrillation: a prospective follow-up study.
AB  - BACKGROUND/AIMS: Among the cardiovascular complications in dialysis patients,
      atrial fibrillation (AF) is the most common arrhythmia. The purpose of this study
      was to clarify the characteristics and mortality of hemodialysis patients with
      AF, which are not completely elucidated. METHODS: The prevalence of AF in
      patients undergoing hemodialysis in our institutions was assessed. Patients with
      AF (AF group) and without AF (control group) were included in this study.
      Patients in the control group were matched for several important clinical risk
      factors. For further analysis, AF patients were divided into two groups on the
      basis of the type of AF (chronic AF (CAF) and paroxysmal AF (PAF) groups). These
      patients were evaluated for their clinical characteristics, laboratory data and
      echocardiographic parameters and prospectively followed up for 48 months.
      RESULTS: Among 328 study patients, 30 had AF (9.1%). Left atrial diameter (LAD)
      and the left ventricular mass index were significantly greater in the AF group
      than in the control group. Furthermore, cardiovascular and all-cause mortality
      and cumulative incidence of cardiovascular events were significantly higher in
      the AF group than in the control group, and tended to be higher in the CAF group.
      CONCLUSIONS: Our findings demonstrated that the prevalence of AF as 9.1% in
      hemodialysis patients, and that AF, especially CAF, were associated with high
      mortality.

PMID- 21720158
TI  - Adiponectin: sometimes good, sometimes bad?

PMID- 21720159
TI  - Effects of zinc and fluoride on the remineralisation of artificial carious
      lesions under simulated plaque fluid conditions.
AB  - The aim was to study the effects of zinc (Zn) and fluoride (F) on
      remineralisation at plaque fluid concentrations. Artificial carious lesions were
      created in 2 acid-gel demineralising systems (initially infinitely undersaturated
      and partially saturated with respect to enamel) giving lesions with different
      mineral distribution characteristics (high and low R values, respectively) but
      similar integrated mineral loss values. Lesions of both types were assigned to 1
      of 4 groups and remineralised for 5 days at 37 degrees C. Zn and F were added,
      based on plaque fluid concentrations 1 h after application, to give 4 treatments:
      231 MUmol/l Zn, 10.5 MUmol/l F, Zn/F combined and an unmodified control solution
      (non-F/non-Zn). Subsequently remineralisation was measured using
      microradiography. High-R lesions were analysed for calcium, phosphorus, F and Zn
      using electron probe micro-analysis. All lesions underwent statistically
      significant remineralisation. For low-R lesions, remineralisation was in the
      order F(a) < non-F/non-Zn(a) < Zn(a, b) < Zn/F(b), and for high-R lesions F(a) <
      non-F/non-Zn(b) < Zn(b) < Zn/F(c) (treatments with the same superscript letter
      not significantly different, at p < 0.05). Qualitatively, remineralisation
      occurred throughout non-F/non-Zn and Zn groups, predominantly at the surface zone
      (F) and within the lesion body (Zn/F). Electron probe micro-analysis revealed Zn
      in relatively large amounts in the outer regions (Zn, Zn/F). F was abundant not
      only at the surface (F), but also in the lesion body (Zn/F). Calcium:phosphate
      ratios were similar to hydroxyapatite (all). To conclude, under static
      remineralising conditions simulating plaque fluid, Zn/F treatment gave
      significantly greater remineralisation than did F treatment, possibly because Zn
      in the Zn/F group maintained greater surface zone porosity compared with F,
      facilitating greater lesion body remineralisation.

PMID- 21720160
TI  - Gastro-oesophageal reflux disease symptoms and tooth wear in patients with
      Sjogren's syndrome.
AB  - The aim of this study was to assess the prevalence of gastro-oesophageal reflux
      disease (GORD) symptoms and tooth wear in patients with Sjogren's syndrome (SS)
      compared with matched controls. GORD symptoms were assessed for 33 SS patients
      and 20 age- and sex-matched controls. Tooth wear was assessed in all patients and
      controls. The results were further analysed in two subgroups of SS patients and
      controls with and without GORD symptoms (SS patients without GORD symptoms: n =
      11, controls without GORD symptoms: n = 18). A higher proportion of SS patients
      reported suffering from heartburn and regurgitation than controls (p < 0.001 and
      p = 0.02, respectively). SS patients without GORD symptoms had a statistically
      significantly higher percentage of surfaces with tooth wear affecting dentine
      than controls (p < 0.001).

PMID- 21720161
TI  - Antimicrobial traits of tea- and cranberry-derived polyphenols against
      Streptococcus mutans.
AB  - There are over 750 species of bacteria that inhabit the human oral cavity, but
      only a small fraction of those are attributed to causing plaque-related diseases
      such as caries. Streptococcus mutans is accepted as the main cariogenic agent and
      there is substantial knowledge regarding the specific virulence factors that
      render the organism a pathogen. There has been rising interest in alternative,
      target-specific treatment options as opposed to nonspecific mechanical plaque
      removal or application of broad-spectrum antibacterials that are currently in
      use. The impact of diet on oral health is undeniable, and this is directly
      observable in populations that consume high quantities of polyphenol-rich foods
      or beverages. Such populations have low caries incidence and better overall oral
      health. Camellia sinensis, the plant from which various forms of tea are derived,
      and Vaccinium macrocarpon (American cranberry fruit) have received notable
      attention both for their prevalence in the human diet as well as for their unique
      composition of polyphenols. The biologically active constituents of these plants
      have demonstrated potent enzyme-inhibitory properties without being bactericidal,
      a key quality that is important in developing therapies that will not cause
      microorganisms to develop resistance. The aim of this review is to consider
      studies that have investigated the feasibility of tea, cranberry, and other
      select plant derivatives as a potential basis for alternative therapeutic agents
      against Streptococcus mutans and to evaluate their current and future clinical
      relevance.

PMID- 21720162
TI  - Early post-stroke cognition in stroke rehabilitation patients predicts functional
      outcome at 13 months.
AB  - OBJECTIVE: To identify prognostic factors associated with functional outcome at
      13 months in a sample of stroke rehabilitation patients. Specifically, we
      hypothesized that cognitive functioning early after stroke would predict long
      term functional outcome independently of other factors. METHODS: 163 stroke
      rehabilitation patients underwent a structured neuropsychological examination 2-3
      weeks after hospital admittance, and their functional status was subsequently
      evaluated 13 months later with the modified Rankin Scale (mRS) as outcome
      measure. Three predictive models were built using linear regression analyses: a
      biological model (sociodemographics, apolipoprotein E genotype, prestroke
      vascular factors, lesion characteristics and neurological stroke-related
      impairment); a functional model (pre- and early post-stroke cognitive
      functioning, personal and instrumental activities of daily living, ADL, and
      depressive symptoms), and a combined model (including significant variables, with
      p value <0.05, from the biological and functional models). RESULTS: A combined
      model of 4 variables best predicted long-term functional outcome with explained
      variance of 49%: neurological impairment (National Institute of Health Stroke
      Scale; beta = 0.402, p < 0.001), age (beta = 0.233, p = 0.001), post-stroke
      cognitive functioning (Repeatable Battery of Neuropsychological Status, RBANS;
      beta = -0.248, p = 0.001) and prestroke personal ADL (Barthel Index; beta = 
      0.217, p = 0.002). Further linear regression analyses of which RBANS indexes and
      subtests best predicted long-term functional outcome showed that Coding (beta = 
      0.484, p < 0.001) and Figure Copy (beta = -0.233, p = 0.002) raw scores at
      baseline explained 42% of the variance in mRS scores at follow-up. CONCLUSIONS:
      Early post-stroke cognitive functioning as measured by the RBANS is a significant
      and independent predictor of long-term functional post-stroke outcome.

PMID- 21720163
TI  - Quality of dementia diagnostic evaluation for ethnic minority patients: a
      nationwide study.
AB  - BACKGROUND/AIMS: Diagnostic evaluation of dementia for ethnic minority patients
      may be challenging. This study aimed to evaluate the quality of diagnostic
      evaluation of dementia for patients from ethnic minorities in Denmark. METHODS:
      The Danish national hospital registers were used to identify patients from the
      main ethnic minority groups in Denmark, who were diagnosed with dementia in the
      period 2005-2007. Three raters independently reviewed the patients' medical
      records. Data were compared to data from a previous similar study in the general
      Danish population. RESULTS: Fifty-seven medical records were reviewed. An
      acceptable diagnostic workup was documented in only 23% of the patients. Dementia
      diagnosis was confirmed in 35%. Significant differences in the quality of the
      diagnostic evaluation were found between patients from ethnic minorities and the
      general population. CONCLUSION: There are significant ethnic disparities in the
      quality of diagnostic evaluations and outcome of dementia in the secondary
      healthcare sector.

PMID- 21720164
TI  - Neuroendocrine pancreatic tumors are risk factors for pancreatic fistula after
      pancreatic surgery.
AB  - BACKGROUND: Postoperative pancreatic fistula (PF) is still regarded as a major
      complication in pancreatic surgery. In the present study, we evaluated the risk
      of PF in a large study population of patients with neuroendocrine pancreatic
      tumors (NPT), pancreatic cancer (PC), and chronic pancreatitis (CP). METHODS:
      Patients who underwent pancreatic surgery between 1989 and 2008 at our
      institution were retrospectively evaluated. Patients were analyzed regarding age,
      gender, BMI, alcohol, smoking, preoperative diabetes, reason for operation,
      operative procedure, and PF. Three different grades of PF (grades A, B, C) were
      defined. RESULTS: 133 patients with NPT, 212 patients with PC, 52 patients with
      CP, and 76 patients with other reasons were evaluated. Patients with a NPT had a
      significant higher risk of developing a PF than patients with PC, CP, or other
      reasons (p = 0.0001). Enucleation of the tumor was associated with the highest
      rate of PF (p = 0.001). In a multivariate analysis, BMI >26, and preoperative
      diabetes were associated with a higher rate of PF (p = 0.042 and p = 0.02,
      respectively). CONCLUSION: We demonstrated that after excluding factors like
      different definitions of PF, or different peri- or postoperative management,
      patients with NPT have a significantly higher risk of postoperative PF than
      patients with other pancreatic diseases.

PMID- 21720165
TI  - Priming with a combination of proangiogenic growth factors enhances wound healing
      in streptozotocin-induced diabetes in mice.
AB  - BACKGROUND: Numerous proangiogenic growth factors have been shown to improve
      impaired wound healing. This study evaluated the effects of subcutaneous
      pretreatment with a combination of proangiogenic growth factors on wound closure,
      mechanical properties, vessel density, and morphology. METHODS: Thirty-six Balb/c
      mice with streptozotocin-induced diabetes were divided into 3 groups. A mixture
      of VEGF (35.0 MUg), bFGF (2.5 MUg), and PDGF (3.5 MUg) was administered
      subcutaneously 3, 5, and 7 days prior to wounding in the first group, whereas the
      second group received three doses of 3.5 MUg PDGF. Wound sizes were assessed
      daily and the repaired tissues were harvested 7 days after wound closure.
      RESULTS: Complete closure (>=95% healing of initial wound area) was reached in
      all proangiogenic pretreated animals by day 17, whereas the PDGF monotherapy
      group needed up to 20 days for complete closure. By the time of tissue harvesting
      on day 24, complete closure was not reached in all control animals. Punch biopsy
      material revealed 1.6-fold higher vessel densities in the proangiogenic
      combination-pretreated group than in the controls. CONCLUSIONS: Proangiogenic
      priming revealed several significant effects on diabetic wound healing: faster
      time to closure, a higher vessel density, and improved functional outcome.

PMID- 21720166
TI  - Near-infrared fluorescence imaging in patients undergoing
      pancreaticoduodenectomy.
AB  - BACKGROUND: Intraoperative visualization of pancreatic tumors has the potential
      to improve radical resection rates. Intraoperative visualization of the common
      bile duct and bile duct anastomoses could be of added value. In this study, we
      explored the use of indocyanine green (ICG) for these applications and attempted
      to optimize injection timing and dose. METHODS: Eight patients undergoing a
      pancreaticoduodenectomy were injected intravenously with 5 or 10 mg ICG. During
      and after injection, the pancreas, tumor, common bile duct and surrounding organs
      were imaged in real time using the Mini-FLARETM near-infrared (NIR) imaging
      system. RESULTS: No clear tumor-to-pancreas contrast was observed, except for
      incidental contrast in 1 patient. The common bile duct was clearly visualized
      using NIR fluorescence, within 10 min after injection, with a maximal contrast
      between 30 and 90 min after injection. Patency of biliary anastomoses could be
      visualized due to biliary excretion of ICG. CONCLUSION: No useful tumor
      demarcation could be visualized in pancreatic cancer patients after intravenous
      injection of ICG. However, the common bile duct and biliary anastomoses were
      clearly visualized during the observation period. Therefore, these imaging
      strategies could be beneficial during biliary surgery in cases where the surgical
      anatomy is aberrant or difficult to identify.

PMID- 21720167
TI  - A syngeneic orthotopic murine model of pancreatic adenocarcinoma in the C57/BL6
      mouse using the Panc02 and 6606PDA cell lines.
AB  - BACKGROUND/AIMS: To develop a clinically relevant immunocompetent murine model to
      study pancreatic cancer using two different syngeneic pancreatic cancer cell
      lines and to assess MRI for its applicability in this model. METHODS: Two cell
      lines, 6606PDA and Panc02, were employed for the experiments. Cell proliferation
      and migration were monitored in vitro. MatrigelTM was tested for its role in
      tumor induction. Tumor cell growth was assessed after orthotopic injection of
      tumor cells into the pancreatic head of C57/BL6 mice by MRI and histology.
      RESULTS: Proliferation and migration of Panc02 were significantly faster than
      those of 6606PDA. Matrigel did not affect tumor growth/migration but prevented
      tumor cell spread after injection thus avoiding undesired peritoneal tumor
      growth. MRI could reliably monitor longitudinal tumor growth in both cell lines:
      Panc02 had a more irregular finger-like growth, and 6606PDA grew more
      spherically. Both tumors showed local invasiveness. Histologically, Panc02 showed
      a sarcoma-like undifferentiated growth pattern, whereas 6606PDA displayed a
      moderately differentiated glandular tumor growth. Panc02 mice had a significantly
      shorter (28 days) survival than 6606PDA mice (50 days). CONCLUSION: This model
      closely mimics human pancreatic cancer. MRI was invaluable for longitudinal
      monitoring of tumor growth thus reducing the number of mice required. Employing
      two different cell lines, this model can be used for various treatment and
      imaging studies.

PMID- 21720168
TI  - Component-resolved diagnostics: shedding light on the so-called 'squishy science'
      of food allergies?

PMID- 21720169
TI  - Latex medical gloves: time for a reappraisal.
AB  - Many hospitals have implemented policies to restrict or ban the use of devices
      made of natural rubber latex (NRL) in healthcare as precautionary measures
      against the perceived risk of NRL allergy. Changes in glove technology, progress
      in measuring the specific allergenic potential of gloves and a dramatic decrease
      in the prevalence of NRL allergies after interventions and education prompted us
      to revisit the basis for justifiable glove selection policies. The published
      Anglophone literature from 1990 to 2010 was reviewed for original articles and
      reviews dealing with the barrier and performance properties of NRL and synthetic
      gloves and the role of glove powder. The review shows that NRL medical gloves,
      when compared with synthetic gloves, tend to be stronger, more flexible and
      better accepted by clinicians. The introduction of powder-free gloves has been
      associated with reductions in protein content and associated allergies. Recently,
      new methods to quantify clinically relevant NRL allergens have enabled the
      identification of gloves with low allergenic potential. The use of low-protein,
      low-allergenic, powder-free gloves is associated with a significant decrease in
      the prevalence of type I allergic reactions to NRL among healthcare workers.
      Given the excellent barrier properties and operating characteristics,
      dramatically reduced incidences of allergic reactions, availability of specific
      tests for selection of low-allergen gloves, competitive costs and low
      environmental impact, the use of NRL gloves within the hospital environment
      warrants reappraisal.

PMID- 21720170
TI  - A single DH gene segment is sufficient for the establishment of an asthma
      phenotype in a murine model of allergic airway inflammation.
AB  - BACKGROUND: We have previously shown that the allergic sensitization to ovalbumin
      does not represent a superantigen-like immune response. In gene-targeted mice
      (DeltaD-iD) with a single modified Diversity gene segment (D(H)) of the
      immunoglobulin heavy chain, enriched for charged amino acids, the asthma
      phenotype in a murine model was markedly alleviated compared to wild-type
      animals. OBJECTIVE: We now sought to determine whether the confinement to a
      single D(H) gene segment alone leads to a reduced allergic phenotype. METHODS: We
      examined another gene-targeted mouse strain (DeltaD-DFL) with a single D(H) gene
      segment which encodes for neutral amino acids, thus reflecting the preferential
      repertoire in wild-type mice. Mice were sensitized intraperitoneally to
      ovalbumin. RESULTS: Despite the constraint to a single D(H) gene segment, DeltaD
      DFL mice mounted high total and allergen-specific IgG(1) and IgE serum levels
      after sensitization to ovalbumin. The affinity constants of allergen-specific
      IgG(1) antibodies did not differ between DeltaD-DFL and wild type. Following
      challenge with aerosolized allergen, a marked local T(H)2 cytokine response and
      an eosinophilic airway inflammation developed. Quantitative histology revealed
      increased mucus production and intense goblet cell metaplasia which were
      identical to those in wild type. Moreover, DeltaD-DFL mice developed an airway
      hyperreactivity to methacholine and to the specific allergen, which both did not
      differ from those in wild-type animals. CONCLUSION: A single D(H) gene segment is
      sufficient for the establishment of the asthma phenotype in a murine model of
      allergic airway inflammation. Thus, the allergic phenotype depends on the amino
      acid composition and not on the diversity of the classical antigen-binding site.

PMID- 21720171
TI  - Expression of a major plant allergen as membrane-anchored and secreted protein in
      human cells with preserved T cell and B cell epitopes.
AB  - BACKGROUND: Expression of allergens in human cells is a prerequisite for the
      development of antigen-specific cell therapy in IgE-mediated allergy. We
      developed a strategy how the clinically relevant major grass pollen allergen Phl
      p 5 can be efficiently secreted or expressed on the surface of human cells with
      preserved allergenic activity. METHODS: The cDNA of Phl p 5 was fused to a leader
      peptide with or without a transmembrane domain and both constructs were ligated
      into a mammalian expression vector. Transfection of these plasmids into human
      cells resulted in a membrane-anchored or secreted version of Phl p 5,
      respectively, as determined by ELISA or flow cytometric analysis. RESULTS: Both
      the secreted and membrane-anchored Phl p 5 proteins bound IgE from allergic
      patients in an immunoblot assay and induced specific histamine release and CD203c
      upregulation in basophils of grass pollen-allergic patients. Proliferation of
      peripheral blood mononuclear cells from Phl p 5-allergic individuals was induced
      upon stimulation with both variants of Phl p 5 expressed in human cells similar
      to recombinant Phl p 5. CONCLUSIONS: Secreted and membrane-anchored Phl p 5
      expressed in human cells preserved B cell as well as T cell epitopes and may be
      used to develop and test various cell-based strategies for allergen-specific
      immunomodulation and to delineate the tolerance mechanisms involved therein.

PMID- 21720172
TI  - Cloning, expression and patient IgE reactivity of recombinant Pru du 6, an 11S
      globulin from almond.
AB  - BACKGROUND: IgE-reactive proteins have been identified in almond; however, few
      have been cloned and tested for specific patient IgE reactivity. Here, we clone
      and express prunin 1 and prunin 2, isoforms of the major almond protein prunin,
      an 11S globulin, and assay each for IgE reactivity. METHODS: Prunin isoforms were
      PCR-amplified from an almond cDNA library, sequenced, cloned and expressed in
      Escherichia coli. Reactivity to the recombinant (r) allergens, Pru du 6.01 and
      Pru du 6.02, was screened by dot blot and immunoblot assays using sera from
      almond-allergic patients and murine monoclonal antibodies (mAbs). Sequential IgE
      binding epitopes were identified by solid-phase overlapping peptide analysis.
      Epitope stability was assessed by assaying denatured recombinant proteins by
      immunoblot. RESULTS: IgE reactivity to rPru du 6.01 and rPru du 6.02 was found in
      9 of 18 (50%) and 5 of 18 patients (28%), respectively. Four patients (22%)
      demonstrated reactivity to both isoforms. Murine anti-almond IgG mAbs also showed
      greater reactivity to rPru du 6.01 than to rPru du 6.02. Both stable and labile
      epitopes were detected. Six IgE-binding sequential epitope-bearing peptide
      segments on Pru du 6.01 and 8 on Pru du 6.02 were detected using pooled almond
      allergic sera. CONCLUSIONS: rPru du 6.01 is more widely recognized than rPru du
      6.02 in our patient population. The identification of multiple sequential
      epitopes and the observation that treatment with denaturing agents had little
      effect on IgE-binding intensity in some patients suggests an important role for
      sequential epitopes on prunins.

PMID- 21720173
TI  - Evaluation of IgE antibodies to recombinant peanut allergens in patients with
      reported reactions to peanut.
AB  - BACKGROUND: Peanut may cause severe reactions in allergic individuals. The
      objective was to evaluate IgE antibodies to various recombinant (r) peanut and
      birch pollen allergens in relation to IgE levels to whole peanut extract and
      severe allergic reactions to peanut. METHODS: Seventy-four Swedish peanut
      allergic patients (age: 14-61 years) reported previous peanut exposure and
      associated symptoms using a questionnaire. Their IgE reactivity to peanut, birch
      pollen and individual allergen components was analyzed using ImmunoCAP. RESULTS:
      Of the 48 subjects sensitized to Ara h 1, 2 or 3, 60% had peanut-specific IgE
      levels >15 kU(A)/l, while 100% of the subjects without detectable IgE to these
      allergens had low peanut-specific IgE levels (<10 kU(A)/l). The levels of IgE to
      rAra h 8, rBet v 1 and birch pollen were highly correlated (r(S) = 0.94, p <
      0.0001). Fifty-eight patients reported adverse reactions after accidental or
      deliberate peanut exposure (oral, inhalation or skin) of whom 41 had IgE to rAra
      h 1, 2 or 3. Symptoms of respiratory distress were associated with sensitization
      to Ara h 1, 2 or 3 (56 vs. 18%, p < 0.01). Two cases of anaphylaxis were reported
      among the individuals sensitized to Ara h 1-3. IgE to rAra h 8, rAra h 9,
      profilin or cross-reactive carbohydrate determinants were not associated with
      severe symptoms. CONCLUSIONS: The results indicate that IgE reactivity to Ara h
      1, 2 and 3 is associated with severe reactions after exposure to peanut in
      Swedish patients.

PMID- 21720174
TI  - Plant lipid transfer protein allergens: no cross-reactivity between those from
      foods and olive and Parietaria pollen.
AB  - BACKGROUND: Cross-reactivity among plant food allergens belonging to the
      nonspecific lipid transfer protein (LTP) family is well known. In contrast, the
      relationship among these allergens and their putative homologs from olive (Ole e
      7) and Parietaria (Par j 1) pollen has not been clarified. METHODS: Sera with
      specific IgE to LTP allergens were obtained from peach-, mustard- and olive
      pollen-allergic patients. Purified LTP allergens from foods (peach, apple,
      mustard and wheat) and pollens (olive, mugwort and Parietaria) were tested by
      ELISA and ELISA-inhibition assays. RESULTS: Plant food LTP-allergic patients
      showed a significantly higher number of sera (89-100 vs. 33-64%) with specific
      IgE and mean specific IgE levels (0.30-1.56 vs. 0.21-0.34 OD units) to the 4 food
      LTP allergens tested than to olive Ole e 7 and Parietaria Par j 1 pollen. ELISA
      inhibition assays indicated cross-inhibition between food LTP allergens but no
      cross-reactivity between these allergens and Ole e 7 and Par j 1, or, even more,
      between the LTP allergens from olive and Parietaria pollen. CONCLUSIONS: LTP
      allergens from olive and Parietaria pollen cross-react neither with allergenic
      LTPs from plant foods nor between themselves. Therefore, both pollens do not seem
      to be related with the LTP syndrome.

PMID- 21720175
TI  - Microarray gene analysis of Toll-like receptor signaling elements in chronic
      rhinosinusitis with nasal polyps.
AB  - OBJECTIVE: To identify the regulatory mechanisms of Toll-like receptor (TLR)
      associated genes in chronic rhinosinusitis (CRS) with nasal polyps (NP) using
      gene microarray analyses. METHODS: We pooled: (1) NP biopsy specimens from 10
      nonatopic CRS patients and (2) healthy mucosal tissue from 10 additional
      nonatopic healthy patients (controls). These pooled samples were evaluated by
      gene microarrays that included 125 genes for TLRs and associated signaling
      elements. To validate gene product expressions, 20 NP and 15 normal nasal
      turbinate tissues were evaluated for TLR-9 expression by immunohistochemical
      staining and Western blots using samples from gland cells, epithelial cells, and
      mononuclear cells cytologically identified by HE staining. RESULTS: In pooled NP
      samples compared to pooled controls, 4 genes were upregulated (>= 2-fold higher
      expression) and 19 were downregulated (<= 0.5-fold lower expression). TLR-9 was
      an upregulated gene in NP tissue. Compared to control tissue, there were
      significantly higher percentages of TLR-9 positively stained NP gland cells,
      epithelial cells, and mononuclear cells (p < 0.001). On Western blots, while both
      normal and NP tissues expressed TLR-9 protein, the expression was significantly
      more pronounced for NP tissue (p < 0.001). CONCLUSIONS: Inflammation associated
      with CRS may be due to dysregulated innate immune elements, particularly TLR-9
      and its associated signal transduction elements, which may impact upon prolonged
      activation of adaptive immune responses in the sinonasal mucosa.

PMID- 21720176
TI  - Lack of transient receptor potential vanilloid-1 enhances Th2-biased immune
      response of the airways in mice receiving intranasal, but not intraperitoneal,
      sensitization.
AB  - BACKGROUND: Transient receptor potential vanilloid-1 (TRPV1) may modulate
      allergic airway inflammation because it is expressed not only on the nerve
      endings but also on several cells of the immune system. We wanted to know the
      characteristics of airway and systemic responses against sensitization and
      challenge with allergens in TRPV1 receptor gene knockout mice (TRPV1(-/-)).
      METHODS: TRPV1(-/-) and their wild-type counterparts (TRPV1(+/+)) were sensitized
      with either house dust mite (HDM) or ovalbumin (OVA) via intranasal (i.n.) or
      intraperitoneal (i.p.) route before the final i.n. challenge with the
      corresponding allergen. One day after the final challenge, serum IgE levels,
      cytokine levels in the bronchoalveolar lavage fluid (BALF), and the number of
      BALF cells were examined after measuring bronchial hyperresponsiveness against
      methacholine. RESULTS: Compared to TRPV1(+/+), TRPV1(-/-) showed enhanced Th2
      biased response after i.n. HDM or OVA sensitization, including increased levels
      of serum IgE, interleukin 4 (IL-4) and eosinophils in the BALF. By contrast, when
      sensitized via i.p. route, the response against OVA or HDM was almost similar
      between TRPV1(+/+) and TRPV1(-/-). CONCLUSION: TRPV1 receptor may downregulate
      Th2-biased immune response when sensitized via airways, although this was not the
      case when sensitized systemically.

PMID- 21720177
TI  - Malignancy and specific allergen immunotherapy: the results of a case series.
AB  - BACKGROUND: Specific immunotherapy with allergen is the only causative treatment
      for IgE-mediated allergies such as stinging insect allergy or hay fever and works
      by the induction of blocking antibodies and regulatory T lymphocytes. OBJECTIVE:
      Does a hypothetical obstruction of tumor surveillance presupposing the induction
      of regulatory T cells really justify detaining immunotherapy to oncologic
      patients as suggested by recent guidelines? METHODS: We report 6 patients (4
      female, 2 male) suffering or having suffered from stage 1 cancer (4 melanomas, 1
      lung cancer, 1 breast cancer) and concomitant IgE-mediated allergy. Four of them
      had a history of severe anaphylactic reactions to the insect yellow jacket, the
      5th suffered from allergic rhinoconjunctivitis to dust mites, and the 6th to
      grass/rye pollen. RESULTS: Between 2004 and 2010, subcutaneous immunotherapy was
      safely performed in 5 patients without signs of tumor reactivation. The cancer in
      2 of them was diagnosed immediately after specific immunotherapy had been
      initiated and in another 2 the active cancer phase had already finished years
      before; the 5th suffered from a relapse around the time of the initiation of
      immunotherapy. At the time of the writing of the manuscript, 4 of them had
      already concluded 3 years of treatment, another one almost 1 year. The melanoma
      in the 6th patient was diagnosed 5 months after reaching the maintenance dose.
      Immunotherapy with grass/rye pollen was aborted in this patient based on current
      guidelines. CONCLUSIONS: Specific immunotherapy was safely administered in
      patients suffering concomitantly from IgE-mediated allergy and lower stage
      cancer.

PMID- 21720178
TI  - Hypersensitivity reactions to docetaxel: retrospective evaluation and development
      of a desensitization protocol.
AB  - BACKGROUND: Docetaxel (DT) is an extensively used taxane, frequently associated
      with hypersensitivity reactions. The aim of this study was to record the
      epidemiological and clinical features of hypersensitivity to DT in non-small cell
      lung cancer patients in order to obtain useful information concerning the
      management of these patients. We also developed a desensitization protocol and
      evaluated its clinical application. METHODS: We retrospectively reviewed records
      of 620 non-small cell lung cancer patients treated with DT-containing regimens in
      the adjuvant, first-, second- or next-line setting. Data from 102 patients who
      had exhibited hypersensitivity reactions were analyzed according to the Common
      Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for
      the desensitization protocol. We applied the standard protocol for parenteral
      desensitization to beta-lactam antibiotics, and DT treatment was carried out with
      a series of 10-fold dilutions in sufficient volume to administer the total dose.
      RESULTS: One hundred and two patients (16.5%) were recorded as having
      hypersensitivity to DT. Reactions were observed after approximately 2.5 +/- 1.0
      cycles. Only 14 patients (14/620, 2%) developed grade 3-4 hypersensitivity.
      Reactions were more likely in patients during second- or third-line chemotherapy,
      but no other correlation (age, gender, atopic status) was observed. Five patients
      completed a parenteral desensitization protocol and continued their treatment
      uneventfully. CONCLUSIONS: Hypersensitivity reactions to DT respond quickly to
      discontinuation along with appropriate supportive care. Premedication and
      increased infusion time may allow readministration. The desensitization protocol
      that we developed provides a reliable alternative to permanent discontinuation of
      DT.

PMID- 21720179
TI  - Faecal microbiota and short-chain fatty acid levels in faeces from infants with
      cow's milk protein allergy.
AB  - BACKGROUND: The present study was designed to compare the faecal microbiota and
      concentrations of faecal short-chain fatty acid and ammonia between healthy and
      cow's milk protein allergic (CMPA) infants. METHODS: The population comprised 92
      infants aged 2-12 months who were nonallergic (n = 46) or diagnosed as having
      CMPA (n = 46). Faecal samples were analyzed by fluorescent in situ hybridization
      and flow cytometry, using a panel of 10 rRNA targeted group- and species-specific
      oligonucleotide probes. Acetic, propionic, butyric, isocaproic and branched-chain
      short fatty acids (BCSFA) were measured by gas-liquid chromatography, lactate by
      enzymatic reaction, and pH and ammonia levels were determined. RESULTS: CMPA
      infant faeces had significantly higher proportions of the Clostridium coccoides
      group and Atopobium cluster and a higher sum of the proportions of the different
      bacterial groups in comparison to healthy infant faeces. Faecal pH and ammonia
      did not significantly differ between CMPA and healthy infants. Faeces
      concentrations and percentages of butyric acid and BCSFA were higher in CMPA
      infants than in healthy infants. CONCLUSIONS: The findings clearly set a link
      between a dysbiosis in gut microbiota composition and the pathogenesis of CMPA.
      No single species or genus appeared to play an essential role, but dysbiosis led
      to biomarkers of CMPA among bacterial fermentation products.

PMID- 21720180
TI  - Patients' satisfaction with diagnostic drug provocation tests and perception of
      its usefulness.
AB  - BACKGROUND AND AIM: Although still controversial, drug provocation tests (DPTs)
      are considered by many as the gold standard for diagnosis of drug
      hypersensitivity. No studies have addressed the opinion of patients submitted to
      DPT. We aimed to determine patient satisfaction with diagnostic DPT and their
      perception of its usefulness. METHODS: Surveys were supplied to patients
      submitted to diagnostic DPT in 3 different drug allergy clinics which used the
      same diagnostic protocols for drug hypersensitivity evaluation. Seventy-three
      patients (33.6%) were enrolled in Porto (Portugal), 102 (47%) in Montpellier
      (France) and 42 (19.4%) in Vilnius (Lithuania). The patients filled in a written
      questionnaire within 15 days after the diagnostic procedure, and satisfaction was
      assessed on a 1 (very unsatisfied) to 5 (very satisfied) score. RESULTS: A total
      of 217 surveys were collected; 144 female patients (66.4%). The most prevalent
      studied reactions were cutaneous (70.1%), but 17.9% of the patients had had a
      systemic reaction. beta-Lactam antibiotics were the main culprit drugs (44.3%)
      tested in all centres and 25.3% of the patients had a positive DPT. No patients
      were unsatisfied (8.8% were neither unsatisfied nor satisfied and the others were
      satisfied or very satisfied). The level of satisfaction did not depend on the
      results of the DPT; 207 (95.4%) believed DPTs were useful and almost all the
      patients would recommend DPTs to others. CONCLUSIONS: Most patients were
      satisfied with DPT for diagnostic purposes. Satisfaction with the procedure was
      independent of the results of the provocation tests and did not depend on the
      country.

PMID- 21720181
TI  - Protective and risk factors for allergic diseases in high-risk children at the
      ages of two and five years.
AB  - BACKGROUND: Environmental and lifestyle factors such as breast-feeding and pets
      seem to affect atopic disease prevalence. We identified risk factors for allergic
      diseases. METHODS: We prospectively followed until the age of 5 years a cohort of
      1,223 children born into allergic families, who participated in a randomized
      placebo-controlled trial of probiotics as preventive against allergic disease. We
      evaluated the cumulative incidence of allergic diseases with questionnaires and
      examined all children at the ages of 2 and 5 years. RESULTS: Compared to allergy
      in one parent only, allergy in both parents conferred an increased risk of
      allergic disease at the ages of 2 (OR 1.64; 95% CI 1.11-2.42, p = 0.013) and 5
      (OR 1.83; 95% CI 1.24-2.70, p = 0.002) and at the age of 2 for eczema (OR 1.74;
      95% CI 1.17-2.58, p = 0.006). Exclusive breast-feeding over 2 months elevated the
      risk of eczema at the ages of 2 (OR 1.73; 95% CI 1.15-2.61, p = 0.009) and 5 (OR
      1.51; 95% CI 1.03-2.23, p = 0.036). Cat or dog exposure at 0-2 years and at 0-5
      years protected against IgE sensitization until 5 years of age (OR 0.60; 95% CI
      0.37-1.00, p = 0.048, and OR 0.61; 95% CI 0.39-0.96, p = 0.033), and exposure at
      the ages of 0-5 years protected against allergic rhinitis until the age of 5 (OR
      0.46; 95% CI 0.25-0.85, p = 0.013) in the probiotic group. CONCLUSIONS: Allergy
      in both parents is an independent predictor of eczema and of allergic disease
      until the ages of 2 and 5. Long, exclusive breast-feeding was associated with
      increased eczema at the ages of 2 and 5, and cat or dog exposure was associated
      with decreased IgE sensitization and allergic rhinitis in the probiotic group.

PMID- 21720182
TI  - Certain imidazotetrazines escape O6-methylguanine-DNA methyltransferase and
      mismatch repair.
AB  - Resistance to temozolomide (TMZ), conferred by O6-methylguanine-DNA
      methyltransferase (MGMT) or mismatch repair (MMR) deficiency, presents obstacles
      to successful glioblastoma multiforme (GBM) treatment. Activities of novel TMZ
      analogs, designed to overcome resistance, were tested against isogenic SNB19 and
      U373 GBM cell lines (V = vector control, low MGMT; M = MGMT overexpression). TMZ
      and triazene MTIC demonstrated >9-fold resistance in SNB19M cells (cf SNB19V). N
      3 methyl ester analog 11 and corresponding triazene 12 inhibited growth of TMZ
      sensitive (V) and TMZ-resistant (M) cells (GI(50) <50 MUM). Ethyl ester 13 and
      triazene 14 gave similar profiles. MMR-deficient colorectal carcinoma cells,
      resistant to TMZ (GI(50) >500 MUM), responded to analog 11 and 13 treatment.
      Cross-resistance to these agents was not observed in cell lines possessing
      acquired TMZ resistance (SNB19VR; U373VR). Methyl ester 11 blocked SNB19V, SNB19M
      and SNB19VR cells in S and G(2)/M, causing dose- and time-dependent apoptosis.
      DNA damage, recruiting excision repair was detected by alkaline comet assay; H2AX
      phosphorylation indicated a lethal DNA double-strand break formation following
      analog 11 exposure. Compounds 11 and 13 demonstrated 3.7- and 5.1-fold enhanced
      activity in base excision repair-deficient Chinese hamster ovary cells;
      furthermore, poly (ADP-ribose) polymerase-1 inhibition potentiated HCT-116 cells'
      sensitivity to analog 11. In conclusion, analogs 11 and 13 exert anticancer
      activity irrespective of MGMT and MMR.

PMID- 21720183
TI  - Adjuvant chemotherapy for small bowel adenocarcinoma after curative surgery.
AB  - OBJECTIVES: We evaluated prognostic factors affecting relapse-free survival (RFS)
      and overall survival (OS), and investigated the role of adjuvant chemotherapy in
      patients with small bowel adenocarcinoma (SBA). METHODS: Data from 52 patients
      with SBA who underwent curative surgery at the Asan Medical Center between
      January 1989 and December 2009 were retrospectively analyzed. Patients were
      divided into two groups: those who did (n = 23) and did not (n = 29) receive
      adjuvant chemotherapy. RESULTS: At a median follow-up of 32.2 months (range, 5.5
      212.2 months), relapses had occurred in 17 patients (32.7%), with a 5-year RFS
      rate of 52.9% (95% CI, 39.3-66.5%), and 19 patients (36.5%) had died, with a 5
      year OS rate of 59.0% (95% CI, 45.6-72.4%). The most frequent sites of relapse
      were the peritoneum and liver. Multivariate analysis showed that lymph node
      involvement was the only factor independently associated with poor RFS and OS.
      After inverse probability of treatment weighting adjustment, adjuvant
      chemotherapy did not enhance RFS [hazard ratio (HR), 1.399; 95% CI, 0.498-3.933]
      or OS (HR 0.797; 95% CI, 0.307-2.068). CONCLUSIONS: Lymph node involvement is a
      predictor of poor prognosis in patients with SBA who undergo curative surgery.

PMID- 21720184
TI  - Combination of gemcitabine and doxorubicin in rapidly progressive metastatic
      renal cell carcinoma and/or sarcomatoid renal cell carcinoma.
AB  - BACKGROUND/AIMS: Metastatic renal cell carcinoma (mRCC) can be rapidly
      progressive when tumors exhibit sarcomatoid or Fuhrman grade 4 features. Efficacy
      of gemcitabine (Gem) with doxorubicin (Dox) in sarcomatoid or rapidly progressive
      mRCC has been reported. We retrospectively evaluated Gem + Dox in a consecutive
      cohort of this particular patient population. PATIENTS AND METHODS: Patients had
      an Eastern Cooperative Oncology Group performance status of 2 or more and rapidly
      progressive mRCC or mRCC with sarcomatoid features. Gem (1,500 mg/m(2)) and Dox
      (50 mg/m(2)) were given every 2 weeks with granulocyte colony-stimulating factor.
      RESULTS: Twenty-nine patients were treated. Sarcomatoid features were predominant
      in 6 patients, while 14 tumors were Fuhrman grade 4. All patients had progressive
      mRCC within 4 months. No grade 4 toxicity or drug-related death was reported. One
      partial response (7 months), 1 mixed response, and 14 stable diseases (>=4 months
      for 9 patients) were observed and no response was seen in sarcomatoid tumors. The
      median disease-free survival was 3.7 months (>=6 months for 8 patients) and the
      median overall survival was 4.8 months (>12 months for 5 patients). CONCLUSION:
      This study showed a lower response rate than previously reported. Nevertheless,
      some patients had prolonged survival outcomes. This combination could be an
      option in sarcomatoid histology (NCCN guidelines) or rapidly progressive disease,
      but this population represents an unmet medical need.

PMID- 21720185
TI  - Extended-spectrum beta-lactamase-mediated resistance among bacterial isolates
      recovered from ocular infections.
AB  - PURPOSE: To evaluate resistances mediated by extended-spectrum beta-lactamases
      (ESBLs) and AmpC beta-lactamases among Gram-negative bacteria recovered from
      ocular infections. METHODS: As per the Clinical Laboratory Standards Institute
      M100-S-16 document, a total of 135 Gram-negative bacilli were recovered from
      ocular specimens and were subjected to phenotypic confirmation for ESBL
      production by the double-disc synergy test, cephalosporin and clavulanate
      combination disc test and E test, and, for AmpC beta-lactamase, the modified
      double-disc approximation method and AmpC disc test. RESULTS: In the double-disc
      synergy test, 21 (15.5%) isolates showed positive results against the cefpodoxime
      disc, 19 (14%) against cefpodoxime and cefotaxime, 15 (11%) against cefpodoxime,
      cefotaxime and ceftriaxone and 10 (7%) isolates were against cefpodoxime,
      cefotaxime, ceftriaxone and ceftazidime discs. In the cephalosporin/clavulanate
      combination disc test, 19 (14%) isolates showed positive results against
      cefotaxime with clavulanic acid and 10 (7%) isolates against ceftazidime with
      clavulanic acid. In the E test, 10 (7%) isolates displayed positive results
      against ceftazidime and 19 (14%) against cefotaxime. In the AmpC disc test for
      phenotypic confirmation, indentations were observed in 15 (11%) isolates with
      flattening also occurring in 10 (7%) isolates. CONCLUSION: The incidences of ESBL
      and AmpC beta-lactamase-mediated resistances are found to be 7 and 18.5% among
      ocular isolates, respectively, and are more prevalent among the strains of
      Escherichia coli and Klebsiella pneumoniae.

PMID- 21720187
TI  - Biomechanical and morphological differences between the sclera canal ring and a
      peripheral sclera ring in the porcine eye.
AB  - AIM: To investigate a possible association between the biomechanical load and
      unload behaviour and the elastin content of the sclera canal ring (SCR) and a
      superiorly localized sclera ring (SPS) in the porcine eye. METHODS: Two sclera
      rings were trephined from each of 40 porcine eyes, one containing the SCR and the
      other an SPS. The load and the unload curves were measured in the extension range
      of 0-2.0 mm by a biomaterial tester. Hysteresis was determined from the area
      enclosed by the loading and unloading curve. Histochemical staining with resorcin
      fuchsin and morphometric analysis of paraffin-embedded sections of both rings
      were performed to detect the area occupied by elastin fibres. RESULTS: At 1 mm
      extension, the mean load of the SCR was 0.89 +/- 0.22 N and that of the SPS 1.13
      +/- 0.19 N, which was not significantly different between both rings (p > 0.05).
      Mean hysteresis in the SCR was 1.55 +/- 0.30 N * mm and 1.90 +/- 0.18 N * mm in
      the SPS, which was significantly different between both rings (p = 0.01). Mean
      sclera thickness was 986 MUm in the SCR (range: 900-1,060 MUm) and 971 MUm in the
      SPS (range: 800-1,200 MUm) without a statistically significant difference between
      both sclera rings (p = 0.78). The area occupied by elastin fibres was 15.5 +/-
      3.4% in the SCR and 4.5 +/- 1.5% in the SPS, which was significantly different
      between both rings (p = 0.0001). CONCLUSION: Hysteresis in the SCR was
      significantly lower than in the SPS, indicating a higher elasticity of the SCR in
      the porcine eye. This effect could be explained by a higher content of elastin in
      the surrounding ring of the peripapillary optic nerve head providing reversible
      contraction in cases of intra-ocular pressure variations.

PMID- 21720188
TI  - Peripheral control of inflammatory but not neuropathic pain by endogenous
      cholinergic system.
AB  - This study investigated the role of the cholinergic system in the modulation of
      inflammatory and neuropathic pain. The paw pressure test was used with
      inflammatory pain induced by intraplantar injection of carrageenan and
      neuropathic pain induced by sciatic nerve constriction. All drugs were locally
      administered into the right hindpaw of rats. Neostigmine, an acetylcholinesterase
      inhibitor (2, 4, 8 or 16 MUg), inhibited the inflammatory pain induced by
      carrageenan (250 MUg/paw), but not the hyperalgesia induced by prostaglandin E2
      (2 MUg/paw). Neostigmine (8 MUg) increased the nociceptive threshold only in the
      treated paw, suggesting only a local effect. The muscarinic antagonist atropine
      (150, 300 and 600 MUg) caused a reduction in the nociceptive threshold induced by
      carrageenan (125 MUg/paw), but not by prostaglandin E2 (1 MUg/paw). Atropine
      significantly decreased the nociceptive threshold only in the treated paw. On the
      other hand, in the presence of neuropathic pain, atropine (300 MUg) did not alter
      the nociceptive threshold induced by constriction of the sciatic nerve. This
      study suggests that a peripheral endogenous cholinergic system involving
      muscarinic receptors may be activated during inflammation as a modulatory
      negative feedback control of inflammatory pain.

PMID- 21720189
TI  - HTDP-2, a new synthetic compound, inhibits glutamate release through reduction of
      voltage-dependent Ca2+ influx in rat cerebral cortex nerve terminals.
AB  - AIM: The present study was aimed at investigating the effect of trans-6-(4
      chlorobutyl)-5-hydroxy-4-(phenylthio)-1-tosyl-5,6-dihydropyridine-2(1H)-one (HTDP
      2), a novel synthetic compound, on the release of endogenous glutamate in rat
      cerebrocortical nerve terminals (synaptosomes) and exploring the possible
      mechanism. METHODS: The release of glutamate was evoked by the K+ channel blocker
      4-aminopyridine (4-AP) and measured by an on-line enzyme-coupled fluorimetric
      assay. We also used a membrane potential-sensitive dye to assay nerve terminal
      excitability and depolarization, and a Ca2+ indicator, Fura-2-acetoxymethyl
      ester, to monitor cytosolic Ca2+ concentrations ([Ca2+](c)). RESULTS: HTDP-2
      inhibited the release of glutamate evoked by 4-AP in a concentration-dependent
      manner. Inhibition of glutamate release by HTDP-2 was prevented by the chelating
      intraterminal Ca2+ ions, and by the vesicular transporter inhibitor bafilomycin
      A1, but was insensitive to the glutamate transporter inhibitor DL-threo-beta
      benzyloxyaspartate. HTDP-2 did not alter the resting synaptosomal membrane
      potential or 4-AP-mediated depolarization whereas it decreased the 4-AP-induced
      increase in [Ca2+](c). Furthermore, the inhibitory effect of HTDP-2 on the evoked
      glutamate release was abolished by the N-, and P/Q-type Ca2+ channel blocker
      omega-conotoxin MVIIC, but not by the ryanodine receptor blocker dantrolene, or
      the mitochondrial Na+/Ca2+ exchanger blocker CGP37157. CONCLUSION: Based on these
      results, we suggest that, in rat cerebrocortical nerve terminals, HTDP-2
      decreases voltage-dependent Ca2+ channel activity and, in so doing, inhibits the
      evoked glutamate release.

PMID- 21720190
TI  - Music therapy or music medicine?

PMID- 21720192
TI  - Episodic rage associated with primary aldosteronism resolved with adrenalectomy.

PMID- 21720193
TI  - Prevalence of postural orthostatic tachycardia syndrome in patients with
      psychiatric disorders.

PMID- 21720194
TI  - Potential role of brain-derived neurotrophic factor in omega-3 Fatty Acid
      supplementation to prevent posttraumatic distress after accidental injury: an
      open-label pilot study.

PMID- 21720195
TI  - Treating chronic symptoms of depression in the virtual clinic: findings on
      chronicity of depression in patients treated with internet-based computerized
      cognitive behaviour therapy for depression.

PMID- 21720196
TI  - Aspirin adherence, depression and one-year prognosis after acute coronary
      syndrome.

PMID- 21720197
TI  - Major depression and avoidant personality traits in eating disorders.

PMID- 21720198
TI  - The prediction of psychotherapy success by outcome expectations in inpatient
      psychotherapy.

PMID- 21720199
TI  - Therapeutic monoclonal antibodies.
AB  - Over a hundred years has passed since the discovery of the "magic bullet" serum
      therapy by Kitasato and Behring, the first ever therapeutic use of antibodies.
      More than 80 years later, the investigation of immunoglobulin structure and
      function and the development of cell and molecular biology introduced the
      production of monoclonal antibodies (MoAbs). In the 35 years since the first
      process for creating MoAbs was introduced, they have remained the centerpiece of
      the growing biotechnology and pharmaceutical industry. Herein, I review the
      history, development, and clinical settings of therapeutic MoAbs that have had a
      significant impact on life-saving medicine.

PMID- 21720200
TI  - Role of transcription factors in differentiation and reprogramming of
      hematopoietic cells.
AB  - Differentiation of hematopoietic cells is a sequential process of cell fate
      decision originating from hematopoietic stem cells (HSCs), allowing multi- or
      oligopotent progenitors to commit to certain lineages. HSCs are cells that are
      able to self-renew and repopulate the marrow for the long term. They first
      differentiate into multipotent progenitors (MPPs), which give rise to common
      lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). CMPs then
      differentiate into granulocyte monocyte progenitors (GMPs) and megakaryocyte
      erythroid progenitors (MEPs), which are the precursors of granulocytes/monocytes
      and erythrocytes/megakaryocytes, respectively. Lineage specification at
      differentiation branch points is dictated by the activation of lineage-specific
      transcription factors such as C/EBPalpha, PU.1, and GATA-1. The role of these
      transcription factors is generally instructive, and the expression of a single
      factor can often determine cell fate. Differentiation was long regarded as an
      irreversible process, and it was believed that somatic cells would not change
      their fate once they were differentiated. This paradigm was first challenged by
      the finding that ectopic cytokine signals could change the fate of
      differentiation, probably through modulating internal transcription networks.
      Subsequently, we and others showed that virtually all progenitors, including
      CLPs, CMPs, GMPs, and MEPs, still retain differentiation plasticity, and they can
      be converted into lineages other than their own by ectopic activation of only a
      single lineage-specific transcription factor. These findings established a novel
      paradigm for cellular differentiation and opened up an avenue for artificially
      manipulating cell fate for clinical use.

PMID- 21720201
TI  - Intracranial germ cell tumors: efficacy of neoadjuvant chemo-radiotherapy without
      surgical biopsy.
AB  - In this report, we review 41 patients with intracranial germ cell tumors (GCTs)
      treated at the Department of Neurosurgery, Keio University School of Medicine, in
      the 25-year period between January 1982 and July 2006. The main aim of the
      present study was to compare the effectiveness of our current intracranial GCT
      management protocol, comprising neoadjuvant chemo-radiotherapy without surgical
      biopsy of tumors as far as possible, to that of historical controls. In all
      patients, charts were reviewed and tumor and patient characteristics, including
      age, sex, type of tumor marker secreted, treatment protocol, and clinical
      outcomes, were compared. The relationship between these variables was analyzed by
      means of the Cox proportional hazards model. Thus far, four patients treated by
      approaches other than the current protocol have died of their tumor. The overall
      5-, 10-, and 15-year survival rates of all the patients calculated by the Kaplan
      Meier method were 91.9%, 88.6%, and 88.6%, respectively. According to the results
      of the Cox proportional hazards model, patients with secreting GCTs show
      statistically poorer prognoses than those with non-secreting GCTs (P = 0.0073),
      and although not statistically significant, patients treated with our current
      protocol tend to show better prognoses than historical controls (P = 0.0543). All
      five patients with secreting GCT treated using our current protocol are still
      alive after an average follow-up period exceeding 7 years, and only one of these
      has shown tumor recurrence. With our current treatment protocol comprising
      neoadjuvant chemo-radiotherapy without surgical biopsy, prognoses of patients
      with GCTs have improved compared to historical controls at our institution.

PMID- 21720202
TI  - Pathogenesis of gastritis in ileitis-prone SAMP1/Yit mice.
AB  - Inflammatory bowel disease is a chronic inflammatory disease of the gut which
      manifests as ulcerative colitis or Crohn's disease. One of the most studied
      animal models of spontaneous Crohn's disease is the senescence-accelerated mouse
      (SAMP1/Yit strain) model. In SAMP1/Yit mice, although many immunological
      responses are perturbed, some evidence suggests that the primary defect lies in
      the epithelial cell barrier. In the process of studying epithelial permeability,
      we observed that the stomach in SAMP1/Yit mice also had increased permeability.
      Upon further examination, these mice were shown to have marked, chronic gastritis
      with focal to diffuse aggregates of mononuclear cells of mixed lineages. These
      aggregates were located predominantly in the oxyntic mucosa, with occasional
      lesions in the forestomach but with relatively fewer cellular infiltrates in the
      antral mucosa. Real-time RT PCR showed an increase in several helper T cell (Th
      cell)-derived pro-inflammatory cytokines in the gastric mucosa of SAMP1/Yit mice.
      However, many of the cells in the aggregates of SAMP1/Yit mice were B cells.
      SAMP1/Yit B cells exacerbate ileitis when co-transferred into immunodeficient
      recipients. The gastritis also reflects a contribution by B cells. As SAMP1/Yit
      mice were derived from AKR mice, we examined AKR mice and determined that they
      too have an increased occurrence of gastritis, although they do not develop
      ileitis. B cells contributed to the gastric inflammation in these mice also.
      Thus, SAMP1/Yit mice display gastritis as well as ileitis, and B cells appear to
      play a role in the pathogenesis of inflammation at both sites. This review will
      discuss some of the mechanisms that may account for these different
      manifestations of gastrointestinal disease.

PMID- 21720203
TI  - Dysexecutive performance of healthy oldest old subjects on the Frontal Assessment
      Battery.
AB  - BACKGROUND AND AIMS: Frontal lobes and executive functions appear to be more
      vulnerable to normal aging than other cerebral regions and domains. The aim of
      the study was to evaluate executive functions by the Frontal Assessment Battery
      (FAB) in healthy oldest old subjects free of dementia. METHODS: Thirty-two
      healthy oldest old subjects (age range 85-97 yrs) and 32 young old subjects (aged
      61-74 yrs) were studied. All subjects were living with their families or alone
      and were considered normal, since they were fully independent in their activities
      of daily living and without signs or symptoms characteristic of any type of
      dementia. Mental status was assessed by the Mini- Mental State Examination (MMSE)
      and executive functions by the FAB. RESULTS: Mean MMSE scores were 23.12 +/- 4.68
      in oldest old and 26.78 +/- 2.60 in young old subjects (p<0.005). Delayed recall
      was the most impaired domain, followed by executive (Serial 7). Mean FAB scores
      were 9.37 +/- 4.14 in the oldest old and 13.53 +/- 2.12 in the young old
      (p<0.0001). Among the FAB subtests, conceptualization was the most impaired in
      both groups, with sensitivity to interference and inhibitory control exhibiting
      higher discrimination between the oldest old and young old. Education influenced
      performance on MMSE and FAB in both groups. CONCLUSIONS: On the FAB test, healthy
      oldest old subjects showed executive impairment with respect to the young olds,
      due to the involvement of functions depending on activities of different regions
      of the frontal lobes. FAB results were consistent with the hypothesis that
      frontal lobes have a high vulnerability to normal aging. Short composite
      batteries like the FAB are suitable for rapid and reliable description of
      patterns of executive functioning in the oldest old.

PMID- 21720205
TI  - Chronic sleep deprivation and seasonality: implications for the obesity epidemic.
AB  - Sleep duration has progressively fallen over the last 100 years while obesity has
      increased in the past 30 years. Several studies have reported an association
      between chronic sleep deprivation and long-term weight gain. Increased energy
      intake due to sleep loss has been listed as the main mechanism. The consequences
      of chronic sleep deprivation on energy expenditure have not been fully explored.
      Sleep, body weight, mood and behavior are subjected to circannual changes.
      However, in our modern environment seasonal changes in light and ambient
      temperature are attenuated. Seasonality, defined as cyclic changes in mood and
      behavior, is a stable personality trait with a strong genetic component. We
      hypothesize that the attenuation in seasonal changes in the environment may
      produce negative consequences, especially in individuals more predisposed to
      seasonality, such as women. Seasonal affective disorder, a condition more common
      in women and characterized by depressed mood, hypersomnia, weight gain, and
      carbohydrate craving during the winter, represents an extreme example of
      seasonality. One of the postulated functions of sleep is energy preservation.
      Hibernation, a phenomenon characterized by decreased energy expenditure and
      changes in the state of arousal, may offer useful insight into the mechanisms
      behind energy preservation during sleep. The goals of this article are to: a)
      consider the contribution of changes in energy expenditure to the weight gain due
      to sleep loss; b) review the phenomena of seasonality, hibernation, and their
      neuroendocrine mechanisms as they relate to sleep, energy expenditure, and body
      weight regulation.

PMID- 21720206
TI  - Hypogonadism and metabolic syndrome.
AB  - BACKGROUND: The relationship between metabolic syndrome (MetS), male hypogonadism
      and their possible interaction in cardiovascular (CV) risk stratification are not
      completely understood. AIM: We reviewed relationships between testosterone (T)
      and MetS emphasizing their possible interaction in the pathogenesis of CV
      diseases. MATERIALS AND METHODS: A systematic search of published evidence was
      performed using Medline (1969 to January 2011). RESULTS: Cross-sectional data
      have shown that subjects with MetS have lower levels of total T (TT) (about 3
      nmol/l), as hypogonadism is more evident in subjects with than in those without
      erectile dysfunction (ED) than in those without. Longitudinal evidence shows that
      low T is allocated with a higher risk of subsequent development of MetS, although
      the reverse condition is also possible. Which are the factors in MetS responsible
      for the low T is not completely clarified. In clinical studies, increased waist
      circumference is the major determinant of MetS-associated hypogonadism. Our
      experiments in rabbits do not support the idea that visceral fat is the main
      determinant of MetS-associated male hypogonadism. Only few randomized clinical
      trials have evaluated the impact of T replacement therapy (TRT) in patients with
      MetS. Available evidence suggests that TRT decreases visceral fat accumulation
      and ameliorates insulin sensitivity, whereas androgen deprivation increases
      abdominal adiposity. CONCLUSIONS: The clinical significance of the MetS
      associated hypogonadism needs further clarifications. In particular, it has not
      been completely clarified if low T might be considered a cause or a consequence
      of MetS. The benefit of TRT in term of the reduction of CV risk needs to be
      confirmed in larger and longer studies.

PMID- 21720207
TI  - The follow-up of radioiodine-treated hyperthyroid patients: should thyroid
      function be monitored more frequently?
AB  - BACKGROUND: There is a lack of data regarding the timing and particularly the
      severity of hypothyroidism post radioiodine (RI). AIM: To investigate the timing
      and severity of hypothyroidism in RI-treated hyperthyroid patients. METHODS:
      Retrospective examination of the records of 183 RI-treated hyperthyroid patients
      (79 autoimmune hyperthyroidism, 46 toxic multinodular goiter, and 58
      hyperthyroidism of indeterminate etiology). RESULTS: One hundred and fifty-nine
      patients requiring a single dose of RI (435 MBq), 107 (67%) developed
      hypothyroidism. Hypothyroidism detected in: 16% of patients at <8 weeks, 46% at 8
      to <16 weeks, 24% at 16 to <24 weeks, 9% at 24 to <36 weeks, 3% at 36 to <52
      weeks, and 2% at >52 weeks. One hundred and eighty-three patients had follow-up
      after one or more doses of RI and 124 (68%) patients developed hypothyroidism; of
      these, 44 (36%) had TSH>50 mU/l and 34 (27%) had free T4<5 pmol/l when
      hypothyroidism was first detected. Of those patients with a delayed outpatient
      visit (no.=77) and those with an outpatient visit within the recommended target
      interval (no.=47), median TSH was 23 (0.05-152) mU/l and 32 (0.05-150) mU/l,
      respectively (p=0.75) and median free T4 was 7.1 (1.3-16.7) pmol/l and 6.6 (1.3
      15.4) pmol/l, respectively (p=0.21) at first detection of hypothyroidism.
      CONCLUSIONS: The severity of hypothyroidism when first detected during follow-up
      is of concern and suggests that closer monitoring of thyroid function is
      required, particularly during the first 6 months post- RI therapy.

PMID- 21720208
TI  - [IgG4-related disease].

PMID- 21720209
TI  - mRNA expression profiling reveals conserved and non-conserved miR-140 targets.
AB  - microRNAs are non-coding RNAs that regulate gene expression. A significant
      proportion of microRNAs is perfectly conserved across the vertebrate clade,
      including miR-140, which is specifically expressed in cartilage. Although it has
      been computationally predicted that a large majority of microRNA targets are
      conserved, experimental evidence for this hypothesis remains scarce. In this work
      we use mRNA expression profiles obtained after manipulation of miR-140 activity
      levels in human and chicken primary chondrocytes to explore the extent of miR-140
      target conservation. Our data suggest that miR-140 has a large number of targets
      conserved between human and chicken and we validate one of these, BMP2. However,
      we also found a significant number of non-conserved targets in the two species.
      In addition, we found that a commercially available scrambled siRNA, which is
      regularly used as a negative control, regulate the accumulation of many genes.

PMID- 21720210
TI  - Proteins secreted by root-knot nematodes accumulate in the extracellular
      compartment during root infection.
AB  - Root-knot nematodes are biotrophic parasites that invade the root apex of host
      plants and migrate towards the vascular cylinder where they induce the
      differentiation of root cells into hypertrophied multinucleated giant cells.
      Giant cells are part of the permanent feeding site required for nematode
      development into the adult stage. To date, a repertoire of candidate effectors
      potentially secreted by the nematode into the plant tissues to promote infection
      has been identified. However, the precise role of these candidate effectors
      during root invasion or during giant cell induction and maintenance remains
      largely unknown. Primarily, the identification of the destination of nematode
      effectors within plant cell compartment(s) is crucial to decipher their actual
      functions. We analysed the fine localization in root tissues of five nematode
      effectors throughout the migratory and sedentary phases of parasitism using an
      adapted immunocytochemical method that preserves host and pathogen tissues.  We
      showed that secretion of effectors from the amphids or the oesophageal glands is
      tightly regulated during the course of infection. The analysed effectors
      accumulated in the root tissues along the nematode migratory path and along the
      cell wall of giant cells, showing the apoplasm as an important destination
      compartment for these effectors during migration and feeding cell formation.

PMID- 21720211
TI  - Potential role of Arabidopsis PHP as an accessory subunit of the PAF1
      transcriptional cofactor.
AB  - Paf1C is a transcriptional cofactor that has been implicated in various
      transcription-associated mechanisms spanning initiation, elongation and RNA
      processing, and is important for multiple aspects of development in Arabidopsis.
      Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of
      genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as
      an accessory subunit of Paf1C that promotes this function.

PMID- 21720212
TI  - Mannitol in six autotrophic stramenopiles and Micromonas.
AB  - Mannitol plays a central role in brown algal physiology since it represents an
      important pathway used to store photoassimilate. Several specific enzymes are
      directly involved in the synthesis and recycling of mannitol, altogether forming
      the mannitol cycle. The recent analysis of algal genomes has allowed tracing back
      the origin of this cycle in brown seaweeds to a horizontal gene transfer from
      bacteria, and furthermore suggested a subsequent transfer to the green microalga
      Micromonas. Interestingly, genes of the mannitol cycle were not found in any of
      the currently sequenced diatoms, but were recently discovered in pelagophytes and
      dictyochophytes. In this study, we quantified the mannitol content in a number of
      ochrophytes (autotrophic stramenopiles) from different classes, as well as in
      Micromonas. Our results show that, in accordance with recent observations from
      EST libraries and genome analyses, this polyol is produced by most ochrophytes,
      as well as the green alga tested, although it was found at a wide range of
      concentrations. Thus, the mannitol cycle was probably acquired by a common
      ancestor of most ochrophytes, possibly after the separation from diatoms, and may
      play different physiological roles in different classes.

PMID- 21720213
TI  - Human colon cancer stem cells are enriched by insulin-like growth factor-1 and
      are sensitive to figitumumab.
AB  - Cancer stem cells (CSCs) are recognized as contributors to cancer progression and
      therapeutic resistance in liquid and solid malignancies. We analyzed a panel of
      human colon cancer cell lines for CSC populations by side population and aldehyde
      dehydrogenase activity. IGF-1 enriches these putative colon CSC populations in a
      beta-catenin-dependent manner. Chemical inhibition of Akt depletes SP cells, and
      conversely, the overexpression of a constitutively active mutant version of Akt
      is sufficient to enrich CSC populations. CP-751,871, a fully human antibody with
      specificity to the IGF-1 receptor, is currently being tested in clinical trials
      for a variety of solid tumors. CP-751,871 reduces CSC populations in colon cancer
      cell lines in vitro and reduces tumor growth in vivo. We have identified a novel
      role for IGF-1 in the enrichment of chemo-resistant CSC populations. Our results
      suggest that CP-751,871 has preferential activity against putative CSC
      populations and, therefore, may complement current standard chemotherapeutic
      regimens that target cycling cells.

PMID- 21720215
TI  - From growing to secreting: new roles for mTOR in aging cells.
AB  - Deregulation of the nutrient sensitive mTOR signaling pathway has been recently
      involved in several age-related diseases, and pharmacological blockade of mTOR
      extends longevity in model organisms and in mice. Mechanistic studies in vitro
      have shed light on the role of mTOR-dependent growth signals in promoting
      senescence and exhaustion of quiescent stem cells, thus linking excess nutrients
      to tissue ageing. Novel findings add complexity to this theoretical framework,
      revealing that mTOR cooperates with autophagy to promote the "secretory
      phenotype" of senescent cells and the release of factors known to contribute to
      defective renewal and dysfunction of aging tissues. Thus, both cell autonomous
      and cell non-autonomous mechanisms link unchecked mTOR activity to cell
      senescence and by extension to the aging process.

PMID- 21720214
TI  - Gene expression signature of c-MYC-immortalized human fibroblasts reveals loss of
      growth inhibitory response to TGFbeta.
AB  - Cancer cells exhibit the ability to proliferate indefinitely, but paradoxically,
      overexpression of cellular oncogenes in primary cells can result in a rapid and
      irreversible cell cycle arrest known as oncogene-induced senescence (OIS).
      However, we have shown that constitutive overexpression of the oncogene c-MYC in
      primary human foreskin fibroblasts results in a population of cells with
      unlimited lifespan; these immortalized cells are henceforth referred to as iMYC.
      Here, in order to further elucidate the mechanisms underlying the immortalization
      process, a gene expression signature of three independently established iMYC cell
      lines compared to matched early passage c-MYC overexpressing cells was derived.
      Network analysis of this "iMYC signature" indicated that a large fraction of the
      down-regulated genes were functionally connected and major nodes centered around
      the TGFbeta, IL-6 and IGF-1 signaling pathways. Here, we focused on the
      functional validation of the alteration of TGFbeta response during c-MYC-mediated
      immortalization. The results demonstrate loss of sensitivity of iMYC cells to
      activation of TGFbeta signaling upon ligand addition. Furthermore, we show that
      aberrant regulation of the p27 tumor suppressor protein in iMYC cells is a key
      event that contributes to loss of response to TGFbeta. These findings highlight
      the potential to reveal key pathways contributing to the self-renewal of cancer
      cells through functional mining of the unique gene expression signature of cells
      immortalized by c-MYC.

PMID- 21720217
TI  - An introduction to tree-structured modeling with application to quality of life
      data.
AB  - BACKGROUND: Investigators addressing nursing research are faced increasingly with
      the need to analyze data that involve variables of mixed types and are
      characterized by complex nonlinearity and interactions. Tree-based methods, also
      called recursive partitioning, are gaining popularity in various fields. In
      addition to efficiency and flexibility in handling multifaceted data, tree-based
      methods offer ease of interpretation. OBJECTIVES: The aims of this study were to
      introduce tree-based methods, discuss their advantages and pitfalls in
      application, and describe their potential use in nursing research. METHOD: In
      this article, (a) an introduction to tree-structured methods is presented, (b)
      the technique is illustrated via quality of life (QOL) data collected in the
      Breast Cancer Education Intervention study, and (c) implications for their
      potential use in nursing research are discussed. DISCUSSION: As illustrated by
      the QOL analysis example, tree methods generate interesting and easily understood
      findings that cannot be uncovered via traditional linear regression analysis. The
      expanding breadth and complexity of nursing research may entail the use of new
      tools to improve efficiency and gain new insights. In certain situations, tree
      based methods offer an attractive approach that help address such needs.

PMID- 21720219
TI  - Allergic drug reactions: from basic research to clinical practice.

PMID- 21720220
TI  - Updates on the use of inhaled corticosteroids in asthma.
AB  - PURPOSE OF REVIEW: The purpose of this review is to compare and contrast the
      newer inhaled corticosteroid (ICS) ciclesonide with older ICSs in terms of
      pharmacodynamic and pharmacokinetic properties and how these affect comparative
      efficacy. In addition, clinical dosing strategies for ICSs including as-needed
      use will be explored. RECENT FINDINGS: Ciclesonide has demonstrated similar
      efficacy to that of fluticasone propionate and mometasone furoate in equipotent
      doses with a potentially improved therapeutic index. Once-daily administration of
      ICSs is generally not as effective as twice-daily. Continuous administration of
      ICSs does not change the natural history of asthma in either children or adults.
      Long-term administration of medium dose ICSs does not increase the risk of
      cataracts or osteopenia in children and young adults. Studies of as-needed ICSs
      in mild persistent asthma in adults and children have demonstrated mixed results,
      with some showing equal efficacy to continuous therapy and others showing
      superiority of continuous therapy. SUMMARY: Ciclesonide provides a newer ICS with
      favorable pharmacokinetics that may improve the therapeutic index, but assessment
      of its systemic effects such as growth await further studies. Continuous
      administration of ICSs in low to medium dose over many years is well tolerated.
      The use of as-needed ICSs in patients with mild persistent asthma is promising as
      a potential step-down therapy but awaits further studies.

PMID- 21720221
TI  - Current world literature.

PMID- 21720222
TI  - The diagnosis of cryptogenic stroke: is the combined ultrasound approach the
      right choice?

PMID- 21720223
TI  - In search of the best prognostic factor in patients with congestive heart
      failure: the paradox of ejection fraction without prognostic significance and the
      role of cardiopulmonary exercise testing.

PMID- 21720224
TI  - A randomized open-label comparison of the impact of aripiprazole versus
      risperidone on sexual functioning (RAS study).

PMID- 21720225
TI  - Osmotic-controlled release oral delivery system (OROS) paliperidone-related
      pruritic rash.

PMID- 21720226
TI  - Changes in the metabolic parameters and QTc interval after switching from
      olanzapine to aripiprazole in Japanese patients with stable schizophrenia.

PMID- 21720227
TI  - Adding aripiprazole to clozapine worsened delusions and hallucinations: a case
      report.

PMID- 21720228
TI  - Aripiprazole and pregnancy: a case report and literature review.

PMID- 21720229
TI  - A retrospective study exploring the effects of intramuscular aripiprazole on QTc
      change in agitated medically ill patients.

PMID- 21720230
TI  - Suicidal ideation associated with asenapine use: a report of 2 cases.

PMID- 21720231
TI  - Tardive dyskinesia related to quetiapine and confirmed by a DAT scan.

PMID- 21720232
TI  - A retrospective case series of bipolar patients with adjunctive carbamazepine in
      long-term lithium treatment: evaluation of the effectiveness.

PMID- 21720233
TI  - Adherence to medication in depressive patients.

PMID- 21720234
TI  - Low serum lithium associated with immoderate use of Coca-Cola Zero.

PMID- 21720235
TI  - Translocase of outer mitochondrial membrane 40 homolog (TOMM40) poly-T length
      modulates lorazepam-related cognitive toxicity in healthy APOE epsilon4-negative
      elderly.

PMID- 21720236
TI  - Weight-reducing effects of metformin are sustained over 40 weeks for psychiatric
      inpatients receiving polypharmacy.

PMID- 21720237
TI  - Trauma reactivation under the influence of propranolol decreases posttraumatic
      stress symptoms and disorder: 3 open-label trials.

PMID- 21720238
TI  - Sertindole-associated deep venous thrombosis.

PMID- 21720239
TI  - The absence of adrenal gland enlargement during septic shock predicts mortality:
      a computed tomography study of 239 patients.
AB  - BACKGROUND: : Assessment and management of septic shock associated adrenal
      function remain controversial. The aim of this study was to explore the
      prognostic value of adrenal gland volume in adults with septic shock. METHODS: :
      A short cosyntropin test and determination of adrenal volume by computed
      tomography were performed within 48 h of shock in patients with septic shock (n =
      184) and in 2 control groups: 40 ambulatory patients and 15 nonseptic critically
      ill patients. The primary endpoint was intensive care unit mortality. RESULTS: :
      At intensive care unit discharge, 59 patients with septic shock died. Adrenal
      volume was 12.5 cm [95% CI, 11.3-13.3] and 8 cm [95% CI, 6.8-10.1] in the
      nonseptic group (P < 0.05 with both septic cohorts) and 7.2 cm [95%CI, 6.3-8.5]
      in the ambulatory patient group (P < 0.05 in patients with septic shock). In
      patients with septic shock, adrenal volume less than 10 cm was associated with
      higher 28-day mortality rates with an area under the receiver operating curve of
      0.84 [95% CI, 0.78-0.89]. Adrenal volume above 10 cm was an independent predictor
      of intensive care unit survival (hazard ratio = 0.014; 95% CI [0.004-0.335]).
      CONCLUSION: : A total adrenal gland volume less than 10 cm during septic shock
      was associated in univariate and multivariate analysis with mortality at day 28
      in patients with septic shock. Whether adrenal gland volume can be a surrogate of
      adrenal gland function and used to guide hydrocortisone therapy in septic shock
      patients needs to be further investigated.

PMID- 21720240
TI  - Case scenario: metastatic pediatric paraganglioma presenting during the course of
      an elective surgery.

PMID- 21720241
TI  - Neural correlates of chronic low back pain measured by arterial spin labeling.
AB  - BACKGROUND: The varying nature of chronic pain (CP) is difficult to correlate to
      neural activity using typical functional magnetic resonance imaging methods.
      Arterial spin labeling is a perfusion-based imaging technique allowing the
      absolute quantification of regional cerebral blood flow, which is a surrogate
      measure of neuronal activity. METHODS: Subjects with chronic low back and
      radicular pain and matched healthy normal subjects, undergoing identical
      procedures, participated in three sessions: a characterization and training
      session and two arterial spin labeling sessions. In the first imaging session, CP
      (if any) was exacerbated using clinical maneuvers; in the second session, noxious
      heat was applied to the affected leg dermatome, the intensity of which was
      matched to the pain intensity level of the CP exacerbations for each back pain
      subject. RESULTS: The clinically significant worsening of ongoing CP (<= 30%, n =
      16) was associated with significant regional blood flow increases (6-10 mm/100 g
      of tissue/min, P less than 0.01) within brain regions known to activate with
      experimental pain (somatosensory, prefrontal, and insular cortices) and in other
      structures observed less frequently in experimental pain studies, such as the
      superior parietal lobule (part of the dorsal attention network). This effect is
      specific to changes in ongoing CP as it is observed during worsening CP, but it
      is not observed after thermal pain application, or in matched, pain-free healthy
      controls. CONCLUSIONS: Study findings demonstrate the use of arterial spin
      labeling to investigate the neural processing of CP, and these findings are a
      step forward in the quest for objective biomarkers of the chronic pain
      experience.

PMID- 21720242
TI  - Estimating anesthesia time using the medicare claim: a validation study.
AB  - INTRODUCTION: Procedure length is a fundamental variable associated with quality
      of care, though seldom studied on a large scale. The authors sought to estimate
      procedure length through information obtained in the anesthesia claim submitted
      to Medicare to validate this method for future studies. METHODS: The Obesity and
      Surgical Outcomes Study enlisted 47 hospitals located across New York, Texas, and
      Illinois to study patients undergoing hip, knee, colon, and thoracotomy
      procedures. A total of 15,914 charts were abstracted to determine body mass index
      and initial patient physiology. Included in this abstraction were induction, cut,
      close, and recovery room times. This chart information was merged to Medicare
      claims that included anesthesia Part B billing information. Correlations between
      chart times and claim times were analyzed, models developed, and median absolute
      differences in minutes calculated. RESULTS: Of the 15,914 eligible patients,
      there were 14,369 for whom both chart and claim times were available for
      analysis. For these 14,369, the Spearman correlation between chart and claim time
      was 0.94 (95% CI 0.94, 0.95), and the median absolute difference between chart
      and claim time was only 5 min (95% CI: 5.0, 5.5). The anesthesia claim can also
      be used to estimate surgical procedure length, with only a modest increase in
      error. CONCLUSION: The anesthesia bill found in Medicare claims provides an
      excellent source of information for studying surgery time on a vast scale
      throughout the United States. However, errors in both chart abstraction and
      anesthesia claims can occur. Care must be taken in the handling of outliers in
      these data.

PMID- 21720243
TI  - Use of recombinant factor VIIa in patients with amniotic fluid embolism: a
      systematic review of case reports.
AB  - BACKGROUND: Patients with amniotic fluid embolism (AFE) (major cardiac and
      pulmonary symptoms plus consumptive coagulopathy) have high circulating tissue
      factor concentrations. Recombinant factor VIIa (rVIIa) has been used to treat
      hemorrhage in AFE patients even though rVIIa can combine with circulating tissue
      factor and form intravascular clots. A systematic review was done of case reports
      from 2003 to 2009 of AFE patients with massive hemorrhage who were and were not
      treated with rVIIa to assess the thrombotic complication risk. METHODS: MEDLINE
      was searched for case reports of AFE patients receiving rVIIa (rVIIa cases) and
      of AFE patients who received surgery to control bleeding but no rVIIa (cohorts
      who did not receive rVIIa). Additional AFE case reports were obtained from the
      Food and Drug Administration, the Australian and New Zealand Haemostasis
      Registry, and scientific meeting abstracts. The risk of a negative outcome
      (permanent disability or death) in rVIIa cases versus cohorts who did not receive
      rVIIa was calculated using risk ratio and 95% confidence interval. RESULTS:
      Sixteen rVIIa cases and 28 cohorts were identified who did not receive rVIIa. All
      patients had surgery to control bleeding. Death, permanent disability, and full
      recovery occurred in 8, 6, and 2 rVIIa cases and 7, 4, and 17 cohorts who did not
      receive rVIIa (risk ratio 2.2, 95% CI 1.4-3.7 for death or permanent disability
      vs. full recovery). CONCLUSION: Recombinant factor VIIa cases had significantly
      worse outcomes than cohorts who did not receive rVIIa. It is recommended that
      rVIIa be used in AFE patients only when the hemorrhage cannot be stopped by
      massive blood component replacement.

PMID- 21720244
TI  - Recent advances in biomarkers in osteoarthritis.
AB  - PURPOSE OF REVIEW: Osteoarthritis is a joint disease characterized by a
      nonsymptomatic, preradiographical phase that if distinguished would allow earlier
      osteoarthritis diagnosis. Biochemical biomarkers offer a potential
      nonradiographical alternative to detect early, nonsymptomatic osteoarthritis.
      RECENT FINDINGS: Biomarker development for osteoarthritis diagnosis is still in
      the forefront of the research repertoire in osteoarthritis. A number of
      previously identified biomarkers derived from cartilage breakdown or enzymes that
      cause cartilage degeneration still have prominence and are now better
      characterized with increasing use in identifying disease severity, progression,
      and testing treatment options. Combinations of cartilage-derived and bone-derived
      biomarkers have been used to subgroup osteoarthritis patients that could impact
      treatment and address the importance of bone turnover in cartilage integrity.
      Increasingly, inflammation markers have been used to profile osteoarthritis
      progression attesting to the inflammatory nature of osteoarthritis. The
      application of proteomic technologies has generated several new, nonconventional
      biomarkers that could allow better profiling of osteoarthritis. SUMMARY:
      Biomarker combinations have the ability to subgroup the heterogenous
      osteoarthritis population to allow a better scrutiny of diagnosis and treatment
      options. The application of different technological platforms to osteoarthritis
      would allow a better understanding of its pathology and could provide for
      appropriate candidates for earlier detection of osteoarthritis.

PMID- 21720245
TI  - Effector T-cell subsets in systemic lupus erythematosus: update focusing on Th17
      cells.
AB  - PURPOSE OF REVIEW: The discovery of T helper (Th)17 cells that produce the
      proinflammatory cytokine IL-17 has substantially advanced our understanding of T
      cell biology and autoimmunity. We will review recent findings on effector T
      cells, in particular Th17 cells, in lupus. RECENT FINDINGS: Studies reported
      increased IL-17 levels in the circulation and tissues in human and murine lupus.
      Patients with systemic lupus erythematosus (SLE or lupus) had an increased
      frequency of Th17 cells in peripheral blood which correlated with disease
      activity. However, the frequency of IFN-gamma-producing Th1 cells did not change
      in the same patients, suggesting a selective dysregulation of Th17 cells in SLE.
      In addition, patients with SLE had an increased frequency of IL-17-producing
      CD3CD4CD8 (double negative) T cells in the peripheral blood and kidneys. Similar
      findings were noticed in lupus-prone MRL/MP-lpr/lpr (MRL/lpr) mice. A recent
      study demonstrated that IL-17 could promote B-cell survival and differentiation
      into antibody-producing cells. This raises the possibility that IL-17 is
      implicated in the pathogenesis of SLE by promoting humoral immunity against self
      antigen. SUMMARY: Emerging data show a body of evidence that IL-17 and Th17 cells
      may play a role in the pathogenesis of SLE. Further studies are warranted to
      dissect the mechanism for increased IL-17 production and the therapeutic
      implication of targeting this cytokine in SLE.

PMID- 21720246
TI  - Targeting lymphocyte signaling pathways as a therapeutic approach to systemic
      lupus erythematosus.
AB  - PURPOSE OF REVIEW: Over the past year several key pathways in systemic lupus
      erythematosus (SLE) lymphocyte signaling have been identified. Pathways that can
      be exploited for therapy are discussed in this review. RECENT FINDINGS:
      Inhibition of SLE T cell activation by blocking spleen tyrosine kinase (Syk) and
      SLE T cell migration by blocking CD44 or CXCR4 lead to amelioration of lupus in
      lupus-prone mice. Similar results can be achieved by boosting CD8+ Treg numbers.
      Small molecules that block the kinases CaMKIV (calcium and calmodulin dependent
      kinase IV) and Bruton Tyrosine kinase (Btk) and the phosphatase calcineurin were
      shown to be effective in treating murine lupus. Finally, gene methylation status
      determines the expression of several key genes in SLE and strategies to correct
      it have shown promising results in preclinical studies. SUMMARY: Molecules that
      enhance T cell receptor (TCR) signaling or increase lymphocyte migration can be
      inhibited successfully with significant improvement of disease intensity in lupus
      prone mice using small molecules. Manipulation of promoter methylation and
      histone acetylation represents a novel way to alter gene transcription in SLE.

PMID- 21720247
TI  - Mycophenolate mofetil in the treatment of systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: Clinicians are increasingly using mycophenolate mofetil (MMF)
      for the treatment of systemic lupus erythematosus (SLE). This review will discuss
      the key studies that have contributed to our understanding of the efficacy and
      safety of MMF in the treatment of SLE. RECENT FINDINGS: The Aspreva Lupus
      Management Study (ALMS) firmly established that MMF is equivalent to intravenous
      pulse cyclophosphamide (IVC) for the induction treatment of lupus nephritis. In
      addition, MMF was shown to be superior to azathioprine in decreasing the
      incidence of treatment failure during maintenance therapy. A posthoc analysis of
      the induction phase of ALMS suggested that MMF also improved nonrenal
      manifestations of SLE. In contrast to the ALMS maintenance results, a European
      trial concluded that MMF and azathioprine were equivalent in the ability to
      prevent renal flare after induction treatment with low-dose IVC. SUMMARY:
      Favorable efficacy and safety results of several clinical trials conducted over
      the past 10 years have led to the adoption of MMF for the treatment of lupus
      nephritis and nonrenal lupus. Future research will be important to more fully
      understand the best dosing regimen of MMF for induction versus maintenance
      treatment, total duration of treatment, and the utility of therapeutic monitoring
      of MMF levels.

PMID- 21720248
TI  - Is hospital patient safety a good candidate for resource dependence and
      transaction costs explanations?

PMID- 21720249
TI  - Innovative culture in long-term care settings: the influence of organizational
      characteristics.
AB  - BACKGROUND: Innovative cultures have been reported to enhance the creation and
      implementation of new ideas and working methods in organizations. Although there
      is considerable research on the impact of organizational context on the
      innovativeness of organizations, the same is not the case for research on the
      organizational characteristics responsible for an innovative culture in (long
      term) care settings. PURPOSE: The aim of this study was to identify
      organizational characteristics that explain innovative culture in the (long-term)
      care sector. METHODOLOGY: A large cross-sectional study in Dutch long-term care
      nursing homes and/or elderly homes, care organizations for the handicapped, and
      long-term mental health care organizations-was conducted. A total of 432 managers
      and care professionals in 37 organizations participated. The Group Innovation
      Inventory was used to measure innovative culture in long-term care organizations.
      Structural characteristics of the organization were centralization and
      formalization, environmental dynamism and competitiveness, internal and external
      exchange of information, leadership style, commitment to quality improvement, and
      the organization's innovative strategy. FINDINGS: The determinants of an
      innovative culture were estimated with a two-level random-intercepts and fixed
      slopes model. Multilevel regression models were used to account for the
      organizational clustering of individuals within the 37 care organizations.
      Environmental dynamism, job codification, formal external exchange of
      information, transformational leadership, commitment to quality, and an
      exploratory and exploitative innovation strategy were all significantly
      correlated with an innovative culture in the multivariate multilevel analysis;
      the other characteristics were not. The explained organizational- and individual
      level variance was 52.5% and 49.2%, respectively. PRACTICE IMPLICATIONS: The
      results point to substantial differences in innovative cultures between and
      within care organizations that can, in part, be explained by organizational
      characteristics. Efforts must be made to ensure that organizational
      characteristics such as environmental dynamism do not hamper the development of
      innovative cultures in long-term care organizations. Organizations' human
      resource practices and knowledge management are particularly promising in
      strengthening innovative cultures.

PMID- 21720250
TI  - Utility of tumor marker HE4 to predict depth of myometrial invasion in
      endometrioid adenocarcinoma of the uterus.
AB  - OBJECTIVE: The purpose of this pilot study was to determine whether the biomarker
      human epididymis protein 4 (HE4) correlates with depth of myometrial invasion,
      histologic grade, lymph vascular space invasion, positive cytologic washings, and
      nodal metastases in patients with endometrioid adenocarcinoma of the uterus.
      METHODS: This was a prospective, observational study in women with biopsy-proven
      endometrioid adenocarcinoma. Concentrations of HE4 were assessed before surgery,
      and all surgical specimens were reviewed by dedicated gynecologic pathologists.
      RESULTS: Included were a total of 96 women with endometrioid adenocarcinomas of
      the uterus, most (77%) with stage I disease. Levels of serum HE4 greater than 70
      pM displayed a sensitivity of 94% and a negative predictive value of 97% in
      identifying stage IA (<50% myometrial invasion) versus stage IB (>= 50%
      myometrial invasion) tumors and a sensitivity of 82% and negative predictive
      value of 82% versus all more advanced tumors. CONCLUSIONS: Human epididymis
      protein 4 may be a useful marker preoperatively in the clinical decision process
      for determining the need for lymph node dissection in women with endometrioid
      endometrial cancer.

PMID- 21720251
TI  - The relationship between ERCC1 expression and clinical outcome in patients with
      FIGO stage I to stage II uterine cervical adenocarcinoma.
AB  - OBJECTIVE: Several studies have suggested that excision repair cross
      complementation group 1 (ERCC1), a protein involved in nucleotide excision
      repair, is associated with resistance to platinum agent-based chemotherapy or
      chemoradiotherapy with platinum agents in various types of cancer. Herein we
      evaluated ERCC1 protein expression in uterine cervical adenocarcinoma and the
      relationship between this expression, clinicopathological factors, and clinical
      outcome, particularly in patients receiving adjuvant cisplatin-based chemotherapy
      or chemoradiotherapy with cisplatin. METHODS: Thirty-six patients with
      International Federation of Gynecology and Obstetrics (FIGO) stage IB to stage
      IIB cervical adenocarcinoma who underwent radical hysterectomy were evaluated.
      Excision repair cross-complementation group 1 protein expression was examined by
      immunohistochemistry in tumor tissues. The relationship between ERCC1 expression
      levels and clinicopathological factors (age, FIGO stage, histological grade,
      tumor size, vascular invasion, cervical stromal invasion, and lymph node
      metastases) and prognosis was evaluated. RESULTS: No significant differences
      between ERCC1 expression levels and clinicopathological factors were observed.
      The patients in the ERCC1 high-expression group (n = 7) experienced significantly
      worse disease-free survival than the patients in the ERCC1 low-expression group
      (n = 29; P = 0.005). Among the 25 patients who received cisplatin-based
      chemotherapy or chemoradiotherapy with cisplatin, those with high ERCC1
      expression (n = 5) also experienced significantly worse disease-free survival
      than those with low ERCC1 expression (n = 20; P = 0.002). Moreover, univariate
      and multivariate analyses revealed that high ERCC1 expression was an independent
      prognostic factor in patients receiving cisplatin-based chemotherapy or
      chemoradiotherapy with cisplatin. CONCLUSIONS: This is the first analysis of the
      association between ERCC1 expression and clinical outcomes in patients with
      uterine cervical adenocarcinoma. High ERCC1 protein expression was revealed to be
      associated with worse disease-free survival in the patients who received adjuvant
      cisplatin-based chemotherapy or chemoradiotherapy with cisplatin and was shown to
      be an independent prognostic factor. Further evaluation with a larger number of
      patients is required to confirm these preliminary observations.

PMID- 21720252
TI  - Stage III uterine carcinosarcoma: 2009 International Federation of Gynecology and
      Obstetrics Staging System and Prognostic Determinants.
AB  - OBJECTIVES: (1) To determine the significance of positive peritoneal cytology and
      pelvic versus para-aortic lymph node involvement in uterine carcinosarcoma. (2)
      To evaluate the impact of isolated retroperitoneal lymph node involvement (IIIC
      N) versus retroperitoneal lymph node involvement plus other evidence of
      extrauterine disease spread (IIIC-N+) on survival in patients with stage IIIC
      uterine carcinosarcoma. METHODS: Data were extracted from the Surveillance,
      Epidemiology, and End Results database between 1988 and 2005. Statistical
      analysis used chi, Kaplan-Meier method, and Cox proportional hazards model.
      RESULTS: A total of 690 women were identified. When comparing overall survival
      between patients with disease spread to uterine serosa and/or adnexa and those
      with positive peritoneal cytology, there was no significant difference (25.4% vs
      15.5%, P = 0.2). However, although the 5-year overall survival was comparable
      between patients with positive pelvic lymph nodes and those with positive para
      aortic lymph nodes (22.1% vs 25.4%, P = 1.0), it was significantly worse in stage
      IIIC-N(+) compared to stage IIIC-N patients (15.0% vs 33.4%, P < 0.001). Only
      patient's age (P < 0.001), race (P = 0.03), stage (P < 0.03), and lymphadenectomy
      (P < 0.001) were independent predictors of survival after adjusting for other
      contributing factors. In addition, the results of unadjusted analysis concerning
      the survival difference between different stage groups were confirmed on
      multivariate analysis. CONCLUSIONS: Positive peritoneal cytology is associated
      with poor prognosis in uterine carcinosarcoma, comparable to current
      International Federation of Gynecology and Obstetrics stage IIIA classification
      of disease. Although there does not seem to be a significant survival difference
      between patients with positive pelvic versus those with para-aortic lymph nodes,
      the prognosis seems to be much worse in patients with stage IIIC uterine
      carcinosarcoma with other evidence of extrauterine disease spread, suggesting the
      need for more aggressive therapy.

PMID- 21720253
TI  - Crosstalk between estrogen receptor and mitogen-activated protein kinase
      signaling in the development and progression of endometrial cancer.
AB  - OBJECTIVE: The objectives of the study were to evaluate the role of mitogen
      activated protein kinase (MAPK) signaling in normal, hyperplastic, and neoplastic
      endometrium in relation to estrogen receptor (ER) status and to investigate
      whether 17beta-estradiol (E2) and tamoxifen (TAM) mediate the proliferation and
      apoptosis of endometrial cancer cells through the MAPK pathway. METHODS: The
      expressions of phosphorylated and total extracellular signal-regulated kinases
      1/2 (phosphorylated extracellular signal-regulated kinase 1/2 [p-ERK1/2] and
      total ERK1/2 [t-ERK1/2]) were analyzed with immunohistochemistry in normal,
      hyperplastic, and neoplastic endometrium. The expression levels of p-ERK1/2 and t
      ERK1/2 in RL95-2 and KLE after stimulation by E2, progesterone (P), and TAM were
      detected by Western blotting. The effects of E2 and TAM in combination with MAPK
      pathway inhibitors on the growth and apoptosis of endometrial cancer cells were
      examined by the MTS assay and flow cytometry analysis. RESULTS: The expression
      level of p-ERK1/2 was significantly associated with the International Federation
      of Gynecology and Obstetrics stage (P = 0.0072). The ratio of
      phosphorylated/total ERK1/2 was higher in ER-positive endometrial cancer tissues
      and cells (P < 0.05). 17beta-Estradiol increased ERK1/2 phosphorylation, and TAM
      decreased ERK1/2 phosphorylation in endometrial cancer cell lines within 30
      minutes (P < 0.05). The MEK1/2 inhibitor, U0126, and the stress-activated protein
      kinase/c-Jun NH2-terminal kinase inhibitor, SP600125, significantly suppressed
      the proliferation of human endometrial cancer cell lines RL95-2 and KLE induced
      by E2 (P < 0.05). The level of TAM-induced apoptosis was greater in KLE than in
      RL95-2 cells, and the p38 cascade was involved in the TAM-induced apoptosis of
      both cell lines (P < 0.05). CONCLUSIONS: The cross-talk between MAPK signaling
      and ER status might exert a key role in progression of endometrial cancer.
      Furthermore, the effects of E2 or TAM on the proliferation or apoptosis of ER
      positive and ER-negative endometrial cancer cells were mediated through distinct
      MAPK pathways. These mechanisms might contribute to ER-specific differences in
      MAPK activation for molecular-target therapies in endometrial carcinoma.

PMID- 21720254
TI  - A single-institution evaluation of factors important in fallopian tube carcinoma
      recurrence and survival.
AB  - OBJECTIVE: The aim of this study was to identify prognostic factors and markers
      that influence clinical outcomes in patients with primary fallopian tube
      carcinoma at a single tertiary health care center. These prognostic factors may
      be of clinical importance and can subsequently be included in future clinical
      trials. MATERIALS AND METHODS: A retrospective review of our Tumor Registry and
      Gynecologic Oncology database was conducted to include any patients with a
      diagnosis of fallopian tube carcinoma between the years 1994 and 2005. We
      identified clinicopathological data to evaluate factors important in recurrence,
      disease-specific and overall survival. Kaplan-Meier curves were generated, and
      log-rank tests were used to evaluate survival differences. RESULTS: Thirty-six
      patients had a diagnosis with primary fallopian tube carcinoma at a median age of
      69 years. Patients most frequently presented with abdominal pain (19%) and a
      palpable mass (14%). The most common histological subtype was papillary serous
      adenocarcinoma in 56% of cases. Stage III disease (39%) and poorly differentiated
      tumors (81%) were most common. The median follow-up was 39.6 months. The 5-year
      cancer-specific survival was 42%, and the overall survival rate was 34%. Factors
      important in disease-free survival were International Federation of Gynecology
      and Obstetrics stage, tumor laterality, and serum CA-125, whereas International
      Federation of Gynecology and Obstetrics stage, serum CA-125, and residual disease
      were prognostic factors for overall survival. The most common locations of
      recurrence were pelvis and abdomen (63%) as opposed to distant sites. Factors
      associated with recurrence were stage, tumor laterality, and serum CA-125.
      CONCLUSIONS: Fallopian tube malignancies are rare. We have identified factors
      associated with recurrence, disease specific survival, and overall survival that
      could be further examined and included in larger clinical trials involving this
      uncommon malignancy.

PMID- 21720255
TI  - Training in bowel and upper abdominal surgery in gynaecological oncology:
      European Society of Gynecological Oncology (ESGO) Statement.

PMID- 21720256
TI  - Gynecologic oncology training systems in Europe: a report from the European
      network of young gynaecological oncologists.
AB  - OBJECTIVE: The objectives of the study were to highlight some of the differences
      in training systems and opportunities for training in gynecologic oncology across
      Europe and to draw attention to steps that can be taken to improve training
      prospects and experiences of European trainees in gynecologic oncology. METHODS:
      The European Network of Young Gynaecological Oncologists national representatives
      from 34 countries were asked to review and summarize the training system in their
      countries of origin and fulfill a mini-questionnaire evaluating different aspects
      of training. We report analysis of outcomes of the mini-questionnaire and
      subsequent discussion at the European Network of Young Gynaecological Oncologists
      national representatives Asian Pacific Organization for Cancer Prevention meeting
      in Istanbul (April 2010). RESULTS: Training fellowships in gynecologic oncology
      are offered by 18 countries (53%). The median duration of training is 2.5 years
      (interquartile range, 2.0-3.0 years). Chemotherapy administration is part of
      training in 70.5% (24/34) countries. Most of the countries (26/34) do not have a
      dedicated national gynecologic-oncology journal. All trainees reported some or
      good access to training in advanced laparoscopic surgical techniques, whereas 41%
      indicated no access, and 59% some access to training opportunities in robotic
      surgery. European countries were grouped into 3 different categories on the basis
      of available training opportunities in gynecologic oncology: well-structured,
      moderately structured, and loosely structured training systems. CONCLUSIONS:
      There is a need for further harmonization and standardization of training
      programs and structures in gynecologic oncology across Europe. This is of
      particular relevance for loosely structured countries that lag behind the
      moderately structured and well-structured ones.

PMID- 21720257
TI  - Serum tryptophan and kynurenine concentrations as parameters for indoleamine 2,3
      dioxygenase activity in patients with endometrial, ovarian, and vulvar cancer.
AB  - OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) suppresses the function of T
      lymphocytes and is involved in immune escape of cancers. Indoleamine 2,3
      dioxygenase catalyzes the initial rate-limiting step in the degradation of the
      essential amino acid tryptophan. In this study, we investigated cancer-induced
      IDO activity in sera of endometrial, ovarian, and vulvar cancer patients.
      METHODS: Concentrations of tryptophan and kynurenine were determined in
      pretreatment serum samples of patients with endometrial (n = 41), ovarian (n =
      28), and vulvar cancer (n = 40) and compared to 19 healthy female controls. In
      serum of a subgroup of endometrial (n = 22), ovarian (n = 21), and vulvar (n =
      21) cancer patients, tryptophan, kynurenine, and the kynurenine-to-tryptophan
      ratio (kyn/trp) were determined at different time points: preoperative, at
      clinical remission, and at the time of diagnosis of recurrent disease. Analyses
      were performed by an automated online solid-phase extraction-liquid
      chromatographic-tandem mass spectrometric method. Indoleamine 2,3-dioxygenase
      activity was estimated by calculating the kyn/trp ratio. RESULTS: Kynurenine
      concentrations and the kyn/trp ratio were higher in preoperative serum of
      endometrial, ovarian, and vulvar cancer patients compared to controls (all: P <
      0.001). Preoperative serum of ovarian cancer patients contained higher kynurenine
      concentrations (median, 2.53 MUM; interquartile range [IQR], 1.72-4.29 MUM) and a
      higher kyn/trp ratio (median, 39.3 MUmol/mmol; IQR, 26.5-61.7 MUmol/mmol)
      compared to serum collected at clinical remission (median, 2.02 MUM; IQR, 1.68
      2.72 MUM, P = 0.035; and median, 29.9 MUmol/mmol; IQR, 23.4-38.9 MUmol/mmol, P =
      0.005, respectively). CONCLUSIONS: Patients with endometrial, ovarian, and vulvar
      cancer have increased tryptophan degradation compared to controls resulting in
      higher serum kynurenine concentrations and a higher kyn/trp ratio. Our results
      suggest that IDO-induced immune escape may play an important role in these
      gynecologic cancers.

PMID- 21720258
TI  - The role of hormonal therapy in gynecological cancers-current status and future
      directions.
AB  - Many gynecological cancers, including epithelial and stromal ovarian cancers;
      endometrial carcinomas; and some gynecological sarcomas, in particular
      endometrial stromal sarcomas, express estrogen and/ or progesterone receptors.
      Hormonal therapy, typically progestogens or tamoxifen, is commonly prescribed to
      patients with potentially hormone-sensitive recurrent or metastatic gynecological
      cancers with very variable response rates and clinical benefit reported.
      Aromatase inhibitors are now widely used to treat postmenopausal women with
      hormone receptor-positive breast cancers as they have greater activity than
      tamoxifen and are generally better tolerated. The role of aromatase inhibitors in
      gynecological cancers is uncertain and has not been well studied, although they
      do appear to be active. The current evidence to support the use of hormonal
      therapies including aromatase inhibitors in gynecological cancers is reviewed,
      and the gaps in our knowledge highlighted.

PMID- 21720259
TI  - The cues and care randomized controlled trial of a neonatal intensive care unit
      intervention: effects on maternal psychological distress and mother-infant
      interaction.
AB  - OBJECTIVE: This study tested the efficacy of a brief intervention (Cues program)
      with mothers of very low birth weight (VLBW <1500 g) infants. The primary
      hypothesis was that mothers in the Cues program would report lower levels of
      anxiety compared with mothers in the control group. Secondary hypotheses examined
      whether Cues mothers would report less stress, depression, and role restriction,
      and exhibit more sensitive interactive behavior, than control group mothers.
      METHODS: A total of 121 mothers of VLBW infants were randomly assigned to either
      the experimental (Cues) intervention or an attention control (Care) condition.
      The Cues program combined training to reduce anxiety and enhance sensitivity. The
      control group received general information about infant care. Both programs were
      initiated during the neonatal intensive care unit stay. Maternal anxiety, stress,
      depression, and demographic variables were evaluated at baseline, prior to
      randomization. Postintervention outcomes were assessed during a home visit when
      the infant was ~6 to 8 weeks of corrected age. RESULTS: Although mothers in the
      Cues group demonstrated greater knowledge of the content of the experimental
      intervention than mothers in the Care group, the groups did not differ in levels
      of anxiety, depression, and symptoms of posttraumatic stress. They were similar
      in their reports of parental role restrictions and stress related to the infant's
      appearance and behavior. Cues and Care group mothers were equally sensitive in
      interaction with their infants. CONCLUSION: Nonspecific attention was as
      effective as an early skill-based intervention in reducing maternal anxiety and
      enhancing sensitive behavior in mothers of VLBW infants.

PMID- 21720260
TI  - No effect of ultraviolet radiation on blood pressure and other cardiovascular
      risk factors.
AB  - OBJECTIVES: Recent epidemiological studies have reported inverse associations
      between vitamin D status and blood pressure. The study aim is to determine if
      exposure to ultraviolet B radiation, which synthesizes vitamin D, lowers blood
      pressure, compared with ultraviolet A radiation. METHODS: Men and women (n = 119)
      with low vitamin D levels [serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/l],
      completed a randomized clinical trial carried out during winter. Blood pressure
      was measured for 12-14 h with an ambulatory monitor at baseline and 12 weeks. In
      between, participants received 24 whole body exposures of either ultraviolet B (n
      = 58) or ultraviolet A (n = 61) over 12 weeks. RESULTS: Mean (SD) 25(OH)D
      increased from 43.7 (9.7) to 92.6 (16.9) nmol/l in the ultraviolet B arm after 12
      weeks, and from 45.4 (9.2) to 64.9 (11.3) nmol/l in the ultraviolet A arm.
      However, mean blood pressure, which was similar for the ultraviolet B and
      ultraviolet A at baseline (134.9/79.2 vs. 132.9/77.8 mmHg; P = 0.59 and 0.56,
      respectively), did not change from baseline to 12 weeks in either group. The mean
      change [95% confidence interval (CI)] in blood pressure over this period in the
      ultraviolet B group compared with the ultraviolet A group was -2.2 (-7.8, 3.3)
      mmHg for systolic (P = 0.42) and -2.7 (-6.5, 1.0) mmHg for diastolic (P = 0.15).
      CONCLUSION: Exposure to ultraviolet B did not lower blood pressure. Our results
      suggest that if vitamin D protects against cardiovascular disease, it involves
      some mechanism other than blood pressure.

PMID- 21720261
TI  - Concurrent primary aldosteronism and subclinical cortisol hypersecretion: a
      prospective study.
AB  - BACKGROUND: Primary aldosteronism is the most frequent cause of secondary
      hypertension and is responsible for an increased risk of cardiometabolic
      complications. A concomitant subtle cortisol hyperproduction could enhance
      cardiovascular risk. We prospectively estimated the occurrence of subclinical
      hypercortisolism in primary aldosteronism patients. METHODS: In a large
      population of hypertensive patients without clinical signs of hypercortisolism,
      76 consecutive patients with primary aldosteronism were investigated.
      Differential diagnosis between unilateral and bilateral aldosterone
      hypersecretion was made by computed tomography/MRI and/or adrenal venous sampling
      (AVS). Subclinical hypercortisolism was defined as failure to suppress plasma
      cortisol to less than 50 nmol/l after 1 mg-overnight dexamethasone, used as
      screening test, and at least one of two other abnormal hormonal parameters, that
      is, adrenocorticotrophin (ACTH) less than 2 pmol/l and urinary cortisol more than
      694 nmol/24 h. RESULTS: Three out of 76 patients had postdexamethasone plasma
      cortisol more than 50 nmol/l. Only one also showed low-normal ACTH and mildly
      elevated urinary cortisol. The patient had a right 4 cm adrenal mass.
      Laparoscopic adrenalectomy was followed by short-term steroid replacement to
      prevent adrenal insufficiency. In-situ hybridization showed CYP11B1 expression
      exclusively in tumoral tissue, whereas CYP11B2 was expressed only in a
      peritumoral region composed of zona glomerulosa-like cells, suggesting the co
      existence of a cortisol-producing adenoma and an aldosterone-producing
      hyperplasia in the same adrenal. The restoration of hormone abnormalities to
      normal levels was confirmed at 12 months of follow-up. CONCLUSION: Concurrent
      aldosterone and subclinical cortisol hypersecretion seems to be a rare event in
      primary aldosteronism patients; however, its detection by appropriate testing is
      important to avoid AVS misinterpretation.

PMID- 21720262
TI  - Urocortin 2 sustains haemodynamic and renal function during introduction of beta
      blockade in experimental heart failure.
AB  - OBJECTIVES: The challenge in management of acute decompensated heart failure
      (ADHF) is relieving congestion and improving symptoms while preserving renal and
      systemic perfusion at a level that can tolerate introduction of drugs such as
      beta-blockers which may have adverse effects acutely yet have proven benefit in
      the longer term. Urocortin 2 (Ucn2) is a novel peptide with therapeutic potential
      in heart failure. The present study investigated the effects of combined Ucn2 and
      beta-blockade in heart failure. METHODS: Ucn2 and metoprolol were administered
      for 3 h, separately and together, in eight sheep with pacing-induced congestive
      heart failure. RESULTS: Compared with time-matched controls, metoprolol
      significantly reduced heart rate (HR), left ventricular contractility, cardiac
      output (CO) and mean arterial pressure (MAP), together with increases in
      peripheral resistance and left atrial pressure (LAP). In contrast, Ucn2 elevated
      HR, contractility, CO and MAP, and decreased peripheral resistance and LAP.
      Combined Ucn2 + metoprolol produced intermediate haemodynamic effects closer to
      those observed with Ucn2 than with beta-blockade. All three active treatment
      regimes decreased plasma renin activity, whereas only Ucn2 and Ucn2 + metoprolol
      significantly reduced plasma aldosterone. Compared with metoprolol alone (which
      tended to reduce urine output and creatinine excretion/clearance), Ucn2 +
      metoprolol increased urine volume, sodium and creatinine excretion and clearance.
      CONCLUSION: Ucn2 coupled with beta-blockade in experimental heart failure
      improves CO and MAP, sustains HR, reduces peripheral resistance, LAP and
      aldosterone and augments renal function. These results suggest a role for Ucn2 as
      a short-term parenteral therapy in the initial stages of managing ADHF that
      improves tolerance to introduction of beta-blockers.

PMID- 21720263
TI  - Positive relationship of sleep apnea to hyperaldosteronism in an ethnically
      diverse population.
AB  - OBJECTIVE: Approximately, 50-60% of patients with sleep apnea have hypertension.
      To explore a mechanism of this relationship, we compared its prevalence in a
      hypertensive population with and without hyperaldosteronism. METHODS: Using the
      Kaiser Permanente Southern California database, hypertensive individuals who had
      plasma aldosterone and plasma renin activity measured between 1 January 2006 and
      31 December 2007 were evaluated. Hyperaldosteronism was defined as an aldosterone
      : renin ratio more than 30 and plasma aldosterone more than 20 ng/dl or an
      aldosterone : renin ratio more than 50 (ng/dl : ng/ml per h). Hypertension was
      identified by International Classification of Disease, Ninth Revision (ICD-9)
      coding and sleep apnea was defined by ICD-9 coding or procedural coding for
      dispensation of positive airway devices. RESULTS: Of 3428 hypertensive patients,
      575 (17%) had hyperaldosteronism. Sleep apnea was present in 18% (105) with
      hyperaldosteronism vs. 9% (251) without hyperaldosteronism (P < 0.001). Odds
      ratio for sleep apnea in patients with hyperaldosteronism was 1.8 (95% confidence
      interval 1.3-2.6) after controlling for other sleep apnea risk factors. No ethnic
      group was at greater risk for sleep apnea. CONCLUSION: The prevalence of sleep
      apnea in a diverse hypertensive population is increased in patients with
      hyperaldosteronism, even when controlling for other sleep apnea risk factors.

PMID- 21720264
TI  - In-treatment stroke volume predicts cardiovascular risk in hypertension.
AB  - OBJECTIVE: To evaluate whether lower stroke volume during antihypertensive
      treatment is a predictor of cardiovascular events independent of left ventricular
      geometric pattern. METHODS: The association between left ventricular stroke
      volume and combined cardiovascular death, stroke and myocardial infarction, the
      prespecified primary study endpoint, was assessed in Cox regression analysis
      using data from baseline and annual follow-up visits in 855 patients during 4.8
      years of randomized losartan-based or atenolol-based treatment in the Losartan
      Intervention For Endpoint reduction in hypertension (LIFE) echocardiography
      substudy. RESULTS: During follow-up, a total of 91 primary endpoints occurred. At
      baseline, lower left ventricular stroke volume was associated with smaller body
      size, female sex, lower left ventricular mass and stress-corrected midwall
      shortening, higher relative wall thickness and total peripheral resistance, more
      concentric left ventricular geometry and impaired diastolic relaxation (all P <
      0.01). Baseline stroke volume did not predict outcome. However, in time-varying
      multivariable Cox regression analysis, lower in-treatment left ventricular stroke
      volume indexed for height was associated with higher risk of cardiovascular
      events {hazard ratio 1.69 per 1 SD (6 ml/m) lower stroke volume [95% confidence
      interval (CI) 1.35-2.11], P < 0.001} independent of in-treatment left ventricular
      mass and concentric geometry and in a secondary model also independent of stress
      corrected midwall shortening, impaired diastolic relaxation, heart rate, new
      onset atrial fibrillation and study treatment [hazard ratio 1.46 per 1 SD (6
      ml/m) lower stroke volume (95% CI 1.13-1.88)]. CONCLUSION: Assessment of in
      treatment left ventricular stroke volume may reflect cardiac and vascular
      remodeling and impairment and, hence, adds information on cardiovascular risk in
      treated hypertensive patients beyond assessment of left ventricular structure
      alone. CLINICAL TRIAL REGISTRATION INFORMATION: NCT 00338260.

PMID- 21720265
TI  - Long-term treatment with nebivolol attenuates renal damage in Zucker diabetic
      fatty rats.
AB  - OBJECTIVE: Atenolol, a first-generation beta-blocker, effectively reduces blood
      pressure, although its use in metabolic syndrome remains controversial.
      Accordingly, this study evaluated the renal effects of nebivolol, a third
      generation beta-blocker with additional vasodilating activity, versus those of
      atenolol in an animal model of diabetic nephropathy. METHODS: Zucker diabetic
      fatty (ZDF) rats and control lean Zucker rats (LZRs) were treated for 6 months
      with either nebivolol or atenolol. Blood pressure, circulating insulin,
      triglycerides, cholesterol and glucose, as well as proteinuria and creatinine
      clearance were evaluated. Thiobarbituric acid-reactive species, reduced
      glutathione (GSH)/oxidized glutathione (GSSG) ratio, CuZn superoxide dismutase,
      catalase and glutathione peroxidase were determined as biomarkers of oxidative
      stress in kidney homogenates. Expression of transforming growth factor-beta1 (TGF
      beta1), alpha-smooth muscle actin (alpha-SMA), collagen type I and III,
      plasminogen activator inhibitor-1 (PAI-1), vascular and platelet endothelial cell
      adhesion molecule-1 (VCAM-1 and PECAM-1, respectively) were determined by
      immunohistochemistry. Fibrosis was evaluated by light microscopy. RESULTS: Both
      drugs induced a similar control of blood pressure throughout the study. Contrary
      to atenolol, nebivolol showed a beneficial impact on lipid profile, preserved
      glomerular filtration rate, reduced proteinuria and induced a positive regulation
      of structural podocyte proteins (nephrin and podocin) expression. Additionally
      nebivolol decreased oxidative stress biomarkers, induced a substantial reduction
      in the accumulation of extracellular matrix proteins, down-regulated the renal
      expression of VCAM-1, monocyte chemotactic protein-1 (MCP-1), ED1, alpha-SMA, TGF
      beta1 and PAI-1 and up-regulated the expression of PECAM-1. CONCLUSION: Our
      current finding underscores the importance of this therapy in hypertensive states
      concomitant with altered lipid and glucose metabolism.

PMID- 21720266
TI  - Inhibition of soluble epoxide hydrolase improves the impaired pressure
      natriuresis relationship and attenuates the development of hypertension and
      hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats.
AB  - OBJECTIVE: In the present study, we compared the effects of treatment with the
      novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1
      receptor antagonist losartan on blood pressure (BP), autoregulation of renal
      blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure
      natriuresis relationship in response to stepwise reduction in renal arterial
      pressure (RAP) in Cyp1a1-Ren-2 transgenic rats. METHODS: Hypertension was induced
      in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural
      xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with
      c-AUCB and losartan was started 48 h before initiating administration of the diet
      containing I3C. Rats were prepared for renal functional studies to evaluate in
      vivo renal autoregulatory efficiency when RAP was gradually decreased by an
      aortic clamp. RESULTS: I3C administration resulted in the development of severe
      hypertension which was associated with markedly lower basal RBF and GFR and
      substantially impaired autoregulatory efficiency as well as a suppression of the
      pressure-natriuresis relationship when compared with noninduced rats. Treatment
      with c-AUCB significantly decreased BP, improved autoregulatory efficiency of RBF
      and GFR and the slope of pressure-natriuresis relationship. Treatment with
      losartan completely prevented the impaired autoregulation and pressure
      natriuresis relationship as well as the development of hypertension in I3C
      induced rats. CONCLUSION: Our present findings indicate that chronic treatment
      with the sEH inhibitor c-AUCB substantially attenuates the development of
      malignant hypertension in I3C-induced rats likely via improvement of the renal
      autoregulatory efficiency and the pressure-natriuresis relationship.

PMID- 21720268
TI  - A point-score system superior to blood pressure measures alone for predicting
      incident hypertension: Tehran Lipid and Glucose Study.
AB  - OBJECTIVES: To examine whether modeling a set of readily available information
      could add to predictive performance of blood pressure measures. METHOD AND
      RESULTS: From participants of the ongoing Tehran Lipid And Glucose Study, which
      has been followed for 6 years, 4656 (2695 women) nondiabetic adults, free from
      hypertension at baseline with no history of cardiovascular disease (mean age 42
      years), were selected for the current analyses. We ascertained 805 cases of
      incident hypertension. Incident rate (per 1000 person-years) was 29.3 [95%
      confidence interval (CI) 26.7-32.1] for women and 30.9 (95% CI 27.8-34.3) for men
      (P = 0.457). In multivariable analyses, age, SBP, and DBP significantly
      contributed to the risk of incident hypertension in both sexes, waist
      circumference and family history of premature cardiovascular disease among women,
      and smoking among men. A point-score system for predicting incident hypertension
      was developed by converting Weibull regression coefficients of predictors to
      integer values and its performances were compared with those of SBP and DBP. The
      C-statistic for the prediction model was 0.730 among women and 0.741 among men,
      and calibration was good in both sexes. Relative integrated discrimination
      improvement and cut-point-free net reclassification improvement for the point
      score system vs. SBP ranged between 22.0 and 69.7%. The corresponding figures for
      DBP ranged between 29.6 and 51.3%. CONCLUSION: In this large, community-based
      study, the simplified utilization of the survival regression models was superior
      to blood pressure measures alone for predicting incident hypertension.

PMID- 21720267
TI  - Risk factor profile for chronic kidney disease is similar to risk factor profile
      for small artery disease.
AB  - BACKGROUND AND METHOD: We investigated whether chronic kidney disease detected by
      increased serum creatinine (S(Cr)) or urine albumin-to-creatinine ratio (U(ACR))
      may reflect arteriosclerosis involving the kidneys. The sample consisted of 1585
      members of sibships (804 non-Hispanic whites and 781 non-Hispanic blacks) in
      which at least two siblings had primary hypertension. We first evaluated the
      correlations of increased S(Cr) and U(ACR) with the presence of cerebral small
      vessel arteriosclerosis, which was determined by increased subcortical white
      matter hyperintensity (WMH) volume on brain magnetic resonance imaging; and with
      peripheral large vessel arteriosclerosis, which was determined by decreased ankle
      brachial index (ABI). After age adjustment, increased S(Cr) and U(ACR) correlated
      with increased WMH volume (0.54 and 0.52, respectively) and with decreased ABI
      (0.50 and 0.54, respectively; all P < 0.001). We then used logistic regression to
      evaluate the dependency of each measure of disease on conventional risk factors
      for arteriosclerosis to assess whether the risk factors' effects were
      proportional across different measures of disease. RESULTS: Age, race, sex,
      hypertension, diabetes, total cholesterol, and smoking made similar overall
      contributions to the prediction of each measure of disease, as judged by the
      model C-statistics, which varied in a narrow range from 0.84 to 0.85 (all P <
      0.001). However, the relative contributions that the modifiable risk factors,
      including hypertension, diabetes, total cholesterol, and smoking made to
      prediction of increased S(Cr) and U(ACR) were disproportionate to their relative
      contributions to prediction of decreased ABI (P < 0.0001). CONCLUSION: The
      findings support the view that chronic kidney disease detected by increased S(Cr)
      or U(ACR) primarily reflects small vessel arteriosclerosis involving the kidneys.

PMID- 21720269
TI  - High blood pressure and obesity: disparities among four French Overseas
      Territories.
AB  - BACKGROUND AND PURPOSE: The epidemiological characteristics of hypertension and
      obesity in French Overseas Territories (FOTs) have never been compared. METHODS:
      This cross-sectional survey included representative population-based samples of
      602, 601, 620 and 605 men and women aged more than 15 years, respectively, from
      four FOTs of Guadeloupe, Martinique, French Guiana, and French Polynesia.
      Hypertension was defined as blood pressure (BP) at least 140/90 mmHg or the
      current use of antihypertensive treatment. RESULTS: The prevalence of
      hypertension was 29.2% in Guadeloupe, 17.9% in French Guiana, 27.6% in Martinique
      and 24.5% in French Polynesia. Considering the Guadeloupe population as the
      reference group, prevalence of hypertension was significantly lower in French
      Guiana (P < 0.001), even after controlling for age and sex (P = 0.006). Awareness
      and treatment of hypertension were similar in French Guiana, Martinique and
      Guadeloupe (68.8-75.1% and 69.0-73.4%, respectively). Awareness was lower in
      French Polynesia (50.0%, adjusted P value = 0.04), as was treatment of
      hypertension (32.4%, adjusted P value = 0.001). Control of hypertension was also
      lower in French Polynesia (8.8%, adjusted P value = 0.001) compared with the
      other territories (29.7-31.8%). French Polynesia had the highest prevalence of
      obesity (33.1%, adjusted P value < 0.001) as compared with the other territories
      (17.9-22.8%). It had also the largest population attributable fraction of
      hypertension due to obesity (35.5%) compared with Guadeloupe (13.3%), Martinique
      (12.3%) and French Guiana (23.6%). CONCLUSION: Wide variations were observed in
      the prevalence and the management of hypertension between these FOTs, and an
      especially challenging low control of hypertension was found in French Polynesia.
      Obesity appears a key target to prevent hypertension, particularly in French
      Polynesia.

PMID- 21720271
TI  - Insulin promotes vascular smooth muscle cell proliferation via microRNA-208
      mediated downregulation of p21.
AB  - OBJECTIVE: Abnormal vascular smooth muscle cell (VSMC) proliferation is involved
      in the development of vascular diseases. However, the mechanisms by which insulin
      exerts this effect are not completely known. We hypothesize that microRNAs might
      be involved in insulin-induced VSMC proliferation. METHODS: VSMC proliferation
      was determined by [H]-thymidine incorporation; microRNAs were determined by
      microRNA chips and real-time PCR; and p21expression was determined by
      immunoblotting. RESULTS: In this study, we found that insulin increased VSMC
      proliferation and miR-208 expression. Overexpression of miR-208 increased basal
      and insulin-mediated VSMC proliferation. Although a miR-208 inhibitor, by itself,
      had no effect on VSMC proliferation, it reduced the insulin-mediated cell
      proliferation. Moreover, miR-208 increased the transformation of cell cycle from
      G0/G1 phase to the S phase. Bioinformatics analysis found that p21, a member of
      the cyclin-dependent kinase (CDK)-inhibitory protein family, may be the target of
      miR-208. Insulin decreased p21 expression in VSMCs; transfection of miR-208 also
      decreased p21 protein expression. In the presence of miR-208 inhibitor, the
      inhibitory effect of insulin on p21 expression in VSMCs was partially blocked.
      The interaction between miR-208 and p21 was direct. Using a luciferase reporter
      with entire wild-type p21 3'UTR or a mutant p21 3'UTR in HEK293 cells, we found
      that miR-208 decreased but neither miR-208 mimic nor the mutant p21 3'UTR had any
      significant effect on the luciferase activity. CONCLUSION: This study indicates
      that miRNAs, miR-208, in particular, are involved in the insulin-induced VSMC
      proliferation via downregulation of its potential target, p21, a key member of
      CDK-inhibitory protein family.

PMID- 21720272
TI  - Novel mechanism of salt-induced glomerular injury: critical role of eNOS and
      angiotensin II.
AB  - OBJECTIVES: The present study was undertaken to examine the role of endothelial
      nitric oxide synthase (eNOS) in salt-sensitive renal injury. METHODS: The effects
      of high-salt diet on renal injury were compared between wild-type and eNOS-/-
      mice. To examine the role of glomerular angiotensin II and oxidative stress, high
      salt fed eNOS-/- mice were given irbesartan, an angiotensin receptor blocker, or
      tempol, an antioxidant. RESULTS: Four weeks of high-salt diet in wild-type mice,
      which rapidly caused glomerular eNOS activation and subsequent increase in nitric
      oxide, did not at all induce renal injury, indicating that wild-type mice are
      salt-resistant. On the contrary, high-salt diet in eNOS-/- mice, which little
      increased nitric oxide, rapidly increased urinary albumin excretion, followed by
      glomerular macrophage infiltration and glomerular sclerosis. Thus, eNOS
      deficiency caused salt-sensitive glomerular injury. Salt-induced glomerular
      injury in eNOS-/- mice was preceded by rapid enhancement of glomerular superoxide
      followed by enhancement of glomerular endothelial angiotensinogen and angiotensin
      II. Irbesartan and tempol, independently of blood pressure, markedly prevented
      salt-induced glomerular injury in eNOS-/- mice, and these protective effects were
      attributed to the attenuation of glomerular oxidative stress and glomerular
      angiotensinogen-derived angiotensin II. CONCLUSION: We propose that eNOS
      dysfunction plays a causative role in salt-induced glomerular injury, through
      augmentation of glomerular oxidative stress-induced angiotensinogen.

PMID- 21720273
TI  - Blood pressure change and outcome in acute ischemic stroke: the impact of
      baseline values, previous hypertensive disease and previous antihypertensive
      treatment.
AB  - BACKGROUND: Management of blood pressure (BP) in acute ischemic stroke is
      controversial. The present study aims to explore the association between baseline
      BP levels and BP change and outcome in the overall stroke population and in
      specific subgroups with regard to the presence of arterial hypertensive disease
      and prior antihypertensive treatment. METHODS: All patients registered in the
      Acute STroke Registry and Analysis of Lausanne (ASTRAL) between 2003 and 2009
      were analyzed. Unfavorable outcome was defined as modified Rankin score more than
      2. A local polynomial surface algorithm was used to assess the effect of BP
      values on outcome in the overall population and in predefined subgroups. RESULTS:
      Up to a certain point, as initial BP was increasing, optimal outcome was seen
      with a progressively more substantial BP decrease over the next 24-48 h. Patients
      without hypertensive disease and an initially low BP seemed to benefit from an
      increase of BP. In patients with hypertensive disease, initial BP and its
      subsequent changes seemed to have less influence on clinical outcome. Patients
      who were previously treated with antihypertensives did not tolerate initially low
      BPs well. CONCLUSION: Optimal outcome in acute ischemic stroke may be determined
      not only by initial BP levels but also by the direction and magnitude of
      associated BP change over the first 24-48 h.

PMID- 21720270
TI  - Blood pressure control and knowledge of target blood pressure in coronary
      patients across Europe: results from the EUROASPIRE III survey.
AB  - BACKGROUND: Blood pressure management is a key issue among patients with coronary
      heart disease (CHD). The present study aimed to identify particular patient
      groups that may need to be specifically targeted in secondary prevention of CHD.
      METHODS: EUROASPIRE III is a cross-sectional study conducted in 2006-2007 among
      patients up to 80 years of age hospitalized for CHD. Patients from 76 centres in
      22 European regions were examined on average 15 months after hospitalization.
      Logistic regression analysis was applied to investigate factors associated with
      blood pressure control and knowledge of target blood pressure using the cut-point
      of less than 140/90 mmHg. RESULTS: Among 7649 patients using antihypertensive
      medication 50.4% achieved blood pressure control and 49.4% provided accurate
      knowledge of target blood pressure. Obese patients were less likely to show
      controlled blood pressure [odds ratio (OR) 0.72, 95% confidence interval (CI)
      0.65-0.80] and accurate knowledge of blood pressure target values (OR 0.80, 95%
      CI 0.72-0.90). Dyslipidaemia was negatively associated with blood pressure
      control and accurate target knowledge. Patients with diabetes mellitus less
      frequently achieved blood pressure control (OR 0.89, 95% CI 0.79-0.99). Accurate
      knowledge of target blood pressure was positively related to blood pressure
      control (OR 1.12, 95% CI 1.00-1.24). Patients who received advice by a health
      professional to reduce salt intake, to reduce weight, and to increase physical
      activity more frequently showed accurate knowledge of blood pressure target
      values. CONCLUSION: Blood pressure control and knowledge of target blood pressure
      are inappropriate in the European high-risk population of coronary patients.
      Particularly CHD patients with obesity, diabetes, and dyslipidaemia need better
      management and control of elevated blood pressure.

PMID- 21720274
TI  - Physician attitudes to blood pressure control: findings from the Supporting
      Hypertension Awareness and Research Europe-wide survey.
AB  - OBJECTIVES: The Supporting Hypertension Awareness and Research Europe-wide
      (SHARE) physician survey aimed to qualify the key challenges that physicians face
      when trying to get patients to blood pressure (BP) goal. METHODS: The SHARE
      survey was open to physicians involved in the treatment of patients with
      hypertension, was anonymous, and was designed to take 15 min to complete. The
      survey included 45 questions covering physicians' demographic information, views
      on the BP targets recommended by the European Society of Hypertension-European
      Society of Cardiology guidelines, opinions on acceptable levels of BP control,
      and perceptions about the challenges associated with getting patients to BP goal.
      RESULTS: The survey was conducted between May and December 2009, and 2629
      European physicians responded. The mean (+/- SD) levels of SBP/DBP that
      physicians were satisfied with, concerned about, or would cause them to take
      immediate action were 131.6  +/-  9.5 /81.9  +/-  5.6, 148.9  +/- 11.3 / 91.6 +/-
      5.8, and 168.2  +/- 17.1 / 100.1  +/-  7.8 mmHg, respectively. Overall, 95.0 and
      90.1% of the physicians, respectively, felt that patients SBP/DBP needed to be
      higher than the guideline recommended goal levels before taking immediate action.
      CONCLUSION: Clinical hesitation in relation to reducing elevated BP to goal
      levels is putting patients at increased cardiovascular risk and contributing to
      the substantial health and economic burden associated with uncontrolled BP. A
      number of strategies are discussed that have been shown to be effective in
      countering this problem.

PMID- 21720275
TI  - Investigation of skin vasoreactivity and blood flow oscillations in hypertensive
      patients: effect of short-term antihypertensive treatment.
AB  - BACKGROUND AND METHOD: In order to evaluate whether arterial hypertension (AH)
      affects skin microcirculation, 46 newly diagnosed, never-treated, hypertensive
      patients and 20 healthy normotensive controls underwent a forearm skin
      postocclusive reactive hyperaemia (PORH) test, using laser-Doppler flowmetry
      (LDF). Their resting skin blood flow oscillations (SBFOs) were also investigated
      using wavelet spectral analyses of skin LDF tracings within six frequency
      subintervals in the 0.005-2 Hz spectral range. To evaluate whether
      antihypertensive treatment affects skin microcirculation, the same measurements
      were repeated in 22 of the recruited hypertensive patients after 8 +/- 2 weeks of
      antihypertensive treatment. RESULTS: Significantly reduced PORH, together with
      significantly higher spectral amplitudes within the majority of the investigated
      SBFO subintervals, was found in untreated hypertensive patients compared with
      controls. In the 22 hypertensive patients who completed the follow-up, there was
      a significant increase in PORH after antihypertensive treatment compared with
      before (357 +/- 178 vs. 284 +/- 214%, respectively, P < 0.05). Following
      antihypertensive treatment, the same 22 hypertensive patients did not differ
      significantly from controls either in PORH or in the majority of the investigated
      SBFO frequency subintervals. CONCLUSION: This study showed reduced skin
      vasoreactivity in the hypertensive patients, confirming that antihypertensive
      treatment negatively affects skin microcirculation. The short period of
      efficacious antihypertensive treatment resulted in normalization of skin
      vasoreactivity in hypertensive patients who completed the follow-up, suggesting
      that antihypertensive treatment affects positively skin microcirculation in AH.
      The SBFO increase in untreated hypertensive patients, and its almost complete
      normalization in treated hypertensive patients, suggests that SBFO enhancement in
      untreated hypertensive patients could be an adaptive reversible response to AH.

PMID- 21720276
TI  - In-vivo nitric oxide synthesis is reduced in obese patients with metabolic
      syndrome: application of a novel stable isotopic method.
AB  - OBJECTIVES: Nitric oxide synthesis is declined in cardiovascular and metabolic
      diseases associated with endothelial dysfunction such as type 2 diabetes,
      hypertension or congestive heart failure. The objectives were to validate a novel
      stable isotopic method for the determination of in-vivo nitric oxide synthesis
      and to evaluate differences in nitric oxide synthesis in obese patients with and
      without metabolic syndrome (MetSyn). METHODS: The new method, called oral nitrate
      test (ONT), measured the decay in saliva or urine samples of an oral dose of
      labelled sodium nitrate. The ONT method was compared to a validated method
      (frequent sampling arginine test, FSAT method) in 10 healthy adult volunteers
      (BMI range = 20.8-27.3 kg/m). The accuracy of the saliva ONT method was then
      tested by measuring nitric oxide synthesis in seven healthy, normal weight
      individuals, seven obese patients without MetSyn and seven obese patients with
      MetSyn. RESULTS: The estimated rate of nitric oxide synthesis was 0.63 +/- 0.20
      MUmol/h per kg from the data obtained from saliva, and 0.50 +/- 0.14 MUmol/h per
      kg from urine. The agreement of the saliva ONT method with the FSAT method (Delta
      = +0.02 +/- 0.24; P = 0.79) was superior to the urine ONT method (Delta = -0.11
      +/- 0.20; P = 0.13). Obese patients with MetSyn had a significantly lower nitric
      oxide production rate (0.21 +/- 0.13 MUmol/h per kg; P = 0.009) than healthy
      normal weight individuals (0.63 +/- 0.30 MUmol/h per kg), whereas nitric oxide
      production rate was intermediate in obese patients without MetSyn (0.49 +/- 0.22
      MUmol/h per kg; P = 0.33). CONCLUSION: The advantages of the new saliva ONT
      method are its accuracy, sensitivity and lack of invasiveness, which could make
      it a reference method for the assessment of in-vivo rates of whole-body nitric
      oxide synthesis.

PMID- 21720277
TI  - Resting cardiopulmonary function in Paralympic athletes with cervical spinal cord
      injury.
AB  - PURPOSE: The purposes of this study were to describe resting cardiopulmonary
      function in highly trained athletes with cervical spinal cord injury (SCI) and to
      compare the data with able-bodied (AB) control subjects. METHODS: Twelve
      Paralympic wheelchair rugby players with cervical SCI (injury level = C5-C7) and
      12 AB controls matched for age, stature, and body mass were assessed for
      pulmonary function using spirometry, body plethysmography, and maximal
      inspiratory and expiratory mouth pressures; diaphragm function using magnetic
      stimulation of the phrenic nerves; and cardiac function using transthoracic
      echocardiography. RESULTS: Total lung capacity, vital capacity, inspiratory
      reserve volume, and expiratory reserve volume were lower in SCI compared with AB
      (P < 0.01), whereas residual volume was elevated in SCI (P = 0.022). Airway
      resistance and maximal inspiratory mouth pressure were not different between
      groups (P > 0.41), whereas maximal expiratory mouth pressure, maximal
      transdiaphragmatic pressure, and twitch transdiaphragmatic pressure were lower in
      SCI (P < 0.01). Percent predicted total lung capacity was significantly
      correlated with maximal transdiaphragmatic pressure in SCI (r = 0.74), suggesting
      that the pulmonary restriction was a result of diaphragm weakness. Left
      ventricular mass, ejection fraction, stroke volume, and cardiac output were lower
      in SCI (P < 0.04), but early and late filling velocities during diastole were not
      different between groups (P > 0.05). CONCLUSIONS: Highly trained athletes with
      cervical SCI exhibit a restrictive pulmonary defect, weakness of the expiratory
      and diaphragm muscles, atrophy of the heart, and reduced systolic cardiac
      function.

PMID- 21720278
TI  - Prognostic value of Achilles tendon Doppler sonography in asymptomatic runners.
AB  - INTRODUCTION: Midportion Achilles tendinopathy (MPT) is a common problem in
      running athletes. Nevertheless, its etiology is not fully understood, and no
      valid prognostic criterion to predict the development of MPT could be identified
      to date. The purpose of the present study, therefore, was to evaluate whether
      power Doppler ultrasonography (PDU) is a suitable method to identify a
      predisposition to MPT in yet asymptomatic runners. METHODS: At 23 major running
      events, 634 asymptomatic long-distance runners were tested for Achilles tendon
      thickness, vascularization, and structural abnormalities using a high-resolution
      PDU device (Toshiba Aplio SSA-770A/80, 12 MHz). In addition, their medical
      history and anthropometric data were documented. All subjects were contacted 6
      and 12 months later and asked about any new symptoms. The collected anamnestic,
      anthropometric, and ultrasonographic data were subjected to regression analysis
      to determine their predictive value concerning the manifestation of midportion
      Achilles tendon complaints (P < 0.05). RESULTS: The highest odds ratio (OR) for
      manifestation of MPT within 1 yr was found for intratendinous blood flow
      ("neovascularization," OR = 6.9, P < 0.001). An increased risk was also
      identified for subjects with a positive history of Achilles tendon complaints (OR
      = 3.8, P < 0.001). A third relevant parameter, just above the level of
      significance, was a spindle-shaped thickening of the tendon on PDU (Wald chi2 =
      3.42). CONCLUSIONS: PDU detection of intratendinous microvessels in the Achilles
      tendons of healthy runners seems to be a prognostically relevant factor
      concerning the manifestation of symptomatic MPT. This finding lays the foundation
      for an early identification of a predisposition to MPT as well as prophylactic
      intervention in as yet asymptomatic runners.

PMID- 21720279
TI  - The Hot Flush Behavior Scale: a measure of behavioral reactions to menopausal hot
      flushes and night sweats.
AB  - OBJECTIVE: There is increasing interest in the development of nonmedical
      treatments for menopausal hot flushes (HF) and night sweats (NS) and some
      evidence that cognitive behavioral interventions reduce their impact. However,
      the behavioral component of HF/NS is underresearched. This article describes the
      development of the Hot Flush Behavior Scale (HFBehS), a measure of the behavioral
      strategies that women use in response to HF/NS, and reports on the reliability,
      validity, and factor structure of the scale. METHODS: Behavioral items were
      generated from the empirical literature and qualitative studies based on in-depth
      interviews, with the aim of reflecting common behaviors related to HF/NS. A total
      of 140 women who had HF/NS completed the initial measure. Principal components
      analyses were applied to the data, with orthogonal rotation, to determine the
      most coherent and interpretable solution. RESULTS: Exploratory factor analysis
      culminated in an 11-item measure comprising three dimensions: behavioral
      avoidance, practical cooling behaviors, and positive behavioral strategies. The
      Hot Flush Beliefs Scale subscales had reasonable internal consistency, with alpha
      values ranging from 0.59 to 0.76. Validity was supported through correlations
      with measures of HF/NS problem rating and frequency and cognitive measures (HF/NS
      beliefs). CONCLUSIONS: Preliminary analysis of the HFBehS reveals it to be a
      psychometrically sound instrument. The HFBehS is grounded in women's experiences
      and can be used as a measure of behavioral reactions to HF/NS as well as enabling
      more rigorous evaluation of psychological interventions.

PMID- 21720280
TI  - Effects of the levonorgestrel-releasing intrauterine system plus estrogen therapy
      in perimenopausal and postmenopausal women: systematic review and meta-analysis.
AB  - OBJECTIVE: The objective of this study was to compare the effects of the
      levonorgestrel-releasing intrauterine system (LNG-IUS) with those of systemic
      progestogen in perimenopausal and postmenopausal women taking systemic estrogen
      therapy (ET). METHODS: We searched Medline (August 8, 2009), Embase (August 8,
      2009), the Cochrane Central Register of Controlled Trials on the Cochrane Library
      Issue 3 (2009), the MetaRegister of Controlled Trials, and the reference lists of
      articles for relevant trials. Randomized controlled studies of LNG-IUS versus
      systemic progestogen in perimenopausal and postmenopausal women taking ET were
      included in the review. Two reviewers abstracted the trials independently. Any
      disagreement was resolved through discussion with the third reviewer. For
      dichotomous outcomes, a Peto odds ratio was calculated. For continuous outcomes,
      nonskewed data from valid scales were synthesized using a weighted mean
      difference or a standardized mean difference. RESULTS: Six trials with a total of
      518 participants were included. The methodological limitation was an attrition
      bias. In perimenopausal and postmenopausal women taking ET, the incidence of a
      proliferative endometrium was comparable between the use of systemic progestogen
      and LNG-IUS, except for sequential medroxyprogesterone acetate, which had a
      higher incidence of proliferative endometrium. Descriptive data synthesis showed
      that ET combined with either LNG-IUS or systemic progestogen effectively relieved
      climacteric symptoms. Vaginal bleeding and spotting were common in the LNG-IUS
      group for the first 3 to 6 months of use. The discontinuation rate was not
      different. There was insufficient evidence to draw any conclusions about the
      other outcomes. CONCLUSIONS: The LNG-IUS was more effective than sequential
      medroxyprogesterone acetate but was comparable with other systemic progestogen
      regimens for endometrial protection in perimenopausal and postmenopausal women
      taking ET.

PMID- 21720281
TI  - Vitamin D deficiency in septic patients at ICU admission is not a mortality
      predictor.
AB  - BACKGROUND: Vitamin D is involved in immune regulation in humans. Vitamin D serum
      deficiency is reported to be common in hospitalized patients, especially among
      Intensive Care Unit (ICU) patients. Our aim was to evaluate the relationship
      between vitamin D levels in septic patients and outcome. METHODS: A total of 170
      patients were studied, of which 92 were severe sepsis/septic shock patients, and
      72 were major trauma patients, as an age-matched control group. Exclusion
      criteria were: age <18 years (y), malnutrition state, pregnancy, breast feeding,
      chemotherapy, immunotherapy, pathologies affecting bone and calcium metabolism,
      vitamin D metabolism derangement for therapy, hematological and solid
      malignancies, and HIV. Vitamin D levels were measured by radioimmunoassay at
      admission. RESULTS: Median vitamin D levels at admission to ICU were 10.1 ng/mL
      in the sepsis group and 18.4 ng/mL in the trauma group (P<0.0001). In univariate
      analysis, mortality rate in septic patients was significantly correlated with
      age, gender, SAPS II, vitamin D level at admission, duration of mechanical
      ventilation, and ICU/hospital length of stay, however, the multivariate logistic
      regression model confirmed significance only for age. CONCLUSION: In our cohort,
      septic patients showed a significantly lower vitamin D level than trauma patients
      in comparison to age cohort patients with the same demographic/clinical
      characteristics, but no clear relationship between vitamin D level and outcome
      was found. Further studies with larger samples are needed to clarify the
      prognostic role of vitamin D and nutraceutical interventions in critically ill
      patients.

PMID- 21720282
TI  - Behind the ESPEN Guidelines on parenteral nutrition in the ICU.
AB  - Enteral nutrition (EN) is a well established approach to nutritional support in
      the ICU. Parenteral nutrition (PN) represents an additional safe approach,
      substituting or complementing EN when its delivery fails completely or partially.
      This article attempts to summarize the ESPEN guidelines of PN in the ICU based on
      the available literature, which is often limited due to quality and methodology
      heterogeneity; the recommendations are therefore largely expressed as expert
      opinions.

PMID- 21720283
TI  - ITalian Observational Study of the management of mild-to-moderate Post-Operative
      Pain (ITOSPOP).
AB  - BACKGROUND: The multicenter observational ITalian Observational Study on the
      management of mild-to-moderate PostOperative Pain (ITOSPOP) was carried out in 24
      hospitals to describe current postoperative pain management in Italy and the
      intensity of pain experienced by patients during the first 48 hours after
      surgery. METHODS: Adult patients, after surgery expected to result in mild
      moderate postoperative pain, underwent six evaluations. The primary endpoint was
      the level of organization and standardization of postoperative pain management.
      Secondary objectives included the intensity of postoperative pain, and an
      assessment of incident pain, postoperative analgesic and concomitant treatment
      administration. RESULTS: Only 16.7% hospitals had an acute pain service and 41.7%
      hospitals applied a standardized protocol for postoperative pain management. The
      majority (>60%) of the 1952 patients monitored underwent all six assessments,
      >70% of which were performed by a physician. The proportion of patients with
      moderate pain decreased during the study period, but almost 10% of patients still
      experienced moderate pain at study end. Mild pain was reported by 50% of the
      patients for the entire study duration. At the final assessment, 5% of patients
      still presented with incident pain frequently interfering with daily activities.
      Most patients were treated with analgesics, but 20% of patients did not receive
      any pain medications despite experiencing pain. CONCLUSION: The level of
      organization and standardization of postoperative pain management in Italian
      hospitals remains low. Postoperative analgesic treatment remained suboptimal and
      almost two-thirds of patients continued to experience pain.

PMID- 21720284
TI  - [Organization of remote long-term support of the patients with cochlear implants
      in distant regions].
AB  - The concept of remote long-term support of the patients with cochlear implants is
      suggested to cope with the problem of the increasingly growing number of patients
      with cochlear pathology. The authors deem it necessary to provide intraoperative
      support and postoperative follow-up technologies for the patients living far from
      the cochlear implantation centres. A scheme for the remote selection of patients
      and their intraoperative monitoring is proposed with the use of implant
      telemetry, electrical stapedial reflex (eSRT) testing, auditory response
      telemetry (ART), and surgical on-line counseling. Remote follow-up and
      rehabilitation should include cochlear implant tuning, speech therapy, and on
      line workshops for the patients and/or specialists. The choice and the use of
      software and hardware for this purpose are discussed. The concept of remote long
      term support turned out to be an efficacious, reliable, time-saving, and cost
      effective tool for providing high-tech medical aid to patients with ENT diseases
      in the Krasnoyarsk kray (territory).

PMID- 21720285
TI  - [The role of environmental factors in the development of pathology of the
      lymphadenoid pharyngeal ring in children].
AB  - The authors present the analysis of the prevalence and structure of pathology of
      the lymphadenoid pharyngeal ring in children living in the districts of the city
      of Krasnoyarsk differing in terms of atmospheric pollution. It is shown that that
      pharyngeal adenoid hypertrophy occurs significantly more frequently in the
      children from the districts exposed to an extremely high level of atmospheric
      pollution than in those residing under more favourable environmental conditions.

PMID- 21720286
TI  - [Dynamics of immunological characteristics and investigation of apoptosis of
      palatal tonsillar lymphocytes in patients presenting with chronic tonsillitis and
      treated by conservative therapy].
AB  - The enhanced amount of viable lymphocytes and the decreased number of apoptotic
      cells as well as the reduced levels of IgA and IgM and the elevated concentration
      of sIgA in lacunar secretion are considered to be the reliable criteria for the
      efficacy of the conservative treatment of chronic tonsillitis. Combined therapy
      of this condition including irrigation of the palatal tonsillar lacunae with a
      miramistin solution, their contact ultrasonic treatment, and application of
      imudon makes it possible to maintain the optimal ratio of viable to apoptotic
      lymphocytes during a period of up to 6-7 months.

PMID- 21720287
TI  - [A new approach to the evaluation of the state of the microcirculatory system in
      patients presenting with chronic atrophic pharyngitis and treated with a
      synthetic neuropeptide].
AB  - This paper is devoted to the mechanisms of development of chronic atrophic
      pharyngitis. A method is proposed for studying microcirculation in the mucous
      membrane at the posterior pharyngeal wall of the patients with this condition
      using laser Doppler flowmetry. The role of chronic somatic pathology in the
      development of pharyngeal dystrophy is demonstrated. It is shown that therapy
      with the synthetic neuropeptide is highly efficacious for the treatment of
      chronic atrophic pharyngitis.

PMID- 21720288
TI  - [The surgical treatment of gunshot wounds on the neck].
AB  - The author summarizes the original experience with the surgical treatment of
      gunshot wounds on the neck with reference to the specific approaches for the
      purpose dictated by the marked variability of the clinical course. An active
      surgical strategy is proposed depending on the character of tissue lesions, the
      form and direction of the wound canal.

PMID- 21720289
TI  - [Clinical studies of vestibular myogenic potentials].
AB  - This paper is focused on the patterns of evoked vestibular myogenic potentials
      associated with the involvement of different segments of the the sacculo-neck
      reflex arc. Specifically, lesions of the vestibular analyzer at the receptor
      level, changes in the transmission system and at the muscular level are
      considered. Various patterns of evoked vestibular myogenic potentials
      characteristic of the disturbance of a given segments of the sacculo-neck reflex
      arc are described.

PMID- 21720290
TI  - [The functional state of the auditory analyzer in prematurely born infants (after
      29 weeks of gestation) at 6 months of life].
AB  - The objective of the present study was to evaluate the functional state of the
      auditory analyzer in infants born prematurely (after 29 weeks of gestation) and
      examined at 6 months of life. The evoked otoacoustic emission (EOAE) techniques
      were used for the purpose. Testing with the help of two different modes of EOAE
      yielded virtually identical results which confirms the possibility to apply both
      delayed EOAE (dEOAE) and distortion-product frequency OAE (dpOAE) for the
      assessment of the auditory function. It is concluded that the degree of cochlear
      development in prematurely born infants (after 29 weeks of gestation) examined by
      the dpOAE technique at 6 months of life is significantly different from that in
      children born between the gestation age of 33 and 37 weeks.

PMID- 21720291
TI  - [The results of audiological examination of children presenting with
      sensorineural loss of hearing due to GJB2 gene mutations during the first year of
      life].
AB  - One of the topical problems of modern pediatric audiology is early diagnostics of
      congenital sensorineural loss of hearing in children and their timely
      rehabilitation. The objective of the present study was to obtain audiological
      characteristics of sensorineural hearing impairment associated with GJB2 gene
      mutations in children during the first year of life. The methods used were
      registration of short-latency auditory evoked potentials (slAEP) and the
      otoacoustic emission (OAE) techniques. The study included 66 children at the age
      of several months presenting with bilateral sensorineural loss of hearing who
      were available for the examination by an otorhinolaryngologist, tympanometry,
      slAEP recording, delayed EOAE (dEOAE) and distortion-product frequency OAE
      (dpOAE) techniques, and genetic counseling. The examination was carried out in
      duplicate, with an interval of 3 months. The genotype containing GJB2 gene
      mutations was identified in 47 (71.2%) children. The 35delG mutation was found in
      41; in 31 of them it occurred in the homozygous state and in 10 in the
      heterozygous state. In the latter group, 8 children had the 35delG mutation in
      the compound heterozygous state together with one more mutation. Six children
      turned out to carry a pathological genotype with other GJB2 gene mutations. It
      was shown that OAE fails to be recorded in most patients with hearing impairment
      due to GJB2 gene mutations during the first months of life. The authors conclude
      that these mutations usually lead to the development of persistent bilateral
      symmetric sensorineural loss of hearing.

PMID- 21720292
TI  - [Functional multispiral computed tomography of sound-transmitting structures in
      the middle ear].
AB  - The objective of this work was to estimate the potential of functional
      multispiral computed tomography (fMSCT) for the choice and planning of the
      treatment strategy and the extent of surgical intervention in the patients
      presenting with fibroosseous diseases of the middle ear associated with the
      pathologically altered mobility of the auditory ossicles. Studies with the use of
      MSCT and fMSCT for the examination of temporal bones in 21 patients (25
      observations) provided information about normal CT anatomy of the middle ear and
      a basis for the development of the fMSCT protocol; moreover they allowed the
      range of mobility of the auditory ossicles to be determined in healthy subjects
      and patients with middle ear disorders. It is concluded that fMSCT of temporal
      bones may be recommended to patients suffering otosclerosis, tympanosclerosis,
      and adhesive otitis media. The use of this technique improves the accuracy of
      diagnosis and facilitates the choice and planning of the treatment strategy and
      the extent of surgical intervention in the patients presenting with middle ear
      diseases.

PMID- 21720293
TI  - [The results of stapedoplasty with the use of an auricular autocartilage as a
      stapes bone prosthesis in the patients presenting with a mixed form of
      otosclerosis].
AB  - The authors present immediate and long-term results of stapedoplasty with the use
      of an auricular autocartilage as a stapes bone prosthesis in 52 patients
      presenting with mixed (types I and II) otosclerosis. The surgical procedure is
      described in considerable detail. The average bone-conduction auditory threshold
      was shown to slightly increase depending on the duration of the disease (less
      than and over 15 years): by 5 dB and 9 dB in mixed otosclerosis of types I and II
      respectively. Mean values of the bone-conduction auditory threshold before and
      after surgery were not significantly different depending on the localization of
      otosclerotic foci in patients with the mixed (types I and II) disease (affecting
      the annular ligament and the base of the stapes bone in 20 patients; annular
      ligament, base of the stapes, and promontory in 32 ones). The average bone-air
      gap (BAG) in the early and late observation periods did not exceed 10 dB in
      either form of otosclerosis which suggests high efficacy of the surgical
      treatment given to the patients in the present study.

PMID- 21720294
TI  - [Application of platelet-enriched plasma for the prevention of cochleovestibular
      disorders associated with piston stapedoplasty].
AB  - The present study was designed to evaluate the influence of sealing the
      labyrinthine vestibule with platelet-enriched plasma (PEP) on the development of
      cochleovestibular complications following piston stapedoplasty. The platelet-rich
      plasma was prepared by single-step centrifugation of the whole venous blood.
      Analysis of the data obtained showed that the use of PEP for sealing the
      periprosthetic space after stapedoplasty reduces the risk of development of
      sensorineural hearing impairment compared with the application of fatty tissue
      for the same purpose or a freely positioned prosthesis. Moreover, the use of PEP
      decreases the probability of the development of tympanophonia and its intensity
      after piston stapedoplasty.

PMID- 21720295
TI  - [Specific features of laryngeal paresis following surgical treatment of diffuse
      toxic goiter (a prospective longitudinal passive study)].
AB  - Specific manifestations of postoperative laryngeal paresis observed with the use
      of indirect laryngoscopy are described in 53 patients subjected to the surgical
      treatment of diffuse toxic goiter. Laryngeal paresis was shown to develop both in
      the early (up to 7 days) and in the late (over 14 days) postoperative periods.
      The delayed form of pathology accounted for 13% of the total number of the cases
      of postoperative laryngeal paresis. The standard treatment of transient
      postoperative laryngeal paresis resulted in the complete recovery of vocal cord
      mobility within 1-6 months after the onset of therapy, regardless of the state of
      the cords at the time of diagnosis of the disease. Persistent postoperative
      laryngeal paresis developed by the end of the 15 month observation period.
      Phonation was found to be preserved in 66% of the patients in whom laryngeal
      paresis (unilateral abduction paresis) had been diagnosed by indirect
      laryngoscopy. In all the remaining patients, phonation recovered 15 months or
      more after surgery. The authors argue that neither the recovery nor the
      preservation of phonation can be a criterion for the absence of complications.
      Also, the outcome of surgical intervention unsupported by the results of
      laryngoscopy performed within 1, 6, and 15 months after the treatment does not
      reflect the true structure of postoperative complications.

PMID- 21720296
TI  - [Peculiarities of ENT diseases in young subjects].
AB  - The results of outpatient medical examination of the applicants and students of
      the Moscow State Institute of International Relations carried out by
      otorhinolaryngologists during the past 12 years are reported. A total of 32,238
      subjects aged from 15 to 25 years were recruited into the project. When
      appropriate, it was supplemented by a combination of audiological studies and
      microbiological analysis of naso- and oropharyngeal secretion. Protocols of
      preventive medical examination and treatment of young subjects presenting with
      acute and chronic inflammatory ENT diseases are proposed.

PMID- 21720297
TI  - [Prospects for the use of histaminergic preparations for the purpose of noise
      otoprotection].
AB  - The objective of the present study was to experimentally evaluate the
      otoprotective effect of the histaminergic preparation betagistin dihydrochloride
      given at a dose of 32 mg to 10 healthy male volunteers aged from 18 to 22 (mean
      19.4) years who were exposed to 85 dB "white" nose for 1 hour. The functional
      state of their auditory system was estimated from the results of investigations
      including determination of the tonal auditory threshold, delayed evoked
      otoacoustic emission and distortion-product frequency otoacoustic emission, short
      latency evoked auditory potentials, and extratympanic electrocochleography. It
      was shown that betagistin dihydrochloride produced a well-apparent otoprotective
      effect over the entire range of tests comprehensively characterizing the
      functional state of the cochlea. It is concluded that betagistin dihydrochloride
      has good prospects for the application in a variety of production activities (to
      treat occupational noise-induced pathology) including aerospace medicine.

PMID- 21720298
TI  - [Reconstruction of the auricle for grade II microtia].
AB  - Results of the surgical treatment of 28 patients presenting with grade II
      microtia are presented. Otoplasty with the use of a free dermocartilaginous graft
      harvested from the normal auricle by the method of G.V. Kuchinsky was performed
      in 3 cases, correction of grade II plical folding of the pinna as described by
      A.T. Gruzdeva in 14 cases, and correction of grade III plical folding of the
      pinna as proposed by J. Diffenbach in 11 cases. Six cases of grade II microtia
      were treated by the original otoplastic technique. The results of the surgical
      treatment presented in this paper are discussed with special reference to
      differential modalities for the correction of auricular deformities considered in
      the present study.

PMID- 21720299
TI  - [The efficacy of sinuforte in the starting monotherapy of the patients presenting
      with acute rhinosinusitis].
AB  - The present randomized open study included 30 patients with acute suppurative
      rhinosinusitis. The efficacy of the treatment was estimated from the dynamics of
      the patients' subjective sensations and the objective assessment of clinical
      manifestations of the disease on days 1, 3, 5, and 7 after the onset of therapy.
      All the patients were prescribed treatment with sinuforte (one dose administered
      daily into each half of the nasal cavity at one and the same time). It was shown
      that monotherapy with sinuforte for the treatment of patients presenting with
      acute suppurative rhinosinusitis of moderate severity ensured the recovery in 73%
      of the cases.

PMID- 21720300
TI  - [Necrotizing (malignant) external otitis].
AB  - Five cases of necrotizing (malignant) external otitis were diagnosed during 25
      years (from 1984 to 2009). All the patients aged from 60 to 80 years presented
      with diabetes mellitus. Blue pus bacilli were isolated from the ear canal. One of
      the 5 patients had bilateral external otitis. All the five underwent radical
      surgery after conservative therapy had proved inefficient. The treatment
      completed, the patients were discharged from the hospital in good clinical
      condition.

PMID- 21720303
TI  - Warfarin-related nephropathy: another newly recognized complication of an old
      drug.
AB  - Since its approval in the 1950s, warfarin has been the most often prescribed
      anticoagulant, with attendant risks of bleeding. Brodsky et al. describe another
      potential complication of warfarin therapy. Warfarin-related nephropathy (WRN)
      has been described in patients with chronic kidney disease and appears to
      accelerate the rate of progression and increase the risk of death. The
      interactions between warfarin and chronic kidney disease are complex, and the
      recognition of the potential complications is expanding.

PMID- 21720304
TI  - AGE-RAGE interaction and oxidative stress in obesity-related renal dysfunction.
AB  - Obesity is a risk factor for development of kidney disease. Advanced glycation
      end products (AGEs) and the receptor for AGEs (RAGE) play important roles in the
      pathogenesis of renal disorders that are not associated with diabetes. Harcourt
      et al. provide evidence to support the mechanism responsible for AGE-RAGE
      interaction and the downstream oxidative stress and inflammation in obesity
      related dysfunction. These findings might provide a new strategy for kidney
      disease in obesity.

PMID- 21720305
TI  - WNT/beta-catenin signaling in polycystic kidney disease.
AB  - Cystic kidney diseases have been linked to defective WNT signal transduction.
      Perturbations of cystic disease genes cause activation of canonical WNT/beta
      catenin/TCF/Lef1 signaling in model organisms and cultured cells. Inappropriate
      levels of WNT/beta-catenin signaling cause renal cyst formation in mice. These
      observations have prompted the idea that an activation of WNT/beta-catenin
      signaling may constitute a common causative event in cyst formation. Now this
      view is challenged by key genetic mouse models of cystic kidney disease that do
      not display WNT/beta-catenin activity in cyst-lining epithelia.

PMID- 21720306
TI  - Methotrexate in the urine.

PMID- 21720307
TI  - Racial and ethnic differences in the prevalence of placenta previa.
AB  - OBJECTIVE: The objective of this study is to determine the prevalence of placenta
      previa among different racial and ethnic groups. STUDY DESIGN: We conducted a
      retrospective cohort study to examine the prevalence of placenta previa among
      five major racial and ethnic groups: African American, Asian, Caucasian, Hispanic
      and Native American. We included all deliveries >= 20 weeks gestation from a
      large northern Californian Health Maintenance Organization from 1995-2006. A
      multivariable logistic regression model was used to control for potential
      confounders. RESULT: Of the 394 083 deliveries in our cohort, 1580 (0.40%) were
      complicated by placenta previa. The prevalence of placenta previa was: Asian
      0.64%, Native American 0.60%, African American 0.44%, Caucasian 0.36%, Hispanic
      0.34% and unknown 0.31% (P<0.001). In our multivariable logistic regression
      model, only Asians (odds ratio (OR) 1.73, 95% confidence intervals (CI) 1.53
      1.95) and African Americans (OR 1.43, 95% CI 1.19-1.72) were at increased risk
      for having placenta previa, compared with Caucasians. CONCLUSION: Asian women
      have the highest prevalence of placenta previa.

PMID- 21720308
TI  - Preparation of cyclodextrin chiral stationary phases by organic soluble catalytic
      'click' chemistry.
AB  - We describe an effective and simple protocol that uses click chemistry to attach
      native beta-cyclodextrin (beta-CD) to silica particles, resulting in a chiral
      stationary phase (CCNCSP) that can be used for the enantioseparation of chiral
      drugs by high-performance liquid chromatography (HPLC). Starting from beta-CD,
      the CCNCSP is prepared in several steps: (i) reaction of beta-CD with 1-(p
      toluenesulfonyl)-imidazole to afford mono-6-toluenesulfonyl-beta-CD; (ii)
      azidolysis of mono-6-toluenesulfonyl-beta-CD in dimethylformamide to give mono-6
      azido-beta-CD (N(3)-CD); (iii) reaction of cuprous iodide with triphenylphosphine
      to form an organic soluble catalyst CuI(PPh(3)); (iv) preparation of alkynyl
      modified silica particles; and (v) click chemistry immobilization of N(3)-CD onto
      alkynyl-modified silica to afford the desired chiral stationary phase. Synthesis
      of the stationary phase and column packing takes ~1 week.

PMID- 21720309
TI  - Simultaneous in vitro molecular screening of protein-peptide interactions by flow
      cytometry, using six Bcl-2 family proteins as examples.
AB  - The B-cell lymphoma-2 (Bcl-2) family contains six antiapoptotic members, each
      with a hydrophobic pocket in which Bcl-2 homology region 3 (BH3) helices bind.
      This binding quenches apoptotic signals from activated BH3 family members. Many
      tumor cells either have increased expression of one of these six proteins or
      become overexpressed under treatment. Six fusion proteins made up of glutathione
      S-transferase and each of the Bcl-2 members are bound individually to six
      glutathione bead sets, each set being easily distinguished by its different
      intensity of red fluorescence. The coated bead sets are washed, combined and
      incubated with green fluorescent Bim-BH3 peptide and a small molecule in 10-MUl
      wells for 1 h. The green fluorescence signal for each bead set is resolved, and
      selective inhibitors are expected to reduce the signal for individual bead sets.
      Each 384-well plate is analyzed in 12 min, measuring 200 of 2,000 beads (~10%) of
      each type per well.

PMID- 21720310
TI  - Magnetic-based purification of untouched mouse germinal center B cells for ex
      vivo manipulation and biochemical analysis.
AB  - Detailed biochemical analysis of unmanipulated germinal center (GC) B cells has
      not been achieved. Previously, we designed and used a simple, economical and new
      magnetic bead separation scheme for the purification of 'untouched' mature GC and
      non-GC B cells from the spleens of immunized mice and reported the first
      biochemical assessment of the signaling cascades that contribute to cyclin D
      stability and GC B cell proliferation. Here we provide a detailed protocol for
      the method we used, which involves preparing single-cell suspension from the
      spleens of immunized mice, followed by labeling of nontarget cells with
      biotinylated antibodies specific for CD43, CD11c and IgD (for GC enrichment) or
      GL7 (for non-GC enrichment); these steps are followed by cell depletion using
      standard magnetic bead technology. This protocol can yield GC and non-GC B cells
      with purities exceeding 90%. The sorting process can be carried out in ~1 h and
      provides a population of GC B cells of sufficient purity and quantity to allow ex
      vivo manipulation, including biochemical and genetic analysis as well as cell
      culture.

PMID- 21720311
TI  - The validated embryonic stem cell test to predict embryotoxicity in vitro.
AB  - In the embryonic stem cell test (EST), differentiation of mouse embryonic stem
      cells (mESCs) is used as a model to assess embryotoxicity in vitro. The test was
      successfully validated by the European Center for the Validation of Alternative
      Methods (ECVAM) and models fundamental mechanisms in embryotoxicity, such as
      cytotoxicity and differentiation. In addition, differences in sensitivity between
      differentiated (adult) and embryonic cells are also taken into consideration. To
      predict the embryotoxic potential of a test substance, three endpoints are
      assessed: the inhibition of differentiation into beating cardiomyocytes, the
      cytotoxic effects on stem cells and the cytotoxic effects on 3T3 fibroblasts. A
      special feature of the EST is that it is solely based on permanent cell lines so
      that primary embryonic cells and tissues from pregnant animals are not needed. In
      this protocol, we describe the ECVAM-validated method, in which the morphological
      assessment of contracting cardiomyocytes is used as an endpoint for
      differentiation, and the molecular-based FACS-EST method, in which highly
      predictive protein markers specific for developing heart tissue were selected.
      With these methods, the embryotoxic potency of a compound can be assessed in
      vitro within 10 or 7 d, respectively.

PMID- 21720312
TI  - Recording of mechanosensitive currents using piezoelectrically driven
      mechanostimulator.
AB  - Mechanotransduction constitutes the basis of a variety of physiological
      processes, such as the senses of touch, balance, proprioception and hearing. In
      vertebrates, mechanosensation is mediated by mechanosensory receptors. The
      aptitude of these mechanoreceptors for detecting mechanical information relies on
      the presence of mechanosensitive channels that transform mechanical forces into
      electrical signals. However, advances in understanding mechanical transduction
      processes have proven difficult because sensory nerve endings have historically
      been inaccessible to patch-clamp recording. We report here an in vitro model of
      mechanotransduction that allows the application of focal force on sensory neuron
      membrane during whole-cell patch clamping. This technique, called mechano-clamp,
      provides an opportunity to explore the properties and identities of
      mechanotransducer channels in mammalian sensory neurons. The protocol-from tissue
      dissociation to patch-clamp recording-can be completed in 7 h.

PMID- 21720313
TI  - Direct stochastic optical reconstruction microscopy with standard fluorescent
      probes.
AB  - Direct stochastic optical reconstruction microscopy (dSTORM) uses conventional
      fluorescent probes such as labeled antibodies or chemical tags for subdiffraction
      resolution fluorescence imaging with a lateral resolution of ~20 nm. In contrast
      to photoactivated localization microscopy (PALM) with photoactivatable
      fluorescent proteins, dSTORM experiments start with bright fluorescent samples in
      which the fluorophores have to be transferred to a stable and reversible OFF
      state. The OFF state has a lifetime in the range of 100 milliseconds to several
      seconds after irradiation with light intensities low enough to ensure minimal
      photodestruction. Either spontaneously or photoinduced on irradiation with a
      second laser wavelength, a sparse subset of fluorophores is reactivated and their
      positions are precisely determined. Repetitive activation, localization and
      deactivation allow a temporal separation of spatially unresolved structures in a
      reconstructed image. Here we present a step-by-step protocol for dSTORM imaging
      in fixed and living cells on a wide-field fluorescence microscope, with standard
      fluorescent probes focusing especially on the photoinduced fine adjustment of the
      ratio of fluorophores residing in the ON and OFF states. Furthermore, we discuss
      labeling strategies, acquisition parameters, and temporal and spatial resolution.
      The ultimate step of data acquisition and data processing can be performed in
      seconds to minutes.

PMID- 21720314
TI  - Rapid characterization of complex viscous samples at molecular levels by neutral
      desorption extractive electrospray ionization mass spectrometry.
AB  - In this protocol, the sample (which could be a bulk or heterogeneous fluid, or a
      greasy surface) is treated with a neutral desorption (ND) sampling gas beam, and
      the resulting analyte mixtures are directly characterized by extractive
      electrospray ionization mass spectrometry (EESI-MS). The ND device can be
      specifically constructed such that the sampling gas beam is bubbled through the
      liquid sample (microjet sampling) or directed to impact the sample surface (e.g.,
      for the analysis of a material like cheese). The ND-EESI-MS analysis process
      requires no sample pretreatment because it can tolerate an extremely complex
      matrix. ND-EESI-MS allows real-time, online chemical profiling of highly viscous
      samples under ambient conditions. Both volatile and nonvolatile analytes from
      viscous samples can easily be detected and quantified by ND-EESI-MS, thereby
      providing an MS-based analytical platform for multiple disciplines (e.g., for the
      food industry, for drug discovery, and for the biological and life sciences).
      Here we describe the ND-EESI-MS protocol for viscous sample analysis, including
      the experimental design, equipment setup, reagent preparation, data acquisition
      and analysis steps. The data collection process takes <1 min per sample, although
      the time required for the whole procedure, which largely depends on the
      experimental preparation processes, might be considerably longer.

PMID- 21720315
TI  - Linear amplification for deep sequencing.
AB  - Linear amplification for deep sequencing (LADS) is an amplification method that
      produces representative libraries for Illumina next-generation sequencing within
      2 d. The method relies on attaching two different sequencing adapters to blunt
      end repaired and A-tailed DNA fragments, wherein one of the adapters is extended
      with the sequence for the T7 RNA polymerase promoter. Ligated and size-selected
      DNA fragments are transcribed in vitro with high RNA yields. Subsequent cDNA
      synthesis is initiated from a primer complementary to the first adapter, ensuring
      that the library will only contain full-length fragments with two distinct
      adapters. Contrary to the severely biased representation of AT- or GC-rich
      fragments in standard PCR-amplified libraries, the sequence coverage in T7
      amplified libraries is indistinguishable from that of nonamplified libraries.
      Moreover, in contrast to amplification-free methods, LADS can generate sequencing
      libraries from a few nanograms of DNA, which is essential for all applications in
      which the starting material is limited.

PMID- 21720316
TI  - Fabrication of synthetic polymer coatings and their use in feeder-free culture of
      human embryonic stem cells.
AB  - The culture of human embryonic stem (hES) cells in defined and xenogeneic-free
      conditions will contribute substantially to future biotechnological and medical
      applications. To achieve this goal, we developed the first fully defined
      synthetic polymer coating poly[2-(methacryloyloxy)ethyl dimethyl-(3
      sulfopropyl)ammonium hydroxide] (PMEDSAH) that sustains long-term growth of hES
      cells in different culture media. Here we describe a detailed protocol for the
      reproducible fabrication of PMEDSAH coating on tissue culture polystyrene dishes,
      and for the feeder-free culture of hES cells on PMEDSAH coating in defined
      culture medium. This culture system represents a key step toward the fully
      defined and xenogeneic-free culture of hES cells.

PMID- 21720317
TI  - Embryonic and induced pluripotent stem cell staining and sorting with the live
      cell fluorescence imaging probe CDy1.
AB  - Detecting and isolating specific types of cells is crucial to understanding a
      variety of biological processes, including development, aging, regeneration and
      pathogenesis; this understanding, in turn, allows the use of cells for
      therapeutic purposes, for which stem cells have emerged recently as invaluable
      materials. The current methods of isolation and characterization of stem cells
      depend on cell morphology in culture or on immunostaining of specific markers.
      These methods are, however, time consuming and involve the use of antibodies that
      may often make the cells unsuitable for further study. We recently developed a
      fluorescent small molecule named CDy1 (compound of designation yellow 1) that
      selectively stains live embryonic stem cells (ESCs) and induced pluripotent stem
      cells (iPSCs). This protocol describes detailed procedures for staining ESC and
      iPSC in live conditions and for fluorescence-activated cell sorting (FACS) of ESC
      using CDy1. Cell staining, image acquisition and FACS can be done within 6 h.

PMID- 21720318
TI  - Reproducible subcutaneous transplantation of cell sheets into recipient mice.
AB  - Perfecting tissue engineering and cell sheet transplantation is an important step
      toward realizing regenerative medicine and is a growing area of research. Before
      being applied to clinical settings, it is important that these approaches are
      evaluated in vivo. Here we provide a detailed protocol for handling thin cell
      sheets, for a simple and highly reproducible subcutaneous transplantation of cell
      sheets into mice, and for the histological examination of regenerated tissues.
      Various aspects of transplants can be assessed, such as maintenance,
      differentiation and proliferation. An emphasis is placed on surgical precision
      and reproducibility. The resulting consistency between surgeries helps minimize
      artifacts from surgical variation and therefore enables researchers to not only
      observe and compare the interactions between host tissues but also to compare
      transplants among different host animals. A single transplantation can be carried
      out within ~10 min.

PMID- 21720320
TI  - Shot with its own gun.

PMID- 21720319
TI  - Procedures for large-scale metabolic profiling of serum and plasma using gas
      chromatography and liquid chromatography coupled to mass spectrometry.
AB  - Metabolism has an essential role in biological systems. Identification and
      quantitation of the compounds in the metabolome is defined as metabolic
      profiling, and it is applied to define metabolic changes related to genetic
      differences, environmental influences and disease or drug perturbations.
      Chromatography-mass spectrometry (MS) platforms are frequently used to provide
      the sensitive and reproducible detection of hundreds to thousands of metabolites
      in a single biofluid or tissue sample. Here we describe the experimental workflow
      for long-term and large-scale metabolomic studies involving thousands of human
      samples with data acquired for multiple analytical batches over many months and
      years. Protocols for serum- and plasma-based metabolic profiling applying gas
      chromatography-MS (GC-MS) and ultraperformance liquid chromatography-MS (UPLC-MS)
      are described. These include biofluid collection, sample preparation, data
      acquisition, data pre-processing and quality assurance. Methods for quality
      control-based robust LOESS signal correction to provide signal correction and
      integration of data from multiple analytical batches are also described.

PMID- 21720321
TI  - Made in Japan.

PMID- 21720322
TI  - A helping hand.

PMID- 21720323
TI  - Give the new generation a chance.

PMID- 21720335
TI  - Averting a swarm.

PMID- 21720336
TI  - Stem-cell scientists grapple with clinics.

PMID- 21720338
TI  - Biologist spared jail for grant fraud.

PMID- 21720337
TI  - Call to curb lab tests on dogs.

PMID- 21720339
TI  - Okinawa goes recruiting.

PMID- 21720341
TI  - Science in Africa: The view from the front line.

PMID- 21720342
TI  - Science in Africa: Enter the dragon.

PMID- 21720343
TI  - Science in Africa: The wheat stalker.

PMID- 21720344
TI  - Africa AIMS high.

PMID- 21720345
TI  - Research in a war zone.

PMID- 21720346
TI  - Crowd control in Rwanda.

PMID- 21720351
TI  - WHO working to be fit for purpose.

PMID- 21720352
TI  - More at stake in stem-cell patents.

PMID- 21720353
TI  - Population bomb: the UN responds.

PMID- 21720354
TI  - Block changes to Brazil's Forest Code.

PMID- 21720355
TI  - Rosalyn Sussman Yalow (1921-2011).

PMID- 21720356
TI  - Microbiology: Arms race in a drop of sea water.

PMID- 21720357
TI  - Cosmology: A monster in the early Universe.

PMID- 21720358
TI  - Quantum optics: Atom gives light a subtle squeeze.

PMID- 21720359
TI  - Regenerative medicine: Muscle for a damaged heart.

PMID- 21720360
TI  - Molecular physics: Matter-wave interference made clear.

PMID- 21720361
TI  - HIV: Going for the watchman.

PMID- 21720362
TI  - Atomic physics and quantum optics using superconducting circuits.
AB  - Superconducting circuits based on Josephson junctions exhibit macroscopic quantum
      coherence and can behave like artificial atoms. Recent technological advances
      have made it possible to implement atomic-physics and quantum-optics experiments
      on a chip using these artificial atoms. This Review presents a brief overview of
      the progress achieved so far in this rapidly advancing field. We not only discuss
      phenomena analogous to those in atomic physics and quantum optics with natural
      atoms, but also highlight those not occurring in natural atoms. In addition, we
      summarize several prospective directions in this emerging interdisciplinary
      field.

PMID- 21720363
TI  - Morphological evolution caused by many subtle-effect substitutions in regulatory
      DNA.
AB  - Morphology evolves often through changes in developmental genes, but the causal
      mutations, and their effects, remain largely unknown. The evolution of naked
      cuticle on larvae of Drosophila sechellia resulted from changes in five
      transcriptional enhancers of shavenbaby (svb), a transcript of the ovo locus that
      encodes a transcription factor that governs morphogenesis of microtrichiae,
      hereafter called 'trichomes'. Here we show that the function of one of these
      enhancers evolved through multiple single-nucleotide substitutions that altered
      both the timing and level of svb expression. The consequences of these nucleotide
      substitutions on larval morphology were quantified with a novel functional assay.
      We found that each substitution had a relatively small phenotypic effect, and
      that many nucleotide changes account for this large morphological difference. In
      addition, we observed that the substitutions had non-additive effects. These data
      provide unprecedented resolution of the phenotypic effects of substitutions and
      show how individual nucleotide changes in a transcriptional enhancer have caused
      morphological evolution.

PMID- 21720364
TI  - Genomic island variability facilitates Prochlorococcus-virus coexistence.
AB  - Prochlorococcus cyanobacteria are extremely abundant in the oceans, as are the
      viruses that infect them. How hosts and viruses coexist in nature remains
      unclear, although the presence of both susceptible and resistant cells may allow
      this coexistence. Combined whole-genome sequencing and PCR screening technology
      now enables us to investigate the effect of resistance on genome evolution and
      the genomic mechanisms behind the long-term coexistence of Prochlorococcus and
      their viruses. Here we present a genome analysis of 77 substrains selected for
      resistance to ten viruses, revealing mutations primarily in non-conserved,
      horizontally transferred genes that localize to a single hypervariable genomic
      island. Mutations affected viral attachment to the cell surface and imposed a
      fitness cost to the host, manifested by significantly lower growth rates or a
      previously unknown mechanism of more rapid infection by other viruses. The mutant
      genes are generally uncommon in nature yet some carry polymorphisms matching
      those found experimentally. These data are empirical evidence indicating that
      viral-attachment genes are preferentially located in genomic islands and that
      viruses are a selective pressure enhancing the diversity of both island genes and
      island gene content. This diversity emerges as a genomic mechanism that reduces
      the effective host population size for infection by a given virus, thus
      facilitating long-term coexistence between viruses and their hosts in nature.

PMID- 21720366
TI  - A luminous quasar at a redshift of z = 7.085.
AB  - The intergalactic medium was not completely reionized until approximately a
      billion years after the Big Bang, as revealed by observations of quasars with
      redshifts of less than 6.5. It has been difficult to probe to higher redshifts,
      however, because quasars have historically been identified in optical surveys,
      which are insensitive to sources at redshifts exceeding 6.5. Here we report
      observations of a quasar (ULAS J112001.48+064124.3) at a redshift of 7.085, which
      is 0.77 billion years after the Big Bang. ULAS J1120+0641 has a luminosity of 6.3
      * 10(13)L(?) and hosts a black hole with a mass of 2 * 10(9)M(?) (where L(?) and
      M(?) are the luminosity and mass of the Sun). The measured radius of the ionized
      near zone around ULAS J1120+0641 is 1.9 megaparsecs, a factor of three smaller
      than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone
      transmission profile is consistent with a Lyalpha damping wing, suggesting that
      the neutral fraction of the intergalactic medium in front of ULAS J1120+0641
      exceeded 0.1.

PMID- 21720367
TI  - Observation of squeezed light from one atom excited with two photons.
AB  - Single quantum emitters such as atoms are well known as non-classical light
      sources with reduced noise in the intensity, capable of producing photons one by
      one at given times. However, the light field emitted by a single atom can exhibit
      much richer dynamics. A prominent example is the predicted ability of a single
      atom to produce quadrature-squeezed light, which has fluctuations of amplitude or
      phase that are below the shot-noise level. However, such squeezing is much more
      difficult to observe than the emission of single photons. Squeezed beams have
      been generated using macroscopic and mesoscopic media down to a few tens of
      atoms, but despite experimental efforts, single-atom squeezing has so far escaped
      observation. Here we generate squeezed light with a single atom in a high-finesse
      optical resonator. The strong coupling of the atom to the cavity field induces a
      genuine quantum mechanical nonlinearity, which is several orders of magnitude
      larger than in typical macroscopic media. This produces observable quadrature
      squeezing, with an excitation beam containing on average only two photons per
      system lifetime. In sharp contrast to the emission of single photons, the
      squeezed light stems from the quantum coherence of photon pairs emitted from the
      system. The ability of a single atom to induce strong coherent interactions
      between propagating photons opens up new perspectives for photonic quantum logic
      with single emitters.

PMID- 21720368
TI  - Quantum quench of Kondo correlations in optical absorption.
AB  - The interaction between a single confined spin and the spins of an electron
      reservoir leads to one of the most remarkable phenomena of many-body physics--the
      Kondo effect. Electronic transport measurements on single artificial atoms, or
      quantum dots, have made it possible to study the effect in great detail. Here we
      report optical measurements on a single semiconductor quantum dot tunnel-coupled
      to a degenerate electron gas which show that absorption of a single photon leads
      to an abrupt change in the system Hamiltonian and a quantum quench of Kondo
      correlations. By inferring the characteristic power-law exponents from the
      experimental absorption line shapes, we find a unique signature of the quench in
      the form of an Anderson orthogonality catastrophe, induced by a vanishing overlap
      between the initial and final many-body wavefunctions. We show that the power-law
      exponent that determines the degree of orthogonality can be tuned using an
      external magnetic field, which unequivocally demonstrates that the observed
      absorption line shape originates from Kondo correlations. Our experiments
      demonstrate that optical measurements on single artificial atoms offer new
      perspectives on many-body phenomena previously studied using transport
      spectroscopy only.

PMID- 21720365
TI  - Integrated genomic analyses of ovarian carcinoma.
AB  - A catalogue of molecular aberrations that cause ovarian cancer is critical for
      developing and deploying therapies that will improve patients' lives. The Cancer
      Genome Atlas project has analysed messenger RNA expression, microRNA expression,
      promoter methylation and DNA copy number in 489 high-grade serous ovarian
      adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these
      tumours. Here we report that high-grade serous ovarian cancer is characterized by
      TP53 mutations in almost all tumours (96%); low prevalence but statistically
      recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2,
      RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter
      methylation events involving 168 genes. Analyses delineated four ovarian cancer
      transcriptional subtypes, three microRNA subtypes, four promoter methylation
      subtypes and a transcriptional signature associated with survival duration, and
      shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1
      aberrations have on survival. Pathway analyses suggested that homologous
      recombination is defective in about half of the tumours analysed, and that NOTCH
      and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

PMID- 21720369
TI  - Modern optics in exceptionally preserved eyes of Early Cambrian arthropods from
      Australia.
AB  - Despite the status of the eye as an "organ of extreme perfection", theory
      suggests that complex eyes can evolve very rapidly. The fossil record has, until
      now, been inadequate in providing insight into the early evolution of eyes during
      the initial radiation of many animal groups known as the Cambrian explosion. This
      is surprising because Cambrian Burgess-Shale-type deposits are replete with
      exquisitely preserved animals, especially arthropods, that possess eyes. However,
      with the exception of biomineralized trilobite eyes, virtually nothing is known
      about the details of their optical design. Here we report exceptionally preserved
      fossil eyes from the Early Cambrian (~ 515 million years ago) Emu Bay Shale of
      South Australia, revealing that some of the earliest arthropods possessed highly
      advanced compound eyes, each with over 3,000 large ommatidial lenses and a
      specialized 'bright zone'. These are the oldest non-biomineralized eyes known in
      such detail, with preservation quality exceeding that found in the Burgess Shale
      and Chengjiang deposits. Non-biomineralized eyes of similar complexity are
      otherwise unknown until about 85 million years later. The arrangement and size of
      the lenses indicate that these eyes belonged to an active predator that was
      capable of seeing in low light. The eyes are more complex than those known from
      contemporaneous trilobites and are as advanced as those of many living forms.
      They provide further evidence that the Cambrian explosion involved rapid
      innovation in fine-scale anatomy as well as gross morphology, and are consistent
      with the concept that the development of advanced vision helped to drive this
      great evolutionary event.

PMID- 21720370
TI  - Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1
      protein.
AB  - Macrophages and dendritic cells have key roles in viral infections, providing
      virus reservoirs that frequently resist antiviral therapies and linking innate
      virus detection to antiviral adaptive immune responses. Human immunodeficiency
      virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to
      transduce macrophages, due to an as yet uncharacterized mechanism that inhibits
      infection by interfering with efficient synthesis of viral complementary DNA. In
      contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce
      myeloid cells efficiently owing to their virion-associated Vpx accessory
      proteins, which counteract the restrictive mechanism. Here we show that the
      inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD
      domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus
      infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin
      ligase, leading to highly efficient proteasome-dependent degradation of the
      protein. Mutations in SAMHD1 cause Aicardi-Goutieres syndrome, a disease that
      produces a phenotype that mimics the effects of a congenital viral infection.
      Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutieres
      syndrome results in inappropriate triggering of innate immune responses via
      cytosolic nucleic acids sensors. Thus, our findings show that macrophages are
      defended from HIV-1 infection by a mechanism that prevents an unwanted interferon
      response triggered by self nucleic acids, and uncover an intricate relationship
      between innate immune mechanisms that control response to self and to retroviral
      pathogens.

PMID- 21720372
TI  - Accessibility to spinal cord injury care worldwide: the need for poverty
      reduction.

PMID- 21720374
TI  - Out-of-the-box thinking.

PMID- 21720375
TI  - Heartening results: the CUPID gene therapy trial for heart failure.

PMID- 21720378
TI  - Shedding new light on the mechanism underlying stem cell therapy for the heart.

PMID- 21720379
TI  - iPSCs: Unstable origins?

PMID- 21720380
TI  - Switching on the lights: the use of optogenetics to advance retinal gene therapy.

PMID- 21720382
TI  - Impact of TP53 mutation and 17p deletion in mantle cell lymphoma.

PMID- 21720383
TI  - Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial
      chemotherapy for aggressive B-cell lymphomas: phase I study.
AB  - Lenalidomide was shown to have significant single-agent activity in relapsed
      aggressive non-Hodgkin's lymphoma (NHL). We conducted a phase I trial to
      establish the maximum tolerated dose of lenalidomide that could be combined with
      R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone).
      Eligible patients were adults with newly diagnosed, untreated CD20 positive
      diffuse large cell or follicular grade III NHL. Patients received oral
      lenalidomide on days 1-10 with standard dose R-CHOP every 21 days. All patients
      received pegfilgrastim on day 2 of the cycle and aspirin prophylaxis. The
      lenalidomide dose levels tested were 15, 20 and 25 mg. A total of 24 patients
      were enrolled. The median age was 65 (35-82) years and 54% were over 60 years.
      Three patients received 15 mg, 3 received 20 mg and 18 received 25 mg of
      lenalidomide. No dose limiting toxicity was found, and 25 mg on days 1-10 is the
      recommended dose for phase II. The incidence of grade IV neutropenia and
      thrombocytopenia was 67% and 21%, respectively. Febrile neutropenia was rare (4%)
      and there were no toxic deaths. The overall response rate was 100% with a
      complete response rate of 77%. Lenalidomide at the dose of 25 mg/day administered
      on days 1 to 10 of 21-day cycle can be safely combined with R-CHOP in the initial
      chemotherapy of aggressive B-cell lymphoma.

PMID- 21720384
TI  - The miR 302-367 cluster drastically affects self-renewal and infiltration
      properties of glioma-initiating cells through CXCR4 repression and consequent
      disruption of the SHH-GLI-NANOG network.
AB  - Glioblastoma multiforme (GBM) is the most common form of primary brain tumor in
      adults, often characterized by poor survival. Glioma-initiating cells (GiCs) are
      defined by their extensive self-renewal, differentiation, and tumor initiation
      properties. GiCs are known to be involved in tumor growth and recurrence, and in
      resistance to conventional treatments. One strategy to efficiently target GiCs in
      GBM consists in suppressing their stemness and consequently their tumorigenic
      properties. In this study, we show that the miR-302-367 cluster is strongly
      induced during serum-mediated stemness suppression. Stable miR-302-367 cluster
      expression is sufficient to suppress the stemness signature, self-renewal, and
      cell infiltration within a host brain tissue, through inhibition of the CXCR4
      pathway. Furthermore, inhibition of CXCR4 leads to the disruption of the sonic
      hedgehog (SHH)-GLI-NANOG network, which is involved in self-renewal and
      expression of the embryonic stem cell-like signature. In conclusion, we
      demonstrated that the miR-302-367 cluster is able to efficiently trigger a
      cascade of inhibitory events leading to the disruption of GiCs stem-like and
      tumorigenic properties.

PMID- 21720385
TI  - VDAC1 selectively transfers apoptotic Ca2+ signals to mitochondria.
AB  - Voltage-dependent anion channels (VDACs) are expressed in three isoforms, with
      common channeling properties and different roles in cell survival. We show that
      VDAC1 silencing potentiates apoptotic challenges, whereas VDAC2 has the opposite
      effect. Although all three VDAC isoforms are equivalent in allowing mitochondrial
      Ca(2+) loading upon agonist stimulation, VDAC1 silencing selectively impairs the
      transfer of the low-amplitude apoptotic Ca(2+) signals. Co-immunoprecipitation
      experiments show that VDAC1, but not VDAC2 and VDAC3, forms complexes with IP(3)
      receptors, an interaction that is further strengthened by apoptotic stimuli.
      These data highlight a non-redundant molecular route for transferring Ca(2+)
      signals to mitochondria in apoptosis.

PMID- 21720386
TI  - Jagged2 controls the generation of motor neuron and oligodendrocyte progenitors
      in the ventral spinal cord.
AB  - In the developing spinal cord, motor neurons (MNs) and oligodendrocytes arise
      sequentially from a common pool of progenitors. However, the genetic network
      responsible for this neurogenesis to gliogenesis switch is largely unknown. A
      transcriptome analysis identified the Notch ligand Jagged2 (JAG2) as a Sonic
      hedgehog-regulated factor transiently expressed in MN progenitors (pMNs). In vivo
      loss- and gain-of-function experiments show that JAG2 schedules the
      differentiation of the pMN progenitors. At early developmental stages, Olig2
      expressing pMN progenitors that enter the differentiation pathway exclusively
      generate MNs. At these times, the activation of the Notch pathway by JAG2
      maintains selected pMN progenitors in an undifferentiated state by two
      mechanisms; first it inhibits MN generation by reducing Olig2 proteins levels,
      and second it directly inhibits the premature generation of oligodendrocyte
      progenitors (OLPs) by maintaining high levels of Hes5. Later, extinction of JAG2
      from the pMN results in the loss of Hes5 expression, heralding the gliogenic
      phase of pMN progenitors. Strikingly, downregulation of JAG2 in pMN progenitors
      is sufficient to promote the precocious generation of OLPs. Together these data
      provide evidence that JAG2 is a key regulator of the timely and ordered
      generation of two of the defining cell types in the spinal cord, MNs and OLPs.

PMID- 21720387
TI  - Immunity against Staphylococcus aureus cutaneous infections.
AB  - Complications arising from cutaneous and soft tissue infections with
      Staphylococcus aureus are a major clinical problem owing to the high incidence of
      these infections and the widespread emergence of antibiotic-resistant bacterial
      strains. If prophylactic vaccines or immunotherapy for certain patient
      populations are to be developed as an alternative to antibiotics, it will be
      essential to better understand the immune mechanisms that provide protection
      against S. aureus skin infections. Recent discoveries have identified a key role
      for interleukin-1 (IL-1)- and IL-17-mediated immune responses in promoting
      neutrophil recruitment to the site of infection in the skin, a process that is
      required for host defence and bacterial clearance. This Review describes these
      new insights and discusses their potential impact on immune-based therapies and
      vaccination strategies.

PMID- 21720388
TI  - The association of phosphoinositide 3-kinase enhancer A with hepatic insulin
      receptor enhances its kinase activity.
AB  - Dysfunction of hepatic insulin receptor tyrosine kinase (IRTK) causes the
      development of type 2 diabetes. However, the molecular mechanism regulating IRTK
      activity in the liver remains poorly understood. Here, we show that
      phosphoinositide 3-kinase enhancer A (PIKE-A) is a new insulin-dependent enhancer
      of hepatic IRTK. Liver-specific Pike-knockout (LPKO) mice display glucose
      intolerance with impaired hepatic insulin sensitivity. Specifically, insulin
      provoked phosphoinositide 3-kinase/Akt signalling is diminished in the liver of
      LPKO mice, leading to the failure of insulin-suppressed gluconeogenesis and
      hyperglycaemia. Thus, hepatic PIKE-A has a key role in mediating insulin signal
      transduction and regulating glucose homeostasis in the liver.

PMID- 21720389
TI  - In vivo study in Trypanosoma brucei links mitochondrial transfer RNA import to
      mitochondrial protein import.
AB  - Trypanosoma brucei imports all mitochondrial transfer RNAs (tRNAs) from the
      cytosol. By using cell lines that allow independent tetracycline-inducible RNA
      interference and isopropyl-beta-D-thiogalactopyranoside-inducible expression of a
      tagged tRNA, we show that ablation of Tim17 and mitochondrial heat-shock protein
      70, components of the inner-membrane protein translocation machinery, strongly
      inhibits import of newly synthesized tRNAs. These findings, together with
      previous results in yeast and plants, suggest that the requirement for
      mitochondrial protein-import factors might be a conserved feature of
      mitochondrial tRNA import in all systems.

PMID- 21720390
TI  - SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity.
AB  - Acetaminophen/paracetamol-induced liver failure--which is induced by the binding
      of reactive metabolites to mitochondrial proteins and their disruption--is
      exacerbated by fasting. As fasting promotes SIRT3-mediated mitochondrial-protein
      deacetylation and acetaminophen metabolites bind to lysine residues, we
      investigated whether deacetylation predisposes mice to toxic metabolite-mediated
      disruption of mitochondrial proteins. We show that mitochondrial deacetylase
      SIRT3(-/-) mice are protected from acetaminophen hepatotoxicity, that
      mitochondrial aldehyde dehydrogenase 2 is a direct SIRT3 substrate, and that its
      deacetylation increases acetaminophen toxic-metabolite binding and enzyme
      inactivation. Thus, protein deacetylation enhances xenobiotic liver injury by
      modulating the binding of a toxic metabolite to mitochondrial proteins.

PMID- 21720392
TI  - Single-cell profiling sheds new light.

PMID- 21720391
TI  - Our microbial selves: what ecology can teach us.
AB  - Advances in DNA sequencing have allowed us to characterize microbial communities-
      including those associated with the human body--at a broader range of spatial and
      temporal scales than ever before. We can now answer fundamental questions that
      were previously inaccessible and use well-tested ecological theories to gain
      insight into changes in the microbiome that are associated with normal
      development and human disease. Perhaps unsurprisingly, the ecosystems associated
      with our body follow trends identified in communities at other sites and scales,
      and thus studies of the microbiome benefit from ecological insight. Here, we
      assess human microbiome research in the context of ecological principles and
      models, focusing on diversity, biological drivers of community structure, spatial
      patterning and temporal dynamics, and suggest key directions for future research
      that will bring us closer to the goal of building predictive models for
      personalized medicine.

PMID- 21720393
TI  - Excitement mounts for first disease-modifying cystic fibrosis drugs.

PMID- 21720395
TI  - Market watch: upcoming market catalysts in Q3 2011.

PMID- 21720396
TI  - Deal watch: Phase III antibody targeting tumour pH acquired in Prometheus deal.

PMID- 21720398
TI  - Alan Aderem. Interview with Asher Mullard.

PMID- 21720399
TI  - Timing of patent filing and market exclusivity.

PMID- 21720400
TI  - Cancer: Autophagy presents Achilles heel in melanoma.

PMID- 21720401
TI  - Inflammatory disorders: Steroids modulate microglia-mediated inflammation.

PMID- 21720402
TI  - Metabolic disease: New role for HDACs in glucose homeostasis.

PMID- 21720403
TI  - Obesity and diabetes: An antidiabetic phospholipid.

PMID- 21720405
TI  - Analgesia: Flower power.

PMID- 21720406
TI  - Bridging the efficacy-effectiveness gap: a regulator's perspective on addressing
      variability of drug response.
AB  - Drug regulatory agencies should ensure that the benefits of drugs outweigh their
      risks, but licensed medicines sometimes do not perform as expected in everyday
      clinical practice. Failure may relate to lower than anticipated efficacy or a
      higher than anticipated incidence or severity of adverse effects. Here we show
      that the problem of benefit-risk is to a considerable degree a problem of
      variability in drug response. We describe biological and behavioural sources of
      variability and how these contribute to the long-known efficacy-effectiveness
      gap. In this context, efficacy describes how a drug performs under conditions of
      clinical trials, whereas effectiveness describes how it performs under conditions
      of everyday clinical practice. We argue that a broad range of pre- and post
      licensing technologies will need to be harnessed to bridge the efficacy
      effectiveness gap. Successful approaches will not be limited to the current
      notion of pharmacogenomics-based personalized medicines, but will also entail the
      wider use of electronic health-care tools to improve drug prescribing and patient
      adherence.

PMID- 21720408
TI  - Pseudoexfoliative deposits on an intraocular lens implant.

PMID- 21720407
TI  - Bio-inspired, bioengineered and biomimetic drug delivery carriers.
AB  - Synthetic carriers such as polymer and lipid particles often struggle to meet
      clinical expectations. Natural particulates - that range from pathogens to
      mammalian cells - are therefore worth examining in more depth, as they are highly
      optimized for their specific functions in vivo and possess features that are
      often desired in drug delivery carriers. With a better understanding of these
      biological systems, in conjunction with the availability of advanced
      biotechnology tools that are useful for re-engineering the various natural
      systems, researchers have started to exploit natural particulates for multiple
      applications in the delivery of proteins, small interfering RNA and other
      therapeutic agents. Here, we review the natural drug delivery carriers that have
      provided the basis and inspiration for new drug delivery systems.

PMID- 21720409
TI  - Microbial profile and antibiotic susceptibility of culture-positive bacterial
      endophthalmitis.

PMID- 21720410
TI  - Congenital innervation dysgenesis syndrome (CID)/congenital cranial
      dysinnervation disorders (CCDDs).
AB  - Congenital loss of innervation to the extra-ocular muscles (EOMs) can have a
      profound effect on the target muscle. This has been well recognised in Duane's
      retraction syndrome. However, it has been less emphasised in other congenital
      oculo-motor disorders. Such congenital ocular motor defects have been expanded to
      include DRS, congenital fibrosis of EOMs, monocular elevation defect, Mobius
      syndrome, as well as several other non-ocular muscles supplied by cranial nerves
      such as facial muscles. Such loss of innervation to motor muscles can be unified
      as a defined clinical entity, which can be labelled as congenital innervation
      dysgenesis syndrome or CID for short. CID may also affect other muscles supplied
      by nerves other than the cranial nerves and may be sensory as well as motor.

PMID- 21720411
TI  - Acute lymphocytic leukemia relapsing as bilateral serous retinal detachment: a
      case report.

PMID- 21720412
TI  - Psychological distress in people with disfigurement from facial palsy.
AB  - AIMS: Psychological distress is well documented in people with facial
      disfigurement. However, the prevalence of psychological distress in patients with
      facial palsy has not been studied. This study aims to establish the prevalence of
      psychological distress and the extent of anxiety and depression in a sample of
      facial palsy patients from the Northwest of England. METHOD: A total of 103
      participants with facial palsy completed a questionnaire pack comprising the
      Illness Perception Questionnaire-Revised (IPQ-R), a demographic questionnaire,
      and the Hospital Anxiety and Depression Scale (HADS). The severity of
      participants' facial palsy was measured by the House-Brackmann scale. RESULTS: In
      all, 32.7 and 31.3% of the sample had significant levels of anxiety and
      depression, respectively. The mean age of participants was 59, and 35.9% had
      grade 6 facial palsy. Significant associations were found between participants'
      perception of consequences, duration, timeline, and the level of distress. No
      significant associations were found between clinical severity of facial palsy and
      levels of distress. Females had significantly higher levels of anxiety compared
      with males. CONCLUSIONS: There was a significant level of distress in this study
      group. The levels of psychological distress were higher than the levels found in
      other outpatient attenders. There were significant associations between
      participants' illness perceptions and their level of distress.

PMID- 21720413
TI  - Recurrent intradialytic elevation of intraocular pressure in a case of
      neovascular glaucoma.

PMID- 21720414
TI  - An unusual eyelid lump: unsuspected embedded contact lens for up to 40 years. Two
      cases and literature review.
AB  - The purpose of this study is to report two patients with retained rigid gas
      permeable contact lenses (RCLs) that had become integrated into the upper eyelid
      tissues, to provide a brief literature review and to discuss possible
      aetiologies. The methods used in this study are as follows: retrospective review
      of clinical records and review of the literature. Two contact lens wearers
      presented with an upper eyelid mass, one after previous loss of a lens and the
      other 40 years after a failed trial of RCL wear; this latter case appears to be
      the longest delay in diagnosis reported in the ophthalmic literature. Although
      extremely rare, the presence of an upper tarsal lump in a RCL wearer should raise
      possibility of an embedded contact lens, particularly where the contour is
      suggestive in size or shape. Ultrasonography or magnetic resonance imaging may
      show characteristic changes. It is probable that RCL migration into periocular
      tissues occurs by entrapment above the upper tarsal border and integration, by
      local tissue necrosis, into the tarsus or pretarsal space.

PMID- 21720415
TI  - Application of multifocal visual evoked potentials in the assessment of visual
      dysfunction in macular diseases.
AB  - PURPOSE: To evaluate the use of AccuMap multifocal visual evoked potentials
      (mfVEP) in visual dysfunction caused by macular diseases. METHODS: Forty-eight
      eyes with known macular diseases underwent AccuMap mfVEP and microperimetry 1
      (MP1) assessments. Evaluation of mfVEP abnormality was based on an amplitude
      deviation probability plot and the AccuMap Severity Index (ASI). Correlation
      analyses of the mean mfVEP amplitude corresponding to a radius of 2 degrees , 5
      degrees , and 10 degrees  of the central visual field, minimum angle of
      resolution best-corrected visual acuity (BCVA), and MP1 mean sensitivity of the
      corresponding areas were performed. RESULTS: Among the 48 affected eyes, AccuMap
      mfVEP detected an abnormality of the central visual field in 45 eyes, with a
      sensitivity of 93.8%. The mean mfVEP amplitudes within a radius of 2 degrees , 5
      degrees , and 10 degrees  of the central visual field were found to be positively
      correlated with BCVA (P<0.01 for all groups). The mean amplitudes also positively
      correlated with the MP1 mean sensitivity value of the corresponding visual field
      (P<0.01 for all groups). In the group with stable fixation or predominantly
      central fixation, the mean mfVEP amplitudes did not correlate with the BCVA or
      the MP1 mean sensitivity value. Regardless of the fixation status, the ASI was
      found to correlate with both the BCVA and the total MP1 mean defect value.
      CONCLUSION: Objective perimetry using AccuMap mfVEP might be applied in the
      assessment of macular function, with the ASI offering a potentially useful
      indicator for evaluating macular dysfunction.

PMID- 21720416
TI  - Evaluation of the effectiveness of ophthalmic assistants as screeners for
      glaucoma in North India.
AB  - AIM: To assess whether ophthalmic assistants are effective in screening people
      for glaucoma in India. METHODOLOGY: The study subjects were examined by both
      trained ophthalmic assistants and an ophthalmologist in both hospital and
      community settings. Specific tests for the diagnosis of glaucoma suspects
      included visual field examination using frequency doubling technology perimetry,
      intraocular pressure measurement (Tonopen), A-scan central anterior chamber depth
      measurement and dilated optic disc examination. The findings recorded by the
      ophthalmic assistants were masked to the ophthalmologist to avoid measurement
      bias. RESULTS: In the hospital setting, there was a substantial level of
      agreement between the ophthalmic assistants and the ophthalmologist in the
      diagnosis of glaucoma suspects (89.29%, k=0.7, 95% confidence interval (CI)=0.54
      0.86). The diagnostic accuracy of the ophthalmic assistants in detecting glaucoma
      suspects was high for sensitivity (95.2%, 95% CI=91.4-97.7%) but lower for
      specificity at 71.4% (95% CI=60.0-78.7%).In the community setting, there was a
      moderate level of agreement between the ophthalmic assistants and the
      ophthalmologist in the diagnosis of glaucoma suspects (78.23%, k=0.50, 95%
      CI=0.37-0.64). The diagnostic accuracy of the ophthalmic assistants in detecting
      glaucoma suspects was moderate for sensitivity (82.9, 95% CI=69.7-91.5%) but
      lower for specificity at 76.8% (95% CI=72.7-79.5%). CONCLUSION: Ophthalmic
      assistants can be used for opportunistic case detection of glaucoma suspects in
      the community. Structured training of the ophthalmic assistants together with
      enhanced clinical experience would improve their performance in detecting
      glaucoma suspects in the community.

PMID- 21720417
TI  - Visual and non-visual factors associated with patient satisfaction and quality of
      life in LASIK.
AB  - PURPOSE: The aim of this study was to determine how laser in situ keratomileusis
      (LASIK) affects quality of life (QOL) and to identify factors that may affect
      satisfaction after LASIK. METHODS: A total of 104 patients with a mean age of
      29+/-6, treated with LASIK for myopia and astigmatism, were enrolled in a
      prospective study. High (90%) and low (10%) contrast visual acuity (CVA) were
      measured under photopic and scotopic conditions before surgery and at 3 months
      later. A multidimensional QOL scale (Institute for Eye Research multidimensional
      QOL scale), which assesses psychological characteristics, personality traits,
      cosmesis, frequency, and tolerance to disturbing visual and ocular symptoms, and
      overall satisfaction with vision correction, was also used. Paired rank tests
      were used to compare preoperative and postoperative vision and QOL scores.
      Correlations and a multiple linear regression were used to describe the
      relationship between CVA, QOL, and satisfaction after LASIK. RESULTS: Significant
      postoperative changes included increased satisfaction following LASIK (P<0.001),
      reduced frequency of visual and ocular symptoms (P<0.001), and change in
      psychological characteristics (P=0.033). The change in satisfaction with LASIK
      can be predicted by a combination of preoperative satisfaction, postoperative
      frequency of disturbing visual and ocular symptoms, postoperative mean spherical
      equivalent, and postoperative scotopic high CVA (R (2)=0.725, P<0.05).
      CONCLUSIONS: Satisfaction with LASIK is related to visual function, preoperative
      expectations, psychological characteristics, and uncorrected CVA achieved. An
      increased sense of subjective well-being, adaptability, and self-efficacy was
      evident after LASIK. Patients reported a more optimistic attitude to life and
      increase perceived QOL after surgery.

PMID- 21720418
TI  - Prevalence and risk factors for refractive errors and ocular biometry parameters
      in an elderly Asian population: the Singapore Longitudinal Aging Study (SLAS).
AB  - PURPOSE: To determine the prevalence rates of refractive errors and pattern of
      ocular biometry in a multi-ethnic elderly Asian population. METHODS: A population
      based study of 1835 residents aged 55-85 years, evaluating the refractive error
      and ocular biometry parameters, including axial length (AL) and anterior chamber
      depth. RESULTS: The age-standardized prevalence of myopia, hyperopia,
      astigmatism, and anisometropia were 30.0% (95% confidence interval (CI): 29.6,
      30.4), 41.5% (95% CI: 41.1, 41.9), 43.5% (95% CI: 43.1, 44.0), and 22.1% (95% CI:
      21.7, 22.4), respectively. Male gender (P=0.02), age >= 75 years (P=0.033), and
      higher educational level (P<0.001) were significantly associated with higher
      rates of myopia in multivariate analyses. The prevalence of astigmatism was
      higher in persons with diabetes (odds ratio (OR) 1.4, 95% CI: 1.03, 1.90,
      P=0.031). AL was longer in Chinese than other ethnic groups (23.7 vs 23.4 mm,
      P=0.018), and in men compared with women (24.2 vs 23.4 mm, P<0.001). AL was
      associated with increasing height (AL increased by 0.3 mm for every 10 cm
      increase in height, P<0.001). CONCLUSION: There is a high prevalence of myopia in
      elderly Singaporeans, consistent with trends seen in younger populations in Asia.
      Male gender and higher education were independent risk factors for myopia. These
      data suggest that higher rates of myopia in East Asians compared with Caucasians
      may not be a recent phenomenon.

PMID- 21720419
TI  - Application of mRNA regulatory regions to improve tumor specificity of transgene
      expression.
AB  - Efficiency and specificity are two key attributes of anti-cancer drugs including
      genetic therapeutic agents. We suggest a way to improve specificity of gene
      therapy drugs based on the ability of 3'-untranslated regions (UTR) of some mRNAs
      selectively stabilize transcripts only during cell division. The mRNAs of genes
      encoding DNA methyltransferase I (DNMT1) and topoisomerase IIalpha (TOP2A) are
      among such transcripts. When inserted into genetic constructs designed to produce
      therapeutic protein in tumor cells, such 3'-UTR would lead to diminished effect
      of therapeutic protein on normal cells, which are characterized by low or absent
      proliferative activity. However, when included in gene expression cassette, these
      3'-UTR might result in decreased transgene expression, thus, overweighting the
      advantage of increased specificity of expression. We showed that DNMT1 and to the
      lesser extent TOP2A 3'-UTR do not alter significantly therapeutic transgene
      expression level in tumor cells, thus, confirming the functionality of the
      proposed approach.

PMID- 21720420
TI  - Screening siRNAs targeting a novel gene (HA117) and the development of a
      derivative recombinant adenovirus delivery system.
AB  - A novel gene, HA117, was discovered in our previous work. Using the pSOS-HUS
      vector method which we designed at previous study, we screened for small
      interfering RNAs (siRNAs) that targeted HA117. The pSOS-HUS siRNA screening
      results were verified and a delivery system was developed that contained a
      recombinant adenovirus carrying DNA templates for the transcription of the HA117
      siRNAs. Of five pairs of DNA templates, siRNA transcribed from HAi5 produced the
      strongest effect against HA117. A recombinant adenovirus containing HAi5 (Ad
      HAi5) was successfully constructed and evaluated. This work has laid the
      foundation for further study of HA117 gene function using RNA interference
      technology and has showed the pSOS-HUS vector method was successfully utilized as
      a rapid and effective screen of siRNAs for a target gene.

PMID- 21720421
TI  - The individual and combined effects of glycemic index and protein on glycemic
      response, hunger, and energy intake.
AB  - Although high protein and low glycemic index (GI) foods are thought to promote
      satiety, little is known about the effects of GI, protein, and their interaction
      on hunger and energy intake several hours following a mixed meal. This study
      investigated the long term effects of GI, protein, and their combined effects on
      glucose, insulin, hunger, and energy intake in healthy, sedentary, overweight,
      and obese adults (BMI of 30.9 +/- 3.7 kg/m(2)). Sixteen individuals participated
      separately in four testing sessions after an overnight fast. The majority (75%)
      were non-Hispanic Blacks. Each consumed one of four breakfast meals (high GI/low
      protein, high GI/high protein, low GI/low protein, low GI/high protein) in random
      order. Visual analog scales (VAS) and blood samples were taken at baseline, 15
      min, and at 30 min intervals over 4 h following the meal. After 4 h, participants
      were given the opportunity to consume food ad libitum from a buffet style lunch.
      Meals containing low GI foods produced a smaller glucose (P < 0.002) and insulin
      (P = 0.0001) response than meals containing high GI foods. No main effects for
      protein or interactions between GI and protein were observed in glucose or
      insulin responses, respectively. The four meals had no differential effect on
      observed energy intake or self-reported hunger, satiety, and prospective energy
      intake. Low GI meals produced the smallest postprandial increases in glucose and
      insulin. There were no effects for GI, protein, or their interaction on appetite
      or energy intake 4 h after breakfast.

PMID- 21720422
TI  - Differences in the heritability of growth and growth velocity during infancy and
      associations with FTO variants.
AB  - While the associations of common variants in the FTO gene with obesity have been
      widely replicated in adults, there is conflicting evidence regarding their
      effects in infancy. We hypothesize that the genetic influences on growth traits
      vary during infancy, and that conflicting results may stem from variation in the
      ages at which FTO associations have been examined. Using longitudinal weight and
      length data at 0, 1, 3, 6, 9, 12, 18, 24, 30, and 36 months in 917 (444 females,
      473 males) family members from the Fels Longitudinal Study, we used a variance
      components-based approach (SOLAR) to: (i) examine differences in heritability
      (gene-by-age interaction) in weight, length, relative weight (BMI and ponderal
      index (PI)) and instantaneous weight and length velocities over the course of
      infancy, and (ii) test whether a common FTO variant (rs9939609) was associated
      with infant growth at three ages (maximum trait heritability, birth and 36
      months). All heritabilities at birth (of 39-74%) were significant (P < 3.9 * 10(
      10)), but changed with age (gene-by-age interaction, P < 0.05). Weight, relative
      weight, and weight velocity reached maximum heritabilities (of 76-89%) at 6-9
      months, while length and length velocity reached maximum heritabilities (of 96
      99%) at 18-30 months. We found no association of rs9939609 with growth status or
      velocity measured at any age (P > 0.11). This study for the first time
      demonstrates the fluctuation of genetic influences on infant growth, but further
      work is required to determine which gene variants explain the strong additive
      genetic effects observed.

PMID- 21720423
TI  - Effect of obesity on repeat revascularization in patients undergoing percutaneous
      coronary intervention with drug-eluting stents.
AB  - Obesity is a major risk factor for developing coronary artery disease. The impact
      of obesity on prognosis among those with established coronary disease is less
      clear. The objective of this study was to evaluate the effect of obesity on
      repeat revascularization in patients undergoing percutaneous coronary
      intervention (PCI) with drug-eluting stents (DES). We examined 6,083 patients who
      were divided into three groups according to BMI: normal (BMI 18.5-24.9 kg/m(2), n
      = 1,592); overweight (BMI 25-29.9 kg/m(2), n = 3,026) and obese (BMI >30 kg/m(2),
      n = 1,465). The follow-up focused on clinical-driven repeat revascularization,
      including target lesion revascularization (TLR) and nonTLR. Median follow-up was
      26 months (interquartile range 20-32). There was no significant difference in the
      incidence of TLR among normal, overweight, and obese patients (6.3% vs. 6.1% vs.
      7.1%; P = 0.423). In contrast, the incidence of nonTLR was significantly higher
      in obese patients compared with normal and overweight (8.4% vs. 6.0% vs. 5.8%, P
      = 0.003). Multivariate analysis showed that obesity was an independent predictor
      of nonTLR during follow-up (hazard ratio = 1.39; 95% confidence interval = 1.06
      1.83; P = 0.019), along with diabetes and hypercholesterolemia. Concomitant use
      of statins was independently associated with decreased risk of nonTLR (hazard
      ratio = 0.75; 95% confidence interval = 0.62-0.92; P = 0.005). In conclusion,
      among patients undergoing PCI with DES, obesity was not associated with TLR, but
      was associated with a higher risk of nonTLR.

PMID- 21720424
TI  - Overweight as a prognostic factor in children with acute lymphoblastic leukemia.
AB  - Our purpose was to investigate the prognostic impact of overweight/obesity in 5
      year event-free survival (EFS) in a cohort of children with acute lymphoblastic
      leukemia (ALL). We retrospectively analyzed 181 newly diagnosed ALL children
      enrolled between 1990 and 2009 and treated with Berlin-Frankfurt-Munich (BFM)
      protocols. The majority of children in our cohort were <10 years-old. Our data
      clearly indicated that overweight/obesity is an independent predictor of relapse
      risk, mainly in the intermediate- and high-risk groups (HR) of children. These
      results could be explained by changes in the chemotherapy pharmacokinetics in
      overweight/obese patients and by the antiapoptotic effects in leukemic cells
      caused by adipocytes.

PMID- 21720425
TI  - A nutritional comparison of foods and beverages marketed to children in two
      advertising policy environments.
AB  - Childhood obesity is associated with children's exposure to food/beverage
      marketing. Policy options in this area are being sought in order to reduce
      childhood obesity rates on a population-level. We examined the nutritional
      quality of foods advertised to children during their preferred television viewing
      in Ontario (Canada), where advertising is self-regulated by industry, and in
      Quebec (Canada), where a child-directed advertising ban exists. A total of 428
      children aged 10-12 years completed television viewing diaries for 7 days. Thirty
      two television stations were recorded simultaneously between 6 AM and midnight. A
      content analysis of 90 h of English Ontario, French Quebec, and English Quebec
      children's preferred viewing was then undertaken. A total of 429 food and
      beverage advertisements were analyzed and their nutritional quality was assessed.
      Food advertisements in the Quebec French sample were statistically significantly
      higher in total fat, saturated fat and protein, and lower in carbohydrates and
      sugar per 100 g, and as a percentage of energy than food ads in the two English
      samples. A statistically significantly lower percentage of the Quebec French food
      advertisements were classified as either high fat, sugar or sodium and a smaller
      proportion of food ads were classified as "less healthy" compared to the Ontario
      and Quebec English samples. These results suggest that the Quebec advertising ban
      is influencing the macronutrient profile of advertised foods viewed by French
      Quebec children during their preferred viewing and that their promotions are
      marginally healthier than that viewed by the English samples.

PMID- 21720426
TI  - A randomized pilot trial of a full subsidy vs. a partial subsidy for obesity
      treatment.
AB  - Intensive obesity treatment is mandated by federal health care reform but is
      costly. A partial subsidy for obesity treatment could lower the cost of
      treatment, without reducing its efficacy. This study sought to test whether a
      partial subsidy for obesity treatment would be feasible, as compared to a fully
      subsidized intervention. The study was a pilot randomized trial. Participants (n
      = 50) were primary care patients with obesity and at least one comorbid condition
      (diabetes, hypertension, dyslipidemia, or obstructive sleep apnea). Each
      participant received eight weight loss counseling visits as well as portion
      controlled foods for weight loss. Participants were randomized to full subsidy or
      partial subsidy (2 vs. 1 meal per day provided). The primary outcome was weight
      change after 4 months. Secondary outcomes included changes in blood pressure,
      waist circumference, and health-related quality of life. Participants in the full
      and partial subsidy groups lost 5.9 and 5.3 kg, equivalent to 5.3% and 5.1% of
      initial weight, respectively (P = 0.71). Changes in secondary outcomes were
      similar in the two groups. A partial subsidy was feasible and induced a
      clinically similar amount of weight loss, compared to a full subsidy. Large-scale
      testing of economic incentives for weight control is merited given the federal
      mandate to offer weight loss counseling to obese patients.

PMID- 21720427
TI  - Saliency processing and obesity: a preliminary imaging study of the stop signal
      task.
AB  - Obesity has been associated with altered cerebral functions including cognitive
      control. The stop signal task (SST) has been widely used to study cognitive
      control by producing high conflict stop trials among many low conflict go trials.
      Contrasting these stop trials with go trials provides a measure of saliency
      processing and response inhibition. By comparing functional magnetic resonance
      images of obese (BMI >30) and lean (BMI <22) females performing the SST, we
      observed differences in regional brain activations despite similar behavioral
      performance between groups. Specifically, lean females had greater activations in
      the insula, inferior parietal cortex, cuneus, and supplementary motor area than
      obese females during stop as compared to go trials. This difference was caused by
      diminished brain activations in obese females in stop as compared to go trials.
      Furthermore, the brain activations in these regions inversely correlated to BMI
      across subjects. These preliminary findings suggest altered neural processes of
      cognitive control in obesity.

PMID- 21720428
TI  - Toward an early marker of metabolic dysfunction: omentin-1 in prepubertal
      children.
AB  - Omentin-1 is a recently recognized adipokine primarily originating in visceral
      adipose tissue. We posited that circulating omentin-1 could be an early marker of
      metabolic dysfunction. To this end, we examined the associations between
      circulating omentin-1, body fat (bioelectric impedance), an endocrine-metabolic
      profile (homeostasis model assessment for insulin resistance (HOMA(IR)), serum
      lipids, high-molecular-weight (HMW) adiponectin and blood pressure (BP)) and
      family history of obesity and diabetes in asymptomatic prepubertal children (n =
      161; 77 boys and 84 girls; age 7 +/- 1 year) with a normal distribution of height
      and weight. Increased circulating omentin-1 was associated with a poorer
      metabolic profile, with relatively higher HOMA(IR), fasting triacylglycerol, BP
      and familial prevalence of diabetes (all P < 0.005 to P < 0.0001), and relatively
      lower fraction of HMW adiponectin (P < 0.005), whereas no relationship was found
      with body weight or fat or with family history of obesity. All these associations
      were independent of age, gender and fat mass. In conclusion, circulating omentin
      1 may become a marker of metabolic dysfunction integrating insulin sensitivity,
      markers of adipose-tissue metabolism and BP as early as in prepubertal childhood.

PMID- 21720429
TI  - Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo
      controlled, multicenter trial.
AB  - It is well established that abdominal obesity or upper body fat distribution is
      associated with increased risk of metabolic and cardiovascular disease. The
      purpose of the present study was to determine if a 24 week weight loss program
      with orlistat 60 mg in overweight subjects would produce a greater change in
      visceral adipose tissue (VAT) as measured by computed tomography (CT) scan,
      compared to placebo. The effects of orlistat 60 mg on changes in total fat mass
      (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One
      hundred thirty-one subjects were randomized into a multicenter, double-blind
      placebo controlled study in which 123 subjects received at least one post
      baseline efficacy measurement (intent-to-treat population). Both orlistat-and
      placebo-treated subjects significantly decreased their VAT at 24 weeks with a
      significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%,
      P < 0.05). In addition, orlistat-treated subjects had significantly greater
      weight loss (-5.93 kg vs. -3.94 kg, P < 0.05), total fat mass loss (-4.65 kg vs. 
      3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue
      and content of liver fat compared with placebo-treated subjects. This is the
      first study to demonstrate that orlistat 60 mg significantly reduces VAT in
      addition to total body fat compared to placebo treated subjects after a 24 week
      weight loss program. These results suggest that orlistat 60 mg may be an
      effective weight loss tool to reduce metabolic risk factors associated with
      abdominal obesity.

PMID- 21720430
TI  - Liver attenuation, pericardial adipose tissue, obesity, and insulin resistance:
      the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - Insulin resistance is linked to general and abdominal obesity, but its relation
      to hepatic lipid content and pericardial adipose tissue is less clear. The
      purpose of this study was to examine cross-sectional associations of liver
      attenuation, pericardial adipose tissue, BMI, and waist circumference with
      insulin resistance. We measured liver attenuation and pericardial adipose tissue
      using the existing cardiac computed tomography scans in 5,291 individuals free of
      clinical cardiovascular disease and diabetes in the Multi-Ethnic Study of
      Atherosclerosis (MESA) during the study's baseline visit (2000-2002). Low liver
      attenuation was defined as the lowest quartile and high pericardial adipose
      tissue as the upper quartile of volume (cm(3)). We used standard clinical
      definitions for obesity and abdominal obesity. Insulin resistance was assessed by
      the homeostasis model assessment of insulin resistance (HOMA(IR)) index. In
      multivariate linear regression with all adiposity measures in the model
      simultaneously, all adiposity measures were significantly (P < 0.0001) associated
      with insulin resistance: regression coefficients (+/-s.e.) were 0.31 (+/-0.02)
      for low liver attenuation, 0.27 (+/-0.02) for high pericardial adipose tissue,
      0.27 (+/-0.02) for obesity, and 0.32 (+/-0.02) for abdominal obesity. We found
      significant differences (P = 0.003) between standardized liver attenuation and
      insulin resistance by ethnicity: regression coefficients per 1 s.d. increment
      were 0.10 +/- 0.01 for whites, 0.11 +/- 0.02 for Chinese, 0.08 +/- 0.2 for
      blacks, and 0.14 +/- 0.01 for Hispanics. Liver attenuation and pericardial
      adipose tissue were associated with insulin resistance, independent of BMI and
      waist circumference.

PMID- 21720431
TI  - Weight perceptions among overweight and obese women: a US-Mexico binational
      perspective.
AB  - We examined actual and perceived weight in nationally representative cohorts of
      adults in Mexico (n = 9,527) and the United States (n = 855) using data from the
      National Health and Nutrition Examination Survey (waves 2001-2006) and Mexican
      National Health and Nutrition Survey (2006). Actual weight was assessed by health
      technicians using BMI and perceived weight was collected through self-report. The
      prevalence of overweight or obesity (OO) in Mexican women was 72% and in Mexican
      American women was 71%. OO Mexican-American women were more likely than OO
      Mexican women to label themselves as "overweight" (86% vs. 64%, P < 0.001), and
      this difference was significant while controlling for socio-demographic and
      weight-related variables. Among OO women from both populations, those who had
      been told by a health provider that they were OO were much more likely to
      perceive themselves as such (odds ratio = 5.3; 95% confidence intervals: 3.8
      7.3). Significantly fewer OO women in Mexico than in the United States (13% vs.
      42%, P < 0.0001) recalled having been screened for obesity by their health care
      provider. Weight misperceptions were common in both populations but more
      prevalent in Mexico, and low screening by health providers may be an important
      contributor to poor weight control in both countries.

PMID- 21720432
TI  - Factors predicting nongenetic variability in body weight gain induced by a high
      fat diet in inbred C57BL/6J mice.
AB  - Inbred C57BL/6J mice displayed large individual variations in weight gain when
      fed a high-fat diet (HFD). The objective of this study was to examine whether
      this predominantly nongenetic variability could be predicted by relevant baseline
      features and to explore whether variations in these significant features were
      influenced during pregnancy and/or lactation. Fat mass (FM), fat-free mass (FFM),
      food intake (FI), resting metabolic rate (RMR), physical activity (PA), and body
      temperature (T(b)) were all evaluated at baseline in 60 mice (aged 10-12 weeks)
      before HFD feeding. Regression analyses showed that baseline FM was a strong
      positive predictor of weight gain between 4 and 16 weeks of HFD. Baseline PA was
      negatively associated with weight gain at week 8, 12, and 16, and baseline FFM
      had a positive effect at week 12 and 16. In a second experiment, 40 female mice
      were mated and litter sizes (LS) were manipulated on day 3 of lactation. Weaning
      weight and postweaning growth rate (GR) had positive impacts on FM and FFM at age
      9 weeks (FM, P = 0.001; FFM, P < 0.001: n = 97). Lactation LS had a negative
      effect on weaning weight and a positive effect on postweaning GR. In conclusion,
      our results show that obesity induced by HFD was associated with a higher
      baseline FM, a higher baseline FFM and a lower baseline PA level before the
      exposure of HFD. Two of these traits (FM and FFM) were influenced by lactation LS
      via weaning weight and postweaning GR.

PMID- 21720433
TI  - Intraperitoneal fat is associated with thickening of the thoracic aorta in
      individuals at high risk for cardiovascular events.
AB  - Increased intraperitoneal (IP) fat is associated with increased cardiovascular
      (CV) risk, but mechanisms for this increase in risk are not completely
      established. We performed this study to assess whether IP fat is associated with
      ascending aortic wall thickness (AOWT), a risk factor for CV events. Four hundred
      and forty-one consecutive participants, aged 55-85 years, with risk factors for
      CV events underwent magnetic resonance measures of AOWT and abdominal fat
      (subcutaneous (SC) fat + IP fat). For the ascending aorta, mean wall thickness of
      the 4th quartile of the IP fat was higher relative to the 1st quartile (P <=
      0.001). This difference persisted after accounting for SC fat (P <= 0.001), as
      well as age, gender, height, weight, smoking, diabetes, hypertension, low-density
      lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C),
      and C-reactive protein (CRP) (P < 0.03). Elevated IP fat volume is associated
      with an increase in ascending AOWT, a condition that promotes CV events in middle
      aged and elderly adults.

PMID- 21720434
TI  - Hepatic mitochondrial energetics during catch-up fat with high-fat diets rich in
      lard or safflower oil.
AB  - We have investigated whether altered hepatic mitochondrial energetics could
      explain the differential effects of high-fat diets with low or high omega6
      polyunsaturated fatty acid content (lard vs. safflower oil) on the efficiency of
      body fat recovery (catch-up fat) during refeeding after caloric restriction.
      After 2 weeks of caloric restriction, rats were isocalorically refed with a low
      fat diet (LF) or high-fat diets made from either lard or safflower oil for 1
      week, and energy balance and body composition changes were assessed. Hepatic
      mitochondrial energetics were determined from measurements of liver mitochondrial
      mass, respiratory capacities, and proton leak. Compared to rats refed the LF, the
      groups refed high-fat diets showed lower energy expenditure and increased
      efficiency of fat gain; these differences were less marked with high-safflower
      oil than with high-lard diet. The increase in efficiency of catch-up fat by the
      high-fat diets could not be attributed to differences in liver mitochondrial
      activity. By contrast, the lower fat gain with high-safflower oil than with high
      lard diet is accompanied by higher mitochondrial proton leak and increased
      proportion of arachidonic acid in mitochondrial membranes. In conclusion, the
      higher efficiency for catch-up fat on high-lard diet than on LF cannot be
      explained by altered hepatic mitochondrial energetics. By contrast, the ability
      of the high-safflower oil diet to produce a less pronounced increase in the
      efficiency of catch-up fat may partly reside in increased incorporation of
      arachidonic acid in hepatic mitochondrial membranes, leading to enhanced proton
      leak and mitochondrial uncoupling.

PMID- 21720435
TI  - Impact of high-fat diet and obesity on energy balance and fuel utilization during
      the metabolic challenge of lactation.
AB  - The effects of obesity and a high-fat (HF) diet on whole body and tissue-specific
      metabolism of lactating dams and their offspring were examined in C57/B6 mice.
      Female mice were fed low-fat (LF) or HF diets before and throughout pregnancy and
      lactation. HF-fed mice were segregated into lean (HF-Ln) and obese (HF-Ob) groups
      before pregnancy by their weight gain response. Compared to LF-Ln dams, HF-Ln,
      and HF-Ob dams exhibited a greater positive energy balance (EB) and increased
      dietary fat retention in peripheral tissues (P < 0.05). HF-Ob dams had greater
      dietary fat retention in liver and adipose compared to HF-Ln dams (P < 0.05). De
      novo synthesized fat was decreased in tissues and milk from HF-fed dams compared
      to LF-Ln dams (P < 0.05). However, less dietary and de novo synthesized fat was
      found in the HF-Ob mammary glands compared to HF-Ln (P < 0.05). Obesity was
      associated with reduced milk triglycerides relative to lean controls (P < 0.05).
      Compared to HF diet alone obesity has additional adverse affects, impairing both
      lipid metabolism as well as milk fat production. Growth rates of LF-Ln litters
      were lower than HF-Ln and HF-Ob litters (P < 0.05). Total energy expenditure
      (TEE) of HF-Ob litters was reduced relative to HF-Ln litters, whereas their
      respiratory exchange ratios (RERs) were increased (P < 0.05). Collectively these
      data show that consumption of a HF diet significantly affects maternal and
      neonatal metabolism and that maternal obesity can independently alter these
      responses.

PMID- 21720436
TI  - Breastfeeding and subsequent maternal visceral adiposity.
AB  - Women gain visceral fat during pregnancy. Studies examining the impact of
      breastfeeding on maternal body composition are inconclusive. We examined the
      extent to which breastfeeding was associated with visceral adiposity in a sample
      of US women. This was a cross-sectional analysis of 351 women aged 45-58 years,
      who were free of clinical cardiovascular disease and had not used oral
      contraceptives or hormone replacement therapy in the 3 months prior to enrollment
      in the Study of Women's Health Across the Nation (SWAN)-Heart Study (2001-2003).
      History of breastfeeding was self-reported. Computed tomography was used to
      assess abdominal adiposity. Among premenopausal/early-peri-menopausal mothers,
      those who never breastfed had 28% greater visceral adiposity (95% confidence
      interval (CI): 11-49, P = 0.001), 4.7% greater waist-hip ratio (95% CI: 1.9-7.4,
      P < 0.001), and 6.49 cm greater waist circumference (95% CI: 3.71-9.26, P <
      0.001) than mothers who breastfed all of their children for >=3 months in models
      adjusting for study site; age; parity; years since last birth; socioeconomic,
      lifestyle, and family history variables; early adult BMI; and current BMI. In
      comparison to women who were nulliparous, mothers who breastfed all of their
      children for >=3 months had similar amounts of visceral fat (P > 0.05). In
      contrast, premenopausal/early-peri-menopausal mothers who had never breastfed had
      significantly greater visceral adiposity (42% (95% CI: 17-70), P < 0.001), waist
      circumference (6.15 cm (95% CI: 2.75-9.56), P < 0.001), and waist-hip ratio (3.7%
      (95% CI: 0.69-6.8), P = 0.02) than nulliparous women. No significant
      relationships were observed among late peri-menopausal/postmenopausal women. In
      conclusion, until menopause, mothers who did not breastfeed all of their children
      for >=3 months exhibit significantly greater amounts of metabolically active
      visceral fat than mothers who had breastfed all of their children for >=3 months.

PMID- 21720437
TI  - Early myocardial deformation changes associated to isolated obesity: a study
      based on 3D-wall motion tracking analysis.
AB  - Obesity is considered as a strong risk factor for cardiovascular morbidity and
      mortality. 3D-wall motion tracking echocardiography (3D-WMT) provides information
      regarding different parameters of left ventricular (LV) myocardial deformation.
      Our aim was to assess the presence of early myocardial deformation abnormalities
      in nonselected obese children free from other cardiovascular risk factors. Thirty
      consecutive nonselected obese children and 42 healthy volunteer children were
      enrolled. None of them had any cardiovascular risk factor. Every subject
      underwent a 2D-echo examination and a 3D-WMT study. Mean age was 13.9 +/- 2.56
      and 13.25 +/- 2.68 years in the nonobese and obese groups, respectively (59.7%
      and 40.3% male). Statistically significant differences were found for:
      interventricular septum thickness, LV posterior wall thickness, LV end-diastolic
      volume, LV end-systolic volume, left atrium volume, LV mass, and lateral annulus
      peak velocity. Regarding the results obtained by 3D-WMT assessment, all the
      evaluated parameters were statistically significantly different between the two
      groups. When the influence of obesity on the different echocardiographic
      variables was evaluated by means of multivariate logistic regression analysis,
      the strongest relationship with obesity was found for LV average circumferential
      strain (beta-coefficient: 0.74; r(2): 0.55; P: 0.003). Thus, obesity
      cardiomyopathy is associated not only with structural cardiac changes, but also
      with myocardial deformation changes. Furthermore, this association occurs as
      early as in the childhood and it is independent from any other cardiovascular
      risk factor. The most related parameter to obesity is LV circumferential strain.

PMID- 21720438
TI  - Weight loss and improved gross motor coordination in children as a result of
      multidisciplinary residential obesity treatment.
AB  - This study evaluated the short-term effectiveness of a multidisciplinary
      residential obesity treatment program by describing changes in body weight,
      related measures, and gross motor co-ordination. Secondarily, it was examined to
      what extent the amount of relative weight loss achieved by overweight and obese
      (OW/OB) participants explained the projected improvement in gross motor co
      ordination. Thirty-six OW/OB children (aged 10.5 +/- 1.4 years, 12 girls and 24
      boys) were recruited at the Zeepreventorium VZW (De Haan, Belgium), where they
      followed a specific program consisting of moderate dietary restriction,
      psychological support, and physical activity. For reference purposes, an
      additional group of 36 age- and gender-matched healthy-weight (HW) children was
      included in the study. Anthropometric measures were recorded and gross motor co
      ordination was assessed using the Korperkoordinationstest fur Kinder (KTK) on two
      occasions with an interval of 4 months. Regardless of the test moment, OW/OB
      participants displayed significantly poorer KTK performances (P < 0.001).
      However, treatment was found to be efficacious in decreasing body weight (Delta
      17.9 +/- 3.1%, P < 0.001) and generating a significant progress in gross motor co
      ordination performance, with a greater increase in KTK score(s) from baseline to
      re-test as compared to HW peers (P < 0.01). Within the OW/OB group, the amount of
      relative weight loss explained 26.9% of the variance in improvement in overall
      KTK performance. Therefore, multidisciplinary residential treatment and
      concomitant weight loss can be considered an important means to upgrade OW/OB
      children's level of gross motor co-ordination, which in turn may promote physical
      activity participation.

PMID- 21720439
TI  - Six-minute walk test improved forearm skin blood flow in Tunisian obese women.
AB  - The purpose of this study was to investigate whether 6-min walk test (6MWT) would
      improve the forearm skin blood flow (FSBF) response to acetylcholine (ACh), an
      endothelium-dependent vasodilator, in Tunisian women over a wide range of BMI.
      The FSBF was measured noninvasively using a laser Doppler flowmeter in response
      to local infusion of a cumulative dose of ACh, before and after the 6MWT for 102
      healthy women; the results were expressed as percentage of baseline. The 6MWT was
      monitored and recorded. The mean response of FSBF to ACh was significantly
      greater before as well as after the 6MWT in lean (1,235 +/- 123% vs. 1,644 +/-
      140%) than in overweight (630 +/- 62% vs. 1,080 +/- 66%) and obese subjects (402
      +/- 38% vs. 795 +/- 40%) (P < 0.0001). Our regression analysis also revealed that
      the maximal FSBF response to ACh (i.e., its efficacy) was inversely correlated
      with BMI both before as well as after the 6MWT (r = -0.828, P < 0.0001; r = 
      0.859, P < 0.0001, respectively), and the efficacies of ACh in the three groups
      were all significantly elevated following the 6MWT (P < 0.0001). As indicated by
      ANOVA test, the 6MWT improved the FSBF responses of the lean, overweight, and
      obese subjects, by 33, 71, and 98%, respectively. We confirm that obesity induced
      a reduction of skin vasodilatory reserve and altered both endothelial-dependent
      relaxation and wall compliance. However, our new data clearly demonstrated that
      the 6MWT not only improved significantly the FSBF responses in the three groups
      of women, but the obese patients appeared to benefit more from the 6MWT than the
      overweight and the lean subjects.

PMID- 21720440
TI  - The effect of tesofensine on appetite sensations.
AB  - Tesofensine (TE), an inhibitor of monoamine presynaptic reuptake, has produced
      twice the weight loss seen with currently marketed drugs. However, its long term
      effect on appetite in humans has not been studied. A multicentre phase II trial
      was divided into two parts (24 weeks each). Part 1 had a randomized, double
      blind, placebo-controlled design and Part 2, an open-labeled, single-group,
      uncontrolled design. A drug-free period (12 +/- 3 weeks) separated them. In Part
      1, participants (n = 158) were assigned to 0.25, 0.5 or 1.0 mg TE, or placebo.
      Completers of Part 1 were invited to participate in Part 2 (n = 113), during
      which they all received 0.5 or 1.0 mg TE. Appetite sensations and a composite
      satiety score (CSS = satiety + fullness + (100 - hunger) + (100 - prospective
      food consumption) were assessed. In Part 1 TE induced a dose-dependent increase
      in CSS at week 12 that correlated with weight loss during the 24 weeks (r = 0.36,
      P < 0.0001). However, CSS diminished over time as weight loss progressed (e.g.,
      for 1.0 mg; 52 +/- 17 mm; 64 +/- 13 mm; 55 +/- 13 mm at baseline, week 12 and
      week 24, respectively). After drug withdrawal CSS returned to baseline values (50
      +/- 17 mm, in the whole sample.), despite the participants' reduced-weight state
      (-7.2 +/- 6.7 kg, P < 0.0001). The reintroduction of TE in Part 2 increased CSS
      again (56 +/- 17 mm at week 60), regardless of initial treatment/weight loss. We
      postulate that enhanced satiety is involved in early weight loss. Whether the
      attenuated effect on appetite seen after 24 weeks is due to a counteracting
      effect in the weight reduced state or whether the appetite suppressing effect of
      TE per se diminishes over time is, however, still unclear.

PMID- 21720441
TI  - Beverage vs. solid fruits and vegetables: effects on energy intake and body
      weight.
AB  - Beverage consumption has been implicated in weight gain, but questions remain
      about the veracity of the association, whether the relationship is causal and
      what property of beverages is responsible. It was hypothesized that food form is
      the most salient attribute. Thus, a randomized controlled trial of food form was
      conducted. Energy-matched beverage or solid forms of fruits and vegetables were
      provided to 34, lean or overweight/obese adults for two 8-week periods with a 3
      week washout interspersed. Dietary compensation was incomplete (beverage 53%;
      solid 78%) and body weight increased after the beverage (1.95 +/- 0.33 kg) (77%
      fat mass) and solid (1.36 +/- 0.30 kg) (85% fat mass) treatments (both P <
      0.0005). Differences between food forms were not significant. The lean group had
      the highest dietary compensation (119%) and no significant weight change (0.84 +/
      0.53 kg) after consuming the solid fruits and vegetables whereas the
      overweight/obese group had lower compensation and significant weight gain during
      the solid arm (46%, 1.77 +/- 0.32 kg, P < 0.0001). In contrast, incomplete
      dietary compensation and weight gain occurred in both the lean (43%, 1.61 +/-
      0.44 kg, P = 0.003) and overweight/obese (61%, 2.22 +/- 0.47 kg, P < 0.0005)
      groups during the beverage arm. Secondary analyses revealed the obese group
      gained more weight than the lean and overweight groups during the beverage
      intervention (P = 0.024). These data demonstrate energy consumed as beverages may
      be especially problematic for weight gain. They also indicate that advice to
      increase fruit and vegetable consumption should emphasize total energy intake
      because the additional energy contributed may promote weight gain, especially
      among overweight and obese individuals.

PMID- 21720442
TI  - Obesity reduction within a generation: the dual roles of prevention and
      treatment.
AB  - In 2010, the White House Task Force on Childhood Obesity provided benchmark goals
      for reducing childhood obesity. We evaluated the balance of prevention and
      treatment required for achieving Task Force goals in benchmark years 2015, 2020,
      and 2030. We created a simulation of US birth cohorts (2-19 years) born 2008
      2030. For each year, we assumed "old" birth cohorts (part of previous benchmark
      obesity estimates) would benefit from obesity treatment strategies, and "new"
      birth cohorts would benefit from obesity prevention strategies. We assessed
      obesity prevalence that must be achieved through prevention strategies, under
      varying assumptions of treatment effectiveness. When we assumed a 1% absolute
      reduction in prevalence through treatment, we found that prevention strategies
      would need to achieve an obesity prevalence of 12% by 2015, 8% by 2020, and 0.3%
      by 2030. Because of higher obesity prevalence among minority children, prevention
      strategies would need to achieve a negative prevalence by 2030, which is
      implausible. Under more generous assumptions of treatment effectiveness,
      estimates became positive but remained low. Task Force goals are more difficult
      to achieve with each benchmark year. Policies must focus on obesity treatment
      interventions, particularly targeted to racial/ethnic minority children, to make
      progress in stemming the epidemic.

PMID- 21720443
TI  - Television viewing and obesity in 300 women: evaluation of the pathways of energy
      intake and physical activity.
AB  - We assessed the roles of energy intake and physical activity in the relationships
      among television (TV) viewing, body composition, and obesity using high-quality
      measurement methods. Adult women (n = 300) reported TV viewing behavior, which
      was categorized into infrequent (<= 1 h/day), moderate (2 h/day), and frequent
      (>= 3 h/day) viewing. Body fat percentage (BF%) was assessed using
      plethysmography (Bod Pod) and BMI was calculated from height and body weight.
      Energy intake and physical activity, including time spent in sedentary, moderate,
      and vigorous physical activity (PA), were objectively measured using 7-day
      weighed food records and 7-day accelerometry, respectively. The mean BF% of
      frequent TV viewers (34.6 +/- 6.9%) was significantly greater (F = 3.9, P =
      0.0218) than those of moderate (31.5 +/- 6.7%) and infrequent viewers (30.8 +/-
      7.0%); however, BMI did not differ across the TV viewing groups (F = 0.8, P =
      0.4172). Controlling statistically for differences in age, education, time in
      sedentary activity, time in moderate activity, and energy intake, considered
      individually, had no influence on the relationships between TV viewing and BF%,
      nor TV and BMI. Moreover, the relationship between TV and BF% remained
      significant after adjusting for differences in BMI (F = 3.6, P = 0.0276).
      However, adjusting for total PA reduced the relationship between TV and BF% to
      nonsignificance (F = 2.5, P = 0.0810), as did time spent in vigorous PA (F = 2.2,
      P = 0.1307). These data suggest a strong relationship between TV viewing and BF%.
      This association appears to be due, in part, to differences in total PA,
      particularly vigorous PA, but not time spent in sedentary activity, moderate
      activity, or energy intake.

PMID- 21720444
TI  - Common variants in FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 show evidence of
      association with adult obesity in the Greek population.
AB  - Twenty-four single-nucleotide polymorphisms (SNPs) have been reproducibly
      associated with obesity. We performed a follow-up study for obesity in the Greek
      adult population. A total of 510 obese and 469 lean adults were genotyped for 24
      SNPs. We tested the association with obesity status using logistic regression and
      we evaluated the combined genetic risk of 24 SNPs by calculating the area under
      the receiver-operating characteristic (ROC) curves. We nominally replicated the
      association with obesity (BMI >=30 kg/m(2)) of six SNPs in or near the FTO, MC4R,
      TMEM18, PRL, AIF1, and PCSK1 loci (1.28 <= odds ratio (OR) <= 1.35; 0.004 <= P <=
      0.043). The discrimination ability for obesity was slightly stronger (P = 9.59 *
      10(-6)) when the genetic information of the 24 SNPs was added to nongenetic risk
      factors (area under the curve (AUC) = 0.722) in comparison with nongenetic
      factors analyzed alone (AUC = 0.685). Our data suggest that SNPs in or near the
      FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 loci contribute to obesity risk in the
      Greek population.

PMID- 21720445
TI  - 'The molecular biology of the hamburger'.

PMID- 21720446
TI  - Treasure our rarities.

PMID- 21720447
TI  - Metaclocks.

PMID- 21720448
TI  - Theoretically European, practically overseas.

PMID- 21720449
TI  - New optics sheds light on biology. Advances in microscopy, genetics and
      biochemistry are together increasingly enabling scientists to watch molecules in
      action.

PMID- 21720450
TI  - Tests of homoscedasticity, normality, and missing completely at random for
      incomplete multivariate data.
AB  - Test of homogeneity of covariances (or homoscedasticity) among several groups has
      many applications in statistical analysis. In the context of incomplete data
      analysis, tests of homoscedasticity among groups of cases with identical missing
      data patterns have been proposed to test whether data are missing completely at
      random (MCAR). These tests of MCAR require large sample sizes n and/or large
      group sample sizes n(i), and they usually fail when applied to non-normal data.
      Hawkins (1981) proposed a test of multivariate normality and homoscedasticity
      that is an exact test for complete data when n(i) are small. This paper proposes
      a modification of this test for complete data to improve its performance, and
      extends its application to test of homoscedasticity and MCAR when data are
      multivariate normal and incomplete. Moreover, it is shown that the statistic used
      in the Hawkins test in conjunction with a nonparametric k-sample test can be used
      to obtain a nonparametric test of homoscedasticity that works well for both
      normal and non-normal data. It is explained how a combination of the proposed
      normal-theory Hawkins test and the nonparametric test can be employed to test for
      homoscedasticity, MCAR, and multivariate normality. Simulation studies show that
      the newly proposed tests generally outperform their existing competitors in terms
      of Type I error rejection rates. Also, a power study of the proposed tests
      indicates good power. The proposed methods use appropriate missing data
      imputations to impute missing data. Methods of multiple imputation are described
      and one of the methods is employed to confirm the result of our single imputation
      methods. Examples are provided where multiple imputation enables one to identify
      a group or groups whose covariance matrices differ from the majority of other
      groups.

PMID- 21720451
TI  - Piezoelectric films for high frequency ultrasonic transducers in biomedical
      applications.
AB  - Piezoelectric films have recently attracted considerable attention in the
      development of various sensor and actuator devices such as nonvolatile memories,
      tunable microwave circuits and ultrasound transducers. In this paper, an overview
      of the state of art in piezoelectric films for high frequency transducer
      applications is presented. Firstly, the basic principles of piezoelectric
      materials and design considerations for ultrasound transducers will be
      introduced. Following the review, the current status of the piezoelectric films
      and recent progress in the development of high frequency ultrasonic transducers
      will be discussed. Then details for preparation and structure of the materials
      derived from piezoelectric thick film technologies will be described. Both
      chemical and physical methods are included in the discussion, namely, the sol-gel
      approach, aerosol technology and hydrothermal method. The electric and
      piezoelectric properties of the piezoelectric films, which are very important for
      transducer applications, such as permittivity and electromechanical coupling
      factor, are also addressed. Finally, the recent developments in the high
      frequency transducers and arrays with piezoelectric ZnO and PZT thick film using
      MEMS technology are presented. In addition, current problems and further
      direction of the piezoelectric films for very high frequency ultrasound
      application (up to GHz) are also discussed.

PMID- 21720452
TI  - Violence Breeds Violence: Childhood Exposure and Adolescent Conduct Problems.
AB  - The relationships between childhood exposure to violence and adolescent conduct
      problems were investigated in a sample of 88 primiparous adolescent mothers and
      their children. Regression analyses revealed that witnessing violence and
      victimization prior to age 10 predicted delinquency and violent behaviors, even
      after controlling for prenatal maternal and early childhood externalizing
      problems. Social competency and depression during middle childhood moderated the
      relationship between victimization and violent behaviors for girls, but not boys:
      Lower levels of social competency and depression served as risk factors for
      delinquency among teenage girls who experienced victimization during childhood.
      These findings have important implications for youth violence prevention
      programs.

PMID- 21720453
TI  - Are Some Negotiators Better Than Others? Individual Differences in Bargaining
      Outcomes.
AB  - The authors address the long-standing mystery of stable individual differences in
      negotiation performance, on which intuition and conventional wisdom have clashed
      with inconsistent empirical findings. The present study used the Social Relations
      Model to examine individual differences directly via consistency in performance
      across multiple negotiations and to disentangle the roles of both parties within
      these inherently dyadic interactions. Individual differences explained a
      substantial 46% of objective performance and 19% of subjective performance in a
      mixed-motive bargaining exercise. Previous work may have understated the
      influence of individual differences because conventional research designs require
      specific traits to be identified and measured. Exploratory analyses of a battery
      of traits revealed few reliable associations with consistent individual
      differences in objective performance-except for positive beliefs about
      negotiation, positive affect, and concern for one's outcome, each of which
      predicted better performance. Findings suggest that the field has large untapped
      potential to explain substantial individual differences. Limitations, areas for
      future research, and practical implications are discussed.

PMID- 21720454
TI  - A consistent local linear estimator of the covariate adjusted correlation
      coefficient.
AB  - Consider the correlation between two random variables (X, Y), both not directly
      observed. One only observes X = phi(1)(U)X + phi(2)(U) and Y = psi(1)(U)Y +
      psi(2)(U), where all four functions {phi(l)(.),psi(l)(.), l = 1, 2} are
      unknown/unspecified smooth functions of an observable covariate U. We consider
      consistent estimation of the correlation between the unobserved variables X and
      Y, adjusted for the above general dual additive and multiplicative effects of U,
      based on the observed data (X, Y, U).

PMID- 21720455
TI  - Charm or Harm: Effect of Passage Content on Listener Attitudes toward American
      English Accents.
AB  - This study examined how passage content influences attitudes towards American
      English Accents. Participants listened to passages differing in topic content
      spoken in an American Southern English or Standard American English accent.
      Although Southern-accented speakers were rated higher in sociality, but lower in
      status, than standard-accented speakers, sociality ratings varied as a function
      of passage topic only for Standard-accented speakers. Linguistic content appeared
      most likely to influence listeners' attitudes when preexisting assumptions based
      on regional accent were absent.

PMID- 21720456
TI  - A dosing study of bone marrow mononuclear cells for transendocardial injection in
      a pig model of chronic ischemic heart disease.
AB  - We studied the effect of the dose of bone marrow mononuclear cells, delivered via
      transendocardial injection, upon capillary density and fibrosis in pigs with
      chronic ischemic heart disease.Pigs (n = 16) that had undergone ameroid
      constrictor placement (left circumflex coronary artery) to induce chronic
      ischemia were divided equally into 4 groups on the basis of bone marrow
      mononuclear cell dose: control (saline injection) and 50, 100, or 200 * 10(6)
      bone marrow mononuclear cells. Thirty days after ameroid placement, each pig
      received 13 transendocardial NOGA-guided injections. An implantable loop recorder
      monitored possible arrhythmias caused by cell transplantation. Thirty days later,
      the pigs were killed, and their hearts were evaluated histopathologically for
      fibrosis and capillary density; the number of cells per segment was correlated
      with fibrosis and capillary density. No adverse events, arrhythmias, or cardiac
      inflammatory reactions were associated with cell therapy. Less fibrosis was seen
      in pigs that received 100 * 10(6) cells than in control pigs. A trend toward
      higher capillary density was seen with higher cell concentrations. Segments
      injected with more than 20 * 10(6) million cells had the highest capillary
      density and the least amount of fibrosis (P < 0.05 vs controls).In conclusion,
      transendocardial injections (up to 200 * 10(6) bone marrow mononuclear cells)
      were safe. Analyses of individual injected segments suggest potential benefit
      from higher cell concentrations per segment.

PMID- 21720457
TI  - Embolic risk in atrial fibrillation that arises from hyperthyroidism: review of
      the medical literature.
AB  - Atrial fibrillation, the most common cardiac complication of hyperthyroidism,
      occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The
      prevalence of atrial fibrillation increases with age in the general population
      and in thyrotoxic patients. Other risk factors for atrial fibrillation in
      thyrotoxic patients include male sex, ischemic or valvular heart disease, and
      congestive heart failure. The incidence of arterial embolism or stroke in
      thyrotoxic atrial fibrillation is less clear. There are many reports of arterial
      thromboembolism associated with hyperthyroidism, including cases of young adults
      without coexisting risk factors other than thyrotoxic atrial fibrillation. The
      use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic
      atrial fibrillation is controversial: National organizations provide conflicting
      recommendations in their practice guidelines. Herein, we review the medical
      literature and examine the evidence behind the recommendations in order to
      determine the best approach to thromboembolic prophylaxis in patients who have
      atrial fibrillation that is associated with hyperthyroidism.

PMID- 21720458
TI  - Rosuvastatin therapy does not affect serum MMP-13 or TIMP-1 levels in
      hypercholesterolemic patients.
AB  - Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque
      and reduce plaque stability. In tissue sections of atherosclerotic plaque, the
      expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors (statins) decrease the tissue expression of
      matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating
      the inflammatory process that leads to increased expression. However, it is not
      known whether statins decrease levels of matrix metalloproteinase-13--an enzyme
      crucial to the initiation of collagen degradation-as part of their plaque
      stabilizing effect.We prospectively examined the effect of statin therapy on
      serum levels of matrix metalloproteinase-13, tissue inhibitor of
      metalloproteinase-1, and low-density-lipoprotein cholesterol in 14 patients with
      hypercholesterolemia. All were at low risk for adverse cardiovascular events and
      were given 20 mg/d of rosuvastatin for 4 weeks. Post-therapy levels of matrix
      metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were compared
      with baseline levels. Although low-density-lipoprotein cholesterol levels were
      significantly decreased in the 14 patients (mean baseline level, 152 +/- 21 mg/dL
      vs mean post-therapy level, 73 +/- 45 mg/dL; P < 0.001), matrix metalloproteinase
      13 and tissue inhibitor of metalloproteinase-1 levels were unchanged (matrix
      metalloproteinase-13, 0.295 +/- 0.06 ng/mL vs 0.323 +/- 0.11 ng/mL, P = 0.12; and
      tissue inhibitor of metalloproteinase-1, 400.8 +/- 43.4 ng/mL vs 395.3 +/- 47.5
      ng/mL, P = 0.26). We conclude that even though there was a decrease in low
      density-lipoprotein cholesterol, short-term, high-dose rosuvastatin therapy has
      no effect on matrix metalloproteinase-13 and tissue inhibitor of
      metalloproteinase-1 levels in hypercholesterolemic patients. However, further
      investigation is warranted.

PMID- 21720459
TI  - Left ventricular function improves after pulmonary valve replacement in patients
      with previous right ventricular outflow tract reconstruction and biventricular
      dysfunction.
AB  - Congenital heart defects that have a component of right ventricular outflow tract
      obstruction, such as tetralogy of Fallot, are frequently palliated in childhood
      by disruption of the pulmonary valve. Although this can provide an initial
      improvement in quality of life, these patients are often left with severe
      pulmonary valve insufficiency. Over time, this insufficiency can lead to
      enlargement of the right ventricle and to the deterioration of right ventricular
      systolic and diastolic function. Pulmonary valve replacement in these patients
      decreases right ventricular volume overload and improves right ventricular
      performance. To date, few studies have examined the effects of pulmonary valve
      replacement on left ventricular function in patients with biventricular
      dysfunction. We sought to perform such an evaluation.Records of adult patients
      who had undergone pulmonary valve replacement from January 2003 through November
      2006 were analyzed retrospectively. We reviewed preoperative and postoperative
      echocardiograms and calculated left ventricular function in 38 patients.In the
      entire cohort, the mean left ventricular ejection fraction increased by a mean of
      0.07 after pulmonary valve replacement, which was a statistically significant
      change (P < 0.01). In patients with preoperative ejection fractions of less than
      0.50, mean ejection fractions increased by 0.10.We conclude that pulmonary valve
      replacement in patients with biventricular dysfunction arising from severe
      pulmonary insufficiency and right ventricular enlargement can improve left
      ventricular function. Prospective studies are needed to verify this finding.

PMID- 21720460
TI  - Sildenafil therapy for pulmonary hypertension before and after pediatric
      congenital heart surgery.
AB  - Pulmonary hypertension associated with pediatric congenital heart defects is a
      major cause of postoperative morbidity and death. Sildenafil has been combined
      with inhaled nitric oxide to treat pulmonary hypertension. We retrospectively
      studied the pre- and postoperative effects of oral sildenafil as monotherapy in
      children with pulmonary hypertension who underwent surgery to correct congenital
      cardiac defects. From September 2005 through November 2009, 38 children with
      moderate-to-severe pulmonary arterial hypertension (pulmonary arterial/aortic
      pressure ratio, >0.7) underwent cardiac surgery at our institution. Fifteen
      patients were given sildenafil (0.35 mg/kg, every 4 hr) orally or through
      nasogastric tubes 1 week before and 1 week after surgery. Twenty-three patients
      of comparable medical status were given sildenafil only upon the institution of
      cardiopulmonary bypass and for 1 week after surgery. Postoperatively, the 15
      patients who were given preoperative sildenafil had significantly lower mean
      pulmonary arterial pressures (25.6 +/- 3.1 vs. 30.4 +/- 5.7 mmHg; P = 0.005) and
      pulmonary arterial/aortic pressure ratios (0.35 +/- 0.05 vs. 0.42 +/- 0.07; P =
      0.002) than did the other 23 patients. The preoperative therapy also shortened
      cardiopulmonary bypass time, mechanical ventilation time, and lengths of
      intensive care unit and hospital stays. No sildenafil-related hypertensive crises
      or sequelae occurred. As monotherapy, oral sildenafil in low doses appears to
      control pulmonary hypertension safely and effectively in children undergoing
      operations to correct congenital heart defects, particularly when it is given
      both preoperatively and postoperatively. Further study is warranted.

PMID- 21720461
TI  - Mitral insufficiency due to an isolated anterior-leaflet cleft: correction with
      an autologous pericardial patch supported by artificial chordae.
AB  - Congenital clefts of the mitral valve without an associated atrioventricular
      canal defect are rare, and they may cause mitral insufficiency that requires
      surgical correction. Repair is typically by direct suture; however, if the cleft
      is especially wide, the use of this technique may distort the valve leaflet and
      cause poor coaptation with valvular insufficiency.Herein, we present the case of
      a 39-year-old woman who had severe mitral valve insufficiency secondary to a wide
      isolated cleft of the anterior mitral leaflet. The valve was reconstructed with
      an autologous pericardial patch supported by polytetrafluoroethylene neochordae
      and an implanted annuloplasty ring. Echocardiographic examination 1 year
      postoperatively showed excellent competence of the mitral valve and good
      coaptation of the leaflets. To our knowledge, this is the 1st report that
      describes the use of artificial neochordae to support an autologous pericardial
      patch in the repair of a cleft in the anterior mitral valve leaflet.

PMID- 21720462
TI  - Cardiac dysfunction after cancer treatment.
AB  - Onco-cardiology is an evolving discipline that requires the consideration of
      cardiotoxicity in preclinical, clinical,and therapeutic aspects of protocol
      development,treatment, and surveillance of patients who have undergone
      interventions using cardiotoxic agents. Only then can we foster new ways to
      maximize survival while keeping cardiac damage within acceptable limits. It is to
      this end that our working together has brought us to our present understanding.
      In the future, we may expect onco-cardiology to play an even greater role in the
      care of cancer patients.

PMID- 21720463
TI  - Cardiotoxicity due to cancer therapy.
AB  - The convergence of novel molecular techniques for the study of cardiovascular
      disease-together with the development of an armamentarium of molecular-targeted
      anticancer therapies-is fueling the interest of molecular cardiologists in
      probing the mechanisms of cancer-therapy-induced cardiac toxicity. Such studies
      have the potential to develop strategies that will prevent cardiac toxicity from
      becoming a barrier to effective anticancer therapy. They might also provide novel
      insights into the pathogenesis of non-cancer-therapy-induced human heart disease.

PMID- 21720464
TI  - Risks of heart disease after radiotherapy.

PMID- 21720465
TI  - Cardiovascular interventions in thrombocytopenic cancer patients.

PMID- 21720466
TI  - Primary cardiac tumors.

PMID- 21720467
TI  - Hypertension in cancer patients.

PMID- 21720468
TI  - Managing cardiac risk factors in oncology clinical trials.

PMID- 21720469
TI  - Imaging for cardiotoxicity in cancer patients.

PMID- 21720470
TI  - Going around the bend: deep inspiration facilitates difficult stent delivery in
      the native coronary arteries.
AB  - Percutaneous coronary intervention in tortuous or calcified vessels poses a
      substantial challenge for interventional cardiologists. Many techniques have been
      described to overcome the challenge, including the use of stiffer wires, buddy
      wires, the anchor balloon technique, and deep seating of the guide catheter.
      Herein, we describe a way to facilitate stent delivery in many tortuous,
      calcified, and acutely angled vessels: having the patient take a deep breath
      during the delivery. Deep inspiration displaces the diaphragm and the heart into
      a more vertical position and causes the coronary tree to straighten slightly,
      which facilitates balloon and stent delivery. We have found that this method
      minimizes patients' radiation exposure and saves substantial time and expense in
      many balloon and stent deliveries that would otherwise be challenging.

PMID- 21720471
TI  - Tumor-like coronary atheroma: a modern coronary evaluation with a historical
      perspective.
AB  - The concept that atherosclerotic disease could be a form of neoplasm has been
      proposed in the medical literature for centuries, yet few modern cardiologists or
      pathologists describe atherosclerotic plaques as having the appearance of tumors.
      Although atherosclerosis is now considered to be an inflammatory disease,
      parallels between the pathophysiologic courses of atherosclerosis and neoplasia
      have been described since the 19th century. Current research is increasingly
      focused on mechanisms common to both diseases.Herein, we present the case of a 70
      year-old man with a tumor-like coronary atheroma that was diagnosed on computed
      tomographic coronary angiography and confirmed with the use of intravascular
      ultrasound. However, the large plaque was not apparent on conventional invasive
      angiography. This case serves as a reminder of the limitations of invasive
      angiography and of the superiority of both computed tomographic coronary
      angiography and intravascular ultrasound in identifying and quantifying coronary
      plaque. We discuss our interpretation of the patient's lesion and review various
      theories of atherogenesis.

PMID- 21720472
TI  - Resection of left ventricular fibroma with subacute papillary muscle rupture.
AB  - Cardiac fibroma is a rare, benign tumor that occurs chiefly in children and
      rarely in adults. Most fibromas occur in the ventricles and may reach a very
      large size that complicates surgical removal. Herein, we report the case of a 38
      year-old woman who presented with shortness of breath, fatigue, and
      lightheadedness and was found to have a 6 * 8-cm fibroma of the left ventricle.
      Surgical resection was successful, but 7 days later she developed sudden-onset
      severe mitral regurgitation due to partial disruption of the posterolateral
      papillary muscle. Mitral valve replacement with a 27-mm mechanical valve was
      performed. Five years later, the patient remained well, without evident tumor
      recurrence or cardiac dysfunction.Mitral valve dysfunction with regurgitation has
      been reported to occur before, immediately after, and late after the resection of
      left ventricular fibromas. To our knowledge, this is the 1st report of subacute
      papillary muscle rupture after the resection of a left ventricular fibroma. This
      case highlights the need to evaluate mitral valve function by carefully
      inspecting the resection margins after surgery and interpreting the
      echocardiographic results during the acute, subacute, and late time frames.

PMID- 21720473
TI  - Metastatic carcinoid tumor obstructing left ventricular outflow.
AB  - Cardiac tumors are rare and usually indicate metastatic disease. Characterizing a
      tumor and reaching an exact diagnosis can be difficult. Diagnosis has been aided
      greatly by advances in imaging, such as cardiovascular magnetic resonance with
      the use of gadolinium-pentetic acid. Carcinoid tumors are neuroendocrine
      neoplasms that are found most often in the intestinal tract, although they can
      also develop in the lung, stomach, or heart. Herein, we report the case of a 72
      year-old woman with a history of intestinal carcinoid disease and presenting
      symptoms of dizziness, fatigue, and chest pain. We used cardiovascular magnetic
      resonance with gadolinium enhancement to identify a large mass obstructing left
      ventricular outflow. The histopathologic results of an endomyocardial biopsy
      confirmed that the mass was a left-sided metastatic carcinoid cardiac tumor. To
      our knowledge, we are reporting the 1st combined use of clinical evaluation,
      cardiovascular magnetic resonance, and histopathologic studies to reach such a
      diagnosis.

PMID- 21720474
TI  - Sweet syndrome, cutis laxa, and fatal cardiac manifestations in a 2-year-old
      girl.
AB  - A 2-year-old black girl was diagnosed with Sweet syndrome and cutis laxa, and she
      was given corticosteroid therapy. At that presentation, a cardiac evaluation
      revealed nothing unusual. Nine days later, she emergently presented with
      respiratory distress, and circulatory collapse rapidly developed. A 2-dimensional
      Doppler echocardiogram showed a dilated and poorly contractile left ventricle,
      severe aortic regurgitation, and a large aneurysm of the sinus of Valsalva.
      Despite resuscitative efforts, the child died. Inspection on autopsy revealed a
      markedly enlarged heart and 2 large aneurysms of the sinus of Valsalva.
      Histologic analysis disclosed acute necrosis in the cardiac apex and
      interventricular septum, and focal chronic inflammatory and granulation tissue in
      the aortic wall.Because cardiac lesions may remain clinically silent, we
      recommend that children with Sweet syndrome and cutis laxa undergo complete
      cardiac evaluation, including 2-dimensional Doppler echocardiography, by a
      pediatric cardiologist. Subsequent monitoring is also appropriate. Early
      recognition and aggressive therapeutic treatment could prevent fatal cardiac
      complications.

PMID- 21720475
TI  - Varicella myopericarditis mimicking myocardial infarction in a 17-year-old boy.
AB  - Varicella (chickenpox), a common childhood infection caused by the varicella
      zoster virus, is self-limiting and usually benign. Although atypical
      manifestations of the virus are occasionally seen, it rarely presents with
      cardiovascular sequelae. Cardiovascular complications of varicella can include
      pericarditis, myocarditis, or endocarditis. Herein, we report the case of a 17
      year-old boy who had varicella infection and severe chest pain. Examination
      revealed atypical electrocardiographic findings of pericarditis and remarkably
      elevated cardiac biomarker levels: peak cardiac troponin I, 37.2 ng/mL; total
      creatine kinase, 1,209 U/L; and creatine kinase-MB fraction, 133.6 ng/mL. After
      results of coronary angiography reliably excluded ischemia and myocardial
      infarction, the diagnosis was varicella myopericarditis. The patient was placed
      on a medical regimen during and after 5 days of hospitalization. In 2 weeks, he
      was asymptomatic, and at 6 months, he was doing well and had normal
      electrocardiographic and echocardiographic results.To our knowledge, cardiac
      enzyme elevations to these levels have not been reported in cases of
      cardiovascular sequelae of varicella. We discuss the diagnostic challenges of
      this atypical case and suggest that clinicians be aware that varicella disease is
      most often, but not always, benign.

PMID- 21720476
TI  - Recurrent polymorphic ventricular tachycardia treated by ablation of Purkinje
      arborization within an infarct border-zone.
AB  - A 70-year-old patient with 3-vessel coronary artery disease and a left
      ventricular aneurysm underwent coronary artery bypass grafting, together with a
      surgical anterior ventricular endocardial restoration (SAVER) procedure. Four
      days later, he suddenly developed recurrent sustained and nonsustained
      polymorphic ventricular tachycardia, preceded by monomorphic ventricular
      premature contractions, and did not respond to any antiarrhythmic drug, including
      lidocaine, esmolol, or amiodarone. Repeated electrical cardioversion procedures
      were performed (28 in total). Mapping was performed to target the earliest site
      of activation in the left ventricle during the ventricular premature
      contractions, a site where the premature beats were preceded by Purkinje
      potentials. That site was located along a scar border-zone. Ablation at that site
      resulted in the disappearance of the monomorphic ventricular premature
      contractions and in the complete suppression of the electrical storm. These
      findings appear to indicate that the area in which the Purkinje potentials were
      recorded along the scar border-zone played an important role in the mechanism of
      the polymorphic ventricular tachycardia after myocardial infarction.

PMID- 21720477
TI  - Double-valve Libman-Sacks endocarditis causing ventricular fibrillation cardiac
      arrest.
AB  - Libman-Sacks endocarditis is a well-known and rather common cardiac manifestation
      of systemic lupus erythematosus. Transesophageal and transthoracic
      echocardiography are the definitive imaging methods used to evaluate cardiac
      valvular involvement in this disease. Valvular masses (vegetations) and valvular
      thickening are 2 common morphologic echocardiographic patterns. Libman-Sacks
      lesions are typically characterized by single-valve involvement and their small
      size of 1 to 4 mm.Herein, we present the unusual case of a 22-year-old woman with
      newly diagnosed systemic lupus erythematosus who had large, sterile vegetations
      of Libman-Sacks endocarditis that involved the mitral and aortic valves. This
      compromised coronary blood flow and resulted in ventricular fibrillation cardiac
      arrest. The vegetations were surgically excised, and the patient's cardiac
      function recovered. We discuss the treatment of the patient and that of Libman
      Sacks endocarditis.

PMID- 21720478
TI  - Minimally invasive transaortic mitral valve repair during aortic valve
      replacement.
AB  - Herein, we report the case of a 77-year-old man who presented with congestive
      heart failure. Echocardiography and cardiac catheterization revealed severe
      aortic stenosis with severe mitral regurgitation and a left ventricular ejection
      fraction of 0.20. Because of comorbidities, the patient was considered to be at
      high risk for double-valve surgery. In order to reduce the operative risk, a
      minimally invasive aortic valve replacement was performed together with a
      transaortic edge-to-edge repair (Alfieri stitch) of the mitral valve. We discuss
      the surgical technique and note the positive outcome. To our knowledge, this is
      the 1st report of minimally invasive aortic valve replacement and transaortic
      mitral valve repair with use of the Alfieri stitch.

PMID- 21720479
TI  - Surgical management of double-chambered right ventricle in adults.
AB  - Double-chambered right ventricle is a congenital anomaly in which the right
      ventricle is divided into 2 portions by anomalous muscle bundles. These cases
      often present in children, but rarely in adults. We discuss 2 cases of double
      chambered right ventricle, in patients aged 42 and 35 years. When cases remain
      asymptomatic until adulthood, they can present with unusual symptoms that lead to
      incorrect diagnosis. Our cases represent 2 very different manifestations of
      double-chambered right ventricle, which differ in presentation, in the site of
      abnormal obstructive muscle bundles, and in the presence of associated lesions.
      Both of our patients underwent successful surgical resection of the obstruction.
      One patient also underwent closure of a ventricular septal defect. We also review
      the literature on the various mechanisms that have been proposed to account for
      the complex morphology of the abnormal muscle bundles.

PMID- 21720480
TI  - Tricuspid valve repair for torrential tricuspid regurgitation after permanent
      pacemaker lead extraction.
AB  - Tricuspid regurgitation secondary to percutaneous lead extraction is uncommon,
      and it rarely requires surgical intervention. Most tricuspid regurgitation occurs
      during the implantation of tined leads, which can be entrapped in the tricuspid
      valve apparatus and may require immediate withdrawal. Severe tricuspid
      regurgitation as a sequela of extracting chronically implanted leads has rarely
      been reported. Herein, we report a case of torrential tricuspid regurgitation in
      a 67-year-old woman after the extraction of a permanent pacemaker lead. The
      regurgitation was confirmed on transesophageal echocardiography during lead
      extraction, and the tricuspid valve was successfully repaired with suture
      bicuspidization of the valve and the support of ring annuloplasty. A short review
      of the relevant literature follows the case report.

PMID- 21720481
TI  - Large pulmonary arteriovenous malformation diagnosed by cardiovascular magnetic
      resonance.

PMID- 21720482
TI  - Giant coronary sinus.

PMID- 21720483
TI  - Systolic compression of the septal artery: an unusual angiographic finding.

PMID- 21720484
TI  - Giant right coronary artery and coronary sinus aneurysm due to fistula.

PMID- 21720485
TI  - Giant aneurysm of a saphenous vein graft with shunting into the right atrium.

PMID- 21720486
TI  - Ectatic coronary arteries in Noonan syndrome.

PMID- 21720488
TI  - Primary pulmonary artery sarcoma extending retrograde into the superior vena
      cava.

PMID- 21720489
TI  - Value of cardiac magnetic resonance in diagnosing takotsubo cardiomyopathy.

PMID- 21720491
TI  - Spontaneous pneumopericardium as the first indication of an intrapericardial
      bronchogenic cyst.

PMID- 21720492
TI  - Investigation of the response of microstructures under the combined effect of
      mechanical shock and electrostatic forces.
AB  - There is strong experimental evidence for the existence of strange modes of
      failure of microelectromechanical systems (MEMS) devices under mechanical shock
      and impact. Such failures have not been explained with conventional models of
      MEMS. These failures are characterized by overlaps between moving microstructures
      and stationary electrodes, which cause electrical shorts. This work presents
      modeling and simulation of MEMS devices under the combination of shock loads and
      electrostatic actuation, which sheds light on the influence of these forces on
      the pull-in instability. Our results indicate that the reported strange failures
      can be attributed to early dynamic pull-in instability. The results show that the
      combination of a shock load and an electrostatic actuation makes the instability
      threshold much lower than the threshold predicted, considering the effect of
      shock alone or electrostatic actuation alone. In this work, a single-degree-of
      freedom model is utilized to investigate the effect of the shock-electrostatic
      interaction on the response of MEMS devices. Then, a reduced-order model is used
      to demonstrate the effect of this interaction on MEMS devices employing
      cantilever and clamped-clamped microbeams. The results of the reduced-order model
      are verified by comparing with finite-element predictions. It is shown that the
      shock-electrostatic interaction can be used to design smart MEMS switches
      triggered at a predetermined level of shock and acceleration.

PMID- 21720493
TI  - Characterization for the performance of capacitive switches activated by
      mechanical shock.
AB  - This paper presents experimental and theoretical investigation of a new concept
      of switches (triggers) that are actuated at or beyond a specific level of
      mechanical shock or acceleration. The principle of operation of the switches is
      based on dynamic pull-in instability induced by the combined interaction between
      electrostatic and mechanical shock forces. These switches can be tuned to be
      activated at various shock and acceleration thresholds by adjusting the DC
      voltage bias. Two commercial off-the-shelf capacitive accelerometers operating in
      air are tested under mechanical shock and electrostatic loading. A single-degree
      of-freedom model accounting for squeeze-film damping, electrostatic forces, and
      mechanical shock is utilized for the theoretical investigation. Good agreement is
      found between simulation results and experimental data. Our results indicate that
      designing these new switches to respond quasi-statically to mechanical shock
      makes them robust against variations in shock shape and duration. More
      importantly, quasi-static operation makes the switches insensitive to variations
      in damping conditions. This can be promising to lower the cost of packaging for
      these switches since they can operate in atmospheric pressure with no hermetic
      sealing or costly package required.

PMID- 21720494
TI  - Identification of Novel Phosphorylation Motifs Through an Integrative
      Computational and Experimental Analysis of the Human Phosphoproteome.
AB  - Protein phosphorylation occurs in certain sequence/structural contexts that are
      still incompletely understood. The amino acids surrounding the phosphorylated
      residues are important in determining the binding of the kinase to the protein
      sequence. Upon phosphorylation these sequences also determine the binding of
      certain domains that specifically bind to phosphorylated sequences. Thus far,
      such 'motifs' have been identified through alignment of a limited number of well
      identified kinase substrates. RESULTS: Experimentally determined phosphorylation
      sites from Human Protein Reference Database were used to identify 1,167 novel
      serine/threonine or tyrosine phosphorylation motifs using a computational
      approach. We were able to statistically validate a number of these novel motifs
      based on their enrichment in known phosphopeptides datasets over
      phosphoserine/threonine/tyrosine peptides in the human proteome. There were 299
      novel serine/threonine or tyrosine phosphorylation motifs that were found to be
      statistically significant. Several of the novel motifs that we identified
      computationally have subsequently appeared in large datasets of experimentally
      determined phosphorylation sites since we initiated our analysis. Using a peptide
      microarray platform, we have experimentally evaluated the ability of casein
      kinase I to phosphorylate a subset of the novel motifs discovered in this study.
      Our results demonstrate that it is feasible to identify novel phosphorylation
      motifs through large phosphorylation datasets. Our study also establishes peptide
      microarrays as a novel platform for high throughput kinase assays and for the
      validation of consensus motifs. Finally, this extended catalog of phosphorylation
      motifs should assist in a systematic study of phosphorylation networks in signal
      transduction pathways.

PMID- 21720495
TI  - Coparenting in kinship Families With Incarcerated Mothers: A Qualitative Study.
AB  - The number of incarcerated mothers has risen steadily in the past 20 years, with
      a majority of the mothers' children being cared for by relatives, usually the
      maternal grandmother (Smith, Krisman, Strozier, & Marley, 2004). This article
      examines the unique coparenting relationship of grandmothers and mothers through
      qualitative individual interviews with a sample of 24 incarcerated mothers with
      children between the ages of 2 and 6, and 24 grandmothers raising their children.
      The study revealed many different variants of healthy coparenting alliances,
      achieved against often huge odds. Much variation was also discovered in dyads
      where coparenting alliances were not as successful. Implications for practice
      include performing structural family assessments, enhancing jail education
      programs, and offering extended coparenting treatment after discharge.

PMID- 21720496
TI  - Optimal-Flow Minimum-Cost Correspondence Assignment in Particle Flow Tracking.
AB  - A diversity of tracking problems exists in which cohorts of densely packed
      particles move in an organized fashion, however the stability of individual
      particles within the cohort is low. Moreover, the flows of cohorts can regionally
      overlap. Together, these conditions yield a complex tracking scenario that can
      not be addressed by optical flow techniques that assume piecewise coherent flows,
      or by multiparticle tracking techniques that suffer from the local ambiguity in
      particle assignment. Here, we propose a graph-based assignment of particles in
      three consecutive frames to recover from image sequences the instantaneous
      organized motion of groups of particles, i.e. flows. The algorithm makes no a
      priori assumptions on the fraction of particles participating in organized
      movement, as this number continuously alters with the evolution of the flow
      fields in time. Graph-based assignment methods generally maximize the number of
      acceptable particles assignments between consecutive frames and only then
      minimize the association cost. In dense and unstable particle flow fields this
      approach produces many false positives. The here proposed approach avoids this
      via solution of a multi-objective optimization problem in which the number of
      assignments is maximized while their total association cost is minimized at the
      same time. The method is validated on standard benchmark data for particle
      tracking. In addition, we demonstrate its application to live cell microscopy
      where several large molecular populations with different behaviors are tracked.

PMID- 21720497
TI  - Synthetic cation transporters incorporating crown ethers and calixarenes as
      headgroups and central relays: a comparison of sodium and chloride selectivity.
AB  - An earlier study showed that a calix[4]arene could function as a central relay
      unit to form an ion conductance pathway through a phospholipid bilayer membrane.
      The present study expands the range of compounds from calix[4]arene to
      calix[6]arene and incorporates them either as central units or as headgroups,
      substituting one or more diaza-18-crown-6 residues in functioning hydraphiles.
      Ion release was assayed by detecting either Na(+) or Cl(-) release from
      phospholipid vesicles. The ion transport activity for calix[4]arenes in either
      position is modest, but is almost non-existent when calix[6] residues were
      incorporated either as head groups or central relay units. The poor activity of
      the calix[6]arenes may result from an inability to penetrate to the midplane of
      the bilayer or pass entirely through it to form a conductance pathway. The
      transmembrane "flip-flop" may result from high polarity or steric bulk, or both.
      A hydraphile incorporating a single -NHCOC(6)H(4)OCH(2)CONH- as a central relay
      proved to be an excellent Na(+) conductor, but less selective for Cl(-). The fact
      that this new hydraphile molecule shows selectivity for Na (+) over Cl(-)
      transport and possesses two secondary amide residues in the central relay
      suggests a means to control ion selectivity in synthetic ion transporters.

PMID- 21720498
TI  - Acute and subchronic dermal toxicity of nanosilver in guinea pig.
AB  - Silver has been used as an antimicrobial agent for a long time in different
      forms, but silver nanoparticles (nanosilver) have recently been recognized as
      potent antimicrobial agents. Although nanosilver is finding diverse medical
      applications such as silver-based dressings and silver-coated medical devices,
      its dermal and systemic toxicity via dermal use has not yet been identified. In
      this study, we analyzed the potential toxicity of colloidal nanosilver in acute
      and subchronic guinea pigs. Before toxicity assessments, the size of colloidal
      nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission
      electron microscopy. For toxicological assessments, male guinea pigs weighing 350
      to 400 g were exposed to two different concentrations of nanosilver (1000 and
      10,000 MUg/mL) in an acute study and three concentrations of nanosilver (100,
      1000, and 10,000 MUg/mL) in a subchronic study. Toxic responses were assessed by
      clinical and histopathologic parameters. In all experimental animals the sites of
      exposure were scored for any type of dermal toxicity and compared with negative
      control and positive control groups. In autopsy studies during the acute test, no
      significant changes in organ weight or major macroscopic changes were detected,
      but dose-dependent histopathologic abnormalities were seen in skin, liver, and
      spleen of all test groups. In addition, experimental animals subjected to
      subchronic tests showed greater tissue abnormalities than the subjects of acute
      tests. It seems that colloidal nanosilver has the potential to provide target
      organ toxicities in a dose- and time-dependent manner.

PMID- 21720499
TI  - High-energy ball milling technique for ZnO nanoparticles as antibacterial
      material.
AB  - Nanoparticles of zinc oxide (ZnO) are increasingly recognized for their utility
      in biological applications. In this study, the high-energy ball milling (HEBM)
      technique was used to produce nanoparticles of ZnO from its microcrystalline
      powder. Four samples were ball milled for 2, 10, 20, and 50 hours, respectively.
      The structural and optical modifications induced in the 'as synthesized'
      nanomaterials were determined by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), transmission electron microscope (TEM), and photoluminescence
      emission spectra (PL). SEM and TEM results show a gradual decrease in particle
      size from around 600 to ~30 nm, with increased milling time. The initial
      microstructures had random shapes, while the final shape became quite spherical.
      XRD analysis showed ZnO in a hexagonal structure, broadening in the diffracted
      peaks and going from larger to smaller particles along with a relaxation in the
      lattice constant c. The value of c was found to increase from 5.204 to 5.217 A
      with a decrease in particle size (600 to ~30 nm). PL result showed a new band at
      around 365 nm, whose intensity is found to increase as the particles size
      decreases. These remarkable structural and optical modifications induced in ZnO
      nanoparticles might prove useful for various applications. The increase in c
      value is an important factor for increasing the antibacterial effects of ZnO,
      suggesting that the HEBM technique is quite suitable for producing these
      nanoparticles for this purpose.

PMID- 21720500
TI  - A study on the preparation and characterization of plasmid DNA and drug
      containing magnetic nanoliposomes for the treatment of tumors.
AB  - PURPOSE: To explore the preparation and characterization of a novel nanosized
      magnetic liposome containing the PEI-As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) complex.
      METHODS: Mn(0.5)Zn(0.5)Fe(2)O(4) and As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4)
      nanoparticles were prepared by chemical coprecipitation and loaded with PEI. The
      PEI- As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) complex was characterized using
      transmission electron and scanning electron microscopy, X-ray diffraction, energy
      dispersive spectrometry, and Fourier transform infrared spectroscopy. Cell
      transfection experiments were performed to evaluate the transfect efficiency.
      Magnetic nanoliposomes were prepared by rotatory evaporation and their shape,
      diameter, and thermodynamic characteristics were observed. RESULTS:
      Mn(0.5)Zn(0.5)Fe(2)O(4) and PEI-As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles
      were spherical, with an average diameter of 20-40 nm. PEI
      As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) was an appropriate carrier for the delivery of
      a foreign gene to HepG2 cells. Energy dispersive spectrometry results confirmed
      the presence of the elements nitrogen and arsenic. Nanoliposomes of approximately
      100 nm were observed under a transmission electron microscope. Upon exposure to
      an alternating magnetic field, they also had good magnetic responsiveness, even
      though Mn(0.5)Zn(0.5)Fe(2)O(4)was modified by PEI and encased in liposomes.
      Temperatures increased to 37 degrees C-54 degrees C depending on different
      concentrations of PEI-As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4)and remained stable
      thereafter. CONCLUSION: Our results suggest that PEI
      As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) magnetic nanoliposomes are an excellent
      biomaterial, which has multiple benefits in tumor thermotherapy, gene therapy,
      and chemotherapy.

PMID- 21720501
TI  - Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer
      agents.
AB  - The effectiveness of anticancer agents may be hindered by low solubility in
      water, poor permeability, and high efflux from cells. Nanomaterials have been
      used to enable drug delivery with lower toxicity to healthy cells and enhanced
      drug delivery to tumor cells. Different nanoparticles have been developed using
      different polymers with or without surface modification to target tumor cells
      both passively and/or actively. Polylactide-co-glycolide (PLGA), a biodegradable
      polyester approved for human use, has been used extensively. Here we report on
      recent developments concerning PLGA nanoparticles prepared for cancer treatment.
      We review the methods used for the preparation and characterization of PLGA
      nanoparticles and their applications in the delivery of a number of active
      agents. Increasing experience in the field of preparation, characterization, and
      in vivo application of PLGA nanoparticles has provided the necessary momentum for
      promising future use of these agents in cancer treatment, with higher efficacy
      and fewer side effects.

PMID- 21720502
TI  - A novel spray-dried nanoparticles-in-microparticles system for formulating
      scopolamine hydrobromide into orally disintegrating tablets.
AB  - Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a
      colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a
      spray-drying method. The spray-dried microparticles were then formulated into
      orally disintegrating tablets (ODTs) using a wet granulation tablet formation
      process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of
      20% (w/w) were achieved for the microparticles, which ranged from 2 MUm to 8 MUm
      in diameter. Results of disintegration tests showed that the formulated ODTs
      could be completely dissolved within 45 seconds. Drug dissolution profiles
      suggested that SH is released more slowly from tablets made using the
      microencapsulation process compared with tablets containing SH that is free or in
      the form of nanoparticles. The time it took for 90% of the drug to be released
      increased significantly from 3 minutes for conventional ODTs to 90 minutes for
      ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked
      microparticles, it was thus possible to achieve an even lower drug release rate
      using tablets with appropriate chitosan crosslinking. Results obtained indicate
      that the development of new ODTs designed with crosslinked microparticles might
      be a rational way to overcome the unwanted taste of conventional ODTs and the
      side effects related to SH's intrinsic characteristics.

PMID- 21720503
TI  - Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles
      against cryptococcal meningitis in mice.
AB  - Amphotericin B deoxycholate (AmB), a classic antifungal drug, remains the initial
      treatment of choice for deep fungal infections, but it is not appropriate for
      treatment of cryptococcal meningitis due to its inability to pass through the
      blood-brain barrier (BBB). We examined the efficacy of amphotericin B
      polybutylcyanoacrylate nanoparticles (AmB-PBCA-NPs) modified with polysorbate 80
      that had a mean particle diameter less than 100 nanometers (69.0 +/- 28.6 nm).
      AmB-PBCA-NPs were detected in the brain 30 minutes after systemic administration
      into BALB/c mice and had a higher concentration than systemically administered
      AmB liposome (AmB-L, P < 0.05); AmB was not detected in the brain. Following
      infection for 24 hours and then 7 days of treatment, the survival rate of mice in
      the AmB-PBCA-NP group (80%) was significantly higher than that of the AmB (0%) or
      AmB-L (60%) treatment groups. Fungal load was also lower when assessed by colony
      forming unit counts obtained after plating infected brain tissue (P < 0.05). Our
      study indicates that AmB-PBCA-NPs with polysorbate 80 coating have the capacity
      to transport AmB across the BBB and is an efficient treatment against
      cryptococcal meningitis in a mouse model.

PMID- 21720504
TI  - Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin
      functionalized multiwalled carbon nanotubes.
AB  - The process of laser-mediated ablation of cancer cells marked with
      biofunctionalized carbon nanotubes is frequently called "nanophotothermolysis".
      We herein present a method of selective nanophotothermolisys of pancreatic cancer
      (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum
      albumin (HSA). With the purpose of testing the therapeutic value of these
      nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically
      resected specimens from patients with PC were preserved in a cold medium and kept
      alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra
      arterially administered in the greater pancreatic artery under ultrasound
      guidance. Confocal and transmission electron microscopy combined with
      immunohistochemical staining have confirmed the selective accumulation of HSA
      MWCNTs inside the human PC tissue. The external laser irradiation of the specimen
      has significantly produced extensive necrosis of the malign tissue after the
      intra-arterial administration of HSA-MWCNTs, without any harmful effects on the
      surrounding healthy parenchyma. We have obtained a selective photothermal
      ablation of the malign tissue based on the selective internalization of MWCNTs
      with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra
      arterial perfusion.

PMID- 21720505
TI  - Controlled release of chitosan/heparin nanoparticle-delivered VEGF enhances
      regeneration of decellularized tissue-engineered scaffolds.
AB  - Regeneration deficiency is one of the main obstacles limiting the effectiveness
      of tissue-engineered scaffolds. To develop scaffolds that are capable of
      accelerating regeneration, we created a heparin/chitosan nanoparticle-immobilized
      decellularized bovine jugular vein scaffold to increase the loading capacity and
      allow for controlled release of vascular endothelial growth factor (VEGF). The
      vascularization of the scaffold was evaluated in vitro and in vivo. The
      functional nanoparticles were prepared by physical self-assembly with a diameter
      of 67-132 nm, positive charge, and a zeta potential of ~30 mV and then the
      nanoparticles were successfully immobilized to the nanofibers of scaffolds by
      ethylcarbodiimide hydrochloride/hydroxysulfosuccinimide modification. The
      scaffolds immobilized with heparin/chitosan nanoparticles exhibited highly
      effective localization and sustained release of VEGF for several weeks in vitro.
      This modified scaffold significantly stimulated endothelial cells' proliferation
      in vitro. Importantly, utilization of heparin/chitosan nanoparticles to localize
      VEGF significantly increased fibroblast infiltration, extracellular matrix
      production, and accelerated vascularization in mouse subcutaneous implantation
      model in vivo. This study provided a novel and promising system for accelerated
      regeneration of tissue-engineering scaffolds.

PMID- 21720506
TI  - 3D culture of adult mouse neural stem cells within functionalized self-assembling
      peptide scaffolds.
AB  - Three-dimensional (3D) in vitro models of cell culture aim to fill the gap
      between the standard two-dimensional cell studies and the in vivo environment.
      Especially for neural tissue regeneration approaches where there is little
      regenerative capacity, these models are important for mimicking the extracellular
      matrix in providing support, allowing the natural flow of oxygen, nutrients, and
      growth factors, and possibly favoring neural cell regrowth. We have previously
      demonstrated that a new self-assembling nanostructured biomaterial, based on
      matrigel, was able to support adult neural stem cell (NSC) culture. In this
      study, we developed a new 3D cell culture system that takes advantage of the nano
      and microfiber assembling process, under physiologic conditions, of these
      biomaterials. The assembled scaffold forms an intricate and biologically active
      matrix that displays specifically designed functional motifs: RGD (Arg-Gly-Asp),
      BMHP1 (bone marrow homing peptide 1), and BMHP2, for the culture of adult NSCs.
      These scaffolds were prepared at different concentrations, and microscopic
      examination of the cell-embedded scaffolds showed that NSCs are viable and they
      proliferate and differentiate within the nanostructured environment of the
      scaffold. Such a model has the potential to be tailored to develop ad hoc
      designed peptides for specific cell lines.

PMID- 21720507
TI  - Blood cleaner on-chip design for artificial human kidney manipulation.
AB  - A novel design of a blood cleaner on-chip using an optical waveguide known as a
      PANDA ring resonator is proposed. By controlling some suitable parameters, the
      optical vortices (gradient optical fields/wells) can be generated and used to
      form the trapping tools in the same way as optical tweezers. In operation, the
      trapping force is formed by the combination between the gradient field and
      scattering photons by using the intense optical vortices generated within the
      PANDA ring resonator. This can be used for blood waste trapping and moves
      dynamically within the blood cleaner on-chip system (artificial kidney), and is
      performed within the wavelength routers. Finally, the blood quality test is
      exploited by the external probe before sending to the destination. The advantage
      of the proposed kidney on-chip system is that the unwanted substances can be
      trapped and filtered from the artificial kidney, which can be available for blood
      cleaning applications.

PMID- 21720508
TI  - Enhanced oral bioavailability of cyclosporine A by liposomes containing a bile
      salt.
AB  - The main purpose of this study was to evaluate liposomes containing a bile salt,
      sodium deoxycholate (SDC), as oral drug delivery systems to enhance the oral
      bioavailability of the poorly water-soluble and poorly permeable drug,
      cyclosporine A (CyA). Liposomes composed of soybean phosphatidylcholine (SPC) and
      SDC were prepared by a thin-film dispersion method followed by homogenization.
      Several properties of the liposomes including particle size, polydispersity
      index, and entrapment efficiency were characterized. The in vitro release of CyA
      from these liposomes was less than 5% at 12 hours as measured by a dynamic
      dialysis method. The pharmacokinetic results in rats showed improved absorption
      of CyA in SPC/SDC liposomes, compared with CyA-loaded conventional
      SPC/cholesterol (Chol) liposomes and microemulsion-based Sandimmune Neoral((r)).
      The relative oral bioavailability of CyA-loaded SPC/SDC and SPC/Chol liposomes
      was 120.3% and 98.6%, respectively, with Sandimmun Neoral as the reference. The
      enhanced bioavailability of CyA was probably due to facilitated absorption by the
      liposomes containing SDC rather than improved release rate.

PMID- 21720509
TI  - Type and composition of surfactants mediating gene transfection of
      polyethylenimine-coated liposomes.
AB  - BACKGROUND: The objective of this study was to compare the transfection
      efficiency of anionic liposomes coated with polyethylenimine (PEI) with that of
      PEI and Lipofectamine 2000(TM) using the plasmid DNA encoding green fluorescent
      protein in a human hepatoma (Huh7) cell line. METHODS: Factors affecting
      transfection efficiency, including type of surfactant, ratio of
      phosphatidylcholine (PC)/surfactant, carrier/DNA weight ratio, and the presence
      of serum have been investigated. Anionic liposomes, composed of PC and anionic
      surfactants, ie, sodium oleate (NaO), sodium taurocholate (NaT), or zwitterionic
      surfactant (3-[{3-cholamidopropyl}-dimethylammonio]-1-propanesulfonate, CHAPS) at
      molar ratios of 10:1, 10:1.5, and 10:2 were prepared by the sonication method.
      Subsequently, they were coated with PEI to produce polycationic liposomes (PCL).
      RESULTS: PCL was able to condense with pDNA depending on the PCL/DNA weight
      ratio. PCL composed of PC:NaO (10:2) showed higher transfection efficiency than
      NaT and CHAPS at all weight ratios tested. Higher transfection efficiency and
      gene expression were observed when the carrier/DNA weight ratio increased. The
      highest transfection efficiency was found at a weight ratio of 0.5. CONCLUSION:
      This PCL showed remarkably high transfection efficiency with low cytotoxicity to
      Huh7 cells in vitro, in comparison with PEI and Lipofectamine 2000.

PMID- 21720510
TI  - Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery
      system of hydroxysafflor yellow A.
AB  - BACKGROUND: A microemulsion is an effective formulation for improving the oral
      bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o)
      microemulsion was investigated as a system for enhancing the oral bioavailability
      of Biopharmaceutic Classification System (BCS) III drugs. METHODS: The
      microemulsion formulation was optimized using a pseudoternary phase diagram,
      comprising propylene glycol dicaprylocaprate (PG), Cremophor((r)) RH40, and water
      (30/46/24 w/w). RESULTS: The microemulsion increased the oral bioavailability of
      hydroxysafflor yellow A which was highly water-soluble but very poorly permeable.
      The relative bioavailability of hydroxysafflor yellow A microemulsion was about
      1937% compared with a control solution in bile duct-nonligated rats. However, the
      microemulsion showed lower enhanced absorption ability in bile duct-ligated rats,
      and the relative bioavailability was only 181%. In vitro experiments were further
      employed to study the mechanism of the enhanced effect of the microemulsion. In
      vitro lipolysis showed that the microemulsion was digested very quickly by
      pancreatic lipase. About 60% of the microemulsion was digested within 1 hour.
      Furthermore, the particle size of the microemulsion after digestion was very
      small (53.3 nm) and the digested microemulsion had high physical stability. An
      everted gut sac model demonstrated that cumulative transport of the digested
      microemulsion was significantly higher than that of the diluted microemulsion.
      CONCLUSION: These results suggested that digestion of the microemulsion by
      pancreatic lipase plays an important role in enhancing oral bioavailability of
      water-soluble drugs.

PMID- 21720511
TI  - Composite poly(vinyl alcohol)/poly(vinyl acetate) electrospun nanofibrous mats as
      a novel wound dressing matrix for controlled release of drugs.
AB  - The aim of this study was to develop novel biomedicated nanofiber electrospun
      mats for controlled drug release, especially drug release directly to an injury
      site to accelerate wound healing. Nanofibers of poly(vinyl alcohol) (PVA),
      poly(vinyl acetate) (PVAc), and a 50:50 composite blend, loaded with
      ciprofloxacin HCl (CipHCl), were successfully prepared by an electrospinning
      technique for the first time. The morphology and average diameter of the
      electrospun nanofibers were investigated by scanning electron microscopy. X-ray
      diffraction studies indicated an amorphous distribution of the drug inside the
      nanofiber blend. Introducing the drug into polymeric solutions significantly
      decreased solution viscosities as well as nanofiber diameter. In vitro drug
      release evaluations showed that both the kind of polymer and the amount of drug
      loaded greatly affected the degree of swelling, weight loss, and initial burst
      and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient
      method for electrospinning in order to control the rate and period of drug
      release in wound healing applications. Also, the thickness of the blend nanofiber
      mats strongly influenced the initial release and rate of drug release.

PMID- 21720512
TI  - New formulation of an old drug in hypertension treatment: the sustained release
      of captopril from cyclodextrin nanoparticles.
AB  - Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to
      be developed and is widely used in hypertension treatment. On the other hand,
      cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows
      formation of noncovalent inclusion complexes with appropriately sized guest
      molecules, thus modifying guest physical, chemical, and biological properties.
      Herein, the physicochemical characterization and in vivo ACE inhibition
      evaluation of seven CAP/CD complexes are reported. The inclusion complexes were
      prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and
      characterized by nuclear magnetic resonance, Fourier-transformed infrared
      spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning
      electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex
      administration (0.5 mg kg(-1) or 0.09 mg kg(-1), n = 4-7) to evaluate the ACE
      inhibition by continuous infusion of angiotensin I (30 ng 50 MUL(-1) min(-1)) in
      conscious Wistar rats. The physicochemical analysis demonstrated complete
      amorphization and complexation between CAP and CDs, indicating the substitution
      of water molecules inside the CD cavity with CAP. During the infusion of
      angiotensin I, the administration of all CAP/CD complexes induced a reduction in
      mean arterial pressure similar to that observed upon CAP administration. The
      nanoparticles obtained by the kneading method (CAP/alpha-CD:KM) showed a potent
      and long-lasting inhibitory activity (~22 hours) on the angiotensin I pressor
      effect. The results suggest that the inclusion complex of CAP and alpha-CD can
      function as a novel antihypertensive formulation that may improve therapeutic use
      of CAP by reducing its oral dose administration to once per day, thus providing
      better quality of life for almost 25% of the world's population who suffer from
      hypertension.

PMID- 21720513
TI  - Research progress on siRNA delivery with nonviral carriers.
AB  - RNA interference is a powerful method for the knockdown of pathologically
      relevant genes. Small interfering RNAs (siRNAs) have been widely demonstrated as
      effective biomedical genetic-therapy applications for many diseases.
      Unfortunately, siRNA duplexes are not ideal drug-like molecules. Problems
      hindering their effective application fundamentally lie in their delivery,
      stability, and off-target effects. Delivery systems provide solutions to many of
      the challenges facing siRNA therapeutics. Due to some fatal disadvantages of
      viral vectors, nonviral carriers have been studied extensively. Aside from
      liposomes, nanoparticles and cationic polymer carriers have exhibited improved in
      vivo stability, better biocompatibility, and efficiency for gene silencing with
      less cellular toxicity. They may represent a promising strategy for siRNA-based
      therapies, especially as nanomaterials. The present review also summarizes other
      methods of siRNA delivery and the side effects of the nanoparticles.

PMID- 21720514
TI  - Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron
      oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin.
AB  - The purpose of this study was to assess the induced apoptosis of self-assembled
      iron oxide magnetic nanoparticles (MNPs) co-loaded with daunorubicin (DNR) and 5
      bromotetrandrin (Br Tet) (DNR/Br Tet-MNPs), acting as a drug depot system for the
      sustained release of the loaded DNR and BrTet, in the drug resistant human
      leukemia K562/A02 cells and further to explore potential mechanisms. After being
      incubated for 48 hours, K562/A02 cells were treated with DNR/Br Tet-MNPs or DNR
      and Br Tet in solution (DNR/Br Tet-Sol). Morphologic characteristics of K562/A02
      cells were observed under a fluorescence microscope; cell apoptosis and
      intracellular accumulation of DNR were analyzed by FACS Calibur flow cytometry.
      Furthermore, reverse transcriptase polymerase chain reaction (RT-PCR) and Western
      blotting analyses were performed to study the apoptosis associated gene
      transcription and protein expression, respectively. Typical apoptotic
      characteristics, including chromatin condensation and fragmentation of nuclei,
      were observed and a high rate of apoptosis was detected in K562/A02 cells treated
      with DNR/Br Tet-MNPs and DNR/Br Tet-Sol. Detection of relative fluorescence
      intensity of intracellular DNR demonstrated that intracellular DNR was higher in
      K562/A02 cells treated with DNR/Br Tet-MNPs than that of DNR/Br Tet-Sol. Further
      study demonstrated that both DNR/Br Tet-MNPs and DNR/Br Tet-Sol reduced the gene
      transcriptions and protein expressions of bcl-2 and survivin and enhanced that of
      bax and caspase 3. It is concluded that self-assembled DNR/Br Tet-MNPs, as one of
      the potential antitumor agents for hematologic malignancies, may effectively
      induce apoptosis of K562/A02 cells through elevating the ratio of bax/bcl-2,
      activating caspase 3, and inactivating survivin.

PMID- 21720515
TI  - Self-assembled rosette nanotubes encapsulate and slowly release dexamethasone.
AB  - Rosette nanotubes (RNTs) are novel, self-assembled, biomimetic, synthetic drug
      delivery materials suitable for numerous medical applications. Because of their
      amphiphilic character and hollow architecture, RNTs can be used to encapsulate
      and deliver hydrophobic drugs otherwise difficult to deliver in biological
      systems. Another advantage of using RNTs for drug delivery is their
      biocompatibility, low cytotoxicity, and their ability to engender a favorable,
      biologically-inspired environment for cell adhesion and growth. In this study, a
      method to incorporate dexamethasone (DEX, an inflammatory and a bone growth
      promoting steroid) into RNTs was developed. The drug-loaded RNTs were
      characterized using diffusion ordered nuclear magnetic resonance spectroscopy
      (DOSY NMR) and UV-Vis spectroscopy. Results showed for the first time that DEX
      can be easily and quickly encapsulated into RNTs and released to promote
      osteoblast (bone-forming cell) functions over long periods of time. As a result,
      RNTs are presented as a novel material for the targeted delivery of hydrophobic
      drugs otherwise difficult to deliver.

PMID- 21720516
TI  - Ethylenediamine functionalized-single-walled nanotube (f-SWNT)-assisted in vitro
      delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells.
AB  - A gene delivery concept based on ethylenediamine-functionalized single-walled
      carbon nanotubes (f-SWCNTs) using the oncogene suppressor p53 gene as a model
      gene was successfully tested in vitro in MCF-7 breast cancer cells. The f-SWCNTs
      p53 complexes were introduced into the cell medium at a concentration of 20 MUg
      mL(-1) and cells were exposed for 24, 48, and 72 hours. Standard ethidium bromide
      and acridine orange assays were used to detect apoptotic cells and indicated that
      a significantly larger percentage of the cells (approx 40%) were dead after 72
      hours of exposure to f-SWCNTs-p53 as compared to the control cells, which were
      exposed to only p53 or f-SWCNTs, respectively. To further support the uptake and
      expression of the genes within the cells, green fluorescent protein-tagged p53,
      attached to the f-SWCNTs was added to the medium and the complex was observed to
      be strongly expressed in the cells. Moreover, caspase 3 activity was found to be
      highly enhanced in cells incubated with the f-SWCNTs-p53 complex, indicating
      strongly induced apoptosis. This system could be the foundation for novel gene
      delivery platforms based on the unique structural and morphological properties of
      multi-functional nanomaterials.

PMID- 21720517
TI  - The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib
      microspheres.
AB  - The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2
      enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific
      drug delivery to colorectal tumors. Film coating was done with the pH-sensitive
      polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the
      core. The microspheres were characterized by X-ray diffraction, differential
      scanning calorimetry, and Fourier transform infrared spectroscopy and were
      evaluated for particle size, drug load, in vitro drug release, release kinetics,
      accelerated stability, and extent of mucoadhesion. The coated microspheres
      released the drug at pH 7.4, the putative parameter for colonic delivery. When
      applied to the mucosal surface of freshly excised goat colon, microspheres
      pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To
      ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5
      dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using
      both valdecoxib and coated microspheres. In both cases, the percentage of
      dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the
      tested concentration range. Drug transport studies of the drug as well as the
      coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were
      conducted. The microspheres were found to exhibit slower and delayed drug release
      and lower intracellular concentration of valdecoxib.

PMID- 21720518
TI  - UNMIX modeling of ambient PM(2.5) near an interstate highway in Cincinnati, OH,
      USA.
AB  - The "Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS)" is underway
      to determine if infants who are exposed to diesel engine exhaust particles are at
      an increased risk for atopy and atopic respiratory disorders, and to determine if
      this effect is magnified in a genetically at risk population. In support of this
      study, a methodology has been developed to allocate local traffic source
      contributions to ambient PM(2.5) in the Cincinnati airshed. As a first step
      towards this allocation, UNMIX was used to generate factors for ambient PM(2.5)
      at two sites near at interstate highway. Procedures adopted to collect, analyze
      and prepare the data sets to run UNMIX are described. The factors attributed to
      traffic sources were similar for the two sites. These factors were also similar
      to locally measured truck engine-exhaust enriched ambient profiles. The temporal
      variation of the factors was analyzed with clear differences observed between
      factors attributed to traffic sources and combustion-related regional secondary
      sources.

PMID- 21720519
TI  - Motor Planning under Unpredictable Reward: Modulations of Movement Vigor and
      Primate Striatum Activity.
AB  - Although reward probability is an important factor that shapes animal's behavior,
      it is not well understood how the brain translates reward expectation into the
      vigor of movement [reaction time (RT) and speed]. To address this question, we
      trained two monkeys in a RT task that required wrist movements in response to
      vibrotactile and visual stimuli, with a variable reward schedule. Correct
      performance was rewarded in 75% of the trials. Monkeys were certain that they
      would be rewarded only in the trials immediately following withheld rewards. In
      these trials, the animals responded sooner and moved faster. Single-unit
      recordings from the dorsal striatum revealed modulations in neural firing that
      reflected changes in movement vigor. First, in the trials with certain rewards,
      striatal neurons modulated their firing rates earlier. Second, magnitudes of
      changes in neuronal firing rates depended on whether or not monkeys were certain
      about the reward. Third, these modulations depended on the sensory modality of
      the cue (visual vs. vibratory) and/or movement direction (flexions vs.
      extensions). We conclude that dorsal striatum may be a part of the mechanism
      responsible for the modulation of movement vigor in response to changes of reward
      predictability.

PMID- 21720520
TI  - Decoding continuous variables from neuroimaging data: basic and clinical
      applications.
AB  - The application of statistical machine learning techniques to neuroimaging data
      has allowed researchers to decode the cognitive and disease states of
      participants. The majority of studies using these techniques have focused on
      pattern classification to decode the type of object a participant is viewing, the
      type of cognitive task a participant is completing, or the disease state of a
      participant's brain. However, an emerging body of literature is extending these
      classification studies to the decoding of values of continuous variables (such as
      age, cognitive characteristics, or neuropsychological state) using high
      dimensional regression methods. This review details the methods used in such
      analyses and describes recent results. We provide specific examples of studies
      which have used this approach to answer novel questions about age and cognitive
      and disease states. We conclude that while there is still much to learn about
      these methods, they provide useful information about the relationship between
      neural activity and age, cognitive state, and disease state, which could not have
      been obtained using traditional univariate analytical methods.

PMID- 21720521
TI  - Phosphorylation via PKC Regulates the Function of the Drosophila Odorant Co
      Receptor.
AB  - Insect odorant receptors (ORs) have a unique design of heterodimers formed by an
      olfactory receptor protein and the ion channel Orco. Heterologously expressed
      insect ORs are activated via an ionotropic and a metabotropic pathway that leads
      to cAMP production and activates the Orco channel. The contribution of
      metabotropic signaling to the insect odor response remains to be elucidated.
      Disruption of the G(q) protein signaling cascade reduces the odor response (Kain
      et al., 2008). We investigated this phenomenon in HEK293 cells expressing
      Drosophila Orco and found that phospholipase C (PLC) inhibition reduced the
      sensitivity of Orco to cAMP. A similar effect was seen upon inhibition of protein
      kinase C (PKC), whereas PKC stimulation activated Orco even in the absence of
      cAMP. Mutation of the five PKC phosphorylation sites in Orco almost completely
      eliminated sensitivity to cAMP. To test the impact of PKC activity in vivo we
      combined single sensillum electrophysiological recordings with microinjection of
      agents affecting PLC and PKC function and observed an altered response of
      olfactory sensory neurons (OSNs) to odorant stimulation. Injection of the PLC
      inhibitor U73122 or the PKC inhibitor Go6976 into sensilla reduced the OSN
      response to odor pulses. Conversely, injection of the PKC activators OAG, a
      diacylglycerol analog, or phorbol myristate acetate (PMA) enhanced the odor
      response. We conclude that metabotropic pathways affecting the phosphorylation
      state of Orco regulate OR function and thereby shape the OSN odor response.

PMID- 21720522
TI  - Experience-induced interocular plasticity of vision in infancy.
AB  - Animal model studies of amblyopia have generally concluded that enduring effects
      of monocular deprivation (MD) on visual behavior (i.e., loss of visual acuity)
      are limited to the deprived eye, and are restricted to juvenile life. We have
      previously reported, however, that lasting effects of MD on visual function can
      be elicited in adulthood by stimulating visuomotor experience through the non
      deprived eye. To test whether stimulating experience would also induce
      interocular plasticity of vision in infancy, we assessed in rats from eye-opening
      on postnatal day (P) 15, the effect of pairing MD with the daily experience of
      measuring thresholds for optokinetic tracking (OKT). MD with visuomotor
      experience from P15 to P25 led to a ~60% enhancement of the spatial frequency
      threshold for OKT through the non-deprived eye during the deprivation, which was
      followed by loss-of-function (~60% below normal) through both eyes when the
      deprived eye was opened. Reduced thresholds were maintained into adulthood with
      binocular OKT experience from P25 to P30. The ability to generate the plasticity
      and maintain lost function was dependent on visual cortex. Strictly limiting the
      period of deprivation to infancy by opening the deprived eye at P19 resulted in a
      comparable loss-of-function. Animals with reduced OKT responses also had
      significantly reduced visual acuity, measured independently in a discrimination
      task. Thus, experience-dependent cortical plasticity that can lead to amblyopia
      is present earlier in life than previously recognized.

PMID- 21720523
TI  - Altered Balance of Activity in the Striatal Direct and Indirect Pathways in Mouse
      Models of Huntington's Disease.
AB  - Imbalance in the activity of striatal direct and indirect pathway neurons
      contributes to motor disturbances in several neurodegenerative diseases. In
      Huntington's disease (HD), indirect pathway [dopamine (DA) D2 receptor
      expressing] medium-sized spiny neurons (MSNs) are believed to show earlier
      vulnerability than direct pathway MSNs. We examined synaptic activity and DA
      modulation in MSNs forming the direct and indirect pathways in YAC128 and BACHD
      mouse models of HD. To visualize the two types of MSNs, we used mice expressing
      enhanced green fluorescent protein under the control of the promoter for the DA
      D1 or D2 receptor. Experiments were performed in early symptomatic (1.5 months)
      and symptomatic (12 months) mice. Behaviorally, early symptomatic mice showed
      increased stereotypies while symptomatic mice showed decreased motor activity.
      Electrophysiologically, at the early stage, excitatory and inhibitory
      transmission onto D1-YAC128 and D1-BACHD MSNs were increased, while there was no
      change in D2 MSNs. DA modulation of spontaneous excitatory postsynaptic currents
      (sEPSCs) in slices was absent in YAC128 cells at the early stage, but was
      restored by treating the slices with the DA depleter tetrabenazine (TBZ). In
      BACHD mice TBZ restored paired-pulse ratios and a D1 receptor antagonist induced
      a larger decrease of sEPSCs than in D1-WT cells, suggesting increased DA tone.
      Finally, TBZ decreased stereotypies in BACHD mice. These results indicate that by
      reducing DA or antagonizing D1 receptors, increases in inhibitory and excitatory
      transmission in early phenotypic direct pathway neurons can be normalized. In
      symptomatic YAC128 mice, excitatory synaptic transmission onto D1 MSNs was
      decreased, while inhibitory transmission was increased in D2 MSNs. These studies
      provide evidence for differential and complex imbalances in glutamate and GABA
      transmission, as well as in DA modulation, in direct and indirect pathway MSNs
      during HD progression.

PMID- 21720524
TI  - Functional Changes in Neocortical Activity in Huntington's Disease Model Mice: An
      in vivo Intracellular Study.
AB  - Studies of animal models of Huntington's disease (HD) have revealed that
      neocortical and neostriatal neurons of these animals in vitro exhibit a number of
      morphological and physiological changes, including increased input resistance and
      changes in neocortical synaptic inputs. We measured the functional effects of
      polyglutamate accumulation in neocortical neurons in R6/2 mice (8-14 weeks of
      age) and their age-matched non-transgenic littermates using in vivo intracellular
      recordings. All neurons showed spontaneous membrane potential fluctuations. The
      current/voltage and the firing properties of the HD neocortical neurons were
      significantly altered, especially in the physiologically relevant current range
      around and below threshold. As a result, membrane potential transitions from the
      Down state to Up state were evoked with smaller currents in HD neocortical
      neurons than in controls. The excitation-to-frequency curves of the HD mice were
      significantly steeper than those of controls, indicating a smaller input-output
      dynamic range for these neurons. Increased likelihood of Down to Up state
      transitions could cause pathological recruitment of corticostriatal assemblies by
      increasing correlated neuronal activity. We measured coherence of the in vivo
      intracellular recordings with simultaneously recorded electrocorticograms. We
      found that the peak of the coherence at <5 Hz was significantly smaller in the HD
      animals, indicating that the amount of coherence in the state transitions of
      single neurons is less correlated with global activity than non-transgenic
      controls. We propose that decreased correlation of neocortical inputs may be a
      major physiological cause underlying the errors in sensorimotor pattern
      generation in HD.

PMID- 21720525
TI  - The Vertebrate Brain, Evidence of Its Modular Organization and Operating System:
      Insights into the Brain's Basic Units of Structure, Function, and Operation and
      How They Influence Neuronal Signaling and Behavior.
AB  - The human brain is a complex organ made up of neurons and several other cell
      types, and whose role is processing information for use in eliciting behaviors.
      However, the composition of its repeating cellular units for both structure and
      function are unresolved. Based on recent descriptions of the brain's
      physiological "operating system", a function of the tri-cellular metabolism of N
      acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) for supply of energy,
      and on the nature of "neuronal words and languages" for intercellular
      communication, insights into the brain's modular structural and functional units
      have been gained. In this article, it is proposed that the basic structural unit
      in brain is defined by its physiological operating system, and that it consists
      of a single neuron, and one or more astrocytes, oligodendrocytes, and vascular
      system endothelial cells. It is also proposed that the basic functional unit in
      the brain is defined by how neurons communicate, and consists of two neurons and
      their interconnecting dendritic-synaptic-dendritic field. Since a functional unit
      is composed of two neurons, it requires two structural units to form a functional
      unit. Thus, the brain can be envisioned as being made up of the three-dimensional
      stacking and intertwining of myriad structural units which results not only in
      its gross structure, but also in producing a uniform distribution of binary
      functional units. Since the physiological NAA-NAAG operating system for supply of
      energy is repeated in every structural unit, it is positioned to control global
      brain function.

PMID- 21720526
TI  - Online adaptation and over-trial learning in macaque visuomotor control.
AB  - When faced with unpredictable environments, the human motor system has been shown
      to develop optimized adaptation strategies that allow for online adaptation
      during the control process. Such online adaptation is to be contrasted to slower
      over-trial learning that corresponds to a trial-by-trial update of the movement
      plan. Here we investigate the interplay of both processes, i.e., online
      adaptation and over-trial learning, in a visuomotor experiment performed by
      macaques. We show that simple non-adaptive control schemes fail to perform in
      this task, but that a previously suggested adaptive optimal feedback control
      model can explain the observed behavior. We also show that over-trial learning as
      seen in learning and aftereffect curves can be explained by learning in a radial
      basis function network. Our results suggest that both the process of over-trial
      learning and the process of online adaptation are crucial to understand
      visuomotor learning.

PMID- 21720527
TI  - Postsurgical paracicatricial cutaneous satellitosis of giant cell tumour of the
      tendon sheath, localized type.
AB  - Tenosynovial giant cell tumour (localized type) is a tumour of tendon sheaths and
      interphalangeal joints, affecting the digits and arising from the synovium. It is
      characterized by a proliferation of mononuclear cells and osteoclast-like
      polykaryocytes. Its propagation to the skin is an exceptional event, which can
      take place either in localized form in the fingertips (localized type) or in the
      rare diffuse form called giant cell tumour of the tendon sheath (diffuse type).
      We report here a case of giant cell tumour with cutaneous satellites, which
      appeared close to and around the surgical scar following the excision of the
      primary lesion, in a 9-year-old boy. In the cutaneous satellites, a few signs of
      transformation could be observed, consisting of the lack of stroma and pronounced
      cellularity characterized by sheets of rounded synovial-like cells admixed with
      multinucleated giant cells and xanthoma cells. No relapse was observed 1 year
      after a plastic surgery procedure (complete replacement of the involved skin).
      Diffuse lesions usually represent a diagnostic problem in comparison with their
      localized counterparts. The malignant transformation of an originally typical
      tenosynovial giant cell tumour is a rare but well-documented event. Our case
      seems to represent a typical example because the pronounced cellularity might
      wrongly lead to a diagnosis of malignancy.

PMID- 21720528
TI  - A patient with fragile x-associated tremor/ataxia syndrome presenting with
      executive cognitive deficits and cerebral white matter lesions.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset
      neurodegenerative disorder that primarily affects males who are carriers of a
      premutation of a CGG expansion in the FMR1 gene. In Asian populations, FXTAS has
      rarely been reported. Here, we report the case of a Japanese FXTAS patient who
      showed predominant executive cognitive deficits as the main feature of his
      disease. In contrast, the patient exhibited only very mild symptoms of intention
      tremor and ataxia, which did not interfere with daily activities. A gene analysis
      revealed that the patient carried a premutation of a CGG expansion (111 CGG
      repeats) in the FMR1 gene. The mRNA expression level of FMR1 in the patient was
      1.5-fold higher than in controls. On brain MRI scans, fluid-attenuated inversion
      recovery images showed high-intensity lesions in the middle cerebellar peduncles
      and the cerebral white matter, with a frontal predominance. The present case
      extends previous notions regarding the cognitive impairment in FXTAS patients.
      Recognizing FXTAS patients with predominant cognitive impairment from various
      ethnic backgrounds would contribute to our understanding of the phenotypic
      variation of this disease.

PMID- 21720529
TI  - Recurrent subarachnoid bleeding and superficial siderosis in a patient with
      histopathologically proven cerebral amyloid angiopathy.
AB  - A 68-year-old man with a history of hypertension presented with recurrent
      subarachnoid bleeding. Brain MRI showed superficial siderosis, and diagnostic
      cerebral angiograms did not show any intracranial vascular malformation or
      arterial aneurism. Post mortem neuropathological examination of the brain was
      consistent with a diagnosis of cerebral amyloid angiopathy. Clinicians should be
      aware that cerebral amyloid angiopathy should be considered in patients with
      unexplained recurrent subarachnoid bleeding, even in cases without familial
      clustering or transthyretin variant.

PMID- 21720530
TI  - Cerebral localized marginal zone lymphoma presenting as hypothalamic-pituitary
      region disorder.
AB  - INTRODUCTION: Marginal zone B-cell lymphoma is a rare disease which can be
      considerably difficult to recognize and diagnose when signs of systemic
      involvement are absent. CASE PRESENTATION: We report the case of a 57-year-old
      woman with initial olfactory disturbance, followed by psychosis, diabetes
      insipidus and hypothalamic eating disorder as an uncommon clinical presentation
      of marginal zone B-cell lymphoma. CONCLUSION: Marginal zone B-cell lymphoma
      should be considered as a potential differential diagnosis in patients with
      hypothalamic disturbances.

PMID- 21720531
TI  - Can we measure memes?
AB  - Memes are the fundamental unit of cultural evolution and have been left upon the
      periphery of cognitive neuroscience due to their inexact definition and the
      consequent presumption that they are impossible to measure. Here it is argued
      that although a precise definition of memes is rather difficult it does not
      preclude highly controlled experiments studying the neural substrates of their
      initiation and replication. In this paper, memes are termed as either internally
      or externally represented (i-memes/e-memes) in relation to whether they are
      represented as a neural substrate within the central nervous system or in some
      other form within our environment. It is argued that neuroimaging technology is
      now sufficiently advanced to image the connectivity profiles of i-memes and
      critically, to measure changes to i-memes over time, i.e., as they evolve. It is
      argued that it is wrong to simply pass off memes as an alternative term for
      "stimulus" and "learnt associations" as it does not accurately account for the
      way in which natural stimuli may dynamically "evolve" as clearly observed in our
      cultural lives.

PMID- 21720532
TI  - Cataract Surgery in Behcet's Disease Patients One Week after Infliximab
      Administration.
AB  - PURPOSE: To describe two patients with Behcet's disease who underwent cataract
      surgery one week after infliximab administration. METHODS: Patients received
      preoperative antibiotic therapy with 0.5% levofloxacin eye drops and 500 mg
      levofloxacin oral tablets, followed by cataract surgery one week after infliximab
      administration. We observed ocular findings following cataract surgery,
      phacoemulsification-aspiration, and posterior chamber intraocular lens
      implantation. RESULTS: There were no intraoperative complications. Neither ocular
      inflammatory attacks nor infectious complications were found in the operated eyes
      of both patients during follow-up. CONCLUSION: Administration of infliximab one
      week before cataract surgery is safe and effective for patients with Behcet's
      disease.

PMID- 21720533
TI  - Fibrocellular contraction of a lamellar posterior corneal graft.
AB  - PURPOSE: To report a case of progressive fibrotic contraction of the posterior
      lamellar graft after initially successful Descemet's stripping automated
      endothelial keratoplasty (DSAEK). METHODS: Retrospective report of clinical data
      and histopathological analysis of excised corneal tissue. RESULTS: A 63-year-old
      woman underwent uncomplicated DSAEK in her left eye due to endothelial dystrophy.
      During the first months after surgery, her visual acuity was 0.3, and a semilunar
      contraction gradually appeared at the edge of the graft. Over the following
      months, the fibrotic changes progressed and visual acuity decreased, with no
      improvement after uncomplicated cataract surgery. A successful penetrating
      keratoplasty was performed, and the excised corneal button with an attached
      posterior lamellar graft was histologically examined. The affected part of the
      graft consisted of a thickened fibrocellular tissue positive for
      glycosaminoglycans and smooth muscle actin. CONCLUSIONS: The present case
      demonstrates asymmetric fibrotic contraction of a DSAEK graft.

PMID- 21720534
TI  - Flat choroidal nevus inaccessible to ultrasound sonography evaluated by enhanced
      depth imaging optical coherence tomography.
AB  - PURPOSE: To demonstrate the usefulness of enhanced depth imaging optical
      coherence tomography (EDI-OCT) in investigating choroidal lesions inaccessible to
      ultrasound sonography. METHODS: In a 60-year-old woman with an asymptomatic
      choroidal nevus, normal OCT was used to observe the macula and EDI-OCT to image
      the choroidal nevus that was inaccessible to ultrasound. The exact location of
      the lesion in the choroid and the dimensions of the nevus were measured. RESULTS:
      The lesion was located in the superior macula, and the nevus was homogeneous in
      its reflectivity. We observed a thickened choroid delineated by the shadow cone
      behind it, measuring 1,376 * 325 MUm in the larger vertical cut and 1,220 * 325
      MUm in the larger horizontal cut in an image with a 1:1 pixel mapping and
      automatic zoom. The macular profile and thickness were both normal. CONCLUSIONS:
      EDI-OCT appears to be an excellent technique for measuring choroidal nevi and all
      choroidal lesions accessible to OCT imaging by depicting their exact location in
      the choroid, their dimensions, and their demarcation from the surrounding healthy
      tissue, thus allowing for a more efficient and accurate follow-up.

PMID- 21720535
TI  - Clinical Course before and after Cataract and Glaucoma Surgery under Systemic
      Infliximab Therapy in Patients with Behcet's Disease.
AB  - PURPOSE: Patients with Behcet's disease often need intraocular surgeries for the
      treatment of secondary cataract or glaucoma. This study aims to report the
      clinical course before and after the intraocular surgeries of 5 patients who were
      systematically treated with infliximab. METHODS: Retrospective case series.
      RESULTS: Seven eyes of 5 male patients with Behcet's disease, who underwent
      intraocular surgery while under systemic infliximab therapy at Yokohama City
      University Hospital from 2007 to 2009, were included in the study. The mean age
      at surgery was 44.2 years. Phacoemulsification was performed on 4 eyes, and
      trabeculectomy was done on the remaining 3 eyes. The mean duration since the
      onset of the ocular symptoms was 107 months. Control of the ocular attacks with
      the use of other systemic medications was difficult for all patients; however,
      the use of infliximab enabled adequate control of the attacks. The visual acuity
      status during the preoperative stage did not worsen during the postoperative
      period. No infectious complication was observed in all cases. CONCLUSIONS: Our
      results suggest that infliximab treatment does not complicate any subsequent
      intraocular surgery. Patients with Behcet's disease in need of intraocular
      surgery can benefit from control of attacks with infliximab treatment.

PMID- 21720536
TI  - Toward a multi-scale computational model of arterial adaptation in hypertension:
      verification of a multi-cell agent based model.
AB  - Agent-based models (ABMs) represent a novel approach to study and simulate
      complex mechano chemo-biological responses at the cellular level. Such models
      have been used to simulate a variety of emergent responses in the vasculature,
      including angiogenesis and vasculogenesis. Although not used previously to study
      large vessel adaptations, we submit that ABMs will prove equally useful in such
      studies when combined with well-established continuum models to form multi-scale
      models of tissue-level phenomena. In order to couple agent-based and continuum
      models, however, there is a need to ensure that each model faithfully represents
      the best data available at the relevant scale and that there is consistency
      between models under baseline conditions. Toward this end, we describe the
      development and verification of an ABM of endothelial and smooth muscle cell
      responses to mechanical stimuli in a large artery. A refined rule-set is proposed
      based on a broad literature search, a new scoring system for assigning confidence
      in the rules, and a parameter sensitivity study. To illustrate the utility of
      these new methods for rule selection, as well as the consistency achieved with
      continuum-level models, we simulate the behavior of a mouse aorta during
      homeostasis and in response to both transient and sustained increases in
      pressure. The simulated responses depend on the altered cellular production of
      seven key mitogenic, synthetic, and proteolytic biomolecules, which in turn
      control the turnover of intramural cells and extracellular matrix. These events
      are responsible for gross changes in vessel wall morphology. This new ABM is
      shown to be appropriately stable under homeostatic conditions, insensitive to
      transient elevations in blood pressure, and responsive to increased intramural
      wall stress in hypertension.

PMID- 21720537
TI  - Maternal neural responses to infant cries and faces: relationships with substance
      use.
AB  - Substance abuse in pregnant and recently post-partum women is a major public
      health concern because of effects on the infant and on the ability of the adult
      to care for the infant. In addition to the negative health effects of teratogenic
      substances on fetal development, substance use can contribute to difficulties
      associated with the social and behavioral aspects of parenting. Neural circuits
      associated with parenting behavior overlap with circuits involved in addiction
      (e.g., frontal, striatal, and limbic systems) and thus may be co-opted for the
      craving/reward cycle associated with substance use and abuse and be less
      available for parenting. The current study investigates the degree to which
      neural circuits associated with parenting are disrupted in mothers who are
      substance-using. Specifically, we used functional magnetic resonance imaging to
      examine the neural response to emotional infant cues (faces and cries) in
      substance-using compared to non-using mothers. In response to both faces (of
      varying emotional valence) and cries (of varying distress levels), substance
      using mothers evidenced reduced neural activation in regions that have been
      previously implicated in reward and motivation as well as regions involved in
      cognitive control. Specifically, in response to faces, substance users showed
      reduced activation in prefrontal regions, including the dorsolateral and
      ventromedial prefrontal cortices, as well as visual processing (occipital lobes)
      and limbic regions (parahippocampus and amygdala). Similarly, in response to
      infant cries, substance-using mothers showed reduced activation relative to non
      using mothers in prefrontal regions, auditory sensory processing regions, insula
      and limbic regions (parahippocampus and amygdala). These findings suggest that
      infant stimuli may be less salient for substance-using mothers, and such reduced
      saliency may impair developing infant-caregiver attachment and the ability of
      mothers to respond appropriately to their infants.

PMID- 21720538
TI  - Assessing signal-driven mechanisms in neonates: brain responses to temporally and
      spectrally different sounds.
AB  - Past studies have found that, in adults, the acoustic properties of sound signals
      (such as fast versus slow temporal features) differentially activate the left and
      right hemispheres, and some have hypothesized that left-lateralization for speech
      processing may follow from left-lateralization to rapidly changing signals. Here,
      we tested whether newborns' brains show some evidence of signal-specific
      lateralization responses using near-infrared spectroscopy (NIRS) and auditory
      stimuli that elicits lateralized responses in adults, composed of segments that
      vary in duration and spectral diversity. We found significantly greater bilateral
      responses of oxygenated hemoglobin (oxy-Hb) in the temporal areas for stimuli
      with a minimum segment duration of 21 ms, than stimuli with a minimum segment
      duration of 667 ms. However, we found no evidence for hemispheric asymmetries
      dependent on the stimulus characteristics. We hypothesize that acoustic-based
      functional brain asymmetries may develop throughout early infancy, and discuss
      their possible relationship with brain asymmetries for language.

PMID- 21720539
TI  - Bioluminescent diagnostic imaging to characterize altered respiratory tract
      colonization by the burkholderia pseudomallei capsule mutant.
AB  - Pneumonia is a common manifestation of the potentially fatal disease melioidosis,
      caused by the select agent bacteria Burkholderia pseudomallei. In this study we
      describe a new model system to investigate pulmonary melioidosis in vivo using
      bioluminescent-engineered bacteria in a murine respiratory disease model. Studies
      were performed to validate that the stable, light producing B. pseudomallei
      strain JW280 constitutively produced light in biologically relevant host-pathogen
      interactions. Hairless outbred SKH1 mice were used to enhance the ability to
      monitor B. pseudomallei respiratory disease, and were found to be similarly
      susceptible to respiratory melioidosis as BALB/c mice. This represents the first
      demonstration of in vivo diagnostic imaging of pulmonary melioidosis permitting
      the detection of B. pseudomallei less than 24 h post-infection. Diagnostic
      imaging of pulmonary melioidosis revealed distinct temporal patterns of bacterial
      colonization unique to both BALB/c and SKH1 mice. Validation of these model
      systems included the use of the previously characterized capsule mutant, which
      was found to colonize the upper respiratory tract at significantly higher levels
      than the wild type strain. These model systems allow for high resolution
      detection of bacterial pulmonary disease which will facilitate studies of
      therapeutics and basic science evaluation of melioidosis.

PMID- 21720540
TI  - Treatment of depression as part of end-of-life care.
AB  - We present a case report of a severe treatment resistant major depressive episode
      in a patient with advanced cancer and limited life expectancy which resolved
      completely within 10 days of commencing combination therapy involving mirtazepine
      and paroxetine. Aggressive treatment of clinical depression even in the context
      of short life expectancy (that is, a short number of weeks) can dramatically
      reduce patient and family distress and improve quality of life.

PMID- 21720541
TI  - The C20orf133 gene is disrupted in a patient with Kabuki syndrome.
AB  - Kabuki syndrome (KS) is a rare, congenital mental retardation syndrome. The
      aetiology of KS remains unknown. Four carefully selected patients with KS were
      screened for chromosomal imbalances using array comparative genomic hybridisation
      at 1 Mb resolution. In one patient, a 250 kb de novo microdeletion at 20p12.1 was
      detected, deleting exon 5 of C20orf133. The function of this gene is unknown. In
      situ hybridisation with the mouse orthologue of C20orf133 showed expression
      mainly in brain. The de novo nature of the deletion, the expression data and the
      fact that C20orf133 carries a macro domain, suggesting a role for the gene in
      chromatin biology, make the gene a likely candidate to cause the phenotype in
      this patient with KS. Both the finding of different of chromosomal rearrangements
      in patients with KS features and the absence of C20orf133 mutations in 19
      additional patients with KS suggest that KS is genetically heterogeneous.

PMID- 21720542
TI  - Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal
      recessive cataract.
AB  - GJA8 encodes connexin-50, a gap junction protein in the eye lens. Mutations in
      GJA8 have been reported in families with autosomal dominant cataract. The
      objective of this report was to identify the disease gene in a family with
      congenital cataract of autosomal recessive inheritance. Eight candidate genes
      were screened for pathogenic alterations in affected and unaffected family
      members and in normal unrelated controls. A single base insertion leading to
      frameshift at codon 203 of connexin 50 was found to co-segregate with disease in
      the family. These results confirm involvement of GJA8 in autosomal recessive
      cataract.

PMID- 21720543
TI  - Manganese superoxide dismutase deficiency exacerbates ischemic brain damage under
      hyperglycemic conditions by altering autophagy.
AB  - Both preischemic hyperglycemia and suppression of SOD2 activity aggravate
      ischemic brain damage. This study was undertaken to assess the effect of SOD2
      mutation on ischemic brain damage and its relation to the factors involved in
      autophagy regulation in hyperglycemic wild-type (WT) and heterozygous SOD2
      knockout (SOD2(-/+)) mice subjected to 30-min transient focal ischemia. The brain
      samples were analyzed at 5 and 24 h after recirculation for ischemic lesion
      volume, superoxide production, and oxidative DNA damage and protein levels of
      Beclin 1, damage-regulated autophagy modulator (DRAM), and microtubule-associated
      protein 1 light chain 3 (LC3). The results revealed a significant increase in
      infarct volume in hyperglycemic SOD2(-/+) mice, and this was accompanied with an
      early (5 h) significant rise in superoxide production and reduced SOD2 activity
      in SOD2(-/+) mice as compared to WT mice. The superoxide production is associated
      with oxidative DNA damage as indicated by colocalization of the dihydroethidium
      (DHE) signal with 8-OHdG fluorescence in SOD2(-/+) mice. In addition, while
      ischemia in WT hyperglycemics increased the levels of autophagy markers Beclin 1,
      DRAM, and LC3, ischemia in hyperglycemic, SOD2-deficient mice suppressed the
      levels of autophagy stimulators. These results suggest that SOD2 knockdown
      exacerbates ischemic brain damage under hyperglycemic conditions via increased
      oxidative stress and DNA oxidation. Such effect is associated with suppression of
      autophagy regulators. 

PMID- 21720544
TI  - Statistical analyses support power law distributions found in neuronal
      avalanches.
AB  - The size distribution of neuronal avalanches in cortical networks has been
      reported to follow a power law distribution with exponent close to -1.5, which is
      a reflection of long-range spatial correlations in spontaneous neuronal activity.
      However, identifying power law scaling in empirical data can be difficult and
      sometimes controversial. In the present study, we tested the power law hypothesis
      for neuronal avalanches by using more stringent statistical analyses. In
      particular, we performed the following steps: (i) analysis of finite-size scaling
      to identify scale-free dynamics in neuronal avalanches, (ii) model parameter
      estimation to determine the specific exponent of the power law, and (iii)
      comparison of the power law to alternative model distributions. Consistent with
      critical state dynamics, avalanche size distributions exhibited robust scaling
      behavior in which the maximum avalanche size was limited only by the spatial
      extent of sampling ("finite size" effect). This scale-free dynamics suggests the
      power law as a model for the distribution of avalanche sizes. Using both the
      Kolmogorov-Smirnov statistic and a maximum likelihood approach, we found the
      slope to be close to -1.5, which is in line with previous reports. Finally, the
      power law model for neuronal avalanches was compared to the exponential and to
      various heavy-tail distributions based on the Kolmogorov-Smirnov distance and by
      using a log-likelihood ratio test. Both the power law distribution without and
      with exponential cut-off provided significantly better fits to the cluster size
      distributions in neuronal avalanches than the exponential, the lognormal and the
      gamma distribution. In summary, our findings strongly support the power law
      scaling in neuronal avalanches, providing further evidence for critical state
      dynamics in superficial layers of cortex.

PMID- 21720545
TI  - Structural and histone binding ability characterizations of human PWWP domains.
AB  - BACKGROUND: The PWWP domain was first identified as a structural motif of 100-130
      amino acids in the WHSC1 protein and predicted to be a protein-protein
      interaction domain. It belongs to the Tudor domain 'Royal Family', which consists
      of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT
      domains have long been known to bind methylated histones, PWWP was shown to
      exhibit histone binding ability only until recently. METHODOLOGY/PRINCIPAL
      FINDINGS: The PWWP domain has been shown to be a DNA binding domain, but sequence
      analysis and previous structural studies show that the PWWP domain exhibits
      significant similarity to other 'Royal Family' members, implying that the PWWP
      domain has the potential to bind histones. In order to further explore the
      function of the PWWP domain, we used the protein family approach to determine the
      crystal structures of the PWWP domains from seven different human proteins. Our
      fluorescence polarization binding studies show that PWWP domains have weak
      histone binding ability, which is also confirmed by our NMR titration
      experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP
      domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3
      and H4K20me3. CONCLUSIONS: PWWP proteins constitute a new family of methyl lysine
      histone binders. The PWWP domain consists of three motifs: a canonical beta
      barrel core, an insertion motif between the second and third beta-strands and a C
      terminal alpha-helix bundle. Both the canonical beta-barrel core and the
      insertion motif are directly involved in histone binding. The PWWP domain has
      been previously shown to be a DNA binding domain. Therefore, the PWWP domain
      exhibits dual functions: binding both DNA and methyllysine histones. ENHANCED
      VERSION: This article can also be viewed as an enhanced version in which the text
      of the article is integrated with interactive 3D representations and animated
      transitions. Please note that a web plugin is required to access this enhanced
      functionality. Instructions for the installation and use of the web plugin are
      available in Text S1.

PMID- 21720546
TI  - Comparative economic evaluation of Haemophilus influenzae type b vaccination in
      Belarus and Uzbekistan.
AB  - BACKGROUND: Hib vaccine has gradually been introduced into more and more
      countries during the past two decades, partly due to GAVI Alliance support to low
      income countries. However, since Hib disease burden is difficult to establish in
      settings with limited diagnostic capacities and since the vaccine continues to be
      relatively expensive, some Governments remain doubtful about its value leading to
      concerns about financial sustainability. Similarly, several middle-income
      countries have not introduced the vaccine. The aim of this study is to estimate
      and compare the cost-effectiveness of Hib vaccination in a country relying on
      self-financing (Belarus) and a country eligible for GAVI Alliance support
      (Uzbekistan). METHODS AND FINDINGS: A decision analytic model was used to
      estimate morbidity and mortality from Hib meningitis, Hib pneumonia and other
      types of Hib disease with and without the vaccine. Treatment costs were attached
      to each disease event. Data on disease incidence, case fatality ratios and costs
      were primarily determined from national sources. For the Belarus 2009 birth
      cohort, Hib vaccine is estimated to prevent 467 invasive disease cases, 4 cases
      of meningitis sequelae, and 3 deaths, while in Uzbekistan 3,069 invasive cases,
      34 sequelae cases and 341 deaths are prevented. Estimated costs per discounted
      DALY averted are US$ 9,323 in Belarus and US$ 267 in Uzbekistan. CONCLUSION: The
      primary reason why the cost-effectiveness values are more favourable in
      Uzbekistan than in Belarus is that relatively more deaths are averted in
      Uzbekistan due to higher baseline mortality burden. Two other explanations are
      that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three
      dose schedule compared to four doses in Belarus. However, when seen in the
      context of the relative ability to pay for public health, the vaccine can be
      considered cost-effective in both countries.

PMID- 21720547
TI  - Endothelial cell-specific molecule 2 (ECSM2) localizes to cell-cell junctions and
      modulates bFGF-directed cell migration via the ERK-FAK pathway.
AB  - BACKGROUND: Despite its first discovery by in silico cloning of novel endothelial
      cell-specific genes a decade ago, the biological functions of endothelial cell
      specific molecule 2 (ECSM2) have only recently begun to be understood. Limited
      data suggest its involvement in cell migration and apoptosis. However, the
      underlying signaling mechanisms and novel functions of ECSM2 remain to be
      explored. METHODOLOGY/PRINCIPAL FINDINGS: A rabbit anti-ECSM2 monoclonal antibody
      (RabMAb) was generated and used to characterize the endogenous ECSM2 protein.
      Immunoblotting, immunoprecipitation, deglycosylation, immunostaining and confocal
      microscopy validated that endogenous ECSM2 is a plasma membrane glycoprotein
      preferentially expressed in vascular endothelial cells (ECs). Expression patterns
      of heterologously expressed and endogenous ECSM2 identified that ECSM2 was
      particularly concentrated at cell-cell contacts. Cell aggregation and transwell
      assays showed that ECSM2 promoted cell-cell adhesion and attenuated basic
      fibroblast growth factor (bFGF)-driven EC migration. Gain or loss of function
      assays by overexpression or knockdown of ECSM2 in ECs demonstrated that ECSM2
      modulated bFGF-directed EC motility via the FGF receptor (FGFR)-extracellular
      regulated kinase (ERK)-focal adhesion kinase (FAK) pathway. The counterbalance
      between FAK tyrosine phosphorylation (activation) and ERK-dependent serine
      phosphorylation of FAK was critically involved. A model of how ECSM2 signals to
      impact bFGF/FGFR-driven EC migration was proposed. CONCLUSIONS/SIGNIFICANCE:
      ECSM2 is likely a novel EC junctional protein. It can promote cell-cell adhesion
      and inhibit bFGF-mediated cell migration. Mechanistically, ECSM2 attenuates EC
      motility through the FGFR-ERK-FAK pathway. The findings suggest that ECSM2 could
      be a key player in coordinating receptor tyrosine kinase (RTK)-, integrin-, and
      EC junctional component-mediated signaling and may have important implications in
      disorders related to endothelial dysfunction and impaired EC junction signaling.

PMID- 21720548
TI  - Blood cell telomere length is a dynamic feature.
AB  - There is a considerable heterogeneity in blood cell telomere length (TL) for
      individuals of similar age and recent studies have revealed that TL changes by
      time are dependent on TL at baseline. TL is partly inherited, but results from
      several studies indicate that e.g. life style and/or environmental factors can
      affect TL during life. Collectively, these studies imply that blood cell TL might
      fluctuate during a life time and that the actual TL at a defined time point is
      the result of potential regulatory mechanism(s) and environmental factors. We
      analyzed relative TL (RTL) in subsequent blood samples taken six months apart
      from 50 individuals and found significant associations between RTL changes and
      RTL at baseline. Individual RTL changes per month were more pronounced than the
      changes recorded in a previously studied population analyzed after 10 years'
      follow up. The data argues for an oscillating TL pattern which levels out at
      longer follow up times. In a separate group of five blood donors, a marked
      telomere loss was demonstrated within a six month period for one donor where
      after TL was stabilized. PCR determined RTL changes were verified by Southern
      blotting and STELA (single telomere elongation length analysis). The STELA
      demonstrated that for the donor with a marked telomere loss, the heterogeneity of
      the telomere distribution decreased considerably, with a noteworthy loss of the
      largest telomeres. In summary, the collected data support the concept that
      individual blood cell telomere length is a dynamic feature and this will be
      important to recognize in future studies of human telomere biology.

PMID- 21720549
TI  - Does the macaque monkey provide a good model for studying human executive
      control? A comparative behavioral study of task switching.
AB  - The ability to swiftly and smoothly switch from one task set to another is
      central to intelligent behavior, because it allows an organism to flexibly adapt
      to ever changing environmental conditions and internal needs. For this reason,
      researchers interested in executive control processes have often relied on task
      switching paradigms as powerful tools to uncover the underlying cognitive and
      brain architecture. In order to gather fundamental information at the single-cell
      level, it would be greatly helpful to demonstrate that non-human primates,
      especially the macaque monkey, share with us similar behavioral manifestations of
      task-switching and therefore, in all likelihood, similar underlying brain
      mechanisms. Unfortunately, prior attempts have provided negative results (e.g.,
      Stoet & Snyder, 2003b), in that it was reported that macaques do not show the
      typical signature of task-switching operations at the behavioral level,
      represented by switch costs. If confirmed, this would indicate that the macaque
      cannot be used as a model approach to explore human executive control mechanisms
      by means of task-switching paradigms. We have therefore decided to re-explore
      this issue, by conducting a comparative experiment on a group of human
      participants and two macaque monkeys, whereby we measured and compared
      performance costs linked to task switching and resistance to interference across
      the two species. Contrary to what previously reported, we found that both species
      display robust task switching costs, thus supporting the claim that macaque
      monkeys provide an exquisitely suitable model to study the brain mechanisms
      responsible for maintaining and switching task sets.

PMID- 21720550
TI  - Carcinoma matrix controls resistance to cisplatin through talin regulation of NF
      kB.
AB  - Extracellular matrix factors within the tumor microenvironment that control
      resistance to chemotherapeutics are poorly understood. This study focused on
      understanding matrix adhesion pathways that control the oral carcinoma response
      to cisplatin. Our studies revealed that adhesion of HN12 and JHU012 oral
      carcinomas to carcinoma matrix supported tumor cell proliferation in response to
      treatment with cisplatin. Proliferation in response to 30 uM cisplatin was not
      observed in HN12 cells adherent to other purified extracellular matrices such as
      Matrigel, collagen I, fibronectin or laminin I. Integrin beta1 was important for
      adhesion to carcinoma matrix to trigger proliferation after treatment with
      cisplatin. Disruption of talin expression in HN12 cells adherent to carcinoma
      matrix increased cisplatin induced proliferation. Pharmacological inhibitors were
      used to determine signaling events required for talin deficiency to regulate
      cisplatin induced proliferation. Pharmacological inhibition of NF-kB reduced
      proliferation of talin-deficient HN12 cells treated with 30 uM cisplatin. Nuclear
      NF-kB activity was assayed in HN12 cells using a luciferase reporter of NF-kB
      transcriptional activity. Nuclear NF-kB activity was similar in HN12 cells
      adherent to carcinoma matrix and collagen I when treated with vehicle DMSO.
      Following treatment with 30 uM cisplatin, NF-kB activity is maintained in cells
      adherent to carcinoma matrix whereas NF-kB activity is reduced in collagen I
      adherent cells. Expression of talin was sufficient to trigger proliferation of
      HN12 cells adherent to collagen I following treatment with 1 and 30 uM cisplatin.
      Talin overexpression was sufficient to trigger NF-kB activity following treatment
      with cisplatin in carcinoma matrix adherent HN12 cells in a process disrupted by
      FAK siRNA. Thus, adhesions within the carcinoma matrix create a matrix
      environment in which exposure to cisplatin induces proliferation through the
      function of integrin beta1, talin and FAK pathways that regulate NF-kB nuclear
      activity.

PMID- 21720551
TI  - Schwann-spheres derived from injured peripheral nerves in adult mice--their in
      vitro characterization and therapeutic potential.
AB  - Multipotent somatic stem cells have been identified in various adult tissues.
      However, the stem/progenitor cells of the peripheral nerves have been isolated
      only from fetal tissues. Here, we isolated Schwann-cell precursors/immature
      Schwann cells from the injured peripheral nerves of adult mice using a floating
      culture technique that we call "Schwann-spheres." The Schwann-spheres were
      derived from de-differentiated mature Schwann cells harvested 24 hours to 6 weeks
      after peripheral nerve injury. They had extensive self-renewal and
      differentiation capabilities. They strongly expressed the immature-Schwann-cell
      marker p75, and differentiated only into the Schwann-cell lineage. The spheres
      showed enhanced myelin formation and neurite growth compared to mature Schwann
      cells in vitro. Mature Schwann cells have been considered a promising candidate
      for cell-transplantation therapies to repair the damaged nervous system, whereas
      these "Schwann-spheres" would provide a more potential autologous cell source for
      such transplantation.

PMID- 21720552
TI  - New structural and functional contexts of the Dx[DN]xDG linear motif: insights
      into evolution of calcium-binding proteins.
AB  - Binding of calcium ions (Ca2+) to proteins can have profound effects on their
      structure and function. Common roles of calcium binding include structure
      stabilization and regulation of activity. It is known that diverse families--EF
      hands being one of at least twelve--use a Dx[DN]xDG linear motif to bind calcium
      in near-identical fashion. Here, four novel structural contexts for the motif are
      described. Existing experimental data for one of them, a thermophilic archaeal
      subtilisin, demonstrate for the first time a role for Dx[DN]xDG-bound calcium in
      protein folding. An integrin-like embedding of the motif in the blade of a beta
      propeller fold--here named the calcium blade--is discovered in structures of
      bacterial and fungal proteins. Furthermore, sensitive database searches suggest a
      common origin for the calcium blade in beta-propeller structures of different
      sizes and a pan-kingdom distribution of these proteins. Factors favouring the
      multiple convergent evolution of the motif appear to include its general Asp
      richness, the regular spacing of the Asp residues and the fact that change of Asp
      into Gly and vice versa can occur though a single nucleotide change. Among the
      known structural contexts for the Dx[DN]xDG motif, only the calcium blade and the
      EF-hand are currently found intracellularly in large numbers, perhaps because the
      higher extracellular concentration of Ca2+ allows for easier fixing of newly
      evolved motifs that have acquired useful functions. The analysis presented here
      will inform ongoing efforts toward prediction of similar calcium-binding motifs
      from sequence information alone.

PMID- 21720553
TI  - Prevalence of metabolic syndrome and risks of abnormal serum alanine
      aminotransferase in Hispanics: a population-based study.
AB  - AIM: Study the prevalence of metabolic syndrome (MS) and risk factors for and
      association with elevated alanine aminotransferase (ALT) as markers of hepatic
      injury in a large Hispanic health disparity cohort with high rates of obesity.
      METHODS: Analysis of data from a prospective cross-sectional population based
      study. From 2004-7, we randomly recruited 2000 community participants to the
      Cameron County Hispanic Cohort collecting extensive socioeconomic, clinical and
      laboratory data. We excluded 153 subjects due to critical missing data. Pearson
      chi-square tests and Student's t-tests were used for categorical and continuous
      variable analysis, respectively. Logistic regression analysis was performed to
      determine the risk factors for elevated ALT. RESULTS: The mean age of the cohort
      was 45 years and 67% were females. The majority of the cohort was either
      overweight (32.4%) or obese (50.7%). Almost half (43.7%) had MS and nearly one
      third diabetes. Elevated ALT level was more prevalent in males than females.
      Obesity was a strong risk for abnormal ALT in both genders. Hypertriglyceridemia,
      hypercholesterolemia and young age were risks for elevated ALT in males only,
      whereas increased fasting plasma glucose was associated with elevated ALT in
      females only. CONCLUSION: We identified high prevalence of MS and markers of
      liver injury in this large Mexican American cohort with gender differences in
      prevalence and risk factors, with younger males at greatest risk.

PMID- 21720554
TI  - Alanine racemase mutants of Burkholderia pseudomallei and Burkholderia mallei and
      use of alanine racemase as a non-antibiotic-based selectable marker.
AB  - Burkholderia pseudomallei and Burkholderia mallei are category B select agents
      and must be studied under BSL3 containment in the United States. They are
      typically resistant to multiple antibiotics, and the antibiotics used to treat B.
      pseudomallei or B. mallei infections may not be used as selective agents with the
      corresponding Burkholderia species. Here, we investigated alanine racemase
      deficient mutants of B. pseudomallei and B. mallei for development of non
      antibiotic-based genetic selection methods and for attenuation of virulence. The
      genome of B. pseudomallei K96243 has two annotated alanine racemase genes
      (bpsl2179 and bpss0711), and B. mallei ATCC 23344 has one (bma1575). Each of
      these genes encodes a functional enzyme that can complement the alanine racemase
      deficiency of Escherichia coli strain ALA1. Herein, we show that B. pseudomallei
      with in-frame deletions in both bpsl2179 and bpss0711, or B. mallei with an in
      frame deletion in bma1575, requires exogenous D-alanine for growth. Introduction
      of bpsl2179 on a multicopy plasmid into alanine racemase deficient variants of
      either Burkholderia species eliminated the requirement for D-alanine. During log
      phase growth without D-alanine, the viable counts of alanine racemase deficient
      mutants of B. pseudomallei and B. mallei decreased within 2 hours by about 1000
      fold and 10-fold, respectively, and no viable bacteria were present at 24 hours.
      We constructed several genetic tools with bpsl2179 as a selectable genetic
      marker, and we used them without any antibiotic selection to construct an in
      frame DeltaflgK mutant in the alanine racemase deficient variant of B.
      pseudomallei K96243. In murine peritoneal macrophages, wild type B. mallei ATCC
      23344 was killed much more rapidly than wild type B. pseudomallei K96243. In
      addition, the alanine racemase deficient mutant of B. pseudomallei K96243
      exhibited attenuation versus its isogenic parental strain with respect to growth
      and survival in murine peritoneal macrophages.

PMID- 21720555
TI  - Spindle assembly checkpoint regulates mitotic cell cycle progression during
      preimplantation embryo development.
AB  - Errors in chromosome segregation or distribution may result in aneuploid embryo
      formation, which causes implantation failure, spontaneous abortion, genetic
      diseases, or embryo death. Embryonic aneuploidy occurs when chromosome
      aberrations are present in gametes or early embryos. To date, it is still unclear
      whether the spindle assembly checkpoint (SAC) is required for the regulation of
      mitotic cell cycle progression to ensure mitotic fidelity during preimplantation
      development. In this study, using overexpression and RNA interference (RNAi)
      approaches, we analyzed the role of SAC components (Bub3, BubR1 and Mad2) in
      mouse preimplantation embryos. Our data showed that overexpressed SAC components
      inhibited metaphase-anaphase transition by preventing sister chromatid
      segregation. Deletion of SAC components by RNAi accelerated the metaphase
      anaphase transition during the first cleavage and caused micronuclei formation,
      chromosome misalignment and aneuploidy, which caused decreased implantation and
      delayed development. Furthermore, in the presence of the spindle-depolymerizing
      drug nocodazole, SAC depleted embryos failed to arrest at metaphase. Our results
      suggest that SAC is essential for the regulation of mitotic cell cycle
      progression in cleavage stage mouse embryos.

PMID- 21720556
TI  - Transgenic zebrafish recapitulating tbx16 gene early developmental expression.
AB  - We describe the creation of a transgenic zebrafish expressing GFP driven by a 7.5
      kb promoter region of the tbx16 gene. This promoter segment is sufficient to
      recapitulate early embryonic expression of endogenous tbx16 in the presomitic
      mesoderm, the polster and, subsequently, in the hatching gland. Expression of GFP
      in the transgenic lines later in development diverges to some extent from
      endogenous tbx16 expression with the serendipitous result that one line expresses
      GFP specifically in commissural primary ascending (CoPA) interneurons of the
      developing spinal cord. Using this line we demonstrate that the gene mafba
      (valentino) is expressed in CoPA interneurons.

PMID- 21720557
TI  - Transcriptome sequencing and de novo analysis for Yesso scallop (Patinopecten
      yessoensis) using 454 GS FLX.
AB  - BACKGROUND: Bivalves comprise 30,000 extant species, constituting the second
      largest group of mollusks. However, limited genetic research has focused on this
      group of animals so far, which is, in part, due to the lack of genomic resources.
      The advent of high-throughput sequencing technologies enables generation of
      genomic resources in a short time and at a minimal cost, and therefore provides a
      turning point for bivalve research. In the present study, we performed de novo
      transcriptome sequencing to first produce a comprehensive expressed sequence tag
      (EST) dataset for the Yesso scallop (Patinopecten yessoensis). RESULTS: In a
      single 454 sequencing run, 805,330 reads were produced and then assembled into
      32,590 contigs, with about six-fold sequencing coverage. A total of 25,237 unique
      protein-coding genes were identified from a variety of developmental stages and
      adult tissues based on sequence similarities with known proteins. As determined
      by GO annotation and KEGG pathway mapping, functional annotation of the unigenes
      recovered diverse biological functions and processes. Transcripts putatively
      involved in growth, reproduction and stress/immune-response were identified. More
      than 49,000 single nucleotide polymorphisms (SNPs) and 2,700 simple sequence
      repeats (SSRs) were also detected. CONCLUSION: Our data provide the most
      comprehensive transcriptomic resource currently available for P. yessoensis.
      Candidate genes potentially involved in growth, reproduction, and stress/immunity
      response were identified, and are worthy of further investigation. A large number
      of SNPs and SSRs were also identified and ready for marker development. This
      resource should lay an important foundation for future genetic or genomic studies
      on this species.

PMID- 21720558
TI  - Systemic BCG immunization induces persistent lung mucosal multifunctional CD4
      T(EM) cells which expand following virulent mycobacterial challenge.
AB  - To more closely understand the mechanisms of how BCG vaccination confers immunity
      would help to rationally design improved tuberculosis vaccines that are urgently
      required. Given the established central role of CD4 T cells in BCG induced
      immunity, we sought to characterise the generation of memory CD4 T cell responses
      to BCG vaccination and M. bovis infection in a murine challenge model. We
      demonstrate that a single systemic BCG vaccination induces distinct systemic and
      mucosal populations of T effector memory (T(EM)) cells in vaccinated mice. These
      CD4+CD44(hi)CD62L(lo)CD27- T cells concomitantly produce IFN-gamma and TNF-alpha,
      or IFN-gamma, IL-2 and TNF-alpha and have a higher cytokine median fluorescence
      intensity MFI or 'quality of response' than single cytokine producing cells.
      These cells are maintained for long periods (>16 months) in BCG protected mice,
      maintaining a vaccine-specific functionality. Following virulent mycobacterial
      challenge, these cells underwent significant expansion in the lungs and are,
      therefore, strongly associated with protection against M. bovis challenge. Our
      data demonstrate that a persistent mucosal population of T(EM) cells can be
      induced by parenteral immunization, a feature only previously associated with
      mucosal immunization routes; and that these multifunctional T(EM) cells are
      strongly associated with protection. We propose that these cells mediate
      protective immunity, and that vaccines designed to increase the number of
      relevant antigen-specific T(EM) in the lung may represent a new generation of TB
      vaccines.

PMID- 21720559
TI  - Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic
      effect of gemcitabine in human pancreatic cancer cells.
AB  - Survival rates for patients with pancreatic cancer are extremely poor due to its
      asymptomatic progression to advanced and metastatic stage for which current
      therapies remain largely ineffective. Therefore, novel therapeutic agents and
      treatment approaches are desired to improve the clinical outcome. In this study,
      we determined the effects of honokiol, a biologically active constituent of
      oriental medicinal herb Magnolia officinalis/grandiflora, on two pancreatic
      cancer cell lines, MiaPaCa and Panc1, alone and in combination with the standard
      chemotherapeutic drug, gemcitabine. Honokiol exerted growth inhibitory effects on
      both the pancreatic cancer cell lines by causing cell cycle arrest at G1 phase
      and induction of apoptosis. At the molecular level, honokiol markedly decreased
      the expression of cyclins (D1 and E) and cyclin-dependent kinases (Cdk2 and
      Cdk4), and caused an increase in Cdk inhibitors, p21 and p27. Furthermore,
      honokiol treatment led to augmentation of Bax/Bcl-2 and Bax/Bcl-xL ratios to
      favor apoptosis in pancreatic cancer cells. These changes were accompanied by
      enhanced cytoplasmic accumulation of NF-kappaB with a concomitant decrease in
      nuclear fraction and reduced transcriptional activity of NF-kappaB responsive
      promoter. This was associated with decreased phosphorylation of inhibitor of
      kappa B alpha (IkappaB-alpha) causing its stabilization and thus increased
      cellular levels. Importantly, honokiol also potentiated the cytotoxic effects of
      gemcitabine, in part, by restricting the gemcitabine-induced nuclear accumulation
      of NF-kappaB in the treated pancreatic cancer cell lines. Altogether, these
      findings demonstrate, for the first time, the growth inhibitory effects of
      honokiol in pancreatic cancer and indicate its potential usefulness as a novel
      natural agent in prevention and therapy.

PMID- 21720560
TI  - Computational study of hippocampal-septal theta rhythm changes due to beta
      amyloid-altered ionic channels.
AB  - Electroencephagraphy (EEG) of many dementia patients has been characterized by an
      increase in low frequency field potential oscillations. One of the
      characteristics of early stage Alzheimer's disease (AD) is an increase in theta
      band power (4-7 Hz). However, the mechanism(s) underlying the changes in theta
      oscillations are still unclear. To address this issue, we investigate the theta
      band power changes associated with beta-Amyloid (Abeta) peptide (one of the main
      markers of AD) using a computational model, and by mediating the toxicity of
      hippocampal pyramidal neurons. We use an established biophysical hippocampal CA1
      medial septum network model to evaluate four ionic channels in pyramidal neurons,
      which were demonstrated to be affected by Abeta. They are the L-type Ca2+
      channel, delayed rectifying K+ channel, A-type fast-inactivating K+ channel and
      large-conductance Ca2+-activated K+ channel. Our simulation results demonstrate
      that only the Abeta inhibited A-type fast-inactivating K+ channel can induce an
      increase in hippocampo-septal theta band power, while the other channels do not
      affect theta rhythm. We further deduce that this increased theta band power is
      due to enhanced synchrony of the pyramidal neurons. Our research may elucidate
      potential biomarkers and therapeutics for AD. Further investigation will be
      helpful for better understanding of AD-induced theta rhythm abnormalities and
      associated cognitive deficits.

PMID- 21720561
TI  - Determinants of sensitivity to DZNep induced apoptosis in multiple myeloma cells.
AB  - The 3-Deazaneplanocin A (DZNep), one of S-adenosylhomocysteine (AdoHcy) hydrolase
      inhibitors, has shown antitumor activities in a broad range of solid tumors and
      acute myeloid leukemia. Here, we examined its effects on multiple myeloma (MM)
      cells and found that, at 500 nM, it potently inhibited growth and induced
      apoptosis in 2 of 8 MM cell lines. RNA from un-treated and DZNep treated cells
      was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a
      significant change in gene expression were determined by significance analysis of
      microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in
      sensitive cells and was expressed at low level in resistant cells. The results
      were corroborated by quantitative RT-PCR. Western-blot analysis indicated ALOX5
      was highly expressed only in sensitive cell line H929 and greatly decreased upon
      DZNep treatment. Ectopic expression of ALOX5 reduced sensitivity to DZNep in H929
      cells. Furthermore, down-regulation of ALOX5 by RNA interference could also
      induce apoptosis in H929. Gene expression analysis on MM patient dataset
      indicated ALOX5 expression was significantly higher in MM patients compared to
      normal plasma cells. We also found that Bcl-2 was overexpressed in DZNep
      insensitive cells, and cotreatment with DZNep and ABT-737, a Bcl-2 family
      inhibitor, synergistically inhibited growth and induced apoptosis of DZNep
      insensitive MM cells. Taken together, this study shows one of mechanisms of the
      DZNep efficacy on MM correlates with its ability to down-regulate the ALOX5
      levels. In addition, DZNep insensitivity might be associated with overexpression
      of Bcl-2, and the combination of ABT-737 and DZNep could synergistically induced
      apoptosis. These results suggest that DZNep may be exploited therapeutically for
      a subset of MM.

PMID- 21720562
TI  - Emotional facial expression detection in the peripheral visual field.
AB  - BACKGROUND: In everyday life, signals of danger, such as aversive facial
      expressions, usually appear in the peripheral visual field. Although facial
      expression processing in central vision has been extensively studied, this
      processing in peripheral vision has been poorly studied. METHODOLOGY/PRINCIPAL
      FINDINGS: Using behavioral measures, we explored the human ability to detect fear
      and disgust vs. neutral expressions and compared it to the ability to
      discriminate between genders at eccentricities up to 40 degrees . Responses were
      faster for the detection of emotion compared to gender. Emotion was detected from
      fearful faces up to 40 degrees  of eccentricity. CONCLUSIONS: Our results
      demonstrate the human ability to detect facial expressions presented in the far
      periphery up to 40 degrees  of eccentricity. The increasing advantage of emotion
      compared to gender processing with increasing eccentricity might reflect a major
      implication of the magnocellular visual pathway in facial expression processing.
      This advantage may suggest that emotion detection, relative to gender
      identification, is less impacted by visual acuity and within-face crowding in the
      periphery. These results are consistent with specific and automatic processing of
      danger-related information, which may drive attention to those messages and allow
      for a fast behavioral reaction.

PMID- 21720563
TI  - Phenotypic expression of ADAMTS13 in glomerular endothelial cells.
AB  - BACKGROUND: ADAMTS13 is the physiological von Willebrand factor (VWF)-cleaving
      protease. The aim of this study was to examine ADAMTS13 expression in kidneys
      from ADAMTS13 wild-type (Adamts13+/+) and deficient (Adamts13-/-) mice and to
      investigate the expression pattern and bioactivity in human glomerular
      endothelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemistry was
      performed on kidney sections from ADAMTS13 wild-type and ADAMTS13-deficient mice.
      Phenotypic differences were examined by ultramorphology. ADAMTS13 expression in
      human glomerular endothelial cells and dermal microvascular endothelial cells was
      investigated by real-time PCR, flow cytometry, immunofluorescence and
      immunoblotting. VWF cleavage was demonstrated by multimer structure analysis and
      immunoblotting. ADAMTS13 was demonstrated in glomerular endothelial cells in
      Adamts13+/+ mice but no staining was visible in tissue from Adamts13-/- mice.
      Thickening of glomerular capillaries with platelet deposition on the vessel wall
      was detected in Adamts13-/- mice. ADAMTS13 mRNA and protein were detected in both
      human endothelial cells and the protease was secreted. ADAMTS13 activity was
      demonstrated in glomerular endothelial cells as cleavage of VWF.
      CONCLUSIONS/SIGNIFICANCE: Glomerular endothelial cells express and secrete
      ADAMTS13. The proteolytic activity could have a protective effect preventing
      deposition of platelets along capillary lumina under the conditions of high shear
      stress present in glomerular capillaries.

PMID- 21720564
TI  - Wave-of-advance models of the diffusion of the Y chromosome haplogroup R1b1b2 in
      Europe.
AB  - Whether or not the spread of agriculture in Europe was accompanied by movements
      of people is a long-standing question in archeology and anthropology, which has
      been frequently addressed with the help of population genetic data. Estimates on
      dates of expansion and geographic origins obtained from genetic data are however
      sensitive to the calibration of mutation rates and to the mathematical models
      used to perform inference. For instance, recent data on the Y chromosome
      haplogroup R1b1b2 (M269) have either suggested a Neolithic origin for European
      paternal lineages or a more ancient Paleolithic origin depending on the
      calibration of Y-STR mutation rates. Here we examine the date of expansion and
      the geographic origin of hgR1b1b2 considering two current estimates of mutation
      rates in a total of fourteen realistic wave-of-advance models. We report that a
      range expansion dating to the Paleolithic is unlikely to explain the observed
      geographical distribution of microsatellite diversity, and that whether the data
      is informative with respect to the spread of agriculture in Europe depends on the
      mutation rate assumption in a critical way.

PMID- 21720565
TI  - Soluble CD59 expressed from an adenovirus in vivo is a potent inhibitor of
      complement deposition on murine liver vascular endothelium.
AB  - Inappropriate activation of complement on the vascular endothelium of specific
      organs, or systemically, underlies the etiology of a number of diseases. These
      disorders include atypical hemolytic uremic syndrome, membranoproliferative
      glomerulonephritis, atherosclerosis, age-related macular degeneration, diabetic
      retinopathy, and transplant rejection. Inhibition of the terminal step of
      complement activation, i.e. formation of the membrane attack complex, using CD59
      has the advantage of retaining the upstream processes of the complement cascade
      necessary for fighting pathogens and retaining complement's crucial role in
      tissue homeostasis. Previous studies have shown the necessity of membrane
      targeting of soluble CD59 in order for it to prove an effective inhibitor of
      complement deposition both in vitro and in vivo. In this study we have generated
      an in vivo model of human complement activation on murine liver vascular
      endothelium. This model should prove useful for the development of anti
      complement therapies for complement-induced pathologies of vascular endothelium.
      Using this model, we have demonstrated the viability of a non membrane-targeted
      soluble CD59 to significantly inhibit complement deposition on the endothelium of
      murine liver vasculature when expressed in vivo from an adenovirus. This result,
      unanticipated based on prior studies, suggests that the use of non membrane
      targeted sCD59 as an anti-complement therapy be re-visited.

PMID- 21720566
TI  - Stabilizing salt-bridge enhances protein thermostability by reducing the heat
      capacity change of unfolding.
AB  - Most thermophilic proteins tend to have more salt bridges, and achieve higher
      thermostability by up-shifting and broadening their protein stability curves.
      While the stabilizing effect of salt-bridge has been extensively studied,
      experimental data on how salt-bridge influences protein stability curves are
      scarce. Here, we used double mutant cycles to determine the temperature
      dependency of the pair-wise interaction energy and the contribution of salt
      bridges to DeltaC(p) in a thermophilic ribosomal protein L30e. Our results showed
      that the pair-wise interaction energies for the salt-bridges E6/R92 and E62/K46
      were stabilizing and insensitive to temperature changes from 298 to 348 K. On the
      other hand, the pair-wise interaction energies between the control long-range ion
      pair of E90/R92 were negligible. The DeltaC(p) of all single and double mutants
      were determined by Gibbs-Helmholtz and Kirchhoff analyses. We showed that the two
      stabilizing salt-bridges contributed to a reduction of DeltaC(p) by 0.8-1.0 kJ
      mol-1 K-1. Taken together, our results suggest that the extra salt-bridges found
      in thermophilic proteins enhance the thermostability of proteins by reducing
      DeltaC(p), leading to the up-shifting and broadening of the protein stability
      curves.

PMID- 21720567
TI  - Preschool Matters: Predicting Reading Difficulties for Spanish-Speaking Bilingual
      Students in First Grade.
AB  - This article reports on a longitudinal analysis of factors that predict the word
      reading skills in English and Spanish for a sample of 234 Spanish-speaking
      students in first grade. The children were assessed at the end of preschool,
      kindergarten, and first grade. Data include three subtests of the Woodcock
      Language Proficiency Battery and a researcher-developed phonological awareness
      task. Results showed that, on average, children's English word reading skills
      were similar to those of monolingual norms, while their Spanish word readings
      skills were, on average, one standard deviation below the mean. English
      vocabulary, English recalling skills, Spanish vocabulary, and Spanish word
      reading skills in preschool were found to be significant predictors of English
      word reading skills in first grade. Educational implications for assessment and
      instruction for this population during the early childhood years are discussed.

PMID- 21720568
TI  - Itch: Cells, Molecules, and Circuits.
AB  - The itch field has made great advances in recent years, building upon earlier
      work to form a clearer picture of the biology behind this important sensory
      modality. Models for how itch is encoded have emerged that fit with
      physiological, molecular, and behavioral data. The molecular mechanisms of itch,
      both peripherally and centrally, are being revealed with the aid of newer animal
      models. Future work must address shortcomings in our current understanding of
      itch including limitations of current experimental methods. Here we review what
      is known about the cells, molecules, and circuits involved in itch and highlight
      key questions that remain to be answered.

PMID- 21720569
TI  - Statistical models for predicting number of involved nodes in breast cancer
      patients.
AB  - Clinicians need to predict the number of involved nodes in breast cancer patients
      in order to ascertain severity, prognosis, and design subsequent treatment. The
      distribution of involved nodes often displays over-dispersion-a larger
      variability than expected. Until now, the negative binomial model has been used
      to describe this distribution assuming that over-dispersion is only due to
      unobserved heterogeneity. The distribution of involved nodes contains a large
      proportion of excess zeros (negative nodes), which can lead to over-dispersion.
      In this situation, alternative models may better account for over-dispersion due
      to excess zeros. This study examines data from 1152 patients who underwent
      axillary dissections in a tertiary hospital in India during January 1993-January
      2005. We fit and compare various count models to test model abilities to predict
      the number of involved nodes. We also argue for using zero inflated models in
      such populations where all the excess zeros come from those who have at some risk
      of the outcome of interest. The negative binomial regression model fits the data
      better than the Poisson, zero hurdle/inflated Poisson regression models. However,
      zero hurdle/inflated negative binomial regression models predicted the number of
      involved nodes much more accurately than the negative binomial model. This
      suggests that the number of involved nodes displays excess variability not only
      due to unobserved heterogeneity but also due to excess negative nodes in the data
      set. In this analysis, only skin changes and primary site were associated with
      negative nodes whereas parity, skin changes, primary site and size of tumor were
      associated with a greater number of involved nodes. In case of near equal
      performances, the zero inflated negative binomial model should be preferred over
      the hurdle model in describing the nodal frequency because it provides an
      estimate of negative nodes that are at "high-risk" of nodal involvement.

PMID- 21720570
TI  - Management of Corneal Graft Rejection - A Case Series Report and Review of the
      Literature.
AB  - PURPOSE: To report long-term results in a case series of patients treated with
      systemic immune suppression for prevention of penetrating keratoplasty (PKP)
      graft rejection. DESIGN: Retrospective noncomparative chart review. PARTICIPANTS:
      Three patients presented with PKP graft failure. METHODS: Patients received oral
      prednisone, azathioprine and cyclosporine to prevent rejection of repeat corneal
      transplant. Patients received repeat PKP and graft outcome was reported. MAIN
      OUTCOME MEASURES: Visual acuity and graft survival were recorded. RESULTS: Mean
      age was 55 years, two male and one female. Mean follow-up period was 37 months
      (range 24-46). All three patients completed the treatment protocol with minimal
      adverse effects. All grafts remained clear over observational period. CONCLUSION:
      Our study suggests that systemic immune suppression with 2 or more agents may be
      helpful to prevent corneal graft rejection in high-risk patients.

PMID- 21720571
TI  - Development of a Comprehensive Heart Disease Knowledge Questionnaire.
AB  - BACKGROUND: Heart disease is the number one killer of both men and women in the
      United States, yet a comprehensive and evidence-based heart disease knowledge
      assessment is currently not available.  PURPOSE: This paper describes the 2 phase
      development of a novel heart disease knowledge questionnaire.  METHODS: After
      review and critique of the existing literature, a questionnaire addressing 5
      central domains of heart disease knowledge was constructed. In Phase I, 606
      undergraduates completed a 82-item questionnaire. In Phase II, 248 undergraduates
      completed a revised 74-item questionnaire. In both phases, item clarity and
      difficulty were evaluated, along with the overall factor structure of the scale. 
      RESULTS: Exploratory and confirmatory factor analyses were used to reduce the
      scale to 30 items with fit statistics, CFI = .82, TLI = .88, and RMSEA = .03.
      Scores were correlated moderately positively with an existing scale and weakly
      positively with a measure of health literacy, thereby establishing both
      convergent and divergent validity.  DISCUSSION: The finalized 30-item
      questionnaire is a concise, yet discriminating instrument that reliably measures
      participants' heart disease knowledge levels.  TRANSLATION TO HEALTH EDUCATION
      PRACTICE: Health professionals can use this scale to assess their patients' heart
      disease knowledge so that they can create a tailored program to help their
      patients reduce their heart disease risk.

PMID- 21720572
TI  - The decline of medical innovation in the United States.

PMID- 21720573
TI  - Knot security, loop security, and elongation of braided polyblend sutures used
      for arthroscopic knots.
AB  - In the study described here, we evaluated load to failure and cyclic loading
      elongation of different braided polyblend sutures under different sliding knot
      configurations. Four braided polyblend sutures (FiberWire, Herculine, Orthocord,
      Ultrabraid) were tied with 5 sliding arthroscopic knots (Static surgeon, Weston,
      Roeder, Nicky, Tennessee slider) with a series of 3 reversing half-hitches on
      alternating posts (RHAPs). Each knot was tied around a 30-mm circumference post
      to ensure a consistent loop circumference. Loop security was measured as load to
      failure (load at 3-mm cross-head displacement or suture breakage) and loop
      elongation at a frequency of 1 Hz from 6 N to 30 N for 1000 cycles. Twenty knots
      were tied for each possible combination of knots and sutures, 10 for load to
      failure and 10 for cyclic loading test. For any given knot type, tying with
      Ultrabraid suture material resulted in maximum performance in the maximum load-to
      failure test. Conversely, tying with Orthocord resulted in a significantly lower
      maximum load to failure, with the exception of the Surgeon knot. The Weston knot
      with 3 RHAPs using Ultrabraid provided the highest load to failure(mean, 346 N;
      SD, 24 N). All knots elongated less than 0.45 mm at the 1000th cycle and
      experienced higher suture slippage at initial cyclic loading (50th cycles). At
      higher cycles, FiberWire and Orthocord demonstrated less than half of the suture
      slippage of Herculine and Ultrabraid (5x10(-5) vs 11x10(-5) mm/cycle). Different
      braided polyblend sutures provide different knot and loop security for a given
      type of sliding knot. All knots in this study appear to be durable with respect
      to resistance to loosening under cyclic loading conditions. The Weston knot with
      3 RHAPs using Ultrabraid provided the best loop and knot security. Our study
      results help further our understanding of the biomechanics of knot and loop
      security differences for different braided polyblend sutures.

PMID- 21720574
TI  - Incorporating evidence-based medicine in arthroscopic knot preferences: a survey
      of american orthopaedic society for sports medicine members.
AB  - An Internet-based survey was used to determine arthroscopic knot preferences.
      Inclusion criteria included American Orthopaedic Society for Sports Medicine
      (AOSSM) membership, and exclusion criteria included physician members without an
      e-mail address and nonphysician members. Our hypotheses were that the majority of
      arthroscopic knots used in clinical practice by AOSSM members are described in
      the orthopedic literature and have undergone biomechanical analysis, that the
      majority of members reinforced sliding arthroscopic knots with 3 reversed half
      hitches on alternating posts (RHAPs), and that the majority of members used a
      half-hitch configuration that incorporates at least 3 reversed half-hitches and 3
      alternating posts. Of the 1844 members contacted, 937 (50.8%) agreed to
      participate in the survey. The most common arthroscopic sliding knot used was the
      Duncan loop. Only 48.1% of respondents used 3 reversed half-hitches and at least
      3 alternating posts when using nonsliding knots. Only 31% of respondents used 3
      RHAPs to reinforce arthroscopic sliding knots. Only a minority of respondents
      used the optimal configuration determined in vitro for sliding knot reinforcement
      and when using a nonsliding half-hitch knot configuration. An evidence-based
      approach is recommended for determining arthroscopic knot preference for clinical
      use.

PMID- 21720575
TI  - Patellar metastatic melanoma in a 13-year-old boy.
AB  - The incidence of melanoma in US adults is approximately 1.5 per million, with 2%
      to 5% of patients developing metastatic disease. In children, melanoma is
      distinctly uncommon, and metastatic disease occurs even more seldom. This case
      report, the first of a patellar lesion as the initial presentation of metastatic
      melanoma in a pediatric patient, highlights use of patellectomy and
      intraoperative radiation therapy in obtaining palliative local control while
      avoiding periarticular functional morbidity.

PMID- 21720576
TI  - Isolated popliteus muscle rupture with neurovascular compression requiring
      surgical decompression.

PMID- 21720577
TI  - Outcomes of arthroscopic versus open rotator cuff repair: a systematic review of
      the literature.
AB  - Full-thickness rotator cuff tears are common. When symptomatic, they can affect
      quality of life. Surgical repair might improve patients' overall health. We
      systematically reviewed postoperative outcomes in 10 studies comparing mini-open
      repair and all-arthroscopic repair techniques. Data regarding patient
      demographics, rotator cuff pathology, postoperative rehabilitation protocols,
      American Shoulder and Elbow Surgeons (ASES) scores, University of California Los
      Angeles (UCLA) scores, pain scores, and incidence of recurrent defects were
      extracted. There were no statistically significant differences between groups
      within each study in terms of these data points. One study found decreased pain 6
      months after surgery in the all-arthroscopic group versus the miniopen repair
      group. This systematic literature review indicates there is no statistically
      significant difference in postoperative ASES, UCLA, or pain scores or incidence
      of recurrent rotator cuff tears in rotator cuffs repaired all-arthroscopically
      versus using the mini-open technique. However, there might be decreased short
      term pain in patients who undergo arthroscopic repairs.

PMID- 21720578
TI  - The effect of lordosis, disc height change, subsidence, and transitional segment
      on stand-alone anterior lumbar interbody fusion using a nontapered threaded
      device.
AB  - In this study, we retrospectively evaluated 37 consecutive patients who underwent
      stand-alone anterior lumbar interbody fusion (ALIF); for indications that
      included degenerative disc disease, concordant pain on discography, disc space
      collapse of more than 50%, and failure of nonoperative management for at least 4
      consecutive months. Patient demographics, procedural data, and prospective Short
      Form 36 General Health Survey composite scores were collected. Mean follow-up was
      24.2 months. In this cohort of patients with degenerative disc disease, there was
      no loosening or migration of implants. Stand-alone ALIF using a threaded
      interbody fusion device provided excellent clinical results and return-to-work
      rates with few complications. Increased lordosis was associated with increased
      subsidence and less favorable outcome. Patients with a transitional segment
      displayed relatively smaller increases in lordosis and better outcomes than
      patients without a transitional segment.

PMID- 21720579
TI  - Minimizing blood loss in major spinal surgery: a review of the current
      literature.

PMID- 21720580
TI  - ACGME accreditation and national health care reform.

PMID- 21720581
TI  - Early assessment of a new integrated preclinical musculoskeletal curriculum at a
      medical school.
AB  - Increased incidence of musculoskeletal conditions and medical students'
      deficiencies in musculoskeletal knowledge have been a cause for concern for
      educators in this field. Findings from a 2005 study conducted at our institution
      revealed that medical students, despite acknowledging the importance of
      musculoskeletal education, have inadequate knowledge and skill in this system. In
      response to these findings, additions to the preclinical musculoskeletal
      curriculum were designed and instituted. Medical students were assessed at the
      end of the new curriculum, using the same evaluation tools that had been
      administered before the curricular changes, and responses from the second-year
      students who completed the entire new preclinical curriculum were compared with
      those of students who had completed the old curriculum. Results showed that
      students reported significantly higher levels of clinical confidence in
      performing physical examinations of several anatomical regions of the
      musculoskeletal system. A notable proportion of students cited weaknesses in
      other fields, such as anatomy, as a prominent contributor to their lack of
      confidence in the musculoskeletal system.

PMID- 21720582
TI  - The effect of hospital setting and teaching status on outcomes after hip
      fracture.
AB  - This study used the National Inpatient Sample database for 1998 through 2003 to
      identify patients who were aged 65 years or older and had undergone surgical
      treatment for an isolated femoral neck or intertrochanteric hip fracture.
      Hospital setting (urban vs rural) and teaching status (teaching vs nonteaching)
      were the primary independent variables studied. The final cohort consisted of
      226,239 patients. Overall in-hospital mortality was 2.6%. Higher in-hospital
      mortality risk was associated with increased number of in-hospital complications,
      increased number of comorbidities, male sex, longer surgical delay, and age 85
      years or older. The overall surgical complication rate was 10.1%; there was
      little effect for any of the studied factors on risk for in-hospital
      complication. Contrary to expectation, hospital setting and teaching status were
      generally not as relevant to in-hospital outcomes as other factors were.

PMID- 21720583
TI  - Knee extensor function before and 1 year after simultaneous bilateral total knee
      arthroplasty: is there asymmetry between limbs?
AB  - One year after unilateral total knee arthroplasty (TKA), there is interlimb knee
      extensor function asymmetry. In the study reported here, we investigated whether
      there was knee extensor function "asymmetry" between limbs 1 year after
      simultaneous bilateral TKA. Fourteen patients volunteered to participate in this
      study before undergoing simultaneous bilateral TKA secondary to knee
      osteoarthritis. One year after surgery, 8 patients agreed to participate in
      follow-up testing. Torque production, work, and range of motion of knee extensors
      were assessed isokinetically at 1.047 radians . second(-1). Before surgery, there
      was no difference between limbs in peak torque, work, or range of motion during
      isokinetic testing. One year after surgery, this pattern persisted. The strength
      asymmetry evident in patients 1 year after unilateral TKA did not exist in
      patients who underwent simultaneous bilateral TKA. There is a symmetrical pattern
      between limbs for knee extensor function 1 year after the bilateral procedure.

PMID- 21720584
TI  - Metacarpal coccidioidal osteomyelitis.

PMID- 21720585
TI  - Chondrosarcoma of the foot.
AB  - Chondrosarcoma is a rare malignant cartilaginous tumor of the bone. It commonly
      occurs in the pelvis, proximal femur, and shoulder girdle. We present a case of a
      woman in her mid-50s with chondrosarcoma of the foot--a rare lesion that accounts
      for 0.5% to 2.97% of all chondrosarcomas. Distinguishing a chondrosarcoma of the
      foot from an enchondroma can prove difficult because of the greater cellularity
      and atypia that is allowable for enchondromas of the foot compared with those of
      other sites. There must be a combined clinical, radiographic, and histologic
      diagnosis. Treatment for chondrosarcoma is generally wide surgical excision.
      Chemotherapy or traditional radiation is not effective for most of these lesions.

PMID- 21720586
TI  - Incidence and variance of foot and ankle injuries in elite college football
      players.
AB  - We conducted a study on the risk for foot and ankle injuries in college football
      players on the basis of injury type and player position. In February 2006, we
      evaluated 320 intercollegiate football players at the National Football League
      Combine. All pathologic conditions and surgical procedures of the foot and ankle
      were recorded, and data were analyzed by player position to detect any trends.
      Seventy-two percent (n = 231) of the players had a history of foot and ankle
      injuries, with a total of 287 foot and ankle injuries (1.24 injuries/player
      injured). The most common injuries were lateral ankle sprain (n = 115),
      syndesmotic sprain (50), metatarsophalangeal dislocation/turf toe (36), and
      fibular fracture (25). Foot and ankle injuries were most common in
      kickers/punters (100% incidence), special teams (100%), running backs (83%), wide
      receivers (83%), and offensive linemen (80%). Lateral ankle sprains, the most
      common injuries, were treated surgically only 2.6% of the time. Offensive linemen
      were most likely to have had syndesmotic sprains (32%), and quarterbacks had the
      highest incidence of fibular fractures (16%). Foot and ankle injuries are common
      in collegiate football players, affecting 72% of players. Thirteen percent
      underwent surgical treatment. Trends are seen in the types of injuries for the
      different player positions.

PMID- 21720587
TI  - Greater trochanteric osteoplasty in revision hip arthroplasty: two case reports.
AB  - Proximal migration of the greater trochanter can make revision hip arthroplasty
      challenging, particularly in regard to surgically exposing the joint,
      establishing leg length, avoiding postoperative impingement and instability, and
      achieving a functional hip with less pain and more motion. Often, the surgical
      solution to these problems includes greater trochanteric and/or subtrochanteric
      osteotomy. In this report, we describe 2 cases treated with greater trochanteric
      osteoplasty (reshaping and partially resecting the greater trochanteric tip)
      through a modified direct lateral approach. This novel alternative surgical
      technique accomplishes the procedural goals without major osteotomy and its
      potential associated complications. The patients were very satisfied with their
      outcomes.

PMID- 21720588
TI  - Treatment options for symptomatic degenerative joint disease secondary to Legg
      Calve-Perthes disease.
AB  - The treatment options for neglected Legg-Calve-Perthes disease (LCPD) leading to
      symptomatic degenerative joint disease always have posed a challenge for the
      orthopedic surgeon. In addition, the literature is disorganized in this regard.
      Therefore, a structured literature review of the treatment options for the
      symptomatic sequelae of LCPD, especially in the context of joint replacement and
      resurfacing, is very much needed.

PMID- 21720589
TI  - Nonunion of a pertrochanteric femur fracture due to a low-velocity gunshot.
AB  - The treatment of nonunions often can be a complex and challenging venture. This
      case report details the treatment of a young patient's pertrochanteric femoral
      nonunion due to a low-velocity gunshot. Fracture fixation and union were
      attempted with various implants, including a sliding hip screw, blade plate, and
      proximal femoral locking plate; however, all eventually failed. Successful union
      ultimately was obtained only after use of a cephalomedullary nail. There have
      been few reports in the literature on the failure of proximal femoral locking
      plates in the treatment of pertrochanteric femur fractures, though much has been
      published regarding the sliding hip screw and blade plate. Multiple options for
      use in nonunion surgery were used and discussed in this case, such as autogenous
      bone graft, bone morphogenic protein, and implantable bone stimulators.

PMID- 21720590
TI  - Biomechanical evaluation of locking plate fixation with hybrid screw constructs
      in analogue humeri.
AB  - Locking plates are well suited to complex fracture patterns and weak bone. In the
      study reported here, we compared the structural stability of 3 different locking
      compression plate (LCP) constructs using composite analogue humeri. Eighteen
      analogue composite humeri were used as bone models. A 6.5-mm osteotomy gap was
      stabalized with a 9-hole 3.5-mm narrow LCP using four 3.5-mm self-tapping screws
      on each side of the fracture with the middle hole empty. Three construct
      configurations were studied: B (all screws bicortical), BU (bicortical screw on
      each side of fracture gap and remaining screws unicortal), and U (all screws
      unicortal). Each bone model was fixed in a customized jig and subjected to
      mediolateral and anteroposterior 4-point bending and external rotational torque
      to assess rigidity, stiffness, and failure. There was significant (P<.05)
      differences in torsional stiffness but no significant differences in terms of
      flexural rigidity between each of the constructs. The results also indicated that
      construct BU provided as much stability as the other constructs. Therefore,
      consideration should be given to type of fixation construct, especially when
      torsional stability is required. Replacing a single set of unicortal locking
      screws with bicortical locking screws closer to the fracture site improved
      construct stability compared with any unicortal screw construct. A hybrid
      fixation construct that provides bicortical screws at any location may provide
      equivalent construct stability in this model. Hybrid fixation constructs may
      provide adequate fracture stabilization for a fracture pattern that would
      typically be considered unstable.

PMID- 21720591
TI  - The American Journal of Orthopedics turns 40.

PMID- 21720592
TI  - Comparison of functional outcomes of total elbow arthroplasty vs plate fixation
      for distal humerus fractures in osteoporotic elbows.
AB  - Treating intra-articular fractures about the osteoporotic distal humerus poses a
      significant challenge. The purpose of this retrospective study was to evaluate
      functional outcomes for distal humeral fractures treated with total elbow
      arthroplasty (TEA) or open reduction and internal fixation (ORIF) in a
      nonarthritic elderly population with osteoporosis. We reviewed the records of all
      women older than age 60 who had undergone surgical treatment for intraarticular
      distal humerus fractures (Orthopaedic Trauma Association types 13B and 13C) by 1
      of 2 surgeons. Demographic and operative data were obtained, charts were
      reviewed, and patients were asked to have their outcomes evaluated with the
      Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the Mayo
      Elbow Performance Index (MEPI). Twenty-two patients (23 elbows) were identified,
      and 2 of these (3 elbows) were excluded. Of the remaining 20 patients, 9 had
      undergone cemented, semiconstrained TEA as initial treatment, and 11 had
      undergone ORIF. These 2 groups were compared. Mean follow-up was 14.8 months
      (range, 6-38 months). There were no significant differences between the TEA and
      ORIF groups with respect to demographic factors. Final elbow range of motion was
      92 degrees  flexion-extension arc (arthroplasty group) and 98 degrees  (fixation
      group). Two patients in the arthroplasty group and 2 in the fixation group died.
      For the remaining patients, mean DASH scores were 30.2 (arthroplasty) and 32.1
      (fixation), and mean MEPI scores were 79 (arthroplasty) and 85 (fixation). These
      differences were not statistically significant. Four TEAs developed radiographic
      loosening by a mean of 15 months, and 1 of these underwent revision with good
      outcome. Ten of the 11 fractures in the fixation group healed radiographically;
      the 1 nonunion with collapse continued to be asymptomatic. Two patients in the
      fixation group underwent contracture release after union for limited elbow range
      of motion. Many factors come into play in the treatment of intra-articular distal
      humerus fractures in patients with osteoporosis. Implant selection must be based
      on bone quality, expected outcome, and surgeon experience. For these injuries,
      good outcomes may be obtained with either TEA or ORIF.

PMID- 21720593
TI  - Talar neck fractures treated with closed reduction and percutaneous screw
      fixation:a case series.
AB  - Talus fractures are relatively rare injuries, accounting for approximately 3% of
      all foot fractures. Fractures of the talar neck account for almost 50% of all
      talus fractures. Diagnosis and treatment of these fractures play an important
      role in patients' outcomes. Treatment of talar neck fractures has slowly evolved
      from closed treatment to open reduction and internal fixation. Treatment of type
      I and type II talar neck fractures is debated in the orthopedic community.
      Choosing which treatment to perform depends on injury severity, associated
      injuries, and surgeon experience and preference. In this article, we report on
      our retrospective review of all talar neck fractures treated with closed
      reduction and percutaneous fixation between 1996 and 2001 at the Pennsylvania
      State University Milton S. Hershey Medical Center.

PMID- 21720594
TI  - Periarticular locking plate vs intramedullary nail for tibiotalocalcaneal
      arthrodesis: a biomechanical investigation.
AB  - Augmented retrograde intramedullary (IM) nail fixation was compared with
      augmented periarticular locking- plate fixation for tibiotalocalcaneal
      arthrodesis. Specimens in 10 matched pairs were randomly assigned to a fixation
      construct and loaded cyclically in dorsiflexion. The groups did not differ in
      initial or final stiffness, load to failure, or construct deformation. No
      correlation was found between bone mineral density and construct deformation for
      either group. A humeral locking plate may be a viable alternative to an IM nail
      for tibiotalocalcaneal fixation in cases not amenable to IM nailing.

PMID- 21720595
TI  - Electromyography nerve conduction velocity evaluation of children with clubfeet.
AB  - Neurologic deficit has been implicated as a possible etiology for clubfoot and a
      cause for recurrent deformity in patients who have undergone clubfoot surgery. In
      the study reported here, we wanted to determine if clubfoot patients with
      peroneal weakness had any neurologic deficits on electromyography nerve
      conduction velocity (EMG-NCV) studies before surgery and if there was any
      association between neurologic deficit and clubfoot recurrence. We reviewed the
      EMG-NCV studies of 36 patients involving 57 cases of idiopathic clubfoot and
      recurrence of the deformity or muscle weakness. In the clubfoot patients with
      weak peroneal muscle and no prior surgical history, 45% of the studies were
      interpreted as normal, 20% as neuropathic, 15% as mixed myopathic and
      neuropathic, 10% as radicular, and 10% as myopathic. In the clubfoot patients
      with recurrence after clubfoot repair surgeries, 57% had abnormal EMG-NCV
      studies. Specifically, peroneal mononeuropathy was the most common disorder (41%
      of clubfoot patients treated surgically). Awareness of a significant incidence of
      neurologic deficit may help in preoperative planning by indicating that
      ultimately a tendon transfer may be necessary to obtain a plantigrade foot.

PMID- 21720596
TI  - Challenges and solutions for total hip arthroplasty in treatment of patients with
      symptomatic sequelae of developmental dysplasia of the hip.
AB  - Conditions that adversely affect a child's hip alignment, joint congruity, or
      articular surfaces often result in joint destruction associated with pain and
      motion limitation later in life. The usual culprits are developmental dysplasia
      of the hip (DDH), slipped capital femoral epiphysis, Legg-Calve-Perthes disease,
      juvenile rheumatoid arthritis, infection, trauma, and neoplasm. In this review,
      we address DDH, the most common cause of secondary osteoarthritis of the hip.
      Symptomatic sequelae of DDH present challenges for total hip arthroplasty,
      including excessive proximal femoral anteversion, narrowing of the medullary
      canal, acetabular anteversion, verticality, hypoplasia and incongruity,
      pseudoacetabulum, and neurovascular shortening. Presiding corrective femoral
      and/or acetabular osteotomies, as well as retained hardware, further complicate
      total hip arthroplasty. This review emphasizes evaluation of hip morphology while
      considering reconstructive techniques and implants.

PMID- 21720597
TI  - Partial tears of the anterior cruciate ligament: diagnosis and treatment.
AB  - In sports medicine, diagnosis and treatment of partial tears of the anterior
      cruciate ligament (ACL) continue to be difficult. Partial tears of the ACL are
      common, representing 10% to 28% of all ACL tears. As our understanding of the
      anatomy of the native ACL improves, our accuracy in diagnosing these injuries
      increases. The advent of magnetic resonance imaging (MRI) and recognition of
      injury patterns have more clearly delineated the pathoanatomy in a majority of
      these cases. Natural history studies following patients with these injuries have
      demonstrated that fewer than 50% of patients return to their preinjury activity
      level. Several studies have also documented that progression to complete rupture
      is a common outcome for patients who want to return to an active lifestyle.
      Treatment options include conservative modalities (eg, activity modification,
      functional rehabilitation, functional bracing) and surgery (eg, thermal shrinkage
      of remaining ACL, complete reconstruction, newer techniques to augment or
      reconstruct the damaged portion of the native ligament). Studies comparing
      conservative treatments with more aggressive operative interventions are required
      to fully evaluate the efficacy of these treatments.

PMID- 21720598
TI  - Delayed fracture of a zirconium head after total hip arthroplasty.
AB  - We present a case of fracture of a zirconium head after a cemented total hip
      arthroplasty. The fracture occurred 81 months after the index operation without
      any history of trauma. The patient was thin, not participating in sports, and the
      zirconium head had 0-mm neck length. Preoperative radiographs demonstrated
      aseptic loosening of both components and significant polyethylene wear. Fracture
      pattern was unusual as the major fragment was half of the head. A revision was
      performed to a cementless arthroplasty. The authors have obtained the patient's
      informed written consent for print and electronic publication of the case report.

PMID- 21720599
TI  - Total hip arthroplasty in above-knee amputees: a case report.
AB  - There are previous case reports in the literature that describe total knee and
      total hip arthroplasty (THA) in below-knee amputees, but we could find no case
      reports on above-knee amputees (AKAs) who have severe osteoarthritis of the hip.
      We present a case involving an AKA who developed severe osteoarthritis of the
      ipsilateral hip. Out patient underwent THA with a satisfactory postoperative
      outcome. Technical considerations for AKAs undergoing THA are also reviewed.

PMID- 21720600
TI  - Remodeling and repair of orthopedic tissue: role of mechanical loading and
      biologics: part II: cartilage and bone.
AB  - Orthopedic tissues respond to mechanical loads to maintain normal homeostasis and
      in response to injury. As the body of work on this continues to grow, it is
      important to synthesize the recent studies across tissues and specialties with
      one another and with past studies. Hence, this review highlights the knowledge
      gained since 2000, with only few exceptions, concerning the effects of mechanical
      load and biologics on remodeling and repair of orthopedic tissue.

PMID- 21720601
TI  - Modes of failure of knotted and knotless suture anchors in an arthroscopic
      bankart repair model with the capsulolabral tissues intact.
AB  - The purpose of this study was to assess failure modes of knotless and knotted
      anchors in a Bankart repair model with the capsulolabral soft tissues intact.
      Previous reports used a model stripped of soft tissues. In 8 matched pairs of
      cadaver shoulders, a Bankart lesion was repaired arthroscopically using either 2
      Bio-SutureTak anchors (Arthrex, Naples, Florida) or 2 Bioknotless anchors (Mitek,
      Westwood, Massachusetts). The shoulders were mounted with the repaired
      capsulolabral tissues attached to a custom sinusoidal clamp, and were tested in
      cyclic loading (20-80 N, 100 cycles, 0.5 mm/s) and then load to failure (1.25
      mm/s). Cut-through at the suture-tissue interface (23/32 anchors) was more common
      than pullout at the anchor-bone interface (9/32) as a mode of failure (P = .02).
      Failure at the suture-tissue interface occurred in 10/16 knotted and 13/16
      knotless anchors. Mean (SD) ultimate load of knotted vs knotless anchors was
      125.3 (67.4) N and 96.9 (95.1) N, respectively. Mean (SD) stiffness of knotted vs
      knotless anchors was 20.9 (6.4) N/mm and 19.8 (8.6)N/mm, respectively. We
      concluded that both knotted and knotless anchors fail most often at the suture
      tissue interface. The tested model with the capsulolabral tissues intact is
      distinct from previous models, which tested the anchor-bone interface only.

PMID- 21720602
TI  - Proximal humerus osteolysis after revision rotator cuff repair with bioabsorbable
      suture anchors.
AB  - Biodegradable anchors were designed to provide secure fixation while allowing for
      later resorption and replacement by host tissue. First-generation implants
      degraded relatively rapidly and caused foreign-body reactions, synovitis,
      fragmentation, and osteolysis. Newer implants have similar complications. It is
      not known if the primary cause of the osteolysis is biological (precipitated by
      breakdown products of the polymer) or mechanical (caused by initial loss of
      implant stability). Case reports have described glenoid osteolysis around
      biodegradable suture anchor placement for shoulder stabilization, but up until
      now, to our knowledge, only 1 case of proximal humerus osteolysis has been
      reported for these implants. Here we describe a semicrystalline, poly-L-lactic
      acid bioabsorbable suture anchor failure after revision rotator cuff repair with
      subsequent humeral tuberosity osteolysis.

PMID- 21720603
TI  - The effect of butyric acid on normal tendons: a potential stimulus for
      extracellular matrix expression.
AB  - We propose comparing angiogenic effects of butyric acid (BA)-impregnated suture
      vs control suture on an aged tendon model. Twenty-four 3-year-old rabbits
      underwent bilateral Achilles tendon exposure. BA-impregnated orthopedic suture
      was sutured into one side, and a control orthopedic suture into the contralateral
      side similarly. The rabbits were sacrificed at 7, 30, and 45 days and the tendons
      harvested for gross, histologic, and biochemical study. Histologically, there was
      increased vascularity/cell migration at all time points in the BA-treated
      tendons; proteoglycan expression (ie, safranin O staining) increased at 30 and 45
      days. DNA concentration was significantly (P = .05) higher in the BA-treated
      tendon group relative to the control group at 7 days but was unchanged at 30 and
      45 days. Similarly, messenger RNA (mRNA) expression of vascular endothelial
      growth factor (VEGF) was significantly (P = .05) higher in the BA-treated tendon
      at 7 days. A trend (P = .12) for higher expression in the BA group also was found
      at 30 days.

PMID- 21720604
TI  - Do seat belts and air bags reduce mortality and injury severity after car
      accidents?
AB  - We studied National Trauma Data Bank data to determine the effectiveness of car
      safety devices in reducing mortality and injury severity in 184,992 patients
      between 1988 and 2004. Safety device variables were seat belt used plus air bag
      deployed; only seat belt used; only air bag deployed; and, as explicitly coded,
      no device used. Overall mortality was 4.17%. Compared with the no-device group,
      the seat-belt-plus-air-bag group had a 67% reduction in mortality (adjusted odds
      ratio [AOR], 0.33; 99% confidence interval [CI], 0.28-0.39), the seatbelt- only
      group had a 51% mortality reduction (AOR, 0.49; 99% CI, 0.45-0.52), and the air
      bag-only group had a 32% mortality reduction (AOR, 0.68, 99% CI, 0.57-0.80).
      Injury Severity Scores showed a similar pattern.

PMID- 21720605
TI  - Clinical and radiographic evaluation of sagittal imbalance: a new radiographic
      assessment.
AB  - In this article, we describe a case series study involving a new radiologic
      evaluation of sagittal imbalance. We review the current radiologic assessment of
      sagittal imbalance and introduce a new radiologic evaluation that helps in ruling
      out hip flexion contracture as the primary cause of sagittal imbalance and the
      type and level of spinal osteotomy required to regain sagittal balance. Sagittal
      imbalance is important in spinal deformity assessment. Studies have confirmed
      that overall clinical outcomes and patient satisfaction with surgery were best in
      cases that resulted in an increase in lumbar lordosis. For this study, radiologic
      assessment of sagittal imbalance was conducted on a long, 14 * 51-inch upright
      lateral plain radiograph that included the proximal femur and the entire spine.
      The radiograph was taken with the arms at 45 degrees  forward flexion and the
      hips and knees fully extended. The femoral axis line was drawn and extended
      cephalad. The C7 offset, the perpendicular distance between the femoral axis line
      and the center of C7, represented the degree of sagittal imbalance. The angle
      between the femoral axis line and a line extending from the center of C7 to the
      vertebra at the level of the proposed osteotomy--the Seattle angle--predicted how
      much correction was required to bring the C7 plumb in line with the femoral axis
      and to decrease the C7 offset, thus regaining sagittal balance. The proposed
      method was used to evaluate 10 consecutive patients who required spinal
      osteotomies to regain sagittal balance. Preoperative and postoperative plain
      radiographs were assessed twice, at a 6-week interval, by an independent spine
      surgeon and a musculoskeletal radiologist. Cohen kappa correlation coefficients
      were used to calculate intraobserver and interobserver reliability. The 2
      reviewers' intraobserver reliability was excellent (kappas = 0.98, 0.93).
      Interobserver reliability was lower but good (kappa = 0.76). Inclusion of the
      proximal femur on the long upright lateral plain radiograph of the entire spine
      and identification of the relation between the femoral axis line and the center
      of C7 are important in evaluating sagittal imbalance. Excellent intraobserver
      reliability, coupled with good interobserver reliability, suggest that this new
      radiologic assessment method can be helpful in preoperative assessment of
      sagittal imbalance.

PMID- 21720606
TI  - Expandable titanium cages for thoracolumbar vertebral body replacement: initial
      clinical experience and review of the literature.
AB  - Reconstruction of the anterior and middle column after vertebrectomy is essential
      for restoring stability. Use of expandable implants is supported by an emerging
      body of literature. Newer expandable cages have some advantages over traditional
      mesh implants, structural allograft, and polyetheretherketone or carbon fiber
      cages. To determine the utility of an expandable titanium cage in spine
      reconstruction, we conducted a retrospective cohort study of patients who had
      undergone this reconstruction after single or multilevel thoracic and/or lumbar
      vertebrectomy. Here we report on our experience using expandable cages at 2 large
      academic medical centers. Outcome was based on both clinical and radiographic
      measures with cross-sectional analysis. Thirty-five patients were identified. Of
      these, 20 had undergone surgery for neoplasm, 8 for trauma, and 7 for infection.
      Mean follow-up was 31 months (range, 12 to 50 months). Early postoperative
      kyphosis correction, restoration of sagittal alignment at 12 months, and
      reduction in visual analog scale pain score were significant. There was no
      difference in Oswestry Disability Index or height restoration. Expandable
      intervertebral body strut grafts appear to be a safe and effective option in
      spine reconstruction after a vertebrectomy and should be considered a treatment
      option.

PMID- 21720607
TI  - Minimally invasive plate osteosynthesis for proximal humerus fractures:
      functional results of treatment.
AB  - Proximal humeral fractures can safely and effectively be treated with minimally
      invasive plate osteosynthesis (MIPO). Twenty-one patients treated with MIPO for 2
      , 3-, and 4-part proximal humerus fractures were treated at a mean 6.8 days
      (range, 1-24 days) after injury and followed for a mean of 24 months (range, 5-38
      months). All fractures healed by 8 weeks postoperatively, with reductions "good"
      in 18 (86%) of patients and "fair" in 3 (14%). There were no infections or nerve
      or vascular injuries. One patient had loss of reduction that healed but required
      hardware removal. The neck-shaft angle was measured intraoperatively and at final
      follow-up, with mean (SD) of 139 degrees  (9.3; range, 123 degrees - 156 degrees
      ) and 138 degrees  (8.9; range, 123 degrees - 159 degrees ), respectively. Mean
      (SD) displacement from the most superior aspect of the humeral head articular
      surface to the top of the greater tuberosity was 4.3 (10) mm. Mean (SD) active
      range of motion was 143 degrees  (35.04; range, 80 degrees - 180 degrees ) for
      forward flexion, 118 degrees  (46.8; range, 45 degrees - 180 degrees ) for
      elevation, and 33 degrees  (19.2; range, 10 degrees - 65 degrees ) for external
      rotation. The mean Disability of the Arm, Shoulder, and Hand (DASH) score was
      25.95 (range, 0-80). Excluding patients with associated injuries, a statistically
      significant difference (P<.05) was found in the DASH scores for those patients
      with greater tuberosity displacements between 3 mm and 8 mm and those patients
      with greater tuberosity displacement greater than 8 mm inferior to the articular
      surface. Clinical outcomes depended upon reduction of the greater tuberosity,
      which is facilitated by the MIPO technique.

PMID- 21720608
TI  - Alendronate therapy in polyostotic fibrous dysplasia presenting with pathologic
      fracture.
AB  - Polyostotic fibrous dysplasia (PFD) is characterized by developmental failure in
      the remodeling of primitive bone to mature lamellar bone. PFD presents with bone
      pain, increased bone fragility, deformities, and fractures. Bisphosphonates are
      the only agents available for medical management.1,2 Intravenous (IV) pamidronate
      is the established treatment for symptomatic bone involvement in PFD.3,4 Oral
      alendronate holds promise because of its comparable outcomes, lower cost, and
      ease of administration.5 The patient described in this case report provided
      written informed consent for its print and electronic publication after reviewing
      the complete manuscript and skeletal radiographic images.

PMID- 21720609
TI  - Open fracture as a rare complication of olecranon enthesophyte in a patient with
      gout.
AB  - Enthesophytes are analogous to osteophytes of osteoarthritis. Enthesopathy is the
      pathologic change of the enthesis, the insertion site of tendons, ligaments, and
      joint capsules on the bone. In gout, the crystals of monosodium urate monohydrate
      may provoke an inflammatory reaction that eventually may lead to ossification at
      those sites (enthesophytes). Here we report the case of a man with chronic gout
      who sustained an open fracture of an olecranon enthesophyte when he fell on his
      left elbow. To our knowledge, no other case of open fracture of an enthesophyte
      has been reported in the English literature.

PMID- 21720610
TI  - Structure and order of DODAB bilayers modulated by dicationic gemini surfactants.
AB  - Cationic liposomes have been extensively studied from the experimental and
      theoretical standpoints, motivated both by their fundamental interest and by
      potential applications in drug delivery and gene therapy. However, a detailed
      understanding of the nature of interactions within mixed bilayers containing
      cationic gemini surfactants is still lacking. This work focuses on the structural
      and dynamic properties of DODAB membranes in the presence of dicationic gemini
      surfactants. A thermodynamic characterization of the phase transitions in the
      mixed systems has been carried out by differential scanning calorimetry, while
      insight into the molecular interactions in the bilayer has been provided by
      molecular dynamics. For this purpose, variations in the gemini spacer and tail
      length, as well as in the respective molar fraction, have been included in both
      experimental and simulation studies. The results indicate that the influence of
      cationic gemini surfactants upon the thermotropic behavior and degree of order of
      DODAB structures is controlled by a complex interplay between charge density,
      conformation and hydrophobic effects, for which a detailed rationale is provided.

PMID- 21720611
TI  - Vibrational dynamics of deoxyguanosine 5'-monophosphate following UV excitation.
AB  - The relaxation dynamics of the DNA nucleotide deoxyguanosine 5'-monophosphate
      (dGMP) following 266 nm photoexcitation has been studied by transient IR
      spectroscopy with femtosecond time resolution. The induced dynamics of the amide
      I (carbonyl) stretch, the asymmetric guanine ring stretch and the phosphate
      asymmetric stretch are monitored in the region 1000-1800 cm(-1). Excitation and
      subsequent rapid internal conversion to a "hot" ground state is reflected by
      depletion of the vibrational ground states of the amide I stretch and guanine
      ring stretch. However, the vibrational ground state of the phosphate is left
      unperturbed, indicating the absence of vibrational coupling between the guanine
      ring system and the phosphate group. The vibrational ground state of the amide I
      is repopulated in 2.5 ps (+/-0.2 ps) while it takes 3.7 ps (+/-0.5 ps) to
      repopulate the guanine ring vibration. This article discusses two possible
      relaxation pathways of dGMP, as well as the implications of the weak phosphate
      dynamics.

PMID- 21720612
TI  - Diarylethene-dihydroazulene multimode photochrome: a theoretical spectroscopic
      investigation.
AB  - Using Time-Dependent Density Functional Theory, we have assessed the structural,
      energetic and spectroscopic properties of a hybrid diarylethene-dihydroazulene
      multi-addressable switch synthesized by Mrozek et al. [Chem. Commun., 1999, 1487
      1488]. All possible closed/open structures have been considered and the different
      activation barriers along each reaction path have been evaluated. The
      determination of the energetic profiles allowed us to pinpoint the thermally
      possible reactions. To simulate the electronic absorption spectra of this compact
      two-way four-state hybrid compound, we relied on a PCM-TD-DFT approach combined
      with a molecular orbital analysis. Key insights are reached and the experimental
      photochromic properties of this multi-component switch are rationalised. From a
      more methodological point of view, this work also shows that range-separated
      hybrid functionals (CAM-B3LYP and omegaB97XD) allow to reproduce the measured
      spectroscopic features with a remarkable accuracy.

PMID- 21720613
TI  - Small molecules in biology.

PMID- 21720614
TI  - Climate change drives warming in the Hudson River Estuary, New York (USA).
AB  - Estuaries may be subject to warming due to global climate change but few studies
      have considered the drivers or seasonality of warming empirically. We analyzed
      temperature trends and rates of temperature change over time for the Hudson River
      estuary using long-term data, mainly from daily measures taken at the
      Poughkeepsie Water Treatment Facility. This temperature record is among the
      longest in the world for a river or estuary. The Hudson River has warmed 0.945 
      degrees C since 1946. Many of the warmest years in the record occurred in the
      last 16 years. A seasonal analysis of trends indicated significant warming for
      the months of April through August. The warming of the Hudson is primarily
      related to increasing air temperature. Increasing freshwater discharge into the
      estuary has not mitigated the warming trend.

PMID- 21720615
TI  - Zeolites X and A crystallization compared by simultaneous UV/VIS-Raman and X-ray
      diffraction.
AB  - The hydrothermal crystallizations of two zeolite topologies (FAU and LTA) have
      been studied by simultaneous UV-Raman spectroscopy and X-ray diffraction in a
      home built setup. A wide angle X-ray diffractometer has been redesigned and
      combined with Raman components. The results revealed, despite similar structures
      of the starting gels, different aluminosilicate species evolved in the two
      systems, prior to emerging Bragg scattering. Based on this the sodalite cage
      could be ruled out as a common building unit for both frameworks.

PMID- 21720616
TI  - Ab initio intermolecular potential energy surface and thermophysical properties
      of hydrogen sulfide.
AB  - A six-dimensional potential energy hypersurface (PES) for two interacting rigid
      hydrogen sulfide molecules was determined from high-level quantum-mechanical ab
      initio computations. A total of 4016 points for 405 different angular
      orientations of two molecules were calculated utilizing the counterpoise
      corrected supermolecular approach at the CCSD(T) level of theory and
      extrapolating the calculated interaction energies to the complete basis set
      limit. An analytical site-site potential function with eleven sites per hydrogen
      sulfide molecule was fitted to the interaction energies. The PES has been
      validated by computing the second pressure virial coefficient, shear viscosity,
      thermal conductivity and comparing with the available experimental data. The
      calculated values of volume viscosity were not used to validate the potential as
      the low accuracy of the available data precluded such an approach. The second
      pressure virial coefficient was evaluated by means of the Takahashi and Imada
      approach, while the transport properties, in the dilute limit, were evaluated by
      utilizing the classical trajectory method. In general, the agreement with the
      primary experimental data is within the experimental error for temperatures
      higher than 300 K. For lower temperatures the lack of reliable data indicates
      that the values of the second pressure virial coefficient and of the transport
      properties calculated in this work are currently the most accurate estimates for
      the thermophysical properties of hydrogen sulfide.

PMID- 21720617
TI  - Structural characterization of TaMe3Cl2 and Ta(PMe3)2Me3Cl2, a pair of five and
      seven-coordinate d0 tantalum methyl compounds.
AB  - The trimethylphosphine complex Ta(PMe(3))(2)Me(3)Cl(2) has been synthesized by
      addition of PMe(3) to TaMe(3)Cl(2). The molecular structures of both TaMe(3)Cl(2)
      and Ta(PMe(3))(2)Me(3)Cl(2) have been determined by X-ray diffraction thereby
      demonstrating that, in the solid state, these complexes respectively adopt
      trigonal bipyramidal and capped trigonal prismatic geometries.

PMID- 21720618
TI  - High resolution mapping of surface reduction in ceria nanoparticles.
AB  - Surface reduction of ceria nano octahedra with predominant {111} and {100} type
      surfaces is studied using a combination of aberration-corrected Transmission
      Electron Microscopy (TEM) and spatially resolved electron energy-loss
      spectroscopy (EELS) at high energy resolution and atomic spatial resolution. The
      valency of cerium ions at the surface of the nanoparticles is mapped using the
      fine structure of the Ce M(4,5) edge as a fingerprint. The valency of the surface
      cerium ions is found to change from 4+ to 3+ owing to oxygen deficiency
      (vacancies) close to the surface. The thickness of this Ce(3+) shell is measured
      using atomic-resolution Scanning Transmission Electron Microscopy (STEM)-EELS
      mapping over a {111} surface (the predominant facet for this ceria morphology),
      {111} type surface island steps and {100} terminating planes. For the {111}
      facets and for {111} surface islands, the reduction shell is found to extend over
      a single fully reduced surface plane and 1-2 underlying mixed valency planes. For
      the {100} facets the reduction shell extends over a larger area of 5-6 oxygen
      vacancy-rich planes. This finding provides a plausible explanation for the higher
      catalytic activity of the {100} surface facets in ceria.

PMID- 21720619
TI  - Fullerenes encaging metal clusters--clusterfullerenes.
AB  - Clusterfullerenes represent a novel branch of endohedral fullerenes, which are
      characterized by a robust fullerene cage with metal clusters encaged in its
      hollow. Since the discovery of nitride clusterfullerenes (NCFs) in 1999, the
      family of clusterfullerenes has been significantly expanded within the past
      decade, with new members including carbide clusterfullerenes (CCFs), hydrocarbide
      clusterfullerenes (HCCFs), oxide clusterfullerenes (OCFs), sulfide
      clusterfullerenes (SCFs), and carbonitride clusterfullerenes (CNCFs). We first
      present the classification of clusterfullerenes and list all the
      clusterfullerenes reported to date. For each type of clusterfullerenes, we review
      in detail their synthesis, separation, intriguing molecular structures and
      properties. For NCFs, as the first and most important clusterfullerenes, we point
      out the significance of their discovery and focus on their new synthesis and
      separation methods as well as the new advances. Finally the potential
      applications of clusterfullerenes are addressed. We conclude that
      clusterfullerenes appear to be the fastest growing family of endohedral
      fullerenes up to now, and emphasize the importance of exploring new structures
      and chemical functionalizations of clusterfullerenes.

PMID- 21720620
TI  - Annealing effects on the photovoltaic performance of all-conjugated poly(3
      alkylthiophene) diblock copolymer-based bulk heterojunction solar cells.
AB  - The effects of thermal and solvent vapor annealing on the photovoltaic
      performance of a new class of all-conjugated poly(3-butylthiophene)-b-poly(3
      hexylthiophene) diblock copolymer/PC(71)BM bulk heterojunction (BHJ) solar cells
      were scrutinized and theoretically analyzed using the single diode model combined
      with experimental measurements. The meanings of physical parameters in the model
      were elucidated in the context of crystalline order and phase separation to gain
      fundamental insight into the mechanism of annealing effects on the device
      performance of a new class of all-conjugated diblock copolymer-based BHJ solar
      cells.

PMID- 21720621
TI  - A 3D Co(II) framework with alternating vertex- and edge-sharing Delta-ribbons
      showing a two-step field-induced magnetic transition.
AB  - A novel 3D framework with vertex- and edge-sharing Delta-ribbons extended by ip(2
      ) connectors, {[Co(7)(H(2)O)(2)(MU(3)-OH)(4)(atz)(2)(ip)(4)].5H(2)O}(n) (atz(-) =
      5-amino-tetrazolate and ip(2-) = isophthalate), exhibits a two-step field-induced
      metamagnetic transition from an antiferromagnetic ordering to a weak spontaneous
      magnetization state by spin-competition at 2.0 KOe, followed by a spin-flop
      transition at 22.5 KOe.

PMID- 21720622
TI  - Photoredox catalyzed C-P bond forming reactions-visible light mediated oxidative
      phosphonylations of amines.
AB  - A visible light mediated, carbon-phosphorus bond forming reaction has been
      developed. With the use of a readily available photoredox catalyst, alpha-amino
      phosphonates were obtained in good yields under mild reaction conditions.

PMID- 21720623
TI  - o-Carborane as an electron-transfer mediator in electrocatalytic reduction.
AB  - Electron transfer behavior of 1,2-diphenyl-o-carborane was investigated by cyclic
      voltammetry (CV). In the presence of 1,2-dibromo-1,2-diphenylethane, a
      significant catalytic current was observed. The macroscale electrocatalytic
      reduction of the dibromide using a catalytic amount (1 mol%) of the carborane
      mediator afforded the desired trans-stilbene in excellent yield.

PMID- 21720628
TI  - Control of molecular architecture by steric factors: mononuclear vs polynuclear
      manganese(III) compounds with tetradentate N2O2 donor Schiff bases.
AB  - Three manganese(III) compounds, [Mn(III)(vanoph)(DMF)(H(2)O)]ClO(4) (1),
      [Mn(III)(vanoph)(N(3))(H(2)O)].2H(2)O (2) and [Mn(III)(saloph)(MU(1,3)-N(3))](n)
      (3), where H(2)vanoph = N,N'-(1,2-phenylene)-bis(3-methoxysalicylideneimine),
      H(2)saloph = N,N'-(1,2-phenylene)-bis(salicylideneamine) are tetradentate
      N(2)O(2) ligands and DMF = N,N-dimethylformamide, have been prepared and
      characterised by elemental analysis, IR and UV-Vis spectroscopy and single
      crystal X-ray diffraction studies. Compounds 1 and 2 are monomeric but compound 3
      consists of a chain system with the repeating unit [Mn(III)(saloph)(N(3))]
      bridged by MU-1,3 azide. Compound 1 crystallises in monoclinic space group
      P2(1)/n with cell dimensions of a = 11.1430(2), b = 16.3594(3), c = 15.4001(3) A,
      beta = 108.417(1), Z = 4 whereas compounds 2 and 3 crystallise in orthorhombic
      space groups Pbca and Pna2(1), respectively, with cell dimensions of a =
      16.069(3), b = 15.616(3), c = 18.099(4) A, Z = 8 (for 2) and a = 18.760(9), b =
      13.356(5), c = 6.616(3) A, Z = 4 (for 3). In all the compounds, Mn(III) has a six
      coordinated pseudo-octahedral geometry in which O(2), O(3), N(1) and N(2) atoms
      of the deprotonated di-Schiff base constitute the equatorial plane. In both
      compounds 1 and 2, water molecules are present in the fifth coordination sites in
      the apical positions. The sixth coordination sites are occupied by one O atom of
      a solvent DMF in compound 1 and an N atom of azide in compound 2. The coordinated
      water initiates hydrogen-bonded networks in both compounds 1 and 2 to form well
      isolated supramolecular dimers. At room temperature the chi(M)T values for the
      compounds 1 and 2 remain almost constant until 30 K. Below this temperature, the
      chi(M)T values drastically drop to 0.72 cm(3) mol(-1) K for 1 and 0.52 cm(3) mol(
      1) K for 2. The best fits were obtained with J = -0.92 cm(-1), |D| = 2.05 cm(-1),
      g = 2.0 and R = 8.1 * 10(-4) for 1 and J = -1.16 cm(-1), |D| = 2.05 cm(-1), g =
      2.0 and R = 1.2 * 10(-3) for 2. However, in compound 3, two axial positions are
      occupied by the azide ions. The Mn...Mn repeating distance is 6.616 A along the
      chain. Magnetic characterisation shows that the MU(1,3)-bridging azide ion mainly
      transmits an antiferromagnetic interaction (J = -6.36 cm(-1)) between Mn(III)
      ions. The presence of two methoxy groups increases the steric crowding in the
      H(2)vanoph moiety and thereby inhibits the formation of a polynuclear compound
      with this ligand.

PMID- 21720629
TI  - Morphological and mechanical properties of alkanethiol Self-Assembled Monolayers
      investigated via BiModal Atomic Force Microscopy.
AB  - Alkanethiol Self-Assembly Monolayers (SAMs) were investigated by means of BiModal
      Atomic Force Microscopy. Morphological and mechanical properties show a parabolic
      trend vs. the chain length n, which is ascribed to the disorder at the SAMs/Au
      interface. This explains the trend of charge injection across SAMs in organic
      field effect transistors.

PMID- 21720630
TI  - Palladium-catalyzed haloallylation of aromatic ynol ethers with allyl chlorides:
      a highly regio- and stereoselective approach to (1E)-alpha-chloroenol ethers.
AB  - Described herein is a Pd-catalyzed haloallylation of aromatic ynol ethers and
      allyl chlorides, allowing facile access to (1E)-alpha-chloroenol ethers in a
      highly regio- and stereoselective manner. The synthetic utility of this method is
      demonstrated well by the synthesis of the stereodefined multisubstituted enol
      ethers and alpha-allylated carbonyl compounds.

PMID- 21720631
TI  - Exploring the self-assembly of glycopeptides using a diphenylalanine scaffold.
AB  - Diphenylalanine, a key building block for organic nanotechnology, forms discrete,
      rigid and hollow nanotubes that are assembled spontaneously upon their dilution
      from organic phase into aqueous solution. Here we report the efficient
      preparation of several S-linked glycosylated diphenylalanine analogues bearing
      different monosaccharide, di-saccharide and sialic acid residues. The self
      assembly studies revealed that these glycopeptides adopted various structures and
      glycosylation could be a tool to manipulate the self-assembly process. Moreover,
      the solubility of these analogues was found to be much greater than
      diphenylalanine, which could open new applications based on these nanostructures.

PMID- 21720632
TI  - Biotin-, fluorescein- and 'clickable' conjugates of phospha-oseltamivir as probes
      for the influenza virus which utilize selective binding to the neuraminidase.
AB  - The synthesis of conjugates of phospha-oseltamivir to the well established
      reporter groups fluorescein and biotin and an approach to multimeric inhibitors
      is described. We report powerful inhibition of the influenza neuraminidase by
      these probes and quantify fluorescence quenching during binding of the
      fluorescein conjugate through titration with the neuraminidase. Thus, we show
      that they could be useful tools to efficiently inhibit, detect and quantify the
      virus and the neuraminidase in biological systems.

PMID- 21720633
TI  - Studies of the fluorescence light-up effect of amino-substituted
      benzo[b]quinolizinium derivatives in the presence of biomacromolecules.
AB  - A comparative study of the ability of amino-substituted benzo[b]quinolizinium
      derivatives to act as DNA- or protein-sensitive fluorescent probes is presented.
      Spectrophotometric titrations, DNA denaturation studies and viscometric
      titrations showed that all tested aminobenzo[b]quinolizinium derivatives
      intercalate into DNA with binding constants K(b) = 10(4)-10(5) M(-1). The intense
      fluorescence of the 9-aminobenzo[b]quinolizinium (Phi(fl) = 0.41) as well as the
      intrinsically very weak emission of the 7-aminobenzo[b]quinolizinium (Phi(fl) <
      0.005) are quenched by the addition of DNA, most likely caused by a photoinduced
      electron transfer (PET) between the excited intercalated ligand and the DNA
      bases. The 6-aminobenzo[b]quinolizinium (1b) and the 6-amino-9
      bromobenzo[b]quinolizinium (1c) exhibit very low fluorescence intensity in water
      (Phi(fl) < 0.005). However, in water-glycerol mixtures the emission intensity
      increases by factors of 56 (1b) and 27 (1c) with increasing glycerol content of
      the solution (0-100 wt%), which indicates the radiationless deactivation of the
      excited state of 1b and 1c due to a torsional relaxation, i.e. rotation about the
      exocyclic C(ar)-NH(2) bond. In the case of the bromo-substituted derivative 1c, a
      viscosity-independent heavy-atom-effect of the bromo substituent leads to
      additional quenching. The association of 1b and 1c with ds DNA leads to a
      restricted conformational flexibility of the intercalated ligand and results in
      an increase of fluorescence intensity. This effect is particularly strong in the
      presence of poly[dA-dT]-poly[dA-dT]. Upon association with ct DNA or poly[dG-dC]
      poly[dG-dC] only very small enhancement of emission intensity (1b) or even a
      slight quenching (1c) of the fluorescence was observed because of the interfering
      PET reaction with the guanine residues. Preliminary experiments reveal that the 6
      aminobenzo[b]quinolizinium derivatives 1b and 1c may also be employed as protein
      sensitive probes, because their emission intensity increases upon association
      with selected albumins.

PMID- 21720634
TI  - Concurrent display of both alpha- and beta-turns in a model peptide.
AB  - This article describes a model peptide that concurrently displays both alpha- and
      beta-turns, as demonstrated by structural investigations using single crystal X
      ray crystallography and solution-state NMR studies. The motif reported herein has
      the potential for the design of novel conformationally ordered synthetic
      oligomers with structural architectures distinct from those classically observed.

PMID- 21720635
TI  - Toward understanding macrocycle specificity of iron on the dioxygen-binding
      ability: a theoretical study.
AB  - In an effort to examine the interaction between dioxygen and iron-macrocyclic
      complexes, and to understand how this interaction was affected by those different
      macrocyclic ligands, dioxygen binding with iron-porphyrin, iron-phthalocyanine,
      iron-dibenzotetraaza[14]annulene, and iron-salen complexes is investigated by
      means of quantum chemical calculations utilizing Density Functional Theory (DFT).
      Based on the analysis of factors influencing the corresponding dioxygen binding
      process, it showed that different macrocyclic ligands possess different O-O bond
      distances, and different electronic configurations for the bound O(2) and non
      aromatic macrocyclic ligands favor dioxygen activation. Furthermore, the smaller
      the energy gap between the HOMO of iron-macrocyclic complexes and the LUMO of
      dioxygen, the more active the bound O(2) becomes, with a longer O-O bond distance
      and a shorter Fe-O bond length.

PMID- 21720636
TI  - Metabolic pathway visualization in living yeast by DNP-NMR.
AB  - Central carbon metabolism of living Saccharomyces cerevisiae is visualized by DNP
      NMR. Experiments are conducted as real time assays that detect metabolic
      bottlenecks, pathway use, reversibility of reactions and reaction mechanisms in
      vivo with subsecond time resolution.

PMID- 21720637
TI  - Stereocontrolled synthesis of oligonucleotide analogs containing chiral
      internucleotidic phosphorus atoms.
AB  - Oligonucleotides, in which one of the two nonbridging oxygen atoms of
      internucleotidic phosphates is replaced by a different type of atom or a
      substituent, are useful as therapeutic agents and probes to elucidate mechanisms
      of enzymatic reactions. The internucleotidic phosphorus atoms of these
      oligonucleotides are chiral, and the properties of these oligonucleotides are
      affected by the absolute configuration of the chiral phosphorus atoms. In order
      to address the issue of chirality, various methods have been developed to
      synthesize these P-chiral oligonucleotide analogs in a stereocontrolled manner.
      This critical review focuses on the recent progress in this field (123
      references).

PMID- 21720638
TI  - Methods for investigating G-quadruplex DNA/ligand interactions.
AB  - DNA is considered an important target for drug design and development. Until
      recently, the focus was on double-stranded (duplex) DNA structures. However, it
      has now been shown that single stranded DNA can fold into hairpin, triplex, i
      motif and G-quadruplex structures. The more interesting G-quadruplex DNA
      structures comprise four strands of stacked guanine (G)-tetrads formed by the
      coplanar arrangement of four guanines, held together by Hoogsteen bonds. The DNA
      sequences with potential to form G-quadruplex structures are found at the
      chromosomal extremities (i.e. the telomeres) and also at the intra-chromosomal
      region (i.e. oncogenic promoters) in several important oncogenes. The formation
      of G-quadruplex structures is considered to have important consequences at the
      cellular level and such structures have been evoked in the control of expression
      of certain genes involved in carcinogenesis (c-myc, c-kit, K-ras etc.) as well as
      in the perturbation of telomeric organization. It has been shown that the
      formation of quadruplexes inhibits the telomere extension by the telomerase
      enzyme, which is up-regulated in cancer cells. Therefore, G-quadruplex structures
      are an important target for drug design and development and there is a huge
      interest in design and development of small molecules (ligands) to target these
      structures. A large number of so-called G-quadruplex ligands, displaying varying
      degrees of affinity and more importantly selectivity (i.e. the ability to
      interact only with quadruplex-DNA and not duplex-DNA), have been reported. Access
      to efficient and robust in vitro assays is needed to effectively monitor and
      quantify the G-quadruplex DNA/ligand interactions. This tutorial review provides
      an overview of G-quadruplex ligands and biophysical techniques available to
      monitor such interactions.

PMID- 21720639
TI  - Structural evolution and magnetic properties of Co(II) coordination polymers
      varied from 1D to 3D constructed by 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene.
AB  - Seven Co(II) coordination polymers,
      [Co(btx)(3)(H(2)O)(2)](ClO(4))(2).(btx).2H(2)O (1),
      [Co(btx)(3)(H(2)O)(2)](BF(4))(2).(btx).2H(2)O (2),
      [Co(btx)(2)(H(2)O)(2)](NO(3))(2).2H(2)O (3), [Co(btx)(2)Cl(2)] (4),
      [Co(btx)(BA)(2)(H(2)O)(2)].2HBA (5), [Co(btx)(IPA)] (6) and
      [Co(3)(btx)(3)(BTA)(2)(H(2)O)(2)] (7) (btx = (1,4-bis(1,2,4-triazol-1
      ylmethyl)benzene), HBA = benzoic acid, H(2)IPA = isophthalic acid, H(3)BTA =
      benzene-1,3,5-tricarboxylic acid), have been hydrothermally synthesized and
      characterized. 1 and 2 are isostructural and show a 1D Co-MU(2)-btx-Co chain
      structure, in which btx acts as both a bridging and terminal ligand. 3 is also a
      1D chain structure but different from 1 and 2. The Co(II) ions are bridged by
      double MU(2)-btx to form Co(2)-btx(2) rings, which were further connected into 1D
      chains by sharing the Co(II) ions of the rings. 4 exists as a 2D grid with (4,4)
      topology structure. When aromatic acid was introduced to the synthetic system,
      three other coordination polymers 5-7 were obtained. In 5, the 1D chain is as
      that of 1, except that the terminal ligand was replaced by BA(-). 6 shows a two
      fold parallel interpenetration framework featuring a 6-c uninodal net with
      (3(3),4(6),5(5),6) Schlafli topological symbol. 7 is an interesting 3D framework,
      which contains a 2-nodal net motif with the unprecedented
      (3(6),4(2),5(6),6)(3(9),4(9),5(3))(2) topology structure. The influence of the
      varieties of the structures and magnetic properties are studied and discussed in
      detail.

PMID- 21720640
TI  - Maghemite (hematite) core (shell) nanorods via thermolysis of a molecular solid
      of Fe-complex.
AB  - An Fe-metal complex with 2'-hydroxy chalcone (2'-HC) ligands [Fe(III) (2'-hydroxy
      chalcone)(3)] is synthesized by a chemical route and is subjected to different
      thermal treatments. Upon thermolysis in air at 450  degrees C for 3 h the complex
      yields maghemite (gamma-Fe(2)O(3)) nanorods with a thin hematite (alpha
      Fe(2)O(3)) shell. X-Ray diffraction (XRD), Mossbauer spectroscopy, diffuse
      reflectance spectroscopy (UV-DRS), high resolution transmission electron
      microscopy (HR-TEM), field emission scanning electron microscopy (FE-SEM) and
      vibrating sample magnetometry (VSM) are used to characterize the samples. The
      stability of the ligand and the Fe-complex is further examined by using
      thermogravimmetric/differential thermal analysis (TGA/DTA). We suggest a residual
      ligand controlled mechanism for the formation of an anisotropic nanostructure in
      a crumbling molecular solid undergoing ligand decomposition. Since the band gap
      of iron oxide is in the visible range, we explored the use of our core shell nano
      rod sample for photocatalytic activity for H(2) generation by H(2)S splitting
      under solar light. We observed high photocatalytic activity for hydrogen
      generation (75 ml h(-1)).

PMID- 21720641
TI  - Pyrazolyl methyls prescribe the electronic properties of iron(II)
      tetra(pyrazolyl)lutidine chloride complexes.
AB  - A series of iron(II) chloride complexes of pentadentate ligands related to
      alpha,alpha,alpha',alpha'-tetra(pyrazolyl)-2,6-lutidine, pz(4)lut, has been
      prepared to evaluate whether pyrazolyl substitution has any systematic impact on
      the electronic properties of the complexes. For this purpose, the new
      tetrakis(3,4,5-trimethylpyrazolyl)lutidine ligand, pz**(4)lut, was prepared via a
      CoCl(2)-catalyzed rearrangement reaction. The equimolar combination of ligand and
      FeCl(2) in methanol gives the appropriate 1:1 complexes [FeCl(pz(R)(4)lut)]Cl
      that are each isolated in the solid state as a hygroscopic solvate. In solution,
      the iron(II) complexes have been fully characterized by several spectroscopic
      methods and cyclic voltammetry. In the solid state, the complexes have been
      characterized by X-ray diffraction, and, in some cases, by Mossbauer
      spectroscopy. The Mossbauer studies show that the complexes remain high spin to 4
      K and exclude spin-state changes as the cause of the surprising solid-state
      thermochromic properties of the complexes. Non-intuitive results of spectroscopic
      and structural studies showed that methyl substitution at the 3- and 5- positions
      of the pyrazolyl rings reduces the ligand field strength through steric effects
      whereas methyl substitution at the 4-position of the pyrazolyl rings increases
      the ligand field strength through inductive effects.

PMID- 21720642
TI  - Harnessing endogenous growth factor activity modulates stem cell behavior.
AB  - The influence of specific serum-borne biomolecules (e.g. heparin) on growth
      factor-dependent cell behavior is often difficult to elucidate in traditional
      cell culture due to the random, non-specific nature of biomolecule adsorption
      from serum. We hypothesized that chemically well-defined cell culture substrates
      could be used to study the influence of sequestered heparin on human mesenchymal
      stem cell (hMSC) behavior. Specifically, we used bio-inert self-assembled
      monolayers (SAMs) chemically modified with a bioinspired heparin-binding peptide
      (termed "HEPpep") and an integrin-binding peptide (RGDSP) as stem cell culture
      substrates. Our results demonstrate that purified heparin binds to HEPpep SAMs in
      a dose-dependent manner, and serum-borne heparin binds specifically and in a dose
      dependent manner to HEPpep SAMs. These heparin-sequestering SAMs enhance hMSC
      proliferation by amplifying endogenous fibroblast growth factor (FGF) signaling,
      and enhance hMSC osteogenic differentiation by amplifying endogenous bone
      morphogenetic protein (BMP) signaling. The effects of heparin-sequestering are
      similar to the effects of supraphysiologic concentrations of recombinant FGF-2.
      hMSC phenotype is maintained over multiple population doublings on heparin
      sequestering substrates in growth medium, while hMSC osteogenic differentiation
      is enhanced in a bone morphogenetic protein-dependent manner on the same
      substrates during culture in osteogenic induction medium. Together, these
      observations demonstrate that the influence of the substrate on stem cell
      phenotype is sensitive to the culture medium formulation. Our results also
      demonstrate that enhanced hMSC proliferation can be spatially localized by
      patterning the location of HEPpep on the substrate. Importantly, the use of
      chemically well-defined SAMs in this study eliminated the confounding factor of
      random, non-specific biomolecule adsorption, and identified serum-borne heparin
      as a key mediator of hMSC response to endogenous growth factors.

PMID- 21720643
TI  - Unexpected formation of a trinuclear complex containing a Ta(IV)-Ta(IV) bond in
      the reactions of Bu(t)N=Ta(NMe2)3 with silanes.
AB  - A new trinuclear species containing a Ta(IV)-Ta(IV) bond, Ta(3)(MU-H)(MU
      NMe(2))(MU=NBu(t))(2)(=NBu(t))(NMe(2))(5), has been formed by reductive
      elimination of H(2). Ta(2)H(2)(MU-NMe(2))(2)(NMe(2))(2)(=NBu(t))(2) has also been
      isolated. O(2) oxidizes the Ta(IV)-Ta(IV) bond to yield Ta(3)(MU(3)
      O)(H)(MU=NBu(t))(MU-NMe(2))(2)(NMe(2))(4)(=NBu(t))(2) under ligand exchange.
      Delocalization of d electrons is discussed.

PMID- 21720644
TI  - Para-hydrogen induced polarization of amino acids, peptides and deuterium
      hydrogen gas.
AB  - Signal Amplification by Reversible-Exchange (SABRE) is a method of
      hyperpolarizing substrates by polarization transfer from para-hydrogen without
      hydrogenation. Here, we demonstrate that this method can be applied to
      hyperpolarize small amounts of all proteinogenic amino acids and some chosen
      peptides down to the nanomole regime and can be detected in a single scan in low
      magnetic fields down to 0.25 mT (10 kHz proton frequency). An outstanding feature
      is that depending on the chemical state of the used catalyst and the investigated
      amino acid or peptide, hyperpolarized hydrogen-deuterium gas is formed, which was
      detected with (1)H and (2)H NMR spectroscopy at low magnetic fields of B(0) = 3.9
      mT (166 kHz proton frequency) and 3.2 mT (20 kHz deuterium frequency).

PMID- 21720645
TI  - Biofunctionalization of electrowetting-on-dielectric digital microfluidic chips
      for miniaturized cell-based applications.
AB  - In this paper we report on the controlled biofunctionalization of the hydrophobic
      layer of electrowetting-on-dielectric (EWOD) based microfluidic chips with the
      aim to execute (adherent) cell-based assays. The biofunctionalization technique
      involves a dry lift-off method with an easy to remove Parylene-C mask and allows
      the creation of spatially controlled micropatches of biomolecules in the Teflon
      AF((r)) layer of the chip. Compared to conventional methods, this method (i) is
      fully biocompatible; and (ii) leaves the hydrophobicity of the chip surface
      unaffected by the fabrication process, which is a crucial feature for digital
      microfluidic chips. In addition, full control of the geometry and the dimensions
      of the micropatches is achieved, allowing cells to be arrayed as cell clusters or
      as single cells on the digital microfluidic chip surface. The dry Parylene-C lift
      off technique proves to have great potential for precise biofunctionalization of
      digital microfluidic chips, and can enhance their use for heterogeneous bio
      assays that are of interest in various biomedical applications.

PMID- 21720646
TI  - Effects of external electric fields on double proton transfer kinetics in the
      formic acid dimer.
AB  - Molecules can be exposed to strong local electric fields of the order of 10(8)
      10(10) V m(-1) in the biological milieu. The effects of such fields on the rate
      constant (k) of a model reaction, the double-proton transfer reaction in the
      formic acid dimer (FAD), are investigated. The barrier heights and shapes are
      calculated in the absence and presence of several static homogenous external
      fields ranging from 5.14 * 10(8) to 5.14 * 10(9) V m(-1) using density functional
      theory (DFT/B3LYP) and second order Moller-Plesset perturbation theory (MP2) in
      conjunction with the 6-311++G(d,p) Pople basis set. Conventional transition state
      theory (CTST) followed by Wigner tunneling correction is then applied to estimate
      the rate constants at 25  degrees C. It is found that electric fields parallel to
      the long axis of the dimer (the line joining the two carbon atoms) lower the
      uncorrected barrier height, and hence increase the raw k. These fields also
      flatten the potential energy surface near the transition state region and, hence,
      decrease the multiplicative tunneling correction factor. The net result of these
      two opposing effects is that fields increase k(corrected) by a factor of ca. 3-4
      (DFT-MP2, respectively) compared to the field-free k. Field strengths of ~3 *
      10(9) V m(-1) are found to be sufficient to double the tunneling-corrected double
      proton transfer rate constant at 25  degrees C. Field strengths of similar orders
      of magnitudes are encountered in the scanning tunneling microscope (STM), in the
      microenvironment of a DNA base-pair, in an enzyme active site, and in intense
      laser radiation fields. It is shown that the net (tunneling corrected) effect of
      the field on k can be closely fitted to an exponential relationship of the form k
      = aexp(bE), where a and b are constants and E the electric field strength.

PMID- 21720647
TI  - The relationship between photocatalytic activity and photochromic state of
      nanoparticulate silver surface loaded titanium dioxide thin-films.
AB  - Anatase titania thin-films were prepared by a modified spray-pyrolysis method.
      Glass substrates were coated at room temperature with an aerosol-spray of a
      titania sol-gel solution and then annealed at 500  degrees C to form rough,
      transparent, crystalline thin-films of anatase TiO(2). Silver nanoparticles were
      deposited on the surface of these films by a photo-assisted deposition method;
      films were dip-coated in methanolic solutions of silver nitrate salt and then
      photo-irradiated for 5 h with UVC light. The AgNO(3) concentration was adjusted
      to create an array of films with varying silver loadings. The films displayed
      photochromism; changing colour to orange-brown in UV-light to colourless under
      white light. The rates of photochromic change, when subjected to four different
      lighting conditions (UVC, UVA, white light and dark), were analysed by UV-visible
      spectroscopy. By assessing the photocatalytic activity to these light sources it
      was found that the initial photochromic state of the material had a profound
      effect on the films photocatalytic ability. This effect was more pronounced in
      the more concentrated silver loaded films; where significant enhancements in
      photoactivity occurred when reactions were initiated from the photo-reduced
      state. The mode of improved photocatalysis was attributed to the photo-generated
      electron trapping by silver nanoparticles, which stabilised photo-generated holes
      and drove photo-oxidation processes. We believe this is the first study in which
      the relationship between the photochromic state of a thin-film and its subsequent
      photocatalytic activity is reported.

PMID- 21720648
TI  - An X-ray and neutron scattering study of the equilibrium between trimethylamine N
      oxide and urea in aqueous solution.
AB  - The interaction of the osmolytes trimethylamine N-oxide (TMAO) and urea in
      aqueous solutions at 40  degrees C was investigated by isotopic substitution
      neutron scattering at a TMAO mole fraction of 0.05 and TMAO/urea concentration
      ratios of 1 : 2 and 1 : 4. The partial pair distribution functions obtained by
      the empirical potential structure refinement method are consistent with those
      obtained previously for similar pure TMAO and 1 : 1 TMAO-urea solutions and
      indicate that urea progressively replaces the water molecules in the first
      coordination shell of the TMAO oxygen atom. The apparent association constant for
      the TMAO : urea complex (K(1)) was calculated to be 0.14 M(-1), which is of the
      same order as the experimental urea-protein binding constants per site reported
      in the literature. This confirms that the two osmolytes act independently at
      least in the physiological range.

PMID- 21720649
TI  - Diastereoselective radical mediated alkylation of a chiral glycolic acid
      derivative.
AB  - Radical alkylation of 2-(tert-butyl)-2-methyldioxolan-4-one, a chiral equivalent
      of glycolic acid, occurs with good to high diastereoselectivity that compares
      favorably with the corresponding enolate alkylation. The importance of the
      position of the transition state position, early or late, is highlighted.

PMID- 21720650
TI  - M2delta to ligand pi-conjugation: testbeds for current theories of mixed valence
      in ground and photoexcited states of molecular systems.
AB  - Redox active quadruply bonded units, M(2), can be combined so that they either
      (i) are bridged by an organic linker or (ii) function as a bridge between two
      identical organic ligands. When two M(2) units are linked together by an organic
      group that affords M(2)delta-bridge pi-conjugation the electronic structure of
      each M(2) unit is perturbed by the other in the ground state, the photoexcited
      states, and the mixed valence oxidized form. Similarly when a M(2) center links
      two organic pi systems represented by L, the two organic units are coupled by
      Lpi*-M(2)delta-Lpi* interactions in their ground state, their photoexcited
      states, and the mixed valence reduced state. The photoexcited states of the
      neutral complexes (both case i and ii) provide examples of excited state mixed
      valence. In case (i), the positive charge may be localized on one dinuclear
      center or may be delocalized over both M(2) units. Similarly in (ii), the
      electron may be localized on one ligand or delocalized over both. In this
      tutorial review, spectroscopic studies (UV-vis-NIR absorption, steady state
      emission, EPR, and time resolved infrared) of these mixed valence systems
      employing carboxylate tethers are described and the data are discussed in terms
      of contemporary theories of mixed valence ions.

PMID- 21720651
TI  - Multivalent glyconanoparticles with enhanced affinity to the anti-viral lectin
      Cyanovirin-N.
AB  - Low-mannose (LM) structures were coupled to gold nanoparticles (Au NPs) to
      amplify the affinity of LMs with Cyanovirin-N (CV-N) lectins and to study the
      structures of CV-N variants CVN(Q50C) and CVN(MutDB).

PMID- 21720652
TI  - Isotretinoin does not prolong QT intervals and QT dispersion in patients with
      severe acne: a surprising finding for a drug with numerous side effects.
AB  - BACKGROUND: Isotretinoin is a widely prescribed drug for the treatment of severe
      acne. Several adverse cardiac effects due to isotretinoin have been previously
      reported. However, no data exist on the effects of isotretinoin therapy on QT
      intervals. OBJECTIVE: To investigate the effects of isotretinoin therapy on QT
      intervals and QT dispersion, and also to see if it is related to serum lipids,
      homocysteine and lipoprotein (a) or not. METHODS: Forty-five patients with severe
      acne (mean age 21+/-6 years, range 14-38 years; 26 female) were included in the
      study. Twelve-lead surface electrocardiograms (ECGs) were acquired at three
      stages: before therapy and at the ends of the first and sixth months of 0.8
      mg/kg/day of isotretinoin therapy. Serum levels of triglycerides, total
      cholesterol, low density lipoprotein cholesterol, high density lipoprotein
      cholesterol, very low density lipoprotein cholesterol, homocysteine and
      lipoprotein (a) were also measured at the day of ECG recordings. Minimum and
      maximum QT intervals were measured and QT dispersion was calculated. RESULTS:
      Mean heart rates were similar throughout the isotretinoin therapy. Serum levels
      of lipids, homocysteine and lipoprotein (a) all increased significantly at the
      end of the first month and remained significantly elevated at the end of sixth
      month (P is less than 0.05 for both stages). QT intervals and QT dispersion did
      not differ significantly throughout the six months of isotretinoin therapy (P is
      greater than 0.05). CONCLUSIONS: In patients with severe acne, six months of 0.8
      mg/kg/day of isotretinoin therapy neither prolongs QT interval, nor increases QT
      dispersion. This effect is not related to blood lipids, homocysteine or
      lipoprotein (a) levels. Our findings indicate that from the point of polymorphic
      ventricular tachycardia risk, 0.8 mg/kg/day of isotretinoin therapy is a safe
      choice in acne treatment.

PMID- 21720653
TI  - A randomized, placebo-controlled, double-blind study to evaluate the efficacy of
      a citrus bioflavanoid blend in the treatment of senile purpura.
AB  - BACKGROUND: Senile purpura is a common, chronic skin condition affecting more
      than 10 percent of individuals over the age of 50. Despite being a benign
      condition, the continual development of purpura lesions in afflicted patients is
      frequently a source of significant visual and social concern. To date, there are
      no known effective treatments for this condition. OBJECTIVES: To evaluate the
      efficacy of a novel nutraceutical citrus bioflavonoid blend in improving the
      skin's appearance in patients with senile purpura. METHODS: A six-week,
      randomized, multicenter, placebo-controlled, double-blind study was conducted to
      determine whether a uniquely formulated, oral citrus bioflavonoid supplement
      could treat active lesions of senile purpura while preventing new lesions from
      arising. Seventy patients with senile purpura were enrolled and 67 completed the
      study. Subjects were randomized into two groups receiving either a citrus
      bioflavonoid blend or placebo medication, which was taken orally twice daily for
      six weeks. Clinical evaluations were performed by blinded investigators at two
      locations. RESULTS: A statistically significant reduction in the number of new
      purpura lesions in the skin area undergoing clinical study was documented. At the
      end of six weeks, the citrus bioflavonoid blend treated group showed a 50 percent
      reduction in purpura lesions from baseline. Patient self-assessment of the
      effectiveness of the medication echoed the results of an investigator global
      assessment with a statistically significant improvement in the skin's appearance
      noted by the patients receiving the active medication. No adverse effects were
      noted by either the patients or investigators. CONCLUSION: This new treatment
      appears to both safely and effectively diminish skin bruising in patients with
      senile purpura.

PMID- 21720654
TI  - Antibiotic resistance: an editorial review with recommendations.
AB  - Within a relatively short period of time after the first antimicrobial drugs were
      introduced, bacteria began exhibiting varying degrees of resistance. The
      excessive use (and abuse) of antibiotics in agriculture, and in both human and
      veterinary medicine, has played a critical causative role in the development of
      antibiotic resistance, which is now recognized as a global public health threat.
      Increasing concern over this issue should impact the practice of cutaneous
      medicine and surgery, as dermatologists can easily adopt new healthcare delivery
      patterns that might reduce the development of antibiotic resistance and still
      achieve acceptable treatment outcomes. Dermatologists should seriously consider
      any and all alternative therapies before committing to an extended course of
      antibiotic therapy for disease entities that are almost certainly not infectious.
      Conversely, dermatologists should carefully and closely adhere to dosage and
      duration recommendations when using antibiotics to treat a bona fide infectious
      disorder.

PMID- 21720655
TI  - A bilateral comparison study of pimecrolimus cream 1% and a topical medical
      device cream in the treatment of patients with atopic dermatitis.
AB  - Corticosteroids are the mainstay of therapy for atopic dermatitis, but long-term
      use is associated with adverse effects. We sought to evaluate the clinical
      efficacy of two steroid-sparing creams for atopic dermatitis. Twenty patients
      were enrolled in an investigator-blinded, bilateral comparison study. Patients
      applied pimecrolimus cream twice daily to a target lesion on one side of the body
      and also applied a topical medical device cream three times daily on a
      symmetrical target lesion on the opposite side of the body for four weeks.
      Clinical assessments including Physician Global Assessment (PGA), Target Lesion
      Symptom Score (TLSS), subject self-assessment and digital photography were
      performed at the baseline, 2 week, and 4 week visits. Seventy-five percent of
      patients (pimecrolimus, 15 of 20; topical medical device, 15 of 20) were rated
      "clear" (0) or "almost clear" (1) by PGA for both medications after four weeks.
      Percent improvement of the PGA from randomization for pimecrolimus cream and the
      topical medical device cream were 72.50 and 71.67 respectively (P=0.9283). PGA
      scores decreased significantly from baseline for both treatments (P=0.004).
      Overall, there was no statistically significant difference between treatment
      groups for PGA scores throughout the study (P=0.8236). No cutaneous side effects
      were noted. Our study was limited by a small sample size and lack of double
      blinding; however, both treatments were found to be safe and effective in
      treating atopic dermatitis over four weeks. Significant improvements were noted
      for all efficacy variables. In conclusion, a lipid-rich, non-steroidal, topical
      medical device cream was as effective in improving atopic dermatitis as
      pimecrolimus cream.

PMID- 21720656
TI  - A new body moisturizer increases skin hydration and improves atopic dermatitis
      symptoms among children and adults.
AB  - Moisturizers result in an increase of skin hydration and restoration of the skin
      barrier function and play a prominent role in the longterm management of atopic
      dermatitis (AD). Cetaphil RestoradermTM Moisturizer (CRM) contains novel
      ingredients specifically designed for AD, and its effects on skin hydration, skin
      barrier function and signs of AD were assessed in four studies, three of which
      were evaluator-blinded, randomized and intra-individual comparison trials. A
      single application of CRM induced significantly greater hydration than the
      untreated control for at least 24 hours (P is less than 0.001). After the skin
      was disrupted with 0.5% sodium dodecyl sulfate (SDS), applications of CRM led to
      a more rapid restoration of skin barrier function and maintained significantly
      greater skin hydration compared to the untreated control (both P is less than
      0.05). After four weeks of twice-daily CRM application among subjects with a
      history of AD, a significant decrease of itching/stinging scores compared to
      baseline was reported, as well as an improvement in the quality-of- life and a
      high level of satisfaction regarding the product. When CRM was used as an
      adjunctive treatment with topical steroid for four weeks among subjects with mild
      to-moderate AD, a more rapid decrease of overall disease severity was observed on
      days 7, 14 and 21 by the blinded investigator (P is less than 0.05), compared to
      steroid treatment alone. In summary, CRM is suitable for the specific needs of
      patients with AD and can be used either alone for long-term management or in
      adjunction with traditional treatment for both short and long-term disease
      control.

PMID- 21720657
TI  - Complementary antioxidant function of caffeine and green tea polyphenols in
      normal human skin fibroblasts.
AB  - The study of free radicals is particularly relevant in the context of human skin
      carcinogenesis and photoaging because of these oxidants' ability to induce DNA
      mutations and produce lipid peroxidation byproducts, including 4-hydroxy-2
      nonenal (HNE). Therefore, it is important to identify and evaluate agents with
      the ability to modulate intracellular free radicals and HNE. The purpose of this
      research is to investigate the ability of antioxidants green tea polyphenols
      (GTPs) and caffeine, alone and in combination, to modulate the hydrogen peroxide
      (H2O2)-induced upregulation of reactive oxygen species (ROS) free radicals and
      HNE in normal human skin fibroblast WS-1 cells in vitro. GTPs and caffeine were
      selected for evaluation because these compounds have demonstrated antioxidative
      properties in various skin models. Furthermore, GTPs and caffeine share a close
      natural botanical association as caffeine is present in green tea, as well.
      Hydrogen peroxide is a well-known generator of free radicals that is produced
      during endogenous and UV-induced oxidation processes in human skin and was used
      to upregulate ROS and HNE in normal human fibroblast WS-1 cells. Using a flow
      cytometry-based assay, the results demonstrate that at 0.001% concentration,
      green tea polyphenols alone, and in combination with 0.1 mM caffeine, inhibited
      the upregulation of H2O2-generated free radicals and HNE in human skin
      fibroblasts in vitro. Caffeine alone demonstrated limited anti-oxidant
      properties.

PMID- 21720658
TI  - Corrugator supercilii muscle terminal nerve ablation using a novel thread
      technique for the treatment of hyperdynamic vertical glabellar furrows.
AB  - BACKGROUND: A novel percutaneous corrugator supercilii muscle terminal nerve
      CSMTN ablation technique is proposed for the treatment of hyperdynamic vertical
      glabellar furrows (HVGF). TECHNIQUE: Two surgical marks are placed on each
      eyebrow. One is placed at the level of the lateral canthus and the second at the
      outer border of the limbus. At each of the four marks, the following steps are
      carried out: (1) a guiding needle is used to punch the frontal skin at 3 mm above
      the eyebrow (orifice A) and will then travel deeply at the level of the
      supraperiostium and emerge outside the skin 3 mm below the eyebrow (orifice B) at
      the palpebral skin; (2) the needle is then reentered exactly at orifice B and
      will travel underneath the skin at a more superficial level in the subcutaneous
      layer and then emerge outside exactly at orifice A. Both ends of the thread are
      gently pulled in a sawing motion with counter tension until no more resistance is
      felt from the anatomical structures involved, and then the loops of thread are
      withdrawn from orifice A. RESULTS: Forty-seven subjects underwent bilateral CSMTN
      ablation. In the first 10 cases, the authors performed only one neurotomy per eye
      and observed a 50 percent HVGF recurrence rate. Then, the authors chose to
      perform two neurotomies per side and had a three percent recurrence rate (1/37)
      with a high degree of patient satisfaction. Major complications such as deforming
      hematomas, eyelid ptosis, abscess, scar formation or adhesions were not observed
      during follow up. CONCLUSION: This novel technique may represent a simple and
      permanent solution for HVGF.

PMID- 21720659
TI  - Medication choice and associated health care outcomes and costs for patients with
      acne and acne-related conditions in the United States.
AB  - BACKGROUND: Acne is a common condition for which multiple treatment options are
      available. The patterns of pharmacotherapy for acne and similar conditions, and
      the effect of those patterns on cost, are not well characterized. OBJECTIVE: This
      study examined the impacts of patient demographics and medication choices on
      patients' health status and associated medication costs. METHODS: A retrospective
      cross-sectional study was conducted using the 2007 Medical Expenditure Panel
      Survey (MEPS) database. Information on patient demographics, health status,
      medication utilization and medication costs was obtained from the database
      representing 3,784,816 patients with acne and similar conditions. RESULTS:
      Weighted multiple linear regression analyses indicated that the use of topical
      retinoids was preferred in combination with other treatments rather than as
      monotherapy. Oral antibiotics were widely prescribed and their use was associated
      with a significant decrease in total annual prescription spending. Use of oral
      retinoids and oral contraceptives increased the annual prescription costs
      significantly. Increase in annual drug refills was not associated with the
      improvement in health status. CONCLUSION: We observed an association with
      medication choice for acne and acne-related conditions on medication spending.
      Pharmacologic treatment of acne significantly adds to acne-related annual
      healthcare costs compared to non-pharmacologic treatment.

PMID- 21720660
TI  - Acitretin in dermatology: a review.
AB  - INTRODUCTION: Acitretin is a systemic retinoid drug used in the treatment of
      severe psoriasis. It has also been used for a spectrum of other difficult-to
      treat dermatoses, including hyperkeratotic and inflammatory dermatoses and non
      melanoma skin cancers. Here we review the available data regarding both FDA
      approved and off-label uses of acitretin, clinically relevant adverse events,
      precautions and monitoring. METHODS: A PubMed literature search was conducted
      utilizing the search term "acitretin," which yielded 714 hits. Results were
      further limited to English language clinical trials in human subjects. Of 78
      articles evaluated for relevance, 60 were included for review. RESULTS: Acitretin
      is effective as monotherapy and in multidrug therapeutic regimens for the
      treatment of psoriasis and other hyperkeratotic and inflammatory disorders, as
      well as for malignancy chemoprevention. Its use is limited by its teratogenic
      potential and other adverse effects, including mucocutaneous effects and
      hepatotoxicity. Potential adverse effects may be reduced or avoided by using
      lower doses of acitretin or in combination with other therapies. LIMITATIONS: The
      reviewed studies include many small trials and case reports of the use of
      acitretin for psoriasis. Studies of acitretin therapy for the treatment of other
      cutaneous disorders are limited. CONCLUSION: Acitretin is a beneficial treatment
      for psoriasis, and should be considered when not contraindicated. Particularly
      when used in combination with ultraviolet (UV) phototherapy, is a safe and cost
      effective therapeutic strategy.

PMID- 21720661
TI  - Clinical evidence for the role of a topical anti-inflammatory agent in comedonal
      acne: findings from a randomized study of dapsone gel 5% in combination with
      tazarotene cream 0.1% in patients with acne vulgaris.
AB  - BACKGROUND: Acne pathogenesis is multifactorial and includes inflammation.
      Combining drugs targeting multiple components of acne pathogenesis is standard
      practice. OBJECTIVE: To assess the safety and efficacy of dapsone gel 5%, an anti
      inflammatory agent, in combination with tazarotene cream 0.1% for treatment of
      acne vulgaris. METHODS: Patients were randomized to receive combination therapy
      (dapsone gel 5% twice-daily plus tazarotene cream 0.1% daily) or monotherapy
      (tazarotene cream 0.1% daily). Efficacy and safety data were collected after 1,
      2, 4, 8, and 12 weeks of treatment. RESULTS: Patients in both arms (n=86, dapsone
      + tazarotene; n=85, tazarotene) showed significant reductions from baseline in
      inflammatory, noninflammatory and total lesion counts (P is less than .001 for
      all). At 12 weeks, patients treated with dapsone plus tazarotene showed a greater
      reduction from baseline in noninflammatory (comedonal) and total lesion counts
      than tazarotene-treated patients (noninflammatory, 59.7 percent vs. 46.5 percent,
      P=.01; total, 63.3% vs. 53.6%, P=.02). The percentage of patients achieving
      treatment success (an investigator subjective score of 0 [none] or 1 [minimal])
      was greater in dapsone plus tazarotene?treated patients (42.2%) than in
      tazarotene-treated patients (21.8%;P=.01). Both treatments were well tolerated.
      CONCLUSION: Combination therapy with dapsone gel 5% plus tazarotene cream 0.1%
      was more effective than tazarotene monotherapy for treatment of comedonal acne.
      The results suggest that anti-inflammatory agents such as dapsone can effectively
      treat early stages of acne (both comedonal and noncomedonal) when used in
      combination with a retinoid.

PMID- 21720662
TI  - Decrease of insulin growth factor-1 as a novel mechanism for anti-androgen effect
      of isotretinoin and its reported association with depression in some cases.
AB  - Isotretinoin and its desirable effects have received tremendous attention in
      recent years by scientists. This article reviews the evidence that decrease of
      insulin growth factor-1 is implicated as a novel mechanism of anti androgenic
      effect and its reported association with depression in some cases.

PMID- 21720663
TI  - Novel treatment of female-pattern androgenetic alopecia with injected bimatoprost
      0.03% solution.
AB  - Female-pattern androgenetic alopecia is a very common disorder that has been
      associated with extreme psychological morbidity. Few treatments have documented
      utility and many physicians are often overwhelmed with how little is
      pharmacologically available to treat this condition. Novel treatments that are
      effective, safe, less costly and simple are in high demand. We report a case of
      female-pattern androgenetic alopecia that failed to respond to a novel treatment
      with injected bimatoprost solution. Hypothetically, the treatment should have
      been effective and although we did not have success, this report suggests
      critical points to consider in the future of prostaglandin analogs, as well as
      other therapies being considered for the treatment of female-pattern hair loss.

PMID- 21720664
TI  - Tamoxifen-induced hirsutism.
AB  - Tamoxifen, a triphenylethylethylene, is an adjuvant therapy used for the
      treatment of oestrogen-receptor positive breast carcinoma due to its oestrogen
      receptor antagonist effect.1 We report here a case of rapid onset of hirsutism
      following administration of tamoxifen.

PMID- 21720665
TI  - Fixed drug eruption associated with intravenous contrast media: report in a woman
      receiving iohexol.
AB  - Fixed drug eruption, a medication-associated mucocutaneous reaction, rarely
      presents as a delayed adverse reaction to intravenous non-ionic contrast media.
      We describe a 57-year-old woman with a history of metastatic renal cell carcinoma
      who repeatedly developed a sharply demarcated, erythematous patch on her left
      breast after receiving the iodinated non-ionic contrast media iohexol for staging
      computed tomography scans. Recurrent fixed drug eruption may be avoided by using
      another contrast medium. Prophylactic treatment with systemic corticosteroids may
      prevent repeated fixed drug eruption if an alternative contrast agent cannot be
      used.

PMID- 21720666
TI  - Dermal melanoma in a transplant patient.

PMID- 21720667
TI  - Merkel cell carcinoma: banal-appearing, aggressive actor.
AB  - Merkel cell carcinoma is a rare but often deadly cutaneous malignancy. It carries
      a 40 percent five-year mortality rate, in contrast to 15 percent for malignant
      melanoma, and the incidence is increasing among older and immunosuppressed
      patients. Dermatologists need to be aware of the particular diagnostic and
      treatment challenges as the incidence increases. New data is helping to identify
      patients most at risk, accurately stage the tumor and to optimize treatment
      regimens. With the recent discovery of a virus as part of the etiology of this
      tumor, approaches to use the body's immune system to attack the tumor have
      potential to significantly increase survival rates in the future. Merkel Cell
      carcinoma (MCC) is a rare but aggressive cutaneous malignancy. Its aggressive
      behavior, combined with its asymptomatic clinical presentation, means that tumors
      are often allowed to grow and spread before detection. As the tumor becomes
      better characterized and its etiology better understood, research is rapidly
      advancing in both pathogenesis and treatment. Since the discovery of a viral
      etiology for this tumor in 2008, progress is advancing rapidly.

PMID- 21720668
TI  - 2011 update on pancreas transplantation: comprehensive trend analysis of 25,000
      cases followed up over the course of twenty-four years at the International
      Pancreas Transplant Registry (IPTR).
AB  - AIM: This study aimed to analyze the outcome of pancreas and pancreas-kidney
      transplantations based on the comprehensive follow-up data reported to the
      International Pancreas Transplant Registry (IPTR). METHODS: As of December 2010,
      more than 35,000 pancreas transplantations have been reported to the IPTR: more
      than 24,000 transplantations in the US and more than 12,000 outside the US. Cases
      with follow-up information until March 2011 were included in the analysis.
      RESULTS: Pancreas transplantations in diabetic patients were divided into 3
      categories: those performed simultaneously with a kidney (SPK) (75%), those given
      after a previous kidney transplantation (PAK) (18%), and pancreas transplantation
      alone (PTA) (7%). The total number of pancreas transplantations steadily
      increased until 2004 but has since declined. The largest decrease was seen in
      PAK, which decreased by 50% from 2004 through 2010. Comparatively, the number of
      SPK decreased by 7% during this time. Era analysis of US transplantations between
      1987 and 2010 showed changes in recipient and donor characteristics. Recipient
      age at transplantation increased significantly as well as transplantations in
      type 2 diabetes patients. The trend over time was towards tighter donor criteria.
      There was a concentration on younger donors, preferable trauma victims, with
      short preservation time. Surgical techniques for the drainage of the pancreatic
      duct changed over time, too. Now enteric drainage is the predominantly used
      technique in combination with systemic drainage of the venous effluent of the
      pancreas graft. Immunosuppressive protocols developed towards antibody induction
      therapy with tacrolimus and MMF as maintenance therapy. The rate of
      transplantations with steroid avoidance increased over time in all 3 categories.
      These changes have led to improved patient and graft survival. Patient survival
      now reaches over 95% at one year post-transplant and over 83% after 5 years. The
      best graft survival was found in SPK with 86% pancreas and 93% kidney graft
      function at one year. PAK pancreas graft function reached 80%, and PTA pancreas
      graft function reached 78% at one year. In all 3 categories, early technical
      graft loss rates decreased significantly to 8-9%. Likewise, the 1-year
      immunological graft loss rate also decreased: in SPK, the immunological 1-year
      graft loss rate was 1.8%, in PAK 3.7%, and in PTA 6.0%. CONCLUSIONS: Patient
      survival and graft function improved significantly over the course of 24 years of
      pancreas transplantation in all 3 categories. With further reduction in surgical
      complications and improvements in immunosuppressive protocols, pancreas
      transplantation offers excellent outcomes for patients with labile diabetes.

PMID- 21720669
TI  - Pancreas transplantation: lessons learned from a decade of experience at Wake
      Forest Baptist Medical Center.
AB  - This article reviews the outcome of pancreas transplantations in diabetic
      recipients according to risk factors, surgical techniques, and immunosuppression
      management that evolved over the course of a decade at Wake Forest Baptist
      Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte
      globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT)
      at our institution demonstrated lower rates of acute rejection and infection in
      the alemtuzumab group. Consequently, alemtuzumab induction has been used
      exclusively in all pancreas transplantations since February 2009. Early steroid
      elimination has been feasible in the majority of patients. Extensive experience
      with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is
      described. Surveillance pancreas biopsy-directed immunosuppression has
      contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT
      recipients at our center, in contrast to recent registry reports of persistently
      higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact
      of donor and recipient selection on outcomes is explored. Excellent results have
      been achieved with older (extended) donors and recipients, in recipients of
      organs from donation after cardiac death donors managed with extracorporeal
      support, and in African-American patients. Type 2 diabetics with detectable C
      peptide levels have been transplanted successfully with outcomes comparable to
      those of insulinopenic diabetics. Our experiences are discussed in the light of
      findings reported in the literature.

PMID- 21720670
TI  - Current perspectives on laparoscopic robot-assisted pancreas and pancreas-kidney
      transplantation.
AB  - Pancreas transplant recipients continue to suffer high surgical morbidity.
      Current robotic technology provides a unique opportunity to test whether
      laparoscopy can improve the post-operative course of pancreas transplantation
      (PT). Current knowledge on robotic pancreas and renal transplantation was
      reviewed to determine feasibility and safety of robotic PT. Information available
      from literature was included in this review, together with personal experience
      including three PT, and two renal allotransplants. As of April 2011, the relevant
      literature provides two case reports on robotic renal transplantation. The
      author's experience consists of one further renal allotransplantation, two
      solitary PT, and one simultaneous pancreas-kidney transplantation. Information
      obtained at international conferences include several other renal
      allotransplants, but no additional PT. Preliminary data show that PT is feasible
      laparoscopically under robotic assistance, but raises concerns regarding the
      effects of increased warm ischemia time on graft viability. Indeed, during
      construction of vascular anastomoses, graft temperature progressively increases,
      since maintenance of a stable graft temperature is difficult to achieve
      laparoscopically. There is no proof that progressive graft warming produces
      actual damage to transplanted organs, unless exceedingly long. However, this
      important question is likely to elicit a vibrant discussion in the transplant
      community.

PMID- 21720671
TI  - The IKEM pancreas and islet transplant program as part of healthcare for type 1
      diabetes patients: retrospective analysis of outcome from 1983 to 2010.
AB  - Currently, 25-30 pancreas transplantations per year are carried out in type 1
      diabetes (T1D) recipients residing in Czech Republic. Most of the recipients are
      transplanted together with kidney allografts, but pancreas is also transplanted
      alone in selected patients with brittle diabetes. Since 2005, the Institute for
      Clinical and Experimental Medicine (IKEM) islet transplant program was initiated
      as complementary therapeutic modality. The aim of this paper was to analyze the
      transplant program at our clinical center, and to examine the survival of
      recipients, and their pancreas, kidney, and islet grafts. Patient and graft
      survival rates were evaluated in the following three categories using Kaplan
      Meier test: simultaneous pancreas and kidney transplantation (SPKTx), pancreas
      transplantation alone (PTA), and islet transplantation (ITx). Three hundred and
      ninety SPKTx, 34 PTA and 44 ITx were carried out between 1983 and 2010. One- and
      5-year patient survival rates were 92 % and 81% in SPKTx, respectively. In SPKTx,
      the 1-year survival rate of pancreas grafts was 78%, and the 5-year rate was 66%.
      Kidney graft survival rates were 89% and 79%, respectively, after the same follow
      up periods. In the PTA category, recipient survivals were 100% after 1 year, and
      92% after 3 years. 70% and 65% of pancreatic grafts were working properly at 1
      and 3-year follow-ups, respectively. To date, we have carried out 44 islet
      transplantations in 31 recipients. Islet function (C-peptide >= 0.2 ng/ml) was
      documented in 60% of recipients after 12 months. So far, only 3 patients remained
      free of exogenous insulin. While SPKTx is a well established treatment for uremic
      T1D patients, ITx represents an emerging complementary treatment modality. The
      latter is especially suitable for high-risk recipients, but routine clinical
      application is still hampered by the limited availability of usable organ
      transplants and viability of transplanted islets.

PMID- 21720672
TI  - Risks and benefits of transplantation in the cure of type 1 diabetes: whole
      pancreas versus islet transplantation. A single center study.
AB  - BACKGROUND: Pancreas and islet transplantation are the only available options to
      replace beta-cell function in patients with type 1 diabetes. Great variability in
      terms of rate of success for both approaches is reported in the literature and it
      is difficult to compare the respective risks and benefits. OBJECTIVES: The aim of
      this study was to analyze risks and benefits of pancreas transplantation alone
      (PTA) and islet transplantation alone (ITA) by making use of the long-term
      experience of a single center where both transplantations are performed. We
      focused on the risks and benefits of both procedures, with the objective of
      better defining indications and providing evidence to support the decision-making
      process. The outcomes of 33 PTA and 33 ITA were analyzed, and pancreas and islet
      function (i.e., insulin independence), perioperative events, and long-term
      adverse events were recorded. RESULTS: We observed a higher rate of insulin
      independence in PTA (75%) versus ITA (59%), with the longer insulin independence
      among PTA patients receiving tacrolimus. The occurrence of adverse events was
      higher for PTA patients in terms of hospitalization length and frequency, re
      intervention for surgical and immunological acute complications, CMV
      reactivation, and other infections. CONCLUSIONS: In conclusion, these results
      support the practice of listing patients for PTA when the metabolic control and
      the progression of chronic complications require a rapid normalization of glucose
      levels, with the exception of patients with cardiovascular disease, because of
      the high surgical risks. ITA is indicated when replacement of beta-cell mass is
      needed in patients with a high surgical risk.

PMID- 21720675
TI  - Contributions by researchers of "Ciencia de Frontera" of the Chilean Academy of
      Sciences.

PMID- 21720673
TI  - Islet transplantation and encapsulation: an update on recent developments.
AB  - Human islet transplantation can provide good glycemic control in diabetic
      recipients without exogenous insulin. However, a major factor limiting its
      application is the recipient's need to adhere to life-long immunosuppression,
      something that has serious side effects. Microencapsulating human islets is a
      strategy that should prevent rejection of the grafted tissue without the need for
      anti-rejection drugs. Despite promising studies in various animal models, the
      encapsulated human islets so far have not made an impact in the clinical setting.
      Many non-immunological and immunological factors such as biocompatibility,
      reduced immunoprotection, hypoxia, pericapsular fibrotic overgrowth, effects of
      the encapsulation process and post-transplant inflammation hamper the successful
      application of this promising technology. In this review, strategies are
      discussed to overcome the above-mentioned factors and to enhance the survival and
      function of encapsulated insulin-producing cells, whether in islets or surrogate
      beta-cells. Studies at our center show that barium alginate microcapsules are
      biocompatible in rodents, but not in humans, raising concerns over the use of
      rodents to predict outcomes. Studies at our center also show that the
      encapsulation process had little or no effect on the cellular transcriptome of
      human islets and on their ability to function either in vitro or in vivo. New
      approaches incorporating further modifications to the microcapsule surface to
      prevent fibrotic overgrowth are vital, if encapsulated human islets or beta-cell
      surrogates are to become a viable therapy option for type 1 diabetes in humans.

PMID- 21720676
TI  - Sublethal concentrations of waterborne copper induce cellular stress and cell
      death in zebrafish embryos and larvae.
AB  - Copper is an essential ion that forms part of the active sites of many proteins.
      At the same time, an excess of this metal produces free radicals that are toxic
      for cells and organisms. Fish have been used extensively to study the effects of
      metals, including copper, present in food or the environment. It has been shown
      that different metals induce different adaptive responses in adult fish. However,
      until now, scant information has been available about the responses that are
      induced by waterborne copper during early life stages of fish. Here, acute
      toxicity tests and LC50 curves have been generated for zebrafish larvae exposed
      to dissolved copper sulphate at different concentrations and for different
      treatment times. We determined that the larvae incorporate and accumulate copper
      present in the medium in a concentration-dependent manner, resulting in changes
      in gene expression. Using a transgenic fish line that expresses enhanced green
      fluorescent protein (EGFP) under the hsp70 promoter, we monitored tissue-specific
      stress responses to waterborne copper by following expression of the reporter.
      Furthermore, TUNEL assays revealed which tissues are more susceptible to cell
      death after exposure to copper. Our results establish a framework for the
      analysis of whole-organism management of excess external copper in developing
      aquatic animals.

PMID- 21720677
TI  - Location matters: the endoplasmic reticulum and protein trafficking in dendrites.
AB  - Neurons are highly polarized, but the trafficking mechanisms that operate in
      these cells and the topological organization of their secretory organelles are
      still poorly understood. Particularly incipient is our knowledge of the role of
      the neuronal endoplasmic reticulum. Here we review the current understanding of
      the endoplasmic reticulum in neurons, its structure, composition, dendritic
      distribution and dynamics. We also focus on the trafficking of proteins through
      the dendritic endoplasmic reticulum, emphasizing the relevance of transport,
      retention, assembly of multi-subunit protein complexes and export. We
      additionally discuss the roles of the dendritic endoplasmic reticulum in synaptic
      plasticity.

PMID- 21720678
TI  - The balance between GMD and OFUT1 regulates Notch signaling pathway activity by
      modulating Notch stability.
AB  - The Notch signaling pathway plays an important role in development and
      physiology. In Drosophila, Notch is activated by its Delta or Serrate ligands,
      depending in part on the sugar modifications present in its extracellular domain.
      O-fucosyltransferase-1 (OFUT1) performs the first glycosylation step in this
      process, O-fucosylating various EGF repeats at the Notch extracellular domain.
      Besides its O-fucosyltransferase activity, OFUT1 also behaves as a chaperone
      during Notch synthesis and is able to down regulate Notch by enhancing its
      endocytosis and degradation. We have reevaluated the roles that O-fucosylation
      and the synthesis of GDP-fucose play in the regulation of Notch protein
      stability. Using mutants and the UAS/Gal4 system, we modified in developing
      tissues the amount of GDP-mannose-deshydratase (GMD), the first enzyme in the
      synthesis of GDP-fucose. Our results show that GMD activity, and likely the
      levels of GDP-fucose and O-fucosylation, are essential to stabilize the Notch
      protein. Notch degradation observed under low GMD expression is absolutely
      dependent on OFUT1 and this is also observed in Notch Abruptex mutants, which
      have mutations in some potential O-fucosylated EGF domains. We propose that the
      GDP-fucose/OFUT1 balance determines the ability of OFUT1 to endocytose and
      degrade Notch in a manner that is independent of the residues affected by
      Abruptex mutations in Notch EGF domains.

PMID- 21720679
TI  - Regulation of cell polarity by controlled proteolytic systems.
AB  - Epithelial and neuronal cells are highly asymmetric, with discrete regions
      responsible for different roles that underlie the generation of specific
      compartments within cells that are distinct in biochemical composition,
      structure, and morphology that ultimately lead to distinct functions. Controlled
      and specific molecular targeting and sorting have been studied to understand the
      generation of asymmetric domains inside cells. Recently, a new and complementary
      explanation has emerged to account for the generation of domains that are
      enriched by a subset of proteins or polarization determinants: local proteolysis.
      In this review, we discuss the most conspicuous proteolytic systems that may
      contribute to the generation of cell polarity, namely the ubiquitin-proteosome
      and the calpain systems. Specifically, we focus this review on two cellular
      processes that depend on the acquisition of cell polarity; cell migration and the
      establishment of an axon in a neuronal cell.

PMID- 21720680
TI  - Nanoinformatics: an emerging area of information technology at the intersection
      of bioinformatics, computational chemistry and nanobiotechnology.
AB  - After the progress made during the genomics era, bioinformatics was tasked with
      supporting the flow of information generated by nanobiotechnology efforts. This
      challenge requires adapting classical bioinformatic and computational chemistry
      tools to store, standardize, analyze, and visualize nanobiotechnological
      information. Thus, old and new bioinformatic and computational chemistry tools
      have been merged into a new sub-discipline: nanoinformatics. This review takes a
      second look at the development of this new and exciting area as seen from the
      perspective of the evolution of nanobiotechnology applied to the life sciences.
      The knowledge obtained at the nano-scale level implies answers to new questions
      and the development of new concepts in different fields. The rapid convergence of
      technologies around nanobiotechnologies has spun off collaborative networks and
      web platforms created for sharing and discussing the knowledge generated in
      nanobiotechnology. The implementation of new database schemes suitable for
      storage, processing and integrating physical, chemical, and biological properties
      of nanoparticles will be a key element in achieving the promises in this
      convergent field. In this work, we will review some applications of
      nanobiotechnology to life sciences in generating new requirements for diverse
      scientific fields, such as bioinformatics and computational chemistry.

PMID- 21720681
TI  - Contribution of dendritic cell/T cell interactions to triggering and maintaining
      autoimmunity.
AB  - Under healthy conditions, there is a balance between tolerance to self-tissue
      constituents and immunity against foreign antigens. Autoimmunity diseases (AD)
      take place when that equilibrium is disrupted and the immune response is directed
      to self-antigens, leading to injury or destruction of host tissues. The
      mechanisms conducing to the loss of immune tolerance remain largely unknown. The
      recent appearance of biological therapies has contributed to significant
      reduction in morbidity. However, currently available therapies are associated
      with important side effects and work only as palliative treatments. Dendritic
      cells (DCs) have emerged as key players in developing and maintaining adaptive
      immunity due to their capacity to prime and modulate T cell function. Therefore,
      because DCs work as central modulators of immune tolerance, it is likely that
      alterations in their function can lead to the onset of autoimmune-inflammatory
      diseases. By modulating DC function, novel pathways in antigen-specific tolerance
      could be established. In this article, the possible contribution of altered DC-T
      cell interactions to the onset of autoimmunity are discussed. In addition, we
      expand on the notion that some of the functions of these cells could be relevant
      targets for intervening therapies aimed to restore the balance or even prevent
      the loss of tolerance.

PMID- 21720682
TI  - SHh activity and localization is regulated by perlecan.
AB  - Proliferation and cell fate determination in the developing embryo are
      extrinsically regulated by multiple interactions among diverse secreted factors,
      such as Sonic Hedgehog (SHh), which act in a concentration-dependent manner. The
      fact that SHh is secreted as a lipid-modified protein suggests the existence of a
      mechanism to regulate its movement across embryonic fields. We have previously
      shown that heparan sulfate proteoglycans (HSPGs) are required for SHh binding and
      signalling. However, it was not determined which specific HSPG was responsible
      for these functions. Here we evaluated the contribution of perlecan on SHh
      localization and activity. To understand the mechanism of action of perlecan at
      the cellular level, we studied the role of perlecan-SHh interaction in SHh
      activity using both cell culture and biochemical assays. Our findings show that
      perlecan is a crucial anchor and modulator of SHh activity acting as an
      extracellular positive regulator of SHh.

PMID- 21720683
TI  - Effects of shape variations on the energy metabolism of the sand cricket Gryllus
      firmus: a geometric morphometric analysis.
AB  - Respiration and energy metabolism are key processes in animals, which are
      severely constrained by the design of physical structures, such as respiratory
      structures. Insects have very particular respiratory systems, based on gas
      diffusion across tracheae. Since the efficiency of the tracheal respiratory
      system is highly dependent on body shape, the pattern of morphological variation
      during ontogeny could have important metabolic consequences. We studied this
      problem combining through-flow respirometry and geometric morphometrics in 88
      nymphs of the sand cricket, Gryllus firmus. After measuring production in each
      individual, we took digital photographs and defined eight landmarks for geometric
      morphometric analysis. The analysis suggested that ontogenic deformations were
      mostly related to enlargement of the abdomen, compared to thorax and head. We
      found that (controlling for body size) metabolic variables and especially resting
      metabolism are positively correlated with a shape-component associated to an
      elongation of the abdomen. Our results are in agreement with the mechanics of
      tracheal ventilation in orthopterans, as gas circulation occurs by changes in
      abdominal pressures due to abdominal contractions and expansions along the
      longitudinal axis.

PMID- 21720684
TI  - The physiological role of the unfolded protein response in plants.
AB  - Unfolded protein response (UPR) is a signaling mechanism activated by misfolded
      protein accumulation in the endoplasmic reticulum. It is a widespread process
      that has been described in organisms ranging from yeasts to mammals. In recent
      years, our understanding of UPR signaling pathway in plants has advanced. Two
      transcription factors from Arabidopsis thaliana have been reported to function as
      the sensor/ transducer of this response (AtbZIP60 and AtbZIP28). They seem to be
      involved in both heat and biotic stress. Furthermore, overexpression of one of
      them (AtbZIP60) produces plants with a higher tolerance for salt stress,
      suggesting that this transcription factor may play a role in abiotic stress.
      Furthermore, some data suggest that crosstalk between genes involved in abiotic
      stress and UPR may also exist in plants. On the other hand, UPR is related to
      programmed cell death (PCD) in plants given that that triggering UPR results in
      induction of PCD-related genes. This article reviews the latest progress in
      understanding UPR signaling in plants and analyzes its relationship to key
      processes in plant physiology.

PMID- 21720685
TI  - Are levels of digestive enzyme activity related to the natural diet in passerine
      birds?
AB  - Digestive capabilities, such as the rates nutrient hydrolysis and absorption, may
      affect energy intake and ultimately feeding behavior. In birds, a high diversity
      in gut biochemical capabilities seems to support the existence of a correlation
      between the morphology and physiology of the intestinal tract and chemical
      features of the natural diet. However, studies correlating the activity of
      digestive enzymes and the feeding habits at an evolutionary scale are scarce. We
      investigated the effect of dietary habits on the digestive physiological
      characteristics of eight species of passerine birds from Central Chile. The Order
      Passeriformes is a speciose group with a broad dietary spectrum that includes
      omnivorous, granivorous and insectivorous species. We measured the activity of
      three enzymes: maltase, sucrase and aminopeptidase-N. Using an autocorrelation
      analysis to remove the phylogenetic effect, we found that dietary habits had no
      effect on enzymatic activity. However, we found that granivorous and omnivorous
      species had higher levels of disaccharidase activities and insectivores had the
      lowest. The major difference in enzymatic activity found at the inter-specific
      level, compared to the reported lower magnitude of enzyme modulation owing to
      dietary acclimation, suggests that these differences to some extent have a
      genetic basis. However, the lack of a clear association between diet categories
      and gut physiology suggested us that dietary categorizations do not always
      reflect the chemical composition of the ingested food.

PMID- 21720686
TI  - New insights into the roles of megalin/LRP2 and the regulation of its functional
      expression.
AB  - Since the discovery of the low-density lipoprotein receptor (LDLR) and its
      association with familial hypercholesterolemia in the early 1980s, a family of
      structurally related proteins has been discovered that has apolipoprotein E as a
      common ligand, and the broad functions of its members have been described. LRP2,
      or megalin, is a member of the LDLR family and was initially called gp330.
      Megalin is an endocytic receptor expressed on the apical surface of several
      epithelial cells that internalizes a variety of ligands including nutrients,
      hormones and their carrier proteins, signaling molecules, morphogens, and
      extracellular matrix proteins. Once internalized, these ligands are directed to
      the lysosomal degradation pathway or transported by transcytosis from one side of
      the cell to the opposite membrane. The availability of megalin at the cell
      surface is controlled by several regulatory mechanisms, including the
      phosphorylation of its cytoplasmic domain by GSK3, the proteolysis of the
      extracellular domain at the cell surface (shedding), the subsequent intramembrane
      proteolysis of the transmembrane domain by the gamma-secretase complex, and
      exosome secretion. Based on the important roles of its ligands and its tissue
      expression pattern, megalin has been recognized as an important component of many
      pathological conditions, including diabetic nephropathy, Lowe syndrome, Dent
      disease, Alzheimer's disease (AD) and gallstone disease. In addition, the
      expression of megalin and some of its ligands in the central and peripheral
      nervous system suggests a role for this receptor in neural regeneration
      processes. Despite its obvious importance, the regulation of megalin expression
      is poorly understood. In this review, we describe the functions of megalin and
      its association with certain pathological conditions as well as the current
      understanding of the mechanisms that underlie the control of megalin expression.

PMID- 21720687
TI  - Finite size scaling in the local abundances of geographic populations.
AB  - We analyzed the statistical distribution of intra-specific local abundances for a
      set North American breeding bird species. We constructed frequency plots for
      every species and found that they showed long-tail power-law behavior, truncated
      at an upper abundance cut-off value. Based on finite size scaling arguments, we
      investigated whether frequency curves may be considered scaled copies of each
      other. Data collapse was possible after taking powers of the total abundance of
      each species, in order to correct deviations from the underlying universal finite
      size scaling function (UFSS). The UFSS power law exponent oscillated in time
      within the regime of unbounded variance, which is consistent with the wild
      fluctuations that characterize ecological phenomena. We speculate that our
      results may eventually be linked to other law-like macroecological phenomena,
      such as energetic constraints reported in allometric scaling.

PMID- 21720688
TI  - [Community antibiotic consumption in Chile, 2000-2008].
AB  - BACKGROUND: The Chilean Ministry of Health has implemented regulatory rules for
      the consumption of anti-biotics since September 1999, with sales restriction
      limited only with medical prescription. AIM: To analyze the impact of established
      regulatory measures from 2000 to 2008. MATERIAL AND METHODS: A retrospective
      analysis of antibiotics sales in pharmacies from 2000 to 2008 was performed. The
      information was obtained from the International Marketing System (IMS Health), an
      auditing system of pharmacy sales. The consumption unit used was the Defined
      Daily Dose per 1000 inhabitants/day (DDD). RESULTS: From 2000 to 2002 the
      regulatory rules had a great impact, but since 2002 the antibiotic consumption
      increased, especially amoxicillin, returning to similar leveis observed in 1998.
      CONCLUSIONS: The regulatory measures had an initial impact, but there was not
      reinforcement in the time and there was no further control. It is necessary to
      assume a permanent task and support of the authorities of health to educate the
      population about the implications of the inadequate use of antimicrobials and his
      effect on the microbial ecology.

PMID- 21720689
TI  - [Comparison of real-time polymerase chain reaction and antigenemia assay to
      detect cytomegalovirus in pediatric transplants].
AB  - BACKGROUND: Cytomegalovirus (CMV) infections are an important cause of morbidity
      and mortality in transplant recipient. To date, the antigenemia assay is the most
      used technique for diagnostic and management of CM V infections. However,
      quantification of CMV viral load by real time polymerase chain reaction (RT-PCR)
      has becoming the method of choice to detect CMV in a rapid, sensitive and
      specific manner. OBJECTIVE: To compare antigenemia and RT-PCR assays in the
      detection of CMV in blood sample from solid organ and bone marrow transplant
      (BMT) in children attended at the Dr. Luis Calvo Mackenna Hospital. METHODS: In a
      prospective study, we detect the presence of CMV in blood sample by RT-PCR and
      antigenemia assays. RESULTS: We analyzed 219 blood samples from 68 children
      subjected to kidney, liver and BMT. Out of 219 samples analyzed, 147 were
      negative and 33 were positive for CMV by both techniques. Thirty-seven samples
      were positive only by RT-PCR and 2 by antigenemia. Considering the antigenemia as
      a reference, RT-PCR shows 94%, 80%, 34% and 99% sensitivity, specificity,
      positive and negative predictive values, respectively. The kappa coefficient
      between both techniques was 0.528. CONCLUSION: Quantitative determination of CMV
      viral load by RT-PCR is a sensitive technique with excellent negative predictive
      value compared to antigenemia. Our results support the use of RT-PCR as a
      technique that might facilitate the diagnostic and treatment of active CMV
      infection in pediatric transplants.

PMID- 21720690
TI  - [Epidemiologial profile of invasive candidiasis in intensive care units at a
      university hospital].
AB  - Invasive candidiasis (IC) epidemiology has changed in critically ill patients and
      limited data are available in Chile. OBJECTIVE: To describe the epidemiological
      and microbiological profile of IC in critically ill patients. METHODS:
      Observational prospective study conducted from October 2001 to August 2003 in
      critically ill adults with suspected or confirmed IC. RESULTS: 53 patients met
      criteria for IC, finding 18 (33.9%) candidemias, 22 (41.5%) disseminated IC, and
      13 (24.5%) local IC. We identified 8 (44.4%) C. albicans and 10 (55.6%) non
      albicans Candida in candidemias. C. tropicalis was the predominant non-albicans
      species (27.7%). An 88.8 % of Candidas sp recovered in candidemias were
      fluconazole susceptible. Overall hospital mortality was 24.5%. Mortality in
      candidemia was significantly lower than in disseminated IC (16.6 vs 31.8%, p =
      0.02). CONCLUSIONS: A higher proportion of non-albicans Candida was observed in
      candidemias from critically ill patients. However, most of these strains were
      fluconazole susceptible. A lower overall mortality was observed in candidemias.

PMID- 21720691
TI  - [Invasive fungal disease in patients from five hospitals in the Valparaiso
      region, Chile: 2004 to 2009].
AB  - INTRODUCTION: Invasive fungal disease (IFD) is a frequent cause of morbidity and
      mortality in immuno-compromised patients. These infections are caused mainly by
      Candida albicans and Aspergillus fumigatus. OBJECTIVES: To describe IFD diagnosed
      by culture in adults and children from five hospitals in Valparaiso, Chile and to
      determine the species involved and the in vitro sensitivity oi Candida spp.
      MATERIAL AND METHODS: Biodemographical data, results of cultures, antifungal
      treatment and mortality after 30 days, was collected. The fungi were identified
      by standard methods and the sensitivity of the yeasts was obtained according to
      the M44-A CLSI document. RESULTS: Fifty one IFD were diagnosed, 13 in patients
      with haematological malignancies and 10 in immunocompetent patients from the
      adult ICU. The following fungal species were isolated: 34 yeasts, 15 filamentous
      fungi and 2 Histoplasma capsulatum. There were 33 proven and 1 probable IFD by
      yeasts. By filamentous fungi, there were 6 proven and 9 probable IFD, 13 out of
      15 isolated species were Aspergillus (A. fumigatus being the most frequent). C.
      albicans was the most frequent isolated yeast, followed by C. tropicalis and C.
      parapsilosis. All were sensitive to fluconazol and voriconazol, excepting C.
      glabrata. The mortality by Candida and by filamentous fungi was 42.42% and 86.66%
      respectively. CONCLUSIONS: IFD was diagnosed mainly in immunocompromised and
      adult ICU patients. The mortality rate in IFD by filamentous fungi was higher
      than Candida group. The main agents involved were Candida albicans and
      Aspergillus fumigatus. A high sensitivity to fluconazol and voriconazol was found
      in strains of Candida.

PMID- 21720692
TI  - [Update of the consensus document on ventilator-associated pneumonia: part I.
      Diagnostic aspects].
AB  - The best strategy to resolve the diagnosis of ventilator-associated pneumonia
      (VAP) is unsettled, and periodic reviews of new evidence are necessary. An update
      was performed to renew the 2001 recommendations on the diagnosis of this
      condition by The Chilean Society of Infectious Diseases. The main proposals are:
      to incorporate a microbiology-based strategy when there is a suspicion of VAP to
      gather local epidemiologic data and design appropriate empirical therapy for next
      cases, and to apply a non-invasive approach such as an endotracheal aspirate or
      mini-bronchoalveolar lavage, to facilitate accessibility and lower costs. There
      is no advantage on survival using either quantitative or qualitative cultures for
      VAP and a definite recommendation cannot be issued. Nonetheless, quantitative
      cultures are more specific and could facilitate to reject the diagnosis, look for
      other alternatives, and avoid unnecessary antibiotics. Biomarkers to assist VAP
      diagnosis are not recommended due to their poor performance. However, serial
      procalcitonin determinations have been useful to decrease antibiotic use in
      critical care patients and this biomarker has a better diagnostic yield than C
      reactive protein in this setting. This consensus also recommends discriminating
      VAP from ventilator-associated tracheobronchitis (VAT). The latter represents a
      separate entity characterized by an inflammatory response with purulent tracheal
      secretions but without new pulmonary infiltrates. Although preliminary data
      supports a beneficial effect of antibiotics to treat this condition, evidence is
      limited yet, and both conditions deserve to be discriminated (VAP versus VAT).

PMID- 21720694
TI  - [The travelling child: recommendations].

PMID- 21720695
TI  - [Aeromonas spp].

PMID- 21720696
TI  - [Phenotypic characteristics and virulence factors in Aeromonas strains isolated
      from patients with diarrheic disease in Cuba].
AB  - Fifty four strains of Aeromonas spp were isolated from patients with acute
      diarrheic episodes by using Aerokey II and Aeroesquema methods. In vitro
      antimicrobial susceptibility and virulence factors were analyzed. The most
      frequently isolated specie was Aeromonas caviae. Over 75% of strains exhibited
      resistance to penicillins and ce-phalosporins; for the other antibiotic groups
      resistance was under 20%. Twenty six strains (48.1 %) were multiresist-ant. At
      least one virulence factor among those evaluated in the study was present in 53
      (98.1%) of the 54 strains.

PMID- 21720697
TI  - [Adherence to immunizations in newborns less than 1500 gr at birth and/or younger
      than 32 weeks, in two chilean centers].
AB  - Preterm neonates less than 1500 gr. or younger than 32 weeks have an increased
      morbidity and mortality due to infectious diseases. Immunization of these
      children is critical but is often incomplete and delayed. OBJECTIVES: To describe
      the adherence of scheduled and additional vaccines recommended in preterms less
      than 1500 gr. and to compare the level of compliance in two centers. PATIENTS AND
      METHODS: Prematures less than 1500 gr. born between January 2006 and December
      2008 in a private center (HCPUC) and in a public health system (HSR) were
      included. Neonatal charts and follow up records were reviewed. Demographic data,
      diagnosis, scheduled vaccines, delays and its causes, prescription of additional
      vaccines were registered. RESULTS: 92 children were included in HCPUC and 246 in
      HSR. Among these 60-70% respectively had delayed immunizations. The reasons for
      these were considered not justified in almost 80% of the cases, being the primary
      reason oversight or lack of parental time. The use of additional vaccines is
      still low in both centers. CONCLUSIONS: Vaccination of prematures in Chile
      requires important improvements; education of healtheare personnel and parents,
      inclusion of modern computerized records and inclusion of new efficacious and
      safe vaccines in the regular immunization program with no cost to the patient.

PMID- 21720698
TI  - [Respiratory infections caused by metapneumovirus in elderly patients].
AB  - Human metapneumovirus infections are increasingly recognized among adult patients
      and the aim of this report is to present a series of 4 cases admitted during the
      winter of 2010. All were detected by direct fluorescence anti-bodies assay of
      respiratory samples and all were female patients with an age range of 79 to 95
      years, including two bedridden cases, one with dementia and three with chronic
      obstructive pulmonary disease. One patient presented with parainfluenza 3 virus
      coinfection. Patients presented with pneumonia in 3 cases (interstitial pattern
      in 2 and lobar consolidation in the other) or acute exacerbation of chronic
      bronchitis in the remaining case. Symptoms were present for 3 to 7 days before
      admission and 3 have wheezing. All had hypoxemic or global respiratory failure
      and lymphopenia (< 1.000/mm3). Hospitalization lasted for 5 to 20 days, marked in
      the 3 cases that survived by prolonged bronchial obstructive manifestations. Two
      cases required non invasive mechanical ventilation. Human metapneumovirus
      infections can decompensate elderly patients with chronic respiratory diseases
      generating hospital admission and a prolonged morbidity marked by obstructive
      manifestations and sometimes can become into death.

PMID- 21720699
TI  - [Erysipelas outbreaks in Chile].
AB  - Historical antecedents of erysipelas outbreaks in Chile, registered by national
      bibliography at years 1822 and 1873 are reviewed. The first one, after an
      earthquake, with numerous severe ataxo-adynamic manifestations and the second,
      more attenuated with few severe cases. Remembers of treatments utilized at XIX
      Century for the disease and the beginning of sulphamides prescription at the
      thirty decade are presented. Afterwards penicillin and other antimicrobial agents
      treatments were implemented. Finally, we comment the severe presentation of soft
      tissues streptococcal diseases that appeared in the end of XX Century.

PMID- 21720700
TI  - Induction of dopaminergic neuronal-like cells from CD44+ human amniotic fluids
      that are ameliorative to behavioral recovery in a Parkinson's disease rat model.
AB  - Parkinson's disease (PD) is a common age-associated neurodegenerative disorder.
      To date, stem cell transplantation therapy has been developed to replace lost or
      damaged neural cells in PD patients, in whom dopaminergic neuron cells are lost.
      Here, we show that CD44+ human amniotic fluid cells (HuAFCs) can be induced to
      become functional dopaminergic neuronal-like cells in vitro. Furthermore, when
      CD44+ or CD44- HuAFCs were transplanted into 6-hydroxydopamine (6-OHDA)-treated
      PD rats, the results indicated that CD44+ HuAFCs expressed multiple dopaminergic
      neuron cell markers and were ameliorative to behavioral recovery in PD rats after
      induction both in vitro and in vivo. CD44- HuAFCs did not fully differentiate
      into dopaminergic neuronal-like cells. When compared with CD44- HuAFCs, CD44+
      HuAFCs showed increased activity in regeneration of dopaminergic neuron cell-like
      cells, increased migration distances, and improvement of animal behavior in the
      PD rat model. Therefore, CD44+ HuAFCs could be a source of dopaminergic neuronal
      like cells with a potential use in cell-replacement therapy for PD.

PMID- 21720701
TI  - Capture of dengue virus type 3 using anionic polymer-coated magnetic beads.
AB  - Dengue virus (DENV) is a mosquito-borne virus and can be transmitted to humans by
      mosquito vectors. Although surveillance of dengue virus-infected mosquitoes is
      the most effective way of controlling DENV infections, detection of DENVs in
      mosquitoes is limited by the low sensitivity of available detection methods. We
      here report a method for capturing DENV type 3 (DENV-3) from mosquito cells using
      magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic
      anhydrate). The beads were incubated with cell culture medium of DENV-3-infected
      mosquito cells, then separated from the supernatant by applying a magnetic field
      and washed. Adsorption of DENV-3 on the beads was confirmed by reverse
      transcription-polymerase chain reaction, which detected the presence of DENV-3
      genomic RNA on the beads, and Western blotting, which determined the major DENV-3
      envelope protein on the beads. Therefore, this capture method may enable an
      improvement in DENV-3 detection.

PMID- 21720702
TI  - Involvement of calmodulin and actin in directed differentiation of rat cortical
      neural stem cells into neurons.
AB  - Calmodulin (CaM) is a multifunctional receptor of intercellular Ca2+, which under
      different physiological conditions or at different developmental stages plays
      different roles in different tissues and cells. This study aimed to investigate
      the involvement of spatial expression and coexistence of CaM and actin in
      directed differentiation of rat cortical neural stem cells (NSCs) into neurons.
      Immunohistochemistry, RT-PCR and immunofluorescence dual-labeling technology was
      conducted to investigate the temporal and spatial pattern of CaM and actin
      proteins in neuron-oriented cortical NSC differentiation. Confocal laser scanning
      microscopy (CLSM) was used to observe changes of the coexistence in protein
      expression. Our results showed that cortical NSCs expressed and showed localized
      CaM and actin in a well-defined temporal order. In the process of rat neuron
      oriented cerebral cortical NSC differentiation, CaM displayed a similar
      expression pattern with actin in the development of neurons, that is, both
      proteins extended into neurites following the sprouting and growth of neurons.
      These results suggest that the temporal and spatial pattern of CaM and actin
      expression is comparable to the growth of cell processes in differentiating NSCs.
      Therefore, both CaM and actin may jointly participate in the development and
      maturation of neurites, and this provides a theoretical basis for further study
      of the biological features of neuron-oriented NSC differentiation.

PMID- 21720703
TI  - Inability of NCoR/SMRT to repress androgen receptor transcriptional activity in
      prostate cancer cell lines.
AB  - The molecular mechanisms leading to castration-resistant prostate cancer (CRPC)
      are poorly understood. Among several mechanisms leading to CRPC growth a
      dysregulation of androgen receptor (AR) co-regulators (i.e. up-regulation of co
      activators or down-regulation of co-repressors) is discussed. There are numerous
      reports demonstrating an increased expression of co-activators during prostate
      cancer progression. On the contrary, the impact of co-repressors on tumor growth
      and development is less clear. In this study we compared the effects of two known
      co-repressors, NCoR and SMRT, on AR transcriptional activity in prostate cancer
      (PCa) cell lines and compared them to that in COS-1 cells. Interestingly, we
      found that NCoR/SMRT overexpression did not repress AR-dependent gene expression
      in the PCa cell lines, but rather activated it. This finding is probably due to
      an impaired AR-co-repressor interaction in the prostate cancer cell lines. In
      conclusion, we provide evidence that up-regulation of NCoR or SMRT may increase
      transcriptional activity of the AR in a cell type-specific context.

PMID- 21720704
TI  - Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell
      lung cancer: results from a phase III randomized multicentric trial.
AB  - Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell
      mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase
      III randomized multicenter trial was conducted to evaluate the impact of
      subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall
      survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically
      confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization
      on the basis of center, ECOG PS, stage of disease and percentage of weight loss.
      Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100
      mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm].
      In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000
      IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute
      increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of
      12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease
      was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT
      arms, respectively. No differences in response were found in any subgroup
      analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2
      arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival
      was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log
      rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most
      common grade >=3 adverse events were gastrointestinal toxicity (mainly nausea and
      diarrhea) and myelosuppression. No relevant differences in clinical outcome were
      observed from the addition of IL-2 to CT. Future studies investigating the role
      of T-regulators in chemoimmunotherapeutic regimens could be performed.

PMID- 21720705
TI  - Lentiviral short hairpin RNA screen of human kinases and phosphatases to identify
      potential biomarkers in oral squamous cancer cells.
AB  - Oral carcinoma is a serious public health problem and the leading cause of head
      and neck cancer mortality worldwide. Moreover, oral cancer patients often present
      symptoms at a late stage and show a high recurrence rate after treatment.
      Therefore, there is an urgent need to identify novel biomarkers for early
      diagnosis or clinical oral cancer therapy. In this study, we employed a subset of
      lentiviral short hairpin RNAs targeted against various kinases and phosphatases,
      designed by The RNAi Consortium, to screen systemically and in a high-throughput
      manner for potential growth regulators of oral cancer cells. The screen revealed
      a total of 50 candidate genes, for which more than 90% of growth inhibition in
      human oral squamous cancer HSC-3 cells was obtained. Furthermore, bioinformatic
      analysis of these candidate genes identified transforming growth factor-beta
      receptor type II- and fms-related tyrosine kinase 3-related molecular pathways
      that are involved in NF-kappaB-mediated growth of HSC-3 cells. These candidate
      genes may be potential biomarkers for early diagnosis of oral cancer. In
      addition, these candidate genes represent potential targets for anticancer drug
      design helping to develop a personalized treatment to combat oral cancer.

PMID- 21720706
TI  - Syntaxins 3 and 4 mediate vesicular trafficking of alpha5beta1 and alpha3beta1
      integrins and cancer cell migration.
AB  - Integrins, a family of heterodimeric receptors for cell adhesion to the
      extracellular matrix (ECM), play key roles in cell migration, cancer progression
      and metastasis. As transmembrane proteins, integrins are transported in vesicles
      and delivered to the cell surface by vesicular trafficking. The final step for
      integrin delivery, i.e., fusion of integrin-containing vesicles with the plasma
      membrane, is poorly understood at the molecular level. The SNARE (soluble N
      ethylmaleimide-sensitive factor attachment protein receptor) proteins syntaxins
      1, 2, 3 and 4 are present at the plasma membrane to drive vesicle fusion. In this
      study, we examined the roles of syntaxins 1, 2, 3 and 4 in vesicular trafficking
      of alpha5beta1 and alpha3beta1 integrins. We showed that syntaxins 2, 3 and 4
      were expressed in HeLa cervical adenocarcinoma cells and PANC-1 pancreatic
      adenocarcinoma cells. In migrating HeLa and PANC-1 cells, syntaxins 2, 3 and 4 co
      localized with the lipid raft constituent GM1 ganglioside at the leading edge.
      siRNA knockdown (KD) of syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells
      reduced cell surface expression of alpha5beta1 and alpha3beta1 integrins and
      accumulated the integrins in cytoplasmic vesicles, indicating that syntaxins 3
      and 4 mediate vesicular trafficking of alpha5beta1 and alpha3beta1 integrins to
      the cell surface. In addition, KD of syntaxins 3 and 4 inhibited cell adhesion to
      fibronectin, suppressed chemotactic cell migration and triggered apoptosis.
      Collectively, these data suggest that syntaxins 3- and 4-dependent integrin
      trafficking is important in cancer cell migration and survival, and may be a
      valuable target for cancer therapy.

PMID- 21720707
TI  - Expression of CLDN1 in colorectal cancer: a novel marker for prognosis.
AB  - Claudin1 (CLDN1) plays an important role not only in the intercellular barrier
      function of tight junctions (TJs) but also in migration and invasiveness of
      cancer cells. Previous reports show that CLDN1 overexpression is significantly
      related to the malignant behavior in several cancer types whereas its
      significance in colorectal cancer (CRC) is not fully understood. The present
      study comprised 119 patients who underwent surgery for CRC, as well as 3 cell
      lines derived from human CRC. The correlation of gene expression with clinical
      parameters in patients was assessed by knockdown experiments using 3 cell lines.
      Patients with high CLDN1 expression were statistically shown to have a relatively
      better prognosis, and those with low CLDN1 expression showed poorer overall
      survival and disease-free survival than those with high expression. The
      assessment of CLDN1 knockdown in the 3 cell lines demonstrated that the siRNA
      inhibition resulted in a statistically significant increase in cell invasiveness.
      In conclusion, the present data strongly suggest that CLDN1 expression is a
      prognostic factor in CRC patients.

PMID- 21720708
TI  - P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis
      in chronic myeloid leukemia cells.
AB  - Overexpression of P-glycoprotein (Pgp/ABCB1) in tumor cells is associated with a
      classic phenotype of multidrug resistance (MDR). Moreover, some members of the
      inhibitor of apoptosis protein (IAP) family, such as survivin, contribute to an
      apoptosis-resistant phenotype, by inhibiting chemotherapy-induced cell death and
      promoting MDR. By using Western blotting, qRT-PCR, Annexin V and
      immunofluorescence assays we have demonstrated a relationship between Pgp and
      survivin in a prior sensitive chronic myeloid leukemia (CML) cell line (K562). A
      high dose of vincristine induced a concomitant overexpression of Pgp and
      survivin, which was associated with a low apoptotic index in the K562 cell line.
      In addition, we observed a cytoplasmic co-localization of Pgp and survivin,
      suggesting a functional association between these two proteins in apoptosis
      control by a common mechanism. In summary, our data suggest that Pgp and survivin
      should be analyzed in aggregate because they may have significant impact on drug
      resistance in CML cells.

PMID- 21720709
TI  - beta-catenin/Tcf-4 complex transcriptionally regulates AKT1 in glioma.
AB  - Increasing evidence suggests that interplays between Wnt/beta-catenin and
      PI3K/AKT signaling cascades are involved in tumor development and progression.
      However, the exact mechanism in glioma is not well known. Using aspirin, we found
      that the expression levels of AKT1 in glioma cells significantly correlated with
      the transcriptional activity of beta-catenin. Similar observations were made when
      we subjected glioma cells to treatment with Tcf4 siRNA. Moreover, both aspirin
      and Tcf4 siRNA can suppress the proliferation and induce apoptosis of glioma. In
      addition, our analysis of the gene promoter of AKT1 revealed multiple putative
      Tcf-4 binding sites. In support of the concept that beta-catenin/Tcf-4 is a
      transcriptional regulator for AKT1, results from our chromatin
      immunoprecipitation studies and luciferase assay showed that beta-catenin/Tcf-4
      binds to the potential binding sites in the gene promoter of AKT1. Furthermore,
      using immunohistochemistry, we found that Tcf-4 protein expression increased
      significantly in high-grade glioma in comparison to low-grade glioma and
      correlated with AKT1 expression. In conclusion, our results support the concept
      that beta-catenin/Tcf-4 directly regulates AKT1 in glioma, and these two proteins
      may cooperate with each other in exerting their oncogenic effects in glioma.

PMID- 21720710
TI  - Role of the long form leptin receptor and of the STAT3 signaling pathway in
      colorectal cancer progression.
AB  - Although a number of recent studies have reported the involvement of leptin in
      colorectal carcinogenesis, findings are contradictory and difficult to interpret.
      Our group has previously reported that leptin signaling might have an important
      role in the development of colorectal adenomas. In this study, we investigated
      leptin signaling in colorectal carcino-genesis focusing in particular on the
      differences in leptin signaling between colorectal adenoma and cancer. Whereas no
      significant differences in the serum leptin levels were observed among normal
      control subjects and adenoma/cancer patients, increased expression and activation
      of the long form leptin receptor (ObRL) was observed in colorectal adenoma and
      cancer tissues compared with the normal colorectal tissues. However, no
      significant differences were observed between the colorectal adenoma and cancer
      tissues. Significant increases in the phosphorylation levels of important
      molecules of the JAK/STAT signaling pathway, located downstream of leptin
      signaling, and transcriptional regulation of STAT3-downstream target molecules
      were observed in colorectal adenoma tissue compared with the findings in normal
      colorectal tissues. Furthermore, these changes were significantly more pronounced
      in colorectal cancer compared to colorectal adenoma tissues. This is the first
      analysis of leptin and JAK/STAT signaling in a human colorectal adenoma-carcinoma
      sequence. These results suggest that the STAT3-mediated leptin signaling through
      the activation of ObRL may be involved in colorectal carcinogenesis, both in
      adenoma formation and in the progression to cancer. STAT3 signaling in colorectal
      cancer may be mediated not only by leptin but by other factors.

PMID- 21720711
TI  - Cigarette smoke condensate-induced oxidative DNA damage and its removal in human
      cervical cancer cells.
AB  - Exposure to cigarette smoke is well documented to increase oxidative stress and
      could account for higher risk of cervical cancer in smokers. Cervical pre
      cancerous lesions that are initiated by human papillomavirus (HPV) infection
      generally regress in the absence of known risk factors such as smoking. 8
      oxodeoxyguanosine (8-oxodG) is a highly mutagenic oxidative DNA lesion that is
      formed by the oxidation of deoxyguanosine. In the present study, we examined: a)
      the effect of cigarette smoke condensate (CSC) on 8-oxodG formation in and its
      removal from HPV-transfected (ECT1/E6 E7), HPV-positive (CaSki) and HPV-negative
      (C33A) human cervical cancer cells, and b) the cell cycle progression and
      apoptosis in CSC-treated ECT1/E6 E7 cells. CSC induced 8-oxodG in a dose-
      (p=0.03) and time (p=0.002)-dependent fashion in ECT1/E6 E7 cells as determined
      by flow cytometry. A 2.4-fold higher level of 8-oxodG was observed in HPV
      positive compared with HPV-negative cells. However, 8-oxodG lesions were almost
      completely removed 72 h post-exposure in all cell lines as determined by
      ImageStream analysis. This observation correlates with the 2- and 5-fold increase
      in the p53 levels in ECT1/E6 E7 and CaSki cells with no significant change in
      C33A cells. We conclude that: a) cigarette smoke constituents induce oxidative
      stress with higher burden in HPV-positive cervical cancer cells and b) the
      significant increase observed in p53 levels in wild-type cervical cells (ECT1/E6
      E7 and CaSki) may be attributed to the p53-dependent DNA repair pathway while a
      p53-independent pathway in C33A cells cannot be ruled out.

PMID- 21720712
TI  - The DDAH/NOS pathway in human prostatic cancer cell lines: antiangiogenic effect
      of L-NAME.
AB  - Benign prostate hypertrophy (BPH) and prostate cancer (PC) are prostate chronic
      diseases that require a long period for development from a small lesion to
      clinical manifestation. PC is the most common cancer in men in Europe and the
      Americas. Tumor growth and metastasis depend upon the development of
      neovasculature around the tumor. This process, called angiogenesis, may be
      regulated by NO, and thus modulation of NO production could play an important
      role in tumor progression. Recent studies report the involvement of DDAH, an
      enzyme which metabolizes the endogenous NOS inhibitor ADMA, in the development of
      tumor vasculature. The aim of the present study was to verify the involvement of
      the DDAH/NOS pathway in the progression of prostate cancer. The effect of the NOS
      inhibitor L-NAME was evaluated in the human prostate cancer cell line LnCap and
      in BPH-1 cells which represent benign prostatic hypertrophy. Higher DDAH-2, eNOS,
      iNOS and VEGF expression was found in LnCap cells compared to BPH-1 cells. L-NAME
      treatment of LnCap cells resulted in a reduction in VEGF, iNOS and eNOS
      expression. VEGF, iNOS and eNOS inhibition is a promising approach for targeting
      tumor vasculature and certain NOS inhibitors could potentially serve as
      experimental agents for treatment of certain chemoresistant tumors, including
      prostate tumors. Moreover, since in our experimental conditions L-NAME was unable
      to reduce DDAH activity and expression, it is plausible to hypothesize the
      development of a targeted polypharmacological approach by developing dual and
      specific inhibitors of DDAH and NOS to better control NO biosynthesis.

PMID- 21720713
TI  - Changes in 5-HT1A receptor in the dorsal raphe nucleus in a rat model of post
      traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is characterized mainly by symptoms of re
      experiencing, avoidance and hyperarousal as a consequence of catastrophic and
      traumatic events that are distinguished from ordinary stressful life events.
      Single-prolonged stress (SPS) is an established animal model for post-traumatic
      stress disorder (PTSD). The dorsal raphe nucleus (DR)-serotonin (5-HT) system is
      markedly affected by swim stress and has been implicated in affective disorders.
      The 5-HT1A receptor (5-HT1AR) is critically involved in regulating mood and
      anxiety levels. In this study, we investigated changes in the expression of 5
      HT1AR in the DR of rats after SPS that may reveal part of the pathogenesis of
      PTSD. 5-HT1AR expression in the DR was examined using immunohistochemistry,
      Western blotting and reverse transcription polymerase chain reaction. The
      expression of 5-HT1AR in the DR after SPS exposure was increased when compared to
      that in the control group (P<0.05). These findings indicate an increase in 5
      HT1AR in the DR of SPS rats, which may play important roles in the pathogenesis
      of PTSD rats.

PMID- 21720714
TI  - Expression of erythroblastic leukemia viral oncogene homolog (erbBS) mRNAs and
      possible splice variants in 3T3-L1 preadipocytes.
AB  - Previously, we studied the erythroblastic leukemia viral oncogene homolog (erbB)
      family of tyrosine kinase growth factor receptors in terms of protein expression,
      modulation and activation in the 3T3-L1 cell line. In the present study, the
      presence of full-length erbB mRNAs, and splice or proteolytic erbB variants, was
      evaluated using RT-PCR. Epidermal growth factor receptor (EGFR)/erbB1 expression
      was confirmed. Wild-type (wt) ErbB2, human erbB2 (HER2)-extracellular domain
      (ECD) and herstatin mRNA expression were analyzed. Restriction analysis confirmed
      wt expression. 3T3-L1 cells exhibited HER2-ECD and herstatin mRNA expression,
      although at extremely low levels (compared to the control cell lines). ErbB3 cDNA
      was amplified using mouse mammary tumors and rat acines as positive controls.
      ErbB4 was not positively identified in these cells. In conclusion, this study
      demonstrates that 3T3-L1 cells express EGFR/erbB1, erbB2 and erbB3, and possibly,
      certain erbB2 splice or proteolytic variants, which are worth pursuing.

PMID- 21720715
TI  - Improved quantification for non-transferrin-bound iron measurement using high
      performance liquid chromatography by reducing iron contamination.
AB  - Non-transferrin-bound iron (NTBI) refers to all forms of iron in the plasma that
      bind to ligands other than transferrin, and is considered to be a marker of iron
      toxicity. A variety of analytical approaches for measuring NTBI have been
      reported; however, a clinically relevant level of sensitivity has yet to be
      achieved. In addition, insufficient values of NTBI in some patients and healthy
      subjects have led to the assumption that there may be contamination of reagents
      with background iron. The present study re-evaluated the analytical procedures of
      the assay with regard to the potential points of iron contamination in each step.
      NTA and tris carbonatocobaltate (III) solutions were prepared with removal of
      iron contamination, and then quantification of NTBI was performed. As a result,
      the sensitivity of the high-performance liquid chromatography (HPLC)-based NTBI
      method was improved by the successful reduction of background iron contamination.
      Application of our modified method proved that NTBI was detected even in healthy
      volunteers, although the concentrations were extremely low; the average NTBI
      levels were 0.206+/-0.091 uM (males, n=20) and 0.212+/-0.095 uM (females, n=16).
      Thus, our modification of the NTBI assay may be clinically meaningful, and may
      contribute to the understanding of the clinical significance of relatively low,
      but elevated concentrations of NTBI in diseases other than typical iron overload.

PMID- 21720716
TI  - Differential expression of somatostatin receptor subtype-related genes and
      proteins in non-functioning and functioning adrenal cortex adenomas.
AB  - Adrenocortical adenomas display highly variable expressions of somatostatin
      receptor (SSTR) subtypes, whose expression is mandatory (although not always
      sufficient) to achieve the positive effects of somatostatin (SST) analog therapy.
      Immunohistochemistry (IHC) is the main method used to investigate receptor
      protein expression. The molecular biology method - polymerase chain reaction
      (PCR) - is also often used to investigate receptor expression. Nevertheless, the
      expression of receptor mRNA and the respective receptor protein is not always
      synchronized. The aim of this study was to investigate SSTR expression by IHC in
      adrenal adenomas, to compare the results to data obtained by real-time PCR and to
      determine whether hormonally functioning and non-functioning adenomas differ in
      this respect. Adrenocortical adenomas were removed surgically from 13 females and
      2 males. The tissues were obtained from 9 non-functioning and 6 functioning
      adenomas. The intensity of IHC reaction was scored semiquantitatively by two
      independent observers. Real-time PCR was performed using pairs of primers in a
      reaction amplified along a gradient of temperatures. Amplified DNA was measured
      by monitoring SYBR-Green fluorescence. In non-functioning tumors, compatibility
      between IHC and PCR results was observed for SSTR 1 and 2 in 62.5% of the
      samples. Fifty percent of patients demonstrated compatibility for SSTR 4 and 5
      and 37.5% for SSTR 3. In hormonally active adenomas, total compatibility of both
      methods was noted for SSTR 2 (100%). The compatibility obtained for SSTR 5 was
      66.6%. We conclude that receptor gene and respective receptor protein expression
      are not always synchronized. Messenger RNA detection alone is not sufficient to
      predict the presence of the receptor protein acting as a target for SST and its
      analogs.

PMID- 21720717
TI  - Induction of G2/M arrest and apoptosis by sulforaphane in human osteosarcoma U2
      OS cells.
AB  - Sulforaphane is one of the most abundant isothiocyanates found in certain
      cruciferous vegetables, particularly broccoli. To date, sulforaphane has gained
      attention as a chemopreventive compound. The mechanism responsible for the
      anticancer effects of sulforaphane in osteosarcoma, however, is not clear. In
      this study, we demonstrate an anti-proliferative mechanism of sulforaphane in
      human osteosarcoma cells. The treatment of cells with sulforaphane resulted in a
      concentration- and time-dependent inhibition of growth and G2/M phase arrest of
      the cell cycle. This effect was associated with a decrease in protein expression
      of cyclin A and B1 and their activating partners, cyclin-dependent kinases (CDKs)
      1 and 2, with concomitant up-regulation of p21, a CDK inhibitor. Sulforaphane
      treatment also resulted in apoptosis as evidenced by an increase in annexin
      V+/propidium iodide- (V+/PI-) cells, the cleavage of 116-kDa poly (ADP-ribose)
      polymerase (PARP) and ICAD and oligonucleosomal DNA fragmentation. Taken
      together, these findings indicate that the molecular mechanisms underlying
      sulforaphane-mediated growth inhibition in U2-OS cells may be the modulation of
      the cell cycle machinery and the induction of apoptosis.

PMID- 21720718
TI  - A novel combined conjugate vaccine: enhanced immunogenicity of bFGF with CRM197
      as a carrier protein.
AB  - Tumor growth is partly dependent on tumor-associated angiogenesis, which is
      regulated by angiogenic growth factors. As the first angiogenic growth factor to
      be identified, basic fibroblast growth factor (bFGF) plays a major role in
      angiogensis and tumor growth and has been an effective target for anti-tumor
      therapy. However, due to its low immunogenicity, injection with bFGF alone cannot
      stimulate the body to produce a strong immune response. In this study, we
      investigated the role of CF (containing bFGF and CRM197) assisted by CpG and alum
      in enhancing antigen-specific immune response and suppressing the growth of
      murine colon carcinoma. The results revealed that compared to bFGF, CF could not
      stimulate NIH-3T3 fibroblast proliferation even at a concentration of 10 ug/ml in
      vitro. In vivo, the CF-CpG-alum produced a stronger antigen-specific immune
      response and inhibited tumor growth. The anti-tumor activity was associated with
      generating antigen-specific antibody, suppressing angiogenesis, promoting the
      apoptosis of tumor cells and inducing the mixed Th1 and Th2 responses. This
      indicates that CRM197 may be an innovative intramolecular adjuvant and provides a
      rational preservation for mouse CT26 colon carcinoma.

PMID- 21720719
TI  - Millimeter wave treatment inhibits the mitochondrion-dependent apoptosis pathway
      in chondrocytes.
AB  - Millimeter wave (MW) is an electromagnetic wave with a wavelength between 1 and
      10 mm and a frequency of 30-300 GHz that causes multiple biological effects, both
      locally and globally. MW has been widely used in clinical medicine. Although our
      previous work demonstrated that MW is capable of inhibiting sodium nitroprussiate
      (SNP)-induced apoptosis in chondrocytes, the precise mechanism of the anti
      apoptotic activity remains to be elucidated. The purpose of this study was to
      investigate the effects of MW in SNP-induced apoptotic chondrocytes. Sprague
      Dawley rat chondrocytes were isolated and cultured, and the cells were counted.
      Cell viability was evaluated using MTT assay. Cells were then treated with SNP
      and MW, and flow cytometry was used to detect apoptosis. Our results showed that
      MW treatment inhibited a SNP-induced mitochondrion-dependent pathway of
      apoptosis. MW treatment inhibited the loss of plasma membrane asymmetry
      (externalization of phosphatidylserine), collapse of mitochondrial membrane
      potential, and activation of caspase-9 and caspase-3. Taken together, the results
      indicate that MW inhibits the mitochondrion-dependent pathway of apoptosis in
      chondrocytes and this may, in part, explain its clinical effect in the treatment
      of osteoarthritis.

PMID- 21720720
TI  - Genetic polymorphisms associated with the development and clinical course of
      multiple sclerosis (review).
AB  - Multiple sclerosis (MS) is an autoimmune disease characterized by areas of
      inflammation, demyelination and axonal damage. The etiology of MS is
      multifactorial with an interaction between genetic, environmental and
      geographical factors. The objective of this study was to review the
      physiopathology and the genetic polymorphisms associated with the development and
      clinical course of MS. Studies carried out in populations worldwide showed that
      polymorphisms in the genes of the major histocompatibility complex (MHC) class II
      and class III have been associated with susceptibility, resistance and clinical
      forms of MS. Considerable attention has been focused on studies evaluating
      disease-modifying effects in MS that identified seven genes of probable
      importance such as the HLA class II, ApoE, IL-1ra, IL-1beta, TNF-alpha, TNF-beta
      and CCR5 genes. However, the results described in the literature about genetic
      biomarkers in MS are not consistent in the worldwide population. The detection of
      a single nucleotide polymorphism involved in the etiology and physiopathology of
      MS is very difficult and, it is likely that, several genetic polymorphisms are
      involved, each with a small contribution to the susceptibility or resistance to
      MS. Taken together the results show the need for continued research in
      genetically heterogeneous populations to identify new biomarkers associated with
      MS that could be used as prognostic markers or as therapeutic targets to modulate
      the autoimmune response in MS patients. This information may contribute to a
      better understanding of the physiopathology and treatment of MS, with the
      possibility of developing different therapeutic strategies according to the
      genetic profile of each individual.

PMID- 21720721
TI  - Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau).
AB  - A clinically and pathologically heterogeneous type of frontotemporal lobar
      degeneration has abnormal tau pathology in neurons and glia (FTLD-tau). Familial
      FTLD-tau is usually due to mutations in the tau gene (MAPT). Even FTLD-tau
      determined by MAPT mutations has clinical and pathologic heterogeneity.
      Tauopathies are subclassified according to the predominant species of tau that
      accumulates, with respect to alternative splicing of MAPT, with tau proteins
      containing three (3R) or four repeats (4R) of ~32 amino acids in the microtubule
      binding domain. In Pick's disease (PiD), 3R tau predominates, whereas 4R tau is
      characteristic of corticobasal degeneration (CBD) and progressive supranuclear
      palsy (PSP). Depending upon the specific mutation in MAPT, familial FTLD-tau can
      have 3R, 4R or a combination of 3R and 4R tau. PiD is the least common FTLD-tau
      characterized by neuronal Pick bodies in a stereotypic neuroanatomical
      distribution. PSP and CBD are more common than PiD and have extensive clinical
      and pathologic overlap, with no distinctive clinical syndrome or biomarker that
      permits their differentiation. Diagnosis rests upon postmortem examination of the
      brain and demonstration of globose tangles, oligodendroglial coiled bodies and
      tufted astrocytes in PSP or threads, pretangles and astrocytic plaques in CBD.
      The anatomical distribution of tau pathology determines the clinical presentation
      of PSP and CBD, as well as PiD. The basis for this selective cortical
      vulnerability in FTLD-tau is unknown.

PMID- 21720722
TI  - Target gene repression mediated by miRNAs miR-181c and miR-9 both of which are
      down-regulated by amyloid-beta.
AB  - MicroRNAs (miRNAs) are small non-coding RNA regulators of protein synthesis that
      are essential for normal brain development and function. Their profiles are
      significantly altered in neurodegenerative diseases such as Alzheimer's disease
      (AD) that is characterized by amyloid-beta (Abeta) and tau deposition in brain.
      How deregulated miRNAs contribute to AD is not understood, as their dysfunction
      could be both a cause and a consequence of disease. To address this question we
      had previously profiled miRNAs in models of AD. This identified miR-9 and -181c
      as being down-regulated by Abeta in hippocampal cultures. Interestingly, there
      was a remarkable overlap with those miRNAs that are deregulated in Abeta
      depositing APP23 transgenic mice and in human AD tissue. While the Abeta
      precursor protein APP itself is a target of miRNA regulation, the challenge
      resides in identifying further targets. Here, we expand the repertoire of miRNA
      target genes by identifying the 3' untranslated regions (3' UTRs) of TGFBI,
      TRIM2, SIRT1 and BTBD3 as being repressed by miR-9 and -181c, either alone or in
      combination. Taken together, our study identifies putative target genes of miRNAs
      miR-9 and 181c, which may function in brain homeostasis and disease pathogenesis.

PMID- 21720723
TI  - Cross-modal attention-switching is impaired in autism spectrum disorders.
AB  - This investigation aimed to determine if children with ASD are impaired in their
      ability to switch attention between different tasks, and whether performance is
      further impaired when required to switch across two separate modalities (visual
      and auditory). Eighteen children with ASD (9-13 years old) were compared with 18
      typically-developing children matched with the ASD group for mental age, and also
      with 18 subjects with learning difficulties matched with the ASD group for mental
      and chronological age. Individuals alternated between two different visual tasks,
      and between a different visual task and an auditory task. Children with ASD
      performed worse than both comparison groups at both switching tasks. Moreover,
      children with ASD had greater difficulty when different modalities were required
      than where only one modality was required in the switching task in comparison
      with participants matched in terms of mental and chronological age.

PMID- 21720724
TI  - The association between repetitive, self-injurious and aggressive behavior in
      children with severe intellectual disability.
AB  - We evaluated the independent association between adaptive behavior, communication
      and repetitive or ritualistic behaviors and self-injury, aggression and
      destructive behavior to identify potential early risk markers for challenging
      behaviors. Data were collected for 943 children (4-18 years, M = 10.88) with
      severe intellectual disabilities. Odds ratio analyses revealed that these
      characteristics generated risk indices ranging from 2 to 31 for the presence and
      severity of challenging behaviors. Logistic regressions revealed that high
      frequency repetitive or ritualistic behavior was associated with a 16 times
      greater risk of severe self-injury and a 12 times greater risk of showing two or
      more severe challenging behaviors. High frequency repetitive or ritualistic
      behaviors independently predict challenging behavior and have the potential to be
      early risk markers for self-injury and aggression of clinical significance.

PMID- 21720725
TI  - Symbolic play of preschoolers with severe communication impairments with autism
      and other developmental delays: more similarities than differences.
AB  - Children with autism are often described as having deficient play skills,
      particularly symbolic play. We compared the play of 35 children with autism to 38
      children with other developmental delays. All children were preschool-age and
      produced less than 20 different words. Results indicated no significant
      differences across the two groups in their play. Children with autism engaged in
      more conventional play, that is, putting objects together according to how the
      toys were constructed (e.g., pieces in a puzzle, lid on a teapot). Results also
      indicated high correlations between play, language, and cognitive measures.
      Findings indicate that play relates to language and cognitive levels yet may not
      discriminate children with autism and children with other developmental delays
      early in their development.

PMID- 21720726
TI  - Visual attention and autistic behavior in infants with fragile X syndrome.
AB  - Aberrant attention is a core feature of fragile X syndrome (FXS), however, little
      is known regarding the developmental trajectory and underlying physiological
      processes of attention deficits in FXS. Atypical visual attention is an early
      emerging and robust indictor of autism in idiopathic (non-FXS) autism. Using a
      biobehavioral approach with gaze direction and heart activity, we examined visual
      attention in infants with FXS at 9, 12, and 18 months of age with a cross
      sectional comparison to 12-month-old typically developing infants. Analyses
      revealed lower HR variability, shallower HR decelerations, and prolonged look
      durations in 12-month old infants with FXS compared to typical controls. Look
      duration and increased latency to disengage attention were correlated with
      severity of autistic behavior but not mental age.

PMID- 21720727
TI  - Factors affecting the accurate placement of percutaneous pedicle screws during
      minimally invasive transforaminal lumbar interbody fusion.
AB  - We retrospectively evaluated 488 percutaneous pedicle screws in 110 consecutive
      patients that had undergone minimally invasive transforaminal lumbar interbody
      fusion (MITLIF) to determine the incidence of pedicle screw misplacement and its
      relevant risk factors. Screw placements were classified based on postoperative
      computed tomographic findings as "correct", "cortical encroachment" or as "frank
      penetration". Age, gender, body mass index, bone mineral density, diagnosis,
      operation time, estimated blood loss (EBL), level of fusion, surgeon's position,
      spinal alignment, quality/quantity of multifidus muscle, and depth to screw entry
      point were considered to be demographic and anatomical variables capable of
      affecting pedicle screw placement. Pedicle dimensions, facet joint arthritis,
      screw location (ipsilateral or contralateral), screw length, screw diameter, and
      screw trajectory angle were regarded as screw-related variables. Logistic
      regression analysis was conducted to examine relations between these variables
      and the correctness of screw placement. The incidence of cortical encroachment
      was 12.5% (61 screws), and frank penetration was found for 54 (11.1%) screws. Two
      patients (0.4%) with medial penetration underwent revision for unbearable
      radicular pain and foot drop, respectively. The odds ratios of significant risk
      factors for pedicle screw misplacement were 3.373 (95% CI 1.095-10.391) for
      obesity, 1.141 (95% CI 1.024-1.271) for pedicle convergent angle, 1.013 (95% CI
      1.006-1.065) for EBL >400 cc, and 1.003 (95% CI 1.000-1.006) for cross-sectional
      area of multifidus muscle. Although percutaneous insertion of pedicle screws was
      performed safely during MITLIF, several risk factors should be considered to
      improve placement accuracy.

PMID- 21720728
TI  - Adjacent segment degeneration after single-segment PLIF: the risk factor for
      degeneration and its impact on clinical outcomes.
AB  - PURPOSE: To investigate: (1) the risk factors for radiologic cranial adjacent
      segment degeneration (ASD) after single-segment PLIF at the same level, and (2)
      the impact of the ASD on the clinical outcomes. METHODS: From October 2004 to May
      2009, 109 patients who underwent PLIF for degenerative instability at L4/5 and
      have more than 2 years follow-up were studied retrospectively. We measured the
      preoperative bone mineral density (BMD), lumbar lordosis, the lumbosacral joint
      angle, the lumbar inclination, the height and the dynamic angulation of the
      intervertebral space at the fused segments and the upper adjacent segment, the
      sliding displacement between L3 and L4. Clinical outcomes were evaluated using
      the Japanese Orthopedic Association (JOA) score and the Oswestry Disability Index
      (ODI). Patients were divided into two groups according to the progression of L3
      L4 degeneration: Group A without progression of L3-L4 degeneration, Group B with
      progression of L3-L4 degeneration. Clinical outcomes and radiologic measurement
      index between the two groups were compared, and the risk factors for progression
      of L3-L4 degeneration were analyzed. The correlation between clinical outcomes
      and progression of L3-L4 degeneration were also investigated. RESULTS: There were
      11 patients (22%) classified into Group A. No significant difference was found
      between the two groups in terms of the lordosis angle at L1 and S1, the laminar
      inclination at L3, the pre-existing L3-L4 disk degeneration, the lordosis angle
      of L4-L5, the lumbosacral joint angle and preoperative BMD (P > 0.05).
      Significant differences were found between the two groups in age. No significant
      difference was found between the two groups in the ODI and the JOA score at the
      final follow-up (P > 0.05). CONCLUSION: Radiologic degeneration of the cranial
      adjacent segment after single-segment PLIF did not significantly correlate with
      clinical outcomes. Age was a risk factor for radiologic degeneration, however,
      there was no significant correlation between degeneration and preoperative
      radiologic factors and bone mineral density (BMD).

PMID- 21720729
TI  - Health technology assessment (HTA) increasingly important in spine research.

PMID- 21720730
TI  - Protein kinase Calpha suppresses the expression of STC1 in MDA-MB-231 breast
      cancer cells.
AB  - Several protein kinase C (PKC) isoforms have been shown to influence different
      cellular processes that may contribute to the malignancy of breast cancer cells.
      To obtain insight into mechanisms mediating the PKC effects, global gene
      expression was analyzed in MDA-MB-231 breast cancer cells in which PKCalpha,
      PKCdelta or PKCepsilon had been down-regulated with siRNA. Gene set enrichment
      analyses revealed that hypoxia-induced genes were enriched among genes that
      increased in PKCalpha-down-regulated cells. The STC1 mRNA, encoding stanniocalcin
      1, was particularly up-regulated following depletion of PKCalpha and was also
      induced by hypoxia. Both hypoxia and PKCalpha down-regulation also led to
      increased STC1 protein levels. The results demonstrate that PKCalpha suppresses
      the expression of STC1 in breast cancer cells.

PMID- 21720731
TI  - Identification and sequence analysis of the Condylorrhiza vestigialis MNPV p74
      gene.
AB  - The baculovirus Condylorrhiza vestigialis multiple nucleopolyhedrovirus
      (CoveMNPV), isolated from C. vestigialis infected larvae in Parana (Brazil), was
      identified in our laboratory. A full-length clone was obtained from the CoveMNPV
      genome, of the gene that encodes the homolog to baculoviral p74, essential for
      oral infectivity which was then sequenced and characterized. The CoveMNPV p74
      gene (GenBank accession number EU919397) contains an ORF of 1935 bp that encodes
      a deduced protein of 73.61 kDa. The phylogenetic affiliations of the CoveMNPV
      gene were determined by a heuristic search of 40 aligned baculovirus p74
      nucleotide sequences using maximum parsimony (PAUP 4.0b4a). The phylogenetic
      analysis placed CoveMNPV within lepidopteran nucleopolyhedrovirus (NPV) Group I,
      Clade A, as being the closest to Choristoneura fumiferana defective NPV.

PMID- 21720732
TI  - An RNA-dependent RNA polymerase gene of a distinct Brazilian tospovirus.
AB  - The tospoviral RNA-dependent RNA polymerases (RdRp), or L proteins, perform
      several conserved functions during virus replication in host cells. In this
      study, an L segment sequence of 9,040 bp from a new tospovirus (family
      Bunyaviridae) naturally infecting bean (Phaseolus vulgaris L.) plants was
      characterized. It encodes the largest RdRp gene known yet for this genus, with
      deduced 2932aa and a molecular mass of approximately 336 kDa. A Lysine-rich C
      terminal extension was found, which apart from our isolate, was only recognized
      in another recently discovered tospovirus infecting Fabaceae, Soybean vein
      necrosis associated virus (SVNaV). Due to its distinct biological features and L
      protein-based phylogenetic analysis showing an almost equidistant position in
      comparison to Eurasian and American Tospovirus groups, as well as the clustering
      with SVNaV, we suggest the tentative name Bean necrotic mosaic virus for this
      unique isolate.

PMID- 21720733
TI  - Brain region white matter associations with visual selective attention.
AB  - To understand how normal variations in white matter relate to cognition,
      magnetization transfer imaging ratios (MTR) of a hypothesized neural network were
      associated with a test of visual selective attention (VST). Healthy adults (N =
      16) without abnormal signal on brain scans viewed a version of DeSchepper and
      Treisman's test of VST (1996) with two levels of processing (novel shape matching
      with and without distractors, contingency feedback). A hypothesized neural
      network and component regions was significantly associated with accuracy and
      response times when distractors were present, with betas predicting 55% of
      variance in accuracy, and 59% of response times. MTR for anterior and posterior
      cingulate, prefrontal region, and thalami comprised a model predicting 55% of
      accuracy when distractors were present, and the anterior cingulate accounted for
      the majority of this effect. Prefrontal MTR predicted longer response times which
      was associated with increased accuracy. Distal neural areas involved in complex,
      processing-driven tasks (error processing, response selection, and variable
      response competition and processing load) may be dependent on white matter fibers
      to connect distal brain regions/nuclei of a macronetwork, including prefrontal
      executive functions.

PMID- 21720734
TI  - Localizing sadness activation within the subgenual cingulate in individuals: a
      novel functional MRI paradigm for detecting individual differences in the neural
      circuitry underlying depression.
AB  - Variations in frontal lobe (FL) functional anatomy, especially the subgenual
      cingulate gyrus (SGC) suggest that mapping on an individual rather than group
      level may give greater insight regarding dysregulation of the neural circuitry
      involved in depression, as well as potentially provide more specific or
      individualized treatment plans for depressed patients. We designed a functional
      MRI task capable of imaging FL activity in individuals, including the SGC region,
      using a transient sadness paradigm. We sought to develop a method that may better
      detect individual differences of FL subregions related to sadness, since this
      region has been implicated to show dysregulation in depression. The task was
      based on a block design that also accommodates individual differences in
      responsivity to a sadness induction paradigm. Individual differences from nine
      non-depressed healthy volunteers were analyzed. We also performed functional
      connectivity analyses to further characterize our findings to the networks
      associated with the SGC in each individual. The study was designed to account for
      individual variation rather than using a true experimental design; therefore, no
      control group was necessary. As expected, due to inter-individual variability,
      the specific site of SGC activation during sadness varied across individuals.
      Activation was also observed in other brain regions consistent with other studies
      of induced sadness and depression. Patterns of functional connectivity to the SGC
      also highlighted neural circuits known to subserve sadness and depression. This
      task promises to more precisely localize a given individual's functional
      organization of the brain circuitry underlying sadness, and potentially
      depression, in an efficient, standardized way. This task could potentially aid in
      providing individualized targets in the treatment of depression.

PMID- 21720735
TI  - Determination of the geographical origin of Brazilian wines by isotope and
      mineral analysis.
AB  - In the present research, we studied wines from three different south Brazilian
      winemaking regions with the purpose of differentiating them by geographical
      origin of the grapes. Brazil's wide territory and climate diversity allow grape
      cultivation and winemaking in many regions of different and unique
      characteristics. The wine grape cultivation for winemaking concentrates in the
      South Region, mainly in the Serra Gaucha, the mountain area of the state of Rio
      Grande do Sul, which is responsible for 90% of the domestic wine production.
      However, in recent years, two new production regions have developed: the
      Campanha, the plains to the south and the Serra do Sudeste, the hills to the
      southeast of the state. Analysis of isotopic ratios of (18)O/(16)O of wine water,
      (13)C/(12)C of ethanol, and of minerals were used to characterize wines from
      different regions. The isotope analysis of delta(18)O of wine water and minerals
      Mg and Rb were the most efficient to differentiate the regions. By using isotope
      and mineral analysis, and discrimination analysis, it was possible to classify
      the wines from south Brazil.

PMID- 21720736
TI  - Synthesis of molecularly imprinted polymers via ring-opening metathesis
      polymerization for solid-phase extraction of bisphenol A.
AB  - The use of molecularly imprinted polymers (MIPs) prepared by ring-opening
      metathesis polymerization (ROMP) for bisphenol A (BPA) was reported in this
      article. The resulting MIPs have high imprinting and adsorption capacities, and
      can be used for separation and determination of BPA in environmental water
      samples. The successful application of ROMP in the molecular imprinting field is
      described here. For the first time, two cross-linkers (dicyclopentadiene and 2,5
      norbornadiene) and two Grubbs catalysts (first and second generation) were
      investigated to compare their effects on the binding performance of MIPs. The
      ROMP technique is able to create the imprinted polymers within 1 h under mild
      conditions. Furthermore, it can provide MIPs with obvious imprinting effects
      towards the template, very fast template rebinding kinetics, high binding
      capacity and appreciable selectivity over structurally related compounds. The
      adsorption process for MIPs in this study can be completed within 45 min, which
      is much faster than that of bulk MIPs synthesized by traditional free-radical
      polymerization. The resulting imprinting polymer was evaluated for its use as a
      sorbent support in an off-line solid-phase extraction approach to recover BPA
      from diluted aqueous samples. The optimized extraction protocol resulted in a
      reliable MISPE method suitable for selective extraction and preconcentration of
      BPA from tap water, human urine and liquid milk samples. This article
      demonstrates the practical feasibility of the MIPs prepared via ROMP as solid
      phase extraction materials.

PMID- 21720737
TI  - Simultaneous measurement of endogenous cortisol, cortisone,
      dehydroepiandrosterone, and dehydroepiandrosterone sulfate in nails by use of
      UPLC-MS-MS.
AB  - Steroid hormone concentrations are mostly determined by using different body
      fluids as matrices and applying immunoassay techniques. However, usability of
      these approaches may be restricted for several reasons, including ethical
      barriers to invasive sampling. Therefore, we developed an ultra-performance LC-MS
      MS method for high-throughput determination of concentrations of cortisol,
      cortisone, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) in small
      quantities of human nails. The method was validated for linearity, limits of
      detection and quantification, recovery, intra and interassay precision, accuracy,
      and matrix effect. Samples from 10 adult women were analyzed to provide proof-of
      principle for the method's applicability. Calibration curves were linear (r(2) >
      0.999) in the ranges 10-5000 pg mg(-1) for cortisol, cortisone, and DHEAS, and 50
      5000 pg mg(-1) for DHEA. Limits of quantification were 10 pg mg(-1) for cortisol,
      cortisone, and DHEAS, and 50 pg mg(-1) for DHEA. The sensitivity and specificity
      of the method were good, and there was no interference with the analytes. Mean
      recovery of cortisol, cortisone, DHEA, and DHEAS was 90.5%, 94.1%, 84.9%, and
      95.9%, respectively, with good precision (coefficient of variation <14% for all
      analytes) and accuracy (relative error (%) -8.3% to 12.2% for all analytes). The
      median (pg mg(-1), range) hormone concentrations were 69.5 (36-158), 65 (32-133),
      212 (50-1077), and 246 (115-547) for cortisol, cortisone, DHEA, and DHEAS,
      respectively. This method enables measurement of cortisol, cortisone, DHEA, and
      DHEAS in small quantities of human nails, leading to the development of
      applications in endocrinology and beyond.

PMID- 21720738
TI  - Metastatic Primary Leiomyosarcoma of the Pancreas to the Liver: Report of a
      Surgically Treated Case.

PMID- 21720739
TI  - Intestinal Metastasis of a Primary Lung Carcinoma Presenting as Mechanical Small
      Bowel Obstruction.

PMID- 21720740
TI  - Down-regulation of P-cadherin with PF-03732010 inhibits cell migration and tumor
      growth in gastric cancer.
AB  - P-cadherin is frequently up-regulated in solid tumors such as gastric, colon,
      lung, pancreatic and breast cancers. Although P-cadherin promotes cadherin
      mediated cell adhesion, the gastric cancer-linked regulation of P-cadherin has
      not been extensively investigated. In this study, we found epigenetic regulation
      of P-cadherin in human gastric cancer cells that was induced by treatment with
      DNA demethylating drug and histone deacetylase inhibitor. Silencing P-cadherin by
      using siRNA induces apoptosis in gastric cells and blocks expression of Tie-2, an
      angiogenic receptor tyrosine kinase. In contrast, ectopically expressed P
      cadherin by generating P-cadherin stable cell line enhances Tie-2 expression and
      cell mobility. We also demonstrated that inhibition of P-cadherin by PF-03732010,
      a fully humanized anti-P-cadherin IgG1 monoclonal antibody, suppressed cell
      migration in vitro and tumor growth in BALB/c nude mice bearing SNU620 gastric
      cancer xenograft. The data reported here are the first to reveal that the
      inhibition of P-cadherin decreases tumor cell migration and blocks a
      tumorigenesis by down-regulation of Tie-2 in gastric cancer. This demonstrates
      the potential for P-cadherin to be used as a target for treatment of gastric
      cancer.

PMID- 21720741
TI  - Sequential therapy with sunitinib and sorafenib in metastatic hepatocellular
      carcinoma.

PMID- 21720742
TI  - New developments in the management of chronic obstructive pulmonary disease and
      the overlap syndrome.
AB  - OPINION STATEMENT: The "overlap syndrome" is the concurrence of chronic
      obstructive pulmonary disease (COPD) with obstructive sleep apnea (OSA). This
      condition is not particularly well defined, and there is a paucity of data about
      the effects of any specific treatment on its outcomes. Until now, optimum
      treatment of the overlap syndrome could probably be best described as optimum
      treatment of each of its components, and there was no specific reason to think
      that treating one part of the syndrome would ameliorate the other part. However,
      recent observational data have demonstrated improved survival and reduced
      exacerbations in patients with the overlap syndrome who are treated with
      continuous positive airway pressure (CPAP). Physicians caring for patients with
      COPD should screen for OSA and have a low threshold for initiating CPAP treatment
      in those COPD patients who are found to have OSA.

PMID- 21720743
TI  - Effects of tamibarotene for the treatment of adult T cell leukemia.

PMID- 21720744
TI  - Phenotypic and genetic characterization of adult T-cell acute lymphoblastic
      leukemia with del(9)(q34);SET-NUP214 rearrangement.
AB  - SET-NUP214 rearrangement is a recently recognized recurrent chromosomal
      translocation mostly observed in T-ALL. In order to characterize this rare
      entity, we performed phenotypic and genetic characterization of SET-NUP214
      rearrangement through an investigation of a series of 40 consecutive samples of
      adult T-ALL that was selected among 229 adult ALL cases during 4 years in a
      single institution. Four cases (10%) of SET-NUP214 translocation were identified
      in our study. In all cases, diagnosis of T-ALL was established according to the
      World Health Organization (WHO) classification, and clonal TCR rearrangements
      were found. The immunophenotypic markers were indicative of the precursor nature
      of T lymphoblasts, and they expressed one or both of the myeloid-associated
      antigens (CD13, CD33). Conventional cytogenetic analysis revealed complex
      chromosomal aberrations in all four SET-NUP214 rearranged cases and
      del(12)(p13)/ETV6 was frequently involved. Array-CGH demonstrated additional
      genomic imbalances in addition to deletion 9q34. The genomic breakpoint
      sequencing identified breakpoints at SET intron 7 and NUP214 intron 17, and
      random nucleotide addition was found in two cases at the site of rearrangement.
      Our independently derived data set from a single institution confirms previous
      findings of SET-NUP214 rearrangement, indicates the relatively high incidence of
      SET-NUP214 rearrangement in adult T-ALLs, and also demonstrates comprehensive
      clinical, phenotypic, and genetic characteristics of this entity. Also, our
      report on genomic breakpoints demonstrates the homogeneity in the localization of
      the genomic breakpoints at 9q34. Concurrent chromosomal aberrations identified in
      this study should provide further areas of interest in investigation of SET
      NUP214-mediated leukemogenesis.

PMID- 21720745
TI  - Transcriptomic rationale for the synergy observed with dasatinib + bortezomib +
      dexamethasone in multiple myeloma.
AB  - Despite the advantage observed with novel drugs such as bortezomib, thalidomide,
      or lenalidomide, multiple myeloma (MM) remains incurable and there is a clear
      need for new drugs or combinations based on the pathogenetic mechanism of MM. One
      of the proposed mechanisms in MM pathogenesis is the involvement of kinase
      molecules in the growth and survival of myelomatous cells. In this study, we have
      explored the optimal combination for dasatinib, a tyrosine kinase inhibitor, in
      MM cells. A clear synergistic effect was observed with the triple combination of
      dasatinib with bortezomib and dexamethasone which was evident even in the
      presence of bone marrow microenvironment. Experiments performed on freshly
      isolated patients' cells also demonstrated potentiation of response in the triple
      as compared with the agents alone or in double combinations. Gene expression
      profiling experiments provided some clues on the transcriptional rationale
      underlying this potentiation, as the triple combination led to significant
      deregulation of genes involved in cell death, cell growth, proliferation, DNA
      replication, repair and recombination, and cell-cell signaling. Some of these
      results were further confirmed by apoptosis and cell cycle experiments and also
      by Western blot and PCR. These data provide the rationale for the use of this
      novel combination in MM patients.

PMID- 21720746
TI  - Young adult cancer survivors' psychosocial well-being: a cross-sectional study
      assessing quality of life, unmet needs, and health behaviors.
AB  - PURPOSE: This study compared the unmet needs, quality of life, and health
      behaviors (smoking, alcohol, and physical activity) of young adult cancer
      survivors to their older counterparts and age-related peers. METHODS: We
      conducted a subset analysis of the Cancer Survival Study baseline data collected
      from participants surveyed at approximately 6-7 months post-diagnosis. All 58
      young adults aged 18-40 years at the time of first primary cancer diagnosis and
      participating in the study were included. Their responses to the self
      administered SCNS-SF34, EORTC QLQ-C30, and standard items assessing smoking,
      alcohol consumption, and physical activity were compared to a random sample (n =
      58) of gender and cancer-type matched older adults (64+ years) participating in
      the same study. Young adult survivors' health behaviors were also compared to
      previously published data for age-related peers from the Australian general
      population. RESULTS: Young adult cancer survivors reported significantly lower
      levels of social functioning; higher levels of financial difficulties, sexuality
      needs, health systems and information needs; and better physical functioning than
      their older counterparts. A significantly higher percentage of young cancer
      survivors were current smokers compared to older survivors (16.1% vs. 3.7%, p =
      0.03), but is lower than that reported by age-related peers (24.8%). Compared to
      young cancer survivors (27.3%), significantly fewer older cancer survivors (8.3%,
      p = 0.046) and more age-related peers (53.6%) engaged in sufficient levels of
      physical activity. CONCLUSIONS: The impact of cancer on young adults seems to be
      specific. Future research should verify the unique concerns of young adult cancer
      survivors in large and diverse samples.

PMID- 21720747
TI  - Impact of marital status and race on outcomes of patients enrolled in Radiation
      Therapy Oncology Group prostate cancer trials.
AB  - INTRODUCTION: Previous studies by our group and others have demonstrated the
      importance of sociodemographic factors in cancer-related outcomes. The
      identification of these factors has led to novel approaches to the care of the
      high-risk cancer patient, specifically in the adoption of clinical interventions
      that convey similar benefits as favorable sociodemographic characteristics. This
      study examined the importance of marital status and race as prognostic indicators
      in men with prostate cancer. METHODS: This report is a meta-analysis of 3,570
      patients with prostate cancer treated in three prospective RTOG clinical trials.
      The Kaplan-Meier method was used to estimate the survival rate and the cumulative
      incidence method was used to analyze biochemical failure rate. Hazard ratios were
      calculated for all covariates using either the Cox or Fine and Gray's
      proportional hazards model or logistic regression model with associated 95%
      confidence intervals and p values. RESULTS: Hazard ratio (HR) for overall
      survival (OS) for single status compared to married status was 1.36 (95% CI, 1.2
      to 1.53). OS HR for non-White compared to White patients was 1.05 (CI 0.92 to
      1.21). In contrast, the disease-free survival (DFS) HR and biochemical failure
      (BF) HR were both not significantly different neither between single and married
      patients nor between White patients and non-White patients. Median time to death
      for married men was 5.68 years and for single men was 4.73 years. Median time for
      DFS for married men was 7.25 years and for single men was 6.56 years. Median time
      for BF for married men was 7.81 years and for single men was 7.05 years.
      CONCLUSIONS: Race was not associated with statistically significant differences
      in this analysis. Congruent with our previous work in other cancer sites, marital
      status predicted improved prostate cancer outcomes including overall survival.
      IMPLICATIONS FOR CANCER SURVIVORS: Prostate cancer is the most common visceral
      cancer in men in the USA. The stratification of prostate cancer risk is currently
      modeled solely on pathologic prognostic factors including PSA and Gleason Score.
      Independent of these pathologic prognostic factors, our paper describes the
      central sociodemographic factor of being single as a negative prognostic
      indicator. Single men are at high risk of poorer outcomes after prostate cancer
      treatment. Intriguingly, in our group of patients, race was not a significant
      prognostic factor. The findings in this paper add to the body of work that
      describes important sociodemographic prognostic factors that are currently
      underappreciated in patients with cancer. Future steps will include the
      validation of these findings in prospective studies, and the incorporation of
      clinical strategies that identify and compensate for sociodemographic factors
      that predict for poorer cancer outcomes.

PMID- 21720748
TI  - Effect of advanced cancer patients' awareness of disease status on treatment
      decisional conflicts and satisfaction during palliative chemotherapy: a Korean
      prospective cohort study.
AB  - PURPOSE: Our purpose was to evaluate the effect of cancer patients' awareness of
      their incurable disease status on decisional conflict and satisfaction with
      treatment choice. METHODS: In this prospective cohort study, advanced cancer
      patients who were offered palliative chemotherapy completed questionnaires on
      their knowledge of their condition, their treatment decision conflicts, and their
      satisfaction with their treatment decisions. RESULTS: We enrolled 98 patients; 94
      reported that they were aware of their advanced status and 50 were not.
      Decisional conflicts for all patients showed a significant decrease after
      treatment, but aware patients were significantly more satisfied with their
      decision (P = 0.02). CONCLUSION: Patients' awareness of their incurable status
      was associated with greater satisfaction with their decision to receive
      palliative chemotherapy.

PMID- 21720749
TI  - Microbiological and host factors are involved in promoting the periodontal
      failure of metaloceramic crowns.
AB  - This study was aimed at looking into the microbiological/inflammatory parameters
      predicting the periodontal success/failure of fixed prostheses. Microbiological
      and inflammatory patterns were studied at 102 sites having metaloceramic crowns
      in place from 3 to 6 years and divided in healthy sites (HS), gingivitis affected
      (MG), and periodontitis affected (PB). Total bacterial flora and selected
      indicator species in subgingival plaque were quantified by quantitative real-time
      PCR. The concentrations of IL-1beta, IL-6, and TNF-alpha were determined in
      gingival crevicular fluid (GCF) by enzyme-linked immunosorbent assays. The
      experimental sites showed no significant difference with respect to the age and
      gender of the patients and to the position of the crown margins. Poor marginal
      adaptation was significantly higher in MG and PB. The total amounts of bacteria
      per probing depth showed no significant differences among the three groups and
      their controls, while both MG and PB sites showed altered patterns in the
      distribution of specific bacteria. Both MG and PB sites showed significantly
      higher levels of inflammatory cytokines in GCF. The control teeth of PB subjects
      showed significantly higher levels of IL-1beta as compared to other control
      sites. Data confirm that the application of metaloceramic crowns is a factor of
      risk for the development of gingival/periodontal inflammation. This risk is
      possibly associated with microbiological and host factors that predispose to the
      onset of periodontal alterations at sites reconstructed with metaloceramic
      crowns. These factors, once their role is confirmed by longitudinal studies,
      could be used to set up rapid tests to early predict the onset of periodontal
      disease at reconstructed sites.

PMID- 21720750
TI  - The eligibility of the free fibula graft for masticatory rehabilitation using
      monocortical implants insertion--a morphologic and biomechanical study.
AB  - The use of the vascularized fibula graft has already been established for
      reconstruction of the mandible following ablative surgery. In order to
      reconstruct the vertical height of the alveolar process and improve implant
      position as well as angulation, some therapeutic options are available, including
      primary use of the fibula as a double-barrel graft and vertical distraction as
      well as later augmentation with avascular bone grafts. We analyzed the anatomic
      and morphologic features in 40 fibula bones of 20 cadavers and provided the mean
      cortical thickness of different transplant sites. Furthermore, we investigated
      the primary implant stability of dental implants inserted monocortically in
      harvested fibula segments using established biomechanical methods as well as
      Periotest((r)). The minimal bone height of the clinically relevant segments of
      the fibula transplant measured 9.06 +/- 0.45 mm, which was assessed in the most
      distal part. In contrast, a maximal total bone height of 15.46 +/- 0.78 was
      observed in the middle segment of the fibula bone. We assessed sufficient primary
      stability in all inserted implants as well as a reliable relative micro-movement
      of the implants in the fibula bone. Fibula graft as a single-barrel graft alone
      may provide through monocortical implant insertion a further refinement of the
      method to fit complex requirements and shorten prolonged therapeutic procedures.
      Monocortical implant insertion in the fibula graft would simplify oral
      rehabilitation after ablative surgery of the jaw and reduce costs as well as
      therapy period.

PMID- 21720752
TI  - Cervicofacial pain associated with Eagle's syndrome misdiagnosed as trigeminal
      neuralgia.
AB  - BACKGROUND: Eagle's syndrome is characterized by the symptoms of recurrent throat
      pain, pharyngeal foreign body sensation, dysphagia, referred otalgia, and neck
      pain. The treatment for Eagle's syndrome can be pharmacologically, surgically, or
      both. The surgical management consists of two major procedures: the transoral
      approach or the extraoral-cervical approach. CASE REPORT: A 64-year-old patient
      with a severe cervical pain on the left side was evaluated with no defined
      diagnosis. During physical examination, an elongated styloid process could be
      palpated and with CT scan image, the Eagle's syndrome diagnosis was done. The
      patient was successfully submitted to surgical resection of the elongated styloid
      process on the left side by an extraoral-cervical approach. After 6 months follow
      up, the patient referred no symptom after the surgical treatment. CONCLUSION: The
      extraoral/cervical approach is a safe alternative that achieves adequate
      treatment of Eagle's syndrome.

PMID- 21720753
TI  - Roles of D1-like dopamine receptors in the nucleus accumbens and dorsolateral
      striatum in conditioned avoidance responses.
AB  - RATIONALE: Aversively motivated learning is more poorly understood than
      appetitively motivated learning in many aspects, including the role of dopamine
      receptors in different regions of the striatum. OBJECTIVES: The present study
      investigated the roles of the D1-like DA receptors in the nucleus accumbens (NAc)
      and dorsolateral striatum (DLS) on learning and performance of conditioned
      avoidance responses (CARs). METHODS: Adult male Wistar rats received
      intraperitoneal (i.p.), intra-NAc, or intra-DLS injections of the D1 dopamine
      receptor agonist SKF 81297 or the D1 receptor antagonist SCH 23390 20 min before
      or immediately after a training session in the CAR task two-way active avoidance,
      carried out 24 h before a test session. RESULTS: Pre-training administration of
      SCH 23390, but not SKF 81297, caused a significant decrease in the number of CARs
      in the test, but not in the training session, when injected into the DLS, or in
      either session when injected into the NAc. It also caused a significant increase
      in the number of escape failures in the training session when injected into the
      NAc. Systemic administration caused a combination of these effects. Post-training
      administrations of these drugs caused no significant effect. CONCLUSIONS: The
      results suggest that the D1-like receptors in the NAc and DLS play important,
      though different, roles in learning and performance of CAR.

PMID- 21720754
TI  - Effects of acute stress on acquisition of nicotine conditioned place preference
      in adolescent rats: a role for corticotropin-releasing factor 1 receptors.
AB  - RATIONALE: Studies indicate that adolescence is a time of increased sensitivity
      to the rewarding effects of nicotine, and that stress is associated with an
      increased risk for smoking initiation in this age group. It is possible that
      stress leads to increased nicotine use in adolescence by augmenting its rewarding
      properties. Corticotropin-releasing factor type 1 receptors (CRF-R1) mediate
      physiological and behavioral stress responses. They may also mediate stress
      induced potentiation of activity in multiple neural substrates implicated in
      nicotine reward. OBJECTIVES: The aim of the present study was to determine the
      effect of acute stressor exposure on single trial nicotine conditioned place
      preference (CPP) in adolescent male rats using a biased CPP procedure and the
      role of CRF-R1 in this effect. RESULTS: A single episode of intermittent
      footshock administered 24 h before the start of place conditioning dose
      dependently facilitated acquisition of CPP to nicotine (0.2, 0.4, and 0.6 mg/kg).
      Pretreatment with CP-154,526 (20 mg/kg), a selective CRF-R1 antagonist, 30 min
      before footshock exposure significantly attenuated the effect of prior stress to
      facilitate nicotine CPP acquisition. CP-154,526 pretreatment had no effect in
      animals conditioned with a nicotine dose that produced CPP under non-stress
      conditions, suggesting a specific role for CRF-R1 following stress. CONCLUSIONS:
      Taken together, the results suggest that during adolescence, nicotine reward is
      enhanced by recent stressor exposure in a manner that involves signaling at CRF
      R1. Information from studies such as this may be used to inform efforts to
      prevent and treat adolescent nicotine dependence.

PMID- 21720755
TI  - Effects of neurotensin gene knockout in mice on the behavioral effects of
      cocaine.
AB  - RATIONALE: The neuropeptide neurotensin (NT), which has been implicated in the
      modulation of dopamine signaling, is expressed in a subset of dopamine neurons
      and antagonism of the NT receptor has been reported to reduce psychostimulant
      induced behavior. Gene knockout (KO) of the neurotensin/neuromedin N precursor
      provides an approach to delineating possible roles of endogenous NT in
      psychostimulant-induced responses. OBJECTIVES: Involvement of NT in cocaine
      responses was examined by comparing acute and conditioned locomotor responses,
      conditioned place preference, and sensitization in wild-type (WT), heterozygous,
      and homozygous NT KO mice. RESULTS: NT KO mice did not differ from their WT or
      heterozygous littermates in either baseline or acute cocaine-stimulated locomotor
      activity. The locomotor stimulant effects of cocaine were slightly prolonged in
      these mice under some, but not all, experimental conditions. The rewarding
      effects of cocaine as assessed in the conditioned place preference and
      conditioned locomotion paradigms were also similar between genotypes at all
      cocaine doses tested. CONCLUSIONS: These results suggest that endogenous NT is
      not involved in cocaine-mediated behaviors in most circumstances, but under some
      conditions, a slight prolongation of the effects of cocaine was observed in the
      absence of endogenous NT.

PMID- 21720756
TI  - Reciprocal interactions of Fgf10/Fgfr2b modulate the mouse tongue epithelial
      differentiation.
AB  - The molecular mechanisms for epithelial differentiation have been studied by
      observing skin development in embryogenesis, but the early signaling modulations
      involved in tongue epithelial differentiation are not completely understood.
      Based on the gene expression patterns of the Fgf signaling molecules and previous
      results from Fgf10 and Fgfr2b knockout mice, it was hypothesized that there would
      be fundamental signaling interactions through the epithelial Fgfr2b and its
      mesenchymal ligand Fgf10 to regulate tongue epithelium differentiation. To
      elucidate these reciprocal interactions in tongue epithelial differentiation,
      this study employed an in vitro tongue organ culture system with antisense
      oligodeoxynucleotides (AS-ODNs) and recombinant protein-soaked bead implantation
      for the loss-of-function and gain-of-function studies. Functional analysis of Fgf
      signaling revealed precise reciprocal interactions, which showed that mesenchymal
      Fgf10 rather than Fgf7 modulates tongue epithelial differentiation via Fgfr2b in
      a temporal- and spatial-specific manner.

PMID- 21720757
TI  - C-reactive protein (CRP) gene polymorphisms: implication in CRP plasma levels and
      susceptibility to acute myocardial infarction.
AB  - C-reactive protein (CRP) is one of the many molecular factors involved in
      pathogenesis of coronary artery disease which its plasma levels are associated
      with increased risk of cardiovascular events. The present study designed to
      determine whether polymorphisms in the CRP gene are associated with plasma CRP
      levels and susceptibility to acute myocardial infarction (AMI). Plasma CRP levels
      were measured in patients with AMI and control subjects and genomic DNA and
      peripheral blood mononuclear cells (PBMCs) were extracted. The -717A/G and
      1059G/C CRP polymorphisms were detected. The mRNA expression of CRP gene and
      plasma levels of CRP and interleukin-6 (IL-6) were also analyzed. The -717A/G
      variation was significantly associated with higher CRP levels, but 1059G/C
      variation was associated with lower CRP levels. The AA genotype frequency of 
      717A/G variation was significantly more frequent in the patients than control
      subjects. By contrast, the genotype and allele distribution in 1059G/C of patient
      were not statistically different between patients and controls. There were
      significant differences in circulating levels of CRP and IL-6 in the patients
      than in controls. The mRNA expression levels of CRP were significantly higher in
      the patient plasma compared with controls. Our results indicate relationship
      between many polymorphisms in CRP gene and risk of AMI which suggest that genetic
      variations in CRP might be helpful for determining susceptibility to AMI in
      Iranian patients. In addition, CRP gene polymorphisms are associated with plasma
      CRP levels and susceptibility to AMI might be related to CRP gene expression
      which affects its plasma levels.

PMID- 21720758
TI  - Identification and expression analysis of chitinase genes related to biotic
      stress resistance in Brassica.
AB  - Brassica is a very important vegetable group because of its contribution to human
      nutrition and consequent economic benefits. However, biotic stress is a major
      concern for these crops and molecular biology techniques offer the most efficient
      of approaches to address this concern. Chitinase is an important biotic stress
      resistance-related gene. We identified three genes designated as Brassica
      chitinase like protein (BrCLP1), BrCLP2 and BrCLP3 from a full-length cDNA
      library of Brassica rapa cv. Osome. Sequence analysis of these genes confirmed
      that BrCLP1 was a class IV chitinase, and BrCLP2 and BrCLP3 were class VII
      chitinases. Also, these genes showed a high degree of homology with other biotic
      stress resistance-related plant chitinases. In expression analysis, organ
      specific expression of all three genes was high except BrCLP1 in all the organs
      tested and BrCLP2 showed the highest expression compared to the other genes in
      flower buds. All these genes also showed expression during all developmental
      growth stages of Chinese cabbage. In addition, BrCLP1 was up-regulated with
      certain time of infection by Pectobacterium carotovorum subsp. carotovorum in
      Chinese cabbage plants during microarray expression analysis. On the other hand,
      expression of BrCLP2 and BrCLP3 were increased after 6 h post inoculation (hpi)
      but decreased from 12 hpi. All these data suggest that these three chitinase
      genes may be involved in plant resistance against biotic stresses.

PMID- 21720759
TI  - Molecular characterization and expression analysis of osteopontin cDNA from
      lactating mammary gland in yak (Bos grunniens).
AB  - Osteopontin (OPN) is a secreted phosphorylated glycoprotein. It has an important
      role in mammary gland development and lactation, as well as, is thought to be a
      potential candidate gene for lactation traits. In the present work, we isolated
      and characterized a full-length open reading frame (ORF) of yak OPN cDNA from
      lactating mammary tissue, and examined its expression pattern in mammary gland
      during different stages of lactation, as well as, the recombinant OPN protein of
      yak was expressed successfully in E. coli. The sequencing results indicated that
      the isolated cDNA was 1132-bp in length containing a complete ORF of 837-bp. It
      encoded a precursor protein of yak OPN consisting of 278 amino acid with a signal
      peptide of 16 amino acids. Yak OPN has a predicted molecular mass of 29285.975 Da
      and an isoelectric point of 4.245. It had an identity of 65.50-99.16% in cDNA,
      identity of 52.06-98.56% and similarity of 65.40-98.56% in deduced amino acids
      with the corresponding sequences of cattle, buffalo, sheep, goat, pig, human, and
      rabbit. The phylogenetic analysis indicated that yak OPN had the closest
      evolutionary relationship with that of cattle, and next buffalo. In mammary
      gland, yak OPN was generally transcribed in a declining pattern from colostrum
      period to dry period with an apparent increase of OPN expression being present in
      the late period of lactation compared with peak period of lactation. Western blot
      analysis indicated that His-tagged yak OPN protein expressed in E. coli could be
      recognized not only by an anti-His-tag antibody but also by an anti-human OPN
      antibody. These results from the present work provided a foundation for further
      insight into the role of OPN gene in yak lactation.

PMID- 21720760
TI  - Identification and characterization of a LEA family gene CarLEA4 from chickpea
      (Cicer arietinum L.).
AB  - Late-embryogenesis abundant (LEA) proteins have been reported to be closely
      correlated with the acquisition of desiccation tolerance during seed development
      and response of plant to drought, salinity, and freezing, etc. In this study, a
      LEA gene, CarLEA4 (GenBank accession no. GU247511), was isolated from chickpea
      based on a cDNA library constructed with chickpea seedling leaves treated by
      polyethylene glycol (PEG). CarLEA4 contained two exons and one intron within
      genomic DNA sequence and encoded a putative polypeptide of 152 amino acids.
      CarLEA4 had a conserved pfam domain, and showed high similarity to the group 4
      LEA proteins in secondary structure. It was localized in the nucleus. The
      transcripts of CarLEA4 were detected in many chickpea organs including seedling
      leaves, stems, roots, flowers, young pods, and young seeds. CarLEA4 was inhibited
      by leaf age and showed expression changes in expression during seed development,
      pod development and germination. Furthermore, the expression of CarLEA4 was
      strongly induced by drought, salt, heat, cold, ABA, IAA, GA(3) and MeJA. Our
      results suggest that CarLEA4 encodes a protein of LEA group 4 and may be involved
      in various plant developmental processes and abiotic stress responses.

PMID- 21720761
TI  - PI3 Kinase regulation of neural regeneration and muscle hypertrophy after spinal
      cord injury.
AB  - Spinal cord injury (SCI) is a serious neurotrauma that can lead to life-long
      disability; to date, no suitable therapeutic strategy exists. Axons do not
      regenerate after SCI in adult mammals and loss of skeletal muscle mass occurs
      very rapidly after SCI. Promotion of neurite growth through improving the
      extracellular environment allows only a limited degree of axon regeneration. The
      phosphatidylinositol-3 kinase (PI3K)/Akt pathway and its downstream targets
      ("mammalian target of rapamycin," mTOR, and glycogen synthase kinase-3), which
      regulate cell growth and proliferation in many tissues, have been suggested to
      play an important role in regulation of the intrinsic axonal regeneration and
      muscle hypertrophy. This review is focused on recent progress in our
      understanding of the PI3K pathway in the modulation of axonal regeneration and
      muscle hypertrophy after SCI.

PMID- 21720762
TI  - Two different docetaxel resistant MCF-7 sublines exhibited different gene
      expression pattern.
AB  - The objective of the present study was to investigate gene expression pattern of
      two docetaxel resistant MCF-7 breast carcinoma sublines step wisely selected in
      30 and 120 nM docetaxel. Cell proliferation assay was performed in order to
      demonstrate development of docetaxel resistance. cDNA microarray analysis was
      performed using Affymetrix((r)) Human Genome U133 Plus 2.0 Arrays in duplicate
      experiments. Quantitative and semi-quantitative gene expression analysis was also
      performed to confirm gene expression analysis for selected genes. XTT results
      demonstrated that 30 (MCF-7/30nM DOC) and 120 nM (MCF-7/120nM DOC) docetaxel
      selected cells were 13- and 47-fold resistant, respectively. cDNA microarray
      analysis demonstrated that expression profiles of MCF-7 and MCF-7/30nM DOC were
      more similar to each other where expression profile of MCF-7/120nM DOC was
      different as examined by line graphs and scatter plots. 2,837 and 4,036 genes
      were significantly altered in 30 and 120 nM docetaxel resistant sublines,
      respectively. Among these, 849 genes were altered in common in two docetaxel
      resistant sublines. Antiapoptotic gene expression (e.g., Bcl-2 and APRIL) were
      noticeably altered in MCF-7/30nM DOC. However, docetaxel resistance in MCF
      7/120nM DOC were more complicated with the involvement of ECM related gene
      expression, cytokine and growth factor signaling, ROS metabolism and EMT related
      gene expression together with higher level of MDR1 expression. Expression
      profiles in 30 and 120 nM docetaxel resistant sublines changed gradually with
      increasing resistance index. Drug resistance development seems to be step wise
      event in MCF-7 cells.

PMID- 21720763
TI  - Infliximab therapy efficacy and persistence at a Canadian academic centre despite
      a change in access procedure.
AB  - Patients treated with infliximab at our centre through a special access programme
      (initiation group) had long-standing, treatment-resistant rheumatoid arthritis.
      The clinical experience for these patients may be different than that of patients
      initiating treatment after provincial government approval and cost coverage for
      all anti-tumour necrosis factor (anti-TNF) therapies became effective
      (contemporary group). We compared adverse events, drug survival and reasons for
      discontinuation in these two groups. A prospective cohort of patients treated
      with an anti-TNF therapy was assembled following the availability of infliximab
      in 2000. By protocol, patients are assessed for treatment response,
      discontinuation or switching of biologic agents and occurrence of adverse events.
      We report on 231 patients treated with infliximab therapy (680 patient-years).
      Both groups had similar drug survival (median 2.2 years) and rates of serious
      adverse events including infusion reactions (6.8 per 100 patient-years) and
      serious infections (3.4 per 100 patient-years). More patients in the initiation
      group discontinued infliximab for adverse events [39/139 (28%) vs. 15/92 (16%), p
      = 0.04] and developed drug-induced lupus [8/139 (6%) vs. 0%, p = 0.02].
      Subsequent biologics were discontinued for the same reason as infliximab in only
      12% (15/123) of cases. Patients treated with infliximab through a special access
      programme have comparable drug survival compared to a contemporary group, despite
      experiencing more adverse events. Only a minority of patients discontinuing
      infliximab due to the lack of effect or adverse events experience the same fate
      with subsequent anti-TNF agents.

PMID- 21720764
TI  - Rhos and Rho kinases in the rat prostate: their possible functional roles and
      distributions.
AB  - As there is increasing evidence that Rho-Rho kinase (ROCK) pathway plays an
      important role in the proliferation and contraction in many tissues, we
      investigated the contractile role of a ROCK inhibitor, fasudil, and the
      distribution of RhoA, RhoB, RhoC, ROCK1, and ROCK2 in the rat prostate. Twelve
      week-old Sprague-Dawley rat prostate was used in this study. Rat prostatic
      contractile responses induced by carbachol and norepinephrine were investigated
      in organ bath studies without or with 10(-7), 10(-6), and 10(-5) M of a non
      selective ROCK inhibitor, fasudil. Immunoblot analysis and immunohistochemical
      staining were performed to investigate the participation levels of RhoA, RhoB,
      RhoC, ROCK1, and ROCK2. The E(max) values induced by carbachol and norepinephrine
      were similar in the rat prostate. Fasudil significantly inhibited carbachol- or
      norepinephrine-induced prostatic contractions in a dose-dependent manner. Fasudil
      10(-5) M reduced the initial prostatic contraction (without fasudil) to 56.7 +/-
      5.9% for carbachol and to 45.7 +/- 12.3% for norepinephrine. Amounts of RhoA,
      RhoB, RhoC, ROCK1, and ROCK2 were detected by immunoblot analysis in the
      prostate. Immunohistochemical study revealed that RhoA, RhoB, RhoC, ROCK1, and
      ROCK2 were all positive in the prostatic smooth muscle, while there were some
      differences of distributions of Immunoreactivities between these enzymes in the
      prostatic glandula. Our data indicated that rat prostate contains RhoA, RhoB,
      RhoC, ROCK1, and ROCK2, which play an important role in the autonomic nerve
      mediated contractile responses in the prostate.

PMID- 21720765
TI  - Spatiotemporal profile of N-cadherin expression in the mossy fiber sprouting and
      synaptic plasticity following seizures.
AB  - Recurrent seizures can induce mossy fiber sprouting (MFS), of the hippocampal
      dentate gyrus, and synaptic reorganization in mature brain. This changes local
      circuits and provides a structural basis for epileptogenesis in the hippocampus.
      However, the mechanisms of MFS and synaptic reorganization still remain unclear.
      Neural-cadherin (N-cadherin), a calcium adhesion molecule, plays an important
      role in neurite outgrowth, pathfinding, and synaptic specificity of early central
      nervous system development. It is unknown whether N-cadherin is involved in MFS
      after seizures in mature brain. To further examine the correlation between MFS
      and N-cadherin expression, we separately labeled MFS and N-cadherin with Timm
      staining and antibody in adult rats after status epilepticus (SE). Timm staining
      revealed that MFS is observed in the inner molecular layer of dentate gyrus of
      rats 2 and 4 weeks after SE. The observed MFS migrated from the hilus to the
      granule cell layer, gradually extending axons into the inner molecular layer to
      form an intense band. Immunohistochemical staining of N-cadherin revealed that
      the upregulated expression of N-cadherin was concentrated in the position of
      mossy fiber axonal sprouts of rats 1-4 weeks after SE, and that it was earlier
      than MFS. The spatial and temporal distribution consistence of N-cadherin and
      Timm staining supported the correlation that exists between N-cadherin expression
      and the process of aberrant MFS. This result suggests that N-cadherin may be
      involved in the pathfinding and synaptic specificity of MFS in mature brain after
      seizures, and can play an important role in the targeted growth of mossy fibers.

PMID- 21720766
TI  - Elevated expression of activated Na(+)/H(+) exchanger protein induces hypertrophy
      in isolated rat neonatal ventricular cardiomyocytes.
AB  - The plasma membrane protein the Na(+)/H(+) exchanger isoform1 (NHE1) has been
      implicated in various cardiac pathologies including ischemia/reperfusion damage
      to the myocardium and cardiac hypertrophy. Levels of NHE1 protein and activity
      are elevated in cardiac disease; however, the mechanism by which these factors
      contribute to the accompanying hypertrophy in the myocardium is still not clear.
      To investigate the mechanism of NHE1-induced hypertrophy in the myocardium we
      constructed two adenoviral vectors expressing either wild type NHE1 protein or a
      constitutively active NHE1 protein. Infection of neonatal rat ventricular
      cardiomyocytes (NRVM) resulted in elevated expression of both wild type NHE1 or
      constitutively active NHE1. Only expression of activated NHE1 protein resulted in
      an increase in cell size and in an increase in protein synthesis in isolated
      cardiomyocyte cells. The results demonstrate that expression of activated NHE1
      promotes cardiac hypertrophy in isolated cardiac cells and that simple elevation
      of levels of wild type NHE1 protein does not have a significant hypertrophic
      effect in NRVM. The results suggest that regulation of NHE1 activity is a
      critical direct effector of the hypertrophic effect induced in the myocardium by
      the NHE1 protein.

PMID- 21720767
TI  - Effect of central myelin on the proliferation and differentiation into O4(+)
      oligodendrocytes of GFP-NSCs.
AB  - Myelin is a biologically active mutilamellar that is formed by oligodendrocytes
      (OLs) in the central nervous system (CNS) and ensheathes axons (Ishii et al.,
      Proc Natl Acad Sci USA 106:14605-14610, 2009). Myelin damage is related to
      neurological trauma such as spinal cord injury (SCI). In this article, we
      investigated whether myelin derived from rat spinal cord can influence the
      proliferation of neural stem cells (NSCs) and NSCs differentiation into
      oligodendrocytes in vitro. After extracting myelin, we verified that myelin
      preparation was successful by western blot analysis. Then, we explored the
      effects of different myelin concentrations on the NSCs proliferation by MTT
      assays. Our results showed that 2 MUg/ml myelin can promote the proliferation of
      NSCs, while NgR antibody can antagonize the effect. In addition, myelin can
      inhibit the differentiation of NSCs into O4(+) oligodendrocytes impeding them
      maturation. In conclusion, these results suggested that central myelin can affect
      the proliferation and differentiation of NSCs, thus promoting us to understand
      further the complex roles of myelin in NSCs after CNS injury.

PMID- 21720768
TI  - Expression of beta1,3-N-acetylglucosaminyltransferases during differentiation of
      human acute myeloid leukemia cells.
AB  - The expressions of beta1,3-N-acetylglucosamonyltransferase-2 and -8 (beta3GnT-2,
      beta3GnT-8),-the two main glycosyltransferases responsible for the synthesis of
      poly-N-acetyllactosamine (polyLacNAc) in glycans, and beta3GnT-5 participating in
      the syntheses of sphingoglycolipids were studied in leukemia cell lines during
      differentiation using RT-PCR method. beta3GnT-2 and beta3GnT-8 distribute widely
      in six myeloid and monocytoid leukemia cell lines with different abundances,
      while beta3GnT-4 was only present in NB4 cells. ATRA (all-trans retinoic acid)
      and dimethylsulfoxide (DMSO), which induce the differentiation of HL-60 and NB4
      (two human acute myeloid leukemia cell lines) to myelocytic lineage, up-regulated
      these two enzymes with various degrees at 2 and 72 h of treatment. In HL-60 cells
      treated with ATRA, the increase of beta3GnT-8 was more than beta3GnT-2, while in
      NB4 cells treated with DMSO, the increase of beta3GnT-2 was more than beta3GnT-8.
      However, when HL-60 and NB4 were differentiated to monocytic lineage induced by
      phorbol 12-myristate 13-acetate the expressions of beta3GnT-2 and beta3GnT-8
      showed no alterations or the increase of expressions was far less than those in
      myelocytic differentiation. By means of FITC-labeled tomato lectin affinity
      staining and flow-cytometry, it was found that the product of beta3GnT-2 and -8,
      polyLacNAc was also increased on the cell surface of HL-60 and NB4 treated with
      ATRA or DMSO, but unchanged when treated with PMA. These results were in
      accordance with the up-regulation of the mRNAs of beta3GnT-2 and -8. The
      expression of beta3GnT-5, however, was not changed both in myelocytic and
      monocytic differentiations. The difference in the up-regulation of beta3GnT-2 and
      -8, especially their products may become a useful index to discriminate the
      myelocytic and monocytic differentiation of leukemia cells.

PMID- 21720769
TI  - A disappearing neonatal skin lesion.
AB  - A preterm baby girl was noted at birth to have a firm, raised, non-tender skin
      lesion located over her right hip. She developed three similar smaller lesions on
      her ear, buttock and right knee. All lesions had resolved by 2 months of age.

PMID- 21720770
TI  - Differential effects of late-life initiation of low-dose enalapril and losartan
      on diastolic function in senescent Fischer 344 x Brown Norway male rats.
AB  - No proven pharmacological therapies to delay or reverse age-related diastolic
      dysfunction exist. We hypothesized that late-life low-dose (non-blood-pressure
      lowering) angiotensin-converting enzyme inhibition vs. angiotensin II receptor
      blockade would be equally efficacious at mitigating diastolic dysfunction in the
      senescent Fischer 344 * Brown Norway rat. Enalapril (10 mg/kg/day; n = 9)
      initiated at 24 months of age and continued for 6 months, increased myocardial
      relaxation (e'), reduced Doppler-derived indices of filling pressure (E/e'),
      favorably lowered the ratio of phospholamban-SERCA2 and reduced oxidative stress
      markers, Rac1 and nitrotyrosine, in aged hearts. Treatment with losartan (15
      mg/kg/day; n = 9) similarly mitigated signs of cardiac oxidative stress, but
      impairments in diastolic function persisted when compared with untreated rats (n
      = 7). Our findings favor the idea that the lusitropic benefit of low-dose
      angiotensin-converting enzyme inhibitor initiated late in life may be related to
      an antioxidant-mediated modulation of SERCA2, resulting in improved relaxation
      rather than via overt effects on cardiac structure or blood pressure.

PMID- 21720771
TI  - Distribution of the activity of the angiotensin-converting enzyme in the rat
      aorta and changes in the activity with aging and by the action of L-NAME.
AB  - The activity of the angiotensin-converting enzyme (ACE) of the inner surface (the
      endothelium surface) of rat aorta sections has been studied depending on their
      distance from the aortic arch, age of rats, and the duration of treatment of rats
      with the NO synthase inhibitor, N (omega)-nitro-L-arginine (L-NAME). The activity
      of ACE of aorta sections was determined by measuring the hydrolysis of hippuryl-L
      histidyl-L-leucine and was expressed as picomoles of Hip-His-Leu hydrolyzed per
      minute per square millimeter of the endothelium surface. It was found that the
      ACE activity considerably varies along the aorta of young rats. This variability
      decreases with increasing age of rats and by the action of L-NAME. The average
      ACE activity in the aorta increases with the age of rats and with increasing time
      of L-NAME treatment. Enalapril normalizes the distribution of the ACE activity
      along the aorta and decreases the average ACE activity. The changes in the
      distribution of the ACE activity along the aorta and in the average ACE activity
      in the aorta with increasing age of the rat and by the action of L-NAME may play
      a role in the development of atherosclerosis of vessels on aging and the
      inhibition of formation of nitric oxide.

PMID- 21720772
TI  - Specific PCR to identify the heavy-metal-resistant bacterium Cupriavidus
      metallidurans.
AB  - The aim of this study is to develop a polymerase chain reaction (PCR) assay for
      rapid detection of Cupriavidus metallidurans. PCR primers targeting the Signal
      transduction histidine kinase gene were designed and designated Cm-F1/Cm-R1.
      Strains of C. metallidurans were positively identified. The size of the PCR
      products was 437 bp, as expected. This PCR method enables monitoring of
      industrial, environmental and clinical sources for presence of C. metallidurans.

PMID- 21720773
TI  - Biochemical and kinetic characterization of GH43 beta-D-xylosidase/alpha-L
      arabinofuranosidase and GH30 alpha-L-arabinofuranosidase/beta-D -xylosidase from
      rumen metagenome.
AB  - The present study focuses on characterization of two hemicellulases, RuXyn1 and
      RuXyn2, from rumen bacterial metagenome and their capabilities for degradation of
      xylans. Glycosyl hydrolase (GH) family 43 beta-D -xylosidase/alpha-L 
      arabinofuranosidase RuXyn1 can hydrolyze p-nitrophenyl-beta-D -xylopyranoside
      (pNPX), p-nitrophenyl-alpha-L -arabinofuranoside (pNPA), and xylo-oligosaccharide
      substrates, while GH30 1,5-alpha-L -arabinofuranosidase/beta-D -xylosidase
      RuXyn2, the first alpha-L -arabinofuranosidase assigned to this GH family, shows
      activities towards 1,5-alpha-L -arabinobiose and pNPX substrates but no activity
      for pNPA. Kinetic analysis for aryl-glycosides revealed that RuXyn2 had higher
      catalytic efficiency than RuXyn1 toward pNPX substrate. RuXyn1 shows high
      synergism with endoxylanase, elevating by 73% the reducing sugars released from
      brichwood xylans, and converted most intermediate xylo-oligosaccharide
      hydrolysate into xylose. The high xylose conversion capability of RuXyn1 suggests
      it has potential applications in enzymatic production of xylose and improvement
      of hemicellulose saccharification for production of biofuels. RuXyn2 shows no
      obviously synergistic effect in the endoxylanase-coupled assay for enzymatic
      saccharification of xylan. Further cosmid DNA sequencing revealed a neighboring
      putative GH43 alpha-L -arabinofuranosidase RuAra1 and two putative GH3 beta
      xylosidase/arabinosidases, RuXyn3 and RuXyn5, downstream of RuXyn2, indicating
      that this hemicellulase gene cluster may be responsible for production of end
      product, xylose and arabinose, from hemicellulose biomass.

PMID- 21720774
TI  - Enzymatic production of 2-amino-2,3-dimethylbutyramide by cyanide-resistant
      nitrile hydratase.
AB  - A novel enzymatic route for the synthesis of 2-amino-2,3-dimethylbutyramide
      (ADBA), important intermediate of highly potent and broad-spectrum imidazolinone
      herbicides, from 2-amino-2,3-dimethylbutyronitrile (ADBN) was developed. Strain
      Rhodococcus boritolerans CCTCC M 208108 harboring nitrile hydratase (NHase)
      towards ADBN was screened through a sophisticated colorimetric screening method
      and was found to be resistant to cyanide (5 mM). Resting cells of R. boritolerans
      CCTCC M 208108 also proved to be tolerant against high product concentration (40
      g l(-1)) and alkaline pH (pH 9.3). A preparative scale process for continuous
      production of ADBA in both aqueous and biphasic systems was developed and some
      key parameters of the biocatalytic process were optimized. Inhibition of NHase by
      cyanide dissociated from ADBN was successfully overcome by temperature control
      (at 10 degrees C). The product concentration, yield and catalyst productivity
      were further improved to 50 g l(-1), 91% and 6.3 g product/g catalyst using a
      30/70 (v/v) n-hexane/water biphasic system. Furthermore, cells of R. boritolerans
      CCTCC M 208108 could be reused for at lease twice by stopping the continuous
      reaction before cyanide concentration rose to 2 mM, with the catalyst
      productivity increasing to 12.3 g product/g catalyst. These results demonstrated
      that enzymatic synthesis of ADBA using whole cells of R. boritolerans CCTCC M
      208108 showed potential for industrial application.

PMID- 21720775
TI  - Poly(beta-L-malic acid) production by diverse phylogenetic clades of
      Aureobasidium pullulans.
AB  - Poly(beta-L-malic acid) (PMA) is a natural biopolyester that has pharmaceutical
      applications and other potential uses. In this study, we examined PMA production
      by 56 strains of the fungus Aureobasidium pullulans representing genetically
      diverse phylogenetic clades. Thirty-six strains were isolated from various
      locations in Iceland and Thailand. All strains from Iceland belonged to a newly
      recognized clade 13, while strains from Thailand were distributed among 8 other
      clades, including a novel clade 14. Thirty of these isolates, along with 26
      previously described strains, were examined for PMA production in medium
      containing 5% glucose. Most strains produced at least 4 g PMA/L, and several
      strains in clades 9, 11, and 13 made 9-11 g PMA/L. Strains also produced both
      pullulan and heavy oil, but PMA isolated by differential precipitation in ethanol
      exhibited up to 72% purity with no more than 12% contamination by pullulan. The
      molecular weight of PMA from A. pullulans ranged from 5.1 to 7.9 kDa. Results
      indicate that certain genetic groups of A. pullulans are promising for the
      production of PMA.

PMID- 21720776
TI  - Pseudoxanthomonas bacteria that drive deposit formation of wood extractives can
      be flocculated by cationic polyelectrolytes.
AB  - Runnability problems caused by suspended bacteria in water using industries,
      have, in contrast to biofilms, received little attention. We describe here that
      Pseudoxanthomonas taiwanensis, a wide-spread and abundant bacterium in paper
      machine water circuits, aggregated dispersions of wood extractives ("pitch") and
      resin acid, under conditions prevailing in machine water circuits (10(9) cfu ml(
      1), pH 8, 45 degrees C). The aggregates were large enough (up to 50 MUm) so that
      they could be expected to clog wires and felts and to reduce dewatering of the
      fiber web. The Pseudoxanthomonas bacteria were negatively charged over a pH range
      of 3.2-10. Cationic polyelectrolytes of the types used as retention aids or
      fixatives to flocculate "anionic trash" in paper machines were effective in
      flocculating the Pseudoxanthomonas bacteria. The polyelectrolyte most effective
      for this purpose was of high molecular weight (7-8 * 10(6) g mol(-1)) and low
      charge density (1 meq g(-1)), whereas polyelectrolytes that effectively zeroed
      the electrophoretic mobility (i.e., neutralized the negative charge) of the
      bacterium were less effective in flocculating the bacteria. Based on the results,
      we concluded that the polyelectrolytes functioning by bridging mechanism, rather
      than by neutralization of the negative charge, may be useful as tools for
      reducing harmful deposits resulting from interaction of bacteria with wood
      extractives in warm water industry.

PMID- 21720777
TI  - Radiation exposure and risk-benefit analysis in cancer screening using FDG-PET:
      results of a Japanese nationwide survey.
AB  - OBJECTIVE: The aim of this study was to estimate radiation exposure and evaluate
      the risks and benefits of 18F-fluorodeoxyglucose positron emission tomography
      (FDG-PET) in cancer screening. METHODS: A nationwide survey of FDG-PET cancer
      screening was conducted in 2006, and the results were analyzed with a common
      index, "extension/shortening of the average life expectancy." RESULTS: The
      average estimated effective dose was 4.4 mSv (male 4.7 mSv; female 4.0 mSv) for
      dedicated PET and 13.5 mSv (male 14.2 mSv; female 12.8 mSv) for PET/computed
      tomography (CT). The risk-benefit break-even age from the viewpoint of radiation
      exposure was in the 40s for men and 30s for women for dedicated PET and in the
      50s for men and 50s (variable injection dose) or 60s (constant injection dose)
      for women for PET/CT. CONCLUSIONS: FDG-PET cancer screening is beneficial for
      examinees above the break-even ages. The risks and benefits should be explained
      to examinees because of the larger radiation used in cancer FDG-PET screening
      compared with other X-ray tests.

PMID- 21720778
TI  - 18F-fluoromisonidazole positron emission tomography before treatment is a
      predictor of radiotherapy outcome and survival prognosis in patients with head
      and neck squamous cell carcinoma.
AB  - OBJECTIVE: To evaluate the usefulness of [(18)F]fluoromisonidazole ([(18)F]FMISO)
      positron emission tomography (PET) prior to the treatment of head and neck
      squamous cell carcinoma. METHODS: Seventeen patients with untreated HNSCC
      underwent pretreatment [(18)F]FMISO PET. Six of them underwent definitive surgery
      and the remaining 11 definitive (chemo-)radiotherapy. We evaluated 30 lesions
      from the 17 patients. SUVmax and tumor-to-muscle ratios (TMR) were measured as
      hypoxia indicators. Tumors equal to or above the median value were defined as
      tumor with high uptake of [(18)F]FMISO and those below as tumor with low uptake
      of [(18)F]FMISO in both indicators. Local control rates with radiotherapy, event
      free survival and disease-specific survival (DSS) rates with radiotherapy or
      operation were compared. RESULT: [(18)F]FMISO-PET imaging of 30 lesions resulted
      in a SUVmax median value of 2.3 and a TMR median value of 1.3. Local control
      rates with radiotherapy (20-month median follow-up duration) were significantly
      lower in the tumor group with high uptake of [(18)F]FMISO compared to the tumor
      group with low uptake of [(18)F]FMISO using either SUVmax or TMR as the hypoxic
      indicator (P = 0.02 and 0.04, respectively). DSS rate with radiotherapy or
      operation (21-month median follow-up duration) was significantly lower in the
      patient group with high uptake of [(18)F]FMISO compared to the patient group with
      low uptake of [(18)F]FMISO defined by SUVmax (P = 0.04), but was not by TMR (P =
      0.57). CONCLUSIONS: Radiotherapy outcome and survival prognosis (radiotherapy or
      operation) in HNSCC may be predicted by carrying out [(18)F]FMISO PET before
      treatment.

PMID- 21720779
TI  - Impact of chronic kidney disease and stress myocardial perfusion imaging as a
      predictor of cardiovascular events.
AB  - BACKGROUND: Stress myocardial perfusion imaging (MPI) is an established means of
      predicting cardiovascular events and is suitable in chronic kidney disease (CKD)
      patients. We aimed to evaluate the prognostic value of CKD parameters and an
      abnormal stress MPI for cardiovascular events. METHODS: A total of 495 patients
      with suspected coronary artery disease (CAD) or history of CAD including 130 CKD
      patients not undergoing hemodialysis, underwent stress MPI (313 males, mean age
      70 years) and were followed up for 14 months (mean period). CKD was defined as an
      estimated GFR of <60 ml/min/1.73 m(2) and/or persistent proteinuria.
      Cardiovascular events were defined as sudden cardiac death, acute coronary
      syndrome and congestive heart failure requiring hospitalization. RESULTS:
      Cardiovascular events occurred in 41 (8.3%) patients. Multivariate Cox regression
      analysis indicated that CKD [hazard ratio (HR) = 3.76, p < 0.001] and a stress
      MPI summed difference score (SDS) of >=2 (HR = 3.78, p < 0.001) were independent
      predictors of cardiovascular events; CKD plus abnormal stress MPI was also a
      strong predictor of cardiovascular events (non-CKD and SDS <2 vs. CKD and SDS
      >=2, HR = 15.9, p < 0.001). CONCLUSION: Both CKD and myocardial ischemia detected
      by stress MPI are independent predictors for cardiovascular events. Coexistence
      of CKD and myocardial ischemia detected by stress MPI is more useful for short
      term risk stratification of cardiovascular events.

PMID- 21720780
TI  - Internal radiotherapy techniques using radiolanthanide praseodymium-142: a review
      of production routes, brachytherapy, unsealed source therapy.
AB  - Radionuclides of rare earth elements are gaining importance as emerging
      therapeutic agents in nuclear medicine. beta(-)-particle emitter 142Pr [T (1/2) =
      19.12 h, E(-)beta = 2.162 MeV (96.3%), Egamma = 1575 keV (3.7%)] is one of the
      praseodymium-141 (100% abundant) radioisotopes. Production routes and therapy
      aspects of 142Pr will be reviewed in this paper. However, 142Pr produces via
      141Pr(n, gamma) 142Pr reaction by irradiation in a low-fluence reactor; 142Pr
      cyclotron produced, could be achievable. 142Pr due to its high beta(-)-emission
      and low specific gamma gamma-emission could not only be a therapeutic
      radionuclide, but also a suitable radionuclide in order for biodistribution
      studies. Internal radiotherapy using 142Pr can be classified into two sub
      categories: (1) unsealed source therapy (UST), (2) brachytherapy. UST via 142Pr
      HA and 142Pr-DTPA in order for radiosynovectomy have been proposed. In addition,
      142Pr Glass seeds and 142Pr microspheres have been utilized for interstitial
      brachytherapy of prostate cancer and intraarterial brachytherapy of arteriovenous
      malformation, respectively.

PMID- 21720781
TI  - Examining the relationships between acculturation orientations, perceived and
      actual norms, and drinking behaviors of short-term american sojourners in foreign
      environments.
AB  - As little research has examined factors influencing increased and heavy drinking
      behavior among American sojourners abroad, this study was designed to examine how
      acculturation orientations (i.e., separation versus assimilation), host country
      per capita drinking rates, and perceptions about the drinking behavior among
      other sojourners and natives in the host country predicted alcohol risk abroad. A
      sample of 216 American college students completing study abroad programs
      completed a pre-abroad questionnaire to document their pre-abroad drinking
      levels, followed by a post-return questionnaire to assess drinking while abroad,
      acculturation orientations and perceived norms of drinking behavior within the
      foreign environment. A dichotomous variable was created to compare United States
      (U.S.) per capita drinking rates with those of the host country. Hierarchical
      repeated-measures ANOVAs examined the changes in drinking from pre-abroad to
      abroad levels. Participants studying in countries with higher drinking rates than
      the U.S. and those with higher perceptions about the drinking behavior in the
      country increased their drinking to a greater extent. Those with higher
      separation acculturation orientations and greater perceptions drank at heavier
      levels while abroad. Participants with a greater assimilation orientation and
      higher perceptions about native drinking, as well as those with a greater
      separation orientation and higher perceptions about other students' alcohol use
      drank the heaviest while abroad. These findings have implications for future
      preventive work with American students and other sojourning groups to promote pre
      abroad knowledge of more accurate drinking norms and greater engagement in the
      culture to potentially prevent increased and heavier drinking.

PMID- 21720782
TI  - Effects of a social-emotional and character development program on the trajectory
      of behaviors associated with social-emotional and character development: findings
      from three randomized trials.
AB  - The effects of a school-based social-emotional and character development program,
      Positive Action, on the developmental trajectory of social-emotional and
      character-related behaviors was evaluated using data from three school-based
      randomized trials in elementary schools. Results come from 1) 4 years of data
      from students in 20 Hawai'i schools, 2) 3 years of data from students in 14
      schools in Chicago and 3) 3 years of data from students in 8 schools in a
      southeastern state. Random intercept, multilevel, growth-curve analyses showed
      that students in both control and Positive Action schools exhibited a general
      decline in the number of positive behaviors associated with social-emotional and
      character development that were endorsed. However, the Positive Action
      intervention significantly reduced these declines in all three trials. Taken
      together, these analyses 1) give insight into the normative trajectory of
      behaviors associated with social-emotional and character development and 2)
      provide evidence for the effectiveness of Positive Action in helping children
      maintain a relatively beneficial developmental trajectory.

PMID- 21720783
TI  - Contribution of family violence to the intergenerational transmission of
      externalizing behavior.
AB  - Research finds that early antisocial behavior is a risk for later intimate
      partner violence (IPV) perpetration and victimization, and that children's
      exposure to their parents' IPV is a risk for subsequent behavior problems. This
      study tests whether intimate violence (IPV) between partners contributes
      independently to the intergenerational transmission of antisocial behavior, using
      the Children in the Community Study, a representative sample (N = 821) followed
      for over 25 years in 6 assessments. The present study includes a subsample of
      parents (N = 678) and their offspring (N = 396). We test the role of three
      mechanisms by which IPV may influence child antisocial behavior-parental
      psychopathology, parenting practices, and child self-regulation. Results suggest
      that IPV independently increased the risk for offspring externalizing problems,
      net of the effects of parental history of antisocial behavior and family
      violence. IPV also increased the risk for parental post traumatic stress disorder
      (PTSD) and alcohol use disorder 2 years later, but not for major depressive
      disorder. Alcohol use disorder independently increased the risk for offspring
      externalizing behavior, but IPV continued to predict offspring externalizing net
      of parental alcohol use. Parenting, particularly low satisfaction with the child,
      was significantly associated with both IPV and externalizing behavior, but did
      not mediate the effects of IPV on externalizing. IPV predicted higher levels of
      emotional expressivity, aggression and hostile reactivity, and depressive mood in
      offspring. Implications for future research and prevention are discussed.

PMID- 21720784
TI  - The relationship between serum levels of Zn and Cu and severity of coronary
      atherosclerosis.
AB  - The essential trace elements play important roles in the maintainance of the
      normal structure and physiology of cells. Several research groups have
      demonstrated that they also play important roles in states of cardiovascular
      diseases. Our aim is to investigate whether there is a relationship between trace
      elements (Zn and Cu) and the degree of atherosclerosis. The sample consisted of
      67 patients with coronary artery disease and 26 clinically healthy individuals.
      Ninety-three subjects were separated into four groups according to their Gensini
      scores, the number of diseased vessels, the presence of acute coronary syndrome,
      and ejection fraction. Each group was divided into three subgroups, and serum
      zinc and copper levels were measured for each individual. The serum levels of
      zinc and copper were found to be significantly lower in patients with
      atherosclerosis than in the control group, but there were no significant
      differences in the serum levels of Cu and Zn between severe atherosclerosis and
      mild atherosclerosis. In Spearman's rank correlation, the zinc and copper levels
      were correlated with the Gensini score and the number of diseased vessels. The
      present study revealed a relationship between the serum levels of zinc and copper
      and atherosclerosis, but not between these levels and the severity of the
      disease.

PMID- 21720785
TI  - Putative role of the adenosine A(3) receptor in the antiproliferative action of N
      (6)-(2-isopentenyl)adenosine.
AB  - We tested a panel of naturally occurring nucleosides for their affinity towards
      adenosine receptors. Both N (6)-(2-isopentenyl)adenosine (IPA) and racemic zeatin
      riboside were shown to be selective human adenosine A(3) receptor (hA(3)R)
      ligands with affinities in the high nanomolar range (K (i) values of 159 and 649
      nM, respectively). These values were comparable to the observed K (i) value of
      adenosine on hA(3)R, which was 847 nM in the same radioligand binding assay. IPA
      also bound with micromolar affinity to the rat A(3)R. In a functional assay in
      Chinese hamster ovary cells transfected with hA(3)R, IPA and zeatin riboside
      inhibited forskolin-induced cAMP formation at micromolar potencies. The effect of
      IPA could be blocked by the A(3)R antagonist VUF5574. Both IPA and reference
      A(3)R agonist 2-chloro-N (6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (Cl
      IB-MECA) have known antitumor effects. We demonstrated strong and highly similar
      antiproliferative effects of IPA and Cl-IB-MECA on human and rat tumor cell lines
      LNCaP and N1S1. Importantly, the antiproliferative effect of low concentrations
      of IPA on LNCaP cells could be fully blocked by the selective A(3)R antagonist
      MRS1523. At higher concentrations, IPA appeared to inhibit cell growth by an
      A(3)R-independent mechanism, as was previously reported for other A(3)R agonists.
      We used HPLC to investigate the presence of endogenous IPA in rat muscle tissue,
      but we could not detect the compound. In conclusion, the antiproliferative
      effects of the naturally occurring nucleoside IPA are at least in part mediated
      by the A(3)R.

PMID- 21720786
TI  - Hard ticks on one-humped camel (Camelus dromedarius) and their seasonal
      population dynamics in southeast, Iran.
AB  - The primary objective of this study was to determine the diversity and intensity
      of ticks found on camels (Camelus dromedarius) and their seasonal population
      dynamics in Kerman, southeast of Iran. For this purpose, a total of 426 tick
      specimens were collected from 217 infested camels in southeast of Iran during
      activating seasons of ticks (April 2009 to March 2010). The species collected
      from camel were Hyalomma dromedarii (84.7%), Hyalomma marginatum (8.7%), Hyalomma
      anatolicum excavatum (5.4%), and Hyalomma anatolicum anatolicum (1.2%). The
      highest seasonal activities occurred in summer. The ratio of male ticks was more
      than female ticks. H. dromedarii was the predominant tick species and accounted
      for 84.7% of the ticks.

PMID- 21720787
TI  - Preliminary comparison of different immune and production components in local and
      imported Saanen goats reared under a sub-tropical environment.
AB  - Three objectives were included in this research work. The first objective
      compared different immune components in healthy mature males, mature females, and
      female kids of local and imported Saanen goats, reared under a sub-tropical
      environment. The significantly differing immune components were the blood
      monocyte percent, blood CD8 count, and the total white blood cell count. The
      second objective compared the performance of Saanen versus local does. The means
      of the milk yield and prolificacy of the imported Saanen does were significantly
      higher than those of the local does (p<0.05). The third objective compared the
      immune responses (hemagglutination-HA titers) and complement fixation (CF) titers
      in mature does of the two breeds to chicken red blood cells (c-RBC). The HA
      titers showed a significant seroconversion only in imported Saanen (p<0.05) but
      not in local does; however, the CF titers increased significantly at 4 weeks
      following priming with c-RBC in local (p<0.05) but not in the imported Saanen
      does. The impact of the differences in blood immune components and responses to
      antigens in the compared goats on protection potential against prevalent diseases
      in the sub-tropical zone of the eastern Mediterranean countries is discussed.

PMID- 21720788
TI  - Estradiol supplementation during the luteal phase in poor responder patients
      undergoing in vitro fertilization: a randomized clinical trial.
AB  - PURPOSE: This study was designed to evaluate the effects of adding Estradiol (E2)
      supplementation to progesterone (P) on improvement of pregnancy outcomes in poor
      responder patients who underwent in vitro fertilization (IVF). METHODS: In a
      prospective randomized clinical trial, 118 poor responder patients, older than 38
      years without contraindications of estradiol consumption from Infertility clinic
      of a university hospital were randomly divided (by computerized software) into
      two groups. Control group (59 patients) received only P and intervention group
      (59 patients) received P and E2 (4 mg/d). Supplementation was done with 4 mg E2
      in the luteal phase. Fertilization rate, implantation rate, biochemical and
      clinical pregnancy rates, abortion rate, ongoing pregnancy, multiple pregnancy
      and ectopic pregnancy rates were documented for those who completed the study
      protocol in each group (per protocol analysis) and compared between groups.
      RESULT: Fifty five patients in control group and 53 patients in intervention
      group successfully completed the study protocol. Treatment outcomes were not
      significantly different between two groups. CONCLUSION: For poor responder women
      who underwent IVF, addition of E2 to P supplementation could not significantly
      improve pregnancy outcomes.

PMID- 21720789
TI  - Breast cancer classification based on advanced multi dimensional fuzzy neural
      network.
AB  - Breast cancer is the cause of the most common cancer death in women. Early
      detection of the breast cancer is an effective method to reduce mortality. Fuzzy
      Neural Networks (FNN) comprises an integration of the merits of neural and fuzzy
      approaches, enabling one to build more intelligent decision-making systems. But
      increasing the number of inputs causes exponential growth in the number of
      parameters in Fuzzy Neural Networks (FNN) and computational complexity increases
      accordingly. This phenomenon is named as "curse of dimensionality". The
      Hierarchical Fuzzy Neural Network (HFNN) and the Fuzzy Gaussian Potential Neural
      Network (FGPNN) are utilized to deal this problem. In this study, the HFNN and
      FGPNN by using new training algorithm, are applied to the Wisconsin Breast Cancer
      Database to classify breast cancer into two groups; benign and malignant lesions.
      The HFNN consists of hierarchically connected low-dimensional fuzzy neural
      networks. It can use fewer rules and parameters to model nonlinear system.
      Moreover, the FGPNN consists of Gaussian Potential Function (GPF) used in the
      antecedent as the membership function. When the number of inputs increases in
      FGPNN, the number of fuzzy rules does not increase. The performance of HFNN and
      FGPNN are evaluated and compared with FNN. Simulation results show the
      effectiveness of these methods even with less rules and parameters in performance
      result. These methods maintain the accuracy of original fuzzy neural system and
      have high interpretability by human in diagnosis of breast cancer.

PMID- 21720790
TI  - Proanthocyanidins inhibit iron absorption from soybean (Glycine max) seed
      ferritin in rats with iron deficiency anemia.
AB  - The objective of this study was to evaluate the effect of proanthocyanidins (PAs)
      on iron uptake from soybean seed ferritin (SSF) crude by rats with iron
      deficiency anemia (IDA) for the first time. Six groups of Sprague-Dawley (SD)
      rats (n = 10) were used, which contain (1) SSF crude group; (2) SSF crude + PAs
      group; (3) PAs group; (4) FeSO(4) group; (5) iron deficiency control group; and
      (6) control group. The bioavailability of iron was examined by measuring
      hemoglobin (Hb) concentration value, red blood cell (RBC) numbers, and serum iron
      stores. After 8 weeks, Hb concentration was almost recovered to the normal level
      upon feeding SSF crude or FeSO(4) to rats. In contrast, Hb concentration was
      recovered to less extent when SSF crude plus PAs was used instead of SSF crude
      alone (P < 0.05). A similar profile was observed with these three sample groups
      when serum iron and RBC were used as parameters. All rats in PAs group died at
      the 8th week. Taken together, all these results demonstrated that PAs inhibited
      iron uptake of rats from SSF, and are toxic for rats with IDA.

PMID- 21720791
TI  - GABAergic neurons from mouse embryonic stem cells possess functional properties
      of striatal neurons in vitro, and develop into striatal neurons in vivo in a
      mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disease where GABAergic medium
      spiny neurons (MSNs) in the striatum degenerate. Embryonic stem cell-derived
      neural transplantation may provide an appropriate therapy for HD. Here we aimed
      to develop a suitable protocol to obtain a high percentage of functional
      GABAergic neurons from mouse embryonic stem cells (mESCs), and then tested their
      differentiation potential in vivo. The monolayer method was compared with the
      embryoid body and five stage method for its efficiency in generating GABAergic
      neurons from mESCs. All three methods yielded a similar percentage of GABAergic
      neurons from mESCs. Monolayer method-derived GABAergic neurons expressed the MSN
      marker dopamine- and cyclic AMP-regulated phosphoprotein (DARPP32). The
      pluripotent stem cell population could be eliminated in vitro by treating cells
      with puromycin and retinoic acid. Using patch-clamp recordings, the functional
      properties of GABAergic neurons derived from mESCs were compared to GABAergic
      neurons derived from primary lateral ganglionic eminence. Both types of neurons
      showed active membrane properties (voltage-gated Na(+) and K(+) currents, Na(+)
      dependent action potentials, and spontaneous postsynaptic currents) and possessed
      functional glutamatergic receptors and transporters. mESC-derived neural
      progenitors were transplanted into a mouse model of HD. Grafted cells
      differentiated to mature neurons expressing glutamate decarboxylase, dopamine
      type 1 receptors, and DARPP32. Also, neural precursors and dividing populations
      were found in the grafts. In summary, mESCs are able to differentiate efficiently
      into functional GABAergic neurons using defined in vitro conditions, and these
      survive and differentiate following grafting to a mouse model of HD.

PMID- 21720792
TI  - Evaluation of potential biomarkers for the discrimination of bacterial and viral
      infections.
AB  - PURPOSE: Timely knowledge of the bacterial etiology and localization of infection
      are important for empirical antibiotic therapy. Thus, the goal of this study was
      to evaluate routinely used biomarkers together with novel laboratory parameters
      in the diagnosis of infection. METHODS: In this prospective study, 54 adult
      patients with bacterial infections admitted to the Department of Infectious
      Diseases were included. For comparison, 27 patients with viral infections were
      enrolled. In these patients, white blood cell (WBC) counts, differential blood
      counts, serum levels of procalcitonin (PCT), IL-1beta, IL-6, IL-8, IL-10, IL-12,
      TNF-alpha, IFN-gamma, soluble CD14 (sCD14), heparin-binding protein (HBP),
      cortisol (Cort), and monocyte surface expression of TLR2, TLR4, HLA-DR, and CD14
      were analyzed. Also, these biomarkers were evaluated in 21 patients with acute
      community-acquired bacterial pneumonia (CABP), as well as in 21 patients with
      pyelonephritis and urosepsis. RESULTS: The highest sensitivity and specificity
      (expressed as the area under the curve [AUC]) for bacterial infection were
      observed in serum concentration of PCT (0.952), neutrophil and lymphocyte counts
      (0.852 and 0.841, respectively), and serum levels of HBP (0.837), IL-6 (0.830),
      and Cort (0.817). In addition, the serum levels of IFN-gamma and Cort were
      significantly higher and IL-8 levels were lower in CABP when compared to
      pyelonephritis or urosepsis. CONCLUSIONS: From the novel potential biomarkers,
      only PCT demonstrated superiority over the routine parameters in the
      differentiation of bacterial from viral infections. However, some of the novel
      parameters should be further evaluated in larger and better characterized cohorts
      of patients in order to find their clinical applications.

PMID- 21720793
TI  - Group treatment for postpartum depression: a systematic review.
AB  - Postpartum depression (PPD) is a serious public health problem affecting 10% to
      15% of women during the first year after delivery with negative consequences for
      both mother and infant. There is a need for evidence-based interventions to treat
      this disorder. Thus, the purpose of this study was to systematically review the
      literature regarding group treatment for PPD to determine the current state of
      knowledge regarding the efficacy of this treatment modality for reducing
      depressive symptoms in postpartum women. A systematic search of published and
      unpublished literature using the electronic databases Medline, CINAHL, PsycINFO,
      Cochrane Database, Cochrane Central Register of Controlled Trials, Current
      Controlled Trials, and Dissertation Abstracts through March 2011, supplemented by
      hand searches, identified 11 studies which met inclusion criteria: six were
      randomized controlled trials and five were non-randomized trials which utilized
      non-equivalent control or comparison groups. All but one study showed
      statistically significant improvement in depression scores from pretreatment to
      post-treatment, suggesting that group treatment is effective in reducing PPD
      symptoms. The review provides initial support for the role of group therapy in
      the treatment of PPD; however, caution is advised in making generalized
      interpretations of the findings as there was considerable heterogeneity of the
      studies included and the quality of the studies was mixed. Overall, the review
      reveals significant gaps in the current evidence base for group treatment for PPD
      and recommendations for further research is discussed.

PMID- 21720794
TI  - Negative trial results are important to understand the mechanisms of
      multimodality therapy in gastric cancer.

PMID- 21720795
TI  - [Modern angiographic diagnostic techniques in the catheter laboratory].
AB  - Even at the beginning of the twenty-first century angiography still is the gold
      standard for imaging coronary arteries. Many limitations of this technique have
      facilitated advancements, such as quantitative coronary angiography and 3
      dimensional reconstruction. The use of intravascular ultrasound has enabled a
      transmural in vivo imaging of the coronary arteries while creating cross
      sectional images of the vessel wall. This led to a better evaluation of vascular
      plaques and the surrounding structures of the vessel. Optical coherence
      tomography is a new modality based on infrared light, which provides intraluminal
      and extraluminal imaging of vessels with a resolution of 10-20 um, which is
      better than intravascular ultrasound (IVUS). However even this modern diagnostic
      tool is limited in the assessment of the relevance of an epicardial stenosis.
      Evaluation of the fractional flow reserve is a pathophysiological test, which
      measures the pressure before and after an epicardial stenosis and is able to
      assess the functional condition of a vessel with a high sensitivity and
      specificity. The so-called C-arm computed tomography (CACT; DynaCT Cardiac;
      Siemens, Erlangen, Germany) is a new application of an intraprocedural technique
      based on rotation of an x-ray source around a patient. It is able to generate
      information similar to that created by conventional computed tomography (CT)
      scans and offers the possibility to significantly enhance angiographic diagnostic
      modalities.

PMID- 21720796
TI  - Nanomaterials in controlled drug release.
AB  - In past years with the advances of chemistry and material sciences, the
      development of nanotechnology brought generations of nanomaterials with specific
      biomedical properties. These include the nanoparticle-based drug delivery,
      nanosized drugs, and nanomaterials for tissue engineering. The present article
      focuses on the use of nanomaterials in controlled drug release. The applications
      of nanomaterials with nano-enabled drug release characteristics brought many
      benefits when compared to the traditional (bulk) materials. We discuss the
      current advances and propose some future directions for the technology
      development.

PMID- 21720797
TI  - Removal of Pb (II) by immobilized and free filaments of marine Oscillatoria sp.
      NTMS01 and Phormidium sp. NTMS02.
AB  - Pb(2+) removal ability of the immobilized and free filaments of marine
      cyanobacteria Oscillatoria sp. NTMS01 and Phormidium sp. NTMS02 was studied using
      batch experiments. Biosorption of lead by immobilized filaments was studied as a
      function of pH (2, 4, 6, 8, 10), contact time (5-180 min) and initial lead
      concentration (1, 3, 5, 7 mg/L) and the removal efficiency of free filaments was
      studied by culturing in the marine medium with the initial concentration (1, 3,
      5, 7 mg/L) at pH 7 and incubated for 10 days. The maximum percentage removal was
      observed at 25 min for immobilized Oscillatoria sp. NTMS01 and 30 min for
      immobilized Phormidium sp. NTMS02. At 4th and 6th day of incubation, 89% and 77%
      removal was observed at 1 mg/L of initial lead concentration by free filaments of
      Oscillatoria sp. NTMS01 and Phormidium sp. NTMS02 respectively and further the
      removal was decreased with increasing concentration. Chlorophyll-a content was
      decreased in a dose dependent manner. About 40 and 50% reduction of chlorophyll-a
      was observed at higher concentration in Oscillatoria sp. NTMS01 and Phormidium
      sp. NTMS02 respectively. The adsorption capacity of immobilized Oscillatoria sp.
      NTMS01 was found to be (Q(max)) 217.39 which is comparatively higher than other
      sorbents. The Pb(2+) removal efficiency was performed as described in terms of
      Langmuir and Freundlich isotherms. These organisms is found to fit better by the
      Langmuir isotherms.

PMID- 21720798
TI  - Framing reflexivity in quality improvement devices in the care for older people.
AB  - Health care organizations are constantly seeking ways to improve quality of care
      and one of the often-posed solutions to deliver 'good care' is reflexivity.
      Several authors stress that enhancing the organizations' and caregivers'
      reflexivity allows for more situated, and therefore better care. Within quality
      improvement initiatives, devices that guarantee quality are also seen as key to
      the delivery of good care. These devices do not solely aim at standardizing work
      practices, but are also of importance in facilitating reflexivity. In this
      article, we study how quality improvement devices position the relationship
      between situated reflection and standardization of work processes. By exploring
      the work of Michel Callon, Michael Lynch, and Lucy Suchman on reflexivity in work
      practices, we study the development and introduction of the Care Living Plan.
      This device aimed to transform care organizations of older people from their
      orientation towards the system of care into organizations that take a client
      centred approach. Our analysis of the construction of specific forms of
      reflexivity in quality devices indicates that the question of reflexivity does
      not need to be opposed to standardization and needs to be addressed not only at
      the level of where reflexivity is organizationally situated and who gets to do
      the reflecting, but also on the content of reflexivity, such as what are the
      issues that care workers can and cannot reflect upon. In this paper we point out
      the theoretical importance of a more detailed empirical study of the framing of
      reflexivity in care practices.

PMID- 21720799
TI  - What we have learned from Fukushima.

PMID- 21720800
TI  - Treatment for primary spinal atypical teratoid/rhabdoid tumor.

PMID- 21720801
TI  - Gene expression profiling of mouse growth plate cartilage by laser
      microdissection and microarray analysis.

PMID- 21720802
TI  - Optimal supplementation of dexamethasone for clinical purposed expansion of
      mesenchymal stem cells for bone repair.
AB  - BACKGROUND: Although mesenchymal stem cells (MSCs) are generally considered to
      represent a very promising tool for bone repair, no optimal protocol has yet been
      developed for the isolation and expansion of these cells for large-scale clinical
      applications. METHODS: Mesenchymal stem cells were supplemented with four
      different concentrations of dexamethasone: 0 M (Con), 0.2 * 10(-8) M (D0.2), 1.0
      * 10(-8) M (D1.0) and 5.0 * 10(-8) M (D5.0); and analyzed every week for 5 weeks
      (P1-P5). Cells were analyzed via an alkaline phosphatase assay, DNA
      quantification, Oil Red stain, and flow cytometry for CD105 and CD90.
      Additionally, P3 and P5 cells were subcutaneously transplanted into nude mice
      after seeding in ceramic cubes. RESULTS: Proliferation of the cells was
      significantly higher in the D0.2 group. Alkaline phosphatase activities remained
      at low levels in the Con and D0.2 groups, but increased to high levels in the
      D1.0 and D5.0 groups as time elapsed. CD105 expression at P5 was lower than at
      P1, P2 and P3. Adipocyte differentiation was highest at P3. At the 8th week, in
      vivo bone formation was enhanced by the MSCs in a dexamethasone-supplemented
      culture for 3 or 5 weeks, and D0.2 was also higher than Con. CONCLUSIONS: The
      supplementation of MSCs under low-level rather than physiological concentrations
      (2 * 10(-9) M) of dexamethasone facilitates the culture expansion of these cells
      for osteogenic purposes by enhancing cell proliferation without diverse
      differentiation, and also promotes bone formation after in vivo transplantation.

PMID- 21720803
TI  - The influence of EPO and hypothermia on the kidneys of rats after perinatal
      asphyxia.
AB  - The aim of this study was to determine the effects of erythropoietin (EPO),
      moderate hypothermia, and a combination thereof on the kidneys of newborn rats
      damaged during perinatal asphyxia. An animal model of perinatal asphyxia (Wistar
      rats) was used in which after birth, newborn rats were divided into four groups
      of 15 animals each: G1, rats exposed only to asphyxia; G2, rats exposed to
      asphyxia and hypothermia (rectal temperature 32 degrees C) and which received EPO
      (darbepoetin alpha) intraperitoneally; G3, rats exposed to asphyxia and
      hypothermia; G4, rats exposed to asphyxia and which received EPO. The rats were
      sacrificed on the 7th day of life and histopathological evaluation of kidneys was
      performed. Damage to the proximal tubules was significantly higher in group G1
      rats than in groups G2, G3, and G4 rats (p < 0.01). Damage to the distal tubules
      was found only in group G1 rats. Histological changes in the proximal tubules
      were more prominent than in the distal tubules (p < 0.01). The immature glomeruli
      zone was less expressed in group G4 rats than in groups G1, G2, and G3 rats (p <
      0.01). Based on these results, we conclude that EPO and hypothermia, as well as
      the combination thereof, have a protective effect on rats' kidneys damaged during
      perinatal asphyxia.

PMID- 21720804
TI  - Bilateral renal artery stenosis and epidermal nevus syndrome in a child.
AB  - Epidermal nevus syndrome is a rare congenital sporadic neuro-ectodermic disorder,
      characterized by the presence of epidermal nevi in association with various
      developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular
      and urogenital systems. We describe a 5-year-old boy with conjunctival
      lipodermoid, cervical and facial sebaceous nevi who presented at 3 years of age
      with hypertension due to bilateral renal artery stenosis together with multiple
      vascular anomalies (aorta, celiac trunk, superior mesenteric artery) as shown by
      magnetic resonance angiography. Systemic arterial hypertension was difficult to
      control despite combined anti-hypertensive drugs and the surgical repair of the
      aortic coarctation.

PMID- 21720805
TI  - Distinct metalloproteinase excretion patterns in focal segmental
      glomerulosclerosis.
AB  - Metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) degrade type IV
      collagen, and represent important tissue remodeling enzymes in several kidney
      disorders. In this study, we measured urinary levels of MMP-2, MMP-9, and the
      tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in patients with
      steroid-sensitive nephrotic syndrome (SSNS, n = 18, median age 5) and focal
      segmental glomerulosclerosis (FSGS, n = 16, median age 15). We found that urinary
      concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly elevated in
      FSGS patients as compared to SSNS in both relapse and remission (p < 0.002).
      Furthermore, urinary levels of these enzymes are increased early on in the FSGS
      disease process (chronic kidney disease stages 1 and 2). The findings from this
      pilot study suggest that MMPs and TIMPs have the potential to represent
      candidate, early non-invasive biomarkers for diagnosis and/or response to
      therapy. In addition, they may represent therapeutic targets for preventing
      chronic kidney disease progression in FSGS.

PMID- 21720807
TI  - Growth-inhibitory effect of neurotrophin-3-secreting adipose tissue-derived
      mesenchymal stem cells on the D283-MED human medulloblastoma cell line.
AB  - Medulloblastoma (MBL), the most common malignant pediatric brain tumor, is
      incurable in about one-third of patients and can lead to long-term disabilities
      despite current multimodal treatments. The purpose of this study was to
      demonstrate in vitro biological effects of neurotrophins-3 (NT-3) on MBL cells
      and to evaluate the growth-inhibitory effect of neurotrophin-3 (NT-3)-secreting
      stem cells on tumor cells. We confirmed by western blotting that D283-MED cells
      express tyrosine kinase C, a specific receptor for NT-3. Analyzing the biological
      effects of NT-3 on MBL cells, we evaluated autophagy, apoptosis, senescence, and
      differentiation of tumor cells with NT-3. The NT-3 induced a concentration
      dependent increase in apoptosis in the tumor cell line (P < 0.001). The high
      concentrations of NT-3 increased the expression of class III beta-tubulin (P <
      0.001) and decreased the expression of Nestin (P < 0.05). NT-3-secreting stem
      cells were produced by nucleofecting pIRES2.EGFP-NT3 into human adipose tissue
      derived mesenchymal stem cells (hAT-MSCs) and their tropic property toward MBL
      cells was confirmed by migration assay. Double-layered co-culture experiments
      with the NT-3-secreting hAT-MSCs and D283-MED MBL cells were performed, and NT-3
      induced cell death was studied by 3-(4,5-dimethylathiazol-2-yl)-2,5-dephenyl
      tetrazolium bromide (MTT) assay. Consequently, the high concentrations of NT-3
      secreting hAT-MSCs significantly (P < 0.05) increased the death of D283-MED cells
      in vitro. The present study demonstrated that both apoptotic cell death and
      neuronal differentiation of tumor cells were the mechanisms of growth-inhibitory
      effect of NT-3-secreting hAT-MSCs on MBL cell line.

PMID- 21720806
TI  - The roles of viruses in brain tumor initiation and oncomodulation.
AB  - While some avian retroviruses have been shown to induce gliomas in animal models,
      human herpesviruses, specifically, the most extensively studied cytomegalovirus,
      and the much less studied roseolovirus HHV-6, and Herpes simplex viruses 1 and 2,
      currently attract more and more attention as possible contributing or initiating
      factors in the development of human brain tumors. The aim of this review is to
      summarize and highlight the most provoking findings indicating a potential
      causative link between brain tumors, specifically malignant gliomas, and viruses
      in the context of the concepts of viral oncomodulation and the tumor stem cell
      origin.

PMID- 21720808
TI  - Salvage treatment with temozolomide in refractory or relapsed primary central
      nervous system lymphoma and assessment of the MGMT status.
AB  - High-dose methotrexate (HD-MTX) is effective in the initial treatment of primary
      central nervous system lymphoma (PCNSL). Because treatment options in patients
      with progressive or recurrent PCNSL are limited, prognosis is poor. Temozolomide,
      a well-tolerated oral alkylating agent that permeates the blood brain barrier
      (BBB), is effective against malignant glioma and recurrent PCNSL. The gene for
      the deoxyribonucleic acid (DNA) repair enzyme O(6)-methylguanine-DNA
      methyltransferase (MGMT), which is closely related to cellular sensitivity to
      alkylating agents, is inactivated by promoter hypermethylation. We evaluated the
      results of temozolomide treatment and the methylation status of the promoter
      region of the MGMT gene in 17 patients (median age 68 years) with refractory or
      relapsed PCNSL. They were immunocompetent and had received initial treatment with
      HD-MTX (3.5 g/m(2)) with or without irradiation. All were treated with
      temozolomide 150-200 mg/m(2), for 5 days in the course of 28 days; treatment was
      continued until disease progression. We observed five complete remissions, five
      partial responses (PRs) with stable disease (SD), and seven with disease
      progression. Median overall survival after the temozolomide treatment was 6.7
      months. One patient manifested grade 3 neutropenia and thrombocytopenia. Eleven
      tumor specimens were available for MGMT analysis. MGMT promoter methylation
      (mMGMT) in the tumor tissue was found in 4 (36.4%), the other seven harbored a
      non-methylated MGMT promoter (nmMGMT). There was no statistically significant
      difference in median overall survival between patients with mMGMT (11.1 months)
      and nmMGMT (6.7 months) (P = 0.63). Although some patients were elderly and had
      been heavily pre-treated, temozolomide resulted in a complete response (CR) in
      29% and was well tolerated without any major toxicity.

PMID- 21720809
TI  - Subcutaneous malignant melanoma of the scalp surgical flap after brain
      irradiation for anaplastic astrocytoma.

PMID- 21720810
TI  - Preliminary use of differential scanning calorimetry of cerebrospinal fluid for
      the diagnosis of glioblastoma multiforme.
AB  - Thermal stability signatures of complex molecule interaction in biological fluids
      can be measured using a new approach called differential scanning calorimetry
      (DSC). The thermal stability of plasma proteome has been described previously as
      a method of producing a disease-specific "signature," termed thermogram, in
      several neoplastic and autoimmune diseases. We describe the preliminary use of
      DSC performed on cerebrospinal fluid (CSF) as a diagnostic tool for the
      identification of patients with glioblastoma multiforme (GBM). Samples of CSF
      from nine patients with confirmed GBM were evaluated using DSC, and the
      thermogram signatures evaluated. These thermograms were compared with thermograms
      of CSF taken from patients with non-neoplastic conditions such as head trauma,
      hydrocephalus, or CSF leak. Further analysis was also performed on CSF from
      patients who had non-GBM neoplastic conditions such as carcinomatosis meningitis
      or central nervous system lymphoma or leukemia. The DSC thermograms of CSF of the
      patients with GBM were significantly different when compared with other
      neoplastic and non-neoplastic cases. The melting temperature of the major
      transition was shifted by 5 degrees C, which makes it easily distinguishable from
      control cases. Our results are very preliminary, but it appears that the DSC of
      CSF has potential utility in diagnostics and monitoring disease progression in
      GBM patients.

PMID- 21720811
TI  - Changes in chemosensitivity and mechanosensitivity in aging and Parkinson's
      disease.
AB  - The risk of aspiration pneumonia in Parkinson's disease (PD) may be increased by
      sensory loss in the laryngopharynx and a reduced cough reflex. This study
      investigated changes in chemo- and mechanosensation with age and in PD and
      documented cough thresholds and cortical influences over cough. Single-breath
      citric acid inhalation cough challenge and flexible nasendoscopy were performed
      in 32 participants with idiopathic PD (mean age = 68.5 years, range = 45.8-82.5)
      and 16 healthy young adults (8 males, mean age = 25.1 years, range = 21.3-32.4),
      and 16 healthy elders (8 males, mean age = 72.8 years, range = 61.5-84.7) as
      controls. Individuals with PD had reduced sensation at the base of the tongue
      compared to age- and gender-matched counterparts (p < 0.005). All groups
      demonstrated lower natural cough thresholds than suppressed cough thresholds. No
      differences in natural cough thresholds were found across groups. Young adults
      demonstrated greater ability to suppress cough compared to healthy elders (p =
      0.021). Tongue-base mechanosensory impairment in PD may account for vallecular
      residue and complaints of globus sensation. However, decreased cough response was
      not found to be a characteristic of PD. This study provided evidence for
      voluntary control of cough and the lack of decline of chemosensitivity with age
      or disease.

PMID- 21720812
TI  - Stress response gene activation protects sea urchin embryos exposed to X-rays.
AB  - We used Paracentrotus lividus sea urchin embryos, a well-established model in
      developmental biology and ecotoxicology, for investigation on stress/anti
      apoptotic protein expression elicited in response to harmful ionizing radiation,
      such as X-rays. We evaluated the acute effects of a high-dose exposure (5 Gy) on
      P. lividus analyzing by Western blotting the accumulation levels of HSP60, HSP70,
      BAG3 and a putative p63 at 24 and 48 h after irradiation. We found an increase in
      the HSP70, BAG3, and p63 protein levels only 48 h after irradiation, whereas no
      HSP60 increase was detected either at 24 or 48 h. Levels of the mRNA coding for
      HSP70 and p63 were also investigated by relative RT-PCR and were found to
      increase 24 h after irradiation, returning to their initial levels at 48 h.
      Results demonstrate the presence of an adaptive regulatory mechanism operating at
      the transcriptional level at 24 h, followed by a translational activation at 48 h
      post-irradiation. In conclusion, our findings confirm the sea urchin embryo as a
      sensible bioindicator of cell damage and we propose this model for studies on the
      protective pathways activated in response to X-rays. The novel result of the
      involvement of BAG3 and p63 in the response to X-rays, never tested so far in any
      other embryonic system, opens the way for their use as biomarkers of X-ray
      hazards.

PMID- 21720813
TI  - Long-term results of therapy with mycophenolate mofetil in chronic non-infectious
      uveitis.
AB  - BACKGROUND: Short-term studies have shown mycophenolate mofetil (MMF) to be a
      useful immunosuppressive agent for the treatment of intraocular inflammation. The
      aim of our study was to assess the long-term efficacy and tolerability of MMF in
      patients with chronic non-infectious uveitis, as well as to analyze disease
      course following discontinuation of therapy. METHODS: This is a retrospective
      case series on 60 uveitis patients treated with MMF with a follow-up period of at
      least 5 years. The main outcome measures were: control of inflammation,
      corticosteroid-sparing potential, side-effects, ability to stop/taper MMF
      treatment because of effective control of inflammation and relapse rate after
      therapy discontinuation. RESULTS: Control of intraocular inflammation (efficacy
      of MMF), defined as inactive disease under prednisolone dose of <= 10 mg daily,
      was achieved in 43 of 60 patients (72%) after 1 year of MMF treatment at a rate
      of 0.72 per patient-year (PY), and in 45 of 55 patients (82%) after 2 years
      therapy (rate: 0.41/PY). An improvement (3 lines) or stabilization of visual
      acuity was observed in 49 patients (82%), and a worsening in 11 patients (18%,
      95% CI: 10-30%). The probability of discontinuing prednisolone, estimated by the
      Kaplan-Meier method, was 40% after 5 years therapy. The probability of
      discontinuing mycophenolate mofetil due to efficacy was 33% after 5 years
      treatment. Recurrences of uveitis occurred in six of 21 patients (29%, rate:
      0.11/PY) after MMF discontinuation due to efficacy. The treatment was stopped
      because of inefficacy in 12 patients (rate: 0.05/PY) and because of side-effects
      in four patients (rate: 0.02/PY). The rate of adverse effects during MMF therapy
      was 0.17/PY. CONCLUSIONS: Our data show that mycophenolate mofetil is generally
      effective and well tolerated in the treatment of chronic non-infectious uveitis.

PMID- 21720814
TI  - Confocal laser-scanning microscopy allows differentiation between Fabry disease
      and amiodarone-induced keratopathy.
AB  - BACKGROUND: The aim of this work is to compare the microstructure of cornea
      verticillata in Fabry disease with amiodarone-induced keratopathy by means of in
      vivo confocal laser-scanning microscopy (CLSM). METHODS: Ten eyes of ten patients
      suffering from Fabry disease, six eyes of six patients with amiodarone-induced
      keratopathy and eight eyes of healthy control subjects were examined by
      conventional slit-lamp microscopy and CLSM. One Fabry patient received amiodarone
      therapy. All Fabry patients were under enzyme replacement therapy with agalsidase
      alfa. RESULTS: Seven out of ten Fabry patients and all patients receiving
      amiodarone showed typical cornea verticillata on slit-lamp examination. CLSM
      revealed hyper-reflective intracellular inclusions in basal epithelial cells of
      all Fabry patients with cornea verticillata and in one Fabry patient without slit
      lamp-detectable vortex keratopathy, as well as in all eyes featuring amiodarone
      keratopathy. Amiodarone deposits were more reflective and of grossly different
      size. Seven Fabry patients and all amiodarone patients had stromal microdots. Two
      amiodarone patients showed amiodarone inclusions in the endothelium. The number
      of CLSM changes in Fabry patients did not correlate with that of slit-lamp
      detectable cornea verticillata. CONCLUSIONS: While Fabry-induced cornea
      verticillata and amiodarone keratopathy cannot be distinguished by conventional
      slit-lamp microscopy, CLSM allows the differentiation between both etiologies in
      the majority of patients. CLSM appears to reveal corneal changes prior to the
      detection of cornea verticillata on slit-lamp microscopy and may thus be helpful
      in the early diagnosis of Fabry disease. CLSM does not allow quantitative
      monitoring of corneal changes in Fabry patients under enzyme-replacement therapy.

PMID- 21720815
TI  - Transitioning from stratus OCT to cirrus OCT: a comparison and a proposed
      equation to convert central subfield macular thickness measurements in healthy
      subjects.
AB  - BACKGROUND: The purpose of this paper is to study the differences between central
      subfield macular thickness (CSMT) measurements obtained by time-domain Stratus
      optical coherence tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss
      Meditec, Dublin, CA) and to formulate an equation to convert CSMT values from one
      to the other. METHODS: CSMT were measured by both Stratus Macula OCT and Cirrus
      Macula OCT in 46 healthy subjects. Agreement between measurements was calculated
      using Lin's concordance coefficient. RESULTS: The average age of our group was 30
      with the logMAR visual acuity of -0.015. The Stratus CSMT measurement (mean +/-
      standard deviation) 193.91 +/- 21.7 was statistically significant from the Cirrus
      CSMT measurement 252.82 +/- 28.4 (p < 0.001). The transformation equation 0.76*
      0.51 from Cirrus to Stratus resulted in values that best agreed with the observed
      Stratus OCT values. CONCLUSIONS: We identified a significant difference of CSMT
      measurements between Stratus and Cirrus. The Cirrus typically gave a higher value
      of CSMT. We derived a linear equation to convert the measurements from Cirrus to
      Stratus which resulted in transformed values that concord with the observed
      Stratus OCT values.

PMID- 21720816
TI  - Invisible scar endoscopic thyroid surgery by the dorsal approach: importance of
      the spinal accessory nerve.
AB  - PURPOSE: With about 100,000 surgeries per year in Germany, thyroid operations
      count among the most common procedures performed in general and endocrine
      visceral surgery. Twentieth century technological development gives the
      opportunity to perform thyroid surgery without leaving visible scar like
      conventional approaches do. This study is part of the work on the videoendoscopic
      retro-auricular access to the thyroid gland using the EndoCATS method by Schardey
      and Schopf. To avoid possible complications with the spinal accessory nerve
      (SAN), like irritation or injury of the nerve as happened during a feasibility
      study, a systematic study of the surgical anatomy at the nerve's entry to the
      posterior cervical triangle is performed especially in relation to the EndoCATS
      operation method. METHODS: Sixty-one neck regions in fifty-three specimens were
      examined at the anatomical institute of Munich to investigate the course of the
      SAN relative to the anatomic landmarks tip of mastoid bone, sternal notch, and
      posterior border of the sternocleidomastoid muscle together with the SAN's course
      variants at its entry to the posterior cervical triangle. The results were then
      statistically analyzed. RESULTS: From this analysis, we derived a simple method
      to predict the course of the SAN preoperatively and offer a new approach to
      protect the SAN during EndoCATS surgery. Additionally, we found a significant
      difference of the SAN's course between male and female specimens. CONCLUSION: The
      EndoCATS method can be a safe alternative to conventional thyroid surgery, but
      the SAN is at risk during the surgery procedure. Here we give feasible solutions
      to eliminate the SAN-problem performing EndoCATS thyroid surgery.

PMID- 21720817
TI  - Epidemiology of stress urinary incontinence in women.
AB  - Stress urinary incontinence is common and affects many women globally. About 50%
      of women with urinary incontinence report symptoms of stress incontinence, but
      estimates of the prevalence and incidence are limited by inconsistent methods of
      measurement between epidemiologic studies in different populations. Estimates
      also are affected by underlying differences in the age and ethnicity of study
      populations. Longitudinal studies assessing the incidence and natural history of
      stress incontinence estimate an annual incidence of 4% to 10%. While remission
      does occur, data on this remains sparse. Multiple risk factors have been
      associated with stress incontinence and may to contribute to the development of
      the condition. Recent epidemiologic studies have focused on defining additional
      lower urinary tract symptoms besides mixed or urge incontinence that may be
      associated with stress incontinence, but the significance of this is not yet
      known.

PMID- 21720818
TI  - Effects of nerve growth factor in experimental model of focal microgyria.
AB  - AIM: The effects on neural repair of intraparenchymal nerve growth factor (NGF)
      administration were evaluated in neonate Wistar rats with experimentally induced
      focal microgyria. METHODS: A freezing focal polymicrogyric lesion was induced on
      the frontal cortex in 35 newborn Wistar rats on postnatal day 1. NGF was
      administered in 15 cases, with 20 pups as controls. Animals were sacrificed at 72
      h and 7 days after NGF administration. Real-time PCR was used for the
      quantification of the expression of TrkA, p75, and doublecortin (DCX) at the
      level of the cortical lesion in seven different groups of animals: control 72 h
      (n = 5), control 7 days (n = 5), microgyria 72 h (n = 5), microgyria 7 days (n =
      5), microgyria + NGF 72 h (n = 5), microgyria + NGF 7 days (n = 5), and control +
      NGF (n = 5). RESULTS: A significant increase in TrkA expression was found in the
      microgyria + NGF 7 days group compared to the others. TrkA upregulation was
      already visible 72 h after NGF administration. Unlike TrkA, p75 expression
      increased in animals subjected to the experimental focal microgyria and decreased
      markedly after NGF administration. DCX expression in injured animals was observed
      to increase strongly 7 days after NGF administration compared with other groups.
      CONCLUSIONS: NGF administration interferes with neural repair mechanisms at the
      polymicrogyric lesion site by means of TrkA and DCX upregulation which possibly
      counteracts the process of apoptosis caused by the brain injury.

PMID- 21720819
TI  - Correlations between the abnormal development of the skull base and facial
      skeleton growth in anterior synostotic plagiocephaly: the predictive value of a
      classification based on CT scan examination.
AB  - BACKGROUND: Anterior cranial plagiocephaly, depending on the early hemicoronal
      suture fusion, is the most relevant form of plagiocephaly in terms of clinical
      implications. Its estimated incidence ranges between 0.4 and 1 per 1,000 live
      births. In the present report, we aim at validating the classification of Di
      Rocco and Velardi, proposing a scheme based on basicranium analysis using CT
      scans and its predictive value by evaluating the developmental characteristics of
      a population of adult subjects affected by anterior plagiocephaly who had
      underwent the surgical correction in the first months of life. MATERIALS AND
      METHODS: The group of patients here considered was retrieved from among all
      patients operated upon for craniostenosis in the pediatric neurosurgery unit of
      Policlinico Gemelli in Rome between January 1, 1980 and December 31, 1989. The
      study group consisted of 13 patients, seven females and six males, affected by
      anterior synostotic plagiocephaly ranging in age between 20 and 32 years (mean
      25.54 years). We also formed a group of unaffected patients in order to control
      for normal variability in the population. The subjects of the study group were
      evaluated using CT scan exams and cephalometric analyses were performed using
      three-dimensional reconstruction. DISCUSSION AND CONCLUSION: In this study, we
      were able to associate a facial phenotype to confirm the predictive value of the
      classification proposed. It is highly probable that the different outcomes depend
      on the different degrees of involvement in the synostotic process by the various
      skull base sutures which were essentially unaffected by the surgical procedures.

PMID- 21720820
TI  - Functional characterization of Class II 5-enopyruvylshikimate-3-phosphate
      synthase from Halothermothrix orenii H168 in Escherichia coli and transgenic
      Arabidopsis.
AB  - Although a large number of AroA enzymes (5-enopyruvylshikimate-3-phosphate
      synthase [EPSPS]) have been identified, cloned and tested for glyphosate
      resistance, only AroA variants derived from Agrobacterium tumefaciens strain CP4
      have been successfully used commercially. We have now used a polymerase chain
      reaction (PCR)-based two-step DNA synthesis (PTDS) method to synthesize an aroA
      gene (aroA(H. orenii)) from Halothermothrix orenii H168 encoding a new EPSPS
      similar to AroA(A. tumefaciens CP4.) AroA(H. orenii) was then expressed in
      Escherichia coli and key kinetic values of the purified enzyme were determined.
      Kinetic analysis of AroA(H. orenii) indicated that the full-length enzyme
      exhibited increased tolerance to glyphosate compared with E. coli AroA(E. coli)
      while retaining a high affinity for the substrate phosphoenolpyruvate. Transgenic
      Arabidopsis plants containing aroA(H. orenii) were resistant to 15 mM glyphosate.
      Site-directed mutagenesis showed that residues Thr355Ser affected the affinity of
      AroA(H. orenii) for glyphosate, providing further evidence that specific amino
      acid residues are responsible for differences in enzymatic behavior among
      different AroA enzymes.

PMID- 21720821
TI  - LC-PUFA from photosynthetic microalgae: occurrence, biosynthesis, and prospects
      in biotechnology.
AB  - Microalgae offer potential for numerous commercial applications, among them the
      production of long-chain polyunsaturated fatty acids (LC-PUFAs). These valuable
      fatty acids are important for a variety of nutraceutical and pharmaceutical
      purposes, and the market for these products is continually growing. An
      appropriate ratio of LC-PUFA of the omega-3 and omega-6 groups is vital for
      "healthy" nutrition, and adequate dietary intake has strong health benefits in
      humans. Microalgae of diverse classes are primary natural producers of LC-PUFA.
      This mini-review presents an introductory overview of LC-PUFA-related health
      benefits in humans, describes LC-PUFA occurrence in diverse microalgal classes,
      depicts the major pathways of their biosynthesis in microalgae, and discusses the
      prospects for microalgal LC-PUFA production.

PMID- 21720822
TI  - Identification of a new subfamily of salt-tolerant esterases from a metagenomic
      library of tidal flat sediment.
AB  - To search for novel lipolytic enzymes, a metagenomic library was constructed from
      the tidal flat sediment of Ganghwa Island in South Korea. By functional screening
      using tributyrin agar plates, 3 clones were selected from among the 80,050 clones
      of the fosmid library. The sequence analysis revealed that those clones contained
      different open reading frames, which showed 50-57% amino acid identity with
      putative lipolytic enzymes in the database. Based on the phylogenetic analysis,
      they were identified to encode novel members, which form a distinct and new
      subfamily in the family IV of bacterial lipolytic enzymes. The consensus
      sequence, GT(S)SA(G)G, encompassing the active site serine of the enzymes was
      different from the GDSAG motif, conserved in the other subfamily. The genes were
      expressed in Escherichia coli and recombinant proteins were purified as active
      soluble forms. The enzymes showed the highest activity toward p-nitrophenyl
      valerate (C5) and exhibited optimum activities at mesophilic temperature ranges
      and slightly alkaline pH. In particular, the enzymes displayed salt tolerance
      with over 50% of the maximum activity remained in the presence of 3 M NaCl (or
      KCl). In this study, we demonstrated that the metagenomic approach using marine
      tidal flat sediment as a DNA source expanded the diversity of lipolytic enzyme
      encoding genes.

PMID- 21720823
TI  - Effect of alternative NAD+-regenerating pathways on the formation of primary and
      secondary aroma compounds in a Saccharomyces cerevisiae glycerol-defective
      mutant.
AB  - Saccharomyces cerevisiae maintains a redox balance under fermentative growth
      conditions by re-oxidizing NADH formed during glycolysis through ethanol
      formation. Excess NADH stimulates the synthesis of mainly glycerol, but also of
      other compounds. Here, we investigated the production of primary and secondary
      metabolites in S. cerevisiae strains where the glycerol production pathway was
      inactivated through deletion of the two glycerol-3-phosphate dehydrogenases genes
      (GPD1/GPD2) and replaced with alternative NAD(+)-generating pathways. While these
      modifications decreased fermentative ability compared to the wild-type strain,
      all improved growth and/or fermentative ability of the gpd1Deltagpd2Delta strain
      in self-generated anaerobic high sugar medium. The partial NAD(+) regeneration
      ability of the mutants resulted in significant amounts of alternative products,
      but at lower yields than glycerol. Compared to the wild-type strain, pyruvate
      production increased in most genetically manipulated strains, whereas acetate and
      succinate production decreased in all strains. Malate production was similar in
      all strains. Isobutanol production increased substantially in all genetically
      manipulated strains compared to the wild-type strain, whereas only mutant strains
      expressing the sorbitol producing SOR1 and srlD genes showed increases in isoamyl
      alcohol and 2-phenyl alcohol. A marked reduction in ethyl acetate concentration
      was observed in the genetically manipulated strains, while isobutyric acid
      increased. The synthesis of some primary and secondary metabolites appears more
      readily influenced by the NAD(+)/NADH availability. The data provide an initial
      assessment of the impact of redox balance on the production of primary and
      secondary metabolites which play an essential role in the flavour and aroma
      character of beverages.

PMID- 21720824
TI  - Post-mortem volatiles of vertebrate tissue.
AB  - Volatile emission during vertebrate decay is a complex process that is understood
      incompletely. It depends on many factors. The main factor is the metabolism of
      the microbial species present inside and on the vertebrate. In this review, we
      combine the results from studies on volatile organic compounds (VOCs) detected
      during this decay process and those on the biochemical formation of VOCs in order
      to improve our understanding of the decay process. Micro-organisms are the main
      producers of VOCs, which are by- or end-products of microbial metabolism. Many
      microbes are already present inside and on a vertebrate, and these can initiate
      microbial decay. In addition, micro-organisms from the environment colonize the
      cadaver. The composition of microbial communities is complex, and communities of
      different species interact with each other in succession. In comparison to the
      complexity of the decay process, the resulting volatile pattern does show some
      consistency. Therefore, the possibility of an existence of a time-dependent core
      volatile pattern, which could be used for applications in areas such as forensics
      or food science, is discussed. Possible microbial interactions that might alter
      the process of decay are highlighted.

PMID- 21720825
TI  - Listeria bacteriophage peptidoglycan hydrolases feature high thermoresistance and
      reveal increased activity after divalent metal cation substitution.
AB  - The ability of the bacteriophage-encoded peptidoglycan hydrolases (endolysins) to
      destroy Gram-positive bacteria from without makes these enzymes promising
      antimicrobials. Recombinant endolysins from Listeria monocytogenes phages have
      been shown to rapidly lyse and kill the pathogen in all environments. To
      determine optimum conditions regarding application of recombinant Listeria phage
      endolysins in food or production equipments, properties of different Listeria
      endolysins were studied. Optimum NaCl concentration for the amidase HPL511 was
      200 nM and 300 mM for the peptidases HPL118, HPL500, and HPLP35. Unlike most
      other peptidoglycan hydrolases, all four enzymes exhibited highest activity at
      elevated pH values at around pH 8-9. Lytic activity was abolished by EDTA and
      could be restored by supplementation with various divalent metal cations,
      indicating their role in catalytic function. While substitution of the native
      Zn(2+) by Ca(2+) or Mn(2+) was most effective in case of HPL118, HPL500, and
      HPLP35, supplementation with Co(2+) and Mn(2+) resulted in an approximately 5
      fold increase in HPL511 activity. Interestingly, the glutamate peptidases feature
      a conserved SxHxxGxAxD zinc-binding motif, which is not present in the amidases,
      although they also require centrally located divalent metals for activity. The
      endolysins HPL118, HPL511, and HPLP35 revealed a surprisingly high
      thermostability, with up to 35% activity remaining after 30 min incubation at 90
      degrees C. The available data suggest that denaturation at elevated temperatures
      is reversible and may be followed by rapid refolding into a functional state.

PMID- 21720826
TI  - Health-specific optimism mediates between objective and perceived physical
      functioning in older adults.
AB  - Particularly in older adults, self-reports of physical health need not
      necessarily reflect their objective health status as they can be biased by
      optimism. In this study, we examine whether the effect of objective physical
      functioning on subjective physical functioning is modified by health-specific
      optimism and self-efficacy. A longitudinal study with three measurement points
      over 6 months and 309 older adults (aged 65-85) with multimorbidity was
      conducted. Subjective physical functioning was regressed on objective physical
      functioning, health-specific optimism and self-efficacy. Subjective physical
      functioning was predicted by both objective physical functioning and optimism as
      a mediator. Moreover, an interaction between optimism and self-efficacy was
      found: Optimism predicted subjective physical functioning only for individuals
      with low self-efficacy. Subjective physical functioning is as much based on
      objective physical functioning as it is on health-specific optimism. Older adults
      base their subjective physical functioning on objective indicators but also on
      optimism, when they are less self-efficacious.

PMID- 21720827
TI  - Beyond conventional socioeconomic status: examining subjective and objective
      social status with self-reported health among Asian immigrants.
AB  - Despite mounting evidence for a strong and persistent association between
      socioeconomic status (SES) and health, this relationship is largely unknown among
      Asian immigrants, a fast growing minority group in the US population. Previous
      research has typically focused on objective SES (primarily education and income)
      and ignored self-perceived SES. Using data from the National Latino and Asian
      American Study (NLAAS) (N = 1,570), we examined the impact of subjective as well
      as objective SES upon multiple self-reported health outcomes among Asian
      immigrants. Results indicated that conventional SES indicators by and large were
      non-significantly related to self-rated physical health, physical discomfort,
      self-rated mental health, and psychological distress. In contrast, subjective SES
      relative to people in the United States and people in the community showed strong
      associations with health outcomes above and beyond conventional SES markers. This
      study suggested a promising avenue to incorporate subjective SES in health
      disparities research, especially among immigrants.

PMID- 21720828
TI  - Distinct modes of vertebrate hypaxial muscle formation contribute to the teleost
      body wall musculature.
AB  - The formation of the body wall musculature in vertebrates is assumed to be
      initiated by direct ventral extension of the somites/myotomes. This contrasts to
      the formation of limb muscles and muscles involved in feeding or
      respiration/ventilation, which are founded by migratory muscle precursors (MMPs)
      distant to the somites. Here, we present evidence from morphology and expression
      of molecular markers proposing that the formation of the two muscle layers of the
      teleost body wall involves both of the above mechanisms: (1) MMPs from somites 5
      and 6 found an independent muscle primordium-the so-called posterior hypaxial
      muscle (PHM)-which subsequently gives rise to the most anterior two segments of
      the medial obliquus inferioris (OI) muscle. (2) Direct epithelial extension of
      the hypaxial myotomes generates the OI segments from somite 7 caudalward and the
      entire lateral obliquus superioris (OS) muscle. The findings are discussed in
      relation to the evolution of hypaxial myogenic patterning including functional
      considerations. We hypothesise that the potential of the most anterior somites to
      generate migratory muscle precursors is a general vertebrate feature that has
      been differently utilised in the evolution in vertebrate groups.

PMID- 21720829
TI  - Molecular response of the bloom-forming cyanobacterium, Microcystis aeruginosa,
      to phosphorus limitation.
AB  - Cyanobacteria blooms caused by species such as Microcystis have become
      commonplace in many freshwater ecosystems. Although phosphorus (P) typically
      limits the growth of freshwater phytoplankton populations, little is known
      regarding the molecular response of Microcystis to variation in P concentrations
      and sources. For this study, we examined genes involved in P acquisition in
      Microcystis including two high-affinity phosphate-binding proteins (pstS and
      sphX) and a putative alkaline phosphatase (phoX). Sequence analyses among ten
      clones of Microcystis aeruginosa and one clone of Microcystis wesenbergii
      indicates that these genes are present and conserved within the species, but
      perhaps not the genus, as phoX was not identified in M. wesenbergii. Experiments
      with clones of M. aeruginosa indicated that expression of these three genes was
      strongly upregulated (50- to 400-fold) under low inorganic P conditions and that
      the expression of phoX was correlated with alkaline phosphatase activity (p <
      0.005). In contrast, cultures grown exclusively on high levels of organic
      phosphorus sources (adenosine 5'-monophosphate, beta-glycerol phosphate, and D: 
      glucose-6-phosphate) or under nitrogen-limited conditions displayed neither high
      levels of gene expression nor alkaline phosphatase activity. Since Microcystis
      dominates phytoplankton assemblages in summer when levels of inorganic P (P(i))
      are often low and/or dominate lakes with low P(i) and high organic P, our
      findings suggest this cyanobacterium may rely on pstS, sphX, and phoX to
      efficiently transport P(i) and exploit organic sources of P to form blooms.

PMID- 21720830
TI  - [Acting in concert: comments on the article by M. Schmedders et al on different
      therapy approaches for prostate cancer with low risks].

PMID- 21720831
TI  - [Overweight is an advantageous prognostic marker in patients with clear cell
      kidney cancer].
AB  - OBJECTIVES: Obesity increases the risk of developing renal cell carcinoma (RCC).
      We assessed whether different body mass index (BMI) levels and the body surface
      area (BSA) at the time of surgery had an effect on aggressiveness and long-term
      prognosis of RCC. METHODS: The study included 1,595 RCC patients with complete
      information about their BMI who had undergone surgery for renal cell cancer at
      the University Hospitals in Hannover (MHH) and Marburg between 1990 and 2005. The
      mean follow-up was 5.0 years. RESULTS: A higher BMI and a higher than average BSA
      were significantly associated with younger age. A high BMI value was additionally
      related to a lower tumor grade, the clear cell histological subtype, and
      metastasis at the time of diagnosis. Overweight patients had a significantly
      lower risk of cancer-related death; their median 5-year tumor-specific survival
      rate was 76.9% (BMI>30) and 72.6% (BMI 25-30) as opposed to 63.5% for patients
      with a BMI below 25 (p<0.001). However, the positive correlation between a high
      BMI and tumor-specific survival could be confirmed in multivariable analyses for
      localized clear cell RCC only. CONCLUSION: We identified BMI as an independent
      prognostic marker of improved cancer-specific survival in patients with RCC,
      particularly with organ-confined clear cell cancer.

PMID- 21720832
TI  - Different bladder defects reconstructed with bladder acellular matrix grafts in a
      rabbit model.
AB  - OBJECTIVE: To evaluate the potential use of the bladder acellular matrix graft
      (BAMG), two different bladder defects in the rabbit model were reconstructed.
      MATERIALS AND METHODS: Two groups of rabbits underwent partial bladder wall
      cystectomy (group A, 30-40%; group B, 70-60%) and reconstruction of the defects
      with an equally sized BAMG. After 4, 12, and 24 weeks, bladder cystographs were
      performed. Then the rabbits were killed after uneventful postoperative periods,
      and the grafts were harvested for H&E staining and immunohistochemical staining.
      RESULTS: Two rabbits died on the postoperative days 3 and 6 in group A due to
      urinary peritonitis. At 24 weeks, in group A, the reconstructed bladders reached
      a mean volume of 94.39+/-0.54% of the precystectomy bladder capacity.
      Histologically, complete regeneration of smooth muscle and urothelium tissue was
      evident. Regenerated SMCs and urothelium stained positive for alpha-smooth muscle
      actin and AE1/AE3. In group B, the mean bladder volume was 64.5+/-3.19% of the
      precystectomy volume. Histologically, group B was characterized by multilayered
      urothelium without organized muscle tissue. CONCLUSION: The BAMG was an effective
      scaffold for bladder wall regeneration in the rabbit model. However, the use of
      BAMG reconstruction in larger bladder defects did not induce the same quality and
      quantity of bladder regeneration as the reconstruction of smaller bladder
      defects.

PMID- 21720833
TI  - [Information needs of patients with prostate cancer. Pronounced differences
      between individuals after diagnosis of localised prostate carcinoma].
AB  - BACKGROUND: In the context of shared decision-making it is important to know more
      about information needs of prostate cancer patients. Therefore, this study
      investigates content and extent of these information needs. MATERIAL AND METHODS:
      We surveyed 330 patients of 4 urological Clinics in Switzerland with a well
      established written questionnaire between 3 and 24 months after their diagnosis
      of an early-stage prostate cancer. A total of 179 patients responded and 128
      (39%) questionnaires were entered into final statistical analysis. RESULTS:
      Patients expressed broad information needs and pronounced differences between
      individuals were observed. Each of the 92 questions presented was rated as
      "essential" by at least 18% of the patients. On average 50 questions were rated
      as 'essential'. One patient rated only four questions as 'essential' whereas
      another participant reported all 92 questions as being 'essential' to him.
      CONCLUSIONS: Concerning patient education it is important to identify the
      individual information needs of each prostate cancer patient separately.

PMID- 21720834
TI  - [Gaining insight--visualization of the invisible in urology: on the history of
      the technique and evidence in urological endoscopy].
AB  - The tactile inspection of the bladder had a long tradition in urology.
      Examination results and their interpretation depended heavily on the individual
      tactile skills of the urologist. Because this examination method (if correctly
      applied) proved the artistic skills and experience of a doctor, urologists did
      not see any need to replace tactile examinations with a competing
      method.Nevertheless, urology as well as many other medical disciplines was
      receptive to techniques aiming at the visualization of pathology. Visualizations
      served the purposes of science-oriented medicine to be objective and to document
      examination results. However, it needed the development of specific technologies
      to create objective images. One major problem in urology was the question of how
      to light body cavities. After extracorporeal light sources had proven to be
      ineffective, attempts were made at bringing light sources into the interior of
      the body. It needed heated tungsten filaments and later mignon bulbs at the tip
      of endoscopes to illuminate the bladder to such an extent that images from the
      interior of the bladder could be produced. The paper examines the status of these
      images as self-evident and objective. It is argued that the images produced were
      not self-evident. It is shown how combinations of texts and images were needed to
      develop an endoscopic viewing technique in order to read endoscopic images
      properly and to recognize those aspects of endoscopic documentations which were
      necessary for correct interpretations of the images.

PMID- 21720835
TI  - [Complications of radical retropubic prostatectomies based on the Martin
      criteria].
AB  - BACKGROUND: In 2002 the ten Martin criteria were proposed which should be met
      when reporting complications following surgery. Only a few studies have evaluated
      complication rates after open retropubic radical prostatectomy using these
      criteria. In this study we report on complications of open retropubic radical
      prostatectomy using the standardized Clavien-Dindo reporting methodology.
      PATIENTS AND METHODS: The overall complication rate was 28.6% (907 of 3,172). We
      registered 1,069 medical or surgical complications in 907 patients. Of these, 714
      complications were grade I (66.8%), 195 grade II (18.2%), 139 grade III (13%),
      and 17 grade IV (1.6%), respectively. The mortality rate (grade V) was 0.1% (4 of
      3,172). Older age (hazard ratio 1.049, p=0.023) and a performed lymphadenectomy
      (hazard ratio 1.804, p=0.024) were independent predictors for high-grade
      complications (grade III or greater) on multivariate analysis. RESULTS: Between
      08/2003 and 06/2010 complications of 3172 consecutive men who underwent open
      retropubic radical prostatectomy at a single center were recorded prospectively.
      Complications which occurred within a period of 30 days postoperatively were
      graded retrospectively according to the Clavien-Dindo classification. Clinical
      and histopathological risk factors were statistically evaluated for an
      association with complication grades. All 10 Martin criteria were fulfilled.
      CONCLUSIONS: Using the Clavien-Dindo classification as a standardized reporting
      methodology, we observed an acceptable overall complication rate of 28.6%. In the
      majority (85% of all complications) lower grade complications occurred. In this
      series older age and a lymphadenectomy were risk factors for high-grade
      complications (III-V). A patient's age remains an important factor when
      considering the indication for radical prostatectomy.

PMID- 21720836
TI  - [Benefit assessment by the Federal Joint Committee: assessment of treatment
      strategies for low risk prostate cancer].
AB  - One of the Federal Joint Committee's duties is to assess benefit, need, and cost
      effectiveness of diagnostic and therapeutic approaches. The aim is to decide
      whether they can be provided within the statutory health care system in Germany.
      The systematic assessment concerning low dose rate brachytherapy with permanent
      seed implantation for treatment of men with localized prostate cancer revealed
      that sufficient scientific evidence for its benefit compared to therapeutic
      alternatives is still missing. In 2009, the Federal Joint Committee recommended a
      randomized controlled trial in order to evaluate the different therapies. Based
      on a concept developed by the National Association of Statutory Health Insurance
      Funds urology and radiooncology experts and other protagonists are currently
      working on the steps to be taken for implementation of a preference-based
      randomized controlled trial to compare radical prostatectomy, percutaneous
      radiotherapy, low dose rate brachytherapy with permanent seed implantation, and
      active surveillance in the treatment of low or early intermediate risk prostate
      cancer.

PMID- 21720837
TI  - Dissolution and delignification of bamboo biomass using amino acid-based ionic
      liquid.
AB  - In the present work, the dissolution of bamboo biomass was tested using a number
      of ionic liquids synthesized in laboratory. It was observed that one of the
      synthesized amino acid-based ionic liquids, namely 1-ethyl-3-methylimidazolium
      glycinate, was capable of dissolving the biomass completely. The dissolved
      biomass was then regenerated using a reconstitute solvent (acetone/water) and was
      characterized using Fourier transform infrared spectroscopy, X-ray diffraction,
      and scanning electron microscopy. The results were compared to preconditioned
      bamboo biomass. The regenerated biomass was found to have a more homogenous
      macrostructure, which indicates that the crystalline form and structure of its
      cellulose has changed from type Iota to type IotaIota during the dissolution and
      regeneration process.

PMID- 21720838
TI  - Isolation, identification, and culture optimization of a novel glycinonitrile
      hydrolyzing fungus-Fusarium oxysporum H3.
AB  - Microbial transformation of glycinonitrile into glycine by nitrile hydrolase is
      of considerable interest to green chemistry. A novel fungus with high nitrile
      hydrolase was newly isolated from soil samples and identified as Fusarium
      oxysporum H3 through 18S ribosomal DNA, 28S ribosomal DNA, and the internal
      transcribed spacer sequence analysis, together with morphology characteristics.
      After primary optimization of culture conditions including pH, temperature,
      carbon/nitrogen sources, inducers, and metal ions, the enzyme activity was
      greatly increased from 326 to 4,313 U/L. The preferred carbon/nitrogen sources,
      inducer, and metal ions were glucose and yeast extract, caprolactam, and Cu(2+),
      Mn(2+), and Fe(2+), respectively. The maximum enzyme formation was obtained when
      F. oxysporum H3 was cultivated at 30  degrees C for 54 h with the initial pH of
      7.2. There is scanty report about the optimization of nitrile hydrolase
      production from nitrile-converting fungus.

PMID- 21720839
TI  - Co-expression of an organic solvent-tolerant lipase and its cognate foldase of
      Pseudomonas aeruginosa CS-2 and the application of the immobilized recombinant
      lipase.
AB  - The genes of CS-2 lipase and its cognate foldase were cloned from Pseudomonas
      aeruginosa CS-2. A stop codon was not found in the lipase gene. The amino acid
      sequence deduced from the lipase gene from P. aeruginosa CS-2 showed 97.8%,
      71.3%, and 71.2% identity with lipases from P. aeruginosa LST-03, P seudomonas
      mendocina ymp, and Pseudomonas stutzeri A1501, respectively. The co-expression of
      CS-2 lipase and its cognate foldase of P. aeruginosa CS-2 in E scherichia coli
      BL21 (DE3) resulted in the formation of a soluble lipase. The recombinant lipase
      and foldase were purified to homogeneity using nickel affinity chromatography and
      about 10.2-fold with 40.9% recovery was achieved for the purification of the
      recombinant lipase. The molecular masses of the lipase and the foldase were
      estimated to be 35.7 and 38.3 kDa in SDS-PAGE, respectively. The recombinant
      lipase showed stability in the presence of some organic solvents. The recombinant
      CS-2 lipase was immobilized and subsequently used for the synthesis of butyl
      acetate in heptane. The conversion of substrate decreased from 98.2% to 87.4%
      after 5 cycles in reuse of the immobilized lipase.

PMID- 21720840
TI  - [Ulceration on the bridge of the nose in a young adult].
AB  - Nasal dermoid sinus represents an entity of embryonic malformation of the
      midface. The diagnostic approach includes computed tomography for assessment of
      the bony components and magnetic resonance imaging for assessment of the soft
      tissue structures and potential intracranial involvement. Both techniques are
      essential for the imperative surgical treatment.

PMID- 21720841
TI  - [State-dependent motivational interviewing for people with schizophrenia and
      substance use: results of a randomised controlled trial].
AB  - BACKGROUND: Comorbid substance use disorder in patients with schizophrenia is
      associated with poor clinical and social outcome and low compliance with
      integrated outpatient treatment programs. For the first time the present trial
      compares the efficacy of four sessions of motivational interviewing (MI) and four
      sessions of supportive therapy (ST). The primary outcome was compliance with
      integrated outpatient treatment post-intervention. Secondary outcomes were
      substance use, psychopathology, compliance with medication and stage of change in
      psychotherapy. METHODS: Sixty inpatients with schizophrenia and substance use
      disorder were randomised to receive either four sessions of MI or four sessions
      of ST. Masked assessments took place at baseline, post-treatment and 3- and 6
      month follow-ups. RESULTS: The integrated outpatient program was attended by
      70.0% of the MI (n=30) and 40.0% of the ST patients (n=30; p=0.020). There were
      no differences regarding secondary outcome between MI and ST groups. CONCLUSION:
      The study design allows one for the first time to attribute the findings to the
      specific effects of MI and thereby emphasizes the effectiveness of this
      particular treatment approach. In summary, these findings show that the
      integration of short-term MI for people with both psychosis and substance abuse
      could significantly improve their chances of attending appropriate outpatient
      settings and thereby improve their well-being.

PMID- 21720842
TI  - Aortic pressure wave reconstruction during exercise is improved by adaptive
      filtering: a pilot study.
AB  - Reconstruction of central aortic pressure from a peripheral measurement by a
      generalized transfer function (genTF) works well at rest and mild exercise at
      lower heart rates, but becomes less accurate during heavy exercise. Particularly,
      systolic and pulse pressure estimations deteriorate, thereby underestimating
      central pressure. We tested individualization of the TF (indTF) by adapting its
      resonance frequency at the various levels of exercise. In seven males (age 44-57)
      with coronary artery disease, central and peripheral pressures were measured
      simultaneously. The optimal resonance frequency was predicted from regression
      formulas using variables derived from the individual's peripheral pressure pulse,
      including a pulse contour estimation of cardiac output (pcCO). In addition,
      reconstructed pressures were calibrated to central mean and diastolic pressure at
      each exercise level. Using a genTF and without calibration, the error in
      estimated aortic pulse pressure was -7.5 +/- 6.4 mmHg, which was reduced to 0.2
      +/- 5.7 mmHg with the indTFs using pcCO for prediction. Calibration resulted in
      less scatter at the cost of a small bias (2.7 mmHg). In exercise, the indTFs
      predict systolic and pulse pressure better than the genTF. This pilot study shows
      that it is possible to individualize the peripheral to aortic pressure transfer
      function, thereby improving accuracy in central blood pressure assessment during
      exercise.

PMID- 21720843
TI  - Hyalinizing trabecular tumor of the thyroid: a case report.
AB  - Hyalinizing trabecular tumor (HTT) of the thyroid is a rare neoplasm that was
      first described by Carney in 1987. It is a tumor of follicular derivation with
      peculiar nuclear, architectural, histochemical, and immunohistochemical features.
      We report a case of HTT in a 69-year-old woman with a mutinodular goiter. Since
      the clinical and ultrasonographic features were nonspecific, fine needle
      aspiration biopsy (FNAB) of the left lobe-dominant node was performed that
      resulted in an indeterminate cytologic diagnosis (category THY-3). The patient
      underwent total thyroidectomy, with a histologic diagnosis of HTT. We discuss the
      clinical and diagnostic approach, including the role of FNAB, and the pathologic
      features of HTT with special reference to the possible differential diagnosis.
      Total thyroidectomy or hemithyroidectomy represent adequate treatments, while
      radioiodine ablation is not standard. Although rare cases of malignant HTT have
      been documented, this tumor should be considered a benign neoplasm or, at most, a
      neoplasm of extremely low malignant potential. As a consequence, once this
      diagnosis is rendered, clinical management should be conservative, which may
      include a precautionary annual follow-up in order to exclude the very rare
      possibility of recurrence, as exceptionally reported.

PMID- 21720844
TI  - Site-directed mutagenesis of aromatic residues in the carbohydrate-binding module
      of Bacillus endoglucanase EGA decreases enzyme thermostability.
AB  - The endoglucanase, EGA, from Bacillus sp. AC-1 comprises a glycosyl hydrolase
      family-9 catalytic module (CM9) and a family-3 carbohydrate-binding module
      (CBM3). Seven aromatic residues were subjected to site-directed mutagenesis in
      both CBM3 and EGA to investigate their roles in enzyme thermostability. The
      complexes generated by mixing CBMY527G, CBMW532A, or CBMF592G with CM9 each lost
      their activities after 15 min at 45 degrees C, while the wild-type complex
      retained >70% activity after 2 h. The mutants EGAY527G, EGAW532A, and EGAF592G
      showed little activity after 15 min at 60 degrees C, whereas EGA remained 70%
      active after 2 h. Thus the residues Tyr(527), Trp(532), and Phe(592) contribute
      not only to CBM3-mediated stability of CM9 but also to EGA thermostability
      suggesting that hydrophobic interaction between the two modules, independent of
      covalent linkages, is important for enzyme thermostability.

PMID- 21720845
TI  - Use of chemometrics in the selection of a Saccharomyces cerevisiae expression
      system for recombinant cyprosin B production.
AB  - Two multivariate statistical methods, factor analysis (FA) and hierarchical
      cluster analysis (HCA), were applied to experimental data set to evaluate their
      usefulness in selecting the adequate expression system and optimal growth
      parameters for recombinant cyprosin B production. Using FA, the large data set
      was reduced to two factors representing 73.4% of variability. Factor 1, with
      53.5% of variability, corresponds to recombinant cyprosin B expression and
      efficient secretion, while factor 2, accounting for 19.9% of variability,
      represents cell growth and physiological characteristics. FA and HCA allowed the
      establishment of correlations among different variables and the clusters obtained
      providing clear identification of the experimental parameters related to cyprosin
      B production, which results on more accurate scientific output and time saving
      when selection of an adequate expression system is concerned.

PMID- 21720846
TI  - Discovery and characterization of a xylose reductase from Zymomonas mobilis ZM4.
AB  - Formation of xylitol, a byproduct from xylose fermentation, is a major limiting
      factor in ethanol production from xylose in engineered Zymomonas strains, yet the
      postulated xylose reductase remains elusive. We report here the discovery of
      xylose reductase in Zymomonas mobilis and, for the first time, to associate the
      enzyme function with its gene. Besides xylose and xylulose, the enzyme was active
      towards benzaldehyde, furfural, 5-hydroxymethyl furfural, and acetaldehyde,
      exhibiting nearly 150-times higher affinity with benzaldehyde than xylose. The
      discovery of xylose reductase paves the way for further improvement of xylose
      fermentation in Z. mobilis. The enzyme may also be used to mitigate toxicity of
      furfural and other inhibitors from plant biomass.

PMID- 21720847
TI  - Killer phenotype of indigenous yeasts isolated from Argentinian wine cellars and
      their potential starter cultures for winemaking.
AB  - Of 31 yeasts, from different surfaces of two cellars from the northwest region of
      Argentina, 11 expressed killer activity against the sensitive strain
      Saccharomyces cerevisiae P351. Five of these killer yeasts were identified as S.
      cerevisiae by phenotypic tests and PCR-RFLP analysis. Two S. cerevisiae killer
      strains, Cf5 and Cf8, were selected based on their excellent kinetic and
      enological properties as potential autochthonous mixed starter cultures to be
      used during wine fermentation. They could dominate the natural microbiota in
      fermentation vats and keep the typical sensorial characteristics of the wine of
      this region.

PMID- 21720848
TI  - Production of epsilon-poly-L-lysine by Streptomyces sp. using resin-based, in
      situ product removal.
AB  - Resin-based, in situ product removal (ISPR) was used to increase production of
      epsilon-poly-L-lysine (PL) by Streptomyces sp. GIM8. D152 resin was selected over
      Amberlite IRC-50, Amberlite IRC-76 and Amberlite IR-120 to develop ISPR using
      adsorption capacity and desorption ratio as bases. The yield of PL in response to
      external PL was unaffected in shake-flask culture; however, the production of PL
      increased to 2.9 from 0.8 g l(-1) shake-flasks using ISPR. In a 5 l fermentor,
      23.4 g PL l(-1) was achieved compared to 3.76 g PL l(-1), in the controls by
      attaching two bags of D152 resin to the probes and baffles of the fermentor.

PMID- 21720849
TI  - Neuropathology underlying clinical variability in patients with
      synucleinopathies.
AB  - Abnormal aggregates of the synaptic protein, alpha-synuclein, are the dominant
      pathology in syndromes known as the synucleinopathies. The cellular aggregation
      of the protein occurs in three distinct types of inclusions in three main
      clinical syndromes. alpha-Synuclein deposits in neuronal Lewy bodies and Lewy
      neurites in idiopathic Parkinson's disease (PD) and dementia with Lewy bodies
      (DLB), as well as incidentally in a number of other conditions. In contrast,
      alpha-synuclein deposits largely in oligodendroglial cytoplasmic inclusions in
      multiple system atrophy (MSA). Lastly, alpha-synuclein also deposits in large
      axonal spheroids in a number of rarer neuroaxonal dystrophies. Disorders are
      usually defined by their most dominant pathology, but for the synucleinopathies,
      clinical heterogeneity within the main syndromes is well documented. MSA was
      originally viewed as three different clinical phenotypes due to different
      anatomical localization of the lesions. In PD, recent meta-analyses have
      identified four main clinical phenotypes, and clinicopathological correlations
      suggest that more severe and more rapid progression of pathology with
      chronological age, as well as the involvement of additional neuropathologies,
      differentiates these phenotypes. In DLB, recent large studies show that clinical
      diagnosis is too insensitive to identify the syndrome itself, although
      clinicopathological studies suggest variable clinical features occur in the
      different pathological forms of this syndrome (pure DLB, DLB with Alzheimer's
      disease (AD), and AD with amygdala predominant Lewy pathology). The recognition
      of considerable heterogeneity within the synucleinopathy syndromes is important
      for the identification of factors involved in changing their pathological
      phenotype.

PMID- 21720850
TI  - The impact of a total laryngectomy on the patients' quality of life.

PMID- 21720851
TI  - A CCD-based fluorescence imaging system for real-time loop-mediated isothermal
      amplification-based rapid and sensitive detection of waterborne pathogens on
      microchips.
AB  - Rapid, sensitive, and low-cost pathogen diagnostic systems are needed for early
      disease diagnosis and treatment, especially in resource-limited settings. This
      study reports a low-cost charge-coupled device (CCD)-based fluorescence imaging
      system for rapid detection of waterborne pathogens by isothermal gene
      amplification in disposable microchips. Fluorescence imaging capability of this
      monochromatic CCD camera is evaluated by optimizing the gain, offset, and
      exposure time. This imaging system is validated for 12 virulence genes of major
      waterborne pathogens on cyclic olefin polymer (COP) microchips, using SYTO-82 dye
      and real time fluorescence loop-mediated isothermal amplification referred here
      as microRT(f)-LAMP. Signal-to-noise ratio (SNR) and threshold time (Tt) of
      microRT(f)-LAMP assays are compared with those from a commercial real-time
      polymerase chain reaction (PCR) instrument. Applying a CCD exposure of 5 s to
      10(5) starting DNA copies of microRT(f)-LAMP assays increases the SNR by 8-fold
      and reduces the Tt by 9.8 min in comparison to a commercial real-time PCR
      instrument. Additionally, single copy level sensitivity for Campylobacter jejuni
      0414 gene is obtained for microRT(f)-LAMP with a Tt of 19 min, which is half the
      time of the commercial real-time PCR instrument. Due to the control over the
      exposure time and the wide field imaging capability of CCD, this low-cost
      fluorescence imaging system has the potential for rapid and parallel detection of
      pathogenic microorganisms in high throughput microfluidic chips.

PMID- 21720852
TI  - HLA-DRB1,-DQA1 and -DQB1 allele and haplotype frequencies in female patients with
      early onset breast cancer.
AB  - Based on the reports, few HLA class II alleles are associated with susceptibility
      or protection in breast cancer. Here we investigate the association between HLA
      class II alleles and breast cancer in Iranian women. 100 patients with
      pathologically proven breast cancer who referred to Cancer Institute were
      randomly selected and compared with a group of 80 healthy blood donor subjects.
      The patients were studied in two groups, group 1 includes patients aging 40 years
      or younger and group 2 include patients aging over 40 years. HLA class II alleles
      were determined by amplification of DNA followed by HLA-typing using sequence
      specific primer (SSP) for each allele. In group 1, the most frequent alleles were
      HLA-DQA1*0301 (P = 0.002, OR = 3.3) and HLA-DQB1*0302 (P = 0.04, OR = 2.8). In
      group 2, the following alleles increased significantly than those in controls
      including HLA-DQA1*0301 (P = 0.001, OR = 3.4) and HLA-DRB1*0301 (P = 0.04, OR =
      2.3). In complete group of patients, the frequency of HLA-DQA1*0301 (P = 0.001,
      OR = 3.4) and HLA-DRB1*1303 (P = 0.02, OR = 2.3) increased significantly than
      those in control group. HLA-DQA1*0505, HLA-DQA1*0101, HLA-DRB1*1301and HLA
      DRB1*0101 alleles showed negative association with breast cancer. Our findings
      suggest that HLA-DQA1*0301 allele is mainly associated with increased risk of
      breast cancer including early-onset of the disease. HLA-DQA1*0505 and HLA
      DRB1*1301 are involved in protection. We conclude that specific alleles of HLA
      class II influence breast cancer risk.

PMID- 21720853
TI  - A comparative evaluation of electrical velocimetry and inert gas rebreathing for
      the non-invasive assessment of cardiac output.
AB  - BACKGROUND: When assessing the function of the cardiovascular system, cardiac
      output (CO) is a substantial parameter. For its determination, numerous non
      invasive techniques have been proposed in the recent years including inert gas
      rebreathing (IGR) and impedance cardiography (ICG). The aim of our study was to
      evaluate whether a novel ICG algorithm (electrical velocimetry) and IGR can be
      used interchangeably in the clinical setting. METHODS: A total of 120 consecutive
      stable patients were included resulting in two pairs of repeated non-invasive
      cardiac output measurements. RESULTS: The mean CO was 5.0 +/- 1.2 l/min (range
      2.6-8.6 l/min) using IGR and 4.4 +/- 1.1 l/min (1.7-7.4 l/min) using ICG,
      respectively. Bland-Altman analysis revealed an acceptable agreement with a mean
      bias of 0.6 +/- 1.2 l/min. We found a high reproducibility with a mean bias of
      0.2 +/- 0.7 l/min for IGR and 0.0 +/- 0.3 l/min for ICG (p < 0.001),
      respectively. There was a statistically significant difference for
      unphysiological circulatory conditions represented by values of 2.6-4.1 l/min and
      5.6-8.6 l/min. CONCLUSIONS: Both non-invasive techniques are associated with low
      operating costs and require only a few expendable items for the rapid
      determination of cardiac function. We found an acceptable agreement between IGR
      and ICG as well as a high reproducibility, which was statistically significant
      higher for ICG. For cardiac output states exceeding the physiological range, we
      found a statistically significant difference. Consequently, values of cardiac
      function determined by either method should not be used interchangeably in the
      clinical setting.

PMID- 21720854
TI  - Examining lifetime episodes of sadness, help seeking, and perceived treatment
      helpfulness among US Latino/as.
AB  - This study investigated episodes of sadness, help seeking for episodes of
      sadness, and perceived treatment helpfulness among Latino/as. Specifically, we
      examined whether gender, ethnicity, and other socio-cultural variables predicted
      episodes of sadness, help seeking, and treatment helpfulness. Data were taken
      from the National Latino Asian American Study which included service use
      questions for episodes of sadness. We stratified the data by service provider and
      used multiple logistic regressions as analytic strategy. Latinas had higher rates
      of episodes of sadness than Latinos, and everyday discrimination was positively
      associated with sadness. Acculturation was associated with more help seeking.
      Puerto Ricans had the highest rates of help seeking, and Mexican-Americans the
      lowest. Discrimination was the strongest predictor of treatment helpfulness from
      any professional as individuals with discriminatory experiences found services
      less helpful. Interventions need to address cultural factors but more focus needs
      to be placed on policies that seek to eliminate inequalities.

PMID- 21720855
TI  - Effects of obstetric factors and storage temperatures on the yield of endothelial
      colony forming cells from umbilical cord blood.
AB  - As umbilical cord blood (UCB) is a rich source of endothelial colony-forming
      cells (ECFC), our aim was twofold: (1) to examine potential obstetric selection
      criteria for achieving the highest ECFC yields from UCB units, and (2) to
      determine whether transient storage temperatures of fresh UCB and
      cryopreservation of UCB units affected ECFC yield and function. ECFC quality was
      assessed before and after cryopreservation by their clonogenic proliferative
      potential. Of the 20 factors examined, placental weight was the only
      statistically significant obstetric factor that predicted ECFC frequency in UCB.
      Studies on the effects of storage revealed that transient storage of fresh UCB at
      4 degrees C reduced ECFC yield compared with storage at 22 degrees C, while
      cryopreservation of UCB MNCs significantly reduced ECFC recoveries. To our
      knowledge, this is the first demonstration that placental weight and temperature
      of storage prior to processing or culture have significant effects on ECFC
      frequency in UCB. Our studies further support the evidence that cryopreservation
      of UCB MNCs compromises ECFC recovery.

PMID- 21720856
TI  - The impact of climate change on ragweed pollination.

PMID- 21720857
TI  - Actinobacteria isolated from termite guts as a source of novel oxidative enzymes.
AB  - A multi-faceted screening programme was designed to search for the oxidases,
      laccase, peroxidase and tyrosinase. Actinobacteria were selectively isolated from
      the paunch and colon region of the hindguts of the higher termite, Amitermes
      hastatus. The isolates were subjected to solid media assays (dye decolourization,
      melanin production and the utilization of indulin AT as sole carbon source) and
      liquid media assays. Eleven of the 39 strains had the ability to decolourize the
      dye RBBR, an indicator for the production of peroxidases in actinobacteria.
      Melanin production on ISP6 and ISP7 agar plates served as a good indicator for
      laccase and/or tyrosinase production and the ability of the strains to grow in
      the presence of indulin AT as a sole carbon source served as a good indicator of
      lignin peroxidase and/or general peroxidase production. Enzyme-producing strains
      were cultivated in liquid media and extracellular enzyme activities measured.
      Strains with the ability to produce oxidative enzymes under the conditions tested
      were identified to genus level by 16S rRNA gene analysis and compared to known
      oxidase producers. A strong relationship was observed between the environment
      sampled (termite guts where lignocellulose degradation occurs) and the dominant
      type of oxidative enzyme activity detected (laccases and peroxidases), which
      suggests the possibility of future targeted screening protocols linking the
      physical properties of the target enzymes with specific operational conditions
      required, such as lignocellulosic degradation in the preparation of biofuel
      feedstocks.

PMID- 21720858
TI  - Pleuropulmonary blastoma in a child with autosomal-recessive polycystic kidney
      disease.
AB  - Autosomal-recessive polycystic kidney disease (ARPKD) is a developmental disorder
      known to affect both the kidneys and the liver. Renal involvement results in
      progressive renal insufficiency and hypertension, while hepatic involvement can
      result in portal hypertension and cholangitis. Pulmonary abnormalities relate
      mainly to pulmonary insufficiency in those patients who present as neonates. We
      present a unique case of a child with ARPKD found to have a cystic lesion of the
      lung. Upon surgical resection, a pathological diagnosis of pleuropulmonary
      blastoma (PPB) was made. There are no previous reports in the literature
      describing the association of these two entities. Knowledge of this potential
      association is important in the clinical management of these children and may
      open new avenues of genetic research.

PMID- 21720859
TI  - Perceived social support and academic achievement: cross-lagged panel and
      bivariate growth curve analyses.
AB  - As students transition to post-secondary education, they experience considerable
      stress and declines in academic performance. Perceived social support is thought
      to improve academic achievement by reducing stress. Longitudinal designs with
      three or more waves are needed in this area because they permit stronger causal
      inferences and help disentangle the direction of relationships. This study uses a
      cross-lagged panel and a bivariate growth curve analysis with a three-wave
      longitudinal design. Participants include 10,445 students (56% female; 12.6% born
      outside of Canada) transitioning to post-secondary education from ages 15-19.
      Self-report measures of academic achievement and a generalized measure of
      perceived social support were used. An increase in average relative standing in
      academic achievement predicted an increase in average relative standing on
      perceived social support 2 years later, but the reverse was not true. High levels
      of perceived social support at age 15 did not protect against declines in
      academic achievement over time. In sum, perceived social support appears to have
      no bearing on adolescents' future academic performance, despite commonly held
      assumptions of its importance.

PMID- 21720860
TI  - Interpersonal competence configurations, attachment to community, and residential
      aspirations of rural adolescents.
AB  - Adolescents who grow-up in rural areas often experience a tension between their
      attachment to the rural lifestyle afforded by their home community and a
      competing desire to gain educational, social, and occupational experiences that
      are only available in metropolitan areas. While these diverging pressures are
      well-documented, there is little information about linkages between rural high
      school students' views of their communities, their postsecondary aspirations, and
      their school adjustment. To address this issue, this study examined perceptions
      of community and residential aspirations in an ethnically diverse sample of 8,754
      rural adolescents (51.5% female) in relationship to their competence and risk
      status in high school. Participants were from 73 rural high schools across 34
      states. In addition, ratings on participants' school adjustment were provided by
      teachers (n = 667). High competence students (i.e., those in configurations of
      high positive and low negative teacher-rated characteristics) expressed positive
      perceptions of their rural lifestyle and many, particularly girls, indicated an
      interest in staying in or returning to their home community. Low competence youth
      (i.e., those in configurations of low positive and high negative teacher-rated
      characteristics) appeared to be less connected to their community and were more
      likely to express their intent to leave and not return. These results appear to
      qualify current concerns about "rural brain drain" and also suggest that the lack
      of attachment to the community may be a compounding risk factor for rural
      adolescents who have significant school adjustment problems.

PMID- 21720861
TI  - Urinary tract infection associated with conditions causing urinary tract
      obstruction and stasis, excluding urolithiasis and neuropathic bladder.
AB  - PURPOSE: The aim of this study was to examine urinary tract infection (UTI)
      associated with conditions causing urinary tract obstruction and stasis,
      excluding urolithiasis and neuropathic bladder dysfunction. METHODS: An
      electronic literature search was performed using the key words urinary tract
      infection (UTI), benign prostatic hyperplasia (BPH), hydronephrosis, obstruction,
      reflux, diverticulum, urethra, and stricture. In total, 520 abstracts were
      reviewed, 210 articles were studied in detail, and 36 were included as
      references. RESULTS: It is one of the axioms of Urological practice that urinary
      tract obstruction and stasis predispose to UTI. Experimental studies indicate
      that, whereas transurethral inoculates of bacteria are rapidly eliminated from
      the normal bladder, urethral obstruction leads to cystitis, pyelonephritis, and
      bacteremia. BPH is, next to urolithiasis, the most common cause of urinary tract
      obstruction predisposing to UTI. Urethral stricture remains a common cause of UTI
      in many parts of the world. Urinary stasis in diverticula of the urethra or
      bladder predisposes to UTI. Experimental studies have shown that, whereas the
      normal kidney is relatively resistant to infection by organisms injected
      intravenously, ureteric obstruction predisposes to pyelonephritis. It also causes
      renal dysfunction which impairs the excretion of antibiotics in the urine, making
      eradication of bacteria difficult. CONCLUSIONS: In patients with UTI and urinary
      tract obstruction, targeted antibiotic treatment according to urine culture
      should be complemented with urgent drainage (bladder catheterization,
      percutaneous nephrostomy or ureteric stenting) followed by definitive surgery to
      remove the cause of obstruction or stasis once infection is under control.

PMID- 21720862
TI  - Biopsy and treatment decisions in the initial management of prostate cancer and
      the role of PCA3; a systematic analysis of expert opinion.
AB  - PURPOSE: The Prostate CAncer gene 3 (PCA3) assay may guide prostate biopsy
      decisions and predict prostate cancer (PCa) aggressiveness. This study explored
      the appropriateness of (1) PCA3 testing; (2) biopsy; (3) active surveillance (AS)
      and the value of the PCA3 Score for biopsy and AS decisions. METHODS: Using the
      RAND/UCLA appropriateness method, 12 urologists assessed the appropriateness of
      PCA3, biopsy and AS for theoretical patient profiles, constructed by combining
      clinical variables. They individually scored the appropriateness for all profiles
      using a 9-point scale. Based on the median score and extent of agreement, the
      appropriateness for each profile was calculated. RESULTS: The PCA3 Assay was
      mainly considered appropriate in men with >=1 negative biopsy, PSA >= 3 ng/mL and
      life expectancy (LE) >=10 years. A LE < 10 years, >=2 negative biopsies and PCA3
      Score <20 decreased biopsy appropriateness, while PSA >= 3 ng/mL and PCA3 Score
      >50 increased it. In men without a prior biopsy, LE >= 10 years and a suspicious
      DRE, PCA3 did not affect biopsy appropriateness. In other men, a PCA3 Score <20
      discouraged biopsy, while a value >=35 supported biopsy. AS was mainly considered
      appropriate if LE < 10 years, T1c PCa, <=20% positive cores and PSA < 3 ng/mL. A
      PCA3 Score <20 pleads for and higher scores (particularly >50) against AS.
      CONCLUSIONS: These findings illustrate in which men PCA3 can be of additional
      value when taking biopsy and treatment decisions in clinical practice.

PMID- 21720863
TI  - Reliability and predictability of the centre-edge angle in the assessment of
      pincer femoroacetabular impingement.
AB  - PURPOSE: The aim of the study was to assess the use of the centre-edge (CE) angle
      in the assessment of pincer femoro-acetabular impingement (FAI) for reliability
      and predictability in the diagnosis. METHODS: Between 2004 and 2008, 55 patients
      underwent surgical treatment for FAI. A control group of 30 was identified among
      patients attending the emergency department with normal radiographs. Radiographs
      were assessed by two independent observers both before and after the operation.
      Nine patients with trauma were excluded. The magnetic resonance arthrogram
      reports of the remaining 46 patients were assessed for pincer FAI. Nineteen
      patients were identified and underwent repeat radiographic assessment. All
      underwent surgical dislocation of hip (SDH), acetabular, with/without femoral
      osteochondroplasty. Acetabular depth and version were also assessed. The
      intraclass correlation (ICC) was used to assess reliability of the CE angle. The
      paired t test and independent groups t test were used to assess the difference
      between the pincer FAI group, both pre-op and post-op and against controls.
      RESULTS: The control and pincer groups were similar in demographics (p=0.1769).
      Coxa profunda was present in 14 patients with eight also having retroverted
      acetabuli. Of the rest two had retroverted acetabuli and one protrusio. The mean
      CE angle in the control group was 31.4 degrees , in the pre-op pincer group 46.2
      degrees  and in the post-op pincer group 38.3 degrees . The ICC for intra
      observer correlation was 0.977 and 0.992 pre-op and 0.986 and 0.974 post-op. The
      ICC for inter-observer correlation was 0.960 and 0.957 pre-op and 0.979 and 0.967
      post-op.The p value was <0.001 between the controls, the pre-op and post-op
      pincer groups. The test characteristics using the CE angle >= 40 is a reasonably
      good predictor of FAI, with a sensitivity of 84.2% and a specificity of 100%.
      CONCLUSIONS: The pincer FAI can be reliably assessed with the CE angle and can be
      predicted in patients presenting with FAI.

PMID- 21720864
TI  - Instrumented stabilization in spinal tuberculosis.
AB  - Spinal tuberculosis (TB) produces neurological complications and grotesque spinal
      deformity, which in children increases even with treatment and after achieving
      healing. Long-standing, severe deformity leads to painful costo-pelvic
      impingement, respiratory distress, risk of developing late-onset paraplegia and
      consequent reduction in quality and longevity of life. The treatment objective is
      to avoid the sequelae of neural complications and achieve the healed status with
      a near-normal spine. In TB, the spine may become unstable if all three columns
      are diseased. Pathological fracture/dislocation of a diseased vertebral body may
      occur secondary to mechanical insult. Surgical decompression adds further
      instability, as part of the diseased vertebral body is excised. The insertion of
      a metallic implant is to provide mechanical stability and the use of an implant
      in tubercular infection is safe. Indications for instrumented stabilisation can
      be categorised as: (a) pan vertebral disease, in which all three columns are
      diseased; (b) long-segment disease, in which after surgical decompression a bone
      graft >5 cm is inserted with instrumentation to prevent graft-related
      complications and consequent progression of kyphosis and neural complications and
      (c) when surgical correction of a kyphosis is performed when both anterior
      decompression and posterior column shortening is required. The implant choice
      should be individualised according to the case. Pedicle screw fixation in kyphus
      correction in healed disease is a most suitable implant. Hartshill sublaminar
      wiring stabilisation in active disease is a suitable implant to stabilise the
      spine, taking purchase against healthy posterior complex of the vertebral body to
      save a segment.

PMID- 21720865
TI  - Heavy metals: their pathway from the ground, groundwater and springs to Lake
      Goreckie (Poland).
AB  - The migration pathways of heavy metals derived from an area previously in
      agricultural use was investigated in the Wielkopolski National Park (mid-western
      Poland). The heavy metals involved (Cd, Cu, Cr, Pb, Ni and Zn) were determined in
      groundwater, the springs that feed Lake Goreckie and the lake itself. In order to
      show how the heavy metals may be set free and what is their biological
      availability, soil and sediment samples were subjected to single-stage
      extraction, using 0.01 M CaCl(2), 0.02 M EDTA, 0.005 M DTPA, 0.1 M HCl, 1 M HCl
      and de-ionised water. Varying metal concentrations were recorded in the water
      samples during the study period (from November 2009 to July 2010), usually with
      higher values in winter and lower ones in summer. The seasonal changes may be
      ascribed to natural processes taking place in the ground- and surface waters of
      Lake Goreckie. On the other hand, the concentration levels (mostly of Cd, Pb and
      Cr) are indicative of anthropogenic activity. It should be mentioned in this
      context that the highest metal concentrations were found in the soil layer. The
      concentrations were also found to exceed both the Polish and the World Health
      Organization water-quality standards. It appears that the soils are highly
      contaminated, mostly with cadmium. The long-lasting effect of acid precipitation
      in the area makes it possible for immobile forms to become mobile, thus
      facilitating further migration into the environment.

PMID- 21720866
TI  - A locus on chromosome 9 is associated with differential response of 129S1/SvImJ
      and FVB/NJ strains of mice to systemic LPS.
AB  - Although polymorphisms in TLR receptors and downstream signaling molecules affect
      the innate immune response, these variants account for only a portion of the
      ability of the host to respond to microorganisms. To identify novel genes that
      regulate the host response to systemic lipopolysaccharide (LPS), we created an F2
      intercross between susceptible (FVB/NJ) and resistant (129S1/SvImJ) strains,
      challenged F2 progeny with LPS via intraperitoneal injection, and phenotyped 605
      animals for survival and another 500 mice for serum concentrations of IL-1beta
      and IL-6. Genome-wide scans were performed on pools of susceptible and resistant
      mice for survival, IL-1beta, and IL-6. This approach identified a locus on the
      telomeric end of the q arm of chromosome 9 (0-40 Mb) that was associated with the
      differences in morbidity and serum concentrations of IL-1beta and IL-6 following
      systemic LPS in FVB/NJ and 129S1/SvImJ strains of mice. Fine mapping narrowed the
      locus to 3.7 Mb containing 11 known genes, among which are three inflammatory
      caspases. We studied expression of genes within the locus by quantitative RT-PCR
      and showed that Casp1 and Casp12 levels are unaffected by LPS in both strains,
      whereas Casp4 is highly induced by LPS in FVB/NJ but not in 129S1/SvImJ mice. In
      conclusion, our mapping results indicate that a 3.7-Mb region on chromosome 9
      contains a gene that regulates differential response to LPS in 129S1/SvImJ and
      FVB/NJ strains of mice. Differences in the induction of Casp4 expression by LPS
      in the two strains suggest that Casp4 is the most likely candidate gene in this
      region.

PMID- 21720867
TI  - Assessing the effects of tertiary treated wastewater reuse on a Mediterranean
      river (Llobregat, NE Spain): pathogens and indicators [corrected].
AB  - PURPOSE: Need, coupled with advances in water treatment technology, is motivating
      a growing interest in augmenting drinking water supplies with reclaimed water.
      Using reclaimed water to increase the flow of the Llobregat River upstream the
      water catchment site of the complex multi-step drinking water treatment plant of
      Sant Joan Despi has been considered. The impact of reclaimed water discharges on
      the load of E. coli, spores of sulphite-reducing clostridia, somatic coliphages,
      cytopathogenic enteroviruses, and total and infectious Cryptosporidium oocysts in
      the Llobregat River water was assessed to gain information for funded decisions
      in potential future emergencies. METHODS: Enterovirus and Cryptosporidium oocysts
      were concentrated from great water volumes prior to enumeration, whereas
      indicators were enumerated directly from the samples. Both indicators and
      pathogens were enumerated by cultural techniques that determine infectious
      microbes. RESULTS AND DISCUSSION: Densities of both indicators and pathogens in
      reclaimed water, despite that it was disinfected by UV irradiation alone or by UV
      irradiation plus chlorination, were significantly lower than their densities in
      the river water, both upstream and downstream the reclaimed water release site in
      the river. CONCLUSION: Results gathered indicate that discharging reclaimed water
      into the river does not increment the load of indicators and pathogens of the
      river water. Then, in emergency situations due to severe water shortages after
      prolonged droughts, at least from the infectious diseases point of view, the
      risks of augmenting drinking water supplies with reclaimed water can be
      satisfactorily and safely managed.

PMID- 21720868
TI  - Cost effectiveness of golimumab for the treatment of active psoriatic arthritis.
AB  - BACKGROUND: Golimumab is a novel TNF-alpha inhibitor licensed to treat patients
      with active PsA. Although its clinical efficacy has been proven in clinical
      trials, its cost effectiveness is yet to be established. OBJECTIVES: To estimate
      the cost effectiveness of golimumab among patients with active PsA from the UK
      NHS perspective. METHODS: A decision analytic model was used to simulate
      progression of a hypothetical cohort of active PsA patients on golimumab and
      other TNF-alpha inhibitors as well as palliative care. The clinical evidence was
      derived from clinical trials of TNF-alpha inhibitors and compared using mixed
      treatment models. The primary outcome measure was quality-adjusted life years
      (QALYs) estimated based on change in Health Assessment Questionnaire (HAQ) and
      Psoriasis Area Severity Index (PASI) from baseline. The annual acquisition cost
      of golimumab was assumed to be identical to annual cost of other subcutaneous TNF
      alpha inhibitors. The resource use costs and outcomes were discounted at 3.5%
      over a period of 40 years. The uncertainty surrounding important variables was
      further explored using probabilistic sensitivity analyses (PSA). RESULTS: TNF
      alpha inhibitors were significantly superior to palliative care but comparable to
      each other on Psoriatic Arthritis Response Criteria (PsARC), HAQ and PASI
      response. The incremental cost effectiveness ratio (ICERs) for golimumab compared
      to palliative care was L16,811 for PsA patients and L16,245 for a subgroup of PsA
      patients with significant psoriasis. At an acceptability threshold of L30,000 per
      QALY, the probability of golimumab being cost effective is 89%. CONCLUSION: Once
      monthly, golimumab is a cost-effective treatment alternative for patients with
      active PsA. With its patient-focussed attributes, golimumab is likely to offer
      additional choice in PsA treatment.

PMID- 21720869
TI  - Multidisciplinary discussion and management of rectal cancer: a population-based
      study.
AB  - BACKGROUND: The purpose of the present study was to evaluate the value of
      discussing rectal cancer patients in a multidisciplinary team (MDT). METHODS: All
      treated rectal cancer patients (>T1M0) diagnosed in 2006-2008 were included.
      According to the national guidelines, neoadjuvant (chemo)radiotherapy should be
      given to all rectal cancer patients. Patients were scored as "discussed" (MDT+)
      only if documented proof was available. The primary endpoint was the number of
      positive circumferential resection margins (CRM <= 1 mm). RESULTS: Of the 275
      patients included, 210 were analyzed (exclusions: (recto)sigmoid tumor, acute
      laparotomy, and inoperability). Neoadjuvant treatment was applied in 174 (83%)
      patients and followed by total mesorectal excision in 171 (81%) patients.
      Patients considered not to require downstaging, received short-course
      radiotherapy (SCRT) (n = 116) or no radiotherapy (no RT) (n = 36), whereas 58
      more advanced patients received chemoradiotherapy (CRT). The MDT discussion took
      place in 116 cases (55%). In the MDT+ group an MRI was used more often (p =
      0.001) and TNM staging was more complete (p < 0.001). The proportion of patients
      with advanced disease was higher in the MDT+ group (88% >=T3/N+ versus 68%; p =
      0.001). The overall CRM+ rate was 13% and did not differ between the MDT+ and the
      MDT- group (p = 0.392). In patients receiving SCRT or no RT, the CRM+ rate was
      10%, whereas the rate was 20% for patients receiving CRT. CONCLUSIONS: Although
      no difference in CRM+ rate was found for those patients who were discussed and
      those who were not, our results demonstrate room for improvement, especially in
      the selection of patients for SCRT or no RT. We advocate standardized
      documentation of treatment decisions and pathology reports.

PMID- 21720871
TI  - [Achalasia in a patient with HIV/HCV coinfection: detection of HCV in the
      esophageal tissue].
AB  - Esophageal involvement in the context of opportunistic infections in human
      immunodeficiency virus (HIV) positive patients is a frequent phenomenon. However,
      worldwide esophageal achalasia has been described only twice in HIV-infected
      patients.We report the case of a 44-year-old Caucasian patient with HIV and
      Hepatitis C virus (HIV/HCV) coinfection who, within 2.5 years, displayed a
      progressive symptomatology with dysphagia, retrosternal pain, regurgitation as
      well as a considerable loss of weight before achalasia was finally diagnosed.
      Treatment was performed primarily surgically by means of laparoscopic Heller
      myotomy with an anterior 180 degrees  semifundoplication according to
      Dor.Histopathology of the specimens taken from the lower esophageal sphincter
      high-pressure zone proved alterations with abundant connective tissue and only
      scarce parts of the smooth muscular system without inflammatory infiltrations. In
      addition, the ganglia cells of the myenteric plexus as well as the interstitial
      cells of Cajal were significantly reduced. Interestingly, specific gene sequences
      of the hepatitis C virus could be detected in the esophageal tissue specimen. In
      contrast, analysis of specific HIV-gene sequences in the same tissue revealed a
      negative result.The possible but previously unknown relationship between
      esophageal achalasia and coinfection with HIV and HCV, also described as
      neurotropic viruses, will be discussed.

PMID- 21720872
TI  - [Postdoctoral qualification regulations of medical faculties in German
      universities. A comparison of 1998 and 2010].
AB  - BACKGROUND: In Germany, Austria and Switzerland the "Habilitation" (postgraduate
      qualification) is currently the highest ranked university degree which qualifies
      candidates to perform high ranking autonomous research and teach the specific
      subject at university level. Although it is legally not an academic degree, the
      habilitation is a mandatory qualification for the later appointment and
      employment as a professor. The habilitation process is a complex assessment of
      diverse prerequisites which differ highly in terms of uniformity among the
      medical faculties in Germany. METHODS: In order to re-evaluate these
      prerequisites and to find out if there might be more conformity for candidates
      all habilitation requirements were analyzed for 12 primary outcome measures
      according to Nagelschmidt and rated with a specific scoring system (Nagelschmidt
      score). RESULTS: The overall scoring for habilitation requirements increased from
      15.2+/-5.1 points in 1998 to 21.9+/-4.0 points in 2010 (95% confidence interval
      20.6-23.3, p<0.001, mainly due to increased requirements in terms of
      publications, teaching and mandatory board certification. No correlation was
      found between the number of habilitation degrees per faculty and the overall
      Nagelschmidt score (y=-0.0545x+26.021, r(2)=0,00028). CONCLUSION: The
      requirements for habilitation have substantially increased by 44% from 1998 to
      2010 in Germany. This is mainly based on higher requirements in terms of
      publications, teaching and board certification.

PMID- 21720873
TI  - An update on molecular genetics of Alkaptonuria (AKU).
AB  - Alkaptonuria (AKU) is an autosomal recessive disorder caused by a deficiency of
      homogentisate 1,2 dioxygenase (HGD) and characterized by homogentisic aciduria,
      ochronosis, and ochronotic arthritis. The defect is caused by mutations in the
      HGD gene, which maps to the human chromosome 3q21-q23. AKU shows a very low
      prevalence (1:100,000-250,000) in most ethnic groups, but there are countries
      such as Slovakia and the Dominican Republic in which the incidence of this
      disorder rises to as much as 1:19,000. In this work, we summarize the genetic
      aspects of AKU in general and the distribution of all known disease-causing
      mutations reported so far. We focus on special features of AKU in Slovakia, which
      is one of the countries with an increased incidence of this rare metabolic
      disorder.

PMID- 21720874
TI  - [A different person in 2 minutes].
AB  - I would like to describe the initial extreme physical and psychological effects
      of my posttraumatic stress disorder that appeared after multiple shocks from an
      implantable cardioverter-defibrillator, my surprise about my physical awareness,
      which I and apparently also the physicians could not understand, the feeling of
      helplessness, the lack of knowledge, the ignorance, and the unfairness of some of
      the physicians concerning my psychological illness, feelings of being stamped as
      a psychopath, not being believed, and being let down, my improvements during the
      course of the last 6 years, my current condition, and my appeal to physicians
      that better care be offered to patients with a similar illness.

PMID- 21720875
TI  - Immunologically restricted patients exhibit a pronounced inflammation and
      inadequate response to hypoxia in fracture hematomas.
AB  - For patients who are known to have an impaired immune system, bone healing is
      often impaired. Therefore, it has been suggested that an effectively functioning
      immune system will have an influence on the quality of bone healing. Here, we
      demonstrate that cells within the fracture hematoma of immunologically restricted
      patients (1) exhibit a disturbed osteogenic differentiation (normal SPP1 but
      diminished RUNX2 expression), (2) show a strong inflammatory reaction (high IL8
      and CXCR4), and (3) react on local hypoxia (high expression of HIF1A) but with
      inadequate target gene responses (diminished LDHA and PGK1 expression). Thus, it
      is already within the early inflammatory phase of fracture healing that the local
      gene expression in fracture hematomas of immunologically restricted patients
      points toward a critical regeneration.

PMID- 21720876
TI  - [Agreement of subjective and objective refraction measurements following INTRACOR
      femtosecond laser treatment].
AB  - BACKGROUND: The goal of this study was to determine the accuracy of
      autorefraction measurements in patients after INTRACOR intrastromal femtosecond
      laser treatment of presbyopia by comparing the agreement between the subjective
      and objective refraction. PATIENTS AND METHODS: In this study the data of 19
      patients with a mean age of 56.5+/-6.0 years following INTRACOR treatment were
      analyzed pre-operatively and 12 months postoperatively. Measurements of the
      subjective refraction and the results of the autorefractor Nidek-660A in miosis
      were compared. INTRACOR is a refractive intrastromal femtosecond laser treatment
      to correct presbyopia. During the procedure a series of five concentric rings in
      the central stroma are cut which cause a change in the curvature of the cornea.
      RESULTS: The differences in sphere and spherical equivalent between subjective
      refraction and autorefraction were not significant (t-test p>0.05 and Wilcoxon
      test p>0.05). Comparing the cylinder of the two measurements a significant
      difference (t-test p<0.05) was found. Focusing on the difference of the
      postoperative measurements of the subjective refraction and autorefraction a
      correlation (within +/-0.5 D) of 89% in the sphere, 100% in cylinder and 68% in
      the spherical equivalent was detected. With one exception the differences in
      sphere, cylinder and the spherical equivalent were within +/-1.25 D. In several
      patients the performance of the autorefraction with the Nidek-660A was somewhat
      complicated and the measures had to be repeated frequently. CONCLUSION: The
      agreement between subjective refraction and objective measurements of the Nidek
      660A of patients following INTRACOR-treatment was good. However there was a
      significant difference in the cylinder values. Therefore thorough comparison of
      measurements obtained with the autorefractor and the subjective refraction is
      recommended.

PMID- 21720877
TI  - Unusual presentations of Hashimoto's encephalopathy: trigeminal neuralgiaform
      headache, skew deviation, hypomania.
AB  - Hashimoto's encephalopathy (HE) is a term used to describe an encephalopathy of
      presumed autoimmune origin characterized by high titers of antithyroid-peroxidase
      antibodies. We describe three patients showing unusual clinical presentations
      like trigeminal-neuralgia, skew deviation, hypomania associated with HE. The
      purpose of this article is to describe the patients with unusual clinical
      pictures of HE, something that has not been reported in elsewhere in medical
      literature.

PMID- 21720878
TI  - Growth hormone effect on body composition in Turner syndrome.
AB  - This study analyzes the body composition of young adult women with Turner
      syndrome (TS) either treated or not treated with recombinant human growth hormone
      (rhGH) and compares them with a group of healthy women. Fifty-two non-treated TS
      patients (23.0 +/- 5.8 years), 30 treated with rhGH (21.5 +/- 1.5 years), and 133
      healthy young adult women (22.9 +/- 3.2 years) were evaluated regarding height
      (H) and weight, body mass index (BMI), brachial perimeter and tricipital
      cutaneous fold (fat and lean areas at the arm), sitting height (SRH = sitting
      height/H * 100), leg length (leg/H), waist and hip circumferences (waist/hip),
      and bioimpedance (percentages of water, lean mass, and fat mass). Age at start of
      rhGH therapy varied from 7.8 to 15.1 years (10.0 +/- 1.3 years), duration of
      treatment from 2.8 to 8.2 years (3.7 +/- 1.5 years), and the mean dose was 0.42
      mg/kg/w (from 0.32 to 0.50 mg/kg/w). Body composition (except height) did not
      differ between TS groups, but there were differences when compared to the control
      group: weight and sitting height were lower in TS patients; and BMI, SHR, and
      leg/H were higher. There was an association between all groups with regards to
      BMI, waist, SHR, and leg/H, but not in percentage of fat mass. SHR was positively
      correlated with BMI, waist, hip, and percentage of fat mass. This sample of TS
      patients (with and without rhGH therapy) did not differ in BMI or body
      composition. However, there were differences between patients with TS patients
      and normal healthy women. Regardless of rhGH therapy, TS patients should be
      monitored, particularly for sitting height, SHR, leg length, leg/H, and
      waist/hip.

PMID- 21720879
TI  - Expression and regulation of adipocyte fatty acid binding protein in granulosa
      cells and its relation with clinical characteristics of polycystic ovary
      syndrome.
AB  - Increased expression of adipocyte fatty acid binding protein (FABP4) is
      associated with type 2 diabetic, high triglycerides, increased lipid
      peroxidation, and inflammation markers. To study the expression of FABP4 mRNA in
      granulosa cells of patients with polycystic ovary syndrome (PCOS) and the impact
      of testosterone, insulin, and PPARgamma agonist rosiglitazone on granulosa cells
      (GCs), and to investigate the relationship of serum FABP4 levels with clinical
      characteristics in patients with PCOS. The expression of FABP4 mRNA in GCs of
      patients with PCOS and normal controls were assayed by RT-PCR. We assessed the
      level of FABP4 mRNA after treatment with testosterone, insulin, and rosiglitazone
      in GCs from normal controls. Serum FABP4 were assayed from 96 patients with PCOS
      (obese and nonobese 48 cases, respectively) and 80 healthy normal controls (obese
      and the nonobese 40 cases, respectively). The expression of FABP4 mRNA was higher
      in the GCs of PCOS than that of the controls (P<0.05). FABP4 mRNA expression was
      up-regulated by testosterone, insulin, and rosiglitazone at different dosages.
      Serum FABP4 levels were higher in the nonobese PCOS group than that of the
      nonobese controls (8.9+/-5.1 ng/ml vs. 4.8+/-0.7 ng/ml), and in the obese PCOS
      group than that of the obese controls (28.2+/-14.0 ng/ml vs. 15.6+/-6.6 ng/ml),
      respectively (P<0.05). Multiple linear regression analyses showed that serum
      FABP4 level was independently associated with HOMA-IR, BMI, and testosterone
      (P<0.05). Increased FABP4 was related to the clinical characteristics of PCOS.

PMID- 21720880
TI  - Metabolic syndrome: its history, mechanisms, and limitations.
AB  - In late twentieth century, Ruderman and Reaven showed that insulin resistance
      might be fundamental to metabolic syndrome (MetS) which means a constellation of
      obesity-related metabolic derangements predisposing to type 2 diabetes and
      cardiovascular disease. In 2001, user-friendly National Cholesterol Education
      Program (NCEP) criteria of MetS were proposed. In 2005, the International
      Diabetes Federation (IDF) and the Examination Committee for Criteria of Metabolic
      Syndrome in Japan issued different criteria of MetS where abdominal obesity is a
      necessary component. In 2009, IDF, National Heart, Lung, and Blood Institute,
      American Heart Association, World Heart Federation, International Atherosclerosis
      Society, and International Association for the Study of Obesity jointly adopted
      the revised NCEP criteria, where abdominal obesity is not a necessary component,
      as worldwide criteria of MetS. In 2010, WHO Expert Consultation warned that MetS
      is a concept that focuses attention on complex multifactorial health problems but
      has limited practical utility as a management tool. In animal studies, adipose
      tissue inflammation characterized by an increased number of crown-like structures
      in adipose tissue, rather than obesity per se, was shown to be a fundamental
      mechanism of metabolic derangements.

PMID- 21720881
TI  - [Current role of minimally invasive total knee arthroplasty. A meta-analysis].
AB  - Minimally invasive approaches are increasingly being used in total knee
      arthroplasty. By means of a review of the literature the pros and cons of
      minimally invasive approaches for total knee arthroplasty were analyzed. The
      potential advantages of reduced postoperative pain and improved early range of
      motion and mobility are opposed by the risks of malpositioning of the prosthetic
      components and impaired wound healing. Long-term improvement of knee function and
      quality of life should not be compromised by techniques promising temporary or
      secondary advantages.

PMID- 21720882
TI  - Non-sensitising air pollution at workplaces and adult-onset asthma in the
      beginning of this millennium.
AB  - PURPOSE: This case-control study was undertaken to elucidate the controversy
      concerning whether low-level, long-term exposure to non-sensitising air pollution
      at workplaces may cause asthma. METHODS: A case-control study of 192 adult-onset
      asthma cases aged 20-65 years and 323 controls was conducted in the southeast of
      Sweden. Cases were identified from computerised registers from the region,
      diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents
      were randomised from the population register of the region. Exposure was
      monitored by a 16-page questionnaire. Special attention was devoted to
      identifying and in the final analyses excluding subjects exposed to sensitising
      agents. RESULTS: Three years or more of occupational exposure to air pollution
      from dust, smoke, fumes or vapours before the year of diagnosis by analyses
      adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2)
      in men, while in women, no risk was seen. In a multiple logistic regression
      analysis in men without allergy in childhood, a significant risk was seen (OR =
      2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were
      excluded. In women, no excess risk was observed from occupational air pollution.
      CONCLUSION: The results of this study support an association between occupational
      exposure to low level non-sensitising air pollution and adult-onset asthma in
      men.

PMID- 21720883
TI  - The aging work force in Korea.
AB  - OBJECTIVES: Korea has the fastest aging population and least fertile population
      of all Organization Economic Cooperation and Development countries, and it is
      undertaking significant preparations for an aging society. So, we want to review
      the present status of Elderly workers' occupational disorders and preparations,
      which is performed by governmental, social parties. METHODS: We examine the
      current status of Korea's aging work force, focusing on occupational disorders
      (injuries and diseases), and retirements, and the associated health effects.
      RESULTS: Despite the efforts and concern about Korea's aging society since the
      issue was first identified, Korea's limited experience in operating a national
      public pension system, and a mature social security system shows that the needs
      of Korea's aging society cannot be fully satisfied. This problem has already
      resulted in increasing labor employment rates and delays in retirement from the
      labor market. CONCLUSIONS: We suggest a policy for elderly workers considering
      various determinants that can lead to successful employment, retirement, and
      health promotion for the aging work force.

PMID- 21720884
TI  - Fluid intake and changes in limb volumes in male ultra-marathoners: does fluid
      overload lead to peripheral oedema?
AB  - An increase in body mass due to oedema has been previously described. The aim of
      this study was to investigate a potential association between both fluid and
      electrolyte intake and the formation of peripheral oedemas. Fluid and electrolyte
      intakes and the changes in limb volumes in 50 male 100-km ultra-marathoners were
      measured. Pre- and post-race serum sodium concentration ([Na(+)]), serum
      aldosterone concentration, serum copeptin concentration, serum and urine
      osmolality and body mass were determined. Fluid intake, renal function parameters
      and urinary output, as well as the changes of volume in the extremities, were
      measured. The changes of volume in the limbs were measured using plethysmography.
      Serum [Na(+)] increased by 1.6%; body mass decreased by 1.9 kg. Serum copeptin
      and aldosterone concentrations were increased. The change in serum copeptin
      concentration and the change in serum [Na(+)] correlated positively; the change
      in serum [Na(+)] and body mass correlated negatively. A mean fluid intake of 0.58
      L/h was positively related to running speed and negatively to post-race serum
      [Na(+)]. Total fluid intake was positively related to the changes in both arm and
      lower leg volumes. Running speed was positively associated with the changes in
      arm and lower leg volumes; race time was related to the changes in serum copeptin
      or aldosterone concentrations. To conclude, fluid intake was related to the
      changes in limb volumes, where athletes with an increased fluid intake developed
      an increase in limb volumes.

PMID- 21720885
TI  - Exercise-induced muscle damage and the repeated bout effect: evidence for cross
      transfer.
AB  - We examined whether a prior bout of eccentric exercise in the elbow flexors
      provided protection against exercise-induced muscle damage in the contralateral
      arm. Fifteen males (age 22.7 +/- 2.1 years; height 178.6 +/- 6.8 cm, mass 75.8 +/
      9.3 kg) were randomly assigned to two groups who performed two bouts of 60
      eccentric contractions (30 degrees /s) separated by 2 weeks: ipsilateral (n = 7,
      both bouts performed in the same arm), contralateral (n = 8, one bout performed
      in each arm). Strength, muscle soreness and resting arm angle (RAA) were measured
      at baseline and at 1, 24 and 48 h post exercise. Surface electromyography was
      recorded during both bouts of exercise. The degree of strength loss was
      attenuated (p < 0.05) in the ipsilateral group after the second bout of eccentric
      exercise (-22 cf. -3% for bout 1 and 2 at 24 h, respectively). Strength loss
      following eccentric exercise was also attenuated (p < 0.05) at 24 h in the
      contralateral group (-30 cf. 13% for bout 1 and 2, respectively). Muscle soreness
      (~34 cf 19 mm) and change in RAA (~5 cf. 3%) were also lower following the second
      bout of eccentric exercise (p < 0.05), although there was no difference in the
      overall change in these values between groups. Median frequency (MF) was
      decreased by 31% between bouts, with no difference between groups. Data support
      observations that the repeated bout effect transfers to the opposite (untrained)
      limb. The similar reduction in MF between bouts for the two groups provides
      evidence for a centrally mediated, neural adaptation.

PMID- 21720886
TI  - Structural features underlying the selectivity of the kinase inhibitors NBC and
      dNBC: role of a nitro group that discriminates between CK2 and DYRK1A.
AB  - 8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a
      fairly potent ATP site-directed inhibitor of protein kinase CK2 (Ki = 0.22 MUM).
      Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the
      latter as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4
      methyl-benzo(g)chromen-2-one (here referred to as "denitro NBC", dNBC), the
      inhibitory power toward CK2 is almost entirely lost (IC(50) > 30 MUM) whereas
      that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor
      of a number of other kinases that are weakly inhibited or unaffected by NBC, with
      special reference to DYRK1A whose IC(50) values with NBC and dNBC are 15 and 0.60
      MUM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent
      inducer of apoptosis is consistent with the notion that this effect is mediated
      by inhibition of endogenous CK2. The structural features underlying NBC
      selectivity have been revealed by inspecting its 3D structure in complex with the
      catalytic subunit of Z. mays CK2. The crucial role of the nitro group is exerted
      both through a direct electrostatic interaction with the side chain of Lys68 and,
      indirectly, by enhancing the acidic dissociation constant of the adjacent
      hydroxyl group which interacts with a conserved water molecule in the deepest
      part of the cavity. By contrast, the very same nitro group is deleterious for the
      binding to the active site of DYRK1A, as disclosed by molecular docking. This
      provides the rationale for preferential inhibition of DYRK1A by dNBC.

PMID- 21720887
TI  - The role of saccades in multitasking: towards an output-related view of eye
      movements.
AB  - The present paper presents an overview of research on the role of saccades in
      multitasking. Multitasking is known to cause performance costs in terms of
      increased response times and/or error rates. However, most of the previous
      research on multitasking was focused on manual and vocal action demands, and the
      role of eye movements has been largely neglected. As a consequence, saccade
      execution was mainly considered with respect to its functional role in gathering
      new visual information (input side of information processing). However, several
      more recent experiments confirmed that saccades both exhibit and cause dual-task
      costs in the context of other actions and should thus also be regarded as a
      response modality (output side of information processing). Theoretical
      implications as well as several open issues for future research will be outlined.

PMID- 21720888
TI  - Rectourethral fistula following laparoscopic radical prostatectomy.
AB  - PURPOSE: To review the outcome of rectourethral fistula sustained during
      laparoscopic radical prostatectomy. METHODS: A retrospective chart review of all
      cases managed at a tertiary referral center. Data abstracted included
      demographics, presenting symptoms, additional interventions, healing, and long
      term functional outcome. RESULTS: Between 2004 and 2009, 10 patients were treated
      for rectourethral fistula following laparoscopic radical prostatectomy. Mean age
      was 60 years. Two patients were converted to open prostatectomy for primary
      repair of the rectal laceration without fecal diversion. The remaining 8 patients
      (80%) had unrecognized injury at the time of prostatectomy and presented
      postoperatively. Mean time from radical prostatectomy to presentation with
      fistula symptoms was 9.5 days. Seven patients (70%) required 1 or more operations
      to treat or control the symptoms of the rectourethral fistula (median 2.3, mean
      2, range 1-4 operations). Three patients (30%) required colostomy within 1 month
      of radical prostatectomy due to severity of symptoms. Spontaneous healing of the
      fistula was noted in 6 patients (60%) following diversion (urinary +/- fecal
      diversion), and a minority of patients (30%) required an operation to close the
      fistula. One patient (10%) required cystectomy for positive margins. During a
      mean follow-up of 27 months, no recurrent fistula was observed in any of the
      patients. All patients had normal anal continence, but the majority of patients
      were incontinent of urine. CONCLUSIONS: Patients who develop a rectourethral
      fistula following laparoscopic radical prostatectomy often require additional
      operations for symptoms control and/or healing of the fistula. Urinary continence
      is affected in the majority of patients.

PMID- 21720889
TI  - Conservative treatment of patients with faecal soiling.
AB  - PURPOSE: A prospective evaluation of fifty patients with faecal soiling but
      normal sphincter function treated by a conservative treatment algorithm. PATIENTS
      AND METHODS: Between January 2010 and January 2011, 50 consecutive patients of
      two different clinical centres, with faecal soiling and normal anorectal function
      as assessed by endoanal ultrasound, MRI and anal manometry, were eligible for the
      purpose of this study. All patients started the therapy by psyllium (PS) and a
      fibre-rich diet daily after 2 months followed by rectal irrigation (RI) in case
      of incomplete response and after 4 months by 4 g colestyramine (CO),
      respectively. The patients completed the Vaizey incontinence score and a 2-week
      diary card. All tests were performed repeated after 2, 4 and 8 months,
      respectively. RESULTS: The study group consisted of 41 men and 9 women and a mean
      age of 38 years (21-70). The soiling complaints resolved completely in 37 (79%)
      patients. After treatment with PS, RI and CO, 12 (24%) patients, 24 (73%)
      patients and 1 (79%) patient, respectively, resolved completely of faecal
      soiling. Average weekly soiling frequency, the amount of patients wearing pads
      daily and the Vaizey incontinence score diminished significantly after treatment
      with psyllium and after treatment with rectal irrigation (P < 0.001). CONCLUSION:
      Conservative treatment focussed on complete evacuation or clearing the anorectal
      canal is effective in the treatment of patients with faecal soiling.

PMID- 21720891
TI  - Influence of intra-operative joint gaps on post-operative flexion angle in
      posterior cruciate-retaining total knee arthroplasty.
AB  - PURPOSE: The purpose of this study is to examine the joint component gap and its
      relationship with post-operative flexion angles in posterior cruciate-retaining
      (CR) total knee arthroplasty (TKA). In posterior-stabilized (PS) TKA, an inverse
      correlation between the joint component gap and the post-operative flexion angle
      was reported. However, the kinematics of the joint component gap has a different
      pattern in PS and CR TKA. It was hypothesised that CR TKA has a different
      correlation between the joint component gap and the post-operative flexion angle
      compared to PS TKA. METHODS: The joint component gap was measured with an offset
      type tensor. The joint component gaps were measured at 0 degrees , 10 degrees ,
      30 degrees , 60 degrees , 90 degrees  and 120 degrees  knee flexion angle and
      various values of the change in the joint component gap were calculated; 10
      degrees -0 degrees , 30 degrees -0 degrees , 60 degrees -0 degrees , 90 degrees 
      0 degrees  and 120 degrees -0 degrees . Multivariate regression analysis was used
      to determine the influencing of these parameters to post-operative knee flexion
      angle. RESULTS: The post-operative flexion angle was positively correlated with a
      joint component gap of 90 degrees  and 120 degrees  and the values of the change
      in the joint component gap of 90 degrees -0 degrees  and 120 degrees -0 degrees .
      Multivariate regression analysis demonstrated pre-operative knee flexion angle,
      and the values of the change in the joint component gap of 90 degrees -0 degrees 
      had a significant independent factor of post-operative knee flexion angle.
      CONCLUSIONS: Post-operative flexion angle is multi-factorial. However, it is
      important to avoid flexion component gap tightness as well as excessive flexion
      component gap looseness for acquisition of better flexion angle in CR TKA. LEVEL
      OF EVIDENCE: IV.

PMID- 21720892
TI  - Comparison of patellar retention versus resurfacing in LCS mobile-bearing total
      knee arthroplasty.
AB  - PURPOSE: The aim of this retrospective study was to compare clinical outcomes of
      total knee arthroplasty (TKA) with and without patellar resurfacing using the Low
      Contact Stress (LCS) mobile-bearing prosthesis in 275 osteoarthritic knees (199
      patients) after a minimum of 7 years of follow-up. METHODS: Patients were divided
      into a patellar retention group (132 knees) and a resurfacing group (143 knees),
      with median follow-up durations of 7.8 years (range, 7-8.5 years) and 8.5 years
      (range, 7-10.6 years), respectively. The demographics of the two groups were
      otherwise matched. The patelloplasty was performed for patellar retention.
      Patients were evaluated by a blinded, independent observer using Feller's
      patellar score, the Knee Society score, patient satisfaction, patellar tilt, and
      lateral displacement. RESULTS: Patellar resurfacing was not superior to retention
      with respect to any of the measured variables. Eight knees (6.1%) without and 6
      (4.2%) with patellar resurfacing had anterior knee pain related to the
      patellofemoral joint (n.s.). The reoperation rate related to the patellofemoral
      joint was 0.8% (n = 1) in the retention group compared with 2.8% (n = 4) in the
      resurfacing group (n.s.). In the 35 patients who underwent bilateral TKA with
      patellar resurfacing on only one side, there were no significant differences
      between the two sides in subjective preference, clinical scores, or functional
      ability. CONCLUSIONS: The clinical and radiographic outcomes of TKA with the LCS
      mobile-bearing prosthesis showed no significant difference between the two groups
      after a minimum of 7 years of follow-up. The findings in this study suggest that
      patellar retention with a patelloplasty may be viable as a routine procedure,
      even in knees with advanced patellofemoral arthritis, if soft tissue balancing
      and a patella-friendly prosthetic design are properly used. LEVEL OF EVIDENCE:
      Therapeutic, retrospective, comparative study, Level III.

PMID- 21720893
TI  - Lumbar spine bone mineral density in US adults: demographic patterns and
      relationship with femur neck skeletal status.
AB  - This analysis examines lumbar spine bone mineral density (BMD) of US adults from
      NHANES 2005-2008 by age, sex, and race/ethnicity. Prevalence of low spine BMD and
      agreement between the prevalence of low BMD at the spine and femur neck in older
      adults are also assessed. INTRODUCTION: Lumbar spine BMD data from a
      representative sample of the US population have not been previously available.
      METHODS: We used data from the National Health and Nutrition Examination Survey
      2005-2008 to examine demographic patterns in lumbar spine BMD among US adults age
      >=20 years and the prevalence of low lumbar spine BMD in adults age >=50 years.
      Agreement between the prevalence of low BMD at the femur neck and spine in older
      adults was also assessed. Dual-energy X-ray absorptiometry was used to measure
      lumbar spine and femur neck BMD. World Health Organization definitions were used
      to categorize skeletal status as normal, osteopenia, or osteoporosis. RESULTS:
      Compared to non-Hispanic whites, non-Hispanic blacks had higher and Mexican
      Americans had lower lumbar spine BMD. Lumbar spine BMD declined with age in
      women, but not in men. Approximately 4.7 million (10%) older US women and 1
      million (3%) older men had lumbar spine osteoporosis in 2005-2008. Roughly one
      third of them differed in skeletal status at the spine and hip but most were
      normal at one site and osteopenic at the other. Only 3-10%, depending on sex, had
      osteoporosis at one skeletal site but not at the other skeletal site. Between 76%
      and 87% with discordant skeletal status had lumbar spine T-scores within 1 unit
      of the category threshold. CONCLUSIONS: These findings suggest that measuring
      either the femur neck or the lumbar spine will correctly classify the majority of
      individuals who present for care as osteoporotic or not.

PMID- 21720894
TI  - The impact of pharmacist interventions on osteoporosis management: a systematic
      review.
AB  - We completed a systematic review of the literature to examine the impact of
      pharmacist interventions in improving osteoporosis management. Results from
      randomized controlled trials suggest that pharmacist interventions may improve
      bone mineral density testing and calcium intake among patients at high risk for
      osteoporosis. INTRODUCTION: Pharmacists play a key role in many healthcare
      systems by helping patients manage chronic diseases. We completed a systematic
      review of the literature to identify randomized controlled trials (RCTs) that
      have examined the impact of pharmacy interventions in narrowing two gaps in
      osteoporosis management: identifying at-risk individuals and improving adherence
      to therapy. METHODS: We searched the electronic databases of EMBASE, HealthStar,
      International Pharmaceutical Abstracts, MEDLINE, and PubMed from database
      development to April 2010, examined grey literature, and completed manual
      searches of reference lists to identify English-language research that examined
      osteoporosis management interventions within pharmacy practice. Results from RCTs
      were abstracted and assessed for bias. RESULTS: We identified 25 studies that
      examined pharmacist interventions in osteoporosis management: 16 cohort, 5 cross
      sectional, 1 historical/ecological control, and 3 RCTs. RCT interventions
      included osteoporosis educational and counseling programs, screening by
      pharmacists based on risk factor assessment or bone mineral density testing, and
      physician contact or recommendations for patients to follow-up with a general
      practitioner. Results from the three RCTs suggest that pharmacist interventions
      may improve bone mineral density testing (targeted screening) and calcium intake
      among patients at high risk for osteoporosis. However, two of the three RCTs had
      high risk of bias, and no study examined the impact of pharmacist intervention on
      osteoporosis treatment adherence. CONCLUSIONS: Data support the potential role
      for pharmacists to help reduce gaps in osteoporosis management through improved
      identification of high-risk patients. More research is needed to examine
      pharmacist interventions on osteoporosis treatment adherence.

PMID- 21720895
TI  - Continuous involuntary hand movements and schizencephaly: epilepsia partialis
      continua or dystonia?
AB  - Schizencephaly is regarded as a malformation of cortical development (due to
      abnormal neuronal organization) and may be associated with continuous involuntary
      hand movements. The mechanisms underlying these movements are not clear and both
      dystonia and epilepsia partialis continua have been considered in previously
      reported cases. We describe a young patient affected by schizencephaly and
      continuous involuntary movements of the contralateral hand. Functional MRI showed
      bilateral cerebral activation, while the subject performed tapping movements with
      the affected hand and no significant difference in the activation pattern after
      diazepam infusion. Standard and back-averaged EEG showed no alterations. The
      results obtained from these investigations and the clinical features of the
      involuntary movements are not in favor of an epileptic genesis, while support the
      diagnosis of secondary dystonia.

PMID- 21720896
TI  - A case of cerebellar infarction presenting as thunderclap headache.
AB  - Thunderclap headache (TCH) refers to a sudden-onset, severe headache that
      features in subarachnoid hemorrhage, unruptured intracranial aneurysm, cerebral
      venous thrombosis, pituitary apoplexy, cervical artery dissection, and
      hypertensive reversible posterior leukoencephalopathy. TCH is a rare
      manifestation in cerebral or cerebellar infarctions. Herein, we report on a 60
      year-old woman with a thunderclap headache as the first symptom of cerebellar
      infarction, in the absence of abnormal findings in the brain computed tomography
      (CT), CT angiography, and lumbar puncture. An urgent brain MRI showed an acute
      infarction of the right cerebellar hemisphere. The next day, the patient
      presented with right side ataxia. In emergency cases presenting with thunderclap
      headache, one should consider an expanded evaluation and/or close observation,
      with frequent neurological examinations, even though the findings are normal on
      the initial neurological examination, cerebrospinal fluid analysis, and brain CT.

PMID- 21720897
TI  - The medial plantar and medial peroneal cutaneous nerve conduction studies for
      diabetic polyneuropathy.
AB  - Objective of this study was to determine which nerve conduction is more sensitive
      electrophysiologically in the diagnosis of polyneuropathy in diabetics by
      evaluating the sensory conduction in medial plantar nerve and medial peroneal
      (dorsal) cutaneous nerves. Additionally to investigate the relation between
      Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) values used
      in the diagnosis of these conduction studies. Forty patients with diagnosis
      diabetic neuropathy were included into this study. In diabetic polyneuropathic
      patient group, both medial plantar and medial dorsal cutaneous nerve sensory
      action potential were not bilaterally obtained in 19 patients (47.5%).
      Sensitivity and specificity of medial dorsal cutaneous nerve and medial plantar
      nerve sensory conduction abnormalities in diagnosis of diabetic polyneuropathy
      were higher compared to sural nerve conduction abnormalities. This study showed
      that both medial plantar and medial dorsal cutaneous nerve conduction study
      performed bilaterally was a highly sensitive and specific method in diagnosis of
      diabetic neuropathy.

PMID- 21720898
TI  - Cefixime-induced nonconvulsive status epilepticus.
AB  - Nonconvulsive status epilepticus (NCSE) is an epileptic condition lasting >30
      min, clinically manifested by an altered mental state and associated with
      continuous epileptiform activity on the electroencephalogram. NCSE is a common
      yet still under recognized condition and delay in diagnosis and treatment may be
      associated with increased mortality as well as cognitive/behavioral consequences.
      We described an epileptic female patient assuming carbamazepine (900 mg/day) and
      levetiracetam (3,000 mg/day), seizure free for more than 10 years, who developed
      NCSE during cefixime treatment, a third-generation cephalosporin compound that
      along with penicillins is classified within the b-lactam class of antibiotics. In
      our report we outline the importance and the difficulty to choose secure
      antibiotic treatment in epileptic patients, we discuss the possible mechanisms by
      which cephalosporins induce neurotoxicity and the need to stress family
      components questioning about new drugs assumed. Finally we highlight the value of
      the EEG recording to diagnose NCSE and treat it adequately and promptly.

PMID- 21720899
TI  - Do the quantitative relationships of synaptic junctions and terminals in the
      thalamus of genetic absence epilepsy rats from Strasbourg (GAERS) differ from
      those in normal control Wistar rats.
AB  - Abnormal functional properties of the thalamocortical connections were reported
      in the absence of epilepsy. The present study compares the ratios of terminals
      ('RL'-round vesicles, large terminals, 'RS'-round vesicles, small terminals and
      'F'-flattened vesicles) and synapse in three first-order (ventrobasal, lateral
      geniculate and anteroventral) and in three higher-order (posterior, lateral
      posterior and mediodorsal) thalamic nuclei of genetic absence epilepsy rats from
      Strasbourg (GAERS) with our earlier quantitative studies of normal Wistar rats to
      show whether quantitative differences were present in GAERS as compared to Wistar
      rat. Rats were perfused transcardially, the brains were removed and cut as 300
      MUm coronal sections. Parts of the six thalamic nuclei were removed for routine
      electron microscopy and GABA immunocytochemistry. Twenty photographs from each
      section at 20,000* magnification were taken, and the terminals were identified as
      RL, RS or F. (1) In normal Wistar rats (as in cats), the proportion of driver
      terminals (RL) and synapses is lower in higher-order than in first-order thalamic
      nuclei, but this difference is not present in GAERS animals. (2) The proportions
      of RS terminals and synapses for each thalamic nucleus showed no significant
      differences between GAERS and Wistar rats for any of the thalamic nuclei. (3) In
      GAERS, the proportion of inhibitory F terminals and synapses was significantly
      high in the VB and low in the LP thalamic nucleus. These abnormal ratios in the
      GAERS may be the cause of the spike-and-wave discharges of absence seizures or
      may represent a compensatory response of the thalamocortical circuitry to the
      absence seizures.

PMID- 21720900
TI  - Delayed neuroprotection induced by sevoflurane via opening mitochondrial ATP
      sensitive potassium channels and p38 MAPK phosphorylation.
AB  - This study aimed to investigate the role of p38 MAPK phosphorylation and opening
      of the mitoK(ATP) channels in the sevoflurane-induced delayed neuroprotection in
      the rat brain. Adult male Sprague-Dawley rats (250-300 g) were randomly assigned
      into four groups: ischemia/reperfusion (Control), sevoflurane (Sevo), 5
      hydroxydecanoate (5-HD) + sevoflurane (5-HD + Sevo) and 5-HD groups and were
      subjected to right middle cerebral artery occlusion (MCAO) for 2 h. Sevoflurane
      preconditioning was induced 24 h before MCAO in sevoflurane and 5-HD +
      sevoflurane groups by exposing the animals to 2.4% sevoflurane in oxygen for 60
      min. In control and 5-HD groups: animals were exposed to oxygen for 60 min at 24
      h before MCAO. A selective mitoK(ATP) channel antagonist, 5-hydroxydecanoate (5
      HD, 40 mg/kg, i.p.), was administered 30 min before sevoflurane/oxygen exposure
      in the 5-HD + sevoflurane and 5-HD groups, respectively. Neurological deficits
      scores and the protein expression of phosphorylated p38 mitogen-activated protein
      kinase (p-p38 MAPK) were evaluated at 24 and 72 h after reperfusion. Cerebral
      infarct size was evaluated at 72 h after reperfusion by 2,3,5
      triphenyltetrazolium chloride staining. Sevoflurane preconditioning produced
      marked improvement neurological functions and a reduction in brain infarct
      volumes than animals with brain ischemia only. Sevoflurane treatment also caused
      increased phosphorylation of p38 MAPK at 24 and 72 h after reperfusion. These
      beneficial effects were attenuated by 5-HD. Blockade of cerebral protection with
      5-HD concomitant with decrease in p38 phosphorylation suggests that mitoK(ATP)
      channels opening and p38 phosphorylation participate signal transduction cascade
      of sevoflurane preconditioning and p38 MAPK activation may be a downstream of
      opening mitoK(ATP) channels.

PMID- 21720901
TI  - Neurological complications in hyperemesis gravidarum.
AB  - Hyperemesis gravidarum can impair correct absorption of an adequate amount of
      thiamine and can cause electrolyte imbalance. This study investigated the
      neurological complications in a pregnant woman with hyperemesis gravidarum. A 29
      year-old pregnant woman was admitted for hyperemesis gravidarum. Besides
      undernutrition, a neurological examination disclosed weakness with hyporeflexia,
      ophthalmoparesis, multidirectional nystagmus and optic disks swelling; the
      patient became rapidly comatose. Brain MRI showed symmetric signal hyperintensity
      and swelling of periaqueductal area, hypothalamus and mammillary bodies, medial
      and posterior portions of the thalamus and columns of fornix, consistent with
      Wernicke encephalopathy (WE). Neurophysiological studies revealed an axonal
      sensory-motor polyneuropathy, likely due to thiamine deficiency or critical
      illness polyneuropathy. Sodium and potassium supplementation and parenteral
      thiamine were administered with improvement of consciousness state in a few days.
      WE evolved in Korsakoff syndrome. A repeat MRI showed a marked improvement of WE
      related alterations and a new hyperintense lesion in the pons, suggestive of
      central pontine myelinolysis. No sign or symptom due to involvement of the pons
      was present.

PMID- 21720902
TI  - In memoriam: Dr. Charles J. Epstein (1933-2011).

PMID- 21720903
TI  - Decreased expression in nuclear factor-kappaB essential modulator due to a novel
      splice-site mutation causes X-linked ectodermal dysplasia with immunodeficiency.
AB  - X-linked ectodermal dysplasia with immunodeficiency (XL-ED-ID) is caused by
      hypomorphic mutations in NEMO, which encodes nuclear factor-kappaB (NF-kappaB)
      essential modulator. We identified a novel mutation, 769-1 G>C, at the splicing
      acceptor site of exon 7 in NEMO in a Japanese patient with XL-ED-ID. Although
      various abnormally spliced NEMO messenger RNAs (mRNAs) were observed, a small
      amount of wild-type (WT) mRNA was also identified. Decreased NEMO protein
      expression was detected in various lineages of leukocytes. Although one
      abnormally spliced NEMO protein showed residual NF-kappaB transcription activity,
      it did not seem to exert a dominant-negative effect against WT-NEMO activity.
      CD4(+) T cell proliferation was impaired in response to measles and mumps, but
      not rubella. These results were consistent with the clinical and laboratory
      findings of the patient, suggesting the functional importance of NEMO against
      specific viral infections. The 769-1 G>C mutation is responsible for decreased WT
      NEMO protein expression, resulting in the development of XL-ED-ID.

PMID- 21720904
TI  - Attention to inpatients' religious and spiritual concerns: predictors and
      association with patient satisfaction.
AB  - BACKGROUND: Little is known about how often patients desire and experience
      discussions with hospital personnel regarding R/S (religion and spirituality) or
      what effects such discussions have on patient satisfaction. OBJECTIVE, DESIGN AND
      PARTICIPANTS: We examined data from the University of Chicago Hospitalist Study,
      which gathers sociodemographic and clinical information from all consenting
      general internal medicine patients at the University of Chicago Medical Center.
      MAIN MEASURES: Primary outcomes were whether or not patients desired to have
      their religious or spiritual concerns addressed while hospitalized, whether or
      not anyone talked to them about religious and spiritual issues, and which member
      of the health care team spoke with them about these issues. Primary predictors
      were patients' ratings of their religious attendance, their efforts to carry
      their religious beliefs over into other dealings in life, and their spirituality.
      KEY RESULTS: Forty-one percent of inpatients desired a discussion of R/S concerns
      while hospitalized, but only half of those reported having such a discussion.
      Overall, 32% of inpatients reported having a discussion of their R/S concerns.
      Religious patients and those experiencing more severe pain were more likely both
      to desire and to have discussions of spiritual concerns. Patients who had
      discussions of R/S concerns were more likely to rate their care at the highest
      level on four different measures of patient satisfaction, regardless of whether
      or not they said they had desired such a discussion (odds ratios 1.4-2.2, 95%
      confidence intervals 1.1-3.0). CONCLUSIONS: These data suggest that many more
      inpatients desire conversations about R/S than have them. Health care
      professionals might improve patients' overall experience with being hospitalized
      and patient satisfaction by addressing this unmet patient need.

PMID- 21720905
TI  - Association between socioeconomic status (SES) and lower urinary tract symptom
      (LUTS) severity among black and white men.
AB  - BACKGROUND: A higher prevalence of moderate or severe lower urinary tract
      symptoms (LUTS) has been reported among African Americans, but the separate
      effects of race and socioeconomic status (SES) on LUTS severity are unclear.
      OBJECTIVE: We investigated the roles of education, income, marital status, and
      source of health insurance on LUTS reporting among black and white U.S. men.
      DESIGN: A prospective cohort within the Southern Community Cohort Study MAIN
      MEASURES: The International Prostate Symptom Score (IPSS) was completed during
      follow-up by 2488 white men and 4188 black men. Multivariable linear and logistic
      regression methods were used to compare IPSS scores and LUTS severity by race and
      SES after adjusting for age, duration of follow-up, benign prostatic hyperplasia
      (BPH) treatment, source of recruitment, smoking status, BMI, mode of follow-up
      ascertainment, and prior diagnosis of hypertension, diabetes, or
      hypercholesterolemia. KEY RESULTS: Overall IPSS scores and the prevalence of
      moderate/severe LUTS were not significantly associated with race. Instead, higher
      IPSS scores were significantly associated (p < 0.05) with a lower income, marital
      status, and source of insurance. Education was also marginally associated with
      IPSS scores (p = 0.06) among black men. Furthermore, moderate/severe LUTS onset
      was significantly associated with a household income less than $15,000/year (OR =
      1.56 (1.23, 1.96)) and having private health insurance (OR = 0.79 (0.67, 0.93)).
      CONCLUSIONS: Social or behavioral factors related to SES affect LUTS reporting,
      and suggests a potential affect on BPH diagnosis.

PMID- 21720906
TI  - Pneumatosis coli--an underrecognized lesion mimicking neoplastic disease.
AB  - Pneumatosis (cystoides) intestinalis is defined as the presence of gas in the
      bowel wall and can be found anywhere in the gastrointestinal tract. It may be
      harmless or life-threatening, depending on the etiology which includes infectious
      and drug-induced colitis, bowel ischemia and necrotizing enterocolitis. The
      lesion has additionally been described following endoscopy. We report two cases
      of asymptomatic pneumatosis coli mimicking polyposis syndrome or malignancy. Both
      cases were verified histologically after snare polypectomy or hemicolectomy. The
      differential diagnosis and the clinical significance of the disease are
      discussed. Accurate diagnosis, which is mainly based upon endoscopy, computed
      tomography and histology, is crucial for optimal patient management thus avoiding
      unnecessary surgical procedures.

PMID- 21720907
TI  - Left ventricular function-conduction impairment as reflected by the ECG in
      chronic aortic regurgitation.
AB  - The study was conducted to ascertain that the ECG assists in the assessment of
      systolic dysfunction in chronic aortic regurgitation. Five variables were
      reviewed in 146 adults without bundle branch block who underwent
      angiocardiography: total 12-lead QRS amplitude, QRS duration, maximum R peak time
      in I, V5 or V6, maximum R peak time relative to S peak time of the maximum S in
      V1, V2 or V3, and maximum T wave amplitude and polarity in I, V6 or aVF. In order
      to define which of them could differentiate left ventricular ejection fraction
      (EF) >=50% (n = 101) from EF <50% (n = 45) they were subjected to stepwise linear
      discriminant analysis. The maximum R peak time relative to S peak time emerged as
      the most promising variable. In predicting EF <50%, R peak time prolongation
      exceeding S peak time, i.e. R peak delay, yields reliable results, with
      specificity, positive and negative predictive value being 89.1%, 70.3% and 82.6%,
      respectively, and sensitivity being 57.8%. As given by the sample odds-ratio, R
      peak delay indicates an 11-fold increased risk of having EF <50%. R peak delay, a
      marker of left ventricular function-conduction impairment identifies patients who
      need valve replacement.

PMID- 21720908
TI  - Multispectral optoacoustic tomography of matrix metalloproteinase activity in
      vulnerable human carotid plaques.
AB  - AIMS: Elevated expression of cathepsins, integrins and matrix metalloproteinases
      (MMPs) is typically associated with atherosclerotic plaque instability. While
      fluorescent tagging of such molecules has been amply demonstrated, no imaging
      method was so far shown capable of resolving these inflammation-associated tags
      with high fidelity and resolution beyond microscopic depths. This study is aimed
      at demonstrating a new method with high potential for noninvasive clinical
      cardiovascular diagnostics of vulnerable plaques using high-resolution deep
      tissue multispectral optoacoustic tomography (MSOT) technology. METHODS AND
      RESULTS: MMP-sensitive activatable fluorescent probe (MMPSenseTM 680) was applied
      to human carotid plaques from symptomatic patients. Atherosclerotic activity was
      detected by tuning MSOT wavelengths to activation-dependent absorption changes of
      the molecules, structurally modified in the presence of enzymes. MSOT analysis
      simultaneously provided morphology along with heterogeneous MMP activity with
      better than 200 micron resolution throughout the intact plaque tissue. The
      results corresponded well with epi-fluorescence images made from thin
      cryosections. Elevated MMP activity was further confirmed by in situ zymography,
      accompanied by increased macrophage influx. CONCLUSIONS: We demonstrated, for the
      first time to our knowledge, the ability of MSOT to provide volumetric images of
      activatable molecular probe distribution deep within optically diffuse tissues.
      High-resolution mapping of MMP activity was achieved deep in the vulnerable
      plaque of intact human carotid specimens. This performance directly relates to
      pre-clinical screening applications in animal models and to clinical decision
      potential as it might eventually allow for highly specific visualization and
      staging of plaque vulnerability thus impacting therapeutic clinical decision
      making.

PMID- 21720909
TI  - A physiologic comparison of proportional assist ventilation with load-adjustable
      gain factors (PAV+) versus pressure support ventilation (PSV).
AB  - PURPOSE: To compare patient-ventilator interaction during PSV and PAV+ in
      patients that are difficult to wean. METHODS: This was a physiologic study
      involving 11 patients. During three consecutive trials (PSV first trial--PSV1,
      followed by PAV+, followed by a second PSV trial--PSV2, with the same settings as
      PSV1) we evaluated mechanical and patient respiratory pattern; inspiratory effort
      from excursion Pdi (swing(Pdi)), and pressure-time products of the
      transdiaphragmatic (PTPdi) pressures. Inspiratory (delay(trinsp)) and expiratory
      (delay(trexp)) trigger delays, time of synchrony (time(syn)), and asynchrony
      index (AI) were assessed. RESULTS: Compared to PAV+, during PSV trials, the
      mechanical inspiratory time (Ti(flow)) was significantly longer than patient
      inspiratory time (Ti(pat)) (p < 0.05); Ti(pat) showed a prolongation between PSV1
      and PAV+, significant comparing PAV+ and PSV2 (p < 0.05). PAV+ significantly
      reduced delay(trexp) (p < 0.001). The portion of tidal volume (VT) delivered in
      phase with Ti(pat) (VT(pat)/VT(mecc)) was significantly higher during PAV+ (p <
      0.01). The time of synchrony was significantly longer during PAV+ than during PSV
      (p < 0.001). During PSV 5 patients out of 11 showed an AI greater than 10%,
      whereas the AI was nil during PAV+. CONCLUSION: PAV+ improves patient-ventilator
      interaction, significantly reducing the incidence of end-expiratory asynchrony
      and increasing the time of synchrony.

PMID- 21720910
TI  - Increased RNA editing in children with cyanotic congenital heart disease.
AB  - PURPOSE: To test the hypothesis that RNA editing is altered in pediatric patients
      with cyanotic congenital heart disease (CHD) and to determine whether A-to-I RNA
      editing is associated with the postoperative course following cardiac surgery.
      Cyanotic CHD is associated with a unique pathophysiology caused by chronic
      hypoxia. The perioperative course of cyanotic infants is partly dictated by the
      degree of expression of inflammatory and cardiac genes, some of which undergo A
      to-I RNA editing. METHODS: RNA was extracted pre- and postoperatively from blood
      samples of cyanotic and acyanotic patients. Each sample was analyzed for A-to-I
      RNA editing using automatic DNA sequencing of an intronic segment of the MED13
      gene. RNA expression levels of adenosine deaminase acting on RNA (ADAR) enzymes
      responsible for RNA editing were examined by quantitative reverse-transcriptase
      polymerase chain reaction. RESULTS: A-to-I RNA editing in MED13 was significantly
      higher among cyanotic patients (n = 19) than acyanotic ones (n = 18) both pre-
      and postoperatively, as manifested by average editing at seven highly edited
      sites (27.4 +/- 8.5% versus 20.8 +/- 10.2%; P = 0.038) and editing at specific
      sites, e.g., position 14 (20.2 +/- 5.1% versus 14.5 +/- 5.2%; P = 0.002).
      Cyanotic patients exhibited a more complicated postoperative course than
      acyanotic patients. ADAR2 RNA levels were significantly lower among cyanotic
      patients. CONCLUSIONS: Cyanotic children manifest significantly higher rates of A
      to-I RNA editing than acyanotic children as well as a more complicated surgical
      course. Posttranscriptional RNA changes may affect cellular and metabolic
      pathways and influence the perioperative course following hypoxia.

PMID- 21720911
TI  - ESR1, FTO, and UCP2 genes interact with bariatric surgery affecting weight loss
      and glycemic control in severely obese patients.
AB  - BACKGROUND: Significant variability in weight loss and glycemic control has been
      observed in obese patients receiving bariatric surgery. Genetic factors may play
      a role in the different outcomes. METHODS: Five hundred and twenty severely obese
      patients with body mass index (BMI) >=35 were recruited. Among them, 149 and 371
      subjects received laparoscopic adjustable gastric banding (LAGB) and laparoscopic
      mini-gastric bypass (LMGB), respectively. All individuals were genotyped for five
      obesity-related single nucleotide polymorphisms on ESR1, FTO, PPARgamma, and UCP2
      genes to explore how these genes affect weight loss and glycemic control after
      bariatric surgery at the 6th month. RESULTS: Obese patients with risk genotypes
      on rs660339-UCP2 had greater decrease in BMI after LAGB compared to patients with
      non-risk genotypes (-7.5 vs. -6 U, p = 0.02). In contrast, after LMGB, obese
      patients with risk genotypes on either rs712221-ESR1 or rs9939609-FTO had
      significant decreases in BMI (risk vs. non-risk genotype, -12.5 vs. -10.0 U on
      rs712221, p = 0.02 and -12.1 vs. -10.6 U on rs9939609, p = 0.04) and a
      significant amelioration in HbA1c levels (p = 0.038 for rs712221 and p < 0.0001
      for rs9939609). The synergic effect of ESR1 and FTO genes on HbA1c amelioration
      was greater (-1.54%, p for trend <0.001) than any of these genes alone in obese
      patients receiving LMGB. CONCLUSIONS: The genetic variants in the ESR, FTO, and
      UCP2 genes may be considered as a screening tool prior to bariatric surgery to
      help clinicians predict weight loss or glycemic control outcomes for severely
      obese patients.

PMID- 21720912
TI  - Transvaginal mesh surgery for pelvic organ prolapse--Prolift+M: a prospective
      clinical trial.
AB  - INTRODUCTION AND HYPOTHESIS: This study deals with assessment of safety,
      efficacy, and potential complications of Prolift+M system to correct uterovaginal
      prolapse. METHODS: We analyzed a prospective cohort treated with the Gynecare
      PROLIFT+M mesh system between October 2008 and March 2010. A composite score that
      included subjective/objective cure and lack of complications was used to assess
      treatment success. RESULTS: One hundred sixty-seven women (age 65.1 +/- 11.2
      years, BMI 29.2 +/- 5.8 kg/m(2)) were treated for pelvic organ prolapse using the
      PROLIFT+M system. Seven anterior Prolift+M, 42 posterior Prolift+M, and 118 total
      Prolift+M mesh surgeries were performed in patients with stage II or greater
      degrees of prolapse. Mean operative time was 122.7 +/- 43.9 min. Mean
      intraoperative blood loss was 119.4 +/- 125.3 ml. Our composite success score was
      72.5% (treatment failures per POP-Q stage 1.4%, perception of bulge 4.4%,
      erosions 3.6%, pain/dyspareunia 3.7%, incontinence 0.7%, de novo urge urinary
      incontinence 8.7%, voiding dysfunction 0.6%, recurrent urinary tract infection
      2.2%, and anal incontinence 2.2%). CONCLUSIONS: Prolift+M surgery is safe and
      effective with minimal postoperative morbidities.

PMID- 21720913
TI  - Monoprosthesis for anterior vaginal prolapse and stress urinary incontinence:
      midterm results of an international multicentre prospective study.
AB  - INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) can occur
      simultaneously with anterior vaginal prolapse (AVP) in up to 30% of patients. We
      studied a monoprosthesis that combines prepubic and transobturator arms for
      simultaneous treatment of AVP and SUI. METHODS: One hundred four women with AVP
      underwent surgical treatment using a monoprosthesis (NAZCA TC). POP-Q was used
      for anatomical evaluation. Functional results were evaluated by quality of life
      questionnaires, stress test and Stamey score. Patients were evaluated at 1, 3, 6
      and 12 months postoperatively. RESULTS: There were significant and sustained
      improvements in points Aa, Ba and C. Positive stress test was observed in 29.8%
      preoperatively and decreased to 1.9% after 12 months. There was no significant
      impact in sexual symptoms. Mesh exposure was noted in 5.7% of patients.
      CONCLUSIONS: Monoprosthesis with combined prepubic and transobturator arms
      presented high success rates for AVP repair and simultaneous SUI treatment. It
      has also been shown to be safe and appears to preserve sexual function.

PMID- 21720914
TI  - Paired opposing leukocyte receptors recognizing rapidly evolving ligands are
      subject to homogenization of their ligand binding domains.
AB  - Some leukocyte receptors come in groups of two or more where the partners share
      ligand(s) but transmit opposite signals. Some of the ligands, such as MHC class
      I, are fast evolving, raising the problem of how paired opposing receptors manage
      to change in step with respect to ligand binding properties and at the same time
      conserve opposite signaling functions. An example is the KLRC (NKG2) family,
      where opposing variants have been conserved in both rodents and primates.
      Phylogenetic analyses of the KLRC receptors within and between the two orders
      show that the opposing partners have been subject to post-speciation gene
      homogenization restricted mainly to the parts of the genes that encode the ligand
      binding domains. Concerted evolution similarly restricted is demonstrated also
      for the KLRI, KLRB (NKR-P1), KLRA (Ly49), and PIR receptor families. We propose
      the term merohomogenization for this phenomenon and discuss its significance for
      the evolution of immune receptors.

PMID- 21720915
TI  - Interaction of a functionalized complex of the flavonoid hesperetin with the AhR
      pathway and CYP1A1 expression: involvement in its protective effects against
      benzo[a]pyrene-induced oxidative stress in human skin.
AB  - Skin cancer pathogenesis is partially associated to the oxidative stress
      conditions induced by environmentally carcinogens such as benzo[a]pyrene (BaP).
      The protective effects against BaP-induced oxidative stress of the flavonoid
      hesperetin as a complex with the 2-hydroxypropyl-beta-cyclodextrin (HE/HP-beta
      CyD) have been evaluated using an ex vivo human skin model. Human healthy skin
      has been pre-treated with the functionalized complex HE/HP-beta-CyD (0.5-50 MUM)
      before BaP (5 MUM) application simulating occupational and environmental
      exposure. Oxidative stress was evaluated in terms of 3-(4, 5-dimethylthiazol-2
      yl)-2, 5-dipheyltetrazolium bromide reduction, protein peroxidation and reactive
      oxygen species (ROS) formation. Additionally, it has been investigated whether
      the potential protective effects of HE/HP-beta-CyD may be correlated to the
      interaction with aryl hydrocarbon receptor (AhR) pathway. A significant
      protection by HE/HP-beta-CyD against the BaP-induced increase in ROS and carbonyl
      compound production, as well as reduction in tissue viability, has been observed
      (p<0.001). Results obtained showed that HE/HP-beta-CyD was also able to reduce
      BaP-induced AhR and CYP1A1 protein expression (p<0.001). Experimental evidences
      provided from this study suggest significant preventive properties of HE/HP-beta
      CyD in the toxicity caused by environmental carcinogens such as PAHs.

PMID- 21720916
TI  - Occult mucin secreting adenocarcinoma of gall bladder with metastasis to urinary
      bladder.
AB  - Mucin secreting adenocarcinoma of the gall bladder is rare. Although it has
      propensity to metastasise, urinary metastasis is extremely unusual. We report a
      case with mucin secreting adenocarcinoma of the gall bladder with metastasis to
      the urinary bladder. To the best of our knowledge, this is the first case of its
      kind in the literature.

PMID- 21720917
TI  - The partner-specific sexual liking and sexual wanting scale: psychometric
      properties.
AB  - Inspired by research showing that wanting (one's motivation to engage in an
      activity) often diverges from liking (one's enjoyment of the activity), this
      article details the development and validation of a new measure to examine the
      distinction between sexual wanting and liking within a relationship: the partner
      specific sexual liking and wanting (PSSLW) scale. In Study 1, participants (N =
      1145; 63% female) completed items intended to measure PSSLW. Factor analysis
      supported a 15-item two-factor solution that explained 64.7% of the total
      variance. The partner-specific sexual liking (PSSL) subscale (Cronbach's alpha =
      .93) and the partner-specific sexual wanting (PSSW) subscale (Cronbach's alpha =
      .87) showed good internal validity. Test-retest reliability on a subsample (n =
      30) was high (Pearson's r = .75). In Study 2, participants (N = 67; 71.6% female)
      completed the PSSLW scale and additional measures of satisfaction and desire.
      Both scales displayed satisfactory discriminant and convergent validity. In Study
      3, participants (N = 2589; 45.3% female) completed the PSSLW scale and answered
      questions about sexual behavior within their relationships. The two subscales
      were distinctly correlated with measures of self-reported behavior. Moreover,
      confirmatory factor analysis (CFA) yielded a good-fit two-factor model, where the
      Comparative Fit Index (CFI) = .97, Tucker Lewis Index (TLI) = .96, and root mean
      square error of approximation (RMSEA) = .06. Data from these three studies
      suggested that PSSLW were distinct, measurable, and valid constructs that have
      the potential to enrich future studies of sexual experience and behavior within
      sexual partnerships.

PMID- 21720918
TI  - CCN1 contributes to skin connective tissue aging by inducing age-associated
      secretory phenotype in human skin dermal fibroblasts.
AB  - Dermal connective tissue collagen is the major structural protein in skin.
      Fibroblasts within the dermis are largely responsible for collagen production and
      turnover. We have previously reported that dermal fibroblasts, in aged human skin
      in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates
      collagen homeostasis by suppressing collagen synthesis and increasing collagen
      degradation (Quan et al. Am J Pathol 169:482-90, 2006, J Invest Dermatol 130:1697
      706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters
      collagen homeostasis by promoting expression of specific secreted proteins, which
      include matrix metalloproteinases and proinflammatory cytokines. We also find
      that CCN1-induced secretory proteins are elevated in aged human skin in vivo. We
      propose that CCN1 induces an "Age-Associated Secretory Phenotype", in dermal
      fibroblasts, which mediates collagen reduction and fragmentation in aged human
      skin.

PMID- 21720920
TI  - The British Lexicon Project: lexical decision data for 28,730 monosyllabic and
      disyllabic English words.
AB  - We present a new database of lexical decision times for English words and
      nonwords, for which two groups of British participants each responded to 14,365
      monosyllabic and disyllabic words and the same number of nonwords for a total
      duration of 16 h (divided over multiple sessions). This database, called the
      British Lexicon Project (BLP), fills an important gap between the Dutch Lexicon
      Project (DLP; Keuleers, Diependaele, & Brysbaert, Frontiers in Language Sciences.
      Psychology, 1, 174, 2010) and the English Lexicon Project (ELP; Balota et al.,
      2007), because it applies the repeated measures design of the DLP to the English
      language. The high correlation between the BLP and ELP data indicates that a high
      percentage of variance in lexical decision data sets is systematic variance,
      rather than noise, and that the results of megastudies are rather robust with
      respect to the selection and presentation of the stimuli. Because of its design,
      the BLP makes the same analyses possible as the DLP, offering researchers with a
      new interesting data set of word-processing times for mixed effects analyses and
      mathematical modeling. The BLP data are available at http://crr.ugent.be/blp and
      as Electronic Supplementary Materials.

PMID- 21720919
TI  - Down-regulation of free riboflavin content induces hydrogen peroxide and a
      pathogen defense in Arabidopsis.
AB  - Riboflavin mediates many bioprocesses associated with the generation of hydrogen
      peroxide (H2O2), a cellular signal that regulates defense responses in plants.
      Although plants can synthesize riboflavin, the levels vary widely in different
      organs and during different stages of development, indicating that changes in
      riboflavin levels may have physiological effects. Here, we show that changing
      riboflavin content affects H2O2 accumulation and a pathogen defense in
      Arabidopsis thaliana. Leaf content of free riboflavin was modulated by ectopic
      expression of the turtle gene encoding riboflavin-binding protein (RfBP). The
      RfBP-expressing Arabidopsis thaliana (REAT) plants produced the RfBP protein that
      possessed riboflavin-binding activity. Compared with the wild-type plant, several
      tested REAT lines had >70% less flavins of free form. This change accompanied an
      elevation in the level of H2O2 and an enhancement of plant resistance to a
      bacterial pathogen. All the observed REAT characters were eliminated due to RfBP
      silencing (RfBPi) under REAT background. When an H2O2 scavenger was applied, H2O2
      level declined in all the plants, and REAT no longer exhibited the phenotype of
      resistance enhancement. However, treatment with an NADPH oxidase inhibitor
      diminished H2O2 content and pathogen defense in wild-type and RfBPi but not in
      REAT. Our results suggest that the intrinsic down-regulation of free flavins is
      responsible for NADPH oxidase-independent H2O2 accumulation and the pathogen
      defense.

PMID- 21720922
TI  - Culture and maintenance of taste cells in vitro.

PMID- 21720921
TI  - Use of antifungal agents in pediatric and adult high-risk areas.
AB  - The purpose of this investigation was to describe the characteristics of the use
      of systemic antifungal agents (AFAs) and to evaluate their appropriateness of
      use. A prospective drug-utilisation study was conducted in intensive-care areas:
      haematology-oncology services and transplant units. Data were collected in three
      periods over 9 months. The required sample size was determined to be 113 patients
      (margin of error +/-7%, 95% confidence interval [CI]), assuming a variability of
      50%. Two different investigator groups evaluated the appropriateness of use
      separately; Cohen's Kappa index was used to calculate the degree of agreement
      between groups. A total of 114 patients we included, of which 62 (54.4%) were
      children. A total of 150 prescriptions were administered; fluconazole was the
      most frequently prescribed (38%), followed by liposomal amphotericin B (22.7%)
      and caspofungin (18.7%). The indications were: (1) pre-emptive treatment of
      Candida in non-neutropaenic critically ill patients (35.1%), (2) treatment of
      systemic fungal infection (24.6%), (3) prophylaxis for systemic fungal infection
      (SFI) in immunocompromised patients (16.7%), (4) prophylaxis of SFI in transplant
      recipients (12.3%), (5) prophylaxis of SFI in preterm infants (5.3%), (6)
      treatment of SFI in neonates (6.1%). The Kappa index showed a substantial
      agreement (Kappa = 0.73). The indications were considered to be inappropriate in
      71 (47.3%) episodes. The indications or dosages were inappropriate in 79 cases
      (52.7%). The indications, dosages or duration of treatment were inappropriate in
      83 cases (55.3%). We conclude that AFAs are prescribed for a significant number
      of inappropriate indications.

PMID- 21720923
TI  - Oral low-dose tacrolimus therapy for refractory hemophagocytic syndrome
      associated with systemic lupus erythematosus.
AB  - Hemophagocytic syndrome (HPS) is an unusual disorder associated with systemic
      lupus erythematosus (SLE). A 64-year-old woman was admitted because of fever and
      urticarial vasculitis. Laboratory data revealed pancytopenia and immunological
      abnormalities, suggesting elevated disease activity. Prednisolone monotherapy
      failed to improve the pancytopenia despite the amelioration of other clinical
      findings. Because her condition was suggestive of HPS, tacrolimus at 2-3 mg/day
      was added to the prednisolone regimen. Eventually, the pancytopenia improved and
      prednisolone could be effectively tapered. Tacrolimus could be an additional or
      alternative modality for treating refractory HPS.

PMID- 21720924
TI  - Clostridium difficile colitis: factors associated with outcome and assessment of
      mortality at a national level.
AB  - BACKGROUND: Previous descriptions of Clostridium difficile colitis (CDC)
      epidemics may overestimate cost and mortality of CDC. METHODS: An analysis of the
      2007 Nationwide Inpatient Sample was performed. Patients with CDC (N = 41,207)
      were compared to a propensity score-matched cohort of patients without CDC.
      RESULTS: Average length of stay was longer for CDC patients by 5 days (p <
      0.001). Mortality was higher for the CDC cohort (9.4% vs. 8.6%; p < 0.001) though
      the absolute difference was small. Mean hospital costs were 56% higher for CDC
      patients (p < 0.001). Higher odds of death with CDC were associated with small
      hospitals and self-pay patients. Chronic renal failure and diabetes were
      associated with lower hospital costs and lower odds of death in the CDC cohort.
      CONCLUSIONS: CDC is not as deadly of a disease as it may be perceived to be at
      larger hospitals, and mortality was actually unaffected by certain serious
      comorbidities. CDC is expensive due to a longer hospital stay.

PMID- 21720925
TI  - Bleeding and thromboembolic outcomes for patients on oral anticoagulation
      undergoing elective colon and rectal abdominal operations.
AB  - PURPOSE: Patients on chronic oral anticoagulation can be challenging to manage in
      the perioperative period. METHODS: Review of patients on warfarin undergoing
      elective abdominal colon and rectal operations at a single institution from 2000
      to 2006. RESULTS: One forty-six patients underwent 165 abdominal procedures. Mean
      (+/-SEM) age was 67 +/- 1 years; 59% of patients were men. Median estimated blood
      loss was 200 ml, and 19% received intraoperative blood products while 19% of
      patients received a postoperative transfusion. Sixteen patients (10%) experienced
      bleeding complications (three requiring reoperation). No risk factors for
      bleeding were identified by multivariate analysis (MVA). Five patients (3%)
      suffered a postoperative thromboembolic event. Preoperative anticoagulation for
      cerebrovascular disease was a risk factor for thromboembolism (p = 0.03). Overall
      operative morbidity was 30% with no identifiable risk factor in MVA. Mortality
      was nil. CONCLUSION: Postoperative bleeding and thromboembolism in patients on
      chronic anticoagulation are not insignificant (10% and 3%, respectively).
      Patients on warfarin for cerebrovascular disease are at increased risk for
      thromboembolic events postoperatively and should be placed on appropriate
      prophylaxis and monitored.

PMID- 21720926
TI  - Laparoscopic and endoscopic pyloroplasty for gastroparesis results in sustained
      symptom improvement.
AB  - BACKGROUND: Gastroparesis is a chronic digestive disorder with symptoms of
      nausea, vomiting, bloating, and abdominal pain resulting in a poor quality of
      life. Surgeons are increasingly asked to treat patients with gastroparesis as
      medical options have become limited due to safety concerns of many prokinetics.
      Surgical options include gastric stimulator implantation, sub-total gastrectomy,
      and pyloroplasty. We report our experience with minimally invasive pyloroplasty
      as sole surgical treatment for adult gastroparesis. MATERIALS AND METHODS: A
      retrospective review of prospectively collected data of 28 patients who underwent
      minimally invasive pyloroplasty alone as treatment for gastroparesis from Jan
      2007 to Sept 2010. Pre- and postoperative symptom severity score (SSS), gastric
      emptying scintigraphy (GES), and medication use were reviewed. RESULTS: A
      laparoscopic Heineke-Mikulicz pyloroplasty was performed in 26 patients. A
      laparoscopic assisted, flexible trans-oral endoscopic circular stapled
      pyloroplasty was used in two patients. Prokinetic use was significantly reduced
      from 89% to 14% (p = <0.0001). The mean GES T1/2 decreased from 320 to 112 min (p
      = 0.001) and normalized in 71%. Significant improvements in the SSS were seen at
      1 month for nausea (p = <0.0001), vomiting (p = <0.0001), bloating (p = 0.0023),
      abdominal pain (p = <0.0001), and gastroesophageal reflux disease (GERD) symptoms
      (p = 0.0143). Significant improvement persisted at 3 months for nausea (p =
      <0.0001), vomiting (p = <0.0001), bloating (p = 0.0004), abdominal pain (p =
      0.0001) and GERD symptoms (p = 0.013). The average length of stay was 3.71 days.
      Overall, 83% of patients' indicated that they saw improvement at 1 month follow
      up. CONCLUSION: Minimally invasive pyloroplasty provides excellent outcomes for
      patients with gastroparesis and should be considered as a primary treatment along
      with diet and medications as it is effective and does not eliminate the option
      for additional surgical options in the future for refractory disease. With
      technological advancements, a totally endoscopic pyloroplasty may be a less
      invasive option.

PMID- 21720927
TI  - Dor against toupet fundoplication after heller myotomy. Laparoscopic technical
      improvements and endoscopic support.

PMID- 21720928
TI  - Cholecystokinin provocation HIDA test.

PMID- 21720929
TI  - Role of COX-2 in the bioactivation of methylenedianiline and in its proliferative
      effects in vascular smooth muscle cells.
AB  - 4,4'-Methylenedianiline (DAPM) is an aromatic diamine used directly in the
      production of polyurethane foams and epoxy resins, or as a precursor to MDI in
      the manufacture of some polyurethanes. In our prior experiments, we showed that
      chronic, intermittent treatment of female rats with DAPM resulted in vascular
      medial hyperplasia of pulmonary arteries. In addition, treatment of vascular
      smooth muscle cells (VSMC) in culture with DAPM increased the rates of
      proliferation in a manner that was inhibited by co-treatment with N
      acetylcysteine but was not associated with oxidative stress. We thus hypothesized
      that NAC treatment inhibited DAPM toxicity by competing for binding reactive
      intermediates formed through DAPM metabolism. Because the peroxidase enzyme
      cyclooxygenase is constitutively expressed in VSMC, and because cyclooxygenase is
      known to metabolize similar aromatic amines to electrophilic intermediates, we
      further hypothesized that DAPM-induced VSMC proliferation was dependent upon COX
      1/2-mediated bioactivation. To test this hypothesis, we treated VSMC with DAPM
      and measured cell proliferation, COX-2 expression, COX-1/2 activity, and levels
      of covalent binding. DAPM treatment resulted in a dose-dependent increase in
      proliferation that was abolished by co-treatment with the COX-2-selective
      inhibitor celecoxib. In addition, DAPM exposure increased the rates of
      proliferation in VSMC isolated from wild-type but not COX-2 (-/-) mice.
      Paradoxically, treatment with DAPM reduced the cellular production of PGE(2) and
      PGF(2alpha), but dose-dependently increased the COX-2 protein levels. Covalent
      binding of [(14)C]-DAPM to VSMC biomolecules was greater in wild-type than in COX
      2 (-/-) cells. However, covalent binding of [(14)C]-DAPM was not altered by co
      treatment with a nonselective inhibitor of cytochromes P450. These studies thus
      suggest that DAPM-induced VSMC proliferation may be due to bioactivation of DAPM,
      perhaps through the action of cyclooxygenase. The data furthermore suggest that
      DAPM's mechanism of action may possibly involve inhibition or suicide
      inactivation of COX-2. In addition, because we observed an increase in DAPM
      induced VSMC proliferation in cells isolated from female compared to male rats,
      further studies into the potential interplay between DAPM, the estrogen receptor,
      and COX-2 seem warranted.

PMID- 21720930
TI  - Effects of propofol and pentobarbital on calcium concentration in presynaptic
      boutons on a rat hippocampal neuron.
AB  - PURPOSE: Numerous reports suggest that intravenously administered (IV)
      anesthetics affect postsynaptic events in the central nervous system. However,
      there is little evidence about how general anesthetics influence the presynaptic
      processes. The level of presynaptic calcium (Ca(2+)) concentration
      ([Ca(2+)](pre)) regulates neurotransmitter release. In this study, we
      investigated the effects of anesthetic propofol IV and the barbiturate
      pentobarbital on neurotransmitter release by measuring [Ca(2+)](pre) in the
      presynaptic nerve terminals (boutons) on a dissociated single hippocampal rat
      neuron. METHODS: Sprague-Dawley rats 10-14 days old were decapitated under
      pentobarbital anesthesia, and brain slices were prepared. The hippocampal CA1
      area was touched with a fire-polished glass pipette, which vibrated horizontally,
      and neurons were dissociated, along with the attached presynaptic boutons. The
      presynaptic boutons were visualized under a confocal laser-scanning microscope
      after staining with FM1-43 dye, and [Ca(2+)](pre) was measured with acetoxymethyl
      ester of fluo-3 (fluo-3 AM). RESULTS: High potassium (K(+)) (15-90 mM) increased
      the [Ca(2+)](pre) in the Ca(2+)-containing solution in a concentration-dependent
      manner. Whereas propofol (10 MUM) and pentobarbital (300 MUM) suppressed the high
      K(+) (60 mM)-induced increase in [Ca(2+)](pre) in the boutons attached to the
      dendrite, they did not affect [Ca(2+)](pre) in the boutons attached to the soma
      or dendrite base. As a large majority of excitatory synapses are located on
      dendritic spines, these agents may affect Ca(2+) mobilization in the excitatory
      presynaptic boutons. CONCLUSIONS: Propofol and pentobarbital may affect
      neurotransmitter release from the excitatory presynaptic nerve terminals due to
      inhibition of increase in [Ca(2+)](pre).

PMID- 21720931
TI  - Changes in the composition of triacylglycerols in the fat bodies of bumblebee
      males during their lifetime.
AB  - The age-dependent changes in the composition of triacylglycerols (TAG) in the fat
      bodies of bumblebee males were studied using HPLC/MS. Two related species (Bombus
      terrestris and B. lucorum) were compared, with the age of the males being 0-30
      days. The total amount of TAG in B. lucorum was about 2.7 times higher than that
      in B. terrestris for all of the ages studied. One to three-day-old males had the
      highest content of TAG in their fat bodies (1.6-2.3 mg/individual in B.
      terrestris and 3.8-4.2 mg/individual in B. lucorum). The analytical data show
      different patterns in both species. The qualitative composition of fatty acids in
      TAG was similar, but the mean relative abundance between B. terrestris and B.
      lucorum differed: 14:0, 7 and 14%; 16:0, 20 and 44%; 18:3, 62 and 23%; 18:1, 3
      and 8%, respectively (the data is based on a GC/MS integration). A statistical
      evaluation of the dynamic changes in the TAG composition revealed that in B.
      terrestris different age classes were well separated according to their TAG
      composition while in B. lucorum the TAG did not change substantially during the
      male's life. The TAG analyses provide more precise information on the differences
      between the classes studied than the FA composition alone.

PMID- 21720932
TI  - Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive
      processing in multiple sclerosis.
AB  - Information-processing speed (IPS) slowing is a primary cognitive deficit in
      multiple sclerosis (MS). Basal ganglia, thalamus and neocortex are thought to
      have a key role for efficient information-processing, yet the specific relative
      contribution of these structures for MS-related IPS impairment is poorly
      understood. To determine if basal ganglia and thalamus atrophy independently
      contribute to visual and auditory IPS impairment in MS, after controlling for the
      influence of neocortical volume, we enrolled 86 consecutive MS patients and 25
      normal controls undergoing 3T brain MRI and neuropsychological testing. Using
      Sienax and FIRST software, neocortical and deep gray matter (DGM) volumes were
      calculated. Neuropsychological testing contributed measures of auditory and
      visual IPS using the Paced Auditory Serial Addition Test (PASAT) and the Symbol
      Digit Modalities Test (SDMT), respectively. MS patients exhibited significantly
      slower IPS relative to controls and showed reduction in neocortex, caudate,
      putamen, globus pallidus, thalamus and nucleus accumbens volume. SDMT and PASAT
      were significantly correlated with all DGM regions. These effects were mitigated
      by controlling for the effects of neocortical volume, but all DGM volumes
      remained significantly correlated with SDMT, putamen (r = 0.409, p < 0.001) and
      thalamus (r = 0.362, p < 0.001) having the strongest effects, whereas for PASAT,
      the correlation was significant for putamen (r = 0.313, p < 0.01) but not for
      thalamus. We confirm the significant role of thalamus atrophy in MS-related IPS
      slowing and find that putamen atrophy is also a significant contributor to this
      disorder. These DGM structures have independent, significant roles, after
      controlling for the influence of neocortex atrophy.

PMID- 21720933
TI  - Genetic differentiation of Colletotrichum gloeosporioides and C. truncatum
      associated with Anthracnose disease of papaya (Carica papaya L.) and bell pepper
      (Capsium annuum L.) based on ITS PCR-RFLP fingerprinting.
AB  - Members of the genus Colletotrichum include some of the most economically
      important fungal pathogens in the world. Accurate diagnosis is critical to
      devising disease management strategies. Two species, Colletotrichum
      gloeosporioides and C. truncatum, are responsible for anthracnose disease in
      papaya (Carica papaya L.) and bell pepper (Capsicum annuum L.) in Trinidad. The
      ITS1-5.8S-ITS2 region of 48 Colletotrichum isolates was sequenced, and the ITS
      PCR products were analyzed by PCR-RFLP analysis. Restriction site polymorphisms
      generated from 11 restriction enzymes enabled the identification of specific
      enzymes that were successful in distinguishing between C. gloeosporioides and C.
      truncatum isolates. Species-specific restriction fragment length polymorphisms
      generated by the enzymes AluI, HaeIII, PvuII, RsaI, and Sau3A were used to
      consistently resolve C. gloeosporioides and C. truncatum isolates from papaya.
      AluI, ApaI, PvuII, RsaI, and SmaI reliably separated isolates of C.
      gloeosporioides and C. truncatum from bell pepper. PvuII, RsaI, and Sau3A were
      also capable of distinguishing among the C. gloeosporioides isolates from papaya
      based on the different restriction patterns that were obtained as a result of
      intra-specific variation in restriction enzyme recognition sites in the ITS1-5.8S
      ITS2 rDNA region. Of all the isolates tested, C. gloeosporioides from papaya also
      had the highest number of PCR-RFLP haplotypes. Cluster analysis of sequence and
      PCR-RFLP data demonstrated that all C. gloeosporioides and C. truncatum isolates
      clustered separately into species-specific clades regardless of host species.
      Phylograms also revealed consistent topologies which suggested that the genetic
      distances for PCR-RFLP-generated data were comparable to that of ITS sequence
      data. ITS PCR-RFLP fingerprinting is a rapid and reliable method to identify and
      differentiate between Colletotrichum species.

PMID- 21720934
TI  - Decreased length of stay after TKA is not associated with increased readmission
      rates in a national Medicare sample.
AB  - BACKGROUND: There is a trend toward decreasing length of hospital stay (LOS)
      after TKA although it is unclear whether this trend is detrimental to the overall
      postoperative course. Such information is important for future decisions related
      to cost containment. QUESTIONS/PURPOSES: We determined whether decreases in LOS
      after TKA are associated with increases in readmission rates. PATIENTS AND
      METHODS: We retrospectively reviewed the rates and reasons for readmission and
      LOS for 4057 Medicare TKA patients from 2002 to 2007. We abstracted data from the
      Medicare Patient Safety Monitoring System. Hierarchical generalized linear
      modeling was used to assess the odds of changing readmission rates and LOS over
      time, controlling for changes in patient demographic and clinical variables.
      RESULTS: The overall readmission rate in the 30 days after discharge was 228/4057
      (5.6%). The 10 most common reasons for readmission were congestive heart failure
      (20.4%), chronic ischemic heart disease (13.9%), cardiac dysrhythmias (12.5%),
      pneumonia (10.8%), osteoarthrosis (9.4%), general symptoms (7.4%), acute
      myocardial infarction (7.0%), care involving other specified rehabilitation
      procedure (6.3%), diabetes mellitus (6.3%), and disorders of fluid, electrolyte,
      and acid-base balance (5.9%); the top 10 causes did not include venous
      thromboembolism syndromes. We found no difference in the readmission rate between
      the periods 2002-2004 (5.5%) and 2005-2007 (5.8%) but a reduction in LOS between
      the periods 2002-2004 (4.1 +/- 2.0 days) and 2005-2007 (3.8 +/- 1.7 days).
      CONCLUSIONS: The most common causes for readmission were cardiac-related. A
      reduction in LOS was not associated with an increase in the readmission rate in
      this sample. Optimization of cardiac status before discharge and routine primary
      care physician followup may lead to lower readmission rates.

PMID- 21720935
TI  - Oxidative stress, obstructive sleep apnea and cardiovascular disease.

PMID- 21720936
TI  - Clinical presentation of shift workers to a sleep clinic.
AB  - PURPOSE: The purpose of this study was to assess the relationship between shift
      work (SW) history and symptom severity in a sleep clinic population. METHODS: A
      retrospective chart review of 1,275 employed adult patients referred to a sleep
      disorders clinic was performed. Patients were categorized as working day shift,
      fixed evening or night shift, or rotating shifts. Sleep-related symptoms were
      assessed across three domains-sleepiness, insomnia, and apnea-related symptoms.
      RESULTS: The distribution of work shift was 69% day shift, 8% fixed evening or
      night shift, and 23% rotating shifts. In general, sleepiness and insomnia
      symptoms were greatest in fixed shift workers. In analyses adjusted for age, sex,
      education, race, BMI, habitual sleep duration, marital status, education level,
      alcohol intake, and smoking history, fixed shift workers were 4.8 times (95% CI,
      1.9-12.5) more likely to report sleep onset difficulties, 3.3 times (95% CI, 1.2
      9.1) more likely to report excessive caffeine intake, and 1.8 times (95% CI, 1.1
      3.0) more likely to report drowsy driving as compared to day shift workers. In
      contrast, rotating shift workers reported more difficulty with sleep onset (OR
      2.7; 95% CI, 1.3-5.6) relative to day shift workers. No relationship between work
      shift and apnea-related symptoms was identified. CONCLUSIONS: Among patients
      referred to a sleep disorders clinic, shift workers and in particular fixed shift
      workers have greater difficulties with sleep onset, drowsy driving, and excessive
      caffeine intake. Given the presence of effective treatments for SW-related sleep
      symptoms, these findings suggest an underutilization of sleep medicine
      specialists for the care of patients with symptoms related to SW.

PMID- 21720937
TI  - Educating cancer prevention researchers in emerging biobehavioral models: lessons
      learned.
AB  - To increase the adoption of transdisciplinary research methods among future
      cancer prevention investigators, faculty members from The University of Texas MD
      Anderson Cancer Center developed a graduate-level course in biobehavioral methods
      in cancer prevention research. Two instructors paired by topic and area of
      expertise offered an hour-long lecture-based seminar every week for 15 weeks
      during the spring semester of 2010. Students and presenters both evaluated the
      overall course content and delivery method, as well as each session. A total of
      11 students and 22 presenters participated in the course. In each class session,
      one presenter was from a behavioral science background,and the other was from a
      biological sciences background. Both presenters and students expressed overall
      satisfaction with the content and format of the course. The presentation of
      topics from a transdisciplinary perspective and interaction with presenters from
      both biological and behavioral sciences are valuable and can help junior
      researchers prepare to meet the emerging challenges in cancer prevention
      research.

PMID- 21720938
TI  - The clinical features and surgical outcomes of patients with intramedullary
      spinal cord cavernous malformations.
AB  - BACKGROUND: Cavernous malformations (CMs) are not uncommon, but most of them are
      found to be located intracranially. Intramedullary CMs are rare, accounting for
      only 3-5% of identified total central nervous system lesions. The natural history
      of intramedullary CMs and their clinical features, including the risk of
      hemorrhage from a large series, still remains unclear and needs to be elucidated.
      We review our experience with surgically treated patients with intramedullary CMs
      and discuss the clinical features and surgical outcomes. METHODS: Between March
      2004 and March 2010, a total of 21 patients with intramedullary spinal cord CMs
      were surgically treated in a single institution. Data from 21 patients were
      retrospectively analyzed. RESULTS: There were 13 females and 8 males ranging in
      age from 10 to 70 years (mean age 39.3 years). All patients harbored single
      symptomatic CM of the nervous system, and multiple lesions were not found. The
      annual retrospective hemorrhage rate was 2.18% per patient/year. All but one CM
      were completely resected, and the average follow-up period was 22.1 months (1-73
      months). Ten of the 21 patients experienced an improvement in neurological state,
      9 patients remained unchanged, and 2 patients experienced worsening of their
      conditions. CONCLUSIONS: Symptomatic intramedullary CMs should be surgically
      removed to avoid further neurological deterioration. Though there are some
      limitations due to the retrospective nature of this study and its small number of
      patients, the prognosis was found to be related to the preoperative neurological
      state and to the type of symptom presentation.

PMID- 21720940
TI  - [Comments on the article "Cutaneous side effects of the multikinase inhibitors
      sorafenib and sunitinib"].

PMID- 21720941
TI  - Prognostic impact of T2-weighted CMR imaging for cardiac amyloidosis.
AB  - OBJECTIVES: Using cardiac magnetic resonance imaging (MRI) we tested the
      diagnostic value of various markers for amyloid infiltration. METHODS: We
      performed MRI at 1.5 T in 36 consecutive patients with cardiac amyloidosis and 48
      healthy volunteers. The protocol included cine imaging, T2-weighted spin echo, T1
      weighted spin echo before and early after contrast and late gadolinium
      enhancement. We compared the frequency of abnormalities and their relation to
      mortality. RESULTS: Median follow-up was 31 months. Twenty-three patients died.
      Mean left ventricular (LV) mass was 205 +/- 70 g. LV ejection fraction (EF) was
      55 +/- 12%. T2 ratio was 1.5 +/- 0.4. 33/36 patients had pericardial and 22/36
      had pleural effusions. All but two had heterogeneous late enhancement. Surviving
      patients did not differ from those who had died with regard to gender, LV mass or
      volume. Surviving patients had a significantly higher LVEF (60.4 +/- 9.9% vs.
      51.6 +/- 11.5%; p = 0.03). The deceased patients had a lower T2 ratio than those
      who survived (1.38 +/- 0.42 vs. 1.76 +/- 0.17; p = 0.005). Low T2 was associated
      with shorter survival (Chi-squared 11.3; p < 0.001). Cox regression analysis
      confirmed T2 ratio < 1.5 as the only independent predictors for survival.
      CONCLUSION: Cardiac amyloidosis is associated with hypointense signal on T2
      weighted images. A lower T2 ratio was independently associated with shortened
      survival.

PMID- 21720942
TI  - 4D-MR flow analysis in patients after repair for tetralogy of Fallot.
AB  - OBJECTIVES: Comprehensive analysis of haemodynamics by 3D flow visualisation and
      retrospective flow quantification in patients after repair of tetralogy of Fallot
      (TOF). METHODS: Time-resolved flow-sensitive 4D MRI (spatial resolution ~ 2.5 mm,
      temporal resolution = 38.4 ms) was acquired in ten patients after repair of TOF
      and in four healthy controls. Data analysis included the evaluation of
      haemodynamics in the aorta, the pulmonary trunk (TP) and left (lPA) and right
      (rPA) pulmonary arteries by 3D blood flow visualisation using particle traces,
      and quantitative measurements of flow velocity. RESULTS: 3D visualisation of
      whole heart haemodynamics provided a comprehensive overview on flow pattern
      changes in TOF patients, mainly alterations in flow velocity, retrograde flow and
      pathological vortices. There was consistently higher blood flow in the rPA of the
      patients (rPA/lPA flow ratio: 2.6 +/- 2.5 vs. 1.1 +/- 0.1 in controls). Systolic
      peak velocity in the TP was higher in patients (1.9 m/s +/- 0.7 m/s) than
      controls (0.9 m/s +/- 0.1 m/s). CONCLUSIONS: 4D flow-sensitive MRI permits the
      comprehensive evaluation of blood flow characteristics in patients after repair
      of TOF. Altered flow patterns for different surgical techniques in the small
      patient cohort may indicate its value for patient monitoring and potentially
      identifying optimal surgical strategies.

PMID- 21720943
TI  - Intravenous flat detector CT angiography for non-invasive visualisation of
      intracranial flow diverter: technical feasibility.
AB  - OBJECTIVE: To demonstrate the feasibility of intravenous Flat Detector CT
      Angiography (FD-CTA) for visualisation of intracranial Flow Diverting Devices.
      Flow Diverting Devices are used increasingly for treatment of intracranial
      aneurysms. A close follow up is necessary because it becomes obvious that a
      significant proportion of aneurysms treated with these devices remain patent. A
      minimally invasive method is highly desirable. METHODS: In two patients treated
      with flow diverters a Flat Detector CT (FD-CT) with intravenous contrast medium
      application was performed. Post-processing was performed using commercially
      available software. RESULTS: In both patients the lumen of the device and the
      lumen of the aneurysm could be clearly evaluated. Some beam hardening artefacts
      due to the marker wires of the device were obvious. CONCLUSION: Flat Detector CT
      with intravenous contrast material application to evaluate flow-diverting devices
      seems to be feasible. Further studies are necessary to perform comparative
      evaluation of FD-CTA with angiography and other techniques like MRA or
      conventional CT angiography.

PMID- 21720944
TI  - MADS and more: transcription factors that shape the plant.
AB  - All major processes of life depend on differential gene expression, which is
      largely controlled by the activity of transcription factors (TFs). In plants many
      TFs are encoded by members of multigene families that expanded much more
      dramatically during land plant evolution than during the evolution of animals and
      fungi. Here we review typical features such as domain structure, DNA binding, and
      protein interactions of TFs from some families that have contributed to the
      development and evolution of plant-specific structures in especially important
      ways. Our survey includes the MADS-domain protein family involved in specifying
      meristem and organ identity; YABBY proteins controlling lamina outgrowth; TCP
      proteins controlling floral zygomorphy and apical dominance; and finally
      homeodomain proteins involved in stem-cell maintenance and many other processes.
      Common themes as well as interesting differences between these "molecular
      architects of plant body plans" will become apparent.

PMID- 21720945
TI  - In silico mining and PCR-based approaches to transcription factor discovery in
      non-model plants: gene discovery of the WRKY transcription factors in conifers.
AB  - WRKY transcription factors are key regulators of numerous biological processes in
      plant growth and development, as well as plant responses to abiotic and biotic
      stresses. Research on biological functions of plant WRKY genes has focused in the
      past on model plant species or species with largely characterized transcriptomes.
      However, a variety of non-model plants, such as forest conifers, are essential as
      feed, biofuel, and wood or for sustainable ecosystems. Identification of WRKY
      genes in these non-model plants is equally important for understanding the
      evolutionary and function-adaptive processes of this transcription factor family.
      Because of limited genomic information, the rarity of regulatory gene mRNAs in
      transcriptomes, and the sequence divergence to model organism genes,
      identification of transcription factors in non-model plants using methods similar
      to those generally used for model plants is difficult. This chapter describes a
      gene family discovery strategy for identification of WRKY transcription factors
      in conifers by a combination of in silico-based prediction and PCR-based
      experimental approaches. Compared to traditional cDNA library screening or EST
      sequencing at transcriptome scales, this integrated gene discovery strategy
      provides fast, simple, reliable, and specific methods to unveil the WRKY gene
      family at both genome and transcriptome levels in non-model plants.

PMID- 21720946
TI  - Isolation of plant transcription factors using a yeast one-hybrid system.
AB  - The yeast one-hybrid (Y1H) system is a powerful tool for the identification and
      isolation of cDNAs of transcription factors using promoter segments or regulatory
      elements as baits. Here we propose an adaptation of the Y1H system for
      identification and cloning of transcription factors using Matchmaker (Clontech)
      Y2H cDNA libraries. The method is a modification of the standard one-hybrid
      screening protocol, utilising a mating step to introduce the library and reporter
      constructs into the same cell. This extends the compatibility of Matchmaker cDNA
      libraries from yeast two-hybrid screens to one-hybrid screens. Libraries were
      successfully prepared from wheat, barley and maize grain, spike, leaf and root
      tissues from plants subjected to several environmental stresses. Using this
      method, we have isolated more than 50 cDNAs encoding transcriptional factors from
      several different families.

PMID- 21720947
TI  - A transposon-based activation tagging system for gene function discovery in
      Arabidopsis.
AB  - Activation tagging is a powerful strategy to find new gene functions, especially
      from genes that are redundant or show lethal knock-out phenotypes. It has been
      applied using T-DNA or transposons. En/Spm-I/dSpm engineered transposons are
      efficient activation tags in Arabidopsis. An immobilized transposase source and
      an enhancer-bearing non-autonomous element are used in combination with positive
      and negative selectable markers to generate a population of single- or low-copy,
      stable insertions. This method describes the steps required for selection of
      parental lines, generation of a population of stable insertions, and gene
      identification.

PMID- 21720948
TI  - CRES-T, an effective gene silencing system utilizing chimeric repressors.
AB  - Chimeric REpressor gene Silencing Technology (CRES-T) is a useful tool for
      functional analysis of plant transcription factors. In this system, a chimeric
      repressor that is produced by fusion of a transcription factor to the plant
      specific EAR-motif repression domain (SRDX) suppresses target genes of a
      transcription factor dominantly over the activity of endogenous and functionally
      redundant transcription factors. As a result, the transgenic plants that express
      a chimeric repressor exhibit phenotypes similar to loss-of-function of the
      alleles of the gene encoding the transcription factor. This system is simple and
      effective and can be used as a powerful tool not only for functional analysis of
      redundant transcription factors but also for the manipulation of plant traits by
      active suppression of the gene expression. Strategies for construction of the
      chimeric repressors and their expression in transgenic plants are described.
      Transient effector-reporter assays for functional analysis of transcription
      factors and detection of protein-protein interactions using the trans-repressive
      activity of SRDX repression domain are also described.

PMID- 21720949
TI  - Analysis of a transcription factor using transient assay in Arabidopsis
      protoplasts.
AB  - Regulation of gene expression by transcription factors is a fundamental mechanism
      in essentially all aspects of cellular processes. Transient expression assay of a
      reporter plasmid containing a reporter gene driven by a promoter of interest and
      an effector plasmid expressing a transcription factor has been a powerful tool
      for analyzing transcription factors. Here we present a protocol for polyethylene
      glycol (PEG)-mediated transformation of Arabidopsis protoplasts. It details
      preparation of protoplasts from Arabidopsis suspension cultured cells or leaves
      of soil-grown Arabidopsis plants and subsequent PEG-mediated transformation with
      reporter and effector plasmids. This protocol can be completed within 24 h from
      protoplast preparation to reporter assay. As an example, analysis of the membrane
      bound transcription factor AtbZIP60 and its target BiP3 promoter is shown.

PMID- 21720950
TI  - Microarray-based identification of transcription factor target genes.
AB  - Microarray analysis is widely used to identify transcriptional changes associated
      with genetic perturbation or signaling events. Here we describe its application
      in the identification of plant transcription factor target genes with emphasis on
      the design of suitable DNA constructs for controlling TF activity, the
      experimental setup, the statistical analysis of the microarray data, and the
      validation of target genes.

PMID- 21720951
TI  - Yeast protein-protein interaction assays and screens.
AB  - Most transcription factors fulfill their role in protein complexes. As a
      consequence, information about their interaction capacity sheds light on a
      protein's function and the molecular mechanism underlying this activity. The
      yeast two-hybrid GAL4 (Y2H) assay is a powerful method to unravel and identify
      the composition of protein complexes. This in vivo based system makes use of two
      functional protein domains of the GAL4 transcription factor, each fused to a
      protein of interest. Upon interaction between the two proteins under study, a
      transcriptional activator gets reconstituted and reporter genes get activated,
      allowing the yeast to grow on selective medium. In this chapter protocols are
      given for Y2H library screening, directed Y2H screening, Y2H matrix screening,
      and YnH screening involving more than two proteins.

PMID- 21720952
TI  - Mapping functional domains of transcription factors.
AB  - Transcription factors are modular in nature in all organisms. In general, they
      have a DNA binding domain, one or more transcription activation and/or repressor
      domain, and often a dimerization domain. In many cases, transcription factors
      also have other protein-protein interaction domain(s). Mapping these functional
      domains in transcription factors is critical in understanding their molecular
      function. In this chapter, protocols for mapping the DNA binding domain and the
      transcription activation domain of a bHLH class of transcription factor are
      described. In principle, these protocols can be applied to other classes of
      transcription factors for mapping their functional domains.

PMID- 21720953
TI  - Bimolecular fluorescence complementation as a tool to study interactions of
      regulatory proteins in plant protoplasts.
AB  - Protein-protein interactions are an important aspect of the gene regulation
      process. The expression of a gene in response to certain stimuli, within a
      specific cell type or at a particular developmental stage, involves a complex
      network of interactions between different regulatory proteins and the cis
      regulatory elements present in the promoter of the gene. A number of methods have
      been developed to study protein-protein interactions in vitro and in vivo in
      plant cells, one of which is bimolecular fluorescence complementation (BiFC).
      BiFC is a relatively simple technique based upon the reconstitution of a
      fluorescent protein. The interacting protein complex can be visualized directly
      in a living plant cell when two non-fluorescent fragments, of an otherwise
      fluorescent protein, are fused to proteins found within that complex. Interaction
      of tagged proteins brings the two non-fluorescent fragments into close proximity
      and reconstitutes the fluorescent protein. In addition, the subcellular location
      of an interacting protein complex in the cell can be simultaneously determined.
      Using this approach, we have successfully demonstrated a protein-protein
      interaction between a R2R3 MYB and a basic helix-loop-helix MYC transcription
      factor related to flavonoid biosynthetic pathway in tobacco protoplasts.

PMID- 21720954
TI  - Isolation of transcription factor complexes from Arabidopsis cell suspension
      cultures by tandem affinity purification.
AB  - Defining protein complexes is critical to virtually all aspects of cell biology
      because most cellular processes are regulated by stable or more dynamic protein
      interactions. Elucidation of the protein-protein interaction network around
      transcription factors is essential to fully understand their function and
      regulation. In the last decade, new technologies have emerged to study protein
      protein interactions under near-physiological conditions. We have developed a
      high-throughput tandem affinity purification (TAP)/mass spectrometry (MS)
      platform for cell suspension cultures to analyze protein complexes in Arabidopsis
      thaliana. This streamlined platform follows an integrated approach comprising
      generic Gateway-based vectors with high cloning flexibility, the fast generation
      of transgenic suspension cultures, TAP adapted for plant cells, and tandem matrix
      assisted laser desorption ionization MS for the identification of purified
      proteins. Recently, we evaluated the GS tag, originally developed to study
      mammalian protein complexes, that combines two IgG-binding domains of protein G
      with a streptavidin-binding peptide, separated by two tobacco etch virus cleavage
      sites. We found that this GS tag outperforms the traditional TAP tag in plant
      cells, regarding both specificity and complex yield. Here, we provide detailed
      protocols of the GS-based TAP platform that allowed us to characterize
      transcription factor complexes involved in signaling in response to the plant
      phytohormone jasmonate.

PMID- 21720955
TI  - Assaying transcription factor stability.
AB  - Similar to the activities of transcription factors (TFs) in other eukaryotes,
      activities of many plant TFs are determined via regulated proteolysis by the
      ubiquitin/26S proteasome system. Thus, to fully understand the function of a TF,
      it is important to determine the fate of the active TF protein and unravel the
      environmental and intrinsic signals that control its total cellular level. Here
      we describe how to determine whether a TF of interest is targeted to the 26S
      proteasome for degradation. The given method combines analyses of the effects of
      translational inhibition and the inhibition of proteasome activity. An important
      requirement for these experiments is to monitor in parallel the effects of
      translational and proteasomal inhibition on the abundance of the TF and (1) on
      ubiquitin, which becomes rapidly depleted upon translational inhibition (2), on
      polyubiquitinated proteins, which accumulate upon successful inhibition of the
      26S proteasome, and (3) on glutamine synthase, a very stable protein that is used
      as a general metabolic control. The method described here can be used to test TF
      stability under a variety of conditions and in different genetic backgrounds.

PMID- 21720956
TI  - How to assess the intercellular trafficking of transcription factors.
AB  - Non-cell-autonomous (NCA) control of plant development is an emerging field.
      Transcription factors (TFs) are the most important plant proteins involved in
      development and cell fate determination. In plants specialized intercellular
      symplastic channels, called plasmodesmata (PD), facilitate and regulate the NCA
      action of TFs. NCA-TFs move from cell to cell either selectively or non
      selectively depending upon the specific interactions with PD or the pathway
      proteins. Here we describe different approaches to establish the role of TFs in
      NCA control of its function and the characteristic movement behavior.

PMID- 21720957
TI  - SELEX (Systematic Evolution of Ligands by EXponential Enrichment), as a powerful
      tool for deciphering the protein-DNA interaction space.
AB  - DNA-binding proteins, including transcription factors, play essential roles in
      many biological processes. The identification of the DNA sequences to which these
      proteins bind is a first, yet still challenging, step for determining their
      functions. SELEX provides an excellent tool for deciphering protein DNA-binding
      sequence specificity, and it has been widely adopted for addressing fundamental
      biological questions. SELEX is an experimental procedure that involves the
      progressive selection, from a large combinatorial double-stranded oligonucleotide
      library, of DNA ligands with variable DNA-binding affinities and specificities by
      repeated rounds of partition and amplification. In this chapter, we describe a
      SELEX protocol that we have successfully applied to both plant and animal MYB
      transcription factors.

PMID- 21720958
TI  - Footprinting and missing nucleoside analysis of transcription factor-DNA
      complexes.
AB  - In the following chapter we describe methods and protocols to analyze the
      interaction of proteins with DNA using footprinting and related techniques based
      on the modification of DNA with either hydroxyl radicals or methylating agents.
      Footprinting, based on the protection from chemical modification of DNA through
      the specific binding of a protein, gives information about the nucleotides that
      are in close contact with the protein upon binding. The derived missing
      nucleoside and interference techniques identify nucleotides that are
      energetically important for protein binding. These methods are highly valuable to
      study in detail the interaction of a transcription factor with nucleotides on
      both strands of its target DNA sequence.

PMID- 21720959
TI  - Chromatin immunoprecipitation to verify or to identify in vivo protein-DNA
      interactions.
AB  - Chromatin immunoprecipitation (ChIP) is a valuable tool to detect the interaction
      in vivo between a DNA-associated protein and DNA fragments. Combined with
      approaches to assess gene expression in response to accumulation of a
      transcription factor, it is possible to identify direct responsive targets from
      targets that are indirectly responsive to accumulation of the transcription
      factor. ChIP may be used to confirm in vivo association of a transcriptional
      regulator with suspected target DNA fragments. ChIP may also be used to discover
      new targets, and when combined with high-throughput approaches to identify DNA
      fragments associated with a transcription factor, it may provide a tool to study
      the gene regulatory networks active during plant development and/or response to
      the environment. Furthermore, ChIP is also a powerful means to map epigenetic
      modifications within a genome.

PMID- 21720960
TI  - Visualizing and characterizing in vivo DNA-binding events and direct target genes
      of plant transcription factors.
AB  - Physical interactions between transcription factors and specific DNA sites are
      essential for gene regulation. Recent progress in genome-wide in vivo techniques,
      like chromatin immunoprecipitation followed by high-throughput sequencing (ChIP
      SEQ), enables plant researchers to generate genome-wide, high-resolution DNA
      binding maps of transcription factors. These new types of data require the use of
      advanced bioinformatic tools in order to understand the molecular mechanisms of
      functional specificity and target gene regulation by transcription factors. Here,
      we will review the use of a genome browser to visualize genome-wide DNA-binding
      maps of plant transcription factors along with other publicly available data and
      the program MEME to determine DNA sequence motifs in the bound regions. We also
      describe a tool for functional classification of target genes using GO
      annotations. Analysis of transcriptional regulatory networks requires the
      integration of multiple types of data, and this chapter aims at giving an
      overview about different bioinformatic approaches for meta-analysis and data
      integration.

PMID- 21720961
TI  - Mapping in vivo protein-DNA interactions in plants by DamID, a DNA adenine
      methylation-based method.
AB  - DamID (DNA adenine methylation identification) is an adenine methylation-based
      tagging method designed to map protein-DNA interactions in vivo. DamID, an
      alternative method to chromatin immunoprecipitation (ChIP), is based on the
      covalent linking of a "fingerprint" in the vicinity of the DNA-binding sites of
      the protein of interest. The fingerprints can be further mapped by simple
      molecular approaches. First developed by van Steensel's group in Drosophila
      melanogaster, DamID was successfully adapted to Arabidopsis thaliana, and its
      feasibility demonstrated by using the well-known yeast GAL4 transcription factor.
      The method was further used to establish a genome-wide map of the target sites of
      LHP1, a regulatory chromatin protein in A. thaliana.

PMID- 21720962
TI  - Directed evolution through DNA shuffling for the improvement and understanding of
      genes and promoters.
AB  - Unlike rational protein engineering, directed evolution provides an a priori
      approach toward the engineering of improved proteins and novel promoters. This
      minimally recursive technique builds upon small improvements by selecting and
      combining the best changes. Protein-protein/DNA interactions, catalytic
      efficiency, or resilience to inhibitors can be improved by thousands of times. By
      working within a subspace of homologous sequences, DNA shuffling recombines that
      subspace. Individuals are screened for a particular trait or two and selected for
      when they meet a set threshold. Here we explain basic principles to follow and
      provide procedures for the preparation, fragmentation, efficient size
      fractionation, and purification of parental material, as well as for the
      reassembly and rescue polymerase chain reactions (PCRs).

PMID- 21720963
TI  - Hyperbolic and kinetic models for self-organized biological aggregations and
      movement: a brief review.
AB  - We briefly review hyperbolic and kinetic models for self-organized biological
      aggregations and traffic-like movement. We begin with the simplest models
      described by an advection-reaction equation in one spatial dimension. We then
      increase the complexity of models in steps. To this end, we begin investigating
      local hyperbolic systems of conservation laws with constant velocity. Next, we
      proceed to investigate local hyperbolic systems with density-dependent speed,
      systems that consider population dynamics (i.e., birth and death processes), and
      nonlocal hyperbolic systems. We conclude by discussing kinetic models in two
      spatial dimensions and their limiting hyperbolic models. This structural approach
      allows us to discuss the complexity of the biological problems investigated, and
      the necessity for deriving complex mathematical models that would explain the
      observed spatial and spatiotemporal group patterns.

PMID- 21720964
TI  - Peritubular capillary basement membrane changes in chronic renal allograft
      rejection: Comparison of light microscopic and ultrastructural observations.
AB  - Marked peritubular capillary basement membrane (PTCBM) multilayering, the
      ultrastructural feature of chronic antibody-mediated rejection (ABMR) of kidney
      allografts, was found to correspond histologically to PTCs with thickened BMs;
      such PTCs have been suggested as a novel histological marker of chronic
      rejection. We investigated whether scoring of PTCBM thickening can substitute the
      ultrastructural search for PTCBM multilayering. The thickening was graded in PAS-
      and Jones-stained sections in 110 biopsies from recipients with a late
      dysfunction, all examined ultrastructurally for transplant capillaropathy (>=3
      PTCs with >=5 BM layers). Grade 0 indicated no thickening. Grade 1 and grade 2
      were assigned when the PTCBMs were as thick as or thicker than those of the non
      atrophic tubules, and duplication/chain-like lamination of the PTCBM was noted in
      <=3 or >=4 high-power fields, respectively. The series was enrolled in subgroups
      of those with and those without histopathological lesions of chronic rejection.
      Fifty-six biopsies displayed lesions of chronic ABMR. Transplant capillaropathy
      was demonstrated in 40 biopsies. Grade 2 thickening furnished a substantial
      interobserver concordance rate (kappa = 0.803) and correlated with the transplant
      capillaropathy. Jones staining performed somewhat better in scoring than PAS
      staining. Grade 2 thickening was verified in 35 biopsies involving chronic ABMR,
      and in one control biopsy (sensitivity 61.4%, specificity 0.98). Grade 1
      thickening was not suggestive of chronic ABMR at all. In conclusion, grade 2
      thickening can be regarded as the histopathological lesion of chronic ABMR;
      however, electron microscopy remains the gold standard in the assessment of PTCBM
      changes.

PMID- 21720965
TI  - Glucose biosensor based on titanium dioxide-multiwall carbon nanotubes-chitosan
      composite and functionalized gold nanoparticles.
AB  - In this paper, a new glucose biosensor was prepared. At first, Prussian blue (PB)
      was electrodeposited on a glassy carbon electrode (GCE) modified by titanium
      dioxide-multiwall carbon nanotubes-chitosan (TiO(2)-MWNTs-CS) composite, and then
      gold nanoparticles functionalized by poly(diallyldimethylammonium chloride) (PDDA
      Au) were adsorbed on the PB film. Finally, the negatively charged glucose oxidase
      (GOD) was self-assembled on to the positively charged PDDA-Au. The
      electrochemical performances of the modified electrodes had been studied by
      cyclic voltammetry (CV) and amperometric methods, respectively. In addition, the
      stepwise fabrication process of the as-prepared biosensor was characterized by
      scanning electron microscopy. PDDA-Au nanoparticles were characterized by
      ultraviolet-vis absorption spectroscopy and transmission electron microscopy.
      Under the optimal conditions, the as-prepared biosensor exhibited a good response
      performance to glucose with a linear range from 6 MUM to 1.2 mM with a detection
      limit of 0.1 MUM glucose (S/N = 3). In addition, this work indicated that TiO(2)
      MWNTs-CS composite and PDDA-Au nanoparticles held great potential for
      constructing biosensors.

PMID- 21720966
TI  - Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium
      compounds.
AB  - The advance in the area of synthesis and reactivity of organoselenium, as well as
      the discovery that selenium was the cause of severe intoxication episodes of
      livestock in the 1930s and the subsequent determination that selenium was an
      essential trace element in the diet for mammals, has motivated intense studies of
      the biological properties of both organic and inorganic selenium compounds. In
      this review, we shall cover a wide range of toxicological and pharmacological
      effects, in which organoselenium compounds are involved but the effects of
      inorganic compounds were not discussed in detail here. The molecular toxicity of
      inorganic selenium was described in relation to its interaction with endogenous 
      SH groups to allow a comparison with that of synthetic organoselenium compounds.
      Furthermore, in view of the recent points of epidemiological evidence that
      overexposure to selenium can facilitate the appearance of chronic degenerative
      diseases, we also briefly revised the history of selenium toxicity and physiology
      and how environmental selenium can reach inside the mammalian cells. The
      biological narrative of the element selenium, in the last century, has been
      marked by a contrast between its toxic and its beneficial effects. Thus, the
      potential therapeutic use of simple organoselenium compounds has not yet been
      sufficiently explored and, consequently, we cannot discard this class of
      compounds as promising pharmaceutical agents. In effect, the future of the
      organochalcogens as pharmacological agents will depend on more detailed
      toxicological studies in the oncoming years.

PMID- 21720967
TI  - Waist circumference and waist-to-height ratio percentiles in a nationally
      representative sample of 6-13 year old children in Switzerland.
AB  - OBJECTIVES: Central obesity, measured as waist circumference (WC), is an
      important risk factor for cardiovascular disease and diabetes already in
      children. The ratio of waist circumference to height (WHtR) is a further
      indicator for body shape. International reference values, however, do not exist
      for any of the two measures and neither do references specific to Switzerland.
      The aim of this study therefore was to develop WC and WHtR percentiles from a
      nationally representative sample of Swiss children. METHODS: In a nationally
      representative sample of 2,303 6 to 13 year old children in Switzerland weight,
      height and WC were measured and body fat % (%BF) was determined from multiple
      skinfold-thickness measurements. WC, WHtR and % BF percentiles were calculated
      using the LMS-Method of Cole and Green. RESULTS: WC increases almost linearly
      over the age range of 6 to 13 years for both boys and girls. Generally, girls
      show slightly lower WC than boys, but in the higher percentiles (85th, 90th and
      95th) they reach the same or even slightly higher values around 10 years of age.
      At the 85th percentile for boys and the 90th percentile for girls, WHtR remains
      constant over the entire age range. Above these levels the ratio increases and
      below it decreases with age. Percentiles for %BF in boys increase constantly up
      to an age of 11.5 years, after which they plateau. For girls, the plateau can be
      seen earlier, around 10.5 years, but at 12.5 years another increase begins.
      CONCLUSION: These first WC and WHtR percentiles may be useful for clinical and
      epidemiological use in Switzerland until official, validated references become
      available. An advantage in using WHtR seems to be that it is not age dependent at
      certain levels and it may therefore be possible to use a single cut-off value for
      all children.

PMID- 21720968
TI  - Age of first alcohol intoxication: association with risky drinking and other
      substance use at the age of 20.
AB  - QUESTION UNDER STUDY: To determine whether first alcohol intoxication before the
      age of 15 is associated with risky drinking patterns [Weekly Risky Drinking (WRD)
      and Binge Drinking (BD)], tobacco use, cannabis use at age 20 and other illicit
      substance use at somepoint within their lifetime. METHODS: A survey was conducted
      among 20-year-old French-speaking Swiss men attending the mandatory army
      recruitment process, using a self-administered questionnaire on alcohol and other
      substance use, as well as demographics (age, employment status, education level
      and living location). RESULTS: Of the 12'133 men attending the recruitment centre
      between January 2007 and September 2008, 9'686 were included in the study. Among
      them, 89% reported been intoxicated from alcohol at least once in the past, 11%
      reported WRD, 59% reported BD, 50% reported current tobacco use, 30% reported
      current cannabis use, and 19% reported other illicit substance use at somepoint
      within their lifetime. Subjects who reported first alcohol intoxication before
      age 15 were more likely to present current WRD (OR [95%CI]: 3.75[3.27-4.29]), BD
      (3.14[2.86-3.44]), current tobacco (3.17 [2.89-3.47]) or current cannabis use
      (3.26[2.97-3.58]), and other illicit drug use at somepoint within their lifetime
      (4.02[3.61-4.48]), than those who had a first intoxication at age 15 or older, or
      who had never been intoxicated. CONCLUSIONS: This study was consistent with the
      literature, and showed an association between age at first intoxication and
      future risky alcohol use patterns and other substance use at age 20. Although the
      results showing an association between age at first intoxication and later risky
      drinking do not necessarily imply causation, knowing the age of first
      intoxication may be useful to health care professionals in targeting adolescents
      and young adults who are at a high risk for developing alcohol and other
      substance use problems. As such, age at first intoxication may be used to
      identify vulnerable individuals in a clinical prevention setting.

PMID- 21720969
TI  - Impact of sleep-disordered breathing and its treatment on children with primary
      nocturnal enuresis.
AB  - OBJECTIVES: To determine the prevalence of primary nocturnal enuresis in
      children, to define the possible role of sleep-disordered breathing (SDB) related
      to adenotonsillar hypertrophy in enuresis, to explore the role of brain
      natriuretic peptide (BNP) levels in measuring the severity of SDB in enuretic
      children, and to evaluate the response to surgical interventions
      (adenotonsillectomy) in indicated enuretic patients. METHODS: Parental surveys of
      5-10 year-old children were reviewed for SDB and enuresis. Children with SDB were
      clinically and radiologically examined. Plasma BNP levels were determined in 33
      children with SDB and enuresis and in 30 otherwise healthy children of whom 15
      had enuresis. RESULTS: A total of 15.3% of the studied children had primary
      nocturnal enuresis, and 47 children with enuresis (30.7%) had SDB. There was a
      downward trend of enuresis and SDB as age increased. There appeared to be an
      association between the frequency of enuresis, snoring and adenotonsillar
      enlargement. Plasma BNP concentrations were significantly higher among enuretic
      children. All enuretic children with SDB underwent surgical intervention (33
      patients), and an improvement was observed in 29 children (87.8%). Among them, 15
      were cured completely, and 12 made a significant improvement in the initial 3
      months, but two made just a partial improvement over one year, and four did not
      show any improvement over one year follow up. All enuretic children with SDB who
      underwent surgery exhibited a significant reduction in daytime enuresis.
      CONCLUSIONS: The data suggests an association between nocturnal enuresis and
      adenotonsillar related SDB in children. Enuresis may add to the indications for
      surgical intervention in this group. Increased BNP levels may account for the
      increased prevalence of enuresis in context of SDB.

PMID- 21720970
TI  - Strengths and weaknesses of chest compression training: a preliminary
      retrospective study.
AB  - BACKGROUND: High quality chest compression is one of the key factors in
      successful resuscitation. A high standard of training is therefore decisive. We
      aimed to investigate the strengths and weaknesses of teaching chest compression
      in a study designed to highlight where targeted improvements in the quality of
      our chest compression training can and must be made. METHODS: Retrospective
      analysis of prospectively documented data with 234 participants, and recording
      and analysis of chest compression variables before and after a BLS training
      course. RESULTS: The results after the course were good for compression depth
      (94% correct), moderate for compression frequency (83% correct) and decompression
      (82% correct), unsatisfactory for hand positioning (74% correct) and poor for the
      compression/decompression ratio (32% correct). Practical instruction brought
      about improvements of between 9% and 48%. The greatest improvement was seen for
      hand positioning (48%), followed by compression depth (32%), compression rate
      (32%), and the compression/decompression ratio (20%). Training had only a slight
      effect on the degree of decompression (9%). Significant deteriorations were also
      noted after the course, for compression rate (11%) and the
      compression/decompression ratio (12%). CONCLUSIONS: Chest compression training
      showed weakness for four out of five variables. Only the end results for
      compression depth were satisfactory. The deficits observed in the training on
      chest compression were relevant and must be remedied. One possibility would be
      initial step-by-step training and assessment of each component of chest
      compression, concentrating in particular on hand positioning and
      compression/decompression ratio.

PMID- 21720971
TI  - A nation-wide initiative against venous thromboembolism.
AB  - There is a gap between knowledge and recommendations regarding venous
      thromboembolism (VTE) on the one hand and daily practice on the other. This fact
      has prompted a Swiss multidisciplinary group consisting of angiologists,
      haematologists, internists, and emergency medicine and pharmaceutical medicine
      specialists interested in VTE, the SAMEX group, to set up a series of surveys and
      studies that give useful insight into the situation in our country. Their
      projects encompassed prophylactic and therapeutic aspects of VTE, and enrolled
      over 7000 patients from five academic and 45 non-academic acute care hospitals
      and fifty-three private practices in Switzerland. This comprehensive Swiss
      Clinical Study Programme forms the largest database surveying current clinical
      patterns of VTE management in a representative sample of the Swiss patient
      population. Overall the programme shows a lack of thromboprophylaxis use in
      hospitalised at-risk medical patients, particularly in those with cancer, acute
      heart or respiratory failure and the elderly, as well as under-prescription of
      extended prophylaxis beyond hospital discharge in patients undergoing major
      cancer surgery. In regard to VTE treatment, planning of anticoagulation duration,
      administration of LMWH for cancer-associated thrombosis, and the use of
      compression therapy for prevention of post-thrombotic syndrome in patients with
      symptomatic proximal DVT require improvement. In conclusion, this programme
      highlights insufficient awareness of venous thromboembolic disease in
      Switzerland, underestimation of its burden and inconsistent application of
      international consensus statement guidelines regarding prophylaxis and treatment
      adopted by the Swiss Expert Group.

PMID- 21720972
TI  - [The importance of a developmental approach in psychiatric assessment and
      treatment of adults with intellectual disability].
AB  - INTRODUCTION: Mental disorders are 3-4 times more frequent in individuals with
      intellectual disabilities than in those without. From a developmental perspective
      the reason for this high prevalence could be, besides biological aberrations, a
      personality development with a difference between cognitive and emotional
      developmental levels. This discrepancy renders the person being highly vulnerable
      for the onset of problem behaviour and psychiatric disorders. For a proper
      insight into processes which have led to the disorder, it is necessary to
      evaluate the level of emotional development. This can be determined by the
      "schema of emotional development (SEO)" developed by A. Dosen. METHODS: By means
      of a case description the authors demonstrate the application of SEO in the
      assessment and utilization of the concept of the level of emotional development
      in clinical practice. RESULTS: The knowledge of the level of emotional
      development contributes to the explaining and understanding of the disorder, and
      also facilitates the establishment of an integrated diagnosis and the creation of
      appropriate integrated treatment strategies. Hence, temper tantrums, sleep
      patterns and mood improved in the case described. CONCLUSION: Besides
      biopsychosocial aspects, the developmental aspect, and in particular the level of
      emotional development should be taken into consideration in the diagnostic work
      up and treatment of individuals with intellectual disabilities and mental health
      problems. The data generated by the SEO may help in understanding the disorder
      and developing a treatment approach for these individuals.

PMID- 21720973
TI  - The frequency of prior antenatal corticosteroid therapy in late preterm birth
      pregnancies.
AB  - We sought to quantify how often women with late preterm birth (LPTB) receive
      antenatal corticosteroid (ACS) therapy prior to 34 weeks and to determine its
      effects on neonatal respiratory morbidity. LPTBs (34 (0)/ (7) to 36 (6)/ (7)
      weeks) over a 1-year period at a single tertiary care hospital were studied. A
      composite neonatal respiratory outcome was defined as mechanical ventilation,
      continuous positive airway pressure with fraction of inspired oxygen (F IO(2))
      >40% for >2 hours or F IO(2) >40% for >4 hours within the first 72 hours of life.
      Multivariate logistic regression analysis was used to evaluate the association
      between ACS therapy and neonatal respiratory morbidity. Over the study period,
      503 LPTBs met the study criteria and 6.8% ( N = 34) had ACS therapy <34 weeks.
      Most had exposure >7 days prior to delivery (64.7%). Almost one-half of those
      receiving prior ACS therapy delivered between 34 and 35 weeks. There was no
      difference in the rate of prior ACS therapy based on LPTB indication for
      delivery. After adjusting for confounding factors, prior ACS therapy was not
      associated with lower respiratory morbidity (odds ratio [OR] 2.0, 95% confidence
      interval [CI] 0.2 to 16.3,  P = 0.53). Advancing gestational age was the only
      variable associated with respiratory morbidity (OR 0.50, 95% CI 0.26 to .94,  P =
      0.03). In our population, prior ACS therapy was infrequent and was not associated
      with improvements in neonatal respiratory morbidity following LPTB.

PMID- 21720974
TI  - [Interdisciplinary recommendations for the treatment of metastatic renal cell
      carcinoma].
AB  - With the introduction of targeted drug therapies, a paradigm shift for the
      treatment of metastatic renal cell carcinoma has taken place. New compounds like
      sunitinib, sorafenib, bevacizumab and temsirolimus have become established as new
      therapeutic standards to replace the use of cytokines as standard therapy.
      Recently, these substances have been complemented by everolimus and pazopanib. An
      interdisciplinary consensus conference was held to discuss which criteria to
      consider when using these drugs (treatment sequence) and what questions remain
      unanswered based on the current study situation (open questions). Results from
      the 2009 conference provided the basis for the 2010 meeting. The results of the
      2010 conference are presented as short theses.

PMID- 21720975
TI  - [The effectiveness of levetiracetam in the treatment of neuropathic pain].
AB  - INTRODUCTION: Pharmacological treatment is the first that should be taken into
      account in dealing with neuropathic pain, antiepileptic drugs being one of the
      leading options. Levetiracetam is a state of the art antiepileptic drug that has
      displayed antinociceptive activity in experimental models of pain and clinical
      effectiveness as an analgesic in series of patients with neuropathic pain. AIM:
      To analyse the effectiveness of levetiracetam as an analgesic in the treatment of
      neuropathic pain by means of a systematic review of the literature. PATIENTS AND
      METHODS: The Medline/PubMed database was used in the study and the search
      criteria included three fundamental elements: levetiracetam, neuropathic pain and
      patients. The studies identified were those published before 31st January 2011.
      The selected studies were submitted to a quality analysis according to the
      Physiotherapy Evidence Database scale (0-10). RESULTS: Three series of cases, two
      open non-controlled pilot studies and four randomised clinical trials (RCT) were
      selected. Only the RCT met acceptable quality criteria. The aetiology of the
      neuropathic pain was different in each of the RCT analysed. Levetiracetam proved
      to be effective in the treatment of neuropathic pain in the studies with a low
      level of methodological quality (case series and pilot studies) and in one RCT
      aimed at patients with central neuropathic pain due to multiple sclerosis.
      CONCLUSIONS: Few clinical trials with a high level of methodological quality have
      been conducted to evaluate the effectiveness of levetiracetam in the treatment of
      neuropathic pain and most of those that have been carried out do not show any
      benefit in comparison to the use of a placebo.

PMID- 21720976
TI  - [Treatment of severe bruxism with botulinum toxin type A].
AB  - INTRODUCTION: The possible usefulness of botulinum toxin type A in the treatment
      of bruxism has not been studied exhaustively, being limited to some isolated case
      reports, two short case-series and a double-blind study involving a small number
      or patients. This article report our long-term experience in the treatment of
      bruxism with botulinum toxin type A. PATIENTS AND METHODS: The outcome of 19
      patients with severe bruxism who underwent periodical treatment with botulinum
      toxin A infiltrations in both temporal and masseter muscles, using initial doses
      of 25 IU per muscle, during a follow-up period ranging from 0.5 to 11 years, is
      described. Doses were adjusted in follow-up visits according the response degree.
      RESULTS: None of the patients reported side-effects. Final doses ranged from 25
      to 40 IU per muscle (mean: 29.7 +/- 4.9 UI), and duration of the effect from 13
      to 26 weeks (mean: 16.7 +/- 5.1 weeks). CONCLUSION: Botulinum toxin A
      infiltrations are a safe and useful treatment for patients with severe bruxism.

PMID- 21720977
TI  - [Involvement of the thalamic-cortical-striatal circuit in patients with obsessive
      compulsive disorder during an inhibitory control task with reward and punishment
      contingencies].
AB  - INTRODUCTION: Recent neuroimaging studies conducted on obsessive-compulsive
      disorder (OCD) show alterations in the fronto-thalamic-striatal circuit, which
      would give rise to an executive dysfunction. This could be the neurocognitive
      substrate underlying the main symptoms of OCD, i.e. obsessions and compulsions.
      SUBJECTS AND METHODS: Both brain activity and behavioural performance of a group
      of 13 patients with OCD were compared with a control group of 13 healthy subjects
      by means of functional magnetic resonance imaging while performing an inhibitory
      control task with reward and punishment contingencies. The effects of medication
      were also analysed. RESULTS: The intra-group analyses showed a longer reaction
      time during the go/no go condition in both groups, although there were no
      differences between the groups in the performance of the task. With regard to
      this task, significant activation of large areas of the cerebellum and the
      occipital, temporal and parietal lobes was observed in the healthy subjects. In
      comparison with the controls, the obsessive patients showed lower activation in
      the right-side frontal medial and superior gyri, the anterior cingulate cortex
      and the caudate nucleus, and greater activation in the inferior parietal
      convolution and the fusiform gyrus. The effects of medication were found in the
      frontal cortex and basal structures. CONCLUSIONS: These results agree with the
      argument claiming that the dysfunction in the corticostriatal system in OCD is
      associated to diminished brain activity in response to cognitive tasks.

PMID- 21720978
TI  - [Radiological findings in congenital anosmia: a case report].
AB  - INTRODUCTION: Hypoplasia of the olfactory tracts and bulbs is a rare cause of
      anosmia in the paediatric population. In most cases it is usually due to an
      acquired cause and in only a few is it associated to chromosomal disorders
      (Kallman's syndrome, among others). CASE REPORT: A 10-year-old boy with no
      chromosomal disorders and a family history of anosmia, who visited because of
      isolated anosmia; a magnetic resonance scan revealed bilateral hypoplasia of the
      olfactory tracts and bulbs. CONCLUSIONS: Magnetic resonance imaging allows the
      anatomy of the olfactory tract to be studied in detail and this makes it a
      valuable tool in the diagnosis of structural abnormalities in cases of olfactory
      disorders and also in the planning of treatment.

PMID- 21720979
TI  - [MicroRNAs in bipolar disorder: diagnostic and therapeutic applications].
AB  - INTRODUCTION: Bipolar disorder is a severe mental disease of unknown etiology
      that affects about 1% of the population. It is characterized by mood changes,
      alternating episodes of mania with depression. The current experimental and
      epidemiological data suggest that bipolar disorder represents a group of
      disorders with similar symptoms caused by the combination of genetic and
      environmental factors. Genetic analysis has identified several genes whose
      dysfunction might predispose to the disorder, although most of the results have
      not been confirmed in other studies. DEVELOPMENT: The aim of this review is to
      analyze the origin of bipolar disorder from a genetic perspective, with emphasis
      on miRNAs encoding genes. The response of patients to drugs such as lithium and
      valproate, and a series of data from different experimental approaches show that
      in some cases of bipolar disorder, genes encoding miRNAs might be involved. These
      non coding RNAs elements regulate gene expression and could participate in the
      development of diseases such as cancer, immune system disorders, heart disease
      and different mental and neurological disorders. CONCLUSIONS: Because the
      administration of mood stabilizers has been found to modify the expression of
      some miRNAs, this paper suggests that knowledge of the functions of these
      regulators could help to diagnose some cases of bipolar disorder identifying
      molecular markers in plasma. This methodology would also allow applying new
      strategy founded on effective therapeutic targets for personalized treatment.

PMID- 21720980
TI  - [Thalamic deep brain stimulation for refractory epilepsy].
AB  - Epilepsy is a neurological disorder that affects 1-2% of the population. Despite
      the available treatments (drug therapy, resective surgery, vagus nerve
      stimulation), there is a significant subgroup of patients that continues to have
      disabling seizures. The indications of deep brain stimulation are exponentially
      growing, and there is a wide experience with deep brain stimulation (DBS) for the
      treatment of abnormal movements. DBS for epilepsy may be a new therapy for the
      subgroup of patients that remain disabled despite other treatments. Experiments
      with animal models, and the new advances in our knowledge about the
      neurophysiological processes that govern the genesis of epilepsy, have led to the
      selection of various brain targets for stimulation. The thalamus is a fundamental
      relay centre in the corticothalamic and corticostriatal thalamocortical circuits,
      and it has been studied with this purpose. Studies on epileptic patients have
      shown various degrees of effectiveness; however, controlled studies do not permit
      definitive conclusions about the role of DBS in the treatment of epilepsy.
      Probably a better patient selection would lead to more decisive conclusions.
      Further randomised studies are needed to draw reliable conclusions and scientific
      evidence on the effectiveness of DBS for refractory epilepsy.

PMID- 21720981
TI  - [Economic evaluation of healthcare technologies: an introduction for physicians].
AB  - Economic evaluation of healthcare interventions is becoming increasingly
      important and are seen by decision makers as a useful tool on how best to
      allocate scarce resources efficiently by maximising the health of the population.
      It is therefore important that health care professionals understand the
      fundamentals of an economic analysis so that they can understand, evaluate and
      critically appraise published economic evaluations. This article presents an
      introduction to the economic analysis of health care interventions and describes
      the basic concepts of an economic evaluation. The authors introduce the concept
      of efficiency to defend the use of economic tools to guide or help decisions in
      healthcare. The article presents the cost-effectiveness plane as a useful
      instrument when presenting the results of an economic evaluation, and summarises
      the main ways on how costs and outcomes are measured. To help readers understand
      the concepts presented in this introduction, we draw on published examples of
      economic analyses undertaken in the field of stroke.

PMID- 21720983
TI  - [Carotid dissection in a child with pneumonia and empyema].

PMID- 21720984
TI  - [Frequency of fetal alcohol syndrome in institutionalized children of eastern
      European countries].

PMID- 21720985
TI  - [Nummular headache: shedding light on some concepts].

PMID- 21720986
TI  - Lymph node study leads to changes in breast cancer treatment: a subset of
      patients do not have poorer survival when fewer lymph nodes are removed.

PMID- 21720987
TI  - Screening mammography: bringing back into focus the value of a lifesaving
      intervention.

PMID- 21720988
TI  - 21-Gene recurrence scores: racial differences in testing, scores, treatment, and
      outcome.
AB  - BACKGROUND: African American (AA) women experience higher breast cancer mortality
      than white (W) women. These differences persist even among estrogen receptor (ER)
      positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in
      patients with ER-positive/lymph node-negative breast cancer according to RS score
      low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The
      high-risk group is most likely to benefit from chemotherapy, to achieve minimal
      benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically
      luminal B cancers). In the current study, the authors investigated racial
      differences in RS testing, scores, treatment, and outcome. METHODS: Tumor
      registry data from 3 Atlanta hospitals identified women who were diagnosed with
      breast cancers during 2005 through 2009. Medical record abstraction provided
      information on RS and other tumor/treatment factors. Statistical analyses used
      chi-square/exact tests and logistic regression. RESULTS: Of 2186 patients,
      including 1192 AA women and 992 W women, 853 women had stage I or II, ER
      positive/lymph node-negative disease and, thus, were eligible for RS testing (AA
      = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received
      testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed
      into the following groups according to risk: low risk (n = 133), medium risk (n =
      113), and high risk (n = 26). The mean RS did not differ by race, but risk groups
      did (low-risk group: 46.1% vs 50% for AA women and W women, respectively; high
      risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA
      race (odds ratio, 3.6) was associated independently with high risk scores.
      CONCLUSIONS: AA women were half as likely as W women to receive 21-gene RS
      testing but were 2-fold more likely to be categorized as high risk. The current
      data suggested that testing guidelines are not applied equivalently, testing bias
      may attenuate racial differences in RS, and disparate outcomes may be explained
      in part by differences in RS, although compliance and pharmacogenomics also may
      play a role.

PMID- 21720989
TI  - Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced
      urothelial cancer of the bladder.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of
      neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) on pathologic down
      staging of patients with locally advanced urothelial cancer (UC) of the bladder.
      METHODS: This was a retrospective cohort study of patients treated with radical
      cystectomy (RC) for clinical stage cT2-T4, N any, M0 bladder UC at Strong
      Memorial Hospital from 1999 to 2009. The primary exposure variable was use of
      neoadjuvant chemotherapy (GC vs none). The primary outcome was stage pT0 at RC.
      Secondary outcomes included other down-staging end points in the bladder (<pT1,
      <pT2, <pT3), nodal status, and surgical margins. Linear probability models were
      used to estimate the effect of neoadjuvant GC on tumor down-staging with
      adjustment for clinical staging variables. RESULTS: A total of 160 eligible
      patients were identified, of whom 25 were treated with neoadjuvant GC before RC
      (GC + RC) and 135 without neoadjuvant chemotherapy (RC only). Stage pT0 at
      cystectomy was found in 20% of patients in the GC + RC group and in 5% of
      patients in the RC group (adjusted risk difference [aRD] = 16%, P = .03). For
      other down-staging end points, the estimated treatment effect was as follows (all
      point estimates favoring chemotherapy): <pT1 aRD = 30% (P = .005); <pT2 aRD = 30%
      (P = .004); <pT3 aRD = 31% (P = .008); margins aRD = 8% (P = .41); nodes aRD = 4%
      (P = .74). CONCLUSIONS: Neoadjuvant GC was found to be capable of down-staging UC
      in the bladder; however, no effect on disease in nodes was seen in this study.

PMID- 21720990
TI  - Primary radiotherapy versus radical prostatectomy for high-risk prostate cancer:
      a decision analysis.
AB  - BACKGROUND: Two evidence-based therapies exist for the treatment of high-risk
      prostate cancer (PCA): external-beam radiotherapy (RT) with hormone therapy (H)
      (RT + H) and radical prostatectomy (S) with adjuvant radiotherapy (S + RT). Each
      of these strategies is associated with different rates of local control, distant
      metastasis (DM), and toxicity. By using decision analysis, the authors of this
      report compared the quality-adjusted life expectancy (QALE) between men with high
      risk PCA who received RT + H versus S + RT versus a hypothetical trimodality
      therapy (S + RT + H). METHODS: The authors developed a Markov model to describe
      lifetime health states after treatment for high-risk PCA. Probabilities and
      utilities were extrapolated from the literature. Toxicities after radiotherapy
      were based on intensity-modulated radiotherapy series, and patients were exposed
      to risks of diabetes, cardiovascular disease, and fracture for 5 years after
      completing H. Deterministic and probabilistic sensitivity analyses were performed
      to model uncertainty in outcome rates, toxicities, and utilities. RESULTS: RT + H
      resulted in a higher QALE compared with S + RT over a wide range of assumptions,
      nearly always resulting in an increase of >1 quality-adjusted life year with
      outcomes highly sensitive to the risk of increased all-cause mortality from H. S
      + RT + H typically was superior to RT + H, albeit by small margins (<0.5 quality
      adjusted life year), with results sensitive to assumptions about toxicity and
      radiotherapy efficacy. CONCLUSIONS: For men with high-risk PCA, RT + H was
      superior to S + RT, and the result was sensitive to the risk of all-cause
      mortality from H. Moreover, trimodality therapy may offer local and distant
      control benefits that lead to optimal outcomes in a meaningful population of men.

PMID- 21720991
TI  - What is the best way to treat high-risk prostate cancer?

PMID- 21720992
TI  - Radiation therapy for ductal carcinoma in situ: a decision analysis.
AB  - BACKGROUND: The benefit of adding radiation therapy after excision of ductal
      carcinoma in situ (DCIS) is widely debated. Randomized clinical trials are
      underpowered to delineate long-term outcomes after radiation. METHODS: The
      authors of this report constructed a Markov decision model to simulate the
      clinical course of DCIS in a woman aged 60 years who received treatment with
      either of 2 breast-conserving strategies: excision alone or excision plus
      radiation therapy. Sensitivity analyses were used to study the influence of risk
      of local recurrence, likelihood of invasive disease at recurrence, surgical
      choice at recurrence, and patient age at diagnosis on treatment outcomes.
      RESULTS: The addition of radiation therapy was associated with slight
      improvements in invasive disease-free and overall survival. However, radiation
      therapy decreased the chance of having both breasts intact over a patient's
      lifetime. Radiation therapy improved survival by 2.1 months for women who were
      diagnosed with DCIS at age 60 years but decreased the chance of having both
      breasts by 8.6% relative to excision alone. The differences in outcomes between
      the treatment strategies became smaller with increasing age at diagnosis.
      Sensitivity analyses revealed a greater benefit for radiation with an increased
      likelihood of invasive recurrence. The decrement in breast preservation with
      radiation therapy was mitigated by an increased likelihood of mastectomy at the
      time of recurrence or new breast cancer diagnosis. CONCLUSIONS: The current
      analysis quantified the benefits of radiation after excision of DCIS but also
      revealed that radiation therapy may increase the likelihood of eventual
      mastectomy. Therefore, the authors concluded that patient age and preferences
      should be considered when making the decision to add or forgo radiation for DCIS.

PMID- 21720993
TI  - Prospective impact of tumor grade assessment in biopsies on tumor stage and
      prognostic grouping in gastroesophageal adenocarcinoma: relevance of the seventh
      edition American Joint Committee on Cancer Staging Manual revision.
AB  - BACKGROUND: In the seventh edition of the American Joint Committee on Cancer
      (AJCC) staging system for esophageal cancer, tumor grade was introduced as an
      independent determinant of stage grouping in early stage tumors. With the
      significantly lower prognosis for poorly differentiated early stage
      adenocarcinomas, patients with these tumors may become candidates for neoadjuvant
      therapy given an accurate identification of these tumors with preoperative
      staging. The objective of the current study was to investigate the accuracy of
      preoperative histopathologic grading and the effect of preoperative grade on
      tumor stage/prognostic grouping. METHODS: Preoperative tumor grade was compared
      with postoperative tumor grade in 427 patients who underwent surgery without
      receiving neoadjuvant therapy for adenocarcinoma of the esophagus. The impact of
      preoperative tumor grade on stage/prognostic grouping was investigated. RESULTS:
      The overall accuracy of preoperative tumor grade assessment was 76% when unknown
      differentiation was regarded as well/moderately differentiated as recommended by
      the AJCC, whereas accuracy was 73% after the exclusion of tumors with unknown
      grade. In patients who have tumors classified as T1 or T2 and lymph node-negative
      (N0) (T1-T2N0) disease, 16% were assigned to a lower stage group based on
      preoperative pathology, whereas 5% were assigned to a higher stage group. In the
      T1-T2N0 group, sensitivity for detecting a poorly differentiated tumor was 0.43
      (95% confidence interval [CI], 0.30-0.56), whereas specificity was 0.94 (95% CI,
      0.90-0.98). CONCLUSIONS: With increasing use of neoadjuvant therapy, the accuracy
      of preoperative biopsy assessment has become increasingly important. In the
      current study, the accuracy of preoperative tumor grade assessment was 73%,
      leading to changes in AJCC stage/prognostic group in 21% of patients with T1-T2N0
      esophageal adenocarcinomas. The authors concluded that caution should be
      exhibited in staging patients with esophageal adenocarcinoma based on
      preoperative biopsy data.

PMID- 21720994
TI  - Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of
      venous thromboembolism in patients with multiple myeloma: limited effectiveness
      of thromboprophylaxis.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a significant but poorly understood
      complication in patients with newly diagnosed multiple myeloma (NDMM). As a
      result, most patients receive thromboprophylaxis with low molecular weight
      heparin (LMWH). The purpose of this retrospective study was to identify risk
      factors for VTE in NDMM and evaluate the effectiveness of LMWH. METHODS: A total
      of 604 patients with newly diagnosed myeloma completed 3 induction cycles with
      multiagent chemotherapy with up-front randomization to thalidomide between 1998
      and 2004. Prophylactic enoxaparin was given to thalidomide recipients beginning
      in June 2001, and 122 subjects received prophylactic epoetin alfa (EPO) as part
      of an exercise trial. The primary study endpoint was grades 3-4 VTE. RESULTS: A
      total of 72 patients (11.9%) developed VTE (mostly deep venous thrombosis), with
      a higher incidence among EPO recipients (P = .001), although only significant for
      upper extremity DVT (P = .0002). The EPO-treated patients had higher hemoglobin
      (Hb) levels throughout the study (P < .0005), although no relationship between
      higher Hb levels and increasing incidence of VTE could be shown. A history of VTE
      was a strong predictor of VTE on univariate analysis (P < .000005). Enoxaparin
      did not reduce the rate of VTE (P = .158). Logistic regression analysis
      identified thalidomide therapy (P = .001; odds ratio [OR], 2.428; 95% confidence
      interval [CI], 1.418-4.159) and prophylactic EPO (P = .002; OR, 2.488; 95% CI,
      1.432-4.324) as risk factors for VTE. Myeloma response and survival were not
      negatively affected by prophylactic EPO or VTE. CONCLUSIONS: Prophylactic EPO,
      thalidomide therapy, and VTE history, but not higher Hb levels, were found to
      increase the risk of VTE among NDMM patients receiving multiagent chemotherapy.
      This risk was not found to be reduced in this population by LMWH
      thromboprophylaxis.

PMID- 21720995
TI  - Bleeding in the patient with a malignancy: is it an acquired factor VIII
      inhibitor?
AB  - Many different factors can account for hemorrhagic complications in patients with
      malignancies. Potential etiologies include disease- or treatment-related
      impairment of bone marrow function, or trauma to highly friable and vascularized
      malignant tissues. Immune impairment may also occur in solid or hematologic
      malignancies, leading to spontaneous formation of inhibitory antibodies against
      coagulation factor VIII (FVIII). Because hemorrhage due to acquired FVIII
      inhibitors will not respond to conventional treatment algorithms for bleeding,
      failure to promptly recognize and diagnose this condition may result in undue
      morbidity and mortality. The persistence of FVIII autoantibodies in the patient
      with cancer may further complicate necessary invasive diagnostic or therapeutic
      procedures in the short term and lead to lethal bleeding in the long term.
      Oncologists must therefore maintain a high index of suspicion for this diagnosis
      as 1 of many potential causes of bleeding in patients with a malignancy.

PMID- 21720996
TI  - Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma
      reveals potential biomarkers and oncomirs.
AB  - BACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal
      carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the
      distinct presence of EBV microRNAs in serum could aid in screening endemic
      regions for NPC. A proposed network of genes targeted by these microRNAs could
      also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray
      profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated
      EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p)
      in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular)
      and serum microRNA copy numbers from the same 15 patients were correlated.
      Expression of the same microRNAs were also examined in EBV-positive cell lines
      C666 and NP460hTERT+EBV. Bioinformatic tools helped predict cellular target
      genes, which were later confirmed by gene expression analysis. RESULTS: The
      authors' high-throughput approach shows that EBV microRNAs are generally more up
      regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were
      significantly up-regulated in tumor versus their nontumor biopsies (P < .05).
      Upon successfully validating 12 selected EBV microRNAs in 15 additional paired
      NPC cases, the authors found that their distinct presence in the serum of NPC
      patients positively correlated with cellular copy numbers of EBV microRNAs.
      Further investigation of potential EBV microRNA target genes revealed inhibition
      of tumor suppressor genes (eg, PTEN) and extensive deregulation of several
      pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing
      knowledge of host-virus interaction via microRNAs may provide feasible
      explanations underlying NPC tumorigenesis along with the development of
      biomarkers for screening high-risk populations.

PMID- 21720997
TI  - Distinct clinical features and outcomes in never-smokers with nonsmall cell lung
      cancer who harbor EGFR or KRAS mutations or ALK rearrangement.
AB  - BACKGROUND: The objectives of this study were to determine the proportions of
      major oncogenic alterations and to examine survival in genotype-specific subsets
      of never-smokers with nonsmall cell lung cancer (NSCLC). METHODS: The authors
      concurrently analyzed mutations in the epidermal growth factor receptor (EGFR)
      and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes and
      investigated anaplastic lymphoma kinase (ALK) gene rearrangements in samples from
      229 never-smokers with NSCLC. ALK rearrangements were identified by fluorescent
      in situ hybridization and were confirmed by immunohistochemistry. Mutations in
      EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct
      sequencing. RESULTS: Of 229 tumors, the frequency of EGFR mutations, ALK
      rearrangements, KRAS mutations, and no mutations (wild type [WT]) in any of the 3
      genes (WT/WT/WT) was 48%, 8.3%, 3.5%, and 40.2%, respectively. All genetic
      alterations were mutually exclusive. The median progression-free survival after
      treatment with EGFR tyrosine kinase inhibitors (TKIs) was 12.8 months, 6.3
      months, 2.1 months, and 1.6 months in patients with EGFR mutations, the WT/WT/WT
      genotype, KRAS mutations, and ALK rearrangements, respectively. In a Cox
      regression model, the adjusted hazard ratio for the risk of disease progression
      after treatment with EGFR TKIs was 0.59 (95% confidence interval [CI], 0.40-0.87;
      P = .008) for patients with EGFR mutations, 4.58 (95% CI, 2.07-10.15; P < .001)
      for patients with ALK rearrangements, and 4.23 (95% CI, 1.65-10.8; P = .003) for
      patients with KRAS mutations. Overall survival also differed significantly among
      genotypes. CONCLUSIONS: To the authors' knowledge, this was the largest
      comprehensive and concurrent analysis to date of 3 major oncogenic alterations in
      a cohort of East Asian never-smokers with NSCLC. Because survival outcomes
      differed among genotypes, and drugs that target specific alterations currently
      are available, genetic profiling to identify genotype-specific subsets can lead
      to successful treatment with appropriate kinase inhibitors.

PMID- 21720998
TI  - Can radicality of surgery be safely modulated on the basis of MRI and PET/CT
      imaging in locally advanced cervical cancer patients administered preoperative
      treatment?
AB  - BACKGROUND: The goal of this study was to prospectively analyze the diagnostic
      performances of magnetic resonance imaging (MRI) and positron emission tomography
      (PET)/computed tomography (CT) in predicting pathologically assessed residual
      disease in a large, single-institution series of locally advanced cervical cancer
      (LACC) patients triaged to neoadjuvant treatments followed by radical surgery.
      METHODS: Between April 2007 and March 2010, 96 patients with histologically
      documented cervical cancer (any histology) and FIGO stage IB2-IVA were enrolled.
      MRI and PET/CT were recommended to be performed within 4-6 weeks from the end of
      treatment, and histology was the reference standard. Sensitivity, specificity,
      and accuracy were compared using the McNemar test. RESULTS: For residual disease
      in the cervix, sensitivity was higher for MRI than for PET/CT (86.1% vs 63.1%; P
      = .002), while specificity was significantly higher for PET/CT compared with MRI
      (P = .002). There was no difference in accuracy values between the 2 imaging
      modalities. For MRI analysis of lymph node groups, sensitivity, specificity, and
      accuracy were 35.7%, 95.9%, and 88.0%, respectively. Conversely, sensitivity,
      specificity, and accuracy for PET/CT were 28.6%, 97.8%, and 88.7%, respectively.
      Absence of follicular structures replaced by prevalent sclerosis and/or sinus
      histiocytosis was the most frequently documented morphological pattern in false
      positive cases. CONCLUSION: Neither MRI nor PET/CT accurately detected residual
      disease in LACC patients triaged to radical surgery after neoadjuvant treatment,
      disallowing the option of avoiding or modulating completion surgery.

PMID- 21720999
TI  - Individualizing antimetabolic treatment strategies for head and neck squamous
      cell carcinoma based on TP53 mutational status.
AB  - BACKGROUND: Mutations in the tumor protein 53 (TP53) tumor suppressor gene are
      common in head and neck squamous cell carcinoma (HNSCC) and correlate with
      radioresistance. Currently, there are no clinically available therapeutic
      approaches targeting p53 in HNSCC. In this report, the authors propose a strategy
      that uses TP53 mutational status to individualize antimetabolic strategies for
      the potentiation of radiation toxicity in HNSCC cells. METHODS: Glycolytic flux
      and mitochondrial respiration were evaluated in wild-type (wt) and mutant (mut)
      TP53 HNSCC cell lines. Sensitivity to external-beam radiation (XRT) was measured
      using a clonogenic assay. RESULTS: HNSCC cells that expressed mutTP53
      demonstrated radioresistance compared with HNSCC cells that expressed wtTP53.
      Glycolytic inhibition potentiated radiation toxicity in mutTP53-expressing, but
      not wtTP53-expressing, HNSCC cells. The relative sensitivity of mutTP53 HNSCC
      cells to glycolytic inhibition was caused by a glycolytic dependence associated
      with decreased mitochondrial complex II and IV activity. The wtTP53-expressing
      cells maintained mitochondrial reserves and were relatively insensitive to
      glycolytic inhibition. Inhibition of respiration using metformin increased
      glycolytic dependence in wtTP53-expressing cells and potentiated the effects of
      glycolyic inhibition on radiation toxicity. CONCLUSIONS: TP53 mutation in HNSCC
      cells was correlated with a metabolic shift away from mitochondrial respiration
      toward glycolysis, resulting in increased sensitivity to the potentiating effects
      of glycolytic inhibition on radiation toxicity. In contrast, wtTP53-expressing
      cells required inhibition of both mitochondrial respiration and glycolysis to
      become sensitized to radiation. Therefore, the authors concluded that TP53
      mutational status may be used as a marker of altered tumor cell metabolism to
      individualize HNSCC treatment selection of specific, targeted metabolic agents
      that can overcome cellular resistance to radiation therapy.

PMID- 21721000
TI  - Comparison of clinical schemas and morphologic features in predicting Lynch
      syndrome in mutation-positive patients with endometrial cancer encountered in the
      context of familial gastrointestinal cancer registries.
AB  - BACKGROUND: Endometrial cancer (EC) is the most common extraintestinal malignancy
      in Lynch syndrome (LS) and often is the sentinel malignancy, yet there is no
      consensus regarding LS-EC detection algorithms. In this study, the authors
      determined the efficacy of family/personal history and tumor morphology in
      predicting LS in a cohort of patients with EC who had mutation-proven LS.
      METHODS: Amsterdam II (AmII) criteria, revised Bethesda guidelines (rBG), and
      Society of Gynecologic Oncologists (SGO) clinical screening criteria were applied
      to the pedigrees of 76 patients with mutation-proven LS who had pathology-proven
      EC. When tumors were tested for microsatellite instability (MSI) phenotype status
      or mismatch-repair protein-immunohistochemical (MMR-IHC) expression, those
      results also were reviewed, and LS-associated histopathologic features were
      documented in 38 available patients. RESULTS: Of 76 patients, 36%, 58%, 71%, and
      93% would have been selected for further testing for LS by pedigree screening at
      the time of EC diagnosis with rBG, AmII, SGO 20%-to-25%, and SGO 5%-to-10%
      criteria, respectively. Ninety percent (18 of 20 tumors) of tested ECs had high
      MSI, and 96% (22 of 23 tumors) had abnormal MMR-IHC expression. At least 1 LS-EC
      morphologic feature was present in 16 of 38 tumors (42%). CONCLUSIONS: Clinical
      screening criteria had variable efficacy for the identification of LS-associated
      EC, and SGO 5%-to-10% criteria performed best. Characteristic pathologic features
      were present in a minority of patients. Although a high proportion of LS-ECs had
      the MSI phenotype and were MMR deficient, the specificity of these tests and of
      clinical screening for LS in unselected patients with EC has been poorly
      described. Prospective studies to determine the optimal combination of these
      screening modalities are required.

PMID- 21721001
TI  - Local epicardial inotropic drug delivery allows targeted pharmacologic
      intervention with preservation of myocardial loading conditions.
AB  - Local myocardial application of inotropes may allow the study of
      pharmacologically augmented central myocardial contraction in the absence of
      confounding peripheral vasodilating effects and alterations in heart loading
      conditions. Novel alginate epicardial (EC) drug releasing platforms were used to
      deliver dobutamine to the left ventricle of rats. Pressure-volume analyses
      indicated that although both local and systemic intravenous (i.v.) use of
      inotropic drugs increase stroke volume and contractility, systemic infusion does
      so through heart unloading. Conversely, EC application preserves heart load and
      systemic blood pressure. EC dobutamine increased indices of contractility with
      minimal rise in heart rate and lower reduction in systemic vascular resistance
      than i.v. infusion. Drug sampling showed that dobutamine concentration was 650
      fold higher in the anterior wall than in the inferior wall. The plasma dobutamine
      concentration with local delivery was about half as much as with systemic
      infusion. These data suggest that inotropic EC delivery has a localized effect
      and augments myocardial contraction by different mechanisms than systemic
      infusion, with far fewer side effects. These studies demonstrate a pharmacologic
      paradigm that may improve heart function without interference from effects on the
      vasculature, alterations in heart loading, and may ultimately improve the health
      of heart failure patients.

PMID- 21721002
TI  - Differences in colloidal structure of PEGylated nanomaterials dictate the
      likelihood of accelerated blood clearance.
AB  - PEGylated liposomes are known to exhibit accelerated clearance from systemic
      circulation on repeat administration (the so-called "accelerated blood clearance"
      or ABC effect); however, little is known about this effect for other PEGylated
      colloidal drug delivery systems. Furthermore, our understanding of the mechanisms
      by which the ABC effect is induced is limited. This article further addresses
      these issues by examining the impact of colloid types [polyethylene glycol (PEG)
      liposomes, PEG-micelles] of varying sizes on the appearance of the ABC effect
      when readministered 7 days after a "priming" dose. Intravenous injection of PEG
      liposomes and putative PEG-micelles induced the production of anti-PEG
      immunoglobulin (Ig) M, although decreasing the average particle size led to
      reduced IgM titres. The ABC effect was observed for PEGylated
      phospholipid/cholesterol-based liposomes 7 days after an initial "priming" dose
      of liposome; however, addition of increasing levels of PEGylated lipid to form
      micelles reduced the propensity of observation of the ABC effect, correlating
      with the reduced IgM production. The results suggest that although PEG-micelles
      may stimulate limited production of anti-PEG IgM, which leads to accelerated
      clearance of subsequently administered PEG-liposomes, PEGylated micelles
      themselves are not substrates for IgM binding and do not exhibit a similar ABC.

PMID- 21721003
TI  - Glass particles as an adjuvant: a model for adverse immunogenicity of therapeutic
      proteins.
AB  - Unwanted immune responses to parenterally administered therapeutic proteins pose
      serious safety and economic risks, but the mechanism(s) by which these responses
      are generated are unknown. We measured immune responses to aggregates of
      recombinant murine growth hormone (mGH) formed by agitation or freeze-thawing,
      two pharmaceutically relevant stresses, as well as to mGH adsorbed on microscopic
      glass or alum particles. Insoluble aggregates, even at levels below the detection
      limits of size-exclusion high-performance liquid chromatography analysis (<1%),
      induce immune responses when administered subcutaneously. Furthermore, we show
      that application of high hydrostatic pressures (200 MPa) reduces aggregate levels
      to 0.02 ng/dose and eliminates immunogenicity.

PMID- 21721004
TI  - Improved dermal delivery of FITC-BSA using a combination of passive and active
      methods.
AB  - This work presents results on the in vitro penetration of a model macromolecule
      [fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA)] through
      porcine skin, mediated with a microneedle skinroller (200-um-length needle) and
      different novel formulations. After perforating the porcine skin with a
      microneedle skinroller, the efficiency of delivering FITC-BSA via different novel
      formulations was evaluated and compared. Formulations, including l-alpha
      phosphatidylcholine (PC) liposomes, double emulsions, and double-encapsulation
      formulations were used. High-resolution cryo-scanning electron microscopy was
      used to visualize surface morphology and cross-section of perforated porcine
      skin. By the use of confocal microscopy, the penetration pathway and penetration
      depth of FITC-BSA through the perforated porcine skin under different
      formulations were analyzed. FITC-BSA was extracted from stratum corneum and
      viable skin, and analyzed by fluorimetry, indicating that there is no significant
      difference in the amount of FITC-BSA delivered to viable skin by PC-liposome
      suspension (12.90 +/- 1.25 ug/cm(2)) versus double-encapsulation formulations
      (10.47 +/- 0.80 ug/cm(2)); however, both formulations showed a significant
      increase as compared with an aqueous solution of FITC-BSA. In this work, double
      encapsulation formulations were used in dermal delivery for the first time and
      combined with microneedle skinroller treatment, the results showed a high
      efficiency in delivering macromolecules.

PMID- 21721005
TI  - Crystalline, liquid crystalline, and isotropic phases of sodium deoxycholate in
      water.
AB  - Sodium deoxycholate (NaDC) is an important example of bile salts, representing
      systems with complex phase behavior involving both crystalline and mesophase
      structures. In this study, properties of NaDC-water mixtures were evaluated as a
      function of composition and temperature via X-ray diffraction with synchrotron
      (sXRD) and laboratory radiation sources, water sorption, polarized light, hot
      stage microscopy, and freezing-point osmometry. Several phases were detected
      depending on the composition and temperature, including isotropic solution phase,
      liquid crystalline (LC) phase, crystalline hydrate, and ice. The LC phase was
      identified as hexagonal structure by sXRD, with up to 14 high-order reflections
      detected. The crystalline phase was found to be nonstoichiometric hydrate, based
      on XRD and water sorption data. The phase diagram of NaDC-water system has been
      refined based on both results of this study and other reports in literature.

PMID- 21721006
TI  - Are counterfeit or substandard anti-infective products the cause of treatment
      failure in Papua New Guinea?
AB  - Counterfeit and substandard products present a big challenge to any national plan
      or policy devised to improve public health. Poor quality drug products are
      especially a problem in lower income countries where product information and drug
      regulation enforcement are scant or absent. The primary aim of the present study
      was to evaluate the quality of amodiaquine and amoxicillin formulations sold in
      Papua New Guinea (PNG) and to detect the presence of counterfeit or substandard
      drugs in circulation, if any. Fourteen samples, collected from five registered
      pharmacies in Port Moresby, PNG, were subjected to visual inspection, quality
      control tests, and verification of product authenticity. The quality control
      tests included weight variation, content uniformity, thin layer chromatography,
      and dissolution. None of the products complied with all of the evaluation
      criteria. Two products, one of which was purportedly distributed by a company
      which proved to be nonexistent, contained no detectable amodiaquine. The present
      study confirms that counterfeit and substandard amodiaquine and amoxicillin
      products are finding their way into the distribution chain in Port Moresby, PNG.
      This quality problem with anti-infective products is of great concern, as it not
      only exposes patients to poor quality products but also fosters the development
      of resistant bacterial strains.

PMID- 21721007
TI  - Poor oral bioavailability of a promising anticancer agent andrographolide is due
      to extensive metabolism and efflux by P-glycoprotein.
AB  - Andrographolide (AP), isolated from Andrographis paniculata (Burm. F.) Nees, is
      an anticancer agent with significant clinical potential. This study determined
      its oral bioavailability and how intestinal disposition affects its
      bioavailability. Pharmacokinetics was evaluated in rats. Intestinal disposition
      was determined using a single-pass rat intestinal perfusion model and the
      cultured Caco-2 cells and Madin-Darby canine kidney II cells over expressing
      human P-gp (MDR1-MDCKII). Absolute bioavailability of AP was 2.67%. In the
      duodenum and jejunum, AP was rapidly metabolized to a sulfonate, identified as 14
      deoxy-12-sulfo- andrographolide. AP was also rapidly metabolized by liver S9
      fraction and in blank perfusates collected from duodenum and jejunum. The
      apparent permeability (P(app) ) of AP from basolateral (B) to apical (A) (4.94 *
      10 cm/s) in the Caco-2 model was four times higher than the P(app) from A to B
      (1.14 * 10(-5) cm/s). Moreover, AP was significantly more permeable in the B to A
      direction than the opposite direction in MDR1-MDCKII cells. In the perfusion
      model, the effective permeability (P*(eff) ) for AP was highest in the duodenum,
      followed by jejunum, and then ileum and colon. In the ileum and colon, the
      P*(eff) for AP was significantly increased by verapamil, a P-glycoprotein (P-gp)
      inhibitor. AP has poor oral bioavailability because of its rapid
      biotransformation and efflux by P-gp.

PMID- 21721008
TI  - Results of isolated lower limb perfusion for loco-regional advanced/recurrent
      melanoma using borderline true hyperthermia plus additional bolus of melphalan. A
      critical analysis of homogeneous cases.
AB  - BACKGROUND AND OBJECTIVE: This study was conducted to assess the safety and
      efficacy of our modified ILP treatment with borderline true hyperthermia and high
      melphalan concentration in stage III lower limb melanoma. METHODS: Between March
      1990 and December 2006, 91 consecutive patients were given ILP treatment. Forty
      three patients were treated with double L-PAM bolus combined with D-actinomicin;
      48 patients were treated with additional L-PAM bolus alone. RESULTS: The mean
      follow-up period is 68.5 months. The acute regional toxicity occurred with grade
      II (54%), III (38%), IV (2.1%). The systemic toxic effects were present with
      transitory hematological disorders. Complete response (CR) rate was observed in
      89.2% of stage IIIA-IIIAB unexcised IT-mets. The overall limb recurrent disease
      in stage III was 39%. In patients with CR recurrent rate occurred in 44% with a
      mean limb recurrence-free interval (LRFI) of 23.8 months. Distant metastases was
      attained with a mean time of 29.2 months. After CR, the interval was 32.1 months.
      The 5-year survival rate was 45%; in patients with CR, was 48%. CONCLUSIONS: Our
      procedure is an important therapeutic option. The results suggest a marked local
      control of the recurrent disease. The LRFI is longer than for those treated with
      other treatment schedules.

PMID- 21721009
TI  - Extensive screening for primary tumor is redundant in melanoma of unknown
      primary.
AB  - For decades, patients in our institution with metastastic melanoma of unknown
      primary have been subjected to extensive examinations in search of the primary
      tumor. This retrospective study questions the results, and thus the feasibility
      of these examinations. Of 103 patients diagnosed with unknown primary tumor
      during the period 1986-2006, 39 (38%) presented primarily with a cutaneous or a
      subcutaneous metastasis, and 63 (61%) with a lymph node metastasis. One patient
      presented with a bone metastasis (1%). Eighty-seven patients (84%) were examined
      by an ophthalmologist. A choroidal melanoma was suspected as the primary tumor in
      one patient. Eighty-four patients (82%) were examined by an oto-rhino
      laryngologist, whereby no primary tumor was found. Ninety-five patients (92%)
      were examined by sigmoideoscopy/rectoscopy. No primary tumor was found. Of the 36
      women, 32 had a gynecological examination (89%), revealing no primary tumor. We
      conclude, that only one possible (but not verified) primary tumor was disclosed
      by various specialists examinations of 103 patients referred with the diagnosis
      metastatic melanoma with no primary tumor. Special screenings can thus be
      considered as redundant. Thus, for patients referred with metastastic melanoma of
      unknown primary, we recommend that a detailed history is obtained, and a standard
      physical examination performed, in addition to a histopathological review and
      CT/PET for staging.

PMID- 21721010
TI  - Prognostic impact of MMP-2 and MMP-9 expression in pathologic stage IA non-small
      cell lung cancer.
AB  - BACKGROUND: The purpose of the present study was to assess the value of matrix
      metalloproteinase (MMP)-2 and MMP-9 expression and other potential prognostic
      factors in predicting the clinical outcome of patients after definitive surgery
      for pathologic stage IA non-small cell lung cancer (NSCLC). METHODS: One hundred
      and forty-six consecutive and non-selected patients who underwent definitive
      surgery for stage IA NSCLC were included in this study. Formalin-fixed paraffin
      embedded specimens were stained for MMP-2 and MMP-9, which were statistically
      evaluated for their prognostic value and other clinicopathological parameters.
      RESULTS: Of the 146 patients studied, 102 (69.9%) cases were classified as having
      high expression for MMP-2. A total of 89 carcinomas (61.0%) had high expression
      for MMP-9. MMP-9 expression correlated with Eastern Cooperative Oncology Group
      (ECOG) performance status, pT stage, and differentiation (P = 0.005, <0.001, and
      <0.001, respectively). Vessel invasion, pT stage, and MMP-9 expression maintained
      their independent prognostic influence on overall survival (P = 0.037, <0.001,
      and <0.001, respectively). CONCLUSIONS: From results of our relatively large
      database, MMP-9 may be considered as a viable biomarker that can be used in
      conjunction with other prognostic factors such as vessel invasion and pT stage to
      predict the prognosis of patients with completely resected pathologic stage IA
      NSCLC.

PMID- 21721011
TI  - Prognostic significance of serum miRNA-21 expression in human non-small cell lung
      cancer.
AB  - BACKGROUND: Deregulation of microRNAs (miRNAs) plays important roles in tumor
      progression. The aim of this study was to investigate miR-21 expression in serum
      of non-small cell lung cancer (NSCLC) and its correlation with prognosis of NSCLC
      patients. METHODS: Dysregulated miRNAs in NSCLC serum were identified by
      microarray. MiR-21 expression in NSCLC and control serum was detected by TaqMan
      RT-PCR assay. The correlation of serum miR-21 with clinicopathological factors of
      NSCLC patients was analyzed. Furthermore, the prognostic significance of serum
      miR-21 was analyzed by using Kaplan-Meier curves with log-rank tests and a Cox
      proportional hazard model. RESULTS: The level of miR-21 expression was higher in
      NSCLC serum samples than in control serum samples (P < 0.01). High serum miR-21
      was significantly correlated with tumor-node metastases stage and lymph node
      metastasis of NSCLC patients (P = 0.016 and 0.026, respectively). The 3-year
      actuarial overall survival rates in NSCLC patients with high serum miR-21
      expression (39.8%) was significantly shorter than those with low serum miR-21
      expression (58.2%; P < 0.001). Furthermore, univariate and multivariate analyses
      for overall survival showed that serum miR-21 expression was an independent
      prognostic factor for NSCLC patients (P = 0.015, RR = 2.01, 95% CI: 1.78-3.26).
      CONCLUSION: Serum miR-21 expression might be useful as a prognostic marker for
      NSCLC patients.

PMID- 21721012
TI  - Robotic facelift thyroidectomy: II. Clinical feasibility and safety.
AB  - OBJECTIVES: A number of remote access thyroidectomy techniques have been
      described in the last several years. These approaches are technically
      challenging, can be performed on only a limited patient population, and have been
      associated with significant complications. We describe a novel robotic facelift
      approach for thyroidectomy and report our initial clinical experience. DESIGN:
      Planned analysis of a prospectively maintained database with institutional review
      board approval. METHODS: Robotic facelift thyroidectomy (RFT) was performed on
      all patients. Demographic and surgical data were obtained and analyzed. Data
      collected included patient age, gender, body mass index (BMI), pathology,
      complications, and duration of surgery. RESULTS: A total of 18 RFT procedures
      were undertaken in 14 patients. There were 13 females and 1 male, with a mean age
      of 33.7 +/- 18.1 years (range: 12-70). The mean BMI was 26.9 +/- 4.5. The
      procedures included 13 lobectomies, one bilateral thyroidectomy, and 3 completion
      thyroidectomies. All but the first procedure was performed on an outpatient basis
      without use of a drain. There were no conversions to open surgery, no permanent
      nerve injuries, and no cases of hypoparathyroidism. Operative times ranged from
      97 to 193 minutes. CONCLUSIONS: RFT is a feasible remote access thyroidectomy
      approach. It appears from our initial experience that it may be performed in a
      safe and reproducible manner without a drain and on an outpatient basis.
      Additional clinical experience is warranted to further validate this technique.

PMID- 21721013
TI  - Malignant phosphaturic mesenchymal tumor of the larynx.
AB  - Phosphaturic mesenchymal tumors are rare neoplasms predominantly originating in
      the trunk and extremities. Malignant variants are exceedingly rare, and can
      present significant diagnostic challenges to the pathologist and otolaryngologist
      alike. This report describes the first case of malignant phosphaturic mesenchymal
      tumor involving the larynx, and emphasizes the importance of vigilance in both
      histopathologic and clinical actions so that appropriate treatment can be
      provided in a timely manner. The clinical presentation, radiologic and histologic
      features, and management are discussed.

PMID- 21721014
TI  - Neurocognitive development and externalizing problems: the role of inhibitory
      control deficits from 4 to 6 years.
AB  - Executive processes have been posited as important regulators of externalizing
      problems (EP), but there has been little research on the relation between
      executive dysfunction and EP in early childhood. During the preschool period,
      maturation of the prefrontostriatal circuitry parallels increases in inhibitory
      control (IC). Poor IC development could result in elevated levels of aggressive,
      disruptive, and impulsive behavior. In this investigation, the development of the
      relation between IC and EP was examined in preschool and early elementary school
      children using the Day/Night and Tapping tasks. Children with more EP made more
      incorrect responses on both IC tasks, consistently across age and sex. The
      associations between EP and response latencies differed across children, however,
      with longer latencies on the Tapping task being most characteristic for boys with
      high levels of EP. This association was not apparent for girls. Two prominent
      aspects of early EP, aggressive and inattentive behavior, showed only weak unique
      associations with IC performance. These findings imply that diminished IC
      accompanies elevated EP as early as the preschool years, and that this decrement
      persists into the elementary school-age years for both girls and boys, and that
      accuracy and response latency may confer different information about the
      development of IC.

PMID- 21721015
TI  - Isolated hypertrophy of the tibialis anterior muscle in the stiff leg syndrome.

PMID- 21721016
TI  - Beneficial effect of albuterol in congenital myasthenic syndrome with epsilon
      subunit mutations.
AB  - Mutations in the epsilon subunit of the acetylcholine receptor (AChR) are a
      common cause of congenital myasthenic syndrome (CMS). Patients are usually
      treated with acetylcholinesterase inhibitors and 3,4-diaminopyridine with modest
      clinical benefit. We report 2 patients with CMS due to mutations in the AChR
      epsilon subunit. The first patient carries two heterozygous frameshift mutations,
      epsilon127ins5 and epsilon1293insG. The second patient is homozygous for the
      epsilonC142Y mutation that curtails AChR expression to 22% of wild-type in HEK
      cells. Treatment with pyridostigmine and 3,4-diaminopyridine had a limited
      beneficial effect in the first patient, and the second patient became wheelchair
      bound during therapy. The additional use of albuterol produced dramatic
      improvement in strength and in activities of daily living in both patients. The
      efficacy and safety of albuterol in patients who harbor identified low-expressor
      or null mutations in the epsilon or other subunits of AChR merits a well-designed
      clinical trial.

PMID- 21721017
TI  - Vanadium pentoxide induces activation and death of endothelial cells.
AB  - Vanadium is a transition metal released into the atmosphere, as air-suspended
      particles, as a result of the combustion of fossil fuels and some metallurgic
      industry activities. Air-suspended particle pollution causes inflammation-related
      processes such as thrombosis and other cardiovascular events. Our aim was to
      evaluate the effect of vanadium pentoxide (V2O5) on endothelial cells since they
      are key participants in the pathogenesis of several cardiovascular and
      inflammatory diseases. Cell adhesion, the expression of adhesion molecules and
      oxidative stress, as well as proliferation, morphology and cell death of human
      umbilical vein endothelial cells (HUVECs) exposed to V2O5, were evaluated.
      Vanadium pentoxide at a 3.12 ug cm(-2) concentration induced an enhanced adhesion
      of the U937 macrophage cell line to HUVECs, owing to an increased expression of
      late adhesion molecules. HUVECs exposed to V2O5 showed an increase in ROS and
      nitric oxide production, and a diminished proliferation. These changes in
      vanadium-treated HUVECs were accompanied by severe morphological changes and
      apoptotic cell death. Vanadium pentoxide induced serious endothelial cell damage,
      probably related to the increased cardiovascular morbidity and mortality observed
      in individuals living in highly air-polluted areas.

PMID- 21721018
TI  - An intravenous exposure mouse model for prediction of potential drug
      sensitization using reporter antigens popliteal lymph node assay.
AB  - Immune-mediated drug hypersensitivity is a particularly concerning health-safety
      issue among clinicians given its unpredictability and potentially life
      threatening effects, especially with exposure to intravenous drugs. Therefore,
      the development of intravenous drug-exposure models for drug-hazard assessments
      has garnered increasing interest in recent years. In this study, we used reporter
      antigens popliteal lymph node assay to investigate the potential value of
      intravenous exposure to a selected variety of allergenic compounds, including
      ovalbumin (OVA), concanavalin A (ConA) and diclofenac. The trinitrophenyl (TNP)
      specific antibody-forming cells were used to assess the systemic immune responses
      to a bystander antigen. Mice were subsequently sensitized by TNP-OVA, and then
      intravenous exposure to one of the selective compounds. As expected, all positive
      compounds induced significant popliteal lymph node (PLN) proliferation compared
      with the control. OVA significantly increased Cluster of Differentiation 4
      receptors (CD4)+ interleukin-4 (IL-4)+ T-helper 2 (Th2) cells and, consequently,
      increased the ratios of IL-4/interferon-gamma (IFN-gamma) antibody-forming cells
      (AFCs) in PLNs, while bringing about a dose-dependent increase in immunoglobulin
      G1 (IgG1) AFCs; these findings indicate that a Th2 hypersensitivity response was
      induced. A Th2 response was also observed in diclofenac sodium-treated groups,
      and for ConA, a more mixed Th1/Th2 immune response appeared to be induced. In
      addition, there was no marked reaction with the negative compound. Together, it
      seems likely that the intravenous exposure model may be useful for drug-induced
      systemic hypersensitivity assessments.

PMID- 21721019
TI  - Caffeine induction of sulfotransferases in rat liver and intestine.
AB  - Sulfotransferases (SULTs) are important phase II drug-metabolizing enzymes.
      Regulation of SULTs by hormones and other endogenous molecules is relatively well
      understood, while xenobiotic induction of SULTs is not well studied. Caffeine is
      one of the most widely consumed psychoactive substances. However, SULT regulation
      by caffeine has not been reported. In this report, male and female rats were
      treated with different oral doses of caffeine (2, 10, 50 mg kg-1 per day) for 7
      days. Western blot and real-time RT-PCR were used to investigate the changes in
      SULT protein and mRNA expression following the caffeine treatment. Caffeine
      induced both rat aryl sulfotransferase (rSULT1A1, AST-IV) and rat hydroxysteroid
      sulfotransferase (rSULT2A1, STa) in the liver and intestine of female rats in a
      dose-dependent manner. Caffeine induction of rSULT1A1 and rSULT2A1 in the female
      rat intestine was much stronger than that in the liver. Although caffeine induced
      rSULT1A1 significantly in the male rat liver, it did not significantly induce
      rSULT2A1. In male rat intestine, caffeine significantly induced rSULT2A1. The
      different SULTs induction patterns in male and female rats suggest that the
      regulation of rat SULTs by caffeine may be affected by different hormone
      secretion patterns and levels. Our results suggest that consumption of caffeine
      can induce drug metabolizing SULTs in drug detoxification tissues.

PMID- 21721020
TI  - Cloning, expression and functional characterization of carp, Cyprinus carpio,
      estrogen receptors and their differential activations by estrogens.
AB  - Sex-steroid hormones are essential for normal reproductive activity in both
      sexes. Estrogens are necessary for ovarian differentiation during a critical
      developmental stage in vertebrates and promote the growth and differentiation of
      the female reproductive system. Importantly, environmental estrogens can
      influence the reproductive system and have been shown to disrupt gametogenesis in
      males. To understand the molecular mechanisms of estrogen actions and to evaluate
      estrogen receptor ligand interactions in the carp, Cyprinus carpio, a species
      used widely for both field- and laboratory-based studies, we cloned all three
      carp estrogen receptors (ER; ERalpha, ERbeta1 and ERbeta2) and applied an
      estrogen-responsive (ERE)-luciferase reporter assay system to characterize the
      interactions of these receptors with steroidal and synthetic estrogens. DNA
      fragments encoding all three ERs in carp, ERalpha, ERbeta1 and ERbeta2, were
      obtained from the ovary using degenerate primer sets and PCR techniques, and full
      length carp ER (cER) cDNAs were then obtained using RACE (rapid amplification of
      the cDNA end) techniques. Amino acid sequences of cERs showed overall homology of
      46% (alpha vs beta1), 49% (alpha vs beta2) and 53% (beta1 vs beta2). In the
      transient transfection ERE-luciferase reporter assay system (using mammalian
      cells) the cER proteins displayed estrogen-dependent activation of transcription
      and cERbeta2 showed a higher sensitivity to the natural steroid oestrogen, 17beta
      estradiol, than cERalpha. The assay system developed is a powerful assay for
      toxicology and provides a tool for future studies examining the receptor
      environmental chemical interactions and estrogen-disrupting mechanisms in carp.
      The data presented also expand our knowledge of estrogen receptor evolution.

PMID- 21721021
TI  - Plant-originated glycoprotein (24 kDa) has an inhibitory effect on proliferation
      of BNL CL.2 cells in response to di(2-ethylhexyl)phthalate.
AB  - Di(2-ethylhexyl)phthalate (DEHP) is one of the many environmental chemicals that
      are widely used in polyvinyl chloride products, vinyl flooring, food packaging
      and infant toys. They cause cell proliferation or dysfunction of human liver. The
      purpose of this study is to investigate the inhibitory effect of a glycoprotein
      (24 kDa) isolated from Zanthoxylum piperitum DC (ZPDC) on proliferation of liver
      cell in the DEHP-induced BNL CL. 2 cells. [3H]-thymidine incorporation,
      intracellular reactive oxygen species (ROS), intracellular Ca2+ mobilization and
      activity of protein kinase C (PKC) were measured using radioactivity and
      fluorescence method respectively. The expression of mitogen-activated protein
      kinases [extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase
      (JNK)], activator protein (AP)-1 (c-Jun and c-Fos), proliferating cell nuclear
      antigen (PCNA) and cell cycle-related factors (cyclin D1/cyclin-dependent kinase
      [CDK] 4) were evaluated using Western blotting or electrophoretic mobility shift
      assay. The results in this study showed that the levels of [3H]-thymidine
      incorporation, intracellular ROS, intracellular Ca2+ mobilization and activity of
      PKCalpha were inhibited by ZPDC glycoprotein (100 ug/ml) in the DEHP-induced BNL
      CL. 2 cells. Also, activities of ERK, JNK and AP-1 were reduced by ZPDC
      glycoprotein (100 ug/ml). With regard to cell proliferation, activities of PCNA
      and cyclin D1/CDK4 were significantly suppressed at treatment with ZPDC
      glycoprotein (100 ug/ml) in the presence of DEHP. Taken together, these findings
      suggest that ZPDC glycoprotein significantly normalized activities of PCNA and
      cyclin D1/CDK4, which relate to cell proliferation factors. Thus, ZPDC
      glycoprotein appears to be one of the compounds derived from natural products
      that are able to inhibit cell proliferation in the phthalate-induced BNL CL. 2
      cells.

PMID- 21721022
TI  - A simple LC-MS/MS method to determine plasma and cerebrospinal fluid levels of
      albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in
      patients with neurocysticercosis.
AB  - The development and validation of an LC-MS/MS method for the simultaneous
      determination of albendazole metabolites (albendazole sulfoxide and albendazole
      sulfone) in human plasma are described. Samples of 200 MUL were extracted with
      ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic
      separation was performed using a C(18) column with methanol-formic acid 20 mmol/L
      (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL
      for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both
      analytes the method was precise (RSD < 12%) and accurate (RE <7%) with high
      recovery (>90%). The method was successfully applied to determine the plasma and
      cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in
      patients with subarachnoidal neurocysticercosis who received albendazole at 30
      mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and
      reliable protocol for determining albendazole sulfoxide and albendazole sulfone
      concentrations in plasma and cerebrospinal fluid samples and is applicable to
      therapeutic monitoring.

PMID- 21721023
TI  - Development and validation of a method for the determination of buprenorphine and
      norbuprenorphine in breast milk by gas chromatography-mass spectrometry.
AB  - Buprenorphine (BUP) is used for the maintenance of opioid-addicted pregnant
      women. Because BUP and its main metabolite nor-BUP are excreted into breast milk,
      a sensitive and specific GC/MS method has been developed, optimized and validated
      for their determination in breast milk. BUP-d4 was used as internal standard. The
      sample preparation includes combination of protein precipitation with solid-phase
      extraction and derivatization (acetylation). The absolute recovery for both
      analytes was found to be higher than 87.3%. The limits of detection and
      quantification were 0.07 and 0.20 ug/L, respectively. The calibration curves were
      linear within the dynamic range 0.20-20.0 ug/L, with a correlation coefficient
      higher than 0.996. Intra- and inter-day accuracies were ranged from -7.06 to 4.50
      and from -5.88 to 7.00%, respectively, while intra- and inter-day precision were
      less than 5.7 and 6.1%. The analytes were found to be stable in breast milk at 4 
      degrees C for one week, at -20  degrees C for one month, and after three freeze
      thaw cycles. The method can be used for the determination of BUP and nor-BUP in
      breast milk of BUP-maintained mothers, in order to calculate the amount of drug
      that could pass to the newborn via breast milk and to avoid toxic consequences of
      breastfeeding.

PMID- 21721024
TI  - Virological breakthrough and resistance in patients with chronic hepatitis B
      receiving nucleos(t)ide analogues in clinical practice.

PMID- 21721025
TI  - Fighting against viral hepatitis: lessons from Taiwan.
AB  - Viral hepatitis and its sequelae are important health problems worldwide,
      including Taiwan. For the last 40 years, Taiwan's scientists and health care
      providers have worked hard to control these sequelae, and the results have been
      excellent. The author, Ding-Shinn Chen, had a key role in planning and
      establishing the control program in Taiwan, and participated in the endeavors
      from the very beginning. In this perspective, he describes how he became
      interested in research as a medical student, his encounters with hepatitis B and
      C, how he and his colleagues started early detection of hepatocellular carcinoma
      (HCC), how he helped Taiwan's government create and implement the Viral Hepatitis
      Control Program, and how the effectiveness of the program in the decrease of
      hepatitis B carriage and HCC was monitored. He also discusses how he pioneered
      the use of interferon-alpha plus ribavirin to treat chronic hepatitis C.
      Hepatitis B viral load as a risk factor for HCC and cirrhosis in hepatitis B
      surface antigen carriers is reviewed briefly, as is the prevention of sequelae by
      antiviral therapies. Finally, Dr. Chen discusses unresolved issues that must be
      addressed and predicts the changes of the patterns of liver disease in Taiwan
      beyond the mid-21st century, which is in part affected by the fight against viral
      hepatitis that was initiated in the early 1980s. CONCLUSION: Dr. Chen's
      perspective illustrates Taiwan's fight against viral hepatitis over the last 40
      years. This experience can be shared by other countries in which the disease is
      equally prevalent.

PMID- 21721026
TI  - Endogenous histones function as alarmins in sterile inflammatory liver injury
      through Toll-like receptor 9 in mice.
AB  - Sterile inflammatory insults are known to activate innate immunity and propagate
      organ damage through the recognition of extracellular damage-associated molecular
      pattern (DAMP) molecules. Although DAMPs such as endogenous DNA and nuclear high
      mobility group box 1 have been shown to be critical in sterile inflammation, the
      role of nuclear histone proteins has not yet been investigated. We report that
      endogenous histones function as DAMPs after ischemic injury through the pattern
      recognition receptor Toll-like receptor (TLR) 9 to initiate inflammation. Using
      an in vivo model of hepatic ischemia/reperfusion (I/R) injury, we show that
      levels of circulating histones are significantly higher after I/R, and that
      histone neutralization significantly protects against injury. Injection of
      exogenous histones exacerbates I/R injury through cytotoxic effects mediated by
      TLR9 and MyD88. In addition, histone administration increases TLR9 activation,
      whereas neither TLR9 nor MyD88 mutant mice respond to exogenous histones.
      Furthermore, we demonstrate in vitro that extracellular histones enhance DNA
      mediated TLR9 activation in immune cells through a direct interaction.
      CONCLUSION: These novel findings reveal that histones represent a new class of
      DAMP molecules and serve as a crucial link between initial damage and activation
      of innate immunity during sterile inflammation.

PMID- 21721027
TI  - Novel poly (ADP-ribose) polymerase 1 binding motif in hepatitis B virus core
      promoter impairs DNA damage repair.
AB  - It is well-established that hepatitis B virus (HBV) infection is associated with
      the development of hepatocellular carcinoma (HCC), but patients with high viral
      DNA load have significantly higher risk. As host factors are required for
      efficient viral replication and may, therefore, contribute to high viral DNA
      load, we screened for host factors that can transcriptionally activate the HBV
      core promoter (HBVCP). We report here that poly (ADP-ribose) polymerase 1
      (PARP1), which is known for its DNA repair activity, binds prominently to an
      octamer motif in the HBVCP and increases transcriptional efficiency. By utilizing
      a series of single base substitutions at each nucleotide position of the octamer,
      the PARP1 binding motif can be defined as "RNNWCAAA." Intriguingly, introduction
      of a vector construct bearing tandem repeats of the octamer motif was able to
      impair the DNA repair function of PARP1. This finding suggests that HBV viral DNA
      contains specific sequence motifs that may play a role in disrupting the DNA
      repair pathways of infected hepatocytes. CONCLUSION: This study has identified a
      novel octamer motif in the HBVCP that binds PARP1, and this interaction increases
      the replication efficiency of HBV. The presence of this octamer motif in
      hepatocytes was shown to inhibit the DNA repair capacity of PARP1, potentially
      contributing to the development of HCC.

PMID- 21721028
TI  - Genetic variation in the interleukin-28B gene is not associated with fibrosis
      progression in patients with chronic hepatitis C and known date of infection.
AB  - Polymorphisms in the interleukin-28B (IL28B) region are associated with
      spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV)
      infection. Nevertheless, it is unknown whether genetic variation at the IL28B
      locus influences the natural history of chronic HCV infection. Thus, we asked
      whether an association between IL28B polymorphisms and liver fibrosis progression
      existed. We studied 247 consecutive patients with chronic HCV, an accurate
      estimate of the date of infection, and a liver biopsy performed before any
      treatment. No patient had a history of alcohol abuse or coinfection with other
      viruses. We assessed the role of rs8099917 and rs12979860 polymorphisms and the
      effect of host and environmental factors on fibrosis progression. Blood
      transfusion (75%) was the main modality of infection. Median age at infection was
      21 years, and median interval between infection and liver biopsy was 25 years.
      One hundred twenty-nine patients (52%) were infected by HCV-1, 74 (30%) by HCV-2,
      34 (14%) by HCV-3, and 10 (4%) by HCV-4. Bridging fibrosis/cirrhosis (Ishak >= 4)
      was detected in 24% of patients. Age at infection had a marked effect on fibrosis
      progression by both a linear model and Cox proportional-hazard regression (P < 2E
      16). A 12.1% increase in the hazard of advanced fibrosis was estimated for each
      additional year at infection, suggesting that this was the major explanatory
      variable in this cohort. Male gender (P < 0.05), HCV genotype 3 (P < 0.001) and
      steatosis (P < 0.05) were also associated with faster fibrosis progression.
      Conversely, the two IL28B polymorphisms had no impact on fibrosis progression.
      CONCLUSION: In HCV patients with a known date of infection, IL28B genotype was
      not associated with fibrosis progression rate or with the risk of developing
      advanced liver fibrosis.

PMID- 21721029
TI  - Intercellular nanovesicle-mediated microRNA transfer: a mechanism of
      environmental modulation of hepatocellular cancer cell growth.
AB  - Hepatocellular carcinoma (HCC) is characterized by a propensity for
      multifocality, growth by local spread, and dysregulation of multiple signaling
      pathways. These features may be determined by the tumoral microenvironment. The
      potential of tumor cells to modulate HCC growth and behavior by secreted proteins
      has been extensively studied. In contrast, the potential for genetic modulation
      is poorly understood. We investigated the role and involvement of tumor-derived
      nanovesicles capable of altering gene expression and characterized their ability
      to modulate cell signaling and biological effects in other cells. We show that
      HCC cells can produce nanovesicles and exosomes that differ in both RNA and
      protein content from their cells of origin. These can be taken up and
      internalized by other cells and can transmit a functional transgene. The microRNA
      (miRNA) content of these exosomes was examined, and a subset highly enriched
      within exosomes was identified. A combinatorial approach to identify potential
      targets identified transforming growth factor beta activated kinase-1 (TAK1) as
      the most likely candidate pathway that could be modulated by these miRNAs. Loss
      of TAK1 has been implicated in hepatocarcinogenesis and is a biologically
      plausible target for intercellular modulation. We show that HCC cell-derived
      exosomes can modulate TAK1 expression and associated signaling and enhance
      transformed cell growth in recipient cells. CONCLUSION: Exosome-mediated miRNA
      transfer is an important mechanism of intercellular communication in HCC cells.
      These observations identify a unique intercellular mechanism that could
      potentially contribute to local spread, intrahepatic metastases, or multifocal
      growth in HCC.

PMID- 21721030
TI  - Reversal of hepatitis B virus-induced immune tolerance by an immunostimulatory 3p
      HBx-siRNAs in a retinoic acid inducible gene I-dependent manner.
AB  - It is extensively accepted that hepatitis B virus (HBV) escapes from innate
      immunity by inhibiting type I interferon (IFN) production, but efficient
      intervention to reverse the immune tolerance is still not achieved. Here, we
      report that 5'-end triphosphate hepatitis B virus X gene (HBx)-RNAs (3p-HBx-short
      interfering [si]RNAs) exerted significantly stronger inhibitory effects on HBV
      replication than regular HBx-siRNAs in stably HBV-expressing hepatoplastoma
      HepG2.2.15 cells through extremely higher expression of type I IFNs, IFN-induced
      genes and proinflammatory cytokines, and retinoic acid inducible gene I (RIG-I)
      activation. Also, 3p-HBx-siRNA were more efficient to stimulate type I IFN
      response than HBx sequence-unrelated 3p-scramble-siRNA in HepG2.2.15 cells,
      indicating that a stronger immune-stimulating effect may partly result from the
      reversal of immune tolerance through decreasing HBV load. In RIG-I-overexpressed
      HepG2.2.15 cells, 3p-HBx-siRNAs exerted stronger inhibitory effects on HBV
      replication with greater production of type I IFNs; on the contrary, in RIG-I
      silenced HepG2.2.15 cells or after blockade of IFN receptor by monoclonal
      antibody, inhibitory effect of 3p-HBx-siRNAs on HBV replication was largely
      attenuated, indicating that immunostimulatory function of 3p-HBx-siRNAs was RIG-I
      and type I IFN dependent. Moreover, in HBV-carrier mice, 3p-HBx-siRNA more
      strongly inhibited HBV replication and promoted IFN production than HBx-siRNA in
      primary HBV(+) hepatocytes and, therefore, significantly decreased serum
      hepatitis B surface antigen and increased serum IFN-beta. CONCLUSION: 3p-HBx
      siRNAs may not only directly inhibit HBV replication, but also stimulate innate
      immunity against HBV, which are both beneficial for the inversion of HBV-induced
      immune tolerance.

PMID- 21721031
TI  - Spontaneous repopulation of beta-catenin null livers with beta-catenin-positive
      hepatocytes after chronic murine liver injury.
AB  - Prolonged exposure of mice to diet containing 0.1% 3,5-diethoxycarbonyl-1,4
      dihydrocollidine (DDC) results in hepatobiliary injury, atypical ductular
      proliferation, oval cell appearance, and limited fibrosis. Previously, we
      reported that short-term ingestion of DDC diet by hepatocyte-specific beta
      catenin conditional knockout (KO) mice led to fewer A6-positive oval cells than
      wildtype (WT) littermates. To examine the role of beta-catenin in chronic hepatic
      injury and repair, we exposed WT and KO mice to DDC for 80 and 150 days.
      Paradoxically, long-term DDC exposure led to significantly more A6-positive
      cells, indicating greater atypical ductular proliferation in KO, which coincided
      with increased fibrosis and cholestasis. Surprisingly, at 80 and 150 days in KO
      we observed a significant amelioration of hepatocyte injury. This coincided with
      extensive repopulation of beta-catenin null livers with beta-catenin-positive
      hepatocytes at 150 days, which was preceded by appearance of beta-catenin
      positive hepatocyte clusters at 80 days and a few beta-catenin-positive
      hepatocytes at earlier times. Intriguingly, occasional beta-catenin-positive
      hepatocytes that were negative for progenitor markers were also observed at
      baseline in the KO livers, suggesting spontaneous escape from cre-mediated
      recombination. These cells with hepatocyte morphology expressed mature hepatocyte
      markers but lacked markers of hepatic progenitors. The gradual repopulation of KO
      livers with beta-catenin-positive hepatocytes occurred only following DDC injury
      and coincided with a progressive loss of hepatic cre-recombinase expression. A
      few beta-catenin-positive cholangiocytes were observed albeit only after long
      term DDC exposure and trailed the appearance of beta-catenin-positive
      hepatocytes. CONCLUSION: In a chronic liver injury model, beta-catenin-positive
      hepatocytes exhibit growth and survival advantages and repopulate KO livers,
      eventually limiting hepatic injury and dysfunction despite increased fibrosis and
      intrahepatic cholestasis.

PMID- 21721032
TI  - Cross-presentation of antigen by diverse subsets of murine liver cells.
AB  - Antigen cross-presentation is a principal function of specialized antigen
      presenting cells of bone marrow origin such as dendritic cells. Although these
      cells are sometimes known as "professional" antigen-presenting cells, nonbone
      marrow-derived cells may also act as antigen-presenting cells. Here, using four
      way liver cell isolation and parallel comparison of candidate antigen-presenting
      cells, we show that, depending on the abundance of antigen-donor cells, different
      subsets of liver cells could cross-present a hepatocyte-associated antigen. This
      function was observed in both liver sinusoidal endothelial cells and Kupffer
      cells even at very low antigen concentration, as well as when using soluble
      protein. Antigen cross-presentation by liver cells induced efficient CD8+ T-cell
      proliferation in a similar manner to classical dendritic cells from spleen.
      However, proliferated cells expressed a lower level of T-cell activation markers
      and intracellular interferon-gamma levels. In contrast to classical spleen
      dendritic cells, cross-presentation by liver antigen-presenting cells was
      predominantly dependent on intercellular adhesion molecule-1. CONCLUSION: Hepatic
      sinusoids are an environment rich in antigen cross-presenting activity. However,
      the liver's resident antigen-presenting cells cause partial T-cell activation.
      These results clarify how the liver can act as a primary site of CD8+ T-cell
      activation, and why immunity against hepatocyte pathogens is sometimes
      ineffective.

PMID- 21721033
TI  - Induced pluripotent stem cell models from X-linked adrenoleukodystrophy patients.
AB  - OBJECTIVE: Because of a lack of an appropriate animal model system and the
      inaccessibility of human oligodendrocytes in vivo, X-linked adrenoleukodystrophy
      (X-ALD)-induced pluripotent stem cells (iPSCs) would provide a unique cellular
      model for studying etiopathophysiology and development of therapeutics for X-ALD.
      METHODS: We generated and characterized iPSCs of the 2 major types of X-ALD,
      childhood cerebral ALD (CCALD) and adrenomyeloneuropathy (AMN), and
      differentiated them into oligodendrocytes and neurons. We evaluated disease
      relevant phenotypes by pharmacological and genetic approaches. RESULTS: We
      established iPSCs from the patients with CCALD and AMN. Both CCALD and AMN iPSCs
      normally differentiated into oligodendrocytes, the cell type primarily affected
      in the X-ALD brain, indicating no developmental defect due to the ABCD1
      mutations. Although low in X-ALD iPSCs, very long chain fatty acid (VLCFA) level
      was significantly increased after oligodendrocyte differentiation. VLCFA
      accumulation was much higher in CCALD oligodendrocytes than AMN oligodendrocytes
      but was not significantly different between CCALD and AMN neurons, indicating
      that the severe clinical manifestations in CCALD might be associated with
      abnormal VLCFA accumulation in oligodendrocytes. Furthermore, the abnormal
      accumulation of VLCFA in the X-ALD oligodendrocytes can be reduced by the
      upregulated ABCD2 gene expression after treatment with lovastatin or 4
      phenylbutyrate. INTERPRETATION: X-ALD iPSC model recapitulates the key events of
      disease development (ie, VLCFA accumulation in oligodendrocytes), provides new
      clues for better understanding of the disease, and allows for early and accurate
      diagnosis of the disease subtypes. X-ALD oligodendrocytes can be a useful cell
      model system to develop new therapeutics for treating X-ALD.

PMID- 21721034
TI  - A linear solvation energy relationship model of organic chemical partitioning to
      dissolved organic carbon.
AB  - Predicting the association of contaminants with both particulate and dissolved
      organic matter is critical in determining the fate and bioavailability of
      chemicals in environmental risk assessment. To date, the association of a
      contaminant to particulate organic matter is considered in many multimedia
      transport models, but the effect of dissolved organic matter is typically ignored
      due to a lack of either reliable models or experimental data. The partition
      coefficient to dissolved organic carbon (K(DOC)) may be used to estimate the
      fraction of a contaminant that is associated with dissolved organic matter.
      Models relating K(DOC) to the octanol-water partition coefficient (K(OW)) have
      not been successful for many types of dissolved organic carbon in the
      environment. Instead, linear solvation energy relationships are proposed to model
      the association of chemicals with dissolved organic matter. However, more
      chemically diverse K(DOC) data are needed to produce a more robust model. For
      humic acid dissolved organic carbon, the linear solvation energy relationship
      predicts log K(DOC) with a root mean square error of 0.43.

PMID- 21721035
TI  - A linear solvation energy relationship model of organic chemical partitioning to
      particulate organic carbon in soils and sediments.
AB  - Predicting the association of contaminants with particulate organic matter in the
      environment is critical in determining the fate and bioavailability of chemicals.
      A ubiquitous measure of contaminant association with soil and sediment
      particulate organic matter is the organic carbon partition coefficient K(OC) .
      Chemical class-specific models relating the K(OC) to the octanol-water partition
      coefficient K(OW) have been used to predict the partitioning to organic carbon in
      the water column and sediment for nonpolar hydrophobic pollutants and some polar
      pollutants. A single linear solvation energy relationship (LSER) is proposed as a
      simpler and chemically based alternative for predicting K(OC) for a more diverse
      set of compounds. A chemically diverse set of K(OC) data is used to obtain a more
      robust and more universally representative model of organic carbon partitioning
      than previously available LSER models. The resulting model has a root mean square
      error (RMSE) of prediction for log K(OC) of RMSE = 0.48 for the fitted data set
      and RMSE = 0.55 for an independent data set. An analysis of LSER coefficients
      highlights the relative importance of hydrogen bonding interactions.

PMID- 21721036
TI  - Effect of zinc on diversity of riverine benthic macroinvertebrates: estimation of
      safe concentrations from field data.
AB  - We conducted field surveys at 25 sites in three Japanese catchments to provide
      conservative estimates of the safe concentration of zinc (Zn) for the protection
      of riverine macroinvertebrate diversity. The relationships between the Zn
      concentration and six macroinvertebrate metrics for taxon richness were
      determined by using regression analysis; this included a piecewise regression
      model, where two lines are joined at an unknown point. For each metric the
      piecewise regression model with a zero slope below a threshold concentration was
      selected as the best model to explain the influence of Zn. Under the assumption
      that macroinvertebrate diversity reductions of <10% are acceptable, the safe
      concentrations of Zn were estimated to be 84, 115, 84, 80, 85, and 70 ug/L for
      total taxon richness, Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness,
      mayfly richness, caddisfly richness, chironomid richness, and estimated total
      taxon richness at the riffle scale, respectively. These concentrations are more
      than twice the water quality standard for Zn in Japan (30 ug/L), suggesting that
      the standard is likely overprotective for macroinvertebrate diversity. Field
      studies are useful for evaluating the level of protectiveness of safe
      concentrations (water quality standards) based on individual-level effects from
      laboratory toxicity tests, and this evaluation process will have a crucial role
      in implementing more purpose-driven ecological risk managements that aim to
      protect natural populations and communities.

PMID- 21721037
TI  - Glioma cell density in a rat gene therapy model gauged by water relaxation rate
      along a fictitious magnetic field.
AB  - Longitudinal and transverse rotating-frame relaxation time constants, T(1) (rho)
      and T(2) (rho) , have previously been successfully applied to detect gene therapy
      responses and acute stroke in animal models. Those experiments were performed
      with continuous-wave irradiation or with frequency-modulated pulses operating in
      an adiabatic regime. The technique called Relaxation Along a Fictitious Field
      (RAFF) is a recent extension of frequency-modulated rotating-frame relaxation
      methods. In RAFF, spin locking takes place along a fictitious magnetic field, and
      the decay rate is a function of both T(1rho) and T(2rho) processes. In this work,
      the time constant characterizing water relaxation with RAFF (T(RAFF) ) was
      evaluated for its utility as a marker of response to gene therapy in a rat glioma
      model. To investigate the sensitivity to early treatment response, we measured
      several rotating-frame and free-precession relaxation time constants and the
      water apparent diffusion coefficients, and these were compared with histological
      cell counts in 8 days of treated and control groups of animals. T(RAFF) was the
      only parameter exhibiting significant association with cell density in three
      different tumor regions (border, intermediate, and core tissues). These results
      indicate that T(RAFF) may provide a marker to identify tumors responding to
      treatment.

PMID- 21721038
TI  - Rapid quantification of myocardial lipid content in humans using single breath
      hold 1H MRS at 3 Tesla.
AB  - A rapid, proton magnetic resonance spectroscopy method to evaluate human
      myocardial lipid levels in a single breath-hold at 3 T using a commercial whole
      body system is presented. During a 10 s breath-hold, water unsuppressed and
      suppressed spectra were acquired by two phased array coils using a short-echo
      time spectroscopic stimulated echo (STEAM) sequence electrocardiogram-triggered
      to mid-diastole. Lipid-to-water ratios were obtained in the septum of 15 healthy
      volunteers, (0.46 +/- 0.19)%. These results agreed well with ratios obtained from
      averaged spectra acquired in seven multiple breath-holds, (0.45 +/- 0.20)%,
      providing increased signal-to-noise ratio but requiring longer acquisition times.
      Excellent correlation was found between the two methods (r=0.94, P<0.05).
      Reproducibility of (1)H MRS for measuring myocardial lipid levels in a short
      breath-hold was acceptable in five repeated measurements within the same subject
      (coefficient of variation=19%). Thus, single breath-hold proton spectroscopy
      allows reliable and quick quantification of myocardial lipids at 3 T.

PMID- 21721039
TI  - Ultrashort echo time imaging using pointwise encoding time reduction with radial
      acquisition (PETRA).
AB  - Sequences with ultrashort echo times enable new applications of MRI, including
      bone, tendon, ligament, and dental imaging. In this article, a sequence is
      presented that achieves the shortest possible encoding time for each k-space
      point, limited by pulse length, hardware switching times, and gradient
      performance of the scanner. In pointwise encoding time reduction with radial
      acquisition (PETRA), outer k-space is filled with radial half-projections,
      whereas the centre is measured single pointwise on a Cartesian trajectory. This
      hybrid sequence combines the features of single point imaging with radial
      projection imaging. No hardware changes are required. Using this method, 3D
      images with an isotropic resolution of 1 mm can be obtained in less than 3
      minutes. The differences between PETRA and the ultrashort echo time (UTE)
      sequence are evaluated by simulation and phantom measurements. Advantages of
      pointwise encoding time reduction with radial acquisition are shown for tissue
      with a T(2) below 1 ms. The signal to noise ratio and Contrast-to-noise ratio
      (CNR) performance, as well as possible limitations of the approach, are
      investigated. In-vivo head, knee, ankle, and wrist examples are presented to
      prove the feasibility of the sequence. In summary, fast imaging with ultrashort
      echo time is enabled by PETRA and may help to establish new routine clinical
      applications of ultrashort echo time sequences.

PMID- 21721040
TI  - Selective excitation of two-dimensional arbitrarily shaped voxels with parallel
      excitation in spectroscopy.
AB  - Parallel excitation is being studied intensively for applications in MR imaging
      and in particular for selecting arbitrary shapes as regions of interest. In this
      work, parallel excitation was applied to arbitrarily shaped voxel selection in
      spectroscopy and investigated for different excitation k-space trajectories
      (radial, rectilinear, and spiral) and acceleration factors. Each trajectory was
      segmented into multiple excitations to increase the overall bandwidth during
      target selection. Acceleration by parallel excitation was used to decrease the
      number of segments. Evaluation of spatial and spectral localization of the target
      of interest was performed in simulation and phantom experiments, and was compared
      with the point resolved spectroscopy (PRESS) experiment with standard voxels. The
      selective excitation experiments demonstrated excellent spatial localization and
      a broad frequency response, although PRESS was superior in direct comparisons
      with respect to signal-to-noise ratio (SNR) and outer volume suppression.
      Extensive SNR variation was observed dependent on trajectory (8%-90%), with the
      preferred radial case producing approximately 40%-60% SNR of the PRESS case.
      Accelerated trajectories at R = 4 provided comparable artifact signal and target
      excitation accuracy compared with their nonaccelerated counterparts; however,
      further acceleration (R = 8) resulted in increased artifact (33% increase at R =
      8).

PMID- 21721041
TI  - In vivo iron quantification in collagenase-induced microbleeds in rat brain.
AB  - Brain microbleeds (BMB) are associated with chronic and acute cerebrovascular
      disease. Because BMB present in the brain is a source of potentially cytotoxic
      iron proportional to the volume of extravasated blood, BMB iron content is a
      potentially valuable biomarker both to assess tissue risk and small cerebral
      vessel health. We recently reported methods to quantify focal iron sources using
      phase images that were tested in phantoms and BMB in postmortem tissue. In this
      study, we applied our methods to small hemorrhagic lesions induced in the in vivo
      rat brain using bacterial collagenase. As expected by theory, measurements of
      geometric features in phase images correlated with lesion iron content measured
      by graphite furnace atomic absorption spectrometry. Iron content estimation
      following BMB in an in vivo rodent model could shed light on the role and
      temporal evolution of iron-mediated tissue damage and efficacy of potential
      treatments in cerebrovascular diseases associated with BMB.

PMID- 21721042
TI  - Uncertainties in the prevention and treatment of glucocorticoid-induced
      osteoporosis.
AB  - Much knowledge has accrued since the 2001 American College of Rheumatology (ACR)
      guidelines were published to assist clinicians in the prevention and treatment of
      glucocorticoid-induced osteoporosis (GIO). Therefore, the ACR undertook a
      comprehensive effort to review the literature and update the GIO guidelines
      [Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology
      2010 recommendations for the prevention and treatment of glucocorticoid-induced
      osteoporosis. Arthritis Care Res (Hoboken). 2010;62:1515-1526]. Herein, we review
      the new guidelines for JBMR readers, highlighting the changes introduced by the
      2010 publication. We discuss several patient scenarios for which the new
      treatment guidelines do not apply, or for which our committee interprets existing
      literature differently and suggests an alternative approach.

PMID- 21721043
TI  - Lithium decreases VEGF mRNA expression in leukocytes of healthy subjects and
      patients with bipolar disorder.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) is thought to be involved
      in the pathophysiology of mood disorders and the target of antidepressants. The
      aim of this study was to elucidate molecular effects of lithium on VEGF
      expression by using leukocytes of healthy subjects and patients with bipolar
      disorder. METHODS: Eight healthy male subjects participated in the first study.
      Lithium was prescribed for 2 weeks, enough to reach therapeutic serum
      concentration. Leukocyte counts and serum lithium concentrations were determined
      at baseline, at 1- and 2-week medication, and at 2 weeks after stopping
      medication. VEGF mRNA levels were also examined in nine lithium-treated bipolar
      patients and healthy controls in the second study. RESULTS: In the first study,
      leukocyte counts were significantly increased at 2 weeks compared with those at
      baseline and were normalized after 2 weeks. VEGF mRNA levels were significantly
      decreased at 2 weeks and after 2 weeks compared with those at baseline.
      Consistent with the first study, VEGF mRNA levels were significantly decreased in
      the lithium-treated bipolar patients compared with healthy controls. CONCLUSIONS:
      Our investigation suggests that VEGF mRNA expression may be useful as a
      peripheral marker of the effects of lithium.

PMID- 21721044
TI  - The Fear of Alzheimer's Disease Scale: a new measure designed to assess
      anticipatory dementia in older adults.
AB  - BACKGROUND: As the prevalence of Alzheimer's disease (AD) is rapidly increasing,
      apprehension about developing the degenerative disease (anticipatory dementia or
      fear of developing AD) has become a topic of interest. However, most studies of
      anticipatory dementia have utilized brief, nonvalidated measures to explore older
      adults' apprehension. As such, there is a significant need for a psychometrically
      sound instrument to measure this fear. METHODS: The current study utilized 101
      older adults ages 65 to 91 to develop and validate an important new scale, the
      Fear of Alzheimer's Disease Scale (FADS). Construct validity of the FADS was
      assessed with the State-Trait Anxiety Inventory-Form Y (STAI-Y). RESULTS:
      Analyses revealed a three-factor model for the FADS (i.e., General Fear, Physical
      Symptoms, and Catastrophic Attitude) and an alpha of 0.94 for the entire measure,
      indicating good internal consistency. The FADS demonstrated good construct
      validity, as it was significantly correlated with both the state and trait
      subscales of the STAI-Y, with the trait subscale yielding the highest
      correlation. CONCLUSION: The FADS is a reliable and valid instrument and is the
      first of its kind available to directly address anticipatory dementia among a
      general population of older adults.

PMID- 21721045
TI  - Biomarkers in dementia with Lewy bodies: a review.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) shares common clinical,
      neuropsychological and pathological features with other dementia subtypes, such
      as Alzheimer's disease (AD), making it difficult to differentiate in clinical
      practice. Despite the development of consensus diagnostic criteria, many cases
      are missed, and biomarkers to assist with diagnosis would represent important
      advances. Our aim was to review the literature to identify potential biomarkers
      that may distinguish DLB from other dementia subtypes, especially AD. METHOD: The
      literature search was performed using Medline up to October 2010 for imaging
      studies [single-photon emission computed tomography (SPECT), positron emission
      tomography (PET), magnetic resonance imaging (MRI) and amyloid imaging] and
      cerebrospinal fluid (CSF) markers in DLB. Individual articles were examined for
      additional references. The abstracts of the identified articles were read to
      determine the most relevant papers, which became the basis for this review.
      RESULTS: The most robust evidence available was for striatal dopamine transporter
      activity visualised by (123) I-labelled N-(3-fluoropropyl)-2beta-carbomethoxy
      3beta-(4-iodophenyl)nortropane ((123) I-FP-CIT) SPECT. Several other imaging
      techniques have also reported promising results, such as [(18) F]fluorodopa PET,
      which assesses nigrostriatal integrity; [(18) F]fluorodeoxyglucose PET, which
      assesses metabolic deficits; and meta-iodobenzylguanidine imaging, which assesses
      sympathetic cardiac denervation. Data from studies using CSF measures of amyloid
      and tau, occipital hypoperfusion on SPECT and preservation of medial temporal
      lobe structures on MRI suggest that they may offer less diagnostic
      discrimination. CONCLUSION: Several potential biomarkers have shown good
      diagnostic accuracy for DLB, but apart from FP-CIT SPECT, there is now a need for
      larger clinical multi-site studies, as well as for studies with pathological
      verification of diagnosis, before their use could be recommended for routine
      clinical practice.

PMID- 21721046
TI  - SymmRef: a flexible refinement method for symmetric multimers.
AB  - Symmetric protein complexes are abundant in the living cell. Predicting their
      atomic structure can shed light on the mechanism of many important biological
      processes. Symmetric docking methods aim to predict the structure of these
      complexes given the unbound structure of a single monomer, or its model. Symmetry
      constraints reduce the search-space of these methods and make the prediction
      easier compared to asymmetric protein-protein docking. However, the challenge of
      modeling the conformational changes that the monomer might undergo is a major
      obstacle. In this article, we present SymmRef, a novel method for refinement and
      reranking of symmetric docking solutions. The method models backbone and side
      chain movements and optimizes the rigid-body orientations of the monomers. The
      backbone movements are modeled by normal modes minimization and the conformations
      of the side-chains are modeled by selecting optimal rotamers. Since solved
      structures of symmetric multimers show asymmetric side-chain conformations, we do
      not use symmetry constraints in the side-chain optimization procedure. The
      refined models are re-ranked according to an energy score. We tested the method
      on a benchmark of unbound docking challenges. The results show that the method
      significantly improves the accuracy and the ranking of symmetric rigid docking
      solutions. SymmRef is available for download at http://
      bioinfo3d.cs.tau.ac.il/SymmRef/download.html.

PMID- 21721047
TI  - Molecular dynamics study of small molecule inhibitors of the Bcl-2 family.
AB  - We carried out docking and molecular dynamics simulations on ABT-737 and
      obatoclax, which are inhibitors of the Bcl-2 family of proteins. We modeled the
      binding mode of ABT-737 with Bcl-x(L) , Bcl-2, and Mcl-1 and examined their
      dynamical behavior. We found that the binding of the chlorobiphenyl end of ABT
      737 was quite stable across all three proteins. However, the phenylpiperazine
      linker group was dramatically more mobile in Mcl-1 compared to either Bcl-x(L) or
      Bcl-2. The S-phenyl group at the p4 binding site was well-anchored in Bcl-x(L)
      and Bcl-2 but was somewhat more mobile in Mcl-1 although the phenyl ring itself
      on average stayed close to the p4 binding site in Mcl-1. This greater mobility is
      likely due to the greater openness of the p3 and p4 binding sites on Mcl-1. The
      calculated binding free energies were consistent with the much weaker binding
      affinity of ABT-737 for Mcl-1. Obatoclax was predicted to bind at the p1 and p2
      binding sites of Mcl-1 and the binding mode was quite stable during the molecular
      dynamics simulation with Mcl-1 wrapping around the molecule. The modeled binding
      mode suggests that obatoclax is able to inhibit all three proteins because it
      makes use of the p1 and p2 binding sites alone, which is a fairly narrow groove
      in all three proteins unlike the p4 binding site, which is much broader in Mcl-1.

PMID- 21721048
TI  - A novel "open-form" structure of sortaseC from Streptococcus suis.

PMID- 21721051
TI  - Mesoporous TiO2-B microspheres with superior rate performance for lithium ion
      batteries.

PMID- 21721052
TI  - Magnetoresistance in an all-organic-based spin valve.

PMID- 21721053
TI  - Single-fiber-based hybridization of energy converters and storage units using
      graphene as electrodes.

PMID- 21721054
TI  - Tunable field-effect mobility utilizing mixed crystals of organic molecules.

PMID- 21721055
TI  - Self-wrinkling of UV-cured polymer films.

PMID- 21721056
TI  - Ambipolar oxide thin-film transistor.

PMID- 21721057
TI  - Nanofibrous lipid membranes capable of functionally immobilizing antibodies and
      capturing specific cells.

PMID- 21721058
TI  - Elucidation of lignin structure by quantitative 2D NMR.
AB  - Quick quantitative HSQC (QQ-HSQC) was applied to quantitative evaluation of
      different inter-unit linkages in an array of milled softwood and hardwood and
      technical lignins by using the guaiacyl C2 and syringyl C2-C6 signals as internal
      standards. The results were found to be highly reproducible and comparable with
      earlier literature reports. The advantage of QQ-HSQC NMR analysis of lignin is
      contemporary detection and quantification of lignin inter-unit linkages with a
      direct, non-destructive method requiring short acquisition times.

PMID- 21721059
TI  - Lewis base assisted Bronsted base catalysis: direct regioselective asymmetric
      vinylogous alkylation of allylic sulfones.
AB  - A Lewis base assisted Bronsted base catalysis (LBABB) strategy is applied for
      direct asymmetric vinylogous alkylation of allylic sulfones with Morita-Baylis
      Hillman (MBH) carbonates, in which a strong Bronsted base, tert-butoxy anion,
      generated in situ from a tertiary amine catalyst and MBH carbonate, is crucial in
      activating unstabilized nucleophiles. The gamma-regioselective alkylation
      products were obtained with good to excellent enantiomeric excess values when
      catalyzed by a modified cinchona alkaloid.

PMID- 21721060
TI  - In search of fullerene-based superacids: synthesis, X-ray structure, and DFT
      study of C60(C2F5)(5)H.
AB  - Simply super! The perfluoroalkylfullerene C(60)(C(2)F(5))(5) H is the first
      structurally characterized perfluoroalkylated fullerene-based acid and is also
      predicted to be the first gas-phase fullerene-based superacid.

PMID- 21721061
TI  - Cholinesterases inhibitory and antioxidant activities of Harpagophytum procumbens
      from in vitro systems.
AB  - A previous report showed that extracts of cell suspension and transformed root
      cultures of Harpagophytum procumbens (commonly known as Devil's claw), an African
      plant with high medicinal value, exhibit strong antiinflammatory characteristics.
      The present work tests the ability of extracts, phenylethanoid-containing
      fractions and the major phenylethanoid glycoside isolated from the Devil's claw
      cultures, to inhibit acetylcholinesterase and butyrylcholinesterase, and the
      antioxidant activity in iron-related systems (e.g. ferric-reducing antioxidant
      power and ferrous ion-chelating capacity). The results indicated that the
      phenylethanoid fractions may be attractive for various commercial purposes since
      they displayed significant cholinesterase inhibitory activity (even higher than
      that of pure galanthamine in the case of butyrylcholinesterase inhibition assay).
      Crude methanolic extracts from cell and hairy root cultures of Devil's claw
      exhibited strong ferrous ion-chelating capacity (1.5-2 times higher than pure
      butylated hydroxyanisole, used as positive standard).

PMID- 21721062
TI  - Morphological changes of the filamentous fungus Mucor mucedo and inhibition of
      chitin synthase activity induced by anethole.
AB  - trans-Anethole (anethole), a major component of anise oil, has a broad
      antimicrobial spectrum with antimicrobial activity relatively weaker than those
      of well-known antibiotics, and significantly enhances the antifungal activity of
      polygodial and dodecanol against the baker's yeast Saccharomyces cerevisiae and
      human pathogenic yeast Candida albicans. However, the antifungal mechanism of
      anethole is unresolved. Anethole demonstrated antifungal activity against the
      filamentous fungus, Mucor mucedo IFO 7684, accompanied by hyphal morphological
      changes such as swollen hyphae at the tips. Its minimum growth inhibitory
      concentration was 0.625 mM. A hyperosmotic condition (1.2 M sorbitol) restricted
      the induction of morphological changes, while hypoosmotic treatment (distilled
      water) induced bursting of hyphal tips and leakage of cytoplasmic constituents.
      Furthermore, anethole dose-dependently inhibited chitin synthase (CHS) activity
      in permeabilized hyphae in an uncompetitive manner. These results suggest that
      the morphological changes of M. mucedo could be explained by the fragility of
      cell walls caused by CHS inhibition.

PMID- 21721063
TI  - Correlation between the temperature dependence of intrinsic MR parameters and
      thermal dose measured by a rapid chemical shift imaging technique.
AB  - In order to investigate simultaneous MR temperature imaging and direct validation
      of tissue damage during thermal therapy, temperature-dependent signal changes in
      proton resonance frequency (PRF) shifts, R(2)* values, and T1-weighted amplitudes
      are measured from one technique in ex vivo tissue. Using a multigradient echo
      acquisition and the Stieglitz-McBride algorithm, the temperature sensitivity
      coefficients of these parameters are measured in each tissue at high
      spatiotemporal resolutions (1.6 x 1.6 x 4 mm 3,<= 5sec) at the range of 25-61 
      degrees C. Non-linear changes in MR parameters are examined and correlated with
      an Arrhenius rate dose model of thermal damage. Using logistic regression, the
      probability of changes in these parameters is calculated as a function of thermal
      dose to determine if changes correspond to thermal damage. Temperature
      sensitivity of R(2)* and, in some cases, T1-weighted amplitudes are statistically
      different before and after thermal damage occurred. Significant changes in the
      slopes of R(2)* as a function of temperature are observed. Logistic regression
      analysis shows that these changes could be accurately predicted using the
      Arrhenius rate dose model (Omega = 1.01 +/- 0.03), thereby showing that the
      changes in R(2)* could be direct markers of protein denaturation. Overall, by
      using a chemical shift imaging technique with simultaneous temperature
      estimation, R(2)* mapping and T1-W imaging, it is shown that changes in the
      sensitivity of R(2)* and, to a lesser degree, T1-W amplitudes are measured in ex
      vivo tissue when thermal damage is expected to occur. These changes could
      possibly be used for direct validation of thermal damage in contrast to model
      based predictions.

PMID- 21721064
TI  - Alteration of time perception in young and elderly people during jigsaw puzzle
      tasks with different complexities.
AB  - We investigated the relationship between time perception during tasks and
      subjective feelings in young and elderly people. Simple and complex jigsaw
      puzzles were given to healthy young and elderly subjects. The subjects were asked
      to estimate the time they had taken to complete the tasks after performing them.
      The ratio of the subjective to actual duration of time, the duration judgment
      ratio (DJR), and the relationship between the DJR and the subjective feelings
      during the tasks were analysed. The elderly group required a significantly longer
      time than the younger group for both tasks, and both elderly and young subjects
      estimated a longer time than the actual time to complete the tasks. The effect of
      the tasks on the DJR was significant, and the value was higher for the 24-piece
      than 54-piece task in both groups. The DJR was smaller in subjects with "much
      interest" than in those with "little interest" in the 24-piece task, but there
      was no difference in the 54-piece task. The results indicate that time perception
      was modulated by subjective feelings during the task, as well as by the age and
      task complexity. Because the goal and the result of the task may modulate time
      perception during it, time perception while actually performing the task may
      differ from that after completing it.

PMID- 21721065
TI  - Amphiphilic block copolymers from a direct and one-pot RAFT synthesis in water.
AB  - The syntheses of amphiphilic block copolymers are successfully performed in water
      by chain extension of hydrophilic macromolecules with styrene at 80  degrees C.
      The employed strategy is a one-pot procedure in which poly(acrylic acid),
      poly(methacrylic acid) or poly(methacrylic acid-co-poly(ethylene oxide) methyl
      ether methacrylate) macroRAFTs are first formed in water using 4-cyano-4
      thiothiopropylsulfanyl pentanoic acid (CTPPA) as a chain transfer agent. The
      resulting macroRAFTs are then directly used without further purification for the
      RAFT polymerization of styrene in water in the same reactor. This simple and
      straightforward strategy leads to a very good control of the resulting
      amphiphilic block copolymers.

PMID- 21721066
TI  - Improved in vitro development of cloned bovine embryos using S
      adenosylhomocysteine, a non-toxic epigenetic modifying reagent.
AB  - In this study, fibroblast cells were stably transfected with mouse POU5F1
      promoter-driven enhanced green fluorescent protein (EGFP) to investigate the
      effect of S-adenosylhomocysteine (SAH), the reversible non-toxic inhibitor of DNA
      methyltransferases (DNMTs), at different intervals post-fusion on in vitro
      development of cloned bovine embryos. Treatment with SAH for 12 hr resulted in
      54.6 +/- 7.7% blastocyst production, which was significantly greater than in
      vitro fertilized embryos (IVF: 37.2 +/- 2.7%), cloned embryos treated with SAH
      for 72 hr (31.0 +/- 7.6%), and control cloned embryos (34.6 +/- 3.6%). The
      fluorescence intensities of the EGFP-POU5F1 reporter gene at all intervals of SAH
      treatment, except of 72 hr, were significantly higher than control somatic cell
      nuclear transfers (SCNT) embryos. The intensity of DNA-methylation in cloned
      embryos treated with SAH for 48 hr was similar to that of IVF embryos, and was
      significantly lower than the other SCNT groups. The levels of H3K9 acetylation in
      all SCNT groups were significantly lower than IVF embryos. Real-time PCR analysis
      of gene expression revealed significantly higher expression of POU5F1 in cloned
      versus IVF blastocysts. Neither embryo production method (SCNT vs. IVF) nor the
      SAH treatment interval affected expression of the BCL2 gene. Cloned embryos at
      all intervals of SAH treatment, except for 24 hr, had significantly increased
      VEGF transcript compared to IVF and control SCNT embryos. It was suggested that
      the time interval of DNMT inhibition may have important consequences on different
      in vitro features of bovine SCNT, and the improving effects of DNMT inhibition on
      developmental competency of cloned embryos are restricted to a specific period of
      time preceding de novo methylation.

PMID- 21721067
TI  - Does apoptosis hold the key to long-term sperm storage mechanisms in vivo?

PMID- 21721068
TI  - The Relationship Between Weight Loss and Health-related Quality of Life in a
      Serbian Population.
AB  - We examined changes in weight-specific health-related quality of life (HRQOL) and
      the relation to weight loss in a Serbian population undergoing diet-induced
      weight loss treatment. HRQOL was assessed at intake and after 1 year using the
      Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. Study sample
      consists of 135 obese patients. After 1 year of diet therapy, patients
      experienced an average weight loss of ~12%, and significant improvements were
      noted in all IWQOL-Lite domains (Physical Function, Self-esteem, Sexual Life,
      Public Distress and Work). Amount of weight loss was closely linked to all
      domains (F = 27.49; p < 0.001), except Sexual Life (F = 2.08; p = 0.108). In
      patients with weight reductions of 5%-9.99%, there was a great improvement in
      physical function and self-esteem. In those with >=10% weight loss, there was
      improvement in all dimensions of IWQOL-Lite. With the prevalence of obesity
      rising worldwide, including in Serbia, the positive effects of weight loss on
      weight-specific HRQOL are encouraging.

PMID- 21721069
TI  - Trajectory compensation in an autoresonant trap mass spectrometer.
AB  - The auto-resonant trap mass spectrometer, ART-MS, utilizes electrostatic ion
      trapping within an anharmonic potential well. Ions are detected after mass
      selective trap ejection with auto-resonant driving employing only low-power rf
      electronics. We identify the major limiting factor in the mass resolution of
      these instruments. Whilst keeping in the spirit of maintaining a rapid scan rate,
      low cost, lightweight instrument, with minimal required machining tolerances, we
      introduce a method for much improving the mass resolutions of an ART-MS. The
      addition of two electrodes has enabled an improvement in the mass resolution by a
      factor of ~4. The scheme significantly reduces the effects of a finite sized trap
      and compensates for the influence of radial variation in natural oscillating
      frequencies within the trap. Compensation can be implemented with a wide range of
      designs and is not limited by the size of the trap.

PMID- 21721070
TI  - Star-D: lessons learned and future implications.

PMID- 21721071
TI  - Early patterns of symptom change signal remission with interpersonal
      psychotherapy for depressed adolescents.
AB  - BACKGROUND: This study examined whether reductions in depression symptoms at
      different time points over the course of therapy predict remission for depressed
      adolescents treated with interpersonal psychotherapy (IPT-A) or treatment as
      usual (TAU) delivered in school-based health clinics. METHODS: Participants were
      63 adolescents (ages 12-18) drawn from a randomized controlled clinical trial
      examining the effectiveness of IPT-A Mufson et al. [2004; Archives of General
      Psychiatry 61:577-584]. Adolescents were randomized to receive IPT-A or TAU
      delivered by school-based mental health clinicians. Assessments were completed at
      baseline and weeks 4, 8, 12, and 16 (or at early termination) and included the
      Hamilton Rating Scale for Depression (HRSD; Hamilton [1967; British Journal of
      Social and Clinical Psychology 6:278-2962]). RESULTS: Receiver operating
      characteristic analysis was used to identify the time point and degree of
      reduction in HRSD that best predicted remission (HRSD <7) at the end of the trial
      (week 16). Week 4 was the best time point for classifying adolescents as likely
      to remit or not likely to remit for both IPT-A and TAU. A 16.2% reduction in HRSD
      from baseline represented the best combined sensitivity and specificity in
      predicting week 16 remission status for adolescents treated with IPT-A. A 24.4%
      reduction in depressive symptoms represented the best combined sensitivity and
      specificity in predicting remission status for TAU. CONCLUSIONS: These findings
      provide preliminary evidence of one early marker of remission with IPT-A.
      Replication with larger samples would suggest that depressed adolescents who have
      not demonstrated at least a 16.2% reduction in their depressive symptoms after 4
      weeks of IPT-A may benefit from a change in the treatment plan.

PMID- 21721072
TI  - Changes in negative beliefs following three brief programs for facilitating
      recovery after assault.
AB  - BACKGROUND: This study examines whether changes in negative beliefs about
      oneself, others, and the world occur as a result of early intervention aimed at
      preventing the development of chronic PTSD and further explores whether changes
      in negative beliefs during early intervention mediate long-term changes in
      psychopathology and functioning. METHODS: Ninety recent female assault survivors
      were randomized to 4-week early intervention programs: brief cognitive behavioral
      intervention, weekly assessment, or supportive counseling (SC). Changes in
      negative beliefs were examined from preintervention to postintervention. RESULTS:
      Negative beliefs improved across interventions, with somewhat less benefit
      reported by participants receiving SC. As expected, before intervention more
      severe negative beliefs were associated with higher initial trauma reactions and
      these negative beliefs generally improved from preintervention to
      postintervention. Moreover, for the brief cognitive-behavioral intervention,
      changes in perceptions of self and one's safety mediated longer-term changes in
      trauma-related symptoms. CONCLUSIONS: The present results highlight the potential
      importance of changes in negative beliefs in long-term adjustment of recent
      assault survivors.

PMID- 21721073
TI  - Randomized controlled trial of Internet-delivered cognitive behavioral therapy
      for posttraumatic stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a severe and disabling
      condition and few receive appropriate care. Internet-based treatment of PTSD
      shows promise in reducing barriers to care and preliminary evidence suggests it
      is efficacious in treating symptoms of PTSD. METHODOLOGY: Forty-two individuals
      with a diagnosis of PTSD confirmed by clinician interview completed a randomized
      controlled comparison of Internet-based cognitive behavioral therapy (CBT) with a
      waitlist control condition. PRINCIPLE FINDINGS: Large pre- to posttreatment
      effect sizes (ESs) were found for the Treatment group on measures of PTSD
      symptoms, depression, anxiety, and disability. A small between-group ES was found
      for PTSD symptoms and moderate between-group ESs were found for depression,
      anxiety, and disability. CONCLUSIONS: Results provide preliminary support for
      Internet-based CBT as an efficacious treatment for individuals with a confirmed
      primary diagnosis of PTSD.

PMID- 21721074
TI  - Sustained, high transgene expression in liver with plasmid vectors using
      optimized promoter-enhancer combinations.
AB  - BACKGROUND: Plasmid-based gene therapy approaches often lack long-term transgene
      expression in vivo as a result of silencing or loss of the vector. One way to
      overcome these limitations is to combine nonsilenced promoters with strong
      enhancers. METHODS: In the present study, we combine murine or human
      cytomegalovirus (CMV)-derived enhancer elements with the human elongation factor
      1alpha (EF1alpha) promoter in a plasmid backbone devoid of potentially
      immunostimulating cytosine-guanine repeat sequences. Luciferase transgene
      activity was monitored in mouse liver after hydrodynamic plasmid delivery.
      RESULTS: Luciferase activity of a CMV-promoter driven plasmid rapidly declined
      within days, whereas the activity of the EF1alpha driven plasmid remained high
      for 2 weeks (murine enhancer) and detectable for > 80 days (human enhancer).
      Expression levels clearly correlated with higher plasmid copy number found in the
      liver at 2 months after gene delivery. Furthermore, we developed a novel
      synthetic CMV-EF1alpha hybrid promoter (SCEP) combining the high activity of CMV
      and sustained activity of EF1alpha promoter. The SCEP led to a constitutive three
      fold increase in expression levels compared to the EF1alpha promoter in vivo.
      CONCLUSIONS: This novel combination of enhancer and promoter element with
      optimized plasmid backbones will pave the way for more efficient nonviral
      approaches in gene therapy.

PMID- 21721075
TI  - Therapeutic ultrasound promotes plasmid DNA uptake by clathrin-mediated
      endocytosis.
AB  - BACKGROUND: Ultrasound (US) has been widely used to improve the efficiency of
      nonviral vector transfection. The mechanism of plasmid uptake is usually
      attributed to sonoporation, although there is not clear evidence for this
      attribution. Based on our previous results, we hypothesized that other
      mechanisms, such as endocytosis, could be involved in this process. METHODS:
      NIH3T3 cells were transfected with plasmid vector pEGFP-N3 (4.7 kb) using a
      therapeutic US without microbubbles. Bioeffects such as calcium influx, reactive
      oxygen species (ROS) generation and membrane potential alterations were accessed
      with fluorescent dyes in real-time by confocal microscopy after US insonation.
      Localization of labeled plasmid DNA in cells was also monitored with endocytosis
      markers using an immunofluorescence assay. RESULTS: US at 2 W/cm(2) with a duty
      cycle of 20% for 30 s resulted in approximately 40% transfection efficiency but,
      at 1 W/cm(2) , resulted in a very low level of transfection. Both the production
      of ROS and calcium influx were augmented during the insonation, although they
      were stopped soon after turning off US, with the exception of calcium influx with
      1 W/cm(2) . US also changed the cell membrane potential to the hyperpolarization
      state, which returned to the normal state soon after insonation. Labeled plasmids
      DNA could be co-localized with clathrin-mediated endocytosis marker but not with
      caveolin-1. CONCLUSIONS: The present data indicate that plasmid DNA uptake
      promoted by US should occur via clathrin-mediated endocytosis.

PMID- 21721076
TI  - Mechanisms of polyethylenimine-mediated DNA delivery: free carrier helps to
      overcome the barrier of cell-surface glycosaminoglycans.
AB  - BACKGROUND: Polyethylenimine (PEI) polyplexes mediate efficient gene transfer
      only at high +/- charge ratios at which free noncomplexed PEI is present. The
      excess of PEI gives polyplexes a positive surface charge that plays a role in
      polyplex binding on the cell membrane. Although positively charged PEI polyplexes
      are known to interact with anionic cell-surface glycosaminoglycans (GAGs), the
      exact role of free PEI in such interactions is unclear. METHODS: Chinese hamster
      ovary wild-type cells and mutants lacking cell-surface GAGs were transfected with
      marker genes using PEI polyplexes with and without free PEI. The total amount of
      cell-associated plasmid DNA (pDNA) delivered by polyplexes was determined by
      quantitative real-time PCR and transgene expression was determined using beta
      galactosidase and luciferase assays. RESULTS: Transfection activity of polyplexes
      without free PEI in cells expressing cell-surface GAGs was low even though pDNA
      was delivered to cells. In the absence of cell-surface GAGs, polyplexes without
      free PEI had high transfection efficacy. This indicates that the cell-surface
      GAGs inhibit transfection by purified polyplexes. PEI polyplexes with free
      carrier mediated transfection in both normal and GAG-deficient cells because free
      PEI overcomes the inhibitory effect of cell-surface GAGs on transfection. The
      intracellular elimination of pDNA was faster in the presence of GAGs and, despite
      improved transfection, free PEI reduced pDNA association with the cells.
      CONCLUSIONS: Free PEI is essential for minimizing the undesirable binding of
      polyplexes to cell-surface GAGs that have a negative impact on transfection. The
      same mechanism may be important in transfections with other polyplexes that
      require high charge ratios for transfection.

PMID- 21721078
TI  - Artificially induced protein-membrane anchorage with cholesterol-based
      recognition agents as a new therapeutic concept.

PMID- 21721080
TI  - Shuttle-mediated drug delivery to the brain.
AB  - Advances in the field of shuttle-mediated drug delivery have been made in the
      last decade; however, the treatment of brain disorders still remains a great
      challenge because of the presence of the blood-brain barrier (BBB), a structure
      that limits the access of drugs to their site of action in the central nervous
      system. Several strategies have been proposed to enhance the transport of drugs
      across the BBB. In this Review, we focus on the vector-mediated approach, in
      which a drug is coupled to a molecule (shuttle) that has the ability to cross the
      BBB and deliver the drug to the brain.

PMID- 21721081
TI  - Quantitative 3D analysis of nitric oxide diffusion in a 3D artery model using
      sensor particles.

PMID- 21721082
TI  - Tunable carbonyl ylide reactions: selective synthesis of dihydrofurans and
      dihydrobenzoxepines.

PMID- 21721083
TI  - A desulfatation-oxidation cascade activates coumarin-based cross-linkers in the
      wound reaction of the giant unicellular alga Dasycladus vermicularis.

PMID- 21721084
TI  - Highly selective fluorescent probe for vicinal-dithiol-containing proteins and in
      situ imaging in living cells.

PMID- 21721085
TI  - High and highly anisotropic proton conductivity in organic molecular porous
      materials.

PMID- 21721086
TI  - Multifunctional nanoparticles for targeted chemophotothermal treatment of cancer
      cells.

PMID- 21721087
TI  - Macrocyclization of oxetane building blocks with diazocarbonyl derivatives under
      rhodium(II) catalysis.

PMID- 21721088
TI  - Palladium-catalyzed direct synthesis of organoboronic acids.

PMID- 21721090
TI  - Organocatalytic hydroacylation of unactivated alkenes.
AB  - N-Heterocyclic carbenes interact with aldehydes to generate the Breslow
      intermediate, a rendering of the prototypical electrophile into a nucleophile
      (umpolung). Recent work has indicated that these intermediates may also add to
      simple, unpolarized alkenes. The use of a chiral precatalyst leads to the
      generation of the derived adducts with high yields and very high selectivities.

PMID- 21721091
TI  - Nanostructured immunosensor for attomolar detection of cancer biomarker
      interleukin-8 using massively labeled superparamagnetic particles.

PMID- 21721092
TI  - Lewis acid promoted benzylic cross-couplings of pyridines with aryl bromides.

PMID- 21721093
TI  - The discovery of 5-formylcytosine in embryonic stem cell DNA.

PMID- 21721097
TI  - Accurate quantum dynamics study on the resonance decay of vinylidene.

PMID- 21721098
TI  - The challenge of caring for arthritis at the end of life.

PMID- 21721099
TI  - Dynamic factors controlling carrier anchoring on vascular cells.
AB  - This article reviews experimental and modeling methods for determining the
      critical roles played by the various factors that control nanocarrier drug
      delivery to vascular endothelial cells.

PMID- 21721100
TI  - Magnetic nanoparticles for targeted vascular delivery.
AB  - Magnetic targeting has shown promise to improve the efficacy and safety of
      different classes of therapeutic agents by enabling their active guidance to the
      site of disease and minimizing dissemination to nontarget tissues. However, its
      translation into clinic has proven difficult because of inherent limitations of
      traditional approaches inapplicable for deep tissue targeting in human subjects
      and a need for developing well-characterized and fully biocompatible magnetic
      carrier formulations. A novel magnetic targeting scheme based on the magnetizing
      effect of deep-penetrating uniform fields is presented as an example of a
      strategy providing a potentially clinically viable solution for preventing injury
      triggered reobstruction of stented blood vessels (in-stent restenosis). The
      design of optimized magnetic carrier formulations and experimental results
      showing the feasibility of uniform field-controlled targeting for site-specific
      vascular delivery of small-molecule pharmaceuticals, biotherapeutics, and cells
      are discussed in the context of antirestenotic therapy. The versatility of this
      approach applicable to different classes of therapeutic agents exerting their
      antirestenotic effects through distinct mechanisms prompts exploring the utility
      of uniform field-mediated magnetic stent targeting for combination therapies with
      enhanced efficiencies and improved safety profiles. Additional improvements in
      terms of site specificity and protracted carrier retention at the site of injury
      may be expected from the development and use of magnetic carriers exhibiting
      affinity for arterial wall-specific antigens.

PMID- 21721101
TI  - Targeted therapeutics and nanodevices for vascular drug delivery: quo vadis?
AB  - This issue of the journal is dedicated to targeted delivery of therapeutics in
      the vasculature, an approach that holds promise to optimize treatment of diverse
      pathological conditions ranging from ischemia and tumor growth to metabolic and
      genetic diseases. From the standpoint of drug delivery, circulation system
      represents the natural route to the targets, whereas its components (blood and
      vascular cells) represent targets, carriers or barriers for drug delivery.
      Diverse nanodevices and targeted therapeutic agents that are designed and tested
      in animal and early clinical studies to achieve optimal and precise
      spatiotemporal control of the pharmacokinetics, destination, metabolism and
      effect of pharmacological agents will be discussed in this introductory essay and
      subsequent critical reviews in this series.

PMID- 21721102
TI  - Lung vascular targeting through inhalation delivery: insight from filamentous
      viruses and other shapes.
AB  - Systemic delivery of therapeutic agents via inhalation of particulates remains an
      attractive, noninvasive means of administration due to the possibilities of high
      bioavailability and high patient compliance. Optimization of particle shapes and
      particle properties for deep lung deposition after inhalation continues to be one
      of the key challenges. Here, we review several aspects of nanoparticle design for
      deep lung deposition as well as the nature and extent of translocation through
      the air-blood barrier for local or systemic vascular targeting. We describe
      filamentous influenza virus in comparison to worm-like "filomicelle" polymers as
      one example of a nature inspired design.

PMID- 21721103
TI  - Novel platforms for vascular carriers with controlled geometry.
AB  - The first-generation platforms for vascular drug delivery adopted spherical
      morphologies. These carriers relied primarily on the size dependence of the
      enhanced permeability and retention effect to passively target vasculature,
      resulting in inefficient delivery due to significant variation in endothelial
      permeability. Enhanced delivery typically requires active targeting via receptor
      mediated endocytosis by surface conjugation of targeting ligands. However,
      vascular carriers (VCs) still face numerous challenges en route to reaching their
      targets before delivery. The control of carrier shape offers opportunities to
      overcome in vivo barriers and enhance vascular drug delivery. Geometric features
      influence the ability of carrier particles to navigate physiological flow
      patterns, evade biological clearance mechanisms, sustain circulation, adhere to
      the vascular surface, and finally transport across or internalize into the
      endothelium. Although previous formulation strategies limited the fabrication of
      nonspherical carriers, numerous recent advances in both top-down and bottom-up
      fabrication techniques have enabled shape modulation as a key design element. As
      part of a series on vascular drug delivery, this review focuses on recent
      developments in novel vascular platforms with controlled geometry that enhance or
      modulate delivery functions. Starting with an overview of controlled geometry
      platforms, we review their shape-dependent functional characteristics for each
      stage of their vascular journey in vivo. We sequentially explore carrier
      geometries that evade reticuloendothelial system uptake, display enhanced
      circulation persistence and margination dynamics in flow, encourage adhesion to
      the vascular surface or extravasation through endothelium, and impact
      extravascular transport and cell internalization. The eventual biodistribution of
      VCs results from the culmination of their successive navigation of all these
      barriers and is profoundly influenced by their morphology. To enhance delivery
      efficacy, carrier designs synergistically combining controlled geometry with
      standard drug delivery strategies such as targeting moieties, surface
      decorations, and bulk material properties are discussed. Finally, we speculate on
      possibilities for innovation, harnessing shape as a design parameter for the next
      generation of vascular drug delivery platforms.

PMID- 21721104
TI  - Reduced expression of transforming growth factor-beta1 and correlated elevation
      of interleukin-17 and interferon-gamma in pediatric patients with chronic primary
      immune thrombocytopenia (ITP).
AB  - BACKGROUND: Dysregulated T helper (Th) cells are considered important in the
      pathophysiology of chronic primary immune thrombocytopenia (ITP). The present
      study investigated whether levels of Th cytokines in pediatric patients with
      chronic ITP were different compared with healthy controls. PROCEDURES: Fifty
      seven pediatric patients with chronic ITP and 28 healthy controls were enrolled.
      Patients were divided into three groups based on their platelet counts at the
      time of the study: (i) active disease <50 * 10(9) /l (n = 23), (ii) stable
      disease 50-150 * 10(9) /l (n = 23), and (iii) in remission >150 * 10(9) /l (n =
      11). Plasma concentration of Th1 [interferon gamma (INF-gamma), interleukin 2 (IL
      2)], Th2 (IL-4, IL-10), Th3 [transforming growth factor-beta1 (TGF-beta1)], and
      Th17 (IL-17) cytokines were investigated by enzyme-linked immunosorbent assay.
      RESULTS: IFN-gamma was increased in patients with active (P < 0.001) and stable
      disease (P = 0.026) when compared with controls. The IL-17 level was
      significantly higher in all of the 3 patient groups. In addition, there was a
      positive correlation between IL-17 and IFN-gamma levels in chronic ITP patients
      (r = 0.640, P < 0.001). Reduced TGF-beta1 expression was observed in patients
      with active (P < 0.001) and stable disease (P = 0.001) in comparison with
      controls. Moreover, TGF-beta1 level in patients was positively correlated with
      the platelet count (r = 0.355, P = 0.007). CONCLUSIONS: Elevation of IL-17 and
      IFN-gamma may be an important dysregulation of cellular immunity in pediatric
      patients with chronic ITP. The disease activity is associated with reduced
      production of TGF-beta1.

PMID- 21721105
TI  - Transient partial response to sorafenib treatment in an adolescent patient with
      MEN2B syndrome and end-stage medullary thyroid carcinoma.
AB  - Metastatic medullary thyroid carcinoma (MTC) is an aggressive malignancy with an
      extremely poor prognosis. Currently no effective conventional systemic therapies
      exist to treat pediatric MTC. We describe an adolescent female with newly
      diagnosed MEN2B syndrome who presented with advanced stage metastatic MTC and
      demonstrated a partial transient response to sorafenib monotherapy. This clinical
      result supports further research into the use of sorafenib in the treatment of
      pediatric MTC.

PMID- 21721106
TI  - Klinefelter syndrome and neuroblastoma.

PMID- 21721107
TI  - Neutropenia in infants with hemolytic disease of the newborn.
AB  - BACKGROUND: This study examined the incidence, outcome and risk factors of
      neutropenia in infants with hemolytic disease of the newborn (HDN). METHODS: A
      retrospective chart review was performed on infants with HDN. RESULTS: Of 69
      evaluable infants, 45% developed neutropenia. Only one infectious complication
      was recorded. In most instances the neutropenia resolved spontaneously, but in
      seven infants it persisted for a median of 397 days. Males were at higher risk
      for developing neutropenia, but severity of HDN, antibody specificity, or therapy
      were not significant risk factors. CONCLUSIONS: Neutropenia is a common feature
      of HDN, regardless of severity of disease, treatment received, or antibody
      specificity.

PMID- 21721108
TI  - For the issue dedicated to the 150th anniversary of chemistry at the University
      of Tokyo.

PMID- 21721109
TI  - In commemoration of the 150th anniversary of the Department of Chemistry, School
      of Science, the University of Tokyo--its past and future.

PMID- 21721113
TI  - Clinical predictors of high risk histopathology in retinoblastoma.
AB  - BACKGROUND: Previous studies show that clinical features at presentation, in
      retinoblastoma patients, like glaucoma and neovascularization of iris are
      associated with a higher incidence of high risk histopathology findings (HRF) in
      enucleated eyes. Herein, we analyze association between clinical features at time
      of enucleation and occurrence of HRF including invasion of anterior chamber,
      iris, ciliary body, choroid (massive), sclera, extrascleral tissue, optic nerve
      beyond lamina cribrosa, and optic nerve cut end, in a large series of eyes
      enucleated for retinoblastoma. PROCEDURE: We retrospectively studied demographic,
      clinical, and histopathology findings in all retinoblastoma patients who
      underwent primary enucleation at our center, over a 5 years duration. Statistical
      analysis was done to find any association between clinical features at
      presentation and the presence of HRF. RESULTS: Three hundred twenty-six eyes were
      studied. Median age of presentation was 2 years. Glaucoma was the most common
      clinical finding at presentation apart from leucocoria. Out of 326 enucleated
      eyes, 28 (8.6%) had extrascleral and/or optic nerve transection invasion. Among
      remaining 298 eyes, with completely resected tumor, 115 (38.6%) had massive
      choroidal invasion, 54 (17%) had retrolaminar optic nerve invasion, and 24 (7%),
      29 (9%), and 23(7%) had anterior chamber, iris, and ciliary body invasion,
      respectively. Age more than 2 years, lag period more than 3 months, hyphema,
      pseudohypopyon, staphyloma, and orbital cellulitis were associated with
      occurrence of three or more HRF on univariate analysis. CONCLUSIONS: Clinical
      variables including older age, longer lag period, hyphema, pseudohypopyon,
      staphyloma, and orbital cellulitis were strongly associated with occurrence of
      HRF in this study.

PMID- 21721112
TI  - Neuropsychological outcomes of standard risk and high risk patients treated for
      acute lymphoblastic leukemia on Dana-Farber ALL consortium protocol 95-01 at 5
      years post-diagnosis.
AB  - BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) as High Risk
      (HR) patients may be more vulnerable to neurocognitive late effects because of
      the greater intensity of their therapy. We compared neuropsychological outcomes
      in children treated for Standard Risk (SR) or HR ALL on Dana-Farber Cancer
      Institute (DFCI) Consortium ALL Protocol 95-01. We also evaluated their
      performance relative to normative expectations. PROCEDURE: Between 1996 and 2000,
      498 children with newly diagnosed ALL were treated on Protocol 95-01, 298 of whom
      were eligible for neuropsychological follow-up. A feature of this protocol was
      modification of risk group criteria to treat more children as SR rather than HR
      patients, intended to minimize toxicities. Testing was completed at a median of
      5.3 years post-diagnosis for 211 patients (70.8%; ages 6-25 years; 45.5% male;
      40% HR), all of whom were in continuous complete remission. RESULTS: Test scores
      for both groups were generally at or above normative expectation, with the
      exception of verbal working memory, processing complex visual information, and
      parent ratings of metacognitive skills. After adjusting for covariates, the SR
      group performed better on measures of IQ and academic achievement, working memory
      and visual learning. Effect sizes, however, were only in the small to moderate
      range. CONCLUSIONS: HR patients exhibited neuropsychological deficits relative to
      SR patients, though the differences were modest in degree. Modification of the
      risk group criteria to treat more children on the SR protocol therefore likely
      afforded some benefit in terms of neurocognitive late effects.

PMID- 21721114
TI  - Incidence, risk factors, and outcome of pneumatosis intestinalis in pediatric
      stem cell transplant recipients.
AB  - BACKGROUND: Pneumatosis Intestinalis (PI) is a rare complication following
      hematopoietic stem cell transplant (HSCT). We sought to assess the incidence,
      risk factors, and outcome associated with PI. PROCEDURE: We retrospectively
      reviewed the incidence of PI among 178 patients who underwent allogeneic HSCT
      between September 1999 and February 2010. RESULTS: Eighteen of 178 children
      (10.1%) who received allogeneic HSCT developed PI at a median of 94 days (range,
      11-1169) after transplant. All patients presented with either abdominal pain or
      distention, and half of the patients had free air on radiographs. Patients who
      developed PI had a significantly higher proportion of acute (83% vs. 44%, P =
      0.002) and chronic graft versus host disease (GVHD; 56% vs. 18%, P < 0.001). Only
      39% of patients with PI had GVHD involving the gasterointestinal track. All
      patients were managed conservatively without surgery. Transplant related
      mortality (TRM) was significantly higher in patients who developed PI compared to
      those who did not (OR 4.3, 95% CI: 1.3-13.1; P = 0.007), but no deaths were
      attributable to PI. CONCLUSIONS: We conclude that PI is a common complication
      associated with treatment of GVHD after HSCT, and patients who develop PI
      experience higher TRM. Patients who develop PI should be managed medically.

PMID- 21721115
TI  - Amelioration of experimental autoimmune myasthenia gravis rats by blood
      purification treatment using 4-mercaptoethylpyridine-based adsorbent.
AB  - The role of immunoadsorption therapy is well established in the management of
      myasthenia gravis (MG), an autoimmune disorder characterized by muscle weakness
      and caused by circulating IgG antibodies with specificity against the
      acetylcholine receptor. Conventional immunoadsorbents that employ recombinant
      protein A as immobilized ligand suffer from the drawbacks of high cost and low
      stability. The objective of this work is to assess the safety and efficacy of a
      synthetic adsorbent for treating MG. Adsorption columns were prepared from a
      Sepharose-based adsorbent coupled to 4-mercaptoethylpyridine (MEP), which acted
      as immobilized ligands. Animal model of experimental autoimmune MG (EAMG) using
      Lewis rats was developed and treated by whole blood perfusion. The results showed
      that the treatments provided a significant amelioration of clinical weakness for
      EAMG rats, with clinic score decreasing from 2.08 +/- 0.38 to 1.25 +/- 0.27.
      After a treatment session of about 1.5 h, blood cell counts were not
      significantly changed. Serum levels of total IgG and acetylcholine receptor
      antibody were reduced by 37.1 +/- 6.5% and 35.6 +/- 8.6%, respectively. In
      addition, reduction in complement components C3 (47.1 +/- 6.7%), C4 (34.3 +/-
      3.4%), inflammatory cytokines interleukin-17 (10.4 +/- 2.7%), and tumor necrosis
      factor-alpha (8.2 +/- 3.1%) were also observed. This study demonstrated that MEP
      based adsorbent not only removed pathogenic autoantibodies directly from the
      blood as with protein A adsorbents but also modulated cellular immunity through
      removal of complement components and related proinflammatory cytokines, thereby
      providing a potentially superior strategy for the treatment of MG.

PMID- 21721116
TI  - Thermoresponsive poly(N-isopropylacrylamide)-g-methylcellulose hydrogel as a
      three-dimensional extracellular matrix for cartilage-engineered applications.
AB  - Recent advances in tissue engineering and regenerative medicine fields can offer
      alternative solutions to the existing techniques for cartilage repair. In this
      context, a variety of materials has been proposed, and the injectable hydrogels
      are among the most promising alternatives. The aim of this work is to explore the
      ability of poly(N-isopropylacrylamide)-g-methylcellulose (PNIPAAm-g-MC)
      thermoreversible hydrogel as a three-dimensional support for cell encapsulation
      toward the regeneration of articular cartilage through a tissue engineering
      approach. The PNIPAAm-g-MC copolymer was effectively obtained using ammonium
      persulfate and N,N,N',N'-tetramethylethylenediamine as initiator as confirmed by
      Fourier transform infrared spectroscopy and (1) H NMR results. The copolymer
      showed to be temperature responsive, becoming a gel at temperatures above its
      lower critical solution temperature (~ 32  degrees C) while turning into a liquid
      below it. Results obtained from the MTS test showed that extracts of the hydrogel
      were clearly noncytotoxic to L929 fibroblast cells. ATDC5 cells, a murine
      chondrogenic cell line, were used as the in vitro model for this study; they were
      encapsulated at high cell density within the hydrogel and cultured for up to 28
      days. PNIPAAm-g-MC did not affect the cell viability and proliferation, as
      indicated by both MTS and DNA assays. The results also revealed an increase in
      synthesis of glycosoaminoglycans within culture time measured by the
      dimethylmethylene blue quantification assay. These results suggest the viability
      of using PNIPAAm-g-MC thermoresponsive hydrogel as a three-dimensional scaffold
      for cartilage tissue engineering using minimal-invasive strategies.

PMID- 21721117
TI  - In vivo comparative biokinetics and biocompatibility of titanium and zirconium
      microparticles.
AB  - Titanium and zirconium are biomaterials that present a layer of titanium dioxide
      (TiO(2)) or zirconium dioxide (ZrO(2)). As a result of corrosion, microparticles
      can be released into the bioenvironment, and their effect on tissues is seemingly
      associated with differences in the physicochemical properties of these metals.
      The aim of this study was to perform a long-term evaluation of the distribution,
      destination, and potential risk of TiO(2) and ZrO(2) microparticles that might
      result from the corrosion process. Wistar rats were i.p. injected with an equal
      dose of either TiO(2) or ZrO(2) suspension. The following end-points were
      evaluated at 3, 6, and 18 months: (a) the presence of particles in blood cells
      and liver and lung tissue, (b) Ti and Zr deposit quantitation, (c) oxidant
      antioxidant balance in tissues, and (d) O(2)(-) generation in alveolar
      macrophages. Ti and Zr particles were detected in blood mononuclear cells and in
      organ parenchyma. At equal doses and times postadministration, Ti content in
      organs was consistently higher than Zr content. Ti elicited a significant
      increase in O(2)(-) generation in the lung compared to Zr. The consumption of
      antioxidant enzymes was greater in the Ti than in the Zr group. The present study
      shows that the biokinetics of TiO(2) and ZrO(2) depends on particle size, shape,
      and/or crystal structure.

PMID- 21721118
TI  - Influence of processing parameters on pore structure of 3D porous chitosan
      alginate polyelectrolyte complex scaffolds.
AB  - Fabrication of porous polymeric scaffolds with controlled structure can be
      challenging. In this study, we investigated the influence of key experimental
      parameters on the structures and mechanical properties of resultant porous
      chitosan-alginate (CA) polyelectrolyte complex (PEC) scaffolds, and on
      proliferation of MG-63 osteoblast-like cells, targeted at bone tissue
      engineering. We demonstrated that the porous structure is largely affected by the
      solution viscosity, which can be regulated by the acetic acid and alginate
      concentrations. We found that the CA PEC solutions with viscosity below 300 Pa.s
      yielded scaffolds of uniform pore structure and that more neutral pH promoted
      more complete complexation of chitosan and alginate, yielding stiffer scaffolds.
      CA PEC scaffolds produced from solutions with viscosities below 300 Pa.s also
      showed enhanced cell proliferation compared with other samples. By controlling
      the key experimental parameters identified in this study, CA PEC scaffolds of
      different structures can be made to suit various tissue engineering applications.

PMID- 21721119
TI  - The paratympanic organ: a barometer and altimeter in the middle ear of birds?
AB  - A century has passed since the discovery of the paratympanic organ (PTO), a
      mechanoreceptive sense organ in the middle ear of birds and other tetrapods. This
      luminal organ contains a sensory epithelium with typical mechanosensory hair
      cells and may function as a barometer and altimeter. The organ is arguably the
      most neglected sense organ in living tetrapods. The PTO is believed to be
      homologous to a lateral line sense organ, the spiracular sense organ of
      nonteleostean fishes. Our review summarizes the current state of knowledge of the
      PTO and draws attention to the astounding lack of information about the unique
      and largely unexplored sensory modality of barometric perception.

PMID- 21721120
TI  - Simultaneous determination of cyadox and its metabolites in plasma by high
      performance liquid chromatography tandem mass spectrometry.
AB  - Cyadox is a novel antimicrobial growth-promoter of the quinoxalines. For food
      safety and pharmacokinetic studies, a convenient, sensitive and reproducible LC
      ESI-MS/MS method was developed for the simultaneous determination of cyadox and
      its major metabolites, quinoxaline-2-carboxylic acid, 1,4-bisdesoxycyadox, cyadox
      1-monoxide and cyadox-4-monoxide in chicken plasma. Plasma sample was subjected
      to a simple deproteinisation with acetonitrile. Analysis was performed on a C18
      column by detection with mass spectrometry in multiple reaction monitoring mode.
      A gradient elution program with 0.2% formic acid, methanol and acetonitrile was
      performed at a flow rate of 0.2 mL/min. The decision limits (CCalphas) of five
      analytes in plasma ranged from 1.0 to 4.0 MUg/L, and the detection capabilities
      (CCbetas) were <10 MUg/L. Acceptable precision and accuracy were obtained for
      concentrations over the standard curve range. The extraction recoveries of five
      analytes were between 87.4 and 93.9% in plasma at the spiked levels of 5 (10)-200
      MUg/L with the relative standard deviations <10% for each analyte. The developed
      method demonstrated a satisfactory applicability in real plasma samples. 

PMID- 21721121
TI  - Counter-current chromatographic method for preparative scale isolation of
      picrosides from traditional Chinese medicine Picrorhiza scrophulariiflora.
AB  - Apocynin, androsin, together with picroside I, II and III from crude extracts of
      Picrorhiza scrophulariiflora were isolated by means of high-speed counter-current
      chromatography (CCC) combining elution-extrusion (EE) and cycling-elution (CE)
      approach. The EECCC took full advantages of the liquid nature of the stationary
      phase for a complete sample recovery and extended the solute hydrophobicity
      window, while CECCC showed its unique advantage in achieving effective separation
      of special compounds through preventing stationary phase loss. In the present
      work, the biphasic liquid system composed of n-hexane/ethyl
      acetate/methanol/water (1:2:1:2, v/v/v/v) was used for separation of apocynin and
      androsin, ethyl acetate/n-butanol/water/formic acid (4:1:5:0.005, v/v/v/v) for
      picroside I, II and III. However, due to the extremely similar K values (K1 /K2
      ~1.2), picroside I and III were always eluted together by several biphasic
      solvent systems. In this case, the CECCC exhibited great superiority and baseline
      separated in the sixth cycle using ethyl acetate/water (1:1, v/v) as biphasic
      liquid system. Each fraction was analyzed by UPLC-UV and ESI-MS analysis, and
      identified by comparing with the data of reference substances. Compared with
      classical elution, the combination of EE and CE approach exhibits strong
      separation efficiency and great potential to be a high-throughput separation
      technique in the case of complex samples. 

PMID- 21721122
TI  - Evaluation of matrix effects in analysis of estrogen using liquid chromatography
      tandem mass spectrometry.
AB  - Matrix effects of different biological samples, including phosphate-buffered
      saline-bovine serum albumin (PBS-BSA), gelded horse serum, mouse serum, and mouse
      brain, were investigated for the determination of 17alpha- and beta-estradiol
      using derivatization with dansyl chloride prior to LC-MS/MS. Matrix effects were
      evaluated based on the slopes of regression lines plotted from results obtained
      in biological matrices versus pure standard solutions. Such plots indicate the
      enhancement or suppression of signal based on the presence of a particular
      biological fluid for a particular method. The matrix effects from PBS-BSA were
      similar to those of mouse serum. In contrast, analyses performed from horse serum
      and mouse brain yielded significant ion suppression, especially for 17beta
      estradiol. Precipitation during derivatization was observed when pre-concentrated
      samples were processed with ethyl acetate as an extraction solvent. This was
      overcome with the use of methyl tert-butyl ether; however, matrix effects from
      this preparation were still present, evidenced by signal suppression and poor
      linearity in the standard curve. This work affirms that caution should be taken
      in the transfer of methods for use with different biological matrices, especially
      in the case where surrogate matrices are necessary for calibration purposes. 

PMID- 21721123
TI  - Computational study of the relationship between the flow resistance and the
      microscopic structure of polymer monoliths.
AB  - The present article reports on a numerical study of the permeability and flow
      resistance of ordered and random-structured polymer monolith mimics with
      different structures. Comparing the permeability of the different monolith
      structures with the same domain size and the same external porosity, it is found
      that the larger the degree of globule clustering, the lower is the resulting
      permeability. More or less independently of the external porosity, a 40% decrease
      in permeability is observed when comparing a purely cylindrical branch-type
      skeleton with a strongly clustered globular skeleton with the same external
      porosity. Correlations allowing to estimate the flow resistance as a function of
      the external porosity are presented for each considered degree of globule
      clustering. 

PMID- 21721124
TI  - Optimization of micro-HPLC peak focusing for the detection and quantification of
      low hepcidin concentrations.
AB  - Micro-high-performance liquid chromatography is a miniaturized, economic and
      ecological chromatographic system allowing the use of reduced size
      chromatographic columns. Coupled with electrospray ionization tandem mass
      spectrometry, this technique can be used to detect and quantify low
      concentrations of peptides. In this study, hepcidin was used as the model
      compound and analysed using octadecylsilica stationary phase by means of a
      gradient elution mode at a flow rate of 4 MUL/min. Several parameters were
      studied to optimize peak focusing. Using the methodology of experimental design,
      the mobile-phase gradient conditions and the sample composition were optimized in
      order to maximize the sensitivity and minimize retention time. Stability of the
      target peptide in solution was also demonstrated. 

PMID- 21721125
TI  - Hydrophilic diol monolith for the preparation of immuno-sorbents at reduced
      nonspecific interactions.
AB  - A polar organic polymer monolith (M1) was introduced for performing
      immunoaffinity chromatography (IAC) at reduced nonspecific interactions. The M1
      monolith was prepared by the in situ polymerization of glyceryl methacrylate
      (GMM) and pentaerythritol triacrylate (PETA). Through its surface diol groups, M1
      provided the functionalities to immobilize antibodies. Anti-haptoglobin antibody
      was used as the model antibody to study the overall behavior of the immuno
      monolith M1 in terms of its binding to the antigen and to evaluate its
      nonspecific binding with other proteins, especially the high-abundance human
      serum proteins. To better assess the suitability of M1 for IAC, other immuno
      monoliths were prepared and compared with the immuno monolith M1. Two monoliths
      were of the traditional ones: copolymers of (i) glycidyl methacrylate and
      ethylene glycol dimethacrylate (EDMA) and (ii) GMM and EDMA, referred to as M2
      and M3, respectively. A fourth monolith involving the copolymerization of N-(3
      aminopropyl)methacrylamide hydrochloride and EDMA (M4) was introduced to allow
      the site-directed immobilization of antibodies. Owing to its hydroxyl groups, the
      M1 exhibited negligible nonspecific hydrophobic interactions with proteins. On
      the other hand, M4 exhibited extensive electrostatic interactions, while the M2
      and to a lesser extent M3 exhibited hydrophobic interactions. 

PMID- 21721126
TI  - Highly selective uptake and release of charged molecules by pH-responsive
      polydopamine microcapsules.
AB  - A systematic study of the permeation of small molecules through Pdop
      microcapsules is reported. The zwitterionic Pdop microcapsules are prepared by
      oxidative polymerization of dopamine on polystyrene microspheres followed by core
      removal with THF. Rhodamine 6G, methyl orange and alizarin red are chosen as
      differently charged probing dyes. The loading amount is affected by pH and dye
      concentration. Highly selective and unidirectional uptake and release of charged
      molecules through Pdop microcapsules can be achieved by controlling pH value: at
      low pH, the Pdop particles incorporate cationic dye (rhodamine 6G); at high pH,
      they incorporate anionic dyes (methyl orange and alizarin red). In each case, the
      uptake is highly selective.

PMID- 21721127
TI  - Stem cell culture engineering - process scale up and beyond.
AB  - Advances in stem cell research and recent work on clinical trials employing stem
      cells have heightened the prospect of stem cell applications in regenerative
      medicine. The eventual clinical application of stem cells will require
      transforming cell production from laboratory practices to robust processes. Most
      stem cell applications will require extensive ex vivo handling of cells, from
      isolation, cultivation, and directed differentiation to product cell separation,
      cell derivation, and final formulation. Some applications require large
      quantities of cells in each defined batch for clinical use in multiple patients;
      others may be for autologous use and require only small-scale operations. All
      share a common requirement: the production must be robust and generate cell
      products of consistent quality. Unlike the established manufacturing process of
      recombinant protein biologics, stem cell applications will likely see greater
      variability in their cell source and more fluctuations in product quality.
      Nevertheless, in devising stem cell-based bioprocesses, much insight could be
      gained from the manufacturing of biological materials, including recombinant
      proteins and anti-viral vaccines. The key to process robustness is thus not only
      the control of traditional process chemical and physical variables, but also the
      sustenance of cells in the desired potency or differentiation state through
      controlling non-traditional variables, such as signaling pathway modulators.

PMID- 21721128
TI  - Mutation probability of cytochrome P450 based on a genetic algorithm and support
      vector machine.
AB  - The support vector machine (SVM), an effective statistical learning method, has
      been widely used in mutation prediction. Two factors, i.e., feature selection and
      parameter setting, have shown great influence on the efficiency and accuracy of
      SVM classification. In this study, according to the principles of a genetic
      algorithm (GA) and SVM, we developed a GA-SVM program and applied it to human
      cytochrome P450s (CYP450s), which are important monooxygenases in phase I drug
      metabolism. The program optimizes features and parameters simultaneously, and
      hence fewer features are used and the overall prediction accuracy is improved. We
      focus on the mutation of non-synonymous single nucleotide polymorphisms (nsSNPs)
      in protein sequences that appear to exhibit significant influences on drug
      metabolism. The final predictive model has a quite satisfactory performance, with
      the prediction accuracy of 61% and cross-validation accuracy of 73%. The results
      indicate that the GA-SVM program is a powerful tool in optimizing mutation
      predictive models of nsSNPs of human CYP450s.

PMID- 21721129
TI  - Design, synthesis, and biological activity of urea derivatives as anaplastic
      lymphoma kinase inhibitors.
AB  - In anaplastic large-cell lymphomas, chromosomal translocations involving the
      kinase domain of anaplastic lymphoma kinase (ALK), generally fused to the 5' part
      of the nucleophosmin gene, produce highly oncogenic ALK fusion proteins that
      deregulate cell cycle, apoptosis, and differentiation in these cells. Other
      fusion oncoproteins involving ALK, such as echinoderm microtubule-associated
      protein-like 4-ALK, were recently found in patients with non-small-cell lung,
      breast, and colorectal cancers. Recent research has focused on the development of
      inhibitors for targeted therapy of these ALK-positive tumors. Because kinase
      inhibitors that target the inactive conformation are thought to be more specific
      than ATP-targeted inhibitors, we investigated the possibility of using two known
      inhibitors, doramapimod and sorafenib, which target inactive kinases, to design
      new urea derivatives as ALK inhibitors. We generated a homology model of ALK in
      its inactive conformation complexed with doramapimod or sorafenib in its active
      site. The results elucidated why doramapimod is a weak inhibitor and why
      sorafenib does not inhibit ALK. Virtual screening of commercially available
      compounds using the homology model of ALK yielded candidate inhibitors, which
      were tested using biochemical assays. Herein we present the design, synthesis,
      biological activity, and structure-activity relationships of a novel series of
      urea compounds as potent ALK inhibitors. Some compounds showed inhibition of
      purified ALK in the high nanomolar range and selective antiproliferative activity
      on ALK-positive cells.

PMID- 21721130
TI  - The inverse type II beta-turn on D-Trp-Phe, a pharmacophoric motif for MOR
      agonists.
AB  - Herein we propose the D-Trp-Phe sequence within an inverse type II beta-turn as a
      new kind of pharmacophoric motif for MU-opioid receptor (MOR) cyclopeptide
      agonists. Initially, we observed that c[Tyr-D-Pro-D-Trp-Phe-Gly] (4), an analogue
      of endomorphin-1 (H-Tyr-Pro-Trp-Phe-NH2) lacking the crucial protonatable amino
      group of Tyr 1, is a MOR agonist with 10-8 M affinity. Molecular docking analysis
      suggested that the relevant interactions with the receptor involve D-Trp-Phe. The
      bioactive conformation of this region was investigated by selected derivatives of
      4 designed to adopt an inverse type II beta-turn. These efforts led to c[Tyr-Gly
      D-Trp-Phe-Gly] (14) and to the cyclotetrapeptide c[D-Asp-1-amide-beta-Ala-D-Trp
      Phe] (15), showing improved nanomolar affinity. Both 14 and 15 selectively bind
      MOR, as they have negligible affinity for the kappa- and delta-opioid receptors.
      Both 14 and 15 behave as partial MOR agonists in functional assays.
      Conformational and docking analyses confirm the role of the inverse beta-turn in
      binding. These results indicate that the D-Trp-Phe inverse beta-turn structure
      can be used for designing non-endomorphin-like peptidomimetic opioid agonists in
      general, characterized by an atypical mechanism of interaction between ligand and
      receptor.

PMID- 21721131
TI  - Laser-induced crystallization and crystal growth.
AB  - Recent streams of laser studies on crystallization and crystal growth are
      summarized and reviewed. Femtosecond multiphoton excitation of solutions leads to
      their ablation at the focal point, inducing local bubble formation, shockwave
      propagation, and convection flow. This phenomenon, called "laser micro tsunami"
      makes it possible to trigger crystallization of molecules and proteins from their
      supersaturated solutions. Femtosecond laser ablation of a urea crystal in
      solution triggers the additional growth of a single daughter crystal. Intense
      continuous wave (CW) near infrared laser irradiation at the air/solution
      interface of heavy-water amino acid solutions results in trapping of the clusters
      and evolves to crystallization. A single crystal is always prepared in a
      spatially and temporally controlled manner, and the crystal polymorph of glycine
      depends on laser power, polarization, and solution concentration. Upon
      irradiation at the glass/solution interface, a millimeter-sized droplet is
      formed, and a single crystal is formed by shifting the irradiation position to
      the surface. Directional and selective crystal growth is also possible with laser
      trapping. Finally, characteristics of laser-induced crystallization and crystal
      growth are summarized.

PMID- 21721132
TI  - Revisiting keteniminium salts: more than the nitrogen analogs of ketenes.
AB  - Keteniminium salts are powerful electrophilic heterocumulene reagents well-known
      for their selectivity and stereocontrol in [2+2] cycloadditions to olefins and
      carbonyl derivatives. Furthermore, they are readily accessible from stable and
      simple precursors under a variety of different conditions. Herein, we present the
      chemistry of keteniminium salts with the hindsight of time, describe preparation
      methods, recent [2+2] chemistry, mechanistic studies, and assorted applications
      that significantly extend the scope of utility of these unique electrophilic
      heterocumulenes.

PMID- 21721133
TI  - Stiff, multistimuli-responsive supramolecular hydrogels as unique molds for 2D/3D
      microarchitectures of live cells.
AB  - Supramolecular hydrogels constructed through molecular self-assembly of small
      molecules have unique stimuli-responsive properties; however, they are
      mechanically weak in general, relative to conventional polymer gels. Very
      recently, we developed a zwitterionic amino acid tethered amphiphilic molecule 1,
      which gave rise to a remarkably stiff hydrogel comparable with polymer-based
      agarose gel, retaining reversible thermal-responsive properties. In this study,
      we describe that rational accumulation of multiple and orthogonal noncovalent
      interactions in the supramolecular nanofibers of 1 played crucial roles not only
      in the mechanical reinforcement but also in the multistimuli responsiveness. That
      is, the zwitterionic amino acid moiety and the C-C double bond unit of the
      hydrogelator 1 can function as a pH-responsive unit and a light-responsive unit,
      respectively. We also demonstrated that this stiff and multistimuli-responsive
      supramolecular hydrogel 1 is applied as a unique mold for 2D and 3D-patterning of
      various substances. More significantly, we succeeded in the fabrication of a
      collagen gel for spatial patterning, culturing, and differentiation of live cells
      by using hydrogel 1 molds equipped with 2D/3D microspace channels (100-200 MUm in
      diameter).

PMID- 21721134
TI  - Synthesis and photophysical properties of dimethoxybis(3,3,3-trifluoropropen-1
      yl)benzenes: compact chromophores exhibiting violet fluorescence in the solid
      state.
AB  - Dimethoxybis(3,3,3-trifluoropropen-1-yl)benzenes were prepared through palladium
      catalyzed double cross-coupling reactions of diiododimethoxybenzenes with
      CF(3)C=CZnCl, followed by reduction of CF(3)C=C groups with LiAlH(4) or H(2) in
      the presence of the Lindlar catalyst. The edges of the absorption spectra of 1,2
      (MeO)(2)-4,5-(CF(3)CHC=CH)(2) benzenes 1 and 1,3-(MeO)(2)-4,6-(CF(3)CH=CH)(2)
      benzenes 2 in cyclohexane ranged from 348 to 360 nm, whereas the absorption
      spectra of 1,4-(MeO)(2)-2,5-[(E)-CF(3)CH=CH](2) benzene ((E)-3) ended at 406 nm.
      These findings indicate that the effective conjugation length of (E)-3 was
      significantly larger than those of 1 and 2. Consistently, 1 and 2 in cyclohexane
      exhibited fluorescence with emission maxima in the UV region, whereas (E)-3 in
      cyclohexane emitted violet light with an emission maximum at 407 nm. All the
      fluorescence spectra of 1-3 in various solvents redshifted as the solvent
      polarity increased. The photoluminescence of 1-3 in the solid states was also
      observed with emission maxima in the violet region. It is important to note that
      the quantum yields of (E)-3 in a neat thin film and in a doped polymer film were
      0.37 and 0.49, respectively. Density functional theory calculations suggested
      that the fluorine atoms contribute to a slight extension of both the HOMOs and
      the LUMOs, as well as narrowing of the HOMO-LUMO gaps when compared with the
      corresponding fluorine-free analogues. In the case of (E)-3, it is suggested that
      the HOMO-LUMO transition includes charge transfer from the ethereal oxygen atoms
      to the C(sp(2))-CF(3) moieties.

PMID- 21721135
TI  - Base-free palladium-catalyzed Sonogashira coupling using organogold complexes.

PMID- 21721136
TI  - Microwave-assisted tandem transformation on an ionic-liquid support: efficient
      synthesis of pyrrolo/pyridobenzimidazolones and isoindolinone-fused
      benzimidazoles.
AB  - A tandem transformation that involves the formation of three bonds and two
      heterocyclic rings in a one-pot fashion through amino-alkylation of an ionic
      liquid-immobilized diamine with keto acids followed by successive double
      intramolecular cyclizations to afford a tricyclic framework has been explored.
      This tandem cyclization has been utilized to develop a rapid and efficient method
      to synthesize various pyrrolo[1,2-a]benzimidazolones and pyrido[1,2
      a]benzimidazolones on an ionic-liquid support by using focused microwave
      irradiation. The application of this tandem cyclization was further extended to
      the aromatic keto acids to provide isoindolinone-fused benzimidazoles, a
      structurally heterogeneous library with skeletal diversity. The outcome of the
      cascade reaction was confirmed by the X-ray crystallographic study of the product
      directly attached to the ionic-liquid support. Use of the ionic liquid as a
      soluble support facilitates purification by simple precipitation along with
      advantages like high loading capacity, homogeneous reaction conditions, and
      monitoring of the reaction progress by regular conventional spectroscopic
      methods, whereas application of microwave irradiation greatly accelerates the
      rate of the reactions.

PMID- 21721137
TI  - Production of biofuels from cellulose and corn stover using alkylphenol solvents.

PMID- 21721138
TI  - Visuospatial information in the retinotectal system of xenopus before correct
      image formation by the developing eye.
AB  - The retinotectal pathway of Xenopus laevis is a well-established experimental
      model for studying activity-dependent processes during visual system development.
      Such processes can be guided by stimulus-evoked activity patterns, which depend
      on the refractive characteristics of the eye. Previous work has shown that many
      animals are hyperopic at early developmental stages due to immature refractive
      properties. Whether this is also the case for Xenopus laevis is unknown. Here, we
      measure the focal length of the lens and the size of the eye of embryos at
      different stages and find that Xenopus laevis exhibits a similar shift from
      hyperopia to emmetropia. At early stages, immediately after innervation of the
      tectum by the optic nerve, Xenopus embryos are hyperopic. Soon afterwards the
      focal length of the lens decreases and the eye converges to a state of
      emmetropia. Despite being hyperopic we find that some visuospatial information is
      available to the young circuit. Calculations based on the optical properties of
      the eye show that even when the animals are hyperopic the blurred retinal image
      provides a crude spatial resolution. Furthermore, using whole-cell recordings in
      the optic tectum combined with visual stimulation through the intact eye, we show
      that tectal neurons in hyperopic embryos have spatially restricted glutamatergic
      receptive fields. Our data demonstrate that Xenopus laevis eyes undergo a process
      of developmental emmetropization, and suggest that despite an initial stage of
      suboptimal image formation there is potentially enough information to guide
      activity-dependent refinements of the retinotectal pathway from the onset of
      vision.

PMID- 21721139
TI  - Epithelial membrane transporters expression in the developing to adult mouse
      vomeronasal organ and olfactory mucosa.
AB  - To contribute clarifying mechanisms operating in nose chemosensory epithelia and
      their developmental patterns, we analyzed the expression of different epithelial
      membrane transporters as well as the Clara cell secretory protein, CC26 in the
      olfactory, vomeronasal organ (VNO), and respiratory epithelia of embryonic (E13
      E19) and postnatal (P1-P60) mice by means of immunohistochemistry and reverse
      transcriptase-polymerase chain reaction. Results showed that CC26, cAMP-activated
      chloride channel (CFTR), and the water channel protein aquaporin 2, 3, 4, and 5
      (AQP2, AQP3, AQP4, and AQP5) are expressed in developing to adult chemosensory
      epithelia with differential timing; moreover, their pattern of expression is not
      identical in VNO and olfactory epithelia as well as the corresponding associated
      glands; co-localization experiments using olfactory marker protein showed that
      CFTR, CC26, and AQP4 are not expressed in olfactory neurones. CFTR is expressed
      in sustentacular cells of the VNO and olfactory epithelium as well as blood
      vessels of the underlying mucosa, and VNO (but not Bowman's) glands; a similar
      pattern (excluding blood vessels) is present for AQP2; AQP4 is found in the two
      chemosensory epithelia and in Bowman's glands. AQP3 is expressed in the olfactory
      epithelium and the associated Bowman's glands, but not in the VNO chemosensory
      epithelium and glands. AQP5 is expressed in the olfactory epithelium and both
      Bowman's and VNO glands. These results indicate that water/ions handling as well
      as antioxidant mechanisms operating at the surface and/or inside the nose
      chemosensory epithelia start developing in utero and are maintained up to sexual
      maturity.

PMID- 21721141
TI  - Benzylpiperazine: the New Zealand legal perspective.

PMID- 21721140
TI  - Informatics and standards for nanomedicine technology.
AB  - There are several issues to be addressed concerning the management and effective
      use of information (or data), generated from nanotechnology studies in biomedical
      research and medicine. These data are large in volume, diverse in content, and
      are beset with gaps and ambiguities in the description and characterization of
      nanomaterials. In this work, we have reviewed three areas of nanomedicine
      informatics: information resources; taxonomies, controlled vocabularies, and
      ontologies; and information standards. Informatics methods and standards in each
      of these areas are critical for enabling collaboration; data sharing; unambiguous
      representation and interpretation of data; semantic (meaningful) search and
      integration of data; and for ensuring data quality, reliability, and
      reproducibility. In particular, we have considered four types of information
      standards in this article, which are standard characterization protocols, common
      terminology standards, minimum information standards, and standard data
      communication (exchange) formats. Currently, because of gaps and ambiguities in
      the data, it is also difficult to apply computational methods and machine
      learning techniques to analyze, interpret, and recognize patterns in data that
      are high dimensional in nature, and also to relate variations in nanomaterial
      properties to variations in their chemical composition, synthesis,
      characterization protocols, and so on. Progress toward resolving the issues of
      information management in nanomedicine using informatics methods and standards
      discussed in this article will be essential to the rapidly growing field of
      nanomedicine informatics.

PMID- 21721142
TI  - A role for katanin in plant cell division: microtubule organization in dividing
      root cells of fra2 and lue1Arabidopsis thaliana mutants.
AB  - Severing of microtubules by katanin has proven to be crucial for cortical
      microtubule organization in elongating and differentiating plant cells. On the
      contrary, katanin is currently not considered essential during cell division in
      plants as it is in animals. However, defects in cell patterning have been
      observed in katanin mutants, implying a role for it in dividing plant cells.
      Therefore, microtubule organization was studied in detail by immunofluorescence
      in dividing root cells of fra2 and lue1 katanin mutants of Arabidopsis thaliana.
      In both, early preprophase bands consisted of poorly aligned microtubules,
      prophase spindles were multipolar, and the microtubules of expanding
      phragmoplasts were elongated, bended toward and connected to the surface of
      daughter nuclei. Accordingly, severing by katanin seems to be necessary for the
      proper organization of these microtubule arrays. In both fra2 and lue1,
      metaphase/anaphase spindles and initiating phragmoplasts exhibited typical
      organization. However, they were obliquely oriented more frequently than in the
      wild type. It is proposed that this oblique orientation may be due to prophase
      spindle multipolarity and results in a failure of the cell plate to follow the
      predetermined division plane, during cytokinesis, producing oblique cell walls in
      the roots of both mutants. It is therefore concluded that, like in animal cells,
      katanin is important for plant cell division, influencing the organization of
      several microtubule arrays. Moreover, failure in microtubule severing indirectly
      affects the orientation of the division plane.

PMID- 21721143
TI  - What could hemoptysis hide in an otherwise healthy child?
AB  - We describe a previously healthy 12-year-old boy who attended our Department
      after a sudden episode of hemoptysis and recurrent consolidation. CT-scan
      revealed a mediastinal tumor. The biopsy specimens taken from the mass showed a
      mature teratoma. Hemoptysis is an unusual presenting symptom in an otherwise
      healthy child with a well capsulated, unruptured mature mediastinal teratoma. In
      this report, hemoptysis prompted us to undertake the diagnostic work-up that
      eventually disclosed the tumor.

PMID- 21721144
TI  - Validation of a school-based written questionnaire for asthma case identification
      in Argentina.
AB  - Recognition of asthma in community-based surveys can be problematic. We sought to
      develop and validate questionnaires that could identify elementary school-aged
      children likely to have asthma or who had poorly-controlled asthma.
      Questionnaires for parents (PQ) and students (SQ) to complete were developed
      using guidance on question wording from a focus group consisting of children with
      asthma and their parents. The gold standard for this study was a pulmonologist
      determination of asthma and this was used to calculate sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) for each
      question and for combinations of questions. Questionnaires were distributed to
      830 children attending elementary schools in Trelew, Argentina and 96% were
      returned. Test-retest reliability was determined in 221 randomly selected parents
      and children and very good levels of agreement were seen for individual
      questions. Asthma was diagnosed in 92 students. Overall, the PQ was able to
      detect asthma better than the SQ. Optimal diagnostic ability came by combining
      questions from the PQ and SQ. Not surprisingly, these questionnaires had a better
      NPV than PPV and can be used to determine which children require further
      evaluation.

PMID- 21721145
TI  - Scientific publications from mainland China, Taiwan, and Hong Kong in integrative
      and complementary medicine journals: a ten-year literature survey.
AB  - Practitioners and researchers from China, the largest user of complementary and
      alternative medicine (CAM), have been publishing an increasing number of
      scientific articles in world-famous CAM journals in recent years. However, the
      status of CAM research in the three major regions of China, the Mainland, Taiwan
      and Hong Kong has, until now, not been reported. In this study, we compared
      articles from these three regions published in international CAM journals from
      2000 to 2009 using PubMed database and the Journal Citation Reports. The study
      results showed that the number of published articles from Mainland China
      increased significantly from 2000 to 2009, particularly since 2005. Meanwhile,
      the number of published articles from Taiwan also increased, whereas those from
      Hong Kong remained steady. Clinical trials and randomized controlled trials from
      Chinese authors both took a small percentage of the total. The impact factors of
      the journals in which these articles were published suggested similar academic
      levels whereas the average number of citation of articles from the Mainland was
      less than those from the other two regions. Journal of Ethnopharmacology,
      American Journal of Chinese Medicine, Journal of Alternative and Complementary
      Medicine and Evidence-based Complementary and Alternative Medicine were the most
      popular journals for Chinese authors.

PMID- 21721146
TI  - Cognition research and constitutional classification in Chinese medicine.
AB  - In the Western medicine system, scholars have explained individual differences in
      terms of behaviour and thinking, leading to the emergence of various
      classification theories on individual differences. Traditional Chinese medicine
      has long observed human constitutions. Modern Chinese medicine studies have also
      involved study of human constitutions; however, differences exist in the ways
      traditional and modern Chinese medicine explore individual constitutions. In the
      late 1970s, the constitutional theory of Chinese medicine was proposed. This
      theory takes a global and dynamic view of human differences (e.g., the shape of
      the human body, function, psychology, and other characteristics) based on
      arguments from traditional Chinese medicine. The establishment of a standard for
      classifying constitutions into nine modules was critical for clinical application
      of this theory. In this review, we describe the history and recent research
      progress of this theory, and compare it with related studies in the western
      medicine system. Several research methods, including philology, informatics,
      epidemiology, and molecular biology, in classifying constitutions used in the
      constitutional theory of Chinese medicine were discussed. In summary, this
      constitutional theory of Chinese medicine can be used in clinical practice and
      would contribute to health control of patients.

PMID- 21721147
TI  - Botanical flavonoids on coronary heart disease.
AB  - Ischemic heart disease (IHD) is one of the leading causes of death in Western
      countries. Prevention rather than treatment of heart disease can significantly
      improve patients' quality of life and reduce health care costs. Flavonoids are
      widely distributed in vegetables, fruits and herbal medicines. Regularly
      consuming botanicals, especially those containing flavonoids, has been associated
      with a reduction in cardiovascualar disease; thus, it is important to investigate
      how flavonoids improve cardiac resistance to heart disease and their related
      mechanisms of action. It has been shown that cardiomyocyte injury and death can
      result from ischemia-reperfusion, which is pathognomonic of ischemic heart
      disease. Massive reactive oxygen species (ROS) release at the onset of
      reperfusion produces cell injury and death. "Programming" the heart to either
      generate less ROS or to increase strategic ROS removal could reduce reperfusion
      response. Additionally, profuse nitric oxide (NO) release at reperfusion could be
      protective in "preconditioning" models. Botanical flavonoids induce
      preconditioning of the heart, thereby protecting against ischemia-reperfusion
      injury. In this article, we will discuss two herbs containing potent flavonoids,
      Scutellaria baicalensis and grape seed proanthocyanidin, which can potentially
      offer cardiac protection against ischemic heart disease.

PMID- 21721148
TI  - Variations of brain activities of acupuncture to TE5 of left hand in normal
      subjects.
AB  - This paper presents the evident effects of acupoint stimulation, using EEG
      (electroencephalogram) measurements. With acupuncture stimulation and the EEG
      measurement on the same meridian, EEG is able to accurately detect the effects of
      acupunctural point stimulation on brain waves. In this study, 24 subjects without
      heart or neural diseases were randomly separated into two groups of 12, named
      test and control groups. Similar procedures are performed; the subjects lay on a
      bed with eyes closed for ten minutes as the baseline. The test group received
      acupuncture at their Waiguan points (TE5) on their left hands for 20 minutes,
      while the control group did not. EEGs are recorded during pre-acupuncture,
      acupuncture stimulation and post-acupuncture stimulation periods. The EEG
      electrodes are at the T3, T4, O1 and O2 locations. Continuous wavelet
      transformation analysis is adopted; therefore, EEGs are divided into the
      following bands: delta (0.5-4HZ), theta (4-8HZ), alpha (8-13HZ) and beta (13
      30HZ). During acupuncture stimulation, the theta energy is increased and had
      statistical differences at all electrode points, T3, T4, O1 and O2. Upon removing
      the needle, the energy at the T3 and T4 points slowly declined and revealed
      obvious statistical differences. During acupuncture, only alpha energy has been
      noted to have statistical difference and it was increased at the T3 point.
      However, the energy was decreased and had no statistical difference after five
      minutes. Acupuncture is proven to be able to affect brain waves, as the
      stimulation might have changed the tissues between the cranium and scalp;
      therefore, the brain waves are detected more easily.

PMID- 21721149
TI  - Effects of acupuncture at Taixi acupoint (KI3) on kidney proteome.
AB  - This research explored and identified the protein composition of rat kidneys
      after acupuncture at the Taixi acupoint (KI3). Twelve adult male Wistar rats were
      randomly divided into a control group (n = 6) and an acupuncture group (n = 6).
      Rats in the acupuncture group received electroacupuncture on the bilateral KI3
      for seven days. The kidneys were perfused with ice-cold saline and all kidney
      proteins were isolated. After protein sample preparation, two-dimensional gel
      electrophoresis (2-DE) was performed. The interesting spots were analyzed using
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). There were nine protein spots with three-fold up-regulation in
      the kidney after the acupuncture. NAD-dependent isocitrate dehydrogenase and
      quinone reductase, the proteins involved in energy metabolism, the reduction of
      endogenous quinones, chemoprotection, and electrophilic stress, were identified.
      The data indicated that acupuncture at the KI3 of the kidney meridian of the foot
      shaoyin was able to increase NAD-dependent isocitrate dehydrogenase and quinone
      reductase expression in the kidney, and supported the relationship between the
      kidney and KI3.

PMID- 21721150
TI  - Extract of Scutellaria baicalensis Georgi root exerts protection against
      myocardial ischemia-reperfusion injury in rats.
AB  - Ischemic heart disease is a major cause of death in the world. Common therapies,
      such as primary coronary angioplasty and thrombolysis, are applied to restore
      blood supply to the heart, limit infarct size and reduce mortality. However, the
      restoration of blood supply would generate reactive oxygen species in damaged
      sites of the myocardium, intensifying the damage to the cardiac tissues. Radix
      Scutellariae baicalensis (Huangqin) is a well-known herb in traditional Chinese
      medicine with high antioxidant power. In this study, extract of the dry root of
      Scutellaria baicalensis Georgi (Sb) was confirmed to have a high content of
      flavonoids and phenolic compounds. The cardioprotective effects of the Sb
      extracts (3, 30 and 300 mg/kg) were evaluated in myocardial ischemia-reperfusion
      injuried rats. The results showed that animals that had received five-day
      pretreatment of the Sb extract (30 mg/kg) had a significant reduction in
      myocardial infarct size and a marked increase in the activity of catalase in the
      liver. The Sb extract could additionally enhance acetylcholine-induced
      vasorelaxation. It was proposed that the Sb extract exerted its cardioprotection
      by stimulating the catalase activity and improving vascular elasticity.

PMID- 21721151
TI  - Elephantopus scaber inhibits lipopolysaccharide-induced liver injury by
      suppression of signaling pathways in rats.
AB  - Elephantopus scaber (ES, Teng-Khia-U) has been traditionally used for the
      treatment of nephritis, pain, and fever; however, the direct evidence is lacking.
      We investigated the effect of ES on lipopolysaccharide (LPS) induced inflammation
      of BV-2 microglial cells and acute liver injury in Sprague-Dawley (SD) rats. Our
      results showed that ES reduced LPS-induced nitric oxide (NO), interleukin (IL)-1,
      IL-6, reactive oxygen species (ROS), and prostaglandin (PGE(2)) production in BV
      2 cells. ES significantly decreased serum aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) levels in LPS-treated rats. Furthermore, the water
      extract, but not the ethanol extract, of ES dose-dependently inhibited LPS
      induced JNK, p38 mitogen-activated protein kinases (MAPK), and slightly inhibited
      cyclooxygenase (COX-2) in BV-2 cells but decreased p38 MAPK and COX-2 expressions
      in the liver of LPS-treated rats. Taken together, these results indicate that the
      protective mechanism of ES involves an antioxidant effect and inhibition of p38
      MAP kinase and COX-2 expressions in LPS-stressed acute hepatic injury in SD rats.

PMID- 21721152
TI  - Effects of root and stem extracts of Asparagus cochinchinensis on biochemical
      indicators related to aging in the brain and liver of mice.
AB  - Asparagus cochinchinensis is a traditional Chinese medicine used for treating
      lung and spleen-related diseases. In this study, we compared the medicinal
      effects of A. cochinchinensis root and stem extracts on the activity of
      superoxide dismutase (SOD), the content of malonaldehyde (MDA) and total protein
      content in the brain, liver and plasma of mice. Polysaccharides and aqueous
      extracts of the roots significantly increased the spleen index and the SOD
      activity but reduced the MDA content and slowed down the aging process. In
      contrast, feeding with the stem extracts significantly reduced the SOD activity
      and increased the MDA accumulation in the brain and liver of mice, suggesting
      that the stem extracts may not be appropriate for treating aging-related
      diseases.

PMID- 21721153
TI  - Lung tumorigenesis suppressing effects of a commercial kava extract and its
      selected compounds in A/J mice.
AB  - Lung cancer is the most deadly malignancy in the US. Chemoprevention is
      potentially a complementary approach to smoking cessation for lung cancer
      control. Recently, we reported that a commercially available form of kava extract
      significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and
      benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice at a dose of 10 mg
      per gram diet. In the present study, we examined the dose-dependent lung tumor
      inhibitory activities of kava and investigated potential active constituent(s).
      Mice treated with carcinogen alone contained 12.1+/-5.8 lung adenomas per mouse
      22 weeks after final carcinogen administration. Mice that were fed diets
      containing kava at dosages of 1.25, 2.5, 5, and 10 mg/g of diet had 8.4+/-3.5,
      6.6+/-3.5, 4.3+/-2.4, and 3.8+/-2.3 lung adenomas per mouse, respectively. This
      corresponds to a reduction of 31%, 46%, 65% and 69% in tumor multiplicity, which
      were all statistically significant (p < 0.05). Analyses of lung adenoma tissues
      derived from kava-treated animals revealed that kava significantly inhibited
      adenoma cell proliferation while it had no detectable effect on cell death,
      indicating that kava primarily suppressed lung tumorigenesis in A/J mice via
      inhibition of cell proliferation. Flavokawains A, B, and C, three chalcone-based
      components from kava, demonstrated greatly reduced chemopreventive efficacies
      even at concentrations much higher than their natural abundance, suggesting that
      they alone were unlikely to be responsible for kava's chemopreventive activity.
      Kava at all dosages and treatment regimens did not induce detectable adverse
      effects, particularly with respect to liver. Specifically, kava treatment showed
      no effect on liver integrity indicator enzymes or liver weight, indicating that
      kava may be potentially safe for long-term chemopreventive application.

PMID- 21721154
TI  - Japanese herbal medicine TJ-48 prevents autoimmune diabetes in NOD mice.
AB  - Type 1 diabetes mellitus (T1DM) is mainly caused by CD8(+) cytotoxic T cell
      infiltration into islets. Recently, the role of regulatory T cells (Tregs) in the
      prevention of the onset of T1DM was reported. We reported that TJ-48, a common
      Japanese herbal medicine, decreased Treg population in cancer patients, thus we
      investigated whether TJ-48 had an influence on T1DM onset using NOD mice. In the
      TJ-48 group, TJ-48 (2.0g/kg/day) was administered in the drinking water for NOD
      mice from three weeks of age to 20 weeks of age. Their body weight and fast blood
      glucose (FBG) were measured every week. Histology (Hematoxylin-Eosin staining)
      was investigated every month. Lymphocyte profiles were investigated every month
      with FACS. The results were compared to the age-matched NOD mice control group.
      FBG of the control group mice showed diabetic status of 66.7% at 18 weeks of age.
      On the other hand, the TJ-48 group mice showed diabetic status of 16.7% at 18
      weeks of age (p = 1.905E-06). There were no significant differences in general
      conditions or body weight between the two groups. Lymphocyte infiltrations into
      islets were dramatically suppressed in the TJ-48 group. The effect of TJ-48 on
      decreasing Tregs was less apparent in the NOD mice model. TJ-48 inhibited
      lymphocyte infiltrations into islets, which led to preventing the onset of T1DM
      in NOD mice.

PMID- 21721155
TI  - Systems biology in a commercial quality study of the Japanese Angelica radix:
      toward an understanding of traditional medicinal plants.
AB  - The commercial quality of Japanese Angelica radices -- Angelica acutiloba
      Kitagawa (Yamato-toki) and A. acutiloba Kitagawa var. sugiyama Hikino (Hokkai
      toki) -- used in Kampo traditional herbal medicines, was studied by use of omics
      technologies. Complementary and alternative medical providers have observed in
      their clinical experience that differences in radix commercial quality reflect
      the differences in pharmacological responses; however, there has been little
      scientific examination of this phenomenon. The approach of omics, including
      metabolomics, transcriptomics, genomics, and informatics revealed a distinction
      between the radix-quality grades based on their metabolites, gene expression in
      human subjects, and plant genome sequences. Systems biology, constructing a
      network of omics data used to analyze this complex system, is expected to be a
      powerful tool for enhancing the study of radix quality and furthering a
      comprehensive understanding of all medicinal plants.

PMID- 21721156
TI  - Two-year toxicity and carcinogenicity studies of Panax ginseng in Fischer 344
      rats and B6C3F1 mice.
AB  - Ginseng is one of the most popular herbal supplements on the US market. Numerous
      reports of adverse effects from products containing ginseng have been filed with
      the US Food and Drug Administration (FDA) and the literature documents a "ginseng
      abuse syndrome" among regular users. However, the chronic toxic effects of
      ginseng are not well characterized. Because of its significant human exposure and
      the fact that little information on its toxicity is available, Panax ginseng was
      nominated by the US National Institutes of Health (NIH) to the US National
      Toxicology Program (NTP) to assess its carcinogenic potential. In this paper, we
      reported the results of NTP chronic toxicity and tumorigenicity bioassay. It
      shows that, under these experimental conditions, Panax ginseng is not toxic or
      tumorigenic.

PMID- 21721157
TI  - 1'-Acetoxychavicol acetate enhances the phase II enzyme activities via the
      increase in intranuclear Nrf2 level and cytosolic p21 level.
AB  - (1'S)-acetoxychavicol acetate ((S)-ACA) exhibits chemopreventive effects on
      chemically induced tumor formation. It has been shown that ACA inhibited the
      development of azoxymethane-induced colon carcinogenesis through its suppression
      of cell proliferation in the colonic mucosa and its induction of glutathione S
      transferase and quinone oxidoreductase 1 in vivo. In this study, we investigated
      how ACA induced these enzymes by using rat intestine epithelial cells (IEC6) in
      vitro. ACA induced glutathione S-transferase (GST) and NAD (P)H: quinone
      oxidoreductase 1 (NQO1) activities, increased intracellular glutathione (GSH)
      level, and upregulated intranuclear Nrf2 and cytosolic p21. It suggested that
      activation of phase II enzymes via Nrf2 associated with p21 is one of possible
      mechanisms of ACA to prevent advance of carcinogenesis.

PMID- 21721158
TI  - Trilinolein inhibits proliferation of human non-small cell lung carcinoma A549
      through the modulation of PI3K/Akt pathway.
AB  - Trilinolein has been identified as one of the active constituents isolated from
      Panax notoginseng used widely in traditional Chinese medicine. Protective actions
      of Panax notoginseng against cerebral ischemia, beneficial effects on the
      cardiovascular system, and hemostatic, antioxidant, hypolipidemic,
      hepatoprotective, renoprotective and estrogen-like activities have been
      illustrated. In the present study, the effects of trilinolein on the growth of
      non-small cell lung carcinoma A549 were investigated. It was found that the
      exposure of A549 cells to trilinolein resulted in the growth inhibition and the
      induction of apoptosis in a dose- and time- dependent manner. Trilinolein
      treatment induced the upregulation of pro-apoptotic Bax, downregulation of anti
      apoptotic Bcl-2 expression, which was associated with the proteolytic activation
      of caspases and the concomitant degradation of poly(ADP-ribose) polymerase (PARP)
      protein. Intracellular reactive oxygen species seem to play a role in the
      trilinolein-induced apoptosis, since ROS were produced early in the trilinolein
      treatment. Moreover, the activity of PI3K/Akt was downregulated in trilinolein
      treated cells. Our results demonstrated that the most important regulators of
      trilinolein-induced apoptosis are Bcl-2 family and caspase-3, which are
      associated with cytochrome c release and dephosphorylation on the Akt signaling
      pathway.

PMID- 21721159
TI  - Rhein lysinate induced S-phase arrest and increased the anti-tumor activity of 5
      FU in HeLa cells.
AB  - Rhein lysinate (RHL), easily dissolved in water, is one of the anthraquinones,
      and has been shown to have anti-tumor activity in different human cancer cell
      lines. In the present study, we observed that RHL could cause vacuolar
      degeneration in HeLa cells, which was not observed in human umbilical vein
      endothelial cells (HUVECs) and other cell lines (SKOV-3 and SK-BR-3). Therefore,
      the purpose of this study was to investigate the anti-tumor effect of rhein
      lysinate on human cervix cancer HeLa cells. The results indicated that RHL could
      induce HeLa cell S-phase arrest and RHL (higher than 80 MUM) also induced HeLa
      cell G2/M-phase arrest in a dose-dependent manner. Compared to the HeLa cells,
      RHL induced HUVECs G1-phase arrest at all dose levels tested in a dose-dependent
      manner. Treatment with RHL led to a significant S or G2/M-phase arrest through
      promoting the expression of p53 and p21 and the phosphorylation of p53. Moreover,
      80 MUM RHL could increase 5-FU anti-tumor activity. In conclusion, RHL could be a
      novel chemotherapeutic drug candidate for the treatment of human cervix cancer in
      the future.

PMID- 21721160
TI  - In vitro antioxidation activity and genoprotective effect of selected Chinese
      medicinal herbs.
AB  - Some traditional Chinese medicinal seeds and fruits are well known for their
      antioxidant properties. This research aims to investigate whether Fructus Lycii,
      Fructus Schisandrae Chinensis, Fructus Ligustri Lucidi and Semen Cuscutae protect
      DNA from oxidant challenge by hydrogen peroxide (H(2)O(2)). The standard comet
      assay was used to assess the genoprotective effect of these medicinal herbs.
      Blood was taken from three healthy adults, aged from 36 to 42. Lymphocytes were
      isolated and treated with different concentrations of aqueous herbal extracts,
      while controls were treated with phosphate buffered saline. The lymphocytes were
      stressed with 50 MUM H(2)O(2). Treated cells were embedded in agarose and layered
      on slides. These sandwiched lymphocytes were lysed and afterwards subjected to an
      electric field in an alkaline environment. Damaged DNA was pulled out from the
      nucleus towards the positive electrode as a comet tail; its density was related
      to the degree of DNA damage. Finally, the slides were stained with fluorescence
      dye and tails were visually scored for 100 cells. The experiment was repeated
      three times and DNA damage in treated cells was compared to the controls. There
      was no statistical difference in DNA damage among the herb treated cells and
      untreated cells in the comet assay. Our data demonstrated that the selected
      medicinal herbs did not show in vitro DNA protection in the comet assay against
      oxidant challenge.

PMID- 21721161
TI  - The value of postoperative/preadjuvant chemotherapy computed tomography in the
      management of patients with ovarian cancer.
AB  - OBJECTIVE: The objectives of the study were to compare the operative assessment
      of residual disease with the postoperative computed tomography (CT) findings in
      patients with ovarian cancer who underwent primary surgical cytoreduction or
      interval debulking surgery to residual disease 1 cm or less and to assess the
      effect of potential prognostic factors on patient survival. METHODS: Patients
      scheduled for surgery and with an available postoperative CT were eligible for
      the study. Images were retrospectively analyzed in consensus by 2 radiologists.A
      5-point qualitative scoring system was used to evaluate the CT findings (1 =
      tumor definitely absent, 2 = tumor probably absent, 3 = tumor possibly present, 4
      = tumor probably present, 5 = tumor definitely present). RESULTS: Between
      September 2005 and December 2008, 206 consecutive patients were enrolled; 51 were
      eligible. In 30 cases (59%), the postoperative CT findings correlated with the
      surgeon's assessment of residual disease. For the univariate analyses, the only
      significant prognostic factors associated with overall survival were no residual
      disease versus residual disease of less than 1 cm as assessed by the surgeon
      (hazard ratio [HR], 3.06; 95%confidence interval [CI], 1.29--7.27; P = 0.011) and
      no residual disease versus residual disease greater than 1 cm on CT (HR, 2.57;
      95% CI, 1.02--6.48; P = 0.045). The interaction of surgical residual disease and
      stage 3 was significant (HR, 3.40; 95% CI, 1.42--8.16;P = 0.006) in the
      multivariate Cox model. CONCLUSIONS: There was only 59% correlation between the
      surgical assessment and post operative CT findings of residual disease in
      patients reported to have undergone optimal surgery. Stage and residual disease
      as assessed by the surgeon were significant prognostic factors for overall
      survival. The value for postoperative CT may lie in those cases with small-volume
      residual disease (visible but reported as G1 cm) at surgery.

PMID- 21721162
TI  - [Toward a transformation of the team concept?].

PMID- 21721163
TI  - [Committee for Permanent Development of the Wellbeing of Caregivers].

PMID- 21721164
TI  - [A noteworthy special case].

PMID- 21721165
TI  - [Cattle-plague is no longer on Earth].

PMID- 21721166
TI  - [New data on risks and benefits: beta blockers despite asthma? (interview by Dr.
      Beate Schumacher)].

PMID- 21721167
TI  - [With blood samples caught in the business tax trap: can I still get out?].

PMID- 21721168
TI  - [Management of nodular goiter: a solution for thyroid nodules].

PMID- 21721169
TI  - How to prepare lung specimens for  sectioning in cryostat.

PMID- 21721171
TI  - Multivitamin use and the risk of myocardial infarction.

PMID- 21721170
TI  - Insights from model organisms on the functions of the tumor suppressor protein
      LKB1: zebrafish chips in.
AB  - The tumor suppressor LKB1 has emerged as a critical regulator of cell polarity
      and energy-metabolism. Studies in diverse model organisms continue to unravel the
      pathways downstream of LKB1; the emerging picture is that the outcomes of LKB1
      signaling are mediated by a plethora of tissue-specific and context-dependent
      effectors.

PMID- 21721172
TI  - WHI dietary modification trial - disappointing results?

PMID- 21721173
TI  - Postmenopausal depression and dementia: are the 2D's connected?

PMID- 21721174
TI  - Effect of hormone therapy on lean body mass, falls and fractures.

PMID- 21721175
TI  - Endogenous androgens and effects on body fat and insulin resistance Casson.

PMID- 21721176
TI  - Paths to the making of an academic clinical investigator--part 1.

PMID- 21721177
TI  - Abstracts of the International Surgical Congress of the Association of Surgeons
      of Great Britain and Ireland. May 11-13, 2011. Bournemouth, United Kingdom.

PMID- 21721178
TI  - [Abstracts of the 60th Annual North German Orthopedic and Injury Surgery Society.
      June 16-18, 2011. Hamburg, Germany].

PMID- 21721179
TI  - Abstracts of the Association of Coloproctology of Great Britain and Ireland
      Annual Meeting. June 20-23, 2011. Birmingham, United Kingdom.

PMID- 21721180
TI  - Abstracts of the 71st American Diabetes Association Scientific Sessions. June 24
      28, 2011. San Diego, California, USA.

PMID- 21721181
TI  - Gearing up to get blood pressure down: Hypertension Excellence Centres.
AB  - Despite efforts to prevent and manage hypertension using drugs andguidelines,
      patients in Europe appear to have higher blood pressurelevels and worse
      hypertension control than patients in the USA.

PMID- 21721182
TI  - Endothelial biology in humans: from acetylcholine testing in coronary arteries to
      personalized management of coronary heart disease.
AB  - The role of acetylcholine in determining the tone of blood vessels.

PMID- 21721183
TI  - Social animal: how the new sciences of human nature can help make sense of a
      life.

PMID- 21721184
TI  - We can't feel their pain, but we can understand their fears.

PMID- 21721185
TI  - Obesity in South Dakota: an expanding epidemic.

PMID- 21721186
TI  - The obesity epidemic in South Dakota: how big is the problem?
AB  - Obesity is an increasing problem both in the United States and South Dakota.
      Currently, 30.3 percent of South Dakota adults self-report being obese, which is
      higher than the national prevalence and also increasing at a faster rate than
      other states. The obesity rate for South Dakota 2- to 5-year-olds from limited
      income households is 16.4 percent and above the national prevalence. Obesity
      prevalence among students Kindergarten through grade 12 was 16.0 percent for the
      2009-2010 school year, not higher than national data.

PMID- 21721187
TI  - The effect of obesity on orthopaedic conditions.
AB  - Obesity is a worldwide health problem leading to a range of health consequences.
      This review summarizes the known effects of obesity on the musculoskeletal
      system. Specifically, the effects of obesity on the shoulders, spine, knees, feet
      and other areas related to sports medicine are examined.

PMID- 21721188
TI  - Obesity in pregnancy.
AB  - More than one-third of U.S. women are obese, and the prevalence of obesity in
      childhood has increased. Excessive gestational weight gain and obesity are
      independent risk factors for maternal and fetal complications of pregnancy and
      may very well be implicated in the epidemic of childhood obesity currently seen
      in the U.S. There are many pregnancy related complications associated with
      obesity, including miscarriage, infertility and congenital anomalies as well as a
      variety of late-pregnancy related complications. Additionally, obesity can
      predispose to the development of fetal macrosomia which can lead to childhood
      obesity. This article reviews the effects of obesity on pregnancy and potential
      methods of prevention.

PMID- 21721189
TI  - Metabolic and bariatric surgery for obesity: a review.
AB  - The obesity epidemic in the United States is plaguing both the adult and
      pediatric population. As BMI increases, life expectancy drops. Metabolic and
      bariatric surgery can be an effective option for morbidly obese patients to
      enable substantial, sustained weight loss and result in improvement or resolution
      of comorbidities. The National Institutes of Health's criteria for bariatric
      surgery includes patients with a BMI of 35 and associated comorbidities, or a BMI
      of 40 and have failed conservative management. Currently, the common surgeries
      done in the United States are the laparoscopic Roux-en-Y gastric bypass, the
      laparoscopic adjustable gastric band, the biliopancreatic diversion with duodenal
      switch and the sleeve gastrectomy. Complications of the surgery are related
      either to the stapling, origin of the surgery or the implantable device. Optimal
      outcomes for patients are achieved with a Center of Excellence designated surgeon
      and designated facility, demonstrated operative skill, quality outcomes,
      multidisciplinary support, minimal complications and number of procedures
      completed. Insurance companies have seen the benefit of covering metabolic and
      bariatric surgery with comorbidity reduction and reduced health care costs. A
      multidisciplinary approach to postoperative care includes a dietician, exercise
      physiologist, psychologist and bariatric nurse coordinator as part of the
      bariatric surgery team. Metabolic and bariatric surgery pared with healthy food
      choices and regular exercise is imperative to achieve the desired goal of long
      term weight loss and comorbidity resolution.

PMID- 21721190
TI  - Obesity and type 2 diabetes mellitus in South Dakota: focused insight into
      prevalence, physiology and treatment.
AB  - Type 2 diabetes mellitus is one of the significant comorbidities of obesity. This
      review addresses the prevalence of obesity and diabetes mellitus nationally and
      in South Dakota. It elaborates on some of the mechanisms of association of
      obesity with diabetes mellitus, including effects related to adipokines,
      lipotoxicity, vitamin D deficiency and apolipoprotein C1. This review addresses
      the prevention and treatment of diabetes mellitus in the obese population through
      life style changes, medications and/or surgery. Future directions in the
      management of diabetes are explored in the obese population.

PMID- 21721191
TI  - Aggressive prostate cancer: high blood levels of omega-3s doubled the risk, but
      high levels of trans-fatty acids cut risk in half.

PMID- 21721192
TI  - Frequency and distribution of lymph node metastases in epithelial ovarian cancer.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate the incidence and
      distribution of nodal metastases in relation to the serous versus nonserous
      histological subtypes of epithelial ovarian cancer. METHODS: Patients were
      treated primarily with upfront surgery, including pelvic and paraaortic
      systematic lymphadenectomy, up to the level of the left renal vein, before any
      kind of chemotherapy administration. Patients were classified according the tumor
      histology into 2 groups: serous (including the cases of mixed histology with a
      serous component) and nonserous group. RESULTS: A total of 173 patients fulfilled
      the inclusion criteria; 76 and 97 patients had serous and nonserous ovarian
      carcinoma, respectively. Positive lymph nodes were found in 59.3% (45/76) and
      14.4% (14/97) of patients in the serous and nonserous histology
      groups,respectively. There was no difference in positive node distribution in 3
      regions (pelvic and para-aortic regions, below and above the inferior mesenteric
      artery) between these 2 groups. Early spread including 1 or 2 positive lymph
      nodes was predominantly found in the para-aortic region in both groups, serous
      and nonserous, whereas distribution of positive nodes in patients with 3 or more
      lymph nodes shows equal presence in pelvic and para-aortic regions. CONCLUSIONS:
      Serous ovarian carcinomas are much more prone to metastasize to lymph nodes than
      nonserous histological types. However, the pattern of lymph node distribution did
      not differ between these 2 groups and was similar in the pelvic and para-aortic
      regions.

PMID- 21721193
TI  - Parametrial involvement in FIGO stage IB1 cervical carcinoma diagnostic impact of
      tumor diameter in preoperative magnetic resonance imaging.
AB  - BACKGROUND: In the surgical treatment for early-stage cervical carcinoma, it is
      important to identify preoperatively a low-risk group of patients as candidates
      for less radical surgery to avoid the morbidity associated with radical
      hysterectomy. The aim of this study was to evaluate the correlation between tumor
      diameter measured preoperatively using magnetic resonance imaging (MRI) and
      pathological prognostic factors in International Federation of Gynecology and
      Obstetrics (FIGO) stage IB1 cervical carcinoma. METHODS: A total of 125 patients
      with FIGO stage IB1 cervical cancer were included in this study. Clinical
      records, pathology reports, and MRI findings were retrospectively reviewed.
      RESULTS: Histological diagnosis was squamous cell carcinoma in 57 patients and
      non squamous cell carcinoma in 68 patients. All patients underwent preoperative
      evaluation by MRI within a median period of 13.5 days before surgery. The tumor
      diameter measured by MRI ranged from zero (no tumor detected) to 42 mm, with a
      median of 23 mm.Pathological prognostic factors included parametrial involvement,
      lymph node metastasis,deep stromal invasion, and lymphovascular space invasion.
      All these factors were found less frequently in patients with a smaller tumor
      diameter. Most notably, parametrial involvement was seen in none of the patients
      with tumors 20 mm or less and was detected only in patients with tumors greater
      than 20 mm (P = 0.01). CONCLUSIONS: In the FIGO stage IB1 cervical carcinoma, the
      tumor diameter measured preoperatively by MRI correlates well with other
      pathological prognostic factors, especially with parametrial involvement. This
      finding suggests that the tumor diameter measured in preoperative MRI may serve
      as a strong predictor of parametrial involvement in FIGO stage IB1 cervical
      carcinoma, which can be used to select a candidate population for less radical
      surgery without the need for a cone biopsy before hysterectomy.

PMID- 21721194
TI  - Cardiac centre of excellence: Duke Heart Center.
AB  - Famous for the development of electrophysiology, the Duke Heart Center has grown
      from a regional centre to one of international importance

PMID- 21721195
TI  - Could cut-price cardiovascular procedures in India help Europe's hard-pressed
      health-care systems?
AB  - Until recently, travelling to India for a cardiovascular procedure was unheard
      of, but huge improvements in the quality of medical care available in the
      subcontinent, and its relative cheapness, have fostered the growth of 'medical
      tourism' and could impact on health care in Europe, reports Barry Shurlock, PhD.

PMID- 21721196
TI  - Multidetector CT angiography in acute gastrointestinal bleeding: why, when, and
      how.
AB  - Acute gastrointestinal (GI) bleeding remains an important cause of emergency
      hospital admissions, with substantial related morbidity and mortality. Bleeding
      may relate to the upper or lower GI tract, with the dividing anatomic landmark
      between these two regions being the ligament of Treitz. The widespread
      availability of endoscopic equipment has had an important effect on the rapid
      identification and treatment of the bleeding source. However, the choice of upper
      or lower GI endoscopy is largely dictated by the clinical presentation, which in
      many cases proves misleading. Furthermore, there remains a large group of
      patients with negative endoscopic results or failed endoscopy, in whom additional
      techniques are required to identify the source of GI bleeding. Multidetector
      computed tomography (CT) with its speed, resolution, multiplanar techniques, and
      angiographic capabilities allows excellent visualization of both the small and
      large bowel. Multiphasic multidetector CT allows direct demonstration of bleeding
      into the bowel and is helpful in the acute setting for visualization of the
      bleeding source and its characterization. Thus, multidetector CT angiography
      provides a time-efficient method for directing and planning therapy for patients
      with acute GI bleeding. The additional information provided by multidetector CT
      angiography before attempts at therapeutic angiographic procedures leads to
      faster selective catheterization of bleeding vessels, thereby facilitating
      embolization. Supplemental material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.313105206/-/DC1.

PMID- 21721197
TI  - Diffusion-weighted MR imaging of solid and cystic lesions of the pancreas.
AB  - Diffusion-weighted magnetic resonance (MR) imaging is increasingly used in the
      detection and characterization of pancreatic lesions. Diffusion-weighted imaging
      may provide additional information to radiologists evaluating patients who have
      cystic or solid neoplasms of the pancreas. Because of greater freedom of motion
      of water molecules in fluid-rich environments, simple cysts in the pancreas have
      higher signal intensity on diffusion-weighted images with a b value of 0 sec/mm2
      and lower signal intensity on high-b-value images. High apparent diffusion
      coefficient (ADC) values can be obtained on ADC maps because of the T2 "shine
      through" effect. In contrast, solid neoplasms of the pancreas show increased
      signal intensity relative to the pancreas on diffusion-weighted images with a b
      value of 0 sec/mm2 and relatively high signal intensity on high-b-value images.
      Diffusion-weighted imaging can help detect solid pancreatic neoplasms with
      extremely dense cellularity or extracellular fibrosis by demonstrating
      significantly low ADC values, and these neoplasms may be better detected on
      diffusion-weighted MR images because of better contrast, although the resolution
      is generally worse. However, diffusion-weighted imaging may not be capable of
      helping definitively characterize solid lesions as inflammatory or neoplastic
      because of an overlap in ADC values between the two types. For example, it is
      difficult to distinguish poorly differentiated pancreatic adenocarcinoma from
      mass-forming pancreatitis at diffusion-weighted imaging because of similarly low
      ADC values attributed to dense fibrosis.

PMID- 21721198
TI  - Invited commentary.

PMID- 21721199
TI  - Dual roles and conflict--nurses as mothers of critically ill neonates.

PMID- 21721200
TI  - [Diversity and individualization of cancer treatment].

PMID- 21721201
TI  - [Melanoma: a new therapeutic era].
AB  - Melanoma is the cancer with the fastest incidence increase in Switzerland. 30% of
      the cases arise before the age of 50 years. Once metastatic, the median survival
      under current systemic therapies is about 8 months, with less than 5% of patients
      alive at 5 years. Many efforts in the understanding of cellular biology,
      intracellular signaling pathways, as well as the role of cellular immunity have
      been made in the recent years. This has resulted in the development of novel and
      very promising therapies. In this review, we will cover the results obtained with
      targeted therapies such as "tyrosin kinase inhibitors" (TKI), as well as those
      obtained with a monoclonal antibody directed against the CTLA-4 receptor of
      lymphocytes.

PMID- 21721202
TI  - [Targeted therapies in digestive oncology].
AB  - Targeted therapies are relatively new molecules available for the oncologist.
      These drugs target a specific step of the cellular development and interfere with
      the intracellular signalization pathways. Amongst all others, EGF- and VEGF
      pathways are currently targeted by these selective therapies. Modulating EGF and
      VEGF significantly improves overall survival and progression-free survival for
      many advanced or metastatic tumors as colorectal cancer, gastric cancer,
      gastrointestinal stromal tumors or hepatocellular carcinoma. Targeted therapies
      have a specific action site, a simple administration mode and are relatively well
      tolerated. In the future these molecules will probably be used "a la carte" for
      tumors that appear to be refractory to other drugs.

PMID- 21721203
TI  - [PARP inhibitors: new therapeutic agents in breast and ovarian cancer].
AB  - PARP inhibitors are novel drugs under development in oncology, particularly
      against breast and ovarian cancer. They act on the DNA repair mechanisms in
      synergy with the loss of BRCA function of the tumor cells, thereby inducing a
      genetic instability that leads to cell death. The clinical benefit of PARP
      inhibitors has been demonstrated for breast and ovarian cancer in BRCA germline
      mutation carriers. Their use in sporadic triple negative breast cancers, that
      share similarities with BRCA1 mutated tumors, is currently investigated with
      encouraging preliminary results.

PMID- 21721204
TI  - [Jevtana: clinically significant improvement in survival of patients previously
      treated with docetaxel].

PMID- 21721205
TI  - [Management of anal canal carcinoma].
AB  - Although anal canal squamous cell carcinoma is rare, the general practitioner
      should consider this diagnosis in a patient with persistent lower abdominal
      symptoms. While classically observed in older women, an increased incidence is
      also seen in HIV-positive patients or patients with a history of human
      papillomavirus infection. Initial diagnosis and local work-up require assessment
      by a proctologist. Standard curative treatment combines radiotherapy with 5-FU-
      and MMC-based chemotherapy. Salvage surgery should be discussed in case of local
      relapse. The general practitioner, the proctologist and the radiation oncologist,
      all participate in post-treatment surveillance.

PMID- 21721206
TI  - [Cancer and aging: an epidemiological fact].
AB  - Over the last fifty years we have witnessed the ageing of the population, leading
      to changes in patterns of morbidity and causes of mortality, with cancer being
      strongly represented. In the elderly population, oncological disease should be
      assessed differently than in younger patients. Indeed, the characteristics and
      the evolution of cancer, as well as patient care, vary with ageing. It is
      therefore essential to establish specific screening strategies and therapeutic
      support, by integrating this population in clinical trials, and taking into
      account the global needs of the elderly patient.

PMID- 21721207
TI  - [Therapeutic adherence to oral cancer therapy and interdisciplinary management].
AB  - Medication adherence is a well-known risk factor in internal medicine. However in
      oncology this dimension is emerging due to the increasing number of oral
      formulations. First results in the oral oncology literature suggest that
      patients' ability to cope with medical prescription decreases with time. This
      might preclude patients from reaching clinical outcomes. Factors impacting on
      medication adherence to oral oncology treatments have not been yet extensively
      described neither strategies to address them and support patient's needs.
      Oncologists and pharmacists in our University outpatient settings performed a
      pilot study which aimed at measuring and facilitating adherence to oral oncology
      treatments and at understanding determinants of patient's adherence. The ultimate
      purpose of such a patient-centered and interdisciplinary collaboration would be
      to promote patient self-management and complement the standard medical follow-up.

PMID- 21721208
TI  - [Heartburn: you can choose to support in the short term].

PMID- 21721209
TI  - [A bittersweet spring. Office visits].

PMID- 21721210
TI  - [Gums and aorta; tobacco and the brain].

PMID- 21721211
TI  - [Women's biological clocks beat faster].

PMID- 21721212
TI  - [Away from cliche thinking].

PMID- 21721213
TI  - ["Mature nursing personnel are a gift to the team"].

PMID- 21721214
TI  - [Assessing and understanding].

PMID- 21721215
TI  - [Transparent, verifiable and practice oriented].

PMID- 21721216
TI  - [Research knowledge available in routine practice].

PMID- 21721217
TI  - [From the hectic nursing routine into the quiet archive (interview by Margit
      Bachl)].

PMID- 21721218
TI  - [Getting a grip on tumor pain].

PMID- 21721219
TI  - [Becoming a nurse today].

PMID- 21721220
TI  - [The future is intergenerational].

PMID- 21721221
TI  - [More security and comfort for patients].

PMID- 21721222
TI  - [What changes in perspective in view?].

PMID- 21721223
TI  - [Discover cycloliterature].

PMID- 21721224
TI  - [A respectful attitude behind bars].

PMID- 21721225
TI  - [An appeal that was successful].

PMID- 21721226
TI  - [Those over 50: a gift not to be underestimated].

PMID- 21721227
TI  - [Phylogenetic analysis of rust fungi (Uredinales) from the Colombian Andean
      region using 28S ribosomal DNA sequences].
AB  - Rust fungi (Uredinales, Basidiomycetes) are one of the most diverse and
      economically important plant-obligated parasites. Taxonomy of this group has been
      under revision during the last years using molecular techniques to define
      phylogenetic relationships. In this study we evaluated the phylogenetic
      affinities of a group of 40 rust fungi obtained from different plants in the
      Colombian Andean region using sequence analysis of the 28S ribosomal DNA,
      specifically D1/D2 domains. Comparisons were undertaken with sequences of rust
      fungi from around the world deposited in the GenBank database. An alignment of
      sequences was used to build a phylogenetic tree through Maximum parsimony
      analysis. Our results support the taxonomical validity of families Pucciniaceae,
      Phakopsoraceae, Phragmidiaceae, Pileolariaceae, Mikronegeriaceae, Coleosporiaceae
      and Cronartiaceae, while Pucciniosiraceae represents redundant taxa with
      Pucciniaceae. The analyses indicated that Uropyxidaceae, Raveneliaceae,
      Chaconiaceae and Pucciniastraceae correspond to polyphyletic families.
      Melampsoraceae appear to be a basal taxon to the Uredinales. Information obtained
      in this study will be useful to incorporate a higher number of sequences from
      tropical rust fungi within global efforts to redefine the taxonomy of order
      Uredinales. Additionally, we propose to give priority to future phylogenetic
      studies of taxa: Gerwasia, Hemileia, Phragmidium, Prospodium, Puccinia and
      Uromyces, genera that include a high number of rust fungi from the tropics.

PMID- 21721228
TI  - [Leaf epidermis ultrastructure of Zeugites (Poaceae: Panicoideae)].
AB  - The genus Zeugites comprises eleven species of neotropical grasses and it is
      principally distributed in Mexico, with some species extending to the Caribbean
      region, Central and South America. In this work, leaf epidermis ultrastructure of
      11 species is described by the use of scanning electron microscopy. At least
      three specimens per species, that included herbarium and collected specimens,
      were used. An identification key and specific descriptions are included, in which
      the distinctive epidermal features are highlighted. The taxonomic valuable
      characters found were the following: presence or absence of prickles and
      macrohairs, intercostals short cells form and silica body form. Based on leaf
      epidermis characteristics, Zeugites species can be arranged into three groups:
      (1) species that lack prickles (Z. americana, Z. mexicana, Z. pringlei, Z.
      munroana and Z. sagittata); and lack macro hairs, with the exception of Z.
      pringlei; (2) species that have prickles (Z. latifolia and Z. smilacifolia); (3)
      species that have both, prickles and macrohairs (Z. capillaris, Z. hackelii, Z.
      pittieri and Z. sylvatica). The morphological features of leaf epidermis, support
      the relationship between the tribes Centotheceae and Paniceae.

PMID- 21721229
TI  - [Chemical composition of essential oils from leaves of Helicteres guazumifolia
      (Sterculiaceae), Piper tuberculatum (Piperaceae), Scoparia dulcis (Arecaceae) and
      Solanum subinerme (Solanaceae) from Sucre, Venezuela].
AB  - Essential oils, biosynthesized and accumulated in aromatic plants, have a wide
      range of applications in the pharmaceutical health, cosmetics, food and
      agricultural industry. This study aimed to analyze the secondary metabolites in
      some plant species in order to contribute to their chemotaxonomy. Leaves from
      Helicteres guazumifolia, Piper tuberculatum, Scoparia dulcis and Solanum
      subinerme were collected and their essential oils were obtained by means of hydro
      distillation. The oil fraction was analyzed and identified by GC/MS. The
      extraction yields were of 0.004, 0.032, 0.016 and 0.005%, and the oil
      constituents of 88.00, 89.80, 87.50 and 89.47%, respectively. The principal oils
      found were: non-terpenoids volatile secondary metabolites (30.28%) in H.
      guazumifolia; sesquiterpenoids (20.82 and 26.09%) and oxigen derivated (52.19 and
      25.18%) in P. tuberculatum and S. dulcis; and oxigen diterpenoids (39.67%) in S.
      subinerme. The diisobuthylphtalate (13.11%) in H. guazumifolia, (-)-spathulenol
      (11.37%) in P. tuberculatum and trans-phytol (8.29 and 36.00%) in S. dulcis and
      S. subinerme, were the principal constituents in their respective essential oils.
      The diisooctylphtalate were the essential oil common to all species, but the
      volatile compounds such as trans-pinane, L-linalool, beta-ionone, isophytol,
      neophytadiene, trans-phytol, dibutylphtalate and methyl hexadecanoate, were only
      detected in three of these essences. This suggests that these plants may require
      similar secondary metabolites for their ecological interactions, possibly due to
      common environmental factors.

PMID- 21721230
TI  - [Biology and fishery of the lobster Panulirus gracilis in Playa Lagarto,
      Guanacaste, Costa Rica].
AB  - Panulirus gracilis is a high valuable lobster species with considerable captures
      along the tropical Pacific coast. In this study, I present some biological and
      fishery parameters described after a sample of 843 lobsters, landed in Playa
      Lagarto from November 2007 to October 2008. From landing records, a total of
      74.9% of lobsters were below the minimum legal catch size (80 mm CL). Carapace
      lengths were in the range of 42.8 and 143.6 mm for males and 115 and 35.8 mm for
      females. The size structure showed a wide overlapping of population segments, and
      a trend to increase with depth, where lung diving and "hooka" diving operations
      take place. Sex ratio was 1.36 M:H. The relationship between weight and LC
      revealed that females are heavier than males of the same size, and this
      difference was significant (p < 0.05). The von Bertalanffy growth parameters for
      males and females respectively (K = 0.45-0.38, LC(infinity) = 166.9-121.7) showed
      accelerated growth compared to other species. Males observed a higher growth rate
      than females. Furthermore, natural mortality (M), total mortality (Z) and fishing
      mortality (F) was higher in males (0.49-2.34-1.92) than in females (0.47-1.82
      1.42). Recruitment was continuous for both sexes during the year, with an
      elevated intensity of 18.5% in July. Under the current fishing regime the
      population could be at risk of collapse, as indicated by the high exploitation
      rate (E) 0.80

PMID- 21721231
TI  - [Aquatic insects and water quality in Penas Blancas watershed and reservoir].
AB  - The aquatic insects have been used to evaluate water quality of aquatic
      environments. The population of aquatic insects and the water quality of the area
      were characterized according to the natural and human alterations present in the
      study site. During the monthly-survey, pH, DO, temperature, water level, DBO, PO4
      and NO3 were measured. Biological indexes (abundance, species richness and the
      BMWP-CR) were used to evaluate the water quality. No relation between
      environmental and aquatic insects was detected. Temporal and spatial differences
      attributed to the flow events (temporal) and the presence of Penas Blancas
      reservoir (spatial). In the future, the investigations in Penas Blancas watershed
      need to be focused on determining the real influence of the flows, sediment
      release and the possible water quality degradation because of agriculture
      activities.

PMID- 21721232
TI  - [Fishery of oceanic and coastal sharks in Colima, Jalisco and Michoacan].
AB  - Shark fishery is one of the most important activities in the Mexican Pacific
      coast, nevertheless, there is few data available about the specific captures done
      by the fleet along the coast. This study describes fishery biology aspects of the
      shark species catched by the semi-industrial long-line fleet of Manzanillo.
      Monthly samplings were made on board of these vessels during an annual period
      from April 2006 to April 2007. Captured species composition (n = 1 962 organisms)
      was represented by nine species. The one that sustains this fishery was
      Carcharhinus falciformis (88.12%), followed by Prionace glauca (8.21%). Low
      frequency species were represented by Sphyrna zygaena (1.78%), Alopias pelagicus
      (0.82%), Carcharhinus longimanus (0.45%). Furthermore, rare species were Alopias
      superciliosus (0.35%), Carcharhinus leucas (0.1%), Carcharhinus limbatus (0.1%)
      and Isurus oxyrinchus (0.05%). Fishery activity affected principally (60-92.70%)
      young males of C. falciformis, S. zygaena, C. longimanus and I. oxyrinchus; adult
      males (56-75%) of A. pelagicus, A. superciliosus, and C. limbatus; for P. glauca
      there were primarily female adults. For all the species found, females showed the
      bigger sizes when compared to males (with the exception of S. zygaena, that
      showed sexual dimorphism). Considering the lineal regressions made between
      precaudal length and total length, and, fork length and total length for C.
      falciformis, P. glauca, S. zygaena and A. pelagicus, the determination
      coefficients (r2) showed that both lengths can be useful to obtain the total
      length of fish with some damage or absence of its caudal fin. The estimated
      fecundity for C. falciformis was of 3-7 offspring/female of 30-45 cm LT (average
      of 40.57 +/- 2.03 cm LT); and for P. glauca 5-52 offspring/female of 5-18.6 cm LT
      (average of 11.61 +/- 0.21 cm LT). In the case of C. longimanus only one female
      was captured with a total of eight embryos, with an average of 45 cm LT each; for
      this reason we assumed that the fishery areas do not coincide with the nursery
      oness for this species. According to the information obtained, we concluded that
      C. falciformis has a concurrent cycle and P. glauca a consecutive biannual one.

PMID- 21721233
TI  - [Karyotypic characterization in mitosis and meiosis of the common snook
      Centropomus undecimalls (Pisces: Centropomidae)].
AB  - The common snook Centropomus undecimalis inhabits marine, brackish and freshwater
      habitats in the Western Central Atlantic Ocean, including the Gulf of Mexico.
      Common snook is an economically important fish in many localities, nevertheless
      the number of studies on its biology and genetics are still few. The present
      study attempts to establish the cytogenetic profiles of the specimens collected
      in Paraiso Municipality Tabasco, Mexico. Tissue of five females and eight male
      organisms were processed by conventional cytological techniques to obtain
      chromosome slides of high quality in order to assemble the karyotype. The results
      from the kidney tissue analysis showed that 85.1% of 288 mitosis had a 2n = 48
      chromosomes, and 52.8% of 104 meiosis exhibited the haploid number 1n = 24. The
      diploid karyotype showed 48 monoarmed chromosomes of the telocentric (T) type.
      There was no chromosome heteromorphism between females and males. The diploid
      karyotype was very similar to that observed in the majority of marine fishes.

PMID- 21721234
TI  - [Ichthyofauna from wetlands of San Pedro, Balancan, Tabasco, Mexico].
AB  - San Pedro River's wetlands sustain trophic nets in the fluvial system, due to the
      high habitat availability, and space and temporal variations. In order to
      describe the relationship between environmental parameters and ichthyofauna, this
      study evaluated fish assemblages composition, distribution, abundance, density,
      biomass, richness species, diversity and equitability in the wetlands. Sampling
      considered three different sites and climatic seasons (dry, rainy and cold
      fronts). The physical and chemical parameters considered were dissolved oxygen,
      temperature, pH, water transparency and the depth. Fishes were caught with a
      shrimp net, after six minutes towings and were identified afterwards. A total of
      1 049 organisms of 25 fish species were caught, two of which were exotic species:
      Oreochromis niloticus and Parachromis managuense. A total of 23 species were
      found at site I (with the highest density 0.23 ind./m2), 17 at site II (0.23
      ind./m2) and 14 at site III (0.12 ind./m2). The dry season had the highest
      species number with 21 species, followed by the rainy season with 17 species, and
      the cold season with five species. Similarly, the highest biomass (8.30 g/m2) was
      found in dry season, followed by the rainy (2.16 g/m2) and the cold seasons (0.03
      g/m2). Considering seasons, highest density was found during the dry (0.436
      ind./m2), followed by the rainy (0.213 ind./m2) and the cold (0.023 ind./m2)
      seasons. The dominant density species during the study period, according to the
      quadrants graphic of Olmstead-Tukey were: Petenia splendida, Vieja heterospila,
      Vieja synspila, Dorosoma petenense and Astyanax aeneus. There were significant
      differences in the species richness among sites. Temperature, depth and
      transparency showed differences among the seasons. The canonical correspondence
      analysis indicated that fish distribution was governed by environmental
      parameters during all seasons. In terms of fish abundance and composition,
      environmental parameters play an important role showing spatial and temporal
      differences in the ecosystem, this could be explained with the fact that most of
      young fishes have a movement behavior to the wetlands, searching refuge and feed
      during the dry season. Considering the diversity indexes variation, it may be
      concluded that San Pedro River's wetlands correspond to a system where the
      ichthyofauna composition fluctuates spatial and seasonally.

PMID- 21721235
TI  - [Morphology of the species Hyphessobrycon, heterorhabdus group (Characiformes:
      Characidae) in Colombia].
AB  - Hyphessobrycon is the most numerous and morphologically complex genus of
      Characidae, and includes 18 species reported for Colombia, from which thirteen
      belong to the heterorhabdus-group different methods have been proposed for
      species identification within this genus. This study used these species to
      undertake a morphogeometric analysis by the Box Truss and Thin Plate Splin (TPS)
      methods; 13 homologous landmarks type I and three type II were used. The result
      of cluster analysis indicated that these species are represented by two big
      groups: robust and thin. The uniform and non uniform components, and the
      principal warps (WP) and partial warps (Wparc), described the shape changes
      related to body depth, involving relative displacements of the appendicular
      skeleton and the cephalic region. All species were characterized by allometric
      growth with the exception of Hyphessobrycon mavro, who presented an isometry
      between the landmarks 6-7. Two new measures are proposed for species
      discrimination in the group (snout-supraoccipital spine distance and
      supraoccipital spine-pelvic fin).

PMID- 21721236
TI  - [Structure and ultrastructure of the ovary of Cichlasoma urophthalmus
      (Osteichthyes: Cichlidae)].
AB  - The study of the normal development, differentiation, structure and function of
      various components of developing follicles in the ovaries of numerous fish
      species have been a consistent focus of comparative reproduction. The structural
      and ultrastructural features of gonads from Cichlasoma urophthalmus have received
      scarce attention. In this work, we realized a descriptive study of female gonads
      of Cichlasoma urophthalmus. A total of 40 samples were collected in the Veracruz
      Alvarado Lagoon, Mexico in 2007-2008 period including the windy, dry and rainy
      seasons. Female gonads were extracted and a portion was fixed in 4% formaldehyde
      for treatment for routine histology hematoxylin and eosin (HE) and another part
      was processed for transmission electron microscopy (TEM). The gonads were fixed
      in 3% glutaraldehyde and 2% osmium tetroxide, followed by dehydrated in ethanol
      50%, 70%, 80%, 95% and 100% for inclusion in Epon, thin sections were then
      prepared and were contrasted with lead citrate and uranyl acetate. The process of
      oocyte development can be divided into five distinct stages (formation of oocytes
      from oogonia, primary growth, lipid stage, vitellogenesis and maturation). In
      this work, we found that the primary growth stage is characterized by intense RNA
      synthesis and the differentiation of the vitelline envelope. Secondary growth
      starts with the accumulation of lipid droplets in the oocyte cytoplasm (lipid
      stage), which is then followed by massive uptake and processing of proteins into
      yolk platelets (vitellogenic stage). During the maturation stage, the lipid
      inclusions coalesce into a single oil droplet, and hydrolysis of the yolk
      platelets leads to the formation of a homogeneous mass of fluid yolk in mature
      eggs. In conclusion, further studies should elucidate structure and
      ultrastructural changes in the ovarian follicular components, in C. urophthalmus
      during different stages of oocyte growth.

PMID- 21721237
TI  - [Age and growth of the hybrid tilapia Oreochromis niloticus x Oreochromis aureus
      (Perciformes: Cichlidae) in the dam "Zimapan" Mexico].
AB  - Studies on age and growth in fishes are essential to establish models on
      population dynamics. The previous issues were determined in this study by scale
      growth analyses. Between September 2003 and May 2004, 382 organisms were captured
      using gill and atarraya nets. Eight samples were developed every month a long
      this study. Standard length in centimeters (L(e)), total weight in grams (P9t)),
      scale length in centimeters (L(esc)) and growth rings were determined. The size
      and weight ranged from 38 to 232 mm (L(e)) and 8.7 to 311.9 g (P(t)),
      respectively. The growth rings analyses reveal four age groups, being the second
      group the most representative with 34.3% of the total sampled. The scale ring
      analyses showed two growth rings, one develops between November-January and the
      other between April-May, in good correlation with low temperature and gonad
      development, respectively. The growth parameters were established as: L infinity
      = 281.1mm, W infinity = 877.1g, K = 0.33 and T(0) = 0.88 year(-1). The growth
      curves based on length and weight were described by using the von Bertalanffy
      model: L(e) = 28.11[1 -e (-0.33(t+0.88))] and P(t) = 877.17[1-e (
      0.33(t+0.88))]3. Finally, it is concluded that commercial catches in this dam are
      between a year and year and half-old when exploited.

PMID- 21721238
TI  - [Postnatal growth patterns in eight species of herons and egrets (Ciconiiformes:
      Ardeidae)].
AB  - Avian postnatal growth has received considerable attention and its ecological
      implications have been deeply analyzed. In this current paper, I describe the
      patterns of culmen and tarsus growth, as well as of weight gain patterns in eight
      species of herons and egrets (Aves: Ardeidae) found in the Birama Swamp in
      Eastern Cuba. Between 1998 and 2006,714 nestlings of the following species were
      measured every two days: Butorides virescens, Bubulcus ibis, Egretta thula, E.
      tricolor, E. caerulea, E. rufescens, Ardea alba and Nycticorax nycticorax.
      Logistic and Gompertz equations were adjusted to data using non-lineal regression
      models with adult values as the asymptote. For each species, the following were
      determined and recorded: growth rate, age at inflexion, instantaneous growth
      rates at each age interval, and time taken to reach 90% of adult size. Reported
      hatchling sizes were similar in other localities, with a variation coefficient
      ranging between 10-19%. At hatch, each species exhibited differing sizes relative
      to adult values. In all cases, Gompertz equations were best fitted to explain
      more variance and lesser residuals. Rates of weight change and tarsus growth were
      alometrically related to the log of adult weight. Two main growth processes were
      identified: a physical extension in dimensions of each measurement reflecting
      inter-specific morphometric differences, and a lineal increase of the growth
      period from Green Heron to Great Egret. The Black-crowned Night Heron, Cattle
      Egret and Reddish Egret exhibited some unique measurement characteristics in
      comparison to the remaining members of the family. All results support the
      hypothesis that hypermorphosis, as the main evolutionary process in the
      microevolution of Ardeidae, is caused by a delayed final moment of growth.

PMID- 21721239
TI  - [Molecular characterization of Sigmodon hirsutus (Rodentia: Cricetidae)
      populations in Venezuela].
AB  - Recent phylogenetic studies based on cytochrome b gene sequence, have determined
      that the species historically known as Sigmodon hispidus (Rodentia) from South
      America comprises a species S. hirsutus of paraphyletic origin. The aim of this
      study was to test the hypothesis that populations from Venezuela, represent the
      sensu strict form, ancestral haplotypes, and monophyletic subspecieS. For this,
      12 individual sequences from three localities of different biogeographic regions
      in Venezuela were evaluated and sequenced based on cyto b. Additionally, the
      sequences were used to develop a cladistic analysis and genetic distance
      calculations, and to compare this information with two individual sequences of
      Sigmodon specimens available in Genbank. Phylogenetic analyses show that the
      three populations of S. hirsutus of Venezuela form an ancestral and monophyletic
      subclade supported by high bootstrap values and significant genetic distance
      between subclade within the S. hirsutus. Besides, the existence of two lineages
      suggests two subspecies, S. hirsutus hirsutus from Venezuela, and S. hirsutus
      mexicanus from Mexico-Central America, but, both species need formal description.

PMID- 21721240
TI  - [A phytosociological interpretation of vegetation from sandy hills of the
      Peruvian desert].
AB  - The vegetation of the sandy hills ("lomas") constitutes the main originality of
      the Peruvian and Chilean desert with a high number of endemics that shapes the
      vicarious associations. In this work, a phytosociological view of sandy
      environments of the Peruvian coastal desert is presented. According to the Braun
      Blanquet method, we have made up 32 phytosociological inventories and added 138
      ones from others authors. In each inventory, we have analyzed its floristic
      composition and ecological parameters, as altitude, soil and geomorphology. All
      releves were synthesized in a table to deduce the different associations, higher
      phytosociological units, and the distribu tion of its flora along the Peruvian
      coast and the Andean Cordillera. Using the Shannon-Wiener diversity index, the
      diversity of this flora is discussed making a comparison with historical data
      about the use of the territory with livestock during pre-Inca and Inca cultures,
      and Spanish invasion. As a result, two associations from Southern Peru -Nolanetum
      scaposo-spathulatae and Palauetum camanensis-weberbaueri-, two alliances 
      Nolanion humifusae from central Peru, and Nolanion spathulatae from the Southern
      Peru- and a new order -Tetragonio crystallinae-Plantaginetalia limensis- are
      described. In Nolanetum scaposo-spathulatae, Dictyophragnus englerianus,
      Leptoglossis lomana, Nolana scaposa, N. spathulata, Palaua velutina and
      Tetragonia vestita are the main characteristics, while in Palauetum camanensis
      weberbaueri association N. scaposa and P. velutina are replaced by Palaua
      camanensis and P. weberbaueri. Nolanion humifusae alliance integrates species as
      Geranium limae, Hymenocallis amancaes, Nolana humifusa, N. latipes, Palaua
      rhombifolia or Villanova oppositifolia. Likewise, Cistanthe weberbaueri,
      Cryptantha parviflora, Hoffmannseggia miranda, Lupinus mollendoensis, Nolana
      confinis, N. pallidula, N. scaposa, N. spathulata, Palaua camanensis, P.
      velutina, P. weberbaueri, Tetragonia vestita and Weberbauerella brongniartioides
      are the characteristic species of Nolanion spathulatae alliance. The Tetragonio
      crystallinae-Plantaginetalia limensis order presents characteristic plants don't
      linked with eutrophic soils, as Calandrinia alba, Cryptantha limensis,
      Dyschoriste repens, Monnina macrostachya, Oxalis lomana, Palaua malvifolia,
      Pectocarya lateriflora, Plantago limensis or Tetragonia crystallina, with a
      distribution that claps the geographical area of the new alliances. On the other
      hand, the vegetation of the desert ravines is discussed in the context of the
      coastal river plant communities and its disturbance by the dunes. After the
      application of the Shannon-Wiener diversity index on the synthetic table columns,
      we can deduce that an increase in Andean and European ruderal species is linked
      to an intensive livestock activity. The transhumance between the Andes and the
      coast from pre-Inca times until now, produces the plant dispersion of high Andean
      plants toward the coast; the Spanish colonization was the origin of the presence
      of European plants in the "lomas" vegetation of Peru.

PMID- 21721241
TI  - [Identification of marine and coastal biodiversity conservation priorities in
      Costa Rica].
AB  - Costa Rica is recognized as one of the most diverse countries in species and
      ecosystems, in their terrestrial realm as well as in the marine. Besides this
      relevance, the country presents a delay on conservation and management of marine
      and coastal biodiversity, with respect to terrestrial. For 2006, the marine
      protected surface was 5,208.8 km2, with 331.5 km of coastline, in 20 protected
      areas. The country has made progress on the conservation priority sites
      identification for terrestrial and freshwater biodiversity, with few efforts on
      marine planning. This research presents the analysis and results of the gap
      identification process, for marine and coastal biodiversity conservation in the
      protected areas system of Costa Rica. The analysis was built with the spatial
      information available on the presence and distribution of coastal and marine
      biodiversity, the establishment of the conservation goals and a threat analysis
      over the ecological integrity of this biodiversity. The selection of high
      priority sites was carried out using spatial optimization techniques and the
      superposition over the current shape of marine protected areas, in order to
      identify representation gaps. A total of 19,076 km2 of conservation gaps were
      indentified, with 1,323 km2 in the Caribbean and 17,753 km2 in the Pacific.
      Recommendations are aimed at planning and strengthening the marine protected
      areas system, using the gaps identified as a framework. It is expected that the
      results of this study would be the scientific base needed for planning and
      sustainable use of marine biodiversity in the country.

PMID- 21721242
TI  - [Distribution and density of two holothurian species in Cubagua Island,
      Venezuela].
AB  - Holothurian populations in the Caribbean have been significantly depleted in some
      areas, and others are still in danger to satisfy international markets. In
      Venezuela, this marine resource has been illegally exploited since the early
      1990s. To contribute with their management and protection, this work analyzed the
      distribution, abundance and population structure of two commercial holothurians
      Isostichopus badionotus and Holothuria mexicana in Cubagua Island shores. A total
      of 52 stations were studied around the island during the year 2008. Surveys
      included visits to each station, for which a band transect of 50 m2 with four
      replicates were carried out. The results show that I. badionotus has a higher
      distribution on the East coast of the island, and is found over Thalassia
      testudinum beds or bivalve molluscs aggregations, with an average density of
      0.011 ind/m2, C.I. 95% = 0.005-0.017, n = 122, and a general abundance estimated
      in 117 ind/ha. H. mexicana has been practically depleted (0.001 ind/m2 C.I. 95% =
      0.0002-0.0013, 7.7 ind/ha, n = 8). We recommend the maintenance of the total ban
      adopted in 1997 to assure the protection of these species, mainly because no
      previous data supported the start of the fishery, and also, because the current
      densities are still very low when compared to other areas in Venezuela and the
      Caribbean. These are animals easy to catch, susceptible to overfishing, and with
      a very low recovery rate; thus, more control is required from the local
      authorities.

PMID- 21721243
TI  - [The influence of macrophytes on rotifer and microcrustacean assemblage in a
      tropical floodplain].
AB  - Most studies on zooplankton ecology have been conducted in open waters. However,
      it has been considered of great importance to extend such studies to other
      habitats, such as those generated of macrophytes. We studied the spatial and
      temporal variation of the microcrustacean and rotifer assemblage structures
      associated with macrophytes, and compare them with the variation exhibited in
      open waters. Integrated samples were collected for zooplankton and phytoplankton
      biomass using a Schindler bottle, in four open water sites and four other sites
      covered by macrophytes in the floodplain complex of Ayapel (Cordoba, Colombia)
      during different limnimetric levels. The significant differences in the structure
      were evaluated using Kruskal & Wallis and discriminant analyses, and the
      similarity among sampling sites was evaluated using Bray & Curtis analysis.
      Zooplanktonic richness was favored by macrophytes. However, we did not find a
      constant spatial pattern for density, and only particular trends apparently
      conditionated by flood pulses. The presence of Eichhornia azurea (Pontederiaceae)
      contributed in a significant way with an increase in the diversity and density of
      benthic taxa. The density of some zooplanktonic groups was related with
      environmental conditions and phytoplanktonic biomass.

PMID- 21721244
TI  - [Ichthyofauna monitoring using higher taxa in Cabo Pulmo National Park, Mexico].
AB  - The uses of biological indicators allow to save time, resources and staff efforts
      when monitoring programs are conducted. The reef fishes are among the species
      with biggest potential as indicators since they are conspicuous, easy to identify
      in the field and have ecological and economical importance. The objective of this
      study was to evaluate the usefulness of higher taxa to predict fish ecological
      indices in Cabo Pulmo reef. We generated multiple stepwise regression equations
      with species abundance data grouped at genera and family levels as factors, and
      using ecological indices (H', J', delta*) as dependent variables. To test the
      efficiency of the models, the expected indexes were compared with those observed
      in the field during independent test surveys. Results showed that all models were
      highly significant, and the best fit occurred at genus level to H', while those
      used for delta*, based on family data level, were less precise. The proportion of
      variables required to apply prediction models of any ecological index never
      exceeded 41% of the total taxa (genera or families). In conclusion, the use of
      regression methods to determine higher taxa indicators is adequate and represents
      a good potential to be used in monitoring programs. In addition, the use of
      genera and families as indicators provide logistic benefits as training for
      monitors is less intense and expensive. Finally, the use of expected-observed
      comparisons to measure the quality of the evaluations can be useful for managers
      in order to interpret and communicate results of the scientific endeavors to the
      society, so they in turn can participate and help to improve and facilitate long
      term monitoring at Cabo Pulmo National Park.

PMID- 21721245
TI  - [Relative abundance and microhabitat use by the frog Geobatrachus walkeri (Anura:
      Strabomantidae) in two habitats of Sierra Nevada de Santa Marta, Colombia].
AB  - Geobatrachus walkeri belongs to a monotypic frog genus endemic to the San Lorenzo
      area, Sierra Nevada de Santa Marta, Colombia. This species has been categorized
      as endangered because of its small distribution area and the decline in the
      extent and quality of its habitat. It inhabits two forest types with different
      composition and structure, the native secondary forest and a pine plantation
      (dominated by Pinus patula). To compare the relative abundance and microhabitat
      use of this species in these habitat types, 30 quadrants/environment were
      distributed randomly. The individual number, microhabitat use and other aspects
      of its natural history were registered using visual encounter surveys in both
      sites, including non-sampled areas in the quadrants. The relative abundance of
      frogs was significantly different between habitats and among seasons. The highest
      abundance of G. walkeri relative to the total area was found in the pine
      plantation, being 2.3 times higher than in the natural forest. More frogs were
      significantly found during the rainy season; nevertheless, active individuals
      were also found during the dry season. Significant differences were found in the
      microhabitat use with respect to the forest type and season. The most frequently
      microhabitat used in the two forest types was the pine leaf-litter; besides, in
      the native forest, the microhabitat occupied more frequently presented medium and
      large size stones. Geobatrachus walkeri is a successful species in pine
      plantations, associated permanently to its leaf-litter environment where it seems
      to develop its entire life cycle. The clear modifications in the soils and water,
      derived from the introduction of the pine plantation in this area, seem not to
      have negatively affected the conservation and successful maintenance of this
      species.

PMID- 21721246
TI  - [Alfa and beta diversity of reptilian assemblages in Zapatosa wetland complex,
      Colombia].
AB  - Diversity is a property of community that can described, characterized, and
      understood according to the functioning of ecosystems. To study the richness and
      local abundance and species replacement between habitats around the Zapatosa's
      wetland complex (El Cesar Department), I carried out four field trips between
      November of 2006 and October of 2007. A total of 640 sampling hours/man analyzed
      five habitat types chasmophyte forest, dry forest, riparian forest, palm-grove
      and tree-lined savanna; with the exception of the palm-grove sampled at its 75%,
      the others were sampled up to their 80%. I found 847 reptiles that were
      distributed in 48 species. The group with the highest number of species was
      Colubridae with 14, followed by Gekkonidae with five. Five endemic species and
      eight with some conservation threat grade at a national level are reported. The
      riparian forest was the richest and most abundant habitat with 34 species and 196
      individuals. For each habitat, Colubridae had the highest number of species,
      followed by the families Polychrotidae, Gekkonidae and Teiidae, in that order.
      The reptile species composition was not different between the tree-lined savanna
      and the chasmophyte forest, but differed among the tree-lined savanna and the
      riparian forest, palm-grove and dry forest habitats. The most important
      differences in the species composition among almost all the habitats were
      influenced by the species Anolis tropidogaster and Gonatodes albogularis, and the
      higher occurrence of Stenocercus erythrogaster in the chasmophyte forest. The
      species replacement had an average value of 50%; the biggest amounts of shared
      species were the lizards, while the snake Leptodeira septentrionalis was the only
      one present in all habitat types. The forest grows-among-rocks showed the biggest
      complementarity and number of unique species compared to the other habitats. The
      wetland complex provides two thirds of the reptile's species reported until now
      for the Caribbean region, and more than 80% of those reported for the El Cesar
      department. This wetland complex seems to behave as a center for low land species
      concentration as it hosts a high proportion of species from those places.

PMID- 21721247
TI  - [Nationwide surveillance of parenteral antibiotics containing meropenem
      activities against clinically isolated strains in 2009].
AB  - The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics
      against clinical isolates of 2655 strains including 810 strains of Gram-positive
      bacteria, 1635 strains of Gram-negative bacteria, and 210 strains of anaerobic
      bacteria obtained from 30 medical institutions during 2009 was examined. The
      results were as follows; (1) MEPM was more active than the other carbapenem
      antibiotics tested against Gram-negative bacteria, especially against
      enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most
      of the species tested in Gram-positive and anaerobic bacteria, except for
      multidrug resistant strains including methicillin-resistant Staphylococcus aureus
      (MRSA). (2) MEPM maintained potent and stable antibacterial activity against
      Pseudomonas aeruginosa. The proportion of MEPM-resistant strains to ciprofloxacin
      resistant strains or imipenem-resistant strains were 53.1% and 58.0%
      respectively. (3) The proportion of extended-spectrum beta-lactamase (ESBL)
      strains was 3.1% (26 strains) in enterobacteriaceae. And the proportion of
      metallo-beta-lactamase strains was 2.0% (6 strains) in P. aeruginosa. (4) Of all
      species tested, there were no species except for Bacteroides fragilis group,
      which MIC90 of MEPM was more than 4-fold higher than those in our previous study.
      Therefore, there is almost no significant decrease in susceptibility of clinical
      isolates to meropenem. In conclusion, the results from this surveillance study
      suggest that MEPM retains its potent and broad antibacterial activity and
      therefore is a clinically useful carbapenem for serious infections treatment at
      present, 14 years passed after available for commercial use in Japan.

PMID- 21721248
TI  - [Epidemiology and drug susceptibility of Pseudomonas aeruginosa strains isolated
      in the Chugoku region of Japan. Infection Forum in the Chugoku Region].
AB  - Recently, there have been reports concerning an increased frequency of isolation
      of multi-drug resistant Pseudomonas aeruginosa (MDRP) strains in hospitals and
      other clinical settings as well as the associated risk of their hospital-acquired
      infections; in such a situation, it has been a major challenge to establish
      methods of managing and treating the infections. In order to investigate the
      trend of P. aeruginosa, the Infection Forum in the Chugoku Region has conducted
      to a multi-center collaborative study to isolate P. aeruginosa strains from
      sputum and urine samples collected between October 2006 and September 2008,
      analyzed the drug susceptibility and the pulsed-field gel electrophoresis (PFGE)
      patterns of each strain, and assessed epidemiologic characteristics. Of the 738
      P. aeruginosa strains collected in this study, 152 (20.6%), 179 (24.3%), 47
      (6.4%), and 39 (5.3%) were found to be ciprofloxacin-resistant, imipenem
      resistant, amikacin-resistant, and MDRP, respectively. Among the various
      antimicrobial agents tested, arbekacin (ABK) revealed the strongest inhibitory
      effects on each drug-resistant and MDRP strain; therefore, ABK was considered as
      a potential candidate for future treatment of diseases caused by P. aeruginosa.
      The study also showed that the detection rates of MDRP varied a lot from hospital
      to hospital. In addition, PFGE-based cluster analyses revealed several strains
      isolated in the same hospital exhibited a similar PFGE pattern and the same drug
      susceptibility, suggesting the presence of "unique" hospital-specific strains.

PMID- 21721249
TI  - [Mass-spectrometric measurements of P450 isoform specific content and
      corresponding enzyme activities].
AB  - Mouse cytochrome P450 subfamily 1A, 3A, 1E, 2C, 2D isoenzyme activities and
      corresponding contents were measured by means of triple quadrupole mass
      spectrometer in Multiple Reaction Monitoring mode (MRM). The technique was
      developed and tested on microsomes from control mouse and after induction with
      phenobarbital or methylcholanthrene. MRM allowed us to measure the content of
      individual P450 isoforms without using isotopic-labeled peptides or
      derivatization reagent. The results of modifying the content of certain P450
      isoforms correlated with the change of enzymatic activity, defined by marker
      substrates.

PMID- 21721250
TI  - [Data filtration for more robust alignment of chromatograms of complex peptide
      mixtures].
AB  - In carrying out proteomic researches using mass-spectrometry there often arises a
      need to compare experimental data with each other (e.g. control of pathology, the
      labeled to unlabelled samples). If for peptide identification in different
      experiments one uses only their exact mass measurements and the retention time in
      the chromatographic column, difficulties with the identification of
      chromatographic peaks belonging to the same substances in different chromatograms
      come up (retention time normalization). Due to inevitable discrepancies in
      chromatographic conditions of experiments (replacement of chromatographic
      columns, small changes in mobile phase flow rate or solvent concentration)
      retention times of the same peptides will diverge from experiment to experiment.
      In this paper we offer a reliable method for selecting peaks from mass
      chromatograms corresponding to the same peptides, which can later be used for
      retention time normalization (either linear or any other monotone function).

PMID- 21721251
TI  - [Semiconductor fluorescent nanocrystals (quantum dots) in biological biochips].
AB  - Comprehension of biological processes in cells, tissues and organisms requires
      identification and analysis of numerous biological objects, mechanisms of their
      action and regulation. Microarray (biochips) technology is a rare tool to solve
      this problem. It is based on high-throughput recognition of a target to the probe
      and has the potential to measure simultaneously the presence of numerous
      molecules in multiplexed testes, all contained in a small drop of test fluid.
      Biochips allow the parallel analysis of genomic or proteomic content in healthy
      versus disease-affected or altered tissues or cells. The signals read-out from
      the biochips is done with organic dyes which often suffer from photobleaching,
      low brightness and background fluorescence. Recent data show that the use of
      fluorescent nanocrystals "quantum dots" (QDs) allows push away these
      restrictions. The QDs are sufficiently bright to be detected as individual
      particles, extremely resistant to photobleaching and provide unique possibilities
      for multiplexing thus supplying the microarray technology with the novel read-out
      option enabling the sensitivity of detection reaching the single molecule level.
      This paper is aimed at the development of the approaches to the QDs application
      in microarray-based detection. Possibilities of QDs application both in solid
      state (planar) biochips as well as intensively developing technique of suspension
      biochips (bead-based assays or liquid biochips) are demonstrated. The latter are
      more and more applied for simultaneous identification of very large numbers of
      molecules in proteomics, genomics, drug screening and clinical diagnostics. This
      assays base on spectral encoded elements (as a rule polymer microbeads). The
      benefits of using optically encoded microbeads (instead of the solid-state two
      dimensional arrays) are derived from the freedom of bead to move in three
      dimensions. Polymeric beads optically encoded with organic dyes allow for a
      limited number of unique codes, whereas the use of semiconductor nanocrystals as
      fluorescent tags improves the beads multiplexed imaging capabilities,
      photostability and sensitivity of the biological objects detection. Additionally,
      an employment in suspension biochips of Frster resonance energy transfer (FRET)
      allows improving detection specificity. The absence of fluorescent background
      from non-interacting with the beads dye-labelled antibodies additionally
      increases the sensitivity of detection and further facilitates the multiplexing
      capabilities of nanocrystals-based detection and diagnostics. So the combination
      of the biochips and QDs techniques allow increasing detection sensitivity and
      significantly raising the number of detected objects (multiplexing capacities).
      Such combination should provide the breakthrough in proteomics, particularly in
      new drugs development, clinical diagnostics, new disease markers identification,
      better understanding of intracellular mechanisms.

PMID- 21721252
TI  - [Knowledge-based technologies in proteomics].
AB  - Proteomic technologies enable to identify thousands of proteins in biological
      samples. These data require appropriate means for storage, dissemination and
      analytical processing to decipher the new knowledge. Automatic processing of high
      efficient experiment results is powered by the controlled vocabularies, such as
      Medical Subjects Headings and GeneOntology. While ontology and vocabularies
      undergo constant evolution, it is necessary to provide the centralized storage of
      proteomic data for further revision in accordance with the updated knowledge
      domain. Proteomic repositories like PRIDE, The Global Proteome Machine,
      PeptideAtlas etc. are available to harbor the wealth of mass spectral data and
      appropriate protein identifications. The existing repositories facilitate the
      development of knowledge extraction technologies to compare the list of
      identified proteins with the GeneOntology annotations, Medical Subjects Headings,
      metabolic and regulatory pathways. This paper reviews modern analytical tools
      that exploit the knowledge-based technologies for proteome research.

PMID- 21721253
TI  - [Proteomics and peptidomics in fundamental and applied medical studies].
AB  - The review is focused on current issues of biomedical proteomics and peptidomics.
      The main attention is paid to modem proteomics technologies applied in medical
      research--extraction, detection and data analysis techniques. The use of
      chromatography, mass spectrometry and chromato mass spectrometry in
      proteogenomic, biomedical studies and biomarker discovery is discussed in detail.

PMID- 21721254
TI  - [L-[methyl-(11C)]-methionine of high enantiomeric purity production via on-line
      11C-methylation of L-homocysteine thiolactone hydrochloride].
AB  - L-[methyl-(11C)]-methionine ([11C]MET), labelled with carbon-11 (T1/2 = 20 min),
      is the most commonly used amino acid radiotracer for PET diagnostics of brain
      tumors. The production of [11C]MET via on-line 11C-methylation of L-homocysteine
      thiolactone hydrochloride (lactone) on C18 solid-phase extraction cartridge
      creates a problem of insufficient enantiomeric purity (content of L-isomer) of
      the product. The results of a systematic study of the influence of reaction
      parameters (lactone/base and the EtOH/H20 ratios, time of 11C-methylation) on the
      content of L-isomer in the preparation are presented. The developed method of on
      line [11C]MET synthesis allows to obtain a product with a sufficiently high
      radiochemical yield (75 +/- 3%, n = 100, based on [11C]CH3I) and reliably high
      content of L-isomer (93.7 +/- 0.5%) satisfying the requirements of clinical
      applications. [11C] MET synthesis was performed on a fully automated module
      designed by the Institute of Human Brain (IHB RAS).

PMID- 21721255
TI  - [Biotechnological production of acetylated thymosin beta4].
AB  - Thymosin beta4 (43 aa) is a highly conserved acidic peptide which regulates actin
      polymerization in mammalian cells by sequestering globular actin. Thymosin beta4
      is undergoing clinical trials as a drug for the treatment of venous stasis
      ulcers, corneal wounds and injuries, as well as acute myocardial infarction.
      Currently, thymosin beta4 is produced with solid-phase chemical synthesis.
      Biotechnological synthesis of this peptide presents difficulties because N
      terminal amino acid residue of thymosin beta4 is acetylated. In this study we
      propose a method for producing the recombinant precursor of thymosin beta4 and
      its subsequent targeted chemical acetylation. Desacetylthymosin beta4 was
      synthesized as a part of a hybrid protein with thioredoxin and a specific TEV
      (tobacco etch virus) protease cleavage site. The following scheme was developed
      for the purification of desacetylthymosin beta4: (i) the biosynthesis of a
      soluble hybrid protein (HP) in Escherichia coli; (ii) isolation of the HP by ion
      exchange chromatography; (iii) cleavage of the HP with TEVprotease; (iv)
      purification of desacetylthymosin beta4 by ultra-filtration. N-terminal
      acetylation of desacetylthymosin beta4 was performed with acetic anhydride under
      acidic conditions (pH 3). The reaction yield was 55%. Thymosin beta4 was then
      purified by reverse-phase high performance liquid chromatography. The proposed
      synthetic approach to recombinant thymosin beta4 is suitable for scale-up and can
      provide for the medical use of highly purified preparation with a yield of 20 mg
      from 1 L of culture.

PMID- 21721256
TI  - [Isolation and structure of novel peptide inhibitor of HIV-1 integrase from
      marine polychaetes].
AB  - A homogeneous peptide with m683 Da which inhibits HIV-1 integrase with IC50 3 x
      10(-5) M was separated from aqueous extracts of marine worm Eunicidae sp. by
      multi-stage chromatography purification. The structure Asp-Leu-Hse-His-Ala-G1n
      was proposed for this peptide according to the amino acid analysis, automated
      amino acid Edman sequencing, TLC with the witness and homoserine MS/MS
      fragmentation. The proposed structure is the first example of natural peptide
      containing amino acid homoserine residue.

PMID- 21721257
TI  - [Enhancer activity of DNA fragments from FXYD5-COX7A region of human chromosome
      19].
AB  - The enhancer activity of four previously identified within the one megabase
      region of human chromosome 19 DNA fragments was investigated. All four fragments
      had similar tissue-specific profile--maximum of enhancer activity was observed in
      HEK293 and minimum in HeLa cells. Enhancers obtained had pronounced specificity
      toward cytomegalovirus promoter compared with SV40 promoter. Functional
      dissection of one of the fragments (enhancer 14) demonstrated that only its inner
      127 b.p. part possessed enhancer activity. The negative regulators, i.e.
      silencers or insulators are probably located in flanking regions of enhancer 14
      and limit its effect on promoter. At the same time, enhancer activity of enhancer
      14 depends on its orientation relative to promoter that isn't typical to majority
      of enhancer elements. Inner 127 b.p. fragment contains 11 transcription factor
      binding sites; 8 of them are factors that take part in immune system regulation.
      Enhancer 14 is located 500 b.p. upstream of transcription start site of TYROBP
      (DAP12) gene that codes for of T-killer cells activator protein and possibly
      functions as tissue-specific enhancer for this gene.

PMID- 21721258
TI  - [Novel metabolically stable functionally-active mimetic of spermidine].
AB  - Earlier unknown 1,8-diamino-3-methyl-4-azaoctane (gamma-MeSpd) was synthesized.
      The analogue was not a substrate of ether spermine/spermidine N1
      acetyltransferase, or spermine synthase, but was capable to support the growth of
      DU145 cells with depleted polyamine pool. Such a combination of y-MeSpd
      properties discloses novel opportunities to study cellular functions of
      catabolically unstable and easily interconvertible spermine and spermidine.

PMID- 21721259
TI  - [Glycosides of hydroxylamine derivatives. I. phase transfer synthesis and study
      of isatine-3-oximes glucosaminides influence on bacterial luminescence].
AB  - In the phase transfer system solid calcium carbonate-acetonitrile, per acetate
      alpha-D-glucosaminilchloride glycosilate easily deprotoned isatine-3-oximes
      hydroxyl groups. It was found that the presence in the reaction mixture a
      catalytic amounts of 15-crown-5 accelerated the process twice. Obtained O-beta-D
      glucosaminides were identified with 1H-NMR spectroscopy. Features of synthesized
      compound's NMR spectra are discussed in comparison with those of another N
      acetylglucosamine 1-O-derivatives. The biological activity of the some oximes
      with different substituents in isatin residuum has been studied in a test of
      inhibition of bioluminescence of marine luminescent bacteria Photobacterium
      leiognathi Sh12. The nature of N-substituent of isatin fragment and 5-substituent
      of isatin main structure is compared with glycosides ability to suppress
      bacterial luminescence.

PMID- 21721260
TI  - [Oligo(2'-O-methylribonucleotides) with the insertions of 2'
      bispyrenylmethylphosphorodiamidate nucleoside derivatives as perspective
      fluorescent probes for RNA detection].
AB  - A series of novel fluorescent conjugates of oligo(2'-O-methylribonucleotides)
      containing the insertions of 2'bispyrenylmethylphosphorodiamidate derivatives of
      ribonucleosides (Urd, Cyd) were synthesized and their fluorescent properties were
      investigated. The possibility of detection of RNA transcript of 5'-terminal
      fragment of mRNA of multidrug resistance gene mdr1 (1-678) in solution using
      synthesized multipyrene probes was demonstrated.

PMID- 21721261
TI  - [Application of BODIPY-trimethylmelamine conjugate for DNA cross-linking in
      vitro].
AB  - Conjugate the fluorescent dye 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza
      s-indatsen-8-propionic acid (BODIPY) and N2,N4,N6-trimethylmelamine was obtained.
      It was shown that this compound in the presence of formaldehyde generates
      covalent cross-links of DNA strands in vitro.

PMID- 21721262
TI  - [Methoxymethyl and (p-nitrobenzyloxy)methyl groups in the synthesis of
      oligoribonucleotides by the phosphotriester method].
AB  - An efficient synthetic method for monomer ribonucleotide synthons containing 2'-O
      methoxymethyl and 2'O-(p-nitrobenzyloxy)methyl groups used for oligonucleotide
      phosphotriester method with O-nucleophilic intramolecular catalysis at the stage
      of formation of internucleotide bond is developed. It is shown that synthons
      containing protecting 2'-O-(p-nitrobenzyloxy)methyl group may be used for
      automatic synthesis of phosphotriester oligoribonucleotides with high yields and
      synthons containing methoxymethyl group--to get 2'-O-modified oligonucleotides.

PMID- 21721263
TI  - [The role of tear acidity and Cu-cofactor of lysyl oxidase activity in the
      pathogenesis of keratoconus].
AB  - Detailed analysis of copper compounds migration in the corneal stroma are
      presented. The biochemical conditions of the middle periphery of the cornea is
      found to inhibit copper ions movement to the center in patients with keratoconus
      due to increased tear alkalinity. Low concentration of dichlorocuprate (I) ion in
      the center of cornea results in inactivation of lysyl oxidase, an enzyme that
      catalyzes collagen cross-linking, and thus promotes keratoconus. Revealed
      association of tear acidity and copper distribution in cornea offers new
      opportunities in pathogenic treatment of keratoconus.

PMID- 21721264
TI  - [Comparative analysis of retinotomographic and histological examinations of
      retina in health and primary open-angle glaucoma].
AB  - Comparative analysis of retinal structure was performed in patients with POAG and
      control healthy group using spectral OCT and histology. An apparent similarity of
      tomographic and histological patterns of retinal changes was found in patients
      with POAG. These results make OCT potentially appropriate method for vital
      examination of retinal structure in glaucomatous eyes including early stages of
      the disease. Degeneration of all retinal layers is revealed. Blood flow
      deficiency due to sclerosis and hyalinosis of uveal vessels is considered to be
      an immediate cause of outer and intermediate retinal layers degeneration.

PMID- 21721265
TI  - [Up to date methods of optic nerve evaluation in patients with optic neuropathy
      of various etiology].
AB  - 132 patients (188 eyes) with proven optic neuropathy of non-glaucomatous origin
      were examined using static perimetry, visual evoked potential (flash and pattern
      types), optic coherent tomography of papilla and thickness of peripapillary nerve
      fiber layer. Sensitivity/ specificity of methods for identification of optic
      nerve diseases in acute stage were 92/75%, 92/84%, 90/92% respectively.
      Combination of these three methods let us identify optic neuropathy in 100% of
      cases, including latent forms.

PMID- 21721266
TI  - [Comparative analysis of several morphometric parameters received using optic
      coherent tomography and scanning laser ophthalmoscopy in initial glaucoma
      diagnosis].
AB  - Retinal morphometric parameters received using confocal scanning laser
      ophthalmoscopy and optic coherent tomography (OCT) are compared. OCT was
      performed using Stratus OCT 3000 ("Carl Zeiss Meditec"), and for confocal
      scanning laser ophthalmoscopy we used Heidelberg retinal tomography HRT 3.0
      ("Heidelberg Engineering"). A total of 81 patients (158 eyes) were enrolled into
      the study: 34 patients (64 eyes) with suspected glaucoma (diagnosis of early open
      angle glaucoma was proven after ophthalmologic examination) and 47 healthy adults
      aged from 38 till 72 years old. OCT was found to reveal significant decrease of
      retinal nerve fiber layer (RNFL) thickness in peripapillary zone in patients with
      suspected glaucoma as compared with healthy subjects, whereas no significant
      difference in morphometry of neuroretinal rim and PNFL was found using confocal
      scanning laser ophthalmoscopy (HRT).

PMID- 21721267
TI  - [Risk factors of extraocular spread after local treatment of uveal melanoma].
AB  - 14 cases of extraocular spread in patients with uveal melanoma after previous eye
      preserving treatment were analyzed. The time of manifestation and risk factors of
      extrascleral invasion were determined in patients after different local treatment
      modalities of uveal melanoma.

PMID- 21721268
TI  - [The value of neopterin in etiological diagnosis of endogenous uveitis].
AB  - Neopterin concentration in blood serum and tear fluid was estimated in 94
      patients with endogenous uveitis and 28 healthy subjects. Neopterin concentration
      was found to be elevated in blood serum of patients with herpetic (12,31+1,1
      micromol/L), tubercular uveitis (17,77+4,18 18 micromol/L) and uveitis associated
      with systemic conditions (12,31+1,1 micromol/L). Neopterin concentration in blood
      serum of healthy subjects was 8,45+0,61 micromol/L. Dynamics of neopterin
      concentration in blood serum of patients with uveitis varies depending on
      etiology. Neopterin concentration in tear fluid of healthy subjects appeared to
      be higher as compared with blood serum and was as high as 14,52+1,61 micromol/L
      (p < 0.05). Due to wide range of neopterin concentration in tear fluid, absence
      of significant correlation with blood serum concentration, apparently because of
      additional "local" production, authors propose to use only blood serum neopterin
      concentration for etiologocal diagnosis and control of treatment efficacy.

PMID- 21721269
TI  - [Combination of measurement of retinal vascular caliber, adaptive optics and
      fluorescent angiography in early diagnosis and monitoring of diabetic and
      hypertensive retinopathy].
AB  - 15 patients with diabetic and hypertensive retinopathy are examined. Retinal
      vascular caliber was measured using adaptive multifocal fundus camera (AMFC),
      fundus camera "Topcon" TRS-NW200 and FAG. Combination of retinal vascular caliber
      measurement and fundus foto using AMFC in patients with ametropia and
      astigmatismus showed apparently lower arteriolovenular coefficient (A VC)
      compared with that estimated using FAG imaging. Retinal vascular caliber
      measurement using adaptive optics is a highly sensitive method of visualization
      and monitoring of early signs of diabetic and hypertensive retinopathy.

PMID- 21721270
TI  - [Morphology of conjunctival changes in thyroid eye disease].
AB  - The goal of the study was to determine morphological changes of conjunctiva
      underlying positive vital staining in TED. 46 patients (92 eyes) with TED were
      included into the study. Besides routine ophthalmologic examination they
      underwent impression cytology and histology. According to our results positive
      conjunctival staining in TED is caused by punctuate epithelial erosions and
      excessive desquamation of superficial cells. Revealed changes are not specific
      for TED.

PMID- 21721271
TI  - [Visual fixation features after treatment of exudative age macular degeneration].
AB  - Changes of visual fixation in patients with choroidal neovascularitation (CNV)
      associated with age macular degeneration (AMD) after bevacizumab are studied. 45
      patients (45 eyes) with active CNV treated with intravitreal bevacizumab were
      enrolled into the study. Visual fixation was studied before and 3-6 months after
      treatment using original method that included fundus foto and fluorescein
      angiography. Fixation relative to fovea and lesion was evaluated. Foveal fixation
      beyond lesion was found in 9%, foveal fixation within lesion--in 47%, extrafoveal
      fixation beyond lesion--in 18%, extrafoveal fixation within lesion--in 26% of
      patients. Changes of fixation localization after treatment was found in 24%
      patients. Examination of visual fixation may be useful for prognosis of anti-VEGF
      treatment efficacy in patients with CNV.

PMID- 21721272
TI  - [Evaluation of stereometric parameters of optic disc and nerve fiber layer using
      HRT III. Report 1: reproducibility and intraobserver variability coefficients].
AB  - 29 patients with initial primary open angle glaucoma were examined using
      Heidelberg retinal tomograph III (HRT III). In one visit 2 observers took 2
      measurements. Intra- and interobserver errors (reproducibility and intraobserver
      variability coefficient) were calculated for 13 stereometric parameters of optic
      disc and retinal nerve fiber layer (RNFL). Rim area, cup depth (mean, maximum)
      and linear cup/disc ratios showed to be minimally variable. Cup area and volume,
      disc/cup area ratio were found to have greater variability. When performed by
      different observers (each entering his own contour) reproducibility was 1,4 fold
      lower compared with intraobserver reproducibility.

PMID- 21721273
TI  - [Evaluation of stereometric parameters of optic disc and nerve fiber layer using
      HRT III. Report 2: factors influencing reproducibility].
AB  - 29 patients with initial primary open angle glaucoma were examined using
      Heidelberg retinal tomograph III (HRT III), factors influencing measurements
      reproducibility and variability were studied. The following factors were found to
      cause outliers in stereometric parameters of the optic nerve head and retinal
      nerve fiber layer: standard reference height showing large difference of
      measurements or very high values, significant difference of scan depth, small
      optic disc, astigmatism, old age, interobserver variability of disc area (contour
      line position). Considering these factors one can determine indications for
      control examination thus improving method accuracy.

PMID- 21721274
TI  - [Evaluation of stereometric parameters of optic disc and nerve fiber layer using
      HRT II. Report 3: measurement error of spectral-domain optical coherence
      tomography compared with Heidelberg retinal tomograph III].
AB  - The aim was to study reproducibility and variability of measurements of retinal
      nerve fiber layer (RNFL) using spectral-domain optical coherence tomography
      (SOCT) and to compare with error of Heidelberg retinal tomograph (HRT). 29
      patients with initial primary open-angle glaucoma were examined using Heidelberg
      retinal tomograph III (HRT III) and SOCT (Cirrus HD-OCT). Intra- and
      interobserver errors (reproducibility and intraobserver variability coefficient)
      for mean RNFL thickness and its thickness in temporal, upper, nasal and inferior
      quadrants. Mean RNFL thickness measured with SD-OCT showed the highest intra- and
      interobserver reproducibility and minimal variability. Intraobserver variability
      coefficient was 3 times lower as compared with the best parameter measured with
      HRT (rim area) and it was 7 fold lower as compared with mean RNFL thickness
      measured with HRT. Thus study of RNFL using SD-OCT showed high reproducibility
      and low variability particularly for mean RNFL thickness. The measurement error
      of SOCT is lower as compared with HRT and provides the most accurate study of
      RNFL.

PMID- 21721275
TI  - [Comparative analysis of clinical and functional parameters in myopic patients
      depending on the type of reflexotherapeutic treatment].
AB  - The purpose of the study was to compare clinical and functional parameters in
      myopic patients depending on the type of re-flexotherapeutic treatment. The
      results after complex treatment using pharmacopuncture with biomaterial Alloplant
      showed to be the most significant.

PMID- 21721276
TI  - [How to confirm or exclude open-angle glaucoma?].

PMID- 21721277
TI  - [Controversial issues of differential diagnosis of optic nerve atrophy due to
      primary eye disease and symptomatic optic nerve atrophy].

PMID- 21721278
TI  - [Test device for estimation of viscoelactic properties of biological tissues].
AB  - The results of development of test device for estimation of viscoelactic
      properties of biological tussues are presented. Special software provides
      opportunity to make a graph representing intension within tested material. A high
      correlation between acoustic density and lens viscoelactic properties was found
      when isolated lenses after extracapsular cataract extraction were tested.

PMID- 21721279
TI  - [A case of severe eye contusion in proliferative diabetic retinopathy].
AB  - A case of successful treatment of sequelae of severe ocular trauma associated
      with proliferative diabetic retinopathy is represented. Improvement of
      electrophysiological parameters proves that this condition is not an absolute
      contraindication for surgery and sometimes not eye preserving only but functional
      effect can be achieved

PMID- 21721280
TI  - [A case of vasoocclusive retinal damage in moya-moya disease].
AB  - Retinal vessel occlusion and eye haemodynamics damage is described in moya-moya
      disease, a rare occlusive cerebrovascular condition characterized by progressing
      stenosis and occlusion of cerebral arteries with collateral development in basal
      vascular system. Data concerning neuroophthalmological features, diagnostic and
      treatment methods are presented. Necessity of MR-tomography and MR-angiography in
      ischemic retinal damage is emphasized.

PMID- 21721281
TI  - [Molecular imaging: towards an in cellulo chemistry].

PMID- 21721282
TI  - [Antifibrinolitic therapy for the treatment of massive ulcerative  gastro
      intestinal bleedings].

PMID- 21721283
TI  - [Endoscopic treatment of the stomach teratoma].

PMID- 21721284
TI  - [Laser treatment of trophic venous leg ulcers].

PMID- 21721285
TI  - [Postintubational trophic damages of larynx and trachea].

PMID- 21721286
TI  - [Modern preoperative methods of defining the viavility of muscular tissue].

PMID- 21721287
TI  - [N.N. Priorov--one of the founders of Russian traumatology and orthopedics].

PMID- 21721288
TI  - LUTS and OAB in men: gender matters.

PMID- 21721289
TI  - Christopher M. Cashman, CEO, SANUWAVE Health, Inc. Interview by Chimere G.
      Holmes.

PMID- 21721290
TI  - Pedaling a mission.

PMID- 21721291
TI  - How is evidence used for planning, implementation and evaluation of health
      promotion? A global collection of case studies.

PMID- 21721292
TI  - Effectiveness of health promotion in preventing tobacco use among adolescents in
      India: research evidence informs the National Tobacco Control Programme in India.
AB  - This case study has two aims. First, it describes intervention strategies from
      two school-based programs designed to prevent tobacco use among adolescents in
      India. Second, it explains how evidence from randomized controlled trials of
      these intervention programs was used by a local non-governmental organization in
      Delhi to advocate for scaling up the Government of India's tobacco control
      efforts to include school health interventions as one of the components of
      India's National Tobacco Control Program. This case study illustrates the need
      for developing countries to conduct rigorous evaluation in order to provide
      context-relevant evidence prior to scaling up interventions.

PMID- 21721293
TI  - The Bolsa Familia (family grant) program in Manguinhos: challenges and lessons
      learned in a case study: implementation process: development of strategies and
      evidence.
AB  - This article discusses the results of an evaluation research on the
      implementation of the Bolsa Familia, a conditional cash program targeted at poor
      families in Manguinhos, Brazil. The program pursues two main objectives: reducing
      current poverty and promoting human capital through the increased utilization of
      educational and health services. Connecting different agencies and stakeholders
      and building capacity for collaboration are two strategies associated with
      program effectiveness. Implementation evaluation showed that in Manguinhos, there
      were large gaps concerning the action's adequacy in relation to the specific
      implementation context, intersectoral collaboration and shared knowledge.
      Evidence from this research was used to spearhead concrete changes in policy at
      the local level.

PMID- 21721294
TI  - Tackling inequity through a Photovoice project on the social determinants of
      health: translating Photovoice evidence to community action.
AB  - St. Jamestown is the most densely populated vertical immigrant-receiving urban
      neighbourhood in Canada. The Photovoice project engaged and empowered immigrant
      residents of St. Jamestown to influence public policy and secure improved local
      services for promoting health and well-being. Twenty-seven residents used
      photography and storytelling to record neighbourhood characteristics and their
      implications on residents' health and well-being. Eight participants presented
      recommendations actionable at neighbourhood level to the councillor and worked
      with the city to carry out the recommendations made that were recognized as
      important for neighbourhood residents' health and well-being. The results
      indicate Photovoice can be used to generate dialogue on community concerns and
      priorities and promote community action.

PMID- 21721295
TI  - Spilt milk: an inter-sectoral partnership that failed to advance milk security
      for low-income lone mothers in Nova Scotia, Canada.
AB  - Canadian agricultural policy supports higher milk prices. Consequently, poor
      families lack sufficient funds to purchase adequate quantities of milk. Low
      income lone mothers in the Canadian province of Nova Scotia suggested their
      preferred strategies for improved access to milk. We then built inter-sectoral
      support for a policy intervention to address their recommendations. Our research
      to-action process led to a policy dialogue focusing on an electronic smart card
      that would permit the delivery of lower-priced milk to poor households. While all
      agreed that milk insecurity was an important issue, the project ultimately failed
      because of the entrenched positions of influential stakeholder groups.

PMID- 21721296
TI  - Scientific evidence and policy change: lowering the legal blood alcohol limit for
      drivers to 0.08% in the USA.
AB  - The United States (US) Centers for Disease Control and Prevention (CDC), and key
      partners conducted a systematic review of the effectiveness of 0.08% blood
      alcohol concentration (BAC) laws on alcohol-related traffic mortality. Review
      findings of strong evidence of effectiveness were presented by partners during US
      Congressional hearings contributing to the passage of a bill requiring states to
      lower the legal BAC limit to 0.08% (80 mg of alcohol/100 ml of blood) or lose a
      portion of their federal highway funds. The bill was signed into law, making 0.08
      the new national standard. Extensive and targeted dissemination of the evidence
      and recommendations to key stakeholders and partners built support for policy
      change at the state level.

PMID- 21721297
TI  - Neighbors Connected: the interactive use of multi-method and interdisciplinary
      evidence in the development and implementation of neighbors connected.
AB  - Neighbors Connected is a community-based intervention in the Netherlands. It
      helps the active older people to organize social activities for their less active
      older neighbors, facilitated by practical and financial support from the
      Community Health Service. The intervention is the outcome of a combination of
      semi-structured interviews with the older people, with organizations for older
      people and with local policy-makers, epidemiological data and interactive
      discussions, all of which support the notion that engaging in social activities
      is a way to enhance healthy ageing within the community. The use of different
      sources of evidence resulted in a comprehensive picture and actionable local
      knowledge.

PMID- 21721298
TI  - Movement as Investment for Health: integrated evaluation in participatory
      physical activity promotion among women in difficult life situations.
AB  - Movement as Investment for Health (Bewegung als Investition in Gesundheit or BIG)
      was a multidimensional research study in participatory physical activity
      promotion among socially disadvantaged women in a deprived neighbourhood in
      Erlangen, Germany. It aimed at making full use of health-promoting effects of
      movement and developing integrated evaluation through approaches from different
      disciplines. We defined the target population through national health survey
      data, and determined important intervention and evaluation dimensions through
      meta-analyses. A co-operative planning group of women, researchers, policy
      makers, and local experts made decisions on the most appropriate procedures.
      Integrated evaluation in participatory approaches is promising. It calls for
      context-specific evaluation, requires adaptation of existing approaches or even
      development of its own evidence base.

PMID- 21721299
TI  - The Battle River Project: school division implementation of the health-promoting
      schools approach: assessment for learning: using student health and school
      capacity measures to inform action and direct policy in a local school district.
AB  - The Battle River Project (BRP) is a school division-level intervention in rural
      Alberta, Canada, built upon the health-promoting schools approach to health
      promotion. Using self-reported school and student-level data from administrators
      and students, the central aim of the BRP is to examine: 'How can the school
      environment and health behaviours (healthy eating, physical activity and mental
      wellness) of children and youth be improved when a health-promoting schools
      model, the Ever Active Schools program, is implemented with school division
      support?' Evidence used to inform school level changes included students'
      demographic, behavioral, and psychosocial variables linked to school environment
      data, comprised of school demographics and administrator-assessed quality of
      policies, facilities, and programs related to physical activity. Each
      participating school and the division were provided with a tailored report of
      their schools' results to reflect, plan and implement for positive health
      behavior change. The main lesson learned was that sharing school-specific
      evidence can operate as a catalyst for embedding health promoting policy and
      practices within the school and division culture.

PMID- 21721300
TI  - Environmental and policy approaches to increasing physical activity: improving
      access to places for physical activity and dissemination of information.
AB  - The Centers for Disease Control and Prevention's (CDC) Racial and Ethnic
      Approaches to Community Health (REACH) program funded 40 communities in the
      United States during 1999-2007. Three of these communities implemented
      interventions to increase physical activity among African Americans. This case
      study looks at these interventions and the evidence-based recommendations from
      the CDC's Community Guide for Preventive Services. These recommendations address
      creating or improving access to physical activity and the dissemination of
      information via media campaigns. Findings suggest that although the evidence
      could not be applied in every respect, culturally-tailored change strategies can
      meet unique characteristics of African Americans with or at risk for heart
      disease and may contribute to increased physical activity.

PMID- 21721301
TI  - Pilot Health Promoting Hospital in rural South Africa: evidence-based approach to
      systematic hospital transformation.
AB  - This project aimed at transforming a rural District Hospital in the Limpopo
      Province of South Africa into a Health Promoting Hospital according to standards
      developed by WHO-Europe. The intervention used a diagnostic approach and baseline
      needs assessment of hospital staff, patients, and their relatives to identify
      health education and promotion needs. Activities included empowerment training
      and skills development, implementation of health education and promotion
      activities, and the integration of health-promoting standards and values in the
      hospital structure and culture. The project indicated applicability of the model
      in a resource-limited setting, based on staff empowerment, local leadership, and
      stakeholder engagement.

PMID- 21721302
TI  - Refuah Shlema: a cross-cultural programme for promoting communication and health
      among Ethiopian immigrants in the primary health care setting in Israel: evidence
      and lessons learned from over a decade of implementation.
AB  - The Refuah Shlema programme was established to reduce health disparities, promote
      health literacy and health indicators of the Ethiopian immigrant community in
      Israel, and included: (i) integrating Ethiopian immigrant liaisons in primary
      care as inter-cultural mediators; (ii) in-service training of clinical staff to
      increase cultural awareness and sensitivity; and (iii) health education community
      activities. Qualitative and quantitative evidence showed improvements in: (i)
      clinic staff-patient relations; (ii) availability and accessibility of health
      services, and health system navigation without increasing service expenditure;
      (iii) perception of general well-being; and (iv) self-care practice with regards
      to chronic conditions. Evidence significantly contributed to sustaining the
      programme for over 13 years.

PMID- 21721303
TI  - Let's Get Moving: a systematic pathway for the promotion of physical activity in
      a primary care setting: Let's Get Moving was developed based on National Guidance
      on effective interventions on physical activity released in the United Kingdom in
      2006.
AB  - Let's Get Moving (LGM) represents a structured approach to physical activity
      promotion in the primary care setting in the United Kingdom. LGM was developed
      based on a systematic review which recommended the use of key strategies to
      support behaviour change, including: a short counselling session; written
      educational resources; and follow-up support. These findings provided the basis
      for the programme components and the specific protocols were refined in
      consultation with a representative group of health professionals. Key learning
      centred on how to translate the scientific evidence into a practical intervention
      in routine primary care practice.

PMID- 21721304
TI  - No germs on me: a social marketing campaign to promote hand-washing with soap in
      remote Australian Aboriginal communities.
AB  - A social marketing campaign promoting hand-washing with soap was implemented to
      reduce the high burden of infection experienced by Australian Aboriginal children
      living in remote communities. Epidemiological evidence of effect and other
      evidence were used to identify the hygiene intervention and health promotion
      approach for the project. We drew on the findings of: (i) a systematic literature
      review to identify the intervention for which there is strong effect in similar
      populations and contexts; and (ii) a narrative literature review to determine our
      health promotion approach. This process provided practitioners with confidence
      and understanding so they could address a complex problem in a politically and
      otherwise sensitive context.

PMID- 21721305
TI  - Action in Childcare Settings training programme: development of an evidence-based
      training programme for the prevention of child maltreatment.
AB  - The intervention is a train-the-trainer programme for childcare practitioners
      aimed at preventing the maltreatment of young children in Quebec. The content of
      the programme was determined based on systematic reviews of published evidence on
      the issue. A number of training sessions were subsequently offered to
      practitioners in the targeted settings and rigorously evaluated. Lessons learned
      included: the importance of a needs assessment for adequate knowledge transfer to
      end users; train-the-trainers programmes are effective for transferring evidence
      to large groups; and training participants' perception of the value of evidence
      depends on the confidence inspired by those who transmit it.

PMID- 21721306
TI  - Oral health promotion for children with disabilities in the Republic of Ireland:
      independent qualitative evaluation of a multi-sectoral oral health promotion
      intervention for children with disabilities.
AB  - Children with disabilities are a marginalized group in relation to health in the
      Republic of Ireland, and oral health is frequently relegated to a position of
      little or no importance by parents, paid carers, and non-dental professionals.
      Subsequently, there is often a higher need for treatment and inpatient procedures
      that could be prevented. Introducing a health promotion intervention which aimed
      to reduce the need for dental treatment was envisioned as being the way forward.
      A qualitative evaluation of the context for implementation highlighted barriers
      in achieving the aims of the plan.

PMID- 21721307
TI  - Case study of the use of evaluation evidence to inform diabetes prevention
      programming in two Canadian health regions: effectiveness of evaluation evidence.
AB  - This study compares the use of evidence in two 18-month Canadian projects with a
      similar goal: improved prevention of type II diabetes in women from ethno
      cultural communities with a gestational diabetes diagnosis. Evidence used for
      both projects included epidemiological data and research literature, needs
      assessments with the target population, and project evaluations. Contexts for the
      use of evidence differed between the two projects in terms of the innovation and
      its level of complexity; organizational context and system readiness for change;
      and partnership characteristics. This study showed that while evidence played
      some role in determining project success, it was but one factor in deciding how
      project activities were (or were not) sustained.

PMID- 21721308
TI  - Evidence-based health promotion: an emerging field.
AB  - There is much debate around the use of evidence in health promotion practice.
      This article aims to sharpen our understanding of this matter by reviewing and
      analyzing the 26 case studies presented in this special issue. These case studies
      suggest that health promotion practitioners are using a wide range of research
      evidence in interventions for high-risk individuals, entire populations, and
      vulnerable groups according to all five strategies for action described in the
      Ottawa Charter for Health Promotion. In nearly every case, practitioners had to
      mediate and adapt research evidence for their case. Eight key levers helped
      practitioners embed research evidence into practice: local and cultural relevance
      of the evidence, community capacity-building, sustained dialogue from the outset
      with all stakeholders, established academic-supported partnerships, communication
      that responds to organizational and political readiness, acknowledgement and
      awareness of gaps between evidence and practice, advocacy, and adequate earmarked
      resources. These case studies provide some evidence that there is an evidence
      based health promotion, that this evidence base is broad, and that practitioners
      use different strategies to adapt it for their case.

PMID- 21721309
TI  - [An advocacy strategy to favor the adoption of a provincial public policy on
      smoking reduction: a public campaign which emphasizes epidemiologic portraits of
      tobacco use, studies on the impact of smoking reduction measures, and reports on
      the activities of the tobacco industry].

PMID- 21721310
TI  - [The building of the town network in health of Pernambouc in Brazil: an example
      of scaling].

PMID- 21721311
TI  - [HIV prevention among marginal groups: the case of homosexuals in Togo].

PMID- 21721312
TI  - [A participatory evaluation confirms the social relevance of a community
      intervention model in school success: consequences of the participation for the
      intervention].

PMID- 21721313
TI  - [Improving financial access of health care in Burkina Faso: a research strategy
      potentially favorable for the use of conclusive data].

PMID- 21721314
TI  - [Evidence in public health, something more than data and information - social
      change engine: analysis of the health status and social determinants for the
      development of the municipal public health policy in Cali].

PMID- 21721315
TI  - [Network for the prevention of aggression and strengthening of citizen
      competencies, Medellin, Colombia, 2006-2007: a way to complement the Project on
      Early Prevention of Aggression, Medellin, 2000-2005, according to evaluations and
      research].

PMID- 21721316
TI  - [Atraumatic restorative treatment, as part of a basic package of oral health
      services in rural areas of Bolivia: evidence on the effectiveness of atraumatic
      restoration treatment implementation and of oral health promotion measures among
      6-14 year-old students, in rural areas with dispersed population].

PMID- 21721317
TI  - Crush point: when large crowds assemble, is there a way to keep them safe?

PMID- 21721318
TI  - Cooperation in USDA studies and evaluations, and full use of federal funds in
      nutrition assistance programs nondiscretionary provisions of the Healthy, Hunger
      Free Kids Act of 2010, Public Law 111-296. Final Rule.
AB  - This final rule incorporates into the regulations governing the Programs
      authorized under the Richard B. Russell National School Lunch Act (NSLA) and the
      Child Nutrition Act of 1966 (CNA) two nondiscretionary provisions of the Healthy,
      Hunger-Free Kids Act of 2010 (HHFK Act). The HHFK Act requires State and local
      cooperation in Department of Agriculture studies and evaluations related to
      Programs authorized under the NSLA and the CNA. The HHFK Act also amends the NSLA
      to stipulate that Federal funds must not be subject to State budget restrictions
      or limitations, including hiring freezes, work furloughs, and travel
      restrictions. This final rule amends regulations for the National School Lunch
      Program; the Special Milk Program for Children; the School Breakfast Program; the
      Summer Food Service Program; the Child and Adult Care Food Program; State
      Administrative Expense Funds ; the Special Supplemental Nutrition Program for
      Women, Infants and Children; and the WIC Farmers' Market Nutrition Program. These
      provisions will strengthen program integrity by ensuring that sufficient data is
      made available for studies and evaluations. Additionally, exempting Federal funds
      from State budgetary restrictions or limitations is intended to increase the
      ability of State agencies to administer USDA's nutrition assistance programs
      effectively.

PMID- 21721319
TI  - Effects of "natural" water and "added" water on prediction of moisture content
      and bulk density of shelled corn from microwave dielectric properties.
AB  - Dielectric properties of samples of shelled corn of "natural" water content and
      those prepared by adding water were measured in free space at microwave
      frequencies and 23 degrees C. Results of measurements of attenuation, phase shift
      and dielectric constant and loss factor at 9 GHz show no difference between the
      samples with "natural" water and those in which water was added artificially.
      Bulk densities and moisture contents predicted from calibration equations
      expressed in terms of dielectric properties of both natural and added water
      samples agreed closely, and standard errors were less than 1% for moisture
      content and relative error for bulk density was less than 5%.

PMID- 21721320
TI  - Microwave discharge electrodeless lamps (MDEL). V. Microwave-assisted photolytic
      disinfection of Bacillus subtilis in simulated electroplating wash wastewaters.
AB  - This short article examines the microwave-assisted photolytic disinfection of
      aqueous solutions contaminated by Bacillus subtilis microorganisms using UV and
      vacuum-UV radiation emitted from a microwave discharge electrodeless lamp (MDEL),
      a device containing a Hg/Ar gas-fill that was proposed recently for use in
      Advanced Oxidation Processes (AOPs). Results of the disinfection are compared
      with those obtained from UV radiation emitted by a low-pressure electrode Hg lamp
      and by an excimer lamp. Also examined is the disinfection of B. subtilis aqueous
      media that contained Au3+ or Ni2+ ions, species often found in the treatment of
      electroplating wash wastewaters.

PMID- 21721321
TI  - Wireless data transmission from inside electromagnetic fields.
AB  - This paper describes analytical and experimental work developed to evaluate the
      effects of the electromagnetic fields produced by high-voltage lines (400 kV) on
      wireless data transmission at the 900MHz band. In this work the source of the
      data transmission is located inside the electromagnetic field and the reception
      station is located at different distances from the power lines. Different
      atmospheric conditions are considered.

PMID- 21721322
TI  - Fundamentals of dielectric properties measurements and agricultural applications.
AB  - Dielectrics and dielectric properties are defined generally and dielectric
      measurement methods and equipment are described for various frequency ranges from
      audio frequencies through microwave frequencies. These include impedance and
      admittance bridges, resonant frequency, transmission-line, and free-space methods
      in the frequency domain and time-domain and broadband techniques. Many references
      are cited describing methods in detail and giving sources of dielectric
      properties data. Finally a few applications for such data are presented and
      sources of tabulated and dielectric properties data bases are identified.

PMID- 21721323
TI  - Particle-in-Cell (PIC) simulation of CW industrial heating magnetron.
AB  - Modern CW industrial heating magnetrons are capable for producing as high as 300
      kW of continuous-wave microwave power at frequencies around 900 MHz and are sold
      commercially [Wynn et al., 2004]. However, to utilize these magnetrons in some
      specific research and scientific applications being of interest for the Air
      Force, the necessary adaptation and redesign are required. It means that the
      detailed knowledge of principles of their operation and full understanding of how
      the changes of the design parameters affect their operational characteristics are
      necessary. We have developed and tested computer model of a 10-vane high-power
      strapped magnetron, which geometrical dimensions and design parameters are close
      to those of the California Tube Laboratory's commercially produced CWM-75/100L
      tube. The computer model is built by using the 3-D Improved Concurrent
      Electromagnetic Particle-in-Cell (ICEPIC) code. Simulations of the strapped
      magnetron operation are performed and the following operational characteristics
      are obtained during the simulation: frequency and mode of magnetron oscillations,
      output microwave power and efficiency of magnetron operation, anode current and
      anode-cathode voltage dynamics. The developed computer model of a non
      relativistic high-power strapped magnetron may be used by the industrial
      magnetron community for designing following generations of the CW industrial
      heating high-power magnetrons.

PMID- 21721324
TI  - Microwaves & metals.

PMID- 21721325
TI  - Fundamentals and applications of microwave heating of metals.
AB  - As the fundamentals of microwave (MW) interaction with metals, boundary
      conditions of electromagnetic (EM) field on metal surface are discussed, which
      consider the EM field in the metal surface layer in terms of surface impedance.
      Experimental report on heating behavior of separated electric (E-) and magnetic
      (H-) fields of metal particles and films are shown. Temperature peak formation at
      the first heating curves was observed in both cases, which are discussed
      considering the microstructural alteration by MW heating. In the last half
      section, various reports on MW heating of metal are reviewed. They were
      classified into the major application for sintering and materials fabrication.
      And also, its usage as a heating aid of glasses and soils, topics on metal
      hydride and catalytic metal particles are included.

PMID- 21721326
TI  - Characteristics of aluminum and magnesium based nanocomposites processed using
      hybrid microwave sintering.
AB  - Powder metallurgy is one of the highly established methods to synthesize metals,
      alloys and composites. Sintering is one of the important steps in powder
      metallurgy methodology and is usually realized through conventional resistance
      furnaces. The sintering usually takes a few hours to realize density in excess of
      90%. The present study highlights the use of energy efficient and environment
      friendly microwave sintering route to synthesize pure aluminum, magnesium and
      magnesium based nanocomposites. Three reinforcements were targeted: a) silicon
      carbide, a microwave susceptor, b) alumina, a microwave transparent material and
      c) copper, a conducting material. Composites were prepared using blend - compact 
      microwave sintering - extrusion methodology. Process evaluation revealed that
      microwave assisted sintering can lead to a reduction of 86% in sintering time and
      energy savings of 96% when compared to conventional sintering. Moreover,
      microwave assisted sintering of metal compacts in this study was carried out in
      air, in the absence of any protective atmosphere, without compromising the
      mechanical properties of the materials. Results revealed that properties of
      magnesium can be convincingly enhanced using the said processing methodology and
      the materials formulations selected. Most importantly, the study established the
      viability of microwave sintering approach used in place of conventional sintering
      for magnesium based formulations.

PMID- 21721327
TI  - Microwave sintering of refractory metals/alloys: W, Mo, Re, W-Cu, W-Ni-Cu and W
      Ni-Fe alloys.
AB  - Refractory metals and alloys are well known for their high mechanical properties
      which make them useful for wide range of high temperature applications. However,
      owing to the refractoriness of these metals and alloys, it is very difficult to
      consolidate them under moderate conditions. Conventional P/M processing is a
      viable sintering technique for these refractory metals. One of the constraints in
      conventional sintering is long residence time which results in undesirable
      microstructural coarsening. This problem gets further aggravated when using
      smaller (submicron and nano) precursor powder sizes. Furthermore, conventional
      heating is mostly radiative, which leads to non-uniform heating in large
      components. This review article describes recent research findings about how
      these refractory metals and alloys (W, Mo, Re, W-Cu, W-NiCu and W-Ni-Fe) have
      been successfully consolidated using microwave sintering. A comparative study
      with conventional data has been made. In most cases, microwave sintering resulted
      in an overall reduction of sintering time of up to 80%. This sintering time
      reduction prevents grain growth substantially providing finer microstructure and
      as a result better mechanical properties have been observed.

PMID- 21721328
TI  - Microwave assisted combustion synthesis of non-equilibrium intermetallic
      compounds.
AB  - A simplified model of the microwave-assisted combustion synthesis of Ni and Al
      metal powders to form the NiAl intermetallic on titanium and steel substrates is
      presented. The simulation couples an electro-thermal model with a chemical model,
      accounting for local heat generation due to the highly exothermic nature of the
      reactions between the powders. Numerical results, validated by experimental
      values, show that the capability of microwaves to convey energy, and not heat,
      can be used to alter the temperature profiles during and after the combustion
      synthesis, leading to unique intermetallic microstructures. This phenomenon is
      ascribed to the extended existence of high temperature liquid intermetallic
      phases, which react with the metallic substrates at the interface. Moreover,
      microwave heating selectivity allows to maintain the bulk of the substrate
      metallic materials to a much lower temperature, compared to combustion synthesis
      in conventionally heated furnaces, thus reducing possible unwanted
      transformations like phase change or oxidation.

PMID- 21721329
TI  - Sintering of CuO and ZnO in a single mode microwave cavity with shrinkage
      control.
AB  - A specific TE10m microwave cavity has been designed to follow-up the shrinkage
      during the microwave sintering of ceramics powders using an optical based
      position sensing device. The basic principle consists in measuring the distance
      from a laser source to the sample surface by means of a triangulation method. The
      spatial resolution device is around a few micrometers that enables to accurately
      measure the shrinkage versus time of a microwave irradiated sample. The shrinkage
      curves have been recorded during the direct microwave sintering of CuO and ZnO.
      Sintering kinetics has been found extraordinarily fast as only a few seconds are
      needed to achieve the maximum shrinkage for both materials. This new method is
      undoubtedly powerful to increase our understanding of microwave sintering and
      very useful to control the microstructure of microwave sintered ceramics.

PMID- 21721330
TI  - Medical applications: the ISM band.

PMID- 21721331
TI  - Energy transition for depolarized backscatter from rough surfaces.
AB  - In this paper we study the depolarized backscatter enhancement phenomenon for
      electromagnetic wave scattering from rough surfaces. Some new experimental data
      on light scattering from rough metallic surfaces shows a phenomenon of
      backscattering enhancement existing in the antispecular direction under some
      conditions, such as the surface parameters, wave polarization and operating
      frequency. From a roughly random surface the backscattering enhancement is
      predicted due to the constructive interference of multiple surfaces scattering.
      The study is based upon the integral equation method modified to be able to
      predict the phenomenon of multiple scattering and backscattering enhancement.
      From the study we found the backscattering enhancement takes place on the
      specialized surface parameters large compared with the incident wavelength.
      Further we also conclude that the depolarized multiple scattering makes much
      contribution along the plane of incidence from random rough surfaces, but
      depolarized single scattering makes little contributions as our expectation. In
      comparison of model prediction of total multiple scattering strength with
      measured data along the specular plane, excellent agreement is obtained.

PMID- 21721332
TI  - Diagnostic value of microwaves in neurological disorders.
AB  - Lumbar puncture is a key diagnostic investigation in neurological diseases. The
      effect of microwaves on various biological tissues is an active area of research.
      This study describes a novel in-vitro method of cerebrospinal fluid (CSF)
      analysis using microwaves. AIM: To analyze normal and abnormal samples of CSF
      using microwave in the frequency range 2-3 GHz and to compare the variation of
      dielectric parameters of the CSF in the above frequency. MATERIALS AND METHODS:
      CSF of 34 patients admitted in the internal medicine ward during a six months
      period was analyzed for cells, protein and sugar content. The effect of
      microwaves on the CSF was measured using cavity perturbation technique and the
      dielectric properties in 2-3 GHz range were studied and compared. CONCLUSIONS:
      Microwaves, at frequencies of 2437 MHz, 2682 MHz and 2968 MHz, using the cavity
      perturbation technique can be used as a potential diagnostic tool in the analysis
      of CSF in diseases of the central nervous system.

PMID- 21721333
TI  - Visualization of microwave energy distribution in a multimode microwave cavity
      using CoCl2 on gypsum plates.
AB  - This study provides a facile method to map the microwave field distribution in a
      multimode microwave cavity. Anhydrous calcium sulfate powder was used to make the
      gypsum plates that were used as the carrying medium. Cobalt chloride hexahydrate,
      whose color changes when losing part or all of its crystal waters, was selected
      as an indicator of the energy absorption. The cobalt chloride aqueous solution at
      a concentration of 1.6% was absorbed by the dried gypsum plates. After
      introducing the plates into a microwave field, those areas that receive more
      microwave energy were preferably heated, resulting in the release of the moisture
      and consequently the loss of crystal water from the cobalt chloride hexahydrate.
      The color change on the plate formed a color map indicating the microwave field
      distribution. This method was used to investigate the energy distribution of a
      microwave oven by placing single or multiple plates in horizontal or vertical
      positions at different locations in the cavity.

PMID- 21721334
TI  - Microwave initiated atomic spectra from select atomic species.
AB  - Isotopes of gaseous Helium (3He and 4He) were admitted into the vacuum system at
      various pressures and allowed to stabilize. Quantum states were then energized
      using a 2.45 GHz magnetron coupled to the gases by loose coupling. A residual gas
      analyzer Model 100 series manufactured by Stanford Research Systems was used to
      determine the massof each species. An Ocean Optics Optical Spectrometer model
      collecting the light via an optic probe was used to obtain the spectra and to
      characterize the spectroscopic peaks. The data collected from these isotopes
      represent characteristic spectral emission lines generated due to the transitions
      among discrete quantum energy levels. The data analysis, especially for atomic
      spectroscopy, becomes an extremely important tool in developing an understanding
      of the quantum levels active within each atom. In this paper is presented a
      summary of the analysis of work that was done on two isotopes of helium. Data
      using both computational as well as theoretical techniques are presented.
      Traditional high voltage arc discharge data were taken for the gas species and
      these are compared with microwave stimulated atomic emissions.

PMID- 21721335
TI  - Density-independent high moisture content measurement using phase shifts at two
      microwave frequencies.
AB  - Density-independent high moisture content measurement is required in actual
      production line. In this paper, the experimental results for high moisture
      content measurement using microwave free-space technique are presented. The
      method is based on a ratio of phase shifts at two microwave frequencies after
      propagating through a sample. The experiments were performed with three kinds of
      sawdust named Momizai, Cedar and Douglas Fir. In the high moisture content above
      130%, the root mean square error (RMSE) of moisture determination by the method
      for three kinds of sawdust are 9.0%, 17.0%, 22.8%, respectively.

PMID- 21721336
TI  - Structure and compositional characteristics of caniniform dental enamel in the
      tuatara Sphenodon punctatus (Lepidosauria: Rhynchocephalia).
AB  - OBJECTIVE: The evolution of dental tissues in relation to tooth function is
      poorly understood in non-mammalian vertebrates. We studied the dentition of
      Sphenodon punctatus, the sole remaining member of the order Rhynchocephalia in
      this light. METHODS: We examined 6 anterior maxillary caniniform teeth from adult
      Sphenodon by scanning electron microscopy, nano-indentation and Raman
      spectroscopy. RESULTS: The elastic modulus (E) for tuatara enamel was 73.17 (sd,
      3.25) GPa and 19.52 +/- 0.76 Gpa for dentine. Hardness (H) values for enamel and
      dentine were 4.00 (sd, 0.22) and 0.63 +/- 0.02 Gpa respectively. The enamel was
      thin (100 gm or less), prismless and consisted of grouped parallel crystallites.
      Incremental lines occurred at intervals of about 0.5 to 1 rm. There were tubular
      structures along the enamel dentine junction running from the dentine into the
      inner enamel, at different angles. These were widened at their base with a
      smooth, possibly inorganic lining. Enamel elastic modulus and hardness were lower
      than those for mammals. CONCLUSIONS: The presence of enamel tubules in the basal
      part of the enamel along the EDJ remains speculative, with possible functions
      being added enamel/dentinal adhesion or a role in mechanosensation.

PMID- 21721337
TI  - New Zealand's oral health students--education and workforce implications.
AB  - OBJECTIVES: To obtain background information on the Oral Health (OH) students at
      Auckland University of Technology (AUT) and the University of Otago in order to
      aid in the recruitment of students; to determine the extent of the students'
      professional knowledge; and to determine their future employment preferences.
      METHOD: Cross-sectional survey of all OH students at AUT and the University of
      Otago in 2008. A questionnaire was given to all 165 OH students at both
      Universities, and the response rate was 100%. RESULTS: Most students came from
      Cities. Prior to commencing their OH course, they had been engaged in full-time
      work, in tertiary education or at school. Their main sources of information about
      the courses were websites, the Universities, friends and dental practitioners.
      The students' professional knowledge improved significantly as they progressed
      through the OH courses. Students were likely to want to return to work in the
      type of community that they had come from. Most (90.3%) would consider working in
      private practice, while 56.4% would consider working for the School Dental
      Service (SDS). Overall, 49.7% of students would consider working in both
      environments. CONCLUSION: This study provides information on recruitment of
      students into OH courses, and the OH students' preferences for employment after
      graduation. The findings have implications for OH education and workforce
      planning in New Zealand.

PMID- 21721338
TI  - Infant oral mutilation: a New Zealand case series.
AB  - Infant oral mutilation is a practice performed by traditional healers in many
      Eastern African countries. The sequelae of this practice have been recognised and
      reported on in many developed countries due to the migration of populations,
      customs and beliefs. This article describes three cases of infant oral mutilation
      that have been diagnosed in the Dental Department at Hutt Hospital, Lower Hutt.

PMID- 21721339
TI  - The introduction of implant dentistry in the South Pacific Islands of Fiji.

PMID- 21721340
TI  - Politicizing aid: healthcare provision and strategic objectives.

PMID- 21721341
TI  - The radio: a tool for violence prevention in Jos, Nigeria.

PMID- 21721342
TI  - Nuclear abolition: for a future.

PMID- 21721343
TI  - The Holdstock-Piachaud prize 2010.

PMID- 21721344
TI  - Climate change-induced conflict: a threat to human health.

PMID- 21721345
TI  - Health, peace, conflict: challenges for maternal and child health in the occupied
      Palestinian territories.

PMID- 21721346
TI  - Border-controlled health inequality: the international community's neglect of
      internally displaced persons.

PMID- 21721347
TI  - Health, stabilization and securitization: towards understanding the drivers of
      the military role in health interventions.
AB  - In the post-Cold War world, health issues have become firmly rooted in state
      foreign policies through initiatives such as the UK's 'Health is Global'
      strategy. However, since 9/11, there has also been growing interest in the
      interactions between health sector interventions and state fragility. Whilst
      fragility clearly has a negative impact upon both health outcomes and the
      capacity of the state to respond to health issues generally, there has been a
      growing assumption amongst policy makers and practitioners alike that carefully
      formulated health programmes contribute both to social stability and more widely
      to a state- and peace-building agenda. This process risks being co-opted by the
      debates on 'stabilization'--a discourse configured around addressing state
      fragility and often associated with the interventions in Iraq and Afghanistan.
      Consequently, this article explores the emergence of health interventions as
      'strategic tools' linked to the stabilization debate, explores the emergence of
      the 'health as a bridge for peace' (HBP) debate, assesses some of the evidence
      available for HBP and finally focuses on the issues arising from the use of
      militarized health interventions, particularly in Helmand.

PMID- 21721348
TI  - Hyperbaric oxygen: a new adjunctive therapy for surgical-related complications in
      irradiated advanced cancer patients.

PMID- 21721349
TI  - Operative Nd:YAG laser plus postoperative hyperbaric oxygen reduces surgical
      morbidity after radical head and neck cancer surgery and complex reconstruction.
AB  - Complications after radical head and neck cancer surgery in irradiated patients
      are frequent and life-threatening. Hemorrhage, salivary fistulas, wound
      infections that expose the carotid sheath, among others, make these patients
      difficult management challenges in the ICU. We studied the effects of Nd:YAG
      laser surgery plus hyperbaric oxygen (HBO2) therapy on radical head and neck
      resections and complex reconstruction as a means of reducing postoperative
      morbidity and mortality. METHODS: 43 head and neck cancer patients were reviewed.
      Eight (STD) had standard surgery; 35 (YAG:HBO2) had Nd:YAG laser and
      postoperative HBO2. RESULTS: Age, staging, primary tumor site, sex,
      reconstruction procedure and transfusion did not differ between STD and YAG/HBO2.
      All STD and Nd:YAG/HBO2 patients were irradiated, median dosages 5,000 centi-Gray
      (cGy) and 7,000 cGy, respectively (p = 0.073). Median blood loss was 1,000 ml STD
      and 700 ml YAG/HBO2 (p = 0.046). There were no postoperative deaths. Major
      surgical site complications developed in 63% of the STD and 17% of the YAG/HBO2
      patients (p = 0.017). All STD and 62% of YAG/HBO2 cancers recurred within 28
      months of surgery (p = 0.152). Within the STD and YAG/HBO2 groups, 100% and 77%
      of deaths, respectively, were due to cancer. CONCLUSIONS: Combined Nd:YAG laser
      surgery and HBO2 reduces morbidity in radical head and neck cancer surgery.
      Recurrent disease and poor cancer survival remain common in this high-risk
      population.

PMID- 21721350
TI  - Immunohistochemical expression of apoptosis and VEGF expression on random skin
      flaps in rats treated with hyperbaric oxygen and N-acetylcysteine.
AB  - OBJECTIVE: We sought to investigate the role of hyperbaric oxygen (HBO2), N
      acetylcysteine (NAC), and HBO2 plus NAC (HN) on the immunohistochemical
      expression of caspase-3 and the vascular endothelial growing factor (VEGF) on
      random skin flaps of rats (modified McFarlane design). METHODS: Thirty-two male
      Wistar rats were randomly divided into four groups: GS (sham--n = 8); GNAC (N
      acetylcysteine--n = 8); GHBO2 (hyperbaric oxygen--n = 8); and GHN (HBO2 plus NAC-
      n = 8). A rectangular skin flap (2 x 8 cm2) was dissected from the muscular
      dorsal layer, preserving a cranial pedicle. Polyethylene film was placed over the
      muscular layer, and an interrupted 3.0 nylon suture fixed the flap into the
      original place. On the eighth day, full-thickness biopsies (2 x 1 cm2) were
      collected from the proximal, middle and cranial areas of the skin flap, and in a
      site away from the flap labeled the control area. RESULTS: The expression of VEGF
      in the skin layers (epidermis, dermis, subcutaneous muscles) and vessels showed
      no significant difference among the groups. Apoptotic cells were significantly
      increased in the middle area of the flap in all groups. The major increase
      occurred in GS and GNAC. HBO2 significantly decreased cleaved caspase-3-positive
      cell numbers in the skin layers and vessels of the three areas. CONCLUSIONS: HBO2
      showed a protective effect in the ischemic skin flap that was associated with
      reduced expression of apoptosis. GNAC and GHN were not associated with lower
      expression of apoptosis, and poor results were observed in GNAC. The combination
      of NAC and HBO2 did not show better results than using them separately. The
      expression of VEGF in skin layers and vessels did not show a significant
      difference in our modified McFarlane flap model. The results suggest that the
      diffusion of oxygen through the interstitial space was the determining factor for
      the more favorable results of HBO2 in the decrease of apoptosis expression.

PMID- 21721351
TI  - Research report: the effects of hyperbaric oxygen preconditioning on myocardial
      biomarkers of cardioprotection in patients having coronary artery bypass graft
      surgery.
AB  - We have previously conducted and reported on the primary endpoint of a clinical
      study which demonstrated that hyperbaric oxygen (HBO2) preconditioning consisting
      of two 30-minute intervals of 100% oxygen at 2.4 atmospheres absolute (ATA) prior
      to coronary artery bypass graft (CABG) surgery leads to an improvement in left
      ventricular stroke work (LVSW) 24 hours following CABG. In that study, 81
      patients were randomized to treatment with HBO2 (HBO2; n = 41) or routine
      treatment (Control Group; n = 40) prior to surgery. The objective of this
      manuscript is to further report on the result of the exploratory secondary
      endpoints from that study, specifically the effects of HBO2 preconditioning on
      biomarkers of myocardial protection. Intraoperative right atrial biopsies were
      assessed, via an Enzyme Linked ImmunoSorbent Assay (ELISA), for the expression of
      eNOS and HSP72. In this study, no significant differences were observed between
      the groups with respect to the quantity of myocardial eNOS and HSP72. However, in
      the HBO2 Group, following ischemia and reperfusion, the quantities of myocardial
      eNOS and HSP72 were increased. This suggests that HBO2 preconditioning in this
      group of patients may be capable of inducing endogenous cardioprotection
      following ischemic reperfusion injury (IRI).

PMID- 21721352
TI  - Predictions from a mathematical model of decompression compared to Doppler
      scores.
AB  - This paper describes an attempt to calibrate a mathematical model that predicts
      the extent of bubble formation in both the tissue and blood of subjects
      experiencing decompression from a hyperbaric exposure. The model combines an
      inert gas dynamics model for uptake and elimination of inert anesthetic gases
      with a simple model of bubble dynamics in perfused tissues. The calibration has
      been carried out using the model prediction for volume of free gas (bubbles) as
      microl/ml in central venous blood and relating this to Doppler scores recorded at
      the end of hyperbaric exposures. More than 1,000 Doppler scores have been
      compared with the model predictions. Discriminant analysis has been used to
      determine the cut-points between scores below a certain level and all scores at
      or above that level. This allows each prediction from the model to be equated to
      a particular pattern of bubble scores. The predictions from the model are thus
      given a context against the more familiar Doppler scores as a means of evaluating
      decompression stress. It is thus possible to use the mathematical model to
      evaluate decompression stress of a hyperbaric exposure in terms of the predicted
      volume of gas that will form into bubbles and to convert that to a prediction of
      the most likely pattern of Doppler grades which would be recorded from a group of
      subjects experiencing that exposure. This model has been used in assisting
      regulators to set limits to the level decompression risk that should be
      considered acceptable and in assisting those working with decompression
      procedures to design effective modifications.

PMID- 21721353
TI  - Neuropsychological deficits in scuba divers: an exploratory investigation.
AB  - OBJECTIVE: To investigate whether divers with varying levels of experience and
      without a history of reported decompression sickness (DCS) show neuropsychometric
      alterations possibly as a result of so-called repetitive "silent" paradoxical gas
      embolisms. METHODS: Using reaction time as a psychometric measure, 17 experienced
      military divers (ED, logging between 150 and 1,200 diving hours) and eight very
      experienced military divers (VED, logging between 2,800 and 9,800 diving hours)
      with no decompression sickness (DCS) in their medical histories were compared to
      23 healthy controls without any diving history, matched as closely as possible
      with respect to age for the two diving groups. Motor reaction time, decision
      reaction time and error rates were measured during completion of both simple and
      complex reaction time tasks. RESULTS: Compared to their control group, VED showed
      significantly higher motor reaction times on both tasks and significantly higher
      decision reaction times in the complex task. ED were not found to be different
      from their respective controls. No changes in performance quality in terms of
      increased errors were observed in any of the tasks for either diving group.
      CONCLUSIONS: The findings support the proposed possibility that minimal cerebral
      lesions occur after diving even without DCS. Further studies with this highly
      selective population of very experienced divers using more elaborate
      neurocognitive and neuromotor tasks seem warranted.

PMID- 21721354
TI  - Case reports: hyperbaric oxygen therapy for the treatment of cerebral air
      embolism.
AB  - Cerebral air embolism is one of the most deleterious disorders that may affect
      divers, but it is also a possible complication of surgeries and medical
      procedures. We report our experience with iatrogenic cerebral air embolism and
      hyperbaric oxygen treatment.

PMID- 21721355
TI  - Hemoptysis and pneumomediastinum after breath-hold diving in shallow water: a
      case report.
AB  - We report the case of a healthy 21-year-old woman who performed iterative breath
      hold dives in relatively cold water, not exceeding depths of 5 meters but with
      "empty lungs." At the end of a dive, after experiencing an intense involuntary
      diaphragmatic contraction underwater, she presented hemoptysis followed by chest
      pain and cough. Chest radiography and computed tomography were performed 24 hours
      later, confirming the diagnosis of pneumomediastinum. The clinical course was
      benign: However, chest pain and effort dyspnea lasted for a few weeks. The
      pathophysiology of this accident may be explained by a combination of mechanisms
      involved in several clinical entities, namely pulmonary edema of immersion,
      pulmonary barotrauma and spontaneous pneumomediastinum.

PMID- 21721356
TI  - Infectious disease, child care and school.

PMID- 21721357
TI  - Sport participation during adolescence and suicide ideation and attempts.
AB  - BACKGROUND: Most research regarding sport participation and suicide risk found
      protective relationships. However, all studies in this area were based on cross
      sectional designs. OBJECTIVE: To fill a gap in research by exploring associations
      between sport involvement and suicide ideation and attempts (suicidality) based
      on a 5-year longitudinal, population-based study. STUDY GROUP: Participants (n =
      739) completed surveys in middle school and high school. METHODS: Logistic
      regression analysis compared suicidality during high school across four groups:
      youth who participated in sport in both middle and high school, youth who
      participated only in middle school or only in high school, and youth who did not
      participate in sport during adolescence. RESULTS: Compared to non-participants,
      youth involved in sport in both middle and high school had lower odds of suicidal
      ideation during high school. Youth who discontinued sport after middle school had
      higher odds of attempting suicide during high school than non-participants.
      CONCLUSIONS: Remaining involved in sport throughout adolescence can offer mental
      health benefits. Future research should identify mechanisms that account for
      protective relationships between involvement in sport throughout adolescence and
      suicidality, and identify factors that explain deleterious relationships for
      youth who discontinue sport early in adolescence.

PMID- 21721358
TI  - Bullying in middle school: results from a 2008 survey.
AB  - A survey conducted in 2008 among 346 American middle school students in several
      cities determined that 82.7% of respondents found bullying to be a problem of
      some degree, with 46.0% rating it a "medium", "bad", or "very bad" problem. It
      was found that 89% had witnessed an act of bullying and 49.1% said they had been
      the victim of a bully. Boys were significantly more likely than girls to say that
      a victim deserved to be bullied (11.1% vs. 1.3%, p = 0.01), whereas girls were
      significantly more likely than boys to fail to intervene because they did not
      know what to do (30.3% for girls vs. 11.1%, p < 0.01). There was no significant
      difference in this study between boys and girls in terms of being a bully: 43.6%
      admitted they had bullied another (46.2% boys, 41.1% girls, p = 0.34); however,
      girls were significantly more likely than boys to bully by excluding others and
      gossiping about them than by hitting, teasing, or threatening. Cyberbullying,
      surveyed as a distinct entity, had affected 31.1% of respondents directly, with
      similar results from 2006 to 2007 surveys. Of those who found conventional
      bullying a "bad" or "very bad" problem at their schools, numbers fell from 17.3%
      in 2006-2007 vs. 11.3% in 2008.

PMID- 21721359
TI  - Child health and maternal stress: does neighbourhood status matter?
AB  - The purpose of this cross-sectional questionnaire study was to explore
      neighbourhood-level differences in health behaviour, maternal stress and sense of
      coherence, birth weight, child health and behaviour, and children's television
      watching habits. In total, 2006 pairs of Swedish mothers and children, aged
      approximately 20 months, from the general population participated in the study. A
      total of 1923 lived in neighbourhoods of average socioeconomic status in six
      counties, and 83 in a high-status neighbourhood in one of the counties. Data were
      collected in 2002-2003 and 2004-2005 through the Child Health Services. Socio
      demographic confounders were adjusted for in multiple logistic regressions
      (maternal age, country of birth, education, marital status and parity). Compared
      with their counterparts in average neighbourhoods, mothers in the high-status
      neighbourhood were less frequently smokers and had been breastfeeding their
      children more. They felt less stress from social isolation and had a higher sense
      of coherence. All these differences except lower social isolation were non
      significant after adjusting for socio-demographic characteristics. Privileged
      mothers felt more restricted by their parenting tasks (unadjusted comparison),
      and more privileged children were frequent television watchers. Child birth
      weight, health and behaviour were no better in the privileged than in average
      neighbourhoods. This paper adds to previous knowledge by showing that status
      based geographic differences in important parenting and health parameters can be
      non-significant in an equitable society such as Sweden, where all families with
      young children have access to free high-quality health services. Individual
      characteristics could provide better explanations than neighbourhood status.

PMID- 21721360
TI  - Drawing the line in the Edinburgh Postnatal Depression Scale (EPDS): a vital
      decision.
AB  - BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) is widely used in
      early child health care. This study examined the appropriateness of the
      recommended EPDS cut-off score 11/12. METHODS: Two main analyses were performed:
      1. Associations between EPDS scores and maternal health behaviour, stress, life
      events, perceived mother-child interaction quality and child behaviour. 2.
      Screening parameters of the EPDS, i.e., sensitivity, specificity and positive
      predictive value. EPDS scores were available for 438 mothers and maternal
      questionnaires for 361 mothers. RESULTS: Already in the EPDS score intervals 6-8
      and 9-11, there were notable adversities, according to maternal questionnaires,
      in stress, perceived quality of mother-child interaction, perceived child
      difficultness and child problem behaviours. Using maternal questionnaire reports
      about sadness/distress postpartum as standard, the recommended EPDS cut-off score
      11/12 resulted in a very low sensitivity (24%). The cutoff score 6/7 yielded a
      sensitivity of 61%, a specificity of 82% and a positive predictive value of 61%.
      CONCLUSIONS: In terms of both clinical relevance and screening qualities, an EPDS
      cut-off score lower than 11/12 seems recommendable.

PMID- 21721361
TI  - Alcohol use, related problems and psychological health in college students.
AB  - This study examined the prevalence of alcohol use, alcohol-related problems,
      psychological distress, anxiety and depression mood and the relationship between
      these variables in a sample of 534 college students in the USA. In college men,
      91% were current alcohol users (those who use alcohol at least once a month) and
      in college women 80% were current alcohol users (p < 0.01). Current users were
      further divided into two groups, moderate and heavy, considering the amount and
      frequency of alcohol use. Beer was more popular among moderate users than heavy
      users in both sexes. Over 90% of both moderate and heavy users in both men and
      women had used hard liquor in the 30-day period preceding the survey. College men
      had more alcohol-related problems than did college women. Blackouts, getting into
      fights and not being able to meet school responsibilities were the common alcohol
      related adverse outcomes reported by the participants. No associations were found
      between alcohol use and distress and between alcohol use and depressive mood.
      Mean values of the anxiety scores, however, were higher in moderate users in the
      male sample compared to that of the female sample. The findings have implications
      for theories of alcohol-related psychological health in college students.

PMID- 21721362
TI  - Cross-cultural validity of the scale for interpersonal behavior.
AB  - The Scale for Interpersonal Behavior (SIB) is a 50-item multidimensional measure
      of difficulty and distress in assertiveness. The SIB assesses negative assertion,
      expression of and dealing with personal limitations, initiating assertiveness and
      positive assertion. The SIB was originally developed in the Netherlands. The
      present study attempted to replicate the original factors with an Italian student
      sample (n = 995). The four distress and four performance factors were replicable
      across two methods of analysis (the multiple group method of confirmatory
      analysis and Tucker's coefficient of congruence (phi). The corresponding scales
      were internally consistent and showed predicted patterns of correlations with a
      measure of self-efficacy. Sex and age differences in assertiveness were generally
      negligible. Italian students had higher positive assertion-performance scores
      than the Dutch and comparable scores on other performance scales; by contrast,
      the Italian subjects had significantly higher scores on all SIB distress scales
      than their Dutch equivalents. This was ascribed to the stronger pressure on
      people in Italian society to behave assertively (Hofstede's National Masculinity
      score = 70) as opposed to the Dutch society (National Masculinity score = 14).

PMID- 21721363
TI  - Level of training of nursing staff and the autonomy given to psychiatric
      inpatients: a multicenter study.
AB  - This research examines the influence of the level of professional training of the
      caretaking staff in psychiatric wards, the type of wards in which a patient is
      treated and the patient's age compared with the level of limitation put on
      patient autonomy. Detailed questionnaires were administered to 296 nurses from
      five mental health centers who met inclusion criteria for the study. The level of
      autonomy restriction was measured using six representative cases from fieldwork
      of the interviewees. These cases were analyzed by the authors based on Collopy's
      theory, by categorizing the data according to the six polarities of autonomy
      presented in his work. Our findings suggest a positive correlation between the
      level of professional training of the nursing staff, patient's age and the level
      of autonomy given. Our findings did not show a significant relationship between
      the type of ward and level of autonomy, although there could be a tendency for
      higher autonomy within closed wards.

PMID- 21721364
TI  - Correlates of identity statuses among Chinese adolescents in Hong Kong.
AB  - This study investigates correlates of Hong Kong Chinese adolescents' identity
      statuses with (i) parental and school contexts and (ii) major psychosocial
      developmental outcomes. Data were collected from 1260 Secondary 2-4 (equivalent
      to Grades 8-10 in the US school system) students through a questionnaire survey.
      Results of hierarchical regression analysis indicated that parental attributes of
      acceptance, values and goals, and psychological control, and school contextual
      factor of task orientations predicted identity achievement, whereas parents'
      acceptance, psychological and firm control, and teacher's support predicted
      identity foreclosure. Regarding the impact on psychosocial development, another
      series of regression analyses revealed that (i) identity achievement predicted
      low depression, high self-esteem, and high self-efficacy; (ii) moratorium
      predicted low self-esteem; and (iii) foreclosure predicted high self-efficacy.
      Overall, the findings shed light on adolescent identity development in Hong Kong,
      facilitating discussions on identity-related issues.

PMID- 21721365
TI  - A pilot study: pain, fatigue and stress in maternal relatives of adolescent
      female psychiatric inpatients assessed for juvenile primary fibromyalgia
      syndrome.
AB  - BACKGROUND: This study was designed to assess the presence of pain and impaired
      functioning in the maternal relatives of adolescent females in an inpatient
      adolescent psychiatric population. We compared the relatives of adolescents who
      met the criteria for juvenile primary fibromyalgia syndrome (JPFS) to relatives
      of adolescents who did not meet the criteria for JPFS. METHODS: A total of 55
      biological maternal relatives of adolescent females admitted to a psychiatric
      unit were recruited to participate in the study. Participants completed four self
      administered questionnaires: Multidimensional Fatigue Inventory, Fibromyalgia
      Impact Questionnaire, Medical Outcomes Survey (SF36v2), and the EPIFUND Health
      Survey. RESULTS: The maternal relatives of adolescents who met the criteria for
      JPFS did not score higher than the maternal relatives of adolescents who did not
      meet the criteria for JPFS. However, all maternal relatives consistently scored
      higher on self-reported measures of pain, impaired functioning, fatigue, and
      fibromyalgia symptoms than the average patient diagnosed with fibromyalgia or a
      chronic pain syndrome. CONCLUSION: Mood disorders and pain disorders share
      genetic risk factors and vulnerability. Future research is needed to further
      delineate other factors impacting the maternal caregivers' functioning. These
      could include stress associated with an adolescent child with psychiatric issues
      severe enough to warrant hospitalization.

PMID- 21721366
TI  - Text messaging: one step forward for phone companies, one leap backward for
      adolescence.
AB  - The increasing popularity of text messaging has made this mode of communication
      the preferred interaction portal for teens. Virtually every teenager has a cell
      phone with an unlimited text messaging plan. Text messaging easily facilitates
      communication between individuals without much interruption into daily life.
      After administering a survey to ten early adolescents and ten late adolescents,
      the effects of this technology are manifested across many developmental
      characteristics. Communication, responsibility, and relationships all seem to be
      negatively influenced by the use of text messaging. This pattern is seen in both
      early and late adolescent groups. Developmentally, different characteristic
      features categorize early and late adolescence, yet it seems the use of text
      messaging is propelling early adolescence forward by removing the consequences of
      awkward face-to-face interactions. This early onset of late adolescence results
      in having very young teens, 12 and 13 year olds, showing increased interest in
      romantic relationships and sexual exploration. The anxiety and uneasiness felt by
      early teens about speaking with others has led to deficits in the ability to
      communicate in social settings, which could prove troublesome later. This study
      looks at only a few developmental issues associated with text messaging use among
      teens. It would be relevant and appropriate to study other ways that text
      messaging affects our youth in addition to exploring the more long-term effects
      of using this technology.

PMID- 21721367
TI  - Iron deficiency anemia presenting as pancytopenia in an adolescent girl.
AB  - Iron deficiency anemia is commonly associated with thrombocytosis and normal
      leukocyte count. Thrombocytopenia has occasionally been reported in iron
      deficiency anemia, but pancytopenia is very rare. We present a case of a young
      female who presented with iron deficiency anemia associated with pancytopenia
      that improved with iron replenishment after initial deterioration, the mechanism
      of which is also discussed in this case report. This case illustrates two
      uncommon associations of a very common disease: severe iron deficiency can be
      associated with pancytopenia and can be initially worsened by iron replacement
      despite normal serum B12 and folic acid levels.

PMID- 21721368
TI  - Menstrual bleeding patterns in adolescents using etonogestrel (ENG) implant.
AB  - BACKGROUND: Etonogestrel (ENG) implant is an effective method of contraception.
      The implant is designed to provide contraceptive efficacy for 3 years with a
      relatively quick return of fertility upon its removal. Menstrual irregularities
      are not uncommon on long-acting progestins and can often be the factor for
      discontinuation or removal. A retrospective chart analysis was done on 58
      patients who chose to be on the ENG implant. Age ranged from 12 to 24 years. The
      cycle ranged from 1 to 17 months. The mean length of use of the implant was 10.9
      months. Over the 20-month period, 13 ENG implants were removed because of
      menstrual bleeding problems. METHOD: We conducted a chart review of the
      adolescent patients who received the ENG implant in our adolescent clinic. An
      analysis was done based on symptoms experienced by patients who were on the ENG
      implant and their management, which in some cases resulted in its removal.
      SETTING: The data is presented on adolescent and young adult patients who receive
      their reproductive care in the Adolescent Medicine Clinic at the University of
      Kentucky, Lexington, KY, USA. CONCLUSIONS: ENG implant when used correctly and as
      indicated is extremely effective in providing contraception for up to 3 years.
      However, menstrual irregularities can be very troublesome and often a reason for
      its removal. In our experience, 22.4% (13 out of the 58 subjects) had menstrual
      problems post-insertion that led to its removal. It is crucial for a clinician to
      inform and be informed about such side effects.

PMID- 21721369
TI  - Residential care centers for persons with intellectual disability in Israel.
      Trends in the number of children 1999-2008.
AB  - In 1998, a questionnaire was developed by the Health Services, Office of the
      Medical Director at the Ministry of Social Affairs and Social Services. This
      questionnaire was aimed to assess, on a yearly basis, the health of the residents
      with intellectual disability and the services provided to them by specific
      residential care centers within Israel. The present study was conducted to
      examine trends in the number of children with intellectual disability in
      residential care centers in Israel during 1999-2008. We demonstrated a clear
      downward trend with regard to the percent of children living in residential care
      facilities, from 18.1% of the total population in 1999 to 12.8% in 2008.

PMID- 21721370
TI  - Enhanced diagnosis of pollen allergy using specific immunoglobulin E
      determination to detect major allergens and panallergens.
AB  - BACKGROUND: Pollen is one of the main causes of allergic sensitization. It is not
      easy to make an etiological diagnosis of pollen-allergic patients because of the
      wide variety of sensitizing pollens, association with food allergy, and
      increasing incidence of polysensitization, which may result from the presence of
      allergens that are common to different species, as is the case of panallergens.
      OBJECTIVE: To compare the results of skin prick tests (SPT) using whole pollen
      extract with specific immunoglobulin (Ig) E determination for several allergens
      (purified panallergens included) in the diagnosis of polysensitized pollen
      allergic patients. METHODS: The study sample comprised 179 pollen-sensitized
      patients who underwent SPT with pollen extract and allergen-specific IgE
      determination against different allergens. RESULTS: The level of concordance
      between the traditional diagnostic test (SPT) and IgE determination was low,
      especially in patients sensitized to the panallergens profilin and polcalcin. In
      the case of SPT, the results demonstrated that patients who are sensitized to
      either of these panallergens present a significantly higher number of positive
      results than patients who are not. However, IgE determination revealed that while
      patients sensitized to polcalcins are sensitized to allergens from a higher
      number of pollens than the rest of the sample, this is not the case in patients
      sensitized to profilins. On the other hand, sensitization to profilin or lipid
      transfer proteins was clearly associated with food allergy. CONCLUSIONS:
      Sensitization to panallergens could be a confounding factor in the diagnosis of
      polysensitized pollen-allergic patients as well as a marker for food allergy.
      However, more studies are required to further investigate the role of these
      molecules.

PMID- 21721371
TI  - Serum tryptase level is a better predictor of systemic side effects than
      prostaglandin D2 metabolites during venom immunotherapy in children.
AB  - OBJECTIVES: We performed a prospective study to analyze mast cell mediators as
      predictors of systemic adverse reactions during rush venom-specific immunotherapy
      (VIT) in children. PATIENTS AND METHODS: Nineteen children aged 5-17 years
      received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP,
      Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and
      urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas
      chromatography mass spectrometry before and after the rush protocol. RESULTS:
      Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and
      low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse
      reactions during VIT. Baseline serum tryptase was lowest in children who had a
      Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a
      Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis
      of variance confirmed that, in children who developed systemic adverse reactions
      during VIT, serum tryptase was higher both before and after desensitization and
      increased significantly following the procedure. Analysis of PGD2 metabolites in
      the prediction of systemic adverse reactions during VIT was inadequate
      (sensitivity 67% and specificity 0.53%), whilst prediction based on serum
      tryptase was accurate. CONCLUSIONS: In children with severe systemic adverse
      reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should
      be a standard procedure. Children with Apis mellifera venom allergy and baseline
      tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup.
      Lower baseline values of plasma and urinary PGD2 metabolite concentration in
      patients with systemic adverse reaction during VIT suggest that prostaglandin
      catabolism is altered.

PMID- 21721372
TI  - Prevalence, burden, and risk factors of atopic eczema in schoolchildren aged 10
      11 years: a national multicenter study.
AB  - BACKGROUND: Little is known about the epidemiology of atopic eczema (AE), and
      studies from the Mediterranean region and the Middle East are limited. OBJECTIVE:
      We investigated the frequency, burden, and risk factors of AE in a developing
      country. METHODS: The International Study of Asthma and Allergies in Childhood
      Phase II questionnaire was used to survey a representative sample of 10 to 11
      year-old children in Turkey. Children were examined by allergists, and parents
      completed standardized questionnaires. RESULTS: Among 6755 children, the
      prevalence of having eczema during one's lifetime or currently was 17.1% and
      8.1%, respectively. The prevalence of visits to the doctor, nocturnal awakening,
      school absenteeism, and drug usage was 36.3%, 56%, 9.7%, and 28.7%, respectively.
      Associated factors were current rhinoconjunctivitis (odds ratio [OR], 2.53; 95%
      confidence interval [CI], 1.99-3.21), current wheezing (OR, 2.10; 95% CI, 1.58
      2.79), family history of allergic disease (OR, 1.62; 95% CI, 1.21-2.18), low
      birth weight (OR, 1.79; 95% CI, 1.08-2.94), and exposure to animals in the first
      year of life (OR, 1.47; 95% CI, 1.06-2.03). CONCLUSIONS: In a developing
      Mediterranean country, the prevalence of AE is comparable to that of developed
      countries in the same region and lower than that observed in developed countries
      elsewhere. The course of the disease and risk factors of AE probably differ in
      developing countries.

PMID- 21721373
TI  - Prevalence of sensitization to lipid transfer proteins and profilins in a
      population of 430 patients in the south of Madrid.
AB  - BACKGROUND: Lipid transfer proteins (LTPs) and profilins are the most important
      panallergens in the management of patients who are allergic to pollen and plant
      food in our area. LTPs are highly stable proteins that can induce systemic
      symptoms after ingestion. Profilins are labile proteins that are present in
      pollens and vegetables. Considered markers of several types of pollen
      sensitization, they are responsible for cross-reactivity between pollens and
      vegetables. The objective of this study was to assess the frequency of
      sensitization to LTP and profilin using skin prick tests (SPTs) in patients
      referred to our allergy unit for any complaint (not only pollen and plant food
      allergy). METHODS: The study sample comprised 430 consecutive patients who were
      evaluated using their medical history and SPTs with pollen, date palm profilin,
      and peach extract enriched in Pru p 3 (30 g/mL) as an LTP marker. RESULTS: We
      found that 52 (12.1%) patients were sensitized to profilin and 53 (12.3%) to LTP.
      Pollen allergy was diagnosed in 53% and plant food allergy in 11%. In the LTP
      sensitized group and the profilin-sensitized group, 37.7% and 34.6% of the
      patients had plant food allergy, respectively. Thirty-three patients (62.3%) were
      sensitized to LTP but had no symptoms after eating vegetables. CONCLUSIONS: To
      the best of our knowledge, this is the first study to analyze the real rate of
      sensitization to profilin and LTP in a population sensitized to allergens other
      than pollens and plant foods. Twelve percent of patients were sensitized to both
      profilin and LTP. A large proportion of LTP-sensitized patients had no symptoms
      at the time of the study.

PMID- 21721374
TI  - Adaptation and validation of the Spanish version of the Quality Of Life in Latex
      Allergy questionnaire (QOLLA).
AB  - OBJECTIVE: The aim of the present study was to translate into Spanish and
      transculturally adapt the Quality of Life in Latex Allergy questionnaire (QOLLA)
      in order to provide a validated instrument for use in research and daily
      practice. METHODS: Patients diagnosed with latex allergy were invited to
      participate in an observational prospective multicenter study to validate the
      Spanish version of the QOLLA following the recommendations of the World Health
      Organization. The study included 3 phases--feasibility, reliability, and cross
      sectional validation-and was approved by the Ethics Committee of Hospital Ramon y
      Cajal. RESULTS: Mean time to complete the questionnaire was 4.7 minutes. The
      maximum score was 28 (mean, 7.7; median, 4).The SF-12 score ranged from 25.8 to
      51.6 in the physical domain and from 20.8 to 61.5 in the mental domain. Internal
      consistency was excellent (Cronbach alpha, 0.9348). The kappa index fluctuated
      between 0.40 and 0.93. A kappa of 0.84 was obtained for the global score in 5
      categories. Sixty patients were included to evaluate construct validity. Mean age
      was 39 years and 49 patients were women (80%). The global score ranged between 0
      and 30 (mean, 11.69; median, 11). Spearman correlation coefficients between the
      QOLLA and a visual analog scale and the SF-12 physical, mental, and severity
      scales according to the researcher were--0.47, 0.37, 0.29, and 0.54,
      respectively. CONCLUSION: The QOLLA is a feasible, valid, and reliable instrument
      for the measurement of disease-specific quality of life in adult patients
      diagnosed with latex allergy. It could play an important role in determining
      suitable treatment for latex-allergy.

PMID- 21721375
TI  - Asthma in obese women: outcomes and factors involved.
AB  - OBJECTIVE: It has been shown that the prevalence of asthma in obese people has
      increased in recent years. The aim of this study was to evaluate factors involved
      in the relationship between asthma and obesity in women, METHODS: We evaluated
      serum leptin levels, fractional exhaled nitric oxide (FE(N0), asthma control
      (using theAsthma Control Test [ACT]), and presence of atopy in 41 obese women
      with asthma and 40 non-obese women with asthma. We also compared the relationship
      between body mass index (BMI) and these parameters between the 2 groups. RESULTS:
      Serum leptin levels were significantly higher in obese asthmatics than in
      nonobese asthmatics (P < .05). In the obese group, leptin levels were positively
      correlated with FE(O) levels (r = 0.439, P = .004). Uncontrolled asthma (ACT
      score <20) was detected in 61% of women in the obese group compared to just 38%
      of those in the nonobese group (P = -.035). In atopic patients, total
      immunoglobulin E levels were positively correlated with leptin levels (r = 0.329,
      P = .038). When the 81 women were classified according to asthma control, high
      BMI was found to be the only significant factor that contributed to poor asthma
      control. CONCLUSION: We have shown that serum leptin levels might have a role in
      poor asthma control in obese patients, and can conclude that obesity is an
      important factor in uncontrolled asthma.

PMID- 21721376
TI  - Naturally occurring regulatory T cells and interleukins 10 and 12 in the
      pathogenesis of idiopathic warm autoimmune hemolytic anemia.
AB  - OBJECTIVES: Naturally occurring regulatory T cells (nTregs) play an important
      role in immunologic tolerance and control immune-mediated pathology in murine
      models of autoimmune hemolytic anemia. Our aim was to measure nTregs and levels
      of interleukin (IL) 10 and IL-12 in peripheral blood mononuclear cell (PBMC)
      cultures from patients with idiopathic warm autoimmune hemolytic anemia (wAIHA)
      in an attempt to unravel some of the mysteries behind the pathogenesis of this
      autoimmune disorder. METHODS: Twenty-seven patients with idiopathic wAIHA and 15
      age- and sex-matched controls underwent flow cytometric analysis of CD4+ CD25high
      FoxP3+ T cells (nTregs) and analysis by enzyme-linked immunosorbent assay of IL
      10 and IL-12 in the supernatants of basal and lipopolysaccharide (LPS)-stimulated
      PBMC cultures. RESULTS: The mean (SD) percentage of circulating CD4+ nTregs in
      peripheral blood was significantly lower in patients (4.63% [1.0%]) than in
      controls (9.76% (0.78%])(P<.001). PBMCs from patients had significantly higher
      basal levels of Il-10 and IL-12, with a dramatic reduction in responsiveness to
      LPS in vitro compared to controls. There was a significantly negative correlation
      between the percentage of nTregs and reticulocyte count (RC), basal IL-10, and
      LPS-stimulated IL-10, and a significantly positive correlation with haptoglobin
      (Hp) (P<.05). Basal IL-10 and LPS-stimulated IL-10 were positively correlated
      with RC (P < .001 in both cases) and negatively correlated with Hp (P<.01 and
      P<.05, respectively). CONCLUSION: Our study indicates that a reduced percentage
      of nTregs and IL-10/IL-12 imbalance may play an essential role in the onset
      and/or maintenance of this AIHA.

PMID- 21721377
TI  - Contact angioedema and rhinoconjunctivitis caused by Dendrobaena species and
      Sarcophaga carnaria used as fishing bait.
AB  - The flesh fly Sarcophaga carnaria is commonly used as fishing bait.
      Immunoglobulin (Ig) E-mediated reactions caused by the handling of this bait have
      been reported. The earthworm Dendrobaena species is increasingly being used as
      fishing bait but there have been no reported cases of allergy to this species to
      date. We studied a 26-year-old amateur angler who presented rhinoconjunctivitis,
      urticaria, and angioedema on handling S carnaria. He started to use Dendrobaena
      species instead but developed the same symptoms. The aim of this study was to
      identify the allergens involved in the patient's clinical reactions. The study
      was performed using immunoglobulin (Ig) E immunoblotting and immunoblotting
      inhibition assays.The patient's serum detected allergens from Dendrobaena species
      (of an apparent molecular weight of approximately 150, 60, 37, 24, 21 and 19 kDa)
      and S. carnaria (approximately 70 kDa and a smear ranging from 50 to 40 kDa). The
      patient was diagnosed with allergy to both Dendrobaena species and 5 carnaria.
      This is the first case describing Dendrobaena species as an allergic agent.

PMID- 21721378
TI  - Chronic granulomatous disease presenting with hypogammaglobulinemia.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder caused
      by inherited defects in the nicotinamide adenine dinucleotide phosphate oxidase
      complex. The neutrophils of patient with CGD can ingest bacteria normally, but
      the oxidative processes that lead to superoxide anion formation, hydrogen
      peroxide production, nonoxidative pathway activation, and bacterial killing are
      impaired. Serious infections result from microorganisms that produce catalase.
      Immunoglobulin levels of patients with CGD are usually normal or elevated. We
      describe a patient with CGD associated with hypogammaglobulinemia, an unusual co
      occurrence.

PMID- 21721379
TI  - Cernunnos deficiency: a case report.
AB  - B cell-negative severe combined immunodeficiency (SCID) is caused by molecules
      involved in the variable (diversity) joining (V[D]J) recombination process. Four
      genes involved in the nonhomologous end joining pathway--Artemis, DNA-PKcs, DNA
      ligase 4, and Cernunnos--are involved in B cell-negative radiosensitive SCID.
      Deficiencies in DNA ligase 4 and the recently described Cernunnos gene result in
      microcephaly, growth retardation, and typical bird-like facies. Lymphopenia and
      hypogammaglobulinemia with normal or elevated immunoglobulin (Ig) M levels
      indicate a defect in V(D)J recombination. We present a case with recurrent
      postnatal pulmonary infections leading to chronic lung disease, disseminated
      molluscum contagiosum, lymphopenia, low IgG, IgA and normal IgM levels. Our
      patient had phenotypic features such as microcephaly and severe growth
      retardation. Clinical presentation in patients with the B cell-negative subtype
      ranges from SCID to atypical combined immunodeficiency, occasionally associated
      with autoimmune manifestations and cytomegalovirus infection. Our patient
      survived beyond infancy with combined immunodeficiency and no autoimmune
      manifestations.

PMID- 21721380
TI  - Anaphylaxis to dimenhydrinate caused by the theophylline component.

PMID- 21721381
TI  - Allergy to crayfish.

PMID- 21721382
TI  - Successful rapid rituximab desensitization for hypersensitivity reactions to
      monoclonal antibodies in a patient with rheumatoid arthritis: a remarkable
      option.

PMID- 21721383
TI  - Anaphylactic shock caused by antihistamines.

PMID- 21721384
TI  - Measurements of fractional exhaled nitric oxide with 2 portable electrochemical
      sensors: a comparative study.

PMID- 21721385
TI  - Hypersensitivity to pollen panallergens (profilin and polcalcin) detected in
      vitro and in vivo: a comparative analysis.

PMID- 21721386
TI  - Immediate type 1 hypersensitivity to apomorphine: a case report.

PMID- 21721387
TI  - Identification of allergens in chicken meat allergy.

PMID- 21721388
TI  - Effect of alcohol consumption and cessation on serum total immunoglobulin E
      concentrations.

PMID- 21721389
TI  - Uterine contractions are known side effects of venom immunotherapy.

PMID- 21721391
TI  - Medication safety: an essential nursing role.

PMID- 21721392
TI  - Clinical consultation: nonpharmacologic management of agitated behaviors after
      traumatic brain injury.

PMID- 21721393
TI  - Aphasia Bill of Rights.

PMID- 21721394
TI  - Changes in functional independence measure ratings associated with a safe patient
      handling and movement program.
AB  - Safe patient handling and movement (SPHM) programs are effective in reducing
      healthcare worker injuries. However, the perception among rehabilitation
      personnel that SPHM equipment promotes patient dependence and adversely affects
      functional outcomes is one barrier to implementing successful programs. This
      barrier is particularly evident in acute inpatient rehabilitation facilities,
      where functional independence is the primary goal. The purpose of this
      retrospective cohort study was to evaluate this perception. Functional
      Independence Measure (FIM) ratings were collected from 94 patients with a
      diagnosis of stroke. Forty-seven patients were admitted 1 year prior to
      implementation of the SPHM program (Group 1), and 47 were admitted to the
      facility over a period of 1 year (Group 2) 18 months after program
      implementation. Group 2 obtained equal or better discharge mobility FIM ratings
      than Group 1, who received care without the SPHM equipment. This study suggests
      that SPHM programs do not impede functional outcomes in stroke patients.

PMID- 21721395
TI  - Wheelchair positioning and breathing in children with cerebral palsy: study
      methods and lessons learned.
AB  - In children with cerebral palsy (CP), poor trunk control can lead to spinal
      deformity, pulmonary compromise (Canet, Praud, & Bureau, 1998), and increased
      health risks and costs of long-term care (Braddock, 2002). Evidence links posture
      and pulmonary function, but the influence of wheelchair components on pulmonary
      function is unknown. This article reports on a study evaluating pulmonary
      measurement in wheelchairs and how it affected children with CP. The objectives
      of the study were to (a) describe recruitment and retention of school-aged
      children with CP and (b) discuss participants'response to the protocol. Using a
      wheelchair simulator, participants experienced five seating parameters while
      pulmonary mechanics measures were recorded. A process log captured participant
      recruitment and retention challenges and response to the protocol. Recruitment
      was challenging; retention was 50%. The protocol was feasible for 50% of
      participants, none of whom could participate in conventional pulmonary function
      testing. Among the study's participants, facemask and seating simulator
      acceptability were 75%, improving with participants'increased verbal
      communication abilities (verbal children tolerated the procedure best). The
      facemask was vulnerable to tilt; 75% of participants experienced fatigue.

PMID- 21721396
TI  - Spinal cord injury/disorder teleconsultation outcome study.
AB  - The purpose of this study was to compare the costs of providing specialty wound
      care to spinal cord injury/disorder (SCI/D) veterans by teleconsultation and
      traditional care. A retrospective design was used to conduct this descriptive,
      correlational study. A convenience sample of 76 SCI/D veterans (2 women, 74 men)
      met inclusion criteria from a possible 123 subjects. Variables were compared
      between groups using nonparametric methods (Wilcoxon rank sums and chi-square).
      There was no significant difference in inpatient admissions or inpatient bed days
      of care between the two groups. The teleconsultation group had more outpatient
      encounters (medians 12 vs. 4, p = .007; Wilcoxon statistic = 412.5) and longer
      inpatient stays (medians 81 vs. 19 days/admission, p = .05; Wilcoxon statistic =
      227.0) compared to the traditional care group. There was no significant
      difference in inpatient cost between the two groups; however, the
      teleconsultation group had a significantly higher median cost per outpatient
      encounter ($440 vs. $141, p <.0001; Wilcoxon statistic = 469.0). Although this
      study only looked at costs directly associated with wound management, continued
      research exploring the use of teleconsultation in other areas of SCI/D specialty
      is needed to enhance its application.

PMID- 21721397
TI  - The effectiveness of nurse-led, home-based pulmonary rehabilitation in patients
      with COPD in Turkey.
AB  - The goal of this study was to determine the effectiveness of nurse-led, home
      based pulmonary rehabilitation in patients with stage 3 or 4 chronic obstructive
      pulmonary disease (COPD), according to the Global Initiative for COPD (GOLD)
      staging system. The study consisted of 32 patients--a nurse-led, home-based
      pulmonary rehabilitation group (16) and a control group (16). In the
      rehabilitation program, patients received education about their diseases and
      performed breathing exercises and lower- and upper-extremity aerobic exercises at
      their homes during the 3-month period of the study. There was meaningful
      improvement in the rehabilitation group in terms of pulmonary function tests
      (FEV1 % predicted value), artery blood gases (PaCO2), quality of life, dyspnea,
      and functional capacity. On the other hand, no meaningful change was observed in
      the control group. The study showed that the nurse-led, home-based pulmonary
      rehabilitation program had positive effects on the patients with COPD.

PMID- 21721398
TI  - Cultural cues: review of qualitative evidence of patient-centered care in
      patients with nonmalignant chronic pain.
AB  - The purpose of this paper was to examine published qualitative studies that
      explored the beliefs, values, and behaviors of patients with nonmalignant chronic
      pain during their interactions with the healthcare system. The findings were used
      as "cultural cues" to create patient-centered care. A literature review of
      primary qualitative studies that focused on beliefs, values, or behaviors of
      patients with chronic nonmalignant pain in the formal healthcare setting was
      conducted. CINAHL, Medline, Pubmed, PsychInfo, Sociology Abstracts, Cochrane
      Library Database, Proquest Dissertation and Thesis, and EmBase served as the
      database for the research. The findings from the studies fell into two
      categories: beliefs and expectations about appropriate treatment and the
      behaviors patients may exhibit if they perceive they are not receiving
      appropriate treatment. Qualitative findings showed that the beliefs, values, and
      behaviors of patients with nonmalignant chronic pain exhibited during their
      interactions with the healthcare system created a set of "cultural cues" for
      providers.

PMID- 21721399
TI  - Gestational length in Carthusian broodmares: effects of breeding season, foal
      gender, age of mare, year of parturition, parity and sire.
AB  - The length of gestation in Carthusian broodmares was calculated on the basis of
      339 spontaneous full-term deliveries taking place in the 8-year period 1998-2005
      from 158 broodmares and 29 stallions in a major farm of Spanish horses of
      Carthusian strain in southern Spain. Ultrasonography was used to determine
      follicular dehiscence, 1st day of pregnancy and to confirm conception in mares.
      Mean GL was 332.4 +/- 12.1 days, and a normal interval of 297-358 days was
      established for this breed. GL records were grouped on the basis of foal sex
      (colts or fillies), mating month (between November and January; February and
      April; May and July), age of the mare (4 to 7 years; 8 to 12 years; 13 to 17
      years), breeding year, stallion and parity (primiparous vs. multiparous). GLs
      were 12.9 days shorter in mares mated between May and July than those mated
      between November and January and 15.3 days in mares mated between February and
      April (p < 0.001). Mares aged between 8-12 years had 5.3 days shorter GLs than
      those aged between 13-17 years (p < 0.05). Pregnancy was significantly 5.7 days
      longer when the mare gave birth to colts than fillies (p < 0.05). GL was 14.5
      days longer in primiparous than in multiparous mares ( p < 0.001). No statistical
      differences in GL were found between the studied years. This study shows the
      influence of certain stallion on GL.

PMID- 21721400
TI  - The influence of botulinum toxin type A (BTX) on the immunohistochemical
      characteristics of noradrenergic and cholinergic nerve fibers supplying the
      porcine urinary bladder wall.
AB  - Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence
      the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX
      has been used as an effective drug in experimental therapies of a range of
      neurogenic bladder disorders. However, there is no detailed information dealing
      with the influence of BTX on the morphological and chemical properties of nerve
      fibres supplying the urinary bladder wall. Therefore, the present study
      investigated, using double-labeling immunohistochemistry, the distribution,
      relative frequency and chemical coding of cholinergic and noradrenergic nerve
      fibers supplying the wall of the urinary bladder in normal female pigs (n = 6)
      and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected
      with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in
      the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher
      while the number of cholinergic (VAChT-positive) nerve terminals was lower than
      that found in the control animals. Moreover, the injections of BTX resulted in
      some changes dealing with the chemical coding of the adrenergic nerve fibers. In
      contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or
      DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres
      distributed in the urothelium and submucosa expressed immunoreactivity to CGRP.
      The results obtained suggest that the therapeutic effects of BTX on the urinary
      bladder might be dependent on changes in the distribution and chemical coding of
      nerve fibers supplying this organ.

PMID- 21721401
TI  - The effects of florfenicol on lymphocyte subsets and humoral immune response in
      mice.
AB  - Florfenicol is a broad-spectrum bacteriostatic antibiotic used in domestic
      animals. The aim of the study was to determine the effect of florfenicol on the
      total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes and
      the percentage and the absolute number of T cell subsets (CD4+CD8+, CD4-CD8-,
      CD4+, CD8+) in the thymus and T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in
      the peripheral lymphatic organs in non-immunized mice and humoral immune response
      in sheep red blood cells (SRBC)-immunized mice. Florfenicol was administered
      orally at a dose of 30 mg/kg six times at 24 h intervals to non-immunized mice
      and four or seven times at 24 h intervals to SRBC-immunized mice. SRBC was
      injected 2 hours prior to the first dose of the drug. Florfenicol increased the
      percentage of CD4CD8- thymocytes and the absolute number of CD4+ and CD8+
      thymocytes on day 7. The increased percentage and absolute number of CD3+, CD4+
      and CD8+ lymphocytes in mesenteric lymph nodes and decreased percentage of
      lymphocytes B were also observed 24 hours from the last administration of
      florfenicol. Florfenicol administered after SRBC immunization reduced the number
      of plaque forming cells (PFC) and the production of anti-SRBC antibodies on days
      4 and 7 after priming.

PMID- 21721402
TI  - Immunohistochemical properties of motoneurons supplying the trapezius muscle in
      the rat.
AB  - Combined retrograde tracing (using fluorescent tracer Fast blue) and double
      labelling immunofluorescence were used to study the distribution and
      immunohistochemical characteristics of neurons projecting to the trapezius muscle
      in mature male rats (n = 9). As revealed by retrograde tracing, Fast blue
      positive (FB+) neurons were located within the ambiguous nucleus and accessory
      nucleus of the grey matter of the spinal cord. Immunohistochemistry revealed that
      nearly all the neurons were cholinergic in nature [choline acetyltransferase
      (ChAT)-positive]. Retrogradely labelled neurons displayed also immunoreactivities
      to calcitonin gene-related peptide (CGRP; approximately 60% of FB+ neurons),
      nitric oxide synthase (NOS; 50%), substance P (SP; 35%), Leu5-Enkephalin (LEnk;
      10%) and vasoactive intestinal polypeptide (VIP; 5%). The analysis of double
      stained tissue sections revealed that all CGRP-, VIP- and LEnk-immunoreactive FB+
      perikarya were simultaneously ChAT-positive. The vast majority of the neurons
      expressing SP- or NOS-immunoreactivity were also cholinergic in nature; however,
      solitary somata were ChAT-negative. FB+ perikarya were surrounded by numerous
      varicose nerve fibres (often forming basket-like structures) immunoreactive to
      LEnk or SP. They were also associated with some CGRP-, NOS- and neuropeptide Y
      positive nerve terminals.

PMID- 21721403
TI  - Occurrence of virulence genes among Campylobacter jejuni and Campylobacter coli
      isolates from domestic animals and children.
AB  - The presence of the flaA, cadF, cdtB and iam genes of Campylobacter spp. was
      determined with the PCR method. The materials to investigate were 56 C. jejuni
      and 23 C. coli strains isolated from clinical samples (children and domestic
      animals). It was found that all of the Campylobacter spp. isolates from children
      with diarrhoea and domestic animals had cadF gene, responsible for adherence. The
      flaA gene was present in all Campylobacter spp. isolates derived from children
      and cats. Occurrence of flaA gene was confirmed in 100% of C. jejuni strains
      obtained from dogs. The high prevalence of the cdtB gene associated with toxin
      production was observed in this study (100%-Campylobacter spp. isolates obtained
      from dogs and cats, 97.9%-Campylobacter spp. isolates from children). The
      isolates showed a wide variation for the presence of iam gene. The lowest
      prevalence (23.5%) was detected in Campylobacter spp. obtained from dogs. The
      highest rates of iam detection (91.6%) were revealed in C. coli isolates from
      children.

PMID- 21721404
TI  - Antibiotic resistance of canine Staphylococcus intermedius group (SIG)--practical
      implications.
AB  - A total of 221 SIG strains were isolated from clinical samples of canine origin
      submitted to the Diagnostic Laboratory of the Division of Bacteriology and
      Molecular Biology at the Warsaw University of Life Sciences in Warsaw during the
      period 2006-2010. The aim of the study was to investigate the frequency of
      prevalence of methicillin-resistant SIG strains and to determine the MIC values
      of cephalotin, amoxicillin/clavulanic acid, ciprofloxacin, clindamycin,
      gentamicin, chloramphenicol, mupirocin for a collection of randomly selected 79
      strains belonging to Staphylococcus intermedius group (SIG), including 23 mecA
      positive and 56 mecA-negative strains. All isolates were identified as belonging
      to SIG based on their phenotypic properties and PCR amplification of S.
      intermedius-specific fragment of the 16S rRNA gene. The mecA gene was detected in
      26 (12%) of 221 SIG strains. All tested mecA-negative SIG strains were
      susceptible to amoxicillin/clavulanic acid and cephalotin. One of the 56 mecA
      negative SIG strains was resistant to ciprofloxacin, six (11%) to gentamicin. It
      was found that sixteen (29%) of 56 mecA-negative SIG strains were resistant to
      clindamycin. Most of the mecA-positive SIG strains were resistant to
      ciprofloxacin (96%), clindamycin (96%), and gentamicin (96%). Only one MRSIG
      strain was resistant to chloramphenicol. All examined mecA-positive SIG strains
      were found to be susceptible to mupirocin. Our results imply that staphylococcal
      multidrug resistance has become more prevalent, which could lead to difficulties
      in effective treatment. With some resistant strains the only therapeutic
      possibility are antimicrobial agents important in human medicine. New regulations
      for veterinary medicine concerning appropriate therapy of infections caused by
      multidrug-resistat staphylococci are needed.

PMID- 21721405
TI  - The effect of diets supplemented with fish broth and fish oil on the health of
      weaners.
AB  - The aim of this study was to determine the effect of fish-based feed materials,
      as a source of readily available protein contained in fish broth and essential
      polyunsaturated fatty acids (PUFAs) found in fish oil, on the health of piglets
      and rearing results. The experiment was conducted on a commercial pig fattening
      farm. The study involved a total of 80 weaners with an approximate body weight of
      15 kg. The experiment was carried out over a period of 40 days. Feed samples were
      subjected to laboratory analyses. Blood samples were collected from experimental
      group animals to determine serum biochemical and immunological parameters. The
      body weight gains of weaners, mortality rates and average feed intake per animal
      were calculated for the entire experimental period. The addition of fish broth
      and fish oil significantly improved the n3:n6 fatty acid ratio in diets. The
      presence of EPA and DHA in the experimental diet could have had a positive health
      effect on piglets, comparable with that exerted by therapeutic doses of zinc
      often administered to pigs of this age group. During the experiment, feed
      conversion ratio (FCR) gain was considerably reduced in the experimental group,
      with similar daily gains in the control and experimental group.

PMID- 21721406
TI  - The influence of porcine pancreas digestion parameters and islet histomorphology
      on islet isolation outcome.
AB  - Transplantation of the pig islets of Langerhans is considered as the future
      treatment for patients suffering from type I diabetes mellitus. Despite the
      adaptation of modified Ricordi method and highly purified collagenase, the
      results of pancreas digestions are precarious. Selection of proper donor and
      optimal digestion procedure are fundamental. The aim of this study was to assess
      the impact of pancreas procuring parameters on pig islets yield. The pancreata
      were harvested from 69 market sows weighting over 150 kg. After intraductal
      injection of cold collagenase solution pancreata were transported in UW solution
      or under conditions of two layer method (TLM). In laboratory pancreata were
      digested at 37 degrees C according to Ricordi isolation method or stationary in
      the bottle. The particular parameters of isolation procedure were considered as
      substantial. Pig weight, volume of infused collagenase solution, TLM application
      and pancreas dividing before digestion positively affected islet yield.
      Additionally, the influence of pancreatic islet tissue histomorphology on
      isolation outcome was studied. Proper donor selection as well as adequate
      digestion parameters could improve pig islet recovery during islet isolation.

PMID- 21721407
TI  - Evaluation of the risk factors influencing the spread of caseous lymphadenitis in
      goat herds.
AB  - Epidemiological studies on caseous lymphadenitis were carried out in Poland in
      1996 and 2002 among goat herds covered by a milk recording program. Between-herd
      seroprevalence was 13.2% in 1996 and increased to 62.5% in 2002. The average size
      of seropositive herds was statistically significantly higher than that of
      seronegative ones, however there was no statistically significant difference in
      the age between the herds. A statistically significant prevalence ratio (PR) was
      identified and relevant attributable risk for exposed animals (AR(exp)) was
      calculated for the following risk factors: presence of seropositive males in a
      herd (PR = 8.350; AR(exp) = 0.651), presence of superficial abscesses in animals
      (PR = 6.142; AR(exp) = 0.620), presence of respiratory signs (PR = 2.900; AR(exp)
      = 0.393), presence of animals in poor condition in a herd (PR = 2.774; AR(exp) =
      0.390) and occurrence of reproductive failures in a herd (PR = 1.798; AR(exp) =
      0.230). Purchase of animals from abroad, mastitis and husbandry conditions
      (housing system, grazing system, hygienic conditions) were not shown to be
      statistically significant risk factors.

PMID- 21721408
TI  - Is spermiogenesis common or rare in young male European bison aged 2 and 3 years?
AB  - The aim of the present study was to determine how often spermiogenesis occurs in
      young male European bison up to 3 years old. Research was performed on sections
      of the testes and epididymes collected from 51 male bison aged 2-3 years. The
      animals were divided into 2 age groups: young males up to 2 years and young males
      up to 3 years old, with further separation into specimens with or without
      spermiogenesis. The animals were culled during the autumn-winter seasons in 1994
      2008 (after rutting period) in the Bialowieza Primeval Forest. Spermiogenesis in
      the 2-year-old animals was a rare condition found in 16.7% of cases. However, at
      the age of 3 years more than half of the individuals examined (53.3%) had
      spermiogenesis. Young males up to 2 years old with spermiogenesis were
      characterized by a significantly higher body weight and their right testis also
      weighed more than the left testis of the animals without spermiogenesis, the
      difference being on the border of statistical significance. There was no
      significant differences in the body mass and weight of the left testis between
      older animals, up to 3 years old, with or without spermiogenesis. However, young
      males up to 3 years old with spermiogenesis were characterized by a significantly
      higher weight of the right testis than those without spermiogenesis.

PMID- 21721409
TI  - Relationship between receptors for insulin-like growth factor- I, steroid
      hormones and apoptosis-associated proteins in canine mammary tumors.
AB  - In the veterinary literature there are few data concerning the expression of
      insulin-like growth factor type I (IGF-IR) in the canine mammary gland tumors.
      The aim of the present study was the evaluation of IGF-IR expression and its
      correlation to the expression of estrogen receptor alpha (ERalpha) and
      progesterone receptor (PR), proteins: Bcl-2, Bax, p53 in canine mammary gland
      tumors, and also a correlation with other features: bitch's age, tumor diameter,
      histologic type of tumor, degree of histologic malignancy, proliferate activity.
      The study was done on 112 epithelial neoplasms: 21 (19%) were adenoma, 38 (34%)
      complex carcinoma (adenocarcinoma), 47 (42%) simple carcinoma (adenocarcinoma)
      and 6 (5%) solid carcinoma. Histochemistry and immunohistochemistry methods were
      employed. It was shown that more common and/or higher IGF-IR expression in cells
      of canine mammary gland tumors was related to the histologic type of cancer of
      worse prognostic (solid and simple carcinoma), high histologic degree of
      malignancy (III degrees) but the statistical analysis did not reveal any
      significant differences. We observed the high degree of IGF-IR expression in
      tumors which displayed the high ERalpha and PR expression. These results suggest
      the involvement of IGF-IR in the development of hormonosensitive canine mammary
      tumors. Additionally, the significant positive correlation between expression of
      IGF-IR and p53, Bax was found. Our study provides some evidence that interactions
      exist between the IGF-IR and these apoptosis-associated proteins may contribute
      to the development and progression of canine mammary gland tumors. These results
      require further investigations.

PMID- 21721410
TI  - Analysis of integrins and vascular endothelial growth factor isoforms mRNA
      expression in the canine uterus during perimplantation period.
AB  - Integrins are the major receptors within the extracellular matrix (ECM) that
      mediate several functions connected with cell life and metabolism, such as cell
      adhesion, migration, cytoskeletal organization, proliferation, survival, and
      differentiation. A vascular endothelial growth factor (VEGF) is one of the most
      important angiogenic factors. It has been suggested that the expression of this
      gene may play crucial physiological roles in reproductive organs. All
      investigated endometrial tissues were isolated on day 10-12 after mating. Control
      bitches, used in this study, were in metestrus, which was determined according to
      the vaginal cytology and progesterone level in blood. Early pregnancy was
      verified by flushing the uterine horns with PBS. Total RNA was isolated from the
      bitches endometrium by means of the Chomczynski and Sacchi method, treated by
      DNase I, and reverse-transcribed into cDNA. A quantitative analysis of integrins
      alpha2b, beta2 and beta3, VEGF 164, 182 and 188 cDNA was performed by RT-PCR. In
      results we have shown an increased expression of all investigated genes
      (integrins alpha2b, beta2 and beta3, VEGF 164, 182, and 188) in pregnant bitches
      uterus as compared to non-pregnant females (P < 0.001). Our results indicated
      that the expression of genes encoding integrins and vascular endothelial growth
      factors is different in relation to the time of the embryo implantation and it is
      increased in the first period of this process. This may be associated with the
      induction of specific mechanisms responsible for receptivity of uterus following
      the embryo attachment. In addition, all of investigated genes are up-regulated in
      a pregnancy-specific manner and the increased expression of these genes may
      regulate the uterus function during the implantation of canine embryos.

PMID- 21721411
TI  - Differential expression of epidermal growth factor and transforming growth factor
      beta isoforms in dog endometrium during different periods of the estrus cycle.
AB  - Both epidermal growth factor (EGF) and transforming growth factor (TGF) play an
      important physiological role in the processes of proliferation and
      differentiation of several different cell types. However, the expression profiles
      of these factors in domestic bitches endometrium are still poorly recognized. The
      aim of the present study was to identify and analyze the differential expression
      of these factors in various stages of the estrus cycle. Endometrial tissue from
      proestrus (n = 17), estrus (n = 10), day 10 diestrus (n = 15), day 35 diestrus (n
      = 18) and anestrus (n = 25) was collected soon after ovariohysterectomy. Total
      RNA was isolated from the endometrium by means of Chomczynski and Sacchi method,
      treated by DNase I, and reverse-transcribed into cDNA. Quantitative analysis of
      EGF, TGFbeta1, TGFbeta2, and TGFbeta3 cDNA was performed by real-time
      quantitative polymerase chain reaction (RT-PCR). EGF expression in canine
      endometrium was increased in the estrus stage as compared to proestrus (P <
      0.05), day 10 diestrus (P < 0.05), day 35 diestrus (P < 0.01) and anestrus (P <
      0.001). We also found the differences in EGF expression between day 10 and day 35
      of estrus as well as between day 35 of estrus with anestrus (P < 0.05, P < 0.01,
      respectively). The TGFf1 transcript contents were also higher in estrus as
      compared to other stages (P < 0.01). The TGFbeta2 and TGFbeta3 in the estrus
      stage was increased compared to proestrus, day 10 diestrus, day 35 diestrus and
      anestrus (P < 0.05). We proved that expression of EGF and TGFbeta transcript
      isoforms is related to the phase of estrus in bitches and therefore may be
      regulated by specific hormone concentrations during these periods. Our results
      confirm the hypothesis that these growth factors play a role in the regulation of
      biochemical changes in the endometrial tissues during the estrus cycle.

PMID- 21721412
TI  - Dose-dependent in vivo effect of Rhodiola and Echinacea on the mitogen-induced
      lymphocyte proliferation in mice.
AB  - Echinacea purpurea (EP) and Echinacea angustifolia (EA) are ones of the most
      important world's herbs with immunotropic activity. They were traditional
      medicinal plants used by North American Indians for the treatment of various
      illnesses. Now they are cultivated in many countries and are used mainly to treat
      respiratory tract infections. Rhodiola rosea (RR) and Rhodiola quadrifida (RQ)
      are medicinal plants originated from Asia and used traditionally as adaptogens,
      antidepressants, and anti-inflammatory remedies. We previously reported, that
      extracts of underground parts of RR and RQ exhibited immunotropic activity. We
      have demonstrated in pigs that in vitro RR or RQ supplementation of blood
      lymphocyte cultures stimulated T cell proliferative response to Con A in lower,
      and inhibited it in higher Rhodiola extract concentrations. The aim of this work
      was to evaluate the in vivo effect of these herbal remedies on the in vitro
      proliferative response of mouse splenic lymphocytes to another T-cell mitogen-
      Phaseolus vulgaris haemagglutinin (PHA). We have found significant stimulation of
      proliferative response, in comparison to the controls, in mice fed lower doses of
      tested remedies, and inhibition, no effect or lower stimulation, in mice fed
      higher doses of these drugs.

PMID- 21721413
TI  - The study of canine atopic dermatitis involving the isolation of dogs.
AB  - Twenty-seven pruritic dogs were used in this study. When a hypoallergenic diet
      was fed to these 27 dogs for six weeks, none of the dogs showed improvement of
      the pruritus. These dogs had a history and clinical signs of atopic dermatitis
      (AD) as defined by Prelaud's diagnostic criteria. Subsequently, the 27 dogs were
      isolated for observation for two weeks in the hospital. In the isolation room in
      the veterinary clinic, cages and tableware were all stainless steel, and carpet
      was not used. A hypoallergenic diet was continuously fed to the 27 dogs for two
      weeks, during which time they were kept in the isolation room. PVAS (Pruritus
      Visual Analog Scale) was performed prior to starting the isolation, at the start
      of the study and 2 weeks after starting the isolation. In 17 dogs (63%) the
      pruritus improved in the isolation room. A statistically significant reduction (p
      < 0.01) of PLS (Pruritus liners score) was recorded 2 weeks after isolation. It
      was hypothesized that the 17 dogs whose pruritus improved in the isolation room
      had AD caused by an environmental antigen that was not present in the isolation
      room. Pruritus of the remaining 10 dogs (37%) did not improve. For 6/10 dogs, the
      intradermal allergy testing was positive for an environmental antigen. For 4/10
      dogs, the intradermal allergy testing was negative for all environmental
      antigens. Dogs for which sensitivity to an environmental antigen was not
      identified were thought to have atopic-like dermatitis.

PMID- 21721414
TI  - Genetic comparison of Campylobacter jejuni isolated from different cattle farms.
AB  - To compare the genotypes of Campylobacter jejuni, isolates of cattle origin were
      collected from 9 Polish farms and genotyped by ERIC-PCR. We identified 28
      genotypes among the 43 C. jejuni isolates, and demonstrated high genomic
      diversity. The highest level of diversity was observed in strains isolated from
      stanchion-barn animals in opposition to those from the loose-housing system.

PMID- 21721415
TI  - Heterogeneity of methicillin-sensitive Staphylococcus pseudintermedius strains
      isolated from diseased dogs.
AB  - Thirty nine canine S. pseudintermedius strains were examined for antibiotic
      susceptibility and genetic polymorphisms. All strains were methicillin-sensitive
      S. pseudintermedius (MSSP). Resistance to penicillin was most prevalent (66.6%),
      followed by resistance to neomycin (56.4%), erythromycin (53.8%), clindamycin
      (48.7%), chloramphenicol (48.7%), and tetracycline (46.2%). Pulsed-field
      electrophoresis (PFGE) showed a high genetic polymorphism in the investigated
      strains.

PMID- 21721416
TI  - Molecular typing of Staphylococcus aureus based on PCR-RFLP of coa gene and RAPD
      analysis.
AB  - The aim of this study was molecular identification of S. aureus strains isolated
      from mastitic milk samples and establishing the genetic relationship between
      strains isolated from cows belonging to the same herd. In all 43 isolated strains
      the gap gene (930 bp) was amplified, which enabled their affiliation to the
      Staphylococcus genus to be established. PCR-RFLP with AluI endonuclease of the
      gap gene as well as nuc (450 bp) and coa (1130 bp) gene amplification allowed
      precise S. aureus species identification. One hundred percent of the genetic
      relationship between strains was established via RAPD-PCR and coa-typing.

PMID- 21721417
TI  - The evaluation of selected parameters of cellular nonspecific immunity in normal
      and allergic horses.
AB  - The main aim of this study was to compare selected nonspecific immunity
      parameters in 14 allergic and 12 healthy horses. Each animal was assessed
      according to the following parameters: in vitro functional capacity of phagocytic
      cells using the nitro blue tetrazolium chloride reduction test, both spontaneous
      (NBT) and zymozan stimulated (NBTs), and ingestion capacity of phagocytic cells
      using a phagocytic index test (IF) and percentage of phagocytosing neutrophils
      activity (%KF). Differences were demonstrated between the group of allergic
      horses, especially with severe allergy symptoms, and healthy horses in NBTs
      values, with higher values in healthy horses. The values of the phagocytic index
      were significantly higher in horses with allergy.

PMID- 21721418
TI  - Changes in the blood coagulation profile after ovariohysterectomy in female dogs.
AB  - This study investigated changes in the coagulation profile of 10 healthy female
      dogs subjected to ovariohysterectomy. Blood samples were collected three times-
      before, directly after and 24 h after surgery. Plasma samples were analyzed to
      determine thrombin time (TT), prothrombin time (PT), activated partial
      thromboplastin time (APTT), fibrinogen content, D-dimer content and antithrombin
      (AT) III activity. The results revealed post-operative haemostatic system
      disorders related to prolonged APTT, higher fibrinogen and D-dimer concentrations
      and lower levels of AT III activity.

PMID- 21721419
TI  - Local immunity of the respiratory mucosal system in chickens and turkeys.
AB  - This review article presents fundamental mechanisms of the local mucosal immunity
      in selected regions of the respiratory tract in healthy birds and in some
      pathological conditions. The respiratory system, whose mucosa come into direct
      contact with microorganisms contaminating inhaled air, has some associated
      structures, such as Harderian gland (HG), conjunctive-associated lymphoid tissue
      (CALT) and paranasal glands (PG), whose participation in local mechanisms of the
      mucosal immunity has been corroborated by numerous scientific studies. The nasal
      mucosa, with structured clusters of lymphoid tissue (NALT - nasal-associated
      lymphoid tissue) is the first to come into contact with microorganisms which
      contaminate inhaled air. Lymphoid nodules, made up of B cells with frequently
      developed germinal centres (GC), surrounded by a coat of CD4+ cells, are the
      major NALT structures in chickens, whereas CD8+ cells are situated in the
      epithelium and in the lamina propria of the nasal cavity mucosa. Studies into
      respiratory system infections (e.g. Mycoplasma gallisepticum) have shown the
      reactivity of the tracheal mucosa to infection, despite a lack of essential
      lymphoid tissue. Bronchus-associated lymphoid tissue (BALT) takes part in
      bronchial immune processes and its structure, topography and ability to perform
      defensive function in birds is largely age-dependent. Mature BALT is covered by a
      delicate layer of epithelial cells, called follicle-associated epithelium (FAE).
      Germinal centres (GC), surrounded by CD4+ cells are developed in most mature BALT
      nodules, while CD8+ lymphocytes are dispersed among lymphoid nodules and in the
      epithelium, and they are rarely present in GC. Macrophages make up the first line
      of defence mechanisms through which the host rapidly responds to microorganisms
      and their products in the respiratory mucosal system. Another very important
      element are polymorphonuclear cells, with heterophils being the most important of
      them. Phagocytic cells obtained from lung lavages in birds are referred to as
      FARM (free avian respiratory macrophages). Their number in chickens and turkeys
      is estimated to be 20 times lower than that in mice and rats, which indicates a
      deficit in the first-line of defence in the birds' respiratory system. There are
      numerous B cells and antibody secreting cells (ASC) present throughout the
      respiratory system in birds. Their role comes down to perform antigen-specific
      protection by producing antibodies (IgM, IgY or IgA class) as a result of contact
      with pathogenic factors.

PMID- 21721420
TI  - Bluetongue vaccines in Europe.
AB  - The article reviews the history, present status and the future of BT vaccines in
      Europe. So far, an attenuated (modified live viruses, MLV) and inactivated virus
      vaccines against BT were developed and used in the field. Moreover, the virus
      like particles (VLPs) produced from recombinant baculovirus, and live recombinant
      vaccinia or canarypox virus-vectored vaccines were tested in the laboratory. The
      main aims of BT vaccination strategy are: to prevent clinical disease, to reduce
      the spread of the BTV in the environment and to protect movement of susceptible
      animals between affected and free zones. Actually, all of the most recent
      European BT vaccination campaigns have used exclusively inactivated vaccines. The
      use of inactivated vaccines avoid risk associated with the use of live-attenuated
      vaccines, such as reversion to virulence, reassortment of genes with field
      strain, teratogenicity and insufficient attenuation leading to clinical disease.
      The mass vaccinations of all susceptible animals are the most efficient
      veterinary method to fight against BT and successful control of disease. The
      vaccination of livestock has had a major role in reducing BTV circulation and
      even in eradicating the virus from most areas of Europe.

PMID- 21721421
TI  - Laparoscopic procedures in dogs and cats.
AB  - Laparoscopic procedures are gaining wider application in veterinary medicine. The
      following article contains description of indispensable equipment for performing
      surgical procedures with use of laparoscopic technique and reviews some
      laparoscopic procedures which found application in veterinary medicine.

PMID- 21721422
TI  - Transgenic mammalian species, generated by somatic cell cloning, in biomedicine,
      biopharmaceutical industry and human nutrition/dietetics--recent achievements.
AB  - Somatic cell cloning technology in mammals promotes the multiplication of
      productively-valuable genetically engineered individuals, and consequently allows
      also for standardization of transgenic farm animal-derived products, which, in
      the context of market requirements, will have growing significance. Gene farming
      is one of the most promising areas in modern biotechnology. The use of live
      bioreactors for the expression of human genes in the lactating mammary gland of
      transgenic animals seems to be the most cost-effective method for the
      production/processing of valuable recombinant therapeutic proteins. Among the
      transgenic farm livestock species used so far, cattle, goats, sheep, pigs and
      rabbits are useful candidates for the expression of tens to hundreds of grams of
      genetically-engineered proteins or xenogeneic biopreparations in the milk. At the
      beginning of the new millennium, a revolution in the treatment of disease is
      taking shape due to the emergence of new therapies based on recombinant human
      proteins. The ever-growing demand for such pharmaceutical or nutriceutical
      proteins is an important driving force for the development of safe and large
      scale production platforms. The aim of this paper is to present an overall survey
      of the state of the art in investigations which provide the current knowledge for
      deciphering the possibilities of practical application of the transgenic
      mammalian species generated by somatic cell cloning in biomedicine, the
      biopharmaceutical industry, human nutrition/dietetics and agriculture.

PMID- 21721423
TI  - The possibilities of practical application of transgenic mammalian species
      generated by somatic cell cloning in pharmacology, veterinary medicine and
      xenotransplantology.
AB  - Cloning of genetically-modified mammals to produce: 1) novel animal bioreactors
      expressing human genes in rens, urinary bladder and the male accessory sex
      glands, as well as 2) porcine organs suitable in pig-to-human
      xenotransplantology, could offer new advantages for biomedical purposes. So too
      does the generation and/or multiplication of genetically-engineered cloned
      animals in order to produce: 3) physiologically-relevant animal models of serious
      monogenic human diseases and 4) prion disease-resistant small as well as large
      animals (i.e., rodents, ruminants). The basic purpose of this paper is to
      overview current knowledge deciphering the possibilities of using transgenic
      specimens created by somatic cell nuclear transfer in medical pharmacology,
      veterinary medicine, agriculture, transplantational medicine and immunology.

PMID- 21721424
TI  - Patients with non-sT-segment elevation myocardial infarction present with more
      severe systolic and diastolic dysfunction than patients with unstable angina.
AB  - BACKGROUND: Patients with non ST-segment elevation acute coronary syndrome
      (NSTEACS) present with diverse clinical, electrocardiographic, cardiac biomarker,
      echocardiographic and angiographic characteristics. We sought to determine
      whether there was any difference in the indices of left ventricular systolic and
      diastolic function among subgroups of patients with NSTEACS. MATERIAL AND METHOD:
      We studied 121 consecutive patients (mean age 68.6 +/- 11.3 years, 45% male) with
      NSTEACS who underwent comprehensive echocardiography within 48 hours of
      admission. Two-dimensional and Doppler echocardiography was performed for the
      evaluation of left ventricular systolic and diastolic function. RESULTS: Non ST
      segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) were
      reported in 59% and 41% of patients, respectively. Clinical characteristics (such
      as age, gender, cardiovascular risk factors, prior myocardial infarction and
      revascularization, medication) were not significantly different between patients
      with NSTEMI and UA. Patients with NSTEMI were more likely to have wall motion
      abnormalities and lower left ventricular ejection fraction (p < 0.05) as compared
      to those with UA. Diastolic dysfunction was significantly more frequent and more
      severe in patients with NSTEMI than in those with UA. CONCLUSION: Among patients
      with NSTEACS, left ventricular systolic and diastolic dysfunction was more
      frequent and more severe in patients with NSTEMI that in those with UA. These
      findings may be used to characterize the sicker group among patients with
      NSTEACS.

PMID- 21721425
TI  - Fractional flow reserve guided coronary revascularization in drug-eluting era in
      Thai patients with borderline multi-vessel coronary stenoses.
AB  - BACKGROUND: Previous studies have shown the cost benefit of fractional flow
      reserve (FFR)--guided coronary revascularization in the patient with multivessel
      borderline coronary artery stenoses. However; they have been performed in the
      Bare-metal stent era. It is a challenge to demonstrate the benefit of the FFR
      guided coronary revascularization in the patient with multivessel coronary
      disease (MVD) in the drug-eluting era in Thai patients. MATERIAL AND METHOD:
      Forty-nine patients with MVD (71 stenotic vessels) underwent FFR-guided
      revascularization (FFR group) compared with forty-nine patients with MVD (79
      stenotic vessels) underwent traditional PCI (Traditional group) on the basis of
      visual estimation of the stenotic lesion. PCI has been performed in the FFR group
      patient with FFR value < or =0.75, whereas those with FFR value > or = 0.75
      continued on medical treatment. The event rates of chest pain, repeat
      revascularization, hospitalization, myocardial infarction and death were compared
      between both groups. Total costs incurred in the catheterization laboratory,
      including the cost of stent, balloon, pressure guide wire, contrast media and
      other supplies, were computed between both groups. RESULTS: In FFR group: in 46
      vessels, FFR was 0.87 +/- 0.06 and PCI was avoided, the other 25 vessels,
      baseline FFR was 0.65 +/- 0.09 and were underwent PCI. Two patients proceed CABG
      In the traditional PCI group: 79 vessels were underwent PCI. In comparison of
      event free survival between the FFR and the traditional PCI groups during follow
      up (mean follow-up 8.27 +/- 5.45 vs. 9.49 + 5.39 months), they were not different
      in MACE, chest pain, repeat revascularization, hospitalization, myocardial
      infarction and death (8.2% vs. 13.3%, p = 0.33). The average total cost saving
      per patient was 63,290 Baht (p < 0.001). CONCLUSION: For patients with borderline
      MVD, FFR-guided coronary revascularization with drug eluting stent placement
      could save a total cost per patient at 63,290 Bath without compromising safety.

PMID- 21721426
TI  - Late gadolinium enhancement from cardiac magnetic resonance in ischemic and non
      ischemic cardiomyopathy.
AB  - BACKGROUND: Diagnosis of coronary artery disease in patients with heart failure
      with systolic dysfunction usually requires coronary angiography. Cardiac magnetic
      resonance (CMR) is an accurate tool for the assessment of myocardial scar which
      may be the major cause of left ventricular systolic dysfunction. OBJECTIVE: This
      study was to determine the prevalence and the difference in pattern of late
      gadolinium enhancement (LGE) between patients with ischemic (ICM) and non
      ischemic cardiomyopathy (NICM). MATERIAL AND METHOD: We enrolled 98 patients with
      heart failure and left ventricular systolic dysfunction with left ventricular
      ejection fraction less than 50%. Allpatients underwent CMR. CMR protocol included
      functional study and assessment of LGE. Left ventricular volume and ejection
      fraction was measured. The presence and extent of LGE including its pattern were
      assessed. RESULTS: There were 58 patients with ICM and 40 patients with NICM.
      Patients with NICM had a lower left ventricular ejection fraction than those with
      ICM with a similar left ventricular wall thickness. LGE was detected in 53
      patients with ICM (91.5%) and 10 patients with NICM (25%). LGE pattern was
      transmural or subendocardial pattern in patients with ICM and midwall scar in
      those with NICM. CONCLUSION: The presence and pattern ofLGE can differentiate
      systolic heart failure from ICM and NICM.

PMID- 21721427
TI  - D-dimer plasma levels in NSTE-ACS patient.
AB  - BACKGROUND: Acute Coronary Syndrome (ACS) occurs when a vulnerable plaque
      ruptures and induces platelet aggregation and coagulation process at the rupture.
      Thrombogenesis is the final process that forms a clot in the coronary lumen
      causing myocardial injury. Plasma D-dimer, a primary degradation product and
      circulating marker offibrin turnover, serves as a direct marker of ongoing
      fibrinolysis in site of coronary artery occlusion. OBJECTIVE: To determine the
      correlation between plasma D-dimer levels and severity of coronary artery
      obstruction based on angiographic data that is composed of the number of coronary
      arteries affected and the percentage of maximum stenosis of coronary artery lumen
      in non-ST elevation ACS (NSTE-ACS) patients. MATERIAL AND METHOD: NSTE-ACS
      patients who admitted in Siriraj hospital duringJune 2009 and March 2010 were
      enrolled. Conditions that increased plasma D-dimer other than NSTE-ACS were
      excluded. Demographic characteristics were assessed by a standardized
      questionnaire. Plasma D-dimer was measured and coronary angiography was performed
      to evaluate severity of coronary artery stenosis. RESULTS: Total of 74 NSTE-ACS
      patients were enrolled (29 in unstable angina and 45 in non-ST elevation
      myocardial infarction). Mean age of these patients (54.1% in female and 45.9% in
      male) were 66 years. D-Dimer was significantly increased with the number of
      coronary arteries affected (p = 0.03). In non-significant and single coronary
      artery disease (CAD) patients, median D-dimer was 406 (178-2,788) mcg/L. In
      multivessel CAD, median D-dimer was 941 (131-7,110) mcg/L. D-dimer levels had a
      trend to be increased with percentage of maximum stenosis of coronary artery
      lumen; atheromatosis, (p = 0.30). In mild and moderate atheromatosis (coronary
      artery stenosis < 70%), median D-dimer was 479 (182-5902) mcg/L while median D
      dimer was 789 (131-7110) mcg/L in severe atheromatosis (coronary artery stenosis
      > 70%). Moreover plasma D-dimer levels correlated with complication of NSTE-ACS
      (Congestive heartfailure; p < 0.001, arrhythmia; p = 0.007 and death; p = 0.009)
      and was increased in patients who underwent treatment with CABG more often than
      those who received PCI and medication treatment alone. D-dimer also correlated
      with serum creatinine (r = 0.517, p < 0.001), creatinine clearance (r = -0.463, p
      < 0.001), troponin-T level (r = 0.381, p < 0.001) and left ventricular ejection
      fraction (r = -0.368, p = 0.002). CONCLUSION: D-dimer is useful coagulation
      marker use to evaluate extent of coronary affected and may predict in-hospital CV
      complication. However, other conditions that increased plasma D-dimer also
      excluded.

PMID- 21721428
TI  - Comparison of aortic diameter in normal subjects and patients with systemic
      hypertension.
AB  - BACKGROUND: Standard aortic root dimensional measurement by the two dimensional
      echocardiography should be routinely performed in all patients. There is limited
      data on the normal reference on Thai population. OBJECTIVE: Aims of this study
      were (1) to determine the normal reference of aortic root dimension in Thai
      population and (2) to determine the difference in the aortic root size in
      patients with hypertension comparing with normal population. MATERIAL AND METHOD:
      We retrospectively reviewed 81 patients who had the transthoracic
      echocardiographic examinations in our echocardiographic lab and had the aortic
      root measurement data. The patients with ascending aortic aneurysm, aortic
      dissection, aortic stenosis and/or regurgitation more than mild in degree,
      Marfan's syndrome and annuloaortic ectasia were excluded. The echocardiographic
      data of were collected; the aortic root dimensions at four levels; aortic valve
      annulus, sinus of Valsava, sinotubular junction and tubular parts. Hypertension
      was indentified if the patient had the prior diagnosis of hypertension and on
      antihypertensive medications, or who had blood pressure more than 140/90 mmHg for
      two or more occasions. RESULTS: Eighty-one patients were enrolled. Sixty patients
      (74.1%) were diagnosed hypertension. Mean age was 66.9 +/- 11.2 years in
      hypertensive patients and 49.1 +/- 16.4 years in normotensive patients. Normal
      reference values based on 95% upper normal limit of aortic valve annulus, sinus
      of Valsava, sinotubular junction and tubular part were 2.30 (2.21-2.38), 3.56
      (3.35-3.77), 2.79 (2.61-2.97), and 3.36 (3.13-3.59), respectively. Patients with
      hypertension had significant larger sinus of Valsava and tubular part of aortic
      root than patients with normotension. CONCLUSION: We reported a normal reference
      value for aortic root size in Thai population. The aortic root sizes are
      influenced by hypertensive status, age and gender.

PMID- 21721429
TI  - Hypertension audit in clinical practice based in Thailand (HABIT).
AB  - This cross-sectional survey aimed to determine blood pressure (BP) control, risk
      factors, co-morbidities and end-organ damage among Thai hypertensive patients.
      Between February and April 2007, we enrolled 2007 out-patient hypertensives who
      were treated for > or =6 months. However, baseline assessment could be obtained
      from only 1914 cases (male:female = 4:3; mean age: 61.9 +/- 11.7 years) and 1807
      cases were eligible for BP evaluation (average BP: 140.45 +/- 19.99 / 77.84 +/-
      12.51 mm Hg). Overall BP normalization (BP < 140/90 mmHg) was 51%, but it was 44%
      when diabetic patients whose BP's had to be < 130/80 mmHg were taken into
      account. Common risk factors/co-morbidities were hypercholesterolemia (66%),
      metabolic syndrome (36%), diabetes mellitus (35%) and obesity (32%). Monotherapy
      was found in 26%, 2 medications in 44% and > or =3 medications in 29%. Calcium
      channel blockers were prescribed in 49%, diuretics in 45%, beta-blockers in 44%
      and angiotensin-converting enzyme inhibitors in 38%. Three quarters of physicians
      were aware of target blood pressure according to the latest hypertension
      guidelines. In conclusion, BP normalization rate in 2007 audit was better than in
      the 2003 audit (51% vs. 44%). Campaigns targeting the commonest risk factors,
      hypercholesterolemia and metabolic syndrome, should be a priority.

PMID- 21721430
TI  - Validity and reliability assessment of the Siriraj Asthma Control Questionnaire.
AB  - OBJECTIVE: The present study assessed the validity and reliability of the Siriraj
      Asthma Control Questionnaire in Asthma Clinic, Siriraj Hospital. MATERIAL AND
      METHOD: The data of the questionnaire responses and spirometric results from 20
      randomized asthmatic patients in the clinic including the record of 3 visits for
      each subject. The validation was performed by Kruskal-Wallis test comparing the
      scores with the level of asthma control determined by physicians according to
      GINA guideline. Internal consistency reliability was analyzed by Cronbach's
      alpha. RESULTS: Sixty questionnaires from 20 patients with age 29-73 years were
      analyzed. There were 40 controlled, 7 partly controlled and 13 uncontrolled
      visits. The scores from 5-items questionnaires and 6-items clinical score were
      significantly associated with the physician-diagnosed groups (i.e., controlled,
      partly controlled and uncontrolled groups). Median scores (min, max) were 0 (0,
      5), 2 (0, 6), 4 (0, 12) respectively, (5-items, p < 0.001) and 2 (0, 7), 3 (1,
      7), 6 (2,15) respectively, (6-items, p < 0.001). Internal consistency reliability
      of both 5-items questionnaire and 6-items clinical score were within the
      acceptable range (0.829 and 0.708 respectively). 5-items questionnaire is more
      associated with the physician diagnosed group and more consistent than 6-items
      clinical score. Further analysis revealed cutoff point at 2.5 to separate
      uncontrolled from controlled or partly controlled patient with sensitivity 76.9%
      and specificity 89.4% and cutoff point at 1.5 to separate uncontrolled or partly
      controlled from controlled patient with sensitivity 70.0% and specificity 85.0%.
      CONCLUSION: The validity and reliability of Siriraj Asthma Control Questionnaire
      is acceptable and might be used in the clinical practice and research in Thai
      asthmatic patients.

PMID- 21721431
TI  - Assessment of cerebrospinal fluid (CSF) beta-amyloid (1-42), phosphorylated tau
      (ptau-181) and total Tau protein in patients with Alzheimer's disease (AD) and
      other dementia at Siriraj Hospital, Thailand.
AB  - BACKGROUND: The combination of decreased cerebrospinal fluid (CSF) levels of beta
      amyloid (1-42) and increased levels of phosphorylated tau (ptau-181) or total tau
      protein are known to be biomarkers ofAlzheimer's disease (AD). These biomarkers
      can also be used as predictors of disease progression in persons with mild
      cognitive impairment. Utilizing biomarkers to differentiate Alzheimer's disease
      (AD) against non-Alzheimer dementia (non-AD) needs to be explored. OBJECTIVE: To
      evaluate the clinical use ofCSF biomarker: beta-amyloid (1-42), phosphorylated
      tau (ptau-181) and total tau protein for distinguishing Alzheimer's disease (AD)
      from non-Alzheimer dementia (non-AD) in Thai patients. MATERIAL AND METHOD:
      Thirty patients diagnosed of dementia during 2005-2007 at Siriraj hospital were
      offered CSF analysis for beta-amyloid (1-42), phosphorylated tau (ptau-181) and
      total tau protein. Diagnosis of dementia was performed by a concensus diagnostic
      group utilizing a standard criteria for diagnosis of AD and other dementia. All
      CSF testing was performed by Enzyme-Linked Immunoassay (ELISA) technique of the
      INNOTESTM to analyze these biomarkers. RESULTS: Thirty demented patients were
      recruited in the study. Fourteen had AD and 16 had non-AD including 5 vascular
      dementia, 5 normal pressure hydrocephalus, 4 frontotemporal lobar degeneration
      and others. Mean age of the AD group was 67.79 (12.30) and that of non-AD group
      was 65.75 (15.04). Twelve AD had decreased levels of CSF /3-amyloid (1-42) (less
      than 487 pg/ml). Only one patient with AD had increased CSF phosphorylated tau
      (ptau-181) (more than 61 pg/ml). None of theAD patient had increased CSF total
      tau (more than 425 pg/ml). Eight patients with non-AD had decreased levels of CSF
      p-amyloid (1-42), one had increased CSF total tau protein, and none had increased
      CSF phosphorylated tau (ptau-181) protein. The sensitivity of decreased level of
      CSF beta-amyloid (1-42) in AD against non-AD dementia was 85.71%. Those of
      increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against
      non-AD dementia were 7.14% and 0% consecutively. The specificity of decreased
      level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 50%. The
      specificity of increased CSF total tau and phosphorylated tau (ptau-181) protein
      in AD against non-AD dementia were 100% and 93.75% sequentially. The combination
      of 2 biomarkers would increase specificity but decrease sensitivity. CONCLUSION:
      CSF biomarker analysis should be encouraged to use as diagnostic aid in memory
      clinic especially to help diagnosis of atypical presentation of AD. The
      usefulness of longitudinal data needs to be explored.

PMID- 21721432
TI  - Reliability of the Thai version of SF-36 questionnaire for an evaluation of
      quality of life in multiple sclerosis patients in multiple sclerosis clinic at
      Siriraj Hospital.
AB  - BACKGROUND: To study the application, validity and reliability of a Thai version
      of SF-36 questionnaires in Thai multiple sclerosis (MS) patients. MATERIAL AND
      METHOD: An evaluation of quality of life using a Thai version of SF-36 was
      performed in 70 MS or clinical isolated syndrome (CIS) patients. STATISTICAL
      ANALYSIS: Measurement of internal consistency was done by Cronbach's alpha
      coefficient and inter-item correlation; measurement of The test-retest
      reliability assessing consistency of the measure was done by Pearson correlation.
      RESULTS: There were 55 clinical definite MS patients, 12 laboratory-supported
      definite MS patients and 3 clinical-probable MS patients, according to Poser
      criteria. MS types were classified as PP-primary progressive MS(2), RR-relapsing
      remitting MS (59), SP-secondary progressive MS(3) and CIS(6). Internal
      consistency measured by Cronbach's Alpha exceeded 0.7 except social functions,
      which was 0.69. The item correlation coefficient ranged from 0.47-0.88.
      Reliability of test-retest all items determined by Pearson correlation was
      significant, ranging from 0.84-0.94. CONCLUSION: Thai version SF-36 questionnaire
      is reliable for the assessment of quality of life in Thai multiple sclerosis
      patients.

PMID- 21721433
TI  - Accuracy and clinical utility of a portable coagulometer in an emergency setting.
AB  - BACKGROUND: There are limited data concerning accuracy of portable coagulometer
      in emergency setting. OBJECTIVE: To evaluate the accuracy of the CoaguChek XS
      international normalized ratio (INR) monitor compared to the standard laboratory
      method in emergency department. MATERIAL AND METHOD: Emergency room patients who
      required coagulation test were recruited. Parallel INR measurements between
      portable coagulometer and standard laboratory were performed. RESULTS: Fifty-five
      patients with a mean age of 59.1 +/- 15.7 years (20-87) were included. Men
      constituted 56.4%. Indications for testing were as follows: acute stroke 72.7%;
      abnormal bleeding 7.3%; taking anticoagulant 7.3%; and others 12.7%. Mean time +/
      SD used from blood drawn to INR result report was 65.02 +/- 24.5 minutes for
      standard laboratory and 1 minute for portable coagulometer. Mean difference of
      INR result from portable coagulometer and standard laboratory was 0.02 +/- 0.13
      and an excellence correlation between INR (r = 0.969) was demonstrated. There was
      no significant difference between the INR value from the two methods (p = 0.34).
      CONCLUSION: The use of portable coagulometer (CoaguChek XS) in emergency setting
      was accurate and required less time. Acute ischemic stroke patients are likely to
      benefit from a timely clinical decision making for thrombolysis medication.

PMID- 21721434
TI  - Risk factors for developing delirium in older patients admitted to general
      medical wards.
AB  - BACKGROUND: Delirium in older patients is common and leads to poor clinical
      outcomes. It is, however, preventable if its risk factors are identified and
      modified accordingly. OBJECTIVE: To determine risk factors associated with
      delirium in hospitalized older patients admitted to general medical wards at
      Siriraj Hospital. MATERIAL AND METHOD: A prospective observational study was
      conducted at general medical wards, Siriraj Hospital. All consecutive patients
      aged 70 years or older admitted during study period were assessed and followed
      until discharge. A diagnosis of delirium was made if patients developed symptoms
      which fulfilled DSM IV criteria. Information regarding demographic data, co
      morbid illnesses, preexisting cognitive status and functional status was
      collected at admission. Factorf associated with delirium were analyzed using
      logistic regression models. RESULTS: Risk factors associated with developing
      delirium identified from univariate analysis were female gender, age more than 80
      years-old, having 4 or more co-morbidities, azothemia, hyponatremia, presence of
      infection, severe illness, preexisting dementia, depression, and impaired basic
      activities of daily living. After adjusted in multivariate analysis; factors
      those remained statistically significant were preexisting dementia (OR = 5.52,
      95% CI = 2.51-12.14), severe illness (OR = 5.18, 95% CI = 2.10-12.76) presence of
      infection (OR = 2.54, 95% CI = 1.15-5.61) and azothemia (OR = 2.55, 95% CI =
      1.205.40). CONCLUSION: Pre-existing dementia and illness severity were strongly
      associated with developing delirium in older patients in the present study, which
      is concordant with previous studies. Other factors such as presence of infection
      and azothemia are modifiable factors that could potentially be important targets,
      along with other factors identified in the present study, for implementing
      intervention in order to prevent delirium in this population.

PMID- 21721435
TI  - Use of saline flush to prevent filter clotting in continuous renal replacement
      therapy without anticoagulant.
AB  - OBJECTIVE: This study aims to compare filter life between saline flushed and non
      saline flushed strategies in critically ill patients at high risk of bleeding who
      are undergoing CRRT without anticoagulation. MATERIAL AND METHOD: A cohort of 121
      critically ill patients with severe acute kidney injury (AKI) requiring CRRT in
      the medical intensive care unit (ICU) and cardiac care unit (CCU) of a tertiary
      care academic center were included. 78 of them used saline flushed through CRRT
      circuit. RESULTS: There was no significant difference between the two groups of
      treated patients in baseline characteristics, including the extent of
      coagulopathy and platelet count. Mean circuit survival was 21.2 h for circuits
      using saline flush and 20.4 h for those using non-saline flush (p = 0.8).The
      Kaplan-Meier curves revealed no difference in circuit survival time between
      saline flushed and non-saline flushed groups (p = 0.8). CONCLUSION: The use of
      saline flush into pre-filter site of CRRT circuit does not provide any benefit on
      circuit clotting prevention in high-risk of bleeding patients requiring CRRT
      without anticoagulant.

PMID- 21721436
TI  - Nephrotic syndrome in elderly patients: three years experience at Siriraj
      Hospital.
AB  - BACKGROUND: The population age is being high and nephotic syndrome is a common
      renal disease. OBJECTIVE: To find the etiology and clinical manifestations of
      nephrotic syndrome in the elderly patients who underwent renal biopsy at Siriraj
      hospital including management and outcome. MATERIAL AND METHOD: Retrospective
      study in 76 nephrotic patients whose age > or =50 years and underwent renal
      biopsy between 2005-2007. RESULTS: Seventy six nephrotic patients with age ranged
      from 50-84 years were analysed. Primary glomerulonephritis diseases were found
      more than secondary causes (5:2). The two most common glomerulonephritis were
      membranous GN and focal/segmental glomerulosclerosis. The etiology of common
      secondary GN was lupus nephtitis 11.84% following by diabetic nephropathy and
      amyloidosis. The patients received immunosuppressive drugs and complete response
      was found in 51%, partial response 10.2%, no response was 2% and no
      immunosuppressive therapy 36.7%. There was 1 patient died of septicaemia.
      CONCLUSION: Nephrotic syndrome in the elderly patients were not uncommon. The
      causes should be identified for prompt management and excellent outcome.

PMID- 21721437
TI  - Evaluation of atherosclerosis, arterial stiffness and related risk factors in
      chronic hemodialysis patients in Siriraj Hospital.
AB  - BACKGROUND: Additional to traditional risk factors for cardiovascular disease
      (CVD), recent evidence demonstrates that nontraditional risk factors such as high
      sensitive C-reactive protein (hsCRP), hyperhomocysteinemia and vascular
      calcification may cause progressive atherosclerosis in hemodialysis patients.
      OBJECTIVE: We aim to determine the prevalence of atherosclerosis and assess the
      arterial stiffness and related risk factors. MATERIAL AND METHOD: Common carotid
      artery intima-media thicknesses (CIMT), atherosclerotic plaque occurrence were
      determined by B-mode ultrasonography in 105 hemodialysis patients (mean age, 53
      +/- 15.5 years; mean dialysis duration 82 +/- 59.5 months). A history of
      clinically significant atherosclerotic vascular disease was elicited by patient
      questionnaire and verified by careful patient chart review and physical
      examination. Cardiovascular ankle index (CAVI) was use to assess arterial
      stiffness. Serum biochemical marker for traditional risk factors, hsCRP and
      homocysteine were measured by standard method. RESULTS: Atherosclerotic vascular
      disease (defined by a history of CVD or presence of atherosclerotic plaque) was
      present in 79% of patients. Compared to non-atherosclerotic group, the mean CIMT
      and serum hsCRP in atherosclerotic group was higher (1.9 +/- 0.8 mm vs. 0.8 +/-
      0.6 mm, p < 0.001; 6.5 +/- 8.8 mg/L vs. 3.3 +/- 3.5 mg/L, p = 0.03,
      respectively), while other biochemical markers were not significantly different,
      as well as the percentage of abnormal CAVI (69% vs. 54.5%, p = 0.28). CAVI was
      positively correlated with maximum carotid intima-meida thickness (r = 0.44, p <
      0.001). CAVI was also significantly greater in patients with carotid plaque (soft
      plaque (p < 0.05) and calcified plaque (p < 0.05)) compared with patients without
      carotid plaque. CONCLUSION: A high prevalence of atherosclerosis and arterial
      stiffness was observed in hemodialysis patients. Carotid atherosclerosis is
      associated with an increased inflammatory marker (hsCRP). CAVI may be a useful
      index to assess arterial stiffness and associated with arterial intima-media
      thickness.

PMID- 21721438
TI  - Acute kidney injury in primary nephrotic syndrome: report of nine cases in
      Siriraj Hospital.
AB  - Acute kidney injury is a rare but important complication of nephrotic syndrome.
      We demonstrated here nine patients with nephrotic syndrome and oliguric renal
      failure in Siriraj Hospital during 2007-2009. Renal biopsy was done in every
      patient. The results were focal and segmental glomerulosclerosis (FSGS) in three
      patients, minimal change disease in four patients and collapsing focal segmental
      glomerulosclerosis in two patients. Seven patients had dramatic response to
      corticosteroid treatment within a few weeks and had rapid recovery of renal
      function. The exact mechanism of idiopathic renal failure is not well understood
      but it might be related to reduction in ultrafiltration coefficient of the
      glomeruli.

PMID- 21721439
TI  - The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis
      patients receiving erythropoietin: a meta-analysis.
AB  - BACKGROUND: To determine the impact of adjuvant ascorbic acid therapy on
      erythropoietin-hyporesponsive, anemic patients undergoing hemodialysis. DATA
      SOURCES: The online databases of PubMed, Cochrane library, IPA, CINAHL, EMBASE,
      clinicaltrial.gov, WHO trial registry and PyschINFO were used. STUDY SELECTION:
      Studies comparing ascorbic acid to a control, with participants receiving
      erythropoietin and hemodialysis, and reported outcomes for hemoglobin or
      transferring saturation. DATA EXTRACTION: Two independent researchers reviewed
      titles and abstracts to determine relevance and extracted study design, dose,
      duration, baseline values, and outcomes. DATA SYNTHESIS: Five studies met all the
      criteria and were used for final analysis. The calculated weighted mean
      difference between hemoglobin in the ascorbic acid group versus the control group
      was 0.96 g/dL (95% CI, 0.78 to 1.14). The calculated weighted mean difference
      between transferrin saturation in the ascorbic acid treatment group versus the
      control was 8.26% (95% CI, 6.59 to 9.94). CONCLUSION: Adjuvant ascorbic acid
      significantly raises hemoglobin levels in patients with erythropoietin
      hyporesponsiveness undergoing hemodialysis. The significant rise in transferrin
      saturation indicates that this positive effect on erythropoietin response may be
      due to increased iron utilization.

PMID- 21721440
TI  - Genetic polymorphism of low-density lipoprotein receptor did not affect treatment
      outcome of chronic hepatitis C genotype 3.
AB  - BACKGROUND: The low-density lipoprotein receptor (LDL-R) has been proposed to
      function as a receptor for the hepatitis C virus (HCV) entry. Polymorphism of LDL
      R gene may influence the clearance of virus and response to treatment. This study
      was conducted to evaluate the association of LDL-R gene polymorphism and the
      response to antiviral treatment in patients with chronic HCV infection. MATERIAL
      AND METHOD: A total of 112 naive patients with HCV genotype 3 were enrolled in
      the study. All patients were treated with a combination of pegylated interferon
      and ribavirin for 24 weeks. Polymerase chain reaction combined with restriction
      fragment length polymorphism was used to detect the polymorphism at the LDL-R
      gene intron 11 loci, including intron1, intron 3.1, intron 3.2, intron 4, intron
      6, exon 8, intron 11, intron 13, intron 14 and 3'UTR-2 SNPs in intron 16 region.
      Comparisons of genotype and allele frequency between responders and nonresponders
      were analyzed. RESULTS: Patients had a mean age of 54 years and 43% were male.
      Mean HCVRNA viral load and alanine aminotransferase level were 6.3 log, IU/mL and
      100 IU/L, respectively. Sustained virological response, relapse and no response
      were documented in 68.7%, 17.9% and 13.4%, respectively. Baseline characteristics
      including age, sex, body weight, aminotransferase levels and HCV RNA viral load
      were similar between responders and nonresponders. No statistical difference was
      found for either genotype distribution or allele frequency among responders and
      nonresponders. CONCLUSION: This study did not provide the evidence for a role of
      LDL-R polymorphism the response to antiviral treatment in patients with HCV
      genotype 3. This indicates that a genetic component via the LDL-R may not control
      HCV treatment outcome in HCV genotype 3

PMID- 21721441
TI  - Efficacy of disposable needles versus angiocath needles for therapeutic abdominal
      paracentesis.
AB  - BACKGROUND: Disposable needle and angiocath needle are the two most commonly used
      needles for therapeutic abdominal paracentesis. The present study aims to compare
      the efficacy and complication rate between disposable needles and angiocath
      needles for therapeutic abdominal paracentesis. MATERIAL AND METHOD: The present
      study was an open-labelled study of patients indicated for therapeutic abdominal
      paracentesis at Siriraj Hospital during June to December 2009. Patients were
      assigned by physicians to either the disposable needle group (disposable needle
      No.18 used) or the angiocath group (angiocath needle No.16 used). Efficacy and
      complications were compared. RESULTS: A total of 100 patients were assigned to
      the disposable group, and 100 patients to the angiocath group. The disposable
      needle group had higher success rate by single attempt (97% vs. 84%, p = 0.006)
      and less failure (0 vs. 6%, p = 0.013). However the ascites flow rate in the
      angiocath group was significantly greater (mean 67.1 vs. 53.1 ml/min, p = 0.012).
      Complications were fewer in the disposable needle group, particularly of
      abdominal wall hematoma (1% vs. 8%, p = 0.035). Traumatic tapping also occurred
      less often in the disposable needle group but was not statistically significant
      (3% vs. 9%, p = 0.134). CONCLUSION: Compared with angiocath needles, disposable
      needles used for therapeutic abdominal paracentesis demonstrated higher success
      rate, fewer complications but slightly slower flow rate.

PMID- 21721442
TI  - Attainment of American Diabetes Association clinical practice recommendations in
      722 Thai type 2 diabetes patients.
AB  - BACKGROUND: Each year the American Diabetes Association (ADA) publishes the
      update clinical practice recommendation. However, the achievement of these
      practice recommendations remained suboptimal in several studies. The purpose of
      this study is to determine the degree diabetes patients achieved optimal clinical
      practice recommendations and to determine factors associated with reduced
      attainment of these recommendations in T2DM patient. MATERIAL AND METHOD: We
      conducted retrospective review medical records of Thai type 2 diabetes patients
      who were followed-up at out-patient department of internal medicine department,
      Siriraj hospital, Thailand, during January to December 2006. RESULTS: Of 722
      diabetes patients who were recruited, 64.5% and 60% had received HbA1c and plasma
      lipid profiles measurements, respectively, whereas blood pressure measurement was
      done in all patients. Forty-nine percent achieved the target HbA1c of less than
      7%, 64% achieved LDL-C and HDL-C targets and 58% achieved the triglycerides
      target, whereas only 31% of the patients achieved the BP target recommendation.
      Fifty-two percent of patients achieved at least 3 items according to ADA practice
      recommendation and 47.8% achieved only 0-2 items of clinical recommendation.
      Category of health care provider and elderly patients were independent factors
      for attainment of clinical practice recommendations. Moreover, patients who were
      diagnosed with diabetes for longer than 10 years and who used insulin treatment
      were independent factors for achieving good glycemic control. CONCLUSION: These
      data demonstrated a substantial proportion of diabetes patients did not achieve
      ADA clinical practice recommendations. This apparent gap was depended on
      categories of health care provider and patients' age. The novel and more
      effective strategies targeted these groups are needed to improve achievement of
      these recommendations.

PMID- 21721443
TI  - Assessment and prevalences of diabetic complications in 722 Thai type 2 diabetes
      patients.
AB  - BACKGROUND: The purpose of this study is to determine the percent of patients who
      have been assessed as having diabetic complications as recommended by American
      Diabetes Association. The secondary goals were to determine factor(s) associated
      with reduced assessment of diabetic complication and to determine the prevalence
      of diabetic complications in Thai type 2 diabetes patients. MATERIAL AND METHOD:
      We conducted a retrospective review of medical records of Thai type 2 diabetes
      patients who were followed up at the out-patient department (OPD) of Department
      of Internal Medicine at Siriraj Hospital Mahidol University Thailand during 1st
      January to 31st December 2006. RESULTS: Of 722 diabetes patients who were
      recruited, 7.5% were treated by general practitioners (GP), 10.4% by internal
      medicine residents (Res), 49.9% by internist (Int), 11.8% by endocrinologist
      (Endo) and 20.5% was indeterminate because they could not identify the field of
      the health care provider. 38.4% of patients received an eye examination by an
      ophthalmologist. 42% were screened for diabetic nephropathy. Serum creatinine
      level was measured in 83.5%. Foot examination was done in only 125 patients
      (17.3%). We founded that patients taken care by GP and Int received less
      intensive and less extensive assessment for diabetic complications than those
      taken care by Res and Endo. The prevalences of diabetic nephropathy and chronic
      kidney disease of at least stage 3 were 37 and 48.2%, respectively. Diabetic
      retinopathy occurred in 31.2%, cardiovascular disease in 28.9%, cerebrovascular
      disease in 10.6% and diabetic foot in 40%. CONCLUSION: There was a high
      prevalence rate of diabetic complications in patients with type 2 diabetes.
      Screening for diabetic complications will help to identify patients at high risk
      of concomitant complications eventhough some practitioners are not initially
      aware of the importance of the diabetic complication screening. These data may
      help the physician decide to modify treatment to prevent disabilities.

PMID- 21721444
TI  - Correlation of arterial, central venous and capillary lactate levels in septic
      shock patients.
AB  - BACKGROUND: Blood lactate level increases in response to tissue hypoxia and this
      level is currently used to monitor shock management. To obtain the arterial
      lactate value in clinical practice is a time consuming process. Our previous
      study demonstrated good correlation between the capillary lactate determined by a
      portable lactate analyzer and the standard arterial lactate in critically ill
      patients. This study was aimed to examine the uses of this capillary lactate in
      septic shock. MATERIAL AND METHOD: A prospective comparison of arterial, venous
      and capillary lactate level from septic shock patients admitted in the general
      wards and the Medical ICU, Department of Medicine, Siriraj hospital was performed
      during October 2009 to February 2010. RESULTS: Thirty patients were included in
      the study. The mean age was 66 (24-86) years and 16 (53%) were female. The
      correlation between arterial and central venous was 0.992 and the correlation
      between arterial and capillary lactate level was 0.945 (p = 0.01 in both
      comparisons). In addition, there was certain agreement between the arterial and
      the capillary lactate especially when arterial lactate was below 10 mmol/L.
      CONCLUSION: The capillary lactate level determined by the portable lactate
      analyzer (Accutrend Plus) correlated well with arterial lactate level. This
      method, when used cautiously, may be used to monitor septic shock treatment as an
      alternative to the standard arterial lactate determination.

PMID- 21721445
TI  - Evaluation of correlation between vascular pedicle width and intravascular volume
      status in Thai critically ill patients.
AB  - OBJECTIVE: To evaluate the correlation between vascular pedicle widths (VPW)
      measured from portable chest roentgenogram (CXR) and intravascular volume status
      in Thai critically ill patients. MATERIAL AND METHOD: A prospective cohort study
      included the critically ill patients in whom pulmonary artery catheter was placed
      in the Medical Intensive Care Units of Siriraj Hospital, Mahidol University
      between June 2009 and January 2010. The patient's baseline characteristics,
      hemodynamic data measured from pulmonary artery catheter (PAC) and CXR parameters
      were collected. RESULTS: From thirty-four patients, thirteen (38.2%) had high
      pulmonary artery occlusive pressure (PAOP > or =18 mmHg). The patients with high
      PAOP were older (69.8 +/- 8.8 years vs. 59.2 +/- 15.4 years, p = 0.02), taller
      (163.2 +/- 5.3 cm vs. 157.0 +/- 10.4 cm, p = 0.03) and higher weight (67.4 +/-
      12.9 kg vs. 57.1 +/- 7.8 kg, p = 0.007) than the low PAOP group. The correlations
      between PAOP and VPW (r = 0.68, p < 0.001) as well as between PAOP and
      cardiothoracic ratio (CTR) (r = 0.23, p = 0.03) were significant. From the
      receiver operating characteristic (ROC) curve, VPW > 68 mm is the best parameter
      to predict PAOP > or =18 mmHg (the area under the curve (AUC) = 0.853, p < 0.001,
      sensitivity = 92.3%, specificity = 85.7%). The CTR > 0.58 can be used to predict
      elevated PAOP > or =18 mmHg with acceptable sensitivity = 85.74% and specificity
      = 76.9% (AUC = 0.727, p = 0.03). The peribronchial cuffing (PBC) was detected at
      a higher percentage among high PAOP group than in the low PAOP group (76.9% vs.
      33.3%, p = 0.03). CONCLUSION: The VPW >68 mm, CTR >0.58 and the present of PBC
      can be used together to predict elevation of PAOP > or =18 mmHg among the Thai
      critically ill patients. By using these CXR parameters, the PAC insertion may be
      avoided especially in patients with contraindication.

PMID- 21721446
TI  - Right ventricular dysfunction in septic shock.
AB  - BACKGROUND: Right ventricular dysfunction (RVD) is common in critically ill
      patients and the presence of this condition affects patients' outcomes. Improving
      the knowledge background and establishing the incidence of RVD in septic shock
      patients would render the management more efficacious. This study was performed
      to evaluate the incidence and outcomes of RVD in septic shock patients. MATERIAL
      AND METHOD: A single center retrospective observational study was performed in
      the Medical ICU, Siriraj Hospital, Mahidol University between January 2007 and
      October 2009. Patients with septic shock in whom pulmonary artery catheter (PAC)
      was inserted were included in the study. RESULTS: The PAC was placed in 118
      patients during the study period. The patients' mean age was 58.0 +/- 18.5 years
      and 71 of them (59.3%) were male. The mean body mass index was 25.0 +/- 6.6 Kg/m2
      and the mean APACHE II score was 26.1 +/- 7.7. The admission diagnoses were
      severe sepsis or septic shock (70%), severe pneumonia (38%), acute respiratory
      distress syndrome (21%). Twenty one patients (17.8%) meet the diagnosis criteria
      of RVD. The hospital mortality in RVD patients tended to be higher than the non
      RVD patients (81.0% vs. 60.8%, p 0.06). Although similar proportions of both
      group received ventilatory support, the RVD patients had lower tidal volume and
      had higher peak airway pressure. Also the RVD group had lower PaO2/FiO2 ratio. In
      addition, the RVD group had lower cardiac output and more frequently underwent
      renal replacement therapy. CONCLUSION: In patients with septic shock, the
      incidence of RVD is substantial. The significant factors associated with RVD
      include low tidal volume and high peak airway pressure. Measures to prevent the
      alteration in lung compliance in septic shock patients may prevent RVD and
      improve patients' outcomes.

PMID- 21721447
TI  - Microbiological equivalence of bacteriostatic and bactericidal activities of the
      sera from healthy volunteers receiving generic piperacillin/tazobactam (Pipertaz)
      and original piperacillin/tazobactam (Tazocin).
AB  - BACKGROUND: Several generic piperacillin/ tazobactam formulations have been
      approved by Thai Food andDrugAdministration, Ministry of Public Health.
      Piperacillin/ tazobactam is a parenteral drug. Therefore, a study demonstrating a
      biological equivalence of generic piperacillin/ tazobactam is not required for
      drug registration in Thailand. OBJECTIVE: The study was to determine
      microbiological equivalence of serum bacteriostatic and bactericidal activities
      of the sera from healthy volunteers receiving generic piperacillin/ tazobactam
      (PipertazA) and original piperacillin/tazobactam (Tazocin). MATERIAL AND METHOD:
      This was a randomized crossover study in 16 adult healthy volunteers. Each
      subject received 4.5 grams of Pipertaz and Tazocin in 50 ml of normal saline via
      intravenous infusion for 30 minutes. The blood samples were drawn at baseline
      prior to receiving the study drug, at 30 minutes after initiating infusion, and
      at 8 hours after initiating infusion. The serum bacteriostatic activity against
      E. coli ATCC 25922, K. pneumoniae, P aeruginosa ATCC 27853 and A. baumannii was
      performed by disk diffusion The serum bactericidal activity against E. coli ATCC
      25922 was performed by Serum Bactericidal Titre. RESULTS: The average inhibition
      zone diameter of the serum samples from the subjects while receiving Pipertaz
      against each tested organisms was <1 mm smaller than that while receiving Tazocin
      and such difference was not significantly different. All serum samples collected
      at 30 minutes after initiating Tazocin and Pipertaz had bactericidal titres 1:64
      to 1:256 against E. coli ATCC 25922. All serum samples collected at 8 hours after
      initiating Tazocin and Pipertaz had bactericidal titres < 1:2 against E. coli
      ATCC 25922. The differences of serum bactericidal titres of the serum samples
      collected at 30 minutes (p = 0.7) and 8 hours (p = 1.0) after initiating Tazocin
      and Pipertaz were not statistically significant. CONCLUSION: The sera from
      healthy volunteers receiving Pipertaz contain bacteriostatic and bactericidal
      activities not significantly different from those receiving Tazocin.

PMID- 21721448
TI  - Performance of Leptospira immunoglobulin M ELISA and rapid immunoglobulin G
      immunochromatographic assays for the diagnosis of leptospirosis.
AB  - Using archived samples, we assessed the diagnostic capacity of two commercially
      available tests (an ELISA IgM and a rapid immunochromatographic test, ICT) for
      the detection of Leptospira spp. IgM and IgG antibodies to aid with the diagnosis
      of acute leptospirosis in febrile patients in Thailand. The sensitivities of the
      ELISA for the detection of IgM and the rapid immunochromatographic test for the
      detection of IgG were 60.7% (95% CI, 50.3 to 70.2%), and 83.2% (95% CI 73.9 to
      89.6%) respectively. False positive ICT result occurred in one patient with
      influenza B infection. The positive rates of both assays were high after the
      first week of onset of fever up to third weeks of illness.

PMID- 21721449
TI  - Epidemiology of suspected Clostridium difficile-associated hospital-acquired
      diarrhea in hospitalized patients at Siriraj Hospital.
AB  - BACKGROUND: Clostridium difficile-associated disease (CDAD) is an important cause
      of hospital-acquired diarrhea. OBJECTIVE: To determine the prevalence, risk
      factors, diagnosis, treatments and outcomes of the patients with CDAD in
      hospitalized patients at Siriraj Hospital. MATERIAL AND METHOD: The medical
      records of hospitalized patients aged older than 14 years who developed hospital
      acquired diarrhea and their stool samples were sent for detection of C. difficile
      toxins from March to June 2008 were reviewed. Risk factors of CDAD were
      identified by reviewing medical records of CDAD patients (case group) and
      patients who had hospital-acquired diarrhea without C. difficile toxins (control
      group). The patients in the control group were matched with the case group in
      terms of gender and age. RESULTS: Three hundred and twenty three stool samples
      obtained from 255 adult hospitalized patients were sent to microbiology
      laboratory for detection of C. difficile toxins. The prevalence of CDAD in
      suspected C. difficile-associated hospital-acquired diarrhea was 12.3% (95% CI
      8.5% to 17.6%). Univariate analysis showed that antibiotic use (> or =2 agents),
      proton pump inhibitor (PPI) use, hematologic malignancy, receiving chemotherapy
      or immunosuppressive agents were associated with CDAD. Multivariate analysis
      revealed that only antibiotic use (> or =2 agents), PPI use and hematologic
      malignancy were independent risk factors associated with CDAD. Nasogastric
      intubation was observed to be associated with CDAD as a protective factor from
      both univariate and multivariate analyses. Diagnosis of CDAD in most of the
      patients was made by a presence of C. difficile toxin in their stool samples.
      Response rate to metronidazole was 74.5%. The recurrence rate of CDAD was 3.2%.
      The mortality rate due to CDAD was 3.2%. CONCLUSION: CDAD is not uncommon in the
      patients with hospital-acquired diarrhea especially in those who have hematologic
      malignancy, receive multiple antibiotics or receive PPI. Metronidazole is an
      acceptable treatment for CDAD. The recurrence rate of CDAD and mortality rate due
      to CDAD are low.

PMID- 21721450
TI  - Monitoring of effectiveness and safety of generic formulation of meropenem for
      treatment of infections at Siriraj Hospital.
AB  - OBJECTIVE: In Siriraj Hospital, generic meropenem (Monem) has been available and
      was substituted for original meropenem, but the effectiveness and safety of using
      generic meropenem in a clinical setting are the main concern. MATERIAL AND
      METHOD: From July 2007 to June 2009, hospitalized patients aged 18 or older who
      received meropenem for 48 hours were identified from the pharmacy database of
      Siriraj hospital. A retrospective study was conducted. Three hundred patients in
      each of original and generic meropenem groups were required to demonstrate non
      inferiority of generic to original meropenem. RESULTS: The mean age of all
      patients was 63 years. Most of the patients had co-morbidities. Approximately 90%
      of the infections were health-care associated. Drug-resistant gram-negative
      bacteria including ESBL producing E. coli and K. pneumoniae, P. aeruginosa and A.
      baumannii account for nearly 50% of all organisms. No significant difference was
      found regarding characteristics, type or site of infection and pathogen between
      generic and original groups but for more patients in the original group having
      cardiovascular disease and more patients in the generic group receiving
      immunosuppressive agents. Eighty-two to 85% received meropenem with one of
      appropriate indications. No statistically significant difference occurred either
      in an overall favorable outcome (63% vs.70.4%, p = 0.07) or in overall mortality
      (38% vs. 32%, p = 0.17), as well as adverse effects between the original and the
      generic groups. CONCLUSION: Generic meropenem (Monem) was not inferior to
      original meropenem for therapy of infections in the hospitalized patients at
      Siriraj Hospital.

PMID- 21721451
TI  - The efficacy of 3-mg warfarin initiating dose in adult Thai patients, who
      required long-term anticoagulant therapy.
AB  - BACKGROUND: Warfarin anticoagulation is the standard treatment for patients with
      thromboembolic diseases. Prior studies recommended commencing warfarin with the
      initial doses between 5 mg and 10 mg for the first 1 or 2 days. However, lower
      warfarin loading dose is advised for the elderly and patients with co-morbid
      diseases. Moreover, warfarin requirement is also affected by several genetic
      factors, which differ among various ethnic populations. Currently, the optimal
      initiating dose of warfarin in Thai patients is unknown. However, based on the
      observation of the clinical practice at Siriraj hospital, a lower starting dose
      (3 mg/day) of warfarin was commonly given to patients who required long-term
      anticoagulant therapy. OBJECTIVE: To investigate the efficacy and safety of 3-mg
      warfarin initiating dose. MATERIAL AND METHOD: A retrospective study of
      inpatients who received warfarin 3 mg/day for the first two days of oral
      anticoagulation therapy with the target INR of 2.0-3.0 at Siriraj hospital from
      January 2004-December 2007 was performed. The efficacy of 3-mg warfarin loading
      dose was determined by assessing the proportion of patients who achieved the
      target INR of 2.0-3.0 between day 3 and day 5 of warfarin treatment. RESULTS:
      Total of 164 patients was included in the study. Eighty-six patients (52.4%) were
      males. The mean age was 55.1 + 16.8 years (range 16-88 years). The mean body
      weight and serum albumin were 61.5 +/- 12.2 kg and 3.7 +/- 0.7 g/dl,
      respectively. Prosthetic heart valve replacement was the most common indication
      for warfarin anticoagulation therapy (36%), followed by deep vein thrombosis
      (32.3%). The mean cumulative weekly dose of warfarin was 22.3 +/- 5.8 mg. The
      median time to therapeutic INR (2.0-3.0) was 6 days. Forty-seven patients (29%)
      achieved therapeutic INR between day 3 and day 5 of warfarin treatment. Time to
      therapeutic INR was not affected by age, gender, body weight, serum albumin, or
      concomitant medication use. Interestingly, patients who received warfarin due to
      prosthetic heart valve replacement were more likely to achieve therapeutic INR
      between day 3 and day 5 when compared to those with other indications with
      adjusted OR 16.25 (95% CI 5.13-51.44, p < 0.001). Bleeding complication was rare
      (0.6%) and was not associated with excessive anticoagulation. CONCLUSION: 3-mg
      warfarin initiating dose appeared to be safe in adult Thai patients. However, the
      efficacy of 3-mg starting dose as determined by the proportion of patients who
      achieved the target INR between day 3 and day 5 of warfarin treatment was
      relatively less efficient when compared with that previously reported with a 5-mg
      loading dose. Further randomized, prospective study is required to examine the
      efficacy of 3-mg versus higher warfarin starting dose in Thai patients.

PMID- 21721452
TI  - Utilization of a scoring system for diagnosis of chronic lymphocytic leukemia in
      Thai patients.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is a rare B-lymphoid malignancy in
      Southeast Asia. We evaluated whether a scoring system based on the expression of
      CDS, CD23, FMC7, CD79b and surface immunoglobulin (Slg) could be utilized to
      distinguish CLL from other types of lymphoid neoplasms in the Thais. MATERIAL AND
      METHOD: One-hundred and forty-five samples with a clinical suspicion for CLL were
      analysed by flow cytometry. A score of one was assigned if the following marker
      was identified: CD5+, CD23+, FMC7-, CD79b- and SIg(-/weak). A cut-off score of >
      or =3 was required for the definitive diagnosis of B-CLL. RESULTS: Only 50 cases
      (34.5%) were confirmed as B-CLL (scores > or =3). Cases with scores > or =3 had
      significantly higher leukocyte counts and marrow/blood lymphocytes than cases
      with scores < or =2. Dual CD5/CD23 expression was found in 87.5% of CLL cases. In
      81 cases with scores < or =2, a variety of non-CLL disorders predominated, such
      as marginal zone lymphoma, splenic lymphoma with villous lymphocytes, mantle cell
      lymphoma, and prolymphocytic leukemia. CONCLUSION: A score of 3 and dual CD5/CD23
      expression are essential for the diagnosis of CLL while a score of 2 mostly
      indicative of non-CLL. The majority of clinical cases of CLL turned out to be non
      CLL by flow cytometry. Increased utilization of this scoring system should
      increase the accuracy of diagnosis of this rare type of leukemia in the Thai
      population.

PMID- 21721453
TI  - Incidence and risk factors of bone marrow involvement by non-Hodgkin lymphoma.
AB  - BACKGROUND: Since trephine bone marrow biopsy is an invasive procedure, the
      identification of a subgroup of patients with Non-Hodgkin lymphoma (NHL) who have
      a minimal risk of bone marrow involvement would be helpful. This study is aimed
      to determine the incidence of bone marrow involvement (BMI) by NHL and the
      predictors of no BMI to not only avoid this invasive procedure but also decrease
      the cost of investigation. MATERIAL AND METHOD: Data from 320 patients with NHL
      at division of hematology between January 2008 and June 2009 were reviewed and
      analyzed. RESULTS: The cell types of NHL were classified as B-cell in 283
      patients (88.4%), T-cell in 37 patients (11.6%) and incidence of BMI is 24.4% and
      18.9% in B- and T-cell, respectively. Factors significantly associated with BMI
      in univariate analysis were the hepatic and splenic involvement (p = 0.03 and <
      0.01, respectively), significant weight loss (p = 0.02), presence of
      lymphadenopathy (LN) below diaphragm (p = 0.02), anemia (p = 0.001), low percent
      of blood neutrophil (p < 0.001), high percent of blood lymphocyte (p < 0.001),
      low absolute neutrophil count (p = 0.002), high absolute lymphocyte count (p =
      0.045), low platelet count (p < 0.001), high LDH (p = 0.026), and high alkaline
      phosphatase (p = 0.020). On the multivariate analysis, factors associated with
      BMI included LN below diaphragm, anemia, low percent of blood neutrophil and low
      platelet count. Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients
      with no LN below diaphragm, no hepatic & splenic involvement, no significant
      weight loss, hemoglobin (Hb) >11 g/dL and platelet > 150,000/uL had BMI in 3/78
      (3.8%). CONCLUSION: The incidence of bone marrow involvement in NHL is 23.8%.
      Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients with no LN
      below diaphragm, no hepatic & splenic involvement, no significant weight loss, Hb
      > 11 g/dL and platelet > 150,000/uL had low risk of BMI.

PMID- 21721454
TI  - Can we predict final outcome of internal medicine residents with in-training
      evaluation.
AB  - OBJECTIVE: To assess the predictive value of in-training evaluation for
      determining future success in the internal medicine board certifying examination.
      MATERIAL AND METHOD: Ninety-seven internal medicine residents from Faculty of
      Medicine Siriraj Hospital who undertake the Thai Board examination during the
      academic year 2006-2008 were enrolled. Correlation between the scores during
      internal medicine rotation and final scores in board examination were then
      examined. RESULTS: Significant positive linear correlation was found between
      scores from both written and clinical parts of board certifying examination and
      scores from the first-year summative written and clinical examinations and also
      the second-year formative written examination (r = 0.43-0.68, p < 0.001). Monthly
      evaluation by attending staffs was less well correlated (r = 0.29-0.36) and the
      evaluation by nurses or medical students demonstrated inverse relationship (r = 
      0.2, p = 0.27 and r = -0.13, p = 0.48). CONCLUSION: Some methods of in-training
      evaluation can predict successful outcome of board certifying examination.
      Multisource assessments cannot well extrapolate some aspects of professional
      competences and qualities.

PMID- 21721455
TI  - Unusual presentation as an adult onset painful myopathy in a Thai patient with
      Becker muscular dystrophy.
AB  - A Thai 37-years-old man presented with adult onset progressive proximal muscle
      weakness and generalized myalgia. Family history showed similar symptoms in
      several male relatives, compatible with X-linked recessive inheritance.
      Electromyography suggested myopathic process. Serum creatine kinase was highly
      elevated. Diagnosis of Becker muscular dystrophy (BMD) was confirmed by genetic
      testing. His symptoms responded well to steroid treatment. This report is of the
      first Thai patient with atypical presentation of BMD.

PMID- 21721456
TI  - Pancreatic panniculitis: a cutaneous presentation as an initial clue to the
      diagnosis of pancreatic cancer.
AB  - BACKGROUND: Pancreatic panniculitis is a rare complication of pancreatic
      diseases, including pancreatic carcinoma. It is clinically manifested by
      erythematous subcutaneous nodules typically located on the legs which can occur
      before or at the onset of pancreatic disease. CASE REPORT: An 81-year-old woman
      presented with painful subcutaneous nodules at both shins, recurrent epigastric
      pain, anorexia and significant weight loss. Physical examination revealed mild
      pallor, palpable epigastric mass and multiple tender erythematous subcutaneous
      nodules discrete to both lower extremities. The skin biopsy showed lobular
      panniculitis with marked subcutaneous fat necrosis and ghost adipocytes
      compatible with pancreatic panniculitis that was an important clue for further
      investigations. Elevations of serum amylase and serum lipase were then noted.
      Computed tomography of the abdomen revealed pancreatic cancer with duodenal
      involvement and multiple liver metastases. CONCLUSION: Pancreatic panniculitis is
      associated with pancreatic cancer and represents an important clue to the
      diagnosis.

PMID- 21721457
TI  - Inadvertent intrathecal vincristine administration: report of a fatal case
      despite cerebrospinal fluid lavage and a review of the literature.
AB  - Accidental intrathecal vincristine administration results in progressive
      ascending radiculomyeloencephalopathy usually leading to fatal outcome. No
      specific therapy for intrathecal vincristine toxicity has been reported. We
      report a 63-year-old man with diffuse large B-cell lymphoma at the right testis
      who inadvertently received intrathecal vincristine. Direct CSF aspiration and
      irrigation was done 30 minutes after the incident. Ventriculostomy and lumbar
      drain was placed. Intrathecal irrigation was started at 6.5 hours using FFP
      containing lactate solution and continued for 11 days. In addition,
      antineurotoxic and neuroprotective agents were given. His neurological symptom
      deteriorated slowly and he died on day 12. Among 16 reported cases undergoing
      lumbar drainage and/or irrigation, 56.3% can survive 30 days or more and 37.5%
      had survive more than 6 months. Immediate CSF drainage and early irrigation is
      related to good outcome (prolonged survival with no encephalopathy). In our case,
      his poor outcome might be due to the delayed starting of irrigation. In
      conclusion, the appropriate and effective management of this complication is
      unknown. However, emergency cerebrospinal fluid drainage and irrigation remains
      the principal of management.

PMID- 21721458
TI  - Patent foramen ovale and recurrent transient neurological symptoms: a case report
      and review of literature.
AB  - Stroke is a common cause of morbidity and mortality in adults worldwide. Because
      patent foramen ovale (PFO) is commonly found in normal population, we need to
      identify a subset of cryptogenic stroke patients who are likely to have
      experienced paradoxical embolization. Various factors need to be considered such
      as atrial anatomic variation (PFO size, atrial septal aneurysm, eustachian valve
      anatomy), hemodynamic parameters, presence of venous thrombosis and presence
      ofhypercoagulable state. The presence of any of these findings increase the
      chance of PFO contributing to stroke. We describe a 54-year-old patient with a
      history of well controlled hypertension and dyslipidemia who presented with 3
      attacks of expressive aphasia lasting 5 minutes each. General medical and
      neurological examinations were normal. Transesophageal echocardiography with
      agitated saline injection revealed presence of PFO flap. Transcranial Doppler
      ultrasonography with three agitated saline injections showed multiple unilateral
      microembolism signals in the M1 of left middle cerebral artery. Aspirin was given
      as well as percutaneous endovascular PFO closure was performed with no immediate
      complication. Patient has had no further attack of stroke after 6 months follow
      up.

PMID- 21721459
TI  - The possible role of adrenomedullin in the etiology of gestational hypertension
      and preeclampsia.
AB  - INTRODUCTION: Nowadays the possible role of vasoactive peptide adrenomedullin
      (ADM) is considered in the etiology of preeclampsia (PE), where ADM is indicated
      to be a protective factor decreasing blood pressure. The aim of this study was to
      evaluate the role of -1984A>G ADM gene polymorphism and its connection with ADM
      plasma level in women with gestational hypertension (GH) and preeclampsia.
      MATERIAL AND METHODS: 63 hypertensive (30 with GH and 33 with PE) and 94 healthy
      pregnant women were included into the study The frequency of genotypes and
      alleles of -1984A>G ADM gene polymorphism was examined by PCR/RFLP method. ADM
      concentration was measured by ELISA method. RESULTS: In GH subgroup higher
      frequency of heterozygous AG genotype (16.67% vs. 8.50%, O.R. = 2.68, p = ns) and
      G allele (11.67 vs. 4.30%, O.R. = 2.97, p = 0.043) was observed. In PE subgroup
      overrepresentation of heterozygous AG genotype (15.15% vs. 8.5%) and slightly
      higher frequency of G allele (p = ns) were noted. In AA genotype subgroup of
      hypertensive women in comparison to the AG+GG genotype group higher proteinuria
      value (212.1 vs. 90.9 mg/dl, p < 0.0001), lower systolic (171.1 vs. 177.3 mmHg),
      as well as lower diastolic blood pressure level (107.1 vs. 111.4 mmHg) were
      noted. The highest ADM plasma level was observed in the group of women with PE
      (1.817 vs. 1.692 ng/ml, p = ns). Moreover, higher ADM plasma concentration in
      patients with AA genotypes in comparison to the carriers of AG and GG genotypes
      (1.844 vs. 1.402 ng/ml, p = ns) was noted. CONCLUSIONS: Higher ADM plasma
      concentration in women with PE suggests possible correlation between ADM level
      and pathological changes in cardiovascular system during pregnancy
      Overrepresentation of genotypes containing at least one mutated G allele of the 
      1984A>G ADM gene polymorphism in women with GH and PE suggests participation of
      this allele in pathogenesis of these conditions. Higher ADM concentration in
      carriers of homozygous AA genotype found in GH and PE groups indicates the
      possible important role of A allele in prevention of GH/PE appearance.

PMID- 21721460
TI  - Cyclopia--literature review and a case report.
AB  - Cyclopia is a deformation of the facial skeleton with one eye orbit formed in the
      place where both eyes should be present. As a result of hypoplasia there is
      absence (hypothesized loss) of central nervous system structures. Teratogenic
      factors leading to the occurrence of this anomaly may include irregular
      cholesterol biosynthesis, viruses, alcohol intake and maternal diabetes. Many
      authors suggest genetic etiology of this illness. The following work presents a
      case of a female patient whose fetus was diagnosed with multiple defects, among
      others with cyclopia. After pharmacological induction of labor, a male fetus with
      vital signs was born but died after two hours. As far as cyclopia is concerned,
      special attention should be paid to proper diagnosis of this pathology at an
      earliest possible stage of fetal life. Early ultrasound diagnostics of this
      anomaly must be emphasized most strongly leading to the conclusion that patients
      suspected of fetal facial skeleton defects should be referred to medical centers
      which are qualified in prenatal examinations.

PMID- 21721461
TI  - Brucellosis in adolescent pregnancy--case report and review of literature.
AB  - Brucellosis is a zoonotic disease that can be encountered during pregnancy
      especially in endemic areas such as Latin America, Africa, Asia, Mediterranean
      countries and eastern region of Turkey. We present a case of a 19-year-old
      pregnant woman of 19-20 weeks gestation diagnosed with brucellosis. Main
      presentation at admission were hematuria and nausea. Advanced investigations
      revealed blood culture positive for brucella. Abortion occurred in the course of
      medical therapy.

PMID- 21721462
TI  - The somatotropic axis in postmenopausal women during six month of transdermal
      continuous 17beta-estradiol administration combined with oral
      medroxyprogesterone.
AB  - AIM: The evaluation of the influence of continuous transdermal estradiol
      supplementation combined with oral medroxyprogesterone on the somatotropic axis
      in postmenopausal women. MATERIAL AND METHODS: 25 women completed the study Group
      A--13 women received transdermal 17beta-estradiol (Oesclim 50 - Fournier-Solvay)
      combined with oral 5 mg daily medroxyprogesterone (Gestomikron - Adamed). Group B
      -12 women without treatment. Basic plasma FSH, estradiol, glucose, insulin, SHBG,
      hGH, total and free IGF-I, IGFBP-1 as well as IGFBP-3 were measured initially and
      at the 12th and 24th week of the study. RESULTS: The mean plasma FSH level was
      reduced and mean plasma estradiol level was increased in group A during estradiol
      supplementation. Mean plasma level of free IGF-I and free to total IGF-I ratio
      were increased in group A during 24 weeks of hormone therapy. In the control
      group (group B) there was the significant increase in mean plasma IGFBP-3 level.
      Other parameters showed no significant changes in the control group. CONCLUSION:
      The administration of transdermal 17beta-estradiol combined with oral
      medroxyprogesterone increases the IGF-I bioavailability. However this influence
      do not exceed the physiologial level of IGF-I bioavailability.

PMID- 21721463
TI  - Evaluation of the relationship between insulin resistance and recurrent pregnancy
      loss.
AB  - OBJECTIVE: To investigate insulin resistance in patients with recurrent pregnancy
      loss (RPL). DESIGN: Single center, case-control, prospective study. METHODS: The
      study was performed at the Obstetrics and Gynecology Clinic at the Dicle
      University Medical Faculty from May to October 2009. 64 study subjects who had
      RPL were compared to 64 controls. Both groups were compared with fasting glucose,
      fasting insulin, fasting glucose/fasting insulin, and homeostasis model
      assessment of insulin resistance (HOMA-IR) index values to assess insulin
      resistance. RESULTS: No significant differences in age and BMI index were found
      between the study and control subjects (p > 0.005). The mean number of abortions
      was 3.04 in the study and 0.2 in the control group (p < 0.001). The mean fasting
      glucose value was 100.84 in the study group, and 89.67 in the control group (p <
      0.001). Also, the mean fasting insulin value was 15.51 in the study group and
      7.17 in the control group (p = 0.001). The mean glucose/ insulin ratio was 12.24
      in the study group and 28.27 in the control group (p = 0.017), and the mean HOMA
      IR value was 4.16 in the study group and 1.62 in the control group (p = 0.002).
      CONCLUSION: Compared with the control group, patients with RPL were more likely
      to have insulin resistance.

PMID- 21721464
TI  - Tubal torsion during pregnancy--case report.
AB  - Tubal torsion is a very rare event, especially in pregnancy. We present a case of
      a patient of 20 weeks gestation that was admitted to our clinic with acute
      abdomen. Radiological and biochemical investigations did not reveal the cause of
      abdominal pain which resulted in laparatomic exploration. During the operation,
      the paratubal cystic mass, previously explored by ultrasonographic examination,
      and the left fallopian tube were found twisted among themselves. Salpingectomy
      was performed due to the necrotic appearance of the fallopian tube.

PMID- 21721465
TI  - A message from the President of IMPI.

PMID- 21721466
TI  - High power limits of waveguide stub tuners.
AB  - Three effects limiting power handling capacity of a 2.45-GHz R-26 waveguide stub
      tuner have been investigated by means of electromagnetic simulation and partly by
      experiments: electric breakdown, microwave power dissipation in tuning stubs, and
      leakage of microwave radiation to environment. Critical situation in terms of
      load reflection coefficient has been identified. A tuner working chart is
      proposed which, for a given stub design, relates the highest tolerable microwave
      power for arc-free operation to maximum allowable load reflection coefficient. It
      is shown that high-reflection loads can increase noncontacting stub leakage
      levels by more than 10 dB, which should be considered in choke design. The
      described methodology can be applied to any type of waveguide and tuning stub
      structure.

PMID- 21721467
TI  - Numerical modeling of continuous flow microwave heating: a critical comparison of
      COMSOL and ANSYS.
AB  - Numerical models were developed to simulate temperature profiles in Newtonian
      fluids during continuous flow microwave heating by one way coupling
      electromagnetism, fluid flow, and heat transport in ANSYS 8.0 and COMSOL
      Multiphysics v3.4. Comparison of the results from the COMSOL model with the
      results from a pre-developed and validated ANSYS model ensured accuracy of the
      COMSOL model. Prediction of power Loss by both models was in close agreement (5
      13% variation) and the predicted temperature profiles were similar. COMSOL
      provided a flexible model setup whereas ANSYS required coupling incompatible
      elements to transfer load between electromagnetic, fluid flow, and heat transport
      modules. Overall, both software packages provided the ability to solve
      multiphysics phenomena accurately.

PMID- 21721468
TI  - Effect of particle size and relative density on powdery Fe3O4 microwave heating.
AB  - In recent years, microwave energy is expected to be a heat source of high
      temperature process aiming for CO2 reduction and energy conservation owing to the
      possibility of volumetric heating. In order to examine the applicability of
      microwave heating to ironmaking, it is important to investigate the microwave
      heating of raw materials of ironmaking such as Fe3O4. In this study, the effect
      of particle size and relative density on microwave absorptivity of powdery Fe3O4
      was elucidated by the heating curves. Powdery Fe3O4 samples having different
      particle sizes and relative densities and bulk Fe3O4 samples were heated at the
      positions of the H (magnetic) and E (electric) field maxima in a 2.45 GHz single
      mode microwave cavity. Sample temperatures abruptly increase and become constant
      after a while. At a constant temperature, the energy balance is attained, i.e.,
      the rate of microwave energy absorption is equal to the rate of thermal energy
      dissipation. Assuming that the thermal energy dissipation rate due to convection
      and radiation heat fluxes is only a function of the sample temperature, the
      microwave absorptivity could be evaluated by the temperature at the steady state.
      It has been found that the microwave absorptivity of Fe3O4 powder decreases with
      an increase in relative density. On the other hand, the microwave absorptivity
      hardly depends on the particle size, which may be due to its quite a large
      penetration depth of Fe3O4 compared to metal.

PMID- 21721469
TI  - Microwave synthesis of cyanine dyes.
AB  - Heptamethine cyanine dyes are a class of near infrared (NIR) dyes that have
      captured the interest of the scientific community. Although applications that
      utilize NIR fluorescence technology are rapidly expanding, progress is limited by
      the lack of availability and cost of suitable compounds that can be utilized as
      labels and/or probes. Herein, we report the use of microwave assisted organic
      synthesis of five NIR cyanine dyes in yields ranging from 64-83% with a
      significant reduction in solvent use. Spectra characteristics including
      absorbance and emission spectra, molar absorptivity, quantum yield, fluorescence
      lifetime, and redox potentials were determined for each synthesized NIR cyanine
      dye.

PMID- 21721470
TI  - Utilization of microwave energy for decontamination of oil polluted soils.
AB  - Soil oil (petroleum) product pollution represents a great environmental threat as
      it may contaminate the neighboring soils and surface and underground water.
      Liquid fuel contamination may occur anywhere during oil (petroleum) product
      transportation, storing, handling and utilization. The polluted soil recovery
      represents a complex process due to the wide range of physical, chemical and
      biological properties of soils which should be analyzed in connection with the
      study of the contaminated soil behavior under the microwave field action. The
      soil, like any other non-metallic material, can be heated through microwave
      energy absorption due to the dielectric losses, expressed by its dielectric
      complex constant. Oil polluted soil behaves differently in a microwave field
      depending on the nature, structure and amount of the polluting fuel.
      Decontamination is performed through volatilization and retrieval of organic
      contaminant volatile components. After decontamination only a soil fixed residue
      remains, which cannot penetrate the underground anymore. In carrying out the soil
      recovery process by means of this technology we should also consider the soil
      characteristics such as: the soil type, temperature, moisture.The first part of
      the paper presents the theoretical aspects relating to the behavior of the
      polluted soil samples in the microwave field, as well as their relating
      experimental data. The experimental data resulting from the analysis of soils
      with a different level of pollution point out that the degree of pollutant
      recovery is high, contributing to changing the initial classification of soils
      from the point of view of pollution. The paper graphically presents the levels of
      microwave generated and absorbed power in soil samples, soil temperature during
      experimentations, specific processing parameters in a microwave field. It also
      presents the constructive solution of the microwave equipment designed for the
      contaminated soil in situ treatment.

PMID- 21721471
TI  - MICRA managing.

PMID- 21721472
TI  - Spotlight, dog in the practice are 'unacceptable'.

PMID- 21721473
TI  - Campaign under way for tobacco-free baseball in major league parks.

PMID- 21721474
TI  - Fracture strength in restored teeth before and after load cycling: an in vitro
      study.
AB  - This study compares the fracture resistance of endodontically treated teeth
      before and after load cycling. Forty-two maxillary incisors were selected. In
      groups 1 and 2, casting post and core was used. In groups 3 and 4, Dentatus posts
      and composite were used, and in groups 5 and 6, FRC posts were used. The load
      cycling had no statistically significant effect on fracture strength among
      groups.

PMID- 21721475
TI  - Effects of nutritional supplementation on periodontal parameters, carotenoid
      antioxidant levels, and serum C-reactive protein.
AB  - Few studies have focused on the role of nutrition in periodontal disease. The
      purpose of this trial was to determine the effect of a nutritional supplement on
      gingival inflammation, bleeding, probing depth, clinical attachment level,
      carotenoid antioxidant level, and C-reactive protein. The test supplement,
      consisting of a standard multivitamin formula, as well as several phytonutrients
      associated with antiinflammatory/antioxidant effects, provided modest benefits in
      reducing inflammation; however, further studies with larger populations and
      longer intervention are warranted.

PMID- 21721476
TI  - Molecular regulatory mechanism of root development.
AB  - TGF-beta signaling is known to function during tooth formation. The authors'
      study investigated the role of TGF-beta signaling during tooth root development
      and determined how the common mediator for TGF-beta signaling, Smad4, affected
      root formation in mice. Smod4 was specifically inactivated in all epidermal
      derived tissues by using a two-component genetic system. The authors' findings
      show that when Smad4 expression is eliminated in the dental epithelium, there is
      lack of root formation and severe crown defects.

PMID- 21721477
TI  - Velopharyngeal, speech and dental characteristics as diagnostic aids in 22q11.2
      deletion syndrome.
AB  - This study examines velopharyngeal, speech, and dental parameters as possible
      diagnostic aids in 22q11.2 deletion syndrome. It is a retrospective study on 56
      individuals. Twenty-one percent had a submucous cleft palate and 41 percent
      required palate surgery for speech. Common dental findings included poor oral
      hygiene, multiple carious lesions, congenitally missing teeth, class II
      malocclusion, and open bite.There are common findings that can aid the dental
      practitioner in recognizingthe syndrome and make appropriate referrals.

PMID- 21721478
TI  - A rich history and a bright future.

PMID- 21721479
TI  - Beginning the school year with novel H1N1: where are we now?

PMID- 21721480
TI  - Promoting school nursing: the role of school nurse educators.

PMID- 21721481
TI  - Why conduct an assessment of a school nurse program!

PMID- 21721482
TI  - When your child is diagnosed with diabetes: parents' questions for the health
      care team.

PMID- 21721483
TI  - Successful legislative efforts in Oregon: passage of House Bill OR. 2693 (2009).

PMID- 21721484
TI  - What is social media and what can it do for me?

PMID- 21721485
TI  - Advocacy goals: getting from point A to point B.

PMID- 21721486
TI  - A story to tell: advocacy as an association leader.

PMID- 21721487
TI  - National Commission on Children and Disasters urges Obama Administration and
      Congress to address unique disaster needs of children.

PMID- 21721488
TI  - How to achieve healthy school environments.

PMID- 21721489
TI  - Ridding schools of junk food.

PMID- 21721490
TI  - The challenge of diabetes: a parent's perspective.

PMID- 21721491
TI  - Tar Heel footprints in health care: Katherine Shea, MD, MPH.

PMID- 21721492
TI  - Barriers to municipal planning for pedestrians and bicyclists in North Carolina.
AB  - BACKGROUND: The Guide to Community Preventive Services recommends implementing
      community- and street-scale urban design, as well as land use policies and
      practices, to promote walking and bicycling. To better understand barriers to
      municipal walking and bicycling projects and policies, we surveyed municipal
      staff in North Carolina. METHODS: We surveyed all 121 municipalities with at
      least 5,000 persons, and 62% responded. We also surveyed 216 of 420
      municipalities with less than 5,000 persons, and 50% responded. The municipal
      staff member most knowledgeable about walking and bicycling planning was asked to
      complete the survey. Responses were weighted to account for the sampling design,
      to reflect prevalence estimates for all North Carolina municipalities. RESULTS:
      Common barriers to walking and bicycling projects and policies were selected from
      a 14-item list. For walking, barriers included lack of funding (93% of responding
      municipalities), other infrastructure priorities (79%), automobile infrastructure
      priorities (66%), and staffing challenges (65%). For bicycling, barriers included
      lack of funding (94% of responding municipalities), other infrastructure
      priorities (79%), automobile infrastructure priorities (73%), issues were not
      high priorities for the municipality (68%), staffing challenges (68%), and
      insufficient support from residents (63%). Barriers generally were more prevalent
      among rural municipalities than among urban municipalities (9 of 14 barriers for
      walking and 5 of 14 for bicycling; P < .10). LIMITATIONS: The study relied on 1
      respondent to report for a municipality. Additionally, job titles of respondents
      varied with municipality size. CONCLUSIONS: Health professionals and
      multidisciplinary partners can assist in overcoming the common local- and state
      level barriers to walking and bicycle projects and policies that are reported by
      North Carolina municipalities.

PMID- 21721493
TI  - Suitability of public records for evaluating health effects of treated sewage
      sludge in North Carolina.
AB  - BACKGROUND: Exposure to potentially harmful agents because of waste disposal
      practices is receiving increased attention. Treated sewage sludge (TSS), or
      biosolid material, is the solid waste generated during domestic sewage treatment
      after it has undergone processes to reduce the number of pathogens and vector
      attractants. Application of TSS to land, which is the most common method for
      disposal, is promoted as a soil amendment and fertilizer. Few studies have
      examined the effects of land application on the health and quality of life of
      neighboring populations. We describe and summarize publicly available records
      that could be used to study the public health impact of practices associated with
      land application in North Carolina. METHODS: We abstracted public records from
      the North Carolina Department of Natural Resources Division of Water Quality, to
      determine the following activities associated with land application of TSS in 8
      counties in central North Carolina: the process for obtaining permits, reported
      applications, violations, documented concerns of residents, and penalties
      assessed. RESULTS: The Division of Water Quality routinely collects records of
      permits and approvals for land application of TSS, amounts applied, and reported
      pollutant levels. Documentation was useful in summarizing land application
      practices, but lack of standardization in reporting was a concern. Research into
      the public health impacts of the land application program is hindered by
      inconsistency in documenting inspections and resident concerns. LIMITATIONS: We
      were not able to validate state records with direct observation of land
      application of TSS. CONCLUSIONS: Records from the Division of Water Quality would
      be of limited use in epidemiologic studies of the health effects of land
      application of biosolids. Information about locations, amounts, and dates of
      application are relevant to exposure potential, but additional information is
      needed for health investigations.

PMID- 21721494
TI  - Quality of pulmonary function testing in 3 large primary care pediatric clinics
      in rural North Carolina.
AB  - BACKGROUND: Pulmonary function testing (eg, spirometry) is recommended by the
      National Heart, Lung, and Blood Institute as part of basic asthma management.
      Previous research has shown that spirometry is feasible in primary care settings.
      OBJECTIVES: In this retrospective study, we sought to describe the proportion of
      spirometries meeting American Thoracic Society (ATS) and European Respiratory
      Society (ERS) quality criteria in children with asthma evaluated in North
      Carolina primary care pediatric clinics and to characterize predictors of
      spirometry that meets ATS/ERS quality criteria. METHODS: Medical records and
      spirometries from January 1, 2001, to August 1, 2009, were reviewed and analyzed
      from children enrolled in a larger asthma study that focused on communication
      between physicians, children, and caregivers. Children were eligible for the
      larger study if they were between the ages of 8 and 16 years and had received a
      previous diagnosis of persistent asthma. Children were enrolled from primary care
      pediatric practices. RESULTS: Spirometry was not acceptable, on the basis of
      ATS/ERS criteria, in 75% of cases. Approximately 19% of spirometries used
      incorrect or outdated predictive sets. CONCLUSIONS: More than three-quarters of
      spirometries in these primary care pediatric clinics were unacceptable. Changes
      or lack of changes in asthma management may be based on unacceptable spirometry.
      Additional education and training regarding accurate spirometry and
      interpretation are warranted.

PMID- 21721495
TI  - Improving asthma care in emergency departments: results of a multihospital
      collaborative quality initiative in rural western North Carolina.
AB  - BACKGROUND: In North Carolina, nearly one-fourth of persons with asthma visit an
      emergency department (ED) or urgent care center at least once a year because of
      an exacerbation of asthma symptoms. The Emergency Department Asthma Program was a
      quality-improvement initiative designed to better understand the population of
      patients who use the ED for asthma care in rural western North Carolina and to
      demonstrate whether EDs at small hospitals could, by implementing National Asthma
      Education and Prevention Program treatment guidelines, improve asthma care and
      reduce subsequent asthma-related ED visits. METHODS: Eight hospitals in western
      North Carolina participated in the project, which lasted from November 2003
      through December 2007. The intervention consisted of a series of individual and
      structured continuing medical education events directed at ED physicians and
      staff. Additionally, patients presenting to EDs for asthma-related problems were
      selected to receive a short patient questionnaire, to determine their basic
      understanding of asthma and barriers to asthma care; to undergo asthma staging by
      the treating physician; to receive focused bedside asthma education by a
      respiratory therapist; and, finally, at the treating physician's discretion, to
      receive a free packet of asthma medications, including rescue therapy with a beta
      agonist and corticosteroid therapy delivered via a metered-dose inhaler, before
      discharge. RESULTS: During the 37-month project, a total of 1,739 patients
      presented to the participating EDs for 2,481 asthma-related episodes of care; at
      11% of these visits, patients received the intervention, with nearly 100 ED
      physicians referring patients to the program. Most of the patients using the ED
      for asthma treatment were judged to have the mildest stages, and nearly half were
      uninsured or were covered by Medicaid. For only 20% of the visits was a primary
      care physician or practice identified. The patient intervention did not appear to
      lessen the rate of return visits for asthma-related symptoms at 30 and 60 days.
      LIMITATIONS: Selection bias is likely, as patients enrolled in the study were
      more likely than patients in the target sample to be adults and insured. Because
      we did not measure ED staff attendance at educational sessions or their knowledge
      of and attitudes about asthma care before and after the educational program, we
      cannot draw conclusions about the effectiveness of the program to change their
      knowledge, attitudes, or behavior. CONCLUSIONS: Many patients who use the ED for
      care appear to have mild, intermittent asthma and do not identify a regular
      source of primary care. Efforts to improve asthma care on a communitywide basis
      and to reduce preventable exacerbations should include care provided in EDs, as
      this may be the only source of asthma care for many asthma patients. The project
      demonstrated that regional, collaborative performance improvement efforts in EDs
      are possible but that many barriers exist to this approach.

PMID- 21721496
TI  - Public health and environmental health. Introduction.

PMID- 21721497
TI  - Reducing North Carolina's health care costs through environmental disease
      prevention.
AB  - At a time of unprecedented pressure on the North Carolina state budget, reducing
      environmental risks to health may provide opportunities for substantial savings
      in the proportion of the state budget (24%) that is allocated for medical
      assistance. Recently, the Research Triangle Environmental Health Collaborative
      held a summit to identify options for increasing attention to environmental
      impacts on health in the ongoing health care and budget debates. Summit
      participants included not only public health and environmental experts, but also
      individuals (such as transportation planners, developers, and industry
      representatives) whose decisions can have a significant impact on environmental
      quality. This article summarizes key recommendations from the summit, as well as
      commentaries in the policy forum of this issue that further elaborate on why
      environmental quality matters for public health in North Carolina. Key
      recommendations from the summit include requiring formal health impact
      assessments (similar to environmental impact assessments but with an emphasis on
      health) in state and local transportation and land use planning processes,
      quantifying the total disease burden attributable to environmental hazards in
      North Carolina, prioritizing environmental risks to health in North Carolina,
      providing state technical assistance for communities disproportionately affected
      by poor environmental quality, establishing a new database system to link
      existing environmental and public health data by geographic location, undertaking
      North Carolina case studies to test the hypothesis that improving environmental
      quality also reduces medical care costs, and developing "environment matters to
      your health" public awareness campaigns.

PMID- 21721498
TI  - Neighborhood-specific epigenome analysis: the pathway forward to understanding
      gene-environment interactions.
AB  - Morbidity and mortality associated with complex diseases are expected to increase
      as the population ages and the number of Americans living in poverty continues to
      expand. Therefore, improved translation of research findings into clinical
      practice and public health policy must become a priority. This commentary
      emphasizes the need for a new research model that accommodates the complex nature
      of disease etiology.

PMID- 21721499
TI  - The North Carolina Clean Smokestacks Act.
AB  - The story of North Carolina's Clean Smokestacks Act is a story about the link
      between the environment and health. It is a story about the good things that can
      happen when a state looks at health care policy through the lens of environmental
      health. For North Carolina, those good things are cleaner air and better health,
      for people and the environment, from Clingman's Dome to Jockey's Ridge.

PMID- 21721500
TI  - Use of spatial analysis to support environmental health research and practice.
AB  - Recent advances in spatial statistics and geographic information systems provide
      innovative platforms for diagnosing environmental health problems and for
      developing interventions. This article discusses when and where spatial
      techniques can most effectively be deployed to address environmental health
      issues, especially as they relate to environmental justice concerns.

PMID- 21721501
TI  - A burden of disease approach to prioritizing environmental policy initiatives: a
      case study in the Middle East.
AB  - The UNC-Chapel Hill Gillings School of Global Public Health completed a 2.5-year
      project to advise a rapidly developing Middle Eastern nation on strategies for
      reducing environmental risks to public health. The project design, which combined
      quantitative risk assessment with structured stakeholder engagement, provides a
      possible template for a strategic assessment of environmental effects on North
      Carolina medical care costs.

PMID- 21721502
TI  - Integration of environmental stewardship and local economic development to
      enhance community health.
AB  - Environmental groups working to preserve natural ecosystems and groups working to
      enhance local economic development often find themselves on philosophically
      opposite sides of the negotiation table. Case histories of cooperative engagement
      are provided that serve as examples of how environmental stewardship is
      compatible with local economic development and community health.

PMID- 21721503
TI  - Lack of basic amenities: indicators of health disparities in low-income minority
      communities and tribal areas.
AB  - North Carolina has numerous low-income minority communities and tribal areas
      where basic public health amenities are lacking. Disparities in clean air, safe
      drinking water, and toxin-free soil create human exposures that result in poor
      health, depressed property value, and more contaminated environments than are
      present in higher income communities.

PMID- 21721504
TI  - Demographic characteristics of individuals residing near hazardous waste sites in
      North Carolina.

PMID- 21721505
TI  - North Carolina's preparation for gaining the benefits and meeting the
      requirements of national health care reform.
AB  - Passage and signing of the Affordable Care Act (ACA) have not ended the debate
      about the best way to guarantee access to affordable health care. While the
      debate continues, the responsibilities of US states to implement the provisions
      of the ACA remain a reality, pending congressional action or court decisions to
      the contrary.

PMID- 21721506
TI  - Implementation of the Affordable Care Act in North Carolina.

PMID- 21721507
TI  - The National Children's Study in North Carolina: a study of the effect of the
      environment on children's health, growth, and development.
AB  - The National Children's Study, a longitudinal cohort study exploring
      relationships among broadly defined environmental exposures and children's
      health, is assessing whether these exposures are harmful, harmless, or helpful.
      The study is presently underway in 37 locations (2 of which are in North
      Carolina) and will expand to enroll 100,000 children across the United States.

PMID- 21721508
TI  - En route to a molecular sheaf: active metal template synthesis of a [3]rotaxane
      with two axles threaded through one ring.
AB  - We report that a 2,2':6',2"-terpyridylmacrocycle-Ni complex can efficiently
      mediate the threading of two alkyl chains with bulky end groups in an active
      metal template sp(3)-carbon-to-sp(3)-carbon homocoupling reaction, resulting in a
      rare example of a doubly threaded [3]rotaxane in up to 51% yield. The unusual
      architecture is confirmed by X-ray crystallography (the first time that a one
      ring-two-thread [3]rotaxane has been characterized in the solid state) and is
      found to be stable with respect to dethreading despite the large ring size of the
      macrocycle. Through such active template reactions, in principle, a macrocycle
      should be able to assemble as many axles in its cavity as the size of the ring
      and the stoppers will allow. A general method for threading multiple axles
      through a macrocycle adds significantly to the tools available for the synthesis
      of different types of rotaxane architectures.

PMID- 21721509
TI  - A dually effective inorganic salt at inducing obvious viscoelastic behavior of
      both cationic and anionic surfactant solutions.
AB  - Hydrazine nitrate (HN), an inorganic salt, was first found to have dual effects
      on inducing obvious viscoelasticity of both cationic and anionic surfactant
      solutions. It was interesting that the surfactant solutions exhibited
      characteristic wormlike micelle features with strong viscoelastic properties upon
      the addition of this inorganic salt. The rheological properties of the surfactant
      solutions have been measured and discussed. The apparent viscosity of the
      solutions showed a volcano change with an increase of the HN concentration.
      Correspondingly, the microstructures of the micelles in the solutions changed
      with the apparent viscosity. First, wormlike micelles began to form and grew with
      an increase of the HN concentration. Subsequently, the systems exhibited linear
      viscoelasticity with characteristics of a Maxwell fluid in the intermediate mass
      fraction range, which originated from a 3D entangled network of wormlike
      micelles. Finally, a transition from linear micelles to branched ones probably
      took place at higher HN contents. In addition, the origin of the dual effects
      brought by HN addition on inducing viscoelasticity in both cationic and anionic
      surfactant solutions was investigated.

PMID- 21721510
TI  - Surface-confined conformers and coassembly-induced conformer resolution.
AB  - Stereoisomerism is a fundamental chemistry issue and has been intensively
      investigated because of its importance in organic chemistry, biology, and
      pharmacology. Molecules with freely rotatable single bonds have many
      interconvertable conformers. Herein, we report the surface-adsorption-induced
      conformer resolution by employing azobenzene-3,3-dicarboxylic acid (ADA-33) as a
      model compound. Two linear assembly phases composed of trans conformers on a
      highly oriented pyrolytic graphite (HOPG) surface are observed by scanning
      tunneling microscopy. With the codeposition with 1-octanoic acid (OA), only one
      trans conformer of ADA-33 can be recognized by OA to form a two-component
      assembly with alternately arranged ADA-33 and OA stripes, which can be attributed
      to the epitaxial assembly of ADA-33 and OA on the HOPG surface, and weak hydrogen
      bonding exists between conformer I and OA molecules. The results are of
      significance with respect to the discrimination and resolution of conformers on a
      solid surface and provide molecular insights into the coadsorption assembly on
      the surface.

PMID- 21721512
TI  - Resonant photoconductance of molecular junctions formed in gold nanoparticle
      arrays.
AB  - We investigate the photoconductance properties of oligo(phenylene vinylene) (OPV)
      molecules in metal-molecule-metal junctions. The molecules are electrically
      contacted in a two-dimensional array of gold nanoparticles. The nanoparticles in
      such an array are separated by only few nanometers. This allows to bridge the
      distance between the nanoparticles with molecules considered as molecular wires
      such as OPV. We report on the photoconductance of electrically contacted OPV upon
      resonant optical excitation of the molecules. This resonant photoconductance is
      sublinear in laser intensity, which suggests that trap state dynamics of the
      optically excited charge carriers dominate the optoelectronic response.

PMID- 21721511
TI  - Kinase consensus sequences: a breeding ground for crosstalk.
AB  - The best characterized examples of crosstalk between two or more different post
      translational modifications (PTMs) occur with respect to histones. These examples
      demonstrate the critical roles that crosstalk plays in regulating cell signaling
      pathways. Recently, however, non-histone crosstalk has been observed between
      serine/threonine phosphorylation and the modification of arginine and lysine
      residues within kinase consensus sequences. Interestingly, many kinase consensus
      sequences contain critical arginine/lysine residues surrounding the substrate
      serine/threonine residue. Therefore, we hypothesize that non-histone crosstalk
      between serine/threonine phosphorylation and arginine/lysine modifications is a
      global mechanism for the modulation of cellular signaling. In this review, we
      discuss several recent examples of non-histone kinase consensus sequence
      crosstalk, as well as provide the biophysical basis for these observations. In
      addition, we predict likely examples of crosstalk between protein arginine
      methyltransferase 1 (PRMT1) and Akt and discuss the future implications of these
      findings.

PMID- 21721514
TI  - Core-extended perylene tetracarboxdiimides: the homologous series of coronene
      tetracarboxdiimides.
AB  - Two novel coronenediimide (CDI) derivatives, CDI 2 and dinaphtho-CDI 4, were
      synthesized via straightforward synthetic routes completing the homologous series
      of coronene tetracarboxdiimides, which show remarkable optical properties with
      absorption wavelengths ranging from 380 to 600 nm, high absorption coefficients,
      and high fluorescence quantum yields.

PMID- 21721515
TI  - Panchromatic trichromophoric sensitizer for dye-sensitized solar cells using
      antenna effect.
AB  - The first trichromophoric sensitizer, consisting of covalently linked
      boradiazaindacene (BODIPY), zinc porphyrin (ZnP), and squaraine (SQ) units, has
      been synthesized by Heck alkynylation to obtain a panchromatic dye, for dye
      sensitized solar cells (DSSCs). Efficient intramolecular energy transfers (ET)
      were observed between all chromophoric subunits and enhance the overall
      conversion efficiency by 25%. The antenna effect is demonstrated by the
      photoaction spectrum which features all of a chromophore's absorption bands.

PMID- 21721516
TI  - Magnetic circular dichroism and absorption spectra of methylidyne in a krypton
      matrix.
AB  - Electronic absorption and magnetic circular dichroism spectra are reported for
      the A(2)Delta, B(2)Sigma(-), and C(2)Sigma(+) <- X(2)Pi transitions of
      methylidyne radicals isolated in a Kr matrix at cryogenic temperatures. The
      results are interpreted in the framework of a model in which the X(2)Pi term is
      split by combination of spin-orbit and crystal-field interactions with the atoms
      of the host matrix. Analysis of the zeroth moments of the spectra yields an
      empirical spin-orbit coupling constant A(Pi) = 11 +/- 2 cm(-1) and orbital
      reduction factor kappa = 0.26 +/- 0.05, corresponding to a crystal-field
      splitting of V(Pi) = 43 +/- 10 cm(-1) for the X(2)Pi term. For the A(2)Delta
      excited-state term, analysis of the first MCD moments gives a spin-orbit coupling
      constant of A(Delta) = 4.4 +/- 0.9 cm(-1).

PMID- 21721517
TI  - Posttranslational modifications of the photoreceptor-specific ABC transporter
      ABCA4.
AB  - ABCA4 is a photoreceptor-specific ATP-binding cassette transporter implicated in
      the clearance of all-trans-retinal produced in the retina during light
      perception. Multiple mutations in this protein have been linked to Stargardt
      disease and other visual disorders. Here we report the first systematic study of
      posttranslational modifications in native ABCA4 purified from bovine rod outer
      segments. Seven N-glycosylation sites were detected in exocytoplasmic domains 1
      and 2 by mass spectrometry, confirming the topological model of ABCA4 proposed
      previously. The modifying oligosaccharides were relatively short and homogeneous,
      predominantly representing a high-mannose type of N-glycosylation. Five
      phosphorylation sites were detected in cytoplasmic domain 1, with four of them
      located in the linker "regulatory-like" region conserved among ABCA subfamily
      members. Contrary to published results, phosphorylation of ABCA4 was found to be
      independent of light. Using human ABCA4 mutants heterologously expressed in
      mammalian cells, we showed that the Stargardt disease-associated alanine mutation
      in the phosphorylation site at position 901 led to protein misfolding and
      degradation. Furthermore, replacing the S1317 phosphorylation site reduced the
      basal ATPase activity of ABCA4, whereas an alanine mutation in either the S1185
      or T1313 phosphorylation site resulted in a significant decrease in the all-trans
      retinal-stimulated ATPase activity without affecting the basal activity, protein
      expression, or localization. In agreement with this observation, partial
      dephosphorylation of native bovine ABCA4 led to reduction of both basal and
      stimulated ATPase activity. Thus, we present the first evidence that
      phosphorylation of ABCA4 can regulate its function.

PMID- 21721518
TI  - Global aquatic passive sampling: maximizing available resources using a novel
      exposure procedure.

PMID- 21721519
TI  - Bioactive 11,20-epoxy-3,5(16)-diene briarane diterpenoids from the South China
      Sea gorgonian Dichotella gemmacea.
AB  - Seven new briarane diterpenoids, gemmacolides G-M (1-7), were isolated together
      with two known analogues, juncin O and junceellolide C, from the South China Sea
      gorgonian Dichotella gemmacea. The structures of the new compounds were
      elucidated by detailed analysis of spectroscopic data and comparison with
      reported data. In an in vitro bioassay, these compounds exhibited different
      levels of growth inhibition activity against A549 and MG63 cells. In particular,
      compound 4 was more active than the positive control adriamycin against A549
      cells. Compounds 4 and 7 also exhibited weak antimicrobial activity against the
      bacterium Bacillus megaterium and the fungus Septoria tritici, respectively.

PMID- 21721520
TI  - Parallel synthesis of a desketoraloxifene analogue library via
      iodocyclization/palladium-catalyzed coupling.
AB  - For a future structure-activity relationship (SAR) study, a library of
      desketoraloxifene analogues has been prepared by parallel synthesis using
      iodocyclization and subsequent palladium-catalyzed coupling reactions. Points of
      desketoraloxifene diversification involve the two phenolic hydroxyl groups and
      the aliphatic amine side chain. This approach affords oxygen-bearing 3
      iodobenzo[b]thiophenes 4 in excellent yields, which are easily further elaborated
      using a two-step approach involving Suzuki-Miyaura and Mitsunobu coupling
      reactions to give multimethoxy-substituted desketoraloxifene analogues 6. Various
      hydroxyl-substituted desketoraloxifene analogues 7 were subsequently generated by
      demethylation with BBr(3).

PMID- 21721521
TI  - A new ring expansion for a chiral hexahydroazulene skeleton possessing an angular
      methyl group.
AB  - A new synthetic route for a pseudoguaiane ring system is described. The synthesis
      features an Ireland-Claisen rearrangement for constructing the trans-fused ring
      system, followed by a new ring expansion to yield a bicyclo[5.3.0]decane ring
      system possessing an angular methyl group.

PMID- 21721522
TI  - Xylan-rich hemicelluloses-graft-acrylic acid ionic hydrogels with rapid responses
      to pH, salt, and organic solvents.
AB  - Exploitation of biomaterials derived from renewable resources is an important
      approach to address environmental and resource problems in the world today. In
      this paper, novel ionic hydrogels based on xylan-rich hemicelluloses were
      prepared by free radical graft copolymerization of acrylic acid (AA) and xylan
      rich hemicelluloses (XH) by using N,N-methylene-bis(acrylamide) (MBA) as cross
      linker and ammonium persulfate/N,N,N',N'-tetramethylethylenediamine (APS/TMEDA)
      as redox initiator system. The network characteristics of the ionic hydrogels
      were investigated by Fourier transform infrared spectroscopy (FT-IR) and scanning
      electron microscopy (SEM), as well as by determination of mechanical properties,
      swelling, and stimuli responses to pH, salts, and organic solvents. The results
      showed that an increase in the MBA/XH or AA/XH ratio resulted in higher cross
      linking density of the network and thus decreased the swelling ratio. Expansion
      of the network hydrogels took place at high pH, whereas shrinkage occurred at low
      pH or in salt solutions as well as in organic solvents. The ionic hydrogels had
      high water adsorption capacity and showed rapid and multiple responses to pH,
      ions, and organic solvents, which may allow their use in several areas such as
      adsorption, separation, and drug release systems.

PMID- 21721523
TI  - Iron silylamide-grafted periodic mesoporous silica.
AB  - The surface chemistry of a series of well-defined metalorganic ferrous and ferric
      iron complexes on periodic mesoporous silica (PMS) was investigated. In addition
      to literature known Fe(II)[N(SiMe(3))(2)](2)(THF), Fe(II)[N(SiPh(2)Me(2))(2)](2),
      and Fe(III)[N(SiMe(3))(2)](2)Cl(THF), the new complexes
      [Fe(II){N(SiHMe(2))(2)}(2)](2) and Fe(III)[N(SiHMe(2))(2)](3)(MU-Cl)Li(THF)(3)
      were employed as grafting precursors. Selection criteria for the molecular
      precursors were the molecular size (monoiron versus diiron species), the
      oxidation state of the iron center (II versus III), and the functionality of the
      silylamido ligand (e.g., built-in spectroscopic probes). Hexagonal channel-like
      MCM-41 and cubic cage-like SBA-1 were chosen as two distinct PMS materials. The
      highest iron load (12.8 wt %) was obtained for hybrid material
      [Fe(II){N(SiHMe(2))(2)}(2)](2)@MCM-41 upon stirring the reaction mixture iron
      silylamide/PMS/n-hexane for 18 h at ambient temperature. Size-selective grafting
      and concomitantly extensive surface silylation were found to be prominent for
      cage-like SBA-1. Here, the surface metalation is governed by the type of iron
      precursor, the pore size, the reaction time, and the solvent. The formation of
      surface-attached iron-ligand species is discussed on the basis of diffuse
      reflectance infrared Fourier transform (DRIFT) and electron paramagnetic
      resonance (EPR) spectroscopy, nitrogen physisorption, and elemental analysis.

PMID- 21721524
TI  - On the nature of the oxidative heterocoupling of lithium enolates.
AB  - The coupling of enolates through single-electron oxidation is one of the most
      direct routes for generating 1,4-dicarbonyls. Recent work on the intermolecular
      heterocoupling of equimolar amounts of two different enolates through single
      electron oxidation has shown that synthetically useful yields beyond those
      predicted by statistics can be obtained. To determine the underlying basis for
      the selective formation of heterocoupled products, kinetic, (7)Li NMR, and
      synthetic studies were performed. The collection of data obtained from these
      experiments shows that the selective formation of heterocoupled products is a
      consequence of heteroaggregation of lithium enolates.

PMID- 21721525
TI  - In vivo PET imaging of histone deacetylases by 18F-suberoylanilide hydroxamic
      acid (18F-SAHA).
AB  - Histone deacetylases (HDACs) are a group of enzymes that modulate gene expression
      and cell state by deacetylation of both histone and non-histone proteins. A
      variety of HDAC inhibitors (HDACi) have already undergone clinical testing in
      cancer. Real-time in vivo imaging of HDACs and their inhibition would be
      invaluable; however, the development of appropriate imaging agents has remained a
      major challenge. Here, we describe the development and evaluation of (18)F
      suberoylanilide hydroxamic acid ((18)F-SAHA 1a), a close analogue of the most
      clinically relevant HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). We
      demonstrate that 1a has near identical biochemical activity profiles to that of
      SAHA and report findings from pharmacokinetic studies. Using a murine ovarian
      cancer model, we likewise show that HDAC inhibitor target binding efficacy can be
      quantitated within 24 h of administration. 1a thus represents the first (18)F
      positron emission tomography (PET) HDAC imaging agent, which also exhibits low
      nanomolar potency and is pharmacologically analogous to a clinically relevant
      HDAC inhibitor.

PMID- 21721526
TI  - Highly stable chiral (A)6-B supramolecular copolymers: a multivalency-based self
      assembly process.
AB  - A novel type of chiral layered supramolecular copolymer with high molecular
      weight has been assembled from a hydrogen bonded C(6)-symmetric zinc porphyrin
      hexamer and chiral C(3)-symmetric pyridine hexadentate linkers driven by
      multivalent zinc porphyrin-pyridine coordination. UV-vis, circular dichroism, and
      static light scattering experiments revealed that the formation of the layered
      supramolecular copolymers is at first dynamically controlled and then becomes
      thermodynamically controlled.

PMID- 21721527
TI  - Multielement fingerprinting as a tool in origin authentication of PGI food
      products: Tropea red onion.
AB  - Tropea red onion ( Allium cepa L. var. Tropea) is among the most highly
      appreciated Italian products. It is cultivated in specific areas of Calabria and,
      due to its characteristics, was recently awarded with the protected geographical
      indications (PGI) certification from the European Union. A reliable
      classification of onion samples in groups corresponding to "Tropea" and "non
      Tropea" categories is now available to the producers. This important goal has
      been achieved through the evaluation of three supervised chemometric approaches.
      Onion samples with PGI brand (120) and onion samples not cultivated following the
      production regulations (80) were digested by a closed-vessel microwave oven
      system. ICP-MS equipped with a dynamic reaction cell was used to determine the
      concentrations of 25 elements (Al, Ba, Ca, Cd, Ce, Cr, Dy, Eu, Fe, Ga, Gd, Ho,
      La, Mg, Mn, Na, Nd, Ni, Pr, Rb, Sm, Sr, Tl, Y, and Zn). The multielement
      fingerprint was processed using linear discriminant analysis (LDA) (standard and
      stepwise), soft independent modeling of class analogy (SIMCA), and back
      propagation artificial neural network (BP-ANN). The cross-validation procedure
      has shown good results in terms of the prediction ability for all of the
      chemometric models: standard LDA, 94.0%; stepwise LDA, 94.5%; SIMCA, 95.5%; and
      BP-ANN, 91.5%.

PMID- 21721528
TI  - Synthesis and structure-activity evaluation of isatin-beta-thiosemicarbazones
      with improved selective activity toward multidrug-resistant cells expressing P
      glycoprotein.
AB  - Cancer multidrug resistance (MDR) mediated by ATP-binding cassette (ABC)
      transporters presents a significant unresolved clinical challenge. One strategy
      to resolve MDR is to develop compounds that selectively kill cells overexpressing
      the efflux transporter P-glycoprotein (MDR1, P-gp, ABCB1). We have previously
      reported structure-activity studies based around the lead compound NSC73306 (1, 1
      isatin-4-(4'-methoxyphenyl)-3-thiosemicarbazone, 4.3-fold selective). Here we
      sought to extend this work on MDR1-selective analogues by establishing whether 1
      showed "robust" activity against a range of cell lines expressing P-gp. We
      further aimed to synthesize and test analogues with varied substitution at the N4
      position, and substitution around the N4-phenyl ring of isatin-beta
      thiosemicarbazones (IBTs), to identify compounds with increased MDR1-selectivity.
      Compound 1 demonstrated MDR1-selectivity against all P-gp-expressing cell lines
      examined. This selectivity was reversed by inhibitors of P-gp ATPase activity.
      Structural variation at the 4'-phenyl position of 1 yielded compounds of greater
      MDR1-selectivity. Two of these analogues, 1-isatin-4-(4'-nitrophenyl)-3
      thiosemicarbazone (22, 8.3-fold selective) and 1-isatin-4-(4'-tert-butyl phenyl)
      3-thiosemicarbazone (32, 14.8-fold selective), were selected for further testing
      and were found to retain the activity profile of 1. These compounds are the most
      active IBTs identified to date.

PMID- 21721529
TI  - CO2-filling capacity and selectivity of carbon nanopores: synthesis, texture, and
      pore-size distribution from quenched-solid density functional theory (QSDFT).
AB  - Porous carbons synthesized by KOH activation of petroleum coke can have high
      surface areas, over 3000 m(2)/g, and high CO(2) sorption capacity, over 15 wt %
      at 1 bar. This makes them attractive sorbents for carbon capture from combustion
      flue gas. Quenched solid density functional theory (QSDFT) analysis of high
      resolution nitrogen-sorption data for such materials leads to the conclusion that
      it is the pores smaller than 1 nm in diameter that fill with high-density CO(2)
      at atmospheric pressure. Upon increasing pressure, larger and larger pores are
      filled, up to about 4 nm at 10 bar. An ideal CO(2)/N(2) selectivity of such
      carbon materials tends to decrease substantially upon increasing pressure, for
      example, from about 8-10 at 1 bar to about 4-5 at 10 bar. All in all, this work
      confirms the robust CO(2)-filling properties of porous carbon sorbents, their low
      pressure selectivity advantages, and points to the critical role of <1 nm pores
      that can be controlled with activation conditions.

PMID- 21721530
TI  - Universal analytical scattering form factor for shell-, core-shell, or
      homogeneous particles with continuously variable density profile shape.
AB  - A novel analytical and continuous density distribution function with a widely
      variable shape is reported and used to derive an analytical scattering form
      factor that allows us to universally describe the scattering from particles with
      the radial density profile of homogeneous spheres, shells, or core-shell
      particles. Composed by the sum of two Fermi-Dirac distribution functions, the
      shape of the density profile can be altered continuously from step-like via
      Gaussian-like or parabolic to asymptotically hyperbolic by varying a single
      "shape parameter", d. Using this density profile, the scattering form factor can
      be calculated numerically. An analytical form factor can be derived using an
      approximate expression for the original Fermi-Dirac distribution function. This
      approximation is accurate for sufficiently small rescaled shape parameters, d/R
      (R being the particle radius), up to values of d/R ~ 0.1, and thus captures step
      like, Gaussian-like, and parabolic as well as asymptotically hyperbolic profile
      shapes. It is expected that this form factor is particularly useful in a model
      dependent analysis of small-angle scattering data since the applied continuous
      and analytical function for the particle density profile can be compared directly
      with the density profile extracted from the data by model-free approaches like
      the generalized inverse Fourier transform method.

PMID- 21721531
TI  - Microwave-assisted and continuous flow multistep synthesis of 4-(pyrazol-1
      yl)carboxanilides.
AB  - A series of 4-(pyrazol-1-yl)carboxanilides active as inhibitors of canonical
      transient receptor potential channels were synthesized in an efficient three-step
      protocol using controlled microwave heating. The general synthetic strategy
      involves condensation of 4-nitrophenylhydrazine with appropriate 1,3-dicarbonyl
      building blocks, followed by reduction of the nitro group to the amine, which is
      then amidated with carboxylic acids. Compared to the conventional protocol a
      dramatic reduction in overall processing time from ~2 days to a few minutes was
      achieved, accompanied by significantly improved product yields. In addition, the
      first two steps in the synthetic pathway were also performed under continuous
      flow conditions providing similar isolated product yields. As an alternative to
      the three-step protocol, a novel two-step route to the desired 4-(pyrazol-1
      yl)carboxanilides was devised involving condensation of 4-bromophenylhydrazine
      with appropriate 1,3-dicarbonyl building blocks, followed by Pd-catalyzed
      Buchwald-Hartwig amidation with carboxylic acid amides.

PMID- 21721532
TI  - Electrochemical sensing of ethylene employing a thin ionic-liquid layer.
AB  - We introduce an electrochemical ethylene sensor that employs a thin layer of
      ionic liquid as electrolyte. Ethylene is oxidized in a potential window starting
      ~600 mV before the onset of the gold working electrode oxidation, which inhibits
      the ethylene oxidation at high applied potential. The current amplitude and
      sensor response time depend on the ionic-liquid film thickness, relative
      humidity, and applied potential, in agreement with a theoretical model based on
      diffusion. A detection limit of 760 ppb and a linear response up to 10 ppm were
      achieved. As illustrated by the detection of ethylene, ionic liquids could serve
      as an alternative electrolyte for many electrochemical gas sensors that
      heretofore relied on a strongly acidic electrolyte.

PMID- 21721533
TI  - Exploring interactions between the 49 kDa and ND1 subunits in mitochondrial NADH
      ubiquinone oxidoreductase (complex I) by photoaffinity labeling.
AB  - Quinazolines are strong inhibitors of NADH-ubiquinone oxidoreductase (complex I)
      from bovine heart mitochondria. Using a photoreactive quinazoline, [(125)I]AzQ,
      and bovine heart submitochondrial particles (SMPs), we demonstrated previously
      that [(125)I]AzQ binds at the interface of the 49 kDa and ND1 subunits in complex
      I; it labeled a site in the N-terminal (Asp41-Arg63) region of the 49 kDa
      subunit, suggesting that this region contacts the ND1 subunit [Murai, M., et al.
      (2009) Biochemistry 48, 688-698]. The labeled region of ND1 could not be
      identified because it is highly hydrophobic, and the SMPs did not yield
      sufficient amounts of labeled protein. Here, we describe how photoaffinity
      labeling of isolated complex I by [(125)I]AzQ yielded sufficient material for
      identification of the labeled region of the ND1 subunit. The inhibition of the
      isolated enzyme by AzQ is comparable to that of SMPs. Our results reveal that the
      labeled site in ND1 is between Asp199 and Lys262, mostly likely in the third
      matrix loop that connects the fifth and sixth transmembrane helices. Thus, our
      results reveal new information about the interface between the hydrophilic and
      hydrophobic domains of complex I, a region that is thought to be important for
      ubiquinone reduction and energy transduction.

PMID- 21721534
TI  - Rechargeable biofilm-controlling tubing materials for use in dental unit water
      lines.
AB  - A simple and practical surface grafting approach was developed to introduce
      rechargeable N-halamine-based antimicrobial functionality onto the inner surfaces
      of continuous small-bore polyurethane (PU) dental unit waterline (DUWL) tubing.
      In this approach, tetrahydrofuran (THF) solution of a free-radical initiator,
      dicumyl peroxide (DCP), flowed through the PU tubing (inner diameter of 1/16 in.,
      or 1.6 mm) to diffuse DCP into the tubing's inner walls, which was used as
      initiator in the subsequent grafting polymerization of methacrylamide (MAA) onto
      the tubing. Upon chlorine bleach treatment, the amide groups of the grafted MAA
      side chains were transformed into acyclic N-halamines. The reactions were
      confirmed with attenuated total reflectance infrared (ATR) spectra and iodometric
      titration. The mechanical properties of the tubing were not significantly
      affected by the grafting reactions. The biofilm-controlling function of the new N
      halamine-based PU tubing was evaluated with Pseudomonas aeruginosa (P.
      aeruginosa), one of the most isolated water bacteria from DUWLs, in a continuous
      bacterial flow model. Bacteria culturing and SEM studies showed that the inner
      surfaces of the new N-halamine-based PU tubing completely prevented bacterial
      biofilm formation for at least three to four weeks. After that, bacteria began to
      colonize the tubing surface. However, the lost function was fully regenerated by
      exposing the tubing inner surfaces to diluted chlorine bleach. The recharging
      process could be repeated periodically to further extend the biofilm-controlling
      duration for long-term applications.

PMID- 21721536
TI  - Spatial distribution of hexachlorocyclohexanes in agricultural soils in Zhejiang
      province, China, and correlations with elevation and temperature.
AB  - Large quantities of hexachlorocyclohexanes (HCHs) were historically applied to
      soils in Zhejiang, a hilly province of eastern China, yet very limited
      information is publicly available for the present levels and residue
      characteristics of HCHs in the region. In this work, concentrations of HCHs and
      enantiomeric fractions (EFs) of alpha-isomer were analyzed in 58 agricultural
      soil samples (0-20 cm) collected in Zhejiang province. On the basis of the ratio
      of alpha-HCH/beta-HCH and the fact that HCHs were banned in 1983 for agricultural
      use in China, fresh application of technical HCHs in a large quantity was
      unlikely in this province. Significant correlation was found between soil
      concentrations and elevation (R = 0.52, P < 0.001) and temperature (R = -0.55, P
      < 0.0001), but not between soil concentrations and total technical usage (R = 
      0.24, P = 0.1), suggesting a typical secondary distribution pattern. The soil
      residue inventories of HCHs derived from the relationship between concentration
      and elevation indicated 14.2 tons of HCHs left in agricultural soils in plain
      areas with the average elevation less than 100 m, and 61.6 tons of HCHs left in
      mountain soils with the average elevation higher than 100 m. It was also found
      that EFs of alpha-HCH were significantly negatively correlated with carbon
      biomass (C(bio)) in soils. This implies that C(bio) might have important impact
      on orientation and extent of enantioselective degradation of alpha-HCH in the
      region, which is, according to our knowledge, the first report of this kind.

PMID- 21721535
TI  - Two functional S100A4 monomers are necessary for regulating nonmuscle myosin-IIA
      and HCT116 cell invasion.
AB  - S100A4, a member of the Ca(2+)-activated S100 protein family, regulates the
      motility and invasiveness of cancer cells. Moreover, high S100A4 expression
      levels correlate with poor patient survival in several cancers. Although
      biochemical, biophysical, and structural data indicate that S100A4 is a
      noncovalent dimer, it is unknown if two functional S100A4 monomers are required
      for the productive recognition of protein targets and the promotion of cell
      invasion. To address this question, we created covalently linked S100A4 dimers
      using a glycine rich flexible linker. The single-chain S100A4 (sc-S100A4)
      proteins exhibited wild-type affinities for calcium and nonmuscle myosin-IIA,
      retained the ability to regulate nonmuscle myosin-IIA assembly, and promoted
      tumor cell invasion when expressed in S100A4-deficient colon carcinoma cells.
      Mutation of the two calcium-binding EF-hands in one monomer, while leaving the
      other monomer intact, caused a 30-60-fold reduction in binding affinity for
      nonmuscle myosin-IIA concomitant with a weakened ability to regulate the monomer
      polymer equilibrium of nonmuscle myosin-IIA. Moreover, sc-S100A4 proteins with
      one monomer deficient in calcium responsiveness did not support S100A4-mediated
      colon carcinoma cell invasion. Cross-linking and titration data indicate that the
      S100A4 dimer binds a single myosin-IIA target peptide. These data are consistent
      with a model in which a single peptide forms interactions in the vicinity of the
      canonical target binding cleft of each monomer in such a manner that both target
      binding sites are required for the efficient interaction with myosin-IIA.

PMID- 21721537
TI  - Influence of structural variations in cationic and anionic moieties on the
      polarity of ionic liquids.
AB  - The polarity of a series of ionic liquids (ILs) arising from the quaternarization
      of N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, N-methylazepane,
      4-hydroxy-1-methylpiperidine, 1,2-dimethylimidazole, and 1-methylimidazole with
      simple alkyl chains and/or hydroxyl (mono- or dihydroxyl) functionalized alkyl
      chains and having bistriflimide, dicyanamide, or nitrate as counteranions has
      been investigated using solvatochromic dyes and expressed in terms of E(T)(N) and
      Kamlet-Taft parameters (dipolarity/polarizability (pi*), hydrogen bond donor
      acidity (alpha), and hydrogen bond basicity (beta)). Significant variations of
      polarity were observed on changing the anion and cation combination. The
      resulting E(T)(N) and alpha values were strongly anion dependent; on going from
      bistriflimide to dicyanamide, a significant decrease in E(T)(N) and alpha values
      was observed. On the other hand, the alkyl chain length has only a moderate
      effect on these parameters; either an increase or decrease in E(T)(N) and alpha
      values was observed on increasing the alkyl chain length, depending on the cation
      core. In the case of cyclic onium salts, the size of the cation ring affected the
      alpha parameter; the ILs based on the seven-membered ring system N-methyl-N
      butylazepanium (also named N-methyl-N-butylhexamethyleneiminium, [HME(1,4)](+))
      have high polarity values, comparatively to the ILs based on analogous five- and
      six-membered cyclic cations (pyrrolidinium and piperidinium). The introduction of
      the OH groups on the cation alkyl chain increases the polarity; the effect is
      substantial for the first OH group and more moderate for the second. Also, the
      thermosolvatochromism (changes in solvatochromic properties with the change in
      temperature) was studied for four dihydroxyl functionalized ILs. Finally, the
      principal component analysis (PCA) carried out on 67 ILs has shown that there are
      only two statistically relevant parameters: PC1, a weighted sum of E(T)(N) and
      alpha, which is able to discern between the cation core structure,
      functionalization, and cation-anion association, and PC2, very close to beta,
      which is related principally to the anion nature.

PMID- 21721538
TI  - A sulfonium cation intermediate in the mechanism of methionine sulfoxide
      reductase B: a DFT study.
AB  - The hybrid density functional theory method B3LYP in combination with three
      systematically larger active site models has been used to investigate the
      substrate binding and catalytic mechanism by which Neisseria gonorrhoeae
      methionine sulfoxide reductase B (MsrB) reduces methionine-R-sulfoxide (Met-R-SO)
      to methionine. The first step in the overall mechanism is nucleophilic attack of
      an active site thiolate at the sulfur of Met-R-SO to form an enzyme-substrate
      sulfurane. This occurs with concomitant proton transfer from an active site
      histidine (His480) residue to the substrates oxygen center. The barrier for this
      step, calculated using our largest most complete active site model, is 17.2 kJ
      mol(-1). A subsequent conformational rearrangement and intramolecular -OH
      transfer to form an enzyme-derived sulfenic acid ((Cys495)S-OH) is not
      enzymatically feasible. Instead, transfer of a second proton from a second
      histidyl active site residue (His477) to the sulfurane's oxygen center to give
      water and a sulfonium cation intermediate is found to be greatly preferred,
      occurring with a quite low barrier of just 1.2 kJ mol(-1). Formation of the final
      product complex in which an intraprotein disulfide bond is formed with generation
      of methionine preferably occurs in one step via nucleophilic attack of the sulfur
      of a second enzyme thiolate ((Cys440)S(-)) at the S(Cys495) center of the
      sulfonium intermediate with a barrier of 23.8 kJ mol(-1). An alternate pathway
      for formation of the products via a sulfenic acid intermediate involves
      enzymatically feasible, but higher energy barriers. The role and impact of
      hydrogen bonding and active site residues on the properties and stability of
      substrate and mechanism intermediates and the affects of mutating His477 are also
      examined and discussed.

PMID- 21721539
TI  - Benchmarking AMBER force fields for RNA: comparisons to NMR spectra for single
      stranded r(GACC) are improved by revised chi torsions.
AB  - Accurately modeling unpaired regions of RNA is important for predicting
      structure, dynamics, and thermodynamics of folded RNA. Comparisons between NMR
      data and molecular dynamics simulations provide a test of force fields used for
      modeling. Here, NMR spectroscopy, including NOESY, (1)H-(31)P HETCOR, DQF-COSY,
      and TOCSY, was used to determine conformational preferences for single-stranded
      GACC RNA. The spectra are consistent with a conformational ensemble containing
      major and minor A-form-like structures. In a series of 50 ns molecular dynamics
      (MD) simulations with the AMBER99 force field in explicit solvent, initial A-form
      like structures rapidly evolve to disordered conformations. A set of 50 ns
      simulations with revised chi torsions (AMBER99chi force field) gives two primary
      conformations, consistent with the NMR spectra. A single 1.9 MUs MD simulation
      with the AMBER99chi force field showed that the major and minor conformations are
      retained for almost 68% of the time in the first 700 ns, with multiple
      transformations from A-form to non-A-form conformations. For the rest of the
      simulation, random-coil structures and a stable non-A-form conformation
      inconsistent with NMR spectra were seen. Evidently, the AMBER99chi force field
      improves structural predictions for single-stranded GACC RNA compared to the
      AMBER99 force field, but further force field improvements are needed.

PMID- 21721540
TI  - Hydroxyl group recognition by hydrogen-bonding donor and acceptor sites embedded
      in a layered metal-organic framework.
AB  - One of the dominant types of interactions between host and guest molecules is
      hydrogen-bonding, and these interactions can work selectively for a guest
      molecule. Here, we demonstrate a metal-organic framework (MOF) having both
      hydrogen-bonding donor and acceptor sites that are quite effective for selective
      sorption. The MOF selectively interacts with hydroxylic guests in contrast to
      aprotic hydrogen-bonding guests and shows a sorption selectivity for protic
      H(2)O, MeOH, and EtOH guests. Notably, this is the first compound that shows
      complete selectivity in adsorption not for MeCN and MeCHO but for EtOH, which has
      similar fundamental properties except for its proticity.

PMID- 21721541
TI  - Understanding the high solubility of CO2 in an ionic liquid with the
      tetracyanoborate anion.
AB  - The ionic liquid 1-ethyl-3-methylimidazolium tetracyanoborate, [emim][B(CN)(4)],
      shows greater CO(2) solubility than several popular ionic liquids (ILs) of
      different anions including [emim]bis(trifluoromethylsulfonyl)imide
      [emim][Tf(2)N]. Herein, both classical molecular dynamics simulation and quantum
      mechanical calculations were used to understand the high solubility of CO(2) in
      the [emim][B(CN)(4)] IL. We found that the solubility is dictated by the cation
      anion interaction, while the CO(2)-anion interaction plays a secondary role. The
      atom-atom radial distribution functions (RDFs) between cation and anion show
      weaker interaction in [emim][B(CN)(4)] than in [emim][Tf(2)N]. A good correlation
      is observed between gas-phase cation-anion interaction energy with CO(2)
      solubility at 1 bar and 298 K, suggesting that weaker cation-anion interaction
      leads to higher CO(2) solubility. MD simulation of CO(2) in the ILs showed that
      CO(2) is closer to the anion than to the cation and that it interacts more
      strongly with [B(CN)(4)] than with [Tf(2)N]. Moreover, a higher volume expansion
      is observed in [emim][B(CN)(4)] than in [emim][Tf(2)N] at different mole
      fractions of CO(2). These results indicate that [B(CN)(4)] as a small and highly
      symmetric anion is unique in giving a high CO(2) solubility by interacting weakly
      with the cation and thus allowing easy creation of cavity for close contact with
      CO(2).

PMID- 21721542
TI  - Determination of the rotational diffusion tensor of porphycene by 13C and 1H spin
      relaxation methods.
AB  - The longitudinal (13)C and (1)H relaxation rates were determined in porphycene in
      CD(2)Cl(2) solution. These data, augmented by (13)C{(1)H} NOE enhancements were
      numerically analyzed to evaluate the rotational diffusion tensor of the molecule
      and the vibrational correction for the one-bond (13)C-(1)H dipolar couplings. The
      (13)C and (1)H relaxation data seem to be consistent with each other, and the
      emerging picture of the rotational dynamics of porphycene compares well with the
      results that can be found in the literature.

PMID- 21721543
TI  - A Pt-cluster-based heterogeneous catalyst for homogeneous catalytic reactions: X
      ray absorption spectroscopy and reaction kinetic studies of their activity and
      stability against leaching.
AB  - The design and development of metal-cluster-based heterogeneous catalysts with
      high activity, selectivity, and stability under solution-phase reaction
      conditions will enable their applications as recyclable catalysts in large-scale
      fine chemicals production. To achieve these required catalytic properties, a
      heterogeneous catalyst must contain specific catalytically active species in high
      concentration, and the active species must be stabilized on a solid catalyst
      support under solution-phase reaction conditions. These requirements pose a great
      challenge for catalysis research to design metal-cluster-based catalysts for
      solution-phase catalytic processes. Here, we focus on a silica-supported, polymer
      encapsulated Pt catalyst for an electrophilic hydroalkoxylation reaction in
      toluene, which exhibits superior selectivity and stability against leaching under
      mild reaction conditions. We unveil the key factors leading to the observed
      superior catalytic performance by combining X-ray absorption spectroscopy (XAS)
      and reaction kinetic studies. On the basis of the mechanistic understandings
      obtained in this work, we also provide useful guidelines for designing metal
      cluster-based catalyst for a broader range of reactions in the solution phase.

PMID- 21721544
TI  - Large amplitude Fourier transformed AC voltammetric investigation of the active
      state electrochemistry of a copper/aqueous base interface and implications for
      electrocatalysis.
AB  - The higher harmonic components available from large-amplitude Fourier-transformed
      alternating current (FT-ac) voltammetry enable the surface active state of a
      copper electrode in basic media to be probed in much more detail than possible
      with previously used dc methods. In particular, the absence of capacitance
      background current allows low-level Faradaic current contributions of fast
      electron-transfer processes to be detected; these are usually completely
      undetectable under conditions of dc cyclic voltammetry. Under high harmonic FT-ac
      voltammetric conditions, copper electrodes exhibit well-defined and reversible
      premonolayer oxidation responses at potentials within the double layer region in
      basic 1.0 M NaOH media. This process is attributed to oxidation of copper adatoms
      (Cu*) of low bulk metal lattice coordination numbers to surface-bonded, reactive
      hydrated oxide species. Of further interest is the observation that cathodic
      polarization in 1.0 M NaOH significantly enhances the current detected in each of
      the fundamental to sixth FT-ac harmonic components in the Cu*/Cu hydrous oxide
      electron-transfer process which enables the underlying electron transfer
      processes in the higher harmonics to be studied under conditions where the dc
      capacitance response is suppressed; the results support the incipient hydrous
      oxide adatom mediator (IHOAM) model of electrocatalysis. The underlying quasi
      reversible interfacial Cu*/Cu hydrous oxide process present under these
      conditions is shown to mediate the reduction of nitrate at a copper electrode,
      while the mediator for the hydrazine oxidation reaction appears to involve a
      different mediator or active state redox couple. Use of FT-ac voltammetry offers
      prospects for new insights into the nature of active sites and electrocatalysis
      at the electrode/solution interface of Group 11 metals in aqueous media.

PMID- 21721545
TI  - A binary functional substrate for enrichment and ultrasensitive SERS
      spectroscopic detection of folic acid using graphene oxide/Ag nanoparticle
      hybrids.
AB  - Herein graphene oxide/Ag nanoparticle hybrids (GO/PDDA/AgNPs) were fabricated
      according to a self-assembly procedure. Using the obtained GO/PDDA/AgNPs as SERS
      substrates, an ultrasensitive and label-free detection of folic acid in water and
      serum was demonstrated based on the inherent SERS spectra of folic acid. The
      modified graphene oxide exhibited strong enrichment of folic acid due to the
      electrostatic interaction, and the self-assembled Ag nanoparticles greatly
      enhanced the SERS spectra of folic acid, both of which led to an ultrahigh
      sensitivity. Therefore, although the SERS enhancement of p-ATP on GO/PDDA/AgNPs
      was weaker than that on Ag nanoparticles, the SERS signals of folic acid on
      GO/PDDA/AgNPs were much stronger than that on Ag nanoparticles. To improve the
      detection, the concentration of GO/PDDA/AgNPs was optimized to reduce background
      of the graphene oxide. The SERS spectra of the folic acid showed that the minimum
      detected concentration of folic acid in water was as low as 9 nM with a linear
      response range from 9 to 180 nM. To estimate the feasibility of the detection
      method based on GO/PDDA/AgNPs for the practical applications, diluted serum
      containing different concentrations of folic acid was taken as real samples. It
      was established that the sensitivity and the linear range for the folic acid in
      serum were comparable to that in water. This ultrasensitive and label-free SERS
      detection of folic acid based on GO/PDDA/AgNPs offers great potential for
      practical applications of medicine and biotechnology.

PMID- 21721546
TI  - Insulin silences apolipoprotein B mRNA translation by inducing intracellular
      traffic into cytoplasmic RNA granules.
AB  - Insulin is a potent inducer of global mRNA translation and protein synthesis, yet
      it negatively regulates apolipoprotein B (apoB) mRNA translation, via an unknown
      mechanism. ApoB mRNA has a long half-life of 16 h, suggesting intracellular
      storage as mRNPs likely in the form of RNA granules. The availability of apoB
      mRNA for translation may be regulated by the rate of release from translationally
      silenced mRNPs within cytoplasmic foci called processing bodies (P bodies). In
      this report, we directly imaged intracellular apoB mRNA traffic and determined
      whether insulin silences apoB mRNA translation by entering cytoplasmic P bodies.
      We assessed the colocalization of apoB mRNA and beta-globin mRNA (as a control)
      with P body (PB) markers using a strong interaction between the bacteriophage
      capsid protein MS2 and a sequence specific RNA stem-loop structure. We observed
      statistically significant increases in the localization of apoB mRNA into P
      bodies 4-16 h after insulin treatment (by 72-89%). The movement of apoB mRNA into
      cytoplasmic P bodies correlated with reduced translational efficiency as assessed
      by polysomal profiling and measurement of apoB mRNA abundance. PB localization of
      beta-globin mRNA was insensitive to insulin treatment, suggesting selective
      regulation of apoB mRNA by insulin. Overall, our data suggest that insulin may
      specifically silence apoB mRNA translation by reprogramming its mRNA into P
      bodies and reducing the size of translationally competent mRNA pools.
      Translational control via traffic into cytoplasmic RNA granules may be an
      important mechanism for controlling the rate of apoB synthesis and hepatic
      lipoprotein production.

PMID- 21721547
TI  - Glyoxal in aqueous ammonium sulfate solutions: products, kinetics and hydration
      effects.
AB  - Reactions and interactions between glyoxal and salts in aqueous solution were
      studied. Glyoxal was found to react with ammonium to form imidazole, imidazole-2
      carboxaldehyde, formic acid, N-glyoxal substituted imidazole, and minor products
      at very low concentrations. Overall reaction orders and rates for each major
      product were measured. Sulfate ions have a strong and specific interaction with
      glyoxal in aqueous solution, which shifts the hydration equilibria of glyoxal
      from the unhydrated carbonyl form to the hydrated form. This ion-specific effect
      contributes to the observed enhancement of the effective Henry's law coefficient
      for glyoxal in sulfate-containing solutions. The results of UV-vis absorption and
      NMR spectroscopy studies of solutions of glyoxal with ammonium, methylamine, and
      dimethylamine salts reveal that light absorbing compounds require the formation
      of nitrogen containing molecules. These findings have implications on the role of
      glyoxal in the atmosphere, both in models of the contribution of glyoxal to form
      secondary organic aerosol (SOA), the role of nitrogen containing species for
      aerosol optical properties and in predictions of the behavior of other carbonyls
      or dicarbonyls in the atmosphere.

PMID- 21721548
TI  - Calix[4]arene-based 1,3-diconjugate of salicylyl imine having dibenzyl amine
      moiety (L): synthesis, characterization, receptor properties toward Fe2+, Cu2+,
      and Zn2+, crystal structures of its Zn2+ and Cu2+ complexes, and selective
      phosphate sensing by the [ZnL].
AB  - A calix[4]arene conjugate bearing salicylyl imine having dibenzyl moiety (L) has
      been synthesized and characterized, and its ability to recognize three most
      important essential elements of human system, viz., iron, copper, and zinc, has
      been addressed by colorimetry and fluorescence techniques. L acts as a sensor for
      Cu(2+) and Fe(2+) by exhibiting visual color change and for Zn(2+) based on
      fluorescence spectroscopy. L shows a minimum detection limit of 3.96 +/- 0.42 and
      4.51 +/- 0.53 ppm and 45 +/- 4 ppb, respectively, toward Fe(2+), Cu(2+), and
      Zn(2+). The in situ prepared [ZnL] exhibits phosphate sensing among 14 anions
      studied with a detection limit of 247 +/- 25 ppb. The complexes of Zn(2+),
      Cu(2+), and Fe(2+) of L have been synthesized and characterized by different
      techniques. The crystalline nature of the zinc and copper complexes and the
      noncrystalline nature of simple L and its iron complex have been demonstrated by
      powder XRD. The structures of Cu(2+) and Zn(2+) complexes have been established
      by single crystal XRD wherein these were found to be 1:1 monomeric and 2:2
      dimeric, respectively, using N(2)O(2) as binding core. The geometries exhibited
      by the Zn(2+) and the Cu(2+) complexes were found to be distorted tetrahedral and
      distorted square planar, respectively. The iron complex of L exists in 1:1
      stoichiometry as evident from the mass spectrometry and elemental analysis.

PMID- 21721549
TI  - Vibrational spectrum and structure of CoO6: a model compound for molecular oxygen
      reversible binding on cobalt oxides and salts; a combined IR matrix isolation and
      theoretical study.
AB  - The formation and structure of a novel species, a disuperoxo-cobalt dioxide
      complex (CoO(6)), has been investigated using matrix isolation in solid neon and
      argon, coupled to infrared spectroscopy and by quantum chemical methods. It is
      found that CoO(6) can be formed by successive complexation of cobalt dioxide by
      molecular oxygen without activation energy by diffusion of ground state O(2)
      molecules at 9K in the dark. The IR data on one combination and seven
      fundamentals, isotopic effects, and quantum chemical calculations are both
      consistent with an asymmetrical structure with two slightly nonequivalent oxygen
      ligands complexing a cobalt dioxide subunit. Evidence for other, metastable
      states is also presented, but the data are not complete. The electronic structure
      and formation pathway of this unique, formally +VI oxidation state, complex has
      been investigated using several functionals of current DFT within the broken
      symmetry unrestricted formalism. It has been shown that the M06L pure local
      functional well reproduce the experimental observations. The ground electronic
      state is predicted to be an open shell (2)A'' doublet with the quartet states
      above by more than 9 kcal/mol and the sextet lying even higher in energy. The
      ground state has a strong and complex multireference character that hinders the
      use of more precise multireference approaches and requires caution in the
      methodology to be used. The geometrical, energetic, and vibrational properties
      have been computed.

PMID- 21721550
TI  - Shape control of gold nanoparticles by silver underpotential deposition.
AB  - Four different gold nanostructures: octahedra, rhombic dodecahedra, truncated
      ditetragonal prisms, and concave cubes, have been synthesized using a seed
      mediated growth method by strategically varying the Ag(+) concentration in the
      reaction solution. Using X-ray photoelectron spectroscopy and inductively coupled
      plasma atomic emission spectroscopy, we provide quantitative evidence that Ag
      underpotential deposition is responsible for stabilizing the various surface
      facets that enclose the above nanoparticles. Increasing concentrations of Ag(+)
      in the growth solution stabilize more open surface facets, and experimental
      values for Ag coverage on the surface of the particles fit well with a calculated
      monolayer coverage of Ag, as expected via underpotential deposition.

PMID- 21721551
TI  - Probing the thermodynamics of competitive ion binding using minimum energy
      structures.
AB  - Ion binding is known to affect the properties of biomolecules and is directly
      involved in many biochemical pathways. Because of the highly polar environments
      where ions are found, a quantum-mechanical treatment is preferable for
      understanding the energetics of competitive ion binding. Due to computational
      cost, a quantum mechanical treatment may involve several approximations, however,
      whose validity can be difficult to determine. Using thermodynamic cycles, we show
      how intuitive models for complicated ion binding reactions can be built up from
      simplified, isolated ion-ligand binding site geometries suitable for quantum
      mechanical treatment. First, the ion binding free energies of individual, minimum
      energy structures determine their intrinsic ion selectivities. Next, the relative
      propensity for each minimum energy structure is determined locally from the
      balance of ion-ligand and ligand-ligand interaction energies. Finally, the
      environment external to the binding site exerts its influence both through long
      ranged dispersive and electrostatic interactions with the binding site as well as
      indirectly through shifting the binding site compositional and structural
      preferences. The resulting picture unifies field-strength, topological control,
      and phase activation viewpoints into a single theory that explicitly indicates
      the important role of solute coordination state on overall reaction energetics.
      As an example, we show that the Na(+) -> K(+) selectivities can be recovered by
      correctly considering the conformational contribution to the selectivity. This
      can be done even when constraining configuration space to the neighborhood around
      a single, arbitrarily chosen, minimum energy structure. Structural regions around
      minima for K(+)- and Na(+)-water clusters are exhibited that display both
      rigid/mechanical and disordered/entropic selectivity mechanisms for both Na(+)
      and K(+). Thermodynamic consequences of the theory are discussed with an emphasis
      on the role of coordination structure in determining experimental properties of
      ions in complex biological environments.

PMID- 21721552
TI  - Following charge separation on the nanoscale in Cu2O-Au nanoframe hollow
      nanoparticles.
AB  - Cu(2)O-Au nanoframes with different nanolayer thicknesses of Cu(2)O were
      prepared, and their photocatalytic properties in aqueous solutions were studied.
      Cu(2)O semiconductor excitation leads to electron-hole separation. In aqueous
      solution, the hole is known to oxidize water to produce hydroxyl radicals whose
      concentration (and that of the holes) can be monitored by the rate of the
      degradation of dissolved methylene blue dye. The exciton lifetime is determined
      by femtosecond techniques and is determined by electron-hole recombination which
      depends on the rates of a number of competing processes such as, electron or hole
      transfer to an acceptor such as a gold nanoframe and/or the electron or hole
      trapping processes at the Cu(2)O-Au nanoframe interface. We measured the exciton
      lifetime as a function of the average Cu(2)O-Au layer separation. A good
      correlation was found between the rate of the photocatalytic degradation of
      methylene blue and the exciton lifetime. The exciton lifetime is found to
      increase as the Cu(2)O thickness is increased. This leads to an increase in the
      electron-hole separation time and thus an increase in the hole (and so the
      hydroxyl radical) concentration leading to an observed enhanced rate of the dye
      degradation.

PMID- 21721553
TI  - Qualitative and quantitative analysis of steroidal saponins in crude extract and
      bark powder of Yucca schidigera Roezl.
AB  - Steroidal saponins in commercial stem syrup and in extract of a bark of Yucca
      schidigera were identified with high-performance liquid chromatography ion trap
      mass spectrometry and quantitated using ultraperformance liquid chromatography
      with quadrupole mass spectrometric detection. Fragmentation patterns of yucca
      saponins were generated using collision-induced dissociation and compared with
      fragmentation of authentic standards as well as with published spectrometric
      information. In addition to detection of twelve saponins known to occur in Y.
      schidigera, collected fragmentation data led to tentative identifications of
      seven new saponins. A quantitation method for all 19 detected compounds was
      developed and validated. Samples derived from the syrup and the bark of yucca
      were quantitatively measured and compared. Obtained results indicate that yucca
      bark accumulates polar, bidesmosidic saponins, while in the stem steroidal
      glycosides with middle- and short-length saccharide chains are predominant. The
      newly developed method provides an opportunity to evaluate the composition of
      yucca products available on the market.

PMID- 21721554
TI  - Fluorescence probe for lysophospholipase C/NPP6 activity and a potent NPP6
      inhibitor.
AB  - Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane
      associated or secreted ectoenzymes that have a role in regulating extracellular
      nucleotide and phospholipid metabolism. Among the members of the NPP family, NPP1
      and -3 act on nucleotides such as ATP, while NPP2, -6, and -7 act on
      phospholipids such as lysophosphatidylcholine and sphingomyelin. NPP6, a recently
      characterized NPP family member, is a choline-specific glycerophosphodiester
      phosphodiesterase, but its functions remain to be analyzed, partly due to the
      lack of highly sensitive activity assay systems and practical inhibitors. Here we
      report synthesis of novel NPP6 fluorescence probes, TG-mPC and its analogues TG
      mPC(3)C, TG-mPC(5)C, TG-mPENE, TG-mPEA, TG-mPhos, TG-mPA, TG-mPMe, and TG-mPPr.
      Among the seven NPPs, only NPP6 hydrolyzed TG-mPC, TG-mPC(3)C, and TG-mPENE. TG
      mPC was hydrolyzed in the cell lysate from NPP6-transfected cells, but not
      control cells, showing that it is suitable for use in cell-based NPP6 assays. We
      also examined the usefulness of TG-mPC as a fluorescence imaging probe. We
      further applied TG-mPC to carry out high-throughput NPP6 inhibitor screening and
      found several NPP6-selective inhibitors in a library of about 80,000 compounds.
      Through structure-activity relationship (SAR) analysis, we identified a potent
      and selective NPP6 inhibitor with an IC(50) value of 0.21 MUM. Our NPP6-selective
      fluorescence probe, TG-mPC, and the inhibitor are expected to be useful to
      elucidate the biological function of NPP6.

PMID- 21721556
TI  - Prolines in betaA-sheet of neural cadherin act as a switch to control the
      dynamics of the equilibrium between monomer and dimer.
AB  - Neural cadherins dimerize through the formation of calcium-dependent strand
      crossover structures. Dimerization of cadherins leads to cell-cell adhesion in
      multicellular organisms. Strand-crossover dimer forms exclusively between the
      first N-terminal extracellular modules (EC1) of the adhesive partners via
      swapping of their betaA-sheets and docking of tryptophan-2 in the hydrophobic
      pocket. In the apo-state wild-type cadherin is predominantly monomer, which
      indicates that the dimerization is energetically unfavorable in the absence of
      calcium. Addition of calcium favors dimer formation by creating strain in the
      monomer and lowering the energetic barrier between monomer and dimer. Dynamics of
      the monomer-dimer equilibrium is vital for plasticity of synapses. Prolines
      recurrently occur in proteins that form strand-crossover dimer and are believed
      to be the source of the strain in the monomer. N-cadherins have two proline
      residues in the betaA-sheet. We focused our studies on the role of these two
      prolines in calcium-dependent dimerization. Spectroscopic, electrophoretic, and
      chromatopgraphic studies showed that mutations of both prolines to alanines
      increased the dimerization affinity by ~20-fold and relieved the requirement of
      calcium in dimerization. The P5A and P6A mutant formed very stable dimers that
      required denaturation of protein to disassemble in the apo conditions. In
      summary, the proline residues act as a switch to control the dynamics of the
      equilibrium between monomer and dimer which is crucial for the plasticity of
      synapses.

PMID- 21721555
TI  - The A53T mutation is key in defining the differences in the aggregation kinetics
      of human and mouse alpha-synuclein.
AB  - Despite a 95% sequence similarity, the aggregation of human and mouse alpha
      synuclein is remarkably different, as the human form is slower than the mouse
      form in forming fibrils but is associated with Parkinson's disease in both humans
      and transgenic mice. Here, the amino acid code underlying these differences is
      investigated by comparing the lag times, growth rates, and secondary structure
      propensities of a systematic series of eight human-mouse chimeras. Fluorescence
      analysis of these variants shows that the A53T substitution dominates the growth
      kinetics, while the lag phase is affected by a combination of the A53T and S87N
      substitutions. The secondary structure propensities derived from an NMR chemical
      shift analysis of the monomeric forms of the human-mouse variants enable us to
      establish a link between the changes in the conformational properties in the
      region of position 53 upon mutation and the corresponding changes in growth
      rates. These results suggest that the presence of an alanine residue at position
      53 may be an evolutionary adaptation to minimize Parkinson's disease in humans
      and indicates that effective drug development efforts may be directed to target
      this N-terminal region of the sequence.

PMID- 21721557
TI  - Single molecule tracking analysis reveals that the surface mobility of amyloid
      oligomers is driven by their conformational structure.
AB  - Several models have been proposed to explain the cytotoxicity of Abeta oligomers.
      The structural polymorphism of the oligomers can account for the various toxic
      effects observed. By combining the use of conformation-specific antibodies and
      single particle tracking techniques, we have investigated the mobility of
      individual Abeta1-42 oligomers on the plasma membrane of living cells. Distinct
      structural types of Abeta1-42 oligomers were labeled with two different
      conformation-specific antibodies. While both types of oligomers showed a
      heterogeneous dynamic behavior, their overall mobility was found to be
      significantly different. Conversely, we discovered that other amyloid oligomers
      sharing a similar conformation but composed of different peptides (amylin and
      prion Sup35NM) display dynamic behaviors comparable to those found for Abeta1-42
      oligomers. This study provides evidence for a link between the quaternary
      structure and the membrane mobility of proteins, revealing that structurally
      analogous supramolecular assemblies diffuse similarly in cells.

PMID- 21721558
TI  - Crystalline covalent organic frameworks with hydrazone linkages.
AB  - Condensation of 2,5-diethoxyterephthalohydrazide with 1,3,5-triformylbenzene or
      1,3,5-tris(4-formylphenyl)benzene yields two new covalent organic frameworks, COF
      42 and COF-43, in which the organic building units are linked through hydrazone
      bonds to form extended two-dimensional porous frameworks. Both materials are
      highly crystalline, display excellent chemical and thermal stability, and are
      permanently porous. These new COFs expand the scope of possibilities for this
      emerging class of porous materials.

PMID- 21721559
TI  - The Laplacian of electron density versus NICSzz scan: measuring magnetic
      aromaticity among molecules with different atom types.
AB  - The electron density versus NICS(zz) (the out-of-plane component of nucleus
      independent chemical shifts (NICS)) scan for assessing magnetic aromaticity among
      similar molecules with different ring sizes is improved by scanning the Laplacian
      of electron density versus NICS(zz) to include molecules containing different
      types of atoms. It is demonstrated that the new approach not only reproduces the
      results of the previous method but also surpasses that in the case of species
      with different atom types. The relative positions of curves in the plots of the
      Laplacian of electron density versus NICS(zz) correlate well with the ring
      current intensities of these molecules both near and far from the ring planes of
      the considered molecules. Accordingly, relative magnetic aromaticity of a number
      of planar hydrocarbons and a group of double aromatic metallic/semimetallic
      species are studied and discussed.

PMID- 21721560
TI  - Revisiting the effects of sequence and structure on the hydrogen bonding and pi
      stacking interactions in nucleic acids.
AB  - Calculated electron densities from PBE0/6-31+G(d,p) were analyzed with respect to
      the hydrogen bonding within a nucleic acid base pair and the pi-stacking between
      sets of base pairs. From published X-ray crystallographic data, base pairs were
      isolated from a total of 11 DNA and RNA duplexes, and their experimental geometry
      was maintained throughout the analyses. Focusing solely on Watson-Crick base
      pairs, from the values of the electron density between interacting nuclei (at the
      bond critical points), we provide quantitative data on individual weak
      interactions. For hydrogen bonding, in addition to quantifying the scissoring
      effect in GC base pairs, the origin of the controversy around the relative
      stability of AT and AU base pairs is identified and resolved. Thus, it is
      illustrated how the conclusion as to their relative stability rests on the
      specific choice of oligonucleotides compared. For pi-stacking, sequence effects
      for tandem AT base pairs are captured, quantified, and explained, and the greater
      sensitivity of GC, over AT, sequences to the rise parameter is established. The
      results presented here show that, from experimental geometries and their electron
      densities, previously determined effects of the sequence and structure of a
      duplex on the stabilizing interactions can be captured, quantified, and traced
      back to the geometry of the base pairs.

PMID- 21721561
TI  - Like-charge guanidinium pairing from molecular dynamics and ab initio
      calculations.
AB  - Pairing of guanidinium moieties in water is explored by molecular dynamics
      simulations of short arginine-rich peptides and ab initio calculations of a pair
      of guanidinium ions in water clusters of increasing size. Molecular dynamics
      simulations show that, in an aqueous environment, the diarginine guanidinium like
      charged ion pairing is sterically hindered, whereas in the Arg-Ala-Arg
      tripeptide, this pairing is significant. This result is supported by the survey
      of protein structure databases, where it is found that stacked arginine pairs in
      dipeptide fragments exist solely as being imposed by the protein structure. In
      contrast, when two arginines are separated by a single amino acid, their
      guanidinium groups can freely approach each other and they frequently form
      stacked pairs. Molecular dynamics simulations results are also supported by ab
      initio calculations, which show stabilization of stacked guanidinium pairs in
      sufficiently large water clusters.

PMID- 21721562
TI  - Full assessment of fate and physiological behavior of quantum dots utilizing
      Caenorhabditis elegans as a model organism.
AB  - We evaluated the in vivo fate and physiological behavior of quantum dots (QDs) in
      Caenorhabditis elegans by GFP transfection, fluorescent imaging, synchrotron
      radiation based elemental imaging, and speciation techniques. The in situ
      metabolism and degradation of QDs in the alimentary system and long-term toxicity
      on reproduction are fully assessed. This work highlights the utility of the C.
      elegans model as a multiflexible platform to allow noninvasively imaging and
      monitoring in vivo consequences of engineered nanomaterials.

PMID- 21721563
TI  - Sorptive characteristics of organomontmorillonite toward organic compounds: a
      combined LFERs and molecular dynamics simulation study.
AB  - Linear free energy relationships (LFER) combined with molecular dynamics (MD)
      simulations were used to investigate the sorptive characteristics of organic
      compounds (OCs) on cetyltrimethylammonium (CTMA) intercalated montmorillonite
      (CTMA-Mont). The LFER for OCs sorption on CTMA-Mont, log K(oc) = (1.45 +/- 0.20)E
      - (0.37 +/- 0.15)S + (0.56 +/- 0.15)A - (1.75 +/- 0.25)B + (2.50 +/- 0.45)V +
      (0.19 +/- 0.35), was obtained by a multiple linear regression of the sorption
      coefficients of the OCs against their solvation descriptors. In comparison to
      water, CTMA-Mont is more polarizable, less polar and cohesive, and has stronger H
      bond acceptor and weaker H-bond donor capacities. Using the above equation we
      calculated that vV and eE were the dominant solvation terms contributing to the
      sorption for all the OCs. MD simulations provided atomic-level insight into the
      interlayer structure of CTMA-Mont. Phenol molecules were shown to be sorbed into
      the nanosized aggregates formed by CTMA alkyl chains. The hydrophobic environment
      within the aggregates is responsible for the sorbent's more polarizable, less
      polar and cohesive characteristics. CTMA-Mont has strong H-bond acceptor and weak
      H-bond donor capacities as oxygen atoms on the siloxane surface act as H-bond
      acceptors for both water and OC molecules. With the combination of the results of
      the two methods, we can provide new insights for understanding the sorptive
      characteristics of organomontmorillonite.

PMID- 21721564
TI  - alpha-Na3M2(PO4)3 (M = Ti, Fe): absolute cationic ordering in NASICON-type
      phases.
AB  - The structure of the fully ordered alpha-Na(3)Ti(2)(PO(4))(3) NASICON compound
      was elucidated using high-quality single-crystal data. The cation/vacancy
      distribution forms a homogeneous 3D arrangement and could represent the absolute
      cationic ordering available in the full Na(3)M(2)(PO(4))(3) series, as verified
      for M = Fe. For M = Ti, the reversible alpha -> gamma transition was observed at
      85  degrees C, leading to the standard disordered R 3c gamma model. Through JPDF
      analysis, the most probable Na(+) zigzag M(2)-M(1) diffusion scheme was directly
      deduced using our accurate crystallographic data.

PMID- 21721565
TI  - Investigation of polypyrrole degradation using electrochemical impedance
      spectroscopy.
AB  - In this paper, the electrochemical degradation of polypyrrole film was studied by
      means of overpotential application. The overpotential was 0.58 V versus SCE, and
      after every 5 min of application of 0.58 V, a cyclic voltammogram was recorded in
      the range of -0.7 to 0.5 V as well as an electrochemical impedance spectroscopy
      and electrochemical quartz crystal microbalance (EIS and EQCM). The main
      characteristic is the huge increase in the charge transfer resistance (r(ct)),
      which indicates that the insertion process of ions in the polymer matrix is
      hindered by the electrochemical degradation. Once the process of insertion is
      damaged, the number of intercalated ions in the matrix should decrease, which is
      expressed by the low-frequency capacitance, which is proportional to the number
      of intercalated ions in the polymeric matrix. The decrease of intercalated ions
      has an influence in the mass variation of the polymer film, which is confirmed by
      EQCM measurements.

PMID- 21721566
TI  - Accurate rates of the complex mechanisms for growth and dissolution of minerals
      using a combination of rare-event theories.
AB  - Mineral growth and dissolution are often treated as occurring via a single
      reversible process that governs the rate of reaction. We show that multiple
      distinct intermediate states can occur during both growth and dissolution.
      Specifically, we used metadynamics, a method for efficiently exploring the free
      energy landscape of a system, coupled to umbrella sampling and reactive flux
      calculations to examine the mechanism and rates of attachment and detachment of a
      barium ion onto a stepped barite (BaSO(4)) surface. The activation energies
      calculated for the rate-limiting reactions, which are different for attachment
      and detachment, precisely match those measured experimentally during both growth
      and dissolution. These results can potentially explain anomalous non-steady-state
      mineral reaction rates observed experimentally and will enable the design of more
      efficient growth inhibitors and facilitate an understanding of the effect of
      impurities.

PMID- 21721567
TI  - Deposition of dense siloxane monolayers from water and trimethoxyorganosilane
      vapor.
AB  - A convenient, laboratory-scale method for the vapor deposition of dense siloxane
      monolayers onto oxide substrates was demonstrated. This method was studied and
      optimized at 110  degrees C under reduced pressure with the vapor of
      tetradecyltris(deuteromethoxy)silane, (CD(3)O)(3)Si(CH(2))(13)CH(3), and water
      from the dehydration of MgSO(4).7H(2)O. Ellipsometric thicknesses, water contact
      angles, Fourier transform infrared (FTIR) spectroscopy, and electrochemical
      capacitance measurements were used to probe monolayer densification. The CD(3)
      stretching mode in the FTIR spectrum was monitored as a function of the
      deposition time and amounts of silane and water reactants. This method probed the
      unhydrolyzed methoxy groups on adsorbed silanes. Excess silane and water were
      necessary to achieve dense, completely hydrolyzed monolayers. In the presence of
      sufficient silane, an excess of water above the calculated stoichiometric amount
      was necessary to hydrolyze all methoxy groups and achieve dense monolayers. The
      excess water was partially attributed to the reversibility of the hydrolysis of
      the methoxy groups.

PMID- 21721568
TI  - Magnetic nanoparticle-mediated gene transfer to oligodendrocyte precursor cell
      transplant populations is enhanced by magnetofection strategies.
AB  - This study has tested the feasibility of using physical delivery methods,
      employing static and oscillating field "magnetofection" techniques, to enhance
      magnetic nanoparticle-mediated gene transfer to rat oligodendrocyte precursor
      cells derived for transplantation therapies. These cells are a major transplant
      population to mediate repair of damage as occurs in spinal cord injury and
      neurological diseases such as multiple sclerosis. We show for the first time that
      magnetic nanoparticles mediate effective transfer of reporter and therapeutic
      genes to oligodendrocyte precursors; transfection efficacy was significantly
      enhanced by applied static or oscillating magnetic fields, the latter using an
      oscillating array employing high-gradient NdFeB magnets. The effects of
      oscillating fields were frequency-dependent, with 4 Hz yielding optimal results.
      Transfection efficacies obtained using magnetofection methods were highly
      competitive with or better than current widely used nonviral transfection methods
      (e.g., electroporation and lipofection) with the additional critical advantage of
      high cell viability. No adverse effects were found on the cells' ability to
      divide or give rise to their daughter cells, the oligodendrocytes-key properties
      that underpin their regeneration-promoting effects. The transplantation potential
      of transfected cells was tested in three-dimensional tissue engineering models
      utilizing brain slices as the host tissue; modified transplanted cells were found
      to migrate, divide, give rise to daughter cells, and integrate within host
      tissue, further evidencing the safety of the protocols used. Our findings
      strongly support the concept that magnetic nanoparticle vectors in conjunction
      with state-of-the-art magnetofection strategies provide a technically simple and
      effective alternative to current methods for gene transfer to oligodendrocyte
      precursor cells.

PMID- 21721569
TI  - Use of real-time, label-free analysis in revealing low-affinity binding to blood
      group antigens by Helicobacter pylori.
AB  - Infectious diseases are often initiated by microbial adherence that is mediated
      by the binding of attachment molecules, termed adhesins, to cell surface
      receptors on host cells. We present an experimental system, oblique-incidence
      reflectivity difference (OI-RD) microscopy, which allows the detection of novel,
      low-affinity microbial attachment mechanisms that may be essential for infectious
      processes. OI-RD microscopy was used to analyze direct binding of the
      oncopathogen, Helicobacter pylori ( H. pylori ) to immobilized glycoconjugates in
      real time with no need for labeling tags. The results suggest the presence of
      additional Lewis b blood group antigen (Le(b)) binding adhesins that have not
      been detected previously. OI-RD microscopy also confirmed the high-affinity
      binding of H. pylori outer-membrane protein BabA to Le(b). The OI-RD microscopy
      method is broadly applicable to real-time characterization of intact microbial
      binding to host receptors and offers new strategies to elucidate the molecular
      interactions of infectious agents with human host cells.

PMID- 21721570
TI  - Structural determinant of chemical reactivity and potential health effects of
      quinones from natural products.
AB  - Although many phenols and catechols found as polyphenol natural products are
      antioxidants and have putative disease-preventive properties, others have
      deleterious health effects. One possible route to toxicity is the bioactivation
      of the phenolic function to quinones that are electrophilic, redox-agents capable
      of modifying DNA and proteins. The structure-property relationships of
      biologically important quinones and their precursors may help understand the
      balance between their health benefits and risks. We describe a mass-spectrometry
      based study of four quinones produced by oxidizing flavanones and flavones. Those
      with a C2-C3 double bond on ring C of the flavonoid stabilize by delocalization
      of an incipient positive charge from protonation and render the protonated
      quinone particularly susceptible to nucleophilic attack. We hypothesize that the
      absence of this double bond is one specific structural determinant that is
      responsible for the ability of quinones to modify biological macromolecules.
      Those quinones containing a C2-C3 single bond have relatively higher aqueous
      stability and longer half-lives than those with a double bond at the same
      position; the latter have short half-lives at or below ~1 s. Quinones with a C2
      C3 double bond show little ability to depurinate DNA because they are rapidly
      hydrated to unreactive species. Molecular-orbital calculations support that
      quinone hydration by a highly structure-dependent mechanism accounts for their
      chemical properties. The evidence taken together support a hypothesis that those
      flavonoids and related natural products that undergo oxidation to quinones and
      are then rapidly hydrated are unlikely to damage important biological
      macromolecules.

PMID- 21721571
TI  - Platinum interference with siRNA non-seed regions fine-tunes silencing capacity.
AB  - Knowledge concerning the molecular mechanisms governing the influence of non
      coding RNAs on protein production has emerged rapidly during the past decade.
      Today, two main research areas can be identified, one oriented toward the use of
      artificially introduced siRNAs for manipulation of gene expression, and the other
      one focused on the function of endogenous miRNAs. In both cases, the active
      molecule consists of a ~20-nucleotide-long RNA duplex. In the siRNA case,
      improved systemic stability is of central interest for its further development
      toward clinical applications. With respect to miRNA processing and function,
      understanding its influence on mRNA targeting and the silencing ability of
      individual miRNAs, e.g., under pathological conditions, remains a scientific
      challenge. In the present study, a model system is presented where the influence
      of the two clinically used anticancer drugs, cisplatin and oxaliplatin, on
      siRNA's silencing capacity has been evaluated. More specifically, siRNAs
      targeting the 3' UTR region of Wnt-5a mRNA (NM_003352) were constructed, and the
      biologically active antisense RNA strand was pre-platinated. Platinum adducts
      were detected and characterized by a combination of gel electrophoresis and MALDI
      MS techniques, and the silencing capacity was evaluated in cellular luciferase
      expressing systems using HB2 cells. Data show that platination of the antisense
      strand of the siRNAs results in adducts with protection against hydrolytic
      cleavage in the proximity of the platination sites, i.e., with altered
      degradation patterns compared to native RNAs. The MALDI-MS method was
      successfully used to further identify and characterize platinated RNA, with the
      naturally occurring platinum isotopic patterns serving as sensitive fingerprints
      for metalated sites. Expression assays all confirm biological activity of
      antisense-platinated siRNAs, here with platination sites located outside of the
      seed region. A significant reduction of silencing capacity was observed as a
      general trend, however. Of the two complexes studied, oxaliplatin exhibits the
      larger influence, thus indicating subtle differences between the abilities of cis
      and oxaliplatin to interfere with si- and miRNA processing.

PMID- 21721572
TI  - Self-templating polythiophene derivatives: electronic decoupling of conjugated
      strands through staggered packing.
AB  - Whereas molecular electronics needs well-controlled 3D geometries for decoupling
      or interconnecting individual molecules, conjugated polymers form disordered
      structures when deposited on a substrate. We show that this trend can be overcome
      in polythiophene derivatives designed so as to exploit weak sulfur-bromine
      interactions. A self-template effect follows, leading to staggered organizations
      of well-aligned electronically decoupled conjugated strands, as observed in situ
      by scanning tunneling microscopy and spectroscopy on graphite.

PMID- 21721573
TI  - Solvation structures of iodide on and below a surface of aqueous solution studied
      by photodetachment spectroscopy.
AB  - We investigated solvation structures of I(-) on and below a surface of an aqueous
      solution by photodetachment spectroscopy. An aqueous solution of an alkali halide
      was introduced to the vacuum as a continuous liquid flow (liquid beam), and the
      liquid beam was irradiated with a UV laser pulse. The intensity of electrons
      emitted from the surface by the laser excitation was measured as a function of
      wavelength (photodetachment spectroscopy), and we obtained absorption spectrum of
      I(-) on and below the solution surface. From the absorption spectrum, we found
      that I(-) starts to appear on the solution surface as the bulk NaI concentration
      increases. Similar concentration dependence was observed for the KI solution. We
      also found that I(-) located inside the solution is pushed to the surface, when
      NaCl is added to the solution. These changes are explained in terms of the
      difference in the polarizability of halide ions.

PMID- 21721574
TI  - Volatile composition of four southern highbush blueberry cultivars and effect of
      growing location and harvest date.
AB  - The volatile composition of four southern highbush blueberry cultivars
      ('Primadonna', 'Jewel', 'Snowchaser', and 'FL02-40') grown in two locations
      (Gainesville and Haines City, FL) and harvested multiple times was investigated.
      A total of 42 volatiles were identified, including 8 esters, 12 terpenoids, 11
      aldehydes, 7 alcohols, and 4 ketones. Twelve of these volatiles are reported for
      the first time in highbush blueberries, with 10 being positively identified: (Z)
      3-hexenal, (E,E)-2,4-hexadienal, (E,Z)-2,6-nonadienal, (E,E)-2,4-nonedienal,
      methyl 2-methylbutanoate, butyl acetate, 2-methylbutyl acetate, and geranyl
      acetate. The dominant volatiles were aldehydes followed by terpenoids and esters,
      with distinct varietal profiles. 'Primadonna' was characterized by a large amount
      of esters and C-6 aldehydes. In contrast, fewer than 4 esters were found in 'FL02
      40' and 'Snowchaser', respectively, but they produced more terpenoids than
      'Primadonna' and 'Jewel'. Location and/or harvest date affected the production of
      volatiles in 'Primadonna', but not so much in the other cultivars.

PMID- 21721575
TI  - Acrylamide formation in almonds (Prunus dulcis): influences of roasting time and
      temperature, precursors, varietal selection, and storage.
AB  - Acrylamide is a probable human carcinogen that is found in many roasted and baked
      foods. This paper describes two sensitive and reliable LC-(ESI)MS/MS methods for
      the analysis of (1) acrylamide and (2) common acrylamide precursors (i.e.,
      glucose, fructose, asparagine, and glutamine) in raw and roasted almonds. These
      methods were used to evaluate the impact of roasting temperatures (between 129
      and 182  degrees C) and times on acrylamide formation. Controlling the roasting
      temperature at or below 146  degrees C resulted in acrylamide levels below 200
      ppb at all roasting times evaluated. Six varieties of almonds collected in
      various regions of California over two harvest years and roasted at 138  degrees
      C for 22 min had acrylamide levels ranging from 117 +/- 5 MUg/kg (Sonora) to 221
      +/- 95 MUg/kg (Butte) with an average of 187 +/- 71 MUg/kg. A weak correlation
      between asparagine content in raw almonds and acrylamide formation was observed
      (R(2) = 0.6787). No statistical relationship was found between acrylamide
      formation and almond variety, orchard region, or harvest year. Stability studies
      on roasted almonds indicated that acrylamide levels decreased by 12.9-68.5%
      (average of 50.2%) after 3 days of storage at 60  degrees C. Short-term elevated
      temperature storage may be another approach for mitigating acrylamide levels in
      roasted almonds.

PMID- 21721576
TI  - New dialkyldithiophosphinic acid self-assembled monolayers (SAMs): influence of
      gold substrate morphology on adsorbate binding and SAM structure.
AB  - We report the fabrication and characterization of new self-assembled monolayers
      (SAMs) formed from dihexadecyldithiophosphinic acid [(C(16))(2)DTPA] molecules on
      gold substrates. In these SAMs, the ability of the (C(16))(2)DTPA headgroup to
      chelate to the gold surface depends on the morphology of the gold substrate. Gold
      substrates fabricated by electron-beam evaporation (As-Dep gold) consist of ~50
      nm grains separated by deep grain boundaries (~10 nm). These grain boundaries
      inhibit the chelation of (C(16))(2)DTPA adsorbates to the surface, producing SAMs
      in which there is a mixture of monodentate and bidentate adsorbates. In contrast,
      gold substrates produced by template stripping (TS gold) consist of larger grains
      (~200-500 nm) with shallower grain boundaries (<2 nm). On these substrates, the
      low density of shallow grain boundaries allows (C(16))(2)DTPA molecules to
      chelate to the surface, producing SAMs in which all molecules are bidentate. The
      content of bidentate adsorbates in (C(16))(2)DTPA SAMs formed on As-Dep and TS
      gold substrates strongly affects the SAM properties: Alkyl chain organization,
      wettability, frictional response, barrier properties, thickness, and thermal
      stability all depend on whether a SAM has been formed on As-Dep or TS gold. This
      study demonstrates that substrate morphology has an important influence on the
      structure of SAMs formed from these chelating adsorbates.

PMID- 21721577
TI  - Surface modification of luminescent lanthanide phosphate nanorods with cationic
      "Quat-primer" polymers.
AB  - "Quat-primer" polymers bearing cationic groups were investigated as a surface
      modifier for Tb-doped cerium phosphate green-emitting fluorescent nanorods (NRs).
      The NRs were synthesized by a microwave process without using any complex agents
      or ligands and were characterized with different analytical tools such as X-ray
      diffraction, transmission electron microscopy, and fluorescence spectroscopy.
      Poly(ethyleneimine) partially quarternized with glycidyltrimethylammonium
      chloride was synthesized separately and characterized in detail. (1)H and (13)C
      NMR spectroscopic studies revealed that the quaternary ammonium group was
      covalently attached to the polymer. UV-vis spectroscopy was used to examine the
      stability of the colloidal dispersions of the bare NRs as well as the modified
      NRs. zeta potential, thermogravimetric analysis, and atomic force microscopy
      studies were carried out to confirm that the positively charged Quat-primer
      polymer is adsorbed on the negatively charged surface of the NRs, which results
      in high dispersion stability. Emission spectra of the modified NRs indicated that
      there was no interference of the Quat-primer polymer with the fluorescence
      behavior.

PMID- 21721578
TI  - Adsorption of PEO-PPO-PEO triblock copolymers with end-capped cationic chains of
      poly(2-dimethylaminoethyl methacrylate).
AB  - We study the adsorption of a symmetric triblock copolymer of ethylene oxide, EO,
      and propylene oxide, PO, end-capped with quarternized poly(2-dimethylaminoethyl
      methacrylate), DMAEMA (DMAEMA(24)-EO(132)PO(50)EO(132)-DMAEMA(24)). Light
      scattering and tensiometry are used to measure the relative size of the
      associated structures and surface excess at the air-liquid interface. The
      adsorbed amount, the amount of coupled water, and the viscoelasticity of the
      adsorbed polymer layer are measured on hydrophobic and hydrophilic surfaces
      (polypropylene, cellulose, and silica) by using quartz crystal microgravimetry
      (QCM) and surface plasmon resonance (SPR) at different ionic strengths and
      temperatures. The results of the experiments are compared with those obtained
      after adsorption of the uncharged precursor copolymer, without the cationic end
      caps (EO(132)PO(50)EO(132)). DMAEMA(24)-EO(132)PO(50)EO(132)-DMAEMA(24) possesses
      higher affinity with the negatively charged silica and cellulose surfaces while
      the uncharged copolymer adsorbs to a larger extent on polypropylene surfaces. In
      this latter case, adsorption increases with increasing solution ionic strength
      and temperature. Adsorption of EO(132)PO(50)EO(132) on silica surfaces has little
      effect on the water contact angle (WCA), while adsorption of DMAEMA(24)
      EO(132)PO(50)EO(132)-DMAEMA(24) increases the WCA of silica to 32 degrees ,
      indicating a large density of exposed PPO blocks upon adsorption. After
      adsorption of EO(132)PO(50)EO(132) and DMAEMA(24)-EO(132)PO(50)EO(132)-DMAEMA(24)
      on PP, the WCA is reduced by ~14 degrees  and ~28 degrees , respectively, due to
      the exposed hydrophilic EO and highly water-soluble DMAEMA segments on the
      surfaces. The extent of surface coverage at saturation at the
      polypropylene/liquid interfaces (~31 and 40 nm(2)/molecule obtained by QCM and
      SPR, respectively) is much lower, as expected, when compared with results
      obtained at the air/liquid interface, where a tighter packing is observed. The
      percentage of water coupled to the adsorbed cationic polymer decreases with
      solution ionic strength. Overall, these observations are ascribed to the effects
      of electrostatic screening, polymer hydrodynamic size, and solvency.

PMID- 21721579
TI  - Antioxidant properties of green tea extract protect reduced fat soft cheese
      against oxidation induced by light exposure.
AB  - The effect of two different antioxidants, EDTA and green tea extract (GTE), used
      individually or in combination, on the light-induced oxidation of reduced fat
      soft cheeses (0.2 and 6% fat) was investigated. In samples with 0.2% fat, lipid
      hydroperoxides as primary lipid oxidation products were not detected, but their
      interference was suggested from the formation of secondary lipid oxidation
      products such as hexanal and heptanal. The occurrence of these oxidation markers
      was inhibited by spiking with 50 ppm EDTA or 750 ppm GTE, or a combination of the
      two prior to irradiation. In contrast, addition of 50 ppm EDTA to samples with 6%
      fat was ineffective, but 750 ppm GTE (alone or in combination with EDTA) strongly
      reduced levels of hexanal and heptanal. Accumulation of primary lipid
      hydroperoxides was not affected by GTE, hence antioxidative activity was ascribed
      to scavenging of hexanal and heptanal precursors. These radical intermediates
      result from hydroperoxide disintegration, and subsequent scavenging by GTE, which
      acts as a radical sink, corroborates the intense signal observed by electron
      paramagnetic resonance (EPR) spectroscopy.

PMID- 21721580
TI  - Controlling adhesion force by means of nanoscale surface roughness.
AB  - Control of adhesion is a crucial aspect in the design of microelectromechanical
      and nanoelectromechanical devices. To understand the dependence of adhesion on
      nanometer-scale surface roughness, a roughness gradient has been employed.
      Monomodal roughness gradients were fabricated by means of silica nanoparticles
      (diameter ~12 nm) to produce substrates with varying nanoparticle density. Pull
      off force measurements on the gradients were performed using (polyethylene)
      colloidal-probe microscopy under perfluorodecalin, in order to restrict
      interactions to van der Waals forces. The influence of normal load on pull-off
      forces was studied and the measured forces compared with existing Hamaker
      approximation-based models. We observe that adhesion force reaches a minimum
      value at an optimum particle density on the gradient sample, where the mean
      particle spacing becomes comparable with the diameter of the contact area with
      the polyethylene sphere. We also observe that the effect on adhesion of
      increasing the normal load depends on the roughness of the surface.

PMID- 21721581
TI  - Caveolin-1 is a competitive inhibitor of heme oxygenase-1 (HO-1) with heme:
      identification of a minimum sequence in caveolin-1 for binding to HO-1.
AB  - Heme oxygenase (HO) catalyzes the O(2)-dependent degradation of heme to
      biliverdin IXalpha, carbon monoxide (CO), and free ferrous iron through a
      multistep mechanism. Electrons required for HO catalysis in mammals are provided
      by NADPH-cytochrome P450 reductase. Recently, Kim et al. reported for the first
      time that HO, especially inducible HO-1, appears in caveolae and showed that
      caveolin-1, a principal isoform of the caveolin family, physically interacts with
      HO-1 [ Jung , N. H. et al. ( 2003 ) IUBMB Life 55 , 525 - 532 ; Kim , H. P. et
      al. ( 2004 ) FASEB J. 18 , 1080 - 1089 ]. In the present study, we confirmed by
      immunoprecipitation experiments that rat HO-1 and rat caveolin-1 (residues 1-101)
      directly interact with each other and that the HO-1 activity is inhibited by
      caveolin-1 (1-101). The 82-101 residues of caveolin-1 (CAV(82-101)), called the
      caveolin scaffolding domain, play essential roles in caveolin-related protein
      protein interactions. The HO-1 activity is also inhibited by CAV(82-101) in a
      competitive manner with hemin, and a hemin titration experiment showed that
      CAV(82-101) interferes with hemin binding to HO-1. The enzyme kinetics and
      surface plasmon resonance experiments gave comparable K(i) and K(D) values of 5.2
      and 1.0 MUM for CAV(82-101), respectively, with respect to the interaction with
      HO-1. These observations indicated that CAV(82-101) and hemin share a common
      binding site within the HO-1 protein. The identified caveolin binding motif
      (FLLNIELF) of rat HO-1 is incomplete compared to the proposed consensus sequence.
      The affinity between HO-1 and CAV(82-101), however, was almost completely or
      remarkably eliminated by replacement of Phe(207) and/or Phe(214) with Ala,
      indicating that HO-1 binds to caveolin-1 via this motif. Among the peptide
      fragments derived from CAV(82-101), i.e., CAV(82-91), CAV(87-96), CAV(92-101),
      and CAV(97-101), CAV(92-101) and CAV(97-101) are able to inhibit the HO-1
      activity to a similar extent; thus, the five-amino acid sequence (residues 97
      101) is considered to be a minimum sequence for binding to HO-1.

PMID- 21721582
TI  - Excess thermodynamic properties of mixtures involving xenon and light alkanes: a
      study of their temperature dependence by computer simulation.
AB  - As a natural extension of a previous work, excess molar enthalpies and excess
      molar volumes as a function of composition in a wide range of temperatures have
      been obtained for binary mixtures of xenon with ethane, propane, and n-butane by
      Monte Carlo computer simulation. Xenon was modeled by a simple spherical Lennard
      Jones potential, and the TraPPE-UA force field was used to describe the n
      alkanes. One of the main goals of this study is to investigate the temperature
      dependence of the excess properties for mixtures of xenon and n-alkanes and, if
      possible, to supplement the lack of experimental data. For all three systems, the
      simulation results predicted excess volumes in good agreement with the
      experimental data. As for the excess enthalpies, in the case of (xenon + ethane),
      the simulation results confirm the negative experimental result and the weak
      temperature dependence. In the case of (xenon + propane) and (xenon + n-butane),
      however, the simulation predicts negative excess enthalpies, but those estimated
      from experimental data are positive. Both excess volumes and enthalpies display a
      complex dependence on temperature that in some aspects resembles that found for
      mixtures of n-alkanes.The structure of the liquid mixtures was also investigated
      by calculating radial distribution functions [g(alphabeta)(r)] between each pair
      of interaction groups for all the binary systems at all temperatures. It is found
      that the mean distance between xenon and CH(2) groups is systematically higher
      than the distance between xenon and CH(3). In addition, the number of groups
      around xenon in the first coordination sphere was calculated and seems to be
      proportionally more populated by methyl groups than by methylene groups. The
      results seem to reflect a preferential and stronger interaction between xenon and
      CH(3), in agreement with previous findings.

PMID- 21721583
TI  - Nonlinear charge transport in redox molecular junctions: a Marcus perspective.
AB  - Redox molecular junctions are molecular conduction junctions that involve more
      than one oxidation state of the molecular bridge. This property is derived from
      the ability of the molecule to transiently localize transmitting electrons,
      implying relatively weak molecule-leads coupling and, in many cases, the validity
      of the Marcus theory of electron transfer. Here we study the implications of this
      property on the nonlinear transport properties of such junctions. We obtain an
      analytical solution of the integral equations that describe molecular conduction
      in the Marcus kinetic regime and use it in different physical limits to predict
      some important features of nonlinear transport in metal-molecule-metal junctions.
      In particular, conduction, rectification, and negative differential resistance
      can be obtained in different regimes of interplay between two different
      conduction channels associated with different localization properties of the
      excess molecular charge, without specific assumptions about the electronic
      structure of the molecular bridge. The predicted behaviors show temperature
      dependences typically observed in the experiment. The validity of the proposed
      model and ways to test its predictions and implement the implied control
      strategies are discussed.

PMID- 21721584
TI  - Food matrix effects on in vitro digestion of microencapsulated tuna oil powder.
AB  - Tuna oil, containing 53 mg of eicosapentaenoic acid (EPA) and 241 mg of
      docosahexaenoic acid (DHA) per gram of oil, delivered as a neat microencapsulated
      tuna oil powder (25% oil loading) or in food matrices (orange juice, yogurt, or
      cereal bar) fortified with microencapsulated tuna oil powder was digested in
      simulated gastric fluid or sequentially in simulated gastric fluid and simulated
      intestinal fluid. The level of fortification was equivalent to 1 g of tuna oil
      per recommended serving size (i.e., per 200 g of orange juice or yogurt or 60 g
      of cereal bar). The changes in particle size of oil droplets during digestion
      were influenced by the method of delivery of the microencapsulated tuna oil
      powder. Lipolysis in simulated gastric fluid was low, with only 4.4-6.1% EPA and
      <=1.5% DHA released after digestion (as a % of total fatty acids present). After
      sequential exposure to simulated gastric and intestinal fluids, much higher
      extents of lipolysis of both glycerol-bound EPA and DHA were obtained (73.2-78.6%
      for the neat powder, fortified orange juice, and yogurt; 60.3-64.0% for the
      fortified cereal bar). This research demonstrates that the choice of food matrix
      may influence the lipolysis of microencapsulated tuna oil.

PMID- 21721585
TI  - Allium species from Central and Southwest Asia are rich sources of marasmin.
AB  - Marasmin, which is especially known from the two South African species Tulbaghia
      alliacea and Tulbaghia violacea , but was also described for the garlic mushroom
      Marasmius alliaceus , is the precursor of the thiosulfinate marasmicin.
      Marasmicin has attracted considerable attention because of its antifungal and
      tuberculostatic activities. However, many Allium species of the subgenus
      Melanocrommyum, especially Allium suworowii , are also very rich in marasmin. A.
      suworowii revealed concentrations of marasmin up to 1.6%, related to the fresh
      weight of bulbs, and up to 3.0%, related to air-dried fruiting bodies, of the
      corresponding gamma-glutamylmarsmin was found in M. alliaceus. Both species show
      much higher amounts of marasmin as Tulbaghia and could be considered as natural
      sources for the isolation of this compound. Further promising Allium species with
      considerable amounts of marasmin besides other cysteine sulfoxides are Allium
      stipitatum and Allium altissimum . (R(S),R(C))-Marasmin is typical for the
      investigated species of the subgenus Melanocrommyum, whereas gamma-glutamyl
      (S(S),R(C))-marasmin is the only cysteine sulfoxide for the genus Marasmius known
      until now. Both cysteine sulfoxides were isolated and described as o
      phthaldialdehyde (OPA) derivatives. Furthermore, the cysteine sulfoxides methiin,
      propiin, S-(2-pyrrolyl)-cysteine sulfoxide, eventually S-(2-pyridyl)-cysteine
      sulfoxide and S-(2-pyridyl)-L-cysteine N-oxide were found.

PMID- 21721586
TI  - Controlling conformational flexibility of an O2-binding H-NOX domain.
AB  - Heme Nitric oxide/OXygen binding (H-NOX) domains have provided a novel scaffold
      to probe ligand affinity in hemoproteins. Mutation of isoleucine 5, a conserved
      residue located in the heme-binding pocket of the H-NOX domain from
      Thermoanaerobacter tengcongensis (Tt H-NOX), was carried out to examine changes
      in oxygen (O(2))-binding properties. A series of I5 mutants (I5F, I5F/I75F,
      I5F/L144F, I5F/I75F/L144F) were investigated to probe the role of steric bulk
      within the heme pocket. The mutations significantly increased O(2) association
      rates (1.5-2.5-fold) and dissociation rates (8-190-fold) as compared to wild-type
      Tt H-NOX. Structural changes that accompanied the I5F mutation were characterized
      using X-ray crystallography and resonance Raman spectroscopy. A 1.67 A crystal
      structure of the I5F mutant indicated that introducing a phenylalanine at
      position 5 resulted in a significant shift of the N-terminal domain of the
      protein, causing an opening of the heme pocket. This movement also resulted in an
      increased amount of flexibility at the N-terminus and the loop covering the N
      terminal helix as indicated by the two conformations of the first six N-terminal
      amino acids, high B-factors in this region of the protein, and partially
      discontinuous electron density. In addition, introduction of a phenylalanine at
      position 5 resulted in increased flexibility of the heme within the pocket and
      weakened hydrogen bonding to the bound O(2) as measured by resonance Raman
      spectroscopy. This study provides insight into the critical role of I5 in
      controlling conformational flexibility and ligand affinity in H-NOX proteins.

PMID- 21721587
TI  - Regioselective synthesis of isochromenones by iron(III)/PhSeSePh-mediated
      cyclization of 2-alkynylaryl esters.
AB  - A series of 4-Se-(Te, S)-isochromenones and 3-substituted isochromenones were
      synthesized in good yields via FeCl(3)-mediated cyclization of alkynylaryl esters
      with different diorganyl dichalcogenides. This methodology was carried out at
      room temperature, using inexpensive and environmentally friendly iron salts as
      metallic source and under air atmosphere. The reaction showed to be tolerant to a
      range of substituents bonded into the aromatic ring of the diorganyl
      dichalcogenides as well as to alkyl groups directly bonded to the chalcogen atom.
      Alternatively, the cyclization reaction of 2-alkynylaryl esters with FeCl(3), in
      the absence of diorganyl dichalcogenide, gave the isochromenones without the
      chalcogen moiety in the structure. This approach proved to be highly
      regioselective, providing only six-membered ring products, once the possible five
      membered products were not observed in any experiments.

PMID- 21721588
TI  - Tofu (soybean curd) lowers serum lipid levels and modulates hepatic gene
      expression involved in lipogenesis primarily through its protein, not isoflavone,
      component in rats.
AB  - Although soy foods are recommended to prevent hyperlipidemia and related
      diseases, it is unclear how their active ingredients exert their effects. Here,
      the effects of tofu (soybean curd) and its putative active components, protein
      and isoflavone, on lipid metabolism in male rats were compared. Tofu and soy
      protein significantly lowered serum triacylglycerol and cholesterol levels
      compared to casein and, through microarray analyses, were found to exclusively
      alter transcriptomes involved in fatty acid and/or steroid synthesis in the
      liver, where most of the serum lipids are synthesized. In contrast, isoflavone
      supplementation had little effect on serum lipid levels or gene expression and
      exerted no synergistic effects with soy protein or tofu. The importance of the
      proteinaceous components was further confirmed by the lower activity of enzymes
      involved in lipogenesis. From these findings it was concluded that the protein,
      not isoflavone, fraction of soy reduces lipogenesis in liver through gene
      expression and that this may result in lower serum lipid levels.

PMID- 21721589
TI  - Luteolin inhibits the release of glutamate in rat cerebrocortical nerve
      terminals.
AB  - The present study investigated the effect and possible mechanism of luteolin, a
      food-derived flavonoid, on endogenous glutamate release in nerve terminals of rat
      cerebral cortex (synaptosomes). Luteolin inhibited the release of glutamate
      evoked by the K(+) channel blocker 4-aminopyridine (4-AP), and this phenomenon
      was concentration-dependent. The effect of luteolin on the evoked glutamate
      release was prevented by the chelation of the extracellular Ca(2+) ions and by
      the vesicular transporter inhibitor, but was insensitive to the glutamate
      transporter inhibitor. Luteolin decreased the 4-AP-induced increase in
      [Ca(2+)](C), whereas it did not alter 4-AP-mediated depolarization. Furthermore,
      the effect of luteolin on evoked glutamate release was abolished by blocking the
      Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking the
      ryanodine receptors or the mitochondrial Na(+)/Ca(2+) exchange. In addition, the
      inhibitory effect of luteolin on evoked glutamate release was prevented by the
      mitogen-activated/extracellular signal-regulated kinase (MEK) inhibitors. Western
      blot analyses showed that luteolin decreased the 4-AP-induced phosphorylation of
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synapsin I, the main
      presynaptic target of ERK. Thus, it was concluded that luteolin inhibits
      glutamate release from rat cortical synaptosomes through the suppression of
      presynaptic voltage-dependent Ca(2+) entry and MEK/ERK signaling cascade.

PMID- 21721590
TI  - Cycle control and bleeding pattern of a 24/4 regimen of drospirenone 3
      mg/ethinylestradiol 20 MUg compared with a 21/7 regimen of desogestrel 150
      MUg/ethinylestradiol 20 MUg: a pooled analysis.
AB  - BACKGROUND AND OBJECTIVE: The degree of cycle control achieved with a hormonal
      contraceptive method is an important determinant of its acceptance and
      continuation. This study set out to compare the cycle control and bleeding
      profile of drospirenone (DRSP) 3 mg/ethinylestradiol (EE) 20 MUg in a 24-active
      pill/4-inert pill (24/4) regimen (YAZ(r)) with those of desogestrel (DSG) 150
      MUg/EE 20 MUg in a 21/7 regimen (Mercilon(r)), an established European combined
      oral contraceptive (COC). METHODS: Bleeding data from women aged 17-36 years who
      received either DRSP 3 mg/EE 20 MUg in a 24/4 regimen (n = 1285) or DSG 150
      MUg/EE 20 MUg in a 21/7 regimen (n = 471) during four clinical studies were
      pooled and analysed over seven treatment cycles. RESULTS: The maximum intensity
      of scheduled withdrawal bleeding was 'normal bleeding' for >50% of subjects in
      cycles 1-6 in both treatment groups. Moreover, the incidence of unscheduled
      intracyclic bleeding during cycles 2-7 was comparable between treatment types
      (10.2-14.9% in women treated with DRSP 3 mg/EE 20 MUg 24/4 vs 8.6-13.8% in women
      treated with DSG 150 MUg/EE 20 MUg 21/7). Overall, similar bleeding patterns were
      observed with both treatments. CONCLUSION: DRSP 3 mg/EE 20 MUg 24/4 is associated
      with a bleeding profile and cycle control that is comparable to that of an
      established, low-dose COC formulation.

PMID- 21721591
TI  - Pharmacokinetics of oxybutynin chloride topical gel: effects of application site,
      baths, sunscreen and person-to-person transference.
AB  - BACKGROUND: Oxybutynin chloride topical gel (OTG; Gelnique(r)) is an approved
      formulation for the transdermal administration of oxybutynin, an established
      antimuscarinic therapy for overactive bladder (OAB). Transdermal administration
      of oxybutynin minimizes plasma concentrations of the active metabolite N
      desethyloxybutynin (N-DEO), which can have anticholinergic adverse effects.
      OBJECTIVES: In four phase I studies, we separately assessed the effects of OTG
      application site selection on oxybutynin bioavailability (site-to-site study);
      the effects of post-application showering on oxybutynin steady-state
      pharmacokinetics (showering study); the effects of sunscreen application on
      oxybutynin absorption (sunscreen study); and the person-to-person transfer of
      oxybutynin through skin-to-skin contact at the application site (transference
      study). METHODS: All four studies were open-label, randomized, phase I studies.
      The site-to-site and showering studies involved repeated administration of OTG to
      establish steady-state plasma concentrations of oxybutynin and N-DEO; the other
      two studies involved single doses. Clinical visits were required for
      pharmacokinetic sampling, supervision of OTG self-application on pharmacokinetic
      sampling days, showering, sunscreen application and transference experiments. The
      study included healthy subjects aged 18-45 years. Subjects with conditions
      requiring medical therapy or interfering with the application of OTG or the
      interpretation of pharmacokinetic results were excluded. Participants applied OTG
      (1 g containing oxybutynin chloride 10%, 1.14 mL/dose) once daily to the abdomen,
      upper arm/shoulder or thigh. Showering occurred 1-6 hours after dosing. Sunscreen
      was applied 30 minutes before or after OTG application. Abdomen-to-abdomen
      contact with movement for 15 minutes between treated and untreated participants
      was conducted 1 hour after dosing. Time points of serial blood sampling for
      pharmacokinetic analyses varied among studies. Plasma concentrations of
      oxybutynin and N-DEO (except transference study) were measured. Bioequivalence
      was tested with ANOVA models for log(e)-transformed plasma exposure (area under
      the plasma concentration-time curve [AUC]) and maximum plasma concentration
      (C(max)) to generate 90% confidence intervals (CIs). RESULTS: Oxybutynin and N
      DEO exposures (AUCs) from time zero to 24 hours (AUC(24)) were similar for the
      three application sites, with N-DEO/oxybutynin mean AUC(24) ratios of
      approximately 0.9. The 90% CIs for thigh-to-abdomen ratios of oxybutynin AUC(24)
      (0.93, 1.23) and C(max) (0.85, 1.16) were within the interval required for
      bioequivalence (0.8, 1.25); the other application site ratios for oxybutynin had
      boundaries slightly outside this interval. Showering 1-6 hours and sunscreen
      application 30 minutes before or after OTG application had minor effects on
      oxybutynin concentrations. After vigorous skin contact between treated and
      untreated participants at the application site, the mean +/- SD AUC from time
      zero to 48 hours (AUC(48)) of oxybutynin in 12 untreated participants was 29.8 +/
      24.5 ng . h/mL, approximately one-quarter of the exposures generally seen in
      subjects treated with a single dose of OTG. Oxybutynin AUC(48) after clothing-to
      skin contact was undetectable in 12 of 14 untreated participants and very low
      (mean +/- SD 0.4 +/- 0.8 ng . h/mL) in two untreated female participants.
      CONCLUSION: The bioavailability of oxybutynin and its pharmacokinetic profile are
      not greatly affected by application site selection, post-application showering or
      sunscreen use shortly before or after dosing with OTG. Oxybutynin transference to
      untreated persons is essentially prevented by avoiding direct skin-to-skin
      contact with the application site.

PMID- 21721593
TI  - Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral
      contraceptive: a randomized, open-label, single-centre study.
AB  - BACKGROUND AND OBJECTIVE: The hormonal components of combined oral contraceptives
      (COCs) have various metabolic and haemostatic effects. The objective of this
      study was to compare the metabolic and haemostatic effects of a novel COC
      comprising estradiol valerate/dienogest (E(2)V/DNG) with
      ethinylestradiol/levonorgestrel (EE/LNG). METHODS: In a randomized, open-label
      study conducted in Germany over seven cycles, healthy women aged 18-50 years
      received E(2)V/DNG (E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7,
      E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26, placebo on days 27
      28; n = 30) or EE/LNG (EE 0.03 mg/LNG 0.05 mg on days 1-6, EE 0.04 mg/LNG 0.075
      mg on days 7-11, EE 0.03 mg/LNG 0.125 mg on days 12-21, placebo on days 22-28; n
      = 28). The primary variables were the mean intraindividual relative changes from
      baseline to cycle 7 in high-density lipoprotein (HDL) and low-density lipoprotein
      (LDL) cholesterol levels. Changes in other lipid parameters, haemostatic
      parameters, sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG),
      carbohydrate metabolism parameters, blood pressure and body weight were also
      assessed. RESULTS: Mean +/- SD HDL cholesterol increased by 7.9% +/- 21.8% with
      E(2)V/DNG and decreased by 2.3% +/- 14.4% with EE/LNG. Mean +/- SD LDL
      cholesterol decreased by 6.5% +/- 15.9% with E(2)V/DNG and by 3.0% +/- 17.4% with
      EE/LNG. Mean +/- SD prothrombin fragment 1 + 2 and D-dimer levels remained
      essentially unchanged in the E(2)V/DNG group (-0.6% +/- 30.3% and -2.1% +/-
      43.5%, respectively), but increased in the EE/LNG group (by 117.3% +/- 358.0% and
      62.9% +/- 99.5%, respectively). Changes in other hepatic-induced parameters
      (SHBG, CBG) and carbohydrate metabolism were generally less pronounced with
      E(2)V/DNG versus EE/LNG. Body weight and blood pressure remained stable
      throughout the study in both treatment groups. Both formulations were well
      tolerated, with no serious adverse events reported. CONCLUSION: E(2)V/DNG had a
      minimal impact on metabolic and haemostatic parameters, and a more favourable
      effect than EE/LNG on lipid markers. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT00185224.

PMID- 21721594
TI  - Pharmacokinetics of diazepam administered intramuscularly by autoinjector versus
      rectal gel in healthy subjects: a phase I, randomized, open-label, single-dose,
      crossover, single-centre study.
AB  - BACKGROUND AND OBJECTIVE: Acute repetitive seizures (ARS) are a debilitating part
      of episodic seizure activity that can sometimes progress to status epilepticus.
      Currently approved treatment that can be administered by non-medical personnel to
      patients with ARS is a diazepam rectal gel. While effective, rectal
      administration can be difficult, inconvenient and objectionable. A diazepam
      autoinjector has been developed to deliver diazepam via an intramuscular (IM)
      injection. This study evaluated the dose proportionality of the diazepam
      autoinjector and the consequent diazepam bioavailability relative to an
      equivalent dose of diazepam administered rectally as a commercial gel. METHODS:
      This was a phase I, randomized, open-label, two-part, single-dose, crossover,
      single-centre pharmacokinetic study in 48 healthy young adult (aged 18-40 years)
      male and female subjects. Part I of the study (n = 24) evaluated the dose
      proportionality of three strengths of the diazepam autoinjector (5, 10 and 15 mg)
      administered into the mid-outer thigh via a deep IM injection. Part II (n = 24)
      assessed the relative bioavailability of the diazepam 10 mg autoinjector versus
      the diazepam 10 mg rectal gel. Parts I and II were run concurrently. Each subject
      completed screening up to 30 days prior to three (Part I) or two (Part II) dosing
      periods. Serial blood sampling for plasma diazepam and desmethyldiazepam
      (metabolite) concentrations, vital signs and adverse event (AE) assessments were
      performed at prespecified times. Treatments were separated by a 14-day washout
      period. RESULTS: In Part I, dose proportionality was demonstrated for the
      diazepam autoinjector at 5, 10 and 15 mg doses by increases in mean maximum
      plasma concentration (C(max)), mean area under the plasma concentration-time
      curve (AUC) from time zero to infinity (AUC(infinity)), and mean AUC from time
      zero to time of last measurable concentration (AUC(last)). The median time to
      reach C(max) (t(max)) was consistent at 1 hour for each dose. In Part II of the
      study, IM administration via diazepam autoinjector (10 mg) resulted in plasma
      concentrations of both diazepam and desmethyldiazepam that were slightly higher
      and less variable than those observed following administration of diazepam rectal
      gel (10 mg). The geometric mean ratio (diazepam autoinjector/diazepam rectal gel)
      and 90% confidence intervals for diazepam C(max) and AUC(last) were 0.94 (0.84,
      1.05) and 1.14 (1.08, 1.21), respectively, indicating that the overall
      bioavailability of the diazepam autoinjector was approximately 14% higher than
      that of diazepam rectal gel. Both treatments were generally well tolerated.
      Although the incidence of treatment-emergent AEs was higher with diazepam
      autoinjector compared with diazepam rectal gel (21.7% vs 13.6%), the difference
      can be attributed to injection site pain. Injection site pain also correlated
      with the diazepam autoinjector dose administered in Part I: 5 mg (4.3%), 10 mg
      (21.7%) and 15 mg (27.3%). However, no patients discontinued the trial due to
      injection site pain. No other AEs correlated with dose, and there was no evidence
      of respiratory depression with either administration. CONCLUSION: Results of the
      present study indicated that diazepam can be safely and reliably administered IM
      using a diazepam autoinjector.

PMID- 21721596
TI  - Polypharmacy in the elderly: can comprehensive geriatric assessment reduce
      inappropriate medication use?
AB  - Polypharmacy is a problem of growing interest in geriatrics with the increase in
      drug consumption in recent years, particularly among people aged >65 years. The
      main reasons for polypharmacy are longer life expectancy, co-morbidity and the
      implementation of evidence-based clinical practice guidelines. However,
      polypharmacy also has important negative consequences, such as a higher risk of
      adverse drug reactions and a decline in medication efficacy because of reduced
      compliance. Comprehensive geriatric assessment (CGA) has proved effective in
      reducing the number of prescriptions and daily drug doses for patients by
      facilitating discontinuation of unnecessary or inappropriate medications. CGA has
      also demonstrated an ability to optimize treatment by increasing the number of
      drugs taken in cases where under-treatment has been identified. Greater
      multidimensional and multidisciplinary efforts are nonetheless needed to tackle
      polypharmacy-related problems in frail elderly patients. CGA should help
      geriatrics staff identify diseases with higher priority for treatment, thereby
      achieving better pharmacological treatment overall in elderly patients. The
      patient's prognosis should also be considered in the treatment prioritization
      process. The most appropriate medication regimen should combine existing evidence
      based clinical practice guidelines with data gathered from CGA, including social
      and economic considerations. Furthermore, for prescriptions to remain
      appropriate, the elderly should periodically undergo medication review,
      particularly as the risk or presence of multiple co-morbidities increases. This
      article aims to highlight the increasing impact of polypharmacy in the elderly
      and to underscore the role of CGA in achieving the most appropriate
      pharmacological treatment in this age group.

PMID- 21721598
TI  - Combination therapy for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, degenerative brain disease. The
      mainstay of current management of patients with AD involves drugs that provide
      symptomatic therapy. Two classes of medications have been approved by the US FDA
      for the treatment of AD: the cholinesterase inhibitors (ChEIs), which include
      galantamine and rivastigmine (both approved for use in mild to moderate AD) and
      donepezil (approved for use in mild to severe AD); and the non-competitive NMDA
      receptor antagonist memantine (approved for use in moderate to severe AD). The
      European and Asian regulatory bodies have also approved ChEIs as monotherapy in
      mild to moderate AD. Future research directions are mostly focusing on disease
      modification and prevention. This review covers key studies of the efficacy,
      safety and tolerability of combination therapy in AD, defined as a combination of
      the NMDA receptor antagonist memantine with any of the ChEIs (donepezil,
      galantamine or rivastigmine) for the treatment of AD. Relevant studies were
      identified via a PubMed search. This review shows that combination therapy for AD
      seems to be safe, well tolerated and may represent the current gold standard for
      treatment of moderate to severe AD and possibly mild to moderate AD as well.

PMID- 21721597
TI  - Elderly patients with community-acquired pneumonia: optimal treatment strategies.
AB  - Community-acquired pneumonia (CAP) is a common infectious disease that still
      causes substantial morbidity and mortality. Elderly people are frequently
      affected, and several issues related to care of this condition in the elderly
      have to be considered. This article reviews current recommendations of guidelines
      with a special focus on aspects of the care of elderly patients with CAP. The
      most common pathogen in CAP is still Streptococcus pneumoniae, followed by other
      pathogens such as Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila
      pneumoniae and Legionella species. Antimicrobial resistance is an increasing
      problem, especially with regard to macrolide-resistant S. pneumoniae and
      fluoroquinolone-resistant strains. With regard to beta-lactam antibacterials,
      resistance by H. influenzae and Moraxella catarrhalis is important, as is the
      emergence of multidrug-resistant Staphylococcus aureus. The main management
      decisions should be guided by the severity of disease, which can be assessed by
      validated clinical risk scores such as CURB-65, a tool for measuring the severity
      of pneumonia based on assessment of confusion, serum urea, respiratory rate and
      blood pressure in patients aged >=65 years. For the treatment of low-risk
      pneumonia, an aminopenicillin such as amoxicillin with or without a beta
      lactamase inhibitor is frequently recommended. Monotherapy with macrolides is
      also possible, although macrolide resistance is of concern. When predisposing
      factors for special pathogens are present, a beta-lactam antibacterial combined
      with a beta-lactamase inhibitor, or the combination of a beta-lactam
      antibacterial, a beta-lactamase inhibitor and a macrolide, may be warranted. If
      possible, patients who have undergone previous antibacterial therapy should
      receive drug classes not previously used. For hospitalized patients with non
      severe pneumonia, a common recommendation is empirical antibacterial therapy with
      an aminopenicillin in combination with a beta-lactamase inhibitor, or with
      fluoroquinolone monotherapy. With proven Legionella pneumonia, a combination of
      beta-lactams with a fluoroquinolone or a macrolide is beneficial. In severe
      pneumonia, ureidopenicillins with beta-lactamase inhibitors, broad-spectrum
      cephalosporins, macrolides and fluoroquinolones are used. A combination of a
      broad-spectrum beta-lactam antibacterial (e.g. cefotaxime or ceftriaxone),
      piperacillin/tazobactam and a macrolide is mostly recommended. In patients with a
      predisposition for Pseudomonas aeruginosa, a combination of
      piperacillin/tazobactam, cefepime, imipenem or meropenem and levofloxacin or
      ciprofloxacin is frequently used. Treatment duration of more than 7 days is not
      generally recommended, except for proven infections with P. aeruginosa, for which
      15 days of treatment appears to be appropriate. Further care issues in all
      hospitalized patients are timely administration of antibacterials, oxygen supply
      in case of hypoxaemia, and fluid management and dose adjustments according to
      kidney function. The management of elderly patients with CAP is a challenge.
      Shifts in antimicrobial resistance and the availability of new antibacterials
      will change future clinical practice. Studies investigating new methods to detect
      pathogens, determine the optimal antimicrobial regimen and clarify the duration
      of treatment may assist in further optimizing the management of elderly patients
      with CAP.

PMID- 21721599
TI  - Variation over time in the association between polypharmacy and mortality in the
      older population.
AB  - BACKGROUND: In the older population, multimorbidity is common and 'best practice'
      may invite the prescription of multiple medications. OBJECTIVE: To examine the
      association between polypharmacy, defined as the concurrent use of five or more
      prescription or nonprescription medications, and mortality in 12 423 participants
      aged >=65 years representative of the older population of England and Wales.
      METHODS: Data on self-reported medication use, disability and health conditions
      were collected at baseline in 1991-3. The cohort was followed for up to 18 years
      with full mortality notification. Cox proportional hazards regression adjusted
      for age, baseline institutionalization, smoking, disability and health conditions
      was used to investigate polypharmacy and mortality, stratified by sex. Various
      methods for modelling the time-varying effect of polypharmacy are presented.
      RESULTS: A strong independent association between polypharmacy and mortality
      existed in the short-term (first 2 years) for both men and women. This
      association remained, although attenuated, in the medium-long term (2-18 years of
      follow-up) for women, but became non-significant in the longer term for men.
      CONCLUSIONS: It remains unclear whether polypharmacy is a marker for poor health
      or is an independent risk factor for mortality. However, polypharmacy strongly
      predicts adverse outcomes, and multiple medication use should therefore be
      carefully monitored in the older population.

PMID- 21721600
TI  - Clinical, demographic and functional characteristics associated with
      pharmacotherapy for heart failure in older home care clients: a retrospective,
      population-level, cross-sectional study.
AB  - BACKGROUND: Use of combination pharmacotherapy, including angiotensin-converting
      enzyme (ACE) inhibitors, angiotensin II type 1 receptor antagonists (angiotensin
      receptor blockers) and beta-adrenoceptor antagonists (beta-blockers) in the
      management of heart failure (HF) can reduce mortality, prevent functional decline
      and reduce health service use. However, these first-line therapies are underused
      in older populations. This article describes the use and predictors of use of
      first-line HF therapies in a population-based cohort of older home care clients
      in Ontario, Canada. OBJECTIVES: To examine the use and correlates of first-line
      pharmacotherapy in older home care clients with HF. METHODS: This was a
      retrospective, cross-sectional study of Resident Assessment Instrument - Home
      Care (RAI-HC) data in individuals aged >=65 years receiving home care services in
      the province of Ontario, Canada. Data collected were from all 14 health regions
      in Ontario. Home care clients with HF were identified from among those aged >=65
      years whose first RAI-HC assessment occurred between January 2004 and December
      2007 (n = 176 866). Potential correlates of pharmacotherapy for HF were
      identified from the RAI-HC and examined using multivariable logistic regression.
      RESULTS: HF prevalence was 12.4%. Among clients with HF, 28.6% received no first
      line pharmacotherapy; this proportion declined by 6% over the 4 years studied.
      Only 28.0% were receiving recommended combination therapy. First-line
      pharmacotherapy use was dependent on hypertension and diabetes mellitus status.
      Use of pharmacotherapy was less likely among older clients and those with
      functional impairment, airway disease or behavioural symptoms. CONCLUSIONS:
      Approximately 29% of older home care clients with HF received no first-line HF
      pharmacotherapy, while another 28% received optimal first-line HF
      pharmacotherapy. In addition to the expected clinical correlates, the increased
      likelihood of non-use associated with clients' demographic and functional
      characteristics raises concerns about quality of care. A better understanding of
      how these factors affect prescribing practices, particularly for combination
      therapy, would help to optimize HF disease management. For clinicians, this work
      also serves as a potential reminder to follow guideline recommendations for HF
      management in older, vulnerable adults.

PMID- 21721601
TI  - Co-morbidity and potential treatment conflicts in elderly heart failure patients:
      a retrospective, cross-sectional study of administrative claims data.
AB  - BACKGROUND: Co-morbidity of both cardiac and non-cardiac conditions is common in
      the elderly with heart failure (HF) and can be associated with adverse clinical
      outcomes. OBJECTIVES: The aims of this study were to examine the prevalence of co
      morbidity and potential treatment conflicts that may result in adverse clinical
      outcomes in a large cohort of elderly HF patients. METHODS: We conducted a cross
      sectional study using administrative claims data (1 April to 31 July 2007) from
      the Department of Veterans' Affairs, Australia, on all veterans aged >=65 years
      with HF. Co-morbidities were defined using the pharmaceutical based co-morbidity
      index Rx-Risk-V. Potential treatment conflicts for patients with HF and co-morbid
      diseases were identified from Australian clinical guidelines or reference
      compendia and their prevalence in the data were determined. RESULTS: A total of
      6730 patients were included in the study, with a median of 6 co-morbid conditions
      (interquartile range [IQR] 4-7) and 11 (IQR 8-15) unique medicines. Almost the
      entire HF cohort (97.8%) were identified as having at least one co-morbid
      condition that may cause a potential treatment conflict, with 55% having three or
      more. The conditions identified as being of greatest concern, based on their
      prevalence and potential for treatment conflict, were chronic airways disease,
      depression, chronic pain/inflammatory disease, glaucoma, diabetes mellitus and
      diseases treatable with corticosteroids. CONCLUSIONS: Potential treatment
      conflicts are common in the highly co-morbid population of elderly patients with
      HF, and may influence the therapeutic management of not only HF but all
      conditions present.

PMID- 21721602
TI  - Ketorolac 0.45% ophthalmic solution.
AB  - Ketorolac 0.45% ophthalmic solution is a topical NSAID indicated in the US for
      the treatment of ocular pain and inflammation following cataract surgery. In
      animal studies, the ocular relative bioavailability of single-dose topical
      ketorolac 0.45% ophthalmic solution was 2- to 3-fold higher than that of
      ketorolac 0.4% ophthalmic solution. In two identically designed, randomized,
      double-masked, multicentre trials in adult patients undergoing cataract
      extraction, the proportions of patients with a summed ocular inflammation score
      of zero for anterior chamber cell count plus anterior chamber flare on day 14
      after surgery were significantly greater in those treated with topical ketorolac
      0.45% ophthalmic solution than in those treated with vehicle placebo. Compared
      with placebo, topical ketorolac 0.45% ophthalmic solution significantly increased
      the proportion of patients who were pain-free on the day after surgery in both
      trials. Ketorolac 0.45% ophthalmic solution was generally well tolerated in
      clinical trials with lower overall incidences of treatment-emergent and treatment
      related adverse events than placebo, and with no single treatment-related adverse
      event having a higher incidence than with placebo.

PMID- 21721603
TI  - Communication: Universality of the melting curves for a wide range of interaction
      potentials.
AB  - We demonstrate that the melting curves of various model systems of interacting
      particles collapse to (or are located very close to) a universal master curve on
      a plane of appropriately chosen scaled variables. The physics behind this
      universality is discussed. An equation for the emerging "universal melting curve"
      is proposed. The obtained results can be used to approximately predict melting of
      various substances in a wide range of conditions.

PMID- 21721604
TI  - Communication: A new spectroscopic window on hydroxyl radicals using UV + VUV
      resonant ionization.
AB  - A 1 + 1' multiphoton ionization (MPI) detection scheme for OH radicals is
      presented. The spectroscopic approach combines initial excitation on the well
      characterized A(2)Sigma(+)-X(2)Pi band system with vacuum ultraviolet (VUV)
      ionization via autoionizing Rydberg states that converge on the OH(+) A(3)Pi ion
      state. Jet-cooled MPI spectra on the (1,0) and (2,0) bands show anomalous
      rotational line intensities, while initial excitation on the (0,0) band does not
      lead to detectable OH(+) ions. The onset of ionization with the (1,0) band is
      attributed to an energetic threshold; the combined UV + VUV photon energies are
      above the first member of the autoionizing (A(3)Pi)nd Rydberg series. Comparison
      of the OH 1 + 1' MPI signal with that from single photon VUV ionization of NO
      indicates that the cross section for photoionization from OH A(2)Sigma(+), v' = 1
      is on the order of 10(-17) cm(2).

PMID- 21721605
TI  - Communication: Linear-expansion shooting techniques for accelerating self
      consistent field convergence.
AB  - Based on the corrected Hohenberg-Kohn-Sham total energy density functional [Y. A.
      Zhang and Y. A. Wang, J. Chem. Phys. 130, 144116 (2009)], we have developed two
      linear-expansion shooting techniques (LIST)- direct LIST (LISTd) and indirect
      LIST (LISTi), to accelerate the convergence of self-consistent field (SCF)
      calculations. Case studies show that overall LISTi is the most robust and
      efficient algorithm for accelerating SCF convergence, whereas LISTd is
      advantageous in the early stage of an SCF process. More importantly, LISTi
      outperforms Pulay's direct inversion in the iterative subspace (DIIS) [P. Pulay,
      J. Comput. Chem. 3, 556 (1982)] and its two recent improvements, energy-DIIS [K.
      N. Kudin, G. E. Scuseria, and E. Cances, J. Chem. Phys. 116, 8255 (2002)] and
      augmented Roothaan-Hall energy-DIIS [X. Hu and W. Yang, J. Chem. Phys. 132,
      054109 (2010)].

PMID- 21721606
TI  - A multiconfigurational time-dependent Hartree-Fock method for excited electronic
      states. I. General formalism and application to open-shell states.
AB  - The solution of the time-dependent Schrodinger equation for systems of
      interacting electrons is generally a prohibitive task, for which approximate
      methods are necessary. Popular approaches, such as the time-dependent Hartree
      Fock (TDHF) approximation and time-dependent density functional theory (TDDFT),
      are essentially single-configurational schemes. TDHF is by construction incapable
      of fully accounting for the excited character of the electronic states involved
      in many physical processes of interest; TDDFT, although exact in principle, is
      limited by the currently available exchange-correlation functionals. On the other
      hand, multiconfigurational methods, such as the multiconfigurational time
      dependent Hartree-Fock (MCTDHF) approach, provide an accurate description of the
      excited states and can be systematically improved. However, the computational
      cost becomes prohibitive as the number of degrees of freedom increases, and thus,
      at present, the MCTDHF method is only practical for few-electron systems. In this
      work, we propose an alternative approach which effectively establishes a
      compromise between efficiency and accuracy, by retaining the smallest possible
      number of configurations that catches the essential features of the electronic
      wavefunction. Based on a time-dependent variational principle, we derive the
      MCTDHF working equation for a multiconfigurational expansion with fixed
      coefficients and specialise to the case of general open-shell states, which are
      relevant for many physical processes of interest.

PMID- 21721607
TI  - A multiconfigurational time-dependent Hartree-Fock method for excited electronic
      states. II. Coulomb interaction effects in single conjugated polymer chains.
AB  - Conjugated polymers have attracted considerable attention in the last few decades
      due to their potential for optoelectronic applications. A key step that needs
      optimisation is charge carrier separation following photoexcitation. To
      understand better the dynamics of the exciton prior to charge separation, we have
      performed simulations of the formation and dynamics of localised excitations in
      single conjugated polymer strands. We use a nonadiabatic molecular dynamics
      method which allows for the coupled evolution of the nuclear degrees of freedom
      and of multiconfigurational electronic wavefunctions. We show the relaxation of
      electron-hole pairs to form excitons and oppositely charged polaron pairs and
      discuss the modifications to the relaxation process predicted by the inclusion of
      the Coulomb interaction between the carriers. The issue of charge photogeneration
      in conjugated polymers in dilute solution is also addressed.

PMID- 21721608
TI  - Quantum effects in energy and charge transfer in an artificial photosynthetic
      complex.
AB  - We investigate the quantum dynamics of energy and charge transfer in a wheel
      shaped artificial photosynthetic antenna-reaction center complex. This complex
      consists of six light-harvesting chromophores and an electron-acceptor fullerene.
      To describe quantum effects on a femtosecond time scale, we derive the set of
      exact non-Markovian equations for the Heisenberg operators of this photosynthetic
      complex in contact with a Gaussian heat bath. With these equations we can analyze
      the regime of strong system-bath interactions, where reorganization energies are
      of the order of the intersite exciton couplings. We show that the energy of the
      initially excited antenna chromophores is efficiently funneled to the porphyrin
      fullerene reaction center, where a charge-separated state is set up in a few
      picoseconds, with a quantum yield of the order of 95%. In the single-exciton
      regime, with one antenna chromophore being initially excited, we observe quantum
      beatings of energy between two resonant antenna chromophores with a decoherence
      time of ~100 fs. We also analyze the double-exciton regime, when two porphyrin
      molecules involved in the reaction center are initially excited. In this regime
      we obtain pronounced quantum oscillations of the charge on the fullerene molecule
      with a decoherence time of about 20 fs (at liquid nitrogen temperatures). These
      results show a way to directly detect quantum effects in artificial
      photosynthetic systems.

PMID- 21721609
TI  - A comparison of accelerators for direct energy minimization in electronic
      structure calculations.
AB  - We compare three different methods for direct energy minimization in electronic
      structure calculations where the gradient of the energy functional with respect
      to the molecular orbitals is available. These methods make use of the
      preconditioned gradient to increase robustness. An orbital transformation is used
      to ensure that the orthogonality constraint on the orbitals remains satisfied
      when using standard minimization methods. In addition, we propose an adaptive
      scheme for estimating the curvature of the energy functional to increase the
      performance of a line search free quasi-Newton method. We show that the
      performance of all methods is similar when robustness of the methods is ensured.

PMID- 21721610
TI  - Index k saddles and dividing surfaces in phase space with applications to
      isomerization dynamics.
AB  - In this paper, we continue our studies of the phase space geometry and dynamics
      associated with index k saddles (k > 1) of the potential energy surface. Using
      Poincare-Birkhoff normal form (NF) theory, we give an explicit formula for a
      "dividing surface" in phase space, i.e., a codimension one surface (within the
      energy shell) through which all trajectories that "cross" the region of the index
      k saddle must pass. With a generic non-resonance assumption, the normal form
      provides k (approximate) integrals that describe the saddle dynamics in a
      neighborhood of the index k saddle. These integrals provide a symbolic
      description of all trajectories that pass through a neighborhood of the saddle.
      We give a parametrization of the dividing surface which is used as the basis for
      a numerical method to sample the dividing surface. Our techniques are applied to
      isomerization dynamics on a potential energy surface having four minima; two
      symmetry related pairs of minima are connected by low energy index 1 saddles,
      with the pairs themselves connected via higher energy index 1 saddles and an
      index 2 saddle at the origin. We compute and sample the dividing surface and show
      that our approach enables us to distinguish between concerted crossing ("hilltop
      crossing") isomerizing trajectories and those trajectories that are not concerted
      crossing (potentially sequentially isomerizing trajectories). We then consider
      the effect of additional "bath modes" on the dynamics, by a study of a four
      degree-of-freedom system. For this system we show that the normal form and
      dividing surface can be realized and sampled and that, using the approximate
      integrals of motion and our symbolic description of trajectories, we are able to
      choose initial conditions corresponding to concerted crossing isomerizing
      trajectories and (potentially) sequentially isomerizing trajectories.

PMID- 21721611
TI  - Pade spectrum decompositions of quantum distribution functions and optimal
      hierarchical equations of motion construction for quantum open systems.
AB  - Pade spectrum decomposition is an optimal sum-over-poles expansion scheme of
      Fermi function and Bose function [J. Hu, R. X. Xu, and Y. J. Yan, J. Chem. Phys.
      133, 101106 (2010)]. In this work, we report two additional members to this
      family, from which the best among all sum-over-poles methods could be chosen for
      different cases of application. Methods are developed for determining these three
      Pade spectrum decomposition expansions at machine precision via simple
      algorithms. We exemplify the applications of present development with optimal
      construction of hierarchical equations-of-motion formulations for nonperturbative
      quantum dissipation and quantum transport dynamics. Numerical demonstrations are
      given for two systems. One is the transient transport current to an interacting
      quantum-dots system, together with the involved high-order co-tunneling dynamics.
      Another is the non-Markovian dynamics of a spin-boson system.

PMID- 21721612
TI  - Dynamical reweighting: improved estimates of dynamical properties from
      simulations at multiple temperatures.
AB  - Dynamical averages based on functionals of dynamical trajectories, such as time
      correlation functions, play an important role in determining kinetic or transport
      properties of matter. At temperatures of interest, the expectations of these
      quantities are often dominated by contributions from rare events, making the
      precise calculation of these quantities by molecular dynamics simulation
      difficult. Here, we present a reweighting method for combining simulations from
      multiple temperatures (or from simulated or parallel tempering simulations) to
      compute an optimal estimate of the dynamical properties at the temperature of
      interest without the need to invoke an approximate kinetic model (such as the
      Arrhenius law). Continuous and differentiable estimates of these expectations at
      any temperature in the sampled range can also be computed, along with an
      assessment of the associated statistical uncertainty. For rare events,
      aggregating data from multiple temperatures can produce an estimate with the
      desired precision at greatly reduced computational cost compared with simulations
      conducted at a single temperature. Here, we describe use of the method for the
      canonical (NVT) ensemble using four common models of dynamics (canonical
      distribution of Hamiltonian trajectories, Andersen thermostatting, Langevin, and
      overdamped Langevin or Brownian dynamics), but it can be applied to any
      thermodynamic ensemble provided the ratio of path probabilities at different
      temperatures can be computed. To illustrate the method, we compute a time
      correlation function for solvated terminally-blocked alanine peptide across a
      range of temperatures using trajectories harvested using a modified parallel
      tempering protocol.

PMID- 21721613
TI  - Optimal use of data in parallel tempering simulations for the construction of
      discrete-state Markov models of biomolecular dynamics.
AB  - Parallel tempering (PT) molecular dynamics simulations have been extensively
      investigated as a means of efficient sampling of the configurations of
      biomolecular systems. Recent work has demonstrated how the short physical
      trajectories generated in PT simulations of biomolecules can be used to construct
      the Markov models describing biomolecular dynamics at each simulated temperature.
      While this approach describes the temperature-dependent kinetics, it does not
      make optimal use of all available PT data, instead estimating the rates at a
      given temperature using only data from that temperature. This can be problematic,
      as some relevant transitions or states may not be sufficiently sampled at the
      temperature of interest, but might be readily sampled at nearby temperatures.
      Further, the comparison of temperature-dependent properties can suffer from the
      false assumption that data collected from different temperatures are
      uncorrelated. We propose here a strategy in which, by a simple modification of
      the PT protocol, the harvested trajectories can be reweighted, permitting data
      from all temperatures to contribute to the estimated kinetic model. The method
      reduces the statistical uncertainty in the kinetic model relative to the single
      temperature approach and provides estimates of transition probabilities even for
      transitions not observed at the temperature of interest. Further, the method
      allows the kinetics to be estimated at temperatures other than those at which
      simulations were run. We illustrate this method by applying it to the generation
      of a Markov model of the conformational dynamics of the solvated terminally
      blocked alanine peptide.

PMID- 21721614
TI  - Ab initio study of excited state electronic circular dichroism. Two prototype
      cases: methyl oxirane and R-(+)-1,1'-bi(2-naphthol).
AB  - A computational approach to the calculation of excited state electronic circular
      dichroism (ESECD) spectra of chiral molecules is discussed. Frequency dependent
      quadratic response theory is employed to compute the rotatory strength for
      transitions between excited electronic states, by employing both a magnetic gauge
      dependent and a (velocity-based) magnetic gauge independent approach. Application
      is made to the lowest excited states of two prototypical chiral molecules,
      propylene oxide, also known as 1,2-epoxypropane or methyl oxirane, and R-(+)-1,1'
      bi(2-naphthol), or BINOL. The dependence of the rotatory strength for transitions
      between the lowest three excited states of methyl oxirane upon the quality and
      extension of the basis set is analyzed, by employing a hierarchy of correlation
      consistent basis sets. Once established that basis sets of at least triple zeta
      quality, and at least doubly augmented, are sufficient to ensure sufficiently
      converged results, at least at the Hartree-Fock self-consistent field (HF-SCF)
      level, the rotatory strengths for all transitions between the lowest excited
      electronic states of methyl oxirane are computed and analyzed, employing HF-SCF,
      and density functional theory (DFT) electronic structure models. For DFT, both
      the popular B3LYP and its recently highly successful CAM-B3LYP extension are
      exploited. The strong dependence of the spectra upon electron correlation is
      highlighted. A HF-SCF and DFT study is carried out also for BINOL, a system where
      excited states show the typical pairing structure arising from the interaction of
      the two monomeric moieties, and whose conformational changes following
      photoexcitation were studied recently with via time-resolved CD.

PMID- 21721615
TI  - Benchmark of density functional theory methods on the prediction of bond energies
      and bond distances of noble-gas containing molecules.
AB  - We have tested three pure density functional theory (DFT) functionals, BLYP,
      MPWPW91, MPWB95, and ten hybrid DFT functionals, B3LYP, B3P86, B98, MPW1B95,
      MPW1PW91, BMK, M05-2X, M06-2X, B2GP-PLYP, and DSD-BLYP with a series of commonly
      used basis sets on the performance of predicting the bond energies and bond
      distances of 31 small neutral noble-gas containing molecules. The reference
      structures were obtained using the CCSD(T)/aug-cc-pVTZ theory and the reference
      energies were based on the calculation at the CCSD(T)/CBS level. While in general
      the hybrid functionals performed significantly better than the pure functionals,
      our tests showed a range of performance by these hybrid functionals. For the bond
      energies, the MPW1B95/6-311+G(2df,2pd), BMK/aug-cc-pVTZ, B2GP-PLYP/aug-cc-pVTZ,
      and DSD-BLYP/aug-cc-pVTZ methods stood out with mean unsigned errors of 2.0-2.3
      kcal/mol per molecule. For the bond distances, the MPW1B95/6-311+G(2df,2pd),
      MPW1PW91/6-311+G(2df,2pd), and B3P86/6-311+G(2df,2pd), DSD-BLYP/6-311+G(2df,2pd),
      and DSD-BLYP/aug-cc-pVTZ methods stood out with mean unsigned errors of 0.008
      0.013 A per bond. The current study showed that a careful selection of DFT
      functionals is very important in the study of noble-gas chemistry, and the most
      recommended methods are MPW1B95/6-311+G(2df,2pd) and DSD-BLYP/aug-cc-pVTZ.

PMID- 21721616
TI  - Comparison of two adaptive temperature-based replica exchange methods applied to
      a sharp phase transition of protein unfolding-folding.
AB  - Temperature-based replica exchange (T-ReX) enhances sampling of molecular
      dynamics simulations by autonomously heating and cooling simulation clients via a
      Metropolis exchange criterion. A pathological case for T-ReX can occur when a
      change in state (e.g., folding to unfolding of a protein) has a large energetic
      difference over a short temperature interval leading to insufficient exchanges
      amongst replica clients near the transition temperature. One solution is to allow
      the temperature set to dynamically adapt in the temperature space, thereby
      enriching the population of clients near the transition temperature. In this
      work, we evaluated two approaches for adapting the temperature set: a method that
      equalizes exchange rates over all neighbor temperature pairs and a method that
      attempts to induce clients to visit all temperatures (dubbed "current
      maximization") by positioning many clients at or near the transition temperature.
      As a test case, we simulated the 57-residue SH3 domain of alpha-spectrin.
      Exchange rate equalization yielded the same unfolding-folding transition
      temperature as fixed-temperature ReX with much smoother convergence of this
      value. Surprisingly, the current maximization method yielded a significantly
      lower transition temperature, in close agreement with experimental observation,
      likely due to more extensive sampling of the transition state.

PMID- 21721617
TI  - Analytical evaluation of first-order electrical properties based on the spin-free
      Dirac-Coulomb Hamiltonian.
AB  - We report an analytical scheme for the calculation of first-order electrical
      properties using the spin-free Dirac-Coulomb (SFDC) Hamiltonian, thereby
      exploiting the well-developed density-matrix formulations in nonrelativistic
      coupled-cluster (CC) derivative theory. Orbital relaxation effects are fully
      accounted for by including the relaxation of the correlated orbitals with respect
      to orbitals of all types, viz., frozen-core, occupied, virtual, and negative
      energy state orbitals. To demonstrate the applicability of the presented scheme,
      we report benchmark calculations for first-order electrical properties of the
      hydrogen halides, HX with X = F, Cl, Br, I, At, and a first application to the
      iodo(fluoro)methanes, CH(n)F(3 - n)I, n = 0-3. The results obtained from the SFDC
      calculations are compared to those from nonrelativistic calculations, those
      obtained via leading-order direct perturbation theory as well as those from full
      Dirac-Coulomb calculations. It is shown that the full inclusion of spin-free (SF)
      relativistic effects is necessary to obtain accurate first-order electrical
      properties in the presence of fifth-row elements. The SFDC scheme is also
      recommended for applications to systems containing lighter elements because it
      introduces no extra cost in the rate-determining steps of a CC calculation in
      comparison to the nonrelativistic case. On the other hand, spin-orbit
      contributions are generally small for first-order electrical properties of closed
      shell molecules and may be handled efficiently by means of perturbation theory.

PMID- 21721618
TI  - Brueckner doubles coupled cluster method with the polarizable continuum model of
      solvation.
AB  - We present the theory and implementation for computing the (free) energy and its
      analytical gradients with the Brueckner doubles (BD) coupled cluster method in
      solution, in combination with the polarizable continuum model of solvation (PCM).
      The complete model, called PTED, and an efficient approximation, called PTE, are
      introduced and tested with numerical examples. Implementation details are also
      discussed. A comparison with the coupled-cluster singles and doubles CCSD-PCM
      PTED and CCSD-PCM-PTE schemes, which use Hartree-Fock (HF) orbitals, is
      presented. The results show that the two PTED approaches are mostly equivalent,
      while BD-PCM-PTE is shown to be superior to the corresponding CCSD scheme when
      the HF reference wave function is unstable. The BD-PCM-PTE scheme, whose
      computational cost is equivalent to gas phase BD, is therefore a promising
      approach to study molecular systems with complicated electronic structure in
      solution.

PMID- 21721619
TI  - Decoherence and surface hopping: when can averaging over initial conditions help
      capture the effects of wave packet separation?
AB  - Fewest-switches surface hopping (FSSH) is a popular nonadiabatic dynamics method
      which treats nuclei with classical mechanics and electrons with quantum
      mechanics. In order to simulate the motion of a wave packet as accurately as
      possible, standard FSSH requires a stochastic sampling of the trajectories over a
      distribution of initial conditions corresponding, e.g., to the Wigner
      distribution of the initial quantum wave packet. Although it is well-known that
      FSSH does not properly account for decoherence effects, there is some confusion
      in the literature about whether or not this averaging over a distribution of
      initial conditions can approximate some of the effects of decoherence. In this
      paper, we not only show that averaging over initial conditions does not generally
      account for decoherence, but also why it fails to do so. We also show how an
      apparent improvement in accuracy can be obtained for a fortuitous choice of model
      problems, even though this improvement is not possible, in general. For a basic
      set of one-dimensional and two-dimensional examples, we find significantly
      improved results using our recently introduced augmented FSSH algorithm.

PMID- 21721620
TI  - A general formulation for the efficient evaluation of n-electron integrals over
      products of Gaussian charge distributions with Gaussian geminal functions.
AB  - In this work, we present a general formulation for the evaluation of many
      electron integrals which arise when traditional one particle expansions are
      augmented with explicitly correlated Gaussian geminal functions. The integrand is
      expressed as a product of charge distributions, one for each electron, multiplied
      by one or more Gaussian geminal factors. Our formulation begins by focusing on
      the quadratic form that arises in the general n-electron integral. Using the Rys
      polynomial method for the evaluation of potential energy integrals, we derive a
      general formula for the evaluation of any n-electron integral. This general
      expression contains four parameters omega, theta, v, and h, which can be
      evaluated by an examination of the general quadratic form. Our analysis contains
      general expressions for any n-electron integral over s-type functions as well as
      the recursion needed to build up arbitrary angular momentum. The general
      recursion relation requires at most n + 1 terms for any n-electron integral. To
      illustrate the general method, we develop explicit expressions for the evaluation
      of two, three, and four particle electron repulsion integrals as well as two and
      three particle overlap and nuclear attraction integrals. We conclude our
      exposition with a discussion of a preliminary computational implementation as
      well as general computational requirements. Implementation on parallel computers
      is briefly discussed.

PMID- 21721621
TI  - Mixed quantum-classical simulations of charge transport in organic materials:
      numerical benchmark of the Su-Schrieffer-Heeger model.
AB  - The electron-phonon coupling is critical in determining the intrinsic charge
      carrier and exciton transport properties in organic materials. In this study, we
      consider a Su-Schrieffer-Heeger (SSH) model for molecular crystals, and perform
      numerical benchmark studies for different strategies of simulating the mixed
      quantum-classical dynamics. These methods, which differ in the selection of
      initial conditions and the representation used to solve the time evolution of the
      quantum carriers, are shown to yield similar equilibrium diffusion properties. A
      hybrid approach combining molecular dynamics simulations of nuclear motion and
      quantum-chemical calculations of the electronic Hamiltonian at each geometric
      configuration appears as an attractive strategy to model charge dynamics in large
      size systems "on the fly," yet it relies on the assumption that the quantum
      carriers do not impact the nuclear dynamics. We find that such an approximation
      systematically results in overestimated charge-carrier mobilities, with the
      associated error being negligible when the room-temperature mobility exceeds ~4.8
      cm(2)/Vs (~0.14 cm(2)/Vs) in one-dimensional (two-dimensional) crystals.

PMID- 21721622
TI  - Development and application of the analytical energy gradient for the normalized
      elimination of the small component method.
AB  - The analytical energy gradient of the normalized elimination of the small
      component (NESC) method is derived for the first time and implemented for the
      routine calculation of NESC geometries and other first order molecular
      properties. Essential for the derivation is the correct calculation of the
      transformation matrix U relating the small component to the pseudolarge component
      of the wavefunction. The exact form of ?U/?lambda is derived and its contribution
      to the analytical energy gradient is investigated. The influence of a finite
      nucleus model and that of the picture change is determined. Different ways of
      speeding up the calculation of the NESC gradient are tested. It is shown that
      first order properties can routinely be calculated in combination with Hartree
      Fock, density functional theory (DFT), coupled cluster theory, or any electron
      correlation corrected quantum chemical method, provided the NESC Hamiltonian is
      determined in an efficient, but nevertheless accurate way. The general
      applicability of the analytical NESC gradient is demonstrated by benchmark
      calculations for NESC/CCSD (coupled cluster with all single and double
      excitation) and NESC/DFT involving up to 800 basis functions.

PMID- 21721623
TI  - Optimizing transition interface sampling simulations.
AB  - We demonstrate that a recently proposed adaptive optimization algorithm for
      forward flux sampling simulations [E. E. Borrero and F. A. Escobedo, J. Chem.
      Phys. 129, 024115 (2008)] can be easily applied within the framework of
      transition interface sampling. This optimization algorithm systematically
      identifies the kinetic bottlenecks along the order parameter used to partition
      phase space via interfaces and improves the statistical accuracy of the reaction
      rate constant estimate. In different versions of the algorithm, the number or the
      placement of the interfaces (or both) are varied in order to allocate the
      numerical effort in a balanced way. The algorithm is demonstrated for a simple
      two-dimensional model and for the dipole flip transition of icelike structures
      inside carbon nanotubes. For these test systems, the optimization yielded an
      efficiency increase by a factor of 2-15.

PMID- 21721624
TI  - Photoelectron imaging spectroscopy of nitroethane anions.
AB  - We present low-energy velocity map photoelectron imaging results for bare and Ar
      solvated nitroethane anions. We report an improved value for the adiabatic
      electron affinity of nitroethane of (191 +/- 6) meV which is used to obtain a C
      NO(2) bond dissociation energy of (0.589 +/- 0.019) eV in nitroethane anion. We
      assign a weak feature at (27 +/- 5) meV electron binding energy to the dipole
      bound anion state of nitroethane. Photoelectron angular distributions exhibit
      increasing anisotropy with increasing kinetic energies. The main contributions to
      the photoelectron spectrum of nitroethane anion can be assigned to the
      vibrational modes of the nitro group. Transitions involving torsional motion
      around the CN bond axis lead to strong spectral congestion. Interpretation of the
      photoelectron spectrum is assisted by ab initio calculations and Franck-Condon
      simulations.

PMID- 21721625
TI  - Non-linear dynamics of the photodissociation of nitrous oxide: equilibrium
      points, periodic orbits, and transition states.
AB  - The diffuse vibrational bands, observed in the ultraviolet photodissociation
      spectrum of nitrous oxide by exciting the molecule in the first (1)A' state, have
      recently been attributed to resonances localized mainly in the NN stretch and
      bend degrees of freedom. To further investigate the origin of this localization,
      fundamental families of periodic orbits emanating from several stationary points
      of the (1)A' potential energy surface and bifurcations of them are computed. We
      demonstrate that center-saddle bifurcations of periodic orbits are the main
      mechanism for creating stable regions in phase space that can support the partial
      trapping of the wave packet, and thus they explain the observed spectra. A non
      linear mechanical methodology, which involves the calculation of equilibria,
      periodic orbits, and transition states in normal form coordinates, is applied for
      an in detail exploration of phase space. The fingerprints of the phase space
      structures in the quantum world are identified by solving the time dependent
      Schrodinger equation and calculating autocorrelation functions. This demonstrates
      that different reaction channels could be controlled if exact knowledge of the
      phase space structure is available to guide the initial excitation of the
      molecule.

PMID- 21721626
TI  - Gas phase solvatochromic effects of phenol and naphthol photoacids.
AB  - A quantum chemical study of spectral shifts by single molecule solvation of
      phenol, alpha-naphthol, and beta-naphthol is presented. The methods employed
      include the equation-of-motion coupled cluster, the similarity transformed
      equation-of-motion coupled cluster, single excitation configuration-interaction,
      and time-dependent density functional theory. Based on the calculations, there is
      no evidence that there is significant charge-transfer between the solute and the
      solvent. Instead, it appears that the observed solvation redshift is due to the
      nature of the excited state on the solute molecule.

PMID- 21721627
TI  - Sulfur 1s near-edge x-ray absorption fine structure (NEXAFS) of thiol and
      thioether compounds.
AB  - The speciation and quantification of sulfur species based on sulfur K-edge x-ray
      absorption spectroscopy is of wide interest, particularly for biological and
      petroleum science. These tasks require a firm understanding of the sulfur 1s near
      edge x-ray absorption fine structure (NEXAFS) spectra of relevant species. To
      this end, we have examined the gas phase sulfur 1s NEXAFS spectra of a group of
      simple thiol and thioether compounds. These high-resolution gas phase spectra are
      free of solid-state broadening, charging, and saturation effects common in the
      NEXAFS spectra of solids. These experimental data have been further analyzed with
      the aid of improved virtual orbital Hartree-Fock ab initio calculations. The
      experimental sulfur 1s NEXAFS spectra show fine features predicted by
      calculation, and the combination of experiment and calculation has been used to
      improve assignment of spectroscopic features relevant for the speciation and
      quantification of the sulfur compounds.

PMID- 21721628
TI  - The oxidation of Al atoms embedded in water clusters: a dynamical study of the
      relay (Grotthuss-like) mechanism.
AB  - The dynamics of the oxidation of micro-hydrated Al atoms has been studied taking
      into account the effect of tunneling. Neutral aggregates of the type
      Al.(H(2)O)(n), n = {1-8} and Al.(H(2)O)(n).m(H(2)O) have been considered, where
      Al.(H(2)O)(n) has been treated by density functional theory (DFT) theory and the
      other m = {52, 56} waters have been represented by an effective fragment
      potential (EFP). The results indicate that oxidation may take place quite fast by
      a relay-type mechanism occurring within a ring of water molecules which involves
      the Al atom, in which a H atom is transferred. The inclusion of water molecules
      to form the ring from n = 1 to n = 3 tends to reduce the barrier height but
      results in lower tunneling transmission factors. The "optimal" ring is the one
      containing three waters; the four-water one produces lower rates. Coordination of
      additional waters to Al forming a second ring does not appear to have a further
      catalytic effect. The inclusion of many additional waters as EFPs, to simulate
      larger aggregates, increases the rates significantly. The extrapolation to bulk
      conditions and the possible impact of ionic mechanisms have also been discussed.

PMID- 21721629
TI  - Ultrafast internal conversion in ethylene. I. The excited state lifetime.
AB  - Using a combined theoretical and experimental approach, we investigate the non
      adiabatic dynamics of the prototypical ethylene (C(2)H(4)) molecule upon pi ->
      pi* excitation. In this first part of a two part series, we focus on the lifetime
      of the excited electronic state. The femtosecond time-resolved photoelectron
      spectrum (TRPES) of ethylene is simulated based on our recent molecular dynamics
      simulation using the ab initio multiple spawning method with multi-state second
      order perturbation theory [H. Tao, B. G. Levine, and T. J. Martinez, J. Phys.
      Chem. A 113, 13656 (2009)]. We find excellent agreement between the TRPES
      calculation and the photoion signal observed in a pump-probe experiment using
      femtosecond vacuum ultraviolet (hnu = 7.7 eV) pulses for both pump and probe.
      These results explain the apparent discrepancy over the excited state lifetime
      between theory and experiment that has existed for ten years, with experiments
      [e.g., P. Farmanara, V. Stert, and W. Radloff, Chem. Phys. Lett. 288, 518 (1998)
      and K. Kosma, S. A. Trushin, W. Fuss, and W. E. Schmid, J. Phys. Chem. A 112,
      7514 (2008)] reporting much shorter lifetimes than predicted by theory.
      Investigation of the TRPES indicates that the fast decay of the photoion yield
      originates from both energetic and electronic factors, with the energetic factor
      playing a larger role in shaping the signal.

PMID- 21721630
TI  - A new "spectroscopic" potential energy surface for formaldehyde in its ground
      electronic state.
AB  - We report a new "spectroscopic" potential energy surface (PES) of formaldehyde
      (H(2)(12)C(16)O) in its ground electronic state, obtained by refining an ab
      initio PES in a least-squares fitting to the experimental spectroscopic data for
      formaldehyde currently available in the literature. The ab initio PES was
      computed using the CCSD(T)/aug-cc-pVQZ method at 30 840 geometries that cover the
      energy range up to 44 000 cm(-1) above equilibrium. Ro-vibrational energies of
      formaldehyde were determined variationally for this ab initio PES by means of the
      program TROVE [Theoretical ROtation-Vibration Energies; S. N. Yurchenko, W.
      Thiel, and P. Jensen, J. Mol. Spectrosc. 245, 126 (2007)]. The parameter values
      in the analytical representation of the PES were optimized in fittings to 319 ro
      vibrational energies with J = 0, 1, 2, and 5. The initial parameter values in the
      fittings were those of the ab initio PES, the ro-vibrational eigenfunctions
      obtained from this PES served as a basis set during the fitting process, and
      constraints were imposed to ensure that the refined PES does not deviate
      unphysically from the ab initio one in regions of configuration space not sampled
      by the experimental data. The resulting refined PES, referred to as H(2)CO-2011,
      reproduces the available experimental J <= 5 data with a root-mean-square error
      of 0.04 cm(-1).

PMID- 21721631
TI  - Axis-switching in the vibrationless A<-X transition of the jet-cooled deuterated
      methyl peroxy radical CD3O2.
AB  - The jet-cooled high resolution spectrum of the vibrationless A<-X transition of
      the deuterated species of the methyl peroxy radical has been recently published
      in this journal (S. Wu, P. Dupre, P. Rupper, and T. A. Miller, J. Chem. Phys.
      127, 224305 (2007)). The spectrum was analyzed using a rigid-rotor model with
      quadratic spin-rotation coupling. The analysis was based on the fit of ~350
      partially resolved line positions and was quite satisfactory. However, the full
      simulation of the spectral intensity clearly identifies a lack of ability to
      reproduce relatively small line clumps ("extra" lines) located between the two
      main central Q branches. This is indicating of an incomplete initial analysis. In
      the present paper we reanalyze this electronic transition by considering a
      reference-frame axis-switching resulting from the nuclear rearrangement
      associated to the electronic transition (spectra obtained at two different
      temperatures are considered). The potential energy hypersurfaces of the two
      electronic states are sufficiently dissimilar to induce changes in the molecule
      geometry, particularly, the angle COO, which induces a rotation (~1.7 degrees )
      of the principal axes of inertia located in the molecule symmetry plane. The
      present analysis is supported by a global fitting of the spectrum intensity and
      gives rise to a slightly different set of molecular constants. Attention is paid
      to the wavefunction symmetry assignment of a non-orthorhombic molecule. Couplings
      due to the torsion of the methyl group are discussed in the following paper (P.
      Dupre, J. Chem. Phys. 134, 244309 (2011)).

PMID- 21721632
TI  - Internal rotation: single diagonalization approach versus standard approaches,
      application to the methyl peroxy radical A<-X transition.
AB  - A new approach avoiding double (two-step) diagonalization is proposed to deal
      with internal rotation. The development of this method was stimulated by the jet
      cooled high resolution spectrum of the vibrationless A<-X transition of the
      deuterated species of the methyl peroxy radical. This spectrum, originally
      analyzed with a rigid rotor Hamiltonian including spin-rotation but neglecting
      internal rotation, has been revisited in the previous paper (P. Dupre, J. Chem.
      Phys. 134, 244308 (2011)) and a determinable yaw of the molecular principal axes
      of inertia about the c-axis (axis-switching) during the electronic transition was
      established. The spectral resolution of the jet-cooled data of the vibrationless
      transition (~7355 - 7390 cm(-1)) does not allow the observation of splitting due
      to internal rotation of the methyl top, but when these data are combined with the
      low resolution room temperature data (~7200 - 8000 cm(-1)) accurate fits or
      simulations of the two sets of data are possible. A recent study of the room
      temperature data has been reported in this journal (G. M. P. Just et al., J.
      Chem. Phys. 127, 044310 (2007)) showing evidence of the internal rotation
      coupling by analyzing the intensity of the torsional mode energy progression.
      That investigation combined ab initio quantum chemistry calculations and the rho
      axis-method (RAM) to model the internal rotation. Here, a comparison of full
      spectral intensity analyses based on both the usual RAM and on the new approach
      requiring a single-diagonalization principal-axis-method is presented. The
      comparison favors the single-diagonalization approach. Axis-switching and spin
      rotation coupling are incorporated in the analysis, in which the use of the
      principal axes of inertia is maintained. Symmetries, energy levels, and
      advantages are carefully discussed for all methods.

PMID- 21721633
TI  - Cis-trans isomerization in the S1 state of acetylene: identification of cis-well
      vibrational levels.
AB  - A systematic analysis of the S(1)-trans (A(1)A(u)) state of acetylene, using IR
      UV double resonance along with one-photon fluorescence excitation spectra, has
      allowed assignment of at least part of every single vibrational state or polyad
      up to a vibrational energy of 4200 cm(-1). Four observed vibrational levels
      remain unassigned, for which no place can be found in the level structure of the
      trans-well. The most prominent of these lies at 46 175 cm(-1). Its (13)C isotope
      shift, exceptionally long radiative lifetime, unexpected rotational selection
      rules, and lack of significant Zeeman effect, combined with the fact that no
      other singlet electronic states are expected at this energy, indicate that it is
      a vibrational level of the S(1)-cis isomer (A(1)A(2)). Guided by ab initio
      calculations [J. H. Baraban, A. R. Beck, A. H. Steeves, J. F. Stanton, and R. W.
      Field, J. Chem. Phys. 134, 244311 (2011)] of the cis-well vibrational
      frequencies, the vibrational assignments of these four levels can be established
      from their vibrational symmetries together with the (13)C isotope shift of the 46
      175 cm(-1) level (assigned here as cis-3(1)6(1)). The S(1)-cis zero-point level
      is deduced to lie near 44 900 cm(-1), and the nu(6) vibrational frequency of the
      S(1)-cis well is found to be roughly 565 cm(-1); these values are in remarkably
      good agreement with the results of recent ab initio calculations. The 46 175 cm(
      1) vibrational level is found to have a 3.9 cm(-1) staggering of its K-rotational
      structure as a result of quantum mechanical tunneling through the isomerization
      barrier. Such tunneling does not give rise to ammonia-type inversion doubling,
      because the cis and trans isomers are not equivalent; instead the odd-K
      rotational levels of a given vibrational level are systematically shifted
      relative to the even-K rotational levels, leading to a staggering of the K
      structure. These various observations represent the first definite assignment of
      an isomer of acetylene that was previously thought to be unobservable, as well as
      the first high resolution spectroscopic results describing cis-trans
      isomerization.

PMID- 21721634
TI  - Reduced dimension discrete variable representation study of cis-trans
      isomerization in the S1 state of C2H2.
AB  - Isomerization between the cis and trans conformers of the S(1) state of acetylene
      is studied using a reduced dimension discrete variable representation (DVR)
      calculation. Existing DVR techniques are combined with a high accuracy potential
      energy surface and a kinetic energy operator derived from FG theory to yield an
      effective but simple Hamiltonian for treating large amplitude motions. The
      spectroscopic signatures of the S(1) isomerization are discussed, with emphasis
      on the vibrational aspects. The presence of a low barrier to isomerization causes
      distortion of the trans vibrational level structure and the appearance of
      nominally electronically forbidden A (1)A(2)<-X (1)Sigma(g)(+) transitions to
      vibrational levels of the cis conformer. Both of these effects are modeled in
      agreement with experimental results, and the underlying mechanisms of tunneling
      and state mixing are elucidated by use of the calculated vibrational
      wavefunctions.

PMID- 21721635
TI  - Threshold photoelectron study of naphthalene, anthracene, pyrene, 1,2
      dihydronaphthalene, and 9,10-dihydroanthracene.
AB  - Threshold photoelectron spectra (TPESs) were obtained for naphthalene,
      anthracene, pyrene, 1,2-dihydronaphthalene, and 9,10-dihydroanthracene using
      imaging photoelectron photoion coincidence spectroscopy, from threshold to a
      photon energy of ~20 eV. Outer valence Green's function calculations at the
      OVGF/cc-pVTZ level of theory were used to assign molecular orbitals to the
      observed TPES features. There is generally good agreement between the predicted
      and observed bands. Threshold regions for each molecule exhibit vibrational
      structure which is readily assigned based on previous PES studies. While the
      measured adiabatic ionization energies (IE(a)) for naphthalene, anthracene, and
      pyrene are in good agreement with previous works, new values are reported for the
      two dihydro species (1,2-dihydronaphthalene, 8.010 +/- 0.010 eV and 9,10
      dihydroanthracene, 8.335 +/- 0.010 eV). A comparison is also made with the
      G3//B3LYP composite method, which consistently overestimates the IE values by
      0.06-0.09 eV. The double ionization energies for anthracene and pyrene have been
      measured to be 19.3 +/- 0.2 and 19.8 +/- 0.2 eV, respectively.

PMID- 21721636
TI  - Infrared spectra and quantum chemical calculations of the uranium-carbon
      molecules UC, CUC, UCH, and U(CC)2.
AB  - Laser evaporation of carbon rich uranium/carbon alloy targets into condensing
      argon or neon matrix samples gives weak infrared absorptions that increase on
      annealing, which can be assigned to new uranium carbon bearing species. New bands
      at 827.6 cm(-1) in solid argon or 871.7 cm(-1) in neon become doublets with mixed
      carbon 12 and 13 isotopes and exhibit the 1.0381 carbon isotopic frequency ratio
      for the UC diatomic molecule. Another new band at 891.4 cm(-1) in argon gives a
      three-band mixed isotopic spectrum with the 1.0366 carbon isotopic frequency
      ratio, which is characteristic of the anti-symmetric stretching vibration of a
      linear CUC molecule. No evidence was found for the lower energy cyclic U(CC)
      isomer. Other bands at 798.6 and 544.0 cm(-1) are identified as UCH, which has a
      uranium-carbon triple bond similar to that in UC. Evidence is found for bicyclic
      U(CC)(2) and tricyclic U(CC)(3). This work shows that U and C atoms react
      spontaneously to form the uranium carbide U=C and C=U=C molecules with uranium
      carbon triple bonds.

PMID- 21721637
TI  - Confined water inside single-walled carbon nanotubes: global phase diagram and
      effect of finite length.
AB  - Studies on confined water are important not only from the viewpoint of scientific
      interest but also for the development of new nanoscale devices. In this work, we
      aimed to clarify the properties of confined water in the cylindrical pores of
      single-walled carbon nanotubes (SWCNTs) that had diameters in the range of 1.46
      to 2.40 nm. A combination of x-ray diffraction (XRD), nuclear magnetic resonance,
      and electrical resistance measurements revealed that water inside SWCNTs with
      diameters between 1.68 and 2.40 nm undergoes a wet-dry type transition with the
      lowering of temperature; below the transition temperature T(wd), water was
      ejected from the SWCNTs. T(wd) increased with increasing SWCNT diameter D. For
      the SWCNTs with D = 1.68, 2.00, 2.18, and 2.40 nm, T(wd) obtained by the XRD
      measurements were 218, 225, 236, and 237 K, respectively. We performed a
      systematic study on finite length SWCNT systems using classical molecular
      dynamics calculations to clarify the effect of open ends of the SWCNTs and water
      content on the water structure. It was found that ice structures that were formed
      at low temperatures were strongly affected by the bore diameter, a = D -
      sigma(OC), where sigma(OC) is gap distance between the SWCNT and oxygen atom in
      water, and the number of water molecules in the system. In small pores (a < 1.02
      nm), tubule ices or the so-called ice nanotubes (ice NTs) were formed
      irrespective of the water content. On the other hand, in larger pores (a > 1.10
      nm) with small water content, filled water clusters were formed leaving some
      empty space in the SWCNT pore, which grew to fill the pore with increasing water
      content. For pores with sizes in between these two regimes (1.02 < a < 1.10 nm),
      tubule ice also appeared with small water content and grew with increasing water
      content. However, once the tubule ice filled the entire SWCNT pore, further
      increase in the water content resulted in encapsulation of the additional water
      molecules inside the tubule ice. Corresponding XRD measurements on SWCNTs with a
      mean diameter of 1.46 nm strongly suggested the presence of such a filled
      structure.

PMID- 21721638
TI  - Terahertz spectrum and normal-mode relaxation in pentaerythritol tetranitrate:
      effect of changes in bond-stretching force-field terms.
AB  - Terahertz (THz) active normal-mode relaxation in crystalline pentaerythritol
      tetranitrate (PETN) was studied using classical molecular dynamics simulations
      for energy and density conditions corresponding to room temperature and
      atmospheric pressure. Two modifications to the fully flexible non-reactive force
      field due to Borodin et al. [J. Phys. Chem. B 112, 734 (2008)] used in a previous
      study of THz-active normal-mode relaxation in PETN [J. Chem. Phys. 134, 014513
      (2011)] were considered to assess the sensitivity of the earlier predictions to
      details of the covalent bond-stretching terms in the force field. In the first
      modification the harmonic bond-stretching potential was replaced with the Morse
      potential to study the effect of bond anharmonicity on the THz-region mode
      relaxation. In the second modification the C-H and nitro-group N-O bond lengths
      were constrained to constant values to mimic lower quantum occupation numbers for
      those high-frequency modes. The results for relaxation times of the initially
      excited modes were found to be insensitive to either force-field modification.
      Overall time scales for energy transfer to other modes in the system were
      essentially unaffected by the force-field modifications, whereas the detailed
      pathways by which the energy transfer occurs are more complicated for the Morse
      potential than for the harmonic-bond and fixed-bond cases. Terahertz infrared
      absorption spectra constructed using calculated normal-mode frequencies,
      transition dipoles, and relaxation times for THz-active modes were compared to
      the spectra obtained from the Fourier transform of the dipole-dipole time
      autocorrelation function (DDACF). Results from the two approaches are in near
      agreement with each other and with experimental results in terms of main peak
      positions. Both theoretical methods yield narrower peaks than observed
      experimentally and in addition predict a weaker peak at omega ~ 50 cm(-1) that is
      weak or absent experimentally. Peaks obtained using the DDACF approach are
      broader than those obtained from the normal-mode relaxation method.

PMID- 21721639
TI  - Vibrationally quantum-state-specific dynamics of the reactions of CN radicals
      with organic molecules in solution.
AB  - The dynamics of reactions of CN radicals with cyclohexane, d(12)-cyclohexane, and
      tetramethylsilane have been studied in solutions of chloroform, dichloromethane,
      and the deuterated variants of these solvents using ultraviolet photolysis of ICN
      to initiate a reaction. The H(D)-atom abstraction reactions produce HCN (DCN)
      that is probed in absorption with sub-picosecond time resolution using ~500 cm(
      1) bandwidth infrared (IR) pulses in the spectral regions corresponding to C-H
      (or C-D) and C=N stretching mode fundamental and hot bands. Equivalent IR spectra
      were obtained for the reactions of CN radicals with the pure solvents. In all
      cases, the reaction products are formed at early times with a strong propensity
      for vibrational excitation of the C-H (or C-D) stretching (v(3)) and H-C-N (D-C
      N) bending (v(2)) modes, and for DCN products there is also evidence of
      vibrational excitation of the v(1) mode, which involves stretching of the C=N
      bond. The vibrationally excited products relax to the ground vibrational level of
      HCN (DCN) with time constants of ~130-270 ps (depending on molecule and solvent),
      and the majority of the HCN (DCN) in this ground level is formed by vibrational
      relaxation, instead of directly from the chemical reaction. The time-dependence
      of reactive production of HCN (DCN) and vibrational relaxation is analysed using
      a vibrationally quantum-state specific kinetic model. The experimental outcomes
      are indicative of dynamics of exothermic reactions over an energy surface with an
      early transition state. Although the presence of the chlorinated solvent may
      reduce the extent of vibrational excitation of the nascent products, the early
      time chemical reaction dynamics in these liquid solvents are deduced to be very
      similar to those for isolated collisions in the gas phase. The transient IR
      spectra show additional spectroscopic absorption features centered at 2037 cm(-1)
      and 2065 cm(-1) (in CHCl(3)) that are assigned, respectively, to CN-solvent
      complexes and recombination of I atoms with CN radicals to form INC molecules.
      These products build up rapidly, with respective time constants of 8-26 and 11-22
      ps. A further, slower rise in the INC absorption signal (with time constant >500
      ps) is attributed to diffusive recombination after escape from the initial
      solvent cage and accounts for more than 2/3 of the observed INC.

PMID- 21721640
TI  - Coinage metal (4, 4) nanotubes, simulated by first-principles calculations.
AB  - The structural stability of coinage metal nanotubes with a square cross-section
      has been investigated by the first-principles numerical simulations. In addition
      to the reported (4, 4) silver tube, it is found that the hollow (4, 4) copper and
      gold nanotubes can also be formed by applying an appropriate stress to an
      8(A)/8(B) fcc wire. The stability of these coinage metal (4, 4) nanotubes, formed
      by tip-stretching the wires, has been explained by a local minimum in the string
      tension variation with their tube lengths. Interestingly, we have explained why a
      low-stress stretching is needed to obtain the (4, 4) Cu tube in contrast to a
      higher one for both the (4, 4) Ag and Au tubes due to the larger stiffness
      coefficient of copper than those of silver and gold, which could be proved by
      future experiments.

PMID- 21721641
TI  - Computer investigations on the asymptotic behavior of the rate coefficient for
      the annihilation reaction A + A -> product and the trapping reaction in three
      dimensions.
AB  - We have performed intensive computer simulations of the irreversible annihilation
      reaction: A + A -> C + C and of the trapping reaction: A + B -> C + B for a
      variety of three-dimensional fluids composed of identical spherical particles. We
      have found a significant difference in the asymptotic behavior of the rate
      coefficients for these reactions. Both the rate coefficients converge to the same
      value with time t going to infinity but the convergence rate is different: the
      O(t(-1/2)) term for the annihilation reaction is higher than the corresponding
      term for the trapping reaction. The simulation results suggest that ratio of the
      terms is a universal quantity with the value equal to 2 or slightly above. A
      model for the annihilation reaction based on the superposition approximation
      predicts the difference in the O(t(-1/2)) terms, but overestimates the value for
      the annihilation reaction by about 30%. We have also performed simulations for
      the dimerization process: A + A -> E, where E stands for a dimer. The
      dimerization decreases the reaction rate due to the decrease in the diffusion
      constant for A. The effect is successfully predicted by a simple model.

PMID- 21721642
TI  - Brownian dynamics simulation of a model simple electrolyte in solvents of low
      dielectric constant.
AB  - Brownian dynamics simulations are performed to investigate the ionic transport of
      model simple electrolytes, in which ions are interacting with each other through
      the repulsive core and Coulombic interactions. The equivalent conductivity and
      self-diffusion coefficient show minima as the function of the number density of
      ions when the dielectric constant of the solvent is low. Although the minimum of
      the former is in harmony with various experiments, no experiment has ever been
      reported on that of the latter. The analysis of time-dependent transport
      coefficients reveals that the presence of the minima is ascribed to the slow
      dynamics, rather than to static association models. The inclusion of a model
      function that resembles the short-range part of the potential of mean force
      induced by solvent affects the transport coefficients qualitatively, which
      suggests the importance of solvent-induced potential of mean force in the
      conduction mechanism of electrolytes in solvents of low dielectric constant.

PMID- 21721643
TI  - Intermolecular vibrations and fast relaxations in supercooled ionic liquids.
AB  - Short-time dynamics of ionic liquids has been investigated by low-frequency Raman
      spectroscopy (4 < omega < 100 cm(-1)) within the supercooled liquid range. Raman
      spectra are reported for ionic liquids with the same anion,
      bis(trifluoromethylsulfonyl)imide, and different cations: 1-butyl-3
      methylimidazolium, 1-hexyl-3-methylimidazolium, 1-butyl-1-methylpiperidinium,
      trimethylbutylammonium, and tributylmethylammonium. It is shown that low
      frequency Raman spectroscopy provides similar results as optical Kerr effect
      (OKE) spectroscopy, which has been used to study intermolecular vibrations in
      ionic liquids. The comparison of ionic liquids containing aromatic and non
      aromatic cations identifies the characteristic feature in Raman spectra usually
      assigned to librational motion of the imidazolium ring. The strength of the fast
      relaxations (quasi-elastic scattering, QES) and the intermolecular vibrational
      contribution (boson peak) of ionic liquids with non-aromatic cations are
      significantly lower than imidazolium ionic liquids. A correlation length assigned
      to the boson peak vibrations was estimated from the frequency of the maximum of
      the boson peak and experimental data of sound velocity. The correlation length
      related to the boson peak (~19 A) does not change with the length of the alkyl
      chain in imidazolium cations, in contrast to the position of the first-sharp
      diffraction peak observed in neutron and X-ray scattering measurements of ionic
      liquids. The rate of change of the QES intensity in the supercooled liquid range
      is compared with data of excess entropy, free volume, and mean-squared
      displacement recently reported for ionic liquids. The temperature dependence of
      the QES intensity in ionic liquids illustrates relationships between short-time
      dynamics and long-time structural relaxation that have been proposed for glass
      forming liquids.

PMID- 21721644
TI  - The oxidation of tyrosine and tryptophan studied by a molecular dynamics normal
      hydrogen electrode.
AB  - The thermochemical constants for the oxidation of tyrosine and tryptophan through
      proton coupled electron transfer in aqueous solution have been computed applying
      a recently developed density functional theory (DFT) based molecular dynamics
      method for reversible elimination of protons and electrons. This method enables
      us to estimate the solvation free energy of a proton (H(+)) in a periodic model
      system from the free energy for the deprotonation of an aqueous hydronium ion
      (H(3)O(+)). Using the computed solvation free energy of H(+) as reference, the
      deprotonation and oxidation free energies of an aqueous species can be converted
      to pK(a) and normal hydrogen electrode (NHE) potentials. This conversion requires
      certain thermochemical corrections which were first presented in a similar study
      of the oxidation of hydrobenzoquinone [J. Cheng, M. Sulpizi, and M. Sprik, J.
      Chem. Phys. 131, 154504 (2009)]. Taking a different view of the thermodynamic
      status of the hydronium ion, these thermochemical corrections are revised in the
      present work. The key difference with the previous scheme is that the hydronium
      is now treated as an intermediate in the transfer of the proton from solution to
      the gas-phase. The accuracy of the method is assessed by a detailed comparison of
      the computed pK(a), NHE potentials and dehydrogenation free energies to
      experiment. As a further application of the technique, we have analyzed the role
      of the solvent in the oxidation of tyrosine by the tryptophan radical. The free
      energy change computed for this hydrogen atom transfer reaction is very similar
      to the gas-phase value, in agreement with experiment. The molecular dynamics
      results however, show that the minimal solvent effect on the reaction free energy
      is accompanied by a significant reorganization of the solvent.

PMID- 21721645
TI  - On the behavior of Bronsted-Evans-Polanyi relations for transition metal oxides.
AB  - Versatile Bronsted-Evans-Polanyi (BEP) relations are found from density
      functional theory for a wide range of transition metal oxides including rutiles
      and perovskites. For oxides, the relation depends on the type of oxide, the
      active site, and the dissociating molecule. The slope of the BEP relation is
      strongly coupled to the adsorbate geometry in the transition state. If it is
      final state-like the dissociative chemisorption energy can be considered as a
      descriptor for the dissociation. If it is initial state-like, on the other hand,
      the dissociative chemisorption energy is not suitable as descriptor for the
      dissociation. Dissociation of molecules with strong intramolecular bonds belong
      to the former and molecules with weak intramolecular bonds to the latter group.
      We show, for the prototype system La-perovskites, that there is a "cyclic"
      behavior in the transition state characteristics upon change of the active
      transition metal of the oxide.

PMID- 21721646
TI  - Anomalies in supercooled NaCl aqueous solutions: a microscopic perspective.
AB  - In this work we studied the effect of NaCl on the thermodynamic and dynamic
      properties of supercooled water, for salt concentrations between 0.19 and 1.33
      mol kg(-1), using molecular dynamic simulations for TIP5P/E water model and ion
      parameters specially designed to be used in combination with this potential. We
      studied the isobaric heat capacity (C(p)) temperature dependence and observed a
      maximum in C(p), occurring at T(m), that moves to lower temperature values with
      increasing salt concentration. Many characteristic changes were observed at
      scaled temperature T/T(m) ~ 0.96, namely a minimum in the density of the system,
      a reduction of the slope of the number of hydrogen bonds vs. temperature, and a
      crossover from Vogel-Tamman-Fulcher to Arrhenius dynamics. Finally, at low
      temperatures we observed that water dynamics become heterogeneous with an
      apparently common relationship between the fraction of immobile molecules and
      T/T(m) for all studied systems.

PMID- 21721647
TI  - Polarized Raman spectroscopic study on the solvent state of glassy LiCl aqueous
      solutions and the state of relaxed high-density amorphous ices.
AB  - We measure polarized OH-stretching Raman spectra of the glassy lithium chloride
      aqueous solutions (LiClaq solutions) and the relaxed high-density amorphous ices
      (HDA). The totally OH symmetric vibrational mode around 3100 cm(-1) (g(1) mode)
      for the glassy LiClaq solutions of 14.3 mol% and the g(1) mode for the glassy
      LiClaq solution of 10.0 mol% seem to be similar to the g(1) mode for HDA at high
      pressure and the g(1) mode for HDA at 1 atm, respectively. This indicates that
      the solvent state of glassy LiClaq solution relates to the state of HDA and that
      the attenuation of the salt effect on water is equivalent to the attenuation of
      the pressure effect on water. This suggests a possibility that the hydration in
      electrolyte aqueous solution may relate to high-density liquid water.

PMID- 21721648
TI  - Kinetic enhancement in nanoscale electrochemical systems caused by non-normal
      distributions of the electrode potential.
AB  - We have recently shown [Proc. Natl. Acad. Sci. U.S.A. 107, 4528 (2010)] that the
      discreteness and stochasticity of an electron transfer event on a resistively
      coupled nanoelectrode causes mesoscopic fluctuations in time of the electrode
      potential. These fluctuations give rise to a time-average faradaic current
      density substantially larger than in the macroscopic limit. The deviations result
      to a large extent from the potentiostatic control, which imposes a constraint on
      the evolution of the electrode potential that leads to non-normal distributions.
      The degree of freedom of the electrode potential requires a resistance between
      nanoelectrode and metallic support. In this article, we study the dependence of
      the mesoscopic stochastic dynamics on this resistance (assumed to be ohmic). We
      show that the enhancement of the reaction rate vanishes in both limits, zero and
      infinite resistance. The distribution of the electrode potential continuously
      transforms from a normal distribution at infinite resistance (the galvanostatic
      limit), through a more and more peaked distribution with increasingly important
      rare events to the deterministic behavior at zero resistance.

PMID- 21721649
TI  - Effect of nanotube-length on the transport properties of single-file water
      molecules: transition from bidirectional to unidirectional.
AB  - We use molecular dynamics (MD) simulations to study the transport of single-file
      water molecules through carbon nanotubes (CNTs) with various lengths in an
      electric field. Most importantly, we find that even the water dipoles inside the
      CNT are maintained along the field direction, a large amount of water molecules
      can still transport against the field direction for short CNTs, leading to a low
      unidirectional transport efficiency (eta). As the CNT length increases, the
      efficiency eta will increase remarkably, and achieves the maximum value of 1.0 at
      or exceeding a critical CNT length. Consequently, the transition from
      bidirectional to unidirectional transport is observed and is found to be relevant
      to thermal fluctuations of the two reservoirs, which is explored by the
      interaction between water molecules inside and outside the CNT. We also find that
      the water flow vs CNT length follows an exponential decay of f  ~  exp (-
      L/L(0)), and the average translocation time of individual water molecules yields
      to a power law of tau(trans)  ~  L(upsilon), where L(0) and nu are constant and
      slightly depend on the field strength. We further compare our results with the
      continuous-time random-walk (CTRW) model and find that the water flow can also be
      described by a power law of f  ~  L(-MU) modified from CTRW. Our results provide
      some new physical insights into the biased transport of single-file water
      molecules, which show the feasibility of using CNTs with any length to pump water
      in an electric field. The mechanism is important for designing efficient
      nanofluidic apparatuses.

PMID- 21721650
TI  - Ultrasoft primitive model of polyionic solutions: structure, aggregation, and
      dynamics.
AB  - We introduce an ultrasoft core model of interpenetrating polycations and
      polyanions, with continuous Gaussian charge distributions, to investigate
      polyelectrolyte aggregation in dilute and semi-dilute salt-free solutions. The
      model is studied by a combination of approximate theories (random phase
      approximation and hypernetted chain theory) and numerical simulations. The
      calculated pair structure, thermodynamics, phase diagram, and polyion dynamics of
      the symmetric version of the model (the "ultrasoft restricted primitive model" or
      UPRM) differ from the corresponding properties of the widely studied "restricted
      primitive model" (RPM) where ions have hard cores. At sufficiently low
      temperatures and densities, oppositely charged polyions form weakly interacting,
      polarizable neutral pairs. The clustering probabilities, dielectric behavior, and
      electrical conductivity point to a line of sharp conductor-insulator transitions
      in the density-temperature plane. At very low temperatures, the conductor
      insulator transition line terminates near the top of a first order coexistence
      curve separating a high-density liquid phase from a low-density vapor phase. The
      simulation data hint at a tricritical behavior, reminiscent of that observed for
      the two-dimensional Coulomb gas, which contrasts with the Ising criticality of
      its three-dimensional counterpart, the RPM.

PMID- 21721651
TI  - Stability of DNA-linked nanoparticle crystals: effect of number of strands, core
      size, and rigidity of strand attachment.
AB  - Three-dimensional ordered lattices of nanoparticles (NPs) linked by DNA have
      potential applications in novel devices and materials, but most experimental
      attempts to form crystals result in amorphous packing. Here we use a coarse
      grained computational model to address three factors that impact the stability of
      bcc and fcc crystals formed by DNA-linked NPs : (i) the number of attached
      strands to the NP surface, (ii) the size of the NP core, and (iii) the rigidity
      of the strand attachment. We find that allowing mobility in the attachment of DNA
      strands to the core NP can very slightly increase or decrease melting temperature
      T(M). Larger changes to T(M) result from increasing the number of strands, which
      increases T(M), or by increasing the core NP diameter, which decreases T(M). Both
      results are consistent with experimental findings. Moreover, we show that the
      behavior of T(M) can be quantitatively described by the model introduced
      previously [F. Vargas Lara and F. W. Starr, Soft Matter, 7, 2085 (2011)].

PMID- 21721652
TI  - Reaction of aluminum clusters with water.
AB  - The atomistic mechanism of rapid hydrogen production from water by an aluminum
      cluster is investigated by ab initio molecular dynamics simulations on a parallel
      computer. A low activation-barrier mechanism of hydrogen production is found, in
      which a pair of Lewis acid and base sites on the cluster surface plays a crucial
      role. Hydrogen production is assisted by rapid proton transport in water via a
      chain of hydrogen-bond switching events similar to the Grotthuss mechanism, where
      hydroxide ions are converted to water molecules at the Lewis-acid sites and
      hydrogen atoms are supplied at the Lewis-base sites. The activation free energy
      is estimated along various reaction paths associated with hydrogen production,
      and the corresponding reaction rates are discussed based on the transition state
      theory.

PMID- 21721653
TI  - Accuracy of existing atomic potentials for the CdTe semiconductor compound.
AB  - CdTe and CdTe-based Cd(1-x)Zn(x)Te (CZT) alloys are important semiconductor
      compounds that are used in a variety of technologies including solar cells,
      radiation detectors, and medical imaging devices. Performance of such systems,
      however, is limited due to the propensity of nano- and micro-scale defects that
      form during crystal growth and manufacturing processes. Molecular dynamics
      simulations offer an effective approach to study the formation and interaction of
      atomic scale defects in these crystals, and provide insight on how to minimize
      their concentrations. The success of such a modeling effort relies on the
      accuracy and transferability of the underlying interatomic potential used in
      simulations. Such a potential must not only predict a correct trend of structures
      and energies of a variety of elemental and compound lattices, defects, and
      surfaces but also capture correct melting behavior and should be capable of
      simulating crystalline growth during vapor deposition as these processes sample a
      variety of local configurations. In this paper, we perform a detailed evaluation
      of the performance of two literature potentials for CdTe, one having the
      Stillinger-Weber form and the other possessing the Tersoff form. We examine
      simulations of structures and the corresponding energies of a variety of
      elemental and compound lattices, defects, and surfaces compared to those obtained
      from ab initio calculations and experiments. We also perform melting temperature
      calculations and vapor deposition simulations. Our calculations show that the
      Stillinger-Weber parameterization produces the correct lowest energy structure.
      This potential, however, is not sufficiently transferrable for defect studies.
      Origins of the problems of these potentials are discussed and insights leading to
      the development of a more transferrable potential suitable for molecular dynamics
      simulations of defects in CdTe crystals are provided.

PMID- 21721654
TI  - Spin transport properties of single metallocene molecules attached to single
      walled carbon nanotubes via nickel adatoms.
AB  - The spin-dependent transport properties of single ferrocene, cobaltocene, and
      nickelocene molecules attached to the sidewall of a (4,4) armchair single-walled
      carbon nanotube via a Ni adatom are investigated by using a self-consistent ab
      initio approach that combines the non-equilibrium Green's function formalism with
      the spin density functional theory. Our calculations show that the Ni adatom not
      only binds strongly to the sidewall of the nanotube, but also maintains the spin
      degeneracy and affects little the transmission around the Fermi level. When the
      Ni adatom further binds to a metallocene molecule, its density of states is
      modulated by that of the molecule and electron scattering takes place in the
      nanotube. In particular, we find that for both cobaltocene and nickelocene the
      transport across the nanotube becomes spin-polarized. This demonstrates that
      metallocene molecules and carbon nanotubes can become a promising materials
      platform for applications in molecular spintronics.

PMID- 21721655
TI  - On the stability of "non-magic" endohedrally doped Si clusters: a first
      principles sampling study of MSi16(+) (M = Ti,V,Cr).
AB  - Density-functional theory is used to study the geometric and electronic structure
      of cationic Si(16)(+) clusters with a Ti, V, or Cr dopant atom. Through unbiased
      global geometry optimization based on the basin-hopping approach, we confirm that
      a Frank-Kasper polyhedron, with the metal atom at the center, represents the
      ground-state isomer for all three systems. The endohedral cage geometry is thus
      stabilized even though only VSi(16)(+) achieves electronic shell closure within
      the prevalent spherical potential model. Our analysis of the electronic structure
      traces this diminished role of shell closure for the stabilization back to the
      adaptive capability of the metal-Si bonding, which is more the result of a
      complex hybridization than the originally proposed mere formal charge transfer.
      The resulting flexibility of the metal-Si bond can also help to stabilize "non
      magic" cage-dopant combinations, which suggests that a wider range of materials
      may eventually be cast into this useful geometry for cluster-assembled materials.

PMID- 21721656
TI  - Ion-erosion induced surface nanoporosity and nanotopography on Si.
AB  - The low-energy ion-bombardment induced surface nanotopography and the
      nanopatterning of Si has been simulated by atomistic simulations using an
      approach based on molecular dynamics (MD). In order to speed up simulations a
      reasonable cutoff in simulation time and increased cooling rates for keeping in
      hand the system temperature have been used. We get an unexpectedly rich variety
      of disordered nanopatterns formed by the self-organization of the crater rims and
      adatoms islands generated by the individual ion impacts. Our results reveal that
      the low-energy (0.5 keV impact energy) ion-sputtered Si surface is not smooth at
      the sub-20 nm length scale and deep nanoholes rule the landscape. Moreover
      substantial nanoporosity is found beneath the surface with the size range of a
      few nanometer. Scanning tunneling microscopy (STM) images are also shown obtained
      for low-fluence ion-sputtering of Si at 2 keV impact energy at 30 degrees  angle
      of incidence. STM images reveal similar features obtained by computer
      simulations: nanoholes can be seen with a few nanometer diameter. The overall
      topography landscape as well as the rms surface roughness also show similar
      features for the images obtained by STM or MD at 2 keV impact energy. The applied
      approach could make it possible the simulation of nanotopographic images at the
      molecular dynamics level of theory and could help resolve scanning probe
      microscopy images in the sub-20 nm length scale regime.

PMID- 21721657
TI  - Ab initio study of dielectric response of rippled graphene.
AB  - Ab initio calculations of dielectric function and electron energy loss (EEL)
      function of periodically rippled armchair-edged graphene were performed in the
      framework of the random-phase approximation. The bending of graphene was found to
      remove restrictions on the electron transitions being forbidden in the flat
      graphene for certain light polarization. As a result, new peaks appear in the
      optical absorption spectrum and EEL spectrum of rippled graphene. Energy
      position, intensity, and width of the peaks are sensitive to the height of out-of
      plane graphene bending that can be used in construction of graphene-based
      materials with variable transparency window.

PMID- 21721658
TI  - Effects of disordered interchain interactions on polaron dynamics in
      semiconducting polymers.
AB  - Polaron dynamics in a system of two randomly coupled polymer chains is simulated
      using a nonadiabatic evolution method. The simulations are performed within the
      framework of the Su-Schrieffer-Heeger model modified to include disordered
      interchain interactions and an external electric field. By analysing the polaron
      velocity statistically, we find that the polaron motion is determined by the
      competition between the electric field and the disordered interchain
      interactions. Polaron dynamics are classified into two types, weak-coupling
      dynamics and strong-coupling dynamics. It is found that the strength of
      interchain interactions is the dominant factor controlling charge propagation in
      weak-coupling dynamics, whereas the effects of disorder are dominant in strong
      coupling dynamics. The charge carriers tend to have higher mobility for stronger
      interchain coupling, and interchain coupling disorder can be favorable for charge
      transport depending on the coupling strength and the electric field.

PMID- 21721659
TI  - Three dimensional cross-correlation dynamic light scattering by non-ergodic
      turbid media.
AB  - We investigate dynamic light scattering by non-ergodic turbid media with an
      adapted version of the method proposed by Pusey and van Megen [Physica A 157, 705
      (1989)]. Our formulation follows the derivation of the original method by
      extending it to the three dimensional cross-correlation scheme (3DDLS). The main
      finding is an expression to obtain the dynamic structure factor from light
      scattering that takes into account the system turbidity and the peculiarities of
      the 3D geometry. From 3DDLS measurements in well-controlled solid-like systems of
      different turbidity, we confirm that our results can be interpreted reasonably
      well by the theoretical approach described here. Good agreement is found with
      earlier reported results on similar systems.

PMID- 21721660
TI  - Rotational and translational self-diffusion in concentrated suspensions of
      permeable particles.
AB  - In our recent work on concentrated suspensions of uniformly porous colloidal
      spheres with excluded volume interactions, a variety of short-time dynamic
      properties were calculated, except for the rotational self-diffusion coefficient.
      This missing quantity is included in the present paper. Using a precise
      hydrodynamic force multipole simulation method, the rotational self-diffusion
      coefficient is evaluated for concentrated suspensions of permeable particles.
      Results are presented for particle volume fractions up to 45% and for a wide
      range of permeability values. From the simulation results and earlier results for
      the first-order virial coefficient, we find that the rotational self-diffusion
      coefficient of permeable spheres can be scaled to the corresponding coefficient
      of impermeable particles of the same size. We also show that a similar scaling
      applies to the translational self-diffusion coefficient considered earlier. From
      the scaling relations, accurate analytic approximations for the rotational and
      translational self-diffusion coefficients in concentrated systems are obtained,
      useful to the experimental analysis of permeable-particle diffusion. The
      simulation results for rotational diffusion of permeable particles are used to
      show that a generalized Stokes-Einstein-Debye relation between rotational self
      diffusion coefficient and high-frequency viscosity is not satisfied.

PMID- 21721661
TI  - Coil-to-globule transition by dissipative particle dynamics simulation.
AB  - The dynamics of a collapsing polymer under a temperature quench in dilute
      solution is investigated by dissipative particles dynamics. Hydrodynamic
      interactions and many-body interaction are preserved naturally by incorporating
      explicit solvent particles in this approach. Our simulation suggests a four-stage
      collapse pathway: localized clusters formation, cluster coarsening in situ,
      coarsening involving global backbone conformation change into a crumpled globule,
      and compaction of the globule. For all the quench depths and chain lengths used
      in our study, collapse proceeds without the chain getting trapped in a metastable
      "sausage" configuration, as reported in some earlier studies. We obtain the time
      scales for each of the first three stages, as well as its scaling with the quench
      depths xi and chain lengths N. The total collapse time scales as tau(c) ~ xi(
      0.46 +/- 0.04)N(0.98 +/- 0.09), with the quench depth and degree of
      polymerization.

PMID- 21721662
TI  - Spectral collocation methods for polymer brushes.
AB  - We provide an in-depth study of pseudo-spectral numerical methods associated with
      modeling the self-assembly of molten mixed polymer brushes in the framework of
      self-consistent field theory (SCFT). SCFT of molten polymer brushes has proved
      numerically challenging in the past because of sharp features that arise in the
      self-consistent pressure field at the grafting surface due to the chain end
      tethering constraint. We show that this pressure anomaly can be reduced by
      smearing the grafting points over a narrow zone normal to the surface in an
      incompressible model, and/or by switching to a compressible model for the molten
      brush. In both cases, we use results obtained from a source (delta function)
      distribution of grafting points as a reference. At the grafting surface, we
      consider both Neumann and Dirichlet conditions, where the latter is paired with a
      masking method to mimic a confining surface. When only the density profiles and
      relative free energies of two comparison phases are of interest, either source or
      smeared distributions of grafting points can be used, but a smeared distribution
      of grafting points exhibits faster convergence with respect to the number of
      chain contour steps. Absolute free energies converge only within the smeared
      model. In addition, when a sine basis is used with the masking method and a
      smeared distribution, fewer iterations are necessary to converge the SCFT fields
      for the compressible model. The numerical methods described here and investigated
      in one-dimension will provide an enabling platform for computationally more
      demanding three-dimensional SCFT studies of a broad range of mixed polymer brush
      systems.

PMID- 21721663
TI  - Conformational study of a single molecule of poly para phenylene ethynylenes in
      dilute solutions.
AB  - The conformation of single molecules of dialkyl poly para phenylene ethynylenes
      (PPEs), electro-active polymers, is studied in solutions using molecular dynamics
      simulations. The conformation of conjugated polymers affects their electro
      optical properties and therefore is critical to their current and potential uses,
      though only limited theoretical knowledge is available regarding the factors that
      control their configuration. The present study investigates the affects of
      molecular parameters including molecular weight of the polymer and chemical
      structure of the side chains of PPEs in different solvents on the conformation of
      the polymers. The PPEs are modeled atomistically where the solvents are modeled
      both implicitly and explicitly. The study finds that PPEs assume extended
      configuration which is affected by the length of the polymer backbone and the
      nature and length of substituting side chains. While the polymer remains
      extended, local dynamics is retained and no long range correlations are observed
      within the backbone. The results are compared with scattering experiments.

PMID- 21721664
TI  - A semi-analytical description of protein folding that incorporates detailed
      geometrical information.
AB  - Much has been done to study the interplay between geometric and energetic effects
      on the protein folding energy landscape. Numerical techniques such as molecular
      dynamics simulations are able to maintain a precise geometrical representation of
      the protein. Analytical approaches, however, often focus on the energetic aspects
      of folding, including geometrical information only in an average way. Here, we
      investigate a semi-analytical expression of folding that explicitly includes
      geometrical effects. We consider a Hamiltonian corresponding to a Gaussian
      filament with structure-based interactions. The model captures local features of
      protein folding often averaged over by mean-field theories, for example, loop
      contact formation and excluded volume. We explore the thermodynamics and folding
      mechanisms of beta-hairpin and alpha-helical structures as functions of
      temperature and Q, the fraction of native contacts formed. Excluded volume is
      shown to be an important component of a protein Hamiltonian, since it both
      dominates the cooperativity of the folding transition and alters folding
      mechanisms. Understanding geometrical effects in analytical formulae will help
      illuminate the consequences of the approximations required for the study of
      larger proteins.

PMID- 21721665
TI  - Note: Perturbation theory of polymer chains revisited. I. Corrected C1 and C2
      parameters for excluded volume chains.

PMID- 21721666
TI  - Comment on "Discussion on a mechanical equilibrium condition of a sessile drop on
      a smooth solid surface" [J. Chem. Phys. 130, 144106 (2009)].

PMID- 21721667
TI  - Invited review article: measurement uncertainty of linear phase-stepping
      algorithms.
AB  - Phase retrieval techniques are widely used in optics, imaging and electronics.
      Originating in signal theory, they were introduced to interferometry around 1970.
      Over the years, many robust phase-stepping techniques have been developed that
      minimize specific experimental influence quantities such as phase step errors or
      higher harmonic components of the signal. However, optimizing a technique for a
      specific influence quantity can compromise its performance with regard to others.
      We present a consistent quantitative analysis of phase measurement uncertainty
      for the generalized linear phase stepping algorithm with nominally equal phase
      stepping angles thereby reviewing and generalizing several results that have been
      reported in literature. All influence quantities are treated on equal footing,
      and correlations between them are described in a consistent way. For the special
      case of classical N-bucket algorithms, we present analytical formulae that
      describe the combined variance as a function of the phase angle values. For the
      general Arctan algorithms, we derive expressions for the measurement uncertainty
      averaged over the full 2pi-range of phase angles. We also give an upper bound for
      the measurement uncertainty which can be expressed as being proportional to an
      algorithm specific factor. Tabular compilations help the reader to quickly assess
      the uncertainties that are involved with his or her technique.

PMID- 21721668
TI  - Ultra-broadband infrared pump-probe spectroscopy using synchrotron radiation and
      a tuneable pump.
AB  - Synchrotron infrared sources have become popular mainly because of their
      excellent broadband brilliance, which enables spectroscopically resolved spatial
      mapping of stationary objects at the diffraction limit. In this article we focus
      on an often-neglected further advantage of such sources - their unique time
      structure - to bring such broadband spectroscopy to the time domain, for studying
      dynamic phenomenon down to the 100 ps limit. We describe the ultra-broadband
      (12.5 to 1.1 MUm) Fourier transform pump-probe setup, for condensed matter
      transmission- and reflection-spectroscopy, installed at the X01DC infrared beam
      line of the Swiss Light Source (SLS). The optical pump consists of a widely
      tuneable 100 ps 1 kHz laser system, covering 94% of the 16 to 1.1 MUm range. A
      thorough description of the system is given, including (i) the vector-modulator
      providing purely electronic tuning of the pump-probe overlap up to 1 ms with sub
      ps time resolution, (ii) the 500 MHz data acquisition system interfaced with the
      experimental physics and industrial control system (EPICS) based SLS control
      system for consecutive pulse sampling, and (iii) the step-scan time-slice Fourier
      transform scheme for simultaneous recording of the dual-channel pumped, un
      pumped, and difference spectra. The typical signal/noise ratio of a single
      interferogram in a 100 ps time slice is 300 (measured during one single 140 s
      TopUp period). This signal/noise ratio is comparable to that of existing gated
      Globar pump-probe Fourier transform spectroscopy, but brings up to four orders of
      magnitude better time resolution. To showcase the utility of broadband pump-probe
      spectroscopy, we investigate a Ge-on-Si material system similar to that in which
      optically pumped direct-gap lasing was recently reported. We show that the mid
      infrared reflection-spectra can be used to determine the optically injected
      carrier density, while the mid- and near-infrared transmission-spectra can be
      used to separate the strong pump-induced absorption and inversion processes
      present at the direct-gap energy.

PMID- 21721669
TI  - An efficient setup for femtosecond stimulated Raman spectroscopy.
AB  - We present an efficient and robust setup for femtosecond stimulated Raman (FSR)
      spectroscopy with 60 fs and 10 cm(-1) resolution. Raman pulses of 0.5-5 ps are
      tunable between 450-750 nm with energies 1-10 MUJ. Experimental features of the
      setup, signal processing, and data treatment are discussed in detail to be
      readily reproduced in other labs. The setup is tested by measuring FSR spectra of
      stilbene in solution.

PMID- 21721670
TI  - Influence of intensity loss in the cavity of a folded Fabry-Perot interferometer
      on interferometric signals.
AB  - Fabry-Perot interferometer is often used for the micro-displacement, because of
      its common optical path structure being insensitive to the environmental
      disturbances. Recently, the folded Fabry-Perot interferometer has been
      investigated for displacement measurements in large ranges. The advantages of a
      folded Fabry-Perot interferometer are insensitive to the tilt angle and higher
      optical resolution. But the design of the optical cavity has become more and more
      complicated. For this reason, the intensity loss in the cavity will be an
      important parameter for the distribution of the interferometric intensity. To
      obtain a more accurate result of such interferometer utilized for displacement
      measurements, the intensity loss of the cavity in the fabricated folded Fabry
      Perot interferometer and the modified equation of the folded Fabry-Perot
      interferometer will be described. According to the theoretical and experimental
      results, the presented model is available for the analysis of displacement
      measurements by a folded Fabry-Perot interferometer.

PMID- 21721671
TI  - A flexible apparatus for attosecond photoelectron spectroscopy of solids and
      surfaces.
AB  - We describe an apparatus for attosecond photoelectron spectroscopy of solids and
      surfaces, which combines the generation of isolated attosecond extreme
      ultraviolet (XUV) laser pulses by high harmonic generation in gases with time
      resolved photoelectron detection and surface science techniques in an ultrahigh
      vacuum environment. This versatile setup provides isolated attosecond pulses with
      photon energies of up to 140 eV and few-cycle near infrared pulses for studying
      ultrafast electron dynamics in a large variety of surfaces and interfaces. The
      samples can be prepared and characterized on an atomic scale in a dedicated
      flexible surface science end station. The extensive possibilities offered by this
      apparatus are demonstrated by applying attosecond XUV pulses with a central
      photon energy of ~125 eV in an attosecond streaking experiment of a xenon
      multilayer grown on a Re(0001) substrate.

PMID- 21721672
TI  - A continuous-wave optical parametric oscillator around 5-MUm wavelength for high
      resolution spectroscopy.
AB  - We present a continuous-wave optical parametric oscillator (OPO) capable of high
      resolution spectroscopy at wavelengths between 4.8 MUm and 5.4 MUm. It is based
      on periodically poled lithium niobate (PPLN) and is singly resonant for the
      signal radiation around 1.35 MUm. Because of the strong absorption of PPLN at
      wavelengths longer than 4.5 MUm, the OPO threshold rises to the scale of several
      watts, while it produces idler powers of more than 1 mW and offers continuous
      tuning over 15 GHz. A supersonic jet spectrometer is used in combination with the
      OPO to perform measurements of the transient linear molecule Si(2)C(3) at 1968.2
      cm(-1). Fifty rovibrational transition frequencies of the nu(3) antisymmetric
      stretching mode have been determined with an accuracy on the order of 10(-4) cm(
      1), and molecular parameters for the ground and the v(3) = 1 state have been
      determined most precisely.

PMID- 21721673
TI  - High resolution short focal distance Bent Crystal Laue Analyzer for copper K edge
      x-ray absorption spectroscopy.
AB  - We have developed a compact short focal distance Bent Crystal Laue Analyzer
      (BCLA) for Cu speciation studies of biological systems with specific applications
      to cancer biology. The system provides high energy resolution and high background
      rejection. The system is composed of an aluminum block serving as a log spiral
      bender for a 15 micron thick Silicon 111 crystal and a set of soller slits. The
      energy resolution of the BCLA-about 14 eV at the Cu Kalpha line- allows
      resolution of the Cu Kalpha(1) and CuKalpha(2) lines. The system is easily
      aligned by using a set of motorized XYZ linear stages. Two operation modes are
      available: incident energy scans (IES) and emission energy scans (EES). IES
      allows scanning of the incident energy while the BCLA system is maintained at a
      preselected fixed position--typically CuKalpha(1) line. EES is used when the
      incident energy is fixed and the analyzer is scanned to provide the peak profile
      of the emission lines of Cu.

PMID- 21721674
TI  - Pound-Drever-Hall-locked, frequency-stabilized cavity ring-down spectrometer.
AB  - We describe a high sensitivity and high spectral resolution laser absorption
      spectrometer based upon the frequency-stabilized cavity ring-down spectroscopy
      (FS-CRDS) technique. We used the Pound-Drever-Hall (PDH) method to lock the probe
      laser to the high-finesse ring-down cavity. We show that the concomitant
      narrowing of the probe laser line width leads to dramatically increased ring-down
      event acquisition rates (up to 14.3 kHz), improved spectrum signal-to-noise
      ratios for weak O(2) absorption spectra at lambda = 687 nm and substantial
      increase in spectrum acquisition rates compared to implementations of FS-CRDS
      that do not incorporate high-bandwidth locking techniques. The minimum detectable
      absorption coefficient and the noise-equivalent absorption coefficient for the
      spectrometer are about 2*10(-10) cm(-1) and 7.5*10(-11) cm(-1)Hz(-1/2),
      respectively.

PMID- 21721675
TI  - Femtosecond broadband fluorescence upconversion spectroscopy: improved setup and
      photometric correction.
AB  - A setup for fluorescence upconversion spectroscopy (FLUPS) is described which has
      80 fs temporal response (fwhm) for emission in the spectral range 425-750 nm.
      Broadband phase matching is achieved with tilted gate pulses at 1340 nm.
      Background from harmonics of the gate pulse is removed and sensitivity increased
      compared to previous designs. Photometric calibration of the upconversion process
      is performed with a set of fluorescent dyes. For Coumarin 153 in methanol the
      peak position, bandwidth, and asymmetry depending on delay time are reported.

PMID- 21721676
TI  - A remote scanning Raman spectrometer for in situ measurements of works of art.
AB  - In conservation science, one of the main concerns is to extract information from
      an artistic surface without damaging it. Raman spectroscopy has emerged in recent
      years as a reliable tool for the non-destructive analysis of a wide range of
      inorganic and organic materials in works of art and archaeological objects.
      Nevertheless, the technique is still mainly limited to the analysis of micro
      samples taken from artistic surfaces. The development of an instrument able to
      perform non-contact analysis of an area of a few square centimeters aims to
      further increase the employment of this technique. This paper describes the
      development of a prototype Raman scanning spectrometer based on a diode laser, a
      2D scanning mirror stage and a custom optical system, which can map a surface of
      6 cm in diameter at a working distance of 20 cm. The device exhibits collecting
      optics with a depth of field close to 6 cm, which makes the Raman system suitable
      for the analysis of non-flat surfaces and three-dimensional objects. In addition,
      the overall dimensions and weight of the instrument have been limited in order to
      make the device transportable and, in principle, usable for in situ measurements.
      Details on the design of the device, with particular emphasis on the collecting
      optical system, and on results of the characterization tests carried out to
      assess its performances are reported. Finally, an example of an application
      involving the identification of pigments from a model painting is presented.

PMID- 21721677
TI  - Laser mass-spectrometry for online diagnosis of reactive plasmas with many
      species.
AB  - The purpose of this study is to design a diagnostic system for reactive plasma
      environment by combining molecular-beam time-of-flight (TOF) mass spectroscopy
      with laser spectroscopy technique. The combination of TOF mass spectrometers and
      pulsed lasers is favorable in the diagnosis of intermediate species distribution
      since they allow the simultaneous but separate recording of the spectra of
      different species. In the plasma system, the intermediate species in electronic
      ground state or low lying excited state is pumped to higher energy level with
      resonant laser excitation, and then, the ionization with a second laser system is
      possible which can readily be detected by the TOF analyzer. The ionization itself
      is only used as a detection mechanism for the observation of the excitation of
      these states. In this manner, the population distribution of intermediate species
      can be determined with state-selective and mass-selective feature. Also, in this
      article, a flexible data acquisition and automatic control system based on
      LABVIEW was designed to integrate all the stand-alone measurement instruments
      including a TOF spectrometer, a laser system, a high performance oscilloscope,
      and a digital delay generator into a single personal computer-based control unit.
      Moreover, a virtual Boxcar integrator with hundreds of channels has been
      developed to enhance the signal while filtering out the random noises. Finally,
      the many potentials of this technique in the application of plasma diagnosis will
      be discussed.

PMID- 21721678
TI  - A high-repetition rate scheme for synchrotron-based picosecond laser pump/x-ray
      probe experiments on chemical and biological systems in solution.
AB  - We present the extension of time-resolved optical pump/x-ray absorption
      spectroscopy (XAS) probe experiments towards data collection at MHz repetition
      rates. The use of a high-power picosecond laser operating at an integer fraction
      of the repetition rate of the storage ring allows exploitation of up to two
      orders of magnitude more x-ray photons than in previous schemes based on the use
      of kHz lasers. Consequently, we demonstrate an order of magnitude increase in the
      signal-to-noise of time-resolved XAS of molecular systems in solution. This makes
      it possible to investigate highly dilute samples at concentrations approaching
      physiological conditions for biological systems. The simplicity and compactness
      of the scheme allows for straightforward implementation at any synchrotron
      beamline and for a wide range of x-ray probe techniques, such as time-resolved
      diffraction or x-ray emission studies.

PMID- 21721679
TI  - Sensitive Faraday rotation measurement with auto-balanced photodetection.
AB  - A magneto-optic polarimetry based on auto-balanced photodetection is
      investigated. In this experiment, a commercial auto-balanced photoreceiver is
      adopted to measure the Faraday rotation of air. With a proper setup to utilize
      its noise cancellation capability, the measurement can be flexible and sensitive.
      The angular sensitivity is 2.99*10(-8) rad Hz(-1/2), which is about 2.7 times the
      shot noise limit. The measured Verdet constant of air is +1.39*10(-9) rad G(-1)
      cm(-1) at 634.8 nm. Significantly we applied a small AC current to induce the
      magnetic field, so there was no heating in the coil. In addition, a double
      current modulation scheme was used to demonstrate that there was no zero drift
      and amplifier instability in the measurement. The possibility of improvement of
      the angular sensitivity and the potential applications are also discussed.

PMID- 21721680
TI  - Compact, rugged in-chamber transmission spectrometers (7-28 keV) for the Sandia Z
      facility.
AB  - We describe a pair of time-integrated transmission spectrometers that are
      designed to survey 7-28 keV (1.9 to 0.43 A) x-ray photons produced by experiments
      on the Sandia Z pulsed power facility. Each spectrometer uses a quartz 10-11
      crystal in a Cauchois geometry with a slit to provide spatial resolution along
      one dimension. The spectrometers are located in the harsh environment of the Z
      vacuum chamber, which necessitates that their design be compact and rugged.
      Example data from calibration tests and Z experiments are shown that illustrate
      the utility of the instruments.

PMID- 21721681
TI  - Femtosecond time-resolved photoelectron spectroscopy with a vacuum-ultraviolet
      photon source based on laser high-order harmonic generation.
AB  - A laser-based tabletop approach to femtosecond time-resolved photoelectron
      spectroscopy with photons in the vacuum-ultraviolet (VUV) energy range is
      described. The femtosecond VUV pulses are produced by high-order harmonic
      generation (HHG) of an amplified femtosecond Ti:sapphire laser system. Two
      generations of the same setup and results from photoelectron spectroscopy in the
      gas phase are discussed. In both generations, a toroidal grating monochromator
      was used to select one harmonic in the photon energy range of 20-30 eV. The first
      generation of the setup was used to perform photoelectron spectroscopy in the gas
      phase to determine the bandwidth of the source. We find that our HHG source has a
      bandwidth of 140 +/- 40 meV. The second and current generation is optimized for
      femtosecond pump-probe photoelectron spectroscopy with high flux and a small spot
      size at the sample of the femtosecond probe pulses. The VUV radiation is focused
      into the interaction region with a toroidal mirror to a spot smaller than 100 *
      100 MUm(2) and the flux amounts to 10(10) photons/s at the sample at a repetition
      rate of 1 kHz. The duration of the monochromatized VUV pulses is determined to be
      120 fs resulting in an overall pump-probe time resolution of 135 +/- 5 fs. We
      show how this setup can be used to map the transient valence electronic structure
      in molecular dissociation.

PMID- 21721682
TI  - A Zeeman slower design with permanent magnets in a Halbach configuration.
AB  - We describe a simple Zeeman slower design using permanent magnets. Contrary to
      common wire-wound setups, no electric power and water cooling are required. In
      addition, the whole system can be assembled and disassembled at will. The
      magnetic field is however transverse to the atomic motion and an extra repumper
      laser is necessary. A Halbach configuration of the magnets produces a high
      quality magnetic field and no further adjustment is needed. After optimization of
      the laser parameters, the apparatus produces an intense beam of slow and cold
      (87)Rb atoms. With typical fluxes of (1-5) * 10(10) atoms/s at 30 m s(-1), our
      apparatus efficiently loads a large magneto-optical trap with more than 10(10)
      atoms in 1 s, which is an ideal starting point for degenerate quantum gas
      experiments.

PMID- 21721683
TI  - Improvement of sensitivity in high-resolution Rutherford backscattering
      spectroscopy.
AB  - The sensitivity (limit of detection) of high-resolution Rutherford backscattering
      spectroscopy (HRBS) is mainly determined by the background noise of the
      spectrometer. There are two major origins of the background noise in HRBS, one is
      the stray ions scattered from the inner wall of the vacuum chamber of the
      spectrometer and the other is the dark noise of the microchannel plate (MCP)
      detector which is commonly used as a focal plane detector of the spectrometer in
      HRBS. In order to reject the stray ions, several barriers are installed inside
      the spectrometer and a thin Mylar foil is mounted in front of the detector. The
      dark noise of the MCP detector is rejected by the coincidence measurement with
      the secondary electrons emitted from the Mylar foil upon the ion passage. After
      these improvements, the background noise is reduced by a factor of 200 at a
      maximum. The detection limit can be improved down to 10 ppm for As in Si at a
      measurement time of 1 h under ideal conditions.

PMID- 21721684
TI  - Simulations of slow positron production using a low-energy electron accelerator.
AB  - Monte Carlo simulations of slow positron production via energetic electron
      interaction with a solid target have been performed. The aim of the simulations
      was to determine the expected slow positron beam intensity from a low-energy,
      high-current electron accelerator. By simulating (a) the fast positron production
      from a tantalum electron-positron converter and (b) the positron depth deposition
      profile in a tungsten moderator, the slow positron production probability per
      incident electron was estimated. Normalizing the calculated result to the
      measured slow positron yield at the present AIST linear accelerator, the expected
      slow positron yield as a function of energy was determined. For an electron beam
      energy of 5 MeV (10 MeV) and current 240 MUA (30 MUA), production of a slow
      positron beam of intensity 5 * 10(6) s(-1) is predicted. The simulation also
      calculates the average energy deposited in the converter per electron, allowing
      an estimate of the beam heating at a given electron energy and current. For low
      energy, high-current operation the maximum obtainable positron beam intensity
      will be limited by this beam heating.

PMID- 21721685
TI  - High resolution absorption spectroscopy of exploding wire plasmas using an x
      pinch x-ray source and spherically bent crystal.
AB  - We present here the use of absorption spectroscopy of the continuum radiation
      from x-pinch-produced point x-ray sources as a diagnostic to investigate the
      properties of aluminum plasmas created by pulsed power machines. This technique
      is being developed to determine the charge state, temperature, and density as a
      function of time and space under conditions that are inaccessible to x-ray
      emission spectroscopic diagnostics. The apparatus and its characterization are
      described, and the spectrometer dispersion, magnification, and resolution are
      calculated and compared with experimental results. Spectral resolution of about
      5000 and spatial resolution of about 20 MUm are demonstrated. This spectral
      resolution is the highest available to date in an absorption experiment. The
      beneficial properties of the x-pinch x-ray source as the backlighter for this
      diagnostic are the small source size (<5 MUm), smooth continuum radiation, and
      short pulse duration (<0.1 ns). Results from a closely spaced (1 mm) exploding
      wire pair are shown and the general features are discussed.

PMID- 21721686
TI  - Upgraded multipulse laser and multipoint Thomson scattering diagnostics on EAST.
AB  - Recently a new Thomson scattering diagnostic system was upgraded in EAST tokamak
      experiment using a multipulse Nd:YAG (neodymium-yttrium aluminium garnet) laser
      and a multipoint observation volumes. This diagnostic uses a new optical laser
      alignment technique that was made to determine accurately the laser position, and
      a new lens collection system that enables the measurement of wider plasma's
      object. A composite control system made we can get the results in several
      seconds. Furthermore, a new data processing method was adopted for much exact
      results.

PMID- 21721687
TI  - Experimental investigations of silicon tetrafluoride decomposition in ECR
      discharge plasma.
AB  - The results of first experiments on the investigation of plasma of electron
      cyclotron resonance (ECR) discharge, sustained by CW radiation of technological
      gyrotron with frequency 24 GHz are considered. The parameters of nitrogen plasma
      of ECR discharge in magnetic field up to 1 T were investigated by Langmuir probe
      in the pressure range 10(-4)-10(-2) mbar under different values of microwave
      power. Depending on gas pressure and power of microwave radiation, the typical
      temperature and density of electrons could attain values of 1-5 eV and 10(11)
      10(12) cm(-3), respectively. The prospects for using of ECR discharge for plasma
      chemical decomposition of silicon tetrafluoride (SiF(4)) have been experimentally
      demonstrated. Plasma was created from SiF(4) and hydrogen (H(2)) gas mixture and
      heated by microwave radiation in ECR conditions. Using the method of mass
      spectrometry analysis of the gas at the outlet from the reactor and the weighting
      method, the content of the resultants of SiF(4) decomposition as a function of
      process parameters was investigated. It was shown that SiF(4) decomposition
      degree strongly depends on the microwave power, gas pressure in the reactor, gas
      flow rates, and can attain the value of 50%. The possible applications of PECVD
      method based on ECR discharge for production of isotopically pure elements with
      high deposition rate are discussed.

PMID- 21721688
TI  - Diamagnetic loop measurement in Korea Superconducting Tokamak Advanced Research
      machine.
AB  - Diamagnetic loop (DL), which consists of two poloidal loops inside the vacuum
      vessel, is used to measure the diamagnetic flux during a plasma discharge in the
      Korea Superconducting Tokamak Advanced Research (KSTAR) machine. The vacuum
      fluxes in the DL signal can be compensated up to 0.1 mWb by using the
      coefficients, which are obtained from experimental investigations, in the vacuum
      flux measurements during vacuum shots under same operational conditions of
      magnetic coils for plasma experiment in the KSTAR machine. The maximum error in
      the diamagnetic flux measurement due to the errors of the coefficients was
      estimated as ~0.22 mWb. From the diamagnetic flux measurements for the ohmically
      heated circular plasmas in the KSTAR machine, the stored energy agrees well with
      the estimated kinetic energy within the discrepancy of 25%. When the electron
      cyclotron heating, the neutral beam injection, and the ion cyclotron resonance
      heating are added to the ohmically heated limiter plasmas, the additional heating
      effects can be clearly observed from the increase of the stored energy evaluated
      in the DL measurement.

PMID- 21721689
TI  - A high voltage pulsed power supply for capillary discharge waveguide
      applications.
AB  - We present an all solid-state, high voltage pulsed power supply for inducing
      stable plasma formation (density ~10(18) cm(-3)) in gas-filled capillary
      discharge waveguides. The pulser (pulse duration of 1 MUs) is based on transistor
      switching and wound transmission line transformer technology. For a capillary of
      length 40 mm and diameter 265 MUm and gas backing pressure of 100 mbar, a fast
      voltage pulse risetime of 95 ns initiates breakdown at 13 kV along the capillary.
      A peak current of ~280 A indicates near complete ionization, and the r.m.s.
      temporal jitter in the current pulse is only 4 ns. Temporally stable plasma
      formation is crucial for deploying capillary waveguides as plasma channels in
      laser-plasma interaction experiments, such as the laser wakefield accelerator.

PMID- 21721690
TI  - High power millimeter wave experiment of ITER relevant electron cyclotron heating
      and current drive system.
AB  - High power, long pulse millimeter (mm) wave experiments of the RF test stand
      (RFTS) of Japan Atomic Energy Agency (JAEA) were performed. The system consists
      of a 1 MW/170 GHz gyrotron, a long and short distance transmission line (TL), and
      an equatorial launcher (EL) mock-up. The RFTS has an ITER-relevant configuration,
      i.e., consisted by a 1 MW-170 GHz gyrotron, a mm wave TL, and an EL mock-up. The
      TL is composed of a matching optics unit, evacuated circular corrugated
      waveguides, 6-miter bends, an in-line waveguide switch, and an isolation valve.
      The EL-mock-up is fabricated according to the current design of the ITER
      launcher. The Gaussian-like beam radiation with the steering capability of 20
      degrees -40 degrees  from the EL mock-up was also successfully proved. The high
      power, long pulse power transmission test was conducted with the metallic load
      replaced by the EL mock-up, and the transmission of 1 MW/800 s and 0.5 MW/1000 s
      was successfully demonstrated with no arcing and no damages. The transmission
      efficiency of the TL was 96%. The results prove the feasibility of the ITER
      electron cyclotron heating and current drive system.

PMID- 21721691
TI  - Development of a plasma generator for a long pulse ion source for neutral beam
      injectors.
AB  - A plasma generator for a long pulse H(+)/D(+) ion source has been developed. The
      plasma generator was designed to produce 65 A H(+)/D(+) beams at an energy of 120
      keV from an ion extraction area of 12 cm in width and 45 cm in length.
      Configuration of the plasma generator is a multi-cusp bucket type with SmCo
      permanent magnets. Dimension of a plasma chamber is 25 cm in width, 59 cm in
      length, and 32.5 cm in depth. The plasma generator was designed and fabricated at
      Japan Atomic Energy Agency. Source plasma generation and beam extraction tests
      for hydrogen coupling with an accelerator of the KSTAR ion source have been
      performed at the KSTAR neutral beam test stand under the agreement of Japan-Korea
      collaborative experiment. Spatial uniformity of the source plasma at the
      extraction region was measured using Langmuir probes and +/-7% of the deviation
      from an averaged ion saturation current density was obtained. A long pulse test
      of the plasma generation up to 200 s with an arc discharge power of 70 kW has
      been successfully demonstrated. The arc discharge power satisfies the requirement
      of the beam production for the KSTAR NBI. A 70 keV, 41 A, 5 s hydrogen ion beam
      has been extracted with a high arc efficiency of 0.9 -1.1 A/kW at a beam
      extraction experiment. A deuteron yield of 77% was measured even at a low beam
      current density of 73 mA/cm(2).

PMID- 21721692
TI  - Intermediate frequency band digitized high dynamic range radiometer system for
      plasma diagnostics and real-time Tokamak control.
AB  - An intermediate frequency (IF) band digitizing radiometer system in the 100-200
      GHz frequency range has been developed for Tokamak diagnostics and control, and
      other fields of research which require a high flexibility in frequency resolution
      combined with a large bandwidth and the retrieval of the full wave information of
      the mm-wave signals under investigation. The system is based on directly
      digitizing the IF band after down conversion. The enabling technology consists of
      a fast multi-giga sample analog to digital converter that has recently become
      available. Field programmable gate arrays (FPGA) are implemented to accomplish
      versatile real-time data analysis. A prototype system has been developed and
      tested and its performance has been compared with conventional electron cyclotron
      emission (ECE) spectrometer systems. On the TEXTOR Tokamak a proof of principle
      shows that ECE, together with high power injected and scattered radiation,
      becomes amenable to measurement by this device. In particular, its capability to
      measure the phase of coherent signals in the spectrum offers important advantages
      in diagnostics and control. One case developed in detail employs the FPGA in real
      time fast Fourier transform (FFT) and additional signal processing. The major
      benefit of such a FFT-based system is the real-time trade-off that can be made
      between frequency and time resolution. For ECE diagnostics this corresponds to a
      flexible spatial resolution in the plasma, with potential application in smart
      sensing of plasma instabilities such as the neoclassical tearing mode (NTM) and
      sawtooth instabilities. The flexible resolution would allow for the measurement
      of the full mode content of plasma instabilities contained within the system
      bandwidth.

PMID- 21721693
TI  - First results from the modular multi-channel dispersion interferometer at the
      TEXTOR tokamak.
AB  - At the TEXTOR tokamak in Julich, Germany, a modular dispersion interferometer was
      installed and operated for the first time. Equipped with four lines of sight, the
      line-integrated density could be measured in parallel at different major radii
      with a resolution of better than 3 * 10(17) m(-2). This paper will describe the
      setup and show the first measurement results. Among others, it was possible to
      detect the evolution of a disruption with a time resolution of 4 MUs. The
      movement of the runaway beam following the disruption could be resolved spatially
      and temporarily.

PMID- 21721694
TI  - Development of two-grating spectrometer for the charge exchange spectroscopy
      system on KSTAR.
AB  - The charge exchange spectroscopy (CES) system on Korea Superconducting Tokamak
      Advanced Research (KSTAR) was installed last year and had been applied to measure
      the C VI ion temperature and rotation velocity profiles. The ion temperature and
      rotation velocity profiles had been estimated from the C VI 5290.5 A (n = 8-7)
      charge-exchange spectrum signal measured by a Czerny-Turner type spectrometer and
      a thinned back-illuminated charge coupled device (CCD) camera. However, the
      Czerny-Turner type spectrometer used for the KSTAR CES system showed so low
      signal to noise ratio for KSTAR plasmas in the 2010 experimental campaign that
      the time resolution of the CES system had been limited to 100 ms due to the
      increased exposure time of the attached CCD camera. Then, new two-grating
      spectrometer had been developed in order to improve the time resolution of the
      CES system. The spectrometer consists of two gratings (1200 g/mm and 1800 g/mm
      each) with additive configuration, concave mirrors (f = 50 cm), and a cylindrical
      lens (f = 50 cm). The time resolution of the CES system increases by a factor of
      2-4 with the two-grating spectrometer. The C VI ion temperature and rotation
      velocity profiles obtained by the two-grating spectrometer are compared to those
      by Czerny-Turner type spectrometer in this paper.

PMID- 21721695
TI  - Upgrades to the Auburn linear experiment for instability studies.
AB  - The Auburn linear experiment for instability studies (ALEXIS) is a laboratory
      plasma physics experiment that is designed to investigate the role of spatially
      non-uniform E * B drifts using a magnetized cylindrical plasma column. This paper
      discusses the recent upgrades to the ALEXIS device, including improvements to the
      plasma source, gas management systems, and diagnostic suite.

PMID- 21721696
TI  - Voltage preamplifier for extensional quartz sensors used in scanning force
      microscopy.
AB  - Extensional-mode quartz resonators are being increasingly used as force sensors
      in dynamic scanning force microscopy or atomic force microscopy (AFM). We propose
      a voltage preamplifier in order to amplify the charge induced on quartz
      electrodes. The proposed solution has some advantages over the typically used
      current-to-voltage converters. First, the gain does not depend on the inner
      parameters of the quartz resonator, which are usually unknown for the specific
      resonator and may even vary during the measurement. Second, with such an
      amplifier a better signal-to-noise ratio can be achieved. Finally, we present AFM
      images of the Si(111) and the SiO(2) surfaces obtained by the voltage
      preamplifier with simultaneously recorded tunneling current.

PMID- 21721697
TI  - On the implementation of computed laminography using synchrotron radiation.
AB  - Hard x rays from a synchrotron source are used in this implementation of computed
      laminography for three-dimensional (3D) imaging of flat, laterally extended
      objects. Due to outstanding properties of synchrotron light, high spatial
      resolution down to the micrometer scale can be attained, even for specimens
      having lateral dimensions of several decimeters. Operating either with a
      monochromatic or with a white synchrotron beam, the method can be optimized to
      attain high sensitivity or considerable inspection throughput in synchrotron user
      and small-batch industrial experiments. The article describes the details of
      experimental setups, alignment procedures, and the underlying reconstruction
      principles. Imaging of interconnections in flip-chip and wire-bonded devices
      illustrates the peculiarities of the method compared to its alternatives and
      demonstrates the wide application potential for the 3D inspection and quality
      assessment in microsystem technology.

PMID- 21721698
TI  - Local raster scanning for high-speed imaging of biopolymers in atomic force
      microscopy.
AB  - A novel algorithm is described and illustrated for high speed imaging of
      biopolymers and other stringlike samples using atomic force microscopy. The
      method uses the measurements in real-time to steer the tip of the instrument to
      localize the scanning area over the sample of interest. Depending on the sample,
      the scan time can be reduced by an order of magnitude or more while maintaining
      image resolution. Images are generated by interpolating the non-raster data using
      a modified Kriging algorithm. The method is demonstrated using physical
      simulations that include actuator and cantilever dynamics, nonlinear tip-sample
      interactions, and measurement noise as well as through scanning experiments in
      which a two-axis nanopositioning stage is steered by the algorithm using
      simulated height data.

PMID- 21721699
TI  - Flexible drift-compensation system for precise 3D force mapping in severe drift
      environments.
AB  - The acquisition of dense 3D data sets is of great importance, but also a
      challenge for scanning probe microscopy (SPM). Thermal drift often induces severe
      distortions in the data, which usually constrains the acquisition of dense data
      sets to experiments under ultra-high vacuum and low-temperature conditions. Atom
      tracking is an elegant approach to compensate for thermal drift and to position
      the microscope tip with highest precision. Here, we present a flexible drift
      compensation system which can easily be connected to existing SPM hardware.
      Furthermore, we describe a 3D data acquisition and position correction protocol,
      which is capable of handling large and non-linear drift as typically present in
      room temperature measurements. This protocol is based on atom-tracking for
      precise positioning of the tip and we are able to acquire dense 3D data sets over
      several hours at room temperature. The performance of the protocol is
      demonstrated by presenting 3D data taken on a CaCO(3)(10 14) surface with the
      data density being as large as 85*85*500 pixel.

PMID- 21721700
TI  - Spatial filter based 3D resolution improvement and polarization properties of
      multiphoton multiple-excitation-spot-optical microscopy.
AB  - Three-dimensional (3D) resolution improvement in multi-photon multiple-excitation
      spot-optical microscopy is proposed. Specially designed spatial filter is
      employed for improving the overall 3D resolution of the imaging system. An
      improvement up to a factor of 14.5 and sub-femto liter volume excitation is
      achieved. The system shows substantial sidelobe reduction (<4%) due to the non
      linear intensity dependence of multiphoton process. Polarization effect on x
      oriented and freely rotating dipoles shows dramatic change in the field
      distribution at the focal-plane. The resulting point-spread function has the
      ability to produce several strongly localized polarization dependent field
      patterns which may find applications in optical engineering and bioimaging.

PMID- 21721701
TI  - Qplus AFM driven nanostencil.
AB  - We describe the development of a novel setup, in which large stencils with
      suspended silicon nitride membranes are combined with atomic force microscopy
      (AFM) regulation by using tuning forks. This system offers the possibility to
      perform separate AFM and nanostencil operations, as well as combined modes when
      using stencil chips with integrated tips. The flexibility and performances are
      demonstrated through a series of examples, including wide AFM scans in closed
      loop mode, probe positioning repeatability of a few tens of nanometer,
      simultaneous evaporation of large (several hundred of micron square) and
      nanoscopic metals and fullerene patterns in static, multistep, and dynamic modes.
      This approach paves the way for further developments, as it fully combines the
      advantages of conventional stenciling with the ones of an AFM driven shadow mask.

PMID- 21721702
TI  - Preparation of tips coated with poly(dimethylsiloxane) for scanning tunneling
      microscopy in aqueous solutions.
AB  - A simple and reliable method for preparing tips coated with
      poly(dimethylsiloxane) (PDMS) for scanning tunneling microscopy (STM) in aqueous
      solutions is reported. Au STM tips were dip-coated with PDMS and subsequently
      cured. The coated tips were characterized by scanning electron microscopy, energy
      dispersive x-ray spectroscopy, and voltammetry. We show that the PDMS layer
      smoothly covers the tip surface except for its very apex. These tips enable
      atomically resolved imaging of a sample surface and measurement of single
      molecule conductance below 1.0 nS with STM in aqueous solutions. Because of the
      superior compatibility of PDMS with organic solvents, the PDMS-coated tips would
      be useful for preparing molecular tips via their chemical modification in such
      solvents, enabling chemically selective imaging of a single molecule in water.

PMID- 21721703
TI  - In situ nanomechanical testing in focused ion beam and scanning electron
      microscopes.
AB  - The recent interest in size-dependent deformation of micro- and nanoscale
      materials has paralleled both technological miniaturization and advancements in
      imaging and small-scale mechanical testing methods. Here we describe a
      quantitative in situ nanomechanical testing approach adapted to a dual-beam
      focused ion beam and scanning electron microscope. A transducer based on a three
      plate capacitor system is used for high-fidelity force and displacement
      measurements. Specimen manipulation, transfer, and alignment are performed using
      a manipulator, independently controlled positioners, and the focused ion beam.
      Gripping of specimens is achieved using electron-beam assisted Pt-organic
      deposition. Local strain measurements are obtained using digital image
      correlation of electron images taken during testing. Examples showing results for
      tensile testing of single-crystalline metallic nanowires and compression of
      nanoporous Au pillars will be presented in the context of size effects on
      mechanical behavior and highlight some of the challenges of conducting
      nanomechanical testing in vacuum environments.

PMID- 21721704
TI  - Rotating sample magnetometer for cryogenic temperatures and high magnetic fields.
AB  - We report on the design and implementation of a rotating sample magnetometer
      (RSM) operating in the variable temperature insert (VTI) of a cryostat equipped
      with a high-field magnet. The limited space and the cryogenic temperatures impose
      the most critical design parameters: the small bore size of the magnet requires a
      very compact pick-up coil system and the low temperatures demand a very careful
      design of the bearings. Despite these difficulties the RSM achieves excellent
      resolution at high magnetic field sweep rates, exceeding that of a typical
      vibrating sample magnetometer by about a factor of ten. In addition the gas-flow
      cryostat and the high-field superconducting magnet provide a temperature and
      magnetic field range unprecedented for this type of magnetometer.

PMID- 21721705
TI  - High-throughput characterization of stresses in thin film materials libraries
      using Si cantilever array wafers and digital holographic microscopy.
AB  - We report the development of an advanced high-throughput stress characterization
      method for thin film materials libraries sputter-deposited on micro-machined
      cantilever arrays consisting of around 1500 cantilevers on 4-inch silicon-on
      insulator wafers. A low-cost custom-designed digital holographic microscope (DHM)
      is employed to simultaneously monitor the thin film thickness, the surface
      topography and the curvature of each of the cantilevers before and after
      deposition. The variation in stress state across the thin film materials library
      is then calculated by Stoney's equation based on the obtained radii of curvature
      of the cantilevers and film thicknesses. DHM with nanometer-scale out-of-plane
      resolution allows stress measurements in a wide range, at least from several MPa
      to several GPa. By using an automatic x-y translation stage, the local stresses
      within a 4-inch materials library are mapped with high accuracy within 10 min.
      The speed of measurement is greatly improved compared with the prior laser
      scanning approach that needs more than an hour of measuring time. A high
      throughput stress measurement of an as-deposited Fe-Pd-W materials library was
      evaluated for demonstration. The fast characterization method is expected to
      accelerate the development of (functional) thin films, e.g., (magnetic) shape
      memory materials, whose functionality is greatly stress dependent.

PMID- 21721706
TI  - First-order reversal curves acquired by a high precision ac induction
      magnetometer.
AB  - We present a setup allowing to characterize the local irreversible behavior of
      soft magnetic samples. It is achieved by modifying a conventional ac induction
      magnetometer in order to measure first-order reversal curves (FORCs), a
      magnetostatic characterization technique. The required modifications were
      performed on a home-made setup allowing high precision measurement, with
      sensibility less than 0.005 Oe for the applied field and 10(-6) emu for the
      magnetization. The main crucial point for the FORCs accuracy is the constancy of
      the applied field sweep rate, because of the magnetic viscosity. Therefore,
      instead of the common way to work at constant frequency, each FORC is acquired at
      a slightly different frequency, in order to keep the field variation constant in
      time. The obtained results exhibit the consequences of magnetic viscosity, thus
      opening up the path of studying this phenomenon for soft magnetic materials.

PMID- 21721707
TI  - A high temperature apparatus for measurement of the Seebeck coefficient.
AB  - A high temperature Seebeck coefficient measurement apparatus with various
      features to minimize typical sources of error is designed and built. Common
      sources of temperature and voltage measurement error are described and principles
      to overcome these are proposed. With these guiding principles, a high temperature
      Seebeck measurement apparatus with a uniaxial 4-point contact geometry is
      designed to operate from room temperature to over 1200 K. This instrument design
      is simple to operate, and suitable for bulk samples with a broad range of
      physical types and shapes.

PMID- 21721708
TI  - Laser dispersion and ignition of metal fuel particles.
AB  - The development of a laser-shock technique for dispersing Al metal fuel particles
      at velocities approaching those expected in a detonating explosive is discussed.
      The technique is described in detail by quantifying how air drag affects the
      temporal variation of the velocity of the dispersed particle plume. The effect of
      particle size is incorporated by examining various poly-dispersed commercial Al
      powders at different dispersion velocities (390-630 m/s). The technique is
      finally tested within a preliminary study of particle ignition delay and burn
      time, where the effect of velocity is highlighted for different particle sizes.
      It was found that plume velocity exhibits a modified exponential temporal
      profile, where smaller particles are more susceptible to air drag than larger
      ones. Moreover, larger particles exhibit longer ignition delays and burn times
      than smaller ones. The velocity of a particle was found to significantly affect
      its ignition delay, burn time, and combustion temperature, especially for
      particles in the diffusion-controlled regime. Shorter ignition delays and burn
      times and lower temperatures were observed at higher particle velocities. The
      utility of this technique as a combustion screening test for future, novel fuels
      is discussed.

PMID- 21721709
TI  - A simple dynamic optical manipulation technique for label-free detection of
      biological cells.
AB  - A dynamic optical tweezers system is employed for generation of an optical trap
      in continuous rotation for manipulating a biological cell in an aqueous solution.
      When the rotating speed is increased, the trapped cell experiences an augmented
      viscous drag force, and eventually it escapes from the trap at the critical
      rotating speed: when the drag force is greater than the trapping force. With
      experimental verifications, the method can easily be employed to differentiate
      cells in terms of trapping forces due to different refractive indices. The
      proposed method is a simple, robust, accurate and noninvasive label-free
      technique for cell detection.

PMID- 21721710
TI  - Single HeLa and MCF-7 cell measurement using minimized impedance spectroscopy and
      microfluidic device.
AB  - This study presents an impedance measurement system for single-cell capture and
      measurement. The microwell structure which utilizes nDEP force is used to single
      cell capture and a minimized impedance spectroscopy which includes a power supply
      chip, an impedance measurement chip and a USB microcontroller chip is used to
      single-cell impedance measurement. To improve the measurement accuracy of the
      proposed system, Biquadratic fitting is used in this study. The measurement
      accuracy and reliability of the proposed system are compared to those of a
      conventional precision impedance analyzer. Moreover, a stable material, latex
      beads, is used to study the impedance measurement using the minimized impedance
      spectroscopy with cell-trapping device. Finally, the proposed system is used to
      measure the impedance of HeLa cells and MCF-7 cells. The impedance of single HeLa
      cells decreased from 9.55 * 10(3) to 3.36 * 10(3) Omega and the impedance of
      single MCF-7 cells decreased from 3.48 * 10(3) to 1.45 * 10(3) Omega at an
      operate voltage of 0.5 V when the excitation frequency was increased from 11 to
      101 kHz. The results demonstrate that the proposed impedance measurement system
      successfully distinguishes HeLa cells and MCF-7 cells.

PMID- 21721712
TI  - A versatile facility for laboratory studies of viscoelastic and poroelastic
      behaviour of rocks.
AB  - Novel laboratory equipment has been modified to allow both torsional and flexural
      oscillation measurements at sub-microstrain amplitudes, thereby providing seismic
      frequency constraints on both the shear and compressional wave properties of
      cylindrical rock specimens within the linear regime. The new flexural mode
      capability has been tested on experimental assemblies containing fused silica
      control specimens. Close consistency between the experimental data and the
      results of numerical modelling with both finite-difference and finite-element
      methods demonstrates the viability of the new technique. The capability to
      perform such measurements under conditions of independently controlled confining
      and pore-fluid pressure, with emerging strategies for distinguishing between
      local (squirt) and global (specimen-wide) fluid flow, will have particular
      application to the study of frequency-dependent seismic properties expected of
      cracked and fluid-saturated rocks of the Earth's upper crust.

PMID- 21721711
TI  - A multiplexed immunoassay system based upon reciprocating centrifugal
      microfluidics.
AB  - A novel, centrifugal disk-based micro-total analysis system (MUTAS) for low cost
      and high throughput semi-automated immunoassay processing was developed. A key
      innovation in the disposable immunoassay disk design is in a fluidic structure
      that enables very efficient micro-mixing based on a reciprocating mechanism in
      which centrifugal acceleration acting upon a liquid element first generates and
      stores pneumatic energy that is then released by a reduction of the centrifugal
      acceleration, resulting in a reversal of direction of flow of the liquid. Through
      an alternating sequence of high and low centrifugal acceleration, the system
      reciprocates the flow of liquid within the disk to maximize
      incubation/hybridization efficiency between antibodies and antigen macromolecules
      during the incubation/hybridization stage of the assay. The described
      reciprocating mechanism results in a reduction in processing time and reagent
      consumption by one order of magnitude.

PMID- 21721713
TI  - The effect of a scanning flat fold mirror on a cosmic microwave background B-mode
      experiment.
AB  - We investigate the possibility of using a flat-fold beam steering mirror for a
      cosmic microwave background B-mode experiment. An aluminium flat-fold mirror is
      found to add ~0.075% polarization, which varies in a scan synchronous way. Time
      domain simulations of a realistic scanning pattern are performed, and the effect
      on the power-spectrum illustrated, and a possible method of correction applied.

PMID- 21721714
TI  - Powered oscillator using ignitron switches.
AB  - A 10-MVA-scale resonant oscillator, powered by a pulse-forming network and
      switched with a pair of commutating mercury ignitrons, was developed for the MST
      reversed-field pinch plasma-confinement experiment. A novel feature of this
      circuit is its commutation mechanism, wherein each turning on of one ignitron
      causes a reverse voltage transient that turns off the other. Two of these
      oscillators are used in oscillating-field current-drive tests, in which they are
      capable of nearly 1MW net input power to the plasma, with resonant frequencies of
      a few 100 Hz for pulse durations of a few tens of ms, being precharged for
      immediate full amplitude. We describe the circuit and its operation, and discuss
      features that allow reliable, high-current commutation of the ignitrons and
      exploit their low switching impedance.

PMID- 21721715
TI  - Frequency-shift vs phase-shift characterization of in-liquid quartz crystal
      microbalance applications.
AB  - The improvement of sensitivity in quartz crystal microbalance (QCM) applications
      has been addressed in the last decades by increasing the sensor fundamental
      frequency, following the increment of the frequency/mass sensitivity with the
      square of frequency predicted by Sauerbrey. However, this sensitivity improvement
      has not been completely transferred in terms of resolution. The decrease of
      frequency stability due to the increase of the phase noise, particularly in
      oscillators, made impossible to reach the expected resolution. A new concept of
      sensor characterization at constant frequency has been recently proposed. The
      validation of the new concept is presented in this work. An immunosensor
      application for the detection of a low molecular weight contaminant, the
      insecticide carbaryl, has been chosen for the validation. An, in principle,
      improved version of a balanced-bridge oscillator is validated for its use in
      liquids, and applied for the frequency shift characterization of the QCM
      immunosensor application. The classical frequency shift characterization is
      compared with the new phase-shift characterization concept and system proposed.

PMID- 21721716
TI  - Conductive response of a photo-excited sample in a radio-frequent driven
      resonance cavity.
AB  - An expression is derived for the perturbative response of a lumped resonance
      circuit to a sudden change in the circuit parameters. This expression is shown to
      describe also the photo-induced conductivity of a semiconductor mounted in a
      single-mode microwave cavity. The power dissipated in the cavity is measured in
      the two dimensions corresponding to time (after photo-excitation of the sample)
      and frequency (of the microwave driving source). Analysis of the experimental
      data for different semiconductor materials demonstrates the general applicability
      of the presented analytical expression here, by retrieving the time dependence of
      the sample's photo-induced conductivity.

PMID- 21721717
TI  - Low-noise high-performance current controllers for quantum cascade lasers.
AB  - Quantum cascade lasers have ushered in a new era of enhanced capability for
      chemical sensing. The higher current and voltage demands of these devices over
      their laser diode counterparts have also ushered in the demand for more capable
      drive electronics. The current-sensitivity and high frequency response of these
      devices have continued the desire for low noise, stability, and agility enjoyed
      by the laser diode community for many years. This article addresses the issue of
      maintaining these characteristics at the currents and voltages required, and
      presents example performance of current controllers developed by the author at
      Pacific Northwest National Laboratory, achieving output currents up to 2 A and
      compliance voltages of 15 V, with noise levels close to the Johnson noise of the
      internal resistors, typically a few nA/?Hz. Rapid full-depth current modulation
      up to 100 kHz is also demonstrated.

PMID- 21721718
TI  - Two-dimensional measurement of the nonlinearity parameter B/A in excised
      biological samples.
AB  - The method previously developed for measuring the acoustic nonlinearity parameter
      B/A in a liquid sample with a volume as small as 0.1 ml [S. Saito, J. Acoust.
      Soc. Am. 127, 51(2010)] has been automated and applied to two-dimensional
      measurements of excised biological samples using a LabVIEW program. The focus of
      the sound beam is laterally shifted on the 3 * 3 mm(2) area of the sample while
      measuring the B/A successively. By displaying the result of 256 time repeated
      measurements with an interval of 0.2 mm in two dimensions, a C-mode image was
      generated for B/A. The images of linear properties such as density, sound speed,
      and attenuation coefficient are also obtained. The image, whose pattern can be
      different from those of the density and sound speed, has the capability to reveal
      the detailed structure of the B/A, which varies from region to region in a single
      biological sample. The application of the method to small samples is also
      demonstrated by measuring a thermally coagulated biological sample.

PMID- 21721719
TI  - Fast fiber-optic multi-wavelength pyrometer.
AB  - A fast fiber-optic multi-wavelength pyrometer was developed for the ultraviolet
      visible-near infrared spectra from 200 nm to 1700 nm using a CCD detector and an
      InGaAs detector. The pyrometer system conveniently and quickly provides the
      sufficient choices of multiple measurement wavelengths using optical diffraction,
      which avoids the use of narrow-band filters. Flexible optical fibers are used to
      transmit the radiation so the pyrometer can be used for temperature measurements
      in harsh environments. The setup and calibrations (wavelength calibration,
      nonlinearity calibration, and radiation response calibration) of this pyrometer
      system were described. Development of the multi-wavelength pyrometer involved
      optimization of the bandwidth and temperature discrimination of the multiple
      spectra data. The analysis results showed that the wavelength intervals,
      Deltalambda(CCD) = 30 nm and Deltalambda(InGaAs) = 50 nm, are the suitable
      choices as a tradeoff between the simple emissivity model assumption and the
      multiple signal discrimination. The temperature discrimination was also
      quantificationally evaluated for various wavelengths and temperatures. The
      measurement performance of the fiber-optic multi-wavelength pyrometer was
      partially verified through measurements with a high-temperature blackbody and
      actual hot metals. This multi-wavelength pyrometer can be used for remote high
      temperature measurements.

PMID- 21721720
TI  - Improved 3-omega measurement of thermal conductivity in liquid, gases, and
      powders using a metal-coated optical fiber.
AB  - A novel 3omega thermal conductivity measurement technique called metal-coated
      3omega is introduced for use with liquids, gases, powders, and aerogels. This
      technique employs a micron-scale metal-coated glass fiber as a heater/thermometer
      that is suspended within the sample. Metal-coated 3omega exceeds alternate 3omega
      based fluid sensing techniques in a number of key metrics enabling rapid
      measurements of small samples of materials with very low thermal effusivity
      (gases), using smaller temperature oscillations with lower parasitic conduction
      losses. Its advantages relative to existing fluid measurement techniques,
      including transient hot-wire, steady-state methods, and solid-wire 3omega are
      discussed. A generalized n-layer concentric cylindrical periodic heating solution
      that accounts for thermal boundary resistance is presented. Improved sensitivity
      to boundary conductance is recognized through this model. Metal-coated 3omega was
      successfully validated through a benchmark study of gases and liquids spanning
      two-orders of magnitude in thermal conductivity.

PMID- 21721721
TI  - Simultaneous measurement of temperature and strain by combining a fiber Bragg
      grating and the pigtail fiber covered with epoxy resin.
AB  - A fiber sensor for simultaneous measurement of temperature and strain based on a
      fiber Bragg grating (FBG) with the pigtail fiber covered with epoxy resin is
      presented. The side mode suppression ratio of the FBG will vary with the
      temperature due to the Fresnel reflection from the interface between the pigtail
      fiber and the epoxy resin whose refractive index is sensitive to the temperature.
      The sensor is also capable of simultaneous measurement temperature and strain by
      combining the Bragg wavelength shift characteristics as the temperature and
      strain of the FBG.

PMID- 21721722
TI  - Development of interdigital transducer sensors for non-destructive
      characterization of thin films using high frequency Rayleigh waves.
AB  - In this paper, Rayleigh waves were generated and studied over a broad frequency
      range (5-50 MHz) and from the dispersion phenomenon, two substrate on layer type
      samples with thin layer thicknesses of 1 MUm and 500 nm, respectively, were
      characterized. The originality in this paper is the use of surface acoustic wave
      interdigital transducers (IDT) to generate surface waves as well as the
      development of a measuring device enabling an accurate estimation of the phase
      velocity to be obtained, which is essential in order to characterize such thin
      layers. Considering the excitation frequencies (5-50 MHz) and therefore the
      widths necessary on the electrodes for these types of IDT sensors (20-200 MUm), a
      lift-off procedure was chosen to deposit the electrodes on the lithium niobate
      (LiNbO(3)) piezoelectric substrates. The use of these IDT, first enabled problems
      of loss and attenuation linked to the high frequency of conventional sensors
      (wedge sensors) to be overcome and second to carry out quasi-monochromatic
      measurements in order to obtain an extremely accurate estimation of the phase
      velocity with rapid post-processing. An inverse method provided a very precise
      estimation of the thickness of the layers and the elastic constants of the
      substrate. The estimations of the thicknesses were then confirmed by measurements
      with a profilometer.

PMID- 21721723
TI  - A simply designed cell for thermal conductivity measurements of low vapor
      pressure liquids.
AB  - We have built a simply designed cell for the measurement of the thermal
      conductivity of liquids under steady state conditions from room temperature to
      about 60  degrees C. Thermal conductivities measured in the range between 0.2 and
      0.7 Wm(-1) K(-1) show deviations of a few percent from reference thermal
      conductivity data. The cell is made of two concentric parallel plates separated
      by a 0.44 mm thick sample. It is easily assembled and loaded with the sample for
      a quick and routine use.

PMID- 21721724
TI  - Thermal evaporation furnace with improved configuration for growing
      nanostructured inorganic materials.
AB  - A tubular furnace specifically designed for growing nanostructured materials is
      presented in this work. The configuration allows an accurate control of
      evaporation temperature, substrate temperature, total pressure, oxygen partial
      pressure, volumetric flow and source-substrate distance, with the possibility of
      performing both downstream and upstream depositions. In order to illustrate the
      versatility of the equipment, the furnace was used for growing semiconducting
      oxide nanostructures under different deposition conditions. Highly crystalline
      indium oxide nanowires with different morphologies were synthesized by
      evaporating mixtures of indium oxide and graphite powders with different mass
      ratios at temperatures between 900  degrees C and 1050  degrees C. The
      nanostructured layers were deposited onto oxidized silicon substrates with
      patterned gold catalyst in the temperature range from 600  degrees C to 900 
      degrees C. Gas sensors based on these nanowires exhibited enhanced sensitivity
      towards oxygen, with good response and recovery times.

PMID- 21721725
TI  - Disaggregating meteorites by automated freeze thaw.
AB  - An automated freeze-thaw (AFT) instrument for disaggregating meteorites is
      described. Meteorite samples are immersed in 18.2 MOmega water and hermetically
      sealed in a clean 30 ml Teflon vial. This vial and its contents are dipped
      between baths of liquid nitrogen and hot water over a number of cycles by a dual
      stepper motor system controlled by LabView. Uniform and periodic intervals of
      freezing and thawing induce multiple expansions and contractions, such that
      cracks propagate along natural flaws in the meteorite for a sufficient number of
      AFT cycles. For the CR2 chondrite NWA801, the boundaries between different phases
      (i.e., silicates, metal, matrix) became progressively weaker and allowed for an
      efficient recovery of 500 individual chondrules and chondrule fragments spanning
      0.2-4.7 mm diameters after 243 AFT cycles over 103.3 h. Further FT experiments on
      a basalt analog showed that the time required for freezing and thawing the same
      number of cycles can be reduced by a factor of ~4.

PMID- 21721726
TI  - Controlled vapor deposition approach to generating substrate surface
      energy/chemistry gradients.
AB  - Substrate surface energy/chemistry gradients provide a means for high-throughput
      exploration of the surface interactions that are important in many chemical and
      biological processes. We describe the implementation of a controlled vapor
      deposition approach to surface modification that enables the facile production of
      substrate surface energy/chemistry gradients while maintaining versatility in
      both the gradient profile and the surface chemistry. In our system, gradient
      formation relies on the cross-deposition of functionalized chlorosilanes onto the
      substrate surface via vaporization of the deposition materials from liquid
      reservoirs under dynamic vacuum. The effects of liquid reservoir size (reservoir
      surface area), reservoir position relative to the substrate, vacuum application,
      and volatility of the deposition materials are examined in detail and demonstrate
      the level of gradient tunability afforded by this vapor deposition approach.

PMID- 21721727
TI  - Reflection-type single long-pulse solar simulator for high-efficiency crystalline
      silicon photovoltaic modules.
AB  - Photovoltaic module measurements are predominantly taken by using pulsed solar
      simulators. However, significant errors can be generated when the existing
      simulators are applied to current high-efficiency crystalline silicon
      photovoltaic modules. This paper presents the design and implementation of a
      novel solar simulator featuring reflection-type light source and single long
      pulse flash. The analysis and experimental study of the capacitance effect and
      the technical details of the simulator including reflection-type lamp house,
      xenon flash lamp power supply, and source-measure unit are introduced. The
      results show that the complete system achieves Class AAA performance in
      accordance with the international standard. The proposed simulator outperforms
      other similar products on the market and has been adopted by some well-known
      photovoltaic module manufacturers. The practical application demonstrates that
      this high-performance and cost-effective simulator is quite suitable for
      photovoltaic module production line.

PMID- 21721728
TI  - A compact digital time differential perturbed angular correlation-spectrometer
      using field programmable gate arrays and various timestamp algorithms.
AB  - A user-friendly fully digital time differential perturbed angular correlation
      (TDPAC)-spectrometer with six detectors and fast digitizers using field
      programmable gate arrays (FPGA) is described and performance data are given. The
      new spectrometer has an online data analysis feature, a compact size, and a time
      resolution such as conventional analog spectrometers. Its calculation intensive
      part was implemented inside the digitizer. This gives the possibility to change
      parameters (energy windows, constant fraction trigger delay) and see their
      influence immediately in the gamma-gamma correlation diagrams. Tests were
      performed which showed that the time resolution using a (60)Co source with energy
      window set at 1.17 MeV and 1.33 MeV is 265 ps with LaBr(3)(Ce) scintillators and
      254 ps with BaF(2) scintillators. A true constant fraction algorithm turned out
      to be slightly better than the constant fraction of amplitude method. The
      spectrometer performance was tested with a TDPAC measurement using a (44)Ti in
      rutile source and a positron lifetime measurement using (22)Na. The maximum
      possible data rate of the spectrometer is 1.1 * 10(6) gamma quanta per detector
      and second.

PMID- 21721729
TI  - A general approach to low noise readout of terahertz imaging arrays.
AB  - This article describes the theory and design of an ultra-low noise electronic
      readout circuit for use with room temperature video-rate terahertz imaging
      arrays. First, the noise characteristics of various imaging detectors, including
      low resistance bolometers and high resistance diodes are discussed. Theoretical
      approaches to white and 1/f noise mitigation are examined, and a corresponding
      low-noise readout circuit is designed, built, and tested. It is shown that the
      circuit is capable of achieving detector limited noise performance for use in
      room temperature terahertz imaging systems. A thorough noise analysis of the
      circuit provides the necessary information for applying the readout circuit to
      any type of imaging detector, and more generally, any measurement of small
      signals from various source impedances in the presence of white and 1/f noise. W
      band measurements of an 8-element, high-resistance detector array, and a 32
      element, low-resistance detector array demonstrate the usefulness of the readout
      circuit. Finally, recommended circuit configurations for various detectors in the
      literature are provided, with theoretical performance metrics summarized.

PMID- 21721730
TI  - Five-element Johann-type x-ray emission spectrometer with a single-photon
      counting pixel detector.
AB  - A Johann-type spectrometer with five spherically bent crystals and a pixel
      detector was constructed for a range of hard x-ray photon-in photon-out
      synchrotron techniques, covering a Bragg-angle range of 60 degrees -88 degrees .
      The spectrometer provides a sub emission line width energy resolution from sub-eV
      to a few eV and precise energy calibration, better than 1.5 eV for the full range
      of Bragg angles. The use of a pixel detector allows fast and easy optimization of
      the signal-to-background ratio. A concentration detection limit below 0.4 wt% was
      reached at the Cu Kalpha(1) line. The spectrometer is designed as a modular
      mobile device for easy integration in a multi-purpose hard x-ray synchrotron
      beamline, such as the SuperXAS beamline at the Swiss Light Source.

PMID- 21721731
TI  - High-pressure and high-temperature x-ray diffraction cell for combined pressure,
      composition, and temperature measurements of hydrides.
AB  - We present the design and construction of a high-pressure (200 bars) and high
      temperature (600  degrees C) x-ray diffraction (XRD) cell for the in situ
      investigation of the hydrogen sorption of hydrides. In combination with a
      pressure, composition, and temperature system, simultaneous XRD and volumetric
      measurements become accessible. The cell consists of an x-ray semi-transparent
      hemispherical beryllium (Be) dome covering a heatable sample stage, which
      simultaneously allows sample temperatures of up to 600  degrees C in an applied
      hydrogen atmosphere of up to 200 bars. The system volume is as low as possible to
      maximize the precision of the volumetric measurements. Due to the high thermal
      conductivity of hydrogen, and in order to preserve the mechanical stability of
      the beryllium, the cell is water cooled. Its operability was studied on the
      example of the hydrogen absorption of Mg(2)Ni. The advantages and limitations of
      the proposed design are discussed.

PMID- 21721732
TI  - Development of a high pressure automated lag time apparatus for experimental
      studies and statistical analyses of nucleation and growth of gas hydrates.
AB  - Nucleation in a supercooled or a supersaturated medium is a stochastic event, and
      hence statistical analyses are required for the understanding and prediction of
      such events. The development of reliable statistical methods for quantifying
      nucleation probability is highly desirable for applications where control of
      nucleation is required. The nucleation of gas hydrates in supercooled conditions
      is one such application. We describe the design and development of a high
      pressure automated lag time apparatus (HP-ALTA) for the statistical study of gas
      hydrate nucleation and growth at elevated gas pressures. The apparatus allows a
      small volume (~150 MUl) of water to be cooled at a controlled rate in a
      pressurized gas atmosphere, and the temperature of gas hydrate nucleation, T(f),
      to be detected. The instrument then raises the sample temperature under
      controlled conditions to facilitate dissociation of the gas hydrate before
      repeating the cooling-nucleation cycle again. This process of forming and
      dissociating gas hydrates can be automatically repeated for a statistically
      significant (>100) number of nucleation events. The HP-ALTA can be operated in
      two modes, one for the detection of hydrate in the bulk of the sample, under a
      stirring action, and the other for the detection of the formation of hydrate
      films across the water-gas interface of a quiescent sample. The technique can be
      applied to the study of several parameters, such as gas pressure, cooling rate
      and gas composition, on the gas hydrate nucleation probability distribution for
      supercooled water samples.

PMID- 21721733
TI  - An ice lithography instrument.
AB  - We describe the design of an instrument that can fully implement a new
      nanopatterning method called ice lithography, where ice is used as the resist.
      Water vapor is introduced into a scanning electron microscope (SEM) vacuum
      chamber above a sample cooled down to 110 K. The vapor condenses, covering the
      sample with an amorphous layer of ice. To form a lift-off mask, ice is removed by
      the SEM electron beam (e-beam) guided by an e-beam lithography system. Without
      breaking vacuum, the sample with the ice mask is then transferred into a metal
      deposition chamber where metals are deposited by sputtering. The cold sample is
      then unloaded from the vacuum system and immersed in isopropanol at room
      temperature. As the ice melts, metal deposited on the ice disperses while the
      metals deposited on the sample where the ice had been removed by the e-beam
      remains. The instrument combines a high beam-current thermal field emission SEM
      fitted with an e-beam lithography system, cryogenic systems, and a high vacuum
      metal deposition system in a design that optimizes ice lithography for high
      throughput nanodevice fabrication. The nanoscale capability of the instrument is
      demonstrated with the fabrication of nanoscale metal lines.

PMID- 21721734
TI  - Vibration transfers to measure the performance of vibration isolated platforms on
      site using background noise excitation.
AB  - This article demonstrates a quick and easy way of quantifying the performance of
      a vibration-isolated platform. We measure the vibration transfer from floor to
      table using background noise excitation from the floor. As no excitation device
      is needed, our setup only requires two identical sensors (in our case, low noise
      accelerometers), a data acquisition system, and processing software. Background
      noise excitation from the floor has the additional advantage that any non
      linearity in the suspension system relevant to the actual vibration amplitudes
      will be taken into account. Measurement time is typically a few minutes,
      depending on the amount of background noise. The (coherent) transfer of the
      vibrations in the floor to the platform, as well as the (non-coherent) acoustical
      noise pick-up by the platform are measured. Since we use calibrated sensors, the
      absolute value of the vibration levels is established and can be expressed in
      vibration criterion curves. Transfer measurements are shown and discussed for two
      pneumatic isolated optical tables, a spring suspension system, and a simple foam
      suspension system.

PMID- 21721735
TI  - The double electrostatic ion ring experiment: a unique cryogenic electrostatic
      storage ring for merged ion-beams studies.
AB  - We describe the design of a novel type of storage device currently under
      construction at Stockholm University, Sweden, using purely electrostatic
      focussing and deflection elements, in which ion beams of opposite charges are
      confined under extreme high vacuum cryogenic conditions in separate "rings" and
      merged over a common straight section. The construction of this double
      electrostatic ion ring experiment uniquely allows for studies of interactions
      between cations and anions at low and well-defined internal temperatures and
      centre-of-mass collision energies down to about 10 K and 10 meV, respectively.
      Position sensitive multi-hit detector systems have been extensively tested and
      proven to work in cryogenic environments and these will be used to measure
      correlations between reaction products in, for example, electron-transfer
      processes. The technical advantages of using purely electrostatic ion storage
      devices over magnetic ones are many, but the most relevant are: electrostatic
      elements which are more compact and easier to construct; remanent fields,
      hysteresis, and eddy-currents, which are of concern in magnetic devices, are no
      longer relevant; and electrical fields required to control the orbit of the ions
      are not only much easier to create and control than the corresponding magnetic
      fields, they also set no upper mass limit on the ions that can be stored. These
      technical differences are a boon to new areas of fundamental experimental
      research, not only in atomic and molecular physics but also in the boundaries of
      these fields with chemistry and biology. For examples, studies of interactions
      with internally cold molecular ions will be particular useful for applications in
      astrophysics, while studies of solvated ionic clusters will be of relevance to
      aeronomy and biology.

PMID- 21721736
TI  - Note: direct measurement of the point-to-point resolution for microns-thick
      specimens in the ultrahigh-voltage electron microscope.
AB  - We report on a direct measurement method and results of the point-to-point
      resolution for microns-thick amorphous specimens in the ultrahigh-voltage
      electron microscope (ultra-HVEM). We first obtain the ultra-HVEM images of
      nanometer gold particles with different sizes on the top surfaces of the thick
      epoxy-resin specimens. Based on the Rayleigh criterion, the point-to-point
      resolution is then determined as the minimum distance between centers of two
      resolvable tangent gold particles. Some values of resolution are accordingly
      acquired for the specimens with different thicknesses at the accelerating voltage
      of 2 MV, for example, 18.5 nm and 28.4 nm for the 5 MUm and 8 MUm thick epoxy
      resin specimens, respectively. The presented method and results provide a
      reliable and useful approach to quantifying and comparing the achievable spatial
      resolution for the thick specimens imaged in the mode of transmission electron
      including the scanning transmission electron microscope.

PMID- 21721737
TI  - Note: stacked rings for terahertz wave-guiding.
AB  - We demonstrate the construction of corrugated waveguides using stacked rings to
      propagate terahertz frequencies. The waveguide allows propagation of the same
      fundamental mode as an optical-fiber, namely, the HE(11) mode. This simple
      concept opens the way for corrugated wave-guides up to several terahertz,
      maintaining beam characteristics as for terahertz applications.

PMID- 21721738
TI  - Note: study of extreme ultraviolet and soft x-ray emission of metal targets
      produced by laser-plasma-interaction.
AB  - Different metal targets were investigated as possible source material for
      tailored laser-produced plasma-sources. In the wavelength range from 1 to 20 nm,
      x-ray spectra were collected with a calibrated spectrometer with a resolution of
      lambda/Deltalambda = 150 at 1 nm up to lambda/Deltalambda = 1100 at 15 nm.
      Intense line emission features of highly ionized species as well as continuum
      like spectra from unresolved transitions are presented. With this knowledge, the
      optimal target material can be identified for the envisioned application of the
      source in x-ray spectrometry on the high energy side of the spectra at about 1
      keV. This energy is aimed for because 1 keV-radiation is ideally suited for L
      shell x-ray spectroscopy with nm-depth resolution.

PMID- 21721739
TI  - Note: high-pressure generation using nano-polycrystalline diamonds as anvil
      materials.
AB  - Nano-polycrystalline diamonds (NPDs) consist of nanosized diamond grains oriented
      in random directions. They have high toughness and isotropic mechanical
      properties. A NPD has neither the cleavage feature nor the anisotropy of hardness
      peculiar to single-crystal diamonds. Therefore, it is thought to be useful as a
      diamond anvil. We previously reported the usefulness of a NPD as an anvil for
      high-pressure development. In this study, some additional high-pressure
      generating tests using diamond anvils of various shapes prepared from NPDs were
      conducted to investigate the advantage of using NPDs for anvil applications. The
      results revealed that the achievable pressure value of a NPD anvil with a culet
      size of more than 300 MUm is about 1.5 to 2 times higher than that of single
      crystal diamond anvils, indicating that NPD anvils have considerable potential
      for large-volume diamond anvils with large culet sizes.

PMID- 21721740
TI  - Note: mounting ultra-high vacuum windows with low stress-induced birefringence.
AB  - We have developed a way to mount ultra-high vacuum windows onto standard
      ConFlat((r)) vacuum systems with very low stress-induced birefringence. Each
      window is sealed to a stainless steel flange with a compressed indium wire, and
      that flange is connected to a vacuum chamber with another indium seal. We find
      that deformation of a standard ConFlat flange during indium sealing dominates the
      stress on the window, so an extra-rigid flange is needed for minimal
      birefringence. With this mounting scheme, the typical residual birefringence is
      Deltan = 2.3 * 10(-7) and is unchanged by a 120  degrees C bake.

PMID- 21721741
TI  - Note: epitaxial ruby thin film based photonic sensor for temperature measurement.
AB  - Deposition of optical quality C-axis oriented epitaxial thin film of ruby via
      pulsed laser deposition technique on sapphire substrate is reported. The film is
      characterized by Raman spectra and photoluminescence spectra. The peak positions
      of R-line and the corresponding linewidth are observed to be temperature
      dependent. The sensitivity of R(1)-line position, upsilon, with the temperature,
      (dupsilon/dT), in the range of 138-368 K shows linear behavior confirming its
      applicability as temperature sensor.

PMID- 21721743
TI  - Design of external forces for eliminating traveling wave in a piecewise linear
      FitzHugh-Nagumo model.
AB  - Elimination and control of nonlinear phenomena in excitable media are important
      for academic interests and practical applications. This paper provides a
      systematic procedure to design external forces for eliminating a traveling wave
      in a one-dimensional piecewise linear FitzHugh-Nagumo model. This procedure
      allows us to design nonfeedback and feedback control systems. The feedback
      control systems are designed using classical control theory. Furthermore, this
      procedure is extended to a two-dimensional model and verified using numerical
      simulation.

PMID- 21721744
TI  - Average dynamics of a driven set of globally coupled excitable units.
AB  - We investigate the behavior of the order parameter describing the collective
      dynamics of a large set of driven, globally coupled excitable units. We derive
      conditions on the parameters of the system that allow to bound the degree of
      synchrony of its solutions. We describe a regime where time dependent
      nonsynchronous dynamics occurs and, yet, the average activity displays low
      dimensional, temporally complex behavior.

PMID- 21721745
TI  - Bifurcation mechanisms of regular and chaotic network signaling in brain
      astrocytes.
AB  - Bifurcation mechanisms underlying calcium oscillations in the network of
      astrocytes are investigated. Network model includes the dynamics of intracellular
      calcium concentration and intercellular diffusion of inositol 1,4,5-trisphosphate
      through gap junctions. Bifurcation analysis of underlying nonlinear dynamical
      system is presented. Parameter regions and principle bifurcation boundaries have
      been delineated and described. We show how variations of the diffusion rate can
      lead to generation of network calcium oscillations in originally nonoscillating
      cells. Different scenarios of regular activity and its transitions to chaotic
      dynamics have been obtained. Then, the bifurcations have been associated with
      statistical characteristics of calcium signals showing that different bifurcation
      scenarios yield qualitative changes in experimentally measurable quantities of
      the astrocyte activity, e.g., statistics of calcium spikes.

PMID- 21721746
TI  - Transient dynamics around unstable periodic orbits in the generalized
      repressilator model.
AB  - We study the temporal dynamics of the generalized repressilator, a network of
      coupled repressing genes arranged in a directed ring topology, and give
      analytical conditions for the emergence of a finite sequence of unstable periodic
      orbits that lead to reachable long-lived oscillating transients. Such transients
      dominate the finite time horizon dynamics that is relevant in confined, noisy
      environments such as bacterial cells (see our previous work [Strelkowa and
      Barahona, J. R. Soc. Interface 7, 1071 (2010)]), and are therefore of interest
      for bioengineering and synthetic biology. We show that the family of unstable
      orbits possesses spatial symmetries and can also be understood in terms of
      traveling wave solutions of kink-like topological defects. The long-lived
      oscillatory transients correspond to the propagation of quasistable two-kink
      configurations that unravel over a long time. We also assess the similarities
      between the generalized repressilator model and other unidirectionally coupled
      electronic systems, such as magnetic flux gates, which have been implemented
      experimentally.

PMID- 21721747
TI  - Experimental verification of synchronization in pulse-coupled oscillators with a
      refractory period and frequency distribution.
AB  - We propose herein globally pulse-coupled electronic-circuit oscillators with a
      refractory period and frequency distribution. The synchronization of such
      oscillators, which was analyzed by Konishi and Kokame [Chaos 18, 033132 (2008)],
      is verified by circuit experiments. Furthermore, we investigate a cluster state
      in the oscillators and analytically derive a simple condition to estimate the
      maximum possible number of clusters, which is confirmed by the circuit
      experiments.

PMID- 21721748
TI  - Border collision bifurcations in a two-dimensional piecewise smooth map from a
      simple switching circuit.
AB  - In recent years, the study of chaotic and complex phenomena in electronic
      circuits has been widely developed due to the increasing number of applications.
      In these studies, associated with the use of chaotic sequences, chaos is required
      to be robust (not occurring only in a set of zero measure and persistent to
      perturbations of the system). These properties are not easy to be proved, and
      numerical simulations are often used. In this work, we consider a simple
      electronic switching circuit, proposed as chaos generator. The object of our
      study is to determine the ranges of the parameters at which the dynamics are
      chaotic, rigorously proving that chaos is robust. This is obtained showing that
      the model can be studied via a two-dimensional piecewise smooth map in triangular
      form and associated with a one-dimensional piecewise linear map. The bifurcations
      in the parameter space are determined analytically. These are the border
      collision bifurcation curves, the degenerate flip bifurcations, which only are
      allowed to occur to destabilize the stable cycles, and the homoclinic
      bifurcations occurring in cyclical chaotic regions leading to chaos in 1-piece.

PMID- 21721749
TI  - Projective synchronization of two coupled excitable spiral waves.
AB  - Interaction of two identical excitable spiral waves in a bilayer system is
      studied. We find that the two spiral waves can be completely synchronized if the
      coupling strength is sufficiently large. Prior to the complete synchronization,
      we find a new type of weak synchronization between the two coupled systems, i.e.,
      the spiral wave of the driven system has the same geometric shape as the spiral
      wave of the driving system but with a much lower amplitude. This general
      behavior, called projective synchronization of two spiral waves, is similar to
      projective synchronization of two coupled nonlinear oscillators, which has been
      extensively studied before. The underlying mechanism is uncovered by the study of
      pulse collision in one-dimensional systems.

PMID- 21721750
TI  - On the topological sensitivity of cellular automata.
AB  - Ever since the conceptualization of cellular automata (CA), much attention has
      been paid to the dynamical properties of these discrete dynamical systems, and,
      more in particular, to their sensitivity to the initial condition from which they
      are evolved. Yet, the sensitivity of CA to the topology upon which they are based
      has received only minor attention, such that a clear insight in this dependence
      is still lacking and, furthermore, a quantification of this so-called topological
      sensitivity has not yet been proposed. The lack of attention for this issue is
      rather surprising since CA are spatially explicit, which means that their
      dynamics is directly affected by their topology. To overcome these shortcomings,
      we propose topological Lyapunov exponents that measure the divergence of two
      close trajectories in phase space originating from a topological perturbation,
      and we relate them to a measure grasping the sensitivity of CA to their topology
      that relies on the concept of topological derivatives, which is introduced in
      this paper. The validity of the proposed methodology is illustrated for the 256
      elementary CA and for a family of two-state irregular totalistic CA.

PMID- 21721751
TI  - Forced nonlinear resonance in a system of coupled oscillators.
AB  - We consider a resonantly perturbed system of coupled nonlinear oscillators with
      small dissipation and outer periodic perturbation. We show that for the large
      time t~E(-2) one component of the system is described for the most part by the
      inhomogeneous Mathieu equation while the other component represents pulsation of
      large amplitude. A Hamiltonian system is obtained which describes for the most
      part the behavior of the envelope in a special case. The analytic results agree
      with numerical simulations.

PMID- 21721752
TI  - Strong persistence of an attractor and generalized partial synchronization in a
      coupled chaotic system.
AB  - It is widely believed that when two discrete time chaotic systems are coupled
      together then there is a contraction in the phase space (where the essential
      dynamics takes place) when compared with the phase space in the uncoupled case.
      Contrary to such a popular belief, we produce a counter example--we consider two
      discrete time chaotic systems both with an identical attractor A, and show that
      the two systems could be nonlinearly coupled in a way such that the coupled
      system's attractor persists strongly, i.e., it is A * A despite the coupling
      strength is varied from zero to a nonzero value. To show this, we prove robust
      topological mixing on A * A. Also, it is of interest that the studied coupled
      system can exhibit a type of synchronization called generalized partial
      synchronization which is also robust.

PMID- 21721753
TI  - Bifurcation, amplitude death and oscillation patterns in a system of three
      coupled van der Pol oscillators with diffusively delayed velocity coupling.
AB  - In this paper, we study a system of three coupled van der Pol oscillators that
      are coupled through the damping terms. Hopf bifurcations and amplitude death
      induced by the coupling time delay are first investigated by analyzing the
      related characteristic equation. Then the oscillation patterns of these
      bifurcating periodic oscillations are determined and we find that there are two
      kinds of critical values of the coupling time delay: one is related to the
      synchronous periodic oscillations, the other is related to eight branches of
      asynchronous periodic solutions bifurcating simultaneously from the zero
      solution. The stability of these bifurcating periodic solutions are also
      explicitly determined by calculating the normal forms on center manifolds, and
      the stable synchronous and stable phase-locked periodic solutions are found.
      Finally, some numerical simulations are employed to illustrate and extend our
      obtained theoretical results and numerical studies also describe the switches of
      stable synchronous and phase-locked periodic oscillations.

PMID- 21721754
TI  - Exponential synchronization of chaotic systems with time-varying delays and
      parameter mismatches via intermittent control.
AB  - This paper studies the synchronization of coupled chaotic systems with time
      varying delays in the presence of parameter mismatches by means of periodically
      intermittent control. Some novel and useful quasisynchronization criteria are
      obtained by using the methods which are different from the techniques employed in
      the existing works, and the derived results are less conservative. Especially, a
      strong constraint on the control width that the control width should be larger
      than the time delay imposed by the current references is released in this paper.
      Moreover, our results show that the synchronization criteria depend on the ratio
      of control width to control period, but not the control width or the control
      period. Finally, some numerical simulations are given to show the effectiveness
      of the theoretical results.

PMID- 21721755
TI  - Desynchronization bifurcation of coupled nonlinear dynamical systems.
AB  - We analyze the desynchronization bifurcation in the coupled Rossler oscillators.
      After the bifurcation the coupled oscillators move away from each other with a
      square root dependence on the parameter. We define system transverse Lyapunov
      exponents (STLE), and in the desynchronized state one is positive while the other
      is negative. We give a simple model of coupled integrable systems with quadratic
      nonlinearity that shows a similar phenomenon. We conclude that desynchronization
      is a pitchfork bifurcation of the transverse manifold. Cubic nonlinearity also
      shows the bifurcation, but in this case the STLEs are both negative.

PMID- 21721756
TI  - Transient behavior in systems with time-delayed feedback.
AB  - We investigate the transient times for the onset of control of steady states by
      time-delayed feedback. The optimization of control by minimizing the transient
      time before control becomes effective is discussed analytically and numerically,
      and the competing influences of local and global features are elaborated. We
      derive an algebraic scaling of the transient time and confirm our findings by
      numerical simulations in dependence on feedback gain and time delay.

PMID- 21721757
TI  - Lagrangian coherent structures and the smallest finite-time Lyapunov exponent.
AB  - We point out that local minimizing curves, or troughs, of the smallest finite
      time Lyapunov exponent (FTLE) field computed over a time interval [t(0), t] and
      graphed over trajectory positions at time t mark attracting Lagrangian coherent
      structures (LCSs) at t. For two-dimensional area-preserving flows, we conclude
      that computing the largest forward-time FTLE field by itself is sufficient for
      locating both repelling LCSs at t(0) and attracting LCSs at t. We illustrate our
      results on analytic examples, as well as on a two-dimensional experimental
      velocity field measured near a swimming jellyfish.

PMID- 21721758
TI  - Time-delay-induced phase-transition to synchrony in coupled bursting neurons.
AB  - Signal transmission time delays in a network of nonlinear oscillators are known
      to be responsible for a variety of interesting dynamic behaviors including phase
      flip transitions leading to synchrony or out of synchrony. Here, we uncover that
      phase-flip transitions are general phenomena and can occur in a network of
      coupled bursting neurons with a variety of coupling types. The transitions are
      marked by nonlinear changes in both temporal and phase-space characteristics of
      the coupled system. We demonstrate these phase-transitions with Hindmarsh-Rose
      and Leech-Heart interneuron models and discuss the implications of these results
      in understanding collective dynamics of bursting neurons in the brain.

PMID- 21721759
TI  - Effect of delayed feedback on the dynamics of a scalar map via a frequency-domain
      approach.
AB  - The effect of delayed feedback on the dynamics of a scalar map is studied by
      using a frequency-domain approach. Explicit conditions for the occurrence of
      period-doubling and Neimark-Sacker bifurcations in the controlled map are found
      analytically. The appearance of a 1:2 resonance for certain values of the delay
      is also formalized, revealing that this phenomenon is independent of the system
      parameters. A detailed study of the well-known logistic map under delayed
      feedback is included for illustration.

PMID- 21721760
TI  - Dynamics of zero-Prandtl number convection near onset.
AB  - We present a detailed bifurcation scenario of zero-Prandtl number Rayleigh-Benard
      convection using direct numerical simulations (DNS) and a 27-mode low-dimensional
      model containing the most energetic modes of DNS. The bifurcation analysis
      reveals a rich variety of convective flow patterns and chaotic solutions, some of
      which are common to that of the 13-mode model of Pal et al. [EPL 87, 54003
      (2009)]. We also observed a set of periodic and chaotic wavy rolls in DNS and in
      the model similar to those observed in experiments and numerical simulations. The
      time period of the wavy rolls is closely related to the eigenvalues of the
      stability matrix of the Hopf bifurcation points at the onset of convection. This
      time period is in good agreement with the experimental results for low-Prandtl
      number fluids. The chaotic attractor of the wavy roll solutions is born through a
      quasiperiodic and phase-locking route to chaos.

PMID- 21721761
TI  - Synchronization transitions in coupled time-delay electronic circuits with a
      threshold nonlinearity.
AB  - Experimental observations of typical kinds of synchronization transitions are
      reported in unidirectionally coupled time-delay electronic circuits with a
      threshold nonlinearity and two time delays, namely feedback delay tau(1) and
      coupling delay tau(2). We have observed transitions from anticipatory to lag via
      complete synchronization and their inverse counterparts with excitatory and
      inhibitory couplings, respectively, as a function of the coupling delay tau(2).
      The anticipating and lag times depend on the difference between the feedback and
      the coupling delays. A single stability condition for all the different types of
      synchronization is found to be valid as the stability condition is independent of
      both the delays. Further, the existence of different kinds of synchronizations
      observed experimentally is corroborated by numerical simulations and from the
      changes in the Lyapunov exponents of the coupled time-delay systems.

PMID- 21721762
TI  - Synchronization of continuous complex networks based on asynchronously
      discontinuous controllers.
AB  - In this paper, our purpose is to design asynchronously discontinuous controllers
      (ADCs) to achieve the synchronization of linear coupled continuous complex
      network models (LCCNMs). The LCCNMs with ADCs are proposed for two reasons: (1)
      The controllers may not transmit their information simultaneously; (2) The
      performing process of the controllers is difficult to be active continuously. The
      synchronization is then discussed for the designed network models. Moreover, time
      delays are considered into the designed models and the synchronization is also
      presented.

PMID- 21721763
TI  - Reentrant excitation in an analog-digital hybrid circuit model of cardiac tissue.
AB  - We propose an analog-digital hybrid circuit model of one-dimensional cardiac
      tissue with hardware implementation that allows us to perform real-time
      simulations of spatially conducting cardiac action potentials. Each active nodal
      compartment of the tissue model is designed using analog circuits and a dsPIC
      microcontroller, by which the time-dependent and time-independent nonlinear
      current-voltage relationships of six types of ion channel currents employed in
      the Luo-Rudy phase I (LR-I) model for a single mammalian cardiac ventricular cell
      can be reproduced quantitatively. Here, we perform real-time simulations of
      reentrant excitation conduction in a ring-shaped tissue model that includes
      eighty nodal compartments. In particular, we show that the hybrid tissue model
      can exhibit real-time dynamics for initiation of reentries induced by uni
      directional block, as well as those for phase resetting that leads to
      annihilation of the reentry in response to impulsive current stimulations at
      appropriate nodes and timings. The dynamics of the hybrid model are comparable to
      those of a spatially distributed tissue model with LR-I compartments. Thus, it is
      conceivable that the hybrid model might be a useful tool for large scale
      simulations of cardiac tissue dynamics, as an alternative to numerical
      simulations, leading toward further understanding of the reentrant mechanisms.

PMID- 21721764
TI  - Dynamics and pattern formation in large systems of spatially-coupled oscillators
      with finite response times.
AB  - We consider systems of many spatially distributed phase oscillators that interact
      with their neighbors. Each oscillator is allowed to have a different natural
      frequency, as well as a different response time to the signals it receives from
      other oscillators in its neighborhood. Using the ansatz of Ott and Antonsen
      [Chaos 18, 037113 (2008)] and adopting a strategy similar to that employed in the
      recent work of Laing [Physica D 238, 1569 (2009)], we reduce the microscopic
      dynamics of these systems to a macroscopic partial-differential-equation
      description. Using this macroscopic formulation, we numerically find that finite
      oscillator response time leads to interesting spatiotemporal dynamical behaviors
      including propagating fronts, spots, target patterns, chimerae, spiral waves,
      etc., and we study interactions and evolutionary behaviors of these
      spatiotemporal patterns.

PMID- 21721765
TI  - Oscillons: an encounter with dynamical chaos in 1953?
AB  - We discuss the works of one of electronic art pioneers, Ben F. Laposky (1914
      2000), and argue that he might have been the first to create a family of
      essentially nonlinear analog circuits that allowed him to observe chaotic
      attractors.

PMID- 21721766
TI  - Resolving statistical uncertainty in correlation dimension estimation.
AB  - In this paper we propose a novel method for obtaining standard errors and
      confidence intervals for the correlation dimension estimated on an observed
      chaotic time series. This method is based on the U-Statistics theory and an
      ingenious combination of the moving block and parametric bootstrap procedures. We
      test the method on the basis of computer simulations for both clean and noisy
      series. We show that the distribution of the correlation dimension estimate
      obtained by our method agrees very well with the "true" distribution obtained by
      the Monte Carlo simulation. One of the main advantage of our method is the
      ability to estimate the distribution (and hence, the standard error) of the
      correlation dimension estimate using only one observed time series.

PMID- 21721767
TI  - A Lie algebraic condition for exponential stability of discrete hybrid systems
      and application to hybrid synchronization.
AB  - A Lie algebraic condition for global exponential stability of linear discrete
      switched impulsive systems is presented in this paper. By considering a Lie
      algebra generated by all subsystem matrices and impulsive matrices, when not all
      of these matrices are Schur stable, we derive new criteria for global exponential
      stability of linear discrete switched impulsive systems. Moreover, simple
      sufficient conditions in terms of Lie algebra are established for the
      synchronization of nonlinear discrete systems using a hybrid switching and
      impulsive control. As an application, discrete chaotic system's synchronization
      is investigated by the proposed method.

PMID- 21721768
TI  - Boundary-equilibrium bifurcations in piecewise-smooth slow-fast systems.
AB  - In this paper we study the qualitative dynamics of piecewise-smooth slow-fast
      systems (singularly perturbed systems) which are everywhere continuous. We
      consider phase space topology of systems with one-dimensional slow dynamics and
      one-dimensional fast dynamics. The slow manifold of the reduced system is formed
      by a piecewise-continuous curve, and the differentiability is lost across the
      switching surface. In the full system the slow manifold is no longer continuous,
      and there is an O(E) discontinuity across the switching manifold, but the
      discontinuity cannot qualitatively alter system dynamics. Revealed phase space
      topology is used to unfold qualitative dynamics of planar slow-fast systems with
      an equilibrium point on the switching surface. In this case the local dynamics
      corresponds to so-called boundary-equilibrium bifurcations, and four qualitative
      phase portraits are uncovered. Our results are then used to investigate the
      dynamics of a box model of a thermohaline circulation, and the presence of a
      boundary-equilibrium bifurcation of a fold type is shown.

PMID- 21721769
TI  - Peculiarities of the transitions to synchronization in coupled systems with
      amplitude death.
AB  - The paper presents the results of the study of the sequences of bifurcation
      leading to the synchronization and amplitude death in a system of two
      dissipatively coupled self-sustained oscillators with inertial nonlinearity. Two
      types of synchronizations tongues have been identified. In one of them phase
      locking regions exist where the synchronization is achieved by the saddle-node
      bifurcation and regions where the transition to synchronization leads through
      Neimark-Sacker bifurcation. In the second type of the tongues there are only
      phase locking regions. It has been shown that for a weak non-identity of the
      system parameters, the first type tongues merge together. The transition between
      the synchronization tongues can occur without bifurcations, i.e., transition
      between the synchronized regimes with different periods of oscillations can occur
      gradually.

PMID- 21721770
TI  - Detecting variation in chaotic attractors.
AB  - If the output of an experiment is a chaotic signal, it may be useful to detect
      small changes in the signal, but there are a limited number of ways to compare
      signals from chaotic systems, and most known methods are not robust in the
      presence of noise. One may calculate dimension or Lyapunov exponents from the
      signal, or construct a synchronizing model, but all of these are only useful in
      low noise situations. I introduce a method for detecting small variations in a
      chaotic attractor based on directly calculating the difference between vector
      fields in phase space. The differences are found by comparing close strands in
      phase space, rather than close neighbors. The use of strands makes the method
      more robust to noise and more sensitive to small attractor differences.

PMID- 21721771
TI  - Why two clocks synchronize: energy balance of the synchronized clocks.
AB  - We consider the synchronization of two clocks which are accurate (show the same
      time) but have pendulums with different masses. We show that such clocks hanging
      on the same beam beside the complete (in-phase) and antiphase synchronizations
      perform the third type of synchronization in which the difference of the
      pendulums' displacements is a periodic function of time. We identify this period
      to be a few times larger than the period of pendulums' oscillations in the case
      when the beam is at rest. Our approximate analytical analysis allows to derive
      the synchronizations conditions, explains the observed types of synchronizations,
      and gives the approximate formula for both the pendulums' amplitudes and the
      phase shift between them. We consider the energy balance in the system and show
      how the energy is transferred between pendulums via oscillating beam allowing
      pendulums' synchronization.

PMID- 21721772
TI  - Insensitive dependence of delay-induced oscillation death on complex networks.
AB  - Oscillation death (also called amplitude death), a phenomenon of coupling induced
      stabilization of an unstable equilibrium, is studied for an arbitrary symmetric
      complex network with delay-coupled oscillators, and the critical conditions for
      its linear stability are explicitly obtained. All cases including one oscillator,
      a pair of oscillators, regular oscillator networks, and complex oscillator
      networks with delay feedback coupling, can be treated in a unified form. For an
      arbitrary symmetric network, we find that the corresponding smallest eigenvalue
      of the Laplacian lambda(N) (0 >lambda(N) >= -1) completely determines the death
      island, and as lambda(N) is located within the insensitive parameter region for
      nearly all complex networks, the death island keeps nearly the largest and does
      not sensitively depend on the complex network structures. This insensitivity
      effect has been tested for many typical complex networks including Watts-Strogatz
      (WS) and Newman-Watts (NW) small world networks, general scale-free (SF)
      networks, Erdos-Renyi (ER) random networks, geographical networks, and networks
      with community structures and is expected to be helpful for our understanding of
      dynamics on complex networks.

PMID- 21721773
TI  - An elementary model of torus canards.
AB  - We study the recently observed phenomena of torus canards. These are a higher
      dimensional generalization of the classical canard orbits familiar from planar
      systems and arise in fast-slow systems of ordinary differential equations in
      which the fast subsystem contains a saddle-node bifurcation of limit cycles.
      Torus canards are trajectories that pass near the saddle-node and subsequently
      spend long times near a repelling branch of slowly varying limit cycles. In this
      article, we carry out a study of torus canards in an elementary third-order
      system that consists of a rotated planar system of van der Pol type in which the
      rotational symmetry is broken by including a phase-dependent term in the slow
      component of the vector field. In the regime of fast rotation, the torus canards
      behave much like their planar counterparts. In the regime of slow rotation, the
      phase dependence creates rich torus canard dynamics and dynamics of mixed mode
      type. The results of this elementary model provide insight into the torus canards
      observed in a higher-dimensional neuroscience model.

PMID- 21721774
TI  - From collective periodic running states to completely chaotic synchronised states
      in coupled particle dynamics.
AB  - We consider the damped and driven dynamics of two interacting particles evolving
      in a symmetric and spatially periodic potential. The latter is exerted to a time
      periodic modulation of its inclination. Our interest is twofold: First, we deal
      with the issue of chaotic motion in the higher-dimensional phase space. To this
      end, a homoclinic Melnikov analysis is utilised assuring the presence of
      transverse homoclinic orbits and homoclinic bifurcations for weak coupling
      allowing also for the emergence of hyperchaos. In contrast, we also prove that
      the time evolution of the two coupled particles attains a completely synchronised
      (chaotic) state for strong enough coupling between them. The resulting "freezing
      of dimensionality" rules out the occurrence of hyperchaos. Second, we address
      coherent collective particle transport provided by regular periodic motion. A
      subharmonic Melnikov analysis is utilised to investigate persistence of periodic
      orbits. For directed particle transport mediated by rotating periodic motion, we
      present exact results regarding the collective character of the running solutions
      entailing the emergence of a current. We show that coordinated energy exchange
      between the particles takes place in such a manner that they are enabled to
      overcome--one particle followed by the other--consecutive barriers of the
      periodic potential resulting in collective directed motion.

PMID- 21721775
TI  - Vibrational resonance in feedforward network.
AB  - This paper investigates vibrational resonance in multi-layer feedforward network
      (FFN) based on FitzHugh-Nagumo (FHN) neuron model. High-frequency stimuli can
      improve the input-output linearity of firing rates, especially for the inputs
      with low firing rate. For FFN network, it is found that high-frequency
      disturbances play important roles in enhancing the propagation of weak signal
      through layers. Synfire-enhanced phenomenon of signal propagation is also
      observed in multi-layers network, when the signal transmission is affected by
      high-frequency disturbances. Network connections are found to be important for
      the propagation of weak signal. Besides that, the characteristics of high
      frequency stimuli such as heterogeneity and frequency can also modulate the
      propagation of neural code through layers.

PMID- 21721776
TI  - Relaxation properties in classical diamagnetism.
AB  - It is an old result of Bohr that, according to classical statistical mechanics,
      at equilibrium a system of electrons in a static magnetic field presents no
      magnetization. Thus a magnetization can occur only in an out of equilibrium
      state, such as that produced through the Foucault currents when a magnetic field
      is switched on. It was suggested by Bohr that, after the establishment of such a
      nonequilibrium state, the system of electrons would quickly relax back to
      equilibrium. In the present paper, we study numerically the relaxation to
      equilibrium in a modified Bohr model, which is mathematically equivalent to a
      billiard with obstacles, immersed in a magnetic field that is adiabatically
      switched on. We show that it is not guaranteed that equilibrium is attained
      within the typical time scales of microscopic dynamics. Depending on the values
      of the parameters, one has a relaxation either to equilibrium or to a diamagnetic
      (presumably metastable) state. The analogy with the relaxation properties in the
      Fermi Pasta Ulam problem is also pointed out.

PMID- 21721777
TI  - Kinetic models of the interference of gene transcription to ncRNA and mRNA.
AB  - The experiments indicate that the transcription of genes into ncRNA can
      positively or negatively interfere with transcription into mRNA. We propose two
      kinetic models describing this effect. The first model is focused on the ncRNA
      induced chromatin modification facilitating the transcription of the downstream
      gene into mRNA. The second model includes the competition between the
      transcription into ncRNA and the binding of activator to a regulatory site of the
      downstream gene transcribed into mRNA. Our analysis based on the mean-field
      kinetic equations and Monte Carlo simulations shows the likely dependences of the
      transcription rate on RNA polymerase concentration in situations with different
      rate-limiting steps. Our models can also be used to scrutinize the dependence of
      the transcription rate on other kinetic parameters. Our kinetic Monte Carlo
      simulations show that the first model predicts stochastic bursts in the mRNA
      formation provided that the transcription into ncRNA is slow, while the second
      model predicts in addition anti-phase stochastic bursts in the mRNA and ncRNA
      formation provided that that the protein attachment to and detachment from a
      regulatory site is slow.

PMID- 21721778
TI  - Signal design using nonlinear oscillators and evolutionary algorithms:
      application to phase-locked loop disruption.
AB  - This work describes an approach for efficiently shaping the response
      characteristics of a fixed dynamical system by forcing with a designed input. We
      obtain improved inputs by using an evolutionary algorithm to search a space of
      possible waveforms generated by a set of nonlinear, ordinary differential
      equations (ODEs). Good solutions are those that result in a desired system
      response subject to some input efficiency constraint, such as signal power. In
      particular, we seek to find inputs that best disrupt a phase-locked loop (PLL).
      Three sets of nonlinear ODEs are investigated and found to have different
      disruption capabilities against a model PLL. These differences are explored and
      implications for their use as input signal models are discussed. The PLL was
      chosen here as an archetypal example but the approach has broad applicability to
      any input/output system for which a desired input cannot be obtained
      analytically.

PMID- 21721779
TI  - Introduction to Focus Issue: synchronization and cascading processes in complex
      networks.
AB  - The study of collective dynamics in complex networks has emerged as a next
      frontier in the science of networks. This Focus Issue presents the latest
      developments on this exciting front, focusing in particular on synchronous and
      cascading dynamics, which are ubiquitous forms of network dynamics found in a
      wide range of physical, biological, social, and technological systems.

PMID- 21721780
TI  - Coordinated scheduling of electricity and natural gas infrastructures with a
      transient model for natural gas flow.
AB  - This paper focuses on transient characteristics of natural gas flow in the
      coordinated scheduling of security-constrained electricity and natural gas
      infrastructures. The paper takes into account the slow transient process in the
      natural gas transmission systems. Considering their transient characteristics,
      natural gas transmission systems are modeled as a set of partial differential
      equations (PDEs) and algebraic equations. An implicit finite difference method is
      applied to approximate PDEs by difference equations. The coordinated scheduling
      of electricity and natural gas systems is described as a bi-level programming
      formulation from the independent system operator's viewpoint. The objective of
      the upper-level problem is to minimize the operating cost of electric power
      systems while the natural gas scheduling optimization problem is nested within
      the lower-level problem. Numerical examples are presented to verify the
      effectiveness of the proposed solution and to compare the solutions for steady
      state and transient models of natural gas transmission systems.

PMID- 21721781
TI  - The dynamics of network coupled phase oscillators: an ensemble approach.
AB  - We consider the dynamics of many phase oscillators that interact through a
      coupling network. For a given network connectivity we further consider an
      ensemble of such systems where, for each ensemble member, the set of oscillator
      natural frequencies is independently and randomly chosen according to a given
      distribution function. We then seek a statistical description of the dynamics of
      this ensemble. Use of this approach allows us to apply the recently developed
      ansatz of Ott and Antonsen [Chaos 18, 037113 (2008)] to the marginal distribution
      of the ensemble of states at each node. This, in turn, results in a reduced set
      of ordinary differential equations determining these marginal distribution
      functions. The new set facilitates the analysis of network dynamics in several
      ways: (i) the time evolution of the reduced system of ensemble equations is much
      smoother, and thus numerical solutions can be obtained much faster by use of
      longer time steps; (ii) the new set of equations can be used as a basis for
      obtaining analytical results; and (iii) for a certain type of network, a
      reduction to a low dimensional description of the entire network dynamics is
      possible. We illustrate our approach with numerical experiments on a network
      version of the classical Kuramoto problem, first with a unimodal frequency
      distribution, and then with a bimodal distribution. In the latter case, the
      network dynamics is characterized by bifurcations and hysteresis involving a
      variety of steady and periodic attractors.

PMID- 21721782
TI  - Reconstructing phase dynamics of oscillator networks.
AB  - We generalize our recent approach to the reconstruction of phase dynamics of
      coupled oscillators from data [B. Kralemann et al., Phys. Rev. E 77, 066205
      (2008)] to cover the case of small networks of coupled periodic units. Starting
      from a multivariate time series, we first reconstruct genuine phases and then
      obtain the coupling functions in terms of these phases. Partial norms of these
      coupling functions quantify directed coupling between oscillators. We illustrate
      the method by different network motifs for three coupled oscillators and for
      random networks of five and nine units. We also discuss nonlinear effects in
      coupling.

PMID- 21721783
TI  - Sample-to-sample fluctuations in real-network ensembles.
AB  - Network modeling based on ensemble averages tacitly assumes that the networks
      meant to be modeled are typical in the ensemble. Previous research on network
      eigenvalues, which govern a range of dynamical phenomena, has shown that this is
      indeed the case for uncorrelated networks with minimum degree >= 3. Here, we
      focus on real networks, which generally have both structural correlations and low
      degree nodes. We show that: (i) the ensemble distribution of the dynamically most
      important eigenvalues can be not only broad and far apart from the real
      eigenvalue but also highly structured, often with a multimodal rather than a bell
      shaped form; (ii) these interesting properties are found to be due to low-degree
      nodes, mainly those with degree <= 3, and network communities, which is a common
      form of structural correlation found in real networks. In addition to having
      implications for ensemble-based approaches, this shows that low-degree nodes may
      have a stronger influence on collective dynamics than previously anticipated from
      the study of computer-generated networks.

PMID- 21721784
TI  - Synchronization in interdependent networks.
AB  - We explore the synchronization behavior in interdependent systems, where the one
      dimensional (1D) network (the intranetwork coupling strength J(I)) is
      ferromagnetically intercoupled (the strength J) to the Watts-Strogatz (WS) small
      world network (the intranetwork coupling strength J(II)). In the absence of the
      internetwork coupling (J=0), the former network is well known not to exhibit the
      synchronized phase at any finite coupling strength, whereas the latter displays
      the mean-field transition. Through an analytic approach based on the mean-field
      approximation, it is found that for the weakly coupled 1D network (J(I)?1) the
      increase of J suppresses synchrony, because the nonsynchronized 1D network
      becomes a heavier burden for the synchronization process of the WS network. As
      the coupling in the 1D network becomes stronger, it is revealed by the
      renormalization group (RG) argument that the synchronization is enhanced as J(I)
      is increased, implying that the more enhanced partial synchronization in the 1D
      network makes the burden lighter. Extensive numerical simulations confirm these
      expected behaviors, while exhibiting a reentrant behavior in the intermediate
      range of J(I). The nonmonotonic change of the critical value of J(II) is also
      compared with the result from the numerical RG calculation.

PMID- 21721785
TI  - Cascading dynamics in complex quantum networks.
AB  - Recently, small-scale quantum communication has been realized by transporting
      entangled photons, rendering potentially feasible quantum networks on large
      scales. We propose a class of quantum networks comprising quantum repeaters for
      long-distance information transport and local networks of fibers and switches. As
      the transmitting capability is limited by the node bandwidth, photon loss can
      occur through the dynamical process of cascading when the network is under
      external perturbations. We obtain results that can be used to guide quantum
      network design to minimize the photon loss.

PMID- 21721786
TI  - Onset of synchronization in weighted complex networks: the effect of weight
      degree correlation.
AB  - By numerical simulations, we investigate the onset of synchronization of
      networked phase oscillators under two different weighting schemes. In scheme-I,
      the link weights are correlated to the product of the degrees of the connected
      nodes, so this kind of networks is named as the weight-degree correlated (WDC)
      network. In scheme-II, the link weights are randomly assigned to each link
      regardless of the node degrees, so this kind of networks is named as the weight
      degree uncorrelated (WDU) network. Interestingly, it is found that by increasing
      a parameter that governs the weight distribution, the onset of synchronization in
      WDC network is monotonically enhanced, while in WDU network there is a reverse in
      the synchronization performance. We investigate this phenomenon from the
      viewpoint of gradient network, and explain the contrary roles of coupling
      gradient on network synchronization: gradient promotes synchronization in WDC
      network, while deteriorates synchronization in WDU network. The findings
      highlight the fact that, besides the link weight, the correlation between the
      weight and the node degree is also important to the network dynamics.

PMID- 21721787
TI  - Local synchronization in complex networks of coupled oscillators.
AB  - We investigate the effects that network topology, natural frequency distribution,
      and system size have on the path to global synchronization as the overall
      coupling strength between oscillators is increased in a Kuramoto network. In
      particular, we study the scenario recently found by Gomez-Gardenes et al. [Phys.
      Rev. E 73, 056124 (2006)] in which macroscopic global synchronization emerges
      through a process whereby many small synchronized clusters form, grow, and merge,
      eventually leading to a macroscopic giant synchronized component. Our main result
      is that this scenario is robust to an increase in the number of oscillators or a
      change in the distribution function of the oscillators' natural frequencies, but
      becomes less prominent as the number of links per oscillator increases.

PMID- 21721788
TI  - On the topology of synchrony optimized networks of a Kuramoto-model with non
      identical oscillators.
AB  - We study synchrony optimized networks. In particular, we focus on the Kuramoto
      model with non-identical native frequencies on a random graph. In a first step,
      we generate synchrony optimized networks using a dynamic breeding algorithm,
      whereby an initial network is successively rewired toward increased
      synchronization. These networks are characterized by a large anti-correlation
      between neighbouring frequencies. In a second step, the central part of our
      paper, we show that synchrony optimized networks can be generated much more cost
      efficiently by minimization of an energy-like quantity E and subsequent random
      rewires to control the average path length. We demonstrate that synchrony
      optimized networks are characterized by a balance between two opposing structural
      properties: A large number of links between positive and negative frequencies of
      equal magnitude and a small average path length. Remarkably, these networks show
      the same synchronization behaviour as those networks generated by the dynamic
      rewiring process. Interestingly, synchrony-optimized network also exhibit
      significantly enhanced synchronization behaviour for weak coupling, below the
      onset of global synchronization, with linear growth of the order parameter with
      increasing coupling strength. We identify the underlying dynamical and
      topological structures, which give rise to this atypical local synchronization,
      and provide a simple analytical argument for its explanation.

PMID- 21721789
TI  - Phase clustering in complex networks of delay-coupled oscillators.
AB  - We study the clusterization of phase oscillators coupled with delay in complex
      networks. For the case of diffusive oscillators, we formulate the equations
      relating the topology of the network and the phases and frequencies of the
      oscillators (functional response). We solve them exactly in directed networks for
      the case of perfect synchronization. We also compare the reliability of the
      solution of the linear system for non-linear couplings. Taking advantage of the
      form of the solution, we propose a frequency adaptation rule to achieve perfect
      synchronization. We also propose a mean-field theory for uncorrelated random
      networks that proves to be pretty accurate to predict phase synchronization in
      real topologies, as for example, the Caenorhabditis elegans or the autonomous
      systems connectivity.

PMID- 21721790
TI  - Comment on "Long time evolution of phase oscillator systems" [Chaos 19, 023117
      (2009)].
AB  - In a recent paper by Ott and Antonsen [Chaos 19, 023117 (2009)], it was shown for
      the case of Lorentzian distributions of oscillator frequencies that the dynamics
      of a very general class of large systems of coupled phase oscillators time
      asymptotes to a particular simplified form given by Ott and Antonsen [Chaos 18,
      037113 (2008)]. This comment extends this previous result to a broad class of
      oscillator distribution functions.

PMID- 21721791
TI  - Breakdown of order preservation in symmetric oscillator networks with pulse
      coupling.
AB  - Symmetric networks of coupled dynamical units exhibit invariant subspaces with
      two or more units synchronized. In time-continuously coupled systems, these
      invariant sets constitute barriers for the dynamics. For networks of units with
      local dynamics defined on the real line, this implies that the units' ordering is
      preserved and that their winding number is identical. Here, we show that in
      permutation-symmetric networks with pulse-coupling, the order is often no longer
      preserved. We analytically study a class of pulse-coupled oscillators
      (characterizing for instance the dynamics of spiking neural networks) and derive
      quantitative conditions for the breakdown of order preservation. We find that in
      general pulse-coupling yields additional dimensions to the state space such that
      units may change their order by avoiding the invariant sets. We identify a system
      of two symmetrically pulse-coupled identical oscillators where, contrary to
      intuition, the oscillators' average frequencies and thus their winding numbers
      are different.

PMID- 21721792
TI  - Multiobjective synchronization of coupled systems.
AB  - In this paper, multiobjective synchronization of chaotic systems is investigated
      by especially simultaneously minimizing optimization of control cost and
      convergence speed. The coupling form and coupling strength are optimized by an
      improved multiobjective evolutionary approach that includes a hybrid chromosome
      representation. The hybrid encoding scheme combines binary representation with
      real number representation. The constraints on the coupling form are also
      considered by converting the multiobjective synchronization into a multiobjective
      constraint problem. In addition, the performances of the adaptive learning method
      and non-dominated sorting genetic algorithm-II as well as the effectiveness and
      contributions of the proposed approach are analyzed and validated through the
      Rossler system in a chaotic or hyperchaotic regime and delayed chaotic neural
      networks.

PMID- 21721793
TI  - Social influencing and associated random walk models: Asymptotic consensus times
      on the complete graph.
AB  - We investigate consensus formation and the asymptotic consensus times in stylized
      individual- or agent-based models, in which global agreement is achieved through
      pairwise negotiations with or without a bias. Considering a class of individual
      based models on finite complete graphs, we introduce a coarse-graining approach
      (lumping microscopic variables into macrostates) to analyze the ordering dynamics
      in an associated random-walk framework. Within this framework, yielding a linear
      system, we derive general equations for the expected consensus time and the
      expected time spent in each macro-state. Further, we present the asymptotic
      solutions of the 2-word naming game and separately discuss its behavior under the
      influence of an external field and with the introduction of committed agents.

PMID- 21721794
TI  - Adaptive bridge control strategy for opinion evolution on social networks.
AB  - In this paper, we present an efficient opinion control strategy for complex
      networks, in particular, for social networks. The proposed adaptive bridge
      control (ABC) strategy calls for controlling a special kind of nodes named bridge
      and requires no knowledge of the node degrees or any other global or local
      knowledge, which are necessary for some other immunization strategies including
      targeted immunization and acquaintance immunization. We study the efficiency of
      the proposed ABC strategy on random networks, small-world networks, scale-free
      networks, and the random networks adjusted by the edge exchanging method. Our
      results show that the proposed ABC strategy is efficient for all of these four
      kinds of networks. Through an adjusting clustering coefficient by the edge
      exchanging method, it is found out that the efficiency of our ABC strategy is
      closely related with the clustering coefficient. The main contributions of this
      paper can be listed as follows: (1) A new high-order social network is proposed
      to describe opinion dynamic. (2) An algorithm, which does not require the
      knowledge of the nodes' degree and other global/local network structure
      information, is proposed to control the "bridges" more accurately and further
      control the opinion dynamics of the social networks. The efficiency of our ABC
      strategy is illustrated by numerical examples. (3) The numerical results indicate
      that our ABC strategy is more efficient for networks with higher clustering
      coefficient.

PMID- 21721795
TI  - Effects of network topology, transmission delays, and refractoriness on the
      response of coupled excitable systems to a stochastic stimulus.
AB  - We study the effects of network topology on the response of networks of coupled
      discrete excitable systems to an external stochastic stimulus. We extend recent
      results that characterize the response in terms of spectral properties of the
      adjacency matrix by allowing distributions in the transmission delays and in the
      number of refractory states and by developing a nonperturbative approximation to
      the steady state network response. We confirm our theoretical results with
      numerical simulations. We find that the steady state response amplitude is
      inversely proportional to the duration of refractoriness, which reduces the
      maximum attainable dynamic range. We also find that transmission delays alter the
      time required to reach steady state. Importantly, neither delays nor
      refractoriness impact the general prediction that criticality and maximum dynamic
      range occur when the largest eigenvalue of the adjacency matrix is unity.

PMID- 21721796
TI  - Towards noncontact skin melanoma selection by multispectral imaging analysis.
AB  - A clinical trial comprising 334 pigmented and vascular lesions has been performed
      in three Riga clinics by means of multispectral imaging analysis. The imaging
      system Nuance 2.4 (CRi) and self-developed software for mapping of the main skin
      chromophores were used. Specific features were observed and analyzed for
      malignant skin melanomas: notably higher absorbance (especially as the difference
      of optical density relative to the healthy skin), uneven chromophore distribution
      over the lesion area, and the possibility to select the "melanoma areas" in the
      correlation graphs of chromophores. The obtained results indicate clinical
      potential of this technology for noncontact selection of melanoma from other
      pigmented and vascular skin lesions.

PMID- 21721797
TI  - Quantitative cell imaging using single beam phase retrieval method.
AB  - Quantitative three-dimensional imaging of cells can provide important information
      about their morphology as well as their dynamics, which will be useful in
      studying their behavior under various conditions. There are several microscopic
      techniques to image unstained, semi-transparent specimens, by converting the
      phase information into intensity information. But most of the quantitative phase
      contrast imaging techniques is realized either by using interference of the
      object wavefront with a known reference beam or using phase shifting
      interferometry. A two-beam interferometric method is challenging to implement
      especially with low coherent sources and it also requires a fine adjustment of
      beams to achieve high contrast fringes. In this letter, the development of a
      single beam phase retrieval microscopy technique for quantitative phase contrast
      imaging of cells using multiple intensity samplings of a volume speckle field in
      the axial direction is described. Single beam illumination with multiple
      intensity samplings provides fast convergence and a unique solution of the object
      wavefront. Three-dimensional thickness profiles of different cells such as red
      blood cells and onion skin cells were reconstructed using this technique with an
      axial resolution of the order of several nanometers.

PMID- 21721798
TI  - Angular high-speed massively parallel detection spectral-domain optical coherence
      tomography for speckle reduction.
AB  - We demonstrate speckle reduction based on angular compounding using parallel
      detection spectral-domain optical coherence tomography (OCT). An ultrahigh-speed
      two-dimensional complementary metal-oxide semiconductor camera acquired angular
      and spectral interference fringes (128 * 1024 pixels) simultaneously at 15,000
      frames/s for a single lateral point. A signal-to-noise ratio improvement of 8 dB
      was achieved for imaging human skin in vivo by averaging 121 angle-resolved OCT
      images.

PMID- 21721799
TI  - Novel combined miniature optical coherence tomography ultrasound probe for in
      vivo intravascular imaging.
AB  - We have developed a miniature integrated optical coherence tomography (OCT)
      ultrasound (US) probing system for intravascular imaging applications. In the OCT
      probe, the light coming out of a single mode fiber is focused by a gradient-index
      lens and then reflected by a right-angle prism from the side of the probe into
      the sample. It was combined with a 35 MHz PMN-PT side-viewing ultrasound
      transducer to obtain the ultrasound image as well. The OCT and ultrasound probes
      were integrated as a single probe to obtain OCT and ultrasound images
      simultaneously. The integrated probe has an outer diameter of 0.69 mm which, to
      our knowledge, is the smallest integrated OCT-US probe reported. Fast data
      acquisition and processing was implemented for real-time imaging. In vitro OCT
      and US images of human coronary artery with pathology, as well as in vivo images
      of normal rabbit abdominal aorta, were obtained using the integrated OCT-US probe
      to demonstrate its capability.

PMID- 21721800
TI  - High-speed 1310 nm-band spectral domain optical coherence tomography at 184,000
      lines per second.
AB  - We propose a useful method to boost the imaging speed for spectral domain optical
      coherence tomography (SDOCT) by multiplying a number of high-speed spectrometers
      used in the system with selective precise control of data-recording and data
      reading phases for spectral cameras employed in each spectrometer. To demonstrate
      the proposed method, we use two spectrometers built in a 1310 nm-band SDOCT
      system, each equipped with a high-speed InGaAs line-scan camera capable of 92-kHz
      line-scan rate, to achieve an unprecedented imaging speed at 184,000 lines/s. We
      validate the multiplied imaging speed by measuring Doppler-induced phase shift in
      the spectrograms using a flow phantom.

PMID- 21721801
TI  - Rhodamine 800 as a near-infrared fluorescent deposition flow tracer in rodent
      hearts.
AB  - We investigated the use of a near-infrared (NIR) fluorescent dye, Rhodamine 800
      (Rhod800, lambda(exc) = 693 nm, lambda(em) > 720 nm) as a flow-dependent
      molecular tracer for NIR spectroscopy and high-resolution cardiac imaging.
      Rhod800 accumulates in isolated mitochondria in proportion to the mitochondrial
      membrane potential (DeltaPsi). However, in the intact myocardium, Rhod800 binding
      is DeltaPsi-independent. Rat hearts were perfused in a Langendorff mode with
      Krebs-Henseleit buffer containing 45-nM Rhod800 at normal (100%), increased
      (150%), or reduced (50%) baseline coronary flow (CF) per gram, for 30 to 60 min.
      In a different group of hearts, the left anterior descending artery (LAD) was
      occluded prior to Rhod800 infusion to create a flow deficit area. Rhod800
      deposition was analyzed by: 1. absorbance spectroscopy kinetics in the Rhod800
      perfused hearts, 2. Rhod800 absorbance and fluorescence imaging in the short-axis
      heart slices, and 3. dynamic epicardial/subepicardial fluorescence imaging of
      Rhod800 in KCl-arrested hearts, with a spatial resolution of ~ 200 MUm. Rhod800
      deposition was proportional to the perfusate volume (CF and perfusion time) and
      there was no Rhod800 loss during the washout period. In the LAD-ligated hearts,
      Rhod800 fluorescence was missing from the no-flow, LAD-dependent endocardial and
      epicardial/subepicardial area. We concluded that Rhod800 can be used as a
      deposition flow tracer for dynamic cardiac imaging.

PMID- 21721802
TI  - Remote positioning optical breast magnetic resonance coil for slice-selection
      during image-guided near-infrared spectroscopy of breast cancer.
AB  - The design and testing of a pneumatic optical positioning interface produced with
      the goal of improving fiber positioning in magnetic resonance (MR)-guided diffuse
      spectral imaging of breast cancer is presented. The system was created for
      vertical positioning of optical fibers inside the MR bore during a patient exam
      to target suspicious lesions with MR scans for reference and collect multiple
      planes of optical data. The interface includes new fiber plates for mechanical
      and optical coupling to the breast, and was tested in phantoms and human imaging.
      Reconstructions with data taken in the new interface show acceptable linearity
      over different absorber concentrations (residual norm = 0.067), and exhibit good
      contrast recovery at different imaging planes, which is consistent with previous
      work. An example of human breast imaging through the new interface is shown and a
      discussion of how it compares to other patient interfaces for breast imaging is
      presented. Design goals of increasing the available degrees of freedom for fiber
      positioning while maintaining good patient-fiber contact and comfort were
      accomplished. This interface allows improved volumetric imaging with interactive
      and accurate slice selection to quantify targeted suspicious lesions.

PMID- 21721803
TI  - Drug quantification in turbid media by fluorescence imaging combined with light
      absorption correction using white Monte Carlo simulations.
AB  - Accurate quantification of photosensitizers is in many cases a critical issue in
      photodynamic therapy. As a noninvasive and sensitive tool, fluorescence imaging
      has attracted particular interest for quantification in pre-clinical research.
      However, due to the absorption of excitation and emission light by turbid media,
      such as biological tissue, the detected fluorescence signal does not have a
      simple and unique dependence on the fluorophore concentration for different
      tissues, but depends in a complex way on other parameters as well. For this
      reason, little has been done on drug quantification in vivo by the fluorescence
      imaging technique. In this paper we present a novel approach to compensate for
      the light absorption in homogeneous turbid media both for the excitation and
      emission light, utilizing time-resolved fluorescence white Monte Carlo
      simulations combined with the Beer-Lambert law. This method shows that the
      corrected fluorescence intensity is almost proportional to the absolute
      fluorophore concentration. The results on controllable tissue phantoms and murine
      tissues are presented and show good correlations between the evaluated
      fluorescence intensities after the light-absorption correction and absolute
      fluorophore concentrations. These results suggest that the technique potentially
      provides the means to quantify the fluorophore concentration from fluorescence
      images.

PMID- 21721804
TI  - Cyanine dyes as contrast agents for near-infrared imaging in vivo: acute
      tolerance, pharmacokinetics, and fluorescence imaging.
AB  - We compare pharmacokinetic, tolerance, and imaging properties of two near-IR
      contrast agents, indocyanine green (ICG) and 1,1(')-bis-(4-sulfobutyl)
      indotricarbocyanine-5,5(')-dicarboxylic acid diglucamide monosodium salt (SIDAG).
      ICG is a clinically approved imaging agent, and its derivative SIDAG is a more
      hydrophilic counterpart that has recently shown promising imaging properties in
      preclinical studies. The rather lipophilic ICG has a very short plasma half-life,
      thus limiting the time available to image body regions during its vascular
      circulation (e.g., the breast in optical mammography where scanning over several
      minutes is required). In order to change the physicochemical properties of the
      indotricarbocyanine dye backbone, several derivatives were synthesized with
      increasing hydrophilicity. The most hydrophilic dye SIDAG is selected for further
      biological characterization. The acute tolerance of SIDAG in mice is increased up
      to 60-fold compared to ICG. Contrary to ICG, the pharmacokinetic properties of
      SIDAG are shifted toward renal elimination, caused by the high hydrophilicity of
      the molecule. N-Nitrosomethylurea (NMU)-induced rat breast carcinomas are clearly
      demarcated, both immediately and 24 h after intravenous administration of SIDAG,
      whereas ICG shows a weak tumor contrast under the same conditions. Our findings
      demonstrate that SIDAG is a high potential contrast agent for optical imaging,
      which could increase the sensitivity for detection of inflamed regions and
      tumors.

PMID- 21721805
TI  - Chemical changes demonstrated in cartilage by synchrotron infrared
      microspectroscopy in an antibody-induced murine model of rheumatoid arthritis.
AB  - Collagen antibody-induced arthritis develops in mice following passive transfer
      of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to
      effects of proinflammatory immune complexes, but transferred mAbs may react
      directly and damagingly with CII. To determine whether such mAbs cause cartilage
      damage in vivo in the absence of inflammation, mice lacking complement factor 5
      that do not develop joint inflammation were injected intravenously with two
      arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3,
      decalcified, paraffin embedded, and 5-MUm sections were examined using standard
      histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM).
      None of the mice injected with mAb showed visual or histological evidence of
      inflammation but there were histological changes in the articular cartilage
      including loss of proteoglycan and altered chondrocyte morphology. Findings using
      FTIRM at high lateral resolution revealed loss of collagen and the appearance of
      a new peak at 1635 cm(-1) at the surface of the cartilage interpreted as cellular
      activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining
      chemical changes in diseased cartilage at the microscopic level and establish
      that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence
      of inflammation.

PMID- 21721806
TI  - Comparison on different insects' wing displacements using high speed digital
      holographic interferometry.
AB  - In-flight insect wing motion behavior depends on a wide variety of conditions.
      They have a complex structural system and what seems to be a rather complicated
      motion. Researchers in many fields have endeavoured to study and reproduce these
      wing movements with the aim to apply the gained knowledge in their fields and for
      the benefit of avionic technological improvements and insect migration studies,
      among many other themes. The study of in-flight insect wing motion and its
      measurement is a relevant issue to understand and reproduce its functionality.
      Being capable of measuring the wing flapping using optical noninvasive methods
      adds scientific and technological value to the fundamental research in the area.
      Four different types of butterflies found widely in Mexico's forests are used to
      compare their wing flapping mechanisms. An out-of-plane digital holographic
      interferometry system is used to detect and measure its wingmicro deformations.
      Displacement changes from in vivo flapping wings are registered with a CMOS high
      speed camera yielding full field of view images depicting these insects' wing
      motion. The results have a resolution in the scale of hundreds of nanometers over
      the entire wing surface.

PMID- 21721807
TI  - Investigation of formation and interrelations of polarization singular structure
      and Mueller-matrix images of biological tissues and diagnostics of their cancer
      changes.
AB  - We investigate the processes of laser radiation transformation by biological
      crystal networks using the singular optics techniques. The obtained results show
      a distinct correlation between the points of "characteristic" values of
      coordinate distributions of Mueller matrix (M(ik) = 0, +/- 1) elements and
      polarization singularities (L- and C-points) in laser images of biological
      crystal networks with the following possibility of Mueller-matrix selection of
      polarization singularity. The technique of Mueller-matrix singular diagnostics of
      pathological changes in a woman's reproductive sphere tissue (myometrium) is
      proposed.

PMID- 21721808
TI  - Ratiometric spectral imaging for fast tumor detection and chemotherapy monitoring
      in vivo.
AB  - We report a novel in vivo spectral imaging approach to cancer detection and
      chemotherapy assessment. We describe and characterize a ratiometric spectral
      imaging and analysis method and evaluate its performance for tumor detection and
      delineation by quantitatively monitoring the specific accumulation of targeted
      gallium corrole (HerGa) into HER2-positive (HER2 +) breast tumors. HerGa temporal
      accumulation in nude mice bearing HER2 + breast tumors was monitored
      comparatively by a. this new ratiometric imaging and analysis method; b.
      established (reflectance and fluorescence) spectral imaging; c. more commonly
      used fluorescence intensity imaging. We also tested the feasibility of HerGa
      imaging in vivo using the ratiometric spectral imaging method for tumor detection
      and delineation. Our results show that the new method not only provides better
      quantitative information than typical spectral imaging, but also better
      specificity than standard fluorescence intensity imaging, thus allowing enhanced
      in vivo outlining of tumors and dynamic, quantitative monitoring of targeted
      chemotherapy agent accumulation into them.

PMID- 21721809
TI  - Image processing and classification algorithm for yeast cell morphology in a
      microfluidic chip.
AB  - The study of yeast cell morphology requires consistent identification of cell
      cycle phases based on cell bud size. A computer-based image processing algorithm
      is designed to automatically classify microscopic images of yeast cells in a
      microfluidic channel environment. The images were enhanced to reduce background
      noise, and a robust segmentation algorithm is developed to extract geometrical
      features including compactness, axis ratio, and bud size. The features are then
      used for classification, and the accuracy of various machine-learning classifiers
      is compared. The linear support vector machine, distance-based classification,
      and k-nearest-neighbor algorithm were the classifiers used in this experiment.
      The performance of the system under various illumination and focusing conditions
      were also tested. The results suggest it is possible to automatically classify
      yeast cells based on their morphological characteristics with noisy and low
      contrast images.

PMID- 21721810
TI  - Imaging tumor hypoxia by near-infrared fluorescence tomography.
AB  - We have developed a novel nitroimidazole indocyanine dye conjugate for tumor
      targeted hypoxia fluorescence tomography. The hypoxia probe has been evaluated in
      vitro using tumor cell lines and in vivo with tumor targeting in mice. The in
      vitro cell studies were performed to assess fluorescence labeling differences
      between hypoxia and normoxia conditions. When treated with the hypoxia probe, a
      fluorescence emission ratio of 2.5-fold was found between the cells incubated
      under hypoxia compared to the cells in normoxia condition. Hypoxia specificity
      was also confirmed by comparing the cells treated with indocyanine dye alone. In
      vivo tumor targeting in mice showed that the fluorescence signals measured at the
      tumor site were twice those at the normal site after 150 min post-injection of
      the hypoxia probe. On the other hand, the fluorescence signals measured after
      injection of indocyanine dye were the same at tumor and normal sites. In vivo
      fluorescence tomography images of mice injected with the hypoxia probe showed
      that the probe remained for more than 5 to 7 h in the tumors, however, the images
      of mice injected with indocyanine only dye confirmed that the unbound dye washed
      out in less than 3 h. These findings are supported with fluorescence images of
      histological sections of tumor samples using a Li-COR scanner and
      immunohistochemistry technique for tumor hypoxia.

PMID- 21721811
TI  - Fractal analysis for classification of breast carcinoma in optical coherence
      tomography.
AB  - The accurate and rapid assessment of tumor margins during breast cancer resection
      using optical coherence tomography (OCT) has the potential to reduce patient
      risk. However, it is difficult to subjectively distinguish cancer from normal
      fibroglandular stromal tissues in OCT images, and an objective measure is needed.
      In this initial study, we investigate the potential of a one-dimensional fractal
      box-counting method for cancer classification in OCT. We computed the fractal
      dimension, a measure of the self-similarity of an object, along the depth axis of
      44 ultrahigh-resolution OCT images of human breast tissues obtained from 4 cancer
      patients. Correlative histology was employed to identify distinct regions of
      adipose, stroma, and cancer in the OCT images. We report that the fractal
      dimension of stroma is significantly higher than that of cancer (P < 10(-5), t
      test). Furthermore, by adjusting the cutoff values of fractal dimension between
      cancer, stroma, and adipose tissues, sensitivities and specificities of either
      82.4% and 88.9%, or 88.2% and 81.5%, are obtained, respectively, for cancer
      classification. The use of fractal analysis with OCT could potentially provide
      automated identification of tumor margins during breast-sparing surgery.

PMID- 21721812
TI  - Feasibility study on bonding quality inspection of microfluidic devices by
      optical coherence tomography.
AB  - This paper reports the feasibility of optical coherence tomography (OCT)
      technology for inspection of bonding quality of microfluidic devices in
      manufacturing environments. A compact optical-fiber-based OCT is developed and
      its measurement performance is characterized. A series of microfluidic devices
      respectively bonded by adhesive tape, thermal method, and oxygen plasma, are
      inspected. The defects of geometry deformation and sealing completeness are
      emphasized during measurements. Based on the inspection results, some discoveries
      related to the production of microfluidic devices are discussed.

PMID- 21721813
TI  - Red-luminescent europium (III) doped silica nanoshells: synthesis,
      characterization, and their interaction with HeLa cells.
AB  - A simple method to fabricate Eu(3+) doped silica nanoshells particles with 100
      and 200 nm diameters is reported. Amino polystyrene beads were used as templates,
      and an 8 to 10 nm thick silica gel coating was formed by the sol-gel reaction.
      After removing the template by calcination, porous dehydrated silica gel
      nanoshells of uniform size were obtained. The Eu(3+) doped silica nanoshells
      exhibited a red emission at 615 nm on UV excitation. The porous structure of the
      silica shell wall was characterized by transmission electron microscopy
      measurements, while particle size and zeta potentials of the particles suspended
      in aqueous solution were characterized by dynamic light scattering. Two-photon
      microscopy was used to image the nanoshells after assimilation by HeLa cancer
      cells.

PMID- 21721814
TI  - Custom-made modification of a commercial confocal microscope to photolyze caged
      compounds using the conventional illumination module and its application to the
      observation of Inositol 1,4,5-trisphosphate-mediated calcium signals.
AB  - The flash photolysis of "caged" compounds is a powerful experimental technique
      for producing rapid changes in concentrations of bioactive signaling molecules.
      These caged compounds are inactive and become active when illuminated with
      ultraviolet light. This paper describes an inexpensive adaptation of an Olympus
      confocal microscope that uses as source of ultraviolet light the mercury lamp
      that comes with the microscope for conventional fluorescence microscopy. The
      ultraviolet illumination from the lamp (350 - 400 nm) enters through an optical
      fiber that is coupled to a nonconventional port of the microscope. The
      modification allows to perform the photolysis of caged compounds over wide areas
      (~ 200 MUm) and obtain confocal fluorescence images simultaneously. By
      controlling the ultraviolet illumination exposure time and intensity it is
      possible to regulate the amount of photolyzed compounds. In the paper we
      characterize the properties of the system and show its capabilities with
      experiments done in aqueous solution and in Xenopus Laevis oocytes. The latter
      demonstrate its applicability for the study of Inositol 1,4,5-trisphosphate
      mediated intracellular calcium signals.

PMID- 21721815
TI  - Spectrally resolving and scattering-compensated x-ray luminescence/fluorescence
      computed tomography.
AB  - The nanophosphors, or other similar materials, emit near-infrared (NIR) light
      upon x-ray excitation. They were designed as optical probes for in vivo
      visualization and analysis of molecular and cellular targets, pathways, and
      responses. Based on the previous work on x-ray fluorescence computed tomography
      (XFCT) and x-ray luminescence computed tomography (XLCT), here we propose a
      spectrally-resolving and scattering-compensated x-ray luminescence/fluorescence
      computed tomography (SXLCT or SXFCT) approach to quantify a spatial distribution
      of nanophosphors (other similar materials or chemical elements) within a
      biological object. In this paper, the x-ray scattering is taken into account in
      the reconstruction algorithm. The NIR scattering is described in the diffusion
      approximation model. Then, x-ray excitations are applied with different spectra,
      and NIR signals are measured in a spectrally resolving fashion. Finally, a linear
      relationship is established between the nanophosphor distribution and measured
      NIR data using the finite element method and inverted using the compressive
      sensing technique. The numerical simulation results demonstrate the feasibility
      and merits of the proposed approach.

PMID- 21721816
TI  - Development of a catadioptric endoscope objective with forward and side views.
AB  - Autofluorescence endoscopy is a promising functional imaging technique to improve
      screening of pre-cancerous or early cancer lesions in the gastrointestinal (GI)
      tract. Tissue autofluorescence signal is weak compared to white light reflectance
      imaging. Conventional forward-viewing endoscopes are inefficient in the
      collection of light from objects of interest along on the GI luminal wall. A key
      component of a complete autofluorescence endoscope is the light collection
      module. In this paper, we report the design, optimization, prototype development,
      and testing of an endoscope objective that is capable of acquiring simultaneous
      forward and radial views. The radial-view optical design was optimized for a
      balance between image quality and light collection. Modulation transfer function
      (MTF), entrance pupil radius, manufacturability, and field-of-view were
      parameters used in the lens optimization. In comparison with the typical forward
      viewing endoscopes, our nonsequential ray trace simulations suggest the proposed
      radial-view design is more practical in the light collection. To validate the
      proposed simulation methods, a 3:1 scaled-up prototype was fabricated. Contrast
      measurements were taken with the prototype, and then compared with the simulated
      MTF.

PMID- 21721817
TI  - Megahertz streak-mode Fourier domain optical coherence tomography.
AB  - Here we present an ultrahigh-speed Fourier-domain optical coherence tomography
      (OCT) that records the OCT spectrum in streak mode with a high-speed area scan
      camera, which allows higher OCT imaging speed than can be achieved with a line
      scan camera. Unlike parallel OCT techniques that also use area scan cameras, the
      conventional single-mode fiber-based point-scanning mechanism is retained to
      provide a confocal gate that rejects multiply scattered photons from the sample.
      When using a 1000 Hz resonant scanner as the streak scanner, 1,016,000 A-scans
      have been obtained in 1 s. This method's effectiveness has been demonstrated by
      recording in vivo OCT-image sequences of embryonic chick hearts at 1000 frames/s.
      In addition, 2-megahertz OCT data have been obtained with another high speed
      camera.

PMID- 21721818
TI  - Characteristics of subgingival calculus detection by multiphoton fluorescence
      microscopy.
AB  - Subgingival calculus has been recognized as a major cause of periodontitis, which
      is one of the main chronic infectious diseases of oral cavities and a principal
      cause of tooth loss in humans. Bacteria deposited in subgingival calculus or
      plaque cause gingival inflammation, function deterioration, and then
      periodontitis. However, subgingival calculus within the periodontal pocket is a
      complicated and potentially delicate structure to be detected with current dental
      armamentaria, namely dental x-rays and dental probes. Consequently, complete
      removal of subgingival calculus remains a challenge to periodontal therapies. In
      this study, the detection of subgingival calculus employing a multiphoton
      autofluorescence imaging method was characterized in comparison with a one-photon
      confocal fluorescence imaging technique. Feasibility of such a system was studied
      based on fluorescence response of gingiva, healthy teeth, and calculus with and
      without gingiva covered. The multiphoton fluorescence technology perceived the
      tissue-covered subgingival calculus that cannot be observed by the one-photon
      confocal fluorescence method.

PMID- 21721819
TI  - Design of a handheld optical coherence microscopy endoscope.
AB  - Optical coherence microscopy (OCM) combines coherence gating, high numerical
      aperture optics, and a fiber-core pinhole to provide high axial and lateral
      resolution with relatively large depth of imaging. We present a handheld rigid
      OCM endoscope designed for small animal surgical imaging, with a 6-mm diam tip, 1
      mm scan width, and 1-mm imaging depth. X-Y scanning is performed distally with
      mirrors mounted to micro galvonometer scanners incorporated into the endoscope
      handle. The endoscope optical design consists of scanning doublets, an afocal
      Hopkins relay lens system, a 0.4 numerical aperture water immersion objective,
      and a cover glass. This endoscope can resolve laterally a 1.4-MUm line pair
      feature and has an axial resolution (full width half maximum) of 5.4 MUm. Images
      taken with this endoscope of fresh ex-vivo mouse ovaries show structural
      features, such as corpus luteum, primary follicles, growing follicles, and
      fallopian tubes. This rigid handheld OCM endoscope can be useful for a variety of
      minimally invasive and surgical imaging applications.

PMID- 21721820
TI  - Detection of enzyme activity in orthotopic murine breast cancer by fluorescence
      lifetime imaging using a fluorescence resonance energy transfer-based molecular
      probe.
AB  - Cancer-related enzyme activity can be detected noninvasively using activatable
      fluorescent molecular probes. In contrast to "always-on" fluorescent molecular
      probes, activatable probes are relatively nonfluorescent at the time of
      administration due to intramolecular fluorescence resonance energy transfer
      (FRET). Enzyme-mediated hydrolysis of peptide linkers results in reduced FRET and
      increase of fluorescence yield. Separation of signal from active and inactive
      probe can be difficult with conventional intensity-based fluorescence imaging.
      Fluorescence lifetime (FLT) measurement is an alternative method to detect
      changes in FRET. Thus, we investigate FLT imaging for in vivo detection of FRET
      based molecular probe activation in an orthotopic breast cancer model. Indeed,
      the measured FLT of the enzyme-activatable molecular probe increases from 0.62 ns
      just after injection to 0.78 ns in tumor tissue after 4 h. A significant increase
      in FLT is not observed for an always-on targeted molecular probe with the same
      fluorescent reporter. These results show that FLT contrast is a powerful addition
      to preclinical imaging because it can report molecular activity in vivo due to
      changes in FRET. Fluorescence lifetime imaging exploits unique characteristics of
      fluorescent molecular probes that can be further translated into clinical
      applications, including noninvasive detection of cancer-related enzyme activity.

PMID- 21721821
TI  - In vivo photoacoustic tomography of mouse cerebral edema induced by cold injury.
AB  - For the first time, we have implemented photoacoustic tomography (PAT) to image
      the water content of an edema in vivo. We produced and imaged a cold-induced
      cerebral edema transcranially, then obtained blood vessel and water accumulation
      images at 610 and 975 nm, respectively. We tracked the changes at 12, 24, and 36
      h after the cold injury. The blood volume decreased after the cold injury, and
      the maximum area of edema was observed 24 h after the cold injury. We validated
      PAT of the water content of the edema through magnetic Resonance Imaging and the
      water spectrum from the spectrophotometric measurement.

PMID- 21721822
TI  - Photoacoustic spectroscopy of ovarian normal, benign, and malignant tissues: a
      pilot study.
AB  - Photoacoustic spectra of normal, benign, and malignant ovarian tissues are
      recorded using 325-nm pulsed laser excitation in vitro. A total of 102 (34
      normal, 38 benign, and 30 malignant) spectra are obtained from 22 samples
      belonging to normal, benign, and malignant subjects. Applying multi-algorithm
      approach, comprised of methods such as, principal component analysis (PCA) based
      k-nearest neighbor (k-NN) analysis, artificial neural network (ANN) analysis, and
      support vector machine (SVM) analysis, classification of the data has been
      carried out. For PCA, first the calibration set is formed by pooling 45 spectra,
      15 belonging to each of pathologically certified normal, benign, and malignant
      samples. PCA is then performed on the data matrix, comprised of the six spectral
      features extracted from each of 45 calibration samples, and three principal
      components (PCs) containing maximum diagnostic information are selected. The
      scores of the selected PCs are used to train the k-NN, ANN, and SVM classifiers.
      The ANN used is a classical multilayer feed forward network with back propagation
      algorithm for its training. For k-NN, the Euclidean distance based algorithm is
      used and for SVM, one-versus-rest multiclass kernel-radial basis function is
      used. The performance evaluation of the classification results are obtained by
      calculating statistical parameters like specificity and sensitivity. ANN and k-NN
      techniques showed identical performance with specificity and sensitivity values
      of 100 and 86.76%, whereas SVM had these values at 100 and 80.18%, respectively.
      In order to determine the relative diagnostic performance of the techniques,
      receiver operating characteristics analysis is also performed.

PMID- 21721823
TI  - Characterization of individual ultrasound microbubble dynamics with a light
      scattering system.
AB  - Ultrasound microbubbles are contrast agents used for diagnostic ultrasound
      imaging and as carriers for noninvasive payload delivery. Understanding the
      acoustic properties of individual microbubble formulations is important for
      optimizing the ultrasound imaging parameters for improved image contrast and
      efficient payload delivery. We report here a practical and simple optical tool
      for direct real-time characterization of ultrasound contrast microbubble dynamics
      based on light scattering. Fourier transforms of raw linear and nonlinear
      acoustic oscillations, and microbubble cavitations are directly recorded.
      Further, the power of this tool is demonstrated by comparing clinically relevant
      microbubble cycle-to-cycle dynamics and their corresponding Fourier transforms.

PMID- 21721824
TI  - Label-free and noninvasive optical detection of the distribution of nanometer
      size mitochondria in single cells.
AB  - A microfluidic flow cytometric technique capable of obtaining information on
      nanometer-sized organelles in single cells in a label-free, noninvasive optical
      manner was developed. Experimental two-dimensional (2D) light scattering patterns
      from malignant lymphoid cells (Jurkat cell line) and normal hematopoietic stem
      cells (cord blood CD34+ cells) were compared with those obtained from finite
      difference time-domain simulations. In the simulations, we assumed that the
      mitochondria were randomly distributed throughout a Jurkat cell, and aggregated
      in a CD34+ cell. Comparison of the experimental and simulated light scattering
      patterns led us to conclude that distinction from these two types of cells may be
      due to different mitochondrial distributions. This observation was confirmed by
      conventional confocal fluorescence microscopy. A method for potential cell
      discrimination was developed based on analysis of the 2D light scattering
      patterns. Potential clinical applications using mitochondria as intrinsic
      biological markers in single cells were discussed in terms of normal cells (CD34+
      cell and lymphocytes) versus malignant cells (THP-1 and Jurkat cell lines).

PMID- 21721825
TI  - Mitochondrial function and tissue vitality: bench-to-bedside real-time optical
      monitoring system.
AB  - BACKGROUND: The involvement of mitochondria in pathological states, such as
      neurodegenerative diseases, sepsis, stroke, and cancer, are well documented.
      Monitoring of nicotinamide adenine dinucleotide (NADH) fluorescence in vivo as an
      intracellular oxygen indicator was established in 1950 to 1970 by Britton Chance
      and collaborators. We use a multiparametric monitoring system enabling assessment
      of tissue vitality. In order to use this technology in clinical practice, the
      commercial developed device, the CritiView (CRV), is tested in animal models as
      well as in patients. METHODS AND RESULTS: The new CRV enables the optical
      monitoring of four different parameters, representing the energy balance of
      various tissues in vivo. Mitochondrial NADH is measured by surface
      fluorometry/reflectometry. In addition, tissue microcirculatory blood flow,
      tissue reflectance and oxygenation are measured as well. The device is tested
      both in vitro and in vivo in a small animal model and in preliminary clinical
      trials in patients undergoing vascular or open heart surgery. In patients, the
      monitoring is started immediately after the insertion of a three-way Foley
      catheter (urine collection) to the patient and is stopped when the patient is
      discharged from the operating room. The results show that monitoring the urethral
      wall vitality provides information in correlation to the surgical procedure
      performed.

PMID- 21721826
TI  - In vivo diagnosis of colonic precancer and cancer using near-infrared
      autofluorescence spectroscopy and biochemical modeling.
AB  - The aim of this study is to evaluate the biochemical foundation and clinical
      capability of an image-guided near-infrared (NIR) autofluorescence (AF)
      spectroscopy technique for in vivo diagnosis of colonic malignancies during
      clinical colonoscopy. A novel endoscopic fiber-optic AF system was utilized for
      in vivo NIR AF measurements at 785 nm excitation. A total of 263 in vivo NIR AF
      spectra of colonic tissues were measured from 100 patients, in which 164 spectra
      were from benign tissue (116 normal and 48 hyperplastic polyps), 34 spectra were
      from precancer (adenomatous polyps), and 65 spectra were from cancer. The non
      negativity constrained least squares minimization biochemical modeling was
      explored to estimate the biochemical compositions of colonic tissue using nine
      basis reference spectra from the representative biochemicals (i.e., collagen I,
      elastin, beta-nicotinamide adenine dinucleotide, flavin adenine dinucleotide, L
      tryptophan, hematoporphyrin, 4-pyridoxic acid, pyridoxal 5'-phosphate, and water)
      associated with structural or cellular metabolic progression in colonic precancer
      and cancer. High-quality in vivo NIR AF spectra in the spectral range of 810 to
      1000 nm were acquired from colonic benign, precancerous, and cancerous mucosa
      under white-light reflectance endoscopic imaging guidance. Partial least squares
      discriminant analysis, together with the leave-one tissue site-out, cross
      validation on in vivo NIR AF spectra yields diagnostic sensitivities of 85.4%,
      76.5%, and 84.6%, and specificities of 89.9%, 93.4%, and 91.4%, respectively, for
      classification of benign, precancer, and cancer in the colon. This work
      demonstrates that image-guided NIR AF spectroscopy in conjunction with
      biochemical modeling has promising potential for improving in vivo detection and
      diagnosis of colonic precancer and cancer during clinical colonoscopic screening.

PMID- 21721827
TI  - Modeling of reflectometric and ellipsometric spectra from the skin in the
      terahertz and submillimeter waves region.
AB  - The human skin is modeled as a stack of homogeneous layers in the terahertz and
      submillimeter waves regions with some anisotropy due to the helical sweat glands
      and other elongated entities. A dielectric model for the skin is presented, valid
      for a wider frequency range (up to the terahertz region) taking into account the
      dispersive nature of the effective conductivity. Polarized reflectivity and
      generalized ellipsometric parameters are calculated versus angle and wavelength.
      Recent studies have claimed that the helical sweat ducts act as an array of low-Q
      helical antennae and are dominant in shaping the spectral response in the sub
      terahertz region. We found that water absorption, dispersion and multiple
      interference effects play the major role in shaping the spectrum without the need
      for the assumption of the sweat ducts acting as low-Q helical antennae. High
      sensitivities to the water content are found particularly in the ellipsometric
      parameters at large incidence angles. Hence a new methodology is proposed to
      detect skin cancer using variable angle ellipsometry or polarized reflectometry.
      The parameter found with the highest sensitivity to water content is cos
      Delta(pp) with Delta(pp) being the phase of the on-diagonal reflection matrix
      ratio between p-to-p polarization.

PMID- 21721828
TI  - Measurement of optical scattering properties with low-coherence enhanced
      backscattering spectroscopy.
AB  - Low-coherence enhanced backscattering (LEBS) is a depth selective technique that
      allows noninvasive characterization of turbid media such as biological tissue.
      LEBS provides a spectral measurement of the tissue reflectance distribution as a
      function of distance between incident and reflected ray pairs through the use of
      partial spatial coherence broadband illumination. We present LEBS as a new depth
      selective technique to measure optical properties of tissue in situ. Because LEBS
      enables measurements of reflectance due to initial scattering events, LEBS is
      sensitive to the shape of the phase function in addition to the reduced
      scattering coefficient (MU(s) (*)). We introduce a simulation of LEBS that
      implements a two parameter phase function based on the Whittle-Matern refractive
      index correlation function model. We show that the LEBS enhancement factor (E)
      primarily depends on MU(s) (*), the normalized spectral dependence of E (S(n))
      depends on one of the two parameters of the phase function that also defines the
      functional type of the refractive index correlation function (m), and the LEBS
      peak width depends on both the anisotropy factor (g) and m. Three inverse models
      for calculating these optical properties are described and the calculations are
      validated with an experimental measurement from a tissue phantom.

PMID- 21721829
TI  - Is resting-state functional connectivity revealed by functional near-infrared
      spectroscopy test-retest reliable?
AB  - Recently, resting-state functional near-infrared spectroscopy (rs-fNIRS) research
      has experienced tremendous progress. Resting-state functional connectivity (RSFC)
      has been adopted as a pivotal biomarker in rs-fNIRS studies. However, it is yet
      to be clear if the RSFC derived from rs-fNIRS is reliable. This concern impedes
      extensive utilization of rs-fNIRS. We systematically address the issue of
      reliability. Sixteen subjects participate in two rs-fNIRS sessions held one week
      apart. RSFC in sensorimotor system is calculated using the seed-correlation
      approach. Then, test-retest reliability is evaluated at three different scales
      (map-, cluster-, and channelwise) for individual- and group-level RSFC derived
      from different types of fNIRS signals [oxygenated (HbO), deoxygenated (HbR), and
      total hemoglobin (HbT)]. The results show that, for HbO signals, individual-level
      RSFC generally has good-to-excellent map-/clusterwise reliability, while group
      level RSFC has excellent reliability. For HbT signals, the results are similar.
      For HbR signals, the clusterwise reliability is comparable to that for HbO while
      the mapwise reliability is slightly lower (fair to good). Focusing on RSFC at a
      single channel, we report poor channelwise reliability for all three types of
      signals. We hereby propose that fNIRS-derived RSFC is a reliable biomarker if
      interpreted in map- and clusterwise manners. However, channelwise interpretation
      of individual RSFC should proceed with caution.

PMID- 21721830
TI  - Spectral classifier design with ensemble classifiers and misclassification
      rejection: application to elastic-scattering spectroscopy for detection of
      colonic neoplasia.
AB  - Optical spectroscopy has shown potential as a real-time, in vivo, diagnostic tool
      for identifying neoplasia during endoscopy. We present the development of a
      diagnostic algorithm to classify elastic-scattering spectroscopy (ESS) spectra as
      either neoplastic or non-neoplastic. The algorithm is based on pattern
      recognition methods, including ensemble classifiers, in which members of the
      ensemble are trained on different regions of the ESS spectrum, and
      misclassification-rejection, where the algorithm identifies and refrains from
      classifying samples that are at higher risk of being misclassified. These
      "rejected" samples can be reexamined by simply repositioning the probe to obtain
      additional optical readings or ultimately by sending the polyp for
      histopathological assessment, as per standard practice. Prospective validation
      using separate training and testing sets result in a baseline performance of
      sensitivity = .83, specificity = .79, using the standard framework of feature
      extraction (principal component analysis) followed by classification (with linear
      support vector machines). With the developed algorithm, performance improves to
      Se ~ 0.90, Sp ~ 0.90, at a cost of rejecting 20-33% of the samples. These results
      are on par with a panel of expert pathologists. For colonoscopic prevention of
      colorectal cancer, our system could reduce biopsy risk and cost, obviate
      retrieval of non-neoplastic polyps, decrease procedure time, and improve
      assessment of cancer risk.

PMID- 21721831
TI  - Wavelength-resolved measurements of fluorescence lifetime of indocyanine green.
AB  - We study fluorescence lifetime of indocyanine green (ICG) using femtosecond laser
      and sensitive detection based on time-correlated single-photon counting. A time
      resolved multichannel spectral system is constructed and applied for
      determination of the fluorescence lifetime of the ICG in different solvents.
      Emission properties of ICG in water, milk, and 1% intralipid solution are
      investigated. Fluorescence of the fluorophore of different concentrations (in a
      range of 1.7-160 MUM) dissolved in different solutions is excited by femtosecond
      pulses generated with the use of Ti:Sa laser tuned within the range of 740-790
      nm. It is observed that fluorescence lifetime of ICG in water is 0.166 +/- 0.02
      ns and does not depend on excitation and emission wavelengths. We also show that
      for the diffusely scattering solvents (milk and intralipid), the lifetime may
      depend on the dye concentration (especially for large concentrations of ICG).
      This effect should be taken into account when analyzing changes in the mean time
      of arrival of fluorescence photons excited in ICG dissolved in such optically
      turbid media.

PMID- 21721832
TI  - Measuring and predicting eyelid spectral transmittance.
AB  - The purpose of the present study was to objectively quantify the spectral
      transmittance of the eyelid. Reported here are data acquired using a technique
      that was developed to provide practical and accurate measurements of eyelid
      transmittance across the visible portion of the electromagnetic spectrum. The
      empirical data were analyzed in terms of the absorption and scattering
      characteristics of the constituents of skin to develop a method for predicting
      eyelid transmission. Results showed that the eyelid has a much higher optical
      density at short wavelengths than previously published. The mean +/- standard
      deviation (s.d.) optical density of the eyelid from 450 to 650 nm was 2.1 +/- 0.3
      with an optical density range among subjects of approximately 1.0. The study
      results indicate that skin pigmentation is poorly correlated with eyelid
      transmission; eyelid transmission is most affected by wavelength-independent
      macromolecules in the eyelid as well as its overall thickness.

PMID- 21721833
TI  - Near-infrared autofluorescence for the detection of parathyroid glands.
AB  - A major challenge in endocrine surgery is the intraoperative detection of
      parathyroid glands during both thyroidectomies and parathyroidectomies. Current
      localization techniques such as ultrasound and sestamibi scan are mostly
      preoperative and rely on an abnormal parathyroid for its detection. In this
      paper, we present near-infrared (NIR) autofluorescence as a nonintrusive, real
      time, automated in vivo method for the detection of the parathyroid gland. A
      pilot in vivo study was conducted to assess the ability of NIR fluorescence to
      identify parathyroid glands during thyroid and parathyroidectomies. Fluorescence
      measurements at 785 nm excitation were obtained intra-operatively from the
      different tissues exposed in the neck region in 21 patients undergoing endocrine
      surgery. The fluorescence intensity of the parathyroid gland was found to be
      consistently greater than that of the thyroid and all other tissues in the neck
      of all patients. In particular, parathyroid fluorescence was two to eleven times
      higher than that of the thyroid tissues with peak fluorescence occurring at 820
      to 830 nm. These results indicate that NIR fluorescence has the potential to be
      an excellent optical tool to locate parathyroid tissue during surgery.

PMID- 21721834
TI  - Reduced nicotinamide adenine dinucleotide fluorescence lifetime detected
      poly(adenosine-5'-diphosphate-ribose) polymerase-1-mediated cell death and
      therapeutic effect of pyruvate.
AB  - Noninvasive detection of cell death has the potential for definitive diagnosis
      and monitoring treatment outcomes in real time. Reduced nicotinamide adenine
      dinucleotide (NADH) fluorescence intensity has long been used as a noninvasive
      optical probe of metabolic states. NADH fluorescence lifetime has recently been
      studied for its potential as an alternative optical probe of cellular metabolic
      states and cell death. In this study, we investigated the potential using NADH
      fluorescence intensity and/or lifetime to detect poly(adenosine-5'-diphosphate
      ribose) polymerase-1 (PARP-1)-mediated cell death in HeLa cells. We also examined
      if NADH signals respond to treatment by pyruvate. The mechanism of PARP-1
      mediated cell death has been well studied that extensive PARP-1 activation leads
      to cytosolic nicotinamide adenine dinucleotide depletion resulting in glycolytic
      inhibition, mitochondrial failure, and death. Pyruvate could restore electron
      transport chain to prevent energy failure and death. Our results show that NADH
      fluorescence lifetime, not intensity, responded to PARP-1-mediated cell death and
      the rescue effect of pyruvate. This lifetime change of NADH fluorescence happened
      before the collapse of mitochondrial membrane potential and mitochondrial
      uncoupling. Together with our previous findings in staurosporine-induced cell
      death, we suggest that NADH fluorescence lifetime increase during cell death is
      mainly due to increased protein-protein interactions but not the intracellular
      NADH content.

PMID- 21721837
TI  - Carbon nanotubes and pleural damage: perspectives of nanosafety in the light of
      asbestos experience.
AB  - Carbon nanotubes are molecular-scale one-dimensional manufactured materials which
      display several potential applications in engineering and materials science.
      Burgeoning evidence demonstrates that carbon nanotubes and asbestos share
      comparable physical properties. Therefore carbon nanotubes might display toxic
      effects and the extent of the toxicity is more specifically directed to lung and
      pleura. These effects are related to properties of carbon nanotubes, such as
      their structure, length, aspects ratio, surface area, degree of aggregation,
      extent of oxidation, bound functional group, method of manufacturing,
      concentration and dose. At the present there is no global agreement about the
      risk of carbon nanotubes on human health and in particular on their
      transformation capacity. Safety concerns regarding carbon nanotubes can be
      ameliorated. In this context, it is important to put the known hazards of carbon
      nanotubes into perspective. Here is presented an overview about toxicity issues
      in the application of carbon nanotubes to biological systems, taking into
      consideration the already known asbestos-induced mechanisms of biological
      damages.

PMID- 21721838
TI  - Paclitaxel delivery from cobalt-chromium alloy surfaces using self-assembled
      monolayers.
AB  - Polymer-based platforms in drug-eluting stents (DESs) can cause adverse reactions
      in patients. Hence, the development of a polymer-free drug delivery platform may
      reduce adverse reactions to DES. In this study, the use of a polymer-free
      platform, self-assembled monolayers (SAMs), is explored for delivering an
      antiproliferative drug [paclitaxel (PAT)] from a stent material [cobalt-chromium
      ((Co-Cr) alloy]. Initially, carboxylic acid terminated phosphonic acid SAMs were
      coated on Co-Cr alloy. Two different doses (25 and 100 MUg/cm2) of PAT were
      coated on SAM coated Co-Cr surfaces using a microdrop deposition method. Also,
      control experiments were carried out to coat PAT directly on Co-Cr surfaces with
      no SAM modification. The PAT coated specimens were characterized using the
      Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy
      (SEM), and atomic force microscopy (AFM). FTIR spectra showed the successful
      deposition of PAT on SAM coated and control-Co-Cr surfaces. SEM images showed
      islands of high density PAT crystals on SAM coated surfaces, while low density
      PAT crystals were observed on control-Co-Cr alloy. AFM images showed molecular
      distribution of PAT on SAM coated as well as control-Co-Cr alloy surfaces. In
      vitro drug release studies showed that PAT was released from SAM coated Co-Cr
      surfaces in a biphasic manner (an initial burst release in first 7 days was
      followed by a slow release for up to 35 days), while the PAT was burst released
      from control-Co-Cr surfaces within 1-3 days. Thus, this study demonstrated the
      use of SAMs for delivering PAT from Co-Cr alloy surfaces for potential use in
      drug-eluting stents.

PMID- 21721840
TI  - Biomimetic assembly of polyelectrolyte multilayers containing phosvitin monitored
      with reflectometric interference spectroscopy.
AB  - Coatings of biomaterials or implants that facilitate biomineralization possess a
      great potential for applications focused to the replacement, augmentation, and
      regeneration of bone tissue. Biomimetic approaches utilize biomolecules for
      either templating or supporting the crystallization process. One of these
      promising biomolecules is phosvitin (PV), an egg yolk protein known to transport
      and store inorganic phosphates and calcium ions. The incorporation of PV into
      polyelectrolyte multilayers is favorable due to PVs high degree of
      phosphorylation and thus a high acidity. Utilizing the reflectometric
      interference spectroscopy, the adsorption kinetics of this novel polyelectrolyte
      system composed of poly-L-lysine and the heavily phosphorylated phosvitin were
      monitored. The results demonstrate an unexpected nonregular growth regime called
      overshoot. Effective measures of shifting this irregular polyelectrolyte
      adsorption process back to a regular multilayer growth regime are reported in
      this paper.

PMID- 21721839
TI  - Modulation of fibroblast inflammatory response by surface modification of a
      perfluorinated ionomer.
AB  - An ideal surface for implantable glucose sensors would be able to evade the
      events leading to chronic inflammation and fibrosis, thereby extending its
      utility in an in vivo environment. NafionTM, a perfluorinated ionomer, is the
      membrane material preferred for in situ glucose sensors. Unfortunately, the
      surface properties of NafionTM promote random protein adsorption and eventual
      foreign body encapsulation, thus leading to loss of glucose signal over time.
      Details of the techniques to render NafionTM nonprotein fouling are given in a
      previous article [T. I. Valdes et al., Biomaterials 29, 1356 (2008)]. Once random
      protein adsorption is prevented, a biologically active peptide can be covalently
      bonded to the treated NafionTM to induce cellular adhesion. Cellular responses to
      these novel decorated NafionTM surfaces are detailed here, including cell
      viability, cell spreading, and type I collagen synthesis. Normal human dermal
      fibroblasts (NHDFs) were cultured on control and modified NafionTM surfaces.
      Findings indicate that NafionTM modified with 10% 2-hydroxyethyl methacrylate and
      90% tetraglyme created a nonfouling surface that was subsequently decorated with
      the YRGDS peptide. NHDFs were shown to have exhibited decreased type I collagen
      production in comparison to NHDF cells on unmodified NafionTM surfaces. Here, the
      authors report evidence that proves that optimizing conditions to prevent protein
      adsorption and enhance cellular adhesion may eliminate fibrous encapsulation of
      an implant.

PMID- 21721841
TI  - Multitechnique study on a recombinantly produced Bacillus halodurans laccase and
      an S-layer/laccase fusion protein.
AB  - Methods for organizing functional materials at the nanometer scale are essential
      for the development of novel fabrication techniques. One of the most relevant
      areas of research in nanobiotechnology concerns technological utilization of self
      assembly systems, wherein molecules spontaneously associate into reproducible
      supramolecular structures. For this purpose, the laccase of Bacillus halodurans C
      125 was immobilized on the S-layer lattice formed by SbpA of Lysinibacillus
      sphaericus CCM 2177 either by (i) covalent linkage of the enzyme to the natural
      protein self-assembly system or (ii) by construction of a fusion protein
      comprising the S-layer protein and the laccase. The laccase and the S-layer
      fusion protein were produced heterologously in Escherichia coli. After isolation
      and purification, the properties of the proteins, as well as the specific
      activity of the enzyme moiety, were investigated. Interestingly, the S-layer part
      confers a much higher solubility on the laccase as observed for the sole enzyme.
      Comparative spectrophotometric measurements of the enzyme activity revealed
      similar but significantly higher values for rLac and rSbpA/Lac in solution
      compared to the immobilized state. However, rLac covalently linked to the SbpA
      monolayer yielded a four to five time higher enzymatic activity than rSbpA/Lac
      immobilized on a solid support. Combined quartz crystal microbalance with
      dissipation monitoring (QCM-D) and electrochemical measurements (performed in an
      electrochemical QCM-D cell) revealed that rLac immobilized on the SbpA lattice
      had an approximately twofold higher enzymatic activity compared to that obtained
      with the fusion protein.

PMID- 21721842
TI  - Phase separation of phospholipid multilayers incorporated with cell penetrating
      peptides.
AB  - We used X-ray reflectivity to investigate the structures of phospholipid
      multilayers with transcription-activating-factor-derived peptide (TDP) as a
      function of the membrane charge density. Mixed phospholipid multilayers of 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl -sn-glycero-3
      phosphoserine (DPPS) with different mixing ratios (C:S) were used to elucidate
      the various charge densities in a plasma membrane. We fixed the peptide/lipid
      molar ratio (P/L) and varied the DPPC/DPPS molar ratio in the mixed multilayer.
      In the pure DPPC multilayer, the incorporation of TDP had nearly no effect on the
      bilayer thickness of the mixed lipid multilayer. However, in the mixed DPPC/DPPS
      multilayer, the incorporation of TDP decreased the bilayer thickness, suggesting
      that the TDP peptide had a stronger interaction with DPPS than with DPPC and
      caused disorder in the lamellar structure. Combining this with the refined X-ray
      reflectivity (XR) data, we concluded that the TDP existed more in the headgroup
      region of the TDP-induced segregated DPPS in the mixed multilayer and caused
      significant membrane thinning.

PMID- 21721843
TI  - Elastic moduli of living epithelial pancreatic cancer cells and their
      skeletonized keratin intermediate filament network.
AB  - In simple epithelia, such as living epithelial pancreatic cancer cells (Panc-1),
      unusual amounts of keratin filaments can be found, which makes these cells an
      ideal model system to study the role of keratin for cell mechanical properties.
      In this work, the elastic moduli of Panc-1 cells and their extracted in-situ
      subcellular keratin intermediate filament network are determined and compared
      with each other. For this, the living adherent cells and their extracted keratin
      network were probed with local quasistatic indentation testing during large
      deformations using the Atomic Force Microscope (AFM). We determined the elastic
      modulus of the skeletonized but structurally intact keratin network to be in the
      order of 10 Pa, while the living cell elastic modulus ranged from 100 to 500 Pa.
      By removing microfilaments, microtubules, membranes and soluble cytoplasmic
      components during keratin network extraction, we excluded effects caused by
      crosslinking with other filamentous fibers and from the viscosity of the
      cytoplasm. Thus, the determined elastic modulus equals the actual elastic modulus
      inherent to such a keratin filamentous network. In our assessment of the
      effective mechanical contribution of the architecturally intact, skeletonized
      keratin network to living cell mechanics, we come to the conclusion that it plays
      only a very limited role. Evidently, the quantitative dominance of keratin in
      these cells does not reflect a strong influence on determining the cell's elastic
      modulus. Instead, keratin like other filamentous structures in the cell's
      scaffolding, e.g., F-actin and microtubuli, is one part of a greater whole.

PMID- 21721844
TI  - Participation of people with acquired brain injury: Insiders perspectives.
AB  - INTRODUCTION: Participation is important in rehabilitation of people with
      acquired brain injury (ABI). Studies have shown that their participation is
      problematic. It is, however, unknown how they experience their participation and
      what influences their participation. This study aims to answer the question how
      people with ABI experience participation and which environmental and personal
      factors may influence participation, as perceived by people with ABI. METHODS: A
      qualitative methodology was conducted by a team consisting of researchers, people
      with ABI and a mother of a daughter with ABI. Interviews and focus groups were
      held and followed by a working group in order to develop actions for improvement.
      RESULTS AND CONCLUSION: People with ABI contend that it is not the degree of
      participation that matters, but the quality of participation. They describe
      meaningful participation in terms of taking part, giving something and being
      someone. A model was constructed based on the experiences, which includes
      personal and environmental factors that, in interaction, may influence
      participation: participation is influenced by the process of recovery, support
      and treatment, the environment and society and communication and interaction. The
      study resulted in an overview of actions like continual care that may improve the
      participation of people with ABI.

PMID- 21721845
TI  - The contribution of retrospective memory, attention and executive functions to
      the prospective and retrospective components of prospective memory following TBI.
AB  - PRIMARY OBJECTIVE: Despite the prevalence of prospective memory (PM) problems,
      relatively little is known about the processes underlying impairment following
      TBI. This study sought to examine PM performance, using a multiple-task, multiple
      response video-based paradigm in which initial encoding of the cue-action
      associations was ensured (Video-Assessment of Prospective Memory; VAPM). RESEARCH
      DESIGN: VAPM was designed to allow easy identification of reasons for failure
      (i.e. cue detection and/or specific action retrieval). Patients with
      moderate/severe TBI (n = 32) and matched controls (n = 16) also completed
      standardized neuropsychological assessment including evaluation of episodic
      retrospective memory (RM), attention, information processing, executive functions
      and mood. MAIN OUTCOMES AND RESULTS: As a group, those with TBI were impaired on
      PM tasks with 50% failing to complete at least 2/6 required tasks despite near
      perfect performance by controls. Individual profile analyses revealed different
      reasons for impairment, with RM contributing significantly to both the
      prospective and retrospective components. This was supported by correlational
      analyses illustrating a significant relationship between cue detection and RM
      measures, in addition to measures of executive functions and attention.
      CONCLUSIONS: The contribution of RM to both components of PM, along with the
      finding of heterogeneity in performance among participants have important
      implications for theoretical understanding and clinical practice.

PMID- 21721846
TI  - Preparation of amifostine polylactide-co-glycolide microspheres and its
      irradiation protective to mouse through oral administration.
AB  - The objectives of this study were to prepare the amifostine polylactide-co
      glycolide (PLGA) microsphere and investigate its irradiation protective to mouse
      through oral administration. Amifostine-loaded PLGA microsphere was formulated
      using a modified double emulsion-solvent evaporation technique. The microsphere
      particle was spherical with a mean diameter of 2.8 +/- 0.1 MUm. Release data of
      amifostine PLGA microsphere was tested in phosphate-buffered saline at 37 degrees
      C using a dialysis method and its release profiles was biphasic, showing a
      relatively large burst effect (50%) over the first 6 h, followed by a slower
      release phase, which sustained with 80% amifostine released in 48 h and almost
      100% release till 6 days (144 h). A diffusion-controlled release model (Higuchi
      equation, R2 = 0.9725) was obtained for amifostine releasing from PLGA
      microsphere. The radiation experiment was performed by applied cobalt-60 gamma
      radiation source. One hour before gamma-radiation exposure, the mouse was orally
      given free amifostine and PLGA microsphere, respectively. The irradiation
      effects, such as blood cell concentration, superoxidase dismutase (SOD) activity
      and malondialdehyde (MDA) level were monitored. The results indicated that
      amifostine PLGA microsphere was more irradiation protective to mouse than that of
      free amifostine under the same oral administration route.

PMID- 21721847
TI  - The current role of high-dose imatinib in chronic myeloid leukemia patients,
      newly diagnosed or resistant to standard dose.
AB  - INTRODUCTION: The majority of patients affected by chronic myeloid leukemia (CML)
      are expected to obtain a favorable outcome with standard-dose imatinib. However,
      a third of patients do not achieve the desired effect and must be considered
      resistant. One of the early strategies to overcome initial resistance was the use
      of high doses (600 - 800 mg) of imatinib: before the advent of second-generation
      tyrosine kinase inhibitors, some standard-dose-resistant patients gained benefits
      from the use of dose-escalation imatinib. Intensification with higher doses of
      the drug was used in newly diagnosed patients with the aim to improve cytogenetic
      and molecular responses. AREAS COVERED: In this article, the authors review data
      of several trials testing high-dose imatinib after resistance to standard dose.
      Literature about high-dose imatinib used front-line as single treatment or with
      different combinations is also examined. A literature search for relevant studies
      was undertaken mainly in PubMed or through published conference abstracts. The
      aim of this review is to summarize the efficacy and safety of this option either
      as front-line or as a rescue therapy in chronic-phase CML patients and to discuss
      the future role of this treatment modality. EXPERT OPINION: Literature evidence
      supports the fact that high-dose imatinib can induce sustained responses in a
      subset of patients with cytogenetic failure or acquired resistance, but it seems
      less effective in patients with haematological failure or in molecular suboptimal
      responders. In newly diagnosed patients, high-dose imatinib produced increased
      response rates, which in some instances were not significant compared with
      standard dose.

PMID- 21721848
TI  - Conjugated linoleic acid isomers may diminish human macrophages adhesion to
      endothelial surface.
AB  - Dysfunction of endothelial cells and activation of monocytes in the vascular wall
      are important pathogenetic factors of atherosclerosis. Conjugated linoleic acids
      (CLAs) can modulate the function of immune system in humans: reduce the
      concentration of atherogenic lipoproteins, and the intensity of inflammatory
      processes in the plasma. In this paper, we focus on macrophage's surface
      integrins (beta1 integrin CD49d/CD29-(VLA4); Mac-1 as well as endothelial human
      vein endothelial cell (HUVEC) surface adhesins: vascular cell adhesion molecule-1
      (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1)) expression in
      relation to CLA isomer used during cell culture. Both CLA isomers decreased
      expression of VLA-4 and Mac-1 on macrophages compared with control cells
      (cultured with bovine serum albumine (BSA) or oxidized form of low-density
      lipoproteins). cis-9, trans-11 CLA isomer reduced ICAM-1 and VCAM-1 expression on
      the endothelium surface. Strong tendency to reduce of adhesion of macrophages to
      HUVEC in the cells cultured with CLA isomers was observed. The potential role of
      cis-9, trans-11 CLA in the reduction of adhesion of macrophages to the HUVEC--one
      of the important steps in the inflammatory process, can be considerate. These
      mechanisms may contribute to the potent anti-atherosclerotic effects of CLA in
      vivo.

PMID- 21721849
TI  - Cross-sectional associations between physical activity and selected coronary
      heart disease risk factors in young adults. The Cardiovascular Risk in Young
      Finns Study.
AB  - OBJECTIVE: Physical activity (PA) may reduce the risk of coronary heart disease
      (CHD) by inducing beneficial changes in several risk factors. We studied the
      associations between PA and a range of risk markers of CHD in young adults.
      METHODS AND RESULTS: We measured serum lipoproteins, oxidized LDL, adipokines,
      inflammatory markers, metabolic markers, and arginine metabolites in 2,268
      individuals (age 24-39 y). Participants were asked frequency, duration, and
      intensity of PA in leisure time. In addition, commuting to work was assessed. In
      both sexes, PA was inversely associated with waist circumference (all P <
      0.0001). After controlling for sex, age, and waist circumference, PA was directly
      associated with HDL-cholesterol and apolipoprotein A1, and inversely with heart
      rate, smoking, oxidized LDL, apolipoprotein B, insulin, glucose, C-reactive
      protein, leptin, L-arginine, and phospholipase A2 activity (all P < 0.05).
      CONCLUSION: These population-based data are consistent with the idea that the
      beneficial effects of PA on CHD risk are mediated by favorable influences on
      several risk factors, as judged by independent relations to markers of
      lipoprotein metabolism, glucose metabolism, and inflammation. These associations
      reflect beneficial effects on cardiovascular health in both sexes and may offer
      mechanistic insights for the inverse association between PA and CHD.

PMID- 21721850
TI  - Relevance of air-to-liquid mass ratio effect on final granule properties of an
      Enalapril maleate formulation.
AB  - BACKGROUND: In the production of enalapril maleate tablets, the granulation
      process is the most crucial step. Numerous variables are known to influence the
      fluid bed granulation process and thus the final granule quality. In this study a
      novel descriptor for the nozzle parameter "air-to-liquid mass ratio" is
      presented. Granules manufacturing processes were designed by application of
      statistical experimental design. AIM: The influence of the critical process
      parameter (CPP)--air-to-liquid mass ratio--on pharmaceutic properties of granules
      was studied. Air-to-liquid mass ratio can be considered as important variable
      influencing the droplet size of atomized liquid binder solution.
      RESULTS/CONCLUSION: A significant influence of air-to-liquid mass ratio on
      granule final particle size distribution was found. Increasing air-to-liquid mass
      ratio resulted in increased granules particle size distribution. Decreasing air
      to-liquid mass ratio led to granules with reduced tapped density. Thus, it can be
      concluded that the parameter "air-to-liquid mass ratio" is a critical process
      parameter in the production of enalapril maleate granules.

PMID- 21721851
TI  - Development of an inhalation chamber and a dry powder inhaler device for
      administration of pulmonary medication in animal model.
AB  - CONTEXT: Pulmonary route of administration is becoming more popular for drug
      delivery in pulmonary tract and lungs for local and systemic actions. OBJECTIVE:
      A dry powder inhaler (DPI) for delivery of dry powder and a nose-only inhalation
      chamber for small animals that can be used with nebuliser/DPI were designed.
      MATERIALS AND METHODS: The inhalation chamber was made with a polypropylene
      rectangular box and centrifuge tubes. DPI was made of a polypropylene tube.
      Micronized voriconazole and voriconazole solution were used for DPI and
      nebulizer, respectively, for both in vitro and in vivo studies. RESULTS: In vitro
      drug deposition from nebulizer was found to be 11-26% w/w and that from DPI was
      42 to 57% w/w depending on experimental set up. Uniform deposition across all the
      inhalation ports was observed irrespective of the methods. Respirable fraction
      (RF) varied from 34 to 73% in case of nebulizer and from 47 to 54% in case of
      DPI. In vivo deposition of voriconazole in lungs was found to be 80-130 ug/g of
      lung tissue in case of DPI and 40-68 ug/g of lung tissue in case of using
      nebulizer. DISCUSSION: DPI designed was efficient in fluidizing powder bed and
      dispensing dry powder for inhalation. The inhalation chamber designed was
      efficient in uniformly distributing drug in various inhalation ports of the
      chamber. CONCLUSIONS: The DPI and inhalation chamber designed can be successfully
      used for inhalation study with multiple animals especially mice.

PMID- 21721852
TI  - Nanoparticle-mediated delivery of neurotoxin-II to the brain with intranasal
      administration: an effective strategy to improve antinociceptive activity of
      neurotoxin.
AB  - BACKGROUND: Neurotoxin-II (NT-II), an analgesic peptide which was separated from
      the venom of Naja naja atra, is endowed an exceptional specificity of action that
      block transmission of the nerve impulse by binding to the acetylcholine receptor
      in the membrane. However, it has limited permeability across the blood-brain
      barrier (BBB) after intravenously (i.v.) injection. METHODS: In this study, we
      explored the potential application of nanoparticles overcoated with polysorbate
      80 (P-80-NP) as drug carrier system for the nasal delivery of NT and the
      antinociceptive properties of NT-loaded P-80-NP (NT-P-NP) were also evaluated.
      RESULTS: The brain delivery of NT-II could be enhanced with nanoparticles coated
      with polysorbate-80 through intranasally (i.n.) administration. Compared with NT
      II solution, NT-P-NP exhibited sustained release in vitro and higher
      concentrations of NT-II in the brain. The antinociceptive animal testing also
      revealed that intranasal delivery of NT-loaded nanoparticle coated with
      polysorbate-80 were able to promote better biodistribution of the drug into the
      brain. CONCLUSION: The nanoparticles overcoated with polysorbate-80 were capable
      of transporting the loaded drug across the BBB after intranasal administration.

PMID- 21721853
TI  - Daily rhythmic expression patterns of clock1a, bmal1, and per1 genes in retina
      and hypothalamus of the rainbow trout, Oncorhynchus mykiss.
AB  - Living organisms show daily rhythms in physiology, behavior, and gene expression,
      which are due to the presence of endogenous clocks that synchronize biological
      processes to the 24-h light/dark cycle. In metazoans, generation of circadian
      rhythmicity is a consequence of specialized tissues known as "master clocks,"
      having different locations among species. A few studies have described clock-gene
      expression in fish neural tissues, but none of them assessed clock-gene
      expression in different discrete regions. The present study was designed to
      explore the presence/absence of circadian clock-gene expression in the rainbow
      trout (Oncorhynchus mykiss) retina and hypothalamus. Juvenile fish were
      acclimated to a 12:12 light (L)-dark (D) cycle. Then, retina and hypothalamus
      were collected from animals kept under LD conditions or constant darkness (DD)
      for 24 h. Real-time quantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) assays were performed to quantify expression of the core circadian genes
      Clock1a, Bmal1, and Per1 as representative members of the circadian oscillator.
      All clock genes analyzed in the retina and hypothalamus showed circadian
      fluctuations. However, gene expression peaked in the rainbow trout hypothalamus
      with a 3-h (Clock1a and Bmal1) or 6-h (Per1) delay relative to that observed in
      the retina, the latter showing highest expression levels at zeitgeber times 9
      (ZT9) for Clock1a and Bmal1, and at ZT21 for Per1. When exposed to DD, the
      rhythmic gene expression pattern was maintained for all genes in the rainbow
      trout retina, but only for Clock1a and Per1 in the hypothalamus. Bmal1 failed to
      cycle under DD, suggesting that hypothalamic clock function might depend on
      either several clock-gene isoforms or regulation from external inputs. Overall,
      these data indicate that representative molecular members of the core circadian
      clock are present in both the retina and hypothalamus of rainbow trout.

PMID- 21721854
TI  - Varying the length of dim nocturnal illumination differentially affects the
      pacemaker controlling the locomotor activity rhythm of Drosophila jambulina.
AB  - Photic entrainment of animals in the field is basically attributed to their
      exposure to the dimly lit nights flanked by the dawn and dusk twilight
      transitions. This implicates the functional significance of the dimly lit nights
      as that of the twilight transitions. Recently, the authors have demonstrated that
      the dimly lit night at 0.0006 lux altered the attributes of the circadian rhythm
      of locomotor activity of Drosophila jambulina. The present study examined whether
      the durations of such dimly lit nights affect the entrainment and free-running
      rhythmicity of D. jambulina. Flies were subjected for 10 days to two types of 24
      h lighting regimes in which the photophase (L) was at 10 lux for all flies but
      the scotophase, which varied in duration from 9 to 15 h, was either at 0 lux (D
      phase) for control flies or 0.0006 lux (the artificial starlight or S phase) for
      experimental flies. Thereafter, they were transferred to constant darkness (DD)
      to compare the after-effects of the dimly lit nights on the period (tau) of free
      running rhythm in DD with that of the completely dark nights. Control flies were
      entrained by all LD cycles, but the experimental flies were entrained only by
      five LS cycles in which the duration of the S phases ranged from 10 to 14 h. The
      two LS cycles with very short (9 h) and long (15 h) S phases rendered the flies
      completely arrhythmic. Control flies started activity shortly before lights-on
      and continued well after lights-off. The experimental flies, however, commenced
      activity several hours prior to lights-on but ended activity abruptly at lights
      off as the result of a negative masking effect of nocturnal illumination. Length
      of the midday rest was considerably shorter in the control than in the
      experimental flies in each lighting regime. The active phase in the control flies
      was predictably shortened; nonetheless, it was invariable in the experimental
      flies as the nights lengthened. Transfer from lighting regimes to DD initiated
      robust free-running rhythmicity in all flies including the arrhythmic ones
      subjected to LS cycles with 9 and 15 h of scotophases. The tau was profoundly
      affected by the nocturnal irradiance of the prior entraining lighting regime, as
      it was always shorter in the experimental than in the control flies. Thus, these
      results indisputably demonstrate the changes in fundamental properties of the
      circadian pacemaker of D. jambulina were solely attributed to the extremely dim
      nocturnal irradiance. This strain of D. jambulina is entrained essentially by the
      dimly lit natural nights, since it is never exposed to the prevailing photic cues
      such as the twilight transitions or bright photoperiod, owing to the dense
      vegetation of its habitat.

PMID- 21721855
TI  - Circadian modulation of acute alcohol sensitivity but not acute tolerance in
      Drosophila.
AB  - An increased understanding of the factors affecting behavioral and neurological
      responses to alcohol and alcohol physiology is necessary given the tremendous
      toll alcohol abuse and alcoholism exert on individuals and society. At the
      behavioral and molecular levels, the response to alcohol appears remarkably
      conserved from Drosophila to humans, suggesting that investigations across model
      species can provide insight into the identification of common modulatory factors.
      We investigated the interaction between the circadian clock and alcohol
      sensitivity, alcohol tolerance, and alcohol absorbance in Drosophila
      melanogaster. Using a loss-of-righting reflex (LoRR) assay, we found that flies
      exhibit a circadian rhythm in the LoRR, with the greatest sensitivity to alcohol
      occurring from mid to late night, corresponding to the flies' inactive phase. As
      predicted, a circadian rhythm in the LoRR was absent in circadian mutant flies
      and under conditions in which the circadian clock was nonfunctional. Circadian
      modulation of the response to alcohol was not due to circadian regulation of
      alcohol absorbance. Similar to other animals, Drosophila develop acute and
      chronic tolerance to alcohol upon repeat exposures. We found that the circadian
      clock did not modulate the development of acute alcohol tolerance measured as the
      difference in sensitivity to alcohol between naive and pre-exposed flies. Thus,
      the circadian clock modulates some, but not all, of the behavioral responses to
      alcohol exposure, suggesting that specific mechanisms underlie the observed
      circadian modulation of LoRR rather than global cellular circadian regulation.
      This study provides valuable new insights in our understanding of the circadian
      modulation of alcohol-induced behaviors that ultimately could facilitate
      preventative measures in combating alcohol abuse and alcoholism.

PMID- 21721856
TI  - Human cone light sensitivity and melatonin rhythms following 24-hour continuous
      illumination.
AB  - This study investigates the possibility of an endogenous circadian rhythm in
      retinal cone function in humans. A full-field cone electroretinogram (ERG) was
      performed every 2 h for 24 h under continuous rod-saturating ambient white light
      (53 +/- 30 lux; pupils dilated) in nine healthy subjects. Distinct circadian
      variations were superimposed upon a gradual decrease in cone responsiveness to
      light, demonstrated most reliably in the implicit times of b-wave and oscillatory
      potentials, and to a lesser extent in amplitude and a-wave implicit times. After
      mathematical correction of the linear trend, the cone response was found to be
      greatest around 20:00 h and least around 06:00 h. The phase of the ERG circadian
      rhythm was not synchronized with the phase of the salivary melatonin rhythm
      measured the previous evening. Melatonin levels measured under constant light on
      the day of ERG assessments were suppressed by 53% on average compared to
      melatonin profiles obtained previously under near-total darkness in seven
      participants. The progressive decline in cone responsiveness to light over the 24
      h may reflect an adaptation of the cone-driven retinal system to constant light,
      although the mechanism is unclear. The endogenous rhythm of cone responsiveness
      to light may be used as an additional index of central or retinal circadian clock
      time.

PMID- 21721857
TI  - Reduced phase-advance of plasma melatonin after bright morning light in the
      luteal, but not follicular, menstrual cycle phase in premenstrual dysphoric
      disorder: an extended study.
AB  - The authors previously observed blunted phase-shift responses to morning bright
      light in women with premenstrual dysphoric disorder (PMDD). The aim of this study
      was to determine if these findings could be replicated using a higher-intensity,
      shorter-duration light pulse and to compare these results with the effects of an
      evening bright-light pulse. In 17 PMDD patients and 14 normal control (NC)
      subjects, the authors measured plasma melatonin at 30-min intervals from 18:00 to
      10:00 h in dim (<30 lux) or dark conditions the night before (Night 1) and after
      (Night 3) a bright-light pulse (administered on Night 2) in both follicular and
      luteal menstrual cycle phases. The bright light (either 3000 lux for 6 h or 6000
      lux for 3 h) was given either in the morning (AM light), 7 h after the dim light
      melatonin onset (DLMO) measured the previous month, or in the evening (PM light),
      3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light
      advanced melatonin offset between Night 1 and Night 3 significantly less in PMDD
      than in NC subjects. The effects of PM light were not significant, nor were there
      significant effects of the light pulse on melatonin measures of onset, duration,
      peak, or area under the curve. These findings replicated the authors' previous
      finding of a blunted phase-shift response to morning bright light in the luteal,
      but not the follicular, menstrual cycle phase in PMDD compared with NC women,
      using a brighter (6000 vs. 3000 lux) light pulse for a shorter duration (3 vs. 6
      h). As the effect of PM bright light on melatonin phase-shift responses did not
      differ between groups or significantly alter other melatonin measures, these
      results suggest that in PMDD there is a luteal-phase subsensitivity or an
      increased resistance to morning bright-light cues that are critical in
      synchronizing human biological rhythms. The resulting circadian rhythm
      malsynchonization may contribute to the occurrence of luteal phase depressive
      symptoms in women with PMDD.

PMID- 21721858
TI  - Differences in daily rhythms of wrist temperature between obese and normal-weight
      women: associations with metabolic syndrome features.
AB  - The circadian rhythm of core body temperature is associated with widespread
      physiological effects. However, studies with other more practical temperature
      measures, such as wrist (WT) and proximal temperatures, are still scarce. The aim
      of this study was to investigate whether obesity is associated with differences
      in mean WT values or in its daily rhythmicity patterns. Daily patterns of
      cortisol, melatonin, and different metabolic syndrome (MetS) features were also
      analyzed in an attempt to clarify the potential association between
      chronodisruption and MetS. The study was conducted on 20 normal-weight women
      (age: 38 +/- 11 yrs and BMI: 22 +/- 2.6 kg/m(2)) and 50 obese women (age: 42 +/-
      10 yrs and BMI: 33.5 +/- 3.2 kg/m(2)) (mean +/- SEM). Skin temperature was
      measured over a 3-day period every 10 min with the "Thermochron iButton."
      Rhythmic parameters were obtained using an integrated package for time-series
      analysis, "Circadianware." Obese women displayed significantly lower mean WT
      (34.1 degrees C +/- 0.3 degrees C) with a more flattened 24-h pattern, a lower
      quality rhythm, and a higher intraday variability (IV). Particularly interesting
      were the marked differences between obese and normal-weight women in the
      secondary WT peak in the postprandial period (second-harmonic power [P2]),
      considered as a marker of chronodisruption and of metabolic alterations. WT
      rhythmicity characteristics were related to MetS features, obesity-related
      proteins, and circadian markers, such as melatonin. In summary, obese women
      displayed a lower-quality WT daily rhythm with a more flattened pattern
      (particularly in the postprandial period) and increased IV, which suggests a
      greater fragmentation of the rest/activity rhythm compared to normal-weight
      women. These 24-h changes were associated with higher MetS risk.

PMID- 21721859
TI  - Hypobaric impact on clinical tolerance and 24-h patterns in iron metabolism
      markers and plasma proteins in men.
AB  - Long-distance flights can cause a number of clinical problems due to mild hypoxia
      resulting from cabin pressurization. Using a chronobiological approach, the aim
      of this work was to assess the clinical tolerance and biological impact of
      daytime exposure to hypobaric hypoxia on markers of iron metabolism and plasma
      proteins. Fourteen healthy, male volunteers, ages 23 to 39 yrs, spent 8.5 h in a
      hypobaric chamber (from 07:45 to 16:15 h) simulating an altitude of 8000 ft. This
      was followed by another 8.5-h session 4 wks later simulating conditions at an
      altitude of 12,000 ft. Biological variables were assayed every 2 h over two 24-h
      spans (control and hypoxia spans, respectively) per simulated altitude. Whereas
      most of the subjects tolerated the 8000 ft exposure well, eight subjects (57%)
      presented clear clinical signs of hypoxic intolerance at 12,000 ft. The 24-h
      blood iron profile showed a biphasic pattern at both altitude simulations, with a
      significant (~40%) increase during hypoxia, followed by a (~25%) decrease during
      the first hours of recovery. The iron circadian rhythm showed a significant phase
      delay during the hypoxic exposure at 8000 ft vs. reference. Mean 24-h ferritin
      levels decreased at both altitudes, but mainly during the nighttime after the
      12,000 ft exposure in accordance with Cosinor analysis. The transferrin and total
      plasma proteins 24-h profiles did not show significant change. Moreover,
      significant differences, mainly in iron, ferritin, and transferrin, were found at
      12,000 ft according to the clinical tolerance to hypoxia, and significant
      correlations were found between the mid-range crossing times, i.e., here half
      descent times (d-T(50)), for ferritin and total plasma proteins and the reported
      level of clinical discomfort under hypoxia. This study shows that an 8.5-h
      exposure to mild hypoxia is able to alter very quickly the 24-h pattern of iron
      and ferritin. These alterations seem to depend, at least in part, on the clinical
      tolerance to hypoxia and may help explain the interindividual differences
      observed in the tolerance to hypoxia.

PMID- 21721860
TI  - Shiftwork duration and the awakening cortisol response among police officers.
AB  - Police officers are required to work irregular hours, which induces stress,
      fatigue, and sleep disruption, and they have higher rates of chronic disease and
      mortality. Cortisol is a well-known "stress hormone" produced via activation of
      the hypothalamic-pituitary-adrenal axis. An abnormal secretion pattern has been
      associated with immune system dysregulation and may serve as an early indicator
      of disease risk. This study examined the effects of long- and short-term
      shiftwork on the cortisol awakening response among officers (n = 68) in the
      Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study (2001
      2003). The time each officer spent on day (start time: 04:00-11:59 h), afternoon
      (12:00-19:59 h), or night (20:00-03:59 h) shifts was summarized from 1994 to
      examination date to characterize long-term (mean: 14 +/- 9 yrs) and short-term
      (3, 5, 7, or 14 days prior to participation) shiftwork exposures. The cortisol
      awakening response was characterized by summarizing the area under the curve
      (AUC) for samples collected on first awakening, and at 15-, 30-, and 45-min
      intervals after waking. Data were collected on a scheduled training or off day.
      The cortisol AUC with respect to ground (AUC(G)) summarized total cortisol output
      after waking, and the cortisol AUC with respect to increase (AUC(I))
      characterized the waking cortisol response. Officers also completed the Center
      for Epidemiologic Studies Depression scale. Waking cortisol AUC values were lower
      among officers working short-term night or afternoon shifts than day shifts, with
      maximal differences occurring after 5 days of shiftwork. The duration of long
      term shiftwork was not associated with the cortisol awakening response, although
      values were attenuated among officers with more career shift changes.

PMID- 21721861
TI  - Sex and dosing-time dependencies in irinotecan-induced circadian disruption.
AB  - Circadian disruption accelerates malignant growth; thus, it should be avoided in
      anticancer therapy. The circadian disruptive effects of irinotecan, a
      topoisomerase I inhibitor, was investigated according to dosing time and sex. In
      previous work, irinotecan achieved best tolerability following dosing at
      zeitgeber time (ZT) 11 in male and ZT15 in female mice, whereas worst toxicity
      corresponded to treatment at ZT23 and ZT3 in male and female mice, respectively.
      Here, irinotecan (50 mg/kg intravenous [i.v.]) was delivered at the sex-specific
      optimal or worst circadian timing in male and female B6D2F1 mice. Circadian
      disruption was assessed with rest-activity, body temperature, plasma
      corticosterone, and liver mRNA expressions of clock genes Rev-erbalpha, Per2, and
      Bmal1. Baseline circadian rhythms in rest-activity, body temperature, and plasma
      corticosterone were more prominent in females as compared to males. Severe
      circadian disruption was documented for all physiology and molecular clock
      endpoints in female mice treated at the ZT of worst tolerability. Conversely,
      irinotecan administration at the ZT of best tolerability induced slight
      alteration of circadian physiology and clock-gene expression patterns in female
      mice. In male mice, irinotecan produced moderate alterations of circadian
      physiology and clock-gene expression patterns, irrespective of treatment ZT.
      However, the average expression of Rev-erbalpha, Per2, and Bmal1 were down
      regulated 2- to 10-fold with irinotecan at the worst ZT, while being minimally or
      unaffected at the best ZT, irrespective of sex. Corticosterone secretion
      increased acutely within 2 h with a sex-specific response pattern, resulting in a
      ZT-dependent phase-advance or -delay in both sex. The mRNA expressions of
      irinotecan clock-controlled metabolism genes Ce2, Ugt1a1, and Top1 were unchanged
      or down-regulated according to irinotecan timing and sex. This study shows that
      the circadian timing system represents an important toxicity target of irinotecan
      in female mice, where circadian disruption persists after wrongly timed
      treatment. As a result, the mechanisms underling cancer chronotherapeutics are
      expectedly more susceptible to disruption in females as compared to males. Thus,
      the optimal circadian timing of chemotherapy requires precise determination
      according to sex, and should involve the noninvasive monitoring of circadian
      biomarkers.

PMID- 21721862
TI  - Light, clocks, mood, and cancer: consolidation and novel tests of latitude and
      instability hypotheses.

PMID- 21721864
TI  - Overtime working hours and depression: questionnaire survey using the patient
      health questionnaire (PHQ-9).

PMID- 21721866
TI  - Rathke cleft cysts: a review of clinical and surgical management.
AB  - The aim of this paper is to provide a comprehensive review of clinical, imaging,
      and histopathological features, as well as operative and nonoperative management
      strategies in patients with Rathke cleft cysts (RCCs). A literature review was
      performed to identify previous articles that reported surgical and nonsurgical
      management of RCCs. Rathke cleft cysts are often incidental lesions found in the
      sellar and suprasellar regions and do not require surgical intervention in the
      majority of cases. In symptomatic RCCs, the typical clinical presentation
      includes headache, visual loss, and/or endocrine dysfunction. Visual field
      testing and endocrine laboratory studies may reveal more subtle deficiencies
      associated with RCCs. When indicated, the transsphenoidal approach typically
      offers the least invasive and safest method for treating these lesions. Various
      surgical strategies including cyst wall resection, intralesional alcohol
      injection, and sellar floor reconstruction are discussed. Although headache and
      visual symptoms frequently improve after surgical drainage of RCCs,
      hypopituitarism and diabetes insipidus are less likely to do so. A subset of more
      aggressive, atypical RCCs associated with pronounced clinical symptoms and higher
      recurrence rates is discussed, as well as the possible relationship of these
      lesions to craniopharyngiomas. Rathke cleft cysts are typically benign,
      asymptomatic lesions that can be monitored. In selected patients, transsphenoidal
      surgery provides excellent rates of improvement in clinical symptoms and long
      term cyst resolution. Complete cyst wall resection, intraoperative alcohol
      cauterization, and sellar floor reconstruction in the absence of a CSF leak are
      not routinely recommended.

PMID- 21721867
TI  - Symptomatic Rathke cleft cysts: extent of resection and surgical complications.
AB  - OBJECT: Rathke cleft cysts (RCCs) are benign masses arising from the
      embryological Rathke pouch, and are commonly treated by transsphenoidal surgery.
      The authors retrospectively compared RCC extent of resection-either gross-total
      resection (GTR) or decompression-to the primary outcome measure, which was
      recurrences resulting in repeat surgery, and the secondary outcome measure, which
      was complications. METHODS: Seventy-four patients presenting to the neurosurgical
      department with RCC were analyzed retrospectively. Sixty-eight patients had a
      total of 78 surgical procedures, with the diagnosis of RCC confirmed by
      histological investigation; of these, 61 patients had adequate operative notes
      for the authors to evaluate extent of resection. Groups were separated into GTR
      (32 patients) or decompression (subtotal resection or fenestration into the
      sphenoid sinus; 29 patients) based on operative notes and postoperative imaging.
      The mean follow-up duration was 60.5 +/- 72.1 months (the mean is expressed +/-
      SD throughout). RESULTS: The average age at the time of the initial surgery was
      42.8 +/- 17.4 years, and 70% of patients were female. The mean cyst diameter
      preoperatively was 16.9 +/- 17.8 mm. Eight patients had repeat surgery, our
      primary outcome measure; 3 repeat operations occurred in the GTR group, and 5 in
      the decompression group. There was no significant difference in recurrence when
      comparing groups (GTR 9%, decompression 17%; p = 0.36). There were no major
      complications; however, analysis of postoperative minor complications revealed
      that 11 (34%) GTRs resulted in surgical complications, whereas the decompression
      cohort accounted for only 3 complications (10%) (p = 0.03), with diabetes
      insipidus (6) and CSF leaks (5) being the most common. Gross-total resection also
      resulted in an increase in postoperative hyperprolactinemia compared with
      decompression (p = 0.03). CONCLUSIONS: It appears that RCCs require repeat
      surgery in 13% of cases, and attempted GTR does not appear to reduce the overall
      rate of recurrence. However, more aggressive resections are associated with more
      complications in this series.

PMID- 21721868
TI  - Rathke cleft cysts in pediatric patients: presentation, surgical management, and
      postoperative outcomes.
AB  - OBJECT: Rathke cleft cysts (RCC) are benign sellar lesions most often found in
      adults, and more infrequently in children. They are generally asymptomatic but
      sometimes require surgical treatment through a transsphenoidal corridor. The
      purpose of this study was to compare adult versus pediatric cases of RCC.
      METHODS: The authors retrospectively reviewed presenting symptoms, MR imaging
      findings, laboratory study results, and pathological findings in 147 adult and 14
      pediatric patients who underwent surgery for treatment of RCCs at the University
      of Californial at San Francisco between 1996 and 2008. RESULTS: In both the adult
      and pediatric groups, most patients were female (78% of adults, 79% of pediatric
      patients, p = 0.9). Headache was the most common symptom in both groups (reported
      by 50% of pediatric patients and 33% of adults, p = 0.2). Preoperative
      hypopituitarism occurred in 41% of adults and 45% of pediatric patients (p =
      0.8). Growth delay, a uniquely pediatric finding, was a presenting sign in 29% of
      pediatric patients. Visual complaints were a presenting symptom in 16% of adult
      and 7% of pediatric patients (p = 0.4). There was no difference between median
      cyst size in adults versus pediatric patients (1.2 cm in both, p = 0.7).
      Temporary or permanent postoperative diabetes insipidus occurred in 12% of adults
      and 21% of pediatric patients (p = 0.4). Kaplan-Meier analysis revealed an 8% RCC
      recurrence rate at 2 years for each group (p = 0.5). CONCLUSIONS: The incidence
      of RCCs is much lower in the pediatric population; however, symptoms, imaging
      findings, and outcomes are similar, suggesting that pediatric RCCs arise from
      growth of remnants of the embryonic Rathke pouch earlier in life than adult RCCs
      but do not differ in any other way. It is important to consider RCCs in the
      differential diagnosis when pediatric patients present with visual impairment,
      unexplained headache, or hypopituitarism including growth delay. Although the
      average RCC size was similar in our pediatric and adult patient groups, the
      smaller size of the pituitary gland in pediatric patients suggests an increased
      relative RCC size.

PMID- 21721869
TI  - Rathke cleft cyst presenting with hyponatremia: an unusual presentation.
AB  - The authors report a case of Rathke cleft cyst presenting with severe
      hyponatremia. A 33-year-old man suffered sudden severe headaches, visual changes,
      dizziness, nausea, vomiting, and a metallic taste in his mouth. Initial
      laboratory values demonstrated severe hyponatremia. Magnetic resonance imaging
      revealed a cystic lesion with questionable intracystic hemorrhage, concerning for
      pituitary apoplexy. Transsphenoidal decompression and drainage of the cyst
      confirmed the diagnosis of Rathke cleft cyst and resolved the symptoms.
      Postoperative follow-up studies at 6 months demonstrated normal endocrine
      function and no evidence of a cyst.

PMID- 21721870
TI  - Rathke cleft cysts.

PMID- 21721871
TI  - Diagnosis and treatment of ossification of the ligamentum flavum associated with
      dural ossification: clinical article.
AB  - OBJECT: In this paper, the authors aimed to summarize the clinical
      characteristics of ossification of the ligamentum flavum (OLF) associated with
      dural ossification (DO) and to identify improved methods for preoperative
      diagnosis. METHODS: Thirty-six patients who had undergone OLF surgery between
      February 2005 and September 2009 were included in this retrospective study. The
      patients were divided into 2 groups: one that included patients with
      intraoperative evidence of DO and a second group that included patients without
      DO. The clinical features of DO were summarized and the neurological status of
      the patients was evaluated pre- and postoperatively. RESULTS: The incidence rate
      of DO associated with OLF was 39% (14/36). The sensitivity and specificity of the
      tram track sign were found to be 93% and 59%, respectively. Dural ossification
      was found among 86% of the patients with tuberous type Sato classification. The
      postoperative neurological status of patients was generally improved relative to
      that observed prior to surgery, although neurological recovery did not differ
      between the 2 groups. Cerebrospinal fluid leakage was the main complication,
      occurring predominantly in the patients with DO, and all leaks resolved in all
      patients after comprehensive treatments. CONCLUSIONS: The tram track sign and
      Sato classification were found to be useful for preoperative diagnosis of DO and
      for determining the surgical procedure to be performed. Dural ossification had no
      effect on postoperative neurological recovery.

PMID- 21721872
TI  - Time course investigation of intervertebral disc degeneration produced by needle
      stab injury of the rat caudal spine: laboratory investigation.
AB  - OBJECT: In this study, the authors' goal was to investigate the long-term
      progression of disc degeneration and the participating mechanisms induced by
      needle puncture in a rat caudal disc model. METHODS: The C5-6 and C7-8
      intervertebral discs of the caudal spine in rats were stabbed laterally using 21
      gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with
      the aid of fluoroscopy. Signs of degeneration in the disc of the tail were
      analyzed from Day 1 to Week 30 by in vivo MR imaging, histology, and biochemical
      and/or molecular analyses. RESULTS: Magnetic resonance imaging showed a
      progressive decrease in T2 density and MR imaging index throughout the entire
      investigation, starting at Day 1 after the needle puncture. However, histological
      scores revealed a bimodal pattern, showing that severity increased in the first
      17 days, declined thereafter, and increased again by 30 weeks. Gene expression
      analysis showed a transient up-regulation in gene expression of aggrecan, type II
      collagen, and BMP-2, and inhibition of type I collagen. The MMP-3 mRNA levels
      were up-regulated at all tested time points within 6 weeks postinjury.
      Furthermore, the degenerated disc did not recover spontaneously, as shown by
      decreases in T2 density, MR imaging index, and sulfated glycosaminoglycan content
      in conjunction with increases in histological scores at 15 and 30 weeks
      postsurgery. CONCLUSIONS: This study demonstrates that needle puncture into a
      tail disc in the rat induces a rapid and progressive disc degeneration process
      without spontaneous recovery. Changes in gene expression profiles of the disc
      matrix molecules as well as anabolic and catabolic factors at early time points
      further delineate the mechanism of disc degeneration in this newly developed
      animal model.

PMID- 21721873
TI  - Neuroprotective effects of granulocyte colony-stimulating factor and relationship
      to promotion of angiogenesis after spinal cord injury in rats: laboratory
      investigation.
AB  - OBJECT: Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects
      on the CNS. The authors have previously demonstrated that G-CSF also exerts
      neuroprotective effects in experimental spinal cord injury (SCI) by enhancing
      migration of bone marrow-derived cells into the damaged spinal cord, increasing
      glial differentiation of bone marrow-derived cells, enhancing antiapoptotic
      effects on both neurons and oligodendrocytes, and by reducing demyelination and
      expression of inflammatory cytokines. Because the degree of angiogenesis in the
      subacute phase after SCI correlates with regenerative responses, it is possible
      that G-CSF's neuroprotective effects after SCI are due to enhancement of
      angiogenesis. The aim of this study was to assess the effects of G-CSF on the
      vascular system after SCI. METHODS: A contusive SCI rat model was used and the
      animals were randomly allocated to either a G-CSF-treated group or a control
      group. Integrity of the blood-spinal cord barrier was evaluated by measuring the
      degree of edema in the cord and the volume of extravasation. For histological
      evaluation, cryosections were immunostained with anti-von Willebrand factor and
      the number of vessels was counted to assess revascularization. Real-time reverse
      transcriptase polymerase chain reaction was performed to assess expression of
      angiogenic cytokines, and recovery of motor function was assessed with function
      tests. RESULTS: In the G-CSF-treated rats, the total number of vessels with a
      diameter > 20 MUm was significantly larger and expression of angiogenic cytokines
      was significantly higher than those in the control group. The G-CSF-treated group
      showed significantly greater recovery of hindlimb function than the control
      group. CONCLUSIONS: These results suggest that G-CSF exerts neuroprotective
      effects via promotion of angiogenesis after SCI.

PMID- 21721874
TI  - Neurosurgery and shaving.

PMID- 21721875
TI  - Neurosurgery and shaving: what's the evidence?
AB  - Many neurosurgeons remove their patients' hair before surgery. They claim that
      this practice reduces the chance of postoperative surgical site infections, and
      facilitates planning, attachment of the drapes, and closure. However, most
      patients dread this procedure. The authors performed the first systematic review
      on shaving before neurosurgical procedures to investigate whether this commonly
      performed procedure is based on evidence. They systematically reviewed the
      literature on wound infections following different shaving strategies. Data on
      the type of surgery, surgeryrelated infections, preoperative shaving policy,
      decontamination protocols, and perioperative antibiotics protocols were
      collected. The search detected 165 articles, of which 21 studies-involving 11,071
      patients-were suitable for inclusion. Two of these studies were randomized
      controlled trials. The authors reviewed 13 studies that reported on the role of
      preoperative hair removal in craniotomies, 14 on implantation surgery, 5 on bur
      hole procedures, and 3 on spine surgery. Nine studies described shaving policies
      in pediatric patients. None of these papers provided evidence that preoperative
      shaving decreases the occurrence of postoperative wound infections. The authors
      conclude that there is no evidence to support the routine performance of
      preoperative hair removal in neurosurgery. Therefore, properly designed studies
      are needed to provide evidence for preoperative shaving recommendations.

PMID- 21721876
TI  - Neoplastic meningitis.

PMID- 21721877
TI  - Transient bilateral brainstem dysfunction caused by topical administration of
      papaverine.
AB  - Papaverine has been associated with transient cranial nerve dysfunction after
      topical application during craniotomy. The authors report similar dysfunction
      after the use of papaverine affected brainstem structures. Two patients
      undergoing craniotomy for clipping of an aneurysm experienced bilateral
      depression of cortical somatosensory evoked potentials to both median and tibial
      nerve stimulation after administration of papaverine. Arterial blood gas
      analysis, hemodynamic parameters, and anesthetic levels remained constant
      throughout these somatosensory evoked potential changes. In addition,
      intraoperative angiography and immediate postoperative CT imaging showed intact
      blood flow with complete exclusion of the aneurysm. Both patients recovered
      within 1-2 hours and had normal neurological examination findings after
      extubation. Topical papaverine use may be associated with direct effects on
      brainstem structures. The transient nature of those changes suggests that
      aggressive intervention may not be needed. Maneuvers to limit the spread of
      papaverine to basal cisterns should be considered.

PMID- 21721878
TI  - Benefit of ventriculoperitoneal cerebrospinal fluid shunting and intrathecal
      chemotherapy in neoplastic meningitis: a retrospective, case-controlled study.
AB  - OBJECT: Neoplastic meningitis (NM) is a debilitating and increasingly frequent
      neurological complication of cancer characterized by infiltration of tumor cells
      into the leptomeninges and the subarachnoid space. Although NM is rarely curable,
      combined intrathecal chemotherapy and focal radiation can improve disease-related
      symptoms and survival. Hydrocephalus occurs in a significant proportion of
      patients, is associated with poor prognosis and reduced quality of life, and
      usually precludes the use of intrathecal therapy. METHODS: Since January of 2005,
      the authors have used a combined treatment approach for patients with both NM and
      hydrocephalus that employs a subcutaneously placed reservoir connected in series
      to an on/off valve and a ventriculoperitoneal shunt for both diversion of CSF and
      injection of intrathecal chemotherapy. They conducted a retrospective, case
      controlled study from 2 independent institutions to review their experience.
      RESULTS: Twenty-four patients with NM and hydrocephalus underwent placement of a
      CSF reservoir-on/off valve-ventriculoperitoneal shunt (RO-VPS) construct. There
      was no perioperative mortality, and there were only 2 minor complications. One
      shunt failure and no shunt-associated infections were observed over a median of
      28 weeks of follow-up. Symptomatic improvement and improved performance status
      were seen in 20 patients (83.3%) and were sustained over 6 months. Eighteen
      patients received intraventricular chemotherapy without unexpected toxicity, and
      cytological responses were found in 11 patients (61.1%). Median progression-free
      and overall survival was 14 and 31 weeks, respectively. Compared with a
      contemporaneous comparison group of 24 demographically matched patients with NM
      who underwent CSF reservoir placement only, those who received RO-VPS constructs
      (p = 0.02) and had primary diagnosis of breast cancer (p = 0.04) had significant
      advantage in overall survival. CONCLUSIONS: A combined RO-VPS system is safe and
      practical to install, results in symptomatic improvement in most patients, and
      allows uncomplicated and effective administration of intrathecal chemotherapy in
      patients with NM. Cerebrospinal fluid diversion surgery should be considered in
      NM patients in conjunction with intrathecal and systemic treatments.

PMID- 21721879
TI  - Antitumor effect of aspirin in glioblastoma cells by modulation of beta-catenin/T
      cell factor-mediated transcriptional activity.
AB  - OBJECT: The goal in this study was to investigate the antitumor effect of aspirin
      in glioblastoma cells and the molecular mechanism involved in its antineoplastic
      activities. METHODS: The authors used the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide method, flow cytometry, the annexin V method, and
      Transwell cell invasion test to detect the proliferation and invasive activity of
      U87 and A172 glioma cells before and after being treated with aspirin. To
      determine the effects of aspirin on beta-catenin/T-cell factor (TCF)
      transcription activity, reporter constructs containing 3 repeats of the wild-type
      (TOPflash) or mutant (FOPflash) TCF-binding sites were used. Reverse
      transcriptase polymerase chain reaction and Western blot analyses were used to
      detect the expression of multiple beta-catenin/TCF target genes following aspirin
      treatment. RESULTS: The transcriptional activity of the beta-catenin/TCF complex
      was strongly inhibited by aspirin. Increasing the concentration of aspirin
      resulted in decreased expression of c-myc, cyclin D1, and fra-1 mRNA and protein
      in U87 and A172 cells in a dose-dependent manner. Aspirin inhibited glioma cell
      proliferation and invasive ability, and induced apoptotic cell death.
      CONCLUSIONS: The results suggest that aspirin is a potent antitumor agent, and
      that it exerts its antineoplastic action by inhibition of the beta-catenin/TCF
      signaling pathway in glioma cells.

PMID- 21721880
TI  - Endoscopic third ventriculostomy.

PMID- 21721881
TI  - Pediatric Chiari malformation Type 0: a 12-year institutional experience.
AB  - OBJECT: In 1998 the authors identified 5 patients with syringomyelia and no
      evidence of Chiari malformation Type I (CM-I). Magnetic resonance imaging of the
      entire neuraxis ruled out other causes of a syrinx. Ultimately, abnormal CSF flow
      at the foramen magnum was the suspected cause. The label "Chiari 0" was used to
      categorize these unique cases with no tonsillar ectopia. All of the patients
      underwent posterior fossa decompression and duraplasty identical to the technique
      used to treat patients with CM-I. Significant syrinx and symptom resolution
      occurred in these patients. Herein, the authors report on a follow-up study of
      patients with CM-0 who were derived from over 400 operative cases of pediatric CM
      I decompression. METHODS: The authors present their 12-year experience with this
      group of patients. RESULTS: Fifteen patients (3.7%) were identified. At surgery,
      many were found to have physical barriers to CSF flow near the foramen magnum. In
      most of them, the syringomyelia was greatly diminished postoperatively.
      CONCLUSIONS: The authors stress that this subgroup represents a very small cohort
      among patients with Chiari malformations. They emphasize that careful patient
      selection is critical when diagnosing CM-0. Without an obvious CM-I, other
      etiologies of a spinal syrinx must be conclusively ruled out. Only then can one
      reasonably expect to ameliorate the clinical course of these patients via
      posterior fossa decompression.

PMID- 21721882
TI  - Endoscopic treatment of suprasellar arachnoid cysts in children.
AB  - OBJECT: Suprasellar arachnoid cysts (SACs) are rare, comprising approximately 10%
      of all intracranial arachnoid cysts. Although neuroendoscopic management is
      emerging as a safe effective alternative to microsurgery, the type of endoscopic
      surgery whether ventriculocystostomy (VC) or ventriculocystocisternostomy (VCC)
      is still controversial. This study evaluates the role of endoscopy in the
      treatment of SACs in children. It compares VC and VCC to determine which
      procedure is superior in the long term. METHODS: Twenty-five children (14 boys
      and 11 girls; mean age 26 months) with symptomatic SACs associated with
      hydrocephalus are the subject of this study. According to the surgical procedure
      adopted, patients were divided into 2 groups. Patients in Group A (11 patients)
      underwent VC with a mean follow-up of 55 months, and those in Group B (14
      patients) underwent VCC with a mean follow-up of 64.7 months. RESULTS: Both
      procedures proved to be effective clinically and radiologically. The incidence of
      improvement of hydrocephalus-related symptoms was 63.6% in Group A compared with
      85.7% in Group B. Improvement in cyst size and hydrocephalus after VC was 81.8%
      and 63.6%, respectively, compared with 100% and 85.7%, respectively, after VCC.
      There were no deaths or permanent morbidity, and no patient was left with a
      permanent shunt. Recurrence occurred in 3 cases after VC (27.3%), whereas no
      recurrence (0%) was encountered after VCC. At a second endoscopic procedure, the
      fenestration was found to be closed in all 3 recurrent cases. CONCLUSIONS: An
      endoscopic procedure is recommended in the treatment of SACs in children because
      it is simple, effective, minimally invasive, and associated with low morbidity
      and mortality rates. Both procedures, VC and VCC, proved to be almost equally
      effective clinically and radiologically. Nevertheless, because of the
      statistically significant difference between the incidence of recurrence after VC
      and VCC during long-term follow-up, the author concludes that VCC should be
      considered as the procedure of choice in the treatment of these cases. The
      important finding of reclosure of the VC fenestration in the recurrent cases
      underscores the significance of performing cystocisternostomy at initial surgery
      to guard against cyst recurrence.

PMID- 21721883
TI  - A novel method for stereotactic, endoscope-assisted transtentorial placement of a
      shunt catheter into symptomatic posterior fossa cysts.
AB  - OBJECT: Posterior fossa cysts are usually divided into Dandy-Walker
      malformations, arachnoid cysts, and isolated and/or trapped fourth ventricles.
      Shunt placement is a mainstay treatment for decompression of these fluid
      collections when their expansion becomes symptomatic. Although several techniques
      to drain symptomatic posterior fossa cysts have been described, each method
      carries its own advantages and disadvantages. This article describes an
      alternative technique. METHODS: In 10 patients, the authors used an alternative
      technique involving stereotactic and endoscopic methods to place a catheter in
      symptomatic posterior fossa cysts across the tentorium. Discussion of these cases
      is included, along with a review of various approaches to shunt placement in this
      region and recommendations regarding the proposed technique. RESULTS: No patient
      suffered intracranial hemorrhage related to the procedure and catheter
      implantation. All 3 patients who underwent placement of a new transtentorial
      cystoperitoneal shunt and a new ventriculoperitoneal shunt did not suffer any
      postoperative complication; a decrease in the size of their posterior fossa cysts
      was evident on CT scans obtained during the 1st postoperative day. Follow-up CT
      scans demonstrated either stable findings or further interval decrease in the
      size of their cysts. In 1 patient, the postoperative head CT demonstrated that
      the transtentorial catheter terminated posterior to the right parietal occipital
      region without entering the retrocerebellar cyst. This patient underwent a repeat
      operation for proximal shunt revision, resulting in an acceptable catheter
      implantation. The patient in Case 8 suffered from a shunt infection and
      subsequently underwent hardware removal and aqueductoplasty with stent placement.
      The patient in Case 9 demonstrated a slight increase in fourth ventricle size and
      was returned to the operating room. Exploration revealed a kink in the tubing
      connecting the distal limb of the Y connector to the valve. The Y connector was
      replaced with a T connector, and 1 week later, CT scans exhibited interval
      decompression of the ventricles. This patient later presented with cranial wound
      breakdown and an exposed shunt. His shunt hardware was removed and he was treated
      with antibiotics. He later underwent reimplantation of a lateral ventricular and
      transtentorial shunt and suffered no other complications during a 3-year follow
      up period. CONCLUSIONS: The introduction of endoscopic and stereotactic
      techniques has expanded the available treatment possibilities for posterior fossa
      cysts.

PMID- 21721884
TI  - A standardized protocol to reduce cerebrospinal fluid shunt infection: the
      Hydrocephalus Clinical Research Network Quality Improvement Initiative.
AB  - OBJECT: Quality improvement techniques are being implemented in many areas of
      medicine. In an effort to reduce the ventriculoperitoneal shunt infection rate, a
      standardized protocol was developed and implemented at 4 centers of the
      Hydrocephalus Clinical Research Network (HCRN). METHODS: The protocol was
      developed sequentially by HCRN members using the current literature and prior
      institutional experience until consensus was obtained. The protocol was
      prospectively applied at each HCRN center to all children undergoing a shunt
      insertion or revision procedure. Infections were defined on the basis of CSF,
      wound, or pseudocyst cultures; wound breakdown; abdominal pseudocyst; or positive
      blood cultures in the presence of a ventriculoatrial shunt. Procedures and
      infections were measured before and after protocol implementation. RESULTS:
      Twenty-one surgeons at 4 centers performed 1571 procedures between June 1, 2007,
      and February 28, 2009. The minimum follow-up was 6 months. The Network infection
      rate decreased from 8.8% prior to the protocol to 5.7% while using the protocol
      (p = 0.0028, absolute risk reduction 3.15%, relative risk reduction 36%). Three
      of 4 centers lowered their infection rate. Shunt surgery after external
      ventricular drainage (with or without prior infection) had the highest infection
      rate. Overall protocol compliance was 74.5% and improved over the course of the
      observation period. Based on logistic regression analysis, the use of BioGlide
      catheters (odds ratio [OR] 1.91, 95% CI 1.19-3.05; p = 0.007) and the use of
      antiseptic cream by any members of the surgical team (instead of a formal
      surgical scrub by all members of the surgical team; OR 4.53, 95% CI 1.43-14.41; p
      = 0.01) were associated with an increased risk of infection. CONCLUSIONS: The
      standardized protocol for shunt surgery significantly reduced shunt infection
      across the HCRN. Overall protocol compliance was good. The protocol has
      established a common baseline within the Network, which will facilitate
      assessment of new treatments. Identification of factors associated with infection
      will allow further protocol refinement in the future.

PMID- 21721885
TI  - Giant syringobulbia associated with cerebellopontine angle arachnoid cyst and
      hydrocephalus.
AB  - The aim in reporting this case was to discuss the pathophysiology and treatment
      issues in an infant with a giant syringobulbia associated with a right
      cerebellopontine angle (CPA) arachnoid cyst causing noncommunicating
      hydrocephalus. This 7-month-old infant presented to the hospital with a history
      of delayed milestones and an abnormal increase in head circumference. Magnetic
      resonance images and CT scans of the brain showed a large CSF cavity involving
      the entire brainstem and a right CPA arachnoid cyst causing obstruction of the
      fourth ventricle and dilation of the lateral and third ventricles. Cerebrospinal
      fluid diversion was performed by direct communication from the syringobulbia
      cavity to the left lateral ventricle and from the left lateral ventricle through
      another ventricular catheter; external ventricular drainage was performed
      temporarily for 5 days. Communication between the syrinx and arachnoid cyst was
      confirmed. Clinically, there was a reduction in head circumference, and serial MR
      imaging of the brain showed a decrease in the size of the syrinx cavity and the
      ventricle along with opening of the normal CSF pathways. The postoperative course
      was uneventful, and no further intervention was necessary. On follow-up of the
      child at 3 years, his developmental milestones were normal. Surgical intervention
      for this condition is mandatory. The appropriate type of surgery should be
      performed on the basis of the pathophysiology of the developing syringobulbia.

PMID- 21721886
TI  - Preventing cerebrospinal fluid leak following transection of a tight filum
      terminale.
AB  - OBJECT: Tethered cord release for a tight filum terminale is a common pediatric
      operation associated with low morbidity and mortality rates. While almost all
      would agree that keeping patients lying flat after the operation will prevent a
      CSF leak, the optimal period of doing so has not been determined. In this study,
      the authors examined whether a longer length of stay in the hospital for the sole
      purpose of maintaining patients flat correlates with a decreased rate of CSF
      leakage. METHODS: Intraoperative and postoperative data were retrospectively
      collected in 222 cases of simple tethered cord release at 3 large children's
      hospitals. Risk factors for postoperative CSF leakage were identified. RESULTS:
      Thirty-eight patients were maintained lying flat for 24 hours, 86 for 48 hours,
      and 98 for 72 hours at the individual surgeon's discretion. A CSF leak occurred
      in 13 patients (5.9%) and pseudomeningocele developed in 9 patients (4.1%). In
      the univariate analysis, operating time, use of the microscope, use of dural
      sealant, and duration of remaining flat after surgery failed to correlate with
      the occurrence of complications. CONCLUSIONS: A longer hospital stay for
      maintaining patients flat after a simple tethered cord release appears not to
      prevent CSF leakage. However, a larger patient cohort will be needed to detect
      small differences in complication rates.

PMID- 21721887
TI  - Cavum septi pellucidi and external ventricular drain failure.

PMID- 21721888
TI  - Treatment for delayed presentation of sagittal synostosis: challenges pertaining
      to occult intracranial hypertension.
AB  - OBJECT: Patients with delayed presentation of isolated sagittal synostosis (ISS)
      pose unique surgical challenges. Intracranial hypertension can be missed in the
      absence of overt findings. Here, an algorithm is presented for the elucidation of
      intracranial hypertension and approaches to surgical treatment during calvarial
      reconstruction. METHODS: Patients with delayed presentation (age > 15 months) of
      ISS between 1997 and 2009 were identified. Symptoms, signs, and radiological
      evidence of intracranial hypertension were noted. Intraoperative management
      included calvarial reconstruction in conjunction with ventriculostomy for
      intracranial pressure (ICP) monitoring and CSF drainage in the setting of
      suspected intracranial hypertension. RESULTS: Seventeen patients underwent
      calvarial reconstruction for delayed presentation of ISS. The mean surgical age
      was 40.5 months (16.2-82.9 months), and the average follow-up was 34.2 months
      (0.6-92.2 months). Eleven patients with subtle findings of intracranial
      hypertension underwent ICP monitoring during calvarial reconstruction. The mean
      opening ICP was 23.5 cm H(2)O (16.5-29.5 cm H(2)O), and the mean closing ICP was
      7.0 cm H(2)O (3.5-17.0 cm H(2)O). Nine (81.8%) of 11 monitored patients
      demonstrated intracranial hypertension (ICP >= 20 cm H(2)O); the other 2 had
      borderline increased ICP. Perioperative morbidity was 5.9%, with 1 patient
      medically treated for transient, new-onset intracranial hypertension. The
      postoperative Whitaker category was I in 94.1% of patients, II in 5.9%, and
      III/IV in 0%. There were no reoperations or deaths. CONCLUSIONS: In this
      consecutive series, 11 of 17 patients with delayed presentation of ISS underwent
      ICP monitoring during calvarial reconstruction as a result of subtle clinical
      findings of intracranial hypertension. Nine (81.8%) of 11 monitored patients
      demonstrated intracranial hypertension. Calvarial reshaping along with ICP
      monitoring and CSF drainage facilitated reconstruction and resulted in good
      outcomes and the resolution of intracranial hypertension.

PMID- 21721889
TI  - Safety and utility of supplemental depth electrodes for localizing the ictal
      onset zone in pediatric neocortical epilepsy.
AB  - OBJECT: Depth electrodes provide a better sampling of sulci and regions of cortex
      that lie tangential to the plane of subdural electrodes. The aim of this study
      was to evaluate the utility of supplemental depth electrodes in the surgical
      treatment of pediatric patients with neocortical epilepsy. METHODS: Cases
      involving 12 consecutive pediatric patients (mean age [SD] 10.9 +/- 4.4 years)
      were reviewed. Focal resective surgery (in 9 cases) or functional hemispherectomy
      (in 3 cases) was performed after intracranial monitoring. The mean total number
      of electrodes was 118 +/- 29; the mean numbers of grid, strip, and depth
      electrodes were 95 +/- 27, 10 +/- 6, and 13 +/- 5, respectively The most common
      pathological condition was focal cortical dysplasia. RESULTS: In 4 cases, depth
      electrodes demonstrated the ictal onset zone in an area not easily accessible by
      grids or strips (in the basal temporal region in 3 cases and the upper opercular
      region in 1 case). In 3 of these 4 cases, the ictal onset zone was defined
      exclusively by the depth electrodes. In each of these 3 cases, the surface
      electrodes (on grids or strips) demonstrated early propagation but not ictal
      onset. In 9 cases, the depth electrodes also demonstrated the early propagation
      zone. The information about the ictal onset zone and the early propagation zone
      helped to provide additional information that affected the extent (in 7 cases) or
      depth (in 3 cases) of the resection. The proportion of the electrodes involved in
      resection relative to the total number of implanted electrodes was low (mean +/-
      SD, 0.26 +/- 0.09). Nine patients (75.0%) became seizure free (Engel class IA
      outcome) after surgery (mean duration of follow-up 25.7 +/- 4.29 months). There
      were no surgical complications related to intracranial electroencephalography
      monitoring. CONCLUSIONS: Most patients (75.0%) became seizure free after
      extensive monitoring and more limited resection of seizure-onset regions.
      Supplemental depth electrodes contribute to improved outcome by providing
      information about the ictal onset zone that is not accessible by grid or strip
      electrodes in some cases. The supplemental depth electrodes conferred an extra
      dimension of depth to the analysis, which allowed for successful outcome with
      more limited resection.

PMID- 21721890
TI  - Occipitocervicothoracic stabilization in pediatric patients.
AB  - OBJECT: Although rarely encountered, pediatric patients with severe cervical
      spine deformities and instability may occasionally require
      occipitocervicothoracic instrumentation and fusion. This case series reports the
      experience of 4 pediatric centers in managing this condition. Occipitocervical
      fixation is the treatment of choice for craniocervical instability that is
      symptomatic or threatens neurological function. In children, the most common
      distal fixation level with modern techniques is C-2. Treated patients maintain a
      significant amount of neck motion due to the flexibility of the subaxial cervical
      spine. Distal fixation to the thoracic spine has been reported in adult case
      series. This procedure is to be avoided due to the morbidity of complete loss of
      head and neck motion. Unfortunately, in rare cases, the pathological condition or
      highly aberrant anatomy may require occipitocervical constructs to include the
      thoracic spine. METHODS: The authors identified 13 patients who underwent
      occipitocervicothoracic fixation. Demographic, radiological, and clinical data
      were gathered through retrospective review of patient records from 4
      institutions. RESULTS: Patients ranged from 1 to 14 years of age. There were 7
      girls and 6 boys. Diagnoses included Klippel-Feil, Larsen, Morquio, and VATER
      syndromes as well as postlaminectomy kyphosis and severe skeletal dysplasia. Four
      patients were neurologically intact and 9 had myelopathy. Five children were
      treated with preoperative traction prior to instrumentation; 5 underwent both
      anterior and posterior spinal reconstruction. Two patients underwent
      instrumentation beyond the thoracic spine. Allograft was used anteriorly, and
      autologous rib grafts were used in the majority for posterior arthrodesis. Follow
      up ranged from 0 to 43 months. Computed tomography confirmed fusion in 9
      patients; the remaining patients were lost to follow-up or had not undergone
      repeat imaging at the time of writing. Patients with myelopathy either improved
      or stabilized. One child had mild postoperative unilateral upper-extremity
      weakness, and a second child died due to a tracheostomy infection. All patients
      had severe movement restriction as expected. CONCLUSIONS: Occipitocervicothoracic
      stabilization may be employed to stabilize and reconstruct complex pediatric
      spinal deformities. Neurological function can be maintained or improved. The long
      term morbidity of loss of cervical motion remains to be elucidated.

PMID- 21721891
TI  - Kyphectomy in patients with myelomeningocele treated with pedicle screw-only
      constructs: case reports and review.
AB  - OBJECT: Significant lumbar kyphosis is frequently observed in patients with
      myelomeningocele and has been associated with increasing functional impairment,
      decreased abdominal volume, respiratory impairment, discomfort, and skin
      ulcerations overlying the prominent gibbus. Treatment of severe kyphotic
      deformities can include kyphectomy, with or without ligation of the thecal sac,
      with posterior spinal fixation. However, most series have reported a high rate of
      morbidity and complications associated with surgical intervention for correction
      of kyphosis in patients with myelomeningocele. The authors describe a technique
      in which pedicle screw (PS)-only constructs are used without transection of the
      thecal sac to treat severe kyphosis successfully, with minimal morbidity.
      METHODS: The authors retrospectively reviewed medical records and radiographic
      images in 2 patients with myelomeningoceles in whom kyphectomies had been
      performed at the authors' institution between January 2007 and July 2010. They
      also reviewed the existing literature for case reports or published series of
      patients with myelomeningocele treated with kyphectomies, to evaluate the
      outcomes. RESULTS: Both patients were male and had thoracic-level
      myelomeningoceles that had been repaired at birth, with associated paraplegia.
      Neither patient had any significant scoliotic deformity associated with the
      kyphosis, and both had fixation from T-9 to the ilium, which was performed using
      PS constructs, along with L1-2 kyphectomies. The patient in Case 1 was 20 years
      old and was treated for progressive kyphosis and an ulcerated nonhealing wound
      over the gibbus. The patient in Case 2 was 10 years old and was treated for
      progressive pain and functional impairment. The 2 patients had a mean correction
      of 63%, with a mean correction of kyphotic deformity from 136 degrees  to 51
      degrees . Neither patient developed any complication in the short term
      postoperatively, whereas published series have reported high complication rates,
      including wound infection, poor wound healing, CSF leakage, pseudarthrosis, and
      shunt malfunction. CONCLUSIONS: Severe kyphotic deformities in patients with
      myelomeningocele can be safely treated using PS-only constructs without ligation
      of the thecal sac. Further evaluation with a larger sample and longer follow-up
      are needed to detect any associated complications, such as proximal junctional
      kyphosis. Further evaluation may also validate whether PS-only constructs permit
      successful outcomes with a shorter construct and fewer instrumented levels.

PMID- 21721892
TI  - Craniofacial approaches to large juvenile angiofibromas.
AB  - OBJECT: Craniofacial approaches provide excellent exposure to lesions in the
      anterior and middle cranial fossae. The authors review their experience with
      craniofacial approaches for resection of large juvenile nasopharyngeal
      angiofibromas. METHODS: Between 1992 and 2009, 22 patients (all male, mean age 15
      years, range 9-27 years) underwent 30 procedures. These cases were reviewed
      retrospectively. RESULTS: Gross-total resection of 17 (77%) of the 22 lesions was
      achieved. The average duration of hospitalization was 8.2 days (range 3-20 days).
      The rate of recurrence and/or progression was 4 (18%) of 22, with recurrences
      occurring a mean of 21 months after the first resection. All patients underwent
      preoperative embolization. Nine patients (41%) developed complications, the most
      common of which was CSF leakage (23%). The average follow-up was 27.7 months
      (range 2-144 months). The surgery-related mortality rate was 0%. Based on their
      mean preoperative (90) and postoperative (90) Karnofsky Performance Scale scores,
      100% of patients improved or remained the same. CONCLUSIONS: The authors'
      experience shows that craniofacial approaches provide an excellent avenue for the
      resection of large juvenile nasopharyngeal angiofibromas, with acceptable rates
      of morbidity and no deaths.

PMID- 21721893
TI  - Middle cerebral artery aneurysms in children: case series and review.
AB  - OBJECT: Pediatric intracranial aneurysms are rare lesions that differ from their
      adult counterparts. Aneurysms involving the middle cerebral artery (MCA) are
      particularly challenging to treat in children, as they are often fusiform and
      cannot undergo direct clipping alone. The authors recently treated a patient with
      a heavily calcified, dysplastic, left-sided MCA aneurysm. The present study was
      performed to evaluate the authors' previous operative and follow-up experience
      with these difficult lesions. METHODS: The authors performed a review of a
      prospectively maintained database of all aneurysms treated at Methodist Hospital
      in Indianapolis, Indiana, from January 1990 through November 2010. Relevant
      operative notes, clinical charts, and radiological reports were reviewed for all
      patients 18 years of age or younger. RESULTS: A total of 2949 patients with
      aneurysms were treated over the study period, including 28 children (0.95%).
      Seven children harbored MCA aneurysms. Five of these 7 aneurysms (71.4%) were
      fusiform. Two patients were treated with direct clipping, 2 underwent parent
      vessel occlusion without bypass, and 3 underwent aneurysm trapping with
      extracranial-intracranial vessel bypass. Long-term follow-up data were available
      in 6 cases. All 6 patients had a 1-year follow-up Glasgow Outcome Scale score of
      5. Long-term radiological follow-up was available in 4 patients. One patient
      required a reoperation for a recurrent aneurysm 4 years after the initial
      surgery. CONCLUSIONS: Middle cerebral artery aneurysms in children are often
      fusiform, giant, and incorporate the origins of proximal artery branches. Direct
      clipping may not be possible; trapping of the lesion may be required. Children
      seem to tolerate surgical trapping with or without bypass extremely well.
      Aggressive therapy of these rare lesions in children is warranted, as even
      patients presenting with a poor clinical grade may have excellent outcomes. Long
      term surveillance imaging is necessary because of the risk of aneurysm
      recurrence.

PMID- 21721894
TI  - Pediatric cerebellar pilomyxoid-spectrum astrocytomas.
AB  - OBJECT: Pediatric cerebellar astrocytomas with pilomyxoid features include
      classic pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid tumors (IPTs).
      Since the original description of PMA in 1999, most reports in the literature
      have described PMAs arising from the hypothalamic/chiasmatic region. To the
      authors' knowledge, PMAs arising from the posterior fossa have not been discussed
      in the neurosurgical literature. Intermediate pilomyxoid tumors, or tumors with
      pathological features of both pilocytic astrocytoma (PA) and PMA, have only
      recently been described. In this article, the authors present 2 cases that fall
      within the spectrum of pediatric cerebellar PMA-including a classic PMA and an
      intermediate pilomyxoid tumor. The authors compare the radiological presentation,
      surgical results, and postoperative course to findings in a cohort of 15 patients
      with cerebellar PAs. METHODS: Between 2003 and 2010, 2 patients with pilomyxoid
      spectrum astrocytomas underwent treatment at Vanderbilt Children's Hospital. One
      was a 22-month-old girl who presented with progressive gait disturbance and
      falls. The other was a 4-year-old girl who presented with ataxia and generalized
      weakness. In a retrospective review of pediatric cerebellar neoplasms resected by
      the senior author during this period, these tumors comprised 4% of cerebellar
      neoplasms and approximately 10% of cerebellar glial neoplasms. RESULTS: Both
      patients were treated with midline suboccipital craniotomy for resection. In both
      cases, tumor invasion anteriorly into the brainstem prevented gross-total
      resection. the patient in Case 1 was placed on chemotherapy following
      pathological diagnosis and later developed definitive evidence of leptomeningeal
      dissemination (LD) 3 years after the operation. The patient in Case 2 was placed
      on chemotherapy after exhibiting progressive evidence of local recurrence
      (findings were negative for LD) 12 months following resection. CONCLUSIONS:
      Pediatric patients with cerebellar pilomyxoid-spectrum astrocytomas appear to
      suffer higher rates of local recurrence and LD than pediatric patients with
      cerebellar PAs.

PMID- 21721895
TI  - Interpretation of magnetic resonance images in diffuse intrinsic pontine glioma:
      a survey of pediatric neurosurgeons.
AB  - OBJECT: The current management paradigm for children with newly diagnosed diffuse
      intrinsic pontine glioma (DIPG) is to establish a diagnosis and begin therapy
      based on MR imaging findings correlated with an appropriate clinical
      presentation, and without a tissue diagnosis. This strategy assumes that
      pediatric neurosurgeons and neurooncologists uniformly interpret MR imaging
      findings in this population. This study sought to examine the consistency of
      North American pediatric neurosurgeons in assessing MR images in this patient
      population, and in their surgical plans based on the interpretation of those
      images. METHODS: The authors created an online survey and invited all members of
      the American Society of Pediatric Neurosurgeons and the American Association of
      Neurological Surgeons/Congress of Neurological Surgeons Joint Section for
      Pediatric Neurosurgery to participate. The survey consisted of 58 questions, and
      48 pertained to representative MR images from 16 children who presented to The
      Children's Hospital of Colorado with diffuse pontine tumors. Based on the imaging
      presented and a standard clinical scenario, the respondent was asked if she or he
      believed a lesion to be "typical" or "atypical," whether she or he would biopsy
      the lesion, and what surgical approach would be chosen. The remaining 10
      questions pertained to respondent demographics and his or her practice regarding
      tissue preservation and interest in participating in a multicenter trial that
      included tumor biopsy in selected cases. Rates at which each lesion was
      considered to be typical or atypical and rates of recommended biopsy were
      calculated. RESULTS: Surveys were received by 269 individuals. Eighty-six
      responses were received (32.0%). No tumor was judged to be either typical or
      atypical by all respondents. Individual surgeons varied widely regarding how many
      of the tumors were judged as typical or warranted a biopsy. The percentage of
      respondents who disagreed with the majority opinion regarding whether a tumor
      qualified as typical ranged from 2.3% to 48.8%, with a median of 28.6%. More than
      75% agreement regarding whether a tumor was typical or atypical was found in 7
      (43.8%) of 16 cases. The kappa statistic regarding typicality was 0.297 +/-
      0.0004 (mean +/- SEM), implying only fair agreement. For every tumor, at least 1
      respondent who believed the lesion to be typical in appearance would nevertheless
      biopsy the lesion. Of those respondents who considered a lesion to be typical, a
      median of 5.1% (range 1.2%-66.7%) would choose to biopsy this lesion. Of those
      respondents who considered a lesion atypical, a median of 18.3% (range 3.7%-100%)
      would choose not to biopsy the lesion. Of 85 responses to the question, "Would
      you be willing to biopsy a typical diffuse pontine glioma as a part of a
      multicenter trial?," 59 (69.4%) of 85 respondents answered that they would.
      CONCLUSIONS: Although making a diagnosis based on radiographic evidence alone
      represents a well-established management paradigm for children with suspected
      DIPG, this study demonstrates considerable inconsistency on the part of pediatric
      neurosurgeons in the application of this strategy to individual patients. As
      such, the practice of diagnosing DIPG based on imaging characteristics and
      clinical history alone does not reach the appropriate threshold to be considered
      a standard of care.

PMID- 21721896
TI  - Recurrent meningitis associated with frontal sinus tuber encephalocele in a
      patient with tuberous sclerosis.
AB  - Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder that
      commonly affects the CNS. The most commonly associated brain tumors include
      cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas
      (SEGAs). The authors report an unusual case of recurrent meningitis due to a
      tuber-containing encephalocele via the posterior wall of the frontal sinus. An 11
      year-old girl presented with a history of TSC and previous SEGA resection via
      interhemispheric approach. She presented twice within 4 months with classic
      bacterial meningitis. Cerebrospinal fluid cultures revealed Streptococcus
      pneumoniae. Computed tomography and MR imaging of the brain showed a right
      frontal sinus encephalocele via a posterior frontal sinus wall defect. Both
      episodes of meningitis were treated successfully with standard regimens of
      intravenous antibiotics. The neurosurgical service was consulted to discuss
      surgical options. Via a bicoronal incision, a right basal frontal craniotomy was
      performed. A large frontal encephalocele was encountered in the frontal sinus.
      The encephalocele was herniating through a bony defect of the posterior sinus
      wall. The encephalocele was ligated and resected followed by removing frontal
      sinus mucosa and complete cranialization of frontal sinus. Repair of the sinus
      floor was conducted with fat and pericranial grafts followed by CSF diversion via
      lumbar drain. Histopathology of the resected encephalocele showed a TSC tuber
      covered with respiratory (frontal sinus) mucosa. Tuber cells were diffusely
      positive for GFAP. The patient underwent follow-up for 2 years without evidence
      of recurrent meningitis or CSF rhinorrhea. This report demonstrates that frontal
      tubers of TSC can protrude into the frontal sinus as acquired encephaloceles and
      present with recurrent meningitis. To the authors' knowledge, recurrent
      meningitis is not known to coincide with TSC. Careful clinical and radiographic
      follow-up for frontal tubers in patients with TSC is recommended.

PMID- 21721897
TI  - Intradural spinal endoscopy in children.
AB  - Intracranial endoscopy in the treatment of hydrocephalus, arachnoid cysts, or
      brain tumors has gained wide acceptance, but the use of endoscopy for intradural
      navigation in the pediatric spine has received much less attention. The aim of
      the authors' present study was to analyze their experience in using spinal
      endoscopy to treat various pathologies of the spinal canal. The authors performed
      a retrospective review of intradural spinal endoscopic cases at their
      institution. They describe 4 representative cases, including an arachnoid cyst,
      intrinsic spinal cord tumor, holocord syrinx, and split cord malformation.
      Intradural spinal endoscopy was useful in treating the aforementioned lesions. It
      resulted in a more limited laminectomy and myelotomy, and it assisted in
      identifying a residual spinal cord tumor. It was also useful in the fenestration
      of a multilevel arachnoid cyst and in confirming communication of fluid spaces in
      the setting of a complex holocord syrinx. Endoscopy aided in the visualization of
      the spinal cord to ensure the absence of tethering in the case of a long-length
      Type II split spinal cord malformation. Conclusions Based on their experience,
      the authors found intradural endoscopy to be a useful surgical adjunct and one
      that helped to decrease morbidity through reduced laminectomy and myelotomy. With
      advances in technology, the authors believe that intradural endoscopy will begin
      to be used by more neurosurgeons for treating diseases of this anatomical region.

PMID- 21721898
TI  - Endoscopic third ventriculostomy.

PMID- 21721899
TI  - "Swing-ding"?

PMID- 21721901
TI  - In vitro exposure of Nile tilapia (Oreochromis niloticus) testis to estrogenic
      endocrine disrupting chemicals: mRNA expression of genes encoding steroidogenic
      enzymes.
AB  - Many environmental pollutants can exert adverse effects on exposed organisms,
      including fish, leading to disruption of the endocrine system. Enzymes involved
      in the sex steroid biosynthesis are potential targets for the toxic action of
      pollutants. In this context, we investigated the hypothesis that selected
      estrogenic chemicals-the pharmaceutical estrogen ethinylestradiol (EE2), the
      phytoestrogen genistein (GEN), and the industrial compound bisphenol A (BPA)-may
      cause endocrine disruption by directly disturbing steps of fish steroidogenic
      pathways. We studied the mRNA expression of eight selected genes encoding
      steroidogenic enzymes (11beta-HSD2, 20beta-HSD, 3beta-HSD1, 17beta-HSD1, 17beta
      HSD8, 17beta-HSD12, CYP19a, CYP19b) by quantitative real-time PCR. Testis slices
      from adult specimens of the model fish Nile tilapia were exposed in vitro for 3
      and 8 h either to individual or to mixture solutions of EE2 (100 ng/L), GEN (200
      ng/L), and BPA (10 ug/L); all at the peak concentrations observed in the Douro
      River estuary (Portugal). Our data revealed that only the mixture of the tested
      chemicals directly induced the expression of 11beta-HSD2, 17beta-HSD1, and 17beta
      HSD12, after 8 h, whereas no effect was seen for chemicals tested individually.
      The gene expression pattern agrees with the concept of dose addition for
      environmental mixtures, and for the first time an interference of estrogenic EDCs
      is reported for 17beta-HSD1 and 17beta-HSD12.

PMID- 21721902
TI  - Spatial and temporal patterns of intraspecific morphological variation in
      Dactylogyrus simplexus from fathead minnows in Nebraska.
AB  - Dactylogyrus simplexus Monaco and Mizelle, 1955, occurs on the gills of fathead
      minnows (Pimephales promelas). Previous research on parasites of fathead minnows
      from 3 converging Nebraska streams, Elk Creek, Oak Creek, and West Oak Creek,
      shows that fish in each stream constitute distinct populations. To determine
      whether their parasites had diverged structurally in response to such isolation,
      or in response to seasonal change, we searched for patterns of intraspecific
      morphometric variation among D. simplexus. Over 3 collection dates in fall 2007,
      spring 2008, and fall 2009, 203 D. simplexus were collected from Elk and West Oak
      Creeks. We ran 1-way ANOVA to compare differences in 15 distinct point-to-point
      measurements of sclerotized parts across sites and collection dates. Significant
      differences were found in some D. simplexus measurements between Elk and West Oak
      Creeks for all 3 collection dates, but the characteristics that differed and the
      trend of variation between the creeks were not consistent over time. Dactylogyrus
      simplexus from both Elk and West Oak Creeks showed consistent patterns of
      variation over time for 5 measurements, including hamulus gap width, bar length,
      marginal hook length, sickle length, and sickle width. In conclusion, D.
      simplexus demonstrate consistent patterns of seasonal variation, but not spatial.

PMID- 21721903
TI  - Redescription of Corallobothrium solidum (Cestoda: Proteocephalidea) and erection
      of a new genus, Essexiella, for tapeworms from channel catfishes (Ictaluridae).
AB  - The proteocephalidean tapeworm, Corallobothrium solidum, type species of the
      genus, is redescribed on the basis of the examination of its type specimens and
      extensive material recently collected from Malapterurus electricus (type host).
      Some morphological characteristics of taxonomic importance are reported for the
      first time, such as the presence of semispherical (U-shaped) sphincters on the
      external (outer) margin of the suckers, a vaginal sphincter, a well-developed
      seminal receptacle, and a unique morphology of the eggs. Corallobothrium solidum
      differs from the 2 remaining species of the genus, both parasitic in channel
      catfishes (Ictaluridae), in its scolex shape, morphology of its suckers, presence
      of longitudinal and transverse grooves on the body surface, dense network of
      excretory canals in the apical part of the scolex, morphology of the eggs, and
      uterine development. The non-monophyletic nature of Corallobothrium is further
      supported by molecular data (partial sequences of the 28S rRNA gene) because C.
      solidum and the 2 remaining species from ictalurids do not form a monophyletic
      assemblage. Therefore, Essexiella n. gen. is proposed to accommodate Essexiella
      fimbriatum new comb. (type and only species; syn. Corallobothrium fimbriatum)
      from channel catfish. Essexiella n. gen. differs from Corallobothrium,
      Megathylacoides, and Megathylacus by the absence of a sphincter in the suckers,
      from Corallotaenia by the shape of the scolex and the number and shape of
      proglottids, and from Paraproteocephalus by the structure of the uterus. The
      diagnosis of Corallobothrium, which becomes monotypic and restricted to electric
      catfishes in Africa, is emended. The remaining species of Corallobothrium,
      Corallobothrium parafimbriatum, is tentatively transferred to Corallotaenia as
      Corallotaenia parafimbriata n. comb., based on molecular data, small size of the
      strobila, and shape of the scolex.

PMID- 21721904
TI  - Genetic characterization of Toxoplasma gondii isolates from pigs in southwestern
      China.
AB  - The genetic diversity of Toxoplasma gondii varies in different geographical
      regions. Isolates of T. gondii in South America, for example, are genetically and
      biologically divergent from those in North America and Europe, where the
      population structure is highly clonal and composed mainly of 3 distinct lineages,
      i.e., Types I, II, and III. However, little is known of the T. gondii genotypes
      in the People's Republic of China. Toxoplasma gondii infection in pigs causes
      significant economic loss and presents a risk for human infection. We conducted a
      survey to determine the genetic diversity of this parasite in slaughtered pigs
      from Yunnan Province, southwestern China. In total, 412 DNA samples were
      extracted from hilar lymph nodes and livers of pigs from slaughterhouses in
      Yunnan Province in southwest China, 56 of which were found to be positive for the
      T. gondii SAG3 gene. These positive DNA samples were typed at 10 genetic markers,
      including 9 nuclear loci, i.e., SAG1, SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8,
      c29-2, and an apicoplast locus Apico. Of these, 5 isolates were genotyped with
      complete data for all loci. Only 1 genotype (ToxoDB 9) was identified, previously
      reported as a widespread lineage from pigs, cats, and human patients in China.
      The results indicate that this genotype may be the major T. gondii lineage in
      China and possibly all of eastern Asia. This is the first report of genetic
      typing of T. gondii isolates from pigs in China's southwestern Yunnan Province,
      the results of which have implications for the prevention and control of T.
      gondii infections in humans and other animals.

PMID- 21721906
TI  - Carbon tetrachloride: a hepatotoxin causes oxidative stress in murine peritoneal
      macrophage and peripheral blood lymphocyte cells.
AB  - CONTEXT: Carbon tetrachloride (CCl4) is frequently used as a chemical inducer of
      tissue damage. Their effects on mouse peritoneal macrophages and also in
      peripheral blood lymphocytes are still unknown. OBJECTIVE: Therefore we tried to
      focus on intracellular oxidative stress produced by CCl4 in mouse macrophage and
      lymphocyte cells. METHODS: Intraperitoneal administration of CCl4 induces
      intracellular superoxide anions production in mouse macrophages and peripheral
      blood lymphocytes and leads a subsequent lipid peroxidation and protein
      oxidation. N-acetyl cystein (NAC) and vitamin C were administered
      intraperitoneally at a dose of 150 mg/kg and their effect on demodulating the
      oxidative stress is also checked. RESULT AND DISCUSSION: Several in vitro
      approaches have already been established as a free radical scavenging models, but
      this free radical screening models is not always correlated with the in vivo
      screening models. NAC and vitamin C were administered intraperitoneally and
      significant reduction of the oxidative stress in term of scavenging of toxic
      superoxide anion observed in both the macrophages and lymphocytes. CONCLUSION:
      Therefore we are hopeful that our work will light a new insight into the
      screening of in vivo free radical scavenging model for evaluating anti
      inflammatory compounds.

PMID- 21721907
TI  - Can alpha-synuclein be targeted in novel therapies for Parkinson's disease?

PMID- 21721909
TI  - Pramipexole for the treatment of early Parkinson's disease.
AB  - Pramipexole is a nonergolinic dopamine agonist, with high affinity for the D2
      subfamily of dopamine receptors. Pramipexole is efficacious for the symptomatic
      treatment of early Parkinson's Disease (PD) and its early use, before that of
      levodopa can delay the emergence of levodopa-related motor complication. Dosage
      should be increased gradually from a starting dose of 0.375 mg/day up to a
      maximum of 4.5 mg/day in equally divided doses taken three times per day with
      pramipexole immediate-release or equivalent daily dosages once-daily with
      pramipexole extended-release. Pramipexole can also improve depressive symptoms
      and possibly health-related quality of life in PD. Nonetheless, its use is not
      devoid of tolerability problems. While peripheral adverse drug reactions, such as
      nausea, vomiting or orthostatic hypotension, can be effectively treated and
      usually pose few problems to most patients, neuropsychiatric events can seriously
      limit the use of pramipexole in some cases. Indeed, excessive daytime somnolence,
      impulse-control disorders, hallucinations or delusions can severely affect
      patients, causing important personal or social handicap. Patients should be
      informed about the risk of such neuropsychiatric complications and their presence
      should be actively detected at each consultation. More effort will have to be put
      into further studying the risk-benefit ratio of pramipexole and other dopamine
      agonists in the treatment of early PD.

PMID- 21721910
TI  - Genome-wide investigation of rare structural variants identifies VIPR2 as a new
      candidate gene for schizophrenia.
AB  - Research has shown that structural variation in the human genome, including rare
      copy number variations (CNVs), contributes to genetic susceptibility to
      psychiatric diseases, such as schizophrenia, a devastating complex disorder with
      a high genetic load. The study by Vacic et al. applied a genome-wide approach to
      detect novel, rare and highly penetrant CNVs. Detailed analysis of
      microduplications at 7q36.3 revealed that the neuropeptide receptor gene VIPR2
      confers a significant risk for schizophrenia. This suggests that altered
      vasoactive intestinal signaling contributes to the genetic etiology of this
      disorder. This article recapitulates the findings of this study within the
      context of current knowledge of CNVs in the field of psychiatric disease.

PMID- 21721911
TI  - Brain tissue changes and antipsychotic medication.
AB  - Schizophrenia is associated with progressive brain changes, including progressive
      brain tissue decreases and lateral ventricular volume increases for up to at
      least 20 years after disease onset. In view of the fact that the vast majority of
      such patients are treated with antipsychotic medication and that recent non-human
      mammalian studies have reported an association between antipsychotic medication
      and brain tissue changes, the important question arises as to whether the brain
      changes seen in schizophrenia are associated with antipsychotic medication. The
      reviewed article presents structural magnetic resonance neuroimaging data
      relating to 211 patients with schizophrenia from the Iowa Longitudinal Study,
      which demonstrates that greater intensity of antipsychotic treatment was
      associated with indicators of generalized and specific brain tissue changes,
      after controlling for the effects of illness duration, illness severity and
      substance abuse. The study and its implications are discussed in the context of
      the current state of knowledge regarding the pathophysiology of schizophrenia.

PMID- 21721912
TI  - Neuropathological correlates of late-life depression.
AB  - The relationship between depression and both dementia and cerebrovascular
      pathology has, for good reason, received much attention from researchers and
      clinicians alike. Over previous decades, several generations of hypotheses have
      linked depression to the etiology or pathophysiology of dementia. Similarly, a
      host of studies have looked at the interplay between cerebrovascular pathology
      and late-life depression. This has resulted in new concepts of late-life
      depression, such as vascular depression. The study under evaluation sought to
      assess the neuropathological correlates of late-life depression by examining
      brains donated for study by a large sample of participants in the Medical
      Research Council Cognitive Function and Ageing Study. The study is unique in its
      large size, representative sample of participants and rigorous exclusion of
      participants who were demented during their life, using structured interviews to
      diagnose depression at multiple life stages before death. The results suggest
      that depression is not associated with cortical pathology of either Alzheimer's
      dementia or cerebrovascular disease. There were associations with Lewy body
      pathology and loss of neurons in the hippocampus and other subcortical areas.
      Although the authors are cautious with regard to drawing firm conclusions, the
      results suggest that, in the community, depression is not an important
      etiological factor for the development of the neuropathology of Alzheimer's
      disease and there was no association with cerebrovascular pathology. Although
      restricted to only very few subjects, the association with Lewy body pathology
      warrants further research, as does the association with neuronal loss in the
      hippocampus.

PMID- 21721913
TI  - Sexual dimorphism in schizophrenia: is there a need for gender-based protocols?
AB  - Gender differences have been reported in various aspects of schizophrenia,
      including its epidemiology, clinical course and the response to antipsychotic
      medications. Over the past few years the authors have been investigating sex
      differences in brain function in individuals with schizophrenia and have found an
      intriguing disturbance of normal sexual dimorphism during emotional and cognitive
      processing. These results can be partly accounted for by altered levels of sex
      steroid hormones (i.e., estrogen and testosterone) in patients. A handful of
      clinical research groups have tried low doses of estrogen, testosterone or their
      precursors as adjunct therapies to the currently available antipsychotic
      medications in women and men with schizophrenia. The results have been promising,
      but further investigation is warranted. In the future, new more specific
      steroidal compounds will be developed and we will see more studies examining sex
      differences in the brain, behavior and mental health problems. This research will
      help to identify individuals who may benefit greatest from adjunct hormonal
      therapies and will further our understanding of the etiology of schizophrenia and
      other psychiatric disorders.

PMID- 21721914
TI  - Chronobiological therapy for mood disorders.
AB  - Alteration of the sleep-wake cycle and of the sleep structure are core symptoms
      of a major depressive episode, and occur both in course of bipolar disorder and
      of major depressive disorder. Many other circadian rhythms, such as the daily
      profiles of body temperature, cortisol, thyrotropin, prolactin, growth hormone,
      melatonin and excretion of various metabolites in the urine, are disrupted in
      depressed patients, both unipolar and bipolar individuals. These disrupted
      rhythms seem to return to normality with patient recovery. Research on circadian
      rhythms and sleep have led to the definition of nonpharmacological therapies of
      mood disorder that can be used in everyday practice. These strategies, named
      chronotherapeutics, are based on controlled exposures to environmental stimuli
      that act on biological rhythms, and demonstrate good efficacy in the treatment of
      illness episodes. They include manipulations of the sleep-wake rhythm (such as
      partial and total sleep deprivation, and sleep phase advance) and of the exposure
      to the light-dark cycle (light therapy and dark therapy). In recent years, an
      increasing literature about the safety and efficacy of chronobiological
      treatments in everyday psychiatric settings has supported the inclusion of these
      techniques among the first-line antidepressant strategies for patients affected
      by mood disorders.

PMID- 21721915
TI  - Understanding aberrant white matter development in schizophrenia: an avenue for
      therapy?
AB  - Although historically gray matter changes have been the focus of
      neuropathological and neuroradiological studies in schizophrenia, in recent years
      an increasing body of research has implicated white matter structures and its
      constituent components (axons, their myelin sheaths and supporting
      oligodendrocytes). This article summarizes this body of literature, examining
      neuropathological, neurogenetic and neuroradiological evidence for white matter
      pathology in schizophrenia. We then look at the possible role that antipsychotic
      medication may play in these studies, examining both its role as a potential
      confounder in studies examining neuronal density and brain volume, but also the
      possible role that these medications may play in promoting myelination through
      their effects on oligodendrocytes. Finally, the role of potential novel therapies
      is discussed.

PMID- 21721916
TI  - Unmet treatment needs in schizophrenia patients: is asenapine a potential
      therapeutic option?
AB  - Adverse metabolic events, such as increased adiposity, hyperglycemia, diabetes
      mellitus and dyslipidemia, have been associated with treatment using atypical
      antipsychotic medications. However, the complexity of some of the reports on this
      problem and marketing efforts in this area may make it difficult for
      psychiatrists to remain fully and accurately informed about the metabolic
      complications of atypical antipsychotic therapy. Little is currently known about
      how psychiatrists view what they have read or heard, how they perceive the
      available information and how this affects their management of patients with
      schizophrenia. A number of studies have demonstrated that nonadherence to the
      medication regimen in schizophrenia is associated with poor symptomatic outcome,
      increased risk of relapse, more frequent use of compulsory treatment and
      increased risk of suicide and severe self-harm. Suicide is a major cause of death
      among schizophrenic patients, and their attitude toward medication can make the
      difference between a proper therapeutic regimen that protects patients from
      suicide risk versus discontinuation of treatments that are associated with
      disabling symptoms, some of which are risk factors for suicide. We review the
      characteristics of a new drug, asenapine, that may improve adherence in patients
      as a result of a distinctive receptor profile that may be associated with fewer
      side effects than other second-generation antipsychotic drugs.

PMID- 21721917
TI  - Insights into hallucinations in schizophrenia: novel treatment approaches.
AB  - Novel strategies are needed in the treatment of hallucinations as a subgroup of
      patients with pathological hallucinations (>30%) do not respond to antipsychotics
      or are not compliant with medication. We review recently developed biological and
      cognitive treatments. Repetitive transcranial magnetic stimulation concerns
      neuromodulation targeted at aberrant activity in regions shown to be hyperactive
      in neuroimaging studies. Repetitive transcranial magnetic stimulation has been
      shown to reduce auditory hallucinations in several studies. However, not all
      studies have confirmed such effects, and a number of questions remain. With
      regard to cognitive therapeutic approaches, new proposals include attention
      training, acceptance and commitment therapy, and competitive memory training.
      After a brief discussion of these approaches, we take stock of recent advances
      and discuss avenues for future research.

PMID- 21721918
TI  - Insulin dysfunction and allostatic load in bipolar disorder.
AB  - Bipolar disorder (BD) is associated with substantial morbidity, as well as
      premature mortality. Available evidence indicates that 'stress-sensitive' chronic
      medical disorders, such as cardiovascular disease, obesity and Type 2 diabetes
      mellitus, are critical mediators and/or moderators of BD. Changes in physiologic
      systems implicated in allostasis have been proposed to impact brain structures
      and neurocognition, as well as medical comorbidity in this population. For
      example, abnormalities in insulin physiology, for example, insulin resistance,
      hyperinsulinemia and central insulinopenia, are implicated as effectors of
      allostatic load in BD. Insulin's critical role in CNS physiological (e.g.,
      neurotrophism and synaptic plasticity) and pathophysiological (e.g.,
      neurocognitive deficits, pro-apoptosis and amyloid deposition) processes is amply
      documented. This article introduces the concept that insulin is a mediator of
      allostatic load in the BD and possibly a therapeutic target.

PMID- 21721919
TI  - Therapeutic use of omega-3 fatty acids in bipolar disorder.
AB  - Bipolar disorder (BD) is a severe, chronic affective disorder, associated with
      significant disability, morbidity and premature mortality. Omega-3
      polyunsaturated fatty acids (PUFAs) play several important roles in brain
      development and functioning. Evidence from animal models of dietary omega-3 (n-3)
      PUFA deficiency suggest that these fatty acids are relevant to promote brain
      development and to regulate behavioral and neurochemical aspects related to mood
      disorders, such as stress responses, depression and aggression, as well as
      dopaminergic content and function. Preclinical and clinical evidence suggests
      roles for PUFAs in BD. n-3 PUFAs seem to be an effective adjunctive treatment for
      unipolar and bipolar depression, but further large-scale, well-controlled trials
      are needed to examine its clinical utility in BD. The use of n-3 as a mood
      stabilizer among BD patients is discussed here. This article summarizes the
      molecular pathways related to the role of n-3 as a neuroprotective and neurogenic
      agent, with a specific focus on BDNF. It is proposed that the n-3-BDNF
      association is involved in the pathophysiology of BD and represents a promising
      target for developing a novel class of rationally devised therapies.

PMID- 21721920
TI  - Complementary and alternative medicine therapies in mood disorders.
AB  - This article reviews the potential uses of complementary and alternative medicine
      (CAM) techniques for individuals with mood disorders. Mood disorders are among
      the most prevalent mental health issues today and there are many approaches
      towards their management. While many different types of medication are available,
      more and more people turn to CAM interventions to help manage their mood
      disorders. CAM interventions can include herbal remedies, acupuncture and
      meditation. There is an increasing number of research studies on CAM intervention
      in mood disorders, and this article critiques such data and attempts to provide a
      clinical perspective within which these CAM interventions might be considered.

PMID- 21721923
TI  - Evaluation of the skin sensitization potential of chemicals in THP-1/keratinocyte
      co-cultures.
AB  - Many attempts have been made to develop in vitro sensitization tests that employ
      dendritic cells (DCs), DC-like cell lines or keratinocytes. The aim of the
      present investigation was to establish a co-culture of THP-1 cells and
      keratinocytes for evaluation of skin sensitization potential of chemicals. Co
      cultures were constructed by THP-1 cells cultured in lower compartments and
      keratinocytes cultured in upper compartments of cell culture inserts. After 24 h
      exposure to sensitizers (2, 4-dinitrochlorobenzene, p-phenylenediamine,
      formaldehyde, nickel sulfate, isoeugenol and eugenol) and non-sensitizers (sodium
      lauryl sulfate, benzalkonium chloride and lactic acid), the expression of CD86
      and CD54 on THP-1 cells were evaluated by flow cytometry, and cell viabilities
      were determined. The sensitizers induced the augmentation of CD86 and CD54
      expression, but the non-sensitizers had no significant effect. Compared with mono
      cultures of THP-1 cells, the augmentation of CD86 and CD54 could be detected even
      at a non-toxic concentration of sensitizers in THP-1 cell/keratinocyte co
      cultures. Moreover, isoeugenol was distinguished as a sensitizer in co-cultures,
      but failed to be identified in mono-cultures. These results revealed that the co
      cultures of THP-1 cells and keratinocytes were successfully established and
      suitable for identifying sensitizers using CD86 and CD54 expression as
      identification markers.

PMID- 21721924
TI  - Comparison of point-of-care testing glucose results from intensive care patients
      measured with network-ready devices.
AB  - BACKGROUND: Fast and reliable glycemic control is of tremendous importance in
      intensive care units. Point-of-care devices used in professional care have to be
      precise and of low variability, and their connectivity has to outrange the
      abilities of home-care equivalents. In particular, the meter's efficiency should
      be tested not only with spiked blood samples from healthy donors but also with
      blood from intensive care unit patients because of their special matrix
      conditions as low hematocrit, oxygen pressure variability, or medication.
      METHODS: Four types of network-ready glucose meters were tested. Data, obtained
      from native or maltose/xylose-spiked intensive care patients' blood, were
      compared (oxygen, hematocrit, glucose, and maltose and xylose dependencies) with
      those from a YSI 2300 STAT PlusTM glucose and lactate analyzer (YSI Life
      Sciences, Yellow Springs, OH). According to ISO 15197 (2003) acceptance of
      glucose meter results was determined. Quality control results were investigated
      considering a new calculation type in German guidelines. RESULTS: Three of the
      meters fulfill the overall acceptance criterions. Two of the meters achieved
      accuracies above 93% in all oxygen, hematocrit, and glucose subgroups. Maltose
      generates deviations leading to accuracies from 71.1% to 100%, and xylose causes
      accuracies of 33.3% to 100%. CONCLUSIONS: State of the art for manufacturing
      small network point-of-care testing glucose meters has reached a new level of
      precision, but the devices still have to be handled with care, and in particular
      the staff of an intensive care unit still needs knowledge about possible
      interferences.

PMID- 21721921
TI  - The interplay between gait, falls and cognition: can cognitive therapy reduce
      fall risk?
AB  - In this article, we briefly summarize the incidence and significant consequences
      of falls among older adults, the insufficient effectiveness of commonly used
      multifactorial interventions and the evidence linking falls and cognitive
      function. Recent pharmacologic and nonpharmacologic studies that evaluated the
      effects of cognitive therapy on fall risk are reviewed. The results of this
      article illustrate the potential utility of multiple, diverse forms of cognitive
      therapy for reducing fall risk. The article also indicates that large-scale,
      randomized controlled trials are warranted and that additional research is needed
      to better understand the pathophysiologic mechanisms underlying the interplay
      between human mobility, fall risk and cognitive function. Nonetheless, we suggest
      that multimodality interventions that combine motor and cognitive therapy should,
      eventually, be incorporated into clinical practice to enable older adults and
      patients to move safer and with a reduced fall risk.

PMID- 21721925
TI  - Acupuncture for symptom management in hemodialysis patients: a prospective,
      observational pilot study.
AB  - OBJECTIVES: Patients undergoing hemodialysis suffer from a variety of
      complications related to end-stage renal disease. This prospective, observational
      pilot study aims to determine the feasibility, safety, and possible benefits of
      acupuncture for symptom management in patients undergoing hemodialysis. METHODS:
      Twenty-four (24) patients undergoing hemodialysis received acupuncture treatment
      for their symptoms. Manually stimulated, individualized acupuncture treatments
      were provided twice a week for 6 consecutive weeks on a nondialysis day or on the
      day of hemodialysis prior to initiating treatment. Symptoms were evaluated using
      the Measure Your Medical Outcome Profiles 2 questionnaire, and quality of life
      was measured by Kidney Disease Quality of Life-Short Form (KDQOL-SF(TM)) Version
      1.3 at baseline, 7 weeks and 11 weeks from baseline. Statistical analysis was
      conducted on the basis of the intention-to-treat principle. RESULTS: Twenty-one
      (21) patients (87%) completed the whole treatment course and follow-up
      evaluation. Three (3) patients dropped out due to increased fatigue (n = 1),
      pancreatic and renal transplantation (n = 1), and infections of the arteriovenous
      fistula used for hemodialysis access (n = 1). Patients experienced a significant
      improvement of symptoms considered the most bothersome, reporting a decrease of
      1.87 and 2.08 points on a 0-6 symptom scale at 7 weeks and 11 weeks, respectively
      (both p < 0.0001). Some subscales of KDQOL-SF(TM) showed significant improvement
      at 7 weeks (effects of kidney disease, burden of kidney disease, role-limitations
      physical, emotional well-being, and energy/fatigue) and 11 weeks (physical
      functioning and energy/fatigue). No serious adverse events related to acupuncture
      occurred. CONCLUSIONS: Acupuncture seems feasible and safe for symptom management
      in patients undergoing hemodialysis. Future controlled trials are needed to
      confirm the benefits of acupuncture.

PMID- 21721926
TI  - What to wear when practicing oriental medicine: patients' preferences for
      doctors' attire.
AB  - OBJECTIVES: The patient's impression of the doctor is an important factor in a
      clinical consultation, and the doctor's attire also plays a great role in
      promoting trust and confidence in the patients. Previous studies have shown that
      a doctor in a white coat will appear more professional, confident, and
      trustworthy. The objective of this study was to investigate whether the influence
      of a doctor's attire applies for both Western and Oriental medical doctors.
      METHODS: Before a clinical consultation, 153 patients were asked to assess
      photographs showing an identical doctor wearing four different dress styles. The
      patients were divided into two groups: One group was told that the doctor in the
      photograph was a Western doctor, whereas the other group was told that the doctor
      was an Oriental medical doctor. Patients' ratings of preference for competency,
      trustworthiness, comfortableness, and treatment choice were then measured and
      compared. RESULTS: Patients preferred a doctor in a white coat the most, giving
      highest ratings for competency and trustworthiness, while reporting to feel most
      comfortable with a doctor in traditional dress. No difference was found between
      Western and Oriental medical doctors. Patients prefer their doctors to wear white
      coats, regardless of whether the doctor is a Western or Oriental medical doctor,
      even though patients feel more comfortable with doctors wearing traditional
      dress. CONCLUSIONS: The preference about doctors' attire symbolizes the
      perception of patients regarding their doctor's image. Taking the historical and
      symbolic meaning of the doctor's white coat together, this clear preference of
      patients for the white coat might imply that patients require a more scientific
      and professional image, regardless of whether the doctors are Western or Oriental
      medical doctors.

PMID- 21721927
TI  - Differentiation of human LAN-5 neuroblastoma cells induced by extremely low
      frequency electronically transmitted retinoic acid.
AB  - BACKGROUND: Jaques Benveniste suggested that electronic transmission of 4-phorbol
      12-b-myristate-13-acetate (PMA) activity, carried out using a simple amplifier
      configured to function as an oscillator when coupled to two electromagnetic
      coils, demonstrates the same chemical activity as the active molecule. The
      results obtained suggested that there are associated signals at the PMA molecules
      that can be transferred to target neutrophils by artificial physical means in a
      fashion that mimics the original molecules. METHODS: Retinoic acid was placed at
      room temperature on one coil attached to an oscillator (VEGA select 719), while
      LAN-5 neuroblastoma cells were placed on another coil and incubated under
      controlled condition. The oscillator was then turned on for 12 hours a day for 5
      days, after which cells were counted and morphology studied by contrast
      microscopy. RESULTS: The effect of the differentiating agent added to the cell
      culture by physical means generates a decrease in cell growth, metabolic
      activity, and the protrusion of a neuritelike structure typical of the
      differentiated cells. CONCLUSIONS: These preliminary results suggest that
      retinoic acid molecules emit signals that can be transferred to LAN-5
      neuroblastoma cells by artificial physical means in a manner that seems related
      to the chemical structure of the source molecules.

PMID- 21721928
TI  - Delivering happiness: translating positive psychology intervention research for
      treating major and minor depressive disorders.
AB  - Despite the availability of many treatment options, depressive disorders remain a
      global public health problem. Even in affluent nations, 70% of reported cases
      either do not receive the recommended level of treatment or do not get treated at
      all, and this percentage does not reflect cases of depression that go unreported
      due to lack of access to health care, stigma, or other reasons. In developing
      countries, the World Health Organization estimates that <10% receive proper
      depression care due to poverty, stigma, and lack of governmental mental health
      resources and providers. Current treatments do not work for everyone, and even
      people who achieve remission face a high risk of recurrence and residual
      disability. The development of low-cost effective interventions that can serve
      either as initial therapy for mild symptoms or as adjunctive therapy for partial
      responders to medication is an immense unmet need. Positive activity
      interventions (PAIs) teach individuals ways to increase their positive thinking,
      positive affect, and positive behaviors. The majority of such interventions,
      which have obtained medium-size effect sizes, have been conducted with
      nondepressed individuals, but two randomized controlled studies in patients with
      mild clinical depression have reported promising initial findings. In this
      article, the authors review the relevant literature on the effectiveness of
      various types of PAIs, draw on social psychology, affective neuroscience and
      psychophamacology research to propose neural models for how PAIs might relieve
      depression, and discuss the steps needed to translate the potential promise of
      PAIs as clinical treatments for individuals with major and minor depressive
      disorders.

PMID- 21721929
TI  - Dissecting the requirements for maintenance of the CMV-specific memory T-cell
      pool.
AB  - Cytomegalovirus (CMV) infection promotes a broad T-cell response, with the
      resulting memory cells displaying diverse phenotypes. CMV establishes lifelong
      persistence/latency, and it is thought that viral antigens expressed during this
      period may regulate the expansion and/or maintenance of "inflationary" CD8 T
      memory populations that display an effector memory phenotype. We show here that
      mouse CMV (MCMV)-specific inflationary memory T cells do not decrease in number
      after thymectomy, indicating that recent thymic emigrants are not strictly
      required for their maintenance. Furthermore, persistent MCMV replication in the
      salivary gland does not significantly impact the T-cell memory compartment, as
      surgical removal did not alter its composition. These results shed light upon the
      mechanisms required for maintenance of the large, MCMV-specific T-cell memory
      pool.

PMID- 21721930
TI  - Protein A-based ELISA: its evaluation in the diagnosis of herpes simplex
      encephalitis.
AB  - Herpes simplex encephalitis (HSE) represents one of the most severe infectious
      diseases of the central nervous system. As effective antiviral drugs are
      available, early rapid and reliable diagnosis has become important. The objective
      of the present study was to develop a sensitive enzyme-linked immunosorbent assay
      (ELISA) protocol for herpes simplex virus (HSV) antigen detection by assessing
      the usefulness of hyperimmune sera isolated from HSV-seropositive patients. A
      total of 52 cerebrospinal fluid (CSF) and 62 serum samples of HSE patients and
      non-HSE persons were analyzed. An in-house ELISA protocol utilizing hyperimmune
      sera was developed for HSV antigen detection. To improve the specificity of the
      method, protein A was incorporated into the protocol for ELISA. The sensitivity
      (70% and 90%) of antigen detection was high in CSF and serum samples,
      respectively, of confirmed HSE patients. However, lower specificity (52.3% and
      42.3%), respectively, was obtained, which was improved by using protein A in the
      ELISA protocol. The modification in the method yielded good sensitivity (80% and
      70%) and specificity (85.7% and 88.4%) of HSV antigen detection in the CSF and
      sera, respectively, of the HSE and non-HSE groups. The ELISA method utilizing
      hyperimmune sera along with protein A for HSV antigen detection yielded good
      sensitivity and specificity in both CSF and sera, and hence can be useful for the
      diagnosis of HSE.

PMID- 21721931
TI  - The ratio of Th-17 to Treg cells is associated with survival of patients with
      acute-on-chronic hepatitis B liver failure.
AB  - Both T-helper 17 cells (Th-17) and CD4(+)CD25(+) regulatory T cells (Tregs) play
      important roles in the pathogenesis of hepatitis B virus (HBV) infection. Recent
      studies have suggested that Th-17 and Treg cells are increased in patients with
      chronic hepatitis B (CHB). This study further characterizes Th-17 and Treg cells
      in the blood of HBV-associated acute-on-chronic liver failure (ACLF) patients,
      and aids our understanding of how the two subsets of CD4(+) T cells affect each
      other and contribute to survival. Blood samples were obtained from 30 patients
      with HBV-associated ACLF, 30 patients with CHB, and 30 normal controls (NC). The
      frequencies of Th-17 and Treg cells were determined by intracellular cytokine
      staining analysis. To observe the suppressive function of Tregs, purified
      CD4(+)CD25(+) Tregs from peripheral blood mononuclear cells (PBMCs) were co
      cultured with CD4(+)CD25(-) T cells for 48 h, and then IFN-gamma and IL-17A from
      the supernatants were measured by ELISA. We found that both Th-17 and FoxP3(+)
      Treg cells were increased in ACLF patients. IL-17A secretion by CD4(+) T cells
      was not regulated by Treg cells, even though Tregs exhibited significant
      inhibition of IFN-gamma production. Most importantly, the ratio of Th-17 to Treg
      cells was associated inversely with the survival of ACLF patients. These findings
      provide new information regarding the pathogenesis of HBV-associated ACLF, and
      the ratio of Th-17 to Tregs may represent a potential prognostic marker for the
      disease.

PMID- 21721932
TI  - The presence of functionally relevant toll-like receptor polymorphisms does not
      significantly correlate with development or outcome of sepsis.
AB  - AIMS: Members of the toll-like receptor (TLR) family have been shown to play
      important roles in inflammatory responses. Single-nucleotide polymorphisms (SNPs)
      altering receptor activity may either have detectable effects or might be without
      results due to compensatory mechanisms. We determined the genotype frequencies of
      functionally relevant SNPs in TLR2, 4 and 5 in critically ill patients (n=150)
      from a multidisciplinary surgical intensive care unit (ICU). The inflammatory
      response (procalcitonin, C-reactive protein, white blood count) and clinical
      classification (Acute Physiology and Chronic Health Evaluation Score II,
      Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment)
      were monitored daily. RESULTS: The genetic polymorphisms correlate with neither
      development nor outcome of sepsis. No correlations were found between C-reactive
      protein or WBC and the investigated SNPs. In patients in the ICU with abdominal
      surgery and multiple trauma, the TLR2-R753Q SNP was associated with infection at
      ICU admission (p<0.01); and for carriers of the TLR4-D299G SNP, a trend was
      observed (p=0.0776). Patients with multiple trauma carrying the TLR4-D299G SNP
      displayed significantly higher levels of procalcitonin (p=0.0212). CONCLUSIONS:
      None of the investigated SNPs clearly predicted outcome of sepsis-related
      multiorgan failure. TLR2-R753Q SNP may be a useful marker to identify patients
      with high risk to develop infections at ICU admission but should be validated in
      larger studies. Future SNP-arrays investigating predisposition for infection
      should include this SNP alone or in combination with other functionally relevant
      SNPs.

PMID- 21721933
TI  - Prevalence and characterization of cephalosporin resistance in nonpathogenic
      Escherichia coli from food-producing animals slaughtered in Poland.
AB  - The prevalence of Escherichia coli with putative extended-spectrum cephalosporin
      resistance was assessed in cattle, pigs, broilers, layers, and turkey slaughtered
      in Poland. The occurrence of random E. coli isolates recovered from MacConkey
      agar plates with non-wild-type minimal inhibitory concentrations for cefotaxime
      and ceftazidime reached 0.6% in layers, 2.3% in turkey, and 4.7% in broilers,
      whereas all cattle and pigs isolates fell into the wild-type subpopulation. The
      use of MacConkey agar supplemented with cefotaxime (2 mg/L) increased the
      recovery of resistant strains up to 33.3% of samples from pigs, 42.3% from
      layers, 48.0% from turkey, and 54.5% from broilers. Still, no cephalosporin
      resistant E. coli was found in cattle. E-test identified extended-spectrum beta
      lactamase (ESBL) and ampC-type resistance phenotypes in 15 and 33 strains,
      respectively. Molecular characterization identified CTX-M-1 gene in 13 ESBL
      strains, 5 of which possessed also TEM-1b. One strain harbored SHV-12 gene. CMY-2
      was found in all of 20 tested ampC-type cephalosporinase-positive strains either
      alone (n = 14) or in combination with mutations in ampC promoter region (n = 6).
      CTX-M-1 and CMY-2 genes were noted also in five strains from laying hens and
      broilers originated from Belgium and Germany. Nosocomial infections in Poland are
      caused by E. coli carrying other determinants than those found in our study.
      Thus, our results indicate that animals colonized with cephalosporin-resistant
      strains might not be the major source of human infections in Poland. However, the
      contribution to community-acquired infections by spread of resistant clones or
      resistance genes may not be excluded.

PMID- 21721934
TI  - Ethnic disparities in breast tumor phenotypic subtypes in Hispanic and non
      Hispanic white women.
AB  - AIMS: Hispanic women are at a lower risk of getting breast cancer than non
      Hispanic white (NHW) women, yet they experience a higher risk of mortality after
      diagnosis. There is some evidence to suggest differences in tumor pathology;
      however, very limited research has been published on Hispanic women. This
      represents one of the first studies to evaluate the prevalence of tumor markers
      and phenotypic subtypes that are associated with poorer prognosis (human
      epidermal growth factor receptor 2 [HER2], triple negative and basal-like tumors)
      among Hispanic women. METHODS: We reviewed pathology reports, obtained paraffin
      blocks of breast cancer tissue, and established tissue microarrays from NHW
      (n=119) and Hispanic women (n=69) who were Colorado participants in the 4-Corners
      Breast Cancer Study. We evaluated ethnic differences in the prevalence of tumor
      markers and phenotypic subtypes and assessed the contribution of risk factors in
      explaining the observed differences. RESULTS: Consistent with other studies,
      Hispanic women had a higher prevalence of estrogen receptor-negative tumors
      compared with NHWs (36.2% vs. 22.7%, p=0.05). Hispanics also had an unexpectedly
      higher proportion of HER2-positive tumors compared with NHWs (31.9% vs. 14.3%,
      p<0.01). Independent of other prognostic factors, Hispanics were 2.8 times more
      likely to have a HER2-positive tumor (95% confidence interval [CI] 0.98-7.86).
      Hispanics were less likely to have the more favorable luminal A subtype, but no
      significant differences were observed for the less favorable basal-like or triple
      negative subtypes. However, there were suggestive differences when considering
      menopausal status. CONCLUSIONS: These findings provide evidence that breast
      cancers among Hispanic women comprise a distinct spectrum of tumor subtypes when
      compared with NHW women.

PMID- 21721935
TI  - Interaction of calf thymus DNA with the antiviral drug Lamivudine.
AB  - One approach to accelerate the availability of new cancer drugs is to test drugs
      approved for other conditions as anticancer agents. In recent years, some
      researchers have shown that antiviral drugs, such as ritonavir, saquinavir, and
      nelfinavir, inhibit the growth of over 60 cancer cell lines derived from nine
      different tumor types. This article studied the anticancer potential of an
      antiviral drug, lamivudine (LA). The interaction of LA and calf thymus DNA (CT
      DNA) was studied using emission, absorption, circular dichroism (CD), and
      viscosity techniques. The binding constants evaluated from fluorescence data at
      different temperatures revealed that fluorescence enhancement is a static process
      that involves complex-DNA formation in the ground state. Further, the enthalpy
      and entropy of the reaction between the drug and CT-DNA showed DeltaH<0 (
      126.38+/-0.61 kJ mol(-1)) and DeltaS<0 (-352.17+/-2.1 J mol(-1) K(-1));
      therefore, van der Waals interactions or hydrogen bonds are the main forces in
      the binding of LA to CT-DNA. The values of K(f) clearly underscore the high
      affinity of LA to DNA. In addition, detectable changes in the CD spectrum of CT
      DNA in the presence of LA indicated conformational changes. All these results
      showed that groove binding is the binding mode of this drug and CT-DNA.

PMID- 21721936
TI  - The individual experience of unemployment.
AB  - This review describes advances over the past decade in what is known about the
      individual experience of unemployment, predictors of reemployment, and
      interventions to speed employment. Research on the impact of unemployment has
      increased in sophistication, strengthening the causal conclusion that
      unemployment leads to declines in psychological and physical health and an
      increased incidence of suicide. This work has elucidated the risk factors and
      mechanisms associated with experiencing poor psychological health during
      unemployment; less so for physical health and suicide. Psychologists have begun
      to contribute to the study of factors associated with reemployment speed and
      quality. The past decade has especially illuminated the role of social networks
      and job search intensity in facilitating reemployment. Evidence suggests some
      individuals, especially members of minority groups, may face discrimination
      during their job search. Although more work in this arena is needed, several
      intervention-based programs have been shown to help individuals get back to work
      sooner.

PMID- 21721937
TI  - Metabolic pathways required for the intracellular survival of Leishmania.
AB  - Leishmania spp. are sandfly-transmitted parasitic protozoa that cause a spectrum
      of important diseases and lifelong chronic infections in humans. In the mammalian
      host, these parasites proliferate within acidified vacuoles in several phagocytic
      host cells, including macrophages, dendritic cells, and neutrophils. In this
      review, we discuss recent progress that has been made in defining the nutrient
      composition of the Leishmania parasitophorous vacuole, as well as metabolic
      pathways required by these parasites for virulence. Analysis of the virulence
      phenotype of Leishmania mutants has been particularly useful in defining carbon
      sources and nutrient salvage pathways that are essential for parasite persistence
      and/or induction of pathology. We also review data suggesting that intracellular
      parasite stages modulate metabolic processes in their host cells in order to
      generate a more permissive niche.

PMID- 21721938
TI  - Capsules of Streptococcus pneumoniae and other bacteria: paradigms for
      polysaccharide biosynthesis and regulation.
AB  - Capsular polysaccharides and exopolysaccharides play critical roles in bacterial
      survival strategies, and they can have important medical and industrial
      applications. An immense variety of sugars and glycosidic linkages leads to an
      almost unlimited diversity of potential polysaccharide structures. This diversity
      is reflected in the large number of serologically and chemically distinct
      polysaccharides that have been identified among both gram-positive and gram
      negative bacteria. Despite this diversity, however, the genetic loci and
      mechanisms responsible for polysaccharide biosynthesis exhibit conserved features
      and can be classified into a small number of groups. In Streptococcus pneumoniae,
      capsule synthesis occurs by one of two distinct mechanisms that involve the
      polymerization of either individual sugars in a processive reaction (synthase
      dependent) or discrete repeat units in a nonprocessive reaction (Wzy dependent).
      Characterization of these systems has provided novel insights that are applicable
      to polymers synthesized by many gram-positive and gram-negative bacteria, as well
      as eukaryotes.

PMID- 21721939
TI  - Personalized medicine: progress and promise.
AB  - Personalized medicine is a broad and rapidly advancing field of health care that
      is informed by each person's unique clinical, genetic, genomic, and environmental
      information. Personalized medicine depends on multidisciplinary health care teams
      and integrated technologies (e.g., clinical decision support) to utilize our
      molecular understanding of disease in order to optimize preventive health care
      strategies. Human genome information now allows providers to create optimized
      care plans at every stage of a disease, shifting the focus from reactive to
      preventive health care. The further integration of personalized medicine into the
      clinical workflow requires overcoming several barriers in education,
      accessibility, regulation, and reimbursement. This review focuses on providing a
      comprehensive understanding of personalized medicine, from scientific discovery
      at the laboratory bench to integration of these novel ways of understanding human
      biology at the bedside.

PMID- 21721940
TI  - Rapid turnover of functional sequence in human and other genomes.
AB  - The amount of a genome's sequence that is functional has been surprisingly
      difficult to estimate accurately. This has severely hindered analyses asking
      whether the amount of functional genomic sequence correlates with organismal
      complexity. Most studies estimate these amounts by considering nucleotide
      substitution rates within aligned sequences. These approaches show reduced power
      to identify sequence that is aligned, functional, and constrained only within
      narrowly defined phyla. The neutral indel model exploits insertions or deletions
      (indels) rather than substitutions in predicting functional sequence.
      Surprisingly, this method indicates that half of all functional sequence is
      specific to individual eutherian lineages. This review considers the rates at
      which coding or noncoding and functional or nonfunctional sequence changes among
      mammalian genomes. In contrast to the slow rate at which protein-coding sequence
      changes, functional noncoding sequence appears to change or be turned over at
      rapid rates in mammals.

PMID- 21721941
TI  - The genetics of innocence: analysis of 194 U.S. DNA exonerations.
AB  - This new analysis of 194 DNA exonerations, representing 171 criminal events,
      examines the types of evidence and DNA testing that have been used to free the
      victims of wrongful conviction. The types of DNA testing used to free the
      innocent parallels the growth of these techniques in forensic science. Short
      tandem repeat (STR) analysis now prevails (70%), though Y-STR analysis (16%) and
      mitochondrial testing (10%) are still used when STR analysis is not feasible, and
      the recently developed mini-STRs have been used for exonerations since 2008
      (2.6%). The types of exculpatory evidence included intimate swabs (65%), clothing
      (53%), hair (13%), fingernail evidence (5%), cigarettes (3%), and other evidence.
      The most common factor associated with wrongful convictions was misidentification
      (75%), including misidentification by the victim (65%). False confessions
      (including admissions and pleas) were obtained in 30% of the cases, and informant
      testimony (including jailhouse and government informants) was used in 22% of the
      false convictions. Several types of invalid forensic science testimony were used
      to wrongfully convict in the 146 trials where transcripts or reliable forensic
      science data were available for analysis. Invalid testimony included serology
      (38%), hair comparison (22%), fingerprint comparison (2%), and bite mark
      comparison (3%). In 43% of the exonerations, the true perpetrator of the crime
      was identified through postconviction testing.

PMID- 21721942
TI  - Regulatory variation within and between species.
AB  - Understanding how individuals differ from one another and from closely related
      species is a fundamental problem in biology. Recent evidence suggests that much
      of the variation both within and between species is due to differential gene
      regulation. Here we review differential gene regulation focusing on evolutionary
      developmental (evo-devo) biology, global comparison of genomic sequences, whole
      genome gene expression, and transcription factor (TF) binding profiles. We also
      explore the relationship between divergence rate of regulatory sequences, coding
      sequences, and TF binding events using several different measures and discuss
      their implications in the context of evolution of regulatory networks. Finally,
      we discuss the current status and future challenges in relating regulatory
      variation to the divergence across and within species.

PMID- 21721943
TI  - Comparative genetics and genomics of nematodes: genome structure, development,
      and lifestyle.
AB  - Nematodes are found in virtually all habitats on earth. Many of them are
      parasites of plants and animals, including humans. The free-living nematode,
      Caenorhabditis elegans, is one of the genetically best-studied model organisms
      and was the first metazoan whose genome was fully sequenced. In recent years, the
      draft genome sequences of another six nematodes representing four of the five
      major clades of nematodes were published. Compared to mammalian genomes, all
      these genomes are very small. Nevertheless, they contain almost the same number
      of genes as the human genome. Nematodes are therefore a very attractive system
      for comparative genetic and genomic studies, with C. elegans as an excellent
      baseline. Here, we review the efforts that were made to extend genetic analysis
      to nematodes other than C. elegans, and we compare the seven available nematode
      genomes. One of the most striking findings is the unexpectedly high incidence of
      gene acquisition through horizontal gene transfer (HGT).

PMID- 21721944
TI  - Wound repair: toward understanding and integration of single-cell and
      multicellular wound responses.
AB  - The importance of wound healing to medicine and biology has long been evident,
      and consequently, wound healing has been the subject of intense investigation for
      many years. However, several relatively recent developments have added new
      impetus to wound repair research: the increasing application of model systems;
      the growing recognition that single cells have a robust, complex, and medically
      relevant wound healing response; and the emerging recognition that different
      modes of wound repair bear an uncanny resemblance to other basic biological
      processes such as morphogenesis and cytokinesis. In this review, each of these
      developments is described, and their significance for wound healing research is
      considered. In addition, overlapping mechanisms of single-cell and multicellular
      wound healing are highlighted, and it is argued that they are more similar than
      is often recognized. Based on this and other information, a simple model to
      explain the evolutionary relationships of cytokinesis, single-cell wound repair,
      multicellular wound repair, and developmental morphogenesis is proposed. Finally,
      a series of important, but as yet unanswered, questions is posed.

PMID- 21721946
TI  - The role of MeCP2 in the brain.
AB  - Methyl-CpG binding protein 2 (MeCP2) was first identified in 1992 as a protein
      that binds specifically to methylated DNA. Mutations in the MECP2 gene were later
      found to be the cause of an autism spectrum disorder, Rett syndrome. Despite
      almost 20 years of research into the molecular mechanisms of MeCP2 function, many
      questions are yet to be answered conclusively. This review considers several key
      questions and attempts to evaluate the current state of evidence. For example, is
      MeCP2 just a methyl-CpG binding protein? Is it a multifunctional protein or
      primarily a transcriptional repressor? We also consider whether MeCP2, as a
      chromosome-binding protein, acts at specific sites within the genome or more
      globally, and in which cell types it is functionally important. Finally, we
      consider two alternative views of MeCP2 in the brain: as a regulator of brain
      development or as a factor that helps maintain neuronal/glial function.

PMID- 21721945
TI  - Membrane-anchored serine proteases in vertebrate cell and developmental biology.
AB  - Analysis of vertebrate genome sequences at the turn of the millennium revealed
      that a vastly larger repertoire of enzymes execute proteolytic cleavage reactions
      within the pericellular and extracellular environments than was anticipated from
      biochemical and molecular analysis. Most unexpected was the unveiling of an
      entire new family of structurally unique multidomain serine proteases that are
      anchored directly to the plasma membrane. Unlike secreted serine proteases, which
      function primarily in tissue repair, immunity, and nutrient uptake, these
      membrane-anchored serine proteases regulate fundamental cellular and
      developmental processes, including tissue morphogenesis, epithelial barrier
      function, ion and water transport, cellular iron export, and fertilization. Here
      the cellular and developmental biology of this fascinating new group of proteases
      is reviewed. Particularly highlighted is how the study of membrane-anchored
      serine proteases has expanded our knowledge of the range of physiological
      processes that require regulated proteolysis at the cell surface.

PMID- 21721947
TI  - A comparative evaluation of lingual retainer failure bonded with or without
      liquid resin.
AB  - OBJECTIVE: To prospectively evaluate and compare the effect of liquid resin on
      lingual retainer failure after a 2-year follow-up. MATERIALS AND METHODS: Fifty
      two patients (26 males, 26 females) with a mean age of 18.3 +/- 1.3 years at
      follow-up, were randomized into two groups: the resin group and the nonresin
      group. The lingual retainers in the resin group were bonded to the enamel
      surfaces with two-step bonding resin, Optibond FL, and Tetric EvoFlow. The
      nonresin group followed the same procedure of bonding retainers but without
      applying the Optibond FL. Retainer failure, calculus accumulation, and
      discoloration of composite pads adjacent to the retainers during the 2-year
      observation period were registered, compared, and statistically analyzed with a
      Fisher's exact test and chi-square test. RESULTS: In the resin group, the
      incidence of retainer failure was 4% and occurred at the composite-wire
      interface; in the nonresin group, the incidence was 27% and occurred at the
      enamel-composite interface. The difference between the groups was statistically
      significant (P  =  .049). The incidences of calculus accumulation and
      discoloration adjacent to the composite pads were 27% and 69% (P  =  .003 and P <
      .001) higher in the nonresin group, respectively. CONCLUSION: Application of
      resin in bonding of lingual retainers appears to reduce the incidence of retainer
      failure as well as the incidence of calculus accumulation and discoloration
      adjacent to the composite pads.

PMID- 21721948
TI  - Success rate of miniplate anchorage for bone anchored maxillary protraction.
AB  - OBJECTIVE: To evaluate the success rate of Bollard miniplate anchorage for bone
      anchored maxillary protraction (BAMP). MATERIALS AND METHODS: Twenty-five
      consecutive patients (mean age, 12.0 +/- 1.2 years; range, 8.7-14.8 years) with
      maxillary hypoplasia without congenital or acquired deformation were included in
      this study. A total of 100 Bollard modified miniplates were placed by the same
      surgeon. Ninety-nine miniplates were inserted under general anesthesia, and one
      was placed under local anesthesia because of initially soft bone conditions.
      Loading of the miniplates with 150 g elastics was initiated at 17.5 +/- 6.9 days
      (range, 11-38 days) after surgery. Mean follow-up was provided at 20.8 +/- 11.1
      months (range, 6.5-46.2 months). RESULTS: The overall success rate of miniplate
      anchorage in terms of stability was 97%. During orthodontic loading, five
      miniplates showed signs of mobility. After interruption of loading over 2 months,
      two miniplates became stable again. However, a total of three miniplates needed
      to be removed and were successfully replaced under local anesthesia after a mean
      healing period of 3 months. CONCLUSION: Skeletal anchorage by means of Bollard
      modified miniplates is effective for BAMP. Success depends on proper presurgical
      patient counseling, minimal invasive surgery, good postsurgical instructions, and
      orthodontic follow-up.

PMID- 21721949
TI  - Mechanical properties and surface characterization of translucent composite wire
      following topical fluoride treatment.
AB  - OBJECTIVE: To determine the effects of a fluoride prophylactic agent on the
      mechanical properties and surface quality of a preformed round translucent
      composite archwire while comparing it with nickel-titanium (Ni-Ti) and
      multistranded stainless steel wires. MATERIALS AND METHODS: The wires were
      immersed in an acidulated phosphate fluoride solution (APF) or in distilled water
      (control) for 1.5 hours at 37 degrees C. Flexural modulus of elasticity (E) and
      yield strength (YS) of the wires were measured using a three-point bending test
      in a universal testing machine. The springback ratio (YS/E) was calculated for
      each wire. The influence of fluoride treatment on properties of the wires was
      statistically analyzed using Student's t-test at alpha  =  .05. Surface changes
      were observed with a scanning electron microscope. RESULTS: Fluoride treatment
      produced a statistically significant reduction in E, YS, and YS/E of the
      composite wire (P < .05). In addition, a significant decrease in E of Ni-Ti wire
      was found after exposure to fluoride, upon comparison with distilled water
      control treatment. On the other hand, no significant effect of fluoride treatment
      was found on YS and YS/E of Ni-Ti wire and on studied properties of the
      multistranded stainless steel wire (P > .05). Corrosive changes in surface
      topography were observed after exposure to the fluoride agent and were more
      pronounced with the composite wire. CONCLUSIONS: These results suggest that using
      a topical fluoride agent with translucent composite wire could decrease the
      mechanical properties and might damage the surface of the wire, potentially
      contributing to prolonged orthodontic treatment.

PMID- 21721950
TI  - Update in chronic obstructive pulmonary disease: role of antioxidant and
      metabolizing gene polymorphisms.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by systemic and
      local chronic inflammation and oxidative stress. The sources of the increased
      oxidative stress in COPD patients derive from the increased burden of inhaled
      oxidants such as cigarette smoke and other forms of particulate or gaseous air
      pollution and from the increase in reactive oxygen species (ROS) generated by
      several inflammatory, immune, and structural airways cells. There is increasing
      evidence that genetic factors may also contribute to the pathogenesis if COPD,
      particularly antioxidant genes, which may confer a susceptibility to
      environmental insults such as cigarette smoke and thereafter development of COPD.
      Consequently, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase
      (CAT), glutathione S-transferase (GST), microsomal epoxide hydrolase (EPHX1), and
      cytochrome P450 (CYP) genetic polymorphisms may have an important role in COPD
      pathogenesis. In this review the authors summarized the most recent findings
      dealing with these antioxidant genes contributing to the free radical
      neutralization and xenobiotic enzymes playing a role in different phases of cell
      detoxification reactions related to the redox status imbalance in COPD, with an
      emphasis on their possible roles in disease progression.

PMID- 21721951
TI  - Neutral lipid trafficking regulates alveolar type II cell surfactant phospholipid
      and surfactant protein expression.
AB  - Adipocyte differentiation-related protein (ADRP) is a critically important
      protein that mediates lipid uptake, and is highly expressed in lung
      lipofibroblasts (LIFs). Triacylglycerol secreted from the pulmonary circulation
      and stored in lipid storage droplets is a robust hormonal-, growth factor-, and
      stretch-regulated precursor for surfactant phospholipid synthesis by alveolar
      type II epithelial (ATII) cells. A549 lung epithelial cells rapidly take up green
      fluorescent protein (GFP)-ADRP fusion protein-associated lipid droplets (LDs) in
      a dose-dependent manner. The LDs initially localize to the perinuclear region of
      the cell, followed by localization in the cytoplasm. Uptake of ADRP-LDs causes a
      time- and dose-dependent increase in surfactant protein-B (SP-B) expression. This
      mechanism can be inhibited by either actinomycin D or cycloheximide, indicating
      that ADRP-LDs induce newly synthesized SP-B. ADRP-LDs concomitantly stimulate
      saturated phosphatidylcholine (satPC) synthesis by A549 cells, which is inhibited
      by ADRP antibody, indicating that this is a receptor-mediated mechanism.
      Intravenous administration of GFP-ADRP LDs to adult rats results in dose
      dependent increases in lung ADRP and SP-B expression. These data indicate that
      lipofibroblast-derived ADRP coordinates ATII cells' synthesis of the surfactant
      phospholipid-protein complex by stimulating both satPC and SP-B. The authors
      propose, therefore, that ADRP is the physiologic determinant for the elusive
      coordinated, stoichiometric synthesis of surfactant phospholipid and protein by
      pulmonary ATII cells.

PMID- 21721952
TI  - Cathepsin K deficiency aggravates lung injury in hyperoxia-exposed newborn mice.
AB  - Cathepsin K (CatK) is a potent collagenase and elastase and may be involved in
      the development of neonatal bronchopulmonary dysplasia. The authors evaluated the
      effects of CatK deletion on neonatal lung development and response to prolonged
      hyperoxic challenge. CatK deficiency resulted in thinner alveolar walls than wild
      type littermates on postnatal day (PN) 7. However, no morphological difference
      could be detected between CatK-deficient and control groups on PN 14. Exposure to
      90% oxygen for 7 days after birth caused intensive CatK expression in the
      bronchial epithelium and alveolar macrophages of wild-type mice. Hyperoxia caused
      fatal respiratory distress in both groups of mice. However, whereas ~20% of wild
      type mice survived for 2 weeks in hyperoxia, all CatK-deficient mice died within
      the first 9 postnatal days. Hyperoxia-exposed lungs of CatK-deficient mice
      contained high number of macrophages and multinucleated giant cells and had
      increased content of reduced glutathione, indicating intensified pulmonary
      oxidative stress. These results suggest that CatK is involved in pulmonary
      development and it may be an important host-defence protease in the oxygen
      stressed newborn lung.

PMID- 21721953
TI  - The use of health fairs in health promotion.
AB  - Health fairs have been a typical intervention for most worksite and community
      health promotion programs. They are often one of the first types of intervention
      selected for use. Historically, they can be traced back to public health
      interventions conducted at 19th century county and state fairs, and have shown
      considerable sustaining resilience over time. A proposed 21st-century
      modification includes the concept of virtual health fairs, which use the Internet
      and provide a cyber version of the traditional health fair. Various programming
      strategies are proposed that have the potential to enhance the behavior change,
      risk mitigation, and economic return associated with health fairs.

PMID- 21721954
TI  - Food-related environmental, behavioral, and personal factors associated with body
      mass index among urban, low-income African-American, American Indian, and
      Caucasian women.
AB  - PURPOSE: To examine racial/ethnic differences in relationships between food
      related environmental, behavioral and personal factors and low-income women's
      weight status using Social Cognitive Theory (SCT) as a framework. DESIGN: Cross
      sectional survey. SETTING: Community sites and low-income housing developments in
      the Twin Cities metropolitan area. SUBJECTS: Low-income African-American,
      American Indian, and Caucasian women >=18 years old (n  =  367). MEASURES:
      Participants completed a survey including demographic, food security, and
      theoretically based questions. Heights and weights were measured to determine
      body mass index (BMI). ANALYSIS: Data were split by race/ethnicity and reduced by
      examining Pearson coefficients for SCT survey questions significantly correlated
      with BMI (p < .05). Separate environmental, behavioral, and personal multiple
      linear regression models for each racial/ethnic group were run to explore the
      proportion of variance in BMI explained by each SCT construct and which questions
      were significant predictors. RESULTS: All regression models were statistically
      significant, although the personal regression models predicted the greatest
      proportion of the variance in BMI for African-American (15% of the variance),
      American Indian (22% of the variance), and Caucasian women (37% of the variance).
      CONCLUSION: Effective nutrition education and intervention efforts to control the
      obesity epidemic among urban, low-income women may call for a tailored approach
      with noted consideration of their racial/ethnic identity. Although broader
      changes to the food environment are necessary, the importance of addressing
      personal factors such as nutrition knowledge, self-efficacy, and emotional coping
      responses to stress, in the context of income constraints, food insecurity, and
      health beliefs, is also implicated.

PMID- 21721955
TI  - Developing and testing the CHORDS: Characteristics of Responsible Drinking
      Survey.
AB  - PURPOSE: Report on the development and psychometric testing of a theoretically
      and evidence-grounded instrument, the Characteristics of Responsible Drinking
      Survey (CHORDS). DESIGN: Instrument subjected to four phases of pretesting
      (cognitive validity, cognitive and motivational qualities, pilot test, and item
      evaluation) and a final posttest implementation. SETTING: Large public university
      in Texas. SUBJECTS: Randomly selected convenience sample (n  =  729) of currently
      enrolled students. MEASURES: This 78-item questionnaire measures individuals'
      responsible drinking beliefs, motivations, intentions, and behaviors. Cronbach
      alpha, split-half reliability, principal components analysis and Spearman rho
      were conducted to investigate reliability, stability, and validity. RESULTS:
      Measures in the CHORDS exhibited high internal consistency reliability and strong
      correlations of split-half reliability. Factor analyses indicated five distinct
      scales were present, as proposed in the theoretical model. Subscale composite
      scores also exhibited a correlation to alcohol consumption behaviors, indicating
      concurrent validity. CONCLUSIONS: The CHORDS represents the first instrument
      specifically designed to assess responsible drinking beliefs and behaviors. It
      was found to elicit valid and reliable data among a college student sample. This
      instrument holds much promise for practitioners who desire to empirically
      investigate dimensions of responsible drinking.

PMID- 21721957
TI  - Workplace health promotion will become irrelevant in national policy if we do not
      learn to speak with one voice.

PMID- 21721959
TI  - Facing the facelessness of public health: what's the public got to do with it?
AB  - Despite compelling statistics that show we could eliminate 80%of all heart
      disease and strokes, 90% of all diabetes, and 60% of all cancers with basic
      lifestyle changes, we have failed to motivate the public to make these changes
      and failed to motivate policy makers to make healthy choices the easiest choice.
      Dr. Katz suggests we have failed because we have focused too much on statistics
      and too little on passion. He implores all of us to tap into people's passion by
      connecting each of these statistics with a human story.

PMID- 21721960
TI  - The effectiveness of a walking booster program for seniors.
AB  - PURPOSE: To determine the effectiveness of a 3-month home-based booster program
      for seniors to increase walking. DESIGN: A longitudinal prospective study.
      SETTING: Perth, Western Australia. SUBJECTS: Of the 177 (of 260) program
      participants and 236 (of 313) controls who initially completed the neighborhood
      walking intervention, 114 (64%) and 134 (57%) were available for the booster, and
      100 and 131 participants completed the entire program, respectively.
      INTERVENTION: A 6-month neighborhood walking intervention was followed 12 months
      later by a 3-month home-based booster program comprised of print-based materials,
      a pedometer, and two motivational phone calls. MEASURES: A self-reported
      questionnaire was administered at four time points: original intervention,
      baseline (t1) and 6 months (t2); booster, 18 months (t3) and 21 months (t4).
      Physical activity levels were measured using the International Physical Activity
      Questionnaire. Personal and demographic information was collected. ANALYSIS:
      Descriptive statistics and repeated-measures analysis of variance. RESULTS: The
      intervention group's mean time spent walking for recreation and mean time spent
      walking for errands per week showed significant increases between t1 and t2, but
      the weekly mean time walking for recreation dropped by 52 minutes from t2 to t3.
      Significant increases were evident from t3 to t4 as a result of the booster.
      Walking levels for the control group remained stable over the study period.
      CONCLUSION: Physical activity levels of seniors revert once an intervention
      concludes. A home-based booster program can reactivate physical activity levels.
      Hence, program planners should include booster sessions for program
      sustainability.

PMID- 21721961
TI  - School travel plans: preliminary evidence for changing school-related travel
      patterns in elementary school children.
AB  - PURPOSE: In New Zealand, the School Travel Plan (STP) program was developed to
      increase school-related active travel rates and decrease traffic congestion. The
      plan was developed through collaboration among the school, community, and local
      council. The STP was tailored to each school's specific needs and incorporated
      educational initiatives, physical infrastructural changes in the vicinity of
      schools, and policy development. The purpose of this study was to determine the
      effectiveness of the STP program in changing school travel modes in children.
      DESIGN: Effectiveness was assessed by determining the difference between pre-STP
      and follow-up travel mode data in schools. The differences were assessed using
      multilinear regression analysis, including decile (measure of socioeconomic
      status), school roll at baseline, and STP year of implementation as predictors.
      SETTING: Thirty-three elementary schools from the Auckland region participated in
      the study. School size ranged from 130 to 688 students. SUBJECTS: The final 2006
      sample consisted of 13,631 students. MEASURES: On a set day (pre- and post-STP),
      students indicated their mode of transport to school and intended mode for
      returning home that day. RESULTS: Differences are reported as percentage points:
      there was an increase in active transport by 5.9% +/- 6.8% when compared to
      baseline travel modes. School roll, STP year of implementation, and baseline
      values predicted engagement with active transport. CONCLUSION: Preliminary
      findings suggest that the STP program may be successful in creating mode shift
      changes to favor school-related active travel in elementary-school children.

PMID- 21721962
TI  - Medication adherence among rural, low-income hypertensive adults: a randomized
      trial of a multimedia community-based intervention.
AB  - PURPOSE: Examine the effectiveness of a community-based, multimedia intervention
      on medication adherence among hypertensive adults. DESIGN: Randomized controlled
      trial. SETTING: Rural south Alabama. SUBJECTS: Low-income adults (N  =  434)
      receiving medication at no charge from a public health department or a Federally
      Qualified Health Center. INTERVENTION: Both interventions were home-based and
      delivered via computer by a community health advisor. The adherence promotion
      (AP) intervention focused on theoretical variables related to adherence (e.g.,
      barriers, decisional balance, and role models). The cancer control condition
      received general cancer information. MEASURES: Adherence was assessed by pill
      count. Other adherence-related variables, including barriers, self-efficacy,
      depression, and sociodemographic variables, were collected via a telephone
      survey. ANALYSIS: Chi-square analysis tested the hypothesis that a greater
      proportion of participants in the AP intervention are >=80% adherent compared to
      the control group. General linear modeling examined adherence as a continuous
      variable. RESULTS: Participants receiving the intervention did not differ from
      individuals in the control group (51% vs. 49% adherent, respectively; p  =  .67).
      Clinic type predicted adherence (p < .0001), as did forgetting to take
      medications (p  =  .01) and difficulty getting to the clinic to obtain
      medications (p < .001). CONCLUSIONS: Multilevel interventions that focus on
      individual behavior and community-level targets (e.g., how health care is
      accessed and delivered) may be needed to improve medication adherence among low
      income rural residents.

PMID- 21721963
TI  - Awareness and reported consequences of a cigarette tax increase among older
      adolescents and young adults.
AB  - PURPOSE: To determine the prevalence and predictors of the awareness of cigarette
      price increases following a cigarette tax increase, and assess the association of
      the tax increase and attempts to quit and reduce smoking among adolescents and
      young adults. DESIGN: We used a prospective cohort design. SETTING: Surveys were
      conducted in Minnesota before and after a $0.75 cigarette tax increase. SUBJECTS:
      We surveyed 3167 adolescents and young adults, including a subsample of 781 past
      30-day smokers. MEASURES: Outcome measures were awareness of cigarette price
      increases and, among past-30-day smokers, reported changes in smoking behaviors
      because of the tax increase. Predictors included demographics, social factors,
      and prior smoking behaviors. ANALYSIS: We estimated the prevalence of the
      outcomes and their associations with the predictors using logistic regression.
      RESULTS: Among all participants, 42% noticed an increase in cigarette prices
      after the tax increase, including 76% of past-30-day smokers. Being a heavier
      smoker, living with smokers, having more smoking close friends, and generally
      being aware of cigarette price changes prospectively predicted the awareness of
      the price increase after the tax increase. Among past-30-day smokers, 16.7%
      reported quit attempts and 24.1% reported reducing smoking because of the tax
      increase. CONCLUSION: Because fewer than half of the participants noticed the
      cigarette tax increase, media campaigns to raise awareness of tax changes may
      increase their effectiveness.

PMID- 21721964
TI  - Knowledge and perceptions of smoking according to income level in Morocco.
AB  - PURPOSE: To determine the association between income level and variations in
      knowledge and perceptions about tobacco smoking in Morocco. DESIGN: Cross
      sectional study. SETTING: Random sample of 9195 subjects representative of the
      Moroccan population. SUBJECTS: Subjects aged >15 years from households. MEASURES:
      Data were collected from selected households using a standardized questionnaire
      about smoking, educational level, household monthly income, and knowledge of
      health effects of smoking. ANALYSIS: Stepwise logistic regression was used for
      multivariate analysis. Adjusted odds ratios with 95% confidence intervals for
      each variable were calculated as an estimate of the likelihood of having
      knowledge that smoking causes selected diseases. RESULTS: Among 9195 subjects,
      27.8% reported low income (<2000 Moroccan dirhams [MAD]), and 9.9% reported the
      highest income level (>=6000 MAD). Higher income was significantly associated
      with higher knowledge of health effects of smoking (p < .0001); 55% of low-income
      respondents compared to 71.5% of respondents with higher income knew about the
      relationship between cigarette smoking and cancer. CONCLUSIONS: Lower income
      level was associated with lower awareness of the harms of smoking. There is a
      need to improve knowledge of the dangers of smoking among the disadvantaged
      segments of the population.

PMID- 21721965
TI  - Increasing consumer demand among Medicaid enrollees for tobacco dependence
      treatment: the Wisconsin "Medicaid covers it" campaign.
AB  - PURPOSE: Smoking prevalence among Medicaid enrollees is higher than among the
      general population, but use of evidence-based cessation treatment is low. We
      evaluated whether a communications campaign improved cessation treatment
      utilization. DESIGN: Quasi-experimental. SETTING: Wisconsin. SUBJECTS: Enrollees
      in the Wisconsin Family Medicaid program. The average monthly enrollment during
      the study period was approximately 170,000 individuals. INTERVENTION: Print
      materials for clinicians and consumers distributed to 13 health maintenance
      organizations (HMOs) serving Wisconsin Medicaid HMO enrollees. MEASURES:
      Wisconsin Medicaid pharmacy claims data for smoking cessation medications were
      analyzed before and after a targeted communications campaign. HMO enrollees were
      the intervention group. Fee-for-service enrollees were a quasi-experimental
      comparison group. Quit Line utilization data were also analyzed. ANALYSIS:
      Pharmacotherapy claims and number of registered Quit Line callers were compared
      precampaign and postcampaign. RESULTS: Precampaign, cessation pharmacotherapy
      claims declined for the intervention group and increased slightly for the
      comparison group (t  =  2.29, p  =  .03). Postcampaign, claims increased in both
      groups. However, the rate of increase in the intervention group was significantly
      greater than in the comparison group (t  =  -2.2, p  =  .04). A statistically
      significant increase was also seen in the average monthly number of Medicaid
      enrollees that registered for Quit Line services postcampaign compared to
      precampaign (F [1,22]  =  7.19, p  =  .01). CONCLUSION: This natural experiment
      demonstrated statistically significant improvements in both pharmacotherapy
      claims and Quit Line registrations among Medicaid enrollees. These findings may
      help inform other states' efforts to improve cessation treatment utilization.

PMID- 21721966
TI  - An individually based lifestyle intervention for workers at risk for
      cardiovascular disease: a process evaluation.
AB  - PURPOSE: Evaluate counselors' adherence to an intervention protocol, counselors'
      competence, and the associations between three process indicators and body weight
      at follow-up in a 6-month individually based lifestyle intervention for
      construction workers. DESIGN: Process evaluation with qualitative and
      quantitative data. SETTING: Occupational health service. SUBJECTS: A total of 408
      male construction workers with an elevated risk of cardiovascular disease
      received the intervention, and 27 occupational health professionals delivered the
      intervention. INTERVENTION: Seven counseling sessions, the first during which
      four prescribed items had to be discussed. Motivational interviewing (MI) was
      used as a counseling technique. MEASURES AND ANALYSIS: The number of sessions and
      the items discussed were registered by the counselors. Adherence to MI was
      determined by expert scoring of transcripts of random segments of 19 counseling
      sessions. Counselors' competence was rated by participants and counselors
      separately. Associations between three process indicators and body weight at
      follow-up were determined by linear and logistic regression analyses. RESULTS:
      Two-thirds of all participants attended five or more sessions, and 38.5% attended
      all seven sessions. In 90.2% of all cases, the counselor discussed all obligatory
      items in the first session. MI adherence was reached in one audiotaped fragment.
      Most (86.3%) of all participants agreed with the counselor being competent.
      Neither counselors' competence nor number of sessions or items discussed was
      significantly associated with body weight loss. CONCLUSIONS: Performing five
      sessions and discussing four prescribed items was feasible for the counselors,
      whereas performing MI was not. Still, participants were positive about the
      counselors' competence and willing to attend the intervention sessions.
      Investigators are encouraged to report the evaluation of their intervention
      process to improve future lifestyle interventions in research or in practice.

PMID- 21721967
TI  - Physician advice on exercise and diet in a U.S. sample of obese Mexican-American
      adults.
AB  - PURPOSE: To document the prevalence of obese Mexican-Americans never advised by
      health professionals regarding exercise and diet, and to determine risk factors
      for no advice. METHODS: Data came from 1787 obese Mexican-American adults (body
      mass index >=30; age >=18 years) in the Medical Expenditure Panel Survey. The
      survey included self-reported receipt of health care provider advice on exercise
      and diet as well as sociodemographic, health-related, and provider-related
      factors. Multivariable logistic regression models were performed separately for
      advice regarding exercise and advice regarding diet. RESULTS: Overall, 45% of
      respondents reported that they had never received advice from a doctor or health
      care professional to exercise more, and 52% reported that they have received
      advice to eat fewer higher-fat/high-cholesterol foods. Men, nonmarried
      respondents, lower-educated respondents, those who preferred to speak Spanish at
      home, and those without comorbid chronic conditions were less likely to receive
      advice. DISCUSSION: Results suggest that obese Mexican-Americans are
      insufficiently advised by health care providers regarding exercise and diet.
      Given the seriousness of obesity-related health risks and the increasing
      prevalence of overweight status and obesity among Mexican-Americans, it is vital
      that providers are involved in finding ways to effectively educate and/or treat
      overweight patients.

PMID- 21721968
TI  - Physical activity in the context of clustering patterns of health-promoting
      behaviors.
AB  - PURPOSE: To describe differences in physical activity in the context of
      clustering patterns of health-promoting behaviors. DESIGN: A cross-sectional
      study with 1724 participants (response rate, 91.1%). SETTING: Tadami Town, in a
      rural area of Fukushima Prefecture, Japan. SUBJECTS: Part of the general
      population who participated in annual health checkups (age range, 30-93 years).
      MEASURES: The Health-Promoting Lifestyle Profile II was used to assess frequency
      of health-promoting behaviors (physical activity, health responsibility,
      spiritual growth, interpersonal relationships, nutrition, and stress management).
      Smoking status, alcohol consumption, and disease status were self-reported.
      Public health nurses measured the weight and height of participants. ANALYSIS:
      Cluster analysis was conducted to identify clustering patterns of health
      promoting behaviors other than physical activity. Differences in physical
      activity between identified clusters were examined by multiple logistic
      regression analysis. RESULTS: Four clusters were identified and labeled as "Most
      challenged" (20.4%), "Adherence to norms" (30.3%), "Well in mentality" (20.9%),
      and "Health-promoting" (28.4%). "Health-promoting" was the most physically active
      cluster, followed by "Adherence to norms" and "Well in mentality." CONCLUSIONS:
      Although the survey methodology was subject to selection, self-report, and recall
      biases, we have described physical activity in the context of clustering patterns
      of health-promoting behaviors. Laying the groundwork for physical activity in the
      lifestyle is important for establishing health-promotion strategies to increase
      physical activity.

PMID- 21721969
TI  - Psychometric characteristics of process evaluation measures for a rural school
      based childhood obesity prevention study: Louisiana Health.
AB  - PURPOSE: To evaluate the implementation of intervention components of the
      Louisiana Health study, which was a multicomponent childhood obesity prevention
      program conducted in rural schools. DESIGN: Content analysis. SETTING: Process
      evaluation assessed implementation in classrooms, gym classes, and cafeterias.
      SUBJECTS: Classroom teachers (n  =  232), physical education teachers (n  =  53),
      food service managers (n  =  33), and trained observers (n  =  9). MEASURES: Five
      process evaluation measures were created: Physical Education Questionnaire (PEQ),
      Intervention Questionnaire (IQ), Food Service Manager Questionnaire (FSMQ),
      Classroom Observation (CO), and School Nutrition Environment Observation (SNEO).
      ANALYSIS: Interrater reliability and internal consistency were assessed on all
      measures. Analysis of variance and chi(2) were used to compare differences across
      study groups on questionnaires and observations. RESULTS: The PEQ and one
      subscale from the FSMQ were eliminated because their reliability coefficients
      fell below acceptable standards. The subscale internal consistencies for the IQ,
      FSMQ, CO, and SNEO (all Cronbach alpha > .60) were acceptable. CONCLUSIONS: After
      the initial 4 months of intervention, there was evidence that the Louisiana
      Health intervention was being implemented as it was designed. In summary, four
      process evaluation measures were found to be sufficiently reliable and valid for
      assessing the delivery of various aspects of a school-based obesity prevention
      program. These process measures could be modified to evaluate the delivery of
      other similar school-based interventions.

PMID- 21721973
TI  - PPARs and their effects on the cardiovascular system.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors belonging to the nuclear receptor superfamily that undergo
      transactivation or transrepression by distinct mechanisms leading to induction or
      repression of expression of target genes. The PPAR family consists of three
      isoforms, alpha, gamma, and beta/delta, which share similar structural
      organization, possess distinct functions, and vary in their ligand affinity,
      expression, and activity in different metabolic pathways in different tissues.
      PPARs are involved in many functions especially those involved in the regulation
      of vascular tone, inflammation and energy homeostasis and therefore represent
      important targets for hypertension, obesity, obesity-induced inflammation, and
      metabolic syndrome in general. PPARs may influence the inflammatory response
      either by direct transcriptional downregulation of proinflammatory genes via
      mechanisms involving transrepression, or indirectly via their transcriptional
      effects on lipid metabolism. On account of their pleiotropic effects, they are
      now known to be active participants in many disease conditions and they represent
      potent targets for the development of therapy of a wide array of diseases.

PMID- 21721974
TI  - Association of a BLVRA common polymorphism with essential hypertension and blood
      pressure in Kazaks.
AB  - Biliverdin reductase A (BLVRA) is a powerful intracellular antioxidant enzyme and
      an antagonist to insulin-mediated glucose uptake by the cells. Increased
      oxidative stress and insulin-resistance (IR) are associated with increased risk
      for hypertension. Therefore, we hypothesized that BLVRA might be attributable to
      the variation of susceptibility to essential hypertension, and investigated
      single nucleotide polymorphism (SNP) rs699512 (Thr3Ala), the only common non
      synonymous SNP within BLVRA, in population-based samples of 999 Kazak herdsmen
      from the villages in Xinjiang, China. The minor allele of SNP rs699512 reduced
      the risk of essential hypertension (age- and gender-adjusted odds ratio 0.76; 95%
      confidence interval 0.61-0.94; p = 0.010). Single nucleotide polymorphism
      rs699512 showed association with both systolic and diastolic blood pressures: the
      minor allele homozygous carriers had lowest systolic and diastolic blood
      pressures (139.6 mmHg, 89.6mmHg), followed by heterozygous carriers (145.3 mmHg,
      92.3 mmHg), and then major allele homozygous carriers (150.3 mmHg, 95.1 mmHg) (p
      = 0.005 and 0.009, respectively). These findings provide the first genetic
      evidence for the role of BLVRA on the susceptibility to human essential
      hypertension and blood pressure.

PMID- 21721976
TI  - Enhancing the job performance of employees with disabilities using the self
      determined career development model.
AB  - The impact of the Self-Determined Career Development Model (hereafter called the
      Self-Determined Career Model) on the job performance of four adults with moderate
      intellectual disability employed in competitive work settings was examined.
      Employees learned to set work-related goals, develop an action plan, implement
      the plan, and adjust their goals and plans as needed. A multiple baseline design
      across employees was implemented. All participants achieved their self-selected
      goal at levels that exceeded the expectations of their supervisor and job coach.
      Findings extend the current line of research utilizing the Self-Determined Career
      Model and support the use of this model by personnel providing support to
      individuals with disabilities in work settings.

PMID- 21721977
TI  - Factors associated with the early work experiences of adolescents with severe
      disabilities.
AB  - The early work experiences of a nationally representative sample of youth with
      severe disabilities (i.e., intellectual disabilities, autism, multiple
      disabilities) were examined. Using data from the National Longitudinal Transition
      Study-2, we explored the extent to which various student-, family-, school-, and
      community-level factors were associated with paid work experiences during high
      school. Findings highlight the elusiveness of early work experiences for many
      youth with severe disabilities and call attention to malleable factors that may
      play a role in shaping employment success during high school. Recommendations for
      research and practice are highlighted.

PMID- 21721978
TI  - National call for organizational change from sheltered to integrated employment.
AB  - Our purpose in this article is to contend that organizational change from
      sheltered to integrated employment is not only possible but necessary, and a
      federal Employment First agenda must be advanced. Findings are reported from
      interviews with senior managers from 10 organizations that have shifted their
      service delivery to community employment, and recommendations are provided based
      on these findings. Results reveal the commonalities among a diverse group of
      agencies, suggesting the viability of transformation of our current systems with
      the support and leadership of state and federal agencies and programs.

PMID- 21721979
TI  - Connecting employers with people who have intellectual disability.
AB  - Longstanding advocacy for employment opportunity, recent legislative and policy
      developments, and advancements in employment service practice have contributed to
      an emerging notion of presumptive employability for individuals with
      disabilities. Unfortunately, low levels of employment remain the norm for people
      with disabilities, especially those with intellectual disability. Further, an
      examination of employer views of people with intellectual disability suggests
      that effective connections remain elusive between employers and employment
      service programs that support job seekers with intellectual disability. In this
      article employer perspectives are considered and case descriptions of effective
      connections of people with intellectual disability to employers are provided in
      order to meet demand-side operational needs. These perspectives have implications
      for elevating the effectiveness of employment service practice.

PMID- 21721980
TI  - Jobs by 21 partnership project: impact of cross-system collaboration on
      employment outcomes of young adults with developmental disabilities.
AB  - In 2007, the low level of young adults with developmental disabilities who were
      employed in the 3 months postgraduation from high school led the Washington State
      legislature to authorize and fund the Jobs by 21 Partnership Project. The intent
      of the project was to identify and demonstrate best practices in sustainable
      partnerships among Washington State's school and adult service systems. Results
      indicated that participants in the project were more likely to be employed
      following school exit and had stronger employment outcomes than students who did
      not participate. Further, data suggest that improved employment outcomes were
      supported by the leveraging and maximization of financial and in-kind resources
      and the strengthening of collaborative relationships across project stakeholders.

PMID- 21721981
TI  - Choosing employment: factors that impact employment decisions for individuals
      with intellectual disability.
AB  - Little is known about the factors that shape the employment-related decisions of
      individuals with intellectual and/or developmental disabilities. Findings from
      qualitative interviews with individuals, their family members, and employment
      support professionals from four community rehabilitation providers throughout
      Massachusetts were reported. Recognizing the value of participatory action
      research, we also included a co-researcher with intellectual disability who
      participated in all facets of the research process. Findings revealed a
      collection of people and factors considered influential in employment-related
      decision-making. The family in the formative years, school-based staff and early
      employment experiences, the culture of the community rehabilitation providers,
      the job developer, and personal preferences all influenced participants'
      decisions. Through understanding these persuasive elements, we offer
      recommendations to those in the intellectual and developmental disabilities field
      to optimize employment choices and outcomes.

PMID- 21721982
TI  - Employment first: a beginning not an end.

PMID- 21721983
TI  - Employment: it is everybody's business.

PMID- 21721986
TI  - Association between alcohol intake and metabolic syndrome in patients with
      hypertension.
AB  - The aim of this study was to determine how alcohol consumption influences
      metabolic syndrome in patients with hypertension. The subjects were 3938 male
      workers being treated with anti-hypertensive drugs and they were divided into
      four groups by average ethanol intake [non-, light (<22 g/day), moderate (>=22
      and <44 g/day), and heavy (>=44 g/day) drinkers]. The relationships of alcohol
      intake with atherosclerotic risk factors and metabolic syndrome were
      investigated. Waist circumference and hemoglobin A1c were significantly smaller
      and lower, respectively, in light, moderate, and heavy drinkers than in
      nondrinkers. Systolic blood pressure and log-converted triglyceride were
      significantly higher in heavy drinkers than in nondrinkers. HDL cholesterol was
      significantly higher in all of the drinker groups than in nondrinkers and tended
      to be higher as alcohol intake increased. Prevalence of metabolic syndrome was
      significantly lower in light, moderate, and heavy drinkers than in nondrinkers.
      Age- and smoking history-adjusted odds ratios (ORs) vs. nondrinkers for metabolic
      syndrome were significantly low in light drinkers (OR = 0.71, 95% confidence
      interval [CI]: 0.56-0.89), moderate drinkers (OR = 0.64, 95% CI: 0.54-0.75) and
      heavy drinkers (OR = 0.68, 95% CI: 0.57-0.82). The results suggest that alcohol
      drinking is associated with a lower risk of metabolic syndrome in patients with
      hypertension.

PMID- 21721987
TI  - Association of stroke with ambulatory arterial stiffness index (AASI) in
      hypertensive patients.
AB  - The ambulatory arterial stiffness index (AASI) predicted stroke in hypertensive
      patients and in the general populations. However, no similar data was available
      in Chinese. In the present study, we sought confirmation that Chinese
      hypertensive patients with a history of stroke would have an elevated AASI. We
      retrospectively analyzed the data of 156 hypertensive outpatients (60.9 % men;
      mean age, 61.5 years) and 582 inpatients (63.6 % men; 58.6 years) of the
      Hypertension Department at Ruijin Hospital in Shanghai, China. The AASI was
      calculated as 1 - the regression slope of diastolic blood pressure (DBP) on
      systolic blood pressure (SBP) in individual 24-h ambulatory recordings. With
      adjustment applied for sex, age, body mass index (BMI), the 24-h mean arterial
      pressure, and other cardiovascular risk factors, AASI was higher in patients with
      a history of stroke than in patients without stroke in both outpatient (0.51 +/-
      0.02 vs. 0.47 +/- 0.01; P = 0.050) and inpatient (0.46 +/- 0.01 vs. 0.44 +/-
      0.01; P = 0.031) cohorts. The odds ratio (OR) for a history of stroke associated
      with a 1-SD increase in AASI was 1.63 (95% confidence interval (CI), 1.01-2.62; P
      = 0.046) in outpatients, 1.32 (1.01-1.74; P = 0.046) in inpatients, and 1.30
      (1.05-1.62; P = 0.018) in two patient cohorts combined (n = 738) after
      multivariate adjustment including the night-to-day ratio of SBP. Our findings
      suggest that Chinese hypertensive patients with a history of stroke, compared to
      those without such history, have stiffer arteries, as exemplified by a higher
      AASI.

PMID- 21721988
TI  - Treatment of gingival recession defects using coronally advanced flap with a
      porcine collagen matrix compared to coronally advanced flap with connective
      tissue graft: a randomized controlled clinical trial.
AB  - BACKGROUND: Connective tissue graft (CTG) plus coronally advanced flap (CAF) is
      the reference therapy for root coverage. The aim of the present study is to
      evaluate the use of a porcine collagen matrix (PCM) plus CAF as an alternative to
      CTG+CAF for the treatment of gingival recessions (REC), in a prospective
      randomized, controlled clinical trial. METHODS: Eighteen adult patients
      participated in this study. The patients presented 22 single Miller's Class I or
      II REC, randomly assigned to the test (PCM+CAF) or control (CTG+CAF) group. REC,
      probing depth, clinical attachment level (CAL), and width of keratinized tissue
      (KG) were evaluated at 12 months. In addition, the gingival thickness (GT) was
      measured 1mm apical to the bottom of the sulcus. RESULTS: At 12 months, mean REC
      was 0.23 mm for test sites and 0.09 mm for control sites (P <0.01), whereas
      percentage of root coverage was 94.32% and 96.97%, respectively. CAL gain was
      2.41 mm in test sites and 2.95 mm in control sites (P <0.01). KG gain was 1.23 mm
      in the test group and 1.27 mm in the control group (P <0.01). In test sites, GT
      changed from 0.82 to 1.82 mm, and in control sites, from 0.86 to 2.09 mm (P
      <0.01). CONCLUSIONS: Within the limits of the study, both treatment procedures
      resulted in significant reduction in REC at 12 months. No statistically
      significant differences were found between PCM+CAF and CTG+CAF with regard to any
      clinical parameter. The collagen matrix represents a possible alternative to CTG.

PMID- 21721989
TI  - Influence of obesity and bariatric surgery on the periodontal condition.
AB  - BACKGROUND: Recent studies have shown that being overweight or obese is
      associated with a higher risk of periodontitis. However, the literature offers an
      insufficient number of published reports regarding the effect of bariatric
      surgery on oral health. As such, the present study aims to determine the
      association between periodontal status and being overweight/obese in prebariatric
      and postbariatric surgery populations of Brazil. METHODS: Three hundred forty
      five participants between 18 and 60 years of age, from both sexes, were grouped
      according to prebariatric or postbariatric surgery and underwent a complete
      periodontal examination. Biologic, demographic, and behavioral variables were
      analyzed in a Poisson regression model. RESULTS: Considering the timing of
      bariatric surgery, the sample was divided into three groups: PRE-OP
      (preoperative, n = 133), POS-OP1 (postoperative <=6 months, n = 72), and POS-OP2
      (post-surgery >6 months, n = 140). Regardless of the type of surgery (PRE-OP, POS
      OP1, POS-OP2), the prevalence of periodontitis proved to be high (81.45%). There
      was a statistically significant difference in the prevalence of periodontitis
      among the PRE-OP, POS-OP1, and POS-OP2 groups (P = 0.040). In the Poisson
      regression model, after adjusting for biologic, demographic, and behavioral risk
      variables, only bleeding on probing remained significantly associated with the
      prevalence of periodontitis (P <0.001). CONCLUSION: Differences in periodontal
      condition were observed in individuals at different times of the bariatric
      surgery, showing a high prevalence of periodontitis in both preoperative and
      postoperative follow-up.

PMID- 21721990
TI  - Lamb ex vivo model for training in maxillary sinus floor elevation surgery: a
      comparative study with human standards.
AB  - BACKGROUND: Many models have been suggested for surgical training in sinus floor
      elevation (SFE), but information on key features that provide feedback to the
      trainee is scarce. The aim of this study is to compare the thickness of the
      lateral wall of the maxillary sinus (TLWMS) and the thickness of the Schneiderian
      membrane (TSM) between an animal model and the human standard. METHODS: The
      observational study used 20 fresh lamb heads. Cone-beam computed tomography (CT)
      was performed for recording the following: TLWMS, sinus lateral floor width,
      distance from the lateral border of the anteroposterior bone crest to the sinus
      wall, and height of lateral maxillary sinus. Thirty human radiologic exploration
      cone-beam CTs were used for comparisons. The sinus membrane thickness was
      measured at three points per section and compared to those of 10 formalin
      preserved human membranes. RESULTS: TLWMS in the animal model scored 2.25 +/- 0.3
      mm and was thicker than that of humans with subsinusal edentulism (Xi - Xj = 0.3;
      95% confidence interval = 0.1 to 0.4), although this difference was not
      considered clinically relevant. The average thickness of the sinus membrane was
      485.5 +/- 137.1 MUm with no significant differences between sides (P = 0.12) or
      between the thickness of human and lamb Schneiderian membranes. CONCLUSIONS: The
      model based on lambs is potentially useful for training in SFE techniques because
      of the similarities in the TLWMS and particularly the TSM. Additional studies are
      needed to validate this model within a teaching environment.

PMID- 21721991
TI  - Three-dimensional self-organizing neural architectures: a neural stem cells
      reservoir and a system for neurodevelopmental studies.
AB  - Complex microenvironmental stimuli influence neural cell properties. To study
      this, we developed a three-dimensional (3-D) neural culture system, composed of
      different populations including neurons, astrocytes, and neural stem cells
      (NSCs). In particular, these last-mentioned cells represent a source potentially
      exploitable to test drugs, to study neurodevelopment and cell-therapies for
      neuroregenerations. On seeding on matrigel in a medium supplemented with serum
      and mitogens, cells obtained from human fetal brain tissue formed 3-D self
      organizing neural architectures. Immunocytochemical analysis demonstrated the
      presence of undifferentiated nestin+ and CD133+ cells, surrounded by beta-tub
      III+ and GFAP+ cells, suggesting the formation of niches containing potential
      human NSCs (hNSCs). The presence of hNSCs was confirmed by both neurosphere assay
      and RT-PCR, and their multipotentiality was demonstrated by both
      immunofluorescent staining and RT-PCR. Flow cytometry analysis revealed that
      neurosphere forming cells originating from at least two different subsets
      expressing, respectively, CD133 and CD146 markers were endowed with different
      proliferative and differentiation potential. Our data implicate that the
      complexity of environment within niches and aggregates of heterogeneous neural
      cell subsets may represent an innovative platform for neurobiological and
      neurodevelopmental investigations and a reservoir for a rapid expansion of hNSCs.

PMID- 21721992
TI  - Comprehensive periodontal therapy: a statement by the American Academy of
      Periodontology *.

PMID- 21721993
TI  - Is it correct to always consider weight-bearing asymmetrically distributed in
      individuals with hemiparesis?
AB  - Injuries may cause unilateral deterioration of brain areas related to postural
      control resulting in lateralized motor disability with abnormal asymmetry in
      weight-bearing distribution. Although overloading toward the nonaffected limb has
      been described as the preferred posture among individuals with hemiparesis,
      characterization of the weight-bearing asymmetry is poorly and indirectly
      described. Therefore, this study aimed to describe weight-bearing distribution
      during upright stance, establishing criteria to consider asymmetry in hemiparesis
      when analyzed within the limits defined by controls matched by age and gender.
      Forty subjects with (n = 20) or without hemiparesis (n = 20) were included in
      procedures to record weight-bearing values between hemibodies, and these values
      were used to calculate a symmetry ratio. Control presented 95% confidence
      interval (CI) of the mean for symmetry ratio ranging from 0.888 to 1.072,
      defining limits to symmetry. Four subjects with hemiparesis (20%) had symmetry
      ratios inside limits defined by controls (i.e., weight-bearing symmetrically
      distributed), and 11 (55%) subjects without hemiparesis showed symmetry ratios
      outside the limits, suggesting asymmetrical weight-bearing distribution. It was
      concluded that asymmetry, when present in a control group, was more frequently
      overloading nonpredominantly used hemibody (nondominant side), differing from a
      hemiparesis group commonly forced to assume the nonaffected side as the
      predominantly used hemibody and where the overload was observed.

PMID- 21721995
TI  - Use of an abbreviated neuroscience education approach in the treatment of chronic
      low back pain: a case report.
AB  - Chronic low back pain (CLBP) remains prevalent in society, and conservative
      treatment strategies appear to have little effect. It is proposed that patients
      with CLBP may have altered cognition and increased fear, which impacts their
      ability to move, perform exercise, and partake in activities of daily living.
      Neuroscience education (NE) aims to change a patient's cognition regarding their
      pain state, which may result in decreased fear, ultimately resulting in
      confrontation of pain barriers and a resumption of normal activities. A 64-year
      old female with history of CLBP was the patient for this case report. A physical
      examination, the Numeric Pain Rating Scale (NPRS), Oswestry Disability Index
      (ODI), Fear-Avoidance Beliefs Questionnaire (FABQ), and Zung Depression Scale
      were assessed during her initial physical therapy visit, immediately after her
      first physical therapy session, and at 7-month follow-up. Treatment consisted of
      an abbreviated NE approach, exercises (range of motion, stretches, and
      cardiovascular), and aquatic therapy. She attended twice a week for 4 weeks, or 8
      visits total. Pre-NE, the patient reported NPRS = 9/10; ODI = 54%; FABQ-W =
      25/42,; FABQ-PA = 20/24, and Zung = 58. Immediately following the 75-minute
      evaluation and NE session, the patient reported improvement in all four outcome
      measures, most notably a reduction in the FABQ-W score to 2/42 and the FABQ-PA to
      1/24. At a 7-month follow-up, all outcome measures continued to be improved. NE
      aimed at decreasing fear associated with movement may be a valuable adjunct to
      movement-based therapy, such as exercise, for patients with CLBP.

PMID- 21721996
TI  - Treatment of patella alta with taping, exercise, mobilization, and functional
      activity modification: a case report.
AB  - Knee pain associated with patella alta (PA) can limit involvement in sport or
      work activities and prevent an individual from performing basic functional tasks.
      This case report describes the use of patellar taping to treat an individual with
      PA. The patient was a 56 year-old female with bilateral knee pain associated with
      PA. The focus of treatment was to decrease pain during functional activities by
      using tape to correct patella alignment. The patient was also instructed on
      specific exercises and mobilizations. The primary outcome measure was the ADL
      subscale of the Knee Outcome Survey (ADL-KOS). Initially, the patient scored a 50
      on the ADL-KOS and rated her function at 30% of normal. She demonstrated symptom
      improvement when tape was applied appropriately and was, therefore, instructed in
      tape application. At discharge, the patient scored a 56 on the ADL-KOS and rated
      her function at 70% of normal. This case demonstrates the effective use of a
      taping method for the treatment of pain associated with PA. Taping appears to be
      a safe, conservative, and cost-efficient measure to manage symptoms and to
      improve activity tolerance in this patient.

PMID- 21721997
TI  - Ankylosing spondylitis in a patient referred to physical therapy with low back
      pain.
AB  - Low back pain (LBP) is one of the most common and costly medical conditions in
      the United States; various studies have reported up to 80% of the adult
      population will experience a significant episode of LBP sometime within their
      lifetime. Although many cases of LBP are related to the musculoskeletal system
      and appropriate for the care of the physical therapist (PT), some episodes of LBP
      have a systemic cause. Thus, it is the role of the PT to ensure each patient is
      appropriate for physical therapy intervention throughout the episode of care.
      When the patient's condition is not appropriate for physical therapy
      intervention, it is the PT's responsibility to refer the patient to other medical
      professions to ensure optimal patient care. The purpose of this case report is to
      describe a patient referred to PT who was diagnosed with ankylosing spondylitis.
      The patient presented initially to physical therapy with a diagnosis of LBP.
      However, after several visits her symptoms were inconsistent with mechanical LBP
      and thus required further medical consultation.

PMID- 21721998
TI  - A qualitative study: Clinical decision making in low back pain.
AB  - Classification systems are available to subgroup patients with acute/nonspecific
      low back pain (LBP) to determine interventions. The use of classification systems
      by physical therapists (PT) has little published evidence. The aims of this study
      were to understand the process PTs use when assessing and determining
      interventions for patients with acute/nonspecific LBP in outpatient settings and
      what classification systems, if any, are used in clinical practice. Qualitative
      methods were used to investigate the decision-making process PTs use when
      managing patients with LBP. Semi-structured interviews focused on the decision
      making process of examination and intervention selection for patients with LBP.
      Findings were verified through member checking, triangulation, and audit trail.
      Thirteen PTs were included in the study. Four decision-making preferences emerged
      from the data: (1) identifying the root cause, (2) eclectic approach, (3)
      experience-based management, and (4) evidence-based management. Experience,
      education, and other aspects of the PTs' backgrounds influenced their preferred
      decision-making style, and use of resources, such as classification systems,
      varied broadly.

PMID- 21721999
TI  - The reliability and concurrent validity of scapular plane shoulder elevation
      measurements using a digital inclinometer and goniometer.
AB  - This study investigated the reliability and concurrent validity of active
      shoulder elevation in the scapular plane (scaption) using a digital inclinometer
      and goniometer. Two investigators used a goniometer and digital inclinometer to
      measure scaption on 30 asymptomatic participants in a blinded repeated measures
      design. Good reliability was present with intraclass correlation coefficients
      (ICCs) for intrarater reliability of goniometry = 0.87, intrarater digital
      inclinometry = 0.88, interrater goniometry = 0.92, and interrater digital
      inclinometry = 0.89. The minimal detectable change (MDC95) for the interrater
      analysis indicated that a change equal to or greater than 8 degrees for
      goniometry and 9 degrees for inclinometry is required to be 95% certain that the
      change is not due to intertrial variability or measurement error. The concurrent
      validity between goniometry and digital inclinometry was excellent with an ICC
      value of 0.94 for both raters. The 95% limits of agreement suggest that the
      difference between these two measurement instruments can be expected to vary by
      up to +/-11 degrees. The results support the interchangeable use of goniometry
      and digital inclinometer for measuring scaption. Clinicians and researchers
      should consider the MDC values presented when interpreting change during
      subsequent measurement sessions.

PMID- 21722000
TI  - Improved dissolution behavior of lipophilic drugs by solid dispersions: the
      production process as starting point for formulation considerations.
AB  - INTRODUCTION: Many new drug substances have low aqueous solubility which can
      cause poor bioavailability after oral administration. The application of solid
      dispersions is a useful method to increase the dissolution rate of these drugs
      and thereby improve their bioavailability. So far, several methods have been
      developed to prepare solid dispersions. To obtain a product with the desired
      attributes, both the formulation and production processes should be considered.
      AREAS COVERED: The most currently used methods to produce solid dispersions, such
      as the fusion method, hot melt extrusion, spray drying, freeze drying and
      supercritical fluid precipitation, are reviewed in this paper. In addition, the
      physicochemical characteristics of the obtained solid dispersions are discussed.
      EXPERT OPINION: Solid dispersions can be successfully prepared by simple fusion,
      hot melt extrusion, spray drying, freeze drying and supercritical fluid
      precipitation. Hot melt extrusion, spray drying and freeze drying are processes
      that can be applied for large scale production. The simple fusion method is not
      very suitable for large scale production, but is particularly suitable for
      screening formulations. The most recent method to produce sold dispersions is
      supercritical fluid precipitation. The process conditions of this method need
      extensive investigation, in particular in relationship with the selection of the
      type of carrier and/or solvent. Both processes and formulation aspects strongly
      affect the characteristics of solid dispersion products. Furthermore, application
      of crystalline solid dispersions is gaining increasing interest because they are
      thermodynamically more stable than amorphous solid dispersions.

PMID- 21722001
TI  - Criteria of gait asymmetry in patients with hip osteoarthritis.
AB  - Gait symmetry is often a goal for physiotherapy in patients with hip
      osteoarthritis and after total hip replacement. However, there is no agreement on
      criteria for pathological gait asymmetry. In this study we investigated
      discriminative abilities of trunk and footfall gait symmetry measures, and
      thereafter assessed whether a 10% cutoff value is valid as a general criterion of
      pathological gait asymmetry across measures. Anteroposterior, vertical, and
      mediolateral trunk symmetry, single support, and step length symmetry were
      obtained simultaneously by trunk accelerometry and an electronic walkway in 37
      patients with end-stage hip osteoarthritis and 56 controls. Subjects walked six
      times along a 7-meter walkway at slow, preferred, and fast speed, before data
      were normalized for gait velocity. Anteroposterior, vertical, and single support
      symmetry measures showed best discriminating abilities. The general 10% criterion
      of gait asymmetry and optimal cutoff criteria calculated for each symmetry
      measure showed approximately equal total classification ability. However, the
      optimal cutoff criteria classified a high number of controls as having
      pathological gait asymmetry. The general criterion of 10% is valid with high
      total classification ability, does not classify asymmetry in able-bodied subjects
      as pathological, and is feasible for use on individual patients in the clinic as
      well as in research.

PMID- 21722002
TI  - Assessing the port to port risk of vessel movements vectoring non-indigenous
      marine species within and across domestic Australian borders.
AB  - Biofouling of vessels is implicated as a high risk transfer mechanism of non
      indigenous marine species (NIMS). Biofouling on international vessels is managed
      through stringent border control policies, however, domestic biofouling transfers
      are managed under different policies and legislative arrangements as they cross
      internal borders. As comprehensive guidelines are developed and increased
      compliance of international vessels with 'clean hull' expectations increase,
      vessel movements from port to port will become the focus of biosecurity
      management. A semi-quantitative port to port biofouling risk assessment is
      presented that evaluates the presence of known NIMS in the source port and
      determines the likelihood of transfer based on the NIMS association with
      biofouling and environmental match between source and receiving ports. This risk
      assessment method was used to assess the risk profile of a single dredge vessel
      during three anticipated voyages within Australia, resulting in negligible to low
      risk outcomes. This finding is contrasted with expectations in the literature,
      specifically those that suggest slow moving vessels pose a high to extreme risk
      of transferring NIMS species.

PMID- 21722003
TI  - Intervention-engagement and its role in the effectiveness of stage-matched
      interventions promoting physical exercise.
AB  - Intervention-engagement has received little attention in sports medicine as well
      as research and promotion of physical exercise. The construct is important,
      however, in the understanding of why interventions work. This study aimed at
      shedding more light on the interplay of engagement and the subsequent
      effectiveness of physical exercise interventions. A three-stage model
      differentiating among nonintenders, intenders, and actors informed the
      intervention design in this study. In an Internet-based randomized controlled
      trial (RCT) with two measurement points, N = 326 participants received a stage
      matched, stage-mismatched, or control treatment. Assessed variables were goal
      setting, planning, behavior, and intervention-engagement. It was found that
      regarding goal setting, nonintenders in the stage-matched intervention and those
      who engaged highly in the stage-matched intervention improved significantly over
      time. Regarding planning, intenders in the matched condition as well as all
      actors increased their levels over time. Regarding behavior, nonintenders and
      intenders having engaged highly in the intervention improved more than those
      having engaged little. In order to help nonintenders progress on their way toward
      goal behavior, it is necessary that they engage highly in a stage-matched
      intervention. Implications for exercise promotion are that interventions should
      also aim at increasing participants' intervention-engagement.

PMID- 21722004
TI  - Estimation of injury simulation in international women's football.
AB  - This study attempted to determine the frequency of apparent injury incidents in
      women's international football and estimate what proportion was authentic.
      Broadcast recordings of 47 games from 2 tournaments were reviewed to identify
      incidents in which a player behaved as if injured. Apparent injuries were
      considered definite if a player withdrew from participation within 5 minutes or
      if bleeding was visible. Remaining incidents were considered questionable. A
      total of 270 apparent injuries were observed at a rate of 5.74/game compared with
      11.26/game previously reported in men's football. The definite injury rate was
      only 0.78/game vs. 4.96/game for questionable injuries. Definite injuries were
      associated with on-field treatment (P < 0.010), stretcher (P < 0.010), and second
      half (P = 0.022), while questionable injuries were associated with fouls (P =
      0.036), contact (P < 0.010), and being tackled (P = 0.025). Questionable injuries
      were not associated with the final third of a half or with team success.

PMID- 21722005
TI  - The effect of 1,000 km nonstop cycling on fat mass and skeletal muscle mass.
AB  - We evaluated the change in body mass including fat mass and skeletal muscle mass
      in one ultracyclist whilst cycling 1,000 km in 48 hours at a constant intensity
      of ~48% VO(2)max, corresponding to a heart rate frequency of ~105 +/- 5 bpm. A 1
      kg fat mass decrease resulted, with the largest decrease occurring between the
      12th and the 24th hour. No steady state in metabolism was observed and no regular
      decrease of subcutaneous adipose tissue resulted. This result is backed up by the
      nuclear magnetic resonance (NMR) urine analysis. Body water increase with
      simultaneous dehydration is possibly due to endocrine-induced renal water
      retention, in order to maintain metabolism processes that are required for energy
      supply and blood flow during very prolonged exercise. Both applied methods, the
      anthropometric and the bioelectrical impedance analysis, analyse fluid
      accumulation--especially in the skinfolds of the lower extremities--apparently
      incorrectly as an increase in body mass and not as an increase in fluids.

PMID- 21722006
TI  - The influence of soccer shoe design on player performance and injuries.
AB  - Although soccer is the most popular sport in the world, little research has been
      published in the field of soccer biomechanics, particularly on the importance of
      footwear for the game. The traction properties of soccer shoes on natural and
      artificial turf have been speculated to be responsible for acute and chronic
      injuries in soccer. This article reviewed the current knowledge on how soccer
      shoes influence the risk of injuries and how they may serve to improve player
      performance. Comfort is the highest priority that players want from their shoes,
      followed by traction and stability. Cleat design and arrangement are important
      shoe features that allow for fast accelerations and stops, rapid cuts, and turns.
      Soccer shoe design can influence shooting speed and, even more important for the
      game of soccer, kicking accuracy. To combine shoe characteristics for injury
      prevention and better performance will be a challenge for future research on
      optimizing soccer shoes.

PMID- 21722007
TI  - Considerations in the use of high intensity leg cycle ergometry as a test of
      muscular performance.
AB  - High intensity leg cycle ergometry is a widely used method of measuring muscular
      performance during maximal exercise. Until recently, it was deemed to be a
      predominantly lower body activity; however, there is now evidence to suggest that
      the upper body could be making a significant contribution to power output, as
      demonstrated by the intense electrical activity of the forearm musculature. As
      high intensity cycle ergometry often is used to measure performance in untrained
      cyclists it is important they are given at least two familiarisation trials to
      ensure results are both reliable and reproducible. In addition, diurnal
      variations exist during a single high intensity bout of exercise. It is likely
      these daily fluctuations are influenced by a number of biochemical and
      physiological variables. The purpose of this article is to outline factors that
      contribute to our interpretation of data following high intensity cycle
      ergometry.

PMID- 21722009
TI  - Neuroticism mediates the relationship between childhood adversity and adult sleep
      quality.
AB  - This study investigated the relationship of childhood adversity and adult sleep
      quality in 327 college students (91 males), with a mean age of 18.9 years (SD =
      2.1) and also examined whether neuroticism significantly mediated the observed
      association. Regression findings indicate that the relationship between childhood
      adversity and adult sleep quality is significant, and that there is a stronger
      association in men. Furthermore, a bootstrapping approach to testing the
      significance of the indirect effect (i.e., mediation) indicated that neuroticism
      mediated this relationship in both men and women. These data suggest that
      otherwise healthy young adults with a history of childhood adversity are at
      increased risk for sleep disturbance. Neuroticism may represent a potential
      target for change in future insomnia interventions, particularly in adults with a
      history of childhood adversity.

PMID- 21722010
TI  - Sleep problems and fatigue in chronically ill women.
AB  - The objective of this study was to understand the quality and quantity of sleep
      in women with multiple sclerosis (MS) or rheumatoid arthritis (RA), who also had
      young children, and how their sleep behaviors were associated with their fatigue.
      A cross-sectional sample of mothers with MS and RA and a well comparison group
      completed mailed surveys. Participants included 103 mothers with MS, 68 mothers
      with RA, and 91 well mothers. Mothers answered questions about their sleep,
      fatigue, pain, and depression. Women with chronic illnesses reported more
      problems going to sleep than did well women, with pain, depression, or both as
      significant covariates. Women with chronic illnesses reported that their sleep
      was interrupted less often by their children than did well women. Sleep quality
      and quantity were worse for women with RA who were experiencing a flare. Mothers
      with chronic illnesses experienced more sleep problems, which was associated with
      their pain and depression.

PMID- 21722011
TI  - Self-reported features of sleep, utilization of medical resources, and
      socioeconomic position: a Swedish population survey.
AB  - This study examined aspects of self reported qualities of sleep and daytime
      functioning attributed to sleep, including the utilization of physician
      consultations and prescription medications, and their relationships with age,
      gender, and educational attainment in the Swedish population using telephone
      interviews of 1,000 random households. Women were twice as likely to use
      hypnotics and experienced more poor quality sleep and excessive daytime
      sleepiness (EDS). Lower educational attainment was associated with twofold
      increased hypnotic use, life impacts of sleep problems, and EDS, but not
      dimensions reflecting poor quality sleep. This study demonstrates that
      educational attainment, gender, and age combine to shape both the attributions of
      the effects of sleep on wakeful functioning and patterns of using medical
      resources.

PMID- 21722012
TI  - The relative contribution of affect load and affect distress as predictors of
      disturbed dreaming.
AB  - This is the first study to empirically investigate the heuristic model of
      dysphoric dreaming proposed by Levin and Nielsen (2007) . Participants indicated
      their incidence of nightmares (NMs) and bad dreams (BDs) over 21 days, and rated
      their subsequent distress in daily dream logs. Results support the contention
      that the 2 constructs identified in the model, affect load (AL) and affect
      distress (AD), underlie NM production and are active in both the waking and
      sleeping states. As predicted, AL accounted for more unique variance to the
      prediction of incidences of disturbed dreaming (DD), whereas AD accounted for
      more unique variance to the prediction of distress over NMs and BDs. Taken
      together, these findings are consistent with Levin and Nielsen's (2007) model and
      bolster earlier findings that suggest that distress about DD remains a crucial
      component in the relation between DD frequency and waking psychopathology.

PMID- 21722013
TI  - Defining the roles of actigraphy and parent logs for assessing sleep variables in
      preschool children.
AB  - Actigraphy provides a non-invasive objective means to assess sleep-wake cycles.
      In young children, parent logs can also be useful for obtaining sleep-wake
      information. The authors hypothesized that actigraphy and parent logs were both
      equally valid instruments in healthy preschool-aged children. The authors studied
      59 children aged 3 to 5 years in full-time day care. Each child was screened for
      medical problems and developmental delays before being fitted with an actigraphy
      watch, which was worn for 1 week. Parents maintained logs of sleep and
      wakefulness during the same period, with input from day care workers. In general,
      parents overestimated the amount of nighttime sleep measured by actigraphy by 13%
      to 22% (all significant). Although there was no difference in sleep onset times,
      parents reported later rise times on the weekend and fewer nighttime awakenings.
      There was no significant difference between parent logs and actigraphy with
      regard to daytime napping. The authors conclude that parent logs are best
      utilized in assessing daytime sleep and sleep onset, whereas actigraphy should be
      used to assess nighttime sleep and sleep offset time.

PMID- 21722014
TI  - Risk for sleep-disordered breathing and home and classroom behavior in Hispanic
      preschoolers.
AB  - Pediatric sleep-disordered breathing (SDB) is known to negatively impact home and
      classroom behavior. Preschool-age Hispanic children from Spanish-speaking
      households are at elevated risk for poor school readiness. The authors used a
      multi-informant approach to assess home and preschool behavior among Hispanic
      children at risk for SDB (n = 67). Higher parent-reported SDB risk and elevated
      snoring were associated with parent- and teacher-reported problem behaviors and
      poorer teacher-reported classroom executive function among boys; elevated snoring
      was associated with internalizing behaviors among girls. Elevated snoring may be
      associated with problems related to impaired inhibitory self-control, suggesting
      the need for early intervention in order to improve school readiness among these
      a priori defined at-risk Hispanic children.

PMID- 21722015
TI  - LBP and sCD14 patterns in total hip replacement surgery performed during combined
      spinal/epidural anaesthesia.
AB  - BACKGROUND: Danger patterns and pattern recognition receptors have been targets
      in the investigation and treatment of systemic inflammatory response syndrome and
      sepsis. Lipopolysaccharide (LPS)-binding protein (LBP) presents LPS and gram
      positive bacterial cell wall products to the receptors TLR4/MD-2 and TLR2,
      respectively. Low concentrations of LBP stimulate responses to LPS and
      peptidoglycan, whereas higher concentrations inhibit these responses. Soluble
      CD14 (sCD14) presents the LBP-LPS complex to CD14-negative cells, and it
      modulates the biological activity of circulating LPS. In this study, we aimed to
      elucidate the physiological reactions to LBP and sCD14 after total hip
      replacement surgery during spinal/epidural anaesthesia. METHODS: Seven patients
      with coxarthrosis were operated upon with a total hip replacement, which is a
      defined trauma to bone and muscles in conjunction with a certain amount of blood
      loss. Venous blood samples were taken before the operation and at 1 h, 3 days and
      6 days after surgery. LBP and sCD14 were measured by conventional ELISA. To
      correct for hemodilution, each parameter was adjusted for hematocrit. A panel of
      cytokines was measured using Luminex technology to evaluate the trauma reaction.
      RESULTS: IL-6 levels peaked 24 h after the operation, whereas IL-1beta and IL-10
      levels remained unchanged. Systemic levels of LBP were increased 24 h after
      surgery, whereas sCD14 remained steady. However, the dilution-corrected sCD14
      values increased significantly, and the levels of both LBP and sCD14 peaked at
      day 3 after surgery. CONCLUSION: Aseptic trauma primes the innate immune system
      for the posttraumatic release of LBP and sCD14.

PMID- 21722016
TI  - Serum prolidase activity in patients with pulmonary tuberculosis.
AB  - AIM: To investigate serum prolidase activity (SPA) in patients with pulmonary
      tuberculosis (PTB). MATERIAL AND METHODS: Twenty-nine PTB patients and 32
      controls were included in the study. PTB patients (cavitary and non-cavitary) and
      controls were compared in terms of mean SPA. Correlations were evaluated between
      SPA and acute phase reactants. RESULTS: Mean SPA was significantly higher in PTB
      patients than in the control group. Mean SPA was significantly higher in patients
      with cavitary TB than non-cavitary TB. Mean SPA in patients with mild PTB was
      lower than patients with moderate and severe disease. We found significant
      correlations between SPA and CRP, ESR, albumin, platelet counts, HDL-cholesterol
      and LDH activity. CONCLUSION: This study has shown that PTB patients have higher
      SPA than controls. The increase in SPA might be related to tissue destruction,
      increased immunoglobulin, complement levels and increased fibroblastic activity;
      all of which are involved in the natural history of PTB.

PMID- 21722017
TI  - Erythropoietin and amyotrophic lateral sclerosis: Plasma level determination.
AB  - In amyotrophic lateral sclerosis (ALS), respiratory muscle weakness causes
      ventilatory insufficiency and tissue hypoxia, which induces a number of metabolic
      pathways, and in particular increases erythropoietin (EPO) synthesis. EPO is a
      glycoprotein with neuroprotective properties that stimulates erythropoiesis.
      Here, EPO plasma level in a large population of ALS patients, with and without
      respiratory failure, was measured. Plasma EPO level of patients with ALS (n =
      98), controls with other neuromuscular diseases (n = 58) and healthy controls (n
      = 20) has been quantified by ELISA. No significant difference was found between
      ALS patients and the two control groups. EPO level was not different between
      bulbar- and spinal-onset patients and was not correlated with disease duration or
      functional impairment. However, in the ALS group EPO level was higher in females
      (p = 0.0006) and correlated positively with age (p = 0.006). The subgroup of ALS
      patients with respiratory failure had higher plasma levels of EPO compared with
      ALS patients with preserved respiratory function (p = 0.016), but short-term non
      invasive ventilation did not change EPO level. In conclusion, EPO levels were
      found to be significantly higher in ALS patients with respiratory impairment
      representing preservation of this homeostatic mechanism.

PMID- 21722018
TI  - Hyperstable regulation of vigilance in patients with major depressive disorder.
AB  - OBJECTIVES: This study tested the hypothesis that patients with depression show
      less and later declines into lower EEG vigilance stages (different global
      functional brain states) under resting conditions than healthy controls, as
      proposed by the vigilance theory of affective disorders. METHODS: Thirty patients
      with Major Depressive Disorder (19 female; mean age: 37.2 years, SD: 12.6)
      without psychotropic medication and 30 carefully age- and sex-matched controls
      (19 female; mean age: 37.3 years, SD: 12.8) without past or present mental
      disorders underwent a 15-min resting EEG. EEG-vigilance regulation was determined
      with a computer-based vigilance classification algorithm (VIGALL, Vigilance
      Algorithm Leipzig), allowing a classification of vigilance stages A (with
      substages A1, A2 and A3), B (with substages B1 and B2/3) and C. RESULTS:
      Depressive patients spent significantly more time in the highest EEG vigilance
      substage A1, and less time in substages A2, A3 and B2/3 than controls. In
      depressive patients, a significantly longer latency until the occurrence of
      substages A2, A3 and B2/3 was observed. No significant group differences in the
      percentage of B1 segments or the latency until occurrence of B1 were found.
      CONCLUSIONS: The results confirm the hypothesis that patients with depression
      show less (and later) declines into lower EEG vigilance stages under resting
      conditions than healthy controls, and support the vigilance theory of affective
      disorders linking a hyperstable vigilance regulation to depression.

PMID- 21722019
TI  - Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic
      factor Val66Met polymorphism: meta-analysis.
AB  - OBJECTIVES: Converging evidence suggests that the brain-derived neurotrophic
      factor (BDNF) gene Val66Met polymorphism affects brain structure. Yet the
      majority of studies have shown no effect of this polymorphism on hippocampal
      volumes, perhaps due to small effect size. METHODS: We performed a meta-analysis
      of studies investigating the association between Val66Met BDNF polymorphism and
      hippocampal volumes in healthy subjects by combining standardized differences
      between means (SDM) from individual studies using random effect models. RESULTS:
      Data from 399 healthy subjects (255 Val-BDNF homozygotes and 144 carriers of at
      least one Met-BDNF allele) in seven studies were meta-analysed. Both the left and
      right hippocampi were significantly larger in Val-BDNF homozygotes than in
      carriers of at least one Met-BDNF allele (SDM = 0.41, 95% Confidence Interval =
      0.20; 0.62, z = 3.86, P = 0.0001; SDM = 0.41; 95% Confidence Interval = 0.20;
      0.61, z = 3.81, P = 0.0001, respectively), with no evidence of publication bias.
      CONCLUSIONS: Healthy carriers of BDNF gene Val66Met polymorphism show bilateral
      hippocampal volume reduction. The effect size was small, but the same direction
      of effect was seen in all meta-analyzed studies. The association with the BDNF
      gene Val66Met polymorphism makes hippocampal volume a potential candidate for an
      endophenotype of disorders presenting with reduced hippocampal volumes.

PMID- 21722020
TI  - Exponential modeling of human frequency-following responses to voice pitch.
AB  - OBJECTIVE: Recent studies have shown that the frequency-following response (FFR)
      to voice pitch can be a useful method to evaluate the signal-processing
      mechanisms and neural plasticity in the human brainstem. The purpose of this
      study was to examine the quantitative properties of the FFR trends with an
      exponential curve-fitting model. DESIGN: FFR trends obtained with increasing
      number of sweeps (up to 8000 sweeps) at three stimulus intensities (30, 45, and
      60 dB nHL) were fit to an exponential model that consisted of estimates of
      background noise amplitude, asymptotic response amplitude, and a time constant.
      Five objective indices (Frequency Error, Slope Error, Tracking Accuracy, Pitch
      Strength and RMS Ratio) were used to represent different perspectives of pitch
      processing in the human brainstem. STUDY SAMPLE: Twenty-three native speakers (16
      males; age = 24.7 +/- 2.1 years) of Mandarin Chinese were recruited. RESULTS: The
      results demonstrated that the exponential model provided a good fit (r(2) = 0.89
      +/- 0.10) to the FFR trends with increasing number of sweeps for the five
      objective indices. CONCLUSIONS: The exponential model, combined with the five
      objective indices, can be used for difficult-to-test patients and may prove to be
      useful as an assessment and diagnostic method in both clinical and basic research
      efforts.

PMID- 21722021
TI  - Awareness of social and emotional functioning in people with early-stage dementia
      and implications for carers.
AB  - OBJECTIVES: This study explores the extent to which awareness of social and
      emotional function is reduced in early-stage dementia and whether this relates to
      the quality of life of the person with dementia (PwD), the quality of the
      relationship between the PwD and carer and carer stress. METHOD: Ninety-seven
      participants with a diagnosis of Alzheimer's, vascular or mixed dementia rated
      their social functioning using the Socio-Emotional Questionnaire (SEQ). Carers
      provided parallel ratings, allowing calculation of discrepancy scores used to
      index awareness. Neuropsychiatric symptoms, PwD quality of life, the perceived
      quality of the relationship for both partners and carer stress were also
      measured. RESULTS: Factor analysis of the SEQ indicated three domains of social
      functioning: emotional recognition and empathy (ERE), social relationships (SR)
      and prosocial behaviour (PB). For PwD unawareness was related to cognitive
      dysfunction and psychiatric disturbance, but not to quality of life or quality of
      relationship. Lower awareness was associated with greater carer stress and poorer
      perceived quality of relationship. CONCLUSION: Lack of awareness of social
      functioning had important implications for relationship quality and levels of
      carer stress.

PMID- 21722022
TI  - Motivators of enrolment in HIV vaccine trials: a review of HIV vaccine
      preparedness studies.
AB  - HIV vaccine preparedness studies (VPS) are important precursors to HIV vaccine
      trials. As well, they contribute to an understanding of motivators and barriers
      for participation in hypothetical HIV vaccine trials. Motivators can take the
      form of altruism and a desire for social benefits. Perceived personal benefits,
      including psychological, personal, and financial well-being, may also motivate
      participation. The authors performed a systematic review of HIV VPS using the
      Cochrane Database for Systematic Reviews, Medline, PubMed, Embase, and Google
      Scholar. The authors independently searched the literature for individual HIV VPS
      that examined motivators of participation in a hypothetical HIV vaccine trial,
      using the same search strategy. As the denominators employed in the literature
      varied across studies, the denominators were standardized to the number of
      respondents per survey item, regardless of their willingness to participate (WTP)
      in an HIV vaccine trial. The authors retrieved eight studies on social benefits
      (i.e., altruism) and 11 studies on personal benefits conducted in the
      Organization for Economic Co-operation and Development (OECD) countries, as well
      as 19 studies on social benefits and 20 studies on personal benefits in the non
      OECD countries. Various different forms of altruism were found to be the major
      motivators for participation in an HIV vaccine trial in both the OECD and the non
      OECD countries. In a large number of studies, protection from HIV was cited as a
      personal motivator for participation in a hypothetical HIV vaccine trial in the
      OECD and the non-OECD countries. Knowledge of motivators can inform and target
      recruitment for HIV vaccine trials, although it must be remembered that
      hypothetical motivators may not always translate into motivators in an actual
      vaccine trial.

PMID- 21722023
TI  - Dementia, diabetes and family caregiving.

PMID- 21722024
TI  - Do childhood callous-unemotional traits drive change in parenting practices?
AB  - This study examined the relationship between callous-unemotional (CU) traits and
      parenting practices over time in a mixed-sex community cohort (N = 1,008; 52.6%
      boys), aged 3 to 10 years (M = 6.5, SD = 1.3). Measures of CU traits,
      externalizing psychopathology, parenting practices, and socioeconomic risk
      factors were collected at baseline, and parenting practices and CU traits were
      reassessed at 12-month follow-up. CU traits uniquely accounted for change in
      three domains of parenting (inconsistent discipline, punishment, and parental
      involvement). Likewise, multiple domains of parenting (positive parenting,
      parental involvement, and poor monitoring/supervision) uniquely predicted change
      in CU traits. These seemingly bidirectional dynamics between CU traits and
      parenting were found to be largely moderated by child age and sex. Results
      partially replicate previous findings regarding the association between quality
      of parenting and prospective change in CU traits, and provide initial evidence
      that CU traits disrupt parenting practices over time.

PMID- 21722025
TI  - Patterns and predictors of adolescent academic achievement and performance in a
      sample of children with attention-deficit/hyperactivity disorder.
AB  - The current study examined predictors of academic achievement, measured by
      standardized test scores, and performance, measured by school grades, in
      adolescents (Mn age = 16.8) who met diagnostic criteria for Attention
      Deficit/Hyperactivity Disorder (ADHD)-Combined type in early childhood (Mn age =
      8.5; N = 579). Several mediation models were also tested to determine whether
      ADHD medication use, receipt of special education services, classroom
      performance, homework completion, or homework management mediated the
      relationship between symptoms of ADHD and academic outcomes. Childhood predictors
      of adolescent achievement differed from those for performance. Classroom
      performance and homework management mediated the relationship between symptoms of
      inattention and academic outcomes.

PMID- 21722026
TI  - The impact of attention-deficit/hyperactivity disorder on preadolescent
      adjustment may be greater for girls than for boys.
AB  - Whether gender differences exist in the impairment associated with attention
      deficit/hyperactivity disorder (ADHD) is still largely unknown, because most
      samples have few affected girls or include only one sex. The current study
      evaluated whether ADHD affects adjustment differently for girls than boys in a
      population-based cohort of 11-year-olds (520 girls, 478 boys). Those with a DSM
      IV diagnosis of ADHD (predominantly inattentive, hyperactive-impulsive, or
      combined) were compared to those without ADHD on teacher, parent, and child
      reports of academics, peer relationships, self-concept, clinical symptoms, and
      treatment. Although boys and girls with ADHD experienced difficulties in all
      areas, girls with ADHD, especially the inattentive subtype, were more negatively
      affected in academics and peer relationships. Inattentive girls were less popular
      and more likely to be bullied than girls without ADHD, whereas inattentive boys
      were not. The social isolation experienced by many girls with ADHD deserves
      greater attention.

PMID- 21722027
TI  - A discrete choice conjoint experiment to evaluate parent preferences for
      treatment of young, medication naive children with ADHD.
AB  - The current study examined treatment preferences of 183 parents of young (average
      age = 5.8 years, SD = 0.6), medication naive children with ADHD. Preferences were
      evaluated using a discrete choice experiment in which parents made choices
      between different combinations of treatment characteristics, outcomes, and costs.
      Latent class analysis yielded two segments of parents: (a) medication avoidant
      parents constituted 70.5% of the sample whose treatment decisions were strongly
      influenced by a desire to avoid medication, and (b) outcome oriented parents
      constituted 29.5% of the sample whose treatment decisions were most influenced by
      a desire for positive treatment outcomes. Parents in the outcome oriented segment
      were more stressed and depressed, had lower socioeconomic status and education,
      were more likely to be single parents, and had more disruptive and impaired
      children. Simulations predicted that parents would prefer treatments with
      behavior therapy over treatments with stimulant medication only.

PMID- 21722028
TI  - Influence of treatment for disruptive behavior disorders on adrenal and gonadal
      hormones in youth.
AB  - The study examined whether psychosocial intervention for children diagnosed with
      a disruptive behavior disorder (DBD; n = 84) changed concentrations of cortisol
      and testosterone across a 3-year follow-up when compared to a matched,
      nonclinical, healthy comparison (HC; n = 69) group. Boys and girls (6-11 years)
      with a DBD were randomly assigned to one of two arms of a multimethod
      intervention. Hierarchical linear modeling revealed that children undergoing
      psychosocial intervention for a DBD experienced a significant decline in diurnal
      cortisol change over time (p < .05) when compared to the HC condition. Boys with
      a DBD diagnosis had significantly lower mean cortisol concentrations prior to
      treatment (p < .05) and showed a significantly steeper increase in mean cortisol
      over time (p < .05) when compared to HC boys. Treatment effects for diurnal
      cortisol change were replicated in the boys-only analysis. No treatment effects
      were noted for testosterone in either analysis.

PMID- 21722029
TI  - Interaction of 5-HTTLPR and idiographic stressors predicts prospective depressive
      symptoms specifically among youth in a multiwave design.
AB  - 5-HTTLPR, episodic stressors, depressive and anxious symptoms were assessed
      prospectively (child and parent report) every 3 months over 1 year (5 waves of
      data) among community youth ages 9 to 15 (n = 220). Lagged hierarchical linear
      modeling analyses showed 5-HTTLPR interacted with idiographic stressors
      (increases relative to the child's own average level over time), but not
      nomothetic stressors (higher stress exposure relative to the sample), to predict
      prospective elevations in depressive, but not anxious, symptoms. Youth with
      copies of the S or L(G) alleles of 5-HTTLPR, who experienced more stressors
      relative to their typical level, exhibited prospective increases in depressive
      symptoms over time. These findings suggest that 5-HTTLPR confers susceptibility
      to depression via stress reactivity.

PMID- 21722030
TI  - A prospective study investigating the impact of school belonging factors on
      negative affect in adolescents.
AB  - School belonging, measured as a unidimensional construct, is an important
      predictor of negative affective problems in adolescents, including depression and
      anxiety symptoms. A recent study found that one such measure, the Psychological
      Sense of School Membership scale, actually comprises three factors: Caring
      Relations, Acceptance, and Rejection. We explored the relations of these factors
      with negative affect in a longitudinal study of 504 Australian Grade 7 and 8
      students. Each school belonging factor contributed to the prediction of negative
      affect in cross-sectional analyses. Scores on the Acceptance factor predicted
      subsequent negative affect for boys and girls, even controlling for prior
      negative affect. For girls, the Rejection factor was also significant in the
      prospective analysis. These findings have implications for the design of
      interventions and are further confirmation that school belonging should be
      considered a multidimensional construct.

PMID- 21722031
TI  - The effects of rumination on the timing of maternal and child negative affect.
AB  - The current study examined whether rumination serves as a moderator of the
      temporal association between maternal and child negative affect. Participants
      included 88 mothers with a history of major depressive episodes and their 123
      children. During an initial assessment, mothers and their children completed
      measures assessing negative affect and children completed a measure assessing the
      tendency to ruminate in response to such symptoms. Every 6 weeks for the
      subsequent year, mothers and their children completed measures assessing negative
      affect. Consistent with hypotheses, children with a ruminative response style
      were more likely than other children to report elevations in negative affect when
      their mothers' level of negative affect increased over time. Neither child gender
      nor mothers' current clinical depression status moderated the association between
      child rumination and maternal negative affect.

PMID- 21722032
TI  - Longitudinal relations between depressive symptoms and externalizing behavior in
      adolescence: moderating effects of maltreatment experience and gender.
AB  - Among the explanations for the high rates of co-occurrence between depressive
      symptoms and externalizing behavior is the possibility of direct causal
      associations between the two symptom groups. However, the mechanisms by which co
      occurrence arises may not be the same across etiologically significant variables.
      A gender-balanced sample of 303 adolescents (ages 9-12 at the first assessment)
      with carefully assessed histories of maltreatment experience and 151
      demographically matched nonmaltreated adolescents were assessed over the period
      of 1 year. Multiple-group cross-lagged panel analyses assessed the equivalence of
      longitudinal relations between depressive symptoms and externalizing behavior for
      gender/maltreatment status groups. Consistent with previous findings, the results
      suggest that girls, particularly maltreated girls, who exhibit early
      externalizing behavior are at high risk for the development of subsequent
      depressive symptoms.

PMID- 21722033
TI  - An effectiveness study of a culturally enriched school-based CBT anxiety
      prevention program.
AB  - Anxiety disorders are prevalent in the school-aged population and are present
      across cultural groups. Scant research exists on culturally relevant prevention
      and intervention programs for mental health problems in the Aboriginal
      populations. An established cognitive behavioral program, FRIENDS for Life, was
      enriched to include content that was culturally relevant to Aboriginal students.
      Students (N = 533), including 192 students of Aboriginal background, participated
      in the cluster randomized control study. Data were collected three times over 1
      year. A series of multilevel models were conducted to examine the effect of the
      culturally enriched FRIENDS program on anxiety. These analyses revealed that the
      FRIENDS program did not effectively reduce anxiety for the total sample or for
      Aboriginal children specifically. However, all students, regardless of
      intervention condition, Aboriginal status, or gender, reported a consistent
      decrease in feelings of anxiety over the 6-month study period.

PMID- 21722034
TI  - The relation between insecure attachment and child anxiety: a meta-analytic
      review.
AB  - Attachment theory suggests that children's attachment insecurity plays a key role
      in the development of anxiety. In the present study we evaluated the empirical
      evidence for the link between insecure attachment and anxiety from early
      childhood to adolescence. A meta-analysis of 46 studies, from 1984 to 2010,
      including 8,907 children, was conducted. The results show an overall effect size
      of r = .30, indicating that attachment is moderately related to anxiety.
      Moderator analyses indicated that ambivalent attachment showed the strongest
      association with anxiety. Further, the relation was stronger during adolescence,
      when attachment and anxiety were measured through questionnaires, when the
      informant was the child, when attachment was measured as internal working model,
      in cross-sectional studies, and in studies conducted in Europe. No difference was
      found between studies that measured anxiety as symptoms or as a disorder, and
      when different kinds of anxiety were considered.

PMID- 21722035
TI  - Testing the adaptation to poverty-related stress model: predicting
      psychopathology symptoms in families facing economic hardship.
AB  - This study tested the Adaptation to Poverty-related Stress Model and its proposed
      relations between poverty-related stress, effortful and involuntary stress
      responses, and symptoms of psychopathology in an ethnically diverse sample of low
      income children and their parents. Prospective Hierarchical Linear Modeling
      analyses conducted with 98 families (300 family members: 136 adults, 82
      adolescents and preadolescents, 82 school-age children) revealed that, consistent
      with the model, primary and secondary control coping were protective against
      poverty-related stress primarily for internalizing symptoms. Conversely,
      disengagement coping exacerbated externalizing symptoms over time. In addition,
      involuntary engagement stress responses exacerbated the effects of poverty
      related stress for internalizing symptoms, whereas involuntary disengagement
      responses exacerbated externalizing symptoms. Age and gender effects were found
      in most models, reflecting more symptoms of both types for parents than children
      and higher levels of internalizing symptoms for girls.

PMID- 21722036
TI  - Placental IDO and oxidative damage in pre-eclampsia: fresh chicken or fresh eggs?
      Preface.

PMID- 21722037
TI  - Aquaculture fouling: Efficacy of potassium monopersulphonate triple salt based
      disinfectant (Virkon(r) Aquatic) against Ciona intestinalis.
AB  - With the increasing spread of invasive marine species and their detrimental
      effects on aquaculture operations globally, mitigation strategies need to be
      optimized to mitigate economic impacts. The efficacy of a potassium
      monopersulphonate triple salt based disinfectant used in the aquaculture industry
      (Virkon(r) Aquatic at 0.5-5%) was evaluated against the solitary tunicate Ciona
      intestinalis, as well as the susceptibility of three different age groups of C.
      intestinalis to the treatment and the effect of the disinfectant on mussel
      mortality. Younger C. intestinalis were most affected by all treatments, and
      almost all immersion applications significantly decreased the biomass of C.
      intestinalis compared to untreated plates. Disinfectant solutions of >= 1%
      reduced biomass below pre-treatment levels. Mussel mortality was low, especially
      for solutions <3%. C. intestinalis should be treated 4 weeks post-settlement to
      maximize antifouling treatment effects. Immersion in 3% disinfectant for 30 s
      reduced the biomass of C. intestinalis by up to 89% and would be feasible in
      field applications using existing treatment equipment.

PMID- 21722038
TI  - A caregiver perspective of how Alzheimer's disease and related disorders affect
      couple intimacy.
AB  - OBJECTIVES: Alzheimer's disease and related disorders (ADRD) pose a potential
      threat to the interpersonal and intimate relationships in couples. The objective
      of this study was to understand the lived experiences of individuals with a
      spouse suffering from ADRD and how this diagnosis affects intimacy within these
      marital relationships. METHOD: This qualitative study used a phenomenological
      approach to capture the lived experiences of caregivers of ADRD individuals. A
      total of 10 interviews were conducted, with six participants recruited from a
      neurology clinic and four participants drawn from support groups. Structured
      interviews with open-ended questions were conducted, with thematic units derived
      from the interview analysis. RESULTS: All participants reported some strain in
      the ADRD relationship, with different aspects of the disease affecting closeness
      and connection within the couple. The quality of the marital relationship prior
      to diagnosis impacted every participant in some fashion as well as having to
      adjust to ADRD related behaviors. Outside effects on the relationship, coping
      with the disease and degree of intimacy were additional themes reported from the
      interviews, with positive and negative attributes given to these themes.
      CONCLUSION: Although the caregiving role can be difficult for a spouse, it does
      not mean that the ADRD has to always negatively impact the marital relationship.
      Understanding the role that intimacy can play for these couples and how it might
      contribute to coping strategies for couples affected by ADRD can be a powerful
      adjunct to other treatments available.

PMID- 21722039
TI  - Factors associated with depressive symptoms among older adults living alone: an
      analysis of sex difference.
AB  - OBJECTIVES: The aim of this study was to explore the prevalence of depressive
      symptoms and the risk factors that correlated with depressive symptoms among
      elders living alone. METHODS: A cross-sectional design was implemented. The
      sample consisted of 117 women and 75 men aged 65 and older who living alone in
      Tainan, Taiwan. The Chinese version of Center for Epidemiological Studies
      Depressive Symptoms Scale was adopted to assess depressive symptoms. Logistic
      regression analyses were employed to determine the risk factors of depressive
      symptoms in the elderly women and men living alone. RESULTS: Results of this
      study showed that the elderly women had a 1.6-fold greater prevalence of
      depressive symptoms than did men. Women who were aged 85 and above, and less
      social support, had a significantly higher occurrence rate of depressive
      symptoms. The risk factors for depressive symptoms in elderly men living alone
      included educational level, religious beliefs, self-rated health status, number
      of chronic illnesses, and social support. CONCLUSIONS: Healthcare providers
      should reflect the sex difference on risk factors of depressive symptoms when
      planning mental health services for the elderly population.

PMID- 21722040
TI  - Alkaloids and flavonoids of Argemone mexicana.
AB  - A new protopine alkaloid, protomexicine and a new isoflavonoid, mexitin, together
      with 8-methoxydihydrosanguinarine, 13-oxoprotopine, rutin and quercetrin have
      been isolated from the aerial part of the methanolic extract of Argemone
      mexicana. The structures of these compounds have been established by various
      spectral data. The structure of protomexicine was further confirmed by
      heteronuclear multiple bond correlation experiment. Protomexicine and mexitin are
      new compounds, and other compounds are first reported from A. mexicana and genus
      Argemone.

PMID- 21722041
TI  - Effects of personal meaning among patients in primary and specialized care:
      associations with psychosocial and physical outcomes.
AB  - Personal meaning is thought to serve as an important resource among individuals
      adapting to the demands of illness. However, some work in this area has been
      marked by vague conceptualization, or use of assessment instruments that are
      confounded by well-being. This investigation evaluated relationships between
      psychosocial and physical outcomes and one theoretically important dimension of
      attained global meaning - perceptions of life purpose and commitment. Study 1
      evaluated 175 patients followed in a primary care gynaecological practice. Study
      2 assessed 104 cancer patients in a specialized stem cell transplantation centre.
      In both samples, personal meaning was concurrently associated with reduced
      emotional distress, enhanced coping efficacy, and closer intimate relationships,
      after controlling for social desirability bias and relevant demographic and
      medical covariates. Associations with lower distress and improved coping efficacy
      remained significant after additionally controlling for other psychosocial
      resource variables (i.e. social support, religiousness, emotional control).
      Personal meaning appears to be independently related to concurrent psychosocial
      adjustment in a range of medical settings.

PMID- 21722044
TI  - The impact of Cognitive Stimulation Therapy groups on people with dementia: views
      from participants, their carers and group facilitators.
AB  - OBJECTIVES: Cognitive Stimulation Therapy (CST) can lead to significant
      improvements in cognitive function and quality of life for people with dementia.
      This study sought to investigate whether improvements found in clinical trials
      were also noted by people with dementia, their carers and group facilitators in
      everyday life. METHOD: Qualitative interviews and focus groups were conducted
      with people attending CST groups, their carers and the group facilitators. Data
      were recorded and transcribed, before being analysed using Framework Analysis.
      RESULTS: Two main themes emerged, 'Positive experiences of being in the group'
      and 'Changes experienced in everyday life', along with seven sub-themes. The
      overall experience of attending CST was seen as being emotionally positive and
      most participants reported some cognitive benefits. CONCLUSIONS: The findings
      lend further support to previous quantitative findings, as well as providing
      information about the personal experience of CST.

PMID- 21722045
TI  - Self-report of psychological function among OEF/OIF personnel who also report
      combat-related concussion.
AB  - MMPI-2 RF profiles of 128 U.S. soldiers and veterans with history of concussion
      were examined. Participants evaluated in forensic (n = 42) and clinical (n = 43)
      settings showed significantly higher validity and clinical elevations relative to
      a research group (n = 43). In the full sample, a multivariate GLM identified main
      effects for disability claim status and Axis I diagnosis across numerous MMPI-2
      RF scales. Participants with co-morbid PTSD and concussion showed significant
      Restructured Clinical and Specific Problem scale elevations relative to those
      without Axis I diagnosis. Participants with PTSD and active disability claims
      were especially prone to elevate on FBS/FBS-r and RBS. Implications for
      neuropsychologists who routinely administer the MMPI-2/RF in the context of
      combat-related concussion are discussed.

PMID- 21722047
TI  - Altered depth perception is associated with presence of schizotypal personality
      traits.
AB  - INTRODUCTION: Impaired depth perception, a fundamental aspect of early visual
      processing, has been shown in patients with schizophrenia suggesting a
      disturbance to magnocellular and possibly parvocellular pathways. Despite some
      evidence showing visual-perceptive deficits in people with schizotypal
      personality traits (SPT), depth perception has not been evaluated in these
      subjects. METHODS: 12 clinically healthy schizotypy and 17 control participants
      were examined using a novel stereoscopic depth perception task. A mixed ANOVA
      design considered the Group (SPT/control) as independent factor, and trial Block
      (BD/BD+/BD-) and target Condition (SDSS/SDDS/DDSS/DDDS) were considered as
      repeated measures. RESULTS: Schizotypal participants were not significantly
      different to controls on simple judgements of depth but demonstrated a subtle
      impairment in perceiving binocular depth when performing high difficulty
      judgements. CONCLUSIONS: The presence of subtle depth perception problems in
      schizotypal subjects, similar but less marked than those of schizophrenia
      patients, may suggest a less pervasive disturbance of early information
      processing. If so, such deficits could be considered as innate neurological
      changes that may occur in people vulnerable for schizophrenia, thus with the
      potential to be a novel intermediate phenotype.

PMID- 21722048
TI  - Determination of typical patterns from strongly varying signals.
AB  - Forces measured in human joints vary considerably when an activity such as
      walking is carried out by different subjects or when it is repeated. 'Typical'
      standardised force-time patterns are needed to test and improve joint implants.
      Mechanically most important for their endurance are the magnitudes and times of
      force maxima and minima. They should equal the arithmetic means from the single
      measurements. Similar problems exist when evaluating other strongly varying
      signals, as in gait analysis. The new method to calculate typical signals (TSs)
      enhances existing dynamic time warping (DTW) procedures. It allows us to combine
      any number of signals. The sequence of input signals--used for calculating the TS
      -has only a minor influence. The accuracy of the method was tested numerically on
      signals for which the typical patterns could be defined exactly, and also on real
      joint forces that varied to different extents.

PMID- 21722049
TI  - Contribution of pastimes and testing strategies to the performance of healthy
      volunteers on cognitive tests.
AB  - Clinicians routinely query factors known to impact cognitive test scores,
      including age and education. However, without data delineating the impact of less
      frequently tracked variables, clinicians are limited to educated inferences about
      their effect. We explored the relationship of demographics, pastimes, and
      strategies with cognitive scores in a sample of 499 healthy young volunteers. As
      expected, age, education, ethnicity, and native language were strongly associated
      with most tests, while gender and dysphoria were associated with only some.
      Interestingly, pastimes such as playing number games and word games, and doing
      activities similar to the tests, were strongly associated with many measures, and
      testing strategies with almost all. Importantly, at least an additional 50% of
      the variation in Digit Span Backward and Animals scores was explained by adding
      covariates about pastimes and strategies to demographic covariates. These results
      support the utility of querying these elements.

PMID- 21722050
TI  - Agency affects adults', but not children's, guessing preferences in a game of
      chance.
AB  - Adults and children have recently been shown to prefer guessing the outcome of a
      die roll after the die has been rolled (but remained out of sight) rather than
      before it has been rolled. This result is contrary to the predictions of the
      competence hypothesis (Heath & Tversky, 1991 ), which proposes that people are
      sensitive to the degree of their relative ignorance and therefore prefer to guess
      about an outcome it is impossible to know, rather than one that they could know,
      but do not. We investigated the potential role of agency in guessing preferences
      about a novel game of chance. When the experimenter controlled the outcome, we
      replicated the finding that adults and 5- to 6-year-old children preferred to
      make their guess after the outcome had been determined. For adults only, this
      preference reversed when they exerted control over the outcome about which they
      were guessing. The adult data appear best explained by a modified version of the
      competence hypothesis that highlights the notion of control or responsibility. It
      is proposed that potential attributions of blame are related to the guesser's
      role in determining the outcome. The child data were consistent with an
      imagination-based account of guessing preferences.

PMID- 21722051
TI  - Reducing the probability of false positives in malingering detection of Social
      Security disability claimants.
AB  - The Symptom Validity Scale (SVS) for low-functioning individuals (Chafetz,
      Abrahams, & Kohlmaier, 2007) employs embedded indicators within the Social
      Security Psychological Consultative Examination (PCE) to derive a score validated
      for malingering against two criterion tests: Test of Memory Malingering (TOMM)
      and Medical Symptom Validity Test (MSVT). When any symptom validity test is used
      with Social Security claimants there is a known rate of mislabeling (1
      specificity), essentially calling a performance biased (invalid) when it is not,
      also known as a false-positive error. The great costs of mislabeling an honest
      claimant necessitated the present study, designed to show how multiple positive
      findings reduce the potential for mislabeling. This study utilized a known-groups
      design to address the impact of using multiple embedded indicators within the SVS
      on the diagnostic probability of malingering. Using four SVS components,
      Sequence, Ganser, and Coding errors, along with Reliable Digit Span (RDS), the
      positive predictive power was computed directly or by the chaining of likelihood
      ratios. The posterior probability of malingering increased from one to two to
      three failed indicators. With three failed indicators, there were essentially no
      false positive errors, and the total SVS score was in the range consistent with
      Definite Malingering, as shown in Chafetz et al. (2007). Thus, in a typical PCE
      when an examiner might have only a few embedded indicators, more confidence in a
      diagnosis of malingering might be obtained with a finding of multiple failures.

PMID- 21722052
TI  - The benefits of emotional expression for math performance.
AB  - This study investigated the effects of emotional expression on actual and
      perceived math performance. Female participants were either asked to express
      their emotions or given no special instructions before taking a math test under
      stereotype threat or no stereotype threat conditions. Participants in the
      emotional expression condition performed better on the math test than
      participants in the control condition. Under stereotype threat, participants in
      the emotional expression condition believed they performed better on the math
      test. Emotional expression appears not only to have health benefits (e.g.,
      Pennebaker, 1997), but academic benefits as well, including for stereotyped
      threatened individuals.

PMID- 21722053
TI  - A pilot study exploring the contribution of working memory to "jumping to
      conclusions" in people with first episode psychosis.
AB  - INTRODUCTION: People with delusional beliefs "jump to conclusions" (JTC). This
      finding is well replicated. However, there is only limited exploration of the
      factors that might lead a person to JTC. The aim of the present study was to
      explore the contribution of working memory processes (WM) and IQ to hasty
      decision making and to investigate the stability of this bias over time. METHODS:
      A single group cross-sectional design was utilised. The study was conducted in 2
      phases: (1) an initial screening phase and (2) an experimental phase whereby we
      explored and tested hypotheses regarding the cognitive origins of the JTC bias.
      In Study 1, participants completed the beads task as well as measures of mood and
      symptoms. In Study 2, the same participants repeated the beads task, and
      completed a battery of neuropsychological tests designed to assess different
      facets of WM and IQ. RESULTS: In most cases, "jumpers" were indistinguishable
      from "nonjumpers" in terms of their neuropsychological profiles. The only
      exception to this pattern was for visual working memory, in which "jumpers"
      performed better than "nonjumpers". In terms of the temporal stability of the JTC
      bias, 8 individuals (out of the 29) effectively switched from being "jumpers" at
      T1 to "nonjumpers" at T2. CONCLUSIONS: This study casts doubt on reduced global
      WM as an explanation of JTC. Rather it may be that the differences in reasoning
      are related to the manipulation of visual material and do not extend to other
      areas of neuropsychological functioning. However, as our sample is small it may
      be underpowered to detect important differences. Future work is therefore needed
      to replicate these findings.

PMID- 21722055
TI  - Contraceptive practice, unwanted pregnancies and induced abortion in Southwest
      Nigeria.
AB  - Despite widespread awareness of and access to modern contraception, high rates of
      unwanted pregnancies and abortions still persist in many parts of the world, even
      where abortion is legally restricted. This article explores perspectives on
      contraception and abortion, contraceptive decision-making within relationships,
      and the management of unplanned pregnancies. It presents findings from an
      exploratory qualitative study based on 17 in-depth interviews and 6 focus group
      discussions conducted in 2 locations in Nigeria in 2006. The results suggest that
      couples do not practice contraception consistently because of perceived side
      effects and partner objections. Abortion is usually resorted to because pregnancy
      was unwanted due to incomplete educational attainment, economic hardship,
      immaturity, close pregnancy interval, and social stigma. Males usually have
      greater influence in contraceptive-decision making than females. Though induced
      abortion is negatively viewed in the community, it is still common, and women
      usually patronise quacks to obtain such services. An abortion experience can
      change future views and decisions towards contraception. Family planning
      interventions should include access to and availability of adequate family
      planning information. Educational campaigns should target males since they play
      an important role in contraceptive decision-making.

PMID- 21722056
TI  - Better elementary number processing in higher skill arithmetic problem solvers:
      evidence from the encoding step.
AB  - This paper addresses the relationship between basic numerical processes and
      higher level numerical abilities in normal achieving adults. In the first
      experiment we inferred the elementary numerical abilities of university students
      from the time they needed to encode numerical information involved in complex
      additions and subtractions. We interpreted the shorter encoding times in good
      arithmetic problem solvers as revealing clearer or more accessible
      representations of numbers. The second experiment shows that these results cannot
      be due to the fact that lower skilled individuals experience more maths anxiety
      or put more cognitive efforts into calculations than do higher skilled
      individuals. Moreover, the third experiment involving non-numerical information
      supports the hypothesis that these interindividual differences are specific to
      number processing. The possible causal relationships between basic and higher
      level numerical abilities are discussed.

PMID- 21722057
TI  - Processing temporary syntactic ambiguity: the effect of contextual bias.
AB  - This paper reports two experiments using sentences with a temporary ambiguity
      between a direct object and a sentence complement analysis that is resolved
      toward the normally preferred direct object analysis. Postverbal noun phrases in
      these sentences could be ambiguously attached as either a direct object or the
      subject of a sentence complement, whereas in unambiguous versions of the
      sentences the subcategorization of the verb forced the direct object
      interpretation. Participants read these sentences in relatively long paragraph
      contexts, where the context supported the direct object analysis ("preferred"),
      supported the sentence complement analysis ("unpreferred"), or provided
      conflicting evidence about both analyses ("conflicting"). Self-paced reading
      times for ambiguous postverbal noun phrases were almost equivalent to the reading
      times of their unambiguous counterparts, even in unpreferred and conflicted
      context conditions. However, time to read a following region, which forced the
      direct object interpretation, was affected by the interaction of verb
      subcategorization ambiguity and contextual support. The full pattern of results
      do not fit well with either an unelaborated single-analysis ("garden path") model
      or a competitive constraint-satisfaction model, but are consistent with a race
      model in which multiple factors affect the speed of constructing a single initial
      analysis.

PMID- 21722058
TI  - Discriminating between the effects of valence and salience in the Implicit
      Association Test.
AB  - The Implicit Association Test (IAT) is the most widely used indirect measure of
      attitudes in social psychology. It has been suggested that artefacts such as
      salience asymmetries and familiarity can influence performance on the IAT. Chang
      and Mitchell  (2009)  proposed that the ease with which IAT stimuli are
      classified (classification fluency) is the common mechanism underlying both of
      these factors. In the current study, we investigated the effect of classification
      fluency on the IAT and trialled a measure-the split IAT-for dissociating between
      the effects of valence and salience in the IAT. Across six experiments, we
      examined the relationship between target classification fluency and salience
      asymmetries in the IAT. In the standard IAT, the more fluently classified target
      category was, all else being equal, compatible with pleasant attributes over
      unpleasant attributes. Furthermore, the more fluently classified target category
      was more easily classified with the more salient attribute category in the split
      IAT, independent of evaluative associations. This suggests that the more fluently
      classified category is also the more salient target category.

PMID- 21722059
TI  - On the influence of affective states on intuitive coherence judgements.
AB  - Recent research has shown that coherence judgements of semantically related word
      triads are facilitated by a subtle positive response triggered by their increased
      fluency of processing. Such positive affective response serves as a cue
      indicating semantic coherence. However, we argue that the fluency of processing
      is not the only source of affective response that can influence intuitive
      judgements. The present study investigated differential influences of mood and
      affective valence of solution words on intuitive coherence judgements. We show
      that affective cues resulting from processing fluency can be strengthened or
      weakened by inducing positive or negative affective response through the
      activation of solutions to semantically coherent triads. Also, mood is shown to
      impact the breadth of activated associations therefore affecting not only
      judgements of semantic coherence but also solvability of word triads. We discuss
      the implications of our findings for how people might form intuitive judgements
      of semantic coherence.

PMID- 21722060
TI  - Facilitation versus inhibition in the masked priming same-different matching
      task.
AB  - In the past years, growing attention has been devoted to the masked priming same
      different task introduced by Norris and Kinoshita ( 2008 , Journal of
      Experimental Psychology: General). However, a number of researchers have raised
      concerns on the nature of the cognitive processes underlying this task-in
      particular the suspicion that masked priming effects in this task are mostly
      inhibitory in nature and may be affected by probe-prime contingency. To examine
      the pattern of facilitative/inhibitory priming effects in this task, we conducted
      two experiments with an incremental priming paradigm using four stimulus-onset
      asynchronies (13, 27, 40, and 53 ms). Experiment 1 was conducted under a
      predictive-contingency scenario (probe-prime-target; i.e., "same" trials: HOUSE
      house-HOUSE vs. house-water-HOUSE; "different" trials: field-house-HOUSE vs.
      field-water-HOUSE), while Experiment 2 employed a zero-contingency scenario
      (i.e., "same" trials: HOUSE-house-HOUSE vs. house-water-HOUSE; "different"
      trials: field-field-HOUSE vs. field-water-HOUSE). Results revealed that, for
      "same" responses, both facilitation and inhibition increased linearly with prime
      duration in the two scenarios, whereas the pattern of data varied for "different"
      responses, as predicted by the Bayesian Reader model.

PMID- 21722061
TI  - "Can you spare an organ?": exploring Hispanic Americans' willingness to discuss
      living organ donation with loved ones.
AB  - Living organ donation offers a means of overcoming the shortage of viable organs
      available for transplant: a shortage particularly problematic among Hispanics.
      One barrier standing between those in need of a kidney and a successful
      transplant operation is an inability, and often lack of desire, to talk to loved
      ones about the need for a living donation. With an eye on future intervention
      approaches, and guided in part by the theory of planned behavior, this research
      effort sought to explore the factors associated with a willingness to engage in a
      conversation about a living donation with loved ones. Study 1, a phone survey of
      Hispanic Americans drawn from a Hispanic surname list, reveals that while upward
      of 90% of respondents would be willing to offer a kidney to a family member in
      need, and a similar percentage would be willing to accept a living donation if
      offered, only about half of respondents would feel comfortable initiating a
      conversation with family members if the respondent was in need of a living
      donation. Study 2, a survey of Hispanic American patients currently in need of a
      living kidney donation, revealed that perceived behavioral control accounted for
      60% of the variance in future intentions to initiate a conversation among those
      who have yet to speak to a family member about becoming a living donor. Moreover,
      perceived behavioral control mediated the relationship between perceived asking
      appropriateness and future intentions to initiate a conversation. Lastly,
      recipient outcome expectations, asking appropriateness, and subjective norms were
      revealed to be predictive of perceived behavioral control. Implications for
      future living donor interventions focusing on increasing recipient-initiated
      conversations are discussed.

PMID- 21722063
TI  - Homophonic context effects when naming Japanese kanji: evidence for processing
      costs?
AB  - The current study investigated the effects of phonologically related context
      pictures on the naming latencies of target words in Japanese and Chinese. Reading
      bare words in alphabetic languages has been shown to be rather immune to effects
      of context stimuli, even when these stimuli are presented in advance of the
      target word (e.g., Glaser & Dungelhoff, 1984 ; Roelofs, 2003 ). However,
      recently, semantic context effects of distractor pictures on the naming latencies
      of Japanese kanji (but not Chinese hanzi) words have been observed (Verdonschot,
      La Heij, & Schiller, 2010 ). In the present study, we further investigated this
      issue using phonologically related (i.e., homophonic) context pictures when
      naming target words in either Chinese or Japanese. We found that pronouncing bare
      nouns in Japanese is sensitive to phonologically related context pictures,
      whereas this is not the case in Chinese. The difference between these two
      languages is attributed to processing costs caused by multiple pronunciations for
      Japanese kanji.

PMID- 21722062
TI  - Neurocognitive and family functioning and quality of life among young adult
      survivors of childhood brain tumors.
AB  - Many childhood brain tumor survivors experience significant neurocognitive late
      effects across multiple domains that negatively affect quality of life. A
      theoretical model of survivorship suggests that family functioning and survivor
      neurocognitive functioning interact to affect survivor and family outcomes. This
      paper reviews the types of neurocognitive late effects experienced by survivors
      of pediatric brain tumors. Quantitative and qualitative data from three case
      reports of young adult survivors and their mothers are analyzed according to the
      theoretical model and presented in this paper to illustrate the importance of key
      factors presented in the model. The influence of age at brain tumor diagnosis,
      family functioning, and family adaptation to illness on survivor quality of life
      and family outcomes is highlighted. Future directions for research and clinical
      care for this vulnerable group of survivors are discussed.

PMID- 21722064
TI  - The role of working memory capacity in multiple-cue probability learning.
AB  - Multiple-cue probability learning (MCPL) involves learning to predict a criterion
      when outcome feedback is provided for multiple cues. A great deal of research
      suggests that working memory capacity (WMC) is involved in a wide range of tasks
      that draw on higher level cognitive processes. In three experiments, we examined
      the role of WMC in MCPL by introducing measures of working memory capacity, as
      well as other task manipulations. While individual differences in WMC positively
      predicted performance in some kinds of multiple-cue tasks, performance on other
      tasks was entirely unrelated to these differences. Performance on tasks that
      contained negative cues was correlated with working memory capacity, as well as
      measures of explicit knowledge obtained in the learning process. When the
      relevant cues predicted positively, however, WMC became irrelevant. The results
      are discussed in terms of controlled and automatic processes in learning and
      judgement.

PMID- 21722066
TI  - Dense fouling in acid transfer pipelines by an acidophilic rubber degrading
      fungus.
AB  - An unique case of dense fouling by an acidophilic, hard rubber (polymerized
      rubber) degrading fungus in the acid transfer pipelines of a boron enrichment
      plant located at Kalpakkam, India is reported. In spite of a highly adverse
      environment for survival (pH 1.5, no dissolved nutrients), the fungus thrived and
      clogged the pipeline used for transferring 0.1N hydrochloric acid (HCl). Detailed
      investigations were carried out to isolate and identify the fungus and examine
      the nutrient source for such profuse growth inside the system. Microscopic
      observation showed the presence of a thick filamentous fungal biomass. Molecular
      characterization by 18S rRNA gene sequencing showed 98% similarity of the isolate
      with the acidophilic fungus Bispora sp. In laboratory studies the fungus showed
      luxuriant growth (specific growth rate of 13 mg day-1) when scrapings of the hard
      rubber were used as the sole source of carbon. Scanning electron microscopy
      revealed extensive incursion of the fungus into the hard rubber matrix. In the
      laboratory, fungal growth was completely inhibited by the antifungal agent sodium
      omadine. The study illustrates an interesting example of biofouling under extreme
      conditions and demonstrates that organisms can physiologically adapt to grow
      under unfavourable conditions, provided that a nutrient source is available and
      competition is low. The use of this fungal strain in biodegradation and in
      development of environmentally compatible processes for disposal of rubber wastes
      is envisaged.

PMID- 21722067
TI  - Exercise and quality of life in patients with cystic fibrosis: A 12-week
      intervention study.
AB  - It was hypothesised that increased exercise capacity is related to improved
      quality of life (QoL) in patients with cystic fibrosis (CF). A 12-week
      individually tailored unsupervised aerobic exercise programme was offered to 42
      patients with CF. At the start and at the end of the exercise programme, data on
      QoL, current exercise habits and preferences, anthropometric data, exercise test,
      and lung function test were collected. Adherence was observed by a heart rate
      (HR) monitor. A total of 24 patients accepted to be enrolled in the exercise
      programme and 14 completed the programme. Another 14 patients declined to be
      enrolled in the exercise programme but completed the Cystic Fibrosis
      Questionnaire for Adolescents and Adults (CFQ-R 14+). Four patients did not want
      to participate at all. The 14 patients completing the exercise programme had a
      significantly increased VO(2max), but they showed no significant change in total
      QoL score. However, the scores in the domain of treatment burden and emotional
      functioning increased significantly. There was no significant difference in QoL
      and lung function between patients participating in the exercise programme (n =
      24) and non-participants (n = 14). A 12-week individually tailored unsupervised
      aerobic exercise programme where HR monitors were used significantly affected
      VO(2max). Improvement in QoL could not be demonstrated in this study.

PMID- 21722068
TI  - Dietary self-monitoring and its impact on weight loss in overweight children.
AB  - OBJECTIVE: To examine whether dietary self-monitoring is related to weight loss
      in overweight children and whether perceived social support or dietary self
      efficacy affects this relation. Design. Longitudinal, behavioral intervention
      study. SUBJECTS: The study population included 153 children, aged 7-12 years,
      with daily food records from a 20-week weight loss program in San Diego,
      California, USA, conducted between 1999 and 2002. Methods. Self-monitoring was
      assessed using two methods: a weekly index as a measure of competency (possible
      range -7 to +35) and recording sufficiency for total compliance (percentage of
      days). RESULTS: Significantly greater decreases in percentage overweight were
      found for children with recording competency at or above the median (mean change:
      -13.4% vs. -8.6%; p < 0.001) or who were compliant in recording -50% of the days
      (mean change: -13.0% vs. ?8.4%; p < 0.001). Using hierarchical linear regression,
      children who had a higher average weekly monitoring index or recorded
      sufficiently on more days had significantly greater decreases in percent
      overweight, after adjusting for age, sex, SES, race/ethnicity and baseline
      percent overweight (p < 0.001). Perceived social support at baseline and dietary
      self-efficacy were not related to self-monitoring or change in percent overweight
      in this sample. CONCLUSION: As has been demonstrated with adults and adolescents,
      self-monitoring in children was associated with greater decreases in percent
      overweight. However, dietary self-efficacy and perceived social support were not
      related to how frequently or thoroughly they monitored dietary intake.

PMID- 21722069
TI  - IFN-gamma and TNF-alpha induce a different modulation of interleukin-6 in
      systemic sclerosis fibroblasts compared to healthy controls.
AB  - BACKGROUND: To our knowledge, no previous study has evaluated the effect of
      interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, or their combination
      on the prototype proinflammatory cytokine interleukin (IL)-6 in primary cultured
      fibroblasts from patients with systemic sclerosis (SSc) at an early stage of the
      disease. METHODS: Fibroblast cultures from five SSc patients (disease duration <
      2 years) and five healthy controls were evaluated for the basal production of IL
      6, and after stimulation with TNF-alpha or IFN-gamma, alone or combined. RESULTS:
      The fibroblasts from SSc patients produced higher levels of IL-6 in basal
      condition than controls [617 +/- 173 vs. 213 +/- 123 pg/mL; analysis of variance
      (ANOVA), p < 0.001]. TNF-alpha was able to dose-dependently induce IL-6 in SSc
      (609 +/- 184, 723 +/- 243, 1079 +/- 297, 1436 +/- 326 pg/mL, with TNF-alpha 0, 1,
      5, 10 ng/mL, respectively) but not in control fibroblasts, whereas IFN-gamma was
      unable to induce IL-6. Furthermore, the combination of IFN-gamma and TNF-alpha
      induced a stronger secretion of IL-6 in SSc fibroblasts (ANOVA, p < 0.0001),
      without effect in controls. CONCLUSIONS: SSc fibroblasts participate in the self
      perpetuation of inflammation by releasing IL-6, under the influence of TNF-alpha
      and/or IFN-gamma.

PMID- 21722070
TI  - Clinical features of axial undifferentiated spondyloarthritis (USpA) in China:
      HLA-B27 is more useful for classification than MRI of the sacroiliac joint.
AB  - OBJECTIVES: To analyse the clinical features of Chinese undifferentiated
      spondyloarthritis (USpA) patients with predominantly axial involvement, and in
      particular the influence of human leucocyte antigen (HLA)-B27 and magnetic
      resonance imaging (MRI) of the sacroiliac joint (SIJ) on the classification of
      axial USpA. METHODS: Patients with low back pain for >= 3 months and no definite
      radiographic sacroiliitis were enrolled in this study. They were diagnosed as
      USpA based on rheumatologists' findings. Correlations between clinical features
      and HLA-B27 status or MRI manifestations were analysed. RESULTS: A total of 197
      USpA patients were recruited, of whom 135 (70.3%) were positive for HLA-B27.
      Acute inflammation, structural damage lesions, and normal findings on SIJ MRI
      were recorded in 64.5, 13.2 and 22.3% of patients, respectively. Classification
      criteria for axial SpA according to the European Spondylarthropathy Study Group
      (ESSG), Amor, and the Assessment of SpondyloArthritis International Society
      (ASAS) were fulfilled by 63.5, 64.5 and 83.2% patients, respectively. Cross
      validation showed significant correlation among these three criteria. Patients
      positive for HLA-B27 included more males, with earlier onset age, better response
      to non-steroidal anti-inflammatory drugs (NSAIDs), and higher erythrocyte
      sedimentation rate (ESR)/C-reactive protein (CRP) levels. In addition, more HLA
      B27-positive than HLA-B27-negative patients fulfilled the ESSG, Amor, and ASAS
      criteria. Patients with acute inflammation on SIJ MRI had a higher level of
      ESR/CRP, and a greater proportion of them fulfilled the Amor and ASAS criteria.
      However, the proportion of those fulfilling the ESSG criteria did not differ with
      different MRI manifestations. CONCLUSION: Both HLA-B27 status and SIJ MRI
      findings influence the classification of Chinese axial USpA patients, but HLA-B27
      seems of more value.

PMID- 21722071
TI  - Faecal incontinence in patients with systemic sclerosis: is an impaired internal
      anal sphincter the only cause?
AB  - OBJECTIVES: Faecal incontinence affects 40% of patients with systemic sclerosis
      (SSc). Several factors, including impaired anal sphincter function, reduced
      rectoanal sensation, abnormal rectoanal wall properties, and fast
      gastrointestinal transit, can cause faecal incontinence. Internal anal sphincter
      function is reduced in some patients with SSc, but other factors causing faecal
      incontinence remain to be studied in detail. Our aim was to compare tests of
      colorectal and anal physiology in patients with SSc suffering from faecal
      incontinence to those of SSc patients without faecal incontinence and healthy
      controls. METHODS: Twenty SSc patients [18 women, mean age 58 (range 38-79)
      years] with bowel dysfunction were examined using rectoanal physiology tests,
      impedance planimetry, radiographic assessment of gastrointestinal transit time,
      and the Wexner incontinence score questionnaire. The results from SSc patients
      with faecal incontinence (n = 8) were compared to those from patients without
      faecal incontinence (n = 12) and healthy subjects [rectoanal physiology tests: 24
      women, mean age 72 (range 65-83) years; impedance planimetry: 20 women, mean age
      51 (range 40-80) years]. RESULTS: Anal resting pressure, which reflects internal
      anal sphincter function, was significantly reduced in SSc patients with faecal
      incontinence but not in those without. There were no significant differences in
      external anal sphincter function, rectoanal sensibility, rectal wall properties,
      or gastrointestinal transit time. CONCLUSION: The main cause of faecal
      incontinence in SSc is poor function of the internal anal sphincter smooth
      muscle.

PMID- 21722072
TI  - Association between myasthaenia gravis and systemic lupus erythematosus: three
      case reports and review of the literature.
AB  - The coexistence of systemic lupus erythematosus (SLE) and myasthaenia gravis (MG)
      has been reported previously. Because of their shared clinical characteristics
      and autoantibody-mediated pathogenesis, an SLE expert panel decided to include MG
      as one of the 19 neuropsychiatric SLE syndromes.   This study reports a cluster
      of three cases of SLE/MG overlap from our cohort and a review of the published
      data concerning this overlap of SLE and MG. A systematic Medline review revealed
      13 cases described in eight publications from 1994 to 2009. In summary, 12 of the
      16 patients (three from our cohort and 13 from the reported cases) were women
      with an average age of 34 years. The most common SLE manifestations were
      polyarthritis (15 out of 16 patients), skin rashes (5/16), serositis (5/16), and
      cytopaenias (10/16). All of the patients were anti-nuclear antibodies (ANA)
      positive and 15/16 were anti-dsDNA positive. Proximal muscle weakness was the
      most frequent MG-related symptom (9/16), while 11/16 patients were anti
      acetylcholine receptor (anti-AChR) antibody positive and 9/16 had diagnostic
      electromyography (EMG).   These data suggest that MG should to be included in the
      differential diagnosis of lupus patients with fatigue and muscular weakness
      together with inflammatory and drug-induced myopathy.

PMID- 21722073
TI  - Soluble urokinase plasminogen activator receptor (suPAR) levels in healthy
      pregnancy and preeclampsia.
AB  - BACKGROUND: Preeclampsia is characterized by a maternal systemic inflammatory
      response and the impairment of maternal immune tolerance present in healthy
      pregnancy. Soluble urokinase plasminogen activator receptor (suPAR) is a
      biomarker increasingly used for the monitoring of systemic inflammation. We aimed
      to assess the levels of suPAR and other markers of systemic inflammation in
      preeclampsia compared to healthy pregnancy. METHODS: We determined plasma suPAR,
      IL-6 and high sensitivity C-reactive protein (hs-CRP) levels in plasma samples of
      62 healthy pregnant and 41 preeclamptic women in the third trimester of
      pregnancy. RESULTS: Plasma suPAR levels were elevated in preeclampsia [3.18 (2.30
      4.71) ng/mL vs. 2.02 (1.81-2.40) ng/mL, p=0.0001, median (interquartile range)].
      IL-6 and hs-CRP levels were also higher compared with healthy pregnancy [5.99
      (2.97-18.12) pg/mL vs. 1.41 (1.00-2.70) pg/mL, p=0.0001 and 6.60 (3.55-15.40)
      mg/L vs. 3.90 (2.10-7.25) mg/L, p=0.006, respectively, median (interquartile
      range)]. Linear regression analyses revealed an association between individual
      plasma suPAR and log IL-6 levels as well as log hs-CRP levels. CONCLUSIONS: suPAR
      levels are elevated in preeclampsia and vary in a narrower range compared with IL
      6 and hs-CRP. ROC analysis indicated that monitoring of suPAR levels is a
      suitable tool for the detection of systemic inflammation in pregnancy.

PMID- 21722074
TI  - Association of a functional polymorphism in the MMP7 gene promoter with
      susceptibility to vulnerable carotid plaque in a Han Chinese population.
AB  - BACKGROUND: Matrix metalloproteinase-7 (MMP-7) may play an important role in the
      development of vulnerable carotid plaque. An A-to-G transition (-181A/G) in the
      promoter region of MMP7 is functional in vitro by altering the transcriptional
      activity of the gene. The aim of this study was to investigate the association
      between the MMP7 -181A/G polymorphism and vulnerable carotid plaque formation.
      METHODS: The authors enrolled 641 patients and divided them into three groups
      according to the carotid ultrasound examination: vulnerable plaque group (n=118),
      stable plaque group (n=385) and no plaque group (n=138). Traditional
      atherosclerosis risk factors were recorded and the MMP7 -181A/G polymorphism was
      genotyped by polymerase chain reaction-restriction fragment length polymorphism.
      RESULTS: In the multinomial logistic regression analysis, compared to the no
      plaque group, no relationship between MMP7 -181AG+GG genotypes and stable carotid
      plaque was observed [odds ratio (OR) 1.50; p=0.239]. However, the frequency of
      AG+GG genotypes was significantly higher in the vulnerable plaque group (OR 2.74;
      p=0.008). Age was a risk factor for plaque formation, while statin treatment can
      reduce the prevalence of atherosclerotic plaque. Additionally, using binary
      logistic regression analysis between the stable and vulnerable plaque groups,
      this MMP7 polymorphism was associated with vulnerable plaque independently of
      other factors [OR 1.83; 95% confidence interval 1.08- 3.11; p=0.026].
      CONCLUSIONS: The MMP7 -181A/G polymorphism is associated with the development of
      vulnerable carotid plaques. Age is a risk factor for plaque formation, while
      statin therapy is associated with a decreased prevalence of carotid atheromatous
      plaques.

PMID- 21722076
TI  - Providing families with relevant information: how can we improve our service
      system?

PMID- 21722078
TI  - Measurement of plasma amino acids by Ultraperformance(r) Liquid Chromatography.
AB  - BACKGROUND: Since the early 1960s, quantitative amino acid analysis (AAA) has
      traditionally been performed using ion-exchange chromatography with post-column
      ninhydrin derivatization. This established technology has many advantages,
      including relatively low cost of operation and ease of use. However, analysis
      times of 120+ min and high maintenance requirements make this technology
      unsuitable for the modern clinical laboratories with a requirement for rapid
      turnaround times. The work described here is a summary of our experiences with a
      new approach to full profile analysis of physiological amino acids. METHODS:
      Amino acids were derivatized in batches with a proprietary reagent, AccQTag(r),
      which reacts with primary and secondary amines. The derivatized amino acids were
      separated using Ultraperformance(r) Liquid Chromatography (UPLC). In a
      prospective method comparison, quantitative plasma amino acid data obtained from
      approximately 170 patient samples using both the UPLC method and a traditional
      ion-exchange chromatography amino acid analyzer were evaluated. RESULTS: The data
      obtained from the two methods were found to agree well. Correlation coefficients
      for the most important amino acids seen in inborn errors of metabolism, such as
      phenylalanine, tyrosine and branched chain amino acids varied from 0.8658 to
      0.9932 with minor slope biases. This approach also reduced the run time from 120
      to 45 min per sample using a sample volume of 0.1 mL, compared to the 0.5 mL
      volume required for ion-exchange chromatography. CONCLUSIONS: This new approach
      for the full profile analysis of physiological amino acids has been shown to be a
      viable substitute for current ion-exchange methodologies. It provides substantial
      benefits including significant reductions in runtime and necessary sample volume
      for the investigation and monitoring of patients with metabolic disorders and for
      nutritional management of a variety of patients.

PMID- 21722077
TI  - Gender differences affecting vocal health of women in vocally demanding careers.
AB  - Studies suggest that occupational voice users have a greater incidence of vocal
      issues than the general population. Women have been found to experience vocal
      health problems more frequently than men, regardless of their occupation.
      Traditionally, it has been assumed that differences in the laryngeal system are
      the cause of this disproportion. Nevertheless, it is valuable to identify other
      potential gender distinctions which may make women more vulnerable to voice
      disorders. A search of the literature was conducted for gender-specific
      characteristics which might impact the vocal health of women. This search can be
      used by health care practitioners to help female patients avoid serious vocal
      health injuries, as well as to treat better those women who already suffer from
      such vocal health issues.

PMID- 21722079
TI  - Letter to the editor reply: Statistical methods for assessment of added
      usefulness of new biomarkers.

PMID- 21722080
TI  - Investigation on gene transfer from genetically modified corn (Zea mays L.)
      plants to soil bacteria.
AB  - Knowledge about the prevalence and diversity of antibiotic resistance genes in
      soil bacteria communities is required to evaluate the possibility and ecological
      consequences of the transfer of these genes carried by genetically modified (GM)
      plants to soil bacteria. The neomycin phosphotransferase gene (nptII) conferring
      resistance to kanamycin and neomycin is one of the antibiotic resistance genes
      commonly present in GM plants. In this study, we investigated kanamycin-resistant
      (Km(R)) and neomycin-resistant (Nm(R)) soil bacterial populations in a 3-year
      field trial using a commercial GM corn (Zea mays L.) carrying the nptII gene and
      its near isogenic line. The results showed that a portion (2.3 - 15.6 %) of
      cultivable soil bacteria was naturally resistant to kanamycin or neomycin.
      However, no significant difference in the population level of Km(R) or Nm(R) soil
      bacteria was observed between the GM and non-GM corn fields. The nptII gene was
      not detected in any of the total 3000 Km(R) or Nm(R) isolates screened by PCR.
      Further, total soil bacterial cells were collected through Nycodenz gradient
      centrifugation and bacterial community DNA was subjected to PCR. Detection limit
      was about 500 cells per gram of fresh soil. Our study suggests that the nptII
      gene was relatively rare in the soil bacterial populations and there was no
      evidence of gene transfer from a GM corn plant to soil bacteria based on the data
      from total soil bacterial communities.

PMID- 21722081
TI  - Validation of the criteria for initiating the cleaning of heating, ventilation,
      and air-conditioning (HVAC) ductwork under real conditions.
AB  - Dust accumulation in the components of heating, ventilation, and air-conditioning
      (HVAC) systems is a potential source of contaminants. To date, very little
      information is available on recognized methods for assessing dust buildup in
      these systems. The few existing methods are either objective in nature, involving
      numerical values, or subjective in nature, based on experts' judgments. An
      earlier project aimed at assessing different methods of sampling dust in ducts
      was carried out in the laboratories of the Institut de recherche Robert-Sauve en
      sante et en securite du travail (IRSST). This laboratory study showed that all
      the sampling methods were practicable, provided that a specific surface-dust
      cleaning initiation criterion was used for each method. However, these
      conclusions were reached on the basis of ideal conditions in a laboratory using a
      reference dust. The objective of this present study was to validate these
      laboratory results in the field. To this end, the laboratory sampling templates
      were replicated in real ducts and the three sampling methods (the IRSST method,
      the method of the U.S. organization National Air Duct Cleaner Association [NADCA]
      and that of the French organization Association pour la Prevention et l'Etude de
      la Contamination [ASPEC]) were used simultaneously in a statistically
      representative number of systems. The air return and supply ducts were also
      compared. Cleaning initiation criteria under real conditions were found to be 6.0
      mg/100 cm(2) using the IRSST method, 2.0 mg/100 cm(2) using the NADCA method, and
      23 mg/100 cm(2) using the ASPEC method. In the laboratory study, the criteria
      using the same methods were 6.0 for the IRSST method, 2.0 for the NADCA method,
      and 3.0 for the ASPEC method. The laboratory criteria for the IRSST and NADCA
      methods were therefore validated in the field. The ASPEC criterion was the only
      one to change. The ASPEC method therefore allows for the most accurate evaluation
      of dust accumulation in HVAC ductwork. We therefore recommend using the latter
      method to objectively assess dust accumulation levels in HVAC ductwork.

PMID- 21722082
TI  - Number concentration and size distribution of ultrafine particles on the roadside
      of the Tateyama-Kurobe Alpine route, Japan.
AB  - Measurements of ultrafine particles (UFPs) with diameters smaller than 100 nm
      were made with a Scanning Mobility Particle Sizer on the roadside of the Tateyama
      Kurobe Alpine route on the western slope of Mt. Tateyama, Japan, in the summer
      and autumn of 2007 and 2008. The number concentrations of nanoparticles (NPs)
      with diameters smaller than 50 nm increased sharply in the morning. This increase
      agreed with that of the NO concentration, which is a good indicator of vehicle
      emissions. Although the peak concentration of NO was also detected in the late
      afternoon, the concentrations of NPs did not increase. The vehicle emission of
      UFPs may vary considerably with the driving conditions. The emission of NPs might
      have been accelerated under a high engine-load condition. The NP concentrations
      in October were much higher than those in August, although there were more buses
      in August than in October. The number size distribution in the morning was
      bimodal, with the first peak around 20-30 nm and the second one around 70-80 nm.
      The first peak became small during the daytime. The first peak disappeared, and a
      small second peak remained through midnight.

PMID- 21722083
TI  - Review of advances in the thin layer chromatography of pesticides: 2008-2010.
AB  - Techniques and applications of thin layer chromatography (planar chromatography)
      for the separation, detection, qualitative and quantitative determination, and
      preparative isolation of pesticides and their metabolites and other related
      compounds are reviewed for the period from November 1, 2008 to November 1, 2010.
      Analyses are described for a variety of samples types and pesticide classes. In
      addition to references on residue analysis, studies such as pesticide structure
      retention relationships, identification and characterization of plant pesticides
      and synthesized pesticides, metabolism, degradation, mobility, identification of
      biomarkers for detection of herbicide effects in plants, and lipophilicity are
      covered.

PMID- 21722084
TI  - Adsorption and desorption processes of MCPA in Polish mineral soils.
AB  - Studies on the adsorption and desorption of MCPA (4-chloro-2-methylophenoxyacetic
      acid) were performed in soil horizons of three representative Polish agricultural
      soils. The Hyperdystric Arenosol, the Haplic Luvisol and the Hypereutric Cambisol
      were investigated in laboratory batch experiments. Initially, both the adsorption
      and desorption proceeded rapidly, and either the equilibrium was reached after
      approximately 30 min or the process slowed down and continued at a slow rate. In
      the latter case, the equilibrium was reached after 8 hours. Data on the
      adsorption/desorption kinetics fitted well to the two-site kinetic model. The
      measured sorption and desorption isotherms were of L-type. The sorption
      distribution coefficients (K(ads) (d)) were in the range of 0.75--0.97 for Ap
      soil horizons and significantly lower in deeper soil layers. The corresponding
      desorption coefficients (K(des) (d)) were higher and ranged from 1.02 to 2.01.
      Both the adsorption and desorption of MCPA in all soil horizons was strongly and
      negatively related to soil pH. It appears that hydrophobic sorption plays a
      dominant role in the MCPA retention in topsoils whereas hydrophilic sorption of
      MCPA anions is the dominant adsorption mechanism in subsoils.

PMID- 21722085
TI  - Application of advanced oxidation processes to doxycycline and norfloxacin
      removal from water.
AB  - Doxycycline (Dxy) and Norfloxacin (Nfx) have been oxidized by means of different
      technologies of increasing complexity. Preliminary experiments showed that
      activated carbon adsorption (1.0 g L-1) of these antibiotics (C(Antibiotic) = 5 *
      10-5 M) led to a 60 and 85 % of total organic carbon (TOC) removal, however, a
      significant decrease in adsorption capacity was experienced after several reuses
      of the adsorbent. UV-C irradiation of Dxy (20 % removal in 2 h) or Nfx (90 %
      removal in 2 h) did not affect the initial TOC content of the solution while
      single ozonation (C(O3) gas inlet concentration = 15.0 ppm) led to the
      instantaneous disappearance of the parent compounds while TOC conversion values
      in the proximity of 40 % were obtained. Complex systems based on the combination
      of ozone, UV-C radiation, titanium dioxide and activated carbon led to similar
      TOC removals of the order of 70 and 65 % for Dxy and Nfx, respectively. An
      attempt has been made to calculate the quantum yield and direct ozonation rate
      constants for doxycycline and norfloxacin. Additionally, the best systems, i.e.,
      the O3 and O3/UV-C processes, have been simulated by a pseudoempirical model by
      considering TOC as a surrogate parameter.

PMID- 21722086
TI  - Effects of xenoestrogens on the expression of vitellogenin (vtg) and cytochrome
      P450 aromatase (cyp19a and b) genes in zebrafish (Danio rerio) larvae.
AB  - In the present study, expression levels of vitellogenin (vtg) and cytochrome P450
      aromatase genes (cyp19a and cyp19b) in zebrafish larvae during the early stages
      of development were investigated by quantitative real time-PCR assay. The results
      indicated that vtg gene transcription was induced seven days after zebrafish
      larvae fertilization, whereas the expression of cyp19a and cyp19b genes was
      detected as early as 3 and 4 days post-fertilization (dpf). Investigations into
      the effects of 17beta-estradiol (E2) exposure on the expression of these genes
      showed that both vtg and cyp19b were upregulated by E2 in zebrafish larvae as
      early as four dpf, whereas no variation was observed in cyp19a gene expression.
      The estrogenic potential of pharmaceutical estrogen (DES), phenol estrogen (BPA)
      and the brominated flame retardants, TBBPA, DE-71 and 4-BP, were evaluated by
      analyzing the expression of these three genes in zebrafish larvae. The results
      demonstrated that natural estrogen, endocrine disrupting compounds and brominated
      flame retardants act as endocrine disrupters through different mechanisms. We
      have demonstrated for the first time that the polybrominated diphenyl ether
      mixture, DE-71, acts as an endocrine disrupter by upregulation of cyp19b gene
      expression at a relatively low concentration. These results indicate that
      analysis of vtg and cyp19b gene expression in zebrafish during early
      embryogenesis and organogenesis represents the basis of a sensitive and fast
      bioassay for the routine assessment of xenoestrogen effects.

PMID- 21722087
TI  - Higher throughput human hepatocyte assays for the evaluation of time-dependent
      inhibition of CYP3A4.
AB  - Time-dependent or mechanism-based CYP3A4 inhibition is an important adverse drug
      property that should be carefully managed during drug development. Evaluation of
      time-dependent inhibition is traditionally performed using liver microsomes or
      recombinant P450 isoforms. We report here higher throughput approaches to
      evaluate time-dependent CYP3A4 inhibition assay using cultured cryopreserved
      human hepatocytes. The assays were performed in human hepatocytes cultured in 96
      well plates, with luciferin-IPA as the CYP3A4 specific substrate. The advantages
      of the approach are as follows: 1. The use of 96-well plates minimizes the
      quantity of human hepatocytes and test materials required for the assays. 2. The
      use of luciferin-IPA allows CYP3A4 activity to be quantified rapidly using a
      plate reader, thereby avoiding the need for LC/MS that is required for
      traditional substrates such as testosterone and midazolam. 3. The use of cultured
      (plated) hepatocytes allows effective removal of treatment medium and washing of
      the cells without the laborious centrifugation step that is required for
      hepatocytes in suspension. Two assays were developed: 1. IC(50) shift assay; and
      2. enzyme kinetic assay. The IC-50 shift assay is intended for general screening
      purpose with which a time-dependent CYP3A4 inhibitor would be identified by an
      increase in inhibitory potency (quantified as a decrease in IC(50)) upon a 30
      min. pre-incubation of hepatocytes with the inhibitor at 37 deg. C. Results with
      model inhibitors showed that the IC50 assay readily distinguished the time
      dependent inhibitors (1-aminobenzotriazole, erythromycin) from the non-time
      dependent inhibitor (ketoconazole). The enzyme kinetic assay is used for the
      derivation of the kinetic parameters K(I) and k(inact). With this assay, time and
      concentration dependent inhibition of CYP3A4 were observed for 1
      aminobenzotriazole and erythromycin. With hepatocytes from 4 donors, K(I) and
      k(inact) values were calculated to be 22.0 to 70.7 uM, and 0.09 to 0.51 min(-1),
      respectively, for 1-aminobenzotriazole; and 47.3 to 75.1 uM, and 0.26 to 1.48,
      respectively, for erythromycin. DMSO (tested up to 2% v/v) was found to
      significantly attenuate the time-dependent inhibitory effects of 1
      aminobenzotriazole, and had no apparent effects on erythromycin. Acetonitrile and
      methanol at 1% v/v had no significant effects. The higher throughput assays
      describe here can to be used routinely for the evaluation of time-dependent
      CYP3A4 inhibitory potential of drug candidates during early phases of drug
      development.

PMID- 21722088
TI  - Impact of impurities on IC50 values of P450 inhibitors.
AB  - During early drug discovery, the synthetic pathways for test compounds are not
      well defined and impurities in the test compounds are inevitable. Compounds
      undergo serial screening tests at this stage to assess their biological
      activities and drug-like properties. Impurities in the test compounds can produce
      false positive results and therefore complicate the interpretation of data. P450
      inhibition is one of the screens used in the early drug discovery process to
      assess the potential of drug-drug interactions caused by the inhibition of P450
      enzymes. The impact of impurities on P450 inhibition has not been investigated.
      In this study, the impact of impurities on CYP2D6 IC(50) values was evaluated
      using model compounds. Cimetidine was chosen as the test compound. Quinidine,
      fluoxetine, fluvoxamine, and ibuprofen were chosen to represent impurities as
      they inhibit CYP2D6 to varying degrees. The IC(50) values of these model
      impurities for CYP2D6 were 0.11 uM, 0.98 uM, 13.4 uM, and >100 uM, respectively.
      Impurities with potent CYP2D6 inhibition, such as quinidine, can significantly
      decrease the apparent IC(50) value for the mixture. With the addition of only 2%
      quinidine to cimetidine (mol/mol), the apparent IC(50) value of cimetidine
      decreased from 98 uM to 4.4 uM. With the addition of 10% quinidine, the apparent
      IC(50) decreased to 1.04 uM. Such a significant decrease in apparent IC(50)
      values can produce a false alert and cause the inappropriate elimination of good
      compounds at an early stage. Impur6ities with low inhibitory potential, such as
      fluvoxamine and ibuprofen, did not cause a significant change in apparent IC(50)
      values. An impurity can have a similar effect on the IC(50) values for inhibition
      of other biological activities. The effect of an impurity on apparent IC(50)
      values can be predicted by using a simulation curve if the potency of the
      impurity is characterized.

PMID- 21722089
TI  - Formation and anti-tumor activity of uncommon in vitro and in vivo metabolites of
      CPI-613, a novel anti-tumor compound that selectively alters tumor energy
      metabolism.
AB  - CPI-613 is a novel anti-tumor compound with a mechanism-of-action which appears
      distinct from the current classes of anti-cancer agents used in the clinic. CPI
      613 demonstrates both in vitro and in vivo anti-tumor activity. In vitro
      metabolic studies using liver S9 were performed which demonstrated that CPI-613
      undergoes both phase 1 (oxidation) and phase 2 (glucuronidation) transformations.
      Its metabolic half-life varied between species and ranged from 8 minutes (Hanford
      minipig) to 47 minutes (CD-1 mouse). We performed metabolite mass assessments
      using selected in vitro incubation samples and demonstrated that +16 amu
      oxidation with and without +176 amu glucuronidation products were generated by
      human and animal liver S9. LC/MS/MS fragmentation patterns showed that an
      uncommon sulfoxide metabolite was formed and the O-glucuronidation occurred at
      the terminal carboxyl moiety. We observed that the +192 amu sulfoxide/glucuronide
      was generated only in human liver S9 and not by any of the other species tested.
      Synthetic metabolites were prepared and compared with the enzymatically-generated
      metabolites. Both the chromatographic retention times and the LC/MS/MS
      fragmentation patterns were similar, demonstrating that the synthetic metabolites
      were virtually identical to the S9-generated products. CYP450 reaction
      phenotyping and inhibition data both suggested that multiple CYP isozymes (2C8
      and 3A4, along with minor contributions by 2C9 and 2C19) were involved in CPI-613
      metabolism and sulfoxide formation. Plasma samples from human subjects dosed with
      CPI-613 also contained the sulfoxide +/- glucuronide metabolites. These results
      show that the in vitro- and in vivo-generated phase 1 and phase 2 metabolites
      were in good agreement.

PMID- 21722090
TI  - Tracing fungi secondary metabolites in Brazil nuts using LC-MS/MS.
AB  - This screening aimed to evaluate quantitatively the occurrence of fungal
      metabolites in Brazil nuts. Nuts were collected from Agroforest production areas
      in Amazon basin region. A total of 235 mycotoxins (including the most prominent
      ones) was screened by a multi-mycotoxin method based on HPLC-MS/MS. The recovery
      of metabolites by the method was between 56 and 136%. Fifteen mycotoxins were
      detected and quantified, in at least one sample; namely, aflatoxins (AFB(1),
      AFB(2), AFG(1), and AFM(1)), sterigmatocystin, methyl-sterigmatocystin, kojic
      acid, citrinin, cyclosporin A, cyclosporin C, cyclosporin D, cyclosporin H,
      rugulosin, alternariol-methylether and emodin. This is the first study dealing
      with the detection of the latter nine metabolites in Brazil nuts. Alternariol
      methylether (from 0.75 to 3.2 ug/kg) was the only metabolite detected in all
      analyzed samples.

PMID- 21722092
TI  - Ameliorative effects of GW1929, a nonthiazolidinedione PPARgamma agonist, on
      inflammation and apoptosis in focal cerebral ischemic-reperfusion injury.
AB  - PPARgamma agonist; 2-(Benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L
      tyrosine (GW1929) in focal cerebral ischemic-reperfusion (IR) injury in rats.
      Focal cerebral IR injury resulted significant brain infarction and neurological
      deficits in rats. A significant increase in various inflammatory mediators like
      COX-2, iNOS, MMP-9, TNFalpha and IL-6 and massive apoptotic DNA fragmentation was
      also observed in the IR challenged brains. GW1929 treatment significantly
      attenuated the neurological damage in focal cerebral IR injury. Neuroprotective
      effects of GW1929 were found to be associated with significant reduction in the
      COX-2, iNOS, MMP-9, TNFalpha and IL-6 levels. Together, we have also evaluated
      the effects of Pioglitazone, a clinically available thiazolidinedione PPARgamma
      agonist, against focal cerebral IR injury. Like GW1929, Pioglitazone also showed
      beneficial effects in cerebral IR injury associated neurological damage but at
      the higher dose as compared to GW1929. Neuroprotective effects of PPARgamma
      agonists were found to be associated with significant reduction in TUNEL positive
      cells in IR challenged brain. In summary, these results suggested the
      neuroprotective potential of PPARgamma agonists in cerebral IR injury and these
      effects may be attributed to their anti-inflammatory and anti-apoptotic
      potential.

PMID- 21722091
TI  - Erythropoietin employs cell longevity pathways of SIRT1 to foster endothelial
      vascular integrity during oxidant stress.
AB  - Given the cytoprotective ability of erythropoietin (EPO) in cerebral
      microvascular endothelial cells (ECs) and the invaluable role of ECs in the
      central nervous system, it is imperative to elucidate the cellular pathways for
      EPO to protect ECs against brain injury. Here we illustrate that EPO relies upon
      the modulation of SIRT1 (silent mating type information regulator 2 homolog 1) in
      cerebral microvascular ECs to foster cytoprotection during oxygen-glucose
      deprivation (OGD). SIRT1 activation which results in the inhibition of apoptotic
      early membrane phosphatidylserine (PS) externalization and subsequent DNA
      degradation during OGD becomes a necessary component for EPO protection in ECs,
      since inhibition of SIRT1 activity or diminishing its expression by gene
      silencing abrogates cell survival supported by EPO during OGD. Furthermore, EPO
      promotes the subcellular trafficking of SIRT1 to the nucleus which is necessary
      for EPO to foster vascular protection. EPO through SIRT1 averts apoptosis through
      activation of protein kinase B (Akt1) and the phosphorylation and cytoplasmic
      retention of the forkhead transcription factor FoxO3a. SIRT1 through EPO
      activation also utilizes mitochondrial pathways to prevent mitochondrial
      depolarization, cytochrome c release, and Bad, caspase 1, and caspase 3
      activation. Our work identifies novel pathways for EPO in the vascular system
      that can govern the activity of SIRT1 to prevent apoptotic injury through Akt1,
      FoxO3a phosphorylation and trafficking, mitochondrial membrane permeability, Bad
      activation, and caspase 1 and 3 activities in ECs during oxidant stress.

PMID- 21722093
TI  - Dopamine and vascular dynamics control: present status and future perspectives.
AB  - The catecholamine dopamine is a precursors in the biosynthesis of norepinephrine
      and epinephrine as well as a neurotransmitter in the central nervous system.
      Besides of its well known role of brain neurotransmitter, dopamine exerts
      specific functions at the periphery, being those at the level of the
      cardiovascular system and the kidney the most relevant. In fact it plays a role
      of modulator of blood pressure, sodium balance, and renal and adrenal functions
      through an independent peripheral dopaminergic system. In vivo administration or
      in vitro application of dopamine or of dopamine receptor agonists induce
      vasodilatation in the cerebral, coronary, renal and mesenteric vascular beds and
      cause hypotension. Moreover, dopamine stimulates cardiac contractility and
      induces diuresis and natriuresis. Dopamine probably plays a role in the
      pathogenesis of arterial hypertension by regulating epithelial sodium transport,
      vascular smooth muscle contractility and production of reactive oxygen species
      and by interacting with the renin-angiotensin and sympathetic nervous systems.
      Dopamine exerts its actions via a class of cell surface receptors belonging to
      the rhodopsin-like family of G-protein coupled receptors. Dopamine receptors are
      classified into D1-like (D1 and D5) and D2-like (D2, D3 and D4) subtypes based on
      their structure and pharmacology. Each of the dopamine receptor subtypes can
      participate in the regulation of blood pressure by specific mechanisms. Some
      receptors regulate blood pressure by influencing the central and/or autonomic
      nervous system; others influence epithelial transport and regulate the secretion
      and receptors of several humeral agents. This paper outlines the biochemistry,
      anatomical localization and physiology of the different dopamine receptors
      involved in the regulation of blood pressure, the relationship between dopamine
      receptor subtypes and hypertension and possibilities of modulating
      pharmacologically vascular dopamine receptor function.

PMID- 21722094
TI  - The structural plasticity of the human copper chaperone for SOD1: insights from
      combined size-exclusion chromatographic and solution X-ray scattering studies.
AB  - The incorporation of copper into biological macromolecules such as SOD1 (Cu,Zn
      superoxide dismutase) is essential for the viability of most organisms. However,
      copper is toxic and therefore the intracellular free copper concentration is kept
      to an absolute minimum. Several proteins, termed metallochaperones, are charged
      with the responsibility of delivering copper from membrane transporters to its
      intracellular destination. The CCS (copper chaperone for SOD1) is the major
      pathway for SOD1 copper loading. We have determined the first solution structure
      of hCCS (human CCS) by SAXS (small-angle X-ray scattering) in conjunction with
      SEC (size-exclusion chromatography). The findings of the present study highlight
      the importance of this combined on-line chromatographic technology with SAXS,
      which has allowed us to unambiguously separate the hCCS dimer from other
      oligomeric and non-physiological aggregated states that would otherwise adversely
      effect measurements performed on bulk solutions. The present study exposes the
      dynamic molecular conformation of this multi-domain chaperone in solution. The
      metal-binding domains known to be responsible for the conveyance of copper to
      SOD1 can be found in positions that would expedite this movement. Domains I and
      III of a single hCCS monomer are able to interact and can also move into
      positions that would facilitate initial copper binding and ultimately transfer to
      SOD1. Conversely, the interpretation of our solution studies is not compatible
      with an interaction between these domains and their counterparts in an hCCS
      dimer. Overall, the results of the present study reveal the plasticity of this
      multi-domain chaperone in solution and are consistent with an indispensable
      flexibility necessary for executing its dual functions of metal binding and
      transfer.

PMID- 21722095
TI  - Pre-conditioning induces the precocious differentiation of neonatal astrocytes to
      enhance their neuroprotective properties.
AB  - Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I
      (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that
      astrocytes normally support neuronal survival and function, the purpose of the
      present study was to test the hypothesis that a hypoxic preconditioning stimulus
      would activate an adaptive astrocytic response. We analysed several functional
      parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2).
      Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of
      GFAP (glial fibrillary acidic protein)-positive cells with radial morphologies
      and the acquisition of multipolar GFAP-positive cells. Interestingly, many of
      these astrocytes had nuclear S100B. Accompanying their differentiation, there was
      increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino
      acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1)
      and ceruloplasmin. A subsequent H/I insult did not result in any further
      astrocyte activation. Some responses were cell autonomous, as levels of GS and
      MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In
      contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered.
      Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl
      cAMP), which mimicked several aspects of the preconditioning response, to
      determine whether activated astrocytes could protect neurons from subsequent
      excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter
      expression and function, and as hypothesized, protected neurons from glutamate
      excitotoxicity. Taken altogether, these results indicate that a preconditioning
      stimulus causes the precocious differentiation of astrocytes and increases the
      acquisition of multiple astrocytic functions that will contribute to the
      neuroprotection conferred by a sublethal preconditioning stress.

PMID- 21722096
TI  - Holding the uterine cervix may induce uterine contractions in atonic bleeding.

PMID- 21722097
TI  - Is routine hysteroscopy during LLETZ a valuable additional procedure?
AB  - We aimed to critically review our experience with the value and risks of a
      diagnostic hysteroscopy performed in addition to LLETZ. We retrospectively
      included 442 womentients undergoing LLETZ and additional routine diagnostic
      hysteroscopy. Women for whom concomitant diagnostic hysteroscopy was somehow
      indicated were excluded. We focused on complications and intrauterine
      abnormalities detected by hysteroscopy that had not been seen on preoperative
      vaginal ultrasound. In 28/442 (6.3%), hysteroscopy and/or histological
      examination of the specimen removed by curettage revealed an abnormal
      intrauterine finding (benign endometrial polyps, n=20; benign cervical polyps,
      n=2; small leiomyomas inside the uterine cavity, n=1;
      septate/arcuate/unicornuate, n=5). A total of 38 surgical complications (8.6%)
      occurred. The two adverse events related to diagnostic hysteroscopy were uterine
      perforations (0.5%). In conclusion, only a few benign findings of questionable
      clinical relevance were discovered. Thus, we do not consider an additional
      routine diagnostic hysteroscopy during LLETZ beneficial for the patient.

PMID- 21722098
TI  - Local infiltration analgesia in urogenital prolapse surgery: a prospective
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the analgesic effect of high-volume infiltration analgesia
      in urogenital prolapse surgery and provide a detailed description of the
      infiltration technique. DESIGN: A randomized, double-blind, placebo-controlled
      study following the CONSORT criteria. SETTING: A university hospital. PATIENTS:
      48 patients undergoing posterior wall repair and perineorraphy. METHODS: Patients
      received high-volume (26 ml) ropivacaine 1% with epinephrine (n=23) or saline
      (n=22) infiltration using a systematic technique ensuring uniform delivery to all
      tissues incised, handled or instrumented during the procedure. MAIN OUTCOME
      MEASURES: Pain and opioid requirements were assessed for 24 hours as well as time
      spent in the post-anesthesia care unit and time to first mobilization. RESULTS:
      Pain at rest, during coughing and movement was significantly reduced for the
      first four hours with the high-volume local anesthetic infiltration technique
      (p<0.001-0.006). Opioid requirements and time spent in the post-anesthesia care
      unit were significantly reduced in the ropivacaine group (p<0.001 and p<0.001,
      respectively) as well as the time to first mobilization (p<0.014). CONCLUSION:
      Systematic high-volume infiltration analgesia is an effective analgesic technique
      in patients undergoing posterior wall repair and perineorraphy, and improves
      early recovery.

PMID- 21722099
TI  - Immunohistochemical distinction of haematogones from B lymphoblastic
      leukaemia/lymphoma or B-cell acute lymphoblastic leukaemia (B-ALL) on bone marrow
      trephine biopsies: a study on 62 patients.
AB  - Haematogones are normal, maturing B-cell precursors. They can be confused with
      neoplastic immature lymphoid cells of B lymphoblastic leukaemia/lymphoma or B
      cell acute lymphoblastic leukaemia (B-ALL). Though multi-colour flow-cytometry
      strategies for distinguishing haematogones from cells of B-ALL are well
      described, similar strategies have not been determined for bone marrow trephine
      biopsies (BMTB). We revisited the morphological and immunohistochemical features
      (CD20, CD34, TdT and PAX5 expression) in 69 BMTB from 62 patients - 27 with
      excess haematogones; seven with residual B-ALL after therapy; 18 with no reported
      excess of haematogones or residual acute leukaemia on BMTB; and 17 diagnostic
      samples of B-ALL. The distinctive immunophenotypic pattern of BMTB with excess
      haematogones was of CD34, TdT, CD20 and PAX5 accounting for increasing
      proportions of cells in the order mentioned, whereas among B-ALL, the
      immunohistochemical pattern was of CD20, PAX5 and TdT accounting for an equal
      proportion of cells. Furthermore, among haematogones, the intensity of CD20
      expression was extremely heterogeneous as compared to the neoplastic cells in
      CD20-positive B-ALL. The TdT-positive haematogones were generally small and
      uniform, while a certain degree of heterogeneity was noticed among neoplastic B
      ALL cells. This study provides a practical strategy to distinguish haematogones
      from B-ALL cells in BMTB.

PMID- 21722100
TI  - What can we learn from old microdeletion syndromes using array-CGH screening?
AB  - Most microdeletion syndromes identified before the implementation of array
      comparative genomic hybridization (array-CGH) were presumed to be well-defined
      clinical entities. However, the introduction of whole-genome screening led not
      only to the description of new syndromes but also to the recognition of a broader
      spectrum of features for well-known syndromes. Here, we report on 10 patients
      presenting with mental retardation associated with atypical features not
      suggestive of a known microdeletion and a normal standard karyotype. Array-CGH
      analyses revealed five microdeletions in the DiGeorge region, three
      microdeletions in the Williams-Beuren region and two microdeletions in the Smith
      Magenis region. Reevaluation in these patients confirmed that the diagnosis
      remained difficult on clinical grounds and emphasized that well-known genomic
      disorders can have a phenotype that is heterogeneous and more variable than
      originally thought. The widespread use of array-CGH shows that such patients may
      be more readily achieved on the basis of genotype rather than phenotype.

PMID- 21722101
TI  - Age-related modification of antioxidant enzyme activities in relation to
      cardiovascular risk factors.
AB  - BACKGROUND: Since oxidative stress might cause and promote cardiovascular risk
      factors such as oxidized low-density lipoproteins (oxLDL), apolipoprotein(a)
      [apo(a)], asymmetric dimethylarginine (ADMA) and fetuin A, we investigated
      antioxidant enzyme activities in relation to the vascular redox balance and these
      risk factors in elderly people. MATERIALS AND METHODS: For this observational
      study, a total of 102 subjects were recruited and divided into three groups: A
      (70-74 years/n = 48), B (75-79 years/n = 35) and C (>= 80 years/n = 19).
      Activities of the erythrocyte antioxidant enzymes superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px) and catalase (CAT) were determined
      photometrically oxLDL, apo(a), ADMA and fetuin A by ELISA. Plasma concentrations
      of the lipid peroxidation products malondialdehyde (MDA) and conjugated dienes
      (CD) were analysed with HPLC. RESULTS: There were no significant age-associated
      alterations in apo(a) levels, but there was a significant age-related decrease in
      activities of SOD (A>C, B>C: P < 0.01), CAT (A>C: P < 0.05) and GSH-Px (A>C: P <
      0.05), accompanied by a significant increase in oxLDL (A<C: P < 0.001; B<C: P <
      0.05), ADMA (A<B: P < 0.05; A<C: P < 0.001), MDA (A<C, B<C: P < 0.01) and CD
      (A<C, B<C: P < 0.01), and a significant decrease in fetuin A (A>C: P < 0.01; B>C:
      P < 0.05). Consequently, all groups showed significant negative age-associated
      correlations between CAT and MDA (A, B, C: P < 0.05), GSH-Px and CD (A, C: P <
      0.01; B: P < 0.05), SOD and oxLDL (A, B: P < 0.05; C: P < 0.01), and fetuin A and
      MDA (A: P < 0.01; B, C: P < 0.05), and a significant positive correlation between
      oxLDL and ADMA (A, B: P < 0.05; C: P < 0.01). CONCLUSIONS: This study indicates a
      significant age-related decrease in antioxidant enzyme activities accompanied by
      significantly increased systemic oxidative stress, which promotes the
      cardiovascular risk factors oxLDL, ADMA and fetuin A in elderly people.

PMID- 21722102
TI  - Induction of interleukin-10 in the T helper type 17 effector population by the G
      protein coupled estrogen receptor (GPER) agonist G-1.
AB  - Interleukin-10 (IL-10) is a potent suppressor of the immune system, commonly
      produced by CD4(+) T cells to limit ongoing inflammatory responses minimizing
      host damage. Many autoimmune diseases are marked by large populations of
      activated CD4(+) T cells within the setting of chronic inflammation; therefore,
      drugs capable of inducing IL-10 production in CD4(+) T cells would be of great
      therapeutic value. Previous reports have shown that the small molecule G-1, an
      agonist of the membrane-bound G-protein-coupled estrogen receptor GPER,
      attenuates disease in an animal model of autoimmune encephalomyelitis. However,
      the direct effects of G-1 on CD4(+) T-cell populations remain unknown. Using ex
      vivo cultures of purified CD4(+) T cells, we show that G-1 elicits IL-10
      expression in T helper type 17 (Th17) -polarized cells, increasing the number of
      IL-10(+) and IL-10(+) IL-17A(+) cells via de novo induction of IL-10. T-cell
      cultures differentiated in the presence of G-1 secreted threefold more IL-10,
      with no change in IL-17A, tumour necrosis factor-alpha, or interferon-gamma.
      Moreover, inhibition of extracellular signal-regulated kinase (but not p38 or Jun
      N-terminal kinase) signalling blocked the response, while analysis of Foxp3 and
      RORgammat expression demonstrated increased numbers of IL-10(+) cells in both the
      Th17 (RORgammat(+)) and Foxp3(+) RORgammat(+) hybrid T-cell compartments. Our
      findings translated in vivo as systemic treatment of male mice with G-1 led to
      increased IL-10 secretion from splenocytes following T-cell receptor cross
      linking. These results demonstrate that G-1 acts directly on CD4(+) T cells, and
      to our knowledge provide the first example of a synthetic small molecule capable
      of eliciting IL-10 expression in Th17 or hybrid T-cell populations.

PMID- 21722103
TI  - Spatial anisotropy analyses of subcutaneous tissue layer: potential insights into
      its biomechanical characteristics.
AB  - As the intermediate layer between the muscle and skin, the subcutaneous tissue
      frequently experiences shear and lateral stresses whenever the body is in motion.
      However, quantifying such stresses in vivo is difficult. The lack of such
      measures is partly responsible for our poor understanding of the biomechanical
      behaviors of subcutaneous tissue. In this study, we employ both ultrasound
      imaging and a novel spatial anisotropy measure - incorporating Moran's I spatial
      autocorrelation calculations - to investigate the structuromechanical features of
      subcutaneous tissues within the extremities of 16 healthy volunteers. This
      approach is based on the understanding that spatial anisotropy can be an
      effective surrogate for the summative, tensile forces experienced by biological
      tissue. We found that spatial anisotropy in the arm, thigh and calf was
      attributed to the echogenic bands spanning the width of the ultrasound images. In
      both univariable and multivariable analyses, the calf was significantly
      associated with greater anisotropy compared with the thigh and arm. Spatial
      anisotropy was inversely related to subcutaneous thickness, and was significantly
      increased with longitudinally oriented probe images compared with transversely
      orientated images. Maximum peaks in spatial anisotropy were frequently observed
      when the longitudinally oriented ultrasound probe was swept across the extremity,
      suggesting that longitudinal channels with greater tension exist in the
      subcutaneous layer. These results suggest that subcutaneous biomechanical tension
      is mediated by collagenous/echogenic bands, greater in the calf compared with the
      thigh and arm, increased in thinner individuals, and maximal along longitudinal
      trajectories parallel to the underlying muscle. Spatial anisotropy analysis of
      ultrasound images has yielded meaningful patterns and may be an effective means
      to understand the biomechanical strain patterns within the subcutaneous tissue of
      the extremities.

PMID- 21722104
TI  - The role of transient dynamics in biological pest control: insights from a host
      parasitoid community.
AB  - 1. Identifying natural enemies that can maintain pests at low abundances is a
      priority in biological control. Here, we show that experiments combined with
      models generate new insights into identifying effective control agents prior to
      their release in the field. Using a host-parasitoid community (the harlequin bug
      and its egg parasitoids) as a model system, we report three key findings. 2. The
      interplay between the host's self-limitation and the parasitoids' saturating
      functional response causes the long-term (steady-state) outcomes for pest
      suppression to differ from those of short-term (transient) dynamics. When the
      bug's self-limitation is moderately strong, the parasitoid with the higher attack
      rate and conversion efficiency (Ooencyrtus) achieves greater host suppression in
      the long term, but its longer handling time causes long periods of transient
      dynamics during which the bug can reach high abundances; when the bug's self
      limitation is weak, host fluctuations amplify over time and Ooencyrtus fails at
      host suppression altogether. In contrast, the parasitoid with the lower attack
      rate and conversion efficiency but the shorter handling time (Trissolcus) induces
      only weak transient fluctuations of short duration and can maintain the host at
      low abundances regardless of the strength of the bug's self-limitation. 3.
      Release of multiple enemy species can compromise host suppression if an enemy
      that induces stronger transient fluctuations excludes one that induces weaker
      fluctuations. For instance, Ooencyrtus excludes Trissolcus despite having a
      longer handling time because of its higher conversion efficiency. The model
      correctly predicts the time to exclusion observed in experiments, suggesting that
      it captures the key biological features of the host-parasitoid interaction. 4.
      Intraspecific interference reduces long-term pest suppression but improves short
      term pest control by reducing the magnitude and duration of transient
      fluctuations. 5. These results highlight the importance of transient dynamics in
      pest suppression. Pests are unlikely to be strongly self-limited because they
      attack crop monocultures. Hence, pest fluctuations are likely to dominate short
      term dynamics even when the long-term outcome is a stable equilibrium. The
      tendency to induce strong transient fluctuations (e.g. through a long handling
      time) is therefore a crucial consideration when identifying effective pest
      control agents.

PMID- 21722105
TI  - Convergence of trophic interaction strengths in grassland food webs through
      metabolic scaling of herbivore biomass.
AB  - 1. Food web theory hypothesizes that trophic interaction strengths of consumers
      should vary with consumer metabolic body mass (mass(0.75) ) rather than simply
      with consumer body mass (mass(1.0) ) owing to constraints on consumption imposed
      by metabolic demand for and metabolic capacity to process nutrients and energy.
      Accordingly, species with similar metabolic body masses should have similar
      trophic interaction strengths. 2. We experimentally tested this hypothesis by
      assembling food webs comprised of species of arthropod predators, small sap
      feeding and large leaf-chewing insect herbivores and herbaceous plants in a New
      England, USA meadow grassland. The experiment comprised of a density-matching
      treatment where herbivore species were stocked into field mesocosms at equal
      densities to quantify baseline species identity and metabolic body mass effects.
      The experiment also comprised of a metabolic biomass-matching treatment where
      smaller sap-feeding herbivore (SH) species were stocked into mesocosms such that
      the product of their density and metabolic body mass (metabolic biomass) was
      equal to the large herbivore (LH) species. We compared the magnitude of the
      direct effects of herbivore species on plants in the different treatments. We
      also compared the magnitude of indirect effects between predators and plants
      mediated by herbivores in the different treatments. 3. Consistent with the
      hypothesis, we found that increasing metabolic biomass translated into a 9-14
      fold increase in magnitude of herbivore direct effects and up to a fivefold
      increase in indirect effects on plants. Moreover, metabolic biomass matching
      caused interaction strengths among herbivore species to converge. This result
      came about through increases in the herbivore mean effects as well as decreases
      in variation in effects among treatment replicates as herbivore metabolic biomass
      increased. 4. We found, however, that herbivore feeding mode rather than
      herbivore metabolic biomass explained differences in the sign of indirect effects
      in the different food webs. 5. We conclude that increasing herbivore metabolic
      biomass not only strengthened the direct and indirect effects on plants but also
      made those effects more consistent across space. Nevertheless, metabolic biomass
      alone could not completely explain variation in the nature of indirect effects in
      the food web, suggesting that additional consideration of consumer traits like
      feeding mode will provide a more nuanced understanding of trophic interaction
      strengths in food webs.

PMID- 21722106
TI  - Relative role of deterministic and stochastic determinants of soil animal
      community: a spatially explicit analysis of oribatid mites.
AB  - 1. Ecologists are debating the relative role of deterministic and stochastic
      determinants of community structure. Although the high diversity and strong
      spatial structure of soil animal assemblages could provide ecologists with an
      ideal ecological scenario, surprisingly little information is available on these
      assemblages. 2. We studied species-rich soil oribatid mite assemblages from a
      Mediterranean beech forest and a grassland. We applied multivariate regression
      approaches and analysed spatial autocorrelation at multiple spatial scales using
      Moran's eigenvectors. Results were used to partition community variance in terms
      of the amount of variation uniquely accounted for by environmental correlates
      (e.g. organic matter) and geographical position. Estimated neutral diversity and
      immigration parameters were also applied to a soil animal group for the first
      time to simulate patterns of community dissimilarity expected under neutrality,
      thereby testing neutral predictions. 3. After accounting for spatial
      autocorrelation, the correlation between community structure and key
      environmental parameters disappeared: about 40% of community variation consisted
      of spatial patterns independent of measured environmental variables such as
      organic matter. Environmentally independent spatial patterns encompassed the
      entire range of scales accounted for by the sampling design (from tens of cm to
      100 m). This spatial variation could be due to either unmeasured but spatially
      structured variables or stochastic drift mediated by dispersal. Observed levels
      of community dissimilarity were significantly different from those predicted by
      neutral models. 4. Oribatid mite assemblages are dominated by processes involving
      both deterministic and stochastic components and operating at multiple scales.
      Spatial patterns independent of the measured environmental variables are a
      prominent feature of the targeted assemblages, but patterns of community
      dissimilarity do not match neutral predictions. This suggests that either niche
      mediated competition or environmental filtering or both are contributing to the
      core structure of the community. This study indicates new lines of investigation
      for understanding the mechanisms that determine the signature of the
      deterministic component of animal community assembly.

PMID- 21722107
TI  - Submissions and authorship.

PMID- 21722108
TI  - Morphological and histological study of larval development of the Senegal sole
      Solea senegalensis: an integrative study.
AB  - This study provides a comprehensive description of the main morphological and
      histological events that take place during larval and post-larval development of
      Senegal sole Solea senegalensis in order to establish a reference for its normal
      developmental organogenesis. Five stages have been described. Before gill
      development at the onset of metamorphosis (eye migration process, stage 4c), the
      skin was the main site of gas and ion exchange, whereas during stages 3 and 4,
      the skin begins differentiating into the definitive juvenile structure. The
      timing of development of the endocrine system depends on each organ, the
      endocrine pancreas and thyroid gland being the first to differentiate (stages 2
      and 3, respectively), followed by the interrenal tissue and stannius corpuscles
      that develop at metamorphosis (stages 4 and 4c, respectively). The
      differentiation and maturation of the lymphohaematopoietic organs was coupled
      with the increase in complexity of the cardiovascular system and the presence of
      mature erythrocytes (stage 4b), which might be attributed to the change in
      respiration and the development of fully functional gills. In the differentiation
      of sensory structures, the development of eyes, inner ear, neuromasts and
      olfactory organs was rapid, with most of these organs becoming fully developed
      soon after hatching (stage 1). Vision, chemo- and mechano-reception developed
      very early in ontogeny, in parallel with the development of the central nervous
      system and changes in feeding habits. Although the general pattern of development
      in S. senegalensis appeared similar to most marine fish larvae already described,
      there were species-specific ontogenetic characteristics probably derived from the
      species' particular environment (subtropical waters) and behaviour (nocturnal,
      benthic, omnivorous feeding habits). These results on the organogenesis of larvae
      are a useful tool for establishing the functional systemic capabilities and
      physiological requirements of larvae to ensure optimal welfare and growth under
      aquaculture conditions.

PMID- 21722109
TI  - Olfactory discrimination of complex mixtures of amino acids by the black bullhead
      Ameiurus melas.
AB  - On the basis of previous findings of behavioural discrimination of amino acids
      and on the knowledge of electrophysiology of the catfish (genera Ictalurus and
      Ameiurus) olfactory organs, behavioural experiments that investigated olfactory
      discrimination of amino acid mixtures were carried out on the black bullhead
      Ameiurus melas. Repeated presentations of food-rewarded mixtures released
      increased swimming activity measured by counting the number of turns >90 degrees 
      within 90 s of stimulus addition. Non-rewarded amino acids and their mixtures
      released little swimming activity, indicating that A. melas discriminated between
      the conditioned and the non-conditioned stimuli. Two questions of mixture
      discrimination were addressed: (1) Are A. melas able to detect components within
      simple and complex amino acid mixtures? (2) What are the smallest differences
      between two complex mixtures that A. melas can detect? Three and 13 component
      mixtures tested were composed primarily of equipotent amino acids [determined by
      equal electroolfactogram (EOG) amplitude] that contained L-Cys at *100 the
      equipotent concentration. Ameiurus melas initially perceived the ternary amino
      acid mixture as its more stimulatory component alone [i.e. cysteine (Cys)],
      whereas the conditioned 13 component mixture containing the more stimulatory L
      Cys was perceived immediately as different from L-Cys alone. The results indicate
      that components of ternary mixtures are detectable by A. melas but not those of
      more complex mixtures. To test for the smallest detectable differences in
      composition between similar multimixtures, all mixture components were
      equipotent. Initially, A. melas were unable to discriminate the mixtures of six
      amino acids from the conditioned mixtures of seven amino acids, whereas they
      discriminated immediately the mixtures of four and five amino acids from the
      conditioned mixture. Experience with dissimilar mixtures enabled the A. melas to
      start discriminating the seven-component conditioned mixture from its six
      component counterparts. After fewer than five training trials, A. melas
      discriminated the mixtures of nine and 10 amino acids from a conditioned mixture
      of 12 equipotent amino acids; however, irrespective of the number of training
      trials, A. melas were unable to discriminate the 12 component mixture from its 11
      component counterparts.

PMID- 21722110
TI  - In vivo treatment with progestogens causes immunosuppression of carp Cyprinus
      carpio leucocytes by affecting nitric oxide production and arginase activity.
AB  - In this study, carp Cyprinus carpio were injected with various steroid compounds,
      including synthetic and natural progestogens and the glucocorticoid cortisol, to
      investigate effects on leucocytes isolated from their kidneys. Injection of
      cortisol led to an increased spleeno-somatic index (I(S)) on day 21 post
      injection (pi) and immunosuppressive effects measured as decreased nitric oxide
      (NO) production and increased arginase activity in isolated leucocytes on days 14
      and 21 pi, respectively. Moreover, reduced NO production was also observed after
      injection of the synthetic progestogens, levonorgestrel (LEV) and
      medroxyprogesterone acetate. In addition, LEV influenced arginase activity in
      head kidney cells on day 14 and day 21 pi. This study is the first demonstration
      in fishes that the application of these steroid compounds in vivo affects NO
      production and arginase activity of isolated leucocytes.

PMID- 21722111
TI  - Is the elusive Gymnothorax polyuranodon really a freshwater moray?
AB  - Analysis of 36 records of the rarely encountered moray Gymnothorax polyuranodon
      indicate that juveniles and adults inhabit fresh and mildly brackish habitats
      (salinity < 5) in streams of the Australian Wet Tropics Eighty-one per cent of
      these records were from freshwater streams and collectively demonstrate that this
      species inhabits fresh water throughout all seasons. A survey of fish
      researchers, each with at least 100 h of field experience in Australia's Wet
      Tropics, revealed that 33% of researchers working in fresh waters (nine of 27
      researchers) had encountered the species and 15% of researchers with substantial
      experience working in estuaries (two of 13 researchers) had encountered the
      species. The species was not sampled or observed in the nearshore marine
      environment. The only record of an elver of this species was, however, found in
      an estuary at a salinity of 33.4. This preliminary evidence suggests adult G.
      polyuranodon occupy freshwater habitats, but further research is required to
      understand the complete life cycle, including movements, habitat use and
      reproductive ecology of the species.

PMID- 21722112
TI  - Preliminary data on the influence of rearing temperature on the growth and
      reproductive status of fathead minnows Pimephales promelas.
AB  - An investigation into the influence of temperature on the growth and reproductive
      status of the fathead minnow Pimephales promelas revealed that, while there was
      no clear effect of treatment on sex differentiation, ovarian tissue from female
      fish reared under the highest temperature regime contained large amounts of
      undefined tissue containing no germ cells. Furthermore, both male and female fish
      exhibited differences in length mass, condition and somatic indices, and in the
      expression of secondary sexual characteristics. The patterns observed are
      discussed in the context of climate change.

PMID- 21722113
TI  - Diet and feeding niches of juvenile Gadus morhua, Melanogrammus aeglefinus and
      Merlangius merlangus during the settlement transition in the northern North Sea.
AB  - A study on the feeding ecology of juvenile cod Gadus morhua, haddock
      Melanogrammus aeglefinus and whiting Merlangius merlangus during the pelagic to
      demersal transition was carried out on fishes sampled throughout their settlement
      season at a local nursery ground in the north-western North Sea, off the Scottish
      east coast. A comprehensive quantitative taxonomic analysis of the diets, as
      described in the paper, showed the emergence of distinctive feeding niches,
      minimizing the potential for competition between species and size categories. The
      diet of the juveniles changed with fish size, water depth, time of year and
      distance offshore. Small G. morhua were present in the study area earlier in the
      season, settled further inshore and ate a higher proportion of pelagic prey
      (copepods) and as size increased they moved into deeper waters and targeted
      larger, more benthic prey. As M. aeglefinus grew larger and moved into deeper
      waters, a diet of largely copepods, amphipods, pelagic Ammodytes spp., cyprids
      and pelagic gastropods evolved to one dominated predominantly by fishes and
      benthic invertebrates. In the case of M. merlangus, widespread ages and sizes
      throughout the sampling season, a consequence of their more protracted spawning
      season, resulted in dietary changes which were more likely to be influenced by
      seasonal changes in the prey field, in addition to developmental (size) changes,
      than the diets of the other two species.

PMID- 21722114
TI  - Identification of seagrasses in the gut of a marine herbivorous fish using DNA
      barcoding and visual inspection techniques.
AB  - Traditional visual diet analysis techniques were compared with DNA barcoding in
      juvenile herbivorous rabbitfish Siganus fuscescens collected in Moreton Bay,
      Australia, where at least six species of seagrass occur. The intergenic spacer
      trnH-psbA, suggested as the optimal gene for barcoding angiosperms, was used for
      the first time to identify the seagrass in fish guts. Four seagrass species and
      one alga were identified visually from gut contents; however, there was
      considerable uncertainty in visual identification with 38 of 40 fish having
      unidentifiable plant fragments in their gut. PCR and single-strand conformational
      polymorphism (SSCP) were able to discriminate three seagrass families from
      visually cryptic gut contents. While effective in identifying cryptic gut content
      to family level, this novel method is likely to be most efficient when paired
      with visual identification techniques.

PMID- 21722115
TI  - Genetic population structure of perch Perca fluviatilis along the Swedish coast
      of the Baltic Sea.
AB  - In this study, the genetic variation of perch Perca fluviatilis from 18 different
      sites along the Swedish coast of the Baltic Sea was assessed. There was a
      relative strong support for isolation by distance and the results suggest an
      overall departure from panmixia. The level of genetic divergence was moderate
      (global F(ST) = 0.04) and indications of differences in the population genetic
      structure between the two major basins (central Baltic Sea and Gulf of Bothnia)
      in the Baltic Sea were found. There was a higher level of differentiation in the
      central Baltic Sea compared to the Gulf of Bothnia, and the results suggest that
      stretches of deep water might act as barriers to gene flow in the species. On the
      basis of the estimation of genetic patch size, the results corroborate previous
      mark--recapture studies and suggest that this is a species suitable for local
      management. In all, the findings of this study emphasize the importance of
      considering regional differences even when strong isolation by distance
      characterize the genetic population structure of species.

PMID- 21722116
TI  - The diet of toothfish species Dissostichus eleginoides and Dissostichus mawsoni
      with overlapping distributions.
AB  - The diets of Antarctic toothfish Dissostichus mawsoni and Patagonian toothfish
      Dissostichus eleginoides were examined around the South Sandwich Islands in the
      Southern Ocean, one of few regions with overlapping populations of the two
      species. Despite large differences in the proportion of stomachs containing prey
      (76.2% of D. mawsoni compared to 7.2% of D. eleginoides), diet composition was
      broadly similar (Schoener overlap index of 74.4% based on prey mass) with
      finfishes (particularly macrourids and muraenolepidids) and cephalopods (mainly
      Kondakovia longimana) comprising >90% of the prey mass of both species. Predation
      rates of the main fish prey, as mean counts per stomach sampled, were spatially
      correlated with their relative abundance around the islands derived from fishery
      by-catch data, suggesting a general lack of prey selectivity. This study supports
      the view that bathyal Dissostichus are opportunistic carnivores and finds that D.
      mawsoni and D. eleginoides occupy a similar trophic niche and are likely to
      compete for prey in regions where both are distributed. The large increase in
      rate of prey occurrence and size of prey in D. mawsoni stomachs relative to D.
      eleginoides suggests, however, species differences in feeding behaviour, which
      may reflect the increased metabolic demands of a cold-water adapted physiology.
      [Correction added after online publication 13 June 2011: spelling of species name
      corrected].

PMID- 21722117
TI  - Variable stocking effect and endemic population genetic structure in Murray cod
      Maccullochella peelii.
AB  - Microsatellite markers were utilized to examine the genetic structure of Murray
      cod Maccullochella peelii throughout its distribution in the Murray--Darling
      Basin (MDB) of eastern Australia, and to assess the genetic effects of over three
      decades of stocking hatchery-reared fingerlings. Bayesian analysis using the
      programme Structure indicated that the species is largely genetically panmictic
      throughout much of its extensive range, most probably due to the high level of
      connectivity between catchments. Three catchments with terminal wetlands (the
      Lachlan, Macquarie and Gwydir), however, contained genetically distinct
      populations. No stocking effects were detected in the catchments that were
      genetically panmictic (either because of low genetic power or lack of effects),
      but the genetically differentiated Gwydir and Macquarie catchment populations
      were clearly affected by stocking. Conversely, there was no genetic evidence for
      survival and reproduction of stocked fish in the Lachlan catchment. Therefore,
      stocking of M. peelii throughout the MDB has resulted in a range of genetic
      effects ranging from minimal detectable effect, to substantial change in wild
      population genetic structure.

PMID- 21722118
TI  - Expression pattern of heat shock protein 90 gene of humphead snapper Lutjanus
      sanguineus during pathogenic Vibrio harveyi stress.
AB  - The full-length cDNA of heat shock protein 90 (HSP90) of humphead snapper
      Lutjanus sanguineus, designated as rsHSP90, was cloned by rapid amplification of
      complementary (c)DNA ends (RACE) techniques with the primers designed from the
      known expressed sequence tag (EST) sequence identified from the subtracted cDNA
      library of the head kidney of L. sanguineus. Sequence analysis showed that the
      full-length cDNA of rsHSP90 was 2745 bp, containing a 5' terminal untranslated
      region (UTR) of 99 bp, a 3' terminal UTR of 471 bp and an open reading frame
      (ORF) of 2175 bp encoding a polypeptide of 725 amino acids. On the basis of the
      deduced amino acid sequence, the theoretical molecular mass of rsHSP90 was
      calculated to be 83.18 kDa with an isoelectric point of 4.79. Moreover, five
      classical HSP90 family signatures were found in the amino acids sequence of
      rsHSP90 by PredictProtein. Basic local-alignment search-tool (BLAST) analysis
      revealed that the amino acids sequence of rsHSP90 had the highest similarity of
      97% when compared with other HSP90s. Fluorescent real-time quantitative reverse
      transcription (RT)-PCR was used to examine the expression pattern of rsHSP90 in
      eight kinds of tissues and organs of L. sanguineus challenged with Vibrio
      harveyi. There was a clear time-dependent expression pattern of rsHSP90 in head
      kidney, spleen and thymus after bacterial challenge and the expression of
      messenger (m)RNA reached the maximum level at the time points of 9, 15 and 24 h,
      respectively. The up-regulated mRNA expression of rsHSP90 in L. sanguineus after
      bacterial challenge indicated that rsHSP90 was inducible and might be involved in
      immune response.

PMID- 21722119
TI  - The impact of social context on male mate preference in a unisexual--bisexual
      mating complex.
AB  - Male sailfin mollies Poecilia latipinna were tested in five different treatments
      that varied in the relative frequency of heterospecific gynogens (Amazon molly
      Poecilia formosa) to conspecific females to determine whether social interactions
      among males within a population causes some males to mate with heterospecific
      females. Male P. latipinna inseminated a significantly higher proportion of
      conspecific females and fertilized a significantly higher number of conspecific
      eggs regardless of the treatment. Nonetheless, preference for conspecific females
      was not exclusive as a range of 20 to 50% of heterospecific females were
      fertilized. Social interactions among males may best explain the results and may
      therefore play an important role in the maintenance of unisexual--bisexual mating
      complexes.

PMID- 21722120
TI  - Scavenging interactions between the arrow tooth eel Synaphobranchus kaupii and
      the Portuguese dogfish Centroscymnus coelolepis.
AB  - A scavenging interaction between the arrow tooth eel Synaphobranchus kaupii and
      the Portuguese dogfish Centroscymnus coelolepis, both ubiquitous components of
      fish assemblages at bathyal depths, was observed. Using a baited camera between
      1297 and 2453 m in the eastern Atlantic Ocean continental slope, it was shown
      that despite consistently rapid arrival times of S. kaupii (<5 min), their
      feeding bouts (indicated by acute peak in numbers) did not take place until
      shortly after C. coelolepis arrived and removed the exterior surface of the bait
      (skipjack tuna Katsuwonus pelamis carcass). Change in the numbers of S. kaupii
      was hence dependent on the arrival of a more powerful scavenger throughout the
      study site, and at the deeper stations where the population of C. coelolepis
      declined, S. kaupii was observed to be present but waited for >2 h before
      feeding, thus contradicting conventional scavenging assumptions in the presence
      of a food fall.

PMID- 21722121
TI  - The relative influence of local to regional drivers of variation in reef fishes.
AB  - In this study, fishes and habitat attributes were quantified, four times over 1
      year, on three reefs within four regions encompassing a c. 6 degrees  latitudinal
      gradient across south-western Australia. The variability observed was partitioned
      at these spatio-temporal scales in relation to reef fish variables and the
      influence of environmental drivers quantified at local scales, i.e. at the scale
      of reefs (the number of small and large topographic elements, the cover of kelp,
      fucalean and red algae, depth and wave exposure) and at the scale of regions
      (mean and maximum nutrient concentrations and mean seawater temperature) with
      regard to the total abundance, species density, species diversity and the
      multivariate structure of reef fishes. Variation in reef fish species density and
      diversity was significant at the regional scale, whereas variation in the total
      abundance and assemblage structure of fishes was also significant at local
      scales. Spatial variation was greater than temporal variation in all cases. A
      systematic and gradual species turnover in assemblage structure was observed
      between adjacent regions across the latitudinal gradient. The cover of red algae
      within larger patches of brown macroalgae (a biological attribute of the reef)
      and the number of large topographic elements (a structural attribute of the reef)
      were correlated with variation observed at local scales, while seawater
      temperature correlated with variation at the scale of regions. In conclusion,
      conservation efforts on reef fishes need to incorporate processes operating at
      regional scales with processes that shape local reef fish communities at local
      scales.

PMID- 21722122
TI  - Comparative metabolic rates of common western North Atlantic Ocean sciaenid
      fishes.
AB  - The resting metabolic rates (R(R)) of western North Atlantic Ocean sciaenids,
      such as Atlantic croaker Micropogonias undulatus, spot Leiostomus xanthurus and
      kingfishes Menticirrhus spp., as well as the active metabolic rates (R(A)) of M.
      undulatus and L. xanthurus were investigated to facilitate inter and
      intraspecific comparisons of their energetic ecology. The R(R) of M. undulatus
      and L. xanthurus were typical for fishes with similar lifestyles. The R(R) of
      Menticirrhus spp. were elevated relative to those of M. undulatus and L.
      xanthurus, but below those of high-energy-demand species such as tunas Thunnus
      spp. and dolphinfish Coryphaena hippurus. Repeated-measures non-linear mixed
      effects models were applied to account for within-individual autocorrelation and
      corrected for non-constant variance typical of noisy R(A) data sets. Repeated
      measures models incorporating autoregressive first-order [AR(1)] and
      autoregressive moving average (ARMA) covariances provided significantly superior
      fits, more precise parameter estimates (i.e. reduced s.e.) and y-intercept
      estimates that more closely approximated measured R(R) for M. undulatus and L.
      xanthurus than standard least-squares regression procedures.

PMID- 21722123
TI  - Indices of stress in three-spined sticklebacks Gasterosteus aculeatus in relation
      to extreme weather events and exposure to wastewater effluent.
AB  - Whole-body concentrations of cortisol and glucose were measured in three-spined
      sticklebacks Gasterosteus aculeatus from two rivers (Rivers Ray and Ock) in
      southern England during a 30 month period in order to assess effects on the
      stress axis of (1) remediation of a wastewater treatment works (WWTW) effluent
      (River Ray) and (2) episodic changes in flow rate arising from periods of high
      rainfall (Rivers Ray and Ock). The postcapture concentrations of cortisol and
      glucose in fish from both rivers did not exhibit a seasonal periodicity but did
      show significant between-sample, between-site and between-river variation,
      superimposed upon a consistent downward trend for each analyte during the
      monitoring period. Corticosteroid and glucose concentrations following capture
      were inversely linked with a progressive increase in condition of the fish during
      this period. Site-dependent trends possibly related to exposure to the WWTW
      effluent were detected for both analytes in fish from the River Ray. For fish in
      the River Ray, a significant proportion of variation in both corticosteroid and
      glucose concentrations, additional to the downward trend with time, was accounted
      for by temporal proximity of the sample to exceptional flow events arising from
      episodes of high rainfall and high turbidity. This relationship was not
      statistically significant for fish from the River Ock. These data suggest that
      the responsiveness of the stress axis in free-living G. aculeatus may be altered
      by exposure to WWTW effluent and by exposure to physical changes in the aquatic
      environment such as those arising from extreme weather events. The magnitude of
      these effects may be increased by exposure to both stressors concurrently.

PMID- 21722124
TI  - Structure and function of the velar muscle in the New Zealand hagfish Eptatretus
      cirrhatus: response to temperature change and hypoxia.
AB  - The rate of velar movement in Eptatretus cirrhatus, as determined by
      electromyography, increased with Q(10) 3.2 during exposure to temperatures
      between 7 and 19 degrees  C and increased 3.9 fold during exposure to hypoxia
      (oxygen partial pressure = 6.67 kPa). This confirms the role of the velum in
      generating respiratory currents and modification of its activity in response to
      changes in metabolic demand or environmental oxygen availability. The maximum
      velar rate observed was 168 beats min(-1) , higher than that recorded in any
      hagfish species to date. Fibres of musculus craniovelaris were exclusively small,
      red (slow-twitch) fibres, consistent with a high aerobic capacity required by
      fibres involved in rhythmic, ongoing activity.

PMID- 21722125
TI  - Foraging success of juvenile pike Esox lucius depends on visual conditions and
      prey pigmentation.
AB  - Young-of-the-year pike Esox lucius foraging on copepods experienced different
      foraging success depending on prey pigmentation in water visually degraded by
      brown colouration or algae. Both attack rate and prey consumption rate were
      higher for E. lucius foraging on transparent prey in brown water, whereas the
      opposite was true in algal turbid water. Pigments in copepod prey may have a
      cryptic function in brown water instead of a photo-protective function even if
      prey-size selectivity was stronger than selection based on pigmentation in
      juvenile E. lucius.

PMID- 21722126
TI  - The reproductive cycle of the roundel skate Raja texana.
AB  - The reproductive cycle of Raja texana was determined from 63 females (510-630 mm
      total length, L(T)) and 81 males (355-546 mm L(T)) collected from the Gulf of
      Mexico. The results, based on follicle size, mature spermatocysts and
      gonadosomatic index (I(G)) suggests year-round reproductive activity.

PMID- 21722132
TI  - Neurochemokines: a menage a trois providing new insights on the functions of
      chemokines in the central nervous system.
AB  - Recent observations suggest that besides their role in the immune system,
      chemokines have important functions in the brain. There is a great line of
      evidence to suggest that chemokines are a unique class of
      neurotransmitters/neuromodulators, which regulate many biological aspects as
      diverse as neurodevelopment, neuroinflammation and synaptic transmission. In
      physiopathological conditions, many chemokines are synthesized in activated
      astrocytes and microglial cells, suggesting their involvement in brain defense
      mechanisms. However, when evoking chemokine functions in the nervous system, it
      is important to make a distinction between resting conditions and various
      pathological states including inflammatory diseases, autoimmune or
      neurodegenerative disorders in which chemokine functions have been extensively
      studied. We illustrate here the emergent concept of the
      neuromodulatory/neurotransmitter activities of neurochemokines and their
      potential role as a regulatory alarm system and as a group of messenger molecules
      for the crosstalk between neurons and cells from their surrounding
      microenvironment. In this deliberately challenging review, we provide novel
      hypotheses on the role of these subtle messenger molecules in brain functions
      leading to the evidence that previous dogmas concerning chemokines should be
      reconsidered.

PMID- 21722133
TI  - Between promiscuity and specificity: novel roles of EF-hand calcium sensors in
      neuronal Ca2+ signalling.
AB  - In recent years, substantial progress has been made towards an understanding of
      the physiological function of EF-hand calcium sensor proteins of the Calmodulin
      (CaM) superfamily in neurons. This deeper appreciation is based on the
      identification of novel target interactions, structural studies and the discovery
      of novel signalling mechanisms in protein trafficking and synaptic plasticity, in
      which CaM-like sensor proteins appear to play a role. However, not all
      interactions are of plausible physiological relevance and in many cases it is not
      yet clear how the CaM signaling network relates to the proposed function of other
      EF-hand sensors. In this review, we will summarize these findings and address
      some of the open questions on the functional role of EF-hand calcium binding
      proteins in neurons.

PMID- 21722134
TI  - Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits
      experimental periodontitis in rats.
AB  - BACKGROUND AND OBJECTIVE: The complement activation product 5a (C5a) is a potent
      mediator of the innate immune response to infection, and may thus also
      importantly determine the development of periodontitis. The present study was
      designed to explore the effect of several novel, potent and orally active C5a
      receptor (CD88) antagonists (C5aRAs) on the development of ligature-induced
      periodontitis in an animal model. MATERIAL AND METHODS: Three different cyclic
      peptide C5aRAs, termed PMX205, PMX218 and PMX273, were investigated. Four groups
      of Wistar rats (n = 10 in each group) were used. Starting 3 d before induction of
      experimental periodontitis, rats either received one of the C5aRas (1-2 mg/kg) in
      the drinking water or received drinking water only. Periodontitis was assessed
      when the ligatures had been in place for 14 d. RESULTS: Compared with control
      rats, PMX205- and PMX218-treated rats had significantly reduced periodontal bone
      loss. CONCLUSION: The findings suggest that complement activation, and
      particularly C5a generation, may play a significant role in the development and
      progression of periodontitis. Blockade of the major C5a receptor, CD88, with
      specific inhibitors such as PMX205, may offer novel treatment options for
      periodontitis.

PMID- 21722135
TI  - Topical and intermittent application of parathyroid hormone recovers alveolar
      bone loss in rat experimental periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis is characterized by periodontal tissue
      inflammation and alveolar bone loss. The intermittent administration of
      parathyroid hormone (PTH), a major regulator of bone remodeling, has been
      demonstrated to stimulate osteoblastic activity. Although the systemic
      administration of PTH has been reported to protect against periodontitis
      associated bone loss, the effect of the topical administration of PTH is unclear.
      In this study, the effect of intermittent administration of PTH on osteoblastic
      differentiation was examined in cultured calvaria cells and then the effect of
      topical and intermittent administration of PTH was determined by measuring the
      recovery of alveolar bone loss after inducing experimental periodontitis in rats.
      MATERIAL AND METHODS: Alkaline phosphatase activity and bone nodule formation
      were measured in fetal rat calvaria cells. Experimental periodontitis was induced
      by placing nylon ligature around rat maxillary molars for 20 d. After ligature
      removal (day 0), PTH was topically injected into buccal gingiva three times a
      week for 10 wk. Micro-computed tomography analysis and histological examination
      were performed on days 35 and 70. RESULTS: Intermittent exposure of PTH in
      calvaria cells increased alkaline phosphatase activity and bone nodule formation
      by 1.4- and 2.4-fold, respectively. Ligature procedures induced marked alveolar
      bone loss around the molars on day 0 and greater bone recovery was observed in
      the PTH-treated rats on day 70. An increase in osteoid formation on the surface
      of alveolar bone was detected in the PTH-treated rats. CONCLUSION: Intermittent
      treatment with PTH stimulated osteoblastic differentiation in fetal rat calvaria
      cell cultures, and topical and intermittent administration of PTH recovered
      alveolar bone loss in rat experimental periodontitis.

PMID- 21722136
TI  - Working memory and response inhibition in children and adolescents: age and
      organization issues.
AB  - The aim of the present study was to examine the role of age in the organization
      of verbal working memory, visuospatial working memory and inhibition;
      specifically whether these constructs could be considered unitary or separate in
      children aged 7 to 12 years (n = 164) and in adolescents aged 13 to 16 years (n =
      75) using a multi-group confirmatory factor analysis. Results suggested that
      verbal working memory, visuospatial working memory and inhibition improved from
      childhood to adolescence. However, improvement was not followed by a change in
      the organization of these components. Verbal working memory, visuospatial working
      memory and inhibition constituted separable but associated constructs in children
      and in adolescents.

PMID- 21722137
TI  - Validation of the Revised Illness Perception Questionnaire (IPQ-R) in a sample of
      persons recovering from myocardial infarction--the Swedish version.
AB  - When people's health is threatened, they generally develop illness perceptions to
      make sense of their illness. The Illness Perception Questionnaire (IPQ-R),
      developed by Moss-Morris et al (2002), has been widely used in many countries to
      measure such representations. However, since studies in this crucial research
      area are lacking in Sweden a Swedish version of IPQ-R was validated with a focus
      on the seven subscales: timeline acute/chronic, timeline cyclical, consequences,
      personal control, treatment control, illness coherence and emotional
      representations. Using confirmatory factor analysis, the aim of the present study
      was to validate the internal structure of the Swedish version in a sample of 202
      persons (144 men and 58 women) who had been diagnosed with myocardial infarction
      four months earlier. Additionally, inter-correlations among the seven subscales
      and external concurrent validity were also investigated. The results of
      confirmatory factor analysis revealed that, in line with the English version of
      the IPQ-R, the specified seven-factor model had a satisfactory fit. One item was
      however not considered reliable and was therefore excluded from the instrument.
      The internal consistency (Cronbach's alpha coefficients) and the inter-factor
      correlations were relatively similar to those reported in the validation study of
      the original English IPQ-R. In tests of concurrent validity, the seven IPQ-R
      subscales were, as hypothesized, mainly associated with external variables. To
      conclude, the Swedish version of the IPQ-R's seven dimensions, with one item
      removed, (total 37 items) was found to be a reliable and valid measure of illness
      perception.

PMID- 21722138
TI  - Disease severity and quality of life in a follow-up study of patients with
      occupational contact dermatitis.
AB  - BACKGROUND: Few studies have investigated how occupational contact dermatitis and
      its severity affect patients' quality of life (QoL). OBJECTIVES: To investigate
      the impact of occupational contact dermatitis and its severity on patients' QoL,
      and to examine the association between different QoL measures. METHOD: Patients
      previously diagnosed with occupational contact dermatitis completed the Short
      Form Health Survey (SF-36) and Dermatology Life Quality Index (DLQI). Disease
      severity was rated both by the patient and by the physician. RESULTS: Of a
      possible 725, a total of 119 patients (16.4%) were included in the study, and, at
      follow-up, just over 21% had normal skin and 18.3% had progressed to persistent
      dermatitis. The SF-36 median physical component summary score was 52
      [interquartile range (IQR): 43-56] and the mental component summary median score
      was 51 (IQR: 44-57). The correlation between patient-rated and physician-rated
      disease severity was moderate (r = 0.708, p < 0.00001). The correlation between
      the disease severity measures and DLQI was moderate, whereas the SF-36 correlated
      poorly with both the DLQI and disease severity measures. CONCLUSIONS: QoL was
      generally reduced in this group of patients with occupational contact dermatitis,
      with some correlation between severity and DLQI. The DLQI was a more sensitive
      measurement of QoL than the SF-36 in this patient population. Incorporating
      disease severity rating with a QoL questionnaire is valuable in occupational
      contact dermatitis and is recommended.

PMID- 21722139
TI  - Black tattoo inks are a source of problematic substances such as dibutyl
      phthalate.
AB  - BACKGROUND: Tattooing has recently become increasingly popular. Using tiny
      needles, tattooists place the tattoo ink in the dermis along with numerous
      unknown ingredients. Most tattoos consist of black inks, which are predominantly
      composed of soot products (carbon black with polycyclic aromatic hydrocarbons).
      OBJECTIVES: Black tattoos cause skin problems, including allergic reactions, but
      the responsible substance frequently remains unknown. MATERIAL/METHODS: We
      applied gas chromatograph-mass spectrometry analysis to search for hazardous
      compounds in 14 different commercially available black tattoo ink samples.
      RESULTS: The analysis revealed that all inks contained the softener substance
      dibutyl phthalate (0.12-691.2 ug/g). Some of the inks contained hexachloro-1,3
      butadiene (0.08-4.52 ug/g), metheneamine (0.08-21.64 ug/g), dibenzofuran (0.02
      1.62 ug/g), benzophenone (0.26-556.66 ug/g), and 9-fluorenone (0.04-3.04 ug/g).
      CONCLUSION: The sensitizing agent dibutyl phthalate acts directly on
      keratinocytes and can drive Th2 responses following skin exposure via induction
      of thymic stromal lymphopoietin gene expression. Hexachloro-1,3-butadiene is
      genotoxic in vitro and 9-fluorenone is cytotoxic, generating reactive oxygen
      species under light exposure. The substances found in the inks might be partially
      responsible for adverse skin reactions to tattoos.

PMID- 21722140
TI  - Papaverine chloride as a topical vasodilator in accidental injection of
      adrenaline into a digital finger.

PMID- 21722141
TI  - Evaluating the negative predictive value of provocation tests with nonsteroidal
      anti-inflammatory drugs.
AB  - BACKGROUND: The nonsteroidal anti-inflammatory drugs (NSAIDs) hypersensitivity
      work-up is based on clinical history, skin tests, and drug provocation tests. The
      negative predictive value (NPV) of the latter is not established. METHOD: A
      cohort study was conducted in the Allergy Department in Montpellier to evaluate
      the NPV of the provocation test with NSAIDs in patients with clinical
      presentation suggestive of hypersensitivity, and negatively tested. Patients were
      contacted at least 6 months after the work-up. Patients who took NSAID and
      reacted were proposed a new allergy work-up, which included a provocation test
      with the culprit drug. RESULTS: Among the 393 patients contacted, 279 (71.0%)
      were followed up. Two hundred and sixty (93.2%) patients had taken a NSAID at
      least once: 139 (53.5%) the same drug as the one tested and 215 (82.7%) an
      alternative (94, 33.7% taking both the tested NSAID and an alternative). Eight
      patients (3.1%) reported a reaction (five with the negatively tested NSAID and
      three with another NSAID). All the reactions occurred immediately after the first
      administration and were not severe. Among the five patients who reacted with the
      negatively tested NSAID, only three accepted a re-challenge, negative in two
      cases and positive in one, representing a NPV of 97.8% (95% CI: 95.4-100%). Three
      patients (3/215) reported a reaction when an alternative NSAID was taken,
      representing a NPV of 98.6% (95% CI: 97-100%). CONCLUSION: The NPV of NSAIDs drug
      provocation test is high. This should reassure physicians who might hesitate to
      prescribe NSAIDs, especially in patients with negative allergic work-ups.

PMID- 21722142
TI  - Water stress, shoot growth and storage of non-structural carbohydrates along a
      tree height gradient in a tall conifer.
AB  - We analysed concentrations of starch, sucrose, glucose and fructose in upper
      branch wood, foliage and trunk sapwood of Douglas-fir trees in height classes
      ranging from ~2 to ~57 m. Mean concentrations of non-structural carbohydrates
      (NSC) for all tissues were highest in the tallest height class and lowest in the
      lowest height class, and height-related trends in NSC were most pronounced in
      branches. Throughout a 17-month sampling period, mean values of branch NSC from
      the 57 m trees ranged between 30 and 377% greater than the 2 m trees. Branch NSC
      was inversely correlated with midday shoot water potential (Psi(l)), shoot
      osmotic potential at full turgor (Psi) and shoot extension. Temporal fluctuation
      in branch NSC was inversely correlated with height, and positively correlated
      with midday Psi(l) , Psi and shoot extension. The positive correlation between
      height and storage of NSC, and the negative correlation between NSC storage and
      shoot extension provide evidence that size-related growth decline in trees is not
      strongly associated with constraints on photosynthesis. The negative correlation
      between height and fluctuation in NSC suggests that mobilization of photosynthate
      in taller trees is constrained by some factor such as reductions in turgor-driven
      cell expansion or constraints on phloem transport.

PMID- 21722143
TI  - Beyond the genome: recent advances in Toxoplasma gondii functional genomics.
AB  - Recent years have witnessed an explosion in the amount of genomic information
      available for Toxoplasma gondii and other closely related pathogens. These data,
      many of which have been made publicly available prior to publication, have
      facilitated a wide variety of functional genomics studies. In this review, we
      provide a brief overview of existing database tools for querying the Toxoplasma
      genome and associated genome-wide data and review recent publications that have
      been facilitated by these data. Topics covered include strain comparisons and
      quantitative trait loci mapping, gene expression analyses during the cell cycle
      as well as during parasite differentiation, and proteomics.

PMID- 21722144
TI  - Immunologically based control strategies for ostertagiosis in cattle: where do we
      stand?
AB  - Ostertagia ostertagi is one of the most important gastrointestinal parasites
      infecting millions of cattle in temperate climate areas. Because infection leads
      to significant losses in productivity, farmers are pushed, because of the on
      going intensification of the livestock production systems, to frequently
      administer anthelmintics to minimize the exposure of their animals to this
      parasite. However, whether such approach is sustainable in the long term,
      especially in an era of emerging drug resistance and global climatic changes, is
      still a matter of debate. Immunological control of worm infections through
      vaccination is often put forward as the most rational and cost-effective
      alternative for anthelmintics to control helminth infections. However, the
      development of an immunologically based control strategy requires a thorough
      knowledge of the host-parasite interactions, the immune responses involved and
      the biology of the parasite itself. The aim of this review is to consolidate
      information available in these areas, specifically for O. ostertagi, and identify
      some critical gaps in our current knowledge.

PMID- 21722146
TI  - Emergence and spread of antibiotic resistance following exposure to antibiotics.
AB  - Within a susceptible wild-type population, a small fraction of cells, even <10(
      9) , is not affected when challenged by an antimicrobial agent. This
      subpopulation has mutations that impede antimicrobial action, allowing their
      selection during clinical treatment. Emergence of resistance occurs in the frame
      of a selective compartment termed a mutant selection window (MSW). The lower
      margin corresponds to the minimum inhibitory concentration of the susceptible
      cells, whereas the upper boundary, named the mutant prevention concentration
      (MPC), restricts the growth of the entire population, including that of the
      resistant mutants. By combining pharmacokinetic/pharmacodynamic concepts and an
      MPC strategy, the selection of resistant mutants can be limited. Early treatment
      avoiding an increase of the inoculum size as well as a regimen restricting the
      time within the MSW can reduce the probability of emergence of the resistant
      mutants. Physiological and, possibly, genetic adaptation in biofilms and a high
      proportion of mutator clones that may arise during chronic infections influence
      the emergence of resistant mutants. Moreover, a resistant population can emerge
      in a specific selective compartment after acquiring a resistance trait by
      horizontal gene transfer, but this may also be avoided to some extent when the
      MPC is reached. Known linkage between antimicrobial use and resistance should
      encourage actions for the design of antimicrobial treatment regimens that
      minimize the emergence of resistance. Emergence of a resistant bacterial
      subpopulation within a susceptible wild-type population can be restricted with a
      regimen using an antibiotic dose that is sufficiently high to inhibit both
      susceptible and resistant bacteria.

PMID- 21722147
TI  - Prevalence of Escherichia coli O157:H7 on hides and faeces of ruminants at
      slaughter in two major abattoirs in Nigeria.
AB  - AIM: To determine the occurrence of Escherichia coli O157: H7 in hides and faeces
      of slaughtered ruminants in Nigeria. METHODS AND RESULTS: A total number of 320
      animals were sampled from January to December covering the wet and harmattan
      seasons. Samples were obtained from the hides and faeces of animals at slaughter.
      The ISO (ISO 16654:2001, Microbiology of food and animal feedingstuffs-
      horizontal method for the detection of Escherichia coli O157) method for
      enrichment and isolation of E. coli O157 incorporating selective enrichment using
      modified tryptone soya broth with novobiocin (mTSBn),immunomagnetic separation
      and plating on sorbitol-MacConkey agar with cefixime tellurite (CT-SMAC) was
      used. Overall cattle had a prevalence rate of 49.4% followed by sheep and goats
      with rates of 6.3% and 2.5%, respectively. There was a significant difference in
      carriage of E. coli O157 among two different cattle breeds. CONCLUSIONS: The
      prevalence of E. coli O157: H7 is substantial from two abattoirs in the country.
      The carriage and shedding of E. coli O157: H7 did not differ with season but
      differed among groups of ruminants and among breeds of cattle in a tropical
      country. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study on E. coli
      O157: H7 from abattoir operations in Nigeria. The study emphasizes the risk of E.
      coli O157: H7 along the meat chain and the need for concerted effort to limit it
      through best hygiene practices.

PMID- 21722148
TI  - Rapid genotyping assays for the identification and differentiation of Yersinia
      ruckeri biotype 2 strains.
AB  - AIMS: To establish PCR-based assays for the rapid identification and
      differentiation of each of four known biotype 2 (BT2) phenotype-causing alleles
      in Yersinia ruckeri strains currently circulating in Europe and the United
      States. METHODS AND RESULTS: Novel assays were developed relying on detection of
      mutant allele-specific changes in restriction enzyme cleavage sites within
      targeted PCR products. The developed assays were validated against isolates
      previously genotyped by DNA sequencing. CONCLUSIONS: The described methods were
      specific, rapid and simple to perform and interpret. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The developed genotyping assays provide a valuable tool for
      identification and differentiation of specific BT2 strains of Y. ruckeri. These
      assays will be critical for the design and validation of new vaccines or other
      measures meant to control BT2 strains.

PMID- 21722149
TI  - Thiopurine methyl-transferase activity and azathioprine metabolite concentrations
      do not predict clinical outcome in thiopurine-treated inflammatory bowel disease
      patients.
AB  - BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6
      thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic
      success in inflammatory bowel disease patients treated with thiopurines; however,
      this has not been implemented in clinical practice. AIM: To identify a
      therapeutic threshold value for TPMT or 6TGN concentrations, and their capability
      to predict treatment safety and efficacy. METHODS: Prospective multicentre study
      including steroid-resistant/dependent patients starting thiopurines. The TPMT
      activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites
      [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and
      6TGN/TPMT ratios] were periodically monitored during steroid tapering and after
      withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113
      patients were analysed (62% clinical response). Areas under the receiver
      operating characteristic (ROC) curve (AUC) relating clinical response and
      metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than
      0.7. The AUCs relating final response and initial TPMT activity or metabolite
      concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than
      0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight
      (7%) patients developed thiopurine-related toxicity that could not be linked to
      TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support
      determination of TPMT activity or 6TGN concentrations to predict treatment
      outcome, and no useful serum metabolites threshold value to adjust the drug's
      dose was identified.

PMID- 21722150
TI  - Central cervical lymph node metastases in papillary thyroid cancer: a systematic
      review of imaging-guided and prophylactic removal of the central compartment.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) is a common endocrine cancer and
      commonly presents with lymph node (LN) metastases. The role of surgical removal
      of the central cervical LN compartment is poorly defined. There are no
      prospective randomized controlled trials addressing the relevance to the extent
      of the initial surgical approach. DESIGN AND METHODS: A systematic review of
      studies of patients with PTC undergoing either prophylactic or therapeutic
      lymphadenectomy of the central LNs was carried out. Studies involving imaging
      modalities in the detection of LNs in PTC were also analysed. RESULTS: Twenty-one
      studies contained data on 4188 patients undergoing prophylactic or imaging-guided
      removal of the central compartment. Imaging-guided surgery retrieved cancerous
      central LNs in 346 or 30% of eligible patients, whilst prophylactic central neck
      dissection yielded histopathological proof of cancer in 898 or 26.2% of patients.
      Five imaging studies revealed data on the use of ultrasound (US) and/or
      computerized tomography (CT). The sensitivity of US and CT was poor, ranging from
      50% to 70% when accurately calculated. CONCLUSION: Metastatic central LNs are
      found in nearly half of all patients with PTC when prophylactic central lymph
      node dissection (CLND) is performed. With unreliable imaging modalities,
      prophylactic CLND should be performed on all patients with PTC.

PMID- 21722151
TI  - Adenoma granulation pattern correlates with clinical variables and effect of
      somatostatin analogue treatment in a large series of patients with acromegaly.
AB  - CONTEXT: Somatotroph adenomas have been classified into densely granulated (DG)
      and sparsely granulated (SG) tumours with a transitional, intermediate group. Gsp
      oncogenes are activating mutations in the Gsalpha subunit gene, found in
      approximately 40% of somatotroph adenomas. OBJECTIVES: To explore granulation
      pattern and presence of gsp oncogene in acromegaly with correlations to clinical
      and biochemical variables and to the effect of treatment with somatostatin
      analogues (SA), as well as to describe granulation pattern in adenomas with and
      without SA pretreatment. DESIGN/SETTINGS/PATIENTS: Seventy-eight patients with
      active acromegaly were included. Long-term SA efficacy was evaluated in 29
      patients treated preoperatively and in ten treated postoperatively. Granulation
      pattern was examined, as were immunohistochemical analyses for E-cadherin and
      SSTR2a. Protein levels of E-cadherin and SSTR2a were measured (Western blot). Gsp
      mutation analysis was available for 74 adenomas. RESULTS: DG adenomas and the
      transitional group had higher serum levels of IGF-1 per tumour volume than SG (P
      = 0.009; P = 0.005). Acute and long-term SA responses were lower in SG (P =
      0.001; P = 0.043). No correlation between gsp mutation and granulation was found,
      and no difference in granulation pattern according to preoperative SA treatment
      was demonstrated. A significant correlation between granulation and E-cadherin
      was found, where SG had lowest immunohistochemical expression, substantiated by
      protein levels, and a highly significant gradient was observed from DG, through
      the transitional group, to SG. CONCLUSIONS: Densely granulated adenomas were
      highly responsive to somatostatin analogues in contrast to SG adenomas. The
      transitional group behaved clinically more like DG adenomas. However, based on E
      cadherin, a marker of dedifferentiation, the transitional group seemed to be a
      true intermediate.

PMID- 21722152
TI  - Beyond PTH: assessing vitamin D status during early pregnancy.

PMID- 21722153
TI  - Identification of a novel mutation in the exon 2 splice donor site of the
      POU1F1/PIT-1 gene in Japanese identical twins with mild combined pituitary
      hormone deficiency.
AB  - CONTEXT: To date, approximately 35 different POU1F1 mutations have been described
      in patients with familial and sporadic combined pituitary hormone deficiency
      (CPHD) from different ethnic backgrounds. The majority are missense mutations
      clustered within the conserved POU-specific and POU-homeo domains, encoded by
      exons 4 and 6, respectively. OBJECTIVES: This study aimed to identify the
      molecular basis and clinical characteristics of a Japanese CPHD family with a
      novel POU1F1 mutation. DESIGN: The POU1F1 gene was sequenced in identical twin
      brothers with mild CPHD. The mutation identified was also evaluated in family
      members as well as 188 Japanese controls and then examined in functional studies.
      RESULTS: A novel heterozygous splice site mutation (Ex2 + 1G>T; c.214 + 1G>T) was
      detected. This mutation was also present in their undiagnosed mother, but not in
      any of the controls. In vitro splicing studies suggested this mutation to result
      in an in-frame skipping of exon 2, thus producing an internally deleted protein
      lacking most of the R2 transactivation subdomain (TAD-R2). Heterologous
      expression studies of the mutated POU1F1 protein showed only modest reductions in
      its transactivation activities in HEK293T cells, while acting as a dominant
      negative inhibitor of the endogenous activities of POU1F1 in pituitary GH3 cells.
      CONCLUSIONS: This is the first report of a mutation at the exon 2 donor splice
      site of POU1F1, affecting TAD-R2. The addition of this mutation to the growing
      list of pathological POU1F1 mutations may provide deeper insights into clinical
      heterogeneity in the expressions of individual mutations and a better
      understanding of the structure-function relationships of POU1F1.

PMID- 21722154
TI  - Impact of dental implant length on early failure rates: a meta-analysis of
      observational studies.
AB  - AIM: To test the null hypothesis of no difference in failure rates of short
      (minimum length: 7 mm) and longer dental implants (>= 10 mm), a meta-analysis was
      performed on prospective observational trials. MATERIALS AND METHODS: A
      systematic electronic and hand search was performed to identify eligible studies.
      Having additional data supplied by the authors, 54 publications were included
      (19,083 implants). RESULTS: In case of mandibular implants, the null hypothesis
      of no impact of reduced implant length on failure within the first year of
      prosthetic loading could not be rejected. A significant impact of implant length
      could be substantiated for short machined implants in the anterior [odds ratio
      (OR) 5.4] and posterior maxilla (OR 3.4), while short rough-surfaced implants
      demonstrated increased failure rates in the anterior maxillary sites. No
      influence of implant diameter and denture type on the failure rate of short
      implants could be revealed. CONCLUSION: In areas of reduced alveolar bone height
      the use of short dental implants may reduce the need for invasive bone
      augmentation procedures.

PMID- 21722155
TI  - The relationship between periodontitis and metabolic syndrome among a Korean
      nationally representative sample of adults.
AB  - AIMS: The aim of this study was to examine whether metabolic syndrome (MS) is
      associated with periodontitis in a representative sample of Korean adults, who
      were involved in the Fourth Korea National Health and Nutrition Examination
      Survey (KNHANES). MATERIALS AND METHODS: A total of 7178 subjects over the age of
      19 years who participated in KNHANES were examined. MS was defined as the
      definition proposed by the National Cholesterol Education Program Adult Treatment
      Panel III and the abdominal obesity cut-off line based on Korean Society for the
      Study of Obesity. The periodontal status was assessed by the Community
      Periodontal Index. Multivariate logistic regression analysis was carried out
      adjusting for the sociodemographics, oral health behaviours and status, and
      health behaviour. All analyses considered a complex sampling design, and
      multivariate analysis was also performed in the subgroups (age, gender, current
      smoking status). RESULTS: Multivariate logistic regression analysis revealed
      significant associations between MS and periodontitis. After adjusting for all
      covariates, the adjusted odds ratio (OR) of periodontitis (community periodontal
      index >= 3) was 1.55 (1.32-1.83) for MS. In subgroup analysis, periodontitis is
      associated with MS in subjects over age 40 and the adjusted ORs were higher in
      females and in the smoker group than in males and in non-smokers. CONCLUSIONS: MS
      is associated with periodontitis.

PMID- 21722156
TI  - Identification and functional validation of CDH11, PCSK6 and SH3GL3 as novel
      glioma invasion-associated candidate genes.
AB  - AIMS: The molecular mechanisms underlying the infiltrative growth of
      glioblastomas, the most common primary tumours of the central nervous system in
      adults, are still poorly understood. We aimed to identify and functionally
      validate novel glioma invasion-associated candidate genes. METHODS: Microarray
      based expression analysis was applied to identify differentially expressed genes
      in microdissected infiltrating glioma cells in vivo. Promising candidate genes
      were selected by the invasion-associated gene ontology terms cell adhesion,
      endocytosis, extracellular matrix and cell migration and validated in vitro by
      invasion assays and in situ by immunohistochemistry. RESULTS: We identified 180
      up-regulated and 61 down-regulated genes (fold change: >= 2; P < 0.01) in the
      infiltration zone relative to more central cell-rich tumour areas of malignant
      astrocytic gliomas (n = 11). Twenty-seven of these genes matched to invasion
      related gene ontology terms. From these, we confirmed the genes encoding cadherin
      11 (CDH11), proprotein convertase subtilisin/kexin type 6 (PCSK6) and SH3-domain
      GRB2-like 3 (SH3GL3) as novel glioma invasion-associated candidate genes, with
      knockdown of PCSK6 and SH3GL3 inhibiting glioma cell invasion, while inhibition
      of CDH11 promoted glioma cell invasion in vitro. Immunohistochemistry on
      glioblastoma tissue sections revealed expression of CDH11 and PCSK6 protein in
      glioma cells of more central, cell-rich tumour areas, with only weak or absent
      CDH11 immunoreactivity but consistent PCSK6 staining in infiltrating glioma
      cells. CONCLUSION: Using molecular profiling of microdissected primary tumour
      tissue specimens followed by functional in vitro analysis, we identified and
      validated CDH11, PCSK6 and SH3GL3 as novel glioma invasion-associated candidate
      genes that likely contribute to the invasive phenotype of malignant gliomas.

PMID- 21722157
TI  - An examination of how adolescent-caregiver dyad illness representations relate to
      adolescents' reported diabetes self-management.
AB  - BACKGROUND: Adolescence is a period associated with poor glycaemic control. The
      key developmental concerns of young people are in conflict with the requirements
      of diabetes self-management. This study explores the relative influence of
      adolescents' and caregivers' illness representations and how any
      difference/similarity in their representations may be related to adolescents'
      diabetes self-management. METHODS: Fifty-five adolescents between 12 and 16 years
      of age were asked to complete the Diabetes Illness Representation Questionnaire
      and Summary of Diabetes Self-Care Activities Questionnaire. Their primary
      caregivers were asked to complete a caregivers' version of the Diabetes Illness
      Representation Questionnaire. RESULTS: Caregivers believed diabetes to be more
      chronic, to have a more negative impact, pose more of a threat to adolescents'
      health and believed more strongly in the effectiveness of treatment than did
      adolescents. Caregivers' representations about the impact of diabetes and the
      ability of treatment to prevent future complications were related to adolescents'
      dietary self-management. CONCLUSIONS: This study emphasizes the important role of
      significant others illness representations in adolescent self-management of
      diabetes.

PMID- 21722158
TI  - An examination of information-processing skills among inhalant-using adolescents.
AB  - BACKGROUND: This study investigates the association between inhalant use and
      information processing (IP) in adjudicated polysubstance users. Polysubstance
      users who used inhalants (n= 158) were compared with polysubstance users who did
      not use inhalants (n= 303). Hispanic Americans comprised 72% of the participants;
      European Americans, African Americans and Asian Americans comprised 28% of the
      participants. METHOD:   Standardized intelligence and achievement tests were used
      to assess information-processing constructs of working memory and processing
      speed. Psychosocial and substance abuse standardized surveys were used to assess
      drug use severity and psychosocial problems associated with substance use.
      RESULTS: Polysubstance users who used inhalants (PSI users) were younger, used
      more drugs more frequently and had more psychiatric admissions than non-inhalant
      polysubstance users (PSO users). Statistical analysis also shows that PSI users
      performed worse on measures of IP selected tests in comparison with the PSO
      users. CONCLUSION: Inhalant users begin abusing substances at a younger age and
      suffer from more verbal and non-verbal processing, behavioural, language and
      memory problems than non-inhalant users.

PMID- 21722159
TI  - Accidental injuries are more common in children with attention deficit
      hyperactivity disorder compared with their non-affected siblings.
AB  - BACKGROUND: Accidental injuries are a leading cause of paediatric morbidity and
      mortality. We hypothesized that attention deficit hyperactivity disorder (ADHD),
      a common childhood disorder characterized by behaviours such as hyperactivity and
      impulsivity, is a risk factor for accidental injuries. Previous retrospective
      studies suggested that children with ADHD have an increased injury rate, but
      controlled prospective studies are lacking. METHODS: We conducted a prospective
      case-control study of 29 school-aged children with ADHD and their same-sex,
      similarly aged, non-ADHD-affected siblings. All diagnoses were made by a
      paediatric neurologist according to DSM-IV criteria and the children and their
      parents underwent a structured psychiatric interview and a battery of
      complementary assessments including: Child Behavior Checklist (CBCL), ADHD Rating
      scale and Developmental Coordination Disorder Questionnaire (DCDQ). The parents
      were contacted by telephone every 3 months during a 9-month follow-up period and
      all injuries requiring medical attention were recorded. Incidence of injuries was
      compared between the pairs of siblings. RESULTS: During the follow-up period, a
      total of 13 injuries in 13 children with ADHD were reported, compared with six
      injuries in six children from the control group (Z=-2.11, P < 0.05). ADHD
      severity and subtype, CBCL, DCDQ and IQ scores were not predictive of injury
      risk. CONCLUSIONS: School-aged children with ADHD are at higher risk of
      accidental injuries than their non-ADHD siblings, regardless of ADHD subtype, co
      morbid psychiatric conditions, developmental co-ordination problems and
      environmental/familial conditions. Awareness and adequate education of parents
      and caregivers of children with ADHD concerning the increased injury risks are
      thus warranted.

PMID- 21722160
TI  - How do children with a chronic or long-term illness perceive their school re
      entry after a period of homebound instruction?
AB  - BACKGROUND: A considerable number of children are confronted with a chronic or
      long-term illness in their lives. For these children, absenteeism is problematic,
      because education plays a major role in stimulating their cognitive development
      and in promoting a sense of normalcy and psychosocial well-being. In the
      literature, a great deal of attention has been paid to school reintegration
      programmes, which try to counter the barriers that these children may face when
      they return to school. Another way of surmounting these barriers is through the
      use of homebound instruction, in which the educational process for the child is
      continued during the period of absence. Despite the growing awareness of the
      necessity of education for these children, there is still little empirical
      research available addressing programmes that facilitate school re-entry.
      METHODS: The major goal of this study is to investigate how parents and their
      children with a chronic or long-term illness perceive school re-entry after a
      period of homebound instruction, by using a descriptive-explorative, multi
      informant research design. Participants were 60 children and their parents who
      filled in a self-constructed questionnaire. RESULTS: Both parents and children
      perceived the period of homebound instruction, as well as their school re-entry,
      predominantly positively. Most of the children stated that they had been able to
      keep up with their subjects, and that they had good contact with their peers when
      they returned to school. According to parents, homebound instruction made a
      positive contribution to the school re-entry of their child. CONCLUSIONS: The
      current study is one of the first to explore the school re-entry of children with
      a chronic or long-term illness. According to both parents and children, the
      school re-entry process passed off positively. However, more research is needed
      with regard to the quality of education and the programmes aimed at facilitating
      school re-entry.

PMID- 21722161
TI  - Cardiac ischaemic stress: cardiomyocyte Ca2+, sex and sex steroids.
AB  - 1. Important sex differences exist in ischaemic heart disease. Oestrogen has been
      conventionally regarded as providing a cardioprotective benefit and testosterone
      frequently perceived to exert a deleterious effect. However, there is
      accumulating evidence that argues against this simple dichotomy, suggesting that
      the influence of oestrogen and testosterone conferring benefit or detriment may
      be context specific. 2. Cardiomyocyte calcium (Ca(2+)) loading is recognized to
      be a major factor in acute ischaemia-reperfusion pathology, promoting cell death,
      contractile dysfunction and arrhythmogenic activity. Ca(2+)/calmodulin-dependent
      kinase II (CaMKII) is a mediator of many of the cardiomyocyte Ca(2+)-related
      pathologies in ischaemia-reperfusion. Cardiomyocyte Ca(2+)-handling processes
      have been shown to be modulated by the actions of oestrogen and testosterone. A
      role for these sex steroids in influencing CaMKII activation is argued. 3.
      Although many experimental studies of oestrogen manipulation can identify a
      cardioprotective role for this sex steroid, there are also numerous reports that
      fail to demonstrate sex differences in postischaemic recovery. Experimental
      studies report that testosterone can be protective in ischaemia-reperfusion in
      males and females in some settings. 4. Further studies of sex steroid influence
      in the ischaemic heart will allow the development of therapeutic interventions
      that are specifically targeted for male and female hearts.

PMID- 21722162
TI  - Advances in stroke care and research in 2010.
AB  - 1. There have been many advances in stroke research and care over the past year.
      The aim of the present review is to highlight the significant advances that are
      likely to have considerable impact on the direction of future investigations and
      models of clinical practice. 2. In terms of the acute treatment of stroke, there
      is now Level I evidence for the use of thrombolysis in the treatment of ischaemic
      stroke. The results of clinical trials suggest potential new treatments for
      stroke of inherited origin, whereas other potential treatments have been
      suggested following the identification of a novel mechanism of emboli clearance
      by extravasation. Clinical guidelines have also been updated, with tight blood
      pressure control advocated in cases of acute intracerebral haemorrhage. 3. In
      terms of stroke prevention, new information has been added to the long-standing
      debate regarding the value of carotid stenosis management: the predictive value
      of asymptomatic carotid emboli may enable the identification of individuals at
      high risk of stroke. Furthermore, the identification of novel risk factors for
      stroke opens up new avenues for stroke prevention. 4. Robot-assisted therapy has
      heralded a new era in stroke rehabilitation and the 'Get With The Guidelines'
      programme has set a milestone in the quality control of stroke care. 5.
      Undoubtedly these advances will have a marked impact on future research and
      clinical practice.

PMID- 21722163
TI  - Effects of a maternal diet supplemented with chocolate and fructose beverage
      during gestation and lactation on rat dams and their offspring.
AB  - 1. Consumption of a high-fat and high-energy diet during pregnancy leads to a
      risk of long-term consequences on fetal development, as well as on the postnatal
      health of offspring. To investigate the effects of such a diet on fetal
      programming, we established a high-energy intake pregnant rat model using
      chocolate and fructose beverage as supplements to a normal chow diet. 2. Pregnant
      Sprague-Dawley rats were assigned to either chow (control) or a diet supplemented
      with chocolate and fructose beverage throughout gestation and lactation. The male
      F(1) pups received normal chow diet after weaning. Physiological or pathological
      changes in dams and pups (e.g. glucose and lipid metabolism) were evaluated. 3.
      The results showed that dams offered the high-fat (mainly from chocolate) and
      high-calorie diet during gestation consumed more energy and gained more weight
      than chow-fed dams. Over-consumption of chocolate reduced chow intake in dams,
      leading to low maternal protein supply. As a result, pups from these dams
      exhibited reduced birth weight that lasted until adulthood. The high-energy diet
      during lactation led to increased total body fat, as well as impaired liver
      function, in offspring; thus, the lactational diet is suggested to be a stronger
      determinant of offspring fat metabolism than gestational diet. 4. The results of
      the study suggest that over-supply of carbohydrates, such as chocolate and
      fructose, either during gestation or lactation has a negative impact on the well
      being of offspring.

PMID- 21722164
TI  - Non-direct patient care factors influencing nursing workload: a review of the
      literature.
AB  - AIMS: The aim of this paper was to detect which non-direct patient care factors
      are related to nursing workload in acute hospital nursing care and to develop a
      conceptual model to describe the relationship between the non-direct patient care
      factors and nursing workload. BACKGROUND: Since the 1930s, efforts to measure
      nursing workload have been undertaken. Still, it remains unclear which of the non
      direct patient care elements are essential to the nursing workload. DATA SOURCES:
      PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature,
      Engineering Village 2, Elin and the British Nursing Index were searched from 1970
      up to July 2009. REVIEW METHODS: Studies were included in this integrative review
      if they described factors that are related to nursing workload or if they
      presented models that explored the association between potential factors,
      excluding the factors related to direct patient care. RESULTS: Thirty
      publications were included. The influencing variables were classified in five
      categories based on their level of impact: the hospital and ward, nursing team,
      individual nurse, patient and family and meta-characteristics. The variables were
      also classified, based on their cause-effect relationship. Some factors have a
      direct impact on the patient-nurse relationship, while others have an effect on
      the work fluency or on the subjective perception of the nursing workload. A
      conceptual model was built, based on the interaction between both classifications
      and derived from the systems theory. CONCLUSIONS: Nursing workload has a multi
      causal aetiology. The influencing factors from this review can be integrated in a
      workload measurement tool.

PMID- 21722165
TI  - Psychometric testing of the abbreviated Clinical Learning Environment Inventory
      (CLEI-19).
AB  - AIM: This paper is a report of a test of the psychometric properties of a 19-item
      version of the Clinical Learning Environment Inventory. BACKGROUND: Although the
      clinical learning environment provides the 'real-life' context essential for
      preparing nursing students for their professional role, the quality of student
      learning is influenced by the quality of the clinical placement. METHODS: Nursing
      students completed an abbreviated (19-item) form of the Clinical Learning
      Environment Inventory to rate their perception of the clinical learning
      environment. Descriptive statistics, principal component analysis, discriminant
      validity and Cronbach's alpha reliabilities were computed. RESULTS: Between March
      and December 2009, 231 online surveys were submitted. The mean age of
      participants was 30.3 years (sd: 10.4) and 87% were female. All 19 items loaded
      on two factors, 'Clinical Facilitator Support of Learning' and 'Satisfaction with
      Clinical Placement', with factor loadings above the 0.4 threshold. Cronbach's
      alpha coefficient was 0.93 for the total Clinical Learning Environment Inventory
      19, with subscales ranging from 0.92 to 0.94. Multiple regression uncovered that
      participants who engaged in health-related paid work were independently and
      significantly more positive on the 'Clinical Facilitator Support of Learning'
      subscale, whereas those who worked >16 hours a week, or allocated the afternoon
      shift were independently and significantly more negative on the 'Satisfaction
      with Clinical Placement' subscale. CONCLUSION: Providing an effective and
      productive clinical experience is vital in preparing nursing students to become
      competent clinicians. The Clinical Learning Environment Inventory-19 offers a
      useful measure to explore nursing students' satisfaction with two aspects of this
      clinical experience--clinical facilitator support of learning and the clinical
      learning environment.

PMID- 21722166
TI  - A structural model of the bio-psycho-socio-spiritual factors influencing the
      development towards gerotranscendence in a sample of institutionalized elders.
AB  - AIMS: This paper is a report of a study to determine the bio-psycho-socio
      spiritual factors influencing the development towards gerotranscendence in
      institutionalized older people. Physical ability, depressive symptoms, social
      network support, meaning of life and life satisfaction were examined through a
      structured equation modelling approach. BACKGROUND: Older people's pursuit of
      gerotranscendence is believed to facilitate successful ageing and late-life
      growth. Although a few Scandinavian studies have identified the relationship
      between psychosocial factors and the development of gerotranscendence, there is
      little trans-cultural study of the model, which limits the ability of the
      gerotranscendence theory to be applied worldwide. METHODS: Cognitively intact
      older residents (N = 195) from six long-term care facilities in southern Taiwan
      participated in a structured interview using the Gerotranscendence scale,
      Barthel's Index, the Geriatric Depression Scale short form, the Inventory of
      Socially supportive Behaviour, the Life Meaning scale, and the Life Satisfaction
      scale. Data were collected over a 6-month period in 2008. RESULTS: The model-fit
      indexes of the final model (chi2)  = 32.08, d.f. = 14, P = 0.004; CMIN/d.f. =
      2.29; GFI = 0.97, AGFI = 0.89, TLI = 0.94, NFI = 0.96) exceeded acceptable levels
      except for chi2 . In the final model, social support, life satisfaction and
      meaning of life had direct effects on gerotranscendence (standardized regression
      weight 0.54, 0.43, and 0.76). CONCLUSION: The gerotranscendence model of healthy
      ageing is congruent in the Taiwanese population. Findings of this study can guide
      nursing and other health professionals in planning implementation of best
      practice in older people's care.

PMID- 21722167
TI  - An empowerment framework for nursing leadership development: supporting evidence.
AB  - AIM: This article is a report on a descriptive study of nurse leaders'
      perspectives of the outcomes of a formal leadership programme. BACKGROUND:
      Effective nurse leaders are necessary to address complex issues associated with
      healthcare systems reforms. Little is known about the types of leadership
      development programmes that most effectively prepare nurse leaders for healthcare
      challenges. When nurse leaders use structural and psychological empowerment
      strategies, the results are safer work environments and better nurse outcomes.
      The leadership development programme associated with this study is based on a
      unifying theoretical empowerment framework to empower nurse leaders and enable
      them to empower others. METHODS: Twenty seven front-line and mid-level nurse
      leaders with variable years of experience were interviewed for 1 year after
      participating in a formal leadership development programme. Data were gathered in
      2008-2009 from four programme cohorts. Four researchers independently developed
      code categories and themes using qualitative content analysis. RESULTS: Evidence
      of leadership development programme empowerment included nurse leader reports of
      increased self-confidence with respect to carrying out their roles and
      responsibilities; positive changes in their leadership styles; and perceptions of
      staff recognition of positive stylistic changes. Regardless of years of
      experience, mid-level leaders had a broader appreciation of practice environment
      issues than front-line leaders. Time for reflection was valuable to all
      participants, and front-line leaders, in particular, appreciated the time to
      discuss nurse-specific issues with their colleagues. CONCLUSION: This study
      provides evidence that a theoretical empowerment framework and strategies can
      empower nurse leaders, potentially resulting in staff empowerment.

PMID- 21722168
TI  - Effectiveness of heparin solution versus normal saline in maintaining patency of
      intravenous locks in neonates: a double blind randomized controlled study.
AB  - AIM: The aim of this study was to evaluate the effect of heparin versus saline as
      flush solution for maintaining patency in peripheral intravenous locks in
      neonates and to investigate whether other variables influence the longevity of
      intravenous locks. BACKGROUND: Heparin is usually used as a regular flush
      solution to prevent occlusion of peripheral intravenous locks in neonates. There
      is no clear recommendation using heparin or saline flushing peripheral
      intravenous locks in neonates. The disadvantage of heparin cannot be ignored,
      especially in this patient group. METHODS: In a double blind prospective
      randomized study, neonates (gestational age >27 weeks) with intravenous locks
      were randomly assigned to receive heparin or saline as a flush solution in a 21
      month period (2002-2004). The main outcome was the duration of patency. RESULTS:
      Eighty-eight neonates were included. No statistically significant difference was
      found in patency of peripheral intravenous locks flushed with 0.7 mL heparin (10
      units/mL) (N = 42, median 56 hours) or 0.7 mL saline (N = 46, median 61 hours).
      When the analysis was confined to removed locks because of non-elective events,
      no statistically significant difference was found in duration of patency (P =
      0.27). CONCLUSION: As no difference in patency could be established, using saline
      as a flush solution is preferable to heparin in peripheral intravenous locks in
      neonates, given the greater likelihood of complications associated with heparin.
      Although these data are more than 5 years old, the relevance of the outcome is
      still important for the clinical practice because of the potential adverse
      effects of heparin in these vulnerable infants.

PMID- 21722169
TI  - A systematic model to compare nurses' optimal and actual competencies in the
      clinical setting.
AB  - AIM: This paper is a report of a study to develop a model to compare nurses'
      optimal and actual competencies in the clinical setting. BACKGROUND:   Although
      future challenge is to focus the developmental and educational targets in health
      care, limited information is available on methods for how to predict optimal
      competencies. METHOD: A multidisciplinary group of 24 experts on perioperative
      care were recruited to this study. They anticipated the effects of future
      challenges on perioperative care and specified the level of optimal competencies
      by using the Nurse Competence Scale before and after group discussions. The
      expert group consensus discussions were held to achieve the highest possible
      agreement on the overall level of optimal competencies. Registered Nurses (n =
      87) and their nurse managers from five different units conducted assessments of
      the actual level of nurse competence with the Nurse Competence Scale instrument.
      Data were collected in 2006-2007. RESULTS: Group consensus discussions solidified
      experts' anticipations about the optimal competence level. This optimal
      competence level was significantly higher than the nurses' self-reported actual
      or nurse managers' assessed level of actual competence. The study revealed some
      competence items that were seen as key challenges for future education of
      professional nursing practice. CONCLUSION: It is important that the
      multidisciplinary experts in a particular care context develop a share
      understanding of the future competency requirements of patient care. Combining
      optimal competence profiles to systematic competence assessments contribute to
      targeted continual learning and educational interventions.

PMID- 21722170
TI  - Job satisfaction, occupational commitment and intent to stay among Chinese
      nurses: a cross-sectional questionnaire survey.
AB  - AIM: This study was designed to identify the level of nurses' job satisfaction,
      occupational commitment and intent to stay among mainland Chinese nurses, to
      explore the relationship among them. BACKGROUND:   Little is known about the
      magnitude of Chinese nurses' intent to stay. Understanding the association among
      demographic characteristics and job satisfaction, occupational commitment and
      intent to stay among Chinese nurses is most important in a time of nurse
      shortages. Methods.  A descriptive correlation design was used to examine the
      relationship among variables related to intent to stay. Data were collected by a
      self-administered survey questionnaire from 560 nurses working in four large
      hospital facilities in Shanghai in 2009. RESULTS: The mean scores for nurses' job
      satisfaction, occupational commitment and intent to stay were 3.25(0.48),
      3.11(0.40) and 3.56(0.65), respectively. Job satisfaction and occupational
      commitment were significantly related to intent to stay. A statistically
      significant positive correlation was found between occupational commitment and
      job satisfaction. Age and job position were significantly related to job
      satisfaction, occupational commitment and intent to stay. CONCLUSION: Levels of
      job satisfaction, occupational commitment and intent to stay reported by nurses
      in this study can be improved. Suggested strategies for improvement are:
      increasing salaries, decreasing workloads, modifying task structure, cultivating
      work passion and creating more professional opportunity for nurses' personal
      growth development and promotion. Enhancing nurses' job satisfaction and
      occupational commitment are vital to improve nurses' intent to stay and for
      strategies to address the nursing shortage.

PMID- 21722171
TI  - A comparison of the hand hygiene knowledge, beliefs and practices of Italian
      nursing and medical students.
AB  - AIM: This paper reports a study examining the hand hygiene knowledge, beliefs and
      practices of Italian nursing and medical students with the aim of informing
      undergraduate curricula. BACKGROUND: In comparison with registered nurses,
      physician status is a risk factor for non-compliance with hand hygiene
      guidelines. Little research has been conducted to determine if differences
      between the professions in relation to hand hygiene are apparent at the
      undergraduate level. Cross-disciplinary studies that may provide an insight into
      this topic are lacking. METHODS: A questionnaire was administered to a
      convenience sample of 117 nursing and 119 medical students in a large university
      in Rome, Italy, to determine their hand hygiene knowledge, beliefs and practices.
      The data were collected in 2007-2008. RESULTS: Nursing students' hand hygiene
      knowledge (F = 9.03(1,230); P = 0.003), percentage compliance (Z = 6.197; P <
      0.001) and self-reported hand hygiene practices (F = 34.54(1,230); P < 0.001)
      were significantly higher than that of medical students. There were no
      statistically significant differences between hand hygiene beliefs. Mean scores
      on the knowledge questions were low for both groups, reflecting primarily a
      knowledge deficit in relation to the use of alcohol-based hand rubs to
      decontaminate hands in the healthcare setting. CONCLUSION: Statistically
      significant disciplinary differences in hand hygiene knowledge and self-reported
      practices were apparent among undergraduate Italian healthcare students. Further
      research is needed to determine the causative factors. The overall low scores on
      the knowledge items indicate that these students require further education on
      hand hygiene, particularly in relation to the use of alcohol-based hand rubs.

PMID- 21722172
TI  - Induction of trap formation in nematode-trapping fungi by a bacterium.
AB  - Three soil bacterial strains were identified as Chryseobacterium sp. TFB on the
      basis of their 16S rRNA gene sequences. Conidia of Arthrobotrys oligospora
      produced a few mycelial traps (MT) and conidial traps (CT) when cultured with
      bacterial cells that they did not produce when cultured with a bacterial cell
      free culture filtrate. However, co-culture of A. oligospora with bacterial cells
      and bacteria-free filtrate simultaneously induced MT and CT in large amounts.
      With the increased concentration of bacteria-free filtrate, the number of typical
      CT increased, but conidial germination was progressively inhibited. Scanning
      electron microscopy of A. oligospora co-cultured with bacteria revealed that
      bacterial attachment to hyphae was a prerequisite to trap formation and that
      bacteria-free filtrate facilitated bacterial attachments to hyphae. The results
      that the addition of nutrients in co-culture medium decreased the number of traps
      suggest that this type of trap formation may be favoured at a low nutrient
      status. Eight fungi tested were able to form MT and CT when co-cultured with
      bacterial cells and bacteria-free culture filtrate, but the abilities varied
      among species. This study provides novel evidence that under laboratory
      conditions, soil bacteria attaching to hyphae could induce traps in nematode
      trapping fungi.

PMID- 21722173
TI  - Increasing prevalence of coeliac disease in Denmark: a linkage study combining
      national registries.
AB  - AIM: To determine the prevalence and incidence of diagnosed coeliac disease (CD)
      in Danish children and adolescents and to describe trends over time. METHODS: All
      children with a CD diagnosis registered in the Danish National Patient Registry
      (DNPR) were included in the study. Data were validated by combining this
      information with registrations of small-bowel biopsies in the National Registry
      of Pathology (NRP) and with a selected sample of hospital records. RESULTS: Data
      were obtained from 1996 to 2010. The prevalence of CD registered in DNPR
      increased from 43.2 [95% CI 39.3-47.1] to 83.6 [95% CI 78.4-88.7] per 100,000,
      and the incidence increased from 2.8 [95% CI 1.9-3.9] to 10.0 [95% CI 8.4-12.0]
      per 100,000; 56% of the children had at least one biopsy compatible with CD
      registered in NRP. The incidence of biopsy-verified CD increased from 0.8 [95% CI
      0.3-1.4] to 6.9 [95% CI 5.4-8.4] per 100,000. The mean age at diagnosis increased
      from 5.1 [95% CI 3.5-6.6] to 8.1 [95% CI 7.2-9.0] years of age. The proportion of
      children with associated diseases did not change over time. CONCLUSION: The
      prevalence of diagnosed CD in Danish children and adolescents has increased over
      the last 15 years.

PMID- 21722174
TI  - Amplitude-integrated EEG differences in premature infants with and without
      bronchopulmonary dysplasia: a cross-sectional study.
AB  - AIM: To evaluate differences in amplitude-integrated electroencephalogram (aEEG)
      recordings of infants with and without bronchopulmonary dysplasia (BPD). METHODS:
      This is a cross-sectional study of infants <=27 weeks at birth who did (n = 17)
      or did not develop BPD (n = 17). aEEG tracings were recorded at 36(0) -36(6)
      weeks post-menstrual age for 6 h using the BrainZ BRM3 monitor. A cross-cerebral
      channel was evaluated using offline software Analyze (BrainZ). RESULTS: Infants
      with BPD had lower gestational age and higher male predominance (25 +/- 1 weeks,
      70%) compared with non-BPD infants (26 +/- 1 weeks, 30%, all p <= 0.03), but
      similar birth weight (704 +/- 195 vs. 796 +/- 167 g, p = 0.1). During active
      sleep, infants with BPD had wider span voltage (p = 0.03), higher lower border
      voltage (p < 0.03), as well as less periods of quiet sleep per hour (p < 0.01)
      compared with non-BPD infants. These differences persisted after adjustment for
      covariates. CONCLUSION: Infants with BPD have small but significant differences
      in their aEEG tracings compared with infants without BPD at 36 weeks. Further
      study of infants with BPD using aEEG appears justified to determine whether aEEG
      variables correlate with neurodevelopmental outcome.

PMID- 21722175
TI  - Regional, socioeconomic and urban-rural disparities in child and adolescent
      obesity in China: a multilevel analysis.
AB  - AIM: To study socio-demographic patterns of obesity in Chinese children and
      adolescents. METHODS: Data came from the 2005 cycle of the Chinese National
      Survey on Student's Constitution and Health. In all, 231,326 subjects aged 7-18
      years, distributed across 622 schools and 30 provinces, were analysed. Multilevel
      modelling was used to estimate variations at individual, school area and province
      levels. RESULTS: The prevalence of obesity varied enormously across different
      areas. Young people living in high socioeconomic and urban areas had higher body
      mass index (BMI) and higher odds of overweight and obesity than those living in
      lower socioeconomic and rural areas. Subjects living in provinces with a higher
      standard of living, as indicated by less perinatal mortality, lower Engel
      coefficient, and higher personal expenditure on health had higher BMI and higher
      odds of overweight and obesity than those living in less affluent provinces. An
      interaction between gender and urbanicity revealed that boys in urban areas were
      especially prone to obesity. CONCLUSION: In contrast to most present-day high
      income countries, obesity among young people in China is associated with
      affluence and urban residence. Intervention and strategy for obesity prevention
      should be targeting high socioeconomic families in urban areas, perhaps with
      particular focus on boys.

PMID- 21722176
TI  - Association of 8q24.21 loci with the risk of colorectal cancer: a systematic
      review and meta-analysis.
AB  - BACKGROUND AND AIM: Recent genome-wide association studies of colorectal cancer
      (CRC) have identified rs6983267 and trs10505477 polymorphisms as key loci in the
      8q24 region to be associated with CRC. In the present study, we performed a meta
      analysis to determine whether these loci are risk factors for susceptibility to
      CRC. METHODS: We meta-analyzed the 22 included studies (47 003 cases and 45 754
      controls) that evaluated the association of rs6983267 and trs10505477 with CRC
      under alternative genetic models. RESULTS: A meta-analysis of the pooled data
      showed allelic and genotypic association of the rs6983267 polymorphism with CRC
      risk in Asians, Europeans, and European-Americans. A subanalysis of the US
      studies showed negative results in the studies with non-identified ethnicity of
      the patients. A meta-analysis of included studies of rs10505477 polymorphisms
      identified allelic and genotypic associations with CRC risk in the US patients. A
      further meta-analysis of the US studies demonstrated positive results in the
      studies with non-identified ethnicity of the samples. CONCLUSION: Our data
      suggested that the rs6983267 G > T polymorphism is a risk factor for CRC in
      Asians, Europeans, and Americans with European ancestry.

PMID- 21722177
TI  - Detection of single-nucleotide polymorphisms in the intron 9 region of the
      nucleotide oligomerization domain-1 gene in ulcerative colitis patients of North
      India.
AB  - BACKGROUND AND AIM: The nucleotide-binding oligomerization domain-1 (NOD1) gene
      encodes a pattern recognition receptor that senses pathogens. NOD1/caspase
      recruitment domain (CARD4) signaling leads to the activation of nuclear factor
      kB, and plays an important role in innate immunity. Certain polymorphisms and
      mutations in NOD1/CARD4 might result in a dysfunctional innate immune response
      during bacterial recognition, which might have direct implications in
      inflammatory bowel disease (IBD) pathogenesis. METHODS: We carried out a systemic
      analysis for the presence of polymorphic variants in the intron 9 region of the
      leucine-rich repeat (LRR) domain encompassing the exon-intron boundaries of the
      NOD1 gene. To detect unknown single-nucleotide polymorphisms, we used the
      denaturing high-performance liquid chromatography (DHPLC) screening technique and
      validated our data by restriction fragment length polymorphism and direct
      sequencing. RESULT: Genotype and allele frequencies showed significant
      differences in their distribution. The mutations discriminating alleles in the
      intron 9 region of the LRR domain of the NOD1 gene were correctly predicted by
      DHPLC technique and statistically verified in IBD and non-IBD individuals. Of the
      seven mutations detected, only four showed a significant association with disease
      activity. Mutations detected earlier in the exon 6 region of NOD1 were also used
      for the haplotype analysis. The GTTG haplotype was found to be significantly
      overrepresented in ulcerative colitis (UC) patients, as compared to the controls
      (P = 3.3726E(-6) ). CONCLUSION: Our study has revealed a polymorphism association
      in the LRR domain of the NOD1 gene with the severity of UC disease. This might be
      due to disruption of the LRR region critical for NOD1-mediated bacterial sensing.
      A gene-wide, haplotype-based approach shows that GTTG haplotype carriers are
      overrepresented in UC patients, and that could increase the risk of the disease.

PMID- 21722178
TI  - New technique for safer endoscopic submucosal dissection using the duodenal
      balloon occlusion method.
AB  - BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) enables complete,
      collective removal of gastrointestinal (GI) malignant tumors, but requires a long
      operation time. Air insufflated during ESD is distributed throughout the entire
      GI tract, and thus causes an enlarged feeling of the abdomen. We aimed to reduce
      the incidence of an enlarged feeling of the abdomen by wedging a balloon in the
      bulbus duodeni to reduce air flow into the lower parts of the GI tract. METHODS:
      Sixteen patients who were approved by the institutional ethics committee and
      provided consent to participate in this single-center, prospective study were
      divided into two groups using a sealed-envelope randomization method: ESD with a
      balloon wedged in the bulbus duodeni (the balloon [+] group) or conventional ESD
      with no balloon (the balloon [-] group). Total air volume in the entire GI tract
      and its change before and after ESD were measured objectively by 3-D computed
      tomography. RESULTS: In the balloon (+) group, the mean intestinal gas volume (+/
      standard deviation) was 274.3 +/- 142.0 mL before ESD, and 352.5 +/- 183.2 mL
      after, with a mean change of 78.1 +/- 139.7 mL. The increase in intestinal gas
      volume was well controlled. No postoperative complications, such as an enlarged
      feeling of the abdomen, was reported in the balloon (+) group. CONCLUSIONS: Our
      new technique has several advantages, including reduction in the frequency of
      postoperative abdominal symptoms, and will be useful and safe for gastric ESD.

PMID- 21722179
TI  - Predicting response to therapy in chronic hepatitis C: an approach combining
      interleukin-28B gene polymorphisms and clinical data.
AB  - BACKGROUND AND AIM: Polymorphisms at the interleukin-28B (IL28B) gene predict
      therapeutic response in chronic hepatitis C virus genotype 1 (CHC-1) infection.
      The aim of the present study was to establish whether a unique single-nucleotide
      polymorphism (SNP) represents the whole predictive value of the IL28B haplotype
      for sustained viral response (SVR) and primary non-response (PNR). METHODS: SNP
      rs12979860 and rs8099917 were determined by TaqMan assays in 110 CHC-1 Caucasian
      patients treated with pegylated interferon plus ribavirin. RESULTS: There were 51
      SVR, 43 PNR, and 16 relapses. Baseline predictors of SVR were rs12979860CC
      genotype (P = 0.008), viral load < 400.000 IU/mL (P < 0.010), age (P = 0.013),
      gamma-glutamyl transferase (P = 0.022), alkaline phosphatase (P = 0.008), and
      cholesterol (P = 0.048). The area under the receiver-operating curve (AUROC) of
      the model, including these variables, was 0.841 (95% confidence interval [CI] =
      0.767-0.916). The same figures for PNR were rs12979860 T-allele carrier state (P
      = 0.00008), viral load >= 400.000 IU/mL (P = 0.007), aspartate
      aminotransferase/alanine aminotransferase (P = 0.048), and serum cholesterol (P =
      0.064), (AUROC = 0.869, 95% CI = 0.792-0.945). After excluding rs12979860CT SNP
      from multivariate analyses, the rs8099917 genotype alone did not predict SVR (P =
      0.185), but strongly predicted PNR (P = 0.003). The significance of haplotypes
      combining both SNP as predictors of SVR and PNR was higher than those of each
      separate SNP. CONCLUSIONS: The rs12979860 SNP strongly predicts therapeutic
      response in CHC-1 patients, and if associated with easy-to-obtain baseline
      criteria, provides a useful tool for the selection of candidates for antiviral
      therapy. IL28B haplotypes might improve the clinical usefulness of individual
      SNP.

PMID- 21722180
TI  - Prediction of improved liver function after balloon-occluded retrograde
      transvenous obliteration: relation to hepatic vein pressure gradient.
AB  - BACKGROUND AND AIMS: Balloon-occluded retrograde transvenous obliteration (B-RTO)
      is an effective treatment for gastric varices (GVx), as well as hepatic
      encephalopathy. The aim of this study was to examine the changes of the hepatic
      vein pressure gradient (HVPG) after B-RTO and determine the relation between the
      changes of HVPG and liver function. PATIENTS AND METHODS: B-RTO was performed in
      30 patients with GVx and hepatic encephalopathy. HVPG was measured in 19 of 30
      patients both before and after B-RTO. RESULTS: The B-RTO was successful in all
      patients. The GVx and hepatic encephalopathy were improved, and no recurrence or
      bleeding was observed within the follow- up period. The serum albumin and
      prothrombin activity were significantly improved 6 months after B-RTO in all
      patients. HVPG was elevated 44% above the baseline after B-RTO. Liver function
      significantly improved 6 months after B-RTO in patients whose HVPG increased >=
      20% from baseline. CONCLUSION: An elevated HVPG after B-RTO is one aspect of the
      effect of liver function, and an HVPG increase of >= 20% from baseline is a
      predictive factor for obtaining an improvement of liver function.

PMID- 21722181
TI  - Mitigating endoplasmic reticulum stress with revaprazan ameliorates stress
      related mucosal disease.
AB  - BACKGROUND AND AIM: The term "stress-related mucosal disease" (SRMD) represents
      conditions ranging from superficial mucosal damage to focal deep mucosal damage
      in the stomach, of which pathogenesis is deduced to be violent mucosal ischemia
      or excess oxidative stress, but not fully clarified yet. Under the hypothesis
      that mucosal cell apoptosis subsequent to endoplasmic reticulum (ER) stress might
      play a crucial role, we evaluated the efficacy and mechanism that novel acid pump
      antagonist (APA), revaprazan, alleviated water immersion restraint stress (WIRS)
      induced SRMD in rats. METHODS: In order to define whether WIRS-induced SRMD is
      associated with ER stress, we checked the alteration in the expression of ER
      stress markers including GRP78, CHOP, XBP-1, BiP as well as apoptosis in WIRS
      induced SRMD. The efficacy of revaprazan on either alleviating ER stress or
      attenuating SRMD was compared with proton pump inhibitor (PPI) and
      gastroprotectant. RESULTS: Ten hours of WIRS induced a severe degree of SRMD, in
      which ER stress markers including CHOP, XBP1, and BiP were significantly
      overexpressed in the gastric tissues. However, these markers of ER stress were
      significantly decreased in the group pretreated with revaprazan compared to PPI
      or gastroprotectant, accompanied with a significant reduction in apoptotic index.
      In addition to ER stress, revaprazan imposed anti-inflammatory benefit to limit
      SRMD based on significant levels of inflammatory cell apoptosis. CONCLUSION:
      Endoplasmic reticulum stress accompanied with drastic apoptosis was implicated in
      the development of SRMD, but revaprazan could rescue the stomach from SRMD
      through alleviating ER stress in epithelial cells much better than either PPI or
      gastroprotectant.

PMID- 21722182
TI  - Toll-like receptor 2 monoclonal antibody or/and Toll-like receptor 4 monoclonal
      antibody increase counts of Lactobacilli and Bifidobacteria in dextran sulfate
      sodium-induced colitis in mice.
AB  - BACKGROUND AND AIM: The accurate pathogenesis of ulcerative colitis (UC) is not
      yet well understood. Recently, Toll-like receptor 2 (TLR2), TLR4 and gut
      microbial flora have been proved as playing important roles in the process of UC.
      This study was to evaluate the effect of TLR2 and TLR4 monoclonal antibodies on
      gut microbial flora in dextran sulfate sodium (DSS)-induced colitis in a mouse
      model. METHODS: We evaluated the effects of the TLR2 and TLR4 monoclonal
      antibodies on the development of DSS-induced colitis. Clinical symptoms were
      evaluated by the disease activity index (DAI), while tissue samples were
      evaluated by histological scoring (HS). Meanwhile, the mucosal mRNA expressions
      of TLR2, TLR4, interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-17 were
      analyzed by Realtime polymerase chain reaction (PCR). The mucosal protein TRAF6,
      TAB1, P-IKK, P-P38alpha mitogen-activated protein kinase (MAPL) and c-jun
      expressions of the TLR2 and TLR4 signaling pathways were analyzed using Western
      blot. The mucosal nuclear factor kappa B (NF-kappaB) was analyzed using
      electrophoretic mobility shift assay. Fecal samples were obtained directly from
      the cecum for microbiological studies. RESULTS: Expressions of TLR2 and TLR4 in
      colonic epithelial cells on DSS-induced colitis were much higher than normal
      ones. After the treatment with TLR2mAb and TLR4mAb, DAI and HS were decreased
      significantly. The UC model group showed a conspicuous increase of Escherichia
      coli and decreases of Lactobacillus spp. and Bifidobacterium spp. After being
      treated with TLR2mAb or/and TLR4mAb, Lactobacillus spp. and Bifidobacterium spp.
      increased to the normal level. CONCLUSIONS: TLR2mAb and TLR4mAb can suppress the
      development of DSS-induced colitis and increase counts of Lactobacilli and
      Bifidobacteria.

PMID- 21722183
TI  - To prescribe or not to prescribe? Guidelines for spectacle prescribing in infants
      and children.
AB  - This paper discusses the considerations for prescribing a refractive correction
      in infants and children up to and including school age, with reference to the
      current literature. The focus is on children who do not have other disorders, for
      example, binocular vision anomalies, such as strabismus, significant heterophoria
      or convergence excess. However, refractive amblyogenic factors are discussed, as
      is prescribing for refractive amblyopia. Based on this discussion, guidelines are
      proposed, which indicate when to prescribe spectacles and what amount of
      refractive error should be corrected. It may be argued that these are premature
      because there are many questions that remain unanswered and we do not have the
      quality of evidence that we would like; the clinician, however, must make
      decisions on whether and what to prescribe when examining a child. These
      guidelines are to aid clinicians in their current clinical decision making.

PMID- 21722184
TI  - Reproducibility of syntax score: from core lab to real world.
AB  - AIMS: Syntax score is a significant tool in the management of complex coronary
      artery disease (CAD). This score is based on visual assessment of coronary
      lesions via coronary angiograms. It has some limitations due to its visual
      assessment. Therefore, interobserver and intraobserver agreement should be
      tested. METHODS: One hundred twenty-two coronary angiograms were examined, and 76
      in whom critical lesions were detected in the coronary arteries were included the
      study. Coronary angiograms were assessed by 2 independent interventional
      cardiologists. After 8 weeks, the same interventional cardiologists reassessed
      coronary angiograms by randomly choosing 30 patients from the first analysis.
      RESULTS: For numeric Syntax score value, both interobserver and intraobserver
      variability shows perfect agreement but interobserver variability shows high mean
      difference. Syntax score was analyzed in terms of tertiles (<=22, >22 -<=32,
      >32), it has moderate agreement for interobserver variability (weighted kappa
      value of 0.56) and substantial agreement for intraobserver variability (weighted
      kappa value of 0.69). CONCLUSION: The Syntax score reproducibility is within
      acceptable limits in real world clinical practice and it may become a significant
      tool in complex CAD management. (J Interven Cardiol 2011;24:302-306).

PMID- 21722185
TI  - Kikuchi-Fujimoto lymphadenitis in an African-American man.

PMID- 21722186
TI  - Reply to H. M. Ogmundsdottir & W. P. Holbrook by M. Ebrahimi et al.

PMID- 21722187
TI  - Comment on the paper by Ebrahimi et al published in Journal of Oral Pathology &
      Medicine, 2011; 40: 281-285.

PMID- 21722188
TI  - Submerged and transmucosal healing yield the same clinical outcomes with two
      piece implants in the anterior maxilla and mandible: interim 1-year results of a
      randomized, controlled clinical trial.
AB  - OBJECTIVES: To test whether or not transmucosal healing at two-piece implants is
      as successful as submerged placement regarding crestal bone levels and patient
      satisfaction. MATERIAL AND METHODS: Adults requiring implants in the anterior
      maxilla or mandible in regions 21-25, 11-15, 31-35 or 41-45 (WHO) were recruited
      for this randomized, controlled multi-center clinical trial of a 5-year duration.
      Randomization was performed at implantation allowing for either submerged or
      transmucosal healing. Final reconstructions were seated 6 months after
      implantation. Radiographic interproximal crestal bone levels and peri-implant
      soft tissue parameters were measured at implant placement (IP) (baseline), 6 and
      12 months. Patient satisfaction was assessed by a questionnaire. A two-sided t
      test (80% power, significance level alpha=0.05) was performed on bone-level
      changes at 6 and 12 months. RESULTS: One hundred and twenty-seven subjects were
      included in the 12-month analysis (submerged [S]: 52.5%, transmucosal [TM]:
      47.2%). From IP to 6 months, the change in the crestal bone level was -0.32 mm
      (P<0.001) for the S group and -0.29 mm (P<0.001) for the TM group. From IP to 12
      months, bone-level changes were statistically significant in both groups (S -0.47
      mm, P<0.001; TM -0.48 mm, P<0.001). The mean differences of change in the bone
      levels between the two groups were not statistically significant at either time
      point, indicating the equivalence of both procedures. For both groups, very good
      results were obtained for soft tissue parameters and for patient satisfaction.
      CONCLUSIONS: Transmucosal healing of two-piece implants is as successful as the
      submerged healing mode with respect to tissue integration and patient
      satisfaction within the first 12 months after IP.

PMID- 21722189
TI  - Reamer-mediated transalveolar sinus floor elevation without osteotome and
      simultaneous implant placement in the maxillary molar area: clinical outcomes of
      391 implants in 380 patients.
AB  - OBJECTIVES: Minimally invasive sinus elevation and augmentation using a
      transalveolar approach can reduce perioperative complications and patient
      discomfort. A specially designed reamer accomplishes this without the use of an
      osteotome or a mallet. The objective of this study is to present this technique
      with relevant clinical cases and patient outcomes. MATERIAL AND METHODS: Series
      of reamers with one cutting and one reaming edge were used to prepare an
      osteotomy site for posterior maxillary areas. A total of 391 osteotomies were
      prepared with the reamer in 380 patients, and 373 implants were placed
      simultaneously. In addition to the procedure's success parameters, levels of
      intraoperative patient comfort were monitored using a visual analogue scale.
      RESULTS: The mean height of the residual alveolar process was 5.8 (0.9) mm,
      whereas mean elevation of the sinus floor was 6.2 (0.4) mm. Eighteen (4.6%)
      Schneiderian membrane perforations occurred, and the 2-year survival rate was
      95.4%. The success rate was 92.7% in sites with thin sinus floors (< 4 mm) and
      96.4% in sites with greater bone height (> 4 mm). None of the patients
      experienced any discomfort during the procedure. CONCLUSIONS: Within the limits
      of the present study, it can be concluded that reamer-mediated transalveolar
      sinus floor elevation is a reliable method for implant placement in the posterior
      maxilla, even at sites with <= 4 mm of residual alveolar bone height. This reamer
      mediated procedure is less invasive than traditional osteotomy and can minimize
      patient discomfort during sinus floor elevation.

PMID- 21722190
TI  - Enhanced implant integration with hierarchically structured implants: a pilot
      study in rabbits.
AB  - AIM: To investigate bone-to-implant bonding for some novel surface modifications
      with a hierarchic structure and to correlate the in vivo results with surface
      roughness parameters. MATERIALS AND METHODS: Newly developed implants surfaces
      were tested in rabbits and compared with the commercially available OsseoSpeedTM
      (OS) implant. The blasted test samples were subjected to treatment in oxalic acid
      (AT-II), followed by subsequent etching in hydrofluoric acid (AT-I). Scanning
      electron microscopy and X-ray photoelectron spectroscopy were used to
      characterize the surface topography and chemical composition of the implants.
      Biomechanical testing after 6 weeks of healing was complemented with the
      quantification of fluorochromes and the results were subjected to a multivariate
      statistical analysis. RESULTS: The results show, both with biomechanical- and
      with histomorphometrical tests, that the AT-I implants with different surface
      roughness at the micro (blasting), submicro (shallow cavities) and nanolevels
      (precipitates) have a greater bone tissue integration compared with the AT-II-
      and OS implants. The 2D bone-to-implant contact (BIC) data were in accordance
      with the 3D removal torque (RTQ) results even if the former were deduced from
      implants located in spongeous-type bone and the latter in cortical bone. The
      increase in RTQ values for the test samples AT-I and AT-II compared with the
      reference complies with the slightly higher S(a) values for these surfaces.
      CONCLUSIONS: Using a combination of conventional methods with novel
      quantification of florochrome and multivariate analysis, the influence of surface
      roughness on different levels could be discriminated. The RTQ and BIC values show
      that the most hierarchical structure with submicro cavities and nanoscale
      precipitates possesses the most favourable osseointegration properties.

PMID- 21722191
TI  - Extra short dental implants supporting an overdenture in the edentulous maxilla:
      a proof of concept.
AB  - OBJECTIVES: This study investigates the outcome of short implants additionally
      placed with longer implants to support a maxillary overdenture. MATERIALS AND
      METHODS: Twelve patients received six implants to support a maxillary
      overdenture. Only one patient still had two molars in the maxilla, while the
      others had no remaining teeth. The status of the opposing arch was diverse. The
      distal implant in each quadrant was 6 mm in height (S) and the middle implants
      ranged between 10 and 14 mm (L). All implants were placed following a one-stage
      procedure and early loaded (6 weeks). Clinical and radiological parameters were
      assessed 6, 12 and 24 months after loading. RESULTS: One short implant failed 2
      weeks after surgery, probably due to early mobilization by the provisional
      prosthesis. The mean bone loss on the rough part of the implant was 0.7 mm (S)
      vs. 1.3 mm (L) during the first year and 0.3 mm (S) vs. 0.2 mm (L) during the
      second year after loading. The mean implant stability quotient values were 67 (S)
      vs. 70 (L) at placement and 75 (S) vs. 78 (L) after 1 year. At the 2-year follow-
      up, all prostheses were still stable and comfortable. CONCLUSION: An overdenture
      on six implants, of which two have a reduced length, might represent a successful
      treatment option. No significant difference could be found between both implant
      lengths at 2 years' follow-up. However, bone loss with short implants may
      increase the likelihood of failure.

PMID- 21722192
TI  - In vitro influence of ultrasonic stress, removal force preload and thermocycling
      on the retrievability of implant-retained crowns.
AB  - OBJECTIVES: The main goals of this in vitro study were to evaluate the influence
      of thermocycling, ultrasonic stress and the removal force preload on the
      retrievability of cemented implant crowns using a clinical removal device
      (Coronaflex) and evaluating the tensile strength using a universal testing
      machine (UTM). METHODS: Thirty-six crowns were cast from a Co-Cr alloy for 36
      tapered titanium abutments (5 degrees  taper, 4.3 mm diameter, 6 mm height,
      Camlog, Germany). The crowns were cemented with a glass-ionomer (Ketac Cem) or a
      polycarboxylate (Durelon) cement, followed by 3 days of storage in ionized water
      without thermocycling or 150 days of storage with 37,500 thermal cycles between 5
      degrees C and 55 degrees C. Before removal, the crowns were subjected to
      ultrasonic stress for 0, 5 or 10 min with a contact pressure of either 50 or 500
      g. The Coronaflex was used with a removal force preload of 50 or 400 cN,
      respectively, applied on the point of loading. Scanning electronic microscopy
      (SEM) was used to evaluate the impact of the removal on the abutment screws.
      RESULTS: Crowns cemented with the glass-ionomer cement were significantly easier
      to remove with the Coronaflex or the UTM than crowns cemented with the
      polycarboxylate cement (P<=0.05). Ultrasonic stress showed no significant impact
      on the retrievability regardless of the contact pressure or duration applied
      (P>0.05). No significant differences could be found for both cements when removed
      with the Coronaflex or the UTM (P>0.05) after thermocycling was applied. A
      removal force preload of 400 cN resulted in significantly reduced removal
      attempts in comparison with 50 cN for both cements (P<=0.05). CONCLUSIONS:
      Ultrasound and thermal cycling did not result in reduced cement strength, but to
      retrieve the crowns, the full impact of a removal instrument has to be applied.
      Ketac Cem can be used as a "semipermanent" solution, whereas Durelon might serve
      for permanent cementation. None of the abutment screws showed signs of wear
      caused by the removal process.

PMID- 21722193
TI  - Long-term outcomes of three types of implant-supported mandibular overdentures in
      smokers.
AB  - PURPOSE: The aim of the study was to compare the differences in the long-term
      clinical and radiologic effects for three different treatment strategies with
      implant-supported overdentures in the edentulous mandible, with a special
      emphasis on smoking. MATERIALS AND METHODS: In a randomized- controlled clinical
      trial, 110 edentulous patients participated. Thirty-six patients were treated
      with an overdenture supported by two implants with ball attachments (2IBA), 37
      patients with an overdenture supported by two implants with a bar (2ISB) and 37
      patients with an overdenture supported by four implants with a triple bar (4ITB).
      After a mean evaluation period of 8.3 years, the clinical and radiographic
      parameters were evaluated. RESULTS: Ninety-four out of the original 110 patients
      (=85%) were evaluated. In the 2IBA group, the plaque index was significantly
      lower (vs. 2ISB, P=0.013; vs. 4ITB, P=0.001) than in the other groups, but there
      was no correlation with the other peri-implant parameters. In the 4ITB group, the
      marginal bone loss was significantly higher than that in the two implant groups.
      The maximal probing depth was correlated with peri-implant bone loss (P=0.011).
      Smoking almost doubled marginal bone loss irrespective of the treatment strategy
      chosen. CONCLUSIONS: Patients with two implants show less marginal bone loss than
      those with four implants. Smoking is a risk factor for the survival of dental
      implants in the long run.

PMID- 21722194
TI  - The effect of permanent grafting materials on the preservation of the buccal bone
      plate after tooth extraction: an experimental study in the dog.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effects of a novel
      bone substitute system (Natix((r))), consisting of porous titanium granules (PTG)
      and a bovine-derived xenograft (Bio-Oss((r))), on hard tissue remodelling
      following their placement into fresh extraction sockets in dogs. MATERIAL AND
      METHODS: Six modalities were tested; Natix((r)) granules with and without a
      covering double-layered Bio Gide((r)) membrane; Bio-Oss((r)) with and without a
      covering double-layered Bio Gide((r)) membrane; and a socket left empty with and
      without a covering double-layered Bio Gide((r)) membrane. Linear measurements,
      indicative of buccal bone height loss, and an area measurement indicative of
      buccal bulk bone loss were made. The statistical analysis was based on the Latin
      Square design with two blocking factors (dog and site). Tukey's post hoc test was
      used to adjust for multiple comparisons. RESULTS: Histological observation
      revealed that while bone formed around both the xenograft and the titanium
      particles, bone was also noted within titanium granules. Of the five modalities
      of ridge preservation techniques used in this study, no one technique proved to
      be superior. CONCLUSION: The titanium granules were observed to have promising
      osseoconductive properties.

PMID- 21722195
TI  - Model-based guided implant insertion for solitary tooth replacement: a pilot
      study.
AB  - OBJECTIVE: The impact of the implant position on the restorative outcome could
      justify guided surgery even for the single implants particularly in the aesthetic
      zone and especially when a simplified concept is available. MATERIAL AND METHODS:
      Based on a plaster model, on which the soft tissues were mimicked (according to
      the thickness measured on a Cone-Beam CT), a tooth-supported, surgical template
      was prepared. The latter guided all drills so that even flapless implant
      insertion became possible. All implants were placed by students of the master
      after-master training program in Periodontology. RESULTS: The prospective cohort
      included a total of 34 implants, all of AstraTech (Osteospeed((r))) type, which
      were successfully inserted in 29 patients, 16 flapless, 32 onestage. The marginal
      bone along the integrated implants remained stable over time, with 0.13 mm loss
      during the first year. The aesthetic parameters were reassuring. CONCLUSIONS:
      This simple model-based concept seems to be reliable for the guided placement of
      single implants and the pre-operative preparation of their restorations.

PMID- 21722196
TI  - Bone tissue microarchitectural characteristics at dental implant sites. Part 1:
      identification of clinical-related parameters.
AB  - OBJECTIVE: To identify the characteristics of bone tissue microarchitecture by
      microCT at dental implant bone sites, describing them in terms of clinical
      parameters. MATERIAL AND METHODS: Forty-six bone implant sites of the maxilla and
      mandible from 32 volunteers were evaluated by conventional radiographs and CT
      scans. During the installation of each implant, bone biopsies were removed using
      a trephine bur at the first drilling to prepare the socket implant. Each sample
      was evaluated by microCT and dimensional parameters measured. RESULTS: Factor
      analysis summarized the microparameters into four components, which accounted for
      92.8% of the total variance. The identified factors were (1) architecture -
      variables affecting 3D trabecular bone configuration and organization, (2)
      density - variables relating to surface/volume ratios and volume/volume ratios,
      (3) bulk - variables relating to the amount of bone and (4) spacing - variable
      related to the distance between trabeculae and the quantity and organization of
      marrow spaces. CONCLUSION: These four summarized factors correspond to clinical
      and radiographically recognizable parameters used for routine bone quality
      evaluation for implant treatment planning, which can potentially influence the
      primary stability of dental implants. The understanding of factors related to
      bone microarchitecture might reveal important aspects of its mechanical
      properties, essential for implant success.

PMID- 21722197
TI  - Evaluation of dietary stevioside supplementation on anti-human serum albumin
      immunoglobulin G, Alpha-1-glycoprotein, body weight and thyroid hormones in
      broiler chickens.
AB  - Sixty male broiler chickens fed a diet supplemented with 130 mg/kg stevioside (S
      group) or an unsupplemented diet (C group) from day 1 of age onwards. On day 21
      of age, ten birds from either the S (SH) or C (CH) group were injected
      subcutaneously with 100 MUg human serum albumin (HSA) and ten others from either
      S (SP) or C (CP) group injected with 100 MUl phosphate-buffered saline (PBS) in
      the same way. There were no significant effect of supplementation nor interaction
      with age on average body weights, T(3) and T(4) concentrations of non-injected
      chickens. After the primary immunization, alpha(1) -glycoprotein concentrations
      increased in all treatment groups except the CP group, and were significantly
      higher in the CH group in relation to the other groups. Fourteen and 18 days
      after the primary immunization, HSA injected chickens of both dietary treatments
      had significantly higher anti-HSA immunoglobulin G (IgG) levels than their PBS
      injected controls. No effect of stevioside supplementation was observed for IgG
      level. In conclusion, dietary stevioside inclusion can attenuate the pro
      inflammatory response after stimulation of the innate immune response in broiler
      chickens.

PMID- 21722198
TI  - Orthotopic bladder substitute in renal transplant recipients: experience with
      Studer technique and literature review.
AB  - Renal transplant recipients with high-risk bladder cancer following cystectomy
      need a urinary diversion preserving the renal function and possibly maintaining
      body image, while still offering the best oncological outcome. The aim of this
      report is to describe our experience of radical cystectomy and orthotopic ileal
      neobladder with Studer technique in this population, and to review the
      literature. We performed radical cystectomy and Studer ileal neobladder in four
      male patients (median age 67 years) after median time of 9.5 years following
      renal transplantation. Pathology revealed pT1HGN+ transitional cell carcinoma in
      one case, pT1HGN0 in two and pT3aHGN0 in one. Two patients presenting aggressive
      disease (N+ and pT3a) died of tumour progression after 20 and 14 months,
      respectively, while the other two are alive after 56 and 36 months of follow-up
      with no evidence of disease, stable serum creatinine (2.29 and 1.6 mg/dl) and
      mild metabolic acidosis. Day and night-time urinary continence were satisfactory
      in all patients. Good functional outcomes have been reported in the 20 cases of
      ileal orthotopic neobladder with different techniques published so far and the
      global experience of 24 cases with a median follow-up of 39 months documents a
      cancer specific survival of 62.5%.

PMID- 21722199
TI  - Caution: deceased donor organ commercialism!
AB  - In the past 3 years there have been attempts to counter the international
      campaign against a market in organs from the living. In parallel to these
      attempts, support for a market in organs from the deceased has gained some
      traction. In this article we describe the various forms of this phenomenon,
      analyze its implications, and call upon policy makers to take steps to halt its
      progress.

PMID- 21722200
TI  - Standardized video-assisted retroperitoneal minilaparotomy surgery for 615 living
      donor nephrectomies.
AB  - To increase the rate of living kidney donation, the long-term safety of
      nephrectomy must be demonstrated to potential donors. We analyzed long-term donor
      outcomes and evaluated the standardization of surgical technique. We evaluated
      615 donors who underwent Video-assisted minilaparotomy living donor nephrectomy
      (VLDN) at Yonsei Severance Hospital between 2003 and 2009. Perioperative data and
      predictors of outcomes were prospectively analyzed. The mean operative time and
      mean warm ischemia time were 192.7 and 2.2 min, respectively. Mean estimated
      blood loss was 195.3 ml. The mean post-transplant serum creatinine levels and
      Modification of Diet in Renal Disease study equation for estimating glomerular
      filtration rate were 1.1 mg/dl and 68 ml/min/1.73 m(2) , respectively at 5 years
      after VLDN. The intra-operative and postoperative complication rate were 3.1% and
      6.3%, respectively. Delayed renal function, 5-year graft survival, and
      complication rates of recipients were 1.1%, 98.4%, and 0.4%, respectively.
      Predictors of operative time were medical history, vessel anomaly, and surgeon
      experience (>50 cases). The single predictor of intra-operative complications was
      vessel anomaly. Standardized VLDN is feasible and safe. Our data on long-term
      outcomes can assist in demonstrating the long-term safety of donor nephrectomy to
      potential donors. To compare VLDN to other types of donor nephrectomy, a
      prospective multicenter study must be performed.

PMID- 21722201
TI  - InlB-mediated Listeria monocytogenes internalization requires a balanced
      phospholipase D activity maintained through phospho-cofilin.
AB  - Internalization of Listeria monocytogenes into non-phagocytic cells is tightly
      controlled by host cell actin dynamics and cell membrane alterations. However,
      knowledge about the impact of phosphatidylcholine cleavage driven by host cell
      phospholipase D (PLD) on Listeria internalization into epithelial cells is
      limited. Here, we report that L. monocytogenes activates PLD in Vero cells during
      the internalization. With immunostaining it was shown that both PLD1 and PLD2
      surrounded partially or completely the phagocytic cup of most L. monocytogenes.
      Either up- or down-regulation of PLD expression (activity) diminished Listeria
      internalization. Both PLD1 and PLD2 in Vero cells were required for efficient
      Listeria internalization, and could substitute for each other in the regulation
      of Listeria internalization. Further, exogenous InlB activated host cell PLD1 and
      PLD2 via the Met receptor, and restored host PLD activation by InlB-deficient L.
      monocytogenes. InlB-induced PLD activation and Listeria internalization were
      tightly controlled by phospho-cycling of cofilin. PLD1, but not PLD2, was
      involved in cofilin-mediated PLD activation and Listeria internalization. These
      data indicate that cofilin-dependent PLD activation induced by InlB may represent
      a novel regulation mechanism for efficient Listeria internalization into
      epithelial cells.

PMID- 21722202
TI  - Global analysis of phase variation in Myxococcus xanthus.
AB  - Myxococcus xanthus can vary its phenotype or 'phase' to produce colonies that
      contain predominantly yellow or tan cells that differ greatly in their abilities
      to swarm, survive and develop. Yellow variants are proficient at swarming (++)
      and tend to lyse in liquid during stationary phase. In contrast, tan variants are
      deficient in swarming (+) and persist beyond stationary phase. The phenotypes and
      transcriptomes of yellow and tan variants were compared with mutants affected in
      phase variation. Thirty-seven genes were upregulated specifically in yellow
      variants including those for production of the yellow pigment, DKxanthene. A
      mutant in DKxanthene synthesis produced non-pigmented (tan) colonies but still
      phase varied for swarming suggesting that pigmentation is not the cause of phase
      variation. Disruption of a gene encoding a HTH-Xre-like regulator, highly
      expressed in yellow variants, abolished pigment production and blocked the
      ability of cells to switch from a swarm ++ to a swarm (+) phenotype, showing that
      HTH-Xre regulates phase variation. Among the four genes whose expression was
      increased in tan variants was pkn14, which encodes a serine-threonine kinase that
      regulates programmed cell death in Myxococcus via the MrpC-MazF toxin-antitoxin
      complex. High levels of phosphorylated Pkn14 may explain why tan cells enjoy
      enhanced survival.

PMID- 21722203
TI  - Site-specific accretion of an integrative conjugative element together with a
      related genomic island leads to cis mobilization and gene capture.
AB  - Genomic islands, flanked by attachment sites, devoid of conjugation and
      recombination modules and related to the integrative and conjugative element
      (ICE) ICESt3, were previously found in Streptococcus thermophilus. Here, we show
      that ICESt3 transfers to a recipient harbouring a similar engineered genomic
      island, CIMEL3catR3, and integrates by site-specific recombination into its
      attachment sites, leading to their accretion. The resulting composite island can
      excise, showing that ICESt3 mobilizes CIMEL3catR3, in cis. ICESt3, CIMEL3catR3,
      and the whole composite element can transfer from the strain harbouring the
      composite structure. The ICESt3 transfer to a recipient bearing CIMEL3catR3, can
      also lead to retromobilization, i.e. its capture by the donor. This is the first
      demonstration of specific conjugative mobilization of a genomic island in cis and
      the first report of ICE-mediated retromobilization. CIMEL3catR3, would be the
      prototype of a novel class of non-autonomous mobile elements (CIMEs: CIs
      mobilizable elements), which hijack the recombination and conjugation machinery
      of related ICEs to excise, transfer and integrate. Few genome analyses have shown
      that CIMEs could be widespread and have revealed internal repeats that could
      result from accretions in numerous genomic islands, suggesting that accretion and
      cis mobilization have a key role in evolution of genomic islands.

PMID- 21722204
TI  - Why would you pay to get published?

PMID- 21722205
TI  - Rhythmic intrinsic bursting neurons in human neocortex obtained from pediatric
      patients with epilepsy.
AB  - Neocortical oscillations result from synchronized activity of a synaptically
      coupled network and can be strongly influenced by the intrinsic firing properties
      of individual neurons. As such, the intrinsic electroresponsive properties of
      individual neurons may have important implications for overall network function.
      Rhythmic intrinsic bursting (rIB) neurons are of particular interest, as they are
      poised to initiate and/or strongly influence network oscillations. Although
      neocortical rIB neurons have been recognized in multiple species, the current
      study is the first to identify and characterize rIB neurons in the human
      neocortex. Using whole-cell current-clamp recordings, rIB neurons (n = 12) are
      identified in human neocortical tissue resected from pediatric patients with
      intractable epilepsy. In contrast to human regular spiking neurons (n = 12),
      human rIB neurons exhibit rhythmic bursts of action potentials at frequencies of
      0.1-4 Hz. These bursts persist after blockade of fast excitatory
      neurotransmission and voltage-gated calcium channels. However, bursting is
      eliminated by subsequent application of the persistent sodium current (I(NaP))
      blocker, riluzole. In the presence of riluzole (either 10 or 20 MUm), human rIB
      neurons no longer burst, but fire tonically like regular spiking neurons. These
      data demonstrate that I(NaP) plays a critical role in intrinsic oscillatory
      activity observed in rIB neurons in the human neocortex. It is hypothesized that
      aberrant changes in I(NaP) expression and/or function may ultimately contribute
      to neurological diseases that are linked to abnormal network activity, such as
      epilepsy.

PMID- 21722206
TI  - Cracking the almond (Commentary on Prevost et al.).

PMID- 21722207
TI  - The antidepressant fluoxetine but not citalopram suppresses synapse formation and
      synaptic transmission between Lymnaea neurons by perturbing presynaptic and
      postsynaptic machinery.
AB  - Depression is a debilitating mental disorder, and selective serotonin reuptake
      inhibitors (SSRIs) constitute the first-line antidepressant treatment choice for
      the clinical management of this illness; however, the mechanisms underlying their
      therapeutic actions and side effects remain poorly understood. Here, we compared
      the effects of two SSRIs, fluoxetine and citalopram, on synaptic connectivity and
      the efficacy of cholinergic synaptic transmission between identified presynaptic
      and postsynaptic neurons from the mollusc Lymnaea. The in vitro paired cells were
      exposed to clinically relevant concentrations of the two SSRIs under chronic and
      acute experimental conditions, and the incidence of synapse formation and the
      efficacy of synaptic transmission were tested electrophysiologically and with
      fluorescent Ca(2+) imaging. We demonstrate that chronic exposure to fluoxetine,
      but not to citalopram, inhibits synapse formation and reduces synaptic strength,
      and that these effects are reversible following prolonged drug washout. At the
      structural level, we demonstrate that fluoxetine, but not citalopram, prevents
      the expression and localization of the presynaptic protein synaptophysin. Acute
      exposure to fluoxetine substantially reduced synaptic transmission and synaptic
      plasticity (post-tetanic potentiation) in established synapses, whereas
      citalopram reduced synaptic transmission, but not short-term synaptic plasticity.
      We further demonstrate that fluoxetine, but not citalopram, directly inhibits
      voltage-gated Ca(2+) currents in the presynaptic neuron, as well as postsynaptic
      responsiveness to exogenously applied neurotransmitter. This study provides the
      first direct evidence that fluoxetine and citalopram exert characteristic, non
      specific side effects that are unrelated to their function as SSRIs, and that
      fluoxetine is more detrimental to synaptic physiology and structure than
      citalopram.

PMID- 21722208
TI  - Mitochondrial calcium and its regulation in neurodegeneration induced by
      oxidative stress.
AB  - A proposed mechanism of neuronal death associated with a variety of
      neurodegenerative diseases is the response of neurons to oxidative stress and
      consequent cytosolic Ca(2+) overload. One hypothesis is that cytosolic Ca(2+)
      overload leads to mitochondrial Ca(2+) overload and prolonged opening of the
      permeability transition pore (PTP), resulting in mitochondrial dysfunction.
      Elimination of cyclophilin D (CyPD), a key regulator of the PTP, results in
      neuroprotection in a number of murine models of neurodegeneration in which
      oxidative stress and high cytosolic Ca(2+) have been implicated. However, the
      effects of oxidative stress on the interplay between cytosolic and mitochondrial
      Ca(2+) in adult neurons and the role of the CyPD-dependent PTP in these dynamic
      processes have not been examined. Here, using primary cultured cerebral cortical
      neurons from adult wild-type (WT) mice and mice missing cyclophilin D (CyPD-KO),
      we directly assess cytosolic and mitochondrial Ca(2+) , as well as ATP levels,
      during oxidative stress. Our data demonstrate that during acute oxidative stress
      mitochondria contribute to neuronal Ca(2+) overload by release of their Ca(2+)
      stores. This result contrasts with the prevailing view of mitochondria as a
      buffer of cytosolic Ca(2+) under stress conditions. In addition, we show that
      CyPD deficiency reverses the release of mitochondrial Ca(2+) , leading to lower
      of cytosolic Ca(2+) levels, attenuation of the decrease in cytosolic and
      mitochondrial ATP, and a significantly higher viability of adult CyPD-knockout
      neurons following exposure of neurons oxidative stress. The study offers a first
      insight into the mechanism underlying CyPD-dependent neuroprotection during
      oxidative stress.

PMID- 21722209
TI  - Lipopolysaccharide-induced tau phosphorylation and kinase activity--modulation,
      but not mediation, by corticotropin-releasing factor receptors.
AB  - Clinical studies suggest that exposure to stress can increase risk for
      Alzheimer's disease (AD). Although the precise links between stress and
      vulnerability to develop AD remain uncertain, recent animal work suggests that
      stress may promote susceptibility to AD pathology by activating tau kinases and
      inducing tau phosphorylation (tau-P). Our previous findings indicate the
      differential involvement of corticotropin-releasing factor receptor (CRFR) types
      1 and 2 in regulating tau-P in the hippocampus induced by acute restraint, an
      emotional stressor. To assess the generality of CRFR involvement in stress
      induced tau-P and tau kinase activity, the present study extends our
      investigation to a well-characterized physiological stressor, i.e. immune
      challenge induced by bacterial lipopolysaccharide (LPS). Acute systemic
      administration of LPS (100 MUg/kg) robustly increased hippocampal (but not
      isocortical or cerebellar) tau-P, peaking at 40-120 min postinjection and abating
      thereafter. Assessments of the genotype dependence of this effect yielded results
      that were distinct from the restraint model. Treatment with LPS increased
      phosphorylation in wild-type, single and double CRFR knockouts with only subtle
      variation, which included a reliable exaggeration of tau-P responses in CRFR1
      deficient mice. Parallel analyses implicated glycogen synthase kinase-3 and
      cyclin-dependent kinase-5 as likely cellular mediators of LPS-induced tau-P.
      Conversely, our data suggest that temperature-dependent fluctuations in tau
      protein phosphatase 2A (PP2A) may not play a role in this context. Thus, neither
      the strict CRFR1 dependence of restraint-induced tau-P nor the exaggeration of
      these responses in CRFR2 null mice generalize to the LPS model. CRFR mediation of
      stress-induced hippocampal tau-P may be limited to emotional stressors.

PMID- 21722211
TI  - Effects of divalent cations on slow unblock of native NMDA receptors in mouse
      neocortical pyramidal neurons.
AB  - The N-methyl-D-aspartate receptor (NMDAR) exhibits strong voltage-dependent block
      by extracellular Mg(2+) , which is relieved by sustained depolarization and
      glutamate binding, and which is central to the function of the NMDAR in synaptic
      plasticity. Rapid membrane depolarization during agonist application reveals a
      slow unblock of NMDARs, which has important functional implications, for example
      in the generation of NMDAR spikes, and in determining the narrow time window for
      spike-timing-dependent plasticity. However, its mechanism is still unclear. Here,
      we study unblock of divalent cations in native NMDARs in nucleated patches
      isolated from mouse cortical layer 2/3 pyramidal neurons. Comparing unblock
      kinetics of NMDARs in the presence of extracellular Mg(2+) or in nominally zero
      Mg(2+) , and with Mn(2+) or Co(2+) substituting for Mg(2+) , we found that the
      properties of slow unblock were determined by the identity of the blocking metal
      ion at the binding site, presumably by affecting the operation of a structural
      link to channel gating. The time course of slow unblock was not affected by zinc,
      or the zinc chelator TPEN [N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine],
      while the slower fraction of unblock was reduced by ifenprodil, an NR2B-selective
      antagonist. Slow unblock was only weakly temperature dependent, speeding up with
      rise in temperature with a Q(10) of ~1.5. Finally, using action potential
      waveform voltage-clamp, we show that this slow relief from divalent cation block
      is a prominent feature in physiologically realistic patterns of changing membrane
      potential.

PMID- 21722210
TI  - Mechanism behind gamma band activity in the pedunculopontine nucleus.
AB  - The pedunculopontine nucleus (PPN), part of the reticular activating system,
      modulates waking and paradoxical sleep. During waking and paradoxical sleep, EEG
      responses are characterized by low-amplitude, high-frequency oscillatory activity
      in the beta-gamma band range (~20-80 Hz). We have previously reported that gamma
      band activity may be intrinsically generated by the membrane
      electroresponsiveness of PPN neurons, and that the neuronal ensemble generates
      different patterns of gamma activity in response to specific transmitters. This
      study attempted to identify the voltage-gated calcium and potassium channels
      involved in the rising and falling phases of gamma oscillations in PPN neurons.
      We found that all rat (8-14 day) PPN cell types showed gamma oscillations in the
      presence of TTX and synaptic blockers when membrane potential was depolarized
      using current ramps. PPN neurons showed gamma oscillations when voltage-clamped
      at holding potentials above -30 mV, suggesting that their origin may be spatially
      located beyond voltage-clamp control. The average frequency for all PPN cell
      types was 23 +/- 1 Hz and this increased under carbachol (47 +/- 2 Hz; anova df =
      64, t = 12.5, P < 0.001). The N-type calcium channel blocker omega-conotoxin-GVIA
      partially reduced gamma oscillations, while the P/Q-type blocker omega-agatoxin
      IVA abolished them. Both omega-CgTX and omega-Aga blocked voltage-dependent
      calcium currents, by 56 and 52% respectively. The delayed rectifier-like
      potassium channel blocker alpha-dendrotoxin also abolished gamma oscillations. In
      carbachol-induced PPN population responses, omega-agatoxin-IVA reduced higher,
      and omega-CgTx mostly lower, frequencies. These results suggest that voltage
      dependent P/Q- and, to a lesser extent, N-type calcium channels mediate gamma
      oscillations in PPN.

PMID- 21722212
TI  - Perinatal exposure to alcohol disturbs spatial learning and glutamate
      transmission-related gene expression in the adult hippocampus.
AB  - Perinatal exposure to alcohol (PEA) induces general developmental and specific
      neuropsychiatric disturbances accompanied by disturbed synaptic plasticity. Here
      we studied the long-term behavioral consequences of PEA and investigated
      glutamate transmission-related genes in a longitudinal fashion. After delivery,
      female Wistar rats and their pups were exposed to ethanol until postnatal day
      (PD)8 in vapor chambers. At the age of 5 months, the animals were behaviorally
      characterized. At both PD8 and after the behavioral testing we examined the
      expression of the vesicular glutamate transporter 1 and excitatory amino acid
      transporter (EAAT)1-4, as well as the N-methyl-D-aspartate receptor subunits
      (NR)1 and 2A-D, and in parallel receptor binding using (3) H-dizocilpine maleate
      receptor autoradiography. We found highly significant reductions of body weight
      and length following PEA in pups at PD8. These alterations disappeared in
      adulthood, when no changes of motor activity and only subtle differences of
      anxiety-related behavior were observed. It also did not affect T-maze learning,
      but had a pronounced effect on hippocampus-dependent spatial learning (Morris
      water maze testing). This specific learning deficit was accompanied by a
      dysregulation in hippocampal gene expression (significant induction of vesicular
      glutamate transporter 1, EAAT1, EAAT3, NR2A, 2B, 2C and 2D). Most of the examined
      genes turned out to be dysregulated to a higher degree at the age of 5 months. We
      therefore conclude that perinatal ethanol toxicity alters the plasticity of
      neurodevelopment and the regulation of glutamatergic gene expression, which may
      result in specific hippocampus-dependent learning deficits in adulthood.

PMID- 21722213
TI  - Spatiotemporal specificity of GABAA receptor-mediated regulation of adult
      hippocampal neurogenesis.
AB  - GABAergic transmission regulates adult neurogenesis by exerting negative feedback
      on cell proliferation and enabling dendrite formation and outgrowth. Further,
      GABAergic synapses target differentiating dentate gyrus granule cells prior to
      formation of glutamatergic connections. GABA(A) receptors (GABA(A) Rs) mediating
      tonic (extrasynaptic) and phasic (synaptic) transmission are molecularly and
      functionally distinct, but their specific role in regulating adult neurogenesis
      is unknown. Using global and single-cell targeted gene deletion of subunits
      contributing to the assembly of GABA(A) Rs mediating tonic (alpha4, delta) or
      phasic (alpha2) GABAergic transmission, we demonstrate here in the dentate gyrus
      of adult mice that GABA(A) Rs containing alpha4, but not delta, subunits mediate
      GABAergic effects on cell proliferation, initial migration and early dendritic
      development. In contrast, alpha2-GABA(A) Rs cell-autonomously signal to control
      positioning of newborn neurons and regulate late maturation of their dendritic
      tree. In particular, we observed pruning of distal dendrites in immature granule
      cells lacking the alpha2 subunit. This alteration could be prevented by
      pharmacological inhibition of thrombospondin signaling with chronic gabapentin
      treatment, shown previously to reduce glutamatergic synaptogenesis. These
      observations point to homeostatic regulation of inhibitory and excitatory inputs
      onto newborn granule cells under the control of alpha2-GABA(A) Rs. Taken
      together, the availability of distinct GABA(A) R subtypes provides a molecular
      mechanism endowing spatiotemporal specificity to GABAergic control of neuronal
      maturation in adult brain.

PMID- 21722214
TI  - Meal anticipatory rise in acylated ghrelin at dark onset is blunted after long
      term fasting in rats.
AB  - Ghrelin is a 28 amino acid acylated peptide originally characterised for its
      capacity to stimulate growth hormone secretion. Ghrelin is also an orexigenic and
      adipogenic hormone and is thought to be a signal to increase locomotor activity
      in anticipation of a scheduled meal. Although ghrelin is considered to be up
      regulated during fasting, there are still conflicting data regarding the impact
      of starvation on ghrelin secretion. To test whether the secretory pattern of
      acylated ghrelin is altered during fasting, plasma levels were monitored every 20
      min for 6 h in freely-behaving rats at the light/dark cycle transition, when
      animals initiate feeding and activity and use preferentially free fatty acids
      (FFA) as a source of energy. Rats were fed ad lib. or fasted at dark onset for
      24, 48 or 72 h, with or without refeeding rate. The anticipatory rise in ghrelin
      levels, as well as home-cage activity at the onset of darkness, was significantly
      reduced from 48 h of fasting compared to ad lib. conditions. A delayed ghrelin
      peak, sensitive to renutrition, was observed in fasted animals. Although their
      motivation to eat appeared to be intact, rats fasted for 72 h showed the smallest
      compensatory refeeding rate after fasting, possibly reflecting altered gut
      function. Expression of agouti-related protein and neuropeptide Y, was
      significantly increased in 48- and 72-h fasted animals. Thus, following fasting,
      a blunted acylated ghrelin secretion at dark onset (i.e. a period when animals
      depend on FFA as a source of energy) is associated with reduced locomotor
      activity and refeeding and an up-regulation of anabolic neuropeptides. Such
      changes could be interpreted as compensatory mechanisms for helping to conserve
      energy under conditions where food is not available.

PMID- 21722215
TI  - A bold view of the lactating brain: functional magnetic resonance imaging studies
      of suckling in awake dams.
AB  - Functional magnetic resonance imaging (fMRI) has been used to investigate the
      responsiveness of the maternal rat brain to pup-suckling under various
      experimental paradigms. Our research employing the lactating rat model has
      explored the cortical sensory processing of pup stimuli and the effect of
      suckling on the brain's reward system. Suckling was observed to increase blood
      oxygen-level-dependent (BOLD) signal intensity in the midbrain, striatum and
      prefrontal cortex, which are areas that receive prominent dopaminergic inputs.
      The BOLD activation of the reward system occurs in parallel with the activation
      of extensive cortical sensory areas. The observed regions include the olfactory
      cortex, auditory cortex and gustatory cortex, and could correspond to cortical
      representations of pup odours, vocalisations and taste that are active during
      lactation. Activation patterns within reward regions are consistent with past
      research on maternal motivation and we explore the possibility that exposure to
      drugs of abuse might be disruptive of maternal neural responses to pups,
      particularly in the prefrontal cortex. Our ongoing fMRI studies support and
      extend past research on the maternal rat brain and its functional neurocircuitry.

PMID- 21722217
TI  - Oestradiol regulates beta-catenin-mediated transcription in neurones.
AB  - Oestradiol acts in the brain by multiple mechanisms, including the regulation of
      transcriptional activity through classical oestrogen receptors, alpha and beta,
      and by the activation of membrane/cytoplasm-initiated signalling cascades. In
      neuroblastoma cells, primary neurones in culture and in the brain in vivo,
      oestradiol activates the phosphoinositide 3-kinase/Akt/glycogen synthase kinase 3
      signalling pathway by a mechanism involving oestrogen receptor alpha. Through
      this pathway, oestradiol regulates the stability of beta-catenin, induces the
      translocation of beta-catenin to the cell nucleus and regulates beta-catenin
      mediated transcription through the T cell factor/DNA complex. Genomic analyses in
      neuroblastoma cells have revealed that the set of genes regulated by oestradiol
      through beta-catenin is not identical to that regulated by the Wnt signalling
      pathway, revealing a new mechanism for oestradiol signalling in neurones.

PMID- 21722216
TI  - Oestrogen signalling and neuroprotection in cerebral ischaemia.
AB  - 17beta-Oestradiol (E(2)) is an important hormone signal that regulates multiple
      tissues and functions in the body. This review focuses on the neuroprotective
      actions of E(2) in the brain against cerebral ischaemia and the potential
      underlying mechanisms. A particular focus of the review will be on the role of
      E(2) to attenuate NADPH oxidase activation, superoxide and reactive oxygen
      species generation and reduce oxidative stress in the ischaemic brain as a
      potentially key neuroprotective mechanism. Evidence of a potential novel role of
      extranuclear oestrogen receptors in mediating E(2) signalling and neuroprotective
      actions is also discussed. An additional subject is the growing evidence
      indicating that periods of long-term oestrogen deprivation, such as those
      occurring after menopause or surgical menopause, may lead to loss or attenuation
      of E(2) signalling and neuroprotective actions in the brain, as well as enhanced
      sensitivity of the hippocampus to ischaemic stress damage. These findings have
      important implications with respect to the 'critical period hypothesis', which
      proposes that oestrogen replacement must be initiated at peri-menopause in humans
      to exert its beneficial cardiovascular and neural effects. The insights gained
      from these various studies will prove valuable for guiding future directions in
      the field.

PMID- 21722219
TI  - Reciprocal expression of IL-25 and IL-17A is important for allergic airways
      hyperreactivity.
AB  - BACKGROUND: Interleukin (IL)-25 (IL-17E) is a potent inducer of the type-2 immune
      effector response. Previously we have demonstrated that a neutralizing anti-IL-25
      antibody, given during the establishment of ovalbumin-specific lung allergy,
      abrogates airways hyperreactivity. OBJECTIVE: Blocking IL-25 results in the
      suppression of IL-13, a cytokine known to exacerbate pulmonary inflammation, and
      an unexpected reciprocal increase in IL-17A. The role of IL-17A in asthma is
      complex with reports of both pro-inflammatory and anti-inflammatory functions.
      Our aim was to determine the influence of IL-17A in regulating IL-25-dependent
      lung allergy. METHOD: Neutralizing antibodies to IL-25 and/or IL-17A were
      administered during an experimental model of allergic asthma. Bronchoalveolar
      cell infiltrates and lung cytokine production were determined to assess lung
      inflammation. Invasive plethysmography was undertaken to measure lung function.
      RESULTS: Neutralization of IL-25 correlated with a decrease in IL-13 levels and
      an increase in IL-17A production, and an accompanying prevention of airway
      hyperresponsiveness (AHR). Notably, the blocking of IL-17A reversed the
      protective effects of treating with anti-IL-25 antibodies, resulting in the re
      expression of several facets of the lung inflammatory response, including IL-13
      and eotaxin production, eosinophilia and AHR. Using mice over-expressing IL-13 we
      demonstrate that treatment of these mice with anti-IL-25 fails to suppress IL-13
      levels and in turn IL-17A levels remain suppressed. CONCLUSIONS AND CLINICAL
      RELEVANCE: IL-13 is known to be an important inducer of lung inflammation,
      causing goblet cell hyperplasia and promoting airways hyperreactivity. Our data
      now demonstrate that IL-13 also plays an important role in the genesis of lung
      inflammation downstream of IL-25 by suppressing a protective IL-17A response.
      These findings also highlight the important reciprocal interplay of the IL-17
      family members, IL-25 and IL-17A, in regulating allergic lung responses and
      suggest that the balance of IL-17A, together with IL-25, will be an important
      consideration in the treatment of allergic asthma.

PMID- 21722220
TI  - Specific expression of LATERAL SUPPRESSOR is controlled by an evolutionarily
      conserved 3' enhancer.
AB  - Aerial plant architecture is largely based on the activity of axillary meristems
      (AMs), initiated in the axils of leaves. The Arabidopsis gene LATERAL SUPPRESSOR
      (LAS), which is expressed in well-defined domains at the adaxial boundary of leaf
      primordia, is a key regulator of AM formation. The precise definition of organ
      boundaries is an essential step for the formation of new organs in general and
      for meristem initiation; however, mechanisms leading to these specific patterns
      are not well understood. To increase understanding of how the highly specific
      transcript accumulation in organ boundary regions is established, we investigated
      the LAS promoter. Analysis of deletion constructs revealed that an essential
      enhancer necessary for complementation is situated about 3.2 kb downstream of the
      LAS open reading frame. This enhancer is sufficient to confer promoter
      specificity as upstream sequences in LAS could be replaced by non-specific
      promoters, such as the 35S minimal promoter. Further promoter swapping
      experiments using the PISTILLATA or the full 35S promoter demonstrated that the
      LAS 3' enhancer also has suppressor functions, largely overwriting the activity
      of different 5' promoters. Phylogenetic analyses suggest that LAS function and
      regulation are evolutionarily highly conserved. Homologous elements in downstream
      regulatory sequences were found in all LAS orthologs, including grasses.
      Transcomplementation experiments demonstrated the functional conservation of non
      coding sequences between Solanum lycopersicum (tomato) and Arabidopsis. In
      summary, our results show that a highly conserved enhancer/suppressor element is
      the main regulatory module conferring the boundary-specific expression of LAS.

PMID- 21722221
TI  - The views of mental health nurses on continuing professional development.
AB  - AIMS AND OBJECTIVES: To determine clinical mental health nurses' views and
      preferences about continuing professional development. BACKGROUND: Participation
      in continuing professional development is now expected for nurse and midwifery
      registration. However, it is unclear how clinically based mental health nurses
      view continuing professional development and its relevance to career intentions.
      DESIGN: Qualitative. METHOD: Semi-structured face-to-face interviews with mental
      health nurses (n=50) drawn from inpatient mental health units. RESULTS: The most
      prominent factor identified through this research is that the majority of the
      fifty participants valued continuing professional development and sought more
      opportunities to participate. They particularly favoured in-house locally based
      sessions targeting patient-related clinical skills enhancement. Importantly, this
      interest in continuing professional development was not confined to new graduates
      needing to consolidate their skills. Work-based flexibility, the types of courses
      available and opportunities for study leave were also identified as important
      factors. Of the 50 nurses interviewed, 40% expressed a desire for continuing
      professional development vis-a-vis remaining in the service; 30% of nurses
      responded to the same question with an emphasis on the importance of collegial
      support amongst peers and management; and 30% of the nurses indicated their
      primary focus for continuing professional development was to further their
      tertiary studies. CONCLUSIONS: These results are not only timely given the
      requirements around continuing professional development, but are also important
      to drive improvements in quality continuing professional development where needs
      are prioritised, discussed and agreed on. RELEVANCE TO CLINICAL PRACTICE:
      Findings from this study highlight the value clinical nurses place on having
      access to work-based and clinically focussed education and development. Relevant
      on-the-job professional education has the potential to improve job satisfaction
      and retention of clinical nurses, thus ultimately directly and positively
      influence patient care.

PMID- 21722222
TI  - The evolution of the role of the Emergency Nurse Practitioner in Scotland: a
      longitudinal study.
AB  - AIMS AND OBJECTIVES: To examine how the role of the Emergency Nurse Practitioner
      has evolved in Scotland. BACKGROUND: In 2001, Cooper and colleagues published a
      report on their survey (carried out in 1998) which described the extent and
      nature of Emergency Nurse Practitioner services in Scotland. They described a
      nascent nursing role and service that existed in almost half of Emergency
      Departments and that concentrated its activity on the management of minor distal
      limb trauma and wound management. Since that date, several relevant and important
      political, professional and local issues have combined to accelerate the
      development of this role. DESIGN: Longitudinal survey of Scottish Emergency
      Departments (n = 97 in 1998, n = 93 in 2009). METHOD: Census survey of all
      Scottish Emergency Departments identified by NHS National Services Scotland's
      Information and Statistics Division Accident and Emergency Waiting Times dataset
      2006-07. RESULTS: Emergency Nurse Practitioners are now practising in the
      majority (89%) of Emergency Departments and Minor Injury Units compared with 47%
      in 1998. Most departments (78%) use Emergency Nurse Practitioners in dual roles,
      and most departments (67%) differentiate their Emergency Nurse Practitioners from
      other nursing staff by use of a title. Wide variations in pay, role and scope of
      practice still exist. CONCLUSIONS: The role of the Emergency Nurse Practitioner
      has increasingly become part of mainstream health care delivery in Emergency
      Departments across Scotland and can now be considered to be common place. This
      study demonstrates that 'Advanced Nursing Practitioners' and 'Nurse
      Practitioners' cannot necessarily be considered to be synonymous, and nursing
      roles that are allowed to evolve naturally adopt a non-uniform level of practice.
      RELEVANCE TO CLINICAL PRACTICE: This paper is of interest to Nurse Practitioners
      and workforce planners.

PMID- 21722223
TI  - Comparing quality of nutritional care in Dutch and German nursing homes.
AB  - AIMS AND OBJECTIVES: This study investigates possible differences in malnutrition
      prevalence rates in Dutch and German nursing homes. It seeks to provide insight
      into the screening, prevention and treatment of malnutrition and the indicators
      for nutritional care policy. BACKGROUND: For decades, malnutrition has been an
      important problem in health care settings worldwide. A considerable percentage of
      frail older people suffer from malnutrition. In European nursing homes, the
      reported prevalence rates range widely (2% to 85%). METHOD: This is a
      multicentre, cross-sectional prevalence study of malnutrition in Dutch and German
      nursing homes using standardised methodology, with the participation of
      respectively 5848 and 4923 residents (65+ years). RESULTS: Patient
      characteristics differed significantly between the two countries. Dutch residents
      were more often male, younger, more care-dependent and significantly more at risk
      of malnutrition (31.7%). However, overall malnutrition prevalence rates did not
      differ significantly (Netherlands 26.8% and Germany 26.5%). All German residents
      were screened at admission, whereas only 73.1% of the Dutch residents were. As
      part of screening, nutritional screening tools were used in 38.0% of Dutch and
      42.1% of the German residents. A dietician was consulted for 36.7% Dutch and 9.3%
      German malnourished residents. The proportion of malnourished receiving
      nutritional intervention was larger in Germany than in the Netherlands.
      Structural indicators for nutritional policy were fulfilled more often in the
      Netherlands care at institutional level whereas in Germany they were fulfilled
      more often at ward level. CONCLUSION: In this study, German residents had a
      somewhat better nutritional status than Dutch residents and more is done to
      enhance nutritional status in German nursing homes. The differences would be
      somewhat larger if both populations were more comparable. RELEVANCE TO CLINICAL
      PRACTICE: Comparing malnutrition prevalence rates, prevention and interventions
      in health care institutions and countries gives insight into international
      differences in quality of care.

PMID- 21722224
TI  - Measuring patient and visitor violence in general hospitals: feasibility of the
      SOVES-G-R, internal consistency and construct validity of the POAS-S and the
      POIS.
AB  - AIMS: To investigate the feasibility of a survey measuring patient and visitor
      violence after translation and modification, namely the Survey of Violence
      Experienced by Staff (German version revised) and to validate the shortened
      Perception of Aggression Scale (POAS-S) and the Perception of Importance of
      Intervention Skills Scale (POIS) after adaptation for use in a general hospital
      setting. BACKGROUND: The use of different approaches and research instruments for
      investigating patient and visitor violence negatively influences the
      comparability of studies. Typically, general hospitals use self-administered
      surveys. However, support for these instruments' validity is insufficient.
      METHODS: Between November 2006-January 2007, 291 nurses working in general
      hospitals in the German-speaking region of Switzerland completed the SOVES-G-R,
      the POAS-S and the POIS (response rate=71%). Results. The participants' responses
      demonstrated a need for modifications to enhance the feasibility of the SOVES-G-R
      in two categories, namely experiences with patient and visitor violence in 'the
      past 12 months' and in 'the past working week'. The POAS-S revealed the same
      factor solution as in earlier studies, with two factors explaining 38.0% of
      variance. In the POIS, two factors were distinguished: (1) structured
      interventions and evaluation and (2) the importance of preventive measures.
      CONCLUSIONS: The SOVES-G-R, the POAS-S and the POIS are adequate for
      investigating factors influencing the occurrence of patient and visitor violence
      in general hospitals. Given the changes in the SOVES-G-R and the moderate size of
      our sample, further testing with a larger sample is recommended. RELEVANCE TO
      CLINICAL PRACTICE: The instruments help determine which clinical settings have a
      greater risk of patient and visitor violence and the specific factors that
      influence this risk. This can facilitate the implementation of situation-specific
      preventive measures against patient and visitor violence in general hospitals.

PMID- 21722225
TI  - Reproductive strategies and population structure in Leishmania: substantial
      amount of sex in Leishmania Viannia guyanensis.
AB  - Leishmania species of the subgenus Viannia and especially Leishmania Viannia
      guyanensis are responsible for a large proportion of New World leishmaniasis
      cases. Since a recent publication on Leishmania Viannia braziliensis, the debate
      on the mode of reproduction of Leishmania parasites has been reopened. A
      predominant endogamic reproductive mode (mating with relatives), together with
      strong Wahlund effects (sampling of strains from heterogeneous subpopulations),
      was indeed evidenced. To determine whether this hypothesis can be generalized to
      other Leishmania Viannia species, we performed a population genetic study on 153
      human strains of L. (V.) guyanensis from French Guiana based on 12 microsatellite
      loci. The results revealed important homozygosity and very modest linkage
      disequilibrium, which is in agreement with a high level of sexual recombination
      and substantial endogamy. These results also revealed a significant isolation by
      distance with relatively small neighbourhoods and hence substantial viscosity of
      Leishmania populations in French Guiana. These results are of epidemiological
      relevance and suggest a major role for natural hosts and/or vectors in parasite
      strain diffusion across the country as compared to human hosts.

PMID- 21722226
TI  - Interploidal hybridization and mating patterns in the Sphagnum subsecundum
      complex.
AB  - Polyploidization is thought to result in instant sympatric speciation, but
      several cases of hybrid zones between one of the parental species and its
      polyploid derivative have been documented. Previous work showed that diploid
      Sphagnum lescurii is an allopolyploid derived from the haploids S. lescurii
      (maternal progenitor) and S. subsecundum (paternal progenitor). Here, we report
      the results from analyses of a population where allodiploid and haploid S.
      lescurii co-occur and produce sporophytes. We tested (i) whether haploids and
      diploids form hybrid triploid sporophytes; (ii) how hybrid and nonhybrid
      sporophytes compare in fitness; (iii) whether hybrid sporophytes form viable
      spores; (iv) the ploidy of any viable gametophyte offspring from hybrid
      sporophytes; (v) the relative viability of sporelings derived from hybrid and
      nonhybrid sporophytes; and (vi) if interploidal hybridization results in
      introgression between the allopolyploid and its haploid progenitor. We found that
      triploid hybrid sporophytes do occur and are larger than nonhybrid sporophytes,
      but exhibit very low germination percentages and produce sporelings that develop
      more slowly than those from nonhybrid sporophytes. All sporophytes attached to
      haploid gametophytes were triploid and were sired by diploid males, but all
      sporophytes attached to diploid gametophytes were tetraploid. This asymmetric
      pattern of interploidal hybridization is related to an absence of haploid male
      gametophytes in the population. Surprisingly, all sporelings from triploid
      sporophytes were triploid, yet were genetically variable, suggesting some form of
      aberrant meiosis that warrants further study. There was limited (but some)
      evidence of introgression between allodiploid and haploid S. lescurii.

PMID- 21722227
TI  - Pro con debate: the use of regional vs systemic analgesia for neonatal surgery.
AB  - In recent years the inclusion of regional techniques to pediatric anesthesia has
      transformed practice. Simple procedures such as caudal anesthesia with local
      anaesthetics can reduce the amounts of general anesthesia required and provide
      complete analgesia in the postoperative period while avoiding large amounts of
      opioid analgesia with potential side effects that can impair recovery. However,
      the application of central blocks (epidural and spinal local anesthesia) via
      catheters in the younger infant, neonate and even preterm neonate remains more
      controversial. The potential for such invasive maneuvers themselves to augment
      risk, can be argued to outweigh the benefits, others would argue that epidural
      analgesia can reduce the need for postoperative ventilation and that this not
      only facilitates surgery when intensive care facilities are limited, but also
      reduces cost in terms of PICU stay and recovery profile. Currently, opinions are
      divided and strongly held with some major units adopting this approach widely and
      others maintaining a more conservative stance to anesthesia for major neonatal
      surgery. In this pro-con debate the evidence base is examined, supplemented with
      expert opinion to try to provide a balanced overall view.

PMID- 21722228
TI  - Explaining the acetaminophen-ibuprofen analgesic interaction using a response
      surface model.
AB  - BACKGROUND: The value of acetaminophen-ibuprofen combination therapy over single
      therapy is uncertain in acute pediatric pain management. A model describing the
      interaction between these two drugs would be useful both for understanding
      current literature and for future study design. METHODS: Published pooled time
      effect profiles in adults given combination or single therapy after dental
      extraction were used to construct an interaction model. Pain was measured using
      pain intensity differences (PRID, 0-10) from zero to eight hours postoperatively.
      Pharmacodynamic parameter estimates were assumed the same in adults as children.
      Pediatric pharmacokinetic estimates were scaled using allometric theory. Curve
      fitting was performed using nonlinear mixed effects models. RESULTS: Pooled data
      were available in adults given eight single and multiple dose combinations as
      well as placebo. The ibuprofen dose range was 100-400 mg, and acetaminophen dose
      range was 500-1000 mg. Pharmacodynamic parameter estimates, expressed using the
      Hill equation, were maximum effect (E(MAX) ) 4.06 (95% CI: 3.24, 5.51), the
      concentration of acetaminophen associated with 50% of the maximal drug effect
      (EC(50,ACET) ) 11.9 (95% CI: 6.0, 49.5) mg.l(-1) , the ibuprofen EC(50)
      (EC(50,IBU) ) 5.07 (95% CI: 3.50, 8.26) mg.l(-1), and Hill coefficient 2 (95% CI:
      1.3, 2.8). An interaction term was fixed at zero (additive interaction).
      Simulation showed that the addition of acetaminophen to ibuprofen when less than
      5 mg.kg(-1) was effective; acetaminophen had minimal effect when given with
      ibuprofen at doses greater than 5 mg.kg(-1) in the immediate postoperative
      period. A more sustained analgesic effect was noted at 4-8 h after combination
      dosing. CONCLUSIONS: This drug interaction modeling example is useful to explain
      combination therapy nuances and impacts on study design. Differences in effect
      between single drug therapy and combination therapy should be sought at lower
      doses and beyond the immediate postoperative period. Combination therapy may
      prolong the duration of analgesia. The maximum effect (E(MAX) ) limits the early
      additional analgesic gain from combination therapy beyond commonly used doses.

PMID- 21722229
TI  - Retraction. Controversial issues: compartment syndrome, test dose, LOR-
      air/saline, etc.

PMID- 21722230
TI  - Excess comorbidities associated with malignant hyperthermia diagnosis in
      pediatric hospital discharge records.
AB  - BACKGROUND: Case reports have linked malignant hyperthermia (MH) to several
      genetic diseases. OBJECTIVE/AIM: The objective of this study was to
      quantitatively assess excess comorbidities associated with MH diagnosis in
      pediatric hospital discharge records. PATIENTS AND METHODS: Data for this study
      came from the Kids' Inpatient Database (KID) for the years 2000, 2003, and 2006.
      The KID contains an 80% random sample of patients under the age of 21 discharged
      from short-term, non-Federal hospitals in the United States, with up to 19
      diagnoses recorded for each patient. Using all pediatric inpatients as the
      reference, we calculated the standardized morbidity ratios (SMRs) and 95%
      confidence intervals (CIs) for children with MH diagnosis according to major
      disease groups and specific medical conditions. RESULTS: Of the 5,916,989
      nonbirth-related hospital discharges studied, 175 had a recorded diagnosis of MH.
      Compared with the general pediatric inpatient population, children with MH
      diagnosis were significantly more likely to be diagnosed with diseases of the
      musculoskeletal system and connective tissue (SMR 5.7; 95% CI: 3.9-7.9), diseases
      of the circulatory system (SMR 3.3; 95% CI: 2.1-4.8), and congenital anomalies
      (SMR 3.2; 95% CI: 2.3-4.4). The specific diagnosis that was most strongly
      associated with MH was muscular dystrophies (SMR 31.3; 95% CI 12.6-64.6).
      CONCLUSIONS: Diseases of the musculoskeletal system and connective tissue are
      significantly associated with MH diagnosis in children. Further research is
      warranted to determine the clinical utility of these comorbidities in assessing
      MH susceptibility in children.

PMID- 21722231
TI  - Implementation of automated external defibrillators on German merchant ships.

PMID- 21722232
TI  - The potential utility of adjuvanted seasonal influenza vaccine for travelers.

PMID- 21722233
TI  - Implementation of automated external defibrillators on merchant ships.
AB  - BACKGROUND: In contrast to cruise ships, ferries and merchant ships are rarely
      equipped with automated external defibrillators (AEDs). Germany is the first flag
      state worldwide that legally requires to carry AEDs on seagoing merchant vessels
      by September 2012 at the latest. OBJECTIVES: The aim of this study was to
      investigate the effect of training ship officers in the handling of AEDs and to
      explore their perceptions concerning the user-friendliness of currently available
      defibrillators. METHODS: Using four different AEDs, 130 nautical officers
      performed a total of 400 resuscitation drills. One group (n = 60) used only one
      device before and after resuscitation training; the other group (n = 70) used all
      four AEDs in comparison after training. The officers' performances were timed and
      they were asked by questionnaire about the user-friendliness of each AED.
      RESULTS: Without resuscitation training, 81.7% of the first mentioned group
      delivered an effective defibrillation shock. After a 7-hour resuscitation
      training with special regard to defibrillation, all ship officers (n = 130) used
      the AED correctly. Among all AEDs, the mean time until start of analysis
      decreased from 72.4 seconds before to 60.4 seconds after resuscitation training
      (Wilcoxon test; p < 0.001). The results of the questionnaire and the differences
      in time to first shock indicated a different user-friendliness of the AEDs. The
      voice prompts and the screen messages of all AEDs were well understood by all
      participants. In the second mentioned group, 57.1% regarded feedback information
      related to depths and frequency of thorax compression as helpful. CONCLUSION:
      Nautical officers are able to use AEDs in a timely and effective way with proper
      training. However, to take advantage of all wanted features of the device
      (monitoring and resuscitation), the ship management has to observe practical
      questions of storage, maintenance, signing, training, data management, and
      transmission. Thus, implementation of the regulations requires proper
      instructions for the maritime industry by responsible bodies.

PMID- 21722234
TI  - Fever in travelers returning from malaria-endemic areas: don't look for malaria
      only.
AB  - BACKGROUND: Returning travelers with fever pose challenges for clinicians because
      of the multitude of diagnostic alternatives. Case data in a Finnish tertiary
      hospital were analyzed in order to define the causes of fever in returned
      travelers and to evaluate the current diagnostic approach. METHODS: A
      retrospective study of patient records comprised 462 febrile adults who, after
      traveling in malaria-endemic areas, were admitted to the Helsinki University
      Central Hospital (HUCH) emergency room from 2005 to 2009. These patients were
      identified through requests for malaria smear. RESULTS: The most common groups of
      diagnoses were acute diarrheal disease (126 patients/27%), systemic febrile
      illness (95/21%), and respiratory illness (69/15%). The most common specific main
      diagnosis was Campylobacter infection (40/9%). Malaria was diagnosed in 4%
      (20/462). Blood culture was positive for bacteria in 5% of those tested (21/428).
      Eight patients were diagnosed with influenza. HIV-antibodies were tested in 174
      patients (38%) and proved positive in 3% of them (5/174, 1% of all patients). The
      cause of fever was noninfectious in 12 (3%), remaining unknown in 116 (25%).
      Potentially life-threatening illnesses were diagnosed in 118 patients (26%), the
      strongest risk factors were baseline C-reactive protein (CRP) >=100 (OR 3.6; 95%
      CI 2.0-6.4) and platelet count <=140 (OR 3.8; 95% CI 2.0-7.3). Nine patients (2%)
      were treated in high dependency or intensive care units; one died of septicemia.
      Forty-five patients (10%) had more than one diagnosis. CONCLUSION: The high
      proportion of patients with more than one diagnosis proves the importance of
      careful diagnostics. Every fourth returning traveler with fever had a potentially
      life-threatening illness. Septicemia was as common as malaria. The proportion of
      HIV cases exceeded the prevalence in population for which Centers for Disease
      Control and Prevention, USA (CDC) recommends routine HIV testing. Both blood
      cultures and HIV tests should be considered in febrile travelers.

PMID- 21722235
TI  - Choice of and adherence to prophylactic antimalarials.
AB  - BACKGROUND: There were 1,370 cases of imported malaria and six fatalities in the
      UK in 2008, the majority of which were due to chloroquine-resistant Plasmodium
      falciparum. Poor adherence to prescribed regimens is known to be an important
      factor in these cases. METHOD: An observational study utilizing questionnaires
      both pre- and post-travel was conducted to assess the adherence behavior of UK
      travelers undertaking trips of less than 28 days duration, who were prescribed
      one of three antimalarials recommended to prevent P falciparum malaria
      (atovaquone plus proguanil, doxycycline, or mefloquine) in travel clinics in
      England and Scotland. The primary objectives of the study were to assess
      travelers' perceptions of, and self-reported adherence to antimalarial
      medication. A secondary objective was to examine the reasons for the choice of
      antimalarial therapy from the perspective of prescriber and traveler. RESULTS:
      For the primary end point of self-reported adherence specified as the proportion
      of antimalarial tablets prescribed that were actually taken, statistically
      significantly higher adherence overall and post-travel was seen with atovaquone
      plus proguanil compared with doxycycline. It was not possible to calculate the
      statistical significance of comparisons with mefloquine, but adherence to
      mefloquine appeared similar to or better than doxycycline and similar to
      atovaquone plus proguanil for categorical adherence. Effectiveness, side effects,
      previous experience of antimalarials, and dosing convenience were the main
      determinants of both travelers and practitioner's choice of antimalarial. The
      practitioner's recommendation was highly important for 63% of travelers.
      CONCLUSION: A shorter post-travel regimen has a significant impact on adherence
      to antimalarial prophylaxis. A reassessment of the risk by travelers on returning
      home may be a major contributor to this poor adherence.

PMID- 21722236
TI  - Irritable bowel syndrome among a cohort of European travelers to resource-limited
      destinations.
AB  - BACKGROUND: Travelers' diarrhea (TD) remains a frequent travel-associated
      infection. Between 4 and 32% of enteric infections were followed by a
      postinfectious irritable bowel syndrome (pIBS) with long-term sequelae in various
      settings. Travel-related IBS incidence rates are based on small studies and IBS
      predictors have not been sufficiently evaluated. METHODS: Adult travelers to
      resource-limited destinations participated in a prospective questionnaire-based
      cohort study. Demographics, travel characteristics, and medical history were
      assessed and those with functional or organic gastrointestinal disorders were
      excluded. Immediately after return from abroad, the volunteers completed a second
      questionnaire on TD, other health impairments, and on nutritional hygiene. Six
      months post-travel, a follow-up questionnaire assessed IBS based on Rome III
      criteria. Risk factors were analyzed by multiple logistic regression. RESULTS:
      Among a total of 2,476 subjects analyzed (participation rate 72.4%), 38 (1.5%)
      developed new IBS, and the 6-month incidence rate for pIBS was 3.0% (95% CI 1.9
      4.2) following TD. Significant risk factors were TD during the surveyed journey
      (OR 3.7; 95% 1.8-7.4), an adverse life event experienced within 12 months pre
      travel (OR 3.1; 1.4-6.8), and a diarrheal episode experienced within 4 months pre
      travel (OR 2.7; 95% CI 1.3-5.6). Following multiple diarrheal episodes, the risk
      of acquiring IBS increased by six times. CONCLUSIONS: In a large population of
      European travelers IBS had a lower incidence rate as compared to previous
      studies. Particular risk groups were identified; those may need to be protected.

PMID- 21722237
TI  - Rabies postexposure prophylaxis in a UK travel clinic: ten years' experience.
AB  - BACKGROUND: In 2009, 58.6 million UK residents traveled abroad. Of these, 49.5
      million (84.5%) visits were to Europe and North America and 9.1 million (15.5%)
      were to other parts of the world. Rabies is widely distributed and continues to
      be a major public health issue in many developing countries. The UK is free of
      rabies in carnivore host species, although cases of rabies in bats have been
      reported. This study examined the rabies postexposure prophylaxis (PEP) service
      from 2000 to July 2009 at the Liverpool School of Tropical Medicine. METHODS:
      Medical records of patients who attended the clinic for rabies PEP were reviewed.
      RESULTS: During the study period, 139 patients were treated for possible rabies
      exposure. The mean age was 35 years. Thailand and Turkey each accounted for 31
      (22.3%) cases. Sixty-nine (49.6%) of those seen were due to dog bites. Most
      injuries involved a lower limb (n = 67, 48.2%) or hands (n = 26, 18.7%). Eighty
      six (61.9%) cases had initiated rabies PEP overseas, but only 3 of the 78 (3.8%)
      meeting UK criteria for rabies immunoglobulin (RIG) received it while overseas.
      Only an additional 11 patients received RIG on return to the UK; most were seen
      more than 7 days after initiation of PEP. The median time from exposure to
      receiving rabies PEP was 1 day (range: 0-1,720). Only 14 (10.1%) had received
      preexposure rabies vaccination. CONCLUSIONS: The majority of travelers seeking
      PEP at this clinic initiated treatment overseas. Most had not received RIG
      abroad, when it would have been appropriate. Initiation of appropriate treatment
      is often delayed and is a concern to those without preexposure rabies
      immunization. In view of the scarcity of RIG, travelers need to be aware of the
      risks, consider preexposure immunization, and present early for PEP.

PMID- 21722238
TI  - Development and validation of an instrument to assess the risk of developing
      viral infections in Australian travelers during international travel.
AB  - BACKGROUND: Questionnaires are widely used for data collection in travel medicine
      studies, but there are no validated instruments that are available to researchers
      in this field. Our objective was to develop and validate a questionnaire to be
      used in a prospective study designed to estimate the risk of three viral
      infections in Australian travelers to Asia. METHODS: Qualitative nonexperimental
      cognitive methods, including cognitive review, task analysis, and cognitive
      interviews, were selected. A pilot study was performed to assess the instrument
      in the target population. RESULTS: Recalling dates related to travel or health
      events was observed and reported to be the most difficult task for travelers. The
      use of cues embedded into items and provision of memory prompts such as calendars
      improves the recall of dates during travel. There is a wide spectrum of
      accommodation, activities, and travel experiences, and item responses that were
      constructed as lists were useful as memory triggers, particularly for travelers
      with long and complicated itineraries. Cognitive interviews provided a valuable
      insight into how travelers used inferential and direct memory to recall travel
      events and their confidence in the accuracy of these processes. CONCLUSIONS: The
      development and validation of questionnaires improve the accuracy of the data
      collected and should be considered an integral part of the methodology of travel
      related studies.

PMID- 21722239
TI  - General physicians do not take adequate travel histories.
AB  - BACKGROUND: Our aim was to document how often travel histories were taken and the
      quality of their content. METHODS: Patients admitted over 2 months to acute
      medical units of two hospitals in the Northwest of England with a history of
      fever, rash, diarrhea, vomiting, jaundice, or presenting as "unwell post-travel"
      were identified. The initial medical clerking was assessed. RESULTS: A total of
      132 relevant admissions were identified. A travel history was documented in only
      26 patients (19.7%). Of the 16 patients who had traveled, there was no
      documentation of pretravel advice or of sexual/other activities abroad in 15
      (93.8%) and 12 (75.0%) patients, respectively. CONCLUSIONS: There needs to be
      better awareness and education about travel-related illness and the importance of
      taking an adequate travel history.

PMID- 21722240
TI  - Fatal and severe box jellyfish stings, including Irukandji stings, in Malaysia,
      2000-2010.
AB  - BACKGROUND: Jellyfish are a common cause of injury throughout the world, with
      fatalities and severe systemic events not uncommon after tropical stings. The
      internet is a recent innovation to gain information on real-time health issues of
      travel destinations, including Southeast Asia. METHODS: We applied the model of
      internet-based retrospective health data aggregation, through the Divers Alert
      Network Asia-Pacific (DAN AP), together with more conventional methods of
      literature and media searches, to document the health significance, and clinical
      spectrum, of box jellyfish stings in Malaysia for the period January 1, 2000 to
      July 30, 2010. RESULTS: Three fatalities, consistent with chirodropid
      envenomation, were identified for the period-all tourists to Malaysia. Non-fatal
      chirodropid stings were also documented. During 2010, seven cases consistent with
      moderately severe Irukandji syndrome were reported to DAN and two representative
      cases are discussed here. Photographs of chirodropid (multi-tentacled), carybdeid
      (four-tentacled) box jellyfish, and of severe sting lesions were also submitted
      to DAN during this period. CONCLUSIONS: This study suggests that the frequency
      and severity of jellyfish stings affecting tourists in Southeast Asia have been
      significantly underestimated. Severe and fatal cases of chirodropid-type stings
      occur in coastal waters off Peninsular Malaysia and Sabah, Borneo. Indeed, the
      first Malaysian cases consistent with Irukandji-like syndrome are reported here.
      Reports to DAN, a provider of emergency advice to divers, offer one method to
      address the historic lack of formalized reporting mechanisms for such events, for
      photo-documentation of the possible culprit species and treatment advice. The
      application of marine stinger prevention and treatment principles throughout the
      region may help reduce the incidence and severity of such stings. Meanwhile
      travelers and their medical advisors should be aware of the hazards of these
      stings throughout the Asia-Pacific.

PMID- 21722241
TI  - Advice to travelers on topical insect repellent use against dengue mosquitoes in
      Far North Queensland, Australia.
AB  - Dengue outbreaks occur annually in Far North Queensland, Australia. Advice on
      topical insect repellents provided by health authorities rarely addresses the
      wide range of formulations and active ingredients currently registered for use in
      Australia. Recommendations on the use of registered products require review.

PMID- 21722242
TI  - Isolated intradural-extramedullary spinal cysticercosis: a case report.
AB  - Spinal cysticercosis is an uncommon manifestation of neurocysticercosis (NCC). We
      present a case of isolated lumbar intradural-extramedullary NCC. The patient was
      treated successfully with the surgical removal of the cyst. Spinal NCC should be
      considered in the differential diagnosis in high-risk populations with new
      symptoms suggestive of a spinal mass lesion.

PMID- 21722243
TI  - Nephrotic syndrome and unrecognized Plasmodium malariae infection in a US Navy
      sailor 14 years after departing Nigeria.
AB  - A 34-year-old Nigerian man presented with nephrotic syndrome. Renal biopsy
      revealed chronic membranous glomerulopathy with focal segmental sclerosis. Blood
      Giemsa smear contained rare Plasmodium sp. trophozoites and small subunit
      ribosomal RNA polymerase chain reaction amplification confirmed the presence of
      Plasmodium malariae. This case highlights the importance of obtaining even remote
      travel histories from ill immigrants and considering occult quartan malaria in
      patients from endemic locations with nephrotic syndrome.

PMID- 21722245
TI  - Travel medicine research priorities: establishing an evidence base.

PMID- 21722247
TI  - Cystic splenomegaly.

PMID- 21722248
TI  - Acinetobacter baumannii resistant to everything: what should we do?

PMID- 21722249
TI  - Treatment of typhoid fever in the 21st century: promises and shortcomings.
AB  - Emergence of multidrug resistance and decreased ciprofloxacin susceptibility
      (DCS) in Salmonella enterica serovar Typhi in South Asia have rendered older
      drugs, including ampicillin, chloramphenicol, trimethoprim-sulphamethoxazole,
      ciprofloxacin, and ofloxacin, ineffective or suboptimal for typhoid fever.
      Ideally, treatment should be safe and available for adults and children in
      shortened courses of 5 days, cause defervescence within 1 week, render blood and
      stool cultures sterile, and prevent relapse. In this review of 20 prospective
      clinical trials that enrolled more than 1600 culture-proven patients,
      azithromycin meets these criteria better than other drugs. Among
      fluoroquinolones, which are more effective than cephalosporins, gatifloxacin
      appears to be more effective than ciprofloxacin and ofloxacin for patients
      infected with bacteria showing DCS. Ceftriaxone continues to be useful as a back
      up choice, and chloramphenicol, despite its toxicity for bone marrow and history
      of plasmid-mediated resistance, is making a comeback in developing countries that
      show their bacteria to be susceptible to it.

PMID- 21722250
TI  - Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a
      relatively minor public health threat for Africa.
AB  - Ebola and Marburg viruses are the only members of the Filoviridae family (order
      Mononegavirales), a group of viruses characterized by a linear, non-segmented,
      single-strand negative RNA genome. They are among the most virulent pathogens for
      humans and great apes, causing acute haemorrhagic fever and death within a matter
      of days. Since their discovery 50 years ago, filoviruses have caused only a few
      outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is
      negligible compared with the devastation caused by malnutrition and other
      infectious diseases prevalent in Africa (malaria, cholera, AIDS, dengue,
      tuberculosis ...). Yet considerable human and financial resourses have been
      devoted to research on these viruses during the past two decades, partly because
      of their potential use as bioweapons. As a result, our understanding of the
      ecology, host interactions, and control of these viruses has improved
      considerably.

PMID- 21722251
TI  - Filariasis in Africa--treatment challenges and prospects.
AB  - Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections
      that are responsible for a major disease burden in the African continent. Disease
      symptoms are induced by the immune reactions of the host, with lymphoedema and
      hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis.
      Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and
      onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria,
      which cause a major part of the inflammation leading to symptoms and are
      antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin
      and albendazole are used in mass drug administration programmes, with the aim of
      interrupting transmission, with a consequent reduction in the burden of infection
      and, in some situations, leading to regional elimination of LF and
      onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an
      impediment to mass drug administration with ivermectin and albendazole, owing to
      the risk of encephalopathy being encountered upon administration of ivermectin.
      Research into new treatment options is exploring several improved delivery
      strategies for the classic drugs or new antibiotic treatment regimens for anti
      wolbachial chemotherapy.

PMID- 21722252
TI  - Sleeping sickness.
AB  - Human African trypanosomiasis (HAT), or sleeping sickness, is a vector-borne
      disease that flourishes in impoverished, rural parts of sub-Saharan Africa. It is
      caused by infection with the protozoan parasite Trypanosoma brucei and is
      transmitted by tsetse flies of the genus Glossina. The majority of cases are
      caused by T. b. gambiense, which gives rise to the chronic, anthroponotic endemic
      disease in Western and Central Africa. Infection with T. b. rhodesiense leads to
      the acute, zoonotic form of Eastern and Southern Africa. The parasites live and
      multiply extracellularly in the blood and tissue fluids of their human host. They
      have elaborated a variety of strategies for invading hosts, to escape the immune
      system and to take advantage of host growth factors. HAT is a challenging and
      deadly disease owing to its complex epidemiology and clinical presentation and,
      if left untreated, can result in high death rates. As one of the most neglected
      tropical diseases, HAT is characterized by the limited availability of safe and
      cost-effective control tools. No vaccine against HAT is available, and the
      toxicity of existing old and cumbersome drugs precludes the adoption of control
      strategies based on preventive chemotherapy. As a result, the keystones of
      interventions against sleeping sickness are active and passive case-finding for
      early detection of cases followed by treatment, vector control and animal
      reservoir management. New methods to diagnose and treat patients and to control
      transmission by the tsetse fly are needed to achieve the goal of global
      elimination of the disease.

PMID- 21722253
TI  - Rickettsia felis: from a rare disease in the USA to a common cause of fever in
      sub-Saharan Africa.
AB  - Rickettsia felis is a spotted fever group rickettsia that has been definitely
      described in 2002. Within the last 20 years, there have been a growing number of
      reports implicating R. felis as a human pathogen, parallel to the fast-growing
      reports of the worldwide detection of R. felis in arthropod hosts, mainly the cat
      flea Ctenocephalides felis felis. R. felis is now known as the agent of the so
      called flea-borne spotted fever, with more than 70 cases documented in the
      literature. Recently, two studies respectively conducted in Senegal and Kenya,
      have challenged the importance of R. felis infection in patients with unexplained
      fever in sub-Saharan Africa. We focus here on the epidemiological and clinical
      aspects of R. felis infection. More studies are needed, including the study of
      other arthropod vectors, but it can be speculated that R. felis infection might
      be an important neglected agent of fever in sub-Saharan Africa.

PMID- 21722254
TI  - A novel complex class 1 integron found in a Klebsiella pneumoniae isolate from
      Portugal.
AB  - Klebsiella pneumoniae Kp1 carrying a novel complex class 1 integron was isolated
      from an inanimate surface of a female ward sanitary facility in the Hospital
      Infante D. Pedro, Aveiro, central Portugal. The integron consists of two variable
      regions (VRs); VR1 was previously described in Escherichia coli and Vibrio
      cholerae, and VR2 contains an In37-like structure and is located downstream of an
      ISCR1 element. The integron was found on a plasmid of 225 kb. The qnrB10 gene,
      although present, is not associated with the complex class 1 integron.

PMID- 21722255
TI  - Molecular characteristics of extended-spectrum beta-lactamase-producing
      Escherichia coli from Rio de Janeiro, Brazil.
AB  - Twenty-five extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli
      clinical isolates from Rio de Janeiro, Brazil were characterized by isoelectric
      focusing, PCR and sequencing of bla(ESBL) genes, plasmid-mediated quinolone
      resistance determinants, phylogenetic groups, replicon typing, pulsed-field
      electrophoresis, and multilocus sequencing typing. Twenty-three (92%) ESBL
      producing E. coli isolates were positive for bla(CTX-M) genes, aac(6')-Ib-cr, and
      qnrB. Genetic relatedness of ESBL producers clustered seven (28%) CTX-M-15
      producing isolates as sequence type (ST)410, clonal complex (CC) 23, and two (8%)
      as clone O25-ST131. Our results illustrate the predominance of phylogroup A
      (52%), ST410 (CC 23) and CTX-M-15 among ESBL-producing E. coli isolates from
      hospitals in Rio de Janeiro.

PMID- 21722256
TI  - Phenotypic identification of over 1000 isolates of anaerobic bacteria recovered
      between 1999 and 2008 in a major Costa Rican hospital.
AB  - Because of limitations in infrastructure, the aetiology of infections caused by
      anaerobic bacteria is seldom determined in clinical laboratories of developing
      countries. This study reports on the identification of 1010 anaerobic bacterial
      isolates collected between 1999 and 2008 in a major Costa Rican hospital with the
      use of two commercial phenotypic systems (RapID 32A and API 20A). Approximately
      60% of the isolates were Gram-positive and, among the 35 species of Gram-positive
      bacteria found, the genera Clostridium, Propionibacterium and Eggerthella, and
      anaerobic cocci predominated. Twenty eight species were found among 395 isolates
      of Gram-negative bacteria. Species of Bacteroides were very frequent, followed by
      species of Prevotella, Veillonella, Fusobacterium and Porphyromonas.

PMID- 21722257
TI  - Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections.
AB  - The aim of this study was to evaluate the impact of carbapenem-resistant K.
      pneumoniae bloodstream infections on mortality. During the study period 42, 68
      and 120 patients were identified with carbapenem-resistant, extended-spectrum
      beta-lactamase producers (ESBL) and susceptible K. pneumoniae bloodstream
      infections, respectively. Patients with carbapenem-resistant K. pneumoniae had
      higher rates of prior antimicrobial exposure, other nosocomial infections, and
      use of invasive devices. Infection-related mortality was 48% for carbapenem
      resistant, 22% for ESBL producers and 17% for susceptible K. pneumoniae.
      Independent risk factors for infection-related mortality were Pitt bacteraemia
      score, Charlson score and carbapenem resistance.

PMID- 21722258
TI  - Invasive neonatal GBS infections from an area-based surveillance study in Italy.
AB  - During an area-based study, 75 group B streptococcus (GBS) strains isolated both
      from early-onset disease (EOD, 37 strains) and from late-onset disease (LOD, 38
      strains) were analysed for serotype, pulsed field gel electrophoresis (PFGE) and
      multilocus sequence typing profiles, protein markers and antibiotic resistance.
      Serotype III, possessing the rib gene, was the most frequent (54 strains, 72%)
      and responsible for 89.5% and 54% of LOD and EOD, respectively. Forty-six
      serotype III strains belonged to the same PFGE type and clonal complex 17,
      already described as an over-represented clone in neonatal invasive GBS
      infections. Other serotypes were Ia (9.3%), II (6.7%), Ib (5.3%), V (5.3%) and IV
      (1.3%). Seventeen PFGE groups were identified comprising strains with related
      sequence types; conversely, strains displaying the same sequence type could
      belong to different PFGE groups. When both neonate and maternal strains from
      vaginorectal swabs and/or milk were available (eight cases), they were
      indistinguishable. Resistance to erythromycin (12%) was associated with a
      constitutive resistance to clindamycin in five cases (four carrying the erm(B)
      gene and one both the erm(B) and mef(E) genes) and with an inducible clindamycin
      resistance in two cases (one possessing the erm(A) gene, the other the erm(T)
      gene). Two isolates displayed the M phenotype (mef(E) gene). All strains but five
      were resistant to tetracycline, mostly mediated by the tet(M) gene (97.1%). The
      study underlined the importance of an active surveillance system for the
      elucidation of a GBS population structure causing neonatal infections and allowed
      the detection of rare antibiotic resistance determinants [erm(T)].

PMID- 21722259
TI  - Klebsiella pneumoniae: development of a mixed population of carbapenem and
      tigecycline resistance during antimicrobial therapy in a kidney transplant
      patient.
AB  - Nine isolates of Klebsiella pneumoniae were isolated from a renal transplant
      patient suffering from recurrent urosepsis over a period of 4 months. Imipenem
      resistance was detected after imipenem-ertapenem therapy. When treatment was
      switched to tigecycline the K. pneumoniae developed resistance to tigecycline
      (MIC = 8 mg/L). The nine isolates were tested by determination of agar dilution
      MICs, phenotypic carbapenemase, extended-spectrum beta-lactamases and metallo
      beta-lactamase (MBL) testing and pulsed-field gel electrophoresis. Polymerase
      chain reaction and sequencing analysis were employed for identification of bla
      genes and mapping of the integron carrying the MBL gene. The nine isolates were
      clonally related and all produced the SHV-12 enzyme. Five MBL-producing isolates
      showed imipenem MICs ranging from 2 to 64 mg/L and all were detected by testing
      with imipenem and EDTA. The five isolates harboured the bla(VIM-1) gene. Three
      isolates showed increased tigecycline MICs (4-8 mg/L). Serial blood cultures
      obtained on the same day resulted in a VIM-positive/tigecycline-susceptible and a
      VIM-negative/tigecycline-resistant K. pneumoniae isolate. No isolate developed
      concurrent imipenem and tigecycline resistance. The patient had a persistent
      urinary tract infection and recurrent bacteraemia caused by a mixed population of
      Klebesiella pneumoniae isolates adapting to the selective pressure of
      antimicrobial therapy at the time. The present study is a worrisome example of
      what could happen when an immunocompromised host is subjected to the pressures of
      antimicrobial therapy. In addition, we report the first treatment-emergent MIC
      increase of tigecycline from 0.5 to 8 mg/L in K. pneumoniae.

PMID- 21722260
TI  - Clinical relevance of cagA and vacA gene polymorphisms in Helicobacter pylori
      isolates from Senegalese patients.
AB  - The molecular epidemiology of Helicobacter pylori in Africa is poorly documented.
      From January 2007 to December 2008, we investigated 187 patients with gastric
      symptoms in one of the main tertiary hospitals in Dakar, Senegal. One hundred and
      seventeen patients were culture-positive for H. pylori. Polymorphisms in vacA and
      cagA status were investigated by PCR; the 3'-region of cagA was sequenced, and
      EPIYA motifs were identified. Bacterial heterogeneity within individuals was
      extensively assessed by using an approach based on vacA and cagA heterogeneity.
      Fourteen per cent of H. pylori-positive patients displayed evidence of mixed
      infection, which may affect disease outcome. Patients with multiple vacA alleles
      were excluded from subsequent analyses. Among the final study population of 105
      patients, 29 had gastritis only, 61 had ulcerated lesions, and 15 had suspicion
      of neoplasia based on endoscopic findings. All cases of suspected neoplasia were
      histologically confirmed as gastric cancer (GC). The cagA gene was present in
      73.3% of isolates. CagA proteins contained zero (3.7%), one (93.9%) or two (2.4%)
      EPIYA-C segments, and all were western CagA. Most of the isolates possessed
      presumed high-vacuolization isotypes (s1i1m1 (57.1%) or s1i1m2 (21.9%)). Despite
      the small number of cases, GC was associated with cagA (p 0.03), two EPIYA-C
      segments in the C-terminal region of CagA (p 0.03), and the s1 vacA allele (p
      0.002). Multiple EPIYA-C segments were less frequent than reported in other
      countries, possibly contributing to the low incidence of GC in Senegal.

PMID- 21722261
TI  - Epidemiological characterization and distribution of carbapenem-resistant
      Acinetobacter baumannii clinical isolates in Italy.
AB  - This study was aimed at tracing the molecular characteristics of carbapenem
      resistant Acinetobacter baumannii (CRAB) clinical isolates in Italy with both
      pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).
      Two hundred and two CRAB isolates were collected during 2004-2009, in two
      different surveillance periods, from 22 Italian hospitals that were
      representative for both distribution and infection. PFGE was performed, and the
      MLST scheme used was based on the gene sequence as published on the MLST Pasteur
      website http://www.pasteur.fr/mlst. Representatives of the major European clones
      I (RUH 875) and II (RUH 134) were used as controls. The two groups of isolates
      were characterized for their carbapenem resistance genes: 154 of 202 carried
      bla(OXA-58) alone, 21 of 202 also carried bla(OXA-23) , and 27 of 202 carried
      bla(OXA-23) alone. No isolates were positive for bla(OXA-24) . Genotype analysis
      of all isolates identified four distinct patterns by PFGE, which correlated with
      four distinct sequence types (STs) by MLST. The distribution of these four
      clusters in Italy confirmed the propensity of A. baumannii for nosocomial cross
      transmission in a vast geographical area. We observed that clones A and B had
      similarities with European clone II and I respectively. By MLST, clone A was ST2,
      like European clone II, and clone B was ST1, like European clone I. PFGE and MLST
      showed the same discriminatory power and reproducibility. In addition, the two
      methods were concordant in defining CRAB Italian clones and in correlating them
      with the two pan-European clones.

PMID- 21722262
TI  - Evaluation of rK28 antigen for serodiagnosis of visceral Leishmaniasis in India.
AB  - Antibody detection is a safely applied method at the wide scale in diagnosis of
      visceral Leishmaniasis (VL). In order to further advance serodiagnosis, the rK28
      antigen has been recently introduced as a candidate for diagnosis of VL. We
      evaluated the sensitivity and specificity of the rK28 antigen in a micro-ELISA
      format in comparison to the rk39 antigen. The test was conducted on 252
      parasitologically confirmed VL cases, 103 endemic healthy controls, 95 non
      endemic healthy controls, 88 other infectious disease and 53 follow-up cases. Of
      252 parasitologically confirmed VL cases, 251 cases were reported positive by
      rK28 antigen, yielding 99.6% sensitivity (95% CI, 0.97-0.99), which was similar
      to the sensitivity of rK39 ELISA (99.6%) (95% CI, 0.97-0.99). Specificity of the
      rK28 antigen in non-endemic and endemic healthy controls was 100% (95% CI 0.96-1)
      and 94.17% (95% CI, 0.88-0.97), respectively. In 88 different diseases,
      specificity was 95.45% (95% CI, 0.84-0.96). With the rK39 antigen, specificity of
      non-endemic and endemic controls and different diseases was 100% (95% CI 0.96-1),
      92.23% (95% CI 0.85-0.96) and 96.59% (95% CI 0.90-0.98), respectively. Our
      results show that rK39 and rK28 antigens have similar sensitivity and specificity
      and rK28 can also be used as a serodiagnostic tool in the endemic population of
      Bihar.

PMID- 21722263
TI  - Colonization of paediatric lower respiratory tract with genital Mycoplasma
      species.
AB  - BACKGROUND AND OBJECTIVE: Recently, much attention has been given to the possible
      role played by pathogens that colonize neonatal or paediatric airway and their
      potential involvement in chronic respiratory disease. The goal of the current
      study was to evaluate the prevalence of Mycoplasma organisms in the BAL fluid of
      paediatric patients suffering from a variety of chronic respiratory diseases to
      determine if there was any clear disease association with bacterial presence.
      METHODS: We examined 319 paediatric BAL samples for the presence of M.genitalium,
      M.hominis, U.urealyticum, U.parvum and M.pneumoniae DNA with species-specific
      PCR. RESULTS: Mycoplasma DNA was found in 32.6% (104/319) of patient samples; 10%
      (32/319) for M.pneumoniae, 8.8% for U.parvum, 2.8% for U.urealyticum; 4.7% for
      M.hominis and 9.1% for M.genitalium. There were no significant clinical and
      laboratory differences except serum IgE in asthmatics according to Mycoplasma
      colonization or not. Elevated levels of IgE were found more often in Mycoplasma
      DNA-negative patients than patients with bacterial DNA, 85/109 versus 24/109
      respectively (P<0.0001). There was no difference in the frequency of Mycoplasmas
      between the asthmatics and the non-asthmatics; 30.6% (69/225) versus 37.2%
      (35/94) for Mycoplasma 16S DNA, and 8% versus 14.9% for M.pneumoniae,
      respectively. CONCLUSIONS: Our data indicate that in addition to M.pneumoniae,
      urogenital Mycoplasma species may colonize the airway of patients with chronic
      respiratory diseases. There was, however, no association between chronic asthma
      diagnosis and Mycoplasma colonization in this study.

PMID- 21722265
TI  - Invasion front-specific expression and prognostic  significance of microRNA in
      colorectal liver  metastases.
AB  - The tumor edge of colorectal cancer and its adjacent peritumoral tissue is
      characterized by an invasion front-specific expression of genes that contribute
      to angiogenesis or epithelial-to-mesenchymal transition. Dysregulation of these
      genes has a strong impact on the invasion behavior of tumor cells. However, the
      invasion front-specific expression of microRNA (miRNA) still remains unclear.
      Therefore, the aim of the present study was to investigate miRNA expression
      patterns at the invasion front of colorectal liver metastases. Laser
      microdissection of colorectal liver metastases was performed to obtain separate
      tissue compartments from the tumor center, tumor invasion front, liver invasion
      front and pure liver parenchyma. Microarray expression analysis revealed 23 miRNA
      downregulated in samples from the tumor invasion front with respect to the same
      miRNA in the liver, the liver invasion front or the tumor center. By comparing
      samples from the liver invasion front with samples from pure liver parenchyma,
      the tumor invasion front and the tumor center, 13 miRNA were downregulated. By
      quantitative RT-PCR, we validated the liver invasion front-specific
      downregulation of miR-19b, miR-194, let-7b and miR-1275 and the tumor invasion
      front-specific downregulation of miR-143, miR- 145, let-7b and miR-638.
      Univariate analysis demonstrated that enhanced expression of miR-19b and miR-194
      at the liver invasion front, and decreased expression of let-7 at the tumor
      invasion front, is an adverse prognostic marker of tumor recurrence and overall
      survival. In conclusion, the present study suggests that invasion front-specific
      downregulation of miRNA in colorectal liver metastases plays a pivotal role in
      tumor progression.

PMID- 21722266
TI  - HSulf-1 inhibits cell proliferation and invasion in  human gastric cancer.
AB  - The HSulf-1 gene encodes an extracellular 6-O-endosulfatase and regulates the
      sulfation status of heparan sulfate proteoglycans (HSPG). We have demonstrated
      that promoter hypermethylation is correlated with the HSulf-1 silencing in
      gastric cancer. To investigate the functional importance of HSulf-1 silencing in
      gastric cancer, we restored HSulf-1 expression in the gastric cancer cell line
      MKN28, which lacks endogenous HSulf-1. Following restoration of expression, HSulf
      1 inhibited cell proliferation, motility, and invasion in vitro, as well as
      significantly suppressing the MKN28 xenograft model (P < 0.05). No noticeable
      changes in proliferation and motility were observed following restoration of
      HSulf-1 in another gastric cancer cell line, namely AGS cells. Interestingly, in
      MKN28 cells, which have been reported to be dependent on extracellular Wnt
      signaling, we found that HSulf-1 inhibited the transcriptional activity of the
      Wnt / beta-catenin pathway and downregulated its targeted genes. Conversely, in
      AGS cells, in the constitutive Wnt / beta-catenin pathway is active, HSulf-1 had
      no effect on the activity of the Wnt / beta-catenin pathway. Furthermore,
      transfection of Wnt3a cDNA or beta-catenin shRNA resulted in rescue or
      enhancement, respectively, of the effects of HSulf-1 in MKN28 cells. Furthermore,
      HSPG epitope analysis confirmed that HSulf-1 affected the structure of heparan
      sulfate on the cell surface. Together, the results of the present study suggest
      that extracellular HSulf-1 may function as a negative regulator of proliferation
      and invasion in gastric cancer by suppressing Wnt / beta-catenin signaling at the
      cell surface.

PMID- 21722268
TI  - Vector volume manometry--methods and normal values.
AB  - BACKGROUND: Vector volume manometry (VVM) can be used to assess patients with
      fecal incontinence. The VVM may be performed using a station pull through, or an
      automated technique. Currently no standard technique or equipment exists to
      assess anal canal VVM. This study aimed to assess the different techniques to
      produce repeatable results, and generate normal values for the vector volume
      profile. METHODS: Anal canal VVM was performed using a water-perfused system on
      12 male and 12 nulliparous female volunteers. Manometry was performed with an
      automated puller withdrawn at 3 and 25mms(-1) using a station technique. The VVM
      profiles were calculated using 4, 8, and 16 channels. KEY RESULTS: The greatest
      repeatability of vector volume profile was seen with faster puller speed (25mms(
      1) ) and with an 8-channel catheter. Men had higher squeeze volumes, maximal
      squeeze pressure, average squeeze pressure, and squeeze high pressure zone
      length. Women had a significantly greater anal canal asymmetry on both station
      and automated pull through at rest and when squeezing. Squeeze vector volume of
      pressure, mean maximum squeeze pressure, and the average squeeze pressure were
      significantly higher when calculated using the station technique. CONCLUSIONS &
      INFERENCES: The faster puller speed has improved agreement between vector
      profiles, which is most marked during active contraction. The 8-channel catheters
      have the greatest agreement between profiles. There is variation in values
      between automated manometry and the stationary pull through technique. The
      improved repeatability in automated VVM for healthy controls should improve its
      diagnostic utility in patients with incontinence.

PMID- 21722267
TI  - Roles of AKT1 and AKT2 in non-small cell lung cancer  cell survival, growth, and
      migration.
AB  - Although AKT / protein kinase B is constitutively active in nonsmall cell lung
      cancer (NSCLC) cells and is an attractive target for enhancing the cytotoxicity
      of therapeutic agents, the distinct roles of the AKT isoforms in NSCLC are
      largely unknown. In the present study, we investigated the roles of AKT1 and AKT2
      in NSCLC cells using RNAi. The siRNA targeting of AKT1 or AKT2 effectively
      decreased protein levels of AKT1 and AKT2, respectively, in A549 and H460 cells.
      Cisplatin treatment of these cells increased apoptotic cell death compared with
      control. The siRNA-induced knockdown of AKT1 in H460 cells significantly
      decreased basal MEK/ ERK1 / 2 activity, resulting in nuclear factor-kappaB
      activation, whereas knockdown of AKT2 resulted in anti-apoptotic Bcl-2 family
      protein MCL-1 (MCL-1) cleavage, the collapse of mitochondrial membrane potential,
      cytochrome c release, and activation of the caspase cascade. Consequently, both
      siRNA treatments enhanced the chemosensitivity of H460 cells to cisplatin.
      However, neither AKT1 nor AKT2 siRNA treatment had any effect of p27 expression,
      and although both treatments tended to induced G2 /M phase arrest, the effect was
      not statistically significant. Treatment with AKT1 siRNA markedly decreased
      colony formation growth and migration, but AKT2 siRNA had no significant effects
      on these parameters. These data suggest that AKT1 and AKT2 both contribute to
      cell survival, albeit via different mechanisms, and that the effects on cell
      growth and migration are predominantly regulated by AKT1. These findings may aid
      in refining targeted strategies for the inhibition of AKT isoforms towards the
      sensitization of NSCLC cells to therapeutic agents.

PMID- 21722264
TI  - Interference of E2-2-mediated effect in endothelial  cells by FAM96B through its
      limited expression of  E2-2.
AB  - The basic helix-loop-helix protein E2-2 is known to play a role in quiescence of
      endothelial cells (ECs). However, it is unclear how the activity of E2-2 is
      controlled in the cells. In this study, we identified FAM96B as an interaction
      partner of E2-2. FAM96B interfered with E2-2-mediated effects on luciferase
      reporter activities. Furthermore, the suppression of vascular endothelial growth
      factor receptor 2 promoter activity by E2-2 was rescued by the expression of
      FAM96B in a dose-dependent manner. Interestingly, FAM96B decreased the expression
      of ectopic and endogenous E2-2 proteins. Mutational analysis revealed that the
      middle region of FAM96B is required for the limited expression of E2-2 protein.
      When FAM96B was expressed in ECs, the EC migration, proliferation, and tube
      formation were potentiated. Taken together, these findings suggest that FAM96B
      acts as a regulator of E2-2 through the control of its protein expression.

PMID- 21722269
TI  - The Trickster in the genome: contribution and control of transposable elements.
AB  - In mythology, the Trickster is an archetype who typically behaves selfishly and
      delights in playing tricks and breaking ordinary rules. In many myths and
      folktales, however, the Trickster also brings new knowledge and, ultimately, has
      positive effects on the community. Transposable elements (TEs) might have played
      such a role in the story of genome evolution. TEs can cause nonroutine genetic
      events like insertional mutations and ectopic recombination that provide a
      fundamental source of genetic variation, but they can also be a potential threat
      to genome integrity. Thus, the activity of TEs is usually controlled by an array
      of sophisticated mechanisms for genome defense. Recent findings indicate that TEs
      are important components of eukaryotic genomes, often to a much larger extent
      than ever anticipated. In this review, I focus on the contributions of TEs to
      various aspects of genome evolution. In addition, why TEs are specific targets
      for the genome defense mechanisms is discussed.

PMID- 21722270
TI  - Exploring the effectiveness of an integrated exercise/CBT intervention for young
      men's mental health.
AB  - OBJECTIVE: This pilot study investigated the effectiveness of a team-based
      sport/psychosocial intervention (Back of the Net, BTN) with an individual
      exercise (IE) and a control condition for the mental health of young men. DESIGN:
      Ten-week randomized control trial and eight-week post-intervention follow-up.
      Methods.  A total of 104 sedentary males aged between 18 and 40 years were
      recruited and randomly assigned to the BTN, IE, or a control condition. The BTN
      programme integrated team sport (i.e., football) and cognitive-behavioural
      techniques. IE sessions included aerobic and resistance training. The control
      group refrained from exercise. Participants completed the Beck Depression
      Inventory - 2nd Edition (BDI-II), the Social Provisions Scale (SPS) and a short
      qualitative questionnaire at pre-intervention, week 5, post-intervention and at 8
      week follow-up. RESULTS: Participants in both the BTN and the IE condition
      demonstrated a significant decrease in BDI-II scores compared to the control
      condition at post-intervention and at 8-week follow-up. The IE condition
      demonstrated significantly greater perceived social support than the BTN
      condition at week 5 and the control group at 8-week follow-up. Qualitative data
      support the main empirical findings. CONCLUSION: Exercise-based interventions
      were effective in reducing symptoms of depression in a non-clinical community
      sample of young men. The BTN programme demonstrated potential for improving the
      mental health of young men however larger scale community-based research is
      warranted to further examine the effectiveness of this type of intervention.

PMID- 21722271
TI  - Predictors of support provision: a study with couples adapting to incontinence
      following radical prostatectomy.
AB  - OBJECTIVES: Four domains of predictors of support provision were tested in
      couples facing an illness-related stress context. Predictor domains of partners'
      support provision to patients adapting to incontinence following prostatectomy
      included stress factors, recipient factors, provider factors, and relationship
      factors. METHODS: Data from 109 patients and their female partners were analysed.
      Couples provided data on five measurement occasions from 2 weeks to 1 year
      postsurgery. Predictors included patient's incontinence (stress factor),
      patient's support mobilization, affect and general self-efficacy (recipient
      factors), partner's affect and general self-efficacy (provider factors),
      partners' average waking time spent together, both partners' relationship
      satisfaction and partner's received support from patient (as an indicator of
      reciprocal support; relationship factors). RESULTS: Provider factors were not
      reliably associated with support provision, neither was patient negative affect.
      Stress and relationship factors accounted for outcome variance in the expected
      directions. Among recipient factors, mobilization of support and patient self
      efficacy were positively related with the outcome, whereas patient positive
      affect was negatively associated with support provision by partners. CONCLUSIONS:
      Findings on predictor domains are in line with other couple studies that used non
      illness-related stress contexts. Resemblance of findings points to
      generalizability of predictions across stress contexts varying in content,
      controllability, and duration.

PMID- 21722272
TI  - Effects of written emotional disclosure on implicit self-esteem and body image.
AB  - OBJECTIVES: Negative body image has a significant impact on self-esteem,
      disordered eating, and general health. Writing about distressing events and
      experiences has been found to have beneficial effects on psychological and
      physical health outcomes. This study investigated whether a written self
      disclosure intervention, compared to a writing about body image success stories
      (WSS) intervention, had beneficial effects on self-esteem and body image. DESIGN
      AND METHODS: One hundred and fifty-eight women (aged 18-22 years) were allocated
      to either: written emotional disclosure (WED); WSS; or a control, non-emotional
      writing condition. All measures were completed at baseline and at follow-up 4
      weeks later. RESULTS: A condition by time interaction was observed for implicit
      self-esteem, such that levels of self-esteem were improved 4 weeks later in the
      WED condition. Implicit self-esteem was also found to be greater following WED
      compared to the control condition, but not following WSS. CONCLUSIONS: This is
      the first study to demonstrate that WED has beneficial effects on implicit
      outcome measures such as self-esteem indicating that the positive effects of
      expressive writing may initially operate by influencing automatically activated
      attitudes towards the self. The impact of WED on implicit self-esteem may have
      implications for future health.

PMID- 21722273
TI  - The impact of biopsychosocial factors on quality of life: women with primary
      biliary cirrhosis on waiting list and post liver transplantation.
AB  - OBJECTIVES: Primary biliary cirrhosis (PBC) is the second most common reason for
      liver transplants among women in the USA. While survival rates are high, there is
      evidence of persistent problems post-transplant. This study aimed to identify
      significant contributors to quality of life (QOL) for women with PBC on waiting
      list (WL) and post-transplant (PT) and compare QOL in each group with US
      population norms. DESIGN: A cross-sectional, two-group study design was used.
      METHODS: WL and PT participants were recruited through medical centres and on
      line. QOL was measured by the Short Form-36 and an indicator of Social QOL
      created for this study. A biopsychosocial model incorporating demographic,
      biomedical, psychological, and sociological factors guided choice of variables
      affecting QOL. Analyses examined (1) all factors for differences between WL and
      PT groups, (2) association between factors and QOL outcomes within each group,
      (3) multivariate regression of QOL on factors in the model for the sample as a
      whole, and (4) comparison of QOL outcomes with national norms. RESULTS: One
      hundred women with PBC participated in the study, 25 on WL and 75 PT. Group
      comparisons showed improvement for PT participants in most biomedical and
      psychological variables and in QOL outcomes. QOL was related to many, but not
      all, of the variables in the model. In multivariate analysis, Fatigue,
      Depression, Coping, and Education - but not Transplant Status - were identified
      as indicators of QOL. Physical QOL improved significantly after 5 years PT, when
      it was no longer worse than national norms. Mental QOL remained worse than
      national norms despite distance in time from transplant. CONCLUSIONS: The model
      proved useful in identifying a range of factors that contributed to QOL for women
      with PBC before and after transplant. Recommendations were made for clinical
      practice to improve QOL through a combination of treatment and self-management.

PMID- 21722274
TI  - Women's experiences of pregnancy, childbirth, and the postnatal period in The
      Gambia: a qualitative study.
AB  - OBJECTIVE: In sub-Saharan African countries, there are unique cultural factors
      and adverse physical conditions that contribute to women's experiences of
      pregnancy and birth. The objective of this study was to qualitatively explore
      women's experiences of pregnancy, childbirth, the postnatal period, and maternal
      psychological distress in The Gambia. DESIGN AND METHODS: Semi-structured
      interviews were carried out with 55 women who had given birth within the previous
      year. RESULTS: Thematic analysis identified five themes: (1) transition to
      adulthood, (2) physical difficulties, (3) value of children in relation to
      others, (4) children as a strain, and (5) going through it alone. The results
      suggest that having a child is a defining point in women's lives associated with
      happiness and joy. However, women also described situations which could lead to
      unhappiness and distress in the perinatal period. A child conceived out of
      wedlock or a baby girl can be sources of distress because of negative cultural
      perceptions. The strain of having a child, particularly the additional financial
      burden, and minimal support from men were also a concern for women. Finally,
      women recognized the danger associated with delivery and expressed recurrent
      worries of complications during childbirth which could result in the death of
      them or the baby. CONCLUSIONS: Further research is needed to identify women
      vulnerable to psychological distress so that health services and target
      interventions can be developed accordingly.

PMID- 21722275
TI  - The lives of adults over 30 living with sickle cell disorder.
AB  - OBJECTIVES: The study investigated the lived experiences of adults over 30 years
      old living with sickle cell disorder (SCD) and sought to develop a model
      understanding participants' ability to function. DESIGN: Over a period of 10
      months, in-depth individual interviews were held with nine participants and three
      focus groups were held with six further participants. METHODS: Grounded theory, a
      qualitative methodology, was chosen to explore functioning across domains of
      experience in order to build an explanatory model. RESULTS: Physical,
      psychological, and social functioning were adversely effected by SCD. Access to
      and quality of resources including friends, family, and finances formed the
      context in which participants attempted to manage the disorder. Management of SCD
      improved over time as participants moved to acceptance of the condition. This
      allowed participants to strengthen their resilience by creating meaning,
      developing their identity, and actively coping with the effects of SCD, thus
      improving their ability to function and to appreciate life. CONCLUSIONS: The
      study demonstrates the considerable resilience of people over 30 with SCD,
      providing a positive and hopeful model which can be utilized clinically to
      support the functioning of people with SCD.

PMID- 21722276
TI  - The many faeces of colorectal cancer screening embarrassment: preliminary
      psychometric development and links to screening outcome.
AB  - OBJECTIVES: Although embarrassment may be among the most easily modified discrete
      emotional barriers to patients seeking health care or testing, work in the area
      of colorectal cancer (CRC) has been restricted by the absence of suitable
      instrumentation. The current report describes the development and validation of a
      self-report instrument assessing two specific aspects of CRC screening
      embarrassment and their links to screening outcomes. DESIGN: Convenience sampling
      was used to recruit 245 European American, African-American, and immigrant
      Caribbean community-dwelling men and women (aged 45-75 years) living in Brooklyn,
      New York. METHODS: Participants completed the measure of CRC screening
      embarrassment, an array of convergent and divergent validity measures including
      dispositional embarrassment, general medical embarrassment, neuroticism, trait
      emotion, social desirability, previous treatment avoidance because of
      embarrassment, relevant health characteristics, and a brief CRC screening
      history. RESULTS: As expected, CRC screening embarrassment was not unidimensional
      and had two reliable and distinct components, one concentrated on faecal/rectal
      embarrassment and the other on embarrassment arising from unwanted intimacy
      during examinations. In addition to demonstrating patterns of convergent and
      divergent validity consistent with their separation, multivariate analyses
      indicated that faecal/rectal embarrassment (but not intimacy concerns) predicted
      CRC screening frequency. CONCLUSIONS: The current report extends current
      understanding by identifying the specific sources of embarrassment that may
      contribute to patients' avoidance of CRC screening. Directions for future study
      and implications for clinical practice and interventions are discussed.

PMID- 21722277
TI  - Mixed feelings: ambivalence as a predictor of relapse in ex-smokers.
AB  - OBJECTIVES: Ambivalence can be viewed as a normal temporary psychological state
      in a decision process, for example, on quitting smoking. However, when
      ambivalence is still present after the decision has been made, it may undermine
      the motivation to stick to the decision. In smoking cessation, ambivalence can be
      expected to increase the risk for relapse. DESIGN: In a cohort of 352 ex-smokers,
      felt ambivalence measured at baseline was used to predict relapse after 1 month.
      RESULTS: Firstly, felt ambivalence was a predictor of relapse. Secondly, felt
      ambivalence moderated the strength of the relation between a psychological
      determinant of behaviour and actual behaviour: anticipated negative self
      evaluative emotions only predicted relapse when felt ambivalence was low.
      Thirdly, the relation of felt ambivalence with relapse was partly mediated by ex
      smokers' evaluations of risk situations (situations in which they used to smoke
      in the past). CONCLUSION: Ambivalence is related to relapse in different ways and
      in ex-smokers it may be conceptualized as a non-optimal decision process.
      Although the role of felt ambivalence needs further study, the data suggest that
      ambivalence must be taken into account in the practice of relapse prevention.

PMID- 21722278
TI  - Application of variable number of tandem repeat analysis to track Salmonella
      enterica ssp. enterica serovar Typhimurium infection of pigs reared on three
      British farms through the production cycle to the abattoir.
AB  - AIMS: This study investigated the diversity and persistence of Salmonella strains
      through the pork finishing cycle, from the farm into the abattoir. METHODS AND
      RESULTS: Isolates from four batches of finishers, from farm to abattoir, were
      used. Salmonella Typhimurium isolates were subjected to molecular typing using
      pulsed-field gel electrophoresis and variable number of tandem repeat analysis.
      The results demonstrated that infection was transferred from the farm to the
      abattoir. Within the abattoir, infection from individual pigs contaminated the
      exterior of the carcass and pigs exposed to Salmonella in the lairage were
      infected. CONCLUSIONS: Salmonella can be introduced at various points in the pig
      production and slaughter process. Carcass contamination may arise from infection
      on farm and exposure in the lairage and abattoir environment. Pigs could be
      contaminated by previous batches of pigs while in lairage or during the dressing
      process. Salmonella infection on farms is dynamic with multiple serovars present
      from different sources. SIGNIFICANCE AND IMPACT OF THE STUDY: Molecular typing
      methods facilitated the tracing of Salm. Typhimurium through the production cycle
      and differentiated some farm-acquired from abattoir-acquired strains. The
      findings emphasize the importance of integrated control strategies along the pork
      food chain.

PMID- 21722279
TI  - Susceptibility of the cactus weevil Metamasius spinolae to Beauveria bassiana and
      Metarhizium anisopliae under laboratory and field conditions.
AB  - AIMS: To evaluate different entomopathogenic fungal isolates against the cactus
      weevil Metamasius spinolae under laboratory and field conditions, and select an
      isolate to be used as a tool in the management of this insect pest. METHODS AND
      RESULTS: Four experiments were carried out. The effect of temperature on the in
      vitro growth of eight isolates of entomopathogenic fungi (two Metarhizium
      anisopliae and six Beauveria bassiana) was assessed. The susceptibility of adult
      M. spinolae to the same isolates was evaluated. Using three selected isolates,
      the interaction between susceptibility and sex of the insect was studied.
      Finally, a field experiment was carried out to evaluate infection of adult M.
      spinolae by the same three isolates under natural abiotic conditions. Overall,
      growth rate was greatest at 25 degrees C for all the isolates. In vitro growth of
      M. anisopliae was greater than B. bassiana. Mortality of adult M. spinolae was
      greater when inoculated with B. bassiana compared with isolates of M. anisopliae.
      Susceptibility had no interaction with the sex of the insect. The proportion of
      insects succumbing to infection was smaller when incubated under field conditions
      than when incubated under laboratory conditions. CONCLUSIONS: The experiments
      described here showed a complex interaction between entomopathogenic fungi and M.
      spinolae, and these data allows us to select isolate Bb107 as a first step
      towards its use in the management of this pest insect. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Our results showed that entomopathogenic fungi can be used for the
      control of M. spinolae, which may help reduce the use of chemical insecticides
      and, therefore, the exposure of Opuntia ficus-indica producers to pesticides.

PMID- 21722281
TI  - Derlin-dependent retrograde transport from endosomes to the Golgi apparatus.
AB  - Cells have to maintain stable plasma membrane protein and lipid compositions
      under normal conditions and to remodel their plasma membranes in response to
      stimuli. This maintenance and remodeling require that integral membrane proteins
      at the plasma membrane that become misfolded, because of the relatively harsher
      extracellular milieu or carbohydrate and amino acid sequence changes, are
      degraded. We had previously shown that Derlin proteins, required for quality
      control mechanisms in the endoplasmic reticulum, also localize to endosomes and
      function in the degradation of misfolded integral membrane proteins at the plasma
      membrane. In this study, we show that Derlin proteins physically associate with
      sorting nexins that function in retrograde membrane transport from endosomes to
      the Golgi apparatus. Using genetic studies in Caenorhabditis elegans and ricin
      pulse-chase analyses in murine RAW264.7 macrophages, we show that the Derlin
      sorting nexin interaction is physiologically relevant. Our studies suggest that
      at least some integral membrane proteins that are misfolded at the plasma
      membrane are retrogradely transported to the Golgi apparatus and ultimately to
      the endoplasmic reticulum for degradation via resident quality control
      mechanisms.

PMID- 21722280
TI  - How ubiquitin functions with ESCRTs.
AB  - The endosomal-sorting complex required for transport (ESCRT) apparatus has
      multiple ubiquitin (Ub)-binding domains and participates in a wide variety of
      cellular processes. Many of these ESCRT-dependent processes are keenly regulated
      by Ub, which serves as a lysosomal-sorting signal for membrane proteins targeted
      into multivesicular bodies (MVBs) and which may serve as a mediator of viral
      budding from the cell surface. Hints that both ESCRTs and Ub work together in the
      processes such as cytokinesis, transcription and autophagy are beginning to
      emerge. Here, we explore the relationship between ESCRTs and Ub in MVB sorting
      and viral budding.

PMID- 21722282
TI  - ESCRT machinery and cytokinesis: the road to daughter cell separation.
AB  - The endosomal sorting complex required for transport (ESCRT) machinery is a set
      of cellular protein complexes required for at least three topologically
      equivalent membrane scission events, namely multivesicular body (MVB) formation,
      retroviral particle release and midbody abscission during cytokinesis. Recently,
      several studies have explored the mechanism by which the core ESCRT-III subunits
      mediate membrane scission and might be differentially required according to the
      functions of the pathway. In this review, we discuss the links between the ESCRT
      machinery and cytokinesis, with special focus on abscission initiation and
      regulation.

PMID- 21722283
TI  - The progression from obesity to type 2 diabetes in Alstrom syndrome.
AB  - BACKGROUND: Alstrom syndrome (ALMS) is a rare autosomal recessive monogenic
      disease associated with obesity, hyperinsulinemia, and alterations of glucose
      metabolism that often lead to the development of type 2 diabetes at a young age.
      OBJECTIVE: To study the relationship between weight and metabolism in a group of
      ALMS patients and matched controls. RESEARCH DESIGN AND METHODS: Fifteen ALMS
      patients (eight males, seven females; aged 3-51) were compared in a cross
      sectional study with an age- and weight-matched control population.
      Anthropometric parameters, fat mass, glucose and insulin secretion in basal and
      dynamic oral glucose tolerance test (OGTT) conditions were measured. Furthermore,
      anthropometric and body composition data were obtained from an international
      group of 27 ALMS patients (13 males, 14 females, age range: 4-29 yr). RESULTS: In
      ALMS we observed an inverse correlation between age and standard deviation scores
      for height, weight, and body mass index. The OGTT glycemic curves of ALMS
      subjects were similar to those of age-matched controls, whereas insulin response
      was clearly greater. In ALMS individuals the insulin response showed a reduction
      with age. We documented pathologic values of the derived indices homeostasis
      model assessment of insulin resistance (HOMA-IR), insulin sensitivity index,
      HOMA%beta-cell and insulinogenic index in ALMS, but unlike the insulin-resistance
      indices, the beta-cell function indices showed a significant reduction with age.
      CONCLUSIONS: In ALMS the progression from the early onset obesity toward the
      impaired fasting glucose or impaired glucose tolerance and overt diabetes is
      mostly because of a progressive failure of beta-cell insulin secretion without
      any further worsening of insulin resistance with age, even in the presence of
      weight reduction.

PMID- 21722284
TI  - Effectiveness of sensor-augmented pump therapy in children and adolescents with
      type 1 diabetes in the STAR 3 study.
AB  - OBJECTIVE: Maintenance of appropriate A1C values and minimization of
      hyperglycemic excursions are difficult for many pediatric patients with type 1
      diabetes. Continuous glucose monitoring (CGM) sensor-augmented pump (SAP) therapy
      is an alternative to multiple daily injection (MDI) therapy in this population.
      RESEARCH DESIGN AND METHODS: Sensor-augmented pump therapy for A1C reduction
      (STAR 3) was a 1-yr trial that included 82 children (aged 7-12) and 74
      adolescents (aged 13-18) with A1C values ranging from 7.4 to 9.5% who were
      randomized to either SAP or MDI therapy. Quarterly A1C values were obtained from
      all subjects. CGM studies were carried out at baseline, 6 months, and 12 months
      to quantify glycemic excursions [calculated as area under the glucose
      concentration-time curve (AUC)] and variability. In the SAP group, sensor
      compliance was recorded. RESULTS: Baseline A1C values were similar in subjects
      randomized to the SAP (8.26 +/- 0.55%) and MDI groups (8.30 +/- 0.53%). All
      subsequent A1C values showed significant (p < 0.05) treatment group differences
      favoring SAP therapy. Compared with the MDI group, subjects in the SAP group were
      more likely to meet age-specific A1C targets and had lower AUC values for
      hyperglycemia with no increased risk of hypoglycemia. Glucose variability
      improved in the SAP group compared to the MDI group. Children wore CGM sensors
      more often and were more likely to reach age-specific A1C targets than
      adolescents. CONCLUSIONS: SAP therapy allows both children and adolescents with
      marginally or inadequately controlled type 1 diabetes to reduce A1C values,
      hyperglycemic excursions, and glycemic variability in a rapid, sustainable, and
      safe manner.

PMID- 21722286
TI  - Shiga toxins induce autophagy leading to differential signalling pathways in
      toxin-sensitive and toxin-resistant human cells.
AB  - The bacterial virulence factors Shiga toxins (Stxs) are expressed by Shigella
      dysenteriae serotype 1 and certain Escherichia coli strains. Stxs are protein
      synthesis inhibitors and induce apoptosis in many cell types. Stxs induce
      apoptosis via prolonged endoplasmic reticulum stress signalling to activate both
      extrinsic and intrinsic pathways in human myeloid cells. Studies have shown that
      autophagy, a lysosome-dependent catabolic process, may be associated with
      activation of pro-survival or death processes. It is currently unknown if
      autophagy contributes to apoptosis or protects cells from Stxs. To study cellular
      responses to Stxs, we intoxicated toxin-sensitive cells (THP-1 and HK-2 cells),
      and toxin-resistant cells (primary human monocyte-derived macrophages) and
      examined toxin intracellular trafficking and autophagosome formation. Stxs
      translocated to different cell compartments in toxin-resistant versus toxin
      sensitive cells. Confocal microscopy revealed autophagosome formation in both
      toxin-resistant and toxin-sensitive cells. Proteolytic cleavage of Atg5 and
      Beclin-1 plays pivotal roles in switching non-cytotoxic autophagy to cell death
      signalling. We detected cleaved forms of Atg5 and Beclin-1 in Stx-treated toxin
      sensitive cells, while cleaved caspases, calpains, Atg5 and Beclin-1 were not
      detected in toxin-resistant primary human monocytes and macrophages. These
      findings suggest that toxin sensitivity correlates with caspase and calpain
      activation, leading to Atg5 and Beclin-1 cleavage.

PMID- 21722287
TI  - Impaired antibody memory to varicella zoster virus in HIV-infected children: low
      antibody levels and avidity*.
AB  - OBJECTIVE: HIV-infected children have impaired antibody responses after exposure
      to certain antigens. Our aim was to determine whether HIV-infected children had
      lower varicella zoster virus (VZV) antibody levels compared with HIV-infected
      adults or healthy children and, if so, whether this was attributable to an
      impaired primary response, accelerated antibody loss, or failure to reactivate
      the memory VZV response. METHODS: In a prospective, cross-sectional and
      retrospective longitudinal study, we compared antibody responses, measured by
      enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV
      infected children and 78 HIV-infected adults treated with antiretroviral therapy,
      followed over 10 years, and 97 age-matched healthy children. We also tested
      antibody avidity in HIV-infected and healthy children. RESULTS: Median anti-VZV
      immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults
      (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over
      time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36
      72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV
      infected children. Anti-VZV antibodies did not decline more rapidly in HIV
      infected children than in adults. Antibody levels increased with age in healthy
      (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in
      HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody
      avidity was lower in HIV-infected than healthy children (P<0.001). A direct
      correlation between anti-VZV IgG level and avidity was present in HIV-infected
      children (P=0.001), but not in healthy children. CONCLUSION: Failure to maintain
      anti-VZV IgG levels in HIV-infected children results from failure to reactivate
      memory responses. Further studies are required to investigate long-term
      protection and the potential benefits of immunization.

PMID- 21722290
TI  - Editorial comment: Primary full-gland prostate cryoablation in older men (> age
      of 75 years): results from 860 patients tracked with the COLD registry.

PMID- 21722288
TI  - Primary full-gland prostate cryoablation in older men (> age of 75 years):
      results from 860 patients tracked with the COLD Registry.
AB  - Study Type - Therapy (outcomes research). LEVEL OF EVIDENCE: 2c. What's known on
      the subject? and What does the study add? Most elderly patient with prostate
      cancer undergo radiation therapy, but cryoablation has gained popularity. This
      study demonstrates the safety and efficiency of this new approach. OBJECTIVE: *
      To report on the largest data set regarding outcomes for whole gland prostate
      cryoablation as a primary treatment of prostate cancer in older men, which we
      empirically defined as age >75 years. MATERIALS AND METHODS: * The COLD (Cryo On
      Line Data) Registry consists of case report forms with pre- and post-treatment
      information obtained from patients undergoing prostate cryoablation. * A total of
      860 patients were stratified into low-, intermediate- and high-risk groups
      (D'Amico 2003 risk definitions). * Biochemical disease-free survival (bDFS) was
      defined according to the traditional American Society for Therapeutic Radiology
      and Oncology definition (3 increases) and the newer (Phoenix) definition (nadir
      +2). * Biopsy was performed at physician discretion but most commonly for cause
      if a patient had an increasing or suspicious prostate-specific antigen level
      (PSA). RESULTS: * The median age was 79 years (76-91) and the median follow-up
      was 16 months (4-60). * The 5-year [95% confidence interval (CI)] bDFS for the
      entire population using ASTRO and Phoenix definitions was 79% (4%) and 62.6%
      (8.3%), respectively. * Stratified by risk group, 5-year bDFS (ASTRO) was 82.4%
      (7.9%), 78.3% (5.8%) and 77.6% (7.7%) for low, moderate and high risk,
      respectively. * Using the Phoenix definition, 5-year bDFS was 74.9%+/- 15.3%,
      61.4%+/- 13.2% and 58.0%+/- 11.9% for low-, moderate- and high-risk groups,
      respectively. * Incontinence was reported in eight patients (0.9%). CONCLUSION: *
      Whole gland cryoablation in older men maintains oncological efficacy similar to
      that of younger men without increased morbidity.

PMID- 21722289
TI  - Multilocular cystic renal cell carcinoma: clinicopathological features and
      preoperative prediction using multiphase computed tomography.
AB  - OBJECTIVE: * To analyse the clinicopathological and radiological features of
      multilocular cystic renal cell carcinoma (MCRCC) and to determine the
      preoperative factors differentiating MCRCC from other cystic RCC (CRCC). PATIENTS
      AND METHODS: * The medical records of 53 patients with complex cystic renal
      masses evaluated by multiphase computed tomography (CT), surgically removed and
      confirmed as sporadic RCC were reviewed. * Of these 53 patients, 23 were
      classified as having MCRCC and 30 as other CRCCs, defined as RCCs with extensive
      cystic change or cystic necrosis. * Another 22 patients were treated for complex
      cystic renal masses presumed to be RCC and diagnosed as having benign cyst.
      RESULTS: * Benign cysts and MCRCCs were significantly more likely to be of
      Bosniak classification III than other CRCCs (77% vs 61% vs 27%, P= 0.001). * The
      mean Hounsfield unit (HU) during the corticomedullary phase (CMP) was
      significantly higher in other CRCCs, with HU >=38 having 83% sensitivity and 80%
      specificity for predicting other CRCCs. * In a multiple regression model, Bosniak
      classification and mean HU during CMP were independent factors predictive of
      other CRCCs. * In the 41 patients with masses >4 cm in diameter, the combination
      of Bosniak classification IV and HU >=38 during CMP showed 63% sensitivity, 96%
      specificity, 91% positive predictive value and 80% negative predictive value,
      yielding 2% false-positive and 15% false-negative rates. CONCLUSIONS: * The mean
      HU during CMP and Bosniak classification can differentiate MCRCC from other
      CRCCs. * This could help in selecting an appropriate surgical method, such as
      nephron-sparing surgery, for complex cystic renal masses >4 cm.

PMID- 21722292
TI  - Secrets of the subterranean pathosystem of Armillaria.
AB  - Armillaria root disease affects fruit and nut crops, timber trees and ornamentals
      in boreal, temperate and tropical regions of the world. The causal pathogens are
      members of the genus Armillaria (Basidiomycota, Physalacriaceae). This review
      summarizes the state of knowledge and highlights recent advances in Armillaria
      research. TAXONOMY: Armillaria includes more than 40 morphological species.
      However, the identification and delineation of species on the basis of
      morphological characters are problematic, resulting in many species being
      undetected. Implementation of the biological species' concept and DNA sequence
      comparisons in the contemporary taxonomy of Armillaria have led to the discovery
      of a number of new species that are not linked to described morphological
      species. HOST RANGE: Armillaria exhibits a range of symbioses with both plants
      and fungi. As plant pathogens, Armillaria species have broad host ranges,
      infecting mostly woody species. Armillaria can also colonize orchids Galeola and
      Gastrodia but, in this case, the fungus is the host and the plant is the
      parasite. Similar to its contrasting relationships with plants, Armillaria acts
      as either host or parasite in its interactions with other fungi. Disease control:
      Recent research on post-infection controls has revealed promising alternatives to
      the former pre-plant eradication attempts with soil fumigants, which are now
      being regulated more heavily or banned outright because of their negative effects
      on the environment. New study tools for genetic manipulation of the pathogen and
      characterization of the molecular basis of the host response will greatly advance
      the development of resistant rootstocks in a new stage of research. The depth of
      the research, regardless of whether traditional or genomic approaches are used,
      will depend on a clear understanding of where the different propagules of
      Armillaria attack a root system, which of the pathogen's diverse biolymer
      degrading enzymes and secondary metabolites facilitate infection, and how the
      course of infection differs between resistant and susceptible hosts.

PMID- 21722293
TI  - Narrowing down the apricot Plum pox virus resistance locus and comparative
      analysis with the peach genome syntenic region.
AB  - Sharka disease, caused by the Plum pox virus (PPV), is one of the main limiting
      factors for stone fruit crops worldwide. Only a few resistance sources have been
      found in apricot (Prunus armeniaca L.), and most studies have located a major PPV
      resistance locus (PPVres) on linkage group 1 (LG1). However, the mapping accuracy
      was not sufficiently reliable and PPVres was predicted within a low confidence
      interval. In this study, we have constructed two high-density simple sequence
      repeat (SSR) improved maps with 0.70 and 0.68 markers/cm, corresponding to LG1 of
      'Lito' and 'Goldrich' PPV-resistant cultivars, respectively. Using these maps,
      and excluding genotype-phenotype incongruent individuals, a new binary trait
      locus (BTL) analysis for PPV resistance was performed, narrowing down the PPVres
      support intervals to 7.3 and 5.9 cm in 'Lito' and 'Goldrich', respectively.
      Subsequently, 71 overlapping oligonucleotides (overgo) probes were hybridized
      against an apricot bacterial artificial chromosome (BAC) library, identifying 870
      single BACs from which 340 were anchored onto a map region of approximately 30-40
      cm encompassing PPVres. Partial BAC contigs assigned to the two allelic
      haplotypes (resistant/susceptible) of the PPVres locus were built by high
      information content fingerprinting (HICF). In addition, a total of 300 BAC
      derived sequences were obtained, and 257 showed significant homology with the
      peach genome scaffold_1 corresponding to LG1. According to the peach syntenic
      genome sequence, PPVres was predicted within a region of 2.16 Mb in which a few
      candidate resistance genes were identified.

PMID- 21722291
TI  - Evaluating the utility of a preoperative nomogram for predicting 90-day mortality
      following radical cystectomy for bladder cancer.
AB  - OBJECTIVE: To evaluate the performance of the Isbarn nomogram for predicting 90
      day mortality following radical cystectomy in a contemporary series. PATIENTS AND
      METHODS: We identified 1141 consecutive radical cystectomy patients treated at
      our institution between 1995 and 2005 with at least 90 days of follow-up. We
      applied the published nomogram to our cohort, determining its discrimination,
      with the area under the receiver operating characteristic curve (AUC), and
      calibration. We further compared it with a simple model using age and the
      Charlson comorbidity score. RESULTS: Our cohort was similar to that used to
      develop the Isbarn nomogram in terms of age, gender, grade and histology;
      however, we observed a higher organ-confined (<=pT2, N0) rate (52% vs 24%) and a
      lower overall 90-day mortality rate [2.8% (95% confidence interval 1.9%, 3.9%) vs
      3.9%]. The Isbarn nomogram predicted individual 90-day mortality in our cohort
      with moderate discrimination [AUC 73.8% (95% confidence interval 64.4%, 83.2%)].
      In comparison, a model using age and Charlson score alone had a bootstrap
      corrected AUC of 70.2% (95% confidence interval 67.2%, 75.4%). CONCLUSIONS: The
      Isbarn nomogram showed moderate discrimination in our cohort; however, the
      exclusion of important preoperative comorbidity variables and the use of
      postoperative pathological stage limit its utility in the preoperative setting.
      The use of a simple model combining age and Charlson score yielded similar
      discriminatory ability and underscores the significance of individual patient
      variables in predicting outcomes. An accurate tool for predicting postoperative
      morbidity/mortality following radical cystectomy would be valuable for treatment
      planning and counselling. Future nomogram design should be based on preoperative
      variables including individual risk factors, such as comorbidities.

PMID- 21722294
TI  - The FRP1 F-box gene has different functions in sexuality, pathogenicity and
      metabolism in three fungal pathogens.
AB  - Plant-pathogenic fungi employ a variety of infection strategies; as a result,
      fungi probably rely on different sets of proteins for successful infection. The F
      box protein Frp1, only present in filamentous fungi belonging to the
      Sordariomycetes, Leotiomycetes and Dothideomycetes, is required for nonsugar
      carbon catabolism and pathogenicity in the root-infecting fungus Fusarium
      oxysporum. To assess the role of Frp1 in other plant-pathogenic fungi, FRP1
      deletion mutants were generated in Fusarium graminearum and Botrytis cinerea, and
      their phenotypes were analysed. Deletion of FgFRP1 in F. graminearum led to
      impaired infection of barley roots, but not of aerial plant parts. Deletion of
      BcFRP1 in B. cinerea did not show any effect on pathogenicity. Sexual
      reproduction, however, was impaired in both F. graminearum and B. cinerea FRP1
      deletion mutants. The mutants of all three fungi displayed different phenotypes
      when grown on an array of carbon sources. The F. oxysporum and B. cinerea
      deletion mutants showed opposite growth phenotypes on sugar and nonsugar carbon
      sources. Replacement of FoFRP1 in F. oxysporum with the B. cinerea BcFRP1
      resulted in the restoration of pathogenicity, but also in a switch from impaired
      growth on nonsugar carbon sources to impaired growth on sugar carbon sources.
      This effect could be ascribed in part to the B. cinerea BcFRP1 promoter sequence.
      In conclusion, the function of the F-box protein Frp1, despite its high sequence
      conservation, is not conserved between different fungi, leading to differential
      requirements for pathogenicity and carbon source utilization.

PMID- 21722295
TI  - The Botrytis cinerea phytotoxin botcinic acid requires two polyketide synthases
      for production and has a redundant role in virulence with botrydial.
AB  - The grey mould fungus Botrytis cinerea produces two major phytotoxins, the
      sesquiterpene botrydial, for which the biosynthesis gene cluster has been
      characterized previously, and the polyketide botcinic acid. We have identified
      two polyketide synthase (PKS) encoding genes, BcPKS6 and BcPKS9, that are up
      regulated during tomato leaf infection. Gene inactivation and analysis of the
      secondary metabolite spectra of several independent mutants demonstrated that
      both BcPKS6 and BcPKS9 are key enzymes for botcinic acid biosynthesis. We showed
      that BcPKS6 and BcPKS9 genes, renamed BcBOA6 and BcBO9 (for B. cinerea botcinic
      acid biosynthesis), are located at different genomic loci, each being adjacent to
      other putative botcinic acid biosynthetic genes, named BcBOA1 to BcBOA17.
      Putative orthologues of BcBOA genes are present in the closely related fungus
      Sclerotinia sclerotiorum, but the cluster organization is not conserved between
      the two species. As for the botrydial biosynthesis genes, the expression of BcBOA
      genes is co-regulated by the Galpha subunit BCG1 during both in vitro and in
      planta growth. The loss of botcinic acid production does not affect virulence on
      bean and tomato leaves. However, double mutants that do not produce botcinic acid
      or botrydial (bcpks6Deltabcbot2Delta) exhibit markedly reduced virulence. Hence,
      a redundant role of botrydial and botcinic acid in the virulence of B. cinerea
      has been demonstrated.

PMID- 21722296
TI  - Genome sequencing and comparative analysis of the carrot bacterial blight
      pathogen, Xanthomonas hortorum pv. carotae M081, for insights into pathogenicity
      and applications in molecular diagnostics.
AB  - Xanthomonas hortorum pv. carotae (Xhc) is an economically important pathogen of
      carrots. Its ability to epiphytically colonize foliar surfaces and infect seeds
      can result in bacterial blight of carrots when grown in warm and humid regions.
      We used high-throughput sequencing to determine the genome sequence of isolate
      M081 of Xhc. The short reads were de novo assembled and the resulting contigs
      were ordered using a syntenic reference genome sequence from X. campestris pv.
      campestris ATCC 33913. The improved, high-quality draft genome sequence of Xhc
      M081 is the first for its species. Despite its distance from other sequenced
      xanthomonads, Xhc M081 still shared a large inventory of orthologous genes,
      including many clusters of virulence genes common to other foliar pathogenic
      species of Xanthomonas. We also mined the genome sequence and identified at least
      21 candidate type III effector genes. Two were members of the avrBs2 and xopQ
      families that demonstrably elicit effector-triggered immunity. We showed that
      expression in planta of these two type III effectors from Xhc M081 was sufficient
      to elicit resistance gene-mediated hypersensitive responses in heterologous
      plants, indicating a possibility for resistance gene-mediated control of Xhc.
      Finally, we identified regions unique to the Xhc M081 genome sequence, and
      demonstrated their potential in the design of molecular diagnostics for this
      pathogen.

PMID- 21722298
TI  - Flux of nitric oxide between the necrotrophic pathogen Botrytis cinerea and the
      host plant.
AB  - Nitric oxide (NO) production by Botrytis cinerea and the effect of externally
      supplied NO were studied during saprophytic growth and plant infection.
      Fluorescence analysis with 4,5-diaminofluorescein diacetate and electrochemical
      studies were conducted in vitro between 4 and 20 h of incubation and in planta
      between 15 and 75 h post-inoculation. The production of NO by B. cinerea in vitro
      was detected inside the germinating spores and mycelium and in the surrounding
      medium. In planta production of NO showed a large variation that was dependent on
      the host plant and developmental stage of the infection. The induced production
      of NO was detected from 16 h of in vitro incubation in response to externally
      added NO. The production of NO by B. cinerea is probably modulated to promote
      fungal colonization of the plant tissue. The production of NO which diffuses
      outside the fungal cells and the induction of NO production by exogenous NO open
      up the possibility of NO cross-talk between the fungus and the plant. Finally,
      the existence of an NO concentration threshold is proposed, which may increase or
      reduce the plant defence against necrotrophic fungal pathogens.

PMID- 21722297
TI  - Satellite RNA reduces expression of the 2b suppressor protein resulting in the
      attenuation of symptoms caused by Cucumber mosaic virus infection.
AB  - Satellite RNAs (satRNAs) depend on cognate helper viruses for replication,
      encapsidation, movement and transmission. Many satRNAs with different symptom
      modulation effects have been reported. The pathogenicity of satRNAs is thought to
      be the result of a direct interaction among the satRNA, helper viruses and host
      factors by unknown mechanisms. To understand the effect of satRNA of Cucumber
      mosaic virus (a severe field ShanDong strain, SD-CMV) on pathogenicity, and the
      possible involvement of host RNA silencing pathways in pathogenicity, we
      constructed biologically active CMV cDNA clones and a CMV-Delta2b mutant lacking
      the open reading frame of 2b, a silencing suppressor protein, in order to infect
      Nicotiana benthamiana and Arabidopsis with or without SD-satRNA. We found that SD
      satRNA reduced the accumulation of the 2b protein and its coding RNA4A and
      attenuated the yellowing caused by SD-CMV infection. Small RNA analysis indicated
      that the 2b protein interfered with RNA silencing, specifically in the synthesis
      of CMV RNA3-derived small interfering RNAs (R3-siRNAs). The accumulation of R3
      siRNAs in CMV-Delta2b infection was reduced in the presence of satRNA, for which
      greater accumulation of satRNA-derived siRNAs (satsiRNAs) was detected. Our
      results suggest that abundant SD-satRNA serving as target for RNA silencing may
      play a role in protecting helper CMV RNA, especially, subgenomic RNA4, from being
      targeted by RNA silencing. This compensates for the increase in RNA silencing
      resulting from the reduction in expression of the 2b suppressor in the presence
      of satRNA. Our data provide evidence that a plant silencing mechanism is involved
      in the pathogenicity of satRNA.

PMID- 21722300
TI  - Chronic kidney disease is a growing worldwide public health problem. Preface.

PMID- 21722299
TI  - The prevalence of increased central adiposity in Australian school children 1985
      to 2007.
AB  - The epidemic of obesity as measured by body mass index (BMI) maybe plateauing.
      However, studies using skin-fold and waist circumference measurements suggest
      that BMI may underestimate changes in fatness in children. In this study we
      examine changes in waist circumference and waist-to-height ratio (WHtR) in
      Australian children between 1985 and 2007, by undertaking secondary data analysis
      of three national data sets. The mean waist circumference z-score for boys
      increased from -0.02 (95% CI -0.05 to 0.01) in 1985, to 0.33 (0.26 to 0.40) in
      1995 and 0.41 (0.35 to 0.47) in 2007 and was greater (P<0.001) than the increase
      in BMI z-score. The increase in mean waist circumference z-score for girls was
      greater (P<0.001) than boys and increased from -0.02 (0.05 to 0.01) in 1985, to
      0.33 (0.26 to 0.41) in 1995 and to 0.57 (0.51 to 0.63) in 2007. The number of
      children with a WHtR >= 0.5 increased from 8.6% in 1985, to 13.6% in 1995 and
      18.3% in 2007. Between 1985 and 2007 central adiposity increased at a faster rate
      than total adiposity, particularly in girls. The secular increase in waist
      circumference and WHtR is concerning as measures of central adiposity are
      associated with metabolic and cardiovascular risk.

PMID- 21722301
TI  - Clinical experience with nadroparin in patients undergoing dialysis for renal
      impairment.
AB  - Dialysis procedures are life-sustaining renal replacement therapies indicated for
      patients with limited or no kidney function. The formation of clots in the
      extracorporeal circuit during dialysis is an undesirable event. Anticoagulation
      is therefore routinely practiced in this context. Unfractionated heparin (UFH) is
      largely used in dialysis patients. However, except in patients with an elevated
      risk of bleeding, the 2002 European Best Practice Guidelines Expert Group on
      Hemodialysis recommended the use of low-molecular-weight heparins over UFH, in
      view of their equal efficacy, improved safety, and easy handling. Low-molecular
      weight heparins comprise several drugs, differing in a number of pharmacological
      and clinical properties. This manuscript reviews the data obtained with
      nadroparin, a low-molecular-weight heparin studied extensively in dialysis
      patients. Thus, several studies investigated the benefit of nadroparin vs. UFH,
      other low-molecular-weight heparins, or citrate in patients undergoing
      intermittent hemodialysis. Overall, they showed that a single intravenous bolus
      dose of nadroparin, adjusted according to body weight, was effective and safe for
      maintaining the patency of the extracorporeal circuit during intermittent
      hemodialysis sessions lasting up to 6 hours, in both adults and children with end
      stage renal failure. In contrast to UFH, nadroparin required no laboratory
      monitoring of anticoagulant activity owing to the reliable anticoagulant response
      following its administration. Compared with UFH, nadroparin was beneficial in
      terms of lipid and possibly bone parameters. Nadroparin administered by a bolus
      dose, followed by a continuous infusion was also shown to be effective and safe
      in patients undergoing continuous renal replacement therapy for acute renal
      failure.

PMID- 21722302
TI  - Unfolded proteins and endoplasmic reticulum stress in neurodegenerative
      disorders.
AB  - The stimuli for neuronal cell death in neurodegenerative disorders are multi
      factorial and may include genetic predisposition, environmental factors, cellular
      stressors such as oxidative stress and free radical production, bioenergy
      failure, glutamate-induced excitotoxicity, neuroinflammation, disruption of
      Ca(2+) -regulating systems, mitochondrial dysfunction and misfolded protein
      accumulation. Cellular stress disrupts functioning of the endoplasmic reticulum
      (ER), a critical organelle for protein quality control, leading to induction of
      the unfolded protein response (UPR). ER stress may contribute to
      neurodegeneration in a range of neurodegenerative disorders. This review
      summarizes the molecular events occurring during ER stress and the unfolded
      protein response and it specifically evaluates the evidence suggesting the ER
      stress response plays a role in neurodegenerative disorders.

PMID- 21722303
TI  - Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted
      tumour growth.
AB  - Accumulating evidence suggests that chronic stress can be a cofactor for the
      initiation and progression of cancer. Here we evaluated the role of endothelial
      nitric oxide synthase (eNOS) in stress-promoted tumour growth of murine B16F10
      melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed
      increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced
      thymus weight and a 3.61-fold increase in tumour growth in respect to no-stressed
      animals. Tumour growth was significantly reduced in mice treated with the beta
      antagonist propranolol. Tumour samples obtained from stressed mice displayed high
      levels of vascular endothelial growth factor (VEGF) protein in
      immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide is
      a relevant factor in angiogenesis, we assessed the levels of eNOS protein by
      Western blot analysis. We found a significant increase in eNOS levels in tumour
      samples from stressed mice, indicating an involvement of this enzyme in stress
      induced tumour growth. Accordingly, chronic stress did not promote tumour growth
      in eNOS(-/-)  mice. These results disclose for the first time a pivotal role for
      eNOS in chronic stress-induced initiation and promotion of tumour growth.

PMID- 21722304
TI  - Type 2 diabetic obese db/db mice are refractory to myocardial ischaemic post
      conditioning in vivo: potential role for Hsp20, F1-ATPase delta and Echs1.
AB  - Ischaemic post-conditioning (PostC) is a clinically relevant cardioprotective
      modality that has been confirmed in many species including human. It remains
      unknown if PostC can still protect heart in Type 2 diabetes, a rapidly growing
      disease in the world. This study investigated the efficacy of PostC in the leptin
      receptor-deficient db/db mice, which possess Type 2 diabetic characteristics
      including obesity, hyperglycaemia and hyperleptinaemia. Adult male C57BL/6J wild
      type (WT) and db/db mice were anaesthetized, mechanically ventilated and
      subjected to left coronary artery occlusion for 30 min. followed by 24 hrs of
      reperfusion. For the PostC groups, the hearts underwent six cycles of 10 sec. of
      reperfusion and 10 sec. of re-occlusion at the onset of reperfusion. The mice
      were sacrificed at the end of 24 hrs reperfusion for infarct size measurement.
      PostC significantly reduced infarct size in WT mice (n = 6/group; P < 0.05), but
      not in the db/db mice. To identify alterations in protein expression by PostC,
      proteomic analyses were performed in the heart samples using two-dimensional
      differential in-gel electrophoresis with three CyDye labelling, followed by mass
      spectrometry. The results show that mitochondrial proteins (F(1)-ATPase gamma and
      Echs1) were down-regulated by PostC in WT heart. Such change was absent in the
      db/db heart. On the other hand, PostC reduced Hsp20 in the diabetic heart. In
      summary, PostC fails to protect Type 2 diabetic mice against ischaemia
      reperfusion injury. The potential protein targets for the loss of PostC may
      include F(1)-ATPase gamma, Echs1 and Hsp20 that could regulate cellular ATP
      consumption/production and defense response to ischaemic stress.

PMID- 21722305
TI  - Regulation of the (pro)renin-renin receptor in cardiac remodelling.
AB  - The (pro)renin-renin receptor [(P)RR] was discovered as an important novel
      component of the renin-angiotensin system (RAS). The functional significance of
      (P)RR is widely studied in renal and vascular pathologies and has sparked
      interest for a potential role in cardiovascular disease. To investigate the role
      of (P)RR in cardiac pathophysiology, we aimed to assess (P)RR regulation in
      adverse cardiac remodelling of the failing heart. In particular, we evaluated the
      expression of (P)RR in different models of heart failure and across different
      species. Significantly increased levels of (P)RR mRNA were found in post
      myocardial infarcted (MI) hearts of rats (1.6-fold, P < 0.05) and mice (5-fold, P
      < 0.01), as well as in transgenic rats with overexpression of the mouse renin
      gene (Ren2) (2.2-fold, P < 0.01). Moreover, we observed a strong increase of
      (P)RR expression in hearts of dilated cardiomyopathy (DCM) patients (5.3-fold, P
      < 0.001). Because none of the tested commercially available antibodies appeared
      to detect endogenous (P)RR, a (P)RR-specific polyclonal antibody was generated to
      study (P)RR protein levels. (P)RR protein levels were significantly increased in
      the post-MI rat heart (1.4-fold, P < 0.05) as compared to controls. Most
      interestingly in DCM patients, a significant 8.7-fold (P < 0.05) increase was
      observed. Thus, protein expression paralleled gene expression. These results
      demonstrate that (P)RR expression is strongly up-regulated both in rodent models
      of heart failure and in the failing human heart, hinting to a potential role for
      (P)RR in cardiac pathophysiology.

PMID- 21722306
TI  - Horizontal root fracture treated with MTA, a case report with a 10-year follow
      up.
AB  - Root fractures occur more frequently in fully erupted permanent teeth with closed
      apices in which the completely formed root is solidly supported in the bone and
      periodontium. The consequences can be complex because of combined damage to the
      pulp, dentine, cementum, bone, and periodontium. Management of horizontal root
      fractures and lateral luxation depends on several factors, with the result that
      various clinical modalities have been suggested. This case report describes the
      treatment and 10-year follow-up of two maxillary central incisors, one with
      horizontal root fracture and the other with lateral luxation, treated with
      mineral trioxide aggregate and root canal treatment, respectively.

PMID- 21722307
TI  - Efficacy of the enamel matrix derivative to induce cementogenesis in vital and
      endodontically treated teeth with osseous dehiscence defects.
AB  - This experiment assessed the efficacy of the enamel matrix derivative (EMD) to
      regenerate cementum in vital and endodontically treated teeth with osseous
      dehiscence defects. Five adult female beagle dogs were used. Thirty maxillary
      teeth (bilateral maxillary canines and second and fourth premolars) were randomly
      divided into two experimental groups (groups A and B, containing 12 teeth each)
      and one control group (group C). Endodontic treatment was only performed on teeth
      in group A compared with teeth in groups B and C. Buccal osseous dehiscence
      defects were surgically created in teeth from all groups. Teeth in the
      experimental group were treated with the EMD, whereas the controls were not.
      After 5 months, the animals were sacrificed and block sections of the teeth in
      experimental and control groups were processed for histological analysis. Newly
      regenerated cementum was observed in all teeth in groups A and B. No cementum
      regeneration was observed in group C. There was a significant difference in
      cementum generation between the experimental and control groups (P < 0.001). EMD
      therapy induces cementogenesis in vital and endodontically treated teeth with
      osseous dehiscence defects.

PMID- 21722308
TI  - Surgical management of recurrent insufficiency of the sapheno-femoral junction
      using modified technique of Junod.

PMID- 21722311
TI  - Biochemistry for tomorrow's medicine. Abstracts of the 36th FEBS Congress.
      Torino, Italy. June 25-30, 2011.

PMID- 21722309
TI  - Endemic systemic mycoses: coccidioidomycosis, histoplasmosis,
      paracoccidioidomycosis and blastomycosis.
AB  - Endemic deep or systemic mycoses are common in specific geographical areas of the
      world. Coccidioidomycosis is present in semi-desert areas, histoplasmosis and
      paracoccidioidomycosis in tropical regions and blastomycosis belongs to temperate
      climates. The two former are widely distributed in the American continent and
      some tropical regions of the world; the third is limited to Central and South
      America, and the last to North America and Central and East Africa. These mycoses
      all have a similar pathogenesis, as the inoculum enters the host through the
      respiratory tract. Cutaneous manifestations are secondary to lymphatic and
      hematogenous dissemination. These deep mycoses are exceptional in Europe. Most
      cases are observed in returning travelers from endemic areas, aid workers,
      archaeologists, speleologist and immigrants. However, there have been some
      autochthonous cases of histoplasmosis due to Histoplasma capsulatum var.
      capsulatum reported in European countries such as Italy and Germany. In this
      article, we provide up-to-date epidemiological, clinical, diagnostic and
      therapeutic data on the four most important imported systemic mycoses in Europe.

PMID- 21722310
TI  - Nodular scabies: hypersensitivity reaction or infection?

PMID- 21722312
TI  - Muramyl-dipeptide-induced mitochondrial proton leak in macrophages is associated
      with upregulation of uncoupling protein 2 and the production of reactive oxygen
      and reactive nitrogen species.
AB  - The synthetic immunomodulator muramyl dipeptide (MDP) has been shown to induce,
      in vivo, mitochondrial proton leak. In the present work, we extended these
      findings to the cellular level and confirmed the effects of MDP in vitro on
      murine macrophages. The macrophage system was then used to analyse the mechanism
      of the MDP-induced mitochondrial proton leak. Our results demonstrate that the
      cellular levels of superoxide anion and nitric oxide were significantly elevated
      in response to MDP. Moreover, isolated mitochondria from cells treated with MDP
      presented a significant decrease in respiratory control ratio, an effect that was
      absent following treatment with a non-toxic analogue such as murabutide.
      Stimulation of cells with MDP, but not with murabutide, rapidly upregulates the
      expression of the mitochondrial protein uncoupling protein 2 (UCP2), and
      pretreatment with vitamin E attenuates upregulation of UCP2. These findings
      suggest that the MDP-induced reactive species upregulate UCP2 expression in order
      to counteract the effects of MDP on mitochondrial respiratory efficiency.

PMID- 21722313
TI  - PRDM1/Blimp1 downregulates expression of germinal center genes LMO2 and HGAL.
AB  - Human germinal center-associated lymphoma (HGAL) and LIM domain only-2 (LMO2) are
      proteins highly expressed in germinal center (GC) B lymphocytes. HGAL and LMO2
      are also expressed in GC-derived lymphomas and distinguish biologically distinct
      subgroups of diffuse large B-cell lymphomas (DLBCL) associated with improved
      survival. However, little is known about their regulation. PRDM1/Blimp1 is a
      master regulator of terminal B cell differentiation and may also function as a
      tumor suppressor in the pathogenesis of DLBCL, where it is frequently inactivated
      by mutations and deletions. We now demonstrate that both HGAL and LMO2 are
      directly regulated by the transcription repressor PRDM1. In vivo studies
      demonstrate that PRDM1 directly binds to the recognition sites within the
      upstream promoters of both HGAL and LMO2. PRDM1 binding suppresses endogenous
      protein and mRNA levels of HGAL and LMO2. In addition, promoter analysis reveals
      that site-specific binding of PRDM1 to the promoters is capable of repressing
      transcriptional activity. This inhibitory effect of PRDM1 suggests that it has a
      key role in the loss of HGAL and LMO2 expression upon differentiation of GC B
      cells to plasma cells and may also contribute to absence of HGAL and LMO2
      expression in post-GC lymphoid tumors.

PMID- 21722314
TI  - Membrane and surface interactions of Alzheimer's Abeta peptide--insights into the
      mechanism of cytotoxicity.
AB  - Alzheimer's disease is the most common form of dementia and its pathological
      hallmarks include the loss of neurones through cell death, as well as the
      accumulation of amyloid fibres in the form of extracellular neuritic plaques.
      Amyloid fibrils are composed of the amyloid-beta peptide (Abeta), which is known
      to assemble to form 'toxic' oligomers that may be central to disease pathology.
      Abeta is produced by cleavage from the amyloid precursor protein within the
      transmembrane region, and the cleaved peptide may retain some membrane affinity.
      It has been shown that Abeta is capable of specifically binding to phospholipid
      membranes with a relatively high affinity, and that modulation of the composition
      of the membrane can alter both membrane-amyloid interactions and toxicity.
      Various biomimetic membrane models have been used (e.g. lipid vesicles in
      solution and tethered lipid bilayers) to examine the binding and interactions
      between Abeta and the membrane surfaces, as well as the resulting permeation.
      Oligomeric Abeta has been observed to bind more avidly to membranes and cause
      greater permeation than fibrillar Abeta. We review some of the recent advances in
      studying Abeta-membrane interactions and discuss their implications with respect
      to understanding the causes of Alzheimer's disease.

PMID- 21722315
TI  - Critical care nurses' knowledge about pressure ulcer in southeast of Iran.
AB  - Pressure ulcer prevention needs nurses' awareness of sore classification/onset,
      its item characteristics, and its prevention. Using Pieper's Pressure Ulcer
      Knowledge Test, 126 critical care nurses' knowledge about pressure ulcer was
      examined. The questionnaire was divided into three categories including: (1) sore
      classification/onset; (2) wound characteristics, and (3) preventive measure. The
      level of nurse's knowledge was insufficient. The highest rate of correct answers
      belonged to section 2 - prevention of pressure ulcer. Programs aimed at raising
      nurses' knowledge accompanied by interventions intended to decrease incidence of
      pressure ulcer are important parts in educational programs. Continuing education
      may need to be added to the pressure ulcer care to improve the quality of care at
      intensive care units.

PMID- 21722316
TI  - Hospital-acquired pressure ulcers in two Swedish County Councils: cross-sectional
      data as the foundation for future quality improvement.
AB  - The objectives of the study were to examine the prevalence of pressure ulcers and
      hospital-acquired pressure ulcers (HAPU) and identify modifiable factors in
      patients who develop HAPU as the basis for subsequent quality assurance studies
      and improvement in hospital care. The study was conducted in five hospitals in
      two Swedish County Councils. A 1-day prevalence study (n = 1192) using the
      standards of the European Pressure Ulcer Advisory Panel and Collaborative
      Alliance for Nursing Outcomes was conducted. The prevalence of ulcers was 14.9%
      and 11.6% were HAPU. Older age, more days of hospitalisation, less activity,
      problems with shear and friction and reduced sensory perception contributed
      significantly to HAPU. Pressure ulcer prevention strategies used more often in
      those with HAPU were risk assessment at admission, provision of a pressure relief
      mattress, having a turning schedule and using a heel or chair cushion. The
      prevalence of pressure ulcers continues to be a significant issue in acute care
      and the prevalence of HAPU is high. There is significant room for quality
      improvement in pressure ulcer prevention in Swedish hospitals. Future research
      needs to address both HAPU and community-acquired pressure ulcers and focus on
      preventive strategies, including when they are initiated and which are effective
      in mitigating the high HAPU rate.

PMID- 21722317
TI  - Wound healing effect of Haruan (Channa striatus) spray.
AB  - Haruan (Channa striatus) is a type of fresh water fish in Malaysia that is known
      to promote wound healing. Haruan water extract has been formulated in an aerosol
      system which can produce a film for wound dressing. As topical preparation,
      Haruan spray needs to be evaluated in terms of the possibility to cause
      irritation reaction or toxic response. Three experiments were carried out to
      evaluate the safety of Haruan spray which are Primary Skin Irritation test,
      Intracutaneous test and Systemic Injection test. The result shows that Haruan
      spray gave no significant responses to all the above tests. The investigation of
      the effect of Haruan spray as wound dressing in the healing process was performed
      in Sprague-Dawley rats where 6-cm long full-thickness incision wound and burn
      wound were made on the back of the animals. Haruan spray was tested and compared
      with blank formula as control. Tensile strength test of treated wound was carried
      out at the 3rd, 6th, 9th and 12th day after wounding and treatment. The burn
      wounds contraction was measured daily for 21 days. Results showed that haruan
      water extract spray formula is not only effective but also safe for application
      to both incision and burn wounds.

PMID- 21722318
TI  - Dz13: c-Jun downregulation and tumour cell death.
AB  - DNAzymes (DNA enzymes and deoxyribozymes) are synthetic, single-stranded DNA
      based catalysts engineered to bind to their complementary sequence in a target
      messenger RNA (mRNA) through Watson-Crick rules for base-pairing and cleave the
      mRNA at predetermined phosphodiester linkages. Dz13, a DNAzyme that cleaves c-Jun
      mRNA, has been found to have efficacious effects against tumours directly,
      activity against tumour-induced angiogenesis, inhibition of neointima formation
      after arterial injury and control of inflammatory responses. Recent studies in
      endothelial cells demonstrate that the off-target effects of Dz13 may in fact be
      driving some of these potentially therapeutic effects, although no mechanisms
      have been clearly defined in tumour cells. Recent data show that Dz13 is capable
      of inhibiting more types of tumours and potently induces apoptosis in a panel of
      tumour cell lines. Hand-in-hand with in vivo testing, Dz13 has been formulated
      into a biocompatible nanoparticle, enabling its full potential to be realized.
      Its chemistry is partly responsible for its activity against tumour cells, but it
      is safe to use in vivo and surprisingly shows little harmful effects against
      normal cells. These findings provide hope that Dz13 may be useful clinically for
      the treatment of a variety of cancers.

PMID- 21722319
TI  - Safety and efficacy of new 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
      analogs as potential phosphodiesterase-4 inhibitors in NIH-3T3 mouse fibroblastic
      cells.
AB  - A novel series of potential phosphodiesterase-4 (PDE-4) inhibitors, 6-(3
      (cyclopentyloxy)-4-methoxyphenyl)-3-aryl-7H-[1,2,4]triazolo[3,4
      b][1,3,4]thiadiazines, were developed. Different concentrations of the
      synthesized compounds were tested on cultured NIH-3T3 cells to determine their
      safety and efficacy in NIH-3T3 mouse fibroblastic cells in comparison with
      rolipram, a selective PDE-4 inhibitor. The viability of cells was determined by
      (3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide (MTT) assay. The
      PDE inhibition rate was measured indirectly by determination of concentrations of
      extracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine
      monophosphate (cGMP) using enzyme-linked immunoassay technique. The results
      showed that all tested compounds caused a marked increase in the concentration of
      cAMP, whereas the concentration of cGMP stayed approximately unchanged. The
      cytotoxic IC(50) of all synthesized compounds was approximately twofold greater
      than their required concentration for inhibition of PDE-4 (in terms of elevation
      of cAMP), and thus, these structures could be used to develop potent and safe
      inhibitors of PDE-4 enzyme.

PMID- 21722320
TI  - 3D-QSAR studies of JNK1 inhibitors utilizing various alignment methods.
AB  - We report our three-dimensional quantitative structure activity relationship (3D
      QSAR) studies of the series of anilinopyrimidine derivatives of JNK1 inhibitors.
      The comparative molecular field analysis (CoMFA) and comparative molecular
      similarity indices analysis (CoMSIA) were applied using different alignment
      methods. The ligand-based atom-by-atom matching alignment has produced better
      values for CoMFA (q(2) = 0.646 and r(2) = 0.983), while in CoMSIA it has achieved
      only lower statistical values. The pharmacophore-based model has produced (q(2) =
      0.568, r(2) = 0.938) and (q(2) = 0.670, r(2) = 0.982) for CoMFA and CoMSIA
      models, respectively. As the model was based on the receptor-guided alignment,
      all the compounds were optimized within the receptor, resulting in q(2) = 0.605
      and r(2) = 0.944 for CoMFA, and q(2) = 0.587 and r(2) = 0.863 for CoMSIA.
      Molecular Dynamic simulation studies suggested that the generated models were
      consistent with the low-energy protein ligand conformation. The CoMFA and CoMSIA
      contour maps indicated that the substitutions of the electropositive groups in
      the phenyl ring, and an addition of hydrophobic groups in the pyrimidine ring,
      are important to enhance the activity of this series. Moreover, the virtual
      screening analysis against NCI database yields potentials hits, and the results
      obtained would be useful to synthesize selective and highly potent c-Jun N
      terminal kinase 1 analogs.

PMID- 21722321
TI  - A short history of physiology.

PMID- 21722322
TI  - Bathing residents with dementia in long-term care: critical incidents described
      by personal support workers.
AB  - AIM AND OBJECTIVE: The aim of this study was to describe and gain insight into
      the critical incidents depicted by personal support workers (PSWs) in long-term
      care (LTC) related to bathing residents who have dementia. BACKGROUND: Residents
      with dementia in LTC often display responsive/protective behaviours during
      bathing. Consequently, bathing is a source of stress for PSWs who provide most of
      the personal care for LTC residents in Ontario, Canada. DESIGN: A qualitative
      descriptive study employing the critical incident technique (CIT) was used.
      METHOD: Eight PSWs were interviewed and 24 incidents were collected and analyzed
      using thematic content analysis. RESULTS: Findings revealed that PSWs experience
      the following during bathing: managing responsive/protective behaviours, working
      with limited resources, and dealing with communication difficulties. Participants
      used various strategies to respond to these challenges; however, they reported
      limited strategies to manage the most challenging behaviours. CONCLUSIONS: Many
      of the bathing strategies described by the PSWs in this study are found in the
      literature about best bathing practices in dementia care. However, it is evident
      that further work is needed to support PSWs to manage the most difficult physical
      responsive/protective behaviours that occur during bathing. IMPLICATIONS FOR
      PRACTICE: This study has clear implications for knowledge translation.

PMID- 21722323
TI  - Bedrails and vulnerable older adults: how should nurses make 'safe and sound'
      decisions surrounding their use?
AB  - AIM AND OBJECTIVES: This paper examines the available evidence and uses ethical
      principles to answer how nurses should make safe and sound decisions surrounding
      the use of bedrails. BACKGROUND: Bedrails are frequently observed in practice.
      They are designed as safety devices but there is evidence of indiscriminate and
      misuse with vulnerable adults. METHODS: The OVID MEDLINE, BNI and CINAHL
      databases were searched using key words dignity or autonomy and old[er] or
      elder[s/ly]), people, adult[s], patient[s], client[s] or user[s], and bed rails,
      bed guards, cot sides or side rails (and associated variations). Additionally
      United Kingdom legislation, professional codes of practice and national patient
      safety agency resources were also searched. RESULTS:   Bedrail use needs careful
      consideration. The published evidence can be confusing and contradictory. Nurses
      have a duty to provide care which promotes respect for patient's autonomy,
      integrity and dignity for which individualised assessment is essential.
      Additionally overt consideration of beneficence, non-maleficence and justice
      supports decision making. CONCLUSIONS: Protection and promotion of respect for
      autonomy, integrity and dignity especially with older adults must be evidenced in
      practice. The use of an ethical framework can enable nurses to make transparent
      and defensible decisions about the appropriate use of bedrails, thereby
      fulfilling professional, moral, and legal requirements. IMPLICATIONS FOR
      PRACTICE: Bedrail use has implications beyond falls prevention. Protection and
      promotion of respect for autonomy, integrity and dignity with older adults must
      be considered in decision-making. Physical safety must be assessed as part of a
      holistic assessment. Nurses may need support and training to ensure 'safe and
      sound' surrogate decision-making in practice.

PMID- 21722324
TI  - Low hemoglobin density potential marker of iron availability.
AB  - INTRODUCTION: Low hemoglobin density (LHD%) is a new parameter provided by
      Beckman-Coulter derived from the mean cell hemoglobin concentration, using the
      mathematical sigmoid transformation LHD% = 100*?(1-(1/(1 + e(1.8(30-MCHC)))).
      This study investigated the reliability of LHD% for the assessment of iron status
      in the presence of inflammation. METHODS: Healthy subjects (n = 90) and patients
      with iron deficiency (IDA, n = 110), chronic kidney disease (CKD, n = 65) and
      anemia of chronic disease (ACD, n = 85; 24 were iron deficient and 61 were iron
      sufficient) were analyzed on a LH 780 analyzer (Beckman Coulter Inc., Miami, FL,
      USA). Independent samples U test and receiver operating characteristic (ROC)
      curve analysis were applied. To determine the concordance between LHD% and
      soluble transferrin receptor (sTrR) Cohen's kappa index was calculated. RESULTS:
      LHD % values showed no statistical difference in patients with IDA and patients
      with ACD accompanied with IDA (P = 0.6427); LHD% values in these patients were
      significantly different (P < 0.0001) compared with the iron-sufficient patients
      with ACD. ROC analysis for LHD% in the detection of iron deficiency showed the
      following: area under curve 0.903; cut off 5.5%, sensitivity 88.6%, specificity
      76.9%; kappa index, 0.65. CONCLUSION: LHD% is a reliable parameter for the
      detection of iron deficiency in patients with anemia in the presence of
      inflammation.

PMID- 21722325
TI  - Platelet activation, coagulation activation and C-reactive protein in
      simultaneous samples from the vascular access and peripheral veins of
      haemodialysis patients.
AB  - INTRODUCTION: Most studies of haemodialysis (HD) patients compare venous blood
      samples from controls with samples from the vascular access (VA) of HD patients.
      We hypothesised that VA samples may be more prothrombotic compared with venous
      samples. METHODS: Samples were taken simultaneously from the VA and the
      contralateral antecubital vein, from 26 patients immediately before HD. Platelet
      function was assessed by (1) flow cytometric measurement of P-selectin expression
      and fibrinogen binding (+/-ADP) and 2) Ultegra rapid platelet function assay.
      Plasma soluble P-selectin, von Willebrand factor antigen, high sensitivity C
      reactive Protein (hs-CRP), thrombin-antithrombin III complex and D-dimer measured
      by ELISA. RESULTS: Thrombin receptor activating peptide-induced platelet
      aggregation (P < 0.001) and hs-CRP (P < 0.001) were higher in VA compared with
      venous samples. Unstimulated platelet fibrinogen binding (P = 0.016) and ADP
      stimulated P-selectin expression (P = 0.008) were lower in VA compared with
      venous samples. The significant difference in hsCRP persisted when patients
      taking and not taking antiplatelet therapy were analysed separately, but platelet
      activation remained significantly different only in the nonantiplatelet group.
      CONCLUSION: There are statistically significant differences between sampling
      sites, although samples from the VA do not appear to be more pro-thrombotic.
      Future studies comparing HD patients with controls should ensure uniformity of
      sampling sites to prevent inaccurate conclusions being drawn.

PMID- 21722326
TI  - Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in
      streptozotocin-induced experimental diabetes in rats.
AB  - BACKGROUND: Most of the currently available oral hypoglycemic drugs for the
      treatment of diabetes mellitus elicit detrimental side effects. Hence, the search
      for plant-derived products for the treatment of diabetes continues. Gossypin, a
      pentahydroxy flavone glucoside found in the flowers of Hibiscus vitifolius, has
      many biological properties, including as an antioxidant, anti-inflammatory and
      anticancer agent. The aim of the present study was to evaluate the effect of
      gossypin in streptozotocin (STZ)-induced experimental diabetes in rats. METHODS:
      Diabetic rats were administered 20 mg/kg per day gossypin orally for 30 days. On
      the 28th day, rats were subjected to an oral glucose tolerance test. In addition,
      blood glucose, plasma insulin, hemoglobin, and HbA1c levels were determined, as
      was the glycogen content of the liver and muscles. Plasma protein and blood urea
      were also estimated. RESULTS: Oral administration of gossypin to diabetic rats
      resulted in improved glucose tolerance. Increased blood glucose and HbA1c levels
      and the reduced plasma insulin and hemoglobin levels in diabetic rats were
      significantly reversed to near normal after oral administration of gossypin.
      Furthermore, the glycogen content of the liver and muscles was significantly
      improved after gossypin treatment of diabetic rats, and plasma protein and blood
      urea levels were almost normalized. The data obtained in gossypin-treated rats
      were comparable with those obtained following gliclazide treatment of rats, a
      standard reference drug for diabetes. CONCLUSIONS: The results of the present
      study indicate that gossypin has potent antidiabetic activity in STZ-induced
      experimental diabetes in rats.

PMID- 21722327
TI  - DNA barcoding of the recently evolved genus Holcoglossum (Orchidaceae:
      Aeridinae): a test of DNA barcode candidates.
AB  - Orchidaceae is one of the largest families of flowering plants. Many species of
      orchid are endangered, and all species are included in Conventions on
      International Trade of Endangered Species of Fauna and Flora (CITES) I and II,
      but it is very difficult to identify orchid species, even those with fertile
      parts. The genus Holcoglossum (Orchidaceae: Aeridinae) has long been problematic
      in taxonomy. It consists of both long-evolved and radiated species and is an
      excellent case to use for testing DNA barcodes for Orchidaceae. We investigated
      the power of a subset of proposed plant barcoding loci [rbcL, matK, atpF-atpH,
      psbK-psbI, trnH-psbA and internal transcribed spacer (ITS)] to discriminate
      between species in this genus. Our results showed that all these DNA regions,
      except psbK-psbI and atpF-atpH, can be amplified easily from Holcoglossum and
      sequenced with established primers. The DNA regions matK and ITS had the highest
      variability. Among the six loci, matK resolved eight of the 12 Holcoglossum
      species and had the highest discriminatory ability. However, the combination of
      matK and ITS showed a greater ability to identify species than matK alone. Single
      or combined DNA markers discriminated between Holcoglossum species distributed in
      tropical areas effectively, but had less ability to identify radiated species
      from the temperate Hengduan Mountains of China. In the study, matK proved to be a
      useful DNA barcode for the genus Holcoglossum; however, complementary DNA regions
      are still required to accelerate the investigation and preservation of radiated
      species of orchid.

PMID- 21722328
TI  - Identification of DNA repair gene Ercc1 as a novel target in melanoma.
AB  - Increased expression of DNA repair genes contributes to the extreme resistance
      shown by melanoma to conventional DNA-damaging chemotherapeutics. One such
      chemotherapeutic effective against a range of other cancers, but not melanoma, is
      cisplatin. The DNA repair protein, ERCC1, is needed to remove cisplatin-induced
      DNA damage. We have shown that ERCC1 is essential for melanoma growth and
      resistance to cisplatin in a mouse xenograft model. Untreated xenografts of our
      transformed Ercc1-proficient melanocyte cell line grew very rapidly as malignant
      melanoma. Cisplatin treatment caused initial shrinkage of xenografts, but
      cisplatin-resistant regrowth soon followed. Cells reisolated into culture had
      twofold elevated levels of ERCC1 compared to both input cells and cells
      reisolated from untreated xenografts. An isogenic Ercc1-deficient derivative grew
      equally well in vitro as the Ercc1-proficient melanocyte cell line. However, in
      xenografts, the Ercc1-deficient melanomas were much slower to establish and were
      completely cured by just two cisplatin treatments.

PMID- 21722329
TI  - Clustering of and risk factors for the porcine high fever disease in a region of
      Vietnam.
AB  - Porcine high fever disease (PHFD) emerged in 2006 in China and spread to Vietnam.
      Little work has been carried out to investigate PHFD risk factors and space-time
      dynamics. To fill this gap, we investigated probable cases of PHFD at household
      level as the outcome. A study area, approximately 100 sq. km, was selected from a
      province of southern Vietnam that had reported the outbreak of PHFD in 2008. A
      survey was conducted in the study area to collect information about swine health
      problems during 2008. The questionnaire included three sections: general
      information, clinical signs of disease in pigs and production factors believed to
      be risk factors. Cases were defined at the household level and included
      interpretation of clinical signs in series. Logistic regression with a random
      intercept at the hamlet level was used to assess risk factors for PHFD at the
      household level. Spatial clustering was investigated using the D-function and a
      Cuzick-Edward's test. Spatial clusters were evaluated using a spatial relative
      risk surface and the spatial scan statistic using a Bernoulli model. Space-time
      clustering was explored using a space-time K-function and Knox's test. Space-time
      clusters were evaluated using a space-time permutation model in SaTScan. Of 955
      households with questionnaire data, 33.4% were classified as cases. The
      statistical significance of space and space-time clustering differed between
      methods employed. The risk factors associated with occurrence of cases were
      higher numbers of sows and finishing pigs (log 2 transformed), receiving pigs
      from an external source and the interaction between using 'water green crop'
      (WGC) as pig feed and owning ducks with or without direct contact with pigs. The
      interaction between the presence of ducks and feeding WGC to pigs suggested the
      involvement of pathogens that might be present in water (environment) and could
      further replicate in or on ducks.

PMID- 21722330
TI  - Conditions in subjects with rheumatic diseases: pulmonary manifestations of
      vasculitides.
AB  - Pulmonary involvement is a common complication of vasculitides, especially small
      vessel vasculitides. This review provides an overview of vasculitic
      manifestations of the lung as well as of other organs involved in vasculitides.
      Furthermore, it provides the diagnostic procedures required to asses a patient
      with vasculitic lung involvement and gives an overview of current treatment
      strategies.

PMID- 21722331
TI  - Cardiovascular co-morbidity in patients with rheumatic diseases.
AB  - During recent years atherosclerosis, the major cause of cardiovascular disease
      (CVD), has been recognised as a chronic inflammatory condition in which rupture
      of atherosclerotic lesions appears to play a major role. The risk of CVD is
      raised in many rheumatic diseases. This risk is high in systemic lupus
      erythematosus - as much as a 50-times increase among middle-aged women has been
      reported. Studies on CVD and atherosclerosis in rheumatic disease could thus
      provide interesting information about CVD and atherosclerosis in addition to
      being an important clinical problem. A combination of traditional and
      nontraditional risk factors accounts for the increased risk of CVD and
      atherosclerosis in rheumatic disease. One interesting possibility is that
      atherosclerotic lesions in rheumatic disease are more prone to rupture than
      normal atherosclerotic lesions. It is also likely that increased risk of
      thrombosis may play an important role, not least in systemic lupus erythematosus.
      Further, it is not clear whether an increased risk of CVD is a general feature of
      rheumatic disease, or whether this only occurs among subgroups of patients. It
      should be emphasised that there is an apparent lack of treatment studies where
      CVD in rheumatic disease is the end point. Control of disease activity and of
      traditional risk factors, however, appears to be well founded in relation to CVD
      in rheumatic disease. Further studies are needed to determine the exact role of
      lipid-lowering drugs as statins. Hopefully novel therapies can be developed that
      target the causes of the inflammation in atherosclerotic lesions both in
      rheumatic patients and in the general population.

PMID- 21722332
TI  - Liver involvement in subjects with rheumatic disease.
AB  - The liver is often overlooked as a target organ, with pathology either secondary
      to an underlying disease or due to the toxicity of therapies and the medical
      complications of extrahepatic diseases. It is thus important for the clinical
      rheumatologist to be aware of the diagnostic procedure to monitor liver injury.
      Indeed, systemic rheumatologic diseases may be associated with liver
      abnormalities secondary to the presence of a coexisting autoimmune liver disease
      (particularly primary biliary cirrhosis or autoimmune hepatitis), the direct
      involvement of the liver parenchyma, or the impact of medical treatments
      (particularly methotrexate) on the liver. In addition, the rheumatologist should
      be aware of the impact of immunosuppressive agents on underlying viral
      infections, particularly viral hepatitis. We review herein the data on the role
      of the liver in the clinical management of systemic rheumatic diseases.

PMID- 21722333
TI  - How to assess the dangers of hyperoxemia: methodological issues.

PMID- 21722334
TI  - Supplementary oxygen for nonhypoxemic patients: O2 much of a good thing?
AB  - Supplementary oxygen is routinely administered to patients, even those with
      adequate oxygen saturations, in the belief that it increases oxygen delivery. But
      oxygen delivery depends not just on arterial oxygen content but also on
      perfusion. It is not widely recognized that hyperoxia causes vasoconstriction,
      either directly or through hyperoxia-induced hypocapnia. If perfusion decreases
      more than arterial oxygen content increases during hyperoxia, then regional
      oxygen delivery decreases. This mechanism, and not (just) that attributed to
      reactive oxygen species, is likely to contribute to the worse outcomes in
      patients given high-concentration oxygen in the treatment of myocardial
      infarction, in postcardiac arrest, in stroke, in neonatal resuscitation and in
      the critically ill. The mechanism may also contribute to the increased risk of
      mortality in acute exacerbations of chronic obstructive pulmonary disease, in
      which worsening respiratory failure plays a predominant role. To avoid these
      effects, hyperoxia and hypocapnia should be avoided, with oxygen administered
      only to patients with evidence of hypoxemia and at a dose that relieves hypoxemia
      without causing hyperoxia.

PMID- 21722335
TI  - ICU survival and the central to mixed venous oxygen difference.

PMID- 21722336
TI  - The lung and the brain: a dangerous cross-talk.
AB  - Brain or lung injury or both are frequent causes of admission to intensive care
      units and are associated with high morbidity and mortality rates. Mechanical
      ventilation, which is commonly used in the management of these critically ill
      patients, can induce an inflammatory response, which may be involved in distal
      organ failure. Thus, there may be a complex crosstalk between the lungs and other
      organs, including the brain. Interestingly, survivors from acute lung
      injury/acute respiratory distress syndrome frequently have some cognitive
      deterioration at hospital discharge. Such neurologic dysfunction might be a
      secondary marker of injury and the neuroanatomical substrate for downstream
      impairment of other organs. Brainlung interactions have received little attention
      in the literature, but recent evidence suggests that both the lungs and brain can
      promote inflammation through common mediators. The present commentary discusses
      the main physiological issues related to brain-lung interactions.

PMID- 21722337
TI  - Measurement of monocyte apoptosis, plasma IL-1beta and PR3 activity as an
      approach to evaluate the immunological status in sepsis.

PMID- 21722338
TI  - The earthquake and tsunami--observations by Japanese physicians since the 11
      March catastrophe.
AB  - Japan was struck by a magnitude 9.0 earthquake and a tsunami on 11 March 2011.
      Although this catastrophe has caused the most devastating damage to Japan since
      World War II, we believe that our systematic preparation for disasters somewhat
      alleviated the damage. Learning lessons from the magnitude 7.3 Great Hanshin
      earthquake in 1995, the government organized approximately 700 medical teams
      specialized in disaster management. In this earthquake of 2011, hundreds of
      medical teams were successfully deployed and started operations within the first
      72 hours. Furthermore, the internet, which was not commonly used in 1995, made
      significant contributions in communication among clinicians and enabled them to
      promptly identify the needs of the affected hospitals. In addition, medical
      professional societies took leadership in the logistics of transferring victims
      away from the disaster zone. We also observed that the spectrum of causes of
      death is distinct between the earthquakes of 1995 and 2011. In 1995, many victims
      died from trauma, including crash injury, and delays in providing hemodialysis
      contributed to additional deaths. In 2011, in contrast, many victims died from
      drowning in the tsunami, and most survivors did not have life-threatening
      injuries.

PMID- 21722339
TI  - Fibromyalgia, myofascial pain, tender points and trigger points: splitting or
      lumping?
AB  - Myofascial trigger points (MTPs) have long been a contentious issue in relation
      to fibromyalgia, and poorly defined pain complaints in general. Can MTPs be
      reproducibly identified? Do MTPs have valid objective findings, such as
      spontaneous electromyographic activity, muscle microdialysis evidence for an
      inflammatory milieu or visualization with newer ultrasound techniques? Is
      fibromyalgia a syndrome of multiple MTPs, or is focal muscle tenderness a
      manifestation of central sensitization? These issues are discussed with relevance
      to a recent paper reporting that manual palpation of active MTPs elicits the
      spontaneous pain experienced by fibromyalgia patients.

PMID- 21722340
TI  - Risky business.

PMID- 21722341
TI  - Renal co-morbidity in patients with rheumatic diseases.
AB  - Renal co-morbidity is common in patients with rheumatic disease based on regular
      assessment of serum and urine parameters of renal function. When patients present
      with both arthritis and renal abnormalities the following questions have to be
      addressed. Is kidney disease a complication of rheumatic disease or its
      management, or are they both manifestations of a single systemic autoimmune
      disease? Is rheumatic disease a complication of kidney disease and its
      management? How do rheumatic disease and kidney disease affect each other even
      when they are unrelated? The present review provides an overview of how to
      address these questions in daily practice.

PMID- 21722342
TI  - Treating rheumatic patients with a malignancy.
AB  - Management of patients with inflammatory rheumatic disease and a history of (or
      even a current) malignant disease poses some particular challenges. As direct
      evidence of the risk of (recurrent or de novo) malignancy in patients with a
      history of malignant disease is scarce, such a risk may be estimated indirectly
      from the principal carcinogenicity of the respective drug to be used or (also
      indirectly) from cancer reactivation data from the transplant literature. In
      general, cancer risk is increased in patients receiving combination
      immunosuppressive treatment, but the risk in patients receiving individual drugs
      (with the exception of alkylating agents) remains entirely unclear. Indirect
      evidence supports the intuitive concept that the risk of cancer decreases over
      time after a successful cancer treatment. The only two studies in rheumatic
      patients with a cancer history were small and have not been able to show an
      increase in cancer reactivation. The risk of reactivation also depends on the
      site and location of the prior malignancy. In conclusion, the decision to treat a
      patient with a history of cancer immunosuppressively should be shared by the
      rheumatologist and the oncologist. Once the decision is established, such
      patients need intensive and close monitoring.

PMID- 21722343
TI  - Considering comorbidity in managing rheumatic diseases: going where trials cannot
      go.

PMID- 21722345
TI  - Epidermal stem cell dynamics.
AB  - Wong and Reiter have explored the possibility that hair follicle stem cells can
      give rise to basal cell carcinoma (BCC). They expressed in mice an inducible
      human BCC-derived oncogenic allele of Smoothened, SmoM2, under the control of
      either the cytokeratin 14 (K14) or cytokeratin 15 (K15) promoter. Smoothened
      encodes a G-protein-coupled receptor protein in the hedgehog pathway, the
      misregulation of which is implicated in BCC and other human cancers. Chronic
      injury is thought to be a contributing factor. The authors used K14 as a marker
      for stem cells in the basal layer of the epidermis and K15 as a marker for
      epidermal stem cells in the bulge of hair follicles. Upon activation, K14
      construct-bearing mice readily formed BCC-like tumours, whereas this was not the
      case in K15:SmoM2-carrying mice. Upon wounding the epidermis, however, there was
      widespread BCC-like tumour formation in the skin of K15:SmoM2 mice. The authors
      conclude that wounding recruited bulge epidermal stem cells to the surface,
      allowing the cells to escape quiescence in the stem cell niche and to arrive in
      an environment where the hedgehog pathway becomes activated and therefore
      tumorigenesis is elicited. While this is a provocative result and the authors'
      conclusion may well be correct, there are alternative explanations.

PMID- 21722344
TI  - The role of p21 in regulating mammalian regeneration.
AB  - The MRL (Murphy Roths Large) mouse has provided a unique model of adult mammalian
      regeneration as multiple tissues show this important phenotype. Furthermore, the
      healing employs a blastema-like structure similar to that seen in amphibian
      regenerating tissue. Cells from the MRL mouse display DNA damage, cell cycle G2/M
      arrest, and a reduced level of p21CIP1/WAF. A functional role for p21 was
      confirmed when tissue injury in an adult p21-/- mouse showed a healing phenotype
      that matched the MRL mouse, with the replacement of tissues, including cartilage,
      and with hair follicle formation and a lack of scarring. Since the major
      canonical function of p21 is part of the p53/p21 axis, we explored the
      consequences of p53 deletion. A regenerative response was not seen in a p53-/-
      mouse and the elimination of p53 from the MRL background had no negative effect
      on the regeneration of the MRL.p53-/- mouse. An exploration of other knockout
      mice to identify p21-dependent, p53-independent regulatory pathways involved in
      the regenerative response revealed another significant finding showing that
      elimination of transforming growth factor-beta1 displayed a healing response as
      well. These results are discussed in terms of their effect on senescence and
      differentiation.

PMID- 21722346
TI  - Mitochondrial therapeutics in Alzheimer's disease and Parkinson's disease.
AB  - In neurons, mitochondria serve a wide variety of processes that are integral to
      their function and survival. It is, therefore, not surprising that evidence of
      mitochondrial dysfunction is observed across numerous neurodegenerative diseases.
      Alzheimer's disease and Parkinson's disease are two such diseases in which
      aberrant mitochondrial activity is proposed to contribute to pathogenesis.
      Current therapies for each disease target various mechanisms, but few, if any,
      directly target improved mitochondrial function. Recent discoveries pertaining to
      mitochondrial dynamics reveal that regulation of mitochondrial fission and fusion
      may play a key role in the pathogenesis of these diseases and consequently could
      be novel future therapeutic targets.

PMID- 21722347
TI  - The jigsaw puzzle of our African ancestry: unsolved, or unsolvable?
AB  - A revised root for the Y chromosome phylogeny further fragments the picture of
      modern human origins that can be reconstructed from genetic, linguistic and
      archaeological data.

PMID- 21722348
TI  - Are enrollment sites the key to optimizing participation in genetic studies?
AB  - In a time when the challenge of people being over-researched and experiencing
      research fatigue is increasingly discussed, low participation rates and potential
      sample biases are a growing concern in genetic research. In a recent study
      assessing factors relevant to successful recruitment of patients with myocardial
      infarction to a genetic study, enrollment site was identified as the most
      important factor associated with patient participation, whereas patient-level
      factors such as race, gender and education played a limited or no role. These
      results underline the importance of appropriate recruitment routines at
      enrollment sites in order to reach high levels of participation in genetic
      research.See research article: http://genomemedicine.com/content/3/6/39.

PMID- 21722349
TI  - The tubby family proteins.
AB  - The tubby mouse shows a tripartite syndrome characterized by maturity-onset
      obesity, blindness and deafness. The causative gene Tub is the founding member of
      a family of related proteins present throughout the animal and plant kingdoms,
      each characterized by a signature carboxy-terminal tubby domain. This domain
      consists of a beta barrel enclosing a central alpha helix and binds selectively
      to specific membrane phosphoinositides. The vertebrate family of tubby-like
      proteins (TULPs) includes the founding member TUB and the related TULPs, TULP1 to
      TULP4. Tulp1 is expressed in the retina and mutations in TULP1 cause retinitis
      pigmentosa in humans; Tulp3 is expressed ubiquitously in the mouse embryo and is
      important in sonic hedgehog (Shh)-mediated dorso-ventral patterning of the spinal
      cord. The amino terminus of these proteins is diverse and directs distinct
      functions. In the best-characterized example, the TULP3 amino terminus binds to
      the IFT-A complex, a complex important in intraflagellar transport in the primary
      cilia, through a short conserved domain. Thus, the tubby family proteins seem to
      serve as bipartite bridges through their phosphoinositide-binding tubby and
      unique amino-terminal functional domains, coordinating multiple signaling
      pathways, including ciliary G-protein-coupled receptor trafficking and Shh
      signaling. Molecular studies on this functionally diverse protein family are
      beginning to provide us with remarkable insights into the tubby-mouse syndrome
      and other related diseases.

PMID- 21722350
TI  - Genomes of uncultured eukaryotes: sorting FACS from fiction.
AB  - A recent study explores the genome content of uncultured unicellular marine
      eukaryotes and provides insights about interactions between uncultured eukaryotes
      and other biological entities.

PMID- 21722351
TI  - Hyperoxia after cardiac arrest may not increase ischemia-reperfusion injury.
AB  - In the last decade, moderate hypothermia has become the mainstay of treatment in
      the post-resuscitation period. However, for the damaged brain, optimizing oxygen
      transport, including arterial oxygenation, may also be important. The current
      view states that hyperoxia in the immediate post-resuscitation period may worsen
      cerebral outcome, and international guidelines recommend a target arterial oxygen
      saturation of 94% to 98%. An article in the previous issue of Critical Care
      challenges this viewpoint. In an elegant study using a Cox proportional hazards
      model combined with sensitivity analyses and time period matching, the authors
      show no independent association between hyperoxia and in-hospital mortality. The
      present commentary discusses these contradictory findings and suggests a
      practical solution to solve these differences.

PMID- 21722352
TI  - IL-17 in spondyloarthritis: is the T-party over?
AB  - The past decade has witnessed significant progress in revealing an important role
      for IL-17 in the pathogenesis of several immune-mediated inflammatory diseases.
      Recent studies have provided new insights into the cellular source of IL-17,
      originally identified as the signature cytokine of a distinct CD4(+) T-cell
      subset known as Th17. Accumulating evidence suggests that the majority of the IL
      17 released in inflammatory arthritis is produced by innate immune cells rather
      than T cells. Understanding molecular mechanisms behind these early innate immune
      responses will be the key to designing rational therapies targeting these
      important inflammatory pathways.

PMID- 21722353
TI  - The mouse genetics toolkit: revealing function and mechanism.
AB  - Large-scale projects are providing rapid global access to a wealth of mouse
      genetic resources to help discover disease genes and to manipulate their
      function.

PMID- 21722354
TI  - The use of erlotinib in daily practice: a study on adherence and patients'
      experiences.
AB  - BACKGROUND: Adherence to pharmacological therapy is a complex and multi-factorial
      issue that can substantially alter the outcome of treatment. It has been shown
      that cancer patients, especially when using long-term medication, have similar
      adherence rates to those of patients with other diseases. The consequences of
      poor adherence are poor health outcomes and increased health care costs. Only few
      studies have focused on the use of oral anticancer agents in daily practice.
      Information about the reasons for non-adherence is essential for the development
      of interventions that may increase adherence. This paper presents the CAPER
      erlotinib protocol, which is designed to study the relationship between adherence
      to erlotinib and both the plasma concentration and side-effects in patients with
      NSCLC. Further, the relationships between patient characteristics, disease
      characteristics, side-effects, quality of life, patient beliefs and attitude
      towards disease and medication, dose adjustments, reasons for discontinuation and
      plasma concentration of erlotinib will be explored. METHODS/DESIGN: In this
      prospective observational cohort study 65 NSCLC patients of 18 years or older
      starting treatment with erlotinib will be followed for a period up to 16 weeks.
      The main study parameters are adherence, the plasma concentration of erlotinib
      and the number and grade of side-effects. At baseline and on erlotinib treatment
      in weeks 3-4, 8-9, 12 and 15-16, patients will be asked to fill out a
      questionnaire. In weeks 3-4, 8-9 and 15-16 blood samples are collected, which
      will be analysed for plasma concentration of erlotinib. Adherence will be
      measured using a medication event monitoring system. DISCUSSION: The present
      study aims to get more insight into patients' experiences with the use of
      erlotinib in daily practice and the various aspects that govern adherence. We
      hypothesize that side-effects play an important role in the way patients use
      erlotinib. We expect that the present study will provide valuable knowledge which
      will be useful for health care professionals to develop interventions to support
      patients. This approach will improve the adherence and persistence with the use
      of erlotinib in order to derive optimal benefit from the medication. TRIAL
      REGISTRATION: NTR1830.

PMID- 21722355
TI  - Predicting ADL disability in community-dwelling elderly people using physical
      frailty indicators: a systematic review.
AB  - BACKGROUND: Disability in Activities of Daily Living (ADL) is an adverse outcome
      of frailty that places a burden on frail elderly people, care providers and the
      care system. Knowing which physical frailty indicators predict ADL disability is
      useful in identifying elderly people who might benefit from an intervention that
      prevents disability or increases functioning in daily life. The objective of this
      study was to systematically review the literature on the predictive value of
      physical frailty indicators on ADL disability in community-dwelling elderly
      people. METHODS: A systematic search was performed in 3 databases (PubMed,
      CINAHL, EMBASE) from January 1975 until April 2010. Prospective, longitudinal
      studies that assessed the predictive value of individual physical frailty
      indicators on ADL disability in community-dwelling elderly people aged 65 years
      and older were eligible for inclusion. Articles were reviewed by two independent
      reviewers who also assessed the quality of the included studies. RESULTS: After
      initial screening of 3081 titles, 360 abstracts were scrutinized, leaving 64 full
      text articles for final review. Eventually, 28 studies were included in the
      review. The methodological quality of these studies was rated by both reviewers
      on a scale from 0 to 27. All included studies were of high quality with a mean
      quality score of 22.5 (SD 1.6). Findings indicated that individual physical
      frailty indicators, such as weight loss, gait speed, grip strength, physical
      activity, balance, and lower extremity function are predictors of future ADL
      disability in community-dwelling elderly people. CONCLUSIONS: This review shows
      that physical frailty indicators can predict ADL disability in community-dwelling
      elderly people. Slow gait speed and low physical activity/exercise seem to be the
      most powerful predictors followed by weight loss, lower extremity function,
      balance, muscle strength, and other indicators. These findings should be
      interpreted with caution because the data of the different studies could not be
      pooled due to large variations in operationalization of the indicators and ADL
      disability across the included studies. Nevertheless, our study suggests that
      monitoring physical frailty indicators in community-dwelling elderly people might
      be useful to identify elderly people who could benefit from disability prevention
      programs.

PMID- 21722356
TI  - Optimal designs for population pharmacokinetic studies of oral artesunate in
      patients with uncomplicated falciparum malaria.
AB  - BACKGROUND: Currently, population pharmacokinetic (PK) studies of anti-malarial
      drugs are designed primarily by the logistical and ethical constraints of taking
      blood samples from patients, and the statistical models that are fitted to the
      data are not formally considered. This could lead to imprecise estimates of the
      target PK parameters, and/or designs insufficient to estimate all of the
      parameters. Optimal design methodology has been developed to determine blood
      sampling schedules that will yield precise parameter estimates within the
      practical constraints of sampling the study populations. In this work optimal
      design methods were used to determine sampling designs for typical future
      population PK studies of dihydroartemisinin, the principal biologically active
      metabolite of oral artesunate. METHODS: Optimal designs were derived using freely
      available software and were based on appropriate structural PK models from an
      analysis of data or the literature and key sampling constraints identified in a
      questionnaire sent to active malaria researchers (3-4 samples per patient, at
      least 15 minutes between samples). The derived optimal designs were then
      evaluated via simulation-estimation. RESULTS: The derived optimal sampling
      windows were 17 to 29 minutes, 30 to 57 minutes, 2.5 to 3.7 hours and 5.8 to 6.6
      hours for non-pregnant adults; 16 to 29 minutes, 31 minutes to 1 hour, 2.0 to 3.4
      hours and 5.5 to 6.6 hours for designs with non-pregnant adults and children and
      35 to 59 minutes, 1.2 to 3.4 hours, 3.4 to 4.9 hours and 6.0 to 8.0 hours for
      pregnant women. The optimal designs resulted in acceptable precision of the PK
      parameters. CONCLUSIONS: The proposed sampling designs in this paper are robust
      and efficient and should be considered in future PK studies of oral artesunate
      where only three or four blood samples can be collected.

PMID- 21722357
TI  - Mothers' beliefs about infant teething in Enugu, South-east Nigeria: a cross
      sectional study.
AB  - BACKGROUND: Parents and Health Care Workers have traditionally attributed a
      variety of symptoms to teething in young children. Some of these symptoms may
      however connote underlying serious medical condition in a child. There is little
      evidence to support these beliefs despite their implications on management of a
      symptomatic teething child. This study therefore seeks determine the beliefs and
      problems mothers associate with teething in Enugu, South-east Nigeria. FINDINGS:
      A cross-sectional survey involving sixty mothers presenting at a Children's
      clinic in Enugu metropolis using questionnaire. More than 90% of the respondents
      thought that babies can experience medical problems as a result of teething. The
      commonest medical problems perceived to be associated with teething were fever
      (71.7%), loose stools (58.3%) and vomiting (35%). CONCLUSION: Mothers still
      associate a variety of symptoms of childhood illnesses to teething and this
      association is not evidence based and could lead to delayed interventions,
      increased morbidity and mortality of children. It is important therefore that
      mothers and health workers caring for young children are educated on the need to
      seek prompt medical attentions in a symptomatic child.

PMID- 21722358
TI  - Correlation between driving-related skill and alcohol use in young-adults from
      six European countries: the TEN-D by Night Project.
AB  - BACKGROUND: Only few studies with small experimental samples investigated the
      impact of psychoactive substances on driving performance. We conducted a
      multicenter international cross-sectional study to evaluate the correlation
      between alcohol use and driving-related skill as measured by brake reaction time
      (RT). METHODS: Before and after the entrance into randomly selected recreational
      sites from six European countries, all subjects aged 16-35 years, owning a driver
      license, were asked to compile a structured socio-demographic questionnaire and
      measure RT (SimuNomad3 driving simulator), breath alcohol concentration (BAC;
      Drager Alcoltest), and drug use (Oratect III saliva test, only at the exit).
      Mixed regression modeling was used to evaluate the independent association
      between RT and alcohol concentration or drug use. RESULTS: Before the entrance
      into the recreational site, 4534 subjects completed all assessments and composed
      the final sample. Their mean age was 23.1+/-4.2 y; 68.3% were males; 54.7% had
      BAC>0 g/L (assumed alcoholics); 7.5% declared illegal drug assumption (mostly
      cannabis). After the exit, 3019 also completed the second assessment: 71.7%
      showed BAC>0 g/L. Controlling for age, gender, educational level, occupation,
      driver license years, and drug use, BAC was positively associated with RT,
      achieving significance, however, only when BAC was higher than 0.49 g/L.
      Significant interaction terms were found between BAC and female gender or drug
      use, with highest RTs (>1 sec.) recorded among drug users with BAC>or=1 g/L.
      CONCLUSIONS: This field study confirms previous experimental data on the negative
      impact of alcohol use on driving-related skill, supporting regulations and
      educational campaigns aimed at discouraging driving after consumption of
      psychoactive substances.

PMID- 21722359
TI  - Metastatic breast carcinoma in the mandible presenting as a periodontal abscess:
      a case report.
AB  - INTRODUCTION: Tumors can metastasize to the oral cavity and affect the jaws, soft
      tissue and salivary glands. Oral cavity metastases are considered rare and
      represent approximately 1% of all oral malignancies. Because of their rarity and
      atypical clinical and radiographic appearance, metastatic lesions are considered
      a diagnostic challenge. The purpose of this report is to present a rare case of a
      metastatic breast carcinoma mimicking a periodontal abscess in the mandible. CASE
      PRESENTATION: A 55-year-old Caucasian woman was referred to our clinic for
      evaluation of bisphosphonate-induced jaw osteonecrosis. She had undergone
      modified radical mastectomy with axillary lymph node dissection for invasive
      ductal carcinoma of the left breast. Her clinical examination showed diffuse
      swelling and a periodontal pocket of 6 mm exhibiting suppuration in the posterior
      right mandible. Moreover, paresthesia of the lower right lip and chin was noted.
      There were no significant radiographic findings other than alveolar bone loss due
      to her periodontal disease. Although the lesion resembled a periodontal abscess,
      metastatic carcinoma of the breast was suspected on the basis of the patient's
      medical history. The area was biopsied, and histological analysis confirmed the
      final diagnosis of metastatic breast carcinoma. CONCLUSION: The general dentist
      or dental specialist should maintain a high level of suspicion while evaluating
      patients with a history of cancer. Paresthesias of the lower lip and the chin
      should be considered ominous signs of metastatic disease. This case highlights
      the importance of the value of a detailed medical history and thorough clinical
      examination for the early detection of metastatic tumors in the oral cavity.

PMID- 21722360
TI  - Three variations of the laryngeal nerve in the same patient: a case report.
AB  - INTRODUCTION: A non-recurrent course is a rare anatomic variation of the inferior
      laryngeal nerve (ILN). Bilateral extra-laryngeal bifurcation of the ILN seldom
      occurs before its laryngeal entry. Anastomosis between the ILN and cervical
      sympathetic chain is another rare anatomic feature. The prevalence of extra
      laryngeal branching of the non-recurrent nerve is unknown. We present an example
      of triple anatomic variations of ILNs in the same patient, and also two anatomic
      variations in the same nerve. CASE PRESENTATION: A 56-year-old Caucasian man with
      a large toxic multi-nodular goiter was surgically treated with total
      thyroidectomy. Both his right and left ILNs were identified, fully exposed and
      preserved along their cervical courses. We discovered many variations during
      bilateral exploration of the two ILNs. His right ILN was non-recurrent. This non
      recurrent ILN showed a terminal division before laryngeal entry. The left nerve
      had a usual course as a recurrent laryngeal nerve (RLN) at his tracheaesophageal
      groove. We also discovered bifurcation of his RLN beginning at a neurovascular
      (RLN and inferior thyroid artery) crossing point. Anterior and posterior branches
      of both nerves entered his larynx separately. The sympathetic inferior laryngeal
      anastomotic branch (SILAB) between the posterior branch of his left ILN and the
      cervical sympathetic chain was established in the distal part of the nerve before
      laryngeal entry. CONCLUSION: A non-recurrent nerve and extra-laryngeal branching
      of the ILN are two different variations. The coincidence of a right non-recurrent
      ILN and bilateral bifurcation of both nerves is a very interesting feature. SILAB
      is a rare additional finding as a third anatomic variation in the same patient.
      Extra-laryngeal terminal division of a non-recurrent ILN is an extremely unusual
      anatomic finding. Two anatomic variations have occurred in the same nerve, like
      "the variation of the variation".

PMID- 21722361
TI  - Reproductive health for refugees by refugees in Guinea IV: Peer education and HIV
      knowledge, attitudes, and reported practices.
AB  - BACKGROUND: Both conflict and HIV affect sub-Saharan Africa, and supportive
      approaches for HIV prevention among refugees are crucial. Peer education has been
      associated with improved HIV outcomes, though relatively little research has been
      published on refugee settings. The primary objective of this study was to assess
      whether exposure to refugee peer education was associated with improved HIV
      knowledge, attitudes, or practice outcomes among refugees in Guinea. Secondary
      objectives were to assess whether gender, age, or formal education were more
      strongly associated than peer education with improved HIV outcomes. METHODS: Data
      was collected by cross-sectional survey from 889 reproductive-age men and women
      in 23 camps in the Forest Region of Guinea. Selected exposures (i.e. peer
      education, gender, formal education, age) were analysed for associations with HIV
      outcomes using logistic regression odds ratios (OR). RESULTS: Most participants
      (88%) had heard of HIV, particularly those exposed to peer or formal education.
      Most correctly identified ways to protect themselves, while maintaining
      misconceptions about HIV transmission. Women and those exposed to either peer or
      formal education had significantly fewer misconceptions. Half of participants
      considered themselves at risk of HIV, women with 52% higher odds than men
      (adjusted OR 1.52, 95%CI 1.01-2.29). Participants exposed to peer education had
      more than twice the odds of reporting having made HIV-avoidant behavioural
      changes than unexposed participants (72% versus 58%; adjusted OR 2.49, 95%CI 1.52
      4.08). While women had 57% lower odds than men of reporting HIV-avoidant
      behavioural changes (OR 0.43, 95%CI 0.31-0.60), women exposed to peer education
      had greater odds than exposed men of reporting HIV-avoidant changes (OR 2.70
      versus OR 1.95). Staying faithful (66%) was the most frequent behavioural change
      reported. CONCLUSIONS: Peer education was most strongly associated with reported
      HIV-avoidant behaviour change. Gender was most associated with HIV knowledge and
      risk perception. Refugee women had fewer misconceptions than men had, but were
      more likely to report HIV risk and less likely to report making behavioural
      changes. Peer education appears promising for HIV interventions in chronic
      emergency settings, if gender disparities and related barriers to condom usage
      are also addressed.

PMID- 21722362
TI  - The impact of diabetes on tuberculosis treatment outcomes: a systematic review.
AB  - BACKGROUND: Multiple studies of tuberculosis treatment have indicated that
      patients with diabetes mellitus may experience poor outcomes.We performed a
      systematic review and meta-analysis to quantitatively summarize evidence for the
      impact of diabetes on tuberculosis outcomes. METHODS: We searched PubMed, EMBASE
      and the World Health Organization Regional Indexes from 1 January 1980 to 31
      December 2010 and references of relevant articles for reports of observational
      studies that included people with diabetes treated for tuberculosis. We reviewed
      the full text of 742 papers and included 33 studies of which 9 reported culture
      conversion at two to three months, 12 reported the combined outcome of failure
      and death, 23 reported death, 4 reported death adjusted for age and other
      potential confounding factors, 5 reported relapse, and 4 reported drug resistant
      recurrent tuberculosis. RESULTS: Diabetes is associated with an increased risk of
      failure and death during tuberculosis treatment. Patients with diabetes have a
      risk ratio (RR) for the combined outcome of failure and death of 1.69 (95% CI,
      1.36 to 2.12). The RR of death during tuberculosis treatment among the 23
      unadjusted studies is 1.89 (95% CI, 1.52 to 2.36), and this increased to an
      effect estimate of 4.95 (95% CI, 2.69 to 9.10) among the 4 studies that adjusted
      for age and other potential confounding factors. Diabetes is also associated with
      an increased risk of relapse (RR, 3.89; 95% CI, 2.43 to 6.23). We did not find
      evidence for an increased risk of tuberculosis recurrence with drug resistant
      strains among people with diabetes. The studies assessing sputum culture
      conversion after two to three months of tuberculosis therapy were heterogeneous
      with relative risks that ranged from 0.79 to 3.25. CONCLUSIONS: Diabetes
      increases the risk of failure and death combined, death, and relapse among
      patients with tuberculosis. This study highlights a need for increased attention
      to treatment of tuberculosis in people with diabetes, which may include testing
      for suspected diabetes, improved glucose control, and increased clinical and
      therapeutic monitoring.

PMID- 21722363
TI  - Increased B-type natriuretic peptide and decreased proteinuria might reflect
      decreased capillary leakage and is associated with a better outcome in patients
      with severe burns.
AB  - INTRODUCTION: It is difficult to adjust fluid balance adequately in patients with
      severe burns due to various physical changes. B-type natriuretic peptide (BNP) is
      emerging as a potential marker of hydration state. Proteinuria is used as a
      predictor of outcome in severe illness and might correlate to systemic capillary
      leakage. This study investigates whether combining BNP and proteinuria can be
      used as a guide for individualized resuscitation and as a predictor of outcome in
      patients with severe burns. METHODS: From 2006 to 2009, 38 consecutive patients
      (age 47 +/- 15 years, 74% male) with severe burns were included and followed for
      20 days. All had normal kidney function at admission. BNP and proteinuria were
      routinely measured. Ordered and actually administered fluid resuscitation volumes
      were recorded. The Sequential Organ Failure Assessment (SOFA) score was used as
      the measure of outcome. RESULTS: BNP increased during follow-up, reaching a
      plateau level at Day 3. Based on median BNP levels at Day 3, patients were
      divided into those with low BNP and those with high BNP levels. Both groups had
      comparable initial SOFA scores. Patients with high BNP received less fluid from
      Days 3 to 10. Furthermore, patients with a high BNP at Day 3 had less morbidity,
      reflected by lower SOFA scores on the following days. To minimize effects of
      biological variability, proteinuria on Days 1 and 2 was averaged. By dividing the
      patients based on median BNP at Day 3 and median proteinuria, patients with high
      BNP and low proteinuria had significantly lower SOFA scores during the entire
      follow-up period compared to those patients with low BNP and high proteinuria.
      CONCLUSIONS: Patients with higher BNP levels received less fluid. This might be
      explained by a lower capillary leakage in these patients, resulting in more
      intravascular fluid and consequently an increase in BNP. In combination with low
      proteinuria, possibly reflecting minimal systemic capillary leakage, a high BNP
      level was associated with a better outcome. BNP and proteinuria have prognostic
      potential in severely burned patients and may be used to adjust individual
      resuscitation.

PMID- 21722364
TI  - Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial
      lung disease: reversal by caveolin-1 scaffolding domain peptide.
AB  - Interstitial lung disease (ILD) is a major cause of morbidity and mortality in
      scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell
      population implicated in the pathogenesis of fibrosing disorders. Given the
      recently recognized importance of caveolin-1 in regulating function and signaling
      in SSc monocytes, in the present study we examined the role of caveolin-1 in the
      migration and/or trafficking and phenotype of monocytes and fibrocytes in
      fibrotic lung disease in human patients and an animal model. These studies fill a
      gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD
      pathology. We found that C-X-C chemokine receptor type 4-positive
      (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are
      present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most
      prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1
      (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes,
      which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold
      increased migration toward CXCL12 compared to control monocytes. Restoration of
      caveolin-1 function by administering the caveolin scaffolding domain (CSD)
      peptide reverses this hypermigration. Similarly, transforming growth factor beta
      treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold
      increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit
      a different phenotype than normal monocytes, expressing high levels of ColI, CD14
      and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for
      such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not
      in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that
      CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest
      that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell
      migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD
      may result from the altered phenotype and migratory activity of their monocyte
      precursors.

PMID- 21722365
TI  - Developmental evolution of flowering plant pollen tube cell walls: callose
      synthase (CalS) gene expression patterns.
AB  - BACKGROUND: A number of innovations underlie the origin of rapid reproductive
      cycles in angiosperms. A critical early step involved the modification of an
      ancestrally short and slow-growing pollen tube for faster and longer distance
      transport of sperm to egg. Associated with this shift are the predominantly
      callose (1,3-beta-glucan) walls and septae (callose plugs) of angiosperm pollen
      tubes. Callose synthesis is mediated by callose synthase (CalS). Of 12 CalS gene
      family members in Arabidopsis, only one (CalS5) has been directly linked to
      pollen tube callose. CalS5 orthologues are present in several monocot and eudicot
      genomes, but little is known about the evolutionary origin of CalS5 or what its
      ancestral function may have been. RESULTS: We investigated expression of CalS in
      pollen and pollen tubes of selected non-flowering seed plants (gymnosperms) and
      angiosperms within lineages that diverged below the monocot/eudicot node. First,
      we determined the nearly full length coding sequence of a CalS5 orthologue from
      Cabomba caroliniana (CcCalS5) (Nymphaeales). Semi-quantitative RT-PCR
      demonstrated low CcCalS5 expression within several vegetative tissues, but strong
      expression in mature pollen. CalS transcripts were detected in pollen tubes of
      several species within Nymphaeales and Austrobaileyales, and comparative analyses
      with a phylogenetically diverse group of sequenced genomes indicated homology to
      CalS5. We also report in silico evidence of a putative CalS5 orthologue from
      Amborella. Among gymnosperms, CalS5 transcripts were recovered from germinating
      pollen of Gnetum and Ginkgo, but a novel CalS paralog was instead amplified from
      germinating pollen of Pinus taeda. CONCLUSION: The finding that CalS5 is the
      predominant callose synthase in pollen tubes of both early-diverging and model
      system angiosperms is an indicator of the homology of their novel callosic pollen
      tube walls and callose plugs. The data suggest that CalS5 had transient
      expression and pollen-specific functions in early seed plants and was then
      recruited to novel expression patterns and functions within pollen tube walls in
      an ancestor of extant angiosperms.

PMID- 21722366
TI  - A study of neural-related microRNAs in the developing amphioxus.
AB  - BACKGROUND: MicroRNAs are small noncoding RNAs regulating expression of protein
      coding genes at post-transcriptional level and controlling several biological
      processes. At present microRNAs have been identified in various metazoans and
      seem also to be involved in brain development, neuronal differentiation and
      subtypes specification. An approach to better understand the role of microRNAs in
      animal gene expression is to determine temporal and tissue-specific expression
      patterns of microRNAs in different model organisms. Therefore, we have
      investigated the expression of six neural related microRNAs in amphioxus, an
      organism having an important phylogenetic position in terms of understanding the
      origin and evolution of chordates. RESULTS: In amphioxus, all the microRNAs we
      examined are expressed in specific regions of the CNS, and some of them are
      correlated with specific cell types. In addition, miR-7, miR-137 and miR-184 are
      also expressed in endodermal and mesodermal tissues. Several potential targets
      expressed in the nervous system of amphioxus have been identified by
      computational prediction and some of them are coexpressed with one or more
      miRNAs. CONCLUSION: We identified six miRNAs that are expressed in the nervous
      system of amphioxus in a variety of patterns. miR-124 is found in both
      differentiating and mature neurons, miR-9 in differentiated neurons, miR-7, miR
      137 and miR-184 in restricted CNS regions, and miR-183 in cells of sensory
      organs. Therefore, such amphioxus miRNAs may play important roles in regional
      patterning and/or specification of neuronal cell types.

PMID- 21722367
TI  - Using Geographic Information Systems (GIS) to assess the role of the built
      environment in influencing obesity: a glossary.
AB  - Features of the built environment are increasingly being recognised as
      potentially important determinants of obesity. This has come about, in part,
      because of advances in methodological tools such as Geographic Information
      Systems (GIS). GIS has made the procurement of data related to the built
      environment easier and given researchers the flexibility to create a new
      generation of environmental exposure measures such as the travel time to the
      nearest supermarket or calculations of the amount of neighbourhood greenspace.
      Given the rapid advances in the availability of GIS data and the relative ease of
      use of GIS software, a glossary on the use of GIS to assess the built environment
      is timely. As a case study, we draw on aspects the food and physical activity
      environments as they might apply to obesity, to define key GIS terms related to
      data collection, concepts, and the measurement of environmental features.

PMID- 21722368
TI  - An unusual case of congenital melanocytic nevus presenting as neurocutaneous
      melanoma coexisting with Tuberous Sclerosis complex: A case report.
AB  - INTRODUCTION: Congenital melanocytic nevi are among the several known risk
      factors for the development of melanoma. Neurocutaneous melanosis is a rare,
      congenital, non-hereditary disorder characterized by the presence of multiple
      and/or giant congenital melanocytic nevi. It is a rare condition, with fewer than
      200 cases reported in the literature. Its association with tuberous sclerosis
      complex, a form of the neurocutaneous syndrome, is an unusual finding which, to
      the best of our knowledge, has not been documented in the English literature so
      far. Herein we present the first case documenting such an association in a 16
      year-old post-pubertal Indian girl. CASE PRESENTATION: In this report, we
      describe the case of a 16-year-old Indian girl who presented to our hospital with
      swelling on the scalp which had progressed from the hairline to just above the
      left brow, causing mechanical ptosis. She was born with a black-pigmented
      triangular patch covered with hair over the scalp which had increased in size
      over a period of eight years after birth. An X-ray of her skull and
      ultrasonography revealed soft tissue swelling in the left temporofrontoparietal
      region. Magnetic resonance imaging of her brain showed the presence of 8.99 cm *
      2.26 cm abnormal signal intensity involving the scalp, a few small tubers with
      cortical dysplasia in the left frontoparietal region with asymmetric dilatation,
      and the presence of calcified subependymal nodules within the left lateral
      ventricle. These findings were suggestive of tuberous sclerosis. A
      histopathological examination of the swelling was suggestive of congenital
      melanocytic nevi. The patient underwent surgery. Excision of the tumor with
      primary skin grafting was done, with the graft being taken from the medial aspect
      of the right thigh. CONCLUSION: This case warrants further research to provide
      concrete evidence of an association of neurocutaneous melanoma with tuberous
      sclerosis complex. Research should be conducted to prove whether this is an
      unusual association or a new syndrome. Also, similar cases in other parts of the
      globe should be documented, as they would provide substantial support for such an
      association.

PMID- 21722369
TI  - Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different
      cell types in the rat spinal cord.
AB  - BACKGROUND: Previous studies have demonstrates that, after nerve injury,
      extracellular signal-regulated protein kinase (ERK) activation in the spinal cord
      initially in neurons, then microglia, and finally astrocytes. In addition,
      phosphorylation of ERK (p-ERK) contributes to nociceptive responses following
      inflammation and/or nerve injury. However, the role of spinal cells and the
      ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood.
      The present study analyzed activation of spinal cells and the ERK/MAPK pathway in
      a rat model of bone cancer pain. RESULTS: A Sprague Dawley rat model of bone
      cancer pain was established and the model was evaluated by a series of tests.
      Moreover, fluorocitrate (reversible glial metabolic inhibitor) and U0126 (a MEK
      inhibitor) was administered intrathecally. Western blots and double
      immunofluorescence were used to detect the expression and location of
      phosphorylation of ERK (p-ERK). Our studies on pain behavior show that the time
      between day 6 and day 18 is a reasonable period ("time window" as the remaining
      stages) to investigate bone cancer pain mechanisms and to research analgesic
      drugs. Double-labeling immunofluorescence revealed that p-ERK was sequentially
      expressed in neurons, microglia, and astrocytes in the L4-5 superficial spinal
      cord following inoculation of Walker 256 cells. Phosphorylation of ERK (p-ERK)
      and the transcription factor cAMP response element-binding protein (p-CREB)
      increased in the spinal cord of CIBP rats, which was attenuated by intrathecal
      injection of fluorocitrate or U0126. CONCLUSIONS: The ERK inhibitors could have a
      useful role in CIBP management, because the same target is expressed in various
      cells at different times.

PMID- 21722370
TI  - Survival advantages conferred to colon cancer cells by E-selectin-induced
      activation of the PI3K-NFkappaB survival axis downstream of Death receptor-3.
AB  - BACKGROUND: Extravasation of circulating cancer cells is a key event of
      metastatic dissemination that is initiated by the adhesion of cancer cells to
      endothelial cells. It requires interactions between adhesion receptors on
      endothelial cells and their counter-receptors on cancer cells. Notably, E
      selectin, a major endothelial adhesion receptor, interacts with Death receptor-3
      present on metastatic colon carcinoma cells. This interaction confers metastatic
      properties to colon cancer cells by promoting the adhesion of cancer cells to
      endothelial cells and triggering the activation of the pro-migratory p38 and pro
      survival ERK pathways in the cancer cells. In the present study, we investigated
      further the mechanisms by which the E-selectin-activated pathways downstream of
      DR3 confer a survival advantage to colon cancer cells. METHODS: Cell survival has
      been ascertained by using the WST-1 assay and by evaluating the activation of the
      PI3 kinase/NFkappaB survival axis. Apoptosis has been assayed by determining DNA
      fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3.
      DR3 isoforms have been identified by PCR. For more precise quantification,
      targeted PCR reactions were carried out, and the amplified products were analyzed
      by automated chip-based microcapillary electrophoresis on an Agilent 2100
      Bioanalyzer instrument. RESULTS: Interaction between DR3-expressing HT29 colon
      carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway.
      Moreover, p65/RelA, the anti-apoptotic subunit of NFkappaB, is rapidly
      translocated to the nucleus in response to E-selectin. This translocation is
      impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt
      pathway increases the cleavage of caspase 8 in colon cancer cells treated with E
      selectin and this effect is still further increased when both ERK and PI3K
      pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell
      lines such as HT29 and SW620 express higher levels of a splice variant of DR3
      that has no trans-membrane domain and no death domain. CONCLUSION: Colon cancer
      cells acquire an increased capacity to survive via the activation of the
      PI3K/NFkappaB pathway following the stimulation of DR3 by E-selectin. Generation
      of a DR3 splice variant devoid of death domain can further contribute to protect
      against apoptosis.

PMID- 21722371
TI  - Gabapentin for complex regional pain syndrome in Machado-Joseph disease: a case
      report.
AB  - INTRODUCTION: Chronic pain is a common problem for patients with Machado-Joseph
      disease. Most of the chronic pain in Machado-Joseph disease has been reported to
      be of musculoskeletal origin, but now there seems to be different chronic pain in
      patients with Machado-Joseph disease. CASE PRESENTATION: A 29-year-old man (Han
      Chinese, Hoklo) with Machado-Joseph disease experienced severe chronic pain in
      both feet, cutaneous thermal change, thermal hypersensitivity, focal edema, and
      sweating and had a history of bone fracture. These symptoms were compatible with
      a diagnosis of complex regional pain syndrome. After common analgesics failed to
      relieve his pain, gabapentin was added and titrated to 2000 mg/day (500 mg every
      six hours) in less than two weeks. This relieved 40% of his pain and led to
      significant clinical improvement. CONCLUSIONS: The pathophysiology of complex
      regional pain syndrome includes peripheral and central sensitizations, the latter
      of which might be associated with the neurodegeneration in Machado-Joseph
      disease. In this report, we suggest that gabapentin could inhibit central
      sensitization as an adjunct for complex regional pain syndrome in patients with
      Machado-Joseph disease.

PMID- 21722372
TI  - Understanding multinational companies in public health systems, using a
      competitive advantage framework.
AB  - BACKGROUND: This paper discusses the findings of a study which developed five
      case studies of five multinational health care companies involved in public
      health care systems. Strategies were analysed in terms of attitude to marketing,
      pricing and regulation. The company strategies have been subjected to an analysis
      using Porter's Five Forces, a business strategy framework, which is unusual in
      health policy studies. METHODS: This paper shows how analysing company strategy
      using a business tool can contribute to understanding the strategies of global
      capital in national health systems. It shows how social science methodologies can
      draw from business methods to explain company strategies. RESULTS: The five
      companies considered in this paper demonstrate that their strategies have many
      dimensions, which fit into Porter's Five Forces of comparative advantage. More
      importantly the Five Forces can be used to identify factors that influence
      company entry into public health care systems. CONCLUSIONS: The process of
      examining the strategic objectives of five health care companies shows that a
      business tool can help to explain the actions and motives of health care
      companies towards public health care systems, and so contribute to a better
      understanding of the strategies of global capital in national health systems.
      Health service commissioners need to understand this dynamic process, which will
      evolve as the nature of public health care systems change.

PMID- 21722373
TI  - Diagnosing delirium in elderly Thai patients: utilization of the CAM algorithm.
AB  - BACKGROUND: Delirium is a common illness among elderly hospitalized patients.
      However, under-recognition of the condition by non-psychiatrically trained
      personnel is prevalent. This study investigated the performance of family
      physicians when detecting delirum in elderly hospitalized Thai patients using the
      Thai version of the Confusion Assessment Method (CAM) algorithm. METHODS: A Thai
      version of the CAM algorithm was developed, and three experienced Thai family
      physicians were trained in its use. The diagnosis of delirium was also carried
      out by four fully qualified psychiatrists using DSM-IV TR criteria, which can be
      considered the gold standard. Sixty-six elderly patients were assessed with MMSE
      Thai 2002, in order to evaluate whether they had dementia upon admission. Within
      three days of admission, each patient was interviewed separately by a
      psychiatrist using DSM-IV TR, and a family physician using the Thai version of
      the CAM algorithm, with both sets of interviewers diagnosing for delirium.
      RESULTS: The CAM algorithm tool, as used by family physicians, demonstrated a
      sensitivity of 91.9% and a specificity of 100.0%, with a PPV of 100.0% and an NPV
      of 90.6%. Interrater agreement between the family physicians and the
      psychiatrists was good (Cohen's Kappa = 0.91, p < 0.0001). The mean of the time
      the family physicians spent using CAM algorithm was significantly briefer than
      that of the psychiatrists using DSM-IV TR. CONCLUSIONS: Family physicians
      performed well when diagnosing delirium in elderly hospitalized Thai patients
      using the Thai version of the CAM algorithm, showing that this measurement tool
      is suitable for use by non-psychiatrically trained personnel, being short, quick,
      and easy to administer. However, proper training on use of the algorithm is
      required.

PMID- 21722374
TI  - A selective sweep of >8 Mb on chromosome 26 in the Boxer genome.
AB  - BACKGROUND: Modern dog breeds display traits that are either breed-specific or
      shared by a few breeds as a result of genetic bottlenecks during the breed
      creation process and artificial selection for breed standards. Selective sweeps
      in the genome result from strong selection and can be detected as a reduction or
      elimination of polymorphism in a given region of the genome. RESULTS: Extended
      regions of homozygosity, indicative of selective sweeps, were identified in a
      genome-wide scan dataset of 25 Boxers from the United Kingdom genotyped at
      ~20,000 single-nucleotide polymorphisms (SNPs). These regions were further
      examined in a second dataset of Boxers collected from a different geographical
      location and genotyped using higher density SNP arrays (~170,000 SNPs). A
      selective sweep previously associated with canine brachycephaly was detected on
      chromosome 1. A novel selective sweep of over 8 Mb was observed on chromosome 26
      in Boxer and for a shorter region in English and French bulldogs. It was absent
      in 171 samples from eight other dog breeds and 7 Iberian wolf samples. A region
      of extended increased heterozygosity on chromosome 9 overlapped with a previously
      reported copy number variant (CNV) which was polymorphic in multiple dog breeds.
      CONCLUSION: A selective sweep of more than 8 Mb on chromosome 26 was identified
      in the Boxer genome. This sweep is likely caused by strong artificial selection
      for a trait of interest and could have inadvertently led to undesired health
      implications for this breed. Furthermore, we provide supporting evidence for two
      previously described regions: a selective sweep on chromosome 1 associated with
      canine brachycephaly and a CNV on chromosome 9 polymorphic in multiple dog
      breeds.

PMID- 21722375
TI  - Experimental and theoretical studies of nanofluid thermal conductivity
      enhancement: a review.
AB  - Correction to Kleinstreuer C, Feng Y: Experimental and theoretical studies of
      nanofluid thermal conductivity enhancement: a review. Nanoscale Research Letters
      2011, 6:229.

PMID- 21722376
TI  - EEG spectral coherence data distinguish chronic fatigue syndrome patients from
      healthy controls and depressed patients--a case control study.
AB  - BACKGROUND: Previous studies suggest central nervous system involvement in
      chronic fatigue syndrome (CFS), yet there are no established diagnostic criteria.
      CFS may be difficult to differentiate from clinical depression. The study's
      objective was to determine if spectral coherence, a computational derivative of
      spectral analysis of the electroencephalogram (EEG), could distinguish patients
      with CFS from healthy control subjects and not erroneously classify depressed
      patients as having CFS. METHODS: This is a study, conducted in an academic
      medical center electroencephalography laboratory, of 632 subjects: 390 healthy
      normal controls, 70 patients with carefully defined CFS, 24 with major
      depression, and 148 with general fatigue. Aside from fatigue, all patients were
      medically healthy by history and examination. EEGs were obtained and spectral
      coherences calculated after extensive artifact removal. Principal Components
      Analysis identified coherence factors and corresponding factor loading patterns.
      Discriminant analysis determined whether spectral coherence factors could
      reliably discriminate CFS patients from healthy control subjects without
      misclassifying depression as CFS. RESULTS: Analysis of EEG coherence data from a
      large sample (n = 632) of patients and healthy controls identified 40 factors
      explaining 55.6% total variance. Factors showed highly significant group
      differentiation (p < .0004) identifying 89.5% of unmedicated female CFS patients
      and 92.4% of healthy female controls. Recursive jackknifing showed predictions
      were stable. A conservative 10-factor discriminant function model was
      subsequently applied, and also showed highly significant group discrimination (p
      < .001), accurately classifying 88.9% unmedicated males with CFS, and 82.4%
      unmedicated male healthy controls. No patient with depression was classified as
      having CFS. The model was less accurate (73.9%) in identifying CFS patients
      taking psychoactive medications. Factors involving the temporal lobes were of
      primary importance. CONCLUSIONS: EEG spectral coherence analysis identified
      unmedicated patients with CFS and healthy control subjects without misclassifying
      depressed patients as CFS, providing evidence that CFS patients demonstrate brain
      physiology that is not observed in healthy normals or patients with major
      depression. Studies of new CFS patients and comparison groups are required to
      determine the possible clinical utility of this test. The results concur with
      other studies finding neurological abnormalities in CFS, and implicate temporal
      lobe involvement in CFS pathophysiology.

PMID- 21722377
TI  - Simple isatin derivatives as free radical scavengers: Synthesis, biological
      evaluation and structure-activity relationship.
AB  - To develop more potent small molecules with enhanced free radical scavenger
      properties, a series of N-substituted isatin derivatives was synthesized, and the
      cytoprotective effect on the apoptosis of PC12 cells induced by H2O2 was
      screened. All these compounds were found to be active, and N-ethyl isatin was
      found with the most potent activity of 69.7% protective effect on PC12 cells.
      Structure-activity relationship analyses showed the bioactivity of N-alkyl
      isatins decline as the increasing of the chain of the alkyl group, furthermore
      odd-even effect was found in the activity, which is interesting for further
      investigation.

PMID- 21722378
TI  - T4 RNA ligase 2 truncated active site mutants: improved tools for RNA analysis.
AB  - BACKGROUND: T4 RNA ligases 1 and 2 are useful tools for RNA analysis. Their use
      upstream of RNA analyses such as high-throughput RNA sequencing and microarrays
      has recently increased their importance. The truncated form of T4 RNA ligase 2,
      comprising amino acids 1-249 (T4 Rnl2tr), is an attractive tool for attachment of
      adapters or labels to RNA 3'-ends. Compared to T4 RNA ligase 1, T4 Rnl2tr has a
      decreased ability to ligate 5'-PO4 ends in single-stranded RNA ligations, and
      compared to the full-length T4 Rnl2, the T4 Rnl2tr has an increased activity for
      joining 5'-adenylated adapters to RNA 3'-ends. The combination of these
      properties allows adapter attachment to RNA 3'-ends with reduced circularization
      and concatemerization of substrate RNA. RESULTS: With the aim of further reducing
      unwanted side ligation products, we substituted active site residues, known to be
      important for adenylyltransferase steps of the ligation reaction, in the context
      of T4 Rnl2tr. We characterized the variant ligases for the formation of unwanted
      ligation side products and for activity in the strand-joining reaction.
      CONCLUSIONS: Our data demonstrate that lysine 227 is a key residue facilitating
      adenylyl transfer from adenylated ligation donor substrates to the ligase. This
      reversal of the second step of the ligation reaction correlates with the
      formation of unwanted ligation products. Thus, T4 Rn2tr mutants containing the
      K227Q mutation are useful for reducing undesired ligation products. We
      furthermore report optimal conditions for the use of these improved T4 Rnl2tr
      variants.

PMID- 21722379
TI  - Precursor B-cell acute lymphoblastic leukemia presenting as obstructive jaundice:
      a case report.
AB  - INTRODUCTION: Acute leukemias very rarely present with jaundice. Herein we report
      a case of precursor B-cell acute lymphoblastic leukemia that presented with
      jaundice in an adult. CASE PRESENTATION: A 44-year-old Hispanic man presented
      with right upper quadrant abdominal pain and jaundice. His initial blood work
      revealed pancytopenia and hyperbilirubinemia. Direct bilirubin was more than 50%
      of the total. His imaging studies were unremarkable except for hepatomegaly. All
      blood screening tests for various hepatocellular etiologies were normal. A
      diagnosis of precursor B-cell acute lymphoblastic leukemia was made upon liver
      biopsy. It also showed lymphocytic infiltration of the hepatic parenchyma leading
      to bile stasis. The diagnosis was subsequently confirmed upon bone marrow biopsy.
      The patient was treated with a hyperfractionated
      cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen. CONCLUSION: Acute
      lymphoblastic leukemia should be one of the differential diagnoses that should be
      considered when initial work-up for jaundice is inconclusive. Some cases of acute
      lymphoblastic leukemia have been reported in both adults and children to have
      presented with the initial manifestation of jaundice, but only a few had no
      radiographic evidence of biliary obstruction. Such presentation can pose a
      serious diagnostic dilemma for clinicians. This manuscript attempts to highlight
      it. Moreover, we believe that if acute lymphoblastic leukemia presentations
      similar to this case continue to be reported in adults or children, a specific
      immunophenotypic expression and cytogenetic abnormality may be found to be
      associated with hepatic infiltration by leukemia. This may substantially
      contribute to the further understanding of the pathophysiology of this
      hematologic disease.

PMID- 21722381
TI  - Induction of Epstein-Barr virus (EBV) lytic cycle in vitro causes lipid
      peroxidation, protein oxidation and DNA damage in lymphoblastoid B cell lines.
AB  - BACKGROUND: We investigated the oxidative modifications of lipids, proteins and
      DNA, potential molecular targets of oxidative stress, in two lymphoblastoid cell
      lines: B95-8 and Raji, after EBV lytic cycle induction. Conjugated dienes level
      was measured as biomarker of lipid peroxidation. Malondialdehyde adduct and
      protein carbonyl levels, as well as protein thiol levels were measured as
      biomarkers of protein oxidation. DNA fragmentation was evaluated as biomarker of
      DNA oxidation. RESULTS: After 48 h (peak of lytic cycle), a significant increase
      in conjugated dienes level was observed in B95-8 and Raji cell lines (p = 0.0001
      and p = 0.019 respectively). Malondialdehyde adduct, protein carbonyl levels were
      increased in B95-8 and Raji cell lines after EBV lytic cycle induction as
      compared to controls (MDA-adduct: p = 0.008 and p = 0.006 respectively; Carbonyl:
      p = 0.003 and p = 0.0039 respectively). Proteins thiol levels were decreased by
      induction in B95-8 and Raji cell lines (p = 0.046; p = 0.002 respectively). DNA
      fragmentation was also detected in B95-8 and Raji cell lines after EBV lytic
      cycle induction as compared to controls. CONCLUSION: The results of this study
      demonstrate the presence of increased combined oxidative modifications in lipids,
      proteins in B95-8 and Raji cells lines after EBV lytic cycle induction. These
      results suggest that lipid peroxidation, protein oxidation and DNA fragmentation
      are generally induced during EBV lytic cycle induction and probably contribute to
      the cytopathic effect of EBV.

PMID- 21722382
TI  - Subjective memory complaints, vascular risk factors and psychological distress in
      the middle-aged: a cross-sectional study.
AB  - BACKGROUND: Subjective memory complaints (SMC) are common but their significance
      is still unclear. It has been suggested they are a precursor of mild cognitive
      impairment (MCI) or dementia and an early indicator of cognitive decline.
      Vascular risk factors have an important role in the development of dementia and
      possibly MCI. We therefore aimed to test the hypothesis that vascular risk
      factors were associated with SMC, independent of psychological distress, in a
      middle-aged community-dwelling population. METHODS: A cross-sectional analysis of
      baseline data from the 45 and Up Study was performed. This is a cohort study of
      people living in New South Wales (Australia), and we explored the sample of 45,
      532 participants aged between 45 and 64 years. SMC were defined as 'fair' or
      'poor' on a self-reported five-point Likert scale of memory function. Vascular
      risk factors of obesity, diabetes, hypertension, hypercholesterolemia and smoking
      were identified by self-report. Psychological distress was measured by the
      Kessler Psychological Distress Scale. We tested the model generated from a
      randomly selected exploratory sample (n = 22, 766) with a confirmatory sample of
      equal size. RESULTS: 5, 479/45, 532 (12%) of respondents reported SMC. Using
      multivariate logistic regression, only two vascular risk factors: smoking (OR
      1.18; 95% CI = 1.03 - 1.35) and hypercholesterolaemia (OR 1.19; 95% CI = 1.04 -
      1.36) showed a small independent association with SMC. In contrast psychological
      distress was strongly associated with SMC. Those with the highest levels of
      psychological distress were 7.00 (95% CI = 5.41 - 9.07) times more likely to have
      SMC than the non-distressed. The confirmatory sample also demonstrated the strong
      association of SMC with psychological distress rather than vascular risk factors.
      CONCLUSIONS: In a large sample of middle-aged people without any history of major
      affective illness or stroke, psychological distress was strongly, and vascular
      risk factors only weakly, associated with SMC, although we cannot discount
      psychological distress acting as a mediator in any association between vascular
      risk factors and SMC. Given this, clinicians should be vigilant regarding the
      presence of an affective illness when assessing middle-aged patients presenting
      with memory problems.

PMID- 21722380
TI  - The role of unintegrated DNA in HIV infection.
AB  - Integration of the reverse transcribed viral genome into host chromatin is the
      hallmark of retroviral replication. Yet, during natural HIV infection, various
      unintegrated viral DNA forms exist in abundance. Though linear viral cDNA is the
      precursor to an integrated provirus, increasing evidence suggests that
      transcription and translation of unintegrated DNAs prior to integration may aid
      productive infection through the expression of early viral genes. Additionally,
      unintegrated DNA has the capacity to result in preintegration latency, or to be
      rescued and yield productive infection and so unintegrated DNA, in some
      circumstances, may be considered to be a viral reservoir. Recently, there has
      been interest in further defining the role and function of unintegrated viral
      DNAs, in part because the use of anti-HIV integrase inhibitors leads to an
      abundance of unintegrated DNA, but also because of the potential use of non
      integrating lentiviral vectors in gene therapy and vaccines. There is now
      increased understanding that unintegrated viral DNA can either arise from, or be
      degraded through, interactions with host DNA repair enzymes that may represent a
      form of host antiviral defence. This review focuses on the role of unintegrated
      DNA in HIV infection and additionally considers the potential implications for
      antiviral therapy.

PMID- 21722384
TI  - Association between asymptomatic hyperuricemia and new-onset chronic kidney
      disease in Japanese male workers: a long-term retrospective cohort study.
AB  - BACKGROUND: Hyperuricemia is prevalent in patients with chronic kidney disease
      (CKD). We explored the hypothesis that asymptomatic hyperuricemia may be
      associated with new-onset CKD. METHODS: The participants were all male factory
      workers in Kanagawa, Japan (n = 1,285). All were over 40 years of age and had
      undergone annual health examinations from 1990 to 2007. Individuals with a
      history of gouty attacks were excluded from the study. A retrospective cohort
      study was conducted by following the estimated glomerular filtration rate (eGFR)
      for each participant over a maximum period of 18 years. The endpoint was new
      onset CKD defined as eGFR < 60 mL/min/1.73 m2. The associations between new-onset
      CKD and the presence of hyperuricemia, low serum high-density lipoprotein
      cholesterol, hypertension, diabetes, and obesity were analyzed. RESULTS: The mean
      (+/- standard deviation) follow-up period was 95.2 (+/- 66.7) months, and new
      onset CKD was observed in 100 participants (7.8%) during this follow-up. Cox
      proportional hazards model revealed that the hazard ratio of new-onset CKD due to
      hyperuricemia, low serum high-density lipoprotein cholesterol, hypertension and
      obesity were 3.99 (95% confidence interval: 2.59-6.15), 1.69 (1.00-2.86), 2.00
      (1.29-3.11) and 1.35 (0.87-2.10), respectively. Concerning hyperuricemia, low
      serum high-density lipoprotein cholesterol, hypertension and obesity, the log
      rank tests showed P values of < 0.01, 0.01, < 0.01 and < 0.01, respectively.
      CONCLUSION: The results of this study suggest that asymptomatic hyperuricemia is
      a predictive factor for new-onset CKD for Japanese male workers.

PMID- 21722383
TI  - Phylogeography of the reef fish Cephalopholis argus (Epinephelidae) indicates
      Pleistocene isolation across the Indo-Pacific Barrier with contemporary overlap
      in The Coral Triangle.
AB  - BACKGROUND: The Coral Triangle (CT), bounded by the Philippines, the Malay
      Peninsula, and New Guinea, is the epicenter of marine biodiversity. Hypotheses
      that explain the source of this rich biodiversity include 1) the center of
      origin, 2) the center of accumulation, and 3) the region of overlap. Here we
      contribute to the debate with a phylogeographic survey of a widely distributed
      reef fish, the Peacock Grouper (Cephalopholis argus; Epinephelidae) at 21
      locations (N = 550) using DNA sequence data from mtDNA cytochrome b and two
      nuclear introns (gonadotropin-releasing hormone and S7 ribosomal protein).
      RESULTS: Population structure was significant (PhiST = 0.297, P < 0.001; FST =
      0.078, P < 0.001; FST = 0.099, P < 0.001 for the three loci, respectively) among
      five regions: French Polynesia, the central-west Pacific (Line Islands to
      northeastern Australia), Indo-Pacific boundary (Bali and Rowley Shoals), eastern
      Indian Ocean (Cocos/Keeling and Christmas Island), and western Indian Ocean
      (Diego Garcia, Oman, and Seychelles). A strong signal of isolation by distance
      was detected in both mtDNA (r = 0.749, P = 0.001) and the combined nuclear loci
      (r = 0.715, P < 0.001). We detected evidence of population expansion with
      migration toward the CT. Two clusters of haplotypes were detected in the mtDNA
      data (d = 0.008), corresponding to the Pacific and Indian Oceans, with a low
      level of introgression observed outside a mixing zone at the Pacific-Indian
      boundary. CONCLUSIONS: We conclude that the Indo-Pacific Barrier, operating
      during low sea level associated with glaciation, defines the primary
      phylogeographic pattern in this species. These data support a scenario of
      isolation on the scale of 105 year glacial cycles, followed by population
      expansion toward the CT, and overlap of divergent lineages at the Pacific-Indian
      boundary. This pattern of isolation, divergence, and subsequent overlap likely
      contributes to species richness at the adjacent CT and is consistent with the
      region of overlap hypothesis.

PMID- 21722385
TI  - A rare case of xanthogranuloma of the stomach masquerading as an advanced stage
      tumor.
AB  - BACKGROUND: Xanthogranuloma of the stomach is an extremely rare disease, and this
      lesion has only been found to coexist with early gastric cancer in 2 cases in the
      literature. CASE PRESENTATION: We report a case of xanthogranuloma of the stomach
      combined with early gastric cancer that mimicked an advanced stage tumor. A 65
      year-old female was referred to our hospital because of epigastralgia. During a
      physical examination, a defined abdominal mass was palpable in the region of the
      left hypochondrium. Imaging studies revealed an advanced gastric cancer, which
      was suspected of having infiltrated the abdominal wall. Total gastrectomy and
      resection of the regional lymph node and abdominal wall were performed.
      Histopathologic examination of the resected specimen demonstrated xanthogranuloma
      combined with early gastric cancer. CONCLUSION: Xanthogranuloma presenting as a
      form of SMT (submucosal tumor) of the stomach is an extremely rare disease, and
      diagnosing it preoperatively is difficult. Further accumulation and investigation
      of this entity is necessary.

PMID- 21722386
TI  - A solitary primary subcutaneous hydatid cyst in the abdominal wall of a 70-year
      old woman: a case report.
AB  - INTRODUCTION: A solitary primary hydatid cyst in the subcutaneous abdominal wall
      is an exceptional entity, even in countries where the Echinococcus infestation is
      endemic. CASE PRESENTATION: We report a case of a 70-year-old Caucasian woman who
      presented to our hospital with a subcutaneous mass in the para-umbilical area
      with a non-specific clinical presentation. The diagnosis of subcutaneous hydatid
      cyst was suspected on the basis of radiological findings. A complete surgical
      resection of the mass was performed and the patient had an uneventful post
      operative recovery. The histopathology confirmed the suspected diagnosis.
      CONCLUSION: Hydatid cyst should be considered in the differential diagnosis of
      every subcutaneous cystic mass, especially in regions where the disease is
      endemic. The best treatment is the total excision of the cyst with an intact
      wall.

PMID- 21722387
TI  - Primary extra-cranial meningioma in the right submandibular region of an 18-year
      old woman: a case report.
AB  - INTRODUCTION: Extra-cranial meningioma or ectopic meningioma is a rare tumor.
      This tumor has been reported in various anatomic sites in the head and neck,
      mediastinum, skin and soft tissues. We report a rare case of ectopic meningioma
      in the submandibular region detected by using fine-needle aspiration cytology,
      histopathology and immunohistochemistry. This case represents another unusual
      site for extra-cranial meningioma, which prompted us to report it. CASE
      PRESENTATION: An 18-year-old Dravidian woman presented with swelling in the right
      submandibular region. The computed tomographic scan findings were suggestive of a
      neoplastic mass lesion in the right submandibular region. Fine-needle aspiration
      cytology led to the differential diagnosis of a monomorphic adenoma of a salivary
      gland or an ectopic meningioma. The patient underwent excision of the
      submandibular gland and tumor. The histological examination and
      immunohistochemistry studies confirmed that the lesion was an extra-cranial
      meningioma. At her two-year follow-up examination, there was no recurrence of the
      tumor. CONCLUSION: Our experience with this case indicates that, although rare,
      meningioma should be entertained in the differential diagnosis of a mass lesion
      in the head and neck region.

PMID- 21722389
TI  - Giant condyloma acuminatum of the scrotum in a man with AIDS: a case report.
AB  - INTRODUCTION: Giant condyloma acuminatum, also called a Buschke-Lowenstein tumor,
      first described in 1925, is a slow-growing, locally aggressive, destructive tumor
      of the ano-genital region. Scrotal tumors are rare. Reports on giant condyloma
      acuminatum lesions in patients with HIV and AIDS are surprisingly even rarer.
      CASE PRESENTATION: In this report, we present the case of a 42-year-old African
      man with AIDS who was undergoing anti-retroviral therapy. He was found to have a
      giant condyloma acuminatum of the scrotum. Wide surgical excision and scrotal
      reconstruction with a pedicled anterolateral thigh flap was performed,
      significantly improving his quality of life. CONCLUSION: Decision making
      regarding the goals of surgical intervention in the terminally ill is a complex
      process. The options include conservative medical palliation or palliative
      excision versus a curative excision that has the potential for significant
      morbidity. Wide surgical excision with local flap reconstruction significantly
      improved the quality of life of the patient described herein. The challenges
      presented by emerging or unusual presentations of surgical pathology secondary to
      HIV and AIDS in patients who are on anti-retroviral therapy provide an
      opportunity for research and the establishment of guidelines for the use of
      adjuvant chemotherapy in these patients.

PMID- 21722388
TI  - Construction of a computable cell proliferation network focused on non-diseased
      lung cells.
AB  - BACKGROUND: Critical to advancing the systems-level evaluation of complex
      biological processes is the development of comprehensive networks and
      computational methods to apply to the analysis of systems biology data
      (transcriptomics, proteomics/phosphoproteomics, metabolomics, etc.). Ideally,
      these networks will be specifically designed to capture the normal, non-diseased
      biology of the tissue or cell types under investigation, and can be used with
      experimentally generated systems biology data to assess the biological impact of
      perturbations like xenobiotics and other cellular stresses. Lung cell
      proliferation is a key biological process to capture in such a network model,
      given the pivotal role that proliferation plays in lung diseases including
      cancer, chronic obstructive pulmonary disease (COPD), and fibrosis.
      Unfortunately, no such network has been available prior to this work. RESULTS: To
      further a systems-level assessment of the biological impact of perturbations on
      non-diseased mammalian lung cells, we constructed a lung-focused network for cell
      proliferation. The network encompasses diverse biological areas that lead to the
      regulation of normal lung cell proliferation (Cell Cycle, Growth Factors, Cell
      Interaction, Intra- and Extracellular Signaling, and Epigenetics), and contains a
      total of 848 nodes (biological entities) and 1597 edges (relationships between
      biological entities). The network was verified using four published gene
      expression profiling data sets associated with measured cell proliferation
      endpoints in lung and lung-related cell types. Predicted changes in the activity
      of core machinery involved in cell cycle regulation (RB1, CDKN1A, and MYC/MYCN)
      are statistically supported across multiple data sets, underscoring the general
      applicability of this approach for a network-wide biological impact assessment
      using systems biology data. CONCLUSIONS: To the best of our knowledge, this lung
      focused Cell Proliferation Network provides the most comprehensive connectivity
      map in existence of the molecular mechanisms regulating cell proliferation in the
      lung. The network is based on fully referenced causal relationships obtained from
      extensive evaluation of the literature. The computable structure of the network
      enables its application to the qualitative and quantitative evaluation of cell
      proliferation using systems biology data sets. The network is available for
      public use.

PMID- 21722390
TI  - Primary melanoma of the adrenal gland: a case report and review of the
      literature.
AB  - BACKGROUND: Primary melanoma of the adrenal gland is exceptionally rare as
      demonstrated by the few cases reported in the medical literature, and it has a
      high fatality rate. We present the case of a patient with two relapses and
      survival to date. CASE REPORT: We describe the case of a 58-year-old Caucasian
      woman who consulted her doctor with symptoms of asthenia, anorexia and weight
      loss. A mass was palpated in her abdomen at the height of the left hypochondrium.
      A computed tomographic scan revealed a retroperitoneal mass measuring 10 cm * 15
      cm originating in the left adrenal gland. A left nephroadrenalectomy and
      splenectomy were performed. Histopathologically, the retroperitoneal mass
      corresponded to a melanoma, and no primary melanoma was found in any other
      location. The patient was treated with interferon-alpha-2b. Three years after her
      diagnosis the patient presented with a retroperitoneal relapse of the mass
      measuring 7.2 cm, which was removed. Five years after the first relapse a new
      retroperitoneal relapse mass was diagnosed, which was also removed. Since then
      the patient has been healthy and free from illness. CONCLUSION: Histological and
      immunohistochemical studies, together with the criteria described by Ainsworth et
      al. and Carstens et al., allowed us to diagnose primary melanoma of the adrenal
      gland.

PMID- 21722391
TI  - A simple and efficient tool for trapping gravid Anopheles at breeding sites.
AB  - BACKGROUND: No effective tool currently exists for trapping ovipositing malaria
      vectors. This creates a gap in our ability to investigate the behavior and
      ecology of gravid Anopheles. FINDINGS: Here we describe a simple trap that
      collects ovipositing Anopheline and Culicine mosquitoes. It consists of an
      acetate sheet coated in glue that floats on the water surface. Ten breeding sites
      were selected in rural Tanzania and 10 sticky traps set in each. These caught a
      total of 74 gravid Anopheles (54 An. arabiensis, 1 An. gambiae s.s. and 16
      unamplified) and 1333 gravid Culicines, in just two trap nights. This simple
      sampling tool provides an opportunity to further our understanding of the
      behavior and ecology of gravid female Anophelines. It strongly implies that at
      least two of the major vectors of malaria in Africa land on the water surface
      during the oviposition process, and demonstrates that Anophelines and Culicines
      often share the same breeding sites. CONCLUSION: This simple and efficient trap
      has clear potential for the study of oviposition site choice and productivity,
      gravid dispersal, and vector control techniques which use oviposition behavior as
      a means of disseminating larvicides.

PMID- 21722393
TI  - Spontaneous iliopsoas muscle hematoma in a patient with von Willebrand disease: a
      case report.
AB  - INTRODUCTION: Iliopsoas hemorrhage is a serious complication of bleeding
      disorders that occurs most commonly in patients with hemophilia and less commonly
      in patients with von Willebrand disease. It causes severe pain, muscle
      dysfunction and occasionally femoral nerve palsy. We describe the case of a
      patient with von Willebrand disease type 3 with a large iliopsoas hematoma who
      was treated with a von Willebrand factor concentrate (Humate-P). CASE
      PRESENTATION: A 20-year-old Iranian man was referred to our emergency ward
      because of the gradual onset of right flank pain. He was known to have been
      diagnosed with von Willebrand disease type 3 at age two years old. Magnetic
      resonance imaging showed a mass in the right iliopsoas muscle. The diagnosis of
      iliopsoas hemorrhage and partial femoral nerve palsy was established, and he
      responded to medical treatment. CONCLUSION: We report a case of von Willebrand
      disease type 3 with spontaneous iliopsoas hematoma associated with femoral nerve
      palsy that was well managed with Humate-P treatment.

PMID- 21722392
TI  - Real time analysis of beta(2)-adrenoceptor-mediated signaling kinetics in human
      primary airway smooth muscle cells reveals both ligand and dose dependent
      differences.
AB  - BACKGROUND: beta2-adrenoceptor agonists elicit bronchodilator responses by
      binding to beta2-adrenoceptors on airway smooth muscle (ASM). In vivo, the time
      between drug administration and clinically relevant bronchodilation varies
      significantly depending on the agonist used. Our aim was to utilise a fluorescent
      cyclic AMP reporter probe to study the temporal profile of beta2-adrenoceptor
      mediated signaling induced by isoproterenol and a range of clinically relevant
      agonists in human primary ASM (hASM) cells by using a modified Epac protein fused
      to CFP and a variant of YFP. METHODS: Cells were imaged in real time using a
      spinning disk confocal system which allowed rapid and direct quantification of
      emission ratio imaging following direct addition of beta2-adrenoceptor agonists
      (isoproterenol, salbutamol, salmeterol, indacaterol and formoterol) into the
      extracellular buffer. For pharmacological comparison a radiolabeling assay for
      whole cell cyclic AMP formation was used. RESULTS: Temporal analysis revealed
      that in hASM cells the beta2-adrenoceptor agonists studied did not vary
      significantly in the onset of initiation. However, once a response was initiated,
      significant differences were observed in the rate of this response with
      indacaterol and isoproterenol inducing a significantly faster response than
      salmeterol. Contrary to expectation, reducing the concentration of isoproterenol
      resulted in a significantly faster initiation of response. CONCLUSIONS: We
      conclude that confocal imaging of the Epac-based probe is a powerful tool to
      explore beta2-adrenoceptor signaling in primary cells. The ability to analyse the
      kinetics of clinically used beta2-adrenoceptor agonists in real time and at a
      single cell level gives an insight into their possible kinetics once they have
      reached ASM cells in vivo.

PMID- 21722394
TI  - Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD
      IgMU(null) mice after polyclonal B cell reconstitution.
AB  - BACKGROUND: Non Obese Diabetic mice lacking B cells (NOD.IgMU(null) mice) do not
      develop diabetes despite their susceptible background. Upon reconstitution of B
      cells using a chimera approach, animals start developing diabetes at 20 weeks of
      age. METHODS: We have used the spectratyping technique to follow the T cell
      receptor (TCR) V beta repertoire of NOD.IgMU(null) mice following B cell
      reconstitution. This technique provides an unbiased approach to understand the
      kinetics of TCR expansion. We have also analyzed the TCR repertoire of
      reconstituted animals receiving cyclophosphamide treatment and following tissue
      transplants to identify common aggressive clonotypes. RESULTS: We found that B
      cell reconstitution of NOD.IgMU(null) mice induces a polyclonal TCR repertoire in
      the pancreas 10 weeks later, gradually diversifying to encompass most BV
      families. Interestingly, these clonotypic BV expansions are mainly confined to
      the pancreas and are absent from pancreatic lymph nodes or spleens.
      Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution
      reorganized the predominant TCR repertoires by removing potential regulatory
      clonotypes (BV1, BV8 and BV11) and increasing the frequency of others (BV4,
      BV5S2, BV9, BV16-20). These same clonotypes are more frequently present in
      neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted
      diabetic NOD.IgMU(null) mice, suggesting their higher invasiveness. Phenotypic
      analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell
      reconstituted animals show a predominance of CD19+ B cells with a B:T lymphocyte
      ratio of 4:1. In contrast, in other lymphoid organs (pancreatic lymph nodes and
      spleens) analyzed by FACS, the B:T ratio was 1:1. Lymphocytes infiltrating the
      pancreas secrete large amounts of IL-6 and are of Th1 phenotype after CD3-CD28
      stimulation in vitro. CONCLUSIONS: Diabetes in NOD.IgMU(null) mice appears to be
      caused by a polyclonal repertoire of T cell accumulation in pancreas without much
      lymphoid organ involvement and is dependent on the help by B cells.

PMID- 21722395
TI  - Inhibition of Rho-associated coiled-coil containing protein kinase enhances the
      activation of epidermal growth factor receptor in pancreatic cancer cells.
AB  - BACKGROUND: Rho-associated coiled-coil containing protein kinase (Rho
      kinase/ROCK) is involved in various cellular functions including cell
      proliferation, and is generally considered to be oncogenic, while some studies
      show that ROCK functions as a negative regulator of cancer progression. As a
      result, the precise role of ROCK remains controversial. We have previously
      reported that Rho-kinase/ROCK negatively regulates epidermal growth factor (EGF)
      induced cell proliferation in SW480 colon cancer cells. In the present study, we
      investigated the role of ROCK in EGF receptor (EGFR) signaling in the pancreatic
      cancer cell lines, Panc1, KP3 and AsPc1. RESULTS: In these cells, Y27632, a
      specific ROCK inhibitor, enhanced EGF-induced BrdU incorporation. The blockade of
      EGF stimulation utilizing anti-EGFR-neutralizing antibodies suppressed Panc1 cell
      proliferation. EGF induced RhoA activity, as well as the phosphorylation of
      cofilin and myosin light chain (MLC), both targets of ROCK signaling, and Y27632
      suppressed both of these processes, indicating that the phosphorylation of
      cofilin and MLC by EGF occurs through ROCK in Panc1 cells. EGF-induced
      phosphorylation of EGFR at tyrosine residues was augmented when the cells were
      pretreated with Y27632 or were subjected to gene silencing using ROCK-siRNA. We
      also obtained similar results using transforming growth factor-alpha. In
      addition, EGF-induced phosphorylation of p44/p42 mitogen-activated protein kinase
      and Akt were also enhanced by Y27632 or ROCK-siRNA. Moreover, an
      immunofluorescence microscope study revealed that pretreatment with Y27632
      delayed EGF-induced internalization of EGFR. Taken together, these data indicate
      that ROCK functions to switch off EGFR signaling by promoting the internalization
      of the EGFR. CONCLUSIONS: While EGF first stimulates the activation of the EGFR
      and subsequently increases cancer cell proliferation, EGF concurrently induces
      the activation of ROCK, which then turns off the activated EGFR pathway via a
      negative feedback system.

PMID- 21722396
TI  - The DUNDRUM Quartet: validation of structured professional judgement instruments
      DUNDRUM-3 assessment of programme completion and DUNDRUM-4 assessment of recovery
      in forensic mental health services.
AB  - BACKGROUND: Moving a forensic mental health patient from one level of therapeutic
      security to a lower level or to the community is influenced by more than risk
      assessment and risk management. We set out to construct and validate structured
      professional judgement instruments for consistency and transparency in decision
      making METHODS: Two instruments were developed, the seven-item DUNDRUM-3
      programme completion instrument and the six item DUNDRUM-4 recovery instrument.
      These were assessed for all 95 forensic patients at Ireland's only forensic
      mental health hospital. RESULTS: The two instruments had good internal
      consistency (Cronbach's alpha 0.911 and 0.887). Scores distinguished those
      allowed no leave or accompanied leave from those with unaccompanied leave (ANOVA
      F = 38.1 and 50.3 respectively, p < 0.001). Scores also distinguished those in
      acute/high security units from those in medium or in low secure/pre-discharge
      units. Each individual item distinguished these levels of need significantly. The
      DUNDRUM-3 and DUNDRUM-4 correlated moderately with measures of dynamic risk and
      with the CANFOR staff rated unmet need (Spearman r = 0.5, p < 0.001).
      CONCLUSIONS: The DUNDRUM-3 programme completion items distinguished significantly
      between levels of therapeutic security while the DUNDRUM-4 recovery items
      consistently distinguished those given unaccompanied leave outside the hospital
      and those in the lowest levels of therapeutic security. This data forms the basis
      for a prospective study of outcomes now underway.

PMID- 21722397
TI  - DUNDRUM-2: Prospective validation of a structured professional judgment
      instrument assessing priority for admission from the waiting list for a forensic
      mental health hospital.
AB  - BACKGROUND: The criteria for deciding who should be admitted first from a waiting
      list to a forensic secure hospital are not necessarily the same as those for
      assessing need. Criteria were drafted qualitatively and tested in a prospective
      'real life' observational study over a 6-month period. METHODS: A researcher
      rated all those presented at the weekly referrals meeting using the DUNDRUM-1
      triage security scale and the DUNDRUM-2 triage urgency scale. The key outcome
      measure was whether or not the individual was admitted. RESULTS: Inter-rater
      reliability and internal consistency for the DUNDRUM-2 were acceptable. The
      DUNDRUM-1 triage security score and the DUNDRUM-2 triage urgency score correlated
      r = 0.663. At the time of admission, after a mean of 23.9 (SD35.9) days on the
      waiting list, those admitted had higher scores on the DUNDRUM-2 triage urgency
      scale than those not admitted, with no significant difference between locations
      (remand or sentenced prisoners, less secure hospitals) at the time of admission.
      Those admitted also had higher DUNDRUM-1 triage security scores. At baseline the
      receiver operating characteristic area under the curve for a combined score was
      the best predictor of admission while at the time of admission the DUNDRUM-2
      triage urgency score had the largest AUC (0.912, 95% CI 0.838 to 0.986).
      CONCLUSIONS: The triage urgency items and scale add predictive power to the
      decision to admit. This is particularly true in maintaining equitability between
      those referred from different locations.

PMID- 21722398
TI  - Effects of two Lactobacillus strains on lipid metabolism and intestinal
      microflora in rats fed a high-cholesterol diet.
AB  - BACKGROUND: The hypocholesterolemic effects of lactic acid bacteria (LAB) have
      now become an area of great interest and controversy for many scientists. In this
      study, we evaluated the effects of Lactobacillus plantarum 9-41-A and
      Lactobacillus fermentum M1-16 on body weight, lipid metabolism and intestinal
      microflora of rats fed a high-cholesterol diet. METHODS: Forty rats were assigned
      to four groups and fed either a normal or a high-cholesterol diet. The LAB
      treated groups received the high-cholesterol diet supplemented with Lactobacillus
      plantarum 9-41-A or Lactobacillus fermentum M1-16. The rats were sacrificed after
      a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum
      and liver cholesterol and lipid levels, and fecal cholesterol and bile acid
      concentrations were measured. Liver lipid deposition and adipocyte size were
      evaluated histologically. RESULTS: Compared with rats fed a high-cholesterol diet
      but without LAB supplementation, serum total cholesterol, low-density lipoprotein
      cholesterol and triglycerides levels were significantly decreased in LAB-treated
      rats (p < 0.05), with no significant change in high-density lipoprotein
      cholesterol levels. Hepatic cholesterol and triglyceride levels and liver lipid
      deposition were significantly decreased in the LAB-treated groups (p < 0.05).
      Accordingly, both fecal cholesterol and bile acids levels were significantly
      increased after LAB administration (p < 0.05). Intestinal Lactobacillus and
      Bifidobacterium colonies were increased while Escherichia coli colonies were
      decreased in the LAB-treated groups. Fecal water content was higher in the LAB
      treated groups. Compared with rats fed a high-cholesterol diet, administration of
      Lactobacillus plantarum 9-41-A resulted in decreases in the body weight gain,
      liver and fat pad weight, and adipocytes size (p < 0.05). CONCLUSIONS: This study
      suggests that LAB supplementation has hypocholesterolemic effects in rats fed a
      high-cholesterol diet. The ability to lower serum cholesterol varies among LAB
      strains. Our strains might be able to improve the intestinal microbial balance
      and potentially improve intestinal transit time. Although the mechanism is
      largely unknown, L. plantarum 9-41-A may play a role in fat metabolism.

PMID- 21722399
TI  - Patient Care Teams in treatment of diabetes and chronic heart failure in primary
      care: an observational networks study.
AB  - BACKGROUND: Patient care teams have an important role in providing medical care
      to patients with chronic disease, but insight into how to improve their
      performance is limited. Two potentially relevant determinants are the presence of
      a central care provider with a coordinating role and an active role of the
      patient in the network of care providers. In this study, we aimed to develop and
      test measures of these factors related to the network of care providers of an
      individual patient. METHODS: We performed an observational study in patients with
      type 2 diabetes or chronic heart failure, who were recruited from three primary
      care practices in The Netherlands. The study focused on medical treatment, advice
      on physical activity, and disease monitoring. We used patient questionnaires and
      chart review to measure connections between the patient and care providers, and a
      written survey among care providers to measure their connections. Data on
      clinical performance were extracted from the medical records. We used network
      analysis to compute degree centrality coefficients for the patient and to
      identify the most central health professional in each network. A range of other
      network characteristics were computed including network centralization, density,
      size, diversity of disciplines, and overlap among activity-specific networks.
      Differences across the two chronic conditions and associations with disease
      monitoring were explored. RESULTS: Approximately 50% of the invited patients
      participated. Participation rates of health professionals were close to 100%. We
      identified 63 networks of 25 patients: 22 for medical treatment, 16 for physical
      exercise advice, and 25 for disease monitoring. General practitioners (GPs) were
      the most central care providers for the three clinical activities in both chronic
      conditions. The GP's degree centrality coefficient varied substantially, and
      higher scores seemed to be associated with receiving more comprehensive disease
      monitoring. The degree centrality coefficient of patients also varied
      substantially but did not seem to be associated with disease monitoring.
      CONCLUSIONS: Our method can be used to measure connections between care providers
      of an individual patient, and to examine the association between specific network
      parameters and healthcare received. Further research is needed to refine the
      measurement method and to test the association of specific network parameters
      with quality and outcomes of healthcare.

PMID- 21722400
TI  - Connectedness of healthcare professionals involved in the treatment of patients
      with Parkinson's disease: a social networks study.
AB  - BACKGROUND: Patients with chronic illness typically receive ambulatory treatment
      from multiple health professionals. Connectedness between these professionals may
      influence their clinical decisions and the coordination of patient care. We aimed
      to describe and analyze connectedness in a regional network of health
      professionals involved in ambulatory treatment of patients with Parkinson's
      disease (PD). METHODS: Observational study with 104 health professionals who had
      joined a newly established network (ParkinsonNet) were asked to complete a pre
      structured form to report on their professional contacts with others in the
      network. Using social networks methods, network measures were calculated for the
      total network and for the networks of individual health professionals. We planned
      to test differences between subgroups of health professionals regarding 12
      network measures, using a random permutation method. RESULTS: Ninety-six health
      professionals (92%) provided data on 101 professionals. The reciprocity of
      reported connections was 0.42 in the network of professional contacts. Measures
      characterizing the individual networks showed a wide variation; e.g., density
      varied between 0 and 100% (mean value 28.4%). Health professionals with >=10 PD
      patients had higher values on 7 out of 12 network measures compare to those with
      < 10 PD patients (size, number of connections, two step reach, indegree
      centrality, outdegree centrality, inreach centrality, betweenness centrality).
      Primary care professionals had lower values on 11 out of 12 network measures (all
      but reach efficiency) compared to professionals who were affiliated with a
      hospital. CONCLUSIONS: Our measure of professional connectedness proved to be
      feasible in a regional disease-specific network of health professionals. Network
      measures describing patterns in the professional contacts showed relevant
      variation across professionals. A higher caseload and an affiliation with a
      hospital were associated with stronger connectedness with other health
      professionals.

PMID- 21722401
TI  - Atlantoaxial subluxation as an early manifestation in an adolescent with
      undifferentiated spondyloarthritis: a case report and review of the literature.
AB  - INTRODUCTION: Atlantoaxial instability has been described as a manifestation of
      ankylosing spondylitis (juvenile and adult onset), reactive arthritis, juvenile
      idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been
      reported as an early manifestation of these disorders. We present this case
      report to increase awareness of the condition in the hope that earlier
      recognition of this disease may prevent further serious injury. CASE
      PRESENTATION: We report the case of a 17-year-old Hispanic adolescent woman who
      was initially diagnosed with undifferentiated spondyloarthritis due to peripheral
      arthritis, enthesitis, a positive human leukocyte antigen B27 result, and
      inflammatory spinal pain lasting two months. Our patient experienced persistent
      and worsening occipitocervical pain and signs of myelopathy three months after
      diagnosis; consequently, we found atlantoaxial instability along with cervical
      spine bone erosion and pannus formation. She was treated surgically with a C1-2
      posterior instrumented fusion and at six weeks post-operatively was started on
      tumor necrosis factor alpha blockade. Her occipitocervical symptoms subsided
      following surgery and initiation of immunomodulation. CONCLUSIONS: Our report
      serves to emphasize to pediatric and adult general practitioners, pediatricians,
      internists, family physicians, pediatric and adult rheumatologists and spine
      surgeons that atlantoaxial subluxation may be an early manifestation of
      spondyloarthritis, and that the condition is treatable by surgical intervention
      and immunomodulation.

PMID- 21722402
TI  - Living donor liver transplantation from a donor previously treated with
      interferon for hepatitis C virus: a case report.
AB  - INTRODUCTION: Selecting a marginal donor in liver transplantation (LT) remains
      controversial but is necessary because of the small number of available donors.
      CASE PRESENTATION: A 46-year-old Japanese woman was a candidate to donate her
      liver to her brother, who had decompensated liver cirrhosis of unknown origin.
      Eight years before the donation, she had a mild liver dysfunction that was
      diagnosed as a hepatitis C virus (HCV) infection (serotype 2). She had received
      anti-viral therapy with interferon alpha-2b three times weekly for 24 weeks and
      had a sustained viral response (SVR). A biopsy of her liver before the donation
      showed normal findings without any active hepatitis, and her serum was negative
      for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan.
      The family in this case decided to have living donor LT. A careful selection for
      the liver graft donation was made; however, since she was the only candidate, we
      approved her as a living donor. She was discharged nine days after the liver
      donation. Her liver function recovered immediately. A computed tomography scan
      showed sufficient liver regeneration one year later. Her brother also had good
      liver function after LT and had no HCV infection 48 months after surgery and no
      de novo malignancy. Neither of the siblings has developed an HCV infection.
      CONCLUSIONS: A patient with SVR status after interferon therapy might be
      considered a candidate for living donor LT but only if there are no other
      possibilities of LT for the recipient. A careful follow-up of the donor after
      donation is needed. The recipient also must have a very close follow-up because
      it is difficult to predict what might happen to the graft with post-transplant
      immunosuppression.

PMID- 21722403
TI  - Hyperthyroidism from autoimmune thyroiditis in a man with type 1 diabetes
      mellitus: a case report.
AB  - INTRODUCTION: The presentation, diagnosis, clinical course and treatment of a man
      with hyperthyroidism secondary to autoimmune thyroiditis in the setting of type 1
      diabetes mellitus has not previously been described. CASE PRESENTATION: A 32-year
      old European-American man with an eight-year history of type 1 diabetes mellitus
      presented with an unintentional 22-pound weight loss but an otherwise normal
      physical examination. Laboratory studies revealed a suppressed thyroid
      stimulating hormone concentration and an elevated thyroxine level, which are
      consistent with hyperthyroidism. His anti-thyroid peroxidase antibodies were
      positive, and his thyroid-stimulating immunoglobulin test was negative. Uptake of
      radioactive iodine by scanning was 0.5% at 24 hours. The patient was diagnosed
      with autoimmune thyroiditis. Six weeks following his initial presentation he
      became clinically and biochemically hypothyroid and was treated with thyroxine.
      CONCLUSION: This report demonstrates that autoimmune thyroiditis presenting as
      hyperthyroidism can occur in a man with type 1 diabetes mellitus. Autoimmune
      thyroiditis may be an isolated manifestation of autoimmunity or may be part of an
      autoimmune polyglandular syndrome. Among patients with type 1 diabetes mellitus
      who present with hyperthyroidism, Graves' disease and other forms of
      hyperthyroidism need to be excluded as autoimmune thyroiditis can progress
      quickly to hypothyroidism, requiring thyroid hormone replacement therapy.

PMID- 21722404
TI  - Mycoplasma hominis brain abscess following uterus curettage: a case report.
AB  - INTRODUCTION: Mycoplasma hominis is mostly known for causing urogenital
      infections. However, it has rarely been described as an agent of brain abscess.
      CASE PRESENTATION: We describe a case of M. hominis brain abscess in a 41-year
      old Caucasian woman following uterus curettage. The diagnosis was obtained by 16S
      rDNA amplification, cloning and sequencing from the abscess pus, and confirmed by
      a specifically designed real-time polymerase chain reaction assay. CONCLUSIONS:
      Findings from our patient's case suggest that M. hominis should be considered as
      a potential agent of brain abscess, especially following uterine manipulation.

PMID- 21722405
TI  - Situs inversus totalis with perforated duodenal ulcer: a case report.
AB  - INTRODUCTION: Situs inversus is an uncommon anomaly. Situs inversus viscerum can
      be either total or partial. Total situs inversus, also termed as mirror image
      dextrocardia, is characterized by a heart on the right side of the midline while
      the liver and the gall bladder are on the left side. Patients are usually
      asymptomatic and have a normal lifespan. The exact etiology is unknown but an
      autosomal recessive mode of inheritance has been speculated. The first case of
      perforated duodenal ulcer with situs inversus was reported in 1986; here, we
      report the second case of this nature in the medical literature. CASE
      PRESENTATION: A 22-year-old Pakistani man presented with severe epigastric and
      left hypochondrial pain. Examination and investigations (chest X-ray and
      ultrasonography) confirm peritonitis in a case of situs inversus totalis. On
      exploratory laparotomy, a diagnosis of situs inversus totalis with perforated
      duodenal ulcer was confirmed. Graham's patch closure of the duodenal ulcer was
      performed with absorbable sutures, and a thorough peritoneal lavage was also
      performed; an incidental appendectomy was also performed to avoid further
      diagnostic problems. Our patient had an uneventful recovery. CONCLUSIONS: A
      diagnostic dilemma arises whenever abdominal pathology occurs in patients with
      situs inversus. Although an uncommon anomaly, to choose a proper surgical
      incision site for abdominal exploration pre-operative recognition of the
      condition is important.

PMID- 21722406
TI  - Fulminant hemophagocytic lymphohistiocytosis induced by pandemic A (H1N1)
      influenza: a case report.
AB  - INTRODUCTION: Hemophagocytic lymphohistiocytosis induced by viral diseases is a
      well recognized entity. Severe forms of H5N1 influenza are known to be associated
      with symptoms very similar to a reactive hemophagocytic syndrome. We report a
      case of fulminant lymphohistiocytosis associated with the pandemic A (H1N1)
      variant. CASE PRESENTATION: A 42-year-old Caucasian woman developed a syndrome of
      fatal hemophagocytic lymphohistiocytosis shortly after H1N1 influenza. Initial
      symptoms of the viral disease were unusual, with acute abdominal involvement. Our
      patient's course was complicated by diffuse skin rash and ileal ischemia. Our
      patient died of refractory shock and multi-organ failure. Skin, ileum and colon
      histology was consistent with an acute apoptosis combined with an increased
      cellular regeneration. CONCLUSIONS: Influenza may be complicated by severe forms
      of hemophagocytic lymphohistiocytosis. To ensure early recognition and treatment,
      physicians should be aware of the possible induction of the syndrome by the novel
      H1N1 variant. The rapid occurrence of a multi-organ involvement with evocative
      biological features of macrophage activation should alert clinicians.

PMID- 21722407
TI  - Gene set analysis for longitudinal gene expression data.
AB  - BACKGROUND: Gene set analysis (GSA) has become a successful tool to interpret
      gene expression profiles in terms of biological functions, molecular pathways, or
      genomic locations. GSA performs statistical tests for independent microarray
      samples at the level of gene sets rather than individual genes. Nowadays, an
      increasing number of microarray studies are conducted to explore the dynamic
      changes of gene expression in a variety of species and biological scenarios. In
      these longitudinal studies, gene expression is repeatedly measured over time such
      that a GSA needs to take into account the within-gene correlations in addition to
      possible between-gene correlations. RESULTS: We provide a robust nonparametric
      approach to compare the expressions of longitudinally measured sets of genes
      under multiple treatments or experimental conditions. The limiting distributions
      of our statistics are derived when the number of genes goes to infinity while the
      number of replications can be small. When the number of genes in a gene set is
      small, we recommend permutation tests based on our nonparametric test statistics
      to achieve reliable type I error and better power while incorporating unknown
      correlations between and within-genes. Simulation results demonstrate that the
      proposed method has a greater power than other methods for various data
      distributions and heteroscedastic correlation structures. This method was used
      for an IL-2 stimulation study and significantly altered gene sets were
      identified. CONCLUSIONS: The simulation study and the real data application
      showed that the proposed gene set analysis provides a promising tool for
      longitudinal microarray analysis. R scripts for simulating longitudinal data and
      calculating the nonparametric statistics are posted on the North Dakota INBRE
      website http://ndinbre.org/programs/bioinformatics.php. Raw microarray data is
      available in Gene Expression Omnibus (National Center for Biotechnology
      Information) with accession number GSE6085.

PMID- 21722408
TI  - Valproic acid inhibits neural progenitor cell death by activation of NF-kappaB
      signaling pathway and up-regulation of Bcl-XL.
AB  - BACKGROUND: At the beginning of neurogenesis, massive brain cell death occurs and
      more than 50% of cells are eliminated by apoptosis along with neuronal
      differentiation. However, few studies were conducted so far regarding the
      regulation of neural progenitor cells (NPCs) death during development. Because of
      the physiological role of cell death during development, aberration of normal
      apoptotic cell death is detrimental to normal organogenesis.Apoptosis occurs in
      not only neuron but also in NPCs and neuroblast. When growth and survival signals
      such as EGF or LIF are removed, apoptosis is activated as well as the induction
      of differentiation. To investigate the regulation of cell death during
      developmental stage, it is essential to investigate the regulation of apoptosis
      of NPCs. METHODS: Neural progenitor cells were cultured from E14 embryonic brains
      of Sprague-Dawley rats. For in vivo VPA animal model, pregnant rats were treated
      with VPA (400 mg/kg S.C.) diluted with normal saline at E12. To analyze the cell
      death, we performed PI staining and PARP and caspase-3 cleavage assay. Expression
      level of proteins was investigated by Western blot and immunocytochemical assays.
      The level of mRNA expression was investigated by RT-PCR. Interaction of Bcl-XL
      gene promoter and NF-kappaB p65 was investigated by ChIP assay. RESULTS: In this
      study, FACS analysis, PI staining and PARP and caspase-3 cleavage assay showed
      that VPA protects cultured NPCs from cell death after growth factor withdrawal
      both in basal and staurosporine- or hydrogen peroxide-stimulated conditions. The
      protective effect of prenatally injected VPA was also observed in E16 embryonic
      brain. Treatment of VPA decreased the level of IkappaBalpha and increased the
      nuclear translocation of NF-kappaB, which subsequently enhanced expression of
      anti-apoptotic protein Bcl-XL. CONCLUSION: To the best of our knowledge, this is
      the first report to indicate the reduced death of NPCs by VPA at developmentally
      critical periods through the degradation of IkappaBalpha and the activation of NF
      kappaB signaling. The reduced NPCs death might underlie the neurodevelopmental
      defects collectively called fetal valproate syndrome, which shows symptoms such
      as mental retardation and autism-like behavior.

PMID- 21722409
TI  - Metabolic responses to high protein diet in Korean elite bodybuilders with high
      intensity resistance exercise.
AB  - BACKGROUND: High protein diet has been known to cause metabolic acidosis, which
      is manifested by increased urinary excretion of nitrogen and calcium.
      Bodybuilders habitually consumed excessive dietary protein over the amounts
      recommended for them to promote muscle mass accretion. This study investigated
      the metabolic response to high protein consumption in the elite bodybuilders.
      METHODS: Eight elite Korean bodybuilders within the age from 18 to 25, mean age
      21.5 +/- 2.6. For data collection, anthropometry, blood and urinary analysis, and
      dietary assessment were conducted. RESULTS: They consumed large amounts of
      protein (4.3 +/- 1.2 g/kg BW/day) and calories (5,621.7 +/- 1,354.7 kcal/day), as
      well as more than the recommended amounts of vitamins and minerals, including
      potassium and calcium. Serum creatinine (1.3 +/- 0.1 mg/dl) and potassium (5.9 +/
      0.8 mmol/L), and urinary urea nitrogen (24.7 +/- 9.5 mg/dl) and creatinine (2.3
      +/- 0.7 mg/dl) were observed to be higher than the normal reference ranges.
      Urinary calcium (0.3 +/- 0.1 mg/dl), and phosphorus (1.3 +/- 0.4 mg/dl) were on
      the border of upper limit of the reference range and the urine pH was in normal
      range. CONCLUSIONS: Increased urinary excretion of urea nitrogen and creatinine
      might be due to the high rates of protein metabolism that follow high protein
      intake and muscle turnover. The obvious evidence of metabolic acidosis in
      response to high protein diet in the subjects with high potassium intake and
      intensive resistance exercise were not shown in this study results. However, this
      study implied that resistance exercise with adequate mineral supplementation,
      such as potassium and calcium, could reduce or offset the negative effects of
      protein-generated metabolic changes. This study provides preliminary information
      of metabolic response to high protein intake in bodybuilders who engaged in high
      intensity resistance exercise. Further studies will be needed to determine the
      effects of the intensity of exercise and the level of mineral intakes, especially
      potassium and calcium, which have a role to maintain acid-base homeostasis, on
      protein metabolism in large population of bodybuilders.

PMID- 21722410
TI  - Transgenic tobacco plants constitutively expressing Arabidopsis NPR1 show
      enhanced resistance to root-knot nematode, Meloidogyne incognita.
AB  - In Arabidopsis, non-expressor of pathogenesis related genes-1, NPR1 has been
      shown to be a positive regulator of the salicylic acid controlled systemic
      acquired resistance pathway and modulates the cross talk between SA and JA
      signaling. Transgenic plants expressing AtNPR1 constitutively exhibited
      resistance against pathogens as well as herbivory. In the present study, tobacco
      transgenic plants expressing AtNPR1 were studied further for their response to
      infection by the sedentary endoparasitic root knot nematode, Meloidogyne
      incognita. Transgenic plants showed enhanced resistance against the root-knot
      nematode infection. Prominent differences in the shoot and root weights of wild
      type and transgenic plants were observed post-inoculation with M. incognita. This
      was associated with a decrease in the number of root galls and egg masses in
      transgenic plants compared to WT. The transgenic plants also showed constitutive
      and induced expression of some PR protein genes, when challenged with M.
      incognita.

PMID- 21722412
TI  - Symbiotic association between soybean plants and Bradyrhizobium japonicum
      develops oxidative stress and heme oxygenase-1 induction at early stages.
AB  - We have previously demonstrated that the induction of heme oxygenase-1 (HO-1) (EC
      1.14.99.3) plays a protective role against oxidative stress in leaves and nodules
      of soybean plants subjected to cadmium, UV-B radiation, and salt stress. Here, we
      investigated HO-1, localization and their relationship with oxidative stress in
      different growth stages of soybean plants roots inoculated with Bradyrhizobium
      japonicum (3, 5, 7, 10, and 20 days post-inoculation) and nodules. After 7 days
      of inoculation, we observed a 70% increase in thiobarbituric acid-reactive
      substances that correlates with an enhancement in the gene expression of HO-1,
      catalase, and superoxide dismutase. Furthermore, the inhibition of HO-1 activity
      by Zn-protoporphyrin IX produced an increase in lipid peroxidation and a decrease
      in glutathione content suggesting that, in this symbiotic process, HO-1 may act
      as a signal molecule that protects the root against oxidative stress. We
      determined, for the first time, the tissular localization of HO-1 in nodules by
      electron-microscope examination. These results undoubtedly demonstrated that this
      enzyme is localized only in the plant tissue and its overexpression may play an
      important role as antioxidant defense in the plant. Moreover, we demonstrate
      that, in roots, HO-1 is induced by oxidative stress produced by inoculation of B.
      japonicum and exerts an antioxidant response against it.

PMID- 21722413
TI  - Hepatoprotective effects of saponarin, isolated from Gypsophila trichotoma Wend.
      on cocaine-induced oxidative stress in rats.
AB  - The antioxidant effect of saponarin, which is the main flavone isolated from
      Gypsophila trichotoma Wend., and its protection against cocaine hepatotoxicity
      were investigated in male Wistar rats. The animals were treated with cocaine (40
      mg/kg i.p.) alone and also after 3 consecutive days of pretreatment with
      saponarin (80 mg/kg p.o.). After 18 hours the rats were sacrificed by
      decapitation. The production of thiobarbituric acid reactive substances, reduced
      glutathione (GSH) and the activity of the following antioxidant enzymes:
      catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase,
      and glutathione-S-transferase were assessed in liver homogenate. Administered
      alone, cocaine induced significant hepatotoxicity manifested with GSH depletion
      and reduced antioxidant defences. Saponarin pretreatment, however, decreased
      cocaine toxicity both by increasing GSH levels and antioxidant enzyme activities.
      The results of this study proved the antioxidant activity of saponarin and its
      protective effect against cocaine-induced oxidative stress and hepatotoxicity.

PMID- 21722414
TI  - Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory
      activities in experimental liver fibrosis.
AB  - BACKGROUND: Experimental liver fibrosis induced by carbon tetrachloride (CCl(4))
      is associated with oxidative stress, lipid peroxidation, and inflammation. This
      work was focused on elucidating the anti-inflammatory and antioxidant effects of
      ethylenediaminetetraacetic acid (EDTA) in this model of hepatotoxicity. METHODS:
      Wistar male rats were treated with CCl(4) and EDTA (60, 120, or 240 mg/kg).
      Morphometric analyses were carried out in Masson's stained liver sections to
      determine fibrosis index. Coagulation tests prothrombin time (PT) and partial
      thromboplastin time (PTT) were also determined. Gene expression for transforming
      growth factor beta (TGF-beta1), alpha1(I) procollagen gene (alpha1 Col I), tumor
      necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase
      (SOD) was monitored by real-time PCR. Antioxidant effect of EDTA was measured by
      its effects on lipid peroxidation; biological activity of ceruloplasmin (Cp),
      SOD, and catalase (Cat) were analyzed by zymography assays. RESULTS: Animals with
      CCl(4)-hepatic injury that received EDTA showed a decrement in fibrosis (20%) and
      lipid peroxidation (22%). The mRNA expression for TNF-alpha (55%), TGF-beta1
      (50%), IL-6 (52%), and alpha1 Col I (60%) was also decreased. This group of
      animals showed increased Cp (62%) and SOD (25%) biological activities.
      Coagulation blood tests, Cat activity, and gene expression for SOD were not
      modified by EDTA treatment. CONCLUSION: This study demonstrates that EDTA
      treatment induces the activity of antioxidant enzymes, decreases lipid
      peroxidation, hepatic inflammation, and fibrosis in experimental liver fibrosis
      induced by CCl(4).

PMID- 21722415
TI  - Age-related changes in an antioxidant defense system in elderly patients with
      essential hypertension compared with healthy controls.
AB  - BACKGROUND AND AIMS: Oxidative stress has been reported to increase with aging.
      Oxidative stress is also associated with hypertension, and antioxidant treatment
      has been shown to enhance antioxidant defense system. We therefore aimed to
      analyze the relationship between aging and some markers of oxidative stress in
      elderly patients with essential hypertension compared with healthy controls.
      MATERIAL AND METHODS: Blood was collected from 18 patients with essential
      hypertension and 21 age- and sex-matched healthy controls aged over 65. Patients
      were on their usual medications while participating in the study. Oxidative
      stress parameters were investigated by measuring the concentration of glutathione
      (GSH) in whole blood and activities of glutathione peroxidase (GPx-1),
      glutathione reductase (GR), catalase (CAT), and Cu-Zn superoxide dismutase (CuZn
      SOD, SOD-1) in erythrocytes. GSH, GPx-1, GR, CAT, and CuZn SOD correlations with
      age were expressed as Pearson product-moment correlation coefficient r.
      Independent-samples T test was used to compare mean values of parameters between
      groups. RESULTS: (1) Among all parameters analyzed herein, the activity of SOD-1
      showed the most explicit decrease in relation to age, both in healthy controls
      and hypertensive subjects with r values of -0.54 (P = 0.05) and -0.68 (P < 0.01),
      respectively. (2) Age-related changes in parameters of oxidative stress did not
      differ significantly between groups. (3) Mean activity of SOD-1 was significantly
      higher (P < 0.05) in elderly hypertensives (2341.7 +/- 213.71 U/g Hb) when
      compared with healthy controls (2199.7 +/- 213.66 U/g Hb). (4) Mean GSH level was
      significantly higher (P < 0.01) in patients (3.1 +/- 0.29 mmol/l) than in
      controls (2.8 +/- 0.37 mmol/l). (5) Increased level of GSH in hypertension was
      followed by significantly (P < 0.01) higher activity of GR in this group when
      compared with controls (83.4 +/- 15.25 and 64.1 +/- 9.40 U/g Hb, respectively).
      CONCLUSIONS: (1) The antioxidant barrier changes in elderly subjects with
      senescence. (2) CuZn SOD activity is negatively correlated with age and this
      association is not altered by factors that modulate the enzyme activity, such as
      hypertension and antihypertensive treatment. (3) Significantly higher
      concentration of GSH and significantly higher GR activity in patients may suggest
      a significant role of GSH metabolism in the pathogenesis of hypertension, as well
      as its contribution to the effect of antihypertensive treatment.

PMID- 21722416
TI  - Xanthophyll cycle--a mechanism protecting plants against oxidative stress.
AB  - Six different xanthophyll cycles have been described in photosynthetic organisms.
      All of them protect the photosynthetic apparatus from photodamage caused by light
      induced oxidative stress. Overexcitation conditions lead, in the chloroplast, to
      the over-reduction of the NADP pool and production of superoxide, which can
      subsequently be metabolized to hydrogen peroxide or a hydroxyl radical, other
      reactive oxygen species (ROS). On the other hand, overexcitation of photosystems
      leads to an increased lifetime of the chlorophyll excited state, increasing the
      probability of chlorophyll triplet formation which reacts with triplet oxygen
      forming single oxygen, another ROS. The products of the light-dependent phase of
      xanthophyll cycles play an important role in the protection against oxidative
      stress generated not only by an excess of light but also by other ROS-generating
      factors such as drought, chilling, heat, senescence, or salinity stress. Four,
      mainly hypothetical, mechanisms explaining the protective role of xanthophyll
      cycles in oxidative stress are presented. One of them is the direct quenching of
      overexcitation by products of the light phase of xanthophyll cycles and three
      others are based on the indirect participation of xanthophyll cycle carotenoids
      in the process of photoprotection. They include: (1) indirect quenching of
      overexcitation by aggregation-dependent light-harvesting complexes (LHCII)
      quenching; (2) light-driven mechanisms in LHCII; and (3) a model based on charge
      transfer quenching between Chl a and Zx. Moreover, results of the studies on the
      antioxidant properties of xanthophyll cycle pigments in model systems are also
      presented.

PMID- 21722417
TI  - Electrospun biomimic nanofibrous scaffolds of silk fibroin/hyaluronic acid for
      tissue engineering.
AB  - This study aimed to fabricate nanofibrous scaffolds which could biomimic the
      natural extracellular matrix from aqueous solutions of silk fibroin and
      hyaluronic acid blends (SF/HA) by means of electrospinning. Scanning electronic
      microscopy results indicated that electrospun SF/HA nanofibers were ribbon-shaped
      and their average width obviously decreased with the increase of HA content.
      However, there is no fiber observed when the volume of HA further increased to
      50% of overall volume. After being treated with 75% ethanol vapor for 24 h, the
      fibers still remained their fibrous morphologies and presented good capability of
      water-resistance. Fourier transform infrared attenuated total reflectance
      spectroscopy, (13)C-CP-MAS nuclear magnetic resonance and differential scanning
      calorimetry results revealed that HA did not induce SF conformation from random
      coil to beta-sheet. SF conformation converted from random coil to beta-sheet
      after being treated with 75% ethanol vapor. Cell viability studies demonstrated
      that SF/HA nanofibrous scaffolds significantly promoted cell proliferation.
      Electrospun SF/HA nanofibers may provide an ideal biomimic tissue-engineering
      scaffold or vehicle for water-soluble drugs. 

PMID- 21722418
TI  - Cultured primary macrophage activation by lipopolysaccharide depends on adsorbed
      protein composition and substrate surface chemistry.
AB  - Recent efforts show that significantly reducing implant-adsorbed proteins does
      not avoid the foreign body response. Fluorinated surfaces are commonly used to
      passivate cell-mediated inflammatory responses to implanted materials but adsorb
      host proteins and facilitate the attachment and proliferation of macrophages.
      This study considers in vitro macrophage activation to fluorinated TeflonAF((r))
      compared to tissue-culture polystyrene using pre-adsorbed proteins (fibrinogen,
      BSA, collagen and elastin). Primary macrophage cultures adhere on all pre
      adsorbed protein surfaces in a protein concentration-dependent manner and
      activate to the same extent after 72 h, regardless of surface chemistry. However,
      macrophages alter their cultured adherent morphology depending on which protein
      is pre-adsorbed to these surfaces. Macrophages cultured on TeflonAF((r)) on all
      pre-adsorbed proteins produced overall higher levels of the pro-inflammatory
      cytokines - TNF-alpha, IL-6, IL-1beta or MCP-1 - than those cultured on tissue
      culture polystyrene and those cultured in serum-free media. However, at 72 h,
      macrophages adherent on BSA or fibrinogen pre-adsorbed surfaces failed to exhibit
      increased amounts of TNF-a, IL-6 or IL-1/S on either TeflonAF((r)) or TCPS, as
      well as MCP-1 on TCPS, in the presence of activating lipopolysaccharide.
      Different cell responses to pre-adsorbed proteins reflect substrate-specific
      regulation of macrophage cytokine secretion, indicative of LPS tolerance distinct
      from secondary macrophage cultures, and also distinct from macrophages adherent
      to surfaces in the absence of proteins. This result has bearing on connecting
      macrophage adhesion via adsorbed proteins on (fluorinated) biomaterials, and
      their resulting chronic activation that yields the FBR and possibly reduces
      effective macrophage clearance of microbes around implanted materials. 

PMID- 21722419
TI  - Effect of EGF and bFGF on fibroblast proliferation and angiogenic cytokine
      production from cultured dermal substitutes.
AB  - Growth factors accelerate wound healing but the underlying mechanisms remain
      poorly understood. The aim of this study was to investigate the effect of
      epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on
      fibroblast proliferation and production of angiogenic factors from cultured
      dermal substitutes (CDS). In the first experiment, fibroblasts were seeded into a
      flask at a density of 1 * 10(4) cells/cm(2).Cell proliferation was assessed after
      culturing in media containing EGF or bFGF at concentrations ranging from 2 to 50
      MUg. The number of fibroblasts increased significantly in the presence of EGF or
      bFGF, but fibroblasts detached from the flasks in the presence of 50 MUg bFGF. In
      the second experiment, CDS were prepared by incorporating fibroblasts into
      collagen gels. To make a wound surface model, the CDS was elevated to the air
      liquid interface, on which a spongy sheet of hyaluronic acid (HA) containing EGF
      or bFGF was placed. The amount of vascular endothelial growth factor (VEGF) and
      hepatocyte growth factor (HGF) released from the CDS after 1 week of cultivation
      was measured by ELISA. When the CDS was covered with a HA sponge containing EGF
      (Group 1), fibroblasts released 3.5-times more VEGF compared with a HA-alone
      sponge (control group). When covered with a HA sponge containing bFGF (Group 2),
      8.7-times more VEGF was released compared with the control group. Fibroblasts in
      Groups 1 and 2 released 9.6- and 9.3-times more HGF, respectively, compared with
      the control group. Thus, EGF stimulates fibroblasts to produce VEGF and HGF, in
      addition to its ability to enhance epidermal cell proliferation. 

PMID- 21722420
TI  - The evaluation of hydroxyl ions as a nucleating agent for apatite on electrospun
      non-woven poly( epsilon -caprolactone) fabric.
AB  - The capacity of hydroxyl ions when used as a nucleating agent to form apatite in
      simulated body fluid (SBF) was investigated. A 25 wt% poly(epsilon-caprolactone)
      solution was prepared using 1,1,3,3-hexafluoro-2-propanol as a solvent and was
      electrospun under an electric field of 1 kV/cm. Subsequently, non-woven
      poly(epsilon-caprolactone) fabrics were dipped into 4 M NaOH solution and the
      experimental group was then directly air-dried (NaOH coated), while the control
      group was washed with deionized water and air-dried (NaOH treated) under ambient
      conditions. The non-woven poly(epsilon-caprolactone) fabrics that were coated and
      treated with NaOH were exposed to SBF for 1 week, which resulted in the
      deposition of a layer of apatite crystals on the non-woven poly(epsilon
      caprolactone) fabric coated with NaOH only. On the other hand, when the non-woven
      poly(epsilon-caprolactone) fabrics were dipped into 0.05, 0.1, 1 and 4 M NaOH
      solutions, respectively, air-dried, and then soaked in SBF, the apatite forming
      capacity was gradually increased according to the concentration of NaOH solution.
      These results were explained in terms of the degree of apatite supersaturation in
      SBF induced by the release of hydroxyl ions from the coated NaOH because hydroxyl
      ions are one of the constituent elements of apatite. These results suggest that
      hydroxyl ions have a good potential for use as a nucleating agent for apatite on
      a previously non-bioactive polymer surface. 

PMID- 21722421
TI  - Bacterial cellulose: long-term biocompatibility studies.
AB  - The bacterial cellulose (BC) secreted by Gluconacetobacter xylinus is a network
      of pure cellulose nanofibres which has high crystallinity, wettability and
      mechanical strength. These characteristics make BC an excellent material for
      tissue-engineering constructs, noteworthy for artificial vascular grafts. In this
      work, the in vivo biocompatibility of BC membranes produced by two G. xylinus
      strains was analyzed through histological analysis of long-term subcutaneous
      implants in the mice. The BC implants caused a mild and benign inflammatory
      reaction that decreased along time and did not elicit a foreign body reaction. A
      tendency to calcify over time, which may be related to the porosity of the BC
      implants, was observed, especially among the less porous BC-1 implants. In
      addition, the potential toxicity of BC nanofibres - obtained by chemical
      mechanical treatment of BC membranes - subcutaneously implanted in mice was
      analysed through bone marrow flow cytometry and histological analyses. At 2 and 4
      months post-implantation, the nanofibres implants were found to accumulate
      intracellularly, in subcutaneous foamy macrophages aggregates. Moreover, no
      differences were observed between the controls and implanted animals in thymocyte
      populations and in B lymphocyte precursors and myeloid cells in the bone marrow. 

PMID- 21722422
TI  - Enzyme-catalyzed degradation of biodegradable polymers derived from trimethylene
      carbonate and glycolide by lipases from Candida antarctica and Hog pancreas.
AB  - Enzyme-catalyzed degradation of poly(trimethylene carbonate) homo-polymer (PTMC)
      and poly(trimethylene carbonate-co-glycolide) co-polymer (PTGA) was investigated
      in the presence of lipases from Candida antarctica and Hog pancreas. Degradation
      was monitored by gravimetry, size-exclusion chromatography (SEC), nuclear
      magnetic resonance (NMR), tensiometry and environmental scanning electron
      microscopy (ESEM). PTMC can be rapidly degraded by Candida antarctica lipase with
      98% mass loss after 9 days, while degradation by Hog pancreas lipase leads to 27%
      mass loss. Introduction of 16% glycolide units in PTMC chains strongly affects
      the enzymatic degradation. Hog pancreas lipase becomes more effective to PTGA co
      polymer with a mass loss of 58% after 9 days, while Candida antarctica lipase
      seems not able to degrade PTGA. Bimodal molecular weight distributions are
      observed during enzymatic degradation of both PTMC and PTGA, which can be
      assigned to the fact that the surface is largely degraded while the internal part
      remains intact. The composition of the PTGA co-polymer remains constant, and ESEM
      shows that the polymers are homogeneously eroded during enzymatic degradation.
      Contact angle measurements confirm the enzymatic degradation mechanism, i.e.,
      enzyme adsorption on the polymer surface followed by enzyme-catalyzed chain
      cleavage. 

PMID- 21722423
TI  - Curcumin-loaded N,O-carboxymethyl chitosan nanoparticles for cancer drug
      delivery.
AB  - Chitosan (CS) and its carboxymethyl derivatives are smart biopolymers that are
      non-toxic, biocompatible and biodegradable, and, hence, suitable for various
      biomedical applications, such as drug delivery, gene therapy and tissue
      engineering. Curcumin is a major chemotherapeutic agent with antioxidant, anti
      inflammatory, anti-proliferative, anticancer and antimicrobial effects. However,
      the potential of curcumin as a chemotherapeutic agent is limited by its
      hydrophobicity and poor bioavailability. In this work, we developed a
      nanoformulation of curcumin in a carboxymethyl chitosan (CMC) derivative, N,O
      carboxymethyl chitosan (N,O-CMC). The curcumin-loaded N,O-CMC (curcumin-N,O-CMC)
      nanoparticles were characterized using DLS, AFM, SEM, FT-IR and XRD. DLS studies
      revealed nanoparticles with a mean diameter of 150 +/- 30 nm. AFM and SEM
      confirmed that the particles have a spherical morphology within the size range of
      150 +/- 30 nm. Curcumin was entrapped with in N,O-CMC nanopartcles with an
      efficiency of 80%. The in vitro drug-release profile was studied at different pH
      (7.4 and 4.5) at 37 degrees C for different incubation periods with and without
      lysozyme. Cytotoxicity studies using MTT assay indicated that curcumin-N,O-CMC
      nanoparticles showed specific toxicity towards cancer cells and non-toxicity to
      normal cells. Cellular uptake of curcumin-N,O-CMC nanoparticles was analyzed by
      fluorescence microscopy and was reconfirmed by flow cytometry. Overall, these
      results indicate that like previously reported curcumin loaded O-CMC
      nanoparticles, N,O-CMC will also be an efficient nanocarrier for delivering
      curcumin to cancer cells. 

PMID- 21722424
TI  - pH-sensitive amphiphilic biodegradable graft co-polymer aggregates based on
      polyaspartamide for intracellular delivery.
AB  - A biodegradable, pH-sensitive amphiphilic co-polymer, o-(2-aminoethyl)-o'
      methylpolyethylene glycol/1-(3-aminopropyl)imidazole/lactic acid oligomers-g
      polyaspartamide (MPEG/API/LAs-g-PASPAM), was synthesized. The hydrophobic
      biodegradable poly (lactic acid) (PLA), the hydrophilic MPEG and the pH-sensitive
      API were successfully introduced into the biodegradable polysuccinimide (PSI)
      backbone by grafting. In its synthesis, the feed ratio of MPE to PLA was varied
      to provide different amphiphilic balances. FT-IR and (1)H-NMR spectroscopy were
      used to identify the chemical structure of the MPEG/API/LAs-g-PASPAM co-polymers
      synthesized. Tens to a few hundreds of nanometer-scaled aggregates, appropriate
      for intracellular drug-carrier applications, were developed in the simulated
      buffer solution, and their self-assembling behavior was significantly affected by
      the environmental pH. The size and morphology of self-aggregates were
      investigated using dynamic light scattering and transmission electron microscopy.
      The buffering effect was observed in the endosomal pH range. The drug loading and
      release experiments were conducted for a series of co-polymer aggregate systems,
      and it was noted that the release behavior was mostly governed by diffusion. The
      biodegradable kinetics was also studied to ascertain the drug-release mechanism. 

PMID- 21722425
TI  - Effect of the hydrophobic basal layer of thermoresponsive block co-polymer
      brushes on thermally-induced cell sheet harvest.
AB  - Thermoresponsive poly(benzyl methacrylate)-b-poly(N-isopropylacrylamide) (PBzMA-b
      PIPAAm) block co-polymer brush surfaces were prepared by surface-initiated two
      step reversible addition-fragmentation chain transfer radical (RAFT)
      polymerization. PBzMA brushes were fabricated on azoinitiator-immobilized glass
      substrates in the presence of dithiobenzoate (DTB) compound as a RAFT agent. The
      amount of grafted polymer was regulated by initial monomer concentrations. The
      second thermoresponsive blocks were added to the RAFT-related DTB groups located
      at PBzMA termini through the propagation of PIPAAm chains, resulting in formation
      of PBzMA-b-PIPAAm brushes. Surface characteristics of the block co-polymer
      brushes and its influence on thermally regulated cellular behavior were
      investigated using bovine carotid artery endothelial cells (BAECs), compared with
      PIPAAm brush surfaces. Cell adhesion/detachment behavior on thermoresponsive
      polymer brush surfaces significantly depended on their individual polymer
      architectures and chemical compositions of grafted polymers. Low-temperature
      treatment at 20 degrees C, below the phase-transition temperature of PIPAAm,
      induced the spontaneous detachment of adhering cells from the PBzMA-b-PIPAAm
      brush surfaces with a higher rate than that from PIPAAm brush surfaces. In
      addition, the cell-repellent effect of the hydrophobic basal layer successfully
      accelerated for harvesting BAEC sheets from the block co-polymer brush surfaces.
      Unique features of thermoresponsive block co-polymer brush architectures can be
      applied to control cell-adhesion strength for enhancing cell adhesion or
      accelerating cell detachment. 

PMID- 21722444
TI  - Impact of the GP contract on inequalities associated with influenza immunisation:
      a retrospective population-database analysis.
AB  - BACKGROUND: Influenza immunisation is recommended for all people aged >=65 years
      and younger people with particular chronic diseases. The Quality and Outcomes
      Framework (QOF) has provided new financial incentives for influenza immunisation
      since 2004. AIM: To determine the impact of the 2004 UK General Medical Services
      contract on the overall uptake of, and socioeconomic inequalities associated
      with, influenza immunisation. DESIGN AND SETTING: Retrospective general-practice
      population database analysis in 15 general practices in Scotland, UK. METHOD:
      Changes in influenza-immunisation uptake for those in at-risk groups between 2003
      2004 and 2006-2007 were measured, and variation in uptake examined using
      multilevel modelling. RESULTS: Uptake rose from 67.9% in 2003-2004 to 71.4% in
      2006-2007. The largest increases were seen in those aged <65 years with chronic
      disease, with uptake rising from 49.6% to 58.4%, but rates remained considerably
      lower than in those aged >=65 years. Differences between practices narrowed
      (median odds ratio [OR] for two patients randomly selected from different
      practices: 2.13 (95% confidence interval [CI] = 2.00 to 2.26) in 2003-2004 versus
      1.44 (95% CI = 1.40 to 1.49) in 2006-2007. However, inequalities in uptake by
      patient socioeconomic status did not change: adjusted OR for most deprived versus
      most affluent was 0.75 (95% CI = 0.70 to 0.80) in 2003-2004 versus 0.72 (95% CI =
      0.68 to 0.76) in 2006-2007. CONCLUSION: Overall uptake rose significantly and
      differences between practices narrowed considerably. However, socioeconomic and
      age inequalities in influenza immunisation persisted in the first 3 years of the
      QOF. This contrasts with other ecological analyses, which have concluded that the
      QOF has reduced inequalities. The impact of financial incentives on inequalities
      is likely to vary, and some kinds of care may require more targeted improvement
      activity and support.

PMID- 21722445
TI  - Parental reasons for non-uptake of influenza vaccination in young at-risk groups:
      a qualitative study.
AB  - BACKGROUND: Uptake rates of influenza vaccination in young at-risk groups in
      primary care (UK) are known to be poor. AIM: To explore parental reasons for non
      uptake of influenza vaccination in young at-risk groups. The study hypothesis was
      that exploration of parental reasons for non-uptake may reveal important barriers
      to an effective influenza vaccination programme. DESIGN AND SETTING: Thematic
      analysis of a questionnaire survey with interview follow-up at a single general
      practice in Inverness, Scotland. METHOD: Parents of children identified as being
      in an at-risk group for influenza vaccination but who had not received
      vaccination were sent questionnaires and offered the opportunity to take part in
      a follow-up interview. RESULTS: Several key themes emerged, including uncertainty
      about the indication for vaccination, issues of choice, challenges with access,
      lack of parental priority, and issues relating to health beliefs. CONCLUSION: Any
      attempt to improve the vaccination rate needs to address the range of decision
      making processes undertaken by parents and children. Better and more tailored
      information and educational delivery to parents, patients, and healthcare
      providers may lead to an increase in the rates of influenza vaccination uptake in
      at-risk children. Access is a barrier described by some parents.

PMID- 21722446
TI  - Childhood swine flu vaccination uptake in a Welsh general practice: a prospective
      study.
AB  - BACKGROUND: Immunisation of infants is effective and benefits the health of the
      children immunised as well as the community where uptake is high. Any social
      inequality in uptake will worsen any social inequalities that already exist. AIM:
      To investigate the demographic characteristics of families attending for swine
      flu vaccination. DESIGN AND SETTING: A prospective study in a semi-rural general
      practice in South Wales. METHOD: Data were collected by questionnaire, and
      logistic regression models were used to test for associations between potential
      risk factors (including family demographic characteristics and the child's
      previous vaccination history) and swine flu vaccination uptake. RESULTS: No
      evidence was found of any significant associations between potential risk factors
      and the outcome. CONCLUSION: This suggests that social inequality did not affect
      vaccination uptake in this sample.

PMID- 21722447
TI  - Trends in doctors' early career choices for general practice in the UK:
      longitudinal questionnaire surveys.
AB  - BACKGROUND: The percentage of newly qualified doctors in the UK who want a career
      in general practice declined substantially in the 1990s. The English Department
      of Health expects that half of all doctors will become GPs. AIM: To report on
      choices for general practice made by doctors who qualified in 2000, 2002, 2005,
      2008, and 2009. DESIGN AND SETTING: A structured, closed questionnaire about
      future career intentions, sent to all UK medical graduates. METHOD:
      Questionnaires sent 1 year after qualification (all cohorts) and 3 years after
      (all except 2008 and 2009). RESULTS: Percentages of doctors who expressed an
      unreserved first choice for general practice in the first year after
      qualification, in the successive five cohorts, were 22.2%, 20.2%, 23.2%, 21.3%,
      and 20.4%. Percentages who expressed any choice for general practice - whether
      first, second or third - were 46.5%, 43.4%, 52.6%, 49.5%, and 49.9%. Three years
      after qualification, an unreserved first choice was expressed, in successive
      cohorts, by 27.9%, 26.1%, and 35.1%. Doctors from newly established English
      medical schools showed the highest levels of choice for general practice.
      CONCLUSION: The percentage of doctors, in their first post-qualification year,
      whose first choice of eventual career was general practice has not changed much
      in recent years. By year 3 after qualification, this preference has increased in
      recent years. At years 1 and 3, the overall first choice for general practice is
      considerably lower than the required 50%, but varies substantially by medical
      school. In depth studies of why this is so are needed.

PMID- 21722448
TI  - Resilience among doctors who work in challenging areas: a qualitative study.
AB  - BACKGROUND: Although physician burnout has received considerable attention, there
      is little research of doctors who thrive while working in challenging conditions.
      AIM: To describe attitudes to work and job satisfaction among Australian primary
      care practitioners who have worked for more than 5 years in areas of social
      disadvantage. METHOD: Semi-structured interviews were conducted with 15 primary
      health care practitioners working in Aboriginal health, prisons, drug and alcohol
      medicine, or youth and refugee health. The interviews explored attitudes towards
      work and professional satisfaction, and strategies to promote resilience.
      RESULTS: All doctors were motivated by the belief that helping a disadvantaged
      population is the 'right thing' to do. They were sustained by a deep appreciation
      and respect for the population they served, an intellectual engagement with the
      work itself, and the ability to control their own working hours (often by working
      part-time in the field of interest). In their clinical work, they recognised and
      celebrated small gains and were not overwhelmed by the larger context of social
      disadvantage. CONCLUSION: If organisations want to increase the numbers of
      medical staff or increase the work commitment of staff in areas of social
      disadvantage, they should consider supporting doctors to work part-time, allowing
      experienced doctors to mentor them to model these patient-appreciative
      approaches, and reinforcing, for novice doctors, the personal and intellectual
      pleasures of working in these fields.

PMID- 21722449
TI  - Attracting and retaining GPs: a stakeholder survey of priorities.
AB  - BACKGROUND: Despite being a key player in the healthcare system, training and
      practising general practice has become less attractive in many countries and is
      in need of reform. AIM: To identify political priorities for improving GPs'
      attraction to the profession and their retention within it. DESIGN AND SETTING:
      Stakeholder face-to-face survey in Belgium, 2008. METHOD: A total of 102 key
      stakeholders were recruited from policymakers, professional groups, academia, GP
      leaders, and the media. All interviewees were asked to score 23 policies on four
      criteria: effectiveness in attracting and retaining GPs, cost to society,
      acceptance by other health professionals, and accessibility of care. An overall
      performance score was computed (from -3 to +3) for each type of policy -
      training, financing, work-life balance, practice organisation, and governance -
      and for innovative versus conservative policies. RESULTS: Practice organisation
      policies and training policies received the highest scores (mean score >= 1.11).
      Financing policies, governance, and work-life balance policies scored poorly
      (mean score <= 0.65) because they had negative effects, particularly in relation
      to cost, acceptance, and accessibility of care. Stakeholders were keen on moving
      GPs towards team work, improving their role as care coordinator, and helping them
      to offload administrative tasks (score >= 1.4). They also favoured moves to
      increase the early and integrated exposure of all medical students to general
      practice. Overall, conservative policies were better scored than innovative ones
      (beta = -0.16, 95% confidence interval = -0.28 to -0.03). CONCLUSION: The
      reforming of general practice is made difficult by the small-step approach, as
      well as the importance of decision criteria related to cost, acceptance, and
      access.

PMID- 21722450
TI  - Measuring depression severity in general practice: discriminatory performance of
      the PHQ-9, HADS-D, and BDI-II.
AB  - BACKGROUND: The UK Quality and Outcomes Framework (QOF) rewards practices for
      measuring symptom severity in patients with depression, but the endorsed scales
      have not been comprehensively validated for this purpose. AIM: To assess the
      discriminatory performance of the QOF depression severity measures. DESIGN AND
      SETTING: Psychometric assessment in nine Scottish general practices. METHOD:
      Adult primary care patients diagnosed with depression were invited to
      participate. The HADS-D, PHQ-9, and BDI-II were assessed against the HRSD-17
      interview. Discriminatory performance was determined relative to the HRSD-17 cut
      offs for symptoms of at least moderate severity, as per criteria set by the
      American Psychiatric Association (APA) and NICE. Receiver operating
      characteristic curves were plotted and area under the curve (AUC), sensitivity,
      specificity, and likelihood ratios (LRs) calculated. RESULTS: A total of 267 were
      recruited per protocol, mean age = 49.8 years (standard deviation [SD] = 14.1),
      70% female, mean HRSD-17=12.6 (SD = 7.62, range = 0-34). For APA criteria, AUCs
      were: HADS-D = 0.84; PHQ-9 = 0.90; and BDI-II = 0.86. Optimal sensitivity and
      specificity were reached where HADS-D >=9 (74%, 76%); PHQ-9 >=12 (77%, 79%), and
      BDI-II >=23 (74%, 75%). For NICE criteria: HADS-D AUC = 0.89; PHQ-9 AUC = 0.93;
      and BDI-II AUC = 0.90. Optimal sensitivity and specificity were reached where
      HADS-D >=10 (82%, 75%), PHQ-9 >=15 (89%, 83%), and BDI-II >=28 (83%, 80%). LRs
      did not provide evidence of sufficient accuracy for clinical use. CONCLUSION: As
      selecting treatment according to depression severity is informed by an evidence
      base derived from trials using HRSD-17, and none of the measures tested aligned
      adequately with that tool, they are inappropriate for use.

PMID- 21722451
TI  - Diagnostic triage and the role of natriuretic peptide testing and
      echocardiography for suspected heart failure: an appropriateness ratings
      evaluation by UK GPs.
AB  - BACKGROUND: Some UK GPs are acquiring access to natriuretic peptide (NP) testing
      or echocardiography as diagnostic tests for heart failure. This study developed
      appropriateness ratings for the diagnostic application of these tests in routine
      general practice. AIM: To develop appropriateness ratings for the diagnostic
      application of NP testing or echocardiography for heart failure in general
      practice. DESIGN AND SETTING: An appropriateness ratings evaluation in UK general
      practice. METHOD: Four presenting symptoms (cough, bilateral ankle swelling,
      dyspnoea, fatigue), three levels of risk of cardiovascular disease (low,
      intermediate, high), and dichotomous categorisations of cardiovascular/chest
      examination and electrocardiogram result, were used to create 540 appropriateness
      scenarios for patients in whom NP testing or echocardiography might be
      considered. These were rated by a 10-person expert panel, consisting of GPs and
      GPs with specialist interests in cardiology, in a two-round RAND Appropriateness
      Method. RESULTS: Onward referral for NP testing or echocardiography was rated as
      an appropriate next step in 217 (40.2%) of the 540 scenarios; in 194 (35.9%) it
      was rated inappropriate. The ratings also show where NP testing or
      echocardiography were ranked as equivalent next steps and when one test was seen
      as the more appropriate than the other. CONCLUSION: NP testing should be the
      routine test for suspected heart failure where referral for diagnostic testing is
      considered appropriate. An abnormal electrocardiogram status makes referral to
      echocardiography an accompanying, or more appropriate, next step alongside NP
      testing, especially in the presence of dyspnoea. Abnormal NP testing should
      subsequently be followed up with referral for echocardiography.

PMID- 21722453
TI  - Influenza vaccine uptake: the case for universal flu vaccination of young
      children.

PMID- 21722454
TI  - Future-proofing primary health care: GP recruitment and retention in the new NHS.

PMID- 21722455
TI  - The QOF, NICE, and depression: a clumsy mechanism that undermines clinical
      judgment.

PMID- 21722456
TI  - Sleep apnoea: no laughing matter.

PMID- 21722457
TI  - Screening and identifying diabetes in optometric practice: a prospective study.
AB  - BACKGROUND: Unconventional settings, outside general medical practice, are an
      underutilised resource in the attempt to identify the large numbers of people
      with undiagnosed diabetes worldwide. AIM: The study investigated the feasibility
      of using optometry practices (opticians) as a setting for a diabetes screening
      service. DESIGN AND SETTING: Adults attending high street optometry practices in
      northern England who self-reported at least one risk factor for diabetes were
      offered a random capillary blood glucose (rCBG) test. Those with raised rCBG
      levels were asked to visit their GP for further investigations. RESULTS: Of 1909
      adults attending practices for sight tests, 1303 (68.2%) reported risk factors
      for diabetes, of whom 1002 (76.9%) had rCBG measurements taken. Of these, 318
      (31.7%) were found to have a rCBG level of >=6.1 mmol/l, a level where further
      investigations are recommended by Diabetes UK; 1.6% of previously undiagnosed
      individuals were diagnosed with diabetes or pre-diabetes as a result of the
      service. Refining the number of risk factors for inclusion would have reduced
      those requiring screening by half and still have identified nearly 70% of the new
      cases of diabetes and pre-diabetes. CONCLUSION: Screening in optometric practices
      provides an efficient opportunity to screen at-risk individuals who do not
      present to conventional medical services, and is acceptable and appropriate.
      Optometrists represent a skilled worldwide resource that could provide a
      screening service. This service could be transferable to other settings.

PMID- 21722458
TI  - HIV: low prevalence is no excuse for not testing.

PMID- 21722459
TI  - How to protect general practice from child protection.

PMID- 21722460
TI  - 'Heartsink' patients in general practice.

PMID- 21722461
TI  - Validity of diagnoses in the general practice research database.

PMID- 21722462
TI  - Improving cancer outcomes.

PMID- 21722463
TI  - Improving cancer outcomes.

PMID- 21722464
TI  - GPs' views in five European countries of interventions to promote prudent
      antibiotic use.

PMID- 21722465
TI  - GPs at the deep end.

PMID- 21722466
TI  - The diagnostic value of symptoms for colorectal cancer in primary care.

PMID- 21722467
TI  - The diagnostic value of symptoms for colorectal cancer in primary care.

PMID- 21722468
TI  - Minimal undergraduate teaching curriculum in Europe.

PMID- 21722470
TI  - Public health medicine skills in the NHS: vital and very vulnerable.

PMID- 21722469
TI  - Impact of the pay-for-performance contract and the management of hypertension in
      Scottish primary care: a 6-year population-based repeated cross-sectional study.
AB  - BACKGROUND: The 2004 introduction of the pay-for-performance contract has
      increased the proportion of income that GPs are able to earn by targeting quality
      care to patients with chronic diseases such as hypertension. AIM: To investigate
      the impact of pay for performance on the management of patients with hypertension
      in Scottish primary care. DESIGN AND SETTING: A population-based repeated cross
      sectional study in Scottish primary care practices (n = 315) contributing to the
      Primary Care Clinical Informatics Unit database. METHOD: A dataset was extracted
      on 826 973 patients aged >=40 years including, age, sex, socioeconomic
      deprivation status, hypertension diagnosis, recorded blood pressure measurement,
      attainment of target blood pressure levels, and provision of hypertension-related
      prescribing for each year from 2001 until 2006. RESULTS: Increasing treatment for
      hypertension (absolute difference [AD] 9.2%; 95% confidence interval [CI] = 9.0
      to 9.5) occurred throughout the study period. The majority of increases found in
      blood pressure measurement (AD 46.8%; 95% CI = 46.5 to 47.1) and recorded
      hypertension (AD 5.9%; 95% CI = 5.7 to 6.0) occurred prior to 2004. Blood
      pressure control increased throughout the study period (absolute increase
      <=140/90 mmHg; 18.9%; 95% CI = 18.5 to 19.4). After 2004, the oldest female, as
      well as the male and female patients with the greatest socioeconomic deprivation
      status, became less likely than their youngest (<40 years) and most affluent
      counterparts to have a blood pressure measurement recorded (P<0.05). Patients not
      prescribed therapy were younger and had higher blood pressure levels (P<0.001).
      CONCLUSION: It is likely that the continued efforts of general practice to
      improve hypertension diagnosis, monitoring, and treatment will reduce future
      cardiovascular events and mortality in those with hypertension. However, there is
      a need to follow up patients who are older and more socioeconomically deprived
      once they are diagnosed, as well as prescribing antihypertensive therapy to
      younger patients, who are likely to benefit from early intervention.

PMID- 21722471
TI  - The Keppoch Medical Practice: reporting from the Deep End.

PMID- 21722472
TI  - Five-year training: a radical rational approach to delivery.

PMID- 21722473
TI  - Warehousing.

PMID- 21722476
TI  - The role of patients in UK primary care: from the extraordinary to the essential.

PMID- 21722477
TI  - Putting patients at the centre of health care in the US.

PMID- 21722478
TI  - Is patient-centred care a tautology? View from the Netherlands.
      T.J.M.Verheij@umcutrecht.nl.

PMID- 21722479
TI  - Diagnosis and assessment of food allergy in children and young people in primary
      care and community settings: NICE clinical guideline.

PMID- 21722480
TI  - Tips for GP trainees working in genitourinary medicine.

PMID- 21722481
TI  - Perspectives for the use of plant extracts to control the cattle tick
      Rhipicephalus (Boophilus) microplus.
AB  - The evolution of resistance of Rhipicephalus (Boophilus) microplus to synthetic
      acaricides has given rise to the need for new scientific investigations on
      alternative ways to control this tick. In this regard, various studies on plants
      have been developed in an attempt to find extracts with acaricidal properties.
      Evaluations on plant extracts for controlling R. (B.) microplus have grown
      intensely over the last decade. There are many advantages from using plant
      extracts: for example, they can be used in organic cattle farming or even replace
      synthetic acaricides and they are associated with lower environmental and food
      contamination, slower development of resistance and lower toxicity to animals and
      humans. In vitro studies on plant extracts have shown promising results, but most
      of these extracts have not been tested on animals to validate their use.
      Difficulties in preparing proper formulations, differences in the chemical
      composition of plants of the same species due to extrinsic and intrinsic factors
      and sparse information on active acaricide compounds are hindrances that need to
      be addressed in order to enable progress within this scientific field.

PMID- 21722482
TI  - Presence of amastigotes in the central nervous system of hamsters infected with
      Leishmania sp.
AB  - Visceral leishmaniasis (VL) is a severe chronic disease caused by Leishmania
      (Leishmania) infantum chagasi. Better knowledge on the effects caused by this
      disease can help develop adequate clinical management and treatment.
      Parasitological and immunohistochemical studies were performed golden hamsters
      Mesocricetus auratus infected with bone marrow from individuals with VL in the
      State of Mato Grosso do Sul, central-west Brazil. The effects of parasitism in
      the spleen, liver, kidneys, lungs, heart and brain of the animals were examined.
      Eighteen hamsters were inoculated intraperitoneally, and six healthy animals were
      used as negative controls. The animals were kept in the animal house and checked
      for clinical signs. Specimens of each organ were examined for the presence of
      amastigotes. Immunohistochemical technique was performed in all brain specimens
      and organs negative on the direct examination of parasites. Direct examination of
      amastigotes was positive in the spleen and liver of all infected animals; 33.3%
      showed the parasite in the kidneys and lungs, and 16.7% in the heart. Parasitic
      forms were seen in 83.3% (15/18) of the brain examined. Immunohistochemistry
      confirmed the results of the direct examination, except in two specimens of lung
      tissue and in the brain specimens. Other studies are needed to further clarify
      the effect of the parasite in the central nervous system.

PMID- 21722483
TI  - Rhipicephalus (Boophilus) microplus: expression and characterization of Bm86-CG
      in Pichia pastoris.
AB  - The cattle tick Rhipicephalus (Boophilus) microplus is responsible for great
      economic losses. It is mainly controlled chemically, with limitations regarding
      development of resistance to the chemicals. Vaccines may help control this
      parasite, thereby reducing tick pesticide use. In this light, we performed
      subcloning of the gene of the protein Bm86-GC, the homologue protein that
      currently forms the basis of vaccines (Gavac(TM) and TickGard(PLUS)) that have
      been developed against cattle ticks. The subcloning was done in the pPIC9
      expression vector, for transformation in the yeast Pichia pastoris. This protein
      was characterized by expression of the recombinant Mut+ strain, which expressed
      greater quantities of protein. The expressed protein (rBm86-CG) was recognized in
      the Western-blot assay using anti-Gavac, anti-TickGard, anti-larval extract and
      anti-rBm86-CG polyclonal sera. The serum produced in cattle vaccinated with the
      antigen CG rBm86 presented high antibody titers and recognized the native
      protein. The rBm86-GC has potential relevance as an immunogen for vaccine
      formulation against cattle ticks.

PMID- 21722484
TI  - Presence of antibodies against Toxoplasma gondii, Neospora caninum and Leishmania
      infantum in dogs from Piaui.
AB  - This study aimed to evaluate the presence of antibodies against Neospora caninum,
      Toxoplasma gondii and Leishmania infantum in dogs attended at the Veterinary
      Hospital of the Federal University of Piaui, Northeastern Brazil, where there are
      no reports of the occurrence of N. caninum and T. gondii in dogs. Serum samples
      from 530 dogs of genders, different ages and breeds from the municipality of
      Teresina and nearby towns were analyzed using three indirect fluorescent antibody
      tests, each one targeting one of the three agents. The associations between the
      parasites and gender, breed and age of the dogs were assessed by the chi-square
      test (p > 0.05). The occurrence of antibodies to N. caninum, T. gondii and L.
      infantum was 3.2, 18.0 and 78.1%, respectively. Toxoplasma gondii was more
      frequently found in older dogs (p < 0.05) whereas L. infantum was more common in
      animals aged between 1 to 3 years (p < 0.05). In order to evaluate potential
      associations between the presence of anti-N. caninum and anti-T. gondii
      antibodies and Leishmania infection, 240 dogs were selected (120 positive and 120
      negative for Leishmania spp.), based on serological and parasitological
      diagnoses. No association was found between Leishmania spp. and the coccidian
      parasites (p > 0.05). The results confirm the exposure of dogs to these parasites
      in the State of Piaui.

PMID- 21722485
TI  - Anthelmintic resistance in a dairy cattle farm in the State of Minas Gerais.
AB  - Eighty-four half-blood Gir * Holstein (F1) calves aged six months who were
      naturally infected by gastrointestinal helminths and maintained in rotational
      grazing received different anthelmintic treatments. Group A received
      anthelmintics according to the usual management in the property (eight
      treatments, seven including a macrocyclic lactone agent). Group B received
      strategic treatment (ivermectin 3.15%) at the beginning and at the end of the
      rainy period. Eggs per gram of feces (EPG) counts and genus of larvae from fecal
      cultures were determined on a monthly basis from April 2002 to December 2003.
      There was no significant reduction (p > 0.05) in EPG counts in any group after
      anthelminthic treatment, and the larvae in fecal cultures observed were Cooperia,
      Haemonchus, Oesophagostomum and a few Trichostrongylus. Cooperia was the most
      prevalent genus in the first four months of the experiment and Haemonchus in the
      following months. In 2003, tracer calves were introduced onto the pastures
      monthly and they showed high nematode burden many times throughout the year, and
      Cooperia punctata and Haemonchus contortus were the main species identified. The
      results suggest that there is anthelminthic resistance in this farm, mainly to
      macrocyclic lactones, and the development of immunity by crossbred animals was
      vital to reduce nematode burden.

PMID- 21722486
TI  - Systemic inflammatory response indicators in rabbits (Oryctolagus cuniculus)
      experimentally infected with sporulated oocysts of Eimeria stiedai (Apicomplexa:
      Eimeriidae).
AB  - Hemograms and acute-phase proteins in adult male New Zealand White rabbits that
      had been experimentally infected orally with sporulated oocysts of Eimeria
      stiedai were evaluated over a 28-day period. Fifty animals were used, divided
      into two groups: group A infected with 1 * 10(4) sporulated oocysts of E. stiedai
      and group B inoculated with distilled water. On the seventh day after infection,
      the infected animals presented anemia and leukocytosis with neutrophilia and
      monocytosis. Protein fractionation by means of electrophoresis identified 19
      acute-phase proteins with molecular weights ranging from 24 to 238 kD.
      Ceruloplasmin, transferrin and haptoglobin showed high levels on the seventh day
      after infection, with gradual increases in their concentrations until the end of
      the experimental period. Thus, from the data of the present study, E. stiedai is
      considered to be a pyogenic etiological agent for which the infection level can
      be monitored through the leukocyte count and serum concentrations of
      ceruloplasmin, transferrin and haptoglobin, and these can be recommended as
      complementary tests.

PMID- 21722487
TI  - Acaricide resistance of Rhipicephalus (Boophilus) microplus in State of Mato
      Grosso do Sul, Brazil.
AB  - This study was conducted to obtain an epidemiological view of acaricide
      resistance in populations of Rhipicephalus (Boophilus) microplus in the State of
      Mato Grosso do Sul. Twenty-four tick samples were collected from municipalities
      in the State where farmers had reported concerns about resistance to or failure
      of tick control. These ticks were subjected to in vitro resistance detection
      assays using the adult immersion test (AIT). The efficacy of alpha-cypermethrin,
      cypermethrin and amitraz treatments on samples collected throughout the State was
      generally poor. AIT showed efficacy >= 90% from the use of DDVP +
      chlorfenvinphos) (20 out of 21 municipalities), dichlorvos + cypermethrin (10 out
      of 16 municipalities) and cypermethrin + citronella + chlorpyrifos + piperonyl
      butoxide (20 out of 21 municipalities). PCR assays were used to detect the
      presence of pyrethroid resistance-associated sodium channel gene mutation. Larvae
      from three different populations that had previously been diagnosed as pyrethroid
      resistant, through AIT, were evaluated. The PCR assays showed that the pyrethroid
      resistance-associated gene mutation was absent from these three populations. This
      study confirms that the emergence of resistance is a constant challenge for the
      livestock industry, and that development of resistance continues to be a major
      driver for new antiparasitic drugs to be developed.

PMID- 21722488
TI  - Natural infection by Eimeria spp. in a cohort of lambs raised extensively in
      Northeast Brazil.
AB  - The aim of the study was to examine and describe the changes in the course of
      Eimeria infection in a cohort of lambs of the mixed breed Santa Ines raised
      extensively on a farm in the State of Rio Grande do Norte, northeastern Brazil.
      The study was carried out between April and August 2008, during which period
      fecal samples were collected on a weekly basis from each of the 27 male lambs
      starting from the day after birth until the age of 90 days. Samples were analyzed
      under optical microscope a nd those testing positive for Eimeria oocysts were
      submitted to a quantitative analysis. Oocysts were detected in 17% of the lambs
      by week 3, but by week 6 100% of the animals were infected. Eight species of
      Eimeria were identified in the fecal samples, namely, in decreasing order of
      prevalence, E. crandallis, E. parva, E. granulosa, E. ovinoidalis, E. ahsata, E.
      ovina, E. faurei and E. intricata. Of the 191 fecal samples that contained
      Eimeria oocysts, only 32 (16.8%) were infected with a single species whereas 23
      (12.0%) were infected with at least two species and 136 (71.2%) harbored three or
      more species. Although Eimeria coccidiosis is a complex disease owing to the
      mixed nature of the infective agents, an ongoing prevention program should be
      implemented to reduce production losses.

PMID- 21722489
TI  - Prevalence of Cryptosporidium spp. and Giardia spp., spatial clustering and
      patterns of shedding in dairy calves from Cordoba, Argentina.
AB  - The objectives of this study were to estimate calf and herd prevalence of
      Cryptosporidium spp. and Giardia spp., the herd prevalence clustering, spatial
      distribution according to soil type and shedding patterns in dairy calves from
      Cordoba, Argentina. Six hundred twenty calves younger than 7 weeks of age from 43
      dairy herds were sampled. Samples were processed with the formol-ether and
      modified Ziehl-Neelsen techniques. Univariate analysis and Kruskall-Wallis tests
      were used. Factors associated were subjected to multivariate analysis with calf
      shedding intensity as the response variable. Clustering of herd prevalence was
      assessed by a scan method, and spatial analysis was applied to explore the
      overlapping of high prevalence herds and soil type. Overall calf prevalence for
      Cryptosporidium spp. oocysts and Giardia spp. cysts were 19.35% (95% CI: 16.14;
      22.54) and 34.50% (95% CI: 30.69; 38.34), respectively. Calves younger than two
      weeks of age were almost four times more likely to be infected with
      Cryptosporidium, in comparison to older ones (RR: 3.78, 95% CI: 2.27; 6.26).
      Giardia spp. shedding showed a similar age pattern (RR: 1.33, 95% CI: 1.02;
      1.75). A primary cluster of high Cryptosporidium prevalence was found, and high
      prevalence herds were located in areas with poor drained soil.

PMID- 21722490
TI  - Strategic control of cattle ticks: milk producers' perceptions.
AB  - In order to evaluate milk producers' knowledge about tests on tick sensitivity to
      acaricides, efficiency tests and strategic control, questionnaires were delivered
      to 670 producers. From these, 163 responses were received. These producers had
      sent ingurgitated female ticks to be subjected to tests on tick sensitivity to
      acaricides at Embrapa between 2001 and 2005. Most of the completed questionnaires
      came from the State of Minas Gerais, Brazil. After descriptive analysis and
      correlation of variables, it was found that 48.5% of the properties owned herds
      of up to 100 head of cattle and 57.3% of the producers belonged to a cooperative.
      Among the respondents, 157 (98.7%) applied the acaricide indicated by the
      efficiency test, and 144 (92.9%) said that they applied strategic control but
      incorrectly. There was improvement in some control stages. However, only 12 (7%)
      showed comprehension of all the stages of strategic control. It was concluded
      that there is a need for continuing assistance, so as to achieve effective
      improvement in controlling Rhipicephalus (Boophilus) microplus.

PMID- 21722491
TI  - Effect of six tropical tanniferous plant extracts on larval exsheathment of
      Haemonchus contortus.
AB  - Tanniferous plants represent a promising alternative for controlling
      gastrointestinal nematodes of small ruminants. This experiment evaluated the
      effects of extracts from the leaf and stem of Anadenanthera colubrina, Leucaena
      leucocephala and Mimosa tenuiflora on larval exsheathment of Haemonchus contortus
      in vitro and verified the role of tannins in this process. Third-stage larvae of
      H. contortus were incubated with extracts for 3 hours and were exposed to sodium
      hypochlorite solution. The extracts were tested at 300 MUg.mL(-1) and accompanied
      by controls: phosphate buffer solution (PBS) and polyvinyl polypyrrolidone
      (PVPP). The larval exsheathment was evaluated for 60 minutes, and the results
      were subjected to the Kruskal-Wallis test (p < 0.05). The six extracts blocked
      larval exsheathment. After PVPP addition, a tannin inhibitor, the exsheathment
      percentage was similar to the PBS (p > 0.05), except for L. leucocephala and M.
      tenuiflora leaf extracts. However, pre-incubation with PVPP of these two extracts
      significantly changed larval exsheathment when compared to the non-treated
      extracts (p < 0.05). These results suggest that A. colubrina, L. leucocephala and
      M. tenuiflora could be useful in gastrointestinal nematode control and that
      tannins are probably the main compounds involved in the observed effects.
      However, in vivo and toxicological studies should be conducted.

PMID- 21722492
TI  - Metacestodes of Glossocercus auritus (Cyclophyllidea, Gryporhynchidae) in
      Poecilia reticulata (Pisces, Poeciliidae) from Brazil.
AB  - Studies on fish parasites in Pampulha dam, Belo Horizonte, Minas Gerais, Brazil,
      found specimens of Poecilia reticulata Peters, 1859 harboring natural infection
      by larval stages of tapeworms. A total of 250 specimens of P. reticulata were
      collected and analyzed between February and August 2010, of which 23 were found
      infected (prevalence 9.2%) with one metacestode each (mean intensity 1, mean
      abundance 0.09). The analyses of the parasites, particularly the morphology of
      rostellar hooks, made it possible to identify Glossocercus auritus (Rudolphi,
      1818). This is the first report of G. auritus metacestode in South America and P.
      reticulata is a newly known host for this parasite.

PMID- 21722493
TI  - Phlebotomine fauna (Diptera: Psychodidae: Phlebotominae) in a residential area
      and in a fragment of savanna vegetation in the municipality of Pontal do
      Araguaia, Mato Grosso, Brazil.
AB  - Identification of phlebotomine species in endemic areas is fundamental for
      analyzing the eco-epidemiological determinants of leishmaniasis. This study had
      the aim of investigating the phlebotomine fauna in an urban area and in a
      fragment of native savanna in the municipality of Pontal do Araguaia, State of
      Mato Grosso, Brazil, using CDC light traps. One hundred and twenty-three
      phlebotomine specimens belonging to seventeen different species were caught. Our
      results indicate synanthropic potential among vector species for leishmaniasis,
      such as the species Lutzomyia cruzi, L. sallesi and L. whitmani. The species L.
      cerradincola had never been recorded in this region, such that this is the first
      report of this species in the State of Mato Grosso.

PMID- 21722494
TI  - Mesocestoides sp. (Eucestoda, Mesocestoididae) parasitizing four species of wild
      felines in Southern Brazil.
AB  - Leopardus colocolo, Leopardus geoffroyi, Leopardus tigrinus and Puma yagouaroundi
      are wild feline species endangered mainly due to habitat destruction and vehicle
      run overs. Seventeen felines hit on the roads were collected in Southern Brazil
      and examined for parasites. Cestodes were identified as Mesocestoides sp. The
      parasites were found in the small intestine of the hosts with a prevalence of
      66.7% (L. colocolo and L. tigrinus), 60% (P. yagouaroundi) and 50% (L.
      geoffroyi). Rodents and lizards were found in the stomach contents and they
      possibly were intermediate hosts of Mesocestoides sp. This is the first report of
      Mesocestoides sp. in wild felines in Brazil.

PMID- 21722495
TI  - Field study on the efficacy of an oral 2% ivermectin formulation in horses.
AB  - Twenty horses naturally infected with nematodes were included in a blind,
      controlled field study on efficacy and safety of an oral 2% ivermectin
      formulation at a dose of 0.2 mg.kg(-1). Horses were divided into treated and non
      treated (control) groups with ten animals each based on preliminary counts of
      eggs per gram of feces (EPG). Stool samples were collected after treatment for
      identification of nematode species. Clinical evaluations and EPG counts were
      performed on days 0, +5, +14 and +19. Nineteen nematode species were identified:
      Coronocyclus ulambajari, Craterostomum acuticaudatum, Cyathostomum catinatum,
      Cyathostomum pateratum, Cylicocyclus brevicapsulatus, Cylicocyclus insigne,
      Cylicocyclus leptostomum, Cylicocyclus nassatus, Cylicocyclus ultrajectinus,
      Cylicocyclus spp., Cylicostephanus calicatus, Cylicostephanus longibursatus,
      Cylicostephanus poculatus, Habronema muscae, Habronema spp., Parascaris equorum,
      Poteriostomum imparidentatum, Oxyuris equi and Triodontophorus spp. The mean EPG
      counts of treated and non-treated (control) groups on Days ?15, 0, +5, +14 and
      +19 were 1925, 1340, 0, 12.5, 0, 1470, 790, 875, 1605 and 1240 respectively. The
      efficacy of treatment on Days +5, +14 and +19 was 100, 99.2 and 100%
      respectively, with a significant difference compared to the control group (p <
      0.01). The product was considered to be safe with no findings of clinical
      significant changes during the study.

PMID- 21722496
TI  - Presence of eggs of Toxocara spp. and hookworms in a student environment in Rio
      Grande do Sul, Brazil.
AB  - Environmental contamination by parasite forms was studied on a university campus
      in the municipality of Pelotas, Rio Grande do Sul. Soil samples were analyzed
      using the modified Caldwell & Caldwell technique to identify parasite forms.
      Nematode eggs were detected in 62% of the samples. Among the parasites detected,
      eggs of Toxocara spp. and Ancylostomatidae were the most prevalent parasites in
      the studied area throughout the study period. The results demonstrated that there
      is significant environmental contamination, thereby representing a risk of
      zoonotic infection for humans frequenting the study area.

PMID- 21722497
TI  - Parasitism rates of Lipoptena guimaraesi and a new record of Lipoptena mazamae on
      Ozotoceros bezoarticus from the Central Pantanal wetlands in Brazil.
AB  - From May to October of 2006 we collected 143 louse flies of the genus Lipoptena
      on the body surface of 16 pampas deer Ozotocerus bezoarticus captured in four
      farms from the central area of the Brazilian Pantanal wetlands. We also examined
      172 cattle individuals and none of them had louse flies. Most of the parasites
      identified were Lipoptena guimaraesi but one specimen of L. mazamae was also
      found, representing a new host record for this ked fly. The prevalence of L.
      guimaraesi was 93.8%, the mean intensity of infestation was 9.5, and the index of
      discrepancy was 0.444.

PMID- 21722498
TI  - Ultrasound imaging for the rheumatologist XXXIII. Sonographic assessment of the
      foot in early arthritis patients.
AB  - OBJECTIVES: To investigate the ability of ultrasonography (US) to detect
      synovitis in metatarsophalangeal joints (MTP) in patients with suspicion of early
      arthritis, and to discriminate between diagnoses. METHODS: Patients referred to
      early arthritis clinics for differential diagnosis were enrolled, and clinical
      and laboratory measures were recorded. Ultrasonography of MTPs was performed
      searching for synovial hypertrophy (SH), joint effusion (JE) and power Doppler
      (PD), graded from 0 to 3 on a semi-quantitative scale. Patients were classified
      according to definite classification criteria, or as undifferentiated arthritis
      or non-inflammatory pathology. US findings were compared across different
      diagnoses and diagnostic accuracy was calculated taking clinical diagnosis as
      reference. RESULTS: Out of 427 patients (71% rheumatoid arthritis (RA), 20%
      undifferentiated arthritis (UA), 15% spondyloarthritides (SpA), 13% non
      inflammatory), 307 (71.9%) showed SH, 120 (25.5%) JE, 77 (18.0%) PD. RA patients
      had median JE, SH and PD scores significantly higher than non-inflammatory and
      other diseases. Patient with UA and SpA had higher scores of SH and JE compared
      to non-inflammatory, no significant differences were present among different
      diagnosis. In RA, SH and JE were more frequently detected in the second MTP, and
      PD in the fifth. Crystal-related arthritis showed a tendency towards a more
      frequent involvement of the first MTP. The diagnostic accuracy of single US
      measures was moderate, but the detection of a PD of 2 or more provided a high
      specificity for the diagnosis of RA. CONCLUSIONS: US can be used as additional
      information in patients evaluated in an early arthritis setting. High scores of
      JE, SH and PD, together with the pattern of involvement are suggestive of RA.

PMID- 21722499
TI  - Greater remission rates in patients with early versus long-standing disease in
      biologic-naive rheumatoid arthritis patients treated with abatacept: a post hoc
      analysis of randomized clinical trial data.
AB  - OBJECTIVES: Current aim of rheumatoid arthritis (RA) treatment is to achieve
      remission in as many patients as possible. Rates of remission and clinical
      outcomes after treatment with abatacept in biologic-naive rheumatoid arthritis
      (RA) patients with early disease and an inadequate response to methotrexate (MTX)
      versus patients with >= 10 years of disease were assessed. METHODS: Data from two
      trials assessing the efficacy of abatacept in MTX inadequate responders were
      pooled for this exploratory post hoc analysis. Patients with disease duration of
      <= 2 years at baseline (early disease), originally assigned to an abatacept
      approximately 10 mg/kg treatment arm and entered into a long-term extension
      (LTE), were compared with patients with >= 10 years of disease (long-standing
      RA). Remission, DAS28-CRP, ACR 70 responses and the Routine Assessment of Patient
      Index Data 3 (RAPID3), improvement in physical function as measured by the Health
      Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Twenty-three percent
      of these patients (n=108) had early disease. A higher percentage of patients with
      early disease achieved DAS28-CRP remission versus patients with long-standing
      disease (35.2% vs. 19.4% at year 1, p<0.01; 46.0% vs. 30.9% at year 3, p<0.05).
      In addition, a higher percentage of the subgroup with early RA achieved ACR70
      responses. More patients with early RA had a meaningful improvement in their HAQ
      DI (75.2% vs. 60.4%; p<0.05) and RAPID3 scores at one year (mean changes from
      baseline of -9.6 vs. -8.1; p=0.009). CONCLUSIONS: These data provide additional
      support for the possible use of abatacept in biologic-naive patients who have had
      inadequate response to MTX, earlier in their disease course.

PMID- 21722500
TI  - Imaging of tophi with an extremity-dedicated MRI system.
AB  - OBJECTIVES: To describe the MRI features of gout tophi in the soft-tissues or
      joints of the limbs by low-field extremity-dedicated MRI. METHODS: Nine
      consecutive patients, 8M/1W, affected by chronic tophaceous gout were studied.
      Mean patients' age was 71.3+/-11.5 years, mean disease duration 98.1+/-44.9
      months, and mean serum uric acid concentration 9.2+/-2.8 mg/L. Diagnosis was
      based on the ACR classification criteria for gout, and by identification of MSU
      crystals in the tophi and synovial fluid. Conventional radiograms and MRI with an
      extremity-dedicated system were obtained of the joint areas involved by tophi.
      RESULTS: At T1 weighted MRI images, all tophi showed a homogeneous intermediate
      signal intensity, similar to that of muscle. Conversely, in T2 weighted images, a
      wide spectrum of signal intensity patterns was observed. The pattern of contrast
      enhancement was variable from intense homogeneous to peripheral and
      heterogeneous. Capsulo-ligamentous structures were often thickened and
      degenerated and, on occasion, could be recognised as inhomogeneous, hypointense
      ribbon-shaped elements in the context of the tophus. In only two cases, tendons
      were infiltrated by tophaceous matter. Bone marrow oedema (BME) and erosions were
      seen in 8 out of 10 bones adjacent to tophi. CONCLUSIONS: The MRI appearance of
      gout tophi using an extremity-dedicated machine is similar to that described in
      the literature using whole body machines. BME adjacent to the tophus was a
      frequent finding. This technique may occasionally help in the differential
      diagnosis of nodules and in the follow-up of the disease. It also represents a
      useful tool to investigate the pathogenesis of gout and to better understand its
      clinical progression.

PMID- 21722501
TI  - Comparative efficacy and safety of two different molecular weight (MW)
      hyaluronans F60027 and Hylan G-F20 in symptomatic osteoarthritis of the knee
      (KOA). Results of a non inferiority, prospective, randomized, controlled trial.
AB  - OBJECTIVES: To compare the efficacy and safety of a 'medium' molecular weight
      (MW) hyaluronan product (F60027, Structovial) with a 'high' MW (Hylan G-F20,
      Synvisc). METHODS: Prospective, randomised, multicentre, double-blind, active
      controlled, parallel-group study with a non-inferiority design. Patients with
      symptomatic KOA, global pain >= 40 mm (VAS, 0-100), Lequesne index (LFI, 0-24)
      score >7 and radiological Kellgren-Lawrence grade 2/3 were centrally randomised
      to receive F60027 or Hylan G-F20, administered via three weekly injections, with
      regular follow-up evaluations up to week 24 (W24). The primary outcome was LFI
      score change over 24 weeks. Secondary outcomes comprised pain VAS, quality of
      life, patient's and physician's global assessments, rescue medication consumption
      and OMERACT-OARSI responders rate. RESULTS: 276 patients were analysed in the
      full analysis dataset (FAS), 236 in the Per Protocol dataset (PP). In the main
      efficacy analysis (PP), the difference of the LFI score change over 24 weeks
      between F60027 (-4.67 (0.27)) and Hylan G-F20 (-4.54 (0.28)) was 0.132 [95%CI: 
      0.598, 0.861] which met the predefined non-inferiority margin. Analyses of
      secondary efficacy criteria showed clinically relevant improvements of all
      outcomes at W24 for each treatment on both PP/FAS populations. Changes of LFI
      score between baseline and W24 were -5.73 in the F60027 and -5.57 in the Hylan G
      F20 group (PP dataset). Few local reactions were reported: 3.6% of patients in
      each group. CONCLUSIONS: F60027 and Hylan G-F20 were equally effective in
      reducing functional impairment and relieving pain in KOA patients, and well
      tolerated.

PMID- 21722502
TI  - Histological changes in chronic autoimmune SKG-arthritis evaluated by
      quantitative three-dimensional stereological estimators.
AB  - OBJECTIVES: To investigate the quantitative arthritic and bone erosive changes,
      including the number of osteoclasts and osteoclast precursors in the new SKG
      model of inflammatory polyarthritis using three-dimensional (3D) stereological
      methods. METHODS: Arthritis was induced in female SKG-mice with Zymosan A.
      Quantitative histology was made in four control mice and four mice with arthritis
      euthanised after 6 and 12 weeks. The right hind paw was embedded undecalcified in
      methylmethacrylate and cut exhaustively generating vertical uniform random
      sections. A computer controlled microscope and stereological software was used
      for histological quantification. Total volumes were estimated according to the
      Cavalieri principle, total surfaces were estimated using the vertical sections
      design, and the number of osteoclasts was counted in a physical fractionator.
      RESULTS: The arthritis score increased during the 12-week period and was
      paralleled by an increase in the volume of inflammatory tissue (r=0.96, p<0.001).
      The number of osteoclasts on bone (r=0.77, p<0.05) and osteoclast-covered bone
      surface (r=0.62, p<0.05) increased resulting in a decrease in the volume of bone
      (r=-0.65, p<0.05). However, the number of osteoclast precursors declined between
      week 6 and 12 (p<0.05). Furthermore, the total cartilage surface (r=-0.74,
      p<0.05) and cartilage volume (r=-0.74, p<0.05) decreased during the 12 weeks of
      arthritis. CONCLUSIONS: In this study we demonstrated changes in 3D stereological
      parameters of inflammatory tissue, bone erosion, osteoclasts, and cartilage in
      mouse paws during the course of arthritis in the SKG mouse. This is the first
      time 3D quantitative histology has been applied in a mouse model of rheumatoid
      arthritis.

PMID- 21722503
TI  - Patients with systemic lupus erythematosus (SLE) having developed malignant
      lymphomas. Complete remission of lymphoma following high-dose chemotherapy, but
      not of SLE.
AB  - The development of malignant lymphomas, generally of the non-Hodgkin type (NHL),
      and with a preference to diffuse large cell B lymphomas (DLCBL), in systemic
      lupus erythematosus (SLE), has been analysed in an exhaustive recent literature.
      The combination of germline and somatic mutations, persistent immune
      overstimulation and the impairment of immune surveillance facilitated by
      immunosuppressive drugs, is thought to be at the origin of the increased lymphoma
      genesis. However the treatment and course of such affected patients is less
      known, and prognosis is generally estimated as poor. Out of 258 patients with
      complete/incomplete lupus and secondary antiphospholipid syndrome (APS) seen and
      treated at the institutional Day Hospital between 1982 and 2009, 6 developed
      lymphomas (4 DLCBL, 1 Hodgkin's and 1 indolent lymphocytic lymphoma). The first 5
      patients were treated with high dose chemotherapy (HDCT) and achieved complete
      remissions (CR) with a follow-up comprised between 13 and 172 months. One patient
      relapsed of lymphoma and died 15 months following CR, with persistent lupus
      serology. One patient achieved complete remission (CR) of both diseases. In the
      other 3 lupus serology, Antinuclear and antiphospholipid antibodies (ANA, aPL)
      persisted, with occasional lupus flares and vascular complications. While
      eradication of the last cancer stem cell is tantamount to cure in neoplastic
      disease, persistent autoantigenic overstimulation may contribute to the
      refractoriness of autoimmunity. The implications of these results for the
      increasing utilisation of haematopoietic stem cell transplantation for severe
      autoimmune diseases (SADS), with lupus as a paradigm, are discussed.

PMID- 21722504
TI  - Difficulties for the detection of positive signs of sacroiliitis in
      spondyloarthritides by magnetic resonance imaging (MRI) in everyday clinical
      practice. Results from an audit circle (audit and re-audit).

PMID- 21722505
TI  - A cross-sectional audit of the uptake of seasonal and H1N1 influenza vaccination
      amongst patients with rheumatoid arthritis in a London hospital.

PMID- 21722506
TI  - Chronic fatigue syndrome is commonly diagnosed in patients with Ehlers-Danlos
      syndrome hypermobility type/joint hypermobility syndrome.

PMID- 21722507
TI  - Association between anti-dsDNA titre increase and thymoma relapse.

PMID- 21722508
TI  - [Diabetes type 1 therapy individualization among children suffering from autism
      spectrum disorder].
AB  - Over the last years studies suggest an association between type 1 diabetes (DM1)
      and autism spectrum disorder (ASD). In this case study two children suffering
      from DM 1 and ASD were presented. Both are treated in the Centrum Zdrowia Dziecka
      in Katowice, Poland. The authors highligh everyday problems and challenges that
      patients, tutors and doctors have to face. The key to effective treatment is its
      individualization connected with proper education of the patient and his
      caregivers.

PMID- 21722509
TI  - Non-coding glucometers among pediatric patients with diabetes: looking for the
      target population and an accuracy evaluation of no-coding personal glucometer.
AB  - INTRODUCTION: Self-monitoring of blood glucose (SMBG) is one of the cornerstones
      of diabetes management. AIM OF THE STUDY: To evaluate the potential for miscoding
      of a personal glucometer, to define a target population among pediatric patients
      with diabetes for a non-coding glucometer and the accuracy of the Contour TS non
      coding system. MATERIAL AND METHODS: Potential for miscoding during self
      monitoring of blood glucose was evaluated by means of an anonymous questionnaire,
      with worst and best case scenarios evaluated depending on the responses pattern.
      Testing of the Contour TS system was performed according to guidelines set by the
      national committee for clinical laboratory standards. RESULTS: Estimated
      frequency of individuals prone to non-coding ranged from 68.21% (95% 60.70-
      75.72%) to 7.95% (95%CI 3.86-12.31%) for the worse and best case scenarios
      respectively. Factors associated with increased likelihood of non-coding were: a
      smaller number of tests per day, a greater number of individuals involved in
      testing and self-testing by the patient with diabetes. The Contour TS device
      showed intra- and inter-assay accuracy -95%, linear association with laboratory
      measurements (R2=0.99, p <0.0001) and consistent, but small bias of -1.12% (95%
      Confidence Interval -3.27 to 1.02%). Clarke error grid analysis showed 4% of
      values within the benign error zone (B) with the other measurements yielding an
      acceptably accurate result (zone A). CONCLUSIONS: The Contour TS system showed
      sufficient accuracy to be safely used in monitoring of pediatric diabetic
      patients. Patients from families with a high throughput of test-strips or
      multiple individuals involved in SMBG using the same meter are candidates for
      clinical use of such devices due to an increased risk of calibration errors.

PMID- 21722510
TI  - [Generation of T regulatory cells in children with type 1 diabetes mellitus].
AB  - INTRODUCTION: In spite of intensive research the pathogenesis of type 1 diabetes
      mellitus is not thoroughly understood. One of the ideas which currently has a
      great number of supporters is the theory of the participation of T regulatory
      cells in the mechanism of insufficient suppression of the immune response against
      pancreatic self -antigens. According to some authors, the infusion of T
      regulatory cells in autoimmune diseases could lead to long -term remission or
      even a complete cure. AIM OF THE STUDY: The aim of our present study was to
      achieve T regulatory cells from conventional T lymphocytes isolated from a small
      amount of peripheral blood in children with type 1 diabetes mellitus and their
      comparison to the Tregs generated from the blood of control children.
      Additionally, we assessed the changes in the expression of selected genes
      essential for the function of these cells during Tregs generation. MATERIAL AND
      METHODS: The examined group consisted of 20 children with type 1 diabetes
      mellitus, the control group consisted of 20 non -diabetic children. From the
      peripheral blood CD4+CD25 - cells were separated and cultured with T -reg
      expander and interleukin (IL) 2. Before and after the culture the cells were
      analysed according to the expression of transcription factor FoxP3 and other
      molecules/cytokines: OX40, 4 -1BB, GITR, ICOS -1, CTLA -4 and IFN -gamma, IL -10
      and TGF -beta. RESULTS: We observed a significantly higher percentage of T
      regulatory cells after the culture (with no difference between diabetic and
      control children). Moreover, we observed a lower expression of mRNA for GITR
      molecule and a higher IL -10 expression in the cultures of diabetic children
      compared to the control ones. The cells cultured from the blood of control
      children were characterised by a higher increase in the expression of mRNA for
      ICOS -1 and a lower expression of mRNA for TGF -beta in comparison to the
      cultures from diabetic children. CONCLUSIONS: The results of our investigations
      confirm the possibility of generating T regulatory cells from conventional T
      lymphocytes from peripheral blood of children with newly recognised type 1
      diabetes mellitus.

PMID- 21722511
TI  - High prevalence of spirometric abnormalities in patients with type 1 diabetes
      mellitus.
AB  - INTRODUCTION AND AIM OF THE STUDY: To document abnormalities on spirometry in
      patients with type1 diabetes mellitus (DM) and to study the determinants of
      these. MATERIAL AND METHODS: Thirty nine patients attending the type 1 DM clinic
      underwent spirometry. The absolute FEV1 and FVC were compared with the predicted
      ones and expressed as a percentage of the predicted. Additional information
      collected included gender, age, weight, height and the latest glycated
      hemoglobin. Data were presented as mean+/-SD.chi2 test was used to study
      differences in proportions and Pearson's coefficient was calculated for
      correlations. RESULTS: Twenty patients (51.2%) had pulmonary function
      abnormalities, of which 17 patients had a restrictive pattern on spirometry and 3
      had an obstructive pattern. Of all the patients, 45.8% were stunted, i.e. had the
      height SDS <-2 SD while 25.7% were extremely stunted (height SDS < -3). Sevenof 9
      (77.8%) patients with extreme stunting (Ht SDS <-3) had restrictive ventilatory
      disturbances, whereas only 8 of 26 (30.7%) persons with Ht SDS above -3 had the
      same (p <0.05). CONCLUSIONS: Spirometric abnormalities are common in type 1 DM
      and stunting is a significant determinant of the same.

PMID- 21722512
TI  - [Nutritional behaviours of pregnant women].
AB  - INTRODUCTION: Errors in nourishment and unstable nutritional status of pregnant
      women can have a negative impact on the development of the foetus and the course
      of pregnancy. THE AIM OF THE STUDY: THE AIM OF THE STUDY was the estimation of
      nutritional behaviour of pregnant women, nutritional status before pregnancy and
      their body weight gain during pregnancy. It is also examined whether the
      educational level is a factor that differentiates the manner of nourishment, and
      the nutritional status of the investigated women. MATERIAL AND METHODS: The
      investigation included 200 women, 30 of them were in I, 70 - in II, and 100 - in
      III trimester of pregnancy; 19% had elementary general or vocational education;
      35% - secondary education; and 46% - higher education. Information about eating
      habits as well as body height and mass was collected by means of an anonymous
      questionnaire. BMI of the investigated women before pregnancy and average weekly
      increases of body mass during pregnancy were calculated. RESULTS: The
      investigation has shown insufficient consumption of vegetables and fruits, milk
      and dairy products, wholemeal cereal products, fish or supplements containing
      polyunsaturated fatty acids n-3, and high consumption of sweets. The folic acid
      before or during pregnancy was taken by 88% of the investigated women. An
      insufficient body mass before pregnancy (BMI <18.5) was found in 7%, and a small
      body weight gain during pregnancy was found in 28.8% of women. 5% of the
      investigated women had both risk factors simultaneously. CONCLUSIONS: A number of
      irregular nutritional behaviours were found among the investigated women. Most
      errors in nourishment were found in the group of women with elementary general or
      vocational education.

PMID- 21722513
TI  - [The vitamin D and calcium consumption and bone quality in children of lodZ
      (Poland) at the age 9-13 years].
AB  - INTRODUCTION: Only few publications concern the influence of the vitamin D and
      calcium consumption on the bone mineralization in the developmental age. AIM OF
      THE STUDY: The aim of the study was the analysis of the vitamin D and calcium
      diet supply in relation to the bone status assessed with Quantitative Ultrasound
      (QUS) in growing children. MATERIAL AND METHODS: The study comprised 643 pupils
      (384 girls and 259 boys) at the age 9-13 years from primary schools in lodZ. The
      medium daily consumption of vitamin D and calcium was estimated with the computer
      program Dieta 2. In all children the QUS was performed. RESULTS: Extreme
      deficiency of vitamin D was found in the diet of nearly all examined children (in
      96,7% schoolgirls and 95,7% schoolboys). Girls consumed on average 25,5% of
      recommended values, boys 33,3%. Considerable deficiency of diet calcium was
      observed in 92% schoolgirls and 81,9% of schoolboys. The medium daily consumption
      of calcium was higher than vitamin D and reached 59,2% of recommended values in
      girls and 66,2% in boys. In 48% of children an decrease of at least one of the
      QUS parameters was observed. The statistical analysis showed positive,
      significant correlation between QUS parameters and calcium consumption, it was
      not observed for vitamin D. CONCLUSIONS: 1. The deficiency of diet vitamin D and
      calcium is common in children in lodZ. 2. The extremely low supply of diet
      vitamin D does not meet the recommended values. 3. The lowering of the QUS
      parameters observed in 48% of children indicates for worse bone mineralization
      and bone quality. 4. The results of this study indicate for the necessity of
      changes in nutritional habits of children and adolescence and if it is not
      possible the supplementation of vitamin D and calcium.

PMID- 21722514
TI  - [Physical fitness of short-statured girls in pubertal age].
AB  - INTRODUCTION: Objective evaluation of physical fitness during adolescence is of
      importance in a school practice. Low body height may decide of unequal chances of
      short-statured youth as compared to other pupils performing physical fitness
      test. AIM OF THE STUDY: To assess physical fitness of short-statured girls aged
      13-16. MATERIAL AND METHODS: 20 short-statured girls (body height below 10th
      percentile) from the province of Lodz aged 13-16 (15.1+/-0.9) years took part in
      the study. Their body height and body mass were 143.0+/-10.7 cm and 44.7+/-9.2
      kg, respectively. Physical fitness was assessed with the use of EUROFIT test
      battery. The results were standardised against the functions of means and
      standard deviations for age computed for the Polish population and compared with
      the t-test. RESULTS: As compared to girls from a general population, a short
      statured one performed significantly worse with respect to two tests: SAR (sit
      and-reach) and SBJ (standing board jump; p <0.01). In other fitness tests the
      results obtained were similar. It was also found that body height correlated
      positively and body mass negatively with general physical fitness. CONCLUSIONS:
      In order to compensate deficiencies in physical fitness of short-statured girls,
      particular attention should be paid to shaping those abilities in which they
      performed worse. On the other hand, changing the attitude towards evaluation in
      physical education should be also considered as to make it adequate to somatic
      possibilities of short-statured pupils and thus motivate them to undertake
      physical activity.

PMID- 21722515
TI  - Body image of tall and medium girls aged 13-17 years.
AB  - INTRODUCTION: Adolescent girls often experience difficulties in a rational
      perception of own body and consider attaining an "appropriate shape" as a key to
      success and happiness. Growth disorders, like e.g. very tall stature, may bring
      about stigmatising which, in turn, may decrease in such girls their self-esteem,
      especially in adolescence. Aim of the study was to assess the perceived body
      image of tall and medium-statured girls and to compare their self-rating with an
      external one. MATERIAL AND METHODS: A group of 56 girls aged 13-17 years were
      classified into two categories of body height: medium stature, between
      Percentiles 40 and 60 (n=36) and tall, above Percentile 90 (n=20). Using a
      template containing 9 female body shapes, the girls indicated the shape they
      thought they had, the shape they wished to have, and an external rating was also
      made. Girls rated as shapes 1 or 2 were classified as thin, shapes 3 or 4 as
      medium and shape 5 or higher as robust. The data were related to the BMI values.
      RESULTS: Thin girls self-rated their body shapes and the desired ones
      significantly higher (p <0.05) compared with the external rating. In medium
      shaped girls the same was true for self-rating, the desired shape being
      concordant with the external rating. In robust girls, the external and self
      ratings were concordant, the desired shapes being significantly lower (p <0.05)
      but higher (p <0.05) in tall than in medium-height girls (5.0 and 3.9,
      respectively). Tall and medium girls did not differ significantly in BMI but a
      very high correlation (r=0.930; p <0.001) was found between the externally rated
      body shape and BMI in both groups of girls. CONCLUSION: The distorted perception
      of own body shape by adolescent girls may result from the specific ideals of
      feminine beauty and excessively slim silhouette insistently promoted by mass
      media and fashion designers. Popularisation of the results of this and similar
      studies may contribute to altering the respective attitudes of adolescent girls.

PMID- 21722516
TI  - [Evaluation of physical development of children with congenital hypothyroidism
      detected in the screening test--personal observations].
AB  - INTRODUCTION: Congenital hypothyroidism (CH) is the most prevalent endocrinopathy
      resulting from thyroid hormones deficiency or lack of thyroid hormones (TH). Aim
      of the study is to evaluate the physical development of children with congenital
      hypothyroidism detected in screening tests, determine the effect of TSH level,
      thyroid hormones and perinatal, parental and environmental factors on the
      physical development of children. MATERIAL AND METHOD: the study involved 79
      children (47 girls, 32 boys) aged 3-18 years (mean age 7.3+/-3.5) with CH
      diagnosed in screening tests. Children's development was analysed in correlation
      with TSH value in the screening test, time of commencement of therapy with LT4,
      the initial dose of the LT4, mean TSH level in the first year of life, mean value
      of TSH and LT4 in the 2-year follow-up period, social origin, place of residence
      (village, city), parents': anthropometric parameters (BMI, height), age, level of
      education of the parents, which pregnancy it was, time of pregnancy. In children:
      body mass and length at birth, score on Apgar scale, additional chronic disease.
      RESULTS: Too low body mass was usually observed in the 2-4 month of life - 11.1%,
      while in the following months, the number of children with body mass below the 3
      centile became lower. In children diagnosed with too low body mass <18 month of
      life, in the subsequent months was observed a normalisation. No correlation was
      between the body mass and TSH in infancy, the place of residence and level of
      education of the parents in all examined groups. According to Palczewska, BMI >97
      centile occurred more often in the group of children with CH in the age range of
      11 months - 6.9 years than in the control group, whereas >=7 years obesity did
      not occur. The number of children with insufficient body length increased in the
      age groups: 11-18 months - 7.4%; 1.6-3.9 years - 7.9 % and 4-6.9 years - 9.1%.
      Children >=7 years with height <3 centile were not observed. The number of
      children with height >97 centile in three age groups did not go beyond 4%. The
      biggest number of children >97 centile was noted in the age group 1.6-3.9 years
      (7.9%). Mean height SDS in all age groups was within the norm (+/-1 SDS for
      healthy population). CONCLUSIONS: 1. Physical development of children in infancy
      was in normal range. 2. Mean SDS of body mass in children was in the range of
      1sds for healthy population in each age quarter. 3. Mean SDS for BMI in all age
      groups was above zero. 4. Mean SDS for body length in all age groups was in the
      range +/-1 SDS for healthy population. 5. Early initiation of therapy HT is a
      prerequisite for proper physical development of children with congenital
      hypothyroidism.

PMID- 21722517
TI  - [Polymorphisms of lipoprotein lipase gene and their participation in metabolic
      processes].
AB  - Lipoprotein lipase (LPL) plays a central role in dyslipidemia and development of
      metabolic syndrome. The occurrence of polymorphisms of the LPL gene may result in
      the disturbance in the lipid metabolism and pathogenesis of CAD. Carriers of X447
      allele were reported to have lower triglyceride and higher high-density
      lipoprotein cholesterol levels as well as a reduced risk of CAD. The patiens with
      hypertriglicerydemia are carriers of common PLP mutations as Asp9Asn,Asn291Ser,
      Trp86Arg, Gly188Glu, Pro207Leu, and Asp250Asn. LPL is an interesting enzyme that
      contributes in a pronounced way to normal metabolism, including insulin action,
      body weight regulation, energy balance, and atherosclerosis. In this rewiev, the
      roles of polymorphism LPL and their implications in the control of lipoprotein
      metabolism and atherosclerosis are discussed, especially in the group of risk
      developing metabolic syndrome - children with low birth weight (below 2500 g).

PMID- 21722518
TI  - [Construction of recombinant adenovirus of SEA and CD80 genes co-expression
      regulated by mouse TERT promoter and identification of its expression in hepatoma
      cells].
AB  - AIM: To construct recombinant co-expression adenovirus vector of SEA and CD80
      genes regulated by mouse TERT(telomerase reverse transcriptase, TERT) promoter
      and to observe the expression of SEA and CD80 in the Hepa1-6 cells mediated by
      it. METHODS: Using AdEasy adenovirus system, the core promoter region of mTERT
      was subcloned to shuttle plasmid pShuttle2 and Myc-Max response element was
      inserted upstream of it to regulate the expression of SEA and CD80. The
      recombinant co-expression adenovirus vector of SEA and CD80 genes was constructed
      and named as Ad-MMRE-mTERT-BIS. Hepatoma cell line Hepa1-6 and fibroblast cell
      line NIH3T3 were infected by recombinant adenovirus at MOI(multiplicity of
      infection)of 100, the expression of SEA and CD80 on the surface of cells was
      detected by indirect immunofluorescent staining. RESULTS: SEA and CD80 was
      specifically co-expressed on the surface of infected Hepa1-6 cells but not on
      NIH3T3 cells. CONCLUSION: The recombinant co-expression adenovirus vector of SEA
      and CD80 gene regulated by mTERT promoter was sucessfully constructed and make
      targeting-expression of SEA and CD80 on the surface of hepatoma cells, which lays
      the foundation for further research on application of SEA and CD80 in targeted
      genetherapy for hepatoma.

PMID- 21722519
TI  - [Construction of lentiviral expression vector containing Foxp3 gene and its
      expression in DC2.4 cell line].
AB  - AIM: To construct a Foxp3 lentiviral vector and transfer it into DC2.4 cells,
      which provides Foxp3+DC cells for further study on its immune modulation.
      METHODS: We cloned mouse Foxp3 gene into lentiviral vector(pGC-FU) and acquired
      the plasmid pGC-FU-Foxp3. PCR and sequencing analysis were made for verifying the
      positive clones. The virus packaging plasmids(pGC-FU-Foxp3, pHelper1.0 and
      pHelper2.0) were contransfected into 293T cells, and the Lentivirus-Foxp3 was
      harvested from 293T cells. The Lentivirus-Foxp3 was used to infect DC2.4 cells in
      vitro and the expression of Foxp3 in infected DC2.4 cells was detected with flow
      cytometry(FCM). RESULTS: PCR and sequencing revealed that the pGC-FU-Foxp3
      plasmid was correctly constructed. The Lentivirus-Foxp3 with a titer of 2*10(8);
      TU/mL was successfully packaged. Foxp3 expression in DC2.4 cells infected with
      the Lentivirus-Foxp3 was increased significantly compared with negative control
      lentivirus. CONCLUSION: The pGC-FU-Foxp3 plasmid has been successfully
      constructed and the Lentivirus-Foxp3 has been successfully packaged. Foxp3 can be
      enhanced in DC cells infected with the Lentivirus-Foxp3.

PMID- 21722520
TI  - [Effects of andrographolide on the concentration of cytokines in BALF and the
      expressions of type I and III collagen mRNA in lung tissue in bleomycin-induced
      rat pulmonary fibrosis].
AB  - AIM: To investigate the effects of andrographolide on the concentration of TNF
      alpha and TGF-beta1 in bronchoalveolar lavage fluid (BALF) and the expressions of
      type I and III collagen mRNA in Lung tissue in bleomycin (BLM)-induced pulmonary
      fibrosis in rats. METHODS: 90 healthy SD male rats were randomly divided into 6
      groups with 15 rats each group: normal saline (NS) group, BLM group, prednisone
      (Pred) group and different doses of andrographolide groups (andrographolide group
      A 62.5 mg/kg, andrographolide group B 125 mg/kg and andrographolide group C 250
      mg/kg). BLM was given to BLM group, Pred group and andrographolide group A, B, C
      by intratracheal instillation, and same volume of NS was given to NS group in the
      same way. And then NS was given to NS group and BLM group, Pred was given to Pred
      group and different does of andrographolide were given to andrograoholide group
      A, B, C by gavage every day. Five rats of each group were killed respectively at
      day 7, 14, 28 after intratracheal instillation. Alveolitis and fibrosis were
      observed by HE and Masson staining. Real-time fluorescent quantitative reverse
      transcription- polymerase chain reaction (FQ RT-PCR) was performed to detect the
      expressions of type I and III collagen mRNA in lung tissue, and the concentration
      of TNF-alpha and TGF-beta1 in BALF was determined by enzyme-linked immunosorbnent
      assay. Blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) were also examined. RESULTS: (1) The AST,
      ALT, BUN and Cr in every group had no significant diference(P>0.05). (2) Alveolar
      septal edema, inflammatory cell infiltration and fibrosis were not found in NS
      group. In the BLM group, lots of inflammatory cells infiltration were observed in
      the alveolar at day 7; the alveolitis was still existed, but inflammatory cells
      were significantly reduced, and the number of the fibroblasts and matrix in
      alveolar septum were obviously increased at day 14, at the same time, alveolar
      structure was damaged and alveolar septum widened; the inflammation cells
      infiltration of the alveolar was relieved, pulmonary fibrosis was increased, and
      parts of alveolar space was disappeared , severe fibrosis was found at day 28. It
      was similar between andrographolide group A and BLM group in pathomorphology. A
      lot of inflammatory cells infiltration and local accumulation were observed at
      day 7 in andrographolide group B, C and Pred group. However, compared with
      andrographolide group A and BLM group, the fibrosis at day 14, 28 was
      significantly reduced.(3) The concentration of TGF-beta1, TNF-alpha in BALF of NS
      group was significantly lower than that of Pred group, BLM group, andrographolide
      group A, B, C at each time point(P<0.05). The concentration of TGF-beta1 and TNF
      alpha in BALF of BLM group at day 7, 14, 28 was higher than that of Pred group,
      andrographolide group B and andrographolide group C (P<0.05). Compared with BLM
      group, the concentration of TGF-beta1 and TNF-alpha in BALF of andrographolide
      group A had no significant difference. (4) The expression of type I and III
      collagen mRNA in lung tissue of NS group was significantly lower than that of
      group Pred, BLM, andrographolide group A, B, C at each time point (P<0.05). The
      expression of type I and III collagen mRNA in lung tissue of BLM group at day 7,
      14, 28 was higher than that of Pred group, andrographolide group B and
      andrographolide group C (P<0.05). Compared with BLM group, the expression of type
      I and III collagen mRNA in lung tissue of andrographolide group A had no
      significant difference. CONCLUSION: In BLM-induced rat pulmonary fibrosis,
      andrographolide could attenuate alveolitis and fibrosis, decrease mRNA expression
      of collagen I and III in lung tissue and decrease the concentration of TNF-alpha
      and TGF-beta1 in BALF. It had no side effects on liver and kidney function.

PMID- 21722521
TI  - [Effects of CD74 gene on IFNgammaR gene expression in MG TEC].
AB  - AIM: To study the effects of CD74 gene on IFN-gammaR expression in myasthenia
      gravis thymic epithelial cell(TEC). METHODS: PCMV-CD74 transiently transfect to
      primary cultured TEC mediated with lipofectamine, the result of transfection and
      some autoimmune related genes such as IFN-gammaR were detected by real-time RT
      PCR. RESULTS: Real-time quantitative RT-PCR results show that the mRNA expression
      level of IL-4R, IL-32, IFN-gammaR, ECGF1, HLA-A, HLA-DR increased significantly,
      with the high express ion of CD74 gene in thymic epithelial cells. CONCLUSION:
      CD74 gene over-expression in TEC can increase IFN-gammaR mRNA expression.

PMID- 21722522
TI  - [Effect of tanshinone II A on TLR4 and TNF-alpha of endothelial cells induced by
      LPS].
AB  - AIM: To observe the influence of tanshinone II A on the expression of toll like
      receptor 4(TLR4) and tumor necrosis factor-alpha(TNF-alpha) in cultured human
      umbilical veins endothelial cells EA.hy926 induced by LPS, and to investigate the
      molecular mechanism of tanshinone II A against atherosclerosis(AS). METHODS: The
      EA.hy926 cells were cultured in vitro. The mRNA and protein expression of TLR4
      were tested by RT-PCR and immunocytochemistry technique respectively. The mRNA
      and protein expression of TNF-alpha were detected by RT-PCR and ELISA technique
      respectively. RESULTS: The expression of TLR4 and TNF-alpha were both increased
      compared to normal group after stimulation of LPS(P<0.05). The expression of TLR4
      and TNF-alpha in tanshinone II A group were obviously inhibited compared to
      stimulation group(P<0.05). CONCLUSION: The molecular mechanism of tanshinone II A
      against AS is probably to inhibit the expression of TLR4 and TNF-alpha.

PMID- 21722523
TI  - [The effect of serum concentration on the growth, proliferation and collagen
      secretion in mouse L929 fibroblasts].
AB  - AIM: To observe the effect of serum concentration on the growth, proliferation
      and secretion of collagen I, collagen III and hydroxyproline in mouse fibroblasts
      L929, to optimize serum concentration for cell growth, proliferation and collagen
      secretion. METHODS: L929 cells were divided into 6 groups cultured in the present
      of 0 mL/L, 200 mL/L, 400 mL/L, 600 mL/L, 800 mL/L and 1 000 mL/L serum
      respectively. Acridine Orange and HE staining were performed on 2 d, 4 d, 6 d and
      8d and sulforhodamine B sulfonyl chloride was used to determine cell
      proliferation at the same time; Meanwhile, the supernatants of each group ware
      collected and enzyme immunoassay was performed to detect the protein levels of
      collagen I, III and hydroxyproline. RESULTS: (1) The cell proliferation was
      inhibited when serum concentration was very high (100%) or very low (0%). The
      proliferation rate in the presence of 20% serum was the highest. When serum
      concentration was higher than 20%( 40%-100%), the cell proliferation decreased.
      (2) Apoptotic cells were observed in the absence of serum. Vacuolization appeared
      in the presence of 80% serum, and was enhanced in the case of 100% serum. Cells
      were morphologically normal when serum concentrations were between 20%-60%.
      (3)The level of collagen I was low in the case of serum concentrations of 0%, 80%
      and 100%, with the highest expression in 40% serum. Collagen III in all groups
      was increased on day 2, followed by a transient decreased and an final increased
      on day 6-8. The level of hydroxyproline was not changed in all groups.
      CONCLUSION: The serum concentrations between 20%-40% is suitable for L929cells
      growth, proliferation and secret collagen. The extremes serum concentration of
      too high or too low leads to inhibition of cell proliferation, apoptosis,
      vacuolization, and impaired secretion of collagens. This study indicates the
      requirement of optimum serum concentration for self serum injection therapy.

PMID- 21722524
TI  - [The construction of NUDC shRNA interference vector with red fluorescence
      protein].
AB  - AIM: Used RFP gene to construct a RNA interference vector for convenience to
      obtain the good effective hairpins sequence. METHODS: NUDC and RFP genes were
      cloned into pDs vector separately, resulting in pDs-NUDC- RFP. as above, human U6
      promoter and 9 hairpins sequence of NUDC were cloned into the pDs- NUDC-RFP
      vector separately.The RNA interfererence vectors target to 9 points of NUDC were
      constructed. Construct- ed recombinant vectors and then were identified by
      restrictive digestion and DNA sequencing.293T cells were transfected with the
      recombinant DNA samples by the liposome complex method, and then fluorescence
      photographs were taken. RESULTS: Enzyme digestion and DNA sequencing showed that
      the target gene and shRNA fragments were correctly inserted in pDs vector.
      fluorescence photographs showed that shNUDC-A is the best effective fragment.
      CONCLUSION: The NUDC gene targeted shRNA and its vector are successfully
      constructed.

PMID- 21722525
TI  - [High glucose induce the demethylation of CTGF promoter and gene expression].
AB  - AIM: To investigate the effects of high glucose and 5-aza-2'-deoxycytidine (5-aza
      dCyd), a selective DNA methyltransferase inhibitor, on CTGF expression and
      methylation levels in human glomerular mesangial cells (HMCs). METHODS: HMCs were
      treated with 5-aza-dCyd with different concentrations (0, 1, 2, 5, 10 MUmol/L)
      for 48 h and cell lysates were collected for genomic DNA, total RNA and total
      protein; HMCs were cultured in DMEM medium containing different concentrations of
      D-glucose (5 or 30 mmol/L) and cell lysates were collected at different time
      points (0, 24, 48, 72 h); methylation-specific PCR (MSP) analysis was used to
      analyze the methylation status of CTGF gene promoter, while RT-PC and western
      blot were used to evaluate the expression of CTGF mRNA and protein, respectively.
      RESULTS: In 5-aza-dCyd treated (48 h) HMCs, CTGF gene promoter was hemi
      methylated in 0, 1, 2, or 5 MUmol/L groups, and there was low expression of CTGF
      mRNA and protein with no statistical difference between groups (P>0.05). But its
      methylation was completely reversed after treated with 10 MUmol/L 5-aza-dCyd and
      the mRNA and protein levels of CTGF in 10 MUmol/L group were significantly
      increased compared to 0 MUmol/L group (P<0.01). In the 5 mmol/L D-glucose-treated
      group, the promoter of CTGF was semi-methylation at all time points, and the
      expression levels of CTGF mRNA and protein at different time point were all low
      with no significant difference (P>0.05). However, in the 30 mmol/L group, the
      semi-methylation of CTGF promoter were detected at 0 h, and it was reduced at 24
      h and completely reversed at 48 h. The expression levels of CTGF mRNA and protein
      at 24, 48, or 72 h in 30 mmol/L group were all significantly elevated compared to
      5 mmol/L group(P<0.01). CONCLUSION: Both high glucose and 5-aza-dCyd could induce
      the demethylation process of CTGF gene promoter and increase the expression of
      CTGF mRNA and protein, indicating that DNA methylation is involved in the
      regulation of CTGF gene expression in HMCs.

PMID- 21722526
TI  - [The influence of rapamycin on BTLA expression of human peripheral blood T
      lymphocytes].
AB  - AIM: To explore the effect of rapamycin (RPM) on the expression of B and T
      lymphocyte attenuate (BTLA) on human peripheral blood T lymphocytes, providing a
      experimental basis for application of RPM to organ transplantation and autoimmune
      diseases. METHODS: Human peripheral blood mononuclear cells were isolated by
      Ficoll density gradient centrifugation, and then the T cells were isolated from
      PBMCs with immunomagnetic beads. Concanavalin A (Con A) used to stimulate and
      activate the human peripheral blood T cells. The proliferation of T cells was
      detected by MTT colorimetry. The levels of IL-2 and IFN-gamma in cell culture
      supernatant were detected by ELISA. The expression of BTLA on T cells was assayed
      by Flow cytometry. RESULTS: The expression of BTLA on T cells treated with
      various concentrations (10-1 000 ng/L) of RPM had no significant difference,
      while had significant difference (P<0.01) by compared with RPM non-treatment
      group. ELISA detection manifested that compared with the untreated group
      different concentrations of RPM could significantly inhibit the IL-2 and IFN
      gamma secretion and significantly inhibited T lymphocyte proliferation (P<0.01).
      CONCLUSION: RPM has little effect on expression BTLA, but has stronger inhibition
      on lymphocyte proliferation and inflammatory cytokines secretion. Suggesting that
      RPM is suitable for the treated of organ transplant rejection and autoimmune
      diseases.

PMID- 21722527
TI  - [Effect of estrogen on mismatch repair gene expression in colon cancer cells].
AB  - AIM: To investigate the effect of estrogen on MMR gene expression in colon cancer
      cells COLO205. METHODS: By employing semi-quantitative RT-PCR and Western
      blotting techniques, changes in the expression of MMR genes (hMLH1 and hMSH2)
      induced by different levels of estradiol (E2) and ICI182.780, an estrogen
      receptor inhibitor, was investigated in cultured COLO205 cells. The effect was
      then verified by real time RT-PCR. RESULTS: E2 enhanced the expression of hMLH1
      in COLO205 cells at transcriptional level, and a dose-response relationship was
      established when the concentration of E2 was between 10(-12);-10(-8); mol/L. The
      enhancement was suppressed by the estrogen receptor inhibitor ICI182.780. On the
      other hand, there was no significant effect of E2 on hMSH2 expression in COLO205
      cells. CONCLUSION: E2 can increase the expression of hMLH1 in colon cancer cells
      COLO205, and this finding sheds new light on the mechanism of estrogen protecting
      against colon cancer by regulating MMR system.

PMID- 21722528
TI  - [Expression, purification and activity assay of Streptococcus suis serotype 2
      cell wall protein SSU1664].
AB  - AIM: To amplify the SSU1664 gene from Streptococcus suis serotype 2 strain 05ZY,
      to express the gene in E.coli, and to evaluate the activities of the recombinant
      protein. METHODS: SSU1664 gene was amplified by PCR using primers according to
      05ZY genome sequences and cloned into the expression vector. The recombinant
      protein was purified by affinity chromatography and its immunogen activities were
      tested by Western blot and ELISA. RESULTS: SSU1664 gene could solublely express
      in E.coli BL21(DE3). Western blot analysis showed that the recombinant protein
      could react with rat serum immunized with Streptococcus suis, but not with non
      immunized rat serum. ELISA assay showed that anti-SSU1664 IgM content in
      Streptococcus suis-infected patient was significantly higher than that in healthy
      donors. CONCLUSION: The recombinant SSU1664 protein has immunogen activity and
      might be one promising Streptococcus suis vaccine candidate and diagnosis marker
      of Streptococcus suis early infection.

PMID- 21722529
TI  - [A preliminary study on the effect of lincomycin on the immune function of
      dendritic cell line DC2.4].
AB  - AIM: To explore the effect of lincomycin (lin) on the immune function of
      dendritic cell (DCs) line DC2.4. METHODS: Three experimental groups, namely,
      DC2.4 cells group, DC2.4 Cells+LPS group and DC2.4 cells +LPS +lin group were
      established (LPS and lin were 500 ng/mL). The morphological changes in each group
      were observed under inverted microscope. The MHC class II , CD86 and CD80 on the
      DC2.4 cells were detected by flow cytometer. The effects of lipopolysaccharide
      (LPS) and LPS +lin on the DC2.4 cells immuno-stimulatory capacity were evaluated
      by allogeneic mixed leukocytes reaction (MLR) between DC2.4 cells and T cells.
      ELISA was adopted to quantitate the level of IFN-gammain the supernatant of
      cultured DC2.4 cells and T cells in each group. RESULTS: DC2.4 cells showed
      typical morphology of immature DCs. When stimulated with LPS or LPS combined with
      lin, DC2.4 cells exhibited typical maturate DCs modality. LPS of 500 ng/mL could
      significantly up-regulate the expression of MHC class II , CD86 and CD80 on DC2.4
      cells and also augment stimulatory action of DC2.4 cells on T cells proliferation
      and secretion of IFN-gamma. However, compared with LPS alone, the treatment of
      lin (500 ng/mL) combined with LPS down-regulated the immmuno-regulation function
      of DC2.4 cells. CONCLUSION: Lin can partly inhibit the immuno-regulation function
      of maturate DC2.4 cells.

PMID- 21722530
TI  - [Construction and identification of BIRC5 shRNA lentiviral expression vector].
AB  - AIM: Design and synthesis complementary DNA sequences of 3 pairs of short hairpin
      structure and a pair of negative control sequence by RNA interference technique
      and construct and identify a lentiviral interference vector with human BIRC5 gene
      as target gene. METHODS: The designed and synthesised Single-Stranded primer were
      annealed to Double-Stranded oligo sequences and subcloned into linear pMAGic
      lentiviral plasmid vector digested by enzyme Age I and EcoR I. Screening positive
      clone after transformed into DH5alpha competent cells and identified by PCR
      amplification and DNA sequencing. RESULTS: 335 bp straps of positive clone and
      298 bp straps of negative clone form PCR amplification production have been
      obtained after gel electrophoresis, the designed and synthesised sequences have
      been contained in these clone straps confirmed by the result of DNA sequencing.
      CONCLUSION: Four pairs of BIRC5 shRNA recombinant lentiviral expression vector
      were constructed successfully, which laid the foundation for researching the
      inhibition of BIRC5 siRNA target against tumor cells proliferation, induction
      apoptosis and gene therapy.

PMID- 21722531
TI  - [Synthesis of artificial antigens of amoxicillin and preparation of monoclonal
      antibody to amoxicillin].
AB  - AIM: To synthesize two kinds of amoxicillin artificial antigen and to establish
      hybridoma cell lines secreting monoclonal antibody against amoxillin. METHODS:
      Amoxicillin were respectively coupled with ovalbumin(OVA) and bovine serum
      albumin(BSA) by using N-hydroxysuc-cinimide active ester (NHS) method to prepared
      the immunogen and detection antigen. Molar ratio of conjugates were detected by
      ultraviolet spectrum analysis. BALB/c mice was immunized with AMX-OVA. The
      hybridomas were obtained by fusing mouse myeloma cells Sp2/0 with splenocytes
      from the mice immunized with AMX-OVA. The aseites with mAb were purified by
      octanoic acid-saturated ammonium sulphate method. Isotype was determined by Mouse
      Isotype kit (Bio-RadLabs.). RESULTS: UV spectra shows overlay features between a
      small molecular compound and carrier protein. Five hybridoma cell strains
      secreting specific mAb against amoxicillin were obtained and the five Amb belong
      to IgG1 kappa isotype. The limit of detection of AMX was 0.25 ng/mL and but there
      is mild degree of cross-reactions with ampicillin with same structure of beta
      lactam ring. CONCLUSION: The anti-AMX Amb could be used to develop immunoassay
      for detection of residues.

PMID- 21722532
TI  - [Development and characterization of monoclonal antibody against human FcR gamma
      chain].
AB  - AIM: The current study was aimed to generate mouse monoclonal antibodies (mAbs)
      specific for Fc receptor common gamma chain (FcRgamma), which serves a critical
      signaling molecule for numerous human immune receptors that play essential roles
      in human immune responses. METHODS: Two BALB/c mice were immunized with the
      synthesized polypeptides containing 19 residues at the carboxyl terminus of human
      FcR gamma chain. The spleen cells from the immunized mice were fused with myeloma
      Sp2/0 cells. ELISA was used to screen mAbs and the positive clones were selected
      for further characterization with Western blot and flow cytometry assays.
      RESULTS: After screen, there hybridoma cell lines which secreted mAbs
      specifically recognized the FcR gamma chain were obtained and named as 5B6, 7D3
      and 8D4. The 7D3 mAb had the best quality and it could recognize the FcR gamma
      chain in vivo and in vitro with 2.5 MUg/mL. CONCLUSION: We have generated the
      FcRgamma-specific mAbs, which may serve as a valuable tool in the functional
      studies of FcRgamma associated immune receptors.

PMID- 21722533
TI  - [Production and characterization of the monoclonal antibodies against
      nonstructural 1 protein of DENV-4].
AB  - AIM: To produce monoclonal antibodies (mAbs) against nonstructural 1 protein
      (NS1) of DENV-4 and characterization. METHODS: BALB/c mice were immunized with
      recombinant DENV4-NS1 protein and inactive DENV-4. Splenocytes of immunized mice
      were fused with myeloma cells (NS-1) to produce hybridoma cell lines, secreting
      anti-DENV4-NS1 protein mAbs. ELISA was used to identify the mAbs against NS1of
      DENV-4. Immnofluorescence assay (IFA) and Western blot analysis were applied to
      identify the specificity of mAbs. RESULTS: fifteen mAbs recognizing two different
      antigenic epitopes on NS1of DENV-4 were obtained. These mAbs had characteristics
      of specific binding to recombinant NS1 of DENV-4. The IFA showed that all of the
      mAbs strongly reacted to DENV-4, while had no cross-reactivity to the other three
      serotypes of dengue virus. CONCLUSION: mAbs against NS1 of DENV-4 with high
      specificity has been successfully established. These results lay the foundation
      value for study on the structural and functional of DENV4-NS1 protein and early
      diagnosis of DENV-4 infection.

PMID- 21722534
TI  - [Prepared the monoclonal antibody associated with hepatocellular carcinoma and
      analyzed its epitope].
AB  - AIM: To prepare the monoclonal antibodies associated with hepatocellular
      carcinoma (HCC) for diagnosis. METHODS: 3 BALB/c mice were immunized with high
      metastasis characteristic HCC cells (HCCLM-6). The splenocytes from the immunized
      mice were fused with murine myeloma cells (Sp2/0). The hybridoma cells were
      screened by ELISA after coating with the total protein and the culture
      supernatant of HCCLM-6 cells. The mAbs were characterized by immunohistochemical
      staining in the HCC tissues, and by indirect immunofIuorescent staining in
      different cell lines. The antigen and epitope recognized by the mAbs were
      identified by the screening premade Uni-ZAP human liver cDNA expression library.
      RESULTS: Twenty-eight hybridoma cells secreting mAbs were established. One clone
      of the hybridomas, QGA062, secreted specific mAb associated with HCC. The antigen
      recognized by the mAb QGA062 was identified as fibronectin (FN), and the epitope
      was localized among the peptide YTVSLVAIKGNQESPK. CONCLUSION: The mAb against a
      HCC-associated epitope in FN is established and characterized, will be a very
      useful reagent for diagnosis of HCC.

PMID- 21722535
TI  - [Analysis for post-transplant changes of peripheral lymphocyte subsets in liver
      transplant receptors with HBV infection].
AB  - AIM: To investigate the characters and changes of peripheral lymphocyte subsets
      and cytokines in liver transplant receptors with HBV infection in short phases
      after liver transplantation, and to provide evidences for monitoring post
      transplant immune condition of liver transplant receptors. METHODS: Peripheral
      lymphocyte subsets and cytokine levels in pre- and post- transplant 12 h, 3 d, 10
      d, 30 d, 60 d of 20 cases of patients with HBV-associated severe hepatic diseases
      were investigated and analyzed, and were compared respectively with those of 22
      cases of healthy adults as control (HC) with flow cytometry (FCM) and ELISA.
      RESULTS: The patients' accounts of peripheral lymphocyte subsets before liver
      transplantation were lower than those of HC significantly, but the accounts
      decreased significantly after transplantation 12 h. Three days later, the
      accounts of lymphocyte subsets increased significantly. The percentages of CD3,
      CD4, CD8 and NK cells got to stable stage from post-transplantation 10 d, and the
      absolute accounts of post-transplantation 60 d were higher than those of pre
      transplantation, but were still lower than those of HC; The IFN-gamma and IL-10
      levels of post-transplantation 12 h increased several times and decreased after 3
      days. The IL-10 levels in post-transplantation 60 d were still higher than those
      of HC. CONCLUSION: The absolute accounts of peripheral lymphocyte subsets
      increased to stable levels from post-transplantation 10 d, but were still lower
      than those of HC; Post-transplant immune condition was to Th2 polarization.

PMID- 21722536
TI  - [Effect of curcumol on proliferation and apoptosis of nasopharyngeal carcinoma
      cell line CNE-2].
AB  - AIM: To investigate the effect of curcumol on the proliferation, apoptosis and
      the expression NF-kappaB in nasopharyngeal carcinoma cell line CNE-2. METHODS:
      CNE-2 cells were treated with curcumol at different concentration(12.5, 25, 50,
      100 mg/L) and the control group; the effect of proliferation was detected by MTT
      method; the apoptosis was analyzed by hoechst 33342 flourescence staning and flow
      cytometry; the expression of NF-kappaB was detected with western blotting.
      RESULTS: After treated with curcumol, CNE-2 cell's proliferation was
      significantly reduced (P<0.01) and its apoptosis was increased as the curcumol
      concentration rising, the apoptosis of 100 mg/L curcumol group even can reach to
      45.5% and it was a significantly difference compared with control group (P<0.01);
      the expression of NF-kappaB was down regulated as raising the curcumol
      concentration, there was a significantly difference compared with control group
      (P<0.01). CONCLUSION: Curcumol is capable of significantly inhibiting
      proliferation and inducing apoptosis of CNE-2' cells in vitro, the mechanism of
      curcumol anti-tumor may be related to the down regulated of the NF-kappaB protein
      level.

PMID- 21722537
TI  - Immunodeficiencies in children with chronic post tympanic otorrhoea.
AB  - INTRODUCTION: A minority of children treated with ventilation tubes develop
      chronic otorrhoea. To test the hypothesis that this condition might be caused by
      an underlying primary immunodeficiency, the immunological status was examined in
      a group of children with longstanding otorrhoea. MATERIAL AND METHODS: Eighteen
      children who had suffered from otorrhoea for a minimum of six months and who did
      not respond to relevant therapy were included. Thorough cleansing and suction was
      performed including removal of ventilation tubes. Swabs were obtained for
      microbiology and blood was collected for immunological analyses. RESULTS: One
      child out of 18 had a normal immune status. Five demonstrated isolated humoral
      deficiencies, four had isolated cellular deficiencies, whereas combined defects
      were identified among eight children. The humoral deficiencies consisted of
      selective or partial immunoglobulin A deficiencies, immunoglobulin G subclass and
      mannanbinding lectin deficiencies. The cellular deficiencies most often involved
      the cytotoxic T cells and the natural killer cells. CONCLUSION: Primary
      immunodeficiencies were very prevalent in a highly selected group of children
      suffering from longstanding post tympanic otorrhoea. The condition should
      therefore be considered in case of chronic, refractory otorrhoea. The serostatus
      should be followed carefully to obtain information of the prognosis. FUNDING: Not
      relevant. TRIAL REGISTRATION: Not relevant.

PMID- 21722538
TI  - Symptoms and time to diagnosis in children with brain tumours.
AB  - INTRODUCTION: Clinical symptoms in brain tumours in children are variable at
      onset and diagnosis is often delayed. Symptoms were investigated with regard to
      brain tumour localisation, prediagnostic symptomatic intervals and malignancy.
      MATERIAL AND METHODS: Clinical data from children aged 0-17 years from Southern
      Denmark were analysed retrospectively and the results were correlated with data
      on prehospital symptoms obtained from interviews with parents and general
      practitioners. RESULTS: A total of 55 children diagnosed during a period of five
      years were indentified and 31 interviews were obtained. A total of 19 (41%) of
      the tumours were supratentorial hemispheric and midline and 27 (59%) were
      infratentorial. At supratentorial localisations, 42% experienced vomiting as
      their first symptom followed by seizures in 37% and headache in 31%. At
      infratentorial localisations, headache occurred in 62%, vomiting in 55% and
      ataxia in 48% of the cases. The prediagnostic symptomatic interval had a median
      duration of 30 days with vomiting (range 3-330 days), a median of 75 days with
      headache (5-730 days) and a median of 75 days with ataxia (1-730 days).
      CONCLUSION: Diagnosis is often late in relation to the presenting symptoms. An
      earlier diagnosis may be achieved if a brain tumour is considered as soon as any
      child presents with the relevant symptoms. FUNDING: Not relevant. TRIAL
      REGISTRATION: ISRCTN88306789.

PMID- 21722539
TI  - Utility of 18FDG-PET/CT in breast cancer diagnostics--a systematic review.
AB  - 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG
      PET/CT) is a non-invasive method for visualization of focally increased
      metabolism in the presence of discrete morphological changes. Based on a
      systematic review of current literature, PET/CT cannot be recommended as a
      primary diagnostic procedure in breast cancer; but it has the potential to be
      useful for the detection of distant metastases and for monitoring response to
      chemotherapy in breast cancer patients. PET/CT should still be regarded as a
      supplement to conventional diagnostic procedures such as CT and MRI.

PMID- 21722540
TI  - Optimised diagnosis and treatment of necrotizing external otitis is warranted.
AB  - INTRODUCTION: Necrotizing external otitis (NEO) is a devastating and life
      threatening infection in the external auditory canal and the temporal bone. The
      aim of this paper is to evaluate the diagnostics and treatment of NEO and to
      recommend new guidelines. MATERIAL AND METHODS: Eleven patients were
      retrospectively enrolled under the code DH609 otitis externa without
      specification from 1 January 2000 to 31 December 2009. Records were reviewed to
      register: age, symptoms, clinical findings, comorbidity, imaging, microbiology
      and treatment. RESULTS: The median age was 75 years and the median time of
      therapy at the hospital was 6.3 months. All patients belonged to a risk group. A
      diagnostic delay was found resulting in further progression of the disease. In
      contrast to current international recommendations, the treatment consisted mostly
      of local antibiotics in combination with surgery. All patients survived, but most
      patients were left with hearing loss and psychiatric problems. CONCLUSION: A
      greater awareness of diagnostic criteria and a shift from local antibiotics to
      prolonged systemic monotherapy with ciprofloxacin in accordance with
      international concepts is recommended. Surgery should be left for extensive and
      refractory cases only. A list of diagnostic criteria and treatment guidelines is
      presented. FUNDING: Not relevant. TRIAL REGISTRATION: Not relevant.

PMID- 21722541
TI  - Similar recovery rates of Fusobacterium necrophorum from recurrently infected and
      non-infected tonsils.
AB  - INTRODUCTION: Recent studies implicate the presence of Fusobacterium necrophorum
      (FN) in recurrent tonsillitis (RT), acute tonsillitis and peritonsillar abscess.
      The objective of the present study was to determine whether FN plays a role in RT
      by comparing bacteriologic results from patients suffering from RT, tonsillar
      hypertrophy and halitosis or persistent sore throat syndrome (PSTS). We analyzed
      both tonsils to determine the degree of concordance. MATERIAL AND METHODS: A
      prospective study was conducted in 80 patients aged 8-30 years who were
      undergoing elective tonsillectomy. The patients were divided into four groups
      according to indication for surgery. Aerobic and anaerobic cultures from the
      tonsillar surface and core were analyzed. RESULTS: FN was detected less
      frequently in the tonsillar cores of RT patients (22%) than in those of patients
      without RT (30%) (p=0.44). FN detection frequencies ranged between 20% and 35%
      across the four groups. Betahaemolytic streptococci groups A/C/G (BHS) were
      detected significantly (p=0.007) more often in the RT group than in the
      halitosis/PSTS group. CONCLUSION: A possible role of FN in RT was not
      substantiated. Our results indicate that FN is likely to be part of the normal
      flora. The tonsillar surface and core flora carry considerable interpersonal
      diversity, but is very similar bilaterally in each individual. Other factors seem
      to play a major role in the development of the represented tonsillar diseases.
      FUNDING: Not relevant. TRIAL REGISTRATION: The study was approved by The Research
      Ethics Committee of Aarhus County (no. 20050034).

PMID- 21722542
TI  - Prolonged length of stay and many readmissions after appendectomy.
AB  - INTRODUCTION: The epidemiology of appendicitis seems to be changing; the
      proportion of complicated appendicitis cases is growing. The outcome of childhood
      appendectomy in Denmark has not previously been evaluated nationwide in Denmark.
      MATERIAL AND METHODS: Data on all Danish children treated for appendicitis were
      obtained from the National Patient Registry. Reoperation, readmittance or length
      of hospital stay (LOS) exceeding five days were considered nonsatisfactory
      outcomes. RESULTS: A total of 2,617 children, 55% boys and 45% girls, were
      operated at 32 hospitals. Their mean age was 11.1 years. Mortality was 0%. A
      laparoscopic procedure was used in 34% of the cases. The medians of the
      postoperative LOS were one day for both the open and laparoscopic appendectomy
      groups, the corresponding means were 2.5 and 2.0 days (p<0.05). 4.5% had one or
      more reoperations. 18% had a LOS>5 days or readmittance. The typical reasons were
      wound infection, need for prolonged antibiotics treatment and simple, prolonged
      recovery. CONCLUSION: The Danish practice for appendicitis has acceptable rates
      of reoperation, medians and means of LOS, and a rate of readmission which is
      comparable to that reported in other studies. However, a nonsatisfactory outcome
      after appendectomy in about 20% calls for improvement and further studies.
      FUNDING: Not relevant. TRIAL REGISTRATION: Not relevant.

PMID- 21722543
TI  - Acceptable long-term outcome in elderly intensive care unit patients.
AB  - INTRODUCTION: The number of elderly intensive care unit (ICU) patients is
      increasing. We therefore assessed the long-term outcome in the elderly following
      intensive care. MATERIAL AND METHODS: The outcome status for 91 elderly (=75
      years) and 659 nonelderly (18-74 years) ICU patients treated in the course of a
      one year period was obtained. A total of 36 of 37 eligible elderly survivors were
      interviewed about their health related quality of life (HRQOL), social services
      and their wish for intensive care. RESULTS: The mortality (54% at follow-up and
      64% after one year) was higher in the elderly ICU patients than in non-elderly
      ICU patients (33% and 37%, respectively, p<0.001) and than in the Danish
      background population>=75 years (9%, p<0.001). Elderly ICU survivors had
      significantly lower HRQOL scores in two of four physical domains and a lower
      physical component summary score than age matched controls (38 (31-46) versus 43
      (36-52), p=0.01). However, ICU survivors scored like controls in three of four
      mental domains and higher than controls in "mental health" (p=0.04). At follow
      up, 89% had returned to live in their own home. CONCLUSION: Elderly ICU patients
      had high long-term mortality rates and survivors had impaired physical function.
      Nevertheless, their mental function was in line with that of the background
      population and the majority had returned to their home and wished intensive care
      again. FUNDING: The study was supported only by Rigshospitalet's Research
      Council. TRIAL REGISTRATION: Not relevant.

PMID- 21722544
TI  - Promising results after percutaneous mitral valve repair.
AB  - INTRODUCTION: Mitral valve regurgitation (MR) is the secondmost frequent valve
      disease in Europe. Untreated MR causes considerable morbidity and mortality. In
      the elderly, as many as half of these patients are denied surgery because of an
      estimated high surgical risk. Percutaneous mitral valve repair with the MitraClip
      system resembles the Alfieristitch where a clip is used to connect the tip of the
      mitral valve leaflets. MATERIAL AND METHODS: Sixteen patients with MR of various
      origins (functional/degenerative) were treated with the MitraClip system. All
      patients were highly symptomatic with dyspnoea (New York Heart Association (NYHA)
      grade three) and MR grade three or more, and had been turned down for surgery due
      to an excessively high risk. RESULTS: MR was reduced in all but one patient,
      generally from grade 3.5+/-0.5 to grade 1.4+/-0.9. A total of four patients (25%)
      received two clips. Thirty-day complications were as follows: one patient died,
      one had a stroke (speech sequelae), one patient had a new chord rupture that was
      treated surgically. During 90 days of follow-up, symptoms of dyspnoea diminished
      (reduction of 1 NYHA grade) and the 6-minute walk test results improved from
      171+/-99 to 339+/-134 metres (p<0.001). CONCLUSION: Percutaneous mitral valve
      repair with the MitraClip system is now available in Denmark. The treatment is a
      reasonable alternative in patients with MR and a high estimated surgery risk.
      FUNDING: Not relevant. TRIAL REGISTRATION: Not relevant.

PMID- 21722545
TI  - Severe agitation following deep brain stimulation for parkinsonism.
AB  - The use of deep brain stimulation has become increasingly common for the
      treatment of movement disorders, including Parkinson disease. Although deep brain
      stimulation is generally very successful in alleviating the extrapyramidal
      symptoms of Parkinson disease, side effects can occur. This case report describes
      a patient presenting to the emergency department in a state of extreme aggression
      3 days after a change in the parameters of his bilateral subthalamic nucleus
      stimulator. We review the complications of deep brain stimulation relevant to the
      emergency physician and provide some practical information on stimulator
      adjustment in an emergency.

PMID- 21722547
TI  - Re: Dilute proparacaine for the management of acute corneal injuries in the
      emergency department. CJEM 2010;12:389-94.

PMID- 21722548
TI  - Re: Hookworm-related cutaneous larva migrans. CJEM 2010;12:446.

PMID- 21722549
TI  - Mass gathering medicine: a practical means of enhancing disaster preparedness in
      Canada.
AB  - BACKGROUND: We explore the health care literature and draw on two decades of
      experience in the provision of medical care at mass gatherings and special events
      to illustrate the complementary aspects of mass gathering medical support and
      disaster medicine. Most communities have occasions during which large numbers of
      people assemble in public or private spaces for the purpose of celebrating or
      participating in musical, sporting, cultural, religious, political, and other
      events. Collectively, these events are referred to as mass gatherings. The
      planning, preparation, and delivery of health-related services at mass gatherings
      are understood to be within the discipline of emergency medicine. As well, we
      note that owing to international events in recent years, there has been a
      heightened awareness of and interest in disaster medicine and the level of
      community preparedness for disasters. We propose that a synergy exists between
      mass gathering medicine and disaster medicine. METHOD: Literature review and
      comparative analysis. RESULTS: Many aspects of the provision of medical support
      for mass gathering events overlap with the skill set and expertise required to
      plan and implement a successful medical response to a natural disaster, terrorist
      incident, or other form of disaster. CONCLUSIONS: There are several practical
      opportunities to link the two fields in a proactive manner. These opportunities
      should be pursued as a way to improve the level of disaster preparedness at the
      municipal, provincial, and national levels.

PMID- 21722550
TI  - On your mark: emergency medicine and the Vancouver Olympic Games.

PMID- 21722552
TI  - Examination of staphylococcal stethoscope contamination in the emergency
      department (pilot) study (EXSSCITED pilot study).
AB  - INTRODUCTION: The objective of this study was to determine the prevalence of
      Staphylococcus-contaminated stethoscopes belonging to emergency department (ED)
      staff and to identify the proportion of these that were Staphylococcus aureus or
      methicillin-resistant Staphylococcus aureus (MRSA). METHODS: We conducted a
      prospective observational cohort study of bacterial cultures from 100 ED staff
      members' stethoscopes at three EDs. Study participants were asked to complete a
      questionnaire. RESULTS: Fifty-four specimens grew coagulase-negative
      staphylococci and one grew methicillin-susceptible S. aureus. No MRSA was
      cultured. Only 8% of participants, all of whom were nurses, reported cleaning
      their stethoscope before or after each patient assessment. Alcohol-based wipes
      were most commonly used to clean stethoscopes. A lack of time, being too busy,
      and forgetfulness were the most frequently reported reasons for not cleaning the
      stethoscope in the ED. CONCLUSIONS: This study indicates that although
      stethoscope contamination rates in these EDs are high, the prevalence of S.
      aureus or MRSA on stethoscopes is low.

PMID- 21722553
TI  - Bedside ultrasonography detects significant femoral vessel overlap: implications
      for central venous cannulation.
AB  - OBJECTIVE: Our goal was to gain a better understanding of the femoral vessel
      anatomy as it relates to central venous cannulation. The primary objective of
      this study was to use bedside ultrasonography to determine the amount of exposed
      femoral vein at three sites corresponding to surface anatomy of the landmark
      based procedure. METHODS: This cross-sectional study enrolled a random sample of
      180 adult patients presenting to a large urban academic emergency department.
      Subjects underwent standardized ultrasonography to identify and measure the depth
      and diameter of the femoral vessels and amount of exposed femoral vein at the
      level of the inguinal ligament (0 cm) 2 cm and 4 cm below. Repeated measures
      analysis of variance was used to determine significant relationships between
      vessel measurements and distance from the inguinal ligament. RESULTS: The median
      age was 44.5 (range 19-90) years; 101 patients were male. The mean (+/- SD)
      percentage of exposed vein at the inguinal ligament was 83% (+/- 21). This
      decreased significantly (p < 0.01) with increasing distance from the inguinal
      ligament: 65% (+/- 25) at 2 cm and 56% (+/- 30) at 4 cm. At every distance away
      from the inguinal ligament, there were some subjects with no vein exposed.
      CONCLUSION: This study demonstrates significant overlap of the femoral vessels at
      sites where landmark-based femoral vein cannulation is often attempted. Our
      results suggest that ultrasound guidance would be beneficial as femoral vein
      cannulation may be difficult or impossible in certain individuals owing to
      anatomic variations.

PMID- 21722554
TI  - Emergency medicine training in Canada: a survey of medical students' knowledge,
      attitudes, and preferences.
AB  - OBJECTIVES: The objective of this study was to assess medical students' knowledge
      of and attitudes toward the two Canadian emergency medicine (EM) residency
      programs (Fellow of the Royal College of Physicians of Canada [FRCPC] and
      Certificant of the College of Family Physicians-Emergency Medicine [CCFP-EM]).
      Additionally, medical students interested in EM were asked to select factors
      affecting their preferred choice of residency training program and their intended
      future practice. METHODS: Medical students enrolled at The University of Western
      Ontario for the 2008-2009 academic year were invited to complete an online 47
      item questionnaire pertaining to their knowledge, opinions, and attitudes toward
      EM residency training. RESULTS: Of the 563 students invited to participate, 406
      (72.1%) completed the survey. Of the respondents, 178 (43.8%) expressed an
      interest in applying to an EM residency training program, with 85 (47.8%) most
      interested in applying to the CCFP-EM program. The majority of respondents
      (54.1%) interested in EM believed that there should be two streams to EM
      certification, whereas 18.0% disagreed. Family life and control over work
      schedule appeared to be common priorities seen as benefits of any career in EM.
      Other high-ranking factors influencing career choice differed between the groups
      interested in CCFP-EM and FRCPC. The majority of students interested in the CCFP
      EM residency program (78%) reported that they intend to blend their EM with their
      family medicine practice. Only 2% of students planned to practice only EM with no
      family medicine. CONCLUSIONS: This is the first survey of Canadian medical
      students to describe disparities in factors influencing choice of EM residency
      stream, perceptions of postgraduate work life, and anticipated practice
      environment.

PMID- 21722555
TI  - Impact of a teaching attending physician on medical student, resident, and
      faculty perceptions and satisfaction.
AB  - OBJECTIVES: To determine if a dedicated teaching attending for medical student
      education improves medical student, attending physician, and resident perceptions
      and satisfaction. METHODS: Two dedicated teaching attending physician shifts were
      added to the clinical schedule each week. A before-after trial compared medical
      student evaluations from 2000 to 2004 (preteaching attending physician) to
      medical student evaluations from 2005 to 2006 (teaching attending physician).
      Attending physician and resident perceptions and satisfaction with the teaching
      attending physician shifts using a 5-point Likert-type scale (1  =  poor to 5  = 
      excellent) were also assessed. RESULTS: Eighty-nine (100%) medical students
      participated, with 63 preteaching attending physician and 26 teaching attending
      physician rotation evaluations. The addition of teaching attending physician
      shifts improved mean medical student satisfaction with bedside teaching (4.1 to
      4.5), lecture satisfaction (4.2 to 4.8), preceptor scores (4.3 to 4.8), and
      perceived usefulness of the rotation (4.5 to 5.0) (all p < 0.05). Thirteen
      attending physicians (93%) participated in the cross-sectional questionnaire. The
      addition of teaching attending physician shifts improved faculty ratings of their
      medical student interactions by >= 1.5 points for all items (p <= 0.001). Faculty
      perceptions of their resident interactions improved for quality of bedside
      teaching (3.1 to 4.0), their availability to hear resident presentations (3.4 to
      4.2), and their supervision of residents (3.4 to 4.1) (p <= 0.01). Residents (n 
      =  35) noted minor improvements with the timeliness of patient dispositions,
      faculty bedside teaching, and attending physician availability. CONCLUSIONS: The
      addition of select teaching attending physician shifts had the greatest effect on
      medical student and faculty perceptions and satisfaction, with some improvements
      for residents.

PMID- 21722556
TI  - How do I improve the quality of in-training assessment of learners?
AB  - Assessing a learner in the course of a hectic emergency department (ED) rotation
      is a daunting task for both experienced and new supervisors. This is particularly
      true if the learner is not doing well. In light of numerous impediments provided
      by the modern ED environment, sticking to basic principles can result in marked
      improvement in both the process and the outcome of in-training assessment. This
      article addresses these important principles for assessment as they apply in the
      clinical realm of the ED, with a focus on matching expectations to both the
      trainee and the available assessment strategies. It is critical that teachers
      strive for clarity, consistency, honesty, and adherence to due process in their
      learner assessments. This article provides an evidence-informed approach to
      succeeding with such an approach to clinical assessment.

PMID- 21722557
TI  - Steroids for patients in septic shock: the results of the CORTICUS trial.
AB  - CLINICAL QUESTION: What is the role of steroids in septic shock in the emergency
      department? ARTICLE CHOSEN: Sprung CL, Annane D, Keh D, et al; CORTICUS Study
      Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med
      2008;358:111-24. STUDY OBJECTIVE: To assess the safety and efficacy of low-dose
      hydrocortisone therapy for patients with septic shock and to compare outcomes
      based on response to corticotropin testing.

PMID- 21722558
TI  - Corneal limbal foreign bodies.

PMID- 21722560
TI  - Take my breath away: a case of lactic acidosis in an asthma exacerbation.
AB  - A 36-year-old male with a history of chronic asthma presented to an emergency
      department with shortness of breath consistent with an asthma exacerbation. He
      had persistent tachypnea following inhaled bronchodilator treatment; thus, the
      workup and differential diagnosis were expanded. He was found to have a mixed
      respiratory alkalosis and metabolic acidosis with elevated serum lactate without
      an obvious cause and was admitted to hospital. His case was reviewed, and the
      lactic acidosis was thought to be caused by inhaled beta2-agonist use. Emergency
      physicians should be aware of the potential side effects of inhaled beta2
      agonists as lactic acidosis may complicate clinical assessment and management of
      asthma exacerbations and lead to unnecessary and potentially dangerous
      escalations in therapy.

PMID- 21722561
TI  - How to give a consultation and how to get a consultation.

PMID- 21722562
TI  - Smart sensors for maintaining physiologic homeostasis.

PMID- 21722563
TI  - Data standards in diabetes patient registries.
AB  - Widespread adoption of electronic health records (EHRs) and expansion of patient
      registries present opportunities to improve patient care and population health
      and advance translational research. However, optimal integration of patient
      registries with EHR functions and aggregation of regional registries to support
      national or global analyses will require the use of standards. Currently, there
      are no standards for patient registries and no content standards for health care
      data collection or clinical research, including diabetes research. Data standards
      can facilitate new registry development by supporting reuse of well-defined data
      elements and data collection systems, and they can enable data aggregation for
      future research and discovery. This article introduces standardization topics
      relevant to diabetes patient registries, addresses issues related to the quality
      and use of registries and their integration with primary EHR data collection
      systems, and proposes strategies for implementation of data standards in diabetes
      research and management.

PMID- 21722564
TI  - Identifying type 1 and type 2 diabetic cases using administrative data: a tree
      structured model.
AB  - BACKGROUND: To date, few administrative diabetes mellitus (DM) registries have
      distinguished type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus
      (T2DM). OBJECTIVE: Using a classification tree model, a prediction rule was
      developed to distinguish T1DM from T2DM in a large administrative database.
      METHODS: The Medical Archival Retrieval System at the University of Pittsburgh
      Medical Center included administrative and clinical data from January 1, 2000,
      through September 30, 2009, for 209,647 DM patients aged >=18 years. Probable
      cases (8,173 T1DM and 125,111 T2DM) were identified by applying clinical criteria
      to administrative data. Nonparametric classification tree models were fit using
      TIBCO Spotfire S+ 8.1 (TIBCO Software), with model size based on 10-fold cross
      validation. Sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) of T1DM were estimated. RESULTS: The main
      predictors that distinguished T1DM from T2DM are age <40 years; International
      Classification of Disease, 9th revision, codes of T1DM or T2DM diagnosis;
      inpatient oral hypoglycemic agent use; inpatient insulin use; and episode(s) of
      diabetic ketoacidosis diagnosis. Compared with a complex clinical algorithm, the
      tree-structured model to predict T1DM had 92.8% sensitivity, 99.3% specificity,
      89.5% PPV, and 99.5% NPV. CONCLUSION: The preliminary predictive rule appears to
      be promising. Being able to distinguish between DM subtypes in administrative
      databases will allow large-scale subtype-specific analyses of medical care costs,
      morbidity, and mortality.

PMID- 21722565
TI  - The association between driving distance and glycemic control in rural areas.
AB  - BACKGROUND: In order to optimize care and improve outcomes in people with
      diabetes, adequate access to health care facilities and resources for self
      management is required. METHODS: Data on 3369 individuals with type 2 diabetes
      who received education at 7 diabetes centers were collected prospectively between
      June 2005 and January 2007. The driving distances of subjects who were in good
      control [hemoglobin A1c (A1C) <=7.0%] were compared with the driving distances of
      those who were not (A1C >7.0%). The association between A1C and improvement in
      A1C with travel burden was tested. RESULTS: The mean distance subjects traveled
      to visit their center was 13.3 miles. The results indicated that residing more
      than 10 miles from the diabetes management center [odds ratio (OR) = 1.91, p <
      .0001], being younger (OR = 0.99, p = .00015), and having a longer duration of
      diabetes (OR = 1.03, p = .0007) were significant contributors to a A1C >7%
      adjusted for individual- and community-level factors. In addition, those who
      lived within 10 miles of their center were 2.5 times more likely to have improved
      their A1C values between their first and last office visits. CONCLUSION: Health
      care providers should be aware of travel burden as a potential barrier to
      glycemic control. In the future, it may be useful to minimize driving distance
      for individuals with diabetes, perhaps by improved public transportation, more
      diabetes center locations in rural areas, telemedicine, or home visits.

PMID- 21722566
TI  - Cost-effectiveness of implementing the chronic care model for diabetes care in a
      military population.
AB  - BACKGROUND: Applying the chronic care model (CCM) for diabetes management helps
      improve health outcomes and patient care. The CCM was implemented at U.S. Air
      Force Wilford Hall Medical Center through the Diabetes Outreach Clinic (DOC) in
      2006, but its cost-effectiveness in this setting is unknown. METHODS: We
      constructed a Markov decision model to estimate DOC cost-effectiveness compared
      with usual care (UC) over a 20-year period. Based on empirical, post-intervention
      demographic and clinical data, we applied United Kingdom Prospective Diabetes
      Study risk equations to predict long-term probabilities of developing
      microvascular or macrovascular complications. Health care system and societal
      perspectives were considered, discounting costs and benefits at 3% annually.
      Intervention costs and outcomes were obtained from military data, while other
      costs, disease progression data, and utilities were drawn from published
      literature. RESULTS: From a health care system perspective, the DOC cost $45,495
      per quality-adjusted life-year (QALY) compared with UC; from a societal
      perspective, the DOC compared with UC cost $42,051/QALY (when the model started
      with the uncomplicated diabetes cohort), $61,243/QALY (when starting with the DOC
      cohort), or $61,813/QALY (when starting with the UC cohort). In one-way
      sensitivity analyses, results were most sensitive to yearly costs for specialty
      care visits. In probabilistic sensitivity analysis, the DOC was favored in 51% of
      model iterations using an acceptability threshold of $50,000/QALY and in 72% at a
      threshold of $100,000/QALY. CONCLUSIONS: The DOC strategy for diabetes care,
      performed with the CCM methodology in a military population, appears to be
      economically reasonable compared with UC.

PMID- 21722567
TI  - Building a diabetes screening population data repository using electronic medical
      records.
AB  - There has been a rapid advancement of information technology in the area of
      clinical and population health data management since 2000. However, with the fast
      growth of electronic medical records (EMRs) and the increasing complexity of
      information systems, it has become challenging for researchers to effectively
      access, locate, extract, and analyze information critical to their research. This
      article introduces an outpatient encounter data framework designed to construct
      an EMR-based population data repository for diabetes screening research. The
      outpatient encounter data framework is developed on a hybrid data structure of
      entity-attribute-value models, dimensional models, and relational models. This
      design preserves a small number of subject-specific tables essential to key
      clinical constructs in the data repository. It enables atomic information to be
      maintained in a transparent and meaningful way to researchers and health care
      practitioners who need to access data and still achieve the same performance
      level as conventional data warehouse models. A six-layer information processing
      strategy is developed to extract and transform EMRs to the research data
      repository. The data structure also complies with both Health Insurance
      Portability and Accountability Act regulations and the institutional review
      board's requirements. Although developed for diabetes screening research, the
      design of the outpatient encounter data framework is suitable for other types of
      health service research. It may also provide organizations a tool to improve
      health care quality and efficiency, consistent with the "meaningful use"
      objectives of the Health Information Technology for Economic and Clinical Health
      Act.

PMID- 21722568
TI  - Using web technology to support population-based diabetes care.
AB  - BACKGROUND: Managed clinical networks have been used to coordinate chronic
      disease management across geographical regions in the United Kingdom. Our
      objective was to review how clinical networks and multidisciplinary team-working
      can be supported by Web-based information technology while clinical requirements
      continually change. METHODS: A Web-based population information system was
      developed and implemented in November 2000. The system incorporates local
      guidelines and shared clinical information based upon a national dataset for
      multispecialty use. Automated data linkages were developed to link to the master
      index database, biochemistry, eye screening, and general practice systems and
      hospital diabetes clinics. Web-based data collection forms were developed where
      computer systems did not exist. The experience over the first 10 years (to
      October 2010) was reviewed. RESULTS: The number of people with diabetes in
      Tayside increased from 9694 (2.5% prevalence) in 2001 to 18,355 (4.6%) in 2010.
      The user base remained stable (~400 users), showing a high level of clinical
      utility was maintained. Automated processes support a single point of data entry
      with 10,350 clinical messages containing 40,463 data items sent to external
      systems during year 10. The system supported quality improvement of diabetes
      care; for example, foot risk recording increased from 36% in 2007 to 73.3% in
      2010. CONCLUSIONS: Shared-care datasets can improve communication between health
      care service providers. Web-based technology can support clinical networks in
      providing comprehensive, seamless care across a geographical region for people
      with diabetes. While health care requirements evolve, technology can adapt,
      remain usable, and contribute significantly to quality improvement and working
      practice.

PMID- 21722569
TI  - Disease registries on the nationwide health information network.
AB  - BACKGROUND: Donation by individuals of their protected health information (PHI)
      for evidence-based research potentially benefits all individuals with disease
      through improved understandings of disease patterns. In the future, a better
      understanding of how disease features combine into unique patterns of disease
      will generate new disease classifications, supporting greater specificity in
      health management techniques. However, without large numbers of people who donate
      their PHI to disease registries designed for research, it is difficult for
      researchers to discover the existence of complex patterns or to create more
      specific evidence-based management techniques. In order to identify new
      opportunities in disease registry design, an analysis of the current stage of
      maturity of the newly created U.S. Nationwide Health Information Network (NwHIN)
      related to large-scale consumer donation of PHI is presented. METHODS: Utilizing
      a use-case analysis methodology, the consumer-centric designs of the policies and
      technologies created for the NwHIN were examined for the potential to support
      consumer donations of PHI to research. RESULTS: The NwHIN design has placed the
      enforcement point for the policy-based release of PHI over the Internet into a
      specialized gateway accessible to consumer authorization. However, current NwHIN
      policies leave the final decision regarding release of PHI for research to the
      health care providers rather than to the consumers themselves. CONCLUSIONS:
      Should disease registries designed for research be established on the NwHIN,
      consumers might then directly authorize the donation of their PHI to these
      disease registries. However, under current NwHIN policies, consumer authorization
      does not guarantee release of PHI by health providers.

PMID- 21722570
TI  - Use of a large diabetes electronic medical record system in India: clinical and
      research applications.
AB  - BACKGROUND: The diabetes electronic medical record (DEMR) has emerged as an
      effective information management tool with the potential to improve diabetes care
      and research. This study reports on the usefulness of the DEMR system at Dr.
      Mohan's Diabetes Specialities Centre (DMDSC), Chennai, India, for clinical and
      research purposes. METHODS: The DEMR, set up in 1996 at DMDSC, connects data of
      nine centers/clinics in different geographical areas in Southern India. The
      present data analysis is based on a total of 226,228 patients registered in the
      DEMR system at DMDSC between the years 1991 and 2010. RESULTS: The DEMR included
      data of 139,906 male and 86,322 female patients, of whom 92.6% had type 2
      diabetes mellitus (T2DM), 1.4% had type 1 diabetes mellitus (T1DM), and the rest
      had other types. Patients with T2DM had higher prevalence rates of neuropathy
      (33.1% vs 13.0%, p < .001), microalbuminuria (25.5% vs 20.0%, p < .001), coronary
      artery disease (17.5% vs 9.2%, p < .001) and peripheral vascular disease (3.9% vs
      2.8%, p = .017) compared with T1DM patients, while prevalence of diabetic
      retinopathy was similar (37.9% vs 35.7%, p = .06). Prevalence of microvascular
      and macrovascular complications of diabetes increased with increasing glycated
      hemoglobin levels (p for trend < .001) and increasing diabetes duration (p for
      trend < .001). CONCLUSIONS: The DEMR helps track diabetes care and is a valuable
      tool for research.

PMID- 21722571
TI  - Review of electronic decision-support tools for diabetes care: a viable option
      for low- and middle-income countries?
AB  - CONTEXT: Diabetes care is complex, requiring motivated patients, providers, and
      systems that enable guideline-based preventative care processes, intensive risk
      factor control, and positive lifestyle choices. However, care delivery in low-
      and middle-income countries (LMIC) is hindered by a compendium of systemic and
      personal factors. While electronic medical records (EMR) and computerized
      clinical decision-support systems (CDSS) have held great promise as interventions
      that will overcome system-level challenges to improving evidence-based health
      care delivery, evaluation of these quality improvement interventions for diabetes
      care in LMICs is lacking. OBJECTIVE AND DATA SOURCES: We reviewed the published
      medical literature (systematic search of MEDLINE database supplemented by manual
      searches) to assess the quantifiable and qualitative impacts of combined EMR-CDSS
      tools on physician performance and patient outcomes and their applicability in
      LMICs. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria prespecified the
      population (type 1 or 2 diabetes patients), intervention (clinical EMR-CDSS tools
      with enhanced functionalities), and outcomes (any process, self-care, or patient
      level data) of interest. Case, review, or methods reports and studies focused on
      nondiabetes, nonclinical, or in-patient uses of EMR-CDSS were excluded.
      Quantitative and qualitative data were extracted from studies by separate single
      reviewers, respectively, and relevant data were synthesized. RESULTS: Thirty
      three studies met inclusion criteria, originating exclusively from high-income
      country settings. Among predominantly experimental study designs, process
      improvements were consistently observed along with small, variable improvements
      in risk-factor control, compared with baseline and/or control groups (where
      applicable). Intervention benefits varied by baseline patient characteristics,
      features of the EMR-CDSS interventions, motivation and access to technology among
      patients and providers, and whether EMR-CDSS tools were combined with other
      quality improvement strategies (e.g., workflow changes, case managers,
      algorithms, incentives). Patients shared experiences of feeling empowered and
      benefiting from increased provider attention and feedback but also frustration
      with technical difficulties of EMR-CDSS tools. Providers reported more efficient
      and standardized processes plus continuity of care but also role tensions and
      "mechanization" of care. CONCLUSIONS: This narrative review supports EMR-CDSS
      tools as innovative conduits for structuring and standardizing care processes but
      also highlights setting and selection limitations of the evidence reviewed. In
      the context of limited resources, individual economic hardships, and lack of
      structured systems or trained human capital, this review reinforces the need for
      well-designed investigations evaluating the role and feasibility of technological
      interventions (customized to each LMIC's locality) in clinical decision making
      for diabetes care.

PMID- 21722572
TI  - Pediatric diabetes registries: when baby steps are not enough.
AB  - Effective diabetes research relies on pattern recognition. Although information
      technology (IT) has been used to aid researchers in recognizing patterns, there
      are still barriers to effective data collection, analysis, and collaboration
      inherent in using outdated methods and technology designed to fulfill clinical,
      not research, purposes. This article discusses seven problems with current
      research and outlines a solution in which innovative IT can be harnessed to
      overcome each problem, resulting in better research outcomes. New IT solutions on
      the market, such as meta-registries, are designed specifically to handle the
      complex data collection and analysis problems associated with diabetes research.
      A meta-registry with an ontology automatically harmonizes data from disparate
      sources, allowing researchers to devote their time to pattern recognition. With
      all essential data centralized and harmonized, researchers are also provided with
      a more complete view of each patient or research subject. When researchers can
      view and report across all data types at the same time, they are able to discover
      patterns and associations that are indistinguishable using traditional
      methodologies. This capability proves extremely beneficial, particularly for
      multifactorial disease research such as diabetes research.

PMID- 21722573
TI  - Interstitial fluid physiology as it relates to glucose monitoring technologies:
      symposium introduction.
AB  - Nearly all commercially available glucose sensors share the subcutaneous
      interstitial fluid (ISF) compartment as their preferred implantation site.
      However, ISF physiology as it relates to glucose sensors is not well understood.
      This special symposium titled "Interstitial Fluid Physiology as It Relates to
      Glucose Monitoring Technologies" is intended to help to bridge the gap in our
      understanding. This symposium is intended to foster a greater understanding of
      biological factors that impact the success of implantable glucose monitors and to
      inspire additional research in the area of ISF physiology as it relates to
      glucose sensing. Recognition that sensor designers need to have an intimate
      understanding of the biological environment in which their sensor will reside is
      emphasized. The symposium is published in two parts, with part I published in
      September 2010 and part II published in May 2011. All articles published in this
      symposium are summarized herein.

PMID- 21722574
TI  - Metabolic biofouling of glucose sensors in vivo: role of tissue microhemorrhages.
AB  - OBJECTIVE: Based on our in vitro study that demonstrated the adverse effects of
      blood clots on glucose sensor function, we hypothesized that in vivo local tissue
      hemorrhages, induced as a consequence of sensor implantation or sensor movement
      post-implantation, are responsible for unreliable readings or an unexplained loss
      of functionality shortly after implantation. RESEARCH DESIGN AND METHODS: To
      investigate this issue, we utilized real-time continuous monitoring of blood
      glucose levels in a mouse model. Direct injection of blood at the tissue site of
      sensor implantation was utilized to mimic sensor-induced local tissue
      hemorrhages. RESULTS: It was found that blood injections, proximal to the sensor,
      consistently caused lowered sensor glucose readings, designated temporary signal
      reduction, in vivo in our mouse model, while injections of plasma or saline did
      not have this effect. CONCLUSION: These results support our hypothesis that
      tissue hemorrhage and resulting blood clots near the sensor can result in lowered
      local blood glucose concentrations due to metabolism of glucose by the clot. The
      lowered local blood glucose concentration led to low glucose readings from the
      still functioning sensor that did not reflect the systemic glucose level.

PMID- 21722575
TI  - Monitoring of glucose in brain, adipose tissue, and peripheral blood in patients
      with traumatic brain injury: a microdialysis study.
AB  - BACKGROUND: Episodes of hyperglycemia are considered to be a secondary insult in
      traumatically brain-injured patients and have been shown to be associated with
      impaired outcome. Intensive insulin therapy to maintain a strict glucose level
      has been suggested to decrease morbidity and mortality in critically ill patients
      but this aggressive insulin treatment has been challenged. One aspect of strict
      glucose control is the risk of developing hypoglycemia. Extracellular
      intracerebral hypoglycemia monitored by intracerebral microdialysis has been
      shown to correlate with poor outcome. Monitoring of blood glucose during
      neurointensive care is important because adequate glucose supply from the
      systemic circulation is crucial to maintain the brain's glucose demand after
      brain injury. This study investigates the correlation of glucose levels in
      peripheral blood, subcutaneous (SC) fat, and extracellular intracerebral tissue
      in patients with severe traumatic brain injury during neurointensive care.
      METHODS: In this study, we included 12 patients with severe traumatic brain
      injury. All patients received one microdialysis catheter each, with a membrane
      length of 10 mm (CMA 70, CMA Microdialysis AB) in the injured hemisphere of the
      brain and in the noninjured hemisphere of the brain. An additional microdialysis
      catheter with a membrane length of 30 mm (CMA 60, CMA Microdialysis AB) was
      placed in the periumbilical subcutaneous adipose tissue. We studied the
      correlation among levels of glucose measured in peripheral blood, adipose tissue,
      and the noninjured hemisphere of the brain during the first 12 hours and during 3
      consecutive days in neurointensive care. RESULTS: We found a significant positive
      correlation between levels of glucose in peripheral blood, SC fat, and the
      noninjured brain during the initial 12 hours but not in injured brain. However,
      the result varied between the patients during the 3-day measurements. In 7
      patients, there was a significant positive correlation between glucose in blood
      and noninjured brain, while in 4 patients this correlation was poor. In 4
      patients, there was a significant positive correlation in injured brain and
      blood. Furthermore, there was a significant correlation between brain and adipose
      tissue glucose during the 3-day measurements in 11 out of 12 patients.
      CONCLUSION: This study indicates that there is a good correlation between blood
      glucose and adipose tissue during initial and later time points in the
      neurointensive care unit whereas the correlation between blood and brain seems to
      be more individualized among patients. This emphasizes the importance of using
      intracerebral microdialysis to ensure adequate intracerebral levels of glucose in
      patients suffering from severe traumatic brain injury and to detect hypoglycemia
      in the brain despite normal levels of blood glucose.

PMID- 21722576
TI  - Implant healing in experimental animal models of diabetes.
AB  - Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally,
      there is an increasing number of patients receiving implantable devices such as
      glucose sensors and orthopedic implants. Thus, it is likely that the number of
      diabetic patients receiving these devices will also increase. Even though
      implantable medical devices are considered biocompatible by the Food and Drug
      Administration, the adverse tissue healing that occurs adjacent to these foreign
      objects is a leading cause of their failure. This foreign body response leads to
      fibrosis, encapsulation of the device, and a reduction or cessation of device
      performance. A second adverse event is microbial infection of implanted devices,
      which can lead to persistent local and systemic infections and also exacerbates
      the fibrotic response. Nearly half of all nosocomial infections are associated
      with the presence of an indwelling medical device. Events associated with both
      the foreign body response and implant infection can necessitate device removal
      and may lead to amputation, which is associated with significant morbidity and
      cost. Diabetes mellitus is generally indicated as a risk factor for the infection
      of a variety of implants such as prosthetic joints, pacemakers, implantable
      cardioverter defibrillators, penile implants, and urinary catheters. Implant
      infection rates in diabetic patients vary depending upon the implant and the
      microorganism, however, for example, diabetes was found to be a significant
      variable associated with a nearly 7.2% infection rate for implantable
      cardioverter defibrillators by the microorganism Candida albicans. While research
      has elucidated many of the altered mechanisms of diabetic cutaneous wound
      healing, the internal healing adjacent to indwelling medical devices in a
      diabetic model has rarely been studied. Understanding this healing process is
      crucial to facilitating improved device design. The purpose of this article is to
      summarize the physiologic factors that influence wound healing and infection in
      diabetic patients, to review research concerning diabetes and biomedical implants
      and device infection, and to critically analyze which diabetic animal model might
      be advantageous for assessing internal healing adjacent to implanted devices.

PMID- 21722577
TI  - Modulation of the foreign body reaction for implants in the subcutaneous space:
      microdialysis probes as localized drug delivery/sampling devices.
AB  - Modulation of the foreign body reaction is considered to be an important step
      toward creation of implanted sensors with reliable long-term performance. In this
      work, microdialysis probes were implanted into the subcutaneous space of Sprague
      Dawley rats. The probe performance was evaluated by comparing collected
      endogenous glucose concentrations with internal standard calibration (2
      deoxyglucose, antipyrine, and vitamin B12). Probes were tested until failure,
      which for this work was defined as loss of fluid flow. In order to determine the
      effect of fibrous capsule formation on probe function, monocyte chemoattractant
      protein-1/CC chemokine ligand 2 (MCP-1/CCL2) was delivered locally via the probe
      to increase capsule thickness and dexamethasone 21-phosphate was delivered to
      reduce capsule thickness. Probes delivering MCP-1 had a capsule that was twice
      the thickness (500-600 MUm) of control probes (200-225 MUm) and typically failed
      2 days earlier than control probes. Probes delivering dexamethasone 21-phosphate
      had more fragile capsules and the probes typically failed 2 days later than
      controls. Unexpectedly, extraction efficiency and collected glucose
      concentrations exhibited minor differences between groups. This is an interesting
      result in that the foreign body capsule formation was related to the duration of
      probe function but did not consistently relate to probe calibration.

PMID- 21722578
TI  - Biomechanics of the sensor-tissue interface-effects of motion, pressure, and
      design on sensor performance and the foreign body response-part I: theoretical
      framework.
AB  - The importance of biomechanics in glucose sensor function has been largely
      overlooked. This article is the first part of a two-part review in which we look
      beyond commonly recognized chemical biocompatibility to explore the biomechanics
      of the sensor-tissue interface as an important aspect of continuous glucose
      sensor biocompatibility. Part I provides a theoretical framework to describe how
      biomechanical factors such as motion and pressure (typically micromotion and
      micropressure) give rise to interfacial stresses, which affect tissue physiology
      around a sensor and, in turn, impact sensor performance. Three main contributors
      to sensor motion and pressure are explored: applied forces, sensor design, and
      subject/patient considerations. We describe how acute forces can temporarily
      impact sensor signal and how chronic forces can alter the foreign body response
      and inflammation around an implanted sensor, and thus impact sensor performance.
      The importance of sensor design (e.g., size, shape, modulus, texture) and
      specific implant location on the tissue response are also explored. In Part II:
      Examples and Application (a sister publication), examples from the literature are
      reviewed, and the application of biomechanical concepts to sensor design are
      described. We believe that adding biomechanical strategies to the arsenal of
      material compositions, surface modifications, drug elution, and other chemical
      strategies will lead to improvements in sensor biocompatibility and performance.

PMID- 21722579
TI  - Biomechanics of the sensor-tissue interface-effects of motion, pressure, and
      design on sensor performance and foreign body response-part II: examples and
      application.
AB  - This article is the second part of a two-part review in which we explore the
      biomechanics of the sensor-tissue interface as an important aspect of continuous
      glucose sensor biocompatibility. Part I, featured in this issue of Journal of
      Diabetes Science and Technology, describes a theoretical framework of how
      biomechanical factors such as motion and pressure (typically micromotion and
      micropressure) affect tissue physiology around a sensor and in turn, impact
      sensor performance. Here in Part II, a literature review is presented that
      summarizes examples of motion or pressure affecting sensor performance. Data are
      presented that show how both acute and chronic forces can impact continuous
      glucose monitor signals. Also presented are potential strategies for countering
      the ill effects of motion and pressure on glucose sensors. Improved engineering
      and optimized chemical biocompatibility have advanced sensor design and function,
      but we believe that mechanical biocompatibility, a rarely considered factor, must
      also be optimized in order to achieve an accurate, long-term, implantable sensor.

PMID- 21722580
TI  - The effect of type-2-diabetes-related vascular endothelial dysfunction on skin
      physiology and activities of daily living.
AB  - A common factor contributing to organ damage in type 2 diabetes mellitus (T2DM)
      is impaired tissue blood flow caused by damage to vascular endothelial cells
      (VECs). Damage can occur even before the clinical diagnosis of diabetes. It can
      be caused by both a high average blood glucose concentration and/or large daily
      spikes in blood glucose. While much of the present literature focuses on the
      damage to VECs and organs from these large glucose excursions, this review will
      focus on the consequence of this damage, that is, how endothelial cell damage in
      diabetes affects normal daily activities (e.g., exercise, reaction to typical
      stimuli) and various treatment modalities (e.g.. contrast baths and electrical
      stimulation therapy). It is important to understand the effects of VEC damage
      such as poor skin blood flow, compromised thermoregulation, and altered response
      to skin pressure in designing diabetes technologies as simple as heating pads and
      as complex as continuous glucose monitors. At the simplest level, people with
      diabetes have poor circulation to the skin and other organs. In the skin, even
      the blood flow response to locally applied pressure, such as during standing, is
      different than for people who do not have T2DM. Simple weight bearing on the foot
      can occlude the skin circulation. This makes the skin more susceptible to damage.
      In addition, endothelial damage has far-reaching effects on the whole body during
      normal activities of daily living, including an impaired response to local heat,
      such as hot packs and contrast baths, and higher body temperatures during whole
      body heating due to impaired blood flow and a reduced ability to sweat. Finally,
      because of multiple organ damage, people with T2DM have poor balance and gait and
      impaired exercise performance.

PMID- 21722581
TI  - The effect of real-time continuous glucose monitoring on glycemic control in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Real-time continuous glucose monitoring (RT-CGM) improves hemoglobin
      A1c (A1C) and hypoglycemia in people with type 1 diabetes mellitus and those with
      type 2 diabetes mellitus (T2DM) on prandial insulin; however, it has not been
      tested in people with T2DM not taking prandial insulin. We evaluated the utility
      of RT-CGM in people with T2DM on a variety of treatment modalities except
      prandial insulin. METHODS: We conducted a prospective, 52-week, two-arm,
      randomized trial comparing RT-CGM (n = 50) versus self-monitoring of blood
      glucose (SMBG) (n = 50) in people with T2DM not taking prandial insulin. Real
      time continuous glucose monitoring was used for four 2-week cycles (2 weeks on/1
      week off). All patients were managed by their usual provider. This article
      reports on changes in A1C 0-12 weeks. RESULTS: Mean (+/- standard deviation)
      decline in A1C at 12 weeks was 1.0% (+/- 1.1%) in the RT-CGM group and 0.5% (+/-
      0.8%) in the SMBG group (p = .006). There were no group differences in the net
      change in number or dosage of hypoglycemic medications. Those who used the RT-CGM
      for >= 48 days (per protocol) reduced their A1C by 1.2% (+/- 1.1%) versus 0.6%
      (+/- 1.1%) in those who used it <48 days (p = .003). Multiple regression analyses
      statistically adjusting for baseline A1C, an indicator for usage, and known
      confounders confirmed the observed differences between treatment groups were
      robust (p = .009). There was no improvement in weight or blood pressure.
      CONCLUSIONS: Real-time continuous glucose monitoring significantly improves A1C
      compared with SMBG in patients with T2DM not taking prandial insulin. This
      technology might benefit a wider population of people with diabetes than
      previously thought.

PMID- 21722582
TI  - Benefits of blinded continuous glucose monitoring during a randomized clinical
      trial.
AB  - BACKGROUND: Real-time, personal continuous glucose monitoring (CGM) is a
      validated technology that can help patients improve glycemic control. Blinded CGM
      is a promising technology for obtaining retrospective data in clinical research
      where the quantity and quality of blood glucose information is important. This
      study was designed to investigate the use of novel procedures to enhance data
      capture from blinded CGM. METHODS: Following a 4-week run-in, 46 patients with
      type 1 diabetes were randomized to one of two prandial insulins for a 12-week
      treatment period, after which they were crossed over to the alternate treatment
      for 12 weeks. Continuous glucose monitoring was implemented at the end of run-in
      (practice only) and during the last 2 weeks of each treatment period. Eighty
      percent of 288 possible daily glucose values were required for at least three
      days. Continuous glucose monitoring was extended for an additional week if these
      criteria were not met, and patients were allowed to insert sensors at home when
      necessary. Continuous glucose monitoring results were compared to reference eight
      point self-monitoring of blood glucose (SMBG). RESULTS: Higher than expected
      sensor failure rate was approximately 25%. During run-in, 12 of 45 attempted
      profiles failed adequacy criteria. However, treatment periods had only 1 of 82
      attempted profiles considered inadequate (6 cases required an additional week of
      CGM). Using SMBG as reference, 93.7% of 777 CGM values were in Clarke error grid
      zones A+B. CONCLUSIONS: With appropriate training, adequate practice, and
      opportunity to repeat blinded CGM as needed, nearly 100% of attempted profiles
      can be obtained successfully.

PMID- 21722583
TI  - Reduction of postprandial glycemic excursions in patients with type 1 diabetes: a
      novel human insulin formulation versus a rapid-acting insulin analog and regular
      human insulin.
AB  - BACKGROUND: Evaluation of postprandial glycemic excursions in patients with type
      1 diabetes with three prandial insulins: VIAjectTM (LinjetaTM), an ultra-fast
      insulin (UFI); insulin lispro (LIS); and regular human insulin (RHI). METHODS:
      After stabilization of preprandial glycemia, 18 patients received a subcutaneous
      injection with an individualized insulin dose prior to a meal. RESULTS: Injection
      of UFI resulted in a more rapid insulin absorption than with either LIS or RHI
      (time to half-maximal insulin levels: 13.1 +/- 5.2 vs 25.4 +/- 7.6 and 38.4 +/-
      19.5 min; p = .001 vs LIS and p < .001 vs RHI, LIS vs. RHI p < .001). Maximal
      postprandial glycemia was lower with UFI (0-180 min; 157 +/- 30 mg/dl; p = .002
      vs RHI) and LIS (170 +/- 42 mg/dl; p = .668 vs RHI) than after RHI (191 +/- 46
      mg/dl; RHI vs LIS p = .008). The difference between maximum and minimum glycemia
      was smaller with UFI (70 +/- 17 mg/dl) than with either RHI (91 +/- 33 mg/dl; p =
      .007 vs UFI) or LIS (89 +/- 18 mg/dl; p = .011 vs UFI). Also, the area under the
      blood glucose profile was lower with UFI than with RHI (0-180 min; 21.8 +/- 5.8
      vs 28.4 +/- 7.6 g.min/dl; p < .001). CONCLUSIONS: The rapid absorption of UFI
      results in a reduction of postprandial glycemic excursions.

PMID- 21722584
TI  - Use of a novel fluorescent glucose sensor in volunteer subjects with type 1
      diabetes mellitus.
AB  - BACKGROUND: Stress hyperglycemia in the critically ill has been found to be
      associated with increased morbidity and mortality. Studies have found significant
      improvements in morbidity and mortality in postsurgical patients whose glucose
      levels were closely maintained in the euglycemic range. However, subsequent
      studies, in particular the Normoglycemia in Intensive Care Evaluation and
      Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study, found no
      improvement in subjects with tight glycemic control. In addition to differences
      in protocol design, patients in the tight glycemic control arm of the NICE-SUGAR
      study experienced high rates of hypoglycemia compared with other studies. One
      interpretation of the NICE-SUGAR study results is that it is difficult to achieve
      normal glycemia in critically ill patients with existing glucose monitoring
      technology. The purpose of the study reported here was to evaluate the safety and
      performance of a continuous intravascular glucose sensor that could be used in
      the future in critically ill patients. METHODS: A first-generation prototype of
      an intravascular continuous glucose sensor was evaluated in 29 volunteer subjects
      with type 1 diabetes mellitus. The sensor operates on the principle of quenched
      fluorescence. The fluorescent emission from the sensor chemistry is nonlinear,
      resulting in improved accuracy in the hypoglycemic range. The duration of each
      study was 8 hours. Sensor output was compared with temporally correlated
      reference measurements made from venous samples on a laboratory glucose analyzer.
      RESULTS: Data were obtained from 18 of the 29 subjects in the study. Data were
      analyzed retrospectively using a factory calibration plus a one-point in vivo
      calibration. The mean absolute relative difference was 7.97%, and 95.1% of all
      the points were in zone A of the Clarke error grid. CONCLUSIONS: This pilot study
      was the first use in human subjects of a prototype of the GluCath Intravascular
      Continuous Glucose Monitoring System (GluCath System). The GluCath System is
      based on a novel fluorescent sensor chemistry. The study found the GluCath System
      had a high level of accuracy as compared with a laboratory reference analyzer.

PMID- 21722585
TI  - Data processing for noninvasive continuous glucose monitoring with a multisensor
      device.
AB  - BACKGROUND: Impedance spectroscopy has been shown to be a candidate for
      noninvasive continuous glucose monitoring in humans. However, in addition to
      glucose, other factors also have effects on impedance characteristics of the skin
      and underlying tissue. METHOD: Impedance spectra were summarized through a
      principal component analysis and relevant variables were identified with Akaike's
      information criterion. In order to model blood glucose, a linear least-squares
      model was used. A Monte Carlo simulation was applied to examine the effects of
      personalizing models. RESULTS: The principal component analysis was able to
      identify two major effects in the impedance spectra: a blood glucose-related
      process and an equilibration process related to moisturization of the skin and
      underlying tissue. With a global linear least-squares model, a coefficient of
      determination (R2) of 0.60 was achieved, whereas the personalized model reached
      an R2 of 0.71. The Monte Carlo simulation proved a significant advantage of
      personalized models over global models. CONCLUSION: A principal component
      analysis is useful for extracting glucose-related effects in the impedance
      spectra of human skin. A linear global model based on Solianis Multisensor data
      yields a good predictive power for blood glucose estimation. However, a
      personalized linear model still has greater predictive power.

PMID- 21722586
TI  - Glycated albumin modulates endothelial cell thrombogenic and inflammatory
      responses.
AB  - BACKGROUND: It has become established that a diabetic vasculature promotes
      cardiovascular disease progression via changes to endothelial cells, platelets,
      and the interactions of these cells. It is believed that the majority of these
      changes are induced by the presence of advanced glycation end products (AGEs),
      which permanently alter various functions. Studies have shown that platelets
      perpetuate endothelial cell responses under these conditions. However, the role
      of changes in endothelial cell thrombogenicity and inflammatory responses, after
      subjected to AGEs, has not been characterized. Our objective was to evaluate the
      effects of AGEs on these functions. METHODS: To accomplish this, albumin was
      chemically modified by exposure to glucose for up to 8 weeks, and endothelial
      cells were subjected to glycated albumin for up to 5 days in a cell culture
      system. A time course for changes in endothelial cell viability, density,
      morphology, and metabolic activity were investigated, along with the surface
      expression of intercellular adhesion molecule-1, thrombomodulin, tissue factor,
      connexin-43, and caveolin-1. RESULTS: Endothelial cells exposed to irreversibly
      glycated albumin were less viable, proliferated slower, and had a lower metabolic
      activity as compared to cells exposed to nonglycated albumin. Endothelial cells
      that were exposed to any glycated albumin were procoagulant and proinflammatory
      as compared with all other conditions. There were no overall trends in the
      expression of connexin-43 or caveolin-1. CONCLUSIONS: Our data suggest that the
      presence of irreversible glycated albumin is deleterious to endothelial cells,
      makes endothelial cells more procoagulant, and promotes inflammatory responses.
      It is therefore possible that endothelial cell activation may precede and promote
      platelet activation during diabetic conditions.

PMID- 21722587
TI  - Quality of life and objective measures of diabetic neuropathy in a prospective
      placebo-controlled trial of ruboxistaurin and topiramate.
AB  - BACKGROUND: The Norfolk Quality of Life Questionnaire-Diabetic Neuropathy
      (Norfolk QOL-DN) is a validated comprehensive questionnaire designed to capture
      the entire spectrum of DN related to large fiber, small fiber, and autonomic
      neuropathy not captured in existing instruments. We aimed to determine if the
      Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve
      fiber-specific objective measures in a placebo-controlled trial of two agents
      that affect different nerve fibers. METHODS: Sixty patients with DN were
      allocated to treatment on ruboxistaurin (RBX) (n = 18), topiramate (TPX) (n =
      18), or placebo (n = 18). QOL-DN was administered and objective measures of nerve
      function were performed at entry and end of the study period. RESULTS: Total QOL
      scores improved significantly in the active treatment groups (RBX -9.56 +/- 4.13;
      TPX -12.22 +/- 2.76) but not in placebo (-5.56 +/- 3.49). There were differences
      in nerve function improvement between treatments. Neurological symptom scores
      (NSS) improved with TPX from 5.5 (2.3) to 4.3 (0.65) (p = .007), sensory scores
      improved with TPX from 15.5 (1.79) to 8.3 (1.19) (p < .001), motor scores did not
      change, and sensory and motor impairment scores improved with TPX from 18.8
      (2.15) to 12.1 (1.71) (p = .003). Total neuropathy scores (TNS) improved with TPX
      from 24.35 (2.61) to 16.35 (2.02) (p = .001). Neuropathy total symptom score-6
      (NTSS-6) changes were significant for both treatments: RBX 4.38 (0.75) to 1.49
      (0.38) (p < .001) and TPX 7.57 (1.3) to 4.26 (0.95) (p = .036). Changes in QOL-DN
      large fiber subscores correlated (Spearman's rank) significantly with changes in
      NTSS-6 (r = 0.55; p < .0001), NSS (r = 0.31; p < .04), neuropathy impairment
      score (NIS) (r = 0.35; p < .02), and TNS (r = 0.48; p < .0006). Changes in QOL-DN
      small fiber subscores correlated significantly with changes in NTSS-6 total
      scores (r = 0.40; p < .005) and intraepidermal nerve fiber density (IENFD) (r = 
      0.29; p < .05). CONCLUSION: Ruboxistaurin produced significant improvement in
      large fiber measures while TPX produced significant changes in small fiber
      measures. The Norfolk QOL-DN tool differentiated between these changes captured
      in the fiber-specific domains. Correlations were found between objective measures
      of neuropathy and total QOL, but those with nerve fiber domain scores were modest
      and reinforce the need to quantify QOL as an endpoint in neuropathy independent
      of other measures.

PMID- 21722588
TI  - Patient understanding of diabetes self-management: participatory decision-making
      in diabetes care.
AB  - OBJECTIVE: Our aim was to determine whether patient participation in decision
      making about diabetes care is associated with understanding of diabetes self
      management and subsequent self-care practices. We also identified issues that
      would impact messaging for use in mobile diabetes communication. RESEARCH DESIGN
      AND METHODS: A cross-sectional observational study was conducted with type 2
      diabetes patients (n = 81) receiving their care at the University of Maryland
      Joslin Diabetes Center. A convenience sample of patients were eligible to
      participate if they were aged 25-85 years, had type 2 diabetes, spoke English,
      and visited their physician diabetes manager within the past 6 months. In-person
      patient interviews were conducted at the time of clinic visits to assess patient
      understanding of diabetes management, self-care practices, and perceptions of
      participation in decision-making about diabetes care. RESULTS: African Americans
      reported fewer opportunities to participate in decision-making than Caucasians,
      after controlling for education [mean difference (MD) = -2.4, p = .02]. This
      association became insignificant after controlling for patient-physician race
      concordance (MD = -1.5, p = .21). Patient understanding of self-care was
      predicted by having greater than high school education (MD = 3.6, p = .001) and
      having physicians who involved them in decision-making about their care. For each
      unit increase in understanding of diabetes self-care, the mean patient self-care
      practice score increased by 0.16 (p = .003), after adjustment for patient race
      and education. CONCLUSIONS: Patient participation in decision-making is
      associated with better understanding of care. Participation in decision-making
      plays a key role in patient understanding of diabetes self-management and
      subsequent self-care practices. Patients with limited education need specific
      instruction in foot care, food choices, and monitoring hemoglobin A1c.

PMID- 21722589
TI  - Effect of diabetes mellitus on outcomes of hyperglycemia in a mixed medical
      surgical intensive care unit.
AB  - BACKGROUND: Intensive insulin therapy and degree of glycemic control in
      critically ill patients remains controversial, particularly in patients with
      diabetes mellitus. We hypothesized that diabetic patients who achieved tight
      glucose control with continuous insulin therapy would have less morbidity and
      lower mortality than diabetic patients with uncontrolled blood glucose. METHOD: A
      retrospective chart review was performed on 395 intensive care unit (ICU)
      patients that included 235 diabetic patients. All patients received an
      intravenous insulin protocol targeted to a blood glucose (BG) level of 80-140
      mg/dl. Outcomes were compared between (a) nondiabetic and diabetic patients, (b)
      diabetic patients with controlled BG levels (80-140 mg/dl) versus uncontrolled
      levels (>140 mg/dl), and (c) diabetic survivors and nonsurvivors. RESULTS:
      Diabetic patients had a shorter ICU stay compared to nondiabetic patients (10 +/-
      0.7 vs 13 +/- 1.1, p = .01). The mean BG of the diabetic patients was 25% higher
      on average in the uncontrolled group than in the controlled (166 +/- 26 vs 130 +/
      9.4 mg/dl, p < .01). There was no difference in ICU and hospital length of stay
      (LOS) between diabetic patients who were well controlled compared to those who
      were uncontrolled. Diabetic nonsurvivors had a significantly higher incidence of
      hypoglycemia (BG <60 mg/dl) compared to diabetic survivors. CONCLUSION: The
      results showed that a diagnosis of diabetes was not an independent predictor of
      mortality, and that diabetic patients who were uncontrolled did not have worse
      outcomes. Diabetic nonsurvivors were associated with a greater amount of
      hypoglycemic episodes, suggesting these patients may benefit from a more lenient
      blood glucose protocol.

PMID- 21722590
TI  - Biosimilar insulins: how similar is similar?
AB  - Biosimilar insulins (BIs) are viewed as commercially attractive products by a
      number of companies. In order to obtain approval in the European Union or the
      United States, where there is not a single BI currently on the market, a
      manufacturer needs to demonstrate that a given BI has a safety and efficacy
      profile that is similar to that of the "original" insulin formulation that is
      already on the market. As trivial as this may appear at first glance, it is not
      trivial at all for a good number of reasons that will be discussed in this
      commentary. As with protein manufacturing, modifications in the structure of the
      insulin molecule can take place (which can have serious consequences for the
      biological effects induced), so a rigid and careful assessment is absolutely
      necessary. The example of Marvel's failed application with the European Medicines
      Agency provides insights into the regulatory and clinical challenges surrounding
      the matter of BI. Although a challenging BI approval process might be regarded as
      a hurdle to keep companies out of certain markets, it is fair to say that the
      potential safety and efficacy issues surrounding BI are substantial and relevant
      and do warrant a careful and evidence-driven approval process.

PMID- 21722591
TI  - Intensive insulin therapy in critically ill hospitalized patients: making it safe
      and effective.
AB  - Intensive insulin therapy (IIT) for hyperglycemia in critically ill patients has
      become a standard practice. Target levels for glycemia have fluctuated since
      2000, as evidence initially indicated that tight glycemic control to so-called
      normoglycemia (80-110 mg/dl) leads to the lowest morbidity and mortality without
      hypoglycemic complications. Subsequent studies have demonstrated minimal clinical
      benefit combined with greater hypoglycemic morbidity and mortality with tight
      glycemic control in this population. The consensus glycemic targets were then
      liberalized to the mid 100s (mg/dl). Handheld POC blood glucose (BG) monitors
      have migrated from the outpatient setting to the hospital environment because
      they save time and money for managing critically ill patients who require IIT.
      These devices are less accurate than hospital-grade POC blood analyzers or
      central laboratory analyzers. Three questions must be answered to understand the
      role of IIT for defined populations of critically ill patients: (1) How safe is
      IIT, with various glycemic targets, from the risk of hypoglycemia? (2) How
      tightly must BG be controlled for this approach to be effective? (3) What role
      does the accuracy of BG measurements play in affecting the safety of this method?
      For each state of impaired glucose regulation seen in the hospital, such as
      hyperglycemia, hypoglycemia, or glucose variability, the benefits, risks, and
      goals of treatment, including IIT, might differ. With improved accuracy of BG
      monitors, IIT might be rendered even more intensive than at present, because
      patients will be less likely to receive inadvertent overdosages of insulin.
      Greater doses of insulin, but with dosing based on more accurate glucose levels,
      might result in less hypoglycemia, less hyperglycemia, and less glycemic
      variability.

PMID- 21722592
TI  - Telemedicine security: a systematic review.
AB  - Telemedicine is a technology-based alternative to traditional health care
      delivery. However, poor security measures in telemedicine services can have an
      adverse impact on the quality of care provided, regardless of the chronic
      condition being studied. We undertook a systematic review of 58 journal articles
      pertaining to telemedicine security. These articles were selected based on a
      keyword search on 14 relevant journals. The articles were coded to evaluate the
      methodology and to identify the key areas of research in security that are being
      reviewed. Seventy-six percent of the articles defined the security problem they
      were addressing, and only 47% formulated a research question pertaining to
      security. Sixty-one percent proposed a solution, and 20% of these tested the
      security solutions that they proposed. Prior research indicates inadequate
      reporting of methodology in telemedicine research. We found that to be true for
      security research as well. We also identified other issues such as using outdated
      security standards.

PMID- 21722593
TI  - The scope of cell phones in diabetes management in developing country health care
      settings.
AB  - Diabetes has emerged as a major public health concern in developing nations.
      Health systems in most developing countries are yet to integrate effective
      prevention and control programs for diabetes into routine health care services.
      Given the inadequate human resources and underfunctioning health systems, we need
      novel and innovative approaches to combat diabetes in developing-country
      settings. In this regard, the tremendous advances in telecommunication
      technology, particularly cell phones, can be harnessed to improve diabetes care.
      Cell phones could serve as a tool for collecting information on surveillance,
      service delivery, evidence-based care, management, and supply systems pertaining
      to diabetes from primary care settings in addition to providing health messages
      as part of diabetes education. As a screening/diagnostic tool for diabetes, cell
      phones can aid the health workers in undertaking screening and diagnostic and
      follow-up care for diabetes in the community. Cell phones are also capable of
      acting as a vehicle for continuing medical education; a decision support system
      for evidence-based management; and a tool for patient education, self-management,
      and compliance. However, for widespread use, we need robust evaluations of cell
      phone applications in existing practices and appropriate interventions in
      diabetes.

PMID- 21722594
TI  - Elevated intact proinsulin levels are indicative of Beta-cell dysfunction,
      insulin resistance, and cardiovascular risk: impact of the antidiabetic agent
      pioglitazone.
AB  - BACKGROUND: Insulin resistance (IR) and deterioration of beta-cell secretion are
      main features in the development of type 2 diabetes, which is reflected in
      increasing serum intact proinsulin levels in later disease stage. Introduction of
      stable assays that are able to distinguish between intact proinsulin and its
      specific and unspecific cleavage products has resulted in the finding that serum
      intact proinsulin values can serve as a direct marker for beta-cell dysfunction,
      are a highly specific indicator of IR, and can predict cardiovascular risk.
      METHOD: Determination of fasting intact proinsulin may be used to monitor and
      optimize antidiabetic therapeutic approaches. Our study group has been involved
      in a variety of clinical studies investigating drug effects on beta-cell
      secretory capacity, IR, and intact proinsulin levels. One focus was on the impact
      of insulin-sensitizing therapy with pioglitazone on the pancreatic beta-cell
      load. RESULTS: Treatment with pioglitazone resulted in significant decreases in
      elevated proinsulin levels in type 2 diabetes patients. This effect was
      independent from glycemic control. CONCLUSIONS: Measurement of fasting intact
      proinsulin values allows a staging of beta-cell dysfunction and evaluation of IR,
      thus providing an interesting diagnostic tool for both selection of appropriate
      therapy and monitoring of treatment success.

PMID- 21722595
TI  - DIAMAP: a road map for diabetes research in Europe.
AB  - The DIAMAP Project, which has drawn up a road map for diabetes research in
      Europe, has now concluded, and the results are available in the form of a report
      and searchable databases. The DIAMAP road maps provide strategic guidance for
      diabetes research activity and investment in Europe, with the person with
      diabetes and a broad approach to research being integral to the process.

PMID- 21722596
TI  - Self-management support interventions that are clinically linked and technology
      enabled: can they successfully prevent and treat diabetes?
AB  - Patients with diabetes need a complex set of services and supports. The challenge
      of integrating these services into the diabetes regimen can be successfully
      overcome through self-management support interventions that are clinically linked
      and technology enabled: self-management support because patients need help
      mastering the knowledge, attitudes, skills, and behaviors so necessary for good
      outcomes; interventions because comprehensive theory-based, evidence-proven, long
      term, longitudinal interventions work better than direct-to-consumer or
      nonplanned health promotion approaches; clinically linked because patients are
      more likely to adopt new behaviors when the approach is in the context of a
      trusted therapeutic relationship and within an effective medical care system; and
      technology enabled because capitalizing on the amazing power of information
      technology leads to the delivery of cost-effective, scalable, engaging solutions
      that prevent and manage diabetes.

PMID- 21722597
TI  - Innovations in technology for the treatment of diabetes: clinical development of
      the artificial pancreas (an autonomous system).
AB  - The Food and Drug Administration in collaboration with the National Institutes of
      Health presented a public workshop to facilitate medical device innovation in the
      development of the artificial pancreas (or autonomous system) for the treatment
      of diabetes mellitus on November 10, 2010 in Gaithersburg, Maryland. The purpose
      of the workshop was to discuss four aspects of artificial pancreas research and
      development, including: (1) the current state of device systems for autonomous
      systems for the treatment of diabetes mellitus; (2) challenges in developing this
      expert device system using existing technology; (3) clinical expectations for
      these systems; and (4) development plans for the transition of this device system
      toward an outpatient setting. The patients discussed how clinical science, system
      components, and regulatory policies will all need to harmonize in order to
      achieve the goal of seeing an AP product brought forward to the marketplace for
      patients to use.

PMID- 21722598
TI  - Comparison of the Freestyle LiteTM blood glucose monitoring system to the yellow
      springs instruments glucose oxidase analyzer for use during glucose clamp studies
      in nondiabetic subjects undergoing magnetic resonance imaging.

PMID- 21722599
TI  - De novo once-monthly darbepoetin alpha treatment for the anemia of chronic kidney
      disease using a computerized algorithmic approach.
AB  - BACKGROUND: Anemia of chronic kidney disease (CKD) has been traditionally treated
      by erythropoiesis-stimulating agents (ESAs) and/or iron following manual
      determination of dose. We hypothesized that once-monthly (QM) algorithmically
      dosed darbepoetin alpha (DA) and iron administration would successfully treat
      anemia of CKD in ESA-naive CKD subjects. METHODS: QM DA and iron doses were
      determined via a computerized program targeting a hemoglobin (Hb) of 10.5 - 12.5
      g/dl in anemic, ESA-naive, CKD Stages 3 - 5 subjects. Six consecutive QM doses
      were administered. Hb, ferritin, and transferrin saturation were recorded. Data
      are presented as means +/- standard deviation. RESULTS: Anemia was identified in
      133 subjects, with a mean follow-up of 188 days. DA doses and Hb were
      significantly greater at Months 3 and 6 compared to baseline (p < 0.05); DA doses
      were 109 +/- 68 MUg and 118 +/- 91, respectively, at Months 3 and 6. Hemoglobin
      levels were correspondingly 11.3 +/- 1.1 g/dl and 11.3 +/- 1.0. 78% of patients
      achieved the target Hb by 6 months of therapy. The elevation of Hb was greater in
      non-proteinuric than proteinuric subjects at 6 months of treatment (11.6 +/- 0.8
      g/dl vs. 11.0 +/- 1.1; p < 0.05), despite lower DA dose (96 +/- 76 MUg vs. 139 +/
      98; p < 0.05). CONCLUSION: Successful treatment of the anemia of CKD by QM DA
      based upon a computerized dosing program was achieved by 6 months in 78% of ESA
      naive, CKD subjects.

PMID- 21722600
TI  - Fewer dose changes with once-monthly C.E.R.A. in patients with chronic kidney
      disease.
AB  - BACKGROUND: Frequent dosing and requirements for dose adjustments of
      erythropoiesis-stimulating agents (ESAs) create significant burdens for
      healthcare providers and have been associated with hemoglobin (Hb) cycling,
      hampering maintenance of target Hb levels. We compared the frequency of dose
      changes in dialysis patients who received methoxy polyethylene glycolepoetin
      beta; (a continuous erythropoietin receptor activator (C.E.R.A.)) or a shorter
      acting ESA. METHODS: Data were analyzed from three Phase III maintenance trials,
      using almost identical protocols, in dialysis patients treated with C.E.R.A.
      every 2 weeks (q2w) or every 4 weeks (q4w) or a comparator ESA (epoetin or
      darbepoetin alpha; at their previous dose/administration interval). Dosage was
      adjusted to maintain Hb +/- 1 g/dl of baseline and 10 - 13.5 g/dl during
      titration (28 weeks) and evaluation (8 weeks), and 11 - 13 g/dl during follow-up
      (16 weeks). RESULTS: Data were analyzed from 564 patients treated with C.E.R.A.
      q2w, 410 with C.E.R.A. q4w and 572 with comparator ESA at their usual dosing
      interval. Significantly fewer dose changes were needed in patients receiving
      C.E.R.A. q2w (p < 0.05) or C.E.R.A. q4w (p < 0.001) than in patients treated with
      comparator ESAs. CONCLUSION: This retrospective analysis suggests that C.E.R.A.
      q4w maintains Hb levels in dialysis patients and requires fewer dose changes
      compared with other ESAs.

PMID- 21722601
TI  - Measurements on the routine chest radiograph as prognostic markers in Chinese
      peritoneal dialysis patients.
AB  - BACKGROUND: Fluid overload is a common problem in peritoneal dialysis (PD)
      patients. Cardiothoracic ratio (CTR) and vascular pedicle width (VPW) in routine
      chest radiograph are useful indicators of intravascular volume status and may
      represent important prognostic factors of PD patients. METHODS: We measured VPW
      and CTR in 286 unselected prevalent PD patients. VPW was further adjusted for the
      thoracic diameter (VPWR). One-year actuarial survival, technique survival, and
      duration of hospitalization were analyzed. RESULTS: The mean values of VPW, CTR,
      VPWR were 47.31 +/- 4.73 mm, 0.542 +/- 0.074, 0.170 +/- 0.024, respectively. VPW
      correlated with age (r = 0.143; p = 0.016), body weight (r = 0.371; p < 0.001),
      body height (r = 0.271; p < 0.001), and Charlson's index score (r = 0.153; p =
      0.01). One-year patient survival was 87.8%, and technique survival was 82.2%.
      None of the radiological measurements had an independent effect on one-year
      actuarial or technique survival by multivariate analysis. Both CTR and VPWR
      correlated with the duration of hospitalization (r = 0.192 and 0.186,
      respectively (p = 0.001 and 0.002). Multivariate regression analysis by log
      linear modeling showed that independent predictors of one-year hospitalization
      were VPWR, serum albumin, and SGA overall score. CONCLUSIONS: In Chinese PD
      patients, VPW was significantly correlated with age, body weight, body height and
      Charlson's index score. VPWR was an independent predictor of the duration of
      hospitalization. Further studies are needed to confirm the prognostic value of
      these radiographic measurements in PD patients.

PMID- 21722602
TI  - Saliva urea dipstick test: application in chronic kidney disease.
AB  - BACKGROUND: A noninvasive test for determining elevated levels of blood urea
      nitrogen (BUN) may be useful under circumstances in which there is limited access
      to laboratories. Because saliva urea nitrogen (SUN) parallels BUN, we
      investigated the diagnostic performance of a semiquantitative SUN dipstick to
      test for elevated BUN levels in patients with chronic kidney disease (CKD).
      MATERIALS AND METHODS: Patients with CKD Stages 1 to 5D were studied. 50 ul of
      saliva were transferred onto the SUN test strip (Integrated Biomedical
      Technology, Elkhart, Indiana, IN, USA). SUN was determined after 1 minute by
      visual comparison of the color of the moistened test pad with 6 calibrated color
      blocks. Interobserver reproducibility was evaluated by independent observers,
      masked to urea concentrations of 6 calibrated urea solutions. Correlation between
      SUN and BUN was quantified by Spearman's rank correlation coefficient (RS), Kappa
      Statistic was employed to evaluate within-sample reproducibility of duplicates.
      Receiver operating characteristic (ROC) analysis was used to assess the
      diagnostic performance of SUN. RESULTS: 68 patients (31 females, 60 +/- 14 years;
      34 hemodialysis patients, 34 patients CKD Stages 1 - 4) were studied.
      Interobserver coefficient of variation was 4.9% at SUN levels > 50 mg/dl; within
      sample reproducibility was 90%. SUN and BUN were correlated significantly (RS =
      0.63; p < 0.01). Elevated BUN was diagnosed with high accuracy by SUN
      determination (area under the ROC curve: 0.90 (95% CI 0.85 - 0.95)). CONCLUSION:
      Semiquantitative dipstick measurements of SUN can reliably identify CKD patients
      with elevated BUN levels.

PMID- 21722603
TI  - Viral hepatitis in renal transplantation.
AB  - Chronic viral hepatitis remains common in the hemodialysis (HD) and renal
      transplantation population although measures to limit spread of hepatitis
      infection in HD units have markedly reduced its prevalence. Our review focuses on
      the current management of hepatitis B and C infections in renal transplant
      candidates before and after renal transplantation.

PMID- 21722604
TI  - Epstein-Barr virus load for early detection of lymphoproliferative disorder in
      pediatric renal transplant recipients.
AB  - AIM: The aims of this study were to establish a protocol for monitoring Epstein
      Barr virus (EBV) infection for identification of pediatric renal transplant
      recipients with a high risk of developing posttransplant lymphoproliferative
      disorder (PTLD) and to predict the development of PTLD. SUBJECTS AND METHODS:
      Peripheral blood mononuclear cells (PBMCs) and plasma EBV loads were measured by
      nested PCR (n-PCR) and real-time PCR (r-PCR) every 1 - 3 months after grafting in
      17 pediatric recipients who were seronegative for EBV before grafting (4 with EBV
      associated symptoms, including 2 with PTLD (Group A); 6 with asymptomatic
      persistent high EBV loads in PBMCs of > 1,000 copies/ugDNA for over 6 months
      (Group B); and 7 with neither EBV-associated symptoms nor persistent high EBV
      loads in PBMCs (Group C)). RESULTS: n-PCR revealed EBV-DNA in PBMCs from all
      patients. The EBV genome was present in plasma in 3 (75%), 1 (17%), and 0 (0%) in
      Groups A, B and C (p < 0.01 for A vs. B and A vs. C). EBV loads detected by r-PCR
      in PBMCs were significantly higher in Groups A (p < 0.05) and B (p < 0.01)
      compared to Group C. EBV genomes in plasma were detected by n- and r-PCR in only
      the 2 cases with PTLD. One patient with lymphadenitis in Group A and 1 patient in
      Group B had EBV-DNA in plasma based on n-PCR, but the viral loads using r-PCR
      were < 250 copies/ml. CONCLUSION: EBV loads in PBMCs alone are insufficient for
      predicting EBV-associated symptoms including PTLD. Plasma EBV loads (over 250
      copies/ml) estimated by r-PCR may be useful to distinguish PTLD from other EBV
      associated diseases or asymptomatic viremia.

PMID- 21722605
TI  - Henoch-Schonlein purpura in adults is not uncommon in elderly patients with an
      adverse prognosis.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) is a fairly common disease in children
      and adolescents. There are only limited data available for adults. METHODS: A
      retrospective analysis was conducted to study renal manifestations in patients
      with HSP treated in our institution between 1982 and 2007. We divided our adult
      cohort according to age - under or over 60 years - to examine differences in
      elderly patients. RESULTS: HSP was identified in 2.2% of patients referred to us
      for kidney biopsy. Purpuric lesions and renal involvement were found in all
      patients. An important triggering factor for the development of HSP in our series
      was chronic alcohol intake. Forty percent of our patients fulfilled the WHO
      criteria for alcoholics. Renal involvement was particularly prominent in patients
      over 60 years of age. At disease onset, estimated glomerular filtration rate
      (eGFR) was 63% lower in the elderly. Within a median follow-up of 8 years, renal
      function was significantly better in younger adults than in the elderly. 32% of
      the elderly have shown Modification of Diet in Renal Disease (MDRD) < 20
      ml/min/1.73 m2 in contrast to only 7% in patients < 60 years. Furthermore,
      significantly more elderly patients reached end-stage renal failure. CONCLUSION:
      The data indicate that renal manifestation of HSP in the elderly is severe and
      its outcome relatively poor, and worsens when compared to patients < 60 years.

PMID- 21722606
TI  - Prednisone monotherapy induced remission in a group of patients with membranous
      lupus nephritis.
AB  - The treatment of membranous lupus nephritis (MLN) is still controversial in the
      literature. We conducted a retrospective analysis of patients in two medical
      centers of Sao Paulo-Brazil in order to evaluate the clinical response in
      patients submitted to either a regimen with prednisone alone or to a double
      immunosuppressive regimen (prednisone plus cyclophosphamide or prednisone plus
      azathioprine). METHODS: MLN female patients were enrolled in this retrospective
      study conducted from February 1999 to June 2007. Data were collected from the
      patients' medical charts. Race distribution was similar in both groups: Caucasian
      (72.3%) and Afro-Latin-American (27.7%). The prednisone regimen consisted of 1
      mg/kg/day for 8 weeks and tapering until 0.1 mg/kg/day (n = 29). The double
      immunosuppressive treatment consisted of the same doses of prednisone plus
      monthly intravenous cyclophosphamide or azathioprine for 6 months (n = 24).
      Criteria for remission (complete and partial) and renal function loss as well as
      flare criteria followed those used in the literature. RESULTS: There was no
      difference between the prednisone group and the double immunosuppressive group
      regarding age (33.2 +/- 9.4 vs. 29.1 +/- 9.1 y), estimated GFR (76.5 +/- 26.6 vs.
      74.1 +/- 39.6 ml/min/1.73 m2), serum albumin (2.8 +/- 0.7 vs. 2.6 +/- 0.3 g/dl),
      positive ANA (87.5 vs. 90.0%), positive anti- dsDNA (47.6 vs. 44.0%), renal
      SLEDAI indices (6.6 +/- 2.6 vs. 7.0 +/- 3.1), follow-up time (71 +/- 46 vs. 62 +/
      45 months), as well as proteinuria (3.1 +/- 1.9 vs. 4.8 +/- 2.4 g/day) and
      number of non-nephrotic patients (6 in the prednisone group vs. 3 in the double
      immunosuppressive group). The prednisone group presented higher C3 values (85.2
      +/- 31.5 vs. 62.3 +/- 41.6 U/ml, p = 0.04). Clinical and laboratory
      characteristics at 6 months and at last follow-up did not reveal any differences
      between treatment regimens. Renal survival after an 8-year follow-up did not
      differ in both groups (prednisone group 86.2% vs. double immunosuppressive group
      75%), and patients in both groups showed a high rate of renal flares (prednisone
      group 51.7% vs. double immunosuppressive group 62.5%). Univariate analysis showed
      that only patient age predicted flares (r = -0.048, p = 0.04). Borderline
      significance was obtained for proteinuria analysis (p = 0.07). Adverse effects
      did not differ between the groups. CONCLUSIONS: A regimen of corticosteroids in
      MLN induced a high remission rate after 6 months. Both treatment regimens showed
      a high flare rate and age was the only predictive parameter (r = -0.048, p =
      0.04). Renal survival after 8 years did not differ between the groups.

PMID- 21722607
TI  - Focal segmental glomerulosclerosis and partial deletion of chromosome 6p: a case
      report.
AB  - We treated a patient with 6p partial deletion syndrome diagnosed after
      proteinuria was detected during developmental examination 3 years after birth.
      External anomalies included ocular hypertelorism, saddle nose, elongated
      philtrum, tent-like lips, and low-set auricles. Mental retardation was evident.
      The karyotype was 46,XX,del(6) (p.22.1-p22.3) with an interstitial deletion. The
      kidneys showed no abnormality on imaging such as hydronephrosis, atrophy, or
      malformation. Examination of a renal biopsy specimen disclosed focal segmental
      glomerulosclerosis. No cardiac anomaly or Rieger anomaly, which often are present
      in this syndrome, were noted.

PMID- 21722608
TI  - Hemolytic uremic syndrome and rhabdomyolysis in a patient with succinate coenzyme
      Q reductase (complex II) deficiency.
AB  - Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic
      anemia, thrombocytopenia and acute renal failure. Besides diarrhea-associated
      HUS, due to verotoxin-producing Escherichia coli, in children HUS without
      prodromal diarrhea may be associated with other infectious and autoimmune
      diseases, genetic defects of the complement-regulator alternative-pathway, and
      inborn errors of vitamin B12 metabolism. Rhabdomyolysis is the dissolution of
      skeletal muscle due to various causes, including inborn errors of metabolism.
      Recurrent rhabdomyolysis and HUS have been previously described in one patient
      with a genetic defect of oxidative phosphorylation. We report the case of a 2
      year-old boy with recurrent HUS and rhabdomyolysis in whom a succinate coenzyme Q
      reductase (complex II) deficiency was diagnosed. We hypothesize that defects of
      oxidative phosphorylation could be another etiological factor in atypical HUS.

PMID- 21722609
TI  - Goodpasture's disease complicating human immunodeficiency virus infection.
AB  - Goodpasture's disease in association with human immunodeficiency virus (HIV) is
      rarely observed. Herein, we report a case of a 33-year-old Hispanic male who had
      both HIV and hepatitis C, and was subsequently diagnosed with autoantibodies to
      the glomerular basement membrane. On initial presentation he was anuric and
      hyperkalemic with an elevated creatinine. Hemodialysis was initiated, and a renal
      biopsy showed findings diagnostic of anti-glomerular basement membrane crescentic
      glomerulonephritis. Immunofluorescence microscopy showed strong (3+) linear
      staining of glomerular basement membranes by IgG, kappa; and lambda; light
      chains, and focal weaker staining of glomerular basement membranes for C3.
      Plasmapheresis, steroids and cyclophosphamide were all considered in treating
      this complex case. The patient received therapy with plasmapheresis and steroids
      during his initial hospitalization, but his renal function did not improve. He
      was discharged on hemodialysis 3 times per week. On a subsequent admission, the
      patient presented with symptoms and signs suggestive of pulmonary hemorrhage.
      Thus, plasmapheresis and cyclophosphamide were begun. His pulmonary symptoms
      improved with therapy, but he continued to require long-term hemodialysis. The
      development of Goodpasture's syndrome in a patient with HIV infection creates
      diagnostic and therapeutic dilemmas. The decision to treat the patient with
      immunosuppressive medications should lead to enhanced surveillance for
      infections.

PMID- 21722610
TI  - Two cases of nephrotic syndrome (NS)-induced acute kidney injury (AKI) associated
      with renal hypouricemia.
AB  - Renal hypouricemia is a clinical disorder attributed to an increased renal urate
      excretion rate and is well known to involve a high risk of urolithiasis and
      exercise-induced acute kidney injury (AKI). This report concerns two interesting
      cases of nephrotic syndrome (NS)-induced AKI associated with renal hypouricemia.
      A 64-year-old female (Case 1) and a 37-year-old male (Case 2) were hospitalized
      because of AKI (serum creatinine: 2.07 mg/dl and 3.3 mg/dl, respectively),
      oliguria and NS. They were treated with prednisolone and temporary hemodialysis.
      Renal function improved, but hypouricemia persisted during hospitalization.
      Histological findings in both cases led to a diagnosis of minimal change
      nephrotic syndrome and identification of the diuretic phase of tubulointerstitial
      damage because of findings such as acute tubular necrosis. Furthermore, distal
      tubules of Case 2 showed an amorphous mass, possibly a uric acid crystal.
      Analysis of the two cases with the URAT1 gene, encoded by SLC22A12, found a
      homozygous mutation in exon 4 (W258stop) of each one. Our cases show that
      patients with renal hypouricemia may be susceptible to AKI without involvement of
      exercise if they possess some facilitators. Renal hypouricemic patients should
      therefore be carefully examined for all complications from renal hypouricemia
      because of high risk of AKI.

PMID- 21722611
TI  - Seroprevalence to cytomegalovirus in the Portuguese population, 2002-2003.
AB  - The prevalence of cytomegalovirus (CMV) infections ranges between 50% and 85% in
      adults in the United States, and its epidemiology varies in different regions of
      the world and between socioeconomic and age groups. In Portugal, no study has
      been carried out to date to determine the prevalence of CMV in the general
      population. Under the second National Serological Survey conducted in continental
      Portugal in 2001-2002, we estimated the prevalence of individuals with antibodies
      to CMV using indirect immunofluorescence to detect virus-specific IgG. The
      population sample included 2,143 individuals of both sexes and different ages
      from all 18 districts in Portugal. The national seroprevalence of CMV was
      determined as 77%. We analysed the proportion of CMV IgG by sex, age group and
      district of residence. This was the first nationally representative study of
      seroprevalence of CMV in Portugal. The results of the study indicate that CMV
      infection is highly prevalent in the population and occurs mainly in the first
      years of life.

PMID- 21722612
TI  - Surveillance of West Nile virus disease, Tel Aviv district, Israel, 2005 to 2010.
AB  - We present the findings of a six-year surveillance period (2005-2010) of human
      West Nile virus (WNV) infection in Tel Aviv district, Israel. Initial
      notifications of positively identified patients received from the Central
      Virology Laboratory were followed by epidemiological investigations of the local
      district health office. During 2005-2010, 104 patients, 79 with WNV neuroinvasive
      and 25 with WNV non-neuroinvasive disease were reported. The median age of the
      patients with a neuroinvasive disease was 74 years (range: 15 to 95 years) and 53
      of such patients had encephalitis, 14 had acute flaccid paralysis, and 12 had
      meningitis. The case-fatality rate in these patients was 8%. The average annual
      incidence of neuroinvasive disease during 2005-2010 was 1.08 per 100,000
      population. The incidence declined by 86% steadily between 2005 and 2009 (p for
      trend=0.005), but increased by more than six-fold in 2010. Elderly (>=65 years)
      men, comprising 25 patients of whom 24 were chronically-ill, had the highest
      incidence of WNV encephalitis <0.001). These findings are concordant with
      previous data, at the national level, published in Israel and the United States.
      Notably, the percentage of previously healthy patients, who developed a
      neuroinvasive disease was the highest (37%, p=0.001) in the surveillance period
      in 2010.

PMID- 21722613
TI  - Household transmission of haemolytic uraemic syndrome associated with Escherichia
      coli O104:H4 in the Netherlands, May 2011.
AB  - Following the outbreak of haemolytic uraemic syndrome (HUS) and haemorrhagic
      colitis in Germany, two patients returning from a stay in Germany developed HUS
      due to Escherichia coli O104:H4 in the Netherlands. The index case developed
      symptoms eight days, and her child 15 days after their return. It is very likely
      that transmission resulted from secondary spread from mother to child.
      Recommendations should be made to prevent secondary transmission within
      households.

PMID- 21722614
TI  - Colonic ischaemia as a severe Shiga toxin/verotoxin producing Escherichia coli
      O104:H4 complication in a patient without haemolytic uraemic syndrome, Germany,
      June 2011.
AB  - An increasing rate of infections with Shiga toxin/verotoxin-producing Escherichia
      coli (STEC/VTEC) O104:H4 has been observed in Germany since May 2011, with
      unusually high numbers of patients suffering from haemolytic uraemic syndrome
      (HUS). We report a STEC/VTEC O104:H4 case without HUS, presenting with colonic
      ischaemia demanding surgery. This atypical clinical presentation of STEC O104:H4
      infection might indicate new severe complications associated with this uncommon
      strain, and highlights the importance of immediate interdisciplinary assessment
      of STEC/VTEC patients.

PMID- 21722615
TI  - The new face of enterohaemorrhagic Escherichia coli infections.

PMID- 21722616
TI  - Synthesis, characterization, cytotoxic activity and DNA binding properties of the
      novel dinuclear cobalt(III) complex with the condensation product of 2
      acetylpyridine and malonic acid dihydrazide.
AB  - A novel dinuclear cobalt(III) complex with the condensation product of 2
      acetylpyridine and malonic acid dihydrazide, N',N'(2)-bis[(1E)-1-(2
      pyridyl)ethylidene]propanedihydrazide was synthesized and characterized by
      elemental analysis, spectroscopy (NMR and infrared), and X-ray crystal analysis.
      The complex showed a moderate activity towards Artemia salina. The highest
      cytotoxic potential of the complex was observed on the epithelial breast cancer
      (MDA-361) cell line. The investigated complex induced apoptosis, the early
      apoptotic cells comprising 28.18%, compared to 5.64% of control cells in the same
      phase. The interaction of the complex with calf thymus DNA (CT-DNA) was monitored
      by blue shift and hyperchromism in the UV-vis spectra. The observed intrinsic
      binding constant (K(b)=4.2*10(5)M(-1)) together with structural analysis of the
      complex indicate the groove binding.

PMID- 21722617
TI  - Low-dose exposure to alkylphenols adversely affects the sexual development of
      Atlantic cod (Gadus morhua): acceleration of the onset of puberty and delayed
      seasonal gonad development in mature female cod.
AB  - Produced water (PW), a by-product of the oil-production process, contains large
      amount of alkylphenols (APs) and other harmful oil compounds. In the last 20
      years, there have been increasing concerns regarding the environmental impact of
      large increases in the amounts of PW released into the North Sea. We have
      previously shown that low levels of APs can induce disruption of the endocrine
      and reproductive systems of Atlantic cod (Gadus morhua). The aims of this follow
      up study were to: (i) identify the lowest observable effect concentration of APs;
      (ii) study the effects of exposure to real PW, obtained from a North Sea oil
      production platform; and (iii) study the biological mechanism of endocrine
      disruption in female cod. Fish were fed with feed paste containing several
      concentrations of four different APs (4-tert-butylphenol, 4-n-pentylphenol, 4-n
      hexylphenol and 4-n-heptylphenol) or real PW for 20 weeks throughout the normal
      period of vitellogenesis in Atlantic cod from October to January. Male and female
      cod, exposed to AP and PW, were compared to unexposed fish and to fish fed paste
      containing 17beta-oestradiol (E(2)). Approximately 60% of the females and 96% of
      the males in the unexposed groups were mature at the end of the experiment. Our
      results show that exposure to APs and E(2) have different effects depending on
      the developmental stage of the fish. We observed that juvenile females are
      advanced into puberty and maturation, while gonad development was delayed in both
      maturing females and males. The AP-exposed groups contained increased numbers of
      mature females, and significant differences between the untreated group and the
      AP-treated groups were seen down to a dose of 4 MUg AP/kg body weight. In the
      high-dose AP and the E(2) exposed groups, all females matured and no juveniles
      were seen. These results suggest that AP-exposure can affect the timing of the
      onset of puberty in fish even at extremely low concentrations. Importantly,
      similar effects were not seen in the fish that were exposed to real PW.

PMID- 21722618
TI  - Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on
      aggregation of the Alzheimer's Abeta peptide.
AB  - The effect of various types of nanoliposomes (associated with curcumin,
      phosphatidic acid, cardiolipin, or GM1 ganglioside) on the aggregation of the
      amyloid-beta(1-42) (Abeta(1-42)) peptide was investigated. Nanoliposomes
      incorporating curcumin (curcumin-liposomes) were prepared by adding curcumin in
      the lipid phase during liposome preparation, whereas curcumin surface-decorated
      liposomes were prepared by using a curcumin-lipid conjugate (lipid-S-curcumin
      liposomes) or by attaching a curcumin derivative on preformed liposomes by click
      chemistry (click-curcumin liposomes). The lipid ligands (phosphatidic acid,
      cardiolipin, or GM1) were also incorporated into nanoliposomes during their
      formation. All nanoliposomes with curcumin, or the curcumin derivative, were able
      to inhibit the formation of fibrillar and/or oligomeric Abeta in vitro. Of the
      three forms of curcumin liposomes tested, the click-curcumin type was by far the
      most effective. Liposomes with lipid ligands only inhibited Abeta fibril and
      oligomer formation at a very high ratio of liposome to peptide. Curcumin-based
      liposomes could be further developed as a novel treatment for Alzheimer's
      disease.

PMID- 21722619
TI  - The effect of high concentration and exposure duration of nanoceria on human lens
      epithelial cells.
AB  - Nanotechnology has the potential for treating diseases and conditions of ageing.
      The eye is particularly vulnerable, because chronic pathologies can lead to sight
      loss. Human lens epithelial cells were exposed to 10, 20, and 100 MUg/mL of
      negatively charged nanoceria for 48 and 72 hours; DNA damage and cell growth were
      assessed. Concentrations up to 100 MUg/mL for 48 hours did not cause measurable
      genotoxic effects. For exposures of 72 hours, concentrations above 10 MUg/mL
      showed small but statistically significant differences in DNA damage from
      negative controls. All treated samples were less damaged than positive controls.
      Cell growth, monitored for up to 7 days, did not show deviations in cell
      morphology or growth between treated and untreated samples. Whereas time of
      exposure may have greater effect than dosage, indicating potential for
      genotoxicity at higher exposures, human lens epithelial cells can sustain normal
      growth when exposed to concentrations of nanoceria of up to 100 MUg/mL. From the
      Clinical Editor: Human lens epithelial cells were exposed to various
      concentrations of negatively charged nanoceria for 48 and 72 hours to assess DNA
      damage and cell growth. The authors demonstrate that epithelial cells can sustain
      normal growth when exposed to concentrations of up to 100 MUg/mL, with time of
      exposure having a greater effect than dosage, indicating potential genotoxicity
      at higher exposures.

PMID- 21722620
TI  - Plasmodium berghei NK65 induces cerebral leukocyte recruitment in vivo: an
      intravital microscopic study.
AB  - Malaria is second only to tuberculosis as the leading cause of morbidity and
      mortality as a consequence of a single infectious agent. Much of the pathology of
      malaria arises from the inappropriate or excessive immune response mounted by the
      host in an attempt to eliminate the parasite. We here report the inflammatory
      changes observed in the cerebral microvasculature of C57BL/6 and BALB/c mice that
      had been inoculated with Plasmodium berghei NK65, a lethal strain of rodent
      malaria. Although no neurological signs were observed in experimentally infected
      mice, inflammation of the cerebral microvasculature was clearly evident.
      Histopathological analysis demonstrated that alterations in cerebral tissue were
      more intense in infected C57Bl/6 mice than in infected BALB/c animals. Intravital
      microscopic examination of the cerebral microvasculature revealed increased
      leukocyte rolling and adhesion in pial venules of infected mice compared with non
      infected animals. The extravasation of Evans blue dye into the cerebral
      parenchyma was also elevated in infected mice in comparison with their non
      infected counterparts. Additionally, protein levels of TNF-alpha, MIG/CXCL9, MCP
      1/CCL2, MIP-1alpha/CCL3 and RANTES/CCL5 were up-regulated in brain samples
      derived from infected C57Bl/6 mice. Taken together, the data reported here
      illustrate the complex strain-dependent relationships between leukocyte
      recruitment, blood brain barrier permeability and chemokine production.

PMID- 21722621
TI  - Standardization of epidermal growth factor receptor (EGFR) measurement by
      quantitative immunofluorescence and impact on antibody-based mutation detection
      in non-small cell lung cancer.
AB  - Challenges in measurement of epidermal growth factor receptor (EGFR) protein
      expression have led to conflicting data on its prognostic value and
      discontinuation of its use for prediction of response. Herein is described a
      quantitative standardized assay for EGFR and its use in a series of retrospective
      cohorts of patients with non-small cell lung cancer (NSCLC). The AQUA technology
      of quantitative immunofluorescence was used in conjunction with Western blot
      analysis to calculate the absolute concentration of EGFR in two independent NSCLC
      cohorts (170 from Yale New Haven Hospital and 335 from Sotiria and Patras
      Hospitals in Greece). EGFR and mutated EGFR were measured using D38B1 antibody
      and two mutation-specific antibodies. All patients positive or borderline for
      mutation-specific antibody were genotyped. A threshold for reproducible detection
      of EGFR was defined as 0.85 ng/MUg total protein. EGFR expression demonstrated no
      prognostic value in either cohort. The mutation rate was 1.79% in the Yale
      cohort, and 1.52% in the Sotiria/Patras cohort, with no antibody detection-based
      false-positive cases. No mutations were detected for EGFR concentrations <1.46
      ng/MUg total protein. In summary, accurate measurement of EGFR still shows no
      prognostic value in NSCLC. In these two population-based cohorts, the antibody
      based EGFR mutation rate was lower than has been frequently reported.

PMID- 21722622
TI  - Role of TGF-beta1 and TNF-alpha in IL-1beta mediated activation of proMMP-9 in
      pulmonary artery smooth muscle cells: involvement of an aprotinin sensitive
      protease.
AB  - We investigated the role of TGF-beta1 and TNF-alpha in mediating the effect of IL
      1beta in activating proMMP-9 and proMMP-2, and the involvement of an aprotinin
      sensitive protease in this scenario in bovine pulmonary artery smooth muscle
      cells. IL-1beta induces TGF-beta1 mediated stimulation of 92kDa proMMP-9 and
      72kDa proMMP-2 mRNA and protein expression; whereas, the elevated level of TNF
      alpha promotes activation of proMMP-9 and proMMP-2. Interestingly, TNF-alpha
      induced activation of proMMP-9 appeared to be mediated via a 43kDa aprotinin
      sensitive protease. TNF-alpha inhibited aprotinin and TIMP-1 mRNA and protein
      expression, which apparently facilitated the proteolytic conversion of proMMP-9
      to MMP-9 with the involvement of the aprotinin sensitive protease. The aprotinin
      sensitive protease did not activate proMMP-2 under IL-1beta stimulation, albeit a
      marked inhibition of TIMP-2 mRNA and protein expression were elicited by TNF
      alpha. Thus, IL-1beta induced stimulation of the two progelatinases occurs via
      different mechanisms.

PMID- 21722623
TI  - The role of pH on the thermodynamics and kinetics of muscle biochemistry: an in
      vivo study by (31)P-MRS in patients with myo-phosphorylase deficiency.
AB  - In this study we assessed DeltaG'(ATP) hydrolysis, cytosolic [ADP], and the rate
      of phosphocreatine recovery using Phosphorus Magnetic Resonance Spectroscopy in
      the calf muscle of a group of patients affected by glycogen myo-phosphorylase
      deficiency (McArdle disease). The goal was to ascertain whether and to what
      extent the deficit of the glycogenolytic pathway would affect the muscle energy
      balance. A typical feature of this pathology is the lack of intracellular
      acidosis. Therefore we posed the question of whether, in the absence of pH
      decrease, the rate of phosphocreatine recovery depends on the amount of
      phosphocreatine consumed during exercise. Results showed that at the end of
      exercise both [ADP] and DeltaG'(ATP) of patients were significantly higher than
      those of matched control groups reaching comparable levels of phosphocreatine
      concentration. Furthermore, in these patients we found that the rate of
      phosphocreatine recovery is not influenced by the amount of phosphocreatine
      consumed during exercise. These outcomes provide experimental evidence that: i)
      the intracellular acidification occurring in exercising skeletal muscle is a
      protective factor for the energy consumption; and ii) the influence of pH on the
      phosphocreatine recovery rate is at least in part related to the kinetic
      mechanisms of mitochondrial creatine kinase enzyme.

PMID- 21722625
TI  - The protective effect of magnesium lithospermate B against glucose-induced
      intracellular oxidative damage.
AB  - OBJECTIVES: To investigate the effects of magnesium lithospermate B (LAB) on
      intracellular reactive oxygen species (ROS) production induced by high dose of
      glucose or H(2)O(2), we explored the influences of LAB on the expression of heme
      oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells
      after treatment with high dose of glucose. MATERIALS AND METHODS: The total
      nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein
      Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and
      protein expression of HO-1 and Nrf2 were determined by quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: LAB
      reduced the ROS production in HEK293T cells cultured under oxidative stress. High
      dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time
      dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a
      dose-dependent manner treated with high dose of glucose. The amount of Nrf2
      translocation was enhanced after cells were pretreated with 50MUmol/L or
      100MUmol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1
      protein induced by high dose of glucose plus LAB. CONCLUSIONS: LAB plays an
      important role against glucose-induced intracellular oxidative damage. The
      enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via
      Nrf2 signal pathway.

PMID- 21722624
TI  - Effect of membrane tension on the electric field and dipole potential of lipid
      bilayer membrane.
AB  - The dipole potential of lipid bilayer membrane controls the difference in
      permeability of the membrane to oppositely charged ions. We have combined
      molecular dynamics (MD) simulations and experimental studies to determine changes
      in electric field and electrostatic potential of 1,2-dioleoyl-sn-glycero-3
      phosphocholine (DOPC) lipid bilayer in response to applied membrane tension. MD
      simulations based on CHARMM36 force field showed that electrostatic potential of
      DOPC bilayer decreases by ~45mV in the physiologically relevant range of membrane
      tension values (0 to 15dyn/cm). The electrostatic field exhibits a peak
      (~0.8*10(9)V/m) near the water/lipid interface which shifts by 0.9A towards the
      bilayer center at 15dyn/cm. Maximum membrane tension of 15dyn/cm caused 6.4%
      increase in area per lipid, 4.7% decrease in bilayer thickness and 1.4% increase
      in the volume of the bilayer. Dipole-potential sensitive fluorescent probes were
      used to detect membrane tension induced changes in DOPC vesicles exposed to
      osmotic stress. Experiments confirmed that dipole potential of DOPC bilayer
      decreases at higher membrane tensions. These results are suggestive of a
      potentially new mechanosensing mechanism by which mechanically induced structural
      changes in the lipid bilayer membrane could modulate the function of membrane
      proteins by altering electrostatic interactions and energetics of protein
      conformational states.

PMID- 21722626
TI  - Evolutionary importance of translation elongation factor eEF1A variant switching:
      eEF1A1 down-regulation in muscle is conserved in Xenopus but is controlled at a
      post-transcriptional level.
AB  - Translation elongation isoform eEF1A1 has a pivotal role in protein synthesis and
      is almost ubiquitously expressed. In mice and rats that transcription of the gene
      encoding eEF1A1 is downregulated to undetectable levels in muscle after weaning;
      eEF1A1 is then replaced by a separately encoded but closely related isoform
      eEF1A2, which has only previously been described in mammals. We now show that not
      only is eEF1A2 conserved in non-mammalian vertebrate species, but the down
      regulation of eEF1A1 protein in muscle is preserved in Xenopus, with the protein
      being undetectable by adulthood. Interestingly, though, this down-regulation is
      controlled post-transcriptionally, and levels of full-length eEF1A1 mRNA remain
      similar to those of eEF1A2. The switching off of eEF1A1 in muscle is therefore
      sufficiently important to have evolved through the use of repression operating at
      different levels in different species. The 3'UTR of eEF1A1 is highly conserved
      and contains predicted binding sites for several miRNAs, suggesting a possible
      method for controlling of expression. We suggest that isoform switching may have
      evolved because of a need for certain cell types to modify the well-established
      non-canonical functions of eEF1A1.

PMID- 21722627
TI  - An insight into the interaction mode between CheB and chemoreceptor from two
      crystal structures of CheB methylesterase catalytic domain.
AB  - We have determined 2.2 A resolution crystal structure of Thermotoga maritima CheB
      methylesterase domain to provide insight into the interaction mode between CheB
      and chemoreceptors. T. maritima CheB methylesterase domain has identical topology
      of a modified doubly-wound alpha/beta fold that was observed from the previously
      reported Salmonella typhimurium counterpart, but the analysis of the
      electrostatic potential surface near the catalytic triad indicated considerable
      charge distribution difference. As the CheB demethylation consensus sites of the
      chemoreceptors, the CheB substrate, are not uniquely conserved between T.
      maritima and S. typhimurium, such surfaces with differing electrostatic
      properties may reflect CheB regions that mediate protein-protein interaction. Via
      the computational docking of the two T. maritima and S. typhimurium CheB
      structures to the respective T. maritima and Escherichia coli chemoreceptors, we
      propose a CheB:chemoreceptor interaction mode.

PMID- 21722628
TI  - Discovery and biological characterization of 1-(1H-indol-3-yl)-9H-pyrido[3,4
      b]indole as an aryl hydrocarbon receptor activator generated by photoactivation
      of tryptophan by sunlight.
AB  - Activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) is required for AHR dependent transcriptional activation and TCDD
      toxicity. We previously reported that aqueous tryptophan exposed to sunlight
      through window glass (aTRP) contains multiple photoproducts, including the well
      characterized 6-formylindolo[3,2-b]carbazole (FICZ), capable of activating the
      AHR and inducing CYP1A and CYP1A-mediated enzyme activities. We report here the
      isolation from aTRP and chemical characterization and synthesis of 1-(1H-indol-3
      yl)-9H-pyrido[3,4-b]indole (IPI), a compound previously identified as a natural
      product of marine ascidia and now shown to be a TRP photoproduct with AHR
      inducing properties. IPI, FICZ and TCDD produced equieffective induction of CYP1A
      mediated 7-ethoxyresorufin deethylase (EROD) activity in chick embryo primary
      hepatocytes and mammalian Hepa1c1c7 cells. EROD induction by IPI was markedly
      curtailed in AHR-defective c35 cells, supporting the AHR dependence of the IPI
      response. Although IPI had a higher EC(50) for EROD induction than FICZ, the much
      larger amount of IPI than FICZ in aTRP makes IPI a prominent contributor to EROD
      induction in aTRP. IPI was detected in TRP-containing culture medium under
      ambient laboratory conditions but not in TRP-free medium, consistent with its
      production from TRP. Cotreatment of hepatocytes with submaximal EROD-inducing
      doses of IPI and FICZ or TCDD produced additive increases in EROD without
      synergistic or inhibitory interactions. IPI and FICZ were readily metabolized by
      cultured hepatocytes. In addition to increasing CYP1A4 mRNA and EROD, IPI and
      FICZ decreased hepatocyte phosphoenolpyruvate carboxykinase mRNA expression and
      glucose output, biological effects associated with TCDD metabolic dysregulation.
      The findings underscore a role for sunlight in generating AHR-activating
      bioactive molecules.

PMID- 21722629
TI  - Oxygen and cytokine-dependent changes in choline phospholipid saturation in
      hematopoietic progenitor cells detected by MALDI-TOF mass spectrometry.
AB  - The adaptation of cells to a changing environment is normally accompanied by
      rapid and/or chronic remodeling of membrane lipids. In order to understand the
      role played by membrane lipid metabolism in such responses, it is necessary to
      characterize in more detail the changes in membrane composition occurring in
      response to defined stimuli. There has been intense interest in characterizing
      the "stem cell niche" in recent years and an emerging consensus that stem cells
      are located in regions of low oxygen tension and probably well-isolated from the
      blood supply. We report here the use of matrix-assisted laser desorption and
      ionization time-of-flight mass spectrometry to monitor changes in the composition
      and saturation degree of choline phospholipids of hematopoietic progenitor
      (FDCPmix) cells under standard nutrient-rich culture conditions and at low oxygen
      and low glucose concentrations. We found that the increase in proliferation rate
      driven by high concentrations of interleukin-3 (IL-3) is associated with a
      decrease in membrane phosphatidylcholine (PC) 18:0/20:4 and sphingomyelin (SM)
      together with an increase in PC 18:0/18:2 and dihydro SM. Furthermore, this
      effect is most pronounced under low oxygen and low glucose conditions,
      independent of cell proliferation rates.

PMID- 21722630
TI  - Defective proventriculus specifies the ocellar region in the Drosophila head.
AB  - A pair of the Drosophila eye-antennal disc gives rise to four distinct organs
      (eyes, antennae, maxillary palps, and ocelli) and surrounding head cuticle.
      Developmental processes of this imaginal disc provide an excellent model system
      to study the mechanism of regional specification and subsequent organogenesis.
      The dorsal head capsule (vertex) of adult Drosophila is divided into three
      morphologically distinct subdomains: ocellar, frons, and orbital. The homeobox
      gene orthodenticle (otd) is required for head vertex development, and mutations
      that reduce or abolish otd expression in the vertex primordium lead to ocelliless
      flies. The homeodomain-containing transcriptional repressor Engrailed (En) is
      also involved in ocellar specification, and the En expression is completely lost
      in otd mutants. However, the molecular mechanism of ocellar specification remains
      elusive. Here, we provide evidence that the homeobox gene defective
      proventriculus (dve) is a downstream effector of Otd, and also that the repressor
      activity of Dve is required for en activation through a relief-of-repression
      mechanism. Furthermore, the Dve activity is involved in repression of the frons
      identity in an incoherent feedforward loop of Otd and Dve.

PMID- 21722631
TI  - Drosophila twin spot clones reveal cell division dynamics in regenerating
      imaginal discs.
AB  - Cell proliferation is required for tissue regeneration, yet the dynamics of
      proliferation during regeneration are not well understood. Here we investigated
      the proliferation of eye and leg regeneration in fragments of Drosophila imaginal
      discs. Using twin spot clones, we followed the proliferation and fates of sister
      cells arising from the same mother cell in the regeneration blastema. We show
      that the mother cell gives rise to two sisters that participate equally in
      regeneration. However, when cells switch disc identity and transdetermine to
      another fate, they fail to turn off the cell cycle and continue dividing long
      after regeneration is complete. We further demonstrate that the regeneration
      blastema moves as a sweep of proliferation, in which cells are displaced. Our
      results suggest that regenerating cells stop dividing once the missing parts are
      formed, but if they undergo a switch in cell fate, the proliferation clock is
      reset.

PMID- 21722632
TI  - Acetylsalicylic acid-induced oxidative stress, cell cycle arrest, apoptosis and
      mitochondrial dysfunction in human hepatoma HepG2 cells.
AB  - It is widely accepted that non-steroidal anti-inflammatory drugs (NSAIDs),
      including aspirin, reduce the risk of cancer. The anti-cancer and anti
      inflammatory effects of NSAIDs are associated with the inhibition of
      prostaglandin synthesis and cyclooxygenase-2 activity. Several other mechanisms
      which contribute to the anti-cancer effect of these drugs in different cancer
      models both in vivo and in vitro are also presumed to be involved. The precise
      molecular mechanism, however, is still not clear. We investigated, therefore, the
      effects of acetylsalicylic acid (ASA, aspirin) on multiple cellular and
      functional targets, including mitochondrial bioenergetics, using human hepatoma
      HepG2 cancer cells in culture. Our results demonstrate that ASA induced G0/G1
      cell cycle arrest and apoptosis in HepG2 cells. ASA increased the production of
      reactive oxygen species, reduced the cellular glutathione (GSH) pool and
      inhibited the activities of the mitochondrial respiratory enzyme complexes, NADH
      ubiquinone oxidoreductase (complex I), cytochrome c oxidase (complex IV) and the
      mitochondrial matrix enzyme, aconitase. Apoptosis was triggered by alteration in
      mitochondrial permeability transition, inhibition of ATP synthesis, decreased
      expression of the anti-apoptotic protein Bcl-2, release of cytochrome c and
      activation of pro-apoptotic caspase-3 and the DNA repairing enzyme, poly (-ADP
      ribose) polymerase (PARP). These findings strongly suggest that ASA-induced
      toxicity in human hepatoma HepG2 cells is mediated by increased metabolic and
      oxidative stress, accompanied by mitochondrial dysfunction which result in
      apoptosis.

PMID- 21722633
TI  - Mislocalization of large ARF-GEFs as a potential mechanism for BFA resistance in
      COG-deficient cells.
AB  - Defects in subunits of the conserved oligomeric Golgi (COG) complex represent a
      growing subset of congenital disorders of glycosylation (CDGs). In addition to
      altered protein glycosylation and vesicular trafficking, Cog-deficient patient
      fibroblasts exhibit a striking delay in the Golgi-disrupting effects of brefeldin
      A (BFA). Despite the diagnostic value of this BFA resistance, the molecular basis
      of this response is not known. To investigate potential mechanisms of resistance,
      we analyzed the localization of the large ARF-GEF, GBF1, in several Cog-deficient
      cell lines. Our results revealed mislocalization of GBF1 to non-Golgi
      compartments, in particular the ERGIC, within these cells. Biochemical analysis
      of GBF1 in control and BFA-treated fibroblasts demonstrated that the steady-state
      level and membrane recruitment is not substantially affected by COG deficiency,
      supporting a role for the COG complex in the localization but not membrane
      association of GBF1. We also showed that pretreatment of fibroblasts with
      bafilomycin resulted in a GBF1-independent BFA resistance that appears additive
      with the resistance associated with COG deficiency. These data provide new
      insight into the mechanism of BFA resistance in Cog-deficient cells by suggesting
      a role for impaired ARF-GEF localization.

PMID- 21722634
TI  - Transforming growth factor-beta2 utilizes the canonical Smad-signaling pathway to
      regulate tissue transglutaminase expression in human trabecular meshwork cells.
AB  - Transforming growth factor-beta2 (TGF-beta2) is elevated in the aqueous humor of
      patients with glaucoma. This growth factor is known to increase extracellular
      matrix (ECM) deposition in the trabecular meshwork (TM) as well as increase
      intraocular pressure (IOP) in perfused human cultured anterior eye segments. In
      addition overexpression of TGF-beta2 in the mouse TM leads to elevated IOP.
      Exogenous TGF-beta2 also increases tissue transglutaminase (TGM2) protein levels
      and enzyme activity in TM cells. TGM2 is a calcium-dependent enzyme that mediates
      cross-linking of ECM proteins, thus making ECM proteins resistant to enzymatic
      degradation and physical breakdown. We have investigated the signaling pathway by
      which TGF-beta2 induces TGM2 in human TM cells. Primary cultures of human TM
      cells (N = 6) were treated for 48 h with TGF-beta2 (0-10 ng/ml) in serum-free
      medium. TGM2 enzyme activity differences between non-treated and TGF-beta2
      treated TM cells were studied using a biotin cadaverine assay. Endogenous TGF
      beta2 protein levels were examined in normal trabecular meshwork (NTM) and
      glaucomatous trabecular meshwork (GTM) cell strains. Immunohistochemistry was
      used to evaluate the expression and co-localization of TGF-beta2 and TGM2 in NTM
      and GTM tissues. Activation of Smad3 signaling pathway was evaluated by western
      immunoblot analysis using phospho-specific antibodies following exogenous TGF
      beta2 treatment. Pharmacological specific inhibitor of Smad3 (SIS3) and short
      interfering (si)RNAs were used to suppress Smad3 activity and CTGF gene
      expression respectively. Endogenous TGF-beta2 levels were significantly elevated
      in cultured GTM cells (p < 0.05) when compared to NTM cells. Immunohistochemistry
      studies also demonstrated elevated expression and co-localization of both TGF
      beta2 and TGM2 in glaucoma human TM tissues. Exogenous TGF-beta2 increased both
      TGM2 protein levels and enzyme activity in TM cells. Phosphorylation of Smad3 was
      stimulated in TM cell strains by exogenous TGF-beta2. TGF-beta2 induction of TGM2
      was not inhibited with selective siRNA knockdown of CTGF. In contrast, a specific
      inhibitor of Smad3 (SIS3) and siRNA knockdown of Smad3 (p < 0.05) suppressed TGF
      beta2 induction of TGM2. This study demonstrated that TGF-beta2 induction of TGM2
      can be mediated via the canonical Smad-signaling pathway but does not appear to
      involve CTGF as a downstream mediator. Regulation of the Smad-signaling pathway
      in the TM may be useful in the therapy for glaucoma associated with aberrant TGF
      beta2 signaling.

PMID- 21722636
TI  - SUMOylation of Blimp-1 promotes its proteasomal degradation.
AB  - B lymphocyte induced maturation protein-1 (Blimp-1) is a transcription repressor
      of the Krueppel-like family. Blimp-1 plays important roles in developmental
      processes, such as of germ cells and hair follicle stem cells. In B lymphocytes
      Blimp-1 orchestrates the terminal differentiation into plasma cells. We
      discovered that Blimp-1 undergoes SUMOylation by SUMO-1. This SUMOylation is
      modulated by the SUMO protease SENP1. While Blimp-1 is relatively stable in 293T
      cells, a fusion with SUMO1 rendered it to rapid proteasomal degradation. Increase
      in SENP1 activity stabilized Blimp-1, while a decrease promoted its degradation.
      Our data indicate that SUMOylation of Blimp-1 regulates its intracellular
      stability.

PMID- 21722635
TI  - Phosphatidylinositol synthase is required for lens structural integrity and
      photoreceptor cell survival in the zebrafish eye.
AB  - The zebrafish lens opaque (lop) mutant was previously isolated in a genetic
      screen and shown to lack rod and cone photoreceptors and exhibit lens opacity, or
      cataract, at 7 days post-fertilization (dpf). In this manuscript, we provide four
      different lines of evidence demonstrating that the lop phenotype results from a
      defect in the cdipt (phosphatidylinositol (PI) synthase; CDP-diacylglycerol
      inositol 3-phosphatidyltransferase) gene. First, DNA sequence analysis revealed
      that the lop mutant contained a missense mutation in the lop open reading frame,
      which yields a nonconservative amino acid substitution (Ser-111-Cys) within the
      PI synthase catalytic domain. Second, morpholino-mediated knockdown of the cdipt
      encoded PI synthase protein phenocopied the cdipt(lop/lop) mutant, with abnormal
      lens epithelial and secondary fiber cell morphologies and reduced numbers of
      photoreceptors. Third, microinjection of in vitro transcribed, wild-type cdipt
      mRNA into 1-4 cell stage cdipt(lop/lop) embryos significantly reduced the
      percentage of larvae displaying lens opacity at 7 dpf. Fourth, a cdipt retroviral
      insertion allele, cdipt(hi559), exhibited similar lens and retinal abnormalities
      and failed to complement the cdipt(lop) mutant phenotype. To determine the
      initial cellular defects associated with the cdipt mutant, we examined homozygous
      cdipt(hi559/hi559) mutants prior to gross lens opacification at 6 dpf. The
      cdipt(hi559/hi559) mutants first exhibited photoreceptor layer disruption and
      photoreceptor cell death at 3 and 4 dpf, respectively, followed by lens
      dismorphogenesis by 5 dpf. RT-PCR revealed that the cdipt gene is maternally
      expressed and continues to be transcribed throughout development and into
      adulthood, in a wide variety of tissues. Using an anti-zebrafish PI synthase
      polyclonal antiserum, we localized the protein throughout the developing eye,
      including the photoreceptor layer and lens cortical secondary fiber cells. As
      expected, the polyclonal antiserum revealed that the PI synthase protein was
      reduced in amount in both the cdipt(lop/lop) and cdipt(hi559/hi559) mutants.
      Furthermore, we used a heterologous yeast phenotypic complementation assay to
      confirm that the wild-type zebrafish cdipt allele encodes functional PI synthase
      activity. Taken together, the cdipt-encoded PI synthase is required for survival
      of photoreceptor cells and lens epithelial and secondary cortical fiber cells.
      These zebrafish cdipt alleles represent excellent in vivo genetic tools to study
      the role of phosphatidylinositol and its phosphorylated derivatives in lens and
      photoreceptor development and maintenance.

PMID- 21722637
TI  - Evidence for direct binding of glycerol to photosystem I.
AB  - The interaction between glycerol and photosystem I (PSI) was investigated using
      low temperature single-molecule spectroscopy. PSI complexes were dissolved in
      three different solutions: in buffer solution, in 66% glycerol/buffer solution,
      and in 66% glycerol/buffer solution that was afterwards diluted by buffer; the
      final glycerol concentration was <10/00. Mean fluorescence spectra and
      intercomplex heterogeneity of PSI complexes in 66% glycerol/buffer solution and
      in the re-diluted solution show high similarity, but differ from complexes in
      buffer solution indicating that the glycerol concentration is not the determining
      factor modifying the spectral properties. However, the exposure of PSI to a high
      glycerol concentration during sample preparation affects PSI and the effect is
      maintained if glycerol is removed from the solution.

PMID- 21722638
TI  - Tubulin-blocked state of VDAC studied by polymer and ATP partitioning.
AB  - Recently reported functional interaction between voltage-dependent anion channel
      of the outer mitochondrial membrane, VDAC, and dimeric tubulin is observed as a
      reversible channel blockage. Using partitioning of poly-(ethylene glycol)s of
      different molecular weights and reversal potential measurements, we probe the
      size and ion selectivity of the fully open and tubulin-blocked states of VDAC
      reconstituted into planar lipid bilayers. While the effective radius of the
      channel decreases by only a factor of 1.34+/-0.15, the selectivity reverses from
      initially anionic to cationic. Directly measuring ATP partitioning we demonstrate
      that these changes prohibit ATP from entering the channel in its tubulin-blocked
      state.

PMID- 21722639
TI  - An unexpected link between angiotensinogen and thrombin.
AB  - Angiotensinogen is well known as source protein for a group of potent vasoactive
      hormones, however, a discrete biochemical activity of the angiotensinogen body is
      not known. Here we investigated angiotensinogen from the lamprey Lampetra
      fluviatilis (L. fluviatilis), an early-diverged vertebrate. The recombinantly
      produced protein showed progressive inhibitory activity towards human alpha
      thrombin with a second-order rate constant of 2.6*10(4) M(-1) min(-1). Heparin
      enhanced the reaction rate >800-fold with a bell-shaped dose-response curve and a
      stoichiometry of inhibition (SI) of 1.3, revealing lamprey angiotensinogen as an
      effective alpha-thrombin inhibitor. Genomic, biochemical, and protein sequence
      data indicate that angiotensinogen and heparin cofactor II (HCII) originated from
      a common ancestral thrombin antagonist, thus providing insight into an early
      stage of thrombin control.

PMID- 21722640
TI  - An unusual case of ulcerative duodenitis.

PMID- 21722641
TI  - Ecdysteroid receptor from the American lobster Homarus americanus: EcR/RXR
      isoform cloning and ligand-binding properties.
AB  - In arthropods, ecdysteroids regulate molting by activating a heterodimer formed
      by the ecdysone receptor (EcR) and retinoid X receptor (RXR). While this
      mechanism is similar in insects and crustaceans, variation in receptor splicing,
      dimerization and ligand affinity adds specificity to molting processes. This
      study reports the EcR and RXR sequences from American lobster, a commercially and
      ecologically important crustacean. We cloned two EcR splice variants, both of
      which specifically bind ponasterone A, and two RXR variants, both of which
      enhance binding of ponasterone A to the EcR. Lobster EcR has high affinity for
      ponasterone A and muristerone and moderately high affinity for the insecticide
      tebufenozide. Bisphenol A, diethyl phthalate, and two polychlorinated biphenyls
      (PCB 29 and PCB 30), environmental chemicals shown to interfere with crustacean
      molting, showed little or no affinity for lobster EcR. These studies establish
      the molecular basis for investigation of lobster ecdysteroid signaling and signal
      disruption by environmental chemicals.

PMID- 21722642
TI  - Variation in CAG repeat length of the androgen receptor gene predicts variables
      associated with intrasexual competitiveness in human males.
AB  - An expanding body of research suggests that circulating androgens regulate the
      allocation of energy between mating and survival effort in human males, with
      higher androgen levels promoting greater investment in mating effort. Because
      variations in the number of CAG codon repeats in the human androgen receptor (AR)
      gene appear to modulate the phenotypic effects of androgens - with shorter repeat
      lengths associated with greater androgenic effects per unit androgen -
      polymorphisms in this gene may predict trait-like individual differences in the
      degree to which men are calibrated toward greater mating effort. Consistent with
      this, men in the present study with shorter CAG repeat lengths exhibited greater
      upper body strength and scored higher on self-report measures of dominance and
      prestige, all of which are argued to be indices of mating effort. Repeat length
      failed to predict sociosexual orientation (i.e. pursuit of short-term mating
      relationships), however, suggesting that the traits correlated with this
      polymorphism may be primarily associated with intrasexual competitiveness in the
      service of long-term mating effort. None of these measures of mating effort was
      related to baseline testosterone concentrations (either as main effects or as
      interactions with CAG repeat length), implying that long-term androgen exposure
      associated with AR gene polymorphisms may account for more variance in some
      androgen-dependent traits than does current testosterone concentration. These
      findings provide further evidence for the importance of the CAG repeat
      polymorphism in the AR gene in explaining a broad range of individual differences
      in human males.

PMID- 21722643
TI  - Long-term alteration of anxiolytic effects of ovarian hormones in female mice by
      a peripubertal immune challenge.
AB  - Recent reports indicate that exposure to some stressors, such as shipping or
      immune challenge with the bacterial endotoxin, lipopolysaccharide (LPS), during
      the peripubertal period reduces sexual receptivity in response to ovarian
      hormones in adulthood. We hypothesized that a peripubertal immune challenge would
      also disrupt the response of a non-reproductive behavior, anxiety-like behavior,
      to ovarian hormones in adulthood. Female C57Bl/6 mice were injected with LPS
      during the peripubertal period and tested for anxiety-like behavior in adulthood,
      following ovariectomy and ovarian hormone treatment. Treatment with estradiol
      followed by progesterone reduced anxiety-like behavior in control, but not LPS
      treated females. We next determined if the disruptive effect of LPS on adult
      behavior were limited to the peripubertal period by treating mice with LPS either
      during this period or in adulthood. LPS treatment during the peripubertal period
      disrupted the anxiolytic effect of ovarian hormones, whereas treatment in
      adulthood did not. We further tested if this model of peripubertal immune
      challenge was applicable to an outbred strain of mice (CD-1). Similar to C57Bl/6
      mice, LPS treatment during the peripubertal period, but not later, disrupted the
      anxiolytic effect of estradiol and progesterone. These data suggest that a
      peripubertal immune challenge disrupts the regulation of anxiety-like behavior by
      ovarian hormones in a manner that persists at least for weeks after the
      termination of the immune challenge.

PMID- 21722644
TI  - Perceived stress, common health complaints and diurnal patterns of cortisol
      secretion in young, otherwise healthy individuals.
AB  - Research has frequently linked perceived stress with changes in subjective and
      objective measures of ill health; however, additional assessment should consider
      the physiological mechanisms mediating these effects. This study investigated
      whether differential patterns of cortisol secretion might partially mediate
      perceived stress related disparities in common health complaints in young,
      otherwise healthy individuals. To capture the kinds of health complaints commonly
      reported in this population, the Pennebaker Inventory of Limbic Languidness
      (PILL) was selected. To capture important parameters of the diurnal profile,
      cortisol was sampled at waking, 30 minutes post waking, 1200 h and 2200 h on
      three consecutive weekdays. Results revealed flatter diurnal cortisol slopes and
      elevated mean diurnal output (characterised by HPA hyperactivity in the evening)
      for participants in the higher stress group. Participants that reported higher
      perceived levels of stress also reported experiencing common health complaints
      with markedly greater frequency; however, these disparities were abolished when
      mean diurnal output of cortisol was statistically controlled. While dysregulation
      of basal HPA activity has been implicated in the aetiologies of chronic illness,
      findings reported here implicated hypersecretion of cortisol as one physiological
      pathway, partially mediating perceived stress related disparities in the kinds of
      common health complaints that typically affect young, otherwise healthy
      individuals.

PMID- 21722645
TI  - Interaction between sulphur mobilisation proteins SufB and SufC: evidence for an
      iron-sulphur cluster biogenesis pathway in the apicoplast of Plasmodium
      falciparum.
AB  - The plastid of Plasmodium falciparum, the apicoplast, performs metabolic
      functions essential to the parasite. Various reactions in the plastid require the
      assembly of [Fe-S] prosthetic groups on participating proteins as well as the
      reductant activity of ferredoxin that is converted from its apo-form by the
      assembly of [Fe-S] clusters inside the apicoplast. The [Fe-S] assembly pathway
      involving sulphur mobilising Suf proteins has been predicted to function in the
      apicoplast with one component (PfSufB) encoded by the plastid genome itself. We
      demonstrate the ATPase activity of recombinant P. falciparum nuclear-encoded SufC
      and its localisation in the apicoplast. Further, an internal region of apicoplast
      SufB was used to detect PfSufB-PfSufC interaction in vitro; co-elution of SufB
      from parasite lysate with recombinant PfSufC on an affinity column also indicated
      an interaction of the two proteins. As a departure from bacterial SufB and
      similar to reported plant plastid SufB, apicoplast SufB exhibited ATPase
      activity, suggesting the evolution of specialised functions in the plastid
      counterparts. Our results provide experimental evidence for an active Suf pathway
      in the Plasmodium apicoplast.

PMID- 21722646
TI  - Naegleria gruberi metabolism.
AB  - The completion of the genome project for Naegleria gruberi provides a unique
      insight into the metabolic capacities of an organism, for which there is an
      almost complete lack of experimental data. The metabolism of Naegleria seems to
      be extremely versatile, as can be expected for a free-living amoeboflagellate,
      but although considered to be fully aerobic, its genome also predicts important
      anaerobic traits. Other predictions are that carbohydrates are oxidised to carbon
      dioxide and water when oxygen is not limiting and that in the absence of oxygen
      the end-products will be succinate, acetate and minor quantities of ethanol and D
      lactate. The hybrid mitochondrion/hydrogenosome has both cytochromes and an [Fe]
      hydrogenase, but seems to lack pyruvate-ferredoxin oxidoreductase. Genomic
      information also provides the possibility to identify drugs with a possible mode
      of action in the fatal primary amoebic meningoencephalitis caused by the closely
      related opportunistic pathogen Naegleria fowleri.

PMID- 21722647
TI  - Enhancement of immunohistochemical staining of scrapie proteins and immune cells
      within lymph nodes of early scrapie-infected sheep.
AB  - Transmissible spongiform encephalopathies (TSE) are a group of fatal
      neurodegenerative diseases that affect animals as well as humans. The oldest of
      these diseases is Scrapie seen in sheep. Scrapie is caused by an altered form
      (PrP(sc)), capable of inducing "self-replication" of the normal host prion
      protein (PrP(c)). There is currently no universal standard for antigen retrieval
      when using immunohistochemistry to simultaneously stain the PrP(c) protein and
      other cellular markers. The use of formalin-fixed tissue creates a challenge by
      concealing the antigenic sites where an antibody would bind, and lengthy antigen
      retrieval methods must be applied in order to facilitate staining. Further
      complicating sheep tissue immunohistochemistry is a significant lack of
      commercial antibodies to sheep cell markers available in research. Here we
      developed a novel immunohistochemical technique using trypsin, formic acid, and
      hydrated autoclaving using citraconic anhydride buffer to increase sensitivity of
      staining for scrapie proteins and immune cell subsets. This allowed us to stain
      and identify cells within lymphoid tissue associated with early lymphoid
      pathogenesis in scrapie.

PMID- 21722648
TI  - Moulting of insect tracheae captured by light and electron-microscopy in the
      metathoracic femur of a third instar locust Locusta migratoria.
AB  - The insect tracheal system is an air-filled branching network of internal tubing
      that functions to exchange respiratory gases between the tissues and the
      environment. The light and electron-micrographs presented in this study show
      tracheae in the process of moulting, captured from the metathoracic hopping femur
      of a juvenile third instar locust (Locusta migratoria). The images provide
      evidence for the detachment of the cuticular intima from the tracheal epithelial
      cells, the presence of moulting fluid between the new and old cuticle layers, and
      the withdrawal of the shed cuticular lining through larger upstream regions of
      the tracheal system during moulting. The micrographs also reveal that the
      cuticular intima of the fine terminal branches of the tracheal system is cast at
      ecdysis. Therefore, the hypothesis that tracheoles retain their cuticle lining at
      each moult may not apply to all insect species or developmental stages.

PMID- 21722649
TI  - Mutational analysis and modeling reveal functionally critical residues in
      transmembrane segments 1 and 3 of the UapA transporter.
AB  - Earlier, we identified mutations in the first transmembrane segment (TMS1) of
      UapA, a uric acid-xanthine transporter in Aspergillus nidulans, that affect its
      turnover and subcellular localization. Here, we use one of these mutations (H86D)
      and a novel mutation (I74D) as well as genetic suppressors of them, to show that
      TMS1 is a key domain for proper folding, trafficking and turnover. Kinetic
      analysis of mutants further revealed that partial misfolding and deficient
      trafficking of UapA does not affect its affinity for xanthine transport, but
      reduces that of uric acid and confers a degree of promiscuity towards the binding
      of other purines. This result strengthens the idea that subtle interactions among
      domains not directly involved in substrate binding refine the selectivity of
      UapA. Characterization of second-site suppressors of H86D revealed a genetic
      interaction of TMS1 with TMS3, the latter segment shown for the first time to be
      important for UapA function. Systematic mutational analysis of polar and
      conserved residues in TMS3 showed that Ser154 is crucial for UapA transport
      activity. Our results are in agreement with a topological model of UapA built on
      the recently published structure of UraA, a bacterial homolog of UapA.

PMID- 21722650
TI  - The structure of LL-diaminopimelate aminotransferase from Chlamydia trachomatis:
      implications for its broad substrate specificity.
AB  - We have previously reported the structures of the native holo and substrate-bound
      forms of LL-diaminopimelate aminotransferase from Arabidopsis thaliana (AtDAP
      AT). Here, we report the crystal and molecular structures of the LL
      diaminopimelate aminotransferase from Chlamydia trachomatis (CtDAP-AT) in the apo
      form and the pyridoxal-5'-phosphate-bound form. The molecular structure of CtDAP
      AT shows that its overall fold is essentially identical with that of AtDAP-AT
      except that CtDAP-AT adopts an "open" conformation as opposed to the "closed"
      conformation of AtDAP-AT. Although AtDAP-AT and CtDAP-AT are approximately 40%
      identical in their primary sequence, they have major differences in their
      substrate specificities; AtDAP-AT is highly specific for LL-DAP, whereas CtDAP-AT
      accepts a wider range of substrates. Since all of the residues involved in
      substrate recognition are highly conserved between AtDAP-AT and CtDAP-AT, we
      propose that differences in flexibility of the loops lining the active-site
      region between the two enzymes likely account for the differences in substrate
      specificity.

PMID- 21722651
TI  - Reactive oxygen species mediate adipocyte differentiation in mesenchymal stem
      cells.
AB  - AIMS: Mesenchymal stem cells (MSC) have the potential to differentiate into
      various cell lineages, including adipocytes and osteoblasts. The formation of
      adipose tissue involves the commitment of MSC to the preadipocyte lineage and the
      differentiation of preadipocytes into mature adipocytes. In the present study, we
      investigated the involvement of reactive oxygen species (ROS) in adipocyte
      differentiation from MSC. MAIN METHODS: ROS signaling was evaluated by the
      effects of antioxidant N-acetyl-l-cysteine (NAC) or shRNA against NAD(P)H oxidase
      in the multipotent mesenchymal stem cell line 10T1/2 cells. Intracellular ROS was
      measured using an H(2)DCF dye. KEY FINDINGS: We found that NAC blocked adipocyte
      differentiation in MSC. An H(2)DCF assay revealed that differentiation-inducing
      agents induced ROS generation. These data suggest that ROS is involved in
      adipocyte differentiation in MSC. Next, we examined the source of ROS. Knockdown
      of NAD(P)H oxidase 4 (Nox4) by RNA interference inhibited ROS production and
      adipocyte differentiation by differentiation-inducing agents. Furthermore,
      treatment with NAC blocked the transcriptional activation of CREB, and the
      expression of dominant-negative mutants of CREB inhibited adipocyte
      differentiation. SIGNIFICANCE: The findings suggest that the increase in the
      intracellular ROS level via Nox4 mediates adipocyte differentiation through CREB
      in MSC. This data will provide new insight into the drug development for obesity.

PMID- 21722652
TI  - The biological effect of pharmacological treatment on dimethylaminohydrolases
      (DDAH-1) and cationic amino acid transporter-1 (CAT-1) expression in patients
      with acute congestive heart failure.
AB  - AIM: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric
      oxide (NO) which plays an important role in controlling vascular tone and
      regulates the contractile properties of cardiac myocytes. The aim of this study
      was to investigate the effect of pharmacological treatment on symmetric
      dimethylarginine (SDMA), ADMA and arginine plasma concentrations in patients with
      acute congestive heart failure (ACHF) through the evaluation of type-1 system
      cationic amino acid transporter-1/type 1 dimethylarginine dimethylaminohydrolases
      1 (CAT-1/DDAH-1). METHODS AND RESULTS: 25 hospitalized cardiology patients with
      symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular
      (LV) function (ejection fraction<35%) were included in the study. ADMA, SDMA, and
      arginine plasma concentrations were assessed before and after pharmacological
      treatment by high performance liquid chromatography. All patients received an
      adequate pharmacological treatment for ACHF. ADMA and SDMA plasma levels were
      significantly higher after pharmacological treatment respect to baseline values
      (pre-treatment) (0.75 vs 0.48; 1.31 vs 1.03; p<0.01). Arginine plasma
      concentration was significantly lower after therapy respect to baseline values
      (0.78 vs 0.99; p<0.01). This is associated more with the modulation of DDAH-1
      protein than with of CAT-1 system transport. CONCLUSIONS: In patients with ACHF,
      acute renal impairment function and the modulation of metabolism and
      extracellular transport by the DDAH-1/CAT-1 system determine high ADMA and SDMA
      levels after therapy for acute congestive heart failure.

PMID- 21722653
TI  - Impaired microvascular flow motion in subclinical diabetic feet with sudomotor
      dysfunction.
AB  - Impaired cutaneous blood flow and sweating dysfunction might be among the
      earliest manifestations of diabetic autonomic neuropathy. This study assessed the
      pathophysiological basis underlying skin vasomotion changes and their relation
      with progressive sudomotor dysfunction and other autonomic and somatic measures
      in subclinical diabetic feet. Laser Doppler skin perfusion was assessed on 68
      diabetic and 25 control subjects. The low-frequency vasomotion was transformed
      into three frequency intervals 0.0095-0.021, 0.021-0.052 and 0.052-0.145 Hz,
      respectively, for the investigation of endothelial, neurogenic and myogenic
      effects on microcirculatory alterations. The diabetic patients were categorized
      into three groups by increasing severity of sudomotor dysfunction: SSR+
      (sympathetic skin response present; 27 patients), SSR- (SSR absent; 23 patients)
      and at-risk (SSR absent and of preulcerative cracked skin; 18 patients). All
      diabetic patients underwent nerve conduction and cardiovascular autonomic
      studies. The total spectral and endothelial activity was significantly decreased
      only in the at-risk group. The SSR- group had lower neurogenic vasomotion than
      the SSR+ group (p<0.05). Although no statistical difference was noted between any
      group in absolute myogenic spectrum, the SSR- group had higher normalized
      myogenic activity than the SSR+ group (p<0.01). The larger drop in orthostatic
      pressure was paralleled by a reduction in the myogenic amplitude (r=-0.33,
      p<0.01). These results suggested that early impairment of low-frequency flow
      motion correlated closely with the presence of sudomotor dysfunction of
      subclinical feet mainly in neurogenic and endothelial components. Impaired
      systemic vascular tone as manifested by orthostatic hypotension was proportional
      to the degree of myogenic dysregulation in diabetic patients.

PMID- 21722654
TI  - Pharmacological reversal of cognitive bias in the chick anxiety-depression model.
AB  - Cognitive bias presents in clinical populations where anxious individuals adopt a
      more pessimistic interpretation of ambiguous aversive stimuli and depressed
      individuals adopt both a more pessimistic interpretation of ambiguous aversive
      stimuli and a less optimistic interpretation of ambiguous appetitive stimuli.
      These biases have been reversed by anxiolytics and antidepressants. In the
      current study, chicks exposed to an isolation stressor of 5-min to induce an
      anxiety-like state or 60-min to induce a depressive-like state were tested in a
      straight alley maze to a series of morphed ambiguous appetitive (chick
      silhouette) to aversive (owl silhouette) cues. Chicks in the depression-like
      state displayed more pessimistic-like and less optimistic-like approach behavior
      to ambiguous aversive and appetitive cues, respectively. Both forms of cognitive
      bias were reversed by 15.0 mg/kg imipramine. Chicks in anxiety-like state
      displayed more pessimistic-like approach behavior under the ambiguous aversive
      stimulus cues. However, 0.10 mg/kg clonidine produced modest sedation and thus,
      was ineffective at reversing this bias. The observation that cognitive biases of
      more pessimism and less optimism can be reversed in the depression-like phase by
      imipramine adds to the validity of the chick anxiety-depression model as a
      neuropsychiatric simulation. This article is part of a Special Issue entitled
      'Anxiety and Depression'.

PMID- 21722655
TI  - Predictive gaze shifts elicited during observed and performed actions in 10-month
      old infants and adults.
AB  - We asked whether people's actions are understood by projecting them onto one's
      own action programs, according to the direct matching hypothesis, and whether
      this mode of control functions in infants. Adults' and infants' gaze and hand
      movements were measured in two live situations. The task was either to move an
      object between two places in the visual field, or to observe the corresponding
      action performed by another person. When performing the action, infants and
      adults behaved strikingly similar. Hand and gaze movements were simultaneously
      initiated and gaze arrived at the goal ahead of the hand. When observing the
      actions, the initiation of the gaze shift was delayed relative to the observed
      hand movement in both infants and adults, but it still arrived at the goal ahead
      of the hand. For both the performance and observation of actions the
      proactiveness of gaze shifts was associated with saccades ahead of the velocity
      peak of the hand. The close similarity between adults' and infants' actions when
      performing the movements and the great advantage of the adults when observing
      them support the conclusion that one's own motor actions develop ahead of the
      ability to predict other people's actions.

PMID- 21722656
TI  - Magical ideation, creativity, handedness, and cerebral asymmetries: a combined
      behavioural and fMRI study.
AB  - Magical ideation has been shown to be related to measures of hand preference, in
      which those with mixed handedness exhibit higher levels of magical ideation than
      those with either consistent left- or right-handedness. It is unclear whether the
      relation between magical ideation and hand preference is the result of a bias in
      questionnaire-taking behaviour or of some neuropsychological concomitant of
      cerebral specialization. We sought to replicate this finding and further
      investigate how magical ideation is related to other measures of laterality,
      including handedness based on finger-tapping performance, and cerebral
      asymmetries for language, spatial judgment, and face processing as revealed by
      fMRI. Creative achievement was also assessed by questionnaire and correlated with
      magical ideation and the other measures. Magical ideation and creativity were
      positively correlated, and both were negatively correlated with absolute hand
      preference but not with hand performance or with any of the cerebral asymmetries
      being assessed. The results do not support the notion that the observed
      association between magical ideation, creativity and hand preference has a
      neuropsychological explanation based on reduced cerebral lateralization.

PMID- 21722657
TI  - Aerobic exercise improves hippocampal function and increases BDNF in the serum of
      young adult males.
AB  - Physical activity has been reported to improve cognitive function in humans and
      rodents, possibly via a brain-derived neurotrophic factor (BDNF)-regulated
      mechanism. In this study of human subjects, we have assessed the effects of acute
      and chronic exercise on performance of a face-name matching task, which recruits
      the hippocampus and associated structures of the medial temporal lobe, and the
      Stroop word-colour task, which does not, and have assessed circulating
      concentrations of BDNF and IGF-1 in parallel. The results show that a short
      period of high-intensity cycling results in enhancements in performance of the
      face-name matching, but not the Stroop, task. These changes in cognitive function
      were paralleled by increased concentration of BDNF, but not IGF-1, in the serum
      of exercising subjects. 3 weeks of cycling training had no effect on
      cardiovascular fitness, as assessed by VO2 scores, cognitive function, or serum
      BDNF concentration. Increases in fitness, cognitive function and serum BDNF
      response to acute exercise were observed following 5 weeks of aerobic training.
      These data indicate that both acute and chronic exercise improve medial temporal
      lobe function concomitant with increased concentrations of BDNF in the serum,
      suggesting a possible functional role for this neurotrophic factor in exercise
      induced cognitive enhancement in humans.

PMID- 21722658
TI  - Estradiol suppresses recovery of REM sleep following sleep deprivation in
      ovariectomized female rats.
AB  - Sleep complaints such as insufficient sleep and insomnia are twice as prevalent
      in women. Symptoms of sleep disruption are often coincident with changes in the
      gonadal hormone profile across a women's lifespan. Data from a number of
      different species, including humans, non-human primates and rodents strongly
      implicate a role for gonadal hormones in the modulation of sleep. In female rats,
      increased levels of circulating estradiol increase wakefulness and reduce sleep
      in the dark phase. In this study, we asked whether this reduction in sleep is
      driven by estradiol-dependent reduction in sleep need during the dark phase by
      assessing sleep before and after sleep deprivation (SD). Ovariectomized rats
      implanted with EEG telemetry transmitters were given Silastic capsules containing
      either 17-beta estradiol in sesame oil (E2) or sesame oil alone. After a 24-hour
      baseline, animals were sleep-deprived via gentle handling for the entire 12-hour
      light phase, and then allowed to recover. E2 treatment suppressed baseline REM
      sleep duration in the dark phase, but not NREM or Wake duration, within three
      days. While SD induced a compensatory increase in REM duration in both groups,
      this increase was smaller in E2-treated rats compared to oils, as measured in
      absolute duration as well as by relative increase over baseline. Thus, E2
      suppressed REM sleep in the dark phase both before and after SD. E2 also
      suppressed NREM and increased waking in the early- to mid-dark phase on the day
      after SD. NREM delta power tracked NREM sleep before and after SD, with small
      hormone-dependent reductions in delta power in recovery, but not spontaneous
      sleep. These results demonstrate that E2 powerfully and specifically suppresses
      spontaneous and recovery REM sleep in the dark phase, and suggest that ovarian
      steroids may consolidate circadian sleep-wake rhythms.

PMID- 21722659
TI  - Insights into ectopic estrogen receptor expression, nucleocytoplasmic
      distribution and interaction with chromatin obtained with new antibodies to
      estrogen receptors alpha and beta.
AB  - Recent reports have indicated that in cells ectopically expressing only ERalpha
      or the full-length hormone-binding isoform of ERbeta (ERbeta1), the receptors
      interact with chromatin with different efficacies and that antibodies capable of
      probing such interactions by chromatin immunoprecipitation (ChIP) are scarce. We
      therefore produced nine subtype and isoform-specific antibodies to ERalpha or
      ERbeta and validated their performance in receptor probing in cell lines and
      tissue biopsies by various immunochemical methods, including ChIP. We also
      produced clones of HEK-293 cells stably transfected with an estrogen response
      element (ERE)-dependent luciferase reporter and ERalpha or ERbeta1, in order to
      comparatively study their interaction with reporter ERE. We show that ERalpha was
      located in the nucleus and ERbeta1 in the cytoplasm as well as the nucleus of the
      stably transfected cells, while both receptors were found predominantly in the
      nucleus in transiently transfected cells and in all estrogen target tissues
      examined using the same antibodies. The cells displayed wild-type transcriptional
      activity and canonical regulation of ERE-dependent luciferase expression by
      estrogen agonists and antagonists. However, unlike ERalpha, ERbeta1 recruitment
      to the reporter ERE could be probed only by sequential ChIP with antibodies to
      receptor N- and C-terminus. These data suggest that in HEK-293 cells stably
      expressing ERalpha or ERbeta1, ER subtype-specific constraints apply to ERbeta1
      nuclear entry; and that in cells displaying cytoplasmic as well as nuclear
      localization of ERbeta1, sequential ChIP with different antibodies to the
      receptor is the method of choice for probing its interaction with chromatin.

PMID- 21722660
TI  - Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice.
AB  - Traffic related particulate matter air pollution is a risk factor for
      cardiovascular events; however, the biological mechanisms are unclear. We
      hypothesize that diesel exhaust (DE) inhalation induces up-regulation of
      inducible nitric oxide synthase (iNOS), which is known to contribute to vascular
      dysfunction, progression of atherosclerosis and ultimately cardiovascular
      morbidity and mortality. METHODS: ApoE knockout mice (30-week) were exposed to DE
      (at 200 MUg/m3 of particulate matter) or filtered-air (control) for 7 weeks (6
      h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated
      by immunohistochemistry and western blotting analysis. To examine iNOS activity,
      thoracic aortae were mounted in a wire myograph, and vasoconstriction stimulated
      by phenylephrine (PE) was measured with and without the presence of the specific
      inhibitor for iNOS (1400 W). NF-kappaB (p65) activity was examined by ELISA. The
      mRNA expression of iNOS and NF-kappaB (p65) was determined by real-time PCR.
      RESULTS: DE exposure significantly enhanced iNOS expression in the thoracic aorta
      (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated
      vasoconstriction by ~20%, which was partly reversed by 1400 W. The mRNA
      expression of iNOS and NF-kappaB was significantly augmented after DE exposure.
      NF-kappaB activity was enhanced 2-fold after DE inhalation, and the augmented NF
      kappaB activity was positively correlated with iNOS expression (R2=0.5998).
      CONCLUSIONS: We show that exposure to DE increases iNOS expression and activity
      possibly via NF-kappaB-mediated pathway. We suspect that DE exposure-caused up
      regulation of iNOS contributes to vascular dysfunction and atherogenesis, which
      could ultimately lead to urban air pollution-associated cardiovascular morbidity
      and mortality.

PMID- 21722661
TI  - Resolution of static and dynamic stimuli in the peripheral visual field.
AB  - In a clinical setting, emphasis is given to foveal visual function, and tests
      generally only utilize static stimuli. In this study, we measured static (SVA)
      and dynamic visual acuity (DVA) in the central and peripheral visual field on
      healthy, young emmetropic subjects using stationary and drifting Gabor patches.
      There were no differences between SVA and DVA in the peripheral visual field;
      however, SVA was superior to DVA in the fovea for both velocities tested. In
      addition, there was a clear naso-temporal asymmetry for both SVA and DVA for
      isoeccentric locations in the visual field beyond 10 degrees  eccentricity. The
      lack of difference in visual acuity between static and dynamic stimuli found in
      this study may reflect the use of drift-motion as opposed to displacement motion
      used in previous studies.

PMID- 21722662
TI  - Imaging retinal nerve fiber bundles using optical coherence tomography with
      adaptive optics.
AB  - Early detection of axonal tissue loss in retinal nerve fiber layer (RNFL) is
      critical for effective treatment and management of diseases such as glaucoma.
      This study aims to evaluate the capability of ultrahigh-resolution optical
      coherence tomography with adaptive optics (UHR-AO-OCT) for imaging the RNFL
      axonal bundles (RNFBs) with 3*3*3MUm(3) resolution in the eye. We used a research
      grade UHR-AO-OCT system to acquire 3 degrees *3 degrees  volumes in four normal
      subjects and one subject with an arcuate retinal nerve fiber layer defect (n=5;
      29-62years). Cross section (B-scans) and en face (C-scan) slices extracted from
      the volumes were used to assess visibility and size distribution of individual
      RNFBs. In one subject, we reimaged the same RNFBs twice over a 7month interval
      and compared bundle width and thickness between the two imaging sessions. Lastly
      we compared images of an arcuate RNFL defect acquired with UHR-AO-OCT and
      commercial OCT (Heidelberg Spectralis). Individual RNFBs were distinguishable in
      all subjects at 3 degrees  retinal eccentricity in both cross-sectional and en
      face views (width: 30-50MUm, thickness: 10-15MUm). At 6 degrees  retinal
      eccentricity, RNFBs were distinguishable in three of the five subjects in both
      views (width: 30-45MUm, thickness: 20-40MUm). Width and thickness RNFB
      measurements taken 7months apart were strongly correlated (p<0.0005). Mean
      difference and standard deviation of the differences between the two measurement
      sessions were -0.1+/-4.0MUm (width) and 0.3+/-1.5MUm (thickness). UHR-AO-OCT
      outperformed commercial OCT in terms of clarity of the microscopic retina. To our
      knowledge, these are the first measurements of RNFB cross section reported in the
      living human eye.

PMID- 21722663
TI  - Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward
      associated memory in rats.
AB  - Exposure to cues previously associated with drug intake leads to relapse by
      activating previously acquired memories. Based on previous findings, in which
      cannabinoid CB(1) receptors were found to be critically involved in specific
      aspects of learning and memory, we investigated the role of CB(1) receptors in
      nicotine reward memory using a rat conditioned place preference (CPP) model. In
      Experiment 1, rats were trained for CPP with alternating injections of nicotine
      (0.5mg/kg, s.c.) and saline to acquire the nicotine-conditioned memory. To
      examine the effects of rimonabant on the reconsolidation of nicotine reward
      memory, rats were administered rimonabant (0, 0.3, and 3.0mg/kg, i.p.)
      immediately after reexposure to the drug-paired context. In Experiment 2, rats
      were trained for CPP similarly to Experiment 1. To examine the effects of
      rimonabant on the reinstatement of nicotine reward memory, rimonabant (0, 0.3,
      and 3.0mg/kg, i.p.) was administered before the test of nicotine-induced CPP
      reinstatement. In Experiment 3, to evaluate whether rimonabant itself produces a
      reward memory, rats were trained for CPP with alternating injections of different
      doses of rimonabant (0, 0.3, and 3.0mg/kg) and saline. Rimonabant at a dose of
      3.0mg/kg significantly disrupted the reconsolidation of nicotine memory and
      significantly blocked the reinstatement of nicotine-induced CPP. However,
      rimonabant itself did not produce CPP. These findings provide clear evidence that
      CB(1) receptors play a role in nicotine reward memory, suggesting that CB(1)
      receptor antagonists may be a potential target for managing nicotine addiction.

PMID- 21722664
TI  - The impact of advances in treatment on the efficacy of mammography screening.
AB  - OBJECTIVE: The objective of this commentary is to argue that advances in therapy
      are diminishing the efficacy of mammography screening. METHOD: Key studies which
      demonstrate this effect are briefly reviewed. RESULTS: The author argues that,
      for screening to be beneficial, the treatment of screen-detected cancers must be
      more effective than that of clinically-detected cancers. If there was no
      effective therapy for breast cancer, then screening would offer no benefit.
      Furthermore, as breast cancer treatments improve over time, both the absolute and
      relative benefits of screening will diminish. This is evident in the overview of
      the nine successive mammography screening trials, which have shown a decrease in
      the benefit of mammography screening over time, with the three most recent trials
      showing no benefit at all. Breast cancer adjuvant therapy was widely available in
      the three most recent mammography screening trials, but not the earlier trials.
      Additionally, population-based studies seem to suggest that the benefit of
      mammography screening is diminishing as treatments continue to improve.
      CONCLUSION: Thus, in the years ahead, further declines in breast cancer mortality
      will likely be fueled by advances in therapy, and not by improvements in
      screening technology.

PMID- 21722665
TI  - Very low pandemic influenza A (H1N1) 2009 mortality associated with early
      neuraminidase inhibitor treatment in Japan: analysis of 1000 hospitalized
      children.
AB  - OBJECTIVE: There were many cases of pandemic influenza A (H1N1) 2009 (H1N1/09) in
      Japan during the 2009-2010 epidemic. They accounted for 16% of the total
      population (20.7 million/128 million), and 59% of the patients were children 15
      years of age and under (12.2 million/20.7million). However, there were only 38
      paediatric deaths. We analyzed the clinical manifestations and treatment of
      children hospitalized because of H1N1/09 infection in order to clarify the
      association between treatment with neuraminidase inhibitors and the low mortality
      rate. METHODS: A retrospective chart review was performed on a total of 1000
      paediatric inpatients. RESULTS: The causes of the hospitalizations were
      respiratory complications in 651 cases (65.1%), neurological complications in 255
      cases (25.5%) and other complications in 94 cases. Neuraminidase inhibitors,
      primarily oseltamivir, had been used to treat 984 (98.4%) of the 1000 patients,
      and in 88.9% of the patients, treatment with neuraminidase inhibitors was
      initiated within 48 h after the onset of illness. Only 12 (1.2%) of the 1000
      patients underwent mechanical ventilation, and one patient died of H1N1/09
      infection. CONCLUSIONS: Although a high proportion of the patients in this study
      had severe respiratory complications, the case fatality rate was only 0.1%. The
      low mortality rate of children due to the H1N1/09 epidemic in Japan was probably
      attributable to the universal implementation of early treatment with
      neuraminidase inhibitors.

PMID- 21722666
TI  - A simple model to predict bacteremia in women with acute pyelonephritis.
AB  - OBJECTIVES: To construct a simple model to predict bacteremia in women with
      uncomplicated acute pyelonephritis (APN) for the judicious use of blood cultures.
      METHODS: A prospective database including 735 women with uncomplicated APN at an
      academic urban emergency department was analyzed retrospectively. Independent
      risk factors were determined using multivariate logistic regression in two-thirds
      of patients. Cutoff values representing 10% and 30% of risk were selected for the
      stratification. This model was internally and externally validated using a
      remaining one-thirds of patients and 169 independent patients, respectively.
      RESULTS: Independent risk factors were as follows: age >=65 years (odds ratio
      [OR]=5.18, 4 points), vomiting (OR=2.40, 2 points), heart rate >110 beats/min
      (OR=2.35, 2 points), segmented neutrophils >90% (OR=3.17, 3 points), and urine
      WBC >=50/HPF (OR=4.27, 4 points). Patients were stratified as low (points <4),
      intermediate (points, 4-6), or high risk (7<= points). The areas under receiver
      operating characteristics curves were 0.707 and 0.792 in internal and external
      validation cohorts, respectively. The model stratified internal and external
      validation cohort into low (8.5% and 5.7%), intermediate (16.5% and 14.8%), and
      high risk of bacteremia (42.0% and 56.4%). CONCLUSIONS: This model provides a
      useful tool to predict the risk of bacteremia, which can be helpful to decide
      whether to perform blood cultures and whether to admit the patient for the
      intravenous antibiotics in women with uncomplicated APN.

PMID- 21722667
TI  - Automated EEG analysis: characterizing the posterior dominant rhythm.
AB  - Automated interpretation of clinical EEG recordings will reduce subjectivity and
      visual bias from analysis and can reduce the time required for interpretation. As
      a first step in the design of a fully automated system, a method is presented to
      characterize the main properties of the posterior dominant rhythm (PDR), in
      particular its frequency, symmetry and reactivity. The presented method searches
      for dominant peaks in the EEG spectra during eyes-closed states with a three
      component curve-fitting technique. From the fitted curve, the frequency and
      amplitude are estimated. The symmetry and the reactivity are found using the
      spectral power at the PDR frequencies. In addition, a certainty value is
      introduced as a measure of confidence for each estimate. The method was evaluated
      on a test set of 1215 clinical EEG recordings and compared to the PDR frequencies
      obtained from the visual analysis, as reported in the diagnostic reports. The
      calculated PDR frequencies were within 1.2Hz of the visual estimates in 92.5% of
      the cases. Even higher accuracies were reached when estimates with low certainty
      values were discarded. The presented method quantifies essential features of the
      PDR with a matched accuracy to visual inspection, making it a feasible
      contribution to the design of a fully automated interpretation system.

PMID- 21722668
TI  - Calcineurin subunit B is an immunostimulatory protein and acts as a vaccine
      adjuvant inducing protective cellular and humoral responses against pneumococcal
      infection.
AB  - Protective immunity involves a dynamic balance between humoral and cellular
      immune responses. In the present work we demonstrated that recombinant human
      calcineurin subunit B (rhCnB) stimulated the expression of the surface molecules
      CD83, CD80, CD86, CD40, and HLA-DR. It also promoted secretion of inflammatory
      cytokines IL-6, TNF-alpha, and IL-1beta by human PBMC-derived dendritic cells. In
      in vivo experiments, splenocytes from BALB/c mice immunized with pneumolysin plus
      rhCnB contained a higher percentage of CD3(+)CD4(+) T lymphocytes, produced more
      antigen-specific splenocyte proliferation activity, and had higher anti
      pneumolysin immunoglobulin G (IgG) titers. Transcript levels of cytokines such as
      IL-4, IL-10, and IFN-gamma in the splenocytes were also upregulated when in vitro
      stimulated with pneumolysin. Thus, rhCnB promoted a mixed Th1/Th2 type immune
      response when given together with the specific antigen PN. RhCnB could have
      potential as a prophylactic vaccine adjuvant.

PMID- 21722669
TI  - Inactivation of a non-enveloped RNA virus by artificial ribonucleases: honey bees
      and acute bee paralysis virus as a new experimental model for in vivo antiviral
      activity assessment.
AB  - RNA-containing viruses represent a global threat to the health and wellbeing of
      humans and animals. Hence, the discovery of new approaches for the design of
      novel vaccines and antiviral compounds attains high attention. Here we describe
      the potential of artificial ribonucleases (aRNases), low molecular weight
      compounds capable to cleave phosphodiester bonds in RNA under mild conditions, to
      act as antiviral compounds via destroying the genome of non-enveloped RNA
      viruses, and the potential of utilizing honey bee larvae and adult bees (Apis
      mellifera) as a novel experimental system for the screening of new antiviral
      compounds. Pre-incubation of an Acute bee paralysis virus (ABPV) suspension with
      aRNases D3-12, K-D-1 or Dp12F6 in a concentration-dependent manner increased the
      survival rate of bee larvae and adult bees subsequently infected with these
      preparations, whereas incubation of the virus with aRNases ABL3C3 or L2-3 had no
      effect at all. The results of RT-PCR analysis of viral RNA isolated from aRNase
      treated virus particles confirmed that virus inactivation occurs via degradation
      of viral genomic RNA: dose-dependent inactivation of ABPV correlates well with
      the cleavage of viral RNA. Electron microscopy analysis revealed that the
      morphology of ABPV particles inactivated by aRNases remains unaffected as
      compared to control virus preparations. Altogether the obtained results clearly
      demonstrate the potential of aRNases as a new virus inactivation agents and bee
      larvae/ABPV as a new in vivo system for the screening of antiviral compounds.

PMID- 21722670
TI  - Characterization of the binding affinities of peramivir and oseltamivir
      carboxylate to the neuraminidase enzyme.
AB  - With the continued threat of morbidity and mortality from influenza and the
      development of resistance to influenza antiviral drugs, there is increasing
      interest in new treatments, such as the investigational intravenous drug
      peramivir, and in combination treatments. In this study, we determined the impact
      of oseltamivir carboxylate on the binding affinity of peramivir/neuraminidase
      (NA) enzyme complex and vice versa. Influenza NA was incubated with peramivir and
      oseltamivir carboxylate alone and in combination. Dissociation rates of the
      enzyme-inhibitor complex measured in the presence of NA substrate for peramivir
      alone and the combination were similar, suggesting that peramivir competitively
      inhibits the neuraminidase enzyme and that oseltamivir carboxylate when added to
      peramivir does not impact the binding affinity of peramivir to the NA enzyme.

PMID- 21722671
TI  - The route of immunization with adenoviral vaccine influences the recruitment of
      cytotoxic T lymphocytes in the lung that provide potent protection from influenza
      A virus.
AB  - Virus-specific cytotoxic T lymphocytes (CTLs) in the lung are considered to
      confer protection from respiratory viruses. Several groups demonstrated that the
      route of priming was likely to have an implication for the trafficking of antigen
      specific CTLs. Therefore, we investigated whether the route of immunization with
      adenoviral vaccine influenced the recruitment of virus-specific CTLs in the lung
      that should provide potent protection from influenza A virus. Mice were immunized
      with recombinant adenovirus expressing the matrix (M1) protein of influenza A
      virus via various immunization routes involving intraperitoneal, intranasal,
      intramuscular, or intravenous administration as well as subcutaneous
      administration in the hind hock. We found that the immunization route
      dramatically impacted the recruitment of M1-specific IFN-gamma(+) CD8(+) T cells
      both in the lung and the spleen. Surprisingly, hock immunization was most
      effective for the accumulation in the lung of IFN-gamma-producing CD8(+) T cells
      that possessed M1-specific cytolytic activity. Further, antigen-driven IFN
      gamma(+) CD8(+) T cells in the lung, but not in the spleen, were likely to be
      correlated with the resistance to challenge with influenza A virus. These results
      may improve our ability to design vaccines that target virus-specific CTL
      responses to respiratory viruses such as influenza A virus.

PMID- 21722672
TI  - CK2 inhibitors increase the sensitivity of HSV-1 to interferon-beta.
AB  - Herpes simplex virus type 1 (HSV-1) requires the activities of cellular kinases
      for efficient replication. The host kinase, CK2, has been shown or is predicted
      to modify several HSV-1 proteins and has been proposed to affect one or more
      steps in the viral life cycle. Furthermore, potential cellular and viral
      substrates of CK2 are involved in antiviral pathways and viral counter-defenses,
      respectively, suggesting that CK2 regulates these processes. Consequently, we
      tested whether pharmacological inhibitors of CK2 impaired HSV-1 replication,
      either alone or in combination with the cellular antiviral factor, interferon
      beta (IFN-beta). Our results indicate that the use of CK2 inhibitors results in a
      minor reduction in HSV-1 replication but enhanced the inhibitory effect of IFN
      beta on replication. This effect was dependent on the HSV-1 E3 ubiquitin ligase,
      infected cell protein 0 (ICP0), which impairs several host antiviral responses,
      including that produced by IFN-beta. Inhibitors of CK2 did not, however, impede
      the ability of ICP0 to induce the degradation of two cellular targets: the
      promyelocytic leukemia protein (PML) and the DNA-dependent protein kinase
      catalytic subunit (DNA-PKcs). Notably, this effect was only apparent for HSV-1,
      as the CK2 inhibitors did not enhance the antiviral effect of IFN-beta on either
      vesicular stomatitis virus or adenovirus type 5. Thus, our data suggest that the
      activity of CK2 is required for an early function during viral infection that
      assists the growth of HSV-1 in IFN-beta-treated cells.

PMID- 21722673
TI  - Evaluation of resistance development and viability recovery by a non-enveloped
      virus after repeated cycles of aPDT.
AB  - Nowadays, the emergence of drug resistant microorganisms is a public health
      concern. The antimicrobial photodynamic therapy (aPDT) has an efficient action
      against a wide range of microorganisms and can be viewed as an alternative
      approach for treating microbial infections. The aim of this study was to
      determine if a model target virus (T4-like bacteriophage), in the presence of the
      tricationic porphyrin 5,10,15-tris(1-methylpyridinium-4-yl)-20
      (pentafluorophenyl)porphyrin tri-iodide (Tri-Py(+)-Me-PF), can develop resistance
      to aPDT and recover its viability after photodynamic treatments. To assess the
      development of aPDT resistance after repeated treatments, a suspension of T4-like
      bacteriophage was irradiated with white light (40 Wm(-2)) for 120 min in the
      presence of 5.0 MUM of Tri-Py(+)-Me-PF (99.99% of inactivation) and new phage
      suspensions were produced from the surviving phages, after each cycle of light
      exposure. The procedure was repeated ten times. To evaluate the recovery of viral
      viability after photoinactivation, a suspension of T4-like bacteriophage was
      irradiated with white light for 120 min in the presence of 5.0 MUM of Tri-Py(+)
      Me-PF on five consecutive days. In each day, an aliquot of the irradiated
      suspension was plated and the number of lysis plaques was counted after 24, 48,
      72, 96 and 120 h of dark incubation at 37  degrees C. The profile of
      bacteriophage photoinactivation did not change after ten consecutive cycles and
      no recovery of viability was detected after five accumulated cycles of
      photodynamic treatment. The results suggest that aPDT represents a valuable and
      promising alternative therapy to treat viral infections, overcoming the problem
      of microbial resistance.

PMID- 21722674
TI  - High-throughput screening identification of poliovirus RNA-dependent RNA
      polymerase inhibitors.
AB  - Viral RNA-dependent RNA polymerase (RdRP) enzymes are essential for the
      replication of positive-strand RNA viruses and established targets for the
      development of selective antiviral therapeutics. In this work we have carried out
      a high-throughput screen of 154,267 compounds to identify poliovirus polymerase
      inhibitors using a fluorescence based RNA elongation assay. Screening and
      subsequent validation experiments using kinetic methods and RNA product analysis
      resulted in the identification of seven inhibitors that affect the RNA binding,
      initiation, or elongation activity of the polymerase. X-ray crystallography data
      show clear density for five of the compounds in the active site of the poliovirus
      polymerase elongation complex. The inhibitors occupy the NTP binding site by
      stacking on the priming nucleotide and interacting with the templating base, yet
      competition studies show fairly weak IC50 values in the low MUM range. A
      comparison with nucleotide bound structures suggests that weak binding is likely
      due to the lack of a triphosphate group on the inhibitors. Consequently, the
      inhibitors are primarily effective at blocking polymerase initiation and do not
      effectively compete with NTP binding during processive elongation. These findings
      are discussed in the context of the polymerase elongation complex structure and
      allosteric control of the viral RdRP catalytic cycle.

PMID- 21722675
TI  - Interhemispheric balance sets nostril differences in color-induced nasal thermal
      judgments.
AB  - Sniffing out of sight always the same colorless and odorless solution containing
      no thermal agents while viewing a bottle with colored water increases sensitivity
      of the left nostril/right hemisphere (RH) for warming sensations and sensitivity
      of the right nostril/left hemisphere (LH) for cooling sensations. It is likely
      that engagement in a temperature judgment task and the development of specific
      expectancies due to the presence of color cues alter and enhance processing in
      brain areas involved in thermosensory processing. The lateralized patterns thus
      intimate hemispheric specialization for thermosensory processing probably
      originating in reciprocal inhibition that confers balance between the
      hemispheres. If the inhibition-balance hypothesis were correct then the more the
      left nostril proves sensitive to warming the more the right nostril would prove
      sensitive to cooling. One hundred and ninety one healthy volunteers were tested
      here. The left nostril dominance for warming and the right dominance for cooling
      were replicated once more. The dominance of the left nostril for warming (left
      minus right nostril) correlated highly with the dominance of the left nostril to
      cooling (right minus left nostril) and the individual patterns of results were
      distributed along an axis starting from the expected left nostril/warming - right
      nostril/cooling pattern and ending at the opposite left nostril/cooling - right
      nostril/warming pattern. Furthermore, the point where the left nostril dominance
      for warming responses dropped and inverted perfectly coincided with the point
      where the right nostril dominance for cooling responses inverted too. Such a good
      continuum between the expected and the opposite patterns supports the inhibition
      balance hypothesis. Finally, 66% of subjects exhibited the expected left
      warming/right-cooling pattern suggesting, therefore, that, despite this
      continuum, there is a dominant lateral specialization for temperature processing.

PMID- 21722676
TI  - Diabetes impairs learning performance through affecting membrane excitability of
      hippocampal pyramidal neurons.
AB  - Previous research has demonstrated that diabetes induced learning and memory
      deficits. However, the mechanism of memory impairment induced by diabetes is
      poorly understood. Sprague-Dawley rats were used in the present study to
      investigate the effect of streptozotocin (STZ)-induced diabetes on spatial
      learning and memory with the Morris water maze. The excitability of CA1 pyramidal
      neurons in hippocampus was also examined. Diabetes impaired spatial learning and
      memory of rats. Diabetes decreased the membrane excitability of CA1 pyramidal
      neurons, effects which may contribute to the behavioral deficits. To investigate
      the further ionic mechanisms, the sodium currents and the potassium currents were
      detected. Diabetes decreased both transient and persistent sodium currents, and
      increased both transient and sustained potassium currents, which leads to the
      reduction of neuron excitability and to the increase of firing accommodation. The
      results of the present study suggested that sodium and potassium currents
      contributed to the inhibitory effect of diabetes on neuron excitability, further
      influencing learning and memory processing. Modulating the ion channels and
      increasing the membrane excitability are possible candidates for preventing the
      impairments of diabetes on hippocampal function.

PMID- 21722677
TI  - Molecular and biochemical characterization of nitric oxide synthase isoforms and
      their intracellular distribution in human peripheral blood mononuclear cells.
AB  - Nitric oxide synthase (NOS) expression and catalytic status in human peripheral
      blood mononuclear cells (PBMCs) is debatable, while its sub-cellular distribution
      remains unascertained. The present study characterizes NOS transcripts by real
      time PCR, NOS protein by immunoprecipitation (IP)/Western blot (WB), nitric oxide
      (NO) generation by DAF-2DA and NOS sub-cellular distribution by immunogold
      electron microscopy in resting PBMCs, monocytes and lymphocytes obtained from
      healthy donors. We observed constitutive expression of full length NOS isoforms
      (nNOS, iNOS and eNOS) in PBMCs: with the highest expression of iNOS in comparison
      to nNOS and eNOS. Isolated monocytes expressed more eNOS transcript and protein
      as compared to nNOS and iNOS. Lymphocytes however had more iNOS transcripts and
      protein than nNOS and eNOS. NOS was catalytically active in PBMCs, monocytes as
      well as in lymphocytes as evident by NO generation in the presence of substrate
      and cofactors, which was significantly reduced in the presence of NOS inhibitor.
      Immunogold electron microscopy and morphometric analysis revealed the distinct
      pattern of NOS distribution in monocytes and lymphocytes and also exhibited
      differences in the nuclear-cytoplasmic ratio. nNOS localization was much more in
      the cytosol than in the nucleus among both monocytes and lymphocytes.
      Interestingly, iNOS distribution was comparable in both cytosol and nucleus among
      monocytes, but in lymphocytes iNOS was predominantly localized to the cytosol.
      The present study exhibits constitutive presence of all the NOS isoforms in PBMCs
      and reports the distinct pattern of NOS distribution among monocytes and
      lymphocytes.

PMID- 21722678
TI  - Exploring the dynamics of P300 amplitude in patients with schizophrenia.
AB  - This study investigated the time-frequency dynamics of P300 generation in
      patients with first-onset schizophrenia. A group of 40 patients with first-onset
      schizophrenia and 40 controls performed an auditory oddball task. Wavelet
      analysis of the single-trial data was used to compute the Event-Related Spectral
      Perturbation (ERSP) and the Inter-Trial Phase Coherence (ITC) for the delta,
      theta, alpha, beta and gamma bands on the 50ms window around peak P300 amplitude.
      The contribution of power and synchrony for P300 amplitudes was studied through
      correlation and regression analysis. Further, two sub-samples in which patients
      had lower or higher P300 amplitudes than their control match were contrasted.
      P300 amplitude did not differ between patients and controls. The frequency domain
      analysis revealed that controls display larger reductions on gamma power than
      patients. However, this gamma activity might be the result of micro-saccadic
      muscular artifacts. Regression analysis shows that P300 amplitude is highly
      dependent on delta power and synchronization. The analysis of the subsamples
      confirmed that while gamma power differences are dependent on the diagnosis,
      delta and theta synchronization are related to P300 amplitude, irrespective of
      diagnosis.

PMID- 21722679
TI  - Short amyloid-beta immunogens show strong immunogenicity and avoid stimulating
      pro-inflammatory pathways in bone marrow-derived dendritic cells from C57BL/6J
      mice in vitro.
AB  - Amyloid beta peptide 1-15 (Abeta1-15) and its derivatives have attracted the
      attention of the scientific community as candidate vaccines for Alzheimer's
      disease (AD) immunotherapy. Recent studies suggested that Abeta1-42 modulated the
      immune system by inducing pro-inflammatory dendritic cells (DCs) with reduced
      antigen-presenting function. However, it remains elusive how Abeta1-15 impacts
      DCs function. We therefore investigated the modulation by short Abeta peptides of
      DCs from C57Bl/6J mice. Two new immunogens, a tandem repeat of two-lysine-linked
      Abeta1-15 sequences with or without an addition of a RGD motif, were tested.
      Chemotaxis, endocytosis, antigen presenting function and producing cytokines were
      measured. Both peptides increased migration/endocytosis of immature DCs and MHC
      II molecule expression/alloreactive T cell activation in TNF-alpha-matured DCs.
      In addition, they exhibited decreased production of Th1/Th2 cytokines and pro
      inflammatory cytokines. Overall, the two peptides demonstrated strong
      immunogenicity but did not stimulate pro-inflammatory pathways. These results
      support the use of short Abeta immunogens in AD immunotherapy.

PMID- 21722680
TI  - The action of a synthetic derivative of Met5-enkephalin-Arg6-Phe7 on behavioral
      and endocrine responses.
AB  - The neuroendocrine and behavioral effects of Tyr-D-Ala-Gly-Phe-D-Nle-Arg-Phe
      (DADN), a more stable derivative of the endogenous opiate Met-enkephalin related
      peptide Met(5)-enkephalin-Arg(6)-Phe(7) were investigated in mice. The behavioral
      experiments consisted of monitoring the horizontal (square crossing) and vertical
      (rearing) locomotion in the open field system. To evaluate the effect of the
      heptapeptide on the hypothalamo-pituitary-adrenal (HPA) axis, the plasma
      corticosterone level was measured. DADN induced dose-dependent increases in
      locomotion and rearing 30 min after intracerebroventricular injection and also
      elicited marked activation of the hormonal stress response. To elucidate the
      receptors involved in the mediation of these actions, animals were pretreated
      with the nonselective opioid antagonist naloxone, the selective kappa-receptor
      antagonist nor-binaltorphimine or the MU(1)-receptor blocker naloxonazine. Both
      the HPA activation and the behavioral responses were diminished by the
      preadministration of naloxone. Nor-binaltorphimine did not display a significant
      effect, while naloxonazine completely abolished the hyperactivity and the
      corticosterone elevation elicited by the analog. These findings suggest that MU
      receptors predominate in the mediation of the neuroendocrine actions of DADN,
      while kappa-receptors do not play a significant role.

PMID- 21722681
TI  - Alterations of 3,4-dihydroxyphenylethylamine and its metabolite 3,4
      dihydroxyphenylacetic produced in rat brain tissues after systemic administration
      of saxitoxin.
AB  - We have measured the dopamine levels in some discrete rat brain regions after
      acute intraperitoneal administration of saxitoxin (STX). STX is one of the
      several toxins that causes paralytic shellfish poisoning (PSP). PSP is a serious
      public health concern through the world. Certain dinoflagellates are able of
      producing STX, a powerful neurotoxic compound, which blocks the voltage sensitive
      sodium channels, entailing to the appearance of the main symptoms of poisoning by
      PSP: muscular paralysis and respiratory depression. The goal in this study was to
      analyze the effect of STX on dopamine levels in discrete rat brain regions after
      its acute intraperitoneal administration. Different experimental periods were
      analyzed for STX doses (5 and 10 MUg kg(-1) body weight). With low dose,
      experimental periods were: 30, 60 and 120 min. With high dose, experimental
      period was just 30 min. At the end of each experimental period, animals were
      sacrificed by cervical dislocation. Brains were removed and dissected in:
      hypothalamus, striatum, midbrain, brain stem, right and left hemispheres. This is
      to our knowledge, the first report in which a sublethal dose of STX administered
      intraperitoneally results in an acute alteration of dopamine (DA) production and
      its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC).

PMID- 21722682
TI  - Cellular and humoral immune effector mechanisms required for sterile protection
      against sporozoite challenge induced with the novel malaria vaccine candidate
      CelTOS.
AB  - The malarial protein CelTOS, for cell-traversal protein for ookinetes and
      sporozoites, from Plasmodium berghei has been shown to mediate malarial invasion
      of both vertebrate and insect host cells and is required for establishing their
      successful infections. In the vertebrate host, Plasmodium sporozoites traverse
      via a complex passage through cellular barriers in the skin and the liver
      sinusoid to infect hepatocytes. Induction of immunity targeted to molecules
      involved in sporozoite motility and migration into hepatocytes may lead to
      abrogation of hepatocyte infection. We have previously demonstrated the potential
      of CelTOS as a target antigen for a pre-erythrocytic vaccine. The objective of
      the current study was to determine the potency of different vaccine platforms to
      induce protective immunity and determine the mode of action in protective immune
      responses. To this end, inbred Balb/c and outbred ICR mice were immunized with
      either the recombinant protein adjuvanted with Montanide ISA-720 or with a pCI
      TPA plasmid encoding the P. berghei CelTOS (epidermal delivery by gene-gun) and
      assessed for the induction of protective responses against a homologous P.
      berghei challenge. Humoral and cellular immune responses induced by the various
      immunization regimens were evaluated in an effort to establish immune correlates.
      The results confirm that the CelTOS antigen is a potentially interesting pre
      erythrocytic vaccine candidate and demonstrate that both arms of the adaptive
      immune system are required to mediate complete sterile protection against
      sporozoite challenge.

PMID- 21722683
TI  - Enhanced humoral and cell-mediated immune responses after immunization with
      trivalent influenza vaccine adjuvanted with cationic liposomes.
AB  - The recent pandemic caused by new influenza A (H1N1) has emphasized the need for
      improved influenza vaccines with enhanced immune responses that ideally include
      longlived humoral and CMI responses and mediate a broad protection. This study
      demonstrates that administration of trivalent influenza vaccine (TIV) with the
      cationic liposome adjuvant system CAF01 enhances the humoral immune response as
      measured by hemagglutinin inhibition titers and influenza-specific serum antibody
      titers, and promote a strong Th1 response with augmented levels of IL-1beta, IL
      2, IL-12, IFN-gamma and TNF-alpha. Furthermore, high levels of IL-17 are detected
      in agreement with CAF01's ability to promote TH17 responses. Importantly, the
      Th1/Th17 cytokine profile is still maintained 20 weeks after the last
      vaccination. The CAF01 adjuvanted influenza vaccine reduces weight loss and
      temperature decrease and results in complete survival of mice challenged with the
      drifted H1N1 influenza strain A/PR/8/34. Overall, the results suggest that CAF01
      is a potent adjuvant system for future, improved influenza vaccines.

PMID- 21722684
TI  - Surface antibody and cytokine response to recombinant Chinese hamster ovary cell
      (CHO) hepatitis B vaccine.
AB  - OBJECTIVE: To compare the immune responses of the 10 MUg and 20 MUg doses of CHO
      hepatitis B vaccine on adults. METHODS: Adults aged 18-45 years who gave a
      history of never having received hepatitis B vaccine and lacked serologic
      evidence of infection to hepatitis B virus (HBV) infection or previous
      vaccination were enrolled into the study. A total of 642 eligible participants
      were randomized to receive 3 doses of either the 10 MUg or the 20 MUg formulation
      of CHO hepatitis B vaccine in a 0-1-6 month schedule. Each study subject had a
      serologic specimen collected one month following the third vaccine dose that was
      tested for markers of HBV infection and anti-HBs by Abbott I2000. Persons who
      tested negative for anti-HBs negative persons were tested for HBV DNA. Logistic
      regression was used to identify factors associated with antibody response. Among
      the participants, 153 subjects had their lymphocytes cultivated and tested for
      cytokine production. Enzyme-linked immunospot (ELISPOT) was used to test spot
      numbers of IL-4, IFN-gamma which produced by lymphocyte. RESULTS: The anti-HBs
      seroconversion rate was 88.8% (95% CI: 85.4-92.2%) and 95.3% (95% CI: 93.0
      97.6%), respectively in 10 MUg and 20 MUg group. Geometric mean titers (GMT) were
      173.42 mIU/ml and 585.51 mIU/ml, respectively in 10 MUg and 20 MUg groups.
      Multivariate analysis demonstrated that diabetes, spouse is hepatitis B virus
      infector, older age and receipt of the 10 MUg dose were all negatively associated
      with antibody response (P<.05). Cellular immunity results showed: IL-4 immunity
      spot numbers in 20 MUg group was higher than 10 MUg group. With anti-HBs
      increased, the IL-4 immunity spot numbers increased significantly which had
      significant positive correlation (Spearman coefficient=0.538, P<0.0001). IFN
      gamma spot numbers had no statistical significant between the two groups.
      CONCLUSION: The humoral immunity and cytokines response among the group that
      received the 20 MUg CHO hepatitis B vaccine dose was superior compared to the
      group that received the 10 MUg dose. The 20 MUg dose of CHO hepatitis B vaccine
      should be prioritized for adult vaccination programs in China.

PMID- 21722685
TI  - Immunization of protein HPV16 E7 in fusion with mouse HSP70 inhibits the growth
      of TC-1 cells in tumor bearing mice.
AB  - Human papillomavirus (HPV) 16 is the primary etiologic agent of cervical cancer.
      Most HPV16 therapeutic vaccines target E7 protein which is consistently expressed
      in tumor cells. In this study, we cloned mouse autologous heat shock protein 70
      (mHSP70) gene from mouse liver cells and then expressed mHSP70 and fused HPV16 E7
      mHSP70 (E7 at the N-terminus and mHSP70 at the C-terminus) proteins in E. coli.
      Then we investigated the inhibition of TC-1 cell growth by using the E7
      expressing murine tumor cell line, TC-1, as a model of cervical cancer. In this
      model, mice were immunized with the fusion protein of E7-mHSP70 without any
      adjuvant. The results showed that prophylactic immunization of E7-mHSP70
      protected mice against challenge with TC-1 cells. In addition, therapeutic
      immunization with E7-mHSP70 could inhibit TC-1 tumor growth on lungs. Our study
      demonstrated that immunization with E7-mHSP70 protein without any adjuvant could
      generate anti-tumor effect in mice challenged with TC-1 cells.

PMID- 21722686
TI  - Immunoprotection elicited by an enterovirus type 71 experimental inactivated
      vaccine in mice and rhesus monkeys.
AB  - A number of commonly recognized public health issues are associated with EV71
      infection, including the induction of severe cases of hand-foot-and-mouth disease
      (HFMD). Because of such issues, research and development of EV71 vaccine
      candidates is of growing importance. In the present study, an experimental EV71
      inactivated vaccine was prepared, and its corresponding immunogenicity was
      analyzed. The immune responses and immunoprotective effect induced by the vaccine
      in mice and rhesus monkeys are described, and the two animal models are compared
      to evaluate the potential of assessing the inactivated vaccine's immunogenicity
      in these two species. In addition to assessing the vaccine's efficacy in mice,
      our data further elucidate the significance and value of assessing the
      immunogenicity and immunoprotection of vaccine candidates in rhesus monkeys by
      relying on a range of analyses, including pathological, etiological and lethal
      challenge analyses.

PMID- 21722687
TI  - Hepatitis B immunity and vaccination coverage among young adult males in the Air
      Force in South Brazil.
AB  - We conducted a cross-sectional seroprevalence study to determine hepatitis B
      vaccination coverage and hepatitis B virus (HBV) immunity in a population of
      young adult males. Specifically, the population is comprised of Air Force
      conscripts from the metropolitan region of Florianopolis, Santa Catarina, South
      Brazil, who were born prior to the full implementation of the HBV vaccination
      program. Of the 371 young males surveyed, 90% received at least 1 dose of the
      vaccine and 84% completed the 3-dose schedule. Overall, 57% had positive anti-HBs
      titers. We must continue to vaccinate individuals up to 20 years of age in order
      to guarantee a significant reduction in cases of hepatitis B virus.

PMID- 21722688
TI  - The gold industry standard for risk and cost of drug and vaccine development
      revisited.
AB  - Gold dimensions of pharmaceutical drug development indicate that it takes on
      average 11.9 years, with an investment around US$ 0.8 Billion, to launch one
      product on the market. Furthermore, approximately 22% of the drug candidates
      successfully complete clinical testing. These universally acknowledged
      proportions largely originate from one single, much cited publication; Dimasi et
      al. [5]. However an additional six articles describing new chemical entities
      (NCE) development were identified, which contain little, if any, information on
      vaccines. Published cumulative success rates range from 7% to 78% and investments
      calculations span US$ 0.8 to 1.7 Billion. Obviously this disserves further
      clarification?

PMID- 21722690
TI  - Development of a source-to-outcome model for dietary exposures to insecticide
      residues: an example using chlorpyrifos.
AB  - Probabilistic models of interindividual variation in exposure and response were
      linked to create a source-to-outcome population model. This model was used to
      investigate cholinesterase inhibition from dietary exposures to an insecticide
      (chlorpyrifos) in populations of adults and 3 year old children. A
      physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was
      used to calculate the variation in sensitivity occurring from interindividual
      variability in physiology, metabolism, and physical activity levels. A dietary
      intake model characterizes the variation in dietary insecticide exposures and
      variation in anthropometry in the populations. Published equations were used to
      describe the necessary physiology for each simulated individual based on the
      anthropometry from the dietary intake model. The model of the interindividual
      variation in response to chlorpyrifos was developed by performing a sensitivity
      analysis on the PBPK/PD model to determine the parameters that drive variation in
      pharmacodynamics outcomes (brain and red blood cell acetylcholinesterase
      inhibition). Distributions of interindividual variation were developed for
      parameters with the largest impact; the probabilistic model sampled from these
      distributions. The impact of age and interindividual variation on sensitivity at
      the doses that occur from dietary exposures, typically orders of magnitude lower
      than exposures assessed in toxicological studies, was assessed using the source
      to-outcome model. The resulting simulations demonstrated that metabolic
      detoxification capacity was sufficient to prevent significant brain and red blood
      cell acetylcholinesterase inhibition, even in individuals with the lowest
      detoxification potential. Age-specific pharmacokinetic and pharmacodynamic
      parameters did not predict differences in susceptibility between adults and
      children. In the future, the approach of this case study could be used to assess
      the risks from low level exposures to other chemicals.

PMID- 21722689
TI  - Socioecological influences on community involvement in HIV vaccine research.
AB  - OBJECTIVE: This study investigated socioecological factors influencing HIV
      vaccine research participation among communities living in geographic areas with
      high HIV prevalence and high poverty rates. METHODS: We surveyed a sample of 453
      adults <=18 years from areas of high poverty and high HIV prevalence in metro
      Atlanta and differentiated the effects of individual-, social/organizational-,
      and community-level characteristics on participation in HIV vaccine research via
      multilevel modeling techniques that incorporated questionnaire, program, and
      census data. RESULTS: Models that adjusted for both individual-level covariates
      (such as race, gender, attitudes, and beliefs concerning HIV research),
      social/organizational- and community-level factors such as local HIV prevalence
      rates, revealed that the extent of HIV prevention-related programs and services
      in census tracts contributed to individuals' likelihood of participation in an
      HIV vaccine study. Additionally, neighborhood-based organizations offering HIV
      medical and treatment programs, support groups, and services (e.g., food,
      shelter, and clothing) encourage greater HIV vaccine research participation.
      CONCLUSIONS: The findings support the hypothesis that community-level factors
      facilitate participation in HIV vaccine research independent of both individual-
      and social/organizational-level factors.

PMID- 21722691
TI  - Venlafaxine or a second SSRI: Switching after treatment failure with an SSRI
      among depressed inpatients: a retrospective analysis.
AB  - BACKGROUND: Approximately 50% of patients with major depressive disorder (MDD) do
      not respond after adequate first-line treatment with a selective serotonin
      reuptake inhibitor (SSRI). Special interest is paid to whether specialist level
      inpatient psychiatric care results differ from community studies. AIM: To compare
      switching alternatives after treatment failure with an SSRI; switching to
      venlafaxine (Dexcel Pharma Israel) versus switching to another SSRI in depressed
      inpatients. METHOD: A retrospective register study of inpatients was undertaken
      in a psychiatric tertiary care university center serving an urban catchment area
      in Israel with a population of more than 900,000. RESULTS: A total of 401 MDD
      inpatients were assigned to antidepressant treatment. Of these, 232 records (47
      venlafaxine, 185 SSRI) were included in the analysis. Patients assigned to
      venlafaxine treatment were older (mean age 64.3 +/- 15 years versus 53.6 +/- 17;
      p<0.01) and had more comorbid physical disorders (80% versus 57%; p<0.001). In
      the primary analysis, there was no statistical difference between groups in
      reduction in CGI-S total scores. The secondary end point of achieving a CGI-S
      score of 2 or less (1 = normal, not at all ill or 2 = borderline mentally ill)
      was statistically significantly better for the venlafaxine treated inpatients
      (P=0.02). AEs were reported less than 10% of patients in both groups. CONCLUSION:
      Patients who remain severely depressed following treatment with an SSRI may gain
      benefit from the dual-action drug venlafaxine, rather than switching to another
      SSRI. These findings need to be further supported by prospective studies.

PMID- 21722692
TI  - Evaluation of bioequivalency and toxicological effects of three sources of
      arachidonic acid (ARA) in domestic piglets.
AB  - Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are routinely added to
      infant formula to support growth and development. We evaluated the bioequivalence
      and safety of three ARA-rich oils for potential use in infant formula using the
      neonatal pig model. The primary outcome for bioequivalence was brain accretion of
      ARA and DHA. Days 3-22 of age, domestic pigs were fed one of three formulas, each
      containing ARA at ~0.64% and DHA at ~0.34% total fatty acids (FA). Control diet
      ARA was provided by ARASCO and all diets had DHA from DHASCO (Martek Biosciences
      Corp., Columbia, MD). The experimental diets a1 and a2 provided ARA from Refined
      Arachidonic acid-rich Oil (RAO; Cargill, Inc., Wuhan, China) and SUNTGA40S
      (Nissui, Nippon Suisan Kaisha, Ltd., Tokyo, Japan), respectively. Formula intake
      and growth were similar across all diets, and ARA was bioequivalent across
      treatments in the brain, retina, heart, liver and day 21 RBC. DHA levels in the
      brain, retina and heart were unaffected by diet. Liver sections, clinical
      chemistry, and hematological parameters were normal. We conclude that RAO and
      SUNTGA40S, when added to formula to supply ~0.64% ARA are safe and nutritionally
      bioequivalent to ARASCO in domestic piglets.

PMID- 21722693
TI  - Effects of mixtures of persistent organic pollutants (POPs) derived from cod
      liver oil on H295R steroidogenesis.
AB  - Crude cod liver oil and liver oil supplements are consumed as a source of vitamin
      A, D and polyunsaturated fatty acids; during winter and early pregnancy. Crude
      cod liver oil however constitutes a considerable source of persistent organic
      pollutants (POPs). This paper aimed at characterizing and quantifying the
      influence of POP mixtures extracted from three different steps in the cod liver
      oil industrial process on hormone production and the expression of
      steroidogenesis-related genes in H295R cells. Exposure to extracts from crude cod
      liver oil and from its industrial waste increased progesterone (P4), cortisol
      (Cort), testosterone (T) and estradiol (E2) production; and among others, the
      expression of MC2R, CYP11B1 and HSD3B2 genes. Observed effects after exposure to
      pharmaceutical cod liver oil extract were considerably lower. The type of effects
      on gene expression and hormone production were similar to those induced by
      forskolin and PCBs, the latter being the major contaminants within the extracts.
      Additional research is required to further unveil the mechanisms behind the
      observed steroidogenic effects and to assess whether the potential risk might
      outweigh the potential benefits of crude and processed cod liver oil consumption.

PMID- 21722694
TI  - Evaluation of safety and human tolerance of the oral probiotic Streptococcus
      salivarius K12: a randomized, placebo-controlled, double-blind study.
AB  - Streptococcus salivarius is naturally a predominant member of the human
      oropharynx and the commercial probiotic strain K12 has been consumed for more
      than a decade. The present study examines the health responses of human
      volunteers to oral ingestion of high doses of S. salivarius K12. A randomized
      group of 53 subjects received a dose of 1 * 10(10)cfu S. salivarius K12 (N=25) or
      placebo (N=28) for 28 days, followed by a 28-day wash out period. Blood, urine
      and saliva samples were collected at baseline and following treatment and
      analyzed, while the oral and gastrointestinal tolerance of the subjects to the
      dosing regimen was determined by use of questionnaires. Adverse events (AE)s were
      recorded for both groups. No statistically significant differences between the
      probiotic and placebo treated groups were detected in either the blood clinical
      chemistry or hematology results (P>0.05). The questionnaire responses of the
      subjects indicated that both treatments were well tolerated. The frequency and
      intensity of AEs was similar in the two groups. This data demonstrates that the
      daily ingestion of S. salivarius K12 over a 28-day period does not adversely
      affect the human host and supports the safety of its oral delivery in a food
      based carrier.

PMID- 21722695
TI  - In vitro and in vivo genotoxic effects of somatic cell nuclear transfer cloned
      cattle meat.
AB  - Although the nutritional composition and health status after consumption of the
      meat and milk derived from both conventionally bred (normal) and somatic cell
      nuclear transferred (cloned) animals and their progeny are not different, little
      is known about their food safeties like genetic toxicity. This study is performed
      to examine both in vitro (bacterial mutation and chromosome aberration) and in
      vivo (micronucleus) genotoxicity studies of cloned cattle meat. The
      concentrations of both normal and cloned cattle meat extracts (0-10*) were tested
      to five strains of bacteria (Salmonella typhimurium: TA98, TA100, TA1535, and
      TA1537; Escherichia coli: WP2uvrA) for bacterial mutation and to Chinese hamster
      lung (CHL/IU) cells for chromosome aberration, respectively. For micronucleus
      test, ICR mice were divided into five dietary groups: commercial pellets
      (control), pellets containing 5% (N-5) and 10% (N-10) normal cattle meat, and
      pellets containing 5% (C-5) and 10% (C-10) cloned cattle meat. No test substance
      related genotoxicity was noted in the five bacterial strains, CHL/IU cells, or
      mouse bone marrow cells, suggesting that the cloned cattle meat potentially may
      be safe in terms of mutagenic hazards. Thus, it can be postulated that the cloned
      cattle meat do not induce any harmful genotoxic effects in vitro and in vivo.

PMID- 21722696
TI  - Polycyclic aromatic hydrocarbons incidence in Portuguese traditional smoked meat
      products.
AB  - Meat and meat products safety is, nowadays, a priority quality requirement with
      chemical hazards having a great impact. Amongst the residues and contaminants,
      polycyclic aromatic hydrocarbons (PAHs) can be of particular concern, namely in
      those products having direct smoking during processing. In order to investigate
      the contamination levels in traditional dry fermented sausages manufactured in
      Alentejo (South of Portugal), 66 samples were collected from regional producers.
      PAH8 represented less than 0.5% of the total contamination profile, with
      benzo[a]anthracene and chrysene being the most concentrated compounds (maximum
      contents of 7.53 and 8.9 MUgkg(-1)), irrespective of the product type analysed.
      Benzo[a]pyrene content varied between 0.21 and 1.00 MUgkg(-1), with only one
      sample showing this maximum content. Blood sausages were potentially more risky,
      since total PAH8 contents were generally higher and because its presence in inner
      parts were significantly superior than that found in casings, comparatively to
      meat counterparts, which expressed superior benzo[a]pyrene toxic equivalents.

PMID- 21722697
TI  - Concentration dependent effects of tobacco particulates from different types of
      cigarettes on expression of drug metabolizing proteins, and benzo(a)pyrene
      metabolism in primary normal human oral epithelial cells.
AB  - The ability of tobacco smoke (TS) to modulate phase I and II enzymes and affect
      metabolism of tobacco carcinogens is likely an important factor in its
      carcinogenicity. For the first time several types of TS particulates (TSP) were
      compared in different primary cultured human oral epithelial cells (NOE) for
      their abilities to affect metabolism of the tobacco carcinogen, (BaP) to
      genotoxic products, and expression of drug metabolizing enzymes. TSP from,
      reference filtered (2RF4), mentholated (MS), reference unfiltered, (IR3), ultra
      low tar (UL), and cigarettes that primarily heat tobacco (ECL) were tested. Cells
      pretreated with TSP concentrations of 0.2-10 MUg/ml generally showed increased
      rates of BaP metabolism; those treated with TSP concentrations above 10 MUg/ml
      showed decreased rates. Effects of TSPs were similar when expressed on a weight
      basis. Weights of TSP/cigarette varied in the order: MS~IR3>2RF4>ECL>UL. All TSPs
      induced the phase I proteins, cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1),
      phase II proteins, NAD(P)H dehydrogenase quinone 1 (NQO1), and microsomal
      glutathione S-transferase 1 (MGST1), and additionally, hydroxysteroid (17-beta)
      dehydrogenase 2 (HSD17B2), as assessed by qRT-PCR. The pattern of gene induction
      at probable physiological levels favored activation over detoxification.

PMID- 21722698
TI  - Modulation of the effects of methylmercury on rat neurodevelopment by co-exposure
      with Labrador Tea (Rhododendron tomentosum ssp. subarcticum).
AB  - Seafood is an important source of nutrients for many populations worldwide.
      Unfortunately the contamination of seafood with methylmercury (MeHg) has raised
      health concerns, particularly for developing infants. The modification of MeHg
      toxicity by nutrients, including antioxidants, has been reported in both
      epidemiological and animal exposure studies. We used a rat perinatal exposure
      model to investigate the modulation of developmental MeHg toxicity by an extract
      of Rhododendron tomentosum ssp. subarcticum, a plant rich in antioxidants
      traditionally consumed by Inuit. Sprague-Dawley rat dams were exposed daily to 2
      mg MeHg/kg bw and 100 mg R. tomemtosum extract/kg bw administered either
      separately or jointly, from the first day of gestation until weaning. MeHg
      exposure was associated with impaired pup growth and survival, decreased grip
      strength, hyperactivity and altered exploratory behaviour, delayed acoustic
      startle response, elevated brain N-methyl-D-aspartate receptor (NMDA-R) levels,
      and increased serum lipid peroxidation. R. tomemtosum extract co-exposure
      modulated MeHg's effects on oxidative stress and brain NMDA-R levels and may have
      affected MeHg pharmacokinetic. However, modulation of these molecular endpoints
      did not lead to significant alterations of MeHg's effects on rat neurobehaviour.

PMID- 21722699
TI  - Haematological and immunological effects of repeated dose exposure of rats to
      integerrimine N-oxide from Senecio brasiliensis.
AB  - This study is the first in the literature to focus attention on the possible
      immunotoxic effect of integerrimine N-oxide content in the butanolic residue (BR)
      of Senecio brasiliensis, a poisonous hepatotoxic plant that contains
      pyrrolizidine alkaloids (PAs). PAs have been reported as a pasture and food
      contaminant and as herbal medicine used worldwide and are responsible for
      poisoning events in livestock and human beings. After the plant extraction, BR
      extracted from Senecio brasiliensis was found to contain approximately 70%
      integerrimine N-oxide by elemental and spectral analyses ((1)H and (13)C NMR),
      which was administered to adult male Wistar Hannover rats at doses of 3, 6 and 9
      mg/kg for 28 days. Body weight gain, food consumption, lymphoid organs,
      neutrophil analysis, humoural immune response, cellular immune response and
      lymphocyte analysis were evaluated. Our study showed that integerrimine N-oxide
      could promote an impairment in the body weight gain, interference with blood cell
      counts and a reducing T cell proliferative activity in rats; however, no
      differences in the neutrophil activities, lymphocytes phenotyping and humoural
      and cellular immune responses were observed. It is concluded that doses of
      integerrimine N-oxide here employed did not produce marked immunotoxic effects.

PMID- 21722700
TI  - Validation of an LDH assay for assessing nanoparticle toxicity.
AB  - Studies showed that certain cytotoxicity assays were not suitable for assessing
      nanoparticle (NP) toxicity. We evaluated a lactate dehydrogenase (LDH) assay for
      assessing copper (Cu-40, 40nm), silver (Ag-35, 35nm; Ag-40, 40nm), and titanium
      dioxide (TiO(2)-25, 25nm) NPs by examining their potential to inactivate LDH and
      interference with beta-nicotinamide adenine dinucleotide (NADH), a substrate for
      the assay. We also performed a dissolution assay for some of the NPs. We found
      that the copper NPs, because of their high dissolution rate, could interfere with
      the LDH assay by inactivating LDH. Ag-35 could also inactivate LDH probably
      because of the carbon matrix used to cage the particles during synthesis. TiO(2)
      25 NPs were found to adsorb LDH molecules. In conclusion, NP interference with
      the LDH assay depends on the type of NPs and the suitability of the assay for
      assessing NP toxicity should be examined case by case.

PMID- 21722701
TI  - Augmentation of myelopoiesis in a murine host bearing a T cell lymphoma following
      in vivo administration of proton pump inhibitor pantoprazole.
AB  - Proton pump inhibitors (PPI) are being proposed as potent antitumor agents, owing
      to their ability to specifically induce tumor cell death by reversing H(+) ion
      homeostasis. As tumor growth induces myelosuppression in tumor-bearing hosts, it
      remains unclear if PPI can also modulate tumor-induced myelosuppression. Thus, we
      studied the effect of in vivo administration of pantoprazole (PPZ), a PPI, on
      myelopoiesis in a murine model of a transplantable T cell lymphoma, designated as
      Dalton's lymphoma (DL). Intraperitoneal administration of PPZ to tumor-bearing
      mice resulted in an enhanced bone marrow cellularity, inhibited induction of
      apoptosis and augmented bone marrow cell (BMC) survival. BMC of PPZ-administered
      tumor-bearing mice showed elevated number of F4/80 positive cells, augmented
      colony forming ability and differentiation in bone marrow-derived macrophages
      (BMDM) with higher expression of F4/80 and CD11c markers. This study also
      presents evidences to indicate that PPZ-dependent augmentation of myelopoiesis in
      the tumor-bearing host is dependent on an enhanced expression of M-CSF and
      receptors for M-CSF & GM-CSF in BMC, along with a modulation in the expression of
      cell survival regulatory molecules PUMA, Bcl2, p53 and caspase-activated DNase
      (CAD). BMDM obtained from PPZ-administered tumor-bearing mice also showed an
      augmented expression of TLR-2, tumoricidal activity, production of NO and
      monokines: IL-1, IL-6 & TNF-alpha. The study discusses the possible mechanisms
      underlying PPZ-dependent augmentation of myelopoiesis. Taken together, the
      present study proposes that a PPZ-dependent alleviation of tumor-induced
      myelosuppression could contribute to an augmented myelopoiesis.

PMID- 21722702
TI  - The can and can't dos of p53 RNA.
AB  - The p53 protein, like any other protein, cannot be made in the cell without RNA.
      And even once made, the p53 protein will be more rapidly degraded without the p53
      RNA. Furthermore, the p53 RNA helps deciding which p53 isoform should be produced
      and under which cell conditions. Mutant p53 mRNA codes for an unstable and
      inactive protein. These matters are discussed in this article as well as the
      recent reports on p53 RNA mutations, interacting-proteins, 3' processing and 5'
      3' loop.

PMID- 21722703
TI  - Functional magnetic resonance imaging as a dynamic candidate biomarker for
      Alzheimer's disease.
AB  - During the last two decades, imaging of neural activation has become an
      invaluable tool for assessing the functional organization of the human brain in
      vivo. Due to its widespread application in neuroscience, functional neuroimaging
      has raised the interest of clinical researchers in its possible use as a
      diagnostic biomarker. A hallmark feature of many neurodegenerative diseases is
      their chronic non-linear dynamic and highly complex preclinical course.
      Neurodegenerative diseases unfold over years to decades through clinically silent
      and asymptomatic stages of early adaptive, compensatory to pathophysiological
      (i.e. actively neurodegenerative) and decompensatory mechanisms in the brain -
      phases that are increasingly being considered as critical for primary and
      secondary preventive and therapeutic measures. Emerging evidence supports the
      concept of a potentially fully reversible functional phase that may precede the
      onset of micro- and macrostructural and cognitive decline, a potentially late
      stage "neurodegenerative" phase of a primary neurodegenerative disorder.
      Alzheimer's disease serves as an ideal model to test this hypothesis supported by
      the neural network model of the healthy and diseased brain. Being highly dynamic
      in nature, brain activation and neuronal network functional connectivity
      represent not only candidate diagnostic but also candidate surrogate markers for
      interventional trials. Potential caveats of functional imaging are critically
      reviewed with focus on confound variables such as altered neurovascular coupling
      as well as parameters related to task- and study design.

PMID- 21722704
TI  - Inhibins and activins: their roles in the adrenal gland and the development of
      adrenocortical tumors.
AB  - The adrenal gland is composed of two separate endocrine tissues that control a
      multitude of bodily functions in their adaptation to external and internal
      stressors through hormone secretion. The functions of the adrenal gland are
      regulated by circulating, neural and local factors that ensure proper cell growth
      and hormone production. Activins and inhibins are among the locally expressed
      growth factors affecting adrenal cell function. They have been found to influence
      several aspects of adrenal cell development, adrenocortical steroidogenesis,
      adrenocortical tumor formation and adrenomedullary cell differentiation.
      Especially the finding that inhibin alpha-subunit knockout mice develop
      adrenocortical carcinomas after gonadectomy has prompted research on the
      physiological and pathophysiological roles of activin and inhibin in the adrenal
      cortex. It is now clear that both peptides control adrenocortical physiology and
      are involved in adrenocortical tumorigenesis at multiple levels, both in murine
      models as well as in human patients.

PMID- 21722705
TI  - A needle in a haystack: mutations in GNRH1 as a rare cause of isolated GnRH
      deficiency.
AB  - GNRH1, the human gene that gives rise to GnRH, has long been an obvious candidate
      gene for idiopathic hypogonadotropic hypogonadism, particularly because the hpg
      mouse, a mouse model of isolated hypogonadotropic hypogonadism, carries a
      deletion that disrupts Gnrh1. In 2009, 25 years after the sequence of human GNRH1
      was initially determined, two groups independently reported homozygous frameshift
      mutations in GNRH1 in patients with idiopathic hypogonadotropic hypogonadism. In
      two additional families, heterozygous GNRH1 mutations segregated with
      reproductive disorders. In the first family, the mutation occurred alone in five
      female subjects with idiopathic hypogonadotropic hypogonadism, whereas in the
      second it co-existed with a mutation in NR0B1/DAX1 in two female subjects with
      delayed puberty. While hemizygous mutations the X-linked NR0B1 are a well-known
      cause of hypogonadotropic hypogonadism and adrenal hypoplasia in male patients,
      heterozygous female carriers are generally asymptomatic. Thus, mutations in GNRH1
      have been associated with both mild and severe forms of GnRH deficiency, and may
      work in combination with other gene mutations to produce GnRH-deficient
      phenotypes.

PMID- 21722706
TI  - Interaction between sex hormones and WNT/beta-catenin signal transduction in
      endometrial physiology and disease.
AB  - Wnt/beta-catenin signalling plays a rate-limiting role in early development of
      many different organs in a broad spectrum of organisms. In the developing
      Mullerian duct, Wnt/beta-catenin signalling is important for initiation,
      outgrowth, patterning and differentiation into vagina, cervix, uterus and
      oviducts. In adult life, sex hormones modulate Wnt/beta-catenin signalling in the
      endometrium to maintain the monthly balance between estrogen-induced
      proliferation and progesterone-induced differentiation, and enhanced Wnt/beta
      catenin signalling seems to be involved in endometrial carcinogenesis. However,
      early in pregnancy enhanced Wnt/beta-catenin signalling is prerequisite for
      proper implantation and invasion of trophoblast cells into endometrium and
      myometrium thus helping to form a placenta. Overall, it seems that tight control
      of Wnt/beta-catenin signalling in time and space is important for initiation,
      development and normal function of the female reproductive tract. However, if
      Wnt/beta-catenin signalling is not kept in check, it easily seems to initiate or
      contribute to development of a number of uterine disorders.

PMID- 21722707
TI  - Blood pressure increased dramatically in hypertensive rats after left hemisphere
      lesions with 6-hydroxydopamine.
AB  - Plasma angiotensinase activity, nitric oxide and systolic blood pressure (SBP)
      were differently affected after unilateral intrastriatal injection of 6
      hydroxydopamine (6-OHDA), depending on the brain hemisphere injured. Moreover,
      normotensive and hypertensive rats responded differently suggesting an asymmetry
      in the organization of the autonomic nervous system of the vessels. The aim of
      this study was to investigate the evolution of SBP and heart rate (HR) over time
      after nigrostriatal lesions in normotensive and hypertensive rat strains.
      Unilateral depletions of brain dopamine were performed by injecting 6-OHDA into
      the left or right striatum of normotensive and hypertensive rats. Vehicle without
      6-OHDA was unilaterally injected in control (sham) groups. SBP and heart rate
      (HR) were measured in un-anesthetised animals 10 and 3 days before administration
      of 6-OHDA or vehicle and 3 and 25 days after treatment. In normotensive rats, at
      the end of study, SBP increased significantly from pre-lesioned values in left
      lesioned animals but no differences were observed in right-lesioned or sham
      groups. Before sacrifice, there was a significant reduction from pre-lesion
      values in HR. In hypertensive animals, there was a highly significant increase of
      SBP in left-lesioned and sham left rats and a slight increase in right-lesioned
      but no differences were observed in sham right group. No differences in HR were
      observed throughout the study in the groups studied. The present results
      represent direct experimental evidence of an asymmetrical cardiovascular response
      to unilateral brain lesions, suggesting that left injury may have a worst
      prognosis.

PMID- 21722708
TI  - Insomnia, platelet serotonin and platelet monoamine oxidase in chronic
      alcoholism.
AB  - Insomnia is a common sleep disorder frequently occurring in chronic alcoholic
      patients. Neurobiological basis of insomnia, as well as of alcoholism, is
      associated with disrupted functions of the main neurotransmitter systems,
      including the serotonin (5-hydroxytryptamine, 5-HT) system. Blood platelets are
      considered a limited peripheral model for the central 5-HT neurons, since both
      platelets and central 5-HT synaptosomes have similar dynamics of 5-HT. Platelet 5
      HT concentration and platelet monoamine oxidase type B (MAO-B) are assumed to
      represent biomarkers for particular symptoms and behaviors in psychiatric
      disorders. The hypothesis of this study was that platelet 5-HT concentration and
      platelet MAO-B activity will be altered in chronic alcoholic patients with
      insomnia compared to comparable values in patients without insomnia. The study
      included 498 subjects: 395 male and 103 female medication-free patients with
      alcohol dependence and 502 healthy control subjects: 325 men and 177 women. The
      effects of early, middle and late insomnia (evaluated using the Hamilton
      Depression Rating Scale), as well as sex, age and smoking on platelet 5-HT
      concentration and platelet MAO-B activity were evaluated using one-way ANOVA and
      multiple regression analysis by the stepwise method. Platelet 5-HT concentration,
      but not platelet MAO-B activity, was significantly reduced in alcoholic patients
      with insomnia compared to patients without insomnia. Multiple regression analysis
      revealed that platelet 5-HT concentration was affected by middle insomnia,
      smoking and sex, while platelet MAO activity was affected only by sex and age.
      The present and previous data suggest that platelet 5-HT concentration might be
      used, after controlling for sex and smoking, as a biomarker for insomnia in
      alcoholism, PTSD and in rotating shift workers.

PMID- 21722709
TI  - Pre-screening and follow-up of childhood acute leukemia using biochemical
      infrared analysis of peripheral blood mononuclear cells.
AB  - BACKGROUND: Recent advances in chemotherapeutic treatment of childhood acute
      leukemia have improved remission rates to about 80%. With the development of
      novel drugs and treatment protocols adapted for specific individual patients, a
      simple diagnostic tool for following patients' responses on a daily basis is
      required. In the present clinical study, we have investigated the usefulness of
      Fourier transform infrared microscopy (FTIR-MSP) for pre-screening and follow-up
      of leukemia patients undergoing chemotherapy. METHODS: Blood samples were
      collected from leukemia patients before and during treatment as well as from
      patients with high fever and healthy subjects which served as control groups.
      Peripheral blood mononuclear cells (PBMCs) were isolated and their spectra
      obtained using FTIR-MSP. The presence of blasts in bone marrow and other
      diagnostic and prognostic clinical parameters were determined during follow-up up
      to 1000 days. RESULTS: Leukemia was efficiently indicated by a reduced lipids and
      elevated DNA absorption of PBMC together with additional characteristic spectral
      bands. These diagnostic markers were used for monitoring the biochemical changes
      in PBMCs during chemotherapy. The trends of several markers were found to be in
      agreement with blast percentage as determined by flow cytometry. CONCLUSIONS: Our
      findings reveal the utility of FTIR-MSP for leukemia pre-screening independently
      of symptoms common to leukemia. Furthermore, FTIR-MSP supplies precursor
      indication regarding patient response to treatment compared to current methods.
      GENERAL SIGNIFICANCE: This preliminary study shows a great potential of FTIR-MSP
      as a complementary tool for childhood leukemia pre-screening and follow-up which
      may allow faster response to critical problems arise during treatment.

PMID- 21722710
TI  - Age-dependent regulation of depression-like behaviors through modulation of
      adrenergic receptor alpha1A subtype expression revealed by the analysis of
      interleukin-1 receptor antagonist knockout mice.
AB  - Interleukin-1 (IL-1) plays a crucial role in stress responses and its mRNA is
      induced in the brain by stress load; however, the precise role of IL-1 in higher
      brain functions and their abnormalities is largely unknown. Here, we report that
      IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lack IL-1Ra molecules
      that antagonize the IL-1 receptor, displayed anti-depression-like phenotypes in
      the tail suspension test (TST) and forced-swim test (FST) only at a young stage
      (8 weeks), whereas the phenotypes disappeared at later stages (20 and 32 weeks).
      These anti-depression-like phenotypes were reversed by administration of
      adrenergic receptor (AR) antagonists against the ARalpha(1), ARalpha(2), and
      ARbeta subtypes. Although the contents of 5-HT, norepinephrine (NE), and dopamine
      (DA), which are known to be associated with major symptoms of psychiatric
      disorders, were not significantly different in the hippocampus or cerebral cortex
      between IL-1Ra KO and their wild-type (WT) littermate mice, the mRNA expression
      level of the ARalpha(1A) subtype was significantly changed in the cerebral
      cortex. Interestingly, the change in expression of the ARalpha(1A) subtype was
      correlated with an age-dependent alteration in the TST and FST in IL-1Ra KO mice.
      Furthermore, mild immobilization stress loaded on C57BL/6J male mice caused
      similar anti-depression-like phenotypes in the TST and FST to those observed in
      mutant mice. These results suggest that sustained activation of IL-1 signaling
      induced by gene manipulation in mutant mice affects the expression of the
      ARalpha(1A) subtype and that modification of adrenergic signaling by the IL-1
      system may ultimately cause significant psychiatric abnormalities such as
      depression, and this mutant mouse could be regarded as a model animal of
      depression that specifically appears in children and adolescents.

PMID- 21722711
TI  - Semantic association of ecologically unrelated synchronous audio-visual
      information in cognitive integration: an event-related potential study.
AB  - In this paper, we aimed to study the semantic association of ecologically
      unrelated synchronous audio-visual information in cognitive integration. A moving
      particle, which speed varied, was taken as a visual stimulus, while a simple
      tone, which frequency varied, was used as an auditory stimulus, both were
      synchronously presented to subjects in the form of a video. Behavioral results
      confirmed our hypothesis that the moving particle with varied speed and the
      simple tone with varied frequency were highly associated. Event-related potential
      (ERP) results showed that an N400 effect and a late posterior negativity (LPN)
      were elicited under the Incongruent condition as compared to the Congruent
      condition. It was further determined that there was semantic association between
      ecologically unrelated synchronous audio-visual information in cognitive
      integration. We considered that the N400 effect in our results reflected the
      process that stimulus-driven activities are bound together through a temporal
      semantic network (TSN) to form multimodal representations, while the state of
      this temporal semantic network was determined by both long-term learned
      association among stimuli and short-term experience of incoming information. The
      LPN might reflect the process that the human brain searches and retrieves context
      specifying information in order to make a judgment, and the context-specifying
      information might have originated from the long-term learned association stored
      in the brain.

PMID- 21722712
TI  - Reduced neurogenesis and pre-synaptic dysfunction in the olfactory bulb of a rat
      model of depression.
AB  - A variety of evidence has a connection with hippocampal neurogenesis in the
      pathophysiology of depression. However, whether other neurogenic regions in the
      adult central nervous system would likewise be involved is a highly interesting
      question. The olfactory bulb (OB) is one of the post-developmental neurogenesis
      areas in the adult mammalian brain. Clinical studies have shown a decreased
      olfactory sensitivity in depressed patients, and a recent study disclosed cases
      of reduced OB volume in acute major depression, indicating the OB may be also
      affected. Here, animal models are superior to human studies, which may provide
      further insight into such complex processes. We therefore investigated OB
      neurogenesis using a chronic unpredictable mild stress (CUMS) rat model of
      depression. Considering the functional analysis of adult neurogenesis which has
      been carried out at the synaptic level as well as animal behavior level, we
      detected pre-synaptic and olfactory function in the OB of rats after 4 weeks of
      chronic stress. Immunohistochemistry and Western blot analysis showed a dramatic
      reduction of immature neurons marked by polysialylated neural cell adhesion
      molecule and doublecortin as well as mature neurons labeled by neuronal nuclei.
      Moreover, chronic stress down-regulated the expression of synaptophsin but up
      regulated syntaxin in the OB, as demonstrated by Western blot, whereas a
      significant variation at the mRNA level was lacking. Notably, in the rat model of
      depression, both a decreased OB volume and olfactory dysfunction were present at
      the same time, which is consistent with clinical findings in depressed patients.
      In summary, reduced OB neurogenesis and pre-synaptic dysfunction were observed in
      the rat model, which may at least in part correspond to the reduced OB volume and
      olfactory malfunction in patients suffering from depression.

PMID- 21722713
TI  - Hippocampal neuronal death induced by kainic acid and restraint stress is
      suppressed by exercise.
AB  - The present study investigated whether chronic exercise suppressed hippocampal
      neuronal death due to repeated stress followed by i.c.v. kainic acid (KA)
      injection, and whether cAMP response element-binding protein (CREB), mitogen
      activated protein kinase (MAPKs), and calcium/calmodulin-dependent protein kinase
      II (CaMKII) activation contributed to the neuroprotective effect in this
      experimental paradigm. To achieve the objective, mice were subjected to treadmill
      running for 8 weeks (19 m/min, 1 h/d, 5 d/wk) followed by seven consecutive days
      of repeated restraint stress (2 h/d), and then i.c.v. injection of KA (0.05 MUg/5
      MUL). Hippocampal neuronal death was assessed using Nissl staining, and protein
      levels were measured using Western blot and immunohistochemical analysis.
      Hippocampal neuronal loss in mice subjected to restraint stress and KA injection
      was exacerbated compared with KA injection alone, which was reversed in the
      hippocampal CA3 region with prior chronic exercise. To further identify the
      neuroprotective effects of chronic exercise administration on hippocampal insults
      by repeated stress, levels of stress-related factors were measured. First, there
      was no significant difference in serum corticosterone and glucocorticoid (Gc)
      receptor levels in mice with restraint alone and restraint combined with prior
      chronic exercise. Second, malondialdehyde (MDA) and nitrite levels were
      significantly enhanced in restrained mice and were revered in restraint with
      chronic exercise. However, pCREB levels in the hippocampus in restraint mice with
      chronic exercise were profoundly increased compared with levels in restraint
      alone mice. Among the MAPKs, pERK1/2 levels in restraint mice with chronic
      exercise were significantly higher than levels in mice with restraint alone.
      Furthermore, pCaMKII levels in restraint mice with chronic exercise were markedly
      elevated compared with levels in mice after restraint alone. Prior chronic
      exercise suppressed KA-induced hippocampal neuronal death in hippocampal CA3
      region in restrained mice via declined ROS levels, which was lower MDA and
      nitrite levels, and activation of CREB, which was mediated by ERK1/2 and CaMKII,
      suggesting that chronic exercise exerts a protective effect on excitatory
      neurodegenerative disorders including epileptic seizure.

PMID- 21722714
TI  - Fingerprint of Biomphalaria arabica, the intermediate host of Schistosoma mansoni
      in Saudi Arabia, using RAPD-PCR.
AB  - In the time schistosomisis control programs are implemented in many countries,
      schistosomiasis continues to spread throughout the world. Among these control
      strategies is the vector control. Within this context, analysis of the genetic
      variability of the intermediate host snails is important because it allows
      identification of specific sequences of the genome of this mollusk related to
      determine their fingerprint. We investigated Biomphalaria arabica, which is found
      in Saudi Arabia, the intermediate host of Schistosoma mansoni infection. Genetic
      fingerprint was studied by RAPD-PCR using our own different random primers as
      well as published primers. The electrophoretic patterns resulting from
      amplification showed specific polymorphic markers of B. arabica. This information
      will be helpful in the identification of the snails and demonstrating that RAPD
      PCR is an appropriate and efficient methodological approach for establishment of
      genetic barcode development.

PMID- 21722715
TI  - Optimized protocols and plasmids for in vivo cloning in yeast.
AB  - Saccharomyces cerevisiae has proven a valuable system for the construction of
      plasmids via gap repair or in vivo cloning. The method allows cloning with
      superior accuracy and without the need to use restriction enzymes. However,
      despite its remarkable efficiency, the process may occasionally require the
      screening of large number of candidates. We have previously reported that by
      simply using shuttle plasmids that allow blue/white selection in Escherichia
      coli, it is possible to pre-select for positive clones. Here, we demonstrate that
      the same strategy can be used to assemble plasmids from several ectopic DNA
      fragments, which are all introduced in yeast cells by a simple transformation
      step. Further, to facilitate the subcloning of the fragment cloned into other
      targeting or expression vectors, the multi-cloning sites of three shuttle
      plasmids have been extended to include fifteen new restriction enzyme recognition
      sites.

PMID- 21722716
TI  - Molecular structure, expression analysis and functional characterization of APRIL
      (TNFSF 13) in goat (Capra hircus).
AB  - A proliferation-inducing ligand (APRIL) is an important member of the tumor
      necrosis factor (TNF) superfamily. In the present study, a novel cDNA was
      isolated from the spleen of goat by RT-PCR and designated as goat APRIL (gAPRIL).
      The open reading frame (ORF) of this cDNA covered 753bp, encoding a protein of
      250 amino acids. Sequence comparison showed that gAPRIL contains a predicted
      transmembrane domain, a putative furin protease cleavage site, and two cysteine
      residues, which are the typical characteristics of TNF gene in mammals. The
      predicted three dimensional (3D) structure of soluble part of the gAPRIL
      (gsAPRIL) monomer analyzed by comparative protein modeling revealed that it is
      very similar to its counterparts. Real-time PCR analysis revealed that gAPRIL was
      constitutively expressed in various tissues. Recombinant gsAPRIL fused with NusA
      tag was efficiently produced in Escherichia coli BL21 (DE3) and then analyzed by
      the SDS-PAGE as well as western blot. Laser scanning confocal microscopy analysis
      showed gsAPRIL could bind to its receptors. In vitro, the MTT and flow cytometric
      methods revealed that purified gsAPRIL protein was not only able to promote
      survival/proliferation of goat splenocytes, but also able to stimulate
      survival/proliferation of mouse B cells. These results indicated that gAPRIL
      plays an important role in survival/proliferation of goat splenocytes and
      provided a basis for investigating its potential to be used as an immunoadjuvant
      for enhancing vaccine efficacy and as an immunotherapeutic in goats.

PMID- 21722717
TI  - Identification of differentially expressed genes in three-pistil mutation in
      wheat using annealing control primer system.
AB  - The common wheat line three-pistil (TP) is a valuable mutant for wheat breeding.
      The TP mutation has normal spike morphology; however, it only produces three
      pistils per floret. Therefore, it has potential to increase the grain number per
      spike. In order to determine the underlying molecular mechanism, an annealing
      control primer system was used to identify the different expressed genes in three
      pistil mutation. Using 120 arbitrary ACP primers, we identified three
      differentially expressed genes in young spikes between two near-isogenic lines
      (i.e., Chuanmai 28 TP and Chinese Spring TP) and their recurrent parents. We
      tentatively designated the three differentially expressed genes as DETP-1, DETP
      2, and DETP-3. DETP-1 showed similar function with maize cytoplasmic membrane
      protein, which is involved in cell division in bacteria. DETP-3 is homologous to
      maize endo-1, 4-beta-glucanase (EGases), which is associated with plant
      development, cell wall loosening, stem flowering, and root expansion. DETP-2
      showed no significant hit with any sequence found in the database and translates
      unknown protein. These genes would likely play an important role in determining
      the three pistils trait in wheat.

PMID- 21722718
TI  - Molecular cloning and polymorphism analysis of the prion protein gene in Tan
      sheep of Ningxia, China.
AB  - The resistance or susceptibility of sheep to scrapie is associated with
      polymorphisms of the prion protein gene (PRNP), particularly, single nucleotide
      polymorphisms (SNPs) in amino acid positions 136, 154 and 171. The prion protein
      (PrP) gene sequence and the deduced amino acid alignment of prion protein in Tan
      sheep, a local Chinese sheep breed traditionally raised in Ningxia, northwestern
      China, were determined and variability of the PrP amino acids sequence was
      analyzed in this study. The PrP nucleic acids and amino acids sequences of 112
      Tan sheep were highly homogenous, although polymorphism of the PrP gene was
      detected at several sites, particularly codons 106, 154, and 171. The analysis of
      both sequences revealed that the most predominant allele at codons 136, 154 and
      171 in Tan sheep was ARQ, which was known to be associated with high
      susceptibility to scrapie in sheep. The result suggests that Tan sheep is
      potentially susceptible to scrapie. Our findings provide valuable information for
      future breeding projects to scrapie resistance in Tan sheep.

PMID- 21722720
TI  - Embryonic toxicity of sanguinarine through apoptotic processes in mouse
      blastocysts.
AB  - In this study, we examined the cytotoxic effects of sanguinarine, a phytoalexin
      with antimicrobial, anti-oxidant, anti-inflammatory and pro-apoptotic effects, on
      the blastocyst stage of mouse embryos, subsequent embryonic attachment and
      outgrowth in vitro and in vivo implantation via embryo transfer. Blastocysts
      treated with 0.5-2 MUM sanguinarine exhibited significantly increased apoptosis
      and a corresponding decrease in total cell number. Notably, the implantation
      success rates of blastocysts pretreated with sanguinarine were lower than that of
      their control counterparts. Moreover, in vitro treatment with 0.5-2 MUM
      sanguinarine was associated with increased resorption of post-implantation
      embryos and decreased fetal weight. Our results collectively indicate that
      sanguinarine induces apoptosis and retards early post-implantation development in
      vitro and in vivo. In addition, sanguinarine induces apoptotic injury effects on
      mouse blastocysts through intrinsic and extrinsic apoptotic signaling processes
      to impair sequent embryonic development. However, the extent to which
      sanguinarine exerts teratogenic effects on early human development is not known
      at present, and further studies are required to establish effective protection
      strategies against its cytotoxic effects.

PMID- 21722719
TI  - Sulfur mustard analog, 2-chloroethyl ethyl sulfide-induced skin injury involves
      DNA damage and induction of inflammatory mediators, in part via oxidative stress,
      in SKH-1 hairless mouse skin.
AB  - Bifunctional alkyalating agent, sulfur mustard (SM)-induced cutaneous injury is
      characterized by inflammation and delayed blistering. Our recent studies
      demonstrated that 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of
      SM that can be used in laboratory settings, induces oxidative stress. This could
      be the major cause of the activation of Akt/MAP kinase and AP1/NF-kappaB pathways
      that are linked to the inflammation and microvesication, and histopathological
      alterations in SKH-1 hairless mouse skin. To further establish a link between
      CEES-induced DNA damage and signaling pathways and inflammatory responses, skin
      samples from mice exposed to 2 mg or 4 mg CEES for 9-48 h were subjected to
      molecular analysis. Our results show a strong CEES-induced phosphorylation of
      H2A.X and an increase in cyclooxygenase-2 (COX-2), inducible NOS (iNOS), and
      matrix metalloproteinase-9 (MMP-9) levels, indicating the involvement of DNA
      damage and inflammation in CEES-induced skin injury in male and female mice.
      Since, our recent studies showed reduction in CEES-induced inflammatory responses
      by glutathione (GSH), we further assessed the role of oxidative stress in CEES
      related DNA damage and the induction of inflammatory molecules. Oral GSH (300
      mg/kg) administration 1h before CEES exposure attenuated the increase in both
      CEES-induced H2A.X phosphorylation (59%) as well as expression of COX-2 (68%),
      iNOS (53%) and MMP-9 (54%). Collectively, our results indicate that CEES-induced
      skin injury involves DNA damage and an induction of inflammatory mediators, at
      least in part via oxidative stress. This study could help in identifying
      countermeasures that alone or in combination, can target the unveiled pathways
      for reducing skin injury in humans by SM.

PMID- 21722721
TI  - Maternal exposure to fenarimol promotes reproductive performance in mouse
      offspring.
AB  - Although fenarimol is a widely used chlorinated fungicide applied to fruits and
      vegetables and is a suspected endocrine disrupter, transgenerational studies of
      low doses of fenarimol exposure are not currently available. The aims of this
      study are to address the effect of maternal exposure to low doses of fenarimol on
      the reproductive performance of offspring and to investigate the expression
      changes of genes associated with this effect. Pregnant mice were orally exposed
      to low doses (0, 2, 20, and 200 MUg/kg body weight) of fenarimol during
      gestational and lactational periods, and their offspring were assessed. The body
      and organ weights and anogenital distance (AGD) of mice offspring (F1) maternally
      exposed to fenarimol were determined, and the reproductive performances of these
      mice were assessed by mating and ovarian follicular and sperm analyses. Fenarimol
      exposed F1 mice had shortened AGDs, increased body weight with altered organ
      weights, increased number of pups, increased number of ovarian follicles, and
      enhanced sperm quality. Microarray data showed 82 upregulated and 743
      downregulated genes in the ovaries of fenarimol-exposed mice, in which Cyp17a1,
      Cyp19a1, and ERbeta were upregulated. In addition, Nobox, a pivotal gene required
      for proper folliculogenesis, was significantly increased in the ovaries of F1
      mice. In conclusion, maternal exposure to fenarimol promotes normal reproductive
      function in female mouse offspring by increasing the expression levels of genes
      crucial for ovarian folliculogenesis, identifying fenarimol as a chemical that
      stimulates reproductive performance. Thus, consumption of fenarimol-contaminated
      diets by mothers may possibly alter normal reproductive function of offspring in
      humans and wildlife.

PMID- 21722722
TI  - Targeted delivery of a poorly water-soluble compound to hair follicles using
      polymeric nanoparticle suspensions.
AB  - This study explored the utility of topically applied polymeric nanoparticle
      suspensions to target delivery of poorly water-soluble drugs to hair follicles.
      Several formulations of amorphous drug/polymer nanoparticles were prepared from
      ethyl cellulose and UK-157,147 (systematic name (3S,4R)-[6-(3
      hydroxyphenyl)sulfonyl]-2,2,3-trimethyl-4-(2-methyl-3-oxo-2,3-dihydropyridazin-6
      yloxy)-3-chromanol), a potassium channel opener, using sodium glycocholate (NaGC)
      as a surface stabilizer. Nanoparticle suspensions were evaluated to determine if
      targeted drug delivery to sebaceous glands and hair follicles could be achieved.
      In in vitro testing with rabbit ear tissue, delivery of UK-157,147 to the
      follicles was demonstrated with limited distribution to the surrounding dermis.
      Delivery to hair follicles was also demonstrated in vivo, based on stimulation of
      hair growth in tests of 100-nm nanoparticles with a C3H mouse model. The
      nanoparticles were well-tolerated, with no visible skin irritation. In vivo tests
      of smaller nanoparticles with a hamster ear model also indicated targeted
      delivery to sebaceous glands. The nanoparticles released drug rapidly in in vitro
      nonsink dissolution tests and were stable in suspension for 3 months. The present
      results show selective drug delivery to the follicle by follicular transport of
      nanoparticles and rapid release of a poorly water-soluble drug. Thus,
      nanoparticles represent a promising approach for targeted topical delivery of low
      solubility compounds to hair follicles.

PMID- 21722723
TI  - Ubiquitous plant compounds disturb cell-based assays.

PMID- 21722724
TI  - Coexistence of different base periodicities in prokaryotic genomes as related to
      DNA curvature, supercoiling, and transcription.
AB  - We analyzed the periodic patterns in E. coli promoters and compared the
      distributions of the corresponding patterns in promoters and in the complete
      genome to elucidate their function. Except the three-base periodicity, coincident
      with that in the coding regions and growing stronger in the region downstream
      from the transcriptions start (TS), all other salient periodicities are peaked
      upstream of TS. We found that helical periodicities with the lengths about B
      helix pitch ~10.2-10.5 bp and A-helix pitch ~10.8-11.1 bp coexist in the genomic
      sequences. We mapped the distributions of stretches with A-, B-, and Z-like DNA
      periodicities onto E. coli genome. All three periodicities tend to concentrate
      within non-coding regions when their intensity becomes stronger and prevail in
      the promoter sequences. The comparison with available experimental data indicates
      that promoters with the most pronounced periodicities may be related to the
      supercoiling-sensitive genes.

PMID- 21722725
TI  - Analysis of the genome and proteome composition of Bdellovibrio bacteriovorus:
      indication for recent prey-derived horizontal gene transfer.
AB  - The genome/proteome composition of Bdellovibrio bacteriovorus, the predatory
      microorganism that preys on other Gram-negative bacteria, has been analyzed. The
      study elucidates that translational selection plays a major role in genome
      compositional variation with higher intensity compared to other
      deltaproteobacteria. Other sources of variations having relatively minor
      contributions are local GC-bias, horizontal gene transfer and strand-specific
      mutational bias. The study identifies a group of AT-rich genes with distinct
      codon composition that is presumably acquired by Bdellovibrio recently from Gram
      negative prey-bacteria other than deltaproteobacteria. The proteome composition
      of this species is influenced by various physico-chemical factors, viz,
      alcoholicity, residue-charge, aromaticity and hydropathy. Cell-wall-surface
      anchor-family (CSAPs) and transporter proteins with distinct amino acid
      composition and specific secondary-structure also contribute notably to proteome
      compositional variation. CSAPs, which are low molecular-weight, outer-membrane
      proteins with highly disordered secondary-structure, have preference toward polar
      uncharged residues and cysteine that presumably help in prey-predator interaction
      by providing particular bonds of attachment.

PMID- 21722726
TI  - Effects of chronic mental stress and atherogenic diet on the immune inflammatory
      environment in mouse aorta.
AB  - Inflammation and stress are regarded as two important atherogenic factors.
      Because stress can affect leukocyte distribution, we hypothesized that stress
      mediated leukocyte extravasation can modify the inflammatory environment of the
      arterial wall possibly contributing to atherogenesis. To test this hypothesis we
      evaluated the inflammatory environment of the aorta in C57Bl/6 mice subjected to
      3 and 12 months of chronic stress and compared it to age matched non-stressed
      animals. Experiments were carried out in mice fed regular chow or atherogenic
      diets. Both treatments increased the expression of vascular and leukocyte
      adhesion molecules and leukocyte accumulation. At 3 months, stress but not an
      atherogenic diet elevated the number of CD4 cells, CD8 cells, macrophages,
      dendritic cells and neutrophils. These changes were associated with elevation of
      transcripts for ICAM-1 and VCAM-1, E-selectin and neuropeptide Y. At 12 months,
      stress or high cholesterol acted similarly to elevate the number of CD8 and
      macrophages, and synergistically on the number of all cell types investigated. At
      this time-point, strong synergism was also observed on the level of E-selectin
      and NPY in the aorta, but not in the circulation. Despite these effects,
      histological and morphological alterations of the arterial wall were severe in
      the atherogenic diet, but not in the stress groups. Thus, although stress and an
      atherogenic diet may both affect leukocyte accumulation in the aorta, they may
      contribute differently to atherogenesis.

PMID- 21722727
TI  - Neonatal exposure to bisphenol A or diethylstilbestrol alters the ovarian
      follicular dynamics in the lamb.
AB  - We hypothesized that neonatal xenoestrogen exposure affects the ovarian
      follicular dynamics in lambs. Female lambs were exposed from postnatal day (PND)
      1-14 to low doses of diethylstilbestrol (DES) or bisphenol A (BPA). At PND 30,
      the follicular dynamics and ovarian biomarkers (ERalpha, ERbeta, AR, Ki67, p27)
      were evaluated. Lambs exposed to DES or BPA showed a decline in the stock of
      primordial follicles with stimulation of follicular development. BPA reduced
      ovarian weight and increased the number of multioocyte follicles. BPA promoted
      proliferation of granulosa/theca cells in antral follicles, and increased both
      the number of antral atretic follicles and p27 expression. Neonatal exposure to
      BPA or DES reduced the primordial follicle pool by stimulating their initial
      recruitment and subsequent follicle development until antral stage. In
      prepubertal lambs, the accelerated folliculogenesis resulted in increased
      incidence of atretic follicles. These alterations may affect the ovarian function
      in the adult.

PMID- 21722729
TI  - Roles of platelets and macrophages in the protective effects of
      lipopolysaccharide against concanavalin A-induced murine hepatitis.
AB  - Platelets are reportedly causal in hepatitis. We previously showed that in mice,
      lipopolysaccharide (LPS) induces a reversible and macrophage-dependent hepatic
      platelet accumulation (HPA), including translocation of platelets into Disse
      spaces and their entry into hepatocytes. Concanavalin A (ConA), which induces
      hepatitis in mice via both T cells and macrophages, also induces HPA. Here, we
      examined the relationship between HPA and ConA-hepatitis. ConA-hepatitis and HPA
      were evaluated by serum transaminases, hepatic 5-hydroxytryptamine, and/or
      electron microscopy. Unlike LPS-induced HPA, ConA-induced HPA was only moderately
      dependent on phagocytic macrophages. Against expectations, platelet-depletion
      significantly exacerbated ConA-hepatitis, and anti-P-selectin antibody and P
      selectin receptor blockade reduced both ConA-induced HPA and hepatitis. Prior
      induction of HPA by pretreatment with low-dose LPS powerfully reduced ConA
      hepatitis. Such protection by LPS-pretreatment was not effective in mice depleted
      of phagocytic macrophages. In platelet-depleted mice, LPS-pretreatment severely
      exacerbated ConA-hepatitis. In mice depleted of both macrophages and platelets,
      neither ConA nor LPS-pretreatment+ConA induced hepatitis. In mice deficient in IL
      1alpha and IL-1beta (but not in TNFalpha), ConA-induced hepatitis was mild, and a
      protective effect of LPS was not detected. These results suggest that (i) there
      are causal and protective types of HPA, (ii) the causal type involves hepatic
      aggregation of platelets, which may be induced by platelet stimulants leaked from
      injured hepatocytes, (iii) the protective type is inducible by administration of
      prior low-dose LPS in a manner dependent on phagocytic (or F4/80-positive)
      macrophages, and (iv) IL-1 is involved in both the causal and protective types.

PMID- 21722730
TI  - FIDIA-Georgetown Institute for the Neurosciences: dreams, projects and actions
      with Erminio Costa.

PMID- 21722731
TI  - Preface. Fifty years of Neuropharmacology a tribute to Ermino Costa.

PMID- 21722732
TI  - Centrosomes, microtubules and neuronal development.
AB  - The formation of complex nervous systems requires processes that coordinate
      proliferation, migration and differentiation of neuronal cells. The remarkable
      morphological transformations of neurons as they migrate, extend axons and
      dendrites and establish synaptic connections, imply a strictly regulated process
      of structural organization and dynamic remodeling of the cytoskeleton. The
      centrosome serves as the main cytoskeleton-organizing center in the cell and is
      the classical site of microtubule nucleation and anchoring. Mutations in genes
      encoding centrosomal proteins cause severe neurodevelopmental disorders that lead
      to several neuropsychiatric diseases, such as lissencephaly, microcephaly and
      schizophrenia. While the centrosome has been considered crucial for coordinating
      neuronal migration and polarization, accumulating experimental findings seems to
      rule out a central role for the centrosome at later stages of neuronal
      development. Here, we will review these observations and discuss the importance
      of centrosomal and acentrosomal microtubule organization for neuronal
      development. This article is part of a Special Issue entitled 'Neuronal
      Function'.

PMID- 21722728
TI  - Oxidases and peroxidases in cardiovascular and lung disease: new concepts in
      reactive oxygen species signaling.
AB  - Reactive oxygen species (ROS) are involved in numerous physiological and
      pathophysiological responses. Increasing evidence implicates ROS as signaling
      molecules involved in the propagation of cellular pathways. The NADPH oxidase
      (Nox) family of enzymes is a major source of ROS in the cell and has been related
      to the progression of many diseases and even environmental toxicity. The
      complexity of this family's effects on cellular processes stems from the fact
      that there are seven members, each with unique tissue distribution, cellular
      localization, and expression. Nox proteins also differ in activation mechanisms
      and the major ROS detected as their product. To add to this complexity, mounting
      evidence suggests that other cellular oxidases or their products may be involved
      in Nox regulation. The overall redox and metabolic status of the cell,
      specifically the mitochondria, also has implications on ROS signaling. Signaling
      of such molecules as electrophilic fatty acids has an impact on many redox
      sensitive pathologies and thus, as anti-inflammatory molecules, contributes to
      the complexity of ROS regulation. This review is based on the proceedings of a
      recent international Oxidase Signaling Symposium at the University of
      Pittsburgh's Vascular Medicine Institute and Department of Pharmacology and
      Chemical Biology and encompasses further interaction and discussion among the
      presenters.

PMID- 21722733
TI  - Method for suppressing non-specific protein interactions observed with affinity
      resins.
AB  - Previous high throughput data analysis from several different approaches to
      affinity purification of protein complexes have revealed catalogues of
      contaminating proteins that persistently co-purify. Some of these contaminating
      proteins appear to be specific to one particular affinity matrix used or even to
      the artificial affinity tags introduced into endogenous proteins for the purpose
      of purification. A recent approach to minimising non-specific protein
      interactions in high throughput screens utilises pre-equilibration of affinity
      surfaces with thiocyanate anions to reduce non-specific binding of proteins. This
      approach not only reduces the effect of contaminating proteins but also promotes
      the enrichment of the specific binding partners. Here, we have taken this method
      and adapted it in an attempt to reduce the abundance of common contaminants in
      affinity purification experiments. We found the effect varied depending on the
      bait used, most likely due to its endogenous abundance.

PMID- 21722734
TI  - The composition of the carbon source and the time of cell harvest are critical
      determinants of the final yield of human papillomavirus type 16 L1 protein
      produced in Saccharomyces cerevisiae.
AB  - The L1 protein is a major component of prophylactic human papillomavirus (HPV)
      vaccines. Little effort has been made to improve the productivity of L1 protein
      by optimizing cell culture conditions although the high price of the vaccines is
      considered one of the factors limiting its widespread use. In biopharmaceutical
      manufacturing, strategies for optimizing culture conditions tend to focus on
      improvements in upstream processing rather than final yield because of the
      complexities of purification procedures. In this study, we investigated L1
      protein productivity as a function of the composition of the carbon source and
      the point of cell harvesting in the Saccharomyces cerevisiae expression system.
      We performed 44 series of purifications and achieved the highest productivity
      when the cells were cultured in a medium composed of 7% glucose and 1% galactose
      for 144 h. The final yield of L1 protein was markedly affected by the glucose:
      galactose ratio and the point at which cells were harvested: there was a 15-fold
      difference between the lowest and highest yields. We believe that optimization of
      the composition of the carbon source and the time of cell harvest have
      considerable potential for reducing the cost of production of HPV L1 protein.

PMID- 21722735
TI  - A PCR-directed cell-free approach to optimize protein expression using diverse
      fusion tags.
AB  - N-terminal fusion tags that enhance translation initiation or protein solubility
      are often used to facilitate protein overexpression. As the optimal tag for a
      given target protein cannot be predicted a priori, valuable time can be lost in
      cloning and manipulating the corresponding gene to generate different fusion
      constructs for expression analysis. We have developed a cell-free strategy that
      consolidates these steps, enabling the utility of a panel of nine fusion-tags to
      be determined within one to two days. This approach exploits the fact that PCR
      amplified DNA can be used as a template for cell-free protein synthesis.
      Overlap/extension PCR using the TEV protease site as the overlap region allows
      the fusion of different T7 promoter (T7p)-tag-TEV DNA fragments with a TEV-gene
      T7 terminator (T7ter) fragment. For tag sequences where the TEV site is not
      compatible, a short C3G3 repeat (CGr) sequence can be used as the overlap region.
      The resulting T7p-tag-TEV-gene-T7ter constructs are then used as templates for
      PCR-directed cell-free protein synthesis to identify which tag-TEV-gene fusion
      protein produces the highest amount of soluble protein. We have successfully
      applied this approach to the overexpression of the Adiponectin hypervariable
      domain (AHD). Five of the nine N-terminal fusion tags tested enabled the
      synthesis of soluble recombinant protein. The best of these was the Peptidyl
      prolylcis-trans isomerise B (PpiB) fusion tag which produces 1mg/ml amounts of
      soluble fusion protein. PpiB is an example of a new class of fusion tag known as
      the "stress-responsive proteins". Our results suggest that this cell-free fusion
      tag expression screen facilitates the rapid identification of suitable fusion
      tags that overcome issues such as poor expression and insolubility, often
      encountered using conventional approaches.

PMID- 21722736
TI  - Stability of gp41 hairpin and helix bundle assembly probed by combined stacking
      and circular dichroic approaches.
AB  - The envelope glycoprotein gp41 of HIV-1 undergoes structural rearrangement to
      form a helix hairpin during the virus-mediated fusion. Previous studies to
      investigate the folding and stability of hairpin did not monitor the end-to-end
      distance of the molecule. To directly probe the distance change, rhodamine dye
      was conjugated to the gp41 recombinant near the N- and C-terminal regions to
      detect the UV absorption and fluorescence intensity changes induced by the
      chemical denaturant guanidinium chloride (GdmCl). Using the singly- and doubly
      labeled constructs allowed us to distinguish between the hairpin formation and
      protein oligomerization. A biphasic transition of helical structure for the wild
      type protein was revealed by circular dichroism measurements while unfolding of
      the hairpin occurred at 6M GdmCl. The relevance of our study to the fusion
      inhibitor for HIV-1 was borne out by results on the mutants at the positions
      within the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR)
      regions. A monophasic transition at lower denaturant concentration was detected
      for the NHR mutant supporting the concept of differential stability of NHR and
      CHR helical structure. The conclusion that the observed unstacking of doubly
      labeled variant arises principally from the intra-molecular dimers was drawn from
      the unstacking of the protein labeled in the loop. Remarkably, it is deduced that
      the hairpin is more stable than the CHR helical structure. A model for
      denaturation of the helix hairpin bundle was proposed from these results. The
      biological implications of the findings and further applications of the distance
      based approach were discussed.

PMID- 21722737
TI  - Suppression subtractive hybridization coupled with microarray analysis to examine
      differential expression of genes in Japanese flounder Paralichthys olivaceus
      leucocytes during Edwardsiella tarda and viral hemorrhagic septicemia virus
      infection.
AB  - Transcriptional changes in the peripheral blood leucocytes (PBL) of Japanese
      flounder Paralichthys olivaceus challenged by Edwardsiella tarda and viral
      hemorrhagic septicemia virus (VHSV) were investigated using suppression
      subtractive hybridization (SSH) coupled with cDNA microarray analysis. First, we
      constructed an SSH cDNA library using mRNA samples isolated from PBL of P.
      olivaceus that had been experimentally infected with E. tarda. We then examined
      the transcriptional changes occurring in the PBL due to E. tarda and VHSV
      infection using a cDNA microarray produced using clones produced from the SSH
      library. A total of 565 and 180 cDNA sequences corresponding to mRNA species that
      are either up- or down-regulated by E. tarda infection were isolated by SSH.
      While host gene expression responses in response to E. tarda and VHSV infection
      share several response elements, distinct patterns of gene expression were also
      observed. Specifically, E. tarda infection enhanced the expression of cell
      adhesion molecules while VHSV enhanced the expression of interferon and
      proteasome-related genes. In challenge trials of the two infectious agents,
      expression profiles of chemokines were also observed to differ. The results
      indicated that distinguishing between viral and bacterial infection is possible
      based on the RNA expression profiles of PBL from infected fish.

PMID- 21722738
TI  - Optical brain monitoring for operator training and mental workload assessment.
AB  - An accurate measure of mental workload in human operators is a critical element
      of monitoring and adaptive aiding systems that are designed to improve the
      efficiency and safety of human-machine systems during critical tasks. Functional
      near infrared (fNIR) spectroscopy is a field-deployable non-invasive optical
      brain monitoring technology that provides a measure of cerebral hemodynamics
      within the prefrontal cortex in response to sensory, motor, or cognitive
      activation. In this paper, we provide evidence from two studies that fNIR can be
      used in ecologically valid environments to assess the: 1) mental workload of
      operators performing standardized (n-back) and complex cognitive tasks (air
      traffic control--ATC), and 2) development of expertise during practice of complex
      cognitive and visuomotor tasks (piloting unmanned air vehicles--UAV). Results
      indicate that fNIR measures are sensitive to mental task load and practice level,
      and provide evidence of the fNIR deployment in the field for its ability to
      monitor hemodynamic changes that are associated with relative cognitive workload
      changes of operators. The methods reported here provide guidance for the
      development of strategic requirements necessary for the design of complex human
      machine interface systems and assist with assessments of human operator
      performance criteria.

PMID- 21722739
TI  - The generation and validation of white matter connectivity importance maps.
AB  - Both the size and location of injury in the brain influences the type and
      severity of cognitive or sensorimotor dysfunction. However, even with advances in
      MR imaging and analysis, the correspondence between lesion location and clinical
      deficit remains poorly understood. Here, structural and diffusion images from 14
      healthy subjects are used to create spatially unbiased white matter connectivity
      importance maps that quantify the amount of disruption to the overall brain
      network that would be incurred if that region were compromised. Some regions in
      the white matter that were identified as highly important by such maps have been
      implicated in strategic infarct dementia and linked to various attention tasks in
      previous studies. Validation of the maps is performed by investigating the
      correlations of the importance maps' predicted cognitive deficits in a group of
      15 traumatic brain injury patients with their cognitive test scores measuring
      attention and memory. While no correlation was found between amount of white
      matter injury and cognitive test scores, significant correlations (r>0.68,
      p<0.006) were found when including location information contained in the
      importance maps. These tools could be used by physicians to improve surgical
      planning, diagnosis, and assessment of disease severity in a variety of
      pathologies like multiple sclerosis, trauma, and stroke.

PMID- 21722740
TI  - Basal functional connectivity within the anterior temporal network is associated
      with performance on declarative memory tasks.
AB  - Spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal,
      as measured by functional magnetic resonance imaging (fMRI) at rest, exhibit a
      temporally coherent activity thought to reflect functionally relevant networks.
      Antero-mesial temporal structures are the site of early pathological changes in
      Alzheimer's disease and have been shown to be critical for declarative memory.
      Our study aimed at exploring the functional impact of basal connectivity of an
      anterior temporal network (ATN) on declarative memory. A heterogeneous group of
      subjects with varying performance on tasks assessing memory was therefore
      selected, including healthy subjects and patients with isolated memory complaint,
      amnestic Mild Cognitive Impairment (aMCI) and mild Alzheimer's disease (AD).
      Using Independent Component Analysis on resting-state fMRI, we extracted a
      relevant anterior temporal network (ATN) composed of the perirhinal and
      entorhinal cortex, the hippocampal head, the amygdala and the lateral temporal
      cortex extending to the temporal pole. A default mode network and an executive
      control network were also selected to serve as control networks. We first
      compared basal functional connectivity of the ATN between patients and control
      subjects. Relative to controls, patients exhibited significantly increased
      functional connectivity in the ATN during rest. Specifically, voxel-based
      analysis revealed an increase within the inferior and superior temporal gyrus and
      the uncus. In the patient group, positive correlations between averaged
      connectivity values of ATN and performance on anterograde and retrograde object
      based memory tasks were observed, while no correlation was found with other
      evaluated cognitive measures. These correlations were specific to the ATN, as no
      correlation between performance on memory tasks and the other selected networks
      was found. Taken together, these findings provide evidence that basal
      connectivity inside the ATN network has a functional role in object-related,
      context-free memory. They also suggest that increased connectivity at rest within
      the ATN could reflect compensatory mechanisms that occur in response to early
      pathological insult.

PMID- 21722741
TI  - Cognition-induced modulation of serotonin in the orbitofrontal cortex: a
      controlled cross-over PET study of a delayed match-to-sample task using the 5
      HT2a receptor antagonist [18F]altanserin.
AB  - Behavioral and cellular studies indicate that serotonin interacting with the 5
      HT2a receptor (5-HT2aR) is involved in cognitive processes supporting working
      memory (WM). However, 5-HT receptor neuroimaging studies directly relating WM
      induced neuronal activations to concomitant changes in the availability of 5-HT
      receptors as a functional measure for serotonin release are lacking. This
      controlled cross-over PET study aimed to identify brain regions with WM-induced
      changes in the binding potential (BP(nd)) of the 5-HT2aR antagonist
      [(18)F]altanserin. Ten young males underwent a delayed match-to-sample task using
      photographs of faces and a control task. The BP(nd)s for both conditions were
      calculated by applying Ichise's noninvasive plot. Statistics were performed with
      the SPM toolbox statistical nonparametric mapping (SnPM3) particularly suited for
      analyzing whole-brain PET data in an exploratory way. A higher BP(nd) for
      [(18)F]altanserin during WM versus control was found in the orbitofrontal cortex
      (OFC) pointing towards an increased [(18)F]altanserin/5-HT2aR interaction in OFC
      while BP(nd) decreases during WM were not found. Furthermore, no BP(nd) changes
      in regions known from functional neuroimaging studies to be more specifically
      involved in WM were identified. These findings may suggest that the increased
      [(18)F]altanserin BP(nd) under WM challenge and hence the increased availability
      of 5-HT2aR reflects a decrease in local OFC serotonin. As the OFC plays a
      prominent role in decision-making and supports cognitive processes related to the
      central executive functions of WM it might be modulated by the serotoninergic
      system via the 5-HT2aR in order to support and optimize basic cognitive
      functions.

PMID- 21722742
TI  - Is left fronto-temporal connectivity essential for syntax? Effective
      connectivity, tractography and performance in left-hemisphere damaged patients.
AB  - Syntactic processing typically engages left inferior frontal gyrus and posterior
      middle temporal gyrus, and damage to these regions is associated with syntactic
      deficits. What has not been directly determined, however, is whether it is the
      effective connectivity between these regions - and therefore also the integrity
      of the white matter tracts that connect them - that underpins successful
      syntactic analysis. We addressed these related issues by obtaining measures of
      the psycho-physiological interaction between frontal and temporal regions and of
      the integrity of the major white matter tracts that directly connect them - the
      arcuate fasciculus and extreme capsule fibre system. We correlated these
      estimates with performance measures of syntax in a group of patients with left
      hemisphere damage and varying degrees of syntactic impairment. Good syntactic
      function was associated with enhanced effective connectivity and increased tract
      integrity, suggesting that intact connectivity between left frontal and temporal
      regions is essential for syntactic analysis rather than the activation of these
      regions per se.

PMID- 21722743
TI  - A densely sampled ITS phylogeny of the Cape flagship genus Erica L. suggests
      numerous shifts in floral macro-morphology.
AB  - Erica L. is the largest of the 'Cape' clades that together comprise around half
      of the disproportionately high species richness of the Cape Floristic Region
      (CFR) of South Africa. Around 840 species of Erica are currently recognised,
      C.680 of which are found in the CFR, the rest distributed across the rest of
      Southern Africa, the highlands of Tropical Africa and Madagascar, and Europe.
      Erica is taxonomically well documented, but very little is known about species
      level relationships. We present the first densely sampled phylogenetic analysis
      of Erica, using nuclear ribosomal DNA sequences (internal transcribed spacers;
      ITS) of c. 45% of the species from across the full geographic range of the genus,
      both Calluna and Daboecia (Ericeae; monotypic genera and putative sister groups
      of Erica), and further Ericoideae outgroups. Our results show both morphological
      and geographic coherence of some clades, but numerous shifts in floral macro
      morphology as represented by variation in individual morphological characters and
      pollination syndromes. European Ericeae is a paraphyletic grade subtending a
      monophyletic African/Malagasy Erica. Given the limited resolution of this single
      gene tree, more data are needed for further conclusions. Clades are identified
      that will serve as an effective guide for targeted sampling from multiple linkage
      groups.

PMID- 21722744
TI  - Molecular systematics and species limits in the Philippine fantails (Aves:
      Rhipidura).
AB  - Islands have long-attracted scientists because of their relatively simple biotas
      and stark geographic boundaries. However, for many islands and archipelagos, this
      simplicity may be overstated because of methodological and conceptual limitations
      when these biotas were described. One archipelago that has received relatively
      little recent attention is the Philippine islands. Although much of its biota was
      documented long ago, taxonomic revision and evolutionary study has been
      surprisingly scarce, and only a few molecular phylogenetic studies are beginning
      to appear. We present a molecular phylogeny and taxonomic revision for the
      Philippine fantails (Aves: Rhipidura) using nuclear and mitochondrial DNA
      sequences. Our results suggest that current taxonomy underestimates diversity in
      the group. Some morphologically distinct subspecies warrant species status,
      whereas one was indistinguishable genetically and morphologically and should not
      be retained. A few taxa require additional sampling for thorough taxonomic
      assessment. Patterns of diversity within Philippine Rhipidura mostly corroborate
      predictions of the Pleistocene aggregate island complex (PAIC) hypothesis, in
      which diversity is expected to be partitioned by deep water channels separating
      Pleistocene aggregate islands rather than by current islands. Substantial
      structure within PAIC clades indicates that additional drivers of diversification
      should be considered.

PMID- 21722745
TI  - Body mass index and alignment and their interaction as risk factors for
      progression of knees with radiographic signs of osteoarthritis.
AB  - OBJECTIVE: To investigate in which way body mass index (BMI) and alignment affect
      the risk for knee osteoarthritis (OA) progression. METHODS: Radiographs of 181
      knees from 155 patients (85% female, mean age 60 years) with radiographic signs
      of OA were analyzed at baseline and after 6 years. Progression was defined as 1
      point increase in joint space narrowing score in the medial or lateral
      tibiofemoral (TF) compartment or having knee prosthesis during the follow-up for
      knees with a Kellgren and Lawrence score >= 1 at baseline. BMI at baseline was
      classified as normal (<25 kg/m(2)), overweight (25-30) and obese (>30). Knee
      alignment on baseline radiographs was categorized as normal (TF angle between 182
      degrees  and 184 degrees ) and malalignment (<182 degrees  or >184 degrees ). We
      estimated the risk ratio (RR) with 95% confidence interval for knee OA
      progression for overweight and obese patients and for malaligned knees relative
      to normal using generalized estimating equations (GEE). Additionally, we
      estimated the added effect when BMI and malalignment were present together on
      progression of knee OA. Adjustments were made for age and sex. RESULTS: Seventy
      six knees (42%) showed progression: 27 in lateral and 66 in medial compartment.
      Knees from overweight and obese patients had an increased risk for progression
      (RR 2.4 (1.-3.6) and 2.9 (1.7-4.1), respectively). RRs of progression for
      malaligned, varus and valgus knee were 2.0 (1.3-2.8), 2.3 (1.4-3.1), and 1.7
      (0.97-2.6), respectively. When BMI and malalignment were included in one model,
      the effect of overweight, obesity and malalignment did not change. The added
      effect when overweight and malalignment were present was 17%. CONCLUSION:
      Overweight is associated with progression of knee OA and shows a small
      interaction with alignment. Losing weight might be helpful in preventing the
      progression of knee OA.

PMID- 21722746
TI  - Hygienic quality and antibiotic resistance profile of sliced butchery.
AB  - In order to investigate the microbiological quality of different meat products on
      the Greek market, 200 samples were collected from the following preparations:
      boiled turkey (n=50), boiled pork ham (n=50), smoked turkey (n=50) and smoked
      pork ham (n=50). In all cold meat preparations Clostridium perfringens vegetative
      and spore forms, Staphylococcus aureus, Escherichia coli and other Clostridium sp
      lec(-), as well as Lactobacillus, Bacillus sp. and Salmonella sp. were recovered.
      For instance Bacillus cereus was present in 6% of the samples. L. monocytogenes,
      Campylobacter jejuni and Campylobacter coli were rarely present (1-4%) while
      Yersinia enterocolitica and Campylobacter lari were absent. Differences in the
      occurrence of S. aureus, Salmonella sp., E. coli and spore forms of C.
      perfringens in boiled and smoked samples, reflects either the differences in the
      processing of the foods or could be associated to the extensive handling by the
      personnel during the purchasing (storage, slicing, wrapping). Antibiotic
      resistance on specific antibiotics for each pathogen was also studied. A
      multiresistance antibiotic profile was effective for most bacterial strains, and
      pronounced resistance profiles were observed for the commonly used antibiotics as
      ampicillin, penicillin, cephalothin, streptomycin followed by ceftriaxone and
      gentamycin. Albeit this high observed resistance profile, the tested strains
      generally conserved their susceptibility to amikacin, aztreonam, chloramphenicol
      and tylosin conserved an almost absent resistance. Antibiotics commonly used for
      therapeutic purposes, as well as antibiotics added to feed stuff of animals for
      increasing animal flesh production should contribute to the extensive spreading
      of antibiotic resistance in food and the environment. Systematically monitoring
      of the microbiological quality of cold butchery preparations must be done, in
      order to preserve food quality, optimizing the processing and elaboration methods
      of the product and safeguard the public health.

PMID- 21722747
TI  - Thermodynamic characterization of muscle tropomyosins from marine invertebrates.
AB  - Structural properties of invertebrate muscle tropomyosin (TM) have not been
      characterized in detail to date. TMs were thus purified from the mantle muscle of
      Japanese common squid Todarodes pacificus, the foot muscle of tokobushi abalone
      Haliotis diversicolor and the tail muscle of kuruma prawn Marsupenaeus japonicus,
      and investigated for their thermodynamic properties by circular dichroism (CD)
      spectrometry and differential scanning calorimetry (DSC). From the CD
      spectrometry data, the apparent melting temperature and the apparent free energy
      of unfolding at 20 degrees C were calculated to be 43.5 degrees C and 14.5 kJ/mol
      for the squid TM, 43.0 degrees C and 23.9 kJ/mol for the abalone TM, and 47.3
      degrees C and 50.2 kJ/mol for the prawn TM, respectively. From the DSC data, the
      total free energy of unfolding at 20 degrees C was calculated to be 129 kJ/mol,
      253 kJ/mol, and 271 kJ/mol for the squid, abalone, and prawn TMs, respectively.
      These results suggest that the thermal stability was in the order of prawn
      TM>abalone TM>squid TM.

PMID- 21722748
TI  - Smart medication through combination of synthetic biology and cell
      microencapsulation.
AB  - Recent advances in the field of synthetic biology have led to the design of a new
      generation of complex, man-made biological networks that operate inside living
      cells in a desired manner. Key elements of these systems are often controllable
      genetic switches that are capable of processing therapeutic signals by sensing
      and responding to the environment. For biomedical applications, however, it is
      necessary to seal these engineered cells in order to protect them from the host
      immune system and enable straightforward removal after completion of the therapy.
      A promising and successful approach is the microencapsulation of defined cells
      into a semi-permeable and biocompatible microcapsule. Shielding from the external
      environment still allows exchange to occur on a molecular basis. Thus, the
      powerful combination of synthetic biology and microencapsulation has been opening
      the door to novel and innovative cell-based biomedical applications, such as
      smart implantable drug delivery systems. This review highlights recent
      developments in the overlap of these two areas, thereby presenting promising
      developments and perspectives for future treatment strategies.

PMID- 21722749
TI  - Styrene biosynthesis from glucose by engineered E. coli.
AB  - Styrene is a large volume, commodity petrochemical with diverse commercial
      applications, including as a monomer building-block for the synthesis of many
      useful polymers. Here we demonstrate how, through the de novo design and
      development of a novel metabolic pathway, styrene can alternatively be
      synthesized from renewable substrates such as glucose. The conversion of
      endogenously synthesized l-phenylalanine to styrene was achieved by the co
      expression of phenylalanine ammonia lyase and trans-cinnamate decarboxylase.
      Candidate isoenzymes for each step were screened from bacterial, yeast, and plant
      genetic sources. Finally, over-expression of PAL2 from Arabidopsis thaliana and
      FDC1 from Saccharomyces cerevisiae (originally classified as ferulate
      decarboxylase) in an l-phenylalanine over-producing Escherichia coli host led to
      the accumulation of up to 260 mg/L in shake flask cultures. Achievable titers
      already approach the styrene toxicity threshold (determined as ~300 mg/L). To the
      best of our knowledge, this is the first report of microbial styrene production
      from sustainable feedstocks.

PMID- 21722750
TI  - The role of 20-HETE in androgen-mediated hypertension.
AB  - Androgen plays an important role in blood pressure regulation. Epidemiological
      studies have shown that men have a higher prevalence for developing hypertension
      than aged-matched, premenopausal women. Interestingly, postmenopausal women and
      women with polycystic ovary syndrome, both of which have increased endogenous
      androgen production, have elevated risks for hypertension suggesting that
      androgen may contribute to its development. Studies from our laboratory and
      others have provided substantial evidence that 20-hydroxyeicosatetraenoic acid
      (20-HETE) mediates the hypertension seen in rodents treated with androgen. 20
      HETE is the cytochrome P450 (CYP)-derived omega-hydroxylated metabolite of
      arachidonic acid. 20-HETE plays a complex role in blood pressure regulation. In
      the kidney tubules, 20-HETE decreases blood pressure by promoting natriuresis,
      while in the microvasculature it has a pressor effect. In the microcirculation,
      20-HETE participates in the regulation of vascular tone by sensitizing the smooth
      muscle cells to constrictor stimuli and contributes to myogenic, mitogenic and
      angiogenic responses. In addition, 20-HETE acts on the endothelium to promote
      endothelial dysfunction and endothelial activation. Recently, we have
      demonstrated that 20-HETE induces endothelial ACE thus setting forth a potential
      feed forward mechanism through activation of the renin-angiotensin-aldosterone
      system. In this review, we will discuss the pro-hypertensive effects of 20-HETE
      and its role in androgen-induced vascular dysfunction and hypertension.

PMID- 21722752
TI  - The roles of ER stress and P450 2E1 in CCl(4)-induced steatosis.
AB  - The role of ER stress on hepatic steatosis was investigated in a rat model. We
      injected CCl(4) into rats and found that CCl(4) could induce hepatic lipid
      accumulation, confirmed by Oil Red O staining and by measurement of triglyceride
      and cholesterol. The expression of ApoB, an apolipoprotein, was decreased in
      plasma and increased in the liver of CCl(4)-treated animals. The ER stress
      response was also significantly increased by CCl(4). P450 2E1 expression and
      activity were increased through interactions of P450 2E1 with NADPH-dependent
      P450 reductase (NPR) under CCl(4)-treated conditions. In HepG2 cells,
      intracellular lipid accumulation and its signaling were comparable to in vivo
      results. In order to elucidate the effect of the ER stress response itself,
      tunicamycin, an N-acetyl-glycosylation inhibitor, was injected into rats,
      followed by Oil Red O staining, lipid/triglyceride/cholesterol accumulation
      analysis, and examination of ApoB expression. Additionally, the ER stress
      response and upregulation of P450 2E1 were also confirmed in the tunicamycin
      treated rats. All of the responses were similar to those seen with CCl(4). The
      P450 2E1 inhibitor diallyl sulphide (DAS), N-acetylcysteine (NAC), and reduced
      glutathione (GSH) antioxidants also regulated processes, including ApoB
      expression and lipid accumulation in CCl(4)-treated animals. In the presence of
      tunicamycin, DAS or NAC/GSH regulated all of the pathological phenomena with the
      exception of the ER stress response. In summary, CCl(4) induces liver steatosis,
      a process involving ER stress-induced P450 2E1 activation and ROS production.

PMID- 21722751
TI  - Pleiotropic effects of prostaglandin E2 in hematopoiesis; prostaglandin E2 and
      other eicosanoids regulate hematopoietic stem and progenitor cell function.
AB  - Eicosanoids have been implicated in the physiological regulation of hematopoiesis
      with pleiotropic effects on hematopoietic stem cells and various classes of
      lineage restricted progenitor cells. Herein we review the effects of eicosanoids
      on hematopoiesis, focusing on new findings implicating prostaglandin E(2) in
      enhancing hematopoietic stem cell engraftment by enhancing stem cell homing,
      survival and self-renewal. We also describe a role for cannabinoids in
      hematopoiesis. Lastly, we discuss the yin and yang of various eicosanoids in
      modulating hematopoietic stem and progenitor cell functions and summarize
      potential strategies to take advantage of these effects for therapeutic benefit
      for hematopoietic stem cell transplantation.

PMID- 21722753
TI  - Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio).
AB  - Gankyrin is a small ankyrin-repeat protein that previous research has confirmed
      to be overexpressed in hepatocellular carcinoma (HCC). Although relevant
      literature has reported on gankyrin functions in cellular proliferation and
      tumorigenesis, the exact role of gankyrin is poorly understood in animal model
      systems. This study analyzed hepatic lipid accumulation in gankyrin transgenic
      (GK) zebrafish. Bromodeoxyuridine (BrdU)-positive cells were predominantly
      increased in the liver bud of GK larvae, indicating that gankyrin functionally
      promoted cell proliferation at the larval stage in GK fish. However, over 90% of
      the viable GK adults showed an increased lipid content, leading in turn to liver
      steatosis. Liver histology and oil red O staining also indicated the accumulation
      of fatty droplets in GK fish, consistent with the specific pathological features
      of severe steatosis. Molecular analysis revealed that gankyrin overexpression
      induced hepatic steatosis and modulated the expression profiles of four hepatic
      microRNAs, miR-16, miR-27b, miR-122, and miR-126, and 22 genes involved in lipid
      metabolism. Moreover, significantly increased hepatic cell apoptosis resulted in
      liver damage in GK adults, leading to liver failure and death after approximately
      10months. This study is the first to report gankyrin as a potential link between
      microRNAs and liver steatosis in zebrafish.

PMID- 21722754
TI  - Dengue virus replication in infected human keratinocytes leads to activation of
      antiviral innate immune responses.
AB  - Dengue virus (DENV) infection is the most prevalent mosquito-borne viral diseases
      in the world. Vector-mediated transmission of DENV is initiated when a blood
      feeding female Aedes mosquito injects saliva, together with the virus, into the
      skin of its mammalian host. Understanding the role of skin immune cells in the
      activation of innate immunity to DENV at the early times of infection is a
      critical issue that remains to be investigated. The purpose of our study was to
      assess the contribution of human keratinocytes as potential host cells to DENV in
      the activation of immune responses at the anatomical site of mosquito bite. We
      show that primary keratinocytes support DENV replication with the production of
      negative-stranded viral RNAs inside the infected cells. In the course of DENV
      life cycle, we observed the activation of host genes involved in the antiviral
      immune responses such as intracellular RNA virus sensors Toll-Like Receptor-3,
      Retinoic Acid Inducible Gene-I, Melanoma Differentiation Associated gene-5 and
      the RNA-dependent protein kinase R. DENV infection of primary keratinocytes also
      resulted in up-regulation of the expression of the antiviral Ribonuclease L gene,
      which subsequently led to enhanced production of IFN-beta and IFN-gamma.
      Depending on stages of viral replication, we observed the activation of host
      genes encoding the antimicrobial proteins beta-defensin and RNase 7 in infected
      keratinocytes. Our data demonstrate for the first time the permissiveness of
      human epidermal keratinocytes to DENV infection. Remarkably, DENV replication in
      keratinocytes contributes to the establishment of antiviral innate immunity that
      might occur in the early times after the bite of mosquito.

PMID- 21722755
TI  - Increased plasma levels of extracellular mitochondrial DNA during HIV infection:
      a new role for mitochondrial damage-associated molecular patterns during
      inflammation.
AB  - HIV infection is characterized by a chronic inflammatory state. Recently, it has
      been shown that mitochondrial DNA (mtDNA) released from damaged or dead cells can
      bind Toll like receptor-9 (TLR9), an intracellular receptor that responds to
      bacterial or viral DNA molecules. The activation of TLR9 present within monocytes
      or neutrophils results in a potent inflammatory reaction, with the production of
      proinflammatory cytokines. We measured plasma levels of mtDNA in different groups
      of HIV(+) patients, i.e., those experiencing an acute HIV infection (AHI), long
      term non progressors (LTNP), late presenters (LP) taking antiretroviral therapy
      for the first time, and healthy controls. We found that in AHI and LP mtDNA
      plasma levels were significantly higher than in healthy individuals or in LTNP.
      Plasma mtDNA levels were not correlated to peripheral blood CD4(+) T cell count,
      nor to markers of immune activation, but had a significant correlation with
      plasma viral load, revealing a possible role for mtDNA in inflammation, or as a
      biomarker of virus-induced damage.

PMID- 21722756
TI  - How to evaluate "spirometric" lung age--what method is approvable?
AB  - The method predicting lung age was originally proposed by Morris and Temple
      (1985). In their method, lung age was estimated by counting back the regression
      formula predicting normal value of FEV1. Since the normal value of FEV1 at a
      given age is not unique and exists within a certain range defined as 95%
      confidence interval, the backward value of lung age calculated with the original
      method includes statistical and physiological problems. Analyzing the problems
      related to the original method, we have developed a novel method with revising
      age-elicited variation in FEV1. When the original method is applied, the lung age
      of a person with measured FEV1 beyond upper-limit-of-normal (ULN) results in
      being remarkably young (sometimes, below zero), while that of a person with FEV1
      below lower-limit-of-normal (LLN) is estimated as being very elderly (sometimes,
      over 100). On the other hand, the novel method, in which age-related variation in
      FEV1 is reliably corrected, predicts a wide range of lung age even when measured
      FEV1 is significantly above ULN or below LLN.

PMID- 21722757
TI  - Vertebrate slow skeletal muscle actin - conservation, distribution and
      conformational flexibility.
AB  - The existence of a unique sarcomeric actin is demonstrated in teleosts that
      possess substantial amounts of slow skeletal muscle in the trunk. The slow
      skeletal isotype is conserved. There is one amino acid substitution between
      Atlantic herring slow skeletal actin and the equivalent in salmonids. Conversely,
      the intra-species variation is considerable; 13 substitutions between different
      herring skeletal isotypes (slow versus fast). The isomorphisms (non-conservative
      underlined: residues, 2, 3, 103, 155, 160, 165, 278, 281, 310, 329, 358, 360 and
      363) are restricted to sub-domains 1 and 3 and include the substitution Asp-360
      in 'slow' to Gln in 'fast' which results in an electrophoretic shift at alkaline
      pH. The musculature of the trunk facilitates the preparation of isoactins for
      biochemical study. Herring slow skeletal G-actin (Ca.ATP) is more susceptible to
      thermal, and urea, -induced denaturation and subtilisin cleavage than that in
      fast skeletal, but more stable than the counterpart in salmonids (one
      substitution, Gln354Ala) highlighting the critical nature of actin's carboxyl
      terminal insert. Fluorescent spectra of G-actin isoforms containing the
      isomorphism Ser155Ala in complexation with 2'-deoxy 3' O-(N'-Methylanthraniloyl)
      ATP infer similar polarity of the nucleotide binding cleft. An electrophoretic
      survey detected two skeletal actins in some (smelt and mackerel) but not all
      teleosts. One skeletal muscle actin was detected in frog and bird.

PMID- 21722758
TI  - 7 Mb de novo deletion within 8q21 in a patient with distal arthrogryposis type 2B
      (DA2B).
AB  - We report on a 7 11/12 years old male patient with normal mental development,
      club feet, ulnar deviation and mild camptodactyly as well as facial dysmorphism
      including high forehead, small mouth, broad nasal bridge, epicanthus, high
      palate, brachycephalus, short neck, and dysplastic ears consistent with distal
      arthrogryposis type 2B (DA2B). Mutational analysis of the genes MYH3, TNNI2,
      TNNT3 and TPM2, known to cause DA2B revealed no apparent disease causing
      mutation. Molecular karyotyping using a 250 K SNP array revealed a heterozygous
      de novo 7 Mb deletion of 8q21.11-8q21.13 containing 23 genes. Prioritisation of
      possible candidate genes using the bioinformatics tool ENDEAVOUR revealed three
      favoured genes, HEY1, FABP5 and FABP4 as potential causes of the phenotype. We
      propose that the 8q21 region contains a further locus which contributes to the
      genetically heterogeneous DA2B.

PMID- 21722759
TI  - Optimization of Brassica napus (canola) explant regeneration for genetic
      transformation.
AB  - Brassica napus (canola) is the second largest oilseed crop in the world. It is
      among the first crops to be genetically transformed, and genetically modified
      cultivars are in commercial production at very significant levels. Despite the
      early lead with respect to transgenesis, there remain cultivars that are
      recalcitrant to transformation. To address this, we have conducted an elaborate
      investigation of the conditions for regenerating shoots from hypocotyl explants
      from four genetic lines: Invigor 5020, Westar and Topas as well as a microspore
      culture derived line of Topas (Line 4079). We analyzed the effect of hormonal
      combinations in regeneration medium, donor plant age and explant type on the
      regeneration capacity of these plants. The analysis showed that hypocotyls of
      eight-day-old seedlings grown on media supplemented with 1mg/L
      dinitrophenylhydrazine (2,4-D) produced the most shoots. Globular somatic embryos
      emerged following two weeks of 2,4-D treatment. When transferred to the medium
      containing 5mg/L benzyladenine (BA), approximately 82% of embryos produced shoots
      within six weeks. Invigor plants were shown to regenerate more efficiently than
      Topas; the number of plantlets regenerated from Invigor was approximately 40-50%
      more as compared to Topas or Line 4079. When hypocotyl explants were co
      cultivated with the Agrobacterium strain GV3101 harboring a binary vector
      carrying a firefly luciferase reporter gene (LUC), significant numbers of
      plantlets were LUC-positive in a luciferase assay. Frequency of such plants were:
      Invigor 5020 (54.2 +/- 2.5%), Westar (53.7 +/- 5.3), Topas (16.0 +/- 0.24) and
      Line 4079 (13.4 +/- 4).

PMID- 21722760
TI  - Proteomic analysis of ontogenetic and diet-related changes in venom composition
      of juvenile and adult Dusky Pigmy rattlesnakes (Sistrurus miliarius barbouri).
AB  - Snake venom proteins show high levels of variation at the level of the individual
      yet the environmental and molecular mechanisms that generate this diversity
      remain unclear. Here we report the results of a controlled feeding experiment
      combined with proteomic analyses of periodically collected venom samples to
      assess the roles of ontogenetic and diet-related effects on venom composition of
      captive juvenile and adult Dusky Pigmy rattlesnakes (Sistrurus miliarius
      barbouri). Juvenile snakes fed from birth with mice, lizards, or frogs showed
      little evidence for an ontogenetic shift in venom composition from 5 to 26 months
      in terms of substantial changes in the relative abundance of major classes of
      venom toxins. However, there were fine-scale changes in the relative abundance of
      D49-PLA2 15, PI-SVMPs, and PIII-SVMP 28, and a decline in the abundance of other
      PIII-SVMPs. Although juveniles raised on different prey exhibited distinct
      relative toxin compositional change rates, at 26 months old, their venoms showed
      similar patterns of protein composition suggesting little effect of diet on the
      overall make-up of venom in snakes this age or younger. In contrast, adult
      females raised on different prey over a 26 month period showed prey-related
      changes in the relative abundance of major protein families from initial to final
      samples. Specifically, mouse-fed females showed substantial increases in the
      relative abundance of total PLA2s and serine proteinases of 95% and >100%,
      respectively, whereas comparable values for lizard- (42% and -22%) and frog-fed
      females (2% and 11%) were distinctly smaller in magnitude. Venom from adult
      snakes fed on different prey also showed distinct changes in the abundance of
      PLA2 molecules 15, 19a, and 19, which were, respectively, (>100%, 33%, 63%),
      (>100%, 0%, 35%), and (71%, 20%, -4%) for the mice-, lizard-, and frog-diet.
      Venom from snakes raised on frogs contained a small (1.1%) but consistent amount
      of a PLA2 molecule (15a) not present in snakes fed on mice or lizards. This work
      provides evidence that venom composition is somewhat plastic in both juvenile and
      adult S. m. barbouri and that, at least in adults, prey consumed may influence
      the relative abundance of possibly functionally-distinct classes of venom
      proteins.

PMID- 21722762
TI  - Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics.
AB  - Interleukin-2 (IL-2) is major cytokine involved in T cell proliferation,
      differentiation and apoptosis. Association between IL-2 and its receptor (IL-2R),
      triggers activation of complex signaling cascade governed by tyrosine
      phosphorylation that culminates in transcription of genes involved in modulation
      of the immune response. The complete characterization of the IL-2 pathway is
      essential to understand how aberrant IL-2 signaling results in several diseases
      such as cancer or autoimmunity and also how IL-2 treatments affect cancer
      patients. To gain insights into the downstream machinery activated by IL-2, we
      aimed to define the global tyrosine-phosphoproteome of IL-2 pathway in human T
      cell line Kit225 using high resolution mass spectrometry combined with
      phosphotyrosine immunoprecipitation and SILAC. The molecular snapshot at 5min of
      IL-2 stimulation resulted in identification of 172 proteins among which 79 were
      found with increased abundance in the tyrosine-phosphorylated complexes,
      including several previously not reported IL-2 downstream effectors.
      Combinatorial site-specific phosphoproteomic analysis resulted in identification
      of 99 phosphorylated sites mapping to the identified proteins with increased
      abundance in the tyrosine-phosphorylated complexes, of which 34 were not
      previously described. In addition, chemical inhibition of the identified IL-2
      mediated JAK, PI3K and MAPK signaling pathways, resulted in distinct alteration
      on the IL-2 dependent proliferation.

PMID- 21722761
TI  - Proteomic analysis of secretory products from the model gastrointestinal nematode
      Heligmosomoides polygyrus reveals dominance of venom allergen-like (VAL)
      proteins.
AB  - The intestinal helminth parasite, Heligmosomoides polygyrus bakeri offers a
      tractable experimental model for human hookworm infections such as Ancylostoma
      duodenale and veterinary parasites such as Haemonchus contortus. Parasite
      excretory-secretory (ES) products represent the major focus for immunological and
      biochemical analyses, and contain immunomodulatory molecules responsible for
      nematode immune evasion. In a proteomic analysis of adult H. polygyrus secretions
      (termed HES) matched to an extensive transcriptomic dataset, we identified 374
      HES proteins by LC-MS/MS, which were distinct from those in somatic extract HEx,
      comprising 446 identified proteins, confirming selective export of ES proteins.
      The predominant secreted protein families were proteases (astacins and other
      metalloproteases, aspartic, cysteine and serine-type proteases), lysozymes,
      apyrases and acetylcholinesterases. The most abundant products were members of
      the highly divergent venom allergen-like (VAL) family, related to Ancylostoma
      secreted protein (ASP); 25 homologues were identified, with VAL-1 and -2 also
      shown to be associated with the parasite surface. The dominance of VAL proteins
      is similar to profiles reported for Ancylostoma and Haemonchus ES products.
      Overall, this study shows that the secretions of H. polygyrus closely parallel
      those of clinically important GI nematodes, confirming the value of this parasite
      as a model of helminth infection.

PMID- 21722763
TI  - Choreographing pluripotency and cell fate with transcription factors.
AB  - The cellular identity of both pluripotent and differentiated cells is defined by
      the concerted interplay of transcriptional factors as well as other modulators
      such as epigenetic and signaling mediators. Therefore, the manipulation of a
      cell's transcriptional network directly facilitates inter-conversion between
      cellular identities. Understanding the molecular regulation of cell fate changes,
      including those involved in pluripotency, is crucial in realizing the practical
      potential of pluripotent and induced cell types. Here we review the advancements
      in the role of transcription factors in pluripotency, as well as in the
      conversion between and within pluripotent and somatic cell types.

PMID- 21722764
TI  - Corticosterone selectively targets endo-cortical surfaces by an osteoblast
      dependent mechanism.
AB  - BACKGROUND: The pathogenesis of glucocorticoid-induced osteoporosis remains ill
      defined. In this study, we examined the role of the osteoblast in mediating the
      effects of exogenous glucocorticoids on cortical and trabecular bone, employing
      the Col2.3-11betaHSD2 transgenic mouse model of osteoblast-targeted disruption of
      glucocorticoid signalling. METHODS: Eight week-old male transgenic (tg) and wild
      type (WT) mice (n=20-23/group) were treated with either 1.5 mg corticosterone
      (CS) or placebo for 4 weeks. Serum tartrate-resistant acid phosphatase 5b
      (TRAP5b) and osteocalcin (OCN) were measured throughout the study. Tibiae and
      lumbar vertebrae were analysed by micro-CT and histomorphometry at endpoint.
      RESULTS: CS suppressed serum OCN levels in WT and tg mice, although they remained
      higher in tg animals at all time points (p<0.05). Serum TRAP5b levels increased
      in WT mice only. The effect of CS on cortical bone differed by site: At the
      endosteal surface, exposure to CS significantly increased bone resorption and
      reduced bone formation, resulting in a larger bone marrow cavity cross-sectional
      area (p<0.01). In contrast, at the pericortical surface bone resorption was
      significantly decreased accompanied with a significant increase in pericortical
      cross-sectional area (p<0.05) while bone formation remained unaffected. Vertebral
      cortical thickness and area were reduced in CS treatment mice. Tg mice were
      partially protected from the effects of exogenous CS, both on a cellular and
      structural level. At the CS doses used in this study, trabecular bone remained
      largely unaffected. CONCLUSION: Endocortical osteoblasts appear to be
      particularly sensitive to the detrimental actions of exogenous glucocorticoids.
      The increase in tibial pericortical cross-sectional area and the according
      changes in pericortical circumference suggest an anabolic bone response to GC
      treatment at this site. The protection of tg mice from these effects indicates
      that both catabolic and anabolic action of glucocorticoids are, at least in part,
      mediated by osteoblasts.

PMID- 21722765
TI  - Influencing safe perioperative practice through quality improvement.

PMID- 21722766
TI  - Sharps safety in the operating room.

PMID- 21722767
TI  - Trending toward paperless.

PMID- 21722768
TI  - Using nurse-to-patient telephone calls to reduce day-of-surgery cancellations.
AB  - Day-of-surgery cancellations are costly and frustrating for both the patient and
      the health care team. This is especially true in ambulatory surgical centers
      where it can be difficult to schedule a replacement procedure on short notice.
      Preoperative nurses at the University of North Carolina Health Care ambulatory
      surgical center were able to decrease the daily cancellation rate by 53%,
      increase patient satisfaction scores, and increase OR use by targeting three main
      reasons for cancellations during a preoperative telephone call. A nurse calls
      each patient three business days before the scheduled surgery and uses a script
      to communicate important preoperative information and to address any questions or
      concerns. The nurse then reports any new information or concerns he or she has
      learned from the telephone call to the scheduling clinic, anesthesia team, or the
      surgeon. These calls have resulted in major decreases in cancellations related to
      no shows, NPO requirements, and lack of a responsible adult present to drive the
      patient home.

PMID- 21722769
TI  - Factors associated with multidrug-resistant Acinetobacter transmission: an
      integrative review of the literature.
AB  - Multidrug-resistant (MDR) Acinetobacter infections are occurring at alarming
      rates in traumatic war injuries. Causative factors have not been specifically
      identified. We used an integrative review of the literature guided by the
      Identifying, Organizing, and Synthesizing strategy to identify factors related to
      MDR Acinetobacter transmission. We identified five major themes of commonality
      relating to transmission-wound types, risk factors, contributing factors, modes
      of transmission, and prevention strategies-and we identified studies that should
      be replicated in military populations. We identified sources of transmission (ie,
      environment to wound, health care worker to wound) and interventions to reduce or
      eliminate health care-associated or surgical site MDR Acinetobacter infections
      (ie, using strict infection control guidelines, appropriate use of antibiotics,
      notification of infected patients).

PMID- 21722770
TI  - Safe positioning for robotic-assisted laparoscopic prostatectomy.
AB  - Robotic-assisted laparoscopic prostatectomy is a surgical procedure performed to
      eradicate prostate cancer. Use of robotic assistance technology allows smaller
      incisions than the traditional laparoscopic approach and results in better
      patient outcomes, such as less blood loss, less pain, shorter hospital stays, and
      better postoperative potency and continence rates. This surgical approach creates
      unique challenges in patient positioning for the perioperative team because the
      patient is placed in the lithotomy with steep Trendelenburg position. Incorrect
      positioning can lead to nerve damage, pressure ulcers, and other complications.
      Using a special beanbag positioning device made specifically for use with this
      severe position helps prevent these complications.

PMID- 21722771
TI  - AORN Ergonomic Tool 5: Tissue Retraction in the Perioperative Setting.
AB  - Manual retraction, a task performed to expose the surgical site, poses a high
      risk for musculoskeletal disorders that affect the hands, arms, shoulders, neck,
      and back. In recent years, minimally invasive and laparoscopic procedures have
      led to the development of multifunctional instruments and retractors capable of
      performing these functions that, in many cases, has eliminated the need for
      manual retraction. During surgical procedures that are not performed
      endoscopically, the use of self-retaining retractors enables the assistant to
      handle tissue and use exposure techniques that do not require prolonged manual
      retraction. Ergonomic Tool #5: Tissue Retraction in the Perioperative Setting
      provides an algorithm for perioperative care providers to determine when and
      under what circumstances manual retraction of tissue is safe and when the use of
      a self-retaining retractor should be considered.

PMID- 21722772
TI  - Peripheral nerve blocks in the outpatient surgery setting.
AB  - Peripheral nerve blocks involve injecting local anesthesia near or around a nerve
      or nerve plexus. This form of anesthesia allows surgeons to perform more complex
      surgeries and provides extended postoperative analgesia for patients. Patients
      experience reduced postoperative pain and length of hospital stay and increased
      satisfaction with the outcome of surgery because they are less likely to
      experience adverse effects. Use of peripheral nerve blocks in an outpatient
      setting is becoming more common and has increased the perioperative nurse's
      patient care responsibilities. The nurse must perform a preblock assessment and
      assist the anesthesia professional with administration of the block. Major
      responsibilities of the nurse include identifying and managing potential adverse
      effects (eg, pneumothorax, toxicity) associated with block administration and
      patient discharge education.

PMID- 21722773
TI  - Education and experience make a difference: results of a predictor study.
AB  - Growing evidence demonstrates the link between the quality of care nurses
      provide, patient outcomes, and nurses' level of qualification and expertise.
      Little attention has been given to measuring the influence of experience and
      education on nurses' perceptions of their perioperative competence. To describe
      the influence of years of OR experience and specialty education on nurses'
      perioperative competence, we surveyed 345 perioperative nurses from two
      Australian hospitals. We developed the 98-item survey to specifically measure
      perioperative competence across eight domains that reflect knowledge, skills, and
      attitudes. We used multiple regression to analyze the data. There were
      differences in nurses' perceived perioperative competence based on perioperative
      experience and education, with more experienced nurses and those with specialty
      education reporting higher competence scores. Multiple regression analysis showed
      that experience and specialty education contributed to 23.3% of the variance in
      nurses' perception of their perioperative competence. Education initiatives are
      commonly used to address knowledge and attitudinal deficits; however, the results
      of this study suggest that education may only partly address these shortfalls.
      Hospital education programs should include staff development strategies
      associated with succession planning. Strategies that build on perioperative
      nurses' clinical experience and expertise will provide them with opportunites to
      develop skills in coordination and clinical leadership. Importantly, education
      occurs in a context and thus is embedded in clinical practice.

PMID- 21722774
TI  - Key strategies for eliminating sharps injuries during surgery.

PMID- 21722777
TI  - Collegiality vs. competence.

PMID- 21722780
TI  - Introduction.

PMID- 21722781
TI  - Comprehensive medical management of peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is highly prevalent and is associated with high
      morbidity and mortality. The medical management of PAD involves a comprehensive
      approach to the patient with emphasis on cardiovascular risk factor modification
      in addition to therapies directed at treatment of limb symptoms. This manuscript
      will review the current status of medical therapy in management of patients with
      PAD.

PMID- 21722782
TI  - Carotid stenting or carotid surgery in average surgical-risk patients:
      interpreting the conflicting clinical trial data.
AB  - There are generic as well as carotid-specific trial design considerations that
      have the potential to materially affect the outcomes and interpretation of
      comparative studies between carotid artery stenting and carotid endarterectomy.
      Recently, a series of trials in patients who are at average risk for carotid
      surgery have been reported. The European trials have all suffered from allowing
      an imbalance in operator experience between stenting and surgery and have
      consistently allowed stenting procedures without embolic protection. The
      combination of inexperienced operators and lack of embolic protection may be
      responsible for their negative stenting results. The Carotid Revascularization
      with Endarterectomy vs. Stenting Trial avoided both of these problems, having a
      threshold of experience for operators as well as mandating embolic protection be
      used. The Carotid Revascularization with Endarterectomy vs. Stenting Trial
      demonstrated noninferiority for stenting compared with surgery in average-risk
      symptomatic and asymptomatic patients, leading to Food and Drug Administration
      approval of a stent and protection for this indication. This has been recently
      followed by guidelines supporting the role of stenting compared with surgery from
      a broad range of professional societies.

PMID- 21722783
TI  - Treatment strategies for carotid stenosis in patients at increased risk for
      surgery.
AB  - The purpose of carotid revascularization is stroke prevention. The merits of
      carotid revascularization as well as the type of revascularization are dependent
      on the "natural risk" and the "revascularization risk." In general, the natural
      risk of stroke in any patient with carotid stenosis (CS) is dependent on the
      symptomatic status of the patient and CS severity. Contemporary choices for
      carotid revascularization include carotid endarterectomy (CEA) and carotid artery
      stenting (CAS). Anatomical (hostile neck situations, severe bilateral CS, CEA
      restenosis) and clinical (severe cardiopulmonary diseases, prior cranial nerve
      injury) factors may increase the risk of CEA. Likewise, anatomical (complex
      aortic arch and brachiocephalic arterial anatomy, presence of thrombus, and heavy
      calcification) and clinical (need for heart surgery within 30 days) factors may
      increase the risk of CAS. Other factors such as the presence of symptomatic CS
      (transient ischemic attack or stroke within 6 months), decreased cerebral
      reserve, chronic kidney disease, and age older than 75 years may increase the
      risk of CEA and CAS. In general, symptomatic patients with severe CS exceed
      revascularization risk. In contrast, asymptomatic patients who are high risk for
      CEA should be considered for CAS because the natural risk of stroke should
      undergo careful assessment of baseline cognitive function, aortic arch and
      carotid artery anatomy, and likelihood of survival for 3 years. Patients who have
      normal cognitive function, favorable anatomy, and high likelihood of survival
      more than 3 years should be considered for CAS, whereas patients with multiple
      unfavorable features may be treated with optimal medical therapy, without
      revascularization.

PMID- 21722784
TI  - Renal artery stenosis: optimizing diagnosis and treatment.
AB  - Renal artery stenosis (RAS) is the most commonly caused by atherosclerosis, with
      fibromuscular dysplasia being the most frequent among other less common
      etiologies. A high index of suspicion based on clinical features is essential for
      diagnosis. Revascularization strategies are currently a topic of discussion and
      debate. When revascularization is deemed appropriate, atherosclerotic RAS is most
      often treated with stent placement, whereas patients with fibromuscular dysplasia
      are usually treated with balloon angioplasty. Ongoing randomized trials should
      help to better define the optimal management of RAS.

PMID- 21722785
TI  - Chronic mesenteric ischemia: diagnosis and management.
AB  - Chronic mesenteric ischemia (CMI) is the most common vascular disorder involving
      the intestines, however it is unusual in clinical practice. The redundancy of the
      visceral circulation with multiple interconnections between the superior
      mesenteric artery (SMA) and the inferior mesenteric artery (IMA) is the most
      likely explanation for the infrequent occurrence of CMI in clinical practice.
      Atherosclerosis is by the far the most common etiology of CMI. The increased
      utilization of diagnostic abdominal cross-sectional imaging has increased the
      recognition of atherosclerotic mesenteric stenoses. CMI is a clinical diagnosis,
      based upon symptoms and consistent anatomic findings. The classic setting for CMI
      is a female patient presenting with post-prandial abdominal discomfort that
      results in significant weight loss. Endovascular therapy with stenting has become
      the most common method chosen for revascularization having replaced open surgery
      with its associated morbidity and mortality.

PMID- 21722786
TI  - Claudication: treatment options for femoropopliteal disease.
AB  - Intermittent claudication due to chronic femoropopliteal obstruction is a common
      disease, and patients are potentially severely disabled by the painful limitation
      of walking capacity. Despite major advances in pharmacological therapy of
      atherosclerosis, effective medication specifically for treatment of intermittent
      claudication is still not available. Training programs work well for patients
      with mild to moderate symptoms but frequently fail in patients with very
      compromised walking capacity. Patients with severe symptoms and markedly reduced
      quality of life therefore are candidates for revascularization. The preferred
      method of revascularization is endovascular treatment; this includes simple
      balloon angioplasty, debulking techniques, stent implantation, and, more
      recently, drug eluting technologies. Selected patients are candidates for surgery
      which encompasses endarterectomy of focal common femoral lesions as well as
      femoropopliteal bypass surgery in patients with very extensive disease or after
      failed endovascular approaches. The following article reviews current aspects of
      the management of femoropopliteal disease in patients with intermittent
      claudication.

PMID- 21722787
TI  - Critical limb ischemia: endovascular strategies for limb salvage.
AB  - Critical limb ischemia (CLI) represents the most severe clinical manifestation of
      peripheral arterial disease, defined as the presence of chronic ischemic rest
      pain, ulcers, or gangrene attributable to objectively proven arterial occlusive
      disease. The dominant pathology underlying CLI is atherosclerosis, distributed at
      multiple levels along the length of the lower extremity and with a propensity for
      involvement of the tibial vessels in the leg and the small vessels of the foot.
      To achieve limb salvage in patients with CLI, revascularization of the affected
      limb is generally required. In contemporary practice, endovascular techniques are
      rapidly replacing surgical bypass as the first option for revascularization for
      CLI based on high technical success rates and low rates of procedure-related
      morbidity and mortality. This review will describe the clinical strategy of the
      authors who have adopted an endovascular-first approach to revascularization in
      treating patients with CLI and summarize the clinical outcomes of endovascular
      therapy in this population.

PMID- 21722788
TI  - Venous ablation therapy: indications and outcomes.
AB  - Venous disease has long been recognized as a progressive, debilitating, and
      recurrent problem. Until recently, venous insufficiency was often undertreated
      due to a lack of therapeutic modalities. During the past decade, an explosion in
      the treatment options has occurred. Endovenous ablation therapy has nearly
      replaced the conventional surgical treatments for patients with superficial
      venous insufficiency. Dramatic changes in therapy are also available for deep
      venous thrombosis but are not the subject of this review. These newer techniques
      are much less invasive and consequently have reduced risks of wound complications
      or bleeding. In addition, they can be performed easily in the office setting with
      local anesthesia. Higher-risk patients can now be considered for these less
      invasive treatments to reduce their ambulatory venous hypertension. With the
      lower procedural risks and the dramatically shortened recovery times, earlier
      intervention can be entertained. This helps prevent the development of venous
      stasis ulceration and other sequelae of progressive venous insufficiency.

PMID- 21722789
TI  - Endovascular therapies to treat iliofemoral deep venous thrombosis.
AB  - Lower extremity deep venous thrombosis (DVT) has traditionally been divided into
      proximal and distal DVT. Proximal DVT is further subdivided into iliofemoral DVT,
      involving the common femoral vein and/or iliac vein, and represents an
      obstructive disease process with a worse prognosis than proximal DVT without
      involvement of these large draining veins. The anatomical reasons will be
      explored, and the data supporting these findings will be examined. Because
      iliofemoral DVT portends a worse prognosis in patients with lower extremity DVT,
      the risk-benefit profile is altered compared with proximal DVT without
      involvement of the common femoral or iliac draining veins. The initial
      anticoagulation management and catheter-based, invasive therapies currently
      available for treatment of iliofemoral DVT will be described, and the data
      supporting these techniques will be examined.

PMID- 21722790
TI  - Novel bacterial MerR-like regulators their role in the response to carbonyl and
      nitrosative stress.
AB  - Recognition of the diversity of transcriptional regulators of the MerR family has
      increased considerably over the last decade and it has been established that not
      all MerR-like regulators are involved in metal ion recognition. A new type of
      MerR-like regulator was identified in Neisseria gonorrhoeae that is distinct from
      metal-binding MerR proteins. This novel transcription factor, the Neisseria merR
      like regulator (NmlR) is related to a large and diverse group of MerR-like
      regulators. A common feature of the majority of the genes encoding the nmlR
      related genes is that they predicted to control the expression of adhC, which
      encodes a glutathione-dependent alcohol dehydrogenase. The function of the NmlR
      regulon appears to be to defend the bacterial cell against carbonyl stress and in
      some cases nitrosative stress. A potential role for NmlR in bacterial
      pathogenesis has been identified in Neisseria gonorrhoeae and Streptococcus
      pneumoniae. Although it is not known how NmlR is activated it is suggested that
      conserved cysteine residues may be involved in thiol-based signaling.

PMID- 21722791
TI  - Quorum sensing: regulating the regulators.
AB  - Many bacteria use 'quorum sensing' (QS) as a mechanism to regulate gene induction
      in a population-dependent manner. In its simplest sense this involves the
      accumulation of a signaling metabolite during growth; the binding of this
      metabolite to a regulator or multiple regulators activates induction or
      repression of gene expression. However QS regulation is seldom this simple,
      because other inputs are usually involved. In this review we have focussed on how
      those other inputs influence QS regulation and as implied by the title, this
      often occurs by environmental or physiological effects regulating the expression
      or activity of the QS regulators. The rationale of this review is to briefly
      introduce the main QS signals used in Gram-negative bacteria and then introduce
      one of the earliest understood mechanisms of regulation of the regulator, namely
      the plant-mediated control of expression of the TraR QS regulator in
      Agrobacterium tumefaciens. We then describe how in several species, multiple QS
      regulatory systems can act as integrated hierarchical regulatory networks and
      usually this involves the regulation of QS regulators. Such networks can be
      influenced by many different physiological and environmental inputs and we
      describe diverse examples of these. In the final section, we describe different
      examples of how eukaryotes can influence QS regulation in Gram-negative bacteria.

PMID- 21722792
TI  - The single-domain globin of Vitreoscilla: augmentation of aerobic metabolism for
      biotechnological applications.
AB  - Extensive studies have revealed that large-scale, high-cell density bioreactor
      cultivations have significant impact on metabolic networks of oxygen-requiring
      production organisms. Oxygen transfer problems associated with fluid dynamics and
      inefficient mixing efficiencies result in oxygen gradients, which lead to reduced
      performance of the bioprocess, decreased product yields, and increased production
      costs. These problems can be partially alleviated by improving bioreactor
      configuration and setting, but significant improvements have been achieved by
      metabolic engineering methods, especially by heterologously expressing
      Vitreoscilla hemoglobin (VHb). Vast numbers of studies have been accumulating
      during the past 20 years showing the applicability of VHb to improve growth and
      product yields in a variety of industrially significant prokaryotic and
      eukaryotic hosts. The global view on the metabolism of globin-expressing
      Escherichia coli cells depicts increased energy generation, higher oxygen uptake
      rates, and a decrease in fermentative by-product excretion. Transcriptome and
      metabolic flux analysis clearly demonstrate the multidimensional influence of
      heterologous VHb on the expression of stationary phase-specific genes and on the
      regulation of cellular metabolic networks. The exact biochemical mechanisms by
      which VHb is able to improve the oxygen-limited growth remain poorly understood.
      The suggested mechanisms propose either the delivery of oxygen to the respiratory
      chain or the detoxification of reactive nitrogen species for the protection of
      cytochrome activity. The expression of VHb in E. coli bioreactor cultures is
      likely to assist bacterial growth through providing an increase in available
      intracellular oxygen, although to fully understand the exact role of VHb in vivo,
      further analysis will be required.

PMID- 21722793
TI  - Singlet oxygen stress in microorganisms.
AB  - Singlet oxygen is the primary agent of photooxidative stress in microorganisms.
      In photosynthetic microorganisms, sensitized generation by pigments of the
      photosystems is the main source of singlet oxygen and, in nonphotosynthetic
      microorganisms, cellular cofactors such as flavins, rhodopsins, quinones, and
      porphyrins serve as photosensitizer. Singlet oxygen rapidly reacts with a wide
      range of cellular macromolecules including proteins, lipids, DNA, and RNA, and
      thereby further reactive substances including organic peroxides and sulfoxides
      are formed. Microorganisms that face high light intensities or exhibit potent
      photosensitizers have evolved specific mechanisms to prevent photooxidative
      stress. These mechanisms include the use of quenchers, such as carotenoids, which
      interact either with excited photosensitizer molecules or singlet oxygen itself
      to prevent damage of cellular molecules. Scavengers like glutathione react with
      singlet oxygen. Despite those protection mechanisms, damage by reactions with
      singlet oxygen on cellular macromolecules disturbs cellular functions.
      Microorganisms that regularly face photooxidative stress have evolved specific
      systems to sense singlet oxygen and tightly control the removal of singlet oxygen
      reaction products. Responses to photooxidative stress have been investigated in a
      range of photosynthetic and nonphotosynthetic microorganisms. However, detailed
      knowledge on the regulation of this response has only been obtained for the
      phototrophic alpha-proteobacterium Rhodobacter sphaeroides. In this organism and
      in related proteobacteria, the extracytoplasmic function (ECF) sigma factor RpoE
      is released from the cognate antisigma factor ChrR in the presence of singlet
      oxygen and triggers the expression of genes providing protection against
      photooxidative stress. Recent experiments show that singlet oxygen acts as a
      signal, which is sensed by yet unknown components and leads to proteolysis of
      ChrR. RpoE induces expression of a second alternative sigma factor, RpoH(II),
      which controls a large set of genes that partially overlaps with the heat-shock
      response controlled by RpoH(I). In addition to the transcriptional control of
      gene regulation by alternative sigma factors, a set of noncoding small RNAs
      (sRNAs) appear to affect the synthesis of several proteins involved in the
      response to photooxidative stress. The interaction of mRNA targets with those
      sRNAs is usually mediated by the RNA chaperone Hfq. Deletion of the gene encoding
      Hfq leads to a singlet oxygen-sensitive phenotype, which underlines the control
      of gene regulation on the posttranscriptional level by sRNAs in R. sphaeroides.
      Hence, a complex network of different regulatory components controls the defense
      against photooxidative stress in anoxygenic photosynthetic bacteria.

PMID- 21722794
TI  - Metal sensing in Salmonella: implications for pathogenesis.
AB  - Both the essentiality and toxicity of transition metals are exploited as part of
      mammalian immune defenses against bacterial infection. Salmonella serovars
      continue to cause serious medical and veterinary problems worldwide and detecting
      deficiency and excess of different metal ions (such as copper, iron, zinc,
      manganese, nickel, and cobalt) is fundamental to their virulence. This involves
      multiple DNA-binding metal-responsive transcription factors that discriminate
      between elements and trigger expression of genes that mediate appropriate
      responses to metal fluxes. This review focuses on the metal stresses encountered
      by Salmonella during infection and the roles of the different metal-sensing
      regulatory proteins and their target genes in adapting to these changing metal
      levels. Current knowledge regarding the mechanisms of metal-regulated gene
      expression and the structural features of sensory metal binding sites are
      described. In addition, the principles governing the ability of the different
      sensors to detect specific metals within a cell to control cytosolic metal levels
      are also discussed. These proteins represent potential targets for the
      development of new therapeutic approaches.

PMID- 21722796
TI  - Inner-city asthma: control can be achieved!

PMID- 21722797
TI  - Recent advances in cytometry applications: preclinical, clinical, and cell
      biology.
AB  - The acceptance of flow cytometry (FCM) in clinical laboratory medicine is a major
      stepping stone towards development new cell analyses, improvement of accuracy,
      and finally a new range of diagnostic tests. Applications range from differential
      blood count determination to the identification of fluorescence-labeled
      subpopulations of disease-specific cell types in cell suspensions. Even new
      disease patterns can be identified by FCM. However, FCM is not only applicable
      for making a diagnosis but also for disease monitoring and routine check-ups. It
      is often used in oncology-related analyses, such as for leukemia and lymphoma
      patients. Here, not only cell numbers are relevant but also the degree of antigen
      expression which can be determined in a standardized way. Next to FCM also image
      cytometry has entered clinical applications although manual review by
      pathologists is still standard. In general, the multicolor approach and hence the
      ability for multiparametric analyses has led FCM to a central cornerstone in cell
      biology research. This review is intended to present an overview of cytometric
      applications which have entered clinical practice and led to deeper understanding
      in biological processes.

PMID- 21722798
TI  - Detection of hematopoietic stem cells by flow cytometry.
AB  - Various studies have been conducted to identify hematopoietic stem cells (HSCs)
      using flow cytometry. The technique is primarily based on fluorochrome-conjugated
      antibodies against cell surface markers of HSCs and the physiological properties
      of HSCs such as high-efflux activity of certain fluorescent dyes. The surface
      marker schemes are based on using c-Kit, Sca-1, and Lineage markers, resulting in
      "KSL" population. Markers in KLS scheme can be used to further subfractionate
      this KLS population to distinguish HSCs from differentiating progenitors. The
      "signaling lymphocyte activation molecule" (SLAM) family of proteins can also be
      used to enhance the KLS enrichment scheme. The other strategy is to identify HSCs
      based on their high efflux ability of fluorescent dyes. This chapter describes
      the method used for identifying the side population (SP) in combination with
      surface markers to isolate HSCs from murine bone marrow and to discuss the
      advantages and pitfalls of this method.

PMID- 21722799
TI  - Identification of very small embryonic/epiblast-like stem cells (VSELs)
      circulating in peripheral blood during organ/tissue injuries.
AB  - We have identified in adult tissues a population of pluripotent very small
      embryonic/epiblast-like stem cells (VSELs) that we hypothesize are deposited at
      onset of gastrulation in developing tissues and play an important role as backup
      population of tissue-specific/committed stem cells. We envision that during
      steady-state conditions these cells may be involved in tissue rejuvenation and in
      processes of regeneration/repair after organ injuries. VSELs similarly as
      epiblast-derived migrating primordial germ cells change the epigenetic signature
      of some of the imprinted genes and therefore remain quiescent in adult tissues.
      These epigenetic changes in methylation status of imprinted genes prevent them
      also from teratoma formation. Mounting evidence indicates that VSELs are
      mobilized into peripheral blood during tissue/organ injuries and enumeration of
      these cells may be of prognostic value (e.g., in stroke or heart infarct). In
      this chapter, we will present FACS-based strategies to detect and enumerate these
      cells in human peripheral blood and umbilical cord blood.

PMID- 21722800
TI  - Apoptosis and beyond: cytometry in studies of programmed cell death.
AB  - A cell undergoing apoptosis demonstrates multitude of characteristic
      morphological and biochemical features, which vary depending on the inducer of
      apoptosis, cell type and the "time window" at which the process of apoptosis is
      observed. Because the gross majority of apoptotic hallmarks can be revealed by
      flow and image cytometry, the cytometric methods become a technology of choice in
      diverse studies of cellular demise. Variety of cytometric methods designed to
      identify apoptotic cells, detect particular events of apoptosis and probe
      mechanisms associated with this mode of cell death have been developed during the
      past two decades. In the present review, we outline commonly used methods that
      are based on the assessment of mitochondrial transmembrane potential, activation
      of caspases, DNA fragmentation, and plasma membrane alterations. We also present
      novel developments in the field such as the use of cyanine SYTO and TO-PRO family
      of probes. Strategies of selecting the optimal multiparameter approaches, as well
      as potential difficulties in the experimental procedures, are thoroughly
      summarized.

PMID- 21722801
TI  - Assessment of oxidative stress-induced DNA damage by immunoflourescent analysis
      of 8-oxodG.
AB  - Oxidative stress refers to the imbalance between the generation of reactive
      oxygen species (ROS) and their scavenging by the inherent antioxidant defenses of
      the cell. The abnormal accumulation of ROS is the underlying pathology in a
      variety of human diseases such as neurodegenerative phenomena, inflammatory
      diseases, metabolic disorders, and cancer. The mechanism by which abnormal
      accumulation of ROS contributes to pathological conditions involves damage or
      oxidative modification of biomolecules, such as nucleotides, lipids, and
      proteins. One of the most common targets of ROS is DNA, modifications of which
      have been associated with cellular transformation and genome instability. There
      are a number of experimental strategies to assess oxidative modification of DNA
      bases, such as chromatography-based assays and indirect immunofluorescence. While
      the former provide quantitative assessment of oxidative modification, the latter
      is a much simpler assay for qualitative determination of DNA base modification in
      very small sample sizes. Here, we present a brief background of the various
      methodologies for the assessment of a specific oxidative DNA modification,
      8oxodG, and present a more detailed account of the indirect immunofluorescence
      assay.

PMID- 21722803
TI  - Fluorescence-based detection and quantification of features of cellular
      senescence.
AB  - Cellular senescence is a spontaneous organismal defense mechanism against tumor
      progression which is raised upon the activation of oncoproteins or other cellular
      environmental stresses that must be circumvented for tumorigenesis to occur. It
      involves growth-arrest state of normal cells after a number of active divisions.
      There are multiple experimental routes that can drive cells into a state of
      senescence. Normal somatic cells and cancer cells enter a state of senescence
      upon overexpression of oncogenic Ras or Raf protein or by imposing certain kinds
      of stress such as cellular tumor suppressor function. Both flow cytometry and
      confocal imaging analysis techniques are very useful in quantitative analysis of
      cellular senescence phenomenon. They allow quantitative estimates of multiple
      different phenotypes expressed in multiple cell populations simultaneously. Here
      we review the various types of fluorescence methodologies including confocal
      imaging and flow cytometry that are frequently utilized to study a variety of
      senescence. First, we discuss key cell biological changes occurring during
      senescence and review the current understanding on the mechanisms of these
      changes with the goal of improving existing protocols and further developing new
      ones. Next, we list specific senescence phenotypes associated with each cellular
      trait along with the principles of their assay methods and the significance of
      the assay outcomes. We conclude by selecting appropriate references that
      demonstrate a typical example of each method.

PMID- 21722804
TI  - Measurement of telomere length using PNA probe by cytometry.
AB  - Peptide nucleic acid (PNA) probes hybridize to denatured telomeric sequences in
      cells permeabilized in hot formamide. In reported protocols, the hybridization
      was conducted in solutions with high formamide concentrations to avoid the DNA
      renaturation that can hamper binding of the oligo-PNA probe to specific
      sequences. We postulated that telomeric DNA, confined in the nuclear microvolume,
      is not able to properly renature after hot formamide denaturation. Therefore, to
      improve hybridization conditions between the probe and the target sequences, it
      might be possible to add probe to sample after the complete removal of formamide.

PMID- 21722802
TI  - Analysis of individual molecular events of DNA damage response by flow- and image
      assisted cytometry.
AB  - This chapter describes molecular mechanisms of DNA damage response (DDR) and
      presents flow- and image-assisted cytometric approaches to assess these
      mechanisms and measure the extent of DDR in individual cells. DNA damage was
      induced by cell treatment with oxidizing agents, UV light, DNA topoisomerase I or
      II inhibitors, cisplatin, tobacco smoke, and by exogenous and endogenous
      oxidants. Chromatin relaxation (decondensation) is an early event of DDR
      chromatin that involves modification of high mobility group proteins (HMGs) and
      histone H1 and was detected by cytometry by analysis of the susceptibility of DNA
      in situ to denaturation using the metachromatic fluorochrome acridine orange.
      Translocation of the MRN complex consisting of Meiotic Recombination 11 Homolog A
      (Mre11), Rad50 homolog, and Nijmegen Breakage Syndrome 1 (NMR1) into DNA damage
      sites was assessed by laser scanning cytometry as the increase in the intensity
      of maximal pixel as well as integral value of Mre11 immunofluorescence. Examples
      of cytometric detection of activation of Ataxia telangiectasia mutated (ATM), and
      Check 2 (Chk2) protein kinases using phospho-specific Abs targeting Ser1981 and
      Thr68 of these proteins, respectively are also presented. We also discuss
      approaches to correlate activation of ATM and Chk2 with phosphorylation of p53 on
      Ser15 and histone H2AX on Ser139 as well as with cell cycle position and DNA
      replication. The capability of laser scanning cytometry to quantify individual
      foci of phosphorylated H2AX and/or ATM that provides more dependable assessment
      of the presence of DNA double-strand breaks is outlined. The new microfluidic Lab
      on-a-Chip platforms for interrogation of individual cells offer a novel approach
      for DDR cytometric analysis.

PMID- 21722805
TI  - Cytometry of intracellular signaling: from laboratory bench to clinical
      application.
AB  - The analysis of signaling pathways based on combinations of phospho-specific
      antibodies is now a well-recognized flow cytometry technique. Despite its wide
      ranging potential in the fields of biology, industry, and medicine, it has been
      relatively slow to gain widespread use, and is often considered to be technically
      challenging. In this chapter, we detail protocols developed in our laboratory for
      monitoring signaling pathways in blood samples based on combinations of phospho
      specific antibodies. Emphasis is placed on clinical application. The assays have
      a modular design, with a core protocol for whole blood fixation and lysis, a
      suite of agents that can acutely activate or inhibit the different signaling
      pathways, and a wide range of phospho-specific antibodies as the readout.

PMID- 21722806
TI  - Immunophenotypic pattern of myeloid populations by flow cytometry analysis.
AB  - We present our experience with immunophenotypic characteristics of benign and
      malignant myeloid populations, with emphasis on differential diagnosis especially
      between eosinophils, dysplastic granulocytes, neoplastic promyelocytes, and
      monocytes. Eosinophils are characterized by bright CD45, high side scatter (SSC),
      very low forward scatter (FSC), positive CD11b, CD11c, CD13, CD15, and CD33. They
      are negative for CD10, CD14, CD16, CD56, CD64, and HLA-DR. Mature monocytes are
      positive for CD11b, CD11c, CD13, CD14, CD33, and CD64, and may express CD2 and
      CD4. Blasts in acute myeloid leukemias (AML) with minimal differentiation have
      low SSC and moderate CD45 expression and are positive for CD34, CD117, CD13, HLA
      DR, and CD33 and may be positive for TdT, CD4, and CD11c. In acute promyelocytic
      leukemia (APL), four FC patterns can be recognized. The majority of cases
      represented classical (hypergranular) APL and were characterized by high SSC,
      positive CD117, usually negative CD34, heterogeneous CD13, and bright CD33
      (pattern 1). The second most common type, corresponding to hypogranular
      (microgranular) variant of APL, differed from classical APL by low SSC and
      frequent coexpression of CD2 and CD34 (pattern 2). Rare cases of APL (pattern3)
      showed mixture of neoplastic cells
      (SSC(low)/CD2(+)/CD13(+)/CD33(+)/CD34(+)/CD117(+)) and prominent population of
      benign granulocytes/maturing myeloid precursors (SSC(high)/CD10(+/
      )/CD16(+/()/CD117(()). One case showed two APL populations, one with hypogranular
      and one with hypergranular characteristics (pattern 4). Detailed phenotypic
      characteristics of neoplastic monocytes and dysplastic granulocytes with their
      differential diagnosis are also presented.

PMID- 21722807
TI  - Flow cytometry-based pharmacodynamic monitoring after organ transplantation.
AB  - Conventional therapeutic drug monitoring based on measuring immunosupressive drug
      concentrations in blood is important in the clinical management of
      immunosuppressive therapy in transplantation medicine. Since rejection or
      infection occurs at irregular drug concentrations immunosuppressive drug therapy
      is often empiric and prophylactic in nature. In addition, blood immunosuppressant
      levels are only indirect predictors of the pharmacologic effects on immune cells,
      because the genetic heterogeneity the immune systems of transplant recipients are
      not equally sensitive to drug effects. Therefore, therapeutic drug monitoring
      requires the application of reliable and effective methods to study the
      pharmacodynamic variability by direct measurements of drug effects on immune cell
      functions. Flow cytometry offers a multiplicity of quantitative analysis
      possibilities, from detection of phosphorylated molecules up to complex
      multicolor analysis of whole blood samples. A large spectrum of flow cytometry
      based applications for pharmacodynamic monitoring is available and allows
      detection and analysis of diverse function of T cells and dendritic cell subsets.
      By combining several assays, it is possible to generate a broad picture of the
      immune status of every single transplanted recipient. Furthermore, it is even
      possible to differentiate between synergistic and antagonistic pharmacodynamic
      effects of immunosuppressive drug combination therapy in vitro and to predict the
      pharmacodynamic drug effects in transplanted recipients. Such a pharmacodynamic
      drug monitoring may offer the opportunity to complete conventional therapeutic
      drug monitoring and, therefore, to tailor immunosuppressive therapy more
      individually.

PMID- 21722808
TI  - Clinical cytometry and progress in HLA antibody detection.
AB  - For most solid organ and selected stem cell transplants, antibodies against
      mismatched HLA antigens can lead to early and late graft failure. In recognition
      of the clinical significance of these antibodies, HLA antibody identification is
      one of the most critical functions of histocompatibility laboratories. Early
      methods employed cumbersome and insensitive complement-dependent cytotoxicity
      assays with a visual read-out. A little over 20 years ago flow cytometry entered
      the realm of antibody detection with the introduction of the flow cytometric
      crossmatch. Cytometry's increased sensitivity and objectivity quickly earned it
      popularity as a preferred crossmatch method especially for sensitized recipients.
      Although a sensitive method, the flow crossmatch was criticized as being "too
      sensitive" as false positive reactions were a know drawback. In part, the
      shortcomings of the flow crossmatch were due to the lack of corresponding
      sensitive and specific HLA antibody screening assays. However, in the mid 1990s,
      solid phase assays, capable of utilizing standard flow cytometers, were
      developed. These assays used microparticles coated with purified HLA molecules.
      Hence, the era of solid-phase, microparticle technology for HLA antibody
      detection was born permitting the sensitive and specific detection of HLA
      antibody. It was now possible to provide better correlation between HLA antibody
      detection and the flow cytometric crossmatch. This flow-based technology was soon
      followed by adaptation to the Luminex platform permitting a mutltiplexed approach
      for the identification and characterization of HLA antibodies. It is hoped that
      these technologies will ultimately lead to the identification of parameters that
      best correlate with and/or predict transplant outcomes.

PMID- 21722809
TI  - Clinical utility of flow cytometry in the study of erythropoiesis and nonclonal
      red cell disorders.
AB  - Erythropoiesis involves proliferation and differentiation of small population of
      hematopoietic stem cells resident in the bone marrow into mature red blood cells.
      The determination of the cellular composition of the blood is a valuable tool in
      the diagnosis of diseases and monitoring of therapy. Flow cytometric analysis is
      increasingly being used to characterize the heterogeneous cell populations
      present in the blood and the hematopoietic cell differentiation and maturation
      pathways of the bone marrow. Here we discuss the role of flow cytometry in the
      study of erythropoiesis and nonclonal red blood cell disorders. First, we discuss
      flow cytometric analysis of reticulocytes. Next, we review salient quantitative
      methods that can be used for detection of fetal-maternal hemorrhage (FMH). We
      also discuss flow cytometric analysis of high hemoglobin F (HbF) in Sickle Cell
      Disease (SCD), hereditary spherocytosis (HS), red cell survival and red cell
      volume. We conclude by discussing cell cycle of erythroid cells.

PMID- 21722810
TI  - Immunophenotypic characterization of bone marrow mast cells in mastocytosis and
      other mast cell disorders.
AB  - Mastocytosis is a term used to designate a heterogeneous group of disorders
      characterized by an abnormal proliferation and accumulation of mast cells (MCs)
      in one or multiple tissues including skin, bone marrow (BM), liver, spleen, and
      lymph nodes, among others. Recent advances in our understanding of mast cell
      biology and disease resulted in the identification of important differences in
      the expression of mast cell surface antigens between normal and neoplastic mast
      cells. Most notably, detection of aberrant expression of CD25 and CD2 on the
      surface of neoplastic mast cells but not on their normal counterparts lead to the
      inclusion of this immunophenotypic abnormality in the World Health Organization
      diagnostic criteria for systemic mastocytosis. Aberrant mast cell surface marker
      expression can be detected in the bone marrow aspirate by flow cytometry, even in
      patients lacking histopathologically detectable aggregates of mast cells in bone
      marrow biopsy sections. These aberrant immunophenotypic features are of great
      relevance for the assessment of tissue involvement in mastocytosis with
      consequences in the diagnosis, classification, and follow-up of the disease and
      in its differential diagnosis with other entities. In this chapter, we provide
      the reader with information for the objective and reproducible identification of
      pathologic MCs by using quantitative multiparametric flow cytometry, for their
      phenotypic characterization, and the criteria currently used for correct
      interpretation of the immunophenotypic results obtained.

PMID- 21722811
TI  - alpha-Linolenic acid intake attenuates myocardial ischemia/reperfusion injury
      through anti-inflammatory and anti-oxidative stress effects in diabetic but not
      normal rats.
AB  - BACKGROUND AND AIMS: Patients with diabetes show enhanced susceptibility to
      myocardial ischemia/reperfusion (MI/R) injury. Epidemiological studies indicated
      that consumption of alpha-linolenic acid (ALA) significantly reduces the risk of
      cardiac events in post-acute myocardial infarction patients. The present study
      attempted to investigate the effects of ALA intake on MI/R injury in normal and
      diabetic rats and its mechanisms. METHODS: The high-fat diet-fed streptozotocin
      (HFD-STZ) rat model was developed. Age-matched normal and HFD-STZ rats were
      randomly assigned to receive normal diet or ALA (oral gavage, 500 MUg/kg per
      day). After 4 weeks of feeding, animals were subjected to 30 min of myocardial
      ischemia and 4 or 6 h of reperfusion. RESULTS: Compared with the normal control,
      HFD-STZ rats showed more severe myocardial functional impairment and injury.
      Although ALA intake for 4 weeks did not change myocardial function and injury in
      normal rats, it significantly improved the instantaneous first derivation of left
      ventricle pressure, reduced infarct size, plasma creatine kinase and lactate
      dehydrogenase activities, and apotosis at the end of reperfusion in HFD-STZ
      diabetic rats. Moreover, ALA intake not only significantly reduced tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations but reduced the
      increase in superoxide production and malonaldialdehyde formation and
      simultaneously enhanced the antioxidant capacity in the diabetic hearts.
      Myocardial PI3K expression and Akt phosphorylation were increased by ALA intake
      in diabetic but not normal rats. CONCLUSIONS: Chronic ALA intake confers
      cardioprotection in MI/R by exerting anti-inflammatory and anti-oxidative stress
      effects in diabetic but not normal rats, which is possibly through PI3K-Akt
      dependent mechanism.

PMID- 21722812
TI  - Hypermethylation-modulated downregulation of RASSF1A expression is associated
      with the progression of esophageal cancer.
AB  - BACKGROUND AND AIMS: Chromosome 3p21 is an important locus harboring critical
      tumor suppressor genes (TSGs) implicated in the pathogenesis of multiple tumors
      including esophageal carcinoma (EC). Aberrant promoter methylation is a
      fundamental mechanism of inactivation of TSGs in cancer. RASSF1A, a candidate
      tumor suppressor gene, recently cloned from the lung tumor locus at 3p21.3, is
      frequently inactivated by hypermethylation of its promoter region in a number of
      malignancies. We undertook this study to investigate the methylation status of
      RASSF1A and its significance in esophageal squamous cell carcinoma (ESCC).
      METHODS: Real-time RT-PCR and real-time methylation-specific PCR (real-time MSP)
      were used to detect RASSF1A expression and the methylation status of the RASSF1A
      promoter, respectively, in 124 primary ESCC tissues. RESULTS: Hypermethylation,
      partial methylation and unmethylation of the promoter region of RASSF1A were
      detected in 56 (45.2%), 23 (18.6%) and 45 (36.2%) of 124 ESCC samples,
      respectively. Unmethylation of the promoter region of RASSF1A was detected in 119
      (96%) of the 124 corresponding noncancerous tissues. Five (4.0%) of 124
      noncancerous tissues showed partial methylation. The presence of hypermethylation
      was statistically associated with loss of RASSF1A mRNA expression in primary ESCC
      (p <0.05). There were statistically significant correlations between the presence
      of hypermethylation and regional lymph node involvement (p=0.000), histological
      differentiation (p=0.009) and tumor stage (p=0.000). CONCLUSIONS: Our results
      suggest that RASSF1A may be one of the ESCC-related TSGs located at 3p21, and
      hypermethylation of the CpG island promoter of the RASSF1A is associated with the
      progression of ESCC.

PMID- 21722813
TI  - Human beta-defensin-2 induction in nasal mucosa after administration of bacterial
      lysates.
AB  - BACKGROUND AND AIMS: The airway epithelium produces antimicrobial peptides (AMPs)
      that prevent colonization of host tissues by a wide range of pathogens. Human
      beta-defensin 2 (hBD-2) is one of the most well-documented AMPs in humans.
      Several bacterial products can induce production of this peptide. Bacterial
      immunostimulants containing bacterial lysates have long been used in the
      treatment of respiratory infections, but their effects on hBD-2 release have not
      been investigated. We undertook this study to induce production of hBD-2 after
      stimulation of the nasal mucosa with bacterial lysates. METHODS: A nasal lavage
      (NL) was performed in 12 healthy volunteers under basal conditions and after a
      nasal challenge with separate and subsequent stimuli with either bacterial
      lysates (20 million), cholecalciferol (400 IU), or sham-challenge with glycerol
      plus isotonic saline solution. Immunohistochemistry was performed in nasal
      biopsies 48 h after stimulation with bacterial lysates to identify the presence
      of hBD-2. RESULTS: Increased levels of hBD-2 (4668.99 +/- 2829.33 pg/mL) were
      measured with ELISA in NL fluids following bacterial challenge. However, hBD-2
      concentrations were below the limit of detection in NL fluids at baseline and
      after the administration of cholecalciferol or the sham-challenge. Through
      immunohistochemistry, hBD-2 was predominantly localized to the epithelium.
      CONCLUSIONS: hBD-2 can be induced in the nasal mucosa after administration of
      bacterial lysates. Stimulation of the innate immune system to produce hBD-2 could
      be used to prevent or even treat infections caused by respiratory pathogens.

PMID- 21722814
TI  - Oxidative stress changes in pregnant patients with and without severe
      preeclampsia.
AB  - BACKGROUND AND AIMS: The etiology of preeclampsia (PE) is unknown and the only
      treatment is removal of the fetus and placenta. The critical changes of this
      state include the increase of vascular resistance and hypoperfusion in the
      uteroplacental microcirculation that predispose to hypoxia and ischemia and,
      therefore, increased oxidative stress through 8-isoprostane, which is
      characterized by damage to the placenta and endothelium. We undertook this study
      to compare oxidative stress in pregnant women with PE. METHODS: A case-control,
      cross-sectional and comparative study was undertaken. Pregnant women between 28
      and 38 weeks of gestation with and without PE were recruited. Venous blood
      samples were taken for determination of 8-isoprostane. Obstetrical variables were
      measured and 8-isoprostane by radioimmunoassay. SPSS v.11 for Windows was used
      for descriptive statistics. Mean +/- standard deviation, correlation and chi(2)
      were used for comparison between groups. RESULTS: We studied 45 patients: 20 with
      PE (44.6%) and 25 without PE (55.4%). The average for 8-isoprostane in
      preeclamptic patients was 699.2 +/- 38.6 pg/dl and without PE was 113.9 +/- 52.4
      pg/dL (p <0.01), gestational age 32.1 +/- 2.6 and 35.1 +/- 1.8 weeks, birth
      weight 1880 +/- 238 g and 2787 +/- 312 g, respectively. Apgar at birth was
      similar in both groups. CONCLUSIONS: We found statistical differences in the 8
      isoprostane levels in both groups. There was no correlation in perinatal results
      in both groups according to 8-isoprostane levels. These results could be the
      basis for the use of antioxidants in the management of PE to counteract tissue
      damage.

PMID- 21722815
TI  - Assessment of serum IL-1, IL-2 and IFN-gamma levels in untreated pulmonary
      tuberculosis patients: role in pathogenesis.
AB  - BACKGROUND AND AIMS: Tuberculosis (Tb) infection is controlled by cell-mediated
      immunity through mediation of IL-1, IL-2 and IFN-gamma. In this study IL-1, IL-2
      and IFN-gamma were determined in serum samples of untreated pulmonary Tb and
      control group including apparently healthy individuals or contacts and normal
      healthy blood donors with an objective of understanding defect(s), if any, in
      synthesis of any of these cytokines that may lead to a diseased state of Tb.
      METHODS: IL-1, IL-2 and IFN-gamma were measured in serum samples of untreated Tb
      patients (n=33), contacts (n=19) and healthy individuals (n=20) by commercially
      available monoclonal antibody-based ELISA. RESULTS: Statistically significant
      differences in IL-1 and IFN-gamma concentrations between groups of pulmonary Tb
      and controls were observed, whereas no significant difference in IL-2 was seen.
      CONCLUSIONS: In the present study, increased levels of cytokines in patients with
      pulmonary Tb are indicative of Th1 response. An increased level of cytokine (IFN
      gamma) in patients with untreated pulmonary Tb appears to be functionally
      defective.

PMID- 21722816
TI  - Contribution of deletion in angiotensin-converting enzyme but not A1166C
      angiotensin II type-1 receptor gene polymorphisms to clinical outcomes in
      atherothrombotic disease.
AB  - BACKGROUND AND AIMS: Angiotensin-converting enzyme insertion/deletion (rs4340)
      and angiotensin II type 1 receptor A1166C (rs5186) gene polymorphisms may be
      involved in coronary heart disease (CHD). This study was designed to evaluate
      potential relationships between these polymorphisms and the risk of long-term all
      cause mortality and major adverse cardiovascular events (MACE) in patients
      requiring revascularization for atherothrombotic disease (ATD) lesions. METHOD:
      This prospective observational study concerned patients referred for supra-aortic
      vessel disease (SVD), CHD, peripheral artery occlusive disease (PAOD) or visceral
      artery disease (VAD). Collected data included ATD referral site, ATD symptoms,
      personal and familial medical histories, ATD extent, vascular risk factors,
      biological values, medication use and rs4340 and rs5186 polymorphisms. The
      primary end point was all-cause mortality. The secondary end point, MACE,
      included cardiovascular death, clinical ischemic event related to SVD, CHD, PAOD
      or VAD. RESULTS: The cohort comprised 956 patients of whom 872 (91.2%) were
      genotyped and followed for 21.1 +/- 9.9 months. Patients were referred for SVD
      (25.9%), CHD (42.3%), PAOD (35.2%) or VAD (1.6%). All-cause mortality and MACE
      rates were 7.6 and 27.2%, respectively. When comparing I/D + D/D vs. I/I
      genotypes, rs4340 polymorphism was associated with higher all-cause mortality
      rates according to uni- and multivariate analyses (p=0.008 and 0.011,
      respectively). Other differences were not significant (rs4340 polymorphism and
      MACE, rs5186 polymorphism and all-cause mortality and MACE). No interaction was
      found between the polymorphisms. Other independent predictors of all-cause
      mortality included PAOD history, SVD history, body mass index <25 kg/m(2),
      HbA(1c) >=6.5%, absence of dyslipidemia and no use of aspirin. CONCLUSION: rs4340
      polymorphism is associated with long-term all-cause mortality in advanced ATD
      patients requiring revascularization, whereas rs5186 polymorphism does not.

PMID- 21722817
TI  - Atherogenic lipid profile in Behcet's disease: evidence of alteration of HDL
      subclasses.
AB  - BACKGROUND AND AIMS: Behcet's disease (BD) is an inflammatory vasculitis, most
      common in the Mediterranean area and Asia. Evidence for accelerated
      atherosclerosis in BD has been observed. The relationship between cardiovascular
      risk factors and accelerated atherosclerosis in patients with BD is still
      controversial. The aim of this study was to evaluate the lipid profile and to
      investigate the low-density lipoprotein (LDL) size and the distribution of high
      density lipoprotein (HDL) subpopulations in BD patients. METHODS: Thirty six BD
      patients were compared to 36 healthy controls. Total cholesterol (TC),
      triglycerides (TG) and HDL-cholesterol (HDL-C) levels were measured using
      standard techniques. HDL subclasses and LDL-C size were estimated using
      polyacrylamide linear gradient gel electrophoresis. The LDL-C/HDL-C ratio was
      also calculated. High-sensitive C-reactive protein (hsCRP) level was measured by
      a turbidimetric method. Homocysteine (Hcy) level was determined using a liquid
      chromatography tandem mass spectrometry (LC/MS/MS). RESULTS: In BD patients, HDL
      C levels as well as its subfraction levels were decreased (respectively, p <10(
      6) and p <10(-3)). Percentage of HDL2 subpopulation was also decreased (p=0.02).
      HDL3 subfraction was significantly higher (p=0.02). The LDL-C/HDL-C ratio and CRP
      level were increased (respectively, p=10(-4) and p=0.003). TC was correlated with
      CRP. HDL-C and its subfractions were correlated with CRP and TG levels. HDL
      subparticle percentages were also correlated with age. CONCLUSIONS: Our findings
      of a reduction of HDL-C and HDL2 subpopulation and an increase HDL3 subclass and
      a higher LDL-C/HDL-C ratio may be considered as important predictors of
      cardiovascular events in BD patients.

PMID- 21722818
TI  - Lower serum paraoxonase-1 activity is related to higher serum amyloid a levels in
      metabolic syndrome.
AB  - BACKGROUND AND AIMS: High-density lipoproteins (HDL) contain the anti-oxidative
      enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute
      phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may
      impair PON-1 activity, whereas SAA and PON-1 are reciprocally regulated in
      response to acute inflammatory stimuli. The relationship of serum PON-1 activity
      with SAA during low-grade chronic inflammation is unclear. Here we tested the
      extent to which low serum PON-1 activity is related to high SAA levels in
      subjects with and without metabolic syndrome (MetS). METHODS: In 19 nondiabetic
      subjects with MetS and 67 subjects without MetS, serum PON-1, assayed as its
      arylesterase activity, and SAA were measured together with plasma lipids and
      lipoproteins, high-sensitive C-reactive protein (hs-CRP) and insulin resistance
      (homeostasis model assessment (HOMA(ir)). RESULTS: PON-1 activity was decreased
      (p=0.023), whereas SAA levels were increased (p=0.042) in MetS subjects,
      coinciding with higher hs-CRP levels and HOMA(ir) values. Multiple linear
      regression analysis revealed that age- and gender-adjusted PON-1 activity was
      related inversely to SAA (beta=-0.256, p=0.020) after adjustment for MetS, or
      alternatively for hs-CRP and HOMA(ir) (beta=-0.271, p=0.049). CONCLUSIONS:
      Decreased serum PON-1 activity in MetS may in part be attributable to higher SAA
      levels. We suggest that higher SAA levels contribute to impaired HDL anti
      oxidative function in MetS via an effect on PON-1 regulation.

PMID- 21722819
TI  - Genetic polymorphism of DNA base-excision repair genes (APE1, OGG1 and XRCC1) and
      their correlation with risk of lung cancer in a Chinese population.
AB  - BACKGROUND AND AIMS: Reactive oxygen species (ROS) and numerous carcinogens may
      cause DNA damage including oxidative base lesions that contribute to the risk of
      lung cancer. The base excision repair (BER) pathway could effectively remove
      oxidative lesions in which 8-oxoguanine glycosylase-1 (OGG1), x-ray repair cross
      complementing 1 (XRCC1), and apurinic/apyimidinic endonuclease 1 (APE1) play key
      roles. The aim of this study was to analyze the polymorphisms of DNA BER genes
      (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects
      of these variants, with risk of lung cancer. METHODS: In a hospital-based, case
      control study of 455 lung cancer cases and 443 cancer-free hospital controls, the
      SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were
      genotyped and analyzed for their correlation with the risk of lung cancer in
      multivariate logistic regression models. RESULTS: Individuals homozygous for the
      variants APE1 -141GG showed a protective effect for lung cancer overall (OR=0.62;
      95% CI: 0.42-0.91; p=0.02) and for lung adenocarcinoma (OR=0.65; 95% CI, 0.44
      0.96; p=0.03). When analyzing the combined effects of variant alleles, 84
      patients and controls were identified who were homozygous for two or three of the
      potential protective alleles (i.e., OGG1 326Cys, XRCC1 399Gln and APE1 -141G).
      ORs were significantly reduced when all patients were analyzed (OR=0.62; 95% CI:
      0.38-0.99; p=0.05). CONCLUSIONS: The combined effects of polymorphisms within BER
      genes may contribute to the tumorigenesis of lung cancer.

PMID- 21722820
TI  - Association between CTLA-4 exon-1 +49A>G polymorphism and primary biliary
      cirrhosis risk: a meta-analysis.
AB  - BACKGROUND AND AIMS: CTLA-4 exon-1 +49A>G polymorphisms have been reported to
      influence the risk for primary biliary cirrhosis in many studies; however, the
      results still remain controversial and ambiguous. The aim of this study was to
      determine more precise estimations for the relationship between CTLA-4 exon-1
      +49A>G polymorphisms and the risk for primary biliary cirrhosis. METHODS:
      Electronic searches for all publications were conducted on associations between
      this variant and breast cancer in several databases through November 2010. Crude
      odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate
      the strength of the association. Eight studies were identified including 2151
      cases and 2214 controls. RESULTS: Overall, there were no significant associations
      between CTLA +49G>A polymorphism and primary biliary cirrhosis risk (codominant
      model: GA vs. AA OR=1.190, 95% CI=0.818-1.732; GG vs. AA OR=1.153, 95% CI=0.858
      1.550; dominant model: OR=1.181, 95% CI=0.873-1.599; and recessive model:
      OR=1.148; 95% CI=0.903-1.459). In the subgroup analysis by ethnicity, a
      significantly increased risk was found for Asians (GG vs. AA OR=1.873; 95%
      CI=1.202-2.921) and recessive model (OR=1.758; 95% CI = 1.271-2.433). In the
      stratified analysis by control sources, significant association were observed in
      population-based studies (GA vs. AA OR=1.432; 95% CI=1.078-1.902). CONCLUSIONS:
      This meta-analysis suggests that the CTLA-4 +49G>A polymorphism may be a risk
      factor for primary biliary cirrhosis in Asians.

PMID- 21722821
TI  - Meta-analysis of MMP2 -1306T allele as a protective factor in digestive cancer.
AB  - BACKGROUND AND AIMS: Matrix metalloproteinase-2 (MMP-2) is an enzyme with
      proteolytic activity on matrix proteins and abolishes a Sp-1 binding site and
      consequently decreases its activity. Many studies have been carried out on the
      association between MMP2 -1306C/T polymorphism and digestive cancer risk, but
      results were somewhat controversial and underpowered. METHODS: To examine the
      risk of digestive cancer associated with -1306C/T polymorphism of MMP2, we
      performed a meta-analysis of ten case-control studies. Eligible studies were
      identified by searching the electronic literature using Pubmed and Embase. Odds
      ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the
      association. RESULTS: Overall, we found that -1306T allele can decrease digestive
      cancer risk in three different genotype models (T-allele vs. C-allele, OR=0.73,
      95% CI: 0.54-0.98, p=0.034; TC vs. CC, OR=0.64, 95% CI: 0.53-0.78, p <0.001;
      TT+TC vs. CC, OR=0.68, 95% CI: 0.53-0.86, p=0.002). Similarly, in the stratified
      analysis by cancer type, ethnicity and source of control, significantly decreased
      cancer risk was indicated. Moreover, in the subgroup of smokers, -1306T allele
      may protect people against digestive cancer risk (TT+TC vs. CC, OR=0.71, 95% CI:
      0.51-0.98, p=0.037). CONCLUSIONS: Our meta-analysis showed evidence that MMP2 
      1306T allele may be a protective factor for digestive cancer risk as well as a
      low-penetrance susceptibility digestive cancer biomarker.

PMID- 21722822
TI  - Contribution of serum leptin to metabolic syndrome in obese and nonobese
      subjects.
AB  - BACKGROUND AND AIMS: Little evidence exists regarding the association of leptin
      with metabolic syndrome (MetS) as defined by conventional criteria. Moreover, the
      contribution of obesity to this relationship is not well understood. This study
      aimed to evaluate the association between leptin concentrations with MetS in
      obese and nonobese subjects. METHODS: Data from the Third National Surveillance
      of Risk Factors of Non-Communicable Diseases (SuRFNCD) in Iran was used. In a
      cross-sectional study of 3045 adults (48.2% men) aged 25-64 years, anthropometric
      indices, blood pressure, fasting plasma glucose, fasting insulin, lipid profile
      [triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C) and triglycerides], and fasting leptin were
      measured. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also
      calculated. RESULTS: Leptin concentrations were 2.6 fold higher in women compared
      with men. Subjects with MetS had significantly higher leptin concentrations.
      Leptin concentrations increased steadily with an increment in the number of MetS
      components (p <0.001). Leptin was significantly associated with MetS after
      adjustment for age, cigarette smoking, medication use, physical activity, HOMA
      IR, and LDL-C. The significant association between leptin and MetS persisted
      after adjustment for body mass index (OR: 1.31, 95% CI: 1.09-1.58 in males and
      1.17, 95% CI: 1.01-1.38 in females) and waist circumference (OR: 1.24 95% CI:
      1.01-1.51 in men and 1.22, 95% CI: 1.04-1.43 in women). After dividing subjects
      into obese and nonobese, leptin concentrations were again significantly higher in
      subjects with MetS in both groups. CONCLUSIONS: We demonstrated that leptin
      concentrations are significantly associated with International Diabetes
      Federation (IDF)-defined MetS, independent of overall and central obesity. Our
      findings point to an independent role for leptin in development of MetS.

PMID- 21722823
TI  - Preliminary phytochemical screening and in vitro anti-Helicobacter pylori
      activity of acetone and aqueous extracts of the stem bark of Sclerocarya birrea
      (Anacardiaceae).
AB  - Helicobacter pylori antibiotic resistance and other problems associated with
      combination therapy have generated a considerable interest in the search for
      alternative therapeutic agents. In order to identify novel sources of such
      agents, the antimicrobial activity of five solvent extracts of the stem bark of
      Sclerocarya birrea was investigated against 30 clinical strains of H. pylori and
      a reference strain NCTC 11638 using standard microbiological techniques.
      Metronidazole and amoxicillin were included in these experiments as positive
      control antibiotics. The active phytocomponents were detected by TLC and indirect
      bioautography. All the extracts exhibited anti-H. pylori activity with zone
      diameters of inhibition between 0 and 21 mm. The acetone and aqueous extracts
      showed potent anti-H. pylori activity with minimum inhibitory concentration
      (MIC(90)) values ranging from 0.06-2.50 mg/mL, whereas those for the control
      antibiotics ranged from 0.001-5.0 mg/mL. The acetone extract was highly
      bactericidal at 1.2 mg/mL with complete elimination of the organisms within 18 h.
      The activity of both acetone and aqueous extracts was better than metronidazole
      (p<0.05). Most of the active phytocomponents were located in the acetone extract;
      R(f)<=0.62 with >90% inhibition. These results demonstrate that the acetone and
      aqueous extracts of S. birrea may contain compounds with therapeutic activity;
      therefore, they may represent potential sources of new anti-H. pylori regimen.

PMID- 21722824
TI  - Does the expression of versican isoforms contribute to the pathogenesis of
      neurodegenerative diseases?
AB  - Classical neurodegenerative diseases such as Alzheimer's, Parkinson's, and
      Huntington's are most commonly seen in older persons. The incidence rate
      increases as life expectancy increases. Even though neuronal loss, neuronal death
      and accumulated toxic proteins are well investigated, the mechanism(s) of
      neurodegenerative disorders is not yet fully understood. Versican is a large
      extracellular matrix proteoglycan. Its isoforms are aberrantly expressed in
      central nervous system injuries. Diverse lines of evidence suggest that versican
      isoforms play a vital role in regulating neuronal differentiation, maturation,
      neurite outgrowth, and synaptic transmission. Some toxic proteins may be
      increased and less sensitive to degeneration due to the chondroitin sulfate (CS)
      chains of versicans. We propose that the patterns of versican V1 and V2 isoforms
      act as a fine-tuned mechanism for guiding the change of neural microenvironment,
      and the unbalanced expression of V1 and V2 isoforms may contribute to the
      pathogenesis of neurodegenerative diseases. The emergence of versican isoforms
      indicates that it may explain the pathogenesis of the common sporadic forms of
      complex diseases.

PMID- 21722826
TI  - Invited commentary.

PMID- 21722827
TI  - Invited commentary.

PMID- 21722828
TI  - Invited commentary.

PMID- 21722829
TI  - Invited commentary.

PMID- 21722830
TI  - Silent cerebral events in asymptomatic carotid stenosis.
AB  - BACKGROUND: Approximately 20% of strokes are attributable to carotid stenosis.
      However, the number of asymptomatic patients needed to prevent one stroke or
      death with endarterectomy is high at 17 to 32. There is a clear need to identify
      asymptomatic individuals at high risk of developing future ischemic events to
      improve the cost-effectiveness of surgery. Our aim was to examine the evidence
      for subclinical microembolization and silent brain infarction in the prediction
      of stroke in asymptomatic carotid stenosis using transcranial Doppler (TCD),
      computed tomography (CT), and magnetic resonance imaging (MRI). METHODS: The
      review was conducted according to the preferred reporting items for systematic
      reviews and meta-analyses (PRISMA) guidelines. Articles regarding humans between
      1966 and 2010 were identified through systematic searches of Pubmed, MEDLINE, and
      EMBASE electronic databases using a predetermined search algorithm. RESULTS:
      Fifty-eight full text articles met the inclusion criteria. A median of 28% of
      microemboli positive patients experienced a stroke or transient ischemic attack
      during follow-up compared with 2% of microemboli negative patients (P = .001).
      The same was true for the end point of stroke alone with a median of 10% of
      microemboli positive patients experiencing a stroke vs 1% of microemboli negative
      patients (P = .004). A specific pattern of silent CT infarctions was related to
      future stroke risk (odds ratio [OR] = 4.6; confidence interval [CI] = 3.0-7.2; P
      < .0001). There are no prospective MRI studies linking silent infarction and
      stroke risk. CONCLUSIONS: There is level 1 evidence for the use of TCD to detect
      microembolization as a risk stratification tool. However, this technique requires
      further investigation as a stroke prevention tool and would be complemented by
      improvements in carotid plaque imaging.

PMID- 21722831
TI  - Patient-originated futility insight: ethical right or ethical plight?

PMID- 21722832
TI  - Debate regarding the best surgical option for type IV thoracoabdominal aortic
      aneurysms.
AB  - Conventional open surgical repair, endovascular treatment, and the hybrid
      technique constitute the three treatment options for patients with type IV
      thoracoabdominal aortic aneurysms (TAAAs). Treatment is advocated to prevent
      rupture but yields significant risk for spinal cord ischemia, cardiovascular, and
      renal and respiratory complications, including death. Refinements in open
      surgical techniques and branched endovascular graft repair together with the
      development of hybrid techniques have been applied to the treatment of type IV
      TAAAs to decrease the risk of these complications. However, much of the evidence
      of the argument is circumstantial. Large experiences are limited to a few centers
      worldwide with inherent disparity between patient groups and several limitations
      to the construction of a prospective randomized trial. This controversial subject
      is now open to discussion, and our debaters have been given the challenge to
      clarify the evidence to justify their preferred option for repair of type IV
      TAAAs.

PMID- 21722833
TI  - Editors' commentary.

PMID- 21722837
TI  - Regarding "stroke and death after carotid endarterectomy and carotid artery
      stenting with and without high risk criteria".

PMID- 21722838
TI  - Regarding "aneurysmal iliac arteries do not portend future iliac aneurysmal
      enlargement after endovascular aneurysm repair for abdominal aortic aneurysm".

PMID- 21722840
TI  - Regarding the commentary for "novel sutureless telescoping anastomosis
      revascularization technique of supra-aortic vessels to simplify combined open
      endovascular procedures in the treatment of aortic arch pathologies".

PMID- 21722841
TI  - Asthma phenotypes in childhood.

PMID- 21722842
TI  - The obesity phenotype in children with asthma.
AB  - Asthma and obesity have been increasing in prevalence internationally among
      children. Evidence points to an association between these chronic morbidities,
      suggesting the development of an 'obese asthma' phenotype in childhood. This
      review summarises the evidence that the proinflammatory environment created by
      excess adiposity may provide a mechanism leading to obese asthma in children and
      adolescents. Weight loss studies conducted in children without asthma have
      demonstrated a reduction in systemic inflammation. However, the impact of weight
      loss in the obese paediatric population with asthma has not been investigated.
      The paucity of information highlights the need for high quality randomised
      controlled trials of weight loss in this population that include assessment of
      systemic and airway inflammation, and clinical asthma outcomes. This will lead to
      refinements in management approaches for these patients.

PMID- 21722843
TI  - Episodic viral wheeze and multiple trigger wheeze in preschool children: a useful
      distinction for clinicians?
AB  - Accumulating evidence suggest that splitting preschool recurrent wheezing
      disorders into Episodic (Viral) Wheeze (EVW) and Multiple Trigger Wheeze (MTW) is
      an oversimplification. There is little evidence that the EVW and MTW phenotypes
      are related to the longitudinal patterns of wheeze, or to different underlying
      pathological processes. As the clinical response to inhaled corticosteroids and
      montelukast varies considerably between individual children with EVW, and between
      individual patients with MTW, the clinical usefulness of the EVW-MTW approach is
      doubtful. Based on the currently available evidence, we propose to describe
      preschool wheeze symptoms not only in terms of temporal pattern, but also in
      terms of frequency and severity, and age of onset. Relevant associated clinical
      parameters like atopy and eczema should be described with recognition of age of
      onset, pattern, and severity. Comparing these data to biomarkers and
      histopathology may help to improve our understanding of preschool wheezing
      disorders in the future. Until phenotypes can be described that are associated
      with different pathobiological process, are related to different longitudinal
      outcomes, or are clearly different in terms of response to therapy, clinicians
      are encouraged to take a trial and error approach of different therapeutic agents
      in preschool children with troublesome recurrent wheeze.

PMID- 21722844
TI  - Inflammatory phenotypes in stable and acute childhood asthma.
AB  - Asthma is a complex disease with a significant inflammatory component
      characterized by repeated episodes of exacerbation and inflammatory changes in
      both large and peripheral airways. The clinical course of childhood asthma varies
      substantially among individuals. The reasons why the clinical course of asthma
      displays persistence and even progression in some children but is intermittent in
      others remains unclear. Children with asthma are different from adults with
      asthma. Inflammatory involvement in children with asthma appears to be localised
      more in peripheral than central airways, and the inflammatory phenotype displays
      differences from adults. Children with acute asthma display a dominant
      eosinophilic inflammatory phenotype instead of the neutrophilic phenotype that is
      seen in adults with acute asthma. Corticosteroids do not alter the natural
      history of the disease and may not prevent progressive decline of lung function
      in the subset of severe asthma. The underlying inflammatory mechanisms involved
      in the decline of lung function remains to be elucidated. Non-invasive biomarkers
      for monitoring lung function and inflammation are needed in children to track and
      monitor pathological changes in the distal airways, as is the development of
      therapeutic strategies that effective to peripheral airway in this vulnerable
      population. This review summarises our present understanding of airway
      inflammatory phenotypes in children with asthma and factors determining disease
      severity in exacerbations of asthma, and focuses on studies evaluating
      relationships between clinical features and the dominant inflammatory phenotypes
      in disease prognosis in a variety of asthma populations. This presents the
      crucial steps for describing the strategies associated with improvements for
      paediatric asthma care.

PMID- 21722845
TI  - Steroid responsiveness and wheezing phenotypes.
AB  - Oral corticosteroids are the cornerstone of management of acute moderate or
      severe asthma whilst preventive inhaled corticosteroids are the mainstay of the
      preventive management of children with asthma. Yet, variation in the magnitude of
      response to corticosteroids has been observed. There is increasing evidence that
      preschool-aged children with viral-induced asthma may display a certain degree of
      corticosteroid resistance, requiring higher doses of corticosteroids to overcome
      it. The identification of determinants of responsiveness is complicated by design
      issues, including heterogeneous populations of children with asthma and
      bronchiolitis or of children with viral-induced and multi-trigger asthma
      phenotypes in published trials. Potential key determinants of responsiveness may
      include age, trigger, phenotype, tobacco smoke exposure and genotype. The
      mechanistic pathway for corticoresistance may originate from a gene-environment
      interaction, leading to non-eosinophilic airway inflammation. The clinician
      should carefully confirm the diagnosis of asthma and ascertain the phenotype to
      select appropriate phenotype-specific therapy.

PMID- 21722846
TI  - Phenotypes of refractory/severe asthma.
AB  - The acid test of phenotyping is that it leads either to a clinically useful or
      mechanistically important insight. Phenotypes may change over time, but the exact
      definition of a phenotype shift is unclear. Methods of phenotyping are either
      investigator driven, in which a priori prejudices are applied to the data, or
      (semi) objective, in which mathematical techniques or systems biology approaches
      are applied to the dataset. However, the composition of the dataset is driven by
      investigator prejudice. Phenotyping is likely most useful in severe asthma,
      because mild and moderate asthma responds to simple treatments, and no great
      subtlety is required. Our non-evidence based approach is to define the
      subpopulation of genuine severe, therapy-resistant asthmatics from the generality
      of problematic severe asthma. We then investigate them invasively with
      bronchoscopy and a steroid trial using intramuscular triamcinolone to determine
      the nature of any inflammatory process; whether inflammation and symptoms are
      concordant or discordant; whether the inflammatory process is steroid resistant
      or sensitive; and whether the child has persistent airflow limitation. Other
      possibly relevant phenotypes include the child with severe exacerbations; brittle
      asthma; and severe asthma with fungal sensitization. Severe, therapy resistant
      asthma is a disparate disease, and only international uniform approaches,
      carefully characterising the children as a prelude to focussed clinical trials
      will allow progress to be made, and vindicate (or otherwise) our suggested
      approach.

PMID- 21722847
TI  - Pulmonary infections and community associated methicillin resistant
      Staphylococcus aureus: a dangerous mix?
AB  - The incidence of complicated pneumonias in children is increasing with a
      concurrent increase in the incidence of community-associated methicillin
      resistant Staphylococcus aureus (CA-MRSA) infections. CA-MRSA is distinct from
      hospital associated MRSA [HA-MRSA] in regards to its genotype, epidemiology, and
      clinical course. Unlike HA-MRSA, CA-MRSA often strikes young, previously healthy
      children. Pneumonias caused by CA-MRSA have a rather distinct presentation.
      Because of its pore-forming toxins, namely Panton-Valentine leukocidin (PVL) and
      alpha-hemolysin, extensive necrotizing disease with corresponding hypoxaemia and
      hypercarbia is common. Other features include multilobar disease, leucopenia,
      haemoptysis, and high mortality rates. A previous influenza-like illness or skin
      and soft tissue infection [SSTI] often precede the development of pneumonia due
      to CA-MRSA. Vancomycin is recommended as first-line empiric therapy for suspected
      CA-MRSA infections. However, vancomycin is not an ideal agent for the treatment
      of pneumonia given its poor concentrating ability in alveolar fluid. Linezolid
      and clindamycin have also been used in the treatment of CA-MRSA pneumonia and
      ongoing research is looking for alternative antimicrobials. Recent studies have
      continued to report a lack of correlation between nasal colonization and active
      infections due to CA-MRSA. Given that the role of nasal colonization in CA-MRSA
      infection is not clear, the utility of decolonization treatment has been a point
      of debate. Finally, patients with cystic fibrosis are becoming increasingly
      colonized with MRSA as opposed to MSSA. There is some accumulating evidence that
      patients with MRSA show a more rapid deterioration in their degree of obstructive
      disease as measured by forced expiratory volume in one second (FEV(1)). However,
      it still is not clear whether MRSA is a marker for worsening disease or whether
      it actually is a cause of disease progression in cystic fibrosis. More
      longitudinal data is needed to understand how MRSA colonization impacts the
      course of disease in cystic fibrosis.

PMID- 21722848
TI  - The role of rigid and flexible bronchoscopy in children.
AB  - Bronchoscopy for paediatric respiratory disease is a routine procedure in
      paediatric pulmonology. Rigid bronchoscopy is now much less commonly used than
      flexible bronchoscopy. Technological advances have brought better picture quality
      and easier storage of video documentation. Indications with clear clinical
      benefit are congenital or acquired unexplained airway obstruction. In pulmonary
      infections or infiltrates in immunodeficient or immunosuppressed children not
      responding to empirical treatment a pathogen may be identified by bronchoscopy
      and bronchoalveolar lavage (BAL). Bronchoscopy and BAL can be indicated in
      children with unusual presentations of chronic cough or wheeze, and cystic
      fibrosis. The use of transbronchial biopsies (TBB) is established in paediatric
      lung transplantation. New applications and techniques are being developed, such
      as endobronchial ultrasound and transbronchial needle biopsy of lymph nodes and
      the role of airway stent placement have become better understood.

PMID- 21722849
TI  - Current methods of non-invasive ventilatory support for neonates.
AB  - Non-invasive ventilatory support can reduce the adverse effects associated with
      intubation and mechanical ventilation, such as bronchopulmonary dysplasia,
      sepsis, and trauma to the upper airways. In the last 4 decades, nasal continuous
      positive airway pressure (CPAP) has been used to wean preterm infants off
      mechanical ventilation and, more recently, as a primary mode of respiratory
      support for preterm infants with respiratory insufficiency. Moreover, new methods
      of respiratory support have been developed, and the devices used to provide non
      invasive ventilation (NIV) have improved technically. Use of NIV is increasing,
      and a variety of equipment is available in different clinical settings. There is
      evidence that NIV improves gas exchange and reduces extubation failure after
      mechanical ventilation in infants. However, more research is needed to identify
      the most suitable devices for particular conditions; the NIV settings that should
      be used; and whether to employ synchronized or non-synchronized NIV. Furthermore,
      the optimal treatment strategy and the best time for initiation of NIV remain to
      be identified. This article provides an overview of the use of non-invasive
      ventilation (NIV) in newborn infants, and the clinical applications of NIV.

PMID- 21722850
TI  - Using reference values to interpret pulmonary function tests.

PMID- 21722851
TI  - Poster presentation - a visual medium for academic and scientific meetings.
AB  - Academic poster presentations are used as a medium of knowledge transfer by a
      wide range of health professional groups. Posters also provide a means of
      publication for academic and professional contributors. Posters are designed to
      give a visual representation of an issue that firstly attracts attention, and
      then conveys an intended message. Whilst the poster medium has become adopted
      into the publication orthodoxy of the scientific and academic communities, there
      are acknowledged limitations regarding the depth of knowledge transfer, issues of
      compilation and production, and the related viewer conception. If treated as a
      standalone medium, the limitations of a two-dimensional, page limited format may
      not provide the ideal opportunity to deliver the depth of information required
      within the academic context. Despite these limitations however, the continued use
      of posters is justified when supported by author presentation or multi-media
      resources. This paper aims to provide an overview of the current concept and
      practicality of academic poster publications. It also outlines by example, some
      of the wider principles of poster compilation and presentation, for use by those
      who may utilise the medium at academic and scientific meetings.

PMID- 21722852
TI  - The Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Expert
      Consensus Statement on the perioperative management of patients with implantable
      defibrillators, pacemakers and arrhythmia monitors: facilities and patient
      management: executive summary this document was developed as a joint project with
      the American Society of Anesthesiologists (ASA), and in collaboration with the
      American Heart Association (AHA), and the Society of Thoracic Surgeons (STS).

PMID- 21722853
TI  - Guidance for the Heart Rhythm Society pertaining to interactions with industry
      endorsed by the Heart Rhythm Society on April 26, 2011.

PMID- 21722854
TI  - Rebuttal to M cells are not present in the ventricular myocardium. Point.

PMID- 21722855
TI  - Rebuttal to M cells are present in the ventricular myocardium. Counterpoint.

PMID- 21722856
TI  - The Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Expert
      Consensus Statement on the perioperative management of patients with implantable
      defibrillators, pacemakers and arrhythmia monitors: facilities and patient
      management this document was developed as a joint project with the American
      Society of Anesthesiologists (ASA), and in collaboration with the American Heart
      Association (AHA), and the Society of Thoracic Surgeons (STS).

PMID- 21722857
TI  - [Subclinical thyroid dysfunction in pregnancy].

PMID- 21722858
TI  - Disruption of PTPRO causes childhood-onset nephrotic syndrome.
AB  - Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of
      disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it
      typically results in end-stage kidney disease, the steroid-resistant subtype
      (SRNS) of INS is especially important when it occurs in children. The present
      study included 29 affected and 22 normal individuals from 17 SRNS families;
      genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by
      homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was
      identified in one consanguineous family with two affected siblings. Direct
      sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as
      glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor
      splice-site mutation. This mutation causes skipping of the evolutionarily
      conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry
      with GLEPP1 antibody showed a similar staining pattern in the podocytes of the
      diseased and control kidney tissues. We used a highly polymorphic intragenic DNA
      marker-D12S1303-to search for homozygosity in 120 Turkish and 13 non-Turkish
      individuals in the PodoNet registry. This analysis yielded 17 candidate families,
      and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was
      further identified via DNA sequencing in a second Turkish family. This mutation
      causes skipping of exon 19, and this introduces a premature stop codon at the
      very beginning of exon 20 (p.Asn888Lysfs*3) and causes degradation of mRNA via
      nonsense-mediated decay. Immunohistochemical analysis showed complete absence of
      immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process
      fusion and extensive microvillus transformation of podocytes, were observed via
      electron microscopy in both families. The present study introduces mutations in
      PTPRO as another cause of autosomal-recessive nephrotic syndrome.

PMID- 21722860
TI  - Another reason to blush: unilateral electroconvulsive therapy (ECT).

PMID- 21722859
TI  - Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic
      protein, causes human progressive hearing loss DFNA64.
AB  - SMAC/DIABLO is a mitochondrial proapoptotic protein that is released from
      mitochondria during apoptosis and counters the inhibitory activities of inhibitor
      of apoptosis proteins, IAPs. By linkage analysis and candidate screening, we
      identified a heterozygous SMAC/DIABLO mutation, c.377C>T (p.Ser126Leu, refers to
      p.Ser71Leu in the mature protein) in a six-generation Chinese kindred
      characterized by dominant progressive nonsyndromic hearing loss, designated as
      DFNA64. SMAC/DIABLO is highly expressed in human embryonic ears and is enriched
      in the developing mouse inner-ear hair cells, suggesting it has a role in the
      development and homeostasis of hair cells. We used a functional study to
      demonstrate that the SMAC/DIABLO(S71L) mutant, while retaining the proapoptotic
      function, triggers significant degradation of both wild-type and mutant
      SMAC/DIABLO and renders host mitochondria susceptible to calcium-induced loss of
      the membrane potential. Our work identifies DFNA64 as the human genetic disorder
      associated with SMAC/DIABLO malfunction and suggests that mutant
      SMAC/DIABLO(S71L) might cause mitochondrial dysfunction.

PMID- 21722861
TI  - Evaluation of cardiac arrhythmia among athletes.

PMID- 21722862
TI  - The impact of the aging population on coronary heart disease in the United
      States.
AB  - BACKGROUND: The demographic shift toward an older population in the United States
      will result in a higher burden of coronary heart disease, but the increase has
      not been quantified in detail. We sought to estimate the impact of the aging US
      population on coronary heart disease. METHODS: We used the Coronary Heart Disease
      Policy Model, a Markov model of the US population between 35 and 84 years of age,
      and US Census projections to model the age structure of the population between
      2010 and 2040. RESULTS: Assuming no substantive changes in risks factors or
      treatments, incident coronary heart disease is projected to increase by
      approximately 26%, from 981,000 in 2010 to 1,234,000 in 2040, and prevalent
      coronary heart disease by 47%, from 11.7 million to 17.3 million. Mortality will
      be affected strongly by the aging population; annual coronary heart disease
      deaths are projected to increase by 56% over the next 30 years, from 392,000 to
      610,000. Coronary heart disease-related health care costs are projected to rise
      by 41% from $126.2 billion in 2010 to $177.5 billion in 2040 in the United
      States. It may be possible to offset the increase in disease burden through
      achievement of Healthy People 2010/2020 objectives or interventions that
      substantially reduce obesity, blood pressure, or cholesterol levels in the
      population. CONCLUSIONS: Without considerable changes in risk factors or
      treatments, the aging of the US population will result in a sizeable increase in
      coronary heart disease incidence, prevalence, mortality, and costs. Health care
      stakeholders need to plan for the future age-related health care demands of
      coronary heart disease.

PMID- 21722863
TI  - Seizure with acute pulmonary infiltrates.

PMID- 21722864
TI  - Severe circadian hypertension in a young man.

PMID- 21722865
TI  - Cutaneous immunoglobulin G4-related systemic disease.

PMID- 21722866
TI  - Troponins and electroconvulsive therapy (ECT): caution in reporting results.

PMID- 21722868
TI  - Improving cardiac rehabilitation referral patterns using computerized physician
      order entry systems.

PMID- 21722869
TI  - Human epididymis protein 4 offers superior specificity in the differentiation of
      benign and malignant adnexal masses in premenopausal women.
AB  - OBJECTIVE: We sought to assess the ability of human epididymis protein 4 (HE4)
      and CA-125 to distinguish among benign, borderline, and malignant pelvic masses
      in premenopausal women. STUDY DESIGN: We conducted a subset analysis of data from
      a prospective clinical trial that enrolled women undergoing surgery for an
      adnexal mass. Diagnostic performance of CA-125 and HE4 for epithelial ovarian
      cancer (EOC) detection in premenopausal women was determined. RESULTS: Of 229
      premenopausal patients, 195 (85%) had benign masses, 18 (8%) had EOC, and 16 (7%)
      had borderline ovarian tumor. The sensitivity of CA-125 and HE4 for EOC detection
      was 83.3% and 88.9%, respectively. The specificity of CA-125 and HE4 was 59.5%
      and 91.8%, respectively. A normal HE4 level ruled out invasive cancer in 98% of
      women with an elevated CA-125. CONCLUSION: HE4 offers superior specificity
      compared to CA-125 for the differentiation of benign and malignant adnexal masses
      in premenopausal women.

PMID- 21722870
TI  - Recurrence of placental dysfunction disorders across generations.
AB  - OBJECTIVE: Knowledge about the causes of placental dysfunction disorders is
      limited. We performed an intergenerational study, focusing on the risks of
      placental dysfunction disorders in mothers and fathers who had been born small
      for gestational age (SGA). STUDY DESIGN: Using linked generational data from the
      Swedish Medical Birth Register from 1973-2006, we identified 321,383 mother
      offspring units and 135,637 mother-father-offspring units. RESULTS: Compared with
      mothers who had not been born SGA, mothers who had been born SGA had the
      following adjusted odds ratios: late preeclampsia, 1.41 (95% confidence interval
      [CI], 1.26-1.57); early preeclampsia, 1.87 (95% CI, 1.38-2.35); placental
      abruption, 1.60 (95% CI, 1.23-2.09); spontaneous preterm birth, 1.11 (95% CI,
      1.00-1.23); and stillbirth, 1.24 (95% CI, 0.84-1.82). Compared with parents who
      had not been born SGA, the risk of preeclampsia was more than 3-fold increased if
      both parents had been born SGA, whereas if only the mother had been born SGA, the
      corresponding risk was increased by only 50%. CONCLUSION: There is an
      intergenerational recurrence of placental dysfunction disorders on the maternal
      side and most likely also on the paternal side.

PMID- 21722871
TI  - Patient Safety Series, a comment.

PMID- 21722872
TI  - Placental infarction identified by macroscopic examination and risk of cerebral
      palsy in infants at 35 weeks of gestational age and over.
AB  - OBJECTIVE: We sought to investigate whether placental infarction determined by
      macroscopic examination was associated with risk of cerebral palsy (CP). STUDY
      DESIGN: This was a population-based study of macroscopic placental infarcts in
      singletons>35 weeks' gestational age, in 158 perinatal deaths, 445 infants with
      CP, and 491 controls matched with CP cases for gestational age. RESULTS:
      Placental infarcts were recorded in 2.0% of controls, 4.4% of deaths (relative
      risk [RR], 2.2; 95% confidence interval [CI], 0.8-5.6]), 5.2% of infants with CP
      (P<.05, RR, 2.5; 95% CI, 1.2-5.3), and 8.4% with spastic quadriplegic CP
      (P=.0026; RR, 4.4; 95% CI, 1.8-10.6). In children with CP, unlike controls,
      placental infarction was associated with reduced fetal growth, older maternal
      age, more prior miscarriages, and poor neonatal condition, but not with maternal
      preeclampsia. CONCLUSION: Placental infarction identified by macroscopic
      examination was associated with increased risk of CP and the CP subtype, spastic
      quadriplegic CP. Antecedents of placental infarction differed in children with CP
      compared with control children.

PMID- 21722873
TI  - Multiple square sutures for postpartum hemorrhage: results and hysteroscopic
      assessment.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficiency and morbidity
      of multiple square sutures in severe postpartum hemorrhage. STUDY DESIGN: A
      retrospective study encompassed 30 multiple square sutures that were performed
      for severe postpartum hemorrhage in 26,605 deliveries in a tertiary maternity
      center. The main outcome measures were the ability to stop hemorrhage and the
      assessment of the uterine cavity by hysteroscopy at 3 months. RESULTS: Multiple
      square sutures stopped postpartum hemorrhage in 28 of 30 cases (93%). Twenty
      women underwent hysteroscopy after multiple square sutures. Eight women (40%) did
      not have intrauterine adhesions. Nine women (45%) had thin and localized
      intrauterine adhesions that were removed easily by the tip of the hysteroscope; 2
      women had moderate intrauterine adhesions that were resected. One patient had
      endometritis followed by severe intrauterine adhesions. CONCLUSION: Multiple
      square sutures are effective and safe for the control of severe postpartum
      hemorrhage and for uterine conservation in most cases. Although some patients had
      moderate or severe adhesions, a normal uterine cavity or minimal intrauterine
      adhesions that were removed easily were the most frequent findings at
      hysteroscopy. A prospective study may be helpful to compare the safety and
      efficiency of square and brace sutures.

PMID- 21722874
TI  - Effects of probiotics on experimental short-bowel syndrome.
AB  - BACKGROUND: This study was performed to analyze the potential benefits of
      probiotics on experimental short-bowel syndrome (SBS). METHODS: Forty-eight male
      Wistar-Albino rats were used in the study. The animals were divided into 6 groups
      as follows: control, rats that received probiotics, rats that underwent
      intestinal transection and anastomosis, rats that underwent anastomosis and
      received probiotics, rats that underwent 75% intestinal resection, and rats that
      underwent 75% intestinal resection plus received probiotics. Body weight
      monitoring, intestinal bowel diameter, villus length and crypt depth
      measurements, goblet cell count, mitosis, and immunohistochemical evaluation were
      used for the assessment of intestinal proliferation ability. RESULTS: Statistical
      analysis showed a significant difference in villus length, crypt depth, goblet
      cell count in villus and crypt, mitosis, and immunohistochemical evaluation in
      the jejunum when the SBS group was compared with the SBS group that received
      probiotics. There was no significant difference in these parameters in ileum.
      CONCLUSIONS: This trial clearly has shown that probiotics had a positive impact
      on jejunum in the experimental SBS.

PMID- 21722875
TI  - [Proactive bedside counseling of smokers hospitalized in cardiac intensive care
      unit].
AB  - AIM OF THE STUDY: To offer routine information on smoking cessation and bedside
      counseling to smokers admitted in cardiac intensive care unit. The objective is
      to encourage cessation and/or use of smoking cessation services after discharge.
      POPULATION AND METHODS: Thirty-three smokers were admitted in cardiac intensive
      care unit at the Georges Pompidou European hospital (HEGP) in Paris (France) from
      1st March to June 30th 2010. Assessment of tobacco use and offer of counseling
      and follow-up visits during and after hospital stay. Evaluation of tobacco use by
      telephone at least six months after discharge. RESULTS: It was found that 30.3%
      of the patients stopped smoking, mostly without specialized help despite heavy
      smoking prior to hospitalization. They declared being impressed by their hospital
      stay. Motives for smoking among continuing smokers were mostly automatic smoking
      and stress relief. They had declined any smoking aid, despite subsequent hospital
      stays in cardiac intensive care. Three smokers with a severe profile had died at
      follow-up. Smokers followed-up at HEGP were in need of nicotine replacement
      therapy. More than six months after hospital discharge, nearly all smokers
      remembered being offered bedside counseling to stop smoking. CONCLUSION: This
      experience reveals the importance of routine bedside counseling for smoking
      cessation in cardiac intensive care unit. Smokers in this unit often continue
      smoking even though smoking hinders cardiac rehabilitation.

PMID- 21722876
TI  - Relationships between subjective and objective measures in assessing postural
      stresses.
AB  - The purpose of this study is to investigate the relationships between subjective
      measures of discomfort and objective measures related to the assessment of
      postural stresses based on literature survey. Objective measures included posture
      holding time, maximum holding time (MHT), torque at joints, lifting index (LI)
      and compressive force (CF) at L5/S1. The major relationships identified in this
      literature survey were the following: 1) postural discomfort linearly increased
      with increasing holding time, and holding force, 2) whole body discomfort was
      inversely linearly proportional to the MHT, 3) body-part discomfort was related
      to objective measures such as torque at the relevant joint, 4) discomfort was
      strongly linearly related to LIs and CFs, and 5) the discomfort measured with the
      magnitude estimation was linearly related to that measured with Borg CR10. Thus,
      it is thought that discomfort might be used as a measure for quantifying postural
      stresses.

PMID- 21722877
TI  - Perivascular orientation of astrocytic plaques and tuft-shaped astrocytes.
AB  - Astrocytic plaques (APs) and tuft-shaped astrocytes (TAs) are frequently found in
      the brains of patients with corticobasal degeneration or progressive supranuclear
      palsy and are considered histopathological markers of these clinicopathological
      entities. Possible involvement of blood vessels in these lesions, occasionally
      found in routine histological examination, was estimated by observing thick
      sections (50-100 MUm). The relative distance between the center of each AP/TA to
      the nearest blood vessel was lesser than that between the nearest blood vessel
      and control random reference points, and this finding confirmed that APs/TAs are
      formed in close proximity to blood vessels. Furthermore, three-dimensional
      reconstruction of sections double-immunolabeled for phosphorylated tau (AT8) and
      blood vessels (von Willebrand factor) showed the smaller diameter of TAs (mean+/
      SD, 31.3+/-5.2 MUm; n=15) and closer contact of their AT8-positive processes to
      blood vessels, representing proximal accumulation of phosphorylated tau in TAs.
      This is in contrast with larger APs (88.5+/-15.2MUm, n=63), in which AT8-positive
      processes rarely have vascular contact. Even though the endfeet of astrocytes
      come into close contact with blood vessels, tau deposition, observed in both TAs
      and APs, was always oriented around the blood vessel, implying that these
      apparently distinct lesions (APs/TAs) share a common mechanism for tau deposition
      that is oriented around the blood vessel.

PMID- 21722878
TI  - Logic, language and the brain.
AB  - What is the role of language in human cognition? Within the domain of deductive
      reasoning, the issue has been the focus of numerous investigations without the
      emergence of a consensus view. Here we consider some of the reasons why
      neuroimaging studies of deductive reasoning have generated mixed results. We then
      review recent evidence suggesting that the role of language in deductive
      reasoning is confined to an initial stage in which verbally presented information
      is encoded as non-verbal representations. These representations are then
      manipulated by mental operations that are not based on the neural mechanisms of
      natural language. This article is part of a Special Issue entitled "The Cognitive
      Neuroscience".

PMID- 21722879
TI  - Enzymatic synthesis of novel branched sugar alcohols mediated by the
      transglycosylation reaction of pullulan-hydrolyzing amylase II (TVA II) cloned
      from Thermoactinomyces vulgaris R-47.
AB  - Transglycosylation reactions are useful for preserving a specific sugar structure
      during the synthesis of branched oligosaccharides. We have previously reported a
      panosyl unit transglycosylation reaction by pullulan-hydrolyzing amylase II (TVA
      II) cloned from Thermoactinomyces vulgaris R-47 (Tonozuka et al., Carbohydr.
      Res., 1994, 261, 157-162). The acceptor specificity of the TVA II
      transglycosylation reaction was investigated using pullulan as the donor and
      sugar alcohols as the acceptor. TVA II transferred the alpha-panosyl unit to the
      C-1 hydroxyl group of meso-erythritol, C-1 and C-2 of xylitol, and C-1 and C-6 of
      d-sorbitol. TVA II differentiated between the sugar alcohols' hydroxyl groups to
      produce five novel non-reducing branched oligosaccharides, 1-O-alpha
      panosylerythritol, 1-O-alpha-panosylxylitol, 2-O-alpha-panosylxylitol, 1-O-alpha
      panosylsorbitol, and 6-O-alpha-panosylsorbitol. The Trp(356)->Ala mutant showed
      similar transglycosylation reactions; however, panose production by the mutant
      was 4.0-4.5-fold higher than that of the wild type. This suggests that Trp(356)
      is important for recognizing both water and the acceptor molecules in the
      transglycosylation and the hydrolysis reaction.

PMID- 21722880
TI  - A novel amino-oligosaccharide isolated from the culture of Streptomyces strain
      PW638 is a potent inhibitor of alpha-amylase.
AB  - A novel amino-oligosaccharide, named SF638-1, was isolated from the culture
      filtrate of the Streptomyces strain PW638. Its chemical structure was determined
      by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and two
      dimensional nuclear magnetic resonance spectroscopy. The novel compound was a
      mixed inhibitor of human pancreatic alpha-amylase, with a K(i) value in the same
      order of magnitude as that of the alpha-amylase inhibitor, acarbose. SF638-1
      inhibited starch hydrolysis and glucose transfer in vitro, and suppressed
      postprandial blood glucose elevation in vivo. These results suggest that SF638-1
      may be a potent antidiabetic agent.

PMID- 21722881
TI  - Isolation and characterization of an immunoenhancing glucan from alkaline extract
      of an edible mushroom, Lentinus squarrosulus (Mont.) Singer.
AB  - A water-soluble glucan, isolated from the alkaline extract of the fruit bodies of
      an edible mushroom, Lentinus squarrosulus (Mont.) Singer was found to consist of
      (1->3,6)-linked, (1->3)-linked, (1->6)-linked, and terminal beta-d-glucopyranosyl
      moieties in a relative proportion of approximately 1:2:1:1. This polysaccharide
      showed optimum activation of macrophages as well as splenocytes and thymocytes at
      10MUg/mL. Structural investigation was carried out using sugar analysis,
      methylation analysis, periodate oxidation study, and NMR experiments ((1)H,
      (13)C, DEPT-135, DQF-COSY, TOCSY, NOESY, ROESY, HMQC, and HMBC). On the basis of
      above-mentioned experiments, the structure of the repeating unit of the
      polysaccharide was established as:

PMID- 21722882
TI  - [Enterovesical fistula caused by an indwelling bladder catheter].

PMID- 21722883
TI  - Post-mortem coronary CT angiography: a Leicester perspective.

PMID- 21722884
TI  - "Let's work together": what do infants understand about collaborative goals?
AB  - Collaboration is fundamental to our daily lives, yet little is known about how
      humans come to understand these activities. The present research was conducted to
      fill this void by using a novel visual habituation paradigm to investigate
      infants' understanding of the collaborative-goal structure of collaborative
      action. The findings of the three experiments reported here suggest that 14-month
      old infants understand that the actions of collaborative partners are
      complementary and critical to the attainment of a common collaborative goal.
      Importantly, 14-month-olds do not interpret the actions of two individuals in
      terms of a collaborative goal when their actions are not causally related. The
      implications of our findings for theories of collaboration and folk psychology
      are discussed.

PMID- 21722885
TI  - Robust prediction of protein subcellular localization combining PCA and WSVMs.
AB  - Automated prediction of protein subcellular localization is an important tool for
      genome annotation and drug discovery, and Support Vector Machines (SVMs) can
      effectively solve this problem in a supervised manner. However, the datasets
      obtained from real experiments are likely to contain outliers or noises, which
      can lead to poor generalization ability and classification accuracy. To explore
      this problem, we adopt strategies to lower the effect of outliers. First we
      design a method based on Weighted SVMs, different weights are assigned to
      different data points, so the training algorithm will learn the decision boundary
      according to the relative importance of the data points. Second we analyse the
      influence of Principal Component Analysis (PCA) on WSVM classification, propose a
      hybrid classifier combining merits of both PCA and WSVM. After performing
      dimension reduction operations on the datasets, kernel-based possibilistic c
      means algorithm can generate more suitable weights for the training, as PCA
      transforms the data into a new coordinate system with largest variances affected
      greatly by the outliers. Experiments on benchmark datasets show promising
      results, which confirms the effectiveness of the proposed method in terms of
      prediction accuracy.

PMID- 21722886
TI  - Classification of benign and malignant masses based on Zernike moments.
AB  - In mammography diagnosis systems, high False Negative Rate (FNR) has always been
      a significant problem since a false negative answer may lead to a patient's
      death. This paper is directed towards the development of a novel Computer-aided
      Diagnosis (CADx) system for the diagnosis of breast masses. It aims at
      intensifying the performance of CADx algorithms as well as reducing the FNR by
      utilizing Zernike moments as descriptors of shape and margin characteristics. The
      input Regions of Interest (ROIs) are segmented manually and further subjected to
      a number of preprocessing stages. The outcomes of preprocessing stage are two
      processed images containing co-scaled translated masses. Besides, one of these
      images represents the shape characteristics of the mass, while the other
      describes the margin characteristics. Two groups of Zernike moments have been
      extracted from the preprocessed images and applied to the feature selection
      stage. Each group includes 32 moments with different orders and iterations.
      Considering the performance of the overall CADx system, the most effective
      moments have been chosen and applied to a Multi-layer Perceptron (MLP)
      classifier, employing both generic Back Propagation (BP) and Opposition-based
      Learning (OBL) algorithms. The Receiver Operational Characteristics (ROC) curve
      and the performance of resulting CADx systems are analyzed for each group of
      features. The designed systems yield Az=0.976, representing fair sensitivity, and
      Az=0.975 demonstrating fair specificity. The best achieved FNR and FPR are 0.0%
      and 5.5%, respectively.

PMID- 21722887
TI  - Automatic measurement of midline shift on deformed brains using multiresolution
      binary level set method and Hough transform.
AB  - Midline shift (MLS) is an important quantitative feature clinicians use to
      evaluate the severity of brain compression by various pathologies. The midline
      consists of many anatomical structures including the septum pellucidum (SP), a
      thin membrane between the frontal horns (FH) of the lateral ventricles. We
      proposed a procedure that can measure MLS by recognizing the SP within the given
      CT study. The FH region is selected from all ventricular regions by expert rules
      and the multiresolution binary level set method. The SP is recognized using Hough
      transform, weighted by repeated morphological erosion. Our system is tested on
      images from 80 patients admitted to the neurosurgical intensive care unit. The
      results are evaluated by human experts. The mean difference between automatic and
      manual MLS measurements is 0.23 +/- 0.52 mm. Our method is robust and can be
      applied in emergency and routine settings.

PMID- 21722888
TI  - Contribution of the right intraparietal sulcus to numerosity and length
      processing: an fMRI-guided TMS study.
AB  - The critical involvement of the left and right intraparietal sulci (IPS) in
      numerosity and length processing was tested with neuro-navigated repetitive
      transcranial magnetic stimulation (rTMS). Participants had to categorize linear
      arrays of dots as containing "few" or "many" dots, and filled rectangles as
      "short" or "long". The stimulation sites were determined for each individual
      participant by identifying the IPS areas showing peak activity during a number
      comparison task in earlier functional magnetic resonance imaging (fMRI) studies.
      Compared to the stimulation of the vertex chosen as a control site, rTMS over the
      right IPS increased the error rate in both tasks. This result indicates that the
      integrity of the right IPS is a necessary condition not only for discriminating
      numerosities but also for performing accurate judgements of lengths. We propose
      that these two processes rely on a common representation and/or mechanism in the
      right IPS.

PMID- 21722889
TI  - Resetting our priorities in environmental health: an example from the South-North
      partnership in Lake Chapala, Mexico.
AB  - Lake Chapala is a major source of water for crop irrigation and subsistence
      fishing for a population of 300,000 people in central Mexico. Economic activities
      have created increasing pollution and pressure on the whole watershed resources.
      Previous reports of mercury concentrations detected in fish caught in Lake
      Chapala have raised concerns about health risks to local families who rely on
      fish for both their livelihood and traditional diet. Our own data has indicated
      that 27% of women of childbearing age have elevated hair mercury levels, and
      multivariable analysis indicated that frequent consumption of carp (i.e., once a
      week or more) was associated with significantly higher hair mercury
      concentrations. In this paper we describe a range of environmental health
      research projects. Our main priorities are to build the necessary capacities to
      identify sources of water pollution, enhance early detection of environmental
      hazardous exposures, and deliver feasible health protection measures targeting
      children and pregnant women. Our projects are led by the Children's Environmental
      Health Specialty Unit nested in the University of Guadalajara, in collaboration
      with the Department of Environmental Health of Harvard School of Public Health
      and Department of Pediatrics of the New York School of Medicine. Our partnership
      focuses on translation of knowledge, building capacity, advocacy and
      accountability. Communication will be enhanced among women's advocacy coalitions
      and the Ministries of Environment and Health. We see this initiative as an
      important pilot program with potential to be strengthened and replicated
      regionally and internationally.

PMID- 21722890
TI  - Ovarian stimulation modulates steroid receptor expression and spheroid attachment
      in peri-implantation endometria: studies on natural and stimulated cycles.
AB  - OBJECTIVE: To compare the effect of high serum E(2) levels on endometrial steroid
      receptors in gonadotropin-stimulated cycles (hCG + 7) and natural cycles (LH +
      7), and to study its effect on spheroid attachment. DESIGN: Observational.
      SETTING: University hospital. PATIENT(S): Infertile patient with normal menstrual
      cycles undergoing IVF treatment. INTERVENTION(S): Gonadotropin stimulation and
      endometrial biopsy; trophoblast spheroid (embryo surrogate, Jeg-3)-endometrial
      cell (Ishikawa) coculture assay. MAIN OUTCOME MEASURE(S): Steroid receptor
      expression by quantitative polymerase chain reaction and immunohistochemistry;
      spheroid attachment rate. RESULT(S): Endometrial biopsies from natural (n = 12)
      and stimulated (n = 23) cycles were obtained. The expression of estrogen receptor
      alpha (ERalpha) but not ERbeta or progesterone receptor (PR) transcript was
      significantly reduced in stimulated cycles compared with natural cycles.
      Glucocorticoid receptor (GR) transcript was significantly increased in the
      excessive responders of the stimulated cycle. There was no difference in ERalpha
      immunoreactivity in endometrial stroma, but a higher immunoreactivity was seen in
      endometrial glands of stimulated cycles. The endometrium of stimulated cycles had
      a lower expression of PR protein in glands, but a higher expression in stroma.
      Although no GR protein was detected in glands, GR protein expression was
      significantly up-regulated in stroma of the stimulated cycles. Endometrial cells
      treated with high steroid concentrations had a reduced spheroid attachment rate
      compared with the controls. CONCLUSION(S): High serum E(2) level affects the
      expression of steroid receptors in the endometrial cells and suppresses spheroid
      attachment.

PMID- 21722891
TI  - Egg freezing for age-related fertility decline: preventive medicine or a further
      medicalization of reproduction? Analyzing the new Israeli policy.
AB  - In December 2009, the Israel National Bioethics Council (INBC) issued
      recommendations permitting egg freezing to prevent both disease- and age-related
      fertility decline. The INBC report forms the basis of Israel's new policy
      regarding egg freezing. This article analyzes the medical section of the INBC's
      recommendations, comparing it with guidelines formulated by medical regulatory
      bodies in Europe and the United States. Our findings suggest that the INBC's
      recommendations consider age-related fertility decline to be a medical problem,
      and hence treat the new technology favorably, as preventive medicine, which we
      perceive as another instance of medicalization. The technology's risks are
      downplayed by the INBC, unlike the positions of medical organizations in both
      Europe and the United States, which consider the new technology experimental.
      This may culminate in raising false hopes about women's possible late genetic
      motherhood leading to involuntary future childlessness.

PMID- 21722893
TI  - Pituitary-adrenal and sympathetic nervous system responses to psychiatric
      disorders in women undergoing in vitro fertilization treatment.
AB  - OBJECTIVE: To evaluate whether psychological variables as well as changes in
      hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) at
      baseline and in response to a psychosocial stressor affect the chance of
      achieving pregnancy in women undergoing a first in vitro fertilization (IVF)
      cycle. DESIGN: Prospective study. SETTING: Private IVF center. PATIENT(S): 264
      women undergoing IVF or intracytoplasmic sperm injection (ICSI) treatment.
      INTERVENTION(S): Oocyte retrieval after ovarian stimulation. MAIN OUTCOME
      MEASURE(S): Standardized psychological questionnaires to assess anxiety and
      depression, and norepinephrine and cortisol in serum or follicular fluid measured
      by specific assays. RESULT(S): Only a trend increase was found in psychological
      scores during treatment, which did not affect the ongoing pregnancy rates. On the
      oocyte retrieval day, a statistically significant increase in norepinephrine and
      cortisol concentrations was found. Lower concentrations of norepinephrine and
      cortisol, both in serum and follicular fluid, were found in women whose
      treatments were successful. Concentrations of steroid in serum before treatment
      and in follicular fluid were positively associated with the State Anxiety scores.
      CONCLUSION(S): Norepinephrine and cortisol concentrations may negatively
      influence the clinical pregnancy rate in IVF treatment. These biological stress
      markers could be one of the links in the complex relationship between
      psychosocial stress and outcome after IVF-ICSI.

PMID- 21722892
TI  - Human immunodeficiency virus/acquired immunodeficiency syndrome and infertility:
      emerging problems in the era of highly active antiretrovirals.
AB  - OBJECTIVE: To review the effects of human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) in terms of its associated comorbid
      conditions and the side effects of antiretroviral treatment on fertility. DESIGN:
      PubMed computer search to identify relevant articles. SETTING: Research
      institution. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      None. RESULT(S): Biological alterations in reproductive physiology may account
      for subfertility in patients infected with HIV. Psychosocial factors in patients
      with HIV infection may affect their reproductive desires and outcomes.
      Antiretroviral medications may have direct toxicity on gametes and embryos.
      Available evidence indicates that fertility treatments can be a safe option for
      couples with HIV-discordant infection status, although the potential risk of
      viral transmission cannot be completely eliminated. CONCLUSION(S): Because their
      potential reproductive desires are increasingly becoming a concern in the health
      care of young HIV-infected patients, additional data are needed to address the
      effect of HIV and its treatments on their fertility and reproductive outcomes.

PMID- 21722894
TI  - The reproductive and metabolic effect of rosiglitazone on Chinese women with
      polycystic ovarian syndrome--a double-blind randomized placebo-controlled study.
AB  - OBJECTIVE: To investigate whether an insulin sensitizer has any effect on
      amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with
      polycystic ovarian syndrome (PCOS). DESIGN: Randomized controlled double-blind
      trial. SETTING: A tertiary referral center, Hong Kong. PATIENT(S): Chinese women
      who fulfilled the Rotterdam criteria of PCOS (n = 70). INTERVENTION(S):
      Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11
      months. MAIN OUTCOME MEASURE(S): Menstrual status as well as clinical and
      biochemical hyperandrogenism. RESULT(S): There is a significantly higher rate of
      regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6
      months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6
      [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores
      as well as serum T levels in both arms. CONCLUSION(S): We found a possible
      benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in
      our Chinese population. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-09000670
      (Chinese Clinical Trial Registry).

PMID- 21722895
TI  - Up-regulation of p21-activated kinase 1 by in vitro treatment with interleukin 1
      beta and its increased expression in ovarian endometriotic cysts.
AB  - We evaluated whether the proinflammatory cytokines can regulate p21-activated
      kinase (Pak1) expression in endometrial cells as well as whether its expression
      is increased in endometriotic cysts. We found that interleukin-1beta up-regulates
      Pak1 expression in endometrial stromal cells (ESC) and that the immunoreactivity
      of Pak1 is increased in the endometriotic cysts.

PMID- 21722896
TI  - Conjoined twins after intracytoplasmic sperm injection and transfer of day-3
      embryos.
AB  - OBJECTIVE: To report a case of conjoined twins conceived through assisted
      reproduction after intracytoplasmic sperm injection (ICSI) and the transfer of
      three eight-cell embryos on day 3. DESIGN: Case report. SETTING: Assisted
      reproduction unit of a private hospital. PATIENT(S): A 32-year-old patient
      underwent ICSI and received three embryos. INTERVENTION(S): Ovarian stimulation
      and ICSI. MAIN OUTCOME MEASURE(S): Images of the embryos and ultrasound images of
      the fetuses. RESULT(S): One embryo measuring 7 weeks, relatively big in size and
      bizarre in appearance with one heartbeat, was detected on transvaginal ultrasound
      at 6 weeks, 4 days of pregnancy. Two weeks later, another ultrasound was
      performed; two fetuses with a common heart were observed. In 10th week of
      pregnancy, two fetuses with two hearts and an attached thorax were observed. A
      diagnosis of thoracopagus was made, and the pregnancy was terminated.
      CONCLUSION(S): Conjoined twins conceived through assisted reproduction are
      extremely rare. This case, which occurred after transfer of cleavage-stage
      embryos, suggests that ovulation induction, ICSI, and assisted hatching may also
      play roles in addition to other factors commonly proposed to be responsible for
      conjoined twining, such as in vitro culture condition, culture time, and
      blastocyst-stage transfer.

PMID- 21722897
TI  - Pulmonary emboli after blunt trauma: timing, clinical characteristics and natural
      history.
AB  - BACKGROUND: Venous thromboembolism (VTE) frequently complicates the recovery of
      trauma patients, and contributes to morbidity and mortality. Recent studies
      showed an increase in diagnosis of pulmonary embolism (PE) mainly in the early or
      immediate period after trauma. The clinical significance of those incidental PEs
      is unclear. METHODS: The study cohort included all blunt trauma patients who had
      a contrast-enhanced CT of the chest performed as part of their initial trauma
      assessment from January 1, 2005 to January 31, 2007 in a large academic Canadian
      trauma centre. Patients diagnosed with PE at any point during admission were
      identified using our institutional trauma registry. All chest CT scans and
      electronic charts were reviewed. Patients were classified according to time of PE
      detection (immediate, early or late) and symptoms (asymptomatic or symptomatic).
      The clinical characteristics and hospital course of the patients who were
      diagnosed with immediate PE were described. RESULTS: 1259 blunt trauma patients
      were reviewed. Six patients presented with immediate PE (0.5%); nine patients
      were found to have early PE (0.7%) and 13 had late PE (1.0%). All six of the
      patients with immediate PE were classified as asymptomatic. Five of the nine
      patients with early PE were symptomatic and all 13 patients who developed late PE
      were symptomatic. Amongst the six patients with immediate PE, five survived 24h
      hospitalisation. Four of them were managed with prophylactic low molecular weight
      heparin and no other thromboembolic events were observed during admission or
      after discharge. CONCLUSIONS: The increased use of advanced CT technology in
      trauma patients has resulted in an increased diagnosis of incidental PEs that are
      asymptomatic. The clinical significance and management of these small, incidental
      PE are uncertain and further studies are needed to clarify the natural history of
      this controversial finding.

PMID- 21722898
TI  - Vitamin E therapy results in a reduction in HDL function in individuals with
      diabetes and the haptoglobin 2-1 genotype.
AB  - OBJECTIVE: Vitamin E provides cardiovascular protection to individuals with
      diabetes and the haptoglobin 2-2 genotype but appears to increase cardiovascular
      risk in individuals with diabetes and the haptoglobin 2-1 genotype. We have
      previously demonstrated that the haptoglobin protein is associated with HDL and
      that HDL function and its oxidative modification are haptoglobin genotype
      dependent. We set out to test the hypothesis that the pharmacogenetic interaction
      between the haptoglobin genotype on cardiovascular risk might be secondary to a
      parallel interaction between the haptoglobin genotype and vitamin E on HDL
      function. RESEARCH DESIGN AND METHODS: Fifty-nine individuals with diabetes and
      the haptoglobin 2-1 or 2-2 genotypes were studied in a double-blind placebo
      controlled crossover design. Participants were treated with either vitamin E
      (400IU) or placebo for 3 months and crossed over for an equivalent duration.
      Serum was collected at baseline and after the completion of each treatment. HDL
      functionality as well as HDL associated markers of oxidation and inflammation
      were measured after each interval in HDL purified from the cohort. RESULTS:
      Compared to placebo, vitamin E significantly increased HDL function in
      haptoglobin 2-2 but significantly decreased HDL function in haptoglobin 2-1. This
      pharmacogenetic interaction was paralleled by similar non-significant trends in
      HDL associated lipid peroxides, glutathione peroxidase, and inflammatory cargo.
      CONCLUSION: There exists a pharmacogenetic interaction between the haptoglobin
      genotype and vitamin E on HDL function (clinicaltrials.gov NCT01113671).

PMID- 21722899
TI  - A polymorphism in the ABCG1 promoter is functionally associated with coronary
      artery disease in a Chinese Han population.
AB  - OBJECTIVE: In this study, we examine the association of single nucleotide
      polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1)
      gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han
      population. METHODS: 1021 patients with CAD and 1013 unaffected control subjects
      were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to
      genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the
      promoter region and one (rs1044317) in the 3'-untranslated region (UTR). RESULTS:
      The human ABCG1 -367G>A polymorphism (rs57137919) showed a significantly
      decreased risk for CAD and myocardial infarction (MI) in a dominant model
      (adjusted OR = 0.73, p = 0.033 for CAD, and adjusted OR = 0.65, p = 0.014 for MI,
      respectively). The rs57137919 also showed an association with angiographic
      severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR = 0.40, p =
      0.005). The findings were further supported by luciferase reporter assay, in
      which the polymorphism impaired reporter gene expression. The ABCG1 -768G>A
      polymorphism (rs2234714) showed an association with CAD in a recessive model
      (adjusted OR = 0.64, p = 0.015), but did not demonstrate a functional influence
      on reporter gene expression in the luciferase reporter assay. CONCLUSIONS: The
      SNP rs57137919 in the ABCG1 promoter region is functionally associated with a
      reduced risk of CAD in a Chinese Han population.

PMID- 21722900
TI  - Cardiovascular implications of HIV-induced dyslipidemia.
AB  - Cardiovascular disease (CVD) is currently the second most frequent cause of death
      (after cancer) among HIV-positive subjects. The clinical use of highly active
      antiretroviral therapy (HAART) has dramatically reduced mortality and morbidity
      in HIV-positive population, leading to prolonged and improved quality of life.
      However, as mortality and morbidity from AIDS-related conditions improve, CVD
      assumes increasing magnitude. It is estimated that by 2015 more than 50% of HIV
      positive patients will be older than 50 years. Since age is a major unmodifiable
      cardiovascular risk factor, the risk for CVD in this population will
      significantly and progressively increase in the near future. A large part of the
      risk for cardiovascular events appears to be a result of lipid abnormalities
      characterizing HIV-positive persons. This review focuses on HIV-associated lipid
      abnormalities and CVD. Lipid abnormalities may be related to either viral
      infection, HAART or both. Dyslipidemia characterizing HIV-infected patients has
      become a therapeutic target to reduce cardiovascular risk of HIV-treated
      patients. HAART-treated patients show an atherogenic lipid profile comprised of
      low HDL-cholesterol levels, hypertrigliceridemia and increased levels of small
      LDL particles. Current guidelines for the treatment of dyslipidemia and reducing
      cardiovascular risk in HIV-positive patients suggest that when lifestyle
      modifications (i.e., diet and exercise) and switching antiretroviral therapy are
      not enough, statins should be the first-line therapy for dyslipidemia. HDL
      raising interventions (niacin and fibrates) should be considered to raise HDL
      levels and lower triglyceride in HIV-infected patients. Implications of lipid
      related interventions in HIV-treated patients to avoid drug interactions and
      their adverse effects are also discussed.

PMID- 21722901
TI  - The new joint EAS/ESC guidelines for the management of dyslipidaemias.

PMID- 21722902
TI  - Mutational analysis of the LDL receptor and APOB genes in Mexican individuals
      with autosomal dominant hypercholesterolemia.
AB  - The goal of this project was to identify families with autosomal dominant
      hypercholesterolemia (ADH) to facilitate early detection and treatment and to
      provide genetic counselling as well as to approximate the mutational diversity of
      ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases
      with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five
      mutations (24 LDLR, 1 APOB) were identified in 38 index cases. A total of 162
      individuals with ADH were identified using familial segregation analysis
      performed in 269 relatives of the index cases. In addition, a novel PCSK9
      mutation, c.1850 C>A (p.Ala617Asp), was detected. The LDLR mutations showed the
      following characteristics: (1) four mutations are novel: c.695 -1G>T,
      c.1034_1035insA, c.1586 G>A, c.2264_2273del; (2) the most common mutations were
      c.682 G>A (FH-Mexico), c.1055 G>A (FH-Mexico 2), and c.1090 T>C (FH-Mexico 3);
      (3) five mutations were identified in 3 or more apparently unrelated probands;
      (4) three mutations were observed in a true homozygous state; and (5) four index
      cases were compound heterozygous, and one was a carrier of two mutations in the
      same allele. These results suggest that, in Mexico, ADH exhibits allelic
      heterogeneity with 5 relatively common LDLR mutations and that mutations in the
      APOB gene are not a common cause of ADH. This knowledge is important for the
      genotype-phenotype correlation and for optimising both cholesterol lowering
      therapies and mutational analysis protocols. In addition, these data contribute
      to the understanding of the molecular basis of ADH in Mexico.

PMID- 21722903
TI  - Lipopolysaccharide-binding protein (LBP) is associated with total and
      cardiovascular mortality in individuals with or without stable coronary artery
      disease--results from the Ludwigshafen Risk and Cardiovascular Health Study
      (LURIC).
AB  - BACKGROUND: Atherosclerosis of coronary arteries is hallmarked by non-specific
      local inflammatory processes accompanied by a systemic response.
      Lipopolysaccharide-binding protein (LBP) has been suggested to be associated with
      coronary artery disease (CAD) in a previous study without follow-up. PATIENTS AND
      METHODS: LBP plasma levels were measured in 2959 participants of the Ludwigshafen
      Risk and Cardiovascular Health (LURIC) cohort study referred to coronary
      angiography at baseline between 1997 and 2000. Median follow-up time was 8.0
      years. Primary and secondary end points were cardiovascular and all-cause
      mortality, respectively. Multivariable adjusted logistic regression analyses were
      conducted to investigate the role of LBP. RESULTS: Serum LBP concentration was
      significantly increased in 2298 patients with angiographically confirmed CAD
      compared to 661 individuals without coronary atherosclerosis (6.78 MUg/mL (5.46
      8.84) vs. 6.13 MUg/mL (5.05-7.74), respectively; p<0.001). Moreover in
      multivariable logistic regression analyses, adjusted for established
      cardiovascular risk factors and markers of systemic inflammation, LBP was a
      significant and independent predictor of total and cardiovascular mortality
      (hazard ratio (HR) for all cause mortality: 1.43, 95% CI: 1.06-1.94, p=0.024; HR
      for cardiovascular mortality in the 4th quartile of LBP: 1.55, 95% CI: 1.06-2.27,
      p=0.025). CONCLUSION: The present results add information on LBP in CAD. The data
      underscore the potential importance of innate immune mechanisms for
      atherosclerosis. Further studies are needed to clarify the pathways between
      innate immune system activation and atherosclerosis.

PMID- 21722904
TI  - Tumor necrosis factor-alpha converting enzyme is a key mediator of abdominal
      aortic aneurysm development.
AB  - OBJECTIVE: Tumor necrosis factor (TNF)-alpha is known to be elevated in plasma
      and the aorta in abdominal aortic aneurysm (AAA) patients. We sought to clarify
      the role of TNF-alpha converting enzyme (Tace), which cleaves the transmembrane
      precursor of TNF-alpha, in AAA development. METHODS: We obtained aortic sample of
      AAA during surgical operation to assess the histological features and protein
      expression of human AAA. AAA was induced in mice with temporal systemic deletion
      of Tace by the inducible Mx-1 Cre transgene (TaceMx1) and in wild-type
      littermates (CON) by periaortic application of CaCl(2) (AAA/TaceMx1, AAA/CON).
      RESULTS: Tace expression was increased in human AAA samples as compared with
      normal aorta. Six weeks postoperatively, aortic diameter in AAA/TaceMx1 was
      decreased than in AAA/CON in association with attenuated TNF-alpha expression and
      extracellular matrix disruption. Increased activities of matrix metalloproteinase
      (MMP)-9 and MMP-2, numbers of Mac-2-positive macrophages, CD3-positive T
      lymphocytes and CD31-positive vessels in periaortic tissues, mRNA expression of
      CD68, monocyte chemotactic protein-1, TNF-alpha, vascular endothelial growth
      factor-A, p47 and glutathione peroxidases, and protein expression of phospho-c
      Jun N-terminal kinase in AAA were all attenuated by Tace deletion. Protein
      expression of transforming growth factor (TGF)-beta1 was upregulated by Tace
      deletion in sham-operated mice. TGF-beta1 expression was further increased in
      AAA/TaceMx1. CONCLUSIONS: Tace was overexpressed in the aortic wall in human and
      experimental AAA. Temporal systemic deletion of Tace prevented AAA development in
      association with attenuating inflammation, oxidative stress, neoangiogenesis and
      extracellular matrix disruption, suggesting a crucial role of Tace in AAA
      development.

PMID- 21722905
TI  - Fluid-structure interaction based study on the physiological factors affecting
      the behaviors of stented and non-stented thoracic aortic aneurysms.
AB  - Endovascular aneurysm repair (EVAR) is considered as a promising alternative
      technique for the treatment of aortic aneurysm. However, complications often
      occur after EVAR. In this paper, the influence of the physiological factors on
      the biomechanical behaviors of stented and non-stented thoracic aortic aneurysm
      (TAA) were presented. Representative TAA models with different intraluminal
      thrombus (ILT) volume before and after stent-graft (SG) implantation were built.
      Fluid-structure interaction effect was taken into account. The relative sliding
      between the SG wall and the aortic wall was allowed. Results showed that the
      cardiac cycle and ILT volume should be given much more consideration than
      previously thought in future investigations on TAA compliance. The time-averaged
      longitudinal displacement of SG necks were not uniformly distributed along
      circumferential direction of the aortic wall. Drag force increased with the
      increase of the cardiac cycle and decreased with the decrease of ILT volume.
      Computational results of TAA wall stress, sac and lumen pressure indicated that
      patient with faster heart rate might be at great risk of aneurysm rupture. The
      stress absorption effect of the SG was influenced by both ILT and cardiac cycle,
      which was also found to have strong impact on flow pattern. We believe that this
      study will bring new insights into further researches on the relevant issues and
      provide mechanics-based implications for clinical management of EVAR for TAA
      patient.

PMID- 21722906
TI  - The human proximal femur behaves linearly elastic up to failure under
      physiological loading conditions.
AB  - It has not been demonstrated whether the human proximal femur behaves linearly
      elastic when loaded to failure. In the present study we tested to failure 12
      cadaveric femurs. Strain was measured (at 5000Hz) on the bone surface with
      triaxial strain gages (up to 18 on each femur). High-speed videos (up to
      18,000frames/s) were taken during the destructive test. To assess the effect of
      tissue preservation, both fresh-frozen and formalin-fixed specimens were tested.
      Tests were carried out at two strain-rates covering the physiological range
      experienced during daily motor tasks. All specimens were broken in only two
      pieces, with a single fracture surface. The high-speed videos showed that failure
      occurred as a single abrupt event in less than 0.25ms. In all specimens, fracture
      started on the lateral side of the neck (tensile stress). The fractured specimens
      did not show any sign of permanent deformation. The force-displacement curves
      were highly linear (R(2)>0.98) up to 99% of the fracture force. When the last 1%
      of the force-displacement curve was included, linearity slightly decreased
      (minimum R(2)=0.96). Similarly, all force-strain curves were highly linear
      (R(2)>0.98 up to 99% of the fracture force). The slope of the first part of the
      force-displacement curve (up to 70% fracture force) differed from the last part
      of the curve (from 70% to 100% of the fracture force) by less than 17%. Such a
      difference was comparable to the fluctuations observed between different parts of
      the curve. Therefore, it can be concluded that the proximal femur has a linear
      elastic behavior up to fracture, for physiological strain-rates.

PMID- 21722907
TI  - Stretch along the craniocaudal axis improves shape recoverability of the spinal
      cord.
AB  - The spinal cord is physiologically stretched along the craniocaudal axis, and is
      subjected to tensile stress. The purpose of this study was to examine the effect
      of the tensile stress on morphological plasticity of the spinal cord under
      compression and decompression condition. The C1-T2 spinal column was excised from
      4 rabbits. The laminae and lateral masses were removed. After excision of
      surrounding structures, a small rod was placed on the spinal cord. The rod was
      connected with a pan of the scale balance. Varying the weight between 0 and 20g
      on the other scalepan, the indentation of the rod was measured. Then, the spinal
      cord was cut transversely to remove longitudinal tensile stress. The samples were
      measured again with the same protocol at point 10mm caudal to each pre-measured
      point on the spinal cord. The shape recovery rate was calculated. The length of
      the spinal cord decreased by 9.7% after the separation. The maximum indentation
      was 2.1mm (mean) at 20g, and did not differ between the separated and un
      separated cords. The recovery rate was not significantly different between the
      separated and un-separated cords until 3g. At the load under 3g, the recovery
      rate after the separation was significantly lower than that before the
      separation. The tensile stress along the craniocaudal axis in the spinal cord did
      not affect the spinal cord deformation in response to the compression, but it did
      affect the shape recoverability after the decompression.

PMID- 21722908
TI  - The Valencian celebration of the International Symposium on Chromatography (ISC
      2010).

PMID- 21722909
TI  - Comparing columns for gas chromatography with the two-parameter model for
      retention prediction.
AB  - The retention times of selected compounds in temperature programmed gas
      chromatography were predicted using a two-parameter model, on the basis of
      thermodynamic data obtained from isothermal runs on seven capillary columns,
      primarily substituted with 5% diphenylsiloxane. The scope for using thermodynamic
      data obtained from isothermal runs on one column to optimize separation on a
      different column or a different instrument setup was investigated. Additionally,
      the predictive utility of thermodynamic data obtained using a DB-5 column that
      had been in use for three years was compared to that of a new column of the same
      model. It was found that satisfactory separation could be achieved on one
      capillary column or instrument setup on the basis of thermodynamic data obtained
      using a different column or instrument set-up.

PMID- 21722910
TI  - Direct and simultaneous determination of representative byproducts in a
      lignocellulosic hydrolysate of corn stover via gas chromatography-mass
      spectrometry with a Deans switch.
AB  - Pretreatment is one of the most important steps in producing fuel ethanol from
      lignocellulosic biomass. Simple, fast and accurate quantification of byproducts
      in lignocellulosic hydrolysates is critical to optimize the pretreatment
      procedures, but still a challenge. In this paper, a new GC-MS (SIM) method based
      on a Deans switch has been developed for the determination of byproducts in a
      corn stover hydrolysate. The Deans switch was incorporated into a hardware system
      that facilitated the direct aqueous injection (DAI) on GC-MS system. Simultaneous
      chromatographic separation and quantification of 18 byproducts including four
      aliphatic acids, five furan derivatives, four phenolic compounds and five others
      were achieved within 45 min. The detection limits of the presented method for
      various byproducts were in the range of 0.007-0.832 mg/L. The within-day and
      between-day precisions of the method were less than 6.0% (RSD, n=6). The accuracy
      of the method was confirmed with recoveries of 86-128%. A lignocellulosic
      hydrolysate sample of corn stover was successfully analyzed using this method,
      with aliphatic acids and furan derivatives accounting for 89.15% of the selected
      total byproducts.

PMID- 21722911
TI  - A facile method of synthesis of asymmetric hollow silica spheres.
AB  - This paper presents a "one-step" method to synthesize asymmetric hollow silica
      spheres. In this method, when positively charged polystyrene particles were
      blended with mercaptopropyltriethoxysilane and stirred at 50  degrees C in
      alkaline ethanol/water medium for a period of time, Janus or lobed asymmetric
      hollow silica spheres could be directly obtained, just changing the ratio of
      ethanol to water in the reaction medium. Transmission electron microscopy (TEM)
      and scanning electron microscopy (SEM) were used to characterize the morphology
      and topography of the asymmetric hollow silica spheres. The formation mechanism
      was described in detail.

PMID- 21722912
TI  - Capillary rise of superspreaders.
AB  - Trisiloxane surfactants, known as 'superspreaders', are commonly employed in
      numerous applications where enhanced wetting is of the utmost importance. The
      underlying mechanisms of superspreader wetting have been a focus of scientific
      interest for ca. 2 decades, and a number of mechanisms have been proposed to
      explain the unique trisiloxane dynamics. We have studied trisiloxane behaviour in
      thin capillaries to get further insight into their interfacial activity.
      Additionally, our knowledge of the capillary rise of superspreaders is
      surprisingly limited, and the effect of this extraordinary group of surfactants
      on capillary phenomena has been largely overlooked. Diffusion was confirmed to be
      the limiting factor of trisiloxane behaviour. A tentative theoretical explanation
      for the phenomenon studied and an appropriate mathematical model are presented.
      It is concluded that the enhancement of wetting due to surfactant addition is
      also a function of geometry: the effect is clear for a sessile drop, but more
      complex and less beneficial in a capillary.

PMID- 21722913
TI  - Fibrinogen stability under surfactant interaction.
AB  - Differential scanning calorimetry (DSC), circular dichroism (CD), difference
      spectroscopy (UV-vis), Raman spectroscopy, and small-angle X-ray scattering
      (SAXS) measurements have been performed in the present work to provide a
      quantitatively comprehensive physicochemical description of the complexation
      between bovine fibrinogen and the sodium perfluorooctanoate, sodium octanoate,
      and sodium dodecanoate in glycine buffer (pH 8.5). It has been found that sodium
      octanoate and dodecanoate act as fibrinogen destabilizer. Meanwhile, sodium
      perfluorooctanoate acts as a structure stabilizer at low molar concentration and
      as a destabilizer at high molar concentration. Fibrinogen's secondary structure
      is affected by all three studied surfactants (decrease in alpha-helix and an
      increase in beta-sheet content) to a different extent. DSC and UV-vis revealed
      the existence of intermediate states in the thermal unfolding process of
      fibrinogen. In addition, SAXS data analysis showed that pure fibrinogen adopts a
      paired-dimer structure in solution. Such a structure is unaltered by sodium
      octanoate and perfluoroctanoate. However, interaction of sodium dodecanoate with
      the fibrinogen affects the protein conformation leading to a complex formation.
      Taken together, all results evidence that both surfactant hydrophobicity and tail
      length mediate the fibrinogen stability upon interaction.

PMID- 21722914
TI  - Coronary artery dilation in sickle cell disease.
AB  - OBJECTIVE: To evaluate the prevalence of coronary artery dilation in children
      with sickle cell disease (SCD). STUDY DESIGN: This is a retrospective analysis
      performed in patients, between 10 and 19 years old, with SCD who underwent a
      routine transthoracic echocardiographic evaluation over a 20-month period. The
      left main, left anterior descending, and proximal right coronary artery
      diameters, as well as clinical and laboratory variables and other
      echocardiographic results were collected. Echocardiographic measurements were
      converted to z scores by using information from a large control population of
      normal children. Coronary artery ectasia (CAE) was defined as a coronary artery
      diameter z score >= 2. The patients with CAE were compared with those without CAE
      by using univariate and multivariate analyses. RESULTS: Seventeen of 96 patients
      with SCD (17.7%) had CAE. There were no differences in sex, age, height, weight,
      body surface area, or genotype between those with and those without CAE. Patients
      with CAE had larger left ventricular end-diastolic dimension, shortening
      fraction, septal thickness, posterior wall thickness, mass, mass-to-volume ratio,
      and white blood cell count. Multivariate analysis revealed that the mass-to
      volume ratio and elevated white blood cell count were associated with CAE.
      CONCLUSION: CAE is common in SCD and is associated with left ventricular
      hypertrophy and inflammation.

PMID- 21722915
TI  - Using tele-education to train civilian physicians in an area of active conflict:
      certifying Iraqi physicians in Pediatric Advanced Life Support from the United
      States.
AB  - Years of violence have resulted in a lack of trained health care providers in
      Iraq. To address this need, International Medical Corps has implemented a
      national emergency care program for the country. As part of this program, we
      implemented via tele-education the country's first civilian course in Pediatric
      Advanced Life Support.

PMID- 21722916
TI  - Endothelial function and carotid intima-medial thickness in adolescents with type
      2 diabetes mellitus.
AB  - OBJECTIVE: We assessed the effect of type 2 diabetes mellitus and obesity on flow
      mediated dilation (FMD) and endothelial-dependent vasodilation and carotid intima
      medial thickness (cIMT) in young people. STUDY DESIGN: Adolescents were recruited
      in 3 groups: subjects with type 2 diabetes mellitus (n = 15), subjects who were
      obese and non-insulin resistant (n = 13), and lean control subjects (n = 13).
      Body mass index was similar in subjects with obesity and subjects with type 2
      diabetes mellitus, but higher compared with that of lean control subjects (both P
      < .001). Brachial artery FMD and cIMT were assessed by using Duplex ultrasound
      scanning imaging. RESULTS: There were no significant differences in brachial or
      common carotid arterial diameters in the groups. cIMT was significantly greater
      in the group with type 2 diabetes mellitus (0.54 +/- 0.01mm) compared with both
      the lean control (0.46 +/- 0.02 mm, P < .001) and obese control (0.46 +/- 0.02
      mm, P < .01) groups. FMD was significantly decreased in the group with type 2
      diabetes mellitus (7.98% +/- 0.54%) compared with the lean group (10.40% +/-
      1.00%, P < .05). CONCLUSIONS: Measures of vascular health were impaired in
      adolescents with type 2 diabetes mellitus compared with lean and obese
      adolescents who were not insulin resistant. Measures of arterial function and
      structure may provide pre-clinical measures of cardiovascular disease in young
      people at elevated risk.

PMID- 21722917
TI  - Electronic measurement of medication adherence in pediatric chronic illness: a
      review of measures.

PMID- 21722918
TI  - Association of Crohn's disease, thiopurines, and primary epstein-barr virus
      infection with hemophagocytic lymphohistiocytosis.
AB  - OBJECTIVE: To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in
      a well-defined population of children with inflammatory bowel disease (IBD) and
      evaluate the common clinical and laboratory characteristics of individuals with
      IBD who developed HLH. STUDY DESIGN: We conducted a retrospective study of all
      children who developed HLH over an 8-year period. The incidence of HLH in
      patients with IBD was calculated using US census data and a statewide project
      examining the epidemiology of pediatric IBD. RESULTS: Among children in
      Wisconsin, 20 cases of HLH occurred during the study period; 5 cases occurred in
      children with IBD. Common characteristics include: Crohn's disease (CD),
      thiopurine administration, fever lasting more than 5 days, lymphadenopathy,
      splenomegaly, anemia, lymphopenia, and elevated serum triglycerides and ferritin.
      Of the patients, 4 had primary Epstein-Barr virus infections. The incidence of
      HLH among all children in Wisconsin was 1.5 per 100 000 per year. The risk was
      more than 100-fold greater for children with CD (P < .00001). CONCLUSIONS:
      Pediatric patients with CD are at increased risk for developing HLH; primary
      Epstein-Barr virus infection and thiopurine administration may be risk factors.

PMID- 21722919
TI  - P11 expression and PET in bipolar disorders.
AB  - BACKGROUND: Bipolar disorder (BD) is a common mental disorder, subdivided into BD
      I and BD-II. Currently, few biomarkers differentiate BD-I from BD-II. However, it
      is suggested that peripheral blood mononuclear cell (PBMC) mRNA levels of p11 and
      positron emission tomography (PET) might be potential biomarkers for BD. METHODS:
      Healthy controls (HCs), BD-I, and BD-II patients in remission (n = 20 in each
      group) underwent a resting PET study with the radiotracer [(18)F]-2-deoxy-2
      fluoro-d-glucose ((18)F-FDG). PBMC p11 mRNA levels were determined by
      quantitative real-time PCR. RESULTS: Comparing BD patients to HCs, normalized
      glucose metabolism (NGM) was higher in the hippocampus, parahippocampus, and
      amygdala, but lower in the anterior cingulate cortex (aCC), medial prefrontal
      cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), insula and thalamus.
      Compared to BD-II, BD-I had hypometabolism of glucose in the aCC, bilateral
      middle and inferior gyrus, insula and striatum, and hypermetabolism of glucose in
      the left parahippocampus. PBMC p11 mRNA was over-expressed in both BD-I and BD
      II, although there was no significant difference in its expression levels between
      BD-I and B-II patients. Further, there were significant positive correlations
      between PBMC p11 mRNA and NGM in the mPFC, aCC, left insula, bilateral
      orbitofrontal cortex (OFC), and left middle, inferior and superior temporal gyri.
      Also, PBMC p11 mRNA was positively correlated to the number of depressive
      episodes in BD patients, especially in BD-I patients. DISCUSSION: This study
      demonstrates that PBMC p11 mRNA expression is associated with neural activation
      in the brain of BD patients and warrants a larger translational study to
      determine its clinical utility.

PMID- 21722920
TI  - The impact of psychiatric illness on suicide: differences by diagnosis of
      disorders and by sex and age of subjects.
AB  - People with a psychiatric illness are at high risk for suicide; however,
      variation of the risk by patients' sex and age and by specific diagnosis needs to
      be explored in a more detail. This large population study systematically assesses
      suicide incidence rate ratio (IRR) and population attributable risk (PAR)
      associated with various psychiatric disorders by comparing 21,169 suicides in
      Denmark over a 17-year period with sex-age-time-matched population controls. The
      study shows that suicide risk is significantly increased for persons with a
      hospitalized psychiatric disorder and the associated risk varies significantly by
      diagnosis and by sex and age of subjects. Further adjustment for personal
      socioeconomic differences eliminates the IRRs associated with various disorders
      only to a limited extend. Recurrent depression and borderline personality
      disorder increase suicide risk the strongest while dementia increases the risk
      the least for both males and females. The influence of various disorders
      generally weakens with increasing age; however, there are important exceptions.
      Schizophrenia affects people aged <=35 years the strongest in terms of both IRR
      and PAR. Recurrent depression increases suicide risk particularly strong in all
      age groups and the associated PAR increases steadily with age. Borderline
      personality disorder has a strong effect in young people, especially those <=35
      years. Alcohol use disorder accounts the highest PAR of suicides in males of 36
      60 years old. For the elderly above 60 years old, reaction to stress and
      adjustment disorder increases the risk for suicide the most in both sexes. These
      findings suggest that approaches to psychiatric suicide prevention should be
      varied according to diagnosis and sex and age of subjects.

PMID- 21722921
TI  - NINJ2 polymorphism is associated with ischemic stroke in Chinese Han population.
AB  - Recently, a genome-wide association study reported an association between two
      single nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 near NINJ2 gene
      and ischemic stroke in Caucasians. Therefore, NINJ2 gene is an important
      candidate locus in the prevalence of ischemic stroke. We performed a hospital
      based genetic association study in Chinese Han subjects to investigate the
      relationship between NINJ2 gene and ischemic stroke. We genotyped 14 tagging
      single nucleotide polymorphisms (tSNP) in 749 ischemic stroke subjects and 924
      control subjects and conducted the association between these tSNPs and ischemic
      stroke. We detected a tSNP rs10849373 in the first intron of the NINJ2 gene
      significantly associated with ischemic stroke (both genotype and allelic
      p=0.0001). The minor A allele increased the risk of ischemic stroke with a per
      allele OR of 1.37 for the additive genetic model in univariate analysis
      (p=0.0001). The significance remained after adjustment for the covariates of age,
      gender, BMI, cigarette smoking, alcohol drinking, hypertension, and diabetes.
      Therefore, we report a new genetic variant, rs10849373, located in the first
      intron of the NINJ2 gene, conferring risk of ischemic stroke in Chinese Han
      subjects. Further genetic association and functional studies are required to
      search the causal functional variant in linkage disequilibrium with this
      polymorphism.

PMID- 21722922
TI  - Late-onset mental deterioration and fluctuating dystonia in a female patient with
      a truncating MECP2 mutation.
AB  - A 26-year-old woman with psychomotor developmental delay since late infancy
      showed rapid deterioration of her psychomotor abilities at the 11 years of age.
      She had gained the ability to verbally express herself and perform motor
      activities such as running and dancing in early childhood, but she lost the
      ability to verbally communicate and was unable to walk independently after this
      period. She also presented with dystonia in the right extremities, which markedly
      fluctuated with a periodicity of hours to months. Sleep disturbance and epileptic
      seizures also emerged during adolescence. Frontal lobe atrophy and hypoperfusion
      of the left cerebral hemisphere were noted on neuroimaging examinations. Analysis
      of the MECP2 gene revealed a late truncating mutation of c.1196_1200delCCACC
      (p.P399QfsX4) near the 3'-terminal of the coding region. The phenotype of this
      patient corresponds to the rare, unestablished variant of "late childhood
      deterioration" in MECP2-related disorders. For the first time, MECP2 mutation was
      confirmed to be the genetic basis of this condition.

PMID- 21722923
TI  - Immune responses to combined effect of hypoxia and high temperature in the green
      lipped mussel Perna viridis.
AB  - Flow cytometry was used to examine immune responses in haemocytes of the green
      lipped mussel Perna viridis under six combinations of oxygen level (1.5 mg O2 l(
      1), 6.0 mg O2 l(-1)) and temperature (20  degrees C, 25  degrees C and 30 
      degrees C) at 24 h, 48 h, 96 h and 168 h. The mussels were then transferred to
      normoxic condition (6.0 mg O2 l(-1)) at 20  degrees C for further 24 h to study
      their recovery from the combined hypoxic and temperature stress. Esterase (Est),
      reactive oxygen species (ROS), lysosome content (Lyso) and phagocytosis (Pha)
      were reduced at high temperatures, whereas hypoxia resulted in higher haemocyte
      mortality (HM) and reduced phagocytosis. For HM and Pha, changes were observed
      after being exposed to the stresses for 96 h, whereas only a 24 h period was
      required for ROS and Lyso, and a 48 h one for Est. Recovery from the stresses was
      observed for HM and Pha but not other immune responses.

PMID- 21722924
TI  - Richards Bay Harbour: metal exposure monitoring over the last 34 years.
AB  - Richards Bay Harbour is South Africa's premier bulk cargo port. It was
      constructed in the Mhlathuze estuary in 1976 and over the past 34 years has
      become South Africa's most modern and largest cargo handling port. Although no
      official monitoring programme is in progress various studies by different groups
      have provided relevant data with respect to changing metal levels in brown mussel
      tissue (Perna perna) over the last 34 years. Eleven elements were analysed in
      brown mussels from the main channel in Richards Bay Harbour using ICP-MS. The
      results indicate that the metal concentrations in the mussel tissue remained
      relatively constant between 1974 and 2005. The mean metal concentrations
      increased significantly in 2005 possibly due to the construction of the new coal
      terminal and associated dredging activities. Mean metal concentrations in the
      2008 sampling event were also elevated due to increased run off during an above
      average rainy season.

PMID- 21722925
TI  - Hydrocarbon composition and distribution in a coastal region under influence of
      oil production in northeast Brazil.
AB  - Waters and sediments from the Potiguar Basin (NE Brazilian coast) were
      investigated for the presence and nature of polycyclic aromatic hydrocarbons
      (PAH) and aliphatic hydrocarbons. The region receives treated produced waters
      through a submarine outfall system serving the industrial district. The total
      dispersed/dissolved concentrations in the water column ranged from 10-50 ng L(-1)
      for ?16PAH and 5-10 MUg L(-1) for total aliphatic hydrocarbons. In the sediments,
      hydrocarbon concentrations were low (0.5-10 ng g(-1)for ?16PAH and 0.01-5.0 MUg
      g(-1) for total aliphatic hydrocarbons) and were consistent with the low organic
      carbon content of the local sandy sediments. These data indicate little and/or
      absence of anthropogenic influence on hydrocarbon distribution in water and
      sediment. Therefore, the measured values may be taken as background values for
      the region and can be used as future reference following new developments of the
      petroleum industry in the Potiguar Basin.

PMID- 21722926
TI  - Why are hatching and emergence success low? Mercury and selenium concentrations
      in nesting leatherback sea turtles (Dermochelys coriacea) and their young in
      Florida.
AB  - Leatherback sea turtles (Dermochelys coriacea) have low hatching and emergence
      success compared to other sea turtle species. Postmortem examinations of
      hatchlings showed degeneration of heart and skeletal muscle that was similar to
      that found in other neonates with selenium deficient mothers. Selenium deficiency
      can result from elevated concentrations of bodily mercury. Ingested mercury is
      detoxified by the liver through mercury-selenium compound formation. In animals
      persistently exposed to mercury, the liver's ability to detoxify this element may
      decrease, especially if dietary selenium is insufficient. We measured mercury and
      selenium concentrations in nesting female leatherbacks and their hatchlings from
      Florida and compared the levels to hatching and emergence success. Both liver
      selenium and the liver selenium-to-mercury ratio positively correlated with
      leatherback hatching and emergence success. This study provides the first
      evidence for the roles of mercury and selenium in explaining low reproductive
      success in a globally imperiled species, the leatherback sea turtle.

PMID- 21722927
TI  - Coastal defence through low crested breakwater structures: jumping out of the
      frying pan into the fire?
AB  - The Adriatic coast of Punta Marina (Ravenna) is protected by 3-km long low
      crested breakwater structures (LCSs). Through a 3-years long multidisciplinar
      study, we assessed the impact of such defensive structures on environmental and
      biological condition. LCSs create pools where conditions are very different from
      the surrounding nearshore system. Mechanical disturbance by currents and waves
      varied greatly in intensity and frequency between seaward and landward sides of
      the structures. Sedimentary budget was positive at the landward side, but it was
      due to a gain on the seafloor and not on the emerged beach. The budget at seaward
      was negative. LCSs determine differences in benthic assemblages, alter the
      seasonal pattern of communities, and modify seasonal fluctuations of animal
      assemblages. Landward sheltered areas can be seen as "lagoonal island" surrounded
      by a "sea of marine habitat". Differences in ecological quality status, obtained
      through M-AMBI, are due to the sum of these factors.

PMID- 21722928
TI  - Going alone: the lived experience of female Arab-Muslim nursing students living
      and studying in the United States.
AB  - Since 2004, international student enrollment in the United States has increased.
      Middle Eastern students studying in the United States have been part of the
      increase. In 2008-2009 there were 29 140 Middle Eastern students, representing an
      18% increase from the previous academic year. Despite these increases, there is
      limited research examining the experience of Arab-Muslim international students
      or international nursing students studying in the United States. Phenomenological
      inquiry was used to describe the experience of 12 female Omani nurses living in
      the United States while studying for their baccalaureate degrees in nursing. The
      women described the experience of going alone and being away from the support and
      presence of their large, extended families; this influenced their international
      student experience. They also described their religious, cultural, and
      educational adaptation. The experience of living and studying nursing in the
      United States was transformational as they became self-reliant, learned their
      capabilities, and adapted to cultural and educational expectations.

PMID- 21722929
TI  - Is it possible to harness health equitably for men and women?

PMID- 21722930
TI  - Appraisal of the burden of genital warts from a healthcare and individual patient
      perspective.
AB  - OBJECTIVE: Worldwide, genital warts, caused by human papillomavirus (HPV) is a
      common, sexually transmitted disease. The overall disease management strategy for
      genital warts should be determined not only by the prevalence, but also by the
      impact of the disease on individuals and society. The purpose of this study was
      therefore to investigate the epidemiological, economic and quality of life (QoL)
      burden of genital warts. METHODS: A systematic literature review was conducted on
      the epidemiology, QoL and management cost of genital warts in the USA, UK and
      France, based on studies published between 1998 and 2008. Due to scarcity of
      data, all studies reporting standardized QoL assessments among patients with
      genital warts were utilized, regardless of country of origin. Original studies
      were preferred over information cited in review articles. RESULTS: Data from
      three countries suggest that genital warts occur in 0.06-0.23% of the population
      each year. Despite the fact that spontaneous remissions occur frequently (up to
      40%), patients often prefer immediate treatment. While treatment can be costly in
      absolute terms (?163-510 per treatment episode), these costs are lower compared
      with other sexually transmitted infections (STIs). Modest reductions in QoL have
      been noted, which may be mitigated through adequate patient education and
      support. CONCLUSIONS: While genital warts are an inconvenience for many patients,
      the occurrence may be lower than often quoted in the literature, and the economic
      burden on society is less than for other prominent STIs. However, concerted
      efforts to establish improved data collection and surveillance systems are needed
      in order to accurately define the burden of genital warts on individuals and
      society.

PMID- 21722932
TI  - Determination of nonlinear medium parameter B/A using model assisted variable
      length measurement approach.
AB  - This work addresses the difficulties in the measurements of the nonlinear medium
      parameter B/A and presents a modification of the finite amplitude method (FAM),
      one of the accepted procedures to determine this parameter. The modification is
      based on iterative, hybrid approach and entails the use of the versatile and
      comprehensive model to predict distortion of the pressure-time waveform and its
      subsequent comparison with the one experimentally determined. The measured p-t
      waveform contained at least 18 harmonics generated by 2.25 MHz, 29 mm effective
      diameter, single element, focused PZT source (f-number 3.5) and was recorded by
      Sonora membrane hydrophone calibrated in the frequency range 1-40 MHz. The
      hydrophone was positioned coaxially at the distal end of the specially designed,
      two-section assembly comprising of one, fixed length (60mm), water-filled
      cylindrical container and the second, variable length (60-120 mm) container that
      was filled with unknown medium. The details of the measurement chamber are
      described and the reasons for this specific design are analyzed. The data were
      collected with the variable length chamber filled with 1.3-butanediol, which was
      used as a close approximation of tissue mimicking phantom. The results obtained
      provide evidence that a novel combination of the FAM with the semi-empirical
      nonlinear propagation model based on the hyperbolic operator is capable of
      reducing the overall uncertainty of the B/A measurements as compared to those
      reported in the literature. The overall uncertainty of the method reported here
      was determined to be +/-2%, which enhances the confidence in the numerical values
      of B/A measured for different, clinically relevant media. Optimization of the
      approach is also discussed and it is shown that it involves an iterative
      procedure that entails a careful selection of the acoustic source and its
      geometry and the axial distance over which the measurements need to be performed.
      The optimization also depends critically on the experimental determination of the
      source surface pressure amplitude.

PMID- 21722933
TI  - In vitro evaluation of the impact of ultrasound scanner settings and contrast
      bolus volume on time-intensity curves.
AB  - The objective of this study was to assess in vitro the impact of ultrasound
      scanner settings and contrast bolus volume on time-intensity curves formed from
      dynamic contrast-enhanced ultrasound image loops. An indicator-dilution
      experiment was developed with an in vitro flow phantom setup used with SonoVue
      contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips
      iU22 scanner and two transducers (L9-3 linear and C5-1 curvilinear). The
      following ultrasound scanner settings were investigated, along with contrast
      bolus volume: contrast-specific nonlinear pulse sequence, gain, mechanical index,
      focal zone depth, acoustic pulse center frequency and bandwidth. Four parameters
      (rise time, mean transit time, peak intensity, and area under the curve) were
      derived from time-intensity curves which were obtained after pixel by pixel
      linearization of log-compressed data (also referred to as video data) included in
      a region of interest. Rise time was found to be the parameter least impacted by
      changes to ultrasound scanner settings and contrast bolus volume; the associated
      coefficient of variation varied between 0.7% and 6.9% while it varied between
      0.8% and 19%, 12% and 71%, and 9.2% and 66%, for mean transit time, peak
      intensity, and area under the curve, respectively. The present study assessed the
      impact of ultrasound scanner settings and contrast bolus volume on time-intensity
      curve analysis. One should be aware of these issues to standardize their
      technique in each specific organ of interest and to achieve accurate, sensitive,
      and reproducible data using dynamic contrast-enhanced ultrasound. One way to
      mitigate the impact of ultrasound scanner settings in longitudinal, multi-center
      quantitative dynamic contrast-enhanced ultrasound studies may be to prohibit any
      adjustments to those settings throughout a given study. Further clinical studies
      are warranted to confirm the reproducibility and diagnostic or prognostic value
      of time-intensity curve parameters measurements in a particular clinical scenario
      of interest, for example that of cancer patients undergoing vascular targeting
      therapies.

PMID- 21722934
TI  - Immunogenicity of low-pH treated whole viral influenza vaccine.
AB  - Low pH treatment of influenza virus hemagglutinin (HA) exposes its relatively
      conserved stalk domain, suggesting a potential immunogen with capability to
      induce broader immune responses. Here, we describe characterization,
      immunogenicity, antigenicity, and protective immunity induced by low pH treated
      inactivated whole viral vaccine in comparison with the untreated vaccine. The
      acidic pH treated viral vaccine showed high susceptibility to proteolytic
      cleavage and low hemagglutination activity indicating conformational changes.
      Immunization of mice with low pH treated viral vaccine induced lower levels of
      homologous or heterologous virus-specific binding and neutralizing antibodies
      compared to the untreated vaccine. Also, low pH treated influenza viral antigen
      showed lower antigenicity compared to the untreated influenza viral antigen.
      Lower efficacy of cross-protection against heterosubtypic virus was observed in
      the low-pH treated vaccine group. The results provide evidence that there is a
      correlation between protective efficacy and the stability of vaccines.

PMID- 21722935
TI  - An infectious disease of ducks caused by a newly emerged Tembusu virus strain in
      mainland China.
AB  - During investigations into an outbreak of egg production decline, retarded
      growth, and even death among ducks in Southeast China, a novel Tembusu virus
      strain named Tembusu virus Fengxian 2010 (FX2010) was isolated. This virus
      replicated in embryonated chicken eggs and caused embryo death. In cross
      neutralization tests, antiserum to the partial E protein of Tembusu virus Mm1775
      strain neutralized FX2010, whereas antiserum to Japanese encephalitis virus did
      not. FX2010 is an enveloped RNA virus of approximately 45-50 nm in diameter.
      Sequence analysis of its E and NS5 genes showed that both genes share up to 99.6%
      nucleotide sequence identity with Baiyangdian virus, and up to 88% nucleotide
      sequence identity with their counterparts in Tembusu virus. FX2010 was
      transmitted without mosquito, and caused systemic infection and lesions in
      experimentally infected ducks. These results indicate that FX2010 and BYD virus
      are newly emerged Tembusu virus strains that cause an infectious disease in
      ducks.

PMID- 21722936
TI  - Retrospective of ecological approaches to excess sludge reduction.
AB  - The problem of excess sludge handling produced during wastewater treatment is
      undeniable reality of grave concern with increasingly stringent legislations. The
      sludge synthesis yield being 0.4-0.6 kgVSS/kgCOD (0.57-0.8 kgCODcell/kgCOD),
      results in high power consumption on its digestion and therefore taken
      considerable attention to achieve sustainable strategies. Solids reduction by
      physico-chemical methods results in buildup of chemicals. This may present risk
      to the environment and may require further treatment to remove the chemicals of
      concern in future. Wastewater sludge reduction upto 100% by biological,
      sustainable, non-hazardous, and environment friendly methods has been
      successfully tested at different levels. Therefore, above reasons were sufficient
      driving forces to confine this review to non-chemically assisted processes.
      Similarly, the thermally assisted processes result in high carbon footprint and
      excluded from the scope of this review. Enough has been reviewed on sludge
      reduction, as numbers of articles on the same subject with different angles have
      been reported, still the progress in the last few years is missing; hence,
      special emphasis is given herewith to highlight the efforts of the last five
      years.

PMID- 21722937
TI  - Perfluorinated compounds in surface waters and WWTPs in Shenyang, China: mass
      flows and source analysis.
AB  - Concentrations of 10 perfluorinated chemicals (PFCs) were investigated in the Hun
      River (HR), four canals, ten lakes, and influents and effluents from four main
      municipal wastewater treatment plants (WWTPs) in Shenyang, China. Mass flows of
      four main PFCs were calculated to elucidate the contribution from different
      sections of the HR. Overall, perfluorooctanoic acid (PFOA) and perfluorohexanoic
      acid (PFHxA) were the major PFCs in the HR, with ranges of 2.68-9.13 ng/L, and
      2.12-11.3 ng/L, respectively, while perfluorooctane sulfonate (PFOS) was detected
      at lower levels, ranging from 0.40 to 3.32 ng/L. The PFC concentrations in the HR
      increased after the river passes through two cities (Shenyang and Fushun),
      indicating cities are an important contributor for PFCs. Mass flow analysis in
      the HR revealed that PFC mass flows from Fushun are 1.65-5.50 kg/year for C6-C8
      perfluorinated acids (PFCAs) and 1.29 kg/year for PFOS, while Shenyang
      contributed 2.83-5.18 kg C6-C8 PFCAs/year, and 3.65 kg PFOS/year. The
      concentrations of PFCs in four urban canals were higher than those in the HR,
      with the maximum total PFCs of 240 ng/L. PFOA and PFOS showed different trends
      along these canals, suggesting different sources for the two PFCs. Total PFCs in
      ten lakes from Shenyang were at low levels, with the greatest concentration (56.2
      ng/L) detected in a heavily industrialized area. The PFC levels in WWTP effluents
      were higher than those in surface waters with concentrations ranging from 18.4 to
      41.1 ng/L for PFOA, and 1.69-3.85 ng/L for PFOS. Similar PFC profiles between
      effluents from WWTPs and urban surface waters were found. These results indicate
      that WWTPs are an important PFC source in surface water. Finally, we found that
      the composition profiles of PFCs in surface waters were similar to those in tap
      water, but not consistent with those in adult blood from Shenyang. The
      calculation on total daily intake of PFOS by adults from Shenyang showed that the
      contribution of drinking water to human exposure was minor.

PMID- 21722938
TI  - Bioassays as a tool for evaluating advanced oxidation processes in water and
      wastewater treatment.
AB  - Advanced oxidation processes (AOPs) have been widely used in water and wastewater
      treatment for the removal of organic and inorganic contaminants as well as to
      improve biodegradability of industrial wastewater. Unfortunately, the partial
      oxidation of organic contaminants may result in the formation of intermediates
      more toxic than parent compounds. In order to avoid this drawback, AOPs are
      expected to be carefully operated and monitored, and toxicity tests have been
      used to evaluate whether effluent detoxification takes place. In the present
      work, the effect of AOPs on the toxicity of aqueous solutions of different
      classes of contaminants as well as actual aqueous matrices are critically
      reviewed. The dualism toxicity-biodegradability when AOPs are used as pre
      treatment step to improve industrial wastewater biodegradability is also
      discussed. The main conclusions/remarks include the followings: (i) bioassays are
      a really useful tool to evaluate the dangerousness of AOPs as well as to set up
      the proper operative conditions, (ii) target organisms for bioassays should be
      chosen according to the final use of the treated water matrix, (iii) acute
      toxicity tests may be not suitable to evaluate toxicity in the presence of
      low/realistic concentrations of target contaminants, so studies on chronic
      effects should be further developed, (iv) some toxicity tests may be not useful
      to evaluate biodegradability potential, in this case more suitable tests should
      be applied (e.g., activated sludge bioassays, respirometry).

PMID- 21722939
TI  - Estrogen receptor mediated activity in bankside groundwater, with flood suspended
      particulate matter and floodplain soil - an approach combining tracer substance,
      bioassay and target analysis.
AB  - Bankside groundwater is widely used as drinking water resource and, therefore,
      contamination has to be avoided. In the European Union groundwater protection is
      explicit subject to Water Framework Directive. While groundwater pollution may
      originate from different sources, this study investigated on impacts via flood
      events. Groundwater was sampled with increasing distance to the river Rhine near
      Karlsruhe, Germany. Samples were HPLC-MS-MS analyzed for the river contaminant
      carbamazepine to indicate river water infiltration, giving permanent presence in
      250 m distance to the river (14-47 MUg L-1). Following a flood event,
      concentrations of about 16-20 MUg L-1 could also be detected in a distance of 750
      m to the river. Furthermore, estrogenic activity as determined with the Yeast
      Estrogen Screen assay was determined to increase up to a 17beta-ethinylestradiol
      equivalent concentration (E-EQ)=2.9 ng L-1 near the river, while activity was
      initially measured following the flood with up to E-EQ=2.6 ng L-1 in 750 m
      distance. Detections were delayed with increasing distance to the river
      indicating river water expansion into the aquifer. Flood suspended matter and
      floodplain soil were fractionated and analyzed for estrogenic activity in
      parallel giving up to 1.4 ng g-1 and up to 0.7 ng g-1, respectively. Target
      analysis focusing on known estrogenic active substances only explained < 1% of
      measured activities. Nevertheless, river water infiltration was shown deep into
      bankside groundwater, thus, impacting groundwater quality. Therefore, flood
      events have to be in the focus when aiming for groundwater and drinking water
      protection as well as for implementation of Water Framework Directive.

PMID- 21722940
TI  - Changes in arsenic fractionation, bioaccessibility and speciation in organo
      arsenical pesticide amended soils as a function of soil aging.
AB  - Although organoarsenical pesticides are being phased out, sites with high
      concentrations of organic arsenical residues still exist due to the long-term
      application of these pesticides. The biotic and abiotic speciation of
      dimethylarsinic acid (DMA) can result in the formation of inorganic arsenic (As)
      species. Oxidation state, retention, and thereby persistence, varies according to
      temporal changes, influencing the availability and toxicity of contaminants. The
      current greenhouse study aimed at evaluating temporal changes in the oxidation
      state of As, geochemical partitioning, and bioaccessibility. Four soils with
      varying physiochemical properties were contaminated with DMA at two
      concentrations (675 and 1,500 mg kg(-1) of As). Rice plants were grown for a 6
      months period, following which, the soils were allowed to age. The operationally
      defined forms of As and its bioaccessibility was analyzed at 0, 6 months, 1 year,
      and 3 years. Changes in oxidation state of As were evaluated immediately after
      spiking and after 3 years of soil-pesticide equilibration. Results show that
      geochemical partitioning of As was affected significantly (P<0.05) by soil type,
      loading rates, and equilibration time. Arsenic was bound mainly to the poorly
      crystalline Fe/Al-oxyhydroxides in the soil. However, these interactions did not
      affect As bioaccessibility, presumably due to the dissolution of the bound
      fractions of As in the acidic stomach. While 74-94% of the total bioaccessible As
      was transformed to As(V), 4-19% was transformed to the more toxic As(III). This
      study indicates that although aging affected the geochemical partitioning of As
      in the soil, bioaccesibility was controlled by the gastric pH.

PMID- 21722941
TI  - Accumulation levels and characteristics of some pesticides in human adipose
      tissue samples from Southeast China.
AB  - This paper presents a comprehensive study of pesticide levels and bio
      accumulation characteristics in human adipose tissues among residents of
      Southeast China. A large number of adipose samples (n=633) were selected for 58
      pesticides and were analyzed by high sensitive Gas Chromatography-Tandem Mass
      Spectrometry (GC-MS/MS). The results showed that POPs pesticides were frequently
      detected, including 2,4'-DDD, 2,4'-DDE, 2,4'-DDT, 4,4'-DDD, 4,4'-DDE, 4,4'-DDT,
      alpha-HCH, beta-HCH, gamma-HCH, delta-HCH, hexachlorobenzene (HCB), and mirex.
      Other detected pesticide species were dicofol, methamidophos and chlordimeform,
      which have rarely been reported. Comparing to different countries, the
      concentrations of total DDT and HCH in these three Chinese southeastern sites
      were in the middle range, whereas the HCB and mirex were in the lower end. A
      significant correlation was observed between region as well as age and POPs
      pesticide levels. Some pesticide residue levels were also found significantly
      correlated to occupation. However, there was no significant correlation between
      gender and pesticides. Meanwhile, it is interesting to find that mortality of
      malignant tumors tends to associate with the pesticides levels in human adipose
      tissue. More importantly, the measured data presented in this study provide
      realistic information which is useful for assessing human exposure to pesticides
      in the general population of Southeast China.

PMID- 21722942
TI  - Effects of additional treatment of sarpogrelate to aspirin therapy on platelet
      aggregation and plasma plasminogen activator inhibitor activity in patients with
      stable effort angina.
AB  - INTRODUCTION: Serotonin is secreted from platelets at sites of endothelial
      injury, where it promotes thrombogenic reactions. Serotonin is reported to be
      associated with not only coronary artery disease but also cardiac events.
      MATERIALS AND METHODS: We studied 33 patients with stable effort angina (SEA) (11
      patients with multivessel disease (MVD) and 22 patients with single vessel
      disease (SVD)) and 25 patients with chest pain syndrome (CPS). Sarpogrelate was
      administered to 22 of 33 patients with SEA in addition to aspirin therapy, and
      platelet aggregation, plasma serotonin concentration, and plasma plasminogen
      activator inhibitor (PAI) activity were measured before and 1 week after
      administration. RESULTS AND CONCLUSIONS: Serotonin level was higher in patients
      with MVD than in those with SVD (p<0.05) and in those with CPS (p<0.001). The
      formation of small-sized platelet aggregates was significantly higher in the high
      serotonin group than in the low serotonin group of SEA patients. The formation of
      large-sized platelet aggregates was significantly decreased by administration of
      sarpogrelate (P<0.05). The formation of small- or medium-sized aggregates was not
      significantly decreased. Plasma PAI activity decreased significantly (P<0.05)
      although the plasma serotonin concentration did not show significant change by
      administration of sarpogrelate. Plasma serotonin level is increased in relation
      to severity of coronary artery disease and plasma serotonin level is associated
      with increased platelet aggregation. Administration of sarpogrelate in addition
      to aspirin therapy reduces the increased platelet aggregation and PAI activity,
      and it may indicate that additional administration of sarpogrelate is useful for
      patients with SEA.

PMID- 21722943
TI  - Low yield of early postoperative imaging after anastomotic urethroplasty.
AB  - OBJECTIVES: To evaluate the necessity and clinical effect of posturethroplasty
      imaging. METHODS: We reviewed our database of all urethroplasties performed by a
      single surgeon at our referral center during a 2-year period. The patients
      underwent voiding cystourethrography at a mean of 24 days postoperatively. The
      data analyzed included patient history and demographics, operative details,
      imaging results, and clinical outcomes. RESULTS: From 2007 to 2009, 210 patients
      underwent urethral reconstruction at our center. The patients undergoing
      meatoplasty or staged repairs were excluded, leaving 156 patients with
      postoperative imaging studies for analysis. Of 110 anterior urethroplasties, 59
      (54%) consisted of excision and primary anastomosis, 28 (25%) an augmented
      anastomotic procedure, and 23 (21%) a pure ventral onlay with a flap or graft.
      All 46 posterior urethroplasties were performed with scar excision and primary
      anastomosis. Of the 156 patients, only 4 (3%) had extravasation on postoperative
      voiding cystourethrography (2 after posterior urethroplasty, 1 after augmented
      anastomosis, and 1 after ventral onlay)--all were successfully managed with
      catheter replacement and removal at a mean of 8 days afterward. None of the 59
      men undergoing excision and primary anastomosis demonstrated extravasation.
      CONCLUSIONS: Extravasation on posturethroplasty voiding cystourethrography is
      rare after approximately 3 weeks of catheter drainage. Imaging can be omitted
      after uncomplicated excision and primary anastomosis urethroplasty.

PMID- 21722944
TI  - Brachial flow-mediated dilation correlates with vardenafil response in
      hypertensive men with vasculogenic erectile dysfunction.
AB  - OBJECTIVES: To investigate whether vasculogenic erectile dysfunction (ED)
      severity and the clinical response to vardenafil were associated with structural
      and functional vascular changes in patients with uncomplicated hypertension.
      METHODS: Sexually active hypertensive men (n = 100), aged 50-70 years, completed
      the International Index of Erectile Function, Erection Function Domain (IIEF-EF)
      and were divided into 2 groups: 74 men with mild to moderate, moderate, or severe
      ED (IIEF-EF score <=18) and without major cardiovascular disease and 26 controls
      (IIEF-EF score >=25). Clinical and laboratory evaluations were performed,
      followed by measurement of the carotid intima-media thickness (IMT) and brachial
      flow-mediated dilation (FMD) before 4 attempts with 20 mg of vardenafil. The
      responders had >=50% positive answers on sexual encounter profile question 3.
      RESULTS: The carotid IMT was significantly greater and the FMD was significantly
      lower in patients with ED than in the control patients. The baseline IIEF-EF
      score correlated negatively with the carotid IMT (r = -0.48, P < .001) and with
      the Framingham score (r = -0.41, P < .001) among those with ED. After
      multivariate logistic regression analysis, the baseline IIEF score was
      independently and only associated with the carotid IMT (beta = 6.105, P = .019).
      Responders were younger, had a lower cardiovascular risk profile and carotid IMT,
      and greater baseline IIEF-EF score and FMD than did the nonresponders. On
      logistic regression analysis, the response to vardenafil was independently
      associated with the brachial FMD (beta = 1.085, P = .002). CONCLUSIONS: In
      hypertensive men with vasculogenic ED and no other clinical evidence of
      arteriosclerosis, the ED severity correlated with the carotid IMT, and
      phosphodiesterase-5 effectiveness correlated with brachial FMD.

PMID- 21722945
TI  - Pelvic angiomyolipoma.
AB  - Angiomyolipoma is a rare benign tumor most commonly found in the kidney and,
      infrequently, extrarenally. We report a case of pelvic angiomyolipoma in a male
      patient without stigmata of tuberous sclerosis. The patient presented with right
      retroperitoneal bleeding and was found to have bilateral renal angiomyolipomas as
      well as a pelvic mass with similar appearance as the other lesions. He underwent
      urgent embolization of the large right angiomyolipoma and subsequent robot
      assisted left laparoscopic partial nephrectomy with simultaneous resection of the
      pelvic mass, which was well-tolerated. Pathology confirmed what is, to our
      knowledge, the only reported case of pelvic angiomyolipoma.

PMID- 21722946
TI  - Are stone protocol computed tomography scans mandatory for children with
      suspected urinary calculi?
AB  - OBJECTIVE: To examine the clinical utility of noncontrast-enhanced computed
      tomography (NCCT) in pediatric patients with urolithiasis who progressed to
      surgery. Although NCCT is routine for the evaluation of adult patients with
      suspected urolithiasis, its routine use in the pediatric population is tempered
      by concern about radiation exposure. METHODS: We conducted a retrospective chart
      review of all pediatric patients who had undergone surgery for urinary stones
      from 2003 to 2008 at our institution. The imaging modalities used, surgery type,
      stone composition, 24-hour urinalyses, and relevant predisposing conditions were
      characterized. RESULTS: A total of 42 pediatric patients (24 males and 18
      females) were treated during the 6-year period. The average age was 11.3+/-5.3
      years (range 2.7-25.4), and the most common treatment modalities were shock wave
      lithotripsy (28%) and ureteroscopy (22%). A discernible risk factor or cause of
      urolithiasis was absent in 21 patients (47%). A review of imaging studies found
      38 with stones visible on ultrasonography and/or abdominal plain film. A total of
      21 patients underwent NCCT, in addition to ultrasonography and/or abdominal plain
      film. Of these, only 5 patients required NCCT for the diagnosis or management of
      their stone. CONCLUSION: Nearly 90% of pediatric patients treated for symptomatic
      urolithiasis could have completed their evaluation and treatment without
      undergoing NCCT. For children who present with signs and symptoms suggesting
      urinary calculi, an initial evaluation and imaging with ultrasonography and
      abdominal plain film might suffice, avoiding the radiation of NCCT.

PMID- 21722947
TI  - NEMO is a key component of NF-kappaB- and IRF-3-dependent TLR3-mediated immunity
      to herpes simplex virus.
AB  - BACKGROUND: Children with germline mutations in Toll-like receptor 3 (TLR3),
      UNC93B1, TNF receptor-associated factor 3, and signal transducer and activator of
      transcription 1 are prone to herpes simplex virus-1 encephalitis, owing to
      impaired TLR3-triggered, UNC-93B-dependent, IFN-alpha/beta, and/or IFN-lambda
      mediated signal transducer and activator of transcription 1-dependent immunity.
      OBJECTIVE: We explore here the molecular basis of the pathogenesis of herpes
      simplex encephalitis in a child with a hypomorphic mutation in nuclear factor
      kappaB (NF-kappaB) essential modulator, which encodes the regulatory subunit of
      the inhibitor of the Ikappabeta kinase complex. METHODS: The TLR3 signaling
      pathway was investigated in the patient's fibroblasts by analyses of IFN-beta,
      IFN-lambda, and IL-6 mRNA and protein levels, by quantitative PCR and ELISA,
      respectively, upon TLR3 stimulation (TLR3 agonists or TLR3-dependent viruses). NF
      kappaB activation was assessed by electrophoretic mobility shift assay and
      interferon regulatory factor 3 dimerization on native gels after stimulation with
      a TLR3 agonist. RESULTS: The patient's fibroblasts displayed impaired responses
      to TLR3 stimulation in terms of IFN-beta, IFN-lambda, and IL-6 production, owing
      to impaired activation of both NF-kappaB and IRF-3. Moreover, vesicular
      stomatitis virus, a potent IFN-inducer in human fibroblasts, and herpes simplex
      virus-1, induced only low levels of IFN-beta and IFN-lambda in the patient's
      fibroblasts, resulting in enhanced viral replication and cell death, as reported
      for UNC-93B-deficient fibroblasts. CONCLUSION: Herpes simplex encephalitis may
      occur in patients carrying NF-kappaB essential modulator mutations, due to the
      impairment of NF-kappaB- and interferon regulatory factor 3-dependent-TLR3
      mediated antiviral IFN production.

PMID- 21722948
TI  - Thymine DNA glycosylase is essential for active DNA demethylation by linked
      deamination-base excision repair.
AB  - DNA methylation is a major epigenetic mechanism for gene silencing. Whereas
      methyltransferases mediate cytosine methylation, it is less clear how
      unmethylated regions in mammalian genomes are protected from de novo methylation
      and whether an active demethylating activity is involved. Here, we show that
      either knockout or catalytic inactivation of the DNA repair enzyme thymine DNA
      glycosylase (TDG) leads to embryonic lethality in mice. TDG is necessary for
      recruiting p300 to retinoic acid (RA)-regulated promoters, protection of CpG
      islands from hypermethylation, and active demethylation of tissue-specific
      developmentally and hormonally regulated promoters and enhancers. TDG interacts
      with the deaminase AID and the damage response protein GADD45a. These findings
      highlight a dual role for TDG in promoting proper epigenetic states during
      development and suggest a two-step mechanism for DNA demethylation in mammals,
      whereby 5-methylcytosine and 5-hydroxymethylcytosine are first deaminated by AID
      to thymine and 5-hydroxymethyluracil, respectively, followed by TDG-mediated
      thymine and 5-hydroxymethyluracil excision repair.

PMID- 21722949
TI  - Estimate of the population of preantral follicles in the ovaries of Bos taurus
      indicus and Bos taurus taurus cattle.
AB  - The number of oocytes recovered from Bos taurus indicus females subjected to ovum
      pick-up averaged two to four times greater compared to Bos taurus taurus females.
      The objective of the present study was to test the hypothesis that this
      difference in oocyte yield was due to more preantral follicles in the ovaries of
      Bos indicus females. Ovaries (n = 64) from Nelore (Bos indicus) fetuses (n = 10),
      heifers (n = 12), and cows (n = 10), and Aberdeen Angus (Bos taurus) fetuses (n =
      10), heifers (n = 12), and cows (n = 10) were cut longitudinally into halves,
      fixed, and processed for histological evaluation. The number of preantral
      follicles was estimated by counting them in each histological section, using the
      oocyte nucleus as a marker and employing a correction factor. The average number
      of preantral follicles in the ovaries of Bos indicus vs Bos taurus was (mean +/-
      SD) 143,929 +/- 64,028 vs 285,155 +/- 325,195 for fetuses, 76,851 +/- 78,605 vs
      109,673 +/- 86,078 for heifers, and 39,438 +/- 31,017 vs 89,577 +/- 86,315 for
      cows (P > 0.05). The number of preantral follicles varied greatly among
      individual animals within the same category, as well as between breeds. In
      conclusion, we inferred that the higher oocyte yield from Bos indicus females was
      not due to a greater ovarian reserve of preantral follicles. Therefore,
      mechanisms controlling follicle development after the preantral stage likely
      accounted for differences between Bos indicus and Bos taurus females in number of
      oocytes retrieved at ovum pick-up.

PMID- 21722950
TI  - Risk of onlay fracture during pre-cementation functional occlusal tapping.
AB  - OBJECTIVE: To evaluate in vitro the pre-cementation resistance of CAD/CAM onlays
      subjected to functional occlusal tapping. METHODS: An extracted tooth model
      (molar and premolar) with simulated bone and periodontal ligament was used to
      make a mesio-occlusal onlay preparation (two mesial cusps covered). Immediate
      dentin sealing was applied to the prepared tooth. The corresponding onlays were
      fabricated with Cerec either using composite resin (Paradigm MZ100) or ceramic
      (e.max CAD and Mark II) (n=14). An elevated marginal ridge was designed with the
      intention of generating hyper-occlusion. Pre-cementation occlusal tapping was
      simulated using closed-loop servo-hydraulics at 2 Hz, starting with a load of 40
      N, followed by 80, 120, 160, 200, 240 and 280 N (10 cycles each). All samples
      were loaded until fracture or to a maximum of 70 cycles. Groups were compared
      using the life table survival analysis (p=.016, Bonferroni method). RESULTS:
      Survival probability was MZ100>e.max CAD>Mark II. The restorations made from
      e.max CAD and Mark II failed at an average load of 157 N and 123 N, respectively
      with no specimen withstanding all 70 load cycles (survival 0%); with MZ100 the
      survival rate was 36%. SIGNIFICANCE: Material selection has a significant effect
      on the risk of CAD/CAM onlay fracture during pre-cementation functional occlusal
      tapping with composite resin onlays showing the minimum risk compared to ceramic
      ones.

PMID- 21722951
TI  - Text messaging in smoking cessation: the txt2stop trial.

PMID- 21722952
TI  - Smoking cessation support delivered via mobile phone text messaging (txt2stop): a
      single-blind, randomised trial.
AB  - BACKGROUND: Smoking cessation programmes delivered via mobile phone text
      messaging show increases in self-reported quitting in the short term. We assessed
      the effect of an automated smoking cessation programme delivered via mobile phone
      text messaging on continuous abstinence, which was biochemically verified at 6
      months. METHODS: In this single-blind, randomised trial, undertaken in the UK,
      smokers willing to make a quit attempt were randomly allocated, using an
      independent telephone randomisation system, to a mobile phone text messaging
      smoking cessation programme (txt2stop), comprising motivational messages and
      behavioural-change support, or to a control group that received text messages
      unrelated to quitting. The system automatically generated intervention or control
      group texts according to the allocation. Outcome assessors were masked to
      treatment allocation. The primary outcome was self-reported continuous smoking
      abstinence, biochemically verified at 6 months. All analyses were by intention to
      treat. This study is registered, number ISRCTN 80978588. FINDINGS: We assessed
      11,914 participants for eligibility. 5800 participants were randomised, of whom
      2915 smokers were allocated to the txt2stop intervention and 2885 were allocated
      to the control group; eight were excluded because they were randomised more than
      once. Primary outcome data were available for 5524 (95%) participants.
      Biochemically verified continuous abstinence at 6 months was significantly
      increased in the txt2stop group (10.7% txt2stop vs 4.9% control, relative risk
      [RR] 2.20, 95% CI 1.80-2.68; p<0.0001). Similar results were obtained when
      participants that were lost to follow-up were treated as smokers (268 [9%] of
      2911 txt2stop vs 124 [4%] of 2881 control [RR 2.14, 95% CI 1.74-2.63; p<0.0001]),
      and when they were excluded (268 [10%] of 2735 txt2stop vs 124 [4%] of 2789
      control [2.20, 1.79-2.71; p<0.0001]). No significant heterogeneity was shown in
      any of the prespecified subgroups. INTERPRETATION: The txt2stop smoking cessation
      programme significantly improved smoking cessation rates at 6 months and should
      be considered for inclusion in smoking cessation services. FUNDING: UK Medical
      Research Council, Primary Care Research Networks.

PMID- 21722953
TI  - The effect of composition of calcium phosphate composite scaffolds on the
      formation of tooth tissue from human dental pulp stem cells.
AB  - Different approaches towards making 3-dimensional (3-D) bioengineered tooth for
      future replacement therapy have been developed including scaffold-based tooth
      regeneration. However, selection of optimal scaffold for future clinical
      application remains a challenge. In the present study, we tested biocompatibility
      of four different types of 3-D scaffolds for tooth-tissue regeneration, including
      a pure poly(lactide-co-glycolide) (PLGA) (70/30, mol/mol) scaffold and three
      types of calcium phosphate contained composites scaffolds that were 50 wt% of
      PLGA combined with 50 wt% of hydroxyapatite (HA), tricalcium phosphate (TCP) or
      calcium carbonate hydroxyapatite (CDHA) respectively. These scaffolds were
      fabricated by the particle leaching in combination with phase separation
      technology. Surface modification of these scaffolds was further performed by an
      ammonia plasma treatment and anchorage of collagen technology. Effect of
      composition of the composite scaffolds on proliferation of human dental pulp stem
      cells (DPSCs) was accessed using in vitro MTT assay and in vivo BrdU labeling.
      Differentiation capability of the DPSCs in the scaffolds was analyzed by
      measurement of the levels of calcified tissue formation and ALP activity. Our
      results showed that while the calcium phosphate contained compound is able to
      support regeneration of tooth tissue effectively, the PLGA/TCP scaffold is more
      appropriate for the proliferation and differentiation of DPSCs. Furthermore,
      seeding of dissociated 4-dpn rat tooth bud cells on the PLGA/TCP scaffold
      generated dentin- and pulp-like tissues. Our results demonstrate that the
      PLGA/TCP scaffold is superior to the other three scaffolds for tooth-tissue
      regeneration, especially for dentin formation.

PMID- 21722954
TI  - Reduced uterine perfusion pressure model is not successful to mimic severe
      preeclampsia.
AB  - The aim of the study was to investigate maternal (hemoglobin, hematocrit, and
      biochemical parameters of blood and urine) and fetal parameters (number and
      weight of alive fetus) of preeclampsia in a rat model. Placental oxidative stress
      markers (protein carbonyl, malondialdehyde) and placental antioxidant values
      (CuZn-superoxide dismutase, glutathione peroxidase) were also measured.
      Preeclampsia was induced experimentally in timed-pregnant Sprague-Dawley rats by
      using the reduced uterine perfusion pressure (RUPP) model. Placental oxidative
      stress that plays a key role in the pathophysiology of placenta-related
      disorders, most notably preeclampsia (PE) and intrauterine growth restriction
      (IUGR) were demonstrated by using RUPP model. On day 14 of gestation, silver
      clips were placed around the aorta below the renal arteries and on the left and
      right uterine arcade at the ovarian artery. In the RUPP model animals (n = 15),
      when compared with the normotensive controls (n = 15), arterial pressure on day
      19 of gestation was significantly higher in the RUPP rats (151.7 +/- 17.6 mmHg)
      than normal pregnant rats (113.9 +/- 11.4 mmHg). The RUPP rats showed a
      significant increase in protein excretion when compared with the normal pregnant
      rats (0.3 +/- 0.04 vs 0.47 +/- 0.07 g/dL) (p < 0.05). Associated with the
      hypertension in RUPP rats, placental levels of malondialdehyde (2.4 +/- 0.2 vs.
      1.6 +/- 0.2 umol/gm tissue) and protein carbonyl (1.4 +/- 0.3 vs. 0.9 +/- 0.3
      nmol/mg protein) were increased, while superoxid dismutase (0.03 vs 0.42 U/mg
      protein) and glutathione peroxidase (1.04 +/- 0.31 vs 0.76 +/- 0.22 U/g protein)
      were decreased. Pup number (6.6 +/- 3.1 vs. 9.93 +/- 2.0) and litter weight (17.4
      +/- 7.7 vs. 22.9 +/- 6.7 g) were lower in the preeclamptic group. None of the
      complete blood counts and biochemical values other than sodium and chlorine were
      significantly different in preeclamptic group. Our findings suggest that the RUPP
      model cannot mimic severe preeclampsia; however, further studies using different
      settings may be helpful to obtain a preeclampsia model that is capable of
      successfully producing severe preeclampsia findings.

PMID- 21722955
TI  - In adults with Prader-Willi syndrome, elevated ghrelin levels are more consistent
      with hyperphagia than high PYY and GLP-1 levels.
AB  - OBJECTIVE: Prader-Willi syndrome (PWS) is a leading genetic cause of obesity,
      characterized by hyperphagia, endocrine and developmental disorders. It is
      suggested that the intense hyperphagia could stem, in part, from impaired gut
      hormone signaling. Previous studies produced conflicting results, being
      confounded by differences in body composition between PWS and control subjects.
      DESIGN: Fasting and postprandial gut hormone responses were investigated in a
      cross-sectional cohort study including 10 adult PWS, 12 obese subjects matched
      for percentage body fat and central abdominal fat, and 10 healthy normal weight
      subjects. METHODS: PYY[total], PYY[3-36], GLP-1[active] and ghrelin[total] were
      measured by ELISA or radioimmunoassay. Body composition was assessed by dual
      energy X-ray absorptiometry. Visual analog scales were used to assess hunger and
      satiety. RESULTS: In contrast to lean subjects (p<0.05), PWS and obese subjects
      were similarly insulin resistant and had similar insulin levels. Ghrelin[total]
      levels were significantly higher in PWS compared to obese subjects before and
      during the meal (p<0.05). PYY[3-36] meal responses were higher in PWS than in
      lean subjects (p=0.01), but not significantly different to obese (p=0.08), with
      an additional non-significant trend in PYY[total] levels. There were no
      significant differences in self-reported satiety between groups, however PWS
      subjects reported more hunger throughout (p=0.003), and exhibited a markedly
      reduced meal-induced suppression of hunger (p=0.01) compared to lean or obese
      subjects. CONCLUSIONS: Compared to adiposity-matched control subjects,
      hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response.
      Elevated ghrelin levels in PWS are consistent with increased hunger and are
      unrelated to insulin levels.

PMID- 21722956
TI  - The two faces of myeloproliferative neoplasms: Molecular events underlying
      lymphoid transformation.
AB  - Multipotent haematopoietic stem cells pass through stages of differentiation with
      the progressive loss of developmental options leading to the production of
      terminally differentiated mature blood cells. This process is regulated by
      soluble cytokines binding to a ligand specific cell surface receptor on a
      precursor cell. Key to signal transduction are tyrosine kinase proteins which can
      be divided into two sub families, the receptor protein tyrosine kinases which are
      transmembrane receptors and retain an intact catalytic kinase domain and the
      cytoplasmic tyrosine kinases which bind to cytokine receptors. Abnormalities of
      tyrosine kinase proteins are well recognised in myeloid malignancies, mutation in
      the cytoplasmic tyrosine kinase JAK2 (V617F) is key in the pathogenesis of
      myeloproliferative neoplasms, and translocations involving ABL key in the
      development of chronic myeloid leukaemia. However tyrosine kinase mutations are
      increasingly recognised to play a role in the pathogenesis of a wider range of
      haematological cancers. This review focuses on the role of deregulated tyrosine
      kinase genes either as part of novel fusion proteins involving FGFR1, PDGFRalpha,
      PDGFRbeta, JAK2 and ABL, or as a consequence of point mutation in JAK1 or JAK2 in
      the development of precursor T and B lymphoid malignancies or mixed
      myeloid/lymphoid disorders. We also set out some of the postulated mechanisms
      which underlie the association of tyrosine kinase mutations with the development
      of lymphoid malignancy.

PMID- 21722957
TI  - Lifestyle adjustments of adults with long-term implantable left ventricular
      assist devices: a phenomenologic inquiry.
AB  - OBJECTIVE: To explore and describe the lifestyle adjustments made by adult
      recipients of a long-term implantable left ventricular assist device (LVAD).
      METHODS: A phenomenologic inquiry was used to uncover the lifestyle adjustments
      of 7 men and 2 women, ages 31 to 70 years, who had an LVAD for more than 3 months
      after hospital discharge. RESULTS: An overarching theme, "adjustment takes time,"
      represents the lifestyle adjustments of the study participants. Early adjustment
      was highlighted by participants' concerns with physical, psychologic, and
      environmental aspects, whereas late adjustment was highlighted by behaviors
      associated with acceptance of the LVAD as an integral component of their bodies
      and lives. CONCLUSION: This study provides insight into the patient's perspective
      regarding the challenges faced in living with an LVAD. The findings inform health
      care providers in the acute and critical care settings in assisting patients to
      positively adjust with the lifestyle imposed by an LVAD.

PMID- 21722958
TI  - A placebo- and active-controlled assessment of 6- and 50-mg oral doxepin on
      cardiac repolarization in healthy volunteers: a thorough QT evaluation.
AB  - BACKGROUND: Doxepin tablets have recently been approved in the United States in
      doses of 3 and 6 mg for the treatment of insomnia characterized by difficulty
      with sleep maintenance. OBJECTIVE: Because no previous thorough QT evaluation of
      doxepin has been conducted, the primary objective of this study was to assess the
      highest recommended dose (6 mg) and a supratherapeutic amount (50 mg) of doxepin
      on cardiac repolarization under steady-state conditions in healthy adult
      subjects. METHODS: Male and female volunteers aged 18 to 45 years were randomized
      to receive double-blind doxepin or placebo for 7 days, or 6 days of double-blind
      placebo before one open-label administration of 400-mg moxifloxacin on day 7.
      Holter electrocardiograms were collected at baseline and on day 7 for up to 23.5
      hours after dosing; the results were read at a central facility. The primary
      outcome measure was the time-matched change from baseline in individually
      corrected QT (QTcI) intervals. Additional outcome measures were used to evaluate
      outlying QTc values and the relationship of QTcI to plasma concentrations of
      doxepin and its primary demethylated metabolite, nordoxepin. RESULTS: A total of
      206 healthy subjects (108 women, 98 men) were randomized to a study group; 192
      subjects (93.2%) received all scheduled administrations of study drug, and 190
      subjects (92.2%) completed the study. The study population was 47.6% male and
      52.4% female, and the mean age was 30.3 years. Neither amount of administered
      doxepin increased QTcI, nor did the upper bound of the 95% CIs for the point
      estimates exceed 10 milliseconds at any time point. The results for moxifloxacin
      met the assay sensitivity criteria for a positive control. The predicted placebo
      corrected change in QTcI at the mean doxepin C(max) values for both administered
      amounts (6 mg: -0.88 millisecond [upper CI: 0.37 millisecond]; 50 mg, 2.38
      milliseconds [upper CI: 4.00 milliseconds]) did not suggest an effect on cardiac
      repolarization, and no doxepin-treated subject met specific criteria for outlying
      QTc values. CONCLUSION: This thorough QT study revealed no effects of doxepin on
      QTcI up to 50 mg, suggesting that doxepin therapy for insomnia is unlikely to
      increase QTc intervals.

PMID- 21722959
TI  - Repeated and escalating preoperative subanesthetic doses of ketamine for
      postoperative pain control in patients undergoing tumor resection: a randomized,
      placebo-controlled, double-blind trial.
AB  - BACKGROUND: Ketamine induces a short-term effect on postoperative pain when
      administered intravenously immediately before or during acute pain. Repeated
      administration of low-dose ketamine may induce long-term pain relief in chronic
      pain syndromes. OBJECTIVE: The aim of our study was to determine whether
      ketamine's effect on acute postoperative pain could be enhanced and prolonged and
      analgesia consumption reduced if it was administered intramuscularly in repeated
      and escalating subanesthetic doses many hours before surgery. METHODS: Patients
      who were scheduled for tumor resection under general anesthesia were randomly and
      blindly given preoperative IM ketamine (K) or normal saline (placebo [P])
      following 1 of 3 consecutive protocols (2 groups/protocol, 20 patients/group): 1
      dose (25-mg ketamine or 1-mL saline) at 4 hours preoperatively (K1 or P1); 2
      doses (10- and 25-mg ketamine or 1-mL saline twice) at 11 and 4 hours (K2 or P2);
      or 3 doses (5-, 10-, and 25-mg ketamine or 1-mL saline thrice) at 17, 11, and 4
      hours preoperatively (K3 or P3). No other preoperative medications were given.
      Postoperatively, all patients received morphine (1.5 mg/bolus) via an intravenous
      patient-controlled analgesia (PCA) device. RESULTS: A total of 120 patients took
      part in the study. Patients' ages ranged from 15 to 75 years; mean weight (76
      [14] kg; range, 50-120), gender (69 men, 51 women), and race were equally
      distributed among the groups. There were no significant differences in
      intraoperative parameters among the groups. The patients' mean self-rated 48-hour
      pain scores on a numerical rating scale were lower in the K2 and K3 groups than
      in their corresponding placebo groups (K2: 1.67 [1.04] vs P2: 3.62 [1.93] [P =
      0.0004]; K3: 2.22 [1.37] vs P3: 3.25 [1.76] [P = 0.046]). These groups also used
      ~35% less morphine compared with the placebo groups (K2: 28.4 [20.4] mg, K3: 26.6
      [16.0] mg vs P2: 42.4 [30.4] mg, P3: 40.9 [21.2] mg [P <= 0.02]). Intravenous PCA
      usage among K2 and K3 patients was ~50% less than the usage among their placebo
      counterparts (P < 0.05). The 1-ketamine-injection patients' pain scores and
      analgesic consumption were similar to those of their placebo groups. The 25-mg
      ketamine injections caused dizziness that lasted up to 2 minutes. CONCLUSIONS:
      Our 48-hour data suggest that 2 or 3 escalating subanesthetic doses of IM
      ketamine injected consecutively hours before surgery attenuated postoperative
      pain and reduced morphine consumption in these subjects.

PMID- 21722960
TI  - Pharmacokinetics of oral cyanocobalamin formulated with sodium N-[8-(2
      hydroxybenzoyl)amino]caprylate (SNAC): an open-label, randomized, single-dose,
      parallel-group study in healthy male subjects.
AB  - BACKGROUND: Vitamin B12 (cobalamin) deficiency may be caused by inadequate
      dietary intake of B12 or by conditions that result in malabsorption of the
      vitamin. Crystalline vitamin B12, usually in the form of cyanocobalamin, is
      administered parenterally (ie, intramuscularly) or orally for treating deficiency
      states. Intramuscular administration is widely accepted as a treatment method.
      Oral B12 supplementation is also used, but it is considered to be less reliable.
      OBJECTIVE: This study was conducted to compare the pharmacokinetics and
      tolerability of 2 oral formulations of cyanocobalamin-a marketed cyanocobalamin
      tablet (immediate-release B12 5 mg) and cyanocobalamin formulated with a
      proprietary carrier, sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC)-to
      establish the feasibility of using an absorption enhancer with B12 to improve
      uptake of the vitamin. This was the first clinical study conducted with the
      cyanocobalamin/SNAC coformulation. METHODS: An open-label, randomized, single
      dose, parallel-group study was conducted in healthy male subjects. Subjects were
      randomly assigned to 1 of 4 treatment groups: Treatment A subjects (n = 4)
      received 2 tablets of 5-mg cyanocobalamin formulated with 100-mg SNAC as part of
      a dose range-finding arm included to determine a dose to provide a measurable
      concentration of vitamin B12 at all time points when tested with the available
      vitamin B12 assay; treatment B subjects (n = 6) received 1 tablet of 5-mg
      cyanocobalamin formulated with 100-mg SNAC; treatment C subjects (n = 6) received
      1 commercially available 5-mg cyanocobalamin tablet; and treatment D subjects (n
      = 4) received commercially available 1-mg cyanocobalamin IV. Treatment A was
      completed 3 weeks before treatments B, C, and D were studied. Human serum B12 was
      analyzed by chemiluminescence assay method. Validation procedures established
      that samples could be diluted up to 100 times without any effects on accuracy and
      precision. The pharmacokinetic properties of vitamin B12 were characterized by
      noncompartmental analysis. Vitamin B12 absolute bioavailability estimates were
      calculated between the oral (A, B, and C) and IV (D) treatments using non
      baseline-adjusted vitamin B12 concentrations as well as baseline-adjusted vitamin
      B12 concentrations, with or without body weight adjustments. Tolerability was
      evaluated through review or monitoring of medical history, physical examination
      findings, concomitant medications, vital signs, laboratory tests (hematology,
      serum chemistry, and urinalysis values), electrocardiography, adverse events, and
      serious adverse events. RESULTS: Twenty healthy male subjects, aged 20 to 45
      years, participated in this study. Based on data from treatment A, a 5-mg
      cyanocobalamin dose was selected for use with treatments B and C. The oral
      cyanocobalamin formulation containing SNAC had greater mean absolute
      bioavailability than the commercial oral formulation (5.09% vs 2.16%,
      respectively), calculated on AUC(0-last) values uncorrected for baseline, weight,
      or body mass index. It also had a reduced T(max) compared with the commercial
      formulation (0.5 hours vs 6.83 hours, respectively). The K(e) was similar between
      treatments (0.028 1/h vs 0.025 1/h). Comparable results were achieved using
      corrected values. The cyanocobalamin/SNAC formulation was well tolerated, and
      there were no reported adverse events. CONCLUSIONS: An oral formulation of 5-mg
      cyanocobalamin containing 100-mg SNAC, an absorption enhancer, provided
      significantly improved bioavailability and a significant decrease in T(max) for
      B12 in a small study of normal healthy subjects compared with a commercially
      available 5-mg cyanocobalamin oral formulation. Both oral formulations and
      commercial 1-mg cyanocobalamin IV were well tolerated.

PMID- 21722961
TI  - Bioremediation approaches for organic pollutants: a critical perspective.
AB  - Due to human activities to a greater extent and natural processes to some extent,
      a large number of organic chemical substances such as petroleum hydrocarbons,
      halogenated and nitroaromatic compounds, phthalate esters, solvents and
      pesticides pollute the soil and aquatic environments. Remediation of these
      polluted sites following the conventional engineering approaches based on
      physicochemical methods is both technically and economically challenging.
      Bioremediation that involves the capabilities of microorganisms in the removal of
      pollutants is the most promising, relatively efficient and cost-effective
      technology. However, the current bioremediation approaches suffer from a number
      of limitations which include the poor capabilities of microbial communities in
      the field, lesser bioavailability of contaminants on spatial and temporal scales,
      and absence of bench-mark values for efficacy testing of bioremediation for their
      widespread application in the field. The restoration of all natural functions of
      some polluted soils remains impractical and, hence, the application of the
      principle of function-directed remediation may be sufficient to minimize the
      risks of persistence and spreading of pollutants. This review selectively
      examines and provides a critical view on the knowledge gaps and limitations in
      field application strategies, approaches such as composting,
      electrobioremediation and microbe-assisted phytoremediation, and the use of
      probes and assays for monitoring and testing the efficacy of bioremediation of
      polluted sites.

PMID- 21722962
TI  - Adverse effects in wild fish living downstream from pharmaceutical manufacture
      discharges.
AB  - A set of biochemical and histological responses was measured in wild gudgeon
      collected upstream and downstream of urban and pharmaceutical manufacture
      effluents. These individual end-points were associated to fish assemblage
      characterisation. Responses of biotransformation enzymes, neurotoxicity and
      endocrine disruption biomarkers revealed contamination of investigated stream by
      a mixture of pollutants. Fish from sampled sites downstream of the industrial
      effluent exhibited also strong signs of endocrine disruption including
      vitellogenin induction, intersex and male-biased sex-ratio. These individual
      effects were associated to a decrease of density and a lack of sensitive fish
      species. This evidence supports the hypothesis that pharmaceutical compounds
      discharged in stream are involved in recorded endocrine disruption effects and
      fish population disturbances and threaten disappearance of resident fish species.
      Overall, this study gives argument for the utilisation of an effect-based
      monitoring approach to assess impacts of pharmaceutical manufacture discharges on
      wild fish populations.

PMID- 21722963
TI  - Chemistry as the defining science: discipline and training in nineteenth-century
      chemical laboratories.
AB  - The institutional revolution has become a major landmark of late-nineteenth
      century science, marking the rapid construction of large, institutional
      laboratories which transformed scientific training and practice. Although it has
      served historians of physics well, the institutional revolution has proved much
      more contentious in the case of chemistry. I use published sources, mainly
      written by chemists and largely focused on laboratories built in German-speaking
      lands between about 1865 and 1900, to show that chemical laboratory design was
      inextricably linked to productive practice, large-scale pedagogy and disciplinary
      management. I argue that effective management of the novel risks inherent in
      teaching and doing organic synthesis was significant in driving and shaping the
      construction of late-nineteenth century institutional chemical laboratories, and
      that these laboratories were essential to the disciplinary development of
      chemistry. Seen in this way, the laboratory necessarily becomes part of the
      material culture of late-nineteenth century chemistry, and I show how this view
      leads not only to a revision of what is usually known as the laboratory
      revolution in chemistry but also to a new interpretation of the institutional
      revolution in physics.

PMID- 21722964
TI  - Mannan-binding lectin-2 (MBL2) gene polymorphisms in prenatal and perinatal
      cytomegalovirus infections.
AB  - Cytomegalovirus (CMV) is the leading cause of congenital infections among
      neonates. About 10% of newborns with such an infection have clinical symptoms at
      birth and about 1% of infected fetuses die due to developmental malformations.
      Mannan-binding lectin (MBL) is considered to be an important factor in innate
      immunity. Its deficiency is believed to predispose to various (including viral)
      infections. The aim of this study was to investigate the possible role of MBL2
      gene polymorphisms in prenatal and perinatal CMV infections. The frequencies of
      MBL2 gene exon 1 mutations as well as MBL deficiency-associated variants
      (LXPA/O+O/O) among newborns with confirmed cytomegalovirus infection were not
      significantly lower than among non-infected individuals. The distribution of MBL2
      haplotypes was similar between the groups studied. These data suggest MBL does
      not have a major influence on susceptibility to prenatal or perinatal CMV
      infections.

PMID- 21722965
TI  - Experimental model of autoimmune orchitis with abdominal placement of donor's
      testes, epididymides, and vasa deferentia in recipient mice.
AB  - Haploid germ cells (spermatids and spermatozoa) develop in the testis after
      immune tolerance has been established. Therefore, they contain various
      autoimmunogenic antigens, but the testis is known to be an immunologically
      privileged organ. In particular, the blood-testis barrier formed by Sertoli cells
      protects autoimmunogenic haploid germ cells from attack by the autoimmune system.
      Experimental autoimmune orchitis (EAO), a breakdown of the testicular immune
      privilege leading to immunological male infertility, has been ordinarily induced
      in mice by immunization twice with testicular antigens+complete Freund's adjuvant
      (CFA)+Bordetella pertussis (BP). We previously found that two subcutaneous
      injections of viable syngeneic testicular germ cells induced murine EAO without
      the use of CFA+BP. In both EAO models, the lesions are characterized by
      spermatogenic disturbance with lymphocytic inflammation, and a second
      immunization with testicular antigens is critical for the disease induction. In
      the present study, we found that only one placement of a syngeneic donor's
      testes, epididymides and vasa deferentia (TEV) into the abdominal cavity or
      subcutaneous space was sufficient to induce EAO on the recipient's testes in
      mice. It was also noted that the placement of TEV induced only orchitis without
      epididymo-vasitis, while the serum autoantibodies were reactive with haploid germ
      cells existing throughout the TEV. Furthermore, the TEV placed in the abdominal
      cavity rather than the subcutaneous space was effective in inducing severe EAO,
      and the A/J strain was most susceptible to the TEV-induced EAO among the three
      strains examined. The model of EAO induced by the placement of the donor's TEV
      into the abdominal cavity in A/J mice will be helpful for the further analyses of
      testicular autoimmunity.

PMID- 21722966
TI  - Interferon-gamma expression in trophoblast cells in pregnant ewes challenged with
      Chlamydophila abortus.
AB  - Pregnant ewes were challenged with Chlamydia abortus at 91-98 days of gestation
      and euthanised at 14, 21 and 28 days post-challenge. IFNgamma mRNA labelling
      appeared to be co-localised with Chlamydial lipopolysaccharide within trophoblast
      cells in discrete areas lining the primary villi in the limbus and hilar zone of
      the placentomes from challenged sheep on days 21 and 28 post-infection. The
      presence of IFNgamma was also demonstrated by immunohistochemistry. No labelling
      was seen in tissues from the non-infected ewes. The presence of IFNgamma in
      trophoblast cells from infected ewes may indicate an attempt to restrict the
      replication of the organism and be an important trigger for the inflammatory
      responses that develop on the fetal side of the placenta in enzootic abortion.

PMID- 21722968
TI  - FIV associated neoplasms--a mini-review.
AB  - Retroviral induced neoplasms have been key to understanding oncogenesis and are
      important etiologic agents associated with cancer formation. Cats infected with
      feline immunodeficiency virus (FIV), the feline analogue to human
      immunodeficiency virus (HIV), are reported to be at increased incidence of
      neoplasia. This review highlights reported risk factors and tumor cell phenotypes
      associated with neoplasias arising in FIV-infected animals, differences in
      oncogenic disease in natural versus experimental FIV infections, and similarities
      between FIV- and HIV-related malignancies. The most common type of FIV-associated
      neoplasm reported in the literature is lymphoma, specifically of B-cell origin,
      with experimentally infected cats developing neoplastic lesions at an earlier age
      than their naturally infected cohorts. The mechanism of FIV-induced lymphoma has
      not been completely ascertained, though the majority of published studies
      addressing this issue suggest oncogenesis arises via indirect mechanisms. HIV
      infected individuals have increased risk of neoplasia, specifically B cell
      lymphoma, in comparison with uninfected individuals. Additional similarities
      between FIV- and HIV-associated neoplasms include the presence of extranodal
      lymphoma, a synergism with other oncogenic viruses, and an apparent indirect
      mechanism of induced oncogenesis. This literature supports study of FIV
      associated neoplasms to further characterize this lentiviral-neoplasia
      association for the benefit of both human and animal disease, and to advance our
      general knowledge of mechanisms for viral-induced oncogenesis.

PMID- 21722967
TI  - Persistence after birth of systemic inflammation associated with umbilical cord
      inflammation.
AB  - Intrauterine inflammation is followed by elevated concentrations of inflammation
      related proteins in the newborn's blood. Many of these proteins have short half
      lives. The persistence of this postnatal inflammation has not previously been
      investigated. In a sample of 834 infants born before the 28th week of gestation,
      12% (103) had grade 1 or 2, and 17% (142) had grade 3, 4, or 5 umbilical cord
      inflammation. Concentrations of nine proteins previously shown to be associated
      with umbilical cord inflammation at birth were measured on the first postnatal
      day and at two weekly intervals after birth. We evaluated the hypothesis that
      children who had umbilical cord inflammation were no more likely than others to
      have elevated concentrations of inflammation-related proteins in postnatal blood.
      The concentrations of seven of the nine proteins [C-reactive protein (CRP),
      myeloperoxidase (MPO), IL1beta, IL8, TNFalpha, intercellular adhesion molecule-1
      (ICAM3), and matrix metalloproteinase (MMP9)] showed a tendency to be elevated on
      day 7 among infants with funisitis. Adjusting for gestational age, growth
      restriction, and three postnatal exposures (ventilation on day 7, presumed and
      definite early bacteremia, and Bell stage III necrotizing endocolitis) did not
      diminish the elevated odds ratios of concentrations in the top quartile (for
      gestational age and day the specimen was obtained) of MPO, IL1beta, TNFalpha,
      IL8, ICAM3, and MMP9. The persistence of a relationship between umbilical cord
      inflammation and elevated blood concentrations of inflammation-related proteins
      on postnatal day 7 suggests the existence of phenomena that contribute to a
      reinforcement loop and thereby sustained systemic inflammation.

PMID- 21722969
TI  - Canine malignant melanoma alpha-3 integrin binding peptides.
AB  - There is a need to develop novel targeted imaging and therapeutic agents that can
      aid in early diagnosis, detection of metastasis and treatment of melanoma. Alpha
      3 integrin is overexpressed in 82% of metastatic melanomas in humans and may be a
      potential target for peptide ligands carrying therapeutic agents. Five melanoma
      cell lines were generated from canine primary oral and metastatic canine tumors,
      grown in mice, and validated with melanoma markers Melan A, S-100, Micropthalmia
      transcription factor (MITF), Tyrosinase, and MART-1. The melanoma cell lines were
      tested for binding affinity to previously published alpha-3 integrin-binding
      peptides containing the cdGXGXXc motif. Fluorescent conjugates of the alpha-3
      integrin binding OA02 peptide were used to quantify receptor affinity in the cell
      lines, a specimen of canine primary oral melanoma, and melanoma xenografts. Alpha
      3 integrin was expressed by all 5 canine melanoma cell lines. Four of the 5 lines
      as well as the primary canine tumor showed affinity to alpha-3 integrin binding
      peptides with the cdGXGXXc motif. Optical imaging of canine melanoma xenografts
      in nude mice indicates rapid, strong uptake of the optical tracer in the tumor
      with an average persistence of approximately 48 h. Ex vivo images showed high
      tumor-to-background ratio, with tumor signals more than twice that of the kidney
      and other vital organs. We propose that integrin alpha-3 integrin binding ligands
      could potentially become useful probes for imaging and delivery of cytotoxic
      agents for the treatment of melanoma.

PMID- 21722970
TI  - Ventral tegmental area-basolateral amygdala-nucleus accumbens shell
      neurocircuitry controls the expression of heroin-conditioned immunomodulation.
AB  - The present investigations sought to determine whether the ventral tegmental area
      (VTA), basolateral amygdala (BLA), and nucleus accumbens shell (NAC) comprise a
      circuitry that mediates heroin-induced conditioned immunomodulation. Rats were
      given conditioning trials in which they received an injection of heroin upon
      placement into a distinctive environment. Prior to testing, rats received
      unilateral intra-BLA microinfusion of a D(1) antagonist concomitantly with
      unilateral intra-NAC shell microinfusion of an NMDA antagonist. Disconnection of
      the VTA-BLA-NAC circuit impaired the ability of the heroin-paired environment to
      suppress lipopolysaccharide-induced immune responses, defining for the first time
      a specific neural circuit involved in conditioned neural-immune interactions.

PMID- 21722971
TI  - Structural insights into RAMP modification of secretin family G protein-coupled
      receptors: implications for drug development.
AB  - Secretin family G protein-coupled receptors (GPCRs) are important therapeutic
      targets for migraine, diabetes, bone disorders, inflammatory disorders and
      cardiovascular disease. They possess a large N-terminal extracellular domain
      (ECD) known to be the primary ligand-binding determinant. Structural
      determination of several secretin family GPCR ECDs in complex with peptide
      ligands has been achieved recently, providing insight into the molecular
      determinants of hormone binding. Some secretin family GPCRs associate with
      receptor activity-modifying proteins (RAMPs), resulting in changes to receptor
      pharmacology. Recently, the first crystal structure of a RAMP ECD in complex with
      a secretin family GPCR was solved, revealing the elegant mechanism governing
      receptor selectivity of small molecule antagonists of the calcitonin gene-related
      peptide (CGRP) receptor. Here we review the structural basis of ligand binding to
      secretin family GPCRs, concentrating on recent progress made on the structural
      basis of RAMP-modified GPCR pharmacology and its implications for rational drug
      design.

PMID- 21722972
TI  - Role of permanent atrial fibrillation (AF) on long-term mortality in community
      dwelling elderly people with and without chronic heart failure (CHF).
AB  - Permanent AF is characterized by an increased mortality in elderly subjects with
      CHF. Moreover, AF increased the risk of mortality also in elderly subjects
      without CHF. Thus, we examined long-term mortality in community-dwelling elderly
      people with and without CHF. A total of 1332 subjects aged 65 and older were
      selected from the electoral rolls of Campania, a region of southern Italy. The
      relationship between AF and mortality during a 12-year follow-up in 125 subjects
      with CHF and in 1.143 subjects without CHF were studied. Elderly subjects showed
      a higher mortality in those with respect to those without AF (72.1% vs. 51.8%;
      p<0.01). Similarly, elderly subjects without CHF showed a higher mortality in
      those with respect to those without AF (61.8% vs. 49.8%; p<0.05). In contrast,
      elderly subjects with CHF showed a similar mortality in those with respect to
      those without AF (74.7% vs. 82.4%; p=0.234). Multivariate analysis shows that AF
      was predictive of mortality in all elderly subjects (Hazard Risk=HR=1.39, 95%
      confidence interval (CI)=1.25-2.82; p<0.001). When the analysis was conducted
      considering the presence and the absence of CHF, AF was strongly predictive of
      mortality in elderly subjects without CHF (HR=1.95, 95%CI=1.25-4.51; p<0.001) but
      not in those with CHF (HR=1.12, 95%CI=0.97-3.69; p=0.321). We concluded that AF
      is able to predict long-term mortality in elderly subjects. Moreover, AF is
      strongly predictive of long-term mortality in the absence but not in the presence
      of CHF.

PMID- 21722973
TI  - Prevalence and characteristics of restless legs syndrome (RLS) in the elderly and
      the relation of serum ferritin levels with disease severity: hospital-based study
      from Istanbul, Turkey.
AB  - The RLS is an underdiagnosed condition, characterized by unpleasant sensations in
      the legs. Pathophysiological mechanisms may include iron deficiency as reflected
      by low serum ferritin levels and dopaminergic system dysfunction. The purpose of
      our study was to investigate the prevalence and characteristics of RLS in the
      elderly and the relation of serum ferritin levels with disease severity.
      Ambulatory 1012 (621 women, 391 men, mean age: 73.51 +/- 7.12 years) consecutive
      patients above 65 years who admitted to our clinic for any reason were evaluated
      according to the International RLS Study Group (IRLSSG) criteria: 103 patients
      (74 women, 29 men, mean age: 72.43 +/- 6.31) (10.18%) had RLS diagnosis. Only 9
      of them had known RLS. The duration of symptoms was 4.80 +/- 4.65 years and 27
      patients (26.2%) had positive family history. The average of serum ferritin
      levels was 39.13 +/- 23.74 ng/ml and 71 patients (68.9%) had serum ferritin
      levels <= 50 ng/ml. The disease severity was evaluated with IRLSSG rating scale.
      Patients were classified as severe-very severe group (n=49) and mild-moderate
      group (n=54). The ferritin levels of severe-very severe disease group were lower
      than those of mild-moderate disease group (26.01 +/- 15.82 ng/ml versus 49.87 +/-
      23.24 ng/ml, p<0.001). Our data show that RLS is very common in the elderly and
      the disease is more severe in patients with lower ferritin levels.

PMID- 21722974
TI  - The reliability and validity of the daily activities dependence on vision (DADV)
      scale to evaluate vision related functional limitations.
AB  - The purpose was to determine the reliability and validity of the DADV scale to
      evaluate vision-related functional limitations in persons over 65 years. Cross
      sectional study was performed to determine the reliability and validity of a
      questionnaire (9 items). A total of 1387 subjects were selected by random
      sampling. An analysis of the intra/inter-observer reliability was performed and
      the convergent validity with the Visual Function Index, 14 items (VF-14) was
      determined. The number of patients who had some difficulty in performing any of
      the activities was 223 (19.2%; 95%CI=16.9-21.5). The intraclass correlation
      coefficient (ICC) of the intra/inter-observer reliability analysis was 0.883 and
      0.900, respectively. Factorial analysis demonstrated that one single factor
      explained 63.2% of the total variance (visual function). The scale showed a high
      degree of convergent validity (ICC=0.857) with the VF-14. Visual acuity showed a
      moderate correlation with the DADV score (r=0.366). The Rasch analysis showed a
      satisfactory model fit for the items. Although the DADV scale is a short
      questionnaire it showed high correlation with the VF-14 and moderate correlation
      with visual acuity. The results indicate that the scale has acceptable
      reliability and is valid to efficiently evaluate visual function.

PMID- 21722975
TI  - The effects of head circumference (HC) and lifetime alcohol consumption (AC) on
      cognitive function in the elderly.
AB  - Smaller premorbid brain volume is known to be related to cognitive deterioration
      in older adults, supporting a reserve hypothesis of brain aging. Heavy lifetime
      alcohol consumption (AC) may also increase the risk of cognitive impairment. The
      aim of this study was to examine the effects of head circumference (HC) and
      lifetime AC on cognitive function in the elderly. This study is part of a large,
      longitudinal study of men aged 60 years or older in the Korean community. We
      studied 1569 subjects with complete demographic, anthropometric and AC data.
      Cognitive function was assessed by the Korean version of Mini Mental State
      Examination (K-MMSE). Participants reported at the time of interview their
      lifetime alcohol drinking patterns. HC was also measured. We did a cross
      sectional analysis the relation between two factors to cognitive function. After
      a multivariable adjustment, the interactive effect between HC and lifetime AC was
      shown to be significantly associated with cognitive function (F=2.55, p=0.038).
      Simple main effect analysis showed that smaller HC and a high level of lifetime
      AC were related with decreased cognitive function. All these findings suggest the
      possibility that lifetime AC and HC have synergistic effects on cognitive
      impairment.

PMID- 21722976
TI  - Risk of falls in 85-year-olds is associated with functional and cognitive status:
      the Octabaix Study.
AB  - Falls are a source of morbidity and mortality in the oldest old. The purpose of
      this study was to describe the prevalence of falls among community-dwelling 85
      year-olds and to study the factors associated with falling. A cross-sectional
      study, including geriatric assessment, was conducted within the framework of the
      Octabaix Study. Functional status was measured with Barthel Index (BI) and Lawton
      Index (LI), cognitive impairment was assessed with the Mini-Mental State
      Examination (MMSE), the Spanish version of which is called MEC, Comorbidity by
      Charlson Index (CCI), and data were gathered on nutritional risk, social risk,
      falls, and drugs. The fall prevalence among the 328 octogenarians studied was
      28.4%. A bivariate analysis revealed an association with being female (p=0.017)
      and poorer functional status according to BI (p=0.027). Logistic analysis showed
      an association with female gender (OR=1.96; 95%CI=1.15-3.33; p=0.014), BI
      (OR=0.98; 95%CI=0.97-0.99; p=0.007) and MEC (OR=1.05; 95%CI=1.01-1.09; p=0.027).
      The prevalence of falls among 85-year-olds is high and similar to that described
      in those aged 65 or over. The analyses show that being female, a degree of
      disability and a good score on cognitive status were independent risk factors for
      falls among these community-dwelling.

PMID- 21722977
TI  - Establishing novel prostacyclin-synthesizing cells with therapeutic potential
      against heart diseases.
AB  - BACKGROUND: For decades, there have been many ongoing attempts to use
      prostaglandin I(2) (PGI(2)) to treat heart diseases, such as pulmonary arterial
      hypertension. However, the short half life of PGI(2) has limited the therapeutic
      impact potential. METHODS: Here, we have engineered a novel adipose tissue
      derived cell that constantly produces PGI(2,) through transfecting of an
      engineered cDNA of a hybrid enzyme (human COX-1-10-aa-PGIS) which has superior
      triple catalytic functions in directly converting arachidonic acid into PGI(2).
      RESULTS: The gene-transfected cells were further converted into a stable cell
      line, in which cells constantly express the hybrid enzyme and are capable of
      producing large-amounts of PGI(2). In a comparison between un-transfected- and
      gene-transfected cells, it was determined that the majority of the endogenous AA
      metabolism shifted from that of unwanted PGE(2) (in un-transfected cells) to that
      of the preferred PGI(2) (in gene-transfected cells) with a PGI(2)/PGE(2) ratio
      change from 0.03 to 25. The PGI(2)-producing cell line not only exhibited an
      approximate 50-fold increase in PGI(2) biosynthesis, but also demonstrated
      superior anti-platelet aggregation in vitro, and increased reperfusion in the
      mouse ischemic hindlimb model in vivo. CONCLUSIONS: The cells, which have an
      ability to increase the biosynthesis of the vascular protector, PGI(2), while
      reducing that of the vascular inflammatory mediator, PGE(2), provide a dual
      effect on vascular protection, which is not available through any existing drug
      treatments. Thus, the current finding has potential to be an experimental
      intervention for PGI(2)-deficient heart diseases, such as pulmonary arterial
      hypertension.

PMID- 21722978
TI  - Analysis and classification of heart sounds with mechanical prosthetic heart
      valves based on Hilbert-Huang transform.

PMID- 21722979
TI  - Improved cardiac survival, freedom from MACE and angina-related quality of life
      after successful percutaneous recanalization of coronary artery chronic total
      occlusions.
AB  - BACKGROUND: Most percutaneous recanalizations of coronary artery chronic total
      occlusion (CTO) are not attempted because of the skepticism on their long-term
      clinical benefit. We assessed the effect of percutaneous CTO recanalization
      procedures on long-term cardiac survival, freedom from MACE and angina-related
      quality of life (AQL). METHODS: All consecutive patients who underwent attempt of
      percutaneous native coronary artery CTO recanalization between 2003 and 2009 were
      included in the study. MACE was defined as combined cardiac death, myocardial
      infarction (MI) and target vessel revascularization (TVR). AQL was assessed by
      the Seattle Angina Questionnaire-UK-version (SAQ-UK). RESULTS: Among 302 patients
      who received an attempt of percutaneous CTO recanalization, 237 (78%) had a
      successful procedure while in 65 (22%) the procedure failed. Overall intra
      hospital complication rate was 3.0%, with no difference between the two groups.
      Median follow-up was 4.0 years, during which 13 patients had a fatal cardiac
      event. Patients in whom the CTO recanalization procedure failed had a higher risk
      of cardiac death (HR 3.39; 95% CI 1.14-10.1;p=0.03; after propensity score
      adjustment, HR 2.83; 95% CI 0.89-8.96;p=0.07) and MACE (HR 5.40; 95% CI 2.71
      10.5;p<0.001; adjusted HR 3.34; 95% CI 1.47-7.58;p=0.003) compared to patients
      with successful procedure. CTO recanalization significantly improved the AQL
      during follow-up: patients with successful procedure experienced less physical
      activity limitation (p=0.01), rarer angina episodes (p<0.001) and greater
      treatment satisfaction (p=0.03) compared to patients with failed procedure.
      CONCLUSIONS: Patients with successful CTO recanalization had a trend towards
      better cardiac survival and significant lower risk of MACE and improvement of AQL
      compared to patients with failed procedures.

PMID- 21722980
TI  - Quality assurance for prospective EORTC radiation oncology trials: the challenges
      of advanced technology in a multicenter international setting.
AB  - The European Organization for the Research and Treatment of Cancer (EORTC) is a
      pan-European structure charged with improving cancer treatment through the
      testing of new therapeutic strategies in phases I-III clinical studies. Properly
      conducted trials in radiation oncology are required to demonstrate superiority of
      a new treatment over the current standard. The Radiation Oncology Group (ROG) has
      initiated a complex quality assurance (QA) program to ensure safe and effective
      treatment delivery. Most modern trials are multicenter and multidisciplinary,
      further increasing the importance of early, strict and consistent QA in
      radiotherapy (RT). QART measures confirm whether a site possesses minimum staff
      and equipment for participation. Dummy runs, reviews of patient treatment plans
      and complex dosimetry checks verify the ability of an institution to comply with
      the protocol. Data required for evaluation are increasingly exchanged digitally,
      allowing detailed plan reconstruction, evaluation of target volume delineation
      and recalculation of dose-volume parameters for comparison against predefined
      standards. The five tiers of QA implemented in EORTC trials are reviewed, along
      with past, current and future QART initiatives. As substantial human and
      financial resources are increasingly invested in QART, the importance of cost
      benefit analysis of QA and its impact on clinical outcome cannot be overstated.

PMID- 21722981
TI  - New insights into the molecular pathology of radiation-induced pneumopathy.
AB  - BACKGROUND AND PURPOSE: Pneumonitis and fibrosis constitute dose-limiting side
      effects of thorax or total body irradiation. An improved understanding of the
      underlying mechanisms is a prerequisite for the development of effective
      radioprotective strategies. Here we characterized the behavior of resident and
      immune cells in a murine model of radiation-induced pneumopathy. MATERIALS AND
      METHODS: Wild type (WT) or RAG-2 deficient C57BL/6 mice received 15 Gray of
      (hemi)-thorax irradiation in a single dose. Bronchoalveolar lavage fluid (BALF)
      and lung tissue were collected at defined time points post-irradiation for the
      determination of apoptosis, microvascular injury, and histological and
      immunohistochemical analyses. RESULTS: Higher albumin levels and increased
      apoptosis were detected in the BALF 21 days after irradiation, indicative for
      delayed damage to resident cells. Irradiation also induced time-dependent changes
      in the BALF cytokine profile, the recruitment of activated T-cells into the lung
      and the formation of lipid-loaded resident cells. Lung fibrosis occurred earlier
      in RAG-2(-/-) mice, which lack mature T and B cells, compared to WT mice.
      CONCLUSIONS: Thorax irradiation triggers a delayed disturbance of tissue
      integrity and lipid metabolism in the lung. Activated T-lymphocytes infiltrating
      the lung tissue upon thorax irradiation participate in the protection of the lung
      from radiation-induced fibrosis.

PMID- 21722982
TI  - Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to chemotherapy
      through regulation of UBE2T.
AB  - BACKGROUND AND PURPOSE: Hypoxia is a common feature of the microenvironment of
      solid tumors which has been shown to promote malignancy and poor patient outcome
      through multiple mechanisms. The association of hypoxia with more aggressive
      disease may be due in part to recently identified links between hypoxia and
      genetic instability. For example, hypoxia has been demonstrated to impede DNA
      repair by down-regulating the homologous recombination protein RAD51. Here we
      investigated hypoxic regulation of UBE2T, a ubiquitin ligase required in the
      Fanconi anemia (FA) DNA repair pathway. MATERIALS AND METHODS: We analysed UBE2T
      expression by microarray, quantitative PCR and western blot analysis in a panel
      of cancer cell lines as a function of oxygen concentration. The importance of
      this regulation was assessed by measuring cell survival in response to DNA
      damaging agents under normoxia or hypoxia. Finally, HIF dependency was determined
      using knockdown cell lines and RCC4 cells which constitutively express HIF1alpha.
      RESULTS: Hypoxia results in rapid and potent reductions in mRNA levels of UBE2T
      in a panel of cancer cell lines. Reduced UBE2T mRNA expression is HIF independent
      and was not due to changes in mRNA or protein stability, but rather reflected
      reduced promoter activity. Exposure of tumor cells to hypoxia greatly increased
      their sensitivity to treatment with the interstrand crosslinking (ICL) agent
      mitomycin C. CONCLUSIONS: Exposure to hypoxic conditions down-regulates UBE2T
      expression which correlates with an increased sensitivity to crosslinking agents
      consistent with a defective Fanconi anemia pathway. This pathway can potentially
      be exploited to target hypoxic cells in tumors.

PMID- 21722983
TI  - The amount of DNA damage needed to activate the radiation-induced G2 checkpoint
      varies between single cells.
AB  - BACKGROUND AND PURPOSE: The radiation-induced G2 checkpoint helps facilitate DNA
      repair before cell division. However, recent work has revealed that human cells
      often escape the G2 checkpoint with unrepaired DNA breaks. The purpose was to
      explore whether G2 checkpoint activation occurs according to a threshold level of
      DNA damage. MATERIALS AND METHODS: G2 checkpoint activation was assayed at 75-90
      min and 24-48 h after X-ray irradiation of BJ diploid fibroblasts and U2OS
      osteosarcoma cells. Multiparameter flow cytometry with pacific blue barcoding,
      and flow cytometry-based sorting of phospho-H3 positive cells to microscope
      slides, were used to examine the DNA damage marker gamma-H2AX in individual
      mitotic cells that had escaped the G2 checkpoint. RESULTS: For all radiation
      doses and times tested, the number of gamma-H2AX foci varied between individual
      mitotic cells. At 75 min the median levels of gamma-H2AX in mitotic cells
      increased with higher radiation doses. At 24-48 h, following a prolonged G2
      checkpoint, cells were more resistant to checkpoint re-activation by a second
      dose of radiation. CONCLUSION: Our results suggest that different amounts of DNA
      damage are needed to activate the G2 checkpoint in individual cells. Such single
      cell variation in checkpoint activation may potentially contribute to radiation
      induced genomic instability.

PMID- 21722984
TI  - Treatment of small cell lung cancer with TRA-8 in combination with cisplatin and
      radiation.
AB  - BACKGROUND: Limited stage small cell lung cancer (SCLC) represents a minority of
      SCLC. Despite extensive clinical trials, standard treatment remains cisplatin
      based chemotherapy and thoracic irradiation (TI). This study focused on the
      interaction of cisplatin/radiation with the anti-human DR5 monoclonal antibody
      TRA-8 in SCLC cells. TRA-8 binds specifically to DR5 and has been shown to
      activate apoptosis. METHODS: Four human SCLC cell lines were utilized for
      experimentation (SCLC-41, SCLC-58, SCLC-68, and SCLC-74). Immunoblot analysis was
      used to determine relative protein levels of DR5, DR4 and pro-caspase 8 for each
      cell line. Using a tetrazolium-based assay (XTT), the IC(50) values for cisplatin
      with or without TRA-8 were determined for the SCLC cell lines. Four SCLC lines
      were assayed with a combination of TRA-8 (10 MUg/ml), 2 Gy radiation and various
      concentrations of cisplatin. Apoptosis was evaluated using Annexin V-FITC and
      cleaved caspase immunoblotting. Using a SCLC-58 subcutaneous xenograft model,
      treatment began 21 d after tumor cell injection. Treatment included weekly
      cisplatin (4 mg/kg) and radiation of 1 Gy (24 h after cisplatin) and TRA-8 (200
      MUg) was administered i.p. twice weekly for three weeks. RESULTS: Immunoblot
      analysis showed similar levels of DR5 for all cell lines with variable levels of
      DR4. Various concentrations of TRA-8 antibody (<= 10 MUg/ml) induced no
      significant cytotoxicity in the SCLC cell lines. The in vitro combination
      treatment with TRA-8 (10 MUg/ml), 1.25 MUg/ml cisplatin and 2 Gy radiation showed
      increased cytotoxicity when compared to combinations without TRA-8. Furthermore,
      the triple combination demonstrated the greatest amount of apoptosis as measured
      by Annexin V staining. The in vivo studies showed the combination of 1G y,
      cisplatin and TRA-8 extended the tumor doubling time to 44 d as compared to any
      doublet treatment groups that ranged from 12 to 20 d. Analysis of survival data
      showed 100% of the combination group (RT+cisplatin+TRA-8) were alive 65 d after
      treatment began whereas all doublet treatment groups showed 50% or less survival.
      CONCLUSIONS: These studies showed increased cytotoxicity when TRA-8 was added to
      radiation/cisplatin in SCLC. This effect was demonstrated in vitro and in vivo.
      TRA-8 represents a promising new agent in the treatment of SCLC.

PMID- 21722985
TI  - Assessing 'radiosensitivity' with kinetic profiles of gamma-H2AX, 53BP1 and BRCA1
      foci.
AB  - BACKGROUND AND PURPOSE: DNA repair assays to identify radiosensitive patients
      have had limited clinical implementation due to long turn-around times or limited
      specificity. This study evaluates gamma-H2AX-Irradiation Induced Foci (IRIF)
      kinetics as a more rapid surrogate for the 'gold standard' colony survival assay
      (CSA) using several known DNA repair disorders as reference models. MATERIALS AND
      METHODS: Radiosensitive cells of known and unknown etiology were studied. gamma
      H2AX-IRIFs were quantified over 24 h, and the curves were fitted by combining
      logarithmic growth and exponential decay functions. Fitted values that differed
      from radionormal controls were considered aberrant and compared to CSA results.
      RESULTS: We observed 87% agreement of IRIF data with the CSA for the 14 samples
      tested. Analysis of gamma-H2AX-IRIF kinetics for known repair disorders indicated
      similarities between an RNF168(-/-) cell line and an RS cell of unknown etiology.
      These cell lines were further characterized by a reduction in BRCA1-IRIF
      formation and G2/M checkpoint activation. CONCLUSIONS: gamma-H2AX-IRIF kinetics
      showed high concordance with the CSA in RS populations demonstrating its
      potential as a more rapid surrogate assay. This method provides a means to
      globally identify defective DNA repair pathways in RS cells of unknown etiology
      through comparison with known DNA repair defects.

PMID- 21722986
TI  - Autophagy contributes to resistance of tumor cells to ionizing radiation.
AB  - BACKGROUND AND PURPOSE: Autophagy signaling is a novel important target to
      improve anticancer therapy. To study the role of autophagy on resistance of tumor
      cells to ionizing radiation (IR), breast cancer cell lines differing in their
      intrinsic radiosensitivity were used. MATERIALS AND METHODS: Breast cancer cell
      lines MDA-MB-231 and HBL-100 were examined with respect to clonogenic cell
      survival and induction of autophagy after radiation exposure and pharmacological
      interference of the autophagic process. As marker for autophagy the appearance of
      LC3-I and LC3-II proteins was analyzed by SDS-PAGE and Western blotting.
      Formation of autophagic vacuoles was monitored by immunofluorescence staining of
      LC3. RESULTS: LC3-I and LC3-II formation differs markedly in radioresistant MDA
      MB-231 versus radiosensitive HBL-100 cells. Western blot analyses of LC3-II/LC3-I
      ratio indicated marked induction of autophagy by IR in radioresistant MDA-MB-231
      cells, but not in radiosensitive HBL-100 cells. Indirect immunofluorescence
      analysis of LC3-II positive vacuoles confirmed this differential effect. Pre
      treatment with 3-methyladenine (3-MA) antagonized IR-induced autophagy. Likewise,
      pretreatment of radioresistant MDA-231 cells with autophagy inhibitors 3-MA or
      chloroquine (CQ) significantly reduced clonogenic survival of irradiated cells.
      CONCLUSION: Our data clearly indicate that radioresistant breast tumor cells show
      a strong post-irradiation induction of autophagy, which thus serves as a
      protective and pro-survival mechanism in radioresistance.

PMID- 21722987
TI  - The complex analytical landscape of gene flow inference.
AB  - Gene flow estimation is essential for characterizing local adaptation, speciation
      potential and connectivity among threatened populations. New model-based
      population genetic methods can resolve complex demographic histories, but many
      studies in fields such as landscape genetics continue to rely on simple rules of
      thumb focused on gene flow to explain patterns of spatial differentiation. Here,
      we show how methods that use gene genealogies can reveal cryptic demographic
      histories and provide better estimates of gene flow with other parameters that
      contribute to genetic variation across landscapes and seascapes. We advocate for
      the expanded use and development of methods that consider spatial differentiation
      as the product of multiple forces interacting over time, and caution against a
      routine reliance on post-hoc gene flow interpretations.

PMID- 21722988
TI  - [Retinal lesions in pseudoxanthoma elasticum: 51 patients].
AB  - OBJECTIVE: Description of retinal lesions in patients with pseudoxanthoma
      elasticum (PXE). PATIENTS AND METHODS: This cross sectional study evaluated 51
      consecutive patients (31 women and 20 men, mean age, 47 years+/-16) from June
      2008 to September 2010. Clinical and fundoscopic evaluations were performed for
      each patient with fundus images: colour, red-free, autofluorescence of the
      central retina, and red-free of the retinal periphery. Several patients were
      examined with fluorescein angiography, indocyanine green angiography, or optical
      coherence tomography when neovascular complications were suspected. RESULTS: In
      addition to classical angioid streaks and "peau d'orange" aspects, we identified
      several other retinal lesions: pattern dystrophy, drusen of the optic nerve,
      peripheral "comet tail" lesions, subretinal fibrosis, and autofluorescent
      perimacular white spots, suggesting atrophy of the pigmented epithelium overlying
      the "peau d'orange" lesions, which appeared earlier, with onset subsequently
      followed by angioid streaks. The incidence of "peau d'orange" decreased with age.
      Subretinal fibrosis and pattern dystrophy of the macula were often associated and
      occurred around 40 years of age. The risk of neovascular complications increased
      with age. CONCLUSION: Macular decompensation most often occurring around the age
      of 50 is a common event in PXE, associated with aging, disappearance of "peau
      d'orange", changes in angioid streaks, and development of atrophy of the retinal
      pigment epithelium.

PMID- 21722989
TI  - Quality of life in dermatomyositis.
AB  - BACKGROUND: Quality of life (QoL) for patients with inflammatory skin disease can
      be significant, but has been evaluated in just one study in dermatomyositis (DM).
      OBJECTIVE: We sought to examine the relationship between the Cutaneous
      Dermatomyositis Area (CDASI) and Severity Index, a DM-specific cutaneous severity
      instrument, and various QoL study instruments and to determine the impact of DM
      on QoL. METHODS: Skin-specific QoL instruments, the Skindex and the Dermatology
      Life Quality Index, and global medical QoL instruments, the Short Form 36 and the
      Health Assessment Questionnaire-Disability Index, were used. Pruritus was
      evaluated by a visual analog scale and a 0-to-10 scale in DM and cutaneous lupus
      erythematosus (CLE) populations, respectively. RESULTS: There was a significant
      correlation between the CDASI and all skin-specific QoL scores (lowest P =
      .0377). Using the Short Form 36, DM population was found to have significantly
      worse QoL scores than the general population with the exception of bodily pain
      (all subscore P values < .01). Furthermore, DM had a significantly lower vitality
      score, representing energy level, compared with CLE, hypertension, diabetes, and
      recent myocardial infarction scores (lowest P = .003). There was a significantly
      lower mental health score, representing overall mood, to all compared diseases
      except CLE and clinical depression (P values < .01 when significant). We found
      that DM produces more pruritus than CLE (P < .0001). LIMITATIONS: A larger
      patient population needs to be studied to further assess QoL in patients with DM.
      CONCLUSION: We conclude that DM has a large impact on QoL, even when compared
      with other diseases, and that DM skin disease activity correlates with a poorer
      QoL.

PMID- 21722990
TI  - Control of an outbreak of carbapenem-resistant Pseudomonas aeruginosa in a
      haemato-oncology unit.
AB  - An outbreak of a multidrug-resistant Pseudomonas aeruginosa producing metallo
      beta-lactamase (MBLPA) in a haemato-oncology unit was controlled using
      multidisciplinary interventions. The present study assesses the effects of these
      interventions by active surveillance of the incidence of MBLPA infection at the
      1,240-bed tertiary care Kyoto University Hospital in Kyoto, Japan. Infection
      control strategies in 2004 included strengthening contact precautions, analysis
      of risk factors for MBLPA infection and cessation of urine collection. However,
      new MBLPA infections were identified in 2006, which prompted enhanced
      environmental cleaning, routine active surveillance, and restricting carbapenem
      usage. Between 2004 and 2010, 17 patients in the unit became infected with
      indistinguishable MBLPA strains. The final five infected patients were found by
      routine active surveillance, but horizontal transmission was undetectable. The
      MBLPA outbreak in the haemato-oncology unit was finally contained in 2008.

PMID- 21722991
TI  - [Introduction of a management system in intensive care medicine based on the
      safety of the seriously ill patient during the entire hospitalization process:
      extended intensive care medicine].
AB  - The clinical care of hospitalized seriously ill patients must be suitably
      proportionate independently of the functional unit to which they have been
      admitted. Most of these patients are admitted to the Intensive Care Unit (ICU),
      where uninterrupted management is provided, with important technological and care
      resources. However, hospitalization of the seriously ill patient must be
      understood as a continuum starting and ending beyond hospital stay. Anticipating
      critical worsening requiring admission to the ICU would be of benefit to the
      patient, avoiding greater clinical worsening, and also would be of benefit to the
      hospital, by allowing improved resource management. Intensivists are the
      professionals best suited for this purpose, since they are trained to recognize
      the seriousness of an always dynamic clinical situation. Addressing this task
      implies a change in the traditional way of working of the ICU, since a critical
      patient is not only a patient already admitted to the Unit but also any other
      patient admitted to hospital whose clinical situation is becoming destabilized.
      In this context, our ICU has established two strategic lines. One consists of the
      identification of patients at risk outside the Unit and is based on the
      recognition, diagnostic orientation and early treatment of the seriously ill
      patient, in collaboration with other clinical specialties and independently of
      the hospital area to which the patient has been admitted. The second line in turn
      comprises clinical care within the actual Unit, and is based on the promotion of
      safety and the vigilance of nosocomial infections.

PMID- 21722992
TI  - [Noninvasive ventilation in pneumonia due to N1H1 virus].

PMID- 21722993
TI  - [Community clinical trial on type 2 diabetics: Benefits of health education
      associated with physical exercise].

PMID- 21722994
TI  - [Health care pressure and redistribution of tasks: an opportunity to improve
      primary care].

PMID- 21722995
TI  - Is a selective brain (18)F-FDG PET/CT study profitable in patients with small
      cell lung cancer?
AB  - AIM: To evaluate the diagnostic yield of a selective brain (18)F-FDG PET/CT in
      neurologically asymptomatic patients with small cell lung cancer. MATERIAL AND
      METHODS: Twenty-one neurologically asymptomatic patients referred to our service
      between July 2008 and December 2009 for staging of small cell lung cancer were
      included in the study. All underwent a standard (18)F-FDG PET/CT study followed
      by a selective brain PET/CT. The neurological findings were confirmed by CT scan
      with intravenous contrast, MRI or minimum clinical follow-up of 6 months. The
      brain PET/CT was considered positive if any alteration was observed in the FDG
      distribution that was not related with previously known benign lesion in the CT
      image. RESULTS: Brain metastases were detected in 5 of the 21 patients (23.8%),
      these being correctly classified in 3 of them by the selective brain PET/CT. The
      stage was upgraded in one of them with the selective brain study. Only one
      patient showed a hypermetabolic lesion in the PET images in relationship to the
      lesions observed in the CT images. Sensibility, specificity, positive predictive
      value and negative predictive value were 60, 100, 100 and 88.89%, respectively.
      CONCLUSION: Hypometabolic areas in the cerebral parenchyma are frequently
      associated to metastatic lesions in patients with small cell lung cancer. The
      selective brain PET/CT in these patients allows correct staging and early
      treatment of unsuspected metastasis.

PMID- 21722996
TI  - SPECT-CT imaging of poliostotic fibrous dysplasia.

PMID- 21722997
TI  - [Prevalence of HIV infection in an asymptomatic immigrant population].

PMID- 21722998
TI  - [Development of subcutaneous nodules after mesotherapy].

PMID- 21722999
TI  - [Gene expression profiling in the first twelve weeks of treatment in chronic
      hepatitis C patients].
AB  - INTRODUCTION: Gene expression profiling in the first weeks of treatment of
      patients with chronic hepatitis C may contribute to better evaluate the response
      to interferon-based therapy. The objective of this study was to evaluate the gene
      expression profiles of early responders and non-responders before, and after 12
      weeks of treatment with peginterferon alfa and ribavirin. METHODS: Gene
      expression profiles were analysed in 12 patients with chronic hepatitis C, and
      scheduled for treatment with peginterferon alpha and ribavirin. RESULTS: Of the
      12 patients studied, six showed a complete early virological response, while six
      failed to control viremia. In early responders, treatment with peginterferon and
      ribavirin induced an increased expression of a larger number of interferon
      induced genes (ISG15, IFI6, IFI44L, IFI27, MX1, OASL, IRF7, IFIT3, IFITM1,
      EIF2AK2, HERC5 and APOBEC3) than in non-responders (ISG15, IFI44L, IFI27, IRF7,
      USP18) in the first twelve weeks of treatment (P<0.05). In both groups, there
      were changes in the levels of certain genes poorly described in the treatment of
      hepatitis C so far. CONCLUSIONS: The gene expression profiles described in this
      study provide a new insight to understanding the pathogenesis of the disease and
      treatment effect. The more marked effect of the treatment on the expression of
      interferon-response genes observed in early responders could explain their better
      control of viral load.

PMID- 21723000
TI  - [Patient characteristics and health care burden during the influenza A (H1N1)
      2009 pandemic in the university Hospital Vall d'Hebron of Barcelona].
AB  - BACKGROUND AND OBJECTIVE: The influenza A (H1N1) 2009 pandemic initially had a
      mild impact in Catalonian hospitals, but in the autumn there was an important
      pandemic wave. We describe the main characteristics of patients seen in the Vall
      d'Hebron University Hospital in Barcelona (HUVH) during this pandemic, the risk
      factors associated with hospitalization and the health-care burden generated.
      MATERIAL AND METHOD: We included all cases of influenza A (H1N1) 2009 with
      laboratory confirmation seen in the HUVH from July 2, 2009 to January 22, 2010.
      We performed a descriptive analysis of the cases and a multivariate analysis to
      identify variables associated with the risk of hospitalization. RESULTS: The
      diagnosis was confirmed in 741 patients; 56.8% were under 16 years, while only
      2.8% were 65 and over. Thirty three per cent of children had no risk factor for
      complications, whereas in adults it was 45%. One hundred and ninety cases were
      hospitalized, 26 of them in the intensive care unit (ICU) with 5 deaths. The
      factors associated with risk of hospitalization were, age less than one year,
      immunodeficiency, and neuromuscular disease in children; and chronic lung disease
      in adults. The diagnosis of pneumonia in the emergency department was an
      important predictor of hospitalization in both children and adults. The maximum
      caseload was recorded on November 19, with 43 hospital admissions, 6 of them in
      the ICU. CONCLUSIONS: Between July and September 2009 the pandemic had a low
      impact on hospital resources, but in autumn there was a marked increase in
      emergency department visits and hospitalizations. Children had higher rates of
      confirmed cases, while adults had higher rates of hospitalizations. The risk of
      hospitalization was higher in patients with certain conditions especially in
      those with pneumonia. The pandemic wave was a moderate work load for HUVH, since
      it did not involve any modification of the usual health care programs.

PMID- 21723001
TI  - Changes in the epidemiology of tuberculosis: the influence of international
      migration flows.
AB  - INTRODUCTION: The epidemiological characteristics of patients with tuberculosis
      (TB) in European hospitals have changed in recent years. METHODS: A prospective
      study of patients with culture-proven pulmonary TB admitted to our institution
      from 1997 to 2008 is shown. RESULTS: We analyzed 661 patients with pulmonary TB.
      An increase in the incidence of TB was confirmed during the study period
      (P<.001). The proportion of patients with HIV infection decreased from 26% during
      1997-2000 to 12% during 2005-2008. However, the proportions of older (>40 years
      old) and foreign-born patients increased significantly, from 37% to 59% and from
      12% to 35%, respectively. Multivariate analysis confirmed previous
      antituberculous therapy and immigration as factors associated with resistance to
      isoniazid and to isoniazid+rifampin. After the year 2000, mortality was
      independently associated with extrapulmonary TB (OR: 3.1; CI 95%: 1.4-7.2),
      hepatitis C virus infection (OR: 6.0; CI 95%: 2.2-16.3), and diabetes (OR: 6.4;
      CI 95%: 2.4-16.8). CONCLUSION: Immigration from countries with high rates of TB
      infection has replaced HIV infection as the most relevant risk factor associated
      with TB. The increase in the number of older patients with TB and the presence of
      specific comorbid conditions, especially chronic liver dysfunction, could explain
      the more difficult management and increased mortality.

PMID- 21723002
TI  - [Marjolin's ulcer in a patient with residual Hansen's disease].

PMID- 21723003
TI  - [Severe Jarisch-Herxheimer reaction in tick-borne relapsing fever].

PMID- 21723004
TI  - Efficacy and safety of outpatient parenteral antibiotic therapy for infective
      endocarditis: a ten-year prospective study.
AB  - BACKGROUND: The length of treatment of infective endocarditis (IE) with
      parenteral antibiotics varies from 2 to 6 weeks. Although several studies
      indicate that outpatient parenteral antibiotic treatment (OPAT) could be safe for
      uncomplicated viridans-group streptococci (VGS) IE, the experience in Spain is
      limited and data on other types of endocarditis and OPAT are scarce worldwide.
      METHODS: Prospective single center study of a cohort including all patients with
      IE admitted to the Hospital Clinic of Barcelona OPAT program from January 1997 to
      December 2006. RESULTS: During the study period, 392 consecutive episodes of IE
      in non-drug abusers were attended to. Of these, 73 episodes (42 native-valve, 23
      prosthetic-valve, and 8 pacemaker-lead) were admitted to the OPAT program (19%).
      The percentage of inclusion was higher for viridans group streptococci (VGS) or
      Streptococcus bovis (S. bovis) IE (32% of all VGS or S. bovis IE episodes
      diagnosed vs. 14% of the remaining etiologies, P<.001). Twelve patients (16%)
      were readmitted due to complications, of which 3 died (4%). Glycopeptides use was
      the only predictor factor of hospital readmission (OR 4.5, 95% confidence
      interval 1.2; 16.8, P=.026). No differences in OPAT outcome were found between
      VGS plus S. bovis IE and Staphylococcus aureus (S. aureus) plus coagulase
      negative staphylococci IE. Patients spent a median of 17 day on OPAT
      (interquartile range 11-26.5), which enabled 1,466 days of hospital stay to be
      saved. CONCLUSIONS: These data suggest that OPAT for IE may be a safe and
      effective therapeutic approach in the treatment of selected patients with types
      of endocarditis other than uncomplicated VGS or S. bovis endocarditis, although
      patients taking glycopeptides need close clinical OPAT monitoring.

PMID- 21723005
TI  - [Detection by polymerase chain reaction of Rickettsia sibirica mongolotimonae in
      the skin biopsy of a rash: a case report].

PMID- 21723006
TI  - [Energy audit: a management tool in health centers].
AB  - OBJECTIVE: The aim of this study was to evaluate the viability of energy audit as
      a management tool in primary care to improve the energy efficiency and
      environmental performance of a health center by reducing its operating costs.
      METHOD: We conducted 55 energy audits in health centers from 2005-2010. The
      health centers were sized between 500 and 3,500 m(2), were located in health
      areas with 3,500 to 25,000 users, and were built between 1985 and 2007. RESULTS:
      With an average investment of 11,601 ? per site, energy consumption can be
      reduced by 10,801 kWh per year, saving 2,961 ? with a mean payback period of 3.92
      years, and preventing emission of 7,010 kg of CO(2). CONCLUSIONS: Energy auditing
      is a practical tool to reduce the operating and maintenance costs of health
      centers and of improving the comfort of the facilities.

PMID- 21723007
TI  - [Inflammatory edema of the hand].

PMID- 21723008
TI  - [Humeral lesion].

PMID- 21723009
TI  - [N-methyl-d-aspartate receptor antibody encephalitis: a treatable disorder
      involving B-lymphocytes. A report of two patients].
AB  - INTRODUCTION: N-methyl-D-aspartate receptor antibody (anti-NMDA-r AB)
      encephalitis has been recently identified. We report two cases illustrating the
      clinical features, response to immunomodulatory treatment and involvement of B
      lymphocytes that characterizes this disorder. CASE REPORTS: These patients
      illustrated the classic clinical features of anti-NMDA-r AB encephalitis
      including occurrence in young female, presence of severe neurological and
      psychiatric manifestations with confusion, seizures, mutism, hypovigilence and
      involuntary movements, and inflammatory cerebrospinal fluid. Both patients
      improved after immunotherapy. In case 1, the encephalitis was associated with an
      ovarian teratoma containing neuronal elements. In case 2, there was no tumor
      identified. A brain biopsy showed prominent perivascular B-cells infiltrates with
      some T-cells distributed in the brain parenchyma. CONCLUSION: Anti-NMDA-r AB
      encephalitis is certainly not rare and needs to be promptly recognized and
      treated. An associated neoplasia is inconstant and the pathophysiology involves
      humoral immunity.

PMID- 21723010
TI  - Nutritional screening and mortality in newly institutionalised elderly: a
      comparison between the geriatric nutritional risk index and the mini nutritional
      assessment.
AB  - BACKGROUND & AIMS: Several tools are available for nutritional screening. We
      evaluated the risk of mortality associated with the Geriatric Nutritional Risk
      Index (GNRI) and the Mini Nutritional Assessment (MNA) in newly institutionalised
      elderly. METHODS: A prospective observational study involving 358 elderly newly
      admitted to a long-term care setting. Hazard ratios (HR) for mortality among GNRI
      categories and MNA classes were estimated by multivariable Cox's model. RESULTS:
      At baseline, 32.4% and 37.4% of the patients were classified as being
      malnourished (MNA <17) and at severe nutritional risk (GNRI <92), respectively,
      whereas 57.5% and 35.2%, respectively, were classified as being at risk for
      malnutrition (MNA 17-23.5) and having low nutritional risk (GNRI 92-98). During a
      median follow-up of 6.5 years [25th-75th percentile, 5.9-8.6], 297 elderly died.
      Risk for all-cause mortality was significantly associated with nutritional risk
      by the GNRI tool (GNRI<92 HR = 1.99 [95%CI, 1.38-2.88]; GNRI 92-98 HR = 1.51
      [95%CI, 1.04-2.18]) but not with nutritional status by the MNA. A significant
      association was also found with cardiovascular mortality (GNRI <92 HR = 1.79
      [95%CI, 1.23-2.61]). CONCLUSIONS: Nutritional risk by GNRI but not nutritional
      status by MNA was associated with higher mortality risk. Present data suggest
      that in the nutritional screening of newly institutionalised elderly the use of
      the GNRI should be preferred to that of the MNA.

PMID- 21723011
TI  - Diagnostic accuracy of fat-saturated T2-weighted magnetic resonance imaging in
      the diagnosis of perforation of the articular disc of the temporomandibular
      joint.
AB  - The accuracy of diagnosing a perforation of the articular disc of the
      temporomandibular joint (TMJ) is poor with conventional magnetic resonance
      imaging (MRI). We recently reported that a high signal-intensity area is usually
      found on fat-saturated T2-weighted MRI in the joint space between the articular
      disc and cartilage surface in joints in which the disc is displaced. A discrete
      image with an area of high signal-intensity in the middle of the articular disc
      may indicate perforation or rupture. The purpose of this study was to compare the
      accuracy of diagnosis of a perforated articular disc by fat-saturated T2-weighted
      MRI with that of arthroscopy. We studied 50 joints in 50 patients with closed
      lock of the TMJ who were examined with MRI and then by arthroscopy using an ultra
      thin arthroscope. The agreement between the two methods of diagnosis was assessed
      using the kappa coefficient. Evidence of perforation of the disc on MRI and
      arthroscopically was found in the same 7 joints; there was complete concordance
      (kappa=1.00, p<0.001). The accuracy of diagnosis of perforation of a disc by fat
      saturated MRI was therefore the same as that by arthroscopy using an ultra-thin
      arthroscope.

PMID- 21723012
TI  - The effect of ankle foot orthosis stiffness on the energy cost of walking: a
      simulation study.
AB  - BACKGROUND: In stroke and multiple sclerosis patients, gait is frequently
      hampered by a reduced ability to push-off with the ankle caused by weakness of
      the plantar-flexor muscles. To enhance ankle push-off and to decrease the high
      energy cost of walking, spring-like carbon-composite Ankle Foot Orthoses are
      frequently prescribed. However, it is unknown what Ankle Foot Orthoses stiffness
      should be used to obtain the most efficient gait. The aim of this simulation
      study was to gain insights into the effect of variation in Ankle Foot Orthosis
      stiffness on the amount of energy stored in the Ankle Foot Orthosis and the
      energy cost of walking. METHODS: We developed a two-dimensional forward-dynamic
      walking model with a passive spring at the ankle representing the Ankle Foot
      Orthosis and two constant torques at the hip for propulsion. We varied Ankle Foot
      Orthosis stiffness while keeping speed and step length constant. FINDINGS: We
      found an optimal stiffness, at which the energy delivered at the hip joint was
      minimal. Energy cost decreased with increasing energy storage in the ankle foot
      orthosis, but the most efficient gait did not occur with maximal energy storage.
      With maximum storage, push-off occurred too late to reduce the impact of the
      contralateral leg with the floor. Maximum return prior to foot strike was also
      suboptimal, as push-off occurred too early and its effects were subsequently
      counteracted by gravity. The optimal Ankle Foot Orthosis stiffness resulted in
      significant push-off timed just prior to foot strike and led to greater ankle
      plantar-flexion velocity just before contralateral foot strike. INTERPRETATION:
      Our results suggest that patient energy cost might be reduced by the proper
      choice of Ankle Foot Orthosis stiffness.

PMID- 21723013
TI  - Field controlled experiments of mercury accumulation in crops from air and soil.
AB  - Field open top chambers (OTCs) and soil mercury (Hg) enriched experiments were
      employed to study the influence of Hg concentrations in air and soil on the Hg
      accumulation in the organs of maize (Zea mays L.) and wheat (Triticum aestivum
      L.). Results showed that Hg concentrations in foliages were correlated
      significantly (p < 0.05) with air Hg concentrations but insignificantly
      correlated with soil Hg concentrations, indicating that Hg in crop foliages was
      mainly from air. Hg concentrations in roots were generally correlated with soil
      Hg concentrations (p < 0.05) but insignificantly correlated with air Hg
      concentrations, indicating that Hg in crop roots was mainly from soil. No
      significant correlations were found between Hg concentrations in stems and those
      in air and soil. However, Hg concentrations in upper stems were usually higher
      than those in bottom stems, implying air Hg might have stronger influence than
      soil Hg on stem Hg accumulation.

PMID- 21723014
TI  - Impacts of atmospheric pollution on the plant communities of British acid
      grasslands.
AB  - Air pollutants are recognised as important agents of ecosystem change but few
      studies consider the effects of multiple pollutants and their interactions. Here
      we use ordination, constrained cluster analysis and indicator value analyses to
      identify potential environmental controls on species composition, ecological
      groupings and indicator species in a gradient study of UK acid grasslands. The
      community composition of these grasslands is related to climate, grazing, ozone
      exposure and nitrogen deposition, with evidence for an interaction between the
      ecological impacts of base cation and nitrogen deposition. Ozone is a key agent
      in species compositional change but is not associated with a reduction in species
      richness or diversity indices, showing the subtly different drivers on these two
      aspects of ecosystem degradation. Our results demonstrate the effects of multiple
      interacting pollutants, which may collectively have a greater impact than any
      individual agent.

PMID- 21723015
TI  - Bisphosphonate-related osteonecrosis of jaws in 3 osteoporotic patients with
      history of oral bisphosphonate use treated with single yearly zoledronic acid
      infusion.

PMID- 21723016
TI  - Simple method for securing a decompression tube for odontogenic cysts and tumors:
      a technical note.

PMID- 21723017
TI  - Maxillary functional reconstruction using a reverse facial artery-submental
      artery mandibular osteomuscular flap with dental implants.
AB  - PURPOSE: This clinical study assessed the reverse facial artery-submental artery
      mandibular osteomuscular flap with titanium dental implants for the functional
      reconstruction of maxillary defects. PATIENTS AND METHODS: Class 2a defects in 5
      patients were repaired with a reverse facial artery-submental artery mandibular
      osteomuscular flap with titanium dental implants (n = 21). All patients received
      a fixed partial denture after a 3- to 6-month healing period. RESULTS: All
      lesions were widely excised in an area extending to the maxilla. Of the implants,
      20 (95.2%) were loaded and 1 was lost before loading. Reconstruction with a fixed
      partial denture was successful in all patients. The patients were followed up for
      12 to 20 months (mean, 15.8 months), and no recurrence was observed. CONCLUSION:
      The reverse facial artery-submental artery mandibular osteomuscular flap with
      titanium dental implants is safe, quick, and simple to elevate and is reliable
      for the functional reconstruction of maxillary defects.

PMID- 21723018
TI  - Double-barrel fibula vascularized free flap with dental rehabilitation for
      mandibular reconstruction.
AB  - PURPOSE: The vascularized free fibula flap has become the most popular
      reconstruction method after mandibular resection because of adequate bone graft
      length and acceptance of dental implants. However, using 1 fibula bone may
      produce a height discrepancy between the native mandible and the grafted fibula
      that results in subsequent difficulty in wearing conventional dentures or
      osteointegrated implants. Several options can be used to resolve this problem
      such as delayed onlay bone graft, iliac bone reconstruction, fibula distraction,
      and double-barrel fibula flap graft. This article describes the reconstruction of
      segmental mandible defects with the double-barrel fibula flap and denture
      rehabilitation. MATERIALS AND METHODS: This procedure was used in 7 patients. A
      donor site fibula corresponding to at least twice the length of the mandibular
      defect was harvested. Double-barrel free fibula grafting was performed in 6
      patients for primary reconstruction and 1 patient for secondary reconstruction,
      including 3 cases of osteocutaneous flap with skin islands in the reconstruction
      of a composite defect from a malignant tumor. Prosthodontic treatment was
      completed in all 7 patients. Four patients received secondary implant-supported
      dental reconstruction, and 3 patients who received radiation (6,000 cGy) after
      graft surgery had conventional removable partial dentures. RESULTS: Microvascular
      fibula transfers were completely successful, and all skin paddles survived
      without necrosis. The original mandibular contour was maintained by a
      reconstruction plate; the reconstruction mandibular length was 6.5 to 10 cm, the
      reconstruction height of the double-barrel fibula was 3.0 to 3.8 cm, and all
      patients were satisfied with the postoperative facial esthetics and chewing
      function from the implant-supported denture and removable partial prostheses.
      CONCLUSIONS: Mandibular segmental defects can be esthetically and functionally
      reconstructed by a double-barrel vascularized fibula flap that not only matches
      the height of the native mandible but also allows osteointegrated dental
      implantation for dental rehabilitation.

PMID- 21723019
TI  - A head and neck lymph node classification using an anatomical grid system while
      maintaining clinical relevance.
AB  - PURPOSE: The current classification of head and neck lymph nodes lacks a
      standardized system that integrates basic anatomy and clinical relevance.
      Currently, anatomy texts, atlases, and journals used to educate future health
      care professionals use a classification system that differs from the commonly
      used clinical nomenclature. As a result, student trainees entering the
      professional world are confused by lymph node terminology. The purpose of this
      study was to suggest a lymph node classification system that accurately reflected
      anatomy and clinical applications. MATERIALS AND METHODS: A literature search was
      conducted on anatomic and clinical texts, atlases, journals, and Web sites.
      RESULTS: Two recurring classification themes were found from anatomic texts and
      atlases: superficial and deep chains, and local anatomic structures. Since 1988
      the clinical specialties have used a Roman numeral "level" system. The
      differences between anatomic and clinical classification systems have led to
      academic frustration. After analysis, a functional classification system was
      developed that integrated anatomic and clinical terminology from the current
      classification systems. This suggested system revised the clinically accepted
      level system approved in 1988 and replaced the terminology with an anatomically
      derived naming system. CONCLUSION: This system satisfies the need for a
      classification that unifies anatomic and clinical applications.

PMID- 21723020
TI  - Temporomandibular joint replacement for ankylosis correction in Nager syndrome:
      case report and review of the literature.

PMID- 21723021
TI  - Chondroma (cartilaginous choristoma) of the tongue: report of a case.

PMID- 21723022
TI  - Labial salivary gland biopsy in the investigation of neonatal hemochromatosis.

PMID- 21723023
TI  - Changes in disc position, disc length, and condylar height in the
      temporomandibular joint with anterior disc displacement: a longitudinal
      retrospective magnetic resonance imaging study.
AB  - PURPOSE: To quantitatively assess the changes in disc position relative to the
      condyle, disc length, and condylar height, with magnetic resonance imaging in
      patients with anterior disc displacement of the temporomandibular joint who had
      received no treatment, to provide useful information regarding treatment
      planning. PATIENTS AND METHODS: The study included 83 joints in 62 patients. The
      joints were assessed quantitatively for the disc position relative to the
      condyle, disc length, and condylar height on magnetic resonance imaging scans of
      the temporomandibular joint at initial and follow-up visits. Student t tests were
      used to assess the statistical significance of the changes. RESULTS: The mean age
      at first visit was 30.4 years. The mean follow-up interval was 10.9 months.
      Thirty-nine joints were shown to have disc displacement with reduction at the
      initial visit. Of these joints, 27 changed to having disc displacement without
      reduction after follow-up. The mean disc position relative to the condyle changed
      from 5.28 to 6.73 mm, whereas the mean disc length changed from 8.31 to 6.91 mm
      and the mean condylar height from 5.21 to 4.65 mm. Differences were all
      statistically significant. CONCLUSIONS: The disc would likely become more
      anteriorly displaced and shortened and the condylar height would decrease during
      its natural course. However, further stratified studies with longer follow-up are
      necessary.

PMID- 21723024
TI  - Cognitive impairment and whole brain diffusion in patients with neuromyelitis
      optica after acute relapse.
AB  - The objective of this study investigated cognitive impairments and their
      correlations with fractional anisotropy (FA) and mean diffusivity (MD) in
      patients with neuromyelitis optica (NMO) without visible lesions on conventional
      brain MRI during acute relapse. Twenty one patients with NMO and 21 normal
      control subjects received several cognitive tests to assess cognitive function.
      Head diffusion tensor imaging (DTI) of all patients with NMO were collected with
      a 3-T MR system. Correlations of cognitive test scores and whole brain FA and MD
      were examined by voxel-based analysis. Region-of-interest analysis was applied to
      the significantly correlated regions which the most frequently appeared. We found
      that NMO patients without visible brain lesions had significantly impaired
      learning and memory, decreased information processing speed, and damaged
      attention compared with normal control subjects. These impaired cognitive domains
      were significantly correlated with FA and MD in local regions of corpus callosum,
      anterior cingulate and medial frontal cortex. In corpus callosum of NMO patients,
      mean FA was significantly lower and mean MD higher than normal control subjects.
      Our findings suggest that cognitive impairments in learning and memory,
      information processing speed and attention occur in NMO patients without visible
      brain lesions during acute relapse. The impairments in immediate and short-term
      memory in NMO patients may be due to information encoding deficits in the process
      of information acquisition. The corpus callosum of such patients may have local
      microscopic damages that play a role in cognitive impairments during acute
      relapse.

PMID- 21723025
TI  - Are ultrafine particles a risk factor for cardiovascular diseases?

PMID- 21723026
TI  - Blood pressure control in hypertensive women aged 65 years or older in a primary
      care setting. MERICAP study.
AB  - INTRODUCTION AND OBJECTIVES: The available information regarding blood pressure
      control in women is scarce. This study was aimed at assessing blood pressure
      control and predictors of a lack of blood pressure control in the primary care
      setting in a large sample of hypertensive women. METHODS: Women aged 65 years or
      older with an established diagnosis of hypertension (>= 6 months of evolution)
      were included in a cross-sectional, multicenter study. Blood pressure readings
      were taken following the current guidelines, and the value for each visit was the
      average of two separate measurements. Adequate blood pressure control was defined
      as < 140/90 mm Hg (< 130/80 mm Hg for diabetics). RESULTS: A total of 4274
      hypertensive women (mean age: 73.6 years [6.1 years]) were included in the study;
      blood pressure was controlled in 29.8% (95% confidence interval: 28.4%-31.1%) of
      the study population. Combined therapy was administered in 67.6% of patients
      (46.3% with 2 drugs and 21.7% with 3 or more drugs). The most common organ damage
      was left ventricular hypertrophy (33.8%) and the most common associated condition
      was heart failure (19%). Poor blood pressure control was more frequent in
      patients with more cardiovascular risk factors, organ damage, and associated
      clinical conditions (P<.01). A more recent hypertension diagnosis, LDL
      cholesterol > 115 mg/dl, monotherapy, obesity, and hemoglobin A(1c) >= 7% were
      associated with a lack of blood pressure control (P < .0001). CONCLUSIONS: Only 3
      in 10 hypertensive women aged >= 65 years monitored daily in the primary care
      setting achieved their blood pressure goals. A recent diagnosis of hypertension
      was the main predictor of poor blood pressure control.

PMID- 21723027
TI  - Out-of-hospital cardiac arrest: early in-hospital hypotension versus out-of
      hospital factors in predicting in-hospital mortality among those surviving to
      hospital admission.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of in
      hospital hypotension in patients surviving to admission after resuscitation from
      out-of-hospital cardiac arrest and compare it to that of traditional Utstein
      factors in predicting in-hospital mortality. METHODS: Single-center retrospective
      cohort of adult patients surviving to hospital admission after resuscitation from
      out-of-hospital sudden death between January 1, 2006 and October 31, 2009. Study
      variables included Utstein template data: age, sex, initial rhythm, witnessed or
      nonwitnessed arrest, presence or absence of bystander CPR, location of arrest,
      response time (time of 9-1-1 dispatch to first vehicle arrival), and hypotension
      (systolic pressure<90 or mean arterial pressure<60) within 24h of ROSC.
      Univariate comparisons of categorical variables were performed and the Wilcoxon
      rank-sum test was used to compare continuous variables. Multivariable logistic
      regression was then performed after inclusion of Utstein variables. RESULTS: 73
      patients met the inclusion criteria, and in-hospital mortality occurred in 54
      (74%). On univariate analysis, in-hospital hypotension (OR=3.5, 95%CI 1.1-10.0,
      p=0.02), pre-hospital rhythm other than VF/VT (OR 4.3, 95%CI 1.4-13.3, p=0.008),
      and an unwitnessed arrest (OR=6.9, 95%CI 0.8-56.5, p=0.04), were significant
      predictors of in-hospital mortality. On multivariable analysis, in-hospital
      hypotension (OR=9.8, 95%CI 1.5, 63.0, p=0.02), pre-hospital rhythm other than
      VT/VF (OR=8.5, 95%CI 1.3-58.8, p=0.03), and lack of bystander CPR (OR=13.2, 95%CI
      1.6-111, p=0.02) remained statistically significant predictors of in-hospital
      mortality. CONCLUSIONS: In-hospital hypotension was predictive of mortality, as
      was a pre-hospital nonshockable rhythm and lack of bystander CPR. In contrast,
      traditional pre-hospital risk factors: age, gender, public location of arrest,
      response time, and witnessed arrest, were not predictive.

PMID- 21723028
TI  - Training to deeper compression depth reduces shallow compressions after six
      months in a manikin model.
AB  - INTRODUCTION: Studies show that students, trained to perform compressions between
      40 and 50mm deep, often do not achieve sufficient depth at retention testing. We
      hypothesized that training to achieve depths >50mm would decrease the proportion
      of students with depth <40mm after 6 months, compared to students trained to a
      depth interval of 40-50mm. METHODS: A basic life support (BLS) self-learning
      station was attended by 190 third year medicine students. They were first offered
      the possibility to refresh their skills, following the instructions of a 15min
      abbreviated Mini AnneTM video (Laerdal, Norway) using a full size torso and a
      face shield. This was followed by further training using Resusci Anne Skills
      StationTM software (Laerdal, Norway). Voice feedback was provided according to
      randomisation to a standard group (SG) 40-50mm and a deeper group (DG) >50mm.
      Quality of compressions was tested after 6 months. RESULTS: The SG and DG groups
      consisted of 90 (67% female) and 100 (58% female) participants respectively. At
      the end of training, all students reached the target depth without overlap
      between groups. After 6 months, the proportion of students achieving a depth
      <40mm was 26/89 (29%) in the SG vs. 12/89 (14%) in the DG (P=0.01). The
      proportion of students with a depth >50mm was 5/89 (6%) for the SG and 44/89
      (49%) in the DG (P<0.001). CONCLUSIONS: The educational strategy to train
      students to a deeper depth, reduced shallow compressions 6 months after training.

PMID- 21723029
TI  - Influence of age on heart rate variability during therapeutic hypothermia in a
      rat model.
AB  - OBJECTIVES: To evaluate the effect of age on heart rate variability (HRV) in a
      rat model of therapeutic hypothermia. METHODS: Thirty-six male Sprague-Dawley
      rats (18 were 2 months old and 18 were 18 months old) were randomized into one of
      three groups: normothermia (37 degrees C), mild hypothermia (34 degrees C), and
      moderate hypothermia (31 degrees C). An electrocardiogram (ECG) was recorded at
      baseline and continuously for 1h once the target core body temperature was
      reached. Various heart rate variability measurements were calculated. RESULTS:
      Significant effects of age were observed in respect to the ratio of standard
      deviation of all normal to normal R-R [NN] intervals (SDNN)/standard deviation of
      the differences between adjacent NN intervals (SD of delta NN) (P=0.037), low
      frequency (LF) power, normalized units (nu, %) (P<0.001), and the ratio of LF and
      high frequency (HF) (P<0.001). Significant effects of temperature were found in
      LF power and a significant body-temperature interaction was found in HF power. HF
      power was significantly lower in the young rats at mild and moderate hypothermic
      conditions. For the LF/HF, the ratio was significantly lower in the young animals
      compared to the older animals at normal body temperatures and during mild
      hypothermia. LF/HF increased significantly at both 34 degrees C and 31 degrees C
      in the young rats compared to the young rats at 37 degrees C. In contrast, LF/HF
      was significantly lower in the older group of rats at 34 degrees C and 31 degrees
      C compared to the older group of rats maintained under normothermic conditions.
      CONCLUSIONS: This study noted that autonomic regulation determined via HRV,
      primarily the ratio of LF to HF, was different between different age groups.
      Additional studies on this topic are needed to achieve a more detailed
      understanding of therapeutic hypothermia.

PMID- 21723030
TI  - Vaginal cuff dehiscence after hysterectomy: a multicenter retrospective study.
AB  - OBJECTIVE: This study estimates the incidence of vaginal cuff dehiscence
      resulting from different approaches to hysterectomy. STUDY DESIGN: This
      multicentric study was carried out retrospectively. We retrospectively analyzed
      8635 patients; 37% underwent abdominal hysterectomy, 31.2% vaginal hysterectomy,
      and 31.8% laparoscopic hysterectomy. All the hysterectomies were considered,
      vaginal evisceration was registered and analyzed for time of onset, trigger
      event, presenting symptoms, details of prolapsed organs and type of repair
      surgery. Continuous variables were compared using the one-way analysis of
      variance between groups as all data followed a Gaussian distribution, as
      confirmed by the Kolmogorov-Smirnov test. Differences among subgroups were
      assessed using the Tukey-Kramer multiple comparisons test. Categorical variables
      were compared with two tailed Chi-square tests with Yates correction or Fisher's
      exact test, as appropriate. Pearson's linear correlation was used to verify
      linear relationships between the dehiscence interval and patient's age at
      surgery. RESULTS: Thirty-four patients (0.39%) experienced vaginal evisceration.
      The laparoscopic route was associated with a significantly higher incidence of
      dehiscence (p<0.05). No differences were found between the 6027 patients (69.8%)
      who had closure of the vaginal cuff and the 2608 (30.2%) who had an unclosed cuff
      closure technique. CONCLUSION: Vaginal evisceration after hysterectomy is a rare
      gynecological surgical complication. Sexual intercourse before the complete
      healing of the vaginal cuff is the main trigger event in young patients, while
      evisceration presents as a spontaneous event in elderly patients. Surgical repair
      can be performed either vaginally or laparoscopically with similar outcomes.

PMID- 21723031
TI  - Muscle specific differences in the regulation of myogenic differentiation in
      chickens genetically selected for divergent growth rates.
AB  - With the human population predicted to reach 9 billion by 2050, increasing food
      supplies while maintaining adequate standards of animal welfare has become a
      global priority. In the poultry industry, broilers are genetically selected for
      greater pectoral but not leg muscularity yield leading to leg disorders and
      thereby welfare issues. It is known that the pectoralis major of broilers
      contains more muscle fibres of larger diameters than egg-layers but little is
      known about the leg gastrocnemius muscle cellular characteristics. As muscle
      fibre numbers are set by hatch, the molecular regulation of myogenesis was
      investigated in pectoral (selected) and gastrocnemius (unselected) muscles of
      chick embryos to help explain diverging post-hatch phenotypes. Results showed
      that broilers were more active from embryonic day (ED) 8 and heavier from ED12 to
      18 than layers. The pectoral muscle of broilers exhibited increased myoblast
      proliferation on ED15 (raised myonuclei, MyoD and PCNA) followed by increased
      differentiation from ED16 (raised myogenin, IGF-I) leading to increased muscle
      fibre hyperplasia and mass by ED18 compared to layers. In the gastrocnemius
      muscle of broilers, cell proliferation was also raised up to ED15 accompanied by
      increased PCNA, MyoD and IGF-I mRNAs. However, from ED16, myogenin and IGF-I
      mRNAs were similar to that of layers and PCNA was reduced leading to similar
      fibre area, nuclei numbers and muscle mass at ED18. We conclude that genetic
      selection for enhanced post-hatch pectoral muscle growth has altered the temporal
      expression of IGF-I and thereby myogenin transcription affecting cellular
      characteristics and mass by hatch in a muscle specific manner. These observations
      should help develop intervention strategies aimed at improving leg muscle
      strength and thereby animal welfare to meet growing consumer demand.

PMID- 21723033
TI  - Sludge valorization from wastewater treatment plant to its application on the
      ceramic industry.
AB  - The main aim of this study is to assess the effect of incorporating waste sludge
      on the properties and microstructure of clay used for bricks manufacturing.
      Wastewater treatment plants produce annually a great volume of sludge. Replacing
      clay in a ceramic body with different proportions of sludge can reduce the cost
      due to the utilization of waste and, at the same time, it can help to solve an
      environmental problem. Compositions were prepared with additions of 1%, 2.5%, 5%,
      7.5%, 10% and 15% wt% waste sludge in body clay. In order to determine the
      technological properties, such as bulk density, linear shrinkage, water suction,
      water absorption and compressive strength, press-moulded bodies were fired at 950
      degrees C for coherently bonding particles in order to enhance the strength and
      the other engineering properties of the compacted particles. Thermal heating
      destroys organic remainder and stabilizes inorganic materials and metals by
      incorporating oxides from the elemental constituent into a ceramic-like material.
      Results have shown that incorporating up to 5 wt% of sludge is beneficial for
      clay bricks. By contrast, the incorporation of sludge amounts over 5 wt% causes
      deterioration on the mechanical properties, therefore producing low-quality
      bricks.

PMID- 21723032
TI  - A historical perspective on the role of stroma in the pathogenesis of benign
      prostatic hyperplasia.
AB  - This review summarizes the concept that the neo-formation of ductal-acinar
      architecture in the pathogenesis of benign prostatic hyperplasia (BPH) is due to
      the reactivation of embryonic inductive activity by BPH stroma, an idea
      enunciated by John McNeal. The concept is the synthesis of McNeal's astute
      pathological inference based upon developmental biology and supported by the
      mesenchymal-epithelial interaction studies. In a broader context, McNeal's
      concept of framing epithelial pathogenesis in terms of developmental biological
      principals has been extended more recently into the field of carcinogenesis under
      the umbrella of tumor microenvironment.

PMID- 21723034
TI  - A population-based analysis of temporal perioperative complication rates after
      minimally invasive radical prostatectomy.
AB  - BACKGROUND: Existing population-based reports on complication rates after
      minimally invasive radical prostatectomy (MIRP) did not address temporal trends.
      OBJECTIVE: To examine contemporary temporal trends in perioperative MIRP
      outcomes. DESIGN, SETTING, AND PARTICIPANTS: Between 2001 and 2007, 4387 patients
      undergoing MIRP were identified using the Nationwide Inpatient Sample.
      MEASUREMENTS: To examine the rates and trends of intraoperative and postoperative
      complications, transfusion rates, length of stay in excess of the median, and in
      hospital mortality. We tested the effect of the late (2006-2007) versus the early
      (2001-2005) study period on all outcomes using multivariable logistic regression
      models controlled for clustering among hospitals. RESULTS AND LIMITATIONS:
      Intraoperative and postoperative complications decreased from 7.0% to 0.8% (p <
      0.001) and from 28.5% to 8.7% (p < 0.001), respectively. Transfusion rates
      decreased from 3.5% to 2.1% (p = 0.3). Hospital length of stay >2 d decreased
      from 56% to 15% (p < 0.001). In multivariable analyses, intraoperative (odds
      ratio [OR]: 0.41; p = 0.002) and postoperative (OR: 0.65; p = 0.007)
      complications were less frequent in the late versus the early study period. Late
      study period patients were less likely to stay >2 d than early study period
      patients (OR: 0.34; p > 0.001). Limitations of these findings include the lack of
      adjustment for several patient variables including disease characteristics,
      surgeon variables including surgeon caseload, and the restriction to in-hospital
      events. CONCLUSIONS: Our analyses demonstrate that in-hospital complication rates
      and length of stay after MIRP decreased over time. This implies that temporal
      differences specific to complication rates after MIRP must be considered when
      comparisons are made with other radical prostatectomy techniques.

PMID- 21723035
TI  - TMEM14A inhibits N-(4-hydroxyphenyl)retinamide-induced apoptosis through the
      stabilization of mitochondrial membrane potential.
AB  - Apoptosis is a highly conserved genetic process leading to death in mammalian
      cells. A critical step in apoptosis is mitochondrial membrane permeabilization,
      which results in the release of proteins critical to downstream events.
      Transmembrane protein 14A (TMEM14A) was identified as a novel suppressor of Bax
      using yeast-based functional screening. TMEM14A is a novel mitochondria
      associated membrane protein containing a putative transmembrane domain. Over
      expression of TMEM14A in U87MG cells inhibited N-(4-hydroxyphenyl)retinamide (4
      HPR)-induced apoptosis. TMEM14A prevented 4-HPR-induced loss of mitochondrial
      membrane potential (MMP), the release of cytochrome c, and the activation of
      caspase-3, but not the generation of reactive oxygen species, suggesting that
      TMEM14A regulates mitochondrial membrane potential in a ROS-independent manner.
      As expected, cyclosporin A, an inhibitor of membrane potential transition,
      inhibited 4-HPR-induced loss of MMP and apoptosis in U87MG cells, indicating that
      loss of MMP plays a pivotal role in 4-HPR-induced apoptosis. Suppression of
      TMEM14A expression using shRNA significantly increased apoptosis and MMP loss in
      untreated and 4-HPR-treated cells. These findings show for the first time that
      TMEM14A inhibits apoptosis by blocking the mitochondrial permeability transition
      and stabilizing mitochondrial membrane potential.

PMID- 21723036
TI  - Application of dolochar in the removal of cadmium and hexavalent chromium ions
      from aqueous solutions.
AB  - Dolochar, a waste material generated in sponge iron industry, is processed and
      put to test as an adsorbent for removal of Cd(II) and Cr(VI) ions from aqueous
      solutions. The dolochar samples were characterised to determine the different
      phases and their distribution by reflection microscopy. The analysis indicated
      that the sample consists of metallic iron, fused carbon, and Ca-Mg bearing phases
      (Ca-Mg-silicate-oxide) along with lots of voids and pores. The fixed carbon (FC)
      content of the material is 13.8% with a Langmuir surface area of 81.6m(2)/g and
      micropore area of 34.1m(2)/g. Batch adsorption experiments have been conducted to
      study the sorption behaviour of Cd(II) and Cr(VI) ions on dolochar as a function
      of particle size, contact time, adsorbent dosages, pH and temperature. It is
      observed that higher pH and temperature enhances sorption of Cd(II) ions. In
      contrast, the adsorption for Cr(VI) is found to be better in acidic pH in
      comparison to alkaline media. The equilibrium adsorption isotherm data are tested
      by applying both Langmuir and Freundlich isotherm models. It is observed that
      Langmuir isotherm model fitted better compared to the Freundlich model indicating
      monolayer adsorption. The thermodynamic parameters such as DeltaG degrees ,
      DeltaH degrees  and DeltaS degrees  indicate the effectiveness of dolochar to
      remove Cd(II) and Cr(VI) ions from aqueous solution. The kinetics of adsorption
      is found to better fit to pseudo second order reaction.

PMID- 21723037
TI  - Nontricyclic antidepressant analgesics and pain: are serotonin norepinephrine
      reuptake inhibitors (SNRIs) any better?

PMID- 21723038
TI  - Response to the article of Ernst et al. Acupuncture: does it alleviate pain and
      are there serious risks? A review of reviews. [Pain 2011;152:755-64].

PMID- 21723039
TI  - Effects of self-discrepancies on activity-related behaviour: explaining
      disability and quality of life in patients with chronic low back pain.
AB  - In chronic low back pain (CLBP) research, the self-discrepancy model has been
      applied to explain dysfunctional avoidance and persistence behaviour. The main
      aim of this study was to evaluate whether specific self-discrepancies in patients
      with CLBP are associated with the abovementioned types of activity-related
      behaviour and whether changes in self-discrepancies over time are associated with
      changes in activity-related behaviour. Furthermore, the aim was to evaluate
      whether avoidance and persistence behaviour are associated with a higher level of
      disability and a diminished quality of life and whether changes over time in
      avoidance and persistence behaviour result in changes in disability and quality
      of life. A longitudinal cohort study in a sample of patients with CLBP (N=116),
      in which self-discrepancies, disability, quality of life, and objectively
      registered characteristics of activity-related behaviour were measured, was
      performed to evaluate the pathways in the aforementioned self-discrepancy model.
      Results indicate that patients with CLBP who feel closer to their ideal-other
      show more characteristics of persistence behaviour. Patients who move further
      away from their ideal-own also show more characteristics of persistence
      behaviour. Furthermore, in patients characterized as avoider, a decrease in a
      patient's daily uptime was associated with a decrease of mental health-related
      quality of life.

PMID- 21723040
TI  - Towards sustainable parasite control practices in livestock production with
      emphasis in Latin America.
AB  - Endo and ectoparasites of domestic ruminants directly or indirectly contribute to
      reduce sustainability affecting food security in subsistence or small scale
      farming systems, food safety (food borne diseases and pesticide residues),
      environment (pesticides, pollution and ecotoxicity) and farmer's equity (limited
      or uneven access to relevant technical information/training). This is especially
      true for some regions of Latin America where there still are huge areas of
      natural grazing land for cattle, sheep and goats. Sustainable parasite control is
      not an absolute concept given the different regions and productive systems of the
      world and therefore, could have different levels of adoption and impact on
      farmers. This article develops a conceptual framework to better understand where
      each region or country is situated in terms of attaining a reasonable increase in
      animal production while preserving sustainability. Within this context the
      capacity to prioritize the target parasite species for control according to local
      epidemiology and production systems, the early diagnosis and monitoring of
      parasite resistance as well as the availability of well trained field
      professionals acquire a major role, creating an enabling environment for present
      and future decision support system approaches. Until new and different means of
      controlling parasites become available; the challenge is to utilize Good Animal
      Husbandry Practices and Integrated Parasite Management (IPM) principles in a
      pragmatic way allowing the rational use of pesticides.

PMID- 21723041
TI  - Detection of Trichinella murrelli in coyotes (Canis latrans) from Oklahoma and
      North Texas.
AB  - We determined the prevalence and mean intensity of Trichinella sp. infection in
      coyotes from six counties in Oklahoma and one in northern Texas. Tongues from 77
      coyotes were examined using histology and artificial tissue digestion.
      Histological examination showed a prevalence of 3.9% (3 of 77) whereas the
      prevalence was 6.5% (5 of 77) based on artificial digestion of 5.0 g of muscle
      from coyote tongues. One sample was positive for Trichinella sp. on histology but
      negative by artificial digestion. Combining data from both diagnostic techniques
      showed that six of 77 (7.8%) coyotes were infected with Trichinella spp. The mean
      intensity of Trichinella sp. larvae ranged from 0.2 to 66.2 with an average of
      16.0 larvae per gram (LPG) of tongue. Genotyping results demonstrated that the
      coyotes were infected with Trichinella murrelli. This is the first report of T.
      murrelli infection in coyotes in Oklahoma. T. murrelli had previously been
      isolated from coyotes in Texas.

PMID- 21723043
TI  - Revolving-door flap: an alternative for the coverage of acute burn defects of the
      auricle.

PMID- 21723044
TI  - A prospective randomized controlled trial comparing negative pressure dressing
      and conventional dressing methods on split-thickness skin grafts in burned
      patients.
AB  - INTRODUCTION: Split-thickness skin grafting (SSG) is a technique used extensively
      in the care of burn patients and is fraught with suboptimal graft take when there
      is a less-than-ideal graft bed and/or grafting conditions. The technique of
      Negative Pressure Dressing (NPD), initially used for better wound healing has
      been tried on skin-grafts and has shown to increase the graft take rates.
      However, comparative studies between the conventional dressing and vacuum
      assisted closure on skin grafts in burn patients are unavailable. The present
      study was undertaken to find out if NPD improves graft take as compared to
      conventional dressing in burns patients. MATERIALS AND METHODS: Consecutive burn
      patients undergoing split-skin grafting were randomized to receive either a
      conventional dressing consisting of Vaseline gauze and cotton pads or to have a
      NPD of 80 mm Hg for four days over the freshly laid SSG. The results in terms of
      amount of graft take, duration of dressings for the grafted area and the cost of
      treatment of wound were compared between the two groups. RESULTS: A total of 40
      split-skin grafts were put on 30 patients. The grafted wounds included acute and
      chronic burns wounds and surgically created raw areas during burn reconstruction.
      Twenty-one of them received NPD and 19 served as controls. Patient profiles and
      average size of the grafts were comparable between the two groups. The vacuum
      closure assembly was well tolerated by all patients. Final graft take at nine
      days in the study group ranged from 90 to 100 per cent with an average of 96.7
      per cent (SD: 3.55). The control group showed a graft take ranging between 70 and
      100 percent with an average graft take of 87.5 percent (SD: 8.73). Mean duration
      of continued dressings on the grafted area was 8 days in cases (SD: 1.48) and 11
      days in controls (SD: 2.2) after surgery. Each of these differences was found to
      be statistically significant (p<0.001). CONCLUSION: Negative pressure dressing
      improves graft take in burns patients and can particularly be considered when
      wound bed and grafting conditions seem less-than-ideal. The negative pressure can
      also be effectively assembled using locally available materials thus
      significantly reducing the cost of treatment.

PMID- 21723045
TI  - Gradual cessation of proton pump inhibitor (PPI) treatment may prevent rebound
      acid secretion, measured by the alkaline tide method, in dyspepsia and reflux
      patients.
AB  - Gastro esophageal reflux disease and ulcer related or non-ulcer dyspepsia,
      attacks 20% of the Western population. These millions of patients are treated
      continuously with PPI for different periods, many for many years. Recently,
      rebound acid hypersecretion was recognized as a major clinical event after
      cessation of PPI therapy. Sustained hypergastrinemia due to daily PPI therapy
      causes increased acid-secretory capacity that appears when the drug is stopped.
      The transient increase in blood and urinary pH following gastric secretion has
      been termed the alkaline tide phenomenon. Carbonic acid, formed in the presence
      of the enzyme carbonic anhydrase, neutralizes intracellular hydroxyl ions
      produced as a result of luminal acid secretion. The bicarbonate generated is
      removed from the cell via the baso-lateral chloride bicarbonate exchanger. We
      have shown in several studies that this phenomenon parallels acid secretion.
      Thus, stimulation of acid secretion with test meal increased base excess
      maximally after 45 min and these changes parallel peak acid output measured in
      gastric aspirate. We hypothesize that gradual step down cessation of PPI will
      prevent this clinical relevant event. By measuring alkaline tide after PPI
      cessation we may prove this hypothesis.

PMID- 21723046
TI  - A deleterious BRCA1 mutation in a young Pakistani woman with metaplastic breast
      carcinoma.
AB  - Metaplastic breast carcinoma (MBC) is a relatively rare subtype of breast cancer
      that encompasses a pathologically heterogeneous group of tumors. Pathogenic germ
      line mutations in the major breast cancer susceptibility genes BRCA1 and BRCA2
      genes have been rarely found or described in MBC. We report the identification of
      the BRCA1 185delAG mutation in a 22-year-old Pakistani woman with triple-negative
      MBC that showed biphasic morphological features, including sarcomatous and
      malignant epithelial components. A comprehensive description of the clinical,
      histopathological, morphological, and immunohistochemical features of the tumor
      and the patient's treatment course is presented.

PMID- 21723047
TI  - Tyrosine kinase receptor RON and its ligand MSP in Merkel cell carcinoma.
AB  - The RON gene, encoding the tyrosine-kinase receptor for macrophage-stimulating
      protein (MSP), is involved in a range of neoplastic processes. However, no
      aberration in RON or MSP has been identified in Merkel cell carcinoma (MCC). We
      investigated the RON signaling pathway in MCC. Fourteen cases of MCC were tested
      for the expression of RON and its ligand, MSP, using reverse transcription PCR
      (RT-PCR) and immunohistochemistry. The mutation of RON was also examined. RT-PCR
      identified transcription of both RON and MSP in all nine cases that were
      available for the examination. Immunohistochemistry showed the expression of RON
      (9/14 cases) and MSP (9/14 cases). Six cases out of 14 were positive for both RON
      and MSP. Normal Merkel cells were negative for RON and MSP expression. Missense
      mutation in the tyrosine kinase region of RON was detected in one of the 14
      cases, and the case showed expression of RON. Transcription of RON and MSP was
      observed in MCC, and a considerable number of MCC cases expressed both RON and
      MSP, while Merkel cells do not express these molecules. The results suggest that
      RON signaling seems to play at least some role in the pathogenesis of MCC.

PMID- 21723048
TI  - [M. bovis and M. caprae infections in Aquitaine: A clinico-epidemiologic study of
      15 patients].
AB  - The agent of bovine tuberculosis, Mycobacterium bovis, is a zoonosis which can be
      transmitted to human beings. In France, the prevalence of tuberculosis due to M.
      bovis has drastically decreased, both for animals and humans, since public health
      measures were introduced to prevent its transmission. However, a new outbreak of
      the disease is noted among cattle in several French areas and more particularly
      in Aquitaine. In 2008, 40% of bovine tuberculosis French cases provided from
      Aquitaine. From November 2004 to October 2008, 15 cases were registered at
      Bordeaux's academic hospital (CHU). Thirteen of them were due to M. bovis and two
      to Mycobacterium caprae. It represents 2.9% of tuberculosis due to tuberculosis
      complex. An analysis of the 15 patients' medical files showed that it occurred
      either to old people who reactivated a former infection, or to younger ones who
      were born in countries with a strong M. bovis endemic disease. Extrapulmonary
      forms and especially ganglionics ones are the most frequent. M. caprae seems to
      be an emergent species among animal mycobacteries transmissible to human being.
      An epidemiological monitoring seems to be necessary to establish a relation
      between the regional outbreak of bovine tuberculosis and human tuberculosis.

PMID- 21723049
TI  - Mindfulness training for smoking cessation: results from a randomized controlled
      trial.
AB  - BACKGROUND: Cigarette smoking is the leading cause of preventable death in the
      world, and long-term abstinence rates remain modest. Mindfulness training (MT)
      has begun to show benefits in a number of psychiatric disorders, including
      depression, anxiety and more recently, in addictions. However, MT has not been
      evaluated for smoking cessation through randomized clinical trials. METHODS: 88
      treatment-seeking, nicotine-dependent adults who were smoking an average of
      20cigarettes/day were randomly assigned to receive MT or the American Lung
      Association's freedom from smoking (FFS) treatment. Both treatments were
      delivered twice weekly over 4 weeks (eight sessions total) in a group format. The
      primary outcomes were expired-air carbon monoxide-confirmed 7-day point
      prevalence abstinence and number of cigarettes/day at the end of the 4-week
      treatment and at a follow-up interview at week 17. RESULTS: 88% of individuals
      received MT and 84% of individuals received FFS completed treatment. Compared to
      those randomized to the FFS intervention, individuals who received MT showed a
      greater rate of reduction in cigarette use during treatment and maintained these
      gains during follow-up (F=11.11, p=.001). They also exhibited a trend toward
      greater point prevalence abstinence rate at the end of treatment (36% vs. 15%,
      p=.063), which was significant at the 17-week follow-up (31% vs. 6%, p=.012).
      CONCLUSIONS: This initial trial of mindfulness training may confer benefits
      greater than those associated with current standard treatments for smoking
      cessation.

PMID- 21723050
TI  - Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth
      weight.
AB  - BACKGROUND: Early iron supplementation in women with sufficient reserves could
      provoke iron excess resulting in haemoconcentration and low infant birth weight
      (IBW). AIM: To clarify the influence of early iron supplementation on maternal
      iron status and the IBW, taking into account pre-pregnancy iron deposits. STUDY
      DESIGN: Longitudinal, prospective study. SUBJECTS: Healthy women volunteers
      (n=82) intending to become pregnant. OUTCOME MEASURES: Women were grouped as a
      function of their pre-pregnancy (low or present) iron stores (serum ferritin
      (SF)<or>=20MUg/L) and time of commencement of iron supplementation during
      pregnancy; "early" (<20weeks) or "late" (>=20weeks). Obstetric and clinical
      history, smoking habit, dietary intake and iron biochemical parameters were
      obtained at pre-pregnancy as well as at 1st, 2nd and 3rd trimesters. Haemoglobin,
      MCV, SF and transferrin saturation (TS) were measured. RESULTS: Overall, 36% of
      the women had low iron stores at pre-pregnancy. The mean early supplementation
      with iron was 140.7mg/d and the mean of late supplementation was 99.01mg/d. Early
      supplementation improves the biochemical status of the mother and does not
      provoke a significant increase in haemoconcentration relative to late
      supplementation independently of the pre-pregnancy iron levels. Supplemental iron
      had a positive effect on birth weight among women with pre-pregnancy low iron
      stores (beta=4.37; SE=1.8; p=0.038) and did not affect birth weight among women
      with present iron stores (beta=-0.008; SE=3.03; p=0.998). CONCLUSION: Early iron
      supplementation with doses ~100mg/d improves the biochemical status of the mother
      independently of her pre-pregnancy iron status. Supplementation with iron
      improves newborn birth weight in those women who start pregnancy with iron
      deficiency, and makes no significant difference to those women who are not iron
      deficient.

PMID- 21723051
TI  - Prediction of developmental performance in preterm infants at two years of
      corrected age: contribution of the neurological assessment at term age.
AB  - BACKGROUND: The population of preterm infants is increasing and resources
      available for follow-up are limited. Early markers are needed to identify
      children who will show major as well as more subtle neurodevelopmental
      impairments. Such a challenge could be achieved with the Amiel-Tison Neurological
      Assessment at Term (ATNAT). AIMS: This study assesses the usefulness of the ATNAT
      in the prediction of developmental problems at two years of corrected age (CA) in
      infants born between 29 and 37 weeks of gestation. METHOD: Inclusion criteria
      were: gestational age between 29(0/7) and 36(6/7) weeks inclusively, birth weight
      below 2500g and minimal 24-hour stay in the Neonatal Intensive Care Unit of
      Sainte-Justine Hospital. A sample of 147 was prospectively recruited and assessed
      at two ages: at term with the ATNAT and at 24months CA with Bayley Scales of
      Infant Development-II. RESULTS: No major impairment such as cerebral palsy and no
      neurosensory impairment were observed. Developmental delay defined by an index<70
      on the mental or psychomotor scale was reported respectively in 6.2% and 5.4% of
      the cohort. Significant differences in mental, psychomotor and behavioral
      performances were found according to neurological status. Neurological status was
      the only variable to enter the predictive model for psychomotor and behavioral
      indexes. Gender and neurological status remained in the predictive model for
      mental performance. CONCLUSION: This study supports the inclusion of the ATNAT
      among the eligibility criteria for systematic neurodevelopmental surveillance as
      it allows early identification of infants at higher risk of low developmental
      performances at 24months CA.

PMID- 21723052
TI  - Nocturia in women.
AB  - Nocturia is a common problem in adults, which adversely affects quality of sleep
      and quality of life. This review summarizes the definition, epidemiology,
      clinical presentation, pathophysiology, diagnostic evaluation, and the
      therapeutic options with regard to a female population. Based on the degree of
      bother nocturia is classified as two or more episodes per night. It is most
      prevalent in older woman but also affects younger individuals. Voiding during
      nighttime leads to a disruption of sleep, affecting both sleep onset and
      maintenance. A clear understanding of its underlying pathophysiology, including
      diurnal polyuria, nocturnal polyuria, and bladder storage problems is necessary
      to address symptoms and co-morbid conditions. Diagnostic evaluation includes a
      detailed patient's history, physical examination, laboratory tests, and a voiding
      bladder diary. For treatment, tailored lifestyle and behavioural changes are able
      to decrease bother. In addition some patients profit from pharmacological therapy
      with antimuscarinic agents and analogue of arginine vasopressin, however this
      strategy is often restricted by side effects.

PMID- 21723053
TI  - Menopausal hormone therapy--benefits, adverse reactions, concerns and information
      sources in 2009.
AB  - OBJECTIVES: The aim of this study was to examine hormone therapy (HT) users'
      experiences, perceptions and information sources in 2009. STUDY DESIGN:
      Questionnaire survey was conducted in 2009 among women using HT. The
      questionnaire (n=500) was distributed from pharmacies across Finland. The
      response rate was 58% (n=281). MAIN OUTCOME MEASURES: The survey measured self
      reported benefits and adverse reactions, fears and information sources. RESULTS:
      The number of systemic HT users reporting fears was 50% (n=99). The most common
      fear was breast cancer (27%). Systemic HT users who had considered
      discontinuation of HT or had temporarily discontinued HT experienced fears more
      often than other respondents (p<0.001 and p=0.029). The most common source of
      information on the benefits of HT in both surveys was a physician (91%), whereas
      the most common source of information on adverse reactions was the media (54%).
      Vaginal HT users had experienced similar fears as users of systemic HT.
      CONCLUSIONS: Women using HT need more information about the risks of HT from
      their physician. This is especially important for women who are not able to
      manage the symptoms without HT, but have tried or considered discontinuation and
      for vaginal HT users.

PMID- 21723054
TI  - Factors related to menopausal symptom management decisions.
AB  - OBJECTIVE: To systematically review the literature regarding factors related to
      women's menopausal symptom management decision making. METHODS: The PubMed.gov
      online search engine was queried using pre-selected inclusion and exclusion
      criteria. Reference lists of articles were also reviewed to identify potentially
      missed articles. Full-text, English-language, peer-reviewed articles on factors
      related to menopausal symptom management decisions were reviewed. RESULTS: A
      total of 16 articles (15 data-based, 1 review of literature) from 6 different
      countries were reviewed. Most articles were related to decisions about one class
      of therapies and did not take into account all available therapeutic options. In
      the 15 data-based articles, diverse methods were used: qualitative (47%),
      quantitative (47%), and mixed (6%), with most being cross-sectional (93%). Very
      few of the data-based articles were based on a conceptual model (20%) and none
      used findings to derive an explanatory or predictive model. Most samples were not
      representative of special populations, such as women with breast cancer. Factors
      fell into four broad categories: (1) individual characteristics (demographics,
      menopause experience, symptomatology); (2) values, attitudes, beliefs, and
      preferences (attitudes and beliefs about menopause and treatments, preferred
      modalities, tolerance for risks/side effects); (3) facts and information about
      menopause and symptom management (amount, type, source, credibility,
      availability); and (4) health care context (health care provider communication,
      trust, availability/time, knowledge, relationship). CONCLUSIONS: Additional
      descriptive studies are needed understand women's menopausal symptom management
      decisions in the context of all available therapies so that a comprehensive model
      of menopausal symptom management decision making can be specified. Additional
      understanding is needed regarding decisions in special populations of menopausal
      women such as breast cancer survivors, a group for whom menopausal symptom
      management can be particularly complex.

PMID- 21723055
TI  - Age estimation using CT imaging of the third molar tooth, the medial clavicular
      epiphysis, and the spheno-occipital synchondrosis: a multifactorial approach.
AB  - A multi-factorial method for estimating age was devised based on the development
      of the 3rd molar tooth, the medial clavicular epiphysis, and the spheno-occipital
      synchondrosis, using multiple regression as the means to construct age estimation
      formulae and CT scanning as the imaging modality. The sample consisted of
      approximately 600 individuals from a contemporary Australian population, between
      the ages of 15 and 25 years, who were admitted to the Victorian Institute of
      Forensic Medicine, Melbourne, Australia, for the purposes of medico-legal death
      investigation. Results show that the spheno-occipital synchondrosis does not
      contribute to the age estimation model for this age cohort. The regression
      computation for the 3rd molar tooth and medial clavicle, when combined into a
      single multiple regression calculation, provides a robust model with tighter age
      ranges at the 95% confidence interval (CI) than when each age marker is used
      individually. This research provides a method to estimate age for unknown age
      Australian individuals in the problematic age group of 15-25 years with greater
      precision than previously possible.

PMID- 21723056
TI  - Survival of submerged blowfly species and their parasitoids: implications for
      postmortem submersion interval.
AB  - Pupal survival of three blowfly species, Chrysomya albiceps, Chrysomya
      megacephala, and Chrysomya putoria (Diptera: Calliphoridae) and the parasitoid
      species Nasonia vitripennis (Hymenoptera: Pteromalidae) was studied after the
      pupae were experimentally submerged in water. Non-parasitized pupae at different
      developmental stages, 0, 24, 48, and 72 h, and parasitized pupae after 3, 8, 10,
      and 12 days of development were submerged for 6, 24, 48, or 72 h. Control groups
      for each pupal developmental stage (parasitized or not), which were not
      submerged, were also observed in order to compare the adult emergence rates. The
      survival of white pupae (0 h/age) decreased with time of submergence for all
      three blowfly species, showing the lowest rates compared with other experimental
      pupa groups. For the three blowfly species, non-parasitized pupae at 24 and 48 h
      of age showed survival rates above 60%. However, for pupae at 72 h of age, the
      survival rates decreased with increased underwater time, with less than 30%
      survival after 72 h in C. putoria and C. albiceps. The survival of parasitoids
      inside blowfly pupae that were submerged during their larval stage (3 days/age)
      decreased with the increase of submergence time. After the parasitoids reached
      the pre-pupal life stage, the survival was higher for all underwater periods.
      These observations can be useful in investigations of the decomposition of
      partially submerged bodies, or in cases of pupae found adhering to decaying
      flesh, hair, or clothes of corpses that were submerged after the larvae had
      developed and pupated.

PMID- 21723057
TI  - Severity of vehicle bumper location in vehicle-to-pedestrian impact accidents.
AB  - Pedestrian protection is one of the key topics for safety measures in traffic
      accidents all over the world. To analyze the relation between the collision site
      of the vehicle bumper and the severity of the lower extremity injuries, we
      performed biomechanical experiments. We compared the applied external force and
      the risks of subsequent injuries between the impact of the center and side
      positions of the front bumper. These comparisons were performed by practical
      impact tests with eight typical different types of cars which were typical of the
      current vehicle fleets. The tests were made using the TRL legform impactor which
      was a mechanical substitute of a pedestrian lower extremity. The TRL impactor is
      used all over the world for assessing the safety of car bumpers. It was found
      that the risks of lower extremity injuries in the impacts at the side positions,
      in front of the vehicle's side member, were significantly higher than those at
      the center. In the tests, we found that foam materials around the rigid front
      cross member had a significant effect on reducing the lower extremity injury
      risks and especially tibia fracture risk against vehicle bumper center
      collisions, but had little effect at the sides of the bumper over the vehicle's
      side members where the foam was thinner. We also found that the front shape of
      the vehicle affected the risk of ligaments injuries. According to these results,
      the information of impact locations of cars in vehicle-to-pedestrian traffic
      accidents is valuable for clinicians to diagnose patients with lower extremity
      injuries in traffic accidents and for forensic pathologists to analyze the
      accident reconstruction. Furthermore, the results suggest that testing of the
      bumper area in front of the main longitudinal beams should be included in the car
      safety legislation to require pedestrian safety.

PMID- 21723058
TI  - Multiple cavitations in posterior reversible leukoencephalopathy syndrome
      associated with hemolytic-uremic syndrome.
AB  - We describe a 4-year-old boy with posterior reversible leukoencephalopathy
      syndrome associated with hemolytic-uremic syndrome. He exhibited bloody stool by
      Escherichia coli O157: H7 infection with acute renal failure. He subsequently
      presented high blood pressure, followed by visual disturbance and loss of
      consciousness. Brain MRI revealed bilateral occipital high intensities by T2
      weighted images and high value by apparent diffusion coefficient map, thus we
      made a diagnosis of posterior reversible leukoencephaly syndrome associated with
      hemolytic-uremic syndrome. In spite of immediate blood pressure control,
      occipital lesions developed day by day, resulting in multiple subcortical
      cavitations. Although posterior reversible leukoencephalopathy syndrome is
      originally characterized by reversible vasogenic edema, this case rarely resulted
      in irreversible changes with cystic formation. We concluded that precipitating
      factors, i.e., clotting abnormalities, Shiga toxin, vasospasms and endothelial
      dysfunction might have synergistically induced irreversible brain infarcts, and
      caused unusual cavitations.

PMID- 21723059
TI  - Acute encephalopathy with a lesion of the splenium of the corpus callosum--a
      report of two cases.
AB  - We report two cases of encephalopathy following a short febrile illness. Case one
      was a five year old child whose magnetic resonance imaging (MRI) of the brain
      showed a reversible discrete lesion in the splenium of the corpus callosum (SCC)
      and a ten year old boy who had extensive hyperintensity of the SCC. As these
      children have presented while there was an outbreak of influenza in our locality
      and since the second child tested positive for H1N1 antigen on PCR test, we feel
      that as previous authors have pointed out, these cases are cases of possible
      influenza encephalopathy. This awareness needs to be disseminated as this
      specific MRI finding should prompt one to test for H1N1 antigen and offer
      specific antiviral agent. Case one showed signs that support the existence of a
      splenial syndrome.

PMID- 21723060
TI  - Arcobacter ellisii sp. nov., isolated from mussels.
AB  - As part of a study carried out for detecting Arcobacter spp. in shellfish, three
      mussel isolates that were Gram-negative slightly curved rods, non-spore forming,
      showed a new 16S rDNA-RFLP pattern with a specific identification method for the
      species of this genus. Sequences of the 16S rRNA gene and those of the
      housekeeping genes rpoB, gyrB and hsp60 provided evidence that these mussel
      strains belonged to an unknown genetic lineage within the genus Arcobacter. The
      similarity between the 16S rRNA gene sequence of the representative strain (F79
      6(T)) and type strains of the other Arcobacter species ranged between 94.1% with
      A. halophilus and 99.1% with the recently proposed species A. defluvii (CECT
      7697(T)). DDH results between strain F79-6(T) and the type strain of the latter
      species were below 70% (53+/-3.0%). Phenotypic characteristics together with
      MALDITOF mass spectra differentiated the new mussel strains from all other
      Arcobacter species. All the results indicate that these strains represent a new
      species, for which the name Arcobacter ellisii sp. nov. with the type strain F79
      6(T) (=CECT 7837(T)=LMG 26155(T)) is proposed.

PMID- 21723061
TI  - Endogenous cardiac stem cell activation by insulin-like growth factor
      1/hepatocyte growth factor intracoronary injection fosters survival and
      regeneration of the infarcted pig heart.
AB  - OBJECTIVES: The purpose of this study was to test the ability of insulin-like
      growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident
      endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote
      myocardial repair through a clinically applicable intracoronary injection
      protocol in a pig model of myocardial infarction (MI) relevant to human disease.
      BACKGROUND: In rodents, cardiac stem/progenitor cell (CSC) transplantation as
      well as in situ activation through intramyocardial injection of specific growth
      factors has been shown to result in myocardial regeneration after acute
      myocardial infarction (AMI). METHODS: Acute MI was induced in pigs by a 60-min
      percutaneous transluminal coronary angiography left anterior descending artery
      occlusion. The IGF-1 and HGF were co-administered through the infarct-related
      artery in a single dose (ranging from 0.5 to 2 MUg HGF and 2 to 8 MUg IGF-1) 30
      min after coronary reperfusion. Pigs were sacrificed 21 days later for dose
      response relationship evaluation by immunohistopathology or 2 months later for
      cardiac function evaluation by cardiac magnetic resonance imaging. RESULTS: The
      IGF-1/HGF activated c-kit positive-CD45 negative epCSCs and increased their
      myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner,
      improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive
      hypertrophy. It significantly increased c-kit positive-CD45 negative epCSC number
      and fostered the generation of new myocardium (myocytes and microvasculature) in
      infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF
      1/HGF reduced infarct size and improved left ventricular function at 2 months
      after AMI. CONCLUSIONS: In an animal model of AMI relevant to the human disease,
      intracoronary administration of IGF-1/HGF is a practical and effective strategy
      to reduce pathological cardiac remodeling, induce myocardial regeneration, and
      improve ventricular function.

PMID- 21723062
TI  - Acute aortic occlusion from a Candida fungus ball.
AB  - Fungal arterial infections are well-described entities resulting in direct
      invasion of the arterial wall or embolic occlusion of small and medium-sized
      arteries. However, acute occlusion of large vessels such as the aorta by fungal
      material is exceedingly rare. A 53-year-old woman presented with acute bilateral
      lower extremity ischemia. She had a history of fungal endocarditis requiring two
      prosthetic mitral valve replacements; the last episode was 7 months before the
      current admission. Imaging studies revealed that she had an acute infrarenal
      aortic occlusion, with evidence of multiple end-organ emboli. After transfemoral
      thromboembolectomy, perfusion was restored to her lower extremities with minor
      neurologic sequelae. She ultimately responded to intravenous antifungal agents.

PMID- 21723063
TI  - Mycotic aneurysm of the thoracoabdominal aorta in a child with end-stage renal
      disease.
AB  - A 5-year-old child with nephrotic syndrome developed a mycotic saccular
      thoracoabdominal aortic aneurysm (TAAA) involving the visceral segment within a 4
      month period following pneumococcal bacteremia and presumed spontaneous bacterial
      peritonitis (SBP). Due to continued aneurysm growth and progression to end-stage
      renal disease, TAAA repair was performed, followed by cadaveric kidney
      transplantation. This is the first known instance of mycotic aortic aneurysm
      formation as a consequence of SPB and the first report of TAAA repair in
      preparation for kidney transplantation in a child.

PMID- 21723064
TI  - Randomized clinical trial of open-cell vs closed-cell stents for carotid stenting
      and effects of stent design on cerebral embolization.
AB  - OBJECTIVE: The effect of stent design on cerebral embolization has not been
      established. The purpose of this trial was to contrast the incidence of
      subclinical cerebral embolization in high-risk patients undergoing carotid artery
      stenting (CAS) with open-cell vs closed-cell stents. METHODS: During an 18-month
      period, 40 patients were randomized (1:1) to undergo CAS with open-cell
      (Acculink, n = 20) or closed-cell stents (Xact, n = 20). A single filter device
      for embolic protection (Accunet filter) was used. Transcranial Doppler (TCD)
      detected microembolic signals (MES) during CAS and preprocedural and 24-hour
      postprocedural diffusion-weighted magnetic resonance imaging (DW-MRI) were used
      to determine cerebral embolization. Univariate and nonparametric analyses were
      used to assess associations between stent design and cerebral embolization.
      RESULTS: CAS was performed in 17 symptomatic patients (43%) and 23 asymptomatic
      patients (57%) with a similar number of open-cell and closed-cell stents (9/8 and
      11/12, respectively). The total and poststenting median ipsilateral MES counts
      detected by TCD were 264 (interquartile range [IQR], 222-343) and 48 (IQR, 41-66)
      for open-cell stents and 339 (IQR, 163-408) and 53 (IQR, 23-88) for closed-cell
      stents, respectively (P > .56). New acute cerebral emboli detected with DW-MRI
      occurred in 53% and 47% of patients undergoing CAS with open-cell and closed-cell
      stents, respectively (P = 1.0). The total and ipsilateral median numbers of DW
      MRI lesions between groups were not statistically significantly different (ie, 2
      [IQR, 0-4] and 1 [IQR, 0-3] for open-cell stents and 1 [IQR, 0-3] and 1 [IQR, 0
      2] for closed cell-stents, respectively; P > .4). One asymptomatic patient
      undergoing CAS with an open-cell stent sustained a minor stroke; the 30-day
      stroke-death rate in this series was 2.5%. CONCLUSION: Cerebral embolization, as
      detected by TCD and DW-MRI, occurs with similar frequency after CAS with open
      cell and closed-cell stents. This randomized trial does not support the
      superiority of any stent design with respect to cerebral embolization.

PMID- 21723065
TI  - The epidemiology of subclavian artery calcification.
AB  - OBJECTIVES: The purpose of the present study was to determine the prevalence and
      risk factor associations for subclavian artery calcification. BACKGROUND:
      Arterial calcification is a marker of atherosclerosis, and its presence portends
      an adverse prognostic risk. The prevalence and associated risk factors for aortic
      arch, carotid, renal, and coronary calcification have been well described. Fewer
      data are available for subclavian artery calcification. METHODS: Electron-beam
      computed tomography was used to evaluate the extent of vascular calcification in
      multiple arterial beds in 1387 consecutive individuals who presented for
      preventive medicine services at a university-affiliated disease prevention
      center. Laboratory values for blood pressure, lipids, anthropomorphic data, and
      self-reported medical history were obtained. RESULTS: Subclavian artery
      calcification was present in 439 of 1387 individuals (31.7%). Those with
      subclavian artery calcification were significantly older, had a smaller body mass
      index, and were more likely to also have calcification of nonsubclavian vascular
      beds. When adjusted for cardiovascular disease risk factors, the presence of
      subclavian artery calcification was significantly associated with age (prevalence
      ratio [PR], 1.04; P < .001), hypertension (PR, 1.20; P = .01), history of smoking
      (PR, 1.21; P = .01), and calcification in nonsubclavian vascular beds (PR, 1.58;
      P = .01). Subclavian artery calcification was also associated with an increased
      pulse pressure (beta-coefficient = 2.2, P = .008). CONCLUSIONS: Subclavian artery
      calcification is relatively common and is significantly associated with age,
      smoking, hypertension, and nonsubclavian vascular calcification. There may be a
      relationship between vascular stiffness, as manifested by a widened pulse
      pressure, and the presence of subclavian artery calcification.

PMID- 21723066
TI  - Sleep-induced amaurosis fugax.
AB  - Amaurosis fugax is a manifestation of retinal ischemia, commonly described in the
      setting of carotid atherosclerotic disease. Thromboembolic, and less frequently,
      hemodynamic mechanisms have been described as responsible for producing negative
      symptoms of transient monocular vision loss during periods of wakefulness. We
      report an unusual presentation in which the patient became symptomatic during
      sleep. Initially, photopsias-positive symptoms were experienced, which caused the
      patient to awaken; this was immediately followed by transient monocular vision
      loss. Carotid endarterectomy was curative.

PMID- 21723067
TI  - A natural history of aortic aneurysm hygroma.
AB  - A 56-year-old man with a family history of aortic aneurysm underwent routine
      repair in 2003. A postoperative computed tomography scan showed a 6-cm perigraft
      hygroma. Sudden onset of abdominal pain 12 months later revealed a larger
      hygroma, with an additional anterior fluid collection suggestive of contained
      rupture. The bilobed hygroma remained stable until 2010, when he presented with
      chills and severe abdominal pain. A computed tomography scan demonstrated free
      rupture of the sister hygroma, with air pockets observed within the sac.
      Conservative management was elected. Air pockets as well as the hygroma
      eventually resolved, and the patient remains well.

PMID- 21723068
TI  - Long-term impact of a preclinical endovascular skills course on medical student
      career choices.
AB  - OBJECTIVE: Surging interest in the 0 + 5 integrated vascular surgery (VS)
      residency and successful recruitment of the top students in medical school
      requires early exposure to the field. We sought to determine the impact of a high
      fidelity simulation-based preclinical endovascular skills course on medical
      student performance and ultimate career specialty choices. METHODS: Fifty-two
      preclinical medical students enrolled in an 8-week VS elective course from 2007
      to 2009. Students completed a baseline and postcourse survey and performed a
      renal angioplasty/stent procedure on an endovascular simulator (pretest). A
      curriculum consisting of didactic teaching covering peripheral vascular disease
      and weekly mentored simulator sessions concluded with a final graded procedure
      (posttest). Long-term follow-up surveys 1 to 3 years after course completion were
      administered to determine ultimate career paths of participants as well as
      motivating factors for career choice. RESULTS: Objective and subjective
      performance measured on the simulator and through structured global assessment
      scales improved in all students from pre- to posttest, particularly with regard
      to technical skill and overall procedural competency (P < .001). Prior to
      enrolling in the course, 9% of the students expressed high interest in VS, and
      after completing the course, this response nearly tripled in terms of seriously
      considering VS as a career option (P = .03). Overall interest postcourse in VS
      and procedural-based surgical specialties was nearly 90%. In long-term follow-up,
      25% were still strongly considering integrated VS residencies, with other top
      career choices including surgical subspecialties (64%), radiology (10%), and
      cardiology (6%). Most respondents indicated major reasons for continued interest
      in VS were the ability to practice endovascular procedures on the simulator (92%)
      and mentorship from VS faculty (70%). CONCLUSIONS: Basic endovascular skills can
      be efficiently introduced through a simulation-based curriculum and lead to
      improved novice performance. Early exposure of preclinical medical students
      provides an effective teaching and recruitment tool for procedural-based fields,
      particularly surgical subspecialties. Mentored exposure to endovascular
      procedures on the simulator positively impacts long-term medical student
      attitudes toward vascular surgery and ultimate career choices.

PMID- 21723070
TI  - Thrombolysis for lower extremity bypass graft occlusion.
AB  - BACKGROUND: Thrombolysis is a common method in the treatment of lower extremity
      bypass graft occlusion. The purpose of this study was to investigate the results
      of thrombolytic therapy in the management of acute bypass graft occlusion and to
      identify risk factors for technical failure and amputation. METHODS: All patients
      at two tertiary referral centers undergoing thrombolysis for acute graft
      occlusion in the lower limb between January 1, 2000 and December 31, 2008 were
      retrospectively reviewed. Factors associated with technical failure of
      thrombolytic therapy, major amputation, and mortality were determined with
      multivariate analysis, and long-term outcomes were assessed with the Kaplan-Meier
      method and log-rank test. RESULTS: During the study period, 123 patients
      underwent thrombolysis for acute bypass graft occlusion. Mean age was 69 years
      (range, 27-91 years); 38% were women. Sixty-seven percent had synthetic grafts.
      Acute critical leg ischemia (74%) was the dominating symptom preceding
      thrombolytic treatment. In 29% of cases, no adjunctive interventions were
      required, whereas 21% underwent open surgery, 39% endovascular intervention, and
      11% underwent a hybrid procedure. Technical failure of thrombolysis occurred in
      18 patients. Presence of ischemic heart disease (P = .013), older grafts (P =
      .014), and synthetic grafts (trend; P = .092) were associated with success of
      thrombolysis, and ischemic heart disease remained as an independent factor in the
      multivariate analysis for technical success of thrombolysis (P = .04; odds ratio
      4.0; 95% confidence interval [CI; 1.1-15.1]), whereas there was a trend for older
      grafts (P = .089). Mean follow-up was 38 months (range, 0-119 months). The major
      amputation rate was 11% (14/123) at 1 month and 25% (31/122) at 1 year. In a Cox
      regression model, technical failure (P = .031; hazard ratio [HR] 2.58, 95% CI
      [1.0-6.08]), higher age (P = .004; HR 1.06, 95% CI [1.02-1.10]), and synthetic
      graft as opposed to vein graft (P = .050; HR 2.63, 95% CI [1.0-6.9]) remained as
      independent factors associated with major amputation. The amputation-free
      survival rate was 89% and 75% at 1 and 12 months, respectively. Higher age (P <
      .001; HR 1.06, 95% CI [1.03-1.09]) and acute limb ischemia (P = .007; HR 2.40,
      95% CI [1.26-4.56]) remained as independent adverse factors associated with
      amputation-free survival. CONCLUSIONS: Our findings support the use of
      thrombolysis in the treatment of acute bypass graft occlusion in the lower limb
      given its acceptable short- and long-term amputation-free survival rates.
      Technical failure and higher age were factors associated with major amputation.
      Synthetic grafts appeared to have a somewhat increased likelihood of technically
      successful thrombolysis compared with vein grafts, but on the other hand, they
      exhibited an increased risk of amputation during follow-up.

PMID- 21723069
TI  - Results of endovascular aortic aneurysm repair with general, regional, and
      local/monitored anesthesia care in the American College of Surgeons National
      Surgical Quality Improvement Program database.
AB  - BACKGROUND: This study examined outcomes of endovascular repair of infrarenal
      abdominal aortic aneurysms (EVAR) using general, spinal, epidural, and
      local/monitored anesthesia care (MAC) in a multicenter North American hospital
      database reflecting contemporary anesthesia and surgical practices. METHODS:
      Elective EVAR cases performed between 2005 and 2008 were identified from the
      American College of Surgeons National Surgical Quality Improvement Program
      database using Current Procedural Terminology codes. Excluded were emergency
      cases and patients with concomitant procedures requiring general anesthesia.
      Patient-level comorbidities, characteristics, and intraoperative and
      postoperative details were examined. Complications were analyzed individually and
      in aggregate categories, including wound, pulmonary, renal, venous
      thromboembolic, cardiovascular, operative, and septic. Length of stay (LOS) and
      30-day mortality were examined. Characteristics and outcomes were described using
      mean +/- standard deviation or count (%), and comparisons were evaluated for
      statistical significance using chi(2), Fisher exact test, and univariate linear
      regression. LOS was analyzed with linear regression techniques using a log
      transformation. Associations between anesthesia type and outcomes were examined
      using univariable and multivariable regression techniques. RESULTS: We identified
      6009 elective EVAR procedures for analysis. General anesthesia was used in 4868
      cases, spinal anesthesia in 419, epidural anesthesia in 331, and local/MAC in
      391. Defined morbidity occurred in 11% of patients. Median LOS was 2
      (interquartile range, 1-3) days, and mean LOS was 2.8 +/- 4.3 days. The 30-day
      mortality rate was 1.1%. Significant multivariate associations were observed
      between anesthesia type, pulmonary morbidity, and log-LOS. General anesthesia was
      associated with an increase in pulmonary morbidity vs spinal (odds ratio [OR],
      4.0; 95% confidence interval [CI], 1.3-12.5; P = .020) and local/MAC anesthesia
      (OR, 2.6; 95% CI, 1.0-6.4; P = .041). Use of general anesthesia was associated
      with a 10% increase in LOS for general vs spinal anesthesia (95% CI, 4.8%-15.5%;
      P = .001) and a 20% increase for general vs local/MAC anesthesia (95% CI, 14.1%
      26.2%; P < .001). Trends toward increased pulmonary morbidity and LOS were not
      observed for general vs epidural anesthesia. No significant association between
      anesthesia type and mortality was observed. CONCLUSIONS: In contemporary North
      American anesthetic and surgical practice, general anesthesia for EVAR was
      associated with increased postoperative LOS and pulmonary morbidity compared with
      spinal and local/MAC anesthesia. These data suggest that increasing the use of
      less-invasive anesthetic techniques may limit postoperative complications and
      decrease the overall costs of EVAR.

PMID- 21723071
TI  - Comparable mortality with open repair of complex and infrarenal aortic aneurysm.
AB  - BACKGROUND: A consequence of endovascular aneurysm repair (EVAR) of anatomically
      straightforward infrarenal abdominal aortic aneurysm repair cohort (AAA) is that
      open aneurysm repair is more commonly performed for complex anatomy. Complex
      aneurysm repair with visceral vessel involvement (CAA) or combined aneurysm
      repair and visceral vessel reconstruction (VVR) has traditionally been considered
      to increase morbidity and mortality compared with repair of infrarenal AAA. This
      study evaluated contemporary outcomes of open abdominal aneurysm surgery,
      including AAA, CAA, and VVR using the National Surgical Quality Improvement
      Program (NSQIP) database. METHODS: The NSQIP Participant Use File was queried by
      CPT code to identify patients undergoing AAA, CAA, and VVR (2005-2008).
      Comparative analysis of clinical features, technical details and 30-day outcomes
      was performed using univariate methods. Logistic regression analysis was used to
      identify predictors of morbidity and mortality. RESULTS: A total of 2820 patients
      underwent AAA and 592 CAA. Renal insufficiency (ie, creatinine >1.4 mg/dL) rates
      were similar in AAA and CAA patients, however, more frequent in patients with VVR
      (51% vs 31% [no bypass]; P < .01). CAA was less likely to be performed urgently
      (6.3% vs 9.1%; P < .05) and was associated with increased operative time (254 +/-
      100 vs 224 +/- 93; P < .01) compared with AAA. Univariate analysis showed that
      CAA did not increase mortality (5.7% vs 5.1%; P = .5). CAA slightly increased
      overall complications (32% vs 27%; P = .01) compared with AAA. 73 (2.5%) AAA and
      84 (12%) CAA patients had simultaneous VVR and these patients exhibited a trend
      toward increased mortality (8.9% vs 5.2%; P = .07). VVR increased complications
      (43% (VVR) vs 26% [no bypass]; P < .01), including ventilation >48 hours (21%
      [VVR] vs 12% [no bypass]; P < .01), renal failure (7.6% [VVR] vs 4.1% [no
      bypass]; P = .04), and sepsis (13% [VVR] vs 6.3% ([no bypass]; P < .01).
      Multivariate analysis demonstrated that CAA (odds ratio [OR], 1.3 [95% confidence
      interval (CI), 1.1-1.6]; P = .01) and VVR (OR, 2.2 [95% CI, 1.8-3.6]; P < .01)
      increased the odds of any complication. Independent predictors of mortality
      included dependent functional status (OR, 3.6 [95% CI, 2.3-5.4]; P < .01),
      elevated pre-op creatinine (OR, 2.9 [95% CI, 2.2-4.0]; P < .01), type II diabetes
      (OR, 1.6 [95% CI, 1.05-2.4]; P = .03), and age (OR, 1.06 [95% CI, 1.03-1.08]; P <
      .01). Neither CAA (OR, 1.2 [95% CI, 0.84-1.8]; P = .3) nor VVR (OR, 1.6 [95% CI,
      0.89-2.9]; P = .11) were associated with increased mortality compared with AAA.
      CONCLUSION: In contemporary practice the migration of open repair to increasingly
      complex cases has been achieved with 30-day mortality essentially equivalent to
      open repair of infrarenal AAA. Patients who require VVR do sustain increased
      complications, in particular renal failure. These data also emphasize the
      importance of baseline renal insufficiency in clinical decision making. CAA and
      VVR are associated with increased morbidity in comparison to AAA repair; however,
      both procedures can be safely performed in patients without increased risk of
      operative mortality.

PMID- 21723072
TI  - The influence of thrombus, calcification, angulation, and tortuosity of
      attachment sites on the time to the first graft-related complication after
      endovascular aneurysm repair.
AB  - PURPOSE: Endovascular aneurysm repair (EVAR) is associated with high graft
      related complication rates during follow-up. Anatomical fit between patient and
      endograft could be an important factor for successful treatment. Aim was to
      assess whether extent of thrombus, calcification, angulation, and tortuosity are
      associated with occurrence of complications after EVAR. MATERIALS AND METHODS:
      Patients in either United Kingdom EVAR trial 1 or 2 were included if they had
      undergone EVAR within 6 months of randomization and had a preoperative computed
      tomography (CT) scan of adequate quality in the core laboratory. Three
      dimensional CT imaging was used to assess extent of preoperative thrombus,
      calcification, angulation, and tortuosity in aneurysm neck and iliac segments.
      Cox regression modeling, adjusted for the variables tested and for known
      confounding variables, was used to investigate whether these factors were
      associated with increased rates of reported first complications. RESULTS: A total
      of 217 patients with 53 first graft-related complications were analyzed after a
      mean follow-up of 3.6 years. Adjusted hazard ratios (95% confidence intervals, P
      values) for complications per unit increase of variable were 0.96 (0.92-0.99,
      0.018) for neck thrombus, 1.06 (1.00-1.12, 0.044) for neck calcification, 1.02
      (1.00-1.05, 0.079) for neck angulation, 1.04 (1.01-1.06, 0.011) for common iliac
      thrombus, 0.96 (0.93-1.00, 0.033) for common iliac calcification, and 5.96 (1.53
      23.28, 0.010) for common iliac tortuosity. CONCLUSION: Increased neck angulation
      and calcification and common iliac thrombus and tortuosity are associated with
      higher rates of graft-related complications after EVAR. Increased neck thrombus
      and common iliac calcification appear to protect against complications. Careful
      evaluation of these factors prior to EVAR might lead to lower complication rates.

PMID- 21723073
TI  - Brachiocephalic venous aneurysm with unusual clinical observations.
AB  - Thoracic venous aneurysm is an extremely rare condition. This report describes
      the case of a 70-year-old woman with a left brachiocephalic venous aneurysm that
      caused recurrent nerve paralysis. Contrast-enhanced computed tomography and
      venography revealed a venous aneurysm, 4 cm in size, located adjacent to the
      venous angle. Anticoagulation therapy was started, and 1-1/2 months later, the
      aneurysm greatly decreased in size and showed marked calcification along its
      periphery. Venous aneurysms that shrink after anticoagulation therapy are
      exceptionally rare. The clinical features of this condition have been briefly
      reviewed.

PMID- 21723074
TI  - Low rehospitalization rate for vascular surgery patients.
AB  - OBJECTIVES: Reducing rehospitalization rates has been proposed to improve care,
      reduce costs, and as a pay-for-performance criterion. Recent review of Medicare
      claims data indicates that vascular surgery patients have among the highest rates
      of 30-day rehospitalization at 23.9%. METHODS: We retrospectively examined all
      live patient discharges (n = 799) from the vascular surgery service at a single
      university hospital over 12 months. Planned and unplanned 30-day
      rehospitalizations were distinguished, and predictors of unplanned 30-day
      rehospitalization were determined. To identify whether patients were readmitted
      to other hospitals, a prospective study of patient discharges (n = 66) over 1
      month was also performed. RESULTS: Ninety-five (11.9%) of the 799 patient
      discharges from the vascular surgery service were rehospitalized within 30 days.
      Of these, 71 were unplanned; therefore, the unplanned rehospitalization rate was
      8.9%. The most common causes of unplanned 30-day rehospitalization were related
      to wound complications. Diabetes (P = .039) predicted unplanned 30-day
      rehospitalization by multivariate analysis. Patients with the diagnosis of
      critical limb ischemia (14.9%) and patients undergoing open lower extremity
      revascularization (14.6%) had the highest rates of unplanned 30-day
      rehospitalization. In the prospective portion of this study, no patient was
      readmitted to any other hospital. CONCLUSIONS: Relatively low 30-day
      rehospitalization was accomplished in vascular surgery patients at a single
      university hospital. Moreover, planned rehospitalizations accounted for
      approximately 25% of readmissions in vascular surgery patients. Strategies
      designed to reduce rehospitalization in diabetics may be warranted.

PMID- 21723075
TI  - Treatment of an ilioenteric fistula with an Amplatzer Vascular Plug.
AB  - Arterioenteric fistulae often present a diagnostic and therapeutic dilemma for
      physicians. Traditional therapy consists of open repair, which is often poorly
      tolerated by patients. As a consequence, endovascular repair, consisting
      primarily of stent graft exclusion, has been attempted by some as a less invasive
      approach. We report a patient with an ilioenteric fistula in which hemorrhage was
      successfully treated with an Amplatzer Vascular Plug (AGA Medical Corporation,
      Plymouth, Minn).

PMID- 21723076
TI  - Relationship between ankle brachial index and arterial remodeling in
      pseudoxanthoma elasticum.
AB  - OBJECTIVES: Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease
      characterized by elastic fiber fragmentation and calcification in the cutaneous,
      ophthalmologic, and vascular tissues. Cardiovascular manifestations such as
      peripheral arterial disease (PAD) are frequent in PXE. Because of the changes in
      the elastic properties and medial calcification of the arterial wall in PXE, the
      impact of the arterial remodeling on the ankle brachial index (ABI), a well
      established diagnostic method for the detection and follow-up of PAD, remains to
      be determined in this disease. METHODS: This was a cross-sectional, comparative,
      open study, which took place at the PXE Consultation Center, University Hospital
      of Angers. The subjects were 53 patients (mean age, 49 +/- 14 years; 35 females)
      with PXE clinically proven on the basis of established criteria (skin changes,
      angioid streaks, and skin biopsy). The ABI at rest, symptoms of intermittent
      claudication (IC), carotid intima-media thickness (IMT), carotid-femoral pulse
      wave velocity (c-f PWV), compliance (CC), and beta stiffness index were measured
      in a single-center cohort. RESULTS: Forty-five percent of the PXE patients had an
      ABI <=0.90, but only one patient had an ABI >1.40. IC was found in 23% of the
      patients with an ABI <=0.90. There were no significant differences between the
      patients with a low and normal ABI in terms of IMT (P = .566) or beta stiffness
      index (P = .194), but differences were significant for c-f PWV (P = .010) and CC
      (P = .011). Adjusted multivariate linear regression for the Framingham-Laurier
      score showed that patients with a low ABI had less compliant carotid arteries (B
      = 0.318, P = .039). CONCLUSIONS: PAD detected by a low ABI is very frequent in
      PXE, although with limited prevalence of symptomatic claudication. Unexpectedly,
      ABI was low in such calcifying PAD and associated with lower CC, independently of
      atherosclerosis risk factors. These findings demonstrate that PXE represents a
      unique monogenic model of PAD in which the specific arterial wall remodeling
      could change the diagnostic value of the ABI to detect PAD.

PMID- 21723077
TI  - [Transcutaneous aortic valve implantation: Anesthetic and perioperative
      management].
AB  - OBJECTIVE: To describe the perioperative management, from the point of view of
      the anesthesia-intensive care unit specialist, of patients with aortic stenosis
      who undergo transcatheter aortic valve implantation (femoral or apical TAVI).
      DATA SOURCE: The PubMed database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi)
      was queried, using the following keywords: aortic stenosis, transcatheter aortic
      valve implantation TAVI, outcome, complications, anesthesia. DATA SYNTHESIS: TAVI
      is performed in patients suffering from aortic stenosis and presenting with
      numerous comorbidities, high-predicted perioperative mortality and/or
      contraindications to conventional cardiac surgery. TAVI is performed either by
      percutaneous transfemoral or transapical puncture of the left ventricle (LV)
      apex. These patients are older, have more comorbidities than those undergoing
      aortic valve replacement surgery and perioperative mortality predicted by risk
      scores is higher. While transapical TAVI is performed with general anaesthesia,
      transfemoral TAVI can be performed with either general or locoregional
      anaesthesia and/or sedation. The choice of the anaesthetic technique for
      transfemoral TAVI depends on the patient's medical history, the technique chosen
      for valve implantation, the type of monitoring and the anticipated hemodynamic
      problems. The incidence of complications following TAVI is high, some are common
      to surgical aortic valve replacement, and others are specific to this technique.
      Because of the prevalence of comorbidities, the hemodynamic-specific constraints
      of this technique and the incidence of complications, anaesthetic and
      perioperative management (evaluation, anaesthetic technique, monitoring, post
      surgery care) requires the same level of expertise as in cardiac surgery
      anaesthesia. CONCLUSION: TAVI expands treatment options for patients with aortic
      valve stenosis. The anaesthesia team must be involved in the care of these
      patients with the same level of expertise and care as in heart surgery on
      critical patients.

PMID- 21723078
TI  - Antitumor effect of orlistat, a fatty acid synthase inhibitor, is via activation
      of caspase-3 on human colorectal carcinoma-bearing animal.
AB  - We established a HT-29/tk-luc human colorectal carcinoma-bearing animal model for
      the study of the inhibition effect and mechanism of orlistat, a fatty acid
      synthase (FASN) inhibitor. The results showed that orlistat caused cell cycle
      arrest at G1 phase, and triggered apoptosis through caspase-3 activation. The
      tumor inhibition effect of orlistat may also due to the inhibition of fatty acid
      synthesis without altering FASN activity. The tumor size of orlistat-treated mice
      in vivo was significantly smaller than that of the controls with 55% inhibition.
      The therapeutic efficacy was further confirmed with the bioluminescent imaging
      and nuclear molecular imaging with 131I-FIAU/gamma scintigraphy and 11C
      acetate/microPET. We suggest that FASN is a potential target for the treatment of
      human colorectal carcinoma.

PMID- 21723079
TI  - Short duration treatment in genotype 1 chronic hepatitis C patients with rapid
      virologic response to pegylated interferon plus ribavirin.
AB  - BACKGROUND: In patients with chronic hepatitis C, rapid HCV-RNA clearance under
      treatment might allow shorter treatment duration without modifying the sustained
      virological response (SVR) rate. This study evaluated the impact of rapid
      virological response (RVR) in HCV genotype 1b infection management. METHODS: In
      an open-label trial, 180 patients received standard doses of peginterferon alfa
      2a plus ribavirin. Those with undetectable serum HCV-RNA at week 6 (RVR) received
      24-week short-course treatment; patients with undetectable HCV-RNA at week 12
      (early responders [ER]) received 48-week "standard of care" treatment; patients
      with positive HCV-RNA at week 12 (non-responders [NR]) stopped the treatment.
      Study end-point was to determine SVR rate at week 24. RESULTS: The following
      responses were observed: 24% RVR, 44% ER, 32% NR. Among RVR subjects, HCV-RNA
      baseline levels and age were significantly lower (P=0.038 and 0.035 respectively)
      than in non-RVR patients. At follow-up, 91% of RVR and 33% of ER patients
      achieved SVR. Among those with RVR, patients experiencing post-therapy relapse
      were older than those who achieved a SVR (P=0.028). CONCLUSIONS: Chronic HCV-1b
      patients, achieving RVR with a 24-week treatment regimen, attained excellent SVR
      rates. In a cost-effective therapeutic approach, all HCV-1b patients eligible for
      therapy may have a short duration therapy on the basis of RVR.

PMID- 21723080
TI  - Possible role of peritoneal NF-kappaB in peripheral inflammation and cancer:
      lessons from the inhibitor DHMEQ.
AB  - NF-kappaB is a transcription factor and considered to be involved in the
      mechanisms of inflammation and cancer. We have designed the new NF-kappaB
      inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which directly binds to a
      specific cysteine residue of Rel family proteins to inhibit their DNA-binding
      activity. DHMEQ showed potent anti-inflammatory and anticancer activities in many
      animal models. So far DHMEQ has been administered mainly into the peritoneal
      cavity of animals. According to the limited distribution of DHMEQ in the
      peritoneal cavity after intraperitoneal administration, it is likely that NF
      kappaB in the peritoneal cells would be the main target of DHMEQ. Therefore, the
      inflammatory cells in the peritoneal cavity appear important for the regulation
      of peripheral inflammation and tumor growth in the body, and peritoneal NF-kappaB
      may be an important target for anti-inflammatory and anticancer agents in future.

PMID- 21723081
TI  - The action of Amblyomma cajennense tick saliva in compounds of the hemostatic
      system and cytotoxicity in tumor cell lines.
AB  - Ticks are blood-feeding arthropods that secrete anticoagulant molecules to
      maintain the fluidity of the blood during its feeding. Tick saliva has many
      compounds with biological activities that interact directly with host systems,
      such as blood clotting, platelet aggregation, cell death, among others. Some
      reports show that there are proteins with anticancer properties in tick saliva.
      This paper reports some of the biological roles of the Amblyomma cajennense tick
      saliva, including Factor Xa and thrombin inhibition, action on platelet
      aggregation, and also preliminary cytotoxic effects on tumor cell lines. The
      crude saliva was tested in the coagulation, fibrinolysis and platelet aggregation
      systems. The protein profile of the crude saliva was examined through anion
      exchange chromatography performed in a FPLC system. The chromatography separated
      seven protein fractions (Pools I to VII), which biological activities were
      evaluated. Moreover, the cytotoxic effects of the crude saliva were evaluated on
      SK-MEL-28 (melanoma cells) and MIA PaCa-2 (pancreas adenocarcinoma cells) using
      the MTT assay, flow cytometry and fluorescence microscopy. The crude saliva was
      able to induce cell death on both cancer cells lines, and, interestingly, the
      cytotoxic effects were not observed on human fibroblasts, which were used as
      control. The present work opens perspectives for the characterization and
      development of new molecules involved in the hemostatic system and in cancer
      control.

PMID- 21723082
TI  - Synergistic antitumoral effect of combination E gene therapy and Doxorubicin in
      MCF-7 breast cancer cells.
AB  - The low effectiveness of conventional therapies to achieve the long-term survival
      of metastatic breast cancer patients calls for the development of novel options.
      Genes encoding cytotoxic proteins have been proposed as a new strategy to enhance
      the antiproliferative activity of drugs. Combined therapy using these genes and
      classical antitumoral drugs are under intensive study. The E gene from phiX174
      encodes a membrane protein with a toxic domain that leads to a decrease in the
      tumour cell growth rate. With the aim of improving the anti-tumour effect on
      breast cancer cells of the currently used chemotherapeutic drugs (Paclitaxel,
      Docetaxel and Doxorubicin), we investigated the association of E suicide gene
      with these drugs. The effect of the combined therapy (gene therapy and cytotoxic)
      was determined by treating transfected MCF-7 cells and multicellular tumour
      spheroids (MTS) with drugs gradient concentrations. Our results showed that E
      gene has a direct oncolytic effect inducing a significant decrease in the
      proliferation rate of the MCF-7 cells. The E gene antitumoral activity was
      mediated by the induction of apoptosis (mitochondrial pathway). In addition, a
      significant enhancement of proliferation inhibition was observed when E gene
      transfection was associated with cytotoxic drugs in comparison to single
      treatments. The use of the combined therapy E gene-Doxorubicin obtained the
      greatest effect on the MCF-7 growth arrest. This therapeutic association also
      induced a significant enhancement of the MTS volume growth inhibition. Anti
      tumour activity of the chemotherapeutic drugs classically used in the treatment
      of breast cancer was enhanced by E gene. Our in vitro results indicate that
      experimental therapeutic strategy based in the combined therapy E gene and
      cytotoxic drugs may be of potential therapeutic value as a new strategy for
      patients with advanced breast cancer.

PMID- 21723083
TI  - [Pseudoseptical myositis ossificans in spinal cord injuried patients].
AB  - CONTEXT: Neurogenic myositis ossificans or para-osteo-arthropathy are part of
      heterotopic ossifications. They concern mostly spinal cord injured or cerebral
      injured patients. They mostly target the hip and can lead to local or general
      inflammatory signs which can mimic severe sepsis. We detail the frequent septic
      like symptomatology and the relevance of echography to make the diagnosis and to
      start adapted therapy. METHOD: We conducted a retrospective study from seven
      patients hospitalized in infectious disease department for suspicion of septical
      myositis and we compared this cohort with available data. RESULTS: They all have
      inflammatory syndrome and radiological signs. Diagnosis can be made early by
      echography, MRI or tomodensitometry. X-ray signs are delayed. CONCLUSION:
      Myositis ossificans can have a septical presentation but therapy is, at first,
      medical with non steroid anti inflammatory drugs and no antibiotic therapy.

PMID- 21723084
TI  - [Nonalcoholic fatty liver disease].
AB  - NAFLD encompasses a spectrum of liver diseases including simple steatosis and
      nonalcoholic steatohepatitis (NASH), which is characterized by inflammation and
      hepatocyte ballooning on a background of steatosis. NAFLD, the hepatic
      manifestation of the metabolic syndrome, has become one of the most common causes
      of chronic liver diseases over the last decade in developed countries as well as
      in low and middle-income regions owing to dramatic epidemic proportions of
      obesity and diabetes worldwide. While simple steatosis has mostly a benign
      course, NASH can lead to fibrosis, cirrhosis and hepatocellular carcinoma.
      Insulin resistance is considered as the cornerstone in the development of
      NAFLD/NASH. Liver biopsy remains the gold standard for the diagnosis of NASH.
      However, non-invasive markers of NASH and fibrosis represent interesting tools to
      identify patients with severe liver injuries. Even if insulin sensitizers and
      hepatoprotective agents are promising drugs, no medication has been currently
      approved for the treatment of NASH. Diet, exercise and control of the metabolic
      disorders still represent crucial therapeutic options for the management of
      NAFLD/NASH.

PMID- 21723085
TI  - Re: two-stage exchange for infected resurfacing arthroplasty use of a novel
      cement spacer technique.

PMID- 21723086
TI  - Pseudotumor with dominant B-lymphocyte infiltration after metal-on-metal total
      hip arthroplasty with a modular cup.
AB  - We report a case of a patient who underwent metal-on-metal total hip arthroplasty
      with a modular cup and developed a pseudotumor 5 years postoperatively.
      Immunohistochemistry showed dominant B-lymphocyte infiltration in the
      periprosthetic tissue.

PMID- 21723087
TI  - Re: computer-assisted total knee arthroplasty for arthritis with extra-articular
      deformity.

PMID- 21723088
TI  - Re: common errors in the execution of preoperative templating for primary total
      hip arthroplasty.

PMID- 21723089
TI  - Total knee arthroplasty in patients with stiff knees.
AB  - The purpose of this study was to evaluate the clinical outcome of total knee
      arthroplasty and analyze the prognostic factors in patients with stiff knees.
      Thirty-two patients (39 knees) with severe knee arthritis and an arc of motion of
      50 degrees  or less were treated by total knee arthroplasty. The mean follow-up
      period was 58 months (range, 24-123 months). The mean arc of motion improved from
      35 degrees  before the operation to 94 degrees  at the time of the latest follow
      up (P<.05). Improvement in knee motion after postoperative 3 months was
      insignificant. The most important factor related to the final arc of knee motion
      was preoperative arc of knee motion. The V-Y quadricepsplasty was associated with
      an inferior clinical outcome. Total knee arthroplasty in patients with stiff
      knees has substantially improved in the clinical outcome and the arc of motion.

PMID- 21723090
TI  - Computer-assisted detection of infectious lung diseases: a review.
AB  - Respiratory tract infections are a leading cause of death and disability
      worldwide. Although radiology serves as a primary diagnostic method for assessing
      respiratory tract infections, visual analysis of chest radiographs and computed
      tomography (CT) scans is restricted by low specificity for causal infectious
      organisms and a limited capacity to assess severity and predict patient outcomes.
      These limitations suggest that computer-assisted detection (CAD) could make a
      valuable contribution to the management of respiratory tract infections by
      assisting in the early recognition of pulmonary parenchymal lesions, providing
      quantitative measures of disease severity and assessing the response to therapy.
      In this paper, we review the most common radiographic and CT features of
      respiratory tract infections, discuss the challenges of defining and measuring
      these disorders with CAD, and propose some strategies to address these
      challenges.

PMID- 21723091
TI  - Renal glomerular and tubular injury after gastric bypass in obese rats.
AB  - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) surgery is the most common surgical
      intervention for long-term weight loss in morbidly obese patients. By decreasing
      obesity-associated hyperfiltration, diabetes, and hypertension, RYGB is touted to
      stabilize, if not prevent, progression of chronic renal disease. To test this,
      the renal histology of diet-induced obese rats that underwent RYGB surgery was
      compared with that of pair-fed and sham obese controls. METHODS: Sprague-Dawley
      rats, fed a high-fat, low-oxalate diet to induce gross obesity, were randomized
      to RYGB (n = 6), gastrointestinal-intact sham-operated obese controls (sham, n =
      4), or gastrointestinal-intact sham-operated obese pair-fed controls (fed, n =
      8). Daily body weight and food intake were recorded. On postoperative day 42,
      renal histology and immunohistochemistry were examined. Renal pathology was
      assessed by a categorical glomerular lesion score and a quantitative
      glomerular/tubular scoring system by experienced veterinary pathologists.
      Osteopontin and ED-1 (monocyte/macrophage cell) stainings were estimated by the
      percentage of stained area and the number of counted cells/high-power field,
      respectively. RESULTS: Compared with sham and fed controls, RYGB rats had
      significant decreases in body weight (P < 0.001), more glomerular lesions (P =
      0.02), and received higher glomerular and tubular lesion scores (P < 0.01). RYGB
      rodents had significantly stronger staining for osteopontin within the inner
      medullary region (P < 0.005) and ED-1 within the outer medullary region (P <
      0.02) compared with sham and fed controls. CONCLUSION: In this diet-induced obese
      rat model, RYGB is associated with chronic glomerulosclerosis and
      tubulointerstitial nephritis, confirmed by histology and immunohistochemistry.
      Prospective studies to better define the injurious mechanisms in this model are
      underway.

PMID- 21723092
TI  - Replication of ancient Egyptian osteotomies of the facial skeleton: insights into
      the mummification process.
AB  - A recent radiographic study of an Egyptian mummified head from the Middle Kingdom
      revealed methodical mutilations of the facial skeleton that were performed after
      death and prior to wrapping the corpse for burial. These mutilations consisted of
      removal of the coronoid processes of the mandible and portions of the zygomas
      presumably via an intraoral approach. They are unique in the archaeological
      record. The authors hypothesize that the procedures were carried out to
      facilitate jaw opening and may be related to a ritual known as the 'Opening of
      the Mouth' ceremony. The purpose of this study was to demonstrate the feasibility
      of performing these remarkable osteotomies on two human cadavers using
      instruments similar to those available to the ancient embalmer. Bilateral
      osteotomies of the zygomas and coronoid processes were carried out transorally
      and the bones removed. Pre- and postoperative maximal incisal opening measured 25
      mm and 53 mm, respectively. Postoperative high-resolution computed tomographic
      (CT) scans were obtained. Comparison of the postoperative cadaver and mummy CT
      scans demonstrate remarkable similarity between the resections. Results of this
      study demonstrate that the ancient skeletal mutilations could have been performed
      transorally during the mummification process and would have enhanced jaw opening.

PMID- 21723093
TI  - Marked strain and substrain differences in induction of status epilepticus and
      subsequent development of neurodegeneration, epilepsy, and behavioral alterations
      in rats. [corrected].
AB  - Outbred rat strains such as Sprague-Dawley (SD) or Wistar are widely used in
      epilepsy models, including popular models of temporal lobe epilepsy in which
      spontaneous recurrent seizures (SRS), hippocampal damage, and behavioral
      alterations develop after status epilepticus (SE). Such rats are randomly
      outbred, hence allelic variations can occur across separate colonies, so that
      outbred rats from different sources may have little in common with each other
      besides their names and similarities in pelage. Although such intrastrain
      differences may be an important reason for discrepancies between studies from
      different laboratories, the extent to which such differences affect development
      of seizures, neurodegeneration, and psychopathology in post-SE models of epilepsy
      has received little attention as yet. In the present study, we induced SE by
      sustained electrical stimulation of the basolateral amygdala in SD and Wistar
      rats from different breeders (Harlan, Charles River, Janvier, Taconic) as well as
      different breeding locations of the same breeder (Harlan-Winkelmann in Germany
      vs. Harlan in the Netherlands). Several marked inter- and intrastrain differences
      in induction of SE and its long-term consequences were found. Wistar rats from
      different vendors were all strikingly less sensitive to SE induction than SD rats
      from Harlan-Winkelmann or Harlan. Within the SD strain, SD rats from Charles
      River exhibited markedly lower sensitivity to SE induction than all other groups
      of SD rats. The majority of SD rats from different vendors developed SRS after SE
      except SD rats from Charles River. The latter rats also markedly differed in
      basal behavior, SE-induced behavioral alterations and neurodegeneration from
      other SD substrains. These marked inter- and intrastrain differences provide an
      interesting tool to study the impact of genetic and environmental factors on
      seizure susceptibility, epileptogenesis, and the relationship between behavior
      and epilepsy and vice versa.

PMID- 21723094
TI  - Neuromagnetic cerebellar activation during seizures arising from the motor
      cortex.
AB  - We utilized the high temporal resolution, whole head coverage and novel analysis
      methodology of magnetoencephalography (MEG) to record the dynamics of cerebellar
      activation during focal motor seizures. We analyzed ictal MEG data from a four
      year old using an event-related beamformer to localize and display ictal changes
      over the motor cortex and cerebellum. Contralateral activation of the cerebellum
      was seen 14s after MEG ictal onset over the motor cortex. These findings
      represent the first indication of ictal activity within the cerebellum in humans,
      measured non-invasively with MEG.

PMID- 21723095
TI  - Differences in automated analyzers for assessing the use of imprecise serum
      chloride concentrations as indirect predictors of serum bromide concentrations.
AB  - Although bromide (Br) is used to treat intractable epilepsy, serum Br
      concentrations are not routinely analyzed. The present study measured serum Br(-)
      and Cl(-) concentrations in Br-treated epileptic patients, showing a significant
      correlation between Br(-) and imprecise Cl(-) concentrations, which suggested the
      use of a unique correlating equation for each diagnostic tool. Results indicated
      that imprecise Cl(-) concentrations are useful markers for measuring appropriate
      serum Br(-) levels in epileptic patients.

PMID- 21723096
TI  - D-cycloserine facilitation of cognitive behavioral therapy for delusions in
      schizophrenia.
AB  - Glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction has been proposed
      as a mechanism underlying psychosis. D-cycloserine, a partial agonist at the
      glycine site of the NMDA receptor, enhances learning in animal models, although
      tachyphylaxis develops with repeated dosing. Once-weekly dosing of D-cycloserine
      produces persistent improvement when combined with cognitive behavioral therapy
      (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a
      learning deficit, characterized by the failure to use contradictory evidence to
      modify the belief. CBT techniques have been developed with modest success to
      facilitate such reality-testing (or new learning) in delusional beliefs. The
      current study evaluated whether D-cycloserine could potentiate beneficial effects
      of CBT on delusional severity. Twenty-one outpatients with schizophrenia or
      schizoaffective disorder and moderately severe delusions were randomized in a
      double-blind cross-over design to receive a single-dose of either D-cycloserine
      50mg or placebo in a counterbalanced order on two consecutive weeks 1h prior to a
      CBT intervention involving training in the generation of alternative beliefs.
      Assessments were completed at baseline, 7 days following the first study drug
      administration and 7 days following the second study drug administration.
      Contrary to prediction, there was no significant d-cycloserine treatment effect
      on delusional distress or severity as measured by the SAPS or PSYRATS. An
      unexpected finding was an order effect, whereby subjects who received D
      cycloserine first had significantly reduced delusional severity, distress, and
      belief conviction on PSYRATS compared to subjects who received placebo first.
      However, this finding is consistent with animal models in which D-cycloserine
      enhances learning only when accompanying the first exposure to training.

PMID- 21723097
TI  - Disruption of tyrosinase glycosylation by N-acetylglucosamine and its
      depigmenting effects in guinea pig skin and in human skin.

PMID- 21723098
TI  - Factors involved in the level of functioning of patients with schizophrenia
      according to latent variable modeling.
AB  - PURPOSE: This study aimed at using latent variable modelling to explore the
      significantly contributing variables to functioning in schizophrenia patients.
      METHODS: The study cohort comprised 296 schizophrenia patients evaluated once for
      demographic characteristics, functioning (FROGS, SWN-K, QLS) and symptomatology
      (Positive and Negative Syndrome Scale [PANSS]). First exploratory multivariate
      analyses were conducted and then a model with functioning as a latent variable
      was proposed and tested with the data. RESULTS: Symptomatology as negative,
      cognitive and excitation factor are significant predictors of functioning
      assessed through FROGS (P<0.0001), SWN-K and QLS (P<0.001). The model was
      constructed with functioning defined as a latent variable, indicators are
      subscores on FROGS, SWN-K, QLS and exogenous variable included symptomatology,
      Duration of Untreated Psychosis (DUP) and educational level. CONCLUSION: Using
      the five clinical dimensions of the PANSS, (Positive, Negative, Cognitive,
      Anxiety/Depression and Excitation) the negative and cognitive dimensions are
      highly correlated via the latent variable to the three dimensions of functioning
      evaluated by the FROGS: "daily life", "social functioning" and "treatment" and
      the QLS subscores (interpersonnal, common object, instrumental role).
      Educationnal level is positively linked to functioning but not DUP. The model
      emphasizes the need for treatment strategies that have an effect on cognitive
      factors, to improve functioning in schizophrenia.

PMID- 21723099
TI  - Poly(D,L-lactide-co-glycolide)/hydroxyapatite core-shell nanospheres. Part 3:
      properties of hydroxyapatite nano-rods and investigation of a distribution of the
      drug within the composite.
AB  - A step-by-step analysis of the formation and the drug loading of the poly(D,L
      lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) composite was carried out in a
      perspective of the following parameters: the structure, the morphology and the
      adsorption/desorption properties of the composite's bioceramic part. The authors
      demonstrated the importance of the material's capacity to form a fine dispersion
      of solid HAp particles, as an initial step, for the further loading of the drug
      and for the formation of the core-shell structures. The nanometer-sized rods of
      HAp have the capacity of ensuring a rapid adsorption and a controlled desorption
      of the drug from their surface, and they can act as a nucleating site for the
      formation of polymeric cores. Each component of this material was labeled with
      fluorescence dye, which enabled an insight into the distribution of the
      components in the core-shells that were obtained as the final outcome. Such an
      analysis showed a high level of uniformity among the cores enclosed within
      polymeric shells. From a practical perspective, the labeling of each component of
      the composite can be regarded as an additional functionality of the material:
      labeling can enable us to monitor its action during the healing process. This
      ability to be easily detected is expected to enhance the procedure for the
      controlled delivery of antibiotics after their local implantation of carriers
      loaded with the antibiotic and to provide more careful control over this process.

PMID- 21723100
TI  - [Delayed diagnosis of newborn vitamin K deficiency bleeding: from simple
      cutaneous lesion to intracranial hemorrhage].

PMID- 21723101
TI  - [Long-term outcome of infliximab therapy in pediatric Crohn disease].
AB  - BACKGROUND: The efficacy of infliximab (IFX) in inducing and maintaining
      remission in pediatric Crohn disease is currently well documented. However, the
      optimal treatment strategy beyond 1 year has not been established. In particular,
      systematic continuation of maintenance therapy and its association with
      immunomodulators have not yet been analyzed. OBJECTIVE: The aim of this study was
      to describe the long-term outcome of pediatric Crohn disease patients on IFX
      therapy and to evaluate the clinical response to the therapy and the effect on
      growth. METHODS: A single-center and retrospective chart review was conducted.
      The clinical maintenance response to treatment, effect on the linear growth, and
      long-term outcome were examined. These parameters were analyzed according to the
      age of the patients, duration and localization of the disease, as well as
      associated therapies. RESULTS: We identified 52 children with Crohn disease
      younger than 16 years of age at the time of diagnosis. Of these patients, 20
      (38%) received a biologic therapy at a mean age of 13.9+/-2 years. Fifteen
      patients received IFX therapy and 13 (86%) were in clinical remission 10 weeks
      after the first infusion. Among the responders, 82% were still in remission after
      1 year of therapy and 66% after 2 years. Among patients treated for more than 1
      year, we observed IFX dependency in 89%. Thirty-eight percent of patients with
      initial IFX response showed a loss of response after a median of 30 months
      (range, 3-42 months). At 2 years, the median Z score for height among patients
      with presumed growth potential had improved slightly, from -0.7 to -0.55 DS. No
      serious adverse events were observed. CONCLUSION: Our results confirm the
      continuous efficacy of IFX in pediatric Crohn disease patients after 1 year of
      treatment. However, a high level of dependency was observed (89 %). A slight
      beneficial effect on growth was observed after 2 years of treatment.

PMID- 21723102
TI  - [Infectious complete atrioventricular block in children: 2 case reports].
AB  - We report 2 cases of children who developed a complete atrioventricular block
      following an infection, varicella without complication initially in the first
      case and Mycoplasma pneumoniae pneumopathy in the second case, in which a first
      degree congenital heart block was diagnosed on this occasion. In case 1, the
      treatment consisted in oral corticosteroids leading to the recovery of sinus
      rhythm; the course was unfavorable in the second case and required a permanent
      pacemaker. This cardiac complication of bacterial or viral infection is rare in
      children but evolves to permanent conduction disturbance in 1/3 of the cases. It
      is important to detect this disorder, which is feasible simply by a clinical
      examination and an electrocardiogram.

PMID- 21723103
TI  - [Spontaneous regression of a giant facial hemangioma].
AB  - Infantile cutaneous hemangioma is a benign vascular tumor and is very frequent in
      infants. The evolution is mostly favorable with spontaneous regression in 80% of
      cases. Clinical diagnosis is easy in its triphasic typical form with a phase of
      sometimes brutal postnatal growth, a phase of stabilization and a phase of slow
      secondary regression. We report a case of a giant facial hemangioma diagnosed at
      birth in full-term female newborn getting the right peri-orbital and fronto
      temporal region. Initial evolution was marked by a fast increase of the tumor
      justifying its stake under prednisone at the age of 3 months but without
      improvement. At the age of 6 months, the patient was hospitalized for infection
      of the hemangioma with favorable evolution under oxacilline. Following evolution
      was marked by the total regression of the hemangioma at the age of 5 years at the
      price of peri-orbital cutaneous scars. We discuss here the diagnostic,
      therapeutic and evolutionary aspects of this pathology and review of the
      literature.

PMID- 21723104
TI  - Wheelchair collaborative control for disabled users navigating indoors.
AB  - OBJECTIVE: Mobility is of key importance for autonomous living. Persons with
      severe disabilities may be assisted by robotic wheelchairs when manual control is
      not possible. However, these persons should contribute to control as much as they
      can to avoid loss of residual skills and frustration. Traditionally, wheelchair
      shared control approaches either give control to person or robot depending on the
      situation. METHODS AND MATERIALS: We propose a new shared control technique where
      robot and person contribute simultaneously to control. Their commands are
      weighted according to their respective local efficiencies and then combined via a
      reactive navigation strategy. Thus, assistance adapts to the user's needs. We
      refer to this approach as collaborative control. RESULTS: Collaborative control
      was tested in a home environment in Fondazione Santa Lucia (Rome) by 18
      volunteers presenting different degrees of physical and cognitive disability. All
      of them successfully finished a complex test path with assistance. Both users and
      caregivers' opinion on the system was very positive. Acceptance was very good
      according to the psychosocial impact of assistive devices scale. CONCLUSIONS:
      Collaborative control adapts to the person's needs and assists him/her when
      necessary, locally compensating any problem related to specific disabilities. An
      ANOVA returned a p-value of 0.016, meaning that there is significant improvement
      in task performance when collaborative control is used.

PMID- 21723105
TI  - Prioritized optimization in intensity modulated proton therapy.
AB  - In this work a prioritized optimization algorithm is adapted and applied to
      treatment planning for intensity modulated proton therapy (IMPT). Originally,
      this algorithm was developed for intensity modulated radiation therapy (IMRT)
      with photons. Prioritized optimization converts the clinical hierarchy of
      treatment goals into an effective optimization scheme for treatment planning. It
      presents an alternative to conventional methods that combine all optimization
      goals into a single optimization run with a weighted sum of all planning aims in
      the objective function. The highest order goal in the first step is to achieve a
      homogeneous dose distribution of the prescribed dose in the tumour. In subsequent
      steps the dose to organs at risk (OARs) is minimized dependent upon their
      clinical priority, whereby the results of previous steps are turned into hard
      constraints. The large number of degrees of freedom through the additional energy
      modulation of protons enables a better protection of OARs under the perpetuation
      of the prescribed dose in the planning target volume (PTV). The solution space of
      subsequent optimization steps can be extended by introducing a slip factor. This
      slip factor allows a slight deterioration of the homogeneity in the PTV compared
      to previous steps and entails much better results in IMRT planning. To
      investigate the relevance and necessity of the slip factor in IMPT, prioritized
      optimization with various slip factors is applied to a clinical patient case with
      a head and neck tumour. It emerges that in IMPT the slip factor has much less
      impact than in IMRT through the great number of degrees of freedom. Hence,
      prioritized optimization is particularly well suited for proton therapy planning.

PMID- 21723106
TI  - The search for stability on narrow supports: an experimental study in cats and
      dogs.
AB  - Kinematic and coordination variables were studied in two carnivorans, one with
      known locomotor capabilities in arboreal substrates (cat), and the other a
      completely terrestrial species (dog). Two horizontal substrates were used: a flat
      trackway on the ground (overground locomotion) and an elevated and narrow runway
      (narrow-support locomotion). Despite their different degree of familiarity with
      the 'arboreal' situation, both species developed a strategy to adapt to narrow
      supports. The strategy of cats was based on using slower speeds, coupled with
      modifications to swing phase duration, to keep balance on narrow supports. The
      strategy of dogs relied on high speeds to gain in dynamic stability, and they
      increased cycle frequency by reducing swing phase duration. Furthermore, dogs
      showed a high variability in limb coordination, although a tendency to canter
      like coordination was observed, and also avoided whole-body aerial phases. In
      different ways, both strategies suggested a reduction of peak vertical forces,
      and hence a reduction of the vertical oscillations of the centre of mass.
      Finally, lateral oscillation was reduced by the use of a crouched posture.

PMID- 21723107
TI  - The occurrence of chitin in the hemocytes of invertebrates.
AB  - The light-organ symbiosis of Euprymna scolopes, the Hawaiian bobtail squid, is a
      useful model for the study of animal-microbe interactions. Recent analyses have
      demonstrated that chitin breakdown products play a role in communication between
      E. scolopes and its bacterial symbiont Vibrio fischeri. In this study, we sought
      to determine the source of chitin in the symbiotic organ. We used a commercially
      available chitin-binding protein (CBP) conjugated to fluorescein to label the
      polymeric chitin in host tissues. Confocal microscopy revealed that the only
      cells in contact with the symbionts that labeled with the probe were the
      macrophage-like hemocytes, which traffic into the light-organ crypts where the
      bacteria reside. Labeling of extracted hemocytes by CBP was markedly decreased
      following treatment with purified chitinase, providing further evidence that the
      labeled molecule is polymeric chitin. Further, CBP-positive areas co-localized
      with both a halide peroxidase antibody and Lysotracker, a lysosomal marker,
      suggesting that the chitin-like biomolecule occurs in the lysosome or acidic
      vacuoles. Reverse transcriptase polymerase chain reaction (PCR) of hemocytes
      revealed mRNA coding for a chitin synthase, suggesting that the hemocytes
      synthesize chitin de novo. Finally, upon surveying blood cells from other
      invertebrate species, we observed CBP-positive regions in all granular blood
      cells examined, suggesting that this feature is a shared character among the
      invertebrates; the vertebrate blood cells that we sampled did not label with CBP.
      Although the function of the chitin-like material remains undetermined, its
      presence and subcellular location in invertebrate hemocytes suggests a conserved
      role for this polysaccharide in the immune system of diverse animals.

PMID- 21723108
TI  - Damping capacity is evolutionarily conserved in the radial silk of orb-weaving
      spiders.
AB  - Orb-weaving spiders depend upon their two-dimensional silk traps to stop insects
      in mid flight. While the silks used to construct orb webs must be extremely tough
      to absorb the tremendous kinetic energy of insect prey, webs must also minimize
      the return of that energy to prey to prevent insects from bouncing out of
      oscillating webs. We therefore predict that the damping capacity of major
      ampullate spider silk, which forms the supporting frames and radial threads of
      orb webs, should be evolutionarily conserved among orb-weaving spiders. We test
      this prediction by comparing silk from six diverse species of orb spiders. Silk
      was taken directly from the radii of orb webs and a Nano Bionix test system was
      used either to sequentially extend the silk to 25% strain in 5% increments while
      relaxing it fully between each cycle, or to pull virgin silk samples to 15%
      strain. Damping capacity was then calculated as the percent difference in loading
      and unloading energies. Damping capacity increased after yield for all species
      and typically ranged from 40 to 50% within each cycle for sequentially pulled
      silk and from 50 to 70% for virgin samples. Lower damping at smaller strains may
      allow orb webs to withstand minor perturbations from wind and small prey while
      still retaining the ability to capture large insects. The similarity in damping
      capacity of silk from the radii spun by diverse spiders highlights the importance
      of energy absorption by silk for orb-weaving spiders.

PMID- 21723109
TI  - Cervicofacial subcutaneous emphysema and pneumomediastinum after retinal
      detachment surgery: just another monitored anesthesia eye case.
AB  - Repair of a retinal detachment was performed during a retrobulbar block with
      monitored anesthesia care and intravenous conscious sedation. Following the
      procedure and after removal of the sterile drapes, the patient exhibited
      significant swelling of the bilateral orbits, face, neck, and chest. Subcutaneous
      emphysema and pneumomediastinum were confirmed on postoperative chest radiographs
      and computed tomographic scans. Possible mechanisms and potential sequelae of
      this intraoperative event are discussed.

PMID- 21723110
TI  - Quantitative analysis of mononucleotides by isotopic labeling surface-enhanced
      Raman scattering spectroscopy.
AB  - A novel surface-enhanced Raman scattering (SERS) approach for accurate
      quantification of mononucleotides of deoxyribonucleic acid (DNA) is described.
      Reproducible SERS measurement was achieved by using isotopically labeled internal
      standard. By measuring the SERS spectra of mononucleotides and its isotope
      internal standard in combination with multivariate data analysis, the method was
      successfully applied to quantify mononucleotides. The independent validation of
      analyte concentrations gave a standard deviation of within 2%, which is
      comparable to HPLC result. Finally, a mixture of four mononucleotides of DNA was
      prepared to explore the possibility of quantifying the concentration of label
      free, sequence-specific DNA strands by this approach. As compared to liquid
      chromatography/mass spectrometry (LC/MS), our method can be similarly precise but
      the SERS measurement is simple, rapid and potentially cheap.

PMID- 21723111
TI  - The effects of variations in the density and composition of eye materials on
      ophthalmic brachytherapy dosimetry.
AB  - In ophthalmic brachytherapy dosimetry, it is common to consider the water phantom
      as human eye anatomy. However, for better clinical analysis, there is a need for
      the dose determination in different parts of the eye. In this work, a full human
      eye is simulated with MCNP-4C code by considering all parts of the eye, i.e., the
      lens, cornea, retina, choroid, sclera, anterior chamber, optic nerve, and bulk of
      the eye comprising vitreous body and tumor. The average dose in different parts
      of this full model of the human eye is determined and the results are compared
      with the dose calculated in water phantom. The central axes depth dose and the
      dose in whole of the tumor for these 2 simulated eye models are calculated as
      well, and the results are compared.

PMID- 21723112
TI  - Determination of peripheral underdosage at the lung-tumor interface using Monte
      Carlo radiation transport calculations.
AB  - Prediction of dose distributions in close proximity to interfaces is difficult.
      In the context of radiotherapy of lung tumors, this may affect the minimum dose
      received by lesions and is particularly important when prescribing dose to
      covering isodoses. The objective of this work is to quantify underdosage in key
      regions around a hypothetical target using Monte Carlo dose calculation methods,
      and to develop a factor for clinical estimation of such underdosage. A systematic
      set of calculations are undertaken using 2 Monte Carlo radiation transport codes
      (egsnrc and geant4). Discrepancies in dose are determined for a number of
      parameters, including beam energy, tumor size, field size, and distance from
      chest wall. Calculations were performed for 1-mm3 regions at proximal, distal,
      and lateral aspects of a spherical tumor, determined for a 6-MV and a 15-MV
      photon beam. The simulations indicate regions of tumor underdose at the tumor
      lung interface. Results are presented as ratios of the dose at key peripheral
      regions to the dose at the center of the tumor, a point at which the treatment
      planning system (TPS) predicts the dose more reliably. Comparison with TPS data
      (pencil-beam convolution) indicates such underdosage would not have been
      predicted accurately in the clinic. We define a dose reduction factor (DRF) as
      the average of the dose in the periphery in the 6 cardinal directions divided by
      the central dose in the target, the mean of which is 0.97 and 0.95 for a 6-MV and
      15-MV beam, respectively. The DRF can assist clinicians in the estimation of the
      magnitude of potential discrepancies between prescribed and delivered dose
      distributions as a function of tumor size and location. Calculation for a
      systematic set of "generic" tumors allows application to many classes of patient
      case, and is particularly useful for interpreting clinical trial data.

PMID- 21723113
TI  - Trigeminal neuralgia treatment dosimetry of the Cyberknife.
AB  - There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is
      positioned on the patient's right, whereas the second is on the patient's left.
      The present study examines whether there is any difference in dosimetry when we
      are treating patients with trigeminal neuralgia when the target is on the right
      side or the left side of the patient. In addition, we also study whether Monte
      Carlo dose calculation has any effect on the dosimetry. We concluded that the
      clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia
      are independent of the robot position. Monte Carlo calculation algorithm may be
      useful in deriving the dose necessary for trigeminal neuralgia treatments.

PMID- 21723115
TI  - In-situ upgrading of biomass pyrolysis vapors: catalyst screening on a fixed bed
      reactor.
AB  - In-situ catalytic upgrading of biomass fast pyrolysis vapors was performed in a
      fixed bed bench-scale reactor at 500 degrees C, for catalyst screening purposes.
      The catalytic materials tested include a commercial equilibrium FCC catalyst (E
      cat), various commercial ZSM-5 formulations, magnesium oxide and alumina
      materials with varying specific surface areas, nickel monoxide, zirconia/titania,
      tetragonal zirconia, titania and silica alumina. The bio-oil was characterized
      measuring its water content, the carbon-hydrogen-oxygen (by difference) content
      and the chemical composition of its organic fraction. Each catalytic material
      displayed different catalytic effects. High surface area alumina catalysts
      displayed the highest selectivity towards hydrocarbons, yielding however low
      organic liquid products. Zirconia/titania exhibited good selectivity towards
      desired compounds, yielding higher organic liquid product than the alumina
      catalysts. The ZSM-5 formulation with the highest surface area displayed the most
      balanced performance having a moderate selectivity towards hydrocarbons, reducing
      undesirable compounds and producing organic liquid products at acceptable yields.

PMID- 21723114
TI  - Synchrony in sensation.
AB  - How neurons encode information has been a hotly debated issue. Ultimately, any
      code must be relevant to the senders, receivers, and connections between them.
      This review focuses on the transmission of sensory information through the
      circuit linking thalamus and cortex, two distant brain regions. Strong
      feedforward inhibition in the thalamocortical circuit renders cortex highly
      sensitive to the thalamic synchrony evoked by a sensory stimulus. Neuromodulators
      and feedback connections may modulate the temporal sensitivity of such circuits
      and gate the propagation of synchrony into other layers and cortical areas. The
      prevalence of strong feedforward inhibitory circuits throughout the central
      nervous system suggests that synchrony codes and timing-sensitive circuits may be
      widespread, occurring well beyond sensory thalamus and cortex.

PMID- 21723116
TI  - Purification and characterization of a novel cellobiohydrolase (PdCel6A) from
      Penicillium decumbens JU-A10 for bioethanol production.
AB  - An acidic Cel6A, cellobiohydrolase (CBH) II, was purified from Penicillium
      decumbens and designated as PdCel6A. The deduced internal amino acid sequence of
      the novel CBH has a high degree of sequence identity with the CBH II from
      Aspergillus fumigatus. Surprisingly, PdCel6A exhibits characteristics comparable
      to that of CBH I, as well as CBH II. Similar to CBH I, the novel CBH has a
      specific activity of 1.9 IU/mg against p-nitrophenyl-beta-d-cellobioside. The
      enzyme retains about 80% of its maximum activity after 4h of incubation at pH
      2.0. Using delignified corncob residue as the substrate, ethanol concentration
      increased by 20% during simultaneous saccharification and fermentation when
      supplemented with low doses of PdCel6A (0.2mg/g substrate). To our knowledge,
      this is the first report involving a CBH I-like CBH II. The present paper
      provides new insight into the role of CBH II in cellulose degradation.

PMID- 21723117
TI  - Rapid start-up of thermophilic anaerobic digestion with the turf fraction of MSW
      as inoculum.
AB  - This study aims to determine suitable start-up conditions and inoculum sources
      for thermophilic anaerobic digestion. Within days of incubation MSW at 55 degrees
      C, methane was produced at a high rate. In an attempt to narrow down which
      components of typical MSW contained the thermophilic methanogens, vacuum cleaner
      dust, banana peel, kitchen waste, and garden waste were tested as inoculum for
      thermophilic methanogenesis with acetate as the substrate. Results singled out
      grass turf as the key source of thermophilic acetate degrading methanogenic
      consortia. Within 4 days of anaerobic incubation (55 degrees C), anaerobically
      incubated grass turf samples produced methane accompanied by acetate degradation
      enabling successful start-up of thermophilic anaerobic digestion. Other essential
      start-up conditions are specified. Stirring of the culture was not conducive for
      successful start-up as it resulted specifically in propionate accumulation.

PMID- 21723118
TI  - Activated carbons from sisal waste by chemical activation with K2CO3: kinetics of
      paracetamol and ibuprofen removal from aqueous solution.
AB  - Sisal waste was used as precursor to prepare carbons by chemical activation. The
      influence of the K(2)CO(3) amount and activation temperature on the materials
      textural properties were studied through N(2) and CO(2) adsorption assays. As the
      severity of the treatment increases there is a development of supermicropores,
      and the micropore size distribution changes from mono to bimodal. A carbon with
      an apparent surface area of 1,038 m(2)g(-1) and pore volume of 0.49 cm(3)g(-1)
      was obtained. TPD results showed the incidence in acidic type groups although the
      pH(PZC) reveals an almost neutral character of the surface. Adsorption kinetic
      data of ibuprofen and paracetamol show that the processes obey to a pseudo-second
      order kinetic equation. Regarding the removal efficiency the prepared samples
      attained values comparable to a commercial carbon (>65%), revealing that chemical
      activation of sisal wastes with K(2)CO(3) allows obtaining samples suitable for
      pharmaceutical compounds removal from liquid phase.

PMID- 21723119
TI  - Synthesis and anti-inflammatory activity of novel biscoumarin-chalcone hybrids.
AB  - A series of synthesized novel biscoumarin-chalcone hybrids were evaluated for
      their anti-inflammatory and antioxidant activity. The tested compounds
      significantly inhibit the carrageenin induced paw oedema in albino rats and also
      exhibit important scavenging activities. These compounds thus constitute an
      interesting template for the design of new therapeutic tools against
      inflammation.

PMID- 21723120
TI  - Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as
      potent and selective MPS1 kinase inhibitors.
AB  - The synthesis and SAR of a series of novel pyrazolo-quinazolines as potent and
      selective MPS1 inhibitors are reported. We describe the optimization of the
      initial hit, identified by screening the internal library collection, into an
      orally available, potent and selective MPS1 inhibitor.

PMID- 21723121
TI  - Synthesis and biological activities of 4-N-(anilinyl-n-[oxazolyl])-7
      chloroquinolines (n=3' or 4') against Plasmodium falciparum in in vitro models.
AB  - The synthesis (Pd-mediated coupling strategy) and characterization (NMR, IR,
      elemental analysis, etc.) of a short series of quinoline-oxazole hybrid compounds
      has been carried out. These materials are found to be moderately active against
      Plasmodium falciparum in vitro, with activities in the sub-micromolar range, and
      to display acceptable cytotoxicity to mononuclear leukocytes. Chemical
      modification strategies, with the intention to increase the biological potency of
      this new class of anti-malarial agents, are discussed.

PMID- 21723122
TI  - Synthesis of aurones and their inhibitory effects on nitric oxide and PGE2
      productions in LPS-induced RAW 264.7 cells.
AB  - Sulfuretin is one of major constituents of Rhus verniciflua that exerts anti
      inflammatory activities. Some of aurones were synthesized as sulfuretin
      derivatives and evaluated for their abilities to inhibit NO and PGE(2) production
      in LPS-induced RAW 264.7 cells in order to reveal the relationship. Of the
      aurones synthesized in the present study, 2h and 2i, which possess C-6 hydroxyl
      group in A-ring and methoxy substituents in B-ring, more potently inhibited NO
      and PGE(2) production and were less cytotoxic than sulfuretin.

PMID- 21723123
TI  - N-beta-glycosyl sulfamides are selective inhibitors of the cancer associated
      carbonic anhydrase isoforms IX and XII.
AB  - The transmembrane isoforms of carbonic anhydrase (CA IX and XII) have been shown
      to be linked to carcinogenesis and their inhibition to arrest primary tumor and
      metastases growth. In this Letter, we present a series of peracetylated and
      deprotected N-beta-glycosyl sulfamides that were tested for the inhibition of 4
      carbonic anhydrase isoforms: the cytosolic hCA I and hCA II and transmembrane
      tumor-associated IX and XII. Compounds 1-4 and 6-8 selectively target cancer
      associated CAs (IX and XII) with K(I)s in the low nanomolar range.

PMID- 21723124
TI  - Scoliosis surgery in a patient with "de novo" myosin storage myopathy.
AB  - Myosin storage myopathy is a rare neuromuscular disorder, characterized by
      subsarcolemmal inclusions exclusively in type I skeletal muscle fibers, known as
      hyaline bodies. Its clinical spectrum is diverse, as are its modes of
      inheritance. Myosin storage myopathy, also called hyaline body myopathy, is
      caused by a pathogenic mutation in the MYH7 gene, encoding for the slow/beta
      cardiac myosin heavy chain. We describe a patient with this uncommon myopathy,
      caused by a new p.K1784delK mutation in the MYH7 gene. The patient developed a
      severe thoracolumbar scoliosis and had scoliosis surgery.

PMID- 21723125
TI  - A chimpanzee recognizes synthetic speech with significantly reduced acoustic cues
      to phonetic content.
AB  - A long-standing debate concerns whether humans are specialized for speech
      perception, which some researchers argue is demonstrated by the ability to
      understand synthetic speech with significantly reduced acoustic cues to phonetic
      content. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken
      words, asking whether she could understand such speech. Three experiments
      presented 48 individual words, with the animal selecting a corresponding
      visuographic symbol from among four alternatives. Experiment 1 tested spectrally
      reduced, noise-vocoded (NV) synthesis, originally developed to simulate input
      received by human cochlear-implant users. Experiment 2 tested "impossibly
      unspeechlike" sine-wave (SW) synthesis, which reduces speech to just three moving
      tones. Although receiving only intermittent and noncontingent reward, the
      chimpanzee performed well above chance level, including when hearing synthetic
      versions for the first time. Recognition of SW words was least accurate but
      improved in experiment 3 when natural words in the same session were rewarded.
      The chimpanzee was more accurate with NV than SW versions, as were 32 human
      participants hearing these items. The chimpanzee's ability to spontaneously
      recognize acoustically reduced synthetic words suggests that experience rather
      than specialization is critical for speech-perception capabilities that some have
      suggested are uniquely human.

PMID- 21723126
TI  - Structural organization of the actin cytoskeleton at sites of clathrin-mediated
      endocytosis.
AB  - BACKGROUND: The dynamic actin cytoskeleton plays an important role in clathrin
      mediated endocytosis (CME). However, its exact functions remain uncertain as a
      result of a lack of high-resolution structural information regarding actin
      architecture at endocytic sites. RESULTS: Using platinum replica electron
      microscopy in combination with electron tomography, we found that actin patches
      associated with clathrin-coated structures (CCSs) in cultured mouse cells consist
      of a densely branched actin network, in which actin filament barbed ends are
      oriented toward the CCS. The shape of the actin network varied from a small
      lateral patch at the periphery of shallow CCSs, to a collar-like arrangement
      around partly invaginated CCSs with actin filament barbed ends abutting the CCS
      neck, to a polarized comet tail in association with highly constricted or fully
      endocytosed CCSs. CONCLUSIONS: Our data suggest that the primary role of the
      actin cytoskeleton in CME is to constrict and elongate the bud neck and drive the
      endocytosed vesicles from the plasma membrane. Moreover, in these processes,
      barbed ends directly push onto the load, as in a conventional propulsion
      mechanism. Based on our findings, we propose a model for initiation, evolution,
      and function of the dendritic actin network at CCSs.

PMID- 21723127
TI  - Feedback control in sensing chromosome biorientation by the Aurora B kinase.
AB  - Maintenance of genome stability during cell division depends on establishing
      correct attachments between chromosomes and spindle microtubules. Correct,
      bioriented attachments are stabilized, whereas incorrect attachments are
      selectively destabilized. This process relies largely on increased
      phosphorylation of kinetochore substrates of Aurora B kinase at misaligned versus
      aligned kinetochores. Current models explain this differential phosphorylation by
      spatial changes in the position of substrates relative to a constant pool of
      kinase at the inner centromere. However, these models are based on studies in
      aneuploid cells. We show that normal diploid cells have a more robust error
      correction machinery. Aurora B is enriched at misaligned centromeres in these
      cells, and the dynamic range of Aurora B substrate phosphorylation at misaligned
      versus aligned kinetochores is increased. These findings indicate that in
      addition to Aurora B regulating kinetochore-microtubule binding, the kinetochore
      also controls Aurora B recruitment to the inner centromere. We show that this
      recruitment depends on both activity of Plk1, a kinetochore-localized kinase, and
      activity of Aurora B itself. Our results suggest a feedback mechanism in which
      Aurora B both regulates and is regulated by chromosome attachment to the spindle,
      which amplifies the differential phosphorylation of kinetochore substrates and
      increases the efficiency of error correction.

PMID- 21723128
TI  - Plk1 controls the Nek2A-PP1gamma antagonism in centrosome disjunction.
AB  - In human cells, separation of the centrosomes and formation of a bipolar spindle
      are essential for correct chromosome segregation [1]. During interphase,
      centrosomes are joined together by the linker proteins C-Nap1 and rootletin [2
      4]. At the onset of mitosis, these linker proteins are phosphorylated and
      displaced from centrosomes by the Nek2A kinase, which is regulated by two Hippo
      pathway components, Mst2 kinase and the scaffold protein hSav1. The kinesin-5
      motor protein Eg5 promotes centrosome separation in a parallel pathway to Nek2A
      [5]. Here, we report that Polo-like kinase 1 (Plk1) functions upstream of the
      Mst2-Nek2A kinase module in centrosome disjunction as well as being important for
      Eg5 localization at centrosomes. Plk1 regulates Mst2-Nek2A-induced centrosome
      disjunction by phosphorylating Mst2. The absence of Plk1 phosphorylation of Mst2
      promotes assembly of Nek2A-PP1gamma-Mst2 complexes, in which PP1gamma counteracts
      Nek2A kinase activity. In contrast, Plk1 phosphorylation of Mst2 prevents
      PP1gamma binding to Mst2-Nek2A, allowing Nek2A activity to promote centrosome
      disjunction. We propose that centrosome disjunction is regulated by Plk1,
      providing a well-balanced control between the counteracting Nek2A and PP1gamma
      activities on the centrosome linker.

PMID- 21723129
TI  - Rhythmic TMS causes local entrainment of natural oscillatory signatures.
AB  - BACKGROUND: Neuronal elements underlying perception, cognition, and action
      exhibit distinct oscillatory phenomena, measured in humans by electro- or
      magnetoencephalography (EEG/MEG). So far, the correlative or causal nature of the
      link between brain oscillations and functions has remained elusive. A compelling
      demonstration of causality would primarily generate oscillatory signatures that
      are known to correlate with particular cognitive functions and then assess the
      behavioral consequences. Here, we provide the first direct evidence for causal
      entrainment of brain oscillations by transcranial magnetic stimulation (TMS)
      using concurrent EEG. RESULTS: We used rhythmic TMS bursts to directly interact
      with an MEG-identified parietal alpha-oscillator, activated by attention and
      linked to perception. With TMS bursts tuned to its preferred alpha-frequency
      (alpha-TMS), we confirmed the three main predictions of entrainment of a natural
      oscillator: (1) that alpha-oscillations are induced during alpha-TMS (reproducing
      an oscillatory signature of the stimulated parietal cortex), (2) that there is
      progressive enhancement of this alpha-activity (synchronizing the targeted, alpha
      generator to the alpha-TMS train), and (3) that this depends on the pre-TMS phase
      of the background alpha-rhythm (entrainment of natural, ongoing alpha
      oscillations). Control conditions testing different TMS burst profiles and TMS
      EEG in a phantom head confirmed specificity of alpha-boosting to the case of
      synchronization between TMS train and neural oscillator. CONCLUSIONS: The
      periodic electromagnetic force that is generated during rhythmic TMS can cause
      local entrainment of natural brain oscillations, emulating oscillatory signatures
      activated by cognitive tasks. This reveals a new mechanism of online TMS action
      on brain activity and can account for frequency-specific behavioral TMS effects
      at the level of biologically relevant rhythms.

PMID- 21723130
TI  - Early specialization for voice and emotion processing in the infant brain.
AB  - Human voices play a fundamental role in social communication, and areas of the
      adult "social brain" show specialization for processing voices and their
      emotional content (superior temporal sulcus, inferior prefrontal cortex, premotor
      cortical regions, amygdala, and insula). However, it is unclear when this
      specialization develops. Functional magnetic resonance (fMRI) studies suggest
      that the infant temporal cortex does not differentiate speech from music or
      backward speech, but a prior study with functional near-infrared spectroscopy
      revealed preferential activation for human voices in 7-month-olds, in a more
      posterior location of the temporal cortex than in adults. However, the brain
      networks involved in processing nonspeech human vocalizations in early
      development are still unknown. To address this issue, in the present fMRI study,
      3- to 7-month-olds were presented with adult nonspeech vocalizations (emotionally
      neutral, emotionally positive, and emotionally negative) and nonvocal
      environmental sounds. Infants displayed significant differential activation in
      the anterior portion of the temporal cortex, similarly to adults. Moreover, sad
      vocalizations modulated the activity of brain regions involved in processing
      affective stimuli such as the orbitofrontal cortex and insula. These results
      suggest remarkably early functional specialization for processing human voice and
      negative emotions.

PMID- 21723131
TI  - Influence of gait analysis on decision-making for lower extremity orthopaedic
      surgery: Baseline data from a randomized controlled trial.
AB  - Previous studies examining the influence of gait analysis on surgical decision
      making have been limited by the lack of a control group. The aim of this study
      was to use data from a randomized controlled trial to determine the effects of
      gait analysis on surgical decision-making in children with cerebral palsy (CP).
      178 ambulatory children with CP (110 male; age 10.3+/-3.8 years) being considered
      for lower extremity orthopaedic surgery underwent gait analysis and were
      randomized into one of two groups: gait report group (N=90), where the
      orthopaedic surgeon received the gait analysis report, and control group (N=88),
      where the surgeon did not receive the gait report. Data regarding specific
      surgeries were recorded by the treating surgeon before gait analysis, by the gait
      laboratory surgeon after gait analysis, and after surgery. Agreement between the
      treatment done and the gait analysis recommendations was compared between groups
      using the 2-sided Fisher's Exact test. When a procedure was planned initially and
      also recommended by gait analysis, it was performed more often in the gait report
      group (91% vs. 70%, p<0.001). When the gait laboratory recommended against a
      planned procedure, the plan was changed more frequently in the gait report group
      (48% vs. 27%, p=0.009). When the gait laboratory recommended adding a procedure,
      it was added more frequently in the gait report group (12% vs. 7%, p=0.037).
      These results provide a stronger level of evidence demonstrating that gait
      analysis changes treatment decision-making and also reinforces decision-making
      when it agrees with the surgeon's original plan.

PMID- 21723132
TI  - Classification of the reduced vertical component of the ground reaction force in
      late stance in cerebral palsy gait.
AB  - Children with cerebral palsy (CP) often experience significant problems
      supporting their bodyweight (BW) and decelerating the downward velocity of the
      centre of mass (CoM) in late stance. This is seen as a decreased second peak of
      vertical ground reaction force (GRF) nominated FZ(2). This study categorises gait
      data by the degree of reduced FZ(2). Kinetic data were analysed from a CP
      database. Data from 129 patients, able to walk barefoot unaided, were
      investigated. Of these, 84 had kinetic data, 59 diplegics (both legs) and 15
      hemiplegics (affected leg only), thus providing data from 133 legs. A reduced
      FZ(2) was observed in 116 legs (87%). Of the 133 legs, 44% failed to generate
      FZ(2)>BW. By including the Type 2 data this figure rises to, a staggering 66% who
      are having difficulty supporting BW at this stage of the stance phase. Only 12%
      of the legs showed a normal pattern (FZ(2) approximately equal to FZ(1)). In
      conclusion, the majority of CP children referred to the gait laboratory exhibited
      some degree of reduced FZ(2) and can be categorised as having a 'Ben Lomonding'
      gait pattern. 'Ben Lomonding,' is the term used to describe this phenomenon of
      reduced FZ(2), as the shape of the GRF graph resembles the shape of the Scottish
      mountain, Ben Lomond, which has two peaks, the second peak being much smaller
      than the first. Crucially, clinicians should be aware that nearly half of the CP
      children in this study were in difficulty supporting their BW in late stance and
      must use compensatory mechanisms to prevent collapse of the affected limb.

PMID- 21723133
TI  - Measuring brain temperature while maintaining brain normothermia in patients with
      severe traumatic brain injury.
AB  - The aim of this study was to evaluate the relationship between superficial
      temporal artery temperature (Tt), rectal temperature (Tr) and intracranial
      temperature (ICT) when attempting to keep the brain in a normothermic condition
      in patients with severe traumatic brain injury (TBI). We also compared the
      incidence of temperature gradient reversal in patients who survived (survivors)
      and patients who did not (non-survivors) and the difference in temperature
      gradient reversal between survivors and non-survivors. Tr is normally lower than
      and ICT and temperature gradient reversal, when Tr exceeds ICT, has been
      demonstrated to be an early sign of brain death. A total of 28 patients with
      severe TBI were enrolled retrospectively in our study between November 2008 and
      February 2010. Each patient's Tt, Tr and ICT was recorded every hour for 4 days.
      Our results show that the frequency of brain hyperthermia in our participants
      (ICT>38 degrees C) was 17.7%. Using a paired t-test and Bland-Altman plots, it
      was shown that a significant temperature difference existed between Tt, Tr and
      ICT (p<0.001). The use of Spearman's correlation method revealed that Tt, Tr and
      ICT were positively correlated (p<0.001). Brain death occurred in five patients
      at a mean of 9.6 hours (range: 8-12 hours) after a temperature gradient reversal
      between Tt, Tr and ICT. Fisher's exact test showed that there was a significant
      difference in the incidence of temperature gradient reversal between Tt, Tr and
      ICT in survivors and non-survivors (p<0.001). We conclude that a significant
      temperature difference exists between Tt, Tr and ICT when maintaining brain
      normothermia. The daily practice of non-invasive Tt measurement may cause doctors
      to underestimate ICT; reversal of the ICT and Tt and/or Tr temperatures could be
      an early marker of a poor prognosis for patients with severe TBI.

PMID- 21723134
TI  - Performance of optically stimulated luminescence Al2O3 dosimeter for low doses of
      diagnostic energy X-rays.
AB  - Personal dosimeters measure the radiation dose from exposure to hazardous sources
      outside the body. The present manuscript evaluates the performance of a
      commercially available optically stimulated luminescence (OSL) Al2O3 dosimeter
      using diagnostic energy X-rays. The OSL system satisfies the ANSI N13.11-2001
      performance criteria for low dose diagnostic energy X-rays. Non-uniformity of
      sensitivity, dose linearity, X-ray energy response, and angular performance are
      all within the criteria of IEC-62387-1(2007).

PMID- 21723135
TI  - Production of glass microspheres comprising 90Y and (177)Lu for treating of
      hepatic tumors with SPECT imaging capabilities.
AB  - Our objective was to determine if glass microspheres impregnated with two
      radionuclides, (90)Y as source of therapeutic beta emissions and (177)Lu as
      source of diagnostic gamma emissions can be useful for SPECT imaging during or
      after application of the (90)Y microspheres for treating of hepatic tumors. The
      glass-based microspheres labeled with (89)Y and lutetium (YAS (Lu)) or (89)Y and
      ytterbium (YAS (Yb)) were prepared by the sol-gel process where sol droplets
      directly were formed to gel microspheres. Results of the neutron activation
      indicate that such a combination of glass, microspheres allow bio-distribution
      studies by SPECT imaging with high resolution.

PMID- 21723136
TI  - An analytical approach to gamma-ray self-shielding effects for radioactive bodies
      encountered nuclear decommissioning scenarios.
AB  - A novel analytical approach is described that accounts for self-shielding of
      gamma radiation in decommissioning scenarios. The approach is developed with
      plutonium-239, cobalt-60 and caesium-137 as examples; stainless steel and
      concrete have been chosen as the media for cobalt-60 and caesium-137,
      respectively. The analytical methods have been compared MCNPX 2.6.0 simulations.
      A simple, linear correction factor relates the analytical results and the
      simulated estimates. This has the potential to greatly simplify the estimation of
      self-shielding effects in decommissioning activities.

PMID- 21723137
TI  - Evaluation of excitation functions of proton, 3He- and alpha-particle induced
      reactions for production of the medically interesting positron-emitter bromine
      76.
AB  - Cross section data for production of the medically interesting radionuclide 76Br
      (T(1/2)=16.2 h) via the proton induced reactions on 76Se, 77Se, 78Se and 79Br,
      and 3He- and alpha-particle induced reactions on 75As were evaluated. The nuclear
      model codes STAPRE, EMPIRE and TALYS were used to check the consistency in the
      experimental data and a statistical procedure was applied to derive the
      recommended excitation functions. A comparison of various production routes of
      76Br (and of 75Br) is presented.

PMID- 21723138
TI  - Study on bubble detectors used as personal neutron dosimeters.
AB  - Neutron bubble detector is so far the only personal neutron dosimeter satisfying
      the energy response criteria of the International Committee of Radiation
      Protection 60 (ICRP 60). This paper presents our studies on neutron bubble
      detectors including the manufacture, the relevant equipments, the basic
      calibrations and on-site tests for monitoring personal neutron dose. The results
      of calibrations show that the highest sensitivity so far manufactured by the
      authors reaches about 4bubbles/MUSv, the correlation coefficient of dose response
      is 0.99, and the in-batch consistency and reproducibility are up to the ISO
      standards. The results of on-site test show that the in-batch consistency and
      between-batch consistency are within 15% relative standard uncertainty. The
      results are directly readable. The detectors are portable, especially suitable
      for on-site neutron dose monitoring in n-gamma mixed radiation fields.

PMID- 21723139
TI  - Assessment of Atmospheric heavy metal deposition in North Egypt aerosols using
      neutron activation analysis and optical emission inductively coupled plasma.
AB  - The aim of the present study is to assess the current level of atmospheric heavy
      metal pollution of aerosols in different cities of North Egypt using the neutron
      activation analysis and optical emission inductively coupled plasma techniques.
      The results revealed that the highest concentrations of particulate matter PM10
      and total suspended particulate matter were close to industrial areas. From the
      results of the enrichment factor calculations, the most significant elements of
      anthropogenic origin are Ba, Sb, Ce and Zn.

PMID- 21723140
TI  - Liquid chromatography/time-of-flight mass spectrometry for the analysis of plant
      samples: a method for simultaneous screening of common cofactors or nucleotides
      and application to an engineered plant line.
AB  - Intense efforts are currently devoted to improve plant metabolomic analyses so as
      to describe more accurately the whole picture of metabolic pathways. Analyses
      based on liquid chromatography/time-of-flight mass spectrometry (LC-TOF) are now
      widely distributed among plant science laboratories. However, the use of
      reliable, sensitive LC-TOF methods to identify and quantify micromolar or
      inframicromolar key metabolites is often impeded by the sensitivity of the
      technique to sample preparation or chromatographic conditions. Typically, the
      sample matrix has a substantial influence on ionization efficiency and therefore,
      on the detectability of such compounds. Here, we describe a new method to analyze
      simultaneously 23 nucleotides and cofactors from plant extracts, taking advantage
      of solid-phase extraction (SPE) prior to injection. The influence of common m/z
      fragments in several metabolites and adducts is considered. We applied this
      method to characterise metabolic intermediates of NAD biosynthesis in Arabidopsis
      thaliana, using a wild-type and an engineered transgenic plant line that produces
      bacterial quinolinate phosphoribosyl transferase (nadc). We show that sample pre
      purification with SPE is strictly required not only for compound quantification
      and identification but also to allow ionization of matrix-sensitive compounds
      (e.g. nicotinamide) or alleviate fragmentation of others (e.g. NAD). When
      exogenous substrate quinolinate was infiltrated into Arabidopsis leaves to
      increase the natural content in downstream metabolites, a clear correlation
      between intermediates of NAD biosynthesis was seen, showing the accuracy of our
      method for quantification in biological samples. Nadc plants only showed very
      modest changes in NAD-related metabolites and furthermore, they were associated
      with slightly lower photosynthetic performance and ATP production.

PMID- 21723141
TI  - Guided bone regeneration in pig calvarial bone defects using autologous
      mesenchymal stem/progenitor cells - a comparison of different tissue sources.
AB  - Due to donor side morbidity and the absence of osteogenic properties in bone
      substitutes, there is a growing need for an alternative to traditional bone
      grafting within the scope of tissue engineering. This animal study was conducted
      to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum
      derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells
      (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were
      induced into osteogenic differentiation following in vitro cell expansion. Ex
      vivo cultivated cells were seeded on a collagen scaffold and subsequently added
      to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure
      collagen scaffold served as a control defect. The animals were sacrificed at
      specific time points and de novo bone formation was quantitatively analyzed by
      histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization
      rate of newly formed bone were compared among the groups. In the early stages of
      wound healing, up to 30 days, the test defects did not show better bone
      regeneration than those in the control defect, but the bone healing process in
      the test defects was accelerated in the later stage compared to those in the
      control defect. All the test defects showed complete osseous healing after 90
      days compared to those in the control defect. During the observation period, no
      significant differences in BV/TV and mineralization of newly formed bone among
      the test defects were observed. Irrespective of the tissue sources of MSC, the
      speed and pattern of osseous healing after cell transplantations into
      monocortical bone defects were comparable. Our results indicate that the
      efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex
      vivo cell expansion is not significantly different for the guided regeneration of
      bone defects.

PMID- 21723142
TI  - The use of photosensitisers in acne treatment.
AB  - Whereas the standard approach to the treatment of acne vulgaris has involved both
      systemic and topical antibiotics and topical agents such as benzoyl peroxide,
      problems exist due to side effects, drug resistance and lack of compliance. The
      photoantimicrobial approach offers a rapid treatment for large areas of afflicted
      dermis, based on the generation of reactive oxygen species in situ. Various
      chemical types are available as a topical modality, both in respect of the
      photosensitising agent and the activating light source, the suggested therapeutic
      approach requiring medical supervision. Due to a novel mode of action, the use of
      photosensitisers constitutes a convenient option against drug-resistant bacteria.

PMID- 21723143
TI  - Assessing physical function and activity for survivors of a critical illness: a
      review of instruments.
AB  - BACKGROUND: Functional outcomes and health-related quality of life are important
      measures for survivors of a critical illness. Studies have demonstrated
      debilitating physical effects for a significant proportion of surviving patients,
      particularly those with intensive care unit-acquired weakness. Contemporary
      practice changes include a focus on the continuum of critical illness, with less
      sedation and more physical activity including mobility while in ICU, and post-ICU
      and post-hospitalisation activities to support optimal recovery. How to best
      assess the physical function of patients at different phases of their recovery
      and rehabilitation is therefore important. PURPOSE: This narrative review paper
      examined observational and functional assessment instruments used for assessing
      patients across the in-ICU, post-ICU and post-hospital continuum of critical
      illness. METHODS: Relevant papers were identified from a search of bibliographic
      databases and a review of the reference list of selected articles. The
      clinimetric properties of physical function and HRQOL measures and their
      relevance and utility in ICU were reported in narrative format. FINDINGS: The
      review highlighted many different instruments used to measure function in
      survivors of ICU including muscle strength testing, functional tests and walk
      tests, and patient centred outcomes such as health related quality of life. In
      general, the sensitivity and validity of these instruments for use with survivors
      of a critical illness has not yet been established. CONCLUSION: Based on findings
      from the review, screening of patients using reliable and valid instruments for
      ICU patients is recommended to inform both practice and future studies of
      interventions aimed at improving recovery and rehabilitation.

PMID- 21723144
TI  - Genetic variation in BDNF is associated with allergic asthma and allergic
      rhinitis in an ethnic Chinese population in Singapore.
AB  - Allergic diseases affect more than 25% of the world population and result from a
      complex interplay between genetic and environmental factors. Recent evidence has
      shown that BDNF (Brain Derived Neurotrophic Factor) could serve as an important
      marker of allergic disease. Increased levels of BDNF in blood, bronchoalveolar
      lavage fluid and nasal lavage fluid positively correlate with disease activity
      and severity in patients with allergic rhinitis (AR), asthma and atopic eczema.
      However, reports on the association between genetic variation in BDNF and
      allergic disease have been controversial. This study therefore aims to clarify
      the relationship between single nucleotide polymorphisms (SNPs) in BDNF and a
      genetic predisposition to AR and asthma in an ethnic Chinese population of
      Singapore. Volunteers with a self-reported history of asthma (718 subjects) or a
      history of AR as determined by a researcher-administered questionnaire (795
      subjects) were used in this study, alongside controls with no personal or family
      history of allergy (717 subjects). The association results identified a
      significant association for the tagSNP rs10767664 with a significant
      PDominant=0.0007 and OR=1.3 for AR and PDominant=0.0005 and OR=1.3 for asthma
      (using a dominant model of association). The haplotype based analysis also
      identified a significant association further confirming the single SNP
      association. The SNP rs10767664 is strongly linked (r2=0.95) to the functional
      polymorphism rs6265 (Val66Met), which has previously been reported to be
      associated to allergic phenotypes and also shown to affect BDNF expression. BDNF
      is a therefore a key molecular player in allergy. Further studies on
      polymorphisms within BDNF may shed light on its role in the pathogenesis of
      allergic diseases and potentially serve as biomarkers for allergic disease.

PMID- 21723145
TI  - Low-frequency jet ventilation through a bronchial blocker for tracheal repair
      after a rare complication of percutaneous dilatational tracheostomy.

PMID- 21723146
TI  - Driving with a driveline: a survey of current practice patterns for allowing a
      patient supported with a left ventricular assist device to drive.

PMID- 21723147
TI  - My face through the looking-glass: the effect of mirror reversal on reflection
      size estimation.
AB  - People tend to grossly overestimate the size of their mirror-reflected face.
      Although this overestimation bias is robust, not much is known about its
      relationships to self-face perception. In two experiments, we investigated the
      overestimation bias as a function of the presentation of the own face (left-right
      reversed - as in a mirror - or nonreversed - as in a photograph), the identity of
      the seen face, and prior exposure to a real mirror. For this we developed a
      computerized task requiring size estimations of displayed faces. We replicated
      the observation that people overestimate the size of their mirror-reflected face
      and showed that the overestimation can be reduced following a brief mirror
      exposure. We also found that left-right reversal modulates the overestimation
      bias, depending on the perceived face's identity. These data underline the
      enhanced familiarity of left-right reversed self-faces and the importance of size
      perception for understanding mirror reflection processing.

PMID- 21723148
TI  - Pectoralis major tendon transfer for the treatment of scapular winging due to
      long thoracic nerve palsy.
AB  - BACKGROUND: Painful scapular winging due to chronic long thoracic nerve (LTN)
      palsy is a relatively rare disorder that can be difficult to treat. Pectoralis
      major tendon (PMT) transfer has been shown to be effective in relieving pain,
      improving cosmesis, and restoring function. However, the available body of
      literature consists of few, small-cohort studies, and more outcomes data are
      needed. MATERIALS AND METHODS: Outcomes of 26 consecutive patients with
      electromyelogram-confirmed LTN palsy who underwent direct (n = 4) or indirect
      transfer (n = 22) of the PMT for dynamic stabilization of the scapula were
      reviewed. All patients were followed up clinically for an average of 21.8 months
      (range, 3-62 months) with evaluations of active forward flexion, active external
      rotation, American Shoulder and Elbow Surgeons (ASES) score, visual analog scale
      (VAS) pain score, and observation of scapular winging. RESULTS: Preoperative to
      postoperative results included increases in the mean active forward flexion from
      112 degrees  to 149 degrees  (P < .001) an in mean active external rotation from
      53.8 degrees  to 62.8 degrees  (P = .045), an improvement in the mean ASES score
      from 28 to 67.0 (P < .001), and an improvement in the mean VAS pain score from
      7.7 to 3.0 (P < .001). Recurrent scapular winging occurred in 5 patients. There
      was no difference in outcome by length of follow-up. CONCLUSIONS: PMT transfer is
      an effective treatment for painful scapular winging resulting from LTN palsy.
      This is the largest reported series of consecutive patients treated with PMT
      transfer for the correction of scapular winging.

PMID- 21723149
TI  - Midshaft clavicular fractures: comparison of intramedullary pin and plate
      fixation.
AB  - BACKGROUND: Intramedullary pin and plate fixation for midshaft clavicular
      fractures both have their proponents, but little comparative data are available.
      We performed a retrospective comparison of these 2 techniques. MATERIALS AND
      METHODS: A retrospective review was performed on 40 consecutive patients with
      closed, simple, or wedge-type midshaft clavicular fractures that were identified
      from a prospectively collected orthopedic trauma database. Eight patients were
      excluded due to incomplete follow-up. Intramedullary pins were used in 18
      patients and plates in 14; of these, 7 plates were placed superiorly, 6
      anteriorly, and 1 inferiorly. Treatment method was determined by preference of
      the treating surgeon. RESULTS: Among the patients treated with intramedullary pin
      fixation, all 18 fractures healed, and each underwent a planned procedure for pin
      removal. Complications included 1 intraoperative pin breakage, 1 superficial
      wound infection, 2 prominent symptomatic pins, and 1 transient brachial
      plexopathy. Among the patients treated with plating, delayed union occurred in 1,
      and refractures occurred in 2 (1 required a second procedure). Three patients
      underwent plate removal for symptomatic hardware. No patients in either group had
      significant loss of shoulder motion. CONCLUSION: Intramedullary pin fixation for
      acute, simple, or wedge-type midshaft clavicular fractures provides a safe and
      predictable alternative to plate and screw fixation.

PMID- 21723150
TI  - Implantation of a porcine acellular dermal graft in a primate model of rotator
      cuff repair.
AB  - BACKGROUND: Non-cross-linked xenogeneic extracellular matrix graft materials have
      typically elicited a hypersensitivity reaction when implanted into humans or
      other primates. The purpose of this study was to examine the histologic and
      immune response to a non-cross-linked porcine-derived dermal extracellular matrix
      graft processed to remove the alpha-gal epitope. MATERIALS AND METHODS: Eight
      African green monkeys were implanted with porcine acellular dermal matrix (Conexa
      Reconstructive Tissue Matrix; Tornier Inc, Edina, MN, USA) to repair and augment
      a partial excision defect of the supraspinatus tendon of the rotator cuff. Four
      animals each were sacrificed at 3 months and 6 months, and histologic samples
      were compared with tissues harvested from unoperated shoulders. RESULTS: Gross
      examination of grafted Conexa showed the appearance of integration proximally
      with tendon and distally with bone in each operated rotator cuff complex.
      Histologically, Conexa appeared to have remodeled to tendon-like architecture,
      with homogeneous distribution of fibroblast cells and parallel alignment of
      collagen fibers, with the direction of force evident by 3 months after
      implantation. Abundant vasculature observed at 3 months, which diminished to
      native tendon levels by 6 months, also indicated this to be a period of
      significant remodeling with an absence of significant inflammation, as evidenced
      by immunochemical methods and serum analysis. CONCLUSION: Conexa porcine
      acellular dermal matrix allows for incorporation of host tendon tissue without a
      hypersensitivity reaction in a primate model and should be a safe material for
      augmentation of human rotator cuff repair.

PMID- 21723151
TI  - Risk factors for 30-day postoperative complications and mortality after below
      knee amputation: a study of 2,911 patients from the national surgical quality
      improvement program.
AB  - BACKGROUND: This investigation sought to evaluate risk factors for morbidity and
      mortality from a large series of below-knee amputees prospectively entered in a
      national database. STUDY DESIGN: All patients undergoing below-knee amputations
      in the years 2005-2008 were identified in the database of the National Surgical
      Quality Improvement Program (NSQIP). Demographic data, medical comorbidities, and
      medical history were obtained. Mortality and postoperative complications within
      30 days of the below-knee amputation were also documented. Chi-square test,
      univariate, and multivariate logistic regression analyses were used to assess the
      effect of specific risk factors on mortality, as well as the likelihood of
      developing major, minor, or any complications developing. RESULTS: Below-knee
      amputations were performed in 2,911 patients registered in the NSQIP database
      between 2005 and 2008. The average age of patients was 65.8 years old and 64.3%
      were male. There was a 7.0% 30-day mortality rate and 1,627 complications
      occurred in 1,013 patients (34.4%). Multivariate logistic regression analysis
      identified renal insufficiency, cardiac issues, history of sepsis, steroid use,
      COPD, and increased patient age as independent predictors of mortality. The most
      common major complications were return to the operating room (15.6%), wound
      infection (9.3%), and postoperative sepsis (9.3%). History of sepsis, alcohol
      use, steroid use, cardiac issues, renal insufficiency, and contaminated/infected
      wounds were independent predictors of one or more complications developing.
      CONCLUSIONS: Renal disease, cardiac issues, history of sepsis, steroid use, COPD,
      and increased patient age were identified as predictors of mortality after below
      knee amputation. Renal disease, cardiac issues, history of sepsis, steroid use,
      contaminated/infected wounds, and alcohol use were also found to be predictors of
      postoperative complications.

PMID- 21723152
TI  - Outcomes in geriatric genitourinary trauma.
AB  - BACKGROUND: Geriatric trauma patients (GTPs) are the fastest growing segment of
      patients admitted to trauma centers. We examined the characteristics and outcomes
      of genitourinary (GU) trauma sustained by GTPs compared with nongeriatric trauma
      patients (NGTPs). STUDY DESIGN: The National Trauma Data Bank v8.0 was searched
      by ICD-9 CM codes for GU injuries in GTPs 65 years or older compared with NGTPs
      aged 18 to 64 years. The incidence of GU trauma, mechanism of injury, Injury
      Severity Score (ISS), surgical intervention, pre-existing comorbidities, hospital
      complications, discharge disposition, and mortality were analyzed. Chi-square
      test was used to compare the distribution for categorical variables and t-test
      was used to compare means of continuous variables between GTPs and NGTPs.
      RESULTS: Of the 9,470 patients with GU trauma, 852 patients (9.0%) were 65 years
      old or older, and 8,618 patients (91.0%) were 18 to 64 years. GTPs were more
      likely to sustain injury to the bladder or urethra (28.9% vs 20.5% p < 0.001),
      and less likely to the penis (0.5% vs 3.4% p < 0.001) and scrotum or testes (1.5%
      vs 7.7% p < 0.001). Rates of injury to the kidney (67.5% vs 65.9%) were similar.
      GTPs more commonly sustained blunt trauma (92.8% vs 74.4% p < 0.0001). Although
      the mean Injury Severity Scores for GTPs and NGTPs were similar (17.7 vs 18.1),
      GTPs were more commonly admitted to the ICU (41.8% vs 31.6% p < 0.001) and had a
      longer ICU stay (6.6 vs 5.7 days p = 0.02). Renal embolization, nephrectomy, and
      nonoperative management of renal injuries were similar in both cohorts. GTPs had
      significantly more comorbidities and hospital complications. The mortality rate
      was significantly higher for GTPs (18.5% vs 9.9%, p < 0.0001). CONCLUSIONS: GTPs
      sustain a significant number of GU injuries. Penetrating GU injuries are less
      common in GTPs. Although GTPs and NGTPs had similar mean Injury Severity Scores,
      GTPs had more ICU admissions, longer ICU stays, and twice the mortality rate when
      compared with NGTPs.

PMID- 21723153
TI  - Current treatment for the local control of retroperitoneal sarcomas.

PMID- 21723154
TI  - Can biochemical abnormalities predict symptomatology in patients with primary
      hyperparathyroidism?
AB  - BACKGROUND: Primary hyperparathyroidism presents with a myriad of symptoms, which
      range in severity. The cause of these symptoms is not well understood. We sought
      to determine if the severity of preoperative biochemical abnormalities (calcium,
      parathyroid hormone, vitamin D levels) correlated with symptomatology in patients
      undergoing surgical treatment for primary hyperparathyroidism. STUDY DESIGN: Over
      15 months, 229 consecutive patients with primary hyperparathyroidism completed a
      symptom questionnaire before parathyroidectomy. The symptom profiles of patients
      with significant hypercalcemia at initial presentation (>=11.2 mg/dL) and those
      with baseline calcium levels (<11.2 mg/dL) were compared. The patients were also
      categorized based on parathyroid hormone (< or >=130 pg/mL) and vitamin D (< or
      >=30 ng/mL) and analyzed in a similar manner. RESULTS: Seventy-eight patients
      (34%) had a baseline calcium >=11.2 mg/dL, but compared with patients with
      calcium <11.2 mg/dL, only the incidence of nephrolithiasis was more common in
      those patients with significant hypercalcemia (18% vs 9%, p = 0.04). Conversely,
      depression, bone or joint pain, and constipation were all significantly more
      common in patients with calcium <11.2mg/dL (p = 0.006, 0.001, and 0.031,
      respectively). Patients analyzed based on parathyroid hormone and vitamin D
      levels showed no significant difference in symptom presentation. CONCLUSIONS:
      These data indicate that the degree of parathyroid hormone elevation and the
      presence of vitamin D deficiency do not correlate with the presence of symptoms
      in patients with primary hyperparathyroidism. Significant hypercalcemia was
      associated with nephrolithiasis, but interestingly, patients with milder
      hypercalcemia had significantly more depression, bone or joint pain, and
      constipation, suggesting that these symptoms are likely not mediated by
      hypercalcemia.

PMID- 21723155
TI  - Disparities in treatment and survival of white and Native American patients with
      colorectal cancer: a SEER analysis.
AB  - BACKGROUND: Minority groups with colorectal cancer have not experienced the
      decline in incidence and mortality that has been reported in whites. We sought to
      determine whether differences exist in treatment and survival between white and
      Native American patients with colorectal cancer because little has been written
      about this specific minority group. STUDY DESIGN: The Surveillance Epidemiology
      and End Results (SEER) database for colorectal cancer was used to compare
      treatment and survival in whites (colon, n = 137,949; rectum, n = 46,843) and
      Native Americans (colon, n = 872; rectum, n = 316). Cox proportional hazards
      models were used to compare cancer-specific survival in Native Americans with
      whites, adjusted for stage, sex, age and year of diagnosis, socioeconomic status,
      and treatment. RESULTS: Native Americans presented at younger ages than whites
      for both colon and rectal cancer (p < 0.001). They were diagnosed at more
      advanced stages of disease than whites for only colon cancer. No significant
      differences were detected in the proportion of patients recommended for surgery
      between the two groups, for either cancer at any stage (all p > 0.05). Native
      Americans with rectal cancer were more likely to receive radiation than whites (p
      < 0.001), but they received less sphincter-preserving surgery (60.0% vs 65.4%; p
      = 0.045). Native Americans with colon cancer fared significantly worse than
      whites (hazard ratio = 1.20; 95% CI = 1.08 to 1.34), but there is no difference
      in cancer-free survival between races for rectal cancer. CONCLUSIONS: Compared
      with whites, Native Americans with colon cancer have worse cancer-specific
      survival.

PMID- 21723156
TI  - The ubiquitin-editing protein A20 prevents dendritic cell activation, recognition
      of apoptotic cells, and systemic autoimmunity.
AB  - Dendritic cells (DCs) regulate both immunity and tolerance. Here we have shown
      that the ubiquitin editing enzyme A20 (Tnfaip3) determines the activation
      threshold of DCs, via control of canonical NF-kappaB activation.
      Tnfaip3(fl/fl)Cd11c-cre(+) mice lacking A20 in DCs demonstrated spontaneous
      proliferation of conventional and double-negative T cells, their conversion to
      interferon-gamma (IFN-gamma)-producing effector cells, and expansion of plasma
      cells. They developed ds-DNA antibodies, nephritis, the antiphospholipid
      syndrome, and lymphosplenomegaly-features of systemic lupus erythematosus-and
      extramedullary hematopoiesis. A20-deficient DCs were resistant to apoptosis,
      caused by increased sensitivity to CD40L and RANKL prosurvival signals and
      upregulation of antiapoptotic proteins Bcl-2 and Bcl-x. They captured injected
      apoptotic cells more efficiently, resisted the inhibitory effects of apoptotic
      cells, and induced self-reactive effector lymphocytes. Because genetic
      polymorphisms in TNFAIP3 are associated with human autoimmune disorders, these
      findings identify A20-mediated control of DC activation as a crucial checkpoint
      in the development of systemic autoimmunity.

PMID- 21723157
TI  - Innate immune sensing of retroviral infection via Toll-like receptor 7 occurs
      upon viral entry.
AB  - Innate immune sensors are required for induction of pathogen-specific immune
      responses. Retroviruses are notorious for their ability to evade immune defenses
      and establish long-term persistence in susceptible hosts. However, some infected
      animals are able to develop efficient virus-specific immune responses, and thus
      can be employed for identification of critical innate virus-sensing mechanisms.
      With mice from two inbred strains that control retroviruses via adaptive immune
      mechanisms, we found that of all steps in viral replication, the ability to enter
      the host cell was sufficient to induce antivirus humoral immune responses. Virus
      sensing occurred in endosomes via a MyD88-Toll-like receptor 7-dependent
      mechanism and stimulated virus-neutralizing immunity independently of type I
      interferons. Thus, efficient adaptive immunity to retroviruses is induced in vivo
      by innate sensing of the early stages of retroviral infection.

PMID- 21723158
TI  - Signaling by the phosphatase MKP-1 in dendritic cells imprints distinct effector
      and regulatory T cell fates.
AB  - Naive T cells respond to antigens by differentiating into effector and regulatory
      lineages. Whereas the roles of T cell-intrinsic pathways have been extensively
      studied, how T cell lineage choices are controlled by innate immune signals
      remains elusive. Here we report that dendritic cell (DC)-expressed phosphatase
      MKP-1, a negative regulator of the MAP kinases, programmed reciprocal T helper 1
      (Th1) and Th17 cell differentiation by modulating IL-12-STAT4 and IL-6-STAT3 axes
      and cytokine receptor expression at the DC-T cell interface. MKP-1 was regulated
      by innate recognition signals and its deficiency disrupted antimicrobial
      responses and promoted T cell-mediated inflammation. Moreover, MKP-1 inhibited
      induction of regulatory T cells by downregulating TGF-beta2 production from DCs.
      Our findings identify a regulatory circuit linking MKP-1 signaling in DCs,
      production of polarizing cytokines, and integration of DC-derived signals in
      responding T cells, that bridges innate and adaptive immunity to coordinate
      protective immunity and immunopathology.

PMID- 21723159
TI  - A requisite role for induced regulatory T cells in tolerance based on expanding
      antigen receptor diversity.
AB  - Although both natural and induced regulatory T (nTreg and iTreg) cells can
      enforce tolerance, the mechanisms underlying their synergistic actions have not
      been established. We examined the functions of nTreg and iTreg cells by adoptive
      transfer immunotherapy of newborn Foxp3-deficient mice. As monotherapy, only
      nTreg cells prevented disease lethality, but did not suppress chronic
      inflammation and autoimmunity. Provision of Foxp3-sufficient conventional T cells
      with nTreg cells reconstituted the iTreg pool and established tolerance. In turn,
      acute depletion of iTreg cells in rescued mice resulted in weight loss and
      inflammation. Whereas the transcriptional signatures of nTreg and in vivo-derived
      iTreg cells were closely matched, there was minimal overlap in their T cell
      receptor (TCR) repertoires. Thus, iTreg cells are an essential nonredundant
      regulatory subset that supplements nTreg cells, in part by expanding TCR
      diversity within regulatory responses.

PMID- 21723160
TI  - A conventional preclinical schedule of cisplatin is more effective than a
      metronomic frequent bolus schedule for urothelial carcinoma.
AB  - OBJECTIVES: Given the frequent inability to administer a conventional 3-weekly
      schedule of cisplatin to human subjects with urothelial carcinoma, we evaluated a
      frequent bolus metronomic schedule in a preclinical system of transitional cell
      carcinoma (TCC) of the urothelium. We hypothesized that the anti-angiogenic and
      anti-cell-migratory activity of lower concentrations of cisplatin may confer
      similar anti-tumor activity and demonstrate less nephrotoxicity than conventional
      cytotoxic concentrations. MATERIALS AND METHODS: We evaluated the activity of
      cisplatin in vitro against human urothelial carcinoma (5637) and endothelial
      cells (human umbilical vein endothelial cells, HUVECs). The MTT assay was
      employed to assess viability, and flow cytometry with Annexin-FITC labeling was
      employed to assess apoptosis. Cell migration in monolayer culture was assessed by
      scratch assay. Murine xenografts (n = 12 per group) bearing measurable
      subcutaneous tumors of 5637 cells were administered either no therapy, cisplatin
      2 mg/kg/3 days a week (metronomic) or 6 mg/kg/ once a week (standard)
      intraperitoneal (i.p.) for 4 weeks. Blood was collected from 5 mice per group at
      baseline and at the end of therapy to measure changes in serum creatinine.
      RESULTS: Significant antiproliferative activity, but poor pro-apoptotic activity,
      was observed against 5637 urothelial carcinoma cells in vitro by MTT assay with
      cisplatin at concentrations lower than those attainable in vivo. Anti
      proliferative activity against HUVECs required higher concentrations than
      attainable in vivo. Anti-migratory activity was observed against 5637 and HUVECs
      at earlier time points and with concentrations lower than anti-proliferative
      concentrations. In murine 5637 xenografts, standard cisplatin was significantly
      better at inhibiting tumor growth than the no treatment control (P = 0.005),
      while metronomic therapy was not better than control (P = 0.22). Standard
      cisplatin was also significantly nephrotoxic (P = 0.016), while metronomic
      cisplatin (P = 0.374) or no therapy (P = 0.178) did not demonstrate significant
      nephrotoxicity compared with baseline. CONCLUSIONS: Cisplatin exhibited anti-cell
      migratory activity against urothelial carcinoma and endothelial cells at lower
      than cytotoxic concentrations. However, a standard preclinical schedule was
      better than control in vivo for inhibiting tumor growth, while a metronomic
      schedule was not better. Despite the lower nephrotoxicity of the metronomic
      schedule, its lower anti-tumor activity suggests that a standard clinical
      schedule of cisplatin should not be routinely substituted by a split schedule
      without definitive clinical data.

PMID- 21723161
TI  - NAT2 slow acetylation haplotypes are associated with the increased risk of betel
      quid-related oral and pharyngeal squamous cell carcinoma.
AB  - BACKGROUND: NAT2, the most important phase II metabolic enzyme for betel quid
      (BQ), might modify the risk of BQ-related oral and pharyngeal squamous cell
      carcinoma (OPSCC) in Taiwan. STUDY DESIGN: PCR-RFLP and TaqMan assay were
      conducted for genotyping of NAT2 in 172 OPSCC cases and 170 healthy controls who
      habitually chewed BQ. RESULTS: The genotypic and allelic type of T341C and C481T
      in NAT2 are associated with the risk of OPSCC. There were linear trends between
      increased risk of OPSCC and slowness of NAT2 acetylation haplotypes (P = .017),
      especially for young subjects (P < .001), light BQ chewers (P = .005), light
      smokers (P = .023), and alcohol drinkers (P = .001). The interactions on risk of
      OPSCC were found for NAT2 acetylation haplotypes with status of age, BQ chewing,
      and alcohol drinking. CONCLUSIONS: The NAT2 acetylation haplotypes might be
      genetic markers for risk of BQ-related OPSCC.

PMID- 21723163
TI  - Wilderness communications.
AB  - When an emergency situation arises in a remote location, the ability to
      communicate with outside sources of assistance can prove very valuable. This
      article reviews the different types of communications technologies available to
      individuals in remote locations, including satellite telephones, personal locator
      beacons, satellite messengers, cellular telephones, and the different licensed
      and non-licensed 2-way radio services available for personal use. It also
      discusses basic radio communications techniques, emergency communication,
      requesting ground or air casualty evacuation, and selecting communications
      devices for different applications.

PMID- 21723164
TI  - Sildenafil and bosentan improve arterial oxygenation during acute hypoxic
      exercise: a controlled laboratory trial.
AB  - OBJECTIVES: Sildenafil and, recently, bosentan have been reported to increase
      arterial saturation and exercise capacity at altitude. The mechanisms behind this
      are still poorly defined but may be related to attenuation of hypoxic pulmonary
      vasoconstriction (HPV) and improved gas exchange. This study was designed to
      examine and compare the effect of sildenafil and bosentan on pulmonary gas
      exchange during acute hypoxic exercise in a controlled laboratory setting.
      METHODS: Sixteen athletic university students (8 males, 8 females) were examined
      during exercise in a hypoxic chamber (11% oxygen) before and after the
      administration of either sildenafil (n=10) or bosentan (n=6). Respiratory and
      metabolic measurements were taken at rest and during increasing exercise
      intensity (up to 90% of their individual maximal oxygen uptake [VO(2)max]) in
      concert with arterial blood gas sampling. RESULTS: Both drugs resulted in small,
      but significant increases in arterial PO(2) (2-3 Torr) and O(2) saturation (3-4%)
      at rest and during hypoxic exercise, in both men and women. No significant
      changes in arterial PCO(2) or ventilation were seen at rest or during exercise in
      hypoxia; however, heart rate (both at rest and during exercise) was increased
      with both sildenafil and bosentan in both men and women. CONCLUSIONS: These data
      demonstrate that sildenafil and bosentan equally improve arterial oxygenation in
      acute hypoxia in both men and women, which could account for improved physical
      performance at altitude.

PMID- 21723165
TI  - A new technique for the treatment of transverse vaginal septum by Foley catheter.
AB  - We report a new surgical technique for the management of transverse vaginal
      septum in a 13-year-old girl who presented with abdominal pain. Imaging
      techniques yielded hematocolpos. The patient and her family refused vaginal
      surgery in order to preserve hymenal integrity for sociocultural beliefs. At
      laparotomy, a vertical incision was made on posterior vaginal wall. An artery
      forceps was introduced from the hymenal opening while preserving the hymenal
      integrity. The septum located on the upper third of vagina was perforated by the
      help of a forceps introduced from posterior vaginal wall via an abdominal route.
      A Foley catheter was introduced from the introitus toward the septal perforation
      and was held by the forceps. The balloon of the catheter was placed on the
      perforated septum and it was insufflated with 10 ml of fluid. The Foley catheter
      was in place for 2 weeks. After removal of the catheter, she received oral
      contraceptive pills for 3 months postoperatively. She had regular spontaneous
      menses on follow-up for 6 months duration.

PMID- 21723166
TI  - Aspergillosis: something more than an Aspergillus fumigatus question.

PMID- 21723167
TI  - Simultaneously changes in striatum dopaminergic and glutamatergic parameters
      following hypoxic-ischemic neuronal injury in newborn piglets.
AB  - Basal ganglia injury (BGI) is a type of perinatal hypoxic-ischemic (H-I) brain
      injury. Both malfunctions of glutamatergic and dopaminergic pathways in striatum
      were suggested to contribute to BGI. In current study, we investigated the
      imaging profile of glutamate (Glx) levels by proton magnetic resonance
      spectroscopy ((1)H-MRS), and the expression of dopamine D2 receptors (D2R) and
      dopamine transporter (DAT) by immunohistochemical staining in a newborn piglet
      model of H-I brain injury. We found that the number of striatal D2R positive
      neurons decreased following H-I brain injury, and the decrease in positive neuron
      number was consistent with the degree of striatum. Following H-I brain insult,
      the number of striatal DAT positive neurons and glutamate level were
      simultaneously increased initially, followed by a gradual decline toward control
      level. There was a positive correlation between the changes in striatal DAT
      positive neurons and glutamate level following H-I brain insults in newborn
      piglets. Our findings suggest that following H-I brain insult, striatal D2R
      positive neurons decreased due to neuron death; straital DAT initially increased
      to compensate for dopamine uptake; and glutamatergic and dopaminergic systems in
      striatum may act in an interdependent way in the striatum of newborn piglets.

PMID- 21723171
TI  - Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein
      HuR.
AB  - Posttranscriptional gene regulation relies on hundreds of RNA binding proteins
      (RBPs) but the function of most RBPs is unknown. The human RBP HuR/ELAVL1 is a
      conserved mRNA stability regulator. We used PAR-CLIP, a recently developed method
      based on RNA-protein crosslinking, to identify transcriptome-wide ~26,000 HuR
      binding sites. These sites were on average highly conserved, enriched for HuR
      binding motifs and mainly located in 3' untranslated regions. Surprisingly, many
      sites were intronic, implicating HuR in mRNA processing. Upon HuR knockdown, mRNA
      levels and protein synthesis of thousands of target genes were downregulated,
      validating functionality. HuR and miRNA binding sites tended to reside nearby but
      generally did not overlap. Additionally, HuR knockdown triggered strong and
      specific upregulation of miR-7. In summary, we identified thousands of direct and
      functional HuR targets, found a human miRNA controlled by HuR, and propose a role
      for HuR in splicing.

PMID- 21723170
TI  - Integrative regulatory mapping indicates that the RNA-binding protein HuR couples
      pre-mRNA processing and mRNA stability.
AB  - RNA-binding proteins coordinate the fates of multiple RNAs, but the principles
      underlying these global interactions remain poorly understood. We elucidated
      regulatory mechanisms of the RNA-binding protein HuR, by integrating data from
      diverse high-throughput targeting technologies, specifically PAR-CLIP, RIP-chip,
      and whole-transcript expression profiling. The number of binding sites per
      transcript, degree of HuR association, and degree of HuR-dependent RNA
      stabilization were positively correlated. Pre-mRNA and mature mRNA containing
      both intronic and 3' UTR binding sites were more highly stabilized than
      transcripts with only 3' UTR or only intronic binding sites, suggesting that HuR
      couples pre-mRNA processing with mature mRNA stability. We also observed HuR
      dependent splicing changes and substantial binding of HuR in polypyrimidine
      tracts of pre-mRNAs. Comparison of the spatial patterns surrounding HuR and miRNA
      binding sites provided functional evidence for HuR-dependent antagonism of
      proximal miRNA-mediated repression. We conclude that HuR coordinates gene
      expression outcomes at multiple interconnected steps of RNA processing.

PMID- 21723172
TI  - Dyspnoea and pulmonary consolidation in a cat with T-cell lymphoma.
AB  - A 13-year-old male neutered domestic shorthair cat presented with an acute onset
      of dyspnoea. Thoracic radiographs revealed marked, bilateral, caudal lung lobe
      consolidation. A diagnosis of anatomically mixed T-cell lymphoma with pulmonary,
      renal and alimentary involvement was confirmed on histopathology. Pulmonary
      involvement in cases of feline lymphoma is uncommon and the radiographic
      appearance of pulmonary lymphoma is highly variable. Lung lobe consolidation has
      been described with primary lung tumours in cats, but not previously in
      association with pulmonary lymphoma. This unusual presentation serves to alert
      practitioners to the possibility of lymphoma as a cause of severe
      bronchopulmonary disease in the cat.

PMID- 21723173
TI  - Dorsal spinous process impingement syndrome ('kissing spine') in a cat: imaging
      appearance and surgical management.
AB  - Spinal pain is an important clinical presentation in feline patients, but the
      underlying causes can often be difficult to elucidate. Dorsal spinous process
      impingement syndrome ('kissing spine' or in human patients 'Baastrup syndrome')
      is a significant cause of spinal pain in equine and human patients and
      radiographically is characterised by a close approximation of adjacent spinous
      processes with reactive bone sclerosis affecting these spinous processes. In this
      report we describe the first reported case of dorsal spinous process impingement
      syndrome in a cat causing spinal pain, and successful surgical management of the
      syndrome. The affected cat presented at 5 years of age for evaluation of a 7
      month history of progressive thoracolumbar pain. Radiographs revealed close
      approximation of the dorsal spinous processes of the seventh, eighth and ninth
      thoracic vertebrae (T7, T8 and T9), with associated reactive bone sclerosis.
      Surgical resection of the T8 dorsal spinous process resulted in complete
      resolution of the clinical signs with no evidence of recurrence 9 months after
      surgery.

PMID- 21723174
TI  - [Assessment of health care providers on family presence during resuscitation].

PMID- 21723175
TI  - [Attitudes and behaviour of women towards cardiovascular disease prevention].
AB  - OBJECTIVE: To find out the attitudes and behaviour of women towards preventive
      activities related to cardiovascular disease. METHOD: Cross-sectional descriptive
      study, through a self-completion questionnaire, in three Health Centres in Toledo
      (Spain). A total of 539 women between 18 and 65 years old answered an ad hoc
      developed questionnaire that contained items on knowledge, attitudes, and
      behaviours in preventive practices. RESULTS: The mean age was 40.4 years age; 361
      (66.7%) came from urban areas; 354 (65.4%) were married; 221 (40.8%) had
      university studies; 382 (70.8%) were working; 432 (83.2%) believed that the
      leading cause of death in women was cancer; 174 (32.4%) said they had annual
      preventive medical check-ups; 411 (76.8%) considered it very dangerous to smoke,
      but 159 (30.0%) currently smoked. Alcohol consumption was considered very
      dangerous by 232 (43.4%); 92 (17.2%) were regular consumers (almost every week).
      Only 128 (23.8%) did exercise one or more times per week. Only 127 (24.0%)
      followed some type of diet. At least one annual BP and laboratory tests
      (cholesterol and blood sugar) were measured in 68.4%, 64.1% and 53.9%,
      respectively. A total of 266 (51.7%) had been advised once on their lifestyle by
      a healthcare professional. CONCLUSIONS: The impact of cardiovascular disease in
      women is underestimated. Our population seemed concerned about the risk of
      certain habits but this was not always translated into a healthy lifestyle. It
      seems that our advice may not change the behaviour of women in many cases, but it
      does increase the number of clinical and analytical controls. We must insist on
      the prevention of cardiovascular risk in women and improve the effectiveness of
      our interventions.

PMID- 21723176
TI  - [Evaluation of an educational group intervention in the control of patients with
      cardiovascular risk].
AB  - OBJECTIVE: To compare an educational group intervention with individual care to
      improve clinical and management variables among patients with cardiovascular risk
      (CVR) in community health care (PC). METHODS: A randomised controlled
      experimental study was developed in 7 PC centres of Barcelona (Spain). A total of
      2,127 patients included in the chronic diseases protocol of the centres were
      selected. The intervention group (IG) attended four educative workshops led by
      their nurses during one year. Clinical and management variables (number of
      visits, pharmaceutical expenditure, nurse time consumption) were measured at
      baseline and 3 months after the intervention in the IG and in the control group
      (CG). Pre-post-intervention and IG vs. CG differences were analysed. RESULTS:
      Among the 672 patients belonging to the IG, 144 were lost due to failing to
      attend the workshops. CG (n=824) had no withdrawals. At the end of follow-up
      there were no significant differences between their clinical variables. The
      number of visits and pharmaceutical expenditure increased in the IG. However, the
      annual dedication of nurses per patient per year was 39.59 minutes in the IG and
      60 minutes in the CG. CONCLUSIONS: Nurse group control of patients with CVR in PC
      saves nurse-time compared with the usual individual visits. However, further
      studies are needed to better define what type of patient that is more susceptible
      to follow cardiovascular control through group workshops and whether this time
      saving is related to the use of other health resources.

PMID- 21723177
TI  - Association analysis of proopiomelanocortin (POMC) haplotypes in type 1 diabetes
      in a UK population.
AB  - AIM: To assess the association of POMC haplotype-tagged single nucleotide
      polymorphisms (htSNPs) with the development of type 1 diabetes (T1D) in a
      Caucasian population. METHODS: All exons, intron 1, and approximately 6-kb
      upstream and 3-kb downstream of the POMC gene were bidirectionally resequenced to
      identify DNA polymorphisms in 30 individuals. Allele frequencies were determined
      (60 chromosomes) and efficient htSNPs were selected using the htSNP2 programme.
      Genotyping was performed in 390 cases, 339 controls and 245 T1D parent-offspring
      trios, using Taqman, Sequenom and direct-sequencing technologies. RESULTS:
      Thirteen polymorphisms (two novel) with a minor allele frequency greater than 1%
      were identified. Six POMC htSNPs (rs3754863 G>A, ss161151662 A>G, rs3754860 C>T,
      rs1009388 G>C, rs3769671 A>C, rs1042571 G>A) were identified. Allele and
      haplotype frequencies were similar between case and control groups (P>0.60 by
      permutation test), and assessment of allele transmission distortion from
      informative parents to affected offspring also failed to find any association.
      Stratification of these analyses for age-at-onset and HLA-DR risk group (DR3/DR4)
      revealed no significant associations. A haplotype block of 9.86-kb from rs3754863
      to rs1042571 was identified, encompassing the POMC gene. Comparison of haplotype
      frequencies identified the GGCGAG haplotype as protective against T1D in 12.9% of
      cases vs. 18.3% of controls: chi(2)=8.18, Pc=0.03 by permutation test.
      CONCLUSION: The POMC SNP haplotype GGCGAG may have a protective effect against
      T1D in the UK population. However, this finding needs to be replicated, and the
      cellular and molecular processes influenced by this POMC haplotype determined to
      fully appreciate its impact.

PMID- 21723178
TI  - Ultrasound assisted one-pot, three-components synthesis of pyrimido[1,2
      a]benzimidazoles and pyrazolo[3,4-b]pyridines: A new access via phenylsulfone
      synthon.
AB  - A simple, facile, efficient and three-components procedure for the synthesis of
      pyrimido[1,2-a]benzimidazoles and pyrazolo[3,4-b]pyridines utilizing
      phenylsulfone synthon, under ultrasonic irradiation was developed.

PMID- 21723179
TI  - Competitive inhibition of transcription factors by small interfering peptides.
AB  - Combinatorial assortment by dynamic dimer formation diversifies gene
      transcriptional specificities of transcription factors. A similar but
      biochemically distinct mechanism is competitive inhibition in which small
      proteins act as negative regulators by competitively forming nonfunctional
      heterodimers with specific transcription factors. The most extensively studied is
      the negative regulation of auxin response factors by AUXIN/INDOLE-3-ACETIC ACID
      repressors. Similarly, Arabidopsis thaliana (Arabidopsis) little zipper and mini
      finger proteins act as competitive inhibitors of target transcription factors.
      Competitive inhibitors are also generated by alternative splicing and controlled
      proteolytic processing. Because they provide a way of attenuating transcription
      factors we propose to call them small interfering peptides (siPEPs). The siPEP
      mediated strategy could be applied to deactivate specific transcription factors
      in crop plants.

PMID- 21723180
TI  - Coupled parametric model for estimation of visual field tests based on OCT
      macular thickness maps, and vice versa, in glaucoma care.
AB  - The current standard of care for glaucoma patients consists of functional
      assessment of vision via visual field (VF) testing, which is sensitive but
      subjective, time-consuming, and often unreliable. A new imaging technology,
      Fourier domain optical coherence tomography (OCT), is being introduced to assess
      the structural characteristics of the macula. This new complementary exam is
      efficient, objective, and reliable. A complex, but consistent, relationship
      exists between the structural information provided by macular OCT and the
      functional information gathered by VF maps. We propose a learning-based framework
      with the ability to estimate the VF map based on OCT macular thickness
      measurements as input (and vice versa). Central to this algorithmic framework is
      a coupled parametric model that captures not only the individual variabilities of
      the OCT macular thickness measurements and the VF maps, but also their co
      dependencies. This model is derived by applying principal component analysis
      (PCA) to a library consisting of various pairs of OCT and VF maps. The parameters
      of this coupled model are obtained by solving a linear least squares problem.
      Next, these estimated parameters are used, in conjunction with the eigenvectors
      derived from PCA, to compute the estimate. The accuracy of this coupled
      parametric estimation model was evaluated by performing multiple leave-one-out
      cross validation experiments.

PMID- 21723181
TI  - Analysis and modification of surfaces using molecular ions in the ambient
      environment.
AB  - The analysis and modification of surfaces in their native conditions can be
      performed using new mass spectrometric methods. Ambient ionization sources,
      including desorption electrospray ionization (DESI), have been implemented for
      the rapid analysis of unmodified biological surfaces including whole plant
      material, tissue sections, algae, and bacterial colonies. Recent advances have
      shown promise for in vivo and high-throughput clinical analysis. Additionally,
      the recent development of ambient ion soft landing (SL) allows polyatomic ions to
      be deposited onto surfaces in open air. Ambient SL offers speed, control, and
      flexibility for surface reactions and modification.

PMID- 21723182
TI  - New insights in plant immunity signaling activation.
AB  - Plant disease resistance can be triggered by specific recognition of microbial
      effectors by plant nucleotide binding-leucine rich repeat (NB-LRR) receptors.
      Over the last few years, many efforts have greatly improved the understanding of
      effector and NB-LRR function, but have left a lot of questions as to how effector
      perception activates NB-LRR induction of defense signaling. This review describes
      exciting new findings showing similarities and differences in function of diverse
      plant NB-LRR proteins in terms of pathogen recognition and where and how
      resistance proteins are activated. Localization studies have shown that some NB
      LRRs can activate signaling from the cytosol while others act in the nucleus.
      Also, the structural determination of two NB-LRR signaling domains demonstrated
      that receptor oligomerization is fundamental for the activation of resistance
      signaling.

PMID- 21723183
TI  - A characterization study on 2,6-dimethyl-4-nitropyridine N-oxide by density
      functional theory calculations.
AB  - This study deals with the identification of a title compound, 2,6-dimethyl-4
      nitropyridine N-oxide by means of theoretical calculations. The optimized
      molecular structures, vibrational frequencies, corresponding vibrational
      assignments, thermodynamic properties and atomic charges of the title compound in
      the ground state were evaluated using density functional theory (DFT) with the
      standard B3LYP/6-311G(d,p) method and basis set combination for the first time.
      Theoretical vibrational spectra were interpreted with the aid of normal
      coordinate analysis based on scaled density functional force field. The results
      show that the optimized geometric parameters (bond lengths and bond angles) and
      vibrational frequencies were observed to be in good agreement with the available
      experimental results. Based on the results of comparison between experimental
      results and theoretical data, the chosen calculation level is powerful approach
      for understanding the molecular structures and vibrational spectra of the 2,6
      dimethyl-4-nitropyridine N-oxide. Moreover, we not only simulated frontier
      molecular orbitals (FMO) and molecular electrostatic potential (MEP) but also
      determined the transition state and energy band gap. Based on the investigations,
      the title compound is found to be useful to bond metallically and interact
      intermolecularly. Infrared intensities and Raman activities were also reported.

PMID- 21723184
TI  - Crystal growth, structural, optical, spectral and thermal studies of tris(L
      phenylalanine)L-phenylalaninium nitrate: a new organic nonlinear optical
      material.
AB  - Tris(L-phenylalanine)L-phenylalaninium nitrate, C(9)H(12)NO(2)(+).NO(3)(
      ).3C(9)H(11)NO(2) (TPLPN), a new organic nonlinear optical material was grown
      from aqueous solution by slow evaporation solution growth at room temperature.
      The grown crystals were subjected to powder X-ray diffraction and single crystal
      X-ray diffraction studies to confirm the crystalline nature and crystal
      structure. The modes of vibration of different molecular groups present in TPLPN
      have been identified by FTIR spectral analysis. The presence of hydrogen and
      carbon in the grown crystal were confirmed by using proton and carbon nuclear
      magnetic resonance (NMR) spectral analyses. The optical transmission spectral
      study establishes good transmitting ability of the crystal in the entire visible
      region. The thermogravimetric (TG) and differential thermal analyses (DTA) were
      carried out to understand the thermal stability of the sample. The nonlinear
      optical property of the compound observed using Kurtz powder second harmonic
      generation test assets the suitability of the grown material for the frequency
      conversion of laser radiation of Nd:YAG.

PMID- 21723185
TI  - Theoretical and infrared spectroscopy study of the conformational preferences for
      some 3-monosubstituted-2-methylpropenes.
AB  - The infrared spectra of 3-X-2-methylpropenes (X = Cl, Br, I, NMe(2), NEt(2), OH,
      OMe, OEt, SH, SMe and SEt) have been recorded at room temperature in CCl(4)
      solution. The C=C stretching mode was analyzed and compared to theoretically
      calculated data to give insight about the conformational isomerism of these
      compounds. A combination band systematically appears in all spectra (except for
      amines); the remaining nu(C=C) band and the corresponding intensities were used
      to obtain the conformer populations. For second-period atoms bonded to C-3, two
      or more conformers are observed in CCl(4) solution, but when substitution by
      heavier atoms takes place, only one conformer is observed under the tested
      conditions, i.e., the gauche form with respect to the C=C-C-X dihedral angle.
      Therefore, steric hindrance between X and =CH(2) in the s-cis form is strongly
      dependent on the heteroatom size, while the effect of the alkyl chain bonded to
      the heteroatom seems to be of secondary importance.

PMID- 21723186
TI  - Novel transition metal complexes of 4-hydroxy-coumarin-3-thiocarbohydrazone:
      pharmacodynamic of Co(III) on rats and antimicrobial activity.
AB  - A new series of stable transition metal complexes of the formula M(L)X.S, where M
      = Cu(II), Ni(II), Co(III), Cr(III) and Fe(III) and L is the deprotonated ligand
      of 4-hydroxy-coumarin-3-thiocarbohydrazone, X = Cl(-), NO(3)(-) or CH(3)COO(-)
      and S = H(2)O and/or EtOH. The HL ligand was prepared by the reaction of 3-formyl
      4-hydroxy-coumarine with thiocarbohydrazide in the molar ratio 1:1. The HL ligand
      and its metal complexes were characterized by elemental analysis, (1)H NMR, IR
      and electronic spectra, and molar conductance and magnetic measurements and
      thermal gravimetric analysis (TGA). The HL ligand acts as a monobasic tridentate
      ONS donor in all metal complexes, and coordinated through the phenolic OH,
      azomethine nitrogen and thione sulfur. Electronic spectra with magnetic moments
      suggested varieties of geometries around the central metal atoms. Thermal
      gravimetric analysis indicates that the complexes are stable up to 300 degrees C,
      and release the uncoordinated and/or coordinated H(2)O/solvent molecules, which
      is accompanied by a color change. The formed complexes after releasing the
      solvent were investigated and their structures are suggested to have square
      planar or octahedral arrangement. Pharmacodynamic of cobalt(III) complex on some
      biochemical parameters and histological studies in serum and heart tissue in rats
      have been studied. Although the complexes demonstrated a significant effect at
      low dose than the high dose, the ligand showed significant good effects in both
      high and low doses on the biochemical analysis in serum and heart tissue. Cobalt
      complex was screened in order to evaluate its antifungal activity against the
      filamentous fungi Aspergillus niger, Aspergillus fumigatus, and Aspergillus
      flavus, and antibacterial activity against the Candida albicans, Escherichia
      coli, Klebseilla pneumoniae and Pseudomonas aeruginosa.

PMID- 21723187
TI  - Absorption spectral analysis of 4f-4f transitions for the complexation of Pr(III)
      and Nd(III) with thiosemicarbazide in absence and presence of Zn(II) in aqueous
      and organic solvents.
AB  - The complexation of thiosemicarbazide with Pr(III) and Nd(III) in absence and
      presence of Zn(II), a soft metal ion in aqueous and organic solvents like
      CH(3)OH,CH(3)CN, dioxane (C(4)H(8)O(2)) and DMF (C(3)H(7)NO) and their equimolar
      mixtures are discussed by employing absorption difference and comparative
      absorption spectrophotometry. Complexation of thiosemicarbazide with Pr(III) and
      Nd(III) is indicated by the changes in the absorption intensity following the
      subsequent changes in the oscillator strength of different 4f-4f bands and Judd
      Ofelt intensity (T(lambda)) parameters. The other spectral parameters like energy
      interaction parameters namely Slater-Condon (F(k)), Racah (E(k)), Lande (xi(4f)),
      Nephelauxetic ratio (beta) and bonding parameters (b(1/2)) are further computed
      to explain the nature of complexation. The difference in the energy parameters
      with respect to donor atoms and solvents reveal that the chemical environment
      around the lanthanide ions has great impact on f-f transition and any change in
      the environment result in modification of the spectra. Various solvents and their
      equimolar mixtures are also used to discuss the participation of solvents in the
      complexation.

PMID- 21723188
TI  - Study on the structural changes of bovine serum albumin with effects on polydatin
      binding by a multitechnique approach.
AB  - Polydatin is a traditional Chinese medicine which shows effective biological
      activity as antimicrobial and antiviral agent. The secondary structure changes of
      bovine serum albumin (BSA) were investigated by the methods of Fourier transform
      infrared spectroscopy (FT-IR), circular dichroism (CD) and Raman spectroscopy.
      The experimental results indicated that polydatin changed the secondary structure
      of BSA. The presence of polydatin decreased alpha-helix content of BSA. The
      conformations of disulfide bridges and the microenvironment of Tyr, Trp residues
      were also changed.

PMID- 21723189
TI  - Chiral discrimination asserted by enantiomers of Ni (II), Cu (II) and Zn (II)
      Schiff base complexes in DNA binding, antioxidant and antibacterial activities.
AB  - Chiral Schiff base ligands (S)-H(2)L and (R)-H(2)L and their complexes (S-Ni-L, R
      Ni-L, S-Cu-L, R-Cu-L, S-Zn-L and R-Zn-L) were synthesized, characterized and
      examined for their DNA binding, antioxidant and antibacterial activities. The
      complexes showed higher binding affinity to calf thymus DNA with binding constant
      ranging from 2.0*10(5) to 4.5*10(6) M(-1). All the complexes also exhibited
      remarkable superoxide (56-99%) and hydroxyl scavenging (45-89%) activities as
      well as antibacterial activities against gram (+) and gram (-) bacteria. However,
      none of the complexes showed antifungal activity. Conclusively, S enantiomers of
      the complexes were found to be relatively more efficient for DNA interaction,
      antioxidant and antibacterial activities than their R enantiomers. This study
      reveals the possible utilization of chiral Schiff base complexes for
      pharmaceutical applications.

PMID- 21723190
TI  - Differences in findings of nocturnal polysomnography and multiple sleep latency
      test between narcolepsy and idiopathic hypersomnia.
AB  - OBJECTIVES: To compare differences in nocturnal and daytime polysomnographic
      findings between narcolepsy (NA) with and without cataplexy (CA) and idiopathic
      hypersomnia without long sleep time (IHS w/o LST). METHODS: Nocturnal
      polysomnography (n-PSG) and multiple sleep latency test (MSLT) findings were
      compared among subjects with NA with CA (n=52), NA without CA (n=62), and IHS w/o
      LST (n=50). RESULTS: The NA with CA group had significantly more disrupted and
      shallower nocturnal sleep than the other groups. On MSLT, the IHS w/o LST group
      had significantly longer sleep latency (SL) compared with the two NA groups. The
      latter two groups did not show statistical differences in diurnal variation of
      SL. CONCLUSIONS: The IHS w/o LST group had milder objective daytime sleepiness
      compared with the NA groups. In patients with NA, nocturnal sleep disturbances
      appeared only in cases with CA, despite a similar trend in diurnal changes in
      sleep propensity between the two NA groups. SIGNIFICANCE: Objective nocturnal
      sleep disturbances are specific to NA patients with CA, whereas diurnal
      variations of sleep propensity are observed irrespective of the presence of CA
      among NA patients. These findings could be helpful for choosing optimal treatment
      plans for patients with these disorders.

PMID- 21723191
TI  - Subulatomonas tetraspora nov. gen. nov. sp. is a member of a previously
      unrecognized major clade of eukaryotes.
AB  - While a large number of aerobic free-living protists have been described within
      the last decade, the number of new anaerobic or microaerophilic microbial
      eukaryotic taxa has lagged behind. Here we describe a microaerophilic genus and
      species of amoeboflagellate isolated from a near-shore marine site off the coast
      at Plymouth, Massachusetts: Subulatomonas tetraspora nov. gen. nov. sp. This
      taxon is closely related to Breviata anathema based on both microscopical
      features and phylogenetic analyses of sequences of three genes: SSU-rDNA, actin,
      and alpha-tubulin. However, Subulatomonas tetraspora nov. gen. nov. sp. and B.
      anathema are morphologically distinctive, differ by 14.9% at their SSU-rDNA
      locus, and were isolated from marine and 'slightly brackish' environments,
      respectively. Phylogenetic analyses of these two taxa plus closely related
      sequences from environmental surveys provide support for a novel clade of
      eukaryotes that is distinct from the major clades including the Opisthokonta,
      Excavata, Amoebozoa and 'SAR' (Stramenopile, Alveolate, Rhizaria).

PMID- 21723192
TI  - Sterols of the green-pigmented, aberrant plastid dinoflagellate, Lepidodinium
      chlorophorum (Dinophyceae).
AB  - Lepidodinium chlorophorum is a green-pigmented dinoflagellate with an aberrant,
      tertiary plastid of chlorophyte ancestry rather than the typical red algal,
      secondary endosymbiont found in the vast majority of photosynthetic
      dinoflagellates. To date, only one published study exists on the galactolipids of
      L. chlorophorum, with nothing known about other lipid classes, including sterols.
      Our objectives were to examine the sterol composition of L. chlorophorum to
      determine if it produces any unique sterols with the potential to serve as
      biomarkers, and to compare it to members of the Chlorophyceae to determine if it
      has inherited any signature green algal sterols from its chlorophyte-derived
      endosymbiont. We have found that L. chlorophorum produces 6 sterols, all with a
      4alpha-methyl substituent and none of which are known to occur in the
      Chlorophyceae. Rather, the sterols produced by L. chlorophorum place it within a
      group of dinoflagellates that have the common dinoflagellate sterols, dinosterol
      and dinostanol, as part of their sterol composition.

PMID- 21723193
TI  - Phylogenetic analyses of a combined data set suggest that the Attheya lineage is
      the closest living relative of the pennate diatoms (Bacillariophyceae).
AB  - A Bayesian analysis of a seven gene data set was conducted to reconstruct
      phylogenetic relationships among a sample of centric and pennate diatoms and to
      test alternative hypotheses about the closest living relative of
      Bacillariophyceae. A lineage, composed of two Attheya species, was inferred to
      share the most recent common ancestor with Bacillariophyceae--a relationship that
      was also corroborated by the combined parsimony analysis. All competing
      hypotheses about the closest living relative of Bacillariophyceae were rejected
      because 100% of the trees in the post-burn-in sample in the Bayesian analysis
      supported the Attheya-Bacillariophyceae clade. According to a partitioned Bremer
      support analysis, the majority of the genes in the combined data matrix supported
      the Attheya--Bacillariophyceae relationship. The global topology of the
      phylogenetic tree indicated that a monophyletic group consisting of
      Thalassiosirales and Toxarium undulatum formed the deepest branch followed by a
      node uniting a clade composed of Bacillariophyceae/Attheya species and a lineage
      made up of Eucampia zoodiacus, Chaetocerotales, Lithodesmiales, Triceratiales,
      Biddulphiales and Cymatosirales. Except for the phylogenetic positions of
      Lithodesmiales, Thalassiosira sp and Skeletonema costatum, the optimal tree
      obtained from the combined parsimony analysis showed the same branching order of
      taxa as those seen in the consensus tree inferred from three independent Markov
      chain Monte Carlo analyses. Noteworthy findings are that Toxarium undulatum
      shares a strongly supported node with Thalassiosirales and that the genus Attheya
      is not a member of the Chaetocerotales lineage.

PMID- 21723194
TI  - Characterization of Pharyngomonas kirbyi (= "Macropharyngomonas halophila" nomen
      nudum), a very deep-branching, obligately halophilic heterolobosean flagellate.
AB  - The tetraflagellate Pharyngomonas is among the most commonly reported morphotypes
      of halophilic protozoa. We have established two cultures of Pharyngomonas kirbyi,
      SD1A and AS12B, from 3000/00 and 2100/00 salinity waters from the USA and
      Australia, respectively. 18S rRNA gene phylogenies confirm that Pharyngomonas is
      the same entity as 'Macropharyngomonas' (nomen nudum), and represents the deepest
      branch in the heterolobosean lineage. Pharyngomonas kirbyi (Strain SD1A) has
      flattened/discoidal cristae, and lacks conspicuous Golgi dictyosomes. It also has
      a heterolobosean 'double bikont' flagellar apparatus, with two right roots, each
      associated with an 'I' fibre and part of a rhizoplast-like complex. One right
      root splits shortly after its origin, and supplies most of the microtubules that
      support both the ventral groove, and the sub-anterior cytopharynx. Interestingly,
      Pharyngomonas has some potentially ancestral features not found in typical
      Heterolobosea, including elongated left roots associated with multilayered 'C'
      fibres, orthogonal basal bodies, and a spur structure that might represent a 'B'
      fibre homolog. Both isolates are obligate halophiles that grow best at 100
      2000/00 salinity and do not grow below 750/00 salinity. Pharyngomonas is
      therefore of considerable evolutionary importance, both as a deep-branching,
      plesiomorphic heterolobosean, and a borderline extreme halophile.

PMID- 21723195
TI  - Modeling complex neuropsychiatric disorders with human induced pluripotent stem
      cells.
AB  - Identifying the molecular and cellular basis of complex neuropsychiatric
      disorders (cNPDs) has been limited by the inaccessibility of central neurons,
      variability within broad diagnostic classifications, and the interplay of genetic
      and environmental factors. Recent work utilizing neuronally differentiated human
      induced pluripotent stem cells (hiPSCs) from Mendelian and polygenic cNPDs is
      beginning to illuminate neuritic, synaptic or cell body variations accompanied by
      specific gene or protein expression alterations largely mimicking known
      pathology. In some cases, phenotypes have only emerged after application of
      cellular stress or long duration of differentiation. Pathological and cellular
      expression features are fully or partially responsive to pharmacological
      treatment highlighting the potential utility of differentiated hiPSCs for
      discovery of personalized therapeutics and for identifying pathogenetically
      relevant targets in subgroups of patients within a broad syndromic
      classification. Because of the inherent variability in developing and
      differentiating hiPSC lines and the multiple comparisons implicit in 'omics'
      technologies, rigorous algorithms for assuring statistical significance and
      independent confirmation of results, will be required for robust modeling of
      cNPDs.

PMID- 21723196
TI  - Kell hemolytic disease of the fetus. Combination treatment with plasmapheresis
      and intrauterine blood transfusion.
AB  - We report the case of a 36-year old pregnant woman with a Kell alloimmunization
      (anti-K1), probably secondary to a previous blood transfusion, and a severe
      hemolytic disease of the fetus. Once the first fetal blood transfusion by
      cordocentesis was performed, we started treatment with repeated plasmapheresis to
      maintain anti-K1 titer below 1:32. With this scheme we did not need to perform a
      second intrauterine fetal blood transfusion and only mild anemia was found in the
      newborn. Taking into account that the rate of serious complications with
      plasmapheresis is lower than that related with intrauterine blood transfusion,
      this could be an alternative approach to repeated transfusions.

PMID- 21723197
TI  - In vitro production of red blood cells.
AB  - Blood transfusion is a mainstay of modern clinical medicine. However, a number of
      fundamental problems persist, including insufficiency of supply, the threat of
      transfusion transmissible infectious disease and the problem of immune
      incompatibility. It would be extremely valuable, therefore, to develop a
      potentially limitless, infection free, immune neutral source of erythrocytes for
      transfusion. Human embryonic stem cells (hESC), have potentially limitless
      proliferative capacity and the potential to differentiate into the majority of
      adult cell types including erythrocytes. A number of barriers to the development
      of clinical cellular therapeutics from hESC have been posited, including HLA
      incompatibility between donor and recipient, difficulties in defining optimal
      cell phenotype and function in vitro and the fact that most tissues consist of
      complex three-dimensional matrices of cells. Many or most of these problems are
      circumvented in the generation of erythrocytes and group O RhD negative Kell
      negative blood would be compatible with the majority of recipients. Red cell
      transfusion is therefore an attractive goal for pluripotent stem cell derived
      therapeutics. Much progress has been made however, a number of challenges remain
      including scale up, ensuring clinical effectiveness and product safety.

PMID- 21723198
TI  - Management options for cervical intraepithelial neoplasia.
AB  - Management of cervical intraepithelial neoplasia (CIN) needs to protect women at
      risk from developing cervical cancer and to avoid over-treatment as well as
      obstetrical complications in women undergoing invasive treatment. Strong evidence
      shows that CIN3 is a true precursor and must be treated, whereas CIN1 lesions do
      not benefit from immediate surgery and should be followed conservatively.
      Although the clinical course of CIN2 differs from CIN3, it should be treated the
      same way for legal reasons. Colposcopy plays a central role in selection of
      patients and treatments. Treatment of CIN2 and 3 should be excisional. Large loop
      excision of the transformation zone, high-frequency-needle or laser conisation
      are equally good, whereas cold-knife conisation is associated with an excess risk
      for subsequent obstetrical complications. Human papillomavirus testing and
      cytology at 6 months seems to be the best post-treatment monitoring, although
      this needs to be confirmed by randomised-controlled trials. Future research needs
      to focus more on how the quality of colposcopy and the overall management concept
      determines the clinical outcome instead of exploring the role of single technical
      methods. Furthermore, it seems to be necessary to evaluate the best management of
      CIN2 in young and in vaccinated women.

PMID- 21723199
TI  - Endogenous opioids released during non-nociceptive environmental stress induce
      latent pain sensitization Via a NMDA-dependent process.
AB  - Although stress induces analgesia, there is evidence that stressful events may
      exacerbate pain syndromes. Here, we studied the effects of 1 to 3 prestressful
      events (days 0, 2, and 7), such as non-nociceptive environmental stress, on
      inflammatory hyperalgesia induced by a carrageenan injection (day 14) in 1 rat
      hind paw. Changes in nociceptive threshold were evaluated by the paw pressure
      vocalization test. The higher the number of stress sessions presented to the
      rats, the greater was the inflammatory hyperalgesia. Blockade of opioid receptors
      by naltrexone before each stress inhibited stress-induced analgesia and
      suppressed the exaggerated inflammatory hyperalgesia. Stressed versus nonstressed
      animals could be discriminated by their response to a fentanyl ultra-low dose
      (fULD), that produced hyperalgesia or analgesia, respectively. This
      pharmacological test permitted the prediction of the pain vulnerability level of
      prestressed rats because fULD analgesic or hyperalgesic indices were positively
      correlated with inflammatory hyperalgesic indices (r(2) = .84). In prestressed
      rats, fULD-induced hyperalgesia and the exaggerated inflammatory hyperalgesia
      were prevented NMDA receptor antagonists. This study provides some preclinical
      evidence that pain intensity is not only the result of nociceptive input level
      but is also dependent on the individual history, especially prior life stress
      events associated with endogenous opioid release. PERSPECTIVE: Based on these
      preclinical data, it would be of clinical interest to evaluate whether prior
      stressful events may also affect further pain sensation in humans. Moreover, this
      preclinical model could be a good tool for evaluating new therapeutic strategies
      for relieving pain hypersensitivity.

PMID- 21723200
TI  - Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid
      transformation.
AB  - Somatic loss-of-function mutations in the ten-eleven translocation 2 (TET2) gene
      occur in a significant proportion of patients with myeloid malignancies. Although
      there are extensive genetic data implicating TET2 mutations in myeloid
      transformation, the consequences of Tet2 loss in hematopoietic development have
      not been delineated. We report here an animal model of conditional Tet2 loss in
      the hematopoietic compartment that leads to increased stem cell self-renewal in
      vivo as assessed by competitive transplant assays. Tet2 loss leads to a
      progressive enlargement of the hematopoietic stem cell compartment and eventual
      myeloproliferation in vivo, including splenomegaly, monocytosis, and
      extramedullary hematopoiesis. In addition, Tet2(+/-) mice also displayed
      increased stem cell self-renewal and extramedullary hematopoiesis, suggesting
      that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo.

PMID- 21723201
TI  - TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and
      is a recurrent event during human lymphomagenesis.
AB  - Loss-of-function mutations affecting one or both copies of the Ten-Eleven
      translocation (TET)2 gene have been described in various human myeloid
      malignancies. We report that inactivation of Tet2 in mouse perturbs both early
      and late steps of hematopoiesis including myeloid and lymphoid differentiation in
      a cell-autonomous manner, endows the cells with competitive advantage, and
      eventually leads to the development of malignancies. We subsequently observed
      TET2 mutations in human lymphoid disorders. TET2 mutations could be detected in
      immature progenitors endowed with myeloid colony-forming potential. Our results
      show that the mutations present in lymphoid tumor cells may occur at both early
      and later steps of lymphoid development and indicate that impairment of TET2
      function or/and expression predisposes to the development of hematological
      malignancies.

PMID- 21723202
TI  - Use of diazoxide in management of severe postprandial hypoglycemia in patient
      after Roux-en-Y gastric bypass.

PMID- 21723203
TI  - Short-term medication cost savings for treating hypertension and diabetes after
      gastric bypass.
AB  - BACKGROUND: The cost of medication for the treatment of hypertension and diabetes
      in the morbidly obese is a significant economic healthcare burden. In the present
      study, we assessed the effect of gastric bypass surgery on the average annual
      costs for hypertension and diabetes medication. METHODS: A prospective database
      of gastric bypass patients at the Palo Alto Veterans Affairs Health Care System
      was reviewed. The preoperative and postoperative medication requirements to treat
      hypertension and diabetes were identified before surgery and at 1 year
      postoperatively. Comparisons were made between the annual costs of the
      antihypertensive and diabetic medications before and after bariatric surgery
      using the Student paired t test. RESULTS: Of 106 patients who had undergone
      gastric bypass, 90 (85%) had either hypertension or diabetes. Of these 90
      patients, 88 (98%) had hypertension and 60 (67%) had diabetes before surgery.
      Complete remission of hypertension occurred in 44% and remission of diabetes in
      80% at 1 year after surgery. The annual cost of medications to treat hypertension
      was reduced by 65% at 1 year after surgery ($63.52 compared with $20.50, P <
      .0001). To treat diabetes, the annual medication cost was reduced by 88% at 1
      year after gastric bypass surgery ($532.06 compared with $64.58, P < .0001). In
      the subset of patients with persistent hypertension or diabetes after surgery,
      the annual cost reduction for antihypertensive medications was 58% ($87.14 versus
      $36.82, P < .002). The annual cost reduction for diabetic medications was 69%
      ($1036.60 versus $322.90, P < .02). CONCLUSION: Gastric bypass surgery resulted
      in a significant reduction in the cost of medications to treat hypertension and
      diabetes in the morbidly obese at 1 year after surgery. These cost savings were
      also significant in the subset of patients who had persistent hypertension and
      diabetes after surgery.

PMID- 21723204
TI  - Symptoms of depression in a minority population of women from an urban obstetrics
      and gynecology clinic.
AB  - OBJECTIVE: The aim of this exploratory study was to determine and compare the
      rates of depressive symptoms across 3 groups of African-American and Hispanic
      pregnant, postpartum, and nonperipartum gynecology patients in a hospital-based
      urban outpatient obstetrics and gynecology clinic. METHOD: Seventy-eight subjects
      were recruited from the outpatient department of an inner city hospital. Each
      subject completed the Beck Depression Inventory. RESULTS: Rates of depressive
      symptoms were high in all groups. Results, although not significant, indicated a
      worsening depression in the nonperipartum gynecology group compared with that in
      the obstetric sample. Affective components of the Beck Depression Inventory were
      significantly higher in the gynecology group than in the peripartum groups.
      CONCLUSION: We have identified an important clinical population of nonperipartum
      gynecology patients in need of diagnosis and treatment. Early identification of
      depression in women is an important strategy in which primary health workers have
      an important role.

PMID- 21723205
TI  - Magnetic resonance imaging-measured atrophy and its relationship to cognitive
      functioning in vascular dementia and Alzheimer's disease patients.
AB  - BACKGROUND: Recent pathological studies report vascular pathology in clinically
      diagnosed Alzheimer's disease (AD) and AD pathology in clinically diagnosed
      vascular dementia (VaD). We compared magnetic resonance imaging (MRI) measures of
      vascular brain injury (white matter hyperintensities [WMH] and infarcts) with
      neurodegenerative measures (medial-temporal atrophy [MTA] and cerebral atrophy
      [CA]) in clinically diagnosed subjects with either AD or VaD. We then examined
      relationships among these measures within and between the two groups and their
      relationship to mental status. METHODS: Semi-quantitative MRI measures were
      derived from blind ratings of MRI scans obtained from participants in a research
      clinical trial of VaD (N = 694) and a genetic epidemiological study of AD (N =
      655). RESULTS: CA was similar in the two groups, but differences in the mean of
      MTA and WMH were pronounced. Infarcts were significantly associated with CA in
      VaD but not in AD; MTA and WMH were associated with CA in both. WMH was
      associated with MTA in both groups; however, MRI infarcts were associated with
      MTA in VaD but not with MTA in AD patients. MTA was strongly associated with Mini
      Mental State Examination scores in both groups, whereas evidence of a modest
      association between WMH and Mini-Mental State Examination scores was seen in VaD
      patients. CONCLUSIONS: MRI data from two dementia cohorts with differing dementia
      etiologies find that the clinical consequences of dementia are most strongly
      associated with cerebral and medial-temporal atrophy, suggesting that tissue loss
      is the major substrate of the dementia syndrome.

PMID- 21723206
TI  - Frequency of Alzheimer's disease pathology at autopsy in patients with clinical
      normal pressure hydrocephalus.
AB  - BACKGROUND: Normal pressure hydrocephalus (NPH) is considered to be potentially
      treatable with the placement of a cerebrospinal fluid (CSF) shunt. However, the
      procedure has been reported to have variable success, particularly with respect
      to improving the cognitive impairment in NPH. The presence of neurologic
      comorbidities, particularly Alzheimer's disease (AD), may contribute to shunt
      responsiveness. Uncovering the extent to which AD and NPH co-occur has
      implications for diagnosis and treatment of NPH. Autopsy studies of patients with
      NPH during their lifetime would elucidate the frequency of such comorbidities.
      METHODS: A search of the Sun Health Research Institute Brain Donation Program
      database was conducted between January 1, 1997 and April 1, 2009 to identify all
      cases with neuropathologic evidence of dementia as well as those of clinically
      diagnosed NPH. We reviewed the medical records and brain findings of each NPH
      case. RESULTS: Of the 761 cases autopsied over the study interval, 563 were found
      to have neuropathologic evidence meeting criteria for a dementing illness. Of 563
      cases, AD was found exclusively in 313 (56%), and 94 suffered from secondary
      diagnosis of dementia. Nine of 761 cases were identified with a clinical
      diagnosis of NPH, which were among the 563 cases with neuropathology of dementing
      illness at autopsy, representing 1.6% (9/563) of the cases. On review of brain
      autopsy reports of these nine patients, eight (89%) were found to have AD and one
      (11%) had progressive supranuclear palsy. Review of the medical records of the
      nine NPH cases revealed the following clinical comorbidities: five suffered from
      AD, one from Parkinson's Disease, one from mild cognitive impairment, and one
      from seizure disorder. CONCLUSIONS: Given the findings of the present study, we
      support the AD-NPH theory and posit that AD is a common pathologic comorbidity in
      the setting of NPH and may preclude cognitive improvement postshunt placement.
      This may influence the selection of cases for shunting in the future.

PMID- 21723207
TI  - Efficient DNA interstrand crosslinking by 6-thioguanine and UVA radiation.
AB  - Patients taking the immunosuppressant and anticancer thiopurines 6
      mercaptopurine, azathioprine or 6-thioguanine (6-TG), develop skin cancer at a
      very high frequency. Their DNA contains 6-TG which absorbs ultraviolet A (UVA)
      radiation, and their skin is UVA hypersensitive, consistent with the formation of
      DNA photodamage. Here we demonstrate that UVA irradiation of 6-TG-containing DNA
      causes DNA interstrand crosslinking. In synthetic duplex oligodeoxynucleotides,
      the interstrand crosslinks (ICLs) can form between closely opposed 6-TG bases
      and, in a less favoured reaction, between 6-TG and normal bases on the opposite
      strand. In vivo, UVA irradiation of cultured cells containing 6-TG-substituted
      DNA also causes ICL formation and induces the chromosome aberrations that are
      characteristically associated with this type of DNA lesion. 6-TG/UVA activates
      the Fanconi anemia (FA) pathway via monoubiquitination of the FANCD2 protein.
      Cells defective in the FA pathway or other factors involved in ICL processing,
      such as XPF and DNA Polzeta, are all hypersensitive to killing by 6-TG/UVA
      consistent with a significant contribution of photochemical ICLs to the
      cytotoxicity of this treatment. Our findings suggest that sunlight-exposed skin
      of thiopurine treated patients may experience chronic photochemical DNA damage
      that requires constant intervention of the FA pathway.

PMID- 21723208
TI  - Determination of hexamethylene bisacetamide, an antineoplastic compound, in mouse
      and human plasma by LC-MS/MS.
AB  - Hexamethylene bisacetamide (HMBA) is a polar compound which has recently been
      discovered to have antineoplastic activity by up-regulating the expression of an
      endogenous antiproliferative breast cancer protein, HEXIM1 (hexamethylene
      bisacetamide inducible protein 1) in vivo. HMBA has been shown in the past to
      induce terminal differentiation in multiple leukemia types at a concentration of
      2-5mM, but its phase I and II clinical trials were largely unsuccessful due to
      serious side effects (notably, thrombocytopenia) with dose escalation. In this
      work, a sensitive and simple LC-MS/MS method for direct determination of HMBA in
      mouse and human plasma is described. Plasma samples were prepared by
      deproteinization with acetonitrile. Separation was achieved on a Waters
      Atlantis((r)) T3 (2.1 mm * 50 mm, 3 MUm) column with retention times of 2.2 and
      3.7 min for HMBA and 7MBA (internal standard), respectively. The quantitation was
      carried out by tandem mass spectrometry using positive MRM mode. The linear range
      of the method was 0.500-100 ng/mL in both mouse and human plasma with injection
      volume of 5 MUL. This method has been validated in accordance with the US Food
      and Drug Administration (FDA) guidelines for bioanalytical method development and
      applied to the determination of HMBA concentrations in FVB mice over time after a
      single dose of HMBA in saline (0.9% NaCl) at 10mg/kg.

PMID- 21723209
TI  - Quantitative measurement of plasma free metanephrines by ion-pairing solid phase
      extraction and liquid chromatography-tandem mass spectrometry with porous
      graphitic carbon column.
AB  - Plasma free metanephrine and normetanephrine are the best biomarkers for
      diagnosing pheochromocytoma. In the past few years, liquid chromatography-tandem
      mass spectrometry has become the preferred technology to measure plasma
      metanephrine and normetanephrine because of its high sensitivity and specificity,
      as well as fast and simple sample preparation. In this study, we report a liquid
      chromatography-tandem mass spectrometry method for measuring plasma metanephrine
      and normetanephrine. A solid phase extraction method using ion-pairing reagent
      and C18 stationary phase was used for sample preparation. We tested a porous
      graphitic carbon column and a HILIC column for chromatographic separation, and
      the former one showed better resolution with no interference from plasma matrix.
      This method was linear from 7.2-486.8 pg/mL for metanephrine and 18.0-989.1 pg/mL
      for normetanephrine with an accuracy of 92.2-111.8% and 92.1-115.0%,
      respectively. Inter-assay and intra-assay CV for metanephrine and normetanephrine
      at two different concentration levels ranged from 2.0% to 10.9%. In conclusion,
      this liquid chromatography-tandem mass spectrometry method using ion-pairing
      solid phase extraction and porous graphitic column was simple and efficient for
      measuring plasma metanephrines.

PMID- 21723210
TI  - Simultaneous quantification of carbamate insecticides in human plasma by liquid
      chromatography/tandem mass spectrometry.
AB  - Carbofuran (CFN), carbosulfan (CSN) and fenobucarb (FBC) are carbamate pesticides
      that are widely used in gardening and agriculture for the control of insects.
      Human poisoning due to occupational or self-poisoning exposures is also reported,
      so assays are required to quantify the plasma concentration of these
      insecticides. An LC-MS/MS method was developed and validated for the simultaneous
      quantification of these three carbamate insecticides in the plasma of patients
      with acute intentional self-poisoning. Plasma samples were pretreated by
      acetonitrile for protein precipitation. Chromatography was carried out on a Luna
      C18(2) analytical column with gradient elution using a mobile phase containing
      acetonitrile and water with 10mM ammonium acetate. Mass spectrometric analysis
      was performed by an Applied Biosystems MDS Sciex API 2000 triple quadrupole mass
      spectrometer coupled with electrospray ionization (ESI) source in the positive
      ion mode. The total run time was 7 min. The assay was validated over a
      concentration range from 10 to 1000 ng/ml for CSN and FBC and 20-2000 ng/ml for
      CFN. The precision and accuracy for both intra- and inter-day determination of
      all analytes were acceptable (<15%). No significant matrix effect was observed.
      Stability of compounds was established for short term bench and autosampler
      storage as well as freeze/thaw cycles. The method was effectively applied to 270
      clinical samples from patients with a history of acute intentional carbamate self
      poisoning.

PMID- 21723211
TI  - D-Amino acids in aged proteins: analysis and biological relevance.
AB  - Homochirality is essential for life. L-Amino acids are exclusively used as
      substrates for the polymerization and formation of peptides and proteins in
      living systems. However, d-amino acids, which are enantiomers of L-amino acids,
      were recently detected in various living organisms in the form of free D-amino
      acids and D-amino acid residues in peptides and proteins. In particular, D
      aspartyl (Asp) residues have been detected in various proteins from diverse
      tissues of elderly individuals. Here, we describe three important aspects of our
      research: (i) a method for detecting D-beta-Asp at specific sites in particular
      proteins, (ii) a likely spontaneous mechanism by which Asp residues in proteins
      invert and isomerize to the D-beta-form with age under physiological conditions,
      (iii) a discussion of factors that favor such a reaction.

PMID- 21723212
TI  - [Gallbladder torsion: a rare entity].

PMID- 21723213
TI  - Invited commentary.

PMID- 21723214
TI  - MtDNA diversity of Ghana: a forensic and phylogeographic view.
AB  - West Africa is characterized by a migration history spanning more than 150,000
      years. Climate changes but also political circumstances were responsible for
      several early but also recent population movements that shaped the West African
      mitochondrial landscape. The aim of the study was to establish a Ghanaian mtDNA
      dataset for forensic purposes and to investigate the diversity of the Ghanaian
      population sample with respect to surrounding populations. We sequenced full
      mitochondrial control regions of 193 Akan people from Ghana and excluded two
      apparently close maternally related individuals due to preceding kinship testing.
      The remaining dataset comprising 191 sequences was applied as etalon for quasi
      median network analysis and was subsequently combined with 99 additional control
      region sequences from surrounding West African countries. All sequences were
      incorporated into the EMPOP database enriching the severely underrepresented
      African mtDNA pool. For phylogeographic considerations, the Ghanaian haplotypes
      were compared to those of 19 neighboring populations comprising a total number of
      6198 HVS1 haplotypes. We found extensive genetic admixture between the Ghanaian
      lineages and those from adjacent populations diminishing with geographical
      distance. The extent of genetic admixture reflects the long but also recent
      history of migration waves within West Africa mainly caused by changing
      environmental conditions. Also, evidence for potential socio-economical
      influences such as trade routes is provided by the occurrence of U6b and U6d
      sequences found in Dubai but also in Tunisia leading to the African West Coast
      via Mauritania and Senegal but also via Niger, Nigeria to Cameroon.

PMID- 21723215
TI  - Calcitonin use in giant cell bone tumors.
AB  - INTRODUCTION: As osteoclast, giant cell tumors express calcitonin receptors. The
      aim of this paper is to assess treatment using salmon calcitonin after curettage.
      MATERIAL AND METHODS: We retrospectively reviewed 25 patients with giant cell
      tumor of the appendicular skeleton treated with a single protocol of calcitonin
      administration following curettage in order to assess the effectiveness of
      calcitonin in reducing the rate of local recurrence. RESULTS: The mean duration
      follow-up was 68 months. Thirteen patients (52%) had local recurrence. Eight of
      them were treated successfully after repeated curettage and calcitonin. Four
      patients had bone resection and one patient had curettage and cement filling. All
      patients with cavity left empty had ossified and the functional score as assessed
      by the MSTS score was 28.02/30. CONCLUSION: This study suggests that the use of
      calcitonin as adjuvant is not effective and that filling agents are not required
      after curettage of giant cell tumors. LEVEL OF EVIDENCE: Level 4.

PMID- 21723216
TI  - Hydatid cyst open in biliary tract: therapeutic approaches. Report of 22 cases.
AB  - GOAL: Discuss the different therapeutic options based on results of a series of
      patients undergoing operation for hydatid cyst ruptured into the biliary tract.
      PATIENTS AND METHODS: This was a retrospective study of 22 patients operated on
      between 2001 and 2007 for hydatid cyst ruptured into the biliary tract. RESULTS:
      The mean age of patients was 37 years old. There were 14 men and eight women.
      Cholangitis was present in 59% of patients and isolated pain in the right upper
      quadrant was found in 20% of patients. Procedures performed included internal
      fistula drainage through the sphincter of Oddi (37.3%), cystobiliary
      disconnection by percutaneous transhepatic cystocholedochostomy (27.3%), bipolar
      drainage (27.3%), direct suture closure of the fistula (9.1%). The postoperative
      course was uneventful in 15 patients. Specific morbidity concerned four patients.
      An external biliary fistula and suppuration of the residual cavity was observed
      in two patients each. One patient died. Median survival was 24 months. No
      recurrence or late complications were seen in this series. CONCLUSION: The
      management of hydatid cyst ruptured into the biliary tract is not consensual.
      Radical treatment is best because it provides definitive treatment of both the
      fistula and the cyst at the same time. However, conservative treatment is the
      preferred treatment in endemic countries. The choice of the technique depends of
      the experience of the surgeon, as well as local and topographic conditions. The
      best treatment remains preventive by eradication of echinococcosis.

PMID- 21723217
TI  - The anti-estrogenic activity of sediments from agriculturally intense watersheds:
      assessment using in vivo and in vitro assays.
AB  - The goal of the current study was to determine whether sediments from
      agriculturally intense watersheds can act as a potential source of anti
      estrogenic endocrine-disrupting compounds. The specific objectives of the current
      study were to determine (1) whether female fathead minnows (Pimephales promelas)
      experience alterations in endocrine function when exposed to sediments collected
      from agriculturally intense watersheds and (2) if these sediments display anti
      estrogenic activity in an in vitro assay. In addition, sediment samples were
      analyzed for the presence of steroid hormones and pesticides associated with
      local agricultural practices. To accomplish this, sediments and water were
      collected from three sites within two agriculturally intense Nebraska watersheds
      (Bow Creek and the Elkhorn River). In 2009, minnows were exposed to sediment
      and/or water collected from the two Bow Creek sites (East Bow Creek and the
      Confluence) in the laboratory, while in 2010, minnows were exposed to sediment
      and/or water from East Bow Creek, the Confluence and the Elkhorn River. Following
      the 7-day exposure period, the hepatic mRNA expression of two-estrogen responsive
      genes, estrogen receptor alpha (ERalpha) and vitellogenin (Vtg) was determined.
      In 2009, females exposed to Confluence sediments, in the presence of laboratory
      water or Confluence water, experienced significant reductions in ERalpha
      expression relative to unexposed and Confluence water-exposed females. The
      defeminization of these females suggests the presence of a biologically available
      anti-estrogenic compound in sediments collected from this site. In 2010,
      sediments were assessed for anti-estrogenic activity on days 0 and 7 of the
      exposure period using a 4-h yeast estrogen screen. Lipophilic extracts (LEs) of
      day 0 sediments collected from the Confluence and the Elkhorn River induced
      significant reductions in the estrogenic reporter activity of treated yeast
      cultures suggesting the presence of a lipophilic anti-estrogenic compound in
      these extracts. Chemical analysis revealed the presence of a variety of steroid
      hormones, including those associated with the production of beef cattle (i.e.
      beta-trenbolone, alpha-zearalanol and alpha-zearalenol), in sediments indicating
      that compounds utilized by local beef cattle operations are capable of entering
      nearby watersheds. Overall, the results of this study indicate that an
      environmentally relevant anti-estrogenic compound is present in sediments from
      agriculturally intense watersheds and that this compound is bioavailable to fish.
      Furthermore, the presence of steroid hormones in sediments from these watersheds
      provides evidence indicating that steroids are capable of sorbing to sediments.

PMID- 21723218
TI  - Risk factors for progression of low-grade dysplasia in patients with Barrett's
      esophagus.
AB  - BACKGROUND & AIMS: Data vary on the progression of low-grade dysplasia (LGD) in
      patients with Barrett's esophagus (BE); in patients with LGD, we investigated the
      incidence of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) and
      compared progression in patients with different forms of LGD (prevalent vs
      incident and multifocal vs unifocal). We assessed the effects of consensus
      diagnosis of LGD on progression rates to HGD and EAC among expert pathologists.
      METHODS: In a multicenter outcomes project, 210 patients with BE and LGD
      (classified as incident, prevalent, or persistent) were included. Patients were
      followed up for an average of 6.2 years (959.6 patient-years). Persistent LGD was
      defined as detection of LGD on >=2 consecutive occasions during the follow-up
      period and extent as either unifocal (LGD at one level of BE segment) or
      multifocal (>1 level). Histology specimens were reviewed by 2 blinded
      pathologists. RESULTS: Six patients developed EAC (incidence of 0.44%/year), and
      21 developed HGD (incidence of 1.6%/year). The incidence of the combination of
      HGD and EAC was 1.83%/year. There were no associations between presence of
      prevalent, incident, or persistent LGD and the extent of LGD with progression
      rates. Based on consensus diagnosis of 88 reviewed specimens, there was no
      difference in the progression of LGD to either EAC (the incidence based on
      analyses by the local pathologist was 0.18%/year, the incidence when there was
      agreement between the local and one central pathologist was 0.21%/year, and the
      incidence when all 3 pathologists were in agreement was 0.39%/year) or combined
      HGD and EAC (0.94%/year, 0.87%/year, and 0.84%/year, respectively). CONCLUSIONS:
      Overall, patients with BE and LGD have a low annual incidence of EAC, similar to
      nondysplastic BE. There are no risk factors for progression and there is
      significant interobserver variation in diagnosis, even among expert pathologists.

PMID- 21723219
TI  - Prevalence of spontaneous portosystemic shunts in patients with portopulmonary
      hypertension and effect on treatment.
AB  - BACKGROUND & AIMS: We documented the frequency of large spontaneous portosystemic
      shunts in patients with moderate or severe portopulmonary hypertension (POPH) and
      determined the association between large shunts and response to treatment.
      METHODS: We performed a retrospective case-control study of data from patients
      with mild (mean pulmonary artery pressure [MPAP], 25-35 mm Hg; n = 18), moderate
      (MPAP, 35-50 mm Hg; n = 45), and severe POPH (MPAP, >50 mm Hg; n = 16). Data were
      compared with those from controls (normal echocardiography with estimated right
      ventricular systolic pressure, <35 mm Hg; n = 122). Spontaneous portosystemic
      shunts greater than 10 mm in diameter, identified by computed tomography or
      magnetic resonance, were classified as large. Response to treatment at 6 months
      was defined by right ventricular systolic pressure or MPAP as significant (<35 mm
      Hg), partial (35-50 mm Hg), or no response (>50 mm Hg). RESULTS: The frequency of
      spontaneous shunts did not differ significantly between groups of subjects with
      severe (n = 14 of 16), moderate (n = 38 of 45), or mild POPH (n = 11 of 18) or
      normal echocardiograms (controls, n = 86 of 122) (P = .77). Large shunts were
      associated with severe (14 of 16) and moderate POPH (32 of 45), compared with
      mild POPH (6 of 18) or controls (30 of 122) (P < .01). In 13 patients with severe
      POPH, large shunts were associated with lack of response to treatment in 90% (8
      of 9) or partial response in 50% (2 of 4). Among 27 patients with moderate POPH,
      large shunts were associated with no response to treatment in 13 of 19 (68%) and
      a partial response in 2 of 6 (33%). CONCLUSIONS: Large spontaneous portosystemic
      shunts are associated significantly with moderate and severe POPH, and with lack
      of response to treatment.

PMID- 21723220
TI  - Early mucosal healing with infliximab is associated with improved long-term
      clinical outcomes in ulcerative colitis.
AB  - BACKGROUND & AIMS: In the Active Ulcerative Colitis Trial (ACT)-1 and ACT-2,
      patients with ulcerative colitis treated with infliximab were more likely than
      those given placebo to have a clinical response, undergo remission, and have
      mucosal healing. We investigated the association between early improvement (based
      on endoscopy) and subsequent clinical outcome. METHODS: Patients underwent
      endoscopic evaluations at weeks 0, 8, 30, and 54 (ACT-1 only), and were
      categorized into 4 subgroups by week 8 (Mayo endoscopy subscore, 0-3). The
      association of week 8 endoscopy subscores, subsequent colectomy risk, symptoms
      and corticosteroid use outcomes were analyzed. Mucosal healing was defined as a
      Mayo endoscopy subscore of 0 (normal) or 1 (mild). RESULTS: Infliximab-treated
      patients with lower week 8 endoscopy subscores were less likely to progress to
      colectomy through 54 weeks of follow-up evaluation (P=.0004). This trend was not
      observed among patients given placebo (P=.47). Patients with lower endoscopy
      subscores achieved better symptomatic and corticosteroid use outcomes at weeks 30
      and 54 (P<.0001, infliximab; P<.01, placebo). Among patients who achieved
      clinical response at week 8, trends in subsequent clinical outcomes by week 8
      endoscopy subscores were generally consistent with that for the overall patient
      population; no trends were observed among patients who achieved clinical
      remission. CONCLUSIONS: The degree of mucosal healing after 8 weeks of infliximab
      was correlated with improved clinical outcomes including colectomy. Similar
      trends were observed for all outcomes except colectomy among the subgroup with
      clinical response at week 8. The degree of mucosal healing at week 8 among those
      in clinical remission did not predict subsequent disease course.

PMID- 21723222
TI  - Intestinal dendritic cells specialize to activate transforming growth factor-beta
      and induce Foxp3+ regulatory T cells via integrin alphavbeta8.
AB  - BACKGROUND & AIMS: The intestinal immune system is tightly regulated to prevent
      responses against the many nonpathogenic antigens in the gut. Transforming growth
      factor (TGF)-beta is a cytokine that maintains intestinal homeostasis, in part by
      inducing Foxp3(+) regulatory T cells (Tregs) that suppress immune responses. TGF
      beta is expressed at high levels in the gastrointestinal tract as a latent
      complex that must be activated. However, the pathways that control TGF-beta
      activation in the intestine are poorly defined. We investigated the cellular and
      molecular pathways that control activation of TGF-beta and induction of Foxp3(+)
      Tregs in the intestines of mice to maintain immune homeostasis. METHODS: Subsets
      of intestinal dendritic cells (DCs) were examined for their capacity to activate
      TGF-beta and induce Foxp3(+) Tregs in vitro. Mice were fed oral antigen, and
      induction of Foxp3(+) Tregs was measured. RESULTS: A tolerogenic subset of
      intestinal DCs that express CD103 were specialized to activate latent TGF-beta,
      and induced Foxp3(+) Tregs independently of the vitamin A metabolite retinoic
      acid. The integrin alphavbeta8, which activates TGF-beta, was significantly up
      regulated on CD103(+) intestinal DCs. DCs that lack expression of integrin
      alphavbeta8 had reduced ability to activate latent TGF-beta and induce Foxp3(+)
      Tregs in vitro and in vivo. CONCLUSIONS: CD103(+) intestinal DCs promote a
      tolerogenic environment in the intestines of mice via integrin alphavbeta8
      mediated activation of TGF-beta.

PMID- 21723221
TI  - Notch1 regulates the effects of matrix metalloproteinase-9 on colitis-associated
      cancer in mice.
AB  - BACKGROUND & AIMS: Inflammatory bowel disease increases the risks of colon cancer
      and colitis-associated cancer (CAC). Epithelial cell-derived matrix
      metalloproteinase (MMP)-9 mediates inflammation during acute colitis and the
      cleavage and activation of the transcription factor Notch1, which prevents
      differentiation of progenitor cells into goblet cells. However, MMP-9 also
      protects against the development of CAC and acts as a tumor suppressor. We
      investigated the mechanisms by which MMP-9 protects against CAC in mice. METHODS:
      C57/B6 wild-type mice were given a single dose of azoxymethane and 2 cycles of
      dextran sulfate sodium (DSS). Mice were also given the gamma-secretase inhibitor
      difluorophenacetyl-l-alanyl-S-phenylglycine t-butyl ester (DAPT) or dimethyl
      sulfoxide (control) during each DSS cycle; they were killed on day 56. We
      analyzed embryonic fibroblasts isolated from wild-type and MMP-9-/- mice and
      HCT116 cells that were stably transfected with MMP-9. RESULTS: Wild-type mice
      were more susceptible to CAC following inhibition of Notch1 by DAPT, shown by
      increased numbers of tumors and level of dysplasia compared with controls.
      Inhibition of Notch1 signaling significantly reduced protein levels of active
      Notch1, p53, p21WAF1/Cip1, Bax-1, active caspase-3, as well as apoptosis,
      compared with controls. Similar results were observed in transgenic HCT116 cells
      and embryonic fibroblasts from MMP-9-/- mice on gamma-radiation-induced damage of
      DNA. CONCLUSIONS: MMP-9 mediates Notch1 signaling via p53 to regulate apoptosis,
      cell cycle arrest, and inflammation. By these mechanisms, it might prevent CAC.

PMID- 21723223
TI  - Smoking and NASH: a hidden message from the GREACE trial.

PMID- 21723224
TI  - NCI, NHLBI first international consensus conference on late effects after
      pediatric hematopoietic cell transplantation: state of the science, future
      directions.

PMID- 21723225
TI  - EBMT risk score predicts outcome of allogeneic hematopoietic stem cell
      transplantation in patients who have failed a previous transplantation procedure.
AB  - Increasing numbers of allogeneic hematopoietic stem cell transplantation (allo
      SCT) are being performed for patients who have failed a previous allogeneic or
      autologous SCT. We investigated whether the EBMT risk score could predict outcome
      after a subsequent allo-SCT. We analyzed prognostic factors in 124 consecutive
      patients who underwent a second transplantation using an allogeneic donor at our
      institution. Patients with either a first autologous (N = 64) or first allogeneic
      (N = 60) SCT were included. Age, disease stage, time interval from diagnosis to
      transplantation, donor type, and donor-recipient sex combination were used to
      establish a score from 0 to 7 points, from which 3 groups were identified. The 5
      year survival probability decreased from 51.7% for risk scores 0-3 (low, n = 25),
      to 29.3% for risk score 4 (intermediate, n = 42), and only 10.4% for risk scores
      5-7 (high, n = 57), P = .001. We propose that the EBMT risk score can identify
      patients most likely to benefit from a second transplantation.

PMID- 21723226
TI  - Video imaging of the gastrointestinal tract in a patient with juvenile polyposis
      syndrome.

PMID- 21723227
TI  - Indolent primary aortoduodenal fistula presenting as iron deficiency anemia.

PMID- 21723228
TI  - Transarterial chemoembolization-induced main duct stricture.

PMID- 21723229
TI  - GI bleeding, colon varicosities, and visceral enlargement as a manifestation of
      Klippel-Trenaunay syndrome.

PMID- 21723230
TI  - Common bile duct carcinoid mimicking the clinical, EUS, and ERCP findings of
      cholangiocarcinoma: a rare but potentially curable cause of obstructive jaundice.

PMID- 21723231
TI  - The submucosal cushion does not improve the histologic evaluation of adenomatous
      colon polyps resected by snare polypectomy.
AB  - BACKGROUND & AIMS: Although the "submucosal cushion" technique or injection
      assisted polypectomy (IAP) is often used to resect colon polyps, little is known
      on the influence of this technique on histologic interpretation. We aimed to
      evaluate whether the use of a submucosal cushion improves the histologic and
      margin evaluation of colon polyps. METHODS: Consecutive patients undergoing
      polypectomy with and without IAP were included. An experienced blinded
      gastrointestinal pathologist evaluated the specimens using standardized criteria.
      RESULTS: One hundred eleven sessile colon adenomas were analyzed (IAP, n = 65,
      standard, n = 46). Two-thirds of polyps ranged in size from 10 to 20 mm; the
      average polyp size was 13.2 mm for IAP and 9.9 mm for standard snare polypectomy
      (P = .001). The cautery degree, cautery amount, and margin evaluability, did not
      differ substantially with regard to the resection technique. For polyps >=10-20
      mm, the overall architecture quality was better in polyps resected with standard
      technique as compared with IAP. CONCLUSIONS: The utilization of IAP did not
      result in a better margin evaluability of the resected polyp. Overall, IAP does
      not result in a better histologic polyp evaluability.

PMID- 21723232
TI  - Colonic perforation during percutaneous endoscopic gastrostomy tube insertion
      with subsequent bumper migration into colon.

PMID- 21723233
TI  - Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by
      pancreatic duct stenting: should it be routine?

PMID- 21723234
TI  - Fetoscopic documentation of meconium passage at 19 weeks' gestation.

PMID- 21723235
TI  - Combined pharyngeal impedance-manometry: has it finally come of age?

PMID- 21723236
TI  - Low risk of gastrointestinal cancer among patients with celiac disease,
      inflammation, or latent celiac disease.
AB  - BACKGROUND & AIMS: Celiac disease has been associated with gastrointestinal (GI)
      cancers in small studies; risks have not been estimated from large populations or
      based on histopathology analyses. METHODS: We examined the risk of GI cancers by
      using data from cohorts of patients with celiac disease (villous atrophy, Marsh
      score of 3; n = 28,882) or inflammation (Marsh score of 1-2; n = 12,860); biopsy
      samples were evaluated at 28 pathology centers. A third cohort included 3705
      individuals with latent celiac disease (normal mucosa, but positive serology
      results). Data were compared with those from an age- and sex-matched population.
      RESULTS: Of patients with celiac disease, 372 developed incident GI cancers; 347
      patients with inflammation and 38 with latent celiac disease developed GI
      cancers. In the first year after diagnosis and initial biopsy, celiac disease was
      associated with 5.95-fold increase in risk of incident GI cancer (95% confidence
      interval [CI], 4.64-7.64); the hazard ratio [HR] for inflammation was 9.13 (95%
      CI, 7.19-11.6) and for latent celiac disease was 8.10 (95% CI, 4.69-14.0). After
      the first year, patients were at no significant increase in risk for GI cancers;
      the HR for celiac disease was 1.07 (95% CI, 0.93-1.23), for inflammation it was
      1.16 (95% CI, 0.98-1.37), and for latent celiac disease it was 0.96 (95% CI, 0.56
      1.66). The absolute risk for any GI cancer in patients with celiac disease was
      101/100,000 person-years, with an excess risk of 2/100,000 person-years.
      CONCLUSIONS: Although celiac disease, inflammation, and latent disease all
      increase risk for GI cancers in the first year after diagnosis, there is no
      increase in risk thereafter.

PMID- 21723237
TI  - Management of patients following detection of unsuspected colon lesions by PET
      imaging.
AB  - Positron emission tomography (PET) is a well-established and integral component
      of multimodality imaging in oncology. However, the expanded use of PET in
      oncological and also non-oncological imaging (such as in assessing inflammatory
      conditions) has identified more lesions or tumors at unsuspected locations, such
      as in the large bowel during examination of patients not known to have colorectal
      disease. We review the clinical significance of colon lesions that were
      discovered incidentally by PET imaging and management strategies for
      gastroenterologists.

PMID- 21723238
TI  - Incidence of acute pancreatitis does not increase during Oktoberfest, but is
      higher than previously described in Germany.
AB  - BACKGROUND & AIMS: Increased alcohol consumption can lead to acute pancreatitis
      (AP). We investigated whether the incidence of alcohol-induced AP increased
      during the Munich Oktoberfest in 2008, at which 6.6 million liters of beer were
      sold within 16 days. METHODS: We performed a multicenter, prospective study of
      188 patients with AP (36.7% alcohol-induced, 34.6% biliary), treated at 27
      hospitals in the greater area of Munich, Germany (2,970,000 inhabitants) during
      the 2008 Oktoberfest. Data were compared with that from two 18-day control
      periods. RESULTS: During the Oktoberfest, the overall incidence of AP was
      42.8/100,000 person-years, which is 117% higher than previously reported. The
      incidence of acute attacks of alcoholic pancreatitis (AAP) did not increase
      during the Oktoberfest, compared with control periods. AAP was independently
      associated with repeated episodes of AP (P = .001), high levels of chronic
      alcohol intake (P = .001), low body-mass index (P = .007), male gender (P =
      .033), and acute alcohol excess (P = .037). Biliary AP was associated with
      increased levels of alanine-aminotransferase and aspartate-aminotransferase (P =
      .003), old age (P = .014), and low levels of chronic alcohol intake (P = .032).
      Death (5/188 patients) was associated with baseline levels of blood urea
      nitrogen, receiver operating characteristic-area under the curve (ROC-AUC =
      0.918), alkaline phosphatase (ROC-AUC = 0.861), and C-reactive protein (ROC-AUC =
      0.855). CONCLUSIONS: The incidence of AP does not increase during the
      Oktoberfest, compared with other time periods; the incidence of AP in Munich is
      higher than previously described in Germany. AAP was associated with long-term,
      heavy alcohol exposure rather than short-term, excessive alcohol drinking. Levels
      of blood urea nitrogen were associated with mortality.

PMID- 21723239
TI  - An unusual cause of dysphagia.

PMID- 21723240
TI  - High-frequency powers hidden within QRS complex as an additional predictor of
      lethal ventricular arrhythmias to ventricular late potential in post-myocardial
      infarction patients.
AB  - BACKGROUND: Ventricular late potentials (VLPs) have been known to be a predictor
      of lethal ventricular arrhythmias (L-VAs); however, detection of other
      arrhythmogenic signals within the QRS complex remains obscure. OBJECTIVE: The aim
      of this study was to evaluate whether abnormal intra-QRS high-frequency powers
      (IQHFP) within the QRS complex become a new predictor of L-VAs in addition to
      VLPs. METHODS: Both 12-lead electrocardiograms (ECG) and VLPs were recorded from
      142 subjects, including 37 patients without heart diseases, 97 patients post
      myocardial infarction (MI), and 45 post-MI patients with L-VAs. Time-frequency
      analysis of ECG (leads V(1) or II) using wavelet transform with the Morlet
      function was performed. After the time-frequency powers were calculated, the
      ratios of the peak of signal power during the QRS complex in high-frequency bands
      against the peak power at 80 Hz (b/a ratio; P100, P150, P200, P250, or
      P300Hz/P80Hz) were measured. Abnormal IQHFP was defined when the b/a ratio
      exceeded the optimal cut-off values estimated by receiver-operator characteristic
      curves. RESULTS: The combination of abnormal IQHFP appearing at 200, 250, and 300
      Hz with positive VLPs increased the sensitivity for prediction of L-VAs from
      53.3% by VLPs to 89.5%, and the negative predictive value from 74.7% by VLPs to
      87.7%. CONCLUSION: The combined use of VLPs and IQHFP hidden within the QRS
      complex improved the prediction of L-VAs in post-MI patients.

PMID- 21723241
TI  - Clinical phenotype and diagnosis of arrhythmogenic right ventricular
      cardiomyopathy in pediatric patients carrying desmosomal gene mutations.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an
      inherited heart muscle disease carrying a risk of sudden death. Information about
      the clinical features during childhood and the age at disease onset is scanty.
      OBJECTIVE: The aim of the study was to describe the ARVC phenotype as its initial
      clinical manifestation in a pediatric population (<18 years) with desmosomal gene
      mutations. METHODS: Fifty-three ARVC desmosomal gene mutation carriers (mean age
      12.3 +/- 3.9 years) were investigated by electrocardiogram (ECG), signal-averaged
      ECG, 24-hour Holter, echocardiogram, and contrast-enhanced cardiac magnetic
      resonance (CMR). RESULTS: None of the children <=10 years old fulfilled the 1994
      criteria, as opposed to six (33%) aged 11-14 years and eight aged >14 years
      (42%). At the end of follow-up (9 +/- 7 years), 21 (40%) fulfilled the 1994
      diagnostic criteria (mean age 16 +/- 4 years). By using the 2010 criteria in
      subjects aged <=18 years, 53% were unaffected, versus 62% by using the
      traditional criteria. More than two-thirds of affected subjects had moderate
      severe forms of the disease. Contrast-enhanced CMR was performed in 21 (40%); of
      13 unaffected gene mutation carriers, six showed ARVC morphological and/or tissue
      abnormalities. CONCLUSION: In pediatric ARVC mutation carriers, a diagnosis was
      achieved in 40% of cases, confirming that the disease usually develops during
      adolescence and young adulthood. The 2010 modified criteria seem to be more
      sensitive than the 1994 ones in identifying familial pediatric cases. Contrast
      enhanced CMR can provide diagnostic information on gene mutation carriers not
      fulfilling either traditional or modified criteria. Management of asymptomatic
      gene mutation carriers remains the main clinical challenge.

PMID- 21723242
TI  - Magnetic resonance imaging of superparamagnetic iron oxide-labeled macrophage
      infiltrates in acute-phase renal ischemia-reperfusion mouse model.
AB  - Macrophages play a key role in the initial pathogenesis of kidney ischemia
      reperfusion (I-R) injury, but the mechanism of their spatial and temporal
      recruitment from circulation remains uncertain. This study aimed to evaluate the
      feasibility of magnetic resonance imaging (MRI) for detecting intravenously
      administered superparamagnetic iron oxide (SPIO)-labeled macrophages in an
      experimental renal I-R mouse model. Unilateral kidney I-R mice were imaged with a
      4.7-T MRI scanner before and after administration of SPIO-labeled macrophages
      (RAW 264.7). On MR images, adoptive transfer of SPIO-labeled macrophages in the
      acute phase (1-2 days after I-R) caused a band-shaped signal-loss zone resulting
      from macrophage infiltrations, in the outer medullary region of injured kidneys.
      MRI detection of macrophages homing to an injured kidney may facilitate early
      detection and investigation of the pathogenesis of acute kidney injury and be a
      strategy for determining the treatment of acute renal failure. From the Clinical
      Editor: This study evaluated the feasibility of magnetic resonance imaging for
      detecting superparamagnetic iron oxide (SPIO)-labeled macrophages in a renal
      ischemia-reperfusion mouse model. Similar strategies in humans may facilitate
      early detection and stratification of acute kidney injury.

PMID- 21723243
TI  - Highly electroconductive multiwalled carbon nanotubes as potentially useful tools
      for modulating calcium balancing in biological environments.
AB  - Aiming to explore the mechanisms modulating cell-carbon nanotube interactions, we
      investigated whether Ca(2+) ion balancing between intra- and extracellular
      environments could be affected by multiwalled carbon nanotubes (MWCNTs). We
      analyzed the effects induced by two different kinds of MWCNTs (as prepared and
      annealed at 2400 degrees C) on the intracellular Ca(2+) ion levels in rat
      electrically sensitive cells and on the intercellular junction integrity of rat
      adenocarcinoma colon cells and platelet aggregation ability, which depend on the
      Ca(2+) concentration in the medium. MWCNTs, purified by annealing and more
      electroconductive as compared to nonannealed MWCNTs, affected Ca(2+) ion
      balancing between extra- and intracellular environments and induced changes on
      Ca(2+) ion-dependent cellular junctions and platelet aggregation, behaving as the
      calcium chelator ethylene glycol tetraacetic acid. This could be due to the
      sorption of cationic Ca(2+) ions on CNTs surface because of the excess of
      negatively charged electrons on the aromatic units formed on MWCNTs after
      annealing. From the ClinicAL Editor: The authors investigated whether Ca(2+) ion
      balance between intra- and extracellular space can be modulated by multiwalled
      carbon nanotubes (MWCNTs). Annealed nanotubes induced changes on Ca(2+) dependent
      cellular junctions and platelet aggregation, behaving similary to ethylene glycol
      tetraacetic acid, an established calcium chelator.

PMID- 21723244
TI  - Acquired loss of renal nuclease activity is restricted to DNaseI and is an organ
      selective feature in murine lupus nephritis.
AB  - An acquired loss of renal DNaseI promotes transformation of mild mesangial lupus
      nephritis into membranoproliferative end-stage organ disease. In this study, we
      analyzed expression profiles of DNaseI in other organs of lupus-prone (NZB*NZW)F1
      mice during disease progression to determine whether silencing of the renal
      DNaseI gene is an organ-specific feature or whether loss of DNaseI reflects a
      systemic error in mice with sever lupus nephritis. The present results
      demonstrate normal or elevated levels of DNaseI mRNA and enzyme activity in
      liver, spleen, and serum samples from (NZB*NZW)F1 mice throughout all the stages
      of lupus nephritis. DNaseI activity was dramatically reduced only in kidneys of
      mice with sever nephritis and was the only nuclease that was down-regulated,
      whereas six other nucleases (DNaseII1 to 3, caspase-activated DNase, Dnase2a, and
      endonuclease G) were approximately normally expressed in kidneys, liver, and
      spleen. Loss of renal DNaseI was not accompanied by changes in serum DNaseI
      activity, suggesting independent mechanisms of DNaseI regulation in circulation
      and in kidneys and an absence of compensatory up-regulation of serum DNaseI
      activity in the case of renal DNaseI deficiency. Thus, silencing of renal DNaseI
      is a unique renal feature in membranoproliferative lupus nephritis. Determining
      the mechanism(s) responsible for DNaseI down-regulation might lead to the
      generation of new therapeutic targets to treat and prevent progressive lupus
      nephritis.

PMID- 21723245
TI  - Changes in tumor growth and metastatic capacities of J82 human bladder cancer
      cells suppressed by down-regulation of calreticulin expression.
AB  - Bladder cancer is a common urothelial cancer. Through proteomic approaches,
      calreticulin (CRT) was identified and proposed as a urinary marker for bladder
      cancer. CRT is a multifunctional molecular chaperone that regulates various
      cellular functions such as Ca(2+) homeostasis and cell adhesion. CRT is
      overexpressed in various cancers, but its mechanism of action in the development
      of bladder tumors remains unclear. We generated J82 bladder cancer cells lines
      that either stably overexpressed or knocked down CRT to investigate the
      physiological effects of CRT on bladder tumors. Compared with the transfected
      control vector cells, the knockdown of CRT suppressed cell proliferation,
      migration, and attachment, whereas overexpression of CRT enhanced cell migration
      and attachment. We further demonstrated that the phosphorylation status of focal
      adhesion kinase and paxillin, important regulators of the focal adhesion complex,
      was also regulated in these cells. In contrast, phosphorylation of Src, a protein
      tyrosine kinase reported to be affected by CRT, was not significantly different
      between the control and CRT-RNAi groups. Most importantly, we observed that
      tumors derived from J82 CRT-RNAi cells were significantly smaller and had fewer
      metastatic sites in the lung and liver in vivo than did transfected control
      vector cells. In conclusion, our results suggest that alteration of CRT
      expression levels might affect bladder cancer progression in vitro and in vivo.

PMID- 21723247
TI  - Calpain inhibitors stimulate phagocyte functions via activation of human formyl
      peptide receptors.
AB  - Calpain inhibitors induce pertussis toxin (PTx)-sensitive chemotaxis in human
      neutrophils and monocytes. Here, we show that various calpain inhibitors
      (PD150606, PD151746, N-acetyl-Leu-Leu-Nle-CHO [ALLN], N-acetyl-Leu-Leu-Met-CHO
      [ALLM], and calpeptin) and gamma-secretase inhibitor I induced PTx-sensitive
      increase in cytoplasmic free Ca(2+) ([Ca(2+)](i)) in human neutrophils and
      neutrophil migration. HEK-293 cells stably expressing human formyl peptide
      receptor (hFPR) or hFPR-like 1 (hFPRL1) displayed stimulus-specific increase in
      [Ca(2+)](i) in response to calpain inhibitors (PD150606, PD151746, ALLN, ALLM, MG
      132, and calpeptin), gamma-secretase inhibitor I, and N-formyl-Met-Leu-Phe.
      Parent HEK-293 cells also displayed PTx-sensitive increase in [Ca(2+)](i) in
      response to calpeptin and gamma-secretase inhibitor I, whereas they displayed PTx
      resistant increase in [Ca(2+)](i) in response to MG-132. MDL-28170 induced
      neither an increase in [Ca(2+)](i) in neutrophils and HEK-293 cells nor
      neutrophil migration. Ionomycin-induced cleavage of talin (a substrate of
      calpain) in neutrophils was inhibited by all inhibitors used here. These findings
      suggest that potent calpain inhibitors could stimulate phagocyte functions via
      activation of hFPR, hFPRL1 and/or other G-protein coupled receptors depending on
      the inhibitors used.

PMID- 21723246
TI  - Renal accumulation of biglycan and lipid retention accelerates diabetic
      nephropathy.
AB  - Hyperlipidemia worsens diabetic nephropathy, although the mechanism by which
      renal lipids accumulate is unknown. We previously demonstrated that renal
      proteoglycans have high low-density lipoprotein (LDL) binding affinity,
      suggesting that proteoglycan-mediated LDL retention may contribute to renal lipid
      accumulation. The aim of this study was to determine the relative effect of
      diabetes and hyperlipidemia on renal proteoglycan content. Diabetic and non
      diabetic LDL receptor-deficient mice were fed diets containing 0% or 0.12%
      cholesterol for 26 weeks, and then kidneys were analyzed for renal lipid and
      proteoglycan content. Diabetic mice on the high-cholesterol diet had accelerated
      development of diabetic nephropathy with elevations in urine albumin excretion,
      glomerular and renal hypertrophy, and mesangial matrix expansion. Renal lipid
      accumulation was significantly increased by consumption of the 0.12% cholesterol
      diet, diabetes, and especially by both. The renal proteoglycans biglycan and
      decorin were detectable in glomeruli, with a significant increase in renal
      biglycan content in diabetic mice on the high-cholesterol diet. Renal biglycan
      and renal apolipoprotein B were colocalized, and regression analyses showed a
      significant relation between renal biglycan and renal apolipoprotein B content.
      The increased renal biglycan content in diabetic nephropathy probably contributes
      to renal lipid accumulation and the development of diabetic nephropathy.

PMID- 21723248
TI  - Supramolecular organization of photosystem II in green plants.
AB  - Green plant photosystem II (PSII) is involved in the light reactions of
      photosynthesis, which take place in the thylakoid membrane of the chloroplast.
      PSII is organized into large supercomplexes with variable amounts of membrane
      bound peripheral antenna complexes. These supercomplexes are dimeric and contain
      usually 2-4 copies of trimeric LHCII complexes and have a further tendency to
      associate into megacomplexes or into crystalline domains, of which several types
      have been characterized. This review focuses on the overall composition and
      structure of the PSII supercomplex of green plants and its organization and
      interactions within the photosynthetic membrane. Further, we present the current
      knowledge how the thylakoid membrane is three-dimensionally organized within the
      chloroplast. We also discuss how the supramolecular organization in the thylakoid
      membrane and the PSII flexibility may play roles in various short-term regulatory
      mechanisms of green plant photosynthesis. This article is part of a Special Issue
      entitled: Photosystem II.

PMID- 21723249
TI  - Structure and membrane orientation of IAPP in its natively amidated form at
      physiological pH in a membrane environment.
AB  - Human islet amyloid polypeptide is a hormone coexpressed with insulin by
      pancreatic beta-cells. For reasons not clearly understood, hIAPP aggregates in
      type II diabetics to form oligomers that interfere with beta-cell function,
      eventually leading to the loss of insulin production. The cellular membrane
      catalyzes the formation of amyloid deposits and is a target of amyloid toxicity
      through disruption of the membrane's structural integrity. Therefore, there is
      considerable current interest in solving the 3D structure of this peptide in a
      membrane environment. NMR experiments could not be directly utilized in lipid
      bilayers due to the rapid aggregation of the peptide. To overcome this
      difficulty, we have solved the structure of the naturally occurring peptide in
      detergent micelles at a neutral pH. The structure has an overall kinked helix
      motif, with residues 7-17 and 21-28 in a helical conformation, and with a 3(10)
      helix from Gly 33-Asn 35. In addition, the angle between the N- and C-terminal
      helices is constrained to 85 degrees . The greater helical content of human IAPP
      in the amidated versus free acid form is likely to play a role in its aggregation
      and membrane disruptive activity.

PMID- 21723250
TI  - Proinsulin maturation disorder is a contributor to the defect of subsequent
      conversion to insulin in beta-cells.
AB  - Disproportionate hyperproinsulinemia is an indicator of beta-cell dysfunction in
      diabetes and the basis underlying this abnormality remains obscure. Recently, we
      have found proinsulin is an aggregation-prone molecule inherent with a low
      relative folding rate and maintains a homeostatic balance of natively and
      plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) in
      normal beta-cells as a result of the integration of maturation and disposal
      processes. PIHO is susceptible to environmental and genetic influences.
      Perturbation of PIHO produces a number of toxic consequences with known
      association to beta-cell failure in diabetes. To explore whether the perturbation
      of PIHO has a link to disproportionate hyperproinsulinemia, we investigated
      proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2
      (PC2) in mouse Ins2(+/Akita) islets/beta-cells that preserve a primary PIHO
      disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene. Our metabolic
      labeling studies found an increased ratio of proinsulin to insulin in the
      cellular or released proteins of Ins2(+/Akita) islets. Histological, metabolic
      labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2
      immunoreactivities in the beta-cells of Ins2(+/Akita) islets in spite of no
      declines of these two convertases at the transcriptional and translational
      levels. Immunoblot analyses in cloned Ins2(+/Akita) beta-cells further confirmed
      the increased ratio of proinsulin to insulin despite the levels of PC1/3 and PC2
      proteins were not reduced somehow. The findings demonstrate that the perturbation
      of PIHO results in defects in the subsequent conversion process of proinsulin and
      is a contributor to the occurrence of disproportionate hyperproinsulinemia in
      diabetes.

PMID- 21723251
TI  - GSK-3beta inhibitors suppressed neuroinflammation in rat cortex by activating
      autophagy in ischemic brain injury.
AB  - Previous studies have shown that GSK-3beta inhibitor could reduce infarct volume
      after ischemia brain injury. However, the underlying mechanisms of GSK-3beta
      inhibitor involving neuroprotection remain poorly understood. In the present
      study, we demonstrated that GSK-3beta inhibitor suppressed insult-induced
      neuroinflammation in rat cortex by increasing autophagy activation in ischemic
      injury. Male rats were subjected to pMCAO (permanent middle cerebral artery
      occlusion) followed by treating with SB216763, a GSK-3beta inhibitor. We found
      that insult-induced inflammatory response was significantly decreased by
      intraperitoneal infusion of SB216763 in rat cortex. A higher level of autophagy
      was also detected after SB216763 treatment. In the cultured primary microglia,
      SB216763 activated autophagy and suppressed inflammatory response. Importantly,
      inhibition of autophagy by Beclin1-siRNA increased inflammatory response in the
      SB216763-treated microglia. These data suggest that GSK-3beta inhibitor
      suppressed neuroinflammation by activating autophagy after ischemic brain injury,
      thus offering a new target for prevention of ischemic brain injury.

PMID- 21723252
TI  - The pattern of gene expression and gene dose profiles of 6-Mercaptopurine- and 6
      Thioguanine-resistant human leukemia cells.
AB  - Exposure of MOLT4 human T-cell leukemia cells to 6-Mercaptopurine (6-MP) and 6
      Thioguanine (6-TG) resulted in acquired resistance associated with attenuated
      expression of the genes encoding concentrative nucleoside transporter 3 (CNT3)
      and equilibrative nucleoside transporter 2 (ENT2). To identify other alterations
      at the RNA and DNA levels associated with 6-MP- and 6-TG resistance, we compared
      here the patterns of gene expression and DNA copy number profiles of resistant
      sublines to those of the parental wild-type cells. The mRNA levels for two
      nucleoside transporters were down-regulated in both of the thiopurine-resistant
      sublines. Moreover, both of these cell lines expressed genes encoding the enzymes
      of purine nucleotide composition and synthesis, including adenylate kinase 3-like
      1 and guanosine monophosphate synthetase at significantly lower levels than wild
      type cells. In addition, expression of the mRNA for a specialized DNA polymerase,
      human terminal transferase encoded by the terminal deoxynucleotidyl transferase
      (DNTT) gene, was 122- and 93-fold higher in 6-TG- and 6-MP-resistant cells,
      respectively. The varying responses to 6-MP- and 6-TG observed here may help
      identify novel cellular targets and modalities of resistance to thiopurines, as
      well as indicating new potential approaches to individualization therapy with
      these drugs.

PMID- 21723253
TI  - SERPINB13 is a novel RUNX1 target gene.
AB  - RUNX1 is a critical transcription factor during embryogenesis and neoplastic
      disease. To identify novel transcriptional targets of RUNX1 in the context of
      chromatin, we performed genome wide location analysis (ChIP-on-chip). Here we
      report that SERPINB13, a gene downregulated in head and neck cancers, is a novel
      RUNX1transcriptional target. RUNX1 binds the SERPINB13 promoter in chromatin to
      repress its transcription. Mutation of either RUNX1 binding site in the SERPINB13
      promoter increased the activity of the promoter. Finally, overexpression of RUNX1
      and concomitant decrease in SERPINB13 expression led to increased activity of
      cathepsin K, an enzyme inhibited by SERPINB13. These data demonstrate that RUNX1
      is an important regulator of SERPINB13 and cathepsin K activity.

PMID- 21723254
TI  - Molecular hydrogen inhibits lipopolysaccharide/interferon gamma-induced nitric
      oxide production through modulation of signal transduction in macrophages.
AB  - Molecular hydrogen has been reported to be effective for a variety of disorders
      and its effects have been ascribed to the reduction of oxidative stress. However,
      we have recently demonstrated that hydrogen inhibits type I allergy through
      modulating intracellular signal transduction. In the present study, we examined
      the hydrogen effects on lipopolysaccharide/interferon gamma LPS/IFNgamma-induced
      nitric oxide (NO) production in murine macrophage RAW264 cells. Treatment with
      hydrogen reduced LPS/IFNgamma-induced NO release, which was associated with a
      diminished induction of inducible isoform of nitric oxide synthase (iNOS).
      Hydrogen treatment inhibited LPS/IFNgamma-induced phosphorylation of apoptosis
      signal-regulating kinase 1 (ASK1) and its downstream signaling molecules, p38 MAP
      kinase and JNK, as well as IkappaBalpha, but did not affect activation of NADPH
      oxidase and production of reactive oxygen species (ROS). As ROS is an upstream
      activator of ASK1, inhibition of ASK1 by hydrogen without suppressing ROS implies
      that a potential target molecule of hydrogen should be located at the receptor or
      immediately downstream of it. These results suggested a role for molecular
      hydrogen as a signal modulator. Finally, oral intake of hydrogen-rich water
      alleviated anti-type II collagen antibody-induced arthritis in mice, a model for
      human rheumatoid arthritis. Taken together, our studies indicate that hydrogen
      inhibits LPS/IFNgamma-induced NO production through modulation of signal
      transduction in macrophages and ameliorates inflammatory arthritis in mice,
      providing the molecular basis for hydrogen effects on inflammation and a
      functional interaction between two gaseous signaling molecules, NO and molecular
      hydrogen.

PMID- 21723255
TI  - Ultrasound-mediated interferon beta gene transfection inhibits growth of
      malignant melanoma.
AB  - We investigated the effects of ultrasound-mediated transfection
      (sonotransfection) of interferon beta (IFN-beta) gene on melanoma (C32) both in
      vitro and in vivo. C32 cells were sonotransfected with IFN-beta in vitro.
      Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra
      tumor injection with IFN-beta genes mixed with microbubbles. Successful
      sonotransfection with IFN-beta gene in vitro was confirmed by ELISA, which
      resulted in C32 growth inhibition. In vivo, the growth ratio of tumors
      transfected with IFN-beta gene was significantly lower than the other
      experimental groups. These results may lead to a new method of treatment against
      melanoma and other hard-to-treat cancers.

PMID- 21723256
TI  - Wisp2/CCN5 up-regulated in the central nervous system of GM3-only mice
      facilitates neurite formation in Neuro2a cells via integrin-Akt signaling.
AB  - Wisp2/CCN5 belongs to CCN family proteins which are involved in cell
      proliferation, angiogenesis, tumorigenesis and wound healing. Although a number
      of studies on the roles of Wisp2/CCN5 in cancers have been reported, no study on
      the expression and function of Wisp2/CCN5 in the central nervous system has been
      reported. In this study, we focused on Wisp2/CCN5 that was up-regulated in
      nervous tissues in GM3-only mice. Over-expression of Wisp2/CCN5 enhanced neurite
      outgrowth potently after serum withdrawal with increased phosphorylation levels
      of Akt and ERKs. When cells were cultured with recombinant Wisp2/CCN5 proteins,
      more and longer neurites were formed than in the controls. Thus, we demonstrated
      for the first time that Wisp2/CCN5 facilitates neurite formation in a mouse
      neuroblastoma cell line, Neuro2a. Akt phosphorylation induced by recombinant
      Wisp2/CCN5 was suppressed after knockdown of integrin beta1. Moreover, Wisp2/CCN5
      over-expressing cells were resistant to apoptosis induced by H(2)O(2). These
      results suggested that secreted Wisp2/CCN5 induces Akt and ERK phosphorylation
      via integrins, and consequently facilitates neurite formation and conferred
      resistance to apoptosis. Up-regulation of Wisp2/CCN5 in GM3-only mice should be,
      therefore, a reaction to protect nervous tissues from neurodegeneration caused by
      ganglioside deficiency.

PMID- 21723257
TI  - Identification of a putative Crimean-Congo hemorrhagic fever virus entry factor.
AB  - Entry of enveloped viruses into cells is initiated by binding of their envelope
      glycoproteins (Envs) to cell surface-associated receptors. The Crimean-Congo
      hemorrhagic fever virus (CCHFV) has two Envs, Gn and Gc, with poorly understood
      role in binding to susceptible cells. We expressed codon optimized Gn and Gc, and
      identified independently folded soluble Env fragments, one of which (Gc residues
      180-300) bound CCHFV susceptible cells supposedly by interacting with a putative
      receptor. This receptor binding domain (RBD) was used to identify its interacting
      partner by coimmunoprecipitation and mass spectrometry. Thus we identified the
      human cell surface nucleolin as a putative CCHFV entry factor. Nucleolin was
      expressed on all susceptible cells tested but not on the surface of cells
      resistant to CCHFV infection. Further studies are needed to explore the nucleolin
      function as a plausible CCHFV receptor and the molecular mechanisms of the Gc
      nucleolin interactions. The identification of the CCHFV RBD and its binding
      partner could provide novel targets for therapy and tools for prevention as well
      as more complete understanding of the mechanisms of CCHFV entry and pathogenesis.

PMID- 21723258
TI  - Identification of epigenetically silenced genes in human pancreatic cancer by a
      novel method "microarray coupled with methyl-CpG targeted transcriptional
      activation" (MeTA-array).
AB  - Identification and characterization of epigenetically silenced genes is important
      for cancer research, because information from hypermethylated genes provides
      clues to understand roles of epigenetics in tumorigeneses and genes frequently
      methylated in a tumor-specific manner can be used as tumor markers. Here, we
      describe the identification of transcriptionally silenced hypermethylated genes
      in pancreatic cancer cells by using a novel method called "microarray coupled
      with methyl-CpG targeted transcriptional activation" (MeTA-array for short),
      which can effectively reactivate genes containing the stringent criteria of CpG
      islands at promoter regions. Three representative pancreatic cancer cell lines,
      AsPC-1, MIA PaCa-2 and PANC-1, with a normal pancreatic ductal epithelial cell
      line HPDE as a control, were examined with this method, and 19 genes were
      upregulated twofold or more in all the three cancer cell lines after MeTA; 16 of
      these 19 genes have not been detected previously when using a conventional DNA
      demethylating agent, 5-aza-2'-deoxycytidine. Among these 16 genes, CSMD2,
      SLC32A1, TMEM204 and TRH were further analyzed by methylation-specific PCR, and
      we found that 90% (19/21) of CSMD2, 100% (21/21) of SLC32A1, 95% (20/21) of
      TMEM204 and 100% (21/21) of TRH were methylated in our series of pancreatic
      cancer cell lines. Furthermore, CSMD2, SLC32A1 and TRH were also hypermethylated
      in primary pancreatic cancers in a tumor-specific manner. These results suggest
      that MeTA-array is a highly efficient method for identifying methylation-mediated
      transcriptionally silenced genes in human pancreatic cancer and that this method
      can be applied to other types of human cancer.

PMID- 21723259
TI  - The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA
      deletions in a patient with Wolfram syndrome and cardiomyopathy.
AB  - Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD
      (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a
      heterogeneous disease and full characterization of all clinical and biological
      features of this disorder is difficult. The wide spectrum of clinical expression,
      affecting several organs and tissues, and the similarity in phenotype between
      patients with Wolfram syndrome and those with certain types of respiratory chain
      diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome
      patients. We report a Tunisian patient with clinical features of moderate Wolfram
      syndrome including diabetes, dilated cardiomyopathy and neurological
      complications. The results showed the presence of the mitochondrial ND1 m.3337G>A
      mutation in almost homoplasmic form in 3 tested tissues of the proband (blood
      leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR
      amplifications revealed the presence of multiple deletions of the mitochondrial
      DNA extracted from the patient's skeletal muscle removing several tRNA and
      protein-coding genes. Our study reported a Tunisian patient with clinical
      features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we
      detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.

PMID- 21723260
TI  - Expression of galectin-9 by IFN-gamma stimulated human nasal polyp fibroblasts
      through MAPK, PI3K, and JAK/STAT signaling pathways.
AB  - Galectin-9 exhibited potent and selective eosinophil chemoattractant activity and
      attracted eosinophils in vitro and in vivo. Nasal polyposis is a chronic
      inflammatory disease of the upper airway characterized by the marked presence of
      inflammatory cells, particularly eosinophils. Thus, galectin-9 may be implicated
      in the pathogenesis of nasal polyposis. The study was designed to investigate
      whether interferon-gamma (IFN-gamma) can induce the augmentation of galectin-9
      expression and induce the expression of galectin-9 in nasal polyps. We examined
      the correlation between galectin-9 expression and eosinophil infiltration in
      nasal polyps. In addition, we identified the signaling pathways involved in the
      elevation of galectin-9 expression in response to IFN-gamma. Our data demonstrate
      that the involvement of mitogen-activated protein kinases (MAPKs),
      phosphatidylinositol 3 phosphate kinase (PI3K), and Janus kinase/signal
      transducer and activator of transcription (JAK/STAT) may play important roles in
      the selective recruitment of eosinophils in nasal polyp tissues through the
      production of galectin-9. These findings suggest that galectin-9 expression is
      associated with eosinophil infiltration in polyps of patients with nasal
      polyposis.

PMID- 21723261
TI  - Inhibition of melanogenesis by 5,7-dihydroxyflavone (chrysin) via blocking
      adenylyl cyclase activity.
AB  - Due to its multiple biological activities, 5,7-dihydroxyflavone (chrysin) in
      propolis has gained attention as potentially useful therapeutics for various
      diseases. However, the efficacy of chrysin for the use of dermatological health
      has not been fully explored. To clarify the action mechanism of the skin
      protecting property of chrysin, we firstly investigated the molecular docking
      property of chrysin on the mammalian adenylyl cyclase, which is the key enzyme of
      cAMP-induced melanogenesis. We also examined the involvement of chrysin in alpha
      MSH and forskolin-induced cAMP signaling within a cell based assay. In addition,
      we inquired into the inhibitory effect of chrysin on melanogenesis and found that
      the pretreatment with chrysin inhibited the forskolin-induced melanin contents
      significantly without annihilating the cell viability. These results strongly
      suggest that chrysin directly inhibits the activity of adenylyl cyclase,
      downregulates forskolin-induced cAMP-production pathway, consequently inhibiting
      melanogenesis. Thus, chrysin may also be used as an effective inhibitor of
      hyperpigmentation.

PMID- 21723262
TI  - The reduced trabecular bone mass of adult ARKO male mice results from the
      decreased osteogenic differentiation of bone marrow stroma cells.
AB  - Male mice with androgen receptor knock-out (ARKO) show significant bone loss at a
      young age. However, the lasting effect of AR inactivation on bone in aging male
      mice remains unclear. We designed this study to evaluate the effect of AR on bone
      quality in aging male mice and to find the possible causes of AR inactivation
      contributing to the bone loss. The mice were grouped according to their ages and
      AR status and their trabecular bones were examined by micro-CT analysis at 6, 12,
      18, and 30 weeks old. We found that bone mass consistently decreased and the bone
      microarchitectures continuously deteriorated in male ARKO mice at designated time
      points. To determine the cause of the bone loss in ARKO mice, we further examined
      the role of AR in bone cell fate decision and differentiation and we conducted
      experiments on bone marrow stromal cells (BMSC) obtained from wild type (WT) and
      AR knockout (KO) mice. We found that ARKO mice had higher numbers of colony
      formation unit-fibroblast (CFU-F), and CD44 and CD34 positive cells in bone
      marrow than WT mice. Our Q-RT-PCR results showed lower expression of genes linked
      to osteogenesis in BMSCs isolated from ARKO mice. In conclusion, AR nullification
      disrupted bone microarchitecture and caused trabecular bone mass loss in male
      ARKO mice. And the fate of BMSCs was impacted by the loss of AR. Therefore, these
      findings suggest that AR may accelerate the use of progenitor cells and direct
      them into osteogenic differentiation to affect bone metabolism.

PMID- 21723263
TI  - A new function of Nell-1 protein in repressing adipogenic differentiation.
AB  - A theoretical inverse relationship has long been postulated for osteogenic and
      adipogenic differentiation (bone versus adipose tissue differentiation). This
      inverse relationship in theory at least partially underlies the clinical entity
      of osteoporosis, in which marrow mesenchymal stem cells (MSCs) have a
      predilection for adipose differentiation that increases with age. In the present
      study, we assayed the potential anti-adipogenic effects of Nell-1 protein (an
      osteoinductive molecule). Using 3T3-L1 (a human preadipocyte cell line) cells and
      human adipose-derived stromal cells (ASCs), we observed that adenoviral delivered
      (Ad)-Nell-1 or recombinant NELL-1 protein significantly reduced adipose
      differentiation across all markers examined (Oil red O staining, adipogenic gene
      expression [Pparg, Lpl, Ap2]). In a prospective fashion, Hedgehog signaling was
      assayed as potentially downstream of Nell-1 signaling in regulating osteogenic
      over adipogenic differentiation. In comparison to Ad-LacZ control, Ad-Nell-1
      increased expression of hedgehog signaling markers (Ihh, Gli1, Ptc1). These
      studies suggest that Nell-1 is a potent anti-adipogenic agent. Moreover, Nell-1
      signaling may inhibit adipogenic differentiation via a Hedgehog dependent
      mechanism.

PMID- 21723264
TI  - Decorin gene expression and its regulation in human keratinocytes.
AB  - In various cell types, including cancer cells, decorin is involved in regulation
      of cell attachment, migration and proliferation. In skin, decorin is seen in
      dermis, but not in keratinocytes. We show that decorin gene (DCN) is expressed in
      the cultured keratinocytes, and the protein is found in the cytoplasm of
      differentiating keratinocytes and in suprabasal layers of human epidermis. RT-PCR
      experiments showed that DCN expression is regulated by pro-inflammatory and
      proliferative cytokines. Our data suggest that decorin should play a significant
      role in keratinocyte terminal differentiation, cutaneous homeostasis and
      dermatological diseases.

PMID- 21723265
TI  - Functional characterisation of Lp_2714, an EAL-domain protein from Lactobacillus
      plantarum.
AB  - Bioinformatic analysis of lp_2714 from Lactobacillus plantarum WCFS1 demonstrates
      that it encodes an EAL-domain protein associated with a membrane targeting signal
      sequence. Comparison of the predicted primary amino-acid sequence of Lp_2714
      shows that it lacks critical catalytic residues and heterologous expression has
      determined that it does not encode a functional phosphodiesterase. We designate
      Lp_2714 as a class-3 EAL domain protein probably involved in regulating
      polysaccharide synthesis on the cell surface the cell.

PMID- 21723266
TI  - Plasmalogens the neglected regulatory and scavenging lipid species.
AB  - Plasmalogens are a class of phospholipids carrying a vinyl ether bond in sn-1 and
      an ester bond in sn-2 position of the glycerol backbone. Although they are
      widespread in all tissues and represent up to 18% of the total phospholipid mass
      in humans, their physiological function is still poorly understood. The aim of
      this review is to give an overview over the current knowledge in plasmalogen
      biology and pathology with an emphasis on neglected aspects of their involvement
      in neurological and metabolic diseases. Furthermore a better understanding of
      plasmalogen biology in health and disease could also lead to the development of
      better diagnostic and prognostic biomarkers for vascular and metabolic diseases
      such as obesity and diabetes mellitus, inflammation, neuro-degeneration and
      cancer.

PMID- 21723267
TI  - The thermotropism and prototropism of ternary mixtures of ceramide C16,
      cholesterol and palmitic acid. An exploratory study.
AB  - Mixtures of ceramides with other lipids in the presence of water are key
      components of the structure of the lipid matrix of the stratum corneum and are
      involved in lateral phase separation processes occurring in lipid membranes.
      Besides their structural role, ceramides are functional for cell signaling and
      trafficking. We elected, as our object of study, a mixture of N
      hexadecanoylceroyl-d-erythro-sphyngosine, C16-Cer, with cholesterol, Ch, in a
      molar proportion 54:46 in excess water to which palmitic acid, PA, is added in
      varying amounts. The chosen C16-Cer:Ch proportion replicates the relative
      abundance of ceramides and cholesterol found in the stratum corneum lipid matrix.
      For each lipidic composition, we identify the phases in equilibrium and study the
      thermotropism of the system, using differential scanning calorimetry and
      temperature-dependent small and wide-angle X-ray powder diffraction. Since the
      molecular aggregation of the system and its mesoscopic properties are affected by
      the degree of protonation of the PA, we explore mixtures with several PA contents
      at two extreme pH values, 9.0 and 4.0. A specific C16-Cer:Ch:PA composition forms
      at pH 9.0 a lamellar crystalline aggregate, to which we attribute the
      stoichiometry C16-Cer(5)Ch(4)PA(2), that melts at 88-90  degrees C to give a
      H(II) phase. For pH values at which there is partial or total protonation of PA
      another L(C) C16-Cer:Ch (2:3) stoichiometric aggregate is observed, identical to
      that previously reported for C16-Cer:Ch mixtures (Souza et al., 2009, J. Phys.
      Chem. B, 113, 1367-1375), coexisting with a lamellar fluid phase. For pH 4.0 and
      7.0, the existing lamellar liquid crystalline converts into a isotropic fluid
      phase at high temperatures. It is also found that the miscibility of PA in the
      C16-Cer:Ch mixture at pH 4.0 does not exceed ca. 18 mol%, but for pH 9.0 no free
      PA is detected at least until 60 mol%.

PMID- 21723268
TI  - Synergistic cosolubilization of omega-3 fatty acid esters and CoQ10 in dilutable
      microemulsions.
AB  - Water-dilutable microemulsions were prepared and loaded with two types of omega-3
      fatty acid esters (omega-3 ethyl esters, OEE; and omega-3 triacylglycerides,
      OTG), each separately and together with ubiquinone (CoQ(10)). The microemulsions
      showed high and synergistic loading capabilities. The linear fatty acid ester
      (OEE) solubilization capacity was greater than that of the bulky and robust OTG.
      The location of the guest molecules within the microemulsions at any dilution
      point were determined by electrical conductivity, viscosity, DSC, SAXS, cryo-TEM,
      SD-NMR, and DLS. We found that OEE molecules pack well within the surfactant
      tails to form reverse micelles that gradually, upon water dilution, invert into
      bicontinuous phase and finally into O/W droplets. The CoQ(10) increases the
      stabilization and solubilization of the omega-3 fatty acid esters because it
      functions as a kosmotropic agent in the micellar system. The hydrophobic and
      bulky OTG molecule strongly interferes with the tail packing and spaces them
      significantly - mainly in the low and medium range water dilutions. When added to
      the micellar system, CoQ(10) forms some reverse hexagonal mesophases. The
      inversion into direct micelles is more difficult in comparison to the OEE system
      and requires additional water dilution. The OTG with or without CoQ(10)
      destabilizes the structures and decreases the solubilization capacity since it
      acts as a chaotropic agent to the micellar system and as a kosmotropic agent to
      hexagonal packing. These results explain the differences in the behavior of these
      molecules with vehicles that solubilize them in aqueous phases. Temperature
      disorders the bicontinuous structures and reduces the supersaturation of the
      system containing OEE with CoQ(10); as a result CoQ(10) crystallization is
      retarded.

PMID- 21723269
TI  - Genetic profiling of GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in an
      Argentinian population.
AB  - OBJECTIVES: To determine the frequencies of relevant allelic variants in oncology
      for the GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in a population from Central
      Argentina. To compare the allelic distribution found with the frequencies
      reported for other ethnic groups. DESIGN AND METHODS: Genotyping was carried out
      in a total of 102 unrelated Argentinian subjects. FCGR3A (rs396991) was detected
      using allele specific polymerase chain reaction (PCR) assay, while GSTP1
      (rs1695), DPYD (rs3918290), FCGR2A (rs1801274) and CCND1 (rs9344) variants were
      assessed by PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The
      allele frequencies for GSTP*1B, DPYD*2A, FCGR2A (131R), FCGR3A (158F) and CCND1
      (870G) in Argentinians were 0.35, 0.005, 0.41, 0.77 and 0.47, respectively.
      CONCLUSIONS: We found that the Argentinian population tested resembles other
      Caucasians populations, especially Spaniards; yet the differences in allele
      distribution with other Caucasian groups, uncover population admixture with
      native Amerindian and other ethnic groups, consistent with the well documented
      immigration flows landing Argentina from several countries.

PMID- 21723270
TI  - Study of serum antioxidant capacity and relation with CA 19-9 and PSA in patients
      with gastrointestinal tract and prostate tumors.
AB  - OBJECTIVES: We undertook the present study to investigate the possible relation
      between total antioxidant capacity (TAC) and tumor marker (TM) values in serum
      samples of patients with and without gastrointestinal tract and prostate tumors.
      DESIGN AND METHODS: We measured the TAC using trolox equivalent antioxidant
      capacity (TEAC) and oxygen radical absorption capacity (ORAC) assays in 80 serum
      samples: 20 presented elevated values of CA 19-9; 20 had elevated PSA levels and
      two groups of 20 samples had values within reference ranges respectively.
      RESULTS: Total antioxidant capacity - measured using the two different analytical
      methods - was higher in serum samples from patients with elevated CA 19-9 and PSA
      levels. This antioxidant status, measured by ORAC assay, correlated significantly
      with CA 19-9 (r: 0.502, P<0.05) and PSA (r:0.792, P<0.001) when the values of
      these tumor markers were pathological. CONCLUSIONS: We concluded that increased
      serum TAC of the patients with altered levels of CA 19-9 and PSA may be due to
      the response of increased reactive oxygen species and can be considered as a sign
      of oxidative stress of these patients. We know that tumor markers are a useful
      tool for follow-up care of oncologic patients, whereas their role in the
      diagnosis of a malignancy is controversial. Therefore, the evaluation of serum
      antioxidant capacity in these pathological processes could contribute to improve
      diagnosis of these patients.

PMID- 21723271
TI  - Risk stratification and clinical outcomes in patients with acute pulmonary
      embolism.
AB  - OBJECTIVES: Pulmonary embolism is a common disease associated with a high
      mortality rate. The risk assessment and appropriate treatment selection of
      patients with acute pulmonary embolism remains a challenge. DESIGN AND METHODS:
      This single center cohort study included a total of 150 patients (96 male, age =
      71 +/- 15 years) with acute pulmonary embolism confirmed by spiral-computed
      tomography or magnetic resonance image. The prognostic performance of the
      clinical characteristics and laboratory values were investigated to predict the
      in-hospital hemodynamically instable events and 30-day all-cause mortality.
      RESULTS: The rate of in-hospital hemodynamic instability and 30-day all-cause
      mortality was 21% and 12%, respectively. A multivariate Cox regression analysis
      demonstrated that a heart rate >= 110 bpm (odd ratio 4.26 [95% CI 1.42-12.77]),
      chronic pulmonary disease (6.47 [1.99-21.04]), WBC >= 11,000 mm(3) (3.78 [1.32
      10.82]), and D-dimer level >= 4.0 MUg/mL (3.68 [1.01-13.43]) independently
      predicted the 30-day fatal outcome. A Kaplan-Meier survival analysis showed that
      the categorization based on the number of risk factors was significantly
      associated with the likelihood of 30-day all-cause mortality (P<0.0001).
      CONCLUSIONS: The initial presentation of tachycardia, presence of chronic
      pulmonary disease, elevated WBC and D-dimer on admission can be used to identify
      the risk for a short-term fatal outcome within 30 days in patients with acute
      pulmonary embolism.

PMID- 21723272
TI  - A sensitive method to quantify human cell-free circulating DNA in blood:
      relevance to myocardial infarction screening.
AB  - OBJECTIVES: Human cell-free circulating DNA (cf-DNA) derived mainly from cell
      apoptosis and necrosis can be measured by a variety of laboratory techniques, but
      almost all of these methods require sample preparation. We have developed a
      branched DNA (bDNA)-based Alu assay for quantifying cf-DNA in myocardial
      infarction (MI) patients. DESIGN AND METHODS: A total of 82 individuals were
      included in the study; 22 MI and 60 normal controls. cf-DNA was quantified using
      a bDNA-based Alu assay. RESULTS: cf-DNA was higher in serum compared to plasma
      and there was a difference between genders. cf-DNA was significantly higher in MI
      patients compared to the controls. There was no correlation between cf-DNA and
      creatine kinase-MB (CK-MB), troponin I (cTnI) or myoglobin (MYO). In serial
      specimens, cf-DNA was sensitive and peaked earlier than cTnI. CONCLUSIONS: The
      bDNA-based Alu assay is a novel method for quantifying human cf-DNA. Increased cf
      DNA in MI patients might complement cTnI, CK-MB and MYO in a multiple marker
      format.

PMID- 21723273
TI  - Precise cis-regulatory control of spatial and temporal expression of the alx-1
      gene in the skeletogenic lineage of s. purpuratus.
AB  - Deployment of the gene-regulatory network (GRN) responsible for skeletogenesis in
      the embryo of the sea urchin Strongylocentrotus purpuratus is restricted to the
      large micromere lineage by a double negative regulatory gate. The gate consists
      of a GRN subcircuit composed of the pmar1 and hesC genes, which encode repressors
      and are wired in tandem, plus a set of target regulatory genes under hesC
      control. The skeletogenic cell state is specified initially by micromere-specific
      expression of these regulatory genes, viz. alx1, ets1, tbrain and tel, plus the
      gene encoding the Notch ligand Delta. Here we use a recently developed high
      throughput methodology for experimental cis-regulatory analysis to elucidate the
      genomic regulatory system controlling alx1 expression in time and embryonic
      space. The results entirely confirm the double negative gate control system at
      the cis-regulatory level, including definition of the functional HesC target
      sites, and add the crucial new information that the drivers of alx1 expression
      are initially Ets1, and then Alx1 itself plus Ets1. Cis-regulatory analysis
      demonstrates that these inputs quantitatively account for the magnitude of alx1
      expression. Furthermore, the Alx1 gene product not only performs an auto
      regulatory role, promoting a fast rise in alx1 expression, but also, when at high
      levels, it behaves as an auto-repressor. A synthetic experiment indicates that
      this behavior is probably due to dimerization. In summary, the results we report
      provide the sequence level basis for control of alx1 spatial expression by the
      double negative gate GRN architecture, and explain the rising, then falling
      temporal expression profile of the alx1 gene in terms of its auto-regulatory
      genetic wiring.

PMID- 21723275
TI  - Bi-polarized translation of ascidian maternal mRNA determinant pem-1 associated
      with regulators of the translation machinery on cortical Endoplasmic Reticulum
      (cER).
AB  - Polarized cortical mRNA determinants such as maternal macho-1 and pem-1 in
      ascidians, like budding yeast mating factor ASH1 reside on the cER-mRNA domain a
      subdomain of cortical Endoplasmic Reticulum(ER) and are translated in its
      vicinity. Using high resolution imaging and isolated cortical fragments prepared
      from eggs and embryos we now find that macho-1 and pem-1 RNAs co-localize with
      phospho-protein regulators of translation initiation (MnK/4EBP/S6K). Translation
      of cortical pem-1 RNA follows its bi-polarized relocalization. About 10 min after
      fertilization or artificial activation with a calcium ionophore, PEM1 protein is
      detected in the vegetal cortex in the vicinity of pem-1 RNA. About 40 min after
      fertilization-when pem-1 RNA and P-MnK move to the posterior pole-PEM1 protein
      remains in place forming a network of cortical patches anchored at the level of
      the zygote plasma membrane before disappearing. Cortical PEM1 protein is detected
      again at the 4 cell stage in the posterior centrosome attracting body (CAB)
      region where the cER-mRNA domain harboring pem-1/P-MnK/P-4EBP/P-S6K is
      concentrated. Bi-polarized PEM1 protein signals are not detected when pem-1
      morpholinos are injected into eggs or zygotes or when MnK is inhibited. We
      propose that localized translation of the pem-1 RNA determinant is triggered by
      the fertilization/calcium wave and that the process is controlled by phospho
      protein regulators of translation initiation co-localized with the RNA
      determinant on a sub-domain of the cortical Endoplasmic Reticulum.

PMID- 21723274
TI  - Identification of an evolutionarily conserved regulatory element of the zebrafish
      col2a1a gene.
AB  - Zebrafish (Danio rerio) is an excellent model organism for the study of
      vertebrate development including skeletogenesis. Studies of mammalian cartilage
      formation were greatly advanced through the use of a cartilage specific
      regulatory element of the Collagen type II alpha 1 (Col2a1) gene. In an effort to
      isolate such an element in zebrafish, we compared the expression of two col2a1
      homologues and found that expression of col2a1b, a previously uncharacterized
      zebrafish homologue, only partially overlaps with col2a1a. We focused our
      analysis on col2a1a, as it is expressed in both the stacked chondrocytes and the
      perichondrium. By comparing the genomic sequence surrounding the predicted
      transcriptional start site of col2a1a among several species of teleosts we
      identified a small highly conserved sequence (R2) located 1.7 kb upstream of the
      presumptive transcriptional initiation site. Interestingly, neither the sequence
      nor location of this element is conserved between teleost and mammalian Col2a1.
      We generated transient and stable transgenic lines with just the R2 element or
      the entire 1.7 kb fragment 5' of the transcriptional initiation site. The
      identified regulatory elements enable the tracking of cellular development in
      various tissues by driving robust reporter expression in craniofacial cartilage,
      ear, notochord, floor plate, hypochord and fins in a pattern similar to the
      expression of endogenous col2a1a. Using a reporter gene driven by the R2
      regulatory element, we analyzed the morphogenesis of the notochord sheath cells
      as they withdraw from the stack of initially uniform cells and encase the
      inflating vacuolated notochord cells. Finally, we show that like endogenous
      col2a1a, craniofacial expression of these reporter constructs depends on Sox9a
      transcription factor activity. At the same time, notochord expression is
      maintained after Sox9a knockdown, suggesting that other factors can activate
      expression through the identified regulatory element in this tissue.

PMID- 21723276
TI  - 5-HT(1A) receptor sensitivity in 5-HT(1B) receptor KO mice is unaffected by
      chronic fluvoxamine treatment.
AB  - The 5-HT(1B) receptor has been implicated in disorders such as depression,
      anxiety and obsessive-compulsive disorder. In mice lacking the 5-HT(1B) receptor
      (5-HT(1B) knockout mice), important changes in physiology and behavior exist. In
      the absence of presynaptic 5-HT(1B) receptor inhibition, chronic SSRI treatment
      may differentially affect 5-HT(1A) receptor functionality. The present studies
      tested the hypothesis that chronically reducing 5-HT transporter (5-HTT) function
      with selective serotonin reuptake inhibitor (SSRI) treatment would accelerate 5
      HT(1A) receptor desensitization in 5-HT(1B) knockout mice. Moreover, as 5-HT(1B)
      knockout mice have been found to display exaggerated autonomic and locomotor
      responses to environmental stressors, the effects of chronic SSRI treatment on
      the hyperreactive phenotype of 5-HT(1B) knockout mice were investigated. The
      stress-reducing effect of the 5-HT(1A) receptor agonist flesinoxan on increases
      in body temperature, heart rate and locomotor activity was similar in wild type
      and 5-HT(1B) knockout mice before and after chronic 21-day treatment with the
      SSRI fluvoxamine, indicating no apparent alteration of 5-HT(1A) receptor
      sensitivity in 5-HT(1B) knockout mice. Also, chronic SSRI treatment did not alter
      the increased stress reactivity to mild environmental stressors in 5-HT(1B)
      knockout mice. We demonstrate that no apparent differences in 5-HT(1A) receptor
      sensitivity occur between 5-HT(1B) knockout and wild type mice after chronic
      fluvoxamine treatment. Also, the hyperreactive phenotype of 5-HT(1B) knockout
      mice is unresponsive to chronic SSRI treatment. Taken together, these results
      indicate that constitutive absence of 5-HT(1B) receptors does not result in
      adaptive changes in 5-HT(1A) receptor functionality and that chronic SSRI
      treatment does not modify stress reactivity in 5-HT(1B) knockout mice.

PMID- 21723277
TI  - Luteolin improves contractile function and attenuates apoptosis following
      ischemia-reperfusion in adult rat cardiomyocytes.
AB  - Luteolin occurs in a variety of plants and possesses antioxidant and anti
      inflammatory properties. However, its role in protection against ischemia
      reperfusion injury in Sprague-Dawley rats has not been elucidated. In the present
      study, we tested the contractile function of left ventricular cardiomyocytes with
      different concentrations of luteolin: 0.5, 1.5, 2.5 and 5.0 MUg/ml after
      simulated. We investigated the direct effect of luteolin against necrosis and
      apoptosis following ischemia-reperfusion in cardiomyocytes. We further observed
      the function of isolated hearts subjected to ischemia-reperfusion with or without
      10.0 MUg/ml luteolin pretreatment. Following 24h incubation with or without
      luteolin, adult rat cardiomyocytes were subjected to 3h of ischemia followed by
      2h of reperfusion for contractile function and necrosis (trypan blue exclusion
      and lactate dehydrogenase release) or 18 h of reperfusion for apoptosis studies.
      The cardiomyocyte shortening amplitude depended on different concentrations of
      luteolin, increasing significantly at 2.5 MUg/ml luteolin (P<0.01). Necrosis and
      apoptosis were reduced by luteolin at 2.5 MUg/ml. In addition, the expression of
      Bcl-2 was upregulated by luteolin and the ratio of Bax to Bcl-2 was decreased.
      Luteolin inhibited the activation of Caspase3 after ischemia-reperfusion in
      cardiomyocytes. Furthermore, luteolin at 10.0 MUg/ml improved ischemia
      reperfusion induced myocardial function, by improving heart rate, +dp/dt(max) and
      -dp/dt(max), and also limiting the decline of left ventricular systolic pressure
      (LVSP) and elevation of left ventricular end-diastolic pressure (LVEDP) to some
      extent. Our results demonstrated that luteolin prevents ischemia-reperfusion
      injury by reducing necrosis and apoptosis in rat cardiomyocytes.

PMID- 21723278
TI  - Angiopoietins-1 and -2 play opposing roles in endothelial sprouting of embryoid
      bodies in 3D culture and their receptor Tie-2 associates with the cell-cell
      adhesion molecule PECAM1.
AB  - Angiopoietins 1 and 2, ligands for the receptor kinase Tie-2, have been proposed
      to play critical but opposing roles in vascular development. Since signaling by
      Tie-2 is likely affected by other endothelial cell receptors such as Flk-1, the
      receptor for VEGF, and cell-cell adhesion receptors PECAM1 and VE-cad, we
      explored their interactions in a 3D model of vasculogenesis. When murine embryoid
      bodies (EBs) were treated with VEGF in Matrigel in the presence or absence of Ang
      1 or Ang-2 for eight days, Ang-1 abrogated vascular sprouting for treatments
      started at days 0 or 3. In contrast, Ang-2 greatly accelerated vascular sprouting
      compared to untreated EBs. These results were confirmed in a second model system
      where VEGF treated HUVECs were grown in Matrigel in the presence or absence of
      Ang-1 or Ang-2. Since vascular sprouting must be precisely controlled in the
      developing embryo, it is likely that cell-cell adhesion molecules play a role in
      sensing the density of vascular sprouts. In this respect, we have shown that
      PECAM1 and CEACAM1 play essential roles in vascular sprouting. We now show that
      PECAM1 is associated with Tie-2, becomes phosphorylated on its ITIMs, and
      recruits the inhibitory phosphatases SHP-1 and SHP-2. In addition, PECAM1 is
      associated with VE-cad and may similarly regulate its signaling via recruitment
      of SHP-1/2.

PMID- 21723279
TI  - BAG-1L promotes keratinocyte differentiation in organotypic culture models and
      changes in relative BAG-1 isoform abundance may lead to defective stratification.
AB  - In keratinocytes the human Bag-1 gene produces three different protein isoforms
      from a single messenger RNA, BAG-1L, BAG-1M and BAG-1S. In this study we
      questioned whether BAG-1L or the shorter isoforms would promote keratinocyte
      differentiation in organotypic cultures of HaCaT. HaCaT parental and vector cells
      showed stratification, but terminal differentiation was not complete. Cultures
      overexpressing BAG-1L isoform-specifically were of increased thickness,
      demonstrated pronounced expression of basal cytokeratin 5 and beta1-integrin,
      suprabasal involucrin, cytokeratin 1 and plasma membrane-localised filaggrin, and
      a marked keratinized layer of cells at the surface. We were unable to overexpress
      BAG-1S and BAG-1M isoform-specifically. Overexpression of BAG-1M gave rise to
      organotypic cultures intermediate in differentiation to controls and those
      overexpressing BAG-1L. Cells overexpressing BAG-1S also exhibited elevated
      endogenous BAG-1. These produced slow growing cultures with high levels of basal
      cytokeratin 5, but little involucrin or cytokeratin 1. Suprabasal beta1-integrin
      and Ki67 positive cells indicated defective stratification. The results suggest
      that BAG-1L potentiates epidermal differentiation, but disruption in the relative
      balance of isoforms towards overexpression of BAG-1S can lead to defective tissue
      patterning. Hence, a delicate balance of BAG-1 isoforms may be required to
      regulate normal epidermal stratification and differentiation, with important
      implications for aberrant differentiation in cancer.

PMID- 21723281
TI  - Methods being developed for preparation, delivery and transplantation of a tissue
      engineered corneal endothelium.
AB  - Corneal transplantation is the only available treatment to restore vision in
      patients suffering from endotheliopathies. Tissue engineering offers new
      alternatives for the replacement of dysfunctional corneal endothelial cells. This
      review reports the current knowledge on the reconstruction and transplantation of
      a tissue-engineered corneal endothelium. It describes the cell source, cell
      isolation, culture, carriers used for reconstruction, as well as alternatives to
      using carriers. It also reviews the different in vitro and in vivo assessments
      used to characterize the tissue-engineered endothelium and the different animal
      models used to test its functionality. Finally, a brief discussion describes the
      steps and requirements for the technological transfer from bench to bedside.

PMID- 21723280
TI  - Retinal proliferation response in the buphthalmic zebrafish, bugeye.
AB  - The zebrafish retina regenerates in response to acute retinal lesions, replacing
      damaged neurons with new neurons. In this study we test the hypothesis that
      chronic stress to inner retinal neurons also triggers a retinal regeneration
      response in the bugeye zebrafish. Mutations in the lrp2 gene in zebrafish are
      associated with a progressive eye phenotype (bugeye) that models several risk
      factors for human glaucoma including buphthalmos (enlarged eyes), elevated
      intraocular pressure (IOP), and upregulation of genes related to retinal ganglion
      cell pathology. The retinas of adult bugeye zebrafish showed high rates of
      ongoing proliferation which resulted in the production of a small number of new
      retinal neurons, particularly photoreceptors. A marker of mechanical cell stress,
      Hsp27, was strongly expressed in inner retinal neurons and glia of bugeye
      retinas. The more enlarged eyes of individual bugeye zebrafish showed disrupted
      retinal lamination, and a persistent reduced density of neurons in the ganglion
      cell layer (GCL), although total numbers of GCL neurons were higher than in
      control eyes. Despite the presence of a proliferative response to damage, the
      adult bugeye zebrafish remained behaviorally blind. These findings suggest the
      existence of an unsuccessful regenerative response to a persistent pathological
      condition in the bugeye zebrafish.

PMID- 21723282
TI  - Strongyloides ratti infection modulates B and T cell responses to third party
      antigens.
AB  - It is estimated that over one third of the world population is infected with
      helminths, Strongyloides ssp. accounting for approximately 30-100 million cases.
      As helminth infections often result in a modulation of the host's immune system,
      infected people may display impaired responses to concurrent infections and to
      third party antigens. Here, we employ the experimental system of murine
      Strongyloides ratti infection to investigate the impact of helminth infections on
      experimental vaccinations. We demonstrate that concurrent infection with S. ratti
      strongly affected the humoral response to a thymus dependent model antigen,
      whereby predominantly Th1 associated IgG2b production was suppressed. We provide
      evidence that this suppression was due to modulation of T helper cell and not B
      cell function as the responses to a thymus independent model antigen remained
      unchanged in S. ratti infected mice. Moreover, using an adoptive transfer system,
      we show that infection with S. ratti directly interfered with antigen-specific
      proliferation of T cell receptor transgenic CD4(+) T helper cells in vivo.
      Finally, using IL-10 deficient mice and mice that selectively lack T helper cell
      derived IL-10 we rule out a role for host-derived IL-10 in mediating the
      suppression of thymus dependent model antigen response in S. ratti infected mice.

PMID- 21723283
TI  - Epigenetic regulation of microRNA-375 and its role in melanoma development in
      humans.
AB  - To identify epigenetically regulated miRNAs in melanoma, we treated a stage 3
      melanoma cell line WM1552C, with 5AzadC and/or 4-PBA. Several hypermethylated
      miRNAs were detected, one of which, miR-375, was highly methylated and was
      studied further. Minimal CpG island methylation was observed in melanocytes,
      keratinocytes, normal skin, and nevus but hypermethylation was observed in
      patient tissue samples from primary, regional, distant, and nodular metastatic
      melanoma. Ectopic expression of miR-375 inhibited melanoma cell proliferation,
      invasion, and cell motility, and induced cell shape changes, strongly suggesting
      that miR-375 may have an important function in the development and progression of
      human melanomas.

PMID- 21723284
TI  - NELL-1 binds to APR3 affecting human osteoblast proliferation and
      differentiation.
AB  - Nel-like protein 1 (NELL-1) is an osteoinductive molecule associated with
      premature calvarial suture closure. Here we identified apoptosis related protein
      3 (APR3), a membrane protein known as a proliferation suppressor, as a binding
      protein of NELL-1 by biopanning. NELL-1 and APR3 colocalized on the nuclear
      envelope of human osteoblasts. NELL-1 significantly inhibited proliferation of
      osteoblasts co-transfected with APR3 through further down-regulation of Cyclin
      D1. The co-expression of NELL-1 and APR3 enhanced Ocn and Bsp expression and
      mineralization. RNAi of APR3 significantly reduced the differentiation effect of
      NELL-1. These findings suggest that the effects of NELL-1 on osteoblastic
      differentiation and proliferation are partly through binding to APR3.

PMID- 21723285
TI  - Recombinant human cytoplasmic dynein heavy chain 1 and 2: observation of dynein-2
      motor activity in vitro.
AB  - Cytoplasmic dynein is a microtubule (MT) motor protein comprising two classes:
      dynein-1 and dynein-2. We purified recombinant human dynein-1 and dynein-2 from
      HEK-293 cells by expressing the streptavidin-binding peptide-tagged human
      cytoplasmic dynein-1 and dynein-2 heavy chains (HCs), respectively. Electron
      microscopy of the purified molecules revealed a two-headed structure composed of
      characteristic dynein motor domains. In an in vitro MT gliding assay, both dynein
      1 and dynein-2 showed minus-end-directed motor activities. This is the first
      demonstration of dynein-2 motor activity, which supports the retrograde
      intraflagellar transport role of dynein-2. Our expression system of dynein HCs
      provides a useful means to investigate dynein functions.

PMID- 21723286
TI  - A case of punched-out ulcer occurring in the rectosigmoid colon with sudden onset
      of bloody stools.

PMID- 21723287
TI  - A novel expression and purification system for the production of enzymatic and
      biologically active human granzyme B.
AB  - The serine protease granzyme B (grB) has previously been shown to induce perforin
      independent apoptosis in membrane Hsp70 positive tumor cells in a number of in
      vitro experimental systems. Ongoing studies that are investigating the in vivo
      relevance of these findings by assessing the therapeutic potential of grB in a
      human xenograft tumor mouse model required the development of an expression
      system for the production of high yields of enzymatic and biologically active
      human grB. In order to maintain potentially important posttranslational
      modifications that occur in mammalian cells, human embryonal kidney cells
      (HEK293) were stably transfected with human grB. The HEK293 host cells were
      protected from apoptotic cell death by fusing an inactivation site coupled to a
      (His)(6) tag to the gene sequence of GrB. Inactive grB which was actively
      released from HEK293 cells by insertion of a Igkappa leader sequence was purified
      on a nickel column utilizing the (His)(6) tag. After enterokinase digestion and
      heparin affinity chromatography, high yields of enzymatic and biologically active
      human grB were obtained. The perforin-independent interaction of grB with
      membrane Hsp70 positive tumor cells appeared to be associated with mammalian
      glycosylation and mediated by the oligosaccharide moiety of neuraminic acid
      (NANA).

PMID- 21723288
TI  - Entomopathogenic nematodes, phoretic Paenibacillus spp., and the use of real time
      quantitative PCR to explore soil food webs in Florida citrus groves.
AB  - Quantitative real-time PCR (qPCR) is a powerful tool to detect and quantify
      species of cryptic organisms such as bacteria, fungi and nematodes from soil
      samples. As such, qPCR offers new opportunities to study the ecology of soil
      habitats by providing a single method to characterize communities of diverse
      organisms from a sample of DNA. Here we describe molecular tools to detect and
      quantify two bacteria (Paenibacillus nematophilus and Paenibacillus sp.)
      phoretically associated with entomopathogenic nematodes (EPNs) in the families
      Heterorhabditidae and Steinernematodae. We also extend the repertoire of species
      specific primers and TaqMan(r) probes for EPNs to include Heterorhabditis
      bacteriophora, Steinernema carpocapsae, Steinernema feltiae and Steinernema
      scapterisci, all widely distributed species used commercially for biological
      control. Primers and probes were designed from the ITS rDNA region for the EPNs
      and the 16S rDNA region for the bacteria. Standard curves were established using
      DNA from pure cultures of EPNs and plasmid DNA from the bacteria. The use of
      TaqMan probes in qPCR resolved the non-specificity of EPN and some bacterial
      primer amplifications whereas those for Paenibacillus sp. also amplified
      Paenibacillus thiaminolyticus and Paenibacillus popilliae, two species that are
      not phoretically associated with nematodes. The primer-probe sets for EPNs were
      able to accurately detect three infective juvenile EPNs added to nematodes
      recovered from soil samples. The molecular set for Paenibacillus sp. detected the
      bacterium attached to Steinernema diaprepesi suspended in water or added to
      nematodes recovered from soil samples but its detection decreased markedly in the
      soil samples, even when a nested PCR protocol was employed. Using qPCR we
      detected S. scapterisci at low levels in a citrus grove, which suggested natural
      long-distance spread of this exotic species, which is applied to pastures and
      golf courses to manage mole crickets (Scapteriscus spp.). Paenibacillus sp. (but
      not P. nematophilus) was detected in low quantities in the same survey but was
      unrelated to the spatial pattern of S. diaprepesi. The results of this research
      validate several new tools for studying the ecology of EPNs and their phoretic
      bacteria.

PMID- 21723290
TI  - Identification of 5-hydroxycytidine at position 2501 concludes characterization
      of modified nucleotides in E. coli 23S rRNA.
AB  - Complete characterization of a biomolecule's chemical structure is crucial in the
      full understanding of the relations between their structure and function. The
      dominating components in ribosomes are ribosomal RNAs (rRNAs), and the entire
      rRNA-but a single modified nucleoside at position 2501 in 23S rRNA-has previously
      been characterized in the bacterium Escherichia coli. Despite a first report
      nearly 20 years ago, the chemical nature of the modification at position 2501 has
      remained elusive, and attempts to isolate it have so far been unsuccessful. We
      unambiguously identify this last unknown modification as 5-hydroxycytidine-a
      novel modification in RNA. Identification of 5-hydroxycytidine was completed by
      liquid chromatography under nonoxidizing conditions using a graphitized carbon
      stationary phase in combination with ion trap tandem mass spectrometry and by
      comparing the fragmentation behavior of the natural nucleoside with that of a
      chemically synthesized ditto. Furthermore, we show that 5-hydroxycytidine is also
      present in the equivalent position of 23S rRNA from the bacterium Deinococcus
      radiodurans. Given the unstable nature of 5-hydroxycytidine, this modification
      might be found in other RNAs when applying the proper analytical conditions as
      described here.

PMID- 21723289
TI  - Autophagy as a therapeutic target in cardiovascular disease.
AB  - The epidemic of heart failure continues apace, and development of novel therapies
      with clinical efficacy has lagged. Now, important insights into the molecular
      circuitry of cardiovascular autophagy have raised the prospect that this cellular
      pathway of protein quality control may be a target of clinical relevance. Whereas
      basal levels of autophagy are required for cell survival, excessive levels - or
      perhaps distinct forms of autophagic flux - contribute to disease pathogenesis.
      Our challenge will be to distinguish mechanisms that drive adaptive versus
      maladaptive autophagy and to manipulate those pathways for therapeutic gain.
      Recent evidence suggests this may be possible. Here, we review the fundamental
      biology of autophagy and its role in a variety of forms of cardiovascular
      disease. We discuss ways in which this evolutionarily conserved catabolic
      mechanism can be manipulated, discuss studies presently underway in heart
      disease, and provide our perspective on where this exciting field may lead in the
      future. This article is part of a special issue entitled ''Key Signaling
      Molecules in Hypertrophy and Heart Failure.''

PMID- 21723291
TI  - Whole-molecule antibody engineering: generation of a high-affinity anti-IL-6
      antibody with extended pharmacokinetics.
AB  - The differentiation of therapeutic monoclonal antibodies in an increasingly
      competitive landscape requires optimization of clinical efficacy combined with
      increased patient convenience. We describe here the generation of MEDI5117, a
      human anti-interleukin (IL)-6 antibody generated by variable domain engineering,
      to achieve subpicomolar affinity for IL-6, combined with Fc (fragment
      crystallizable) engineering to enhance pharmacokinetic half-life. MEDI5117 was
      shown to be highly potent in disease-relevant cellular assays. The
      pharmacokinetics of MEDI5117 were evaluated and compared to those of its
      progenitor, CAT6001, in a single-dose study in cynomolgus monkeys. The antibodies
      were administered, either subcutaneously or intravenously, as a single dose of 5
      mg/kg. The half-life of MEDI5117 was extended by approximately 3-fold, and
      clearance was reduced by approximately 4-fold when compared to CAT6001. MEDI5117
      therefore represents a potential 'next-generation' antibody; future studies are
      planned to determine the potential for affinity-driven efficacy and/or less
      frequent administration.

PMID- 21723292
TI  - Dimeric plant RhoGAPs are regulated by its CRIB effector motif to stimulate a
      sequential GTP hydrolysis.
AB  - RopGAPs are GTPase-activating proteins (GAPs) for plant Rho proteins (ROPs). The
      largest RopGAP family is characterized by the plant-specific combination of a
      classical RhoGAP domain and a Cdc42/Rac interactive binding (CRIB) motif, which,
      in animal and fungi, has never been found in GAPs but in effectors for Cdc42 and
      Rac1. Very little is known about the molecular mechanism of the RopGAP activity
      including the regulatory role of the CRIB motif. Previously, we have shown that
      they are dimeric and form a 2:2 complex with ROPs. Here, we analyze the kinetics
      of the GAP-mediated GTP hydrolysis of ROPs using wild-type and mutant RopGAP2
      from Arabidopsis thaliana. For an efficient GAP activity, RopGAP2 requires both
      the catalytic Arg159 in its GAP domain indicating a similar catalytic machinery
      as in animal RhoGAPs and the CRIB motif, which mediates high affinity and
      specificity in binding. The dimeric RopGAP2 is unique in that it stimulates
      ROP.GTP hydrolysis in a sequential manner with a 10-fold difference between the
      hydrolysis rates of the two active sites. Using particular CRIB point and
      deletion mutants lead us to conclude that the sequential mechanism is likely due
      to steric hindrance induced by the Arg fingers and/or the CRIB motifs after
      binding of two ROP molecules.

PMID- 21723293
TI  - Distinct roles of overlapping and non-overlapping regions of hub protein
      interfaces in recognition of multiple partners.
AB  - Cellular functions of an organism are maintained by protein-protein interactions.
      Those proteins that bind multiple partners asynchronously (date hub proteins) are
      important to make the interaction network coordinated. It is known that many date
      hub proteins bind different partners at overlapping (OV) interfaces. To
      understand how OV interfaces of date hub proteins can recognize multiple
      partners, we analyzed the difference between OV and non-overlapping (Non-OV)
      regions of interfaces involved in the binding of different partners. By using the
      structures of 16 date hub proteins with various interaction partners (ranging
      from 5 to 33), we compared buried surface area, compositions of amino acid
      residues and secondary structures, and side-chain orientations. It was found that
      buried interface residues are important for recognizing multiple partners, while
      exposed interface residues are important for determining specificity to a
      particular ligand. In addition, our analyses reveal that residue compositions in
      OV and Non-OV regions are different and that residues in OV region show diverse
      side-chain torsion angles to accommodate binding to multiple targets.

PMID- 21723294
TI  - Modelling the effect of heterogeneity of shedding on the within herd Coxiella
      burnetii spread and identification of key parameters by sensitivity analysis.
AB  - Coxiella burnetii is the bacterium responsible for Q fever, a worldwide zoonosis.
      Ruminants, especially cattle, are recognized as the most important source of
      human infections. Although a great heterogeneity between shedder cows has been
      described, no previous studies have determined which features such as shedding
      route and duration or the quantity of bacteria shed have the strongest impact on
      the environmental contamination and thus on the zoonotic risk. Our objective was
      to identify key parameters whose variation highly influences C. burnetii spread
      within a dairy cattle herd, especially those related to the heterogeneity of
      shedding. To compare the impact of epidemiological parameters on different
      dynamical aspects of C. burnetii infection, we performed a sensitivity analysis
      on an original stochastic model describing the bacterium spread and representing
      the individual variability of the shedding duration, routes and intensity as well
      as herd demography. This sensitivity analysis consisted of a principal component
      analysis followed by an ANOVA. Our findings show that the most influential
      parameters are the probability distribution governing the levels of shedding,
      especially in vaginal mucus and faeces, the characteristics of the bacterium in
      the environment (i.e. its survival and the fraction of bacteria shed reaching the
      environment), and some physiological parameters related to the intermittency of
      shedding (transition probability from a non-shedding infected state to a shedding
      state) or to the transition from one type of shedder to another one (transition
      probability from a seronegative shedding state to a seropositive shedding state).
      Our study is crucial for the understanding of the dynamics of C. burnetii
      infection and optimization of control measures. Indeed, as control measures
      should impact the parameters influencing the bacterium spread most, our model can
      now be used to assess the effectiveness of different control strategies of Q
      fever within dairy cattle herds.

PMID- 21723295
TI  - Negative feedback and physical limits of genes.
AB  - This paper compares the auto-repressed gene to a simple one (a gene without auto
      regulation) in terms of response time and output noise under the assumption of
      fixed metabolic cost. The analysis shows that, in the case of non-vanishing leak
      expression rate, the negative feedback reduces both the switching on and
      switching off times of a gene. The noise of the auto-repressed gene will be lower
      than the one of the simple gene only for low leak expression rates. Summing up,
      for low, but non-vanishing leak expression rates, the auto-repressed gene is both
      faster and less noisier compared to the simple one.

PMID- 21723296
TI  - Effect of localization, length and orientation of chondrocytic primary cilium on
      murine growth plate organization.
AB  - The research investigates the role of the immotile chondrocytic primary cilium in
      the growth plate. This study was motivated by (i) the recent evidence of the
      mechano-sensorial function of the primary cilium in kidney tubule epithelial
      cells and (ii) the distinct three-dimensional orientation patterns that the
      chondrocytic primary cilium forms in articular cartilage in the presence or the
      absence of loading. For our investigation, we used the Smad1/5(CKO) mutant mouse,
      whose disorganized growth plate is due to the conditional deletion of Smad 1 and
      5 proteins that also affect the so-called Indian Hedgehog pathway, whose physical
      and functional topography has been shown to be partially controlled by the
      primary cilium. Fluorescence and confocal microscopy on stained sections
      visualized ciliated chondrocytes. Morphometric data regarding position,
      orientation and eccentricity of chondrocytes, and ciliary localization on cell
      membrane, length and orientation, were collected and reconstructed from images.
      We established that both localization and orientation of the cilium are definite,
      and differently so, in the Smad1/5(CKO) and control mice. The orientation of the
      primary cilium, relative to the major axis of the chondrocyte, clusters at 80
      degrees  with respect to the anterior-posterior direction for the Smad1/5(CKO)
      mice, showing loss of the additional clustering present in the control mice at 10
      degrees . We therefore hypothesized that the clustering at 10 degrees  contains
      information of columnar organization. To test our hypothesis, we prepared a
      mathematical model of relative positioning of the proliferative chondrocytic
      population based on ciliary orientation. Our model belongs to the category of
      "interactive particle system models for self-organization with birth". The model
      qualitatively reproduced the experimentally observed chondrocytic arrangements in
      growth plate of each of the Smad1/5(CKO) and control mice. Our mathematically
      predicted cell division process will need to be observed experimentally to
      advance the identification of ciliary function in the growth plate.

PMID- 21723297
TI  - Cross-bridge kinetics in myofibrils containing familial hypertrophic
      cardiomyopathy R58Q mutation in the regulatory light chain of myosin.
AB  - Familial hypertrophic cardiomyopathy (FHC) is a heritable form of cardiac
      hypertrophy caused by single-point mutations in genes encoding sarcomeric
      proteins including ventricular myosin regulatory light chain (RLC). FHC often
      leads to malignant outcomes and sudden cardiac death. The FHC mutations are
      believed to alter the kinetics of the interaction between actin and myosin
      resulting in inefficient energy utilization and compromised function of the
      heart. We studied the effect of the FHC-linked R58Q-RLC mutation on the kinetics
      of transgenic (Tg)-R58Q cardiac myofibrils. Kinetics was determined from the rate
      of change of orientation of actin monomers during muscle contraction. Actin
      monomers change orientation because myosin cross-bridges deliver periodic force
      impulses to it. An individual impulse (but not time average of impulses) carries
      the information about the kinetics of actomyosin interaction. To observe
      individual impulses it was necessary to scale down the experiments to the level
      of a few molecules. A small population (~4 molecules) was selected by using
      (deliberately) inefficient fluorescence labeling and observing fluorescent
      molecules by a confocal microscope. We show that the kinetic rates are
      significantly smaller in the contracting cardiac myofibrils from Tg-R58Q mice
      then in control Tg-wild type (WT). We also demonstrate a lower force per cross
      section of muscle fiber in Tg-R58Q versus Tg-WT mice. We conclude that the R58Q
      mutation-induced decrease in cross-bridge kinetics underlines the mechanism by
      which Tg-R58Q fibers develop low force and thus compromise the ability of the
      mutated heart to efficiently pump blood.

PMID- 21723299
TI  - Review: Game theory of public goods in one-shot social dilemmas without
      assortment.
AB  - We review the theory of public goods in biology. In the N-person prisoner's
      dilemma, where the public good is a linear function of the individual
      contributions, cooperation requires some form of assortment, for example due to
      kin discrimination, population viscosity or repeated interactions. In most social
      species ranging from bacteria to humans, however, public goods are usually a non
      linear function of the contributions, which makes cooperation possible without
      assortment. More specifically, a polymorphic state can be stable in which
      cooperators and non-cooperators coexist. The existence of mixed equilibria in
      public goods games is a fundamental result in the study of cooperation that has
      been overlooked so far, because of the disproportionate attention given to the
      two- and N-person prisoner's dilemma. Methods and results from games with
      pairwise interactions or linear benefits cannot, in general, be extended to the
      analysis of public goods. Game theory helps explain the production of public
      goods in one-shot, N-person interactions without assortment, it leads to
      predictions that can be easily tested and allows a prescriptive approach to
      cooperation.

PMID- 21723298
TI  - New powerful statistics for alignment-free sequence comparison under a pattern
      transfer model.
AB  - Alignment-free sequence comparison is widely used for comparing gene regulatory
      regions and for identifying horizontally transferred genes. Recent studies on the
      power of a widely used alignment-free comparison statistic D2 and its variants
      D*2 and D(s)2 showed that their power approximates a limit smaller than 1 as the
      sequence length tends to infinity under a pattern transfer model. We develop new
      alignment-free statistics based on D2, D*2 and D(s)2 by comparing local sequence
      pairs and then summing over all the local sequence pairs of certain length. We
      show that the new statistics are much more powerful than the corresponding
      statistics and the power tends to 1 as the sequence length tends to infinity
      under the pattern transfer model.

PMID- 21723300
TI  - A stochastic approach to risk management for prostate cancer patients on active
      surveillance.
AB  - Screening for prostate cancer (PC) has led to more cancers being detected at
      early stages, where active surveillance (AS), a strategy that involves monitoring
      and intervention when the disease progresses, is an option. Physicians are
      seeking ways to measure progression of the disease such that AS is abandoned when
      appropriate. A blood test, prostate-specific antigen (PSA), and the concept of
      doubling time (PSADT) and PSA kinetics are being used as proxies of disease speed
      of progression. Studies using these proxies report conflicting results. These
      studies cast doubts on the current rules for stopping AS and recent research
      concludes that PSADT and PSA kinetics are unreliable triggers for intervention in
      an AS program. These findings are consistent with stochastic processes being
      analyzed as if they were "deterministic" (i.e., current models measure disease
      progression by PSA's evolution assuming it to be deterministic). A model that
      best describes PSA evolution is a pre-requisite to the establishment of decision
      criteria for abandoning AS. This paper suggests modeling PSA evolutions and
      kinetics as stochastic processes. Consequently, triggers for stopping AS may be
      different than PSADT and can result in substantially different recommendations,
      which are likely to have significant impact on patients and the healthcare
      system.

PMID- 21723301
TI  - A novel canonical dual computational approach for prion AGAAAAGA amyloid fibril
      molecular modeling.
AB  - Many experimental studies have shown that the prion AGAAAAGA palindrome
      hydrophobic region (113-120) has amyloid fibril forming properties and plays an
      important role in prion diseases. However, due to the unstable, noncrystalline
      and insoluble nature of the amyloid fibril, to date structural information on
      AGAAAAGA region (113-120) has been very limited. This region falls just within
      the N-terminal unstructured region PrP (1-123) of prion proteins. Traditional X
      ray crystallography and nuclear magnetic resonance (NMR) spectroscopy
      experimental methods cannot be used to get its structural information. Under this
      background, this paper introduces a novel approach of the canonical dual theory
      to address the 3D atomic-resolution structure of prion AGAAAAGA amyloid fibrils.
      The novel and powerful canonical dual computational approach introduced in this
      paper is for the molecular modeling of prion AGAAAAGA amyloid fibrils, and that
      the optimal atomic-resolution structures of prion AGAAAAGA amyloid fibils
      presented in this paper are useful for the drive to find treatments for prion
      diseases in the field of medicinal chemistry. Overall, this paper presents an
      important method and provides useful information for treatments of prion
      diseases.

PMID- 21723302
TI  - Highly accurate computation of dynamic sensitivities in metabolic reaction
      systems by a Taylor series method.
AB  - We have previously developed the software for calculation of dynamic
      sensitivities, SoftCADS, in which one can calculate dynamic sensitivities with
      high accuracy by just setting the differential equations for metabolite
      concentrations. However, SoftCADS did not always provide calculated values with
      the machine accuracy of a computer, although a Taylor series method was employed
      to numerically solve the differential equations. This is because numerical
      derivatives calculated from an approximate formula were directly used in the
      derivation of the differential equations for sensitivities from those for
      metabolite concentrations. The present work therefore attempts to further enhance
      the performance of SoftCADS, including not only the accuracies of the calculated
      values but also the calculation time. To overcome the problem, the approximate
      formula is expanded into a Taylor series in time and the first-term value of the
      series is replaced by the exact coefficient on the second term of the flux
      function expanded into a Taylor series in an independent or dependent variable.
      The result reveals that this replacement certainly provides not only numerical
      derivatives but also dynamic sensitivities with superhigh accuracies comparable
      to the machine accuracy, regardless of the degree of stiffness of the
      differential equations. Moreover, a comparison indicates that the improved
      SoftCADS shortens the calculation time of the dynamic sensitivities without
      reducing their accuracies, even when the simplest approximate derivative formula
      is used.

PMID- 21723303
TI  - A critical test of the hippocampal theta model of anxiolytic drug action.
AB  - Hippocampal theta rhythms have been associated with a number of behavioural
      processes, including learning, memory and arousal. Recently it has been argued
      that the suppression of hippocampal theta is a valid indicator of anxiolytic drug
      action. Like all such models, however, it has relied almost exclusively on the
      experimental effects of well-known, clinically proven anxiolytic compounds for
      validation. The actual predictive validity of putative models of anxiolytic drug
      action, however, cannot be rigorously tested with this approach alone. The
      present study provides a stringent test of the predictive validity of the theta
      suppression model, using the drug phenytoin (50 mg/kg and 10 mg/kg), and a
      positive comparison compound, diazepam (2 mg/kg). Phenytoin has two important
      properties that are advantageous for assessing the validity of the theta
      suppression model: 1) it is a standard antiepileptic drug with no known
      anxiolytic effects, and 2) its primary mechanism of action is through suppression
      of the persistent sodium current, an effect that should also suppress hippocampal
      theta. Because of the latter property, we also directly compared the effects of
      phenytoin in the theta suppression model with its effects in the most widely
      tested behavioural model of anxiolytic drug action, the elevated plus-maze. While
      an anxiolytic-like effect of phenytoin in the theta suppression model might be
      expected simply due to its suppressive effects on sodium channel currents,
      anxiolytic effects in both tests would provide strong support for the predictive
      validity of the theta suppression model. Surprisingly, phenytoin produced clear
      anxiolytic-like effects in both neurophysiological and behavioural models, thus
      providing strong evidence of the predictive validity of the theta suppression
      model. This article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21723304
TI  - Narrative language in traumatic brain injury.
AB  - Persons with traumatic brain injury (TBI) often show impaired linguistic and/or
      narrative abilities. The present study aimed to document the features of
      narrative discourse impairment in a group of adults with TBI. 14 severe TBI non
      aphasic speakers (GCS<8) in the phase of neurological stability and 14
      neurologically intact participants were recruited for the experiment. Their
      cognitive, linguistic and narrative skills were thoroughly assessed. The group of
      non-aphasic individuals with TBI had normal lexical and grammatical skills.
      However, they produced narratives with increased errors of cohesion and coherence
      due to the frequent interruption of ongoing utterances, derailments and
      extraneous utterances that made their discourse vague and ambiguous. They
      produced a normal amount of thematic units (i.e. concepts) in their narratives.
      However, this information was not correctly organized at micro- and
      macrolinguistic levels of processing. A Principal Component Analysis showed that
      a single factor accounted for the production of global coherence errors, and the
      reduction of both propositional density at the utterance level and proportion of
      words that conveyed information. It is hypothesized that the linguistic deficits
      observed in the participants with TBI may reflect a deficit at the interface
      between cognitive and linguistic processing rather than a specific linguistic
      disturbance.

PMID- 21723305
TI  - Effects of recovery from immobilization stress on striatal preprodynorphin- and
      kappa opioid receptor-mRNA levels of the male rat.
AB  - Previously, we have reported that brain regions that are thought to be involved
      in motivated behavior are altered in animals undergoing repeated exposures to
      immobilization stress. The goal of the present study was to determine the effects
      of recovery from this type of stress on these same mesolimbic brain regions. For
      this purpose, adult male Sprague-Dawley rats were initially exposed to
      immobilization stress either once (2 h) or repeatedly (2 h*10 days). Rats were
      then either allowed to recover from the stressor for a shorter (2 days) or longer
      period of time (9 days) in their home cages. At the end of this recovery period,
      rats were euthanized and trunk blood and brains were processed for serum
      corticosterone (CORT) and neurochemistry, respectively. Brain mRNA levels were
      determined via in situ hybridization for the opioid preprodynorphin (DYN) and its
      cognate receptor (kappa, KOR), in striatal and accumbal subregions. A pattern of
      selective transcriptional activation emerged in the four resultant treatment
      conditions where a short recovery from either a single or repeated exposure to
      immobilization produced increases in KOR-mRNA levels in striatal and nucleus
      accumbens (Acb) subregions. Relative to controls, these differences were
      diminished after a longer recovery period. Interestingly, DYN-mRNA levels were
      unchanged after the shorter recovery period and after single or repeated
      immobilizations but appeared to be induced after a longer recovery period after
      repeated immobilizations. A relative amount of weight loss occurred after
      immobilization following repeated but not single exposure to stress. In addition,
      only those rats recovering from repeated stress exposures had higher CORT levels
      compared with non-immobilized controls. These results suggest that recovery from
      immobilization stress may alter the motivational system after as little as a
      single immobilization and that a possible dysphoric effect on appetitive behavior
      may be reflected by an altered striatal dynorphin system.

PMID- 21723306
TI  - Protection against 2-chloroethyl ethyl sulfide (CEES)-induced cytotoxicity in
      human keratinocytes by an inducer of the glutathione detoxification pathway.
AB  - Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent
      almost 100years ago. Due to its toxic effects on the eyes, lungs, and skin, and
      the relative ease with which it may be synthesized, mustard gas remains a
      potential chemical threat to the present day. SM exposed skin develops fluid
      filled bullae resulting from potent cytotoxicity of cells lining the basement
      membrane of the epidermis. Currently, there are no antidotes for SM exposure;
      therefore, chemopreventive measures for first responders following an SM attack
      are needed. Glutathione (GSH) is known to have a protective effect against SM
      toxicity, and detoxification of SM is believed to occur, in part, via GSH
      conjugation. Therefore, we screened 6 potential chemopreventive agents for
      ability to induce GSH synthesis and protect cultured human keratinocytes against
      the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human
      keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12
      dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2
      and induced expression of the GSH synthesis gene, GCLM. Additionally, we found
      that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and
      preserved their viability by ~3-fold following exposure to CEES. Our data also
      suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a
      nucleophilic scavenging agent, to increase the viability of keratinocytes exposed
      to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent
      for SM toxicity in the skin.

PMID- 21723307
TI  - Exposure to low mercury concentration in vivo impairs myocardial contractile
      function.
AB  - Increased cardiovascular risk after mercury exposure has been described but
      cardiac effects resulting from controlled chronic treatment are not yet well
      explored. We analyzed the effects of chronic exposure to low mercury
      concentrations on hemodynamic and ventricular function of isolated hearts. Wistar
      rats were treated with HgCl2 (1st dose 4.6 MUg/kg, subsequent dose 0.07
      MUg/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood
      pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry
      and collagen content. This treatment: 1) in vivo increased left ventricle end
      diastolic pressure (LVEDP) without changing left ventricular systolic pressure
      (LVSP) and heart rate; 2) in isolated hearts reduced LV isovolumic systolic
      pressure and time derivatives, and beta-adrenergic response; 3) increased myosin
      ATPase activity; 4) reduced Na+-K+ ATPase (NKA) activity; 5) reduced protein
      expression of SERCA and phosphorylated phospholamban on serine 16 while
      phospholamban expression increased; as a consequence SERCA/phospholamban ratio
      reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and alpha-1
      isoform of NKA, whereas alpha-2 isoform of NKA did not change. Chronic exposure
      for 30 days to low concentrations of mercury does not change BP, heart rate or
      LVSP but produces small but significant increase of LVEDP. However, in isolated
      hearts mercury treatment promoted contractility dysfunction as a result of the
      decreased NKA activity, reduction of NCX and SERCA and increased PLB protein
      expression. These findings offer further evidence that mercury chronic exposure,
      even at small concentrations, is an environmental risk factor affecting heart
      function.

PMID- 21723308
TI  - Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol
      treated female rats.
AB  - Carvacrol is the major constituent of essential oils from aromatic plants. It
      showed antimicrobial, anticancer and antioxidant properties. Although it was
      approved for food use and included in the chemical flavorings list, no indication
      on its safety has been estimated. Since the use of plant extracts is relatively
      high among women, aim of this study was to evaluate carvacrol effects on female
      physiology and endocrine profiles by using female rats in proestrus and diestrus
      phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus
      accumbens, after carvacrol administration (0.15 and 0.45g/kg p.o.), was measured.
      Drug effects in behavioral tests for alterations in motor activity, depression,
      anxiety-related behaviors and endocrine alterations were also investigated. While
      in proestrus carvacrol reduced serotonin and metabolite levels in both brain
      areas, no effects were observed in diestrus phase. Only in proestrus phase,
      carvacrol induced a depressive-like behavior in forced swimming test, without
      accompanying changes in ambulation. The improvement of performance in FST after
      subchronic treatment with fluoxetine (20mg/kg) suggested a specific involvement
      of serotonergic system. No differences were found across the groups with regard
      to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only
      estradiol levels without binding hypothalamic estradiol receptors. Our study
      showed an estrous-stage specific effect of carvacrol on depressive behaviors and
      endocrine parameters, involving serotonergic system. Given the wide carvacrol use
      not only as feed additive, but also as cosmetic essence and herbal remedy, our
      results suggest that an accurate investigation on the effects of its chronic
      exposure is warranted.

PMID- 21723310
TI  - Crotoxin and phospholipases A2 from Crotalus durissus terrificus showed antiviral
      activity against dengue and yellow fever viruses.
AB  - Dengue is the most important arbovirus in the world with an estimated of 50
      million dengue infections occurring annually and approximately 2.5 billion people
      living in dengue endemic countries. Yellow fever is a viral hemorrhagic fever
      with high mortality that is transmitted by mosquitoes. Effective vaccines against
      yellow fever have been available for almost 70 years and are responsible for a
      significant reduction of occurrences of the disease worldwide; however,
      approximately 200,000 cases of yellow fever still occur annually, principally in
      Africa. Therefore, it is a public health priority to develop antiviral agents for
      treatment of these virus infections. Crotalus durissus terrificus snake, a South
      American rattlesnake, presents venom with several biologically actives molecules.
      In this study, we evaluated the antiviral activity of crude venom and isolated
      toxins from Crotalus durissus terrificus and found that phospholipases A2 showed
      a high inhibition of Yellow fever and dengue viruses in VERO E6 cells.

PMID- 21723309
TI  - Exposure to tri-o-cresyl phosphate detected in jet airplane passengers.
AB  - The aircraft cabin and flight deck ventilation are supplied from partially
      compressed unfiltered bleed air directly from the engine. Worn or defective
      engine seals can result in the release of engine oil into the cabin air supply.
      Aircrew and passengers have complained of illness following such "fume events".
      Adverse health effects are hypothesized to result from exposure to tricresyl
      phosphate mixed esters, a chemical added to jet engine oil and hydraulic fluid
      for its anti-wear properties. Our goal was to develop a laboratory test for
      exposure to tricresyl phosphate. The assay was based on the fact that the active
      site serine of butyrylcholinesterase reacts with the active metabolite of tri-o
      cresyl phosphate, cresyl saligenin phosphate, to make a stable phosphorylated
      adduct with an added mass of 80 Da. No other organophosphorus agent makes this
      adduct in vivo on butyrylcholinesterase. Blood samples from jet airplane
      passengers were obtained 24-48 h after completing a flight. Butyrylcholinesterase
      was partially purified from 25 ml serum or plasma, digested with pepsin, enriched
      for phosphorylated peptides by binding to titanium oxide, and analyzed by mass
      spectrometry. Of 12 jet airplane passengers tested, 6 were positive for exposure
      to tri-o-cresyl phosphate that is, they had detectable amounts of the
      phosphorylated peptide FGEpSAGAAS. The level of exposure was very low. No more
      than 0.05 to 3% of plasma butyrylcholinesterase was modified. None of the
      subjects had toxic symptoms. Four of the positive subjects were retested 3 to 7
      months following their last airplane trip and were found to be negative for
      phosphorylated butyrylcholinesterase. In conclusion, this is the first report of
      an assay that detects exposure to tri-o-cresyl phosphate in jet airplane
      travelers.

PMID- 21723311
TI  - Magnocellular and parvocellular influences on reflexive attention.
AB  - Previous studies have provided conflicting evidence regarding whether the
      magnocellular (M) or parvocellular (P) visual pathway is primarily responsible
      for triggering involuntary orienting. Here, we used event-related potentials
      (ERPs) to provide new evidence that both the M and P pathways can trigger
      attentional capture and bias visual processing at multiple levels. Specifically,
      cued-location targets elicited enhanced activity, relative to uncued-location
      targets, at both early sensory processing levels (indexed by the P1 component)
      and later higher-order processing stages (as indexed by the P300 component).
      Furthermore, the present results show these effects of attentional capture were
      not contingent on the feature congruency between the cue and expected target,
      providing evidence that this biasing of visual processing was not dependant on
      top-down expectations or within-pathway priming.

PMID- 21723312
TI  - How do we achieve informed choice for women considering breast screening?
AB  - OBJECTIVE: In current medical literature, mammography and other cancer screening
      programs are subject to controversy because of debate about the magnitude and
      nature of the benefits and harms. This paper discusses the issues around informed
      choice for women considering breast screening. METHOD: We discuss qualitative and
      quantitative studies of women's attitudes to breast screening and informed
      choice. RESULTS: Women view breast screening as a way of avoiding potential
      regret, and reassurance from normal results is highly valued. Screening
      participants acknowledge anxiety about false positives but awareness regarding
      potential overdetection of indolent breast cancer is minimal, and research is
      needed to assess how better understanding of screening downsides may affect
      women's views. In any case, weighing up screening advantages and disadvantages is
      sensitive to personal preferences. CONCLUSIONS: Communicators have an ethical
      obligation to make balanced information available to women, which is flexible
      enough to respond to the level of detail and involvement desired by each
      individual. Many women want to know more and to participate more actively in
      screening decisions. Techniques have been developed to present balanced
      information and support individual decision making in ways that are accessible
      and empowering for the wider community. Evaluations of breast cancer screening
      must integrate clinical data with evidence on the perspectives of women
      themselves.

PMID- 21723313
TI  - Impact of age-specific recommendation changes on organized breast screening
      programs.
AB  - BACKGROUND: Recent changes in recommendations for mammography screening for women
      in their forties could have an impact on organized screening programs, as these
      require clear definition of target and eligible populations. CURRENT STATUS:
      Internationally, a majority of programs target women fifty and over, and so the
      recent USPSTF age recommendations for screening are quite consistent with this
      practice. However, there is a good deal of variability in the availability of
      population-based screening programs to women in their forties should they choose
      to participate. FUTURE IMPACT: Several programs are reviewing recommendations
      regarding the eligibility of women in their forties; as guidelines indicate women
      in this age group should be eligible for screening, even if not targeted, there
      is discussion as to whether they should be allowed in programs so that they
      benefit from the same programmatic quality assurance afforded to the target
      population of women over 50. Clear communication of the evidentiary basis for the
      eligibility criteria and target populations is required, so that the public is
      aware that programs are designed to deliver maximal population impact, while
      minimizing population risk.

PMID- 21723314
TI  - Inhibitory effect of Sargassum polysaccharide on oxidative stress induced by
      infectious bursa disease virus in chicken bursal lymphocytes.
AB  - The aim of this study was to investigate the inhibitory effect of Sargassum
      polysaccharide on oxidative stress induced by infectious bursa disease virus
      (IBDV) in chicken bursal lymphocytes. The levels of IL-1beta, IL-8, IL-10, TNF
      alpha, MCP-1, reduced glutathione and reactive oxygen species in chicken bursal
      lymphocytes treated with IBDV or both IBDV and Sargassum polysaccharide were
      measured, and the activities of superoxide dimutase and glutathione peroxidase
      were evaluated. Our results showed that oxidative stress appeared when chicken
      bursal lymphocytes were incubated with IBDV for 8h at 100 TCID(50). Sargassum
      polysaccharide inhibited oxidative stress by increasing the amount of reduced
      glutathione, promoting the activities of superoxide dimutase and glutathione
      peroxidase and reducing the level of reactive oxygen species. The polysaccharide
      also raised IL-1beta, IL-8, IL-10 and TNF-alpha levels in cells infected with
      IBDV. These findings suggest that Sargassum polysaccharide acts against infection
      by elevating antioxidant capacity and cytokine levels in chicken bursal
      lymphocytes.

PMID- 21723315
TI  - Anti-hypoxia activity of a polysaccharide extracted from the Sipunculus nudus L.
AB  - A water-soluble polysaccharide, named as SNP, was extracted and fractioned from
      the body wall of Sipunculus nudus L. by DEAE-Sepharose anion exchange and
      Sepharose CL-6B column chromatography. The evaluation for anti-hypoxia activity
      demonstrated that SNP had significant anti-hypoxic activity on normobarie
      hypoxia, chemical intoxicant hypoxia and acute cerebral ischemia hypoxia models
      in mice. SNP also enhanced the number of red blood cell count (RBC) and the
      concentration of hemoglobin (HGB). The structural characteristics of SNP
      investigated by high performance size exclusion chromatography, Fourier transform
      infrared spectroscopy and gas chromatography-mass spectrometry indicated that SNP
      was a homogeneous polysaccharide with a molecular mass of 350 kD and was composed
      of rhamnose (28%), fucose (16%) and galactose (56%). The results suggested that
      SNP could be explored as a novel potential anti-hypoxia agent.

PMID- 21723316
TI  - Two high-copy plasmids found in plants associated with strains of "Candidatus
      Phytoplasma asteris".
AB  - Complete sequences for two plasmids associated with two strains of "Candidatus
      Phytoplasma asteris" have been obtained. The plasmid named pPARG1 was found in
      Rehmannia glutinosa L. associated with phytoplasma classified in the 16Sr I-C
      subgroup. Plasmid pPABN1 was from phytoplasma associated with infected winter
      oilseed rape and classified in the 16Sr I-B subgroup. The plasmids pPARG1 (4371
      nt) and pPABN1 (3529 nt) have high A+T content of about 75%, similar to that of
      phytoplasma genomes. Six and five open reading frames longer than 100 amino acids
      and organized on the same strand were recognized on pPARG1 and pPABN1,
      respectively. A segment about 1.6 kbp long sharing high sequence identity with
      the Onion yellows phytoplasma genome was found in pPABN1.

PMID- 21723317
TI  - Smoking, quitting, and psychiatric disease: a review.
AB  - Tobacco smoking among patients with psychiatric disease is more common than in
      the general population, due to complex neurobiological, psychological, and
      pharmacotherapeutic mechanisms. Nicotine dependence exposes smokers with co
      occurring mental illness to increased risks of smoking-related morbidity,
      mortality, and to detrimental impacts on their quality of life. The
      neurobiological and psychosocial links to smoking appear stronger in certain
      comorbidities, notably depression and schizophrenia. Through its action on the
      cholinergic system, nicotine may have certain beneficial effects across a range
      of mental health domains in these patients, including improved concentration and
      cognition, relief of stress and depressive affect, and feeling pleasurable
      sensations. Despite the availability of effective smoking cessation
      pharmacotherapies and psychosocial interventions, as well as increasing evidence
      that individuals with psychiatric disorders are motivated to quit, nicotine
      dependence remains an undertreated and under-recognized problem within this
      patient population. Evidence suggests that provision of flexible and
      individualized treatment programs may be successful. Furthermore, the complicated
      relationship observed between nicotine dependence, nicotine withdrawal symptoms,
      and mental illness necessitates integration of close monitoring in any successful
      smoking cessation program.

PMID- 21723318
TI  - Effects of K074 and pralidoxime on antioxidant and acetylcholinesterase response
      in malathion-poisoned mice.
AB  - The organophosphorus (OP) pesticide malathion is a highly neurotoxic compound and
      its toxicity is primarily caused by the inhibition of acetylcholinesterase
      (AChE), leading to cholinergic syndrome. Although oximes have been used as
      potential antidotal treatments in malathion poisoning because of their potential
      capability to reactivate the inhibited enzyme, the clinical experience with the
      clinically available oximes (e.g. pralidoxime) is disappointing and their routine
      use has been questioned. In the present study, we investigated the potency of
      pralidoxime and K074 in reactivating AChE after acute exposure to malathion, as
      well as in preventing malathion-induced changes in oxidative-stress related
      parameters in mice. Malathion (1.25 g/kg, s.c.) induced a significant decrease in
      cortico-cerebral, hippocampal and blood AChE activities at 24h after exposure.
      Oxime treatments (1/4 of LD(50), i.m., 6h after malathion poisoning) showed that
      pralidoxime significantly reversed malathion-induced blood AChE inhibition,
      although no significant effects were observed after K074 treatment.
      Interestingly, both oximes tested were unable to reactivate the cortico-cerebral
      and hippocampal enzymes after intramuscular or intracerebroventricular injection
      (1/4 of LD(50), 6h after malathion poisoning). Biochemical parameters related to
      oxidative stress (cerebro-cortical and hippocampal glutathione peroxidase,
      glutathione reductase and catalase activities, as well as lipid peroxidation)
      were not affected in animals treated with malathion, oximes or atropine alone.
      However, pralidoxime and K074, administered intramuscularly 6h after malathion
      poisoning, were able to increase the endogenous activities of these antioxidant
      enzymes in the prefrontal cortex and hippocampus. Taken together, the results
      presented herein showed that pralidoxime (the most common clinically used oxime)
      and the recently developed oxime K074, administered 6h after malathion poisoning,
      were unable to reactivate the inhibited AChE in mouse prefrontal cortex and
      hippocampus. However, only pralidoxime significantly reversed the blood AChE
      inhibition induced by malathion poisoning. This indicates that peripheral and
      central AChE activities are not necessarily correlated after the treatment of OP
      compounds and/or oximes, which should be taken into account in the diagnosis and
      management of OP-exposed humans. In addition, considering that the available
      treatments to malathion poisoning appear to be ineffective, the present study
      reinforce the need to search for potential new AChE reactivators able to
      efficiently reactivate the brain and blood AChEs after malathion poisoning.

PMID- 21723319
TI  - Increased efficacy of the 6-hydroxydopamine lesion of the median forebrain bundle
      in small rats, by modification of the stereotaxic coordinates.
AB  - The 6-hydroxydopamine (6-OHDA) lesion is the most widely used rat model of
      Parkinson's disease. A single unilateral injection of 6-OHDA into the median
      forebrain bundle (MFB) selectively destroys dopamine neurons in the ipsilateral
      substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), removing
      more than 95% of the dopamine innervation from target areas. The stereotaxic
      coordinates used to deliver 6-OHDA to the MFB have been used in our laboratory
      successfully for more than 25 years. However, in recent years we have observed a
      decline in the success rate of this lesion. Previously regular success rates of
      >80% of rats lesioned, have become progressively more variable, with rates as low
      as 20% recorded in some experiments. Having excluded variability of the
      neurotoxin and operator errors, we hypothesized that the change seen might be due
      to the use of smaller rats at the time of first surgery. An attempt to
      proportionally adjust the lesion coordinates base on head size did not increase
      lesion efficacy. However, in support of the small rat hypothesis it was observed
      that, using the standard coordinates, rat's heads had a "nose-up" position in the
      stereotaxic fame. Adjustment of the nose bar to obtain a flat head position
      during surgery improved lesion success, and subsequent adjustments of the lesion
      coordinates to account for smaller head size led to a greatly increased lesion
      efficacy (>90%) as assessed by amphetamine induced rotation.

PMID- 21723320
TI  - A surgical device for minimally invasive implantation of experimental deep brain
      stimulation leads in large research animals.
AB  - BACKGROUND: Deep brain stimulation (DBS) in experimental animals has promoted new
      indications and refined existing treatments. Implantation of downscaled clinical
      DBS leads directly compatible with commercially available implantable pulse
      generators can however be challenging. Accordingly, we have developed a lead
      implantation device (LID) and technique for minimally invasive implantation of
      experimental multicontact DBS leads in large research animals. MATERIALS AND
      METHODS: The LID carries a small-diameter biocompatible polyimide guide tube
      which is first used for inserting the stimulating end of the lead and then
      implanted subcutaneously with the rest of the lead. The functionality of the
      device was tested by implanting 2 different designs of experimental DBS leads in
      12 Gottingen minipigs for up to 12 weeks. The brains were histologically analyzed
      in order to assess implantation accuracy and local tissue reaction. RESULTS AND
      CONCLUSIONS: The LID was easy to handle and capable of accurate stereotaxic
      implantation of downscaled experimental DBS leads in the predetermined target
      brain structures with minimal surrounding tissue reaction. The device may benefit
      future large animal DBS research as it allows for precise implantation of DBS
      leads and may have implications for further refinement of clinical DBS leads.

PMID- 21723321
TI  - Microbore liquid chromatography with UV detection to study the in vivo passage of
      compound 21, a non-peptidergic AT2 receptor agonist, to the striatum in rats.
AB  - A microbore liquid chromatography method coupled to UV detection was developed
      and validated in order to monitor the passage of compound 21 (C21), a non-peptide
      angiotensin II type 2 receptor agonist, to the striatum of rats. For this
      purpose, sampling from the striatum was performed using the in vivo microdialysis
      technique. Separations were performed on a C18 microbore (1mm i.d.) column using
      gradient elution. The retention time for C21 was found to be 6.3 min. The
      calibration curve was linear between 10 and 200 ng/ml with a correlation
      coefficient >= 0.999. The limit of detection and the limit of quantification were
      3 and 10 ng/ml respectively. The intra-day and the inter-day precision (RSD%)
      ranged between 0.5 and 4.6% with an average recovery of 101.5+/-10.0% (mean+/-SD,
      n=15). In vivo experiments were performed on rats to measure the concentration of
      C21 in striatal dialysates after intraperitoneal (10 or 50mg/kg) or intravenous
      injection (10 mg/kg or 20 mg/kg) of C21 and suggest minimal passage of the
      compound to the striatum.

PMID- 21723322
TI  - Catheterization of the thoracic spinal subarachnoid space in mice.
AB  - The availability of genetically manipulated mice offers a golden opportunity for
      the study of the contribution of the genome to diseases. Because of the technical
      difficulty in performing spinal subarachnoid catheterization in mice, this
      opportunity has hitherto been less harnessed in investigations on the role of the
      spinal cord in the physiological or pathological processes. Even less explored
      are spinal mechanisms that underlie cardiovascular regulation since subarachnoid
      catheterization of the mouse thoracic spinal cord, where preganglionic
      sympathetic neurons governing vasomotor tone are located posts the highest
      challenge because of the restricted operating area. We report a procedure for
      subarachnoid catheterization of the thoracic spinal cord in mice that did not
      require laminectomy or drilling of the lamina proper, and compared the
      suitability of two candidate catheters, polyethylene PE-5 catheter (0.51mm, OD)
      and polyurethane PU-10 catheter (0.25mm, OD). Whereas all implanted mice resumed
      normal feeding one day after surgery and were devoid of bladder dysfunction or
      self-mutilation, the smaller and softer PU-10 catheter compared favorably because
      of lower post-operative mortality rate and no unilateral lower limb paresis.

PMID- 21723323
TI  - 4D in in vivo 2-photon laser scanning fluorescence microscopy with sample motion
      in 6 degrees of freedom.
AB  - 2-Photon laser scanning microscopy (TPLSM) is often used for chronic in vivo
      studies. Small deviations in the sample orientation, however, make comparison of
      three-dimensional image stacks taken at different time-points challenging. When
      analysing changes of three-dimensional structures over time (4D imaging) this
      fundamental problem is one of the main limitations when complex structures are
      studied repetitively. We used an upright two-photon microscope complemented with
      a software-controlled stage-rotation instead of a conventional stage for chronic
      in vivo imaging in the brain of transgenic mouse models of Alzheimer's disease.
      Before every session an optimal imaging condition was successfully created by
      aligning the surface of the cranial window perfectly perpendicular to the laser
      beam. Deviations in the sample orientation between consecutive imaging sessions
      could be eliminated which improves conditions for chronic in vivo studies.

PMID- 21723324
TI  - IL-15 and dendritic cells induce proliferation of CD4+CD25+ regulatory T cells
      from peripheral blood.
AB  - CD4(+)CD25(+) regulatory T cells (Tregs) have recently been the subject of
      intense research due to their strong immunosuppressive effect. Increasing
      evidence suggests that IL-15 plays an important role in Tregs biology.
      Nevertheless, the mechanism by which IL-15 performs this function remains to be
      fully elucidated. To address this question, we isolated Tregs from human
      peripheral blood, and utilized IL-15, dendritic cells (DCs), or DCs combined with
      IL-15, to examine the proliferation of Tregs and to explore related molecular
      mechanisms. Here, we show that IL-15 can induce the proliferation of Tregs in the
      presence of DCs. The induction is mediated by DCs presenting IL-15 in trans to
      Tregs. Simultaneously, DCs-derived IL-2, regulated by IL-15, may also play a
      supportive role. After IL-15 withdrawal, IL-15 trans-endosomal recycling in DCs
      contributes to the proliferation of Tregs. The activation of Akt, Erk1/2 and
      STAT(5), and the degradation of p27(kip1) may be involved in this process. These
      findings might explain the proliferation of Tregs in the absence of IL-2 in vivo
      and provide a novel method to achieve large-scale proliferation of Tregs in vitro
      in order to obtain cell numbers sufficient for immunotherapy.

PMID- 21723325
TI  - Development and validation of a hepatitis B virus DNA sequencing assay for
      assessment of antiviral resistance, viral genotype and surface antigen mutation
      status.
AB  - The objective of this study was to develop a DNA sequencing assay that examines
      sensitively and reliably all conserved domains of the reverse transcriptase
      encoding region of the HBV genome for antiviral resistance-associated mutations
      while simultaneously producing ample information for precise genotyping and
      determination of HBsAg mutation. This assay was used to examine 1000 de
      identified HBV DNA positive samples with known viral loads from a broad-based,
      unselected patient population from across the United States. Of these, 946 were
      assayed successfully. Antiviral resistance-associated mutations were identified
      in 104 samples. The escape mutation sG145R in the surface antigen was identified
      in 0.8% of patient samples. Infections with genotypes A, B, C, D, E, F, G and H
      were observed in 36.6%, 19.6%, 21.7%, 13.5%, 3.6%, 0.7%, 2.2%, and 0.5% of
      patient samples respectively. Fifteen samples (1.6%) appeared to harbor
      infections with multiple genotypes as shown by the presence of double peaks
      throughout sequence electropherograms. The limit of detection of this assay was
      approximately 150IU/mL.

PMID- 21723326
TI  - A precise excision of the complete Epstein-Barr virus genome in a plasmid based
      on a bacterial artificial chromosome.
AB  - The Maxi-EBV is a bacterial artificial chromosome (BAC)-based plasmid that
      contains the complete Epstein-Barr virus (EBV) genome of 172 kb. This plasmid
      also carries an additional cassette of 11.5 kb in size for the expression of a
      mini F factor, selection markers and GFP. In the intracellular study of EBV
      infection based on the Maxi-EBV system, a parallel control that only contains
      this 11.5 kb vector is desirable but unavailable. In order to construct the
      vector in this approach, a clean deletion of the complete EBV genome from the
      Maxi-EBV was performed. This was achieved by homologous recombination using the
      bacteriophage lambda Red system. Initially, an FRT-flanked kanamycin-resistance
      (kan) fragment of 1.4 kb with 61 bp homologies on the ends was introduced into
      the Maxi-EBV plasmid, replacing the 172-kb EBV genome. The kan gene was then
      removed by Flp/FRT excision. The results of identification demonstrated that the
      mutation was generated precisely. The results highlight the feasibility for a
      genome as large as 172 kb to be replaced by a greatly shorter fragment and for a
      much smaller vector backbone to be retrieved. Cell lines derived from the
      transfection of the vector will subsequently be appropriate controls in the
      related study.

PMID- 21723327
TI  - Behavioural and neuronal activation after microinjections of AMPA and NMDA into
      the perifornical lateral hypothalamus in rats.
AB  - The perifornical lateral hypothalamic area (PeFLH), which houses
      orexin/hypocretin (OX) neurons, is thought to play an important role in arousal,
      feeding, and locomotor activity. The present study examined behavioural effects
      of activating PeFLH neurons with microinjections of ionotropic glutamate receptor
      agonists. Three separate unilateral microinjections of either (1) AMPA (1 and 2mM
      in 0.1 MUL artificial cerebrospinal fluid, ACSF) and ACSF, or (2) NMDA (1 and
      10mM in 0.1 MUL ACSF), and ACSF were made into the PeFLH of adult male rats.
      Following each injection, the rats were placed into an open field for behavioural
      scoring for 45 min. Rats were perfused after the third injection for
      immunohistochemistry for c-Fos and OX to assess the level of activation of OX
      neurons. Behavioural analyses showed that, as compared to ACSF conditions, AMPA
      injections produced a dose-dependent increase in locomotion and rearing that
      persisted throughout the 45 min recording period, and an increase in drinking.
      Injection of NMDA at 10mM, but not 1mM, induced a transient increase in
      locomotion and an increase in feeding. Histological analyses showed that while
      both agonists increased the number of neurons immunoreactive for c-Fos in the
      PeFLH, only AMPA increased the number of neurons immunoreactive for both c-Fos
      and OX. There were positive correlations between the number of c-Fos/OX
      immunoreactive neurons and the amounts of locomotion, rearing, and drinking.
      These results support the role of ionotropic glutamate receptors on OX and other
      neurons in the PeFLH in the regulation of locomotor and ingestive behaviours.

PMID- 21723328
TI  - Cross-modal versus within-modal recall: differences in behavioral and brain
      responses.
AB  - Although human experience is multisensory in nature, previous research has
      focused predominantly on memory for unisensory as opposed to multisensory
      information. In this work, we sought to investigate behavioral and neural
      differences between the cued recall of cross-modal audiovisual associations
      versus within-modal visual or auditory associations. Participants were presented
      with cue-target associations comprised of pairs of nonsense objects, pairs of
      nonsense sounds, objects paired with sounds, and sounds paired with objects.
      Subsequently, they were required to recall the modality of the target given the
      cue while behavioral accuracy, reaction time, and blood oxygenation level
      dependent (BOLD) activation were measured. Successful within-modal recall was
      associated with modality-specific reactivation in primary perceptual regions, and
      was more accurate than cross-modal retrieval. When auditory targets were
      correctly or incorrectly recalled using a cross-modal visual cue, there was re
      activation in auditory association cortex, and recall of information from cross
      modal associations activated the hippocampus to a greater degree than within
      modal associations. Findings support theories that propose an overlap between
      regions active during perception and memory, and show that behavioral and neural
      differences exist between within- and cross-modal associations. Overall the
      current study highlights the importance of the role of multisensory information
      in memory.

PMID- 21723329
TI  - Oxidative stress protection of Trypanosomes requires selenophosphate synthase.
AB  - Selenoproteins are characterized by the incorporation of at least one amino acid
      selenocysteine (Sec-U) encoded by in-frame UGA stop codons. These proteins, as
      well as the components of the Sec synthesis pathway, are present in members of
      the bacteria, archaea and eukaryote domains. Although not a ubiquitous pathway in
      all organisms, it was also identified in several protozoa, including the
      Kinetoplastida. Genetic evidence has indicated that the pathway is non-essential
      to the survival of Trypanosoma growing in non-stressed conditions. By analyzing
      the effects of RNA interference of the Trypanosoma brucei selenophosphate
      synthetase SPS2, we found a requirement under sub-optimal growth conditions. The
      present work shows that SPS2 is involved in oxidative stress protection of the
      parasite and its absence severely hampers the parasite survival in the presence
      of an oxidizing environment that results in an apoptotic-like phenotype and cell
      death.

PMID- 21723330
TI  - Transgenesis in the parasitic nematode Strongyloides ratti.
AB  - Strongyloides and related genera are advantageous subjects for transgenesis in
      parasitic nematodes, primarily by gonadal microinjection as has been used with
      Caenorhabditis elegans. Transgenesis has been achieved in Strongyloides
      stercoralis and in Parastrongyloides trichosuri, but both of these lack well
      adapted, conventional laboratory hosts in which to derive transgenic lines. By
      contrast, Strongyloides ratti develops in laboratory rats with high efficiency
      and offers the added advantages of robust genomic and transcriptomic databases
      and substantial volumes of genetic, developmental and immunological data.
      Therefore, we evaluated methodology for transgenesis in S. stercoralis as a means
      of transforming S. ratti. S. stercoralis-based GFP reporter constructs were
      expressed in a proportion of F1 transgenic S. ratti following gonadal
      microinjection into parental free-living females. Frequencies of transgene
      expression in S. ratti, ranged from 3.7% for pAJ09 to 6.8% for pAJ20; respective
      frequencies for these constructs in S. stercoralis were 5.6% and 33.5%.
      Anatomical patterns of transgene expression were virtually identical in S. ratti
      and S. stercoralis. This is the first report of transgenesis in S. ratti, an
      important model organism for biological investigations of parasitic nematodes.
      Availability of the rat as a well-adapted laboratory host will facilitate
      derivation of transgenic lines of this parasite.

PMID- 21723331
TI  - Underestimation of cardiac vagal control in regular exercisers by 24-hour heart
      rate variability recordings.
AB  - OBJECTIVE: To examine whether ceiling effects at long inter beat intervals
      (IBIs)cause an underestimation of cardiac vagal control in regular exercisers by
      time and frequency-domain measures of respiratory sinus arrhythmia (RSA).
      METHODS: 24-hour ECG and respiration recordings were performed in 26 regularly
      exercising subjects, actively engaged in aerobic training for the past year, and
      enrolled in supervised training in the six weeks pre-study, and in 26 age- and
      sex-matched non-exercisers. Sleep and waking levels of cardiac vagal control were
      estimated by RSA obtained through the peak-valley method, by the standard
      deviation of the IBIs, the root mean square of successive IBIs, and the high
      frequency IBI spectral power. RESULTS: In 11 of the exercisers the IBI-RSA
      relationship was characterized by a quadratic relationship. This reflected a
      ceiling effect at very long IBI values attained by regular exercisers,
      particularly during the nighttime recording. Irrespective of this ceiling effect,
      RSA as well as other heart rate variability (HRV) measures was still
      significantly larger in the exercisers with a quadratic IBI-RSA relationship than
      in non-exercisers or exercisers with a linear IBI-RSA relationship. CONCLUSIONS:
      We conclude that a subgroup of regular exercisers is characterized by a low heart
      rate paired to high levels of cardiac vagal control. In these exercisers, vagal
      control is underestimated from HRV measures in ambulatory recordings. Inspection
      of the IBI-RSA relationship should be routinely added when HRV measures are used
      to index cardiac vagal control.

PMID- 21723332
TI  - Quantification of metabolic limitations during recombinant protein production in
      Escherichia coli.
AB  - Escherichia coli is one of the major microorganisms for recombinant protein
      production because it has been best characterized in terms of molecular genetics
      and physiology, and because of the availability of various expression vectors and
      strains. The synthesis of proteins is one of the most energy consuming processes
      in the cell, with the result that cellular energy supply may become critical.
      Indeed, the so called metabolic burden of recombinant protein synthesis was
      reported to cause alterations in the operation of the host's central carbon
      metabolism. To quantify these alterations in E. coli metabolism in dependence of
      the rate of recombinant protein production, (13)C-tracer-based metabolic flux
      analysis in differently induced cultures was used. To avoid dilution of the (13)C
      tracer signal by the culture history, the recombinant protein produced was used
      as a flux probe, i.e., as a read out of intracellular flux distributions. In
      detail, an increase in the generation rate rising from 36 mmol(ATP)g(CDW)(-1)h(
      1) for the reference strain to 45 mmol(ATP)g(CDW)(-1)h(-1) for the highest
      yielding strain was observed during batch cultivation. Notably, the flux through
      the TCA cycle was rather constant at 2.5+/-0.1 mmol g(CDW)(-1)h(-1), hence was
      independent of the induced strength for gene expression. E. coli compensated for
      the additional energy demand of recombinant protein synthesis by reducing the
      biomass formation to almost 60%, resulting in excess NADPH. Speculative, this
      excess NADPH was converted to NADH via the soluble transhydrogenase and
      subsequently used for ATP generation in the electron transport chain. In this
      study, the metabolic burden was quantified by the biomass yield on ATP, which
      constantly decreased from 11.7g(CDW)mmol(ATP)(-1) for the reference strain to
      4.9g(CDW)mmol(ATP)(-1) for the highest yielding strain. The insights into the
      operation of the metabolism of E. coli during recombinant protein production
      might guide the optimization of microbial hosts and fermentation conditions.

PMID- 21723333
TI  - Improved thermostability and PCR efficiency of Thermococcus celericrescens DNA
      polymerase via site-directed mutagenesis.
AB  - The Thermococcus celericrescens (Tcel) DNA polymerase gene, which contains a 2328
      bp open reading frame that encodes 775 amino acid residues, was expressed in the
      Escherichia coli strain Rosetta(DE3)pLysS. The expressed enzyme was purified
      through heat treatment, HisTrapTM HP column chromatography and then HiTrapTM SP
      HP column chromatography. Tcel DNA polymerase has poor thermostability and PCR
      efficiency compared to those of other family B DNA polymerases. To improve
      thermostability and PCR efficiency, mutant Tcel DNA polymerases were created via
      site-directed mutagenesis. Specifically, we targeted the A752 residue for
      enhanced thermostability and the N213 residue for improved PCR efficiency. The
      mutant Tcel DNA polymerases all showed enhanced PCR efficiency and
      thermostability compared to those of the wild-type Tcel DNA polymerase.
      Specifically, the double mutant TcelA752K/N213D DNA polymerase had an
      approximately three-fold increase in thermostability over that of the wild-type
      enzyme and amplified a long 10-kb PCR product in an extension time of 2min.
      However, there was a small change in the 3'->5' exonuclease activity compared
      with that of the wild-type Tcel DNA polymerase, even though the mutation is in
      the ExoII motif. The double mutant TcelA752K/N213D DNA polymerase had a 2.6-fold
      lower error rate compared to that of Taq DNA polymerase. It seems that the double
      mutant TcelA752K/N213D DNA polymerase can be used in LA (long and accurate) PCR.

PMID- 21723334
TI  - Agricultural biotechnologies in developing countries and their possible
      contribution to food security.
AB  - Latest FAO figures indicate that an estimated 925 million people are
      undernourished in 2010, representing almost 16% of the population in developing
      countries. Looking to the future, there are also major challenges ahead from the
      rapidly changing socio-economic environment (increasing world population and
      urbanisation, and dietary changes) and climate change. Promoting agriculture in
      developing countries is the key to achieving food security, and it is essential
      to act in four ways: to increase investment in agriculture, broaden access to
      food, improve governance of global trade, and increase productivity while
      conserving natural resources. To enable the fourth action, the suite of
      technological options for farmers should be as broad as possible, including
      agricultural biotechnologies. Agricultural biotechnologies represent a broad
      range of technologies used in food and agriculture for the genetic improvement of
      plant varieties and animal populations, characterisation and conservation of
      genetic resources, diagnosis of plant or animal diseases and other purposes.
      Discussions about agricultural biotechnology have been dominated by the
      continuing controversy surrounding genetic modification and its resulting
      products, genetically modified organisms (GMOs). The polarised debate has led to
      non-GMO biotechnologies being overshadowed, often hindering their development and
      application. Extensive documentation from the FAO international technical
      conference on Agricultural Biotechnologies in Developing Countries (ABDC-10),
      that took place in Guadalajara, Mexico, on 1-4 March 2010, gave a very good
      overview of the many ways that different agricultural biotechnologies are being
      used to increase productivity and conserve natural resources in the crop,
      livestock, fishery, forestry and agro-industry sectors in developing countries.
      The conference brought together about 300 policy-makers, scientists and
      representatives of intergovernmental and international non-governmental
      organisations, including delegations from 42 FAO Member States. At the end of
      ABDC-10, the Member States reached a number of key conclusions, agreeing, inter
      alia, that FAO and other relevant international organisations and donors should
      significantly increase their efforts to support the strengthening of national
      capacities in the development and appropriate use of pro-poor agricultural
      biotechnologies.

PMID- 21723335
TI  - Simultaneous saccharification and continuous fermentation of sludge-containing
      mash for bioethanol production by Saccharomyces cerevisiae CHFY0321.
AB  - A continuous process was employed to improve the volumetric productivity of
      bioethanol production from cassava mash containing sludge and to simplify the
      process of ethanol production from cassava. After raw cassava powder was
      liquefied, it was used directly in a continuous process without sludge filtration
      or saccharification. A fermentor consisting of four linked stirrer tanks was used
      for simultaneous saccharification and continuous fermentation (SSCF). Although
      the mash contained sludge, continuous fermentation was successfully achieved. We
      chose the dilution rate on the basis of the maximum saccharification time; the
      highest volumetric productivity and ethanol yield were observed at a dilution
      rate of 0.028 h-1. The volumetric productivity, final ethanol concentration, and
      % of theoretical ethanol yield were 2.41 g/Lh, 86.1g/L, and 91%, respectively.
      This SSCF process using the self-flocculating yeast Saccharomyces cerevisiae
      CHFY0321 illustrates the possibility of realizing cost-effective bioethanol
      production by eliminating additional saccharification and filtration processes.
      In addition, flocculent CHFY0321, which our group developed, showed excellent
      fermentation results under continuous ethanol production.

PMID- 21723336
TI  - Bioconversion of car-3-ene by a dioxygenase of Pleurotus sapidus.
AB  - Mycelium of the basidiomycete Pleurotus sapidus known to contain a novel
      dioxygenase was used for the bioconversion of car-3-ene [I]. After 4h of
      incubation 25.3mgL(-1) car-3-en-5-one [V], 5.4mgL(-1) car-3-en-2-one [VII], and
      7.3mgL(-1) car-2-en-4-one [XV] accumulated as major oxidation products. The
      identity of the respective carenones and their corresponding alcohols was
      confirmed by comparison with MS and NMR spectral data obtained for synthesized
      authentic compounds. The peak areas of oxidation products were at least five
      times higher as compared with autoxidation. A radical mechanism similar to
      lipoxygenase catalysis was proposed and substantiated with detailed product
      analyses. The reduction of assumed car-3-ene hydroperoxides to the corresponding
      alcohols evidenced the radical initiated formation of hydroperoxides and
      confirmed the regio- and stereo-selectivity of the dioxygenase. The introduction
      of molecular oxygen into the bicyclic car-3-ene [I] molecule occurred at allylic
      positions of a cyclic isopentenyl moiety with a pronounced preference for the
      position adjacent to the non-substituted carbon atom of the C-C-double bond. This
      co-factor independent selective oxygenation presents an alternative to P450 mono
      oxygenase based approaches for the production of terpene derived flavor
      compounds, pharmaceuticals and other fine chemicals.

PMID- 21723337
TI  - Heterologous expression of Aspen PTM3, a MADS box gene in cotton.
AB  - The PTM3 gene of Aspen was ectopically expressed in cotton to explore the
      opportunity to introduce desirable agronomic traits with the potential to improve
      yield and modify the duration of the parent cotton variety. Sixty-seven
      transgenic cotton lines expressing Aspen PTM3 (MADS box) gene were developed. The
      transgenic cotton lines expressing PTM3 gene showed earliness of 4-15 days
      variations in flowering and maturity. The transgenic lines were confirmed by
      kanamycin leaf paint assay, GUS assay and PCR. Among 67 transgenic lines, the
      event-10 showed profuse branching, event-24 showed abnormal growth and the
      remaining events exhibited single erect phenotype. In addition, the event-24
      produced no flower and this might be due to the positional effect of PTM3 gene
      integration. Southern blot analysis performed for event-10, 24 and 48 showed
      distinct single copy integrations of PTM3 gene cassette. GUS assay performed
      using various plant parts of event-10 showed constitutive expression of the
      transgene. In view of cotton breeding, among all the events, the event-10 was
      found to be phenotypically significant with earliness of 12 days in flowering and
      15 days in maturity and yield enhancement of 27%. In addition, the event-10
      showed no square dropping and allowed the plants to bear more number of bolls.
      Based on these results, event-10 was chosen to carry out the inheritance study of
      expressed characters in the progeny.

PMID- 21723338
TI  - Development of new positive-selection RIVET tools: detection of induced promoters
      by the excision-based transcriptional activation of an aacCI (GmR)-gfp fusion.
AB  - RIVET (Recombination Based in vivo Expression Technology) is a powerful genetic
      tool originally conceived for the identification of genes induced in complex
      biological niches where conventional transcriptomics is difficult to use. With a
      broader application, genetic recombination-based technologies have also been
      used, in combination with regulatory proteins and specific transcriptional
      regulators, for the development of highly sensitive biosensor systems. RIVET
      systems generally comprise two modules: a promoter-trap cassette generating
      genomic transcriptional fusions to the tnpR gene encoding the Tn-gammadelta TnpR
      resolvase, and a reporter cassette carrying res-flanked selection markers that
      are excised upon expression of tnpR to produce an irreversible, inheritable
      phenotypic change. We report here the construction and validation of a new set of
      positive-selection RIVET systems that, upon induction of the promoter-trap
      module, generate the transcriptional activation of an antibiotic-resistant and a
      green-fluorescent phenotype. Two classes of promoter-trap tools were constructed
      to generate transcriptional fusions to tnpR: one based on the use of a narrow
      host-range plasmid (pRIVET-I), integrative in several Gram-negative bacteria, and
      the other based on the use of a broad-host-range plasmid (pRIVET-R). The system
      was evaluated in the model soil bacterium Sinorhizobium meliloti, where a clear
      cut phenotypic transition from Nm(R)-Gm(S)-GFP(-) to Nm(S)-Gm(R)-GFP(+) occurred
      upon expression of tnpR. A S. meliloti integrative RIVET library was constructed
      in pRIVET-I and, as expected, changes in the extracellular conditions (e.g., salt
      stress) triggered a significant increase in the appearance of Gm(R)-GFP(+)
      (excised) clones. The sacB-independent positive-selection RIVET systems here
      described provide suitable basic tools both for the construction of new
      recombination-based biosensors and for the search of bacterial markers induced
      when microorganisms colonize and invade complex environments and eukaryotic
      hosts.

PMID- 21723339
TI  - Production of 3-hydroxypropionic acid via malonyl-CoA pathway using recombinant
      Escherichia coli strains.
AB  - Malonyl-CoA is an intermediary compound that is produced during fatty acid
      metabolism. Our study aimed to produce the commercially important platform
      chemical 3-hydroxypropionic acid (3-HP) from its immediate precursor malonyl-CoA
      by recombinant Escherichia coli strains heterologously expressing the mcr gene of
      Chloroflexus aurantiacus DSM 635, encoding an NADPH-dependent malonyl-CoA
      reductase (MCR). The recombinant E. coli overexpressing mcr under the T5 promoter
      showed MCR activity of 0.015 U mg-1 protein in crude cell extract and produced
      0.71 mmol/L of 3-HP in 24h in shake flask cultivation under aerobic conditions
      with glucose as the sole source of carbon. When acetyl-CoA carboxylase and
      biotinilase, encoded by the genes accADBCb (ACC) of E. coli K-12 were
      overexpressed along with MCR, the final 3-HP titer improved by 2-fold, which is
      1.6 mM. Additional expression of the gene pntAB, encoding nicotinamide nucleotide
      transhydrogenase that converts NADH to NADPH, increased 3-HP production to 2.14
      mM. The strain was further developed by deleting the sucAB gene, encoding alpha
      ketoglutarate dehydrogenase complex in tricarboxylic acid (TCA) cycle, or
      blocking lactate and acetate production pathways, and evaluated for the
      production of 3-HP. We report on the feasibility of producing 3-HP from glucose
      through the malonyl-CoA pathway.

PMID- 21723340
TI  - Sustained H2 production in a Chlamydomonas reinhardtii D1 protein mutant.
AB  - In the present investigation, a detailed biochemical analysis of the high H2
      producer D1 protein mutant strain L159I-N230Y of Chlamydomonas reinhardtii,
      carrying a double amino acid substitution, was made. The leucine residue L159 was
      replaced by isoleucine, and the N230 asparagine was replaced by tyrosine. The
      performance of this strain was compared to that of the cc124 strain. The mutant
      showed a sustained capacity to donate electrons by means of direct biophotolysis
      for H2 production, as demonstrated by the higher efficiency of utilization of the
      hydrogenase enzyme when carried out under anaerobic conditions. The latter
      property was maintained also under sulfur deprivation. Furthermore, when compared
      to the cc124, the mutant showed a higher amount of D1 protein content, a higher
      carbohydrate storage capacity and a sustained PSII direct contribution to the H2
      production during sulfur deprivation. The addition of DCMU to the cells showed
      that as much as 7.0 mL H2 liter of culture h-1 were produced by means of direct
      biophotolysis. The maximum apparent light-to-hydrogen conversion efficiency
      expressed on PAR (photosynthetically active radiation) reached 3.22%, while PSII
      efficiency to perform direct biophotolysis was calculated to be 2.03%. These
      values are significantly higher than what has been reported in the literature.

PMID- 21723341
TI  - Detection of toxic lignin hydrolysate-related compounds using an inaA::luxCDABE
      fusion strain.
AB  - Real-time quantitative PCR analyses of Escherichia coli str. BL21(DE3) exposed to
      0.5 g/L ferulic and coumaric acid showed that the inaA gene was significantly
      induced (7.7- and 3.6-fold higher, respectively). Consequently, a transcriptional
      fusion of the inaA promoter with the luxCDABE operon was constructed and
      characterized with several compounds identified within hydrolysates. Tests
      demonstrated that the phenolics were major inducers, while acetic acid and
      furfural had only a minor or no effect on the inaA expression respectively.
      Additional tests with mutant E. coli strains found that a marA partially
      abolished the response while a marB knock-out led to a 2-3-fold higher basal
      level expression as evidenced by the bioluminescent levels of the cultures.
      However, a significant induction was seen even in the marA mutant, suggesting
      some other control mechanism is involved in regulating inaA expression during an
      exposure to the hydrolysate compounds. Finally, E. coli str. BL21(DE3)/pSP4 was
      used to analyze a spruce hydrolysate sample. Real-time quantitative PCR showed a
      2.8-fold induction of the inaA expression level while the bioluminescence from
      the exposed culture was 22-fold higher than the control, demonstrating the
      possible application of this reporter strain to analyze hydrolysates for the
      presence of fermentation-inhibiting phenolics.

PMID- 21723342
TI  - Growth factor withdrawal in combination with sodium butyrate addition extends
      culture longevity and enhances antibody production in CHO cells.
AB  - The effect of growth factor (GF) and sodium butyrate (NaBu) on Chinese hamster
      ovary (CHO) cell growth, cell viability and antibody production was investigated
      using shaking flasks in GF-containing and GF-deficient medium containing 0, 1 and
      3mM NaBu. The withdrawal of GF and the addition of NaBu suppressed cell growth,
      but they significantly increased specific antibody productivity, q(Ab).
      Interestingly, the withdrawal of GF in combination with the addition of NaBu
      markedly retarded cell death, leading to extended culture longevity. For
      instance, at 3mM NaBu, cell viability fell below 80% after day 4 in GF-containing
      medium, but it remained over 80% until day 18 in GF-deficient medium. Due to the
      enhanced q(Ab) and the extended culture longevity, approximately 2-fold increase
      in total antibody production was achieved in pseudo-perfusion culture with 1mM
      NaBu in GF-deficient medium, compared to the culture in GF-containing medium. The
      effect of GF and NaBu on the change in the expression and activity of cellular
      proteins, c-Myc, Bcl-2 and pyruvate dehydrogenase (PDH), was also investigated.
      Both the withdrawal of GF and the addition of NaBu decreased the expression of c
      Myc. The expression of Bcl-2 was enhanced by the addition of NaBu in a dose
      dependent manner while it was not affected by the withdrawal of GF. In addition,
      both the withdrawal of GF and the addition of NaBu reduced metabolic rates,
      q(Glc), q(Lac) and Y(Lac/Glc), and increased PDH activity while not affecting PDH
      expression, suggesting that they may reduce the glycolytic rates, but enhance the
      conversion rates of pyruvate to TCA intermediates. Taken together, the withdrawal
      of GF in combination with the addition of NaBu can be considered as a relevant
      strategy for alleviating NaBu-induced cell apoptosis and enhancing antibody
      production since it can be easily implemented as well as enhance q(Ab) and extend
      culture longevity.

PMID- 21723343
TI  - Utility of Aspergillus niger citrate synthase promoter for heterologous
      expression.
AB  - Citrate synthase is a central player in the acidogenic metabolism of Aspergillus
      niger. The 5' upstream sequence (0.9kb DNA) of citrate synthase gene (citA) from
      A. niger NCIM 565 was analyzed and its promoter function demonstrated through the
      heterologous expression of two proteins. The cloned citrate synthase promoter
      (PcitA) sequence was able to express bar coding sequence thereby conferring
      phosphinothricin resistance. This sequence was further analyzed by systematic
      deletions to define an effective but compact functional promoter. The PcitA
      driven egfp expression showed that PcitA was active in all differentiation cell
      stages of A. niger. EGFP expression was highest on non-repressible carbon sources
      like acetate and glycerol. Mycelial EGFP levels increased during acidogenic
      growth suggesting that PcitA is functional throughout this cultivation. A. niger
      PcitA is the first Krebs cycle gene promoter used to express heterologous
      proteins in filamentous fungi.

PMID- 21723344
TI  - Combined influence of fermentation and drying conditions on survival and
      metabolic activity of starter and probiotic cultures after low-temperature vacuum
      drying.
AB  - The influence of low temperature vacuum drying process parameters on the
      survival, metabolic activity and residual water content of three different
      bacterial strains (Lactobacillus paracasei ssp. paracasei, Lactobacillus
      delbrueckii ssp. bulgaricus and Bifidobacterium lactis) was investigated. Shelf
      temperature and chamber pressure were varied and optimized by response surface
      methodology with regard to survival and residual water content. It is shown that
      the survival rate after low temperature vacuum drying is comparable to that of
      freeze drying. Based on the optimization experiments the combined influence of
      fermentation pH and drying process parameters was studied for the most
      detrimental and the best process condition, respectively. The results show that
      interactions between process and fermentation conditions have to be taken in
      account and that these influences are highly strain specific.

PMID- 21723345
TI  - Improved production of monoclonal antibodies through oxygen-limited cultivation
      of glycoengineered yeast.
AB  - Glycoengineering technology can elucidate and exploit glycan related structure
      function relationships for therapeutic proteins. Glycoengineered yeast has been
      established as a safe, robust, scalable, and economically viable expression
      platform. It has been found that specific productivity of antibodies in
      glycoengineered Pichia pastoris is a non-linear function of specific growth rate
      that is dictated by a limited methanol feed rate. The optimal carbon-limited
      cultivation requires an exponential methanol feed rate with an increasing biomass
      concentration and more significantly an increase in heat and mass transfer
      requirements that often become the limiting factor in scale-up. Both heat and
      mass transfer are stoichiometrically linked to the oxygen uptake rate.
      Consequently an oxygen-limited cultivation approach was evaluated to limit the
      oxygen uptake rate and ensure robust and reliable scale-up. The oxygen-limited
      process not only limited the maximum oxygen uptake rate (and consequently the
      required heat removal rate) in mut+ P. pastoris strains but also enabled
      extension of the induction phase leading to an increased antibody concentration
      (1.9gL(-1) vs. 1.2gL(-1)), improved N-glycan composition and galactosylation, and
      reduced antibody fragmentation. Furthermore, the oxygen-limited process was
      successfully scaled to manufacturing pilot scale and thus presents a promising
      process option for the glycoengineered yeast protein expression platform.

PMID- 21723346
TI  - Substrate complexation and aggregation influence the cyclodextrin
      glycosyltransferase (CGTase) catalyzed synthesis of alkyl glycosides.
AB  - Bacillus macerans cyclodextrin glycosyltransferase (CGTase) was used to convert
      dodecyl-beta-maltoside (DDM) to dodecyl-beta-maltooctaoside (DDMO) using alpha
      cyclodextrin (alpha-CD) or starch as glycosyl donors. At 300mM alpha-CD, varied
      DDM concentration and 60 degrees C, the reaction obeyed Michaelis-Menten kinetics
      with a K(m) value of 18mM and a V(max) value of 100U/mg enzyme. However, at 25mM
      alpha-CD the reaction rate decreased with increasing DDM concentration (5-50mM),
      and when the alpha-CD concentration was varied at fixed DDM concentration an S
      shaped curve was obtained. The deviations from Michaelis-Menten kinetics were
      interpreted as being caused by formation of inclusion complexes between alpha-CD
      and DDM and by micellation of DDM. To achieve a high reaction rate, a high
      concentration of free alpha-CD is necessary, since alpha-CD in the form of a
      complex has low reactivity. When starch is used as glycosyl donor in the CGTase
      catalyzed alkyl glycoside elongation reaction, it is thus important to choose
      reaction conditions under which the cyclization of starch to alpha-CD is
      efficient.

PMID- 21723347
TI  - Epstein-Barr virus genome polymorphisms of Epstein-Barr virus-associated gastric
      carcinoma in gastric remnant carcinoma in Guangzhou, southern China, an endemic
      area of nasopharyngeal carcinoma.
AB  - Epstein-Barr virus (EBV) is associated with a subset of gastric carcinoma which
      was defined as EBV-associated gastric carcinoma (EBVaGC). The proportion of
      EBVaGC in gastric remnant carcinoma (GRC) was apparently higher than that in
      conventional gastric carcinoma (CGC) which occurs in the intact stomach. To
      clarify the possible mechanisms, 26 GRC cases from Guangzhou were investigated
      for the presence of EBV, and the EBV genome polymorphisms of EBVaGC in GRC were
      analyzed. Besides, the clinicopathologic characteristics, EBV latency pattern of
      EBVaGC in GRC were also investigated. Eight (30.8%) out of 26 cases were
      identified as EBVaGCs. Type A strain, prototype F, type I, mut-W1/I1, XhoI- and
      del-LMP1 variants were predominant among EBVaGC patients, accounting for 7
      (87.5%), 7 (87.5%), 8 (100%), 6 (75%), 5 (62.5%) and 8 (100%) cases,
      respectively. All EBVaGC cases were male and with the histology of diffuse-type
      carcinoma. The tumor cells expressed EBNA1 (87.5%) and LMP2A (62.5%) but not
      LMP1, EBNA2 and ZEBRA. Thus, the EBV latency pattern was latency I. These were
      similar to those in CGC, except for the significantly higher proportion of EBVaGC
      in GRC than in CGC, suggesting that there is no more aggressive EBV variant in
      EBVaGC in GRC, and the injuries of gastric mucosa and/or changes of the
      microenvironment within the remnant stomach may be involved in the development of
      EBVaGC in GRC. This, to our knowledge, is the first study concerning about the
      EBV genome polymorphisms of EBVaGC in GRC in the world.

PMID- 21723348
TI  - Additional random, single to multiple genome fragments of Penaeus stylirostris
      densovirus in the giant tiger shrimp genome have implications for viral disease
      diagnosis.
AB  - Scattered reports of viral inserts in shrimp and insect genomes led to the
      hypothesis that random, autonomous insertion of such sequences occurs in these
      organisms and leads to specific, heritable immunity. To test the prediction
      regarding random insertion of viral sequences into the shrimp genome, we examined
      the giant tiger shrimp for random genomic insertions of Penaeus stylirostris
      densovirus (also called IHHNV). By PCR analysis using a set of 7 overlapping
      primer pairs to cover the whole IHHNV genome (4 kb), PCR failure with some pairs
      indicated sequence gaps that revealed a random pattern of putative viral inserts
      in the genomes of individual shrimp. Targeting a putative insert from one
      arbitrarily selected specimen, we used genome walking to reveal a viral insert
      linked to a host microsattelite-like fragment. This differed from 2 previously
      reported inserted fragments of IHHNV in P. monodon. In one specimen, 2 slightly
      different inserts were revealed, probably on paired chromosomes. By design and
      use of chimeric shrimp/virus primer pairs we proved that similar insertions
      occurred in several shrimp specimens, including those infected with IHHNV but
      showing no signs of disease. For the infected specimens, the inserts gave false
      positive PCR test results using 309F/R primers and a new IQ2000 test protocol
      currently recommended for detection of infectious IHHNV. This is the first
      experimental support for the hypothesis-based prediction that a random number and
      length of sequence fragments from a single virus genome may occur in the shrimp
      genome. Since some inserts can give false positive results for infectious IHHNV
      with the recommended methods above, they may have a negative effect on
      international seafood trade. In addition, discard of domesticated shrimp breeding
      stocks based on such false positive results might have negative consequences, if
      such inserts are related to shrimp viral disease tolerance, as also hypothesized.

PMID- 21723349
TI  - Isolation and characterization of cytotoxic cyclotides from Viola philippica.
AB  - Cyclotides are a large family of plant peptides characterized by a macrocyclic
      backbone and knotted arrangement of three disulfide bonds. This unique structure
      renders cyclotides exceptionally stable to thermal, chemical and enzymatic
      treatments. They exhibit a variety of bioactivities, including uterotonic, anti
      HIV, cytotoxic and hemolytic activity and it is these properties that make
      cyclotides an interesting peptide scaffold for drug design. In this study, eight
      new cyclotides (Viphi A-H), along with eight known cyclotides, were isolated from
      Viola philippica, a plant from the Violaceae family. In addition, Viba 17 and
      Mram 8 were isolated for the first time as peptides. The sequences of these
      cyclotides were elucidated primarily by using a strategy involving reduction,
      enzymatic digestion and tandem mass spectroscopy sequencing. Several of the
      cyclotides showed cytotoxic activities against the cancer cell lines MM96L, HeLa
      and BGC-823. The novel cyclotides reported here: (1) enhance the known sequence
      variation observed for cyclotides; (2) extend the number of species known to
      contain cyclotides; (3) provide interesting structure-activity relationships that
      delineate residues important for cytotoxic activity. In addition, this study
      provides insights into the potential active ingredients of traditional Chinese
      medicines.

PMID- 21723350
TI  - Expression of C-type natriuretic peptide and its receptor NPR-B in
      cardiomyocytes.
AB  - C-type natriuretic peptide (CNP) was recently found in myocardium at the mRNA and
      protein levels, but it is not known whether cardiomyocytes are able to produce
      CNP. The aim of this study was to determine the expression of CNP and its
      specific receptor NPR-B in cardiac cells, both in vitro and ex vivo. CNP, brain
      natriuretic peptide (BNP) and natriuretic peptide receptor (NPR)-B mRNA
      expression were examined by RT-PCR in the H9c2 rat cardiac myoblast cell line, in
      neonatal rat primary cardiomyocytes and in human umbilical vein endothelial cells
      (HUVECs) as control. CNP protein expression was probed in cardiac tissue sections
      obtained from adult male minipigs by immunohistochemistry, and in H9c2 cells both
      by immunocytochemistry and by specific radioimmunoassay. The results showed that
      cardiac cells as well as endothelial cells were able to produce CNP. Unlike
      cardiomyocytes, as expected, in endothelial cells expression of BNP was not
      detected. NPR-B mRNA expression was found in both cell types. Production of CNP
      in the heart muscle cells at protein level was confirmed by radioimmunological
      determination (H9c2: CNP=0.86 +/- 0.083 pg/mg) and by immunocytochemistry
      studies. By immunostaining of tissue sections, CNP was detected in both
      endothelium and cardiomyocytes. Expression of CNP in cardiac cells at gene and
      protein levels suggests that the heart is actively involved in the production of
      CNP.

PMID- 21723351
TI  - Toward understanding the role of leptin and leptin receptor antagonism in
      preclinical models of rheumatoid arthritis.
AB  - A potential link between obesity, circulating leptin levels and autoimmune
      disease symptoms suggests that targeting the leptin receptor (ObR) might be a
      viable novel strategy to combat rheumatoid arthritis (RA). However, studies in
      animal models and evaluation of clinical cases did not provide clear view on
      leptin's involvement in RA. To validate ObR as RA target, we used our peptide
      based ObR agonists and antagonist in different in vitro and in vivo models of the
      disease. In human peripheral blood mononuclear cells, leptin and its agonist
      fragment, desI(2)-E1/Aca, moderately induced constitutive activation of a major
      proinflammatory transcription factor, NF-kappaB, while the ObR antagonist peptide
      Allo-aca inhibited the process. Leptin administration itself did not induce
      arthritis in rats, but worsened the clinical condition of mice given K/BxN serum
      transfer arthritis. Simultaneous administration of Allo-aca reduced leptin
      dependent increase in disease severity by more than 50%, but the antagonist was
      ineffective when injected with a 3-day delay. In rats inflicted with mild
      adjuvant-induced arthritis, both leptin and Allo-aca reduced the extent of joint
      swelling and the number of arthritic joints. In a more aggressive disease stage,
      Allo-aca decreased the number of arthritic joints in a dose-dependent manner but
      did not affect other arthritis markers. In summary, leptin exerts diverse effects
      on RA depending on the experimental model. This might reflect the heterogeneous
      character of RA, which is differently impacted by leptin and is unmasked by ObR
      antagonism. Nevertheless, the results suggest that ObR antagonists might become
      useful therapeutics in leptin-sensitive early stages of RA.

PMID- 21723352
TI  - Ethical issues in preventing mother-to-child transmission of hepatitis B by
      immunisation.
AB  - Without intervention, a pregnant woman who is a chronic hepatitis B carrier is at
      risk of transmitting hepatitis B and of her infant becoming a chronic carrier and
      having a significantly increased lifetime risk of developing liver cancer or
      cirrhosis. Hepatitis B vaccine and immunoglobulin reduce the risk of the baby
      becoming a carrier, but with only a short window period after birth to deliver
      this potentially life-saving intervention. We reviewed the evidence on the
      magnitude of the risk. If the carrier mother is e antigen positive (highly
      infective), the calculated risk to the infant without intervention is 75.2%,
      reduced to 6.0% by giving vaccine and immunoglobulin at birth. If the mother is
      surface antigen positive but e antigen negative, the risk to the infant without
      intervention is 10.3%, reduced to 1.0% by giving vaccine and immunoglobulin. If
      vaccine is accepted but immunoglobulin refused, as for example by some Jehovah's
      Witnesses, the risk to babies of e antigen positive mothers is reduced to 21.0%
      and to babies of e antigen negative mothers to 2.6%. These figures can be used to
      inform parents and as a possible basis for child protection proceedings if
      parents decline vaccine and/or immunoglobulin. We argue from the perspective of
      the best interests of the child that the severity of the condition justifies
      initiating child protection proceedings whenever a baby is born to a hepatitis B
      carrier mother and, despite concerted attempts to persuade them, the parents
      refuse vaccine and/or immunoglobulin.

PMID- 21723353
TI  - Correlation of protection against Japanese encephalitis virus and JE vaccine
      (IXIARO((r))) induced neutralizing antibody titers.
AB  - Immune sera from volunteers vaccinated in a blinded Phase 3 clinical trial with
      JE-VAX((r)) and a new Japanese encephalitis virus (JEV) vaccine (IC51 or IXIARO),
      were tested for the ability to protect mice against lethal JEV challenge. Sera
      from IXIARO vaccinated subjects were pooled into four batches based on
      neutralizing antibody measured by plaque reduction neutralization test (PRNT(50)
      titer): high (~200), medium (~40-50), low (~20) and negative (<10). Pooled sera
      from JE-VAX((r)) vaccinated subjects (PRNT(50) titer~55) and pooled JEV antibody
      negative pre-vaccination sera were used as controls. Groups of ten 6- to 7-week
      old female ICR mice were injected intraperitoneally with 0.5 ml of each serum
      pool diluted 1:2 or 1:10, challenged approximately 18 h later with a lethal dose
      of either JEV strain SA14 (genotype III) or strain KE-093 (genotype I) and
      observed for 21 days. All mice in the non-immune serum groups developed clinical
      signs consistent with JEV infection or died, whereas high titer sera from both
      IXIARO and JE-VAX((r)) sera protected 90-100% of the animals. Statistical tests
      showed similar protection against both JEV strains SA14 and KE-093 and protection
      correlated with the anti-JEV antibody titer of IXIARO sera as measured by
      PRNT(50). Ex vivo neutralizing antibody titers showed that almost all mice with a
      titer of 10 or greater were fully protected. In a separate study, analysis of
      geometric mean titers (GMTs) of the groups of mice vaccinated with different
      doses of IXIARO and challenged with JEV SA14 provided additional evidence that
      titers>=10 were protective.

PMID- 21723354
TI  - Influenza virus-like particle can accommodate multiple subtypes of hemagglutinin
      and protect from multiple influenza types and subtypes.
AB  - Despite existing vaccines and specific therapies, epidemics of seasonal influenza
      annually claim 200,000-500,000 lives worldwide. Pandemic influenza represents an
      even greater threat, with numerous potentially pandemic viruses circulating in
      nature. Development of multi-specific vaccines against multiple pandemic or
      seasonal strains is important for human health and the global economy. Here we
      report a novel virus-like particle (VLP) platform that contains three
      hemagglutinin (HA) subtypes. This recombinant vaccine design resulted in the
      expression of three HA subtypes co-localized within a VLP. Experimental triple-HA
      VLPs containing HA proteins derived from H5N1, H7N2, and H2N3 viruses were
      immunogenic and protected ferrets from challenge from all three potentially
      pandemic viruses. Similarly, VLPs containing HA subtypes derived from seasonal
      H1N1, H3N2, and type B influenza viruses protected ferrets from three seasonal
      influenza viruses. We conclude that this technology may represent a novel
      strategy for rapid development of trivalent seasonal and pandemic vaccines.

PMID- 21723355
TI  - An alternative renewable source of squalene for use in emulsion adjuvants.
AB  - Emulsions have been used to boost immunogenicity of antigens since the discovery
      of complete Freunds adjuvant. Optimization to reduce reactogenicity of emulsion
      adjuvants lead to the development of oil in water emulsions based on squalene.
      MF59 is an oil-in-water emulsion that is a component of an approved influenza
      product in Europe. Currently MF59 is manufactured from squalene derived from an
      animal source. Recently a high purity plant-derived squalene source has become
      available at an appropriate purity for a vaccine adjuvant. The purpose of this
      study was to evaluate and compare animal-derived squalene and plant-derived
      squalene for equivalency. Nanoemulsions were prepared and analyzed for size and
      viscosity prepared from each source. The two emulsions were administered in two
      separate animal studies, one focusing on Neisseria meningitidis B, and one
      focusing on influenza. Readouts were ELISA titers for each antigen and serum
      bactericidal activity for N. meningitidis B, and hemagglutinin inhibition for
      influenza to see the functionality of the antibodies produced. Results indicate
      that there are no differences between the antibodies elicited after immunization
      from an emulsion made with oil derived from either an animal or plant-source.

PMID- 21723356
TI  - Use of the state immunization information system to assess rotavirus vaccine
      effectiveness in Connecticut, 2006-2008.
AB  - Immunization information systems (IIS) contain individual vaccination records and
      have potential use for evaluating post-licensure vaccine effectiveness (VE). A
      matched case-control study was performed by using the Connecticut state IIS to
      calculate rotavirus VE against hospitalization; results were compared with pre
      licensure efficacy and with estimates previously obtained by traditional case
      control methods using matched controls from medical sources and medical chart
      abstracted data. Case-patients (n=54) were vaccine-eligible children with IIS
      entry and hospitalized for rotavirus gastroenteritis during July 2006-December
      2008; each was matched to five control subjects (n=270) who were randomly
      selected from IIS based on case-patient's birth date and town of residence. VE of
      at least one dose was 90.6%, comparable to the pre-licensure efficacy of 96% and
      to the unadjusted 83.5-90.7% estimates by using traditional case-control methods.
      IIS can be a convenient and potentially accurate tool for calculating VE.

PMID- 21723357
TI  - Current trend of pneumococcal serotypes distribution and antibiotic
      susceptibility pattern in Malaysian hospitals.
AB  - From January 2008 to December 2009, 433 Streptococcus pneumoniae strains were
      examined to determine the serotype distribution and susceptibility to selected
      antibiotics. About 50% of them were invasive isolates. The strains were isolated
      from patients of all age groups and 33.55% were isolated from children below 5
      years. The majority was isolated from blood (48.53%) and other sterile specimens
      (6.30%). Community acquired pneumonia (41.70%) is the most common diagnosis
      followed by sepsis (9.54%). Serotyping was done using Pneumotest Plus-Kit and
      antibiotic susceptibility pattern was determined by modified Kirby-Bauer disk
      diffusion method and measurement of minimum inhibitory concentration (MIC) using
      E-test strip. Ten most common serotypes were 19F (15.02%), 6B (10.62%), 19A
      (6.93%), 14 (6.70%), 1 (5.08%), 6A (5.08%), 23F (4.85%), 18C (3.93%), 3 (2.08%)
      and 5 (1.85%). Penicillin MIC ranged between <= 0.012-4 MUg/ml with MIC90 of 1
      MUg/ml. Penicillin resistant rate is 31.78%. The majority of penicillin less
      susceptible strains belonged to serotype 19F followed by 19A and 6B. Based on the
      serotypes distribution 22 (44.00%), 28 (56.00%) and 39 (78.00%) of the invasive
      isolates from children <= 2 years were belonged to serotypes included in the
      PCV7, PCV10 and PCV13, respectively.

PMID- 21723358
TI  - Effectiveness of the monovalent influenza A(H1N1)2009 vaccine in Navarre, Spain,
      2009-2010: cohort and case-control study.
AB  - We defined a population-based cohort (596,755 subjects) in Navarre, Spain, using
      electronic records from physicians, to evaluate the effectiveness of the
      monovalent A(H1N1)2009 vaccine in preventing influenza in the 2009-2010 pandemic
      season. During the 9-week period of vaccine availability and circulation of the
      A(H1N1)2009 virus, 4608 cases of medically attended influenza-like illness (MA
      ILI) were registered (46 per 1000 person-years). After adjustment for
      sociodemographic covariables, outpatient visits and major chronic conditions,
      vaccination was associated with a 32% (95% CI: 8-50%) reduction in the overall
      incidence of MA-ILI. In a test negative case-control analysis nested in the
      cohort, swabs from 633 patients were included, and 123 were confirmed for
      A(H1N1)2009 influenza. No confirmed case had received A(H1N1)2009 vaccine versus
      9.6% of controls (p<0.001). The vaccine effectiveness in preventing laboratory
      confirmed influenza was 89% (95% CI: 36-100%) after adjusting for age, health
      care setting, major chronic conditions and period. Pandemic vaccine was effective
      in preventing MA-ILI and confirmed cases of influenza A(H1N1)2009 in the 2009
      2010 season.

PMID- 21723359
TI  - Genetic variation in folate metabolism is not associated with cognitive
      functioning or mood in healthy adults.
AB  - The present study examined the associations between genetic variation in folate
      metabolism on the one hand and cognitive functioning and mood on the other in
      healthy individuals. Two independent population-based samples were used,
      including 777 participants, aged 24-82 years, from the Maastricht Aging Study
      (MAAS); and 818 participants, aged 50-70 years, from the Folic Acid and Carotid
      Intima-Media Thickness (FACIT) study. Thymidylate synthase (TS) 2R->3R and serine
      hydroxymethyltransferase (SHMT1) 1420C->T polymorphisms were determined in both
      populations. In addition, the 5,10-methylenetetrahydrofolate reductase (MTHFR)
      677C->T polymorphism was determined in the MAAS population. Cognitive performance
      was assessed in both populations using a neuropsychological test battery. In the
      MAAS population only, cognitive performance was retested after 12years of follow
      up (n=612), and mood was measured at baseline (n=772) and 12-year follow-up
      (n=565) by means of the depression subscale of the Symptom Checklist 90. We found
      that in both study populations, cognitive performance was not associated with TS
      2R->3R or SHMT1 1420C->T polymorphisms at baseline, after correction for age,
      sex, and level of education. The MTHFR 677C->T polymorphism was not associated
      with cognitive performance in the MAAS population. None of the polymorphisms in
      the MAAS population were related to mood at baseline or over 12 years. In
      conclusion, our findings do not support the involvement of genetic variation in
      folate metabolism in cognitive performance or mood in healthy individuals.

PMID- 21723360
TI  - Infection by mycotoxigenic fungal species and mycotoxin contamination of maize
      grain in Umbria, central Italy.
AB  - Surveys were carried out in 2006 and 2007 in Umbria (central Italy) to evaluate
      the presence of mycotoxigenic fungi and mycotoxins in maize grain sampled at
      harvest. Fusarium spp., were the most abundant species detected in maize kernels,
      followed by Aspergillus species of sections Flavi and Nigri and by Penicillium
      spp. Among Fusarium species, F. verticillioides was the most prevalent species,
      as detected by PCR directly on the kernels and on the fungi isolated from the
      kernels, followed by F. proliferatum and F. subglutinans. Fumonisins were the
      predominant mycotoxins with values, on average, of 4.3 and 5.7 mgkg(-1), in 2006
      and 2007, respectively, with a maximum of 76.3 mgkg(-1) in the second year.
      Deoxynivalenol ranged from 0.2 to 3.98 mgkg(-1) in 2006 (average 1.04 mgkg(-1))
      and from undetectable levels to 14 mgkg(-1) in 2007 (average 0.86 mgkg(-1)).
      Aflatoxins, analyzed only in 2007, averaged 26.3 MUgkg(-1), with a maximum of 820
      MUgkg(-1). Zearalenone content was always very low. Results indicate that EU
      legal limits for these mycotoxins were rarely exceeded with low levels across
      most of the examined area, suggesting that this region could be considered
      suitable for the production of healthy maize.

PMID- 21723361
TI  - Effects of docosahexaenoic acid and methylmercury on child's brain development
      due to consumption of fish by Finnish mother during pregnancy: a probabilistic
      modeling approach.
AB  - Fish contains both beneficial substances e.g. docosahexaenoic acids but also
      harmful compounds e.g. methylmercury. Importantly, the health effects caused by
      these two substances can be evaluated in one common end point, intelligence
      quotient (IQ), providing a more transparent analysis. We estimated health effects
      of maternal fish consumption on child's central nervous system by creating a
      model with three alternative maternal fish consumption scenarios (lean fish,
      fatty fish, and current fish consumption). Additionally, we analyzed impacts of
      both regular fish consumption and extreme fish consumption habits. At the
      individual level, the simulated net effects were small, encompassing a range of
      one IQ point in all scenarios. Fatty fish consumption, however, clearly generated
      a beneficial net IQ effect, and lean fish consumption evoked an adverse net IQ
      effect. In view of the current fish consumption pattern of Finnish mothers the
      benefits and risks seem to more or less compensate each other. This study clearly
      shows the significance of which fish species are consumed during pregnancy and
      lactation, and the results can be generalized to apply to typical western
      population fish consumption habits.

PMID- 21723362
TI  - Results of a 90-day safety assessment study in mice fed a glucan produced by
      Agrobacterium sp. ZX09.
AB  - Salecan is a novel water-soluble glucan produced by Agrobacterium sp. ZX09. It
      has potential application as a food additive with a unique chemical composition
      and excellent physicochemical properties. The objective of this study was to
      investigate the acute and subchronic toxicity of Salecan. The oral LD50 of
      Salecan in ICR mice was greater than 3000 mg/kg body weight. In the subchronic
      study, ICR mice (10/sex/group) were fed diets containing 0%, 1.0%, 2.5% and 5.0%
      of Salecan (weight/weight) for 13 weeks. Based on the results from the subchronic
      study, the overall health, body weight gain, food consumption and clinical
      pathology parameters were comparable between the groups feed Salecan and the
      control. No dose-related effects were observed in the treated animals. The only
      exception was the observation that blood glucose in female mice fed Salecan was
      lower than in the control group. In addition, the fecal matter from Salecan fed
      mice exhibited increased water content versus the control animals. The no
      observed adverse effect level (NOAEL) of 14478 mg/kg body weight/day was
      determined. The results from this study support the conclusion that Salecan is
      non-toxic at the levels tested and does not pose a risk to human health when used
      in food.

PMID- 21723363
TI  - Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen
      (Garcinia mangostana Linn.) on human melanoma cells.
AB  - Mangosteen (Garcinia mangostana Linn.) is a tropical tree from South East Asia
      and its fruit pericarp is a well-known traditional medicine. In this study, the
      cytotoxic effect of three xanthone compounds (alpha-mangostin, gamma-mangostin,
      and 8-deoxygartanin) from mangosteen pericarp was investigated using the human
      melanoma SK-MEL-28 cell line. Significant dose-dependent reduction in % cell
      viability was induced. gamma-Mangostin and 8-deoxygartanine at 5 MUg/ml increased
      the cell cycle arrest in G(1) phase (90% and 92%) compared with untreated cells
      (78%). All compounds induced apoptosis, of the highest being alpha-mangostin at
      7.5 MUg/ml that induced 59.6% early apoptosis, compared to 1.7% in untreated
      cells. The apoptotic effect of alpha-mangostin was via caspase activation and
      disruption of mitochondrial membrane pathways as evidenced by 25-fold increased
      caspase-3 activity and 9-fold decreased mitochondrial membrane potential when
      compared to untreated cells. In conclusion, these xanthones, especially alpha
      mangostin, are potential candidates as anti-melanoma agents.

PMID- 21723364
TI  - Anti-visceral obesity and antioxidant effects of powdered sea buckthorn
      (Hippophae rhamnoides L.) leaf tea in diet-induced obese mice.
AB  - The potential health benefits of tea have long been studied. This study examined
      the role of powdered sea buckthorn leaf tea (SLT) in high-fat diet-induced obese
      mice. The mice were fed two different doses of SLT (1% and 5%, wt/wt) for six
      weeks. SLT suppressed body weight gain in a dose-dependent manner and
      significantly reduced visceral fat, plasma levels of leptin, triglyceride and
      total cholesterol and ALT activity compared with the high-fat-fed control mice.
      SLT also decreased hepatic triglyceride and cholesterol concentrations and lipid
      accumulation, whereas elevated fecal lipid excretion. High-fat feeding resulted
      in simultaneously decreasing hepatic FAS and G6PD activities and increasing PAP,
      beta-oxidation and CPT activities. However, SLT supplementation during high-fat
      feeding led to a significant decrease in PAP, beta-oxidation and CPT activities
      with a simultaneous increase in G6PD activity. The hepatic CYP2E1 activity and
      hepatic and erythrocyte lipid peroxides were significantly lowered with SLT
      supplements. Hepatic and erythrocyte SOD and CAT activities were also increased
      with SLT supplements in a dose-dependent manner, whereas GSH-Px activity was
      increased in erythrocytes only. These results indicate that SLT has potential
      anti-visceral obesity and antioxidant effects mediated by the regulation of lipid
      and antioxidant metabolism in high-fat diet-induced obese mice.

PMID- 21723365
TI  - Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and
      rodent hepatocytes.
AB  - Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are surface active
      fluorochemicals that, due to their exceptional stability to degradation, are
      persistent in the environment. Both PFOA and PFOS are eliminated slowly in
      humans, with geometric mean serum elimination half-lives estimated at 3.5 and 4.8
      years, respectively. The biological activity of PFOA and PFOS in rodents is
      attributed primarily to transactivation of the nuclear receptor peroxisome
      proliferator activated receptor alpha (PPARA), which is an important regulator of
      lipid and carbohydrate metabolism. However, there are significant species
      specific differences in the response to PFOA and PFOS exposure; non-rodent
      species, including humans, are refractory to several but not all of these
      effects. Many of the metabolic effects have been attributed to the activation of
      PPARA; however, recent studies using PPARalpha knockout mice demonstrate residual
      PPARA-independent effects, some of which may involve the activation of alternate
      nuclear receptors, including NR1I2 (PXR), NR1I3 (CAR), NR1H3 (LXRA), and NR1H4
      (FXR). The objective of this investigation was to characterize the activation of
      multiple nuclear receptors and modulation of metabolic pathways associated with
      exposure to PFOA and PFOS, and to compare and contrast the effects between rat
      and human primary liver cells using quantitative reverse transcription PCR (RT
      qPCR). Our results demonstrate that multiple nuclear receptors participate in the
      metabolic response to PFOA and PFOS exposure resulting in a substantial shift
      from carbohydrate metabolism to fatty acid oxidation and hepatic triglyceride
      accumulation in rat liver cells. This shift in intermediary metabolism was more
      pronounced for PFOA than PFOS. Furthermore, while there is some similarity in the
      activation of metabolic pathways between rat and humans, particularly in PPARA
      regulated responses; the changes in primary human cells were more subtle and
      possibly reflect an adaptive metabolic response rather than an overt metabolic
      regulation observed in rodents.

PMID- 21723367
TI  - Role of 10-11bp periodicities of eukaryotic DNA sequence in nucleosome
      positioning.
AB  - 10-11bp repeating patterns of the particular dinucleotides were suggested in
      positioning nucleosomes in eukaryotes. In order to assess the role, the 10-11bp
      periodicities of the dinucleotides were examined both in human well-positioned
      nucleosome DNA sequences and in promoter DNA sequences of eight species. Our
      results indicated that the periodical occurrence of the particular dinucleotides
      correlates to positioning nucleosome. The signals of 10-11bp periodicities are
      more pronounced in the nucleosome DNA sequences than in the linker DNA sequences.
      Near the transcription start site, the signals reveal a similar feature that the
      nucleosome organization exhibits. But, it seems that the species do not share the
      same dinucleotides patterns. Furthermore, the dinucleotides patterns are dominant
      at the specific region of genome, indicating their diverse roles in forming and
      organizing nucleosomes. Moreover, the 10-11bp periodicities signals near the
      translation start negatively correlate with gene expression, demonstrating a
      vital role in transcription regulation. Our study reveals some details about the
      roles of DNA sequence in positioning nucleosomes.

PMID- 21723368
TI  - Automaton models of computational genetic regulatory networks with combinatorial
      gene-protein interactions.
AB  - In this paper, we present an approach for modeling computational genetic
      regulatory networks with multi-threshold protein concentration and combinatorial
      gene-protein interactions. We first present a gene automata model that describes
      the activities of a single gene, and discuss the construction of a network
      automaton model that describes the complete behavior of a gene network. To model
      the gene-protein interaction in the given gene network, we define the basic
      interaction, in the form of an automaton, that characterizes the interaction
      between a protein and a gene. We then define the new concept of an inducible
      event and propose the AND- and OR-composition operations (based on this concept
      of an inducible event) for combining the basic interactions into a combinatorial
      interaction, which is also represented by an automaton. By taking the synchronous
      product over the combinatorial interaction automata, we obtain a composite
      interaction automaton describing the overall gene-protein interaction patterns in
      a given gene network. Subsequent imposition of this composite logical
      relationship on the network automaton model yields a complete description of the
      dynamical behavior of the gene network. We illustrate the effectiveness of our
      proposed approach in the modeling of (i) morphogenesis in Arabidopsis and (ii)
      regulation in phage lambda.

PMID- 21723369
TI  - Effect of capacitation on the endocannabinoid system of mouse sperm.
AB  - The presence of the elements of the endocannabinoid system (ECS) in sperm
      isolated from several species (from invertebrates to mammals, humans included)
      has supported the "evolutionary theory" that proposes endocannabinoids as check
      points in reproductive events like capacitation. In this study, we characterized
      the ECS elements at the mRNA, protein and functional levels in mouse sperm before
      and after capacitation. We found that the latter process increases the endogenous
      levels of the two major endocannabinoids (anandamide and 2-arachidonoylglycerol),
      through a decreased degradation and increased biosynthesis, respectively.
      Additionally, we found that the binding activity of cannabinoid receptors was not
      affected by sperm capacitation, whereas that of vanilloid receptor was reduced.
      Overall, our data demonstrate that mouse sperm have a fully functional ECS, and
      that capacitation alters the endogenous tone of the major endocannabinoids
      through distinct mechanisms.

PMID- 21723370
TI  - Ginkgo biloba treatment increases copulation but not nNOS activity in the medial
      preoptic area in male rats.
AB  - Nitric oxide (NO) is an important messenger in the central nervous system to
      mediate male copulatory behavior. EGb 761, a standardized extract of Gingko
      biloba, has been reported to facilitate male copulation in rats. The present
      study is to determine the effects of neuronal nitric oxide synthase (nNOS) in the
      medial preoptic area (MPOA) on copulation in male rats following EGb 761
      treatment. Adult male rats were treated with 50mg/kg of EGb 761 or distilled
      water by oral gavage for 14 consecutive days. The animals were sacrificed
      approximately 14h after the last behavioral test and MPOA brain tissues were
      collected for nNOS immunohistochemistry. EGb 761 treatment for 14 days
      significantly increased the intromission frequency compared to the vehicle
      treated controls on day 14. An increase in ejaculation frequency was also seen in
      the EGb 761-treated group compared to the vehicle-treated controls on day 14 and
      to the same group on day 0. However, EGb 761 treatment did not influence the
      number of nNOS-immunoreactive cells in the MPOA. These results suggest that
      enhanced male copulatory performance in sexually experienced rats administered
      EGb 761 may not be related to central nNOS activity in the MPOA.

PMID- 21723371
TI  - Reaction time effects due to imperative stimulus modality are absent when a
      startle elicits a pre-programmed action.
AB  - When an acoustic stimulus that is sufficiently intense to elicit a startle
      response is delivered in conjunction with the "go" signal in a simple reaction
      time (RT) task, RT is greatly reduced. It has been suggested that this effect is
      due to the startle interacting with voluntary response channels to directly
      trigger the pre-programmed action. Alternatively, it may be that the startling
      stimulus simply increases activation along the sensory and motor pathways
      allowing for faster stimulus-response processing. In the present study a
      startling acoustic stimulus (SAS) was presented in addition to a visual or an
      auditory imperative stimulus (IS) in a simple RT task. Results showed that the
      pre-programmed response was initiated much faster when participants were
      startled. However, while differences in RT due to IS modality were observed in
      control trials, this difference was absent for startle trials. This result
      indicates that the SAS does not simply speed processing along the normal stimulus
      response channels, but acts to release the pre-planned movement via a separate,
      faster neural pathway.

PMID- 21723372
TI  - Neurite outgrowth of dorsal root ganglia neurons is enhanced on aligned
      nanofibrous biopolymer scaffold with carbon nanotube coating.
AB  - Nerve regeneration and functional recovery have been a major issue following
      injury of nerve tissues. Electrospun nanofibers are known to be suitable
      scaffolds for neural tissue engineering applications. In addition, modified
      substrates often provide better environments for neurite outgrowth. This study
      was conducted to determine if multi-walled carbon nanotubes (MWCNTs)-coated
      electrospun poly (l-lactic acid-co-caprolactone) (PLCL) nanofibers improved the
      neurite outgrowth of rat dorsal root ganglia (DRG) neurons and focal adhesion
      kinase (FAK) expression of PC-12 cells. To accomplish this, the DRG neurons in
      either uncoated PLCL scaffolds (PLCL group) or MWCNTs-coated PLCL scaffolds
      (PLCL/CNT group) were cultured for nine days. MWCNTs-coated PLCL scaffolds showed
      improved neurite outgrowth of DRG neurons. Moreover, FAK expression was up
      regulated in the PLCL/CNT group when compared to the PLCL group in a non-time
      dependent manner. These findings suggest that MWCNTs-coated nanofibrous scaffolds
      may be alternative materials for nerve regeneration and functional recovery in
      neural tissue engineering.

PMID- 21723373
TI  - BDNF and GAP43 contribute to dynamic transhemispheric functional reorganization
      in rat brain after contralateral C7 root transfer following brachial plexus
      avulsion injuries.
AB  - It is known that contralateral seventh cervical nerve (C7) root transfer after
      brachial plexus avulsion injuries (BPAI) causes interhemispheric cortical
      functional reorganization. However, the potential mechanisms and the role of
      neurotrophic factors and/or growth-associated protein expression in the process
      of cerebral reorganization are not well understood. The present study identified
      the expression of brain-derived neurotrophic factor (BDNF) and growth-associated
      protein 43 (GAP43) mRNA in primary motor cortex after contralateral C7 root
      transfer following BPAI. BDNF and GAP43 mRNA levels were significantly increased
      in brain samples at both 6 and 9 months after contralateral C7 root transfer
      following BPAI, in comparison with the samples from the rats with BPAI only.
      These findings indicate that BDNF and GAP43 may play an important role during the
      dynamic transhemispheric functional reorganization.

PMID- 21723374
TI  - Synthesis of and signalling by small, redox active molecules in the plant immune
      response.
AB  - BACKGROUND: Reactive oxygen and nitrogen intermediates (ROIs and RNIs),
      respectively, are central features of the plant immune response. Rare, highly
      reactive protein cysteine (Cys) residues of low pKa are a major target for these
      intermediates. In this context, S-nitrosylation, the addition of a nitric oxide
      (NO) moiety to a Cys thiol to form an S-nitrosothiol (SNO), is emerging as a key,
      redox-based post-translational modification during plant immune function.
      METHODS: Here, we describe some recent insights into how ROIs and RNIs are
      synthesized and how these small, redox active molecules help orchestrate the
      plant defence response. RESULTS: The reviewed data highlights the growing
      importance of ROIs and RNIs in orchestrating the development of plant immunity
      and provides insights into the molecular mechanisms underpinning their function.
      GENERAL SIGNIFICANCE: Signalling via small, redox active molecules is a key
      feature underpinning a diverse series of signal transduction networks in
      eukaryotic cells. Therefore, insights into the mechanisms that support the
      activity of these molecules may have potentially wide significance. This article
      is part of a Special Issue entitled: Regulation of cellular processes by S
      nitrosylation.

PMID- 21723375
TI  - Nitroalkylation--a redox sensitive signaling pathway.
AB  - Redox-sensitive posttranslational modification emerged as important signaling
      mechanisms. Besides other posttranslational modifications nitroalkylation by
      nitrated fatty acids mediate favorable anti-inflammatory effects. This review
      gives an overview of the generation and the reactivity of nitrated fatty acids.
      Additionally, it provides insights into the so far described pathways regulated
      by nitrated fatty acids. This article is part of a Special Issue entitled
      Regulation of Cellular Processes by S-nitrosylation.

PMID- 21723376
TI  - Age-related auditory deficits in temporal processing in F-344 rats.
AB  - Older human listeners demonstrate perceptual deficits in temporal processing even
      when audibility has been controlled. These age-related auditory deficits in
      temporal processing are thought to originate in the central auditory pathway.
      Precise temporal processing is necessary to detect and discriminate auditory cues
      such as modulation frequency, modulation depth and envelope shape which are
      critical for perception of speech and environmental sounds. This study aims to
      further understanding of temporal processing in aging using non-invasive
      electrophysiological measurements. Amplitude modulation following responses
      (AMFRs) and frequency modulation following responses (FMFRs) were recorded from
      aged (92-95-weeks old) and young (9-12-weeks old) Fischer-344 (F-344) rats for
      sinusoidally amplitude modulated (sAM) tones, sinusoidally frequency modulated
      (sFM) tones and ramped and damped amplitude modulation (AM) stimuli which differ
      in their envelope shapes. The modulation depth for the sAM and sFM stimuli and
      envelope shape for the ramped and damped stimuli were systematically varied.
      There was a monotonic decrease in AMFR and FMFR amplitudes with decreases in
      modulation depth across age for sAM and sFM stimuli. There was no significant
      difference between the response amplitudes of the young and aged animals for the
      largest modulation depths. However, a reduction in modulation depth resulted in a
      significant decrease in the response amplitudes and higher modulation detection
      thresholds for sAM and sFM stimuli with age. The aged animals showed
      significantly lower response amplitudes for ramped stimuli but not for damped
      stimuli. Cross correlating the responses with the ramped, symmetric, or damped
      stimulus envelopes revealed a decreased fidelity in encoding envelope shapes with
      age. These results indicate that age related temporal processing deficits become
      apparent only with reduced modulation depths or when discriminating envelope
      shapes. This has implications for psychophysical or diagnostic testing as well as
      for constraining potential cellular and network mechanisms responsible for these
      deficits.

PMID- 21723377
TI  - Prenatal stress induces long term stress vulnerability, compromising stress
      response systems in the brain and impairing extinction of conditioned fear after
      adult stress.
AB  - Stress is a risk factor for the development of affective disorders, including
      depression, post-traumatic stress disorder, and other anxiety disorders. However,
      not all individuals who experience either chronic stress or traumatic acute
      stress develop such disorders. Thus, other factors must confer a vulnerability to
      stress, and exposure to early-life stress may be one such factor. In this study
      we examined prenatal stress (PNS) as a potential vulnerability factor that may
      produce stable changes in central stress response systems and susceptibility to
      develop fear- and anxiety-like behaviors after adult stress exposure. Pregnant
      Sprague-Dawley rats were immobilized for 1 h daily during the last week of
      pregnancy. Controls were unstressed. The male offspring were then studied as
      adults. As adults, PNS or control rats were first tested for shock-probe
      defensive burying behavior, then half from each group were exposed to a combined
      chronic plus acute prolonged stress (CAPS) treatment, consisting of chronic
      intermittent cold stress (4  degrees C, 6 h/d, 14 days) followed on day 15 by a
      single session of sequential acute stressors (social defeat, immobilization, cold
      swim). After CAPS or control treatment, different groups were tested for open
      field exploration, social interaction, or cued fear conditioning and extinction.
      Rats were sacrificed at least 5 days after behavioral testing for measurement of
      tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) expression in specific
      brain regions, and plasma adrenocorticotropic hormone (ACTH) and corticosterone.
      Shock-probe burying, open field exploration and social interaction were
      unaffected by any treatment. However, PNS elevated basal corticosterone,
      decreased GR protein levels in hippocampus and prefrontal cortex, and decreased
      TH mRNA expression in noradrenergic neurons in the dorsal pons. Further, rats
      exposed to PNS plus CAPS showed attenuated extinction of cue-conditioned fear.
      These results suggest that PNS induces vulnerability to subsequent adult stress,
      resulting in an enhanced fear-like behavioral profile, and dysregulation of brain
      noradrenergic and hypothalamic-pituitary-adrenal axis (HPA) activity.

PMID- 21723378
TI  - WITHDRAWN: Comprehensive evaluation of neuroprotective effects of Ginkgo biloba
      extract EGB against ischemic stroke.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21723379
TI  - Inhibition of HIV-1 reverse transcriptase, toxicological and chemical profile of
      Calophyllum brasiliense extracts from Chiapas, Mexico.
AB  - Calophyllum species are sources of calanolides, which inhibit human
      immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). The hexane
      extract of the leaves from C. brasiliense collected in Soconusco, State of
      Chiapas, Mexico, analyzed by HPLC showed to contain apetalic acid, calanolides B,
      and C. It showed potent anti-HIV-1 RT inhibition (IC(50)=20.2 MUg/ml), but was
      not toxic in mice (LD(50)=1.99 g/kg). The histological study of the mice treated
      at the highest dose revealed no alteration on hepatocytes, and an increase in the
      number of spleen megakaryocytes. These results suggest this extract is suitable
      to continue studies for developing a phytodrug against HIV-1.

PMID- 21723380
TI  - Genetic variability and population structure in Sapindus emarginatus Vahl from
      India.
AB  - Sapindus emarginatus is an economically important tropical tree species sparsely
      distributed in different geographical provinces like Gangetic Plains, Western
      Ghats, and Deccan Plateau in India. In the present paper estimation of genetic
      variability within and among 41 accessions representing five populations was
      carried out using 3 single primer amplification reaction (SPAR) methods viz.
      RAPD, DAMD and ISSR. The cumulative data analysis was carried out for all three
      SPAR methods, and showed 82.32% polymorphism across all the accessions of S.
      emarginatus. Jaccard's similarity values among 41 accessions ranged from 0.15 to
      0.49 with an average value of 0.37. The intra-population genetic diversity
      revealed highest values of Nei's genetic diversity (0.19,) Shannon information
      index (0.29) and polymorphic loci (55.18%), among the accessions of Gujarat (GJ)
      population, while the corresponding lowest values were (0.10), (0.15) and
      (26.40%) respectively among the accessions of Rajasthan (RJ) population. The
      maximum inter-population average genetic distance (0.20) was between Karnataka
      (KA) and RJ, while the corresponding least genetic distance (0.06) was between
      Allahabad (AL) and Varanasi (VS) populations. The analysis of molecular variance
      (AMOVA) revealed maximum percentage of variation among individuals of populations
      (72%) followed by 16% among regions and 12% among populations. Principal
      coordinate analysis (PCA) of cumulative data also supported the clustering
      pattern in the UPGMA dendrogram. These results suggest that genetic diversity is
      corroborating with the geographical diversity. Mantel's test was performed which
      revealed a highly significant correlation between cumulative vs RAPD, and showed
      the maximum (0.93) correlation coefficient, followed by cumulative vs ISSR (0.78)
      and cumulative vs DAMD (0.91) respectively, and this clearly indicates that the
      SPAR methods (RAPD, DAMD and ISSR) are sufficiently informative and are suitable
      to analyze the genetic variability within and among the populations of S.
      emarginatus.

PMID- 21723381
TI  - An SRp75/hnRNPG complex interacting with hnRNPE2 regulates the 5' splice site of
      tau exon 10, whose misregulation causes frontotemporal dementia.
AB  - Tau is a neuronal-specific microtubule-associated protein that plays an important
      role in establishing neuronal polarity and maintaining the axonal cytoskeleton.
      Aggregated tau is the major component of neurofibrillary tangles (NFTs),
      structures present in the brains of people affected by neurodegenerative diseases
      called tauopathies. Tauopathies include Alzheimer's disease (AD), frontotemporal
      dementia with Parkinsonism (FTDP-17), the early onset dementia observed in Down
      syndrome (DS; trisomy 21) and the dementia component of myotonic dystrophy type 1
      (DM1). Splicing misregulation of adult-specific exon 10, which codes for a
      microtubule binding domain, results in expression of abnormal ratios of tau
      isoforms, leading to FTDP-17. Positions 3 to 19 of the intron downstream of exon
      10 define a hotspot of splicing regulation: the region diverges between humans
      and rodents, and point mutations within it result in tauopathies. In this study,
      we investigated three regulators of exon 10 splicing: serine/arginine-rich
      protein SRp75 and heterogeneous nuclear ribonucleoproteins hnRNPG and hnRNPE2.
      SRp75 and hnRNPG inhibit splicing of exon 10 whereas hnRNPE2 activates it. Using
      co-transfections, co-immunoprecipitations and RNAi we discovered that SRp75 binds
      to the proximal downstream intron of tau exon 10 at the FTDP-17 hotspot region;
      and that hnRNPG and hnRNPE2 interact with SRp75. Thus, increased exon 10
      inclusion in FTDP mutants may arise from weakened SRp75 binding. This work
      provides insights into the splicing regulation of the tau gene and into possible
      strategies for correcting the imbalance in tauopathies caused by changes in the
      ratio of exon 10.

PMID- 21723382
TI  - Molecular characterization of the iron binding protein ferritin in Eisenia andrei
      earthworms.
AB  - Ferritin is a storage protein that plays a key role in iron metabolism. In this
      study, we report on the sequence characterization of a ferritin-coding cDNA in
      Eisenia andrei earthworms isolated by RT-PCR using degenerated primers, and we
      suggest the presence of a putative IRE in the 5'-UTR of ferritin mRNA. The
      obtained ferritin sequence was compared with those of other animals showing
      sequence and structure homology in consensus sites, including the iron-responsive
      element (IRE) and ferroxidase centers. Despite the sequence homology in the E.
      andrei mRNA of ferritin with the sequences of other animals in consensus IRE
      sites, the presented cytosine in the IRE of E. andrei ferritin in the expected
      position does not form a conventional bulge. The presence of ferritin in the
      coelomic fluid of E. andrei was proven by iron staining assay. Moreover,
      aconitase activity in the coelomic fluid was assessed by aconitase assay,
      suggesting the presence of an iron regulatory protein. Quantitative analysis
      revealed changes in the gene expression levels of ferritin in coelomocytes in
      response to bacterial challenge, reaching the maximum level 8h after the
      stimulation with both Gram-positive and Gram-negative bacteria.

PMID- 21723383
TI  - Photoirradiation of dehydropyrrolizidine alkaloids--formation of reactive oxygen
      species and induction of lipid peroxidation.
AB  - Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are
      probably the most common poisonous plants affecting livestock, wildlife, and
      human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro
      PAs) that bind cellular protein and DNA, leading to hepatotoxicity and
      genotoxicity, including tumorigenicity. In this study we report that UVA
      photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline,
      dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline,
      dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70
      J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid
      peroxidation in a light dose-responsive manner. When irradiated in the presence
      of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation
      was enhanced when methanol was replaced by deuterated methanol. These results
      suggest that singlet oxygen is a photo-induced product. When irradiated in the
      presence of superoxide dismutase, the level of lipid peroxidation decreased,
      indicating that lipid peroxidation is also mediated by superoxide. Electron spin
      resonance (ESR) spin trapping studies confirmed that both singlet oxygen and
      superoxide anion radical were formed during photoirradiation. These results
      indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen
      species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation
      of the parent PAs and other PA metabolites, including PA N-oxides, under similar
      experimental conditions did not produce lipid peroxidation. It is known that PAs
      induce skin cancer and are secondary (hepatogenous) photosensitization agents.
      Our results suggest that dehydro-PAs are the active metabolites responsible for
      skin cancer formation and PA-induced secondary photosensitization.

PMID- 21723384
TI  - Gastroprotective activity of Zanthoxylum rhoifolium Lam. in animal models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The stem barks of Zanthoxylum rhoifolium Lam.
      (Rutaceae), locally known as "mamica de cadela", are popularly used in
      dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating
      flatulence and colic. The objective of this study was to evaluate the
      gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR)
      stem barks in acute gastric lesion models, investigating their possible
      mechanisms. MATERIALS AND METHODS: Mice were used for the evaluation of the acute
      toxicity, and mice and rats to study the gastroprotective activity. The
      gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol
      and indomethacin-induced gastric lesion models in mice, hypothermic-restraint
      stress, and ischemia/reperfusion in rats. In the investigation of the
      gastroprotective mechanisms of EEZR, the participation of the NO-synthase
      pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein
      sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced
      gastric mucosa lesion model and the quantification of the gastric mucus and the
      antisecretory activity through pylorus ligature model in rats were analyzed.
      RESULTS: The animals did not present any signs of acute toxicity for the EEZR (up
      to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR
      (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute
      ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion
      induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a
      gastroprotective activity in the indomethacin-induced ulcer model.
      Gastroprotection of EEZR was significantly decreased in pre-treated mice with l
      NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels
      inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of
      the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in
      ethanol-treated animals. Furthermore, the extract (500 mg/kg) significantly
      increased the mucus production, however, the gastric secretion parameters
      (volume, [H(+)], pH) did not show any alteration. CONCLUSIONS: Our results
      indicate that the ethanolic extract of Zanthoxylum rhoifolium exhibits a
      significant gastroprotection, because it inhibits the formation of gastric
      lesions using different models. The release of the nitric oxide, the opening of
      the K(ATP) channels, the participation of the non-protein sulfhydril groups (NP
      SH), catalase and the increase of mucous secretion seem to be involved in the
      gastroprotection activity of the EEZR. Nevertheless, this activity does not seem
      to be related to antisecretory mechanisms.

PMID- 21723385
TI  - Cell aging and social disadvantage: perspectives on mechanisms underlying health
      disparities from "across the pond".

PMID- 21723386
TI  - The distribution of an AVT V1a receptor in the brain of a sex changing fish,
      Epinephelus adscensionis.
AB  - The present study describes the distribution of an arginine vasotocin (AVT) V1a
      receptor (AVTr) throughout the brain of a sex-changing grouper, rock hind
      Epinephelus adscensionis. The objectives of this study were to describe the AVTr
      distribution in the brain of rock hind for potential linkages of the AVT hormone
      system with sex-specific behaviors observed in this species and to examine sex
      specific differences that might exist. An antibody was designed for rock hind
      AVTr against the deduced amino acid sequence for the third intracellular loop.
      Protein expression, identified with immunohistochemistry showed high concordance
      with mRNA expression, identified with in situ hybridization. AVTr protein and
      mRNA expression was widely distributed throughout the brain, indicating that AVT
      may act as a neuromodulator via this V1a receptor subtype. AVTr protein and mRNA
      were present in regions associated with behavior, reproduction and spatial
      learning, as well as sensory functions such as vision, olfaction and lateral line
      sensory processing. We observed high AVTr expression in granular cell formations
      in the internal cellular layer of olfactory bulbs, torus longitudinalis, granular
      layer of the corpus cerebellum, valvula of the cerebellum, nuclei of the lateral
      and posterior recesses, and granular eminence. High protein and mRNA expression
      was also observed in the preoptic area, anterior hypothalamus, and habenular
      nucleus. No obvious sex differences were noted in any region of the rock hind
      brain.

PMID- 21723387
TI  - Complex I syndrome in myocardial stunning and the effect of adenosine.
AB  - Isolated rabbit hearts were exposed to ischemia (I; 15 min) and reperfusion (R; 5
      30 min) in a model of stunned myocardium. I/R decreased left-ventricle O(2)
      consumption (46%) and malate-glutamate-supported mitochondrial state 3
      respiration (32%). Activity of complex I was 28% lower after I/R. The pattern
      observed for the decline in complex I activity was also observed for the
      reduction in mitochondrial nitric oxide synthase (mtNOS) biochemical (28%) and
      functional (50%) activities, in accordance with the reported physical and
      functional interactions between complex I and mtNOS. Malate-glutamate-supported
      state 4 H(2)O(2) production was increased by 78% after I/R. Rabbit heart Mn-SOD
      concentration in the mitochondrial matrix (7.4+/-0.7 MUM) was not modified by
      I/R. Mitochondrial phospholipid oxidation products were increased by 42%, whereas
      protein oxidation was only slightly increased. I/R produced a marked (70%)
      enhancement in tyrosine nitration of the mitochondrial proteins. Adenosine
      attenuated postischemic ventricular dysfunction and protected the heart from the
      declines in O(2) consumption and in complex I and mtNOS activities and from the
      enhancement of mitochondrial phospholipid oxidation. Rabbit myocardial stunning
      is associated with a condition of dysfunctional mitochondria named "complex I
      syndrome." The beneficial effect of adenosine could be attributed to a better
      regulation of intracellular cardiomyocyte Ca(2+) concentration.

PMID- 21723388
TI  - Generation and suppression of singlet oxygen in hair by photosensitization of
      melanin.
AB  - We have studied the spectroscopic properties of hair (white, blond, red, brown,
      and black) under illumination with visible light, giving special emphasis to the
      photoinduced generation of singlet oxygen ((1)O(2)). Irradiation of hair shafts
      (lambda(ex)>400 nm) changed their properties by degrading the melanin. Formation
      of C3 hydroperoxides in the melanin indol groups was proven by (1)H NMR. After
      532-nm excitation, all hair shafts presented the characteristic (1)O(2) emission
      (lambda(em)=1270 nm), whose intensity varied inversely with the melanin content.
      (1)O(2) lifetime was also shown to vary with hair type, being five times shorter
      in black hair than in blond hair, indicating the role of melanin as a (1)O(2)
      suppressor. Lifetime ranged from tenths of a nanosecond to a few microseconds,
      which is much shorter than the lifetime expected for (1)O(2) in the solvents in
      which the hair shafts were suspended, indicating that (1)O(2) is generated and
      suppressed inside the hair structure. Both eumelanin and pheomelanin were shown
      to produce and to suppress (1)O(2), with similar efficiencies. The higher amount
      of (1)O(2) generated in blond hair and its longer lifetime is compatible with the
      stronger damage that light exposure causes in blond hair. We propose a model to
      explain the formation and suppression of (1)O(2) in hair by photosensitization of
      melanin with visible light and the deleterious effects that an excess of visible
      light may cause in hair and skin.

PMID- 21723389
TI  - Hyaluronan reduces inflammation in experimental arthritis by modulating TLR-2 and
      TLR-4 cartilage expression.
AB  - Previous studies have reported that low molecular mass HA and highly polymerized
      HA respectively elicited pro- and anti-inflammatory responses by modulating the
      toll-like receptor 4 (TLR-4) and the TLR-2. The activation of TLR-4 and TLR-2
      mediated by collagen-induced arthritis (CIA) induces the myeloid differentiation
      primary response protein (MyD88) and the tumor necrosis factor receptor
      associated factor 6 (TRAF6), and ends with the liberation of NF-kB which, in
      turn, stimulates pro-inflammatory cytokine production. The aim of this study was
      to investigate the influence of high molecular weight HA at different
      concentrations on TLR-4 and TLR-2 modulation in CIA in mice. Arthritis was
      induced in mice via intradermal injection of an emulsion containing bovine type
      II collagen in complete Freund's adjuvant. Mice were treated with HA
      intraperitoneally daily for 30days. CIA increased TLR-4, TLR-2, MyD88 and TRAF6
      mRNA expression and the related protein in the cartilage of arthritic joints.
      High levels of both mRNA and related protein were also detected for tumor
      necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL-1-beta), interleukin-17
      (IL-17), matrix metalloprotease-13 (MMP-13) and inducible nitric oxide synthase
      (iNOS) in the joint of arthritic mice. HA treatment significantly limited CIA
      incidence and decreased all the parameters up-regulated by CIA. The improvement
      of biochemical parameters was also supported by histological analysis, plasma and
      synovial fluid HA levels. These results suggest that the TLR-4 and TLR-2 play an
      important role in the arthritis mechanism and the interaction/block of HA at high
      molecular mass may reduce inflammation and cartilage injury.

PMID- 21723390
TI  - End functionalized polymeric system derived from pyrrolidine provide high
      transfection efficiency.
AB  - Chemical architecture and functionality play an important role in the physico
      chemical properties of cationic polymers with applications as gene vectors. In
      this study, linear homopolymers of N-ethyl pyrrolidine methacrylamide (EPA),
      copolymers of EPA with N,N-dimethylacrylamide (DMA) and oligomers of EPA were
      synthesized, and the resulting structures were evaluated for their transfection
      efficiency as non-viral gene vectors. Specifically, polymer species with high and
      low molecular weights (120-2.6 kDa) and different functionalities (tertiary
      amines as side chains and primary amine as chain end) were prepared as non
      crosslinked, linear homopolymers, copolymers and oligomers, respectively.
      Polymer/DNA complexes (polyplexes) formation was evaluated by agarose gel
      electrophoresis, showing that all systems complexed with DNA in all P/N ratios
      with the exception of the EPA homopolymer. Furthermore, light scattering
      measurements and transmission electronic microscopy (TEM) showed different size
      (50-450 nm) and morphology depending on the composition and concentration of the
      polyplex systems. Cell viability and proliferation after contact with polymer and
      polyplexes were studied using 3T3 fibroblasts, and the systems showed an
      excellent biocompatibility at 2 and 4 days. Transfection studies were performed
      with plasmid Gaussian luciferase kit and were found that the highest transfection
      efficiency in serum free was obtained with oligomers from the P/N ratio of 1/6 to
      1/10. Transfection values of the functionalized oligomers with respect to the
      control linear poly (dimethylaminoethyl methacrylate) [poly (DMAEMA)] are very
      interesting in the presence of serum. Haemolysis for these polymers values below
      1%, which provide attractive potential applications in gene therapy with these
      non-toxic readsorbable polymers.

PMID- 21723391
TI  - Cell-matrix adhesions in 3D.
AB  - Cells in a three-dimensional (3D) extracellular matrix environment often display
      different properties and behavior compared to cells cultured on a two-dimensional
      (2D) substrate. Recent studies characterizing the cell-matrix adhesions formed by
      cells within a 3D matrix have arrived at contradictory conclusions regarding the
      presence and composition of adhesions. Here we review this literature, and
      provide a comparative compilation of information found in published studies from
      the 3D cell-matrix adhesion field in order to identify shared and divergent
      conclusions and conceptually important areas that require further research.
      Although there is a general consensus that discrete cell-matrix adhesions exist
      in various 3D matrix environments, there are specific exceptions, particularly in
      cells undergoing amoeboid migration. There are also technical issues to consider
      when imaging adhesions in 3D matrix; for example, over-expression of a
      cytoskeletal cell adhesion component can potentially cloud the visualization of
      adhesions and even alter the mode of cell migration. Properties such as stiffness
      and local matrix topography may also affect the composition of cell-matrix
      adhesions. For example, even though cells contain integrin-based 3D adhesions,
      there can be substantial variability within these adhesions in the presence of
      force-dependent cytoskeletal components such as vinculin. These new findings and
      ideas provide promising new leads for understanding the regulation and function
      of cell-matrix adhesions in 3D matrix.

PMID- 21723392
TI  - A galactosamine-mediated drug delivery carrier for targeted liver cancer therapy.
AB  - In order to minimize the side effect of cancer chemotherapy, a novel
      galactosamine-mediated drug delivery carrier, galactosamine-conjugated albumin
      nanoparticles (GAL-AN), was developed for targeted liver cancer therapy. The
      albumin nanoparticles (AN) and doxorubicin-loaded AN (DOX-AN) were prepared by
      the desolvation of albumin in the presence of glutaraldehyde crosslinker.
      Morphological study indicated the spherical structure of these synthesized
      particles with an average diameter of around 200 nm. The functional ligand of
      galactosamine (GAL) was introduced onto the surfaces of AN and DOX-AN via
      carbodiimide chemistry to obtain GAL-AN and GAL-DOX-AN. Cellular uptake and
      kinetic studies showed that GAL-AN is able to be selectively incorporated into
      the HepG2 cells rather than AoSMC cells due to the existence of
      asialoglycoprotein receptors on HepG2 cell surface. The cytotoxicity, measured by
      MTT test, indicated that AN and GAL-AN are non-toxic and GAL-DOX-AN is more
      effective in HepG2 cell killing than that of DOX-AN. As such, our results implied
      that GAL-AN and GAL-DOX-AN have specific interaction with HepG2 cells via the
      recognition of GAL and asialoglycoprotein receptor, which renders GAL-AN a
      promising anticancer drug delivery carrier for liver cancer therapy.

PMID- 21723393
TI  - Library-based methods for identification of soluble expression constructs.
AB  - When expression or crystallisation of a protein target in its wild-type full
      length form proves problematic, a common strategy is to divide it into
      subconstructs comprising one or more domains. Rational construct design is not
      always successful, especially with targets for which there are few similar
      sequences to generate multiple sequence alignments. Even when this is possible,
      expression constructs may still fail to yield soluble protein, commonly
      expressing insolubly or at unusable yields. To address this, several new methods
      have been described that borrow concepts from the field of directed evolution
      whereby a random library is generated encompassing construct diversity; this is
      then screened to identify soluble constructs empirically. Here, we review
      progress in this area.

PMID- 21723394
TI  - An inflammatory CC chemokine of Cynoglossus semilaevis is involved in immune
      defense against bacterial infection.
AB  - Chemokines are a family of small cytokines that regulate leukocyte migration.
      Based on the arrangement of the first two cysteine residues, chemokines are
      classified into four groups called CXC(alpha), CC(beta), C, and CX(3)C. In this
      study, we identified a CC chemokine, CsCCK1, from half-smooth tongue sole
      (Cynoglossus semilaevis) and analyzed its biological activity. The deduced amino
      acid sequence of CsCCK1 contains 111 amino acid residues and is phylogenetically
      belonging to the CCL19/21/25 group of CC chemokines. CsCCK1 possesses a DCCL
      motif that is highly conserved among CC chemokines. Quantitative real time RT-PCR
      analysis showed that the expression of CsCCK1 was relatively abundant in immune
      organs under normal physiological conditions and was upregulated by experimental
      infection of a bacterial pathogen. Purified recombinant CsCCK1 (rCsCCK1) induced
      chemotaxis in peripheral blood leukocytes (PBL) of both tongue sole and turbot
      (Scophthalmus maximus) in a dose-dependent manner. Mutation of the CC residues in
      the DCCL motif by serine substitution completely abolished the biological
      activity of rCsCCK1. When rCsCCK1, but not the mutant protein, was added to the
      cell culture of PBL, it enhanced cellular resistance against intracellular
      bacterial infection. Taken together, these results indicate that CsCCK1 is a
      functional CC chemokine whose biological activity depends on the DCCL motif and
      that CsCCK1 plays a role in host immune defense against bacterial infection.

PMID- 21723395
TI  - Imaging genetics in multiple sclerosis: a volumetric and diffusion tensor MRI
      study of APOE epsilon4.
AB  - Evidence linking the epsilon4 allele of APOE to more severe brain MRI
      abnormalities in multiple sclerosis (MS) has been conflicting and limited to
      studies of lesion load and whole brain atrophy. The purpose of the present study
      was to determine whether the epsilon4 allele of APOE is associated with more
      extensive brain pathology in MS using structural and diffusion tensor MRI. Using
      a case-control design, 43 MS patients with the epsilon4 allele and 47 epsilon4
      negative MS patients underwent structural and diffusion tensor imaging (DTI) at
      3T. Hypo- and hyperintense lesion volumes, whole brain and medial temporal
      volumes, and DTI parameters (fractional anisotropy (FA) and mean diffusivity
      (MD)) in normal-appearing brain tissue and lesions were compared between the
      groups. epsilon4+ and epsilon4- MS patients were well-matched on demographic
      characteristics, disease variables, and proportions receiving disease-modifying
      therapy. epsilon4+ and epsilon4- patients did not differ on any MRI or DTI
      measure. This study refutes a role for the epsilon4 allele in MRI abnormalities
      in MS, particularly those linking epsilon4 to greater T1 hypointense lesion
      volume and brain atrophy. Previous work on this putative gene-MRI relationship is
      extended by comparing DTI measures within lesions and normal-appearing brain
      tissue. A lack of differences in medial temporal regions, areas that have been
      linked to epsilon4-associated changes in health and disease, further supports the
      conclusion that that epsilon4 is not associated with more subtle MRI markers of
      brain pathology in MS.

PMID- 21723396
TI  - Novelty increases the mesolimbic functional connectivity of the substantia
      nigra/ventral tegmental area (SN/VTA) during reward anticipation: Evidence from
      high-resolution fMRI.
AB  - Reward and novelty are potent learning signals that critically rely on
      dopaminergic midbrain responses. Recent findings suggest that although reward and
      novelty are likely to interact, both functions may be subserved by distinct
      neuronal clusters. We used high-resolution functional magnetic resonance imaging
      (fMRI) to isolate neural responses to reward and novelty within the human
      substantia nigra/ventral tegmental area (SN/VTA) complex to investigate the
      spatial delineation and integration of reward- and novelty-related activity
      clusters. We demonstrate that distinct clusters within the caudal portion of the
      medial SN/VTA and the lateral portion of the right SN are predominantly modulated
      by the anticipation of reward, while a more rostral part of the medial SN/VTA was
      exclusively modulated by novelty. In addition, the caudal medial SN/VTA cluster
      embodied an interaction between novelty and reward where novelty selectively
      increased reward-anticipation responses. This interaction, in turn, was
      paralleled by differences in the functional-connectivity patterns of these SN/VTA
      regions. Specifically, novel as compared to familiar reward-predictive stimuli
      increased the functional connectivity of the medial SN/VTA with mesolimbic
      regions, including the nucleus accumbens and the hippocampus, as well as with the
      primary visual cortex. This functional correlation may highlight how afferents of
      the medial SN/VTA provide integrative information about novelty and reward, or,
      alternatively, how medial SN/VTA activity may modulate memory processes for novel
      events associated with rewards.

PMID- 21723397
TI  - A robust cerebral asymmetry in the infant brain: the rightward superior temporal
      sulcus.
AB  - In order to understand how genetic mutations might have favored language
      development in our species, we need a better description of the human brain at
      the beginning of life. As the linguistic network mainly involves the left
      perisylvian regions in adults, we used anatomical MRI to study the structural
      asymmetries of these regions in 14 preverbal infants. Our results show four
      significant asymmetries. First and foremost, they stress an important but little
      known asymmetry: the larger depth of the right superior temporal sulcus (STS) at
      the base of Heschl's gyrus. Then, we characterized the early forward and upward
      shift of the posterior end of the right Sylvian fissure, the elongation of the
      left planum temporale as well as the thickening of the left Heschl's gyrus. The
      rightward bias of the STS is robust and large, and is not correlated with the
      leftward asymmetries of the planum and Heschl's gyrus, suggesting that different
      morphogenetic factors drive these asymmetries. As this sulcus is engaged in
      multiple high-level functions (e.g. language and theory of mind), and has been
      spotted as abnormal in several developmental disorders (e.g. schizophrenia,
      autism), this early rightward asymmetry should be further explored as a target
      for a genetic evolutionary pressure.

PMID- 21723398
TI  - Bayesian relaxed clock estimation of divergence times in foraminifera.
AB  - Accurate and precise estimation of divergence times during the Neo-Proterozoic is
      necessary to understand the speciation dynamic of early Eukaryotes. However such
      deep divergences are difficult to date, as the molecular clock is seriously
      violated. Recent improvements in Bayesian molecular dating techniques allow the
      relaxation of the molecular clock hypothesis as well as incorporation of multiple
      and flexible fossil calibrations. Divergence times can then be estimated even
      when the evolutionary rate varies among lineages and even when the fossil
      calibrations involve substantial uncertainties. In this paper, we used a Bayesian
      method to estimate divergence times in Foraminifera, a group of unicellular
      eukaryotes, known for their excellent fossil record but also for the high
      evolutionary rates of their genomes. Based on multigene data we reconstructed the
      phylogeny of Foraminifera and dated their origin and the major radiation events.
      Our estimates suggest that Foraminifera emerged during the Cryogenian (650-920
      Ma, Neo-Proterozoic), with a mean time around 770 Ma, about 220 Myr before the
      first appearance of reliable foraminiferal fossils in sediments (545 Ma). Most
      dates are in agreement with the fossil record, but in general our results suggest
      earlier origins of foraminiferal orders. We found that the posterior time
      estimates were robust to specifications of the prior. Our results highlight inter
      species variations of evolutionary rates in Foraminifera. Their effect was
      partially overcome by using the partitioned Bayesian analysis to accommodate rate
      heterogeneity among data partitions and using the relaxed molecular clock to
      account for changing evolutionary rates. However, more coding genes appear
      necessary to obtain more precise estimates of divergence times and to resolve the
      conflicts between fossil and molecular date estimates.

PMID- 21723399
TI  - A large-scale phylogeny of Amphibia including over 2800 species, and a revised
      classification of extant frogs, salamanders, and caecilians.
AB  - The extant amphibians are one of the most diverse radiations of terrestrial
      vertebrates (>6800 species). Despite much recent focus on their conservation,
      diversification, and systematics, no previous phylogeny for the group has
      contained more than 522 species. However, numerous studies with limited taxon
      sampling have generated large amounts of partially overlapping sequence data for
      many species. Here, we combine these data and produce a novel estimate of extant
      amphibian phylogeny, containing 2871 species (~40% of the known extant species)
      from 432 genera (~85% of the ~500 currently recognized extant genera). Each
      sampled species contains up to 12,712 bp from 12 genes (three mitochondrial, nine
      nuclear), with an average of 2563 bp per species. This data set provides strong
      support for many groups recognized in previous studies, but it also suggests non
      monophyly for several currently recognized families, particularly in hyloid frogs
      (e.g., Ceratophryidae, Cycloramphidae, Leptodactylidae, Strabomantidae). To
      correct these and other problems, we provide a revised classification of extant
      amphibians for taxa traditionally delimited at the family and subfamily levels.
      This new taxonomy includes several families not recognized in current
      classifications (e.g., Alsodidae, Batrachylidae, Rhinodermatidae,
      Odontophrynidae, Telmatobiidae), but which are strongly supported and important
      for avoiding non-monophyly of current families. Finally, this study provides
      further evidence that the supermatrix approach provides an effective strategy for
      inferring large-scale phylogenies using the combined results of previous studies,
      despite many taxa having extensive missing data.

PMID- 21723400
TI  - Psychological health impact on 2-year changes in pain and function in persons
      with knee pain: data from the Osteoarthritis Initiative.
AB  - OBJECTIVE: We determined whether baseline depressive symptoms, knee-related
      confidence and general psychological distress influenced changes in pain and
      function during 2 years of follow-up. DESIGN: We included persons in the
      Osteoarthritis Initiative (OAI) dataset with baseline pain of 1 or greater on a 0
      10 scale in at least one knee and no knee or hip surgery during the 2-year follow
      up (n=3407). The four outcome variables were repeated chair standing, 20 m walk
      and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain
      and Disability. Linear mixed effects models assessed the association of each
      mental health variable with the yearly change in each baseline adjusted outcome
      measure after controlling for covariates. RESULTS: Depressive symptoms were
      significantly predictive of worsening in most outcomes. The magnitude of
      worsening predicted for each year was small. For example, the dichotomized WOMAC
      Pain model indicated that depressed persons experience more rapid worsening than
      non-depressed persons at an average rate of 0.59 WOMAC points per year (95% CI
      0.176, 1.013, P=0.005). Similar significant but very small effects of depressive
      symptoms on other outcomes were observed. Knee confidence was not predictive of
      change. General psychological distress was predictive of change in 20-m walk and
      WOMAC Pain. CONCLUSIONS: The most consistent psychological predictor of yearly
      worsening was baseline depressive symptoms. Although a statistically robust
      predictor of outcome, given that change was very small and highly dependent on
      baseline status, our results indicate that a considerable degree of persistent
      depressive symptoms would be required to have a meaningful effect on future self
      reported outcome.

PMID- 21723401
TI  - Walking and chair rising performed in the daily life situation before and after
      total hip arthroplasty.
AB  - OBJECTIVE: An earlier study showed that 6 months after total hip arthroplasty
      (THA) patients' overall daily activity level had not increased, despite
      significant improvement in their perceived physical functioning. This discrepancy
      might be because postoperative recovery is not expressed by a more overall active
      lifestyle, but by the fact that patients could perform the individual activities
      of daily living (ADL) faster and/or for a longer period of time. The aim of this
      study was to assess whether patients perform ADL faster and/or for a longer
      period of time 6 months post-THA compared to baseline. Also examined was whether
      patients perform activities on the level of healthy matched controls. METHOD:
      Thirty patients were measured at home with an accelerometry-based Activity
      Monitor, pre-operatively and 6 months post-THA. Patients were matched with
      healthy controls on gender and age (+/-2 years). RESULTS: Compared with baseline,
      6 months post-THA the stride frequency and body motility during walking of
      patients had increased [56.1 (54.3, 57.8)strides/min vs 52.1 (50.3,
      54.1)strides/min; P-value<0.0001, and 0.265 (0.245, 0.286)g vs 0.219 (0.197,
      0.240)g; P-value<0.0001], and they rose faster from a chair [2.6 (2.5, 2.8)s vs
      3.0 (2.8, 3.2)s; P-value<0.0001]. Compared with controls, preoperative all
      patients had lower values for these parameters. Six months post-THA the stride
      frequency and body motility during walking were similar to that of controls, but
      patients rose slower from a chair than controls. CONCLUSION: Six months post-THA
      patients walked faster and rose from a chair faster compared to baseline.
      Patients walked as fast as healthy controls but took longer rising from a chair.

PMID- 21723402
TI  - Summary of the OA biomarkers workshop 2010 - genetics and genomics: new targets
      in OA.
AB  - On November fourth and fifth 2010 a group of more than 100 international
      investigators gathered in Atlanta for the second Osteoarthritis (OA) Biomarkers
      Global Initiative workshop titled "Genetics and Genomics: New Targets in OA". The
      first workshop took place in April 2009 and focused on in vitro (soluble)
      biomarkers whilst the third and final workshop will take place in 2012 and will
      focus on imaging biomarkers. The OA Research Society International (OARSI) has
      organized the workshops. In addition to OARSI, the National Institute of
      Arthritis, Musculoskeletal and Skin Diseases, the Arthritis Foundation, Amgen,
      Genzyme, the American Orthopaedic Society for Sports Medicine and Pfizer
      sponsored the second meeting. It was clear from this meeting that experiments in
      the genetics, epigenetics and genomics of OA, are yielding valuable insights into
      the etiology of this heterogeneous disease but that much still needs to be
      learnt. Combining genetic insights with conventional biomarkers and imaging
      modalities may provide scientists with the enhanced tools to understand this
      complex disease. With those tools in hand, clinicians and industry can develop
      protocols to ultimately improve patient care.

PMID- 21723403
TI  - Modulation of virulence and antibiotic susceptibility of enteropathogenic
      Escherichia coli strains by Enterococcus faecium probiotic strain culture
      fractions.
AB  - The increasing rate of antimicrobial resistance drastically reduced the
      efficiency of conventional antibiotics and led to the reconsideration of the
      interspecies interactions in influencing bacterial virulence and response to
      therapy. The aim of the study was the investigation of the influence of the
      soluble and cellular fractions of Enterococcus (E.) faecium CMGB16 probiotic
      culture on the virulence and antibiotic resistance markers expression in clinical
      enteropathogenic Escherichia (E.) coli strains. The 7 clinical enteropathogenic
      E. coli strains, one standard E. coli ATCC 25,922 and one Bacillus (B.) cereus
      strains were cultivated in nutrient broth, aerobically at 37  degrees C, for 24
      h. The E. faecium CMGB16 probiotic strain was cultivated in anaerobic conditions,
      at 37  degrees C in MRS (Man Rogosa Sharpe) broth, and co-cultivated with two
      pathogenic strains (B. cereus and E. coli O28) culture fractions (supernatant,
      washed sediment and heat-inactivated culture) for 6 h, at 37  degrees C. After co
      cultivation, the soluble and cellular fractions of the probiotic strain
      cultivated in the presence of two pathogenic strains were separated by
      centrifugation (6000 rpm, 10 min), heat-inactivated (15 min, 100  degrees C) and
      co-cultivated with the clinical enteropathogenic E. coli strains in McConkey
      broth, for 24 h, at 37  degrees C, in order to investigate the influence of the
      probiotic fractions on the adherence capacity and antibiotic susceptibility. All
      tested probiotic combinations influenced the adherence pattern of E. coli tested
      strains. The enteropathogenic E. coli strains susceptibility to aminoglycosides,
      beta-lactams and quinolones was increased by all probiotic combinations and
      decreased for amoxicillin-clavulanic acid. This study demonstrates that the
      plurifactorial anti-infective action of probiotics is also due to the modulation
      of virulence factors and antibiotic susceptibility expression in E. coli
      pathogenic strains.

PMID- 21723404
TI  - Detection of Porphyromonas gulae from subgingival biofilms of dogs with and
      without periodontitis.
AB  - A rapid PCR approach was developed to detect Porphyromonas gulae strains from
      subgingival samples of dogs with and with periodontitis. The presence of P. gulae
      was observed in 92% and 56%, respectively, in dogs with and without
      periodontitis. The new primer pair was specific to detect this microorganism, and
      this technique could be used to evaluate a correlation between periodontitis and
      P. gulae in companion animals.

PMID- 21723405
TI  - Lectins of living organisms. The overview.
AB  - Occurrence, organization, and functioning of lectins as well as their current
      classifications are under investigation. Results indicate importance of symbiotic
      lectins for clinical microecology. Lectins and lectin-based approaches have wide
      perspectives for medical biotechnology. Lectin terms, relationships between
      lectins and enzymes are discussed.

PMID- 21723406
TI  - Planning and response to radiation exposures.

PMID- 21723407
TI  - Behavioral and physiological responses of wild-caught European starlings (Sturnus
      vulgaris) to a minor, rapid change in ambient temperature.
AB  - Free-ranging animals continuously adjust to changes in their environment. The
      stress response, typified by increases in heart rate and glucocorticoids, is an
      important physiological response regulating these changes. This study
      investigated heart rate, corticosterone and behavioral responses of European
      starlings (Sturnus vulgaris) to a rapid 30min decrease in temperature using an
      air-conditioning unit. Ten wild-caught birds were divided into pairs and exposed
      to four different trials. Three trials were controls: undisturbed birds; exposing
      birds to only the noise of the air-conditioning unit; and exposing the birds to
      20 degrees C airflow. For the experimental trial birds were exposed to 12 degrees
      C air, leading to a rapid but modest 3 degrees C drop in ambient temperature
      inside the birdcages. Heart rate and behavior were recorded before and during
      trials, while blood samples were collected before and after each trial for
      corticosterone measurements. Cooling, but none of the control conditions, induced
      an increase in heart rate and corticosterone. Additionally, cooling led to an
      increase in perch hopping and feather ruffling. We conclude that minor changes in
      temperature can elicit a stress response in European starlings, which suggests
      that this may be an important mechanism by which animals cope with minor rapid
      environmental changes.

PMID- 21723408
TI  - Effects of high environmental ammonia on branchial ammonia excretion rates and
      tissue Rh-protein mRNA expression levels in seawater acclimated Dungeness crab
      Metacarcinus magister.
AB  - In the present study of the marine Dungeness crabs Metacarcinus magister, the
      long term effects of high environmental ammonia (HEA) on hemolymph ammonia and
      urea concentrations, branchial ammonia excretion rates and mRNA expression levels
      of the crustacean Rh-like ammonia transporter (RhMM), H(+)-ATPase (subunit B),
      Na(+)/K(+)-ATPase (alpha-subunit) and Na(+)/H(+)-exchanger (NHE) were
      investigated. Under control conditions, the crabs' hemolymph exhibited a total
      ammonia concentration of 179.3+/-14.5MUmol L(-1), while urea accounted for
      467.2+/-33.5MUmol L(-1), respectively. Both anterior and posterior gills were
      capable of excreting ammonia against a 16-fold inwardly directed gradient. Under
      control conditions, mRNA expression levels of RhMM were high in the gills in
      contrast to very low expression levels in all other tissues investigated,
      including the antennal gland, hepatopancreas, and skeletal muscle. After exposure
      to 1mmol L(-1) NH(4)Cl, hemolymph ammonia increased within the first 12h to ca.
      500umol L(-1) and crabs were able the keep this hemolymph ammonia level for at
      least 4 days. During this initial period, branchial RhMM and H(+)-ATPase (subunit
      B) mRNA expression levels roughly doubled. After 14 days of HEA exposure,
      hemolymph ammonia raised up to environmental levels, whereas urea levels
      increased by ca. 30%. At the same time, whole animal ammonia and urea excretion
      vanished. Additionally, branchial RhMM, H(+)-ATPase, Na(+)/K(+)-ATPase and NHE
      mRNA levels decreased significantly after long term HEA exposure, whereas
      expression levels of RhMM in the internal tissues increased substantially.
      Interestingly, crabs acclimated to HEA showed no mortality even after 4 weeks of
      HEA exposure. This suggests that M. magister possesses a highly adaptive
      mechanism to cope with elevated ammonia concentrations in its body fluids,
      including an up-regulation of an Rh-like ammonia transporter in the internal
      tissues and excretion or storage of waste nitrogen in a so far unknown form.

PMID- 21723409
TI  - Preliminary investigation of a mice model of Klebsiella pneumoniae subsp. ozaenae
      induced pneumonia.
AB  - In the present study, we comparatively assessed the pathophysiological mechanisms
      developed during lung infection of BALB/C female mice infected by an original
      wild type Klebsiella pneumoniae subsp. ozaenae strain (CH137) or by a referent
      subspecies K. pneumoniae. subsp. pneumoniae strain (ATCC10031). The mice infected
      with 2.106 CFU K. p. subsp. pneumoniae (n = 10) showed transient signs of
      infection and all of them recovered. All of those infected with 1.106 CFU K. p.
      subsp. ozaenae (n = 10) developed pneumonia within 24 h and died between 48 and
      72 h. Few macrophages, numerous polymorphonuclear cells and lymphocytes were
      observed in their lungs in opposite to K. p. subsp. pneumoniae. In
      bronchoalveolar lavage, a significant increase in MIP-2, IL-6, KC and MCP-1
      levels was only observed in K. p. subsp. ozaenae infected mice whereas high
      levels of TNF-alpha were evidenced with the two subspecies. Our findings
      indicated a lethal effect of a wild type K. p. subsp. ozaenae strain by acute
      pneumonia reflecting an insufficient alveolar macrophage response. This model
      might be of a major interest to comparatively explore the pathogenicity of K. p.
      subsp ozaenae strains and to further explore the physiopathological mechanisms of
      gram-negative bacteria induced human pneumonia.

PMID- 21723410
TI  - NOX1 participates in ROS-dependent cell death of colon epithelial Caco2 cells
      induced by Entamoeba histolytica.
AB  - Entamoeba histolytica, which causes amebic colitis and occasional liver abscesses
      in humans, can induce host cell death through apoptosis and necrosis. Recently,
      we have demonstrated that E. histolytica can induce cell death in neutrophils via
      diphenyleneiodonium-sensitive NADPH oxidase (NOX)-derived reactive oxygen species
      (ROS). Although there are enzyme systems similar to the phagocyte NADPH oxidase
      system in many non-phagocytic cell types, the signaling role of NOX-derived ROS
      in cell death of human colon epithelial cells induced by E. histolytica remains
      obscure. Incubation of colon epithelial Caco2 tumor cell lines with amebic
      trophozoites resulted in intracellular ROS generation and cell death in a caspase
      independent manner. Pretreatment with DPI, an inhibitor of NOX, strongly
      decreased E. histolytica-induced cell death in Caco2 cells. As identified by RT
      PCR, NOX1 transcripts were highly expressed in Caco2 cells. siRNA-mediated
      suppression of NOX1 protein significantly inhibited E. histolytica-induced cell
      death and ROS response in Caco2 cells. These results suggest that NOX1
      participates in the ROS-dependent cell death of colon epithelial cells induced by
      amebic adhesion during the early phase of intestinal amebiasis.

PMID- 21723411
TI  - The effects of macrophage source on the mechanism of phagocytosis and
      intracellular survival of Leishmania.
AB  - Leishmania spp. protozoa are obligate intracellular parasites that replicate in
      macrophages during mammalian infection. Efficient phagocytosis and survival in
      macrophages are important determinants of parasite virulence. Macrophage lines
      differ dramatically in their ability to sustain intracellular Leishmania infantum
      chagasi (Lic). We report that the U937 monocytic cell line supported the
      intracellular replication and cell-to-cell spread of Lic during 72 h after
      parasite addition, whereas primary human monocyte-derived macrophages (MDMs) did
      not. Electron microscopy and live cell imaging illustrated that Lic promastigotes
      anchored to MDMs via their anterior ends and were engulfed through symmetrical
      pseudopods. In contrast, U937 cells bound Lic in diverse orientations, and
      extended membrane lamellae to reorient and internalize parasites through coiling
      phagocytosis. Lic associated tightly with the parasitophorous vacuole (PV)
      membrane in both cell types. PVs fused with LAMP-1-expressing compartments 24 h
      after phagocytosis by MDMs, whereas U937 cell PVs remained LAMP-1 negative. The
      expression of one phagocytic receptor (CR3) was higher in MDMs than U937 cells,
      leading us to speculate that parasite uptake proceeds through dissimilar pathways
      between these cells. We hypothesize that the mechanism of phagocytosis differs
      between primary versus immortalized human macrophage cells, with corresponding
      differences in the subsequent intracellular fate of the parasite.

PMID- 21723412
TI  - Chinchilla laniger can be used as an experimental model for Taenia solium
      taeniasis.
AB  - Chinchilla laniger has been reported as an experimental definitive host for
      Taenia solium; however no information about its suitability and yield of gravid
      tapeworm proglottids containing viable and infective eggs has been published. In
      total 55 outbred female chinchillas were infected with 4 cysticerci each; hosts
      were immunodeppressed with 6 or 8 mg of methyl-prednisolone acetate every 14 days
      starting the day of infection and their discomfort was followed. Kinetics of
      coproantigen ELISA or expelled proglottids was used to define the infection
      status. Efficiency of tapeworm establishment was 21% and of parasite gravidity
      was 8%; chinchillas showed some degree of suffering along the infection.
      Viability of eggs obtained from gravid proglottids was tested comparing methods
      previously published, our results showed 62% viability with propidium iodide, 54%
      with trypan blue, 34% with neutral red, 30% by oncosphere activation and 7% with
      bromide 3-(4,5-dimetil-tiazol-2-il)-2,5-difenil-tetrazolio (MTT) reduction; no
      statistical differences were obtained between most techniques, except activation.
      Four piglets were infected with 50,000 eggs each, necropsy was performed 3 months
      later and, after counting the number of cysticerci recovered, the percentage of
      infection was similar to data obtained with T. solium eggs recovered from humans.
      Our results demonstrate that the experimental model of T. solium taeniasis in C.
      laniger is a good alternative for providing eggs and adult tapeworms to be used
      in different types of experiments; optimization of the model probably depends on
      the use of inbred hosts and on the reduction of infected animals' suffering.

PMID- 21723413
TI  - Effects of 5 rounds of mass drug administration with diethylcarbamazine and
      albendazole on filaria-specific IgG4 titers in urine: 6-year follow-up study in
      Sri Lanka.
AB  - ELISA for filaria-specific IgG4 in urine (urine ELISA) was applied to children in
      7 schools in Sri Lanka, before and after 5 rounds of annual mass drug
      administration (MDA). The pre-treatment IgG4 prevalence in 2002 was 3.20%, which
      decreased to 0.91% in 2003 after the first MDA (P<0.001), and finally to 0.36% in
      2007 after the 5th MDA. Among 5-10 year-old children, the prevalence decreased
      from 3.37% in 2002 to 0.51% in 2003 (P=0.009). A pattern of IgG4 titer
      distribution according to age and its yearly change could also provide useful
      information in drug efficacy analysis. In 2008, new samples from eleven 2006/07
      urine ELISA-positive students and their family members (total n=56) were examined
      by ICT antigen test, microfilaria test, and urine ELISA. No infection was
      confirmed among them. Urine ELISA will be useful in monitoring
      elimination/resurgence in a post-MDA low endemic situation.

PMID- 21723414
TI  - Studies on the anorectic effect of N-acylphosphatidylethanolamine and
      phosphatidylethanolamine in mice.
AB  - N-acyl-phosphatidylethanolamine is a precursor phospholipid for anandamide,
      oleoylethanolamide, and other N-acylethanolamines, and it may in itself have
      biological functions in cell membranes. Recently, N-palmitoyl
      phosphatidylethanolamine (NAPE) has been reported to function as an anorectic
      hormone secreted from the gut and acting on the brain (Gillum et al., [5]). In
      the current study, two of our laboratories independently investigated whether
      NAPE metabolites may be involved in mediating the anorectic action of NAPE i.p.
      injected in mice. Thus, the anorectic activity of a non-hydrolysable NAPE
      analogue, having ether bonds instead of ester bonds at sn1 and sn2 was compared
      with that of NAPE in molar equivalent doses. Furthermore, the anorectic effect of
      NAPE in NAPE-hydrolysing phospholipase D knockout animals was investigated. As
      negative controls, the NAPE precursor phosphatidylethanolamine and the related
      phospholipids phosphatidylcholine and phosphatidic acid were also tested. All
      compounds except one were found to inhibit food intake, raising the possibility
      that the effect of NAPE is non-specific.

PMID- 21723415
TI  - FMR1 intron 1 methylation predicts FMRP expression in blood of female carriers of
      expanded FMR1 alleles.
AB  - Fragile X syndrome (FXS) is caused by loss of the fragile X mental retardation
      gene protein product (FMRP) through promoter hypermethylation, which is usually
      associated with CGG expansion to full mutation size (>200 CGG repeats).
      Methylation-sensitive Southern blotting is the current gold standard for the
      molecular diagnosis of FXS. For females, Southern blotting provides the
      activation ratio (AR), which is the proportion of unmethylated alleles on the
      active X chromosome. Herein, we examine the relationship of FMRP expression with
      methylation patterns of two fragile X-related epigenetic elements (FREE) analyzed
      using matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry and the AR. We showed that the differential methylation of the FREE2
      sequence within fragile X mental retardation gene intron 1 was related to
      depletion of FMRP expression. We also show that, using the combined cohort of 12
      females with premutation (55 to 200 CGG repeats) and 22 females with full
      mutation alleles, FREE2 methylation analysis was superior to the AR as a
      predictor of the proportion of FMRP-positive cells in blood. Because matrix
      assisted laser desorption/ionization-time-of-flight mass spectrometry is amenable
      to high-throughput processing and requires minimal DNA, these findings have
      implications for routine FXS testing and population screening.

PMID- 21723416
TI  - Uses and abuses of JAK2 and MPL mutation tests in myeloproliferative neoplasms a
      paper from the 2010 William Beaumont hospital symposium on molecular pathology.
AB  - JAK2V617F is sufficiently prevalent in BCR-ABL1-negative myeloproliferative
      neoplasms (MPNs) to be useful as a clonal marker. JAK2V617F mutation screening is
      indicated for the evaluation of erythrocytosis, thrombocytosis, splanchnic vein
      thrombosis, and otherwise unexplained BCR-ABL1-negative granulocytosis. However,
      the mutation does not provide additional value in the presence of unequivocal
      morphologic diagnosis, and its presence does not necessarily distinguish one MPN
      from another or provide useful prognostic information. In general, quantitative
      cell-based JAK2V617F mutation assays are preferred because the additional
      information obtained on mutant allele burden enhances diagnostic certainty and
      facilitates monitoring of response to treatment. JAK2 exon 12 mutation screening
      is indicated only in the presence of JAK2V617F-negative erythrocytosis that is
      associated with a subnormal serum erythropoietin level. MPL mutations are neither
      frequent nor specific enough to warrant their routine use for MPN diagnosis, but
      they may be useful in resolving specific diagnostic problems. The practice of en
      bloc screening for JAK2V617F, JAK2 exon 12, and MPL mutations is scientifically
      irrational and economically irresponsible.

PMID- 21723417
TI  - Sensitive detection and quantification of the JAK2V617F allele by real-time PCR
      blocking wild-type amplification by using a peptide nucleic acid oligonucleotide.
AB  - A single G-to-T missense mutation in the gene for the JAK2 tyrosine kinase,
      leading to a V617F amino acid substitution, is commonly found in several
      myeloproliferative neoplasms. Reliable quantification of this mutant allele is of
      increasing clinical and therapeutic interest in predicting and diagnosing this
      group of neoplasms. Because JAK2V617F is somatically acquired and may be followed
      by loss of heterozygosity, the percentage of mutant versus wild-type DNA in blood
      can vary between 0% and almost 100%. Therefore, we developed a real-time PCR
      assay for detection and quantification of the low-to-high range of the JAK2V617F
      allele burden. To allow the assay to meet these criteria, amplification of the
      wild-type JAK2 was blocked with a peptide nucleic acid oligonucleotide. JAK2V617F
      patient DNA diluted in JAK2 wild-type DNA could be amplified linearly from 0.05%
      to 100%, with acceptable reproducibility of quantification. The sensitivity of
      the assay was 0.05% (n = 3 of 3). In 9 of 100 healthy blood donors, a weak
      positive/background signal was observed in DNA isolated from blood, corresponding
      to approximately 0.01% JAK2V617F allele. In one healthy individual, we observed
      this signal in duplicate. The clinical relevance of this finding is not clear. By
      inhibiting amplification of the wild-type allele, we developed a sensitive and
      linear real-time PCR assay to detect and quantify JAK2V617F.

PMID- 21723418
TI  - Rapid assessment of the heterogeneous methylation status of CEBPA in patients
      with acute myeloid leukemia by using high-resolution melting profile.
AB  - Epigenetic inactivation of tumor-suppressor genes, often in association with
      aberrant DNA methylation of CpG islands in the promoter region of these genes, is
      a key factor in tumorigenesis. CCAAT/enhancer binding protein alpha (CEBPA)
      methylation is a favorable prognostic biomarker for acute myeloid leukemia;
      however, rather than the complete methylation observed in inherited disorders,
      CEBPA methylation is heterogeneous. In this study, we established an algorithm
      called the "methylation index," deduced from high-resolution melting profiles,
      which includes Tm shifting (DeltaTm) and Tm width ratio (fold of width), to
      evaluate the heterogeneous methylation status. The methylation index was highly
      correlated with the exact methylation levels detected by using the MassARRAY
      method (R(2) = 0.80; P < 0.001). Within-run reproducibility for the methylation
      index was 0.9% as the coefficient of variation, and between-run reproducibility
      was 2.6%. It was determined that with a cutoff methylation index of 1.412, the
      best measures of sensitivity and specificity could be obtained (97.14% and
      95.89%, respectively) to discern low or high CEBPA methylation status. This novel
      algorithm for calculation of the methylation index from high-resolution melting
      profiles for CEBPA methylation is compatible with measurement of the methylation
      level as assayed using MassARRAY and could be a simple and efficient screening
      method for determination of CEBPA methylation status in acute myeloid leukemia.

PMID- 21723419
TI  - The toxicity and physiological effects of copper on the freshwater pulmonate
      snail, Lymnaea stagnalis.
AB  - Several recent studies have demonstrated that the freshwater pulmonate snail
      Lymnaea stagnalis is extremely sensitive to metals (Co, Ni, Pb) in chronic
      exposures. The objective of the current study was to evaluate the acute and
      chronic sensitivity of L. stagnalis to Cu and investigate the underlying
      mechanism(s) of toxic action. A 96-h LC50 of 31MUg L(-1) Cu was estimated
      indicating L. stagnalis was moderately acutely sensitive to Cu relative to other
      aquatic organisms. However, in a 30-day chronic exposure using juvenile snails an
      EC20 of 1.8MUg L(-1) Cu was estimated for snail growth making L. stagnalis the
      most sensitive organism tested to date for Cu. Hardness-based and BLM-based water
      quality criteria for Cu at the water quality conditions used in this study were
      7.8 and 1.5MUg L(-1), respectively, indicating L. stagnalis is significantly
      under-protected by hardness-based WQC. Investigations into the mechanism(s) of
      toxic action for Cu were conducted on young adult snails necessitating higher Cu
      exposures. Exposure to Cu at 12MUg L(-1) resulted in no detectable effects on
      hemolymph osmolality, net Ca(2+) uptake, titratable acid excretion, or ammonia
      excretion. Exposure to 48MUg L(-1) Cu was shown to significantly reduce (91%) net
      Ca(2+) uptake which is strongly correlated with shell deposition and
      corresponding snail growth. Snails exposed to 48MUg L(-1) Cu also exhibited
      reduced ammonia excretion, a marked hemolymph acidosis, and a compensatory
      increase in titratable acid excretion. The reduction in net Ca(2+) uptake was
      hypothesized to be a secondary effect of Cu-induced inhibition of carbonic
      anhydrase, but no reduction in carbonic anhydrase activity was detected. Overall,
      it remains unclear whether inhibition of Ca(2+) uptake is a direct result of Cu
      exposure or, along with the other observed physiological effects, is secondary to
      an unidentified primary mode of toxic action. Given the hypersensitivity of L.
      stagnalis to Cu, further study into the mechanisms of action and effects of
      varying water chemistry on Cu toxicity is clearly warranted.

PMID- 21723420
TI  - High-resolution MIRU-VNTRs typing reveals the unique nature of Mycobacterium
      tuberculosis Beijing genotype in Okinawa, Japan.
AB  - Mycobacterium tuberculosis Beijing lineage is highly prevalent in Japan. The aim
      of the present study was to describe the population structure of the Beijing
      lineage in this country based on 12-, 15-, and 21-loci MIRU-VNTR genotyping
      schemes. The MIRU-VNTR patterns of Beijing strains from Okinawa, Ryukyu Islands
      were compared to those recently published from the Osaka-Kobe megalopolis of the
      main island of Japan, Honshu (Wada et al., 2009). We also compared proportions of
      "modern/typical" vs. "ancient/atypical" Beijing strains as defined by structure
      of the NTF locus. Contrarily to the 12-loci Minimum Spanning Tree (MST), the 15-
      and 21-loci trees allowed the distinction of two groups of strains in Okinawa. A
      12-loci MIRU-VNTR pattern (223325173533) corresponding to MIRU international type
      MIT17 was identified as the most prevalent Beijing genotype in Japan. In the
      SITVIT2 database, this pattern was found to be disseminated worldwide and
      corresponded to the most widely distributed Beijing profile in East Asia and
      former USSR countries. A comparison of 15- and 21-loci MIRU-VNTR patterns showed
      that two loci (QUB-4156 and Mtub21) were most polymorphic in our study, and could
      be potential candidates to distinguish between NTF locus based subclassification
      of Beijing strains. High-resolution VNTR typing using 15- and 21-loci underlined
      an evolutionarily distinct "ancient/atypical" subpopulation of the Beijing
      genotype in Okinawa as well as a subgroup of strains closely related to
      "modern/typical" Beijing strains observed in Osaka/Kobe.

PMID- 21723421
TI  - Microsatellite is an important component of complete hepatitis C virus genomes.
AB  - Microsatellites are common and play diverse roles in eukaryotic and prokaryotic
      genomes. However, to our knowledge, microsatellite distribution remains largely
      enigmatic in viruses yet is crucial for understanding instability of viral
      genomes. We have therefore, examined microsatellite distribution in 54 complete
      genomes of Hepatitis C virus (HCV) from six genotypes, showing microsatellites
      were an important component of HCV genomes. Our results showed, in all analyzed
      HCV genomes, genome size and GC content had a weak influence on number, relative
      abundance and relative density of microsatellites, respectively. For each HCV
      genome, mono-, di- and trinucleotide repeats were very predominant, whereas other
      types of repeats rarely occurred. Our results revealed that the occurrence of
      microsatellites was significantly less than higher prokaryotes and eukaryotes and
      that all identified microsatellites were very short. The discovery of
      microsatellites in HCV genomes may become useful for population genetic,
      evolutionary analysis and strain (isolate) identification.

PMID- 21723422
TI  - Overview of errors in the reference sequence and annotation of Mycobacterium
      tuberculosis H37Rv, and variation amongst its isolates.
AB  - Since its publication in 1998, the genome sequence of the Mycobacterium
      tuberculosis H37Rv laboratory strain has acted as the cornerstone for the study
      of tuberculosis. In this review we address some of the practical aspects that
      have come to light relating to the use of H37Rv throughout the past decade which
      are of relevance for the ongoing genomic and laboratory studies of this pathogen.
      These include errors in the genome reference sequence and its annotation, as well
      as the recently detected variation amongst isolates of H37Rv from different
      laboratories.

PMID- 21723423
TI  - Epidemic population structure of extraintestinal pathogenic Escherichia coli
      determined by single nucleotide polymorphism pyrosequencing.
AB  - We have developed an MLST-based scheme for typing Escherichia coli isolates using
      pyrosequencing of single nucleotide polymorphic positions (SNP). The SNP
      sequences are converted into allelic patterns and analyzed using the same
      approach used for MLST analyses. We have tested the method in two unselected
      collections of clinical isolates of E. coli obtained from blood and urine
      cultures. The two collections had a similar structure, 25% of the profiles
      (representing 68% of the isolates) were common to both, and 62% of the profiles
      (nearly 20% of the isolates) were unique. The four major profiles accounted for
      44% of the isolates, and among these the most frequent one was related to the
      pandemic ST131 clone. The method is easy to implement and might be useful for
      typing large microbial collections.

PMID- 21723424
TI  - A polysaccharide from Strongylocentrotus nudus eggs protects against
      myelosuppression and immunosuppression in cyclophosphamide-treated mice.
AB  - To assess the chemoprotective properties of a polysaccharide from
      Strongylocentrotus nudus eggs (SEP), myelosuppressed and immunosuppressed mouse
      models were generated by administration of cyclophosphamide (Cy) and then treated
      with SEP. SEP (16 mg/kg/d) remarkably increased spleen and thymus indices,
      activated the proliferation of leukocytes and erythrocytes and platelets from
      peripheral blood, and exhibited co-mitogenic activity on ConA- or LPS-stimulated
      splenocytes in a dose-dependent manner. An increased percentage of CD34(+) cells
      in bone marrow of Cy-treated mice was also observed. Furthermore, SEP elevated
      CD4(+) T lymphocyte counts as well as the CD4/CD8 ratio dose-dependently, and it
      increased interleukin-2 (IL-2), IgA, IgM, and IgG levels in the sera of Cy
      treated mice. Pre-incubation with TLR2 and TLR4 blocking antibodies inhibited
      splenocyte proliferation and its IL-2 secretion. Finally, SEP significantly
      induced Akt phosphorylation in splenocytes from Cy-treated mice, suggesting that
      chemoprotection by SEP was mediated through the PI3K/Akt signaling pathway. These
      findings indicate that SEP plays an important role in the protection against
      myelosuppression and immunosuppression in Cy-treated mice and could be a
      potential immunomodulatory agent.

PMID- 21723425
TI  - Bioinformatic strategies for unambiguous identification of prostate specific
      antigen in clinical samples.
AB  - Prostate specific antigen (PSA), as a widely used clinical biomarker in prostate
      cancer diagnostics, exists in multiple molecular forms. However, all of these
      forms might not be recognized in a given sample by the standard immunoassays.
      Therefore, we have investigated PSA isoforms, separated by size, using mass
      spectrometric analyses. The objective of these developments was to identify and
      specify the various forms of PSA. To optimize successful identification of
      different PSA forms, we have developed a bioinformatic strategy, consisting of
      high resolution MALDI-MS PMF and sequencing MS/MS data searches. To improve
      sequence-based identification, the recently introduced Proteios software
      environment was employed, allowing the combination of multiple database search
      engines in an automated manner. We could unambiguously identify PSA in clinical
      samples by all detectable tryptic peptides, which were found to be common in
      several isoforms.

PMID- 21723426
TI  - Docosohaexanoic acid-supplemented PACA44 cell lines and over-activation of Krebs
      cycle: an integrated proteomic, metabolomic and interactomic overview.
AB  - Recent investigations have pointed out the ability of fatty acids, in particular
      of docosohaexanoic acid (DHA), to induce growth inhibition and apoptosis in the
      human PaCa-44 pancreatic cancer cell line through a series of mechanisms which
      has been hypothesized to mimic apoptosis. While preliminary evidences indicated
      the involvement of lipid-targeting oxidative stress in DHA-induced apoptotic
      processes, mainly through the alteration of the glutathione (GSH) homeostasis and
      oxidized-glutathione (GSSG) turn-over through their extra-cellular extrusion, no
      further molecular data have been hitherto accumulated. To this end, we hereby
      propose simultaneous protein-targeting and metabolite-oriented analyses, which
      have been integrated through the auxilium of in silico elaboration of those
      protein-protein interaction pathways and enrichment of biological/molecular
      functions. To determine the most suitable time window for the early onset of the
      DHA-triggered apoptosis phenomena we performed flow cytometry-based apoptotic
      assessment at 24, 48 and 72 h. Results indicated that the focus of apoptosis
      onset ranged from 48 to 72 h. From these analyses it emerges that the metabolism
      of control human PaCa-44 pancreatic cancer cell line mainly leans on glycolytic
      pathways, while it is promptly switched to Kreb's cycle activation
      (overexpression of Kreb's cycle enzymes in DHA-treated cells against controls)
      and modulation of the GSH homeostasis through an increased production of GSSG
      reducing NADPH coenzyme via the shift of the glycolytic energy flux towards the
      pentose phosphate pathway. Interestingly, it also emerges a role for structural
      protein alteration in DHA-treated cells, which might be linked to cytoskeletal
      alterations occurring during apoptosis.

PMID- 21723427
TI  - Knee loading stimulates healing of mouse bone wounds in a femur neck.
AB  - Healing of bone wounds is sensitive to various environmental stimuli. Using knee
      loading, which has been shown to stimulate bone formation in mouse femora and
      tibiae, we addressed a question: Does knee loading accelerate a closure of open
      wounds in a femur neck? A surgical wound (0.5 mm in diameter) was generated at
      the femur neck in the left and right femora of C57/BL/6 female mice, and knee
      loading was applied to the left knee for 3 min/day for 3 consecutive days.
      Surgical holes at the femoral midshaft were used as control. Animals were
      sacrificed 1, 2, and 3 weeks after surgery for analyses with MUCT and pQCT as
      well as mechanical testing. The results showed load-driven acceleration of the
      closure of surgical holes. Compared to a sham-loaded contralateral control, knee
      loading reduced the size of surgical wounds in the femoral midshaft by 14%
      (p<0.05), 21% (p<0.01), and 32% (p<0.001) in 1, 2, and 3 weeks, respectively. It
      also decreased the wound size in the femur neck by 16% (p<0.001; 1 week), 18%
      (p<0.001; 2 weeks), and 21% (p<0.001; 3 weeks). Images with pQCT revealed that
      bone mineral density (BMD) was increased from 571+/-19 mg/cm(3) (control) to
      686+/-19 mg/cm(3) (loaded) (p<0.01), and bone mineral content (BMC) from 3.05+/
      0.12 mg/mm (control) to 3.42+/-0.11 mg/mm (loaded) (p<0.05). Furthermore,
      mechanical testing showed that stiffness of the femur was increased by knee
      loading (p<0.05). This study demonstrates that knee loading is capable of
      accelerating healing of surgical wounds throughout the femur including the
      femoral midshaft and neck.

PMID- 21723428
TI  - Bone mineral density is cross sectionally associated with cartilage volume in
      healthy, asymptomatic adult females: Geelong Osteoporosis Study.
AB  - INTRODUCTION: The association between osteoporosis and osteoarthritis (OA) is
      controversial. Although previous studies have shown total body, lower limb,
      spinal and knee BMD and knee cartilage volume to be positively associated, the
      relationship between other distant site-specific measures of BMD and other knee
      structures is unknown. The aim of this study was to determine the associations
      between BMD at eight skeletal sites, and knee structure in asymptomatic young to
      middle-aged females without any clinical signs of OA. METHODS: One hundred and
      sixty healthy, asymptomatic females (29-50 yr) underwent magnetic resonance
      imaging of the knee. BMD was measured at the spine, hip, total body and forearm
      by dual energy X-ray absorptiometry, and at the calcaneus by quantitative
      ultrasound. BMD was tested for an association with cartilage volume, defects, and
      bone marrow lesions (BMLs). RESULTS: Medial cartilage volume was positively
      associated with BMD at the spine, total body, femoral neck, and Ward's triangle
      (all p<0.05), with non-significant associations in the same direction at the
      trochanter (p=0.07). Findings in the lateral compartment were similar. The
      presence of medial cartilage knee defects were also associated with BMD at the
      spine; defects in the lateral compartment were associated with BMD at the forearm
      (both p=0.05). BMD was not associated with the presence of BMLs. No associations
      were observed with calcaneus BMD. CONCLUSIONS: Site-specific BMD is associated
      with cartilage volume at the knee in asymptomatic young to middle-aged adults,
      with the direction and effects trending in the same direction. The magnitude of
      changes correlates with clinically relevant changes. QUS defined calcaneus BMD,
      showed no associations with knee structure. Although systemic factors may
      underlie the association between knee cartilage volume and axial/lower limb BMD,
      these data suggest that common local, possibly biomechanical factors may also
      play a role.

PMID- 21723429
TI  - The relationship between sex steroids, bone turnover and vertebral fracture
      prevalence in asymptomatic men.
AB  - OBJECTIVE: To examine the association between oestradiol (E2), testosterone (T),
      SHBG levels and vertebral fractures' (VFs) prevalence in asymptomatic men.
      METHODS: The study cohort consists of a population of 112 consecutive men (mean+/
      SD (range) age, weight and BMI were 62.9+/-9.2 (41-84) years, 75.0+/-13.8 (45
      120) kgs and 26.4+/-4.7 (18.0-39.6) kg/m(2), respectively). Lateral vertebral
      fracture assessment (VFA) images and scans of the lumbar spine and proximal femur
      were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined
      using a combination of Genant semiquantitative approach and morphometry. Serum
      levels of T, E2, CTx and osteocalcine were measured. Free androgen index (FAI)
      and free estradiol index (FEI) were calculated respectively from the ratio of
      serum T and E2 to SHBG. RESULTS: Among the 112 men, 38 (33.9%) had densitometric
      osteoporosis, and on VFA, VFs were identified in 60 (53.5%): 24 men had grade 1
      and 36 had grade 2 or 3 VFs (32.1%). Men with VFs weighted less and had a
      statistically significant lower lumbar spine and total hip BMD and T-scores than
      those without a VFA-identified vertebral fracture. Levels of osteocalcine, CTx,
      and SHBG were statistically higher in men with grades 2 and 3 VFs than men with
      grade 1 VFs and those without VFs whereas FAI and FEI levels were significantly
      lower. Comparison of patients according to quartiles of SHBG levels showed that
      men in the highest quartile were older, had a lower lumbar spine and total hip
      BMD and a higher prevalence of osteoporosis and VFs. They had also higher levels
      of CTx. Stepwise regression analysis showed that the osteoporotic status and SHBG
      was independently associated to the presence of VFs. CONCLUSION: Men with
      asymptomatic densitometric VFs have lower BMD than subjects without VFs. They
      have evidence of higher SHBG levels and hence lower free sex steroids as well as
      increased bone resorption. This study confirms that BMD and CTx are the most
      important determinant of asymptomatic VFs, and that SHBG is an independent risk
      factor that must be taken into account.

PMID- 21723436
TI  - Carbohydrates as ligands: synthetic and biological aspects.

PMID- 21723437
TI  - Probabilistic models of cognitive development: towards a rational constructivist
      approach to the study of learning and development.

PMID- 21723439
TI  - The null hypothesis: closing the gap between good intentions and good studies.
AB  - Some papers appearing in the two leading clinical journals of our specialty have
      fundamental defects in design, statistical analysis, and reporting. Actual
      publications are used to illustrate what investigators should and should not do,
      from initial planning through to their finished manuscript. A more detailed
      discussion of the most common statistical methods used in reproductive research
      is given as an online supplement. Some of these deficiencies illustrate the
      importance of registry of all study parameters for randomized clinical trials, a
      process covered in greater detail in an accompanying review and required for
      those manuscripts to be considered. Authors and reviewers need to be more aware
      of these requirements and common errors and pitfalls so that only quality
      manuscripts are published.

PMID- 21723440
TI  - A meta-analysis of meta-analyses.
AB  - Meta-analyses have become an increasingly popular method of drawing conclusions
      when there are multiple publications addressing a particular topic. While the
      statistical calculations are straightforward, many of the decisions regarding the
      research question, populations of interest, and inclusion/exclusion criteria are
      subjective and have a significant impact on the conclusions. Readers must
      understand the objective and subjective components of meta-analysis to properly
      evaluate these types of analyses.

PMID- 21723441
TI  - What is the best frame rate for evaluation of sperm motility in different species
      by computer-assisted sperm analysis?
AB  - OBJECTIVE: To evaluate the effect of acquisition rate in the computer-assisted
      sperm analysis (CASA) of sperm motility with different kinetic characteristics
      (linearity and track speed) belonging to different species. DESIGN: Prospective
      research study. SETTING: Andrology laboratory of department of applied biology.
      PATIENT(S): Semen samples from human fertile donors, rabbit, bull, and ram.
      INTERVENTION(S): Semen analysis by optical microscopy and sperm motility
      evaluation with the use of CASA. MAIN OUTCOME MEASURE(S): Analysis of sperm
      tracks with a CASA system acquired at different frame rates (FRs) (12-200 Hz).
      RESULT(S): The FR had no effect on the motility rate or on the sperm track
      reconstruction, whereas all the other kinetic values were affected by sampling
      frequency. Sperm with low speed (category b) and/or linear trajectories (category
      a) are less affected by sampling frequency and do not require particularly high
      FR to be correctly evaluated. On the contrary, fast nonlinear sperm (category c)
      would require a very high frequency to fully describe the path. CONCLUSION(S):
      Because all the commercial CASA systems acquire at an FR of 30-60 Hz, an increase
      in FR is required to render the estimation results closer to the "real path"
      mainly for fast nonlinear sperm.

PMID- 21723442
TI  - Comparative study of the psychosocial risks associated with families with
      multiple births resulting from assisted reproductive technology (ART) and without
      ART.
AB  - OBJECTIVE: To determine whether the psychosocial risks associated with multiple
      births are increased as a consequence of the use of assisted reproductive
      technology (ART) in comparison with those not resulting from ART. DESIGN: Cross
      sectional study. SETTING: Fertility units of a university hospital and a private
      hospital. PATIENT(S): Parents of single children and multiples (twins and
      triplets) between 6 months and 4 years of age (n = 636) were divided into two
      groups: those who conceived through ART (n = 265) and those who conceived through
      non-ART (n = 371). INTERVENTION(S): Administration of six scales, in office or by
      mail. MAIN OUTCOME MEASURE(S): Measurement scales of material necessities, social
      stigma, marital satisfaction, perceived stress, depression, quality of life, and
      their subscales. RESULT(S): The analysis of variance, Student's t-test, and
      chi(2)-test were applied. No effect was observed based on the use of ART in the
      psychosocial variables studied. Significant differences were obtained between the
      groups of single (SB) and multiple births (MB) with respect to material
      necessities, social stigma, marital satisfaction, depression, and quality of
      life. CONCLUSION(S): Having more than one child per birth, whether resulting from
      the use of ART or not, increases psychosocial risks for the parents. Assisted
      reproduction centers should include this information with the obstetric and
      neonatal risks, stressing the advantages of having one child per birth.
      Psychosocial risks are not increased as a result of having used ART, but the goal
      of avoiding the repeated use of ART does influence the desire to transfer the
      maximum number of embryos possible. Psychological counseling should be included
      before initiating ART, as well as when a multiple pregnancy is confirmed.

PMID- 21723443
TI  - Racial influence on the polycystic ovary syndrome phenotype: a black and white
      case-control study.
AB  - OBJECTIVE: To estimate racial disparities in the polycystic ovary syndrome (PCOS)
      phenotype between white and black women with PCOS. DESIGN: Case-control study.
      SETTING: Two academic medical centers. PATIENT(S): A total of 242 women not
      taking confounding medications in otherwise good health. INTERVENTION(S):
      Phenotyping during the follicular phase or anovulation after an overnight fast in
      women. MAIN OUTCOME MEASURE(S): Biometric, serum hormones, glycemic and metabolic
      parameters, and body composition by dual-energy x-ray absorptiometry. RESULT(S):
      We studied 77 white and 43 black women with PCOS and 35 white and 87 black
      controls. Black women with PCOS were similar reproductively to white women with
      PCOS. Black women with PCOS had lower levels of serum transaminases, higher high
      density lipoprotein cholesterol levels (mean difference [MD], 18.2 mg/dL; 95%
      confidence intervals [CI], 14.3, 22.1 mg/dL), lower triglyceride levels (MD, 
      43.2 mg/dL; 95% CI, -64.5, -21.9), and enhanced insulinogenic index on the oral
      glucose tolerance test compared with white women with PCOS. Black women with PCOS
      had higher bone mineral density (MD, 0.1 g/cm(2); 95% CI, 0.1, 0.2 g/cm(2)),
      lower percent body fat on dual-energy x-ray absorptiometry (MD, -2.8%; 95% CI, 
      5.1%, -0.5%), and overall a higher quality of life. Although most of these
      findings disappeared when the differences with racially matched controls were
      compared, black women with PCOS compared with black controls had lower estradiol
      levels than white women with PCOS compared with white controls (MD, -12.9 pg/mL;
      95% CI, -24.9, -0.8 pg/mL), higher systolic blood pressure (MD, 9.1 mm Hg; 95%
      CI, 0.8, 17.4 mm Hg), and lower fasting glucose levels (MD, -12.0 mg/dL; 95% CI, 
      22.3, -1.7 mg/dL). CONCLUSION(S): Racial disparities in PCOS phenotype are minor
      and mixed. Future studies should explore if race impacts treatment effects.

PMID- 21723444
TI  - New NICE guideline to improve outcomes for hip fracture patients.

PMID- 21723445
TI  - ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the
      management of dyslipidaemias of the European Society of Cardiology (ESC) and the
      European Atherosclerosis Society (EAS).

PMID- 21723446
TI  - Coronary artery disease in women.

PMID- 21723447
TI  - Microvascular coronary dysfunction in women: pathophysiology, diagnosis, and
      management.
AB  - Women exhibit a greater symptom burden, more functional disability, and a higher
      prevalence of no obstructive coronary artery disease compared to men when
      evaluated for signs and symptoms of myocardial ischemia. Microvascular coronary
      dysfunction (MCD), defined as limited coronary flow reserve and/or coronary
      endothelial dysfunction, is the predominant etiologic mechanism of ischemia in
      women with the triad of persistent chest pain, no obstructive coronary artery
      disease, and ischemia evidenced by stress testing. Evidence shows that
      approximately 50% of these patients have physiological evidence of MCD. MCD is
      associated with a 2.5% annual major adverse event rate that includes death,
      nonfatal myocardial infarction, nonfatal stroke, and congestive heart failure.
      Although tests such as adenosine stress cardiac magnetic resonance imaging may be
      a useful noninvasive method to predict subendocardial ischemia, the gold standard
      test to diagnose MCD is an invasive coronary reactivity testing. Early
      identification of MCD by coronary reactivity testing may be beneficial in
      prognostication and stratifying these patients for optimal medical therapy.
      Currently, understanding of MCD pathophysiology can be used to guide diagnosis
      and therapy. Continued research in MCD is needed to further advance our
      understanding.

PMID- 21723449
TI  - Investigation of vaporized submicron perfluorocarbon droplets as an ultrasound
      contrast agent.
AB  - Acoustically activated submicron droplets of liquid perfluorocarbon are
      investigated as a new class of ultrasound contrast agent. In the liquid state,
      intravascular droplets can extravasate within tumours. Activation is then
      accomplished by using bursts of ultrasound to vaporize the droplets. We use
      acoustical and optical techniques to assess the characteristics of vaporized
      droplets and the resulting microbubbles in vitro, including size, conversion
      threshold, echogenicity and nonlinearity. Under exposure to single 5-50 cycle
      bursts of ultrasound at 7.5 MHz and mechanical index <1.0, droplets with mean
      diameter of 400 nm convert into microbubbles with mean diameter of 1.4 MUm at 1
      ms after vaporization, expanding to 5.6 MUm by 1 s. The growth of microbubbles
      produced by vaporization causes a characteristic time-dependent increase in
      linear and nonlinear echogenicity, enabling selective detection with conventional
      bubble-specific imaging. These results suggest that submicron perfluorocarbon
      droplets, activated in situ, may be a candidate for an extravascular ultrasound
      contrast agent.

PMID- 21723448
TI  - Ultrasound-enhanced rt-PA thrombolysis in an ex vivo porcine carotid artery
      model.
AB  - Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA)
      thrombolysis. In this study, occlusive porcine whole blood clots were placed in
      flowing plasma within living porcine carotid arteries. Ultrasonically induced
      stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged,
      retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 +/-
      3.8 MUg/mL) or plasma with rt-PA and Definity(r) ultrasound contrast agent (0.79
      +/- 0.47 MUL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to
      peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to
      promote and maximize stable cavitation activity by incorporating ultrasound
      quiescent periods that allowed for the inflow of Definity(r)-rich plasma.
      Cavitation was measured with a passive acoustic detector throughout thrombolytic
      treatment. Thrombolytic efficacy was measured by comparing clot mass before and
      after treatment. Average mass loss for clots exposed to rt-PA and Definity(r)
      without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which
      constituted a significant difference (p < 0.0001). Without Definity(r) there was
      no thrombolytic enhancement by ultrasound exposure alone at this pressure
      amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic
      artery, significant loss of endothelium occurred but no correlation was observed
      between arterial tissue damage and treatment type. Acoustic stable cavitation
      nucleated by an infusion of Definity(r) enhances rt-PA thrombolysis without
      apparent treatment-related damage in this ex vivo porcine carotid artery model.

PMID- 21723450
TI  - Ultrasound contrast imaging based on a novel algorithm combined pulse inversion
      with wavelet transform.
AB  - In this article, an ultrasound contrast imaging method that combines the pulse
      inversion technique with wavelet transform has been proposed to enhance the
      contrast between bubbles and surrounding tissues. In this technique, wavelet
      transform is utilized to analyze the correlation between mother wavelet and the
      received echoes from a pair of inverted transmit pulses, respectively. To obtain
      a better correlation, a new mother wavelet named "bubble wavelet" is constructed
      according to the modified Herring equation. Radio-frequency (RF) data were
      acquired from a modified digital diagnostic ultrasound system that transmits two
      identical pulses with opposite polarity. The proposed method was validated by
      simulations. Experiments were performed on an ultrasound flow phantom and results
      showed that the contrast-to-tissue ratio (CTR) was improved by up to 28 dB
      depending on types of mother wavelet, scales and depths, compared with that
      obtained using pulse-inversion-based second-harmonic imaging. Experiments in vivo
      were also conducted out using kidneys of rabbits and results showed that the
      signals of surrounding tissues can be well suppressed compared with that of
      bubbles. The proposed method was compared with the quadratic pulse inversion
      (QPI) imaging on the same set of experimental data. Further improvements might be
      achieved with optimized bubble wavelet and imaging algorithm.

PMID- 21723452
TI  - Visual perception in preterm children: what are we currently measuring?
AB  - Over the past two decades, cerebral visual impairment has been recognized as a
      principal deficit in preterm children, and in particular those with cerebral
      palsy. We review the current knowledge of visual processing deficits in these
      children, and provide an overview of the tools for assessing cerebral visual
      impairment. Commercially available instruments are usually directed at evaluating
      visuospatial skills rather than detecting object recognition difficulties.
      Particularly in children aged 3 years or younger and in children with multiple
      handicaps, cerebral visual impairment is difficult to diagnose. This difficulty
      may be attributable to limitations specific to the instrument, such as a test
      that is inappropriate for age, or to child-specific limitations such as motor
      impairment or speech delay. We therefore include an overview of relevant
      neuroimaging findings reported in these children, focusing on the most recent
      imaging modalities. Novel techniques such as diffusion tensor imaging may provide
      sensitive markers of cerebral visual impairment in situations where clinical
      diagnosis is difficult, and such approaches may allow for early intervention.

PMID- 21723451
TI  - Properties of phantom tissuelike polymethylpentene in the frequency range 20-70
      MHZ.
AB  - Quantitative ultrasound (QUS) has been used to characterize soft tissues at
      ordinary abdominal ultrasound frequencies (2 to 15 MHz) and is beginning
      application at high frequencies (20 to 70 MHz). For example, backscatter and
      attenuation coefficients can be estimated in vivo using a reference phantom. At
      high frequencies, it is crucial that reverberations do not compromise the
      measurements. Such reverberations can occur between the phantom's scanning window
      and transducer components as well as within the scanning window between its
      surfaces. Transducers are designed to minimize reverberations between the
      transducer and soft tissue. Thus, the acoustic impedance of a phantom scanning
      window should be tissuelike; polymethylpentene (TPX) is commonly used because of
      its tissuelike acoustic impedance. For QUS, it is also crucial to correct for the
      transmission coefficient of the scanning window. Computation of the latter
      requires knowledge of the ultrasonic properties, viz, density, speed and
      attenuation coefficients. This work reports values for the ultrasonic properties
      of two versions of TPX over the high-frequency range. One form (TPX film) is used
      as a scanning window on high-frequency phantoms, and at 40 MHz and 22 degrees C
      was found to have an attenuation coefficient of 120 dB/cm and a propagation speed
      of 2093 m/s.

PMID- 21723453
TI  - Ictal electroencephalograms in neonatal seizures: characteristics and
      associations.
AB  - The characteristics of ictal electroencephalograms in 160 neonatal seizures of 43
      babies were correlated with mortality and neurodevelopmental outcomes. Neonatal
      seizures are focal at onset, most frequently temporal, and often occur during
      sleep. Twenty-one percent of babies with seizures died, and 76% of survivors
      manifested neurodevelopmental impairment during 2-6-year follow-up. A low
      amplitude ictal electroencephalogram discharge was associated with increased
      mortality, and a frequency of <2 Hz with increased morbidity. Status epilepticus,
      ictal fractions, multiple foci, and bihemispheric involvement did not influence
      outcomes. Of 160 seizures, 99 exhibited no associated clinical features
      (electrographic seizures). Neonatal seizures with clinical correlates
      (electroclinical seizures) exhibited a higher amplitude and frequency of ictal
      electroencephalogram discharge than electrographic seizures. During
      electroclinical seizures, the ictal electroencephalogram was more likely to
      involve larger areas of the brain and to cross the midline. Mortality and
      morbidity were similar in babies with electroclinical and electrographic
      seizures, emphasizing the need to diagnose and treat both types. Ictal
      electroencephalogram topography has implications for electrode application during
      limited-channel, amplitude-integrated electroencephalograms. We recommend
      temporal and paracentral electrodes. Video electroencephalograms are important in
      diagnosing neonatal seizures and providing useful information regarding ictal
      electroencephalogram characteristics.

PMID- 21723454
TI  - Idiopathic inflammatory myopathies in childhood: a brief review of 27 cases.
AB  - The most common idiopathic inflammatory myopathies in children include juvenile
      dermatomyositis, juvenile polymyositis, and myositis associated with another
      autoimmune disease (overlap myositis). Idiopathic inflammatory myopathies
      manifest different characteristics affecting children. Only a few investigations
      of childhood idiopathic inflammatory myopathies were reported, involving 27
      patients. In addition, clinical findings, serum muscular enzyme levels, results
      of electromyography studies, muscle biopsy features, and treatment responses were
      studied. Seventeen female and 10 male were classified as exhibiting juvenile
      dermatomyositis (n = 19), juvenile polymyositis (n = 6), or overlap myositis (n =
      2). Overlap myositis was associated with systemic sclerosis and systemic
      erythematous lupus. The mean age at onset was 6.1 years for juvenile
      dermatomyositis, 4.9 years for juvenile polymyositis, and 8.5 years for overlap
      myositis. The most common signs included proximal weakness and myalgia. The serum
      creatine kinase level was increased in 48.2% of patients. An electromyography
      study revealed myopathic features in 85% of patients. Muscle biopsies led to
      observations of inflammatory infiltrates with preferential perivascular
      involvement in the juvenile dermatomyositis group, and endomysial involvement in
      the juvenile polymyositis group. Fiber atrophy was predominantly perifascicular
      in the juvenile dermatomyositis group. Treatment with prednisone improved the
      findings in 81.5% of children.

PMID- 21723455
TI  - Prolonged-release melatonin for children with neurodevelopmental disorders.
AB  - Previous studies demonstrated the efficacy and safety of prolonged-release
      melatonin in children and adolescents with neurodevelopmental and behavioral
      disorders. The long-term effectiveness and safety of prolonged-release melatonin
      treatment were assessed in 88 children (42 girls and 46 boys) with
      neurodevelopmental disorders. These patients participated in a compassionate-use
      program with the drug Circadin (2 mg; Neurim Pharmaceuticals, Tel Aviv, Israel)
      in France, and received treatment in the context of regular care by a specialized
      physician. The study involved a structured questionnaire for the parents,
      comprising a combination of multiple-choice and numeric questions addressing
      sleep onset/offset, sleep quality problems, and mood. The dose of melatonin
      ranged from 4-6 mg, and treatment duration ranged from 6-72 months. Within 3
      months, sleep latency with prolonged-release melatonin decreased by 44.0% (P <
      0.001), sleep duration increased by 10.1% (P < 0.001), the number of awakenings
      decreased by 75% (P < 0.001), and sleep quality improved by 75%, compared with
      baseline (P < 0.001). No serious adverse events or treatment-related
      comorbidities were reported. Prolonged-release melatonin remains a safe,
      effective therapy for the long-term treatment of sleep disorders in children with
      neurodevelopmental disorders.

PMID- 21723456
TI  - Cerebrospinal fluid oligoclonal bands in childhood opsoclonus-myoclonus.
AB  - Oligoclonal bands in cerebrospinal fluid reflect local B-cell responses
      associated with various neuroinflammatory disorders. In opsoclonus-myoclonus
      syndrome, cerebrospinal fluid B-cell expansion was demonstrated, but no studies
      of oligoclonal bands are available. In a prospective case-control study of 132
      children (103 with opsoclonus-myoclonus, 29 neurologic control subjects),
      cerebrospinal fluid oligoclonal bands, measured by isoelectric focusing with
      immunofixation, were observed in 35% with opsoclonus-myoclonus and none of the
      control subjects, with the highest frequency in severe cases (56%). In
      oligoclonal band-positive patients, the mean band number was 5 +/- 3 S.D. (range,
      2-10) and the total severity score was significantly higher than in band-negative
      patients, whereas the frequency of CD19(+) B cells, opsoclonus-myoclonus
      duration, neuroblastoma detection, and relapse history did not differ. The
      cerebrospinal fluid immunoglobulin G synthesis rate, immunoglobulin index, and Q
      albumin were normal. In 17 untreated children receiving adrenocorticotropic
      hormone, intravenous immunoglobulins, and rituximab, the number of oligoclonal
      band-positive decreased by 75%, and the mean band count fell by 80%. Oligoclonal
      band detection adds useful information to neuroimmunologic "staging" in
      opsoclonus-myoclonus. However, flow cytometry provides a more sensitive measure
      of B-cell infiltration. Cerebrospinal fluid oligoclonal bands warrant monitoring
      in long-term follow-up studies of disease-modifying drugs for opsoclonus
      myoclonus.

PMID- 21723457
TI  - Retrospective approach to methylenetetrahydrofolate reductase mutations in
      children.
AB  - Methylenetetrahydrofolate reductase reduces methyltetrahydrofolate, a cosubstrate
      in the remethylation of homocysteine, from methylenetetrahydrofolate. Congenital
      defects, hematologic tumors, and intrauterine growth retardation can occur during
      childhood. This study evaluated clinical and laboratory treatment approaches in
      children diagnosed with methylenetetrahydrofolate reductase mutations. Our group
      included 23 boys and 14 girls, aged 103.4 +/- 70.8 months S.D. Clinical findings
      of patients and homocysteine, vitamin B12, folate, hemogram,
      electroencephalography, cranial magnetic resonance imaging, and echocardiography
      data were evaluated in terms of treatment approach. Our patients' findings
      included vitamin B12 at 400.4 +/- 224.6 pg/mL S.D. (normal range, 300-700 pg/mL),
      folate at 10.1 +/- 4.5 ng/mL S.D. (normal range, 1.8-9 ng/mL), and homocysteine
      at 8.4 +/- 4.7 MUmol/L S.D. (normal range, 5.5-17 MUmol/L). Eighty-eight percent
      of patients demonstrated clinical findings. In comparisons involving categorical
      variables between groups, chi(2) tests were used. No relationship was evident
      between mutation type, laboratory data, and clinical severity. All mothers who
      had MTHFR mutations and had babies with sacral dimples had taken folate
      supplements during pregnancy. To avoid the risk of neural tube defects, pregnant
      women with a MTHFR mutation may require higher than normally recommended doses of
      folic acid supplementation for optimum health.

PMID- 21723458
TI  - Intracranial artery dissection in an adolescent with Marfan syndrome.
AB  - Marfan syndrome is an autosomal dominant connective tissue disorder commonly due
      to mutation of the fibrillin-1 (FBN-1) gene that causes disruption of elastic
      fibers in large- and medium-size arteries and predisposes to aneurysm formation
      and arterial dissection. Cardiovascular complications occur in most patients with
      Marfan syndrome, but interestingly, neurovascular complications of Marfan
      syndrome are rare. We present a novel case of an adolescent with Marfan syndrome
      with spontaneous intracranial cerebral artery dissection and ischemic stroke with
      hemorrhagic transformation. This case is novel in that it reports spontaneous
      intracranial dissection in a young patient with Marfan syndrome and highlights
      the rare intrinsic neurovascular complications that can occur in these patients.

PMID- 21723459
TI  - Giant pediatric aneurysmal bone cysts of the occipital bone: case report and
      review of the literature.
AB  - Cranial aneurysmal bone cysts are uncommon. Cranial aneurysmal bone cysts of the
      occipital bone are exceedingly rare. A 2-year-old toddler with this rare cyst
      presented with a large space-occupying lesion of the posterior fossa, with
      cerebellar tonsillar herniation. The patient experienced complete recovery after
      total excision of the lesion. We review the literature regarding this rare
      presentation, and discuss the origin, pathogenesis, pathologic features, imaging
      characteristics, and treatment of cranial aneurysmal bone cysts.

PMID- 21723460
TI  - Balamuthia amebic meningoencephalitis and mycotic aneurysms in an infant.
AB  - Balamuthia amebic encephalitis is rarely reported in infants. To the best of our
      knowledge, amebic encephalitis complicated by a mycotic aneurysm was only
      described once. We report on an 8-month-child with laboratory-confirmed
      Balamuthia mandrillaris meningoencephalitis, complicated by a mycotic aneurysm of
      the middle cerebral artery.

PMID- 21723462
TI  - Reversible diffuse white matter lesion in Alagille syndrome.
AB  - A boy with genetically confirmed Alagille syndrome was incidentally found to
      manifest striking diffuse hyperintensity of the white matter on T(2)-weighted
      cranial magnetic resonance images. He never exhibited signs of hepatic
      encephalopathy. For his progressive liver failure, he underwent a live-donor
      liver transplant at age 2 years, which unexpectedly resulted in a near-complete
      resolution of the diffuse white matter lesion. Reversible white matter lesions
      attributed to cerebral edema were reported in adult patients with liver
      cirrhosis, but not in the pediatric population. The diffuse reversible white
      matter lesion in the present case demonstrated T(2) hyperintensity, coupled with
      restricted diffusion confirmed by apparent diffusion coefficient, and was
      suggestive of etiologies such as ischemia or cytotoxic edema rather than
      vasogenic edema.

PMID- 21723461
TI  - A novel GPR56 mutation causes bilateral frontoparietal polymicrogyria.
AB  - Bilateral frontoparietal polymicrogyria is an autosomal recessive inherited human
      brain malformation with abnormal cortical lamination. The affected cortex appears
      to consist of numerous small gyri, with scalloping of the cortical-white matter
      junction. There are associated white matter, brain stem, and cerebellar changes.
      Affected individuals manifest mental retardation, language impairment, motor
      developmental delay, and seizure disorder. GPR56 is the causative gene. Here we
      report a novel missense mutation of GPR56, E496K, identified in a consanguineous
      pedigree with bilateral frontoparietal polymicrogyria. GPR56 protein is cleaved
      at the G-protein-coupled receptor proteolytic site into an N- and a C-terminal
      fragment, named GPR56(N) and GPR56(C), respectively. E496K is located in
      GPR56(C). Further biochemical studies reveal that this mutation affects GPR56(C)
      cell surface expression similar to the effect of a previously reported mutation,
      R565W. These results provide further insights into how GPR56 mutation causes
      neurologic disease.

PMID- 21723463
TI  - MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha
      deficiency.
AB  - Pyruvate dehydrogenase complex is a key intramitochondrial multienzyme complex
      required for the conversion of pyruvate to acetyl-CoA. Most patients with
      pyruvate dehydrogenase deficiency have a defect in the E1 alpha subunit,
      associated with mutations in the PDHA1 gene. In this report, we submit detailed
      magnetic resonance images in 4 affected female patients with PDHA1 mutations who
      had with severe cortical atrophy, dilated ventricles, and an incomplete corpus
      callosum. In one of these patients, the magnetic resonance imaging pattern
      prompted molecular diagnostic testing when enzymatic testing was normal. We
      underscore that this constellation of features, which may be misdiagnosed as
      periventricular leukomalacia, illustrates a pattern highly suggestive of a
      deficiency of pyruvate dehydrogenase E1 alpha in female patients and should
      trigger appropriate diagnostic investigations.

PMID- 21723464
TI  - Microdeletion of chromosome 15q26.1 in a child with intractable generalized
      epilepsy.
AB  - Chromosomal abnormalities involving deletions and duplications are known to cause
      severe developmental disorders, including mental retardation, dysmorphism, and
      seizures, in children. As the technique of array-based comparative genomic
      hybridization is being applied more frequently in the diagnostic evaluation of
      children with developmental disorders, novel pathologic chromosomal abnormalities
      are being identified. We report the case of a 9-year-old girl with a history of
      pervasive developmental disorder, growth delay, mild dysmorphic features, and
      intractable primary generalized epilepsy with a de novo microdeletion of
      approximately 0.73-0.94 Mb within chromosome 15q26.1. A much larger (5 Mb) but
      overlapping microdeletion has been previously reported in a 30-month-old child
      with similar phenotype including intractable myoclonic epilepsy, growth delay,
      and dysmorphic features. This leads us to propose that a potential candidate gene
      or genes within the deleted region involved in the pathogenesis of some forms of
      generalized intractable epilepsy, previously considered to be idiopathic.

PMID- 21723465
TI  - Angel's trumpet-associated polyneuropathy-is it Guillain-Barre syndrome?

PMID- 21723467
TI  - Hepatic resection for hepatocellular carcinoma with lymph node metastasis:
      clinicopathological analysis and survival outcome.
AB  - OBJECTIVE: Lymph node metastasis (LNM) rarely occurs in hepatocellular carcinoma
      (HCC). Few studies have reported the potential risk factors of LNM and the
      influence of LNM on the progression and prognosis of HCC. The purposes of this
      study were to explore the clinicopathological characteristics of operable HCC
      with LNM and to demonstrate the effects of LNM on HCC prognosis. METHODS: A
      retrospective review of 2,034 HCC patients undergoing surgery from 1982 to 2005
      was performed. The influence of LNM was assessed by clinicopathological factors,
      tumour recurrence, and overall survival. A total of 66 randomly selected patients
      matched for clinicopathological variables were used to analyse the difference in
      survival. RESULTS: A total of 25 patients (1.23%) were reported to have LNM.
      Higher preoperative carcinoembryonic antigen levels (> 10 ng/mL) were
      significantly associated with a higher incidence of LNM than were low
      preoperative carcinoembryonic antigen levels (<= = 10 ng/mL) (15.38%vs. 3.79%, p
      = 0.042). Furthermore, HCC with LNM (N1 disease) was larger in size (mean, 9.44
      vs. 5.85 cm, p = 0.016) and significantly associated with vascular invasion,
      worse histological grade, and nonencapsulation (p = 0.002, < 0.001, and < 0.001,
      respectively). Finally, patients with HCC accompanied by LNM had shorter mean
      disease-free survival and overall survival (p = 0.001 and < 0.001, respectively).
      CONCLUSION: This study identified the worst prognosis of HCC in a population with
      LNM. HCC with LNM tends to be the infiltrating type with larger tumour size (> 5
      cm), presence of microvascular invasion, and worse histological grade. Liver
      resection with lymphadenectomy is possibly beneficial for patients with HCC
      accompanied by LNM.

PMID- 21723468
TI  - Evaluation of diverting ileostomy in laparoscopic low anterior resection for
      rectal cancer.
AB  - BACKGROUND: Diverting ileostomy is believed to mitigate the effects of
      anastomotic complications in low anterior resections (LAR) for rectal cancer.
      However, there are no data about the effects of diverting ileostomy on the
      outcomes of laparoscopic LAR METHODS: We retrospectively reviewed the medical
      records of 77 consecutive rectal cancer patients who had undergone laparoscopic
      LAR with (n = 23) or without (n = 54) diverting ileostomy. The patients' data
      were recorded and supplemented on short-term follow-up visits and included
      standard demographics, operative procedure, location of the cancer, and final
      pathologic diagnosis. We noted length of hospitalisation, complications, and time
      interval from ileostomy creation to closure. Morbidity and mortality were also
      included. RESULTS: Surgical intervention requiring anastomotic leakage occurred
      in three patients who underwent laparoscopic LAR without diverting ileostomy. The
      anastomosis level of patients who underwent laparoscopic LAR with diverting
      ileostomy was significantly lower than that of patients who underwent
      laparoscopic LAR without diverting ileostomy (p < 0.05). CONCLUSION: Anastomosis
      level and total mesorectal excision are the main factors for creation of
      diverting ileostomy in laparoscopic LAR Laparoscopic LAR without diverting
      ileostomy could be selectively performed. Our study provides a basis for further
      prospective randomised studies on the role of diverting ileostomy in LAR.

PMID- 21723469
TI  - Cause and management of recurrent primary spontaneous pneumothorax after
      thoracoscopic stapler blebectomy.
AB  - BACKGROUND: As the number of patients treated by thoracoscopic stapler blebectomy
      increased, the postoperative recurrence rate had risen unexpectedly. We
      retrospectively investigated the cause and management of primary spontaneous
      pneumothorax recurrence after thoracoscopic stapler blebectomy. METHODS: From
      March 1992 to the end of December 2006, thoracoscopic stapler blebectomy was
      performed in 357 patients with primary spontaneous pneumothorax at the Nihon
      University Itabashi Hospital. The causes and management of recurrence were
      investigated in 30 patients with postoperative recurrence based on items such as
      the resurgical observations, preoperative chest computed tomography findings,
      previous operative notes. RESULTS: Among the patients with bilateral
      pneumothorax, young patients exhibited a higher tendency for postoperative
      recurrence. The most common cause was new bulla formation (28 slides, 16 of which
      were apparently related to the staple line and 12 of which were not related to
      the staple line). CONCLUSION: In thoracoscopic stapler blebectomy for primary
      spontaneous pneumothorax, the most common cause of recurrence was new bulla
      formation. It is necessary to establish additional procedures involving either
      the visceral pleura or the parietal pleura to reduce the recurrence rate.

PMID- 21723470
TI  - Learning curve of robotic-assisted radical prostatectomy with 60 initial cases by
      a single surgeon.
AB  - OBJECTIVE: We tracked various proficiency indicators for the learning curve as a
      single Taiwanese surgeon became familiar with robotic-assisted laparoscopic
      radical prostatectomy surgeries by performing 60 initial procedures. METHODS:
      Between December 2005 and December 2007, 60 consecutive patients were classified
      into Group 1 (Cases 1-30) or Group 2 (Cases 31-60). Pre-operative clinical
      characteristics, operative parameters, and postoperative parameters were
      assessed. RESULTS: Pre-operative biopsy Gleason scores were significantly higher
      in Group 2 than in Group 1 (7.03 vs. 6.13, P < 0.01). The vesicourethral
      anastomosis time showed a statistically significant reduction from 46.38 minutes
      in Group 1 to 31 minutes in Group 2 (p < 0.01). The continence rate at 3 months
      in Group 2 was higher than that in Group 1 (97.6%vs. 76.7%, p = 0.052); the mean
      duration to continence was shorter in Group 2 than Group 1 (70.26 +/- 67.37 days
      vs. 39.63 +/- 36.48 days, p = 0.056). Group 2 had shorter postoperative stays
      (3.93 vs. 7.33) and longer durations of Foley catheter removal (9.0 vs. 7.7) than
      Group 1, representing a statistically significant difference (p < 0.01).
      CONCLUSION: After gaining experience by performing an initial 30 robotic-assisted
      laparoscopic radical prostatectomies, the subsequent 30 surgeries established
      proficiency as determined by vesicourethral anastomosis time and early continence
      rate.

PMID- 21723471
TI  - Intra-operative assessment of axillary sentinel lymph nodes by frozen section-an
      observational study of 260 procedures.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the standard treatment
      for patients with invasive breast cancer. Intra-operative frozen section allows
      for the detection of nodal metastases, thereby allowing a simultaneous axillary
      lymph node dissection (ALND) for those patients with nodal metastases. We herein
      report the accuracy of frozen section in the detection of SLN metastases.
      METHODS: Patients with operable breast cancer and clinically negative axillae
      were recruited for SLNB. The SLNs were identified by blue dye, an isotope, or a
      combination. Enlarged lymph nodes that were not SLNs were also excised. All nodes
      were examined by intra-operative frozen section. ALND was performed if frozen
      section was positive. For those without metastases on frozen section, ALND was
      not performed. All lymph nodes underwent further paraffin sectioning with immuno
      histochemical staining. RESULTS: A total of 260 SLNB procedures were performed
      for invasive carcinoma over a 3-year period. The SLN was identified in 93.5% of
      patients. Of the 243 successful procedures, 53 had nodal metastases on frozen
      section. A total of 33 patients had false-negative frozen sections (false
      negative rate, 38.4%), and 97% of them were less than 2 mm in size. The false
      negative rate for macro-metastases, micro-metastases, and isolated tumour
      cells_were 2.4%, 57.7%, and 94.4%, respectively (p < 0.0001). A total of 22
      patients had delayed ALND, and the re-operation rate was 8.5%. CONCLUSION: Frozen
      section was useful for the detection of nodal metastases in the SLNs and allowed
      for ALND to be performed in the same operation. The main failure of frozen
      sections was in the detection of micro-metastases.

PMID- 21723472
TI  - Modified suture technique in a mouse heart transplant model.
AB  - BACKGROUND: The mouse abdominal heart transplantation model is a basic and
      important immunological research model. We developed a technique for placing
      entire everting sutures instead of half inverting and half everting sutures for
      anastomosis between donor and recipients' caval veins. The purpose of this study
      was to evaluate this modified method. METHODS: Each technique was used in 25 mice
      subjected to isogenic abdominal heart transplantation. Recipient operation time,
      graft warm ischaemia time, time of caval anastomosis, and re-beating time were
      recorded. After transplantation, the heartbeat was palpated through the abdominal
      wall once a day for 100 days. RESULTS: Recipient operation time (40.7 +/- 2.5 min
      vs. 44.3 +/- 2.3 min, p < 0.01), cava-caval anastomosis time (8.4 +/- 1.3 min vs.
      12.1 +/- 1.2 min, p < 0.01), and warm ischaemia time were significantly shorter
      (23.4 +/- 1.7 min vs. 27.2 +/- 1.6 min, p < 0.01) with the modified technique. Re
      beating time was 1.2 +/- 0.4 minutes with the modified technique vs. 1.5 +/- 0.5
      minutes (p = 0.04). There was a tendency for less surgical complications in the
      modified group, but there were no differences in survival rates. CONCLUSION: The
      new suturing technique for mouse cardiac transplantation facilitates easier
      anastomosis of the outflow tract, thereby reducing operation, warm ischaemia, and
      re-beating times.

PMID- 21723473
TI  - Supraglottoplasty for laryngomalacia: who will benefit?
AB  - OBJECTIVE: Laryngomalacia is the most common cause of neonatal and infantile
      stridor. The aim of this study was to assess the outcome of surgical intervention
      in children with laryngomalacia. METHODS: Between January 1998 and December 2008,
      15 children with laryngomalacia underwent surgical intervention at the Universiti
      Kebangsaan Malaysia Medical Centre, from which only eight case notes were
      available. These were retrospectively reviewed for demographic data, symptoms,
      comorbidities, operative technique, postoperative recovery, complications, length
      of hospital stay including intensive care unit (ICU) care, and resolution of
      symptoms. RESULTS: Patients consisted of seven males and one female. One patient
      underwent three procedures, resulting in a total of 10 procedures for this study.
      The mean age was 15.6 months (range: 2-39 months). The most common indication for
      surgery was severe stridor resulting in failure to thrive. Intra-operatively, all
      patients were found to have short aryepiglottic folds, and four also had
      redundant arytenoid mucosa. Supraglottoplasty was performed in 10 patients: three
      by cold instruments and seven by laser. Successful extubation was achieved in the
      operating theatre in eight patients while the other two were extubated in the ICU
      on the same day. Postoperative ICU nursing was required in six patients: three
      for up to 3 days, and three for longer periods because of medical problems.
      Resolution of stridor was complete in four patients, partial in one, and no
      difference in five. Two patients defaulted follow-up. There were no postoperative
      complications from the procedures. The average length of follow-up was 15 weeks
      (range: 12 days to 7 years). CONCLUSION: Supraglottoplasty remains an effective
      method to treat severe laryngomalacia. Patients who will benefit most are those
      with severe laryngomalacia that is uncomplicated by neurological conditions or
      multiple medical problems. In our institution, early extubation is the norm, and
      a significant number of patients can be nursed in the normal wards and be
      discharged within 48 hours of the procedure.

PMID- 21723474
TI  - Long-term survivor of primary anorectal malignant melanoma by a multi
      disciplinary approach.
AB  - Anorectal malignant melanoma tends to show an aggressive biological behaviour.
      Therefore, the 5-year survival rate is limited. We herein present a successful
      case of a super-long-term survivor (20 years) who underwent multi-disciplinary
      treatment. The present case suggests that a multi-disciplinary approach may be
      beneficial for patients with thick and extensively sized lesions after radical
      resection for primary anorectal malignant melanoma.

PMID- 21723475
TI  - Salivary gland nocardiosis in an immunocompetent patient.
AB  - We report a case of nocardiosis in an immunocompetent patient who presented with
      pain and multiple swellings in the face. Nocardia asteroides was isolated from
      the parotid and submandibular salivary glands. The patient was successfully
      treated by surgical drainage and oral administration of trimethoprim and
      sulfamethoxazole. To the best of our knowledge, this is the first reported case
      from India on N. asteroides affecting the salivary gland.

PMID- 21723476
TI  - Re: "outsourcing to teleradiology companies: bad for radiology, bad for
      radiologists".

PMID- 21723477
TI  - The national radiology data registry: a necessary component of quality health
      care.

PMID- 21723478
TI  - The continuing saga.

PMID- 21723479
TI  - Helium: impending crisis for radiology, or just more hot air?

PMID- 21723480
TI  - What can bureaucracies teach radiology?

PMID- 21723481
TI  - I can't absorb anymore.

PMID- 21723482
TI  - ACR appropriateness criteria((r)) on abnormal vaginal bleeding.
AB  - In evaluating a woman with abnormal vaginal bleeding, imaging cannot replace
      definitive histologic diagnosis but often plays an important role in screening,
      characterization of structural abnormalities, and directing appropriate patient
      care. Transvaginal ultrasound (TVUS) is generally the initial imaging modality of
      choice, with endometrial thickness a well-established predictor of endometrial
      disease in postmenopausal women. Endometrial thickness measurements of <=5 mm and
      <=4 mm have been advocated as appropriate upper threshold values to reasonably
      exclude endometrial carcinoma in postmenopausal women with vaginal bleeding;
      however, the best upper threshold endometrial thickness in the asymptomatic
      postmenopausal patient remains a subject of debate. Endometrial thickness in a
      premenopausal patient is a less reliable indicator of endometrial pathology since
      this may vary widely depending on the phase of menstrual cycle, and an upper
      threshold value for normal has not been well-established. Transabdominal
      ultrasound is generally an adjunct to TVUS and is most helpful when TVUS is not
      feasible or there is poor visualization of the endometrium. Hysterosonography may
      also allow for better delineation of both the endometrium and focal abnormalities
      in the endometrial cavity, leading to hysteroscopically directed biopsy or
      resection. Color and pulsed Doppler may provide additional characterization of a
      focal endometrial abnormality by demonstrating vascularity. MRI may also serve as
      an important problem-solving tool if the endometrium cannot be visualized on TVUS
      and hysterosonography is not possible, as well as for pretreatment planning of
      patients with suspected endometrial carcinoma. CT is generally not warranted for
      the evaluation of patients with abnormal bleeding, and an abnormal endometrium
      incidentally detected on CT should be further evaluated with TVUS.

PMID- 21723483
TI  - Self-referral in medical imaging: a meta-analysis of the literature.
AB  - PURPOSE: In the current political and economic climate, there is a desire to
      reduce health care costs; diagnostic imaging expenditure is one area of
      particular interest. The authors present a meta-analysis of the relative
      frequency of imaging utilization in the setting of self-referral compared with
      that of non-self-referral and a simulation of increased cost to Medicare Part B
      on the basis of this relative frequency. METHODS: The MEDLINE database was
      searched systematically. Specific inclusion criteria for relative frequency
      calculations were a numerator (number of patients imaged) and denominator (number
      of total patients seen) in each group (self-referrers and radiologist referrers).
      The relative risk of self-referral was determined for each group and is defined
      by the "relative frequency" of imaging utilization for the self-referrers divided
      by the frequency for the radiologist referrers. Relative frequency represents the
      increased (if >1) or decreased (if <1) chance of imaging by self-referrers over
      radiologist referrers. The meta-analysis was used to combine imaging frequencies
      for each referral condition of the individual studies that met inclusion criteria
      for an overall estimate of relative frequency, using a random-effects model to
      account for the variations among the studies. Relative frequency data were then
      used to perform a cost simulation to Medicare Part B using 2006 data. RESULTS:
      The initial search yielded 334 articles, 5 of which met the threshold for
      inclusion. In these 5 studies, 76,905,162 total episodes of care were analyzed.
      The individual relative frequency of imaging in the setting of self-referral
      ranged from 1.60 to 4.50. The combined relative frequency was 2.16 (95%
      confidence interval, 2.15-2.16) using the fixed-effects model and 2.48 (95%
      confidence interval, 1.90-3.24) using the random-effects model. For 2006
      Government Accountability Office (GAO) data, the estimated cost of increased
      imaging in the setting of self-referral was $3.6 billion, but a range of costs
      was also provided to account for potential inaccuracies in the GAO data.
      CONCLUSIONS: The existing literature yields a combined relative frequency of
      imaging of 2.48 (95% confidence interval, 1.90-3.24) for self-referrers compared
      with non-self-referrers. Precise extrapolation of Medicare Part B costs
      attributable to self-referral would require changes in reporting requirements for
      imaging equipment ownership. Cost simulation results total billions of dollars
      annually and may be irrespective of potential inaccuracies in the GAO data as a
      result of Current Procedural Terminology((r)) coding ambiguity and nontransparent
      reporting of equipment ownership.

PMID- 21723484
TI  - Volume of neuroradiology studies read by neurologists: implications for
      fellowship training.
AB  - PURPOSE: The ACGME recognizes radiology's neuroradiology fellowship programs as
      the pathway to neuroradiology expertise. Members of the American Society of
      Neuroimaging have called for the expansion of neuroradiology fellowships for
      neurologists with informal accreditation through the United Council for
      Neurologic Subspecialties. The aim of this study was to investigate the number of
      neuroradiologic studies read by neurologists to assess their capacity to support
      fellowship positions at ACGME training criteria. METHODS: The numbers of
      neuroradiologic studies interpreted by radiologists and neurologists in the
      inpatient and hospital outpatient settings were determined from the CMS
      Physician/Supplier Procedure Summary Master Files for 1996 to 2008. The ACGME
      requirements of 1,500 neuroradiologic CT and 1,500 neuroradiologic MR scans per
      fellow per year were used to calculate the number of fellowship positions that
      could be supported by each specialty. RESULTS: In 2008, in the inpatient and
      hospital outpatient setting, radiologists interpreted 9,287,768 (98.3% of the
      total) and neurologists interpreted 43,107 (0.5% of the total) neuroradiologic
      examinations on Medicare patients. Per ACGME requirements, on the basis of CT
      volumes, radiologists could potentially train 4,256 neuroradiology fellows,
      compared with neurologists' 12 fellows, assuming a single fellow was exposed to
      every Medicare case. On the basis of MR volumes, radiologists and neurologists
      could train 1,935 and 16 fellows, respectively. CONCLUSIONS: Radiologists are
      responsible for interpreting the vast majority (98.3%) of neuroradiologic
      studies. Neurologists have a limited exposure to neuroradiologic CT and MR and
      could support only 12 fellowship positions by ACGME criteria on the basis of
      reading available 1996 to 2008 Medicare cases.

PMID- 21723485
TI  - Placement and removal of inferior vena cava filters: national trends in the
      medicare population.
AB  - PURPOSE: The aim of this study was to evaluate trends in the placement and
      removal of inferior vena cava (IVC) filters in the Medicare population. METHODS:
      Summary Medicare claims data from 1999 through 2008 were used to identify the
      frequency of IVC filter placement procedures by specialty (radiology, surgery,
      cardiology, and all others) and site of service. Claims from 2003 (the first year
      the FDA cleared retrievable labeling for filters) through 2008 were used to
      identify intravascular foreign body retrieval procedures, and modeling was used
      estimate a frequency range of removal procedures. Trends over time were
      evaluated. RESULTS: Between 1999 and 2008, total Medicare fee-for-service
      beneficiary frequency of IVC filter placement procedures increased by 111.5%
      (30,756 to 65,041). Volumes increased for radiologists (16,531 to 36,829
      [+122.8%]), surgeons (11,295 to 22,606 [+100.1%]), and cardiologists (1,025 to
      4,236 [+313.3%]). Relative specialty market shares changed little over time.
      Volumes increased by 114.2% (26,511 to 56,774) and 229.1% (2,286 to 7,524) for
      hospital inpatients and outpatients, respectively, and decreased by 62.1% (1,959
      to 743) for those in all other locations combined. In 2008, with 65,041 filters
      placed, only an estimated 801 to 3,339 (1.2 to 5.1%) were removed. CONCLUSION:
      The frequency of IVC filter placement has doubled over the past decade, and
      radiologists continue to perform more than half of all procedures. Although
      volume has more than tripled in hospital outpatients, the inpatient setting
      remains by far the most common site of service. In the Medicare population, IVC
      filters are not commonly removed.

PMID- 21723486
TI  - Design of site-specific prognostic morbidity-mortality studies and internal
      outcome focus studies in radiation oncology.
AB  - This research focuses on morbidity-mortality reviews and internal outcome focus
      studies. Definitions are provided as well as a complete discussion of the ideal
      parameters to consider when constructing each of these. The implementation of the
      design characteristics used may be of assistance to a center pursuing achievement
      of these requirements toward accreditation to exemplify continuous quality
      improvement in external-beam radiation therapy. The article further provides the
      educational tools necessary for readers to mature expanded studies from it for
      advanced site-specific clinical analyses.

PMID- 21723487
TI  - Just-in-time radiologist decision support: the importance of PACS-integrated
      workflow.
AB  - PURPOSE: Decision support systems for radiologists can provide information during
      image interpretation that may efficiently improve diagnostic accuracy and
      increase radiologists' confidence. However, most decision support systems require
      radiologists to exit PACS, which may deter busy radiologists from pursuing
      decision support. The purpose of this study was to determine whether radiologists
      would use a PACS-integrated decision support tool more frequently than an
      equivalent nonintegrated system. METHODS: Forty-eight radiology residents were
      randomly assigned to one of two groups: the control group was provided access to
      a radiology clinical decision support tool via Web access, which required the
      resident to launch a Web browser from a desktop icon and then log in to the
      decision support application. The experimental group was provided access to the
      same tool but was allowed to launch from a PACS-integrated portal with automated
      login and authentication. Halfway through the 10-month study period, the groups
      were switched. The main outcome measure was the average number of decision
      support sessions initiated each month over the study period. RESULTS: The
      experimental (integrated) group had higher use than the control (nonintegrated)
      group by a factor of 3.0 (P < .05). When integrated access was removed from the
      experimental group, their use fell by 52%. When integrated access was granted to
      the control group, their use rose by only 20%. CONCLUSION: Integration with PACS
      improves radiologists' use of clinical decision support tools. Integrated access
      is critical at the time of initial deployment, or acceptance of the decision
      support tools may be undermined.

PMID- 21723488
TI  - Frequent body CT scanning of young adults: indications, outcomes, and risk for
      radiation-induced cancer.
AB  - PURPOSE: The aims of this study were to define the magnitude of frequent body CT
      scanning of young adults and to determine associated patient diagnoses,
      examination indications, short-term outcomes, and estimated radiation-induced
      cancer risk. METHODS: Patients aged 18 to 35 years who underwent chest or
      abdominopelvic CT between 2003 and 2007 at any of 3 hospitals were identified and
      categorized by total number of scans per body part as rarely (<5), intermediately
      (>5 and <15), or frequently (>15) scanned. Medical records of the frequently
      scanned were reviewed. Cumulative radiation exposure, calculated from typical
      effective doses, was used to estimate cancer risk. Cancer incidence and mortality
      were estimated using the Biological Effects of Ionizing Radiation method.
      RESULTS: A total of 25,104 patients underwent 45,632 scans, of whom 23,851 (95%)
      and 70 (0.3%) were rarely and frequently scanned, respectively. Among frequently
      scanned patients, the most common diagnoses were cancer (19 of 36 [52.8%]) and
      cystic fibrosis with lung transplantation (11 of 36 [30.5%]) for chest CT and
      cancer (25 of 34 [73.5%]) for abdominopelvic CT. During the mean 5.4 years
      (range, 0.9-7.6 years) of follow-up, 46% of frequently scanned patients (32 of
      70) died. Of the 47 cancers predicted in the entire cohort, 36 (77%) and 2 (3%)
      were expected in the rarely and frequently scanned. CONCLUSIONS: The majority of
      CT-induced cancers are predicted to result from sporadic rather than frequent
      scanning. Frequent scanning confers a significant cancer risk but occurs in
      severely ill patients, a large proportion of who die before any radiation-induced
      cancer would be a factor in their health.

PMID- 21723489
TI  - Global quality imaging: emerging issues.
AB  - Quality imaging may be described as "a timely access to and delivery of
      integrated and appropriate procedures, in a safe and responsive practice, and a
      prompt delivery of an accurately interpreted report by capable personnel in an
      efficient, effective, and sustainable manner." For this article, radiation safety
      is considered as one of the key quality elements. The stakeholders are the
      drivers of quality imaging. These include those that directly provide or use
      imaging procedures and others indirectly supporting the system. Imaging is
      indispensable in health care, and its use has greatly expanded worldwide.
      Globalization, consumer sophistication, communication and technological advances,
      corporatization, rationalization, service outsourcing, teleradiology, workflow
      modularization, and commoditization are reshaping practice. This article defines
      the emerging issues; an earlier article in the May 2011 issue described possible
      improvement actions. The issues that could threaten the quality use of imaging
      for all countries include workforce shortage; increased utilization, population
      radiation exposure, and cost; practice changes; and efficiency drive and budget
      constraints. In response to these issues, a range of quality improvement
      measures, strategies, and actions are used to maximize the benefits and minimize
      the risks. The 3 measures are procedure justification, optimization of image
      quality and radiation protection, and error prevention. The development and
      successful implementation of such improvement actions require leadership,
      collaboration, and the active participation of all stakeholders to achieve the
      best outcomes that we all advocate.

PMID- 21723490
TI  - Recruiting junior faculty members/disruptive behavior of a prestigious physician
      scientist.

PMID- 21723491
TI  - Keeping a license to practice: prove it or lose it.

PMID- 21723492
TI  - Educating leaders: a foundation curriculum for radiologists.

PMID- 21723493
TI  - Eight things you need to know about noncompetition covenants.

PMID- 21723494
TI  - Features to consider when selecting new ultrasound imaging systems.

PMID- 21723495
TI  - Robert W. McConnell.

PMID- 21723496
TI  - Saturated fatty acids and snoRNAs: partners in crime.
AB  - Lipotoxicity describes the process of cellular dysfunction in response to lipid
      overload. In this issue of Cell Metabolism, Michel and colleagues (2011) provide
      evidence for a role of snoRNAs in palmitate-induced oxidative stress.

PMID- 21723497
TI  - Inflaming hypothalamic neurons raises blood pressure.
AB  - Obesity and hypertension are strongly associated, and neural dysfunction has been
      implicated in both. The hypothalamus integrates signals regulating blood pressure
      and energy homeostasis. A recent paper in Nature Medicine (Purkayastha et al.,
      2011) suggests that obesity and hypertension are caused by inflammation in
      distinct hypothalamic neuronal populations.

PMID- 21723498
TI  - Islets have a lot of nerve! Or do they?
AB  - The autonomic nervous system influences insulin and glucagon secretion. In this
      issue, Rodriguez-Diaz et al. (2011) show that mouse and human islets differ in
      their innervation patterns, yet the effect of neural activation on islet hormone
      secretion is similar. Key questions raised by this species difference have
      potential relevance to diabetic therapeutics.

PMID- 21723499
TI  - Fluorescent green plaques: light at the end of the catheter?
AB  - The field of vascular molecular imaging is searching for the "holy grail" of an
      imaging technique that will quantitatively and reliably assess vulnerable
      coronary plaques. Fluorescence imaging with indocyanine green specifically
      identifies lipid-rich plaques in rabbits and in humans and represents a
      promising, though invasive, approach.

PMID- 21723500
TI  - Hormonal regulation of hepatic glucose production in health and disease.
AB  - We review mechanisms that regulate production of glucose by the liver, focusing
      on areas of budding consensus, and endeavoring to provide a candid assessment of
      lingering controversies. We also attempt to reconcile data from tracer studies in
      humans and large animals with the growing compilation of mouse knockouts that
      display changes in glucose production. A clinical hallmark of diabetes, excessive
      glucose production remains key to its treatment. Hence, we attempt to integrate
      emerging pathways into the broader goal to rejuvenate the staid antidiabetic
      pharmacopeia.

PMID- 21723501
TI  - Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent
      and independent pathways.
AB  - Through unknown mechanisms, insulin activates the sterol regulatory element
      binding protein (SREBP1c) transcription factor to promote hepatic lipogenesis. We
      find that this induction is dependent on the mammalian target of rapamycin (mTOR)
      complex 1 (mTORC1). To further define the role of mTORC1 in the regulation of
      SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1
      (LTsc1KO), which results in insulin-independent activation of mTORC1.
      Surprisingly, the LTsc1KO mice are protected from age- and diet-induced hepatic
      steatosis and display hepatocyte-intrinsic defects in SREBP1c activation and de
      novo lipogenesis. These phenotypes result from attenuation of Akt signaling
      driven by mTORC1-dependent insulin resistance. Therefore, mTORC1 activation is
      not sufficient to stimulate hepatic SREBP1c in the absence of Akt signaling,
      revealing the existence of an additional downstream pathway also required for
      this induction. We provide evidence that this mTORC1-independent pathway involves
      Akt-mediated suppression of Insig2a, a liver-specific transcript encoding the
      SREBP1c inhibitor INSIG2.

PMID- 21723502
TI  - Small nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic
      stress.
AB  - Lipotoxicity is a metabolic stress response implicated in the pathogenesis of
      diabetes complications and has been shown to involve lipid-induced oxidative
      stress. To elucidate the molecular mechanisms of lipotoxicity, we used retroviral
      promoter trap mutagenesis to isolate a cell line that is resistant to lipotoxic
      and oxidative stress. We show that loss of three box C/D small nucleolar RNAs
      (snoRNAs) encoded in the ribosomal protein L13a (rpL13a) locus is sufficient to
      confer resistance to lipotoxic and oxidative stress in vitro and prevents the
      propagation of oxidative stress in vivo. Our results provide evidence for a
      previously unappreciated, non-canonical role for box C/D snoRNAs as regulators of
      metabolic stress response pathways in mammalian cells.

PMID- 21723503
TI  - Innervation patterns of autonomic axons in the human endocrine pancreas.
AB  - The autonomic nervous system regulates hormone secretion from the endocrine
      pancreas, the islets of Langerhans, thus impacting glucose metabolism. The
      parasympathetic and sympathetic nerves innervate the pancreatic islet, but the
      precise innervation patterns are unknown, particularly in human. Here we
      demonstrate that the innervation of human islets is different from that of mouse
      islets and does not conform to existing models of autonomic control of islet
      function. By visualizing axons in three dimensions and quantifying axonal
      densities and contacts within pancreatic islets, we found that, unlike mouse
      endocrine cells, human endocrine cells are sparsely contacted by autonomic axons.
      Few parasympathetic cholinergic axons penetrate the human islet, and the invading
      sympathetic fibers preferentially innervate smooth muscle cells of blood vessels
      located within the islet. Thus, rather than modulating endocrine cell function
      directly, sympathetic nerves may regulate hormone secretion in human islets by
      controlling local blood flow or by acting on islet regions located downstream.

PMID- 21723504
TI  - Life span extension via eIF4G inhibition is mediated by posttranscriptional
      remodeling of stress response gene expression in C. elegans.
AB  - Reducing protein synthesis slows growth and development but can increase adult
      life span. We demonstrate that knockdown of eukaryotic translation initiation
      factor 4G (eIF4G), which is downregulated during starvation and dauer state,
      results in differential translation of genes important for growth and longevity
      in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition
      of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in
      ribosomal loading and translation of stress response genes. Some of these genes
      are required for life span extension when IFG-1 is inhibited. Furthermore,
      enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated
      with increased mRNA length. This association was supported by changes in the
      proteome assayed via quantitative mass spectrometry. Our results suggest that IFG
      1 mediates the antagonistic effects on growth and somatic maintenance by
      regulating mRNA translation of particular mRNAs based, in part, on transcript
      length.

PMID- 21723505
TI  - Protection from obesity and diabetes by blockade of TGF-beta/Smad3 signaling.
AB  - Imbalances in glucose and energy homeostasis are at the core of the worldwide
      epidemic of obesity and diabetes. Here, we illustrate an important role of the
      TGF-beta/Smad3 signaling pathway in regulating glucose and energy homeostasis.
      Smad3-deficient mice are protected from diet-induced obesity and diabetes.
      Interestingly, the metabolic protection is accompanied by Smad3(-)(/-) white
      adipose tissue acquiring the bioenergetic and gene expression profile of brown
      fat/skeletal muscle. Smad3(-/-) adipocytes demonstrate a marked increase in
      mitochondrial biogenesis, with a corresponding increase in basal respiration, and
      Smad3 acts as a repressor of PGC-1alpha expression. We observe significant
      correlation between TGF-beta1 levels and adiposity in rodents and humans.
      Further, systemic blockade of TGF-beta signaling protects mice from obesity,
      diabetes, and hepatic steatosis. Together, these results demonstrate that TGF
      beta signaling regulates glucose tolerance and energy homeostasis and suggest
      that modulation of TGF-beta activity might be an effective treatment strategy for
      obesity and diabetes.

PMID- 21723506
TI  - In vivo correction of COX deficiency by activation of the AMPK/PGC-1alpha axis.
AB  - Increased mitochondrial biogenesis by activation of PPAR- or AMPK/PGC-1alpha
      dependent homeostatic pathways has been proposed as a treatment for mitochondrial
      disease. We tested this hypothesis on three recombinant mouse models
      characterized by defective cytochrome c-oxidase (COX) activity: a knockout (KO)
      mouse for Surf1, a knockout/knockin mouse for Sco2, and a muscle-restricted KO
      mouse for Cox15. First, we demonstrated that double-recombinant animals
      overexpressing PGC-1alpha in skeletal muscle on a Surf1 KO background showed
      robust induction of mitochondrial biogenesis and increase of mitochondrial
      respiratory chain activities, including COX. No such effect was obtained by
      treating both Surf1(-/-) and Cox15(-/-) mice with the pan-PPAR agonist
      bezafibrate, which instead showed adverse effects in either model. Contrariwise,
      treatment with the AMPK agonist AICAR led to partial correction of COX deficiency
      in all three models, and, importantly, significant motor improvement up to normal
      in the Sco2(KO/KI) mouse. These results open new perspectives for therapy of
      mitochondrial disease.

PMID- 21723507
TI  - Heat shock transcription factor 1 is a key determinant of HCC development by
      regulating hepatic steatosis and metabolic syndrome.
AB  - Hepatocellular carcinoma (HCC) occurrence and progression are linked tightly to
      progressive hepatic metabolic syndrome associated with insulin resistance,
      hepatic steatosis, and chronic inflammation. Heat shock transcription factor 1
      (HSF1), a major transactivator of stress proteins, increases survival by
      protecting cells against environmental stressors. It has been implicated in the
      pathogenesis of cancer, but specific mechanisms by which HSF1 supports cancer
      development remain elusive. We propose a pathogenic mechanism whereby HSF1
      activation promotes growth of premalignant cells and HCC development by
      stimulating lipid biosynthesis and perpetuating chronic hepatic metabolic disease
      induced by carcinogens. Our work shows that inactivation of HSF1 impairs cancer
      progression, mitigating adverse effects of carcinogens on hepatic metabolism by
      enhancing insulin sensitivity and sensitizing activation of AMP-activated protein
      kinase (AMPK), an important regulator of energy homeostasis and inhibitor of
      lipid synthesis. HSF1 is a potential target for the control of hepatic steatosis,
      hepatic insulin resistance, and HCC development.

PMID- 21723508
TI  - Adiponectin is required for PPARgamma-mediated improvement of endothelial
      function in diabetic mice.
AB  - Rosiglitazone is a PPARgamma agonist commonly used to treat diabetes. In addition
      to improving insulin sensitivity, rosiglitazone restores normal vascular function
      by a mechanism that remains poorly understood. Here we show that adiponectin is
      required to mediate the PPARgamma effect on vascular endothelium of diabetic
      mice. In db/db and diet-induced obese mice, PPARgamma activation by rosiglitazone
      restores endothelium-dependent relaxation of aortae, whereas diabetic mice
      lacking adiponectin or treated with an anti-adiponectin antibody do not respond.
      Rosiglitazone stimulates adiponectin release from fat explants, and subcutaneous
      fat transplantation from rosiglitazone-treated mice recapitulates vasodilatation
      in untreated db/db recipients. Mechanistically, adiponectin activates AMPK/eNOS
      and cAMP/PKA signaling pathways in aortae, which increase NO bioavailability and
      reduce oxidative stress. Taken together, these results demonstrate that adipocyte
      derived adiponectin is required for PPARgamma-mediated improvement of endothelial
      function in diabetes. Thus, the adipose tissue represents a promising target for
      treating diabetic vasculopathy.

PMID- 21723509
TI  - Thiazolidinediones regulate adipose lineage dynamics.
AB  - White adipose tissue regulates metabolism; the importance of this control is
      highlighted by the ongoing pandemic of obesity and associated complications such
      as diabetes, atherosclerosis, and cancer. White adipose tissue maintenance is a
      dynamic process, yet very little is known about how pharmacologic stimuli affect
      such plasticity. Combining in vivo lineage marking and BrdU labeling strategies,
      we found that rosiglitazone, a member of the thiazolidinedione class of glucose
      lowering medicines, markedly increases the evolution of adipose progenitors into
      adipocytes. Notably, chronic rosiglitazone administration disrupts the adipogenic
      and self-renewal capacities of the stem cell compartment and alters its molecular
      characteristics. These data unravel unknown aspects of adipose dynamics and
      provide a basis to manipulate the adipose lineage for therapeutic ends.

PMID- 21723510
TI  - Molecular control of systemic bile acid homeostasis by the liver glucocorticoid
      receptor.
AB  - Systemic bile acid (BA) homeostasis is a critical determinant of dietary fat
      digestion, enterohepatic function, and postprandial thermogenesis. However, major
      checkpoints for the dynamics and the molecular regulation of BA homeostasis
      remain unknown. Here we show that hypothalamic-pituitary-adrenal (HPA) axis
      impairment in humans and liver-specific deficiency of the glucocorticoid receptor
      (GR) in mice disrupts the normal changes in systemic BA distribution during the
      fasted-to-fed transition. Fasted mice with hepatocyte-specific GR knockdown had
      smaller gallbladder BA content and were more susceptible to developing
      cholesterol gallstones when fed a cholesterol-rich diet. Hepatic GR deficiency
      impaired liver BA uptake/transport via lower expression of the major hepatocyte
      basolateral BA transporter, Na(+)-taurocholate transport protein (Ntcp/Slc10a1),
      which affected dietary fat absorption and brown adipose tissue activation. Our
      results demonstrate a role of the HPA axis in the endocrine regulation of BA
      homeostasis through the liver GR control of enterohepatic BA recycling.

PMID- 21723511
TI  - 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced
      tumor formation and regression.
AB  - Tumor cells have an altered metabolic phenotype characterized by increased
      glycolysis and diminished oxidative phosphorylation. Despite the suspected
      importance of glycolysis in tumorigenesis, the temporal relationship between
      oncogene signaling, in vivo tumor formation, and glycolytic pathway activity is
      poorly understood. Moreover, how glycolytic pathways are altered as tumors
      regress remains unknown. Here, we use a switchable model of Myc-driven liver
      cancer, along with hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic
      imaging (MRSI) to visualize glycolysis in de novo tumor formation and regression.
      LDHA abundance and activity in tumors is tightly correlated to in vivo pyruvate
      conversion to lactate and is rapidly inhibited as tumors begin to regress, as are
      numerous glycolysis pathway genes. Conversion of pyruvate to alanine predominates
      in precancerous tissues prior to observable morphologic or histological changes.
      These results demonstrate that metabolic changes precede tumor formation and
      regression and are directly linked to the activity of a single oncogene.

PMID- 21723513
TI  - Iterative image reconstruction techniques: Applications for cardiac CT.
AB  - BACKGROUND: Traditional limitations of cardiac CT are related to image noise,
      blooming artifacts from calcifications and stents, and radiation exposure. We
      evaluated whether these limitations can be ameliorated by the use of iterative
      reconstruction in image space (IRIS) instead of traditional filtered back
      projection (FBP) image reconstruction techniques. METHODS: We compared image
      reconstruction with the use of IRIS with traditional FBP for their effect on
      image quality, noise, volume of heavy coronary artery calcifications, and stents
      as a measure of "blooming" artifacts, and radiation dose at cardiac CT. The
      radiation dose comparison was performed as a matched pair analysis, whereas all
      other comparisons were performed within the same group of patients. RESULTS: The
      subjective image quality of IRIS reconstructions was rated higher than FBP
      reconstructions. Image noise was lower with IRIS than with FBP. The volume of
      stents and heavy coronary artery calcifications measured lower in IRIS
      reconstructed series compared with FBP. Similar levels of image noise were
      achieved with 80/100 kVp of tube voltage with IRIS compared with 120 kVp and FBP,
      resulting in a 62% reduction in effective dose. CONCLUSION: Our preliminary
      experiences suggest that IRIS incrementally improves the CT evaluation of
      coronary arteries, especially in challenging scenarios. Substantial radiation
      reduction seems feasible without associated increases in image noise.

PMID- 21723512
TI  - SCCT guidelines on radiation dose and dose-optimization strategies in
      cardiovascular CT.
AB  - Over the last few years, computed tomography (CT) has developed into a standard
      clinical test for a variety of cardiovascular conditions. The emergence of
      cardiovascular CT during a period of dramatic increase in radiation exposure to
      the population from medical procedures and heightened concern about the
      subsequent potential cancer risk has led to intense scrutiny of the radiation
      burden of this new technique. This has hastened the development and
      implementation of dose reduction tools and prompted closer monitoring of patient
      dose. In an effort to aid the cardiovascular CT community in incorporating
      patient-centered radiation dose optimization and monitoring strategies into
      standard practice, the Society of Cardiovascular Computed Tomography has produced
      a guideline document to review available data and provide recommendations
      regarding interpretation of radiation dose indices and predictors of risk,
      appropriate use of scanner acquisition modes and settings, development of
      algorithms for dose optimization, and establishment of procedures for dose
      monitoring.

PMID- 21723514
TI  - Relationship between chest lateral width, tube current, image noise, and
      radiation exposure associated with coronary artery calcium scanning on 320
      detector row CT.
AB  - BACKGROUND: The relationship between chest lateral width, tube current, image
      noise, and radiation exposure on 320-detector row CT has not been reported.
      OBJECTIVE: We investigated the relationships between chest lateral width,
      estimated radiation exposure (DLPe), and image noise in 300 patients undergoing
      clinical coronary calcium scanning. METHODS: Patients undergoing coronary calcium
      scanning with 320-detector row CT (prospective, volumetric mode, 120 kV of tube
      voltage, 100-550 mA of tube current, 0.5-mm detector width) were grouped by chest
      lateral width (small, medium, and large) from anteroposterior topograms and 100
      consecutive patients were selected from each group (n = 300). Tube current, DLPe,
      and noise were compared among groups with Kruskal-Wallis or one-way ANOVA.
      Phantom experiments were performed to evaluate the accuracy of calcium
      quantification as a function of size and tube current. RESULTS: Median tube
      current in small, medium, and large patients was 130, 200, and 250 mA,
      respectively (P < 0.0001). Despite the use of higher tube current settings, noise
      levels also increased with size (20.2 +/- 4.5 HU, 22.0 +/- 3.9 HU, and 25.1 +/-
      4.9 HU, respectively; global P < 0.001). DLPe was significantly higher with
      increasing size (54, 83, and 104 mGy . cm, respectively; P < 0.0001). Phantom
      experiments showed that 50-100 mA, 150-200 mA, and approximately 300 mA in small,
      medium, and large phantoms were associated with stable estimate of calcium.
      CONCLUSIONS: Increasing chest lateral width is associated with increasing
      radiation exposure and image noise. The use of 50-100 mA in small and 150-200 mA
      in medium patients is associated with acceptable noise and stable estimate of
      coronary artery calcium. In large patients, precise identification of individual
      calcified lesions remains difficult despite increasing tube current and radiation
      exposure.

PMID- 21723515
TI  - Direct chest area measurement: A potential anthropometric replacement for BMI to
      inform cardiac CT dose parameters?
AB  - BACKGROUND: Significant dose reductions for coronary CT angiography (CTA) can be
      achieved with reduced tube potential (kV); however, the potential effect on image
      quality is unknown. OBJECTIVE: We sought to evaluate anthropometric measures
      (chest area, chest circumference, and chest attenuation) as potentially better
      predictors of the appropriate tube potential versus body mass index (BMI).
      METHODS: Consecutive patients (n = 183) who underwent routine coronary CTA (with
      standard department protocols, whereby tube potential was selected according to
      BMI) between April 2010 and October 2010 were included. All anthropometric
      measures were obtained by tracing a region of interest encompassing an entire
      axial full field-of-view image at the mid left atrial level. Linear regression
      was used to stratify patients into 4 chest area classes (very small to large).
      Patients were also stratified by standard BMI classes (underweight to obese).
      Qualitative and quantitative image quality parameters were compared between
      concordant and discordant chest area and BMI classes. RESULTS: A strong
      correlation was observed between patients' BMI and chest area (r = 0.84; P <
      0.001) and between BMI and chest circumference (r = 0.82, P < 0.001). Concordance
      between chest area class and BMI class was found in 61%, whereas 17.6% of
      patients were "potentially underdosed" (chest area class > BMI class) and 21.4%
      were "potentially overdosed" (chest area class < BMI class). Signal and contrast
      of the proximal coronaries and left ventricle were significantly different
      between the groups. CONCLUSION: Patients' chest area and BMI classes were
      frequently discordant, potentially leading to overdosing or underdosing when
      using BMI to select tube potential.

PMID- 21723516
TI  - Detection of myocardial perfusion abnormalities using ultra-low radiation dose
      regadenoson stress multidetector computed tomography.
AB  - BACKGROUND: The ability of multidetector computed tomography (MDCT) to detect
      stress-induced myocardial perfusion abnormalities is of great clinical interest
      as a potential tool for the combined evaluation of coronary stenosis and its
      significance. However, stress testing requires repeated scanning that is
      associated with additional radiation exposure and iodine contrast. OBJECTIVE: Our
      goal was to determine the effects of reduced tube voltage and contrast dose on
      the ability to detect perfusion abnormalities. METHODS: We studied 40 patients
      referred for coronary CT angiography (CTA) who agreed to undergo additional
      imaging after administration of an A(2A)-agonist (regadenoson 0.4 mg). Images
      were acquired at rest and during hyperemia with prospective gating with 120 kV
      tube voltage with 80-90 mL of contrast in 20 patients (group 1) and 100 kV with
      55-70 mL of contrast in the remaining 20 patients (group 2). Custom 3D analysis
      software was used to define 3D myocardial segments and measure x-ray attenuation
      in each segment. In each group of patients, myocardial attenuation was averaged
      for segments supplied by coronary arteries with stenosis causing >50% luminal
      narrowing on coronary CTA and separately for segments supplied by arteries
      without significant stenosis. RESULTS: Coronary CTA detected stenosis >50% in 23
      of 120 coronary arteries in 16 of 40 patients. In all patients combined,
      myocardial attenuation increased from 86 +/- 9 at rest to 110 +/- 17 HU with
      stress, reflecting an increase in tissue blood flow, despite the decrease in left
      ventricular cavity attenuation (347 +/- 72 to 281 +/- 55 HU), reflecting an
      increase in cardiac output. Importantly, in both groups, myocardial attenuation
      was equally reduced in segments supplied by diseased arteries (group 1: 119 +/-
      19 vs 103 +/- 14 HU, P < 0.05; group 2: 108 +/- 20 vs 97 +/- 16 HU, P < 0.05),
      despite the 74% reduction in radiation (from 7.4 +/- 2.8 to 1.9 +/- 0.45 mSv) and
      the 28% reduction in contrast dose (from 84 +/- 7 to 60 +/-7 mL) (both P < 0.05).
      CONCLUSIONS: Regadenoson stress MDCT imaging can detect hypoperfused myocardium
      even when imaging settings are optimized to provide a significant reduction in
      radiation and contrast doses.

PMID- 21723517
TI  - The effect of heart rhythm on patient radiation dose with dual-source cardiac
      computed tomography.
AB  - BACKGROUND: To lower the radiation exposure associated with cardiac CT, it is
      essential to identify all factors that influence radiation dose. OBJECTIVES: We
      explored the effect of heart rhythm during scan acquisition on radiation dose
      with a 64-slice dual-source cardiac CT. METHODS: Patient and scan data were
      collected prospectively in 302 consecutive patients referred for a clinical dual
      source cardiac CT. Electrocardiograms recorded during acquisition were
      interpreted by a cardiologist and categorized as (1) normal sinus rhythm (NSR),
      (2) premature atrial contraction (PAC) or premature ventricular contraction
      (PVC), or (3) atrial fibrillation or flutter. RESULTS: Of the 302 patients, 227
      (75.2%) were in NSR and had no ectopy, 55 (18.2%) had PAC/PVC, and 20 (6.6%) had
      atrial fibrillation or flutter during the scan. Patients with irregular rhythm
      (PAC/PVC and atrial fibrillation or flutter) were older than patients with
      regular rhythm (61.0 vs 54.8 years; P = 0.006). Patients with NSR had the lowest
      estimated radiation dose, followed by PAC/PVC and atrial fibrillation/flutter
      (9.4, 14.5, 20.9 mSv; P < 0.001). The difference remained significant after
      adjustments for differences in examination type, tube current and voltage, scan
      length, pitch, and use of tube current modulation (9.8, 14.1, 17.9 mSv; P <
      0.001). No significant association was observed between heart rhythm and
      subjective image quality although scans with regular rhythm and no ectopy had
      higher signal-to-noise and contrast-to-noise ratios (P < 0.01). CONCLUSION:
      Compared to patients with NSR, patients with atrial fibrillation/flutter had the
      highest radiation exposure, followed by those with PAC/PVC. Even after adjustment
      for factors associated with radiation exposure, a significant difference in
      radiation dose persisted. These findings can be used to identify patients who are
      more likely to receive higher radiation dose when undergoing cardiac CT and to
      develop future more-efficient scanner algorithms for use in patients with
      arrhythmias.

PMID- 21723518
TI  - Radiation dose reduction with increasing utilization of prospective gating in 64
      multidetector cardiac computed tomography angiography.
AB  - BACKGROUND: Medical radiation exposure is a major concern, and several methods
      have been proposed to reduce radiation doses in multidetector cardiac computed
      tomography (CT). OBJECTIVE: The purpose of this study was to review radiation
      doses of clinical cardiac CT performed at our center and to evaluate the effect
      of radiation dose reduction strategies on the median dose delivered to patients
      over time. METHODS: This study included 623 consecutive clinical patients (male,
      58%) who were referred for imaging. The effective dose (mSv) was derived from the
      product of the dose-length-product (DLP) and a conversion coefficient for the
      chest (0.014). RESULTS: The median radiation dose of all patients was 3.0 mSv
      (interquartile range [IQR], 1.9-8.1 mSv). A significant difference was observed
      in radiation dose between the prospective (n = 384) and retrospective (n = 239)
      gating groups (2.0 vs 9.6 mSv; P < 0.0001). Compared with patients with coronary
      artery bypass grafting (CABG; n = 52), patients without CABG had significantly
      lower median radiation dose (prospective gating: 2.0 vs 3.4 mSv, P < 0.0001;
      retrospective gating: 9.3 vs 10.3 mSv, P < 0.0001). In patients with CABG, a
      significant difference was observed in radiation dose between prospective and
      retrospective gating (3.4 vs 10.3; P < 0.0001). The median radiation doses per
      month at our center decreased from 6.2 to 2.1 mSv over time with increasing use
      of prospective gating (<=91%). CONCLUSION: Radiation reduction techniques have
      led to progressive decreases in radiation exposure over time, primarily because
      of prospective gating.

PMID- 21723519
TI  - Cardiac CT: benefits outweigh the risks.

PMID- 21723520
TI  - WHO World Report on Disability: a review.
AB  - The World Health Organization in collaboration with the World Bank developed the
      World Report on Disability to inform governments of countries about the
      importance of disability, analyze scientific information, and provide
      recommendations for action at the national and international levels. The report
      is remarkably readable, comprehensive, and concise. There are recurrent themes of
      the connection between disability and poverty, and within disability groups, the
      relatively greater vulnerability of women, children, and persons with mental
      health disabilities. Chapter content includes an overview of disability, global
      view addressing measurement and prevalence, general health care, rehabilitation,
      assistance and supports, enabling environments, education, work and employment,
      and recommendations for moving forward. The report successfully illustrates a
      great need for improved data, policies, and programs, while describing promising
      practices that can inform policy makers in addressing these needs. This report is
      highly recommended reading for anyone interested in a global view on disability
      and should be required reading for any students in disability and public health.

PMID- 21723521
TI  - Parenting aggravation and autism spectrum disorders: 2007 National Survey of
      Children's Health.
AB  - BACKGROUND: Studies suggest autism spectrum disorders (ASDs) are associated with
      high parenting stress and aggravation. Research on specific risk factors is
      needed. OBJECTIVE/HYPOTHESES: To assess aggravation level among parents of
      children with and without ASDs. METHODS: The sample of 73,030 children aged 4 to
      17 years in the 2007 National Survey of Children's Health and their parent
      respondents were divided into mutually exclusive groups based on child ASD status
      and other special health care needs. Adjusted prevalence ratios (aPR) for
      associations between a high Aggravation in Parenting scale score and various risk
      factors were computed from multivariable models. RESULTS: High-aggravation
      percentages were comparable for parents of children with a current ASD (36.6%),
      ASD reported previously but not currently (35.2%), and another (non-ASD)
      developmental problem (31.2%) but were significantly lower for parents of
      children with other special health care needs (6.5%) and no special health care
      needs (5.1%). Within the current-ASD group, high aggravation was associated with
      young child age (aPR = 1.8 [1.2-2.6]), lack of health insurance (aPR = 1.5 [1.0
      2.4]), lack of a medical home (aPR = 2.2 [1.4-3.5]), recent child mental health
      treatment (aPR = 2.1 [1.5-3.0]), lack of parenting emotional support (aPR = 1.5
      [1.1-2.1]), and ASD severity (aPR = 1.4 [1.0-1.6]). Some of these same factors
      were associated with aggravation in the non-ASD groups. However, the medical home
      finding was specific to the ASD groups. CONCLUSIONS: Parenting a child with ASD
      is associated with high aggravation; however, there is variability within health
      care and social support subgroups. Strategies to strengthen medical home
      components for children with ASDs should be considered.

PMID- 21723522
TI  - Feasibility of expanding NEISS-AIP to create a scientific database on violence
      and disability.
AB  - BACKGROUND: This study identifies a feasible approach to an evidence-based source
      of information about violence and disability. OBJECTIVE: The purpose was to
      determine the feasibility of using the National Electronic Injury Surveillance
      System-All Injury Program (NEISS-AIP) to collect data about violence and
      disability, by identifying intentional injuries of patients with disabilities in
      NEISS hospital emergency departments. METHODS: Protocols were developed for
      collecting information about essential variables on violence and disability,
      training of NEISS hospital coordinators and emergency department staff, and
      evaluating the procedures by NEISS hospital coordinators. Ten NEISS hospital
      emergency departments were selected at random from the total of 64 NEISS
      hospitals. The protocols were applied in a data collection effort of 6 months.
      The data were weighted and sent to the researcher for further examination and
      analysis. Feasibility was determined by the evidence provided by the data
      collection and analysis and examination of the program evaluation questionnaire
      completed by each of the NEISS hospital coordinators. RESULTS: Inspection of the
      data and the evaluations completed by the NEISS hospital coordinators supported
      the feasibility of the study with a recommendation for more intense training to
      better categorize the type of disabilities in the future study population.
      CONCLUSIONS: The utilization of NEISS-AIP for the purpose of developing a more
      scientific database on violence and disability with capability of providing
      national estimates is feasible. Based on this feasibility study, the researcher
      will move to the next stage of an expanded study.

PMID- 21723523
TI  - Risky business: the effects of an individualized health information intervention
      on health risk perceptions and leisure time physical activity among people with
      spinal cord injury.
AB  - BACKGROUND: Individuals with spinal cord injury (SCI) are at an increased risk
      for inactivity-related diseases such as heart disease, type 2 diabetes, and
      obesity. According to protection motivation theory, perceptions of disease risk
      predict motivation to engage in health-protective behaviors such as leisure time
      physical activity (LTPA). OBJECTIVE: The purposes of this study were to (1)
      examine changes in perceived risk for disease following an individualized health
      information intervention and (2) examine changes in perceived risk for disease as
      a predictor of changes in LTPA. METHODS: Perceived risk for disease and LTPA were
      measured at baseline among 62 people with SCI. Objective disease risk information
      (e.g., waist circumference, BMI, blood glucose) was collected and individual risk
      information was mailed to each participant. Perceived risk for disease and LTPA
      were remeasured 1 and 2 weeks following receipt of individualized information,
      respectively. RESULTS: Changes in perceived risk of heart disease and obesity
      were dependent on objective risk status. There were no significant changes in
      perceived risk of diabetes. Changes in perceived risk of heart disease negatively
      predicted, while changes in perceived risk of diabetes positively predicted,
      changes in LTPA. Changes in obesity did not significantly predict changes in
      LTPA. CONCLUSIONS: Among people with SCI, individual health-risk information can
      change perceptions of disease risk. Increased perceived risk of diabetes may
      motivate LTPA, while increased perceived risk of heart disease may encourage
      avoidance behavior regarding LTPA.

PMID- 21723524
TI  - Perceived stigma, strain, and mental health among caregivers of veterans with
      traumatic brain injury.
AB  - BACKGROUND: Family caregivers of individuals with stigmatized conditions can
      experience stigma-by-association and discrimination. Moderate-to-severe traumatic
      brain injury (TBI) may elicit a stigma response if there are visible physical or
      neurobehavioral effects of the injury. Stigma is a considerable source of stress
      and may contribute to caregiver strain and stress-related mental health outcomes.
      We measured the frequency of perceived stigma and discrimination among caregivers
      of veterans with TBI and examined whether perceived stigma and discrimination are
      associated with caregiver strain, social isolation, depression, and anxiety.
      METHODS: Seventy caregivers of veterans with TBI completed a mailed survey that
      assessed perceptions of discrimination toward themselves or their care recipient,
      stigma associated with caregiving, and whether they felt the need to cover up or
      provide an explanation for their care recipient's injury. Caregiver strain,
      social isolation, depression, and anxiety were also assessed via the
      questionnaire. Multivariate linear regression was used to test the associations
      between stigma and discrimination measures and outcomes, controlling for
      potential confounders and other caregiver or care recipient characteristics.
      RESULTS: Both perceptions of caregiver discrimination and stigma associated with
      caregiving were significantly associated with caregiver strain, social isolation,
      depression, and anxiety. Perceived discrimination against the individual with TBI
      was associated with caregiver strain and social isolation. CONCLUSIONS: Our
      findings suggest that perceived discrimination and stigma experienced by
      caregivers of individuals with TBI are stressors that may lead to poor caregiver
      mental health outcomes. In order to promote both caregiver and care recipient
      health, we suggest that mental health support services consider these important
      stressors.

PMID- 21723525
TI  - Health and educational status of children raised by a caregiver with a
      disability.
AB  - BACKGROUND: Research on children raised by adults with disability is limited. Our
      goal was to provide a profile of the health and educational status of children
      raised by a caregiver with disability. METHODS: In 2007-2008, 4571 adults
      completed the North Carolina Behavior Risk Factor Surveillance System (BRFSS) and
      Child Health Assessment Monitoring Program (CHAMP) surveys. Analyses using
      weighted data provided population-based health/educational status comparisons of
      children (0 to 17 years old) raised by caregivers with and without disability.
      RESULTS: Twenty-three percent of caregivers reported disability. Rates of
      insurance coverage and preventive care did not differ by caregiver disability
      status, although children of caregivers with disability were more likely to have
      publicly funded insurance. The majority of children of caregivers with disability
      were in excellent/very good health (70%), healthy weight (58%), and making above
      average grades (74%). Nonetheless, children raised by caregivers with disability
      appear to be at disproportionately higher risk for overall poorer outcomes.
      Children raised by caregivers with disability were more likely to be in fair/poor
      health (adjusted odds ratio [aOR] 2.2; 95% confidence interval [CI] 1.3 to 3.6),
      overweight/obese (aOR = 1.5, 95% CI 1.1-2.0), need medical/educational services
      (aOR = 2.0, 95% CI 1.5-2.6), have lower grades (aOR = 1.9, 95% CI 1.4-2.5), and
      higher rates of school absenteeism (aOR = 2.4, 95% CI 1.8-3.4), compared to
      children of caregivers without disability. CONCLUSION: Children raised by a
      caregiver with disability show good overall wellness; however, caregiver
      disability status was found to be associated with an increased risk for poor
      child health and educational outcomes. Future research is needed to clarify the
      causes of these disparities and inform policies to alleviate them.

PMID- 21723526
TI  - Perceptions of cardiovascular health in an underserved community of deaf adults
      using American Sign Language.
AB  - BACKGROUND: Cardiovascular disease leads in overall mortality and morbidity in
      the United States. Cardiovascular disparities remain high among minority and
      underserved groups. Deaf American Sign Language (ASL) users are an underserved
      and understudied group that receives little attention from researchers due to
      language and communication barriers. A recent ASL survey in Rochester, NY,
      indicated greater cardiovascular risk among Deaf participants. The study
      objective was to investigate risk perceptions of cardiovascular disease among
      Deaf ASL users, linking perceptions to features of Deaf culture and
      communication. This information will be used to inform future strategies to
      promote cardiovascular health among Deaf adults. METHODS AND PARTICIPANTS: Four
      focus groups were conducted in Rochester, New York, with 22 Deaf participants in
      ASL. Videotaped sessions were translated and transcribed by a bilingual
      researcher. A team of investigators coded, analyzed, and identified key themes
      from the data. MAIN RESULTS: Themes centered on five major domains: knowledge,
      barriers, facilitators, practices, and dissemination. The majority of themes
      focused on barriers and knowledge. Barriers included lack of health care
      information access due to language and communication challenges, financial
      constraints, and stress. Inconsistent knowledge emerged from many key areas of
      cardiovascular health. CONCLUSIONS: The study outlines key themes for improving
      cardiovascular health knowledge and perceptions among Deaf ASL users. Findings
      suggest the importance of providing health educational programs and information
      in ASL to maximize understanding and minimize misconceptions. When caring for
      Deaf ASL users, providers should take extra effort to ask about cardiovascular
      risk factors and confirm patients' understanding of these factors.

PMID- 21723527
TI  - A reply to: the myth and reality of disability prevalence: measuring disability
      for research and service.

PMID- 21723529
TI  - Comparison of myocardial ischemia during intense mental stress using flight
      simulation in airline pilots with coronary artery disease to that produced with
      conventional mental and treadmill exercise stress testing.
AB  - Mental stress increases cardiovascular morbidity and mortality. Although
      laboratory mental stress often causes less myocardial ischemia than exercise
      stress (ES), it is unclear whether mental stress is intrinsically different or
      differences are due to less hemodynamic stress with mental stress. We sought to
      evaluate the hemodynamic and ischemic response to intense realistic mental stress
      created by modern flight simulators and compare this response to that of exercise
      treadmill testing and conventional laboratory mental stress (CMS) testing in
      pilots with coronary disease. Sixteen airline pilots with angiographically
      documented coronary disease and documented myocardial ischemia during ES were
      studied using maximal treadmill ES, CMS, and aviation mental stress (AMS)
      testing. AMS testing was done in a sophisticated simulator using multiple system
      failures as stressors. Treadmill ES testing resulted in the highest heart rate,
      but AMS caused a higher blood pressure response than CMS. Maximal rate-pressure
      product was not significantly different between ES and AMS (25,646 vs 23,347, p =
      0.08), although these were higher than CMS (16,336, p <0.0001). Despite similar
      hemodynamic stress induced by ES and AMS, AMS resulted in significantly less ST
      segment depression and nuclear ischemia than ES. Differences in induction of
      ischemia by mental stress compared to ES do not appear to be due to the creation
      of less hemodynamic stress. In conclusion, even with equivalent hemodynamic
      stress, intense realistic mental stress induced by flight simulators results in
      significantly less myocardial ischemia than ES as measured by ST-segment
      depression and nuclear ischemia.

PMID- 21723530
TI  - Usefulness of left ventricular diastolic dysfunction assessed by pulsed tissue
      Doppler imaging as a predictor of atrial fibrillation recurrence after successful
      electrical cardioversion.
AB  - The impact of left ventricular (LV) diastolic dysfunction on risk of atrial
      fibrillation (AF) recurrence is still unknown. The aim of this study was to
      assess the role of LV diastolic dysfunction in predicting AF recurrence after
      successful electrical cardioversion in patients with nonvalvular AF. In 51
      patients with a first episode of nonvalvular AF undergoing successful electrical
      cardioversion, tissue Doppler echocardiography was performed to measure peak
      early diastolic mitral annulus velocity (E(m)) and the ratio of mitral inflow to
      mitral annulus velocity at end-diastole (E/E(m)). Clinical end points were
      recurrent persistent AF at 2-week follow-up (early AF recurrence [ERAF]) and at 1
      year follow-up (including ERAF and late AF recurrence). Seventeen patients showed
      evidence of ERAF, whereas late AF recurrence occurred in another 5 patients. In
      time-independent analysis E/E(m) (odds ratio [OR] 1.746, p = 0.0084) and indexed
      LV end-systolic volume (OR 1.083, p = 0.040) were independent predictors of ERAF.
      Based on a logistic model risk of ERAF was 25% for an E/E(m) of 5.6 but increased
      to 50% for an E/E(m) of 8.1 and to 75% for an E/E(m) of 10.5. In time-dependent
      analysis E/E(m) emerged as the only predictor of ERAF (OR 1.757, p = 0.0078).
      E/E(m) also independently predicted risk of recurrence at 1 year in time
      independent (OR 1.757, p = 0.0078) and time-dependent (OR 1.319, p = 0.0003)
      analyses. In conclusion LV diastolic dysfunction independently predicts AF
      recurrence in patients with nonvalvular AF undergoing successful electrical
      cardioversion.

PMID- 21723531
TI  - Examination of isolated ventricular noncompaction (hypertrabeculation) as a
      distinct entity in adults.
AB  - Three patients (2 women) 36, 45, and 49 years of age underwent cardiac
      transplantation for what was diagnosed clinically as nonischemic dilated
      cardiomyopathy. Examination of the transthoracic echocardiogram and explanted
      heart in each disclosed marked hypertrabeculation involving the free wall of the
      very dilated left ventricle, a finding consistent with what has been termed
      "isolated ventricular noncompaction" (IVNC). Although these 3 cases anatomically
      fulfilled the echocardiographic definition of IVNC, review of previous
      publications containing gross photographs of the heart suggests that IVNC is
      overdiagnosed at least morphologically.

PMID- 21723532
TI  - Intraocular oxygen distribution in advanced proliferative diabetic retinopathy.
AB  - PURPOSE: To determine the preretinal distribution of oxygen in advanced
      proliferative diabetic retinopathy, and to investigate the relationship between
      intraocular oxygen tensions and vitreous cytokine concentrations. DESIGN:
      Comparative cross-sectional study. METHODS: Oxygen levels were measured at sites
      in the vitreous and at the inner retinal surface using an optical oxygen sensor
      in 14 control subjects and in 14 subjects with advanced proliferative diabetic
      retinopathy who had developed tractional retinal detachments despite previous
      panretinal photocoagulation. The vitreous and plasma concentrations of 42
      cytokines were measured using multiplex cytokine arrays and their correlation
      with intraocular oxygen tension was investigated. RESULTS: The mean oxygen
      tension in the mid-vitreous in diabetic retinopathy was 46% lower than that in
      control subjects (P = .017). However, the mean preretinal oxygen tension at the
      posterior pole in diabetic retinopathy was 37% higher than in controls (P =
      .039). We measured significant alterations in the vitreous concentrations of 9
      cytokines-eotaxin, Flt-3 ligand, growth-related oncogene (GRO), interleukin (IL)
      6, IL-8, IL-9, IFN-inducible protein-10 (IP-10), macrophage-derived cytokine
      (MDC), and vascular endothelial growth factor (VEGF)-in advanced proliferative
      diabetic retinopathy, and found that oxygen tension at the posterior pole was
      directly correlated with vitreous VEGF concentration. CONCLUSION: We identified
      significant intraocular oxygen gradients in proliferative diabetic retinopathy.
      Our findings are consistent with the hypothesis that VEGF induces the development
      of neovascular complexes in the posterior retina that are richly perfused but
      nonetheless fail to redress hypoxia in the mid-vitreous. Upregulation of vitreous
      VEGF may be a consequence of retinal hypoxia at unidentified sites or of chronic
      inflammatory processes in advanced proliferative diabetic retinopathy.

PMID- 21723533
TI  - Impact of image analysis methodology on diagnostic and surgical classification of
      patients with thoracic aortic aneurysms.
AB  - BACKGROUND: For patients with thoracic aortic aneurysms (TAA), aortic size on
      imaging is widely used to guide clinical decision making. This study examined the
      impact of methodological variance on aortic quantification. METHODS: We studied
      enrollees in the National Registry of Genetically Triggered Thoracic Aortic
      Aneurysms and Cardiovascular Conditions. Aortic size on computed tomography was
      quantified by 2 linear methods; cross-sectional dimensions in axial (AX) and
      double oblique (DO) plane. Calculated area was compared to planimetry.
      Established cutoffs (area/height>10 cm2/m, diameter>=5 cm) for prophylactic TAA
      repair were used to compare surgical eligibility by each method. RESULTS: Fifty
      subjects were studied. Aortic size differed between AX and DO at all locations
      (p<=0.001), with magnitude greatest at the sinotubular junction (4.8+/-1.1 vs
      4.0+/-1.0 cm, p<0.001). The difference between AX and DO correlated with aortic
      angular displacement (r=0.37, p<0.01), which was threefold larger at the
      sinotubular junction (37+/-12 degrees) than the ascending aorta (12+/-5 degrees;
      p<0.001). At all locations, aortic area calculated using DO yielded smaller
      differences with planimetry than AX (p<0.05). DO and planimetry yielded equal
      prevalence (24%) of subjects eligible for prophylactic TAA repair based on area
      height cutoff, whereas AX prevalence was higher (44%; p=0.006). Using a linear
      cutoff, AX yielded over a twofold greater prevalence of surgically eligible
      subjects (56%) than did DO (24%; p<0.001). CONCLUSIONS: Established linear
      methods for aortic measurement yield different results that impact surgical
      eligibility. DO yielded improved agreement with planimetry and differed with AX
      in proportion to aortic geometric obliquity. Findings support DO measurements for
      imaging evaluation of subjects with TAA.

PMID- 21723534
TI  - The role of treatment expectancy in youth receiving exposure-based CBT for
      obsessive compulsive disorder.
AB  - The purpose of this investigation was to examine correlates of parent, child, and
      therapist treatment expectations and their role in the exposure-based treatment
      of childhood obsessive compulsive disorder (OCD). Treatment expectations were
      assessed among 49 youth with primary OCD, their parents, and therapists as part
      of the baseline evaluation and post-treatment clinical outcomes were determined
      by blind evaluators. Baseline depressive symptoms, child/parent-rated functional
      impairment, externalizing behavior problems, number of comorbid psychiatric
      disorders, and a lower perception of control were associated with lower pre
      treatment expectations. Parent expectation was associated with parental OCD
      symptoms, child depressive symptoms and child-reported impairment. Therapist
      expectations inversely correlated with child depressive symptoms, externalizing
      problems, and child-rated impairment. Pre-treatment OCD severity and prior
      treatment history were not linked to expectancy. Finally, higher treatment
      expectations were linked to better treatment response, lower attrition, better
      homework compliance, and reduced impairment.

PMID- 21723535
TI  - Brain energy depletion in a rodent model of diffuse traumatic brain injury is not
      prevented with administration of sodium lactate.
AB  - Lactate has been identified as an alternative fuel for the brain in situations of
      increased energy demand, as following a traumatic brain injury (TBI). This study
      investigates the effect of treatment with sodium lactate (NaLac) on the changes
      in brain energy state induced by a severe diffuse TBI. Rats were assigned to one
      of the eight groups (n=10 per group): 1-sham, normal saline; 2-TBI, normal
      saline; 3-TBI, hypertonic saline; 4-TBI, 100mM NaLac, 5-TBI, 500 mM NaLac; 6-TBI,
      1280 mM NaLac; 7-TBI, 2000 mM NaLac and 8-TBI-500 mM NaLac+magnesium sulfate.
      Cerebrums were removed 6h after trauma. Metabolites representative of the energy
      state (ATP, ATP-catabolites), N-acetylaspartate (NAA), antioxidant defenses
      (ascorbic acid, glutathione), markers of oxidative stress (malondialdehyde, ADP
      ribose) and nicotinic coenzymes (NAD(+)) were measured by HPLC. TBI induced a
      marked decrease in the cerebral levels of ATP, NAA, ascorbic acid, glutathione
      and NAD(+) and a significant rise in the content of ATP-catabolites,
      malondialdehyde and ADP-ribose. These alterations were not ameliorated with NaLac
      infusion. We observed a significant reduction in cerebral NAD(+), an essential co
      enzyme for mitochondrial lactate-dehydrogenase that converts lactate into
      pyruvate and thus replenishes the tricarboxylic acid cycle. These results suggest
      that the metabolic pathway necessary to consume lactate may be compromised
      following a severe diffuse TBI in rats.

PMID- 21723536
TI  - The emergence of the "motoneuron concept": from the early 19th C to the beginning
      of the 20th C.
AB  - This article addresses the emergence of the "motoneuron concept," i.e., the idea
      that this cell had properties of particular advantage for its control of muscle
      activation. The motor function of the ventral roots was established early in the
      19th C and the term "motor cell," (or "motor nerve cell") was introduced shortly
      thereafter by Albrecht von Kolliker and some other histologists. They knew that
      motor cells were among the neurons with the largest soma in vertebrates and for
      this reason they were, and remained for many decades, the best and most studied
      neuronal model. The work of clinicians like Guillaume Duchenne de Boulogne and
      Jean-Martin Charcot on motor degenerative syndromes began before a clear
      description of motor cells was available, because it was initially more difficult
      to establish whether the deficits of paralysis and muscle weakness were due to
      neuronal or muscular lesions. Next, the pioneering physiologist, Charles
      Sherrington, who was influenced greatly by the anatomical contributions and
      speculations of Santiago Ramon y Cajal, used the term, "motor neuron," rather
      than motor cell for the neuron that he considered was functionally "the final
      common path" for providing command signals to the musculature. In the early 20th
      C he proposed that activation of a motor neuron resulted from the sum of its
      various excitatory and inhibitory CNS inputs. The contraction of motor neuron to
      "motoneuron(e)" was put into common usage by John Fulton (among possibly others)
      in 1926. The motoneuron concept is still evolving with new discoveries on the
      horizon.

PMID- 21723537
TI  - Lactobacilli secreting a tumor antigen and IL15 activates neutrophils and
      dendritic cells and generates cytotoxic T lymphocytes against cancer cells.
AB  - Lactobacillus rhamnosus GG (LGG) has been used to successfully induce tumor
      regression in an orthotopic model of bladder cancer. Increased infiltration of
      neutrophils and macrophages into the tumor mass was observed after therapy. This
      study evaluates the potential of LGG to induce a directed anti-tumor response.
      Lactobacilli were modified to secrete the prostate specific antigen (PSA) or IL15
      and PSA (IL-15-PSA). Neutrophils and DC were exposed to LGG for 2 h as in
      clinical therapy for bladder cancer. Recombinant LGG activated neutrophils
      (elevated MHC class I expression) induced DC maturation (increased expression of
      CD86, CD80, CD40, MHC II and CD83), T cell proliferation and PSA specific
      cytotoxic T lymphocytes (CTL) activity. IL15 enhanced direct DC activation of
      CTL. Thus LGG secreting tumor antigens may activate antigen specific immune
      responses when instilled intravesically and IL15 could enhance this response.

PMID- 21723538
TI  - [New advances in the treatment of varicose veins: endovenous radiofrequency VNUS
      Closure(r)].
AB  - Lower limb varicose veins are often secondary to greater saphenous vein (GSV)
      insufficiency. Technological development has led to the appearance of new
      minimally invasive treatments, such as endovenous radiofrequency ablation (ERFA).
      This almost completely eliminates the disadvantages associated with conventional
      surgery (haematomas, scars, inguinal neovascularisation, and a prolonged time off
      work). Furthermore, it gives a better quality of life, less pain and inflammation
      than the endolaser. We review ERFA and present our results as a pioneering group
      in Spain. Between January 2006 and 2011 we have treated 153 limbs with a mean GSV
      diameter of 6.8 mm (range 4.5-19). Tumescent anaesthesia was exclusively used in
      71% of the procedures, and 98.5% without an inguinal surgical approach. Clinical
      and ultrasound follow-up with a prospective register was performed at 1 week, 3,
      6, 12 months, and then annually. RESULTS: The occlusion rate of the treated vein
      was 97%, and there was a reflux rate of 6.6%. Inguinal neovascularisation was
      present on 0.7%. There was no neuritis, skin burns or deep vein thrombosis.

PMID- 21723540
TI  - [Endovascular treatment of an ilio-iliac arteriovenous fistula after lumbar
      laminectomy].

PMID- 21723542
TI  - [Management of hepatic trauma: four years experience].
AB  - INTRODUCTION: The liver is the second most damaged organ in abdominal trauma. The
      purpose of this article is to present the experience of our regional reference
      hospital and summarise the management of these types of injury over the last four
      years. PATIENTS AND METHODS: An observational, descriptive and retrospective
      study was performed on patients with hepatic trauma admitted to our Department
      from January 2006 to March 2010. The clinical variables collected were: age, sex,
      aetiology, injury type, presence of haemodynamic stability and peritonism, type
      of treatment, and complications. RESULTS: The study included 17 patients, with a
      mean age of 25.3 years, and 12 of them were male. Ten patients received non
      surgical treatment. Of those who received surgical treatment, packing was
      performed on 3, with one of them requiring a hemi-hepatectomy in a second
      operation. There were complications in 4 patients, 2 surgical and 2 non-surgical.
      DISCUSSION AND CONCLUSIONS: The most important criterion for the choice of non
      surgical treatment is haemodynamic stability. The most recommended surgical
      technique for the rapid control of liver bleeding is compression packing,
      achieving stabilisation and to transfer the patient to a hospital with experience
      in hepatic surgery.

PMID- 21723541
TI  - [Changes in the diagnosis and therapeutic management of hepatic trauma. A
      retrospective study comparing 2 series of cases in different (1997-1984 vs. 2001
      2008)].
AB  - INTRODUCTION: We present a series of 146 cases of hepatic trauma (HT) treated in
      our hospital over a period of 8 yearsm (2001-2008), and comparing it with a
      previous series of 92 cases (1977-1984). MATERIAL AND METHOD: The mean age in the
      current series was 28.6 years and the majority were male. The closed traumas were
      mainly penetrating, with the most frequent cause being road traffic accidents.
      RESULTS: The American Association for the Surgery of Trauma (AAST) classification
      was used to evaluate the grade of the hepatic injury. Associated abdominal and
      /or extra-abdominal injuries were seen in 79.5% of the patients, with the most
      frequent being chest trauma, compared to bone fractures in the previous series.
      The most common associated intra-abdominal injury was the spleen in both series.
      The most used diagnostic technique in the current series was abdominal CT. Simple
      peritoneal puncture and lavage (PLP) were the most used examinations used in the
      previous series. Non-surgical treatment (NST) was given in 98 cases and the
      surgery was indicated in the remaining 48. In the previous series, 97.8% of
      patients were operated on. In the current series, on the 15 patients with severe
      liver injuries, 5 right hepatectomies, 2 segmentectomies and 6 packing
      compressions were performed, with the remaining two dying during surgery due to
      hepatic avulsion. The overall mortality was 3.4%, being 1% in the NST group and
      8.3% in the surgical patients. In the previous series, the overall mortality was
      29.3%. CONCLUSIONS: The key factor for using NST is to control haemodynamic
      stability, leaving surgical treatment for haemodynamically unstable patients.

PMID- 21723543
TI  - [Castleman's disease of the pelvis].

PMID- 21723544
TI  - [Benign non-parasitic hepatic cystic tumours].
AB  - Hepatic cystic tumours are a heterogeneous group of diseases with different
      aetiology and incidence, and with similar clinical signs and symptoms. They are
      classified as congenital, traumatic, parasitic, or neoplastic cysts. The
      congenital cystic tumours are the most prevalent, and include the simple cyst and
      polycystic hepatic disease. Other less common lesions are, hepatic cystadenoma,
      ciliated embryonic cyst, and a miscellaneous group. We have carried out a review
      of all benign non-parasitic hepatic cystic tumours, placing special emphasis on
      therapeutic strategies.

PMID- 21723546
TI  - [Treatment of a haemorrhagic pseudocyst of pancreas].

PMID- 21723547
TI  - [Compression therapy after varicose vein surgery. Can the classic elastic bandage
      be improved upon?].

PMID- 21723548
TI  - Infants' understanding of actions performed by mechanical devices.
AB  - Recent research suggests that 9-month-old infants tested in a modified version of
      the A-not-B search task covertly imitate actions performed by the experimenter.
      The current study examines whether infants also simulate actions performed by
      mechanical devices, and whether this varies with whether or not they have been
      familiarized with the devices and their function. In Experiment 1, infants
      observed hiding and retrieving actions performed by a pair of mechanical claws on
      the A-trials, and then searched for the hidden toy on the B-trial. In Experiment
      2, infants were first familiarized with the experimenter and the claws but not
      their function. In Experiment 3, infants were familiarized with the function of
      the claws. The results revealed that search errors were at chance levels in
      Experiments 1 and 2, but a significant proportion of the infants showed the A-not
      B error in Experiment 3. These results suggest that 9-month-old infants are less
      likely to simulate observed actions performed by mechanical devices than by human
      agents, unless they are familiarized with the function of the devices so that
      their actions are perceived as goal-directed.

PMID- 21723549
TI  - The role of beliefs in lexical alignment: evidence from dialogs with humans and
      computers.
AB  - Five experiments examined the extent to which speakers' alignment (i.e.,
      convergence) on words in dialog is mediated by beliefs about their interlocutor.
      To do this, we told participants that they were interacting with another person
      or a computer in a task in which they alternated between selecting pictures that
      matched their 'partner's' descriptions and naming pictures themselves (though in
      reality all responses were scripted). In both text- and speech-based dialog,
      participants tended to repeat their partner's choice of referring expression.
      However, they showed a stronger tendency to align with 'computer' than with
      'human' partners, and with computers that were presented as less capable than
      with computers that were presented as more capable. The tendency to align
      therefore appears to be mediated by beliefs, with the relevant beliefs relating
      to an interlocutor's perceived communicative capacity.

PMID- 21723550
TI  - Education and neuroscience: what kind of marriage?

PMID- 21723551
TI  - Captopril as a novel possible treatment for children with ADHD and elevated lead
      level, a hypothesis.

PMID- 21723552
TI  - A weighted multi-scale morphological gradient filter for rolling element bearing
      fault detection.
AB  - This paper presents a novel signal processing scheme, named the weighted multi
      scale morphological gradient filter (WMMG), for rolling element bearing fault
      detection. The WMMG can depress the noise at large scale and preserve the
      impulsive shape details at small scale. Both a simulated signal and vibration
      signals from a bearing test rig are employed to evaluate the performance of the
      proposed technique. The traditional envelope analysis and a multi-scale
      enveloping spectrogram algorithm combining continuous wavelet transform and
      envelope analysis (WT-EA) are also studied and compared with the presented WMMG.
      Experimental results have demonstrated the effectiveness of the WMMG to extract
      the impulsive components from the raw vibration signal with strong background
      noise. We also investigated the classification performance on identifying bearing
      faults based on the WMMG and statistical parameters with varied noise levels.
      Application results reveal that the WMMG achieves the same or better performance
      as EA and WT-EA. Meanwhile, the WMMG requires low computation cost and is very
      suitable for on-line condition monitoring of bearing operating states.

PMID- 21723553
TI  - The use of bone graft substitutes in large cancellous voids: any specific needs?
AB  - Bone graft is the second most common transplantation tissue, with blood being by
      far the commonest. Autograft is considered ideal for grafting procedures,
      providing osteoinductive growth factors, osteogenic cells and an osteoconductive
      scaffold. Limitations, however, exist regarding donor site morbidity and graft
      availability. Allograft on the other hand poses the risk of disease transmission.
      Synthetic graft substitutes lack osteoinductive or osteogenic properties.
      Composite grafts combine scaffolding properties with biological elements to
      stimulate cell proliferation and differentiation and eventually osteogenesis. We
      present here an overview of bone graft substitutes available for clinical
      application in large cancellous voids.

PMID- 21723554
TI  - Casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro improves central blood
      pressure and arterial stiffness in hypertensive subjects: a randomized, double
      blind, placebo-controlled trial.
AB  - OBJECTIVE: This trial evaluated the effects of casein hydrolysate containing milk
      derived peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), on central blood
      pressure and arterial stiffness. METHODS: A randomized, double-blind, placebo
      controlled trial was conducted in 70 Japanese subjects aged 50-69 years with
      untreated stage-I hypertension. They were randomly assigned to two groups, which
      received either placebo tablets or active tablets containing 3.4 mg of VPP and
      IPP. At the beginning and end of the 8-week intervention, hemodynamic parameters,
      including central blood pressure and brachial-ankle pulse wave velocity (baPWV),
      a marker of arterial stiffness, were measured. RESULTS: A significant difference
      in changes in central systolic blood pressure between the groups was observed
      (active: -11.0+/-11.0 vs placebo: -4.5+/-9.6 mmHg, P<0.01). In the active group,
      reductions in baPWV (-73.9+/-130.0 vs -8.4+/-137.1 cm/s, P<0.05), brachial SBP (
      10.5+/-11.5 vs -3.9+/-9.6 mmHg, P<0.05), and radial mean blood pressure (-7.3+/
      8.9 vs -2.0+/-7.4 mmHg, P<0.01) were significantly greater as compared with the
      placebo group. CONCLUSION: Casein hydrolysate containing VPP and IPP improves
      central SBP and baPWV in hypertensive subjects, which suggests VPP and IPP might
      have beneficial effects on arterial properties.

PMID- 21723555
TI  - Serum paraoxonase activity and oxidative stress in patients with adult nephrotic
      syndrome.
AB  - OBJECTIVE: It has been shown that low paraoxonase-1 (PON1) activity is associated
      with a risk of an early development of atherosclerosis. In the present study, we
      investigated serum paraoxonase, and arylesterase activities and oxidative stress
      in patients with adult nephrotic syndrome (NS). In addition, we examined the
      relationship between these measurements and atherosclerosis. METHODS: Twenty-one
      patients with NS and 21 healthy controls were enrolled in the study. Serum basal
      and salt-stimulated paraoxonase activities, arylesterase activity, lipid
      hydroperoxide (LOOH) and total thiol (SH) levels were measured. RESULTS: Serum
      basal and salt-stimulated paraoxonase activities, arylesterase activity and total
      SH levels were significantly lower in patients with NS than in controls (p<0.05,
      p<0.05, p<0.01 and p<0.05, respectively), whereas LOOH levels were significantly
      higher (p<0.05). Serum LOOH levels were significantly correlated with total-SH
      levels in patients with NS (r=-0.467; p<0.01). Moreover, proteinuria levels were
      significantly correlated with serum LOOH levels (r=0.397; p<0.01), whereas no
      correlation was found among serum paraoxonase activity, arylesterase activity and
      total-SH levels in NS patients (p>0.05). CONCLUSIONS: We concluded that oxidative
      stress is increased, while serum PON1 activity is decreased in patients with
      adult NS. In addition, these results indicate that lower PON1 activity is
      associated with an oxidant-antioxidant imbalance that may contribute to
      atherosclerosis in adult patients with NS.

PMID- 21723556
TI  - Computed high concentrations of low-density lipoprotein correlate with plaque
      locations in human coronary arteries.
AB  - Subendothelial accumulation of low-density lipoprotein (LDL) in arterial walls is
      an initiator of atherosclerotic plaque formation. We report here on the
      correlation between healthy state subendothelial LDL concentration distribution
      and sites of subsequent plaque formation in coronary arteries of patients with
      coronary artery disease (CAD). We acquired left (LCA) and right coronary artery
      (RCA) and atherosclerotic plaque geometries of 60 patients with CAD using dual
      source computed tomography angiography. After virtually removing all plaques to
      obtain an approximation of the arteries' healthy state, we calculated LDL
      concentration in the artery walls as a function of local lumen-side shear stress.
      We found that maximum subendothelial LDL concentrations at plaque locations were,
      on average, 45% (RCA) and 187% (LCA) higher than the respective average
      subendothelial concentration. Our results demonstrate that locally elevated
      subendothelial LDL concentration correlates with subsequent plaque formation at
      the same location.

PMID- 21723557
TI  - Coupling plowing of cartilage explants with gene expression in models for
      synovial joints.
AB  - Articular cartilage undergoes complex loading modalities generally including
      sliding, rolling and plowing (i.e. the compression by a condyle normally to the
      tissue surface under simultaneously tangential displacement, thus generating a
      tractional force due to tissue deformation). Although in in vivo studies it was
      shown that excessive plowing can lead to osteoarthritis, little quantitative
      experimental work on this loading modality and its mechanobiological effects is
      available in the literature. Therefore, a rolling/plowing explant test system has
      been developed to study the effect on pristine cartilage of plowing at different
      perpendicular forces. Cartilage strips harvested from bovine nasal septa of 12
      months-old calves were subjected for 2h to a plowing-regime with indenter normal
      force of 50 or 100 N and a sliding speed of 10 mm s(-1). 50 N produced a
      tractional force of 1.2+/-0.3N, whereas 100 N generated a tractional force of
      8.0+/-1.4N. Furthermore, quantitative-real-time polymerase chain reaction
      experiments showed that TIMP-1 was 2.5x up-regulated after 50 N plowing and 2x
      after 100 N plowing, indicating an ongoing remodeling process. The expression of
      collagen type-I was not affected after 50 N plowing but it was up-regulated
      (6.6x) after 100 N plowing, suggesting a possible progression to an injury stage
      of the cartilage, as previously reported in cartilage of osteoarthritic patients.
      We conclude that plowing as performed by our mimetic system at the chosen
      experimental parameters induces changes in gene expression depending on the
      tractional force, which, in turn, relates to the applied normal force.

PMID- 21723558
TI  - An induced acceleration index for examining joint couplings.
AB  - A muscle produces moments at the joints it crosses, but these moments can also
      cause accelerations at joints not crossed by the muscle. This phenomenon, the
      acceleration of a joint caused by a muscle not crossing the joint, is referred to
      as induced acceleration. For a system of rigid bodies this study examines how
      system configuration, and segmental inertial properties dictate the potential of
      one joint to cause the acceleration of other joints in the system. From the
      equations of motion for a series of rigid bodies, an induced acceleration index
      (IAI) was developed. The IAI permits quantification of the relative potential of
      moments produced at joints in the kinematic chain to accelerate other joints in
      the kinematic chain. The IAI is a function of system orientation, segment
      lengths, and inertial properties. The IAI was used to examine the roles of the
      ankle and hip joints in quiet standing. The ankle joint had over 12 times the
      ability to accelerate the hip joint, than the hip had to accelerate the ankle
      joint. These results in part explain the relative merits of the two strategies
      predominantly used to maintain upright stance: the ankle and hip strategies. This
      index permits an understanding of how the induced accelerations are dependent on
      system configuration and inertial properties. The IAI is also useful in
      situations where the inertial properties of the system under investigation
      changes, for example due to the fitting of a new prostheses to a trans-tibial
      amputee.

PMID- 21723559
TI  - Large pore volume mesoporous copper particles and scaffold microporous carbon
      material obtained from an inorganic-organic nanohybrid material, copper-succinate
      layered hydroxide.
AB  - Copper-succinate-layered hydroxide (CSLH), a new nanohybrid material, was
      synthesized as an inorganic-organic nanohybrid, in which organic moiety was
      intercalated between the layers of a single cation layered material, copper
      hydroxide nitrate. Microporous scaffold carbon material was obtained by thermal
      decomposition of the nanohybrid at 500  degrees C under argon atmosphere followed
      by acid washing process. Furthermore, the heat-treated product of the nanohybrid
      at 600  degrees C was ultrafine mesoporous metallic copper particles. The results
      of this study confirmed the great potential of CSLH to produce the carbon
      material with large surface area (580 m(2)/g) and high pore volume copper powder
      (2.04 cm(3)/g).

PMID- 21723560
TI  - Finite-amplitude dynamics of coupled cylindrical menisci.
AB  - The cylindrical meniscus is a liquid/gas interface of circular-cap cross-section
      constrained along its axis and bounded by end-planes. The inviscid motions of
      coupled cylindrical menisci are studied here. Motions result from the competition
      between inertia and surface tension forces. Restriction to shapes that are of
      circular-cap cross-section leads to an ordinary differential equation (ode)
      model, with the advantage that finite-amplitude stability can be examined. The
      second-order nonlinear ode model has a Hamiltonian structure, showing dynamical
      behavior like the Duffing-oscillator. The energy landscape has either a single-
      or double-welled potential depending on the extent of volume overfill. Total
      liquid volume is a bifurcation parameter, as in the corresponding problem for
      coupled spherical-cap droplets. Unlike the spherical-cap problem, however, axial
      disturbances can also destabilize, depending on overfill. For large volumes,
      previously known axial stability results are applied to find the limit at which
      axial symmetry is lost and comparison is made to the Plateau-Rayleigh limit.

PMID- 21723561
TI  - Block copolymer micellization induced microphase mass transfer: partition of
      Pd(II), Pt(IV) and Rh(III) in three-liquid-phase systems of S201-EOPO-Na2SO4-H2O.
AB  - Three-liquid-phase partitioning of Pd(II), Pt(IV) and Rh(III) in systems of
      S201(diisoamyl sulfide)/nonane-EOPO(polyethylene oxide-polypropylene oxide random
      block copolymer)-Na(2)SO(4)-H(2)O was investigated. Experimental results
      indicated that the selective enrichment of Pd(II), Pt(IV) and Rh(III)
      respectively into the S201 organic top phase, EOPO-based middle phase and
      Na(2)SO(4) bottom phase was achieved by control over the phase behavior of the
      three-liquid-phase systems (TLPS). The microphase mass transfer behavior of
      Pt(IV), Pd(II) and Rh(III) was closely related to the micellization of EOPO
      molecules. A suggested micro-mechanism model and a mass transfer model describe
      the micellization of EOPO molecules and the effect on mass transfer of platinum
      ions across the microphase interfaces. The salting-out induced continuous
      dehydration and ordered arrangement of the hydrophilic PEO segments in
      amphiphilic EOPO micelle, and these are the main driving forces for mass transfer
      of platinum metal ions onto the exposed activity sites of the dehydrated PEO
      segments. The differences in microphase interfacial structure of EOPO micelles
      are crucial for the efficient separation between Pt(IV), Pd(II) and Rh(III).

PMID- 21723562
TI  - Dynamics of Pseudomonas aeruginosa association with anionic hydrogel surfaces in
      the presence of aqueous divalent-cation salts.
AB  - Binding of bacteria to solid surfaces is complex with many aspects incompletely
      understood. We investigate Pseudomonas aeruginosa uptake kinetics onto hydrogel
      surfaces representative of soft-contact lenses made of nonionic poly(2
      hydroxyethylmethacrylate) (p-HEMA), anionic poly(methacrylic acid) (p-MAA), and
      anionic poly(acrylic acid) (p-AA). Using a parallel-plate flow cell under phase
      contrast microscopy, we document a kinetic "burst" at the anionic hydrogel
      surface: dilute aqueous P. aeruginosa first rapidly accumulates and then rapidly
      depletes. Upon continuing flow, divalent cations in the suspending solution sorb
      into the hydrogel network causing the previously surface-accumulated bacteria to
      desorb. The number of bacteria eventually bound to the surface is low compared to
      the nonionic p-HEMA hydrogel. We propose that the kinetic burst is due to
      reversible divalent-cation bridging between the anionic bacteria and the
      negatively charged hydrogel surface. The number of surface bridging sites
      diminishes as divalent cations impregnate into and collapse the gel. P.
      aeruginosa association with the surface then falls. Low eventual binding of P.
      aeruginosa to the anionic hydrogel is ascribed to increased surface
      hydrophilicity compared to the counterpart nonionic p-HEMA hydrogel.

PMID- 21723563
TI  - Two-component supramolecular organogels formed by maleic N-monoalkylamides and
      aliphatic amines.
AB  - The complexes of maleic N-monoalkylamides and aliphatic amines lead to the
      formation of sheet-like and fiber-shaped aggregates in diverse organic solvents.
      Their morphologies and microstructures were characterized by Fourier transform
      infrared spectroscopy (FT-IR), scanning electron microscope (SEM), as well as
      small angle X-ray diffraction (SA-XRD). The results reveal that the alkyl chain
      lengths of 8-12 carbons for maleic N-monoalkylamides, and 12-18 carbons for
      aliphatic amines, are suitable for obtaining highly efficient two-component
      gelators.

PMID- 21723564
TI  - Ionic liquid-based stable nanofluids containing gold nanoparticles.
AB  - A one-phase and/or two-phase method were used to prepare the stable ionic liquid
      based nanofluids containing same volume fraction but different sizes or surface
      states of gold nanoparticles (Au NPs) and their thermal conductivities were
      investigated in more detail. Five significant experiment parameters, i.e.
      temperature, dispersion condition, particle size and surface state, and viscosity
      of base liquid, were evaluated to supply experimental explanations for heat
      transport mechanisms. The conspicuously temperature-dependent and greatly
      enhanced thermal conductivity under high temperatures verify that Brownian motion
      should be one key effect factor in the heat transport processes of ionic liquid
      based gold nanofluids. While the positive influences of proper aggregation and
      the optimized particle size on their thermal conductivity enhancements under some
      specific conditions demonstrate that clustering may be another critical effect
      factor in heat transport processes. Moreover, the remarkable difference of the
      thermal conductivity enhancements of the nanofluids containing Au NPs with
      different surface states could be attributed to the surface state which has a
      strong correlation with not only Brownian motion but also clustering. Whilst the
      close relationship between their thermal conductivity enhancements and the
      viscosity of base liquid further indicate Brownian motion must occupy the leading
      position among various influencing factors. Finally, a promisingly synergistic
      effect of Brownian motion and clustering based on experimental clues and
      theoretical analyses was first proposed, justifying different mechanisms are sure
      related. The results may shed lights on comprehensive understanding of heat
      transport mechanisms in nanofluids.

PMID- 21723565
TI  - Impact of prenatal exposure to cocaine and tobacco on diffusion tensor imaging
      and sensation seeking in adolescents.
AB  - OBJECTIVE: To study white matter integrity with diffusion tensor imaging in
      adolescents with prenatal cocaine exposure, tobacco exposure, or both. STUDY
      DESIGN: Subjects included 20 adolescents with prenatal cocaine exposure (15 with
      tobacco exposure) and 20 non-cocaine-exposed subjects (8 with tobacco exposure).
      Diffusion tensor imaging measures were assessed in 5 subregions of the corpus
      callosum. The Sensation Seeking Scale for Children was administered to evaluate
      behavioral inhibition. RESULTS: No significant differences were found between the
      cocaine-exposed and non-cocaine-exposed groups in each subregion of the corpus
      callosum on measures of fractional anisotropy (FA) and mean diffusivity, although
      the cocaine-exposed group showed a trend (P = .06) toward higher FA in
      projections to the supplementary motor area and premotor cortex. Prenatal tobacco
      exposure was associated with decreased FA in the supplementary motor area and
      premotor cortex projections after adjustment for relevant co-variates (P = .03).
      Decreased FA was related to more sensation seeking in the adolescents who were
      prenatally exposed to tobacco. CONCLUSION: Prenatal tobacco exposure could affect
      white matter integrity, which is related to sensation seeking in adolescents.
      Developmental neurotoxins might have differential influences on white matter
      maturation in adolescence.

PMID- 21723566
TI  - Waist-to-height ratio is not a predictor of systolic blood pressure in 3-year-old
      children.
AB  - Waist:height has been proposed as an indicator of cardiovascular risk. We
      investigated the association of waist:height with systolic BP (sBP) in 3 year old
      children. Body mass index was a significant predictor of sBP, whereas
      waist:height was not: suggesting waist:height is not a useful indicator of sBP in
      this age group.

PMID- 21723567
TI  - Vitamin D-mediated immune regulation in multiple sclerosis.
AB  - Although Vitamin D is best known as a modulator of calcium homeostasis, it also
      has immune modulating potential. A protective effect of Vitamin D on Multiple
      Sclerosis (MS) is supported by the reduced risk associated with sun exposure and
      use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have
      been associated with lower risk of MS. To gain more insight into putative
      regulatory mechanisms of Vitamin D in MS pathogenesis, we studied 132 Hispanic
      patients with clinically definite MS, 58 with relapsing remitting MS (RR MS)
      during remission, 34 RR MS patients during relapse, and 40 primary progressive MS
      cases (PP MS). Sixty healthy individuals matched with respect to place of
      residence, race/ethnicity, age and gender served as controls. Levels of 25(OH)
      Vitamin D and 1,25(OH)(2) Vitamin D, measured by ELISA were significantly lower
      in RR MS patients than in controls. In addition, levels in patients suffering
      relapses were lower than during remissions. By contrast, PP MS patients showed
      similar values to controls. Proliferation of both freshly isolated CD4+ T cells
      and MBP-specific T cells was significantly inhibited by 1,25(OH)(2) Vitamin D.
      Moreover, activated Vitamin D enhanced the development of IL-10 producing cells,
      and reduced the number of IL-6 and IL-17 secreting cells. Notably, VDR expression
      was induced by 1,25(OH)(2) Vitamin D in both activated and resting cells.
      Interestingly, T cells were able to metabolize 25(OH) Vitamin D into biologically
      active 1,25(OH)(2) Vitamin D, since T cells express 1alpha-hydroxylase
      constitutively. Finally, 1,25(OH)(2) Vitamin D also increased the expression and
      biological activity of IDO, triggering significant increase in the number of
      CD4+CD25+ T regulatory cells. Collectively, these findings suggest that
      1,25(OH)(2) VitaminD plays an important role in T cell homeostasis during the
      course of MS, suggesting correction of its deficiency may be useful during
      treatment of the disease.

PMID- 21723568
TI  - Sexual problems in Parkinson's disease: the multidimensional nature of the
      problem and of the intervention.
AB  - Sexual problems are common in Parkinson's disease and contribute to poor quality
      of life of patients and partners. Nonmotor and motor disease manifestations can
      affect sexual function. This article reviews the progressive and multidimensional
      sexual manifestations and provides practical suggestions for taking sexual
      history and treating sexual problems, which may enable clinicians to contribute
      to the sexual wellbeing of patients.

PMID- 21723569
TI  - Are metal-induced hypersensitivities in harbor seals associated with liver
      function?
AB  - Environmental exposure to metals is believed to affect marine mammal health
      adversely including immunosuppression or acute as well as chronic inflammatory
      processes leading to hypersensitivities or autoimmune diseases. Metal-specific
      hypersensitivities were found in several pinnipeds of the North Sea. However,
      hypersensitivity is a complex phenomenon whose characteristics are still not
      completely understood; in particular, effects on health are not well established.
      In the present study, we compared basic hematological and biochemical parameters
      of seals with and without metal-specific hypersensitivities. We found altered
      hematological parameters and liver enzyme patterns in seals with a metal-induced
      hypersensitivity, including a reduction in macrophages, an increase in
      lymphocytes, and elevated levels of lactate dehydrogenase. These findings support
      the suggestion of a chronic influence of metal pollutants on the health of marine
      mammals of the North Sea.

PMID- 21723571
TI  - Compliance with a healthy lifestyle in a representative sample of the Greek
      population: preliminary results of the Hellas Health I study.
AB  - OBJECTIVES: To investigate lifestyle health behaviours, such as smoking, physical
      activity, weight status and dietary habits, in a representative sample of the
      adult Greek population. STUDY DESIGN: Cross-sectional, household interviews
      (Hellas Health I survey, 2006). METHODS: A stratified representative sample (n =
      1005, 483 males, 522 females) of the Greek adult population (mean age 47.39
      years, median age 46 years, range 18-99 years) was interviewed. Self-reported
      demographic and lifestyle behaviour data were obtained. The Food Frequency
      Questionnaire (FFQ) was used to record dietary habits, and a Mediterranean score
      was derived from the FFQ to assess adherence to the Mediterranean diet. A higher
      Mediterranean score indicates greater adherence to the Mediterranean diet.
      Physical activity was evaluated using the International Physical Activity
      Questionnaire. RESULTS: Smoking is highly prevalent in the Greek population
      (43.1%), particularly among people aged 18-36 (52.9%) and 37-56 years (51.9%).
      Smoking prevalence was 52.4% in men and 34.5% in women (P < 0.001). In total,
      54.1% of men and 45.3% of women were classified as physically active (P = 0.007).
      The proportion of physically active subjects decreased with age (P for
      trend<0.001). The prevalence of obesity was higher in women (18.3%) than men
      (14.3%, P < 0.001), and increased with age (P for trend<0.001). Men were found to
      have higher Mediterranean scores than women (27.09 vs 26.14, P < 0.05). Dietary
      habits also differed between younger and older participants, and the
      Mediterranean score increased with age. CONCLUSIONS: The prevalence rates for
      smoking, physical inactivity and obesity are high, and compliance with the
      Mediterranean diet is low in Greece. Nationwide interventions focused on health
      promotion and primary prevention are urgently needed.

PMID- 21723570
TI  - Ecological status of seagrass ecosystems: An uncertainty analysis of the meadow
      classification based on the Posidonia oceanica multivariate index (POMI).
AB  - Quantifying the uncertainty associated with monitoring protocols is essential to
      prevent the misclassification of ecological status and to improve sampling
      design. We assessed the Posidonia oceanica multivariate index (POMI) bio
      monitoring program for its robustness in classifying the ecological status of
      coastal waters within the Water Framework Directive. We used a 7-year data set
      covering 30 sites along 500 km of the Catalonian coastline to examine which
      version of POMI (14 or 9 metrics) maximises precision in classifying the
      ecological status of meadows. Five factors (zones within a site, sites within a
      water body, depth, years and surveyors) that potentially generate classification
      uncertainty were examined in detail. Of these, depth was a major source of
      uncertainty, while all the remaining spatial and temporal factors displayed low
      variability. POMI 9 matched POMI 14 in all factors, and could effectively replace
      it in future monitoring programs.

PMID- 21723572
TI  - [Fusiform aneurysmal dilation of the bowel in a metastasis from a cutaneous
      melanoma].

PMID- 21723573
TI  - Nationwide Cyprinid herpesvirus 3 contamination in natural rivers of Japan.
AB  - Cyprinid herpesvirus 3 (CyHV-3) disease is a significant threat for common and
      koi carp cultivators and for freshwater ecosystems. To determine the prevalence
      of CyHV-3 in Japanese rivers, a nationwide survey of all national class-A rivers
      was undertaken in the Summer of 2008. The virus was concentrated from river water
      samples using the cation-coated filter method. CyHV-3 DNA was detected in 90
      rivers, representing 90% of 103 successfully analysed rivers. More than 100,000
      copies of CyHV-3 DNA per litre of sample were detected in four rivers, higher
      than that reported during the Yura River outbreak in 2007. For CyHV-3-positive
      rivers, the log CyHV-3 density was negatively correlated with the water
      temperature on the sampling date and positively correlated with the suspended
      solids and dissolved oxygen, which are annually averaged for each river. Our
      results demonstrate that virus detection using molecular biology techniques is a
      powerful tool for monitoring the presence of CyHV-3 in natural environments.

PMID- 21723574
TI  - Isolation and phylogenetic analysis of pandemic H1N1/09 influenza virus from
      swine in Jiangsu province of China.
AB  - To investigate whether the 2009 pandemic H1N1 influenza A virus was still being
      transmitted in swine, a total of 1029 nasal swab samples from healthy swine were
      collected from January to May 2010 in Jiangsu province of China. Eight H1N1
      influenza viruses were isolated and identified, and their full length genomes
      were sequenced. We found that all eight of the H1N1 viruses shared higher than
      98.0% sequence identity with the 2009 pandemic virus A/Jiangsu/1/2009 (JS1). In
      addition, some of these viruses had D225G (3/8) mutations in the receptor binding
      sites of the hemagglutinin (HA) protein, indicating enhancement of their binding
      affinity to the sialic alpha2, 3Gal receptor. In conclusion, the 2009 pandemic
      H1N1 influenza A virus has retro-infected swine from humans in mainland China,
      and significant viral evolution is still ongoing in this species.

PMID- 21723575
TI  - Comparison of a nucleoprotein gene based RT-PCR with real time RT-PCR for
      diagnosis of avian influenza in clinical specimens.
AB  - A nucleoprotein (NP) gene based reverse transcription polymerase chain reaction
      (npRT-PCR) assay was developed in our laboratory which could detect 35.09% of the
      experimental samples negative for virus isolation in first passage but positive
      by third passage. Reducing the reaction volume to 12.5 MUl did not alter the test
      sensitivity and the results did not vary when duplicate samples were run in a
      different thermal cycler. The positive and negative agreements of this test in
      clinical specimens were compared with a matrix gene based real time RT-PCR with
      virus isolation as standard. A total of 516 clinical specimens including tissues,
      swabs and feces submitted from various States of India as part of active
      surveillance for avian influenza were tested by npRT-PCR, RRT-PCR and virus
      isolation in 9-11 day old embryonated specific pathogen free chicken eggs. The
      positive and negative agreements of npRT-PCR with virus isolation were found to
      be 0.909+/-0.022 and 0.980+/-0.004 respectively and that of RRT-PCR with virus
      isolation were 0.902+/-0.023 and 0.977+/-0.005 respectively. Since the positive
      and negative agreements of both npRT-PCR and RRT-PCR tests were similar, we
      suggest that this test can be used by peripheral veterinary laboratories that do
      not have real time PCR facility for active surveillance of AIV.

PMID- 21723576
TI  - Reappraisal of the immunopathogenesis of disseminated leishmaniasis: in situ and
      systemic immune response.
AB  - Disseminated leishmaniasis (DL) is an emerging form of Leishmania braziliensis
      infection characterised by multiple cutaneous lesions on different parts of the
      body and a high rate of mucosal involvement. Systemic production of TNFalpha and
      IFNgamma in DL patients is lower than in cutaneous leishmaniasis (CL) caused by
      L. braziliensis, which may account for parasite dissemination due to the
      decreased ability to control parasite growth. In this study, the systemic and in
      situ immune response of DL and CL patients was characterised through evaluation
      of chemokine and cytokine production. In situ evaluation showed similar
      production of IFNgamma, TNFalpha, IL-10, transforming growth factor-beta
      (TGFbeta), chemokine (C-C motif) ligand 2 (CCL2), CCL3, CCL11 and chemokine (C-X
      C motif) ligand 10 (CXCL10) in papular and ulcerative lesions from DL as well as
      in ulcerated lesions from CL. Serum levels of CXCL9, a chemokine that attracts T
      cells, was higher in serum from DL than from CL. These data indicate that a
      decrease in the type 1 immune response in peripheral blood of DL patients is due
      to attraction of Leishmania antigen-activated T-cells to the multiple cutaneous
      lesions. This may account for the absence of or few parasites in the lesions and
      for the development of ulcers similar to those observed in CL.

PMID- 21723577
TI  - De chirigis senilibus academiae.

PMID- 21723578
TI  - Exact second order formalism for the study of electro-acoustic properties in
      piezoelectric structures under an initial mechanical stress.
AB  - In this study we develop the exact second order formalism of piezoelectric
      structures under an external mechanical stress. Indeed, previous models are
      approximated since they consist in deriving all the equations in the natural
      coordinate system (corresponding to the pre-stress free case). Hence, our exact
      formalism proposes to obtain the whole of equations in the current coordinate
      system (which is the coordinate system after the pre-deformation). Then, this
      exact formalism is used to derive the modified Christoffel equations and the
      modified KLM model. Finally, we quantify the correction with the approximate
      formalism on several transfer functions and electro-mechanical parameters for a
      non hysteretic material (lithium niobate). In conclusion, we show that for this
      material, significant corrections are obtained when studying the plane wave
      velocities and the electrical input impedance (about 4%), whereas other
      parameters such as coupling coefficient and impulse response are less influenced
      by the choice of coordinate systems (corrections less than 0.5%).

PMID- 21723579
TI  - Infectious bursal disease virus activates the phosphatidylinositol 3-kinase
      (PI3K)/Akt signaling pathway by interaction of VP5 protein with the p85alpha
      subunit of PI3K.
AB  - Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is commonly activated upon
      virus infection and has been implicated in the regulation of diverse cellular
      functions such as proliferation and apoptosis. The present study demonstrated for
      the first time that infectious bursal disease virus (IBDV), the causative agent
      of a highly contagious disease in chickens, can induce Akt phosphorylation in
      cultured cells, by a mechanism that is dependent on PI3K. Inhibition of PI3K
      activation greatly enhanced virus-induced cytopathic effect and apoptotic cell
      death as evidenced by cleavage of poly-ADP ribose polymerase and activation of
      caspase-3. Investigations into the mechanism of PI3K/Akt activation revealed that
      IBDV activates PI3K/Akt signaling through binding of the non-structural protein
      VP5 to regulatory subunit p85alpha of PI3K resulting in the suppression of
      premature apoptosis and improved virus growth after infection. The results
      presented here provide a basis for understanding molecular mechanism of IBDV
      infection.

PMID- 21723580
TI  - Molecular evolution of West Nile virus in a northern temperate region:
      Connecticut, USA 1999-2008.
AB  - West Nile virus (WNV) has become firmly established in northeastern US,
      reemerging every summer since its introduction into North America in 1999. To
      determine whether WNV overwinters locally or is reseeded annually, we examined
      the patterns of viral lineage persistence and replacement in Connecticut over 10
      consecutive transmission seasons by phylogenetic analysis. In addition, we
      compared the full protein coding sequence among WNV isolates to search for
      evidence of convergent and adaptive evolution. Viruses sampled from Connecticut
      segregated into a number of well-supported subclades by year of isolation with
      few clades persisting >=2 years. Similar viral strains were dispersed in
      different locations across the state and divergent strains appeared within a
      single location during a single transmission season, implying widespread movement
      and rapid colonization of virus. Numerous amino acid substitutions arose in the
      population but only one change, V->A at position 159 of the envelope protein,
      became permanently fixed. Several instances of parallel evolution were identified
      in independent lineages, including one amino acid change in the NS4A protein that
      appears to be positively selected. Our results suggest that annual reemergence of
      WNV is driven by both reintroduction and local-overwintering of virus. Despite
      ongoing evolution of WNV, most amino acid variants occurred at low frequencies
      and were transient in the virus population.

PMID- 21723581
TI  - Kinetics of model high molecular weight organic compounds biodegradation in soil
      aquifer treatment.
AB  - Soil Aquifer Treatment (SAT) is a process where treated wastewater is purified
      during transport through unsaturated and saturated zones. Easily biodegradable
      compounds are rapidly removed in the unsaturated zone and the residual organic
      carbon is comprised of primarily high molecular weight compounds. This research
      focuses on flow in the saturated zone where flow conditions are predictable and
      high molecular weight compounds are degraded. Flow through the saturated zone was
      investigated with 4 reactors packed with 2 different particle sizes and operated
      at 4 different flow rates. The objective was to evaluate the kinetics of
      transformation for high molecular weight organics during SAT. Dextran was used as
      a model compound to eliminate the complexity associated with studying a mixture
      of high molecular weight organics. The hydrolysis products of dextran are easily
      degradable sugars. Batch experiments with media taken from the reactors were used
      to determine the distribution of microbial activity in the reactors. Zero-order
      kinetics were observed for the removal of dextran in batch experiments which is
      consistent with hydrolysis of high molecular weight organics where extracellular
      enzymes limit the substrate utilization rate. Biomass and microbial activity
      measurements demonstrated that the biomass was independent of position in the
      reactors. A Monod based substrate/biomass growth kinetic model predicted the
      performance of dextran removal in the reactors. The rate limiting step appears to
      be hydrolysis and the overall rate was not affected by surface area even though
      greater biomass accumulation occurred as the surface area decreased.

PMID- 21723582
TI  - Determination of sorption of seventy-five pharmaceuticals in sewage sludge.
AB  - Sorption of 75 active pharmaceutical ingredients (APIs) to three different types
      of sludge (primary sludge, secondary sludge with short and long sludge age
      respectively) were investigated. To obtain the sorption isotherms batch studies
      with the APIs mixture were performed in four nominal concentrations to water
      containing 1 g of sludge. The range of APIs concentrations was between ng L(-1)
      to MUg L(-1) which are found in the wastewater effluents. Isotherms were obtained
      for approximately 45 of the APIs, providing distribution coefficients for linear
      (Kd), Freundlich (Kf) and Langmuir (KL) isotherms. Kd, Kf and KL ranging between
      7.1*10(4) and 3.8*10(7), 1.1*10(-2) and 6.1*10(4) and 9.2*10(-3) and 1.1 L kg(
      1), respectively. The obtained coefficients were applied to estimate the fraction
      of APIs in the water phase (see Abstract Graphic). For 37 of the 75 APIs, the
      predicted presence in the liquid phase was estimated to >80%. 24 APIs were
      estimated to be present in the liquid phase between 20 and 80%, and 14 APIs were
      found to have <20% presence in the liquid phase, i.e. high affinity towards
      sludge. Furthermore, the effect of pH at values 6, 7 and 8 was evaluated using
      one way ANOVA-test. A significant difference in Kds due to pH changes were found
      for 6 of the APIs (variation 10-20%).

PMID- 21723583
TI  - Comparative toxicity of a brominated flame retardant (tetrabromobisphenol A) on
      microalgae with single and multi-species bioassays.
AB  - The potential threat of emerging chemicals to the aquatic flora is a major issue.
      The purpose of the study was to develop a multispecies microalgae test in order
      to determine the impact of species interactions on the cytoxicity of an emergent
      toxic contaminant: the tetrabromobisphenol A (TBBPA). Single and multi-species
      tests were thus performed to study the effects of this flame retardant on two
      microalgae (Pseudokirchneriella subcapitata and Nitzschia palea) commonly
      observed in freshwater. A synthetic medium was designed to allow the growth of
      both species. The algae were exposed to 1.8, 4.8, 9.2, 12.9 and 16.5 MUM of TBBPA
      for 72 h. After staining with fluorescein diacetate (FDA), viable cells of each
      alga species were analyzed by flow cytometry based on chlorophyll
      autofluorescence and intracellular esterase activity. Density and abundance of
      viable cells were assessed to follow the population growth and the cell
      viability. In TBBPA treated samples, the growth of the two microalgae was
      significantly inhibited at the three highest concentrations (9.2, 12.9 and 16.5
      MUM) in the two tests. At the end of the experiment (t=72 h), the cell viability
      was also significantly smaller at these concentrations. The decreases of growth
      rate and viable cell abundance in TBBPA treated populations of N. palea were
      significantly higher in multi-species test in comparison with the single-species
      test. No significant differences were noticed between the two tests for P.
      subcapitata populations exposed to TBBPA.

PMID- 21723584
TI  - Validation of a GC-MS/MS method for simultaneous determination of 86 persistent
      organic pollutants in marine sediments by pressurized liquid extraction followed
      by stir bar sorptive extraction.
AB  - A multiresidue method for the analysis of 86 persistent pollutants in marine
      sediments at ultra-trace level has been developed and validated using pressurized
      liquid extraction (PLE) and stir-bar sorptive extraction (SBSE) coupled with
      thermal desorption and gas chromatography-triple quadrupole mass spectrometry (TD
      GC-MS/MS QqQ). The compounds analyzed belong to various families such as
      polychlorinated biphenyls, polycyclic aromatic hydrocarbons, polybrominated
      diphenylethers, organophosphorus and organochlorine pesticides and other
      pesticides such as urons, and triazines. The analytes have very different
      polarities and log K(ow) values, which is an important parameter in the
      optimization of a SBSE method. Due to PLE high efficiency and throughput rates,
      along with the proven ability for multiresidue analysis and excellent sensitivity
      of SBSE, we present an efficient method. The limits of quantification obtained
      ranged from 0.014 to 1.0 ng g(-1), with detection limits below pg g(-1) levels.
      In order to validate the proposed methodology, quality parameters such as
      recovery, linearity and reproducibility were studied. Recoveries ranged from 63%
      to 119%, reproducibility (in terms of Relative Standard Deviation for ten
      determinations) was lower than 35% in all cases, and determination coefficients
      higher than 0.990 for all analytes. The main factors that affect PLE, SBSE and GC
      MS/MS procedures were optimized. The method was applied to the analysis of nine
      marine sediments obtained from the nine main submarine wastewater discharge
      points (emissaries) presents along the coast of Tenerife Island (Canary Islands,
      Spain).

PMID- 21723585
TI  - Comparison of the concentrations of polychlorinated biphenyls and dioxins in
      mothers affected by the Yusho incident and their children.
AB  - Accumulated maternal dioxins are passed onto the fetus and neonate via the
      placenta and maternal milk. In Japan in 1968, an accidental human exposure to
      rice oil contaminated with polychlorinated biphenyls (PCBs) and other dioxin
      related compounds, such as polychlorinated dibenzofurans (PCDFs), led to
      development of Yusho oil disease. We investigated differences in blood dioxin
      concentrations in mother-children pairs affected by the Yusho incident. From 2002
      to 2008, blood samples were collected from 26 pairs of Yusho mothers and their
      children (19 mothers, 26 children). Specific congeners of seven polychlorinated
      dibenzo-p-dioxins (PCDDs), ten PCDFs, and four non-ortho PCBs were analyzed. The
      children had significantly lower TEQ concentrations of PCDDs, PCDFs, and coplanar
      PCBs compared to their mothers. The mother-child difference in blood
      concentrations varied with the congeners; the largest for 2,3,4,7,8-pentaCDF and
      the smallest for 1,2,3,4,6,7,8-heptaCDD. The level for 2,3,4,7,8-pentaCDF, which
      characterizes Yusho oil disease, was approximately 17-30 times higher in the
      mothers than in the general population, whereas there were no significant
      differences between children in the formula-fed group and the general population.
      In contrast, the mean level for 2,3,4,7,8-pentaCDF in the breast-fed group was
      approximately 1.5 times, (range 0.5-6.5 times) higher than that in the general
      population. Over 30 years after the Yusho incident, the mean blood dioxin levels
      in the offspring were only a fraction of the levels in their mothers. This is
      more consistent with exposure via breast milk than via transplacental transfer in
      the Yusho incident.

PMID- 21723586
TI  - Cd-induced changes in leaf proteome of the hyperaccumulator plant Phytolacca
      americana.
AB  - Cadmium (Cd) is highly toxic to all organisms. Soil contamination by Cd has
      become an increasing problem worldwide due to the intensive use of Cd-containing
      phosphate fertilizers and industrial zinc mining. Phytolacca americana L. is a Cd
      hyperaccumulator plant that can grow in Cd-polluted areas. However, the molecular
      basis for its remarkable Cd resistance is not known. In this study, the effects
      of Cd exposure on protein expression patterns in P.americana was investigated by
      2-dimensional gel electrophoresis (2-DE). 2-DE profiles of leaf proteins from
      both control and Cd-treated (400MUM, 48h) seedlings were compared quantitatively
      using ImageMaster software. In total, 32 differentially expressed protein spots
      were identified using MALDI-TOF/TOF mass spectrometry coupled to protein database
      search, corresponding to 25 unique gene products. Of those 14 were
      enhanced/induced while 11 reduced under Cd treatment. The alteration pattern of
      protein expression was verified for several key proteins involved in distinct
      metabolic pathways by immuno-blot analysis. Major changes were found for the
      proteins involved in photosynthetic pathways as well as in the sulfur- and GSH
      related metabolisms. One-third of the up-regulated proteins were attributed to
      transcription, translation and molecular chaperones including a protein belonging
      to the calreticulin family. Other proteins include antioxidative enzymes such as
      2-cys-peroxidase and oxidoreductases. The results of this proteomic analysis
      provide the first and primary information regarding the molecular basis of Cd
      hypertolerance in P. americana.

PMID- 21723587
TI  - Polybrominated diphenyl ethers in various atmospheric environments of Taiwan:
      their levels, source identification and influence of combustion sources.
AB  - In this study, ambient air samples from different atmospheric environments were
      examined for both PBDE and PCDD/F characteristics to verify that combustion is a
      significant PBDE emission source. The mean +/- SD atmospheric PBDE concentrations
      were 165 +/- 65.0 pg Nm(-3) in the heavy steel complex area and 93.9 +/- 24.5 pg
      Nm(-3) in the metals complex areas, 4.7 and 2.7 times higher than that (35.3 +/-
      15.5 pg Nm(-3)) in the urban areas, respectively. The statistically high
      correlation (r=0.871, p<0.001) found between the atmospheric PBDE and PCDD/F
      concentrations reveals that the combustion sources are the most likely PBDE
      emission sources. Correspondence analysis shows the atmospheric PBDEs of the
      heavy steel and metals complex areas are associated with BDE-209, -203, -207, 
      208, indicative of combustion source contributions. Furthermore, the PBDEs in
      urban ambient air experience the influence of the evaporative releases of the
      commercial penta- and octa-BDE mixtures, as well as combustion source emissions.
      By comparing the PBDE homologues of indoor air, urban ambient air, and stack flue
      gases of combustion sources, we found that the lighter brominated PBDEs in urban
      ambient air were contributed by the indoor air, while their highly brominated
      ones were from the combustion sources, such as vehicles. The developed source
      identification measure can be used to clarify possible PBDE sources not only for
      Taiwanese atmosphere but also for other environmental media in other countries
      associated with various emission sources in the future.

PMID- 21723588
TI  - Elaborations on the use of the ecosystem services concept for application in
      ecological risk assessment for soils.
AB  - This paper describes scientific developments that have raised awareness that
      changes in ecological risk assessment (ERA) methods are necessary. These changes
      have also been triggered by developments in environmental policies. This is
      illustrated by examples for The Netherlands and Europe. The ecosystem services
      concept seems to gain a central role in developments of new ERA methods. Main
      reasons for this are the integrative character of the concept, making it possible
      to integrate over environmental compartments or over environmental assessment
      methods, the concept's strength as communication tool and the possibility to
      value ecosystem services in economic terms. A method using ecosystem services in
      ERA is presented here in more detail, as an example. In this method assessment
      endpoints are derived from structures and processes in the ecosystem that are
      considered indispensable for the provision of particular ecosystem services. The
      approach facilitates fine-tuning ERA to specific land use demands.

PMID- 21723589
TI  - Association between urinary arsenic and diabetes mellitus in the Korean general
      population according to KNHANES 2008.
AB  - INTRODUCTION: We present data from the Korean National Health and Nutrition
      Examination Survey (KNHANES) 2008 on the associations between urinary arsenic and
      diabetes mellitus in a representative sample of the adult Korean population.
      METHODS: This study was based on data obtained in KNHANES 2008, which was
      conducted for three years (2007-2009) using a rolling sampling design involving a
      complex, stratified, multistage, probability-cluster survey of a representative
      sample of the noninstitutionalized civilian population of South Korea. RESULTS:
      Geometric means of total urinary arsenic concentration in females and total
      participants with diabetes mellitus were significantly higher than in
      participants without diabetes mellitus after adjustment for covariates, including
      age, seafood consumption, body mass index (BMI), hypertension, area of residence,
      regional area, education level, and smoking and drinking status. Multiple
      regression analysis after similar adjustment showed that total urinary arsenic
      concentration was associated with diabetes status in the females and total
      participants. In addition, after similar adjustment, the odds ratios (ORs) for
      diabetes mellitus in female participants and all participants were 1.502 (95% CI,
      1.038-2.171) and 1.312 (95% CI, 1.040-1.655), respectively, for doubling of the
      level of urinary total arsenic concentration. CONCLUSION: This study showed an
      association between total urinary arsenic concentration and the prevalence of
      diabetes mellitus in a representative sample of the adult population, especially
      women, with environmental arsenic exposure after adjustment for seafood intake
      and relevant diabetes risk factors.

PMID- 21723590
TI  - A multi-factor designation method for mapping particulate-pollution control zones
      in China.
AB  - A multi-factor designation method for mapping particulate-pollution control zones
      was brought out through synthetically considering PM(10) pollution status, PM(10)
      anthropogenic emissions, fine particle pollution, long-range transport and
      economic situation. According to this method, China was divided into four
      different particulate-pollution control regions: PM Suspended Control Region,
      PM(10) Pollution Control Region, PM(2.5) Pollution Control Region and PM(10) and
      PM(2.5) Common Control Region, which accounted for 69.55%, 9.66%, 4.67% and
      16.13% of China's territory, respectively. The PM(10) and PM(2.5) Common Control
      Region was mainly distributed in Bohai Region, Yangtze River Delta, Pearl River
      Delta, eastern of Sichuan province and Chongqing municipality, calling for
      immediate control of both PM(10) and PM(2.5). Cost-effective control effects can
      be achieved through concentrating efforts on PM(10) and PM(2.5) Common Control
      Region to address 60.32% of national PM(10) anthropogenic emissions. Air quality
      in districts belonging to PM(2.5) Pollution Control Region suggested that Chinese
      national ambient air quality standard for PM(10) was not strict enough. The
      result derived from application to China proved that this approach was feasible
      for mapping pollution control regions for a country with vast territory,
      complicated pollution characteristics and limited available monitoring data.

PMID- 21723592
TI  - Rheumatoid arthritis recapitulates events relevant in blastocyst implantation and
      embryogenesis: a pathogenetic theory.
AB  - OBJECTIVES: Theoretical considerations support the hypothesis that functionally
      relevant genes were not positively selected for symptomatic chronic inflammatory
      diseases (CIDs) because of 3 major reasons: 1) high negative selection pressure
      with loss of reproducibility; 2) no selection pressure at all (many CIDs of today
      manifest in higher ages, and due to low life expectancy of our ancestors, they
      did not suffer from CIDs that we know today); 3) there was no time for natural
      selection (various CIDs did not exist long enough). Nevertheless, genes can be
      transferred before outbreak of a CID and can confer an increased risk. However,
      these genes were positively selected for fitness in reproduction and survival at
      younger ages independent of a symptomatic CID (antagonistic pleiotropy). Thus,
      relevant genes were conserved for non-life-threatening inflammatory episodes
      (NOLTIES) such as infection or wound healing, which did not impede positive
      selection. Importantly, blastocyst implantation and embryogenesis are NOLTIES. We
      hypothesized that factors relevant in blastocyst implantation and embryogenesis
      are also found in active tissue inflammation of a CID. METHODS: Rheumatoid
      arthritis (RA) was used as a paradigmatic CID. An extensive database search in
      PubMed and OMIM of the U.S. National Library of Medicine was conducted. RESULTS:
      Many important similarities between RA and blastocyst implantation/embryogenesis
      were found including stem cell pathways, hormonal pathways, angiogenesis,
      neuronal pathways, the wingless (Wnt) pathway, the Notch pathway, the TGF-beta
      superfamily, matrix metalloproteinases, and others. CONCLUSIONS: It turned out
      that many factors of RA inflammation were borrowed from the non-life-threatening
      episode of blastocyst implantation and embryogenesis.

PMID- 21723591
TI  - The cross-sectional relationship of hemoglobin levels and functional outcomes in
      women with self-reported osteoarthritis: results from the Women's Health
      Initiative.
AB  - OBJECTIVES: Gastrointestinal blood loss is a recognized complication of the use
      of nonsteroidal anti-inflammatory drugs (NSAIDS) in patients with arthritis. We
      examined the cross-sectional relationship of patient-reported outcomes of overall
      health, physical function, vitality, and quality of life to hemoglobin (hgb)
      levels in postmenopausal women with self-reported osteoarthritis to determine
      whether hgb levels as potential markers of chronic blood loss were associated
      with these functional outcomes. METHODS: Postmenopausal women (N = 64,850) with
      self-reported osteoarthritis (srOA) at baseline in the Women's Health Initiative
      study, excluding participants with chronic or hemolytic diseases associated with
      anemia, had hgb levels measured and completed Short-Form Health Surveys. General
      linear models analysis adjusting for potential confounders was performed.
      RESULTS: A nonlinear plateauing relationship between hgb levels and functional
      outcomes was found. Participants with srOA had statistically significantly worse
      overall health, physical function, and vitality, but not quality of life, for
      each gram of hgb below 14 g/dL, compared with those with hgb 14 g/dL (P < 0.001).
      Participants with srOA taking NSAIDS had worse functional outcomes for each level
      of hgb compared with those not reporting NSAIDS use. CONCLUSIONS: In cross
      sectional analyses of postmenopausal women with srOA, differences in hgb levels
      are related to differences in functional outcomes of overall health, physical
      function, and vitality at clinically important levels. Prospective studies
      evaluating whether changes in hgb levels result in changes in functional outcomes
      in participants with osteoarthritis are needed to confirm of our findings and
      before any changes in therapeutics based on hemoglogin levels are considered in
      the care of patients with osteoarthritis.

PMID- 21723593
TI  - Spleen calcifications in connective tissue disorders.

PMID- 21723594
TI  - Prolapse follow-up at 5 years or more: myth or reality?
AB  - OBJECTIVES: To study the loss to follow-up (LTF) rate in level I/II evidence
      based studies related to the surgical management of pelvic organ prolapse (POP).
      METHODS: Randomized controlled trials (level I) or nonrandomized but prospective
      studies (level II) related to the surgical treatment of POP from January 1995 to
      November 2010 were searched in PubMed. Data reviewed included types of study,
      number of participating centers, sample size calculation, surgical techniques,
      power calculation, estimated dropout rate, duration of follow-up, and rate and
      reasons for LTF. RESULTS: Forty-eight articles (4776 women)--22 randomized
      controlled trials and 26 nonrandomized prospective studies--met the inclusion
      criteria. Twenty-one articles gave details on sample size calculation, and only 5
      explained their LTF rate after reaching LTF patients by mail or telephone.
      Percentages of LTF patients were 9.8% (255/2609) at <=12 months in 26 articles,
      15% (184/1232) at 24 months in 12 articles, 27% (114/420) at 36 months in 8
      articles, 44% (272/615) at 60 months in 4 articles, and 60% (273/456) at >60
      months in 3 articles. Fifteen articles reported no missing data, mostly because
      of small sample size or short follow-up. Only 3 articles defined LTF patients as
      treatment failure or successes and reported outcomes accordingly. CONCLUSIONS: An
      acceptable attrition rate (10-20%) in studies with a 2-3-year follow-up period
      was noted, but a much higher rate in studies extending 3-5 years out. Meaningful
      long-term follow-up reporting at 5 years, as usually recommended after POP
      repair, seems unrealistic.

PMID- 21723595
TI  - Clinical Stage T1 micropapillary urothelial carcinoma presenting with metastasis
      to the pancreas.
AB  - Micropapillary carcinoma of the bladder is an extremely aggressive variant of
      urothelial carcinoma. Radical cystectomy is the standard treatment for all
      patients, including those with nonmuscle-invasive disease. We present a patient
      diagnosed with clinical Stage T1 micropapillary carcinoma of the bladder who was
      found to have a 2-cm metastasis to the head of the pancreas. To our knowledge,
      this case represents the first report of a solitary metastatic urothelial
      carcinoma to the pancreas.

PMID- 21723596
TI  - SCOTCERV: a phase II trial of docetaxel and gemcitabine as second line
      chemotherapy in cervical cancer.
AB  - OBJECTIVE: The aim of the study was to determine the response rate and response
      duration of cervical cancer previously treated by cisplatin (with or without
      radiation) to a combination of docetaxel and gemcitabine. Secondary endpoints
      were assessment of toxicity and quality of life (QoL) of patients receiving the
      treatment. METHODS: This was a multicentre phase II trial of 3 weekly docetaxel
      75 mg/m(2) day 1 (reduced to 60 mg/m(2) after 32 cycles had been administered)
      and gemcitabine 1000 mg/m(2) (days 1 and 8). A two stage Gehan design was used
      initially. Twenty-nine patients recruited had disease outside the irradiated
      pelvis (Group 1), and 21 had disease confined to the irradiated pelvis (Group 2).
      The target response for the Gehan 2 design was 25% (Group 1) and 10% (Group 2).
      RESULTS: The overall response rate for Group 1 was 21.4% (95% CI 8.3-41.0%).
      Amongst those who had at least 3 cycles of chemotherapy the response rate was
      27.3% (95% CI 10.7-50.2%). The median survival was 7.3 months (95% CI 5.4 to 9.2
      months) with 39.3% (95% CI 21.7-56.5%) alive at 1 year. In Group 2 the overall
      response rate was 9.5% (95% CI 1.2%-30.4%). The response rate for those who had
      at least 3 cycles of chemotherapy was 12.5% (95% CI 1.6-38.4%). The median
      survival was 7.9 months (95% CI 2.2-13.6 months). Toxicity was mainly
      haematological with 51% developing grade 3 or 4 neutropenia after at least 1
      cycle of chemotherapy. QoL showed a significant deterioration from baseline for
      physical and role function but there was an improvement in emotional function
      during treatment. CONCLUSION: Response rates and survival duration were similar
      to those reported following treatment with platinum based doublets. In view of
      the relatively poor response rates (no more than 36%) to conventional
      chemotherapy future developments should be a combination of chemotherapy and
      biological agents such as VEGFR inhibitors.

PMID- 21723597
TI  - Sorafenib as a third line therapy in patients with epithelial ovarian cancer or
      primary peritoneal cancer: a phase II study.
AB  - PURPOSE: New agents are required for the patients with epithelial ovarian cancer
      (EOC) who progress after first and second line of the treatment. Tumor
      vasculature targeted agents are potentially active in EOC. We aimed to assess the
      activity of sorafenib in patients with recurrent EOC who had received two prior
      therapies. PATIENTS AND METHODS: A phase II non-randomized, open-label, single
      arm study aimed to assess the efficacy, safety and tolerance of sorafenib
      monotherapy as a third line therapy in patients with EOC or primary peritoneal
      cancer (PPC). Sorafenib was administered as 400 mg twice daily on days 1-28 of
      each 4-week cycle. The primary end point of the study was to demonstrate the
      progression free survival (PFS). RESULTS: Eleven patients were enrolled. The
      median number of cycles was two. Among the 11 patients eligible for efficacy
      analysis, no patients experienced a partial response or complete response or
      stable disease lasting longer than 6 months according to RECIST criteria. Thus,
      the trial stopped at the end of the first stage of study design. The median PFS
      was 2.00 months (95% CI, 1,80-3,90). The median OS was 11.78 months (95% CI, 7.66
      to 15.39). There were no grade 4 toxicities and few grade 3 toxicities.
      CONCLUSION: Sorafenib fails to achieve sufficient objective response or sustained
      disease stabilization as third-line treatment for EOC.

PMID- 21723598
TI  - Dermacentor tick attached to tympanic membrane.

PMID- 21723599
TI  - Engineering articular cartilage with spatially-varying matrix composition and
      mechanical properties from a single stem cell population using a multi-layered
      hydrogel.
AB  - Despite significant advances in stem cell differentiation and tissue engineering,
      directing progenitor cells into three-dimensionally (3D) organized, native-like
      complex structures with spatially-varying mechanical properties and extra
      cellular matrix (ECM) composition has not yet been achieved. The key innovations
      needed to achieve this would involve methods for directing a single stem cell
      population into multiple, spatially distinct phenotypes or lineages within a 3D
      scaffold structure. We have previously shown that specific combinations of
      natural and synthetic biomaterials can direct marrow-derived stem cells (MSC)
      into varying phenotypes of chondrocytes that resemble cells from the superficial,
      transitional, and deep zones of articular cartilage. In this current study, we
      demonstrate that layer-by-layer organization of these specific biomaterial
      compositions creates 3D niches that allow a single MSC population to
      differentiate into zone-specific chondrocytes and organize into a complex tissue
      structure. Our results indicate that a three-layer polyethylene glycol (PEG)
      based hydrogel with chondroitin sulfate (CS) and matrix metalloproteinase
      sensitive peptides (MMP-pep) incorporated into the top layer (superficial zone,
      PEG:CS:MMP-pep), CS incorporated into the middle layer (transitional zone,
      PEG:CS) and hyaluronic acid incorporated in the bottom layer (deep zone, PEG:HA),
      creates native-like articular cartilage with spatially-varying mechanical and
      biochemical properties. Specifically, collagen II levels decreased gradually from
      the superficial to the deep zone, while collagen X and proteoglycan levels
      increased, leading to an increasing gradient of compressive modulus from the
      superficial to the deep zone. We conclude that spatially-varying biomaterial
      compositions within single 3D scaffolds can stimulate efficient regeneration of
      multi-layered complex tissues from a single stem cell population.

PMID- 21723600
TI  - WITHDRAWN: The effect of molecular design on the physical and biological
      properties of complementary self-assembling peptides.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21723601
TI  - Three-dimensional culture of hepatocytes on porcine liver tissue-derived
      extracellular matrix.
AB  - There is currently no optimal system to expand and maintain the function of human
      adult hepatocytes in culture. Recent studies have demonstrated that specific
      tissue-derived extracellular matrix (ECM) can serve as a culture substrate and
      that cells tend to proliferate and differentiate best on ECM derived from their
      tissue of origin. The goal of this study was to investigate whether three
      dimensional (3D) ECM derived from porcine liver can facilitate the growth and
      maintenance of physiological functions of liver cells. Optimized
      decellularization/oxidation procedures removed up to 93% of the cellular
      components from porcine liver tissue and preserved key molecular components in
      the ECM, including collagen-I, -III, and -IV, proteoglycans, glycosaminoglycans,
      fibronectin, elastin, and laminin. When HepG2 cells or human hepatocytes were
      seeded onto ECM discs, uniform multi-layer constructs of both cell types were
      formed. Dynamic culture conditions yielded better cellular infiltration into the
      ECM discs. Human hepatocytes cultured on ECM discs expressed significantly higher
      levels of albumin over a 21-day culture period compared to cells cultured in
      traditional polystyrene cultureware or in a collagen gel "sandwich". The culture
      of hepatocytes on 3D liver-specific ECM resulted in considerably improved cell
      growth and maintained cell function; therefore, this system could potentially be
      used in liver tissue regeneration, drug discovery or toxicology studies.

PMID- 21723602
TI  - Orientation-regulated immobilization of Jagged1 on glass substrates for ex vivo
      proliferation of a bone marrow cell population containing hematopoietic stem
      cells.
AB  - Notch signaling has been recognized as a key pathway to regulate the
      proliferation and differentiation of hematopoietic stem cells (HSC). In this
      study, the orientation-regulated immobilization of a Notch ligand was designed to
      achieve the efficient Notch ligand-receptor recognition for the ex vivo
      proliferation of a bone marrow cell population containing HSC. Protein A was
      chemically conjugated onto aminated glass substrates, followed by immobilizing a
      recombinant chimeric protein of Jagged1 and Fc domain (Jagged1-Fc) through the
      biospecific binding between protein A and Fc domain. Protein A adsorption was
      suppressed for the Jagged1-Fc-immobilized substrates, in contrast to the Jagged1
      Fc-coated ones, indicating the orientation-regulated immobilization of Jagged1-Fc
      for the substrates. Mouse lineage negative cells (Lin(-)) were cultured on the
      Jagged1-Fc-immobilized substrates. Flow cytometric analyses demonstrated that c
      Kit(+), Sca-1(+), Lin(-), and CD34(-) cells of an HSC population was
      significantly proliferated on the Jagged1-Fc-immobilized substrates 6 days after
      culture, whereas no proliferation was observed for the Jagged1-Fc-coated
      substrates in a random manner or Jagged1-Fc-immobilized ones with a Notch
      signaling inhibitor. It is concluded that the orientation-regulated
      immobilization of Jagged1-Fc increased the efficiency of Jagged1 to recognize the
      Notch receptors, resulting in the promoted ex vivo proliferation of the HSC
      population.

PMID- 21723603
TI  - A computational analysis of the insertion of carbon nanotubes into cellular
      membranes.
AB  - Carbon nanotubes have been proposed to serve as nano-vehicles to deliver genetic
      or therapeutic material into the interior of cells because of their capacity to
      cross the cell membrane. A detailed picture of the molecular mode of action of
      such a delivery is, however, difficult to obtain because of the concealing
      effects of the cell membrane. Here we report a systematic computational study of
      membrane insertion of individual carbon nanotubes and carbon nanotube bundles
      using two entirely different and unrelated techniques. First a static scan of the
      environmental free energy is carried out based on a membrane mimicry approach and
      different insertion geometries are assessed. Then the dynamics is investigated
      with a coarse-grained approach that was previously used in the study of the
      integration dynamics of nanoparticles into the bilayer. The results of both
      models point, for unfunctionalized carbon nanotubes, at a preference for the
      horizontal orientation inside the internal hydrophobic layer of the cell
      membrane. Finally, the energetics of the formation of bundles of carbon nanotubes
      is studied. The cellular membrane promotes aggregation of carbon nanotubes in its
      hydrophobic core and modifies the structural stability of the bundles.

PMID- 21723604
TI  - Effects on growth and oxidative stress status of rice plants (Oryza sativa)
      exposed to two extracts of toxin-producing cyanobacteria (Aphanizomenon
      ovalisporum and Microcystis aeruginosa).
AB  - Toxic cyanobacteria are considered emerging world threats, being responsible for
      the degradation of the aquatic ecosystems. Aphanizomenon ovalisporum produces the
      toxin Cylindrospermopsin (CYN) being a concern in fresh water habitats. This work
      aims to increase our knowledge on the effects of this toxic cyanobacterium in
      plants by studying the alterations in growth parameters and oxidative stress
      status of rice (Oriza sativa) exposed to the cyanobacteria cell extracts
      containing CYN. Significant increases in glutathione S-transferase (GST) and
      glutathione peroxidase (GPx) activities were detected in the different
      experiments performed. The roots showed to be more sensitive than leaves
      regarding the enzyme activities. A reduction in the leaf tissue fresh weight was
      observed after 9 days of plant treatment suggesting a major physiological stress.
      The exposure of rice plants to a mixture of A. ovalisporum and Microcystis
      aeruginosa cell extracts containing CYN and microcystins including microcystin
      LR, resulted in a significant increase in the GST and GPx activities, suggesting
      a synergistic effect of both extracts. Together these results point out the
      negative effects of cyanotoxins on plant growth and oxidative status, induced by
      A. ovalisporum cell extracts, raising also concerns in the accumulation of CYN.

PMID- 21723605
TI  - Pharmacokinetic comparison of orally disintegrating and conventional donepezil
      formulations in healthy Korean male subjects: a single-dose, randomized, open
      label, 2-sequence, 2-period crossover study.
AB  - BACKGROUND: Donepezil is a potent inhibitor of acetylcholinesterase, an enzyme
      that is targeted in the treatment of Alzheimer's disease. OBJECTIVE: The purpose
      of this study was to compare the pharmacokinetic characteristics of orally
      disintegrating (test) and conventional (reference) donepezil formulations to
      satisfy the regulatory requirement for marketing. METHODS: A single-center
      randomized, single-dose, open-label, 2-way crossover study with a 21-day washout
      period was conducted in 22 healthy volunteers. Plasma samples for the analysis of
      donepezil were collected up to 240 hours after drug administration. Participants
      received either reference or test drug formulation of 10 mg donepezil in the
      first period and the alternative formulation in the second period. Plasma
      concentrations of donepezil were determined by validated high-performance liquid
      chromatography coupled to tandem mass spectrometry detection. Pharmacokinetic
      parameters, including C(max) and AUC, were determined by noncompartmental
      analysis. ANOVA was carried out using log-transformed C(max) and AUC, and the
      mean ratios and their 90% CIs were calculated. The safety profiles and
      tolerabilities of the 2 formulations were also assessed based on laboratory
      tests, 12-lead ECGs, vital signs, and physical examinations. RESULTS: Of the 22
      participants initially enrolled, 18 healthy Korean participants completed both
      treatment periods. Four subjects did not complete both treatments: 3 subjects
      withdrew consent for personal reasons, and 1 subject experienced adverse events.
      No significant differences in pharmacokinetic parameters between the 2
      formulations were observed. The mean (SD) age, height, and weight of the
      participants were 25.8 (4.1) years, 173.6 (5.7) cm, and 68.9 (7.8) kg,
      respectively. The mean (SD) C(max), AUC(last), and AUC(inf) for the reference
      formulation were 33.26 (6.58) ng/mL, 1521.69 (344.04) ng * h/mL, and 1691.46
      (443.05) ng * h/mL, respectively. Corresponding values for the test formulation
      were 34.23 (6.79) ng/mL, 1554.33 (390.23) ng * h/mL, and 1718.27 (447.03) ng *
      h/mL, respectively. The median T(max) was 2 hours (range, 1-3 hours) for the
      reference and test formulations. The geometric mean ratios (90% CI) between the 2
      formulations of donepezil were 102.9 (96.8-109.5) for C(max), 102.3 (96.1-108.9)
      for AUC(last), and 101.6 (95.4-108.2) for AUC(0-infinity), respectively. During
      the study, 15 and 14 adverse events were reported for the reference and test
      formulations, respectively, and all were transient, mild, and resolved during the
      treatment period. These adverse events included 7 cases of nausea, 3 cases of
      headache, and 1 case each of dizziness, vomiting, chills, and sweating. All
      adverse events were considered related to the study drugs. CONCLUSION: This study
      found that the test and reference formulations met the regulatory criteria for
      pharmacokinetic equivalence in these fasting healthy Korean male subjects. Both
      donepezil formulations appeared to be generally well tolerated.

PMID- 21723606
TI  - Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl
      peptidase-4 inhibitor linagliptin: a 4-week multicenter, randomized, double
      blind, placebo-controlled phase IIa study in Japanese type 2 diabetes patients.
AB  - BACKGROUND: The dipeptidyl-peptidase-4 (DPP-4) inhibitor linagliptin is under
      clinical development for treatment of type 2 diabetes mellitus (T2DM). In
      previous studies in white populations it showed potential as a once-daily oral
      antidiabetic drug. OBJECTIVES: In compliance with regulatory requirements for new
      drugs intended for use in the Japanese population, this study investigated the
      pharmacokinetics, pharmacodynamics, and tolerability of multiple oral doses of
      linagliptin in Japanese patients with T2DM. METHODS: In this randomized, double
      blind, placebo-controlled multiple dose study, 72 Japanese patients with T2DM
      were assigned to receive oral doses of linagliptin 0.5, 2.5, or 10 mg or placebo
      (1:1:1:1 ratio) once daily for 28 days. For analysis of pharmacokinetic
      properties, linagliptin concentrations were determined from plasma and urinary
      samples obtained throughout the treatment phase, with more intensive samplings on
      days 1 and 28. DPP-4 inhibition, glycosylated hemoglobin A1c (HbA(1c)) levels,
      and plasma glucose and glucagon-like peptide-1 (GLP-1) levels were compared by
      mixed effect model. Tolerability was assessed throughout the study by physical
      examination, including blood pressure and pulse rate measurements, 12-lead ECG,
      and laboratory analysis. RESULTS: Baseline demographic characteristics were well
      balanced across the 4 treatment groups (mean [SD] age, 59.7 [6.4] years in the
      placebo group, 60.8 [9.2] years in the 0.5 mg group, 60.2 [6.4] years in the 2.5
      mg group, and 59.1 [8.6] years in the 10 mg group; mean [SD] weight, 67.2 [10.0]
      kg in the placebo group, 64.5 [9.0] kg in the 0.5 mg group, 69.6 [9.4] kg in the
      2.5 mg group, and 63.5 [12.2] kg in the 10 mg group; mean [SD] duration of T2DM
      diagnosis, 5.1 [4.2] years in the placebo group, 5.2 [4.7] years in the 0.5 mg
      group, 5.9 [4.8] years in the 2.5 mg group, and 2.6 [2.3] years in the 10 mg
      group). The majority of the patients treated were male (76.4%). Use of previous
      antidiabetic medication was more common in the 2.5 mg linagliptin group (44%)
      than in the 0.5 or 10 mg linagliptin (15.8% and 22.2%, respectively) or placebo
      groups (35.3%). Total systemic exposure in terms of linagliptin AUC and C(max)
      (which occurred at 1.25-1.5 hours) increased in a less than dose-proportional
      manner. The terminal half-life was long (223-260 hours) but did not reflect the
      accumulation half-life (10.0-38.5 hours), resulting in a moderate accumulation
      ratio of <2.9 that decreased with increasing dose. Urinary excretion increased
      with linagliptin doses but was <7% at steady state for all dose groups.
      Inhibition of plasma DPP-4 at 24 hours after the last dose on day 28 was
      approximately 45.8%, 77.8%, and 89.7% after linagliptin 0.5, 2.5, and 10 mg,
      respectively. At steady state, linagliptin was associated with dose-dependent
      increases in plasma GLP-1 levels, and the postprandial GLP-1 response was
      enhanced. Statistically significant dose-dependent reductions were observed in
      fasting plasma glucose levels at day 29 for all linagliptin groups (-11.5, -13.6,
      and -25.0 mg/dL for the 0.5, 2.5, and 10 mg groups, respectively; P < 0.05 for
      all linagliptin groups). Linagliptin also produced statistically significant dose
      dependent reductions from baseline for glucose area under the effect curve over 3
      hours after meal tolerance tests (-29.0 to -68.1 mg * h/dL; P < 0.05 for all 3
      linagliptin groups). For the 0.5 and 10 mg linagliptin-treated groups, there were
      statistically significant reductions in HbA(1c) from baseline compared with
      placebo, despite the relatively low baseline HbA(1c) (7.2%) and small sample size
      (P < 0.01 for both groups). The greatest reduction in HbA(1c) (-0.44%) was seen
      in the highest linagliptin dose group (10 mg). On dosing for up to 28 days,
      linagliptin was well tolerated with no reported serious adverse events or
      symptoms suggestive of hypoglycemia. Overall, fewer adverse events were reported
      by patients after linagliptin than after placebo (11 of 55 [20%] vs 6 of 17
      [35%]). CONCLUSIONS: Linagliptin demonstrated a nonlinear pharmacokinetic profile
      in these Japanese patients with T2DM consistent with the findings of previous
      studies in healthy Japanese and white patients. Linagliptin treatment resulted in
      statistically significant and clinically relevant reductions in HbA(1c) as soon
      as 4 weeks after starting therapy in these Japanese patients with T2DM,
      suggesting that clinical studies of longer duration in Japanese T2DM patients are
      warranted.

PMID- 21723607
TI  - Multimodality approach in cryptogenic epilepsy with focus on morphometric 3T MRI.
AB  - PURPOSE: This study aimed to investigate the potential contribution of
      morphometric MRI analysis in comparison to other modalities, such as MEG, SPECT
      and PET, in identifying the epileptogenic focus in patients with cryptogenic
      epilepsy. PATIENTS AND METHODS: Study inclusion was limited to epilepsy patients
      with a monolobar focus hypothesis, as concluded from EEG/seizure semiology and
      the best individual concordance rate. Feature maps, generated by the MATLAB((r))
      "morphometric analysis program" (MAP), were evaluated by a neuroradiologist
      blinded to conventional MRI and the focus hypothesis (MAP(1)). In addition, the
      feature maps were also interpreted by simultaneous matching conventional MRI but,
      again, with the reader having no knowledge of the focus hypothesis (MAP(2)).
      RESULTS: In 12 out of 51 patients, true-positive findings were achieved (MAP(1):
      sensitivity 24%; specificity 96%). The sensitivity of the MAP(1) results was
      superior extratemporally. After matching conventional MRI, FCD was traced in six
      of the 12 patients (MAP(2): sensitivity 12%; specificity 100%). MEG sensitivity
      was 62%. Sensitivity of interictal and ictal SPECT was 20% and 50%, respectively.
      PET was not as sensitive extratemporally (19%) as temporally (82%). The greatest
      correspondence with the best individual concordance rate was noted with PET
      (14/16; 88%) and MEG (8/10; 80%), followed by interictal (5/8; 63%) and ictal
      (9/15; 60%) SPECT. Results for MAP(1) were 53% (10/19), and 100% for MAP(2)
      (6/6). CONCLUSION: Although MAP sensitivity and specificity results are lower in
      comparison to other modalities, implementation of the technique should be
      considered first, before arranging any further investigations. The present study
      results offer guidelines for the implementation, interpretation and concordance
      of diagnostic procedures.

PMID- 21723608
TI  - Diffusion tensor imaging of the maturing paediatric cervical spinal cord: from
      the neonate to the young adult.
AB  - OBJECTIVE: Normative apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) metrics of the brain have been published previously. However, no
      larger studies evaluated the normal evolution of ADC/FA metrics of the maturing
      paediatric spinal cord. Goal of this study is to evaluate the age-dependent
      evolution of the ADC/FA values of the developing/maturing normal cervical spinal
      cord (CSC). PATIENTS AND METHODS: Forty-one subjects, aged less than 18 years
      with a negative spinal MRI study and no systemic central nervous disease,
      underwent diffusion tensor imaging (DTI) of the CSC. DTI metrics were measured in
      the centre of the CSC. Regression and ANCOVA analyses were performed to evaluate
      the association between ADC/FA values and age and its potential modification by
      sex. RESULTS: A linear model emerged as the best fit for our data. ADC showed a
      continuous decrease with age; FA showed a continuous increase with age.
      CONCLUSION: The simultaneous age-related ADC decrease and FA increase likely
      reflect progressive maturation, myelination and fibre packing within the CSC
      similar to that observed in the brain. Collection of age-dependent normative DTI
      metrics may be helpful in the early identification and quantification of altered
      water diffusion in a variety of pathologies affecting the developing paediatric
      spinal cord.

PMID- 21723609
TI  - Regional risk assessment for contaminated sites part 1: vulnerability assessment
      by multicriteria decision analysis.
AB  - As highlighted in the EU Soil Communication, local contamination is one of the
      main soil threats and it is often related to present and past industrial
      activities which left a legacy of a high number of contaminated sites in Europe.
      These contaminated sites can be harmful to many different receptors according to
      their sensitivity/susceptibility to contamination, and specific vulnerability
      evaluations are needed in order to manage this widely spread environmental issue.
      In this paper a novel comprehensive vulnerability assessment framework to assess
      regional receptor susceptibility to contaminated site is presented. The developed
      methodology, which combines multi criteria decision analysis (MCDA) techniques
      and spatial analysis, can be applied to different receptors recognized as
      relevant for regional assessment. In order to characterize each receptor, picked
      parameters significant for the estimation of the vulnerability to contaminated
      sites have been selected, normalized and aggregated by means of multi criteria
      decision analysis (MCDA) techniques. The developed MCDA methodology, based on the
      Choquet integral, allows to include expert judgments for the elicitation of
      synergic and conflicting effects between involved criteria and is applied to all
      the geographical objects representing the identified receptors. To test the
      potential of the vulnerability methodology, it has been applied to a specific
      case study area in the upper Silesia region of Poland where it proved to be
      reliable and consistent with the environmental experts' expected results. The
      vulnerability assessment results indicate that groundwater is the most vulnerable
      receptor characterized by a wide area with vulnerability scores belonging to the
      highest vulnerability class. As far as the other receptors are concerned, human
      health and surface water are characterized by quite homogeneous vulnerability
      scores falling in the medium-high vulnerability classes, while protected areas
      resulted to be the less vulnerable receptor with only one protected area falling
      in the medium vulnerability class. The vulnerability assessment results will
      support the regional risk assessment for the ranking of potentially contaminated
      sites at regional scale.

PMID- 21723610
TI  - Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic
      signaling during Herpes simplex virus infection.
AB  - Trichosanthin (TCS) is a type I ribosome-inactivating protein with wide spectrum
      of pharmacological activities. It inhibits human immunodeficiency virus type 1
      (HIV-1) and Herpes simplex virus type 1 (HSV-1) replication but the mechanism is
      not clear. From a previous study, TCS was found to be more cytotoxic to HIV-1
      infected cells than uninfected cells. Similar finding was confirmed with HSV-1 in
      the present study. TCS induced cell death in HEp-2 cells and the EC(50) was
      24.64MUg/mL. When the same experiment was performed in HSV-1 infected HEp-2
      cells, the EC(50) decreased to 3.01MUg/mL. TCS appeared to cause more death and
      apoptosis in viral infected cells. This study explored plausible mechanism with
      respect to the apoptosis signal pathways. In uninfected cells, TCS induced CD95
      (Fas)-mediated and caspase-8-dependent type I apoptosis. When cells were infected
      with HSV-1, apoptosis induced by TCS clearly switched to a more potent type II
      pathway. This involved mitochondrial depolarization and caspase-9 activation. The
      major evidences arose from studying the individual signals of the two apoptosis
      pathways in infected and uninfected cells. In addition, over expression of Bcl-2,
      which mainly affected the type II pathway reduced TCS induced apoptosis mostly in
      infected cells. This further demonstrated that the type II pathway was operating
      in infected cells. The reason for the switching is not entirely clear but it is
      well known that viral infection affects signal pathways especially those related
      to apoptosis. In conclusion, TCS selectively induces more apoptosis in HSV-1
      infected cells than uninfected cells. The consequence of infection switches the
      TCS-induced apoptosis pathway from a CD95 (Fas) dependent type I to a more potent
      type II pathway mediated by mitochondrial depolarization and caspase-9
      activation.

PMID- 21723611
TI  - Lipid rafts hinder binding of antibodies to the extracellular segment of the
      membrane-anchor peptide of mIgA.
AB  - Membrane-bound IgA (mIgA) is associated with Igalpha/Igbeta as the B cell
      receptor (BCR) complex on mIgA-expressing B cells. The alpha chain of mIgA
      (malpha) contains a C-terminal membrane-anchor peptide, which encompasses
      extracellular, transmembrane and intracellular segments. The extracellular
      segment, referred to as the mIg isotype-specific (migis-alpha) segment or the
      extracellular membrane proximal domain of malpha, has been proposed to be a
      specific antigenic site suitable for isotype-specific targeting of mIgA
      expressing B cells by antibodies. In this study, we developed several anti-migis
      alpha monoclonal antibodies (mAbs), such as mAb 29C11, specific to a segment
      towards the N-terminus of the 26 amino acid long migis-alpha. The mAbs bound
      strongly to synthetic peptides of migis-alpha and to various recombinant proteins
      containing migis-alpha as revealed by ELISA. On B cells, however, flow cytometric
      analysis suggested that these mAbs did not bind strongly to mIgA. After lipid
      rafts of B cells were disrupted by cholesterol extraction, the mAbs were able to
      bind strongly to the treated B cells. Moreover, immunoprecipitation analysis of
      these mAbs indicated that mIgA could only be pulled down by the mAbs when mIgA
      expressing B cells were solubilized by strong detergents, such as sodium dodecyl
      sulfate (SDS), or when lipid rafts were disrupted. Together, these results
      suggest that the migis-alpha region of mIgA in the BCR is associated with lipid
      rafts, which hinder binding of migis-alpha-specific antibodies to mIgA on the
      cell surface. Further studies are in progress to evaluate the suitability of
      29C11 or its affinity-improved variants for targeting mIgA-expressing B cells.

PMID- 21723612
TI  - In vitro C3 deposition on Cryptococcus capsule occurs via multiple complement
      activation pathways.
AB  - Complement can be activated via three pathways: classical, alternative, and
      lectin. Cryptococcus gattii and Cryptococcus neoformans are closely related
      fungal pathogens possessing a polysaccharide capsule composed mainly of
      glucuronoxylomannan (GXM), which serves as a site for complement activation and
      deposition of complement components. We determined C3 deposition on Cryptococcus
      spp. by flow cytometry and confocal microscopy after incubation with serum from
      C57BL/6J mice as well as mice deficient in complement components C4, C3, factor
      B, and mannose binding lectin (MBL). C. gattii and C. neoformans activate
      complement in EGTA-treated serum indicating that they can activate the
      alternative pathway. However, complement activation was seen with factor B(-/-)
      serum suggesting activation could also take place in the absence of a functional
      alternative pathway. Furthermore, we uncovered a role for C4 in the alternative
      pathway activation by Cryptococcus spp. We also identified an unexpected and
      complex role for MBL in complement activation by Cryptococcus spp. No complement
      activation occurred in the absence of MBL-A and -C proteins although activation
      took place when the lectin binding activity of MBL was disrupted by calcium
      chelation. In addition, alternative pathway activation by C. neoformans required
      both MBL-A and -C, while either MBL-A or -C was sufficient for alternative
      pathway activation by C. gattii. Thus, complement activation by Cryptococcus spp.
      can take place through multiple pathways and complement activation via the
      alternative pathway requires the presence of C4 and MBL proteins.

PMID- 21723613
TI  - Use of fellow eye data in the calculation of intraocular lens power for the
      second eye.
AB  - PURPOSE: To test the hypothesis that the refractive outcome of the first eye can
      be used to improve the intraocular lens (IOL) power calculation for the second
      eye. DESIGN: Retrospective, consecutive case series in a university clinic
      setting. PARTICIPANTS: One thousand two hundred thirty-five patients who
      underwent sequential bilateral IOL implantation using the same type of IOL for
      both eyes. METHODS: The refractive outcome was analyzed in retrospect and the IOL
      power calculation was reviewed using 3 different methods: (1) the old Sanders
      Retzlaff-Kraff (SRK) II formula, (2) the newer SRK/T formula, and (3) the more
      recent Olsen formula. In a subgroup of 232 eyes, the actual postoperative
      anterior chamber depth (ACD) was measured using the Lenstar LS900 laser biometer
      (Haag-Streit AG, Koeniz, Switzerland). MAIN OUTCOME MEASURES: The error in
      diopters (D) of the predicted refraction in the spectacle plane. RESULTS: The
      correlation coefficients between the prediction errors for the right and left
      eyes were 0.56, 0.38, and 0.27 for the SRK II, SRK/T, and Olsen formula,
      respectively (P<0.001). Based on the observed correlation, the prediction of the
      second eye could be corrected according to the regression formula: Rx(cor) =
      Rx(exp)+beta*Px(err), where Rx(cor) and Rx(exp) are the corrected and the
      uncorrected refractive prediction, respectively, Px(err) is the observed error of
      the first eye, and beta is a formula-specific regression coefficient. Using this
      formula, the mean absolute error (MAE) was found to decrease from 0.56 D to 0.46
      D, from 0.47 D to 0.41 D, and from 0.42 D to 0.40 D with the SRK II (P<0.001),
      the SRK/T (P<0.001), and the Olsen formula (P<0.05), respectively. Substituting
      the measured postoperative ACD of the first eye for the estimated ACD for the
      second eye in the Olsen formula was found to have a similar accuracy as the
      empirical regression formula. CONCLUSIONS: Depending on the IOL power calculation
      formula, the prediction error of the first eye may be used to improve the
      prediction for the second eye. The reason for this effect seems to be the formula
      dependent inaccuracy in the prediction of the IOL position (ACD) after surgery.

PMID- 21723614
TI  - Comparative effectiveness and cost-effectiveness of the implantable miniature
      telescope.
AB  - OBJECTIVE: To assess the preference-based comparative effectiveness (human value
      gain) and the cost-utility (cost-effectiveness) of a telescope prosthesis
      (implantable miniature telescope) for the treatment of end-stage, age-related
      macular degeneration (AMD). DESIGN: A value-based medicine, second-eye model,
      cost-utility analysis was performed to quantify the comparative effectiveness and
      cost-effectiveness of therapy with the telescope prosthesis. PARTICIPANTS:
      Published, evidence-based data from the IMT002 Study Group clinical trial.
      Ophthalmic utilities were obtained from a validated cohort of >1000 patients with
      ocular diseases. METHODS: Comparative effectiveness data were converted from
      visual acuity to utility (value-based) format. The incremental costs (Medicare)
      of therapy versus no therapy were integrated with the value gain conferred by the
      telescope prosthesis to assess its average cost-utility. The incremental value
      gains and incremental costs of therapy referent to (1) a fellow eye cohort and
      (2) a fellow eye cohort of those who underwent intra-study cataract surgery were
      integrated in incremental cost-utility analyses. All value outcomes and costs
      were discounted at a 3% annual rate, as per the Panel on Cost-Effectiveness in
      Health and Medicine. MAIN OUTCOME MEASURES: Comparative effectiveness was
      quantified using the (1) quality-adjusted life-year (QALY) gain and (2) percent
      human value gain (improvement in quality of life). The QALY gain was integrated
      with incremental costs into the cost-utility ratio ($/QALY, or US dollars
      expended per QALY gained). RESULTS: The mean, discounted QALY gain associated
      with use of the telescope prosthesis over 12 years was 0.7577. When the QALY loss
      of 0.0004 attributable to the adverse events was factored into the model, the
      final QALY gain was 0.7573. This resulted in a 12.5% quality of life gain for the
      average patient during the 12 years of the model. The average cost-utility versus
      no therapy for use of the telescope prosthesis was $14389/QALY. The incremental
      cost-utility referent to control fellow eyes was $14063/QALY, whereas the
      incremental cost-utility referent to fellow eyes that underwent intra-study
      cataract surgery was $11805/QALY. CONCLUSIONS: Therapy with the telescope
      prosthesis considerably improves quality of life and at the same time is cost
      effective by conventional standards.

PMID- 21723615
TI  - Seroprevalence of antibodies to pandemic (H1N1) 2009 influenza virus among health
      care workers in two general hospitals after first outbreak in Kobe, Japan.
AB  - OBJECTIVE: To assess the prevalence including asymptomatic infection, infection
      risk of exposure to patients, and effectiveness of personal protective equipment
      (PPE) among health care workers (HCWs) during the first pandemic (H1N1) 2009
      (pH1N1) outbreak in Kobe, Japan in May 2009. METHODS: A cross-sectional
      seroepidemiological study was conducted on 268 HCWs in the two hospitals in Kobe
      to which all pH1N1 inpatients were directed. Participating HCWs completed a self
      administrated questionnaire and provided a single serum sample which was analyzed
      using a hemagglutination-inhibition (HI) antibody test. RESULTS: Of 268 subjects,
      14 (5.2%) were found to have positive antibodies to the pH1N1 by HI assay; only 1
      reported a febrile episode. Among the 14 seropositive cases, 8 received
      chemoprophylaxis. 162 HCWs (60.4%) had been exposed to patients. The seropositive
      rate (SPR) for pH1N1 of the exposed group was higher than that of the unexposed
      group, however not statistically significant (6.8% vs. 3.1%, p = 0.197). There
      were no statistically significant differences in SPR for any PPE. CONCLUSION: The
      SPR for pH1N1 in the exposed group was higher than that of the unexposed group in
      HCWs; however, most of these individuals were asymptomatic. There was no
      statistically significant association between PPE implementation and pH1N1
      seropositivity.

PMID- 21723616
TI  - Impulsivity, aggression and suicidal behavior in unipolar and bipolar disorders.
AB  - BACKGROUND: Predictors of suicidal behaviors (SB) in bipolar (BD) and major
      depressive disorder (MDD) patients are poorly understood. It has been recognized
      that behavioral dysregulation characterizes SB with traits of impulsivity and
      aggression being particularly salient. However, little is known about how these
      traits are segregated among mood disorder patients with and without a history of
      suicide attempt (SA). METHODS: This article aims to compare impulsivity and
      aggression between 143 controls, 138 BD and 186 MDD subjects with or without a
      history of SA. RESULTS: BD and MDD patients showed higher impulsivity scores (BIS
      10 = 57.9 vs. 44.7, p < 0.0001) and more severe lifetime aggression than controls
      (Lifetime History of Aggression = 7.3 vs. 3.9, p < 0.0001). Whereas impulsivity
      helped to distinguish MDD subjects without a history of SA from those with such a
      history, this was not the case in BD subjects where no difference in impulsive
      traits was observed between BD without and with history of SA (57.2 vs. 63.2 for
      BIS-10; p = 0.259). Impulsive and aggressive traits were strongly correlated in
      suicide attempters (independently of the diagnosis) but not in non-suicide
      attempters. LIMITATIONS: Dimensional traits were not characterized at different
      stages of illness. CONCLUSIONS: Impulsivity, as a single trait, may be a reliable
      suicide risk marker in MDD but not in BD patients, and its strong correlation
      with aggressive traits seems specifically related to SB. Our study therefore
      suggests that the specific dimension of impulsive aggression should be
      systematically assessed in mood disorder patients to address properly their
      suicidal risk.

PMID- 21723617
TI  - Coping strategies and psychological morbidity in family carers of people with
      dementia: a systematic review and meta-analysis.
AB  - BACKGROUND: Carers for people with dementia experience high levels of anxiety and
      depression. Coping style has been associated with carer anxiety and depression.
      METHOD: We systematically reviewed studies examining the relationships between
      coping and anxiety or depression among carers of people with dementia. We rated
      study validity using standardised checklists. We calculated weighted mean
      correlations (WMC) for the relationships between coping and psychological
      morbidity, using random effects meta-analyses. RESULTS: We included 35 studies.
      Dysfunctional coping correlated with higher levels of anxiety (WMC=0.39, 95% CI
      0.28-0.50; N=688) and depression (0.46, 0.36-0.56; N=1428) cross-sectionally, and
      with depression 6 and 12months later (0.32, 0.10-0.54; N=143). Emotional support
      and acceptance-based coping correlated with less anxiety (-0.22, 95% CI -0.26 to 
      0.18; N=628) and depression (-0.20, -0.28 to -0.11; N=848) cross-sectionally; and
      predicted anxiety and depression a year later in the only study to measure this.
      Solution-focused coping did not correlate significantly with psychological
      morbidity. LIMITATIONS: Just over a quarter of the identified studies provided
      extractable data for meta-analysis, including only two longitudinal studies.
      CONCLUSIONS: There is good evidence that using more dysfunctional, and less
      emotional support and acceptance-based coping styles are associated with more
      anxiety and depression cross-sectionally, and there is preliminary evidence from
      longitudinal studies that they predict this morbidity. Our findings would support
      the development of psychological interventions for carers that aim to modify
      coping style.

PMID- 21723618
TI  - Validation of simple visual-analogue thermometer screen for mood complications of
      cardiovascular disease: the Emotion Thermometers.
AB  - OBJECTIVE: Conventional scales may help with the identification of depression but
      are generally too lengthy for clinical practice and perform poorly against
      anxiety and distress. We therefore examined the value of a single item NCCN
      Distress Thermometer and an enhanced visual-analogue method (Emotion
      Thermometers, ET) that incorporates four emotion thermometers. METHODS: We
      examined 228 patients with mixed cardiovascular conditions of whom 200 completed
      questionnaires. 64.5% suffered from cardiomyopathy/congestive heart failure, 9.5%
      had coronary artery disease, 4.5% had multiple cardiac diagnoses, 3% suffered
      from hypertension, 2% had rhythm problem, 2% had valve problems and 1.5% were
      diagnosed with atrial fibrillation. We used DSM-IV criteria to define current
      depression, the GAD7 to define current anxiety and the HADS-T to define distress.
      13% had DSM-IV MDD and 19.1% had major or minor depression using DSM-IV (any
      depression). There were also 59 people (29.6%) with clinically significant
      distress and 46 with clinically significant anxiety (23.1%). RESULTS: The optimal
      accuracy for major depression was either the Depression thermometer (DepT) or the
      Help thermometer (HelpT), as both performed well. They had a sensitivity and
      specificity of 73.1%, 89.7% and 84.6%, 85.6%, respectively. The DepT was also
      best for detecting any DSM-IV depression (sensitivity 68.4% and specificity
      93.2%) and HAD-T based distress (sensitivity 79.7% and specificity 82.9%). The
      Anxiety thermometer (AnxT) performed best against the GAD7 (sensitivity 84.8% and
      specificity 83.7%). CONCLUSION: Innovative visual-analogue screening tools for
      mood appear to perform well in cardiovascular settings.

PMID- 21723619
TI  - How reliable is depression screening in alcohol and drug users? A validation of
      brief and ultra-brief questionnaires.
AB  - BACKGROUND: Depression is highly comorbid with alcohol and drug problems,
      resulting in greater impairment, reduced treatment adherence and poor outcomes.
      Little evidence exists to support the use of mental health screening tools in
      routine addiction treatment. This study tested the validity and reliability of
      PHQ-9 and PHQ-2 as depression case finding tools in an outpatient drug treatment
      sample in the United Kingdom. METHODS: A sample of 103 patients took part in
      diagnostic assessments using CIS-R and completed brief screening questionnaires.
      A subgroup of 60 patients completed retests after 4 weeks. Diagnostic results
      were compared to brief measures using receiver operating characteristic (ROC)
      curves. Psychometric properties were also calculated to evaluate the validity and
      reliability of self-completed questionnaires. RESULTS: A PHQ-9 score >= 12 had a
      sensitivity of 81% and specificity of 75% for major depression, also displaying
      good retest reliability (intra-class correlation, 0.78) and internal consistency
      (Cronbach's alpha, 0.84). PHQ-2 had 68% sensitivity and 70% specificity, with
      more modest retest reliability (0.66) and internal consistency (0.64).
      LIMITATIONS: Diagnostic interviews did not consider the temporal sequencing of
      the onset of drug use and mental health problems. CONCLUSIONS: PHQ-9 is a valid
      and reliable depression screening tool for drug and alcohol users. The brevity
      and ease of administration of self-completed questionnaires make them useful
      clinical tools in addiction services commonly encountering a high prevalence of
      depression.

PMID- 21723620
TI  - Alexithymia in healthy young men: a voxel-based morphometric study.
AB  - BACKGROUND: Alexithymia is a personality construct predominately associated with
      an impaired ability to identify and communicate emotions. Functional imaging
      studies showed that an altered function of the anterior cingulate cortex (ACC)
      may be relevant in alexithymia. In this study we investigated if the altered
      functional anatomy is related to structural changes (A) in the whole brain and
      (B) specifically in the ACC by applying a region-of-interest analysis. METHODS:
      33 high- and 31 low-alexithymic right-handed young male subjects (selected by the
      20-item Toronto Alexithymia Scale, TAS-20) were investigated using voxel-based
      morphometry (VBM) on high-resolution 3D magnetic resonance images. The group
      differences were analyzed by applying voxel-wise comparisons using two-sample t
      tests. Moreover regression analyses with regard to the individual TAS-20 sum
      scores were calculated. RESULTS: Neither the subtraction analyses nor the
      correlation analyses revealed significant differences between high- and low
      alexithymic subjects. Thus, according to our results, the null hypothesis of no
      structural difference between the groups could not be rejected. LIMITATIONS: The
      findings cannot be generalized to female subjects. CONCLUSIONS: Our results did
      not reveal morphological differences between high- and low-alexithymic subjects.
      The functional differences known from imaging studies could not be attributed to
      underlying anatomical changes. Thus, the personality trait of alexithymia might
      be associated with fewer morphological abnormalities than previously assumed.

PMID- 21723621
TI  - Immune-endocrine interactions in treated and untreated cats naturally infected
      with FIV.
AB  - Feline immunodeficiency virus (FIV) is a lentivirus that causes a progressive
      disruption of immune function in cats. The neuroendocrine and immune systems
      communicate bidirectionally, mediated by cytokines such as tumour necrosis factor
      alpha (TNF), several interleukins (IL-1, IL-6, IL-10), and through signals
      induced by the ratio of IL-10 to IL-12. FIV can affect both pituitary adrenal and
      thyroid axis function. Twenty FIV-infected cats in similar stages of the disease
      were evaluated for six months. A cross-sectional study in which the twenty cats
      were divided into two groups was performed. Ten were treated with Zidovudine
      (ZDV: 5mg/kg/d, PO, q12h, for six months) and 10 were untreated. Plasma
      concentrations of adrenocorticotropic hormone (ACTH), cortisol, T4, FT4, T3, IL
      10, IL-12 and viral load (VL) were evaluated after six months. ACTH was found in
      significantly lower concentrations (p<0.0001) in the treated group whereas
      cortisol did not show significant differences between the two groups. Both T4 and
      FT4 had high values in untreated individuals (p<0.001) compared with Zidovudine
      treated cats. T3 did not show significant differences between the two groups.
      Both IL-10 and IL-12 were found in significantly higher concentrations in ZDV
      treated cats (p<0.001). By contrast, the IL10/IL-12 ratio values were
      significantly lower in untreated cats. Viral load was significantly lower in the
      treated cats after six months of therapy, compared with values detected pre
      treatment (p<0.002). Untreated cats showed a significant increase of VL (p<0.04)
      compared with the values at the beginning of the study. In treated cats, VL
      showed lower numbers of viral copies than in untreated cats (p<0.01). In summary,
      Zidovudine treatment appeared to contribute to the normalization of both the
      adrenal and thyroid axes. This effect could be attributed to the decrease
      observed in VL, resulting in a change in cytokine patterns.

PMID- 21723622
TI  - FIV diversity: FIV Ple subtype composition may influence disease outcome in
      African lions.
AB  - Feline immunodeficiency virus (FIV) infects domestic cats and at least 20
      additional species of non-domestic felids throughout the world. Strains specific
      to domestic cat (FIV(Fca)) produce AIDS-like disease progression, sequelae and
      pathology providing an informative model for HIV infection in humans. Less is
      known about the immunological and pathological influence of FIV in other felid
      species although multiple distinct strains of FIV circulate in natural
      populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may
      have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes
      of lion FIV (FIV(Ple)) are endemic, whereby 100% of adult lions are infected with
      one or more of these strains. Herein, the relative distribution of these subtypes
      in the population are surveyed and, combined with observed differences in lion
      mortality due to secondary infections based on FIV(Ple) subtypes, the data
      suggest that FIV(Ple) subtypes may have different patterns of pathogenicity and
      transmissibility among wild lion populations.

PMID- 21723624
TI  - Coexistence of osteoporosis (OP) and coronary artery disease (CAD) in the
      elderly: it is not just a by chance event.
AB  - Cardiovascular disease (CVD) and OP are common age-related conditions. In both
      cross-sectional and longitudinal epidemiologic studies, low bone mass has been
      related to increased frequency of CVD. But available data in geriatric population
      is limited. In this study we aimed to seek the possible relationship between CAD
      and low bone mineral density (BMD) in a large number of geriatric patients. A
      total of 2235 patients aged 65 years or more were included in this cross
      sectional study. All patients underwent a complete geriatric assessment and
      evaluated for CAD and cardiovascular risk factors. BMD was measured by dual
      energy X-ray absorptiometry at the lumbar spine (L1-L4) and femoral neck. BMD
      results were classified into three groups; normal (T-score: >=-1.0*S.D.),
      osteopenia (T-score between -1.0 and -2.5*S.D.), and OP (T-score: <=-2.5*S.D.).
      CAD was present in 397 (29.7%) of 1335 patients with OP, in 199 (27.4%) of 726
      patients with osteopenia and in 34 (19.5%) of 174 patients with normal BMD.
      Multivariate regression analysis revealed that presence of OP or osteopenia
      increased the prevalence of CAD as an independent correlate (OR=1.643; 95%
      CI=1.068-2.528, p=0.030). This study highlights the need for careful evaluation
      of elderly patients with low BMD for possible CAD.

PMID- 21723623
TI  - Clarifying lysosomal storage diseases.
AB  - Lysosomal storage diseases (LSDs) are a class of metabolic disorders caused by
      mutations in proteins critical for lysosomal function. Such proteins include
      lysosomal enzymes, lysosomal integral membrane proteins, and proteins involved in
      the post-translational modification and trafficking of lysosomal proteins. There
      are many recognized forms of LSDs and, although individually rare, their combined
      prevalence is estimated to be 1 in 8000 births. Over two-thirds of LSDs involve
      central nervous system (CNS) dysfunction (progressive cognitive and motor
      decline) and these symptoms are often the most debilitating. Although the genetic
      basis for these disorders is clear and the biochemistry of the proteins well
      understood, the cellular mechanisms by which deficiencies in these proteins
      disrupt neuronal viability remain ambiguous. In this review, we provide an
      overview of the widespread cellular perturbations occurring in LSDs, how they
      might be linked and interventions that may specifically or globally correct those
      defects.

PMID- 21723625
TI  - Vitamin B(12) and folic acid levels as therapeutic target in preserving bone
      mineral density (BMD) of older men.
AB  - The knowledge about vitamin B(12) and folic acid levels in preserving bone mass
      in older men is limited. In this retrospective study, we aimed to find out
      whether levels of vitamin B(12) and folic acid are related to BMD in older men.
      Two hundred and sixty-nine older men were included in the study. Forty-two
      (15.6%) of them had osteoporotic, 150 (55.8%) had osteopenic, and 77 (28.6%) had
      normal BMD. Vitamin B(12) and folic acid levels were categorized as indicating
      normal, borderline, or low vitamin statuses. Femur neck densities showed
      statistically significant differences in subjects having low, borderline, and
      normal vitamin B(12), respectively. There were no significant differences between
      the three tertiles of vitamin B(12) in femur total, trochanteric, and
      intertrochanteric densities. After adjustment for age, body mass index (BMI),
      alcohol, smoking, and exercise with analysis of covariance, the difference was
      still statistically significant between two groups for femur neck density
      (p=0.011). No significant difference was observed between the groups of folic
      acid in any femur sites. We found that the normal level of vitamin B(12) in older
      men may be related to a decrease of femur neck bone loss.

PMID- 21723626
TI  - The prognostic impact of glycated hemoglobin in diabetic ST-elevation myocardial
      infarction.

PMID- 21723627
TI  - Anticoagulation in patients with stroke with infective endocarditis.

PMID- 21723628
TI  - Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and heart
      failure outcomes.

PMID- 21723629
TI  - Coronary malformation with multiple fistulae.

PMID- 21723630
TI  - Prolonged beneficial effect of bosentan treatment and 4-year survival rates in
      adult patients with pulmonary arterial hypertension associated with congenital
      heart disease.
AB  - Pulmonary arterial hypertension (PAH) associated with congenital heart disease
      (CHD) due to systemic to pulmonary shunting is associated with a high risk of
      morbidity and mortality. In this study we evaluated 4 years treatment effect of
      bosentan on exercise capacity and quality of life and survival rates in 64 adult
      patients with PAH associated with CHD, including patients with Down syndrome
      (DS). All patients were evaluated at baseline and during follow-up with
      laboratory tests, 6-minute walk test, quality of life questionnaires, and Doppler
      echocardiography. In total, 13 patients (20%) died during 4-years of follow-up; 4
      patients with DS and 9 patients without DS. Mean follow-up of all patients
      treated with bosentan was 3.5 +/- 1.2 year. We analyzed treatment efficacy
      separately within patients without DS (n=34) and patients with DS (n=30). Mean 6
      minute walking distance (6 MWD) in patients without DS significantly increased at
      6 months from 417 +/- 108 to 458 +/- 104 m (+41 m; p=0.002) and significant
      improvement continued to exist during at least 2.5 years of follow-up (p=0.003).
      Moreover, stroke volume increased significantly (p=0.02). In the patients with
      DS, 6-MWD, stroke volume and quality of life remained stable during treatment. In
      this study we demonstrate a prolonged beneficial effect of bosentan treatment on
      exercise capacity, stroke volume and quality of life in patients without DS.
      However the mortality rate of 20% of patients after 4 years of follow-up remains
      high.

PMID- 21723631
TI  - Trends of selected cattle diseases in eastern Zambia between 1988 and 2008.
AB  - Livestock diseases have long been a challenge to livestock production and public
      health in sub-Saharan Africa and Zambia in particular. The Eastern Province of
      Zambia is one area in Zambia that is not spared by this challenge. Among various
      livestock diseases affecting cattle in this region, the most prominent are East
      Coast Fever (ECF) and African Animal Trypanasomiasis (AAT). Since little has been
      published on the epidemiological trends of these diseases in eastern Zambia, a
      retrospective epidemiological study was carried out using reports that were
      submitted to the provincial veterinary office over the past 20 years. This paper
      assists in evaluating the impact of some of these aid programmes. Data was
      analysed using Excel((c)), SPSS((r)), Epi Info((c)), and Epi Map((c)) software.
      Apparent prevalence of AAT in cattle had decreased in the study period from
      estimates as high as 50% in Katete and Petauke district in 1990 and 1992
      respectively to just below 3% (Petauke and Katete) in 2008, thereby, reducing the
      provincial apparent prevalence from 20% in 1992 to just below 3% in 2008. AAT
      apparent prevalence dropped from estimates as high as 17% in Chadiza district and
      6% in Chipata district in 1990 to just below 1% in 2008 thereby reducing the
      provincial mean prevalence of East Coast Fever from 6% (1990) to 1% (2008). The
      inclusion of donor assistance in disease control programmes for both AAT and ECF
      appeared to have a significant impact on the prevalence of both diseases.

PMID- 21723632
TI  - A cost-benefit analysis of cataract surgery based on the English Longitudinal
      Survey of Ageing.
AB  - This paper uses the English Longitudinal Survey of Ageing to explore the self
      reported effect of cataract operations on eye-sight. A non-parametric analysis
      shows clearly that most cataract patients report improved eye-sight after surgery
      and a parametric analysis provides further information: it shows that the
      beneficial effect is larger the worse was self-reported eye-sight preceding
      surgery so that those with very good or excellent eye-sight do not derive
      immediate benefit. Nevertheless, the long-run effect is suggested to be
      beneficial. Calibrating the results to existing studies of the effect of
      imperfect eye-sight on quality of life, the impact of cataract operations on
      Quality Adjusted Life Years is found to be similar to that established in
      previous studies and well above the costs of cataract operations in most
      circumstances.

PMID- 21723633
TI  - Function of erbB receptors and DNA-PKcs on phosphorylation of cytoplasmic and
      nuclear Akt at S473 induced by erbB1 ligand and ionizing radiation.
AB  - BACKGROUND AND PURPOSE: In the present study effect of erbB2 as well as DNA-PKcs
      on ionizing radiation (IR)- and erbB1 ligand-induced phosphorylation of Akt at
      S473 in cytoplasmic and nuclear fractions was investigated. MATERIALS AND
      METHODS: DNA-PKcs proficient and deficient syngeneic colon carcinoma sublines of
      HCT116 and the glioblastoma cell lines MO59K and MO59J as well as the lung
      carcinoma cell line A549 were used. Akt-S473 phosphorylation was investigated in
      cells pre-treated with pharmacological inhibitors or transfected with siRNA by
      immunoprecipitation, Western blotting and confocal microscopy after different
      stimuli, i.e., ligands and IR. RESULTS: IR-induced phosphorylation of Akt in both
      MO59K and MO59J cell lines but not in HCT116 cells was DNA-PKcs dependent. In
      A549 cells, IR-induced phosphorylation of nuclear Akt-S473 was dependent on
      erbB1, erbB2, and DNA-PKcs. EGF induced phosphorylation of nuclear Akt-S473 in a
      DNA-PKcs and erbB2 independent manner. CONCLUSION: Data indicate that the
      function of DNA-PKcs on IR-induced Akt-S473 phosphorylation is cell line
      specific. IR-induced, but not EGF-induced phosphorylation of cytoplasmic and/or
      nuclear Akt-S473 is erbB2 dependent.

PMID- 21723634
TI  - Accessing radiation response using hypoxia PET imaging and oxygen sensitive
      electrodes: a preclinical study.
AB  - PURPOSE: Tumor hypoxia is a known cause of resistance to radiotherapy. The aim of
      this study was to investigate the prognostic value of hypoxia measured by (18)F
      fluoroazomycin arabinoside ((18)F-FAZA) PET or the Eppendorf oxygen electrode in
      a pre-clinical tumor model. MATERIAL/METHODS: Pretreatment (18)F-FAZA PET scans
      and blood sampling was conducted in 92 Female CDF1 mice with subcutaneous C3H
      mammary carcinomas grown in the right foot. Similarly, oxygenation status of 80
      equivalent tumors was assessed using an invasive oxygen sensitive electrode.
      Tumors were then irradiated with a single dose of 55 Gy and local tumor control
      up to 90 days after the treatment was determined. RESULTS: A significant
      difference in local tumor control between "more hypoxic" or "less hypoxic" groups
      separated either by a median (18)F-FAZA PET determined tumor-to-blood ratio
      (P=0.007; hazard ratio, HR=0.21 [95% CI: 0.06-0.74]), or the fraction of oxygen
      partial pressure (pO(2)) values <=2.5 mmHg (P=0.018; HR=0.31 [95% CI: 0.11
      0.87]), was found. Both assays showed that the more hypoxic tumors had
      significantly lower tumor control. CONCLUSION: (18)F-FAZA PET analysis showed
      that pre treatment tumor hypoxia was prognostic of radiation response. Similar
      results were obtained when oxygenation status was assessed by the Eppendorf pO(2)
      Histograph. The results of this study support the role of (18)F-FAZA as a non
      invasive prognostic marker for tumor hypoxia.

PMID- 21723635
TI  - Molecular and translational radiation biology/oncology: what's up?

PMID- 21723636
TI  - Poorer outcome in Polynesian patients with prostate cancer treated with
      definitive conformational radiation therapy.
AB  - PURPOSE: To compare freedom from biochemical failure (FFBF) of French Polynesian
      (FP) and Native European (NE) prostate cancer patients after definitive conformal
      radiotherapy (RT). PATIENTS AND METHODS: Data were reviewed from medical records
      of 152 consecutive patients (46 FP and 106 NE) with clinically localised prostate
      cancer treated with definitive RT. Neoadjuvant androgen deprivation therapy (ADT)
      was used in 22% of cases. Definition for biochemical failure was a rise by 2
      ng/mL or more above the nadir prostate-specific antigen (PSA) level. The median
      follow-up was 34 months. RESULTS: In comparison to NE patients, FP patients were
      younger (p=0.002) with a higher low-risk proportion (p=0.06). Probability of 5
      year FFBF was 77% in the NE cohort and 58.0% in the FP cohort (p=0.017).
      Univariate analysis showed that FP ethnicity was associated with worse prognosis
      in high-risk tumours (p=0.004). Cox multivariate analysis showed that factors
      associated with FFBF were risk category (p<0.017), and FP origin (p=0.03),
      independently of ADT and radiation dose. CONCLUSION: FP ethnicity was an
      independent prognostic factor for biochemical relapse after definitive conformal
      RT for prostate cancer.

PMID- 21723637
TI  - Bowel exposure in rectal cancer IMRT using prone, supine, or a belly board.
AB  - PURPOSE: To investigate bowel exposure using prone, supine, or two different
      belly boards for rectal cancer intensity modulated RT plans using a full bladder
      protocol. METHODS AND MATERIALS: For 11 volunteers four MR scans were acquired,
      on a flat table in prone, supine, and on two different belly boards (IT-V
      Medizintechnik GmbH(r) (BB1) and CIVCO(r) (BB2)), using a full bladder protocol.
      On each scan a 25*2 Gy IMRT plan was calculated. RESULTS: BB2 led to an average
      bowel area volume reduction of 20-30% at any dose level compared to prone. BB1
      showed a smaller dose reduction effect, while no differences between prone and
      supine were found. Differences between BB2 and prone, supine or BB1 were
      significant up to a level of respectively, 45, 35, and 30 Gy. The reducing effect
      varied among individuals, except for the 50 Gy region, where no effect was found.
      An increase in bladder volume of 100 cc led to a significant bowel area V15
      reduction of 16% independent of scan type. CONCLUSIONS: In the low and
      intermediate dose region a belly board still attributes to a significant bowel
      dose reduction when using IMRT and a full bladder protocol. A larger bladder
      volume resulted in a significant decreased bowel area dose.

PMID- 21723638
TI  - Concurrent high-dose radiotherapy with low-dose chemotherapy in patients with non
      small cell lung cancer of the superior sulcus.
AB  - BACKGROUND AND PURPOSE: In the treatment of patients with tumours of the sulcus
      superior (SST), achieving local control is essential because residual or
      recurrent disease is associated with severe locoregional problems. This study
      evaluates the efficacy of concurrent daily low-dose cisplatin (6 mg/m(2)) and
      high-dose radiotherapy (66 Gy) followed by surgical resection in selected
      patients. MATERIAL AND METHODS: Clinical charts, imaging and pathology reports
      were retrospectively reviewed. Survival was analysed using the Kaplan-Meier
      method. RESULTS: Forty-nine patients with stage II/III SST were treated with
      concurrent high-dose radiotherapy and low-dose chemotherapy (CRT). Mean follow-up
      was 49 months (range 2-152). Nineteen patients underwent additional resection
      after CRT. In 53% a pathological complete response (pCR) was observed (10/19
      pts). Acute severe toxicity occurred in 49% (9/19 pts). Late severe toxicity
      occurred in 3 patients. The 2- and 5-year overall survival was 74% and 33%,
      respectively. Local tumour control was 100%. Thirty patients received CRT only.
      Acute severe toxicity occurred in 23% (7/30 pts). Treatment-related mortality was
      2%. The 2- and 5-year overall survival was 31% and 18%, respectively.
      Locoregional disease-free survival was 48% at 5 years. CONCLUSIONS: Concurrent
      high-dose (66 Gy) radiotherapy and daily low-dose cisplatin was associated with a
      high pCR rate. Excellent local control was achieved after additional resection in
      selected patients. However, the occurrence of severe toxicity in long-term
      survivors after concurrent chemoradiation followed by surgery must be considered.

PMID- 21723639
TI  - The effect of dividing attention between walking and auxiliary tasks in people
      with Parkinson's disease.
AB  - This controlled study examined the effects of dividing attention between walking
      and the performance of a secondary cognitive task in people with mild to moderate
      Parkinson's disease (Hoehn and Yahr stages 2-3.5). Participants in the training
      group (n=6) received 30 min divided attention training in taking big steps while
      simultaneously performing serial three subtractions. Participants in the control
      group (n=6) received no training. Stride length, gait velocity and accurate
      enumeration rate were measured at baseline, immediate after training and 30 min
      after training under single-task (walk only or subtract only) and dual-task (walk
      and subtract) conditions. Data were also collected at training in the training
      group. Immediate improvement in stride length and gait velocity was found when
      instruction was given to participants to pay equal attention to gait and
      subtractions (p=0.001, p=0.05) compared to baseline. Short-term improvement in
      the gait variables was also found after training when compared to the controls
      (p=0.001, p=0.001). Nevertheless, there was no significant difference in the
      accurate enumeration rate. Based on the findings, we conclude that divided
      attention can be used as a strategy to improve slow and short-stepped gait under
      dual-task conditions. Divided attention can also be used in gait training for
      short term stride length and gait velocity improvement.

PMID- 21723640
TI  - Phylogenetic characterization and ochratoxin A--fumonisin profile of black
      Aspergillus isolated from grapes in Argentina.
AB  - Aspergillus section Nigri populations isolated from seven growing regions from
      Argentina were characterized by sequencing in order to identify species
      responsible for production of ochratoxin A (OTA) and fumonisins (FB(s)).
      Sequences of genes encoding calmodulin, beta-tubulin, the second largest subunit
      of RNA polymerase II and translation elongation factor 1 alpha were analysed. The
      phylogenetic analysis showed the presence of six lineages: A. carbonarius, A.
      tubingensis, A. niger, A. japonicus, A. homomorphus and A. foetidus grouped in
      four major clusters. The molecular tools used allowed the identification for the
      first time of A. homomorphus from vineyards. OTA production confirmed the
      importance of A. carbonarius as the main ochratoxigenic species isolated and, to
      a variable degree, of A. niger and A. tubingensis, which were by far the most
      commonly occurring species on grapes in Argentina. The only strains able to
      produce OTA and fumonisins (B(2)-B(4)) belong to the A. niger cluster.

PMID- 21723641
TI  - Scorecards for health system performance assessment: the New Zealand example.
AB  - OBJECTIVE: To develop a national scorecard for assessing health system
      performance derived from routine data. METHODS: We drew upon national and
      international data to develop benchmarks for health system performance, then
      applied basic ratio scores to compare New Zealand performances to the benchmark.
      64 indicators were included in four assessment categories: healthy lives,
      quality, access, and efficiency. In a fifth category, 27 of these indicators were
      used to score health system equity. Indicator scores in each category were then
      averaged to give a health system score out of 100. RESULTS: New Zealand's health
      system achieved an overall score of 71 out of 100. The system scored relatively
      well on quality and efficiency, but poorly on equity despite considerable
      government investment in reducing inequalities. CONCLUSIONS: The scorecard offers
      a useful method for combining a range of data to give an overall picture of
      health system performance, highlighting strengths, weaknesses and areas for
      improvement. This initial study provides a baseline for assessing New Zealand's
      performance over time and, where data permit, a template for other countries to
      follow.

PMID- 21723642
TI  - B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by
      Porphyromonas gingivalis.
AB  - The up-regulation of the B7-H1 receptors in host cells might influence the
      chronicity of inflammatory disorders that frequently precede the development of
      human cancers. B7-H1 expression has been detected in the majority of human
      cancers, leading to anergy and apoptosis of activated T cells, and enabling tumor
      cells to overcome host response. Porphyromonas gingivalis (P. gingivalis), a
      putative periodontal pathogen, is an etiologic agent of periodontitis and
      expresses a variety of virulence factors. In this study, the expression of B7-H1
      and B7-DC receptors on squamous cell carcinoma cells SCC-25 and BHY and primary
      human gingival keratinocytes (PHGK) was analyzed after infection with two
      virulent P. gingivalis strains in vitro. After 48h, the cells were stained with
      antibodies for human B7-H1 and B7-DC and further analyzed by flow cytometry. RNA
      was extracted and gene expression of B7-H1 or B7-DC was quantified by real time
      PCR. After infection with P. gingivalis, both B7-H1 and B7-DC receptors were up
      regulated. The mean fluorescence intensity (MFI) increased from 4.5 to 9.9 (B7
      H1) and from 6.9 to 15.0 (B7-DC) (p<0.05, respectively) in SCC-25 cells. PHGK
      showed an increase from 4.8 to 12.4 (B7-H1) and from 5.5 to 15.6 (B7-DC) (p<0.05,
      respectively). Streptococcus salivarius K12, a commensal bacterium, caused no up
      regulation. After 24h, the expression of B7H1 and B7-DC mRNA in infected cells,
      normalized to GAPDH and in relation to non-infected cells, was 6.4 fold (B7-H1)
      and 8.6 fold (B7-DC) higher. In PHGK B7-H1/DC mRNA expression increased 8.2 fold
      (B7-H1) and 5.9 fold (B7DC) (p<0.05) respectively. The results of the study
      demonstrate that in contrast to S. salivarius K12 virulent P. gingivalis strains
      are able to induce the expression of the B7-H1 and B7-DC receptors in squamous
      carcinoma cells and human gingival keratinocytes, which might facilitate immune
      evasion by oral cancers.

PMID- 21723643
TI  - Nosocomial rotavirus gastroenteritis in a Canadian paediatric hospital:
      incidence, disease burden and patients affected.
AB  - Rotavirus is a well-recognised nosocomial pathogen in paediatric settings.
      Although rotavirus gastroenteritis is a vaccine-preventable disease, there is
      currently no publicly funded programme in Canada. The objective of this study was
      to inform rotavirus vaccination strategy by determining the incidence of
      nosocomial rotavirus gastroenteritis (NRVGE), estimating the burden of disease
      and characterising the patients affected. We performed a retrospective cohort
      study of all NRVGE cases over a period of 10 years in a Canadian tertiary-care
      paediatric hospital. Cases (N = 214) were identified by the hospital's
      prospective surveillance programme for nosocomial infections. The incidence was
      0.5 per 1,000 patient-days (95% confidence interval: 0.43-0.57) with no
      significant decline over the 10-year period. The infection rate per hospital day
      was highest among patients with a hospital stay of > 5 days. A chronic underlying
      medical condition was present in 126 patients (59%), was often associated with
      previous hospitalisation, and was identifiable early in life for 95 patients
      (44%). Rehydration was required for 132 (62%) patients and was intravenous in 98
      (46%). Twenty-six patients (12%) required readmission, for a median of four days,
      for NRVGE that occurred after discharge. Nosocomial rotavirus infection continues
      to be an important problem in paediatric hospitals, predominantly for children
      with underlying medical conditions requiring recurrent and prolonged
      hospitalisation. A rotavirus immunisation programme targeted at vulnerable
      patients, such as infants with congenital pathology and low birth weight,
      requires assessment in Canada and other countries that have not introduced
      universal rotavirus immunisation.

PMID- 21723644
TI  - Cochlea and other spiral forms in nature and art.
AB  - BACKGROUND: The original appearance of the cochlea and the specific shape of a
      spiral are interesting for both the scientists and artists. Yet, a correlation
      between the cochlea and the spiral forms in nature and art has been very rarely
      mentioned. AIM: The aim of this study was to investigate the possible correlation
      between the cochlea and the other spiral objects in nature, as well as the
      artistic presentation of the spiral forms. METHODS: We explored data related to
      many natural objects and examined 13,625 artworks created by 2049 artists. We
      also dissected 2 human cochleas and prepared histologic slices of a rat cochlea.
      RESULTS: The cochlea is a spiral, cone-shaped osseous structure that resembles
      certain other spiral forms in nature. It was noticed that parts of some plants
      are arranged in a spiral manner, often according to Fibonacci numbers. Certain
      animals, their parts, or their products also represent various types of spirals.
      Many of them, including the cochlea, belong to the logarithmic type. Nature
      created spiral forms in the living world to pack a larger number of structures in
      a limited space and also to improve their function. Because the cochlea and other
      spiral forms have a certain aesthetic value, many artists presented them in their
      works of art. CONCLUSIONS: There is a mathematical and geometric correlation
      between the cochlea and natural spiral objects, and the same functional reason
      for their formation. The artists' imagery added a new aspect to those domains.
      Obviously, the creativity of nature and Homo sapiens has no limits--like the
      infinite distal part of the spiral.

PMID- 21723645
TI  - [The challenge of caring for elderly patients more efficiently: an obligation in
      times of crisis].

PMID- 21723646
TI  - Leonurine-cysteine analog conjugates as a new class of multifunctional anti
      myocardial ischemia agent.
AB  - The design, synthesis and biological evaluation of novel Leonurine-cysteine
      analog conjugates 3,5-dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)
      benzoic acid 4-guanidino-butyl ester (1a), 3,5-dimethoxy-4-(2-animo-3
      allysulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (1b) and 3,5
      dimethoxy-4-(3-(2-chlorocarbonyl-ethyldisulfanyl)-propionyl)-benzoic acid 4
      guanidino-butyl ester (2) were reported in this paper. We tested their effects on
      hypoxia-induced neonatal rat ventricular myocytes. Our data showed that all of
      them had cardioprotective effects. Both of 1a and 1b were able to modulate
      hydrogen sulfide production, and 1a possessed higher biological activity than 1b
      and 2, which indicated that there was positive correlation between conjugates and
      their precursors. Furthermore we illuminated that the cardioprotective mechanism
      of 1a were related to increase SOD and CAT activity, decrease MDA and ROS level,
      protect some cell organs and regulate apoptosis-associated genes and proteins
      expression (bcl-2 and bax) via the caspase-3 pathway in molecular level. These
      results indicated that 1a had the potential to be a new class of multifunctional
      anti-myocardial ischemia agent. Most importantly, these results provided us
      important clues for the further design and modification of this type of Leonurine
      cysteine analog conjugates in future.

PMID- 21723647
TI  - New azole antifungal agents with novel modes of action: synthesis and biological
      studies of new tridentate ligands based on pyrazole and triazole.
AB  - The synthesis and extensive biological study of two new tridentates ligands based
      on pyrazole and triazole are described. The antifungal activity against the
      budding yeast cells of the newly synthesized compounds was determined. These
      compounds were toxic to yeast cells. Cell cycle analysis suggested that treatment
      with these compounds impairs cell division in G1 of the cell cycle. Using yeast
      based functional genomics technologies, we found that these compounds tolerance
      requires DNA repair pathway and SKI complex function. We have also found that the
      PKC1 heterozygous deletion strain was the most sensitive to these compounds using
      HaploInsufficiency Profiling, suggesting that the Pkc1 protein may be the target
      for these compounds. These results strongly suggest that these compounds induce
      DNA damage and thus exert a different mechanism of action compared to other azole
      derivatives. These two compounds might therefore represent promising lead
      compounds for further development of antifungal drugs for human therapy.

PMID- 21723648
TI  - Docking and 3D-QSAR (quantitative structure activity relationship) studies of
      flavones, the potent inhibitors of p-glycoprotein targeting the nucleotide
      binding domain.
AB  - In order to explore the interactions between flavones and P-gp, in silico
      methodologies such as docking and 3D-QSAR were performed. CoMFA and CoMSIA
      analyses were done using ligand based and receptor guided alignment schemes.
      Validation statistics include leave-one-out cross-validated R(2) (q(2)), internal
      prediction parameter by progressive scrambling (Q(*2)), external prediction with
      test set. They show that models derived from this study are quite robust. Ligand
      based CoMFA (q(2) = 0.747, Q(*2) = 0.639, r(pred)(2)=0.802) and CoMSIA model
      (q(2) = 0.810, Q(*2) = 0.676, r(pred)(2)=0.785) were developed using atom by atom
      matching. Receptor guided CoMFA (q(2) = 0.712, Q(*2) = 0.497, r(pred)(2) = 0.841)
      and for CoMSIA (q(2) = 0.805, Q(*2) = 0.589, r(pred)(2) = 0.937) models were
      developed by docking of highly active flavone into the proposed NBD (nucleotide
      binding domain) of P-gp. The 3D-QSAR models generated here predicted that
      hydrophobic and steric parameters are important for activity toward P-gp. Our
      studies indicate the important amino acid in NBD crucial for binding in
      accordance with the previous results. This site forms a hydrophobic site. Since
      flavonoids have potential without toxicity, we propose to inspect this
      hydrophobic site including Asn1043 and Asp1049 should be considered for future
      inhibitor design.

PMID- 21723649
TI  - Synthesis and antitubercular evaluation of novel dibenzo[b,d]furan and 9-methyl
      9H-carbazole derived hexahydro-2H-pyrano[3,2-c]quinolines via Povarov reaction.
AB  - A series of novel hexahydro-2H-pyrano[3,2-c]quinoline analogues derived from
      dibenzo[b,d]furan and 9-methyl-9H-carbazole has been synthesized in very good
      yields through SnCl(2).2H(2)O catalyzed one-pot Povarov reaction (imino-Diels
      Alder reaction). The imines generated in situ from dibenzo[b,d]furan-2
      carbaldehyde or 9-methyl-9H-carbazole-3-carbaldehyde and aromatic amines, were
      reacted with 3,4-dihydro-2H-pyran in a diasteroselective manner in acetonitrile
      at RT. These synthesized isomeric pyranoquinoline analogues have been evaluated
      for their in vitro antimycobacterial activity against Mycobacterium tuberculosis
      H37Rv (MTB) by agar dilution method. Among the 23 compounds screened, 5
      (dibenzo[b,d]furan-2-yl)-9-fluoro-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2
      c]quinoline 4f, 5-(dibenzo[b,d]furan-2-yl)-9-fluoro-3,4,4a,5,6,10b-hexahydro-2H
      pyrano[3,2-c]quinoline 5f and 9-fluoro-5-(9-methyl-9H-carbazol-3-yl)
      3,4,4a,5,6,10b-hexa hydro-2H-pyrano[3,2-c]quinoline 7f (MIC 3.13 MUg/mL) were
      resulted as most active antitubercular agents.

PMID- 21723650
TI  - Long term nutritional status and quality of life following major upper
      gastrointestinal surgery - a cross-sectional study.
AB  - BACKGROUND & AIMS: Major upper gastrointestinal surgery results in permanent
      alterations to the gastrointestinal tract, and previously been shown to impair
      nutritional status. The aim of this study was to assess long term nutritional
      status and quality of life in people having had major upper gastrointestinal
      surgery, and the relationship between the two measures. METHODS: People having
      had major upper gastrointestinal surgery greater than 6 months ago were
      recruited. Nutrition assessment included weight, anthropometry, Subjective Global
      Assessment, dietary intake and assessment of gastrointestinal symptoms; quality
      of life was assessed using the EORTC QLQ-C30 questionnaire. Associations between
      nutritional status, type of surgery and quality of life were analysed. RESULTS:
      Thirty people were recruited with fourteen people showing a degree of
      malnutrition according to subjective global assessment. Total gastrectomy and
      oesophagectomy surgery resulted in significantly higher percent weight loss than
      those having undergone pancreaticoduodenectomy (p = 0.01). Subjective global
      assessment correlated with quality of life (p = 0.003). Subjective global
      assessment and gastrointestinal symptoms were both significant variables in
      explaining quality of life (p < 0.001). CONCLUSIONS: Nutritional status in this
      group was significantly compromised, and impacted on quality of life.
      Individualised nutrition intervention to address malnutrition and
      gastrointestinal symptoms should be integrated into post surgery management.

PMID- 21723651
TI  - Driving advice for patients with double vision following zygomatico-orbital
      complex fractures.

PMID- 21723652
TI  - Terrestrial exposure of oilfield flowline additives diminish soil structural
      stability and remediative microbial function.
AB  - Onshore oil production pipelines are major installations in the petroleum
      industry, stretching many thousands of kilometres worldwide which also contain
      flowline additives. The current study focuses on the effect of the flowline
      additives on soil physico-chemical and biological properties and quantified the
      impact using resilience and resistance indices. Our findings are the first to
      highlight deleterious effect of flowline additives by altering some fundamental
      soil properties, including a complete loss of structural integrity of the
      impacted soil and a reduced capacity to degrade hydrocarbons mainly due to: (i)
      phosphonate salts (in scale inhibitor) prevented accumulation of scale in
      pipelines but also disrupted soil physical structure; (ii) glutaraldehyde (in
      biocides) which repressed microbial activity in the pipeline and reduced
      hydrocarbon degradation in soil upon environmental exposure; (iii) the
      combinatory effects of these two chemicals synergistically caused severe soil
      structural collapse and disruption of microbial degradation of petroleum
      hydrocarbons.

PMID- 21723653
TI  - Human trafficking and health: a conceptual model to inform policy, intervention
      and research.
AB  - Human trafficking is an international crime renowned for extreme forms of
      violence against women, men and children. Although trafficking-related violence
      has been well-documented, the health of trafficked persons has been a largely
      neglected topic. For people who are trafficked, health risks and consequences may
      begin before they are recruited into the trafficking process, continue throughout
      the period of exploitation and persist even after individuals are released.
      Policy-making, service provision and research often focus narrowly on criminal
      violations that occur during the period of exploitation, regularly overlooking
      the health implications of trafficking. Similarly, the public health sector has
      not yet incorporated human trafficking as a health concern. We present a
      conceptual model that highlights the migratory and exploitative nature of a multi
      staged trafficking process, which includes: 'recruitment', travel-transit',
      'exploitation' and 'integration' or 'reintegration', and for some trafficked
      persons, 'detention' and 're-trafficking' stages. Trafficked persons may suffer
      from physical, sexual and psychological harm, occupational hazards, legal
      restrictions and difficulties associated with being marginalised or stigmatised.
      Researchers and decision-makers will benefit from a theoretical approach that
      conceptualizes trafficking and health as a multi-staged process of cumulative
      harm. To address a health risk such as trafficking, which spans geographical
      boundaries and involves multiple sectors, including immigration and law
      enforcement, labour, social and health services, interventions must be
      coordinated between nations and across sectors to promote the protection and
      recovery of people who are trafficked.

PMID- 21723654
TI  - Ameloblastoma of the jaws: a retrospective analysis of 340 cases in a Malaysian
      population.
AB  - PURPOSE: Ameloblastoma of the human jaw is an uncommon but clinically significant
      odontogenic epithelial neoplasm. The aim was to analyze the clinicopathologic
      characteristics of ameloblastoma in a Malaysian population. MATERIALS AND
      METHODS: This is a retrospective study (1993 through 2008) of consecutive
      ameloblastoma cases accessioned in 2 main oral pathology diagnostic centers: the
      Unit of Stomatology, Institute for Medical Research and the Department of Oral
      Pathology, Oral Medicine, and Periodontology, Faculty of Dentistry, University of
      Malaya, Kuala Lumpur, Malaysia. Data on patient demographics, tumor location,
      symptomology, duration, radiographic appearance, preoperative diagnosis,
      clinicopathologic subtypes, treatment, and recurrence were analyzed. RESULTS:
      Three hundred forty cases of ameloblastoma were reviewed. These were from 197
      male patients (57.9%) and 143 female patients (42.1%), with a male-to-female
      ratio of 1.4:1. A wide age range (7 to 85 years), mean onset age of 30.3 +/- 16.3
      years, and peak incidence in the second decade of life were recorded. Most were
      mandibular tumors (n = 311/340, 91.5%). These consisted of 95 (28%) unicystic
      ameloblastomas, 221 (65%) solid/multicystic ameloblastomas, 22 (6.4%)
      desmoplastic ameloblastoma, and 2 (0.6%) peripheral ameloblastomas. Unicystic
      ameloblastoma (41.1%) and solid/multicystic ameloblastoma (52.0%) mostly affected
      Malays patients, whereas desmoplastic ameloblastoma (59.1%) was prevalent in
      Chinese patients. Unicystic ameloblastoma (56.8%) and solid/multicystic
      ameloblastoma (47.1%) occurred predominantly in the body and posterior mandible,
      whereas desmoplastic ameloblastoma (36.4%) preferentially involved the anterior
      jaw segment. Most tumors presented as multilocular radiolucencies (36.8%).
      Enucleation (n = 42/92, 45.7%) was the treatment of choice. About 18 cases
      (13.3%) presented with recurrence. CONCLUSIONS: Because ameloblastoma subsets
      differ in their biologic behavior, the present data are significant as baseline
      references for clinicians and pathologists.

PMID- 21723655
TI  - [Evolution and scientific impact of research grants from the spanish society of
      cardiology and spanish heart foundation (2000-2006)].
AB  - INTRODUCTION AND OBJECTIVES: The Sociedad Espanola de Cardiologia (Spanish
      Society of Cardiology) every year awards grants to finance research in the field
      of cardiovascular diseases. The aim of this study is to identify the impact of
      these investments during the period 2000-2006 from the subsequently published
      articles in scientific journals. METHODS: Using the identifying data of each
      project as search terms, all articles that resulted from these grants were
      located in the Spanish Indice Medico Espanol and Indice Bibliografico Espanol en
      Ciencias de la Salud databases, and in Science Citation Index-Expanded and
      Scopus. Descriptive statistical analysis of these articles included type of
      grant, number and amount awarded per year, and the recipient's sex and
      institutional affiliation. RESULTS: The Sociedad Espanola de Cardiologia awarded
      ?3,270,877 to 207 recipients, an average annual total of ?467,268. We identified
      231 publications that resulted from 123 (59.42%) of these grants. The average
      number of articles per grant awarded was 1.12, and 1.9 when taking into account
      only the awards that led to publication. CONCLUSIONS: During the period 2000 to
      2006, the Sociedad Espanola de Cardiologia/ Fundacion Espanola del Corazon
      (Spanish Heart Foundation) provided about ?500,000 per year to fund research
      grants, thereby contributing to the fight against cardiovascular diseases. Almost
      60% of grants have led to publications, 73% of which were published in
      international journals, and 91.34% in national or international journals with an
      impact factor in the Journal Citation Reports.

PMID- 21723656
TI  - Prognosis for patients with heart failure with preserved ejection fraction. Is it
      the same as low ejection fraction?

PMID- 21723657
TI  - Cardiovascular disease in the elderly.
AB  - The aging of the population worldwide will result in increasing numbers of
      elderly patients, among whom heart disease is the leading cause of death. Changes
      in cardiovascular physiology with normal aging and prevalent comorbidities result
      in differences in the effects of common cardiac problems as well as the response
      to their treatments. Patient-centered goals of care such as maintenance of
      independence and reduction of symptoms may be preferred over increased longevity.
      New less-invasive treatments are likely to improve outcomes in elderly patients
      who previously have been considered at prohibitive risk for traditional
      procedures. Clinical trials enrolling elderly patients are limited and
      recommendations for management from younger patients frequently lack evidence
      based support in patients aged >75 years.

PMID- 21723658
TI  - Perfluorinated phosphine oxide and sulfides as extractants for heavy metals and
      radionuclides.
AB  - New highly fluorinated monodentate and bidentate phosphine oxide compounds of the
      type {CF(3)(CF(2))(n)CH(2)CH(2)}(3)PO (n = 5, 9) and
      [{CF(3)(CF(2))(5)CH(2)CH(2)}(2)P(O)CH(2)CH(2)P(O){CH(2)CH(2)(CF(2))(5)CF(3)}]
      have been prepared. Their ability to extract a number of metals and radionuclides
      from aqueous solutions into perfluorinated solvents has been established and the
      extractable species investigated. All extractants extract the metals As(V),
      Cd(II), Co(II), Cr(VI), Hg(II), Pb(II), and Sn(II) with >75% removal. In
      addition, the radioisotopes (90)Sr(II), (133)Ba(II), and U(VI) have been
      investigated, whilst (59)Fe(III) has been used to model the extraction of
      plutonium. (133)Ba(II) shows a high distribution ratio for monodentate phosphine
      oxides, whilst for UO(2)(2+) and (59)Fe(III) bidentate phosphine oxides are
      superior.

PMID- 21723659
TI  - Sorption and desorption of Cd, Cu and Pb using biomass from an eutrophized
      habitat in monometallic and bimetallic systems.
AB  - This work examines the sorption capacity of a natural biomass collected from an
      irrigation pond. The biomass mainly consisted of a mixture of chlorophyte algae
      with caducipholic plants. Biosorption experiments were performed in monometallic
      and bimetallic solutions containing different metals commonly found in industrial
      effluents (Cd, Cu and Pb). The biosorption process was slightly slower in the
      binary system comparing with monometallic system which was related to competition
      phenomena between metal cations in solution. The biosorbent behaviour was
      quantified by the sorption isotherms fitting the experimental data to
      mathematical models. In monometallic systems, the Langmuir model showed a better
      fit with the following sorption order: Cu ~ Pb > Cd; and biomass-metal affinity
      order: Pb > Cd ~ Cu. In bimetallic systems, the binary-type Langmuir model was
      used and the sorption order obtained was: Pb ~ Cu > Cd. In addition, the
      effectiveness of the biomass was investigated in several sorption-desorption
      cycles using HCl and NaHCO(3). The recovery of metal was higher with HCl than
      with NaHCO(3), though the sorption uptake of the biomass was sensitively affected
      by the former desorption agent in subsequent sorption cycles.

PMID- 21723660
TI  - The influence of the operational environment on the efficiency of water
      utilities.
AB  - Adjusting for the operational environment in studies of performance measurement
      is very important, otherwise the analysis may lead to unrealistic scores,
      especially when its influence on costs is high, such as in the water utilities.
      In this paper, we study the influence of exogenous variables on the water
      utilities performance by applying conditional efficiency measures based on the
      order-m method and its probabilistic formulation. We use a sample of 66 water
      utilities operating between 2002 and 2008, representing about 70% of the
      Portuguese population. Our research suggests that inefficiency of Portuguese
      water utilities is substantial for some utilities: several exogenous variables
      might influence it considerably. For example, regulation has a positive influence
      on efficiency but when drinking water supply and wastewater services are provided
      by the same utility or when the wholesale and retail activities are provided
      together, the performance is lower. The effect of ownership is inconclusive and
      the variables residential customers, water source, peak factor, and density of
      customers have a mixed influence on performance which varies according to their
      scores.

PMID- 21723661
TI  - Soil organic carbon of degraded wetlands treated with freshwater in the Yellow
      River Delta, China.
AB  - Supplying freshwater is one of the important methods to help restore degraded
      wetlands. Changes in soil properties and plant community biomass were evaluated
      by comparing sites with freshwater treatment versus reference sites following
      freshwater addition to wetlands of the Yellow River Delta for 7 years. The
      results indicated that soil organic carbon (SOC) was significantly increased in
      all wetland sites that were treated with freshwater compared to the reference
      sites. The treatment wetlands had greater total nitrogen (TN), lower pH and
      electrical conductivity and higher water content in the soil compared to the
      reference wetlands. In general, the upper soil layer (0-20 cm) had greater SOC
      than the lower soil layer (20-40 cm). The increase of SOC in the freshwater
      reintroduction wetlands was higher in the Suaeda salsa plant community (mean +/-
      standard error) (6.89 +/- 0.63 g/kg) and Phragmites communis plant community
      (4.11 +/- 0.12 g/kg) than in the Tamarix chinensis plant community (1.40 +/- 0.31
      g/kg) in the upper soil layer. The differences were especially marked between the
      treated and reference wetlands for SOC and TN in the P. communis plant
      communities. The C:N ratio of the soil was significantly greater in the treated
      compared to the reference wetlands for the S. salsa plant community. Although the
      C: N ratios increased after treatment, they were all <25 suggesting that N
      availability was not limiting soil organic matter decomposition. Our results
      indicate that freshwater addition and the concomitant increase in soil moisture
      content enhances the accumulation of SOC in the Yellow River Delta.

PMID- 21723662
TI  - Effect of fire engulfment on thermal response of LPG tanks.
AB  - A model has been developed to predict the thermal response of liquefied-pressure
      gases (LPG) tanks under fire, and three-dimensional numerical simulations were
      carried out on a horizontal LPG tank which was 60% filled. Comparison between
      numerical predictions and published experimental data shows close agreement. The
      attention is focused on the influence of different fire conditions (different
      fire scenarios, various engulfing degrees and flame temperatures) on thermal
      response of LPG tanks. Potential hazard probabilities under different fire
      conditions were discussed by analyzing the maximum wall temperature and media
      energy after the internal pressure rose to the same value. It is found that the
      less severe fire scenario and lower engulfing case may lead to a greater
      probability of burst hazard because of the higher maximum wall temperature and
      media energy before the pressure relief valve (PRV) opens.

PMID- 21723663
TI  - Measuring chemical emissions from wet products--development of a new measurement
      technique.
AB  - A new approach for estimating chemical emissions from wet products has been
      developed. The concept of such approach is that emission rates can be estimated
      from the amount of target chemicals in the product as a function of evaporation
      time. Samples were placed under a laboratory fume hood under controlled
      conditions (surface air velocity and temperature). Weight losses of the product
      were monitored and residuals at different time intervals were chemically
      analyzed. Emission factors of the target chemicals were then calculated based on
      the weight losses and residual levels of the chemicals. To demonstrate the
      applicability of this approach, two wet products with very different physical
      characteristics, one liquid and one paste-like viscous fluid, were chosen.
      Emissions of two principle chemicals in the products,
      decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) were
      measured. The influences of initial sample weight, surface air velocity, and
      temperature were investigated. The calculated emission profiles were compared
      with those obtained from the chamber method. The described approach could be used
      as an alternative screening method for emission tests of wet products, especially
      for compounds with low vapour pressure when sink effect poses serious challenge
      in traditional chamber-based emission tests.

PMID- 21723664
TI  - The acquisition of fear of movement-related pain and associative learning: a
      novel pain-relevant human fear conditioning paradigm.
AB  - Current fear-avoidance models consider fear of pain as a key factor in the
      development of chronic musculoskeletal pain. Generally, the idea is that by
      virtue of the formation of associations or acquired propositional knowledge about
      the relation between neutral movements and pain, these movements may signal pain,
      and hence start to elicit defensive fear responses (eg, avoidance behavior). This
      assumption has never been investigated experimentally. Therefore, we developed a
      pain-relevant fear conditioning paradigm using a movement as a conditioned
      stimulus (CS) and a painful electrocutaneous stimulus as an unconditioned
      stimulus (US) to examine the acquisition of fear of movement-related pain in
      healthy subjects. In a within-subjects design, participants manipulated a
      joystick to the left/right in the experimental (predictable) condition, and
      upward/downward in the control (unpredictable) condition or vice versa. In the
      predictable condition, one movement direction (CS+), and not the other (CS-), was
      followed by painful stimuli. In the unpredictable condition, painful stimuli were
      always delivered during the intertrial interval. Both fear of movement-related
      pain ratings and eyeblink startle measures were more elevated in response to the
      CS+ than to the CS-, whereas no differences occurred between both unreinforced
      CSs in the control condition. Participants were slower initiating a CS+ movement
      than a CS- movement, while response latencies to CSs in the control condition did
      not differ. These data support the acquisition of fear of movement-related pain
      by associative learning. Results are discussed in the broader context of the
      acquisition of pain-related fear in patients with musculoskeletal pain.

PMID- 21723665
TI  - Molecular prevalence and characterization of Hepatozoon ursi infection in Indian
      sloth bears (Melursus ursinus).
AB  - Hepatozoon species are parasites that infect a wide variety of domestic and wild
      animals. The objective of the study was to detect the occurrence of Hepatozoon
      ursi in Indian sloth bears and to characterize the parasite based on phylogenetic
      analysis of the partial 18S rRNA gene sequence. Hepatozoon infection could be
      detected in 38 (70%) out of fifty-four blood samples of Indian sloth bears
      (captive and wild), suggestive of high prevalence of Hepatozoon infection in
      Indian sloth bears. Sequencing of partial 18S rRNA gene of the positive samples
      and BLAST analysis indicated that the nearest phylogenetic neighbour was H. ursi
      with which they exhibited 99-100% similarity. Additionally, Hepatozoon sp.
      isolated from wild sloth bears of India were identical to those in captive sloth
      bears and phylogenetically related to H. ursi reported from Japanese black bears
      from Japan. To our knowledge, this is the first report on the molecular
      characterization of H. ursi infection in Indian sloth bears.

PMID- 21723666
TI  - Severe methemoglobinaemia due to benzocaine-containing 'burn cream': two case
      reports in an adult and in a child.

PMID- 21723667
TI  - Abnormally rapid reversal learning and reduced response to antipsychotic drugs
      following ovariectomy in female rats.
AB  - Epidemiological and clinical life cycle studies indicate that favorable illness
      course and better response to antipsychotic drugs (APDs) in women with
      schizophrenia are positively correlated with estrogen levels. Accordingly, the
      estrogen hypothesis of schizophrenia proposes a neuroprotective role of estrogen
      in women vulnerable to schizophrenia. Previously we demonstrated in the rat that
      low levels of estrogen induced by ovariectomy led to disruption of latent
      inhibition (LI) reflecting impairment of selective attention, a core deficit of
      schizophrenia. LI disruption was reversed by 17beta-estradiol and the atypical
      APD clozapine, whereas the typical APD haloperidol was ineffective unless co
      administered with 17beta-estradiol. Here we aimed to extend these findings by
      testing ovariectomized rats in another selective attention task, discrimination
      reversal. Ovariectomy led to a loss of selective attention as manifested in
      abnormally rapid reversal. The latter was normalized by high dose of 17beta
      estradiol (150 MUg/kg) and clozapine (2.5mg/kg), but not by haloperidol
      (0.1mg/kg) or lower doses of 17beta-estradiol (10 and 50 MUg/kg). However, co
      administration of haloperidol with 17beta-estradiol (50 MUg/kg) was effective. In
      sham rats low 17beta-estradiol (10 MUg/kg) produced rapid reversal, while high
      17beta-estradiol (150 MUg/kg), haloperidol alone, or haloperidol-17beta-estradiol
      combination reduced reversal speed. Clozapine did not affect reversal speed in
      sham rats. These results strengthen our previous results in suggesting that
      schizophrenia-like attentional abnormalities as well as reduced response to APDs
      in female rats are associated with low level of gonadal hormones. In addition,
      they support the possibility that estrogen may have an antipsychotic-like action
      in animal models.

PMID- 21723668
TI  - Steroid sulfatase-deficient mice exhibit endophenotypes relevant to attention
      deficit hyperactivity disorder.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental
      condition characterised by inattention, impulsivity and hyperactivity; it is
      frequently co-morbid with anxiety and conduct disorders, sleep perturbation and
      abnormal consummatory behaviours. Recent studies have implicated the neurosteroid
      modulating enzyme steroid sulfatase (STS) as a modulator of ADHD-related
      endophenotypes. The effects of steroid sulfatase deficiency on homecage activity,
      feeding/drinking behaviours, anxiety-related behaviours (assayed in light-dark
      box and open field paradigms), social dominance and serum steroid hormone levels
      were determined by comparing 40,XY and 39,X(Y*)O mice. Subsequently, mice
      administered the steroid sulfatase inhibitor COUMATE acutely were compared to
      vehicle-treated mice on behavioural tasks sensitive to enzyme deficiency to
      dissociate between its developmental and ongoing effects. 39,X(Y*)O mice
      exhibited heightened reactivity to a novel environment, hyperactivity in the
      active phase, and increased water (but not food) consumption relative to 40,XY
      mice during a 24h period; the former group also demonstrated evidence for
      heightened emotional reactivity. There was no difference in social dominance
      between the 40,XY and 39,X(Y*)O mice. COUMATE administration had no effect on
      homecage activity, water consumption or anxiety measures in the open field.
      39,X(Y*)O mice exhibited significantly lower dehydroepiandrosterone (DHEA) serum
      levels than 40,XY mice, but equivalent corticosterone levels. Together with
      previous data, the present results suggest that steroid sulfatase may influence
      core and associated ADHD behavioural endophenotypes via both developmental and
      ongoing mechanisms, and that the 39,X(Y*)O model may represent a useful tool for
      elucidating the neurobiological basis of these endophenotypes.

PMID- 21723669
TI  - Victims of rape show increased cortisol responses to trauma reminders: a study in
      individuals with war- and torture-related PTSD.
AB  - Studies investigating cortisol responses to trauma-related stressors in patients
      with posttraumatic stress disorder (PTSD) have yielded inconsistent results,
      demonstrating that cortisol responses were enhanced or unaffected when confronted
      with trauma reminders. This study investigated the effect of the type of trauma
      experienced on both salivary and plasma cortisol responses during confrontation
      with trauma-related material. Participants were 30 survivors of war and torture,
      with and without rape among the traumatic events experienced. Participants of
      both groups (raped vs. non-raped) fulfilled DSM-IV criteria of PTSD. Plasma and
      salivary cortisol levels were measured at three time points during a standardized
      clinical interview: once before and twice after assessing individual traumatic
      experiences. Results show that groups did not differ in basal plasma and salivary
      cortisol levels. However, differential salivary cortisol responses were observed
      in PTSD patients who had been raped compared to those who had not been raped
      (p<.05) but had experienced an equal number of traumatic events and showed
      equally high PTSD symptom severity. Whereas salivary cortisol levels decreased in
      the course of the interview for the group with no past experience of rape
      (p<.05), those PTSD patients who had been raped showed a significant cortisol
      increase when reminded of their traumatic events (p<.001). This effect was not
      found in plasma cortisol. Our results indicate that the type of traumatic stress
      experienced contributes to cortisol responses during the confrontation with
      trauma-related material. We hypothesize, that the nearness of the perpetrator
      during the traumatic event might shape later psychophysiological responding to
      trauma reminders.

PMID- 21723670
TI  - Immunoglobulin M as a vaccine adjuvant.
AB  - Vaccines are effective in preventing disease by stimulating the immune system and
      sustaining an immune response towards eradication of pathogens and diseased
      cells. However, designing successful vaccines is not always straightforward. For
      a vaccine to be successful, antigen-presenting cells (APC) need to be stimulated,
      primarily by adjuvants, towards a sustained immune response through integration
      of the innate and adaptive (humoral and cellular) immune systems. Furthermore,
      there is an immediate need for safe and effective adjuvants. There has been
      significant progress in understanding the mechanisms on how vaccines work and the
      role of adjuvants, dendritic cells, and the toll-like receptor (TLR) pathway.
      Currently, different adjuvants are actively explored but the potential of the
      immunoglobulin M (IgM) as a vaccine adjuvant has been overlooked. This article
      hypothesizes how the IgM molecule could function as a vaccine adjuvant by acting
      as a "soluble" toll-like receptor (TLR) through the formation of an immune
      complex with antigen (Ag) and other components of the innate immune system. The
      complex should lead to sustained humoral and/or cell-mediated immune responses.
      Hypothetically, it is also possible that the Ag-IgM complex recruits other
      components of complement or other factors that can activate other members of the
      adaptive immune system. As it is now possible to produce commercial-scale
      quantities of monoclonal human IgM antibodies, understanding the role of the IgM
      in linking the innate and adaptive immune systems may lead to practical
      therapeutic applications.

PMID- 21723671
TI  - S-D-lactoylglutathione as a potential state marker for hemolysis.
AB  - Red blood cells represent the most abundant cell type in the blood and their
      energy production is exclusively dependent on glycolysis. However, about 0.1-0.4%
      of glucose is metabolized via methylglyoxal, a metabolite which is highly toxic
      to the cells. S-D-lactoylglutathione is an intermediate of methylglyoxal
      degradation by glyoxalases and is unable to cross cell membrane. Nevertheless, it
      is measurable in human plasma. This paper claims the introduction of the
      evaluation of plasma S-D-lactoylglutathione in hemolytic states and proposes its
      use as a state marker for such cases. According to this hypothesis, higher the
      rate of hemolysis in non-diabetic patients higher the level of S-D
      lactoylglutathione in their plasma. The measurement of S-D-lactoylglutathione in
      plasma, parallel with other parameters, can be a useful tool in distinguishing
      hemolytic states and in monitoring the effectiveness of treatment.

PMID- 21723672
TI  - Hypotheses for mechanisms linking shiftwork and cancer.
AB  - Shift work has been associated with various adverse health outcomes. In
      particular, there has been a recent flourish in investigating potential cancer
      risk associated with working night shifts and other shift schedules.
      Epidemiologic studies have revealed generally weak associations due to several
      methodological challenges such as lack of standard classifications of shift or
      night work. The field also has been hindered by a lack of clarity about the
      possible mechanisms by which shiftwork could have an effect on cancer risk. One
      possible mechanism is reduced production of melatonin caused by exposure to light
      at night. Although there is a growing body of evidence that provides some support
      for this mechanism, several other mechanisms also make sense from a biological
      point of view. Further, the relatively weak magnitude of the associations between
      light at night and melatonin level suggests that multiple factors may be
      operating along the pathway between shift work and adverse health consequences
      (including cancer risk). Here we propose four additional mechanisms that should
      be considered for a comprehensive investigation of these potential pathways.
      These are: phase shift; sleep disruption; lifestyle factors (such as poor quality
      diets, less physical activity and higher BMI); and lower vitamin D. Consideration
      of all these mechanisms is necessary in order to design effective preventative
      workplace strategies. In developed countries, approximately 20% of the population
      undertake shiftwork and, while we are unlikely to be able to eliminate shiftwork
      from current work practices, there are aspects of shiftwork that can be modified
      and there may be facets of individual susceptibility that we may be able to
      identify and target for prevention.

PMID- 21723673
TI  - The effect of vitamin D(3) supplementation on texture and oxidative stability of
      beef loins from steers treated with zilpaterol hydrochloride.
AB  - In this study, 10 young steers received no beta agonist (C), 50 animals all
      received zilpaterol hydrochloride (Z), with 1 group receiving Z while the other 4
      groups received Z and vitamin D(3) at the following levels (IU/animal /day) and
      durations before slaughter: 7 million for 3 days (3D7M) or 6 days (6D7M), 7
      million for 6 days with 7 days no supplementation (6D7M7N) and 1 million for 9
      days (9D1M). LD samples were vacuum-aged 14 days post mortem, and repacked in
      high-oxygen modified atmosphere (70% O(2)/30% CO(2)) for a further 7 days.
      Parameters included Warner Bratzler shear force (WBSF), myofibril fragment
      length, thiobarbituric acid reactive substances, free thiol levels, muscle fat,
      and instrumental colour parameters. When allowing for a conversion period of
      vitamin D(3) to its active metabolites, supplementing the zilpaterol treated
      steers with a high dosage of vitamin D(3) (6D7M7N) resulted in improved colour
      stability, higher stability towards protein oxidation and lower stability towards
      lipid oxidation.

PMID- 21723674
TI  - Effects of natural antimicrobials on inhibition of Listeria monocytogenes and on
      chemical, physical and sensory attributes of naturally-cured frankfurters.
AB  - Due to regulations for natural and organic processed meats, sodium nitrite and
      many antimicrobials cannot be used. Therefore, natural and organic processed
      meats are more susceptible to pathogenic bacterial growth, and natural
      alternatives to chemical preservatives are needed. Inhibition of Listeria
      monocytogenes, and quality characteristics of frankfurters manufactured with 3%
      cranberry powder, or with 1% or 2% cranberry powder each with either cherry
      powder (0.6%), lime powder (60 mg/kg), or a blend of cherry, lime and vinegar
      (1.4%) were investigated. Cranberry powder at 3% significantly reduced L.
      monocytogenes growth by 5.3 logCFU/g compared to the uncured co006Etrol (P
      <0.05). However, cranberry addition over 1% also resulted in significant product
      pH decline and negatively impacted the color, texture and sensory attributes of
      the frankfurters.

PMID- 21723675
TI  - Thumb basal joint arthroplasty using abductor pollicis longus tendon: an average
      5.5-year follow-up.
AB  - PURPOSE: The goal of this study was to evaluate the 4-year minimum (5.5-y
      average) results of trapeziectomy and ligament reconstruction using a modified
      Thompson technique with the abductor pollicis longus tendon for the primary
      treatment of advanced-stage basal joint arthritis (Eaton stages III and IV).
      METHODS: We evaluated 25 thumbs in 18 patients after ligament reconstruction
      arthroplasty for surgical treatment of advanced thumb basal joint arthritis.
      Treatment consisted of piecemeal excision of the entire trapezium, ligament
      reconstruction and interposition using the abductor pollicis longus tendon, and 8
      weeks of K-wire immobilization of the thumb metacarpal. We evaluated range of
      motion, lateral pinch, tip pinch, grip strength, and outcomes questionnaires
      including the Arthritis Impact Measurement Scales 2 Short Form before and at an
      average of 5.5 years after surgery. RESULTS: Seventeen of 18 patients reported
      excellent or good relief of pain and were satisfied with their operation, and all
      of the patients would have the operation again. Of the 25 thumbs, 24 adducted
      fully into the plane of the palm and opposed to the fifth metacarpal head.
      Preoperative and postoperative strength comparisons demonstrated an average
      increase in grip, key pinch, and tip pinch strength of 14%, 12%, and 6%,
      respectively. The outcomes data demonstrated noteworthy improvement in writing,
      buttoning a shirt, turning a key/lock, and arthritis pain categories.
      CONCLUSIONS: This technique restored a stable, pain-free thumb that yielded
      excellent strength and motion at an average of 5.5 years after the procedure.
      Compared with published reports of techniques that use hematoma distraction or
      harvest of all or part of the flexor carpi radialis tendon, this modified
      Thompson technique has similar pain relief, satisfaction, and motion but had less
      improvement in strength, which might have resulted from differences in the
      studied samples.

PMID- 21723676
TI  - [Fertility preservation in cancer women: a multidisciplinary approach].
AB  - Over the past two decades, major advances in diagnostic modalities and treatment
      have markedly improved rates of cure for adult cancers. As a consequence, the
      number of long-term survivors is increasing, and fertility preservation has
      become a major issue for young patient about to start treatment for cancer.
      Whether fertility preservation is a promising option, most of the technologies
      currently used are far from being well established or are even still
      experimental. Patients should be aware that no method guarantees success.
      Psychological and ethical impacts of fertility preservation are major concerns
      and should be included in the multidisciplinary approach of the patients.

PMID- 21723677
TI  - The aldehyde dehydrogenase 2 gene is associated with heroin dependence.
AB  - BACKGROUND: Determining the influences of genes involved in metabolizing dopamine
      and encoding dopamine receptors, such as the aldehyde dehydrogenase 2 (ALDH2) and
      dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1)
      genes, is critical for understanding addictive behavior. Therefore, we
      investigated the association between the ALDH2 and DRD2/ANKK1 Taq IA
      polymorphisms and heroin dependence. METHODS: Heroin-dependent Han Chinese
      patients (250) and healthy controls (312) were recruited. ALDH2 and DRD2/ANKK1
      Taq IA polymorphisms were genotyped. RESULTS: The frequency of ALDH2*1/*2 and
      *2/*2 genotypes was significantly higher in heroin-dependent patients than in
      controls, but the frequency of DRD2 Taq IA genotypes was not significantly
      different. Logistic regression analysis showed no significant interaction between
      ALDH2 and DRD2 Taq IA genotypes in patients. CONCLUSIONS: The ALDH2 polymorphism,
      but not the DRD2, was associated with heroin dependence.

PMID- 21723678
TI  - The estimation of the age of a blood stain using reflectance spectroscopy with a
      microspectrophotometer, spectral pre-processing and linear discriminant analysis.
AB  - A novel method for the non-destructive age determination of a blood stain is
      described. It is based on the measurement of the visible reflectance spectrum of
      the haemoglobin component using a microspectrophotometer (MSP), spectral pre
      processing and the application of supervised statistical classification
      techniques. The reflectance spectra of sample equine blood stains deposited on a
      glazed white tile were recorded between 1 and 37 days, using an MSP at
      wavelengths between 442 nm and 585 nm, under controlled conditions. The
      determination of age was based on the progressive change of the spectra with the
      aging of the blood stain. These spectra were pre-processed to reduce the effects
      of baseline variations and sample scattering. Two feature selection methods based
      on calculation of Fisher's weights and Fourier transform (FT) of spectra were
      used to create inputs into a statistical model based on linear discriminant
      analysis (LDA). This was used to predict the age of the blood stain and tested by
      using the leave-one-out cross validation method. When the same blood stain was
      used to create the training and test datasets an excellent correct classification
      rate (CCR) of 91.5% was obtained for 20 input frequencies, improving to 99.2% for
      66 input frequencies. A more realistic scenario where separate blood stains were
      used for the training and test datasets led to poorer successful classification
      due to problems with the choice of substrate but nevertheless up to 19 days a CCR
      of 54.7% with an average error of 0.71 days was obtained.

PMID- 21723679
TI  - beta-Hydroxybutyrate increases the pilocarpine-induced seizure threshold in young
      mice.
AB  - This study was designed to investigate the effects of beta-hydroxybutyrate (BHB)
      on pilocarpine-induced seizures in young mice. Eighty-five male, postnatal day
      21, ICR mice were used. All mice were pretreated with scopolamine methylbromide
      (1 mg/kg) 30 min prior to pilocarpine administration. Experimental mice (n=46)
      were injected intraperitoneally with BHB (20 mmol/kg), 15 min prior to
      pilocarpine administration; control animals (n=39) were administered normal
      saline. Pilocarpine (300 mg/kg) was then administered intraperitoneally to induce
      seizures. Mice were monitored for 2 h after pilocarpine injection, and seizure
      behavior grades were evaluated according to Racine's scale. All mice developed
      typical seizure behaviors of grade 3 or higher. Although the severity in terms of
      seizure behavior grade was not significantly different between groups, the mean
      (+/-SD) latency to the onset of seizure was significantly prolonged in BHB
      treated mice (5.15+/-2.19 min) compared with controls (2.95+/-1.06 min; p<0.001).
      This study demonstrates that treatment with BHB significantly prolongs the
      latency to the onset of seizures induced by pilocarpine in mice and suggests that
      BHB, one of the ketone bodies, may be direct anticonvulsant.

PMID- 21723680
TI  - [Evaluation of hospital stays linkage quality to study health spatial variation.
      a feasibility study in three French regions].
AB  - BACKGROUND: Since 2001, the French hospital stay databases (Programme de
      medicalisation des systemes d'information, PMSI) have included a unique and
      anonymous identifier in order to cross-link discharge abstracts from a given
      patient, within and across hospitals. These data could be used to estimate
      prevalence for some diseases at a territorial level provided that linkage quality
      is good enough. Few morbidity data are available at this scale. This study
      analyzes the link between linkage quality and hospitalization rates in three
      French regions (Picardy, Brittany and Provence-Alpes-Cote d'Azur-Paca). METHODS:
      We studied short stays in medicine-chirurgical-obstetrical units for the 2004
      2005 period (all stays, and stays with mention of cancer or asthma). To study
      linkage quality, the percentage of linkable stays (no error during the production
      of the anonymous identifier) was calculated at regional and territorial levels
      (areas used by regional health authorities). The interquartile range (IQR=third
      quartile-first quartile) of the percentage of linkable stays was calculated and
      the link between this percentage and standardized rates of people hospitalized at
      least once in 2004 or 2005 tested by Spearman correlation coefficients. RESULTS:
      For all stays, percentages of linkable stays were 94.4%, 96.6% and 97.0% in
      Picardy, Paca and Brittany respectively in 2004-2005. Geographical variation at
      the territorial level was higher in Picardy (IQR between 4 and 6) than in the two
      other regions (IQR between 1 and 2). The percentage of linkable stays was
      positively and significantly associated with the hospitalization rate for all
      stays and those with mention of cancer in Picardy only. CONCLUSION: According to
      these results, PMSI data earlier than 2006 should be used with precaution;
      linkage quality should be analyzed before making geographical or time comparisons
      of hospitalization rates. Comparisons cannot always be made. Other studies should
      be carried out in other regions, and to analyze recent trends in linkage quality.

PMID- 21723681
TI  - Is diffusion-weighted imaging useful in grading and differentiating
      histopathological subtypes of meningiomas?
AB  - PURPOSE: Meningiomas are mostly benign, however atypical or malignant subtypes
      with more aggressive clinical course and higher recurrence rates can also be
      seen. The purpose of this study was to determine whether histopathological
      subtypes of meningiomas could be assessed preoperatively using apparent diffusion
      coefficient (ADC) values. MATERIALS AND METHODS: Conventional magnetic resonance
      (MR) and diffusion-weighted (DW) imaging of 177 adult patients with
      pathologically proven meningiomas were retrospectively evaluated. Tumor size and
      the degree of associated edema were noted. The signal intensity of the lesions on
      DW imaging was evaluated and graded. Mean ADC values were obtained as the mean of
      measurements from three regions of interests within the mass. ADC ratios of
      meningioma/contralateral normal appearing subcortical parietal white matter were
      also calculated. RESULTS: The histopathological analysis revealed 135 benign, 37
      atypical and 5 malignant lesions. With classification according to the subtype,
      the mean ADC values and ratios of benign meningiomas were as 0.99+/-0.12*10(-3)
      mm(2)/s and 1.22+/-0.07, respectively. ADC values for atypical and malignant
      groups were both 0.84+/-0.1*10(-3) mm(2)/s. The ADC ratios were 1.05+/-0.1 and
      0.96+/-0.2 for atypical and malignant subtypes, respectively. There was no
      statistically significant difference between the mean ADC ratios of the three
      subtypes (ANOVA test; P>=0.05). Gender, age of the patients and tumor size showed
      no statistically significant difference between the different histological
      groups. CONCLUSION: DW MR imaging was not found to have any additional value in
      determining histological behaviour nor in differentiating histopathological
      subtypes of meningiomas.

PMID- 21723682
TI  - Emerging topics on the hip: ligamentum teres and hip microinstability.
AB  - Microinstability and ligament teres lesions are emergent topics on the hip
      pathology. These entities are an increasingly recognized cause of persistent hip
      pain and should be considered in the differential diagnosis of the patient with
      hip pain. Conventional (non-arthrographic) CT and MR have a very limited role in
      the evaluation of these entities. CTa and MRa have emerged as the modalities of
      choice for pre-operative imaging of ligamentum teres injuries and
      microinstability. To date, pre-operative imaging detection of these pathologies
      is not widespread but with appropriate imaging and a high index of suspicion,
      preoperative detection should improve. This article discusses current concepts
      regarding anatomy, biomechanics, clinical findings, diagnosis and treatment of
      ligament teres lesions and microinstability.

PMID- 21723683
TI  - WITHDRAWN: Acoustic radiation force impulse (ARFI) ultrasound imaging of breast
      lesions.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21723684
TI  - Carotid CT-angiography: low versus standard volume contrast media and low kV
      protocol for 128-slice MDCT.
AB  - Availability and utilization of computed tomography angiography has been
      increasing recently. We aimed to assess the effectiveness of low amount of
      contrast media and low kV value in order to reduce possible side effects of
      contrast media and to provide optimization of kV value in the evaluation of the
      carotid artery with multi-detector computed tomography angiography. Forty one
      patients were randomized into two groups. Contrast media was administered at a
      dose of 1 ml/kg in group A patients and of 0.5 ml/kg in group B patients. kV
      value of 120 in group A and 100 in group B were chosen. Bolus tracking technique
      was used. Attenuation values of certain arterial segments were measured, and
      values over 200 HU were considered as significant. North American Symptomatic
      Carotid Endartherectomy Trial criteria were utilized in the evaluation of
      stenosis. Image quality in arterial segments of all cases was found to be
      sufficient for diagnosis. Arterial attenuation values were found to be higher in
      group B than group A. When compared separately in all arterial segments, there
      was no statistically significant difference between the groups. For stenosis, 615
      arterial segments were evaluated. Moderate stenosis in eight segments and severe
      stenosis in three segments were identified in group A. Occlusion in three
      segments, severe stenosis in three segments, and moderate stenosis in 25 segments
      were detected in group B. Better image quality can be obtained, and the amount of
      contrast media can be reduced using low kV technique in carotid artery multi
      detector computed tomography angiography examination.

PMID- 21723685
TI  - Three spectroscopic techniques evaluated as a tool to study the effects of
      iodination of monoclonal antibodies, exemplified by rituximab.
AB  - Radioiodinated monoclonal antibodies have been used for radioimmunotherapeutic
      and radiodiagnostic purposes. Radioiodination of monoclonal antibodies may lead
      to deterioration of the immunoreactivity of the monoclonal antibody. Methods for
      the determination of the immunoreactivity, however, do not provide information
      about any structural changes of the radioconjugate which may influence the
      binding properties of the protein to the target antigen. Within this study we
      demonstrated the potential role of three alternative spectroscopic analytical
      techniques to characterize the structural changes emerging after iodination of
      rituximab. We conclude that techniques as liquid chromatography coupled to mass
      spectrometry, fluorescence emission spectrophotometry, and circular dichroism can
      provide valuable information about structural changes of a radiolabeled compound,
      e.g. during pharmaceutical development and for quality control.

PMID- 21723686
TI  - Late endovascular aneurysm repair infection presenting with juxatrenal aortic
      rupture treated with in situ aortic replacement.
AB  - Infection of an endovascular abdominal aneurysm repair (EVAR) is rare but has
      become more prevalent with the standardization of EVAR for treating infrarenal
      abdominal aortic aneurysms. The understanding of this complex aortic condition
      has improved but still remains to evolve. We present a patient with an EVAR
      infection manifesting with juxtarenal aortic rupture as a result of a urinary
      tract infection. This report describes an unusual presentation of an EVAR
      infection treated with in situ aortic reconstruction and provides >1 year of
      follow-up.

PMID- 21723687
TI  - Adeno-associated virus serotype 9-mediated overexpression of extracellular
      superoxide dismutase improves recovery from surgical hind-limb ischemia in BALB/c
      mice.
AB  - OBJECTIVE: Neovascularization is a physiologic repair process that partly depends
      on nitric oxide. Extracellular superoxide dismutase (EcSOD) is the major
      scavenger of superoxide. It is an important regulator of nitric oxide
      bioavailability and thus protects against vascular dysfunction. We hypothesized
      that overexpression of EcSOD in skeletal muscle would improve recovery from hind
      limb ischemia. METHODS: Adeno-associated virus serotype 9 (AAV9) vectors
      expressing EcSOD or luciferase (control) from the cytomegalovirus promoter were
      cross-packaged into AAV9 capsids and injected intramuscularly into the hind-limb
      muscles (1 * 10(11) viral genomes/limb) of 12-week-old mice. Ischemia was induced
      after intramuscular injections. Laser Doppler was used to measure limb perfusion
      on days 0, 7, and 14 after injection. Values were expressed as a ratio relative
      to the nonischemic limb. EcSOD expression was measured by Western blotting.
      Capillary density was documented by immunohistochemical staining for platelet
      endothelial cell adhesion molecule. Apoptosis was assessed by terminal
      deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end
      labeling and necrosis was visually evaluated daily. RESULTS: EcSOD expression was
      twofold upregulated in EcSOD treated vs control ischemic muscles at day 14.
      Capillary density (capillaries/fiber) was 1.9-fold higher in treated (1.65 +/-
      0.02) vs control muscle (0.78 +/- 0.17, P < .05). Recovery of perfusion ratio at
      day 14 after ischemia was 1.5-fold greater in EcSOD vs control mice (P < .05).
      The percentage of apoptotic nuclei was 1.3% +/- 0.4% in EcSOD-treated mice
      compared with 4.2% +/- 0.2% in controls (P < .001). Limb necrosis was also
      significantly lower in EcSOD vs control mice. CONCLUSION: AAV9-mediated
      overexpression of EcSOD in skeletal muscle significantly improves recovery from
      hind-limb ischemia in mice, consistent with improved capillary density and
      perfusion ratios in treated mice.

PMID- 21723688
TI  - Vacuum-assisted closure therapy with omental transposition for salvage of
      infected prosthetic femoral-distal bypass involving the femoral anastomosis.
AB  - Vascular graft infections are associated with the potential for devastating
      sequelae, including hemorrhage, septicemia, amputation, and death. Graft excision
      and debridement of the infected bed with revascularization via an extra-anatomic
      site or orthotopic vein bypass has been the traditional treatment of choice.
      Because the morbidity of these operations is substantial, less radical graft
      preservation techniques are desirable, such as myoplasty, omental flap
      transposition, and vacuum-assisted closure therapy. We report a patient with
      infection involving a prosthetic graft that was treated with vacuum-assisted
      closure and transposition of an omental tongue to enable coverage of the exposed
      graft.

PMID- 21723689
TI  - Survival after lung metastasectomy for colorectal cancer: importance of previous
      liver metastasis as a prognostic factor.
AB  - AIMS: To analyse patient survival after the resection of lung metastases from
      colorectal carcinoma and specifically to verify whether presence of liver
      metastasis prior to lung metastasectomy affects survival. METHODS: All patients
      who, between 1998 and 2008, underwent lung metastasectomy due to colorectal
      cancer were included in the study. Kaplan-Meier survival analysis was performed
      with the log-rank test and Cox regression multivariate analysis. RESULTS: During
      this period, 101 metastasectomies were performed on 84 patients. The median age
      of patients was 65.4 years, and 60% of patients were male. The 30-day mortality
      rate was 2%, and incidence of complications was 7%. The overall survival was 72
      months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of
      17 patients (20%) had previously undergone resection of liver metastasis. No
      significant differences were found in the distribution of what were supposed to
      be the main variables between patients with and without previous hepatic
      metastases. Multivariate analysis identified the following statistically
      significant factors affecting survival: previous liver metastasectomy (p = 0.03),
      tumour-infiltrated pulmonary lymph nodes (p = 0.04), disease-free interval >= 48
      months (p = 0.03), and presence of more than one lung metastasis (p < 0.01). In
      patients with previous liver metastasis, the shorter the time between primary
      colorectal surgery and the hepatectomy, the lower the survival rate after
      pulmonary metastasectomy (p = 0.048). CONCLUSIONS: A previous history of liver
      metastasis shortens survival after lung metastasectomy. The time between hepatic
      resection and lung metastasectomy does not affect survival; however, patients
      with synchronous liver metastasis and colorectal neoplasia have poorer survival
      rates than those with metachronous disease.

PMID- 21723690
TI  - Vaginal and pelvic recurrence rates based on vaginal cuff length in patients with
      cervical cancer who underwent radical hysterectomies.
AB  - AIMS: The objective of this study was to determine the association of vaginal
      cuff length (VCL) with vaginal and pelvic recurrence rates in patients with
      cervical cancer who underwent radical hysterectomies. MATERIALS AND METHODS: The
      clinicopathologic characteristics were collected from the medical records of 280
      patients with cervical cancer who underwent radical hysterectomies. The
      association of VCL with 3-year vaginal and pelvic recurrence rates was determined
      using a Z-test. The association of VCL with other clinicopathologic
      characteristics was also determined. RESULTS: The VCL was not associated with 3
      year vaginal and pelvic recurrence rates. The 3-year vaginal recurrence rate was
      0%-2% and the 3-year pelvic recurrence rate was 7%-8%, independent of VCL. The
      VCL and the age of patients had an inverse relationship. However, the VCL was not
      associated with histologic type, FIGO stage, clinical tumor size, tumor size in
      the surgical specimen, depth of invasion, lymphovascular space invasion,
      parametrial involvement, lymph node involvement, and adjuvant therapy. One
      hundred ninety of 280 patients (68%) underwent adjuvant therapies following
      radical hysterectomies. CONCLUSION: Although it is limited by the high rate of
      adjuvant therapy, the current study suggested that the VCL following radical
      hysterectomy in patients with cervical cancer was not associated with vaginal and
      pelvic recurrence rates.

PMID- 21723691
TI  - Interleukin 1 receptor antagonist reduces lethality and intestinal toxicity of 5
      Fluorouracil in a mouse mucositis model.
AB  - Chemotherapy induced intestinal mucositis is still an unmet medical problem. 5
      fluorouracil (5-Fu), a chemotherapy drug, was used to create the animal model of
      mucositis. Global gene expression array was applied to identify genetic signals
      involved in the pathogenesis of mucositis. Interleukin 1 receptor antagonist (IL
      1Ra) was one of the candidates with the characteristic gene expression profile.
      Its temporal expression pattern correlated to the damage and regeneration phase
      of the small intestine after a single injection of 5-Fu to mice. Administration
      of recombinant IL-1Ra to the mouse model of intestinal mucositis induced by 5-Fu
      demonstrated its therapeutic effects to the symptoms and pathology of the
      disease. The IL-1Ra treatment reduced the acute lethality, accelerated their body
      weight recovery, and eliminated severe diarrhea. The symptomatic benefits were
      supported by the pathological benefits, in which the mice treated with IL-1Ra has
      less damage and faster recovery of the structure integrity of their small
      intestine than that of the mice treated with vehicle control. To deliver the
      therapeutics to the unmet medical condition, further mechanism and translational
      studies of IL-1Ra in the settings of chemotherapy induced intestinal mucositis
      are warranted.

PMID- 21723692
TI  - 2010 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Training
      Standards and Maintenance of Competency in Adult Clinical Cardiac
      Electrophysiology.
AB  - The last guidelines on training for adult cardiac electrophysiology (EP) were
      published by the Canadian Cardiovascular Society in 1996. Since then, substantial
      changes in the knowledge and practice of EP have mandated a review of the
      previous guidelines by the Canadian Heart Rhythm Society, an affiliate of the
      Canadian Cardiovascular Society. Novel tools and techniques also now allow
      electrophysiologists to map and ablate increasingly complex arrhythmias
      previously managed with pharmacologic or device therapy. Furthermore, no formal
      attempt had previously been made to standardize EP training across the country.
      The 2010 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Training
      Standards and Maintenance of Competency in Adult Clinical Cardiac
      Electrophysiology represent a consensus arrived at by panel members from both
      societies, as well as EP program directors across Canada and other select
      contributors. In describing program requirements, the technical and cognitive
      skills that must be acquired to meet training standards, as well as the minimum
      number of procedures needed in order to acquire these skills, the new guidelines
      provide EP program directors and committee members with a template to develop an
      appropriate curriculum for EP training for cardiology fellows here in Canada.

PMID- 21723693
TI  - Noninvasive prediction of left ventricular end-diastolic pressure in patients
      with coronary artery disease and preserved ejection fraction.
AB  - BACKGROUND: The aim of this study was to compare 3 different available methods
      for estimating left ventricular end-diastolic pressure (LVEDP) noninvasively in
      patients with coronary artery disease and preserved left ventricular ejection
      fraction (EF). METHODS: We used 3 equations for noninvasive estimation of LVEDP:
      The equation of Mulvagh et al., LVEDP(1) = 46 - 0.22 (IVRT) - 0.10 (AFF) - 0.03
      (DT) - (2 / E/A) + 0.05 MAR; the equation of Stork et al., LVEDP(2) = 1.06 +
      15.15 * Ai/Ei; and the equation of Abd-El-Aziz, LVEDP(3) = [0.54 (MABP) * (1 -
      EF)] - 2.23. ( ABBREVIATIONS: A, A-wave velocity; AFF, atrial filling fraction;
      Ai, time velocity integral of A wave; DT, deceleration time; E, E-wave velocity;
      Ei, time velocity integral of E wave; IVRT, isovolumic relaxation time; MABP,
      mean arterial blood pressure; MAR, time from termination of mitral flow to the
      electrocardiographic R wave; Ti, time velocity integral of total wave.) RESULTS:
      LVEDP measured by catheterization was correlated with LVEDP(1) (r = 0.52, P <
      0.001), LVEDP(2) (r = 0.31, P < 0.05), and LVEDP(3) (r = 0.81, P < 0.001).
      CONCLUSIONS: The equation described by Abd-El-Aziz, LVEDP = [0.54 MABP * (1 -
      EF)] - 2.23, appears to be the most accurate, reliable, and easily applied method
      for estimating LVEDP noninvasively in patients with preserved left ventricular
      ejection fraction and an LVEDP < 20 mm Hg.

PMID- 21723694
TI  - Pelvic reconstruction with a free vascularized distal femur for revision total
      hip arthroplasty.
AB  - The reconstruction of massive structural acetabular defects after revision
      arthroplasty presents a unique challenge to the orthopedic surgeon. This report
      describes such a salvage procedure where an autologous vascularized distal femur
      was used to reconstruct acetabular bone stock with subsequent implantation of a
      total femoral endoprosthetic replacement that uses a constrained cup and a hinged
      total knee system. At 2 years of follow-up, there is a good functional result
      with full incorporation of the graft.

PMID- 21723695
TI  - Benefits of prolonged postoperative cyclooxygenase-2 inhibitor administration on
      total knee arthroplasty recovery: a double-blind, placebo-controlled study.
AB  - A double-blind, placebo-controlled study of a selective cyclooxygenase (COX)-2
      inhibitor administered in 107 patients for 6 weeks after total knee arthroplasty
      was done to determine any benefits. All patients received celecoxib
      preoperatively and during hospitalization. At hospital discharge, patients were
      randomized to receive celecoxib or placebo for 6 weeks. Narcotic use, knee
      flexion, Knee Society Score, Oxford Knee Score, and Short-Form 12 scores were
      determined preoperatively and at postoperative intervals to 1 year. Visual analog
      scale scores documented pain at rest, at night, and with activities. The
      celecoxib group used fewer narcotics and had significantly better visual analog
      scale scores, knee flexion, Knee Society Score scores, Oxford Knee Score scores,
      and Short-Form 12 physical composite scores than the placebo group. Knee flexion
      remained significantly improved through 1 year. These results demonstrate that
      patients who took celecoxib for 6 weeks after total knee arthroplasty had a less
      painful and more rapid recovery.

PMID- 21723696
TI  - Interface micromotion of uncemented femoral components from postmortem retrieved
      total hip replacements.
AB  - Axial torsional loads representative of gait and stair climbing conditions were
      applied to transverse sections of 8 uncemented postmortem retrievals and a high
      resolution imaging system with digital image correlation was used to measure
      local micromotion along the bone-implant interface. For 7 components that were
      radiographically stable, there was limited micromotion for gait loading (1.42 +/-
      1.33 MUm) that increased significantly (P = .0032) for stair climb loading (7.32
      +/- 9.96 MUm). A radiographically loose component had motions on the order of 2.3
      mm with gait loading. There was a strong inverse relationship between the amount
      of bone-implant contact (contact fraction) (P = .001) and micromotion. The
      uncemented components had greater contact fraction (41.8% +/- 14.4% vs 11.5% +/-
      10.2%, P = .0033) and less median micromotion (0.81 +/- 0.79 MUm vs 28.8 +/- 51.1
      MUm) compared to a previously reported study of cemented retrievals.

PMID- 21723697
TI  - Prospective randomized comparison of high-flex and standard rotating platform
      total knee arthroplasty.
AB  - We sought to determine if the rotating platform (RP) high-flex design provides
      improved flexion compared with the standard RP total knee. A total of 142
      patients were randomized to receive an RP flex (RP-F) or RP TKA. Supine flexion
      was measured with a goniometer and lateral x-ray. There was no difference in
      flexion measured at any interval between groups (1-year clinical flexion RP,
      124.0 degrees ; RP-F, 124.2 degrees ; P = .949; 1-year x-ray flexion RP, 117.9
      degrees ; RP-F, 117.6 degrees ; P = .985). There was no difference between groups
      comparing the improvement from preoperative to 1-year postoperative flexion (RP
      F, 5.2 degrees ; RP, 4.1 degrees ; P = .580). There were 13 patients with
      postoperative patellar crepitus, with more in the RP-F group (RP-F, 11 patients
      [16.7%]; RP, 2 patients [3.2%]; P = .017). Owing to these results, coupled with
      the increased bone resection and higher cost, we no longer routinely use the RP-F
      design.

PMID- 21723698
TI  - What is the true incidence of dental pathology in the total joint arthroplasty
      population?
AB  - One million total joint arthroplasties (TJAs) are performed annually in the
      United States. The incidence of oral disease has not been documented in this
      population. To understand the scope of disease, a descriptive longitudinal
      population-based study sought to define the true incidence of dental pathology in
      the TJA population. One hundred consecutive TJA patients from a dedicated
      arthroplasty practice were sent for dental clearance, including oral examination,
      cleaning, radiographs, and treatment of active decay. The incidence of pathology
      was documented. Of 10 patients, 23 (23%) were treated before being cleared for
      arthroplasty. Sixty-six procedures were performed--2.9 problems per patient. No
      patient developed TJA infection. Routine preoperative dental clearance revealed
      23% incidence of pathology, and no patient developed TJA infection.

PMID- 21723699
TI  - Metal-on-metal vs metal-on-improved polyethylene bearings in total hip
      arthroplasty.
AB  - Major weaknesses of total hip arthroplasty (THA) in the 20th century were
      polyethylene wear and dislocation. Efforts to improve THA took several directions
      including improvement of polyethylene and use of metal-on-metal (MoM)
      articulations. Metal-on-metal articulations showed excellent early results, but
      concerns mount over hypersensitivity and increasing failure. This study compares
      our experience with MoM and metal-on-improved polyethylene (MoIP) bearings in
      primary THA. We identified 1362 patients undergoing 1589 MoM THA and 693 patients
      undergoing 779 MoIP THA (all compression molded and sterilized in argon).
      Overall, more MoM than MoIP cups have been revised (4.0% vs 2.2%; P = .0241).
      Revision incidence for infection was similar; higher with MoM for loosening (P =
      .0020), metal complication (P = .0017), and combined aseptic causes (P = .0067);
      and higher for dislocation in MoIP (P = .0246). Metal-on-improved polyethylene
      devices had superior results compared with MoM in this study. Furthermore, 5 MoIP
      revisions were liner exchanges, a conservative option not available with MoM.

PMID- 21723700
TI  - Readmission and length of stay after total hip arthroplasty in a national
      Medicare sample.
AB  - Evaluation of hospital readmissions after total hip arthroplasty may help improve
      patient safety and cost reduction. This study investigates the rates and reasons
      for readmission as well as length of hospital stay (LOS) for 1802 total hip
      arthroplasty patients from 2002 to 2007. Data were abstracted from the Medicare
      Patient Safety Monitoring System. The overall 30-day rate of readmission was
      6.8%. There was no difference in readmission rate from 2002 to 2004 (7.1%) to
      2005 to 2007 (6.3%) (odds ratio, 0.90; 95% confidence interval, 0.63-1.30; P =
      .58). The overall mean LOS was 4.2 +/- 2.2 days. There was a significant
      reduction in LOS from 2002 to 2004 (4.4 +/- 2.5 days) to 2005 to 2007 (3.8 +/-
      1.7 days) (odds ratio, 1.28; 95% confidence interval, 1.25-1.31; P < .0001). The
      most common causes for readmission were cardiac related. A reduction in LOS was
      not associated with an increase in the rate of readmission in this sample.
      Efforts to optimize cardiac status before discharge may lead to lower rates of
      readmission in the future.

PMID- 21723701
TI  - Modern total hip arthroplasty in patients younger than 21 years.
AB  - Total hip arthroplasty (THA) is not commonly performed in adolescents. However,
      it may be the only option for pain control with continued mobility for advanced
      disease. We report our experience with modern alternative-bearing THA in patients
      younger than 21 years. Twenty-one THAs (18 patients) were followed. Preoperative
      and postoperative Harris hip scores were recorded, and radiographs were reviewed.
      Average follow-up was 49 months (range, 25-89). Underlying etiology was
      chemotherapy-induced osteonecrosis (33%), steroid-induced osteonecrosis (29%),
      sickle cell disease (24%), and chronic dislocation (14%). Articulation bearings
      were ceramic/ceramic (67%), metal/highly cross-linked polyethylene (29%), and
      metal resurfacing (5%). Mean age was 18 years (range, 13-20). Harris hip scores
      improved from 43.6 to 83.6 (P < .001). At final follow-up, there was no
      radiographic loosening; 1 THA was revised for a cracked ceramic liner. At
      intermediate-term follow-up, clinical and radiographic results are favorable
      after alternative-bearing THA in patients younger than 21 years.

PMID- 21723702
TI  - The flexion-extension axis of the knee and its relationship to the rotational
      orientation of the tibial plateau.
AB  - We measured the optimal rotational alignment of the tibial component with respect
      to anatomic landmarks. Kinematic data were collected from functional maneuvers
      simulated in 20 cadaveric knees mounted in a joint simulator. The axis of knee
      motion was calculated for squatting and lunging activities over the interval of
      30 degrees  to 90 degrees  of knee flexion. We then examined the accuracy and
      variability of 5 different anatomic axes in predicting the direction of knee
      motion. No one landmark guaranteed correct alignment of the tibial component and
      most predictors were highly variable (range, 6 degrees -21 degrees ). The most
      accurate indicators were the medial third of the tibial tubercle (average error:
      squatting: 3.5 degrees  external rotation; lunging: 9.5 degrees ), and the medial
      lateral axis of the resected tibial surface (6.7 degrees  and 1.1 degrees 
      internal rotation). The correct alignment of the tibial component can be best
      achieved by splitting the difference between these landmarks to eliminate
      placement of the component in excessive external and excessive internal rotation.

PMID- 21723703
TI  - Comparison of radiographic alignment of imageless computer-assisted surgery vs
      conventional instrumentation in primary total knee arthroplasty.
AB  - A total of 208 patients were enrolled in a multicenter, prospective randomized,
      institutional review board-approved study that compared preoperative surgical
      plan to postoperative 2-dimensional radiographic alignment measured by a blinded
      reviewer for primary total knee arthroplasty (TKA) implanted using computer
      assisted surgery (CAS) compared with conventional TKA instrumentation. The
      results demonstrated a statistically significant improvement in the coronal
      tibial component alignment (P < .03) and failed to demonstrate a statistically
      significant improvement in the mechanical axis, femoral coronal/sagittal, and
      tibial sagittal alignment. Knee Society Score knee and function scores and 6
      minute walk test were equivalent between the 2 treatment groups at all
      postoperative intervals. There was a statistically significant increase in the
      skin-skin time (P < .0001) and the time until first bone cut (P < .0001) for the
      CAS knees compared with those implanted with conventional instrumentation. The
      use of CAS in this randomized clinical trial conducted at high-volume centers did
      not offer a clinically meaningful improvement in postoperative alignment,
      clinical, functional, or safety outcomes compared with conventional TKA.

PMID- 21723704
TI  - Genetic algorithm pruning of probabilistic neural networks in medical disease
      estimation.
AB  - A hybrid model consisting of an Artificial Neural Network (ANN) and a Genetic
      Algorithm procedure for diagnostic risk factors selection in Medicine is proposed
      in this paper. A medical disease prediction may be viewed as a pattern
      classification problem based on a set of clinical and laboratory parameters.
      Probabilistic Neural Network models were assessed in terms of their
      classification accuracy concerning medical disease prediction. A Genetic
      Algorithm search was performed to examine potential redundancy in the diagnostic
      factors. This search led to a pruned ANN architecture, minimizing the number of
      diagnostic factors used during the training phase and therefore minimizing the
      number of nodes in the ANN input and hidden layer as well as the Mean Square
      Error of the trained ANN at the testing phase. As a conclusion, a number of
      diagnostic factors in a patient's data record can be omitted without loss of
      fidelity in the diagnosis procedure.

PMID- 21723705
TI  - Snap-drift neural network for self-organisation and sequence learning.
AB  - This paper presents two novel neural networks based on snap-drift in the context
      of self-organisation and sequence learning. The snap-drift neural network employs
      modal learning that is a combination of two modes; fuzzy AND learning (snap), and
      Learning Vector Quantisation (drift). We present the snap-drift self-organising
      map (SDSOM) and the recurrent snap-drift neural network (RSDNN). The SDSOM uses
      the standard SOM architecture, where a layer of input nodes connects to the self
      organising map layer and the weight update consists of either snap (min of input
      and weight) or drift (LVQ, as in SOM). The RSDNN uses a simple recurrent network
      (SRN) architecture, with the hidden layer values copied back to the input layer.
      A form of reinforcement learning is deployed in which the mode is swapped between
      the snap and drift when performance drops, and in which adaptation is
      probabilistic, whereby the probability of a neuron being adapted is reduced as
      performance increases. The algorithms are evaluated on several well known data
      sets, and it is found that these exhibit effective learning that is faster than
      alternative neural network methods.

PMID- 21723706
TI  - A just-in-time adaptive classification system based on the intersection of
      confidence intervals rule.
AB  - Classification systems meant to operate in nonstationary environments are
      requested to adapt when the process generating the observed data changes. A
      straightforward form of adaptation implementing the instance selection approach
      suggests releasing the obsolete data onto which the classifier is configured by
      replacing it with novel samples before retraining. In this direction, we propose
      an adaptive classifier based on the intersection of confidence intervals rule for
      detecting a possible change in the process generating the data as well as
      identifying the new data to be used to configure the classifier. A key point of
      the research is that no assumptions are made about the distribution of the
      process generating the data. Experimental results show that the proposed adaptive
      classification system is particularly effective in situations where the process
      is subject to abrupt changes.

PMID- 21723707
TI  - Doppler classification of diastolic dysfunction.

PMID- 21723708
TI  - Role of Transesophageal Echocardiography Compared to Computed Tomography in
      Evaluation of Pulmonary Vein Ablation for Atrial Fibrillation (ROTEA study).
AB  - BACKGROUND: Computed tomography (CT) is the gold standard for assessing pulmonary
      vein (PV) anatomy and stenosis after ablation for atrial fibrillation (AF), but
      radiation exposure can be a concern. Transesophageal echocardiography (TEE)
      provides anatomic and functional assessment of the PVs, although no study has
      prospectively compared findings on TEE with those on CT. METHODS: The Role of
      Transesophageal Echocardiography Compared to Computed Tomography in Evaluation of
      Pulmonary Vein Ablation for Atrial Fibrillation (ROTEA) study was a prospective,
      single-blinded observational study of patients with paroxysmal or persistent AF
      undergoing ablation. TEE and CT were performed immediately before and 3 months
      after AF ablation. The study included 43 patients (84% men; mean age, 56 +/- 11
      years). RESULTS: In the preprocedural study, TEE identified 98% of PVs with
      adequate Doppler measurements obtained. After ablation, no moderate or severe PV
      stenosis was detected on CT, and a 30% to 50% reduction in luminal diameter was
      seen in 5% of studied veins. Functional PV stenosis by pulsed-wave Doppler was
      seen in two veins on TEE. PV diameters decreased after ablation by 0.20 +/- 0.03
      and 0.22 +/- 0.03 cm as measured by CT and TEE, respectively (P < .001). However,
      TEE underestimated PV ostial dimensions compared with CT, especially for the
      inferior PVs. Severe spontaneous echo contrast and low left atrial appendage
      emptying velocities, were identified in 10% of patients in sinus rhythm after
      ablation. CONCLUSIONS: In the ROTEA study, TEE was feasible in assessing PVs
      before and after ablation, providing both anatomic and functional information
      that complemented CT. PV ostial dimensions after ablation can be monitored using
      either modality, although TEE underestimates PV dimensions, especially for the
      inferior veins.

PMID- 21723709
TI  - Micronutrients.

PMID- 21723710
TI  - Treatment of chronic mandibular dislocations using a new miniplate.
AB  - Temporomandibular joint (TMJ) dislocation is defined as an excessive forward
      movement of the condyle beyond the articular eminence with complete separation of
      the articular surfaces and fixation in that position. The aim of this study was
      to describe a modified miniplate designed for treating chronic mandibular
      dislocations and evaluate the results of its placement in one patient, who was
      followed for 18 months. The treatment of chronic mandibular dislocation using
      this modified miniplate was shown to be efficient in relation to the
      postoperative maximal mouth opening, recurrence and articular function.

PMID- 21723711
TI  - Osteolytic mandible presenting as an initial manifestation of an adult acute
      lymphoblastic leukaemia.
AB  - A case of adult acute lymphoblastic leukaemia is reported. A 35-year-old male
      presented with an osteolytic lesion of the mandible. There was no definitive
      involvement in other craniofacial bones. A panoramic radiograph taken 4 months
      previously showed no bony involvement. A complete blood count showed a slightly
      decreased red blood cell count, but normal white blood cell count, white blood
      cell differential count and platelet count. Routine chemistry revealed
      hypercalcemia with an increased level of parathyroid hormone-related protein.
      Histopathological examination of bone marrow biopsy confirmed the diagnosis of
      acute lymphoblastic leukaemia.

PMID- 21723712
TI  - Magnetic resonance imaging studies in unipolar depression: systematic review and
      meta-regression analyses.
AB  - Previous meta-analyses of structural MRI studies have shown diffuse cortical and
      sub-cortical abnormalities in unipolar depression. However, the presence of
      duplicate publications, recruitment of particular age groups and the selection of
      specific regions of interest means that there is uncertainty about the balance of
      current research. Moreover, the lack of systematic exploration of highly
      significant heterogeneity has prevented the generalisability of finding. A
      systematic review and random-effects meta-analysis was carried out to estimate
      effect sizes. Possible publication bias, and the impact of various study design
      characteristics on the magnitude of the observed effect size were systematically
      explored. The aim of this study was 1) to include structural MRI studies
      systematically comparing unipolar depression with bipolar disorder and healthy
      volunteers; 2) to consider all available structures of interest without specific
      age limits, avoiding data duplication, and 3) to explore the influence of factors
      contributing to the measured effect sizes systematically with meta-regression
      analyses. Unipolar depression was characterised by reduced brain volume in areas
      involved in emotional processing, including the frontal cortex, orbitofrontal
      cortex, cingulate cortex, hippocampus and striatum. There was also evidence of
      pituitary enlargement and an excess of white matter hyperintensity volume in
      unipolar depression. Factors which influenced the magnitude of the observed
      effect sizes were differences in methods, clinical variables, pharmacological
      interventions and sample age.

PMID- 21723713
TI  - [Management of neuropathic pain in children: guidelines for good clinical
      practice].
AB  - Neuropathic pain exists in children and its incidence is often underestimated due
      to the lack of knowledge on the existence and the diagnosis of this pain.
      Although the semiological characteristics can be compared to those of the adult
      (allodynia, hypoesthesia, burning and stabbing sensations), their etiology often
      differs, and pain treatments are more limited because of a lack of
      pharmacological data and the absence of clinical studies. Therapeutic management
      is sometimes insufficient and requires better knowledge of this entity. Based on
      the June 2009 recommendations of the French Agency for Food and Drug Safety
      (Afssaps) (drug therapy in acute and chronic pain in children), this article
      presents a review of the data available in the literature on the subject, taking
      into account expert opinion and proposing clinical recommendations of good
      practice for the recognition and the treatment of neuropathic pain in children.

PMID- 21723714
TI  - Current developments in specialty training.

PMID- 21723715
TI  - Clinical examination does not assist in the detection of systemic relapse of
      testicular germ cell tumour.
AB  - AIMS: Patients on follow-up after orchidectomy or chemotherapy for testicular
      germ cell tumours follow a protocol of outpatient appointments and investigations
      designed to detect relapse. We wanted to investigate the contribution of clinical
      examination to patient management. MATERIALS AND METHODS: The notes of 70
      consecutive patients who suffered a first systemic relapse of their germ cell
      tumour within the last 10 years were studied to determine how the relapse was
      detected. Second testicular tumours were excluded. RESULTS: Of the 69 patients
      whose notes were available, only one had a significant finding on physical
      examination, concurrent with abnormal markers. CONCLUSIONS: We suggest that, for
      patients following a planned programme of appointments and investigations,
      physical examination rarely contributes to the detection of systemic relapse in
      the follow-up of testicular germ cell tumours. It may therefore be possible to
      reconfigure follow-up to focus on investigations and telephone contact. We
      estimate that this change might be appropriate for 40% of attendances and might
      be welcomed by patients, many of whom find follow-up burdensome. If such a change
      were considered, patient education would be essential to ensure continuing
      compliance with the follow-up protocol.

PMID- 21723716
TI  - Comparison of advanced iterative reconstruction methods for SPECT/CT.
AB  - AIM: Corrective image reconstruction methods which produce reconstructed images
      with improved spatial resolution and decreased noise level became recently
      commercially available. In this work, we tested the performance of three new
      software packages with reconstruction schemes recommended by the manufacturers
      using physical phantoms simulating realistic clinical settings. METHODS: A
      specially designed resolution phantom containing three (99m)Tc lines sources and
      the NEMA NU-2 image quality phantom were acquired on three different SPECT/CT
      systems (General Electrics Infinia, Philips BrightView and Siemens Symbia T6).
      Measurement of both phantoms was done with the trunk filled with a (99m)Tc-water
      solution. The projection data were reconstructed using the GE's Evolution for
      Bone((r)), Philips Astonish((r)) and Siemens Flash3D((r)) software. The
      reconstruction parameters employed (number of iterations and subsets, the choice
      of post-filtering) followed theses recommendations of each vendor. These results
      were compared with reference reconstructions using the ordered subset expectation
      maximization (OSEM) reconstruction scheme. RESULTS: The best results (smallest
      value for resolution, highest percent contrast values) for all three packages
      were found for the scatter corrected data without applying any post-filtering.
      The advanced reconstruction methods improve the full width at half maximum (FWHM)
      of the line sources from 11.4 to 9.5mm (GE), from 9.1 to 6.4mm (Philips), and
      from 12.1 to 8.9 mm (Siemens) if no additional post filter was applied. The total
      image quality control index measured for a concentration ratio of 8:1 improves
      for GE from 147 to 189, from 179. to 325 for Philips and from 217 to 320 for
      Siemens using the reference method for comparison. The same trends can be
      observed for the 4:1 concentration ratio. The use of a post-filter reduces the
      background variability approximately by a factor of two, but deteriorates
      significantly the spatial resolution. CONCLUSIONS: Using advanced reconstruction
      algorithms the largest improvement in image resolution and contrast is found for
      the scatter corrected slices without applying post-filtering. The user has to
      choose whether noise reduction by post-filtering or improved image resolution
      fits better a particular imaging procedure.

PMID- 21723717
TI  - Nod factors stimulate seed germination and promote growth and nodulation of pea
      and vetch under competitive conditions.
AB  - Nod factors are lipochitooligosaccharide (LCO) produced by soil bacteria commonly
      known as rhizobia acting as signals for the legume plants to initiate symbiosis.
      Nod factors trigger early symbiotic responses in plant roots and initiate the
      development of specialized plant organs called nodules, where biological nitrogen
      fixation takes place. Here, the effect of specific LCO originating from flavonoid
      induced Rhizobium leguminosarum bv. viciae GR09 culture was studied on
      germination, plant growth and nodulation of pea and vetch. A crude preparation of
      GR09 LCO significantly enhanced symbiotic performance of pea and vetch grown
      under laboratory conditions and in the soil. Moreover, the effect of GR09 LCOs
      seed treatments on the genetic diversity of rhizobia recovered from vetch and pea
      nodules was presented.

PMID- 21723718
TI  - Cis-9,trans-11-conjugated linoleic acid promotes neuronal differentiation through
      regulation of Hes6 mRNA and cell cycle in cultured neural stem cells.
AB  - Conjugated linoleic acids (CLAs) are positional and geometrical isomers of
      linoleic acid (LA). Cis-9,trans-11-CLA (CLA), the main isomer of CLAs in foods
      derived from ruminants, has several beneficial effects for humans and animals;
      however, its effects on the central nervous system are largely unknown. In this
      study, we investigated the effects of LA and CLA on neuronal differentiation of
      neural stem cells (NSCs). NSCs cultured with or without LA and CLA were assessed
      by immunofluorescence staining, mRNA measurement of basic helix-loop-helix
      transcription factors and cyclin-dependent kinase inhibitors by real-time PCR,
      BrdU incorporation analysis and flow cytometry analysis. In NSCs treated with
      CLA, the number of Tuj-1-positive cells (neurons) and the mRNA expression levels
      of Hes6, MAP2, p21(cip1) and p27(kip1) increased, while the proportion of S-phase
      cells decreased; compared with the control, no change was demonstrated in NSCs
      treated with LA. These results suggest that CLA promotes neuronal differentiation
      by increasing, in part, the expression of Hes6 mRNA and by activating p21(cip1)
      and p27(kip1) to arrest cell cycle.

PMID- 21723719
TI  - Use of a tracheoscopic ventilation tube for endotracheal intubation in the
      difficult airway.
AB  - Difficult endotracheal intubation is a clinical challenge for anesthesiologists
      and other practitioners of airway management. The use of a tracheoscopic
      ventilation tube, a novel airway device, for endotracheal intubation during
      general anesthesia in two patients with difficult airways after unsuccessful
      direct laryngoscopy is presented.

PMID- 21723720
TI  - Microfluidic cell culture models for tissue engineering.
AB  - Microfluidic systems have emerged as revolutionary new platform technologies for
      a range of applications, from consumer products such as inkjet printer cartridges
      to lab-on-a-chip diagnostic systems. Recent developments have opened the door to
      a new set of opportunities for microfluidic systems, in the field of tissue and
      organ engineering. Advances in the design of physiologically relevant structures
      and networks, fabrication processes for biomaterials suitable for in vivo use,
      and techniques for scaling towards large, three-dimensional constructs, are
      converging towards therapeutic applications of microfluidic technologies in
      engineering complex tissues and organs. These advances herald a new generation of
      microfluidics-based approaches designed for specific tissue and organ
      applications, incorporating microvascular networks, structures for transport and
      filtration, and a three-dimensional microenvironment suitable for supporting
      phenotypic cell behavior, tissue function, and implantation and host integration.

PMID- 21723721
TI  - Structural insights into agonist-induced activation of G-protein-coupled
      receptors.
AB  - Recent years have seen tremendous breakthroughs in structure determination of G
      protein-coupled receptors (GPCRs). In 2011, two agonist-bound active-state
      structures of rhodopsin have been published. Together with structures of several
      rhodopsin activation intermediates and a wealth of biochemical and spectroscopic
      information, they provide a unique structural framework on which to understand
      GPCR activation. Here we use this framework to compare the recent crystal
      structures of the agonist-bound active states of the beta(2) adrenergic receptor
      (beta(2)AR) and the A(2A) adenosine receptor (A(2A)AR). While activation of these
      three GPCRs results in rearrangements of TM5 and TM6, the extent of this
      conformational change varies considerably. Displacements of the cytoplasmic side
      of TM6 ranges between 3 and 8A depending on whether selective stabilizers of the
      active conformation are used (i.e. a G-protein peptide in the case of rhodopsin
      or a conformationally selective nanobody in the case of the beta(2)AR) or not
      (A(2A)AR). The agonist-induced conformational changes in the ligand-binding
      pocket are largely receptor specific due to the different chemical nature of the
      agonists. However, several similarities can be observed, including a relocation
      of conserved residues W6.48 and F6.44 towards L5.51 and P5.50, and of I/L3.40
      away from P5.50. This transmission switch links agonist binding to the movement
      of TM5 and TM6 through the rearrangement of the TM3-TM5-TM6 interface, and
      possibly constitutes a common theme of GPCR activation.

PMID- 21723722
TI  - Using pretreated waste oyster and clam shells and microwave hydrothermal
      treatment to recover boron from concentrated wastewater.
AB  - Boron is an essential nutrient for animals and plants, but it can be harmful in
      excessive levels. In this study, three types of crushed shells (oyster, hard clam
      and freshwater clam) were pretreated and then reused as mineralizers to remove
      and recover the boron from concentrated wastewater by using the microwave
      hydrothermal method. Chemical and physical properties of raw and pretreated
      crushed shells were determined and compared using SEM, XRD, BET and WD-XRF.
      Effects of pretreatment method (heated or pyrolysis), particle sizes, initial
      boron concentrations, reaction times and shells dosages on boron recovery were
      investigated. The oyster shells pretreated by heat performed better than heated
      hard clam and freshwater clam shells, and the boron recovery efficiency reached
      around 95% within 10 min of reaction time. The experimental results indicate that
      the pretreated oyster shell is an effective mineralizer for removal and recovery
      of boron from concentrated wastewater.

PMID- 21723723
TI  - Effect of different supplements on bioprocessing of wheat straw by Phlebia
      brevispora: changes in its chemical composition, in vitro digestibility and
      nutritional properties.
AB  - Bioprocessing of wheat straw was carried out by Phlebia brevispora under solid
      state conditions. Effect of different supplements on lignocellulolytic enzymes
      production, degradation of straw cell wall fibers and its resultant effect on
      nutritional quality of wheat straw were studied. Ammonium chloride and malt
      extract were more effective in terms of ligninolysis and enhanced in vitro
      digestibility. The concentration of the selected supplements and the moisture
      content was worked out using response surface methodology in order to minimize
      the loss in total organic matter so as to selectively degrade lignin. The
      experiment was scaled up to batches of 200 g under optimized conditions and the
      degraded substrate was analyzed for its biochemical properties. P. brevispora
      degraded 290 g/kg of lignin and enhanced the in vitro digestibility from 150 to
      268 g/kg (78%). Crude protein, amino acids, total phenolic contents and
      antioxidant properties were significantly higher in degraded straw.

PMID- 21723724
TI  - Design-driven LO: the discovery of new ultra long acting dibasic beta2
      adrenoceptor agonists.
AB  - Starting with the molecular scaffold of the DA(2)/beta(2) dual agonist sibenadet
      (ViozanTM), a number of molecular changes were incorporated, which were designed
      to increase the potency and selectivity of the target molecule, and improve its
      pharmacokinetics. Through this process a novel, high potency, full beta(2)
      agonist with high selectivity and long duration capable of being dosed once daily
      has been discovered.

PMID- 21723725
TI  - Discovery of potent, soluble and orally active TRPV1 antagonists. Structure
      activity relationships of a series of isoxazoles.
AB  - Systematic optimisation of a poorly soluble lead series of isoxazole-3
      carboxamides was conducted. Substitution of the 4-position with specific polar
      functionality afforded the requisite balance of potency, solubility and
      physicochemical properties. Compound 21a was found to be efficacious in the rat
      Capsaicin Hargreaves assay following oral administration.

PMID- 21723726
TI  - Nobiletin metabolites: synthesis and inhibitory activity against matrix
      metalloproteinase-9 production.
AB  - A divergent synthesis of nobiletin metabolites was developed through highly
      oxygenated acetophenone derivative. We used commercially available methyl 3,4,5
      trimethoxybenzoate as a starting material for concise preparation of the key
      intermediate, 2'-hydroxy-3',4',5',6'-tetramethoxyacetophenone (I). These
      metabolites showed strong inhibitory activity against matrix metalloproteinase-9
      production in human lens epithelial cells.

PMID- 21723727
TI  - 176th ENMC International Workshop: diagnosis and treatment of coenzyme Q10
      deficiency.

PMID- 21723728
TI  - Clustered microcalcifications of intermediate concern detected on digital
      mammography: ultrasound assessment.
AB  - To report our experience with targeted-ultrasound in assessing 142 cases with
      clustered microcalcifications of intermediate concern detected on digital
      mammography. All cases had histopathologically-proven microcalcifications within
      the biopsied or surgical specimens. There were 30%[43/142] breast cancers and
      70%[99/142] benign lesions. Only 26%[37/142] of clustered microcalcifications
      were identified on targeted-ultrasound and other findings including negative
      study (n = 33), anechoic ducts or cysts (n = 70), dilated ducts with echogenic
      content (n = 13) and hypoechoic nodules (n = 26). There was no statistical
      difference of the frequency of negative ultrasound between benign and malignant
      microcalcifications (P = 0.071). However, only 7.1%[5/70] cases with anechoic
      ducts or cysts were proven to be breast cancer. The frequencies of depiction of
      dilated ducts with echogenic foci or hypoechoic nodules were significantly higher
      for malignant microcalcifications (P < 0.001). Ultrasound was significantly more
      sensitive for the identification of malignant cases but biopsy of clustered
      microcalcifications is still warranted when targeted-ultrasound revealed negative
      findings.

PMID- 21723729
TI  - Breast cancer treatment and work disability: patient perspectives.
AB  - PURPOSE: Most female breast cancer patients are forced to interrupt their
      professional activities during treatment. Qualitative research was carried out to
      assess women's experiences of being work disabled because of breast cancer.
      PATIENTS AND METHODS: In-depth interviews were analyzed to understand patient's
      experiences and to gain more insight in their perspectives on living with breast
      cancer. RESULTS: We identified a 'three-experience model': (1) disruption, with
      the feeling of irreparable loss, despair and no hope for the future; (2) episode,
      an unpleasant and inconvenient period, after which life continues as before;
      and/or (3) meaningful period, during which new life priorities' are set.
      CONCLUSION: The different experiences will require different types of support,
      especially concerning communication around disability and returning to work. Our
      findings highlight the need of an individual approach of the management of work
      disability for breast cancer patients.

PMID- 21723730
TI  - Regional white matter hyperintensities in normal aging, single domain amnestic
      mild cognitive impairment, and mild Alzheimer's disease.
AB  - Few studies have examined white matter hyperintensities (WMH) along the cognitive
      continuum between single-domain amnestic mild cognitive impairment (sd-aMCI) and
      Alzheimer's disease (AD). The aims of our study were to explore relationships
      between the extent and location of WMH and disease severity along the cognitive
      continuum and to determine whether differences in the distribution of WMH could
      be predictive of specific patterns of cognitive impairment. We compared cognitive
      function, vascular risk factors, and regional (frontal lobe, parieto-occipital
      [PO] lobe, temporal lobe, periventricular [PV] white matter and deep white
      matter) WMH volume in 37 patients with mild AD, 23 patients with sd-aMCI, and 24
      age-matched and education-matched normal controls. A quantitative volumetric
      method was applied to measure WMH burden. Total and regional WMH burdens, except
      for those in the temporal lobe, were significantly correlated with age (p<0.01).
      We found a trend toward increasing WMH volume with disease severity, higher in AD
      than in sd-aMCI and lowest in the controls. Total WMH volume was associated with
      the global cognitive test score. In multiple linear regression analysis, PV WMH
      volume, but not deep WMH volume, strongly predicted performances on the
      Controlled Oral Word Association test and the Color Word Stroop test after
      adjusting for important demographic variables. Only PO WMH volume was a
      significant predictor of a cognitive test score when frontal and temporal WMH
      volumes were simultaneously entered into the regression model. The extent and
      distribution of WMH, especially in the PV and PO regions, were associated with
      disease severity and reduced cognition.

PMID- 21723731
TI  - Chaperonins: two rings for folding.
AB  - Chaperonins are ubiquitous chaperones found in Eubacteria, eukaryotic organelles
      (group I), Archaea and the eukaryotic cytosol (group II). They all share a common
      structure and a basic functional mechanism. Although a large amount of
      information has been gathered for the simpler group I, much less is known about
      group II chaperonins. Recent crystallographic and electron microscopy structures
      have provided new insights into the mechanism of these chaperonins and revealed
      important differences between group I and II chaperonins, mainly in the molecular
      rearrangements that take place during the functional cycle. These differences are
      evident for the most complex chaperonin, the eukaryotic cytosolic CCT, which
      highlights the uniqueness of this important molecular machine.

PMID- 21723732
TI  - A comparison of tibiofemoral and patellofemoral alignment during a neutral and
      valgus single leg squat: an MRI study.
AB  - BACKGROUND: The etiology of anterior knee pain is not well understood. Recently,
      excessive hip adduction and internal rotation have been cited as possible
      factors. However, how these altered hip mechanics affect the patellofemoral joint
      is still unclear. OBJECTIVE: To compare the three-dimensional tibiofemoral and
      patellofemoral alignment between a neutral squat and one performed with increased
      hip adduction and internal rotation. We aimed to examine the relationships
      between the three-dimensional tibiofemoral and patellofemoral alignment during a
      neutral and valgus squat. Finally, we aimed to determine the relationship between
      two-dimensional and three-dimensional measures of patellofemoral alignment.
      METHODS: 10 healthy subjects were recruited for this study. Knee and patellar
      kinematics in a neutral squat and one performed with hip adduction and internal
      rotation were measured using a open, upright, magnetic resonance imaging unit.
      Both single leg squats were performed at 30 degrees  of knee flexion. RESULTS:
      There was a significant correlation between knee external rotation and lateral
      patellar translation, and between knee abduction and lateral patellar
      translation. Moderate relationships were found between the 2D and 3D measures but
      these were not statistically significant. CONCLUSION: The valgus squat resulted
      in greater knee external rotation in all subjects. Although mean patellar
      mechanics were not different in the valgus squat, lateral patellar translation
      increased as knee external rotation increased. Lastly, 2D measures of
      patellofemoral alignment only provide moderately fair surrogates for 3D measures.

PMID- 21723733
TI  - Human HDAC isoform selectivity achieved via exploitation of the acetate release
      channel with structurally unique small molecule inhibitors.
AB  - Herein we report the discovery of a family of novel yet simple, amino-acid
      derived class I HDAC inhibitors that demonstrate isoform selectivity via access
      to the internal acetate release channel. Isoform selectivity criteria is
      discussed on the basis of X-ray crystallography and molecular modeling of these
      novel inhibitors bound to HDAC8, potentially revealing insights into the
      mechanism of enzymatic function through novel structural features revealed at the
      atomic level.

PMID- 21723734
TI  - Synthesis and antimalarial activity of new heterocyclic hybrids based on
      chloroquine and thiazolidinone scaffolds.
AB  - A series of new 21 chloroquine heterocyclic hybrids containing either benzylamino
      fragment or N-(aminoalkyl)thiazolidin-4-one moiety were synthesized and screened
      for their antimalarial activity against chloroquine (CQ)-sensitive 3D7 and
      multidrug-resistance Dd2 strains of Plasmodium falciparum. Although no compounds
      more active than CQ against 3D7 was found; against Dd2 strain, six compounds,
      four of them with benzylamino fragment, showed an excellent activity, up to 3
      fold more active than CQ. Non specific cytotoxicity on J774 macrophages was
      observed in some compounds whereas only two of them showed liver toxicity on
      HepG2 cells. In addition, all active compounds inhibited the ferriprotoporphyrin
      IX biocrystalization process in concentrations around to CQ. In vivo preliminary
      results have shown that at least two compounds are as active as CQ against
      Plasmodium berghei ANKA.

PMID- 21723735
TI  - Synthesis of some new [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and
      [1,2,4]triazolo[3,4-b][1,3,4] thiadiazoles starting from 5-nitro-2-furoic acid
      and evaluation of their antimicrobial activity.
AB  - New series of fused 1,2,4-triazoles such as, 6-(aryl)-3-(5-nitrofuran-2-yl)-5,6
      dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 4-8, 6-(alkyl/aryl amino)-3-(5
      nitrofuran-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 9-13 and 6-(4
      substituted phenyl)-3-(5-nitrofuran-2-yl)-7H-[1,2,4]triazolo[3,4
      b][1,3,4]thiadiazines 14-18 have been synthesized via the reaction of 4-amino-5
      (5-nitrofuran-2-yl)-4H-1,2,4-triazole-3-thiol 3 with various reagents such as
      hetero aromatic aldehydes, alkyl/aryl isothiocyanates and 4-substituted phenacyl
      bromides, respectively. The structures of the newly synthesized compounds have
      been confirmed on the basis of elemental analysis and spectral studies. The newly
      synthesized triazolo derivatives have been investigated for their in vitro
      antibacterial activity. Most of the tested compounds showed interesting
      antibacterial activity against Staphylococcus aureus. Furthermore, the most
      potent antibacterial compounds 11-13 were evaluated for their in vitro cytotoxic
      activity against human cancer cell lines. It was found that compounds 11 and 13
      showed higher cytotoxicity against Hep-G2 cell line as compared to standard.

PMID- 21723736
TI  - Pressure and scattering regime influence on the EDS profile resolution at a
      composite interface in environmental SEM.
AB  - Gas impact on the EDS profile resolution at the interface of composite interface
      resin/Al was investigated with two gaseous environments: helium and water vapor.
      Two main components of the global profile at the interface were investigated: the
      contrast of the profile and the spatial resolution. A complementary approach was
      developed by comparing gas nature impact versus the pressure and versus the
      scattering regime. The results show that the unscattered electron beam mainly
      governs EDS profile spatial resolution as long as the scattering regime is single
      or oligo scattering. Then for plural scattering, spatial resolution is
      dramatically degraded. In addition, the contrast is degraded since a gas is
      introduced, whatever the gas, the pressure and so the scattering regime. This
      approach would enable to better understand the respective contributions of the
      unscattered beam and the skirt and the influence of the gases nature on them.

PMID- 21723737
TI  - Structural and elemental analysis of iron and indium doped zinc oxide by
      spectroscopic imaging in Cs-corrected STEM.
AB  - ZnO with additions of Fe2O3 or In2O3 shows characteristic inversion domain
      structures. ZnO domains are separated by two types of inversion domain boundaries
      (IDBs): basal b-IDBs parallel to (0001) planes, and complementary pairs of three
      possible variants of pyramidal p-IDBs parallel to {2115} lattice planes. The
      structure and composition of IDBs were investigated in a sophisticated aberration
      corrected scanning transmission electron microscope (probe-corrected TEM/STEM).
      It is shown that Fe and In additions are essentially located in monolayers within
      the IDBs, and EELS electron spectroscopic imaging (ESI) as well as EDS
      spectroscopic imaging by X-rays (SIX) are capable of rapidly mapping the element
      distribution. With solid solubility of trivalent dopant species well below 1at.%
      within ZnO domains, the lateral spacings of b-IDBs are inversely proportional to
      the dopant concentration. Quantification of data acquired by ESI and SIX from
      well defined sample regions in STEM both confirm the assumption of one full
      monolayer of dopants per IDB. Atom columns of cations are well resolved in HAADF
      STEM imaging; experimental contrast intensities are approximately proportional to
      Z1.6. Furthermore, annular bright-field (ABF)-STEM imaging is capable of
      resolving oxygen columns even in thick sample regions, thus providing highly
      localized information on atom positions and lattice distortions, and enables the
      construction of more reliable structure models of IDBs in doped ZnO.

PMID- 21723738
TI  - Study of K-line radiation of thick titanium produced in collisions of keV
      electrons.
AB  - The characteristic K-line yields Y(E0) of a pure thick titanium (Z=22) element
      target are measured for 8-18 keV electron impact and compared with the simulation
      calculations using PENELOPE code. A fair agreement between experiment and
      simulation results is found within the existing experimental uncertainty of
      measurements. The ratio F of indirectly produced characteristic Ti K X-ray yield
      to its total (directly+indirectly) yield is determined by employing an
      approximate analytical formulation of Hanson and Cowan (Hanson, H.P., Cowan,
      D.J., 1961. Phys. Rev. 124, 22-26). It is found that F changes strongly with
      impact energy E0 for normal angle of incidence in contrast to a mild change
      predicted by the simulation calculations. Furthermore, experimental and
      simulation results for peak to effective continuum ratio R of Ti K-line are
      compared and discussed for the energy range of impact of the present
      investigation.

PMID- 21723739
TI  - Identification and characterization of two plasma membrane aquaporins in durum
      wheat (Triticum turgidum L. subsp. durum) and their role in abiotic stress
      tolerance.
AB  - Plant plasma membrane intrinsic proteins (PIP) cluster in two phylogenetic
      groups, PIP1 and PIP2 that have different water channel activities when expressed
      in Xenopus oocytes. PIP2s induce a marked increase of the membrane osmotic water
      permeability coefficient (P(f)), whereas PIP1s are generally inactive. Here we
      report the cloning of two durum wheat (Triticum turgidum L. subsp. durum) cDNAs
      encoding TdPIP1;1 and TdPIP2;1 belonging to the PIP1 and PIP2 subfamilies,
      respectively. Contrary to TdPIP1;1, expression of TdPIP2;1 in Xenopus oocytes
      resulted in an increase in P(f) compared to water-injected oocytes. Co-expression
      of the non-functional TdPIP1;1 and the functional TdPIP2;1 lead to a significant
      increase in P(f) compared with oocytes expressing TdPIP2;1 alone. A truncated
      form of TdPIP2;1, tdpip2;1, missing the first two transmembrane domains, had no
      water channel activity. Nonetheless, its co-expression with the functional
      TdPIP2;1 partially inhibits the P(f) and disrupt the activities of plant
      aquaporins. In contrast to the approach developed in Xenopus oocytes, phenotypic
      analyses of transgenic tobacco plants expressing TdPIP1;1 or TdPIP2;1 generated a
      tolerance phenotype towards osmotic and salinity stress. TdPIP1;1 and TdPIP2;1
      are differentially regulated in roots and leaves in the salt-tolerant wheat
      variety when challenged with salt stress and abscisic acid. Confocal microscopy
      analysis of tobacco roots expressing TdPIP1;1 and TdPIP2;1 fused to the green
      fluorescent protein showed that the proteins were localized at the plasma
      membrane.

PMID- 21723741
TI  - Pharmacokinetics of IgG1 monoclonal antibodies produced in humanized Pichia
      pastoris with specific glycoforms: a comparative study with CHO produced
      materials.
AB  - A glycoengineered Pichia pastoris host was used to produce an IgG1 with either
      afucosylated N-glycosylation (afucosylated biantennary complex) or without N
      glycosylation (N297A) while a wild type P. pastoris host was used to produce an
      IgG1 containing fungal-type N- and O-linked glycosylation. The PK properties of
      these antibodies were compared to a commercial IgG1 produced in CHO cells
      following intravenous administration in wild type C57B6, FcgammaR-/- or hFcRn
      transgenic mice. MAbs produced in glycoengineered yeast exhibited similar PK
      properties in wild type mice or FcgammaR-/- mice with respect to clearance (CL),
      volume of distribution at steady-state (Vss) and half-life (t(1/2)) to that
      produced in mammalian (CHO) cells, while the mAb produced in wild type yeast
      exhibited ~2-3-fold faster CL, which might be due to the high mannose content
      interacting with mannose receptors. Furthermore, in vitro binding affinity to
      human FcRn or mouse FcRn was similar between the reference mAb and mAbs produced
      in humanized yeast, and the glycovariants produced in humanized yeast exhibited
      similar PK patterns in human FcRn transgenic mice and in wild type mice. These
      results suggest the potential application of P. pastoris as a production platform
      for clinically viable mAbs.

PMID- 21723740
TI  - The innate immune system in transplantation.
AB  - The vertebrate innate immune system consists of inflammatory cells and soluble
      mediators that comprise the first line of defense against microbial infection
      and, importantly, trigger antigen-specific T and B cell responses that lead to
      lasting immunity. The molecular mechanisms responsible for microbial non-self
      recognition by the innate immune system have been elucidated for a large number
      of pathogens. How the innate immune system recognizes non-microbial non-self,
      such as organ transplants, is less clear. In this review, we approach this
      question by describing the principal mechanisms of non-self, or 'damaged' self,
      recognition by the innate immune system (pattern recognition receptors, the
      missing self theory, and the danger hypothesis) and discussing whether and how
      these mechanisms apply to allograft rejection.

PMID- 21723742
TI  - Increased use of intrauterine contraception in California, 1997 to 2007.
AB  - BACKGROUND: Modern intrauterine contraception (IUC) is safe and highly effective,
      but is used by fewer than 4% of women in the United States. Once recommended only
      for women with at least one child, it is now recommended for most women
      regardless of parity or age. METHODS: This study used data representative of
      California women from 10 years of the California Women's Health Survey (1997
      2007) to describe how IUC users differ from women using other contraceptives, and
      assess changes in IUC users' characteristics over time. FINDINGS: Overall 4.9% of
      women in California used IUC. Multivariable logistic regression modeling showed
      IUC users were more likely to be born outside the United States (odds ratio [OR],
      1.7), have a college degree (OR, 1.5) or postgraduate degree (OR, 2.2), and be
      married (OR, 2.6) or in an unmarried partnership (OR, 2.4). IUC users were 71%
      less likely to be nulliparous (OR, 0.29). Use of IUC almost doubled over the
      study period from 4.0% to 7.2%, and this growth was accompanied by significant
      changes in user characteristics: Young women, women born in the United States,
      women without a college degree, and Asian women experienced the greatest
      increases. IUC use among nulliparous women did not increase. CONCLUSION: IUC use
      in California is higher than the national average and growing. We found higher
      IUC use among ever-married women and foreign-born women, and disproportionately
      low use among nulliparous women. Efforts to inform women of IUC's high
      effectiveness and safety, as well as efforts to ensure that health care providers
      have the necessary clinical skills, are timely and important.

PMID- 21723743
TI  - Do ambivalent women have an unmet need for family planning? A longitudinal study
      from Bali, Indonesia.
AB  - INTRODUCTION: Fertility intentions often can predict contraceptive demand and
      fertility outcomes. Little is known about women reporting ambivalent fertility
      intentions, who are usually classified as having an unmet need for contraception.
      This study's objectives were to determine 1) which fertility intention group
      ambivalent women more closely resemble and 2) whether ambivalent women seem to
      have an unmet contraceptive need. METHODS: We analyzed longitudinal data from
      1,018 married Balinese women aged 15 to 45, of whom 33% desired more children,
      52% wanted no more, and 14% were ambivalent. Ambivalent women were compared with
      those with definitive intentions using bivariate analyses. Regression analysis
      was used to determine the predictors of birth avoidance. RESULTS: Although
      ambivalent women were significantly older, and had less education and more
      children than women who wanted more children, ambivalent women were more similar
      in their contraceptive use to those who wanted more children than those who
      wanted no more. However, in terms of birth outcomes, ambivalent women resembled
      more the women who intended to avoid childbearing: After 4 years, 33% of
      ambivalent women had another birth compared with 29% of women who wanted no more
      and 57% of women who desired more children. Contraceptive use at baseline did not
      predict ambivalent women's fertility outcomes, unlike the other groups.
      CONCLUSION: Despite their relatively low rates of contraceptive use at baseline,
      ambivalent women generally avoided giving birth during the study period. This
      suggests that ambivalent women may not have a high unmet need for family
      planning.

PMID- 21723744
TI  - Role of perfusion imaging in differentiating multifocal vasospasm-related
      ischemia versus thromboembolic stroke in a setting of cocaine abuse.
AB  - Cerebrovascular complications related to cocaine abuse are reaching epidemic
      proportions. Contemporary treatments for acute stroke have made it essential to
      gather all possible diagnostic information before proceeding with intervention.
      We describe a cocaine abuser who presented with acute right sided neurological
      deficits and deteriorating mental status. An MRI demonstrated right sided acute
      and chronic infarcts in the border zones of the right anterior cerebral arteries
      (ACA) and middle cerebral arteries (MCAs). Subsequent CT angiography (CTA)/CT
      perfusion (CTP) identified multifocal cerebral vasospasm of the bilateral ACAs
      and MCAs, preserved cerebral blood volume (CBV) and decreased cerebral blood flow
      (CBF) in bilateral frontoparietal regions. Early diagnosis of multifocal
      vasospasm related ischemia directed appropriate therapy and excluded thrombolytic
      intervention. After 3 weeks, patient's presenting symptoms gradually resolved. We
      report a unique case of cocaine induced multifocal vasospasm exhibiting late (>3
      weeks) reversibility of focal neurological deficits. Furthermore, we illustrate
      the benefits of CTA/CTP imaging in the setting of cocaine abuse, differentiating
      multifocal vasospasm induced hypoperfusion/ischemia from focal thromboembolic
      ischemia/infarct and allowing for appropriate medical management in the crucial
      hyperacute setting.

PMID- 21723745
TI  - Transthoracic echocardiography: training options for practicing physicians.

PMID- 21723746
TI  - Predictive value of the additive and logistic EuroSCOREs in patients undergoing
      aortic valve replacement.
AB  - OBJECTIVES: The purpose of this study was to evaluate the accuracy of the
      additive and logistic EuroSCOREs in predicting the operative mortality in
      patients undergoing aortic valve replacement (AVR) with or without coronary
      artery bypass graft (CABG) surgery. DESIGN: This was a retrospective analysis of
      prospectively collected data. SETTING: This was a single-center study performed
      in an educational hospital. PARTICIPANTS: All patients (n = 1,885) who underwent
      AVR with (n = 813) or without (n = 1,072) CABG surgery between 1998 and 2007.
      INTERVENTIONS: AVR with or without CABG surgery. MEASUREMENTS AND MAIN RESULTS:
      Variable life-adjusted display curves were constructed to compare the observed
      operative mortality with the additive and logistic EuroSCOREs. The receiver
      operating characteristics (ROC) curve was used to determine the discriminatory
      power of the additive and logistic EuroSCOREs. Calibration between the predicted
      and the observed operative mortality was checked by comparing the predicted
      probability of the mortality with the additive and logistic EuroSCORE. In the
      isolated AVR group, the additive EuroSCORE was 5.8% predicted mortality and the
      logistic EuroSCORE was 7.2%, whereas the observed operative mortality was 3.2%.
      In the AVR with CABG surgery group, the additive EuroSCORE was 7.2% and the
      logistic EuroSCORE was 8.8%, whereas the observed operative mortality was 5.3%.
      ROC curve analyses showed a high discriminatory power for both EuroSCOREs in both
      patient groups. CONCLUSIONS: Although the additive and the logistic EuroSCOREs
      had good discriminatory power, they were not able to predict the actual operative
      mortality accurately. Both EuroSCOREs overestimated the operative mortality,
      especially in low-risk patients.

PMID- 21723747
TI  - Advanced glycation end products in diabetic cardiomyopathy: an alternative
      hypothesis.

PMID- 21723748
TI  - On the role of attention in generating explicit awareness of contingent
      relations: evidence from spatial priming.
AB  - In a series of four experiments, we examine the hypothesis that selective
      attention is crucial for the generation of conscious knowledge of contingency
      information. We investigated this question using a spatial priming task in which
      participants were required to localize a target letter in a probe display. In
      Experiment 1, participants kept track of the frequency with which the predictive
      letter in the prime appeared in various locations. This manipulation had a
      negligible impact on contingency awareness. Subsequent experiments requiring
      participants to attend to features (color, location) of the predictive letter
      increased contingency awareness somewhat, but there remained a large proportion
      of individuals who remained unaware of the strong contingency. Together the
      results of our experiments suggest that the construct of attention does not fully
      capture the processes that lead to contingency awareness, and suggest a critical
      role for bottom-up feature integration in explicit contingency learning.

PMID- 21723749
TI  - Magnetic resonance imaging study of glenohumeral relationships between genders.
AB  - BACKGROUND: During glenohumeral arthroplasty, not only should the dimensions of
      the prosthesis match the normal anatomy but also the relationship of the humeral
      head-greater tuberosity and humeral head inclination should be replicated to
      avoid muscular dysfunction. To date there is no evidence whether fit could be
      optimized with gender-specific prostheses. MATERIALS AND METHODS: Magnetic
      resonance (MR) arthrography imaging was used to evaluate 81 proximal humeral
      scans for 5 different anatomic parameters. The study group included 41 men and 40
      women, aged 20 to 62 years. Anatomic parameters, including the humeral head
      height, humeral head width, humeral head-greater tuberosity distance, humeral
      head inclination, and glenoid version were measured using Horizon Rad Station
      11.0 to evaluate the MR imaging. RESULTS: The humeral head height, width, and
      distance to the greater tuberosity were significantly different in size between
      genders. However, none of the anatomic relationships were different. The humeral
      head-greater tuberosity distance significantly correlated with the humeral head
      inclination in both men (r = 0.338; P < .05) and women (r = 0.448; P < .005).
      CONCLUSION: We conclude that there are no significant differences in glenohumeral
      relationships between genders.

PMID- 21723750
TI  - Effect of WF10 (immunokine) on diabetic foot ulcer therapy: a double-blind,
      randomized, placebo-controlled trial.
AB  - This randomized controlled trial was undertaken to evaluate the effect of WF10
      (Immunokine) as an adjunct to the standard treatment of diabetic foot ulcer. A
      total of 40 participants were randomized into 2 groups of 20. One group underwent
      standard therapy combined with infusions of WF10, and 1 underwent standard
      therapy combined with placebo. The wound severity scores, which vary with the
      severity of infection and inflammation, necrotic and granulation tissues, and
      wound depth and area, were assessed weekly for 9 weeks. Before treatment, the
      wound severity scores were not significantly different statistically between the
      2 groups (13.7 +/- 2.8 and 12.9 +/- 3.2). After 9 weeks, the WF10 group had a
      statistically significant decreased wound severity score compared with that of
      the placebo group (1.8 +/- 1.9 versus 4.4 +/- 5.3, respectively, p < .05).
      Subgroup analyses comparing the WF10 and placebo groups showed statistically
      significant decreases of infection and inflammation (0.0 +/- 0.0 versus 0.8 +/-
      0.9, respectively, p < .01), necrotic tissue (0.0 +/- 0.0 versus 0.8 +/- 1.1,
      respectively, p < .01), and an increase of the amount of granulation tissue (0.1
      +/- 0.3 versus 0.8 +/- 1.2, respectively, p < .05). The wound depth and wound
      area also decreased more in the WF10 group; however, these decreases were not
      statistically significant. No severe adverse events were observed throughout the
      observation period. We concluded that the addition of WF10 to standard wound care
      statistically significantly reduced the wound severity score, infection and
      inflammation, and necrotic tissue and enhanced the formation of granulation
      tissue.

PMID- 21723751
TI  - Treadway's lasting contribution to surgical residency training.

PMID- 21723752
TI  - Probe ablation as salvage therapy for renal tumors in von Hippel-Lindau patients:
      the Cleveland Clinic experience with 3 years follow-up.
AB  - BACKGROUND: To evaluate the efficacy and safety of probe ablative therapy as
      salvage treatment for renal tumor in von Hippel-Lindau (VHL) patients after
      previous partial nephrectomy (PN). METHODS: Medical records of VHL patients
      undergoing probe ablative treatment for renal tumors from March 2003 to January
      2010 at our institution were retrospectively analyzed. RESULTS: Fourteen VHL
      patients who were submitted to salvage probe ablative therapy were included in
      the analysis. Twelve patients (85%) had a solitary kidney. Overall, 33 tumors
      were ablated by either percutaneous cryoablation (P-Cryo) (n of procedures = 13),
      radiofrequency ablation (RFA) (n = 14), and laparoscopic cryoablation (L-Cryo) (n
      = 3). Average maximal renal tumor diameter was 2.6 +/- 1 cm. Average ablation
      time was 18.3 +/- 2.1 minutes for P-Cryo, 36.7 +/- 17 minutes for RFA, and 17.3
      +/- 4 minutes for L-Cryo. All procedures were successfully completed without
      transfusions and intraoperative complications. No early postoperative
      complications were recorded. Postoperative decline in renal function was minimal
      and not clinically significant. With a mean follow-up of 37.6 months (range 12
      82), 4 patients had a suspicious recurrence on computed tomography/magnetic
      resonance imaging (CT/MRI) scan and in 3 of them a re-ablation was performed.
      Actuarial overall and cancer-specific survivals were 92% and 100%, respectively.
      CONCLUSIONS: Probe ablative therapy seems to represent a suitable treatment
      option for VHL patients with a previous history of PN as it offers a repeatable
      operation, with a high technical success rate and causing minor changes in renal
      function.

PMID- 21723753
TI  - Molecular markers of kidney injury.
AB  - Renal dysfunction is common in urologic patients, especially in those undergoing
      nephrectomy for renal cancer. Partial nephrectomy better preserves renal function
      than radical nephrectomy, but is associated with acute kidney injury related to
      loss of nephrons and ischemic injury. Ischemic injury may not be reliably
      assessed using common clinical parameters, such as serum creatinine and urine
      output, which may delay detection of clinically-significant kidney damage.
      Molecular markers, such as cystatin C, neutrophil gelatinase-associated lipocalin
      (NGAL), IL-18 and kidney injury molecule-1 (KIM-1), better quantify the extent of
      acute ischemic and/or tubular injury than other currently available tools. The
      use of these and/or other markers may facilitate research to improve outcomes
      following partial nephrectomy. 

PMID- 21723754
TI  - Carotid rete mirabile and pseudoxanthoma elasticum: an accidental association?
AB  - We report the case of a young female patient with a transient amaurosis due to a
      carotid rete mirabile (CRM), a rare congenital carotid malformation, and
      pseudoxanthoma elasticum (PXE), an inherited autosomal recessive systemic
      metabolic disorder characterised by fragmentation and mineralisation of elastic
      fibres in connective tissues (skin, eyes) and the vascular system. CRM is a rare
      form of intracranial carotid malformation whose association with PXE (6 cases at
      present) would appear not to be accidental. This observation suggests a new link
      between congenital arterial remodelling and the PXE.

PMID- 21723755
TI  - Hypercortisolism affects glomerular and tubular function in dogs.
AB  - Renal function was assessed in 25 dogs with Cushing's syndrome and in 12 healthy
      controls. Routine renal parameters and glomerular filtration rate (GFR) were
      measured and urinary biomarkers such as urinary albumin (uALB), urinary
      immunoglobulin G (uIgG), and urinary retinol-binding protein (uRBP) were assessed
      by ELISA. Urinary N-acetyl-beta-D-glucosaminidase activity (uNAG) was determined
      colorimetrically. All urinary markers were indexed to urinary creatinine
      concentration (c). Plasma exo- (Cl(exo)) and endo-iohexol (Cl(endo)) clearance
      were used to measure GFR. Based on a Mann-Whitney U test, urea and Cl(exo) did
      not differ, sCr was significantly lower, and UPC, uALB/c, uIgG/c, uRBP/c, uNAG/c
      and Cl(endo) were higher in the dogs with Cushing's syndrome when compared with
      controls. The findings indicate that glomerular and tubular function are both
      altered in dogs with Cushing's syndrome. Further longitudinal studies will be
      required to elucidate the pathogenesis of the changes in GFR.

PMID- 21723756
TI  - Back to basics: stem cells and veterinary medicine.

PMID- 21723757
TI  - Does the taking of biopsies affect the metastatic potential of tumours? A
      systematic review of reports on veterinary and human cases and animal models.
AB  - Clinicians and pathologists are sporadically asked by owners whether the taking
      of tumour biopsies may affect the behaviour of the tumour, including its
      potential to metastasise. Unfortunately, systematic studies on this subject are
      unavailable in veterinary medicine, and the aim of this study was to estimate the
      risk of adverse effects of biopsy taking on tumour progression in animals. A
      systematic review of veterinary and human case reports and clinical studies as
      well as experimental animal models of biopsy-induced tumour metastasis was
      undertaken. There were only two veterinary case reports of needle tract
      metastases (NTM) following the taking of needle biopsies from urogenital and
      pulmonary tumours. Seventeen experimental studies found a high incidence of NTM
      but only a rat osteosarcoma and a hamster squamous carcinoma model showed an
      increased incidence of distant or regional metastases after incision or excision
      biopsy. In human medicine, the occurrence of NTM has been reported after the
      taking of biopsies from mesotheliomas (15%), melanomas (11%) and gall bladder
      tumours (11%), liver metastases of colon carcinomas (4%) and mammary carcinomas
      (4%) but an incidence of only <1% for all other tumours. Circulating tumour cells
      increased immediately after the taking of biopsies from human squamous cell,
      prostate, breast and hepatocellular carcinomas. Although no increased risk of
      biopsy-induced distant metastasis has been reported for any type of tumour, this
      is inconclusive due to a lack of non-biopsied control groups in human studies.
      Reports of biopsy-induced metastasis in animal tumours indicate that the taking
      of transcutaneous biopsies from urogenital tumours may be associated with a risk
      of NTM. However, there is no evidence of a general increase in risk of distant
      metastases in any tumour type in people or animals. The overall risk therefore
      appears to be negligible when compared to the valuable information obtained from
      biopsies in veterinary practice.

PMID- 21723758
TI  - Comparison of 3 instruments to measure muscle strength in children: A prospective
      study.
AB  - AIM: To establish which instrument is the most valid and reliable measure of
      muscle strength in children aged 4-11 years and can improve the diagnostic
      procedure in children with suspected myopathy to spare more of them from muscle
      biopsy. METHODS: In a prospective study over a 2 year period, 22 patients aged 4
      11 years were recruited. They had all been referred to our specialist centre on
      the suspicion of myopathy. Hand-held dynamometry, the Jamar dynamometer and a new
      Motor Performance Test were administered before muscle biopsy. Validity was
      assessed by the power to discriminate between patients with and without myopathy
      using logistic regression analysis and receiver operating characteristic (ROC)
      analysis. The area under the ROC curve (AUC) was calculated as a measure of the
      diagnostic power. RESULTS: Comparison of the three instruments showed that the
      Motor Performance Test had the highest validity. Hand-held dynamometry generally
      had lower validity and showed wide variation in the 11 muscle groups. The Jamar
      dynamometer had very low validity in early stage myopathy. CONCLUSION: The Motor
      Performance Test was the most valid and reliable instrument to indicate the
      presence of myopathy in children. This objective, non-invasive and child-friendly
      instrument can improve the diagnostic procedure and exclude more children without
      myopathy from muscle biopsy.

PMID- 21723760
TI  - Plexiform leiomyoma of the esophagus: a complex radiographic, pathologic and
      endoscopic diagnosis.
AB  - Radiographic identification of an abnormal lesion in the esophagus routinely
      occurs during workup of patients with symptomatic dysphagia. Leiomyoma is the
      most common benign finding; however, plexiform leiomyoma, a distinctive but rare
      variant, follows an unusual pattern of growth which can be a challenging surgical
      resection. A review of indexed literature identified a single previous report. We
      contribute a second case of plexiform leiomyoma with a discussion of the
      clinical, radiographic, and pathologic characteristics, as well as the
      differential diagnosis for plexiform lesions.

PMID- 21723761
TI  - Fracture burden in relation to low bone mineral density and FRAX((r))
      probability.
AB  - Although the risk of fracture increases exponentially with declining bone mineral
      density, most fragility fractures have been shown to occur in individuals who do
      not meet the conventional densitometric definition for osteoporosis. The World
      Health Organization fracture risk assessment tool (FRAX((r))) estimates
      individual 10-yr major osteoporotic and hip fracture probabilities. Intervention
      criteria based on risk assessment have been proposed by several groups, including
      the National Osteoporosis Foundation (NOF). We determined the relationship
      between 10-yr fracture probability and subsequent fracture burden in 36,730 women
      and 2873 men aged 50yr and older. Using a major fracture probability cutoff of
      20%, 29.4% of major osteoporotic fractures were identified in women and 4.9% in
      men. Based on a hip fracture probability cutoff of 3%, 54.1% of major
      osteoporotic fractures were detected in women and 53.4% in men. Using all NOF
      criteria, 65.9% of major osteoporotic fractures were detected in women and 69.3%
      in men. We conclude that men and women with FRAX probabilities below the high
      risk NOF cutoffs have a high burden of major osteoporotic fractures. Strategies
      to enhance risk stratification in this group should be developed through
      international collaborations.

PMID- 21723762
TI  - Early changes in body composition after cessation of growth hormone therapy in
      childhood-onset growth hormone deficiency.
AB  - At final height, somatic maturity has not been reached yet. We investigated bone
      and body composition in patients, who completed pediatric growth hormone (GH)
      treatment at final height. After a mean period of 0.55 +/- 0.17 yr off GH
      treatment 90 (66 m/24 f) childhood-onset growth hormone deficiency (GHD) patients
      were reinvestigated for GHD by insulin tolerance testing at a mean age of 17.52
      +/- 1.50 yr. Thirty-seven (25 m/12 f) patients remained GH deficient (persistent
      GHD). Bone and body composition were measured using peripheral quantitative
      computed tomography of the nondominant forearm. Bone mineral density (BMD) was
      within normal limits. Total cross-sectional bone area Z-score (0.64 +/- 1.3) was
      significantly higher as a result of an enlarged medullary cavity Z-score (1.12 +/
      1.2) leading to reduction of cortical thickness Z-score (-1.21 +/- 1.0).
      Patients with persistent GHD had a significantly higher fat mass (13.3 +/- 8.7
      and 6.8 +/- 4.6 cm(2), p<0.05), which was more pronounced in multiple pituitary
      hormone deficiency patients. Shortly after cessation of GH treatment in patients
      treated for childhood-onset GHD age adequate normal BMD and enlarged diaphysis
      was detectable. Patients with persistent GHD status had a significant higher fat
      mass.

PMID- 21723763
TI  - Vertebral fractures and the misclassification of osteoporosis in men with
      prostate cancer.
AB  - Androgen deprivation therapy (ADT) has become the cornerstone of treatment for
      both advanced and nonmetastatic prostate cancer. The presence of a nontraumatic
      vertebral fracture (VF) identifies a patient who has clinical osteoporosis.
      Vertebral fracture analysis (VFA), a dual-energy X-ray absorptiometry (DXA)-based
      technology identifies VFs in conjunction with a standard bone mineral density
      (BMD) examination. The objective of this study was to determine if VFA would
      increase the diagnosis of osteoporosis in men with prostate cancer on ADT. One
      hundred sixteen men aged >= 60yrs with nonmetastatic prostate cancer receiving
      ADT for >= 6mos underwent DXA of the spine, hip, and 1/3 distal radius, VFA, and
      conventional vertebral X-rays. Approximately 40% of the men had clinically
      defined osteoporosis. The use of conventional DXA criteria (spine and hip) alone
      resulted in the misdiagnosis of approx 75% of patients. VFA and addition of the
      1/3 distal radius site performed by DXA both increased the rate of diagnosis and
      reduced the misclassification of osteoporosis in men with prostate cancer,
      compared with conventional DXA criteria alone. Analysis indicated that VFA
      assessment of mild, moderate, and severe fractures from all readable vertebrae
      (T5-L4) had a kappa statistic, sensitivity, and specificity of 0.92, 100%, and
      95%, respectively, with semiquantitative radiography. Men with prostate cancer on
      ADT should be screened for osteoporosis at the initiation of therapy, and
      evaluation should include DXA of the 1/3 distal radius in addition to the spine
      and hip, as well as evaluation for VFs.

PMID- 21723764
TI  - Volumetric quantitative computed tomography measurement precision for volumes and
      densities of tarsal and metatarsal bones.
AB  - Diabetic foot diseases, such as ulcerations, infections, and neuropathic
      (Charcot's) arthropathy, are major complications of diabetes mellitus (DM) and
      peripheral neuropathy (PN) and may cause osteolysis (bone loss) in foot bones.
      The purposes of our study were to make computed tomography (CT) measurements of
      foot-bone volumes and densities and to determine measurement precision (percent
      coefficients of variation for root-mean-square standard deviations) and least
      significant changes (LSCs) in these percentages that could be considered
      biologically real with 95% confidence. Volumetric quantitative CT scans were
      performed and repeated on 10 young healthy subjects and 13 subjects with DM and
      PN. Two raters used the original- and repeat-scan data sets to make measurements
      of volumes and bone mineral densities (BMDs) of the tarsal and metatarsal bones
      of the 2 feet (24 bones). Precisions for the bones ranged from 0.1% to 0.9% for
      volume measurements and from 0.6% to 1.9% for BMD measurements. The LSCs ranged
      from 0.4% to 2.5% for volume measurements and from 1.5% to 5.4% for BMD
      measurements. Volumetric quantitative CT provides precise measurements of volume
      and BMD for metatarsal and tarsal bones, where diabetic foot diseases commonly
      occur.

PMID- 21723765
TI  - Peripheral quantitative computed tomography: optimization of reproducibility
      measures of bone density, geometry, and strength at the radius and tibia.
AB  - The aim of this study was to determine the reproducibility for in vivo
      measurements at the radius and tibia for trabecular and cortical parameters, bone
      geometry, and bone strength indices with the peripheral quantitative computed
      tomography (pQCT) XCT 3000. We performed 3 repeated scans within 2mo at the
      radius (N=18) and tibia (N=16) on healthy, premenopausal women, aged 22-35 yrs
      and report precision measures including %coefficient of variation (%CV) and least
      significant changes (LSCs). For the radius, we studied 2 sections (4% and 33% of
      total length) and for the tibia, 3 sections (4%, 38%, and 66% of total length).
      Reproducibility for radius at 33% and tibia at every site was good (%CV ranged
      from 0.02% to 2.19%). The precision error for the distal 4% radius was, however,
      higher. The reproducibility at the distal radius improved when we considered only
      the scans with a change of +/- 10mm(2) in the radius total area at this site (%CV
      from 0.87% to 2.25%). This study showed that, when follow-up measurements are
      carefully obtained, pQCT yields excellent reproducibility at both the radius and
      tibia. These precision errors, in conjunction with changes in LSC for the pQCT
      measures, are useful for research and potential clinical applications.

PMID- 21723766
TI  - Closing the postfracture care gap using administrative health databases: design
      and implementation of a randomized controlled trial.
AB  - Postfracture care is suboptimal, and strategies to address this major care gap
      are urgently required. Case management is effective but is resource intensive and
      difficult to deliver to a widely scattered population. We describe the design and
      successful implementation of a randomized controlled trial (NCT00594789), which
      uses provincial administrative health databases to notify eligible physicians and
      patients after a major osteoporotic fracture that such fractures warrant
      additional assessment or pharmacologic treatment to prevent subsequent fractures.
      Men and women aged 50 yr or older residing in the Province of Manitoba, Canada,
      with a recently reported clinical fracture (hip, spine, humerus, and forearm)
      from medical claims data, and without recent bone mineral density (BMD) testing
      (in the last 3 yr) or osteoporosis therapy (in the last year), were randomized to
      3 groups: group 1 received usual care, group 2 (physicians only) had mailed
      notification to the primary care physicians (alert letter, BMD requisition, and
      management flowchart), and group 3 (physicians and patient) had both physician
      notifications and patient notification (alert letter). During the initial 10 mo
      (from June 2008 to March 2009), 2901 fracture patients meeting the inclusion
      criteria were randomized. Groups were well balanced. Direct costs related to the
      initiative (programming, case identification, and mailings) were Canadian dollars
      (CAD$)12,379 during the pilot phase, which translates to CAD$6.50 per
      notification (groups 2 and 3). Ongoing costs (which exclude the initial
      programming costs) are estimated at CAD$1.25 per notification. This postfracture
      intervention, based on medical claims data, provides an easy way to enhance
      postfracture care. The approach is scalable, can be delivered to a widely
      scattered population, and requires minimal infrastructure. This low-cost
      intervention may complement more resource-intensive programs based on case
      managers.

PMID- 21723767
TI  - Bone mineral density discordance and exploration of one of its causes.
AB  - Discordances between hip and spine areal density T-score values are common and
      incompletely understood. In a cohort of 1157 postmenopausal women, discordances
      of greater than 10% occurred in 91%, with spine bone mineral density (BMD) T
      scores significantly less negative than femoral neck (FN) T-scores (p<0.001).
      However, when T-scores based on bone mineral content (BMC) rather than BMD were
      used, the mean discordance was not significantly different from 0. This was
      largely because BMC at the FN had seemingly declined with age less rapidly than
      had BMD at that site. This can be explained by age-related areal expansion at the
      hip, which would be missed in the reported BMD output. One consequence is that if
      BMC-based T-scores are used to classify patients, substantially fewer individuals
      would have been judged osteoporotic in this cohort (two-thirds fewer for spine
      and three-fourths fewer for hip).

PMID- 21723768
TI  - Spine-hip T-score difference predicts major osteoporotic fracture risk
      independent of FRAX((r)): a population-based report from CAMOS.
AB  - The WHO fracture risk assessment tool (FRAX((r))) estimates an individual's 10-yr
      major osteoporotic and hip fracture probabilities. When bone mineral density
      (BMD) is included in the FRAX calculation, only the femoral neck measurement can
      be used. Recently, a procedure was reported for adjusting major osteoporotic
      fracture probability from FRAX with femoral neck BMD based on the difference
      (offset) between the lumbar spine and the femoral neck T-score values. The
      objective of the current analysis was to independently evaluate this algorithm in
      a population-based cohort of 4575 women and 1813 men aged 50 yr and older from
      the Canadian Multicentre Osteoporosis Study. For women and men combined, there
      was a 15% (95% confidence interval 7-24%) increase in major osteoporotic fracture
      risk for each offset T-score after adjusting for FRAX probability calculated with
      femoral neck BMD. The effect was stronger in women than men, but a significant
      sex interaction was not detected. Among the full cohort, 5.5% had their risk
      category reclassified after using the offset adjustment. Sex- and age-dependent
      offsets (equivalent to an offset based on Z-scores) showed improved risk
      classification among individuals designated to be at moderate risk with the
      conventional FRAX probability measurement. In summary, the T-score difference
      between the lumbar spine and femoral neck is an independent risk factor for major
      osteoporotic fractures that is independent of the FRAX probability calculated
      with femoral neck BMD.

PMID- 21723769
TI  - Effects of FRAX((r)) model calibration on intervention rates: a simulation study.
AB  - The WHO fracture risk assessment tool (FRAX((r))) estimates an individual's 10-yr
      major osteoporotic and hip fracture probabilities using a tool customized to the
      fracture epidemiology of a specific population. Incorrect model calibration could
      therefore affect performance of the model in clinical practice. The current
      analysis was undertaken to explore how simulated miscalibration in the FRAX((r))
      tool would affect the numbers of individuals meeting specific intervention
      criteria (10-yr major osteoporotic fracture probability >=20%, 10-yr hip fracture
      probability >=3%). The study cohort included 36,730 women and 2873 men aged 50yr
      and older with FRAX((r)) probability estimates using femoral neck bone mineral
      density. We simulated relative miscalibration error in 10% increments from -50%
      to +50% relative to a correctly calibrated FRAX((r)) model. We found that small
      changes in model calibration (even on the order of 10%) had large effects on the
      number of individuals qualifying for treatment. There was a steep gradient in the
      relationship between relative change in calibration and relative change in
      intervention rates: for every 1% change in calibration, there was a 2.5% change
      in intervention rates for women and 4.1% for men. For hip fracture probability,
      the gradient of the relationship was closer to unity. These results highlight the
      importance of FRAX((r)) model calibration, and speak to the importance of using
      high-quality fracture epidemiology in constructing FRAX((r)) tools.

PMID- 21723770
TI  - [Thyroid cancer following exposure to ionising radiation].
AB  - Exposure to ionising radiations during childhood increases the risk of thyroid
      cancer. Similar risk factors have been found after external radiation exposure or
      internal contamination with radioactive iodine isotopes. In case of contamination
      with radioiodines, administration of potassium iodide can prevent thyroid
      irradiation.

PMID- 21723771
TI  - Hallux metastasis revealing occult pulmonary squamous cell carcinoma.

PMID- 21723772
TI  - Prognostic interest of bone turnover markers in the management of postmenopausal
      osteoporosis.
AB  - OBJECTIVE: The aim was to review the literature dealing with the use of
      biochemical bone turnover markers (BTM) as predictors of bone loss and individual
      risk of fracture in postmenopausal osteoporosis. METHODS: We performed a
      generalized search in MEDLINE using Mesh Database from 1995 through 2009 with the
      following terms "biological markers" with "osteoporosis" or "bone resorption", or
      "bone fracture", "fracture risk". From this research, 197 abstracts were read, 91
      articles were screened then 43 original articles were selected. RESULTS: In most
      of the selected articles, the upper limit of the premenopausal range was used as
      a cut-off definition for increased bone resorption. Based on this review, we
      found a moderate and positive relationship between baseline level of BTM and rate
      of bone loss, more particularly for high level of BTM over 2 SD, especially when
      high turnover is constant in repeated sampling. In addition, an increase in BTM
      levels is associated with an increase in the risk of hip and non-vertebral
      fractures in elderly women over 75 years old. This is especially demonstrated
      with bone resorption markers (e.g. uCTX) in the highest quartile with an 1.7 to
      2.2 fold increase. The combination of data from bone mineral density (BMD) and
      bone resorption markers may improve fracture prediction. CONCLUSION: The
      measurement of BTM, together with the assessment of other risk factors including
      low BMD, will improve the prediction of risk fracture, but there is a lack of
      practical guidelines.

PMID- 21723773
TI  - Large-scale integrated super-computing platform for next generation virtual drug
      discovery.
AB  - Traditional drug discovery starts by experimentally screening chemical libraries
      to find hit compounds that bind to protein targets, modulating their activity.
      Subsequent rounds of iterative chemical derivitization and rescreening are
      conducted to enhance the potency, selectivity, and pharmacological properties of
      hit compounds. Although computational docking of ligands to targets has been used
      to augment the empirical discovery process, its historical effectiveness has been
      limited because of the poor correlation of ligand dock scores and experimentally
      determined binding constants. Recent progress in super-computing, coupled to
      theoretical insights, allows the calculation of the Gibbs free energy, and
      therefore accurate binding constants, for usually large ligand-receptor systems.
      This advance extends the potential of virtual drug discovery. A specific
      embodiment of the technology, integrating de novo, abstract fragment based drug
      design, sophisticated molecular simulation, and the ability to calculate
      thermodynamic binding constants with unprecedented accuracy, are discussed.

PMID- 21723774
TI  - Anti-infectives: can cellular screening deliver?
AB  - In an era of emerging and reemerging infectious diseases, and increasing
      multidrug resistance, the need to identify novel therapy is imperative.
      Unfortunately, the recent shift of the drug discovery paradigm from cellular
      screening to target-based approaches has not delivered the anticipated benefits.
      A recent renaissance of the traditional cell-based approach, on the other hand,
      has yielded several clinical candidates. Three successful examples are
      illustrated in this review, namely spiroindolone, thiazolidinone, and
      diarylquinoline for the treatment of malaria, hepatitis C virus, and
      tuberculosis, respectively. We describe in detail their identification, mechanism
      of action (MoA), and common features in the chemical structures. The challenges
      of the cell-based approach for anti-infective drug discovery are also discussed.
      We propose a shift from standard libraries to synthetic natural-product-like
      compound collections to improve the success of phenotypic lead finding and to
      facilitate the validation of hits.

PMID- 21723775
TI  - Chronic exposure to cigarette smoke increases matrix metalloproteinases and
      Filaggrin mRNA expression in oral keratinocytes: role of nicotine stimulation.
AB  - The vegetal alkaloid nicotine has been proved to modify the expression of many
      keratinocyte markers. In this study, the basal expression of MMP-2, MMP-9, MMP
      28, and Filaggrin has been evaluated in oral keratinocytes, in order to collect
      information about the ability of cigarette smoke to modify the basal expression
      pattern of these key enzymes in the absence of evident clinical signs in the oral
      epithelium. MMP-2, MMP-9, MMP-28, and Filaggrin basal expression was investigated
      by RT-PCR in oral keratinocytes derived from smokers (n=11), non-smokers (n=11),
      and ex-smokers (n=6) healthy volunteers. Moreover keratinocytes from non-smokers
      volunteers were stimulated in vitro by a single dose administration of nicotine
      (10 MUM) in order to estimate the effect of nicotinic receptors activation on the
      basal expression of the studied markers. RT-PCR analysis showed that all the
      markers studied were overexpressed in keratinocytes from smoker donors compared
      to control keratinocytes, while a single dose of nicotine was able to induce only
      Filaggrin expression in keratinocytes from non-smoking donors. Markers expression
      in ex-smoker donors was similar to that observed in normal non-smoker donors.
      These data indicate for the first time that cigarette smoking affects basal
      expression of some important markers in oral mucosa keratinocytes in vivo in the
      absence of clinical signs and that smoke quitting restores basal expression
      levels of these markers.

PMID- 21723776
TI  - Recent advances in mucin immunohistochemistry in salivary gland tumors and head
      and neck squamous cell carcinoma.
AB  - This review focuses on the immunohistochemical expression of members of the MUC
      type mucin family in salivary gland tumors and head and neck squamous cell
      carcinomas (HNSCC). Information is available on changes in the expression levels
      and distribution profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7
      in tumors of the salivary glands; and of MUC1, MUC2 and MUC4 in HNSCC. In
      salivary gland tumors the expression patterns of MUC2, MUC3, MUC5AC and MUC6
      appear to be very closely correlated with the histopathological tumor type
      indicating their potential use to improve diagnostic accuracy in salivary gland
      neoplasia. Some MUC-type mucins have emerged as valuable prognostic indicators in
      pleomorphic adenoma, mucoepidermoid carcinoma and HNSCC. Nine antibodies directed
      against different MUC1 antigens have thus far been examined in HNSCC of which
      monoclonal antibodies DF3, HMFG-1 and Ma695 have shown significant correlations
      with disease outcome. The importance of taking the specific anti-MUC antibody
      into consideration when comparing the results of different studies on MUC
      expression in salivary gland tumors and HNSCC is also highlighted in this review.

PMID- 21723777
TI  - Synthesis, DNA binding and cleavage activities of copper (II) thiocyanate complex
      with 4-(N,N-dimethylamino)pyridine and N,N-dimethylformamide.
AB  - Two novel copper(II) thiocyanate complexes with 4-(N,N-dimethylamino) pyridine
      and N,N-dimethylformamide (1) and with 4-(N,N-dimethylamino) pyridine (2) have
      been synthesized and characterized. The crystal and molecular structures of
      complexes 1 and 2 were determined by single-crystal X-ray diffraction.
      Antioxidative activity tests in vitro showed that complex 1 has significant
      antioxidative activity against hydroxyl free radicals from the Fenton reaction
      and also oxygen free radicals, which is better than standard antioxidants like
      vitamin C and mannitol. The interaction of complex 1 with calf thymus DNA was
      investigated by spectroscopic, cyclic voltammetry, and viscosity measurements.
      Results suggest that complex 1 can bind to DNA via partial intercalation mode.
      Moreover, complex 1 has been found to cleavage of plasmid DNA pBR322.

PMID- 21723778
TI  - Rhodamine-based derivatives for Cu2+ sensing: spectroscopic studies, structure
      recognition relationships and its test strips.
AB  - A rhodamine spirolactam/2-hydrazinopyridine derivative was synthesized and
      characterized, which exhibited high selectivity to Cu(2+) over other metal
      cations. The Cu(2+) recognition of this rhodamine derivative could be detected by
      fluorescence spectra, absorption spectra and an obvious color change which was
      observed easily by naked-eyes. The binding of this rhodamine derivative to Cu(2+)
      is instantaneous and sensitive. Moreover, a linear relationship was found between
      the fluorescence intensity at 575 nm from 0.5*10(-6) M to 3.0*10(-6) M of Cu(2+)
      concentration, and the limit of detection (LOD) was at low concentration of
      2.11*10(-8) M, this would benefit for the establishment of standard working
      curves in practical Cu(2+) detection. Additionally, we synthesized rhodamine
      spirolactam/2-aminomethylpyridine derivative and rhodamine
      spirolactam/phenylhydrazine derivative as analogs for elucidate the structure
      recognition relationships. Finally, we prepared the test strips of rhodamine
      spirolactam/2-hydrazinopyridine derivative for practical chromogenic the Cu(2+)
      detection.

PMID- 21723779
TI  - Safety of nerve conduction studies in patients with implantable cardioverter
      defibrillators.
AB  - OBJECTIVE: A patient with an implantable cardioverter-defibrillator (ICD) may
      suffer from neuromuscular disorders and may need to undergo a nerve conduction
      study (NCS). However, a NCS may be a source of electromagnetic interference
      (EMI). The aim of the present study was to investigate whether the interference
      from NCS used in a standardised test protocol affects ICD function. METHODS:
      Twenty patients (19 males; mean age of 59.8+/-9.9 years) with implantable ICDs
      (eight with integrated and 12 with true bipolar leads), treated with amiodarone
      and with symptoms suggesting neuropathy were included. NCS were conducted using
      repetitive stimulation with frequency of 2 Hz and single, rectangular pulses of
      intensity up to 100 mA. Stimulation was performed in standard sites including
      proximal sites in the arm. RESULTS: The impulses generated NCS were not detected
      by the ICD, irrespective of the site, rate or stimulus intensity. CONCLUSIONS:
      Standardised test protocol for an NCS is safe in patients with an ICD regardless
      of the leads type. SIGNIFICANCE: Current guidelines which limitate the NCS in
      patients with ICD may be the subject of revision.

PMID- 21723780
TI  - Surgery for mesothelioma? The debate continues.

PMID- 21723781
TI  - Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients
      with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and
      Radical Surgery (MARS) randomised feasibility study.
AB  - BACKGROUND: The effects of extra-pleural pneumonectomy (EPP) on survival and
      quality of life in patients with malignant pleural mesothelioma have, to our
      knowledge, not been assessed in a randomised trial. We aimed to assess the
      clinical outcomes of patients who were randomly assigned to EPP or no EPP in the
      context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS)
      feasibility study. METHODS: MARS was a multicentre randomised controlled trial in
      12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed
      mesothelioma and were deemed fit enough to undergo trimodal therapy were
      included. In a prerandomisation registration phase, all patients underwent
      induction platinum-based chemotherapy followed by clinical review. After further
      consent, patients were randomly assigned (1:1) to EPP followed by postoperative
      hemithorax irradiation or to no EPP. Randomisation was done centrally with
      computer-generated permuted blocks stratified by surgical centre. The main
      endpoints were feasibility of randomly assigning 50 patients in 1 year (results
      detailed in another report), proportion randomised who received treatment,
      proportion eligible (registered) who proceeded to randomisation, perioperative
      mortality, and quality of life. Patients and investigators were not masked to
      treatment allocation. This is the principal report of the MARS study; all
      patients have been recruited. Analyses were by intention to treat. This trial is
      registered, number ISRCTN95583524. FINDINGS: Between Oct 1, 2005, and Nov 3,
      2008, 112 patients were registered and 50 were subsequently randomly assigned: 24
      to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation
      were disease progression (33 patients), inoperability (five patients), and
      patient choice (19 patients). EPP was completed satisfactorily in 16 of 24
      patients assigned to EPP; in five patients EPP was not started and in three
      patients it was abandoned. Two patients in the EPP group died within 30 days and
      a further patient died without leaving hospital. One patient in the no EPP group
      died perioperatively after receiving EPP off trial in a non-MARS centre. The
      hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1.90
      (95% CI 0.92-3.93; exact p=0.082), and after adjustment for sex, histological
      subtype, stage, and age at randomisation the HR was 2.75 (1.21-6.26; p=0.016).
      Median survival was 14.4 months (5.3-18.7) for the EPP group and 19.5 months
      (13.4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned
      patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12
      patients in the EPP group and 19 in the no EPP group completed the quality of
      life questionnaires. Although median quality of life scores were lower in the EPP
      group than the no EPP group, no significant differences between groups were
      reported in the quality of life analyses. There were ten serious adverse events
      reported in the EPP group and two in the no EPP group. INTERPRETATION: In view of
      the high morbidity associated with EPP in this trial and in other non-randomised
      studies a larger study is not feasible. These data, although limited, suggest
      that radical surgery in the form of EPP within trimodal therapy offers no benefit
      and possibly harms patients. FUNDING: Cancer Research UK (CRUK/04/003), the June
      Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation
      Trust.

PMID- 21723782
TI  - TRPM8 and dyspnea: from the frigid and fascinating past to the cool future?
AB  - The transient receptor potential melastatin 8 (TRPM8) ion channel is gated by
      cool and noxious cold temperatures. The activation threshold is in the range of
      ~25-28 degrees C, which aligns well with the discharge of airway afferents. TRPM8
      is widely expressed across species and evolutionary changes in the TRPM8 amino
      acid sequence may tune the temperatures at which it is gated. The discovery of
      TRPM8 and its molecular/biophysical characterization provides a robust candidate
      for airway afferents responding to cool/cold temperatures. TRPM8 may provide a
      mechanistic link for the manipulation of respiratory sensations such as dyspnea
      or mechanisms leading to cold-induced asthma and cough.

PMID- 21723783
TI  - Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation.
AB  - It is controversial how cytotoxic T lymphocyte antigen (CTLA)-4, a co-inhibitory
      molecule, contributes to immunological tolerance and negative control of immune
      responses. Its role as an inducer of cell-intrinsic negative signals to activated
      effector T cells is well documented. However, there is accumulating evidence that
      CTLA-4 is essential for the function of naturally occurring Foxp3(+) regulatory T
      (Treg) cells, which constitutively express the molecule. CTLA-4 deficiency in
      Foxp3(+) Treg cells indeed impairs their in vivo and in vitro suppressive
      function. Further, Treg cells can modulate the function of CD80- and CD86
      expressing antigen-presenting cells via CTLA-4. Here we discuss how CTLA-4
      expression by one T cell can influence the activation of another in a cell non
      autonomous fashion and thus control immune responses.

PMID- 21723785
TI  - Testing platelet components for bacterial contamination.
AB  - Bacteria in transfused platelets can cause serious morbidity and, rarely, death.
      Most contaminating bacteria enter the blood at the time of venepuncture. While
      many of these contaminants fail to grow in the platelet unit, storage of
      platelets at 20-24 degrees C facilitates growth of some organisms, and the
      cumulative risk of severe sepsis increases with the storage age of platelet
      components. Several methods have been developed or adapted to attempt to detect
      contaminating bacteria with high sensitivity and specificity, but the perfect
      test has yet to be found. Testing early in the platelet component's shelf life,
      even using exquisitely sensitive culture-based tests, is compromised by major
      problems of sample error - there may be too few bacteria present at this stage to
      ensure that any practical sample volume contains even one of them. Culture
      techniques are too slow to be useful as a release test. On the other hand,
      available rapid tests are too insensitive to use early in the shelf life, and
      have yet to show convincingly that they are sensitive enough for testing close to
      the time of transfusion. Nevertheless testing for bacteria in platelet components
      represents a significant advance in blood transfusion safety, and prevents the
      transfusion of many hundreds of bacterially-contaminated platelet units each
      year.

PMID- 21723784
TI  - Exploring the link between glucocerebrosidase mutations and parkinsonism.
AB  - Clinical, genetic and pathological studies demonstrate that mutations in
      glucocerebrosidase (GBA), which encodes the lysosomal enzyme deficient in Gaucher
      disease (GD), are risk factors for Parkinson disease (PD) and related disorders.
      Some patients with GD and Gaucher carriers develop parkinsonism. Furthermore,
      subjects with PD have an increased frequency of GBA mutations. GBA-mutation
      carriers exhibit diverse parkinsonian phenotypes and have glucocerebrosidase
      positive Lewy bodies. Although the mechanism for this association is unknown, we
      present several theories, including protein aggregation, prion transmission,
      lipid accumulation and impaired autophagy, mitophagy or trafficking. Each model
      has inherent limitations, and a second-hit mutation might be essential.
      Elucidation of the basis for this link will have important consequences for
      studying these diseases and should provide insights into lysosomal pathways and
      potential treatment strategies.

PMID- 21723786
TI  - Timing clinical events in the treatment of pancreatitis and hypertriglyceridemia
      with therapeutic plasmapheresis.
AB  - BACKGROUND: Hyperlipidemic pancreatitis (HP) is caused by severe
      hypertriglyceridemia (SHTG). Evidence of SHTG refractoriness to standard medical
      treatment but not to therapeutic apheresis has increased in the last years.
      METHODS: Described is the timing of clinical events and the sequence of
      therapeutic plasma-exchange (TPE) procedures to treat pancreatitis due to SHTG in
      a male patient, Caucasian, aged 49years, referred to emergency for severe
      epigastric pain. There was no history of alcohol consumption, a pre-existing mild
      hyperlipidemia was treated with diet alone, and biliary imaging was normal.
      Physical examination revealed epigastric tenderness. Laboratory investigation
      revealed marked hypertriglyceridemia (11,355mg/dL; range: 30-150), and
      hypercholesterolemia (941mg/dL; range: 80-200). Serum amylase (Amy) and lipase
      (Lip) were increased: 160UI/L (range: 20-100) and 175UI/L (range: 13-60),
      respectively. A computerized tomography (CT) scan of the abdomen revealed a
      picture compatible with acute pancreatic phlogosis. It was diagnosed as "acute
      secondary pancreatitis (AP) and SHTG". RESULTS: The patient was successfully
      submitted to three sessions of TPE in emergency. He was released from hospital
      after 13 days of hospitalization. The levels of lipids and lipoproteins in his
      plasma were as follows: triglycerides (TG) 185mg/dL; total cholesterol (TC)
      179mg/dL; HDL-cholesterol (HDLC) 22mg/dL; LDL-cholesterol (LDLC) 120mg/dL.
      CONCLUSIONS: The decision to submit the patient with clinical evidence of HP
      caused by SHTG to apheresis was correct. The improvement in the clinical picture
      was fast and the recovery was complete.

PMID- 21723787
TI  - Emergency department care of seizure patients: demographic trends in southern
      Arizona.
AB  - The aim of this study was to describe the epidemiology of epilepsy and
      characteristics of patients with seizures who presented at the Yuma Regional
      Medical Center Emergency Department (YRMC ED) from 2005 to 2008. A seizure
      diagnosis was present in 2.7% of the patients, and accounted for 1.7% of all ED
      visits. Visits by patients identified as having epilepsy accounted for 0.3% of
      all ED visits. Patients with seizures were 2.8 times more likely to have used the
      ED for 2 or more years of the study period compared with control patients.
      Patients with at least one ED visit because of seizures were more likely to have
      multiyear visits, 43.6% visiting the ED within 2 or more years. Patients with
      epilepsy and seizures were significantly younger than the no-seizure control
      group. Patients who had ever been admitted to the ED for seizures or epilepsy had
      higher ED utilization even if the subsequent admissions were not seizure related.

PMID- 21723788
TI  - Posttraumatic epilepsy in Tunisia.
AB  - The medicolegal problems associated with posttraumatic epilepsy are frequently
      related to the assessment of the cause of traumatic brain injury and to the
      complexity of forensic examination. We carried out a study of 28 patients with
      posttraumatic epilepsy seen at the Neurological Department of Charles Nicolle
      Hospital in Tunis, Tunisia. We obtained a detailed history and performed
      neurological evaluation, EEG monitoring, and neuropsychological evaluation. For
      the forensic examination, we specified the date of stabilization and the damages
      to be compensated according to the different Tunisian forensic assessment scales.
      Traumatic brain injury was caused mainly by road traffic accidents. In 15
      patients, posttraumatic epilepsy was controlled by treatment after 5 years.
      Eighteen patients, victims of road traffic accidents, requested legal
      compensation. The date of stabilization was determined in 21 patients. Permanent
      partial disability was associated with severe trauma, young age, and uncontrolled
      seizures.

PMID- 21723789
TI  - Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress,
      and cognitive impairment in experimental models of epilepsy in rats.
AB  - The anticonvulsant effect of the hydroalcoholic extract of Zizyphus jujuba (HEZJ)
      fruit (100, 250, 500, and 1000 mg/kg, orally) was evaluated in experimental
      seizure models in rats. The effect of HEZJ on seizure-induced cognitive
      impairment, oxidative stress, and cholinesterase activity was also investigated.
      HEZJ (1000 mg/kg) exhibited maximum protection (100%) against generalized tonic
      clonic seizures in the pentylenetetrazole (PTZ) seizure model and and 66.7%
      protection against tonic hindlimb extension in the maximal electroshock (MES)
      seizure model. Significant impairment in cognitive functions was observed in both
      PTZ- and MES-challenged rats. Pretreatment with HEZJ resulted in significant
      improvement in learning and memory. HEZJ also reversed the oxidative stress
      induced by both PTZ and MES. The significant decrease in cholinesterase activity
      observed in the PTZ and MES models was significantly reversed by pretreatment
      with HEZJ. Thus, the present study demonstrates the anticonvulsant effect of HEZJ
      as well as amelioration of cognitive impairment induced by seizures in rats.

PMID- 21723790
TI  - Prognostic role of ERCC1 in advanced non-small-cell lung cancer: a systematic
      review and meta-analysis.
AB  - Small observational studies have demonstrated an association between high ERCC1
      expression level and poor prognosis in advanced NSCLC treated with platinum-based
      chemotherapy. This meta-analysis presents pooled estimates of association from 11
      studies. High ERCC1 patients had lower response rates and higher risk of death
      relative to low ERCC1 patients. These results support the prognostic significance
      of ERCC1 expression level in advanced NSCLC. BACKGROUND: Observational studies
      have demonstrated an association between excision repair cross-complementation
      group 1 (ERCC1) expression level and health outcomes in patients with advanced
      non-small-cell lung cancer (NSCLC) treated with platinum-based regimens. This
      analysis presents pooled estimates of association from these studies to better
      elucidate the prognostic role of ERCC1 in advanced NSCLC. METHODS: A systematic
      literature search was conducted using the MEDLINE, EMBASE, and American Society
      of Clinical Oncology (ASCO) annual meeting databases from June 1995 to December
      2010. Included studies were evaluated for clinical, methodological, and
      statistical heterogeneity. Pooled analyses were conducted using fixed and random
      effects models. RESULTS: In high ERCC1 expression versus low ERCC1 expression
      patients, pooled analysis results demonstrated a significantly lower response
      (risk ratio [RR], 0.80, 0.66-0.98) and significantly higher risk of death (hazard
      ratio [HR], 2.04, (1.48-2.80)), respectively. Subgroup analyses demonstrated
      significant heterogeneity in outcomes by ERCC1 measurement method (I(2): 90.7%, P
      = 0.001) and patient population ethnicity (I(2): 66%, P = 0.003). CONCLUSION:
      This study's findings support the hypothesis that ERCC1 expression is associated
      with response rate and overall survival (OS) in patients with advanced NSCLC
      treated with platinum-based chemotherapy. Heterogeneity in subgroup analyses
      demonstrates the need for standardized methods to classify ERCC1 expression
      level, studies evaluating the association between ERCC1 expression and OS in non
      Asian populations, and studies evaluating interaction between ERCC1 and other
      known prognostic factors in advanced NSCLC.

PMID- 21723791
TI  - Integration of EGFR inhibitors and conventional chemotherapy in the treatment of
      non-small-cell lung cancer.
AB  - INTRODUCTION/BACKGROUND: Given the limited gains of traditional chemotherapy in
      improving outcomes in patients with advanced non-small-cell lung cancer (NSCLC),
      recent research efforts have investigated the integration of targeted agents into
      the treatment algorithm. MATERIALS AND METHODS: Searches of PubMed and of recent
      results from key oncology congresses were performed to identify relevant articles
      and abstracts. Initial phase III trials combining the reversible epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib
      with platinum-based doublets as first-line therapy failed to demonstrate an
      overall survival advantage in unselected patients with NSCLC. However, in recent
      years, there has been substantial progress in understanding the determinants of
      response to EGFR TKI therapy, including the presence of activating EGFR
      mutations, which has been reflected in clinical trials specifically evaluating
      these patient populations. In addition, evidence suggesting potential mechanistic
      interference between concurrent EGFR TKIs and chemotherapy has also been
      observed, fueling interest in sequential or intermittent dosing. EGFR-targeted
      agents such as the multitargeted TKI vandetanib and the next-generation EGFR TKIs
      afatinib (BIBW 2992) and PF00299804 are also under clinical investigation for the
      treatment of NSCLC, both alone and in combination with chemotherapy. CONCLUSIONS:
      Trials evaluating various regimens of EGFR-targeted agents and chemotherapy are
      planned and/or underway and will hopefully define the role of integrated therapy
      in NSCLC.

PMID- 21723793
TI  - Review article: loss of the calcium-sensing receptor in colonic epithelium is a
      key event in the pathogenesis of colon cancer.
AB  - The calcium-sensing receptor (CaSR) is expressed abundantly in normal colonic
      epithelium and lost in colon cancer, but its exact role on a molecular level and
      within the carcinogenesis pathway is yet to be described. Epidemiologic studies
      show that inadequate dietary calcium predisposes to colon cancer; this may be due
      to the ability of calcium to bind and upregulate the CaSR. Loss of CaSR
      expression does not seem to be an early event in carcinogenesis; indeed it is
      associated with late stage, poorly differentiated, chemo-resistant tumors.
      Induction of CaSR expression in neoplastic colonocytes arrests tumor progression
      and deems tumors more sensitive to chemotherapy; hence CaSR may be an important
      target in colon cancer treatment. The CaSR has a complex role in colon cancer;
      however, more investigation is required on a molecular level to clarify its exact
      function in carcinogenesis. This review describes the mechanisms by which the
      CaSR is currently implicated in colon cancer and identifies areas where further
      study is needed.

PMID- 21723792
TI  - A randomized phase II study of paclitaxel and bevacizumab with and without
      gemcitabine as first-line treatment for metastatic breast cancer.
AB  - BACKGROUND: The addition of bevacizumab to paclitaxel improved progression-free
      survival (PFS) of patients with metastatic breast cancer (MBC). We examined the
      efficacy and safety of adding gemcitabine to paclitaxel/bevacizumab (PB).
      PATIENTS AND METHODS: In this multicenter, open-label, randomized phase II trial,
      women with locally advanced or MBC were randomly assigned to receive paclitaxel
      90 mg/m(2) (days 1, 8, 15) and bevacizumab 10 mg/kg (days 1, 15) with or without
      gemcitabine 1500 mg/m(2) (days 1, 15) in 28-day cycles. Patients with prior
      cytotoxic therapy for MBC were ineligible. The primary endpoint was investigator
      assessed overall response rate (ORR); secondary endpoints were PFS, overall
      survival (OS), safety, and quality of life. RESULTS: Ninety-four patients
      received PB, and 93 received paclitaxel/bevacizumab/gemcitabine (PB+G). The ORRs
      were 48.9% (95% confidence interval [CI], 38.5%-59.5%) and 58.7% (95% CI, 47.9%
      68.9%; P = .117) with PB and PB+G, respectively. The median PFS was 8.8 months
      (95% CI, 8.1-10.4 months) and 11.3 months (95% CI, 9.7-12.7 months; P = .247;
      hazard ratio, 0.82); the median OS was 25.0 months (95% CI, 18.8-not assessable
      [N/A] months) and 24.3 months (95% CI, 20.3-N/A months; P = .475; hazard ratio,
      0.84), with PB and PB+G, respectively. There was significantly more grade 3-4
      neutropenia (P = .001) and dyspnea (P = .014) with PB+G. Patients treated with PB
      experienced more improvement in total FACT-B (Functional Assessment of Cancer
      Therapy-Breast) (P = .021), FACT-B Social/Family Well-being (P = .041), and
      Breast Cancer-Additional Concerns (P = .008) scores than patients treated with
      PB+G. CONCLUSION: The addition of gemcitabine to PB was not associated with a
      statistically significant improvement in ORR. Treatment with PB+G increased the
      incidence of severe neutropenia and dyspnea, although the regimen generally was
      well tolerated.

PMID- 21723794
TI  - Prognostic factors for survival in patients with recurrence of muscle invasive
      bladder cancer after treatment with curative intent.
AB  - Prognostic factors for survival after recurrent MIBC are unknown and were
      evaluated using a population-based series of 1409 MIBC patients. 330 Patients who
      underwent RC or RT with curative intent and who suffered from recurrence were
      selected. Multivariable survival analyses were performed. Clinicopathological
      factors that predict survival after recurrence are recurrence location, treatment
      for recurrence and age at recurrence diagnosis. PURPOSE: We conducted this study
      to evaluate the prognostic factors for survival among patients with recurrent
      muscle-invasive bladder cancer (MIBC) after initial treatment with curative
      intent. PATIENTS AND METHODS: Clinical data were collected from a population
      based series of 1409 patients with MIBC. We selected 330 patients who underwent
      radical cystectomy (RC) or radiotherapy (RT) for urothelial carcinoma with
      curative intent and who experienced recurrence. Multivariate survival analyses
      were performed with death from MIBC as the endpoint. Covariates were gender, time
      to recurrence, age at diagnosis of recurrence, recurrence multiplicity,
      localization, and treatment for recurrence. Analyses were performed separately
      for patients initially treated with RC (i-RC) or external beam radiotherapy (i
      EBRT). RESULTS: Patients with recurrence after i-RC showed a 1- and 3-year
      survival of 17% and 6%, respectively. Localization and treatment for recurrence
      were significantly associated with survival. Patients with recurrence after i
      EBRT showed a 1- and 3-year survival of 31% and 12%, respectively. Age at
      diagnosis of recurrence, localization, and treatment for recurrence were
      significantly associated with survival. CONCLUSION: This study confirms the
      extremely poor prognosis after recurrence of MIBC in patients initially treated
      with surgery or RT. Clinicopathologic factors that predict survival after disease
      recurrence are location of recurrence, treatment for recurrence, and age at
      diagnosis of recurrence. Improved diagnosis of primary MIBC to detect
      extravesical disease and more effective therapeutic approaches to target
      recurrent MIBC are needed.

PMID- 21723795
TI  - Individual learning curve reduces the clinical value of urinary cytology.
AB  - The aim of the study was to define the learning curve of a single cytologist as a
      limitation of urinary cytology. A total of 1034 cytologic and histologic findings
      of patients undergoing transurethral resection of the bladder for suspicion of
      bladder cancer were reviewed, and cytologic evaluations of a single cytologist
      from the beginning of his learning period were compared with the results of a
      cytologist at a national reference center. Our results showed that the individual
      learning curve has a significant impact on the quality of urine cytology.
      BACKGROUND: To define the learning curve of a single cytologist as a limitation
      of urinary cytology and to compare his results with a reference center for
      urinary cytology. PATIENTS AND METHODS: Cytologic and histologic findings of
      patients undergoing transurethral resection of the bladder for suspicion of
      bladder cancer were reviewed. Cytologic evaluations from a single local
      cytologist during his learning period and of a cytologist of a national reference
      center were compared. Changes of sensitivity and specificity of cytology from the
      local cytologist over the time period were assessed. Differences were estimated
      by using kappa statistics. RESULTS: The local cytologist evaluated 1034 cytologic
      findings. Sensitivity and specificity of cytology estimated by the local
      cytologist were 86% and 66% at the beginning of the learning period, but 68% and
      84% at the end of it (P <= .05). In high-grade carcinomas, sensitivity did not
      decrease over the years (P > .05). In contrast, the sensitivity in the diagnosis
      of low-grade tumors decreased from 86% to 56% (P <= .05). The reference center
      estimated a constant sensitivity and specificity of 59% and 97%, respectively.
      Agreement of findings between local and national cytologists increased
      significantly over the learning period (P < .05). CONCLUSION: The individual
      learning curve has a significant impact on the quality of urinary cytology. Both
      specificity of cytology and sensitivity for low-grade tumors changed
      significantly when done by a local cytologist at the beginning of learning
      period. These findings emphasize the impact of the individual learning curve on
      the clinical value of urinary cytology in diagnosis of bladder cancer.

PMID- 21723796
TI  - Peritoneal relapse of testicular seminomatous germ cell tumor treated
      successfully with salvage chemotherapy and autologous stem cell transplantation.

PMID- 21723797
TI  - Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate
      dehydrogenase, and prostate-specific antigen for determining treatment response
      in patients with metastatic prostate cancer.
AB  - Our aim was to determine the utility of circulating micro RNA miR-141 as a
      potential biomarker of therapeutic response in prostate cancer (CaP) patients. We
      compared the values of miR-141 in plasma of 21 CaP patients to the levels of
      prostate specific antigen (PSA), circulating tumor cells (CTC) and lactate
      dehydrogenase (LDH). Data suggest a strong correlation of miR-141 values and
      clinical course. For prostate cancer (CaP), the measurement of prostate-specific
      antigen (PSA) and radiographic studies do not adequately predict response to
      therapy and survival, and, therefore, new relevant biomarkers are needed. We and
      other researchers have shown that longitudinal measurements of PSA, circulating
      tumor cells (CTC), and lactate dehydrogenase (LDH) may aid in predicting response
      to therapy. Results of recent studies have determined that circulating microRNA
      (miRNA) miR-141 is detected in plasma of patients with CaP. We, therefore,
      compared the temporal changes of miR-141 with the levels of CTC, LDH, and PSA in
      21 patients with CaP, and longitudinally examined these markers alone or in
      combinations to determine the utility of miR-141 in the predicting a patient's
      clinical course and response to therapy. Levels of miR-141 in plasma of 21
      patients with CaP were measured by using quantitative reverse transcription
      polymerase chain reaction. A total of 35 intervals were assessed. Directional
      changes (increasing or decreasing) in PSA, CTC, and miR-141 had sensitivity in
      predicting clinical outcome (progression vs. nonprogressing) of 78.9%. Logistic
      regression modeling of the probability of clinical progression demonstrates that
      miR-141 levels predicted clinical outcomes with an odds ratio of at least 8.3.
      miR-141 also had the highest correlation with temporal changes of PSA with a
      correlation of R = 0.77 (P < .001). In this retrospective study, miR-141
      demonstrated a similar ability to predict clinical progression when compared with
      other clinically validated biomarkers. Furthermore, miR-141 demonstrated high
      correlation with changes of the other biomarkers.

PMID- 21723798
TI  - [Idiopathic short stature. A literature review and update].
AB  - Idiopathic short stature (ISS) refers to all clinical conditions involving an
      alteration of growth (height<-2 SD) of unknown cause, with preservation of
      proportionality among body segments, with the expectation of adult height < -2
      SDS, and in which a diagnosis of constitutional delay of growth and development
      has been previously ruled out. ISS is an exclusion diagnostic which requires
      clinical, biochemical, hormonal and molecular studies in order to rule out all
      known causes of growth retardation and short stature. ISS is a frequent diagnosis
      among children with short stature. Despite its frequency, there is still
      controversy on the best diagnostic and therapeutic approach when treating
      patients with ISS. This consensus document contains updated information on the
      definition, diagnosis and treatment of ISS, and provides new data and
      recommendations that have not been addressed in previous documents.

PMID- 21723799
TI  - Eyebrow reconstruction in dormant keratosis pilaris atrophicans.
AB  - A novel and successful case of eyebrow reconstruction, in dormant keratosis
      pilaris atrophicans, is presented. Keratosis pilaris atrophicans is a benign
      hereditary disorder of unknown aetiology. Grouped keratotic follicular papules
      and perifollicular erythema affect the cheeks and eyebrows, with a subsequent
      atrophic stage that results in scarring and alopecia. It often presents during
      early infancy with remission during adulthood. A 33 year old man presented with
      scarring and alopecia of the eyebrows and was followed over a total 4 year period
      during which reconstruction was achieved using individual hair follicle
      micrografts. Composite scalp grafts and flaps, more often than hair follicle
      micrografting techniques, are described in the literature for reconstruction of
      the eyebrows in a range of conditions. This case provides an encouraging example
      of successful micrografting in dormant inflammatory cutaneous disease.

PMID- 21723801
TI  - Allele frequencies of the five new generation forensic STR (D1S1656, D2S441,
      D10S1248, D12S391 and D22S1045) in the population from Rio Grande do Sul,
      Southern Brazil.

PMID- 21723800
TI  - The development and validation of a single SNaPshot multiplex for tiger species
      and subspecies identification--implications for forensic purposes.
AB  - The tiger (Panthera tigris) is currently listed on Appendix I of the Convention
      on the International Trade in Endangered Species of Wild Fauna and Flora; this
      affords it the highest level of international protection. To aid in the
      investigation of alleged illegal trade in tiger body parts and derivatives,
      molecular approaches have been developed to identify biological material as being
      of tiger in origin. Some countries also require knowledge of the exact tiger
      subspecies present in order to prosecute anyone alleged to be trading in tiger
      products. In this study we aimed to develop and validate a reliable single assay
      to identify tiger species and subspecies simultaneously; this test is based on
      identification of single nucleotide polymorphisms (SNPs) within the tiger
      mitochondrial genome. The mitochondrial DNA sequence from four of the five extant
      putative tiger subspecies that currently exist in the wild were obtained and
      combined with DNA sequence data from 492 tiger and 349 other mammalian species
      available on GenBank. From the sequence data a total of 11 SNP loci were
      identified as suitable for further analyses. Five SNPs were species-specific for
      tiger and six amplify one of the tiger subspecies-specific SNPs, three of which
      were specific to P. t. sumatrae and the other three were specific to P. t.
      tigris. The multiplex assay was able to reliably identify 15 voucher tiger
      samples. The sensitivity of the test was 15,000 mitochondrial DNA copies
      (approximately 0.26 pg), indicating that it will work on trace amounts of tissue,
      bone or hair samples. This simple test will add to the DNA-based methods
      currently being used to identify the presence of tiger within mixed samples.

PMID- 21723802
TI  - The EUROP total knee prosthesis: a ten-year follow-up study of a posterior
      cruciate-retaining design.
AB  - INTRODUCTION: The success of total knee arthroplasty is measured by pain relief,
      functional recovery, and implant survival duration. The aim of the present study
      was to evaluate the long-term clinical, functional and radiological results of
      the posterior cruciate ligament (PCL)-retaining fixed bearing EUROP implant.
      HYPOTHESIS: The long-term results of EUROP implants are similar to those reported
      with comparable prostheses. PATIENTS AND METHODS: We performed a prospective,
      monocentric study of a series of 121 cemented EUROP total knee arthroplasties,
      implanted between 1994 and 1996 in 117 patients mean age 73. A clinical and
      radiological evaluation was performed at 10 years of follow-up according to the
      International Knee Society (IKS) score. Twenty-three patients died, 14 were lost
      to follow-up, 43 underwent clinical and radiological evaluation and 37 were
      questioned by telephone. RESULTS: The preoperative IKS knee score was 31 points
      (0-60) and increased to 88 points (30-98) at final follow-up, IKS function
      increased from 40 (0-90) to 80 points (25-100). Radiolucencies were observed in
      56% of the condyles and 60% of tibial plates. Ninety-three percent of these
      radiolucent lines were less than 1mm wide. Three patients underwent revision TKA
      at 32 months, eight and 11 years respectively. Global implant survival was 99% at
      five years, 97.8% at 10 years and 95.8% at 12 years. DISCUSSION: The clinical and
      radiological results of the cruciate-retaining fixed bearing EUROP total knee
      arthroplasties, with three cases of revision arthroplasty at 12 years of follow
      up are satisfactory and comparable to similar implants.

PMID- 21723803
TI  - Pitfalls in familial mediterranean fever: acute intestinal
      strangulation/obstruction due to primary adhesions.
AB  - Familial Mediterranean Fever (FMF) presents in 90% of patients with painful
      attacks of peritoneal inflammation, which may mimic an acute surgical abdomen.
      These episodes characteristically resolve spontaneously within 72 hours. However,
      recurrent episodes of primary peritonitis may lead to the development of primary
      intraperitoneal adhesions, even in the absence of previous abdominal surgery.
      When an atypical bout of pain fails to resolve spontaneously and rapidly, the
      surgeon must consider the diagnosis of intestinal obstruction due to an adhesive
      band with the associated risk of strangulation with bowel necrosis. In this case
      report, we describe this rare but classical presentation of FMF for which any
      delay in diagnosis or treatment may result in severe morbidity.

PMID- 21723804
TI  - Effect of occlusal contact stability on the jaw closing point during tapping
      movements.
AB  - PURPOSE: We studied the relationship between tapping point reproducibility and
      stability of occlusal contacts at maximum intercuspation. METHODS: Tapping
      movements of 12 adult volunteers who had dentition with natural teeth were
      recorded, and distances between the tapping point (TP) and the intercuspal
      position (ICP) at the incisal point were calculated. Occlusal contacts at the ICP
      of individual subjects were also evaluated with black-colored silicone impression
      material. The correlation between TP-ICP distance and occlusal contact stability
      was studied. RESULTS: TP-ICP distance exhibited negative correlations with the
      total number of teeth showing occlusal contact at the ICP. Standard deviations of
      TP-ICP distance also negatively correlated with the extension of occlusal contact
      area over dentition. CONCLUSIONS: This finding indicates that occlusal contacts
      at the ICP affect the kinematic behavior of tapping movements. The results of
      this study also suggest that jaw movement data may provide useful clinical
      information for the evaluation of occlusal contact at ICP.

PMID- 21723805
TI  - Translating trial-based molecular monitoring into clinical practice: importance
      of international standards and practical considerations for community
      practitioners.
AB  - The success of tyrosine kinase inhibition of the BCR-ABL fusion gene with
      imatinib in the treatment of chronic myeloid leukemia (CML) has resulted in the
      use of molecular detection techniques for routine clinical management. Current
      clinical guidelines recommend the use of molecular testing of BCR-ABL transcript
      levels by quantitative real-time transcriptase polymerase chain reaction (qRT
      PCR) every 3 to 6 months. However, qRT-PCR methods have not yet been
      standardized, particularly in the United States, where most patients are
      initially treated outside of academic practices. The lack of standard methods for
      molecular monitoring has resulted in the failure to follow National Comprehensive
      Cancer Network and European LeukemiaNet guideline recommendations and in the
      misinterpretation of test results. Standardization of molecular monitoring
      methods and adherence to guideline recommendations are important for optimal
      patient management. In this article, we provide an update on the current clinical
      trial results by using the molecular technique to monitor patient response.
      Current problems and efforts in standardizing the qRT-PCR technique and reporting
      are reviewed. We provide examples of potential problems of various reference
      laboratory reports and present recommendations for assessing molecular test
      results. These recommendations seem particularly important because nilotinib and
      dasatinib appear to have improved the molecular response in the initial treatment
      of CML.

PMID- 21723806
TI  - MR evaluation of biliary-enteric anastomotic stricture: does contrast-enhanced
      T1W MRC provide additional information?
AB  - BACKGROUND AND OBJECTIVE: To compare T2W-MRCP and T1W contrast-enhanced MRC (CE
      MRC) using Gd-BOPTA for evaluation of biliary-enteric anastomotic (BEA)
      stricture. PATIENTS AND METHODS: Twenty-one patients who were suspected to have
      BEA stricture underwent T2W-MRCP and CE-MRC on a 1.5T scanner. Images were
      evaluated for evidence of anastomotic stricture. Composite gold standard was used
      including the findings on percutaneous transhepatic cholangiogram or percutaneous
      transhepatic biliary dilatation, surgery, alkaline phosphatase level and clinical
      follow-up. RESULTS: The sensitivity, specificity, positive predictive value (PPV)
      and negative predictive value (NPV) of T2W-MRCP for the diagnosis of anastomotic
      stricture were 94.4%, 80%, 94.4% and 80% respectively. On CE-MRC, biliary
      excretion was seen in only 60.87% anastomoses and only these were taken for
      analysis. The sensitivity, specificity, PPV and NPV of CE-MRC for the diagnosis
      of anastomotic stricture were 40%, 75%, 80% and 33.3%. The combined evaluation of
      T2W-MRCP and CE-MRC showed sensitivity, specificity, PPV and NPV of 83.3%, 80%,
      93.8% and 57.1%. CONCLUSION: At present, T2W-MRCP is still the diagnostic
      modality of choice in the evaluation of patients with BEA stricture and the usage
      of Gd-BOPTA enhanced MRC is inappropriate in this setting.

PMID- 21723807
TI  - Impact of histidine residue on chelating ability of 2'-deoxyriboadenosine.
AB  - Copper(II) complexes with a new chelator-type nucleoside-histidine modified 2'
      deoxyriboadenosine (N-[(9-beta-D-2'-deoxyribofuranosylpurin-6-yl)
      carbamoyl]histidine) were studied by potentiometric and spectroscopic (UV
      visible, CD, EPR) techniques, in conjunction with computer modeling optimization.
      The ligand can act as bidentate or tridentate depending on pH range. In acidic pH
      a very stable dimeric complex Cu(2)L(2) predominates with coordination spheres of
      both metal ions composed of oxygen atoms from carboxylic groups, one oxygen atom
      from ureido group and two nitrogen atoms derived from purine base and histidine
      ring. Above pH 5, deprotonation of carbamoyl nitrogens leads to the formation of
      CuL(2), Cu(2)L(2)H(-1) and Cu(2)L(2)H(-2) species. The CuL(2)H(-1) and CuL(2)H(
      2) complexes with three or four nitrogens in Cu(II) coordination sphere have been
      detected in alkaline medium. Our findings suggest that N-[(9-beta-D-2'
      deoxyribofuranosylpurin-6-yl)-carbamoyl]histidine chelates copper(II) ions very
      efficiently. The resulting complex might be used as an alternative base-pairing
      mode in which hydrogen-bonded base pairs present in natural DNA are replaced by
      metal-mediated ones.

PMID- 21723808
TI  - Electron paramagnetic resonance spectroscopy measures the distance between the
      external beta-strands of folded alpha-synuclein in amyloid fibrils.
AB  - The misfolding of alpha-synuclein (alphaS) to a cross-beta-sheet amyloid
      structure is associated with pathological conditions in Parkinson's and other
      neurodegenerative diseases. Using pulse electron paramagnetic resonance
      spectroscopy combined with a cross-labeling strategy involving four double
      mutants, we were able to determine the intramolecular distance between the
      extremal beta-strands. The distance of 4.5 +/- 0.5 nm is in good agreement with
      the dimensions of a protofilament reported by other low-resolution techniques,
      such as x-ray scattering and atomic force microscopy.

PMID- 21723809
TI  - Lever-arm mechanics of processive myosins.

PMID- 21723810
TI  - Multicellular model for intercellular synchronization in circadian neural
      networks.
AB  - We developed a multicellular model characterized by a high degree of
      heterogeneity to investigate possible mechanisms that underlie circadian network
      synchronization and rhythmicity in the suprachiasmatic nucleus (SCN). We
      populated a two-dimensional grid with 400 model neurons coupled via gamma
      aminobutyric acid (GABA) and vasoactive intestinal polypeptide (VIP)
      neurotransmitters through a putative Ca(2+) mediated signaling cascade to
      investigate their roles in gene expression and electrical firing activity of cell
      populations. As observed experimentally, our model predicted that GABA would
      affect the amplitude of circadian oscillations but not synchrony among individual
      oscillators. Our model recapitulated experimental findings of decreased synchrony
      and average periods, loss of rhythmicity, and reduced circadian amplitudes as VIP
      signaling was eliminated. In addition, simulated increases of VIP reduced
      periodicity and synchrony. We therefore postulated a physiological range of VIP
      within which the system is able to produce sustained and synchronized
      oscillations. Our model recapitulated experimental findings of diminished
      amplitudes and periodicity with decreasing intracellular Ca(2+) concentrations,
      suggesting that such behavior could be due to simultaneous decrease of individual
      oscillation amplitudes and population synchrony. Simulated increases in Cl(-)
      levels resulted in increased Cl(-) influx into the cytosol, a decrease of
      inhibitory postsynaptic currents, and ultimately a shift of GABA-elicited
      responses from inhibitory to excitatory. The simultaneous reduction of IPSCs and
      increase in membrane resting potential produced GABA dose-dependent increases in
      firing rates across the population, as has been observed experimentally. By
      integrating circadian gene regulation and electrophysiology with intracellular
      and intercellular signaling, we were able to develop the first (to our knowledge)
      multicellular model that allows the effects of clock genes, electrical firing,
      Ca(2+), GABA, and VIP on circadian system behavior to be predicted.

PMID- 21723811
TI  - Trafficking motifs as the basis for two-compartment signaling systems to form
      multiple stable states.
AB  - Transport of molecules in cells is a central part of cell biology. Frequently
      such trafficking is not just for material transport, but also for information
      propagation, and serves to couple signaling circuits across cellular
      compartments. Here, I show that trafficking transforms simple local signaling
      pathways into self-organizing systems that span compartments and confer distinct
      states and identities to these compartments. I find that three motifs encapsulate
      the responses of most single-compartment signaling pathways in the context of
      trafficking. These motifs combine with different trafficking reactions to
      generate a diverse set of cellular functions. For example, trafficked bistable
      switches can oscillate or become quad- or tristable, depending on trafficking
      mechanisms and rates. Furthermore, the analysis shows how compartments
      participating in traffic can settle to distinct molecular compositions
      characteristic of distinct organelle identities. This general framework shows how
      the interplay between molecular movement and local reactions can generate many
      system functions, and give distinct identities to different parts of the cell.

PMID- 21723812
TI  - Quantification of collagen organization in the peripheral human cornea at micron
      scale resolution.
AB  - The collagen microstructure of the peripheral cornea is important in stabilizing
      corneal curvature and refractive status. However, the manner in which the
      predominantly orthogonal collagen fibrils of the central cornea integrate with
      the circumferential limbal collagen is unknown. We used microfocus wide-angle x
      ray scattering to quantify the relative proportion and orientation of collagen
      fibrils over the human corneolimbal interface at intervals of 50 MUm. Orthogonal
      fibrils changed direction 1-1.5 mm before the limbus to integrate with the
      circumferential limbal fibrils. Outside the central 6 mm, additional
      preferentially aligned collagen was found to reinforce the cornea and limbus. The
      manner of integration and degree of reinforcement varied significantly depending
      on the direction along which the limbus was approached. We also employed small
      angle x-ray scattering to measure the average collagen fibril diameter from
      central cornea to limbus at 0.5 mm intervals. Fibril diameter was constant across
      the central 6 mm. More peripherally, fibril diameter increased, indicative of a
      merging of corneal and scleral collagen. The point of increase varied with
      direction, consistent with a scheme in which the oblique corneal periphery is
      reinforced by chords of scleral collagen. The results have implications for the
      cornea's biomechanical response to ocular surgeries involving peripheral
      incision.

PMID- 21723813
TI  - Cell cytoskeleton and tether extraction.
AB  - We perform a detailed investigation of the force * deformation curve in tether
      extraction from 3T3 cells by optical tweezers. Contrary to conventional wisdom
      about tethers extracted from cells, we find that actin filaments are present
      within them, so that a revised theory of tether pulling from cells is called for.
      We also measure steady and maximum tether force values significantly higher than
      previously published ones for 3T3 cells. Possible explanations for these
      differences are investigated. Further experimental support of the theory of force
      barriers for membrane tube extension is obtained. The potential of studies on
      tether pulling force * deformation for retrieving information on membrane
      cytoskeleton interaction is emphasized.

PMID- 21723814
TI  - A novel method for measuring tension generated in stress fibers by applying
      external forces.
AB  - The distribution of contractile forces generated in cytoskeletal stress fibers
      (SFs) contributes to cellular dynamic functions such as migration and
      mechanotransduction. Here we describe a novel (to our knowledge) method for
      measuring local tensions in SFs based on the following procedure: 1), known
      forces of different magnitudes are applied to an SF in the direction
      perpendicular to its longitudinal axis; 2), force balance equations are used to
      calculate the resulting tensions in the SF from changes in the SF angle; and 3),
      the relationship between tension and applied force thus established is
      extrapolated to an applied force of zero to determine the preexisting tension in
      the SF. In this study, we measured tensions in SFs by attaching magnetic
      particles to them and applying known forces with an electromagnetic needle.
      Fluorescence microscopy was used to capture images of SFs fluorescently labeled
      with myosin II antibodies, and analysis of these images allowed the tension in
      the SFs to be measured. The average tension measured in this study was comparable
      to previous reports, which indicates that this method may become a powerful tool
      for elucidating the mechanisms by which cytoskeletal tensions affect cellular
      functions.

PMID- 21723815
TI  - Glu-286 rotation and water wire reorientation are unlikely the gating elements
      for proton pumping in cytochrome C oxidase.
AB  - One of the key unresolved issues regarding proton pumping in cytochrome c oxidase
      (CcO) is the identity of the gating element that prevents the backflow of
      protons. In this study, we analyze two popular proposals for this element:
      isomerization of the key branching residue (Glu-286) and (re)orientation of water
      molecules in the hydrophobic cavity. Using a multifaceted set of computational
      analyses that involve CcO embedded in either an implicit or explicit treatment of
      lipid membrane, we show that neither Glu-286 nor active-site water likely
      constitutes the gating element. Detailed energetic and structural analyses of the
      simulation results indicate that the gating-relevant properties of these
      structural motifs observed in previous work are likely a result of the simplified
      computational models employed in those studies.

PMID- 21723816
TI  - Origins and consequences of velocity fluctuations during DNA passage through a
      nanopore.
AB  - We describe experiments and modeling results that reveal and explain the
      distribution of times that identical double-stranded DNA (dsDNA) molecules take
      to pass through a voltage-biased solid-state nanopore. We show that the observed
      spread in this distribution is caused by viscous-drag-induced velocity
      fluctuations that are correlated with the initial conformation of nanopore
      captured molecules. This contribution exceeds that due to diffusional Brownian
      motion during the passage. Nevertheless, and somewhat counterintuitively, the
      diffusional Brownian motion determines the fundamental limitations of rapid DNA
      strand sequencing with a nanopore. We model both diffusional and conformational
      fluctuations in a Langevin description. It accounts well for passage time
      variations for DNA molecules of different lengths, and predicts conditions
      required for low-error-rate nanopore-strand DNA sequencing with nanopores.

PMID- 21723817
TI  - Cytoplasmic domain filter function in the mechanosensitive channel of small
      conductance.
AB  - Mechanosensitive channels, inner membrane proteins of bacteria, open and close in
      response to mechanical stimuli such as changes in membrane tension during osmotic
      stress. In bacteria, these channels act as safety valves preventing cell lysis
      upon hypoosmotic cell swelling: the channels open under membrane tension to
      release osmolytes along with water. The mechanosensitive channel of small
      conductance, MscS, consists, in addition to the transmembrane channel, of a large
      cytoplasmic domain (CD) that features a balloon-like, water filled chamber
      opening to the cytoplasm through seven side pores and a small distal pore. The CD
      is apparently a molecular sieve covering the channel that optimizes loss of
      osmolytes during osmoadaptation. We employ diffusion theory and molecular
      dynamics simulations to explore the transport kinetics of Glu(-) and K(+) as
      representative osmolytes. We suggest that the CD indeed acts as a filter that
      actually balances passage of Glu(-) and K(+), and possibly other positive and
      negative osmolytes, to yield a largely neutral efflux and, thereby, reduce cell
      depolarization in the open state and conserve to a large degree the essential
      metabolite Glu(-).

PMID- 21723818
TI  - Membrane restructuring by phospholipase A2 is regulated by the presence of lipid
      domains.
AB  - Secretory phospholipase A(2) (sPLA(2)) catalyzes the hydrolysis of
      glycerophospholipids. This enzyme is sensitive to membrane structure, and its
      activity has been shown to increase in the presence of liquid-crystalline/gel
      (L(alpha)/L(beta)) lipid domains. In this work, we explore whether lipid domains
      can also direct the activity of the enzyme by inducing hydrolysis of certain
      lipid components due to preferential activity of the enzyme toward lipid domains
      susceptible to sPLA(2). Specifically, we show that the presence of
      L(alpha)/L(beta) and L(alpha)/P(beta') phase coexistence in a 1,2-dimyristoyl-sn
      glycero-3-phosphocholine (DMPC)/1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC)
      system results in the preferential hydrolysis of the shorter-chained lipid
      component in the mixture, leading to an enrichment in the longer-chained
      component. The restructuring process is monitored by atomic force microscopy on
      supported single and double bilayers formed by vesicle fusion. We observe that
      during preferential hydrolysis of the DMPC-rich L(alpha) regions, the L(beta) and
      P(beta') regions grow and reseal, maintaining membrane integrity. This result
      indicates that a sharp reorganization of the membrane structure can occur during
      sPLA(2) hydrolysis without necessarily destroying the membrane. We confirm by
      high-performance liquid chromatography the preferential hydrolysis of DMPC within
      the phase coexistence region of the DMPC/DSPC phase diagram, showing that this
      preferential hydrolysis is accentuated close to the solidus phase boundary.
      Differential scanning calorimetry results show that this preferential hydrolysis
      in the presence of lipid domains leads to a membrane system with a higher
      temperature melting profile due to enrichment in DSPC. Together, these results
      show that the presence of lipid domains can induce specificity in the hydrolytic
      activity of the enzyme, resulting in marked differences in the physical
      properties of the membrane end-product.

PMID- 21723819
TI  - Thermodynamic profiling of peptide membrane interactions by isothermal titration
      calorimetry: a search for pores and micelles.
AB  - Antimicrobial peptides are known to interact strongly with negatively charged
      lipid membranes, initially by peripheral insertion of the peptide into the
      bilayer, which for some antimicrobial peptides will be followed by pore
      formation, and successive solubilization of the membranes resulting in mixed
      peptide-lipid micelles. We have investigated the mode of action of the
      antimicrobial peptide mastoparan-X using isothermal titration calorimetry (ITC)
      and cryo-transmission electron microscopy (cryo-TEM). The results show that
      mastoparan-X induces a range of structural transitions of POPC/POPG (3:1) lipid
      membranes at different peptide/lipid ratios. It has been established that ITC can
      be used as a fast method for localizing membrane transitions and when combined
      with DLS and cryo-TEM can elucidate structural changes, including the threshold
      for pore formation and micellation. Cryo-TEM was employed to confirm the
      structural changes associated with the thermodynamic transitions found by ITC.
      The pore-formation process has furthermore been investigated in detail and the
      thermodynamic parameters of pore formation have been characterized using a system
      specific temperature where the enthalpy of peptide partitioning becomes zero
      (T(zero)). This allows for an exclusive study of the pore-formation process. The
      use of ITC to find T(zero) allows for characterization of the thermodynamic
      parameters of secondary processes on lipid membranes.

PMID- 21723820
TI  - Transfer of arginine into lipid bilayers is nonadditive.
AB  - Computer simulations suggest that the translocation of arginine through the
      hydrocarbon core of a lipid membrane proceeds by the formation of a water-filled
      defect that keeps the arginine molecule hydrated even at the center of the
      bilayer. We show here that adding additional arginine molecules into one of these
      water defects causes only a small change in free energy. The barrier for
      transferring multiple arginines through the membrane is approximately the same as
      for a single arginine and may even be lower depending on the exact geometry of
      the system. We discuss these results in the context of arginine-rich peptides
      such as antimicrobial and cell-penetrating peptides.

PMID- 21723821
TI  - Glycerol-induced membrane stiffening: the role of viscous fluid adlayers.
AB  - Lipid interfaces, ranging from cell membranes to thin surfactant layers that
      stabilize lung alveoli, are integral to living systems. Such interfaces are often
      subjected to mechanical forces, and because of their membrane-like geometry, they
      can easily deform by bending into localized folds. In this work, we explore the
      role of small molecules (i.e., glycerol) on the mechanical stability of model
      lung surfactant monolayers. We demonstrate that the presence of glycerol
      increases local monolayer bending stiffness by orders of magnitude. Our x-ray and
      neutron reflectivity measurements indicate that water is preferentially depleted,
      or glycerol is preferentially enriched, at the lipid headgroup/solvent interface,
      and that this glycerol-enriched layer extends O(10A) beneath the monolayer with
      an adsorption free energy of -2.5 to -4.6 kJ/mol. The dramatic change in membrane
      bending stiffness in the presence of the sugar adlayer is understood in terms of
      two models: 1), lipid antiplasticization by glycerol; and 2), a continuum
      mechanical model of the viscous adlayer.

PMID- 21723822
TI  - Influence of lipid membrane rigidity on properties of supporting polymer.
AB  - Temperature-sensitive hydrogel polymers are utilized as responsive layers in
      various applications. Although the polymer's native characteristics have been
      studied extensively, details concerning its properties during interaction with
      biorelated structures are lacking. This work investigates the interaction between
      a thermoresponsive polymer cushion and different lipid membrane capping layers
      probed by neutron reflectometry. N-isopropylacrylamide copolymerized with
      methacroylbenzophenone first supported a lipid bilayer composed of 1,2
      dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and subsequently 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The polymer-membrane systems were
      investigated above and below the polymer transition temperature (37 and 25
      degrees C). Although the same cushion supported each lipid membrane, the polymer
      hydration profile and thickness were markedly different for DPPE and DPPC
      systems. Because DPPE and DPPC have different bending rigidities, these results
      establish that the polymer-membrane interaction is critically mediated by the
      mechanics of the membrane, providing better insight into cell-hydrogel
      interactions.

PMID- 21723823
TI  - Gel-phase microdomains and lipid rafts in monolayers affect the redox properties
      of ubiquinone-10.
AB  - The redox properties of ubiquinone-10 (UQ) were examined in monolayers of
      mixtures of dioleoylphosphatidylcholine, palmitoylsphingomyelin, and cholesterol
      of different compositions, self-assembled on a mercury electrode, over the pH
      range from 7.5 to 9.5. A detailed analysis of the cyclic voltammograms of UQ in
      the above lipid environments points to a mechanism consisting of an elementary
      electron transfer step followed by two protonation (or deprotonation) steps in
      quasiequilibrium and by a further electron transfer step. In a lipid environment
      of solid-ordered (s(o)) microdomains in a liquid-disordered (l(d)) matrix,
      electron transport across the lipid monolayer takes place in the l(d) phase. In a
      pure s(o) phase, UQ tends to segregate into UQ-rich pools, exhibiting reversible
      electron transfer steps. In a lipid environment consisting of liquid-ordered
      (l(o)) microdomains (lipid rafts) in an l(d) matrix, UQ molecules tend to
      localize along the edge of the lipid rafts. However, in a lipid environment
      consisting exclusively of l(o) and s(o) microdomains, UQ molecules tend to
      segregate into UQ-rich pools. In all lipid environments, electron transport by UQ
      occurs with the quinone moiety localized on the solution side with respect to the
      ester linkages of the dioleoylphosphatidylcholine molecules.

PMID- 21723824
TI  - A physical model reveals the mechanochemistry responsible for dynein's processive
      motion.
AB  - The molecular motor dynein is associated with various cellular activities, such
      as directed transport along microtubules and the rhythmic beating of the axoneme.
      Because of the size and complexity of the protein, a detailed understanding of
      the mechanochemistry that drives dynein's processive motion is lacking. To
      overcome this deficiency, we developed the first (to our knowledge) computational
      model for two-headed dynein that couples conformational changes of the motor's
      subunits to the biochemical steps involved in ATP hydrolysis. Analysis of the
      model provides what we believe are several novel insights into how the protein
      functions: 1), structural constraints limit the motion of the free microtubule
      binding domain to one dimension, increasing the efficiency with which this domain
      finds a binding site; 2), in addition to the power stroke of the bound head,
      recovery of the free head to a pre-power-stroke conformation is required for this
      head to reach a forward binding site; 3), the order in which the power stroke and
      recovery transitions occur affects the probability of back-stepping; and 4), the
      existence of multiple equilibria in the motor's bending energy provides a
      mechanism for processive back-stepping. To the best of our knowledge, our
      computational model provides the first complete mechanochemical description of
      the motor protein dynein, and the findings presented here should motivate new
      experimental investigations to test its predictions.

PMID- 21723825
TI  - Cofilin-linked changes in actin filament flexibility promote severing.
AB  - The actin regulatory protein, cofilin, increases the bending and twisting
      elasticity of actin filaments and severs them. It has been proposed that
      filaments partially decorated with cofilin accumulate stress from thermally
      driven shape fluctuations at bare (stiff) and decorated (compliant) boundaries,
      thereby promoting severing. This mechanics-based severing model predicts that
      changes in actin filament compliance due to cofilin binding affect severing
      activity. Here, we test this prediction by evaluating how the severing activities
      of vertebrate and yeast cofilactin scale with the flexural rigidities determined
      from analysis of shape fluctuations. Yeast actin filaments are more compliant in
      bending than vertebrate actin filaments. Severing activities of cofilactin
      isoforms correlate with changes in filament flexibility. Vertebrate cofilin binds
      but does not increase the yeast actin filament flexibility, and does not sever
      them. Imaging of filament thermal fluctuations reveals that severing events are
      associated with local bending and fragmentation when deformations attain a
      critical angle. The critical severing angle at boundaries between bare and
      cofilin-decorated segments is smaller than in bare or fully decorated filaments.
      These measurements support a cofilin-severing mechanism in which mechanical
      asymmetry promotes local stress accumulation and fragmentation at boundaries of
      bare and cofilin-decorated segments, analogous to failure of some nonprotein
      materials.

PMID- 21723826
TI  - DNA sequence correlations shape nonspecific transcription factor-DNA binding
      affinity.
AB  - Transcription factors (TFs) are regulatory proteins that bind DNA in promoter
      regions of the genome and either promote or repress gene expression. Here, we
      predict analytically that enhanced homooligonucleotide sequence correlations,
      such as poly(dA:dT) and poly(dC:dG) tracts, statistically enhance nonspecific TF
      DNA binding affinity. This prediction is generic and qualitatively independent of
      microscopic parameters of the model. We show that nonspecific TF binding affinity
      is universally controlled by the strength and symmetry of DNA sequence
      correlations. We perform correlation analysis of the yeast genome and show that
      DNA regions highly occupied by TFs exhibit stronger homooligonucleotide sequence
      correlations, and thus a higher propensity for nonspecific binding, than do
      poorly occupied regions. We suggest that this effect plays the role of an
      effective localization potential that enhances quasi-one-dimensional diffusion of
      TFs in the vicinity of DNA, speeding up the stochastic search process for
      specific TF binding sites. The effect is also predicted to impose an upper bound
      on the size of TF-DNA binding motifs.

PMID- 21723827
TI  - Ensemble of secondary structures for encapsidated satellite tobacco mosaic virus
      RNA consistent with chemical probing and crystallography constraints.
AB  - Viral genomic RNA adopts many conformations during its life cycle as the genome
      is replicated, translated, and encapsidated. The high-resolution crystallographic
      structure of the satellite tobacco mosaic virus (STMV) particle reveals 30
      helices of well-ordered RNA. The crystallographic data provide global constraints
      on the possible secondary structures for the encapsidated RNA. Traditional free
      energy minimization methods of RNA secondary structure prediction do not generate
      structures consistent with the crystallographic data, and to date no complete
      STMV RNA basepaired secondary structure has been generated. RNA-protein
      interactions and tertiary interactions may contribute a significant degree of
      stability, and the kinetics of viral assembly may dominate the folding process.
      The computational tools, Helix Find & Combine, Crumple, and Sliding Windows and
      Assembly, evaluate and explore the possible secondary structures for encapsidated
      STMV RNA. All possible hairpins consistent with the experimental data and a
      cotranscriptional folding and assembly hypothesis were generated, and the
      combination of hairpins that was most consistent with experimental data is
      presented as the best representative structure of the ensemble. Multiple
      solutions to the genome packaging problem could be an evolutionary advantage for
      viruses. In such cases, an ensemble of structures that share favorable global
      features best represents the RNA fold.

PMID- 21723828
TI  - Salt contribution to RNA tertiary structure folding stability.
AB  - Accurate quantification of the ionic contribution to RNA folding stability could
      greatly enhance our ability to understand and predict RNA functions. Recently,
      motivated by the potential importance of ion correlation and fluctuation in RNA
      folding, we developed the tightly bound ion (TBI) model. Extensive experimental
      tests showed that the TBI model can lead to better treatment of multivalent ions
      than the Poisson-Boltzmann equation. In this study, we use the model to quantify
      the contribution of salt (Na(+) and Mg(2+)) to the RNA tertiary structure folding
      free energy. Folding of the RNA tertiary structure often involves intermediates.
      We focus on the folding transition from an intermediate state to the native
      state, and compute the electrostatic folding free energy of the RNA. Based on
      systematic calculations for a variety of RNA molecules, we derive a set of
      formulas for the electrostatic free energy for tertiary structural folding as a
      function of the sequence length and compactness of the RNA and the Na(+) and
      Mg(2+) concentrations. Extensive comparisons with experimental data suggest that
      our model and the extracted empirical formulas are quite reliable.

PMID- 21723829
TI  - Torque generation in F1-ATPase devoid of the entire amino-terminal helix of the
      rotor that fills half of the stator orifice.
AB  - F(1)-ATPase is an ATP-driven rotary molecular motor in which the central gamma
      subunit rotates inside a cylinder made of alpha(3)beta(3) subunits. The amino and
      carboxyl termini of the gamma rotor form a coiled coil of alpha-helices that
      penetrates the stator cylinder to serve as an axle. Crystal structures indicate
      that the axle is supported by the stator at two positions, at the orifice and by
      the hydrophobic sleeve surrounding the axle tip. The sleeve contacts are almost
      exclusively to the longer carboxyl-terminal helix, whereas nearly half the
      orifice contacts are to the amino-terminal helix. Here, we truncated the amino
      terminal helix stepwise up to 50 residues, removing one half of the axle all the
      way up and far beyond the orifice. The half-sliced axle still rotated with an
      unloaded speed a quarter of the wild-type speed, with torque nearly half the wild
      type torque. The truncations were made in a construct where the rotor tip was
      connected to a beta-subunit via a short peptide linker. Linking alone did not
      change the rotational characteristics significantly. These and previous results
      show that nearly half the normal torque is generated if rotor-stator interactions
      either at the orifice or at the sleeve are preserved, suggesting that the make of
      the motor is quite robust.

PMID- 21723830
TI  - A direct coupling between global and internal motions in a single domain protein?
      MD investigation of extreme scenarios.
AB  - Proteins are not rigid molecules, but exhibit internal motions on timescales
      ranging from femto- to milliseconds and beyond. In solution, proteins also
      experience global translational and rotational motions, sometimes on timescales
      comparable to those of the internal fluctuations. The possibility that internal
      and global motions may be directly coupled has intriguing implications, given
      that enzymes and cell signaling proteins typically associate with binding
      partners and cellular scaffolds. Such processes alter their global motion and may
      affect protein function. Here, we present molecular dynamics simulations of
      extreme case scenarios to examine whether a possible relationship exists. In our
      model protein, a ubiquitin-like RhoGTPase binding domain of plexin-B1, we removed
      either internal or global motions. Comparisons with unrestrained simulations show
      that internal and global motions are not appreciably coupled in this single
      domain protein. This lack of coupling is consistent with the observation that the
      dynamics of water around the protein, which is thought to permit, if not
      stimulate, internal dynamics, is also largely independent of global motion. We
      discuss implications of these results for the structure and function of proteins.

PMID- 21723831
TI  - Rapid assembly and collective behavior of microtubule bundles in the presence of
      polyamines.
AB  - Microtubules (MTs) are cylindrical cytoskeleton polymers composed of alpha-beta
      tubulin heterodimers whose dynamic properties are essential to fulfill their
      numerous cellular functions. In response to spatial confinement, dynamic MTs,
      even in the absence of protein partners, were shown to self-organize into higher
      order structures (spindle or striped structures) which lead to interesting
      dynamical properties (MT oscillations). In this study, we considered the assembly
      and sensitivity of dynamic MTs when in bundles. To perform this study, spermine,
      a natural tetravalent polyamine present at high concentrations in all eukaryote
      cells, was used to trigger MT bundling while preserving MT dynamics.
      Interestingly, we first show that, near physiological ionic strengths, spermine
      promotes the bundling of MTs whereas it does not lead to aggregation of free
      tubulin, which would have been detrimental to MT polymerization. Experimental and
      theoretical results also indicate that, to obtain a high rate of bundle assembly,
      bundling should take place at the beginning of assembly when rapid rotational
      movements of short and newly nucleated MTs are still possible. On the other hand,
      the bundling process is significantly slowed down for long MTs. Finally, we found
      that short MT bundles exhibit a higher sensitivity to cold exposure than do
      isolated MTs. To account for this phenomenon, we suggest that a collective
      behavior takes place within MT bundles because an MT entering into a phase of
      shortening could increase the probability of the other MTs in the same bundle to
      enter into shortening phase due to their close proximity. We then elaborate on
      some putative applications of our findings to in vivo conditions including
      neurons.

PMID- 21723832
TI  - How do thermophilic proteins and proteomes withstand high temperature?
AB  - We attempt to understand the origin of enhanced stability in thermophilic
      proteins by analyzing thermodynamic data for 116 proteins, the largest data set
      achieved to date. We compute changes in entropy and enthalpy at the convergence
      temperature where different driving forces are maximally decoupled, in contrast
      to the majority of previous studies that were performed at the melting
      temperature. We find, on average, that the gain in enthalpy upon folding is lower
      in thermophiles than in mesophiles, whereas the loss in entropy upon folding is
      higher in mesophiles than in thermophiles. This implies that entropic
      stabilization may be responsible for the high melting temperature, and hints at
      residual structure or compactness of the denatured state in thermophiles. We find
      a similar trend by analyzing a homologous set of proteins classified based only
      on the optimum growth temperature of the organisms from which they were
      extracted. We find that the folding free energy at the temperature of maximal
      stability is significantly more favorable in thermophiles than in mesophiles,
      whereas the maximal stability temperature itself is similar between these two
      classes. Furthermore, we extend the thermodynamic analysis to model the entire
      proteome. The results explain the high optimal growth temperature in thermophilic
      organisms and are in excellent quantitative agreement with full thermal growth
      rate data obtained in a dozen thermophilic and mesophilic organisms.

PMID- 21723833
TI  - Thermal denaturation studies of collagen by microthermal analysis and atomic
      force microscopy.
AB  - The structural properties of collagen have been the subject of numerous studies
      over past decades, but with the arrival of new technologies, such as the atomic
      force microscope and related techniques, a new era of research has emerged. Using
      microthermal analysis, it is now possible to image samples as well as performing
      localized thermal measurements without damaging or destroying the sample itself.
      This technique was successfully applied to characterize the thermal response
      between native collagen fibrils and their denatured form, gelatin. Thermal
      transitions identified at (150 +/- 10) degrees C and (220 +/- 10) degrees C can
      be related to the process of gelatinization of the collagen fibrils, whereas at
      higher temperatures, both the gelatin and collagen samples underwent two-stage
      transitions with a common initial degradation temperature at (300 +/- 10) degrees
      C and a secondary degradation temperature of (340 +/- 10) degrees C for the
      collagen and of (420 +/- 10) degrees C for the gelatin, respectively. The
      broadening and shift in the secondary degradation temperature was linked to the
      spread of thermal degradation within the gelatin and collagen fibrils matrix
      further away from the point of contact between probe and sample. Finally, similar
      measurements were performed inside a bone resorption lacuna, suggesting that
      microthermal analysis is a viable technique for investigating the
      thermomechanical response of collagen for in situ samples that would be,
      otherwise, too challenging or not possible using bulk techniques.

PMID- 21723834
TI  - Measuring the rate of conjugal plasmid transfer in a bacterial population using
      quantitative PCR.
AB  - Horizontal transfer of genes between species is an important mechanism for
      bacterial genome evolution. In Escherichia coli, conjugation is the transfer from
      a donor (F(+)) to a recipient (F(-)) cell through cell-to-cell contact. We
      demonstrate what we believe to be a novel qPCR method for quantifying the
      transfer kinetics of the F plasmid in a population by enumerating the relative
      abundance of genetic loci unique to the plasmid and the chromosome. This approach
      allows us to query the plasmid transfer rate without the need for selective
      culturing with unprecedented single locus resolution. We fit the results to a
      mass action model where the rate of plasmid growth includes the lag time of newly
      formed F(+) transconjugants and the recovery time between successive conjugation
      events of the F(+) donors. By assaying defined mixtures of genotypically
      identical donor and recipient cells at constant inoculation densities, we extract
      an F plasmid transfer rate of 5 * 10(-10) (cells/mL . min)(-1). We confirm a
      plasmid/chromosome ratio of 1:1 in homogenous F(+) populations throughout batch
      growth. Surprisingly, in some mixture experiments we observe an excess of F
      plasmid in the early saturation phase that equilibrates to a final ratio of one
      plasmid per chromosome.

PMID- 21723835
TI  - Label-free critical micelle concentration determination of bacterial quorum
      sensing molecules.
AB  - A practical label-free method for the rapid determination of small-molecule
      critical micelle concentration (CMC) using a fixed-angle light-scattering
      technique is described. Change in 90 degrees  light scattering at a fixed
      wavelength of incident radiation with increasing bacterial quorum molecule
      concentration and the observation of a break point is used to determine CMC. In
      our study, this technique is utilized to investigate the aqueous CMC of
      previously uncharacterized Pseudomonas aeruginosa quorum sensing signaling
      molecules (QSSM) belonging to the n-acylhomoserine lactone and 2-alkyl-4
      quinolone classes. Several were found to form micelles within a physiologically
      relevant concentration range and potential roles of these micelles as QSSM
      transporters are discussed. The influence of temperature and the presence of
      biological membranes or serum proteins on QSSM CMC are also investigated and
      evidence is obtained to suggest the QSSMs studied are capable of both membrane
      and serum protein interaction. This demonstrates that the fixed-angle light
      scattering technique outlined can be used simply and rapidly to determine small
      molecule CMC under a variety of conditions.

PMID- 21723836
TI  - Hindered diffusion in polymeric solutions studied by fluorescence correlation
      spectroscopy.
AB  - Diffusion of molecules in the crowded and charged interior of the cell has long
      been of interest for understanding cellular processes. Here, we introduce a model
      system of hindered diffusion that includes both crowding and binding. In
      particular, we obtained the diffusivity of the positively charged protein,
      ribonuclease A (RNase), in solutions of dextrans of various charges (binding) and
      concentrations (crowding), as well as combinations of both, in a buffer of
      physiological ionic strength. Using fluorescence correlation spectroscopy, we
      observed that the diffusivity of RNase was unaffected by the presence of
      positively charged or neutral dextrans in the dilute regime but was affected by
      crowding at higher polymer concentrations. Conversely, protein diffusivity was
      significantly reduced by negatively charged dextrans, even at 0.4 MUM (0.02% w/v)
      dextran. The diffusivity of RNase decreased with increasing concentrations of
      negative dextran, and the amount of bound RNase increased until it reached a
      plateau of ~80% bound RNase. High salt concentrations were used to establish the
      electrostatic nature of the binding. Binding of RNase to the negatively charged
      dextrans was further confirmed by ultrafiltration.

PMID- 21723837
TI  - Pathways of liver injury in alcoholic liver disease.

PMID- 21723838
TI  - Biological or relational screening for liver disease?

PMID- 21723839
TI  - Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in
      adults: a systematic review.
AB  - Non-alcoholic fatty liver disease is a serious and growing clinical problem.
      Despite lifestyle modification, i.e. diet and physical activity, being the
      recommended therapy, there are currently no systematic evaluations of its
      efficacy. This review applies a systematic approach to evaluating lifestyle
      modifications studied to date. Medline (Pubmed), Scopus, and the Cochrane
      Controlled Trials Register were searched for studies and study groups assessing
      the effect of diet, physical activity, and/or exercise modification in adult
      populations with non-alcoholic fatty liver disease. The outcome markers of
      interest were indicators of steatosis, histological evidence of inflammation and
      fibrosis, and glucose control/insulin sensitivity. We identified 23 studies for
      inclusion; seven had control groups, but only six were randomised. Eleven groups
      received diet-only interventions, two exercise-only, and 19 diet and physical
      activity/exercise. Studies consistently showed reductions in liver fat and/or
      liver aminotransferase concentration, with the strongest correlation being with
      weight reduction. Of the 5 studies reporting changes in histopathology, all
      showed a trend towards reduction in inflammation, in 2 this was statistically
      significant. Changes in fibrosis were less consistent with only one study showing
      a significant reduction. The majority of studies also reported improvements in
      glucose control/insulin sensitivity following intervention. However, study
      design, definition of disease, assessment methods, and interventions varied
      considerably across studies. Lifestyle modifications leading to weight reduction
      and/or increased physical activity consistently reduced liver fat and improved
      glucose control/insulin sensitivity. Limited data also suggest that lifestyle
      interventions may hold benefits for histopathology.

PMID- 21723840
TI  - A sprint to increase response to HCV treatment: expectancies but caution.

PMID- 21723841
TI  - Activation of unfolded protein response and autophagy during HCV infection
      modulates innate immune response.
AB  - Autophagy, a process for catabolizing cytoplasmic components, has been implicated
      in the modulation of interactions between RNA viruses and their host. However,
      the mechanism underlying the functional role of autophagy in the viral life cycle
      still remains unclear. Hepatitis C virus (HCV) is a single-stranded, positive
      sense, membrane-enveloped RNA virus that can cause chronic liver disease. Here we
      report that HCV induces the unfolded protein response (UPR), which in turn
      activates the autophagic pathway to promote HCV RNA replication in human hepatoma
      cells. Further analysis revealed that the entire autophagic process through to
      complete autolysosome maturation was required to promote HCV RNA replication and
      that it did so by suppressing innate antiviral immunity. Gene silencing or
      activation of the UPR-autophagy pathway activated or repressed, respectively, IFN
      beta activation mediated by an HCV-derived pathogen-associated molecular pattern
      (PAMP). Similar results were achieved with a PAMP derived from Dengue virus
      (DEV), indicating that HCV and DEV may both exploit the UPR-autophagy pathway to
      escape the innate immune response. Taken together, these results not only define
      the physiological significance of HCV-induced autophagy, but also shed light on
      the knowledge of host cellular responses upon HCV infection as well as on
      exploration of therapeutic targets for controlling HCV infection.

PMID- 21723843
TI  - Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and
      represses pro-survival XBP1 signaling in human multiple myeloma cells.
AB  - OBJECTIVE: Resveratrol, trans-3, 4', 5,-trihydroxystilbene, suppresses multiple
      myeloma (MM). The endoplasmic reticulum (ER) stress response component inositol
      requiring enzyme 1alpha (IRE1alpha)/X-box binding protein 1 (XBP1) axis is
      essential for MM pathogenesis. We investigated the molecular action of
      resveratrol on IRE1alpha/XBP1 axis in human MM cells. MATERIALS AND METHODS:
      Human MM cell lines ANBL-6, OPM2, and MM.1S were utilized to determine the
      molecular signaling events following treatment with resveratrol. The stimulation
      of IRE1alpha/XBP1 axis was analyzed by Western blot and reverse transcription
      polymerase chain reaction. The effect of resveratrol on the transcriptional
      activity of spliced XBP1 was assessed by luciferase assays. Chromatin
      immunoprecipitation was performed to determine the effects of resveratrol on the
      DNA binding activity of XBP1 in MM cells. RESULTS: Resveratrol activated
      IRE1alpha as evidenced by XBP1 messenger RNA splicing and phosphorylation of both
      IRE1alpha and its downstream kinase c-Jun N-terminal kinase in MM cells. These
      responses were associated with resveratrol-induced cytotoxicity of MM cells.
      Resveratrol selectively suppressed the transcriptional activity of XBP1s while it
      stimulated gene expression of the molecules that are regulated by the non
      IRE1/XBP1 axis of the ER stress response. Luciferase assays indicated that
      resveratrol suppressed the transcriptional activity of XBP1s through sirtuin 1, a
      downstream molecular target of resveratrol. Chromatin immunoprecipitation studies
      revealed that resveratrol decreased the DNA binding capacity of XBP1 and
      increased the enrichment of sirtuin 1 at the XBP1 binding region in the XBP1
      promoter. CONCLUSIONS: Resveratrol exerts its chemotherapeutic effect on human MM
      cells through mechanisms involving the impairment of the pro-survival XBP1
      signaling and the activation of pro-apoptotic ER stress response.

PMID- 21723844
TI  - Relative contribution of changes in sodium current versus intercellular coupling
      on reentry initiation in 2-dimensional preparations of plakophilin-2-deficient
      cardiac cells.
AB  - BACKGROUND: Loss of expression of the desmosomal protein plakophilin-2 (PKP2)
      leads to decreased gap junction-mediated (GJ) coupling, and alters the amplitude
      and kinetics of sodium current in cardiac myocytes. Whether these modifications,
      alone or in combination, are sufficient to act as arrhythmogenic substrates
      remains undefined. OBJECTIVE: This study sought to characterize arrhythmia
      susceptibility and reentry dynamics consequent to loss of PKP2 expression, and to
      assess the relative contribution of cell uncoupling versus alterations in sodium
      current in generation of reentry. METHODS: Monolayers of neonatal rat ventricular
      myocytes were treated with oligonucleotides that either prevented or failed to
      prevent PKP2 expression. Numerical simulations modeled experimentally observed
      modifications in I(Na), GJ coupling, or both (models PKP2-Na, PKP2-GJ, and PKP2
      KD, respectively). Relative roles of sodium current density versus kinetics were
      further explored. RESULTS: Loss of PKP2 expression increased incidence of rotors
      and decreased frequency of rotation. Mathematical simulations revealed that
      single premature stimuli initiated rotors in models PKP2-Na and PKP2-KD, but not
      PKP2-GJ. Changes in sodium current kinetics, rather than current density, were
      key to reentry initiation. Anatomical barriers led to vortex shedding,
      wavebreaks, and rotors when I(Na) kinetics, but not GJ coupling or I(Na) density,
      were altered. CONCLUSION: PKP2-dependent changes in sodium current kinetics lead
      to slow conduction, increased propensity to functional block, and vortex
      shedding. Changes in GJ or I(Na) density played only a minor role on reentry
      susceptibility. Changes in electrical properties of the myocyte caused by loss of
      expression of PKP2 can set the stage for rotors even if anatomical homogeneity is
      maintained.

PMID- 21723845
TI  - Left-to-right ventricular differences in I(KATP) underlie epicardial
      repolarization gradient during global ischemia.
AB  - BACKGROUND: The ionic mechanisms of electrical heterogeneity in the ischemic
      ventricular epicardium remain poorly understood. OBJECTIVE: This study sought to
      test the hypothesis that the adenosine triphosphate (ATP)-activated K+ current
      (I(KATP)) plays an important role in mediating repolarization differences between
      the right ventricle (RV) and left ventricle (LV) during global ischemia. METHODS:
      Electrical activity in Langendorff-perfused guinea pig hearts was recorded
      optically during control, ischemia, and reperfusion. Patch-clamp experiments were
      used to quantify I(KATP) density in isolated myocytes. Molecular correlates of
      I(KATP) (Kir6/SUR) were probed via reverse transcriptase-polymerase chain
      reaction. The role of I(KATP) in modulating repolarization was studied using
      computer simulations. RESULTS: Action potential duration (APD) was similar
      between LV and RV in control hearts, but significantly different in global
      ischemia. Pretreatment of hearts with 10 MUM glibenclamide (I(KATP) blocker)
      abolished the APD gradient during ischemia. In the absence of ischemia, pinacidil
      (I(KATP) opener) tended to shorten the APD more in the LV, and caused a small but
      significant increase in APD dispersion. In voltage clamp experiments, the density
      of the whole-cell current activated by pinacidil at depolarized potentials was
      significantly larger in LV, compared with RV epicardial myocytes. The mRNA levels
      of Kir6.1/Kir6.2 were significantly higher in LV compared with RV. Simulations
      showed that I(KATP) is the main determinant of LV-RV APD gradient, whereas cell
      to-cell coupling modified the spatial distribution of this APD gradient.
      CONCLUSION: I(KATP) is an important determinant of the epicardial LV-RV APD
      gradient during global ischemia, in part due to a higher current density and
      molecular expression in the LV.

PMID- 21723846
TI  - Serpin peptidase inhibitor clade A member 1 (SerpinA1) is a novel biomarker for
      progression of cutaneous squamous cell carcinoma.
AB  - The incidence of keratinocyte-derived nonmelanoma skin cancers is increasing
      worldwide because of cumulative recreational exposure to sunlight. At present, no
      specific molecular markers are available for assessing the progression of
      premalignant actinic keratoses to invasive cutaneous squamous cell carcinoma
      (SCC). We examined the role of the Serpin family in skin SCCs. Expression
      profiling of cutaneous SCC cell lines (n = 8) revealed up-regulation of SerpinA1
      compared with normal epidermal keratinocytes (n = 5). Analysis with quantitative
      RT-PCR showed that the mean level of SerpinA1 mRNA was markedly up-regulated in
      cutaneous SCC cell lines (n = 8) compared with in normal keratinocytes. SerpinA1
      production by SCC cells was dependent on p38 mitogen-activated protein kinase
      activity and was up-regulated by epidermal growth factor, tumor necrosis factor
      alpha, interferon-gamma, and IL-1beta. Immunostaining of tissue arrays with 148
      human tissue samples revealed tumor cell-associated expression of SerpinA1 in 19
      of 36 actinic keratoses, 22 of 29 Bowen's disease samples, 67 of 71 sporadic
      SCCs, and all 12 recessive dystrophic epidermolysis bullosa-associated SCCs
      examined. Moreover, tumor cell-associated SerpinA1 staining was detected in all
      chemically induced mouse skin SCCs studied (n = 17). Overexpression of SerpinA1
      mRNA was also detected by quantitative RT-PCR in chemically induced mouse skin
      SCCs (n = 14) compared with control tissues (n = 14). These data identify
      SerpinA1 as a novel tumor cell-associated biomarker for progression of cutaneous
      SCCs.

PMID- 21723847
TI  - Low-density lipoprotein density determination by electric conductivity.
AB  - The predominance of small dense low-density lipoprotein (LDL) particles is
      associated with an increased risk of coronary heart disease. A simple but precise
      method has been developed, based on electrical conductivity of an isopycnic
      gradient of KBr, to obtain density values of human LDL fraction. The results
      obtained can distinguish LDL density populations and their subfractions from
      different patients. These data were corroborated by Fourier transform infrared
      spectroscopy (FTIR) (structure) and light-scattering analyses (size).

PMID- 21723848
TI  - Isolation of detergent-resistant membranes from plant photosynthetic and non
      photosynthetic tissues.
AB  - Microdomains, or lipid rafts, are transient membrane regions enriched in
      sphingolipids and sterols that have only recently, but intensively, been studied
      in plants. In this work, we report a detailed, easy-to-follow, and fast procedure
      to isolate detergent-resistant membranes (DRMs) from purified plasma membranes
      (PMs) that was used to obtain DRMs from Phaseolus vulgaris and Nicotiana tabacum
      leaves and germinating Zea mays embryos. Characterized according to yield,
      ultrastructure, and sterol composition, these DRM preparations showed
      similarities to analogous preparations from other eukaryotic cells. Isolation of
      DRMs from germinating maize embryos reveals the presence of microdomains at very
      early developmental stages of plants.

PMID- 21723849
TI  - Characterization of nitrated phenolic compounds for their anti-oxidant, pro
      oxidant, and nitration activities.
AB  - Coffee is one of the most widely consumed beverages worldwide. Evidence of the
      health benefits and the important contribution of coffee brew to the intake of
      anti-oxidants in the diet has increased coffee consumption. Chlorogenic acid
      (ChA) and caffeic acid (CaA) are the major phenolic compounds in coffee. However,
      phenolic compounds, which are generally effective anti-oxidants, can become pro
      oxidants in the presence of Cu(2+) to induce DNA damage under certain conditions.
      On the other hand, sodium nitrite (NaNO(2)) is widely used as a food additive to
      preserve and tinge color on cured meat and fish. It is possible that phenolic
      compounds react with NaNO(2) under acidic conditions, such as gastric juice. In
      this study, we identified compounds produced by the reaction between ChA or CaA
      in coffee and NaNO(2) in artificial gastric juice. The identified phenolic
      compounds and nitrated phenolic compounds were assessed for their anti-oxidant,
      pro-oxidant, and nitration activities by performing an in vitro assay. The
      nitrated phenolic compounds seemed to show increased anti-oxidant activity and
      decreased pro-oxidant activity. However, one nitrated CaA compound that has a
      furoxan ring showed the ability to release NO(2)(-) in the neutral condition.

PMID- 21723850
TI  - Reduced expression of Tis7/IFRD1 protein in murine and human cystic fibrosis
      airway epithelial cell models homozygous for the F508del-CFTR mutation.
AB  - 12-O-tetradecanoyl phorbol-13-acetate-induced sequence 7/interferon related
      development regulator 1 (Tis7/IFRD1) has been recently identified as a modifier
      gene in lung inflammatory disease severity in patients with cystic fibrosis (CF),
      based upon its capacity to regulate inflammatory activities in neutrophils. In CF
      patients, the F508del mutation in the Cftr gene encoding a chloride channel, the
      CF transmembrane conductance regulator (CFTR) in airway epithelial cells results
      in an exaggerated inflammatory response of these cells. At present, it is unknown
      whether the Tis7/IFRD1 gene product is expressed in airway epithelial cells. We
      therefore investigated the possibility there is an intrinsic alteration in
      Tis7/IFRD1 protein level in cells lacking CFTR function in tracheal homogenates
      of F508del-CFTR mice and in a F508del-CFTR human bronchial epithelial cell line
      (CFBE41o(-) cells). When Tis7/IFRD1 protein was detectable, trachea from F508del
      CFTR mice showed a reduction in the level of Tis7/IFRD1 protein compared to wild
      type control littermates. A significant reduction of IFRD1 protein level was
      found in CFBE41o(-) cells compared to normal bronchial epithelial cells 16HBE14o(
      ). Surprisingly, messenger RNA level of IFRD1 in CFBE41o(-) cells was found
      elevated. Treating CFBE41o(-) cells with the antioxidant glutathione rescued the
      IFRD1 protein level closer to control level and also reduced the pro-inflammatory
      cytokine IL-8 release. This work provides evidence for the first time of reduced
      level of IFRD1 protein in murine and human F508del-CFTR airway epithelial cell
      models, possibly mediated in response to oxidative stress which might contribute
      to the exaggerated inflammatory airway response observed in CF patients
      homozygous for the F508del mutation.

PMID- 21723851
TI  - Enzymatic characterization of Catalase from Bacillus anthracis and prediction of
      critical residues using information theoretic measure of Relative Entropy.
AB  - In order to cope up with the reactive oxygen species (ROS) generated by host
      innate immune response, most of the intracellular organisms express Catalase for
      the enzymatic destruction/detoxification of hydrogen peroxide, to combat its
      deleterious effects. Catalase thus, scavenges ROS thereby playing a pivotal role
      in facilitating the survival of the pathogen within the host, and thus
      contributes to its pathogenesis. Bacillus anthracis harbors five isoforms of
      Catalase, but none of them has been studied so far. Thus, this study is the first
      attempt to delineate the biochemical and functional characteristics of one of the
      isoforms of Catalase (Cat1.4) of B. anthracis, followed by identification of
      residues critical for catalysis. The general strategy used, so far for mutational
      analysis in Catalases is structure based, i.e. the residues in the vicinity of
      heme were mutated to decipher the enzymatic mechanism. However, in the present
      study, protein sequence analysis was used for the prediction of catalytically
      important residues of Catalase. Essential measures were adopted to ensure the
      accuracy of predictions like after retrieval of well-annotated sequences from the
      database with EC 1.11.1.6, preprocessing was done to remove irrelevant sequences.
      The method used for multiple alignment of sequences, was guided by structural
      alignment and thereafter, an information theoretic measure, Relative Entropy was
      used for the critical residue prediction. By exploiting this strategy, we
      identified two previously known essential residues, H55 and Y338 in the active
      site which were demonstrated to be crucial for the activity. We also identified
      six novel crucial residues (Q332, Y117, H215, W257, N376 and H146) located
      distantly from the active site. Thus, the present study highlights the
      significance of this methodology to identify not only those crucial residues
      which lie in the active site of Catalase, but also the residues located
      distantly.

PMID- 21723852
TI  - The adaptor Lnk (SH2B3): an emerging regulator in vascular cells and a link
      between immune and inflammatory signaling.
AB  - A better knowledge of the process by which inflammatory extracellular signals are
      relayed from the plasma membrane to specific intracellular sites is a key step to
      understand how inflammation develops and how it is regulated. This review focuses
      on Lnk (SH2B3) a member, with SH2B1 and SH2B2, of the SH2B family of adaptor
      proteins that influences a variety of signaling pathways mediated by Janus kinase
      and receptor tyrosine kinases. SH2B adaptor proteins contain conserved
      dimerization, pleckstrin homology, and SH2 domains. Initially described as a
      regulator of hematopoiesis and lymphocyte differentiation, Lnk now emerges as a
      key regulator in hematopoeitic and non hematopoeitic cells such as endothelial
      cells (EC) moderating growth factor and cytokine receptor-mediated signaling. In
      EC, Lnk is a negative regulator of TNF signaling that reduce proinflammatory
      phenotype and prevent EC from apoptosis. Lnk is a modulator in integrin signaling
      and actin cytoskeleton organization in both platelets and EC with an impact on
      cell adhesion, migration and thrombosis. In this review, we discuss some recent
      insights proposing Lnk as a key regulator of bone marrow-endothelial progenitor
      cell kinetics, including the ability to cell growth, endothelial commitment,
      mobilization, and recruitment for vascular regeneration. Finally, novel findings
      also provided evidences that mutations in Lnk gene are strongly linked to
      myeloproliferative disorders but also autoimmune and inflammatory syndromes where
      both immune and vascular cells display a role. Overall, these studies emphasize
      the importance of the Lnk adaptor molecule not only as prognostic marker but also
      as potential therapeutic target.

PMID- 21723853
TI  - Hyperoxia attenuates the inhibitory effect of nitric oxide donors on HIF prolyl-4
      hydroxylase-2: Implication on discriminative effect of nitric oxide on HIF prolyl
      4-hydroxylase-2 and collagen prolyl-4-hydroxylase.
AB  - Prolyl 4-hydroxylases (P4Hs), such as collagen prolyl-4-hydroxylases (CPHs) and
      hypoxia inducible factor prolyl-4-hydroxylases (HPHs), have recently been
      recognized as promising drug targets for the treatment of fibrotic and ischemic
      diseases. CPHs and HPHs catalyze identical metabolic reactions, yet lead to quite
      different physiological consequences, collagen synthesis and the regulation of
      oxygen homeostasis. Selective modulation of the two enzymes should provide a
      therapeutic benefit upon pharmacotherapy. In an in vitro VHL capture assay,
      hydroxylation of the 19mer HIF peptide (corresponding to HIF-1alpha residues 556
      574) by HPH-2 was effectively prevented by nitric oxide (NO) donors, (+/-)-S
      nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione. The NO donors also
      caused inhibition of HPHs and accumulation of nonhydroxylated HIF-1alpha protein
      in A549 human lung adenocarcinoma cells. Hyperoxia (100% O(2)) attenuated both NO
      donor-induced accumulation of HIF-1alpha and inhibition of HPH-mediated
      hydroxylation. In the presence of a proteasome inhibitor, MG132, the hyperoxia
      mediated degradation of HIF-1alpha was deterred and hydroxylated HIF-1alpha was
      detected. SNAP, while being an effective inhibitor of proline 4-hydroxylation of
      HIF-1alpha by HPH-2, did not diminish proline hydroxylation of collagen by CPHs.
      Our data suggest that NO inhibits HPH-2 via competing with dioxygen and that the
      discriminative effect of NO on CPHs and HPH-2 is attributable to the difference
      in the affinity of the two enzymes toward dioxygen.

PMID- 21723855
TI  - Preparation of human drug metabolites using fungal peroxygenases.
AB  - The synthesis of hydroxylated and O- or N-dealkylated human drug metabolites
      (HDMs) via selective monooxygenation remains a challenging task for synthetic
      organic chemists. Here we report that aromatic peroxygenases (APOs; EC 1.11.2.1)
      secreted by the agaric fungi Agrocybe aegerita and Coprinellus radians catalyzed
      the H2O2-dependent selective monooxygenation of diverse drugs, including
      acetanilide, dextrorphan, ibuprofen, naproxen, phenacetin, sildenafil and
      tolbutamide. Reactions included the hydroxylation of aromatic rings and aliphatic
      side chains, as well as O- and N-dealkylations and exhibited different
      regioselectivities depending on the particular APO used. At best, desired HDMs
      were obtained in yields greater than 80% and with isomeric purities up to 99%.
      Oxidations of tolbutamide, acetanilide and carbamazepine in the presence of
      H218O2 resulted in almost complete incorporation of 18O into the corresponding
      products, thus establishing that these reactions are peroxygenations. The
      deethylation of phenacetin-d1 showed an observed intramolecular deuterium isotope
      effect [(k(H)/k(D))(obs)] of 3.1+/-0.2, which is consistent with the existence of
      a cytochrome P450-like intermediate in the reaction cycle of APOs. Our results
      indicate that fungal peroxygenases may be useful biocatalytic tools to prepare
      pharmacologically relevant drug metabolites.

PMID- 21723856
TI  - Gestational- and age-specific CRP reference intervals in the newborn.

PMID- 21723854
TI  - Nicotinic control of adult-born neuron fate.
AB  - The hippocampus is one of only two regions in the adult brain where neurons are
      generated in significant numbers throughout the lifetime of the animal. Numerous
      studies have demonstrated that these adult-born neurons are essential for optimal
      cognitive function with unimpaired memory formation and retrieval. The extent to
      which adult-born neurons survive through an early "critical period" and become
      integrated into functional networks has been shown to depend on the richness of
      stimulation they receive during these formative stages. The dentate gyrus in the
      hippocampus - home of the adult-born neurons - receives extensive cholinergic
      innervation, and newly generated neurons in the adult hippocampus express
      substantial numbers of both major types of neuronal nicotinic acetylcholine
      receptors. Early studies indicated that nicotinic signaling may be important for
      the development of adult-born neurons: repeated exposure to nicotine impaired
      their long-term survival. Recent studies with mutant mice lacking either one of
      the two major nicotinic receptor subtypes demonstrate that receptor loss results
      in fewer adult-born neurons surviving the critical period and becoming integrated
      into neural networks. The key nicotinic receptor mediating the largest effects is
      one that has a high relative permeability to calcium. In view of this feature, it
      may not be surprising that excessive exposure to nicotine can have detrimental
      effects on survival and maturation of adult-born neurons in the dentate; these
      same receptors appear to be key. The results pose serious challenges for
      therapeutic strategies targeting an individual class of nicotinic receptors for
      global treatment in the recipient.

PMID- 21723857
TI  - Limitations of extensive TPMT genotyping in the management of azathioprine
      induced myelosuppression in IBD patients.
AB  - BACKGROUND AND AIMS: TPMT deficiency is associated with azathioprine (AZA)
      induced myelosuppression (MS). However, in one previous study, only about 1/4 of
      MS episodes in Crohn's Disease patients under AZA can be attributed to TPMT
      deficiency. Recently, new TPMT mutations have been described and our aim is to
      investigate their clinical relevance before and after a first MS episode on
      thiopurine therapy. METHODS: Clinical data from 61 IBD patients having developed
      MS during AZA therapy were collected. Sequencing analysis was carried out on TPMT
      cDNA for the presence of all currently known mutations. RESULTS: Only TPMT *2,
      *3A and *3C mutations were found in this cohort. TPMT mutations were observed in
      15 out of 61 patients (25%). Four out of 15 were homozygous for a TPMT mutation
      (low methylator, LM genotype) and 11 were heterozygous (intermediate methylator,
      IM genotype). Median delays of MS onset were 2, 2.75 and 6months in the LM, IM
      and HM (high methylator, wild type TPMT) groups, respectively. After the first MS
      episode, 36 patients resumed thiopurine treatment of which 13 experienced a
      second MS episode. This second episode was also rarely associated with TPMT
      mutations. CONCLUSIONS: One quarter of MS episodes during AZA were associated
      with TPMT deficient genotype. After a first leucopenia episode, thiopurine
      therapy may be resumed in a majority of patients independently of their TPMT
      genotype.

PMID- 21723858
TI  - Soluble lectin-like oxidized low-density lipoprotein receptor-1 levels in
      synovial fluid are correlated with disease severity of knee osteoarthritis.
AB  - OBJECTIVES: This study was aimed to measure soluble lectin-like oxidized low
      density lipoprotein receptor-1 (sLOX-1) levels in serum and synovial fluid (SF)
      of knee osteoarthritis (OA) patients and to investigate the correlation between
      sLOX-1 levels and the disease severity. DESIGN AND METHODS: Two hundred and
      sixteen OA patients and 83 healthy controls were enrolled in this study. All OA
      patients were scored for Kellgren-Lawrence (KL) grade (0-4). The sLOX-1 levels
      were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In OA
      patients, the mean sLOX-1 levels in SF were markedly lower than those in paired
      serum samples (P<0.01). The SF sLOX-1 levels increased with higher KL grade
      (P<0.01) and were significantly correlated with disease severity (r = 0.324,
      P<0.01). SF sLOX-1 level was the independent factor for predicting the disease
      severity of OA (beta: 0.281, 95%CI: 0.145-0.396). CONCLUSIONS: SF sLOX-1 levels
      were independently and positively associated with disease severity in knee OA.

PMID- 21723859
TI  - magu is required for germline stem cell self-renewal through BMP signaling in the
      Drosophila testis.
AB  - Understanding how stem cells are maintained in their microenvironment (the niche)
      is vital for their application in regenerative medicine. Studies of Drosophila
      male germline stem cells (GSCs) have served as a paradigm in niche-stem cell
      biology. It is known that the BMP and JAK-STAT pathways are necessary for the
      maintenance of GSCs in the testis (Kawase et al., 2004; Kiger et al., 2001;
      Schulz et al., 2004; Shivdasani and Ingham, 2003; Tulina and Matunis, 2001).
      However, our recent work strongly suggests that BMP signaling is the primary
      pathway leading to GSC self-renewal (Leatherman and DiNardo, 2010). Here we show
      that magu controls GSC maintenance by modulating the BMP pathway. We found that
      magu was specifically expressed from hub cells, and accumulated at the testis
      tip. Testes from magu mutants exhibited a reduced number of GSCs, yet maintained
      a normal population of somatic stem cells and hub cells. Additionally, BMP
      pathway activity was reduced, whereas JAK-STAT activation was retained in mutant
      testes. Finally, GSC loss caused by the magu mutation could be suppressed by
      overactivating the BMP pathway in the germline.

PMID- 21723860
TI  - Offerings from an urchin.
AB  - There is a natural curiosity about how organisms give rise to offspring like
      themselves through a series of reproducible developmental events and how, once
      mature, these offspring mate and continue the process giving rise the next
      generation. In the mid-1800s investigators started using gametes and embryos to
      explore this process. Although the observations and experimental approaches
      changed over time, embryologists and developmental biologists after them, sought
      understanding of development and inheritance through the study of gametes and
      embryos. It is argued here that in their quests to understand these processes
      embryologists made major conceptual advances that were seminal to the origins of
      genetics and to the origins of molecular biology. Furthermore these advances
      derived from the distinct perspective of those investigators with focused
      interest on the development of the organism. In this essay fundamental
      discoveries that originated with the sea urchin embryo as an experimental system
      are used to illustrate this position. The sea urchin has a long and uninterrupted
      history as a model organism that helped prepare the ground for the emergence of
      genetics and contributed important aspects to understanding of the central dogma
      of molecular biology. As molecular biology came of age new concepts and
      technology of the discipline were transformative for developmental biology and to
      this day the reciprocal inductive interactions between molecular biology and
      developmental biology continue to revitalize each other.

PMID- 21723861
TI  - Dexamethasone induces transcriptional activation of Bcl-xL gene and inhibits
      cardiac injury by myocardial ischemia.
AB  - Psychological or physical stress causes an elevation of glucocorticoids in the
      circulating system. Glucocorticoids regulate a variety of physiological
      functions, from energy metabolism and biochemical homeostasis to immune response.
      Synthetic steroids are among the most prescribed drugs for immune suppression and
      chemotherapy. While glucocorticoids are best known for inducing apoptosis in a
      number of cell types, we have found that corticosteroids at stress relevant
      levels protect cardiomyocytes from apoptosis. Current study addresses whether
      glucocorticoids inhibit cardiac injury in vivo. Adult male C57BL6 mice were
      administered with dexamethasone (20mg/kg, i.p.) or vehicle control 20 h prior to
      left anterior descending coronary artery occlusion surgery. Myocardial infarction
      was measured by triphenyl tetrazoliumchloride staining in tissue slices and by
      levels of cardiac Troponin (cTn I) in the blood. Treatment of dexamethasone
      markedly reduced infarct size (19.6 +/- 4.3%, vs. 29.2 +/- 4.9%, p<0.01) and cTn
      I level in the blood (3.83 +/- 0.66 ng/ml vs. 5.62 +/- 0.37 ng/ml, p<0.01). In
      studying the mechanism of such protection, we found that dexamethasone induces
      the expression of Bcl-xL gene in the myocardium. With cardiomyocytes in culture,
      glucocorticoids increased transcription of Bcl-xL gene as evidenced by Bcl-xL
      mRNA increase and promoter activation. The glucocorticoid receptor antagonist
      mifepristone prevented dexamethasone from inducing cardiac protection or Bcl-xL
      expression. Our data suggest that activation of glucocorticoid receptor can
      prevent cardiac injury through transcriptional activation of Bcl-xL gene.

PMID- 21723862
TI  - Investigation of neurogenic excitatory and inhibitory motor responses and their
      control by 5-HT(4) receptors in circular smooth muscle of pig descending colon.
AB  - The aim of this study was to investigate whether the pig colon descendens might
      be a good model for the responses mediated via the different locations of human
      colonic 5-HT(4) receptors. The intrinsic excitatory and inhibitory motor
      neurotransmission in pig colon descendens was therefore first characterized. In
      circular smooth muscle strips, electrical field stimulation (EFS) at basal tone
      induced only in the combined presence of the NO synthase inhibitor N(omega)-nitro
      L-arginine methyl ester hydrochloride (L-NAME) and the SK channel blocker apamin
      voltage-dependent on-contractions. These on-contractions were largely reduced by
      the neuronal conductance blocker tetrodotoxin (TTX) and by the muscarinic
      receptor antagonist atropine, illustrating activation of cholinergic neurons. The
      5-HT(4) receptor agonist prucalopride facilitated submaximal EFS-evoked
      cholinergic contractions and this effect was prevented by the 5-HT(4) receptor
      antagonist GR113808, supporting the presence of facilitating 5-HT(4) receptors on
      the cholinergic nerve endings innervating circular muscle in pig colon
      descendens. Relaxations were induced by EFS in strips pre-contracted with
      substance P in the presence of atropine. The responses at lower stimulation
      voltages were abolished by TTX. L-NAME or apamin alone did not influence or only
      moderately reduced the relaxations, but L-NAME plus apamin abolished the
      relaxations at lower stimulation voltages, suggesting that NO and ATP act as
      inhibitory neurotransmitters in a redundant way. Prucalopride did not influence
      the EFS-induced relaxations at lower stimulation voltage, nor did it per se relax
      contracted circular muscle strips. No evidence for relaxing 5-HT(4) receptors,
      either on inhibitory neurons or on the muscle cells was thus obtained in pig
      colon descendens circular muscle.

PMID- 21723863
TI  - Neonatal systemic delivery of scAAV9 in rodents and large animals results in gene
      transfer to RPE cells in the retina.
AB  - Systemic delivery of recombinant adeno-associated virus (rAAV) vectors has
      recently been shown to cross the blood brain barrier in rodents and large animals
      and to efficiently target cells of the central nervous system. Such approach
      could be particularly interesting to treat lysosomal storage diseases or
      neurodegenerative disorders characterized by multiple organs injuries especially
      neuronal and retinal dysfunctions. However, the ability of rAAV vector to cross
      the blood retina barrier and to transduce retinal cells after systemic injection
      has not been precisely determined. In this study, gene transfer was investigated
      in the retina of neonatal and adult rats after intravenous injection of self
      complementary (sc) rAAV serotype 1, 5, 6, 8, and 9 carrying a CMV-driven green
      fluorescent protein (GFP), by fluorescence fundus photography and histological
      examination. Neonatal rats injected with scAAV2/9 vector displayed the strongest
      GFP expression in the retina, within the retinal pigment epithelium (RPE) cells.
      Retinal tropism of scAAV2/9 vector was further assessed after systemic delivery
      in large animal models, i.e., dogs and cats. Interestingly, efficient gene
      transfer was observed in the RPE cells of these two large animal models following
      neonatal intravenous injection of the vector. The ability of scAAV2/9 to
      transduce simultaneously neurons in the central nervous system, and RPE cells in
      the retina, after neonatal systemic delivery, makes this approach potentially
      interesting for the treatment of infantile neurodegenerative diseases
      characterized by both neuronal and retinal damages.

PMID- 21723864
TI  - The immediate early genes Fos and Egr1 become STAT1 transcriptional targets in
      the absence of STAT3.
AB  - Signal transducer and activators of transcription (STAT)1 and STAT3 cross
      regulate their activity downstream of gp130 cytokines, and eliminating STAT3
      leads to IFN-gamma-like responses to IL-6 correlating with prolonged STAT1
      phosphorylation. Here we demonstrate that the increased gp130-mediated induction
      of the IFN-gamma-responsive interferon regulatory factor 1 gene observed in
      STAT3(-/-) cells correlates with prolonged STAT1 binding to its promoter.
      Intriguingly, gp130-mediated induction of the immediate early genes FBJ
      osteosarcoma oncogene and early growth response 1 is also prolonged in STAT3(-/-)
      cells, with STAT1 binding to their promoters. Thus the abrogation of STAT3
      expression, perturbing the signaling balance, directs the STAT1 oncosuppressor to
      transcribe new target genes, known to drive mitogen responses and tumor
      transformation.

PMID- 21723865
TI  - Sost down-regulation by mechanical strain in human osteoblastic cells involves
      PGE2 signaling via EP4.
AB  - Sclerostin is a potent inhibitor of bone formation which is down-regulated by
      mechanical loading. To investigate the mechanisms involved we subjected Saos2
      human osteoblastic cells to short periods of dynamic strain and used quantitative
      reverse transcriptase polymerase chain reaction to compare their responses to
      unstrained controls. Strain-induced Sost down-regulation was recapitulated by
      cyclo-oxygenase-2-mediated PGE2, acting through the EP4 receptor, whereas strain
      related up-regulation of osteocalcin was mediated by the EP2 receptor. Strain
      related Sost regulation required extracellular signal-regulated kinase signaling,
      whereas osteocalcin required protein kinase C. These findings indicate early
      divergence in the signaling pathways stimulated by strain and establish PGE2/EP4
      as the pathway used by strain to regulate Sost expression.

PMID- 21723866
TI  - Engineering of a multicellular organotypic model of the human intestinal mucosa.

PMID- 21723867
TI  - Anxiogenic and antinociceptive effects induced by corticotropin-releasing factor
      (CRF) injections into the periaqueductal gray are modulated by CRF1 receptor in
      mice.
AB  - Chemical or electrical stimulation of the dorsal portion of the midbrain
      periaqueductal gray (dPAG) produces anxiogenic and antinociceptive effects. In
      rats, chemical stimulation of dPAG by local infusion of the neuropeptide
      corticotropin-releasing factor (CRF) provokes anxiogenic effects in the elevated
      plus-maze test (EPM). CRF also produces antinociception when injected
      intracerebroventricularly in rats, however it remains unclear whether this
      response is also observed following CRF injection into the dPAG in mice. Yet,
      given that there are CRF1 and CRF2 receptor subtypes within the PAG, it is
      important to show in which receptor subtypes CRF exert its anxiogenic and
      antinociceptive effects in the dPAG. Here, we investigated the role of these
      receptors in the anxiogenic (assessed in the EPM) and antinociceptive (assessed
      by the Formalin test: 2.5% formalin injection into the right hind paw) effects
      following intra-dPAG infusion of CRF in mice. The results show that intra-dPAG
      injections of CRF (75 pmol/0.1MUl and 150 pmol/0.2 MUl) produced dose-dependent
      anxiogenic and antinociceptive effects. In addition, local infusion of NBI 27914
      (5-chloro-4-(N-(cyclopropyl)methyl-N-propylamino)-2-methyl-6-(2,4,6
      trichlorophenyl)-aminopyridine; 2 nmol/0.2 MUl), a CRF1 receptor antagonist,
      completely blocked both the anxiogenic and antinociceptive effects induced by
      local infusion of CRF, while that of antisauvagine 30 (ASV30; 1nmol/0.2MUl), a
      CRF2 receptor antagonist, did not alter the CRF effects. Present results are
      suggestive that CRF1 (but not CRF2) receptors play a crucial role in the
      anxiogenic and antinociceptive effects induced by CRF in the dPAG in mice.

PMID- 21723869
TI  - Effective in vitro expansion of CD40-activated human B lymphocytes in a defined
      bovine protein-free medium.
AB  - CD40-CD154 interaction is used to culture human B lymphocytes, which are now
      viewed as effectors to potentially promote T lymphocyte response against
      malignant cells in cell-based therapy. Currently, the media used, based on bovine
      serum, are raising concerns for patient safety in such therapy. In this study, we
      have investigated whether human B lymphocytes could be cultured in the absence of
      bovine serum. Blood CD19(+) B lymphocytes were activated using interaction
      through CD40 in medium containing defined animals or human proteins and lipids,
      and were monitored during short-term periods (<=15 days). Conventional stem-cell
      medium and a medium containing human albumin instead of bovine albumin were
      tested. We observed that the response of B lymphocytes appeared influenced by lot
      to-lot variability in low density lipoproteins (LDL). Nevertheless, B lymphocyte
      proliferation and secretion in serum-free and bovine protein-free media were
      quite similar to that of cells cultured in medium containing FBS. Our results
      show that CD40-activated B lymphocytes can be cultured for up to 15 days in a
      serum-free medium containing human albumin, LDL, alpha-tocopherol and chemically
      defined lipids.

PMID- 21723870
TI  - Screening and characterization of new monoclonal anti-benzo[a]pyrene antibodies
      using automated flow-through microarray technology.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants,
      which can cause cancer in humans. The maximum tolerable limit of benzo[a]pyrene
      (B[a]P) in drinking water was set to 10 ng/L by the European Commission (Council
      Directive 98/83/EC), because of its highly carcinogenic and mutagenic effect on
      humans. In the present investigation, mice were immunized with B[a]P-bovine serum
      albumin conjugates and 110 generated hybridoma cell lines screened by different
      techniques to identify clones that produce anti-B[a]P antibodies. Subsequently, a
      new automated flow-through biochip noncompetitive direct chemiluminescence
      immunoassay (CLEIA) was compared with conventional indirect and direct enzyme
      linked immunosorbent assays (ELISAs). It was demonstrated that the microchip
      based screening method compared to ELISA was fast and very sensitive with use of
      only nanoliter volumes of supernatant. Forty clones could be evaluated in less
      than 5 min. Six high affinity monoclonal antibodies with different cross
      reactivities (CR) for individual PAHs were identified by the chip-based assay and
      indirect microtiter plate ELISA. In comparison, the direct ELISA in the
      microtiter plate failed to identify three of these clones. The four antibodies
      with the highest affinity had half maximum inhibitory concentrations (IC(50)
      values) between 0.31 and 0.92 MUg/L for B[a]P. Affinity constants of these four
      antibodies were determined by surface plasmon resonance using a water soluble
      B[a]P-peptide. The observed CR pattern of the four monoclonal antibodies for 16
      tested PAHs was quite different. Only one specific antibody for B[a]P was
      observed, while others were more suitable for class-specific PAH determination.

PMID- 21723871
TI  - Carboxy-terminal extension effects on crystal formation and insecticidal
      properties of Cry15Aa.
AB  - Cry15Aa protein, produced by Bacillus thuringiensis serovar thompsoni HD542, in a
      crystal together with a 40 kDa accompanying protein, is one of a small group of
      non-typical, less well-studied members of the Cry family of insecticidal
      proteins, and may provide an alternative for the more commonly used Cry proteins
      in insect pest management. In this study we examined the role of the C-terminal
      part of Cry15Aa and of the 40 kDa protein in crystal formation in recombinant B.
      thuringiensis. The contribution of the 40 kDa protein and of the Cry15Aa carboxy
      terminal sequence for crystal formation, crystal solubilization, and insecticidal
      properties was assessed. No significant differences in toxicity against Cydia
      pomonella, before or after in vitro solubilization of crystal-spore preparations,
      were found. Although the 40 kDa protein significantly contributes to in vitro
      solubility and in vivo crystal formation of Cry15Aa, no direct evidence for
      involvement of the 40 kDa protein in toxicity of Cry15Aa was found.

PMID- 21723868
TI  - Mining the Giardia genome and proteome for conserved and unique basal body
      proteins.
AB  - Giardia lamblia is a flagellated protozoan parasite and a major cause of
      diarrhoea in humans. Its microtubular cytoskeleton mediates trophozoite motility,
      attachment and cytokinesis, and is characterised by an attachment disk and eight
      flagella that are each nucleated in a basal body. To date, only 10 giardial basal
      body proteins have been identified, including universal signalling proteins that
      are important for regulating mitosis or differentiation. In this study, we have
      exploited bioinformatics and proteomic approaches to identify new Giardia basal
      body proteins and confocal microscopy to confirm their localisation in interphase
      trophozoites. This approach identified 75 homologs of conserved basal body
      proteins in the genome including 65 not previously known to be associated with
      Giardia basal bodies. Thirteen proteins were confirmed to co-localise with
      centrin to the Giardia basal bodies. We also demonstrate that most basal body
      proteins localise to additional cytoskeletal structures in interphase
      trophozoites. This might help to explain the roles of the four pairs of flagella
      and Giardia-specific organelles in motility and differentiation. A deeper
      understanding of the composition of the Giardia basal bodies will contribute
      insights into the complex signalling pathways that regulate its unique
      cytoskeleton and the biological divergence of these conserved organelles.

PMID- 21723872
TI  - Tuning Wnt-signaling to enhance cardiomyogenesis in human embryonic and induced
      pluripotent stem cells.

PMID- 21723873
TI  - Methods in cardiomyocyte isolation, culture, and gene transfer.
AB  - Since techniques for cardiomyocyte isolation were first developed 35 years ago,
      experiments on single myocytes have yielded great insight into their cellular and
      sub-cellular physiology. These studies have employed a broad range of techniques
      including electrophysiology, calcium imaging, cell mechanics,
      immunohistochemistry and protein biochemistry. More recently, techniques for
      cardiomyocyte culture have gained additional importance with the advent of gene
      transfer technology. While such studies require a high quality cardiomyocyte
      population, successful cell isolation and maintenance during culture remain
      challenging. In this review, we describe methods for the isolation of adult and
      neonatal ventricular myocytes from rat and mouse heart. This discussion outlines
      general principles for the beginner, but also provides detailed specific
      protocols and advice for common caveats. We additionally review methods for short
      term myocyte culture, with particular attention given to the importance of
      substrate and media selection, and describe time-dependent alterations in myocyte
      physiology that should be anticipated. Gene transfer techniques for neonatal and
      adult cardiomyocytes are also reviewed, including methods for transfection
      (liposome, electroporation) and viral-based gene delivery.

PMID- 21723874
TI  - Directed evolution of sulfotransferases and paraoxonases by ancestral libraries.
AB  - Large libraries of randomly mutated genes are applied in directed evolution
      experiments in order to obtain sufficient variability. These libraries, however,
      contain mostly inactive variants, and the very low frequency of improved variants
      can only be isolated by high-throughput screening. Small but efficient libraries
      comprise an attractive alternative. Here, we describe the application of
      ancestral libraries-libraries based on mutations predicted by phylogenetic
      analysis and ancestral inference. We designed and constructed such libraries
      using serum paraoxonases and cytosolic sulfotransferases (SULTs) as model
      enzymes. Both of these enzyme families exhibit a range of activities in drug
      metabolism and detoxification of xenobiotics. The ancestral serum paraoxonase and
      SULT libraries were screened by low-throughput means, including HPLC, using
      substrates and/or reactions with which all family members exhibit low activity.
      The libraries showed a remarkably high frequency of highly polymorphic and
      functionally diverse variants. Screening of as few as 300 variants enabled the
      isolation of mutants with up to 50-fold higher activity than the starting point
      enzyme. Structural and kinetic characterizations of an evolved SULT variant show
      how few ancestral mutations reshaped the active site and modulated the enzyme's
      specificity. Ancestral libraries therefore comprise a means of focusing diversity
      to positions and mutations that readily trigger changes in substrate and/or
      reaction specificity, thereby facilitating the isolation of new enzyme variants
      for a variety of different substrates and reactions by medium-throughput or even
      low-throughput screens.

PMID- 21723875
TI  - Enzyme inhibition by allosteric capture of an inactive conformation.
AB  - All members of the human herpesvirus protease (HHV Pr) family are active as
      weakly associating dimers but inactive as monomers. A small-molecule allosteric
      inhibitor of Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr) traps the
      enzyme in an inactive monomeric state where the C-terminal helices are unfolded
      and the hydrophobic dimer interface is exposed. NMR titration studies demonstrate
      that the inhibitor binds to KSHV Pr monomers with low micromolar affinity. A 2.0
      A-resolution X-ray crystal structure of a C-terminal truncated KSHV Pr-inhibitor
      complex locates the binding pocket at the dimer interface and displays
      significant conformational perturbations at the active site, 15 A from the
      allosteric site. NMR and CD data suggest that the small molecule inhibits human
      cytomegalovirus protease via a similar mechanism. As all HHV Prs are functionally
      and structurally homologous, the inhibitor represents a class of compounds that
      may be developed into broad-spectrum therapeutics that allosterically regulate
      enzymatic activity by disrupting protein-protein interactions.

PMID- 21723876
TI  - Flow-induced pruning of branched systems and brittle reconfiguration.
AB  - Whereas most plants are flexible structures that undergo large deformations under
      flow, another process can occur when the plant is broken by heavy fluid-loading.
      We investigate here the mechanism of such possible breakage, focusing on the flow
      induced pruning that can be observed in plants or aquatic vegetation when parts
      of the structure break under flow. By computation on an actual tree geometry, a
      20-yr-old walnut tree (Juglans Regia L.) and comparison with simple models, we
      analyze the influence of geometrical and physical parameters on the occurrence of
      branch breakage and on the successive breaking events occurring in a tree-like
      structure when the flow velocity is increased. We show that both the branching
      pattern and the slenderness exponent, defining the branch taper, play a major
      role in the breakage scenario. We identify a criterion for branch breakage to
      occur before breakage of the trunk. In that case, we show that the successive
      breakage of peripheral branches allows the plant to sustain higher flow forces.
      This mechanism is, therefore, similar to elastic reconfiguration, and can be seen
      as a second strategy to overcome critical events, possibly a widespread solution
      in plants and benthic organisms.

PMID- 21723877
TI  - Vascular dysfunction and impaired insulin signaling in high-fat diet fed
      ovariectomized mice.
AB  - The metabolic syndrome, characterized by conditions such as obesity and insulin
      resistance, is more prevalent in postmenopausal women than in premenopausal
      women, and increases the risk of cardiovascular disease and type 2 diabetes. The
      main objective of the present study was to investigate the combined effects of
      ovariectomy (OVX) and high-fat diet (HFD) on metabolic parameters, vascular
      function and glucose homeostasis in mice. After OVX or sham operation (Sham),
      mice were fed with either a normal diet (ND) or a HFD. Mice were divided into
      ND+Sham, ND+OVX, HFD+Sham, and HFD+OVX groups. After 4weeks, HFD+OVX mice
      developed marked increases in body weight and plasma insulin levels, but not
      blood glucose levels. The area under the glucose tolerance curve (Delta
      AUC(glucose)) following an oral glucose tolerance test and the homeostasis model
      assessment of insulin resistance (HOMA-IR) revealed that HFD+OVX mice had higher
      values than any other group. Concomitantly with these metabolic disturbances,
      decreased tail skin blood flow and augmented tail skin flushing, a marker of hot
      flashes, were observed in HFD+OVX mice. These vascular modulations likely result
      from vasomotor dysfunction. Furthermore, we investigated whether OVX and HFD
      affect the insulin signaling pathway in mice. Insulin-induced Akt phosphorylation
      in the livers of HFD+OVX mice was significantly downregulated compared with
      ND+Sham and HFD+Sham mice. Thus, the HFD+OVX mice used in the present study
      constitute an experimental animal model of postmenopausal metabolic syndrome.
      Herein, we provide experimental evidence that vascular dysfunction and impaired
      insulin signaling may contribute to the pathogenesis of postmenopausal metabolic
      syndrome.

PMID- 21723878
TI  - Coagulant effects of black snake (Pseudechis spp.) venoms and in vitro efficacy
      of commercial antivenom.
AB  - The coagulant effects of Australasian black snakes (Pseudechis spp.) are poorly
      understood and differ to the procoagulant venoms of most dangerous snakes in
      Australia. This study aimed to investigate in vitro coagulant effects of
      Pseudechis venoms and the efficacy of commercial black snake antivenom (BlSAV),
      tiger snake antivenom (TSAV) and specific rabbit anti-snake IgG to neutralise
      these effects. Using a turbidimetric assay, all six Pseudechis venoms had
      anticoagulant activity, as well as phospholipase A(2) (PLA(2)) activity.
      Inhibition of PLA(2) activity removed anticoagulant effects of the venoms.
      Pseudechis porphyriacus was unique and had procoagulant activity independent of
      PLA2 activity. Both BlSAV and TSAV completely inhibited the coagulant and PLA2
      activity of all Pseudechis venoms. PLA2 activity was also inhibited completely by
      p-Bromophenacyl bromide (pBPB) and partially by specific anti-N. scutatus IgG
      antibodies. Anti-N. scutatus IgG also completely inhibited anticoagulant activity
      of Pseudechis venom. All Pseudechis venoms showed immunological cross reactivity
      with specific anti-snake IgG antibodies to P. porphyriacus, Pseudechis australis
      and Notechis scutatus. Pseudechis venoms have in vitro anticoagulant activity
      that appears to be attributable to PLA(2) activity. Both antivenoms inhibited
      anticoagulant and PLA(2) activity at concentrations below those occurring in
      patients treated with one vial of antivenom. There was cross-neutralisation of
      Pseudechis venoms and N. scutatus antibodies that might be attributable to
      immunological similarities between the venoms.

PMID- 21723879
TI  - Alcohol-preferring (P) rats are more sensitive than Wistar rats to the
      reinforcing effects of cocaine self-administered directly into the nucleus
      accumbens shell.
AB  - Wistar rats will self-administer cocaine directly into the nucleus accumbens
      shell (AcbSh), but not into the nucleus accumbens core. In human and animal
      literature, there is a genetic association between alcoholism and cocaine
      dependency. The current experiment examined whether selective breeding for high
      alcohol preference is also associated with greater sensitivity of the AcbSh to
      the reinforcing properties of cocaine. P and Wistar rats were given cocaine (0,
      100, 200, 400, or 800 pmol/100 nl) to self-infuse into the AcbSh. Rats were given
      cocaine for the first 4 sessions (acquisition), artificial CSF for sessions 5 and
      6 (extinction), and cocaine again in session 7 (reinstatement). During
      acquisition, P rats self-infused 200-800 pmol cocaine (59 infusions/session),
      whereas Wistar rats only reliably self-infused 800 pmol cocaine (38
      infusions/session). Furthermore, P rats received a greater number of cocaine
      infusions in the 200, 400 and 800 pmol cocaine groups compared to respective
      Wistar groups during acquisition. Both P and Wistar rats reduced responding on
      the active lever when aCSF was substituted for cocaine, and reinstated responding
      in session 7 when cocaine was restored. However, P rats had significantly greater
      infusions during session 7 compared to session 4 at all concentrations of cocaine
      tested, whereas Wistar rats only displayed greater infusions during session 7
      compared to session 4 at the 400 and 800 pmol cocaine concentrations. The present
      results suggest that, compared to Wistar rats, the AcbSh of P rats was more
      sensitive to the reinforcing effects of cocaine. The reinstatement data suggest
      that the AcbSh of P rats may have become sensitized to the reinforcing effects of
      cocaine. Overall, the findings from this study support a genetic association
      between high alcohol preference and greater sensitivity to the reinforcing
      effects of cocaine.

PMID- 21723881
TI  - KCNQ2/3 openers show differential selectivity and site of action across multiple
      KCNQ channels.
AB  - KCNQ2/3 voltage-gated potassium channels conduct low-threshold, slowly activating
      and non-inactivating currents to repolarize the neuronal resting membrane
      potential. The channels negatively regulate neuronal excitability and KCNQ2/3
      openers are efficacious in hyperexcited states such as epilepsy and pain. We
      developed and utilized thallium influx assays to profile novel KCNQ2/3 channel
      openers with respect to selectivity across KCNQ subtypes and on requirement for
      tryptophan 236 of KCNQ2, a critical residue for activity of the KCNQ opener
      retigabine. Using distinct chemical series of openers, a quinazolinone series
      showed relatively poor selectivity across multiple KCNQ channels and lacked
      activity at the KCNQ2(W236L) mutant channel. In contrast, several novel
      benzimidazole openers showed selectivity for KCNQ2/3 and KCNQ2 and retain
      activity at KCNQ2(W236L). Profiling of several hundred KCNQ2/3 openers across
      multiple diverse chemical series revealed that openers show differential degrees
      of selectivity across subtypes, with selectivity most difficult to achieve
      against KCNQ2. In addition, we report the significant finding that KCNQ openers
      can pharmacologically differentiate between homomeric and heteromeric channels
      containing subtypes in common. Moreover, most openers assayed were dependent on
      the W236 for activity, whereas only a small number appear to use a distinct
      mechanism. Collectively, we provide novel insights into the molecular
      pharmacology of KCNQ channels by demonstrating differential selectivity and site
      of action for KCNQ2/3 openers. The high-throughput thallium influx assays should
      prove useful for rapid characterization of KCNQ openers and in guiding efforts to
      identify selective compounds for advancement towards the clinic.

PMID- 21723880
TI  - Severe ear chondritis due to cowpox virus transmitted by a pet rat.
AB  - We describe a case of cowpox virus infection leading to severe acute inflammation
      and chondritis of the outer ear, complicated by local necrosis and facial
      cellulitis. Secondary lesions occurred on a finger and the abdomen. Apart from
      scarring, outcome was favorable after repeated surgical excision of necrotic
      tissue.

PMID- 21723882
TI  - Detection of foot-and-mouth disease virus in the breath of infected cattle using
      a hand-held device to collect aerosols.
AB  - Exhaled air of individual cattle infected experimentally with foot-and-mouth
      disease virus (FMDV) was sampled to assess the feasibility of a rapid, non
      invasive general screening approach for identifying sources of FMDV infection.
      The air sampler used was a handheld prototype device employing electrostatic
      particle capture in a microchip chamber of 10-15 MUL and was shown to effectively
      capture a high percentage of airborne microorganisms. The particles were eluted
      subsequently from the chip chamber and subjected to real-time RT-PCR. Sampling
      exhaled air for as little as 1 min allowed the detection of FMDV in cattle
      infected experimentally. Detection in exhaled air from individual cattle was
      compared to FMDV detection in serum and saliva for 3 different strains of FMDV
      (O1/Manisa/69, C/Oberbayern/FRG/1960 and SAT1/Zimbawe/1989). Detection of FMDV in
      exhaled air was possible for all strains of FMDV used for experimental infection
      but the period that detection was possible varied among the strains. Detection in
      exhaled air generally peaked on day 2-4 post infection. The perspectives of
      monitoring for FMDV in the breath of infected cattle are discussed in the context
      of real-time epidemiological contingencies.

PMID- 21723883
TI  - Evaluation of a real-time RT-PCR assay using minor groove binding probe for
      specific detection of Chinese wild-type classical swine fever virus.
AB  - A one-step real-time RT-PCR assay using a minor groove binding probe was
      developed for the specific detection of Chinese wild-type classical swine fever
      virus (CSFV). The assay detected wild-type CSFV strains representing different
      genotypes, but did not amplify viral RNA from the Hog Cholera Lipinized Virus
      (HCLV) vaccine-strain and other porcine viruses. The assay had a detection limit
      of 10 copies/reaction or 3.0 median tissue culture infective dose/reaction. In
      comparison to the sequencing nested RT-PCR assay, the sensitivity and specificity
      of the assay were 98.3% and 94.3%, respectively, when testing 515 veterinary
      samples. Wild-type CSFV RNA was detected in nasal swabs 2-4 days before detection
      in serum samples from pigs exposed to infection by contact, and 2-4 days prior to
      the onset of clinical disease. HCLV RNA remained undetectable in nasal swabs and
      serum samples from vaccinated pigs. In conclusion, the novel assay described in
      this study provides a rapid and sensitive method for differentiating between wild
      type and the HCLV-strain of CSFV. It could be used for monitoring in CSF outbreak
      areas or as a screening method for CSFV eradication strategies.

PMID- 21723884
TI  - Reassessment of motor-behavioural test analyses enables the detection of early
      disease-onset in a transgenic mouse model of amyotrophic lateral sclerosis.
AB  - As a model for amyotrophic lateral sclerosis (ALS), transgenic hSOD1(G93A) mice
      constitute the standard tool for evaluating future therapeutic strategies. Due to
      axonal retraction from neuromuscular junctions, the animals suffer from muscle
      wasting leading to weakness and paralysis of the extremities, which in early
      stages can be detected by measuring weight loss. Suspecting that underlying
      mechanisms might yield subtle neuromuscular abnormalities ahead of weight loss
      onset, we wanted to determine a behavioural test to detect disease onset time
      earlier. We compared the monitoring of weight with the "forced" examination of
      grip strength and the investigation of freely behaving animals within an open
      field. Additionally, we compared two different data analysis methods: (1) two-way
      ANOVA with Bonferroni correction (2) break point analysis calculating symptom
      onset time points for each animal. Break point analysis revealed onset times that
      significantly preceded those obtained by standard two-way ANOVA. Open field
      analysis of freely moving animals could not give an advantage over weight loss
      measurements. Grip strength assessment of hindlimbs detected disease onset 36
      days before the first evidence of weight loss, providing a maximal treatment
      window of 84 days on average before the death of male animals. We conclude that
      grip strength analysis of hindlimbs is a very sensitive and reproducible motor
      behavioural test, which can even be applied to small cohorts of animals. Combined
      with break point analysis, it represents the method of choice to detect early
      disease onset in hSOD1(G93A) mice.

PMID- 21723885
TI  - Molecular and immunological characterization of Fasciola antigens recognized by
      the MM3 monoclonal antibody.
AB  - Fascioliasis is a re-emerging parasitosis produced by liver flukes of the genus
      Fasciola. In this study we used protein fingerprinting (PMF) and MS/MS analysis
      to investigate the Fasciola secretory antigens that are recognized by mAb MM3.
      The results showed that mAb MM3 binds to several Fasciola cathepsins L1 and L2,
      but also co-purifies a Kunitz-type protein previously described in F. hepatica,
      which appears to bind to Fasciola cathepsins L. After identifying the target
      antigens for mAb MM3, we cloned and expressed a cathepsin L1 isoform in E. coli
      (gb|FR848428), which after refolding exhibited the MM3-recognized epitope and
      displayed cysteine protease activity. Using native, folded-recombinant and
      denatured-recombinant Fasciola cathepsins L as targets, we demonstrated that
      during F. hepatica infections in sheep, antibody responses to linear and
      conformational epitopes present on cathepsins L are promoted. However, the
      antibody response to linear epitopes was only detected in significant amounts in
      animals suffering from repeated infections. A different antibody response to
      linear and conformational epitopes also appears to occur in rabbits immunized
      with native or recombinant unfolded cathepsins, as sera from animals immunized
      with the latter did not react with native cathepsins and vice versa. In addition,
      the ELISA inhibitions showed that the MM3 epitope is not recognized by rabbits,
      which explains the usefulness of these species for producing capture antibodies
      for use in MM3-ELISA assays.

PMID- 21723887
TI  - Metagenomic comparison of direct and indirect soil DNA extraction approaches.
AB  - Full pyrosequencing runs of both direct-extracted (high yield, low DNA size) and
      indirect-extracted DNA (low yield, high DNA size) from the same prairie soil show
      that the sequence distribution of the majority of the metabolic functions and
      species detected were statistically similar. Although some microbial functions
      differed at the 95% confidence interval in bootstrap analyses, the overall
      functional diversity was the same.

PMID- 21723886
TI  - Evolutionary expression of glucose-dependent-insulinotropic polypeptide (GIP).
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is a mammalian incretin
      hormone released into the circulation following nutrient ingestion. We examined
      the functional evolution of GIP and its relationship with insulin to delineate
      their respective roles in promoting nutrient efficiency. Expression patterns were
      examined in the sea lamprey (Petromyzon marinus), a basal vertebrate lacking a
      distinct pancreas, and in the zebrafish, Xenopus laevis, chicken, and mouse,
      organisms possessing extraintestinal pancreata. Although sea lamprey genomic
      analysis predicted a potential GIP-like gene, transcripts were not detected, and
      insulin expression was confined to the caudal pancreatic bud. GIP was detected in
      both the intestine and pancreas of the zebrafish and X. laevis. In contrast, GIP
      and insulin expression were limited to the intestine and pancreas, respectively,
      in chicken and mouse. Phylogenetic analysis of the glucagon-like ligands
      suggested proglucagon as the common ancestor, supporting the theory that GIP
      arose as a gene duplication of proglucagon. Insulin-secreting cells in the sea
      lamprey intestine may have obviated the need for an enteroinsular axis, and
      zebrafish may represent an evolutionary transition where GIP does not yet
      function as an incretin hormone. These observations are consistent with the
      hypothesis that GIP and insulin influence survival advantage by enhancing the
      efficiency of nutrient absorption and energy storage.

PMID- 21723888
TI  - Effort reward imbalance is associated with vagal withdrawal in Danish public
      sector employees.
AB  - OBJECTIVES: The current study analyzed the relationship between psychosocial work
      environment assessed by the Effort Reward Imbalance Model (ERI-model) and heart
      rate variability (HRV) measured at baseline and again, two years later, as this
      relationship is scarcely covered by the literature. METHODS: Measurements of HRV
      during seated rest were obtained from 231 public sector employees. The
      associations between the ERI-model, and HRV were examined using a series of mixed
      effects models. The dependent variables were the logarithmically transformed
      levels of HRV-measures. Gender and year of measurement were included as factors,
      whereas age, and time of measurement were included as covariates. Subject was
      included as a random effect. RESULTS: Effort and effort reward imbalance were
      positively associated with heart rate and the ratio between low frequency (LF)
      and high frequency power (HF) and negatively associated with total power (TP) and
      HF. Reward was positively associated with TP. CONCLUSION: Adverse psychosocial
      work environment according to the ERI-model was associated with HRV, especially
      in the form of vagal withdrawal and most pronounced in women.

PMID- 21723889
TI  - Structural stability of E. coli transketolase to temperature and pH denaturation.
AB  - We have previously shown that the denaturation of TK with urea follows a non
      aggregating though irreversible denaturation pathway in which the cofactor
      binding appears to become altered but without dissociating, then followed at
      higher urea by partial denaturation of the homodimer prior to any further
      unfolding or dissociation of the two monomers. Urea is not typically present
      during biocatalysis, whereas access to TK enzymes that retain activity at
      increased temperature and extreme pH would be useful for operation under
      conditions that increase substrate and product stability or solubility. To
      provide further insight into the underlying causes of its deactivation in process
      conditions, we have characterised the effects of temperature and pH on the
      structure, stability, aggregation and activity of Escherichia coli transketolase.
      The activity of TK was initially found to progressively improve after pre
      incubation at increasing temperatures. Loss of activity at higher temperature and
      low pH resulted primarily from protein denaturation and subsequent irreversible
      aggregation. By contrast, high pH resulted in the formation of a native-like
      state that was only partially inactive. The apo-TK enzyme structure content also
      increased at pH 9 to converge on that of the holo-TK. While cofactor dissociation
      was previously proposed for high pH deactivation, the observed structural changes
      in apo-TK but not holo-TK indicate a more complex mechanism.

PMID- 21723890
TI  - Development of microRNA-145 for therapeutic application in breast cancer.
AB  - MicroRNAs, small non-coding RNAs, are key regulators of tumorigenesis and cancer
      metastasis through inhibition of gene expression. Therefore, there is increasing
      interest in developing anti-cancer therapies using microRNAs. In this study, we
      determined the therapeutic potency of microRNA-145(miR-145) against breast
      cancer. We found a reverse-correlation between the expression of miR-145 and its
      target genes, such as fascin-1, c-myc, SMAD2/3 and IGF-1R in breast cancer cell
      lines and breast cancer patient tissues. Transfected miR-145 mimicking double
      stranded oligonucleotides was directly reduced cell proliferation and motility
      via interaction with 3'UTR of target gene and also indirectly regulates Wnt
      signaling. An inhibitor of miR-145 nullified this decreasing effect of miR-145 on
      cell proliferation and motility. We prepared an adenoviral constructed miR-145(Ad
      miR-145) and subjected it to breast cancer cells in vitro and orthotopic breast
      cancer mice in vivo. Ad-miR-145 suppressed cell growth and motility in both the
      in vitro and in vivo systems. Furthermore, a treatment combining Ad-miR-145 with
      5-FU significantly showed anti-tumor effects, compared to treating alone. In
      conclusion, this study demonstrated that miR-145 suppresses tumor growth by
      inhibition of multiple tumor survival effectors, and more we suppose that miR-145
      is potentially useful in the therapy of breast cancers.

PMID- 21723891
TI  - Inorganic nanoparticles for cancer imaging and therapy.
AB  - Inorganic nanoparticles have received increased attention in the recent past as
      potential diagnostic and therapeutic systems in the field of oncology. Inorganic
      nanoparticles have demonstrated successes in imaging and treatment of tumors both
      ex vivo and in vivo, with some promise towards clinical trials. This review
      primarily discusses progress in applications of inorganic nanoparticles for
      cancer imaging and treatment, with an emphasis on in vivo studies. Advances in
      the use of semiconductor fluorescent quantum dots, carbon nanotubes, gold
      nanoparticles (spheres, shells, rods, cages), iron oxide magnetic nanoparticles
      and ceramic nanoparticles in tumor targeting, imaging, photothermal therapy and
      drug delivery applications are discussed. Limitations and toxicity issues
      associated with inorganic nanoparticles in living organisms are also discussed.

PMID- 21723892
TI  - Prolonged circulation and in vivo efficacy of recombinant human granulocyte
      colony-stimulating factor encapsulated in polymeric micelles.
AB  - To improve the pharmacokinetics of granulocyte colony-stimulating factor (G-CSF)
      and decrease dosing frequency, polyethylene glycol polyglutamate block copolymers
      were used as delivery carriers. The block copolymers are partially substituted
      with hydrophobic octyl or benzyl groups to form a micellar structure in aqueous
      media and encapsulate the protein. G-CSF is encapsulated in the polymeric
      micelles with a diameter of 60-70nm. The present study was designed to evaluate
      the plasma pharmacokinetics, G-CSF release and in vivo efficacy of G-CSF
      encapsulating micelles. Pharmacokinetic studies in rats showed highly enhanced
      plasma retention of the micelles compared with native G-CSF. The AUC (area under
      the curve) of the octyl-based polymer formulation showed a 5-fold increase,
      compared with native G-CSF. Size-exclusion chromatography of the blood from rats
      injected with the micelles demonstrated the release of G-CSF from the micelles in
      the blood circulation. The pharmacokinetic behavior supports the in vivo studies
      showing that the micelles display a comparable efficacy to PEGylated G-CSF.
      Simultaneous pharmacokinetic analysis of released and encapsulated G-CSF plasma
      levels showed that the G-CSF release occurs with the first-order kinetics and the
      half-life is 4.8h. In conclusion, G-CSF is endowed by the polymeric micelles with
      prolonged half-life and increased efficacy without any chemical modification.

PMID- 21723893
TI  - Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic
      ligand conjugates.
AB  - Biodegradable polymeric nanoparticles are widely recognized as efficacious drug
      delivery vehicles, yet the rational engineering of nanoparticle surfaces in order
      to improve biodistribution, reduce clearance, and/or improve targeting remains a
      significant challenge. We have previously demonstrated that an amphiphilic
      conjugate of avidin and palmitic acid can be used to modify poly(lactic-co
      glycolic acid) (PLGA) particle surfaces to display functional avidin groups,
      allowing for the facile attachment of biotinylated ligands for targeting or
      steric stabilization. Here, we hypothesized that the incorporation, density, and
      stability of surface-presented avidin could be modulated through varying the
      lipophilicity of its fatty acid conjugate partner. We tested this hypothesis by
      generating a set of novel conjugates incorporating avidin and common fatty acids.
      We found that conjugation to linoleic acid resulted in a ~60% increase in the
      incorporation of avidin on the nanoparticle surface compared to avidin-palmitic
      acid, which exhibited the highest avidin incorporation in previous studies.
      Further, the linoleic acid-avidin conjugate yielded nanoparticles with enhanced
      ability to bind biotinylated ligands compared to the previous method;
      nanoparticles modified with avidin-linoleic acid bound ~170% more biotin-HRP than
      those made with avidin-palmitic acid and ~1300% more than particles made without
      conjugated avidin. Most critically, increased ligand density on anti-CD4-targeted
      nanoparticles formulated with the linoleic acid-avidin conjugate resulted in a 5%
      increase in binding of CD4(+) T cells. Thus we conclude that the novel avidin
      linoleic acid conjugate facilitates enhanced ligand density on PLGA
      nanoparticles, resulting in functional enhancement of cellular targeting.

PMID- 21723894
TI  - Consumers' attitudes toward consumption of cloned beef. The impact of exposure to
      technological information about animal cloning.
AB  - Novel food technologies, such as cloning, have been introduced into the meat
      production sector; however, their use is not widely supported by many consumers.
      This study was designed to assess whether Japanese consumers' attitudes toward
      consumption of cloned beef (specifically, beef derived from bovine embryo and
      somatic cell-cloned cattle) would change after they were provided with
      technological information on animal cloning through a web-based survey. The
      results revealed that most respondents did not discriminate between their
      attitudes toward the consumption of the two types of cloned beef, and that most
      respondents did not change their attitudes toward cloned beef after receiving the
      technological information. The respondents' individual characteristics, including
      their knowledge about the food safety of cloned beef and their basic knowledge
      about animal cloning, influenced the likelihood of a change in their attitudes
      after they received the information. In conclusion, some consumers might become
      less uncomfortable about the consumption of cloned beef by the straightforward
      provision of technological information about animal cloning; however, most
      consumers are likely to maintain their attitudes.

PMID- 21723895
TI  - MicroRNA function and neurotrophin BDNF.
AB  - MicroRNAs (miRs), endogenous small RNAs, regulate gene expression through
      repression of translational activity after binding to target mRNAs. miRs are
      involved in various cellular processes including differentiation, metabolism, and
      apoptosis. Furthermore, possible involvement of miRs in neuronal function have
      been proposed. For example, miR-132 is closely related to neuronal outgrowth
      while miR-134 plays a role in postsynaptic regulation, suggesting that brain
      specific miRs are critical for synaptic plasticity. On the other hand, numerous
      studies indicate that BDNF (brain-derived neurotrophic factor), one of the
      neurotrophins, is essential for a variety of neuronal aspects such as cell
      differentiation, survival, and synaptic plasticity in the central nervous system
      (CNS). Interestingly, recent studies, including ours, suggest that BDNF exerts
      its beneficial effects on CNS neurons via up-regulation of miR-132. Here, we
      present a broad overview of the current knowledge concerning the association
      between neurotrophins and various miRs.

PMID- 21723896
TI  - Amyloid-beta induced toxicity involves ganglioside expression and is sensitive to
      GM1 neuroprotective action.
AB  - The effect of Abeta25-35 peptide, in its fibrillar and non-fibrillar forms, on
      ganglioside expression in organotypic hippocampal slice cultures was
      investigated. Gangliosides were endogenously labeled with D-[1-C(14)] galactose
      and results showed that Abeta25-35 affected ganglioside expression, depending on
      the peptide aggregation state, that is, fibrillar Abeta25-35 caused an increase
      in GM3 labeling and a reduction in GD1b labeling, whereas the non-fibrillar form
      was able to enhance GM1 expression. Interestingly, GM1 exhibited a
      neuroprotective effect in this organotypic model, since pre-treatment of the
      hippocampal slices with GM1 10 MUM was able to prevent the toxicity triggered by
      the fibrillar Abeta25-35, when measured by propidium iodide uptake protocol. With
      the purpose of further investigating a possible mechanism of action, we analyzed
      the effect of GM1 treatment (1, 6, 12 and 24h) upon the Abeta-induced alterations
      on GSK3beta dephosphorylation/activation state. Results demonstrated an important
      effect after 24-h incubation, with GM1 preventing the Abeta-induced
      dephosphorylation (activation) of GSK3beta, a signaling pathway involved in
      apoptosis triggering and neuronal death in models of Alzheimer's disease. Taken
      together, present results provide a new and important support for ganglioside
      participation in development of Alzheimer's disease experimental models and
      suggest a protective role for GM1 in Abeta-induced toxicity. This may be useful
      for designing new therapeutic strategies for Alzheimer's treatment.

PMID- 21723897
TI  - Abeta(42) induced MRI changes in aged rabbit brain resembles AD brain.
AB  - Alzheimer's disease is the most common form of dementia and is structurally
      characterized by brain atrophy and loss of brain volume. Abeta is one of the
      widely accepted causative factors of AD. Abeta deposition is positively
      correlated with brain atrophy in AD. In the present study, structural brain
      imaging techniques such as Magnetic Resonance Imaging (MRI) were used to measure
      neuroanatomical alterations in Alzheimer's disease brain. MRI is a non-invasive
      method to study brain structure. The objective of the present study was to
      elucidate the role of Abeta on brain structure in the aged rabbit brain. Among 20
      aged rabbits, one batch (n=10) rabbits was injected chronically with Abeta(1-42)
      and another batch (n=10) with saline. The MRI was conducted before Abeta(1
      42)/saline injection and after 45 days of Abeta(1-42)/saline injection. All the
      aged rabbits underwent MRI analysis and were euthanized after 45 days. The MRI
      results showed a significant reduction in thickness of frontal lobe, hippocampus,
      midbrain, temporal lobe and increases in the lateral ventricle volume. We also
      conducted an MRI study on AD (n=10) and normal (n=10) cases and analyzed for the
      thicknesses of frontal lobe, hippocampus, midbrain, temporal lobe and lateral
      ventricle lobe. We found significant reductions in thickness of the frontal lobe
      and the hippocampus. However, no significant reduction in the thickness of
      midbrain, temporal lobe or increase in the lateral ventricle volume was observed
      compared to normal. Correlations in brain atrophy changes between rabbit brain
      and human AD brain were found for frontal lobe and hippocampal regions. In
      contrast, other regions such as midbrain, temporal lobe, and lateral ventricles
      were not correlated with rabbit brain atrophy changes in the corresponding
      regions. The relevance of these changes in AD is discussed.

PMID- 21723898
TI  - Definitions of histocompatibility typing terms: Harmonization of
      Histocompatibility Typing Terms Working Group.
AB  - Histocompatibility testing for stem cell and solid organ transplantation has
      become increasingly complex as newly discovered human leukocyte antigen (HLA)
      alleles are described. HLA typing assignments reported by laboratories are used
      by physicians and donor registries for matching donors and recipients. To
      communicate effectively, a common language for histocompatibility terms should be
      established. In early 2010, representatives from clinical, registry, and
      histocompatibility organizations joined together as the Harmonization of
      Histocompatibility Typing Terms Working Group to define a consensual language for
      laboratories, physicians and registries to communicate histocompatibility typing
      information. The Working Group defined terms for HLA typing resolution, HLA
      matching and a format for reporting HLA assignments. In addition, definitions of
      verification typing and extended typing were addressed. The original draft of the
      Definitions of Histocompatibility Typing Terms was disseminated to colleagues
      from each organization to gain feedback and create a collaborative document.
      Commentary gathered during this 90-day review period were discussed and
      implemented for preparation of this report. Histocompatibility testing continues
      to evolve thus, the definitions agreed upon today, likely will require refinement
      and perhaps additional terminology in the future.

PMID- 21723899
TI  - A systematic review of ETEC epidemiology focusing on colonization factor and
      toxin expression.
AB  - INTRODUCTION: Vaccine development for enterotoxigenic Escherichia coli (ETEC) is
      dependent on in-depth understanding of toxin and colonization factor (CF)
      distribution. We sought to describe ETEC epidemiology across regions and
      populations, focusing on CF and toxin prevalence. METHODS: We conducted a
      systematic review of the published literature, including studies reporting data
      on ETEC CF and toxin distributions among those with ETEC infection. Point
      estimates and confidence intervals were calculated using random effects models.
      RESULTS: Data on 17,205 ETEC isolates were abstracted from 136 included studies.
      Approximately half of the studies (49%) involved endemic populations, and an
      additional 17% involved only travel populations. Globally, 60% of isolates
      expressed LT either alone (27%) or in combination with ST (33%). CFA/I-expressing
      strains were common in all regions (17%), as were ETEC expressing CFA/II (9%) and
      IV (18%). Marked variation in toxins and CFs across regions and populations was
      observed. DISCUSSION/CONCLUSIONS: These results demonstrate the relative
      importance of specific CFs in achieving target product profiles for a future ETEC
      vaccine. However, heterogeneity across time, population, and region, confounded
      by variability in CF and toxin detection methodologies, obfuscates rational
      estimates for valency requirements.

PMID- 21723900
TI  - Antigen encoded by vaccine vectors derived from human adenovirus serotype 5 is
      preferentially presented to CD8+ T lymphocytes by the CD8alpha+ dendritic cell
      subset.
AB  - Different subsets of dendritic cells (DC) elicit qualitatively different immune
      responses. In mice, two lymphoid tissue-resident subsets, CD8alpha(+) and
      CD8alpha(-), have been implicated in the induction of T helper 1 (Th1) or Th2
      responses, respectively. Moreover, CD8alpha(+) DC appear to play a major role in
      priming CD8(+) T lymphocyte responses to viral antigens in the course of diverse
      viral infections. These considerations have been less extensively explored for
      vaccine vectors derived from viruses. Despite inefficient ex vivo transduction of
      DC, vectored vaccines derived from human adenoviruses of serotype 5 (Ad5) elicit
      robust immune responses, predominantly of the Th1 orientation, in humans and
      mice. At present it is unknown whether Ad5 interacts with DC subsets in a
      differential manner, thereby influencing the quality of the elicited IR. To
      address this issue, successive steps (attachment, transgene expression, MHC class
      I antigen presentation and activation of antigen-specific T lymphocytes) involved
      in induction of immune responses by Ad5-based vectors have been examined in
      CD8alpha(+) and CD8alpha(-) murine DC subsets. Although in both ex vivo and in
      vivo experiments CD8alpha(+) and CD8alpha(-) DC subsets captured an Ad5-based
      vector to a similar extent, transgene expression and subsequent MHC class I
      display of a transgene-encoded antigen were more efficient in CD8alpha(+) DC.
      Moreover, following in vivo and ex vivo transduction with an Ad5-based vaccine,
      antigen-specific CD8(+) T lymphocytes were more efficiently activated by
      CD8alpha(+) DC than by CD8alpha(-) DC. Thus, superior antigen expression and MHC
      class I display in CD8alpha(+) DC may contribute to preferred priming of antigen
      specific CD8(+) lymphocytes by Ad5-transduced CD8alpha(+) DC.

PMID- 21723901
TI  - Tumor-specific peptide-based vaccines containing the conformationally biased,
      response-selective C5a agonists EP54 and EP67 protect against aggressive large B
      cell lymphoma in a syngeneic murine model.
AB  - Vaccines to large B cell lymphoma were made by the covalent attachment of an
      epitope from the gp70 glycoprotein (SSWDFITV) to the N-termini of the
      conformationally biased, response-selective C5a agonists EP54 (YSFKPMPLaR) and
      EP67 (YSFKDMP(MeL)aR). Syngeneic Balb/c mice were immunized with these EP54/EP67
      containing vaccines and challenged with a lethal dose of the highly liver
      metastatic and gp70-expressing lymphoma cell line RAW117-H10 to evaluate the
      ability of these vaccines to induce protective immune outcomes. All mice
      immunized with SSWDFITVRRYSFKPMPLaR (Vaccine 2) and SSWDFITVRRYSFKDMP(MeL)aR
      (Vaccine 3) were protected to a lethal challenge of RAW117-H10 lymphoma (>170
      days survival) and exhibited no lymphoma infiltration or solid tumor nodules in
      the liver relative to unvaccinated controls (<18 days survival). Vaccines 2 and 3
      contained the protease-sensitive double-Arg (RR) linker sequence between the
      epitope and the EP54/EP67 moieties in order to provide a site for intracellular
      proteases to separate the epitope from the EP54/EP67 moieties once internalized
      by the APC and, consequently, enhance epitope presentation in the context of MHC
      I/II. These protected mice exhibited an immune outcome consistent with increased
      involvement of CD8(+) and/or CD4(+) T lymphocytes relative to controls and mice
      that did not survive or showed low survival rates as with Vaccines 1 and 4, which
      lacked the RR linker sequence. CD8(+) T lymphocytes activated in response to
      Vaccines 2 and 3 express cytotoxic specificity for gp70-expressing RAW117-H10
      lymphoma cells, but not antigen-irrelevant MDA-MB231A human breast cancer cells.
      Results are discussed against the backdrop of the ability of EP54/EP67 to
      selectively target antigens to and activate C5a receptor-bearing antigen
      presenting cells and the prospects of using such vaccines therapeutically against
      lymphoma and other cancers.

PMID- 21723902
TI  - Expected epidemiological impacts of introducing an HIV vaccine in Thailand: a
      model-based analysis.
AB  - BACKGROUND: The RV144 trial conducted in Thailand was the first to demonstrate
      modest protective efficacy of an HIV vaccine. Its estimated initial efficacy was
      ~74%, but this waned considerably over time. METHODS: We developed a mathematical
      model to reflect historical and current HIV trends across different at-risk
      populations in Thailand. The model was used to estimate the expected number of
      infections that would be averted if a vaccine with outcome characteristics
      similar to the RV144 vaccine was implemented in Thailand at varying levels of
      coverage. RESULTS: In the absence of a vaccine, we projected roughly 65,000 new
      HIV infections among adults during the period between 2011 and 2021. Due to the
      waning efficacy of the vaccine, vaccination campaigns were found to have modest
      long-term public health benefit unless re-vaccination occurred. We forecast that
      an RV144-like vaccine with coverage of 30% of the population would lead to a 3%
      reduction in HIV incidence during the next 10 years. In comparison, 30% coverage
      of annual or biennial re-vaccination with the vaccine was found to result in 23%
      and 14% reductions in incidence, respectively. Coverage of 60% without re
      vaccination resulted in a 7% reduction. Epidemiological outcomes were found to
      depend primarily on three factors: vaccination coverage, vaccine efficacy, and
      the duration of protection the vaccine provided. DISCUSSION: Due to the short
      duration of protection the vaccine provides without re-vaccination, our model
      predicts modest benefit from a vaccination campaign with an RV144-like HIV
      vaccine in Thailand. Annual or biannual re-vaccination is predicted to greatly
      increase the long-term public health benefits of a vaccination campaign. The
      feasibility of vaccine implementation, as well as its economic viability, remains
      to be determined.

PMID- 21723903
TI  - Plasma pharmacokinetics of melamine and a blend of melamine and cyanuric acid in
      rainbow trout (Oncorhynchus mykiss).
AB  - The objective of the study was to obtain pharmacokinetic parameters for melamine
      and blend of melamine (MEL) and cyanuric acid (CYA) in rainbow trout
      (Oncorhynchus mykiss). The single target dosage of MEL (20mg/kg bw) and the blend
      of MEL and CYA (5 and 1.67 mg/kg bw, respectively) were designed and plasma
      samples were collected at 30 min, 1, 4, 8, 12, 20, 24, 36, 48, 72, 144 and 240 h
      sequentially. An optimized method for simultaneous determination of MEL and CYA
      in plasma and animal tissues by LC-MS/MS was used. The data were shown to best
      fit a non-compartment model with first order processes of linear characters for
      melamine, with half-life (t(1/2)) of 32.2-32.9h, clearance (Cl(z/F)) of 35.9-36.6
      ml/h/kg, and volume of distribution (V(ss)) of 1.67-1.74 l/kg. Withdrawal of CYA
      was much more rapid than that of MEL with higher Cl(z/F) (783.56 ml/h/kg) and
      shorter t(1/2) (7.92 h). T(max) of MEL20 and MEL5 were 12 and 20 h, respectively,
      which showed that T(max) of MEL5 was delayed when MEL and CYA were given
      together. The results are quite different from those in mammals and showed much
      slower elimination of MEL and CYA from rainbow trout body.

PMID- 21723904
TI  - Support for down-tuning of the calreticulin gene in the process of human
      evolution.
AB  - Tissue-specific expression of the CALR gene in the brain gray matter in late
      adolescence and early adulthood coincides with the expression of the psychoses
      phenotypes. Indeed, increased expression of the chaperone genes in the prefrontal
      cortex has been reported in patients affected by schizophrenia. We have
      previously reported cases of psychosis-associated mutations in the CALR gene
      promoter. One of those mutations at -48 was found to increase the expression of
      the gene in comparison with the wild type sequence. A recently identified
      mutation at -220 reverts the conserved block harboring nucleotide -220 to the
      ancestral type, and has an approximate prevalence of 0.7% in psychoses. In this
      study, we analyzed the functional implication of this mutation in the human
      neuroblastoma cell line BE(2)-C, and non-neural Human Embryonic Kidney 293 (HEK
      293), and show that the -220A mutation results in a constitutive increase in the
      expression of the CALR gene (p<0.0003). We checked homology of the first 1000-bp
      CALR promoter sequence across species, and found that nucleotide -220C is the
      only human-unique nucleotide in that stretch. The -220A mutation, on the other
      hand, co-occurs with severe cognition deficit in humans, and is the rule across
      the species except humans. To our knowledge, the -220A mutation is the first
      reported instance of a cognition-deficit-associated mutation which reverses a
      human gene promoter to the primitive type. It may be speculated that, at least
      the basal transcription of the CALR gene, relating to the proximal promoter
      region, has been decreased during the process of evolution to humans.

PMID- 21723905
TI  - Patients with insomnia and subthreshold depression show marked worsening of
      insomnia after discontinuation of sleep promoting medication.
AB  - OBJECTIVE: To investigate whether the outcome of treatment with trazodone CR in
      primary insomnia differs between patients with and without subthreshold
      depression. METHODS: 14 patients (9 females, mean age 57.3 +/- 13.3) with primary
      insomnia and increased Beck Depression Inventory (BDI) scores (>10) and 15 sex-
      and age-matched patients with primary insomnia and low BDI scores (<= 10) were
      treated with trazodone CR 25-150 mg/d for 3 months and followed for 1 month after
      discontinuation of the medication. The Athens Insomnia Scale (AIS), Sheehan
      Disability Scale (SDS), and Clinical Global Impression scale (CGI) were completed
      at baseline, after each month of treatment and after the first week of run-out
      phase. Additional assessment tools comprised sleep diaries, the Leeds Sleep
      Evaluation Questionnaire (LSEQ) and actigraphic recordings. RESULTS: Subjective
      sleep time increased by 61.5 +/- 72.3 min in the group with low BDI and 60.0 +/-
      59.4 min in the group with increased BDI at the end of the treatment phase. The
      significant improvements were also observed in the AIS, CGI, LSEQ and SDS. During
      the run-out phase the improvement was sustained in patients with low BDI, while
      AIS scores, sleep latency and total sleep time deteriorated in patients with
      increased BDI. CONCLUSIONS: Patients with subthreshold depression, even if the
      depressive symptoms do not fulfill the time criteria for depressive episode, show
      marked worsening of insomnia after discontinuation of sleep promoting medication.

PMID- 21723906
TI  - Smoking and tardive dyskinesia in male patients with chronic schizophrenia.
AB  - Interactions between smoking and movement disorders include the contrasting
      associations of more cigarette smoking with reductions in Parkinson's disease and
      increases in tardive dyskinesia (TD) symptoms. Here we examine the relationship
      between smoking and TD in a large sample of inpatients with schizophrenia. We
      used cross-sectional naturalistic methods to analyze the prevalence and severity
      of neuroleptic-induced TD in relation to cigarette smoking among 764 male chronic
      and medicated inpatients meeting DSM-IV criteria for schizophrenia. We
      administered a detailed questionnaire including general information, medical and
      psychological conditions, and smoking behaviors. We evaluated TD severity using
      the abnormal involuntary movement scale (AIMS) and psychopathology using the
      Positive and Negative Syndrome Scale (PANSS). The main statistical analyses used
      cross-tabulations for the prevalence of TD by smoking and multivariate regression
      analyses for continuous measures (AIMS and PANSS). We found that the prevalence
      of TD did not significantly differ between smokers (41%=237/578) and non-smokers
      (37%=69/186). Secondary outcomes showed a significant association between the
      AIMS total score and age, duration of illness and hospitalization times. Thus,
      smoking was not associated with TD in male Chinese schizophrenics, but consistent
      with previous reports, older patients with a longer duration of illness and more
      hospitalizations showed greater severity of TD.

PMID- 21723907
TI  - Antioxidant and hepatoprotective activities of phenolic rich fraction of
      Seabuckthorn (Hippophae rhamnoides L.) leaves.
AB  - Present study was aimed to investigate antioxidant and hepatoprotective
      activities of phenolic rich fraction (PRF) of Seabuckthorn leaves on CCl(4)
      induced oxidative stress in Sprague Dawley rats. Total phenolic content was found
      to be 319.33 mg gallic acid equivalent (GAE)/g PRF and some of its phenolic
      constituents, such as gallic acid, myricetin, quercetin, kaempferol and
      isorhamnetin were found to be in the range of 1.935-196.89 mg/g of PRF as
      determined by reverse-phase high-performance liquid chromatography (RP-HPLC).
      Oral administration of PRF at dose of 25-75 mg/kg body weight significantly
      protected from CCl(4) induced elevation in aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) and bilirubin
      in serum, elevation in hepatic lipid peroxidation, hydroperoxides, protein
      carbonyls, depletion of hepatic reduced glutathione (GSH) and decrease in the
      activities of hepatic antioxidant enzymes; superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S
      transferase (GST). The PRF also protected against histopathological changes
      produced by CCl(4) such as hepatocytic necrosis, fatty changes, vacuolation, etc.
      The data obtained in the present study suggests that PRF has potent antioxidant
      activity, prevent oxidative damage to major biomolecules and afford significant
      protection against CCl(4) induced oxidative damage in the liver.

PMID- 21723908
TI  - Assessing the toxicity of polymeric food-contact substances.
AB  - The US Food and Drug Administration's Office of Food Additive Safety in the
      Center for Food Safety and Applied Nutrition conducts safety assessments of food
      additives, including food-contact substances such as polymeric and oligomeric
      materials that have the potential to migrate to food. Traditionally, little
      toxicity testing has been conducted on the low-molecular weight oligomeric
      fraction (< 1000 Da) of these food-contact substances. At lower exposures (<= 150
      MUg/person/day), safety has been assessed based on the use of toxicity data on
      the monomeric components of these polymers as a sufficiently conservative
      approach for addressing the concern for genetic toxicity and carcinogenicity of
      the low-molecular weight oligomers (LMWOs). This paper discusses this assumption
      relative to the available data on these substances and their monomeric components
      in the context of exposures of <= 150 MUg/person/day with emphasis on the
      evaluation of the potential genetic toxicity of these compounds. In most
      instances, data are available on either the monomers or the monomers' structural
      class to conservatively address the potential genetic toxicity of the LMWOs.
      Caveats to this generalization are also discussed. The assessment of LMWOs is
      important because they can be one of the primary migrants to food from a
      polymeric food-contact substance.

PMID- 21723909
TI  - Chemical characterization of Iraqi propolis samples and assessing their
      antioxidant potentials.
AB  - Propolis samples, collected from different geographical locations in Iraq
      (Baghdad, Dahuk, Mosul and Salah ad-Din), were analyzed and assessed for their
      anti-oxidant activity. Concentrations of phenolic compounds (flavonoids, phenolic
      acids and their esters) in propolis were estimated using high performance liquid
      chromatography coupled to electrospray mass spectrometry. Thirty-eight different
      compounds were identified and 33 of them were polyphenols. Other compounds were
      tentatively identified as clerodane diterpenoids, and one was considered unknown.
      Semi-quantitative measurements showed that phenolic acids and their esters were
      the predominant constituents in propolis extracts, followed by flavones and
      flavonols, and then flavanones and dihydroflavonols. Propolis samples were
      further spectrophotometrically characterized using the Folin-Ciocalteu reagent
      for the determination of total phenolic compounds. The free radical scavenging
      activities of propolis samples were also evaluated by using the 2,2-diphenyl-1
      picrylhydrazyl assay. The results revealed that propolis extracts exhibited
      strong free radical scavenging activity.

PMID- 21723910
TI  - Cytoprotective activity against peroxide-induced oxidative damage and
      cytotoxicity of flavonoids in C6 rat glioma cells.
AB  - The aim of this study was to investigate the relationship between cytoprotective
      and cytotoxic activities of selected plant flavonoids in C6 glioma cells.
      Apigenin, kaempferol, luteolin, and quercetin were cytotoxic at low MUM
      concentrations (LOECs: 5-20 MUM), whereas myricetin was less toxic (LOEC>20 MUM).
      Cytotoxicity was not due to H(2)O(2) generation from flavonoids in culture
      medium. Quercetin, luteolin, and kaempferol protected the cells from peroxide
      induced cytotoxicity. Concentration-effect curves for cytoprotection had a
      biphasic shape. In contrast, apigenin and myricetin did not exhibit any
      cytoprotective activity. The first three compounds also inhibited cellular lipid
      peroxidation induced by CHP, while the latter were ineffective. Importantly,
      concentrations of luteolin and kaempferol protecting cells under oxidative stress
      were identical to those causing cell damage under normal conditions. Only in case
      of quercetin there was a narrow range of concentrations protecting cells without
      being cytotoxic to non-stressed cells. Thus, even for flavonoids with a high
      antioxidant capacity in cell-free systems the cytoprotective selectivity
      (LOEC(cytotox)/LOEC(cytoprot)) was very low or even absent. These results should
      be taken into account when the prophylactic or therapeutic application of
      flavonoids as antioxidants is discussed.

PMID- 21723911
TI  - Cadmium induces differentiation of RAW264.7 cells into osteoclasts in the
      presence of RANKL.
AB  - The mechanism of cadmium effects on bone is not fully understood. In this study,
      we investigated the effects of cadmium on osteoclasts differentiation and the
      probable mechanism. RAW264.7 cells were exposed to cadmium (0-60 nmol/L) in the
      presence or absence of receptor-activated nuclear factor kappa B ligand (RANKL)
      for 5 days. Then, the viability, tartrate-resistant acid phosphatase (TRAP)
      activity and the formation of TRAP positive multinucleated osteoclasts were
      observed. Receptor activator of nuclear factor kappa B (RANK), tumor necrosis
      factor receptor associated factor 6 (TRAF6), c-src, c-fos, fos-related antigen 1
      (Fra1) expression were determined by reverse transcription polymerase chain
      reaction. Cadmium increased TRAP activity (20-40%) and TRAP positive cell
      formation in the presence of RANKL, but had no obvious influence on them without
      RANKL. RANK, TRAF6, Fra1, c-src and c-fos (at 15-30 nmol/L) expression were
      enhanced (30-70%) by cadmium in the presence of RANKL, but cadmium had little
      influence on them in the absence of RANKL. This study demonstrated that cadmium
      could induce differentiation of osteoclasts precursor into osteoclasts in the
      presence of RANKL. Even though the changes of gene expression were small,
      RANKL/RANK and downstream genes may play an important role in cadmium effects on
      osteoclasts.

PMID- 21723912
TI  - The molecular interaction between the glutamatergic, noradrenergic, dopaminergic
      and serotoninergic systems informs a detailed genetic perspective on depressive
      phenotypes.
AB  - The glutamatergic pathway has been consistently involved in the physiopathology
      of depressive disorder. However a complete dissection and integration of its role
      in the context of other known mechanisms is lacking. We summarized and integrated
      the evidence of various levels of interaction between glutamatergic and
      monoaminergic pathways (see videos). We identified six molecular pathways, some
      of which with specific regional distribution within the brain. From the six
      pathways we identified the key proteins and their coding genes, we then provided
      a detailed list of possible candidates with practical suggestions for association
      studies planning.

PMID- 21723913
TI  - L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease?
AB  - There is consensus that amelioration of the motor symptoms of Parkinson's disease
      is most effective with L-DOPA (levodopa). However, this necessary therapeutic
      step is biased by an enduring belief that L-DOPA is toxic to the remaining
      substantia nigra dopaminergic neurons by itself, or by specific metabolites such
      as dopamine. The concept of L-DOPA toxicity originated from pre-clinical studies
      conducted mainly in cell culture, demonstrating that L-DOPA or its derivatives
      damage dopaminergic neurons due to oxidative stress and other mechanisms.
      However, the in vitro data remain controversial as some studies showed
      neuroprotective, rather than toxic action of the drug. The relevance of this
      debate needs to be considered in the context of the studies conducted on animals
      and in clinical trials that do not provide convincing evidence for L-DOPA
      toxicity in vivo. This review presents the current views on the pathophysiology
      of Parkinson's disease, focusing on mitochondrial dysfunction and
      oxidative/proteolytic stress, the factors that can be affected by L-DOPA or its
      metabolites. We then critically discuss the evidence supporting the two opposing
      views on the effects of L-DOPA in vitro, as well as the animal and human data. We
      also address the problem of inadequate experimental models used in these studies.
      L-DOPA remains the symptomatic 'hero' of Parkinson's disease. Whether it
      contributes to degeneration of nigral dopaminergic neurons, or is a 'scapegoat'
      for explaining undesirable or unexpected effects of the treatment, remains a
      hotly debated topic.

PMID- 21723915
TI  - Rottlerin dissolves pre-formed protein amyloid: a study on hen egg white
      lysozyme.
AB  - BACKGROUND: Deposition of protein fibrillar aggregates called amyloids in the
      tissue, is the principal cause of several degenerative diseases. Here, we have
      shown the disaggregation potential of rottlerin towards hen egg white lysozyme
      (HEWL) fibrils formed under alkaline conditions (pH-12.2). METHODS: Several
      biophysical methods like Atomic force microscopy (AFM), Fourier transform
      infrared spectroscopy (FTIR) and fluorescence emission spectra were used for the
      study. RESULTS AND CONCLUSION: Rottlerin exhibited instantaneous disaggregation
      effect on HEWL fibrils as monitored by Thioflavin T assay, anisotropy study and
      AFM imaging. Further we have monitored the conformational changes induced by
      rottlerin on the fibril in terms of surface hydrophobicity and secondary
      structure through 8-anilino-1-naphthalene sulfonic acid (ANS) fluorescence and
      FTIR study respectively. We have also attempted to elucidate the type of
      interaction between HEWL and rottlerin at pH-12.2 employing techniques like
      quenching study and FTIR. GENERAL SIGNIFICANCE: Rottlerin seems to have potential
      application as anti-amyloid compound.

PMID- 21723914
TI  - Mineralocorticoid receptors in vascular function and disease.
AB  - The mineralocorticoid receptor (MR), a member of the steroid receptor family,
      regulates blood pressure by mediating the effects of the hormone aldosterone
      (Aldo) on renal sodium handling. Over the past decade, it has become clear that
      MR is expressed in the cardiovascular system and interest has grown in
      understanding the direct role of the MR in regulating vascular function and
      contributing to cardiovascular disease. This interest stems from multiple
      clinical studies in which drugs that decrease MR activation also reduce the
      incidence of heart attacks, strokes, and mortality out of proportion to modest
      changes in systemic blood pressure. The presence of functional mineralocorticoid
      receptors in vascular smooth muscle and endothelial cells is now well established
      and, while still controversial, data supports the vasculature as an Aldo
      responsive tissue. This review summarizes recent advances in our understanding of
      the role of vascular MR in regulating normal vascular function and in promoting
      vascular disease. In vitro data, in vivo animal studies, and human data are
      reviewed suggesting a role for MR-activation in promoting vascular oxidative
      stress, inhibiting vascular relaxation, and contributing to vessel inflammation,
      fibrosis, and remodeling. These detrimental vascular effects of MR activation
      appear to be independent of changes in blood pressure and are synergistic with
      the presence of endothelial dysfunction or damage. Thus, in humans with
      underlying cardiovascular disease or cardiovascular risk factors, vascular MR
      activation may promote vascular aging and atherosclerosis thereby contributing to
      the pathophysiology of heart attack, stroke, and possibly even hypertension.
      Further exploration of the molecular mechanisms for the detrimental vascular
      effects of MR activation has the potential to identify novel therapeutic targets
      to prevent or treat common cardiovascular disorders.

PMID- 21723916
TI  - The induction of human CL-P1 expression in hypoxia/reoxygenation culture
      condition and rat CL-P1 after ischemic/reperfusion treatment.
AB  - BACKGROUND: Oxidative stress-induced endothelial dysfunction and oxidized low
      density lipoprotein (LDL) might play a key role in the pathogenesis of
      atherosclerosis. We recently identified a vascular endothelial scavenger
      receptor, collectin placenta 1 (CL-P1), which acts as a receptor for oxidized LDL
      as well as for microbes. METHODS: We demonstrate how hypoxic and oxidative stress
      induced CL-P1 expression and compared their effects with the expression of lectin
      like oxidized low-density lipoprotein receptor 1 (LOX-1), an endothelial
      scavenger receptor expressed by oxidative stress. RESULTS: Hypoxia/reoxygenation
      induced CL-P1 mRNA and protein expression in human umbilical vein endothelial
      cells (HUVECs). The expression of LOX-1 mRNA in these cells peaked slightly at 24
      h, while the expression of CL-P1 had an onset at 72 h and was sustained for 120 h
      after reoxygenation. Furthermore, the exposure of rat carotid artery endothelium
      to ischemia/reperfusion increased the maximal CL-P1 mRNA expression at 72 h and
      expression of its protein peaked at 7 days after this treatment. We demonstrate
      that CL-P1 up-regulation is induced in vitro and in vivo by oxidative stress.
      GENERAL SIGNIFICANCE: The inducible expression of CL-P1 by oxidative stress might
      play a crucial role in endothelial dysfunction or chronic activation leading to
      the pathogenesis of atherosclerosis.

PMID- 21723917
TI  - Mannose 6-phosphate receptor homology (MRH) domain-containing lectins in the
      secretory pathway.
AB  - BACKGROUND: The mannose 6-phosphate receptor homology (MRH) domain-containing
      family of proteins, which include recycling receptors (mannose 6-phosphate
      receptors, MPRs), resident endoplasmic reticulum (ER) proteins (glucosidase II
      beta-subunit, XTP3-B, OS-9), and a Golgi glycosyltransferase (GlcNAc
      phosphotransferase gamma-subunit), are characterized by the presence of one or
      more MRH domains. Many MRH domains act as lectins and bind specific
      phosphorylated (MPRs) or non-phosphorylated (glucosidase II beta-subunit, XTP3-B
      and OS-9) high mannose-type N-glycans. The MPRs are the only proteins known to
      bind mannose 6-phosphate (Man-6-P) residues via their MRH domains. SCOPE OF
      REVIEW: Recent biochemical and structural studies that have provided valuable
      insight into the glycan specificity and mechanisms of carbohydrate recognition by
      this diverse group of MRH domain-containing proteins are highlighted. MAJOR
      CONCLUSIONS: Currently, three-dimensional structures are known for ten MRH
      domains, revealing the conservation of a similar fold. OS-9 and the MPRs use the
      same four residues (Gln, Arg, Glu, and Tyr) to bind mannose. GENERAL
      SIGNIFICANCE: The MRH domain-containing proteins play key roles in the secretory
      pathway: glucosidase II, XTP3-B, and OS-9 are involved in the recognition of
      nascent glycoproteins, whereas the MPRs play an essential role in lysosome
      biogenesis by targeting Man-6-P-containing lysosomal enzymes to the lysosome.

PMID- 21723918
TI  - Intrinsic dynamics and synaptic inputs control the activity patterns of
      subthalamic nucleus neurons in health and in Parkinson's disease.
AB  - Neurons in the subthalamic nucleus occupy a pivotal position in the circuitry of
      the basal ganglia. They receive direct excitatory input from the cerebral cortex
      and the intralaminar nuclei of the thalamus, and directly excite the inhibitory
      basal ganglia output neurons in the internal segment of the globus pallidus and
      the substantia nigra. They are also engaged in a reciprocal synaptic arrangement
      with inhibitory neurons in the external segment of the globus pallidus. Although
      once viewed as a simple relay of extrinsic input to the basal ganglia,
      physiological studies of subthalamic neurons have revealed that activity in these
      neurons does not directly reflect their pattern of extrinsic excitation.
      Subthalamic neurons are autonomously active at rates comparable to those observed
      in vivo, and they generate complex patterns of intrinsic activity arising from
      the interactions between voltage sensitive ion channels on the somatodendritic
      and axonal membranes. Extrinsic synaptic excitation does not create the firing
      pattern of the subthalamic neuron, but rather controls the timing of action
      potentials generated intrinsically. The dopaminergic innervation of the
      subthalamic nucleus, although moderate, can directly influence firing patterns by
      acting both on synaptic transmission and voltage-sensitive ion channels
      responsible for intrinsic properties. Furthermore, chronic dopamine depletion in
      Parkinson's disease may modify both synaptic transmission and integration in the
      subthalamic nucleus, in addition to its effects on other regions of the basal
      ganglia.

PMID- 21723920
TI  - Effects of chronic immobilization stress on anxiety-like behavior and basolateral
      amygdala morphology in Fmr1 knockout mice.
AB  - Several lines of clinical evidence support the idea that fragile X syndrome (FXS)
      may involve a dysregulation of hypothalamic-pituitary-adrenal axis function
      [Wisbeck et al. (2000) J Dev Behav Pediatr 21:278-282; Hessl et al. (2002)
      Psychoneuroendocrinology 27:855-872]. We had tested this idea in a mouse model of
      FXS (Fmr1 KO) and found that the hormonal response to acute stress was similar to
      that of wild-type (WT) mice [Qin and Smith (2008) Psychoneuroendocrinology 33:883
      889]. We report here responses to chronic stress (CS) in Fmr1 KO mice. Following
      restraint for 120 min/d, 10 consecutive days, we assessed dendrite and spine
      morphology in basolateral amygdala (BLA). We also monitored behavior in an
      elevated plus maze (EPM) and the hormonal response to this novel spatial
      environment. After CS, mice of both genotypes underwent adrenal hypertrophy, but
      effects were greater in WT mice. Behavior in the EPM indicated that only WT mice
      had the expected increase in anxiety following CS. Serum corticosterone and
      adrenocorticotropic hormone (ACTH) levels were both increased following the
      spatial novelty of EPM, and there were no differences between genotypes in the
      hormonal responses. BLA dendritic branching increased proximal to the soma in WT,
      but in Fmr1 KO mice branching was unaffected close to the soma and slightly
      decreased at one point distal to the soma. Similarly, spine density on apical and
      basal dendrites increased in WT but decreased in Fmr1 KO mice. Spine length on
      apical and basal dendrites increased in WT but was unaffected in Fmr1 KO mice.
      These differences in behavioral response and effects on neuron morphology in BLA
      suggest a diminished adaptive response of Fmr1 KO mice.

PMID- 21723921
TI  - Shaping of action potentials by type I and type II large-conductance Ca2+
      activated K+ channels.
AB  - The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping
      action potential waveforms in many types of neurons. Type II BK channels are
      differentiated from type I channels by their pharmacology and slow gating
      kinetics. The beta4 accessory subunit confers type II properties on BK alpha
      subunits. Empirically derived properties of BK channels, with and without the
      beta4 accessory subunit, were obtained using a heterologous expression system
      under physiological ionic conditions. These data were then used to study how BK
      channels alone (type I) and with the accessory beta4 subunit (type II) modulate
      action potential properties in biophysical neuron models. Overall, the models
      support the hypothesis that it is the slower kinetics provided by the beta4
      subunit that endows the BK channel with type II properties, which leads to
      broadening of action potentials and, secondarily, to greater recruitment of SK
      channels reducing neuronal excitability. Two regions of parameter space
      distinguished type II and type I effects; one where the range of BK-activating
      Ca(2+) was high (>20 MUM) and the other where BK-activating Ca(2+) was low (~0.4
      1.2 MUM). The latter required an elevated BK channel density, possibly beyond a
      likely physiological range. BK-mediated sharpening of the spike waveform
      associated with the lack of the beta4 subunit was sensitive to the properties of
      voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We
      also found that depending on Ca(2+) dynamics, type II BK channels may have the
      ability to contribute to the medium AHP, a property not generally ascribed to BK
      channels, influencing the frequency-current relationship. Finally, we show how
      the broadening of action potentials conferred by type II BK channels can also
      indirectly increase the recruitment of SK-type channels decreasing the
      excitability of the neuron.

PMID- 21723919
TI  - Pathological basal ganglia activity in movement disorders.
AB  - Our understanding of the pathophysiology of movement disorders and associated
      changes in basal ganglia activities has significantly changed during the last few
      decades. This process began with the development of detailed anatomical models of
      the basal ganglia, followed by studies of basal ganglia activity patterns in
      animal models of common movement disorders and electrophysiological recordings in
      movement disorder patients undergoing functional neurosurgical procedures. These
      investigations first resulted in an appreciation of global activity changes in
      the basal ganglia in parkinsonism and other disorders, and later in the detailed
      description of pathological basal ganglia activity patterns, specifically burst
      patterns and oscillatory synchronous discharge of basal ganglia neurons. In this
      review, we critically summarize our current knowledge of the pathological
      discharge patterns of basal ganglia neurons in Parkinson's disease, dystonia, and
      dyskinesias.

PMID- 21723922
TI  - Calpain inhibition protected spinal cord motoneurons against 1-methyl-4
      phenylpyridinium ion and rotenone.
AB  - Parkinson's disease (PD), characterized by selective midbrain nigrostriatal
      dopaminergic degeneration, is consistently associated with moderate systemic
      mitochondrial dysfunction. Downstream degeneration of spinal cord has also been
      suggested in PD, although the mechanisms have not been much investigated. In the
      present study, two mitochondrial toxicants, 1-methyl-4-phenylpyridinium ion
      (MPP(+)) and rotenone were tested in ventral spinal cord (VSC 4.1) motoneuronal
      cells. Cell death was assessed by morphological and biochemical means to discern
      a lower apoptosis-inducing concentration and lethal concentration of 50% cell
      death (LC(50)), which were subsequently compared in further cytoprotection
      experiments. Mitochondrial toxicants dose-dependently induced increase in
      intracellular free Ca(2+) level, which was conducive for increased expression and
      activities of Ca(2+)-activated neutral protease calpain and downstream caspase-3.
      Thus, mitochondrial damage triggered apoptotic mechanisms in spinal cord
      motoneurons. Inhibition of calpain by calpeptin significantly attenuated damaging
      effects of MPP(+) and rotenone on motoneurons, especially at low apoptosis
      inducing concentrations of toxicants and partly at their LC(50), as demonstrated
      by absence of DNA ladder formation and decrease in terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells.
      Cytoprotection by calpeptin was observed with marked decreases in Bax: Bcl-2
      ratio and activities of calpain and caspase-3, which affirmed the role of
      mitochondrial dysfunction and involvement of intrinsic pathway in mediation of
      apoptosis. These findings strongly suggested that parkinsonian toxicants MPP(+)
      and rotenone at low doses induced cascade of cell-damaging effects in spinal cord
      motoneurons, thus, highlighting the possibility of induction of apoptotic
      mechanisms in these cells, when subjected to mitochondrial stress. Cytoprotection
      rendered by calpeptin further validated the involvement of calpain in apoptosis
      and suggested calpain inhibition as a potential neuroprotective strategy.

PMID- 21723923
TI  - Metabotropic glutamate receptor 5 promotes proliferation of human neural
      stem/progenitor cells with activation of mitogen-activated protein kinases
      signaling pathway in vitro.
AB  - Metabotropic glutamate receptors (mGluRs) regulate neurogenesis in brain, but the
      mechanisms remain unknown. In this study, we investigated the effect of mGluR5 on
      the proliferation of human embryonic neural stem/progenitor cells (NPCs), the
      expression of cyclin D1 and the activation of signaling pathways of mitogen
      activated protein kinases (MAPKs). Results showed that mGluR5 agonist (S)-3,5
      dihydroxyphenylglycine hydrate (DHPG) increased the proliferation of NPCs by
      increasing cell activity, diameter of neurospheres and cell division, while
      mGluR5 siRNA and antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride
      (MPEP) decreased the NPC proliferation. The mRNA and protein expressions of
      cyclin D1 increased with DHPG treatment and decreased after siRNA or MPEP
      treatment. It was also found that activation of extracellular signal-regulated
      protein kinase (ERK) and c-Jun N-terminal protein kinase (JNK) signaling pathways
      were involved in the proliferation of NPCs. After DHPG treatment, p-ERK1/2 and p
      JNK2 levels increased, and meanwhile p-p38 level decreased; but p-ERK1/2 and p
      JNK2 levels decreased after siRNA or MPEP treatment, and p-p38 level increased.
      Our findings demonstrated that mGluR5 promoted the proliferation of human
      embryonic cortical NPCs and increased cyclin D1 expression with the changes in
      phosphorylation of MAPKs signaling pathways in vitro, suggesting a novel
      mechanism for pharmacological study of treatment for ischemic brain injury and
      neurodegenerative disorders.

PMID- 21723924
TI  - Progressive centralization of midbrain hyperactivity after acoustic trauma.
AB  - Partial hearing loss is known to cause increased spontaneous activity at several
      stages of the central auditory pathways, and this phenomenon has been suggested
      as a possible neural substrate for tinnitus, a phantom hearing sensation. One
      recent study in guinea pig has suggested that approximately 6 weeks after
      acoustic trauma, the increased spontaneous activity in inferior colliculus is not
      intrinsically generated in the central nucleus but is dependent on afferent input
      from the cochlea. This was unexpected in view of the fact that tinnitus in human
      patients can persist after severing of the auditory nerve. In this study, we show
      that when recovery time after acoustic trauma is extended to 8 and 12 weeks,
      cochlear ablation does not significantly decrease the increased spontaneous
      activity measured in the inferior colliculus. This result demonstrates for the
      first time that central hyperactivity that develops after acoustic trauma
      transitions from an early stage when it is dependent on continued peripheral
      afferent input to a later stage in which the hyperactivity is intrinsically
      generated within the central nervous system.

PMID- 21723925
TI  - Posterior hypothalamic nucleus deep brain stimulation restores locomotion in rats
      with haloperidol-induced akinesia but not skilled forelimb use in pellet reaching
      and lever pressing.
AB  - Recent studies have shown that electrical stimulation of the posterior
      hypothalamic nucleus (PH) facilitates locomotion in control rats, and rats were
      made akinetic by dopaminergic blockade via haloperidol or dopamine depletion by
      the neurotoxin 6-hydroxydopamine. These findings suggest that PH stimulation
      might be a promising treatment for akinesia associated with dopamine loss in
      Parkinson's disease. The present study further examined the positive effects of
      PH stimulation on behavior by characterizing its potential facilitatory effects
      on tasks that require skilled movements. Rats were trained to reach for food
      pellets with a forelimb (skilled reaching) or press a bar in an operant
      conditioning task for food. PH stimulation in undrugged rats not only facilitated
      locomotion in each of the tasks, but also impaired performance of the skilled
      movement components of the tasks. Haloperidol reduced locomotion and skilled
      movement, and PH stimulation only restored locomotion. The results are discussed
      in relation to the idea that PH stimulation selectively facilitates locomotor
      behavior and may have limited use in restoring impairments in skilled movements
      and consummatory behavior that results from dopaminergic depletion.

PMID- 21723926
TI  - Increased interactions between PKA and NF-kappaB signaling in the hippocampus
      following loss of cholinergic input.
AB  - Neuropsychiatric disorders such as depression are frequently associated with
      Alzheimer's disease (AD) and the degeneration of cholinergic basal forebrain
      neurons and reductions in acetylcholine that occur in AD have been identified as
      potential mediators of these secondary neuropsychiatric symptomologies. Indeed,
      removal of cholinergic innervation to the hippocampus via selective immunolesions
      of septohippocampal cholinergic neurons induces dysfunction of the hypothalamic
      pituitary-adrenocortical (HPA) axis and decreases glucocorticoid receptor
      expression (GR). A subsequent study showed that loss of cholinergic input
      decreases the activity of the catalytic subunit of protein kinase A (PKAc) and
      lessens the interaction of protein kinase A (PKA) with GR. Because cross-coupling
      between nuclear factor-kappaB (NF-kappaB) p65 and GR depends on PKA signaling,
      the present study was conducted to evaluate the status of NF-kappaB as well as
      interactions of PKA with NF-kappaB in the hippocampus following cholinergic
      denervation. Expression of cytosolic NF-kappaB p65 was diminished and IkappaB was
      degraded in the hippocampus of cholinergic immunolesioned rats compared to the
      controls. Immunolesions also increased NF-kappaB p65 Ser276 phosphorylation, as
      well as interactions between PKAc and NF-kappaB p65. These results indicate that
      loss of cholinergic input to the hippocampus results in decreased PKA activity
      and increased NF-kappaB activity. Such altered signaling may contribute to
      psychiatric symptoms, including depression, in patients with AD.

PMID- 21723927
TI  - Mouse Fem1b interacts with and induces ubiquitin-mediated degradation of Ankrd37.
AB  - Ankyrin repeat domain 37 (Ankrd37), a protein containing ankyrin repeats (ARs)
      and a putative nuclear localization signal (NLS), is highly conserved from
      zebrafish to humans. In mouse testes, Ankrd37 protein was initially present in
      the cytoplasm of elongating spermatids, and finally restricted to the nuclei of
      spermatozoa during spermatogenesis. Ankrd37 bound to feminization 1 homolog b
      (Fem1b) as indicated by yeast two-hybrid screening and co-immunoprecipitation
      assays. Ankrd37 facilitated the transport of Fem1b protein from cytoplasm to
      nuclei in co-transfected CHO cells. In addition, the protein level of Ankrd37 was
      decreased in a Fem1b dose-dependent manner as shown by the transfection
      experiments, and Ankrd37 was ubiquitinated in the presence of Fem1b. As the
      nematode Fem-1 has been shown to target its downstream effector TRA-1 for
      ubiquitin-mediated degradation, we report in the present study that mouse Fem1b
      targets Ankrd37 for degradation in the same manner.

PMID- 21723928
TI  - Kinetic modelling of in vitro cell-based assays to characterize non-specific
      bindings and ADME processes in a static and a perfused fluidic system.
AB  - Recently, physiologically based perfusion in vitro systems have been developed to
      provide cell culture environment close to in vivo cell environment (e.g., fluidic
      conditions, organ interactions). In this work, we model and compare the fate of a
      chemical, benzo[a]pyrene (B[a]P), in a perfusion and a standard (static well
      plate) system. These in vitro systems are composed of Caco-2 and HepG2 cells so
      as to mimic absorption across the small intestine and intestinal and hepatic
      metabolism. Compartmental models were developed and calibrated with B[a]P
      kinetics data in the culture medium to estimate the apparent permeability of Caco
      2 cells, the in vitro biotransformation of B[a]P, as well as the different routes
      of loss by non-specific adsorption. Our results show that non-specific binding is
      the main process responsible for the depletion of B[a]P in the culture media: at
      steady state, only 40% and 24% of the total concentration of B[a]P are
      bioavailable in the static and perfused systems, respectively. We also showed
      that Caco-2 permeability in the perfused culture system is closer to in vivo
      conditions than the one obtained in the static system and that higher cellular
      metabolic activities are observed in static conditions. Perfused in vitro systems
      combined with kinetic modelling are promising tools for studying in vitro the
      different processes involved in the toxicokinetics of xenobiotics.

PMID- 21723929
TI  - N-Succinyl-chitosan systems for 5-aminosalicylic acid colon delivery: in vivo
      study with TNBS-induced colitis model in rats.
AB  - 5-Aminosalicylic acid (5-ASA) loaded N-Succinyl-chitosan (SucCH) microparticle
      and freeze-dried system were prepared as potential delivery systems to the colon.
      Physicochemical characterization and in vitro release and swelling studies were
      previously assessed and showed that the two formulations appeared to be good
      candidates to deliver the drug to the colon. In this work the effectiveness of
      these two systems in the treatment of inflammatory bowel disease was evaluated.
      In vitro mucoadhesive studies showed excellent mucoadhesive properties of both
      the systems to the inflamed colonic mucosa. Experimental colitis was induced by
      rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into male
      Wistar rats. Colon/body weight ratio, clinical activity score system,
      myeloperoxidase activity and histological evaluation were determined as
      inflammatory indices. The two formulations were compared with drug suspension and
      SucCH suspension. The results showed that the loading of 5-ASA into SucCH polymer
      markedly improved efficacy in the healing of induced colitis in rats.

PMID- 21723930
TI  - Evaluation of skin permeation and anti-inflammatory and analgesic effects of new
      naproxen microemulsion formulations.
AB  - The aim of this study was to evaluate the potential application of microemulsions
      as a transdermal drug delivery for naproxen (Np). The pseudo-ternary phase
      diagrams were developed for microemulsions composed of isopropyl myristate, Span
      80, Labrafil M, Labrasol, and Cremophor EL, ethanol and isopropyl alcohol and
      0.5N sodium hydroxide. The final concentration of Np in microemulsion systems was
      10% (w/w). The microemulsions were characterised by conductivity, droplet size,
      viscosity and pH. Moreover, in vitro permeability studies were performed using
      diffusion cells from rat skin. The permeation rates of Np from microemulsions
      (M1(Np) and M2(Np)) were higher than the commercial (C) gel formulation. The paw
      oedema test was performed in rats to evaluate the anti-inflammatory activity of
      Np. The volume increase in paw oedema after 6hr was 0.71+/-0.46% with M2(Np),
      whereas M1(Np) and C exhibited 6.48+/-2.71% and 14.97+/-3.15% increases in
      oedema, respectively. Additionally, a significant analgesic effect was detected
      in the hot plate and tail-flick tests for all test microemulsion and C
      formulations when compared with the control. Histopathological examination of the
      treated skin was performed to investigate changes in skin morphology. In
      conclusion, the microemulsion formulations, especially the M2(Np) formulation,
      may be used as an effective alternative for the transdermal delivery of Np.

PMID- 21723931
TI  - Formulation issues associated with transdermal fentanyl delivery.
AB  - Supersaturation has previously been studied as a mechanism to enhance membrane
      transport of fentanyl from propylene glycol:water formulations (PG:H(2)O) across
      silicone. In this study these supersaturated fentanyl formulations were evaluated
      in human skin. A number of polymers were also screened for their ability to
      stabilise the supersaturated formulations and permeation was evaluated for both
      infinite and finite doses. For infinite dose studies, permeation in skin
      increased linearly with increasing degree of drug saturation (DS) for
      formulations containing 0.5, 1, 2 DS of fentanyl and a 3 DS formulation
      stabilised with 1% (w/v) hydroxypropylcellulose (HPC). An excellent correlation
      was obtained for flux values in silicone compared with flux values in skin, for
      infinite dose studies for formulations containing 0.5, 1, 2 DS of fentanyl and
      the 3 DS formulation stabilised HPC. The concentration of the fentanyl in the
      stratum corneum also increased in proportion to the DS. However the same trend
      was not observed for finite dose studies. This is because the depletion of the
      solvent carrier promotes drug crystallisation with consequent implications for
      membrane transport. Tape-stripping experiments indicated that supersaturation of
      the drug is maintained in the outer layers of the stratum corneum. The ideal
      vehicle must, therefore, maintain the drug in solution on and in the skin in a
      sustained manner for effective transdermal delivery.

PMID- 21723932
TI  - Introduction: spiral ganglion neurons.

PMID- 21723933
TI  - Stimulation of bioprocesses by ultrasound.
AB  - Ultrasound (US) has become a ubiquitous technological process in a large variety
      of scientific disciplines. However, little information exists on the use of
      ultrasound to enhance biological processes and/or processing and consequently
      this paper provides an overview of work reported to date on this topic. This
      review provides a brief introduction to ultrasound and the history of ultrasound
      as applied to bioprocesses. This is followed by a discussion of the influence of
      US on discrete enzyme systems, enzymes used in bioremediation, microbial
      fermentations and enzymatic hydrolysis of biopolymers. Augmentation of anaerobic
      digestion by US is then considered along with enhancement of enzymes in food
      science and technology. The use of ultrasonically stimulated enzymes in synthesis
      is then considered and other relevant miscellaneous topics are described. It is
      concluded that the precise mechanism of action of US in bio-processing remains to
      be elucidated though a variety of plausible suggestions are made.

PMID- 21723934
TI  - Oxidative stress is implicated in arsenic-induced neural tube defects in chick
      embryos.
AB  - The potential of arsenic to induce neural tube defects (NTDs) remains a topic of
      controversy. In our previous study, oxidative stress and altered DNA methylation
      were observed in arsenic-exposed animal models. However, the correlation between
      these conditions was not fully understood. Therefore, our present aim was to
      determine whether arsenic exposure results in altered reactive oxygen species
      levels that affect DNA methylation and may contribute to NTDs in chick embryos.
      We demonstrated that arsenic-induced NTDs were associated with oxidative stress.
      Increased intracellular oxidative species and DNA methylation changes were
      observed following arsenic exposure. These changes were accompanied by a decrease
      in manganese superoxide dismutase activity. Furthermore, a significant decrease
      in DNA methyltransferase (DNMT) 1 and 3a expression was observed following
      arsenic exposure. The known antioxidant N-acetyl-l-cysteine, a known antioxidant,
      ameliorated global DNA hypomethylation and the decreased DNMT 1 and 3a expression
      observed during arsenic exposure. In addition, arsenic caused a significant
      decrease in S-adenosylmethionine (SAM) and significant increase in S
      adenosylhomocysteine (SAH). This effect resulted in a significant reduction of
      the SAM/SAH ratio, which may also contribute to DNA hypomethylation. In
      conclusion, oxidative stress and reduction in SAM/SAH ratio during arsenic
      exposure in chick embryos seem to modulate DNA methylation and contribute to
      arsenic-induced NTDs via epigenetic mechanisms.

PMID- 21723935
TI  - Brain energy metabolism is activated after acute and chronic administration of
      fenproporex in young rats.
AB  - Obesity is a chronic disease of multiple etiologies, including genetic,
      metabolic, environmental, social, and other factors. Pharmaceutical strategies in
      the treatment of obesity include drugs that regulate food intake, thermo genesis,
      fat absorption, and fat metabolism. Fenproporex is the second most commonly
      consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in
      vivo into amphetamine. Studies suggest that amphetamine induces neurotoxicity
      through generation of free radicals and mitochondrial apoptotic pathway by
      cytochrome c release, accompanied by a decrease of mitochondrial membrane
      potential. Mitochondria are intracellular organelles that play a crucial role in
      ATP production. Thus, in the present study we evaluated the activities of some
      enzymes of Krebs cycle, mitochondrial respiratory chain complexes and creatine
      kinase in the brain of young rats submitted to acute and chronic administration
      of fenproporex. In the acute administration, the animals received a single
      injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or tween. In the chronic
      administration, the animals received a single injection daily for 14 days of
      fenproporex (6.25, 12.5 or 25 mg/Kg i.p.). Two hours after the last injection,
      the rats were sacrificed by decapitation and the brain was removed for evaluation
      of biochemical parameters. Our results showed that the activities of citrate
      synthase, malate dehydrogenase and succinate dehydrogenase were increased by
      acute and chronic administration of fenproporex. Complexes I, II, II-III and IV
      and creatine kinase activities were also increased after acute and chronic
      administration of the drug. Our results are consistent with others reports that
      showed that some psychostimulant drugs increased brain energy metabolism in young
      rats.

PMID- 21723936
TI  - Activity of dlx5a/dlx6a regulatory elements during zebrafish GABAergic neuron
      development.
AB  - During vertebrate forebrain formation, Dlx homeobox genes play essential roles in
      the differentiation, migration and survival of subpallial precursor cells that
      will later give rise to diverse subtypes of gamma-aminobutyric acid (GABA)
      expressing neurons, including inhibitory cortical interneurons in mammals. They
      also participate in the regulation of the Gad genes encoding the enzymes
      necessary for GABA synthesis. In mice, at least four cis-regulatory elements
      (CREs) control Dlx expression in the telencephalon and diencephalon: URE2 and
      I12b in the Dlx1/Dlx2 bigene cluster, and I56i and I56ii in the Dlx5/Dlx6 bigene
      cluster. However, little is known so far with respect to the function of
      orthologous dlx genes and their regulatory elements during zebrafish GABAergic
      neuron development. To investigate whether similar dlx-mediated pathways exist in
      the early developing zebrafish forebrain, we generated independent lines of
      transgenic zebrafish carrying two distinct GFP reporter constructs driven by a
      beta-globin minimal promoter: one containing a ~1.4kb dlx5a/dlx6a intergenic
      sequence (encompassing I56i and I56ii) and one with a ~1.1kb fragment containing
      only the I56i CRE, respectively. The expression patterns of these two transgenes
      were compared with that obtained with another construct containing the ~1.4kb
      dlx5a/dlx6a intergenic sequence and driven by a ~3.5kb dlx6a 5'-flanking
      fragment. Our comparative analysis showed that GFP expression of the three
      transgene is largely overlapping throughout the ventral forebrain. Intriguingly,
      the dlx6a 5'-flanking fragment has a major impact on transgene expression in the
      mesencephalic tectum. Furthermore, comparison of transgene expression between the
      ~1.4kb and ~1.1kb intergenic fragments did not show any specific spatial
      expression conferred by I56ii. Almost all GFP-expressing cells in the transgenic
      zebrafish are GABA-positive and also express various GABAergic interneuron
      markers. Together, our data suggest that zebrafish dlx5a/dlx6a intergenic CREs
      may be involved in a conserved genetic pathway necessary for proper dlx
      expression during zebrafish GABAergic neuron development.

PMID- 21723937
TI  - Toxicity of fatty acids on ECV-304 endothelial cells.
AB  - The effects of stearic (saturated) or oleic (monounsaturated) acids and their
      combination with omega-3 and omega-6 polyunsaturated fatty acids (PUFA) on death
      of endothelial cells (ECV-304 cell line) were investigated. We examined: loss of
      plasma membrane integrity, DNA fragmentation, accumulation of neutral lipids (NL)
      and release of reactive oxygen species (ROS). The fatty acids studied were:
      stearic (SA), oleic (OA), docosahexaenoic (DHA), eicosapentaenoic (EPA), linoleic
      (LA) and gamma-linolenic (gammaA) acids. SA at 150 MUM induced cell death, did
      not lead to accumulation of NL and raised the release of ROS. omega-3 PUFA
      decreased ROS production, increased NL content but did not protect against ECV
      304 cell death induced by SA. omega-6 PUFA inhibited SA-induced cell death,
      increased NL content and decreased ROS production. OA caused cell death but did
      not increase NL content and ROS production even at 300 MUM. omega-3 and omega-6
      FA associated with OA further increased cell death with no change in ROS
      production and NL content. Concluding, omega-6 PUFA had a greater protective
      effect than omega-3 PUFA on the deleterious effects caused by SA whereas OA had
      low cytotoxicity but, when associated with PUFA, presented marked toxic effects
      on ECV-304 endothelial cells.

PMID- 21723938
TI  - Cytotoxicity and mitochondrial damage caused by silica nanoparticles.
AB  - Amorphous silica nanoparticles are widely applied in many fields. But the adverse
      effects of silica nanoparticle exposure were unclear. The present study
      investigated the cytotoxicity and mitochondrial damage of silica nanoparticles
      exposure in hepatocellular carcinoma cell line (HepG2). The cells were treated
      with 43 nm non-modified amorphous silica nanoparticles which dispersed in serum
      free DMEM at concentrations of 0, 25, 50, 100 and 200 MUg/mL for 3 and 24 h. The
      results showed that the silica nanoparticles could lead to increasing cellular
      reactive oxygen species (ROS) production for 3 and 24 h exposure. Moreover, the
      oxidative stress induced by the particles could play an important role of the
      mitochondrial membrane damage and the cell apoptosis. It indicated that apoptosis
      through mitochondrial pathway mediated by oxidative stress was a potential
      mechanism of cytotoxicity induced by silica nanoparticles. The particles could
      enter the cells through different pathways and dispersed in cytoplasm and
      deposited inside mitochondria. Mitochondria were the major organelles for the
      cytotoxicity of silica nanoparticles exposure. Mitochondrial damage was related
      to the oxidative stress and the direct injurious effect of nanoparticles. It can
      be considered as the potential mechanism for the cytotoxic effects of amorphous
      silica nanoparticles.

PMID- 21723939
TI  - The MAO inhibitor phenelzine improves functional outcomes in mice with
      experimental autoimmune encephalomyelitis (EAE).
AB  - Multiple sclerosis (MS) and the animal model, experimental autoimmune
      encephalomyelitis (EAE), are both accompanied by motor and non-motor symptoms.
      Pathological changes in the activities of key neurotransmitters likely underlie
      many of these symptoms. We have previously described disturbances in the levels
      of 5-hydroxytryptamine (5-HT/serotonin), noradrenaline (NE) and gamma
      aminobutyric acid (GABA) in a mouse model of EAE. The potential therapeutic
      effect of a drug that targets these three neurotransmitters, the antidepressant
      and anti-panic drug phenelzine (PLZ), was assessed in mice with MOG(35-55)
      induced EAE. The neurotransmitter content of EAE and control tissue after PLZ
      administration was first evaluated by HPLC. The ability of PLZ treatment to
      modulate EAE disease course and clinical signs was then assessed. Daily PLZ
      treatment, starting seven days after disease induction, delayed EAE onset,
      reduced disease severity in the chronic phase and was associated with substantial
      improvements in exploratory behavior and a novel measure of sickness and/or
      depression. Upon completion of the experiment, PLZ's effects on histopathological
      markers of the disease were examined. No differences were observed in T cell
      infiltration, microglia/macrophage reactivity, demyelination or axonal injury in
      PLZ-treated spinal cords. However, EAE mice treated with PLZ showed a
      normalization of 5-HT levels in the ventral horn of the spinal cord that might
      account for the improvements in behavioral outcomes. These results demonstrate
      the therapeutic potential of MAO inhibitors such as PLZ in MS. Additionally, the
      behavioral changes observed in EAE mice indicate that alterations in non-motor or
      'affective' measures may be valuable to consider in addition to traditional
      measures of gross locomotor function.

PMID- 21723940
TI  - Nurr1 is not essential for the development of prepulse inhibition deficits
      induced by prenatal immune activation.
AB  - Inflammation-induced disruption of fetal neurodevelopmental processes has been
      linked to the precipitation of long-lasting behavioral abnormalities and
      associated neuropathology. Recent longitudinal investigations in prenatal immune
      activation models have revealed developmental correspondences between the
      ontogeny of specific dopaminergic neuropathology and the postnatal onset of
      distinct forms of dopamine-dependent functional abnormalities implicated in
      schizophrenia. Two examples of such developmental correspondences are increased
      expression of the orphan nuclear receptor Nurr1 (NR4A2) in ventral midbrain areas
      and disruption of prepulse inhibition of the acoustic startle reflex, with both
      the neuroanatomical and behavioral effects emerging only in adult but not pre
      pubertal subjects exposed to prenatal maternal inflammation. In the present
      study, we tested the hypothesis that Nurr1 may be a critical molecular mediator
      of prepulse inhibition deficits induced by prenatal immune activation. To this
      end, we compared the effects of prenatal immune challenge on adult PPI in wild
      type (wt) mice and mice with a heterozygous constitutive deletion of Nurr1
      (Nurr1+/-) using a well established mouse model of maternal immune activation by
      exposure to the viral mimetic poly(I:C) (=polyriboinosinic-polyribocytidilic
      acid). We found that prenatal poly(I:C) treatment on gestation day 9 was
      similarly effective in disrupting prepulse inhibition in adult wt and Nurr1+/-
      mice. Prenatal poly(I:C) treatment also generally increased midbrain Nurr1
      positive cells and counteracted the genetically driven Nurr1 deficit in the
      substantia nigra. Our data thus suggest that at least under the present
      experimental conditions, Nurr1 is not essential for the development of prepulse
      inhibition deficits induced by prenatal immune activation.

PMID- 21723941
TI  - Tocotrienols inhibit AKT and ERK activation and suppress pancreatic cancer cell
      proliferation by suppressing the ErbB2 pathway.
AB  - Tocotrienols are members of the vitamin E family but, unlike tocopherols, possess
      an unsaturated isoprenoid side chain that confers superior anti-cancer
      properties. The ability of tocotrienols to selectively inhibit the HMG-CoA
      reductase pathway through posttranslational degradation and to suppress the
      activity of transcription factor NF-kappaB could be the basis for some of these
      properties. Our studies indicate that gamma- and delta-tocotrienols have potent
      antiproliferative activity in pancreatic cancer cells (Panc-28, MIA PaCa-2, Panc
      1, and BxPC-3). Indeed both tocotrienols induced cell death (>50%) by the MTT
      cell viability assay in all four pancreatic cancer cell lines. We also examined
      the effects of the tocotrienols on the AKT and the Ras/Raf/MEK/ERK signaling
      pathways by Western blotting analysis. gamma- and delta-tocotrienol treatment of
      cells reduced the activation of ERK MAP kinase and that of its downstream
      mediator RSK (ribosomal protein S6 kinase) in addition to suppressing the
      activation of protein kinase AKT. Suppression of activation of AKT by gamma
      tocotrienol led to downregulation of p-GSK-3beta and upregulation accompanied by
      nuclear translocation of Foxo3. These effects were mediated by the downregulation
      of Her2/ErbB2 at the messenger level. Tocotrienols but not tocopherols were able
      to induce the observed effects. Our results suggest that the tocotrienol isoforms
      of vitamin E can induce apoptosis in pancreatic cancer cells through the
      suppression of vital cell survival and proliferative signaling pathways such as
      those mediated by the PI3-kinase/AKT and ERK/MAP kinases via downregulation of
      Her2/ErbB2 expression. The molecular components for this mechanism are not
      completely elucidated and need further investigation.

PMID- 21723942
TI  - Cyclic AMP signalling through PKA but not Epac is essential for neurturin-induced
      biphasic ERK1/2 activation and neurite outgrowths through GFRalpha2 isoforms.
AB  - Cyclic AMP (cAMP) and neurotrophic factors are known to interact closely to
      promote neurite outgrowth and neuronal regeneration. Glial cell line-derived
      neurotrophic factor (GDNF) and its family member neurturin (NTN) transduce signal
      through a multi-component receptor complex consisting of GDNF family receptor
      alpha 2 (GFRalpha2) and Ret receptor tyrosine kinase. Neurons from GFRalpha2
      deficient mice do not promote axonal initiation when stimulated by NTN,
      consistent with the role of GFRalpha2 in neuronal outgrowth. Multiple
      alternatively spliced isoforms of GFRalpha2 are known to be expressed in the
      nervous system. GFRalpha2a and GFRalpha2c but not GFRalpha2b promoted neurite
      outgrowth. It is currently unknown if cAMP signalling is differentially regulated
      by these isoforms. In this study, NTN activation of GFRalpha2a and GFRalpha2c but
      not GFRalpha2b induced biphasic ERK1/2 activation and phosphorylation of the
      major cAMP target CREB. Interestingly, inhibition of cAMP signalling
      significantly impaired GFRalpha2a and GFRalpha2c-mediated neurite outgrowth while
      cAMP agonists cooperated with GFRalpha2b to induce neurite outgrowth.
      Importantly, the specific cAMP effector PKA but not Epac was essential for NTN
      induced neurite outgrowth, through transcription and translation-dependent
      activation of late phase ERK1/2. Taken together, these results not only
      demonstrated the essential role of cAMP-PKA signalling in NTN-induced biphasic
      ERK1/2 activation and neurite outgrowth, but also suggested cAMP-PKA signalling
      as a hitherto unrecognized underlying mechanism contributing to the differential
      neuritogenic activities of GFRalpha2 isoforms.

PMID- 21723943
TI  - Dependence on different Rab GTPases for the trafficking of CXCR4 and CCR5 homo or
      heterodimers between the endoplasmic reticulum and plasma membrane in Jurkat
      cells.
AB  - Much is known about G protein coupled receptor trafficking and internalization
      following agonist stimulation. However, much less is known about outward
      trafficking of receptors from synthesis in the endoplasmic reticulum to the
      plasma membrane, or the role that trafficking might play in the assembly of
      receptor signaling complexes, important for targeting, specificity, and rapidity
      of subsequent signaling events. Up to now, very little is understood about
      receptor hetero-oligomers other than the fact that their assembly is done rapidly
      after biosynthesis. In our study we use bimolecular fluorescence complementation
      to selectively follow receptor dimers when expressed in Jurkat cells in order to
      clarify the trafficking itinerary those receptors follow to reach the plasma
      membrane and the resulting effect on signal transduction. CXCR4 and CCR5,
      previously shown to form both homo and hetero-oligomers, were used as our model
      to understand the specificities of trafficking along the anterograde pathway. The
      CXCR4 homodimer relies on Rabs2, 6 and 8 for anterograde transport regardless of
      the presence of endogenous CD4. The CCR5 homodimer relies on Rabs1 and 11 when
      CD4 is absent, but Rabs1 and 8 when CD4 was present. Interestingly, similar to
      the CCR5 homodimer, the CXCR4-CCR5 heterodimer relied on Rabs1 and 11 but also
      required Rab2 when CD4 was absent, and only Rab 1 when CD4 was present. Our
      results demonstrate that, although the receptors composing the heterodimeric
      complex are the same as in the homodimeric ones, the heterodimer traffics and
      signals differently than each homodimer. Our study demonstrates the importance of
      considering the receptor heterodimers as distinct signaling entities that should
      be carefully and individually characterized.

PMID- 21723944
TI  - Control of Cdc14 activity coordinates cell cycle and development in
      Caenorhabditis elegans.
AB  - Much of our understanding of the function and regulation of the Cdc14 family of
      dual-specificity phosphatases originates from studies in yeasts. In these
      unicellular organisms Cdc14 is an important regulator of M-phase events. In
      contrast, the Caenorhabditis elegans homolog, cdc-14, is not necessary for
      mitosis, rather it is crucial for G(1)/S regulation to establish developmental
      cell-cycle quiescence. Despite the importance of integrating cdc-14 regulation
      with development, the mechanisms by which this coordination occurs are largely
      unknown. Here, we demonstrate that several processes conspire to focus the
      activity of cdc-14. First, the cdc-14 locus can produce at least six protein
      variants through alternative splicing. We find that a single form, CDC-14C, is
      the key variant acting during vulva development. Second, CDC-14C expression is
      limited to a subset of cells, including vulva precursors, through post
      transcriptional regulation. Lastly, the CDC-14C subcellular location, and thus
      its potential interactions with other regulatory proteins, is regulated by
      nucleocytoplasmic shuttling. We find that the active export of CDC-14C from the
      nucleus during interphase is dependent on members of the Cyclin D and Crm1
      families. We propose that these mechanisms collaborate to restrict the activity
      of cdc-14 as central components of an evolutionarily conserved regulatory network
      to coordinate cell-cycle progression with development.

PMID- 21723945
TI  - Bioadhesive film formed from a novel organic-inorganic hybrid gel for transdermal
      drug delivery system.
AB  - A novel organic-inorganic hybrid film-forming agent for TDDS was developed by a
      modified poly(vinyl alcohol) (PVA) gel using gamma
      (glycidyloxypropyl)trimethoxysilane (GPTMS) as an inorganic-modifying agent,
      poly(N-vinyl pyrrolidone) (PVP) as a tackifier and glycerol (GLY) as a
      plasticizer. The prepared gels can be applied to the skin by a coating method and
      in situ form very thin and transparent films with good performance, comfortable
      feel and cosmetic attractiveness. The key properties of the bioadhesive films
      produced from the hybrid gels were investigated and the results showed that the
      incorporation of appropriate GPTMS (GPTMS/(PVA+GPTMS) in the range of 20-30%)
      into the PVA matrix not only can significantly enhance mechanical strength and
      skin adhesion properties of the resultant film, but also can decrease the
      crystalline regions of PVA and hence facilitate the diffusion of water vapor and
      drug. Furthermore, the investigations into in vivo skin irritation suggested the
      films caused non-irritation to skin after topical application for 120 h. In
      conclusion, the bioadhesive films formed from organic-inorganic hybrid gels
      possessed very good qualities for application on the skin and may provide a
      promising formulation for TDDS, especially when the patient acceptability from an
      aesthetic perspective of the dosage form is a prime consideration.

PMID- 21723946
TI  - Retinoid-related orphan receptor alpha and the regulation of lipid homeostasis.
AB  - Many nuclear hormone receptors (NRs) control lipid, glucose and energy
      homeostasis in an organ specific manner. Concordantly, dysfunctional NR
      signalling results in metabolic disease. The Retinoic acid receptor-related
      orphan receptor alpha (RORalpha), a member of the NR1F subgroup, is expressed in
      metabolic tissues. Previous studies identified the role of this NR in
      dyslipidemia, apo-lipoprotein metabolism and atherosclerosis. Recent data is
      underscoring the significant role of this orphan NR in the regulation of phase
      I/II metabolism (bile acids, xenobiotics, steroids etc.), adiposity, insulin
      signalling, and glucose tolerance. Moreover, oxygenated sterols, have been
      demonstrated to function as native ligands and inverse agonists. This review
      focuses on the rapidly emerging and evolving role of RORalpha in the control of
      lipid and glucose homeostasis in major mass metabolic tissues. Article from the
      special issue orphan receptors.

PMID- 21723947
TI  - The road forward: the scientific basis for tetracycline treatment of arthritic
      disorders.
AB  - The potential role of a collagenase inhibitor for treatment of arthritis was
      recognized almost immediately after the discovery of vertebrate collagenase. Yet
      despite vast efforts from the pharmaceutical industry, no such drug has been
      approved for such use by a regulatory agency. Although two semisynthetic
      antimicrobial tetracyclines, viz. minocycline and doxycycline, have been shown to
      have modest clinical benefits in over a dozen trials in rheumatoid arthritis,
      neither drug is in widespread use. The almost universal use of methotrexate and
      the rapid development of potent biologic agents have eclipsed the potential usage
      of TETs for RA. Ironically, it is in osteoarthritis, where there has only been
      one clinical trial which essentially failed, that the best potential exists for
      use of an MMP-inhibiting TET.

PMID- 21723948
TI  - Characterization of groups using composite kernels and multi-source fMRI analysis
      data: application to schizophrenia.
AB  - Pattern classification of brain imaging data can enable the automatic detection
      of differences in cognitive processes of specific groups of interest.
      Furthermore, it can also give neuroanatomical information related to the regions
      of the brain that are most relevant to detect these differences by means of
      feature selection procedures, which are also well-suited to deal with the high
      dimensionality of brain imaging data. This work proposes the application of
      recursive feature elimination using a machine learning algorithm based on
      composite kernels to the classification of healthy controls and patients with
      schizophrenia. This framework, which evaluates nonlinear relationships between
      voxels, analyzes whole-brain fMRI data from an auditory task experiment that is
      segmented into anatomical regions and recursively eliminates the uninformative
      ones based on their relevance estimates, thus yielding the set of most
      discriminative brain areas for group classification. The collected data was
      processed using two analysis methods: the general linear model (GLM) and
      independent component analysis (ICA). GLM spatial maps as well as ICA temporal
      lobe and default mode component maps were then input to the classifier. A mean
      classification accuracy of up to 95% estimated with a leave-two-out cross
      validation procedure was achieved by doing multi-source data classification. In
      addition, it is shown that the classification accuracy rate obtained by using
      multi-source data surpasses that reached by using single-source data, hence
      showing that this algorithm takes advantage of the complimentary nature of GLM
      and ICA.

PMID- 21723949
TI  - Ketamine effects on brain function--simultaneous fMRI/EEG during a visual oddball
      task.
AB  - BACKGROUND: Behavioral and electrophysiological human ketamine models of
      schizophrenia are used for testing compounds that target the glutamatergic
      system. However, corresponding functional neuroimaging models are difficult to
      reconcile with functional imaging and electrophysiological findings in
      schizophrenia. Resolving the discrepancies between different observational levels
      is critical to understand the complex pharmacological ketamine action and its
      usefulness for modeling schizophrenia pathophysiology. METHODS: We conducted a
      within-subject, randomized, placebo-controlled pharmacoimaging study in twenty
      four male volunteers. Subjects were given low-dose S-ketamine (bolus prior to
      functional imaging: 0.1mg/kg during 5min, thereafter continuous infusion:
      0.015625mg/kg/min reduced by 10% every ten minutes) or placebo while performing a
      visual oddball task during simultaneous functional magnetic resonance imaging
      (fMRI) with continuous recording of event-related potentials (P300) and
      electrodermal activity (EDA). Before and after intervention, psychopathological
      status was assessed using the Positive and Negative Syndrome Scale (PANSS) and
      the Altered State of Consciousness (5D-ASC) Rating Scale. RESULTS: P300 amplitude
      and corresponding BOLD responses were diminished in the ketamine condition in
      cortical regions being involved in sensory processing/selective attention. In
      both measurement modalities separation of drug conditions was achieved with area
      under the curve (AUC) values of up to 0.8-0.9. Ketamine effects were also
      observed in the clinical, behavioral and peripheral physiological domains
      (Positive and Negative Syndrome Scale, reaction hit and false alarm rate,
      electrodermal activity and heart rate) which were in part related to the
      P300/fMRI measures. CONCLUSION: The findings from our ketamine experiment are
      consistent across modalities and directly related to observations in
      schizophrenia supporting the validity of the model. Our investigation provides
      the first prototypic example of a pharmacoimaging study using simultaneously
      acquired fMRI/EEG.

PMID- 21723950
TI  - Patient classification as an outlier detection problem: an application of the One
      Class Support Vector Machine.
AB  - Pattern recognition approaches, such as the Support Vector Machine (SVM), have
      been successfully used to classify groups of individuals based on their patterns
      of brain activity or structure. However these approaches focus on finding group
      differences and are not applicable to situations where one is interested in
      accessing deviations from a specific class or population. In the present work we
      propose an application of the one-class SVM (OC-SVM) to investigate if patterns
      of fMRI response to sad facial expressions in depressed patients would be
      classified as outliers in relation to patterns of healthy control subjects. We
      defined features based on whole brain voxels and anatomical regions. In both
      cases we found a significant correlation between the OC-SVM predictions and the
      patients' Hamilton Rating Scale for Depression (HRSD), i.e. the more depressed
      the patients were the more of an outlier they were. In addition the OC-SVM split
      the patient groups into two subgroups whose membership was associated with future
      response to treatment. When applied to region-based features the OC-SVM
      classified 52% of patients as outliers. However among the patients classified as
      outliers 70% did not respond to treatment and among those classified as non
      outliers 89% responded to treatment. In addition 89% of the healthy controls were
      classified as non-outliers.

PMID- 21723951
TI  - The evolution of mitochondrial genomes in subterranean caviomorph rodents:
      adaptation against a background of purifying selection.
AB  - South American tuco-tucos (Ctenomys) and the related coruro (Spalacopus) are two
      rodent lineages that have independently colonised the subterranean niche. The
      energetically demanding lifestyles of these species, coupled with the hypoxic
      atmospheres characteristic of subterranean environments, may have altered the
      selective regimes on genes encoding proteins related to cellular respiration.
      Here, we examined the molecular evolution of 13 protein-coding genes in the
      mitochondrial genome of seven caviomorph rodents, including these two
      subterranean genera and their above-ground relatives. Using maximum-likelihood
      and Bayesian approaches, we estimated rates of synonymous (dS) and nonsynonymous
      (dN) substitutions. We found a significantly higher omega ratio (dN/dS) in
      subterranean groups as compared to their non-subterranean counterparts in 11 of
      13 genes, although no omega ratio was larger than 1. Additionally, we applied a
      method based on quantitative physicochemical properties to test for positive
      selection. Amino acid changes implicated in radical structural or functional
      shifts in the protein property were found to be ubiquitous across the phylogeny,
      but concentrated in the subterranean lineages. Convergent changes were also found
      between the subterranean genera used in this study and other mammals adapted to
      hypoxia. The results of this study suggest a link between niche shifts and weak
      directional (or episodic) selection at the molecular level against a background
      of purifying selection.

PMID- 21723952
TI  - Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a
      naturally occurring model of disease.
AB  - OBJECTIVE: To examine effects of high omega-3 (n-3) polyunsaturated fatty acid
      (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig
      model, and to further characterise pathogenesis in this model. Modern diets low
      in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly
      including OA. However, n-3 is also thought to increases bone density, which is a
      possible contributing factor in OA. Therefore we aim to determine the net
      influence of n-3 in disease development. METHOD: OA-prone Dunkin-Hartley (DH)
      Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a
      standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and
      subchondral bone pathology by histology, and biochemistry, including collagen
      cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase,
      glycosaminoglycan (GAG), and denatured type II collagen. RESULTS: Dietary n-3
      reduced disease in OA-prone animals. Most cartilage parameters were modified by n
      3 diet towards those seen in the non-pathological BS2 strain - significantly
      active MMP-2, lysyl-pyridinoline and total collagen cross-links - the only
      exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG
      content was higher and denatured type II lower in the n-3 group. Subchondral bone
      parameters in the DH n-3 group also changed towards those seen in the non
      pathological strain, significantly calcium:phosphate ratios and epiphyseal bone
      density. CONCLUSION: Dietary n-3 PUFA reduced OA in the prone strain, and most
      disease markers were modified towards those of the non-OA strain, though not all
      significantly so. Omega-3 did not increase markers of pathology in either strain.

PMID- 21723953
TI  - Pain and analgesia: The dual effect of nitric oxide in the nociceptive system.
AB  - Nitric oxide (NO) is involved in many physiological processes and several lines
      of evidence have indicated that NO plays a complex and diverse role in the
      modulation of pain. Nitric oxide is an important neurotransmitter involved in the
      nociceptive process and, in the dorsal horn of the spinal cord, it contributes to
      the development of central sensitization. On the other hand, experimental data
      have also demonstrated that NO inhibits nociception in the peripheral and also in
      the central nervous system. In addition, it has been shown that nitric oxide
      mediates the analgesic effect of opioids and other analgesic substances. The
      information included in the present review aims to present and analyze data about
      the dual effect of NO on pain transmission and control, the molecular mechanisms
      involved in these effects and also the potential use of nitric oxide in pain
      therapy.

PMID- 21723954
TI  - The role of thromboxane A(2) in the pathogenesis of intrauterine growth
      restriction associated with maternal smoking in pregnancy.
AB  - BACKGROUND: To examine the effect of maternal smoking in pregnancy on the
      production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their
      role in the pathogenesis of intrauterine growth restriction. METHODS: Prospective
      case control study enrolled smoking and non-smoking women at <=14 weeks
      gestation. Maternal urine samples were obtained at <=14, 28 and 36 weeks. High
      performance liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to
      quantify 11-dehydrothromboxane B(2) (TX-M) and 2,3 dinor-6-ketoprostaglandin
      F1alpha (PG-M), stable urinary metabolites of thromboxane A(2) and prostacyclin
      I2. Confirmation of the smoking status was performed by quantitation of urinary
      nicotine metabolites. Data was analysed using SPSS and Stata((r)). RESULTS:
      Thirty five were enrolled in the smoking group and 32 in the non-smoking group.
      Smoking resulted higher levels of TX-M at <=14, 28 and 36 weeks gestation. There
      was no difference in PG-M at any gestational time point between the two groups.
      The median customised birthweight centile in the smoking group was 17.0 (0-78)
      compared to 55.5 (4-100) in the non-smoking group (P<0.001). A causal
      relationship between elevated TX-M and IUGR could not be established.
      CONCLUSIONS: Maternal smoking in pregnancy is associated with altered eicosanoid
      production in favour of the vasoconstrictor thromboxane A(2) which occurs early
      in the first trimester.

PMID- 21723955
TI  - Animal models of asthma: value, limitations and opportunities for alternative
      approaches.
AB  - Asthma remains an area of considerable unmet medical need. Few new drugs have
      made it to the clinic during the past 50 years, with many that perform well in
      preclinical animal models of asthma, failing in humans owing to lack of safety
      and efficacy. The failure to translate promising drug candidates from animal
      models to humans has led to questions about the utility of in vivo studies and to
      demand for more predictive models and tools based on the latest technologies.
      Following a workshop with experts from academia and the pharmaceutical industry,
      we suggest here a disease modelling framework designed to better understand human
      asthma, and accelerate the development of safe and efficacious new asthma drugs
      that go beyond symptomatic relief.

PMID- 21723956
TI  - Evaluation of the genotoxicity of Crotalus durissus terrificus snake venom and
      its isolated toxins on human lymphocytes.
AB  - In the present study, experiments were carried out to evaluate the mutagenic
      potential and genotoxic effects of Crotalus durissus terrificus snake venom and
      its isolated toxins on human lymphocytes, using the micronucleus and comet
      assays. Significant damage to DNA was observed for crotoxin and crotapotin (CA).
      Basic phospholipase A(2) (CB) and crotamine did not present any mutagenic
      potential when evaluated by the micronucleus test. C. d. terrificus crude venom
      was able to induce the formation of micronuclei, similarly to the mutagenic drug
      used as a positive control. In the comet assay, all the toxins tested (crotamine,
      crotoxin, CB and CA) and C. d. terrificus venom presented genotoxic activity.
      Studies on the cytogenetic toxicology of animal venoms and their isolated
      proteins are still very scarce in the literature, which emphasizes the importance
      of the present work for the identification and characterization of potential
      therapeutic agents, as well as for the better understanding of the mechanisms of
      action of toxins on the human body.

PMID- 21723957
TI  - Leishmanicidal activity of the Agaricus blazei Murill in different Leishmania
      species.
AB  - Leishmaniasis is a major public health problem, and the alarming spread of
      parasite resistance underlines the importance of discovering new therapeutic
      products. The present study aims to investigate the in vitro leishmanicidal
      activity of an Agaricus blazei Murill mushroom extract as compared to different
      Leishmania species and stages. The water extract proved to be effective against
      promastigote and amastigote-like stages of Leishmania amazonensis, L. chagasi,
      and L. major, with IC(50) (50% inhibitory concentration) values of 67.5, 65.8,
      and 56.8 MUg/mL for promastigotes, and 115.4, 112.3, and 108.4 MUg/mL for
      amastigotes-like respectively. The infectivity of the three Leishmania species
      before and after treatment with the water extract was analyzed, and it could be
      observed that 82%, 57%, and 73% of the macrophages were infected with L.
      amazonensis, L. major, and L. chagasi, respectively. However, when parasites were
      pre-incubated with the water extract, and later used to infect macrophages, they
      were able to infect only 12.7%, 24.5%, and 19.7% of the phagocytic cells for L.
      amazonensis, L. chagasi, and L. major, respectively. In other experiments,
      macrophages were infected with L. amazonensis, L. chagasi, or L. major, and later
      treated with the aforementioned extract, presented reductions of 84.4%, 79.6%,
      and 85.3% in the parasite burden after treatment. A confocal microscopy revealed
      the loss of the viability of the parasites within the infected macrophages after
      treatment with the water extract. The applied extract presented a low
      cytotoxicity in murine macrophages and a null hemolytic activity in type O(+)
      human red blood cells. No nitric oxide (NO) production, nor inducible nitric
      oxide syntase expression, could be observed in macrophages after stimulation with
      the water extract, suggesting that biological activity may be due to direct
      mechanisms other than macrophage activation by means of NO production. In
      conclusion, the results demonstrate that the A. blazei Murill water extract can
      potentially be used as a therapeutic alternative on its own, or in association
      with other drugs, to treat Visceral and Cutaneous Leishmaniasis.

PMID- 21723958
TI  - Development of real-time PCR assay for differential detection and quantification
      for multiple Babesia microti-genotypes.
AB  - We have developed a real-time PCR assay that can rapidly and differentially
      detect and quantify four genotypes of small subunit ribosomal RNA gene (SSUrDNA)
      of Babesia microti (Kobe-, Otsu-, Nagano- and US-types). In this assay, four
      genotype-specific pairs of primers targeted on internal transcribed spacer (ITS)
      1 or 2 sequences were used and amplicons by each pair of primers were
      quantitatively detected by fluorescent SYBR Green I. The four genotype-specific
      pairs of primers displayed the high specificity for homologous genotype DNA. The
      standard curves of cycle threshold (Ct) values versus amount of target DNA per
      reaction (log) for all four genotypes were linear and the correlation coefficient
      (Rsq) values for the curves were from 0.970 to 0.997. The standard curves were
      almost identical even in the presence of heterologous genotype DNA. This assay
      could detect 10-30 fg purified DNA (equivalent to the amount of 1-5 parasite DNA)
      of each genotype B. microti. This assay could also detect each genotype B.
      microti infection in blood with 3*10(-6)%-1*10(-5)% parasitemia. This assay was
      applicable to field rodent and tick samples to reveal mixed infection in several
      samples, for which a single genotype of B. microti had been detected by direct
      sequencing analyses in our previous studies. This assay also seemed to be
      applicable to clinical human samples, showing Kobe-type positive results for the
      first Japanese babesiosis patient and the asymptomatic donor, both infected with
      Kobe-type B. microti.

PMID- 21723959
TI  - Gyrodactylus longipes n. sp. (Monogenea: Gyrodactylidae) from farmed gilthead
      seabream (Sparus aurata L.) from the Mediterranean.
AB  - Gyrodactylus longipes n. sp. (Monogenea, Gyrodactylidae) is described from the
      gills of farmed juvenile gilthead seabream (Sparus aurata L.) from two sites
      located in Italy and Bosnia-Herzegovina and represents the second species of
      Gyrodactylus to be described from S. aurata. Gyrodactylus orecchiae Paladini,
      Cable, Fioravanti, Faria, Di Cave et Shinn, 2009 was the first gyrodactylid to be
      described from S. aurata, from populations cultured in Albania and Croatia. In
      the current study, G. longipes was found in a mixed infection with G. orecchiae
      on fish maintained in Latina Province, Italy, thus extending the reported
      distribution of the latter throughout the Mediterranean. The morphology of the
      opisthaptoral hard parts of G. longipes is compared to those of G. orecchiae,
      using light and scanning electron microscopy. Gyrodactylus longipes is
      characterised by having larger, elongated ventral bar processes and long,
      triangular-shaped toe region to their marginal hook sickles which, by comparison,
      are rhomboid in G. orecchiae. The marginal hook sickles of G. longipes are almost
      double the size of G. orecchiae which allows for their rapid discrimination from
      each other in mixed infections. A comparison of the DNA sequence of the ribosomal
      internal transcribed spacer 1 and 2 regions (ITS1 and ITS2) of G. longipes with
      the corresponding sequence from G. orecchiae and with those available in GenBank,
      supports the separate species status of G. longipes. Part of this study
      necessitated an overview of the existing Gyrodactylus fauna from Italy and Bosnia
      Herzegovina; a summary from each country is provided here to assist future
      investigations.

PMID- 21723960
TI  - Enhancing phylogeography by improving geographical information from GenBank.
AB  - Phylogeography is a field that focuses on the geographical lineages of species
      such as vertebrates or viruses. Here, geographical data, such as location of a
      species or viral host is as important as the sequence information extracted from
      the species. Together, this information can help illustrate the migration of the
      species over time within a geographical area, the impact of geography over the
      evolutionary history, or the expected population of the species within the area.
      Molecular sequence data from NCBI, specifically GenBank, provide an abundance of
      available sequence data for phylogeography. However, geographical data is
      inconsistently represented and sparse across GenBank entries. This can impede
      analysis and in situations where the geographical information is inferred, and
      potentially lead to erroneous results. In this paper, we describe the current
      state of geographical data in GenBank, and illustrate how automated processing
      techniques such as named entity recognition, can enhance the geographical data
      available for phylogeographic studies.

PMID- 21723961
TI  - Protective action of endogenously generated H2S on hypoxia-induced respiratory
      suppression and its relation to antioxidation and down-regulation of c-fos mRNA
      in medullary slices of neonatal rats.
AB  - We previously reported that exogenous H(2)S played roles in protection of
      respiratory centers against hypoxic injury in medullary slices of neonatal rats.
      The protective action of endogenous H(2)S and its relation to antioxidation and
      down-regulation of c-fos mRNA were investigated in the present study. Perfusion
      of the slices with l-cysteine (Cys), substrate of cystathionine beta-synthase
      (CBS, H(2)S synthase), could increase frequency of rhythmic respiratory discharge
      of the hypoglossal rootlets and prevent respiratory suppression induced by
      hypoxia, whereas perfusion with hydroxylamine (NH(2)OH, inhibitor of CBS) could
      postpone recovery of respiration from hypoxic inhibition. NH(2)OH also
      significantly enhanced hypoxia-induced increase in malondialdehyde (MDA) content
      of the slices. The hypoxia-induced up-regulation of c-fos mRNA could be markedly
      antagonized by S-adenosyl-l-methionine (SAM, activator of CBS), but greatly
      increased by NH(2)OH. Neither NH(2)OH, Cys nor SAM had any effect on expression
      of bcl-2 mRNA in hypoxic medullary slices. These results indicate that
      endogenously generated H(2)S was involved in protection of the medullary
      respiratory centers against hypoxic injury partly via antioxidation and down
      regulation of c-fos.

PMID- 21723962
TI  - Biomimetic bone-like composites fabricated through an automated alternate soaking
      process.
AB  - Hydroxyapatite-gelatin composites have been proposed as suitable scaffolds for
      bone and dentin tissue regeneration. There is considerable interest in producing
      these scaffolds using biomimetic methods due to their low energy costs and
      potential to create composites similar to the tissues they are intended to
      replace. Here an existing process used to coat a surface with hydroxyapatite
      under near physiological conditions, the alternate soaking process, is modified
      and automated using an inexpensive "off the shelf" robotics kit. The process is
      initially used to precipitate calcium phosphate coatings. Then, in contrast to
      previous utilizations of the alternate soaking process, gelatin was added
      directly to the solutions in order to co-precipitate hydroxyapatite-gelatin
      composites. Samples were investigated by Fourier transform infrared spectroscopy,
      scanning electron microscopy, energy dispersive X-ray spectroscopy and
      nanoindentation. Calcium phosphate coatings formed by the alternate soaking
      process exhibited different calcium to phosphate ratios, with correspondingly
      distinct structural morphologies. The coatings demonstrated an interconnected
      structure with measurable mechanical properties, even though they were 95%
      porous. In contrast, hydroxyapatite-gelatin composite coatings over 2mm thick
      could be formed with little visible porosity. The hydroxyapatite-gelatin
      composites demonstrate a composition and mechanical properties similar to those
      of cortical bone.

PMID- 21723963
TI  - Assessment of angiogenesis in osseointegration of a silica-collagen biomaterial
      using 3D-nano-CT.
AB  - Bony integration of biomaterials is a complex process in which angiogenesis plays
      a crucial role. We evaluated micro- and nano-CT imaging to demonstrate and
      quantify neovascularization in bony integration of a biomaterial and to give an
      image based estimation for the needed resolution for imaging angiogenesis in an
      animal model of femora defect healing. In 8 rats 5mm full-size defects were
      created at the left femur that was filled with silica-collagen bone substitute
      material and internally fixed with plate osteosynthesis. After 6 weeks the femora
      were infused in situ with Microfil, harvested and scanned for micro-CT (9 MUm)(3)
      and nano-CT (3 MUm)(3) imaging. Using those 3D images, the newly formed blood
      vessels in the area of the biomaterial were assessed and the total vascular
      volume fraction, the volume of the bone substitute material and the volume of the
      bone defect were quantitatively characterized. Results were complemented by
      histology. Differences were statistically assessed using (ANOVA). High-resolution
      nano-CT demonstrated new blood vessel formation surrounding the biomaterial in
      all animals at capillary level. Immunohistochemistry confirmed the newly formed
      blood vessels surrounding the bone substitute material. The mean vascular volume
      fraction (VVF) around the implant was calculated to be 3.01 +/- 0.4%. The VVF was
      inversely correlated with the volume of the bone substitute material (r=0.8) but
      not with the dimension of the fracture zone (r=0.3). Nano-CT imaging is feasible
      for quantitative analysis of angiogenesis during bony integration of biomaterials
      and a promising tool in this context for the future.

PMID- 21723964
TI  - Effects of UV photofunctionalization on the nanotopography enhanced initial
      bioactivity of titanium.
AB  - This study addresses the control of the biological capabilities of titanium
      through specific nanosurface features and its potential modulation by UV
      photofunctionalization. Rat bone marrow derived osteoblasts were cultured on
      titanium disks with micropits alone, micropits with 100 nm nodules, micropits
      with 300 nm nodules, or micropits with 500 nm nodules, with or without UV
      treatment. After a 24 h incubation protein adsorption, as well as the attachment,
      retention, and spread of osteoblasts were examined in correlation with the
      topographical parameters of the titanium substrates. Each of the biological
      events was governed by a different set of multiple surface topographical factors
      with a distinctive pattern of regulation. For instance, without UV treatment the
      protein adsorption and cell attachment capability of titanium substrates
      increased linearly with increasing average roughness (Ra) and surface area of
      titanium disks, but increased polynomially with increasing nanonodule diameter.
      The cell retention capability increased polynomially with increasing nanonodular
      diameter and Ra, but increased linearly with increasing surface area.
      Consequently, the micropits with 300 nm nodules created the most favorable
      environment for this initial osteoblast behavior and response. UV treatment of
      the nanonodular titanium surfaces resulted in considerable enhancement of all
      biological events. However, the pattern of UV-mediated enhancement was
      disproportionate; exponential and overriding effects were observed depending upon
      the biological event and topographical parameter. As an example of overriding
      enhancement, the cell retention capability, which fluctuated with changes in
      various topographical parameters, became invariably high after UV treatment. The
      present data provide a basis for understanding how to optimize nanostructures to
      create titanium surfaces with increased biological capabilities and uncover a
      novel advantage of UV photofunctionalization of titanium substrates that
      synergistically increases its nanotopography enhanced biological capabilities
      whereby most of the initial biological events of osteoblasts were overwhelmingly
      enhanced beyond a simple proportional increase.

PMID- 21723965
TI  - Predicting the glass transition temperature of bioactive glasses from their
      molecular chemical composition.
AB  - A recently published paper (M.D. O'Donnell, Acta Biomaterialia 7 (2011) 2264
      2269) suggests that it is possible to correlate the glass transition temperature
      (T(g)) of bioactive glasses with their molar composition, based on iterative
      least-squares fitting of published T(g) data. However, we show that the glass
      structure is an important parameter in determining T(g). Phase separation, local
      structural effects and components (intermediate oxides) which can switch their
      structural role in the glass network need to be taken into consideration, as they
      are likely to influence the glass transition temperature of bioactive glasses.
      Although the model suggested by O'Donnell works reasonably well for glasses
      within the composition range presented, it is oversimplified and fails for
      glasses outside certain compositional boundaries.

PMID- 21723966
TI  - Designing optimal calcium phosphate scaffold-cell combinations using an
      integrative model-based approach.
AB  - Bone formation is a very complex physiological process, involving the
      participation of many different cell types and regulated by countless
      biochemical, physical and mechanical factors, including naturally occurring or
      synthetic biomaterials. For the latter, calcium phosphate (CaP)-based scaffolds
      have proven to stimulate bone formation, but at present still result in a wide
      range of in vivo outcomes, which is partly related to the suboptimal use and
      combination with osteogenic cells. To optimize CaP scaffold selection and make
      their use in combination with cells more clinically relevant, this study uses an
      integrative approach in which mathematical modeling is combined with experimental
      research. This paper describes the development and implementation of an
      experimentally informed bioregulatory model of the effect of calcium ions
      released from CaP-based biomaterials on the activity of osteogenic cells and
      mesenchymal stem cell driven ectopic bone formation. The amount of bone formation
      predicted by the mathematical model corresponds to the amount measured
      experimentally under similar conditions. Moreover, the model is also able to
      qualitatively predict the experimentally observed impaired bone formation under
      conditions such as insufficient cell seeding and scaffold decalcification. A
      strategy was designed in silico to overcome the negative influence of a low
      initial cell density on the bone formation process. Finally, the model was
      applied to design optimal combinations of calcium-based biomaterials and cell
      culture conditions with the aim of maximizing the amount of bone formation. This
      work illustrates the potential of mathematical models as research tools to design
      more efficient and cell-customized CaP scaffolds for bone tissue engineering
      applications.

PMID- 21723967
TI  - Comparative study of bovine, porcine and avian collagens for the production of a
      tissue engineered dermis.
AB  - Combining bovine collagen with chitosan followed by freeze-drying has been shown
      to produce porous scaffolds suitable for skin and connective tissue engineering
      applications. In this study collagen extracted from porcine and avian skin was
      compared with bovine collagen for the production of tissue engineered scaffolds.
      A similar purity of the collagen extracts was shown by electrophoresis,
      confirming the reliability of the extraction process. Collagen was solubilized,
      cross-linked by adding chitosan to the solution and freeze-dried to generate a
      porous structure suitable for tissue engineering applications. Scaffold porosity
      and pore morphology were shown to be source dependant, with bovine collagen and
      avian collagen resulting into the smallest and largest pores, respectively.
      Scaffolds were seeded with dermal fibroblasts and cultured for 35 days to
      evaluate the suitability of the different collagen-chitosan scaffolds for long
      term tissue engineered dermal substitute maturation in vitro. Cell proliferation
      and scaffold biocompatibility were found to be similar for all the collagen
      chitosan scaffolds, demonstrating their capability to support long-term cell
      adhesion and growth. The scaffolds contents was assessed by immunohistochemistry
      and showed increased deposition of extracellular matrix by the cells as a
      function of time. These results correlate with measurements of the mechanical
      properties of the scaffolds, since both the ultimate tensile strength and tensile
      modulus of the cell seeded scaffolds had increased by the end of the culture
      period. This experiment demonstrates that porcine and avian collagen could be
      used as an alternative to bovine collagen in the production of collagen-chitosan
      scaffolding materials.

PMID- 21723968
TI  - Two dimensional difference gel electrophoresis analysis of cerebrospinal fluid in
      tuberculous meningitis patients.
AB  - Tuberculous meningitis (TBM) is a serious complication of tuberculosis that
      affects the central nervous system. Present methods to diagnose TBM are not
      suitable for early diagnosis. Molecular markers and sensitive methods to identify
      them in the early stage of infection of TBM are critically needed for efficient
      management. We have done the proteomic analysis of TBM cerebrospinal fluid (n=20)
      with 2-dimensional difference gel electrophoresis (2D-DIGE) and mass
      spectrometry. We identified 11 human proteins and 8 mycobacterial proteins with
      changed expression levels in comparison to controls. Arachidonate 5-lipoxygenase
      and glial fibrillary acidic protein, two of the identified proteins, were
      validated with western blot technique on a larger set of disease and control
      samples (n=40). These two proteins were also analyzed in fungal meningitis
      samples. We suggest that arachidonate 5-lipoxygenase can be considered for
      validation as a potential marker for diagnosis of TBM.

PMID- 21723969
TI  - Research strategies to improve snakebite treatment: challenges and progress.
AB  - Antivenom is an effective treatment of snakebite but, because of the complex
      interplay of fiscal, epidemiological, therapeutic efficacy and safety issues, the
      mortality of snakebite remains unacceptably high. Efficiently combating this high
      level of preventable death amongst the world's most disadvantaged communities
      requires the globally-coordinated action of multiple intervention programmes.
      This is the overall objective of the Global Snakebite Initiative. This paper
      describes the challenges facing the research community to develop snakebite
      treatments that are more efficacious, safe and affordable than current therapy.

PMID- 21723970
TI  - WISE-2005: bed-rest induced changes in bone mineral density in women during 60
      days simulated microgravity.
AB  - To better understand the effects of prolonged bed-rest in women, 24 healthy women
      aged 25 to 40 years participated in 60-days of strict 6 degrees  head-down tilt
      bed-rest (WISE-2005). Subjects were assigned to either a control group (CON, n=8)
      which performed no countermeasure, an exercise group (EXE, n=8) undertaking a
      combination of resistive and endurance training or a nutrition group (NUT, n=8),
      which received a high protein diet. Using peripheral quantitative computed
      tomography (pQCT) and dual X-ray absorptiometry (DXA), bone mineral density (BMD)
      changes at various sites, body-composition and lower-leg and forearm muscle cross
      sectional area were measured up to 1-year after bed-rest. Bone loss was greatest
      at the distal tibia and proximal femur, though losses in trabecular density at
      the distal radius were also seen. Some of these bone losses remained
      statistically significant one-year after bed-rest. There was no statistically
      significant impediment of bone loss by either countermeasure in comparison to the
      control-group. The exercise countermeasure did, however, reduce muscle cross
      sectional area and lean mass loss in the lower-limb and also resulted in a
      greater loss of fat mass whereas the nutrition countermeasure had no impact on
      these parameters. The findings suggest that regional differences in bone loss
      occur in women during prolonged bed-rest with incomplete recovery of this loss
      one-year after bed-rest. The countermeasures as implemented were not optimal in
      preventing bone loss during bed-rest and further development is required.

PMID- 21723971
TI  - Bone marrow fat has brown adipose tissue characteristics, which are attenuated
      with aging and diabetes.
AB  - Fat occupies a significant portion of bone cavity however its function is largely
      unknown. Marrow fat expands during aging and in conditions which affect energy
      metabolism, indicating that fat in bone is under similar regulatory mechanisms as
      other fat depots. On the other hand, its location may determine specific
      functions in the maintenance of the environment for bone remodeling and
      hematopoiesis. We have demonstrated that marrow fat has a distinctive phenotype,
      which resembles both, white and brown adipose tissue (WAT and BAT, respectively).
      Marrow adipocytes express gene markers of brown adipocytes at levels
      characteristic for the BAT, including transcription factor Prdm16, and regulators
      of thermogenesis such as deiodinase 2 (Dio2) and PGC1alpha. The levels of
      expression of BAT-specific gene markers are decreased in bone of 24 mo old
      C57BL/6 and in diabetic yellow agouti A(vy)/a mice implicating functional changes
      of marrow fat occurring with aging and diabetes. Administration of antidiabetic
      TZD rosiglitazone, which sensitizes cells to insulin and increases adipocyte
      metabolic functions, significantly increased both, BAT (UCP1, PGC1alpha, Dio2,
      beta3AR, Prdm16, and FoxC2) and WAT (adiponectin and leptin) gene expression in
      marrow of normoglycemic C57BL/6 mice, but failed to increase the expression of
      BAT, but not WAT, gene markers in diabetic mice. In conclusion, the metabolic
      phenotype of marrow fat combines both BAT and WAT characteristics. Decrease in
      BAT-like characteristics with aging and diabetes may contribute to the negative
      changes in the marrow environment supporting bone remodeling and hematopoiesis.

PMID- 21723973
TI  - Novel functions for insulin in bone.
AB  - The insulin-like growth factors (IGF) evolved in lower animals to enable a wide
      range of physiologic processes, including smell, food consumption, metabolism,
      growth, reproduction, and dormancy. These functions were accomplished by the
      actions of multiple related ligands that activated a common transmembrane
      receptor protein. In higher organisms, including mammals, the insulin and IGF
      ligands and their receptors evolved to function in a more circumscribed fashion.
      The contemporary model assigns IGFs as central regulators of cell proliferation,
      survival, and organism growth, whereas insulin's action dominates at the level of
      regulation of fuel accumulation, storage, and energy expenditure. Such a
      simplistic paradigm, however, obscures the fact that insulin and IGF-1 continue
      to exert overlapping roles in several physiologic processes. Indeed, recent
      studies have identified previously unappreciated skeletal actions of insulin,
      which suggests that insulin-responsive bone cells participate in the regulation
      of global energy homeostasis. These findings raise intriguing questions on the
      nature of the fuel sensing and processing mechanisms in bone and their relative
      importance to overall energy homeostasis in mammals. Answers to these questions
      should ultimately improve the ability to diagnose and manage patients with
      metabolic diseases such as diabetes and osteoporosis.

PMID- 21723981
TI  - Shanthi V. Sitaraman, MD, PhD: physician, scientist, educator, and humanitarian.

PMID- 21723983
TI  - Introduction to the mentoring, education, and training corner.

PMID- 21723972
TI  - Influence of pre- and peri-natal nutrition on skeletal acquisition and
      maintenance.
AB  - Early life nutrition has substantial influences on postnatal health, with both
      under- and overnutrition linked with permanent metabolic changes that alter
      reproductive and immune function and significantly increase metabolic disease
      risk in offspring. Since perinatal nutrition depends in part on maternal
      metabolic condition, maternal diet during gestation and lactation is a risk
      factor for adult metabolic disease. Such developmental responses may be adaptive,
      but might also result from constraints on, or pathological changes to, normal
      physiology. The rising prevalence of both obesity and osteoporosis, and the
      identification of links among bone, fat, brain, and gut, suggest that obesity and
      osteoporosis may be related, and moreover that their roots may lie in early life.
      Here we focus on evidence for how maternal diet during gestation and lactation
      affects metabolism and skeletal acquisition in humans and in animal models. We
      consider the effects of overall caloric restriction, and macronutrient imbalances
      including high fat, high sucrose, and low protein, compared to normal diet. We
      then discuss potential mechanisms underlying the skeletal responses, including
      perinatal developmental programming via disruption of the perinatal leptin surge
      and/or epigenetic changes, to highlight unanswered questions and identify the
      most critical areas for future research.

PMID- 21723984
TI  - On mentorship.

PMID- 21723985
TI  - GLP-1-based therapies: the dilemma of uncertainty.

PMID- 21723986
TI  - Targeting PI3K signaling as a therapeutic approach for colorectal cancer.
AB  - Survival times of patients with colorectal cancer (CRC) have increased over the
      past decade, primarily as a result of treatment with combinations of conventional
      cytotoxic agents. Because CRC is commonly associated with mutations in genes that
      control growth factor signaling, therapies are being developed to target the
      products of these genes; individualized treatment might also be guided by
      specific mutations in tumors and by new biomarkers. Currently, targeted therapies
      confer limited clinical benefit; better drugs are therefore needed. Genomic
      studies indicate that phosphoinositide 3-kinase (PI3K) signaling is one of the
      most frequently deregulated pathways in several human cancers, including CRC.
      PI3K signaling has an important role in cancer cell proliferation, survival,
      motility, and metabolism and therefore could be an attractive therapeutic target.
      We review PI3K signaling in CRC and discuss current therapeutic approaches.

PMID- 21723987
TI  - Elective edentulation after 7 episodes of infective endocarditis: a clinical
      report.

PMID- 21723988
TI  - Efficient prosthodontic treatment in a young patient with long-standing bulimia
      nervosa: A clinical report.
AB  - Time-saving, efficient dental treatment is essential for patients in poor dental
      condition. This clinical report describes a systematic technique for restoration
      of the visibly-destroyed dentition of a long-term bulimia nervosa patient,
      including occlusal vertical dimension increase, with composite resin core
      foundations and prosthetic rehabilitation with ceramic crowns, in only a few
      treatment sessions. The efficiency of this procedure is gained from composite
      resin core restorations that establish the new occlusal vertical dimension (OVD)
      and replace and form the foundation for the subsequent crown preparation.

PMID- 21723989
TI  - Randomized, prospective, clinical evaluation of prosthodontic modalities for
      mandibular implant overdenture treatment.
AB  - STATEMENT OF PROBLEM: Mandibular implant overdentures provide improved treatment
      outcome than conventional denture therapy, but there is controversy as to which
      overdenture treatment is the best choice. PURPOSE: This study evaluated 3
      different mandibular implant overdenture treatments with respect to prosthesis
      retention and stability, tissue response, patient satisfaction and preference,
      and complications to determine treatment outcomes. MATERIAL AND METHODS: In a
      prospective, randomized clinical trial, using a crossover design, 30 subjects
      (mean age, 58.9; 63% male) received 4 implants in the anterior mandible. For each
      subject, 3 different overdenture attachment types were fabricated and/or fitted
      to the implants. These included a 4-implant bar attachment fitted to all 4
      implants, a 2-implant bar attachment, and 2 independent ball attachments.
      Subjects were randomly assigned to 1 of 6 possible treatment sequences and
      received all 3 attachment types each for approximately 1 year. Data were
      collected at baseline, and at 6 and 12 months for treatment types. Denture
      retention and stability and parameters of soft tissue response were recorded.
      Complications were documented and questionnaires were used to identify subject
      masticatory ability, denture complaints, and preferences. Data were analyzed to
      determine statistical equivalence among the 3 different treatments using the
      Schuirmann's two one-sided test (TOST) procedure, and the Wilcoxon-Mann-Whitney
      TOST procedure (alpha=.05). RESULTS: Force gauge prosthesis retention
      measurements showed that the 3 treatment types were not statistically equivalent,
      with the 4-implant bar demonstrating the greatest retention. Criterion-based
      retention scores were statistically equivalent for all treatments. Both the force
      gauge and criterion-based prosthesis stability measurements were statistically
      equivalent among all 3 treatment types. Analysis of all other multiple criterion
      based scoring systems indicated the majority of these variables demonstrated
      equivalence. Where equivalence was not identified, the most favorable responses
      were typically found with the O-ring treatment, and the least favorable with the
      4-implant bar treatment. From the small percentage of treatment visits
      demonstrating minor complications, no single treatment presented with greater
      complications than the others. For the treatment preference among subjects, 52%
      selected the independent ball attachment, 32% the 4-implant bar, and 16% the 2
      implant bar (P=.10). CONCLUSIONS: The 2-implant independent treatment used in
      this study provided equivalent or more favorable treatment outcomes for most
      measured parameters relative to the more complex and costly 2- and 4-implant bar
      attachments. The 4-implant bar treatment provided greater prosthesis retention
      than the other treatment types in this study, but after experience with all
      systems, subjects were more satisfied with and preferred the independent implant
      treatment.

PMID- 21723990
TI  - Estimating long-term survival of densely sintered alumina crowns: a cohort study
      over 10 years.
AB  - STATEMENT OF PROBLEM: Alumina-core crowns have become a standard treatment option
      in contemporary dental practice. The short-term survival of alumina crowns has
      been well documented. However, there is still a paucity of long-term survival
      data. PURPOSE: The purpose of this prospective cohort study was to estimate long
      term survival of alumina crowns in anterior and posterior areas over an
      observation period of up to 10 years. MATERIAL AND METHODS: Between 1997 and
      2005, 155 alumina crowns were placed in 50 subjects. Clinical and technical
      parameters were assessed at baseline. In 2005 and 2008, the crowns were
      clinically assessed using modified U.S. Public Health Service (USPHS) guidelines.
      Treatment failure was defined as crown or tooth loss and separated into technical
      or biological failures. Survival probabilities were estimated using the Kaplan
      Meier method. RESULTS: In 2008, 29 subjects with 112 alumina crowns, including 86
      (77%) posterior and 26 (23%) anterior crowns, were available for clinical
      assessment. The average observation period for these subjects was 7.8 years, with
      a range from 3 to 10.7 years. In total, 3 technical and 8 biological failures
      were observed. The estimated survival probability considering technical failures
      only was 95% (95% Confidence Interval (CI), 89% to 100%). The estimated overall
      survival probability after 10 years was 84% (95% CI, 74% to 95%). There was no
      significant difference in treatment failures in posterior as compared to anterior
      crowns (all failures: P=.713; technical failures: P=.352). CONCLUSIONS: The
      results suggest that the expected 10-year survival rate of alumina crowns due to
      technical failures is 95% (95% CI, 89% to 100%).

PMID- 21723991
TI  - Shear bond strengths of pressed and layered veneering ceramics to high-noble
      alloy and zirconia cores.
AB  - STATEMENT OF PROBLEM: Heat-pressed ceramics to metal alloys and zirconia have
      been available for some time. However, information regarding their shear bond
      strengths is limited. PURPOSE: The purpose of this study was to evaluate the
      shear bond strengths of heat-pressed and layered ceramics with regard to their
      corresponding high-noble alloy and zirconia cores. MATERIAL AND METHODS: Forty
      cylinders (approx. 5 mm in diameter) of high-noble alloy (Olympia) were cast and
      divided into 4 groups (n=10). Metal cylinders were veneered with ceramics to
      produce shear test specimens: Group PMI with IPS InLine POM; Group LMI with IPS
      InLine; Group PMC with Pulse press-to-metal; and Group LMC with Authentic Pulse
      Metal ceramic. Forty cylinders (approx. 5 mm in diameter) of zirconia (Lava) were
      obtained and divided into 4 groups (n=10). These cylinders were veneered with
      ceramics to produce shear test specimens: Group PZI with IPS e.max ZirPress;
      Group LZI with IPS e.max. Ceram; Group PZV with VITA PM9; and Group LZV with VITA
      VM9. The veneering ceramics, 3 mm in thickness, were either pressed or layered to
      their corresponding cylinders. Thermal cycling was performed at 5 degrees C and
      55 degrees C for 20,000 cycles with a 20 second dwell time. Shear bond strength
      testing was conducted in a universal testing machine, and the failure strengths
      were recorded. Fracture surfaces were characterized visually, under a
      stereomicroscope, and with a scanning electron microscope (SEM). Data were
      analyzed using rank-based Kruskal-Wallis and Mann-Whitney tests with Bonferroni
      correction to adjust for multiple comparisons (alpha=.05). RESULTS: For metal
      ceramic specimens, the mean (SD) shear bond strengths ranged from 37.8 (20.6) MPa
      to 66.4 (22.1) MPa. There were significant differences between Groups PMI and PMC
      and between Groups LMI and PMC, in which Groups PMI and LMI had significantly
      higher strength values than Group PMC (P=.041). For zirconia ceramic specimens,
      the mean (SD) shear bond strengths ranged from 30.03 (9.49) MPa to 47.2 (13.0)
      MPa, with Group LZV having a significantly higher shear bond strength value than
      Group LZI (P=.012). Half of the Group PZV specimens failed during thermal
      cycling, and Group PZV was, therefore, excluded from statistical analysis. For
      all shear bond strength testing specimens, cohesive failures in the veneering
      ceramics were observed. CONCLUSIONS: For shear bond strength of veneering
      ceramics to high-noble alloy, there was no significant difference between
      pressing and layering with the same manufacturer. For shear bond strength of
      veneering ceramics to zirconia, there was no significant difference between the
      pressed and layered groups.

PMID- 21723992
TI  - Color change during the surface preparation stages of metal ceramic alloys.
AB  - STATEMENT OF PROBLEM: Even though metal ceramic restorations (MCRs) are widely
      used by clinicians, the influence of the metal on the color of overlaying
      porcelain is unknown. PURPOSE: The purpose of this study was to analyze the color
      alterations of different types of metal ceramic alloys during several stages of
      metal surface preparation and to determine the effect of those changes on the
      resulting color of opaque porcelain (OP). MATERIAL AND METHODS: Seven different
      types of alloys (3 base metal, 3 noble, and 1 high noble) were used to prepare
      disk-shaped specimens (1 mm * 10 mm, n=3), followed by OP application (0.1 mm).
      L*a*b* values of specimens were recorded after different stages of metal surface
      preparation (ingot, after casting, after oxidation, and after the OP application)
      in addition to the shade tab of OP B1 (target shade). L*a*b* values of alloys
      were measured from the ingot structure to the OP application stage and
      statistically analyzed (Repeated measures ANOVA, and Bonferroni corrected paired
      t test, alpha=.05). L*a*b* values of OP applied groups and the OP shade tab
      (target shade) were analyzed (1-way ANOVA with Dunnett's multiple comparison
      test, alpha=.05). The color differences of the target shade both before and after
      OP application were calculated and statistically analyzed (1-way ANOVA, Ryan
      Einot-Gabriel-Welsch Multiple Range Test, alpha=.05). RESULTS: The L* values of
      all alloys changed significantly after each stage except for 2 alloys (V-Deltaloy
      SF (N-VDSF)) and (Gnathos Plus (HN-GP)) after casting and airborne-particle
      abrasion (P<.05). The a* value of all alloys increased after casting. Changes in
      the a* coordinate were significant except for one of the base metal alloys
      (P<.05). The a* coordinate changes of alloys showed variation in direction after
      oxidation and OP application (P<.05). The b* coordinate changes of alloys showed
      variation in direction after each stage (P<.05). The L*a*b* values of some OP
      applied alloys were significantly different from that of the OP shade tab
      (P<.05). Color difference values (DeltaE (OP applied alloy-target shade)) of 2 OP
      applied alloys (Cerapall 2 (N-CP2) and Ceradelta (N-CD)) were significantly
      different (P<.05) and higher than the other OP-applied alloys. CONCLUSIONS: The
      achromatic color behavior of different alloys was all in the same direction at
      all metal surface preparation stages. The chromatic behavior of the different
      alloys was primarily towards the same direction after casting and airborne
      particle abrasion, whereas it varied after oxidation and OP application. The
      color difference of OP for all alloys, regardless of their type, was not visually
      perceivable when compared to the target shade (DeltaE<2.6).

PMID- 21723993
TI  - Survey of partial removable dental prosthesis (partial RDP) types in a distinct
      patient population.
AB  - STATEMENT OF PROBLEM: Current demographic information on the number and types of
      removable partial dentures is lacking in the prosthodontic literature. PURPOSE:
      This study was designed to investigate patterns of tooth loss in patients
      receiving removable partial dentures (RPDs) in eastern Wisconsin. MATERIAL AND
      METHODS: Digital images (1502) of casts at 5 dental laboratories in eastern
      Wisconsin were collected. Any prescription requesting fabrication of a removable
      partial denture was photographed twice. The first photograph was made immediately
      upon arrival at the laboratory, while the second photograph was made immediately
      before being returned to the prescribing dentist for the first time. A calibrated
      investigator analyzed all the photographs for Kennedy Classification, type of
      RPD, major connector, and other details. Data were analyzed with descriptive
      statistics. Fisher's exact test was used to confirm repeatability. RESULTS:
      Kennedy Class I was the most common RPD with a frequency of 38.4%. More than 40%
      of prescriptions had no design input from the dentist. One in 3 RPDs used acrylic
      resin or flexible frameworks. One in 5 RPDs had no rests. The horseshoe major
      connector was the most common maxillary major connector, while the lingual plate
      was the most common in the mandible. CONCLUSIONS: RPDs remain a common
      prosthodontic treatment in this region. Non-metal RPD frameworks are a common
      treatment type and rarely include rests. These data indicate a changing partially
      edentulous patient population and a variable commitment to standard levels of
      prosthodontic care.

PMID- 21723994
TI  - A technique for fabricating a 2-part surgical template.

PMID- 21723995
TI  - A technique for removing a fractured rotary cutting instrument from a high-speed
      handpiece.

PMID- 21723996
TI  - Parental strategies and trajectories of peer victimization in 4 to 5 year olds.
AB  - This study was designed to examine how parental strategies contribute to
      explaining trajectories of peer victimization in young children. A total of 73 4
      and 5 year old children identified as victims of peer aggression in the fall
      semester and their parents were recruited from 46 classrooms in 18 schools in the
      Netherlands. All children were followed-up twice in order to determine for whom
      victimization was stable. Hypothetical vignettes describing various forms of
      victimization were presented to one parent of each child in order to assess
      parental responses to victimization events. Findings indicated that autonomy
      supporting and autonomy neutral strategies were associated with a decrease of
      victimization in the first semester of the school year. No protective effects
      were found in the second semester. Autonomy undermining strategies were not
      related to the course of peer victimization. These findings underscore the
      importance of joint and coordinated efforts of teachers and parents as partners
      in supporting victimized young children at school.

PMID- 21723997
TI  - The impact of school connectedness on violent behavior, transport risk-taking
      behavior, and associated injuries in adolescence.
AB  - Adolescents engage in many risk-taking behaviors that have the potential to lead
      to injury. The school environment has a significant role in shaping adolescent
      behavior, and this study aimed to provide additional information about the
      benefits associated with connectedness to school. Early adolescents aged 13 to 15
      years (N=509, 49% boys) were surveyed about school connectedness, engagement in
      transport and violence risk-taking, and injury experiences. Significant relations
      were found between school connectedness and reduced engagement in both transport
      and violence risk-taking, as well as fewer associated injuries. This study has
      implications for the area of risk-taking and injury prevention, as it suggests
      the potential for reducing adolescents' injury through school based interventions
      targeting school connectedness.

PMID- 21723998
TI  - We're all in this together now: group performance feedback to increase classroom
      team data collection.
AB  - This study's primary goal was to evaluate the use of performance feedback
      procedures delivered to a classroom team to increase daily data collection.
      Performance feedback (PFB) was delivered to four classroom teams responsible for
      the daily collection of data representing student performance during prescribed
      instructional activities. Using a multiple-baseline design, the effects of the
      team performance-feedback were evaluated for the target student, and for
      generalization to data collection for all classroom students. A secondary
      question evaluated if student on-task behavior correlated with increased data
      collection. Finally, social validity was investigated to evaluate team
      satisfaction with the PFB intervention. The results demonstrate improved data
      collection across all four classroom teams for the target student in each
      classroom and generalization within classrooms to all remaining students. Slight
      increases in student on-task behavior were observed in three of the four
      classrooms, and teacher satisfaction ratings were high.

PMID- 21723999
TI  - An investigation of the partial-assignment completion effect on students'
      assignment choice behavior.
AB  - This study was designed to investigate the partial assignment completion effect.
      Seventh-grade students were given a math assignment. After working for 5 min,
      they were interrupted and their partially completed assignments were collected.
      About 20 min later, students were given their partially completed assignment and
      a new, control assignment that contained the same number of equivalent problems
      that were incomplete on their partially completed assignment. Students were told
      that they would have to complete an assignment but could choose which assignment
      they completed. Significantly more students chose their partially completed
      assignment. Theoretical and applied implications and directions for future
      research are discussed.

PMID- 21724000
TI  - Stability of peer victimization in early adolescence: effects of timing and
      duration.
AB  - The current study investigated the stability of peer victimization and the impact
      of the timing and duration of victimization on psychological and academic
      outcomes for boys and girls on a sample of 863 middle school students. Results
      demonstrated strong support for the onset hypothesis and concurrent effects of
      maladjustment in anxiety, depression, self-esteem, poor school attitude, GPA, and
      attendance. Support for the cessation hypothesis was mixed, depending on the
      outcome and gender: boys demonstrated recovery from internalizing distress,
      whereas girls demonstrated residual effects, even after the cessation of
      victimization. Girls also demonstrated residual effects of victimization on
      grades, and both boys and girls evidenced residual effects of victimization on
      attendance. Regarding duration of victimization, there was strong support for the
      life-events model of stress and coping across almost all outcomes, suggesting
      that even temporary experiences of victimization could have a negative impact on
      psychological and academic outcomes. Overall, results demonstrated the importance
      of considering the timing and duration of victimization in understanding the
      risks and damaging effects of victimization. The results from this study also
      highlight both the need and the potential to intervene during early adolescence
      when peer relationships are taking on increasing importance, as well as the
      importance of helping students regain social-emotional and academic functioning,
      even after victimization ceases.

PMID- 21724001
TI  - The assessment of school engagement: examining dimensionality and measurement
      invariance by gender and race/ethnicity.
AB  - The construct of school engagement has attracted growing interest as a way to
      ameliorate the decline in academic achievement and increase in dropout rates. The
      current study tested the fit of a second-order multidimensional factor model of
      school engagement, using large-scale representative data on 1103 students in
      middle school. In order to make valid model comparisons by group, we evaluated
      the extent to which the measurement structure of this model was invariant by
      gender and by race/ethnicity (European-American vs. African-American students).
      Finally, we examined differences in latent factor means by these same groups.
      From our confirmatory factor analyses, we concluded that school engagement was a
      multidimensional construct, with evidence to support the hypothesized second
      order engagement factor structure with behavioral, emotional, and cognitive
      dimensions. In this sample, boys and girls did not substantially differ, nor did
      European-American and African-American students, in terms of the underlying
      constructs of engagement and the composition of these constructs. Finally, there
      were substantial differences in behavioral and emotional engagement by gender and
      by racial/ethnic groups in terms of second-order factor mean differences.

PMID- 21724002
TI  - Professional well-being work party of WFSA: it is time to think and take action
      regarding the occupational health of anesthesiologists.

PMID- 21724003
TI  - Clinical evaluation of two Ke0 in the same pharmacokinetic propofol model: study
      on loss and recovery of consciousness.
AB  - BACKGROUND AND OBJECTIVE: The constant equilibrium between the plasma and effect
      site (ke0) is used by pharmacokinetic models to calculate a drug concentration in
      its site of action (Ce). It would be interesting if Ce of propofol was similar at
      loss and recovery of consciousness. The objective of this study was to evaluate
      the clinical performance of two different ke0 (fast = 1.21 min(-1), and slow =
      0.26 min(-1)) in relation to Ce during loss and recovery of consciousness using
      Marsh pharmacokinetic model. METHODS: Twenty healthy adult male volunteers
      participated in this study. In all volunteers propofol was administered as target
      controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different
      time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol
      was infused with a serum target-controlled infusion of 3.0 MUg.mL(-1). Loss of
      consciousness and recovery of consciousness were based on response to verbal
      stimulus. Ce was recorded at the moment of loss and recovery of consciousness.
      RESULTS: On loss and recovery of consciousness, the Ce for fast ke0 was different
      (3.64 +/- 0.78 and 1.47 +/- 0.29 MUg.mL(-1), respectively, p < 0.0001), while
      with slow ke0 the Ce was similar (2.20 +/- 0.70 and 2.14 +/- 0.43 MUg.mL(-1),
      respectively, p = 0.5425). CONCLUSIONS: Clinically, the slow ke0 (0.26 min(-1))
      incorporated in the Marsh pharmacokinetic model showed better performance than
      the fast ke0 (1.21 min(-1)), since the calculated concentration of propofol at
      the effect site on loss and recovery of consciousness was similar.

PMID- 21724004
TI  - Effects of prophylactic continuous infusion of phenylephrine on reducing the mass
      of local anesthetic in patients undergoing spinal anesthesia for cesarean
      section.
AB  - BACKGROUND AND OBJECTIVES: Reducing the mass of local anesthetic minimizes the
      effects of hypotension after spinal anesthesia for cesarean section and the
      incidence of maternal adverse events preserving fetal well-being, but it may
      result in insufficient anesthesia. Hypotension associated with greater masses of
      subarachnoid anesthesia can be controlled by prophylactic continuous infusion of
      phenylephrine. The effects of prophylactic continuous infusion of phenylephrine
      on pressure control on maternal and fetus results in cesarean sections with
      different doses of hyperbaric bupivacaine in spinal anesthesia. METHODS: A non
      randomized prospective study of 60 gravidas at term scheduled for elective
      cesarean sections was undertaken. Patients were allocated into two groups
      depending on hyperbaric bupivacaine dose administered for spinal anesthesia, 12
      or 8 mg, along with 5 MUg of sufentanil and 100 MUg of morphine. Patients were
      hydrated with 10 mL.kg(-1) of Ringer's lactate before the anesthesia. Shortly
      after, continuous infusion of 100 MUg.min(-1) of phenylephrine was initiated to
      maintain blood pressure at baseline levels. The following parameters were
      evaluated: level of anesthetic blockade, consumption of vasopressors, incidence
      of maternal events, and conditions of the newborn. RESULTS: Maternal data was
      similar in both groups regarding the level of anesthetic blockade, phenylephrine
      consumption along time, incidence of hypotension, hypertension, bradycardia,
      nausea, vomiting, dyspnea, pain, and tremors. Conceptual data showed similarities
      between both groups regarding blood gases and umbilical vein lactate levels. The
      pH of all newborns was > 7.2. CONCLUSIONS: On maintaining the blood pressure with
      prophylactic continuous infusion of phenylephrine the incidence of maternal
      adverse events and conditions of birth do not differ whether spinal anesthesia is
      performed with 12 mg or 8 mg of hyperbaric bupivacaine.

PMID- 21724005
TI  - Incidence of regional pain syndrome after carpal tunnel release. Is there a
      correlation with the anesthetic technique?
AB  - BACKGROUND AND OBJECTIVES: Complex regional pain syndrome (CRPS) previously known
      as reflex sympathetic dystrophy refers to a set of signs and symptoms that
      include pain, increased sweating, and vasomotor instability. Pain is usually
      triggered by a noxious stimulus in a peripheral nerve, which is disproportionate
      to the triggering stimulus. Its development after surgery is not uncommon varying
      with the type of intervention. An incidence of 2.1 to 5% has been reported after
      carpal tunnel release (CTR). Sympathetic blockade may prevent the onset of CRPS.
      However, there is no study validating this technique to prevent CRPS after CTR.
      The objective of the present study was to define the incidence of CRPS after CTR
      and its relationship with four anesthetic techniques. METHODS: Patients were
      randomly distributed to undergo one of the following techniques: general
      anesthesia, regional intravenous anesthesia with lidocaine, regional intravenous
      anesthesia with lidocaine and clonidine, or axillary plexus block.
      Postoperatively, they were followed-up by a nurse who was unaware of the
      anesthetic technique used, and follow-up was done through electronic patient
      records for up to 6 months after the anesthesia. During this period signs and
      symptoms typical of CRPS were investigated and, if positive, treatment was
      instituted. A descriptive evaluation using the chi-square test was performed.
      RESULTS: Three-hundred and one patients were investigated. Twenty-five of them
      developed CRPS, an incidence of 8.3%. Predominance was not observed among the
      anesthetic techniques used. Other factors such as smoking, profession, and other
      concomitant diseases were also investigated, and none showed a relationship with
      the development of post-CTR CRPS. CONCLUSIONS: Complex regional pain syndrome has
      an incidence of 8.3% after CTR surgery without association with the anesthetic
      techniques investigated.

PMID- 21724006
TI  - Hemodynamic changes during myocardial revascularization without extracorporeal
      circulation.
AB  - BACKGROUND AND OBJECTIVES: Cardiac positioning and stabilization during
      myocardial revascularization without extracorporeal circulation (ECC) may cause
      hemodynamic changes dependent to the surgical site. The objective of this study
      was to evaluate these changes during distal coronary anastomosis. METHODS: Twenty
      adult patients undergoing myocardial revascularization without ECC were monitored
      by pulmonary artery catheter and transesophageal Echo Doppler. Hemodynamic data
      were collected at the following times before removing the stabilizer wall: (1)
      after volume adjustments, (2) at the beginning of distal anastomosis, and (3)
      after 5 minutes. Treated coronary arteries were grouped according to their
      location in the lateral, anterior, or posterior wall. Two-way ANOVA with
      repetition and Newman-Keuls post-test were used in the analysis. A p value < 0.05
      was considered statically significant. RESULTS: During myocardial
      revascularization without ECC, pulmonary artery wedge pressure showed elevation
      from 17.7 +/- 6.1 to 19.2 +/- 6.5 (p < 0.001) and 19.4 +/- 5.9 mmHg (p < 0.001),
      while the central venous pressure went from 13.9 +/- 5.4 to 14.9 +/- 5.9 mmHg (p
      = 0.007) and 15.1 +/- 6.0 mmHg (p = 0.006). Intermittent cardiac output was
      reduced from 4.70 +/- 1.43 to 4.23 +/- 1.22 (p < 0.001) and 4.26 +/- 1.25 L.min(
      1) (p < 0.001). According to transesophageal Doppler, a significant group-time
      interaction was observed in cardiac output, which was reduced in the lateral
      group from 4.08 +/- 1.99 to 2.84 +/- 1.82 (p = 0.02) and 2.86 +/- 1.73 L.min(-1)
      (p = 0.02), and aortic blood flow, which went from 2.85 +/- 1.39 to 1.99 +/- 1.26
      (p = 0.02) and 2.00 +/- 1.21 L.min(-1) (p = 0.02). Other hemodynamic changes were
      not observed during anastomoses. CONCLUSIONS: A significant hemodynamic
      deterioration was observed during myocardial revascularization without ECC.
      Transesophageal Doppler detected a decrease in cardiac output only in the lateral
      group.

PMID- 21724007
TI  - Comparison between the hemodynamic parameters of rigid laryngoscopy and lighted
      stylet in patients with coronariopathies.
AB  - BACKGROUND AND OBJECTIVES: Anesthesiologists are responsible for airway
      management whenever they assume the anesthesia of a patient. In this study, we
      compare the hemodynamic parameters of rigid laryngoscopy and lighted stylet in
      patients with coronariopathies. PATIENTS AND METHODS: This randomized clinical
      trial included 40 patients undergoing myocardial revascularization assigned into
      two groups: lighted stylet and rigid laryngoscope. Besides time of tracheal
      intubation in each group, heart rate, mean arterial pressure, changes in ST
      segment, and central venous pressure were evaluated during patient preparation, 1
      minute and 5 minutes after anesthetic induction, and 1 minute after tracheal
      intubation. RESULTS: Both groups were homogenous regarding demographic data. Time
      of tracheal intubation in the rigid laryngoscope group (24 +/- 5 sec) was lower
      than that of the lighted stylet group (28 +/- 7 sec), but without significance.
      Heart rate showed a reduction in both groups during anesthetic induction (p <
      0.05), but 1 minute after tracheal intubation the heart rate increased to levels
      close to baseline levels in both groups (p > 0.05). In the rigid laryngoscope
      group mean arterial pressure increased after tracheal intubation to levels close
      to those observed during patient preparation (p > 0.05), while in the lighted
      stylet group mean arterial pressure remained below baseline levels (p < 0.05).
      Central venous pressure increased on both groups at all times (p < 0.05).
      CONCLUSIONS: It was possible to observe that both techniques are safe for
      tracheal intubation in patients with coronariopathies. However, lighted stylet
      has fewer repercussions on mean arterial pressure.

PMID- 21724008
TI  - Hydroelectrolytic balance and cerebral relaxation with hypertonic isoncotic
      saline versus mannitol (20%) during elective neuroanesthesia.
AB  - BACKGROUND AND OBJECTIVES: Cerebral relaxation during intracranial surgery is
      necessary, and hiperosmolar therapy is one of the measures used to this end.
      Frequently, neurosurgical patients have sodium imbalances. The objective of the
      present study was to quantify and determine cerebral relaxation and duration of
      hydroelectrolytic changes secondary to the use of mannitol versus hypertonic
      isoncotic solution (HIS) during neurosurgery. METHODS: Cerebral relaxation and
      hydroelectrolytic changes were evaluated in 29 adult patients before de beginning
      of infusion, and 30 and 120 minutes after the infusion of equiosmolar loads of
      approximately 20% mannitol (250 mL) or HIS (120 mL). The volume of intravenous
      fluids infused and diuresis were recorded. A p < 0.05 was considered significant.
      RESULTS: A statistically significant difference in cerebral relaxation between
      both groups was not observed. Although several changes in electrolyte levels and
      acid-base balance with mannitol or HIS reached statistical significance only the
      reduction in plasma sodium 30 minutes after infusion of mannitol, mean of 6.42 +/
      0.40 mEq.L(-1), and the increase in chloride, mean of 5.41 +/- 0.96 mEq.L(-1)
      and 5.45 +/- 1.45 mEq.L(-1) 30 and 120 minutes after infusion of HIS, caused a
      transitory dislocation of serum ion levels from normal range. The mannitol (20%)
      group had a significantly greater diuresis at both times studied compared with
      HIS group. CONCLUSIONS: A single dose of hypertonic isoncotic saline solution
      [7.2% NaCl/6% HES (200/0.5)] and mannitol (20%) with equivalent osmolar loads
      were effective and safe in producing cerebral relaxation during elective
      neurosurgical procedures under general anesthesia.

PMID- 21724009
TI  - Anaesthesia for caesarean section in a patient with lumbar syringomyelia.
AB  - BACKGROUND AND OBJECTIVES: Syringomyelia is a rare neurological condition
      characterized by the presence of an expansive cystic cavity in the spinal cord,
      resulting in several neurologic manifestations. The objective of the present
      report was to address the safety of general anesthesia in this group of patients.
      CASE REPORT: This is a 28-year old primipara with lumbar syringomyelia scheduled
      for lower segment cesarean section (LSC). Surgery was performed under general
      anesthesia without complications. General anesthesia was chosen for this patient
      to avoid manipulation of the subarachnoid space during neuraxial anesthesia,
      which could cause changes in intracranial pressure or worsening neurological
      symptoms. We used rocuronium considering that it avoids rising in cerebrospinal
      fluid pressure and hyperkalemia that can be seen with succinylcholine.
      CONCLUSIONS: General anesthesia can be safely used in patients with
      syringomyelia. Care should be taken to prevent increase in intracranial pressure
      and neuromuscular blockade should be monitored.

PMID- 21724010
TI  - Retrograde orotracheal intubation with a double-lumen tube.
AB  - BACKGROUND AND OBJECTIVES: Difficult airway management in thoracic surgeries is a
      peculiar subject due to the demands of monopulmonary ventilation with double
      lumen tubes. Flexible bronchoscopy guidance is extremely important, but it is not
      always available. The objective of this report was to describe a case of
      retrograde selective orotracheal intubation in the absence of specific endoscopy
      equipment for the procedure. CASE REPORT: This is a patient with a history of
      retosigmoidectomy, admitted for a right thoracotomy for a lung lesion.
      Preoperative anesthetic evaluation did not reveal any clinical and physical exam
      particularities. After anesthetic induction and ventilation with face mask, two
      attempts of orotracheal intubation under direct laryngoscopy were ineffective due
      to difficult visualization of the vocal folds (Cormack-Lehane grade III). Due to
      the unavailability of specific material for selective endoscopic intubation it
      was decided to use the retrograde technique using the double-lumen tube. The
      patient was extubated in the operating room shortly after the end of the surgery
      without complications secondary to the alternative technique. CONCLUSIONS:
      Retrograde selective orotracheal intubation is a minimally invasive technique,
      low cost, safe, and extremely useful whenever flexible bronchoscopy is not
      available.

PMID- 21724011
TI  - Takayasus's arteritis in pregnancy. Case report and literature review.
AB  - BACKGROUND AND OBJECTIVES: Takayasus's Arteritis (TA) is a chronic, inflammatory,
      progressive, idiopathic disease that causes narrowing, occlusion, and aneurysms
      of systemic and pulmonary arteries affecting especially the aorta and its
      branches. During pregnancy, one should pay special attention to these patients.
      The objective of this report was to present the peripartum anesthetic care of a
      patient with TA and a review of the literature. CASE REPORT: This is a 31-year
      old gravida who underwent exchange of the aortic arch and placement of a metallic
      aortic valve for TA four years ago. She had no complications during pregnancy,
      and she was admitted at 34 weeks of pregnancy for anticoagulation management.
      Elective cesarean section was performed at 39 weeks with continuous epidural
      anesthesia. Fractionated doses of local anesthetic were administered to guarantee
      slow installation of the blockade. The patient remained hemodynamically stable
      and was transferred to the ICU in the postoperative period. CONCLUSIONS: Several
      complications can affect gravidas with TA. Careful patient evaluation, treatment
      of TA complications, and anestheticsurgical planning are fundamental. Maintenance
      of perfusion is the main concern in these patients, and neuraxial blocks may be
      used without harming the mother and fetus. In patients with compensated TA
      complications, monitoring does not differ from that routinely used in cesarean
      sections. Continuous epidural anesthesia with slow installation maintains
      hemodynamic stability and allows monitoring cerebral perfusion through the level
      of consciousness. To avoid postoperative hypoperfusion or hypertensive
      complications patients should be monitored in an intensive or semi-intensive care
      unit for 24 hours.

PMID- 21724012
TI  - Assessment of the stress level of anesthesiologists of the Sergipe
      anesthesiologists cooperative.
AB  - BACKGROUND AND OBJECTIVES: To assess the impact caused by stress on occupational
      health of anesthesiologists in Sergipe and to propose solutions to improve work
      conditions, quality of the service provided, and quality of life. METHODS: WHOQOL
      BREF questionnaire was applied; the sample size was determined by the Barbetta
      method; and Student t test and Analysis of Variance were used for intergroup
      comparisons, considering significant a p < 5%. RESULTS: This study demonstrated
      that the mean weekly working hours is 61.33 hours. In the subjective analysis of
      quality of life, 53.1% of the respondents had a negative or non-established
      evaluation. On the item "leisure activities", 61.2% answered they have very few
      opportunities or none at all, demonstrating agreement with personal satisfaction
      and working assessment. The age group of 41 to 52 years old had the best scores.
      A significant difference regarding gender and number of working days/week was not
      observed. The general domain had lower scores than the others in all variables
      analyzed. CONCLUSIONS: Excessive working load contributed to a negative self
      evaluation on quality of life, besides hindering access to leisure activities.
      The implementation of a quality policy in work institutions, as well as a
      personal reevaluation in search of innovation, professional recycling, leisure
      alternatives, and motivation are factors that can contribute to improve the
      quality of life and work of these professionals.

PMID- 21724013
TI  - Intraoperative monitoring with transesophageal echocardiography in cardiac
      surgery.
AB  - BACKGROUND AND OBJECTIVES: Since its clinical introduction in the 80s,
      intraoperative transesophageal echocardiography (TEE) has represented one of the
      greatest advances in modern cardiac anesthesia. It is a semi-invasive technique
      that allows direct and fast visualization of structural anatomy of the heart and
      great vessels as well as contributes to hemodynamic and functional evaluation of
      the cardiovascular system. Thus, it has become an important monitor in aiding the
      diagnosis of cardiac pathologies and anesthesia and surgical interventions. The
      objective of this report was to perform a comprehensive review on the use of
      intraoperative TEE in cardiac surgery. CONTENTS: This article reviews some
      aspects of ultrasound physics, imaging techniques, echocardiographic cuts used
      more oftenly, indications, and main clinical applications in addition to
      contraindications and complications. CONCLUSIONS: Intraoperative TEE is a safe
      method of cardiovascular monitoring, which is useful in the formulation of a
      surgical strategy, orientation of hemodynamic interventions, and immediate
      assessment of surgical outcomes. Once qualified to use the method, the
      anesthesiologist expands its role in perioperative medicine, providing clinical
      information necessary to the anesthetic-surgical procedure in cardiac surgery.

PMID- 21724014
TI  - Glass ampoules: risks and benefits.
AB  - BACKGROUND AND OBJECTIVES: Glass ampoules have been widely used in packaging
      injection drugs. Glass has important characteristics that allow it to be widely
      used in fabrication of recipients for drugs and other sterile substances.
      However, contamination of solutions with glass microparticles on breaking open
      glass ampoules, the presence of metals, percutaneous injury, and biological
      contamination justify the need of educational materials to orient the
      manipulation of ampoules. CONTENTS: Glass microparticles generated in the snap
      opening of ampoules, as well as metals that contaminate their contents can be
      aspirated and injected through several routes. Exogenous contaminations by glass
      and metals can reach several sites in the organism. They trigger organic
      reactions that may give rise to injuries. Opening ampoules can expose
      professionals to the risk of percutaneous injuries. These lesions increase the
      biological risk as they are the gateway for viruses and bacteria. Ampoules
      opening systems (VIBRAC and OPC) have been developed to reduce the incidence of
      such accidents. Alternative materials to glass may represent an interesting
      strategy to increase safety. The use of prefilled syringes may represent an
      evolution regarding safety. CONCLUSIONS: Team training and information provided
      by the pharmaceutical industry on the use of ampoules are fundamental in the
      prophylaxis of accidents and contaminations. The search for safer materials to
      replace glass is also important.

PMID- 21724015
TI  - New recommendations for cardiopulmonary resuscitation and emergency
      cardiovascular care.

PMID- 21724016
TI  - Spinal or epidural analgesia? Difference in methods.

PMID- 21724017
TI  - p53 Superfamily proteins in marine bivalve cancer and stress biology.
AB  - The human p53 tumour suppressor protein is inactivated in many cancers and is
      also a major player in apoptotic responses to cellular stress. The p53 protein
      and the two other members of this protein family (p63, p73) are encoded by
      distinct genes and their functions have been extensively documented for humans
      and some other vertebrates. The structure and relative expression levels for
      members of the p53 superfamily have also been reported for most major
      invertebrate taxa. The functions of homologous proteins have been investigated
      for only a few invertebrates (specifically, p53 in flies, nematodes and recently
      a sea anemone). These studies of classical model organisms all suggest that the
      gene family originally evolved to mediate apoptosis of damaged germ cells or to
      protect germ cells from genotoxic stress. Here, we have correlated data from a
      number of molluscan and other invertebrate sequencing projects to provide a
      framework for understanding p53 signalling pathways in marine bivalve cancer and
      stress biology. These data suggest that (a) the two identified p53 and p63/73
      like proteins in soft shell clam (Mya arenaria), blue mussel (Mytilus edulis) and
      Northern European squid (Loligo forbesi) have identical core sequences and may be
      splice variants of a single gene, while some molluscs and most other
      invertebrates have two or more distinct genes expressing different p53 family
      members; (b) transcriptional activation domains (TADs) in bivalve p53 and p63/73
      like protein sequences are 67-69% conserved with human p53, while those in
      ecdysozoan, cnidarian, placozoan and choanozoan eukaryotes are <=33% conserved;
      (c) the Mdm2 binding site in the transcriptional activation domain is 100%
      conserved in all sequenced bivalve p53 proteins (e.g. Mya, Mytilus, Crassostrea
      and Spisula) but is not present in other non-deuterostome invertebrates; (d) an
      Mdm2 homologue has been cloned for Mytilus trossulus; (e) homologues for both
      human p53 upstream regulatory and transcriptional target genes exist in molluscan
      genomes (missing are ARF, CIP1 and BH3 only proteins) and (f) p53 is demonstrably
      involved in bivalve haemocyte and germinoma cancers. We usually do not know
      enough about the molecular biology of marine invertebrates to address molecular
      mechanisms that characterize particular diseases. Understanding the molecular
      basis of naturally occurring diseases in marine bivalves is a virtually
      unexplored aspect of toxicoproteomics and genomics and related drug discovery.
      Additionally, increases in coastal development and concomitant increases in
      aquatic pollutants have driven interest in developing models appropriate for
      evaluating potential hazardous compounds or conditions found in the aquatic
      environment. Data reviewed in this study are coupled with recent developments in
      our understanding the molecular biology of the marine bivalve p53 superfamily.
      Taken together, they suggest that both structurally and functionally, bivalve p53
      family proteins are the most highly conserved members of this gene superfamily so
      far identified outside of higher vertebrates and invertebrate chordates. Marine
      bivalves provide some of the most relevant and best understood models currently
      available for experimental studies by biomedical and marine environmental
      researchers.

PMID- 21724018
TI  - Stress ecology in fucus: abiotic, biotic and genetic interactions.
AB  - Stress regimes defined as the synchronous or sequential action of abiotic and
      biotic stresses determine the performance and distribution of species. The
      natural patterns of stress to which species are more or less well adapted have
      recently started to shift and alter under the influence of global change. This
      was the motivation to review our knowledge on the stress ecology of a benthic key
      player, the macroalgal genus Fucus. We first provide a comprehensive review of
      the genus as an ecological model including what is currently known about the
      major lineages of Fucus species with respect to hybridization, ecotypic
      differentiation and speciation; as well as life history, population structure and
      geographic distribution. We then review our current understanding of both
      extrinsic (abiotic/biotic) and intrinsic (genetic) stress(es) on Fucus species
      and how they interact with each other. It is concluded that (i) interactive
      stress effects appear to be equally distributed over additive, antagonistic and
      synergistic categories at the level of single experiments, but are predominantly
      additive when averaged over all studies in a meta-analysis of 41 experiments;
      (ii) juvenile and adult responses to stress frequently differ and (iii) several
      species or particular populations of Fucus may be relatively unaffected by
      climate change as a consequence of pre-adapted ecotypes that collectively express
      wide physiological tolerences. Future research on Fucus should (i) include
      additional species, (ii) include marginal populations as models for responses to
      environmental stress; (iii) assess a wider range of stress combinations,
      including their temporal fluctuations; (iv) better differentiate between stress
      sensitivity of juvenile versus adult stages; (v) include a functional genomic
      component in order to better integrate Fucus' ecological and evolutionary
      responses to stress regimes and (vi) utilize a multivariate modelling approach in
      order to develop and understand interaction networks.

PMID- 21724019
TI  - Hydrozoans and the shape of things to come.
AB  - The physiological mechanisms that regulate adaptive plasticity of clonal
      organisms are key to their success in changing environments. Here, we review the
      mechanisms that regulate morphological plasticity of colonial hydrozoans. There
      is a heritable, genetic basis to colony form, but environmentally-induced
      plasticity and self-reinforcing developmental physiology explain much of total
      phenotypic variance. Morphological development of colonial hydrozoans emerges
      from interactions among (1) behaviors which drive gastrovascular transport, (2)
      architecture of the gastrovascular system that determines hydrodynamic
      characteristics of vascular flow, and, (3) gene products that vary in response to
      physiological signals provided by gastrovascular transport. Several morphogenetic
      signaling mechanisms have been identified, including, reactive oxygen species and
      nutrient concentrations in the hydroplasm, and hydromechanical forces associated
      with gastrovascular transport. We present a conceptual model of the interacting
      forces that drive hydrozoan morphological development. Several avenues for future
      research are suggested by the synthesis of information from prior studies of
      hydrozoans. Elucidating the morphogenetic signaling pathways responsive to
      metabolites or hydromechanical forces and the epigenetic effect of vascular
      architecture on colony form may give new insight into the self-maintenance of
      indeterminately growing and continuously developing vascular systems.

PMID- 21724020
TI  - Ultraviolet radiation and echinoderms: past, present and future perspectives.
AB  - There is general consensus that solar ultraviolet radiation (UVR) negatively
      impacts many marine species. Echinoderms are ubiquitous within the marine
      environment, with members of the phyla often long-lived and numerically dominant
      within the benthic macrofauna, consequently the impact of UVR on the population
      dynamics of these organisms will influence marine communities and ecosystems.
      Research to date has shown that exposure of echinoderms to solar UVR can, affect
      reproduction and development, change behaviour, cause numerous biochemical and
      physiological changes and potentially cause increased mutation rates, by causing
      DNA damage. There is also considerable evidence that echinoderms utilise several
      different mechanisms to protect themselves against excessive UVR and subsequent
      UVR-induced damage. However, these protective mechanisms may pose conflicting
      selection pressures on echinoderms, as UVR is an additional stressor in oceans
      subjected to anthropogenic-induced climate change. This review summarises our
      knowledge of the effects of UVR on the Echinodermata. We outline the research
      conducted to date, highlight key studies on UVR that have utilised echinoderms
      and look to the future of UVR research in a rapidly changing ocean.

PMID- 21724021
TI  - The need for asylum.

PMID- 21724022
TI  - A new era for global tuberculosis control?

PMID- 21724023
TI  - Drug advertising in The Lancet.

PMID- 21724026
TI  - Richard Reznick: leading innovator of surgical education.

PMID- 21724027
TI  - Consent in emergency care research.

PMID- 21724028
TI  - Consent in emergency care research.

PMID- 21724029
TI  - Consent in emergency care research.

PMID- 21724030
TI  - Consent in emergency care research.

PMID- 21724031
TI  - Consent in emergency care research.

PMID- 21724032
TI  - Early administration of tranexamic acid in trauma patients.

PMID- 21724035
TI  - Don't forget family planning.

PMID- 21724036
TI  - The importance of climate change to health.

PMID- 21724037
TI  - Pharmaceutical company advertising in The Lancet.

PMID- 21724038
TI  - Late onset autism and anti-NMDA-receptor encephalitis.

PMID- 21724039
TI  - Decreasing multiple drug-resistant organisms.

PMID- 21724040
TI  - Cardiologists' knowledge of the 2005 American Heart Association Resuscitation
      Guidelines: The Athens Study.
AB  - OBJECTIVE: The study objective was to determine cardiologists' theoretic
      knowledge of the 2005 American Heart Association (AHA) resuscitation guidelines.
      METHODS: The questionnaire consisted of demographic questions, resuscitation
      experience questions, a question regarding confidence in resuscitation skills,
      and 20 theoretic knowledge questions. RESULTS: For the theoretic knowledge
      questions, the participants' overall mean score was 9.9 +/- 4.6 (range 3-20).
      Participants who had received advanced cardiac life support (ACLS) training
      scored significantly higher. Furthermore, those who had attended the ACLS course
      in the preceding year scored significantly higher compared with those who had
      attended the ACLS course more than 1 year before the survey (19.1 +/- .6 vs 16.7
      +/- .67, P = .001). Theoretic knowledge of resuscitation did not increase with
      seniority. Furthermore, no correlation was observed between the theoretic
      knowledge scores and participants' self-appraisal of resuscitation knowledge.
      CONCLUSION: Cardiologists have knowledge gaps in the 2005 AHA resuscitation
      guidelines. Resuscitation knowledge decay 1 year after the course is evident.

PMID- 21724041
TI  - Effects of humor and laughter on psychological functioning, quality of life,
      health status, and pulmonary functioning among patients with chronic obstructive
      pulmonary disease: a preliminary investigation.
AB  - OBJECTIVE: Previous research indicates the beneficial effects of humor among
      healthy adults. Little is known about the physical and psychological effects of
      sense of humor and laughter among patients with chronic obstructive pulmonary
      disease (COPD). METHODS: Patients with COPD (n = 46; mean age +/- SD, 66.9 +/-
      9.9 years) completed assessments of sense of humor, depression, anxiety, quality
      of life, and recent illness. A subset of patients (n = 22) completed a laughter
      induction study and were randomly assigned to view either a humorous or a neutral
      video. Pulmonary function, mood state, and dyspnea were assessed before and after
      the video. RESULTS: Sense of humor was associated with fewer symptoms of
      depression and anxiety and an enhanced quality of life. However, the induction of
      laughter led to lung hyperinflation. CONCLUSION: Sense of humor among patients
      with COPD is associated with positive psychological functioning and enhanced
      quality of life, but laughing aloud may cause acute deterioration in pulmonary
      function secondary to worsened hyperinflation.

PMID- 21724042
TI  - Prinzmetal's angina in a patient with angiosarcoma of the right cardiac chambers.
AB  - Variant (Prinzmetal's) angina pectoris is a clinical syndrome characterized by
      the presence of angina at rest, coinciding with a transient ST-segment elevation.
      This syndrome is often caused by vasospasm, either on a normal coronary artery or
      at the site of a coronary atherosclerotic stenosis. We describe a classic case of
      variant angina associated with an angiosarcoma of the right heart chambers.

PMID- 21724043
TI  - Unusually severe varicella zoster (VZV) virus viral (aseptic) meningitis in an
      unimmunized, immunocompetent host with chickenpox.
AB  - Chickenpox is caused by the varicella zoster virus (VZV) and may be more severe
      in adults than in children. Central nervous system (CNS) manifestations of
      chickenpox and VZV are uncommon, for example, encephalitis and cerebellar ataxis.
      Viral (aseptic) meningitis is a rare CNS complication of VZV. The cerebrospinal
      fluid (CSF) profile in VZV viral (aseptic) meningitis is indistinguishable from
      other causes of viral meningitis. The clue to most of the diagnoses of VZV
      aseptic meningitis is based on the temporal relationship between antecedent or
      concomitant chickenpox. Chickenpox is a clinical diagnosis based on the
      appearance and distribution of the rash. The rash of chickenpox is
      vesicular/pruritic and typically appears in crops over 3 successive days. VZV
      vesicles are fragile, superficial, and surrounded by a erythematous halo. Common
      nonspecific laboratory findings in chickenpox include leukopenia,
      thrombocytopenia, and elevated serum transaminases (serum glutamate-oxaloacetate
      transaminase/serum glutamate-pyruvate transaminase). The erythrocyte
      sedimentation rate (ESR) is not highly elevated in chickenpox. In VZV aseptic
      meningitis, the CSF shows a lymphocytic pleocytosis with normal protein, glucose,
      and lactic acid levels. CSF red blood cells are not a feature of VZV meningitis.
      We present the case of a healthy unimmunized adult who was hospitalized with
      chickenpox complicated by VZV aseptic meningitis with an unusually severe
      headache and nuchal rigidity that occurred during hospitalization.

PMID- 21724044
TI  - Retinopathy of prematurity in the time of bevacizumab: incorporating the BEAT-ROP
      results into clinical practice.

PMID- 21724045
TI  - Novel glaucoma procedures: a report by the American Academy of Ophthalmology.
AB  - OBJECTIVE: To review the published literature and summarize clinically relevant
      information about novel, or emerging, surgical techniques for the treatment of
      open-angle glaucoma and to describe the devices and procedures in proper context
      of the appropriate patient population, theoretic effects, advantages, and
      disadvantages. DESIGN: Devices and procedures that have US Food and Drug
      Administration clearance or are currently in phase III clinical trials in the
      United States are included: the Fugo blade (Medisurg Ltd., Norristown, PA), Ex
      PRESS mini glaucoma shunt (Alcon, Inc., Hunenberg, Switzerland), SOLX Gold Shunt
      (SOLX Ltd., Boston, MA), excimer laser trabeculotomy (AIDA, Glautec AG, Nurnberg,
      Germany), canaloplasty (iScience Interventional Corp., Menlo Park, CA),
      trabeculotomy by internal approach (Trabectome, NeoMedix, Inc., Tustin, CA), and
      trabecular micro-bypass stent (iStent, Glaukos Corporation, Laguna Hills, CA).
      METHODS: Literature searches of the PubMed and the Cochrane Library databases
      were conducted up to October 2009 with no date or language restrictions. MAIN
      OUTCOME MEASURES: These searches retrieved 192 citations, of which 23 were deemed
      topically relevant and rated for quality of evidence by the panel methodologist.
      All studies but one, which was rated as level II evidence, were rated as level
      III evidence. RESULTS: All of the devices studied showed a statistically
      significant reduction in intraocular pressure and, in some cases, glaucoma
      medication use. The success and failure definitions varied among studies, as did
      the calculated rates. Various types and rates of complications were reported
      depending on the surgical technique. On the basis of the review of the literature
      and mechanism of action, the authors also summarized theoretic advantages and
      disadvantages of each surgery. CONCLUSIONS: The novel glaucoma surgeries studied
      all show some promise as alternative treatments to lower intraocular pressure in
      the treatment of open-angle glaucoma. It is not possible to conclude whether
      these novel procedures are superior, equal to, or inferior to surgery such as
      trabeculectomy or to one another. The studies provide the basis for future
      comparative or randomized trials of existing glaucoma surgical techniques and
      other novel procedures.

PMID- 21724046
TI  - Diplopia and quality of life.

PMID- 21724047
TI  - Nepafenac for epiretinal membrane surgery.

PMID- 21724048
TI  - Ptosis following laser treatment.

PMID- 21724049
TI  - Pancreatic cancer metastasis to choroid.

PMID- 21724050
TI  - Definition of ACD.

PMID- 21724051
TI  - INF alpha2b for ocular squamous neoplasia.

PMID- 21724054
TI  - Keratoprosthesis in china.

PMID- 21724056
TI  - Transscleral diffusion of triamcinolone.

PMID- 21724057
TI  - Chemosensitivity of medulloepithelioma.

PMID- 21724059
TI  - Leber's hereditary optic neuropathy.

PMID- 21724060
TI  - Consecutive exotropia.

PMID- 21724062
TI  - Practice finances.

PMID- 21724064
TI  - Special Issue: progress in graphonomics: a perceptual motor skill perspective.

PMID- 21724065
TI  - Paths to the making of an academic clinical investigator--part 2.

PMID- 21724066
TI  - Cervical vertebral column morphology related to craniofacial morphology and head
      posture in preorthodontic children with Class II malocclusion and horizontal
      maxillary overjet.
AB  - INTRODUCTION: In preorthodontic children with Class II malocclusion and
      horizontal maxillary overjet, cervical column morphology was examined and related
      to craniofacial morphology and head posture for the first time. METHODS: Two
      hundred thirteen children (aged 7-15 years) with a horizontal maxillary overjet
      of more than 6 mm were divided into 2 groups of skeletal and dentoalveolar
      overjets. The skeletal overjet group comprised 99 patients (43 girls, 56 boys).
      The dentoalveolar overjet group comprised 114 subjects (58 girls, 56 boys).
      Visual assessments of the cervical column and measurements of craniofacial
      morphology and head posture were made on profile radiographs. RESULTS: Deviations
      in the cervical vertebral column morphology occurred significantly more often in
      the skeletal overjet group (28%) compared with the dentoalveolar overjet group
      (17%) (P <0.05). Fusion anomalies were associated with a large sagittal jaw
      relationship, retrognathia of the jaws, large inclination of the jaws, and
      extended head posture (P <0.05 and 0.01, respectively). Furthermore, a partial
      cleft was significantly associated with a large cranial base angle (P <0.01).
      CONCLUSIONS: New associations were found between cervical column morphology,
      craniofacial morphology, and head posture in preorthodontic children with
      horizontal maxillary overjet. These findings are considered important for
      diagnostics and thus for a more accurate treatment plan of these patients.

PMID- 21724067
TI  - White-spot lesions during multibracket appliance treatment: A challenge for
      clinical excellence.
AB  - INTRODUCTION: White-spot lesions (WSL) are one of the most undesired side effects
      of multibracket appliance treatment (MB). The aim of this study was to
      investigate the incidence and further course of WSL during and after MB. METHODS:
      Four hundred patients (168 boys, 232 girls) meeting the inclusion criteria--all
      maxillary front teeth fully erupted and visible before treatment, no fillings or
      structural abnormalities, MB duration of at least 1 year, and retention period of
      at least 1 year--were selected. The patients' average age was 13.7 years (SD,
      3.5), and the average MB time was 1.9 years (SD, 3.6). All patients received
      standardized general prophylactic instructions. A modification of the WSL index
      was used to evaluate the 4 maxillary front teeth on introral photos before and
      after treatment, and after retention. RESULTS: Before treatment, 32.3% of the
      patients had WSL. After MB, 73.5% of the patients presented WSL. The incidence of
      WSL during MB was 60.9% of the patients. After treatment, most patients (63.3%)
      had mild lesions, but the remaining were affected severely with (26.9%) and
      without (9.9%) cavitations. Only 26% of the patients were free of WSL all the
      time. After the retention phase, most (57.1%) of the WSL patients after treatment
      showed improvement, 26% remained unchanged, and 16.7% deteriorated. Male WSL
      patients tended to show more severe WSL than did the girls. There was a tendency
      for increased WSL development during the adolescent years compared with the
      preadolescent and postadolescent age groups. CONCLUSIONS: With only standardized
      general prophylactic measures, new WSL developing on the maxillary front teeth
      during MB remain a frequent undesired side effect, affecting 60.9% of patients
      and counteracting our efforts for clinical excellence.

PMID- 21724068
TI  - Cone-beam computed tomography to detect erosions of the temporomandibular joint:
      Effect of field of view and voxel size on diagnostic efficacy and effective dose.
AB  - INTRODUCTION: In this study, we examined the influence of field of view (FOV) and
      voxel size on the diagnostic efficacy of cone-beam computed tomography (CBCT)
      scans to detect erosions in the temporomandibular joint (TMJ). METHODS: The
      sample consisted of 16 TMJs containing natural or artificially created erosions
      and 16 normal TMJs. CBCT scans were obtained with 3 imaging protocols differing
      in the FOV and the size of the reconstructed voxels. Two oral and maxillofacial
      radiologists scored the scans for the presence or absence of erosions. Diagnostic
      efficacies of the 3 imaging protocols were compared by using receiver operating
      curve analysis. For each TMJ imaging protocol, we used thermoluminescent
      dosimetry chips to measure the absorbed dose at specific organ and tissue sites.
      Effective doses for each examination were calculated. RESULTS: Areas under the
      receiver operating characteristic curves were 0.77 +/- 0.05 for the 6-in FOV,
      0.70 +/- 0.08 for the 9-in FOV, and 0.66 +/- 0.05 for the 12-in FOV. The
      diagnostic efficacy of the 6-in FOV, determined by the area under the curve, was
      significantly higher than that of the 12-in FOV (P <=0.05). Effective doses for
      bilateral TMJ evaluation were 558 MUSv for the 6-in FOV, 548 MUSv for the 9-in
      FOV, and 916 MUSv for the 12-in FOV. CONCLUSIONS: The diagnostic efficacy of CBCT
      scans for the evaluation of erosive changes in the TMJ is highest for the 6-in
      FOV and lowest for the 12-in FOV.

PMID- 21724069
TI  - Effects of bisphosphonates on sutural bone formation and relapse: A histologic
      and immunohistochemical study.
AB  - INTRODUCTION: The aim of this experimental study was to evaluate the effects of
      systemically applied zoledronic acid on bone regeneration in response to
      expansion of the sagittal suture and relapse in rats. METHODS: Thirty-six male
      Wistar rats were divided into 3 groups. In the first and second groups, saline
      solution was given subcutaneously after expansion, and the retention periods
      lasted 14 and 7 days, respectively. In the third group, 0.1 mg of zoledronic acid
      was diluted with saline solution and given subcutaneously after expansion; the
      retention period lasted for 7 days. Expansion and relapse amounts were measured
      by using computed tomography. After the retention period, 6 rats from each group
      were killed for histologic and immunohistochemical assessments. The other 6 rats
      from each group were used for observation of the relapse. RESULTS: The histologic
      evaluation showed that, in groups 1 and 2, the numbers of osteoblasts were less
      than observed in group 3. When scores of staining intensity were compared,
      immunoreactivities were statistically significantly increased in group 3 compared
      with groups 2 and 1. Statistically significant differences were found when the
      relapse percentages were compared between the groups (P <0.05). The smallest
      relapse occurred in group 3. CONCLUSIONS: Zoledronic acid has positive effects on
      bone formation in the sagittal suture in response to expansion and decreases the
      relapse ratio after expansion in rats.

PMID- 21724070
TI  - Spectrophotometric evaluation of color alterations with a new dental bleaching
      product in patients wearing orthodontic appliances.
AB  - INTRODUCTION: Our objective was to assess the effectiveness of a new bleaching
      agent (8% hydrogen peroxide) used in patients wearing fixed orthodontic
      appliances. METHODS: Six anterior maxillary teeth of 40 patients aged 18 to 40
      years were assessed. The patients were divided into 2 groups (20 in each group):
      in group A, the patients used the bleaching agent during orthodontic treatment;
      in group B, the patients used the bleaching agent after orthodontic treatment.
      For each group, a record of the initial tooth shade was taken with a polyvinyl
      siloxane matrix and a spectrophotometer. The groups had bleaching treatments with
      an 8% hydrogen peroxide product (Opalescence Treswhite Ortho, Ultradent, Opal
      Orthodontics, South Jordan, Utah) for 10 days in 45-minute sessions. For group A,
      the treatment was performed 10 days before finishing orthodontic treatment; at
      the end of the treatment, a new tooth shade record was taken with the polyvinyl
      siloxane matrix and a spectrophotometer. The subjects in group B had the same
      bleaching protocol after their brackets were removed. RESULTS: It was observed
      that, for the group without brackets, the color alteration ranged from 3 to 12
      (mean, 8; median, 8.3); for the group with brackets, the range was between 4 and
      13 (mean, 9; median, 8.5), indicating significant tooth bleaching in both groups
      with and without brackets (P >0.05). CONCLUSIONS: Opalescence Treswhite Ortho was
      shown to be an efficient bleaching agent in patients wearing fixed orthodontic
      appliances.

PMID- 21724071
TI  - Physical properties of root cementum: Part 19. Comparison of the amounts of root
      resorption between the right and left first premolars after application of
      buccally directed heavy orthodontic tipping forces.
AB  - INTRODUCTION: Previous studies have used the right and left sides of the same jaw
      to compare different force levels, types of movement, and durations of forces.
      However, the amounts of root resorption have not been compared between the right
      and left sides after applying the same amount of force. The aims of the study
      were to quantitatively compare the volumes of the root resorption lacunae between
      the right and left first premolars to determine whether 1 side can serve as a
      control to the other and to compare the volumes of root resorption lacunae of the
      first premolars between the maxilla and the mandible. METHODS: Forty-four first
      premolars, orthodontically indicated for extraction from 11 patients (left and
      right maxillary and mandibular first premolars from each) were moved buccally by
      using beta-titanium-molybdenum alloy 0.017 * 0.025-in cantilever springs with
      continuous heavy (225 g) force. After the experimental period, the teeth were
      extracted under a strict protocol to prevent root cementum damage and then
      analyzed by using a microcomputed tomography scan x-ray system (1172; SkyScan,
      Aartselaar, Belgium) and specially designed software (Convex Hull 2D, University
      of Sydney, Sydney, Australia) for direct volumetric measurements. RESULTS: There
      were no statistically significant differences in the mean cube root volumes of
      root resorption craters between the right and left sides (P = 0.18) or between
      the maxillary and mandibular jaws (P = 0.10). There was also no statistical
      significance for the interception (P = 0.41), which indicated that the jaw and
      the side had independent effects. CONCLUSIONS: The amount of root resorption on
      the left and right sides of the jaw were similar in both the maxilla and the
      mandible. Therefore, for future root resorption studies, it is justifiable to use
      the split-mouth technique so that teeth from 1 side of the jaw can serve as the
      controls.

PMID- 21724072
TI  - Analysis of genetic polymorphisms in skeletal Class I crowding.
AB  - INTRODUCTION: Dental crowding is a problem for both adolescents and adults in
      modern society. The purpose of this research was to identify single nucleotide
      polymorphisms (SNPs) responsible for crowding in subjects with skeletal Class I
      relationships. METHODS: The case subjects consisted of healthy Chinese people
      living in Hong Kong with skeletal Class I relationships and at least 5 mm of
      crowding in either arch. The control subjects met the same requirements but
      lacked crowding or spacing. SNP genotyping was performed on the MassARRAY
      platform. The chi-square test was used to compare genotype and allele type
      distributions between the case and the control groups. Logistic regression was
      used to calculate odds ratios with 95% confidence intervals, and the effects of
      age and sex for each SNP. Analyses of linkage disequilibrium and haplotype
      associations between SNPs were performed with software. RESULTS: Five SNPs were
      found to be significantly different in genotype or allele type distributions. SNP
      rs372024 was significantly associated with crowding (P = 0.004). Two SNPs,
      rs3764746 and rs3795170, on the EDA gene were found to be associated marginally.
      SNPs rs1005464 and rs15705 also exhibited marginal association with crowding. The
      effects of associated SNPs remained significant after adjustments for age and sex
      factors. CONCLUSIONS: This study suggests an association for the genes EDA and
      XEDAR in dental crowding in the Hong Kong Chinese population.

PMID- 21724073
TI  - How good are you?

PMID- 21724074
TI  - Heuristic reasoning and cognitive biases.

PMID- 21724075
TI  - Problematic sample in the study of interception of palatally displaced canines.

PMID- 21724077
TI  - Study clubs.

PMID- 21724078
TI  - Ethics in orthodontics. Communication in the face of conflict.

PMID- 21724080
TI  - Evaluation and management of asymptomatic third molars: Lack of symptoms does not
      equate to lack of pathology.

PMID- 21724081
TI  - Evaluation and management of asymptomatic third molars: Watchful monitoring is a
      low-risk alternative to extraction.

PMID- 21724082
TI  - Temporomandibular joint and normal occlusion: Is there anything singular about
      it? A computed tomographic evaluation.
AB  - INTRODUCTION: The purpose of this study was to investigate the condyle-fossa
      relationship, the position of the condyles in their respective mandibular fossae,
      and the dimensional and positional symmetries between the right and left condyles
      in a sample with normal occlusion. METHODS: Thirty subjects from 15 to 32 years
      of age with normal occlusion had computed tomography scans of their
      temporomandibular joints. The images obtained from the axial slices were
      evaluated for possible asymmetries in size and position between the condylar
      processes. The images obtained from the sagittal slices were used to assess the
      depth of the mandibular fossa, the condyle-fossa relationship, and the
      centralization of the condyles in their respective mandibular fossae. Paired
      Student t tests were applied, and Pearson product moment correlations were
      determined after measurements on both sides were obtained. RESULTS: The largest
      mediolateral diameter of the mandibular condylar processes (P = 0.022) and the
      posterior joint spaces (P = 0.048) showed statistically significant differences
      between the right and left sides. Statistically significant (P <0.05) anterior
      positioning of the condyles (noncentralized position) was observed. CONCLUSIONS:
      No singular characteristic in the temporomandibular joints of the normal
      occlusion group was verified. The largest mediolateral diameter of the mandibular
      condylar processes and the posterior joint spaces showed statistically
      significant differences between the right and left sides. Evaluation of the
      position of the condyles in their respective mandibular fossae showed
      noncentralized positioning for the right and left sides.

PMID- 21724083
TI  - Galvanic corrosion between various combinations of orthodontic brackets and
      archwires.
AB  - INTRODUCTION: The purpose of this study was to compare galvanic currents
      generated by different combinations of commonly used brackets and archwires.
      METHODS: As-received stainless steel, nickel-titanium, and beta-titanium wires
      were coupled to stainless steel and titanium brackets in an artificial saliva
      medium. The galvanic current and amount of charge transferred for each pair were
      monitored with a zero resistance ammeter for 10 hours. RESULTS: Two-way analysis
      of variance (ANOVA) showed a significant difference in charge and galvanic
      currents when factored for type of bracket (P <0.001), but no significant
      difference between them when factored by type of wire (P >0.05). Specifically, a
      brazed stainless steel bracket was significantly greater in charge transferred
      and 10-hour galvanic current than metal injection molded stainless steel and
      titanium brackets (P <0.001), which were not different from each other (P >0.05).
      CONCLUSIONS: The method of bracket manufacturing might be of equal or more
      relevance to galvanic corrosion susceptibility than bracket composition.

PMID- 21724084
TI  - Mandibular second molar impaction. Part I: Genetic traits and characteristics.
AB  - INTRODUCTION: Detection of mandibular second molar (MM2) impaction is imperative
      for orthodontic diagnosis and treatment. In this study, we examined a possible
      genetic trait in MM2 impaction in 2 populations and defined distinctive
      characteristics. METHODS: Initial panoramic radiographs of patients of Israeli (n
      = 3500) and Chinese-American (n = 3000) origin, aged 11 to 15 years, were
      examined. Twelve distinctive characteristics were compared between the unilateral
      impacted and the nonimpacted sides. RESULTS: A total of 120 subjects with MM2
      impaction were found (1.8%). The Chinese-American population had a higher
      prevalence (n = 71, 2.3%) of MM2 impaction compared with the Israeli population
      (n = 49, 1.4%; P = 0.004). For the subjects with MM2 impaction, the Israelis had
      significantly (P = 0.039) fewer bilateral impactions (27%) than did the Chinese
      Americans (45%). Mesially inclined impacted MM2s were more common (88% and 89%)
      in the Israeli and Chinese-American populations, respectively. The unilateral
      impacted side demonstrated reductions in the distance between the mandibular
      first molar and the ramus (P <0.001), the length of the mesial root of the MM2 (P
      <0.001), and the height between the MM2 and the mandibular third molar, and
      increases in the angulations of the MM2 (P <0.001) and the mandibular third molar
      (P <0.003). CONCLUSIONS: An autosomal genetic trait is present in MM2 impaction
      with greater penetrance in the Chinese-American population. Within developmental
      impediments, the deficient mesial root length of the MM2 is the primary impaction
      factor.

PMID- 21724085
TI  - Chincup treatment modifies the mandibular shape in children with prognathism.
AB  - INTRODUCTION: Although chincups are the preferred treatment for growing children
      with mandibular prognathism, the mechanism by which chincups improve this
      condition remains unclear. The aim of this study was to use geometric
      morphometrics to evaluate changes in the shape of the mandible of prognathic
      children treated with a chincup. METHODS: Geometric morphometrics were used to
      evaluate the short-term mandibular shape changes in 50 prognathic children
      treated with chincups compared with 40 untreated matched controls. Twenty-one 2
      dimensional mandibular landmarks from cephalograms taken before and after 36
      months of treatment or observation were analyzed by Procrustes superimposition
      and thin plate spline. RESULTS: Permutation tests of the treated patients showed
      highly significant differences in the mandibular shapes before and after
      treatment, and compared with the control group after the observation period. The
      thin plate spline grid deformations indicated more rectangular mandibular
      configuration, forward condyle orientation, condyle neck compression, gonial area
      compression, and symphysis narrowing. CONCLUSIONS: Early chincup treatment widely
      modifies the mandibular shape of prognathic children to improve Class III
      malocclusion.

PMID- 21724086
TI  - Effects of force magnitude on relapse: An experimental study in rabbits.
AB  - INTRODUCTION: The aims of this study were to investigate the effects of 2 force
      levels on the amount of relapse and to determine whether there is a relationship
      between the rates of tooth movement and relapse. METHODS: Approximately 20-g
      (group I) and 60-g (group II) forces were applied to the maxillary central
      incisors of 25 young adult (14 weeks of age) New Zealand female rabbits. Active
      tooth movement lasted 20 days. Then, the appliances were removed, and the
      incisors were released. The distance between the incisors was measured daily from
      the midlevels of the crowns by using a digital caliper during the active phase of
      tooth movement for 20 days, and then relapse was measured at the same level for
      37 days. Analysis of variance and the Bonferroni multiple range test were used
      for statistical analyses. RESULTS: After active tooth movement, the mean total
      opening amounts were 3.98 +/- 0.59 mm in group I and 4.82 +/- 0.82 mm in group
      II, and the mean difference was approximately 0.8 mm. A rapid relapse was
      observed on the initial days in both groups, and its rate decreased with time.
      Significant relapse was observed in the first 5 and 8 days of the experiment in
      20-g and 60-g force groups, respectively. The relapse in group II was
      significantly greater than in group I only on the first day of experiment.
      Statistically significant correlations were found between total tooth movement
      and relapse (R = 0.896, P <0.001). CONCLUSIONS: These results showed a close
      relationship between the amount of relapse and orthodontic force magnitude.
      Greater relapse occurred during the initial days after appliance removal, and
      this indicates that retention appliances are needed immediately after the removal
      of orthodontic appliances.

PMID- 21724087
TI  - Evaluation of home disinfection protocols for acrylic baseplates of removable
      orthodontic appliances: A randomized clinical investigation.
AB  - INTRODUCTION: In this randomized clinical trial, we investigated, using the
      microbial culture technique and scanning electron microscopy, the contamination
      of acrylic baseplates of removable orthodontic appliances by mutans streptococci
      (MS) and evaluated the efficacy of different home disinfection protocols with a
      0.12% chlorhexidine gluconate spray (Periogard, Colgate-Palmolive, Sao Bernardo
      do Campo, Brazil). METHODS: Fifteen dental students were randomly enrolled in a 3
      stage changeover system with a 1-week interval between each stage. The acrylic
      baseplates were worn full time except at meals to simulate the routine use of
      removable appliances under clinical conditions. Three 1-week home disinfection
      protocols were tested in all stages by a different group of students: protocol I,
      toothbrushing + baseplate brushing + sterile tap water spraying once a day;
      protocol II, toothbrushing + baseplate brushing + Periogard spraying on the
      seventh day after appliance placement; and protocol III, toothbrushing +
      baseplate brushing + Periogard spraying on the fourth and seventh days after
      appliance placement. After the first week, the volunteers received new
      baseplates, toothbrushes, and dentifrices, and the regimens were repeated 2 more
      times. At the end of each week, the baseplates had a randomized disinfection
      protocol and were sent for microbiologic analysis. A scanning electron microscope
      was used to examine 3 acrylic baseplates representing each home protocol. The
      Friedman test (alpha = 0.05) compared the home protocols for the formation of MS
      colonies or biofilms on the acrylic surfaces. RESULTS: MS colonies or biofilms
      were found on all acrylic baseplates after protocol I. Protocols II and III
      reduced significantly (P <0.05) the number of MS colonies and biofilms on the
      acrylic surfaces. No significant difference (P >0.05) was observed between
      protocols II and III. The scanning electron microscope analysis confirmed the
      results of the microbiologic cultures. CONCLUSIONS: Disinfection of baseplates of
      removable orthodontic appliances by using 0.12% chlorhexidine spray once or twice
      a week reduced the contamination by MS on the acrylic surface in vivo.

PMID- 21724088
TI  - Clinical, microbiologic, and immunologic factors of orthodontic treatment-induced
      gingival enlargement.
AB  - INTRODUCTION: The aim of this study was to investigate the microbiologic and
      immunologic factors related to orthodontic treatment-induced gingival enlargement
      (GE). METHODS: Our study included 12 patients with GE undergoing fixed
      orthodontic treatment and 12 periodontally healthy controls. At baseline,
      periodontal variables, subgingival plaque samples, and gingival crevicular fluid
      (GCF) samples were taken from 2 preselected sites in both the GE and the control
      groups. The levels of Porphyromonas gingivalis, Aggregatibacter
      actinomycetemcomitans, Prevotella intermedia, Treponema denticola and Tannerella
      forsythia were determined by real-time polymerase chain reaction. GCF interleukin
      (IL)-1beta and transforming growth factor-beta 1 (TGF-beta1) were detected by
      enzyme-linked immunosorbent assay (Invitrogen, Camarillo, Calif). Periodontal
      therapy was given to the GE group, and all parameters were reassessed after 4
      weeks. RESULTS: At baseline, the GE group showed higher prevalences of the 5
      periodontal pathogens than did the control group (P <0.05). IL-1beta and TGF
      beta1 levels at the GE sites were also significantly higher than those at the
      control sites (P <0.05). Four weeks after periodontal therapy, the GE group
      showed significant improvements in the clinical parameters associated with
      significant reductions of P gingivalis, A actinomycetemcomitans, and T denticola.
      The levels of IL-1beta decreased significantly compared with the baseline (P
      <0.05), whereas there was no significant change in TGF-beta1 levels (P >0.05).
      CONCLUSIONS: Periodontal pathogens might have a relationship with the initiation
      and development of orthodontic treatment-induced GE. Inflammatory cytokines (IL
      1beta and TGF-beta1) can also be considered as contributing factors.

PMID- 21724089
TI  - Comparisons of nanoindentation, 3-point bending, and tension tests for
      orthodontic wires.
AB  - INTRODUCTION: The purposes of this study were to obtain information about
      mechanical properties with the nanoindentation test for representative wire
      alloys and compare the results with conventional mechanical tests. METHODS:
      Archwires having 0.016 * 0.022-in cross sections were obtained of 1 stainless
      steel, 1 cobalt-chromium-nickel, 1 beta-titanium alloy, and 2 nickel-titanium
      products. Specimens of as-received wires were subjected to nanoindentation
      testing along the external surfaces and over polished cross sections to obtain
      values of hardness and elastic modulus. Other specimens of as-received wires were
      subjected to Vickers hardness, 3-point bending, and tension tests. All testing
      was performed at 25 degrees C. RESULTS: Differences were found in hardness and
      elastic modulus obtained with the nanoindentation test at the external and cross
      sectioned surfaces and with the conventional mechanical-property tests.
      Mechanical properties obtained with the nanoindentation test generally varied
      with indentation depth. CONCLUSIONS: The 3 testing methods did not yield
      identical values of hardness and elastic modulus, although the order among the 5
      wire products was the same. Variations in results for the nanoindentation and
      conventional mechanical property tests can be attributed to the different
      material volumes sampled, different work-hardening levels, and an oxide layer on
      the wire surface.

PMID- 21724090
TI  - Factors controlling anterior torque during C-implant-dependent en-masse
      retraction without posterior appliances.
AB  - INTRODUCTION: Our objective was to evaluate the factors that affect effective
      torque control during en-masse incisor and canine retraction when using partially
      osseointegrated C-implants (Cimplant, Seoul, Korea) as the exclusive source of
      anchorage without posterior bonded or banded appliances. METHODS: Base models
      were constructed from a dental study model. No brackets or bands were placed on
      the maxillary posterior dentition during retraction. The working archwire was
      modeled by using a 3-dimensional beam element (ANSYS beam 4, Swanson Analysis
      System, Canonsburg, Pa) with a cross section of 0.016 * 0.022-in stainless steel.
      Different heights of anterior retraction hooks and different degrees of gable
      bends were applied to the working utility archwire that was placed into the 0.8
      mm diameter hole of the C-implant to generate anterior torque on the anterior
      segment of the teeth. The amount of tooth displacement after finite element
      analysis was exaggerated 70 times and compared with tooth-axis graphs of the
      central and lateral incisors and the canine. RESULTS: The height of the anterior
      retraction hook and the degree of the gable bend had a combined effect on the
      labial crown torque applied to the incisors during en-masse retraction. By using
      30 degrees  gable bends and the longest hook, lingual root movement of the 6
      anterior teeth occurred. By using 20 degrees  gable bends, the 6 anterior teeth
      showed a translation tendency during retraction. CONCLUSIONS: Three-dimensional
      en-masse retraction of the 6 anterior teeth can be accomplished by using
      partially osseointegrated C-implants as the only source of anchorage, gable
      bends, and a long retraction hook (biocreative therapy type I technique).

PMID- 21724091
TI  - Maxillary palatal canine impaction displacement in subjects with congenitally
      missing maxillary lateral incisors.
AB  - INTRODUCTION: The aims of this research were to study the prevalence of palatally
      displaced maxillary canines (PDCs) in subjects with congenitally missing
      maxillary lateral incisor (MxI2) teeth and to assess the dental and occlusal
      features associated with this displacement in these subjects. METHODS: The
      material for this study consisted of the pretreatment orthodontic casts of 246
      subjects (78 male, 168 female) with missing MxI2 teeth. These were divided into 2
      groups: subjects with PDC (displacement group) and subjects with no PDC
      (nondisplacement group). A nondisplacement comparison group was selected by
      matching the displacement group according to age, sex, type of malocclusion, and
      unilateral or bilateral absence of the MxI2 teeth. RESULTS: Of 246 subjects, 31
      (12.6%) were found to have PDC. Sex distribution and type of congenital absence
      of MxI2 teeth were not different in the displacement and the nondisplacement
      groups. There was no significant difference between the dental and occlusal
      features in the displacement and the comparison groups. CONCLUSIONS: There was a
      strong association between PDC and missing MxI2; this supports the guidance
      theory. In subjects with MxI2 agenesis, no other dental or occlusal features were
      found to play a role in PDC.

PMID- 21724092
TI  - Method to classify dental arch forms.
AB  - INTRODUCTION: The aim of this study was to propose a method to classify dental
      arch forms of subjects with normal occlusion into several types that can ensure
      both goodness of fit and clinical application. METHODS: We selected 306 subjects
      with normal occlusion from 15,836 young adults, recorded 14 reference points that
      defined the distance between 2 arch forms as the area between 2 arches, and then
      classified the dental arch forms by using the partitioning around medoids
      clustering and silhouette method. We measured tooth size, arch width, basal arch
      width, arch depth, mesiodistal angulations, and buccolingual inclinations.
      RESULTS: We identified 3 types of arch forms, and cross-classification of the
      maxillary by mandibular arch forms showed a more frequent distribution in the
      diagonal elements than in the off-diagonal elements. The 3 arch forms showed
      differences in tooth size, arch width, basal arch width, and inclination of the
      posterior teeth. CONCLUSIONS: By defining area discrepancies as distance measures
      and applying them to the cluster method by using medoids, the dental arch form
      can be classified keeping control for the extremes without bias. It is hoped that
      this method will have possible clinical applications in determining the shape and
      number of preformed orthodontic arch forms.

PMID- 21724093
TI  - Adult Class II Division 1 patient with severe gummy smile treated with temporary
      anchorage devices.
AB  - A 23-year-old Mongolian woman came for a consultation with chief complaints of
      protrusive lips and a gummy smile. The clinical examination showed a convex
      profile, a protrusive maxilla, excessively proclined and extruded maxillary
      incisors, and a Class II Division 1 malocclusion. Temporary anchorage devices
      (TADs) in the posterior dental region were used as anchorage for the retraction
      and intrusion of her maxillary anterior teeth. Those appliances, combined with a
      compensatory curved maxillary archwire, eliminated the severe gummy smile and the
      protrusive profile, and corrected the molar relationship from Class II to Class
      I. With no extra temporary anchorage devices in the anterior region for
      intrusion, the treatment was workable and simple. The patient received a
      satisfactory occlusion and an attractive smile.

PMID- 21724094
TI  - Nonsurgical treatment of an adult patient with bilateral posterior crossbite.
AB  - A woman with an Angle Class III malocclusion and bilateral posterior crossbites
      complaining of difficulty in chewing was treated orthodontically without surgery.
      The treatment comprised asymmetric extractions, a removable mandibular lingual
      arch constriction appliance to narrow the mandibular arch, and a standard
      edgewise appliance to align the teeth. Pretreatment, posttreatment, and 1-year
      follow-up records are shown. With this treatment strategy of constricting the
      mandibular arch by using a combination of removable and fixed orthodontic
      appliances, we achieved a good result with optimal occlusion.

PMID- 21724095
TI  - Spring-loaded bite-blocks for early correction of skeletal open bite associated
      with thumb sucking.
AB  - Skeletal open-bite malocclusion is frequently discussed in orthodontics.
      Diagnosis, treatment, and retention can be difficult because this malocclusion
      has numerous correlated etiologic factors. The earlier this malocclusion is
      corrected, the better the prognosis will be, especially when the problem is
      skeletal. This article presents a patient with a skeletal open bite and a thumb
      sucking habit who was treated in the mixed dentition with an orthodontic
      appliance that included an acrylic occlusal splint along with spring-loaded
      blocks to guide the vertical force against the posterior teeth and the alveolar
      process. The usefulness of the appliance as a habit-breaking therapy is also
      highlighted.

PMID- 21724096
TI  - Failure after closed traction of an unerupted maxillary permanent canine:
      Diagnosis and treatment planning.
AB  - This report describes the treatment of a 13-year-old girl with unerupted
      maxillary permanent canines. It illustrates how recognizing an unexpected problem
      influenced the decision-making process. Despite 6 months of closed-eruption
      traction, the left canine had not erupted. However, the neighboring teeth were
      intruded, suggesting a diagnosis of canine ankylosis. When the site was
      surgically reopened, the wire chain used for the orthodontic traction appeared to
      be osseointegrated. It was renewed, and traction was applied for another 16
      months, and the tooth was successfully brought into the arch. Bone tissue passing
      through the chain might have prevented forced eruption. In young patients with
      unerupted maxillary permanent canines, failure of closed traction can be
      attributed to ankylosis, and this accounts for tooth extraction as the treatment
      of choice. However, this clinical report suggests that additional measures might
      be warranted before the definitive diagnosis of ankylosis can be made and the
      tooth extracted.

PMID- 21724097
TI  - In-office distance learning for practitioners.
AB  - INTRODUCTION: Distance learning studies involving orthodontic residents have
      shown that, although residents prefer being live and interactive with an
      instructor, they learn almost as much from watching a recorded interactive
      seminar followed by a live discussion. Our objective in this study was to test
      the acceptability and perceived effectiveness of using recorded interactive
      seminars and video conference follow-up discussions for in-office continuing
      education. METHODS: Four small groups of practitioners (total, n = 23) were asked
      to prepare for, view, and then discuss previously recorded interactive seminars
      on a variety of subjects; a fifth group (5 previous participants) had live
      discussions of 3 topics without viewing a prerecorded seminar. All discussions
      were via video conference through typical broadband Internet connections, by
      using either WebEx (Cisco, Santa Clara, Calif) or Elluminate (Pleasanton, Calif)
      software. The participants evaluated their experiences by rating presented
      statements on a 7-point Likert scale and by providing open-ended responses.
      RESULTS: Twenty-two of the 23 participants agreed (with varying degrees of
      enthusiasm) that this was an enjoyable, effective way to learn, and that they
      would like to participate in this type of learning in the future. Everyone agreed
      that they would recommend this method of learning to others. The age and
      experience of the participants had only minor effects on their perceptions of
      acceptance and acceptability. CONCLUSIONS: The use of recorded seminars followed
      by live interaction through videoconferencing can be an acceptable and effective
      method of providing continuing education to the home or office of orthodontists
      in private practice, potentially saving them both time and travel expenses.

PMID- 21724098
TI  - Litigation and legislation. Safeguarding protected health information.

PMID- 21724099
TI  - Should we modify our indications after the EVAR-2 trial conclusions?
AB  - BACKGROUND: To compare the results of the endovascular aneurysm repair (EVAR) in
      patients considered as unfit for surgery in a "high volume" center with the EVAR
      2 trial results. METHODS: In our center, between January 2006 and December 2008,
      469 endovascular aorta treatments were performed in high-risk patients. All the
      data were prospectively collected in a database. Among 469 patients, we selected
      191 patients considered as unfit for open surgery (group 1) corresponding to the
      EVAR trial criteria. Variables such as postoperative mortality at 30 days and 1
      year, complications rates, as well as early and late redo surgery were evaluated.
      Long-term pharmacological treatment before surgery was listed. These results were
      compared with the EVAR trial (group 2). Survival during the follow-up was
      calculated according to the Kaplan-Meier method. RESULTS: Mortality at 30 days
      was 1.6% and 9% in groups 1 and 2, respectively (p = 0.002). Global complication
      rate was 44% and 43% in groups 1 and 2, respectively (p = 0.52). Over the follow
      up period, the redo surgery rate was 13% and 26% in groups 1 and 2, respectively
      (p = 0.0102). In our cohort, the survival rate at 2 years was 84% with a residual
      number of 102 patients. Before surgery, a long-term antiplatelet treatment was
      prescribed in 89% and 58% of the patients and statins in 74% and 39% of the
      patients in groups 1 and 2, respectively (p < 0.0001). CONCLUSION: The EVAR-2
      trial conclusions are in opposition to the practice of French vascular surgeons.
      Endovascular treatment of abdominal aortic aneurysms in high-risk patients is
      justified. This study confirms the importance of a multidisciplinary treatment
      for high-risk patients in high-volume centers.

PMID- 21724100
TI  - Prognostic factors of ischemic colitis after infrarenal aortic surgery.
AB  - BACKGROUND: Postoperative ischemic colitis (POIC) remains a frequent and
      extremely severe complication of infrarenal abdominal aorta surgery. However, its
      diagnosis and treatment are not always consensual because the incidence is very
      small. The aim of this retrospective study was to evaluate the prognostic factors
      of severe colitis after infrarenal aorta surgery. MATERIALS AND METHODS: We
      analyzed peroperative and perioperative data of the patients who, between 1998
      and 2004, underwent infrarenal abdominal aorta surgery and were presented with
      confirmed POIC. We set two distinct groups: acute colitis group (operated POIC,
      perioperative deaths, or evolution toward a colic stenosis secondarily operated
      on) and a moderate colitis group (recovery without aftereffects and no surgery).
      The main goal was to individualize the prognostic factors of acute colitis. Using
      the Student's t-test or the Fisher's exact test, the potential prognostic factors
      were compared between these two groups. RESULTS: Between 1998 and 2004, 679
      patients underwent infrarenal abdominal aorta surgery. Among these patients, 28
      POIC cases were confirmed: 20 patients had acute POIC and eight had moderate
      POIC. Demographic and peroperative data were similar in the two groups. Among the
      20 patients with acute POIC, 17 were operated on with a postoperative mortality
      rate of 58.8%. All the patients had at least a left colitis. In 59% of the cases,
      Hartmann's procedure was performed with a mortality rate of 50%. Early digestive
      symptoms (p = 0.05), use of vasopressors (p = 0.0377), diagnosis in intensive
      care unit (p = 0.0095), and a pH <7.35 at D1 (p = 0.0261) were independently
      associated with acute ischemic colitis. Moreover, we could observe the important
      role of endoscopy aiming at making diagnosis and prognosis. CONCLUSION: This
      study highlighted significant prognosis factors of severe colitis. These factors
      could help take the decision to operate POIC, especially to lower the effect of
      multiple organ failure syndrome (MOFS).

PMID- 21724101
TI  - Computed tomographic angiography as the primary diagnostic modality in
      penetrating lower extremity vascular injuries: a level I trauma experience.
AB  - BACKGROUND: Computed tomographic angiography (CTA) has been established as a
      valid modality for the assessment of extremity vascular injury. Over the last
      several years at our institution, CTA has evolved as the primary diagnostic
      modality for penetrating extremity injuries, largely replacing diagnostic
      angiography. The purpose of this study was to evaluate the outcomes with this
      imaging modality at a high-volume Level I trauma center. METHODS: A retrospective
      review was conducted of all patients presenting with penetrating lower extremity
      trauma between 2008 and 2009. Patient factors collected included demographics,
      mechanism of injury, injury severity, presence of hard signs of vascular injury,
      radiologic studies, operative intervention, and outcomes. RESULTS: There were 132
      patients with penetrating lower extremity trauma. The average age of the patients
      was 25 years, with an average injury severity score of 10. The injuries were
      primarily gunshot wounds (89%). In all, 59 patients (45%) underwent CTA. CTA of
      the extremity was performed as a continuation of a computed tomography of the
      chest/abdomen/pelvis in 28 (47%) versus a targeted CTA of the extremity in 31
      (53%) patients. In all, 34 (58%) CTAs were negative for vascular injury, 19 (32%)
      were positive, and six (10%) were indeterminate. Of the 34 patients with a normal
      CTA, none went to the operating room for repair of a major vascular injury;
      similarly, of the 19 patients with an abnormal CTA, there were no negative
      operative explorations. A total of 28 (21%) patients required operative
      intervention for the injured extremity; procedures performed included fasciotomy,
      venous and arterial ligation, primary repair, and interposition grafting. There
      were no amputations and no mortalities. CONCLUSIONS: Our results support the use
      of CTA as the primary imaging modality in evaluating penetrating lower extremity
      injury. Because of its proven accuracy in detecting major vascular injury, cost
      effectiveness, and ease and rapidity of administration and interpretation, CTA
      should supplant conventional angiography in initial evaluation of the patient
      presenting with penetrating trauma.

PMID- 21724102
TI  - Early postoperative hemorrhage after first rib resection for vascular thoracic
      outlet syndrome.
AB  - BACKGROUND: Thrombosis and embolization are the most frequent complications
      associated with the vascular presentation of thoracic outlet syndrome (VTOS).
      Therefore, surgery for these conditions requires careful balancing of
      anticoagulation and hemostasis. Our goal is to identify the optimal postoperative
      anticoagulation management of these patients. METHODS: A prospective database of
      consecutive patients who have presented to our institution with the diagnosis of
      thoracic outlet syndrome was reviewed from 1996 through 2010 for instances of
      postoperative hemorrhage. All venous cases were managed with transaxillary first
      rib resection followed by postoperative venography and percutaneous angioplasty
      when required. All arterial cases first underwent thrombolysis, then
      decompression with transaxillary first and cervical rib resection with
      concomitant arterial repair when indicated. RESULTS: Over the study period, 423
      patients diagnosed with thoracic outlet syndrome underwent 551 procedures. Of
      these, 108 presented with VTOS (12 arterial and 96 venous). Mean age of the
      patients in the cohort was 33.7 +/- 11.5 years, with 53 women and 55 men.
      Postoperative hemorrhage occurred in four patients (4%): three venous cases and
      one arterial case. Three patients required tube thoracostomy (average blood
      return: 800 mL) and two required video-assisted thoracoscopic surgery for
      decortication. Age, gender, preoperative anticoagulation, interval from
      thrombolysis to surgery, operative duration, and operative blood loss had no
      effect on the risk of bleeding. No hemorrhage occurred in patients treated with
      postoperative coumadin alone (82 patients) or with no anticoagulant (24
      patients). The four cases of hemorrhage occurred only in patients treated with
      postoperative low-molecular-weight heparin (LMWH; 14 patients; p < 0.01).
      CONCLUSION: Postoperative hemorrhage was not a common complication of first rib
      resection for VTOS. In our experience, it occurred exclusively in patients
      receiving LMWH postoperatively. Postoperative LMWH should be used with caution in
      patients with VTOS.

PMID- 21724103
TI  - Survival of the first arteriovenous fistula in 96 patients on chronic
      hemodialysis.
AB  - BACKGROUND: Native arteriovenous fistula (AVF) represents the best vascular
      approach for chronic hemodialysis. The aim of this study was to determine the
      survival of the first AVF and to identify the factors responsible for poor AVF
      survival. MATERIALS AND METHODS: A retrospective study was conducted on 96
      chronic hemodialysis patients benefiting from the creation and cannulation of
      their first AVF at our center, with a minimum follow-up period of 1 year. We
      collected demographic, clinical, and biological data, as well as analyzed the
      following AVF characteristics: anatomic site, cannulation time, survival, and
      complications. To identify the predictive factors of poor AVF survival, we
      defined and compared two groups of patients on the basis of whether they lost
      their first AVF during the evolution. RESULTS: Patients' mean age was 42.1 +/- 13
      years, with predominantly female patients. Mean AVF cannulation time was 17.5 +/-
      24 days. AVF loss was mainly related to thrombosis in 29% of the cases and
      stenosis in 9.4%. AVF survival was 87%, 77%, 71%, 67%, and 64% after 1, 3, 5, 8,
      and 10 years of hemodialysis, respectively. In our study, the main factors
      associated with AVF loss were lengthy jugular venous catheters placement (p =
      0.004), short AVF cannulation time after its creation (p = 0.03), and hypotension
      episodes during dialysis (p = 0.03). CONCLUSION: Long-term survival and quality
      of life in hemodialysis depend on an appropriate dialysis carried out-thanks to a
      correct vascular approach! According to the previously published data, survival
      of the first AVF can vary between 10% and 36% at 10 years. In our study, survival
      of the first native AVF was satisfying because it reached 64% at 10 years. Early
      AVF creation and prevention and management of its complications remain the safest
      and most comfortable solution to ensure AVF survival and thus a satisfying
      survival and quality of life in chronic hemodialysis patients.

PMID- 21724104
TI  - Expanding the role of endovenous laser therapy: results in large diameter
      saphenous, small saphenous, and anterior accessory veins.
AB  - BACKGROUND: Endovenous laser therapy (EVLT) is an accepted form of axial vein
      ablation for symptomatic venous reflux but there is debate regarding its efficacy
      and complication rates in large veins (>=1 cm). In addition, its role in the
      treatment of small saphenous veins (SSVs) and anterior accessory veins (AAVs) has
      not been well characterized either. METHODS: A retrospective review of patients
      undergoing EVLT on the great saphenous vein (GSV), SSV, or AAV between August
      2007 and May 2009 was conducted. A total of 885 limbs were reviewed. In all, 153
      patients were excluded because of incomplete information. Gender, age, vein size,
      operative details, ultrasound, and clinical follow-up results were recorded.
      Veins that measured <1 cm in diameter were considered small, whereas those that
      measured >=1 cm at any point were considered to be large. RESULTS: A total of 732
      ablations were reviewed, involving 175 men and 557 women (76.1%). Average follow
      up with duplex ultrasound was 3 weeks, and all patients underwent at least one
      postprocedural ultrasound. In all, 565 (77.3%) GSVs, 113 (15.5%) SSVs, and 53
      (7.3%) AAVs were treated. A total of 88 ablations were performed on veins
      measuring >= 1 cm, 12% of all treated veins. In all, 82 GSVs, three SSVs, and
      three AAVs measured >1 cm, and GSVs comprised 93.2% of treated large veins (p <=
      0.001 vs. entire cohort). For active ulceration, 4.9% of small vein and 9.1% of
      large vein treatments were performed (p = 0.11). An average of 2,983 J (range:
      250-7,922) was used for each ablation, with veins measuring >= 1 cm being treated
      with significantly more energy (3,733 vs. 2,876 J, p < 0.001). Complications
      occurred in 7.61% of small vein ablations and 7.95% of large vein ablations (p =
      0.91). This included failure in 3.4% of small vein and 4.5% of large vein
      ablations (p = 0.59). In addition, two deep vein thromboses (0.4%) occurred, both
      in GSVs. The most common complication was failure of closure, occurring in 1.6%
      of GSVs, 8.8% SSVs, and 13.2% AAVs (p < 0.001). Overall, the GSV was more likely
      to have successful closure (p <= 0.001) and fewer complications (p = 0.005) than
      SSV or AAV. CONCLUSIONS: Complication rates and closure rates are not
      significantly different for veins of diameter >= 1 cm and smaller veins. Although
      more energy is used, this has not translated into higher complication rates, thus
      making EVLT safe and effective for large vein closure. Significantly higher
      failure and complication rates were seen in SSV and AAV treatment as compared
      with GSV treatment.

PMID- 21724105
TI  - Influence of topography of an endovascular stent material on smooth muscle cell
      response.
AB  - The phenotypic shift of smooth muscle cells (SMCs) from contractile to synthetic
      phenotype after endovascular stenting has been deemed to be the predominant cause
      of restenosis. Although substrate topography has been shown to affect SMC
      response for a variety of polymers, effect of topography on phenotype of SMCs has
      not been well studied for endovascular stent materials. Thus, the objective of
      the present study was to evaluate SMC phenotype, manifested in morphology,
      proliferation, and contractile marker smooth muscle alpha-actin expression, as a
      function of 316L stainless steel topography. Results of this study showed that
      the cells grown on micro-grooved surface (groove depth: 13 MUm) were
      significantly more elongated than those on the electropolished surface.
      Ascertained by repeated proliferation studies, cells grown on micro-grooved
      surface demonstrated a significantly lower proliferation rate relative to the
      electropolished surface. An enhanced expression of smooth muscle alpha-actin
      grown on micro-grooved surface was also found near confluence. Furthermore, cells
      on electropolished surface demonstrated a substantial loss of smooth muscle alpha
      actin between days 1 and 4. Therefore, given the favorable SMC response reported
      in this study, our findings suggest that a micro-grooved topography might prove
      beneficial for endovascular stent applications.

PMID- 21724106
TI  - Rosuvastatin, a new generation 3-hydroxy-3-methylglutaryl coenzyme a reductase
      inhibitor, reduces ischemia/reperfusion-induced spinal cord tissue injury in
      rats.
AB  - BACKGROUND: Severe neurological injury still represents one of the most
      devastating complications occurring after surgical repair of thoracoabdominal
      aneurysms. We aimed to investigate the role of rosuvastatin (RSV) against
      ischemia/reperfusion injury in an experimental model of spinal cord ischemia in
      rats. METHODS: Experimental groups included control group (n = 8),
      ischemia/reperfusion group (n = 8) undergoing aortic occlusion without
      pharmacologic treatment, and RSV-treated group (n = 8) receiving 10 mg/kg/day of
      RSV orally for 3 days before spinal cord ischemia. Spinal cord ischemia was
      induced by occlusion of the abdominal aorta between the left renal artery and
      aortic bifurcation for 45 minutes, followed by reperfusion. Neurological status
      was assessed before spinal ischemia and at 48 hours postoperatively. Spinal cords
      were harvested for histopathologic examination with hematoxylin-eosin staining
      and biochemical analysis for tissue malondialdehyde, superoxide dismutase, and
      glutathione peroxidase levels. RESULTS: Decreased spinal cord tissue
      malondialdehyde levels (p = .01) and increased tissue superoxide dismutase (p =
      .01) and glutathione peroxidase (p = .09) levels were observed in the RSV-treated
      group, as compared with the ischemia group. Histopathologic analyses demonstrated
      typical changes of ischemic necrosis in the ischemia group; however, RSV
      attenuated tissue necrosis. Total injury score in the RSV-treated group was
      significantly decreased, as compared with the ischemia group (p < .05). The
      Tarlov scores at 48 hours postoperatively were higher in the RSV group as
      compared with the ischemia group. CONCLUSION: RSV administration before spinal
      cord ischemia reduces spinal cord tissue injury by increasing antioxidant enzyme
      levels and may reduce the incidence of associated neurological dysfunction.

PMID- 21724107
TI  - Endovascular repair of ascending aortic pseudoaneurysm.
AB  - We describe a complex case of ascending aortic pseudoaneurysm after open repair
      of ascending aortic aneurysm and aortic valve replacement. Although treatment was
      complicated due to intra-operative graft migration, the patient was successfully
      treated with endovascular technique.

PMID- 21724108
TI  - Endovascular treatment of symptomatic pulmonary sequestration.
AB  - Pulmonary sequestration is a rare congenital malformation whose origin is
      bronchial and arterial simultaneously and its vascularization comes from an
      anomalous systemic artery. Its clinical presentation includes recurrent
      pneumopathy in the same anatomic location of the lung and difficult to resolve or
      recurrent lung abscess. It is usually treated with antibiotherapy and eventual
      surgical resection. A 23-year-old woman with history of recurrent respiratory
      infections and three episodes of hemoptysis was admitted at the hospital.
      Computed tomography and magnetic resonance imaging confirmed diagnosis of
      pulmonary sequestration. The angiographic study showed the presence of three
      inflow arteries arising from the thoracic aorta (T10) and supplying the abnormal
      lung parenchyma at the base of the left hemithorax. The patient underwent
      endovascular treatment consisting of exclusion of the inflow vessels with
      Amplatzer occlusive devices and coils. Subsequent computed tomography angiogram
      confirmed complete infarction of the sequestration. At 7 months, the patient
      presented with a new episode of bronchial infection. Repeated angiography showed
      persistence of intermediate small nutrient branches that were treated with coil
      embolization. The patient is symptom-free at 41 months after this secondary
      procedure. Endovascular treatment of pulmonary sequestration, with selective
      embolization of the inflow arteries, is a very attractive minimally invasive
      therapeutic option, as compared with conventional surgery, and potentially less
      prone to associated complications.

PMID- 21724109
TI  - Superficial and deep vein thrombosis associated with congenital absence of the
      infrahepatic inferior vena cava in a young male patient.
AB  - BACKGROUND: Congenital absence of the inferior vena cava (AIVC) is a rare
      vascular anomaly that may be associated with deep vein thrombosis (DVT). It is
      underreported and may be present in up to 5% of young patients with DVT. We
      report a unique case of simultaneous thrombosis of both superficial and deep
      veins in a patient with AIVC. METHODS AND RESULTS: A 20-year-old man presented
      with a 2-week history of a swollen, painful, left lower limb. On examination, the
      left leg and thigh were found to be swollen and varicosities were present along
      the lower abdominal wall. Ultrasound showed extensive superficial and deep venous
      thrombosis of the entire left lower limb. Computed tomography venogram revealed
      an infrahepatic AIVC with lower limb drainage through enlarged intrathoracic
      continuations of the azygous and hemiazygous veins. The patient was put on oral
      anticoagulant therapy and was well at 6-month follow-up. CONCLUSION: The
      hypothesis for DVT in patients with AIVC is that venous drainage of the lower
      limbs is inadequate, leading to venous stasis and thrombosis. All young patients
      presenting with idiopathic DVT should be investigated for inferior vena cava
      anomalies with computed tomography if ultrasound does not visualize the inferior
      vena cava.

PMID- 21724110
TI  - An unusual combination of a tuberculous aneurysm of the thoracic aorta and a
      degenerative aneurysm of the infrarenal abdominal aorta.
AB  - Tuberculous aneurysms of the aorta are rare and give rise to various issues
      related to their diagnosis and treatment. In this article, we report on an
      exceptional case concerning a patient who presented with a false tuberculous
      aneurysm of the thoracic aorta and a degenerative aneurysm of the infrarenal
      abdominal aorta concomitantly. A discussion on how we approached the diagnosis
      and devised a therapeutic strategy that allowed us to treat this dual aortic
      disease effectively has also been provided. The discussion includes details of
      the order of treatment and the choice between an endovascular and a surgical
      approach.

PMID- 21724111
TI  - Radical correction for Budd-Chiari syndrome through a transabdominal approach.
AB  - BACKGROUND: To describe radical correction for Budd-Chiari syndrome through a
      unique transabdominal approach. METHOD: After the liver was turned leftward
      through a transabdominal approach, segments II and III of the inferior vena cava
      (IVC), the second porta hepatis, and third porta hepatis were visualized. Then,
      radical correction and angioplasty of the IVC were performed. Three patients
      operated through this approach recovered well. RESULT: All procedures were
      performed successfully, without any perioperative mortality. There were two cases
      of postoperative ascites. The elevated venous pressure and the liver function
      returned to normal at follow-up. CONCLUSION: Radical correction for Budd-Chiari
      syndrome through a transabdominal approach without extracorporeal circulation
      minimizes the surgical injury and has a good curative effect.

PMID- 21724112
TI  - Endovascular repair of complex aortic aneurysms.
AB  - Since the first published report of a fenestrated endovascular aneurysm repair,
      we have seen an expansion in the range of custom-made devices used to manage
      complex aortic aneurysms. Fenestrated devices, branched devices, and chimneys are
      now frequently used in many centers to repair these aneurysms. Similar to
      standard endovascular aneurysm repair, the advantages of less operative blood
      loss, decreased hospital stay, and reduced risk of morbidity and mortality hold
      true for endovascular repair of complex aneurysms as well. This is contrasted by
      the requirement for long-term surveillance and increased incidence of secondary
      interventions.

PMID- 21724113
TI  - Cardiac risk index and vascular surgery: not the same for everyone.

PMID- 21724115
TI  - Assessment of the cerebellar arteries with multidetector computed tomography
      angiography benefits from submillimeter slice thickness.
AB  - PURPOSE: To evaluate the accuracy of 64-row-multidetector computed tomography
      (MDCT) with different slice thickness (0.625 vs. 1.25 mm) in assessing the
      cerebellar arteries. MATERIALS AND METHODS: A total of 21 consecutive patients
      who underwent computed tomography angiography (CTA) of the cervicocranial
      arteries (64-row MDCT; slice thickness, 0.625 mm) because of suspicion of
      cerebral ischemia were enrolled retrospectively. The MDCT data set was
      secondarily reconstructed to a slice thickness of 1.25 mm. The examinations were
      reviewed by three independent blinded observers. Recorded parameters for
      reconstructed slice thicknesses of 0.625 compared to 1.25 mm were visualization
      and edge enhancement (based on a developed phantom reference model) of the
      cerebellar arteries including anterior and posterior inferior cerebellar arteries
      and the superior cerebellar artery. RESULTS: With 0.625-mm slices, significantly
      more vessel segments were visualized and edge enhancement was superior compared
      to 1.25-mm slices by the three readers, and a significant difference for the
      interaction between vessel segments and the slice thickness was found (P<.001).
      Furthermore, for a slice thickness of 1.25 mm, there was a significant difference
      in visualization (P=.0042) and edge enhancement (P=.0015) of vessel segments
      between the three readers, whereas for thinner slices (0.625 mm), no significant
      differences were found (P=.412, P=.465). CONCLUSIONS: MDCT with slice thickness
      of 0.625 mm is superior to 1.25 mm reconstructed slice thickness regarding the
      visualization of cerebellar arteries, representative for smallest assessable
      arteries in CTA. This is paralleled by a sharper edge enhancement of the vessel
      contours resulting from a reduced partial volume effect. Conclusively, cranial
      CTA protocols should be routinely optimized to generate submillimeter slices for
      diagnostic purposes and digital storage as additional diagnostic value can be
      expected.

PMID- 21724116
TI  - Multimodal imaging of recovery of functional networks associated with reversal of
      paradoxical herniation after cranioplasty.
AB  - Cranioplasty following decompressive craniectomy is reported to result in
      improved blood flow, cerebral metabolism, and concomitant neurological recovery.
      We used multimodal functional imaging technology to study a patient with marked
      neurological recovery after cranioplasty. Resting-state networks and auditory
      responses obtained with functional MRI and cerebral metabolism obtained with PET
      before and after cranioplasty revealed significant functional changes that were
      correlated with the subject's neurological recovery. Our results suggest a link
      between recovery of behavior, cerebral metabolism, and resting-state networks
      following cranioplasty.

PMID- 21724117
TI  - The role of dynamic, contrast-enhanced MRI in differentiating lung tumor
      subtypes.
AB  - The aim was to correlate dynamic magnetic resonance imaging perfusion parameters
      of pulmonary tumors with histological tumor classification. Eighty-six patients
      with lung cancer were examined. A differentiation of non-small cell lung cancer
      vs. small cell lung cancer was possible with the parameters tumor necrosis,
      maximum contrast upslope, and the time until the maximum contrast upslope was
      reached. The beginning of a relevant contrast uptake, the mean time to peak and
      the time until the maximum contrast upslope was reached allowed a differentiation
      between squamous cell carcinoma and adenocarcinoma.

PMID- 21724118
TI  - Role of carcinoembryonic antigen, magnetic resonance imaging, and positron
      emission tomography-computed tomography in the evaluation of patients with
      suspected local recurrence of colorectal cancer.
AB  - The role of carcinoembryonic antigen (CEA), magnetic resonance imaging (MRI), and
      positron emission tomography (PET)-computed tomography (CT) in detection of local
      recurrence of colorectal cancer is evaluated in 71 patients, selected due to
      suspected relapse at CT follow-up. Recurrence was confirmed by histology in 18
      cases and excluded in 25 cases. Sensitivity, specificity, positive and negative
      predictive values, and accuracy were as follows: 44.4%, 92.5%, 66.7%, 83.1%, and
      80.3% for CEA; 88.9%, 73.6%, 53.3%, 95.1%, and 77.5% for MRI; and 94.4%, 73.6%,
      54.8%, 97.5%, and 78.9% for PET-CT. A diagnostic protocol integrating CEA and
      dedicated imaging studies is to be advocated.

PMID- 21724119
TI  - Impact of different window settings on colon polyp measurements with CT virtual
      colonoscopy: a phantom study.
AB  - The aim of this study was to evaluate the impact of window settings on
      measurement of colon polyps with CT virtual colonoscopy with experiment. Twenty
      four artificial polyps' diameter were measured and scanned 10 times with
      identical scan parameters using a 64-multidetector computed tomographic scanner.
      The diameter of each polyp was measured using lung window and abdominal soft
      tissue window settings and compared with the actual diameter. The lung window
      setting offers accurate measurement of colon polyps.

PMID- 21724120
TI  - Pseudotumor of the distal common bile duct at endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND: Prior studies have described a pseudocalculus appearance in the
      distal common bile duct as a normal variant at cholangiography. The objective of
      this study was to describe the occurrence of pseudotumor in the distal common
      bile duct at endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Nine
      patients who underwent ERCP between May 2004 and July 2008 were identified as
      having a transient eccentric mural-based filling defect in the distal common bile
      duct. A single reader systematically reviewed all studies and recorded the
      imaging findings. RESULTS: The mean diameter of the filling defect was 9 mm
      (range, 5 to 11). Eight patients had resolution of the filling defect during the
      same ERCP or on a subsequent ERCP, and in two of these patients the inferior
      border of the filling defect was not well visualized. The other patient underwent
      surgical resection of a presumed tumor with no evidence of malignancy on surgical
      pathology. CONCLUSION: An eccentric mural-based filling defect in the distal
      common bile duct can be artifactual in nature and may reflect transient
      contraction of the sphincter of Oddi. Recognition of this pseudotumor may help
      avoid unnecessary surgery.

PMID- 21724121
TI  - Stiffness imaging of the kidney and adjacent abdominal tissues measured
      simultaneously using magnetic resonance elastography.
AB  - To date, non-invasive methods to detect kidney malignancies and mild tumors
      remain a challenge. The purpose of this study was to establish the proper imaging
      protocol to determine kidney stiffness and its spatial distribution within the
      various kidney compartments such as the renal sinus, medulla, and cortex. Here,
      we have used magnetic resonance elastography (MRE) along with coronal oblique
      acquisition to simultaneously measure kidney stiffness in comparison with other
      tissues including the liver, spleen, and psoas.

PMID- 21724122
TI  - Magnetic resonance spectroscopic imaging of benign prostatic tissue: findings at
      3.0 T compared to 1.5 T-initial experience.
AB  - In a retrospective study of 71 voxels of benign peripheral zone tissue from 3 men
      who underwent endorectal magnetic resonance (MR) spectroscopic imaging of the
      prostate at both 1.5 and 3 T, 21 voxels that appeared more malignant at 3 T to
      either of two readers demonstrated significantly higher levels of choline and
      polyamines at 3 T compared to 1.5 T using a Wilcoxon ranked-sum test; awareness
      of this selective amplification of these metabolic signals at high field strength
      may help avoid overdiagnosis of prostate cancer.

PMID- 21724123
TI  - CT findings of mature cystic teratoma with malignant transformation: comparison
      with mature cystic teratoma.
AB  - PURPOSE: To evaluate the imaging findings of mature cystic teratoma with
      malignant transformation (malignant teratoma) compared with the corresponding
      mature cystic teratoma (benign teratoma). MATERIALS AND METHODS: This study
      enrolled 1325 patients with 12 malignant teratomas and 1313 benign teratomas. We
      compared the computed tomographic (CT) findings of eight malignant teratomas and
      15 benign teratomas; both groups were matched in terms of tumor size (>9.9 cm)
      and patient age (>45 years). The CT images were retrospectively evaluated with
      focus on soft tissue components; size, border (regular or irregular), the
      presence or absence of nodular formation, enhancement, the angle formed between
      the soft tissue components and the inner wall of the cyst (acute or obtuse), and
      transmural growth as well as metastasis including lymphadenopathy and
      disseminated disease. Using the Fischer's Exact test, each evaluating parameter
      was compared between the two groups. RESULTS: Soft tissue components were
      observed in 75% (six of eight) of malignant teratomas and in 33% (five of
      fifteen) of benign teratomas; 100% (six of six) of soft component in malignant
      teratomas had a nodular formation and none of soft component in benign teratomas
      showed nodular formation; 83% (five of six) of soft component in malignant
      teratomas had enhancement as well as an obtuse angle between the soft tissue
      components and the inner wall of the cyst. None of soft component in benign
      teratomas showed enhancement and 20% (one of five) of soft component in benign
      teratomas had an obtuse angle; 33% (two of six) of soft component in malignant
      teratomas showed transmural growth, 13% (one of eight) of malignant teratoma
      showed lymphadenopathy, and 38% (three of eight) showed disseminated disease.
      None of benign teratomas showed transmural growth, lymphadenopathy, or
      disseminated disease. A statistically significant difference between patients
      with and without malignant transformation was seen in terms of nodular formation,
      obtuse angle, and enhancement of the soft tissue components (P<.05). CONCLUSION:
      Malignant teratoma is characterized by the following imaging findings: the
      presence of a nodular forming and enhancing soft tissue component, an obtuse
      angle between the soft tissue and the inner wall of the cyst, as well as
      extracapsular tumor growth with extension into adjacent structures or metastasis.
      Therefore, we can differentiate malignant teratoma from benign teratoma using CT
      findings.

PMID- 21724124
TI  - Evaluation of CT and MRI scanning among cancer patients in Ontario.
AB  - BACKGROUND: Computed tomography (CT) and magnetic resonance imaging (MRI)
      utilization in Ontario increased drastically since the early 1990s. The effect of
      an increased number of cancer diagnoses, and an increase in indications for scans
      has not been assessed. This study was conducted to determine trends in
      utilization of CT and MRI in cancer patients in Ontario over a period of 9 years.
      METHODS: Using Ontario Health Insurance Plan billing data linked to the Ontario
      Cancer Registry, rates of CT and MRI were analyzed by region, year, scan type and
      socioeconomic status. RESULTS: CT in cancer patients increased 2.3-fold and
      accounted for approximately 24% of these scans. MRI in cancer patients increased
      by 4.2-fold and accounted for approximately 10% of these scans. Imaging rates for
      cancer patients increased more gradually than that of the general population.
      Substantial variation in the rate of both scans by region of patient residence
      existed. Even greater variation by the location of the scanner was demonstrated,
      indicating that many cancer patients traveled outside their region for imaging.
      There was little evidence of variation in scanning rates by socioeconomic status.
      CONCLUSION: A minority of CT and MRI performed in Ontario are for cancer care.
      Regional variation in imaging rates suggest that utilization guidelines be
      developed or knowledge transfer initiatives improve compliance to existing
      guidelines are needed. A significant number of cancer patients travel outside
      their region for diagnostic imaging; this should influence decisions about the
      location of new scanners.

PMID- 21724125
TI  - Intranasal meningoencephalocele presenting as a nasal polyp--a case report.
AB  - We present a case of an intranasal meningoencephalocele masquerading as an
      'intranasal polyp' in a 17-month-old child. Nasal meningoencephaloceles are
      uncommon anomalies and require a high index of suspicion for their diagnosis.
      Biopsy of such lesions without prior imaging studies can be detrimental because
      of the risk of cerebrospinal fluid leak and meningitis, and is therefore
      contraindicated. This case reiterates the fact that any child with an intranasal
      mass should undergo appropriate imaging studies prior to excisional biopsy.

PMID- 21724126
TI  - Metastatic melanoma causing complete atrioventricular block--the role of FDG
      PET/CT in diagnosis.
AB  - Cardiac involvement with melanoma is not uncommon, but only a few are reported to
      have antemortem diagnosis. Here, we report a case of a patient with melanoma
      causing complete atrioventricular block, which is a rare complication of this
      condition. The patient had multiple metastatic lesions from melanoma and had
      undergone multiple surgeries and later developed asystole which was treated with
      a pacemaker. Echocardiogram was performed but no metastatic lesion suggested or
      detected. Cardiac metastasis was not suspected until 5 months later when the
      patient underwent a FDG PET/CT for a whole-body evaluation which was interpreted
      to be suspicious for metastasis to the myocardium. This was confirmed by a repeat
      myocardial FDG PET scan. In this case report, the role of FDG PET in melanoma
      patients with cardiac involvement is discussed.

PMID- 21724127
TI  - Solitary intraperitoneal fibrous tumor: report of three cases.
AB  - The solitary intraperitoneal fibrous tumor is a rare lesion, almost exclusively
      benign. We report on three cases with different ultrasound, computed tomography
      and magnetic resonance imaging findings, related to the fibrous and/or cellular
      histological composition of the tumor. Because of the minimal, but real,
      possibility of a recurrence after the surgical intervention, a follow-up by
      radiological imaging is recommended.

PMID- 21724128
TI  - A massive renal epithelioid angiomyolipoma with multiple metastatic lymph nodes.
AB  - A 47-year-old man presented with dull pain in the left upper abdomen for 1 year.
      Computed tomograph (CT) examination revealed a very large heterogeneously
      enhancing mass in the left kidney, measuring up to 28 cm. The mass was
      accompanied by several enlarged lymph nodes in the peri-aortic region. Radical
      nephrectomy was performed and pathologic evaluation revealed sheets of
      epithelioid cells and piecemeal necrosis consistent with malignant epithelioid
      angiomyolipoma (EAML) with regional lymph node metastases. The tumor cells were
      strongly positive for human melanosome-associated protein (HMB-45) on
      immunohistochemical staining. There was neither metastasis nor recurrence 2 years
      postoperatively. EAML is a rare tumor of mesenchymal tissue with potential for
      aggressive behavior. If this neoplasm is suspected based on CT features, EAML
      should be confirmed by pathology and immunohistochemistry.

PMID- 21724129
TI  - New women veterans in the VHA: a longitudinal profile.
AB  - OBJECTIVE: The number of women veterans using Veterans Health Administration
      (VHA) services has increased rapidly, but the characteristics of women joining
      VHA are not well understood. We sought to describe sociodemographic
      characteristics, utilization, and retention of new and returning women VHA
      patients over a 7-year period. METHODS: We identified women veterans who used VHA
      outpatient services from VHA Enrollment and Utilization files for fiscal years
      2003 through 2009. "New" patients in a given year had no outpatient use within
      the prior 3 years. Patients were "retained" if they continued to use VHA in
      subsequent years. MAIN FINDINGS: Of the 287,447 women veteran VHA outpatients in
      2009, 40,000 (14%) were new to VHA in that year and over half had joined VHA
      since 2003. Nearly two thirds of these new patients were younger than 45, and 43%
      carried a service-connected disability status. Most new patients (88%) received
      primary care services in 2008, and 40% used mental health services. Repeated use
      of mental health services (at least three visits per year) nearly doubled among
      new patients (from 11% in 2003 to 20% in 2008). Among those using VHA primary
      care in 2006, 68% of new patients versus 91% of returning patients were retained
      in either of the subsequent 2 years. CONCLUSION: The influx of new women veterans
      seeking VHA services in recent years, combined with their high rate of retention
      within VHA, contribute to the marked increase in numbers of women veterans using
      VHA. Many require fairly intensive VHA services.

PMID- 21724130
TI  - Tailoring VA primary care to women veterans: association with patient-rated
      quality and satisfaction.
AB  - BACKGROUND: Primary care delivery models tailored to women's needs and
      preferences are associated with higher quality and satisfaction. Therefore, the
      U.S. Department of Veterans Affairs (VA) recommends adoption of designated
      providers for women in primary care clinics or women's health centers as the
      optimal models for women's primary care. We assessed women veterans' ratings of
      their VA health care quality, gender-related satisfaction, gender
      appropriateness, and VA provider skills in treating women, in relation to primary
      care model at VA sites nationwide. METHODS: Health care ratings were obtained
      from VA users in the 2008-2009 National Survey of Women Veterans. VA
      administrative data identified the site for each respondent's primary care.
      Facility data identified the site's primary care model for women. We conducted
      multilevel modeling to compare health care ratings for sites serving 300 or more
      women veterans who had adopted VA recommendations for women's primary care models
      (adopter sites), with non-adopter sites, and with small sites serving fewer women
      veterans, adjusting for patient characteristics. RESULTS: Adopter sites received
      higher adjusted ratings of gender-related satisfaction and perceptions of VA
      provider skills than non-adopter and small sites. Adopter sites also received
      higher adjusted ratings of gender appropriateness than small sites. Adjusted
      ratings of quality of care did not differ by type of site. CONCLUSION: VA sites
      with primary care models tailored to women were rated higher on most dimensions
      of care. Facilitating establishment of these optimal care models at other sites
      is one strategy for improving women veterans' experiences with VA care. Research
      to identify other features of care associated with quality could inform ongoing
      VA quality transformation efforts.

PMID- 21724131
TI  - Evolving comprehensive VA women's health care: patient characteristics, needs,
      and preferences.
AB  - BACKGROUND: Assessment of women veterans' health needs and preferences and their
      care environment have been identified as a priority research need by the national
      Veterans Affairs (VA) Women's Health research agenda. Our objective was to
      identify women veterans' health care preferences and perceptions associated with
      sole or dual VA health care use. METHODS: This cross-sectional study of 1,002 VA
      enrolled Midwestern veterans was performed by computer-assisted telephone
      interviews. RESULTS: Sole and dual (both VA and non-VA) users of VA care were
      more likely to have served in a combat area, have a current diagnosis of
      posttraumatic stress disorder, and poorer physical health scores than non-VA
      users. Non-VA users were more likely to be married and have private health
      insurance. Sole VA users were more likely to want a choice of a male or female
      health care provider. Both sole and dual VA users believed that the VA provides
      adequate privacy and safety during outpatient examinations compared with non
      users. Urban women veterans were more likely to endorse specific environment of
      care preferences such as gender-specific waiting areas compared with rural
      veterans. CONCLUSION: Care preferences were similar regardless of VA use;
      however, perceptions of VA care varied. Women using VA care solely had the most
      positive perceptions of VA care, followed by dual users then non-VA users. Rural
      women were similar to urban veterans, but were less likely to endorse specific
      care preferences. Considering these differences with regard to need and access
      can inform VA policy and initiatives on improving access to and use of VA care
      among women veterans in urban and rural areas.

PMID- 21724132
TI  - National variations in VA mental health care for women veterans.
AB  - OBJECTIVES: Although the Veterans Health Administration (VA) has recently adopted
      new policies encouraging gender-specific mental health (MH) care delivery to
      women veterans, little is known about the potential difficulties local facilities
      may face in achieving compliance. We assessed variations in women's mental health
      care delivery arrangements in VA facilities nationwide. METHODS: We used results
      from the VA Survey of Women Veterans Health Programs, a key informant survey of
      senior women's health clinicians representing all VA facilities serving more than
      300 women veterans, to assess the array of gender-sensitive mental health care
      arrangements (response rate, 86%; n = 195). We also examined organizational and
      area factors related to availability of women's specialty mental health
      arrangements using multivariable logistic regression. RESULTS: Nationally, over
      half (53%) of VA facilities had some form of gender-sensitive mental health care
      arrangements. Overall, 34% of sites reported having designated women's mental
      health providers in general outpatient mental health clinics (MHCs). Almost half
      (48%) had therapy groups for women in their MHCs. VAs with women's primary care
      clinics also delivered mental health services (24%), and 12% of VAs reported
      having a separate women's MHC, most of which (88%) offered sexual trauma group
      counseling. Assignment to same-gender mental health providers is not routine. VAs
      with comprehensive women's primary care clinics were more likely to integrate
      mental health care for women as well. CONCLUSION: Local implementation of gender
      sensitive mental health care in VA settings is highly variable. Although this
      variation may reflect diverse local needs and resources, women veterans may also
      sometimes face challenges in accessing needed services.

PMID- 21724133
TI  - Description, development, and philosophies of mental health service delivery for
      female veterans in the VA: a qualitative study.
AB  - PURPOSE: National Veterans Health Administration (VA) organizational data
      suggested the presence of separate and formal mental health services for female
      veterans, prompting qualitative exploration of their structure and development.
      METHODS: Semistructured telephone interviews were conducted with a purposeful
      sample of 36 VA mental health administrators and providers from 26 VA Medical
      Centers and large community-based outpatient clinics that reported having
      separate women's mental health clinics and/or designated women's mental health
      providers in their outpatient mental health clinics. MAIN FINDINGS: VA facilities
      have implemented a spectrum of women's mental health service delivery
      arrangements, including specialized mental health providers, co-located mental
      health providers in women's health clinics, women-only mental health groups, and
      women's mental health clinics. Most facilities had one or more "champions"
      developing such services, but some faced challenges in maintaining viability.
      Some respondents expressed concern about possible stigmatization associated with
      creating separate mental health services for female veterans. CONCLUSION:
      Arrangements of VA mental health services for female veterans vary across
      facilities. This study identified a lack of consensus in the field regarding the
      need for and consequences of adapting existing programs specifically for the
      mental health needs of female veterans. Implementation of VA policy may require
      greater attention to frontline providers' perspectives. Comparative impact
      studies of female veterans' mental health service delivery arrangements are also
      needed.

PMID- 21724134
TI  - Military sexual trauma and patient perceptions of Veteran Health Administration
      health care quality.
AB  - BACKGROUND: Although sexual trauma is associated with poorer patient perceptions
      of health care quality, few studies have investigated this relationship in
      settings with comprehensive policies surrounding detection and treatment of
      sexual trauma, such as the Veterans Health Administration (VHA). We examined the
      association of military sexual trauma (MST) with patient satisfaction with VHA
      outpatient care among men and women. METHODS: This is a cross-sectional study of
      a national representative sample of 164,632 VHA outpatients (5,758 women and
      158,884 men) from fiscal year 2007. Measures included MST status, patients'
      ratings of overall satisfaction with VHA care in the last 2 months, and nine
      other dimensions of patient satisfaction. We assessed bivariate and multivariate
      associations between MST and overall satisfaction and each dimension of patient
      satisfaction. Multivariate models were adjusted for demographic characteristics,
      health status, and medical utilization. All analyses were stratified by gender.
      FINDINGS: The proportion of patients reporting very good or excellent overall
      satisfaction was 78.5% for men and 72.3% for women. Findings showed that, once
      confounding was controlled, men and women veterans' MST status was not associated
      with satisfaction ratings of VHA health care overall. However, women veterans
      with a history of MST rated the dimensions of overall coordination and education
      and information less favorably than women veterans without an MST history. Post
      hoc analysis of individual items in these domains suggested that areas of
      improvement might include greater attention to provider-patient communication,
      including communication across multiple providers. There was no association
      between men's MST status and subdomains of health care satisfaction. CONCLUSION:
      Patient ratings of overall satisfaction of VHA care are high. Opportunities
      exist, however, to educate providers on the special coordination needs of female
      veterans with histories of MST. These female veterans might benefit from care
      coordination. When investigating satisfaction in patients with histories of
      sexual trauma, our findings suggest the importance of adjusting analyses for
      important patient characteristics.

PMID- 21724135
TI  - War-related stressors as predictors of post-deployment health of Air Force women.
AB  - INTRODUCTION: Little is known about the effects of combat exposure on women's
      health after service in Operation Iraqi Freedom (OIF). Our purpose was to
      describe the incidence and nature of physical heath symptoms reported by deployed
      women to identify problematic areas where early intervention or better
      surveillance might be directed. METHODS: Using a random, stratified sample
      (theater vs. non-theater; parent vs. non-parent; and military component including
      active, guard, and reserve members) of 1,114 Air Force women, we provide
      descriptive statistics, group comparisons, and multiple regression models to
      identify health concerns and potential predictors of physical health outcomes.
      RESULTS: Findings revealed that those in the reserve/guard forces (vs. active
      duty) and those in the theater of operations (vs. elsewhere during the same time
      period) reported greater physical health problems (beta = -0.07, p < .05 and beta
      = 0.11, p < .001, respectively). Enlisted women reported poorer general health
      than officers (beta = 0.09, p < .01). Women were more likely to report that their
      physical health was impacted by OIF if deployed to the theater versus deployment
      elsewhere (beta = 0.16, p < .001) or if they were in the reserve forces (beta = 
      0.11, p < .001). Further, women who were parents or deployed to the theater
      reported greater interference of physical and emotional problems on their social
      functioning (beta = 0.08, p < .05 and beta = 0.08, p < .01, respectively).
      CONCLUSION: Deployment to the theater of operations is significantly associated
      with physical health outcomes although the severity of the self-reported symptoms
      is low. Our findings suggest that further investigation is needed to explore the
      war-related predictors of health among women serving in deployed locations around
      the world.

PMID- 21724136
TI  - Measurement of military combat exposure among women: analysis and implications.
AB  - PURPOSE: To examine combat exposure measurement instruments utilized since the
      Vietnam War, determine how these instruments were developed and psychometrically
      tested, and if they are appropriate for use with women veterans exposed to
      combat. METHODS: A literature search for articles concerning combat exposure
      instruments, their development, and their psychometric properties in relation to
      women was conducted in several electronic databases. Limited MeSH subject
      headings required keyword searches with terms such as combat stress, war trauma,
      and deployment stressors. Instruments were selected for analysis based on their
      inclusion of combat and combat-related traumatic event measures. RESULTS: Eight
      instruments were retained for critical appraisal. The majority of instruments
      were developed and validated based on male veterans' combat experiences from the
      Vietnam War through the Gulf War. Located instruments explained their
      methodological development and indicated the type of exposure being measured.
      Reliability measures for the majority were acceptable, and validity was
      established to varying degrees and with different methods. Limitations of all
      instruments included retrospective self-reporting, potential recall error, and
      the inability to validate individual exposure objectively. CONCLUSION: Women
      veterans are substantially under-represented in the development and psychometric
      testing of combat exposure instruments, indicating a male gender bias in most
      combat measures. Only two instruments utilized women veterans in their validation
      samples, and six instruments used gender-neutral terminology. Instruments
      developed and validated with male veterans for specific military conflicts may
      not reflect the combat experiences of women.

PMID- 21724137
TI  - Work-related quality of life and posttraumatic stress disorder symptoms among
      female veterans.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) can have pervasive, negative
      effects on multiple aspects of quality of life. We investigated the relationship
      between PTSD symptom clusters and work-related quality of life among female
      veterans. Although prior studies have shown that PTSD symptom clusters are
      differentially related to work-related quality of life, no study has assessed
      these relationships in women specifically. METHODS: Participants were 253 female
      veterans with current PTSD. We assessed three components of work-related quality
      of life (employment status, clinician-rated occupational impairment, and self
      rated occupational satisfaction) and performed analyses with and without
      adjusting for self-reported depression symptoms. RESULTS: None of the PTSD
      symptom clusters were associated with employment status. All PTSD symptom
      clusters had significant independent associations with occupational impairment.
      All PTSD symptom clusters except avoidance were significantly associated with
      lower occupational satisfaction, but none had independent associations with
      occupational satisfaction. No single PTSD symptom cluster emerged as most
      strongly associated with occupational outcomes. Symptoms of depression had
      substantial associations across all occupational outcomes, independent of PTSD
      symptoms. CONCLUSION: Knowledge about how PTSD relates to occupational outcomes
      in women veterans is important for addressing the needs of this growing segment
      of the VA patient population, in which PTSD is a prevalent condition. Because
      PTSD had differential relationships with the three components of work-related
      quality of life, measuring only one component, or using an aggregate measure, may
      obscure important distinctions. Resolving depression symptoms also may be
      integral to achieving meaningful recovery.

PMID- 21724138
TI  - Gender disparities in lipid-lowering therapy among veterans with diabetes.
AB  - PURPOSE: We sought to compare lipid-lowering therapy among female and male
      veterans with diabetes and hyperlipidemia. METHODS: We conducted a cross
      sectional study of veterans serviced by the Veterans Health Administration in
      2006 who had both diabetes and hyperlipidemia and compared all female patients to
      age- and facility-matched males. We compared proportions of patients with any
      prescription for lipid-lowering therapy in the year and, among those with
      elevated low-density lipoprotein cholesterol (LDL >100 mg/dL) and no prior
      treatment, we compared initiation of lipid-lowering therapy. We used multiple
      logistic regression to estimate odds ratios (AOR) and 95% confidence intervals
      (CI), adjusting for race, VA eligibility, health care utilization, cardiovascular
      diseases, mental health conditions, and a comprehensive list of other
      comorbidities. We also performed the analysis stratified by age. FINDINGS: Women
      had higher LDL levels than men (110 +/- 38 vs. 101 +/- 36 mg/dL) and were less
      likely to be receiving lipid-lowering therapy (80% vs. 84%; AOR, 0.79; 95% CI,
      0.76-0.82) or to be initiated on such therapy (37% vs. 42%; AOR, 0.82; 95% CI,
      0.74-0.90). Differences were greatest in the youngest women (<45 years old) for
      both any lipid-lowering therapy (61% vs. 75%; AOR, 0.50; 95% CI, 0.45-0.56) and
      initiation of therapy (26% vs. 38%; AOR, 0.55; 95% CI, 0.42-0.73). Adjustment for
      potential confounders did not change the risk estimates. CONCLUSION: Women
      veterans with diabetes and hyperlipidemia receive less aggressive lipid-lowering
      therapy than men, especially among younger age groups. This disparity is of
      concern, because early intervention to control hyperlipidemia can reduce the
      later burden of cardiovascular disease among diabetic women.

PMID- 21724139
TI  - Gender differences in smoking and smoking cessation treatment: an examination of
      the organizational features related to care.
AB  - OBJECTIVES: Veterans experience a particularly heavy burden with smoking rates
      higher than the general population, and the smoking prevalence for women Veterans
      has increased in recent years. We examined differences in smoking prevalence and
      treatment by gender for Veterans receiving at least some of their care at a VA
      facility, and examined the degree to which organizational factors may be
      associated with reductions in gender disparities in smoking cessation treatment.
      METHODS: We merged national organizational-level data focused on primary care
      (sites = 225) and women's health (sites = 195) with patient-level survey data (n
      = 15,033 smokers). Organizational measures focused on smoking cessation-specific
      structure and processes in primary care and women's health. Primary outcomes were
      patient-reported receipt of smoking cessation treatments-advised to quit,
      medication recommendation, and other treatment recommendation. We used multi
      level, random-intercept logistic regression. RESULTS: In 2007, 29% of women and
      23% of men were smokers. Overall, 83% of smokers reported they had been advised
      to quit, 62% recommended medications, and 60% recommended other treatments. Women
      were more likely to report being advised to quit (odds ratio, 1.33; 95%
      confidence interval, 1.07-1.64) but equally likely as men to have medications or
      other treatment recommended. Organizational factors did not eliminate the gender
      differences in being advised to quit. CONCLUSION: Despite having equivalent or
      higher smoking cessation treatment rates, women Veterans were more likely to
      smoke than men. With the rapid growth of women entering VA care, the need for
      effective gender-focused and gender-sensitive smoking cessation care arrangements
      is critical for the future health of women who have served.

PMID- 21724140
TI  - Intimate partner violence victimization among women veterans and associated heart
      health risks.
AB  - PURPOSE: Cardiovascular disease (CVD) is the leading cause of death for women in
      the United States. CVD risk factors, including depression, smoking, heavy
      drinking, being overweight, and physical inactivity, are associated with stress
      and may be linked to women's experiences of intimate partner violence (IPV)
      victimization. We know little about IPV and CVD risk factors among veteran women.
      The purpose of this study was to identify the association between lifetime IPV
      victimization and CVD risk factors among women, accounting for veteran status.
      METHODS: We used data from the Centers for Disease Control and Prevention's
      Behavioral Risk Factor Surveillance System for 2006 for the eight states that
      included the IPV module. We explored the associations between veteran status and
      lifetime IPV victimization and between IPV exposure and CVD risk factors, for
      veteran and non-veteran women. FINDINGS: Veteran women were more likely than non
      veteran women to report lifetime IPV victimization (33.0% vs. 23.8%). IPV
      exposure was associated with depression, smoking, and heavy drinking. We did not
      find evidence for an association between IPV exposure and lack of exercise or
      being overweight or obese, when controlling for demographic characteristics and
      veteran status. CONCLUSION: Women veterans have particularly high rates of
      lifetime IPV victimization. In addition, IPV victimization is associated with an
      increased risk of heart health risk factors. The findings suggest that we should
      attend to IPV exposure among veteran women and further investigate the link
      between IPV and military service, and the associated health impacts.

PMID- 21724141
TI  - Mental illness: is there an association with cancer screening among women
      veterans?
AB  - PURPOSE: Mental illness may be a barrier to achieving timely and appropriate
      cancer screening. We evaluated the association of mental illness with receipt of
      and adherence to breast, cervical, and colorectal cancer screening among women
      Veterans. METHODS: The study population included all female Veterans ages 50 to
      65 who obtained care at the New Mexico VA Health Care System continuously from
      fiscal years 2004 to 2006 (n = 606). Measures were odds ratios (OR) for receipt
      of any cancer screening, and adherence to recommended cancer screening frequency,
      adjusted for age, insurance, service connection, and primary care and women's
      clinic visits. RESULTS: Overall, 53% of the women had a mental health diagnosis
      (MHD). Women with an MHD were less likely to adhere to recommended breast cancer
      screening than women without MHD: unadjusted OR (95% CI): 0.73 (0.54-0.98; p <
      .05), adjusted OR (aOR) (95% CI) 0.60 (0.44-0.82; p < .01). Women with an MHD
      were as likely as women without MHD to receive any breast, cervical, and colon
      cancer screening: Respective aORs (95% CI): 0.79 (0.50-1.25); 1.71 (0.91-3.21);
      and 0.85 (0.56-1.28). CONCLUSION: Women with a mental illness are at risk for not
      adhering to recommended routine breast cancer screening, and may require more
      intensive efforts to achieve optimal rates of recommended breast cancer
      screening.

PMID- 21724142
TI  - "Homelessness and trauma go hand-in-hand": pathways to homelessness among women
      veterans.
AB  - BACKGROUND: Veterans comprise a disproportionate fraction of the nation's
      homeless population, with women veterans up to four times more likely to be
      homeless than non-veteran women. This paper provides a grounded description of
      women veterans' pathways into homelessness. METHODS: Three focus groups were held
      in Los Angeles, California, with a total of 29 homeless women veterans. RESULTS:
      Five predominant "roots" (precipitating experiences) initiated pathways toward
      homelessness: 1) childhood adversity, 2) trauma and/or substance abuse during
      military service, 3) post-military abuse, adversity, and/or relationship
      termination, 4) post-military mental health, substance abuse, and/or medical
      problems, and 5) unemployment. Contextual factors, which promoted development of
      homelessness in the setting of primary roots, included women veterans' "survivor
      instinct," lack of social support and resources, sense of isolation, pronounced
      sense of independence, and barriers to care. These contextual factors also
      reinforced persistence of the roots of post-military adversity and mental health
      and substance abuse problems, serving to maintain cycles of chronic homelessness.
      CONCLUSION: Collectively, these multiple, interacting roots and contextual
      factors form a "web of vulnerability" that is a target for action. Multiple
      points along the pathways to homelessness represent critical junctures for VA and
      community-based organizations to engage in prevention or intervention efforts on
      behalf of women veterans. Considering the multiple, interconnected challenges
      that these women veterans described, solutions to homelessness should address
      multiple risk factors, include trauma-informed care that acknowledges women
      veterans' traumatic experiences, and incorporate holistic responses that can
      contribute to healing and recovery.

PMID- 21724143
TI  - Psychiatric diagnoses and neurobehavioral symptom severity among OEF/OIF VA
      patients with deployment-related traumatic brain injury: a gender comparison.
AB  - BACKGROUND: Traumatic brain injury (TBI) has substantial negative implications
      for the post-deployment adjustment of veterans who served in Operation Enduring
      Freedom (OEF) and Operation Iraqi Freedom (OIF); however, most research on
      veterans has focused on males. This study investigated gender differences in
      psychiatric diagnoses and neurobehavioral symptom severity among OEF/OIF veterans
      with deployment-related TBI. METHODS: This population-based study examined
      psychiatric diagnoses and self-reported neurobehavioral symptom severity from
      administrative records for 12,605 United States OEF/OIF veterans evaluated as
      having deployment-related TBI. Men (n = 11,951) and women (n = 654) who were
      evaluated to have deployment-related TBI during a standardized comprehensive TBI
      evaluation in Department of Veterans Affairs facilities were compared on the
      presence of psychiatric diagnoses and severity of neurobehavioral symptoms.
      FINDINGS: Posttraumatic stress disorder (PTSD) was the most common psychiatric
      condition for both genders, although women were less likely than men to have a
      PTSD diagnosis. In contrast, relative to men, women were 2 times more likely to
      have a depression diagnosis, 1.3 times more likely to have a non-PTSD anxiety
      disorder, and 1.5 times more likely to have PTSD with comorbid depression.
      Multivariate analyses indicated that blast exposure during deployment may account
      for some of these differences. Additionally, women reported significantly more
      severe symptoms across a range of neurobehavioral domains. CONCLUSION: Although
      PTSD was the most common condition for both men and women, it is also critical
      for providers to identify and treat other conditions, especially depression and
      neurobehavioral symptoms, among women veterans with deployment-related TBI.

PMID- 21724144
TI  - Health and health care of women veterans and women in the military: research
      informing evidence-based practice and policy. Editor's note.

PMID- 21724145
TI  - Health and health care of women veterans and women in the military: research
      informing evidence-based practice and policy.

PMID- 21724146
TI  - VA research: committed to women who have "borne the battle" and beyond.

PMID- 21724147
TI  - Leading the nation in women's health: the important role of research.

PMID- 21724148
TI  - Using research to transform care for women veterans: advancing the research
      agenda and enhancing research-clinical partnerships.
AB  - The purpose of this paper is to report on the outcomes of the 2010 VA Women's
      Health Services Research Conference, which brought together investigators
      interested in pursuing research on women veterans and women in the military with
      leaders in women's health care delivery and policy within and outside the VA, to
      significantly advance the state and future direction of VA women's health
      research and its potential impacts on practice and policy. Building on priorities
      assembled in the previous VA research agenda (2004) and the research conducted in
      the intervening six years, we used an array of approaches to foster research
      clinical partnerships that integrated the state-of-the-science with the
      informational and strategic needs of senior policy and practice leaders. With
      demonstrated leadership commitment and support, broad field-based participation,
      strong interagency collaboration and a push to accelerate the move from
      observational to interventional and implementation research, the Conference
      provided a vital venue for establishing the foundation for a new research agenda.
      In this paper, we provide the historical evolution of the emergence of women
      veterans' health services research and an overview of the research in the
      intervening years since the first VA women's health research agenda. We then
      present the resulting VA Women's Health Research Agenda priorities and supporting
      activities designed to transform care for women veterans in six broad areas of
      study, including access to care and rural health; primary care and prevention;
      mental health; post deployment health; complex chronic conditions, aging and long
      term care; and reproductive health.

PMID- 21724149
TI  - Systematic review of women veterans' health: update on successes and gaps.
AB  - OBJECTIVE: We assessed the state of women veterans' health research by conducting
      a systematic review of scientific literature published from 2004 to 2008,
      updating a prior review spanning the history of this literature to 2004. METHODS:
      We identified articles by searching scientific databases and contacting experts.
      Relevant articles were independently evaluated by two physician reviewers. We
      categorized 195 articles by study design, funding source, period of military
      service, research topic, and health condition. RESULTS: More research was
      published during this 5-year review (n = 195) than in the 25 years beforehand (n
      = 182). The 195 studies included five trials, but only one randomized trial, a
      study that examined treatment outcomes for women with posttraumatic stress
      disorder (PTSD). The large number of articles focused on Operation Enduring
      Freedom and Operation Iraqi Freedom (OEF/OIF) soldiers' health issues (n = 23)
      reflects the growing participation of women in these conflicts. High rates of
      positive PTSD symptoms (range, 10%-19%) and other mental health disorders were
      found among OEF/OIF returning military women. The recent post-deployment
      literature underscores the need for repeated PTSD/mental health screening in
      returning veterans, and points to continuity of care needs for psychiatric and
      gynecological problems which occur in the field. The psychiatric and
      access/utilization literature confirmed the positive relationship between
      military sexual trauma and PTSD and the associated negative health effects.
      CONCLUSION: Although most VA women's health research remains observational,
      methods are evolving toward an analytical focus. Even though successes are
      evident in the breadth and depth of publications, remaining gaps in the
      literature include post-deployment readjustment for veterans/families, and
      quality-of-care interventions/outcomes for physical and mental conditions.

PMID- 21724150
TI  - A five-step guide for moving from observational studies to interventional
      research for women veterans.

PMID- 21724151
TI  - Stolen history: the great Texas textbook war.

PMID- 21724152
TI  - The whole systems medicine of tomorrow: a half-century perspective.

PMID- 21724154
TI  - Trends that will affect your future ... the rise of American theocracy, and the
      implications for science and healthcare.

PMID- 21724155
TI  - Healing the heart: a randomized pilot study of a spiritual retreat for depression
      in acute coronary syndrome patients.
AB  - BACKGROUND: Depression is associated with increased risk of cardiovascular
      morbidity and mortality in coronary heart disease. Numerous conventional and
      complementary therapies may address depression. Few involving spirituality have
      been tested. OBJECTIVE: The aim of this study was to compare the effects of a
      nondenominational spiritual retreat, Medicine for the Earth (MFTE), on depression
      and other measures of well-being six- to 18-months post acute coronary syndrome
      (ACS). DESIGN/SETTING: A randomized controlled pilot study of MFTE, Lifestyle
      Change Program (LCP), or usual cardiac care (control) was conducted in
      Southeastern Michigan. PARTICIPANTS: ACS patients were recruited via local and
      national advertising (n = 58 enrolled, 41 completed). INTERVENTIONS: The four-day
      MFTE intervention included guided imagery, meditation, drumming, journal writing,
      and nature-based activities. The four-day LCP included nutrition education,
      exercise, and stress management. Both retreat groups received follow-up phone
      coaching biweekly for three months. MAIN OUTCOME MEASURES: Validated self-report
      scales of depression, spiritual well-being, perceived stress, and hope were
      collected at baseline, immediately post-retreat, and at three and six months.
      RESULTS: Depression was not significantly different among groups (P = .21).
      However, the MFTE group had the highest depression scores at baseline and had
      significantly lower scores at all postintervention time points (P <= .002). Hope
      significantly improved among MFTE participants, an effect that persisted at three
      and six-month follow-up (P = .014). Although several measures showed improvement
      in all groups by six months, the MFTE group had immediate improvement post
      retreat, which was maintained. CONCLUSIONS: This pilot study shows that a
      nondenominational spiritual retreat, MFTE, can be used to increase hope while
      reducing depression in patients with ACS.

PMID- 21724156
TI  - Impact of spirituality/religiosity on mortality: comparison with other health
      interventions.
AB  - Scientists have been interested in the influence of religion on mortality for at
      least 130 years. Since this time, many debates have been held by researchers who
      believe or do not believe in this association. The objective of this study is to
      compare the impact of spirituality and religiosity (S/R) with other health
      interventions on mortality. The authors selected 25 well-known health
      interventions. Then, a search of online medical databases was performed. Meta
      analyses between 1994 and 2009 involving mortality were chosen. The same was done
      for religiosity and spirituality. The combined hazard ratio was obtained directly
      by the systematic reviews and the mortality reductions by S/R and other health
      interventions were compared. Twenty-eight meta-analyses with mortality outcomes
      were selected (25 health interventions and three dealing with S/R). From these
      three meta-analyses, considering those with the most conservative results,
      persons with higher S/R had an 18% reduction in mortality. This result is
      stronger than 60.0% of the 25 systematic reviews analyzed (similar to consumption
      of fruits and vegetables for cardiovascular events and stronger than statin
      therapy). These results suggest that S/R plays a considerable role in mortality
      rate reductions, comparable to fruit and vegetable consumption and statin
      therapy.

PMID- 21724157
TI  - Pain modulation by meditation and electroacupuncture in experimental submaximum
      effort tourniquet technique (SETT).
AB  - CONTEXT: Although acupuncture and meditation are widely utilized in the clinical
      treatment of pain, trials to evaluate their efficacy and modes of action under
      experimental conditions have yielded equivocal results. OBJECTIVE: This
      feasibility study investigated whether electroacupuncture (EA) and meditation
      effectively relieve pain within a well-established ischemic pain paradigm
      (submaximum effort tourniquet technique, SETT). DESIGN: In this semirandomized
      trial, experienced meditators were compared with nonmeditators. The nonmeditating
      subjects were randomly assigned to either an EA group or a nontreatment group.
      SETTING: The trial was conducted at the Department of Complementary and
      Integrative Medicine, University of Duisburg-Essen, Essen, Germany. PARTICIPANTS:
      Eight Vipassana meditators (mean experience hours = 2,626.8 +/- 1,602.3 hours SD)
      and 40 control subjects were enrolled. INTERVENTIONS: SETT (250 mm Hg, time limit
      = 30 minutes, pain rating limit = 10) was applied twice (baseline vs treatment)
      on the nondominant arm; EA was applied to the contralateral acupoints LI4 and
      LI10 (stimulation 20 minutes prior to and throughout the SETT); meditators were
      asked to meditate throughout the whole experimental procedure. MAIN OUTCOME
      MEASURE: Pain ratings were obtained every three minutes on a numerical rating
      scale (0-10). The ratio of the tolerated time to the ratings served as the pain
      tolerance index. RESULTS: At baseline, meditators exhibited significantly greater
      pain tolerance than the other two groups. During the second or treatment session,
      pain sensitivity did not change significantly in the nontreatment group, whereas
      pain tolerance significantly increased and pain ratings decreased to the level of
      meditation-induced analgesia in the EA group. Electroacupuncture induced no
      additional pain control benefit for meditators.

PMID- 21724158
TI  - Evidence for a communal consciousness.
AB  - Recently described social network phenomena show that emotionally connected
      people come to share certain traits, including obesity, happiness, and
      loneliness. These do not appear to be mediated by face-to-face contact. Other
      examples of groups with a common connection that act in unison are mass hysteria,
      menstrual synchrony, and the ability of a group to guess the number of jelly
      beans in a jar. The animal kingdom abounds with examples of groups functioning as
      a single whole: fish school, birds flock, hoofed animals herd, ant and bee
      colonies work as a single organism. Try as they might, neuroscientists have been
      unable to find an anatomical seat of consciousness within the brain. C.G. Jung's
      realization of a collective unconscious began with an observation of a patient
      whose thoughts matched previous writings that the patient had never seen. The
      "emotional telepathy" of social network phenomena suggests a collective/communal
      consciousness as well.

PMID- 21724160
TI  - mHealth (mobile health)-using Apps for health and wellness.

PMID- 21724159
TI  - Building bridges: qualitative assessment of a clinical faculty exchange between a
      naturopathic and an allopathic medical training program.
AB  - RESEARCH QUESTION: What are the perceived benefits of a clinical exchange
      experience designed as part of a program to promote acceptance and use of
      evidence-based medicine (EBM) in naturopathic clinical practice? METHODS: Nine
      faculty members participated in a focus group (n = 6) or a structured interview
      (n = 3) to assess experience in the program. Investigators independently analyzed
      transcribed notes for common experience themes. ANALYSIS AND INTERPRETATION: Six
      major themes emerged: integrating EBM into naturopathic clinical teaching,
      strengthening of professional relationships, exposure to clinical experiences
      outside the usual naturopathic scope, reaffirmation of naturopathic training and
      profession, observation of clinical and administrative resources and practices,
      and recommendations for future clinical exchanges. MAIN RESULTS: A clinical
      exchange experience was viewed as a favorable way to promote EBM appreciation
      within the complementary and alternative medicine educational community and to
      foster improved clinical experiences for faculty and their students and patients.

PMID- 21724161
TI  - Past and future.

PMID- 21724162
TI  - Commentary on the Cochrane review of stimulation of the wrist acupuncture point
      p6 for preventing postoperative nausea and vomiting.

PMID- 21724163
TI  - Advancing evidence informed practice through faculty development: the
      Northwestern Health Sciences University model.

PMID- 21724164
TI  - Population genetics of ectomycorrhizal fungi: from current knowledge to emerging
      directions.
AB  - Ectomycorrhizal (EM) fungi are major microbial components of boreal, temperate
      and Mediterranean forests, as well as some tropical forest ecosystems. Nearly two
      decades of studies have clarified many aspects of their population biology, based
      on several model species from diverse lineages of fungi where the EM symbiosis
      evolved, i.e. among Hymenomycetes and, to a lesser extent, among Ascomycetes. In
      this review, we show how tools for individual recognition have changed, shifting
      from the use of somatic incompatibility reactions to dominant and non-specific
      markers (such as random amplified polymorphic DNA (RAPD) and amplified fragment
      length polymorphism (AFLP)) and, more recently, to co-dominant and specific
      markers (such as microsatellites and single nucleotide polymorphisms (SNPs)). At
      the same time, the theoretical focus has also changed. In earlier studies, a
      major aim was the description of genet size and popul/ation strategy. For
      example, we show how some studies supported or challenged the simple, classical
      model of colonization of new forest stands by ruderal (R) species, propagating by
      spores and forming small genets, progressively replaced in older forests by more
      competitive (C) species, propagating by mycelial growth and forming larger
      genets. By contrast, more recent studies give insights into some genetic traits,
      such as partners' assortment (allo- versus autogamy), genetic structure of
      populations and gene flow that turn out to depend both on distance and on whether
      spores are animal- or wind-dispersed. We discuss the rising awareness that (i)
      many morphospecies contain cryptic biological species (often sympatric) and (ii)
      trans- and inter-continental species may often contain several biological species
      isolated by distance. Finally, we show the emergence of biogeographic approaches
      and call for some aspects to be developed, such as fine-scale and long-term
      population monitoring, analyses of subterranean populations of extra-radical
      mycelia, or more model species from the tropics, as well as from the Ascomycetes
      (whose genetic idiosyncrasies are discussed). With the rise of the '-omics'
      sciences, analysis of population structure for non-neutral genes is expected to
      develop, and forest management and conservation biology will probably profit from
      published and expected work.

PMID- 21724165
TI  - Three new phylogenetic lineages are the closest relatives of the widespread
      species Albugo candida.
AB  - White blister rust caused by the obligate biotroph Albugo candida (Albuginaceae;
      Oomycota) is one of the most notorious and common diseases of Brassicaceae.
      During the past 5 y, A. candida specimens collected from about 30 host genera
      were phylogenetically and morphologically investigated in several studies. These
      not only revealed that A. candida s.str. has a broad host range, encompassing a
      large number of host plants belonging to Brassicales, but also the presence of
      previously overlooked species of Albugo with hosts in this order. In this study,
      we examined specimens from Alyssum, Barbarea, and Rorippa, of which many species
      were commonly recorded as host plants of A. candida but could not be included in
      previous works due to the paucity of specimens available. It was revealed that
      Albugo specimens from Alyssum montanum, Barbarea vulgaris, and various Rorippa
      species, were placed in three phylogenetically distinct clades, but closer to A.
      candida s.str. than any previously reported species. Oospores were observed from
      Albugo specimens parasitic to Rorippa and could be distinguished morphologically
      from A. candida. Therefore, Albugo rorippae sp. nov. is described and illustrated
      here. In addition, a key of Albugo species described previously from Brassicales
      is given. The present study reveals that a large number of Albugo species remain
      still undiscovered, and that species close to A. candida exist. This could help
      elucidating the basis of the broad host range of A. candida as opposed to the
      narrow specialisation that is seemingly present in other species of Albugo on the
      Brassicaceae.

PMID- 21724166
TI  - Ophiocordyceps halabalaensis: a new species of Ophiocordyceps pathogenic to
      Camponotus gigas in Hala Bala Wildlife Sanctuary, Southern Thailand.
AB  - Several fungal pathogens of ants have been reported as members of the family
      Ophiocordycipitaceae in the order Hypocreales. Surveys in the south of Thailand
      have shown specimens showing characteristics that are morphologically similar to
      Ophiocordyceps unilateralis, a very common ant pathogen, by producing a lateral
      pad on one side of the stroma and producing whole ascospores. Phylogenetic
      analyses of the partial elongation factor tef1-alpha and the internal transcribed
      spacer regions ITS1-5.8S-ITS2 rDNA have shown that this is a distinct species
      from O. unilateralis. The morphological characters of Ophiocordyceps
      halabalaensis differs from O. unilateralis in the possession of bigger perithecia
      and ascospores, and molecular analyses have shown that this ant-specific fungus
      is sufficiently different from O. unilateralis, deserving the naming of a new
      species. Aspects of morphology, host association/host-specificity, and taxonomic
      position are discussed.

PMID- 21724167
TI  - Molecular organization of the mating-type loci in the homothallic Ascomycete
      Eupenicillium crustaceum.
AB  - Eupenicillium species are the teleomorphic (sexual) forms of anamorphic (asexual)
      members of the genus Penicillium, which contains many species of industrial
      importance. Here we describe the first molecular analysis of the mating-type
      (MAT) locus from a homothallic (self-fertile) Eupenicillium species, E.
      crustaceum. This ascomycete is a sexual relative of the penicillin producer
      Penicillium chrysogenum, which while long considered asexual, was recently shown
      to possess the required genetic machinery for heterothallic breeding. The E.
      crustaceum genome contains two MAT loci, MAT1-1 and MAT1-2, in an arrangement
      characteristic of other known homothallic euascomycetes, such as Neosartorya
      fischeri. MAT1-1 is flanked by conserved APN2 (DNA lyase) and SLA2 (cytoskeleton
      assembly control) genes and encodes a homologue of the alpha-box domain protein
      MAT1-1-1. Conversely, MAT1-2 carries a HMG-domain gene MAT1-2-1, and is flanked
      by a degenerate SLA2 gene and an intact homologue of the P. chrysogenum ORF
      Pc20g08960. Here we demonstrate the transcriptional expression of both mating
      type genes during vegetative development. Furthermore, the MAT1-1-1 and MAT1-2-1
      sequences were used to resolve the phylogenetic relationship of E. crustaceum
      with other ascomycetes. Phylogenetic trees confirmed a very close relationship
      between the homothallic E. crustaceum and the supposedly heterothallic P.
      chrysogenum. This close taxonomic association makes E. crustaceum an ideal
      candidate for future expression and evolutionary studies of sexual reproduction,
      with the ultimate aim of inducing sex in P. chrysogenum.

PMID- 21724168
TI  - The allergenicity of Aspergillus fumigatus conidia is influenced by growth
      temperature.
AB  - Common indoor and outdoor environmental fungi such as Aspergillus fumigatus
      produce asexual spores containing a collection of proteins that can bind IgE
      antibodies and trigger allergic reactions. We characterized the impact of
      sporulation temperature on the IgE-binding capacity (allergenicity) of A.
      fumigatus and explored the links between variable allergenicity and temperature
      dependant expression of genes encoding these allergenic proteins. A 12-fold
      increase in A. fumigatus allergenicity per spore was observed when sporulation
      temperatures were decreased from 32 degrees C to 17 degrees C. Per spore protein
      mass and Asp f 1 allergen mass also followed this trend. Functional gene
      expression analysis of A. fumigatus sporulating cultures by real-time reverse
      transcription PCR and gene expression microarrays revealed that a greater number
      of genes encoding known, major allergens are more highly expressed at lower
      sporulation temperatures. The results of this study indicate that environmental
      conditions at growth significantly influence the allergenicity of this common
      mould through the differential production of allergenic proteins, and highlight
      the importance of in vivo or in vitro allergenicity measurements for
      understanding environmental exposure to airborne allergenic fungi.

PMID- 21724169
TI  - Transient transformation of the obligate biotrophic rust fungus Uromyces fabae
      using biolistics.
AB  - Obligate biotrophic pathogens like the rust fungi are important plant pathogens
      causing enormous losses on food, forage and biomass crops. The analysis of the
      molecular details underlying obligate biotrophic host-parasite interactions is
      mainly hampered by the fact that no system for transformation is available for
      most obligate biotrophic organisms. Here we report the transient transformation
      of Uromyces fabae, an obligate biotrophic rust fungus using a biolistic approach.
      Biolistic bombardment of U. fabae urediospores was used to deliver different
      color markers (beta-glucuronidase (GUS), intron green fluorescent protein (iGFP)
      and red fluorescent protein (DsRed) and/or a selection marker. Endogenous
      regulatory elements from U. fabae plasma membrane ATPase (Uf-PMA1) were used to
      drive expression of the transgenes. In addition to the delivery of color markers,
      an in planta selection procedure using the fungicide Carboxin was established
      allowing the propagation of transformants. In addition to mere cytoplasmic
      expression of the color markers, a nuclear localization signal was fused to DsRed
      (pRV115-NLS) targeting the fluorescent marker protein to the nuclei. A procedure
      for the genetic modification of U. fabae was established. The method can be
      easily adapted for use with other obligate biotrophic fungi. This provides the
      basis for a more in depth analysis of the molecular principles governing the
      obligate biotrophic lifestyle.

PMID- 21724170
TI  - Elemental composition in vesicles of an arbuscular mycorrhizal fungus, as
      revealed by PIXE analysis.
AB  - We investigated element accumulation in vesicles of the arbuscular mycorrhizal
      (AM) fungus Glomus intraradices, extracted from the roots of inoculated leek
      plants. The elemental composition (elements heavier than Mg) was quantified using
      particle-induced X-ray emission (PIXE), in combination with scanning transmission
      ion microscopy (STIM). In vesicles, P was the most abundant of the elements
      analysed, followed by Ca, S, Si and K. We analysed 12 vesicles from two root
      systems and found that the variation between vesicles was particularly high for P
      and Si. The P content related positively to Si, Zn and K, while its relation to
      Cl fitted to a negative power function. Vesicle transects showed that P and K
      were present in central parts, while Ca was present mainly near the vesicle
      surfaces. The results showed that P is an important part (0.5% of the dry weight)
      of the vesicle content and that the distribution of some elements, within
      mycelia, may be strongly correlated.

PMID- 21724171
TI  - Absence of isolation by distance patterns at the regional scale in the fungal
      plant pathogen Leptosphaeria maculans.
AB  - Outcomes of host-pathogen coevolution are influenced by migration rates of the
      interacting species. Reduced gene flow with increasing spatial distance between
      populations leads to spatial genetic structure, as predicted by the isolation by
      distance (IBD) model. In wind-dispersed plant-pathogenic fungi, a significant
      spatial genetic structure is theoretically expected if local spore dispersal is
      more frequent than long-distance dispersal, but this remains to be documented by
      empirical data. For 29 populations of the oilseed rape fungus Leptosphaeria
      maculans sampled from two French regions, genetic structure was determined using
      eight minisatellite markers. Gene diversity (H = 0.62-0.70) and haplotypic
      richness (R = 0.96-1) were high in all populations. No linkage disequilibrium was
      detected between loci, suggesting the prevalence of panmictic sexual
      reproduction. Analysis of molecular variance showed that > 97% of genetic
      diversity was observed within populations. Genetic differentiation was low among
      populations (F(st) < 0.05). Although direct methods previously revealed short
      distance dispersal for L. maculans, our findings of no correlation between
      genetic and geographic distances among populations illustrate that the IBD model
      does not account for dispersal of the fungus at the spatial scale we examined.
      These results indicate high gene flow among French populations of L. maculans,
      suggesting high dispersal rates and/or large effective population sizes, two
      characteristics giving the pathogen high evolutionary potential against the
      deployment of resistant oilseed rape cultivars.

PMID- 21724172
TI  - DsRNA-free transmissible hypovirulence associated with formation of intra-hyphal
      hyphae in Botrytis cinerea.
AB  - A spontaneous mutant CanBc-3HV and its parental strain CanBc-3 of Botrytis
      cinerea were investigated in terms of pathogenicity, colony morphology,
      hypovirulence transmissibility, presence of double-stranded RNA (dsRNA), and
      formation of intra-hyphal hyphae (IH). Results showed that inoculation of CanBc
      3HV on detached leaves of Brassica napus did not produce any visible necrotic
      lesions (20 degrees C, 72h), whereas inoculation of CanBc-3 caused necrotic leaf
      lesions. Compared to CanBc-3, CanBc-3HV grew slowly, formed numerous mycelial
      sectors, sporulated sporadically and failed to produce sclerotia on potato
      dextrose agar (PDA) (20 degrees C, 15d). Hypovirulence and the abnormal cultural
      characteristics of CanBc-3HV were transmissible from CanBc-3HV to CanBc-3 in pair
      cultures on PDA. However, the transmission was unsuccessful from CanBc-3HV to
      another virulent strain CanBc-2 of B. cinerea. These results suggest that
      transmission of the hypovirulence and the abnormal cultural characteristics of
      CanBc-3HV are strain-specific. No dsRNA was detected in mycelia of either CanBc
      3HV or CanBc-3, implying that the hypovirulence of CanBc-3HV is caused by a
      transmissible element (TE) of non-RNA mycoviral origin. Formation of IH through
      self-infection was observed in CanBc-3HV, CanBc-3T1 (a hypovirulent derivative of
      CanBc-3 trans-infected by TE in CanBc-3HV), but was not observed in CanBc-3,
      suggesting that IH formation is associated with the hypovirulence of CanBc-3HV.
      To our knowledge, this is the first report of dsRNA-free transmissible
      hypovirulence associated with IH formation in B. cinerea.

PMID- 21724173
TI  - Touchdown nested multiplex PCR detection of Phytophthora cinnamomi and P.
      cambivora from French and English chestnut grove soils.
AB  - Soil borne Phytophthora cinnamomi and Phytophthora cambivora are considered the
      most pathogenic species associated with chestnut (Castanea sativa) decline in
      Europe. Mapping their incidence and distribution from nursery and plantation
      soils may offer valuable information for limiting spread. As conventional
      biological baiting and taxonomic confirmation is generally time consuming,
      labour, logistically and space intensive, we have focused on the development of a
      specific touchdown nested multiplex Polymerase Chain Reaction (PCR) approach for
      the simultaneous detection of both species direct from soil. Pre-existing and
      novel primers, based on Internal Transcribed Spacer (ITS) sequences, have been
      evaluated for their specificity and use in a multiplex capacity in various
      combinations. Coupled to this we have modified a mechanical lysis procedure for
      DNA extraction from up to 10 g of chestnut under storey soils (ranging from 0.5
      to 25 MUg DNA g(-1)fresh soil). Using serial dilutions and/or
      polyvinylpolypyrrolidone chromatography purification, both species have been
      successfully detected, in artificially and naturally infected soils. Levels of
      assay detection are comparable to other Phytophthora species where PCR based
      diagnostic systems have been reported. A qualitative evaluation of this approach
      against conventional baiting is presented.

PMID- 21724175
TI  - Editorial: comfort and discomfort studies demonstrate the need for a new model.
AB  - The term comfort is often seen relating to the marketing of products like chairs,
      cars, clothing, hand tools and even airplane tickets, while in the scientific
      literature, the term discomfort shows up often, since it is used in research. Few
      papers explain the concept of a localized comfort experience in relation to
      product use, although people use these products daily. Therefore, in this special
      issue, the concept of product comfort is studied further. In this editorial an
      overview of comfort models has been made, evaluated with the papers from the
      special issue and a new comfort/discomfort model is proposed to increase our
      understanding of the factors influencing comfort and discomfort experiences.

PMID- 21724174
TI  - Expressed sequence tags reveal genetic diversity and putative virulence factors
      of the pathogenic oomycete Pythium insidiosum.
AB  - Oomycetes are unique eukaryotic microorganisms that share a mycelial morphology
      with fungi. Many oomycetes are pathogenic to plants, and a more limited number
      are pathogenic to animals. Pythium insidiosum is the only oomycete that is
      capable of infecting both humans and animals, and causes a life-threatening
      infectious disease, called "pythiosis". In the majority of pythiosis patients
      life-long handicaps result from the inevitable radical excision of infected
      organs, and many die from advanced infection. Better understanding P. insidiosum
      pathogenesis at molecular levels could lead to new forms of treatment. Genetic
      and genomic information is lacking for P. insidiosum, so we have undertaken an
      expressed sequence tag (EST) study, and report on the first dataset of 486 ESTs,
      assembled into 217 unigenes. Of these, 144 had significant sequence similarity
      with known genes, including 47 with ribosomal protein homology. Potential
      virulence factors included genes involved in antioxidation, thermal adaptation,
      immunomodulation, and iron and sterol binding. Effectors resembling pathogenicity
      factors of plant-pathogenic oomycetes were also discovered, such as, a CBEL-like
      protein (possible involvement in host cell adhesion and hemagglutination), a
      putative RXLR effector (possibly involved in host cell modulation) and elicitin
      like (ELL) proteins. Phylogenetic analysis mapped P. insidiosum ELLs to several
      novel clades of oomycete elicitins (ELIs), and homology modeling predicted that
      P. insidiosum ELLs should bind sterols. Most of the P. insidiosum ESTs showed
      homology to sequences in the genome or EST databases of other oomycetes, but one
      putative gene, with unknown function, was found to be unique to P. insidiosum.
      The EST dataset reported here represents the first steps in identifying genes of
      P. insidiosum and beginning transcriptome analysis. This genetic information will
      facilitate understanding of pathogenic mechanisms of this devastating pathogen.

PMID- 21724176
TI  - An evaluation of the enhanced cognitive-behavioural model of bulimia nervosa.
AB  - The original cognitive-behavioural model of bulimia nervosa (BN) has been
      enhanced to include four additional maintaining mechanisms: low self esteem,
      clinical perfectionism, interpersonal problems, and mood intolerance. These
      models have been used to guide cognitive-behavioural treatment for BN, but the
      enhanced model has yet to be directly evaluated as a whole in a clinical sample.
      This study aimed to compare and evaluate the original and the enhanced cognitive
      behavioural models of BN using structural equation modelling. The Eating Disorder
      Examination and self-report questionnaires were completed by 162 patients seeking
      treatment for BN (N = 129) or atypical BN (N = 33). Fit indices suggested that
      both the original and enhanced models provided a good fit to the data, but the
      enhanced model accounted for more variance in dietary restraint and binge eating.
      In the enhanced model, low self esteem was associated with greater overevaluation
      of weight and shape, which, in turn, was associated with increased dietary
      restraint. Interpersonal problems were also directly associated with dietary
      restraint, and binge eating was associated with increased purging. While the
      current study provides support for some aspects of the enhanced cognitive
      behavioural model of BN, some key relationships in the model were not supported,
      including the important conceptual relationship between dietary restraint and
      binge eating.

PMID- 21724177
TI  - Glutamatergic Kolliker-Fuse nucleus neurons innervate hypoglossal motoneurons
      whose axons form the medial (protruder) branch of the hypoglossal nerve in the
      rat.
AB  - This study was performed to understand the anatomical substrates for Kolliker
      Fuse nucleus (KFN) modulation of respiratory-related tongue movement. After
      application of cholera toxin B subunit (CTb) to the medial branch of the
      hypoglossal nerve (HGn) and injection of biotinylated dextran amine (BDA) into
      the KFN ipsilaterally, an overlapping distribution of BDA-labeled axon terminals
      and CTb-labeled neurons was found in the ventral compartment of the hypoglossal
      nucleus (HGN) ipsilateral to the application and injection sites. At the electron
      microscopic level, the BDA-labeled terminals made asymmetrical synaptic contacts
      predominantly with dendrites of the HGN neurons, some of which were labeled with
      CTb. Using retrograde tracing combined with in situ hybridization, we
      demonstrated that almost all the KFN neurons sending their axons to the HGN were
      positive for vesicular glutamate transporter (VGLUT) 2 mRNA but not glutamic acid
      decarboxylase 67 mRNA. Using a combination of anterograde and retrograde tracing
      techniques and immunohistochemistry for VGLUT2, we further demonstrated that the
      KFN axon terminals with VGLUT2 immunoreactivity established close contact with
      the HGN motoneurons whose axons constitute the medial branch of the HGn. The
      present results suggest that glutamatergic KFN fibers may exert excitatory
      influence upon the HGN motoneurons sending their axons to the medial branch of
      the HGn for the control of protruder tongue muscles contraction to maintain
      airway patency during respiration.

PMID- 21724178
TI  - Historical concepts on the relations between nerves and muscles.
AB  - This review addresses the history since antiquity of studies on the anatomical
      and functional relations between nerves and muscles, and the progressive use of
      newer approaches to this topic. By the Hippocratic era (almost 2500 years ago)
      the digestive, circulatory and nervous systems were thought to participate in the
      production of animal spirits. This concept had strong support for nervous
      conduction, even after the dawn of electrophysiology in the late 18th C. The idea
      that these spirits explained the nature of the motor command to muscles continued
      to prevail until work in the mid-to-late 19th C dispelled the concept of
      "fluid/spirit" transmission by measurements of nerve "action currents" and
      conduction velocity. In parallel with this work, the functional relations between
      nerves and muscles were studied with the use of curare, which continued well into
      the 20th C. In the late 19th C the debate was formalized about whether
      transmission at the motor endplate was electrical or chemical, which continued as
      the "soup" vs. "sparks" battle until, surprisingly, the late 1960s. The concept
      of the motor unit was introduced in the 1920s, this being defined as a motor
      neuron in the spinal cord connecting to a specific set of muscle fibers. This
      development accelerated work on two-way trophic relations between nerve and
      muscles and their essential plasticity in response to the demands of usage and
      disease. Thus, the relation between nerves and muscles has been on the forefront
      of neuroscience since antiquity.

PMID- 21724179
TI  - B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and
      proliferation.
AB  - It is controversial whether naive B cells are directly activated in response to
      TLR9 ligand, CpG ODN. Although bovine blood-derived CD21(+) B cells express TLR9
      and proliferate in response to CpG in mixed-cell populations, purified bovine B
      cells do not proliferate significantly in response to CpG ODN, even when the B
      cell receptor is engaged. When co-cultured with CD14(+) myeloid cells and/or B
      cell activating factor (BAFF), a cytokine produced by activated myeloid cells,
      there was a significant increase in CpG-specific B cell proliferation, and the
      number of large B cells in general or positive for CD25, all of which are markers
      for B cell activation. These data suggest that activated myeloid cells and BAFF
      prime B cells for significant CpG-specific activation. Understanding the signals
      required to mediate efficient CpG-induced, antigen-independent and T-cell
      independent activation of B cells has implications for polyclonal B cell
      activation and the development of autoimmune diseases.

PMID- 21724181
TI  - [Another application of the STRATOS system for the correction of chest wall
      deformities. Repeat surgery of pectus excavatum after failure of a Ravitch
      procedure].

PMID- 21724180
TI  - Galectins distinctively regulate central monocyte and macrophage function.
AB  - Monocytes and macrophages link the innate and adaptive immune systems and protect
      the host from the outside world. In inflammatory disorders their activation leads
      to tissue damage. Galectins have emerged as central regulators of the immune
      system. However, if they regulate monocyte/macrophage physiology is still
      unknown. Binding of Gal-1, Gal-2, Gal-3 and Gal-4 to monocytes/macrophages,
      activation, cytokine secretion and apoptosis were determined by FACS, migration
      by Transwell system and phagocytosis by phagotest. Supernatants from macrophages
      co-cultured with galectins revealed their influence on T-cell function. In our
      study Gal-1, Gal-2, Gal-4, and partly Gal-3 bound to monocytes/macrophages.
      Galectins prevented Salmonella-induced MHCII upregulation. Cytokine release was
      distinctly induced by different galectins. T-cell activation was significantly
      restricted by supernatants of macrophages co-cultured in the presence of Gal-2 or
      Gal-4. Furthermore, all galectins tested significantly inhibited monocyte
      migration. Finally, we showed for the first time that galectins induce potently
      monocyte, but not macrophage apoptosis. Our study provides evidence that
      galectins distinctively modulate central monocyte/macrophage function. By
      inhibiting T-cell function via macrophage priming, we show that galectins link
      the innate and adaptive immune systems and provide new insights into the action
      of sugar-binding proteins.

PMID- 21724182
TI  - Simple weight-based contrast dosing for standardization of portal phase CT liver
      enhancement.
AB  - AIM: To investigate the use of a weight-based volume of contrast media to
      optimize portal enhancement in patients undergoing abdominal computed tomography
      (CT). MATERIALS AND METHODS: Thirty-one patients were assessed to establish
      whether a relationship existed between their weight and the portal liver
      enhancement achieved. Three methods of estimating weight were evaluated to
      establish which was the most appropriate to use in clinical practice. One hundred
      patients were then examined using 100 ml contrast media and 100 further patients
      using a weight-based contrast volume as dictated by a look-up table. The
      enhancement achieved by each technique was assessed. RESULTS: A good correlation
      was shown between patient weight and contrast enhancement when a fixed volume of
      contrast media was used (r=-0.825, p<0.0001). Asking the patient was shown to be
      the most appropriate method for estimating their weight. The mean portal liver
      enhancement using the fixed dose and weight-adjusted dose were 110 HU (SD=25.1)
      and 108 HU (SD=11.9), respectively. Weight-adjusted dose brought 37% more
      patients into the "ideal" enhancement range of 100-125 HU. CONCLUSION: The use of
      a simple, practical, weight-based look-up table to decide contrast media volumes
      during portal phase liver CT can greatly reduce inter-patient variability
      compared to a fixed-volume technique.

PMID- 21724183
TI  - Automatic brain extraction methods for T1 magnetic resonance images using region
      labeling and morphological operations.
AB  - In this work we propose two brain extraction methods (BEM) that solely depend on
      the brain anatomy and its intensity characteristics. Our methods are simple,
      unsupervised and knowledge based. Using an adaptive intensity thresholding method
      on the magnetic resonance images of head scans, a binary image is obtained. The
      binary image is labeled using the anatomical facts that the scalp is the boundary
      between head and background, and the skull is the boundary separating brain and
      scalp. A run length scheme is applied on the labeled image to get a rough brain
      mask. Morphological operations are then performed to obtain the fine brain on the
      assumption that brain is the largest connected component (LCC). But the LCC
      concept failed to work on some slices where brain is composed of more than one
      connected component. To solve this problem a 3-D approach is introduced in the
      BEM. Experimental results on 61 sets of T1 scans taken from MRI scan center and
      neuroimage web services showed that our methods give better results than the
      popular methods, FSL's Brain Extraction Tool (BET), BrainSuite's Brain Surface
      Extractor (BSE) gives results comparable to that of Model-based Level Sets (MLS)
      and works well even where MLS failed. The average Dice similarity index computed
      using the "Gold standard" and the specificity values are 0.938 and 0.992,
      respectively, which are higher than that for BET, BSE and MLS. The average
      processing time by one of our methods is ~1s/slice, which is smaller than for
      MLS, which is ~4s/slice. One of our methods produces the lowest false positive
      rate of 0.075, which is smaller than that for BSE, BET and MLS. It is independent
      of imaging orientation and works well for slices with abnormal features like
      tumor and lesion in which the existing methods fail in certain cases.

PMID- 21724184
TI  - Mortality in workers employed in pig abattoirs and processing plants.
AB  - OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and
      pork butchers/meatcutters have been little studied for health risks associated
      with employment, in spite of the fact that they are potentially exposed to
      oncogenic and non-oncogenic transmissible agents and chemical carcinogens at
      work. We report here on an update of mortality in 510 workers employed in
      abattoirs and processing plants that almost exclusively handled pigs and pork
      products. METHODS: standardized mortality ratios (SMRs) were estimated for the
      cohort as a whole, and in subgroups defined by race and sex, using the
      corresponding US general population mortality rates for comparison. Study
      subjects were followed up from January 1950 to December 2006, during which time
      45% of them died. RESULTS: mortality was significantly increased overall in the
      cohort. A statistically significant excess of deaths was observed for colon and
      lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI,
      1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also
      observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4
      13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of
      subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3).
      There was a suggestion of an excess of deaths from ischemic heart disease also,
      but the elevated SMR was confined to men and was not statistically significant.
      CONCLUSION: this study confirms the excess occurrence of lung and colon cancers,
      and stroke previously reported in this occupational group. New findings are the
      excess of risk for senile and pre-senile psychotic conditions and pneumonia,
      which together with the excess of colon cancer appear specific for pig/pork
      workers, as they were not evident in much larger studies of workers in abattoirs
      and processing plants handling cattle and sheep. However, caution should be
      exercised in interpreting these findings, since some of them could have occurred
      by chance, resulting from our examination of a large number of causes of death in
      multiple study subgroups. For the moment, the significance of these findings
      remains unknown until they are confirmed in larger studies of adequate
      statistical power. Studies that will take into account possible occupational and
      non-occupational confounding factors are needed.

PMID- 21724185
TI  - Navigation in femoral-shaft fractures--from lab tests to clinical routine.
AB  - INTRODUCTION: This study evaluates the use of a navigation system (BrainLAB,
      Feldkirchen, Germany) to intra-operatively check for correct length, axis and
      rotation in intramedullary nailing of femoral-shaft fractures in an experimental
      setting and in clinical routine. MATERIALS AND METHODS: We tested the navigation
      system in two experimental settings before introducing it into clinical routine.
      In the first experiment, 10 osteotomised model femora were fixed with
      intramedullary nails by using a navigation system. The goal was a locking
      fixation in predefined values for length and rotation. In the second experiment,
      eight examiners assessed values for rotation and length of one femur 10 times to
      examine the accuracy and reproducibility of that determination. Following this,
      we navigated 40 femoral nailing procedures in our department. Preoperatively, we
      assessed values of femur geometry on the contralateral side in a computed
      tomography (CT) scan and reproduced these values intra-operatively on the
      fractured side, guided by the navigation system. During the intervention, we
      recorded the length of the procedure steps and the fluoroscopy time. We verified
      the intra-operative values achieved with the navigation system in a postoperative
      CT scan and documented differences in rotation and length. After the assessment,
      we analysed the data for different findings on femur geometry, fluoroscopy time
      and procedure duration. RESULTS: The experimental evaluation showed a range of +/
      5 degrees  for anteversion differences and +/-2.3 mm for length differences. We
      estimated this accuracy as sufficient to use the system in clinical routine. The
      navigation system was used for 40 fracture fixations. All our criteria for
      restoring femoral geometry could be achieved by navigation guidance in these
      procedures. Setting up the system took on average 33+/-11.5 min. An additional
      fluoroscopy time of 36+/-22 s was needed to acquire the reference X-rays and to
      verify pin placement. The differences between anteversion values assessed in
      intra-operative planning steps on the navigation system and values assessed with
      a postoperative CT were on average 5.4+/-3.5 degrees , whilst femur length
      differed on average by 4+/-4 mm. DISCUSSION: Many authors judge intra-operative
      control of anteversion in femoral-shaft fracture fixation as problematic. Neither
      our experimental navigation assessment nor our clinical navigated evaluation
      showed relevant anteversion differences to a postoperative CT assessment of femur
      geometry. After initial training, guidance by a navigation system achieves
      consistent results in a clinical situation. CONCLUSIONS: The use of a navigation
      system to align axis, length and rotation led to a secure way of avoiding any
      relevant malalignment in complex femur-shaft fractures whilst exposing patients
      to an acceptable amount of additional procedure sequences. Malalignment can be
      avoided by using a navigation system in the operative treatment of femoral-shaft
      fractures and may be integrated into clinical routine in specialised centres.

PMID- 21724186
TI  - What should be the characteristics of the ideal bone graft substitute? Combining
      scaffolds with growth factors and/or stem cells.
AB  - Reconstruction of large bone defects or non-unions resulting from biochemical
      disorders, tumour resections or complicated fractures is still a challenge for
      orthopaedic and trauma surgery. On the one hand, autografts harbour most features
      of ideal bone graft substitutes but on the other hand, they have a lot
      insurmountable disadvantages. An ideal bone graft substitute should be
      biomechanically stable, able to degrade within an appropriate time frame, exhibit
      osteoconductive, osteogenic and osteoinductive properties and provide a
      favourable environment for invading blood vessels and bone forming cells. Whilst
      osteoconductivity of biomaterials for bone tissue engineering strategies can be
      directed by their composition, surface character and internal structure,
      osteoinductive and osteogenic features can be provided by growth factors
      originally participating in fracture healing and/or multipotent mesenchymal
      stromal/stem cells (MSC) capable of rebuilding bone and marrow structures. In
      this review, aspects of the clinical application of the most commonly used growth
      factors for bone repair, the bone morphogenetic proteins (BMPs), and the
      potential use of human MSC for clinical application will be discussed.

PMID- 21724187
TI  - 2D versus 3D transabdominal sonography for the measurement of lower uterine
      segment thickness in women with previous cesarean delivery.
AB  - OBJECTIVE: To evaluate the intermethod reliability of using 3D versus 2D
      transabdominal sonography in the measurement of lower uterine segment (LUS)
      thickness in women with previous cesarean delivery, in addition to determining
      the interobserver reliability of 2D and 3D transabdominal sonography in LUS
      measurement. METHODS: Between February and July 2010 at Queen Mary Hospital, Hong
      Kong, 40 pregnant women with a history of previous cesarean delivery at 36-39
      weeks of pregnancy underwent LUS measurement via 2D and 3D transabdominal
      sonography by 2 observers. The 3D examination was performed on the multiplanar
      display of the longitudinally acquired LUS volume. Inner myometrial thickness
      (MT) and full thickness (FT) were measured at the thinnest portion and
      perpendicular to the contour of the LUS. RESULTS: The 2D and 3D LUS measurements
      obtained by the 2 observers were comparable (intraclass correlation coefficient
      [ICC]: MT, 0.81 and 0.98, respectively; FT, 0.76 and 0.98, respectively). For
      transabdominal LUS measurement, 2D MT provided the best interobserver reliability
      (ICC: 2D MT, 0.95; 2D FT, 0.91; 3D MT, 0.82; 3D FT, 0.77). CONCLUSION: Compared
      with the 2D approach, 3D transabdominal sonography does not seem to improve the
      reliability of LUS measurement. 2D measurement of MT seems to be most reliable
      between different observers.

PMID- 21724188
TI  - Pulse wave propagation in a model human arterial network: Assessment of 1-D visco
      elastic simulations against in vitro measurements.
AB  - The accuracy of the nonlinear one-dimensional (1-D) equations of pressure and
      flow wave propagation in Voigt-type visco-elastic arteries was tested against
      measurements in a well-defined experimental 1:1 replica of the 37 largest conduit
      arteries in the human systemic circulation. The parameters required by the
      numerical algorithm were directly measured in the in vitro setup and no data
      fitting was involved. The inclusion of wall visco-elasticity in the numerical
      model reduced the underdamped high-frequency oscillations obtained using a purely
      elastic tube law, especially in peripheral vessels, which was previously reported
      in this paper [Matthys et al., 2007. Pulse wave propagation in a model human
      arterial network: Assessment of 1-D numerical simulations against in vitro
      measurements. J. Biomech. 40, 3476-3486]. In comparison to the purely elastic
      model, visco-elasticity significantly reduced the average relative root-mean
      square errors between numerical and experimental waveforms over the 70 locations
      measured in the in vitro model: from 3.0% to 2.5% (p<0.012) for pressure and from
      15.7% to 10.8% (p<0.002) for the flow rate. In the frequency domain, average
      relative errors between numerical and experimental amplitudes from the 5th to the
      20th harmonic decreased from 0.7% to 0.5% (p<0.107) for pressure and from 7.0% to
      3.3% (p<10(-6)) for the flow rate. These results provide additional support for
      the use of 1-D reduced modelling to accurately simulate clinically relevant
      problems at a reasonable computational cost.

PMID- 21724189
TI  - Age-related changes in human trabecular bone: Relationship between
      microstructural stress and strain and damage morphology.
AB  - Accumulation of microdamage in aging and disease can cause skeletal fragility and
      is one of several factors contributing to osteoporotic fractures. To better
      understand the role of microdamage in fragility fracture, the mechanisms of bone
      failure must be elucidated on a tissue-level scale where interactions between
      bone matrix properties, the local biomechanical environment, and bone
      architecture are concurrently examined for their contributions to microdamage
      formation. A technique combining histological damage assessment of individual
      trabeculae with linear finite element solutions of trabecular von Mises and
      principal stress and strain was used to compare the damage initiation threshold
      between pre-menopausal (32-37 years, n=3 donors) and post-menopausal (71-80
      years, n=3 donors) femoral cadaveric bone. Strong associations between damage
      morphology and stress and strain parameters were observed in both groups, and an
      age-related decrease in undamaged trabecular von Mises stress was detected. In
      trabeculae from younger donors, the 95% CI for von Mises stress on undamaged
      regions ranged from 50.7-67.9MPa, whereas in trabeculae from older donors,
      stresses were significantly lower (38.7-50.2, p<0.01). Local microarchitectural
      analysis indicated that thinner, rod-like trabeculae oriented along the loading
      axis are more susceptible to severe microdamage formation in older individuals,
      while only rod-like architecture was associated with severe damage in younger
      individuals. This study therefore provides insight into how damage initiation and
      morphology relate to local trabecular microstructure and the associated stresses
      and strains under loading. Furthermore, by comparison of samples from pre- and
      post-menopausal women, the results suggest that trabeculae from younger
      individuals can sustain higher stresses prior to microdamage initiation.

PMID- 21724190
TI  - Intensified extraction of ionized natural products by ion pair centrifugal
      partition extraction.
AB  - The potential of centrifugal partition extraction (CPE) combined with the ion
      pair (IP) extraction mode to simultaneously extract and purify natural ionized
      saponins from licorice is presented in this work. The design of the instrument, a
      new laboratory-scale Fast Centrifugal Partition Extractor (FCPE300((r))), has
      evolved from centrifugal partition chromatography (CPC) columns, but with less
      cells of larger volume. Some hydrodynamic characteristics of the FCPE300((r))
      were highlighted by investigating the retention of the stationary phase under
      different flow rate conditions and for different biphasic solvent systems. A
      method based on the ion-pair extraction mode was developed to extract
      glycyrrhizin (GL), a biologically active ionic saponin naturally present in
      licorice (Glycyrrhiza glabra L., Fabaceae) roots. The extraction of GL was
      performed at a flow rate of 20 mL/min in the descending mode by using the
      biphasic solvent system ethyl acetate/n-butanol/water in the proportions 3/2/5
      (v/v/v). Trioctylmethylammonium with chloride as a counter-ion (Al336((r))) was
      used as the anion extractant in the organic stationary phase and iodide, with
      potassium as counter-ion, was used as the displacer in the aqueous mobile phase.
      From 20 g of a crude extract of licorice roots, 2.2g of GL were recovered after
      70 min, for a total process duration of 90 min. The combination of the
      centrifugal partition extractor with the ion-pair extraction mode (IP-CPE) offers
      promising perspectives for industrial applications in the field of natural
      product isolation or for the fractionation of natural complex mixtures.

PMID- 21724191
TI  - Analyses of sulfonamide antibiotics in meat samples by on-line concentration
      capillary electrochromatography-mass spectrometry.
AB  - In this work, a series of poly(divinylbenzene-alkyl methacrylate) monolithic
      stationary phases, which were prepared by single step in situ polymerization of
      divinylbenzene and various alkyl methacrylates (butyl-, octyl-, lauryl- or
      stearyl methacrylate), were developed as separation columns of nine common
      sulfonamide antibiotics for capillary electrochromatography (CEC) coupled to mass
      spectrometry (MS). Results indicated that the sulfonamide's retention became weak
      with increased carbon chain length of alkyl methacrylate monomer (for example,
      t(R)=68 min and 21 min for butyl- and lauryl methacrylate, respectively). Among
      them, the poly(divinylbenzene-octyl methacrylate) (poly(DVB-OMA)) monolith was
      regarded as the optimal separation column as this provided better resolution
      within the shortest retention time. Moreover, the cross-sectional roughness of
      the monolithic column-end, that was used to couple to the ESI interface, strongly
      influenced the electrospray stability in the CEC-MS. Before the column was
      connected to the ESI-MS, a simple polishing was done to reduce the roughness of
      the column end that resulted to a great improvement in the signal stability. The
      relative standard deviations (RSDs) of the peak areas for the unpolished and
      polished ends of the poly(DVB-OMA) columns (n=5) were in the range of 46.1-60.2%
      and 8.9-16.4%, respectively. Furthermore, optimization of the mobile phase
      composition and the gradient elution strategy successfully determined the
      sulfonamide antibiotics in meat samples with as low as 10 MUg/L level.

PMID- 21724192
TI  - Solid-state synthesis of embedded single-crystal metal oxide and phosphate
      nanoparticles and in situ crystallization.
AB  - A new solid state organometallic route to embedded nanoparticle-containing
      inorganic materials is shown, through pyrolysis of metal-containing derivatives
      of cyclotriphosphazenes. Pyrolysis in air and at 800  degrees C of new molecular
      precursors gives individual single-crystal nanoparticles of SiP(2)O(7), TiO(2),
      P(4)O(7,) WP(2)O(7) and SiO(2), depending on the precursor used. High resolution
      transmission electron microscopy investigations reveal, in most cases, perfect
      single crystals of metal oxides and the first nanostructures of negative thermal
      expansion metal phosphates with diameters in the range 2-6 nm for all products.
      While all nanoparticles are new by this method, WP(2)O(7) and SiP(2)O(7)
      nanoparticles are reported for the first time. In situ recrystallization
      formation of nanocrystals of SiP(2)O(7) was also observed due to electron beam
      induced reactions during measurements of the nanoparticulate pyrolytic products
      SiO(2) and P(4)O(7). The possible mechanism for the formation of the
      nanoparticles at much lower temperatures than their bulk counterparts in both
      cases is discussed. Degrees of stabilization from the formation of P(4)O(7)
      affects the nanocrystalline products: nanoparticles are observed for WP(2)O(7),
      with coalescing crystallization occurring for the amorphous host in which
      SiP(2)O(7) crystals form as a solid within a solid. The approach allows the
      simple formation of multimetallic, monometallic, metal-oxide and metal phosphate
      nanocrystals embedded in an amorphous dielectric. The method and can be extended
      to nearly any metal capable of successful coordination as an organometallic to
      allow embedded nanoparticle layers and features to be deposited or written on
      surfaces for application as high mobility pyrophosphate lithium-ion cathode
      materials, catalysis and nanocrystal embedded dielectric layers.

PMID- 21724193
TI  - Intensive voice treatment (LSVT(r)LOUD) for Parkinson's disease following deep
      brain stimulation of the subthalamic nucleus.
AB  - PURPOSE: Intensive voice therapy (LSVT((r))LOUD) can effectively manage voice and
      speech symptoms associated with idiopathic Parkinson disease (PD). This small
      group study evaluated voice and speech in individuals with and without deep brain
      stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to
      determine whether outcomes for surgical subjects were comparable to non-surgical
      cohorts. METHODS: Eight subjects with PD (four with STN-DBS and four without)
      received LSVT LOUD four times a week for four weeks. Four additional subjects
      with PD remained untreated. Voice intensity (SPL), Vowel Articulation Index
      (VAI), the Voice Handicap Index (VHI), and a structured interview were evaluated
      before and after treatment and again six months later. RESULTS: Both treated
      groups showed significant increases in SPL from pre to post and six-month follow
      up. VAI was significantly higher for the treated groups compared to the untreated
      subjects at follow up. Several treated individuals had significant clinical
      improvement in VHI scores, particularly within the LSVT-DBS group. Treated
      individuals reported improvements in voice and speech in structured interviews;
      however, answers suggest more variable long-term maintenance within the LSVT-DBS
      group. The untreated group exhibited no significant changes in any measure
      throughout the study. CONCLUSIONS: Results support LSVT LOUD for treating voice
      and speech in individuals with PD following STN-DBS surgery. However,
      modifications may be required to maintain functional improvements. LEARNING
      OUTCOMES: As a result of this activity, the participant will be able to (1)
      describe how deep brain stimulation of the subthalamic nucleus may affect voice
      and speech in Parkinson disease; (2) describe the effects of intensive voice
      therapy (LSVT((r))LOUD) on people with PD both with and without STN-DBS; (3)
      describe how individuals with STN-DBS maintained treatment effects over time.

PMID- 21724194
TI  - Minimally invasive aortic valve replacement via right anterior minithoracotomy:
      early outcomes and midterm follow-up.

PMID- 21724195
TI  - The impact of adjuvant brachytherapy with sublobar resection on pulmonary
      function and dyspnea in high-risk patients with operable disease: preliminary
      results from the American College of Surgeons Oncology Group Z4032 trial.
AB  - BACKGROUND: Z4032 was a randomized study conducted by the American College of
      Surgeons Oncology Group comparing sublobar resection alone versus sublobar
      resection with brachytherapy for high-risk operable patients with non-small cell
      lung cancer (NSCLC). This evaluates early impact of adjuvant brachytherapy on
      pulmonary function tests, dyspnea, and perioperative (30-day) respiratory
      complications in this impaired patient population. METHODS: Eligible patients
      with stage I NSCLC tumors 3 cm or smaller were randomly allocated to undergo
      sublobar resection with (SRB group) or without (SR group) brachytherapy. Outcomes
      measured included the percentage predicted forced expiratory volume in 1 second
      (FEV1%), percentage predicted carbon monoxide diffusion capacity (DLCO%), and
      dyspnea score per the University of California San Diego Shortness of Breath
      Questionnaire. Pulmonary morbidity was assessed per the Common Terminology
      Criteria for Adverse Events version 3.0. Outcomes were measured at baseline and 3
      months. A 10% change in pulmonary function test or 10-point change in dyspnea
      score was deemed clinically meaningful. RESULTS: Z4032 permanently closed to
      patient accrual in January 2010 at 224 patients. At 3-month follow-up, pulmonary
      function data are currently available for 148 (74 SR and 74 SRB) patients
      described in this report. There were no differences in baseline characteristics
      between arms. In the SR arm, 9 patients (12%) reported grade 3 respiratory
      adverse events, compared with 12 (16%) in the SRB arm (P = .49). There was no
      significant change in percentage change in DLCO% or dyspnea score from baseline
      to 3 months within either arm. In the case of FEV1%, percentage change from
      baseline to 3 months was significant within the SR arm (P = .03), with patients
      reporting improvement in FEV1% at month 3. Multivariable regression analysis
      (adjusted for baseline values) showed no significant impact of treatment arm,
      tumor location (upper vs other lobe), or surgical approach (video-assisted
      thoracoscopic surgery vs thoracotomy) on 3-month FEV1%, DLCO%, and dyspnea score.
      There was no significant difference in incidence of clinically meaningful (10%
      pulmonary function or 10-point dyspnea score change) change between arms. Twenty
      two percent of patients with lower-lobe tumors and 9% with upper-lobe tumors
      demonstrated 10% decline in FEV1% (odds ratio, 2.79; 95 confidence interval, 1.07
      7.25; P = .04). CONCLUSIONS: Adjuvant intraoperative brachytherapy in conjunction
      with sublobar resection did not significantly worsen pulmonary function or
      dyspnea at 3 months in a high-risk population with NSCLC, nor was it associated
      with increased perioperative pulmonary adverse events. Lower-lobe resection was
      the only factor significantly associated with clinically meaningful decline in
      FEV1%.

PMID- 21724196
TI  - Surgical management of aortic root abscess: a 13-year experience in 172 patients
      with 100% follow-up.
AB  - OBJECTIVE: The study objective was to evaluate the outcomes of surgery for active
      infective endocarditis with aortic root abscess formation. METHODS: Between July
      1996 and June 2009, 1161 patients underwent operation for aortic valve
      endocarditis, of whom 172 had aortic root abscess. The infected valve was native
      in 96 patients and prosthetic in 76 patients. Patients' mean age (+/- standard
      deviation) and logistic EuroSCORE-predicted risk of mortality were 62 +/- 13
      years and 23.1% +/- 26%, respectively. Surgery was emergent in 96 patients (58%).
      The abscess involved the aortic annulus in 90 patients (52%), the intervalvular
      fibrous body in 81 patients (47%), and the mitral annulus in 21 patients (12%).
      Surgery consisted of radical resection of the abscess, reconstruction of the
      annulus with patches, and valve replacement. Estimated mean follow-up was 4.0 +/-
      0.3 years (range, 0-8.2 years). RESULTS: Thirty-day mortality was 25% (n = 43)
      (prosthetic valve endocarditis vs native valve endocarditis, 35.5% vs 16.7%, P =
      .005). Independent predictors of mortality were sepsis (odds ratio [OR], 3.6; 95%
      confidence interval [CI], 1.2-10.7), renal insufficiency (OR, 3.3; 95% CI, 1.1
      9.5), concomitant coronary artery bypass grafting (OR, 2.8; 95% CI, 1.1-7.0), and
      prosthetic valve endocarditis (OR, 2.4; 95% CI, 1.1-5.6). Survival at 1 and 5
      years was 55% +/- 4% and 50% +/- 4%, respectively, and predicted by concomitant
      mitral endocarditis (OR, 3.2; 95% CI, 1.3-8.2), sepsis (OR, 2.7; 95% CI, 1.6
      4.5), renal insufficiency (OR, 1.9; 95% CI, 1.1-3.4), and age (OR, 1.05; 95% CI,
      1.02-1.07). Endocarditis recurred in 15 patients (8.7%) at a mean of 1.8 +/- 2.4
      years postoperatively (39 days to 6 years). CONCLUSIONS: The surgical treatment
      of aortic root abscess remains a challenge with relatively high perioperative
      morbidity and mortality, although long-term survival is satisfactory.

PMID- 21724197
TI  - A phase 2 prospective, randomized, double-blind trial comparing the effects of
      tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery
      with cardiopulmonary bypass (CONSERV-2 Trial).
AB  - OBJECTIVE: Ecallantide is a recombinant peptide in the same class as aprotinin
      that inhibits plasma kallikrein, a major component of the contact coagulation and
      inflammatory cascades. Therefore, ecallantide was expected to reduce blood loss
      associated with cardiac surgery requiring cardiopulmonary bypass. METHODS: This
      prospective multinational, randomized, double-blind trial enrolled patients
      undergoing cardiac surgery using cardiopulmonary bypass for procedures associated
      with a high risk of bleeding. Patients were randomly assigned to ecallantide (n =
      109) or tranexamic acid (high dose, n = 24; low dose, n = 85). Efficacy was
      assessed from the volume of packed red blood cells administered within the first
      12 hours after surgery. RESULTS: The study was terminated early after the
      independent data safety and monitoring board observed a statistically
      significantly higher 30-day mortality in the ecallantide group (12%) than in the
      tranexamic acid groups (4%, P = .041). Patients receiving ecallantide received
      more packed red blood cells within 12 hours of surgery than tranexamic acid
      treated patients: median = 900 mL (95% confidence interval, 600-1070) versus 300
      mL (95% confidence interval, 0-523) (P < .001). Similar differences were seen at
      24 hours and at discharge. Patients treated with the higher tranexamic acid dose
      received less packed red blood cells, 0 mL (95% confidence interval, 280-600),
      than the group treated with the lower dose, 400 mL (95% confidence interval, 0
      400) (P = .008). No deaths occurred in the higher dose tranexamic acid group.
      CONCLUSIONS: Ecallantide was less effective at reducing perioperative blood loss
      than tranexamic acid. High-dose tranexamic acid was more effective than the low
      dose in reducing blood loss.

PMID- 21724198
TI  - Transpulmonary arterial repair of type 1 ventricular septal defect will induce
      pulmonary regurgitation: appraisal of subpulmonic approach.
AB  - OBJECTIVE: A transpulmonary arterial approach to repair type I ventricular septal
      defect is the standard. However, the possible adverse effect on the pulmonary
      valve by this technique has not been investigated. METHODS: A retrospective study
      reviewing type I ventricular septal defect repair from January 1991 to May 2010
      was conducted. Of the 142 cases, the ventricular septal defect was repaired via
      the transpulmonary arterial route in 77 patients (54.2%, PA group) and via the
      subpulmonic route in 65 patients (45.8%, SP group). All patients received serial
      annual transthoracic color Doppler echocardiographic evaluation of pulmonary
      valve function. RESULTS: The age at operation ranged from 1.2 to 272 months
      (median, 35.0 months; mean, 50.4 months). The mean follow-up period was 96.2
      months (range, 2-234 months). Between the PA and SP groups, there was no
      significant difference in age, body weight, ventricular septal defect size, left
      to right shunt amount, mean pulmonary arterial pressure, and preoperative
      pulmonary stenosis or regurgitation. Postoperatively, there was no significant
      difference in the ejection fraction or incidence of residual ventricular septal
      defect, right bundle branch block, and pulmonary stenosis. However, the incidence
      of postoperative pulmonary regurgitation of more than moderate and the total
      scale of postoperative pulmonary regurgitation were both significantly higher in
      the PA group (16.9% vs 4.6% and 1.7 +/- 0.1 vs 1.4 +/- 0.1, P = .031 and .019,
      respectively). CONCLUSIONS: Although the transpulmonary arterial approach for
      type I ventricular septal defect repair has been advocated for decades,
      considering the adverse effect on pulmonary valve competency, the subpulmonic
      approach may be an alternative.

PMID- 21724199
TI  - Surgical mentorship.

PMID- 21724200
TI  - Late left atrial thrombosis of an Amplatzer patent foramen ovale occluder.

PMID- 21724201
TI  - Aneurysmal right coronary with fistula to the coronary sinus combined with severe
      stenosis of the left anterior descending artery: a snake on the heart.

PMID- 21724203
TI  - Management of immune dysfunction after adult cardiac surgery.
AB  - OBJECTIVE: Pulmonary dysfunction/multiorgan failure syndrome is an important
      cause of mortality and morbidity after cardiac operations. In this series,
      results of immune augmentation were assessed in patients experiencing pulmonary
      dysfunction/multiorgan failure syndrome after cardiac surgery. METHODS: Since
      2002, 44 consecutive patients with primary antibiotic-refractory pulmonary
      dysfunction/multiorgan failure syndrome were treated with intravenous
      immunoglobulin (0.3 g/kg * 5 days; 1.5 g/kg total dose). Thirty patients had
      undergone complex valve or aortic surgery, and 14 patients had coronary bypass.
      Median age was 66 years, and risk profiles were especially high preoperatively.
      Clinical variables were assessed for 3 days prior (-3) to beginning intravenous
      immunoglobulin (on day 0) and for 5 days afterward (+5). A postoperative
      morbidity index was generated as a weighted sum of all relevant clinical
      variables. By using each patient as his or her own control, the therapeutic
      effect of intravenous immunoglobulin was assessed with linear regression of
      postoperative morbidity index over time with a spline and a knot at day 0,
      coincident with beginning intravenous immunoglobulin. RESULTS: At day 0, all
      patients were deteriorating clinically and refractory to major antibiotics.
      Overall morbidity was high, and immunoglobulin-G levels, obtained in the last 14
      patients, were consistently low. By using linear regression of postoperative
      morbidity index over time, intravenous immunoglobulin administration was
      associated with significant improvement in clinical status (P < .0001). A total
      of 42 of 44 patients (95%) recovered uneventfully to hospital discharge. No
      significant complications of intravenous immunoglobulin therapy occurred.
      CONCLUSIONS: This experience suggests that management of immune dysfunction with
      intravenous immunoglobulin is safe and effective for treatment of primary
      pulmonary dysfunction/multiorgan failure syndrome after cardiac surgery. Expanded
      application seems indicated.

PMID- 21724204
TI  - Transapical aortic valve implantation at 3 years.
AB  - OBJECTIVE: Our objective was to analyze the results of transapical aortic valve
      implantation in high-risk patients with aortic stenosis at up to 3 years after
      the procedure. METHODS: A total of 299 patients underwent transapical aortic
      valve implantation from February 2006 until January 2010 using the Edwards SAPIEN
      transcatheter xenograft. Mean patient age was 82 +/- 6 years and 70% were female.
      Logistic EuroSCORE and Society of Thoracic Surgeons score predicted risks for
      mortality were 31% +/- 16% and 12% +/- 8%, respectively. All patients were
      treated in a hybrid operative theater by a team of anesthetists, cardiologists
      and cardiac surgeons. RESULTS: Successful valve implantation was performed in all
      patients. Transapical aortic valve implantation was uneventful in 267 patients
      (89.3%), whereas 32 patients (10.7%) required additional interventions. Such
      interventions included cardiopulmonary bypass support in 18, implantation of a
      second SAPIEN valve in 15, coronary intervention in 9, conversion to conventional
      surgery in 6, and annulus perforation in 3 patients (not mutually exclusive).
      Intraprocedural stroke was not observed in any patient, although 2 (0.7%)
      patients had a delayed stroke during their hospital stay. Overall survival was
      91% at 30 days, 73% at 1 year, 68% at 2 years, and 58% at 3 years. CONCLUSIONS:
      Transapical aortic valve implantation can be performed with good outcomes in high
      risk patients with aortic stenosis. Perioperative complications occur in
      approximately 10% of patients, and a variety of interventions are required for
      these events. We believe a team approach is therefore essential for the success
      of transapical aortic valve implantation.

PMID- 21724205
TI  - Lysosomal and lipid-associated parameters in the livers of three species of
      arctic seabird chicks: species differences and relationships with contaminant
      levels.
AB  - Lysosomal membrane stability, lipofuscin (LF), malondialdehyde (MDA), neutral
      lipid (NL) levels, as well as halogenated organic compounds (HOCs), Cr, Cd, Pb
      and Fe concentrations were analyzed in liver of black-legged kittiwake (BK),
      herring gull (HG), and northern fulmar (NF) chicks. There were significant
      species differences in the levels of NL, LF and lysosomal membrane stability.
      These parameters were not associated with the respective HOC concentrations. LF
      accumulation was associated with increasing Cr, Cd and Pb concentrations. HG
      presented the lowest lysosomal membrane stability and the highest. LF and NL
      levels, which indicated impaired lysosomes in HG compared to NF and BK. Lipid
      peroxidation was associated with HOC and Fe2+ levels. Specific HOCs showed
      positive and significant correlations with MDA levels in HG. The study indicates
      that contaminant exposure can affect lysosomal and lipid associated parameters in
      seabird chicks even at low exposure levels. These parameters may be suitable
      markers of contaminant induced stress in arctic seabirds.

PMID- 21724206
TI  - The impact of the herbicide atrazine on growth and photosynthesis of seagrass,
      Zostera marina (L.), seedlings.
AB  - The impact of the widely used herbicide atrazine on seedling growth and
      photosynthesis of eelgrass was determined. The long-term impact of the herbicide
      atrazine (1, 10 and 100 MUg/L) on growth of eelgrass Zostera marina (L.)
      seedlings, maintained in outdoor aquaria, was monitored over 4 weeks. Exposure to
      10 MUg/L atrazine resulted in significantly lower plant fresh weight and total
      chlorophyll concentration and up to 86.67% mortality at the 100 MUg/L
      concentration. Short-term photosynthetic stress on eelgrass seedlings was
      determined and compared with adult eelgrass using chlorophyll fluorescence. The
      effective quantum yield in eelgrass seedlings was significantly depressed at all
      atrazine concentrations (2, 4, 8, 16, 32 and 64 MUg/L) even within 2 h and
      remained at a lower level than for adult plants for each concentration. These
      results indicate that atrazine presents a potential threat to seagrass seedling
      functioning and that the impact is much higher than for adult plants.

PMID- 21724207
TI  - Detection and isolation of p-nitrophenol-lowering bacteria from intestine of
      marine fishes caught in Japanese waters.
AB  - To determine the existence of p-nitrophenol (PNP)-lowering bacteria in intestine
      of Japanese coastal fish, the gastro-intestinal contents were incubated in Brain
      Heart Infusion (BHI) broth and minimal medium (MM) broths containing 1 mmol/L PNP
      at 30  degrees C for 7 days. Among 26 samples of 19 fish species, 17 samples
      showed a decrease in PNP of 0.5-0.8 mmol/L in BHI broth, but no decrease was
      shown in MM broth. Eighteen PNP-lowering bacterial strains were isolated from
      four fishes. All of the strains were identified as Lactococcus lactis subsp.
      lactis. Three L. lactis strains JS1-3 isolated from Japanese seabass Lateolabrax
      japonicus showed the highest PNP-lowering activity (0.44 mmol/L). Optimum
      temperature and pH for the growth and PNP decreasing corresponded with the marine
      environment. These results suggested that marine fishes have PNP decreasing
      bacteria in their intestine. These bacteria might protect host fish from
      toxicities of PNP and PNP related compounds.

PMID- 21724208
TI  - Considering intersections of race and gender in interventions that address US
      men's health disparities.
AB  - Although gender, racial and ethnic differences in health in the USA are well
      documented, it is less clear how race and gender intersect to produce large and
      consistently poor health outcomes for men of colour, particularly Black American
      men. This paper will illustrate how race and gender intersect at multiple levels
      to shape men's health and health behaviours, and function as fundamental social
      determinants of health. The paper will conclude by discussing the need to attend
      to the role of male gender in pathways and processes underlying racial health
      disparities, and the challenges of developing health promotion interventions for
      Black American men.

PMID- 21724209
TI  - [Multidetector computed tomography as the first diagnostic option for acute lower
      digestive tract bleeding in the Emergency Department].
AB  - The wide availability, speed, safety, and diagnostic accuracy of multidetector
      computed tomography (MDCT) make it the first-line diagnostic tool in the study of
      acute bleeding of the lower digestive tract. The use of MDCT after the initial
      stabilization of the patient makes it possible to identify active bleeding and to
      determine its origin and possible cause, even when bleeding has stopped. MDCT
      provides information that is key to selecting the most appropriate treatment
      option: colonoscopy, embolization, surgery, or clinical follow-up. MDCT orients
      the surgical or endovascular intervention, minimizing the time, risks, and doses
      of radiation and of contrast agents involved in the intervention and avoiding
      "blind" resections associated with greater morbimortality. Although the active
      presence of radiologists in the Emergency Department involves some disadvantages
      in scheduling, it also places radiologists in a privileged position in their
      relations with other techniques and professionals involved in the management of
      acute lower digestive tract bleeding.

PMID- 21724210
TI  - [Contained chronic rupture and acute occlusion of an abdominal aortic aneurysm].

PMID- 21724211
TI  - [Isolated spontaneous dissection of visceral arteries].
AB  - We present the cases of two men with isolated spontaneous dissection of visceral
      arteries diagnosed by multidetector CT. In the first patient, dissection of the
      celiac trunk was associated with periarterial changes. In the second patient,
      dissection of the superior mesenteric artery was associated with stenosis at the
      root of the celiac trunk. Both patients presented with acute pain, which was more
      intense and longer lasting in the first patient. Aortic dissection was suspected
      clinically in both patients. Both dissections were short and had patent saccular
      false lumens and reduced caliber of the true lumens. This morphological type is
      one of the most uncommon within this rare entity. However, in recent years, the
      number of cases published is rising. This suggests that this entity may have been
      underdiagnosed before the widespread use of multidetector CT. We discuss the two
      morphological classifications of dissection of the visceral arteries and the need
      to adapt therapeutic management to the particular circumstances of each case. 

PMID- 21724213
TI  - [Endolymphatic sac carcinoma: a case report].

PMID- 21724215
TI  - [Venous thrombosis as a complication of L-asparaginase treatment in a child].

PMID- 21724214
TI  - [Middle aortic syndrome: a report of three pediatric cases].
AB  - The middle aortic syndrome (MAS) is caused by stenosis of the abdominal aorta,
      often accompanied by concomitant stenosis of the renal or visceral arteries.
      Although MAS is uncommon (0.5-2%), it is an important cause of hypertension in
      children and adolescents. It is thought to originate in a failure of the two
      dorsal aortas to fuse during embryological development, and a high percentage of
      cases are idiopathic. MAS affects the segment of the aorta between the renal
      arteries in 54% of cases. Clinically, it courses with symptomatic or asymptomatic
      arterial hypertension. On physical examination, findings include an abdominal
      bruit, diminished or absent femoral pulses, and a difference between the arterial
      pressure of the upper and lower limbs. Angiography is the technique of choice,
      although noninvasive MR angiography and CT angiography have similar diagnostic
      accuracy. Ultrasonography is the primary screening technique. Medical treatment
      consists of a combination of different antihypertensives. Surgical treatment can
      be curative. 

PMID- 21724216
TI  - Temporal pattern of locomotor activity recuperation after administration of
      propofol in Japanese quail (Coturnix coturnix japonica).
AB  - The present study evaluates the organization and complexity of the temporal
      pattern of locomotion after an acute administration of propofol in Japanese quail
      by using traditional and fractal analysis. Birds were administered with propofol
      0, 10, 20, 40 or 80 mg/kg. Ten min after administration, they were placed in an
      open-field apparatus and their locomotor activity was recorded during 45 min at a
      resolution of 0.5 s. A significant dose dependant increase in the latency to
      initiate ambulation was observed for doses of 20, 40 and 80 mg/kg when compared
      to the control group. A rapid recuperation of normal locomotor activity was
      observed after sedation with 20 mg/kg. Birds administered with propofol 40 mg/kg
      showed signs of recuperation of normal locomotion after 30 and 40 min (males and
      females, respectively) of propofol administration, that was not observed in quail
      treated with propofol 80 mg/kg. Our results suggest that depending on the dose,
      propofol administration in quail may allow full locomotor recovery of a
      sedative/anesthetic dose as early as 30 min post-administration.

PMID- 21724217
TI  - Molecular cloning, in vitro expression and functional characterization of canine
      ADAMTS13.
AB  - A disintegrin and metalloproteinase with thrombospondin type 1 motifs, number 13
      (ADAMTS13) is a plasma zinc metalloprotease also known as von Willebrand factor
      (VWF)-cleaving protease. Deficiency of ADAMTS13 activity is known to cause
      thrombotic thrombocytopenic purpura (TTP) in humans. We isolated the canine
      ADAMTS13 cDNA, which encodes 1502 amino acids, and expressed the recombinant
      protein to evaluate VWF-cleaving ability. Although the propeptide domain was
      longer and the TSP1 repeat domain was shorter than those in other species, the
      overall structures were similar to human and mouse ADAMTS13. Recombinant canine
      ADAMTS13 cleaved the 250-kDa VWF monomer into two fragments of 150 kDa and 120
      kDa. Furthermore, high molecular weight VWF multimers were abolished based on the
      activity of ADAMTS13. These results could facilitate research into hemostatic
      disorders such as TTP in dogs.

PMID- 21724218
TI  - Effect of moderate Cu supplementation on serum metabolites, enzymes and redox
      state in feedlot calves.
AB  - The aim of this investigation was to evaluate whether, in the nutritional
      management of commercial feedlots, copper (Cu) supplementation is justified to
      maintain the physiological requirements. This study compared beef calves fed
      concentrates with an average Cu basal content of 5 and 8 mg/kg in growing and
      finishing periods (10 animals) or supplemented with 15 mg/kg for each phase (20
      animals) as regards production indices, metabolic parameters [glucose,
      nonesterified fatty acids (NEFA), cholesterol, serum urea nitrogen (SUN),
      creatinine, total serum protein (TSP), albumin, aspartate transaminase (AST) and
      gamma-glutamyl transferase (GGT)] and markers of oxidative stress (reactive
      oxygen species (ROS) and serum antioxidant capacity (SAC)). Data were recorded at
      ages 12, 24 and 36 weeks. In general, Cu supplementation was neither detrimental
      nor beneficial for animal health and performance, and the levels of the measured
      metabolites and enzymes were within their normal ranges stated for feedlot with
      the same management during the whole study. However, in keeping with reported
      higher hepatic Cu levels at slaughter, animals on supplemented feed had higher
      GGT activities at the end of the finishing stage, although the difference was not
      statistically significant. On the other hand, lower SAC levels at the end of the
      growing period in the supplemented group suggest the possibility of a positive
      effect of Cu supplementation on redox state. Further research is necessary to
      clarify the potential role of Cu in limiting the ROS production associated with
      fattening diets, and to evaluate the hepatobiliary consequences of
      supplementation, including hepatic Cu accumulation.

PMID- 21724219
TI  - Retention and attrition during the preparation phase and after start of
      antiretroviral treatment in Thyolo, Malawi, and Kibera, Kenya: implications for
      programmes?
AB  - Among adults eligible for antiretroviral therapy (ART) in Thyolo (rural Malawi)
      and Kibera (Nairobi, Kenya), this study (a) reports on retention and attrition
      during the preparation phase and after starting ART and (b) identifies risk
      factors associated with attrition. 'Retention' implies being alive and on follow
      up, whilst 'attrition' implies loss to follow-up, death or stopping treatment (if
      on ART). There were 11,309 ART-eligible patients from Malawi and 3633 from Kenya,
      of whom 8421 (74%) and 2792 (77%), respectively, went through the preparation
      phase and started ART. In Malawi, 2649 patients (23%) were lost to attrition in
      the preparation phase and 2189 (26%) after starting ART. Similarly, in Kenya 546
      patients (15%) were lost to attrition in the ART preparation phase and 647 (23%)
      while on ART. Overall programme attrition was 43% (4838/11,309) for Malawi and
      33% (1193/3633) for Kenya. Restricting cohort evaluation to 'on ART' (as is
      usually done) underestimates overall programme attrition by 38% in Malawi and 36%
      in Kenya. Risk factors associated with attrition in the preparation phase
      included male sex, age <35 years, advanced HIV/AIDS disease and increasing
      malnutrition. Considerable attrition occurs during the preparation phase of ART,
      and programme evaluations confined to on-treatment analysis significantly
      underestimate attrition. This has important operational implications, which are
      discussed here.

PMID- 21724220
TI  - High nonlinearities in Langevin transducer: a comprehensive model.
AB  - The design and simulation of power transducers are difficult since piezoelectric,
      dielectric and elastic properties of ferroelectric materials differ from linear
      behavior when driven at large levels. This paper is devoted to modeling of a
      resonant power transducer at a high level of dynamic mechanical stress. The power
      transducer is subjected to a sine electrical field E of varying frequency which
      was considered as the excitation of the transducer. The mechanical equation of
      the piezoelectric element is written using electrostriction. The dielectric part
      is written as a nonlinear function of an equivalent electric field including
      stress influence (scaling relationship between electric field and mechanical
      stress). Using various simulations, we show then that typical resonance
      nonlinearities are obtained, such as jump phenomenon of transducer speed
      amplitude and phase, resonance peak that become asymmetric, and diminution of
      mechanical quality factor. As a consequence, we state that those typical
      nonlinearities are only due to dielectric nonlinearities, in good correlation
      with typical ferroelectric behavior. Moreover, this demonstrates the usefulness
      of scaling relationships in ferroelectrics, which explain static depoling under
      stress and butterfly strain hysteresis loop. The same scaling law gives here
      several nonlinearities for resonant transducers as well.

PMID- 21724221
TI  - Characterization of bottom sediments in lakes using hydroacoustic methods and
      comparison with laboratory measurements.
AB  - The acoustical properties of bottom sediments in two lakes were shown to be
      strongly correlated with clay content, organic C and total N concentrations, and
      other important sediment properties. The fractal dimension of the bottom echo was
      more strongly correlated with sediment physical and chemical properties than
      energy-based measures. The fractal dimension was also related to rates of PO4-P
      and NH4-N release from intact sediment cores and sediment oxygen demand.
      Measurements made at 430-kHz were more sensitive to differences in sediment
      properties than 201- or 38-kHz. Hydroacoustic measurements allow rapid assessment
      of properties important in lake restoration and water resource management.

PMID- 21724222
TI  - Enhanced trace phosphate removal from water by zirconium(IV) loaded fibrous
      adsorbent.
AB  - This study was investigated for the trace phosphate removal at high feed flow
      rate by ligand exchange fibrous adsorbent. The zirconium(IV) loaded bifunctional
      fibers containing both phosphonate and sulfonate were used as a highly selective
      ligand exchange adsorbent for trace phosphate removal from water. The precursory
      fiber of the bifunctional fibers was co-grafted by polymerization of
      chloromethylstyrene and styrene onto polyethylene coated polypropylene fiber and
      then bifunctional fibers were prepared by Arbusov reaction followed by
      phosphorylation and sulfonation. Phosphate adsorption experimental work was
      carried out in column approach. Phosphate adsorption increased with decreasing
      the pH of feed solutions. An increase in the feeds flow rate brings a decrease in
      both breakthrough capacity and total adsorption. The effect of competing anions
      on phosphate adsorption systems was investigated. The experimental findings
      reveal that the phosphate adsorption was not affected in the presence of
      competing anions such as chloride and sulfate despite the enhancement of the
      breakthrough points and total adsorption. Due to high selectivity to phosphate
      species, low concentration level of phosphate (0.22 mg/L) was removed at high
      feed flow rate of 450 h(-1) in space velocity. The adsorbed phosphate on the
      Zr(IV) loaded fibrous column was quantitatively eluted with 0.1 M NaOH solution
      and then the column was regenerated by 0.5M H2SO4 for the next adsorption
      operation. During many adsorption-elution-regeneration cycles, no measurable
      Zr(IV) was found in the column effluents. Therefore, the Zr(IV) loaded
      bifunctional fibrous adsorbent is to be an effective means to treat wastewater to
      prevent eutrophication in the receiving water bodies for long time without any
      deterioration.

PMID- 21724223
TI  - Sediment analysis to support the recent glacial origin of DDT pollution in Lake
      Iseo (Northern Italy).
AB  - In the present study, a depth-related distribution of Persistent Organic
      Pollutants (POPs) in sediments of Lake Iseo, one of the major southern Alpine
      Italian lakes, is reported in order to further test the hypothesis of melting
      Alpine glaciers as a secondary source of contamination. In a previous paper, a
      "glacier contamination hypothesis" was suggested to explain the unexpected
      contamination of the biota of Lake Iseo, mainly fed by the Alpine melting ice.
      The sediment core analyses covered around the last 50 years. The organic matter
      profile evaluated as a Loss-On-Ignition percentage indicated transition of the
      basin from an oligotrophic to a mesotrophic status at around the early 1970s, but
      there was no evidence of the shift to eutrophy in the 1980s. Among DDTs, pp'DDE
      was the predominant metabolite, accounting on average for 79.4% of the total DDT
      concentrations and ranging from 6.4 to 447.5 ng g(-1)d.w. PCBs ranged from 5.0 to
      163.7 ng g(-1)d.w. The maximum PCB concentrations were found in sediment layers
      corresponding to the 1970s when the highest production and use of these compounds
      occurred in Italy. In contrast, concentrations of DDTs showed a sharp increase
      from the early 1990s, long after their agricultural use was banned in Italy. This
      delayed pollution provides support for the hypothesis that the recent retreat of
      glaciers represents a secondary pollution source for old pesticides that were
      stored in the ice at the time of their use in agriculture.

PMID- 21724224
TI  - Preparation and X-ray structural characterization of further stereoisomers of
      1,2,5,6,9,10-hexabromocyclododecane.
AB  - Technical 1,2,5,6,9,10-hexabromocyclododecane (HBCD) consists largely of three
      diastereomers (alpha-, beta-, and gamma-HBCD) produced by the trans addition of
      bromine to cis,trans,trans-cyclododeca-1,5,9-triene (CDT). However, another seven
      diastereomers are theoretically possible and may be produced by trans addition of
      bromine across the double bonds of the other three isomers of 1,5,9-CDT. There
      are indications that small amounts of the minor HBCD isomers may be present in
      commercial HBCD mixtures or in products containing this brominated flame
      retardant (BFR). Such minor components may indeed derive from traces of other
      1,5,9-CDTs in the cis, trans, trans starting material, however their formation
      may also be possible through isomerizations during the processing of this BFR or
      by bioisomerization subsequent to its release into the environment. Two of the
      seven additional diastereomers (delta- and epsilon-HBCD) were synthesized
      previously from trans,trans,trans-CDT. We now report the preparation of the
      remaining five diastereomers, zeta-, eta-, and theta-HBCD from cis,cis,trans-CDT
      and iota- and kappa-HBCD from cis,cis,cis-CDT, and their characterization by (1)H
      NMR spectroscopy and X-ray crystallography. The availability of these further
      diastereomers of HBCDshould aid in determining if the minor isomers are present
      in commercial samples of this BFR, in products containing HBCDs, or in
      environmental samples. We have also carried out an X-ray crystal structure
      determination on epsilon-HBCD, so that crystal structures are now available for
      all 10 HBCD diastereomers.

PMID- 21724225
TI  - Novel metabolic pathways of organochlorine pesticides dieldrin and aldrin by the
      white rot fungi of the genus Phlebia.
AB  - White rot fungi can degrade a wide spectrum of recalcitrant organic pollutants,
      including polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated biphenyls
      (PCBs). In this experiment, 20 white rot fungi, belonging to genus Phlebia, were
      investigated for their ability to degrade dieldrin. Based on the screening
      results, we further investigated Phlebia acanthocystis, Phlebia brevispora, and
      Phlebia aurea to determine their degradation capacity and metabolic products
      towards dieldrin and aldrin. The three fungi were able to remove over 50% of
      dieldrin in a low nitrogen medium, after 42 d of incubation. Three hydroxylated
      products were detected as metabolites of dieldrin, suggesting that in Phlebia
      strains, hydroxylation reactions might play an important role in the metabolism
      of dieldrin. In contrast to dieldrin, aldrin exhibited higher levels of
      degradation activity. Over 90% of aldrin was removed after 28 d of incubation,
      and several new metabolites of aldrin in microorganisms, including 9
      hydroxyaldrin and two carboxylic acid products, were detected in fungal cultures.
      These results indicate that the methylene moiety of aldrin and dieldrin molecules
      might be prone to enzymatic attack by white rot fungi. In this study, we describe
      for the first time a new metabolic pathway of both compounds by fungi of genus
      Phlebia.

PMID- 21724226
TI  - Transcriptional profiles induced by the Aryl Hydrocarbon Receptor agonists
      2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran and
      2,3,4,7,8-pentachlorodibenzofuran in primary rat hepatocytes.
AB  - Toxicogenomics was used to examine mRNA expression profiles obtained from primary
      rat hepatocytes treated for 24h with 0.01 or 1.0 nM 2,3,7,8-tetrachlorodibenzo-p
      dioxin (2,3,7,8-TCDD), 0.02 or 2.0 nM 2,3,4,7,8-pentachlorodibenzofuran
      (2,3,4,7,8-PeCDF) and 0.1 or 10nM 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF).
      The concentrations of 2,3,4,7,8-PeCDF and 2,3,7,8-TCDF were chosen to be
      equivalent to 2,3,7,8-TCDD's concentration based on the toxic equivalency
      factor/toxic equivalent (TEF/TEQ) method for estimating biological potency.
      2,3,7,8-TCDD at 1.0 nM altered the expression of 533 genes; 2,3,4,7,8-PeCDF at
      2.0 nM altered 182 genes, and 2,3,7,8-TCDF at 10nM altered 154 genes. Of these,
      57 genes were affected by all three congeners. Agglomerative hierarchical
      clustering revealed distinct congener-dependent gene subclusters. Principal
      components analyses of the microarray data revealed that these congeners cluster
      independently of one another. Data presented here demonstrate that equivalent TEQ
      concentrations of 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF and 2,3,7,8-TCDF, while altering
      the expression of a small battery of genes in common, also produce substantial
      congener specific alterations in gene expression.

PMID- 21724227
TI  - Atmospheric bulk deposition of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) in the vicinity of an iron and steel making plant.
AB  - An IRA-743 resin bulk sampler was validated to monitor long-term bulk deposition
      of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Six consecutive
      sampling campaigns (2008-2009) were conducted at four sites around steel
      complexes in Pohang, South Korea to investigate spatial and seasonal variations
      of PCDD/F bulk deposition. The bulk deposition within the steel complex showed
      the highest ?(4-8)PCDD/F (Tetra-Octa) fluxes, ranging from 204 to 608 (mean:
      352)pg m(-2)d(-1), indicating steel complexes were major sources of PCDD/Fs. The
      homologue profiles were dominated with lower chlorinated PCDFs. Furthermore, the
      prevailing winds were confirmed to influence the spatial distribution of PCDD/F
      deposition. There were apparent seasonal variations of the bulk deposition at
      each site, and seasonal homologue patterns of PCDD/Fs were clearly observed.
      According to the passive air sampling, however, no significant seasonal change of
      ambient air concentrations of PCDD/Fs was observed. Therefore, it was concluded
      that the seasonal variations of deposition fluxes of PCDD/Fs probably resulted
      from temperature-dependent gas/particle partitioning.

PMID- 21724228
TI  - Plant uptake and in-soil degradation of PCB-5 under varying cropping conditions.
AB  - A 60-d greenhouse experiment was conducted to investigate the uptake and in-soil
      degradation of PCB-5 under single cropping and intercropping conditions involving
      three crop plant species: pumpkin, soybean and corn. Volatilization of PCB-5 from
      the soil surface was also tested. The results show that while uptake of PCB-5 by
      the test plant species is possible and the root concentration of PCB-5 had a
      control on the upward transport of PCB-5 to the above-ground portion of the
      plants, the PCB-5 extracted by the plants mainly accumulated in the root
      materials. Phytoextraction contributed insignificantly toward the loss of the
      soil-borne PCB-5. Volatilization of PCB-5 from the soil was recorded but it
      appeared that this did not result in a marked loss of PCB-5 in the bulk soil
      though it might cause remarkable removal of PCB-5 in a thin layer of the topsoil
      (1 mm). It is likely that the in-soil biodegradation contributed markedly to the
      observed reduction in soil-borne PCB-5. The in-soil biodegradation of PCB-5 was
      significantly enhanced under intercropping conditions, which appeared to be
      related to increased microbial activities, particularly bacterial activities. The
      soil residual PCB-5 was correlated with the activity of the following enzymes:
      catalase (CAT), polyphenol oxidase (PPO) and peroxidase (POD).

PMID- 21724229
TI  - Analysis of brominated flame retardants in house dust.
AB  - The main objective of this study was to create a robust analytical method to
      analyse the flame retardants decabromodiphenylether (BDE-209),
      hexabromocyclododecane (HBCD), and tetrabromobisphenol-A (TBBPA) in house dust in
      order to estimate the degree of contamination of indoor environment. A liquid
      chromatography method equipped with a UV-detector and electro spray-tandem mass
      spectrometry was used to achieve this result. Applying an external calibration
      for BDE-209, an internal calibration for TBBPA, and a standard addition method
      for HBCD low limits of quantification were obtained. The analytical procedure was
      carried out under exclusion of UV-light as the target compounds potentially
      degrade when being exposed to UV-light. Empirical data were obtained in addition
      to the dust samples to estimate potential influences of apartment
      characteristics. A weak correlation between the number of electric devices and
      TBBPA was found.

PMID- 21724230
TI  - Polychlorinated biphenyls (PCBs) in indoor air and in serum among older residents
      of upper Hudson River communities.
AB  - A study was conducted to evaluate the association between PCBs in residential
      indoor air and in the serum of older, long time residents of three upper Hudson
      River communities. Samples of indoor air and of serum were collected from 170
      persons 55 to 74 years of age, and analyzed for PCBs using glass capillary gas
      chromatography. After adjusting for age, BMI, cigarette smoking, and Hudson River
      fish consumption with multiple linear regression analysis, the results indicated
      statistically significant associations between concentrations in indoor air and
      serum for PCB-28, a lightly chlorinated congener common in air that accumulates
      in serum, and PCB-105. Duration of exposure was an important factor, since among
      persons who had lived in their home for 39 years or more, 11 of the 12 most
      commonly detected congeners were significantly correlated, as was their sum (?
      PCB). Significant associations between indoor air and serum PCB concentrations
      also were more likely when collected in cooler months and if the two samples were
      collected within 20 d of each other. The study is among the first to indicate
      that PCB concentrations characteristic of residential indoor air are associated
      with a detectable increase in body burden.

PMID- 21724231
TI  - Perfluorinated compounds in human blood around Bohai Sea, China.
AB  - Perfluorinated compounds (PFCs) including perfluorooctanoate (PFOA) and
      perfluorooctane sulfonate (PFOS) have been used in a wide range of industrial and
      consumer applications since 1960s. The previous studies have reported the
      occurrences of PFOS and PFOA in human blood and serum from various countries. In
      this study, 141 human whole blood samples collected from four cities around Bohai
      Sea in China including Qinhuangdao, Tangshan, Weihai, and Zouping were analyzed
      for PFCs. The highest median concentration of total PFCs was found in whole blood
      samples from Tangshan (14.01 ng mL(-1)). The median concentration of total PFCs
      in samples from Zouping (7.28 ng mL(-1)) was the lowest, but the median
      concentration of PFOA (3.26 ng mL(-1)) was the highest among four cities and the
      percentage proportion of PFOA (45%) was higher than that of PFOS (30%). Based on
      the different profiles of PFCs between coastal cities, it was suggested that
      there might be different human exposure sources and pathways of PFCs around Bohai
      Sea.

PMID- 21724232
TI  - Seasonal variation in the levels of organohalogen compounds in herring (Clupea
      harengus) from the Norwegian Sea.
AB  - The Norwegian spring spawning (NSS) herring is an ecologically important fish
      stock in the Norwegian Sea, and with a catch volume exceeding one million tons a
      year it is also economically important and a valuable food source. In order to
      provide a baseline of the levels of contaminants in this fish stock, the levels
      of organohalogen compounds were determined in 800 individual herring sampled at
      29 positions in the Norwegian Sea and off the coast of Norway. Due to seasonal
      migration, the herring were sampled where they were located during the different
      seasons. Concentrations of dioxins and dioxin-like PCBs, non-dioxin-like PCBs
      (PCB(7)) and PBDEs were determined in fillet samples of individual herring, and
      found to be relatively low, with means (min-max) of 0.77 (0.24-3.5) ng TEQ kg(-1)
      wet weight (ww), 5.0 (1.4-24) MUg kg(-1) ww and 0.47 (0.091-3.1) MUg kg(-1) ww,
      respectively. The concentrations varied throughout the year due to the feeding-
      and spawning cycle: Starved, pre-spawning herring caught off the Norwegian coast
      in January-February had the highest levels and those caught in the Norwegian Sea
      in April-June, after further starvation and spawning, had the lowest levels.
      These results show that the concentrations of organohalogen compounds in NSS
      herring are relatively low and closely tied to their physiological condition, and
      that in the future regular monitoring of NSS herring should be made in the
      spawning areas off the Norwegian coast in late winter.

PMID- 21724233
TI  - Diversity and community structure of culturable arsenic-resistant bacteria across
      a soil arsenic gradient at an abandoned tungsten-tin mining area.
AB  - We studied the bacterial diversity at a single location (the Terrubias mine;
      Salamanca province, Spain) with a gradient of soil As contamination to test if
      increasing levels of As would (1) change the preponderant groups of arsenic
      resistant bacteria and (2) increase the tolerance thresholds to arsenite
      [As(III)] and arsenate [As(V)] of such bacteria. We studied the genetic and
      taxonomic diversity of culturable arsenic-resistant bacteria by PCR
      fingerprinting techniques and 16S rRNA gene sequencing. Then, the tolerance
      thresholds to As(III) and As(V) were determined for representative strains and
      mathematically analyzed to determine relationships between tolerances to As(III)
      and As(V), as well as these tolerances with the soil contamination level. The
      diversity of the bacterial community was, as expected, inversely related to the
      soil As content. The overall preponderant arsenic-resistant bacteria were
      Firmicutes (mainly Bacillus spp.) followed by gamma-Proteobacteria (mainly
      Pseudomonas spp.), with increasing relative frequencies of the former as the soil
      arsenic concentration increased. Moreover, a strain of the species Rahnella
      aquatilis (gamma-Proteobacteria class) exhibited strong endurance to arsenic,
      being described for the first time in literature such a phenotype within this
      bacterial species. Tolerances of the isolates to As(III) and As(V) were
      correlated but not with their origin (soil contamination level). Most of the
      strains (64%) showed relatively low tolerances to As(III) and As(V), but the
      second most numerous group of isolates (19%) showed increased tolerance to
      As(III) rather than to As(V), even though the As(V) anion is the prevalent
      arsenic species in soil solution at this location. To our knowledge, this is the
      first study to report a shift towards preponderance of Gram-positive bacteria
      (Firmicutes) related to high concentrations of soil arsenic. It was also shown
      that, under aerobic conditions, strains with relatively enhanced tolerance to
      As(III) predominated over the most As(V)-tolerant ones.

PMID- 21724234
TI  - Quantification of the inhibitory effect of methyl fluoride on methanogenesis in
      mesophilic anaerobic granular systems.
AB  - The inhibitory effect of CH(3)F on methanogenesis in mesophilic anaerobic
      granules was tested at different concentrations (0-10% v/v, in the gas phase) and
      verified by the stable carbon isotopic signatures of CH(4) and CO(2). The results
      showed that the inhibitory effect increased with the initial CH(3)F concentration
      up to 5%. The CH(3)F concentration causing 50% metabolic inhibition was 0.32%.
      Complete inhibition of acetoclastic methanogenesis with a 91% reduction in total
      methanogenic activity was achieved when 5% CH(3)F was initially added to the
      headspace, which resulted in 870 MUM dissolved CH(3)F in the liquid. It was much
      higher than that applied in other natural anoxic non-granular systems, indicating
      that the layered granular structure influenced the inhibitory effect. The obvious
      increase in hydrogen content indicated that high concentrations of CH(3)F (>=5%)
      suppressed hydrogenotrophic methanogenesis as well. The stable inhibition lasted
      for at least 6d as the CH(3)F concentration decreased slowly with incubation
      time. These results suggested that CH(3)F could be used for investigating
      methanogenic processes in anaerobic granular systems after the CH(3)F
      concentration and incubation time for specific inhibition of acetoclastic
      methanogenesis were carefully determined. In the present system, CH(3)F
      concentration of 5% was suggested to be optimal.

PMID- 21724235
TI  - Persistent organic pollutants associated to water fluxes and sedimentary
      processes in the Colorado River delta, Baja California, Mexico.
AB  - Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were
      studied in sediment cores from two distinctive modern channels of the Colorado
      River (CR) delta. Their abundance and temporal changes are associated with flood
      flows from the CR across the USA-Mexico border. The CR channel is directly
      exposed to river flood-flows while the Hardy River (HR) is a local channel
      derived mainly from agricultural runoff, geothermal effluents, and treated urban
      wastewater. Different headwater compositions and degrees of exposure to flood
      flows appear to be the factors controlling the composition of persistent organic
      pollutants (POPs). Enrichment of OCPs (46 ng g(-1) dwt in HR and 4.37 ng g(-1)
      dwt in CR) occurred during or a few years after flooding. PCB-138 (4.2 ng g(
      1)dwt) is enriched in HR suggesting its origin in dielectric oils from the
      geothermal power plant. PCB-28 (2.1 ng g(-1)dwt) in CR may be related with
      atmospheric input and/or re-deposition of upstream sediments. In surficial
      sediments (0-3 cm), only HR exceeds international sediment quality guidelines
      (4,4'-DDE=8.16 ng g(-1)dwt and SigmaDDT=8.34 ng g(-1)dwt).

PMID- 21724236
TI  - Chemosphere phosphorus cycle issue--introduction.

PMID- 21724237
TI  - The effect of man made source processes on the behavior of total gaseous mercury
      in air: a comparison between four urban monitoring sites in Seoul Korea.
AB  - Concentrations of total gaseous mercury (TGM) were measured continuously at four
      urban residential locations (G (Guro-gu); N (Nowon-gu); S (Songpa-gu); and Y
      (Yongsan-gu)) in Seoul, Korea from 2004 to 2009. The mean concentrations of Hg at
      these sites were found on the order of N (3.98+/-1.68 ng m(-3)), S (3.87+/-1.56
      ng m(-3)), G (3.80+/-1.60 ng m(-3)), and Y (3.36+/-1.55 ng m(-3)). Evidence
      indicates that the spatial distribution of Hg should be affected by the combined
      effects of both local anthropogenic (incineration facilities and thermal power
      plants) and natural (soil) emission sources in association with the
      meteorological parameters. Inspection of the Hg temporal patterns indicates the
      co-existence of contrasting seasonal patterns between the central site Y (winter
      dominance) and all other outbound sites near city borders (summer dominance). The
      long-term trend of Hg, if examined by combining our previous studies and the
      present one, shows that Hg levels in this urban area declined gradually across
      decadal periods despite slight variabilities in spatial scale: (1) above 10 ng m(
      3) in the late 1980s, (2) ~5 ng m(-3) in the late 1990s, and (3) ~3 ng m(-3)
      toward the late 2000s. The results of the principal component analysis along with
      observed differences in seasonal patterns (between study sites) suggest that Hg
      distributions between different urban sites are greatly distinguishable with
      strong source signatures at each individual site.

PMID- 21724238
TI  - PM10 composition during an intense Saharan dust transport event over Athens
      (Greece).
AB  - The influence of Saharan dust on the air quality of Southern European big cities
      became a priority during the last decade. The present study reports results on
      PM(10) monitored at an urban site at 14 m above ground level during an intense
      Saharan dust transport event. The elemental composition was determined by Energy
      Dispersive X-ray Fluorescence Spectrometry (EDXRF) for 12 elements: Si, Al, Fe,
      K, Ca, Mg, Ti, S, Ni, Cu, Zn and Mn. PM(10) concentrations exceeded the EU limit
      (50 MUg/m(3)) several times during the sampling period. Simultaneous maxima have
      been observed for the elements of crustal origin. The concentrations of all the
      elements presented a common maximum, corresponding to the date where the
      atmosphere was heavily charged with particulate matter permanently for an
      interval of about 10h. Sulfur and heavy metal concentrations were also associated
      to local emissions. Mineral dust represented the largest fraction of PM(10)
      reaching 79%. Seven days back trajectories have shown that the air masses
      arriving over Athens, originated from Western Sahara. Scanning Electron
      Microscopy coupled with Energy Dispersive X-ray analysis (SEM-EDX) revealed that
      particle agglomerates were abundant, most of them having sizes <2 MUm.
      Aluminosilicates were predominant in dust particles also rich in calcium which
      was distributed between calcite, dolomite, gypsum and Ca-Si particles. These
      results were consistent with the origin of the dust particles and the elemental
      composition results. Sulfur and heavy metals were associated to very fine
      particles <1 MUm.

PMID- 21724239
TI  - Human biokinetic data and a new compartmental model of zirconium--a tracer study
      with enriched stable isotopes.
AB  - Biokinetic models describing the uptake, distribution and excretion of trace
      elements are an essential tool in nutrition, toxicology, or internal dosimetry of
      radionuclides. Zirconium, especially its radioisotope (95)Zr, is relevant to
      radiation protection due to its production in uranium fission and neutron
      activation of nuclear fuel cladding material. We present a comprehensive set of
      human data from a tracer study with stable isotopes of zirconium. The data are
      used to refine a biokinetic model of zirconium. Six female and seven male healthy
      adult volunteers participated in the study. It includes 16 complete double tracer
      investigations with oral ingestion and intravenous injection, and seven
      supplemental investigations. Tracer concentrations were measured in blood plasma
      and urine collected up to 100 d after tracer administration. The four data sets
      (two chemical tracer forms in plasma and urine) each encompass 105-240 measured
      concentration values above detection limits. Total fractional absorption of
      ingested zirconium was found to be 0.001 for zirconium in citrate-buffered
      drinking solution and 0.007 for zirconium oxalate solution. Biokinetic models
      were developed based on the linear first-order kinetic compartmental model
      approach used by the International Commission on Radiological Protection (ICRP).
      The main differences of the optimized systemic model of zirconium to the current
      ICRP model are (1) recycling into the transfer compartment made necessary by the
      observed tracer clearance from plasma, (2) different parameters related to
      fractional absorption for each form of the ingested tracer, and (3) a
      physiologically based excretion pathway to urine. The study considerably expands
      the knowledge on the biokinetics of zirconium, which was until now dominated by
      data from animal studies. The proposed systemic model improves the existing ICRP
      model, yet is based on the same principles and fits well into the ICRP radiation
      protection approach.

PMID- 21724240
TI  - Concentration and size distribution of bioaerosols in an outdoor environment in
      the Qingdao coastal region.
AB  - Bioaerosol particles in the atmosphere were collected from the coastal region of
      Qingdao from Jul. 2009 to Jun. 2010. The concentrations of microorganisms
      (including culturable, nonculturable, terrestrial and marine microorganisms) were
      measured. Average concentrations of airborne terrestrial bacteria, marine
      bacteria, terrestrial fungi, marine fungi and total bioaerosol were in the ranges
      of 33-664 CFU/m(3), 63-815 CFU/m(3), 2-777 CFU/m(3), 66-1128 CFU/m(3) and 85,015
      166,094 Cells/m(3), respectively. The nonculturable microbes accounted for 99.13%
      of the total microbes. In addition, there were more culturable marine microbes
      than culturable terrestrial microbes, and more airborne fungi than bacteria. The
      concentration of airborne bacteria showed a skewed distribution pattern, while
      unimodal size distributions were observed for the concentrations of fungi and
      total microbes. The airborne microbes mainly existed in >2.1 MUm coarse
      particles. Pearson correlation analysis between the concentrations and
      meteorological parameters showed that the meteorological parameters had different
      effects on different kinds of microbes. Sandstorms increased the concentrations
      of both culturable microbes and total microbes in the bioaerosol.

PMID- 21724241
TI  - How to calculate the spatial distribution of ecosystem services--natural
      attenuation as example from The Netherlands.
AB  - Maps play an important role during the entire process of spatial planning and
      bring ecosystem services to the attention of stakeholders' negotiation more
      easily. As example we show the quantification of the ecosystem service 'natural
      attenuation of pollutants', which is a service necessary to keep the soil clean
      for production of safe food and provision of drinking water, and to provide a
      healthy habitat for soil organisms to support other ecosystem services. A method
      was developed to plot the relative measure of the natural attenuation capacity of
      the soil in a map. Several properties of Dutch soils were related to property
      specific reference values and subsequently combined into one proxy for the
      natural attenuation of pollutants. This method can also be used to map other
      ecosystem services and to ultimately integrate suites of ecosystem services in
      one map.

PMID- 21724242
TI  - Renal cell carcinoma with inferior vena cava tumor thrombus and metastatic caval
      wall invasion.
AB  - We present a case of renal cell carcinoma with inferior vena caval tumor thrombus
      and metastatic involvement of the distal inferior vena cava.

PMID- 21724243
TI  - Critical role of IL-21 in modulating TH17 and regulatory T cells in Behcet
      disease.
AB  - BACKGROUND: Behcet disease (BD) is a chronic systemic inflammatory disorder of
      unknown etiology. OBJECTIVE: To determine the nature of T cells driving
      inflammatory lesions in BD. METHODS: T cell homeostasis and cytokines production
      were analyzed in peripheral blood and brain inflammatory lesions from 45 adult
      patients with BD (active and untreated BD [n = 25] and patients in remission [n =
      20]) and 20 healthy donors, using Luminex, flow cytometry, immunohistochemistry,
      and immunofluorescence analysis. RESULTS: We found a marked increase in T(H)17
      cells and a decrease in the frequency of CD4(+) forkhead box P3(+) regulatory T
      cells (Tregs) in peripheral blood that were induced by IL-21 production and that
      correlate with BD activity. The addition of serum from patients with active BD in
      a sorted CD4(+) T cells culture of healthy donors induced a significant and dose
      dependent production of IL-17A and a decrease in forkhead box P3 expression. We
      demonstrated the presence of IL-21- and IL-17A-producing T cells within the
      cerebrospinal fluid, brain parenchyma inflammatory infiltrates, and intracerebral
      blood vessels from patients with active BD and central nervous system
      involvement. The stimulation of CD4(+) T cells with IL-21 increased T(H)17 and
      T(H)1 differentiation and decreased the frequency of Treg cells. Conversely, IL
      21 blockade with an IL-21R-Fc restored the T(H)17 and Treg homeostasis in
      patients with BD. CONCLUSION: We provided here the first evidence of the critical
      role of IL-21 in driving inflammatory lesions in BD by promoting T(H)17 effectors
      and suppressing Treg cells. IL-21 represents a promising target for novel therapy
      in BD.

PMID- 21724245
TI  - Expanding the reach of breakthroughs.

PMID- 21724244
TI  - The "Perceptual Wedge Hypothesis" as the basis for bilingual babies' phonetic
      processing advantage: new insights from fNIRS brain imaging.
AB  - In a neuroimaging study focusing on young bilinguals, we explored the brains of
      bilingual and monolingual babies across two age groups (younger 4-6 months, older
      10-12 months), using fNIRS in a new event-related design, as babies processed
      linguistic phonetic (Native English, Non-Native Hindi) and non-linguistic Tone
      stimuli. We found that phonetic processing in bilingual and monolingual babies is
      accomplished with the same language-specific brain areas classically observed in
      adults, including the left superior temporal gyrus (associated with phonetic
      processing) and the left inferior frontal cortex (associated with the search and
      retrieval of information about meanings, and syntactic and phonological
      patterning), with intriguing developmental timing differences: left superior
      temporal gyrus activation was observed early and remained stably active over
      time, while left inferior frontal cortex showed greater increase in neural
      activation in older babies notably at the precise age when babies' enter the
      universal first-word milestone, thus revealing a first-time focal brain correlate
      that may mediate a universal behavioral milestone in early human language
      acquisition. A difference was observed in the older bilingual babies' resilient
      neural and behavioral sensitivity to Non-Native phonetic contrasts at a time when
      monolingual babies can no longer make such discriminations. We advance the
      "Perceptual Wedge Hypothesis" as one possible explanation for how exposure to
      greater than one language may alter neural and language processing in ways that
      we suggest are advantageous to language users. The brains of bilinguals and
      multilinguals may provide the most powerful window into the full neural "extent
      and variability" that our human species' language processing brain areas could
      potentially achieve.

PMID- 21724247
TI  - The influence of PEG chain length and targeting moiety on antibody-mediated
      delivery of nanoparticle vaccines to human dendritic cells.
AB  - Targeted delivery of nanoparticles (NPs) carrying vaccine components to dendritic
      cells (DCs) is a promising strategy to initiate antigen-specific immune
      responses. Improving the interactions between nanoparticle-carried ligands and
      receptors on DCs is a major challenge. These NPs are generally coated with
      poly(ethylene glycol) (PEG), to shield non-specific interactions, and antibodies,
      to facilitate specific delivery to DC surface receptors. We have devised a
      strategy to covalently link PEG molecules of various chain length (Mw 2000-20000
      g/moL) to poly(lactic-co-)glycolic acid (PLGA) NP vaccines. We coated these NPs
      with various antibodies recognizing the DC-specific receptor DC-SIGN to study the
      effects of shielding and antibody type on antibody--receptor interactions.
      Chemical attachment of PEG to the particle surface was followed by detailed zeta
      potential, DLS and NMR studies, and analyzed by analytical chemistry. Increasing
      the PEG chain length increased particle size and polydispersity index and reduced
      the intracellular degradation rate of encapsulated antigens. Binding and uptake
      of NPs by human DCs was affected by both PEG chain length and antibody type. NPs
      coated with PEG-3000 had the optimal chain length for antibody--receptor
      interactions and induction of antigen-specific T-cell responses. Interestingly,
      clear differences were observed upon targeting distinct epitopes of the same
      receptor. Binding and uptake of NPs carrying antibodies recognizing the
      carbohydrate recognition domain of DC-SIGN was enhanced when compared to those
      carrying antibodies recognizing the receptor's neck region. In conclusion, our
      data show that PEG chains cannot be extended beyond a certain length for
      shielding purposes without compromising the efficacy of targeted delivery.
      Thereby, the implications of our findings are not limited to the future design of
      nanovaccines specifically targeted to DC-SIGN, but apply to the general design of
      targeted nanocarriers.

PMID- 21724248
TI  - A highly organized three-dimensional alginate scaffold for cartilage tissue
      engineering prepared by microfluidic technology.
AB  - Osteoarthritis is a degenerative disease and frequently involves the knee, hip
      and phalangeal joints. Current treatments used in small cartilage defects
      including multiple drilling, abrasion arthroplasty, mosaicplasty, and autogenous
      chondrocyte transplantation, however, there are problems needed to be solved. The
      standard treatment for severe osteoarthritis is total joint arthroplasty. The
      disadvantages of this surgery are the possibility of implant loosening.
      Therefore, tissue engineering for cartilage regeneration has become a promising
      topic. We have developed a new method to produce a highly organized single
      polymer (alginate) scaffold using microfluidic device. Scanning electron
      microscope and confocal fluoroscope examinations showed that the scaffold has a
      regular interconnected porous structure in the scale of 250 MUm and high
      porosity. The scaffold is effective in chondrocyte culture; the cell viability
      test (WST-1 assay), cell toxicity (lactate dehydrogenase assay), cell survival
      rate, extracellular matrix production (glycosaminoglycans contents), cell
      proliferation (DNA quantification), and gene expression (real-time PCR) all
      revealed good results for chondrocyte culture. The chondrocytes can maintain
      normal phenotypes, highly express aggrecan and type II collagen, and secrete a
      great deal of extracellular matrix when seeded in the alginate scaffold. This
      study demonstrated that a highly organized alginate scaffold can be prepared with
      an economical microfluidic device, and this scaffold is effective in cartilage
      tissue engineering.

PMID- 21724249
TI  - A review of NIR dyes in cancer targeting and imaging.
AB  - The development of multifunctional agents for simultaneous tumor targeting and
      near infrared (NIR) fluorescence imaging is expected to have significant impact
      on future personalized oncology owing to the very low tissue autofluorescence and
      high tissue penetration depth in the NIR spectrum window. Cancer NIR molecular
      imaging relies greatly on the development of stable, highly specific and
      sensitive molecular probes. Organic dyes have shown promising clinical
      implications as non-targeting agents for optical imaging in which indocyanine
      green has long been implemented in clinical use. Recently, significant progress
      has been made on the development of unique NIR dyes with tumor targeting
      properties. Current ongoing design strategies have overcome some of the
      limitations of conventional NIR organic dyes, such as poor hydrophilicity and
      photostability, low quantum yield, insufficient stability in biological system,
      low detection sensitivity, etc. This potential is further realized with the use
      of these NIR dyes or NIR dye-encapsulated nanoparticles by conjugation with tumor
      specific ligands (such as small molecules, peptides, proteins and antibodies) for
      tumor targeted imaging. Very recently, natively multifunctional NIR dyes that can
      preferentially accumulate in tumor cells without the need of chemical conjugation
      to tumor targeting ligands have been developed and these dyes have shown unique
      optical and pharmaceutical properties for biomedical imaging with superior signal
      to-background contrast index. The main focus of this article is to provide a
      concise overview of newly developed NIR dyes and their potential applications in
      cancer targeting and imaging. The development of future multifunctional agents by
      combining targeting, imaging and even therapeutic routes will also be discussed.
      We believe these newly developed multifunctional NIR dyes will broaden current
      concept of tumor targeted imaging and hold promise to make an important
      contribution to the diagnosis and therapeutics for the treatment of cancer.

PMID- 21724250
TI  - Microenvironment induced spheroid to sheeting transition of immortalized human
      keratinocytes (HaCaT) cultured in microbubbles formed in polydimethylsiloxane.
AB  - The in vivo cellular microenvironment is regulated by a complex interplay of
      soluble factors and signaling molecules secreted by cells and it plays a critical
      role in the growth and development of normal and diseased tissues. In vitro
      systems that can recapitulate the microenvironment at the cellular level are
      needed to investigate the influence of autocrine signaling and extracellular
      matrix effects on tissue homeostasis, regeneration, disease development and
      progression. In this study, we report the use of microbubble technology as a
      means to culture cells in a controlled microenvironment in which cells can
      influence their function through autocrine signaling. Microbubbles (MB) are small
      spherical cavities about 100-300 MUm in diameter formed in hydrophobic
      polydimethylsiloxane (PDMS) with ~60-100 MUm circular openings and aspect ratio
      ~3.0. We demonstrate that the unique architecture of the microbubble compartment
      is advantaged for cell culture using HaCaT cells, an immortalized keratinocyte
      cell line. We observe that HaCaT cells, seeded in microbubbles (15-20 cells/MB)
      and cultured under standard conditions, adopt a compact 3D spheroidal morphology.
      Within 2-3 days, the cells transition to a sheeting morphology. Through
      experimentation and simulation we show that this transition in morphology is due
      to the unique architecture of the microbubble compartment which enables cells to
      condition their local microenvironment. The small media volume per cell and the
      development of shallow concentration gradients allow factors secreted by the
      cells to rise to bioactive levels. The kinetics of the morphology transition
      depends on the number of cells seeded per microbubble; higher cell seeding
      induces a more rapid transition. HaCaT cells seeded onto PDMS cured in 96-well
      plates also form compact spheroids but they do not undergo a transition to a
      sheeting morphology even after several weeks of culture. The importance of
      soluble factor accumulation in driving this morphology transition in microbubbles
      is supported by the observation that spheroids do not form when cells - seeded
      into microbubbles or onto PDMS cured in 96-well plates - are cultured in media
      conditioned by HaCaT cells grown in standard tissue culture plate. We observed
      that the addition of TGF-beta1 to the growth media induced cells to proliferate
      in a sheeting morphology from the onset both on PDMS cured in 96-well plates and
      in microbubbles. TGF-beta1 is a morphogen known to regulate epithelial-to
      mesenchymal transition (EMT). Studies of the role of Ca(2+) concentration and
      changes in E-cadherin expression additionally support an EMT-like HaCaT
      morphology transition. These findings taken together validate the microbubble
      compartment as a unique cell culture platform that can potentially transform
      investigative studies in cell biology and in particular the tumor
      microenvironment. Targeting the tumor microenvironment is an emerging area of
      anti-cancer therapy.

PMID- 21724251
TI  - The effect of stromal components on the modulation of the phenotype of human
      bronchial epithelial cells in 3D culture.
AB  - The stroma plays an important role in the development and progression of human
      diseases. Pulmonary diseases such as asthma, fibrosis and cancer are thought to
      be the result of altered communications between the epithelial and stromal tissue
      compartments. In order to study these epithelial-mesenchymal interactions, we
      developed a three dimensional (3D) in vitro model of the human airway that mimics
      bronchial morphology and function. This model consists of a type-I collagen
      matrix, normal human fetal lung fibroblasts (IMR-90) or primary human adult lung
      cancer-associated fibroblasts (LuCAFs), and a surface epithelium of normal human
      bronchial epithelial cells (HBECs). When cultured at an air-liquid interface
      (ALI), the epithelial component generated a well-differentiated pseudo-stratified
      bronchial epithelium that contained basal, ciliated, and non-ciliated (secretory)
      epithelial cells. IMR-90 and LuCAFs differentially altered the phenotype of HBECs
      in distinct ways. While IMR-90 permitted HBECs to form a typical respiratory
      surface epithelium, LuCAFs promoted HBECs to invade the collagen gel forming both
      epithelial nodules and cysts, suggesting that LuCAFs may alter the HBEC phenotype
      by modifying biomechanical signals conveyed through the extracellular matrix
      (ECM). Furthermore, LuCAFs secreted soluble factors that induced HBECs to express
      genes associated with immune responses, apoptosis, mitosis, cell survival,
      differentiation and cancer.

PMID- 21724252
TI  - The effect of decellularized bone/bone marrow produced by high-hydrostatic
      pressurization on the osteogenic differentiation of mesenchymal stem cells.
AB  - Decellularized bone/bone marrow was prepared to provide a microenvironment
      mimicking that of the bone marrow for three-dimensional culture in vitro.
      Bone/bone marrows were hydrostatically pressed at 980 MPa at 30  degrees C for 10
      min to dismantle the cells. Then, they were washed with EGM-2 and further treated
      in an 80% EtOH to remove the cell debris and lipid, respectively. After being
      rinsed and shaken with PBS again, treated bone/bone marrows were stained with
      hematoxylin and eosin (H-E) to assess the efficacy of decellularization. Cells
      were determined to have been completely removed through H-E staining of their
      sections and DNA quantification. Rat mesenchymal stem cells (rMSCs) were seeded
      on the decellularized bone/bone marrows and cultured for 21 days. The adhesion of
      rMSCs on or into decellularized bone/bone marrows was confirmed and proliferated
      over time in culture. The osteogenic differentiation effect of decellularized
      bone/bone marrows on rMSCs in the presence or absence of dexamethasone was
      investigated. Decellularized bone/bone marrows without dexamethasone
      significantly increased alkaline phosphatase (ALP) activity, indicating promoted
      osteogenic differentiation of rMSCs. In an animal study, when decellularized
      bone/bone marrows were implanted into the rat subcutaneous, no immune reaction
      occurred and clusters of the hematopoietic cells could be observed, suggesting
      the decellularized bone/bone marrows can provide a microenvironment in vivo.

PMID- 21724253
TI  - Cellular uptake, cytotoxicity, and ROS generation with silica/conducting polymer
      core/shell nanospheres.
AB  - The cellular response to conducting polymer (CP) nanospheres with similar
      physical properties was evaluated by in vitro cellular uptake and cytotoxicity in
      mouse macrophage RAW 264.7 and rat pheochromocytoma PC-12 cells. Four different
      CPs (polythiophene, poly(3,4-ethylenedioxythiophene), polyaniline, and
      polypyrrole) were deposited onto silica nanoparticles with a diameter of ca. 22
      nm. Cellular uptake of silica/CP core/shell nanospheres in both cell lines was
      observed by transmission electron microscopy and they were internalized via
      phagocytosis and endocytosis. Cytotoxic effects were systemically assessed using
      live-cell microscopy, viability, oxidative stress, and lactate dehydrogenase
      assays. Silica/polythiophene core/shell nanospheres were the most toxic in both
      cell lines examined, because of the cellular effects of sulfur atoms. On the
      other hand, silica/polypyrrole core/shell nanospheres caused the lowest levels of
      toxicity in both cell lines. Furthermore, both rat and mouse cell viability was
      concentration-dependent with the nanospheres. These findings enhance
      nanotoxicological information regarding CP nanospheres when used with macrophage
      and neuronal cells, which may be useful in their application in bioelectronic and
      biomedical fields.

PMID- 21724254
TI  - Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases.
AB  - Disrupted cellular Ca(2+) signaling is believed to play a role in a number of
      human diseases including lysosomal storage diseases (LSD). LSDs are a group of
      ~50 diseases caused predominantly by mutations in lysosomal proteins that result
      in accumulation of macromolecules within the lysosome. We recently reported that
      Niemann-Pick type C (NPC) is the first human disease to be associated with
      defective lysosomal Ca(2+) uptake and defective NAADP-mediated lysosomal Ca(2+)
      release. These defects in NPC cells leads to the disruption in endocytosis and
      subsequent lipid storage that is a feature of this disease. In contrast, Chediak
      Higashi Syndrome cells have been reported to have enhanced lysosomal Ca(2+)
      uptake whilst the TRPML1 protein defective in mucolipidosis type IV is believed
      to function as a Ca(2+) channel. In this review we provide a summary of the
      current knowledge on the role of lysosomal Ca(2+) signaling in the pathogenesis
      of this group of diseases.

PMID- 21724255
TI  - Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to
      imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia.
AB  - The function of the natural modulators of BCR-ABL-induced signaling pathways
      could influence the results to imatinib treatment. We assessed the association
      between single nucleotide polymorphisms (SNPs) on genes of the phosphatase family
      and the suppressors of cytokine signaling and the response to imatinib in 105
      patients newly diagnosed with chronic-phase CML. SNPs in SOCS1 (rs243327) and
      PTPN22 (rs2476601) genes correlated with the risk of primary resistance to
      imatinib. A high-risk Sokal score, the T allele in PTPN22 SNP, and each copy of
      the C allele in SOCS1 SNP were adverse prognostic factors for failure-free
      survival (FFS). Based on such parameters, three risk groups were identified, with
      the 5-year FFS for each group being 95%, 75%, and 50%, respectively (P<0.001). A
      simple predictive model including Sokal score and genotype of SOCS1 and PTPN22
      SNPs may be useful in the selection of the initial treatment in CML.

PMID- 21724256
TI  - MicroRNA-193b regulates c-Kit proto-oncogene and represses cell proliferation in
      acute myeloid leukemia.
AB  - Mutations and/or overexpression of c-Kit proto-oncogene frequently occur in
      subsets of acute myeloid leukemia (AML) and contribute to abnormal cell
      proliferation and poor outcomes. We showed that c-Kit expression was subject to
      post-transcriptional regulation by microRNA (miRNA)-193b. Notably, miR-193b was
      significantly down-regulated in the examined AML cells and its levels were
      inversely correlated with c-Kit levels. Restoration of miR-193b expression in AML
      cells resulted in distinctly reduced c-Kit expression and inhibited cell growth.
      These data reveal a role for miR-193b dysregulation in myeloid leukemogenesis and
      the therapeutic promise of regulating miR-193b expression for c-Kit-positive AML.

PMID- 21724257
TI  - Heavy metal induced physiological alterations in Salvinia natans.
AB  - Salvinia possess inherent capacity to accumulate high levels of various heavy
      metals. Accumulation of Cr, Fe, Ni, Cu, Pb and Cd ranged between 6 and 9 mg g(
      1)dry wt., while accumulation of Co, Zn and Mn was ~4 mg g(-1)dry wt. Heavy metal
      accumulation affected the physiological status of plants. Photosystem II activity
      noted to decline in Ni, Co, Cd, Pb, Zn and Cu exposed plants, while Photosystem I
      activity showed enhancement under heavy metal stress in comparison to control.
      The increase in PS I activity supported build up of transthylakoidal proton
      gradient (DeltapH), which subsequently helped in maintaining the
      photophosphorylation potential. Ribulose 1,5 dicarboxylase/oxygenase (Rubisco)
      activity noted a decline. Alterations in photosynthetic potential of Salvinia
      result primarily from changes in carbon assimilation efficiency with slight
      variations in primary photochemical activities and photophosphorylation
      potential. Studies suggest that Salvinia possess efficient photosynthetic
      machinery to withstand heavy metal stress.

PMID- 21724258
TI  - Evaluation of the joint effect of glyphosate and dimethoate using a small-scale
      terrestrial ecosystem.
AB  - In the present work a small-scale terrestrial ecosystem (STEM) containing a soil
      collected from an agricultural field in Central Portugal was used to evaluate the
      effects of the combination of the herbicide glyphosate and the insecticide
      dimethoate. Earthworms (Eisenia andrei), isopods (Porcellionides pruinosus),
      turnip seeds (Brassica rapa), and bait-lamina strips were placed in the STEM. The
      results showed that the application of the recommended field dose of both
      pesticides did not cause any effect on the weight variation of earthworms and
      growth of the plants. The application of the herbicide, even at 5 and 10 times
      the field dose, increased feeding activity in soil (bait-lamina test), although
      the application of dimethoate led to a decrease in feeding activity in all
      concentrations tested. The binary mixtures performed showed that according to the
      Independent Action model, synergism (higher effect than expected from the single
      exposures) was observed in both the shoot length and fresh weight of B. rapa at 5
      times the field dose, but antagonism was observed at 10 times the field dose.
      Regarding the germination success, synergism was observed at the field dose, but
      antagonism was detected at 5 times and 10 times the field dose. There was a
      decrease on the earthworm's weight in all concentrations tested, although no
      statistical differences were observed in any of the treatments made. Regarding
      depth distribution of E. andrei, worms were found in the upper layer more than it
      was predicted for all concentrations. In the mixtures with the field and 5 times
      the field dose there was a decrease in the feeding activity (bait-lamina
      consumption) by the soil fauna. From the four biomarkers assessed on the isopods
      (Catalase, Acetylcholinesterase, Glutathione-S-transferase, and Lipid
      peroxidation), only a significant decrease in the Acetylcholinesterase activity
      upon dimethoate and the binary mixtures exposures performed with the field dose
      was observed and on Lipid peroxidation at the field doses of single and binary
      exposures.

PMID- 21724259
TI  - Hirayama disease: an uncommon cause of distal upper extremity deficit.
AB  - Hirayama disease is a myelopathy related to flexion movements of the neck that
      produce ischemic damage in the anterior horn of the cervical cord. The disease
      affects young people and is characterized by a distal upper extremity deficit
      that develops gradually. The diagnosis is confirmed by cervical magnetic
      resonance imaging (MRI) in flexion demonstrating a forward shift of the posterior
      dural sac and spinal cord compression. On radiology, there should be suggestive
      signs in neutral position such as cord atrophy, intramedullary bilateral high
      signal intensity on T2-weighted images, straightening of the cervical spine, and
      loss of attachment between the posterior dural sac and subjacent lamina.
      Exploration should be completed by an MR study in neck flexion. We report here on
      two typical cases of the disease and also include a review of the literature.

PMID- 21724260
TI  - Tympanoplasty: an up-to-date pictorial review.
AB  - The indications for tympanoplasty are mainly chronic ear pathologies, such as
      cholesteatoma, atelectasis and chronic tympanosclerotic otitis. Usually,
      modification of the mastoid and temporal tissues in general mostly involves bone
      work, which means bone removal by burs or appropriate bone curettes. It is for
      this reason that, in both the pre- and postoperative periods, the computed
      tomography (CT) scan is the primary radiological tool for studying the middle
      ear, and temporal bone structures and pathologies. The aim of this review is to
      illustrate the most up-to-date postoperative results for tympanoplasty, including
      the emerging endoscopic techniques. The present work focuses on the five types of
      tympanoplasty that are likely to be encountered by the radiologist: radical
      surgery; open tympanoplasty; closed tympanoplasty; closed endoscopic
      tympanoplasty; and open endoscopic tympanoplasty. Understanding and interpreting
      temporal bone images in relation to the different types of surgery are important,
      especially at the postoperative stage, because of the high risk of recurrence of
      middle-ear pathologies, and a good working knowledge of surgical changes is
      fundamental for distinguishing iatrogenic bone demolition from complications and
      new pathological foci.

PMID- 21724261
TI  - Rapid cell division contributes to efficient induction of A/T mutations during Ig
      gene hypermutation.
AB  - Ig gene hypermutation is initiated by the activation-induced cytidine deaminase
      (AID), which converts cytosine to uracil and generates a U:G lesion. One of the
      unsolved mysteries is how AID-triggered U:G lesions result in efficient induction
      of mutations at non-damaged A/T bases in the V(H) genes of germinal center (GC) B
      cells. Genetic and biochemical evidence suggests that components of the mismatch
      repair pathway and the low fidelity DNA polymerase eta are required for the
      induction of A/T mutations. However, mismatch repair proficient NIH3T3 cells are
      unable to generate a high frequency of A/T mutations, even after DNA polymerase
      eta overexpression, suggesting that additional mechanisms are involved. Since GC
      B cells undergo enormous expansion while undergoing hypermutation, we
      hypothesized that rapid cell division might play a role in the induction of A/T
      mutations. To test this hypothesis, we utilized an efficient in vitro mutagenesis
      system, which closely mirrors physiological Ig gene hypermutation, in the human
      GC-like B cell line Ramos. Ramos cells transduced with AID-IRES-GFP retrovirus
      were cultured for 10 days in medium supplemented with 20% or 2% fetal bovine
      serum (FBS) to allow rapid and slow proliferation, respectively. Analysis of the
      V(H) gene mutations revealed that A/T mutations were significantly reduced in 2%
      FBS compared with 20% FBS, with transitions more affected than transversions.
      These results demonstrate that rapid cell division contributes to efficient
      induction of A/T mutations and suggest that the rate of DNA replication has a
      profound effect on the processing of AID-triggered U:G lesions.

PMID- 21724262
TI  - Monocular trial of intraocular pressure-lowering medication: a prospective study.
AB  - OBJECTIVE: To investigate the validity of the monocular therapeutic trial of
      therapy in patients commencing topical glaucoma treatment. DESIGN: Prospective
      intention-to-treat cohort study of untreated patients presenting with open-angle
      glaucoma or ocular hypertension. PARTICIPANTS: We included 30 treatment-naive
      subjects. INTERVENTION: All subjects had 8 visits at which intraocular pressure
      (IOP) was measured by masked Goldmann tonometry. After the recruitment visit, IOP
      was measured in both eyes at 11 am for 7 consecutive weeks. At week 3, travaprost
      (0.001%) was commenced in the eye with the higher IOP and at week 4 travaprost
      was also commenced in the fellow eye. MAIN OUTCOME MEASURES: Three IOP outcomes
      were measured for the trial eye: (1) Unadjusted IOP-lowering effect (difference
      between recruitment IOP and first IOP on treatment); (2) adjusted IOP-lowering
      effect (unadjusted effect - [difference between IOPs at the same visits in the
      fellow eye]); and (3) true therapeutic effect (mean difference between 3 baseline
      pretreatment IOPs and 3 IOPs on treatment). RESULTS: Mean recruitment IOPs were
      28.2 and 26.0 mmHg in the trial and fellow eyes, respectively. The mean baseline
      IOPs were 25.8 and 22.7 mmHg in the trial and fellow eyes, respectively,
      indicating that regression to the mean was responsible for 2.4 and 3.3 mmHg,
      respectively, in the trial and fellow eyes. The unadjusted treatment effect (11.7
      mmHg) overestimated the true effect (8.6 mmHg) by a mean of 3.1 mmHg, whereas the
      mean adjusted IOP was almost identical to the true effect. The correlation
      between the unadjusted effect of treatment and the true effect was 0.55, whereas
      the effect when adjusted by the monocular trial was 0.72. CONCLUSIONS: In our
      cohort of patients with bilateral IOPs >21 mmHg at baseline, the monocular trial
      provides a significantly more accurate estimate of the therapeutic response when
      initiating prostaglandin monotherapy in untreated eyes. It is particularly
      helpful in avoiding overestimation of effectiveness and so reducing the number of
      patients on inadequate treatment. FINANCIAL DISCLOSURE(S): The authors have no
      proprietary or commercial interest in any of the materials discussed in this
      article.

PMID- 21724263
TI  - The effect of adjunctive intravitreal bevacizumab for preventing postvitrectomy
      hemorrhage in proliferative diabetic retinopathy.
AB  - OBJECTIVE: To assess the effects of preoperative and intraoperative intravitreal
      bevacizumab (IVB) injection on the incidence of postoperative vitreous hemorrhage
      (VH) after vitrectomy for proliferative diabetic retinopathy (PDR). DESIGN:
      Prospective, randomized, clinical trial. PARTICIPANTS: One hundred seven eyes of
      91 patients undergoing pars plana vitrectomy (PPV) for the management of PDR
      related complications were enrolled. METHODS: One hundred seven cases were
      assigned randomly to either group 1 (intravitreal 1.25 mg/0.05 ml bevacizumab
      injection 1 to 14 days before PPV), group 2 (intravitreal 1.25 mg/0.05 ml
      bevacizumab injection at the end of PPV), or group 3 (no IVB injection). MAIN
      OUTCOME MEASURES: The primary outcome was the incidence of early (<= 4 weeks) and
      late (> 4 weeks) recurrent VH. Secondary outcome measures were the initial time
      of vitreous clearing (ITVC) and best-corrected visual acuity (BCVA) at 6 months
      after surgery. RESULTS: The incidences of early recurrent VH were 22.2%, 10.8%,
      and 32.4% in groups 1, 2, and 3, respectively (P = 0.087). A subgroup pairwise
      analysis showed significantly decreased early VH incidence in group 2 compared
      with that of group 3 (P = 0.026). The incidences of late recurrent VH were 11.1%,
      16.2%, and 14.7% in groups 1, 2, and 3, respectively (P = 0.813). The ITVC in
      groups 1, 2, and 3 were 26.4 +/- 42.5 days, 10.3 +/- 8.2 days, and 25.2 +/- 26.1
      days, respectively. The ITVC was significantly shorter in group 2 compared with
      that in groups 1 and 3 (P = 0.045 and P = 0.015, respectively). The BCVA at 6
      months after surgery did not differ significantly among the 3 groups (P = 0.418).
      CONCLUSIONS: This study found no substantial evidence to support the adjunctive
      use of preoperative IVB to reduce postoperative recurrence of VH in vitrectomy
      for PDR. For select cases in which adjunctive IVB use is considered,
      intraoperative administration seems to be the better option for reducing
      postoperative VH. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or
      commercial interest in any materials discussed in this article.

PMID- 21724264
TI  - Natural history of drusen morphology in age-related macular degeneration using
      spectral domain optical coherence tomography.
AB  - PURPOSE: To characterize the natural history of drusen using spectral-domain
      optical coherence tomography (SD-OCT) imaging of eyes from patients with
      nonexudative age-related macular degeneration (AMD). DESIGN: Prospective,
      longitudinal, natural history study. PARTICIPANTS: We included 143 eyes of 100
      patients with at least 6 months of follow-up. METHODS: Patients with drusen
      secondary to nonexudative AMD were scanned using the Cirrus SD-OCT instrument.
      Eyes were imaged using the 200 * 200 A-scan raster pattern contained within a 6 *
      6 mm area. Custom software was used to quantify volumetric changes in drusen over
      a period of >= 6 months and for as long as 24 months. Drusen volume and drusen
      area were measured within circular regions centered at the fovea having diameters
      of 3 and 5 mm. The measurements were analyzed using a suitable scale
      transformation. For drusen volume, a cube root transformation strategy was used.
      MAIN OUTCOME MEASURES: Change in drusen volume and area over time. RESULTS: We
      analyzed 143 eyes of 100 patients with 69 eyes followed for 6 months, 106 eyes
      followed for 12 months, 48 eyes followed for 18 months, and 48 eyes followed for
      24 months. The 3 mm circle baseline drusen volume ranged from 0.0009 to 0.7479
      mm(3) or 0.10 to 0.91 mm using the cube root scale. On average, drusen volume and
      drusen area increased over time with the magnitude of the increase dependent on
      the length of follow-up (P = 0.001, 3 mm circle). In the eyes with a decrease in
      drusen volume, the magnitude of this decrease was dependent on the baseline
      drusen volume (P = 0.001, 3 mm circle) and independent of the follow-up interval.
      After 12 months, drusen volume increased in 48% of eyes, remained stable in 40%,
      and decreased in 12%. CONCLUSIONS: Imaging with SD-OCT revealed a dynamic,
      undulating growth pattern for drusen with a tendency for drusen to increase in
      volume and area over time. An appreciation of the quantitative changes in drusen
      volume over time using SD-OCT imaging provides a novel strategy for following
      normal disease progression and for identifying novel clinical trial end points to
      be used when investigating therapies for the treatment of nonexudative AMD.
      FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after
      the references.

PMID- 21724265
TI  - Mood and personality effects in healthy participants after chronic administration
      of sertraline.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are utilised in the
      treatment of a wide range of disorders but the neuropsychological basis of their
      therapeutic efficacy remains unclear. In this study we examine the impact of 3
      weeks administration of sertraline, an SSRI, on mood and personality in a group
      of healthy volunteers to understand the effect of these agents in the absence of
      clinical disorder. METHODS: Thirty-eight healthy women and men, with no personal
      or familial history of Axis I disorder were randomised to receive either a
      placebo or sertraline (50mg/day p.o.) for an average of 23 days, in a double
      blind design. Self-report indices of mood and personality, and genotype (5
      HTTLPR) and sertraline bioavailability were assessed. RESULTS: Chronic
      administration of an SSRI was found to alter mood and personality. The SSRI group
      experienced a significant decrease in negative affect (NA), guilt and
      attentiveness, and significant increases in positive affect (PA), joviality, self
      assurance and serenity. Genotype and bioavailability of sertraline did not
      moderate these findings, however gender did. Only females demonstrated increased
      PA and joviality, and decreased NA; whereas, only males demonstrated decreased
      attentiveness. LIMITATIONS: Greater power and a more specific manipulation of
      serotonergic functioning would help clarify the neurochemical basis of these
      findings. CONCLUSIONS: Results from the current study demonstrate that longer
      term administration of SSRIs alters aspects of mood and personality in the
      absence of disorder. This suggests that these agents have effects on basic
      psychological processes that may in turn form the basis of their therapeutic
      efficacy.

PMID- 21724266
TI  - Molecular characterization and expression of dipeptidase 3, a testis-specific
      membrane-bound dipeptidase: complex formation with TEX101, a germ-cell-specific
      antigen in the mouse testis.
AB  - We previously established an anti-sperm head auto-monoclonal antibody designated
      Ts4. The immunoreactivity of this antibody was also observed in other
      reproduction-related cells, such as testicular germ cells and early embryos,
      suggesting that the Ts4-recognized molecules might play a role in the
      reproductive process. However, the molecular characteristics and functions of the
      antigens warrant further clarification. In this study, we primarily attempted
      identification of the mAb-recognized molecules within the mouse testis. An
      immunoprecipitation method, together with liquid chromatography-tandem mass
      spectrometry, revealed that the testicular immunoprecipitants with Ts4 contained
      dipeptidase 3 (DPEP3), a member of the membrane-bound dipeptidase family. A
      Western blot analysis using an anti-DPEP3 polyclonal antibody established in this
      study showed that this molecule was glycosylated and formed a disulfide-linked
      homodimer within the testis. Expression of DPEP3 protein was observed in the
      testicular germ cells, but not in the Sertoli or interstitial cells, or in any
      other major organs. Although Western blot analysis of testicular proteins
      separated by two-dimensional SDS-PAGE failed to demonstrate binding of Ts4 to
      DPEP3, we found that DPEP3 forms complexes with Ts4-immunoreactive molecules,
      such as TEX101, on the surfaces of spermatocytes, spermatids, and testicular
      spermatozoa. Based on data showing in the present study, further studies
      concerning DPEP3 on the testicular germ cells may help to clarify the molecular
      mechanisms of testicular germ-cell development.

PMID- 21724267
TI  - Relationship of trait impulsivity with clinical presentation in euthymic bipolar
      disorder patients.
AB  - The purpose of this study was to examine trait impulsivity in patients with
      bipolar disorder and explore the possible connections between impulsivity and
      clinical presentation of the illness. Diagnoses were based on the Structured
      Clinical Interview for DSM-IV. The sociodemographic and clinical properties of 71
      patients with bipolar disorder, who were euthymic according to Young Mania Rating
      Scale and Hamilton Depression Scale scores, were recorded. Their trait
      impulsivity was evaluated by using the Barratt Impulsiveness Scale (BIS) and
      impulsivity subscale of the Temperament and Character Inventory, and the results
      were compared with 50 age- and sex-matched healthy controls and among patients
      with different clinical properties. All BIS-11 subscale scores were higher in
      bipolar than in comparison subjects. There were no effects of education and age.
      Elevated BIS-11 scores were associated with predominant depressive polarity,
      longer duration of illness and a history of psychotic mood episodes and suicide
      attempts. These relationships persisted when age, gender, and education were
      taken into account. These results show that after accounting for common
      confounding factors, trait-like impulsivity was substantially higher in subjects
      with bipolar disorder than in nonbipolar comparison subjects and may vary
      according to different clinical presentations.

PMID- 21724268
TI  - Current knowledge on porcine regulatory T cells.
AB  - Regulatory T cells (Tregs) are known in humans and mice from last 15 years, and
      several studies led to a detailed knowledge on their phenotype, functions, and
      role in various immune reactions. In swine, the existence of Tregs was first
      demonstrated in 2008 and research is still at the beginning. Nevertheless, basic
      information regarding phenotype, mechanisms and targets of suppression, as well
      as implications in transplantation and some diseases are available. Purpose of
      this review is to give a brief summary of the current knowledge about porcine
      Tregs.

PMID- 21724269
TI  - Pattern of seroreactivity against feline foamy virus proteins in domestic cats
      from Germany.
AB  - The prevalence of feline foamy virus (FFV, spumaretrovirinae) in naturally
      infected domestic cats ranges between 30 and 80% FFV positive animals depending
      on age, sex and geographical region analyzed. Two serotypes have been reported
      for FFV designated FUV7-like and F17/951-like. Serotype-specific neutralization
      has been shown to correlate with sequence divergence in the surface (SU) domain
      of the envelope protein (Env). We analyzed a serum collection of 262 domestic cat
      sera from Germany using a GST-capture ELISA setup screening for Gag and Bet
      specific antibodies and identified 39% FFV positive animals. Due to the
      heterogeneity of the serological samples, cut-offs for Gag and Bet reactivity had
      to be experimentally determined since application of calculated cut-off values
      yielded some false-positive results; the new cut-off values turned out to be also
      fully applicable to a previous study. Using the already established FUV7 ElpSU
      antigen and the newly cloned and produced F17/951 ElpSU antigen, both consisting
      of the corresponding ectodomains of the envelope leader protein (Elp) and SU
      protein, we aimed at the detection of Env-specific antibodies and discrimination
      between the two known FFV serotypes within the diagnostic FFV ELISA. We validated
      the ElpSU antigens using cat reference sera of known serotype and screened with
      this assay domestic cat sera from Germany. Use of the FUV7- and F17/951 ElpSU
      antigens in ELISA resulted in the detection of Env-specific antibodies in both
      cat reference sera and sera from domestic cats in Germany, but failed to allow
      serotyping at the same time.

PMID- 21724270
TI  - Atrioventricular block 9 days after transcatheter aortic valve implantation.

PMID- 21724271
TI  - Serum carbohydrate antigen 125 has prognostic significance in heart failure, but
      no implications on treatment.

PMID- 21724272
TI  - Adiponectin and progression of arterial stiffness in hypertensive patients.
AB  - BACKGROUND: Recent studies suggest that adiposity is associated with arterial
      stiffness. However, it is unclear which adipokine or what adiposity related
      parameters are related with the progression of arterial stiffness. We
      hypothesized that in hypertensive patients, initial levels of adipokines such as
      adiponectin and resistin are related to the progression of arterial stiffness,
      which has been proven to be associated with increased risk of cardiovascular
      events. METHODS: One hundred forty one consecutive patients with treated
      essential hypertension (81 men, 57.7+/-8.2 years) were enrolled. Pulse wave
      velocity (PWV) was measured at baseline, and after 24 months. Clinical variables
      and laboratory findings at the time of initial enrollment were analyzed to reveal
      the determinants of arterial stiffening. RESULTS: Mean heart to femoral PWV
      (hfPWV) was 992+/-202 cm/s at baseline, and 1021+/-263 cm/s at 24 months follow
      up. hfPWV progressed in seventy two patients (51.1%) during follow up period. In
      patients with hfPWV progression, mean plasma adiponectin level was significantly
      lower than patients with nonprogression (progressor: 5.18+/-3.21 MUg/ml, non
      progressor: 7.02+/-5.19 MUg/ml, p=0.013). Multivariate regression analysis
      revealed plasma adiponectin level to being an independent predictor of hfPWV
      changes (beta=-0.018, p=0.032) when controlled for age, gender, SBP changes, BP
      control and HOMA. CONCLUSIONS: Plasma adiponectin levels are associated with
      progression of arterial stiffness in hypertensive patients. These findings may be
      one explanation for the high association between adiposity and arterial stiffness
      in hypertensive patients.

PMID- 21724273
TI  - Computer-based analysis to optimize prosthesis sizing during aortic valve
      surgery.

PMID- 21724274
TI  - The inability to perform a 6 minute walking test after cardio-thoracic surgery is
      a marker of clinical severity and poor outcome. Data from the ISYDE-2008 Italian
      survey.

PMID- 21724275
TI  - Thromboembolism and ventricular thrombus in non-neuromuscular noncompaction.

PMID- 21724276
TI  - Statins and contrast-induced nephropathy: issues requiring further investigation.

PMID- 21724277
TI  - Mitral stenosis acute pulmonary edema and rheumatic fever pneumonitis: a
      hypothesis to an old enigma.

PMID- 21724278
TI  - EMMPRIN and its ligand cyclophilin A as novel diagnostic markers in inflammatory
      cardiomyopathy.
AB  - BACKGROUND: During inflammatory cardiomyopathy matrix metalloproteinases are
      crucially involved in cardiac remodeling. The aim of the present study was to
      investigate whether the "extracellular matrix metalloproteinase inducer" EMMPRIN
      (CD147) and its ligand Cyclophilin A (CyPA) are upregulated in inflammatory
      cardiomyopathy and may serve as diagnostic markers. Therefore, a series of 102
      human endomyocardial biopsies were analyzed for the expression of EMMPRIN and
      CyPA and correlated with histological and immunohistological findings. METHODS
      AND RESULTS: Endomyocardial biopsies were stained for EMMPRIN and CyPA in
      addition to standard histology (HE, Trichrom) and immunohistological stainings
      (MHC-II, CD68, CD3). 39 (38.2%) biopsies met the immunohistological criteria of
      an inflammatory cardiomyopathy. EMMPRIN, which was predominantly expressed on
      cardiomyocytes, was slightly (but significantly) upregulated in non inflammatory
      cardiomyopathies compared to normal histopathological findings and highly
      upregulated in inflammatory cardiomyopathy compared to both non inflammatory
      cardiomyopathy and normal histopathology. In contrast, CyPA reveals no enhanced
      expression in non inflammatory cardiomyopathies and a highly enhanced expression
      in inflammatory cardiomyopathy, where it is closely associated with leucocytes
      infiltrates. We found a strong correlation between both EMMPRIN and CyPA with the
      expression of MHC-II molecules (correlation coefficient 0.475 and 0.527, p<0.05).
      Moreover, we found a correlation for both EMMPRIN and CyPA with CD68 (correlation
      coefficient 0.393 and 0.387, p<0.05) and CD3 (correlation coefficient 0.360 and
      0.235, p<0.05). CONCLUSION: EMMPRIN is enhanced in both inflammatory and non
      inflammatory cardiomyopathies and can serve as a marker of myocardial remodeling.
      CyPA may represent a novel and specific marker for cardiac inflammation.

PMID- 21724279
TI  - Usefulness of tissue characterization by cardiac magnetic resonance imaging as a
      complementary method for evaluation of cardiac malignant lymphoma.

PMID- 21724280
TI  - Evaluations of land cover risk factors for canine leptospirosis: 94 cases (2002
      2009).
AB  - Associations of land cover/land use variables and the presence of dogs in urban
      vs. rural address locations were evaluated retrospectively as potential risk
      factors for canine leptospirosis in Kansas and Nebraska using Geographic
      Information Systems (GIS). The sample included 94 dogs positive for leptospirosis
      predominantly based on a positive polymerase chain reaction test for leptospires
      in urine, isolation of leptospires on urine culture, a single reciprocal serum
      titer of 12,800 or greater, or a four-fold rise in reciprocal serum titers over a
      2-4 weeks period; and 185 dogs negative for leptospirosis based on a negative
      polymerase chain reaction test and reciprocal serum titers less than 400. Land
      cover features from 2001 National Land Cover Dataset and 2001 Kansas Gap Analysis
      Program datasets around geocoded addresses of case/control locations were
      extracted using 2500m buffers, and the presence of dogs' address locations within
      urban vs. rural areas were estimated in GIS. Multivariate logistic models were
      used to determine the risk of different land cover variables and address
      locations to dogs. Medium intensity urban areas (OR=1.805, 95% C.I.=1.396,
      2.334), urban areas in general (OR=2.021, 95% C.I.=1.360, 3.003), and having
      urban address locations (OR=3.732, 95% C.I.=1.935, 7.196 entire study region),
      were significant risk factors for canine leptospirosis. Dogs regardless of age,
      sex and breed that live in urban areas are at higher risk of leptospirosis and
      vaccination should be considered.

PMID- 21724281
TI  - Analysis of the distributional impact of out-of-pocket health payments: evidence
      from a public health insurance program for the poor in Mexico.
AB  - Many governments have health programs focused on improving health among the poor
      and these have an impact on out-of-pocket health payments made by individuals.
      Therefore, one of the objectives of these programs is to reach the poorest and
      reduce their out-of-pocket expenditure. In this paper we propose the
      distributional poverty impact approach to measure the poverty impact of out-of
      pocket health payments of different health financing policies. This approach is
      comparable to the impoverishment methodology proposed by Wagstaff and van
      Doorslaer (2003) that compares poverty indices before and after out-of-pocket
      health payments. In order to escape the specification of a particular poverty
      index, we use the marginal dominance approach that uses non-intersecting curves
      and can rank poverty reducing health financing policies. We present an empirical
      application of the out-of-pocket health payments for an innovative social
      financing policy implemented in Mexico named Seguro Popular. The paper finds
      evidence that Seguro Popular program has a better distributional poverty impact
      when families face illness when compared to other poverty reducing policies. The
      empirical dominance approach uses data from Mexico in 2006 and considers
      international poverty standards of $2 per person per day.

PMID- 21724282
TI  - Microalgae and biofuels: a promising partnership?
AB  - Microalgae have much higher lipid yields than those of agricultural oleaginosous
      crops, and they do not compromise arable land. Despite this, current microalga
      based processes suffer from several constraints pertaining to the biocatalyst and
      the bioreactor, which hamper technologically and economically feasible scale-up.
      Here, we briefly review recent active research and development efforts worldwide,
      and discuss the most relevant shortcomings of microalgal biofuels. This review
      goes one step further relative to related studies, because it tackles otherwise
      scarcely mentioned issues - for example, heterotrophic versus autotrophic
      metabolism, alkane versus glyceride synthesis, conduction versus bubbling of
      CO(2), and excretion versus accumulation of lipids. Besides promising solutions
      that have been hypothesized and arise from multidisciplinary approaches, we also
      consider less conventional ones. Microalgae and biofuels hold indeed a promising
      partnership, but a fully competitive technology is not expected to be available
      before the end of this decade, because the need for one order of magnitude
      increase in productivity requires development of novel apparatuses and
      transformed cells.

PMID- 21724283
TI  - Adaptive functional image-guided IMRT in pharyngo-laryngeal squamous cell
      carcinoma: is the gain in dose distribution worth the effort?
AB  - BACKGROUND AND PURPOSE: The planning process in radiotherapy (RT) typically
      involves the acquisition of a unique set of CT images - and eventually of
      functional images - which is used for delineation of target volumes (TV) and
      organs at risk (OAR) and for dose calculation. Restricting the delineation and
      dose calculation solely on pre-treatment images is an oversimplification as it is
      only a snapshot of the patient's anatomy. The objectives of the present study
      were (1) to assess the consequences of anatomic modification in dose distribution
      for both TVs and OARs; (2) to assess the potential benefit of adaptive strategies
      using Helical Tomotherapy (HT); and (3) to compare CT-based and FDG-PET-based
      adaptive planning strategies. MATERIALS AND METHODS: Ten patients with H&N SCC
      were imaged before and during concomitant chemo-RT using CT and FDG-PET
      acquisition after a mean dose of 14.2, 24.5, 35.0 and 44.9 Gy. Simultaneous
      integrated boost IMRT planning was performed using HT. We compared (1) the
      planned dose distribution, (2) the delivered dose distributions that took into
      account impact of anatomical modifications on dose distribution, (3) the adaptive
      dose distributions after replanning to take into account the anatomic
      modifications and the anatomic or functional GTV shrinkage. RESULTS: There was an
      increase between the planned and the delivered high dose volumes, which
      correlated with the slope of the GTV shrinkage. The adaptive high dose volumes
      were significantly smaller than the delivered ones. The difference between the
      adaptive and the delivered high dose volume also correlated with the slope of the
      GTV shrinkage. For both parotid glands combined, the delivered D(mean) showed a
      statistical trend for an increase of 4.4% compared to the planned D(mean). For
      the ipsilateral parotid glands, there was a correlation between the D(mean) gain
      and the slope of the GTV shrinkage when an adaptive planning was used. For the
      oral cavity, the adaptive D(mean) was 10% smaller than the delivered ones. For
      the PRV around the spinal cord, there was an increase of about 4.5% between the
      delivered and the planned D(2%). The adaptive planning translated into a decrease
      in D(2%) of 7.2%. The differences between the delivered and planned D(2%) and
      between the adaptive and the delivered D(2%) were correlated with the slope of
      the GTV shrinkage. For the CTV(proph) and PTV(proph) coverage, adaptive strategy
      induced a better dose conformation. No significant difference was observed in the
      various figures of merit between PET-based plan and CT-based isodose
      distributions. CONCLUSIONS: The dose distribution that is actually delivered to
      patients significantly differs from what was planned because of anatomic
      modifications. Adaptive multi-modality IMRT is feasible in H&N tumors and could
      compensate and improve dose distribution. Some useful surrogate criteria or
      "flags" are, however, needed to identify patients who might benefit from an
      adaptive strategy. The optimal adaptive strategy still needs to be defined and
      prospective studies will have to be conducted to address the safety and the
      clinical impact of such approaches on patient outcome.

PMID- 21724284
TI  - Dosimetric study of volumetric modulated arc therapy fields for total marrow
      irradiation.
AB  - BACKGROUND AND PURPOSE: Normal organ toxicity is the leading factor that limits
      dose escalation in total body irradiation for bone marrow transplant (BMT)
      patients. In recent years, total marrow irradiation (TMI) using the helical
      tomotherapy (HT) system is being used as a more targeted form of TBI to treat BMT
      patients. In this study, we evaluated the feasibility of using volumetric
      modulated arc therapy (VMAT) to deliver TMI treatment. MATERIALS AND METHODS: CT
      data sets from two female and two male patients who had received prior total
      marrow and lymphatic irradiation with HT were selected for this study. The target
      volumes included skeletal bones from the skull to the mid-thigh level, major
      lymph nodes, and spleen. Twelve Gray in 8 fractions was prescribed to the target
      volumes. Each VMAT plan was generated with eight arc fields to cover the entire
      target volumes. Both the VMAT and the HT plans were normalized so that 85% of the
      skeletal bone volume was covered by the prescription dose. For each patient, more
      than 20 normal organs were included in plan optimization. RESULTS: Both the VMAT
      and HT plans showed comparable dose coverage to the target volumes and
      significant sparing of normal organ dose. The median dose to the skeletal bone
      volume was 13.4 and 12.6 Gy in the VMAT and HT plans, respectively. The VMAT
      plans showed >10% and >20% reduction of average median dose compared to the HT
      plans in 16 and 11 organs, respectively. The average beam-on time was 628+/-32 s
      and 1122+/-106 s in the VMAT and HT plans, respectively. CONCLUSIONS: The VMAT
      plans provided adequate target dose coverage and normal organ sparing compared to
      helical tomotherapy plans for efficient delivery of total marrow and lymphatic
      irradiation. This study demonstrates that the VMAT technique could be a feasible
      alternative to helical tomotherapy for TMI treatment.

PMID- 21724286
TI  - Developing point of care and high-throughput biological assays for determining
      absorbed radiation dose.
AB  - BACKGROUND AND PURPOSE: Systems are being developed to assess radiation exposure
      based on leukocyte mRNA levels obtained by finger-stick sampling. The goal is to
      provide accurate detection of dose exposures up to 10 Gy for up to 1 week
      following exposure. We previously showed that specific mRNA sequences increase
      expression within an hour of exposure, and some genes continue to show elevated
      expression for at least 24 h. Full duration and dose-dependence of this
      persistence remain to be determined. In the present study, real-time quantitative
      PCR (qPCR) was used to determine changes in gene expression. qPCR can rapidly
      analyze small blood samples and could be adopted into a field-portable instrument
      that provides a radiation dose readout within 30 min. MATERIALS AND METHODS: From
      previous microarray analysis of 21,000 genes expressed in human lymphoblastoid
      cells 4 h post-irradiation (0-4 Gy), 118 genes were selected for evaluation by
      qPCR of gene expression in the leukocytes of human blood irradiated in vitro with
      doses of 0-10 Gy from a Co-60 gamma source at a dose rate of 30 cGy/min. RESULTS:
      Blood from 20 normal healthy human donors yielded many mRNA sequences that could
      be used for radiation dosimetry. We observed four genes with large and persistent
      responses following exposure: ASTN2, CDKN1A, GADD45A, and GDF15. Five genes were
      identified as reliably non-responsive and were suitable for use as endogenous
      controls: DPM1, ITFG1, MAP4, PGK1, and SLC25A36; of these, ITFG1 was used for the
      analyses presented here. A significant dose-responsive increase in expression
      occurred for CDKN1A that was >16-fold at 10 Gy and 3-fold at 0.5 Gy compared to
      pre-irradiation values. CONCLUSIONS: These data show large, selective increases
      in mRNA transcript levels that persist for at least 48 h after single exposures
      between 0.5 and 10 Gy. Stable, non-responsive mRNA sequences for use as
      endogenous controls were also identified. These results indicate that following
      further study to establish the most reproducible gene and dose-response models
      under a wide range of conditions in vivo, rapid real-time qPCR on blood samples
      could potentially be used to establish biologically-effective dosimetry from
      either accidental irradiation or clinical radiotherapy.

PMID- 21724287
TI  - Stereotactic radiotherapy of histologically proven inoperable stage I non-small
      cell lung cancer: patterns of failure.
AB  - BACKGROUND AND PURPOSE: To report patterns of failure of stereotactic body
      radiation therapy (SBRT) in inoperable patients with histologically confirmed
      stage I NSCLC. MATERIALS AND METHODS: Ninety-two inoperable patients (median age:
      75 years) with clinically staged, histologically proven T1 (n=31) or T2 (n=61),
      N0, M0 non-small cell lung cancer (NSCLC) were included in this study. Treatment
      consisted of 3-5 fractions with 7-15 Gy per fraction prescribed to the 60%
      isodose. RESULTS: Freedom from local recurrence at 1, 3 and 5 years was 89%, 83%
      and 83%, respectively. All 10 local failures were observed in patients with T2
      tumors. Isolated regional recurrence was observed in 7.6%. The crude rate of
      distant progression was 20.7%. Overall survival at 1, 3, and 5 years was 79%, 38%
      and 17% with a median survival of 29 months. Disease specific survival at 1, 3,
      and 5 years was 93%, 64% and 48%. Karnofsky performance status, T stage, gross
      tumor volume and tumor location had no significant impact on overall and disease
      specific survival. SBRT was generally well tolerated and all patients completed
      therapy as planned. CONCLUSION: SBRT for stage I lung cancer is very well
      tolerated in this patient cohort with significant cardiopulmonal comorbidity and
      results in excellent local control rates, although a considerable portion
      develops regional and distant metastases.

PMID- 21724288
TI  - Tumour-infiltrating CD11b+ myelomonocytes and response to fractionated
      irradiation of human squamous cell carcinoma (hSCC) xenografts.
AB  - PURPOSE: Bone marrow derived CD11b+ myelomonocytes have been shown to be
      recruited by the tumour and to promote tumour regrowth after irradiation. Here we
      investigated in a panel of well characterised hSCC tumour models the number of
      tumour-infiltrating CD11b+ cells and the association with response to clinically
      relevant fractionated irradiation. METHODS: Six hSCC tumour models (UT-SCC-5, 
      14, -15, XF354, FaDu, SAS) xenografted in nude mice were excised after injection
      of pimonidazole hypoxia marker before irradiation and after 5 and 10 fractions.
      In parallel, TCD(50) (dose to cure 50% of the tumours) assays were performed to
      determine the response to 30 fractions within 6 weeks. The TCD(50) values have
      been previously published [1]. Double staining of CD11b and pimonidazole was
      performed using immunofluorescence. CD11b+ cells were counted in viable
      pimonidazole-negative areas (non-hypoxic) and pimonidazole-positive areas
      (hypoxic) of whole tumour cross-sections. RESULTS: The median number of tumour
      infiltrating CD11b+ cells either decreased or remained unchanged after 5 and 10
      fractions in most of the tumour models. The density of CD11b+ cells in hypoxic
      areas was similar or lower than in non-hypoxic regions independently on treatment
      in majority of the tumour models. After 10 fractions the median CD11b+ cell
      density was significantly associated with the TCD(50) values after 30 fractions.
      CONCLUSION: The data from our exploratory study suggest that tumour-infiltrating
      CD11b+ cells may contribute to local tumour control after fractionated
      irradiation, which supports to further study their prognostic value and to
      evaluate specific myelomonocyte targeting strategies to overcome radiation
      resistance.

PMID- 21724289
TI  - Insulin glulisine may ameliorate nocturnal hypoglycemia related to insulin
      antibody--a case report.

PMID- 21724290
TI  - A new prize system for drug innovation.
AB  - We propose a new prize (reward) system for drug innovation which pays a price
      based on the value of health benefits accrued over time. Willingness to pay for a
      unit of health benefit is determined based on the cost-effectiveness ratio of
      palliative/nursing care. We solve the problem of limited information on the value
      of health benefits by mathematically relating reward size to the uncertainty of
      information including information on potential drug overuse. The proposed prize
      system offers optimal incentives to invest in research and development because it
      rewards the innovator for the social value of drug innovation. The proposal is
      envisaged as a non-voluntary alternative to the current patent system and reduces
      excessive marketing of innovators and generic drug producers.

PMID- 21724291
TI  - Automatic multi-modal intelligent seizure acquisition (MISA) system for detection
      of motor seizures from electromyographic data and motion data.
AB  - The objective is to develop a non-invasive automatic method for detection of
      epileptic seizures with motor manifestations. Ten healthy subjects who simulated
      seizures and one patient participated in the study. Surface electromyography
      (sEMG) and motion sensor features were extracted as energy measures of
      reconstructed sub-bands from the discrete wavelet transformation (DWT) and the
      wavelet packet transformation (WPT). Based on the extracted features all data
      segments were classified using a support vector machine (SVM) algorithm as
      simulated seizure or normal activity. A case study of the seizure from the
      patient showed that the simulated seizures were visually similar to the epileptic
      one. The multi-modal intelligent seizure acquisition (MISA) system showed high
      sensitivity, short detection latency and low false detection rate. The results
      showed superiority of the multi-modal detection system compared to the uni-modal
      one. The presented system has a promising potential for seizure detection based
      on multi-modal data.

PMID- 21724293
TI  - Heterology expression of the sweet pepper CBF3 gene confers elevated tolerance to
      chilling stress in transgenic tobacco.
AB  - Various studies have confirmed that the CBF (C-repeat binding factor) family of
      transcription factors has a key role in regulating many plants' responses to cold
      stress. Here we isolated CBF3 from sweet pepper (Capsicum frutescens). Green
      fluorescent protein (GFP) fusion protein of CfCBF3 was targeted to the nucleus of
      the onion epidermis cell. RNA gel blot analysis indicated that CfCBF3 was
      expressed in leaves of sweet pepper and the expression was induced by low
      temperature, drought and salinity stresses but not by ABA. Overexpression of
      CfCBF3 under the control of the CaMV35S promoter in tobacco induced expression of
      orthologs of CBF3-targeted genes and increased chilling tolerance without a dwarf
      phenotype. Indeed it also led to multiple biochemical and physiological changes
      associated with chilling stress. Higher levels of proline (Pro) and soluble
      sugars and lower content of reactive oxygen species (ROS) were observed in
      transgenic plants. Our results demonstrated that the increase in total
      unsaturated fatty acids, especially in phosphatidylglycerol (PG) was detected by
      overexpression of CfCBF3. During exposure to chilling stress, the transgenic
      lines were less susceptible to chilling-induced photoinhibition than wild-type
      (WT) plants. These results suggest that overexpression of CfCBF3 led to
      modification of the fatty acid unsaturation and alleviated the injuries under
      chilling stress.

PMID- 21724294
TI  - Nephrogenic systemic fibrosis: clinicopathological definition and workup
      recommendations.
AB  - BACKGROUND: The condition that came to be known as nephrogenic systemic fibrosis
      (NSF) was first reported in 2000 and, in 2001, was termed "nephrogenic fibrosing
      dermopathy." Since then, NSF has been the subject of a wide-ranging
      multidisciplinary medical investigation that has proven an indisputable link to
      renal disease and a compelling association with the increasing use of gadolinium
      containing magnetic resonance imaging contrast agents in the renally impaired.
      OBJECTIVE: Although precise causation and risk factors continue to be elucidated,
      the need for reproducible prospective epidemiologic data demands clear and
      objective criteria for the diagnosis of NSF. METHODS: Experts in NSF diagnosis
      used their experience and the resources of the Yale International NSF Registry to
      develop a clinicopathological diagnostic system for NSF. RESULTS: A consensus
      scoring system incorporating a clinical and histopathological atlas was devised
      to guide and standardize the evaluation and diagnosis of NSF. LIMITATIONS: There
      is no laboratory test that can be used as a gold standard to diagnose NSF. To
      overcome this, we relied on classic clinicopathological presentations, published
      sources, and consensus clinical expertise to ensure the integrity of the study
      population. CONCLUSION: The clinicopathological definition of NSF provides
      guidance to physicians for the evaluation and diagnosis of NSF. Clinical,
      laboratory, and histopathological features comprise a schema that excludes
      conditions mimicking NSF while facilitating its reproducible and accurate
      diagnosis, even among physicians with little prior clinical experience with this
      entity. This definition can serve as a working diagnostic standard for future
      research and as the basis for adjudicating borderline cases.

PMID- 21724295
TI  - Risk factors for nosocomial bacteraemia in intensive care units vary depending on
      causative agents: results of a prospective surveillance study from 2003 to 2006.

PMID- 21724296
TI  - Diagnostic testing for Clostridium difficile: a comprehensive survey of
      laboratories in England.
AB  - Recent studies have shown poor performance of commonly used toxin enzyme
      immunoassays (EIAs) for laboratory testing for Clostridium difficile infection
      (CDI). In 2009-2010, the UK Health Protection Agency and the European Society of
      Clinical Microbiology and Infectious Diseases stated that toxin EIA testing alone
      is suboptimal, and recommended a two-step testing protocol (i.e. screening with
      one method and confirming the results with another method). All acute English
      National Health Service trusts were surveyed to determine their testing methods
      and positivity rates using freedom of information requests. Replies were received
      from 168 of 170 trusts (99% response rate). Seventy percent of trusts were using
      a toxin EIA as a standalone testing method, with positive predictive values
      (PPVs) as low as 20% in some cases. The mean positivity rate decreased from 6.45%
      in 2008 to 4.47% in 2009, which will have a negative effect on the PPVs of these
      tests. The UK Department of Health publishes CDI rates as a measure of quality of
      care and good infection control practice. However, this may not provide valid
      comparisons because of the wide disparity between testing methods. The present
      study demonstrates wide variation in testing practices for CDI in England, and
      laboratories should reconsider their current testing strategies.

PMID- 21724298
TI  - [Effective measures for inefficient].

PMID- 21724297
TI  - Adalimumab is effective in long-term real life clinical practice in both luminal
      and perianal Crohn's disease. The Madrid experience.
AB  - OBJECTIVE: To evaluate effectiveness and safety of adalimumab in CD patients of
      the Madrid area and identify predictors of response. METHODS: Multicenter
      retrospective survey of all CD patients treated with adalimumab in 9 hospitals of
      the Madrid area (Spain). Univariate and multivariate analysis of predictors of
      response was performed. RESULTS: 174 patients included (50% males) with a median
      follow-up of 40 weeks. 30% had active perianal fistulizing disease at the
      beginning of the therapy with adalimumab. 59% had been previously treated with
      infliximab, being the lost of response (42.2%) the most frequent cause of
      withdrawal of the drug. 33% of patients needed dose escalation from every-other
      week to every week. The median time for this dose escalation was 33 weeks (range
      2-120). The percentages of complete response at 4 weeks, 6 months and end of
      follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal
      disease respectively. The prevalence of adverse events was 18% (most frequent
      was: 5 abscesses) causing the withdrawal of the drug in 21% of them. CONCLUSIONS:
      Adalimumab is effective and safe for the management of CD, even in refractory
      cases to infliximab.

PMID- 21724299
TI  - [Evaluation of therapeutic inertia in lipid lowering treatment of primary care
      patients with high cardiovascular risk].

PMID- 21724300
TI  - [Bilateral carotid occlusion and progressive stenosis of vertebral arteries after
      radiotherapy in a young patient].

PMID- 21724301
TI  - Hypertrophic olivary degeneration secondary to a Guillain-Mollaret triangle
      lesion.

PMID- 21724302
TI  - Dopaminergic agonists in Parkinson's disease.
AB  - BACKGROUND: Non-ergoline dopamine agonists (DA) are effective treatments for
      Parkinson's disease (PD). This review presents the pharmacology, evidence of
      efficacy and safety profile of pramipexole, ropinirole, and rotigotine, and
      practical recommendations are given regarding their use in clinical practice.
      RESULTS: Extended-release formulations of pramipexole and ropinirole and
      transdermal continuous delivery rotigotine patches are currently available; these
      may contribute to stabilising of plasma levels. In early PD, the three drugs
      significantly improve disability scales, delay time to dyskinesia and allow a
      later introduction of levodopa. In late PD they reduced total 'off'-time,
      improved Unified Parkinson's Disease Rating Scale (UPDRS) in both 'on' and 'off'
      state and allowed a reduction in total levodopa dosage. A significant improvement
      in quality of life scales has also been demonstrated. Extended-release
      formulations have proved to be non-inferior to the immediate release formulations
      and are better tolerated (ropinirole). Despite a generally good safety profile,
      serious adverse events, such as impulse control disorder and sleep attacks, need
      to be routinely monitored. Although combination therapy has not been addressed in
      scientific literature, certain combinations, such as apomorphine and another DA,
      may be helpful. Switching from one DA to another is feasible and safe, although
      in the first days an overlap of dopaminergic side effects may occur. When
      treatment with DA is stopped abruptly, dopamine withdrawal syndrome may present.
      Suspending any DA, especially pramipexole, has been linked to onset of apathy,
      which may be severe. CONCLUSIONS: New non-ergotine DAs are a valuable option for
      the treatment of both early and late PD. Despite their good safety profile,
      serious adverse effects may appear; these effects may have a pathoplastic effect
      on the course of PD and need to be monitored.

PMID- 21724303
TI  - Synthesis, characterization and pharmacological activity of 4-{[1-substituted
      aminomethyl-4-arylideneamino-5-sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}
      2H-1,4-benzothiazin-3(4H)-ones.
AB  - A new series of Schiff and Mannich bases derivatives (6) of 4-[(4-amino-5
      sulfanyl-4H-1,2,4-triazol-3-yl)methyl]-2H-1,4-benzothiazin-3(4H)-one (4), derived
      from (3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)acetic acid (3) were
      synthesized. The structures of all newly synthesized compounds were elucidated by
      elemental analysis, IR, (1)H NMR and mass spectral data. Synthesized compounds
      were evaluated for their anti-inflammatory and analgesic activity. Among the
      tested compounds, the (3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)acetic acid (3)
      possess analgesic activity comparable to that of pentazocine; activity decreased
      on derivatization of the carboxylic acid group. However the anti-inflammatory
      activity of (3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)acetic acid (3) increased
      by derivatization of the carboxylic acid group and some of the compounds showed
      anti-inflammatory activity comparable to that of indomethacin.

PMID- 21724304
TI  - Synthesis, characterization and anticancer studies of mixed ligand
      dithiocarbamate palladium(II) complexes.
AB  - Six mixed ligand dithiocarbamate Pd(II) complexes (1-6) of general formula
      [(DT)Pd(PR(3))Cl], where DT = dimethyldithiocarbamate (1, 5),
      diethyldithiocarbamate (2, 3), dicyclohexyldithiocarbamate (4), bis(2
      methoxyethyl)dithiocarbamate (6); PR(3) = benzyldiphenylphosphine (1), diphenyl-2
      methoxyphenylphosphine (2), diphenyl-p-tolylphosphine (3), diphenyl-m
      tolylphosphine (4), tricyclohexylphosphine (5), diphenyl-2-pyridylphosphine (6)
      have been synthesized and characterised using Elemental analysis, FT-IR, Raman
      and multinuclear magnetic resonance (NMR) spectroscopy. Compounds 1 and 2 were
      also characterized by single crystal X-ray diffraction technique (XRD). The XRD
      study reveals that the Pd(II) moiety has a pseudo square-planar geometry, in
      which two positions are occupied by the dithiocarbamate ligand in a bidentate
      fashion, while at the remaining two positions organophosphine and chloride are
      present. The anticancer activity of the synthesized metallodrugs was checked
      against DU145 human prostate carcinoma (HTB-81) cells, the IC(50) values indicate
      that the compounds are highly active against these cells. These Pd(II) complexes
      also show moderate antibacterial activity against gram positive and gram negative
      bacteria.

PMID- 21724305
TI  - Synthesis and Na+/H+ exchanger inhibitory activity of benzoylguanidine
      derivatives.
AB  - Twenty-two compounds of substituted benzoylguanidine derivatives were designed
      and synthesized as potent NHE1 inhibitors. Twelve compounds showed more potent
      NHE1 inhibitory activity than cariporide. The activities of compounds 7e, 7h and
      7j (IC(50) = 0.073 +/- 0.021, 0.084 +/- 0.012 and 0.068 +/- 0.021 nmol/L,
      respectively) were two orders of magnitude higher than that of cariporide (30.7
      +/- 2.5 nmol/L). Myocardial cells in vitro screening showed 7j had highlighted
      protective effect on cardiomyocytes subjected to hypoxia/reoxygenation. Thus it
      is valuable for further investigation.

PMID- 21724306
TI  - [Stroke in a 59-year-old man].

PMID- 21724307
TI  - A work-based educational intervention to support the development of personal
      resilience in nurses and midwives.
AB  - A work-based educational programme was the intervention used in a collective case
      study aiming to develop, strengthen and maintain personal resilience amongst
      fourteen nurses and midwives. The participants attended six, monthly workshops
      and formed a participatory learning group. Post-intervention, participants
      reported positive personal and professional outcomes, including enhanced self
      confidence, self-awareness, communication and conflict resolution skills. They
      strengthened relationships with their colleagues, enabling them to build helpful
      support networks in the workplace. The intervention used new and innovative ways
      of engaging nurses and midwives exhibiting the effects of workplace adversity -
      fatigue, pressure, stress and emotional labour. Participants were removed from
      their usual workplace environment and brought together to engage in critical
      reflection, experiential learning and creativity whilst also learning about the
      key characteristics and strategies of personal resilience. Participants'
      experiences and skills were valued and respected; honest airing of the
      differences within the group regarding common workplace issues and concerns was
      encouraged. The new contribution of this intervention for nursing and midwifery
      education was supporting the learning experience with complementary therapies to
      improve participants' wellbeing and reduce stress.

PMID- 21724308
TI  - Acute myeloid leukemia with mutated nucleophosmin (NPM1): any hope for a targeted
      therapy?
AB  - Acute myeloid leukemia (AML) carrying nucleophosmin (NPM1) mutations displays
      distinct molecular and clinical-pathological features that led to its inclusion
      as provisional entity in 2008 WHO classification of myeloid neoplasms. Since NPM1
      mutations behave as a founder genetic lesion in AML, they could be an attractive
      target for therapeutic intervention. Here, we discuss the potential for
      developing targeted therapies for NPM1-mutated AML with focus on: (i) interfering
      with the abnormal traffic of the NPM1 leukemic mutant, i.e., its cytoplasmic
      dislocation; (ii) disrupting the nucleolar structure/function by interfering with
      residual wild-type nucleophosmin and other nucleolar components acting as hub
      proteins; and (iii) evaluating the activity of epigenetic drugs (e.g., 5
      azacytidine) or agents acting on differentiation and apoptosis. As quantitative
      assessment of NPM1 mutated transcript copies now provides the means to measure
      minimal residual disease, we also discuss the potential for intervening in NPM1
      mutated AML before overt hematological relapse occurs (so-called pre-emptive
      therapy).

PMID- 21724309
TI  - Chronic toxicity of ZnO nanoparticles, non-nano ZnO and ZnCl2 to Folsomia candida
      (Collembola) in relation to bioavailability in soil.
AB  - The chronic toxicity of zinc oxide nanoparticles (ZnO-NP) to Folsomia candida was
      determined in natural soil. To unravel the contribution of particle size and free
      zinc to NP toxicity, non-nano ZnO and ZnCl(2) were also tested. Zinc
      concentrations in pore water increased with increasing soil concentrations, with
      Freundlich sorption constants K(f) of 61.7, 106 and 96.4 l/kg (n = 1.50, 1.34 and
      0.42) for ZnO-NP, non-nano ZnO and ZnCl(2) respectively. Survival of F. candida
      was not affected by ZnO-NP and non-nano ZnO at concentrations up to 6400 mg Zn/kg
      d.w. Reproduction was dose-dependently reduced with 28-d EC50s of 1964, 1591 and
      298 mg Zn/kg d.w. for ZnO-NP, non-nano ZnO and ZnCl(2), respectively. The
      difference in EC50s based on measured pore water concentrations was small (7.94
      16.8 mg Zn/l). We conclude that zinc ions released from NP determine the observed
      toxic effects rather than ZnO particle size.

PMID- 21724310
TI  - Structural determinants of adolescent girls' vulnerability to HIV: views from
      community members in Botswana, Malawi, and Mozambique.
AB  - In sub-Saharan Africa, adolescent girls are three to four times more likely than
      adolescent boys to be living with HIV/AIDS. A literature review revealed only
      four studies that had examined HIV vulnerability from the perspective of
      community members. None of the studies focused specifically on adolescent girls.
      To fill this gap, in 2008 12 focus group discussions were held in selected peri
      urban and rural sites in Botswana, 12 in Malawi, and 11 in Mozambique to identify
      factors that render girls vulnerable to HIV infection from the community members'
      perspective. The preponderance of comments identified structural factors-
      insufficient economic, educational, socio-cultural, and legal support for
      adolescent girls--as the root causes of girls' vulnerability to HIV through
      exposure to unprotected sexual relationships, primarily relationships that are
      transactional and age-disparate. Community members explicitly called for policies
      and interventions to strengthen cultural, economic, educational, and legal
      structures to protect girls, recognized community members' responsibility to take
      action, and requested programs to enhance adult-child communication, thus
      revealing an understanding that girls' vulnerability is multi-level and multi
      faceted, so must be addressed through a comprehensive approach to HIV prevention.

PMID- 21724311
TI  - More than a dance: the production of sexual health risk in the exotic dance clubs
      in Baltimore, USA.
AB  - Women who exchange sex for money, drugs, or goods are disproportionately infected
      with HIV and have high rates of illicit drug use. A growing body of research has
      underscored the primacy of environmental factors in shaping individual behaviors.
      HIV/STI rates among sex workers are influenced by environmental factors such as
      the physical (e.g., brothel) and economic (e.g., increased pay for unsafe sex)
      context in which sex work occurs. Exotic dance clubs (EDCs) could be a risk
      environment that is epidemiologically significant to the transmission of HIV/STIs
      among vulnerable women, but it is a context that has received scant research
      attention. This study examines the nature of the physical, social, and economic
      risk environments in promoting drug and sexual risk behaviors. Structured
      observations and semi-structured qualitative interviews (N = 40) were conducted
      with club dancers, doormen, managers, and bartenders from May through August,
      2009. Data were analyzed inductively using the constant comparative method common
      to grounded theory methods. Atlas-ti was used for data analysis. Dancers began
      working in exotic dance clubs primarily because of financial need and lack of
      employment opportunities, and to a lesser extent, the need to support illicit
      drug habits. The interviews illuminated the extent to which the EDCs' physical
      (e.g., secluded areas for lap dances), economic (e.g., high earnings from dancers
      selling sex), and social (e.g., prevailing social norms condoning sex work)
      environments facilitated dancers' engaging in sex work. Drug use and alcohol use
      were reported as coping mechanisms in response to these stressful working
      conditions and often escalated sexual risk behaviors. The study illuminated
      characteristics of the environment that should be targeted for interventions.

PMID- 21724312
TI  - Maternal education and adverse birth outcomes among immigrant women to the United
      States from Eastern Europe: a test of the healthy migrant hypothesis.
AB  - Immigrant women to the U.S. often have more favorable birth outcomes than their
      native-born counterparts, including lower rates of preterm birth and low birth
      weight, a phenomenon commonly attributed to a healthy migrant effect. However,
      this effect varies by ethnicity and country of origin. No previous study has
      examined birth outcomes among immigrants from the post-Communist countries of
      Eastern Europe, a group which includes both economic migrants and conflict
      refugees. Using data on 253,363 singletons births from New York City during 1995
      2003 we examined the risk of preterm birth (PTB) (<37 weeks) or delivering a term
      small-for-gestational-age (SGA) infant among immigrants from Russia and Ukraine
      (RU), Poland, and former Yugoslavia Republics (FYR) relative to US-born non
      Hispanic whites (NHW). Women in all three Eastern European groups had
      significantly later entry into prenatal care, were more likely to be Medicaid
      recipients, and had lower educational attainment than US-born NHW. In binomial
      regression analyses adjusting for age, education, parity, and pre-pregnancy
      weight, women from RU and FYR had lower risk of PTB than US-born NHW, whereas
      women from Poland had similar risk. Lower SGA risk was found among women from
      Poland and FYR, but not RU. When stratified by education, women with <12 years of
      education from all Eastern European groups had a reduced risk of PTB relative to
      US-born NHW. An educational gradient in PTB and SGA risk was less pronounced in
      all Eastern European groups compared to US-born NHW. The healthy migrant effect
      is present among immigrants from Eastern Europe to the U.S., especially among
      women with less education and those from the former Yugoslavia, a group that
      included many conflict refugees.

PMID- 21724313
TI  - Beyond a catalogue of differences: a theoretical frame and good practice
      guidelines for researching sex/gender in human health.
AB  - Extensive medical, public health, and social science research have focused on
      cataloguing male-female differences in human health. Unfortunately, much of this
      research unscientifically and unquestionably attributes these differences to
      biological causes--as exemplified in the Institute of Medicine's conclusion that
      "every cell has a sex." In this manuscript we theorize the entanglement of sex
      and gender in human health research and articulate good practice guidelines for
      assessing the role of biological processes--along with social and biosocial
      processes--in the production of non-reproductive health differences between and
      among men and women. There are two basic tenets underlying this project. The
      first is that sex itself is not a biological mechanism and the second is that
      "sex" and "gender" are entangled, and analyses should proceed by assuming that
      measures of sex are not pristine, but include effects of gender. Building from
      these tenets--and using cardiovascular disease as a consistent example--we
      articulate a process that scientists and researchers can use to seriously and
      systematically assess the role of biology and social environment in the
      production of health among men and women. We hope that this intervention will be
      one further step toward understanding the complexity and nuance of health
      outcomes, and that this increased knowledge can be used to improve human health.

PMID- 21724314
TI  - Safety of intravenous sedation administered by the operating oral surgeon: the
      second 7 years of office practice.
AB  - PURPOSE: This follow-up study provides an additional 7 years of data (December
      2001 through November 2008) pertaining to complications that occurred in patients
      who received intravenous sedation in the practice of a single board-certified
      oral and maxillofacial surgeon. Together with the previously published 7 years of
      data (December 1994 through November 2001), this study summarizes the frequency
      of various complications encountered in patients sedated intravenously by the
      surgeon over a 14-year period. MATERIALS AND METHODS: The files of intravenous
      sedation cases from the second 7-year period were reviewed for complications.
      These data were then compared, contrasted, and combined with the previously
      published sedation cases from the first 7 years. RESULTS: A total of 3,320
      sedations were performed by the surgeon during this second 7-year period, with
      only 1.57% of patients having complications (52 patients having 60 adverse
      events). These results showed a slight decline in the frequency of complications.
      Over the entire 14-year period of study, a total of 6,209 sedations were
      performed by the surgeon, with 1.96% of patients having complications (122
      patients having 137 adverse events). There were no deaths, and no patients
      required emergency transport to a hospital. CONCLUSIONS: The results of this
      follow-up study confirm the previous findings. The administration of intravenous
      sedation by the operating surgeon for outpatient oral surgery is safe, with a low
      frequency of complications. Numerous patients were also made aware of previously
      undiagnosed medical problems, improving overall patient health.

PMID- 21724315
TI  - Factors that determine intraoperative blood loss in bimaxillary osteotomies and
      the need for preoperative blood preparation.
AB  - PURPOSE: To define factors that influence blood loss in bimaxillary osteotomies
      and the need for blood preparation at the Faculty of Dentistry, Mahidol
      University, Bangkok, Thailand. PATIENTS AND METHODS: We retrospectively studied
      208 patients who underwent bimaxillary osteotomies during 2005 to 2009. Possible
      factors for intraoperative blood loss such as age, body weight, gender, operative
      time, experience of the surgeons, and different operative procedures were
      statistically analyzed. RESULTS: Female patients had a significantly higher
      percentage of blood loss from allowable blood loss than male patients (P = .006).
      Experience of the surgeons had a significant influence on blood loss (P = .02)
      and operative time (P < .001). No significant difference in blood loss was found
      among the 4 groups classified by operation (P = .852). Simple regression analysis
      showed a significantly positive correlation between blood loss and duration of
      operation (R(2) = 0.15, P < .001). There was no correlation between blood loss
      and patient age (P = .35). CONCLUSION: The factors that influence blood loss
      include patient gender, experience of the surgeon, and operative time. Blood
      preparation should be considered in women, especially small individuals in whom a
      long operative time is expected and who are being operated on by an inexperienced
      surgeon. Because of the low rate of transfusion, a group-and-save policy is
      appropriate.

PMID- 21724316
TI  - A structural model of perfusion and oxygenation in low-flow states.
AB  - BACKGROUND: Recent investigations underscore the critical importance of
      ventilation strategies on resuscitation outcomes. In low perfusion states, such
      as cardiac arrest and traumatic shock, the rise in intrathoracic pressure that
      accompanies positive-pressure ventilation can significantly impede venous return
      and lead to a decrease in cardiac output. The optimal ventilation strategy in
      these "low-flow" states remains unclear. OBJECTIVE: To create a mathematical
      model of perfusion and oxygenation to predict the effects of PPV with both
      normotension and hypotension. METHODS: The lung pressure-volume relationship was
      modeled using a novel formula allowing manipulation of various lung
      characteristics. A separate formula was then derived to predict mean
      intrathoracic pressure (MITP) for specific minute ventilation values using the
      pressure-volume formula. The addition of positive end-expiratory pressure was
      also modeled. Finally, a formula was derived to model oxygen absorbance as a
      function of alveolar surface area and flow based on ventilation rate and MITP.
      RESULTS: Mathematical models of the lung pressure-volume relationship, MITP, and
      absorbance were successfully derived. Manipulation of total lung capacity,
      compliance, upper and lower inflection points, positive end-expiratory pressure,
      and minute ventilation allowed prediction of optimal ventilation rate and tidal
      volume for a normal lung and with various abnormal characteristics to simulate
      particular disease states, such as acute respiratory distress syndrome (ARDS).
      For a normal lung, ventilation rates of 4-6 breaths/min with higher tidal volumes
      (15-20 mL/kg) resulted in the lowest predicted MITP values (5 cm H(2)O) and the
      highest absorbance. The input of lung parameters that would simulate ARDS
      resulted in optimal ventilation rates of 10-12 breaths/min with lower tidal
      volumes (8-10 mL/kg) and higher predicted MITP values (10-15 cmH(2)O).
      CONCLUSIONS: A mathematical model of ventilation was successfully derived
      allowing manipulation of multiple pulmonary physiological variables to predict
      MITP and potentially identify optimal ventilation strategies. This model suggests
      the use of lower ventilation rates and larger tidal volumes to minimize the
      hemodynamic effects of positive pressure ventilation in patients with
      hypoperfusion but normal lung characteristics.

PMID- 21724317
TI  - Poor chest compression quality with mechanical compressions in simulated
      cardiopulmonary resuscitation: a randomized, cross-over manikin study.
AB  - INTRODUCTION: Mechanical chest compression devices are being implemented as an
      aid in cardiopulmonary resuscitation (CPR), despite lack of evidence of improved
      outcome. This manikin study evaluates the CPR-performance of ambulance crews, who
      had a mechanical chest compression device implemented in their routine clinical
      practice 8 months previously. The objectives were to evaluate time to first
      defibrillation, no-flow time, and estimate the quality of compressions. METHODS:
      The performance of 21 ambulance crews (ambulance nurse and emergency medical
      technician) with the authorization to perform advanced life support was studied
      in an experimental, randomized cross-over study in a manikin setup. Each crew
      performed two identical CPR scenarios, with and without the aid of the mechanical
      compression device LUCAS. A computerized manikin was used for data sampling.
      RESULTS: There were no substantial differences in time to first defibrillation or
      no-flow time until first defibrillation. However, the fraction of adequate
      compressions in relation to total compressions was remarkably low in LUCAS-CPR
      (58%) compared to manual CPR (88%) (95% confidence interval for the difference:
      13-50%). Only 12 out of the 21 ambulance crews (57%) applied the mandatory
      stabilization strap on the LUCAS device. CONCLUSIONS: The use of a mechanical
      compression aid was not associated with substantial differences in time to first
      defibrillation or no-flow time in the early phase of CPR. However, constant but
      poor chest compressions due to failure in recognizing and correcting a
      malposition of the device may counteract a potential benefit of mechanical chest
      compressions.

PMID- 21724319
TI  - Epstein-Barr virus and breast cancer: serological study in a high-incidence area
      of nasopharyngeal carcinoma.
AB  - We investigated IgA and IgG levels against EBV viral capsid antigen (VCA) and
      nuclear antigen-1 (EBNA-1) in serum of 223 women with breast cancer (BC) and 309
      controls in Guangzhou, China. VCA IgA levels were significantly associated with
      an elevated risk of BC, with adjusted ORs (95%CIs) of 1.70 (1.05-2.76)
      (seropositivity) and 2.21 (1.11-4.40) (unit increases in OD value). This
      association was stronger among young, lean, and HER2+ women. The EBNA-1 IgA
      levels in OD value, but not seropositivity, were associated with an increased
      risk of BC among ER+, PR+, and HER2+ patients. None of the IgG variables was
      related to BC. These results suggest the EBV association with BC in an endemic
      area of nasopharyngeal carcinoma.

PMID- 21724320
TI  - Retreatment of silicon slurry by membrane processes.
AB  - The purpose of the present study is to develop a process to regenerate the polish
      liquid used in Chemical and Mechanical Polishing (CMP), called "slurry", and more
      specifically Silicon CMP slurry. Physico-chemical analyses show a considerable
      dilution of slurry through washing waters used in polishing. Thus, this effluent
      has been characterised for a better identification of the deviations from the
      slurry of reference (Point Of Use). Hence, the principle is to regenerate this
      effluent by membrane processes. The ultrafiltration results obtained at
      laboratory scale have led to the development of an industrial prototype. An
      optimal utilisation of this treatment allows completing a two-step process: the
      reconcentration by ultrafiltration and a chemical adjustment by addition of
      concentrated slurry. A stable behaviour of the slurry at the different steps of
      the process has been observed. Polishing results are similar with retreated and
      POU slurries. Furthermore, the functioning at industrial scale permits to
      maintain the performances obtained on the laboratory pilot.

PMID- 21724321
TI  - Strong adsorption of chlorotetracycline on magnetite nanoparticles.
AB  - In this work, environmentally friendly magnetite nanoparticles (Fe(3)O(4) MNPs)
      were used to adsorb chlorotetracycline (CTC) from aqueous media. Fe(3)O(4) MNPs
      exhibit ultrahigh adsorption ability to this widely used antibiotic. The
      adsorption behavior of CTC on Fe(3)O(4) MNPs fitted the pseudo-second-order
      kinetics model, and the adsorption equilibrium was achieved within 10h. The
      maximum Langmuir adsorption capacity of CTC on Fe(3)O(4) (476 mg g(-1)) was
      obtained at pH 6.5. Thermodynamic parameters calculated from the adsorption data
      at different temperature showed that the adsorption reaction was endothermic and
      spontaneous. Low concentration of NaCl and foreign divalent cations hardly
      affected the adsorption. Negative effect of coexisting humic acid (HA) on CTC
      adsorption was also observed when the concentration of HA was lower than 20 mg L(
      1). But high concentration of HA (>20 mg L(-1)) increased the CTC adsorption on
      Fe(3)O(4) MNPs. The matrix effect of several environmental water samples on CTC
      adsorption was not evident. Fe(3)O(4) MNPs were regenerated by treatment with
      H(2)O(2) or calcination at 400 degrees C in N(2) atmosphere after separation from
      water solution by an external magnet. This research provided a high efficient and
      reusable adsorbent to remove CTC selectively from aqueous media.

PMID- 21724322
TI  - Efficient mineralization of dimethyl phthalate by catalytic ozonation using
      TiO2/Al2O3 catalyst.
AB  - The removal of dimethyl phthalate (DMP), which is a pollutant of concern in water
      environments, was carried out by catalytic ozonation with TiO(2)/Al(2)O(3)
      catalysts. The heterogeneous catalytic ozonation was an ozonation process
      combined with the catalytic and adsorptive properties of the TiO(2)/Al(2)O(3)
      catalysts to significantly accelerate the mineralization efficiency. Semi-batch
      ozonation was performed under various experimental conditions including the fed
      ozone concentration, catalyst type, catalyst dosage, and ultraviolet radiation on
      the degradation of DMP. The complete removal of DMP was efficiently achieved by
      both sole and catalytic ozonation; meanwhile, the presence of the catalysts
      slightly accelerated the elimination rate of DMP. On the other hand, the
      mineralization efficiency, in terms of total organic carbon (TOC) removal, was
      substantially enhanced by employing the TiO(2)/Al(2)O(3) catalyst. The
      mineralization efficiency using the TiO(2)/Al(2)O(3) catalyst was the highest,
      followed in decreasing order by the Al(2)O(3) catalyst, the TiO(2) catalyst, and
      sole ozonation. In addition, the use of the TiO(2)/Al(2)O(3) catalyst would
      increase the utilization efficiency of the fed ozone, especially in the late
      ozonation period. Furthermore, the decrease in the catalytic activity of the
      TiO(2)/Al(2)O(3) catalyst after multi-run experiments can be mostly recovered by
      an incineration process at a high temperature.

PMID- 21724323
TI  - Evaluation of physical stability and leachability of Portland pozzolona cement
      (PPC) solidified chemical sludge generated from textile wastewater treatment
      plants.
AB  - The chemical sludge generated from the treatment of textile dyeing wastewater is
      a hazardous waste as per Indian Hazardous Waste Management rules. In this paper,
      stabilization/solidification of chemical sludge was carried out to explore its
      reuse potential in the construction materials. Portland pozzolona cement (PPC)
      was selected as the binder system which is commercially available cement with 10
      25% fly ash interground in it. The stabilized/solidified blocks were evaluated in
      terms of unconfined compressive strength, block density and leaching of heavy
      metals. The compressive strength (3.62-33.62 MPa) and block density (1222.17
      1688.72 kg/m3) values as well as the negligible leaching of heavy metals from the
      stabilized/solidified blocks indicate that there is a potential of its use for
      structural and non-structural applications.

PMID- 21724324
TI  - Distribution, correlation and risk assessment of selected metals in urban soils
      from Islamabad, Pakistan.
AB  - Urban soil samples were analyzed for Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na,
      Pb, Sr and Zn by atomic absorption spectrophotometric method. Multivariate
      statistical approach was used to study the apportionment of selected metals in
      the soil samples during summer and winter. The degree of contamination along with
      the geoaccumulation index, enrichment factor and contamination factor was also
      evaluated. In water-extract of the soil samples, relatively higher levels were
      noted for Na, Ca, K, Fe, Mg, and Pb with average concentrations of 56.38, 33.82,
      12.53, 7.127, 5.994, and 1.045mg/kg during summer, while the mean metal levels
      during winter were 76.45, 38.05, 3.928, 0.627, 8.726, and 0.878mg/kg,
      respectively. In case of acid-extract of the soils, Ca, Fe, Mg, Na, K, Mn and Sr
      were found at 27,531, 12,784, 2769, 999.9, 737.9, 393.5, and 115.1mg/kg, during
      summer and 23,386, 3958, 3206, 254.6, 1511, 453.6, and 53.30mg/kg, during winter,
      respectively. Most of the metals showed random distribution with diverse
      correlations in both seasons. Principal component analysis and cluster analysis
      revealed significant anthropogenic intrusions of Cd, Pb, Co, Cr, Cu, Li, Zn and
      Na in the soils. Geoaccumulation indices and contamination factors indicated
      moderate to heavy contamination for Pb and Cd in the soils, while enrichment
      factor exhibited significant enrichment (EF>5) of Cd, Pb, Ca, Co, Li, Mn and Zn
      by anthropogenic activities. Overall, on the average basis, considerable degree
      of contamination (C(deg)>16) was observed in both seasons, although it was higher
      in winter. Present metal levels were also compared with those reported from other
      areas around the world.

PMID- 21724325
TI  - Acidic leaching both of zinc and iron from basic oxygen furnace sludge.
AB  - During the steel production in the basic oxygen furnace (BOF), approximately 7-15
      kg of dust per tonne of produced steel is generated. This dust contains
      approximately 1.4-3.2% Zn and 54-70% Fe. Regarding the zinc content, the BOF dust
      is considered to be highly problematic, and therefore new technological processes
      for recycling dusts and sludge from metallurgical production are still searched
      for. In this study the hydrometallurgical processing of BOF sludge in the
      sulphuric acid solutions under atmospheric pressure and temperatures up to 100 
      degrees C is investigated on laboratory scale. The influence of sulphuric acid
      concentration, temperature, time and liquid to solid ratio (L:S) on the leaching
      process was studied. The main aim of this study was to determine optimal
      conditions when the maximum amount of zinc passes into the solution whilst iron
      remains in a solid residue.

PMID- 21724326
TI  - A novel starch-based adsorbent for removing toxic Hg(II) and Pb(II) ions from
      aqueous solution.
AB  - A novel effective starch-based adsorbent was prepared through two common
      reactions, which included the esterification of starch with excess maleic
      anhydride in the presence of pyridine and the cross-linking reaction of the
      obtained macromonomer with acrylic acid by using potassium persulphate as
      initiator. The percentage of carboxylic groups of the macromonomer ranged from
      14% to 33.4%. The cross-linking degree of the adsorbent was tailored with the
      amount of acrylic acid which varied from 10wt% to 80wt%. Both Fourier transform
      infrared spectra and thermogravimetric analysis results verified the structure of
      the adsorbent. The maximum gel fraction and swelling ratio of the adsorbent were
      about 72% and 6.25, respectively, and they were able to be adjusted with the
      amount of monomers. The weight loss percentage of the adsorbent could reach 96.9%
      after immersing in the buffer solution that contained alpha-amylase for 14h. It
      was found that the adsorption capacities of the adsorbent for lead and mercury
      ions could be 123.2 and 131.2mg/g, respectively. In addition, the adsorbent was
      able to remove ca. 51-90% Pb(II) and Hg(II) ions that existed in the decoctions
      of four medicinal herbals.

PMID- 21724327
TI  - Nitrate removal from groundwater by cooperating heterotrophic with autotrophic
      denitrification in a biofilm-electrode reactor.
AB  - An intensified biofilm-electrode reactor (IBER) combining heterotrophic and
      autotrophic denitrification was developed for treatment of nitrate contaminated
      groundwater. The reactor was evaluated with synthetic groundwater (NO(3)(-)-N50
      mg L(-1)) under different hydraulic retention times (HRTs), carbon to nitrogen
      ratios (C/N) and electric currents (I). The experimental results demonstrate that
      high nitrate and nitrite removal efficiency (100%) were achieved at C/N = 1, HRT
      = 8h, and I = 10 mA. C/N ratios were reduced from 1 to 0.5 and the applied
      electric current was changed from 10 to 100 mA, showing that the optimum running
      condition was C/N = 0.75 and I = 40 mA, under which over 97% of NO(3)(-)-N was
      removed and organic carbon (methanol) was completely consumed in treated water.
      Simultaneously, the denitrification mechanism in this system was analyzed through
      pH variation in effluent. The CO(2) produced from the anode acted as a good pH
      buffer, automatically controlling pH in the reaction zone. The intensified
      biofilm-electrode reactor developed in the study was effective for the treatment
      of groundwater polluted by nitrate.

PMID- 21724328
TI  - Enantiomer-specific toxicity and bioaccumulation of alpha-cypermethrin to
      earthworm Eisenia fetida.
AB  - Alpha-cypermethrin, a synthetic pyrethroid, is highly effective against a wide
      range of chewing and sucking insects in crops, and it is a racemic mixture of two
      enantiomers ((+)-1R-cis-alphaS+(-)-1S-cis-alphaR). Studies about the toxicity of
      alpha-cypermethrin to non-target organisms are mainly focused on aquatic
      organisms, whereas information regarding terrestrial organisms is relatively much
      less. Very little report about its enantioselective toxicity is known, so the
      present study tested the enantiomer-specific acute toxicity to earthworm Eisenia
      fetida. Experiment about bioaccumulation of two enantiomers in soil was
      conducted, peak-shaped accumulation curves were observed for both enantiomers,
      and the calculated biota to soil accumulations factor (BSAF) have significant
      difference between the two enantiomers. It was obvious that earthworm can uptake
      alpha-cypermethrin enantioselectively, preferentially accumulating (-)-(1S-cis
      alphaR)-enantiomer. Great difference in toxicity to earthworm between two
      enantiomers was found, and the calculated LC(50) values for (+)-(1R-cis-alphaS)-,
      (-)-(1S-cis-alphaR)-, and rac-alpha-cypermethrin were 49.53, 1663.87 and 165.61
      ng/cm(2), respectively. The acute toxicity of alpha-cypermethrin enantiomers was
      enantioselective.

PMID- 21724329
TI  - Adsorption of Reactive Red M-2BE dye from water solutions by multi-walled carbon
      nanotubes and activated carbon.
AB  - Multi-walled carbon nanotubes and powdered activated carbon were used as
      adsorbents for the successful removal of Reactive Red M-2BE textile dye from
      aqueous solutions. The adsorbents were characterised by infrared spectroscopy,
      N(2) adsorption/desorption isotherms and scanning electron microscopy. The
      effects of pH, shaking time and temperature on adsorption capacity were studied.
      In the acidic pH region (pH 2.0), the adsorption of the dye was favourable using
      both adsorbents. The contact time to obtain equilibrium at 298K was fixed at 1h
      for both adsorbents. The activation energy of the adsorption process was
      evaluated from 298 to 323K for both adsorbents. The Avrami fractional-order
      kinetic model provided the best fit to the experimental data compared with pseudo
      first-order or pseudo-second-order kinetic adsorption models. For Reactive Red M
      2BE dye, the equilibrium data were best fitted to the Liu isotherm model.
      Simulated dyehouse effluents were used to check the applicability of the proposed
      adsorbents for effluent treatment.

PMID- 21724330
TI  - Environmental impact of industrial sludge stabilization/solidification products:
      chemical or ecotoxicological hazard evaluation?
AB  - Nowadays, the classification of industrial solid wastes is not based on risk
      analysis, thus the aim of this study was to compare the toxicity classifications
      based on the chemical and ecotoxicological characterization of four industrial
      sludges submitted to a two-step stabilization/solidification (S/S) processes. To
      classify S/S products as hazardous or non-hazardous, values cited in Brazilian
      chemical waste regulations were adopted and compared to the results obtained with
      a battery of biotests (bacteria, alga and daphnids) which were carried out with
      soluble and leaching fractions. In some cases the hazardous potential of
      industrial sludge was underestimated, since the S/S products obtained from the
      metal-mechanics and automotive sludges were chemically classified as non
      hazardous (but non-inert) when the ecotoxicity tests showed toxicity values for
      leaching and soluble fractions. In other cases, the environmental impact was
      overestimated, since the S/S products of the textile sludges were chemically
      classified as non-inert (but non-hazardous) while ecotoxicity tests did not
      reveal any effects on bacteria, daphnids and algae. From the results of the
      chemical and ecotoxicological analyses we concluded that: (i) current regulations
      related to solid waste classification based on leachability and solubility tests
      do not ensure reliable results with respect to environmental protection; (ii) the
      two-step process was very effective in terms of metal immobilization, even at
      higher metal-concentrations. Considering that S/S products will be subject to
      environmental conditions, it is of great interest to test the ecotoxicity
      potential of the contaminants release from these products with a view to avoiding
      environmental impact given the unreliability of ecotoxicological estimations
      originating from chemical analysis.

PMID- 21724332
TI  - Occurrence of filaria in domestic dogs of Samburu pastoralists in Northern Kenya
      and its associations with canine distemper.
AB  - Samples of blood (serum, smears and blood preserved with ethanol) were collected
      from dogs during a vaccination campaign in northern Kenya in the years 2006 and
      2007. Blood was screened for filarial parasites using molecular and microscopy
      methods and sera were tested for antibodies against canine distemper virus (CDV).
      Parasitological examination revealed the presence of two species of canine
      filariae: Acanthocheilonema dracunculoides and A. reconditum. The DNA from the
      former species was detected in 58% dogs sampled in 2006 and 36% dogs sampled in
      2007, whereas the latter was found only in 4.2% samples collected in 2007.
      Microfilariae were found in 33.8% blood smears collected in 2006 and 10.6% blood
      smears collected in 2007. The seroprevalence of CDV was 33.4% in 2006 and 11.2%
      in 2007. The effect of sex, age and CDV-seropositivity/seronegativity on the
      occurrence of A. dracunculoides was evaluated. Infection by A. dracunculoides was
      more common in males and in dogs with a positive antibody titer for canine
      distemper, but evenly distributed among different age groups. The difference in
      the prevalence of A. dracunculoides in two isolated mountain ranges was not
      statistically significant. Methodologies available for detection and
      determination of canine filariae are compared, underlining methodical pitfalls
      arising through the determination of less common filarial species. The role of
      single epidemiological factors and possible association between canine distemper
      and filariasis are discussed.

PMID- 21724333
TI  - Validation of the Zurich burn-biofilm model.
AB  - BACKGROUND: Despite advances in the use of topical and parenteral antimicrobial
      therapy and the practice of early tangential burn-wound excision, bacterial
      infection remains a major problem in the management of burn victims today. The
      purpose of this study was to design and evaluate a polyspecies biofilm model with
      bacteria known to cause severe infections in burn patients. The model is simple
      to prepare, maintain and analyse, and allows for short-term exposure to
      antimicrobials. RESULTS: Initial experiments showed that it was impossible to
      establish balanced polyspecies biofilms with an inoculum of Gram-positive and 
      negative bacteria. After 64.5 h of incubation, the Gram-negative bacteria
      (Escherichia coli and Pseudomonas aeruginosa) had suppressed the Gram-positives
      (Enterococcus faecalis, Staphylococcus aureus and Streptococcus intermedius).
      However, adding the Gram-negative bacteria after 41.5 h to an established biofilm
      of Gram-positives resulted in a balanced microbial consortium. After 64.5 h, all
      species were present in high numbers (10(7) to 10(8) colony forming units (CFU)
      per biofilm). Multiple repetitions showed high reproducibility of biofilm
      formation without significant differences between and within experiments.
      Combined fluorescence in situ hybridisation/confocal laser scanning microscopy
      (FISH/CLSM) analyses, for which biofilms had to be grown on a different non
      flexible substrate (hydroxy apatite), revealed that, by 41.5 h, the biofilm
      consisted of an almost confluent layer of bacteria firmly adherent to the
      substratum. After 64.5 h (22 h after the addition of the Gram negatives), the
      biofilm consisted of a confluent mixture of single cells, an abundance of
      galaxies of bacteria with small lacunae and large amounts of extracellular matrix
      polysaccharides. CONCLUSIONS: The polyspecies biofilm model contains the most
      prevalent burn-associated Gram-positive and Gram-negative bacterial pathogens and
      mimics the Gram-negative shift observed in vivo. It shows excellent
      reproducibility. It should allow adaptation to the bacterial spectrum prevalent
      in different burn centres and lead to a much more reliable investigation of the
      efficiency of topical antimicrobial agents than models operating with planktonic
      bacteria. The experiments further open up the perspective to create an in vivo
      model using these biofilms as infectious agents.

PMID- 21724334
TI  - Quality of life after burns in childhood (5-15 years): children experience
      substantial problems.
AB  - The aim of our study was to assess prevalence and correlates related to sub
      optimal outcome after pediatric burns and to make a comparison with pediatric
      injuries not related to burns. We conducted a cross-sectional study on quality of
      life (QOL) after burns in a sample (n=138; median 24 months post-burn) of Dutch
      and Flemish children (5-15 years) with an admission to a burn center. QOL was
      assessed with the Burn Outcomes Questionnaire (BOQ). The generic EuroQol-5D was
      used to allow for a comparison with children after injuries not related to burns.
      More than half of the children had long-term limitations. According to the BOQ,
      children frequently (>50%) experienced sub optimal functioning on 5 out of 12
      dimensions, concerning 'appearance', 'parental concern', 'itch', 'emotional
      health' and 'satisfaction with current state'. Children with a high total burned
      surface area (TBSA >=10%) showed significantly more sub optimal functioning on
      'upper extremity function' (OR=5.3; >=20% TBSA), 'appearance' (OR=5.5; >=10-20%
      TBSA), 'satisfaction with current state' (OR=3.4; >=10-20% TBSA) and 'parental
      concern' (OR=3.4; >=10-20% TBSA), compared to children with less than 10% TBSA.
      Burn victims at 9 months post-injury appeared to be worse off at several health
      dimensions. After 24 months generic quality of life of in pediatric burns was
      more comparable to pediatric injuries not related to burns. Children after burns
      experience substantial problems, mainly on itch and appearance and several
      psychosocial dimensions. More extensive burns are related to sub optimal
      functioning. These problems are in part specific for burns and not picked up by
      generic measures.

PMID- 21724335
TI  - Stress response and humoral immune system alterations related to chronic
      hypergravity in mice.
AB  - Spaceflights are known to induce stress and immune dysregulation. Centrifugation,
      as hindlimb unloading, is a good ground based-model to simulate altered gravity
      which occurs during space missions. The aim of this study was to investigate the
      consequences of a long-term exposure to different levels of hypergravity on the
      stress response and the humoral immunity in a mouse model. For this purpose,
      adult C57Bl/6J male mice were subjected for 21 days either to control conditions
      or to 2G or 3G acceleration gravity forces. Corticosterone level and anxiety
      behavior revealed a stress response which was associated with a decrease of body
      weight, after 21-day of centrifugation at 3G but not at 2G. Spleen lymphocyte
      lipopolysaccharide (LPS) responsiveness was diminished by 40% in the 2G group
      only, whereas a decrease was noted when cells were stimulated with concanavalin A
      for both 2G and 3G groups (about 25% and 20%, respectively) compared to controls.
      Pro-inflammatory chemokines (MCP-1 and IP-10) and Th1 cytokines (IFNgamma and
      IL2) were slightly decreased in the 2G group and strongly decreased in the 3G
      mouse group. Regarding Th2 cytokines (IL4, IL5) no further significant
      modification was observed, whereas the immunosuppressive cytokine IL10 was
      slightly increased in the 3G mice. Finally, serum IgG concentration was twice
      higher whereas IgA concentration was slightly increased (about 30%) and IgM were
      unchanged in 2G mice compared to controls. No difference was observed in the 3G
      group with these isotypes. Consequently, functional immune dysregulations and
      stress responses were dependent of the gravity level.

PMID- 21724336
TI  - The Steroid/Peptide Theory of Social Bonds: integrating testosterone and peptide
      responses for classifying social behavioral contexts.
AB  - Hormones, and hormone responses to social contexts, are the proximate mechanisms
      of evolutionary pathways to pair bonds and other social bonds. Testosterone (T)
      is implicated in tradeoffs relevant to pair bonding, and oxytocin (OT) and
      arginine vasopressin (AVP) are positively tied to social bonding in a variety of
      species. Here, we present the Steroid/Peptide Theory of Social Bonds (S/P
      Theory), which integrates T and peptides to provide a model, set of predictions,
      and classification system for social behavioral contexts related to social bonds.
      The S/P Theory also resolves several paradoxes apparent in the literature on
      social bonds and hormones: the Offspring Defense Paradox, Aggression Paradox, and
      Intimacy Paradox. In the S/P Theory, we partition aggression into antagonistic
      and protective aggression, which both increase T but exert distinct effects on
      AVP and thus social bonds. Similarly, we partition intimacy into sexual and
      nurturant intimacy, both of which increase OT and facilitate social bonds, but
      exert distinct effects on T. We describe the utility of the S/P Theory for
      classifying 'tricky' behavioral contexts on the basis of their hormonal responses
      using partner cuddling, a behavior which is assumed to be nurturant but increases
      T, as a test case of the S/P Theory. The S/P Theory provides a comparative basis
      for conceptualizing and testing evolved hormonal pathways to pair bonds with
      attention to species, context, and gender/sex specificities and convergences.

PMID- 21724337
TI  - Role of leptin in human visceral leishmaniasis?
AB  - Human visceral leishmaniasis (VL) is frequently found in poor population who are
      suffering from malnutrition in endemic areas. Therefore, obviously they may have
      reduced levels of leptin due to reduction in number of adipocytes which are major
      source of leptin production. Human pathogenesis of VL and reduced levels of
      leptin both are associated with increase in Th2 type immune response,
      characterized by secretion of cytokines such as IL-4 and IL-10. Whereas, the
      protective immune response during visceral leishmaniasis is associated with
      effective Th1 type immune response characterized by secretion of IFN-gamma, IL-2
      and IL-12, which correlates with leptin induction of T cells polarizing to Th1
      population and secretion of proinflammatory cytokines, and also inhibition of Th2
      type response. Therefore, we hypothesized that leptin might be effective in
      treatment of visceral leishmaniasis alone or VL patients who have co-infection
      with other immune deficiency syndromes such as AIDS/diabetes/autoimmune disorders
      by regulation of Th1/Th2 homeostasis.

PMID- 21724338
TI  - The Cannabis Withdrawal Scale development: patterns and predictors of cannabis
      withdrawal and distress.
AB  - BACKGROUND: Rates of treatment seeking for cannabis are increasing, and relapse
      is common. Management of cannabis withdrawal is an important intervention point.
      No psychometrically sound measure for cannabis withdrawal exists, and as a result
      treatment developments cannot be optimally targeted. The aim is to develop and
      test the psychometrics of the Cannabis Withdrawal Scale and use it to explore
      predictors of cannabis withdrawal. METHODS: A volunteer sample of 49 dependent
      cannabis users provided daily scores on the Cannabis Withdrawal Scale during a
      baseline week and 2 weeks of abstinence. RESULTS: Internal reliability
      (Cronbach's alpha=0.91), test-retest stability (average intra-class
      correlation=0.95) and content validity analysis show that the Cannabis Withdrawal
      Scale has excellent psychometric properties. Nightmares and/or strange dreams was
      the most valid item (Wald chi2=105.6, P<0.0001), but caused relatively little
      associated distress (Wald chi2=25.11, P=0.03). Angry outbursts were considered
      intense (Wald chi2=73.69, P<0.0001) and caused much associated distress (Wald
      chi2=45.54, P<0.0001). Trouble getting to sleep was also an intense withdrawal
      symptom (Wald chi2=42.31, P<0.0001) and caused significant associated distress
      (Wald chi2=47.76, P<0.0001). Scores on the Severity of Dependence Scale predicted
      cannabis withdrawal. CONCLUSIONS: The Cannabis Withdrawal Scale can be used as a
      diagnostic instrument in clinical and research settings where regular monitoring
      of withdrawal symptoms is required.

PMID- 21724339
TI  - Chronic hepatitis C virus infection and increases in viral load in a prospective
      cohort of young, HIV-uninfected injection drug users.
AB  - BACKGROUND: Chronic hepatitis C (HCV) infection, defined as persistent RNA (viral
      load) for at least 6 months, accounts for up to 50% of all cirrhosis, end-stage
      liver disease and liver cancer cases. Moreover, elevated HCV viral load is
      consistently associated with high infectivity and poor therapy response. This
      study aims to identify modifiable behavioral correlates both chronic HCV
      infection and increases in viral load over time among injection drug users
      (IDUs). METHODS: Cross-sectional and longitudinal analyses were performed using
      self-interview and serological data from a prospective cohort study (2002-2006)
      among young (age 18-35), HIV-negative, HCV therapy-naive IDUs (n=113) from
      metropolitan Chicago, Illinois, USA. RESULTS: After adjustment for age, gender
      and race/ethnicity, using drugs measured or mixed in someone else's syringe (odds
      ratio=2.7, 95% confidence interval: 1.1, 6.7) was associated with chronic (n=75,
      66%) versus resolved (n=38, 34%) HCV infection status. Among chronically-infected
      IDUs, injecting with a new, sterile syringe infrequently (<1/2 half the time when
      injecting) compared to frequently (1/2 the time or more when injecting) was
      associated with increases in viral load over time after adjusting for age,
      gender, race/ethnicity and time effects. CONCLUSIONS: Reductions in risky
      injection-related practices among young IDUs may ameliorate both the burden of
      chronic HCV infection-related liver disease and elevated viral load-related poor
      treatment response.

PMID- 21724340
TI  - Integrating field methodology and web-based data collection to assess the
      reliability of the Alcohol Use Disorders Identification Test (AUDIT).
AB  - Field methodologies offer a unique opportunity to collect ecologically valid data
      on alcohol use and its associated problems within natural drinking environments.
      However, limitations in follow-up data collection methods have left unanswered
      questions regarding the psychometric properties of field-based measures. The aim
      of the current study is to evaluate the reliability of self-report data collected
      in a naturally occurring environment - as indexed by the Alcohol Use Disorders
      Identification Test (AUDIT) - compared to self-report data obtained through an
      innovative web-based follow-up procedure. Individuals recruited outside of bars
      (N=170; mean age=21; range 18-32) provided a BAC sample and completed a self
      administered survey packet that included the AUDIT. BAC feedback was provided
      anonymously through a dedicated web page. Upon sign in, follow-up participants
      (n=89; 52%) were again asked to complete the AUDIT before receiving their BAC
      feedback. Reliability analyses demonstrated that AUDIT scores - both continuous
      and dichotomized at the standard cut-point - were stable across field- and web
      based administrations. These results suggest that self-report data obtained from
      acutely intoxicated individuals in naturally occurring environments are reliable
      when compared to web-based data obtained after a brief follow-up interval.
      Furthermore, the results demonstrate the feasibility, utility, and potential of
      integrating field methods and web-based data collection procedures.

PMID- 21724342
TI  - Experimental cowpox virus infection in rats.
AB  - A pet rat derived cowpox virus strain, which was also the source of human
      infections, was used to infect young Wistar and fancy rats. After an incubation
      period of 6 days the animals developed a severe, often fatal disease with high
      amounts of virus detected in oropharyngeal secretions.

PMID- 21724341
TI  - Marijuana use and tobacco smoking cessation among heavy alcohol drinkers.
AB  - BACKGROUND: Whereas problem drinking impedes smoking cessation, less is known
      whether marijuana use affects smoking cessation outcomes and whether smoking
      cessation treatment leads to changes in marijuana smoking. METHODS: In a
      randomized clinical trial that recruited 236 heavy drinkers seeking smoking
      cessation treatment, we examined whether current marijuana smokers (n=57)
      differed from the rest of the sample in tobacco smoking and alcohol use outcomes
      and whether the patterns of marijuana use changed during treatment. RESULTS: Half
      of the marijuana users reported smoking marijuana at least weekly (an average of
      42% of possible smoking days), the other half used infrequently, an average of 5%
      of possible days. There were no significant differences between the marijuana use
      groups and non-users on smoking outcomes and marijuana use did not predict
      smoking lapses. All participants made large reductions in weekly alcohol
      consumption during the trial, with weekly marijuana users reducing their drinking
      by 47% and at a faster rate than non-marijuana users after the 8-week follow-up.
      Weekly marijuana smokers also steadily decreased their marijuana use over the
      course of the study (at 8-, 16-, and 26-week follow-ups) by more than 24%.
      CONCLUSIONS: These data suggest that frequent marijuana smokers may benefit from
      smoking cessation interventions, even when marijuana use is not explicitly
      discussed. These individuals do not show any more difficulty than other cigarette
      smokers in making efforts to reduce tobacco smoking and in fact, make meaningful
      changes in marijuana use and heavy drinking. Future clinical trials should
      examine whether smoking cessation treatment that addresses both marijuana and
      tobacco smoking leads to substantial reductions in marijuana use.

PMID- 21724343
TI  - Comparative analysis on mRNA expression level and methylation status of DAZL gene
      between cattle-yaks and their parents.
AB  - The autosomal gene Deleted in Azoospermia Like (DAZL) is essential for
      spermatogenesis. The absence of DAZL gene will lead to meiotic arrest,
      spermatogenetic failure and male infertility, and so it was usually considered as
      a candidate gene for male infertility in cattle-yaks. To study the regulatory
      mechanism of DAZL expression in cattle-yaks, DAZL mRNA expression and DAZL gene
      methylation patterns in testes of cattle, yaks and cattle-yaks were examined
      using real-time PCR and bisulfite sequencing. The results showed that DAZL mRNA
      expression in testes of cattle-yaks was lower than that in cattle and yak (about
      1/2-1/3 of cattle and yak). The methylation level of DAZL in cattle-yaks (85.6%)
      was significantly higher than that in cattle (69.8%) and yaks (71.4%) (P<0.01).
      The methylation and mRNA expression level of DAZL was significantly negatively
      correlated in the testes of cattle-yaks and their parents (P<0.01). We propose
      that the methylation of DAZL gene plays an important role in DAZL transcriptional
      regulation and maybe have a severe effect on spermatogenesis and male sterility
      in cattle-yaks.

PMID- 21724344
TI  - Long-term adherence to the Mediterranean diet reduces the prevalence of
      hyperuricaemia in elderly individuals, without known cardiovascular disease: the
      Ikaria study.
AB  - BACKGROUND: The purpose of this study was to evaluate the impact of adherence to
      Mediterranean diet on serum uric acid (UA) levels in elderly individuals, without
      known cardiovascular disease. METHODS: During 2009, 281 females (75+/-6 years
      old) and 257 males (75+/-7 years old) permanent inhabitants of the island, were
      voluntarily enrolled. A diet score that assesses the inherent characteristics of
      the Mediterranean diet (MedDietScore, range 0-55) was applied. Serum levels of UA
      were determined using an enzymatic colorimetric test through the uricase
      peroxidase method. Hyperuricaemia was defined as UA>7 mg/dL in males and 6 mg/dL
      in females. RESULTS: Prevalence of hyperuricaemia was 34% in males and 25% in
      females (p=0.02). Mean level of adherence to the Mediterranean diet was 35+/-2.
      Linear regression analysis revealed that MedDietScore was inversely associated
      with UA levels (b+/-SE: -1.48+/-0.17, p<0.001) in the overall sample, after
      controlling for hypertension, hypercholesterolemia, diabetes mellitus, creatinine
      clearance, physical activity, and coffee consumption. When the analysis was
      stratified by gender, MedDietScore was inversely associated with UA levels in
      males (b+/-SE: -1.10+/-0.42, p=0.009), but not in females (b+/-SE: 0.04+/-0.41,
      p=0.92). CONCLUSION: Another cardioprotective effect of Mediterranean diet was
      revealed, through the modification of UA levels in elderly individuals. The
      potential different effect size as regards the relationship between diet and UA
      levels between genders, deserves further investigation.

PMID- 21724345
TI  - Mixed effects modelling for glass category estimation from glass refractive
      indices.
AB  - 520 Glass fragments were taken from 105 glass items. Each item was either a
      container, a window, or glass from an automobile. Each of these three classes of
      use are defined as glass categories. Refractive indexes were measured both
      before, and after a programme of re-annealing. Because the refractive index of
      each fragment could not in itself be observed before and after re-annealing, a
      model based approach was used to estimate the change in refractive index for each
      glass category. It was found that less complex estimation methods would be
      equivalent to the full model, and were subsequently used. The change in
      refractive index was then used to calculate a measure of the evidential value for
      each item belonging to each glass category. The distributions of refractive index
      change were considered for each glass category, and it was found that, possibly
      due to small samples, members of the normal family would not adequately model the
      refractive index changes within two of the use types considered here. Two
      alternative approaches to modelling the change in refractive index were used, one
      employed more established kernel density estimates, the other a newer approach
      called log-concave estimation. Either method when applied to the change in
      refractive index was found to give good estimates of glass category, however, on
      all performance metrics kernel density estimates were found to be slightly better
      than log-concave estimates, although the estimates from log-concave estimation
      prossessed properties which had some qualitative appeal not encapsulated in the
      selected measures of performance. These results and implications of these two
      methods of estimating probability densities for glass refractive indexes are
      discussed.

PMID- 21724346
TI  - [Factors associated with the lack of proposition for HIV-AIDS and hepatitis B and
      C screening to underprivileged immigrants].
AB  - BACKGROUND: Underprivileged immigrants from endemic areas cumulate risk factors
      for infections by HIV-AIDS and hepatitis B and C. Free primary care consultations
      are available to them in the four health centers of the city of Paris. The
      objective of our study was to identify socio-demographic and medical factors
      related to the lack of screening proposition for HIV-AIDS and hepatitis B and C
      to new immigrant patients in these centers in 2003. METHODS: For each disease,
      the absence of screening proposition was analyzed according to geographical
      origin, length of stay in France, type of accommodation, type of health insurance
      and symptom motivating the encounter in logistic mixed models adjusted on sex and
      age. RESULTS: About 500 patients were included in the analysis. Three-quarters of
      them were male and from Sub-Saharan Africa. They were 36years old on average.
      Half of them lived in shelters for homeless or immigrants. Their median stay
      lasted two years. They rarely came for screening (1%), sometimes for asthenia
      (6%) and two-thirds of them for uro-genito-digestive signs. The results were
      similar for the three screenings. The lack of screening proposition was about 45%
      and varied significantly between physicians. Factors significantly associated
      with the lack of screening proposition were: coming from non-Sub-Saharan Africa
      (especially from North Africa and Middle East; OR=1.7 to 3.6) and having a health
      insurance (OR=2.4 to 2.6) regardless of the disease; being a female (OR=2.0 to
      2.3) in the case of hepatitis; and having a length of stay in France greater than
      or equal to five years (OR=1.9) for hepatitis B. CONCLUSIONS: Our results should
      encourage practitioners to provide more screening to underprivileged immigrants
      and draws attention to immigrants from non-Sub-Saharan origin and those with
      health insurance. Factors that might explain doctor and gender-related
      variability observed in hepatitis are highlighted.

PMID- 21724347
TI  - Association of platelet-SDF-1 with hemodynamic function and infarct size using
      cardiac MR in patients with AMI.
AB  - PURPOSE: Platelet-derived stromal-cell-derived factor-1 (SDF-1) plays an
      important role in trafficking hematopoetic progenitor cells for tissue
      regeneration and neovascularisation. The aim was to evaluate platelet-SDF-1 and
      CD34(+) progenitor cells in patients with acute myocardial infarction (AMI)
      compared with hemodynamic function and infarct size using late gadolinium
      enhancement (LGE) cardiac magnetic resonance (CMR) imaging. MATERIALS AND
      METHODS: We consecutively evaluated 40 patients with AMI, who received coronary
      angiography for primary coronary intervention. Blood was sampled for flow
      cytometry to determine mean fluorescence intensity (MFI) of platelet-SDF-1 and
      for isolation of CD34(+) progenitor cells. 48h and three months after coronary
      stenting, all patients underwent 1.5T CMR for volumetric assessment and LGE.
      RESULTS: Patients with enhanced platelet-SDF-1 expression (median>=68.5MFI)
      showed a significant amelioration of left ventricular ejection fraction (LVEF)
      (baseline vs. follow-up mean+/-SD: 45+/-6% vs. 56+/-6%; P=0.018) and of stroke
      volume (73.1+/-19.1mL vs. 89.9+/-21.3mL; P=0.032) at three-month follow-up in
      contrast to patients with a decreased platelet-SDF-1 expression level (LVEF: 53+/
      8% vs. 56+/-10%; P=0.267; stroke volume: 85.6+/-23.1mL vs. 87.4+/-23.2mL;
      P=0.803). Inversely, LGE infarct size showed significantly reduced in patients
      with enhanced platelet-SDF-1 expression at three months (18.9+/-12mL vs. 6.3+/
      5.1mL; P=0.002) compared to patients with decreased platelet-SDF-1 (12.7+/-12.7mL
      vs. 7.6+/-8.4mL; P=0.156). Time-dependent autocorrelation coefficients shifted
      for both SV (lag 1: r=-0.368; P=0.001) and the number of CD34(+) cells (lag 1:
      r=0.633; P=0.001) to a positive autocorrelation (SV; lag 2: r=0.295; P=0.001;
      CD34(+) cells; lag 2: r=0.287; P=0.001). Patients with increased number of
      CD34(+) cells (median>=420cells/hpf) showed a significant amelioration of stroke
      volume in three-month follow-up (83.9+/-5.3mL vs. 99.4+/-4.1mL; P=0.020) compared
      with patients with decreased number of CD34(+) cells (69.3+/-4.1mL vs. 76.1+/
      3.2mL; P=0.282). CONCLUSIONS: Platelet-SDF-1 and number of CD34(+) progenitor
      cells are associated with CMR hemodynamic function in patients with AMI.

PMID- 21724348
TI  - Flow and peak velocity measurements in patients with aortic valve stenosis using
      phase contrast MR accelerated with k-t BLAST.
AB  - OBJECTIVE: To investigate the accuracy of velocity measurements in patients with
      aortic valve stenosis using phase contrast (PC) imaging accelerated with SENSE
      (Sensitivity Encoding) and k-t BLAST (Broad-use Linear Acquisition Speed-up
      Technique). METHODS: Accelerated quantitative breath hold PC measurements, using
      SENSE and k-t BLAST, were performed in twelve patients whose aortic valve
      stenosis had been initially diagnosed using echocardiography. Stroke volume (SV)
      and peak velocity measurements were performed on each subject in three adjacent
      slices using both accelerating methods. RESULTS: The peak velocities measured
      with PC MRI using SENSE were -8.0+/-9.5% lower (p<0.01) compared to the peak
      velocities measured with k-t BLAST and the correlation was r=0.83. The stroke
      volumes when using SENSE were slightly higher 0.4+/-17.1 ml compared to the SV
      obtained using k-t BLAST but the difference was not significant (p>0.05).
      CONCLUSIONS: In this study higher peak velocities were measured in patients with
      aortic stenosis when combining k-t BLAST with PC MRI compared to PC MRI using
      SENSE. A probable explanation of this difference is the higher temporal
      resolution achieved in the k-t BLAST measurement. There was, however, no
      significant difference between calculated SV based on PC MRI using SENSE and k-t
      BLAST, respectively.

PMID- 21724349
TI  - Accurate perioperative flow measurement of the portal vein and hepatic and renal
      artery: a role for preoperative MRI?
AB  - BACKGROUND: Quantification of abdominal blood flow is essential for a variety of
      gastrointestinal and hepatic topics such as liver transplantation or metabolic
      flux measurement, but those need to be performed during surgery. It is not clear
      whether Duplex Doppler Ultrasound during surgery or MRI before surgery is the
      tool to choose. OBJECTIVE: To examine whether preoperative evaluation of
      abdominal blood flow using MRI could prove to be a useful and reliable
      alternative for the perioperative sonographic approach. METHODS: In this study
      portal and renal venous flow and hepatic arterial flow were sequentially
      quantified by preoperative MRI, preoperative and perioperative Duplex Doppler
      Ultrasound (DDUS). 55 Patients scheduled for major abdominal surgery were studied
      and methods and settings were compared. Additionally, average patient population
      values were compared. RESULTS: Mean (+/-SD) plasmaflow measured by perioperative
      DDUS, preoperative DDUS and MRI, respectively was 433+/-200/423+/-162/507+/-96
      ml/min (portal vein); 96+/-70/74+/-41/108+/-91 ml/min (hepatic artery); 248+/
      139/201+/-118/219+/-69 ml/min (renal vein). No differences between the different
      settings of DDUS measurement were detected. Equality of mean was observed for all
      measurements. Bland Altman Plots showed widespread margins. Hepatic arterial flow
      measurements correlated with each other, but portal and renal venous flow
      correlations were absent. CONCLUSIONS: Surgery and method (DDUS vs. MRI) do not
      affect mean flow values. Individual comparison is restricted due to wide range in
      measurements. Since MRI proves to be more reliable with respect to inter-observer
      variability, we recommend using mean MRI results in experimental setups.

PMID- 21724350
TI  - Thyroid size change by CT monitoring after sorafenib or sunitinib treatment in
      patients with renal cell carcinoma: comparison with thyroid function.
AB  - OBJECTIVE: Hypothyroidism is a common complication in patients receiving tyrosine
      kinase inhibitors. We evaluated the relationship between thyroid size evident on
      CT and thyroid function in patients with advanced renal cell carcinoma (RCC)
      receiving tyrosine kinase inhibitors. MATERIALS AND METHODS: Forty-two patients
      with metastatic RCC receiving tyrosine kinase inhibitors (sorafenib n=25;
      sunitinib n=17) and, followed-up for >=12 months were eligible. Patients who had
      ever shown an elevated thyroid-stimulating hormone (TSH) level of >10 mU/l were
      defined as having "hypothyroidism". CT scans were performed before, and 3, 6, 9,
      and 12 months after the start of treatment. The area of the thyroid in the
      maximum section at each examination was measured and compared with that before
      treatment. Using repeated-measures ANOVA, differences in thyroid size were
      compared over time between patients with and without "hypothyroidism", in
      relation to the type of drug employed. RESULTS: Twenty-one patients (sorafenib 9,
      sunitinib 12) developed "hypothyroidism" 95+/-88 days (range 12-315 days) after
      the start of treatment. In such patients, the thyroid was reduced in size to 89+/
      16% after 3 months, 81+/-21% after 6 months, 71+/-21% after 9 months and 68+/-21%
      after 12 months, whereas the patients without "hypothyroidism" maintained a
      thyroid size of 90+/-12% even after 12 months (p=0.0030). Among the patients with
      "hypothyroidism", those treated with sunitinib tended to show greater thyroid
      size reduction than those with sorafenib (59+/-23% vs. 79+/-13%, after 12
      months). CONCLUSION: Tyrosine kinase inhibitors cause an apparent thyroid size
      reduction in patients with "hypothyroidism".

PMID- 21724351
TI  - Insertion of central venous catheters for hemodialysis using angiographic
      techniques in patients with previous multiple catheterizations.
AB  - INTRODUCTION: Central venous catheter placement is an effective alternative
      vascular access for dialysis in patients with chronic renal failure. The purpose
      of this study was to evaluate the insertion of central venous catheters for
      hemodialysis using angiographic techniques in patients with previous multiple
      catheterizations in terms of efficacy of the procedure and early complications.
      MATERIALS AND METHODS: Between 2008 and 2010, the vascular access team of our
      hospital placed 409 central venous catheters in patients with chronic renal
      failure. The procedure was performed using the Seldinger blind technique. In 18
      (4.4%) cases it was impossible to advance the guidewire, and so the patients were
      transported to the angiography suite. RESULTS: Using the angiographic technique,
      the guidewire was advanced in order to position the central venous catheter. The
      latter was inserted into the subclavian vein in 12 (66.6%) cases, into the
      internal jugular vein in 4 (22.2%) and into the femoral vein in 2 (11.1%) cases.
      There was only one complicated case with severe arrhythmia in 1 (5.5%) patient.
      CONCLUSION: Our results suggest that insertion of central venous catheters using
      angiographic techniques in hemodialysis patients with previous multiple
      catheterizations is a safe and effective procedure with few complications and
      high success rates.

PMID- 21724352
TI  - Assessment of coronary artery disease by post-mortem cardiac MR.
AB  - OBJECTIVES: Minimally invasive or virtual autopsies are being advocated as
      alternative to traditional autopsy, but have limited abilities to detect coronary
      artery disease. It was the objective of this study to assess if the occurrence of
      chemical shift artifacts (CSA) along the coronary arteries on non-contrast, post
      mortem cardiac MR may be used to investigate coronary artery disease. METHODS: We
      retrospectively compared autopsy and CT findings of 30 cases with significant
      (>=75%), insignificant (<75%), or absent coronary artery stenosis to post-mortem
      cardiac MR findings. The chi-square test was used to investigate if the
      occurrence of CSA depends on the presence or absence of stenosis. Sensitivity,
      specificity and predictive values were calculated for each finding. RESULTS: CSA
      indicates the absence of (significant) stenosis (p<0.001). The occurrence of
      paired dark bands in lieu of CSA on post-mortem cardiac MR suggests (significant)
      coronary arteries stenosis (p<0.001). Both findings have a high specificity but
      low sensitivity. CONCLUSIONS: CSA is a marker of vessel patency. The presence of
      paired dark bands indicates stenosis. These criteria improve the ability of
      minimally invasive or virtual autopsy to detect coronary artery disease related
      deaths.

PMID- 21724353
TI  - Coronary CT angiography: how should physicians use it wisely and when do
      physicians request it appropriately?
AB  - Coronary CT angiography has been increasingly used in the diagnosis of coronary
      artery disease due to rapid technological developments, which are reflected in
      the improved spatial and temporal resolution of the images. High diagnostic
      accuracy has been achieved with 64- and more slice CT scanners and in selected
      patients, coronary CT angiography is regarded as a reliable alternative to
      invasive coronary angiography. Although the tremendous contributions of coronary
      CT angiography to cardiac imaging are acknowledged, appropriate use of cardiac CT
      as the first line technique by physicians has not been well established. Optimal
      selection of cardiac CT is essential to ensure acquisition of valuable diagnostic
      information and avoid unnecessary invasive procedures. This is of paramount
      importance since cardiac CT not only involves patient risk assessment, prediction
      of major cardiac events, but also impacts physician decision-making on patient
      management. Applications of CT in cardiac imaging include coronary artery calcium
      scoring for predicting the patient risk of developing major cardiac events,
      followed by coronary CT angiography which is commonly used to determine the
      diagnostic and prognostic accuracy in the coronary artery disease. This review
      presents an overview of the applications of CT in cardiac imaging in terms of
      coronary calcium scoring and coronary CT angiography. Judicious use of both
      cardiac CT tools will be discussed with regard to their value in different
      patient risk groups with the aim of identifying the appropriate criteria for
      choosing a cardiac CT modality. An effective diagnostic pathway is finally
      recommended to physicians for appropriate selection of cardiac CT in clinical
      practice.

PMID- 21724354
TI  - Reproductibility of apparent diffusion coefficients measurements in diffusion
      weighted MRI of the abdomen with different b values.
AB  - PURPOSE: To test the reproducibility of apparent diffusion coefficients (ADC)
      measurements of the normal liver, kidney and spleen parenchyma with different b
      values. MATERIALS AND METHODS: Eleven healthy volunteers were imaged twice with
      use of the same protocol. Each DWI was performed with b-factors of 0, 100 and 500
      s/mm(2). The ADCs were organized according to session (1 or 2), anatomic location
      and repetition (twice with two different b value per session). The ADC data were
      analyzed with repeated-measures analysis of variance to demonstrate the influence
      of anatomic location, session and different b values. The coefficient of
      variation was calculated for each subject, b value and anatomic location, then
      analyzed by using repeated-measures analysis of variance. RESULTS: There were
      significant differences in mean ADCs among the three anatomic locations and with
      different b values (P<.05). There were no significant differences in ADCs between
      imaging sessions 1 or 2 for both b values (P>.05). The CV values range between
      7.3% and 14.7%. There were no significant differences in CV values neither
      between the two b values nor for the various organ locations (P>.05). CONCLUSION:
      Using the same technical parameters, patients and the same observer, CV values
      range between 7.3% and 14.7%. And we recommend to be careful in examination and
      comparison of the measured ADC values, below these limits, without knowledge
      technical parameters that has been used, otherwise differences that are merely
      because of changes in the measurement technique could be interpreted as
      differences because of progression of disease or therapy.

PMID- 21724355
TI  - Interobserver agreement for sonograms of breast lesions obtained by an automated
      breast volume scanner.
AB  - OBJECTIVE: To evaluate the interobserver agreement of radiologists in the
      description and final assessment of breast sonograms obtained using an automated
      breast volume scanner (ABVS) using a unique descriptor of three-dimensional
      ultrasound (3D US) and the Breast Imaging Reporting and Data System (BI-RADS) US
      lexicon. METHODS: From October to December 2010, 208 patients were subjected to
      an ABVS examination in the supine position, and data were automatically sent to
      the ABVS workstation. Two radiologists independently evaluated 234 breast masses
      (148 benign and 86 malignant masses) using a unique descriptor from the 3D US and
      the BI-RADS US lexicon. The reviewers were blinded to the patient's mammographic
      images, medical history, and pathologic findings. The interobserver agreement was
      measured using kappa statistics. RESULTS: Substantial agreement was obtained for
      lesion shape, orientation, margin, echo pattern, posterior acoustic features,
      calcification and final assessment (kappa=0.79, 0.74, 0.76, 0.69, 0.68, 0.71 and
      0.70, respectively). Fair agreement was obtained for retraction phenomenon and
      lesion boundary (kappa=0.54 and 0.42, respectively). CONCLUSIONS: The
      interobserver agreement for breast sonograms obtained by ABVS is good, especially
      for lesion shape and margin; however, the interobserver agreement for the
      retraction phenomenon, which is a unique descriptor of coronal-plane 3D US, needs
      to be improved.

PMID- 21724356
TI  - Functional imaging of larynx via 256-Slice Multi-Detector Computed Tomography in
      patients with laryngeal tumors: a faster, better and more reliable pre
      therapeutic evaluation.
AB  - OBJECTIVE: To determine the clinical utility of using dynamic maneuvers during
      imaging of larynx via 256-Slice Multi-Detector Computed Tomography in the pre
      therapeutic evaluation of laryngeal tumors. MATERIALS AND METHODS: A total of 27
      patients (7 women, 20 men; aged 53-76 years) diagnosed with laryngeal squamous
      cell carcinoma were evaluated pre-therapeutically via contrast enhanced axial CT
      scans during consecutive phases of phonation (PP), inspiration (IP) and Valsalva
      maneuver (VP). RESULTS: In 2 of 5 patients diagnosed with T1a glottic tumor,
      scans obtained during VP and PP were normal while the CT scans obtained during IP
      clearly showed a mass. In all patients (27/27) PP provided visualization of the
      ventricle, on coronal plane images and the pyriform sinus apices, on axial plane
      images. Involvement of the anterior commissure was best assessable on axial plane
      IP images (sensitivity 93%, specificity 92%). In cases of stage T1-T3 tumors use
      of dynamic maneuvers during laryngeal CT imaging showed the location and
      extension of the tumor better than the single phase CT scans did. We did not find
      a significant improvement in the pre-therapeutic evaluation in stage T4 tumors.
      CONCLUSION: Providing markedly clearer and more detailed evaluation of mucosal
      surfaces and deep structures of the larynx and mobility of the cords than do
      conventional scans, use of dynamic laryngeal maneuvers during laryngeal CT
      imaging seems to be an useful alternative in the pre-therapeutic assessment of
      laryngeal tumors.

PMID- 21724357
TI  - Evaluation of tomosynthesis elastography in a breast-mimicking phantom.
AB  - OBJECTIVE: To evaluate whether measurement of strain under static compression in
      tomosynthesis of a breast-mimicking phantom can be used to distinguish tumor
      simulating lesions of different elasticities and to compare the results to values
      predicted by rheometric analysis as well as results of ultrasound elastography.
      MATERIALS AND METHODS: We prepared three soft breast-mimicking phantoms
      containing simulated tumors of different elasticities. The phantoms were imaged
      using a wide angle tomosynthesis system with increasing compression settings
      ranging from 0 N to 105 N in steps of 15 N. Strain of the inclusions was measured
      in two planes using a commercially available mammography workstation. The
      elasticity of the phantom matrix and inclusion material was determined by
      rheometric analysis. Ultrasound elastography of the inclusions was performed
      using two different ultrasound elastography algorithms. RESULTS: Strain at
      maximal compression was 24.4%/24.5% in plane 1/plane 2, respectively, for the
      soft inclusion, 19.6%/16.9% for the intermediate inclusion, and 6.0%/10.2% for
      the firm inclusion. The strain ratios predicted by rheometrical testing were
      0.41, 0.83 and 1.26 for the soft, intermediate, and firm inclusions,
      respectively. The strain ratios obtained for the soft, intermediate, and firm
      inclusions were 0.72+/-0.13, 1.02+/-0.21 and 2.67+/-1.70, respectively for
      tomosynthesis elastography, 0.91, 1.64 and 2.07, respectively, for ultrasound
      tissue strain imaging, and 0.97, 2.06 and 2.37, respectively, for ultrasound real
      time elastography. CONCLUSIONS: Differentiation of tumor-simulating inclusions by
      elasticity in a breast mimicking phantom may be possible by measuring strain in
      tomosynthesis. This method may be useful for assessing elasticity of breast
      lesions tomosynthesis of the breast.

PMID- 21724358
TI  - Assessment of colorectal hepatic metastases by quantitative T2 relaxation time.
AB  - AIM: To determine the T(2) relaxation time of colorectal hepatic metastases and
      changes in T(2) relaxation times following chemotherapy. MATERIALS AND METHODS:
      42 patients with 96 hepatic colorectal metastases underwent baseline MRI. Axial
      T(1), T(2) and multi-echo GRASE sequences were acquired. ROIs were drawn on T(2)
      relaxation maps, obtained from GRASE images, encompassing metastasis and normal
      liver to record T(2) relaxation time values. In 11 patients with 28 metastases,
      MRI was repeated using same protocol at 6 weeks following chemotherapy. The
      median pre-treatment T(2) values of metastases and normal liver were compared
      using the Mann-Whitney test. The pre- and post-treatment median T(2) values of
      metastases were compared using the Wilcoxon-Rank test for responding (n=16) and
      non-responding (n=12) lesions defined by RECIST criteria. The change in T(2)
      values (DeltaT(2)) were compared and correlated with percentage change in lesion
      size. RESULTS: There was no difference in the pre-treatment median T(2) of
      metastases between responding (67.3+/-8.6) and non-responding metastases (71.4+/
      16.5). At the end of chemotherapy, there was a decrease in the median T(2) of
      responding lesions (61.6+/-12.6) p=0.83, and increase in non-responding lesions
      (76.2+/-18.4) p=0.03, but these were not significantly different from the pre
      treatment values. There was no significant difference in DeltaT(2) of responding
      and non-responding lesions (p=0.18) and no correlation was seen between size
      change and DeltaT(2) (coefficient=0.3). CONCLUSION: T(2) relaxation time does not
      appear to predict response of colorectal liver metastasis to chemotherapy.

PMID- 21724359
TI  - Chiral HPLC studies on chemical behavior of 6-methoxydihydrosanguinarine in
      alcoholic solvent system.
AB  - All the enantiomers of methoxydihydrosanguinarine (MS), ethoxydihydrosanguinarine
      (ES) and iso-propoxydihydrosanguinarine (PS) were separated by chiral HPLC. They
      were further identified by comparing the retention times of authentic standards
      as well as LC-MS. Interestingly, the approximately same conversion rates for the
      formation MS from ES or PS and the slower conversion of MS in isopropanol
      compared to ethanol demonstrated two step mechanism in the reaction of
      alkoxysanguinarine in alcohols, which is composed of the initial formation of
      sanguinarine as a planar intermediate and the addition of alcohol to intermediate
      as possible rate limiting step. Thus, sanguinarine has a pivotal role in the
      chemical behavior of alkoxysanguinarine in alcoholic solvents. Such possible
      variation of the structure of sanguinarine may be the source of its diverse
      biological activities.

PMID- 21724360
TI  - [Renal-nerve ablation in patients with resistant hypertension: caution is still
      needed].
AB  - The autonomic nervous system plays a major role in blood pressure regulation and
      pathogenesis of essential hypertension. Before the advent of orally active
      antihypertensive treatments, surgical sympathectomy was the only therapeutic
      option in severely hypertensive patients. It was effective in reducing blood
      pressure in half of these patients. However, this intervention was associated
      with high incidence of severe adverse events, including death. It was abandoned
      in the 1960s with the advent of effective and well tolerated antihypertensive
      drugs. In the 2010s, despite availability of multiple classes of antihypertensive
      agents, a significant proportion of patient have resistant hypertension, i.e.
      remain uncontrolled despite the use of optimal doses of three antihypertensive
      agents, including a diuretic. Catheter-based renal denervation is a new approach
      for the treatment of resistant hypertension developed since 2008. Clinical
      studies have shown that it decreases blood pressure on the short- and mid-term
      and has a good tolerability profile. However, the blood pressure response
      following this intervention has only been evaluated in a small number of highly
      selected patients in open-label studies and infrequent or delayed adverse events
      cannot be still fully excluded. Catheter-based renal denervation opens new
      interesting therapeutic perspectives. At this stage of development, the technique
      should still be evaluated before its widespread diffusion.

PMID- 21724361
TI  - [Uveitis].
AB  - Uveitis is an encompassing term for intraocular inflammation. Particularly
      heterogeneous presentations may be observed. Uveitis may belong to the
      manifestations of a general disease or may affect only the eye. Causes of uveitis
      are inflammatory or infectious. Finding the cause of uveitis is based on
      analyzing the ocular phenotype and extraocular manifestations when present. The
      main factor for the prognosis of uveitis is its consequences on the macula. The
      treatment of uveitis is based on its cause and on its severity.

PMID- 21724362
TI  - Confirmatory factor analysis of posttraumatic stress symptoms in Brazilian
      primary care patients: an examination of seven alternative models.
AB  - The DSM-IV-TR postulates that PTSD symptoms are organized into 3 clusters. This
      assumption has been challenged by growing number of factor analytical studies,
      which tend to favor 4-factor, first-order models. Our objective was to
      investigate whether the clusters of PTSD symptoms identified in North American
      and European studies could be replicated in a Brazilian sample composed of 805
      primary care patients living in hillside slums. Volunteers were asked to fill out
      the Brazilian version of the Posttraumatic Stress Disorder Checklist-Civilian
      Version and a confirmatory factor analysis of this scale was conducted with the
      software LISREL 8.80. Seven models were tested and a 4-factor, first-order
      solution including an emotional numbing cluster was found to provide the best
      fit. Although PTSD has been characterized by some critics as a Western culture
      specific disorder lacking universal validity, our results seem to uphold the
      cross-cultural validity of the 4-factor, first-order model.

PMID- 21724363
TI  - Developing and refining the Taiwan Birth Cohort Study (TBCS): five years of
      experience.
AB  - The Taiwan Birth Cohort Study (TBCS) is the first nationwide birth cohort
      database in Asia designed to establish national norms of children's development.
      Several challenges during database development and data analysis were identified.
      Challenges include sampling methods, instrument development and statistical
      approach to missing data. The purpose of this paper is to describe the pilot
      study underpinning the TBCS, testing of the TBCS developmental instrument and the
      resolution of methodological challenges. Bayesian analysis fill in missing data,
      three-step regression analysis for the investigation of mediating and moderating
      effect, the use of structural equation modeling in a large scale investigation,
      investigating direct and indirect effects, confounding factors and reciprocal
      relationships in children's development, and used latent growth model in
      longitudinal observations are described. The TBCS will provide ongoing
      longitudinal information regarding the predisposing and maintaining factors
      affecting the long term outcome of pediatric illnesses.

PMID- 21724364
TI  - Videographic documentation of an open cyst converting into a sulcus vocalis.
AB  - STUDY DESIGN: Case study. DISCUSSION: The origin of sulcus vocalis is debatable,
      it may arise from a congenital or acquired cyst that ruptures leaving a sulcus
      attached to the deep layer of the lamina propria. This has been hypothesized but
      never shown before. CONCLUSION: In this article, we present the first
      videographic documentation of an intracordal cyst that over time may have become
      a sulcus vocalis.

PMID- 21724365
TI  - Activity patterns in latissimus dorsi and sternocleidomastoid in classical
      singers.
AB  - OBJECTIVES: The aim of this study was to investigate and compare the roles of the
      accessory respiratory muscles, latissimus dorsi (LD), and sternocleidomastoid, in
      classical singing. METHODS: Electromyography was used to record the activity of
      these muscles in six classically trained female singers carrying out a number of
      singing and nonsinging tasks. Movements of the chest and abdominal walls were
      monitored simultaneously using inductive plethysmography, and the sound of the
      phonations was recorded. RESULTS: In normal breathing, LD is active transiently
      during very deep inhalations and in inhalation against resistance. During
      exhalation it becomes active again as residual capacity is approached or when air
      is expelled with great force. Sternocleidomastoid (SCM) supports inhalation when
      lung volume nears 100% vital capacity or when this is very rapid. All singers
      engaged LD in supported singing where it was associated with maintaining an
      expanded thorax. In coloratura singing, pulses of activity of increasing
      amplitude were often seen in LD toward the end of the breath. These were
      synchronized with each note. During a short phrase typical of the end of an aria,
      which was sung at full volume with the projected voice, both LD and SCM were
      active simultaneously. Spectral analysis of muscle activity demonstrated that in
      some singers, activity in LD and more rarely SCM, fluctuated in phase with
      vibrato. CONCLUSIONS: LD appears to play a significant role in maintaining chest
      expansion and the dynamic processes underlying vibrato and coloratura singing in
      classically trained singers.

PMID- 21724366
TI  - A small absorbable stent for treatment of anterior glottic web.
AB  - A new one-stage approach for treatment of selected anterior glottic web has been
      successful. This case report illustrates its simplicity in microlaryngoscopy with
      complete lysis of the anterior glottic web by CO(2) laser. Then a small neck
      horizontal incision is made at the level of anterior commissure to gain exposure
      to thyroid cartilage. Absorbable suture is passed through the midline of thyroid
      cartilage below and above the anterior commissure. A knot is tied over thyroid
      ala. The suture acts as a tiny stent to prevent recurrence of the web.

PMID- 21724367
TI  - Vocal handicap and quality of life after treatment of advanced squamous carcinoma
      of the larynx and/or hypopharynx.
AB  - OBJECTIVE/HYPOTHESIS: To evaluate and correlate voice-specific quality of life
      (QOL) and health-related QOL (HR-QOL) after treatment for advanced cancer of the
      larynx and/or hypopharynx. STUDY DESIGN: Cross-sectional study. METHODS: Patients
      submitted to partial laryngectomy (PL), salvage PL (sPL), concomitant
      radiotherapy and chemotherapy (RT+Chemo), total laryngectomy (TL), salvage TL
      (sTL), total pharyngolaryngectomy (TP) and salvage total pharyngolaryngectomy
      (sTP). The following questionnaires were used: (1) Voice Handicap Index (VHI) and
      (2) University of Washington Quality of Life Questionnaire (UW-QOL; version 4).
      RESULTS: Eighty-four patients participated in the study. All the patients PL
      (10), sPL (1), and RT+Chemo (24) communicated by laryngeal voice. Of the 49
      patients submitted to total removal of the larynx, 30 communicated with
      alaryngeal phonation, the major part being tracheoesophageal prosthesis (17). The
      worst subscale of VHI for the total patient group was functional (mean=13.15),
      and the value of the total score was 31. Patients submitted to PL, RT+Chemo, and
      TL presented slight handicap (medians of 27, 14, and 21.5, respectively).
      Patients treated with sTL, TP, and sTP presented moderate handicap (medians of
      45, 37.5, and 31.5, respectively). HR-QOL was considered between good and
      excellent for 78.6% of the patients, and poor for 21.4%. The correlation between
      voice-specific QOL and HR-QOL was significant (P=0.0001). CONCLUSION: Patients
      treated for advanced cancer of the larynx/hypopharynx present slight to moderate
      voice handicap and good/excellent HR-QOL. Stricter analysis of both the VHI and
      UW-QOL data suggests that more attention be given to the vocal handicap of the
      individual patient.

PMID- 21724368
TI  - Detecting inaudible vocal organ changes through glottal inverse filtering.
AB  - The aim of this study was to investigate if there were objective quantities
      extracted from the speech pressure waveforms that underlay inaudible changes in
      the symptoms of the vocal organ. This was done through analyzing 180 voice
      samples obtained from nine subjects (five females and four males) before and
      after exposure to a placebo substance (lactose) and an organic dust substance.
      Acoustical analysis of the voice samples was achieved by using glottal inverse
      filtering. Results showed that the values of primary open quotient and primary
      speed quotient changed significantly (P<0.05) as did the amplitude quotient
      (P<0.01). Exposure to lactose resulted in significant changes of secondary open
      quotient (P<0.05) but opposite to effects found for exposure to organic dust.
      Modeling of the vocal tract into cross-sectional planes revealed that the
      immediate plane above the vocal folds correlates inversely with the feeling that
      voice is tense, or feeling the need to make an effort when speaking in addition
      having a feeling of shortness of breath or the need to gasp for air. Such results
      may point to acoustically detected subclinical changes in the vocal organ that
      the subject him/herself feels while they remain perceptually undetected by
      others.

PMID- 21724369
TI  - Cepstral analysis of sexually appealing voice.
AB  - OBJECTIVES OF THE STUDY: In spite of voice being an important parameter of mate
      choice, none of the studies have described the acoustic characteristics of the
      sexually appealing voice. METHOD: Two hundred adults (100 men and 100 women) in
      the age range of 18-24 years were asked to narrate a topic, which was recorded
      directly onto Computerized Speech Lab (CSL) 6103 hardware. Recorded stimuli were
      presented to the six judges, and they were asked to indicate if the voice is
      sexually appealing on a five-point rating scale. The voices, which are
      consistently identified as sexually very attractive and unattractive were
      subjected to cepstral analysis through CSL. RESULTS: The results of perceptual
      analysis revealed that 28 of the female voice samples and 39 of the male voice
      samples were rated as sexually attractive. These ratings were consistent within
      and across the judges. The cepstral analysis was then performed in all the voice
      samples and the results of independent t test revealed higher values of cepstral
      peak parameter (CPP) in the sexually attractive voices in comparison to the other
      voice samples in both the genders. The obtained results are discussed with
      respect to the harmonic organization in the voice samples. CONCLUSIONS: The
      results of cepstral analysis in sexually attractive voices revealed higher values
      of CPP in comparison to the voices rated as sexually not appealing. This could be
      because of the presence of well-defined harmonic structure evidenced in the
      sexually appealing voice in comparison to voices rated as very unappealing. Our
      findings suggest that cepstral analysis is a good indicator of sexually appealing
      voice.

PMID- 21724371
TI  - Impact of noise structure and network topology on tracking speed of neural
      networks.
AB  - Understanding why neural systems can process information extremely fast is a
      fundamental question in theoretical neuroscience. The present study investigates
      the effect of noise on accelerating neural computation. To evaluate the speed of
      network response, we consider a computational task in which the network tracks
      time-varying stimuli. Two noise structures are compared, namely, the stimulus
      dependent and stimulus-independent noises. Based on a simple linear integrate-and
      fire model, we theoretically analyze the network dynamics, and find that the
      stimulus-dependent noise, whose variance is proportional to the mean of external
      inputs, has better effect on speeding up network computation. This is due to two
      good properties in the transient network dynamics: (1) the instant firing rate of
      the network is proportional to the mean of external inputs, and (2) the
      stationary state of the network is robust to stimulus changes. We investigate two
      network models with varying recurrent interactions, and find that recurrent
      interactions tend to slow down the tracking speed of the network. When the
      biologically plausible Hodgkin-Huxley model is considered, we also observe that
      the stimulus-dependent noise accelerates neural computation, although the
      improvement is smaller than that in the case of linear integrate-and-fire model.

PMID- 21724370
TI  - Three-dimensional visual feature representation in the primary visual cortex.
AB  - In the cat primary visual cortex, it is accepted that neurons optimally
      responding to similar stimulus orientations are clustered in a column extending
      from the superficial to deep layers. The cerebral cortex is, however, folded
      inside a skull, which makes gyri and fundi. The primary visual area of cats, area
      17, is located on the fold of the cortex called the lateral gyrus. These facts
      raise the question of how to reconcile the tangential arrangement of the
      orientation columns with the curvature of the gyrus. In the present study, we
      show a possible configuration of feature representation in the visual cortex
      using a three-dimensional (3D) self-organization model. We took into account
      preferred orientation, preferred direction, ocular dominance and retinotopy,
      assuming isotropic interaction. We performed computer simulation only in the
      middle layer at the beginning and expanded the range of simulation gradually to
      other layers, which was found to be a unique method in the present model for
      obtaining orientation columns spanning all the layers in the flat cortex.
      Vertical columns of preferred orientations were found in the flat parts of the
      model cortex. On the other hand, in the curved parts, preferred orientations were
      represented in wedge-like columns rather than straight columns, and preferred
      directions were frequently reversed in the deeper layers. Singularities
      associated with orientation representation appeared as warped lines in the 3D
      model cortex. Direction reversal appeared on the sheets that were delimited by
      orientation-singularity lines. These structures emerged from the balance between
      periodic arrangements of preferred orientations and vertical alignment of the
      same orientations. Our theoretical predictions about orientation representation
      were confirmed by multi-slice, high-resolution functional MRI in the cat visual
      cortex. We obtained a close agreement between theoretical predictions and
      experimental observations. The present study throws a doubt about the
      conventional columnar view of orientation representation, although more
      experimental data are needed.

PMID- 21724372
TI  - How refractory is refractory epilepsy? Patterns of relapse and remission in
      people with refractory epilepsy.
AB  - BACKGROUND: Outcome studies in people with epilepsy have largely focused on the
      prognosis in the early stages and factors predictive of early remission. Few
      studies have examined prognosis in chronic refractory epilepsy. METHODS: We
      determined the pattern of remission and relapse of epilepsy in a cohort of people
      with refractory epilepsy (seizures in the past two years, at least five years
      after onset and who have been treated with at least 2 appropriate antiepileptic
      drugs during that time) to investigate whether any clinical or demographic
      features are predictive of seizure patterns. Seizure patterns were defined as
      intermittent (at least one previous period of remission of two or more years with
      a subsequent relapse) or continuous (no periods of remission of two years or more
      since seizure onset). We correlated clinical variables with these patterns. We
      devised a prognostic model summarising patterns of remission and relapse over
      time in epilepsy. RESULTS: 290 people were recruited, of whom 70% had a
      continuous pattern of seizures with the remaining 30% having an intermittent
      pattern. The only clinical variables which significantly differed between the two
      groups were a higher total number of antiepileptic drugs taken by those in the
      continuous group (P=0.01) and fewer seizures in the previous year in the
      intermittent group (P<0.001). A prognostic model of epilepsy is proposed.
      CONCLUSION: There is considerable heterogeneity in long-term seizure patterns in
      people who do not enter long-term remission in the early years after diagnosis.

PMID- 21724373
TI  - Sleep correlates of cognition in early course psychotic disorders.
AB  - BACKGROUND: Slow waves and sleep spindles, the main oscillations during non-rapid
      eye movement sleep, have been thought to be related to cognitive processes, and
      are impaired in psychotic disorders. Cognitive impairments, seen early in the
      course of psychotic disorders, may be related to alterations in these
      oscillations, but few studies have examined this relationship. METHOD: Twenty
      seven untreated patients with a recently diagnosed psychotic disorder had
      polysomnographic sleep studies and neuro-cognitive testing. RESULTS: Reduced
      power in the sigma range, which reflects spindle density, was associated with
      impaired attention, and reasoning, but not intelligence quotient (IQ). Slow wave
      sleep measures were not significantly associated with any cognitive measures.
      CONCLUSIONS: Impairments in sleep spindles may be associated with cognitive
      deficits in the early course of psychotic disorders. These observations may help
      clarify neuro-biologic mechanisms of cognitive deficits in psychotic disorders
      such as schizophrenia.

PMID- 21724374
TI  - Diverse prevalence of 16S rRNA methylase genes armA and rmtB amongst clinical
      multidrug-resistant Escherichia coli and Klebsiella pneumoniae isolates.
AB  - In this study, 112 Escherichia coli and 55 Klebsiella pneumoniae isolates with a
      multidrug-resistant (MDR) phenotype were collected from 2007 to 2009. All
      isolates simultaneously exhibited resistance to cefotaxime (or ceftazidime),
      ciprofloxacin (or levofloxacin) and amikacin. Plasmid-mediated 16S rRNA
      methylases, including armA, rmtA, rmtB, rmtC, rmtD, rmtE and npmA, were detected
      by polymerase chain reaction (PCR) amplification. Common beta-lactamase genes,
      including bla(TEM), bla(SHV), bla(CTX-M), bla(PER), bla(VEB), bla(GES) and
      bla(OXA), as well as plasmid-mediated bla(AmpC) and plasmid-mediated quinolone
      resistance (PMQR) determinants, including qnrA, qnrB, qnrS, qepA and aac(6')-Ib
      cr, were also screened. The transferable capacity of resistance plasmids was
      established by conjugation testing. The genetic relatedness of isolates was
      analysed by pulsed-field gel electrophoresis (PFGE). Only armA and rmtB genes
      were detected in this study. Data showed that 93.8% of MDR E. coli and 94.5% of
      MDR K. pneumoniae carried at least one of armA or rmtB. The armA and rmtB genes
      were present in 11.6% and 82.1% of MDR E. coli, respectively. In parallel, 58.2%
      and 40.0% of MDR K. pneumoniae were armA- and rmtB-positive, respectively.
      Furthermore, the qepA gene was present in 66.3% of rmtB-carrying MDR E. coli, but
      it was rarely detected in MDR K. pneumoniae. Approximately 71.9% of armA-positive
      MDR K. pneumoniae simultaneously co-carried qnrB and bla(DHA). Moreover, 78.1%
      and 63.6%, respectively, of armA-positive and rmtB-positive MDR K. pneumoniae
      strains harboured qnr alleles and 53.1% and 59.1% harboured aac(6')-Ib-cr. In
      addition, MDR E. coli strains exhibited a low prevalence of qnr alleles and
      aac(6')-Ib-cr. PFGE analysis revealed divergent genetic relatedness, suggesting
      horizontal dissemination of armA and rmtB along with common beta-lactamases and
      PMQR determinants amongst clinical MDR E. coli and K. pneumoniae isolates.

PMID- 21724375
TI  - Resistance of the Burkholderia cepacia complex to fosmidomycin and fosmidomycin
      derivatives.
AB  - The Burkholderia cepacia complex (BCC) is a group of 17 closely related
      opportunistic pathogens that are able to infect the respiratory tract of cystic
      fibrosis patients. BCC bacteria are intrinsically resistant to many antibiotics
      and are therefore difficult to eradicate. Fosmidomycin could be a new therapeutic
      agent to treat BCC infections as it inhibits 1-deoxy-d-xylulose-5-phosphate
      reductoisomerase (Dxr), a key enzyme in the non-mevalonate pathway essential in
      BCC bacteria for isoprenoid synthesis. In this study, the antimicrobial activity
      of fosmidomycin and eight fosmidomycin derivatives towards 40 BCC strains was
      investigated. All BCC strains were resistant to fosmidomycin, although addition
      of glucose-6-phosphate reduced the minimum inhibitory concentration values of
      FR900098, the fosmidomycin acetyl derivative, from 512 mg/L to 64 mg/L for
      Burkholderia multivorans and B. cepacia. This enhanced activity was linked to
      increased expression of the genes involved in glycerol-3-phosphate transport,
      which appears to be the only route for fosmidomycin import in BCC bacteria.
      Furthermore, upregulation of a fosmidomycin resistance gene (fsr) encoding an
      efflux pump was observed during fosmidomycin and FR900098 treatment. These
      results strongly suggest that the observed resistance in BCC bacteria is due to
      insufficient uptake accompanied by fosmidomycin and FR900098 efflux.

PMID- 21724376
TI  - Protein adsorption behaviors onto photocatalytic Ti(IV)-doped calcium
      hydroxyapatite particles.
AB  - The fundamental experiments on the adsorption behaviors of proteins onto
      photocatalytic Ti(4+)-doped calcium hydroxyapatite (TiHap) particles were
      examined comparing to those onto the calcium hydroxyapatite (CaHap) and
      commercially available typical titanium oxide (TiO(2)) photocatalyst (TKP-101).
      The heat treated TiHap and CaHap particles were also used after treated these
      particles at 650 degrees C for 1h (abbreviated as TiHap650 and CaHap650,
      respectively). All the adsorption isotherms of bovine serum albumin (BSA),
      myoglobin (MGB) and lysozyme (LSZ) from 1*10(-4)mol/dm(3) KCl solution were the
      Langmuirian type. The saturated amounts of adsorbed BSA (n(s)(BSA)) for the
      CaHap650 particles was higher than that for CaHap. Similar results were observed
      for TiHap and TiHap650. The adsorption of LSZ exhibited the same result of BSA,
      while the saturated amounts of adsorbed LSZ (n(s)(LSZ)) value on the TiHap were
      much higher than CaHap. However, the saturated amounts of adsorbed MGB
      (n(s)(MGB)) are almost equal to those for the CaHap and TiHap nevertheless
      whether these particles were heat treated at 650 degrees C or not. The TKP-101
      exhibited extremely small adsorption capacity of all proteins due to its small
      particle size of ca. 4nm in diameter. The independence of the n(s)(MGB) value on
      the zeta potential (zp) of the particles was explained by the electrostatical
      neutrality of MGB molecules. On the other hand, the n(s)(LSZ) values were
      increased with increase in the negative zp of the particles. This fact was
      explained by increasing the electrostatic attractive forces between negatively
      charged particles and positively charged LSZ. However, the n(s)(BSA) values
      exhibit maxima for the heat treated TiHap650 and CaHap650 particles. This result
      was interpreted to the formation of beta-TCP crystal phase by the heat treatment.
      The produced Ca(2+) ions by dissolution from beta-TCP phase may exert as binders
      between BSA and surfaces of the heat treated particles.

PMID- 21724377
TI  - Voltammetric determination of cefpirome at multiwalled carbon nanotube modified
      glassy carbon sensor based electrode in bulk form and pharmaceutical formulation.
AB  - A new, simple and low cost voltammetric method for the determination of cefpirome
      in pharmaceutical preparations has been developed using multiwalled carbon
      nanotube modified glassy carbon electrode (MWCNT), which showed stable response
      with enhanced selectivity and sensitivity over the bare glassy carbon electrode.
      A multiwalled carbon nanotube (MWCNT) modified glassy carbon electrode (GCE) is
      used for the simultaneous determination of cefpirome by differential pulse
      voltammetry and square wave voltammetry. Results indicated that cathodic peak of
      cefpirome is greatly improved at MWCNT modified GC electrode as compared with the
      bare GC electrode showing excellent electrocatalytic activity towards cefpirome
      reduction. Linear calibration curves are obtained over the concentration range
      100-600 MUg mL(-1) in Britton Robinson buffer at pH 4.51 with limit of detection
      (LOD) and limit of quantification (LOQ) are 0.647 MUg mL(-1) and 2.159 MUg mL(-1)
      using SWV and 5.540 MUg mL(-1) and 18.489 MUg mL(-1) using DPV, respectively. The
      described method is rapid and can be successfully applied for the determination
      of cefpirome in bulk form and pharmaceutical formulations.

PMID- 21724378
TI  - Soybean isoflavone genistein regulates apoptosis through NF-kappaB dependent and
      independent pathways.
AB  - Cyclooxygenase-2 (COX-2), the key enzyme of the conversion of arachidonic acid to
      prostaglandins is an important regulator of inflammation and perhaps apoptosis.
      Genistein is an active component of legumes and other related food associated
      with prevention of degenerative diseases possibly through modulating certain
      signaling pathways. It was investigated whether the induction of apoptosis with
      genistein was carried out via COX-2 suppression through the regulation of NF
      kappaB. The cox-2 positive and negative cells were used to compare the effect of
      genistein on the modulation of NF-kappaB in COX-2 expressed or non-expressed
      genotypic systems. Suppression of COX-2 as well as decreasing NF-kappaB DNA
      binding activity was accompanied with the induction of apoptosis in genistein
      treated COX-2 expressed cells. However, in cox-2 negative cells, apoptosis
      occurred without any involvement of NF-kappaB with genistein treatement.
      Genistein induced apoptosis through the generation of reactive oxygen species
      (ROS) both of cox-2 positive and negative cells. These results suggested that
      genistein is capable of exihibiting NF-kappaB-dependent and NF-kappaB-independent
      apoptotic control via ROS generation depending on genetic cell types.

PMID- 21724379
TI  - Nonylphenol decreases viability and arrests cell cycle via reactive oxygen
      species in Raji cells.
AB  - 4-Nonylphenol (NP), an environmental contaminant commonly found in water systems,
      has been documented to have adverse effects on human health. In the current
      study, the effects of NP on the survival, reactive oxygen species (ROS)
      production and cell cycle distribution of human Raji cells, a human
      lymphoblastoid cell line with B cell characteristics, were investigated.
      Furthermore, N-Acetyl-Cysteine (NAC) was used to explore the underlying
      mechanisms. The results showed that NP dramatically reduced cell viability along
      with the induction of ROS in a dose dependent manner, and cell survival was
      recovered by NAC pretreatment. Most strikingly, NP exposure altered the cell
      cycle profile, mainly leading to the accumulation of cells in the G2/M phase.
      Pretreatment of Raji cells with NAC attenuated the NP-induced G2/M cell cycle
      arrest. Taken together, the results suggest NP exhibits cytotoxic effects on Raji
      cells by decreasing cell viability and inducing G2/M cell cycle arrest, in a ROS
      dependent manner.

PMID- 21724380
TI  - On the terminology of cranial nerves.
AB  - The present contribution adopts various points of view to discuss the terminology
      of the twelve nervi craniales. These are paired nerves and have dual names, terms
      with Roman ordinal numerals, i.e., the nerves are numbered in the top-to-bottom
      direction, and descriptive historical names. The time of origin and motivation
      behind the investigated terms are determined. The majority of terms come from the
      17th and 18th centuries. The motivation behind most of them is (a) nerve
      localization, as this is in conformity with anatomical nomenclature in general,
      (b) nerve function, and rarely (c) nerve appearance. The occurrence of synonymous
      names and variants is also a focus of attention. In several cases, reference is
      made to the process called terminologization, meaning when a certain expression
      acquires technical meaning and the characteristic/feature of the term.

PMID- 21724381
TI  - Polymer--drug conjugates as nano-sized medicines.
AB  - Polymer Therapeutics have enormously evolved in the past decades. Several
      polymeric drugs as well as polymer-protein conjugates have been in the market
      since the 90s, but although polymer-drug conjugates are already in clinical
      trials they still need to reach this final goal. There are four main convergent
      strategies to move this platform technology further. First, exploitation of new
      molecular targets in cancer therapy and design of polymer-drug conjugates as
      treatments for other diseases. Second, the development of combination therapy.
      Third, attempts to improve polymer chemistry, including the use of new well
      defined architectures and the optimization of the advanced characterization
      techniques essential to transform a promising conjugate into a candidate for
      clinical evaluation. Finally, increased understanding of polymer conjugate
      features that govern clinical risk-benefit is leading to an appreciation of
      clinical biomarkers that will open new possibilities for personalized therapy.

PMID- 21724382
TI  - Behavioural and cognitive neuroscience.

PMID- 21724383
TI  - A comparison of inflammation-based prognostic scores in patients with cancer. A
      Glasgow Inflammation Outcome Study.
AB  - INTRODUCTION: Components of the systemic inflammatory response, combined to form
      inflammation-based prognostic scores (modified Glasgow Prognostic Score (mGPS),
      Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic
      Index (PI), Prognostic Nutritional Index (PNI)) have been associated with cancer
      specific survival. The aim of the present study was to compare the prognostic
      value of these scores. METHODS: Patients (n=27,031) who had an incidental blood
      sample taken between 2000 and 2007 for C-reactive protein, albumin, white cell,
      neutrophil, lymphocyte and platelet counts, as well as a diagnosis of cancer
      (Scottish Cancer Registry) were identified. Of this group 8759 patients who had
      been sampled within two years following their cancer diagnosis were studied.
      RESULTS: On follow up, there were 5163 deaths of which 4417 (86%) were cancer
      deaths. The median time from blood sampling to diagnosis was 1.7 months. An
      elevated mGPS, NLR, PLR, PI and PNI were predictive of a reduced cancer specific
      survival independent of age, sex and deprivation and tumour site (all p<0.001).
      The area under the receiver operator curves was greatest for mGPS and PI.
      Specifically, in colorectal cancer, an elevated mGPS and PI were predictive of a
      reduced cancer specific survival independent of age, sex, deprivation and tumour
      stage (both p<0.001). CONCLUSION: The results of the present study show that
      systemic inflammation-based scores, in particular the mGPS and PI, have
      prognostic value in cancer independent of tumour site. Based on the present
      results and the existing validation literature, the mGPS should be included in
      the routine assessment of all patients with cancer.

PMID- 21724384
TI  - Impact of chlortetracycline on sequencing batch reactor performance for swine
      manure treatment.
AB  - Treatment of aged (500 day, 4 degrees C stored) chlortetracycline (CTC; 0, 20,
      40, 80 mg/L CTC)-amended swine manure using two cycle, 22 day stage anaerobic
      sequencing batch reactors (SBR) was assessed. Eighty milligrams per liter CTC
      treatment inhibited SBR treatment efficiencies, although total gas production was
      enhanced compared to the no-CTC treatment. The 20 and 40 mg/L CTC treatments
      resulted in either slight or no differences to SBR treatment efficiencies and
      microbial diversities compared to the no-CTC treatment, and were generally
      similar to no-CTC treatments upon completion of the first 22 day SBR cycle. All
      CTC treatments enhanced SBR gas generation, however CH(4) yields were lowest for
      the 80 mg/L CTC treatment (0.111L CH(4)/g tCOD) upon completion of the second SBR
      react cycle. After a 22 day acclimation period, the 80 mg/L CTC treatment
      inhibited methanogenesis due to acetate accumulation, and decreased microbial
      diversity and CH(4) yield compared to the no-CTC treatment.

PMID- 21724385
TI  - A thermodynamic analysis of electron production during syngas fermentation.
AB  - Currently, syngas fermentation is being developed as one option towards the
      production of biofuels from biomass. This process utilizes the acetyl-CoA (Wood
      Ljungdahl) metabolic pathway. Along the pathway, CO and CO(2) are used as carbon
      sources. Electrons required for the metabolic process are generated from H(2)
      and/or from CO. This study showed that electron production from CO is always more
      thermodynamically favorable compared to electron production from H(2) and this
      finding is independent of pH, ionic strength, gas partial pressure, and electron
      carrier pairs. Additionally, electron production from H(2) may be
      thermodynamically unfavorable in some experimental conditions. Thus, it is
      unlikely that H(2) can be utilized for electron production in favor of CO when
      both species are present. Therefore, CO conversion efficiency will be sacrificed
      during syngas fermentation since some of the CO will provide electrons at the
      expense of product and cell mass formation.

PMID- 21724386
TI  - Preparation of high adsorption capacity bio-chars from waste biomass.
AB  - Bio-chars with high adsorption capacity derived from rice-husks and corncobs were
      prepared at different retention times (RTs) in a pyrolysis reactor. At a fixed
      pyrolysis temperature, the pyrolysis RT is a key factor influencing the surface
      areas and functional group contents of the bio-chars, and further influencing
      their adsorption capacities. The results indicate that the bio-char prepared at
      RT of 1.6s exhibits a higher phenol adsorption capacity (589 mg g(-1)) than other
      bio-chars and many activated carbons reported in the literature. An adsorption
      mechanism based on acid-base interaction and hydrogen binding between phenol and
      the functional groups was proposed to elucidate the adsorption process. An
      economic evaluation of the use of bio-chars as adsorbents was made.

PMID- 21724387
TI  - Energy and exergy analyses of a biomass-based hydrogen production system.
AB  - In this paper, a novel biomass-based hydrogen production plant is investigated.
      The system uses oil palm shell as a feedstock. The main plant processes are
      biomass gasification, steam methane reforming and shift reaction. The modeling of
      the gasifier uses the Gibbs free energy minimization approach and chemical
      equilibrium considerations. The plant, with modifications, is simulated and
      analyzed thermodynamically using the Aspen Plus process simulation code (version
      11.1). Exergy analysis, a useful tool for understanding and improving efficiency,
      is used throughout the investigation, in addition to energy analysis. The overall
      performance of the system is evaluated, and its efficiencies become 19% for
      exergy efficiency and 22% energy efficiency while the gasifier cold gas
      efficiency is 18%.

PMID- 21724388
TI  - A mathematical model to design a lignocellulosic biofuel supply chain system with
      a case study based on a region in Central Texas.
AB  - This study formulates a model to maximize the profit of a lignocellulosic biofuel
      supply chain ranging from feedstock suppliers to biofuel customers. The model
      deals with a time-staged, multi-commodity, production/distribution system,
      prescribing facility locations and capacities, technologies, and material flows.
      A case study based on a region in Central Texas demonstrates application of the
      proposed model to design the most profitable biofuel supply chain under each of
      several scenarios. A sensitivity analysis identifies that ethanol (ETOH) price is
      the most significant factor in the economic viability of a lignocellulosic
      biofuel supply chain.

PMID- 21724389
TI  - Optimization of processing conditions for the pretreatment of wheat straw using
      aqueous ionic liquid.
AB  - Pretreatment of wheat straw with the aqueous ionic liquid, 1-ethyl-3
      methylimidazolium acetate, was optimized to maximize fermentable sugars recovery.
      The optimization process employed a central composite design, where the
      investigated variables were temperature (130-170 degrees C), time (0.5-5.5h) and
      ionic liquid concentration (0-100%). All the tested variables were identified to
      have significant effects (p<0.05) on fermentable sugars recovery. The optimum
      pretreatment conditions were 158 degrees C, an ionic liquid concentration of
      49.5% (w/w), and a duration of 3.6h. Cellulose and xylan digestibility generally
      increased with increasing temperature, time and ionic liquid concentration; but,
      the carbohydrates recovered in the washed solids following pretreatment
      decreased. Thus, the final optimum conditions for maximizing fermentable sugars
      from the starting biomass were a compromise between greater digestibility and
      minimal carbohydrates loss during pretreatment.

PMID- 21724390
TI  - Production of algal biomass (Chlorella vulgaris) using sediment microbial fuel
      cells.
AB  - In this study, a novel algal biomass production method using a sediment microbial
      fuel cell (SMFC) system was assessed. Under the experimental conditions, CO(2)
      generation from the SMFC and its rate of increase were found to be dependent on
      the current generated from the SMFC. However, the CH(4) production rate from the
      SMFC was inhibited by the generation of current. When Chlorella vulgaris was
      inoculated into the cathode compartment of the SMFC and current was generated
      under 10 Omega resistance, biomass production from the anode compartment was
      observed to be closely associated with the rate of current generation from the
      SMFC. The experimental results demonstrate that 420 mg/L of algae (dry cell
      weight) was produced when the current from the SMFC reached 48.5 mA/m(2).
      Therefore, SMFC could provide a means for producing algal biomass via CO(2)
      generated by the oxidation of organics upon current generation.

PMID- 21724391
TI  - Photosynthesis-Inhibiting efficiency of 4-chloro-2-(chlorophenylcarbamoyl)phenyl
      alkylcarbamates.
AB  - A series of photosynthetic electron transport (PET) inhibitors from the group of
      salicylanilide alkylcarbamates was investigated. The compounds were analyzed
      using RP-HPLC to determine lipophilicity, and their PET inhibition was determined
      in spinach (Spinacia oleracea L.) chloroplasts. The site of action of the studied
      compounds is situated at the donor site of photosystem 2 (PS 2). Compounds
      substituted by chlorine in C'-3 and C'-4 of the aniline ring and the optimal
      length of the alkyl chain pentyl-heptyl in the carbamate moiety provided the most
      active PET inhibitors (IC(50) inhibition <10 MUmol/L). Disubstitution in C'-3,4
      by chlorine caused significant PET inhibiting activity decrease. Nevertheless,
      for all three series of C'-3, C'-4, C'-3,4 compounds, the dependence of PET
      activity on lipophilicity showed to be quasi-parabolic.

PMID- 21724392
TI  - Rigidized 1-aryl sulfonyl tryptamines: synthesis and pharmacological evaluation
      as 5-HT6 receptor ligands.
AB  - A series of N(1)-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N(1)-arylsulfonyl
      3-(4-chloro-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole derivatives (tryptamine
      derivatives with rigidized side chain) have been prepared and tested for their
      binding affinity to 5-HT(6) receptor. Several compounds displayed potent binding
      affinity for the 5-HT(6) receptor when tested in in vitro binding assay. The
      primary SAR indicates that rigidification of dimethylamino alkyl chain at C(3) of
      indole carbon maintains the binding affinity to 5-HT(6)R. The lead compound N(1)
      benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a
      (K(b)=0.1 nM) has shown excellent in vitro affinity and was active in animal
      models of cognition like NORT and water maze.

PMID- 21724393
TI  - Pharmacophore modeling and virtual screening to identify potential RET kinase
      inhibitors.
AB  - Chemical features based 3D pharmacophore model for REarranged during Transfection
      (RET) tyrosine kinase were developed by using a training set of 26 structurally
      diverse known RET inhibitors. The best pharmacophore hypothesis, which identified
      inhibitors with an associated correlation coefficient of 0.90 between their
      experimental and estimated anti-RET values, contained one hydrogen-bond acceptor,
      one hydrogen-bond donor, one hydrophobic, and one ring aromatic features. The
      model was further validated by a testing set, Fischer's randomization test, and
      goodness of hit (GH) test. We applied this pharmacophore model to screen NCI
      database for potential RET inhibitors. The hits were docked to RET with GOLD and
      CDOCKER after filtering by Lipinski's rules. Ultimately, 24 molecules were
      selected as potential RET inhibitors for further investigation.

PMID- 21724394
TI  - Cytotoxicity of aporphines in human colon cancer cell lines HCT-116 and Caco-2:
      an SAR study.
AB  - A series of synthetic aporphine derivatives structurally related to domesticine
      and nantenine (ring A, N6 and ring C truncated analogs), was evaluated in MTS
      cytotoxicity assays against the human colon cancer cell lines, HCT-116 and Caco
      2. In general, the C1 position of ring A is tolerant of alkoxy substituents as
      well as a benzoyl ester functionality. Other modifications evaluated resulted in
      a decrease in cytotoxic activity. The most potent compounds identified had IC(50)
      values in the range 23-38 MUM, comparable to the known cytotoxic agent,
      etoposide.

PMID- 21724395
TI  - New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with
      antileishmanial and antimalarial activities.
AB  - Continuing with our efforts to identify new active compounds against malaria and
      leishmaniasis, 14 new 3-amino-1,4-di-N-oxide quinoxaline-2-carbonitrile
      derivatives were synthesized and evaluated for their in vitro antimalarial and
      antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and
      Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies
      were carried out in order to analyze graphic SAR and ADME properties. The results
      obtained indicate that compounds with one halogenous group substituted in
      position 6 and 7 provide an efficient approach for further development of
      antimalarial and antileishmanial agents. In addition, interesting ADME properties
      were found.

PMID- 21724396
TI  - Serum matrix metalloproteinase-9 (MMP-9) as a biomarker for monitoring disease
      progression in Duchenne muscular dystrophy (DMD).
AB  - To identify serum biomarkers that allow monitoring of disease progression and
      treatment effects in Duchenne muscular dystrophy (DMD) patients, levels of matrix
      metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1)
      and osteopontin (OPN) were determined in 63 DMD patients on corticosteroid
      therapy. These proteins were selected for their role in the pathogenesis of
      muscular dystrophy. Levels of MMP-9 and TIMP-1 were significantly higher in sera
      of DMD patients compared to healthy controls, whereas the OPN levels showed no
      significant difference. MMP-9 levels were also observed to be significantly
      higher in older, nonambulant patients, compared to ambulant patients.
      Longitudinal data from a smaller cohort of DMD patients followed up for over
      4years showed that MMP-9, but not TIMP-1 increased significantly with age. Hence,
      MMP-9 is a potential DMD biomarker for disease progression. Future studies have
      to confirm whether serum MMP-9 levels can be used to monitor therapeutic
      response.

PMID- 21724397
TI  - Nemaline myopathy caused by mutations in the nebulin gene may present as a distal
      myopathy.
AB  - Mutations in the nebulin gene are the main cause of autosomal recessive nemaline
      myopathy, with clinical presentations ranging from mild to severe disease. We
      have previously reported a nonspecific distal myopathy caused by homozygous
      missense mutations in the nebulin gene in six Finnish patients from four
      different families. Here we describe three non-Finnish patients in two unrelated
      families with distal nemaline myopathy caused by four different compound
      heterozygous nebulin mutations, only one of which is a missense mutation. One of
      the mutations has previously been identified in one family with the severe form
      of nemaline myopathy. We conclude that nemaline myopathy and distal myopathy
      caused by nebulin mutations form a clinical and histological continuum. Nemaline
      myopathy should be considered as a differential diagnosis in patients presenting
      with an early-onset predominantly distal myopathy.

PMID- 21724398
TI  - The efficacy of antiepileptic drug prophylaxis in the prevention of early and
      late seizures following repair of intracranial aneurysms.
AB  - The efficacy of antiepileptic drug (AED) prophylaxis in patients undergoing
      aneurysm repair has been questioned, yet these drugs are routinely used in many
      institutions. To better define the relationship of AED prophylaxis to
      postoperative seizures, we undertook a review of 259 patients undergoing
      treatment for intracranial aneurysms. Incidence of late seizures was assessed by
      telephone interview in 132 patients (mean follow-up, 58.7 months). There were
      seven early seizures, all in patients who received AED prophylaxis (higher versus
      [vs.] no prophylaxis, p=0.019). There were 12 late seizures (nine with
      prophylaxis vs. three without prophylaxis, p=0.53). The timing of AED prophylaxis
      had no effect on the incidence of early or late seizures in either group. AED use
      was associated with an increased rate of early seizures. Postoperative seizures
      remain important adverse outcomes following aneurysm repair, but despite their
      traditional role, the routine use of AED should be reconsidered carefully.

PMID- 21724399
TI  - The neurologic manifestations of the acute porphyrias.
AB  - The porphyrias are diseases characterised by accumulation of porphyrins and
      porphyrin precursors owing to enzymatic deficiencies of the haem synthetic
      pathway. In the acute hepatic porphyrias accumulation of porphyrin precursors, in
      particular delta-aminolaevulinic acid (ALA), cause dysfunction of the central,
      peripheral and autonomic nervous systems. This leads to the characteristic
      clinical findings of abdominal pain, neuropsychiatric symptoms and neuropathy.
      The exact pathogenic mechanism is not clear but evidence to date suggests both
      direct toxic effects of ALA and intracellular metabolic derangement contribute to
      the neurologic disorders. This review explores the mechanisms of neural
      dysfunction in the acute porphyrias and the resultant clinical features of an
      acute attack.

PMID- 21724400
TI  - Spinal arachnoid cyst.
AB  - Preoperative, operative and postoperative radiological examinations and operative
      notes of 31 patients with spinal arachnoid cyst operated on during 2002-2009 at
      the Institute of Medical Sciences, Banaras Hindu University, were evaluated.
      Sixteen patients were male and 15 were female. All patients were managed
      surgically: extradural arachnoid cysts were managed by excision and intradural
      arachnoid cysts were managed by marsupialization. There was no recurrence in the
      4 years of follow up.

PMID- 21724401
TI  - Lymphoma as a cause of isolated oculomotor nerve palsy.
AB  - We report two patients with diffuse large B-cell lymphoma with isolated
      oculomotor nerve palsy. This was the initial manifestation of lymphoma in one
      patient but in a second, the palsy appeared as a part of a generalized recurrence
      of lymphoma. In addition, we reviewed the clinical findings of 12 previously
      reported patients. Isolated oculomotor nerve palsy was most frequently associated
      with the large B-cell lymphoma cell type, and was not frequently associated with
      periorbital pain. The pupil was spared in half the patients irrespective of
      infiltration of the oculomotor nerve. MRI and cerebrospinal fluid cytological
      examinations are helpful in determining invasion of lymphoma to the oculomotor
      nerve, cavernous sinus, and surrounding leptomeninges.

PMID- 21724402
TI  - The pathophysiological mechanisms underlying freezing of gait in Parkinson's
      Disease.
AB  - Freezing of gait is a paroxysmal phenomenon most commonly found in patients with
      advanced Parkinson's Disease. The pathophysiological mechanisms underlying this
      behaviour remain uncertain despite a well-characterised phenotype. Freezing
      behaviour extends beyond gait to affecting speech and upper limb function,
      suggesting that there is likely to be a universal mechanism underlying the
      phenomenon. This paper identifies the essential features required for a
      comprehensive model of freezing and evaluates a number of hypotheses that seek to
      explain the phenomenon. It appears likely that the pathophysiology of freezing
      involves context-dependant dysfunction across multiple levels of the neurological
      system, including cortical, subcortical and brainstem regions.

PMID- 21724403
TI  - Analogue-based design, synthesis and molecular docking analysis of 2,3-diaryl
      quinazolinones as non-ulcerogenic anti-inflammatory agents.
AB  - In our effort to identify potent gastric sparing anti-inflammatory agents, a
      series of methyl sulfanyl/methyl sulfonyl substituted 2,3-diaryl quinazolinones
      were designed by analogue-based design strategy and synthesized for biological
      evaluation. Subsequently, the compounds were evaluated for both cyclooxygenase
      inhibitions by ovine COX assay and carrageenan-induced rat paw edema assay. All
      the methyl sulfonyl substituted quinazolinones were exhibited promising anti
      inflammatory activity. In particular, 6-bromo-3-(4-methanesulfonyl-phenyl)-2
      phenyl-3H-quinazolin-4-one, 7-chloro-3-(4-methanesulfonyl-phenyl)-2-phenyl-3H
      quinazolin-4-one, 3-(4-methanesulfonyl-phenyl)-2-(4-methoxy-phenyl)-3H-quinazolin
      4-one and 6-bromo-3-(4-methanesulfonyl-phenyl)-2-(4-methoxy-phenyl)-3H-quinazolin
      4-one emerged as the most active compounds in the series. The results of
      ulcerogenic activity assay suggest that these compounds are gastric safe compared
      to indomethacin. The molecular docking analysis was performed to understand the
      binding interactions of these compounds to COX-2 enzyme. The results from the
      present investigation suggests that 2,3-diaryl quinazolinones as a promising
      template for the design of new gastric safe anti-inflammatory agents, which can
      be further explored for potential anti-inflammatory activity.

PMID- 21724404
TI  - Discovery of benzimidazole derivatives as novel multi-target EGFR, VEGFR-2 and
      PDGFR kinase inhibitors.
AB  - Multi-target EGFR, VEGFR-2 and PDGFR inhibitors are highly useful anticancer
      agents with improved therapeutic efficacies. In this work, we used two virtual
      screening methods, support vector machines (SVM) and molecular docking, to
      identify a novel series of benzimidazole derivatives, 2-aryl benzimidazole
      compounds, as multi-target EGFR, VEGFR-2 and PDGFR inhibitors. 2-Aryl
      benzimidazole compounds were synthesized and their biological activities against
      a tumor cell line HepG-2 and specific kinases were evaluated. Among these
      compounds, compounds 5a and 5e exhibited high cytotoxicity against HepG-2 cells
      with IC50 values at ~2 MUM. Further kinase assay study showed that compound 5a
      have good EGFR inhibitory activity and moderate VEGFR-2 and PDGFR inhibitory
      activities, while 5e have moderate EGFR inhibitory activity and slightly weaker
      VEGFR-2 and PDGFR inhibitory activities. Molecular docking analysis suggested
      that compound 5a more tightly interacts with EGFR and PDGFR than compound 5e. Our
      study discovered a novel series of benzimidazole derivatives as multi-target
      EGFR, VEGFR-2 and PDGFR kinases inhibitors.

PMID- 21724405
TI  - Atomic force microscopy of living and fixed Xenopus laevis embryos.
AB  - Xenopus laevis embryos are a rather simple and at the same time a very
      interesting animal model, which is widely used for research in developmental
      biology. Intensive coordinated cell movements take place during the multi
      cellular organism development. Little is known of the cellular, molecular and
      biomechanical mechanisms of these movements. The conceptual framework for
      analysis of cell interactions within integrated populations is poorly developed.
      We have used atomic force microscopy (AFM) to observe the surface of fixed X.
      laevis embryos at different stages of their development. We have developed a new
      sample preparation protocol for these observations. The obtained images were
      compared with scanning electronic microscopy (SEM) data. Cell rearrangement
      during morphogenesis in vivo was also visualized by AFM. In the current paper we
      discuss facilities and challenges of using this technique for further embryo
      researching.

PMID- 21724406
TI  - Cellular organisation of the mature testes and stages of spermiogenesis in Danio
      rerio (Cyprinidae; Teleostei)--structural and ultrastructural studies.
AB  - The male gonads of Danio rerio occupy a position typical of the Teleostei
      species. The structure of the testes corresponds to the anastomosing tubular type
      with unrestricted spermatogonia and represents a cystic type of spermatogenesis.
      The results of this study indicate that four distinct stages of cell
      differentiation can be identified during spermiogenesis. These stages are
      characterised by chromatin condensation, the development of flagellum, nuclear
      rotation, the formation of nuclear fossa and the elimination of excess cytoplasm.
      A round head and the absence of an acrosome characterise the differentiated
      sperm. The midpiece is short and large, and C-shaped mitochondria form a ring
      surrounding the initial region of the flagellum. The axoneme shows a 9+2 pattern.
      In the D. rerio spermatozoa the flagellar axis is at an angle of 110 degrees  to
      the nucleus diameter running through the centriole.

PMID- 21724407
TI  - Impact of reading pre-irradiation background signal on the post-irradiation glow
      curves of thermoluminescence dosimeters.
AB  - Due to their sensitivity, signal reproducibility and stability, lithium fluoride
      thermoluminescence dosimeters are widely used in many applications. It was
      noticed that post-irradiation glow curves of LiF dosimeters that had undergone
      pre-irradiation background dose measurements dramatically differed from the
      curves of dosimeters irradiated without such preliminary measurements. Three
      types of dosimeters were studied in this respect, namely, TLD-700, TLD-600, and
      TLD-100. Impact of pre-irradiation background measurements on the glow curve
      areas, peak positions, and individual peak intensities were investigated using
      computerized glow curve analysis. Similarities in the behavior of the dosimeters
      of all three types were found. Areas of the glow peaks P2a, P3, P4, P5, and P6
      increased. Peak P3 grew most significantly, followed by P2, and P5. Also, one of
      the common features was a shift of T(max) of P5 to higher temperatures. Pre
      irradiation background readings increase the total area of the glow curve in
      general and affect relative intensities and positions of specific peaks, which
      changes the shape of the glow curve. It is strongly recommended to perform pre
      irradiation background measurements for all LiF-based dosimeters regardless of
      the values of the background doses relative to the radiation doses to be given.

PMID- 21724408
TI  - Effects of autogenous growth factors on heterotopic bone formation of osteogenic
      cells in small animal model.
AB  - AIMS: This study used a new approach to investigate the effective concentrations
      of growth factors released from platelet concentrate (PC) on the bone formation
      capacity of osteogenically differentiated rat bone marrow stromal cells (rBMSCs).
      MATERIALS AND METHODS: Rat BMSCs and whole blood were harvested from 40 adult
      male Spraque-Dawly rats. Rat BMSCs were expanded in an osteogenic medium and
      seeded on inert collagenous bovine bone matrix (ICBM). Growth factors released
      from degranulated PC (GFs) containing TGF-beta1 1 (25ng/ml)-10ng (250ng/ml) and
      rhBMP-2 400ng (10MUg/ml) were suspended in 40MUl platelet poor plasma (PPP) and
      applied on the ICBM-rBMSC constructs or ICBM only, respectively. The constructs
      were then transplanted in autologous hosts for 4 weeks. Concurrently,
      osteoblastic differentiation of rBMSCs on ICBM-rBMSC-PPP constructs was
      characterized in vitro. RESULTS: Rat BMSCs in osteogenic medium exhibited
      phenotypes of mature osteoblasts. The amount of newly formed bone among groups of
      ICBM-rBMSC-PPP with and without GFs was not significantly different (p>0.05) and
      was significantly lower than a group of ICBM-PPP-BMP-2 (p<0.05). CONCLUSIONS:
      Autogenous GFs had no effect on the capacity of rBMSCs to form new bone. The
      ability to measure the bone formation capacity of transplanted autologous cells
      and growth factors in a small animal model was demonstrated.

PMID- 21724409
TI  - Trigonocephaly: results after surgical correction of nonsyndromatic isolated
      metopic suture synostosis in 54 cases.
AB  - Children with nonsyndromatic isolated metopic suture synostosis suffer from a
      significant deformity of the supraorbital ridges, the temporal regions and
      hypotelorism. We retrospectively analyzed 54 consecutive cases of isolated
      nonsyndromatic metopic synostosis treated over a 14-year-period. The data were
      evaluated using patients' clinical records, skull radiographs in two planes, CT
      scans, MRI scans and pre-/post-operative photographs. Surgery with standardized
      fronto-orbital advancement was performed at a median age of 11.5 months. Follow
      up ranged from 4.5 months to 177.4 months, with an average of 51.9 months. The
      average blood loss was less than 255ml and the average post-operative length of
      stay was 5 days. Not a single major complication was observed except for
      uncomplicated dural tears in six cases. According to the classification of
      Whitaker, results were considered good to excellent (Category I and II) in all
      except one case (Category IV). As the current techniques have been standardized
      for routine use, surgical risks are reasonably low with no mortality or permanent
      morbidity. We think that the treatment of single metopic synostosis is safe with
      very low reoperation rates and short length of hospital stay. Overall, our
      results showed acceptable minor complication rates and generally satisfactory
      aesthetic outcomes.

PMID- 21724410
TI  - Tissular T(regs): a unique population of adipose-tissue-resident Foxp3+CD4+ T
      cells that impacts organismal metabolism.
AB  - Foxp3+CD4+ regulatory T (T(reg)) cells are a key population in controlling the
      immune response. Recently, their roles have been expanded to broader, non-immune,
      contexts, in particular the metabolic consequences downstream of obesity-induced
      inflammation, e.g. type-2 diabetes and cardiovascular disease. This review
      highlights the major innate and adaptive immune cell subsets contributing to
      adipose-tissue inflammation, the key role played by fat-resident T(regs), and the
      potential of T(reg)-based therapies for treatment of the metabolic syndrome.

PMID- 21724412
TI  - Contraceptive changes after reproductive events among Australian women born in
      1973 to 1978: a longitudinal study from 1996 to 2009.
AB  - BACKGROUND: Women change contraception as they try to conceive, space births, and
      limit family size. This longitudinal analysis examines contraception changes
      after reproductive events such as birth, miscarriage or termination among
      Australian women born from 1973 to 1978 to identify potential opportunities to
      increase the effectiveness of contraceptive information and service provision.
      METHODS: Between 1996 and 2009, 5,631 Australian women randomly sampled from the
      Australian universal health insurance (Medicare) database completed five self
      report postal surveys. Three longitudinal logistic regression models were used to
      assess the associations between reproductive events (birth only, birth and
      miscarriage, miscarriage only, termination only, other multiple events, and no
      new event) and subsequent changes in contraceptive use (start using, stop using,
      switch method) compared with women who continued to use the same method. RESULTS:
      After women experienced only a birth, or a birth and a miscarriage, they were
      more likely to start using contraception. Women who experienced miscarriages were
      more likely to stop using contraception. Women who experienced terminations were
      more likely to switch methods. There was a significant interaction between
      reproductive events and time indicating more changes in contraceptive use as
      women reach their mid-30s. CONCLUSION: Contraceptive use increases after the
      birth of a child, but decreases after miscarriage indicating the intention for
      family formation and spacing between children. Switching contraceptive methods
      after termination suggests these pregnancies were unintended and possibly due to
      contraceptive failure. Women's contact with health professionals around the time
      of reproductive events provides an opportunity to provide contraceptive services.

PMID- 21724411
TI  - Extra-thymically induced regulatory T cells: do they have potential in disease
      prevention?
AB  - Fopx3(+) Treg safeguard against autoimmune diseases and immune pathology. The
      extrathymic conversion of naive T cells into Foxp3(+) regulatory T cells can be
      achieved in vivo by the delivery of strong-agonist ligands under subimmunogenic
      conditions. Tolerogenic vaccination with strong-agonist mimetopes of self-antigen
      to promote self-antigen specific tolerance may represent the most specific and
      safest means of preventing autoimmunity. This review discusses the requirements
      for induction of dominant tolerance exerted by Foxp3(+) Tregs in autoimmunity
      with special emphasis on their impact to interfere with T1D. The future goals are
      the understanding of self-non-self discrimination at the cellular and molecular
      level, which should then enable investigators to develop clinical vaccination
      protocols that specifically interfere with unwanted immune responses.

PMID- 21724413
TI  - Violence against women from different relationship contexts and health care
      utilization in Spain.
AB  - BACKGROUND: Studies reported an excess of health services utilization among women
      with violence by an intimate partner (IPV). However, little is known about health
      utilization by women victims of other forms of interpersonal violence than IPV.
      This study aimed to determine the effect of violence from different relationship
      contexts on health care utilization. METHODS: A cross-sectional study following a
      multistage cluster sampling scheme was conducted. Women aged 18 to 70 years were
      randomly selected according to their scheduled health care visit. The number of
      women invited to participate was 16,419 and 73% accepted. After exclusion, the
      final sample consisted of 10,815 women. The outcome variables were health care
      utilization (primary care, specialty services, emergency rooms, and hospital
      admissions) and the predictor variable was interpersonal violence from different
      relationship contexts. Multivariable adjusted logistic regression models were
      conducted to assess the independent effect of each violence relationship context
      on health care utilization. MAIN FINDINGS: Compared with never abused women, use
      of health services was significantly higher for abused women, although the rates
      varied depending on the violence relationship context. The greatest probability
      of service use was among women whose abuse was perpetrated by both a partner and
      others. Comparing the magnitude of effect of each violence category by
      perpetrators other than a partner, this effect was stronger for violence in a
      social context in the case of emergency rooms only. CONCLUSION: Regardless of the
      perpetrator, lifetime violence increased health services utilization. Violence
      affects women's behavior in terms of how they use health services.

PMID- 21724414
TI  - The National Institutes of Health commitment to research on women and girls and
      AIDS.

PMID- 21724415
TI  - Anesthetic management of patients undergoing aortic valve bypass (apicoaortic
      conduit) surgery.

PMID- 21724416
TI  - Prone ventilation in the management of infants with acute respiratory distress
      syndrome after complex cardiac surgery.

PMID- 21724417
TI  - The management and outcome of documented intraoperative heart rate-related
      electrocardiographic changes.
AB  - OBJECTIVES: The authors analyzed surgical cases in which electrocardiographic
      (ECG) signs of cardiac ischemia were noted to be precipitated by increases in
      heart rate (ie, heart rate-related ECG changes [REC]). The authors aimed to find
      REC incidence, specificity for coronary artery disease (CAD), and the outcome
      associated with different management strategies. DESIGN: A retrospective review.
      SETTING: A university hospital, tertiary care. PARTICIPANTS: Patients undergoing
      surgery under anesthesia. INTERVENTIONS: A chart review. MEASUREMENTS: The
      authors searched 158,252 anesthesia electronic records for comments noting REC
      (ie, ST-segment or T-wave changes). After excluding cases with potentially
      confounding conditions (eg, hypotension, hyperkalemia, and so on), 26 cases were
      analyzed. RESULTS: REC commonly was precipitated by anesthesia-related events
      (ie, intubation, extubation, and treatment of bradycardia). In 24 cases, REC was
      managed by prompt heart rate reduction using beta-blocker agents, opioids, and/or
      cardioversion in the addition to the removal of stimulus. Only 1 case had a copy
      of the ECG printed. Two cases were aborted, 1 was shortened and 23 proceeded
      without change. Postoperative troponin T levels were checked, and cardiology
      consultation was obtained in selected cases and led to further cardiac evaluation
      in 6 cases. Postoperative myocardial infarction developed in only 1 patient in
      whom the ECG changes were allowed to persist throughout the case. CONCLUSIONS:
      This incidence of reported REC was much lower than the previously reported
      incidence of ischemia-related ECG changes, suggesting that the largest proportion
      of events go unnoticed. In many patients, subsequent cardiology workup did not
      confirm the existence of clinically significant CAD.

PMID- 21724418
TI  - Adherence to immunosuppression in adult lung transplant recipients: prevalence
      and risk factors.
AB  - BACKGROUND: Adherence to medication is a favourable with regard to survival after
      kidney, heart and liver transplantation. Little is known about adherence to
      medication in lung transplant recipients. To determine the prevalence of
      adherence and identify risk factors of non-adherence (NA) we evaluated adherence
      to tacrolimus in adult lung transplant recipients who were at least 1 year after
      transplantation. METHODS: Tacrolimus intake was prospectively monitored using the
      Medication Event Monitoring System (MEMS). Recipients qualified as adherent if a
      timing-adherence score of >= 80% was reached. Patients' characteristics and
      possible risk factors for NA were collected using the Karnofsky Performance
      Index, Self-Care Agency ASA Scale, State-Trait Anxiety Inventory, Zung Self
      Rating Depression Scale, and the Long-Term Medication Behavior Self-Efficacy
      Scale. RESULTS: Ninety-one recipients used MEMS for a median of 95 days (range 50
      to 124 days) and were included. They showed a median timing-adherence score of
      98.1% (range 31.2% to 100%). A timing-adherence score of >= 80% was seen in 92.3%
      of the recipients. Multiple logistic regression showed an association of lower
      timing-adherence scores with younger age and lower ability of self-care.
      CONCLUSIONS: Adherence to immunosuppressive therapy was very high in lung
      transplant recipients. Only 7.7% of the recipients were non-adherent. Younger
      recipients and recipients with lower ability of self-care appeared to be at risk
      for NA. Follow-up of clinical data is needed to determine whether NA is
      associated with poorer outcome, specifically bronchiolitis obliterans syndrome.

PMID- 21724419
TI  - Polyethylene wear in retrieved reverse total shoulder components.
AB  - BACKGROUND: Reverse total shoulder arthroplasty has been used to treat rotator
      cuff tear arthropathy and proximal humerus fractures, as well as for failed
      conventional total shoulder prostheses. It has been suggested that polyethylene
      wear is potentially higher in reverse shoulder replacements than in conventional
      shoulder replacements. The modes and degree of polyethylene wear have not been
      completely elucidated. The purpose of this study was to evaluate polyethylene
      wear patterns in 7 specimens retrieved at revision arthroplasty and identify
      factors that may be associated with increased wear. METHODS: Reverse total
      shoulder components were retrieved from 7 patients during revision arthroplasty
      for loosening and/or pain. Preoperative glenoid tilt and placement and scapular
      notching were evaluated by use of preoperative radiographs. Polyethylene wear was
      evaluated via micro-computed tomography and optical microscopy. RESULTS: Wear on
      the rim of the polyethylene humeral cup was identified on all retrieved
      components. The extent of rim wear varied from a penetration depth of 0.1 to 4.7
      mm. We could not show a correlation between scapular notching and rim wear.
      However, rim wear was more extensive when the inferior screw had made contact
      with the liner. Metal-on-metal wear between the humeral component and the
      inferior screw of 1 component was also observed. Wear of the intended bearing
      surface was minimal. DISCUSSION: Rim damage was the predominant cause of
      polyethylene wear in our retrieved specimens. Direct contact between the humeral
      component and inferior metaglene screws is concerning because this could lead to
      accelerated ultra-highmolecular weight polyethylene wear and also induce
      mechanical loosening of the glenoid component.

PMID- 21724420
TI  - A pedicled bone graft from the acromion: an anatomical investigation regarding
      surgical feasibility.
AB  - OBJECTIVE: To investigate the technical feasibility of harvesting a vascularized
      bone graft from the acromion pedicled on the acromial branch. BACKGROUND: Complex
      fractures of the proximal humerus may result in partial or total avascular
      necrosis of the head fragment. Treatment of avascular necrosis of the humeral
      head is dependent upon the stage of disease as well as the dimension and location
      of necrosis. In general, the outcome is poor and complete restoration of the
      shoulder function is rarely attained. Contrary to osteonecrosis of carpal bones
      (where vascularized bone grafts have been routinely carried out for decades),
      reports of analogous procedures at the humeral head are anecdotal. METHODS: Based
      on selective post-mortem computer-tomographic angiography of 5 and the dissection
      of 30 embalmed human cadaver shoulders, we describe the anatomy of the acromial
      branch of the thoracoacromial trunk. The main focus was the constancy of its
      anatomical course, its dimensions and potential use as a nutrient vessel for a
      pedicled bone graft from the acromion. RESULTS: The course of the acromial branch
      revealed a constant topographic relationship to anatomical landmarks. Its
      terminal branches reliably supplied the anterior part of the acromion. The
      vascularized bone graft could be sufficiently mobilized to allow tension-free
      transfer to the humeral head as well as to the lateral two-thirds of the
      clavicle. CONCLUSION: We demonstrated the feasibility of vascularized bone graft
      harvesting from the acromion. This technique could be a joint-preserving
      procedure for osteonecrosis of the humeral head or may assist in the revision of
      a clavicular pseudoarthrosis.

PMID- 21724421
TI  - A cross-sectional study of demographic and morphologic features of rotator cuff
      disease in paraplegic patients.
AB  - BACKGROUND: This study analyzed the demographic and morphologic features of
      rotator cuff disease in paraplegic patients who presented with or without
      shoulder pain. METHODS: Clinical and magnetic resonance imaging examinations of
      both shoulders were performed in 317 paraplegic patients. Mean age was 49 (range,
      19-76) years. The level of spinal cord injury was between T2 and T7 In 54% of
      patients and between T8 and L3 in 46%. Constant scores were measured for all
      shoulders. Pain was analyzed using a visual analog scale. RESULTS: Rotator cuff
      tears were not present in 51%, were unilateral in 20%, and were bilateral in 29%.
      Age was older and duration of spinal cord injury was significantly longer in
      patients with bilateral tears than in patients without or with unilateral tears
      (P < .001). In patients with unilateral tears, a full-thickness rupture of the
      supraspinatus tendon was found in 67%, whereas a partial-rupture was detected in
      33%. Of the patients with bilateral tears, 75% presented with a full-thickness
      rupture and 25% with a partial rupture. The mean Constant score was 76 (range, 37
      98) in patients without cuff tears, 69 (range, 16-94) for patients with
      unilateral tears, and 64 (16-96) for patients with bilateral tears (P < .001).
      CONCLUSIONS: Rotator cuff disease is common and correlates highly with age and
      duration of spinal cord injury, which underlines the theory of "wear and tear" in
      wheelchair-dependent patients.

PMID- 21724422
TI  - Radial head translation measurement in healthy individuals: the radiocapitellar
      ratio.
AB  - HYPOTHESIS: We hypothesized that the radiocapitellar ratio (RCR) is a valid and
      reproducible method to assess radial head translation in healthy individuals and
      that the normal RCR of healthy individuals is 0%. MATERIALS AND METHODS: Lateral
      radiographs of the elbow were examined in 40 healthy patients. The measurement
      method of the RCR was the displacement of the radial head (minimal distance
      between the right bisector of the radial head and the center of the capitellum)
      divided by the diameter of the capitellum. Intraobserver and interobserver
      reliability was evaluated using intraclass correlation (ICC). RESULTS: The RCR
      was 4% +/- 4% (range, -7% to 19%). The mean RCR of 4% measured in this cohort
      represents an anterior displacement of 1 mm in a capitellum of 25 mm.
      Intraobserver reliability was good (ICC, 0.72) and interobserver reliability was
      fair (ICC, 0.52). A significant side-to-side correlation was observed (r = 0.4, P
      = .009). No difference was identified between men and women, and no correlation
      was identified between age and the RCR. The standard deviation of the centered
      RCR measurements was 3%, which represented the variability of RCR measurements.
      CONCLUSIONS: The results of this study confirm the traditional belief that in the
      normal elbow, the radial head is generally aligned towards the capitellum on
      lateral radiographs. Accordingly, a RCR observed outside the ranges of 1 mm
      posterior (-5%) to 3 mm anterior (13%) in a 25 mm capitellum suggests a
      misalignment at the RC joint of the elbow. The RCR method to assess RC joint
      translations has demonstrated a normal distribution in healthy individuals and
      good reliability.

PMID- 21724423
TI  - Oral ketamine controlled refractory nonconvulsive status epilepticus in an
      elderly patient.
AB  - Nonconvulsive status epilepticus (NCSE) is a heterogeneous disorder with
      different seizure types and diverse etiologies, and is mainly characterized by
      altered consciousness. The recognition of NCSE is more challenging than
      generalized convulsive SE, and diagnosis and treatment are often delayed.
      Therefore, some cases can evolve into refractory SE and become pharmacoresistant
      even with GABAergic anesthetics. Herein we report the successful clinical
      experience of pharmacoresistant complex partial SE treated with ketamine. An
      elderly woman was profoundly stuporous and had relentless clonic movements of the
      right hand and forearm. Electroencephalography revealed repetitive periodic
      lateralized epileptiform discharges (PLEDs). There was a poor clinical response
      to standard anticonvulsants and GABAergic anesthetics. Both the clinical and
      electroencephalographic SE were controlled after intravenous ketamine therapy.
      Rebound refractory NCSE occurred about six days after discontinuing the
      intravenous ketamine, which was successfully terminated by oral ketamine
      treatment. There were no adverse effects observed.

PMID- 21724424
TI  - Speech preservation using a non-linear paradigm for determination of the extent
      of neocortical resection in patients with mesial temporal sclerosis submitted to
      cortico-amygdalo-hippocampectomy (CAH).
AB  - RATIONALE: The rationale for using a non-linear (proportional) paradigm for
      determining the extent of the neocortex to be removed in temporal lobe resection
      was based on anatomical and intra-operative cortical mapping findings. We present
      our results regarding speech preservation in patients submitted to CAH using the
      central artery as an anatomical landmark for determining the posterior border of
      neocortical resection. METHODS: Two hundred and fifty consecutive right-handed
      patients with left unilateral mesial sclerosis were studied. All patients were
      submitted to CAH under general anesthesia and without intraoperative
      electrocorticography. The posterior border of the lateral neocortical resection
      was defined by a line perpendicular to the temporal axis at the level of the
      central artery. RESULTS: Seven patients had transient (1-3 weeks; mean=9 days)
      receptive speech disturbance. There was no permanent speech deficit. Imaging
      documented edema or contusion at the posterior temporal cortical border in all
      patients who had transient speech deficits. The mean extent of cortical resection
      was 3.9 cm in adults and 3.1cm in kids. DISCUSSION: This is the first report in
      the literature discussing the use of a non-linear paradigm to determine the
      extent of lateral neocortical removal in this patient population. We found no
      permanent speech disturbances in this series. The non-linear approach used in
      this series proved to be safe and effective to avoid post-operative speech
      disorders. It was able to compensate for different brain and head sizes, and
      allowed smaller neocortical removal when compared to traditional linear
      approaches.

PMID- 21724425
TI  - Use of expanded reverse sural artery flap in lower extremity reconstruction.
AB  - Coverage of defects of the distal third portion of the leg and foot remains a
      challenge for surgeons. The difficulty results from the limited mobility and
      availability of the overlying skin, the weight-bearing requirements, and the
      relatively poor circulation of the skin. From January 2008 to December 2009, 10
      patients had defects of the foot and ankle covered using the 2-stage expanded
      reverse sural flap. Of these 10 patients, 6 had at least 1 risk factor for
      compromised wound healing, such as diabetes mellitus, peripheral arterial
      disease, venous insufficiency, tobacco smoking, or age older than 40 years. Flap
      necrosis was observed in only 1 patient (10%). Venous congestion was noted in 2
      patients (20%) by the third postoperative day, 1 of whom responded to postural
      elevation of the extremity and 1 to medicinal leech therapy. Although it is a 2
      stage procedure that requires wound dressing during the expansion, we strongly
      suggest the use of the expanded reverse sural flap for defects too large to be
      primarily closed, especially in patients older than 40 years with risk factors
      such as diabetes mellitus, peripheral arterial disease, or venous insufficiency.

PMID- 21724427
TI  - Accuracy, reproducibility and repeatability of ultrasonography in the assessment
      of abdominal adiposity.
AB  - RATIONALE AND OBJECTIVES: Despite improvements in the methods used in body
      composition analysis, some goals remain far from clinical practice. Among them,
      the most important is the quantification of intra-abdominal adipose tissue. Fat
      distribution is a key point in the assessment of cardiovascular and metabolic
      risk status. The aim of this study was to define the accuracy, reproducibility,
      and repeatability of ultrasonography in the evaluation of abdominal adiposity.
      MATERIALS AND METHODS: Twenty-six nonobese patients (group A) who underwent
      computed tomographic (CT) abdominal imaging and 29 obese patients (group B) were
      enrolled. Patients from both groups were independently evaluated using ultrasound
      by three radiologists; computed tomography-like conditions were reproduced, and
      six main parameters of subcutaneous and internal adiposity were measured (as well
      as three derived indexes) with both linear and convex probes. In group A, the
      same measurements were also obtained on CT images. Time spent for every
      ultrasound session was recorded. Results were analyzed using Lin's concordance
      correlation (rho), intraclass correlation, and linear regression analysis (and
      analysis of variance). RESULTS: Three patients were excluded from group A after
      CT scans because of technical problems. Mesenteric fat thickness did not show
      significant correlations and reliability. Strong correlations between ultrasound
      and CT measurements were observed for all other visceral and subcutaneous
      parameters (rho = 0.85-0.96). Intraobserver and interobserver agreement was
      excellent in both groups (repeatability: rho = 0.83-0.99 for group A, rho = 0.90
      0.99 for group B; reproducibility: intraclass correlation coefficient = 0.90-0.99
      for groups A and B). The mean time spent was 95 +/- 21 seconds for group A (mean
      body mass index, 27.4 +/- 2.4 kg/m(2)) and 129 +/- 33 seconds for group B (mean
      body mass index, 37.3 +/- 11.9 kg/m(2)). CONCLUSIONS: Ultrasound is accurate,
      reproducible, and fast in the analysis of abdominal adiposity. It offers a
      regional, easy, and close-at-hand evaluation of subcutaneous and visceral fat
      compartments. This should be taken into consideration when clinical routine
      examinations are performed or to evaluate patients with specific metabolic
      diseases before and after treatment.

PMID- 21724428
TI  - Effect of chronic transfusion therapy on progression of neurovascular pathology
      in pediatric patients with sickle cell anemia.
AB  - BACKGROUND: Chronic blood transfusion (CBT) is currently the standard of care for
      primary and secondary stroke prevention in children with sickle cell anemia
      (SCA). However, the effect of CBT on cerebrovascular pathology is not well known.
      METHODS: We reviewed children with SCA receiving CBT for abnormal transcranial
      Doppler (TCD) [n=12] or cerebrovascular accident (CVA) [n=22]. Baseline cerebral
      magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) were
      compared with the most recent scans available for each patient and independently
      scored by a neuroradiologist. RESULTS: Thirty-four patients with a mean age of
      6.5years at the time of baseline MRI/MRA were studied. Average elapsed time from
      baseline to most recent scans was 7.3years. Overall, patients experienced
      worsening vasculopathy, as measured by mean increases in their baseline MRI and
      MRA scores of +0.76 and +1.03. There was a significant difference in the mean
      change of MRI/MRA scores between patients who had CVA and abnormal TCD (MRI;
      +1.23 vs. -0.08, p=0.001 and MRA; +1.54 vs. +0.08, p=0.02). Patients with
      abnormal baseline MRA had worsening scores compared to those with normal baseline
      MRA (54% vs. 9.5%, p=0.01). Also, patients who had CVA were more likely to have
      an abnormal baseline MRA and worsening scores compared to abnormal TCD patients.
      CONCLUSION: We show that children with CVA experience progression of cerebral
      vasculopathy despite CBT. In contrast, CBT for abnormal TCD confers protection
      against the development and/or progression of cerebral vasculopathy. This effect
      appears to be real given our large cohort of patients with longer follow up as
      compared to previous studies.

PMID- 21724429
TI  - Clinicopathologic analysis of the impact of CD23 expression in plasma cell
      myeloma with t(11;14)(q13;q32).
AB  - A recent study has shown that 10% of plasma cell myelomas (PCMs) express CD23 and
      that expression is associated with abnormalities of chromosome 11, mainly
      t(11;14)(q13;q32); however, only 40% of t(11;14)(+) PCMs express CD23. Because
      these results were generated in a limited patient cohort and because the clinical
      relevance of CD23 expression in PCMs with t(11;14)(q13;q32) has not been fully
      characterized, we addressed this question in a large series of patients with
      t(11;14)(+) PCM. Forty-two bone marrow biopsies from patients with t(11;14)(+)
      PCM were evaluated for CD23 expression by immunohistochemistry. CD23 expression
      was correlated with laboratory and clinical data and outcome after autologous
      stem cell transplantation, including event-free survival and overall survival
      (OS). Plasma cell myelomas with t(11;14)(q13;q32) were frequently CD20(+) (46.4%)
      and CD56(-) (53.8%) and had a nonhyperdiploid karyotype (97.6%) with frequent 13q
      deletion (33.3%). Of 42 cases, 19 (45.2%) expressed CD23. CD23(+) PCMs were more
      likely to present with platelet counts less than 150 * 10(3)/MUL (100% vs 50%, P
      = .006). There were no significant differences in other laboratory or presenting
      clinical data. The median event-free survival in patients treated with autologous
      stem cell transplantation (n = 29) was similar regardless of CD23 status, whereas
      the median OS (all patients) was longer in CD23(-) than in CD23(+) PCMs: not
      reached vs 3365 days (P = .08). Our findings suggest that patients with
      t(11;14)(+)/CD23(+) PCM present with lower platelet counts and may have a shorter
      OS than those with t(11;14)(+)/CD23(-) PCM.

PMID- 21724430
TI  - Adenocarcinoma arising in an ectopic mediastinal pancreas.
AB  - Pancreatic ectopia in the mediastinum is rare, and there are no reports that it
      has ever given rise to malignancy. Here we report a case of adenocarcinoma
      arising in ectopic pancreatic tissue in the mediastinum of a 66-year-old woman.
      The tumor arose in a partially cystic and partially solid ectopic pancreas
      containing both exocrine and endocrine components. Thorough clinical examination
      and clinical follow-up did not reveal other primary sites. The tumor was
      partially resected but metastasized to the anterior sternum 6 months later and
      was re-excised. No other similar cases of primary mediastinal pancreatic
      adenocarcinoma are on record in medical literature.

PMID- 21724431
TI  - Hemophagocytic lymphohistiocytosis associated with influenza A (H1N1) infection
      in a patient with chronic lymphocytic leukemia: an autopsy case report and review
      of the literature.
AB  - H1N1 influenza A virus can trigger fatal hemophagocytic lymphohistiocytosis in
      immunocompromised patients and in immunocompetent hosts, usually children. We
      present a case of a 50-year-old man with low-burden chronic lymphocytic leukemia
      who had sudden reactivation of his leukemia triggered by influenza A (H1N1)
      infection with hemophagocytic lymphohistiocytosis during the 2009 H1N1 pandemic.
      His rapid course was complicated by acute respiratory distress syndrome with
      diffuse alveolar damage, a 6-fold rise in lymphocyte count, disseminated
      intravascular coagulation, and, ultimately, cardiac arrest. Major findings at
      autopsy included: bilateral H1N1 pneumonitis with diffuse alveolar damage, intra
      alveolar pulmonary hemorrhage, pulmonary microthromboemboli, pulmonary
      hemorrhagic infarction, hemophagocytic lymphohistiocytosis in multiple locations,
      and diffuse chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis is a
      serious and often fatal condition, which may be primary or secondary. It may be
      associated with high-grade lymphoproliferative malignancies, especially in
      patients with therapy-related leukocytopenia, but only rarely is it seen in
      uncomplicated chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis
      may be triggered by a variety of infections (viral, fungal, bacterial and
      parasitic), but H1N1 influenza A-associated hemophagocytic lymphohistiocytosis is
      often rapidly fatal, especially in children. This adult patient's clinical
      presentation with low tumor burden and leukocytosis is thus unique. We review the
      recently published autopsy findings in fatal influenza A (H1N1) infection and the
      association with resultant secondary hemophagocytic lymphohistiocytosis.

PMID- 21724432
TI  - Proximal-type epithelioid sarcoma of the vulva with INI1 diagnostic utility.
AB  - Proximal epithelioid sarcoma (PES) is an extremely uncommon neoplasm of the vulva
      with an aggressive behavior. Recently, these authors experienced a case of
      proximal-type ES in a 41-year-old woman who was admitted for a rapidly growing
      mass in the right mons pubis. An about-1-cm-sized mass was initially noticed one
      and a half years earlier. The excised mass, however, was 8 cm in greatest
      dimension and was relatively well circumscribed. The cut surface was
      trabeculated, with multifocal hemorrhages and necroses. Microscopically, the
      tumor consisted of epithelioid rhabdoid cells with vesicular nuclei, large
      prominent nucleoli, and cytoplasmic eosinophilic globules comparted by thin,
      fibrous septae. The main differential diagnoses included PES, other sarcomas with
      epithelioid cells, malignant melanoma, and sarcomatoid carcinoma. The tumor cells
      were diffusely positive for vimentin and EMA; focally positive for cytokeratin;
      and negative for CK5/6, CD34, S-100 protein, desmin, and myogenin. INI1
      (hSNF5/SMARCB1, a member of the SW1/SNF chromatin remodeling complex located on
      chromosome 22q11.2) staining clearly showed loss of expression in the tumor
      cells. Recent studies reported that some ESs also showed INI1 inactivation, as
      characteristically seen in malignant rhabdoid tumors of infancy. Reported herein
      is the diagnostic utility of INI-1 on PES and the possible relationship between
      PES and malignant rhabdoid tumor of the soft tissue, besides a collective review
      of the reported cases of PES of the vulva and of the current case.

PMID- 21724433
TI  - Pleomorphic hyalinizing angiectatic tumor of renal hilum.
AB  - Pleomorphic hyalinizing angiectatic tumor (PHAT) is a recently described rare
      entity. The tumor histogenesis is proposed to be of primitive undifferentiated
      mesenchyme. The tumor has a predilection for the subcutaneous soft tissue
      especially of lower extremity, although other locations have been well
      documented. We report a case of PHAT arising in the hilum of the kidney,
      clinically mimicking an infiltrating malignant neoplasm of renal pelvis. The
      tumor was discovered during workup for unrelated gastrointestinal tract symptoms.
      Because of the location of the lesion, excision of mass and radical nephrectomy
      were performed. The tumor had strong immunohistochemical expression of vimentin,
      CD34, CD99, and vascular endothelial growth factor (VEGF). No additional lesions
      were documented during 3 years of follow-up. This is consistent with the current
      thinking that PHAT is a benign neoplasm with increased incidence of recurrence.
      We document the unique retroperitoneal location of this rare tumor and suggest
      that PHAT should be considered among the list of unusual lesions at this site.

PMID- 21724434
TI  - Simulation of urea-induced protein unfolding: a lesson from bovine beta
      lactoglobulin.
AB  - To investigate the molecular mechanisms involved in the very initial stages of
      protein unfolding, we carried out one long (1 MUs) simulation of bovine beta
      lactoglobulin (BLG) together with three (500 ns) supporting MD runs, in which the
      unfolding conditions were produced by adding the osmolyte urea to the simulated
      systems and/or by increasing the thermal energy raising the temperature from 300
      to 350 K. BLG was chosen, since it is a well-characterized model protein, for
      which structural and folding properties have been widely investigated by X-ray
      and NMR. MD trajectories were analyzed not only in terms of standard progress
      variables, such as backbone H-bonds, gyration radius width, secondary structure
      elements, but also through the scrutiny of interactions and dynamical behavior of
      specific key residues previously pointed out and investigated by NMR and
      belonging to a well known hydrophobic cluster. MD trajectories simulated in
      different unfolding conditions suggest that urea destabilizes BLG structure
      weakening protein::protein hydrophobic interactions and the hydrogen bond
      network. The early unfolding events, better observed at higher temperature,
      affect both secondary and tertiary structure of the protein.

PMID- 21724435
TI  - Correlations between trabecular bone score, measured using anteroposterior dual
      energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone
      microarchitecture: an experimental study on human cadaver vertebrae.
AB  - Developing a novel technique for the efficient, noninvasive clinical evaluation
      of bone microarchitecture remains both crucial and challenging. The trabecular
      bone score (TBS) is a new gray-level texture measurement that is applicable to
      dual-energy X-ray absorptiometry (DXA) images. Significant correlations between
      TBS and standard 3-dimensional (3D) parameters of bone microarchitecture have
      been obtained using a numerical simulation approach. The main objective of this
      study was to empirically evaluate such correlations in anteroposterior spine DXA
      images. Thirty dried human cadaver vertebrae were evaluated. Micro-computed
      tomography acquisitions of the bone pieces were obtained at an isotropic
      resolution of 93MUm. Standard parameters of bone microarchitecture were evaluated
      in a defined region within the vertebral body, excluding cortical bone. The bone
      pieces were measured on a Prodigy DXA system (GE Medical-Lunar, Madison, WI),
      using a custom-made positioning device and experimental setup. Significant
      correlations were detected between TBS and 3D parameters of bone
      microarchitecture, mostly independent of any correlation between TBS and bone
      mineral density (BMD). The greatest correlation was between TBS and connectivity
      density, with TBS explaining roughly 67.2% of the variance. Based on multivariate
      linear regression modeling, we have established a model to allow for the
      interpretation of the relationship between TBS and 3D bone microarchitecture
      parameters. This model indicates that TBS adds greater value and power of
      differentiation between samples with similar BMDs but different bone
      microarchitectures. It has been shown that it is possible to estimate bone
      microarchitecture status derived from DXA imaging using TBS.

PMID- 21724436
TI  - Higher apoptotic state in Fabry disease peripheral blood mononuclear cells.:
      effect of globotriaosylceramide.
AB  - Fabry disease is an X-linked lysosomal storage disorder (LSD) due to deficiency
      of the enzyme alpha-galactosidase A, resulting in intracellular deposition of
      globotriaosylceramide (Gb3). Accumulation of Gb3 is probably related to tissue
      and organ dysfunctions. Diverse pathological mechanisms are elicited in LSDs,
      giving together the phenotypic expression of each disease. The purpose of the
      present study is to investigate if apoptosis could play a role in Fabry disease
      pathogenesis and to understand the mechanisms involved in the proapoptotic state.
      We have demonstrated that Fabry disease peripheral blood mononuclear cells
      display a higher apoptotic state, which is reduced by enzyme replacement therapy
      (ERT), and is mediated, at least in part, by activation of the intrinsic pathway
      of caspases. We could rule out the implication of "unfolded protein response-ER
      stress" in this apoptotic process. To further confirm the suggestion that Gb3 is
      associated to apoptotic cell death, we treated normal cells with Gb3 at
      concentrations found in Fabry patients. Addition of Gb3 resulted in a dose
      dependent induction of apoptosis involving the intrinsic pathway. In summary,
      PBMC from Fabry patients display a higher apoptotic state, which could be mainly
      related to elevated Gb3.

PMID- 21724438
TI  - A strategic development model for the role of the biomedical physicist in the
      education of healthcare professionals in Europe.
AB  - This is the third of a series of articles targeted at biomedical physicists
      providing educational services to other healthcare professions, whether in a
      university faculty of medicine/health sciences or otherwise (e.g., faculty of
      science, hospital-based medical physics department). The first paper identified
      the past and present role of the biomedical physicist in the education of the
      healthcare professions and highlighted issues of concern. The second paper
      reported the results of a comprehensive SWOT (strengths, weaknesses,
      opportunities, threats) audit of that role. In this paper we present a strategy
      for the development of the role based on the outcomes of the SWOT audit. The
      research methods adopted focus on the importance of strategic planning at all
      levels in the provision of educational services. The analytical process used in
      the study was a pragmatic blend of the various theoretical frameworks described
      in the literature on strategic planning research as adapted for use in academic
      role development. Important results included identification of the core
      competences of the biomedical physicist in this context; specification of
      benchmarking schemes based on experiences of other biomedical disciplines;
      formulation of detailed mission and vision statements; gap analysis for the role.
      The paper concludes with a set of strategies and specific actions for gap
      reduction.

PMID- 21724437
TI  - Alterations in membrane caveolae and BKCa channel activity in skin fibroblasts in
      Smith-Lemli-Opitz syndrome.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol
      synthesis caused by mutations in DHCR7 which encodes the final enzyme in the
      cholesterol synthesis pathway. The immediate precursor to cholesterol synthesis,
      7-dehydrocholesterol (7-DHC) accumulates in the plasma and cells of SLOS patients
      which has led to the idea that the accumulation of abnormal sterols and/or
      reduction in cholesterol underlies the phenotypic abnormalities of SLOS. We
      tested the hypothesis that 7-DHC accumulates in membrane caveolae where it
      disturbs caveolar bilayer structure-function. Membrane caveolae from skin
      fibroblasts obtained from SLOS patients were isolated and found to accumulate 7
      DHC. In caveolar-like model membranes containing 7-DHC, subtle, but complex
      alterations in intermolecular packing, lipid order and membrane width were
      observed. In addition, the BK(Ca) K(+) channel, which co-migrates with caveolin-1
      in a membrane fraction enriched with cholesterol, was impaired in SLOS cells as
      reflected by reduced single channel conductance and a 50 mV rightward shift in
      the channel activation voltage. In addition, a marked decrease in BK(Ca) protein
      but not mRNA expression levels was seen suggesting post-translational
      alterations. Accompanying these changes was a reduction in caveolin-1 protein and
      mRNA levels, but membrane caveolar structure was not altered. These results are
      consistent with the hypothesis that 7-DHC accumulation in the caveolar membrane
      results in defective caveolar signaling. However, additional cellular alterations
      beyond mere changes associated with abnormal sterols in the membrane likely
      contribute to the pathogenesis of SLOS.

PMID- 21724439
TI  - [Loss of power by Primary Care nursing directives].

PMID- 21724440
TI  - [Pathogen reduction for platelets: available techniques and recent developments].
AB  - The will to reach for blood components a microbiological safety comparable to
      that of plasma-derived drugs led to the development of numerous pathogen
      reduction research programs for red blood cells and?or platelets in the 1990s. A
      consensus conference organized in 2007 allowed to define the main steps and
      precautions to be taken for the implementation of these processes. In the
      specific case of platelet concentrates, three processes stay this day in the run,
      even if they are not at the same development stage. A process using ultraviolet C
      only is at the stage of preclinical studies. The Mirasol(r) process, based on the
      activation of riboflavin by exposure to ultraviolet A and ultraviolet B is CE
      marked (class IIb), and a clinical study was published in 2010. The Intercept(r)
      process, involving the activation of a psoralen molecule by exposure to
      ultraviolet A, is CE marked (class III) since 2002, and has been licensed in
      France since 2005, in Germany since 2005 and in Switzerland since 2010. At least
      12 clinical studies have been published. In regard to this last pathogen
      reduction process, the medical and scientific documentation, from in vitro
      investigations to post-marketing observational studies, is much more developed
      than the corresponding documentation of some innovative processes at the time of
      their generalization, such as the SAG-mannitol solution for red cell concentrates
      in 1979, leukoreduction filters for platelets and red cells concentrates in the
      1990s, the solvent detergent therapeutic plasma in 1992 or the methylene blue
      therapeutic plasma in 2006.

PMID- 21724441
TI  - Unusual seminoma revealed by bone metastasis.
AB  - We report a first case of primitive mediastinal seminoma revealed by bone
      metastasis without testicular tumor. In a 24-year-old patient with a 6-month
      history of isolated right hip pain, having normal X-ray and blood tests, we
      discovered a clinically silent chest mass being diagnosed as seminoma on needle
      biopsy. Etoposide-ifosfamide-cisplatin chemotherapy was chosen because of the
      presence of multiple lesions and its lesser toxicity. Germ cell tumors are a rare
      cause of bone metastases and need to be known to rheumatologists because of their
      excellent prognosis when recognized and treated early. We discuss new diagnostic
      (CT, MRI and PET-Scan) and treatment (chemotherapy and radiotherapy) strategies
      applied to our patient.

PMID- 21724442
TI  - Suggestive linkage to chromosome 1q for bone mineral apparent density in
      Brazilian sister adolescents.
AB  - OBJECTIVE: To investigate linkage to chromosome 1q and 11q region for lumbar
      spine, femoral neck and total body BMD and volumetric BMD in Brazilian sister
      adolescents aged 10-20-year-old and 57 mothers. METHODS: We evaluated 161 sister
      pairs (n=329) aged 10-20 years old and 57 of their mothers in this study.
      Physical traits and lifestyle factors were collected as covariates for lumbar
      spine (LS), femoral neck (FN) and total body (TB) BMD and bone mineral apparent
      density (BMAD). We selected nine microsatellite markers in chromosome 1q region
      (spanning nearly 33cM) and eight in chromosome 11q region (spanning nearly 34cM)
      to perform linkage analysis. RESULTS: The highest LOD score values obtained from
      our data were in sister pairs LS BMAD analysis. Their values were: 1.32
      (P<0.006), 2.61 (P<0.0002) and 2.44 (P<0.0004) in D1S218, D1S2640 and D1S2623
      markers, respectively. No significant LOD score was found with LS and FN BMD/BMAD
      in chromosome 11q region. Only TB BMD showed significant linkage higher than 1.0
      for chromosome 11q region in the markers D11S4191 and D11S937.
      DISCUSSION/CONCLUSIONS: Our results provided suggestive linkage for LS BMAD at
      D1S2640 marker in adolescent sister pairs and suggest a possible candidate gene
      (LHX4) related to adolescent LS BMAD in this region. These results reinforce
      chromosome 1q21-23 as a candidate region to harbor one or more bone
      formation/maintenance gene. In the other hand, it did not repeat for chromosome
      11q12-13 in our population.

PMID- 21724443
TI  - Treatment adherence in patients with gout.
AB  - The treatment objectives in gout are to promptly terminate the acute flares and
      to prevent the long-term complications via chronic pharmacotherapy, usually with
      urate-lowering drugs, combined with diet and lifestyle changes. Published data
      indicate that adherence with pharmacotherapy is particularly poor in gout
      patients. In studies of pharmacy dispensing of gout medications, the percentage
      of patients with good adherence, defined as purchasing at least 80% of the
      prescribed amount of medication, ranged from 18 to 44%. In a comparative study
      showing a 36.8% adherence rate among gout patients, patients with hypertension or
      type 2 diabetes had considerably higher rates, of 72.3 and 65.4%, respectively.
      In addition, data are lacking on adherence to recommended dietary and lifestyle
      changes, whose importance has been emphasized in recent years. Poor adherence has
      well-documented adverse consequences on the treatment success rate and on disease
      progression. These data identify treatment adherence in gout as a key target of
      patient education.

PMID- 21724444
TI  - Efficacy of rituximab in the treatment of rheumatoid arthritis. Influence of
      serologic status, coprescription of methotrexate and prior TNF-alpha inhibitors
      exposure.
AB  - PURPOSE: Rituximab has been shown to be efficient in the treatment of rheumatoid
      arthritis (RA) when associated with methotrexate (MTX). The purpose of this study
      was to evaluate the response to this treatment in daily practice in the following
      three specific situations: rheumatoid factor (RF)-negative RA patients, rituximab
      monotherapy patients and TNFalpha inhibitors-naive patients. METHODS: This
      retrospective observational study is an exploratory analysis of the response to
      rituximab. One thousand milligrams (1000 mg) of rituximab was administered twice
      at an interval of 15 days. Therapeutic response was determined at mean 20 weeks
      after the infusion on the basis of DAS28 scores and EULAR response criteria.
      RESULTS: One hundred and eight patients were included in the study and the
      responses of 95 of these were evaluated. Of the latter, 75% were EULAR
      responders. There was no significant difference in EULAR response between
      patients treated with rituximab and MTX (73.8%) and those who had received
      rituximab alone (79.3%). Similarly, there was no difference in the number of
      EULAR responders between patients who had received TNF inhibitor beforehand
      (74.1%) and those who had not (78.6%). However, interval to retreatment was
      significantly shorter in TNF inhibitor-naive patients. Lastly, a significant
      difference (P=0.02) in EULAR response rate was observed between RF-positive
      patients (84.8%) and RF-negative patients (57.9%). Interval to retreatment was
      also significantly shorter in RF-negative patients. CONCLUSION: In our
      experience, while our RTX efficacy findings appear to be consistent with the
      results of comparable controlled trials, whether or not in association with MTX,
      or with prior administration of one or several TNF inhibitors, RF-positive RA
      patients exhibited a higher EULAR response rate than RF-negative RA patients.

PMID- 21724445
TI  - Bone turnover markers for osteoporotic status assessment? A systematic review of
      their diagnosis value at baseline in osteoporosis.
AB  - OBJECTIVE: Osteoporosis diagnosis is based on bone mineral density (BMD) but bone
      remodeling is also a crucial issue. It can be assessed by bone turnover markers
      (BTMs). Their interest for the positive and etiological diagnosis of osteoporosis
      at baseline, and their predictive value for past asymptomatic vertebral
      fractures, were evaluated by a systematic review of the literature. METHODS:
      Medline database was searched to identify all published reports analyzing BTMs
      and BMD or fractures. We conducted meta-analyses on BTMs levels according to
      osteoporotic status using random effects models. RESULTS: Moderate and negative
      correlations were found, mainly in postmenopausal women, between BTMs and BMD,
      especially with bone alkaline phosphatase (bone ALP), osteocalcin, serum C
      terminal and urine N-terminal crosslinking telopeptides of type I collagen (sCTX
      and uNTX). Bone ALP and sCTX levels are higher in osteoporotic patients compared
      to controls. High levels of bone ALP in primary hyperparathyroidism and low
      levels of osteocalcin in endogenous hypercorticism are the most relevant data
      reported in endocrine diseases associated with osteoporosis. High levels of BTMs,
      especially osteocalcin, bone ALP or sCTX, may be associated with prevalent
      vertebral fractures. CONCLUSION: The diagnosis value of BTMs at baseline in
      osteoporosis is very low. The interest of BTMs for the etiological diagnostic of
      secondary osteoporosis has not been demonstrated. Data are lacking to address the
      interest of BTMs assessment to screen for vertebral fractures in asymptomatic
      patients with high risk factors of fractures.

PMID- 21724446
TI  - Effects of parkinsonism on health status in welding exposed workers.
AB  - BACKGROUND: Previous studies suggest that welders frequently display parkinsonian
      signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian
      findings are associated with reductions in quality of life (QoL) or health status
      could have important repercussions for worker safety and performance. METHODS:
      Subjects included 394 active workers exposed to welding fumes and evaluated for
      parkinsonism by movement disorders experts in a worksite-based epidemiology
      study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease
      Rating Scale motor subsection part 3 (UPDRS3) score was >=15. All subjects
      completed a Parkinson's disease (PD) symptom questionnaire and the PDQ39, a
      widely used QoL and health status measure for PD. RESULTS: Total PDQ39 score and
      all subscores were greater in welders with parkinsonism than welders without
      parkinsonism, with the most significant differences observed for mobility,
      emotional well-being, and activities of daily living (ADL's). The PDQ39 scores
      for welding exposed workers with parkinsonism were similar to scores seen in a
      group of early PD patients. CONCLUSION: Parkinsonism in active, welding exposed
      workers is associated with reductions in health status and QoL affecting a broad
      range of categories and within the range seen in early PD.

PMID- 21724447
TI  - Efficiency of hit generation and structural characterization in fragment-based
      ligand discovery.
AB  - Fragment-based ligand discovery constitutes a useful strategy for the generation
      of high affinity ligands with suitable physico-chemical properties to serve as
      drug leads. There is an increasing number of generic biophysical screening
      strategies established with the potential for accelerating the generation of
      useful fragment hits. Crystal structures of these hits can subsequently be used
      as starting points for fragment evolution to high affinity ligands. Emerging
      understanding of the efficiency and operative aspects of hit generation and
      structural characterization in FBLD suggests that this method should be well
      suited for academic ligand development of chemical tools and experimental
      therapeutics.

PMID- 21724448
TI  - Impact of image-guided radiotherapy to reduce laryngeal edema following treatment
      for non-laryngeal and non-hypopharyngeal head and neck cancers.
AB  - We would like to determine the effectiveness of image-guided radiotherapy (IGRT)
      to reduce laryngeal edema following treatment for head and neck cancer and to
      assess patient perception of voice and speech after treatment. We conducted a
      retrospective review of 44 patients undergoing radiation for non-laryngeal and
      non-hypopharyngeal head and neck cancers. Endoscopic and/or mirror examinations
      of the larynx were performed following radiotherapy at each follow-up visit.
      Laryngeal edema was assessed based on the Radiation Therapy Oncology Group
      grading scale. Patients were also asked to rate about the voice and speech
      quality relative to their pre-radiotherapy status. The mean laryngeal dose was
      16.3 Gy (range: 11.7-45.5 Gy). At a median follow-up of 14 months (range: 2-31
      months), three patients (7%) developed laryngeal edema (one grade 1, two grade
      2). The mean laryngeal dose was respectively 20.3 Gy in two patients and 20.7 Gy
      in the third patient developing laryngeal edema. Except for one patient who
      continued to smoke and drink after radiotherapy, no patient reported any
      significant change in voice and speech quality after treatment. IGRT results in
      low rates and low severity of laryngeal edema following treatment for non
      laryngeal and non-hypopharyngeal head and neck cancers and may preserve voice
      quality.

PMID- 21724449
TI  - Thalidomide induces apoptosis in human oral squamous cell carcinoma cell line
      with altered expression of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL).

PMID- 21724450
TI  - Iron homeostasis--Achilles' heel of Aspergillus fumigatus?
AB  - The opportunistic fungal pathogen Aspergillus fumigatus adapts to iron limitation
      by upregulation of iron uptake mechanisms including siderophore biosynthesis and
      downregulation of iron-consuming pathways to spare iron. These metabolic changes
      depend mainly on the transcription factor HapX. Consistent with the crucial role
      of iron in pathophysiology, genetic inactivation of either HapX or the
      siderophore system attenuates virulence of A. fumigatus in a murine model of
      aspergillosis. The differences in iron handling between mammals and fungi might
      serve to improve therapy and diagnosis of fungal infections.

PMID- 21724451
TI  - A study of the interaction between rhodamine 6g and hydroxy propyl beta
      cyclodextrin by steady state fluorescence.
AB  - The binding of rhodamine 6G and hydroxy propyl beta-cyclodextrin (Hbeta-CD) was
      investigated measuring fluorescence and absorption at pH 7.0. The solid inclusion
      complex of Rh6G and Hbeta-CD has been studied by Ultraviolet (UV) spectroscopy,
      Fluorimetry, Fourier Transform Infrared (FTIR), (1)H Nuclear Magnetic Resonance
      ((1)HNMR) and in the Scanning Electron Microscope (SEM). Association constant
      K(g) and K(e) were determined by the enhancement of the fluorescence of rhodamine
      6G in the presence of Hbeta-CD. Fluorescence of Rh6G is generally enhanced, in
      complexes of Rh6G and beta-Cyclodextrin in aqueous solutions. The free energy
      change for the ground state (DeltaG(g)) and for the excited state (DeltaG(e))
      have also been determined. The experimental results indicated that the inclusion
      process is an exothermic and spontaneous.

PMID- 21724452
TI  - Spectroscopic and structural properties of N-(acetamide) morpholinium bromide.
AB  - A new crystal of N-(acetamide) morpholinium (NAM) bromide has been prepared in
      methanol at room temperature and characterized by single crystal X-ray analysis,
      elemental analysis, GS-MS, FTIR, NMR((1)H,(13)C, DEPTH and HETCOR). The N
      (acetamide) morpholinium crystallizes in the orthorhombic crystal system, Pnma
      with unit cell a=12.798(9) A, b=7.222(5) A, c=9.244(5) A, beta=90.00, V=854.4(9)
      A(3), Z=4. The X-ray structure determination revealed that there are strong inner
      and intermolecular hydrogen bonds in the crystal.

PMID- 21724453
TI  - Photophysics of representative ketocyanine dyes: dependence on molecular
      structure.
AB  - Spectral properties of a new fluorescent ketocyanine dye have been discussed. The
      energy of maximum absorption/fluorescence of the dye exhibits bathochromic shift
      with increasing polarity of the medium. Both dipolarity-polarisability and
      hydrogen bond donation interaction contribute to solvation of the dye. Study of
      fluorescence parameters points to existence of different emitting states of the
      dye for aprotic and protic solvents. While the emitting state is the (1)(pi, pi*)
      state for aprotic solvents, fluorescence supposedly take place from a different
      emitting state involving H-bond formation in the excited state in protic
      solvents. Fluorescence parameters of the dye have been compared with those for a
      structurally similar symmetric ketocyanine dye. The faster decay of the dye
      relative to its symmetric counterpart has been explained as due to an increase of
      nonradiative decay.

PMID- 21724454
TI  - Density functional theory calculations of structure, FT-IR and Raman spectra of S
      phenyl thioacetate.
AB  - The infrared (4000-400 cm(-1)) and Raman spectra (3700-100 cm(-1)) of liquid S
      phenyl thioacetate have been recorded. Molecular geometry, vibrational
      frequencies and the corresponding assignments were performed by density funtional
      theory (DFT) using the 6-311++G(d,p) basis set. Two conformers have been
      identified. One is syn form where the carbonyl group is on the same side of the
      phenyl ring and the other is the anti form. The energy difference between these
      two configurations is about 1.63 kcal mol(-1) at B3LYP/6-311++G(d,p) level. By
      utilizing the more stable syn conformer, a complete assignment of the observed
      frequencies is given according to the total energy distribution of the
      vibrational modes. The general agreements between the observed and the calculated
      frequencies are shown.

PMID- 21724455
TI  - Probing the compound (E)-5-(diethylamino)-2-[(4-methylphenylimino)methyl]phenol
      mainly from the point of tautomerism in solvent media and the solid state by
      experimental and computational methods.
AB  - In this study, the molecular structure and spectroscopic properties of (E)-5
      (diethylamino)-2-[(4-methylphenylimino)methyl]phenol were characterized
      experimentally by X-ray diffraction, FT-IR and UV-vis spectroscopic techniques
      and computationally by DFT method. It is concluded on the basis of X-ray
      diffraction and FT-IR analyses that the title compound exists in enol form in the
      solid state. UV-vis spectra of the title compound were recorded in different
      organic solvents to investigate the dependence of tautomerism on solvent types.
      The tautomerism-solvent relation was also studied by computational methods to
      have more insight on structural properties. The geometry optimization of the
      title compound in gas phase was performed by using DFT (B3LYP) method with 6
      311G(d,p) basis set. The geometry optimizations in solvent media were carried out
      at the same theory level by the polarizable continuum model (PCM). In the
      calculation of excitation energies, TD-DFT calculations were carried out in both
      gas and solution phases. The computational investigation of non-linear optical
      properties indicates that the title compound has a good second order nonlinear
      optical property. The thermodynamic properties were obtained in the range of 100
      500 K.

PMID- 21724456
TI  - Social care informatics as an essential part of holistic health care: a call for
      action.
AB  - PURPOSE: The authors identified the need for a cross-disciplinary research view
      of issues to ensure an integrated citizen-centric support to achieve optimal
      health of individual citizens and, in particular, the role of informatics to
      inform and coordinate support towards integrated and holistic care. METHOD: An
      Exploratory Workshop was approved and sponsored by the European Science
      Foundation. Twenty-three participants from 15 countries attended, covering a full
      range of health, social care and informatics professions and disciplines.
      RESULTS: The participants found strong common ground in identifying key issues to
      be addressed if citizens with compromised health are to receive integrated and
      coordinated support to a common set of objectives, while also ensuring
      appropriate choice and support for citizen, family and other informal carers. At
      the same time, optimal health was identified as a fundamental human right, and
      that achieving this is a necessary priority of a caring society. Moreover, Europe
      has a commitment to researching and developing health informatics (e-health),
      though not yet giving a priority to this integration of health and social care.
      Specifically the following main informatics challenges to be addressed were
      identified: (1) to identify available information and communication needs related
      to different scenarios of use in the intersection between health and social care,
      (2) to develop and map shared ontologies, and standards for integration and/or
      brokerage, (3) to enable planned information access and sharing, shaping a system
      of trust where the patient is an active partner and policies are established
      considering all partners/interests, (4) to investigate the use of
      automatic/intelligent knowledge based and context-relevant services, and (5)
      empowering the citizen (or their selected agent) as co-producer through modern
      informatics tools, while carefully avoiding selective disempowerment of the most
      vulnerable. CONCLUSION: The Exploratory Workshop resulted in a unanimous
      Declaration for action, which is presented appended to this paper.

PMID- 21724457
TI  - Rate of detection of high-risk HPV with two assays in women >= 30 years of age.
AB  - BACKGROUND: High-risk (HR) human papillomavirus (HPV) prevalence rates, as
      determined by the Cervista((r)) HPV HR test, in women aged >=30 years in a
      routine screening population have not been studied. OBJECTIVES: The primary
      objective of this study was to estimate HR HPV prevalence in women negative for
      intraepithelial lesion or malignancy (NILM) cytology using the CERVISTA HPV HR
      test. The study also compared HR HPV prevalence rates in women aged >=30 years
      and NILM cytology using the CERVISTA HPV HR and Hybrid Capture((r)) 2 (hc2)
      tests. STUDY DESIGN: A multi-center study was conducted to analyze HR HPV
      prevalence rates using the CERVISTA HPV HR test from residual ThinPrep((r))
      specimens. HR HPV positive rates were determined for hc2; percent agreement
      between the CERVISTA HPV HR and the hc2 tests were reported. RESULTS: HR HPV
      prevalence rates among women with NILM cytology were not statistically different
      between the CERVISTA HPV HR and hc2 tests (6.92% [98/1417] versus 5.93%
      [84/1417], respectively; P>0.05). The overall percent agreement between the tests
      was 95.3% (1351/1417; 95% confidence interval [CI]: 94.1-96.3; kappa=0.61, 95%
      CI: 0.53-0.70). There were no statistically significant differences between tests
      across age groups or investigational sites. For both tests, there was a
      statistically significant decrease in HR HPV positive results as age increases
      (CERVISTA HPV HR, P=0.0009; hc2, P<0.0001). DISCUSSION: There is no statistically
      significant difference between HR HPV prevalence rates obtained with the CERVISTA
      HPV HR and hc2 tests in women aged >=30 years with NILM cytology.

PMID- 21724458
TI  - Exploring the physiology and function of high-frequency oscillations (HFOs) from
      the somatosensory cortex.
AB  - A brief review of previous studies is presented on high frequency oscillations
      (HFOs)>300 Hz overlying the cortical response in the somatosensory evoked
      potential (SEP) or magnetic field (SEF) in humans as well as other mammals. The
      characteristics of somatosensory HFOs are described about reproducibility and
      origin (area 3b and 1) of the HFOs, changes during a wake-sleep cycle, effects of
      stimulus rate or tactile interference, and pharmacological effects. Also, several
      hypotheses on the neural mechanisms of the HFOs are reconsidered; the early HFO
      burst is probably generated from action potentials of thalamocortical fibers at
      the time when they arrive at the area 3b (and 1), since this component is
      resistant to higher stimulus rate >10 Hz, general anesthesia, or application of
      glutamatergic receptor antagonist: by contrast, the late HFO burst is sensitive
      to higher stimulus rate and eliminated after application of glutamatergic
      receptor antagonist, reflecting activities of a postsynaptic neural network in
      areas 3b and 1 of the somatosensory cortex. In view of physiological features of
      the somatosensory HFOs and their pathological or pharmacological changes,
      possible mechanisms of the late HFO burst genesis are discussed: a fast-spiking
      interneuron hypothesis, a fast pyramidal cell IPSP hypothesis and a chattering
      cell hypothesis.

PMID- 21724459
TI  - Influence of blood viscosity to cerebral blood flow in older humans compared to
      young subjects.
AB  - OBJECTIVE: Since blood viscosity (BV) is one of the most important factors
      determining blood flow, this study aimed to investigate the possible correlation
      between increased blood viscosity and reduction of regional cerebral blood flow
      (rCBF) in healthy ageing. METHODS: Male subjects were distributed in two groups:
      "young", aged 20-30 (27 volunteers), or "elderly", aged 60-70 (50 volunteers).
      Whole blood viscosity was obtained with a Wells-Brookfield Cone/Plate Viscometer.
      Cerebral blood flow was analysed by means of single photon emission computed
      tomography (SPECT). RESULTS: The mean BV values were 3.28+/-0.43 mPa in the group
      of young volunteers and 4.33+/-0.73 mPa in the group of elderly volunteers (t=
      6.9, p<0.0001). The elderly had a lower blood flow than the young in the
      following regions: bilateral parietal; temporal-parietal and temporal of the left
      hemisphere. Pearson's correlation between BV and rCBF showed a good inverse
      correlation when the BV was above 3.95+/-0.83 mPa. CONCLUSIONS: Our results point
      to a close relationship between the two parameters analysed, BV and rCBF. The
      impairment in rCBF observed in the elderly volunteers might be due to an increase
      in BV, among other factors. SIGNIFICANCE: These findings suggest interesting
      possibilities for the treatment/prevention of brain ageing.

PMID- 21724460
TI  - Sleep disordered breathing in community dwelling elderly: associations with
      cardiovascular disease, impaired systolic function, and mortality after a six
      year follow-up.
AB  - INTRODUCTION: Sleep disordered breathing (SDB), cardiovascular disease (CVD) and
      impaired cardiac function are common in elderly people. We investigated the
      association of SDB and mortality in a community dwelling elderly population,
      considering CVD and objectively measured impaired cardiac function have been
      poorly studied thus far. AIM: To investigate whether SDB is a factor that affects
      mortality in elderly people, with a focus on those with CVD and/or signs of
      impaired cardiac function. METHODS: A prospective cohort design was used and 331
      community dwelling elderly aged 71-87 years underwent one-night polygraphic
      recordings in the subjects' homes. CVD and systolic function were objectively
      established. Mortality data were collected after 6 years. RESULTS: In the total
      population there were no significant associations between mortality and SDB. In
      those with CVD and impaired systolic function, as measured by NT-proBNP, oxygen
      desaturation index (ODI) >=10 was associated with mortality. The hazard ratio of
      3.0 (CI 95% 1.1-8.6, p=0.03) remained statistically significant after adjustments
      for age, gender, diabetes and plasma values of NT-proBNP. CONCLUSION: SDB in
      community dwelling elderly has no overall association to mortality irrespective
      of degree of SDB. However, hypoxic events (i.e., ODI >=10) were associated with
      mortality in the group who had CVD in combination with impaired systolic
      function.

PMID- 21724461
TI  - The challenge of recurrent follicular lymphoma.

PMID- 21724463
TI  - The use of multiscale systems biology approaches to facilitate understanding of
      complex control systems for airway protection.
AB  - Airway protection is a critically important function that prevents/limits the
      intrusion of foreign material into the pulmonary tree. A host of different
      behaviors participate in this process. The control, coordination, and execution
      of these behaviors is a complex process that has recently received increased
      attention. Data from human clinical and animal studies support the concept of a
      coordinated neural control system that governs the appropriate expression and
      sequencing of airway protective behaviors. Our current knowledge of the proposed
      neural control network for breathing, cough, swallow and other airway protective
      behaviors indicates that it is a highly complex system that can 'rewire'
      (reconfigure) itself to perform several different functions. Computational
      modeling and simulation have been used as tools to investigate this system. The
      results of modeling efforts have yielded motor output patterns of upper airway
      and respiratory muscles that are very similar to those recorded in vivo.
      Regulation and coordination of multiple different airway protective behaviors
      have been successfully simulated. Outcomes of simulation efforts support the
      hypothesis that computational modeling of airway protection can yield important
      testable hypotheses regarding brainstem neural network functions and
      organization. Modeling of complex systems can be challenging but the open
      availability of straight-forward computational tools is likely to result in
      increased implementation of modeling and simulation as adjuncts to traditional
      methods of investigation of the control of the upper airway.

PMID- 21724464
TI  - Pharmacologic therapy for cough.
AB  - Cough is the commonest symptom for which patients seek medical care and yet
      effective, well-tolerated cough medicines remain a significant unmet clinical
      need. The development of anti-tussive agents has probably been restricted by a
      number of factors; our understanding of the specific mechanisms evoking cough in
      different diseases and how this differs from the role of cough as a protective
      reflex is limited. Also well-validated tools for the assessment of cough have
      been lacking. These issues have not encouraged investment by the pharmaceutical
      industry and there have been no new licensed treatments for cough in more than 50
      years. This article will use a mechanism-based approach to discuss the clinical
      evidence for the anti-tussive activity of currently available agents.

PMID- 21724465
TI  - Disease causing mutations in the TNF and TNFR superfamilies: Focus on molecular
      mechanisms driving disease.
AB  - The tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies comprise
      multidomain proteins with diverse roles in cell activation, proliferation and
      cell death. These proteins play pivotal roles in the initiation, maintenance and
      termination of immune responses and have vital roles outside the immune system.
      The discovery and analysis of diseases associated with mutations in these
      families has revealed crucial mechanistic details of their normal functions. This
      review focuses on mutations causing four different diseases, which represent
      distinct pathological mechanisms that can exist within these superfamilies:
      autoimmune lymphoproliferative syndrome (ALPS; FAS mutations), common variable
      immunodeficiency (CVID; TACI mutations), tumor necrosis factor receptor
      associated periodic syndrome (TRAPS; TNFR1 mutations) and hypohidrotic ectodermal
      dysplasia (HED; EDA1/EDAR mutations). In particular, we highlight how mutations
      have revealed information about normal receptor-ligand function and how such
      studies might direct new therapeutic approaches.

PMID- 21724466
TI  - Bile acids and colon cancer: Solving the puzzle with nuclear receptors.
AB  - Colorectal cancer is the third most common malignancy worldwide and is often
      linked to obesity, a sedentary lifestyle, carbohydrate- and fat-rich diets and
      elevated fecal excretion of secondary bile acids. Accumulation of toxic bile
      acids triggers oxidative damage, mitochondrial dysfunction and tumor progression.
      Nuclear receptors are transcription factors crucially involved in the regulation
      of bile acid metabolism and detoxification, and their activation may confer
      protection from bile acid tumor-promoting activity. In this review, we explore
      the tangled relationships among bile acids, nuclear receptors and the intestinal
      epithelium, with particular emphasis on the role of the farnesoid X receptor in
      colorectal cancer prevention and on novel nuclear receptor-based approaches to
      expand the portfolio of chemotherapeutic agents.

PMID- 21724462
TI  - Bortezomib plus rituximab versus rituximab alone in patients with relapsed,
      rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3
      trial.
AB  - BACKGROUND: Bortezomib and rituximab have shown additive activity in preclinical
      models of lymphoma, and have been shown to be active and generally well tolerated
      in a randomised phase 2 study in patients with follicular and marginal zone
      lymphoma. We compared the efficacy and safety of rituximab alone or combined with
      bortezomib in patients with relapsed or refractory follicular lymphoma in a phase
      3 setting. METHODS: In this multicentre phase 3 trial, rituximab-naive or
      rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2
      follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles
      consisting of intravenous infusions of rituximab 375 mg/m(2) on days 1, 8, 15,
      and 22 of cycle 1, and on day 1 of cycles 2-5, either alone or with bortezomib
      1.6 mg/m(2), administered by intravenous injection on days 1, 8, 15, and 22 of
      all cycles. Randomisation was stratified by FLIPI score, previous use of
      rituximab, time since last therapy, and region. Treatment assignment was based on
      a computer-generated randomisation schedule prepared by the sponsor. Patients and
      treating physicians were not masked to treatment allocation. The primary endpoint
      was progression-free survival analysed by intention to treat. This trial has been
      completed and is registered with ClinicalTrials.gov, number NCT00312845.
      FINDINGS: Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised
      to receive rituximab (n=340) or bortezomib plus rituximab (n=336). After a median
      follow-up of 33.9 months (IQR 26.4-39.7), median progression-free survival was
      11.0 months (95% CI 9.1-12.0) in the rituximab group and 12.8 months (11.5-15.0)
      in the bortezomib plus rituximab group (hazard ratio 0.82, 95% CI 0.68-0.99;
      p=0.039). The magnitude of clinical benefit was not as large as the anticipated
      prespecified improvement of 33% in progression-free survival. Patients in both
      groups received a median of five treatment cycles (range 1-5); 245 of 339 (72%)
      and 237 of 334 (71%) patients in the rituximab and bortezomib plus rituximab
      groups, respectively, completed five cycles. Of patients who did not complete
      five cycles, most discontinued early because of disease progression (77 [23%]
      patients in the rituximab group, and 56 [17%] patients in the bortezomib plus
      rituximab group). Rates of adverse events of grade 3 or higher (70 [21%] of 339
      rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated
      patients), and serious adverse events (37 [11%] patients vs 59 [18%] patients)
      were lower in the rituximab group than in the combination group. The most common
      adverse events of grade 3 or higher were neutropenia (15 [4%] patients in the
      rituximab group and 37 [11%] patients in the bortezomib plus rituximab group),
      infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhoea (no
      patients and 25 [7%] patients, respectively), herpes zoster (one [<1%] patient
      and 12 [4%] patients, respectively), nausea or vomiting (two [<1%] patients and
      10 [3%] patients, respectively) and thrombocytopenia (two [<1%] patients and 10
      [3%] patients, respectively). No individual serious adverse event was reported by
      more than three patients in the rituximab group; in the bortezomib plus rituximab
      group, only pneumonia (seven patients [2%]) and pyrexia (six patients [2%]) were
      reported in more than five patients. In the bortezomib plus rituximab group 57
      (17%) of 334 patients had peripheral neuropathy (including sensory, motor, and
      sensorimotor neuropathy), including nine (3%) with grade 3 or higher, compared
      with three (1%) of 339 patients in the rituximab group (no events of grade >=3).
      No patients in the rituximab group but three (1%) patients in the bortezomib plus
      rituximab group died of adverse events considered at least possibly related to
      treatment. INTERPRETATION: Although a regimen of bortezomib plus rituximab is
      feasible, the improvement in progression-free survival provided by this regimen
      versus rituximab alone was not as great as expected. The regimen might represent
      a useful addition to the armamentarium, particularly for some subgroups of
      patients. FUNDING: Johnson & Johnson Pharmaceutical Research & Development and
      Millennium Pharmaceuticals, Inc.

PMID- 21724468
TI  - The European Journal of Cardiovascular Nursing: it takes a team to make a
      journal.

PMID- 21724467
TI  - Myotonic dystrophy mouse models: towards rational therapy development.
AB  - DNA repeat expansions can result in the production of toxic RNA. RNA toxicity has
      been best characterised in the context of myotonic dystrophy. Nearly 20 mouse
      models have contributed significant and complementary insights into specific
      aspects of this novel disease mechanism. These models provide a unique resource
      to test pharmacological, anti-sense, and gene-therapy therapeutic strategies that
      target specific events of the pathobiological cascade. Further proof-of-principle
      concept studies and preclinical experiments require critical and thorough
      analysis of the multiple myotonic dystrophy transgenic lines available. This
      review provides in-depth assessment of the molecular and phenotypic features of
      these models and their contribution towards the dissection of disease mechanisms,
      and compares them with the human condition. More importantly, it provides
      critical assessment of their suitability and limitations for preclinical testing
      of emerging therapeutic strategies.

PMID- 21724469
TI  - Beliefs about the role of parenting in feeding and childhood obesity among
      mothers of lower socioeconomic status.
AB  - OBJECTIVE: To examine beliefs about the role of parenting in feeding and
      childhood obesity among mothers of lower socioeconomic status. METHODS:
      Individual semistructured, audiotaped interview with 91 mothers of preschool-aged
      children (49% of mothers obese, 21% of children obese) in the midwestern United
      States. Participant comments were transcribed and common themes were identified
      using the constant comparative method and NVivo software. RESULTS: Mothers often
      described their parents' feeding style as authoritarian or neglectful, and their
      own current style as comparatively indulgent and better. Mothers described
      parents of overweight children as inept or neglectful, but they never described
      their own parenting as such. CONCLUSIONS AND IMPLICATIONS: Encouraging mothers to
      reflect on how they were fed as children, how it may influence their current
      parenting, and how the relationship between mothering and child obesity is
      complex are important nutrition education opportunities.

PMID- 21724470
TI  - Children's perceptions of the Northern Fruit and Vegetable Program in Ontario,
      Canada.
AB  - OBJECTIVE: This study examined students' perceptions of and suggestions for the
      Northern Fruit and Vegetable Program, a free, school-based fruit and vegetable
      snack program implemented in elementary schools in 2 regions of northern Ontario,
      Canada. METHODS: This was a qualitative study involving 18 focus groups with
      students in 11 elementary schools in the Porcupine region and 7 schools in the
      Algoma region. One hundred thirty-nine students from grades 5-8 participated in
      this study. Inductive content analysis was used to identify key themes. RESULTS:
      Children perceived the Northern Fruit and Vegetable Program to be a valuable
      program that allowed them to try new fruits and vegetables (FVs). Participants
      stated they now eat more FVs at home and at school. Participants would like the
      program offered more frequently and with more variety. CONCLUSIONS AND
      IMPLICATIONS: Although children identified several areas for program improvement,
      they generally perceived the program to be positive and valuable in promoting FV
      consumption.

PMID- 21724471
TI  - Premenstrual dysphoric disorder in women with epilepsy: relationships to
      potential epileptic, antiepileptic drug, and reproductive endocrine factors.
AB  - The purpose of this prospective observational investigation was to determine
      whether the frequency of premenstrual dysphoric disorder (PMDD) and the severity
      of PMDD symptoms differ between women with epilepsy and controls without epilepsy
      and whether there exists a relationship between the severity of PMDD symptoms and
      some epileptic, antiepileptic drug, and reproductive endocrine features. The
      results suggest that epilepsy, antiepileptic drug levels, ovulatory status, and
      hormone levels and ratios may all influence PMDD in women with epilepsy. PMDD
      severity scores may be greater in people with right-sided than in those with left
      sided epilepsy, and in people with temporal than in those with nontemporal
      epileptic foci. PMDD severity scores may be greater with anovulatory cycles, and
      scores may correlate negatively with midluteal serum progesterone levels and
      positively with midluteal estradiol/progesterone ratios. Mood score may vary with
      particular antiepileptic drugs, favoring carbamazepine and lamotrigine over
      levetiracetam. PMDD severity scores may correlate directly with carbamazepine
      levels, whereas they correlate inversely with lamotrigine levels.

PMID- 21724472
TI  - Ossified lumbar pseudomeningocele: imaging findings.

PMID- 21724473
TI  - Estrogen up-regulation of semaphorin 3F correlates with sympathetic denervation
      of the rat uterus.
AB  - Current evidence indicates that rises in systemic levels of estrogen create in
      the uterus an inhibitory environment for sympathetic nerves. However, molecular
      insights of these changes are far from complete. We evaluated if semaphorin 3F
      mRNA, a sympathetic nerve repellent, was produced by the rat uterus and if its
      expression was modulated by estrogen. We also analyzed whether uterine nerves
      express the semaphorin 3F binding receptor, neuropilin-2. Uterine levels of
      semaphorin 3F mRNA were measured using real time reverse transcriptase-polymerase
      chain reaction in prepubertal rat controls and following chronic estrogen
      treatment. Localization of semaphorin 3F transcripts was determined by in situ
      hybridization and the expression of neuropilin-2 was assessed by
      immunohistochemistry. These studies showed that: (1) chronic estrogen treatment
      led to a 5-fold induction of semaphorin 3F mRNA in the immature uterus; (2)
      estrogen provoked a tissue-specific induction of semaphorin 3F which was
      particularly localized in the connective tissue that borders muscle bundles and
      surrounds intrauterine blood vessels; (3) two major cell-types were recognized in
      the areas where transcripts were concentrated, fibroblast-like cells and
      infiltrating eosinophil leukocytes; and (4) some delicate nerve terminal profiles
      present in the estrogenized uterus were immunoreactive for neuropilin-2. Temporal
      and spatial expression patterns of semaphorin 3F/neuropilin-2 are consistent with
      a possible role of this guidance cue in the remodeling of uterine sympathetic
      innervation by estrogen. Though correlative in its nature, these data support a
      model whereby semaphorin 3F, in combination with other inhibitory molecules,
      converts the estrogenized myometrium to an inhospitable environment for
      sympathetic nerves.

PMID- 21724474
TI  - Efficacy of transgene expression in porcine skin as a function of electrode
      choice.
AB  - Gene electrotransfer is a non-viral technique using electroporation for gene
      transfection. The method is widely used in the preclinical setting and results
      from the first clinical study in tumours have been published. However, the
      preclinical studies, which form the basis for the clinical trials, have mainly
      been performed in rodents and the body of evidence on electrode choice and
      optimal pulsing conditions is limited. We therefore tested plate and needle
      electrodes in vivo in porcine skin, which resembles human skin in structure. The
      luciferase (pCMV-Luc) gene was injected intradermally and subsequently
      electroporated. Simultaneously, studies with gene electrotransfer to porcine skin
      using plasmids coding for green fluorescent protein (GFP) and betagalactosidase
      were performed. Interestingly, we found needle electrodes to be more efficient
      than plate electrodes (p<0.001) and electric field calculations showed that
      penetration of the stratum corneum led to much more homogenous field distribution
      at the DNA injection site. Furthermore, we have optimised the electric pulse
      regimens for both plate and needle electrodes using a range of high voltage and
      low voltage pulse combinations. In conclusion, our data support that needle
      electrodes should be used in human clinical studies of gene electrotransfer to
      skin for improved expression.

PMID- 21724475
TI  - Determination of cysteinyl leukotrienes in exhaled breath condensate: method
      combining immunoseparation with LC-ESI-MS/MS.
AB  - A rapid and precise method for the identification and quantification of cysteinyl
      leukotrienes (leukotriene C(4), leukotriene D(4) and leukotriene E(4)), essential
      markers of bronchial asthma, in exhaled breath condensate was developed. The
      protocol consists of immunoaffinity separation and a detection step, liquid
      chromatography combined with electrospray ionization tandem mass spectrometry (LC
      ESI-MS/MS). In particular, the selected reaction monitoring mode was used for its
      extremely high degree of selectivity and the stable-isotope-dilution assay for
      its high precision of quantification. The developed method was characterized with
      a high precision (<= 7.7%, determined as RSD), an acceptable accuracy (90.4
      93.7%, determined as recovery), a low limit of detection (<= 2 pg/ml EBC) and a
      low limit of quantification (<= 10 pg/ml EBC). It was compared to other simple,
      clinically appropriate combinations of pre-treatment methods (solid phase
      extraction and lyophilization) with LC/MS. Finally, the method (a combination of
      immunoaffinity separation with LC-MS) was successfully tested in a clinical study
      where a significant difference was found in the concentration levels of cysteinyl
      leukotrienes between patients with occupational bronchial asthma and healthy
      subjects.

PMID- 21724476
TI  - A case of hemorrhagic colitis after influenza A infection.
AB  - The pandemic (H1N1) influenza virus continues to be the predominant circulating
      virus in both the northern and southern hemispheres. In February 2009, during the
      early stage of the worldwide H1N1 influenza virus (influenza A) pandemic, we
      experienced a case of hemorrhagic colitis after infection with influenza A. A 21
      year-old man with no serious disease in his past history visited our hospital
      with chief complaints of a high body temperature and pharyngeal pain. A diagnosis
      of influenza A was made using a rapid diagnosis kit (Capilia Flu A+B), and the
      patient was admitted to our hospital. After admission, the patient complained of
      a lower abdominal pain, diarrhea, and hematochezia. An emergency colonoscopy
      revealed active bleeding colitis from the sigmoid to descending colon.
      Hemorrhagic colitis was confirmed by the pathological findings of a punch biopsy
      specimen. After the administration of an antiviral drug, zanamivir hydrate (10
      mg/d), the patient's general condition and colonoscopic findings improved
      significantly. The findings of both sequential colonoscopies and intestinal
      histology strongly suggested that infection with influenza A could induce
      hemorrhagic colitis, though the incidence is quite low.

PMID- 21724477
TI  - [Renal position and fusion anomalies].
AB  - OBJECTIVES: To analyse kidney position and fusion anomalies, as well as
      associated urinary tract and extra-renal pathologies in a cohort from a tertiary
      hospital. MATERIALS AND METHODS: The medical records of 84 children with renal
      ectopia (RE) and horseshoe kidney (HK) in our hospital from 1999 to 2010 were
      retrospectively reviewed. RESULTS: Prenatal diagnosis was made in 53 patients
      (63.09%). Of the 84 patients surveyed 35 had unilateral simple renal ectopia
      (SRE), 1 had bilateral SRE; 2 had crossed renal ectopia (CRE) without fusion, 17
      had CRE with fusion, and 29 had HK. Average age was 30 days at diagnosis (IQR: 0
      12 months). In the individuals with renal ectopia (RE), the incidence of
      associated urinary tract pathologies was 20.23% in the ectopic kidney (EK) (17
      out of 84) and 17.85% in the contralateral kidney (CK) (15 out of 84). The most
      frequent urological pathology was vesico-ureteral reflux (VUR), 4 individuals had
      multicystic dysplastic kidneys (MCDK). In 4 patients renal agenesis was detected
      in the CK. In patients with HK, the incidence of associated urinary tract
      pathologies was 16.66% (14 out of 84), and the most frequent associated
      urological anomaly was also VUR. Of the 84 patients 21(25.45%) had extra-renal
      pathology. Anomalies of the skeletal system were detected in 9/84(10.71%),
      genital anomalies 5/84 (5.95%), cardiac anomalies 3/84 (3.57%), and digestive
      disease 1/84 (1.19%). Facial malformations were noted in 3/84 patients (3.57%),
      endocrine disorders 2/84 (2.38%), and 8/84 children (9.52%) suffered from
      polymalformative syndrome. During follow-up, the most frequent complication of
      the urinary tract was infection, observed in 10/84 patients (11.91%).
      CONCLUSIONS: When renal ectopia or horseshoe kidney is detected, associated renal
      and urinary anomalies and structural extra-renal malformations should be
      evaluated. Patients need long-term follow-up and should be examined regularly for
      potential complications.

PMID- 21724478
TI  - Developmental facial paralysis: a review.
AB  - The purpose of this study is to clarify the confusing nomenclature and
      pathogenesis of Developmental Facial Paralysis, and how it can be differentiated
      from other causes of facial paralysis present at birth. Differentiating
      developmental from traumatic facial paralysis noted at birth is important for
      determining prognosis, but also for medicolegal reasons. Given the dramatic
      presentation of this condition, accurate and reliable guidelines are necessary in
      order to facilitate early diagnosis and initiate appropriate therapy, while
      providing support and counselling to the family. The 30 years experience of our
      center in the management of developmental facial paralysis is dependent upon a
      thorough understanding of facial nerve embryology, anatomy, nerve physiology, and
      an appreciation of well-recognized mishaps during fetal development. It is hoped
      that a better understanding of this condition will in the future lead to early
      targeted screening, accurate diagnosis and prompt treatment in this population of
      facially disfigured patients, which will facilitate their emotional and social
      rehabilitation, and their reintegration among their peers.

PMID- 21724479
TI  - The Cake Flap: a new technique for serial excision of benign cutaneous lesions.
AB  - Large congenital melanocytic naevi and other circular benign skin lesions are
      often excised by serial ellipses in stages. With this conventional technique,
      normal skin is sacrificed when excising 'dog ears', resulting in an elongated
      scar. The 'Cake Flap' is a new technique for serial excision of benign skin
      lesions that allows more than half the area to be excised at the first operation
      without the appearance the 'dog-ears' that would occur if this was done using the
      serial excision technique commonly employed. We have used the Cake Flap in four
      patients with congenital melanocytic naevi to good effect. The design overcomes
      the shortcomings described of traditional elliptical serial excision without the
      use of tissue expansion.

PMID- 21724481
TI  - [Singular characteristics of abdominal pain in the elderly].

PMID- 21724482
TI  - [Usefulness of self-expanding biodegradable prosthesis in the treatment of
      refractory benign stenosis: a case series study].
AB  - BACKGROUND: The use of self-expanding biodegradable prosthesis treatment of
      refractory benign stenosis is still undefined. OBJECTIVE: To determine the
      utility and safety of biodegradable polydioxanone prostheses as treatment of
      gastrointestinal tract refractory benign strictures. METHODS: Consecutive
      patients diagnosed with refractory benign stricture of gastrointestinal tract
      following Kochman's criteria were included. The type of stenosis were anastomotic
      (n = 5), peptic (n = 1), post-radiotherapy (n = 1) and they were located in
      proximal esophagus-hypofarynge (n = 2), esophagus medium (n = 1), distal
      esophagus (n = 2) and rectum (n = 2). The prosthesis was placed under endoscopic
      and fluoroscopic control under conscious sedation with propofol. RESULTS: Seven
      patients (8 prosthesis) were included. Mean patient age was 49 years-old (range:
      37-70). Insertion prosthesis was successful in all cases. Distal migration of
      prosthesis was observed in both rectal stenosis and was the indication of a
      second prosthesis placement in one case. At the end of follow-up (median follow
      up 30 weeks for esophageal stricture, 33 weeks for rectal stricture) 5 patients
      remained asymptomatic. Eighty per cent of patients with esophageal stenosis
      showed partial and transient re-stenosis due to hyperplastic reaction during the
      degradation of the prosthesis, with transient dysphagia in two patients resolved
      medically. Complete prosthesis degradation was confirmed by endoscopy in all
      cases. CONCLUSIONS: The use of self-expanding biodegradable polydioxanone
      prosthesis is a safe and utile therapeutic option for refractory benign
      gastrointestinal stenosis.

PMID- 21724483
TI  - [Effect of different doses of fentanyl and butylhyoscine on the rabbit's
      sphincter of Oddi].
AB  - BACKGROUND: It was not until the advent of endoscopic retrograde
      cholangiopancreatography (ERCP) that Oddi's sphincter manometry was performed
      directly. Use of opioids for the intravenous (IV) sedation of these patients is
      controversial. OBJECTIVE: To evaluate with manometry the effect of fentanyl at
      different doses as well as the effect of butylhyoscine on the rabbit's Oddi's
      sphincter. METHODS: This is an experimental, randomized, double-blind study
      conducted in New Zealand rabbits distributed in 4 groups (control, fentanyl at
      doses of 1, 5 and 10 MUg/kg of weight) that, after laparotomy and duodenotomy,
      underwent direct Oddi's sphincter manometry. The analyzed variables included
      sphincter pressure, wave frequency, amplitude and duration. RESULTS: The baseline
      measurements of the study variables did not show any differences among the
      groups. The administration of fentanyl at 1 MUg/kg reduced Oddi's sphincter
      pressure compared with the baseline value (p = 0.003), while the doses of 5 and
      10 MUg/kg significantly increased it (p <0.0001). Butylhyoscine decreased the
      sphincter pressure, frequency, amplitude and duration of the waves in all the
      groups and antagonized the increase in pressure produced by fentanyl.
      CONCLUSIONS: Fentanyl at 1 MUg/kg of body weight relaxes the rabbit's Oddi's
      sphincter and butylhyoscine can antagonize the increased pressure of the
      sphincter caused by fentanyl at 5 and 10 MUg/kg of weight. These finding suggest
      a potential beneficial for the ERCP in clinical controlled trials in humans.

PMID- 21724484
TI  - [Metabolic bone disease in liver cirrhosis: the influence of nutritional status].
AB  - INTRODUCTION: Relationship between metabolic bone disease (MBD) and liver
      cirrhosis (LC) might be modeled by the patient's nutritional status. OBJECTIVE:
      To assess if malnourished cirrhotic patients might exhibit higher MBD rates.
      METHODS: Bone mineral density (BMD) in 50 cirrhotic patients attended at the
      Gastroenterology Service, "Hermanos Ameijeiras" Hospital, La Habana, Cuba, was
      measured at the left femur neck and lumbar column with a double-beam X-ray
      densitometer. Seventy percent of patients were male; 54% were older than 50 year
      old and 72% were white. Cause of LC was viral in 56% of patients, 62% were
      classified as Child A and 42% were considered as malnourished. MBD was
      established when "t" score <-1.0 s. LC-related MBD was compared with that
      previously observed in apparently healthy subjects. RESULTS: Mean BMD in examined
      anatomical sites was 0.957 +/- 0.149 g/cm2 in left femur neck and 0.953 +/- 0.130
      g/cm2 in lumbar spine, respectively. According to these measurements, MBD was
      diagnosed in 50% and 52% for both sites, respectively. BMD rates in cirrhotic
      patients were similar to those observed in healthy subjects after DEXA
      examination of lumbar spine. MBD was more frequent between Child C and
      malnourished cirrhotic patients. CONCLUSIONS: LC did not result in an increased
      MBD rate, however this problem presents more frequently in terminally ill and
      malnourished patients.

PMID- 21724485
TI  - [Cytokines expression in peripheral blood cells of patients with orthotopic liver
      transplant: preliminary results].
AB  - BACKGROUND: Cytokines are important in immune and inflammation response in liver
      transplantation. Determination of cytokine expression may lead to early detection
      of risk of rejection and infection in patients with this treatment. OBJECTIVE: To
      evaluate the expression of interleukin- 1beta (IL-1beta), interleukin-6 (IL-6),
      interleukin-8 (IL- 8), tumor necrosis factor-alpha (TNF-alpha), transforming
      growth factor-beta (TGF-beta) and granulocyte macrophage colony stimulating
      factor (GMCSF) in peripheral blood mononuclear cells in patients who received an
      orthotopic liver transplantation (OLT). METHODS: Fourteen patient who underwent
      OLT due to cirrhosis were analyzed before and after (at 24, 48, 72 hours, 7, 15
      and 30 days) transplantation. Peripheral blood cells were tested for IL-1beta, IL
      6, IL-8, TNF-alpha, TGF-beta and GM-CSF using semiquantitative reverse
      transcriptase-polymerase chain reaction (Roche Kit). RESULTS: No patient present
      acute rejection, and 11 of them had bacterial infections, 1 to 19 days after OTL.
      The cytokines IL-6 and TNF-alpha showed no expression in any phases studied and
      IL-1beta only in 21% in the first phase post-transplant. Sixty percent of
      patients who presented bacterial infections express GM-CSF. TGF-b was the most
      frequently expressed cytokine. CONCLUSIONS: Cytokines expression in the evaluated
      patients did not follow a defined pattern according to etiology. Increasing the
      size of the sample is deemed important to establish the implication of the
      diverse cytokines in liver transplantation.

PMID- 21724486
TI  - [Intelukin-10 expression with immunorreglatory function in the mucosa of patients
      with ulcerative colitis].
AB  - BACKGROUND: Interleukin-10 (IL-10) is an important immunoregulatory cytokine that
      acts on antigen presenting cells by the inhibiting both the synthesis of
      cytokines, co-stimulatory and HLA class II molecules. OBJECTIVE: To study the
      gene and protein expression of IL-10 in the mucosa from patients with ulcerative
      colitis (UC). METHODS: We studied 40 patients with UC and 18 controls without
      endoscopic evidence of intestinal inflammation. From rectal biopsies was
      determined the gene expression of IL- 10 by real time polymerase chain reaction
      (PCR). The detection of the protein in tissue was performed by
      immunohistochemistry. RESULTS: patients with UC in remission had significantly
      higher expression of il-10 gene in mucosa compared to the group of patients with
      active UC (p = 0.01) and the control group (p = 0.05). All patients with active
      UC had pancolitis, while patients in remission from distal inflammation, 16 had
      extra-intestinal manifestations and 23 had mild to moderate inflammation with
      less than one relapse within a year. Patients with UC in remission had
      significantly higher expression of IL-10 gene in mucosa compared with the group
      of patients with active UC (p = 0.01) or the control group (p = 0.05).
      CONCLUSIONS: The expression of IL-10 gene is increased in colonic mucosa from
      patients with UC in remission, confirming that it is an immunoregulatory cytokine
      that promotes remission in patients with UC.

PMID- 21724487
TI  - [Current management of benign and malignant bile duct strictures].
AB  - Benign and malignant bile duct strictures require multidisciplinary management.
      The radiologist, endoscopist and surgeon must assess the general conditions of
      the patient, as well as the etiology of the stenosis and the therapeutic options
      (palliative, temporal, or definitive). Stenotic injuries that maintain
      bilioenteric continuity are susceptible to radiologic and/or endoscopic
      treatment, specially benign lesions, usually appearing in the postsurgical
      period. Injuries with loss of continuity require surgical management in almost
      every case. Iatrogenic bile duct injuries with preserved continuity (Strasberg A
      and D) may be treated by endoscopy. Types B and C, in which a liver segment loses
      communication with the remaining bile tree, need surgical repair and/or
      resection. Complete sections of the bile ducts require surgical intervention,
      with hepatojejunostomy being the best choice. The use of metallic endoluminal
      stents is almost prohibited in these types of injuries. Benign, non-iatrogenic
      injuries (sclerosing cholangitis, autoimmune cholangiopathy) require surgical
      intervention in rare occasions. Malignant injuries are extremely aggressive and
      only a small percentage (less than 15%) is candidate for curative resection,
      which unfortunately does not preclude recurrence.

PMID- 21724488
TI  - [Guidelines for diagnosis and treatment of constipation in Mexico. A)
      Epidemiology (meta-analysis of the prevalence), pathophysiology and
      classification].
AB  - BACKGROUND: Constipation is a common problem in the general population and its
      prevalence is based on the diagnostic criteria, the study population and the
      research methodology for collecting the data. OBJECTIVES AND METHODS: To
      establish the clinical gudelines for diagnosis and treatment of chronic
      constipation in Mexico we have reviewed the epidemiological factors of
      constipation and have conducted meta-analysis according to the 3 available
      community-based studies from our country. In addition, evidence-based
      recommendations have been provided. RESULTS: The estimated prevalence of
      functional constipation in Mexico is 14.4% (95% CI: 12.6-16.6%) according to Rome
      II and Rome III criteria. Although constipation is present in both genders and
      all age groups, it is more common among young women with a female to male ratio
      of 3:1. In our population, 43.6% report using laxatives, teas for stimulating
      bowel movements or fiber supplements, but only 18.0% did so because they
      considered themselves as constipated. Also, data from a tertiary referral center
      in Mexico City suggests that patients with prolonged colonic transit time have
      lower scores in the physical component of the SF-36 compared to those with
      chronic constipation and a normal colonic transit time. CONCLUSIONS: Functional
      constipation is a very common problem in Mexico affecting mainly young women.
      Laxatives and other related agents are frequently used and this disorder seems to
      have a negative impact on quality of life.

PMID- 21724489
TI  - [Guidelines for diagnosis and treatment of constipation in Mexico. B) Diagnostic
      approach].
AB  - BACKGROUND: Constipation is a heterogeneous symptom so an accurate diagnosis
      requires an appropriate approach. OBJECTIVE AND METHODS: To establish the
      clinical guidelines for diagnosis and treatment of chronic constipation in Mexico
      we have reviewed the diagnostic aspects of constipation according to the
      availability of resources in our country. In addition, evidence-based
      recommendations have been provided. RESULTS: The symptoms that best define
      constipation in our population are infrequent stool, hard stool expulsion,
      excessive effort and sensation of incomplete evacuation. Digital rectal
      examination is a useful diagnostic tool to discard organic diseases and pelvic
      floor dyssynergia. Patients with risk factors such as recent onset of
      constipation, family history of inflammatory bowel disease or colon cancer and
      those with alarm signs (unintentional weight loss and significant anemia, blood
      in stool) should undergo endoscopic diagnostic studies. If they are available,
      the most useful tests in evaluating patients with functional constipation are
      colonic transit with radiopaque markers and anorectal manometry with balloon
      expulsion test. CONCLUSIONS: Patients with symptoms of chronic constipation
      should undergo advanced colorectal physiological studies to try to establish the
      cause of constipation.

PMID- 21724490
TI  - [Guidelines for diagnosis and treatment of constipation in Mexico. C) Medical and
      surgical treatment].
AB  - BACKGROUND: There are multiple therapeutic options for the management of
      constipation, from lifestyle modifications to the use of laxatives and in extreme
      cases surgery. OBJECTIVES AND METHODS: To establish the clinical guidelines for
      diagnosis and treatment of chronic constipation in Mexico we conducted a review
      of the literature regarding medical and surgical treatments for chronic
      constipation and have made recommendations based on evidence. RESULTS: Low water
      consumption, physical inactivity and low intake of fiber are conditions
      associated with chronic constipation, but the evidence to prove these
      associations is scarce. Bolus forming agents are useful in the management of
      constipation with normal colonic transit and defecation without dissynergia.
      Evidence supports the use of lactulose (IB) and polyethylene glycol (IA) as the
      most safe and effective agents in the long term in adults. The use of stimulant
      laxatives (docusate, picosulfate, senna) is recommended only for short periods.
      Tegaserod is an agonist of 5-HT4 receptors and there are many clinical trials
      supporting its effectiveness in the management of functional constipation (IA).
      However "their cardiovascular safety has been questioned recently. Biofeedback
      therapy is the gold standard in the management of constipation associated with
      pelvic floor dyssynergia. Surgical treatment is reserved for extreme cases of
      colonic inertia. CONCLUSIONS: The treatment of constipation should be based on
      the underlying pathophysiological mechanisms and the selection of drugs must be
      made according to the scientific evidence.

PMID- 21724491
TI  - [Guidelines for diagnosis and treatment of constipation in Mexico. D) Evaluation
      and treatment of constipation in pediatric population].
AB  - BACKGROUND: Constipation is one of the most common causes of consultation in
      pediatric practice, it has a multifactorial etiology and its treatment can be
      complex. OBJECTIVES AND METHODS: To establish the clinical guidelines for
      diagnosis and treatment of chronic constipation in pediatric population in
      Mexico, a review of the epidemiological, diagnostic and therapeutic aspects was
      conducted by an expert group of pediatric gastroenterologist in our country.
      RESULTS: Constipation is a symptom that reflects the presence of fecal retention,
      which is reported by patients or their relatives as decreased stool frequency,
      hard stools, and sometimes pain and excessive pushing. Constipation can occur at
      any stage of childhood. The main trigger for fecal retention is the painful
      evacuation. Patients who meet the Rome III criteria for functional constipation
      do not require diagnostic tests. The diagnostic tests are reserved for cases in
      which alarm signs are present and in patients refractory to conventional
      treatment. The goal of treatment is to promote smooth and painless evacuations
      preventing reaccumulation of stool. Osmotic laxatives such as polyethylene glycol
      and lactulose are the most effective treatments. In special cases, biofeedback
      therapy, the use of botulinum toxin and surgery can be effective, although the
      evidence is weak. CONCLUSIONS: Management of chronic constipation in pediatric
      population requires a comprehensive diagnostic approach.

PMID- 21724492
TI  - [An incidental finding of widespread cysticercosis].

PMID- 21724493
TI  - [Amelanotic anorectal melanoma].

PMID- 21724494
TI  - [Perineal endometriosis with anal external sphincter involvement: a case-report].
AB  - The presence of perianal endometriosis involving the anal sphincter is a rare
      presentation of this disease, most cases are diagnosed late and few are reported
      in the literature despite the number of episiotomies performed today. We present
      a case in a female with perianal symptoms after an episiotomy 15 years ago and
      visualized by endoanal ultrasound. We also review the literature of this
      condition. The treatment of choice is wide excision of the lesion involving the
      anal sphincter so the sphincter defect should be repaired by sphincteroplasty.
      According to the literature, early diagnosis by clinical suspicion and
      confirmation by endoanal ultrasound, with wide excision of endometrioma gives
      satisfactory results regarding anal continence.

PMID- 21724495
TI  - [Surgical treatment of a perianal giant condyloma acuminata in a HIV patient].
AB  - Buschke-Lowenstein tumor is a slowly growing neoplasm with high potential of
      local invasion. We described a 29 year-old female with acquired immunodeficiency
      syndrome who was surgically treated for a Buschke- Lowenstein tumor with a wide
      local excision, bilateral gluteal flaps and loop ileostomy. At 12 months follow
      up, there was no evidence of recurrence. Despite it does not metastasize, Buschke
      Lowenstein tumor has a high recurrence rate and a 50% risk of malignant
      transformation into squamous cell carcinoma. Surgery is considered the treatment
      of choice for this disease. Podophyllin, immunotherapy, interferon and
      radiotherapy are other treatments with a limited therapeutic response.

PMID- 21724496
TI  - [Inflammatory myoglandular polyp (Nakamura polyp): a case report].
AB  - Inflammatory myoglandular polyp (IMGP) is a rare nonneoplastic polyp of the large
      bowel, characterized by inflammatory granulation tissue in the lamina propia,
      proliferation of smooth muscle and hyperplastic glands with variable degree of
      cystic changes. Clinical course is benign and etiology unclear, but it has been
      associated to chronic inflammation due to fecal stasis and abnormal colonic
      motility. Clinically may be asymptomatic or produce hematochezia. At endoscopy
      the appearance may be that of a pedunculated or semi-pedunculated polyp, with
      soft or lobulated surface, with hyperemia and even partial erosions. We present a
      33 year-old male with hematochezia caused by an IMGP in the descending colon.
      Initial diagnosis was a well differentiated adenocarcinoma, which proved to be an
      IMGP on final pathology. Hematochezia resolved after resection.

PMID- 21724497
TI  - [Mesenteric solitary fibrous tumor: a case report and literature review].
AB  - Solitary fibrous tumors are a very unusual group of spindle-cell neoplasm of
      adults; they were described for first time in the 18th century. They locate
      mainly in parietal and visceral pleura, lung parenchyma and pericardium. There
      are numerous reports that document their extrapleural location and we can find it
      in any place in the body, but mesenteric localization is extremely unusual.

PMID- 21724498
TI  - Integration versus segregation in functional brain networks.
AB  - We propose a new methodology to evaluate the balance between segregation and
      integration in functional brain networks by using singular value decomposition
      techniques. By means of magnetoencephalography, we obtain the brain activity of a
      control group of 19 individuals during a memory task. Next, we project the node
      to-node correlations into a complex network that is analyzed from the perspective
      of its modular structure encoded in the contribution matrix. In this way, we are
      able to study the role that nodes play I/O its community and to identify
      connector and local hubs. At the mesoscale level, the analysis of the
      contribution matrix allows us to measure the degree of overlapping between
      communities and quantify how far the functional networks are from the
      configuration that better balances the integrated and segregated activity.

PMID- 21724499
TI  - Online denoising method to handle intraindividual variability of signal-to-noise
      ratio in continuous glucose monitoring.
AB  - In the last decade, the availability of new minimally invasive subcutaneous
      sensors for monitoring glucose level continuously stimulated research on new
      online strategies for improving the treatment of diabetes, including
      hyper/hypoglycemic alert generators and artificial pancreas. An important aspect
      that has to be dealt with in these applications is the random measurement noise
      that affects continuous glucose monitoring (CGM) signals. One major difficulty is
      that for a given sensor technology, the signal-to-noise ratio (SNR) can vary from
      subject to subject (interindividual variability) and also within subject
      (intraindividual variability). Recently, a denoising approach implemented through
      a Kalman filter with parameters automatically tuned, once for all, in a burn-in
      interval was proposed to cope with the interindividual variability of SNR. In
      this paper, we propose a new denoising method able to cope also with the
      intraindividual variability of the SNR. The method resorts to a Bayesian
      smoothing procedure that uses a statistically-based criterion to determine, and
      continuously update, filter parameters in real time. The performance of the
      method is assessed on both Monte Carlo simulation and 24 real CGM time series
      obtained with the Glucoday system (Menarini, Florence, Italy). The method has a
      general applicability, also outside from the CGM context.

PMID- 21724500
TI  - Measurement of lung hyperelastic properties using inverse finite element
      approach.
AB  - Hyperelastic properties of deflated lung tissue have been characterized via an
      inverse finite element approach. Such properties are useful in many medical
      diagnosis and treatment applications where tissue deformation can be modeled to
      account for during the procedure. Several indentation experiments were conducted
      on various porcine lungs' tissue specimens resected immediately from different
      regions and lobes after the animals were sacrificed. Three different strain
      energy models, namely Ogden, Yeoh, and Polynomial, were used and respective
      hyperelastic parameters were obtained. The parameters for each model were
      estimated through an optimization process where the experimental force
      displacement profiles of indentation were fitted to those obtained from finite
      element simulations performed specifically for the samples' geometries. Results
      obtained in this investigation for all the three models indicate convergence with
      reasonably low average fitting errors ranging from 2.3% to 6.2%. Independent
      tests were also performed to assess the effects of samples' heterogeneities on
      the obtained parameters. The outcome of these tests was encouraging and confirmed
      small impact of tissue inhomogeneities on the estimated parameters. The reported
      hyperelastic properties can, accordingly, pave the way for more accurate
      biomechanical modeling of the lung's soft tissue in the emerging applications of
      minimally invasive medical intervention for lung cancer diagnosis and treatment.

PMID- 21724501
TI  - MR-guided thermotherapy of abdominal organs using a robust PCA-based motion
      descriptor.
AB  - Thermotherapies can now be guided in real-time using magnetic resonance imaging
      (MRI). This technique is rapidly gaining importance in interventional therapies
      for abdominal organs such as liver and kidney. An accurate online estimation and
      characterization of organ displacement is mandatory to prevent misregistration
      and correct for motion related thermometry artifacts. In addition, when the
      ablation is performed with an extracorporal heating device such as high intensity
      focused ultrasound (HIFU), the continuous estimation of the organ displacement is
      the basis for the dynamic adjustment of the focal point position to track the
      targeted pathological tissue. In this paper, we describe the use of an optimized
      principal component analysis (PCA)-based motion descriptor to characterize in
      real-time the complex organ deformation during the therapy. The PCA was used to
      detect, in a preparative learning step, spatio-temporal coherences in the motion
      of the targeted organ. During hyperthermia, incoherent motion patterns could be
      discarded, which enabled improvements in motion estimation robustness, the
      compensation of motion related errors in thermal maps, and the adjustment of the
      beam position. The suggested method was evaluated for a moving phantom, and
      tested in vivo in the kidney and the liver of 12 healthy volunteers under free
      breathing conditions. The ability to perform a MR-guided thermotherapy in vivo
      during HIFU intervention was finally demonstrated on a porcine kidney.

PMID- 21724503
TI  - Consensus analysis of multiagent networks via aggregated and pinning approaches.
AB  - In this paper, the consensus problem of multiagent nonlinear directed networks
      (MNDNs) is discussed in the case that a MNDN does not have a spanning tree to
      reach the consensus of all nodes. By using the Lie algebra theory, a linear node
      and-node pinning method is proposed to achieve a consensus of a MNDN for all
      nonlinear functions satisfying a given set of conditions. Based on some optimal
      algorithms, large-size networks are aggregated to small-size ones. Then, by
      applying the principle minor theory to the small-size networks, a sufficient
      condition is given to reduce the number of controlled nodes. Finally, simulation
      results are given to illustrate the effectiveness of the developed criteria.

PMID- 21724502
TI  - A statistical modeling approach to the analysis of spatial patterns of FDG-PET
      uptake in human sarcoma.
AB  - Clinical experience with positron emission tomography (PET) scanning of sarcoma,
      using fluorodeoxyglucose (FDG), has established spatial heterogeneity in the
      standardized uptake values within the tumor mass as a key prognostic indicator of
      patient survival. But it may be that a more detailed quantitation of the tumor
      FDG uptake pattern could provide additional insights into risk. The present work
      develops a statistical model for this purpose. The approach is based on a tubular
      representation of the tumor mass with a simplified radial analysis of uptake,
      transverse to the tubular axis. The technique provides novel ways of
      characterizing the overall profile of the tumor, including the introduction of an
      approach for the measurement of its phase of development. The phase measure can
      distinguish between early phase tumors, in which the uptake is highest at the
      core, and later stage masses, in which there can often be central voids in FDG
      uptake. Biologically, these voids arise from necrosis and fluid, fat or cartilage
      accumulations. The tumor profiling technique is implemented using open-source
      software tools and illustrations are provided with clinically representative
      scans. A series of FDG-PET studies from 185 patients is used to formally evaluate
      the prognostic benefit. Significant   improvements in the prediction of patient
      survival and progression are obtained from the tumor profiling analysis. After
      adjustment for other factors including heterogeneity, a typical one standard
      deviation increase in phase (as determined by the analysis) is associated with
      close to 20% more risk of progression or death. The work confirms that more
      detailed quantitative assessments of the spatial pattern of PET imaging data of
      tumor masses, beyond the maximum FDG uptake  (SUV(max)) and previously considered
      measures of heterogeneity, provide improved prognostic information for potential
      input to treatment decisions for future patients.

PMID- 21724504
TI  - Practical conditions for effectiveness of the Universum learning.
AB  - Many applications of machine learning involve analysis of sparse high-dimensional
      data, in which the number of input features is larger than the number of data
      samples. Standard inductive learning methods may not be sufficient for such data,
      and this provides motivation for nonstandard learning settings. This paper
      investigates a new learning methodology called learning through contradictions or
      Universum support vector machine (U-SVM). U-SVM incorporates a priori knowledge
      about application data, in the form of additional Universum samples, into the
      learning process. This paper investigates possible advantages of U-SVM versus
      standard SVM, and describes the practical conditions necessary for the
      effectiveness of the U-SVM. These conditions are based on the analysis of the
      univariate histograms of projections of training samples onto the normal
      direction vector of (standard) SVM decision boundary. Several empirical
      comparisons are presented to illustrate the practical utility of the proposed
      approach.

PMID- 21724505
TI  - Non-negative patch alignment framework.
AB  - In this paper, we present a non-negative patch alignment framework (NPAF) to
      unify popular non-negative matrix factorization (NMF) related dimension reduction
      algorithms. It offers a new viewpoint to better understand the common property of
      different NMF algorithms. Although multiplicative update rule (MUR) can solve
      NPAF and is easy to implement, it converges slowly. Thus, we propose a fast
      gradient descent (FGD) to overcome the aforementioned problem. FGD uses the
      Newton method to search the optimal step size, and thus converges faster than
      MUR. Experiments on synthetic and real-world datasets confirm the efficiency of
      FGD compared with MUR for optimizing NPAF. Based on NPAF, we develop non-negative
      discriminative locality alignment (NDLA). Experiments on face image and
      handwritten datasets suggest the effectiveness of NDLA in classification tasks
      and its robustness to image occlusions, compared with representative NMF-related
      dimension reduction algorithms.

PMID- 21724506
TI  - Semisupervised generalized discriminant analysis.
AB  - Generalized discriminant analysis (GDA) is a commonly used method for
      dimensionality reduction. In its general form, it seeks a nonlinear projection
      that simultaneously maximizes the between-class dissimilarity and minimizes the
      within-class dissimilarity to increase class separability. In real-world
      applications where labeled data are scarce, GDA may not work very well. However,
      unlabeled data are often available in large quantities at very low cost. In this
      paper, we propose a novel GDA algorithm which is abbreviated as semisupervised
      generalized discriminant analysis (SSGDA). We utilize unlabeled data to maximize
      an optimality criterion of GDA and formulate the problem as an optimization
      problem that is solved using the constrained concave-convex procedure. The
      optimization procedure leads to estimation of the class labels for the unlabeled
      data. We propose a novel confidence measure and a method for selecting those
      unlabeled data points whose labels are estimated with high confidence. The
      selected unlabeled data can then be used to augment the original labeled dataset
      for performing GDA. We also propose a variant of SSGDA, called M-SSGDA, which
      adopts the manifold assumption to utilize the unlabeled data. Extensive
      experiments on many benchmark datasets demonstrate the effectiveness of our
      proposed methods.

PMID- 21724507
TI  - k-NS: a classifier by the distance to the nearest subspace.
AB  - To improve the classification performance of k-NN, this paper presents a
      classifier, called k -NS, based on the Euclidian distances from a query sample to
      the nearest subspaces. Each nearest subspace is spanned by k nearest samples of a
      same class. A simple discriminant is derived to calculate the distances due to
      the geometric meaning of the Grammian, and the calculation stability of the
      discriminant is guaranteed by embedding Tikhonov regularization. The proposed
      classifier, k-NS, categorizes a query sample into the class whose corresponding
      subspace is proximal. Because the Grammian only involves inner products, the
      classifier is naturally extended into the high-dimensional feature space induced
      by kernel functions. The experimental results on 13 publicly available benchmark
      datasets show that k-NS is quite promising compared to several other classifiers
      founded on nearest neighbors in terms of training and test accuracy and
      efficiency.

PMID- 21724508
TI  - A psychovisual quality metric in free-energy principle.
AB  - In this paper, we propose a new psychovisual quality metric of images based on
      recent developments in brain theory and neuroscience, particularly the free
      energy principle. The perception and understanding of an image is modeled as an
      active inference process, in which the brain tries to explain the scene using an
      internal generative model. The psychovisual quality is thus closely related to
      how accurately visual sensory data can be explained by the generative model, and
      the upper bound of the discrepancy between the image signal and its best internal
      description is given by the free energy of the cognition process. Therefore, the
      perceptual quality of an image can be quantified using the free energy.
      Constructively, we develop a reduced-reference free-energy-based distortion
      metric (FEDM) and a no-reference free-energy-based quality metric (NFEQM). The
      FEDM and the NFEQM are nearly invariant to many global systematic deviations in
      geometry and illumination that hardly affect visual quality, for which existing
      image quality metrics wrongly predict severe quality degradation. Although with
      very limited or even without information on the reference image, the FEDM and the
      NFEQM are highly competitive compared with the full-reference SSIM image quality
      metric on images in the popular LIVE database. Moreover, FEDM and NFEQM can
      measure correctly the visual quality of some model-based image processing
      algorithms, for which the competing metrics often contradict with viewers'
      opinions.

PMID- 21724509
TI  - Efficient registration of nonrigid 3-D bodies.
AB  - We present a novel method to perform an accurate registration of 3-D nonrigid
      bodies by using phase-shift properties of the dual-tree complex wavelet transform
      [Formula: see text]. Since the phases of  [Formula: see text] coefficients change
      approximately linearly with the amount of feature displacement in the spatial
      domain, motion can be estimated using the phase information from these
      coefficients. The motion estimation is performed iteratively: first by using
      coarser level complex coefficients to determine large motion components and then
      by employing finer level coefficients to refine the motion field. We use a
      parametric affine model to describe the motion, where the affine parameters are
      found locally by substituting into an optical flow model and by solving the
      resulting overdetermined set of equations. From the estimated affine parameters,
      the motion field between the sensed and the reference data sets can be generated,
      and the sensed data set then can be shifted and interpolated spatially to align
      with the reference data set.

PMID- 21724510
TI  - Coupled bias-variance tradeoff for cross-pose face recognition.
AB  - Subspace-based face representation can be looked as a regression problem. From
      this viewpoint, we first revisited the problem of recognizing faces across pose
      differences, which is a bottleneck in face recognition. Then, we propose a new
      approach for cross-pose face recognition using a regressor with a coupled bias
      variance tradeoff. We found that striking a coupled balance between bias and
      variance in regression for different poses could improve the regressor-based
      cross-pose face representation, i.e., the regressor can be more stable against a
      pose difference. With the basic idea, ridge regression and lasso regression are
      explored. Experimental results on CMU PIE, the FERET, and the Multi-PIE face
      databases show that the proposed bias-variance tradeoff can achieve considerable
      reinforcement in recognition performance.

PMID- 21724511
TI  - Human gait recognition using patch distribution feature and locality-constrained
      group sparse representation.
AB  - In this paper, we propose a new patch distribution feature (PDF) (i.e., referred
      to as Gabor-PDF) for human gait recognition. We represent each gait energy image
      (GEI) as a set of local augmented Gabor features, which concatenate the Gabor
      features extracted from different scales and different orientations together with
      the X-Y coordinates. We learn a global Gaussian mixture model (GMM) (i.e.,
      referred to as the universal background model) with the local augmented Gabor
      features from all the gallery GEIs; then, each gallery or probe GEI is further
      expressed as the normalized parameters of an image-specific GMM adapted from the
      global GMM. Observing that one video is naturally represented as a group of GEIs,
      we also propose a new classification method called locality-constrained group
      sparse representation (LGSR) to classify each probe video by minimizing the
      weighted  l(1, 2) mixed-norm-regularized reconstruction error with respect to the
      gallery videos. In contrast to the standard group sparse representation method
      that is a special case of LGSR, the group sparsity and local smooth sparsity
      constraints are both enforced in LGSR. Our comprehensive experiments on the
      benchmark USF HumanID database demonstrate the effectiveness of the newly
      proposed feature Gabor-PDF and the new classification method LGSR for human gait
      recognition. Moreover, LGSR using the new feature Gabor-PDF achieves the best
      average Rank-1 and Rank-5 recognition rates on this database among all gait
      recognition algorithms proposed to date.

PMID- 21724512
TI  - Iterative narrowband-based graph cuts optimization for geodesic active contours
      with region forces (GACWRF).
AB  - In this paper, an iterative narrow-band-based graph cuts (INBBGC) method is
      proposed to optimize the geodesic active contours with region forces (GACWRF)
      model for interactive object segmentation. Based on cut metric on graphs proposed
      by Boykov and Kolmogorov, an NBBGC method is devised to compute the local
      minimization of GAC. An extension to an iterative manner, namely, INBBGC, is
      developed for less sensitivity to the initial curve. The INBBGC method is similar
      to graph-cuts-based active contour (GCBAC) presented by Xu , and their
      differences have been analyzed and discussed. We then integrate the region force
      into GAC. An improved INBBGC (IINBBGC) method is proposed to optimize the GACWRF
      model, thus can effectively deal with the concave region and complicated real
      world images segmentation. Two region force models such as mean and probability
      models are studied. Therefore, the GCBAC method can be regarded as the special
      case of our proposed IINBBGC method without region force. Our proposed algorithm
      has been also analyzed to be similar to the Grabcut method when the Gaussian
      mixture model region force is adopted, and the band region is extended to the
      whole image. Thus, our proposed IINBBGC method can be regarded as narrow-band
      based Grabcut method or GCBAC with region force method. We apply our proposed
      IINBBGC algorithm on synthetic and real-world images to emphasize its
      performance, compared with other segmentation methods, such as GCBAC and Grabcut
      methods.

PMID- 21724513
TI  - Three-dimensional deformable-model-based localization and recognition of road
      vehicles.
AB  - We address the problem of model-based object recognition. Our aim is to localize
      and recognize road vehicles from monocular images or videos in calibrated traffic
      scenes. A 3-D deformable vehicle model with 12 shape parameters is set up as
      prior information, and its pose is determined by three parameters, which are its
      position on the ground plane and its orientation about the vertical axis under
      ground-plane constraints. An efficient local gradient-based method is proposed to
      evaluate the fitness between the projection of the vehicle model and image data,
      which is combined into a novel evolutionary computing framework to estimate the
      12 shape parameters and three pose parameters by iterative evolution. The
      recovery of pose parameters achieves vehicle localization, whereas the shape
      parameters are used for vehicle recognition. Numerous experiments are conducted
      in this paper to demonstrate the performance of our approach. It is shown that
      the local gradient-based method can evaluate accurately and efficiently the
      fitness between the projection of the vehicle model and the image data. The
      evolutionary computing framework is effective for vehicles of different types and
      poses is robust to all kinds of occlusion.

PMID- 21724514
TI  - Multiple exposure fusion for high dynamic range image acquisition.
AB  - A multiple exposure fusion to enhance the dynamic range of an image is proposed.
      The construction of high dynamic range images (HDRIs) is performed by combining
      multiple images taken with different exposures and estimating the irradiance
      value for each pixel. This is a common process for HDRI acquisition. During this
      process, displacements of the images caused by object movements often yield
      motion blur and ghosting artifacts. To address the problem, this paper presents
      an efficient and accurate multiple exposure fusion technique for the HDRI
      acquisition. Our method simultaneously estimates displacements and occlusion and
      saturation regions by using maximum a posteriori estimation and constructs motion
      blur-free HDRIs. We also propose a new weighting scheme for the multiple image
      fusion. We demonstrate that our HDRI acquisition algorithm is accurate, even for
      images with large motion.

PMID- 21724515
TI  - Confidence About Possible Explanations.
AB  - We revise the notion of confidence with which we estimate the parameters of a
      given distribution law in terms of their compatibility with the sample we have
      observed. This is a recent perspective that allows us to get a more intuitive
      feeling of the crucial concept of the confidence interval in parametric inference
      together with quick tools for exactly computing them even in conditions far from
      the common Gaussian framework where standard methods fail. The key artifact
      consists of working with a representation of the compatible parameters in terms
      of random variables without priors. This leads to new estimators that meet the
      most demanding requirements of the modern statistical inference in terms of
      learning algorithms. We support our methods with: a consistent theoretical
      framework, general-purpose estimation procedures, and a set of paradigmatic
      benchmarks. 

PMID- 21724516
TI  - A Greedy Algorithm for Faster Feasibility Evaluation of All-Terminal-Reliable
      Networks.
AB  - Although calculating the all-terminal reliability (ATR) of a stochastic network
      is a computationally expensive task, deciding whether the ATR is greater than a
      preset value could be done with less effort. This study proposes a new method
      that generates the sequential lower and upper bounds of the ATR, based on greedy
      network factoring. The proposed method begins by finding the most reliable
      spanning tree and most unreliable cut set in the given network. Their operative
      and failing probabilities are used to update the lower and upper bounds of the
      ATR. Subnetworks are then produced, corresponding to each state of the spanning
      tree or cut set. This procedure is applied to the subnetworks in a recursive
      manner to update the ATR bounds further, until either the lower or upper bound
      reaches the preset ATR requirement. Due to the rapid convergence of the ATR
      bounds, the feasibility of a given network is likely to be decided at an early
      stage of the network factoring process. This study proposes several different
      implementations of the greedy algorithm and introduces the results of the
      computer experiments comparing them. Based on the experimental results, this
      study suggests a relationship between the performance of each implementation and
      the characteristics of the given network, such as layout and edge operating
      probabilities. 

PMID- 21724517
TI  - Using Ant Programming Guided by Grammar for Building Rule-Based Classifiers.
AB  - The extraction of comprehensible knowledge is one of the major challenges in many
      domains. In this paper, an ant programming (AP) framework, which is capable of
      mining classification rules easily comprehensible by humans, and, therefore,
      capable of supporting expert-domain decisions, is presented. The algorithm
      proposed, called grammar based ant programming (GBAP), is the first AP algorithm
      developed for the extraction of classification rules, and it is guided by a
      context-free grammar that ensures the creation of new valid individuals. To
      compute the transition probability of each available movement, this new model
      introduces the use of two complementary heuristic functions, instead of just one,
      as typical ant-based algorithms do. The selection of a consequent for each rule
      mined and the selection of the rules that make up the classifier are based on the
      use of a niching approach. The performance of GBAP is compared against other
      classification techniques on 18 varied data sets. Experimental results show that
      our approach produces comprehensible rules and competitive or better accuracy
      values than those achieved by the other classification algorithms compared with
      it. 

PMID- 21724518
TI  - Tracking With a Hierarchical Partitioned Particle Filter and Movement Modelling.
AB  - We present an approach to track human subjects using an articulated human
      framework. First, we describe the articulated hierarchical human model. Second,
      we develop a stochastic hierarchical, partitioned, particle filter based on the
      natural structure and limb dependency of the human body. We apply this to track
      human subjects in video sequences using likelihoods adapted to the hierarchical
      process. Finally, we evaluate the effectiveness of the described approach using
      publicly available datasets. 

PMID- 21724519
TI  - A Learning Algorithm for Multimodal Grammar Inference.
AB  - The high costs of development and maintenance of multimodal grammars in
      integrating and understanding input in multimodal interfaces lead to the
      investigation of novel algorithmic solutions in automating grammar generation and
      in updating processes. Many algorithms for context-free grammar inference have
      been developed in the natural language processing literature. An extension of
      these algorithms toward the inference of multimodal grammars is necessary for
      multimodal input processing. In this paper, we propose a novel grammar inference
      mechanism that allows us to learn a multimodal grammar from its positive samples
      of multimodal sentences. The algorithm first generates the multimodal grammar
      that is able to parse the positive samples of sentences and, afterward, makes use
      of two learning operators and the minimum description length metrics in improving
      the grammar description and in avoiding the over-generalization problem. The
      experimental results highlight the acceptable performances of the algorithm
      proposed in this paper since it has a very high probability of parsing valid
      sentences. 

PMID- 21724520
TI  - Quasi-static modeling of human limb for intra-body communications with
      experiments.
AB  - In recent years, the increasing number of wearable devices on human has been
      witnessed as a trend. These devices can serve for many purposes: personal
      entertainment, communication, emergency mission, health care supervision,
      delivery, etc. Sharing information among the devices scattered across the human
      body requires a body area network (BAN) and body sensor network (BSN). However,
      implementation of the BAN/BSN with the conventional wireless technologies cannot
      give optimal result. It is mainly because the high requirements of light weight,
      miniature, energy efficiency, security, and less electromagnetic interference
      greatly limit the resources available for the communication modules. The newly
      developed intra-body communication (IBC) can alleviate most of the mentioned
      problems. This technique, which employs the human body as a communication
      channel, could be an innovative networking method for sensors and devices on the
      human body. In order to encourage the research and development of the IBC, the
      authors are favorable to lay a better and more formal theoretical foundation on
      IBC. They propose a multilayer mathematical model using volume conductor theory
      for galvanic coupling IBC on a human limb with consideration on the inhomogeneous
      properties of human tissue. By introducing and checking with quasi-static
      approximation criteria, Maxwell's equations are decoupled and capacitance effect
      is included to the governing equation for further improvement. Finally, the
      accuracy and potential of the model are examined from both in vitro and in vivo
      experimental results.

PMID- 21724521
TI  - Glutamatergic neurons in rodent models respond to nanoscale particulate urban air
      pollutants in vivo and in vitro.
AB  - BACKGROUND: Inhalation of airborne particulate matter (PM) derived from urban
      traffic is associated with pathology in the arteries, heart, and lung; effects on
      brain are also indicated but are less documented. OBJECTIVE: We evaluated rodent
      brain responses to urban nanoscale (< 200 nm) PM (nPM). METHODS: Ambient nPM
      collected near an urban freeway was transferred to aqueous suspension and
      reaerosolized for 10-week inhalation exposure of mice or directly applied to rat
      brain cell cultures. RESULTS: Free radicals were detected by electron
      paramagnetic resonance in the nPM 30 days after initial collection. Chronic
      inhalation of reaerosolized nPM altered selected neuronal and glial activities in
      mice. The neuronal glutamate receptor subunit (GluA1) was decreased in
      hippocampus, whereas glia were activated and inflammatory cytokines were induced
      [interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNFalpha)] in
      cerebral cortex. Two in vitro models showed effects of nPM suspensions within 24
      48 hr of exposure that involved glutamatergic functions. In hippocampal slice
      cultures, nPM increased the neurotoxicity of NMDA (N-methyl-d-aspartic acid), a
      glutamatergic agonist, which was in turn blocked by the NMDA antagonist AP5 [(2R)
      amino-5-phosphonopentanoate]. In embryonic neuron cultures, nPM impaired neurite
      outgrowth, also blocked by AP5. Induction of IL-1alpha and TNFalpha in mixed glia
      cultures required higher nPM concentrations than did neuronal effects. Because
      conditioned media from nPM-exposed glia also impaired outgrowth of embryonic
      neurites, nPM can act indirectly, as well as directly, on neurons in vitro.
      CONCLUSIONS: nPM can affect embryonic and adult neurons through glutamatergic
      mechanisms. The interactions of nPM with glutamatergic neuronal functions suggest
      that cerebral ischemia, which involves glutamatergic excitotoxicity, could be
      exacerbated by nPM.

PMID- 21724522
TI  - Indoor air pollution and blood pressure in adult women living in rural China.
AB  - BACKGROUND: Almost half of the world's population uses coal and biomass fuels for
      domestic energy. Limited evidence suggests that exposure to air pollutants from
      indoor biomass combustion may be associated with elevated blood pressure (BP).
      OBJECTIVE: Our aim was to assess the relationship between air pollution exposure
      from indoor biomass combustion and BP in women in rural China. METHODS: We
      measured 24-hr personal integrated gravimetric exposure to fine particles < 2.5
      um in aerodynamic diameter (PM2.5) and systolic BP (SBP) and diastolic BP (DBP)
      in the winter and summer among 280 women >= 25 years of age living in rural
      households using biomass fuels in Yunnan, China. We investigated the association
      between PM2.5 exposure and SBP and DBP using mixed-effects models with random
      intercepts to account for correlation among repeated measures. RESULTS: Personal
      average 24-hr exposure to PM2.5 ranged from 22 to 634 ug/m3 in winter and from 9
      to 492 ug/m3 in summer. A 1-log-ug/m3 increase in PM2.5 exposure was associated
      with 2.2 mm Hg higher SBP [95% confidence interval (CI), 0.8 to 3.7; p = 0.003]
      and 0.5 mm Hg higher DBP (95% CI, -0.4 to 1.3; p = 0.31) among all women;
      estimated effects varied by age group. Among women > 50 years of age, a 1-log
      ug/m3 increase in PM2.5 exposure was associated with 4.1 mm Hg higher SBP (95%
      CI, 1.5 to 6.6; p = 0.002) and 1.8 mm Hg higher DBP (95% CI, 0.4 to 3.2; p =
      0.01). PM2.5 exposure was positively associated with SBP among younger women, but
      the association was not statistically significant. CONCLUSION: PM2.5 exposure
      from biomass combustion may be a risk factor for elevated BP and hence for
      cardiovascular events. Our findings should be corroborated in longitudinal
      studies.

PMID- 21724523
TI  - Mutations in EGFR signal pathway in correlation with response to treatment of
      head and neck cancers.
AB  - The prognostic and predictive value of the epidermal growth factor receptor
      (EGFR) expression and some genetic alterations in an EGFR signal pathway, such as
      the EGFR amplification, the EGFR activating tyrosine kinase domain mutations or
      the k-ras gene mutation were investigated in our study. The aim of the research
      was to evaluate the occurrence of the above-mentioned biomarkers in correlation
      with a therapeutic response and survival in patients with locoregionally advanced
      spinocellular head and neck cancers. KEYWORDS: Head and neck cancer, EGFR,
      predictive marker, k-ras, EGFR amplification, EGFR tyrosine kinase domain
      mutation.

PMID- 21724524
TI  - Comparison of IMRT and Rapidarc treatment plans using AAPM task group test
      suites.
AB  - The purpose of this study is to examine the plan quality and monitor unit with
      sliding window IMRT and RapidArc (RA) treatment plans using American Association
      Physicists in Medicine TG119 test suite DICOM-RT images and structure sets. The
      structure set includes multi-target (superior, central, inferior), prostate, head
      and neck and C-shape. Plans were performed with Eclipse planning system using AAA
      algorithm with the plan goals specified in TG119. The plan results for
      multitarget shows that the D99 is greater than the plan goal for all the targets.
      The D10 is less than the plan goal for superior and inferior targets in both IMRT
      and RA plans. The D10 is 5% more with IMRT plan and 7% more with RA plan for
      central target in comparison with plan goal. The plan results for prostate shows
      that D95 is greater than the plan goal for both IMRT and RA plans. The D5 is less
      than the plan goal for IMRT plan and almost equal to plan goal for RA plan. The
      D30 is less than the plan goal for bladder and rectum in both the plans. The D10
      is higher than the plan goal by 1.9% and 2.5% in IMRT and RA plan for rectum. The
      plan results for head and neck shows that the D99 and D90 were greater than the
      plan goal for PTV. The spinal cord and parotid doses were less than the plan goal
      in both the plans. The plan results for C-shape shows that the D95 was greater
      than the plan goal and D10 was less than the plan goal for PTV. The dose to
      central core was less than the plan goal in both IMRT and RA plans. Both the IMRT
      and RapidArc plans have met the plan goal for all the target and normal
      structures. RapidArc optimization and treatment planning requires more time than
      the IMRT plan. The monitor unit calculated by the RapidArc plan is less compared
      to IMRT plan, which reduces the treatment error caused by patient motion during
      treatment and integral dose.

PMID- 21724525
TI  - Clinical significance of hTERC and C-Myc genes amplification in a group of
      Egyptian patients with cancer cervix.
AB  - BACKGROUND: Cervical cancer is the second most common cancer in women worldwide
      after breast cancer. Cervical cancer is a preventable disease. The implementation
      of cervical cancer screening programs has greatly decreased the morbidity and
      mortality, as precancerous lesions and early invasive cervical cancer could be
      detected and treated effectively. The detection of hTERC gene amplification was
      suggested as a possible diagnostic marker for use in routine cytological
      screening. OBJECTIVES: The present study was designed to detect genomic gains of
      the hTERC and C-MYC genes using FISH technique and to investigate the
      relationship between genes amplification and the clinical data of the patients.
      PATIENTS AND METHODS: The current study was carried out on twelve cases with
      cervical cancer at different grades (three cases were grade I, six cases were
      grade II and three cases were grade III). Interphase FISH analysis using LSI
      probe, Cervical Cancer probe hTERC (3q26) & C-MYC (8q24), was successfully
      performed on 12 patients with cancer cervix. RESULTS: Interphase FISH analysis
      revealed positive hTERC gene amplification in all cases of cancer cervix (100%).
      However C-MYC gene amplification was detected in four cases only (33.3%).
      Statistical analysis of the data revealed significant correlation between hTERC
      amplification and grading. Also, there was significant correlation between C-MYC
      amplification and grading and highly significant correlation between C-MYC
      amplification and hTERC amplification. On the other hand hTERC and C-MYC genes
      amplification showed an inverse correlation with the ages of the patients.
      CONCLUSION: The present study highlights the importance of using hTERC and C-MYC
      genes FISH probes for cases with cancer cervix or pre-malignant lesions as a
      sensitive technique. This method provides an easy and effective applicable
      approach which helps in the diagnosis and prognosis, as an increased copy number
      is associated with a more advanced grade that could be detected in the early
      stages of the disease.

PMID- 21724526
TI  - Disease profile and treatment results of anal canal SCC: experience from AIIMS,
      New Delhi.
AB  - INTRODUCTION: Anal Canal squamous cell carcinoma (SCC) accounts for nearly 2% of
      all cancers of the alimentary tract. Over the past few years, the management of
      anal canal cancer has changed from primary surgery to primary chemo-radiotherapy
      (CRT). METHODS: A total of 83 patients' (pts) records (62 males, 21 females) were
      retrospectively reviewed. Length of disease was <5 cm in 44 pts and confined to
      primary in 46 pts. Ten pts have anti-cancer therapy outside. We delivered
      radiotherapy (RT) alone to 16 pts, chemotherapy (CT) alone to 4 pts, CRT in 51
      pts and pre-operative (pre-op) RT in 2 pts. RT dose was up to 30 Gray (Gy) =16;
      30-50 Gy=12 and >50 Gy=41 pts. RESULTS: RT compliance was optimal in 64/69, grade
      (Gr) <= 2 toxicity in 56/69 and Gr >= 2 in 13/69 pts. Thirteen pts (18.84%) were
      hospitalized during RT. No response (NR) was found in 4/83, <50% in 18/83, >50
      <100% in 39/83 and complete response (CR) in 22/83 pts. Recurrence at primary
      site was seen in 7 and loco-regional in 2 pts. Salvage therapy was done in all 9
      pts (surgery=8 and CT=1). Status at last follow up, alive without disease = 22/83
      and with disease = 61/83 pts. CONCLUSION: This retrospective analysis revealed
      that the advanced disease was in 47%, the optimal anti-cancer therapy could be
      delivered to 63.9%. Despite heterogeneity of patient population and management,
      the overall disease-free survival (DFS) with sphincter-preservation was achieved
      in 26.5% pts.

PMID- 21724527
TI  - Prediction of anthracycline induced cardiotoxicity: study of thirty-one Iraqi
      adult patients.
AB  - OBJECTIVE: To look for a nearly ideal tool for prediction of anthracycline
      induced cardiotoxicity. METHOD: Thirty-one patients with various hematological
      malignancies were included in the study which was conducted from Sept. 2005 to
      Sept. 2006 in Baghdad Teaching Hospital - Hematology Unit. Initial cardiovascular
      assessment including cardiac troponin I, electrocardiography and echocardiography
      were done and repeated one month after the commencement of anthracycline-based
      regimen. Cardiotoxicity was considered present if the patient has clinical and
      electrocardiographic evidences, troponin positivity, echocardiographic evidence,
      or any combination of these. RESULTS: The mean age for the study sample was 34.1
      +/- 17.2 years comprising of 17 male and 14 female patients. Increasing age, body
      surface area, anthracycline dose as well as the concomitant use of
      cyclophosphomide/All Trans Retinoic Acid were associated with increased risk of
      cardiotoxicity. The cut-off point of body surface area above which the risk of
      anthracycline-induced cardiotoxicity is increased was 1.88 m2 while the cut-off
      point for anthracyclines dose was 145.5 mg/m2. The constellation of clinical
      data, ECG, and cTnI was 92% predictive of early evidence of anthracycline-induced
      cardiotoxicity. More weight is added when echocardiography is used as a
      diagnostic tool. The incidence of cardiotoxicity attributed to treatment was
      38.7%. The predictive power of cardiac troponin I alone was 58.3%, whereas it
      increases to 91% when combined with electrocardiography and to 95% when combined
      with echocardiographic study. CONCLUSION: The age, anthracyclines dose and the
      use of other chemotherapeutics increase the risk of anthracycline-induced
      cardiotoxicity. Cardiac troponin I is a simple non-invasive indicator for the
      presence of anthracycline-induced cardiotoxicity especially when used in
      combination with other parameters.

PMID- 21724528
TI  - Early gastrointestinal complications of stem cell transplant - results of
      prospective study at IRCH, AIIMS, India.
AB  - BACKGROUND: The study was conducted with the purpose of finding clinical profile
      of early gastrointestinal complications of stem cell transplant at this center.
      METHODS: 70 consecutive subjects, who were subject to bone marrow transplant from
      October 2002 to September 2004, were prospectively studied. The gastrointestinal
      complications were followed in first 100 days of transplant and recorded in a pre
      determined format. RESULTS: Study population comprised of 23 allo-transplant
      (with 3-non-myelablative procedures) and 47 auto-transplant subjects.
      Gastrointestinal complications included: nausea and vomiting in 19 (82.60%),
      mucositis- 20 (86.95%), diarrhea- 15 (65.21%), veno-occlusive disease (VOD) - 3
      (13.04%) and acute pancreatitis- 1 (4.34%) in allo-transplant group. Nausea and
      vomiting occurred 36 (76.59%), mucositis- 46 (97.88%) diarrhea- 39 (82.98%), VOD-
      5 (10.64%) in auto- transplant subjects. Acute graft versus host disease (AGVHD)
      involved gut in 3 and liver in 1 case of allo-BMT-group.

PMID- 21724529
TI  - Medullary carcinoma of the breast: ten year clinical experience of the Kuwait
      cancer control centre.
AB  - BACKGROUND: Medullary carcinomas of the breast account for fewer than 7% of all
      invasive breast cancers. Some investigators include medullary carcinomas in the
      favourable histologic subtype, despite its aggressive histologic appearance.
      However, others fail to confirm its favourable prognosis. METHODS: This was a
      retrospective analysis of sixty-one (61) cases of breast cancer cases diagnosed
      with Medullary Carcinoma, presenting to the Kuwait Cancer Control Center between
      1995 and 2005. RESULTS: Median survival time was 122 months and the seven-year
      disease free survival was 82%. Overall survival rate was not assessed as no cases
      died during the study period. No cases were metastatic from the start and only
      eight cases developed metastases, local recurrence or contralateral breast
      primary. 68.8% of the cases were Stage I or IIA (i.e. no lymph node affection).
      CONCLUSION: There is no overt favourable prognosis of medullary carcinoma when
      compared to invasive ductal carcinoma. Prognosis is more related to stage than
      histologic subtyping. The majority of cases were negative estrogen and
      progesterone receptor status and node negative.

PMID- 21724530
TI  - Respiratory gated simultaneous integrated boost-intensity modulated radiotherapy
      (SIB-IMRT) after breast conservative surgery for carcinoma of the breast: The
      Salmaniya Medical complex experience.
AB  - PURPOSE: To present our clinical experience using SIB-IMRT Technique for Intact
      Breast cancer. MATERIALS AND METHODS: A retrospective review of 45 cases of Stage
      I-IV breast cancer patients treated with SIB-IMRT with respiratory gating after
      Conservative treatments from 25th November 2008 to 16th February 2010. The most
      common fractionation was 1.8 Gy to Ipsilateral Breast tissue and 2.2 Gy to the
      lumpectomy cavity giving whole breast dose as 50.4 Gy and Lumpectomy cavity dose
      as 61.6 Gy over 28 fractions concomitantly. Respiratory gating was done and CT
      images were taken in inspiratory breath hold position. RESULTS: A total of 45
      patients with breast cancer - stage I (17.7%), II (71%), III (8.9%), IV (2.2%)
      were treated with SIB- IMRT with respiratory gated radiotherapy. Out of 45
      patients, 24 are of left sided breast cancer and 21 are of right sided breast
      cancer patients. The median, Dose maximum (D-max) in SIB-IMRT is 106.2% of
      prescribed lumpectomy site dose. The median isodose line prescribed to PTV-2 is
      100%. The Conformity index (CI) is 0.9688 (median value) and Homogeneity index
      (HI) 1.06 (median). The median ipsilateral lung, mean dose is 21.66 Gy and V-20
      is 37.4%. For left sided cases the median value of mean heart dose, V-30 and V-40
      are 22.98 Gy, 23.45% and 9.45 % respectively. Acute skin toxicity was of Grade-I
      in 2.2 %, Grade-II in 64.4 %, Grade-III in 31.1 %, and Grade-IV in 2.2 %. The
      global Breast cosmoses were seen excellent in majority (93%) of case at median
      follow up of 8 months duration. CONCLUSIONS: Breast SIB-IMRT Technique is
      feasible and comparable with other treatment techniques with reduced treatment
      duration by six fractions. At median follow up of 8 months the skin toxicity and
      cosmoses are excellent in high percentage of cases.

PMID- 21724531
TI  - Case report and review of literature: temporary asymptomatic sinus bradycardia
      with carboplatin, paclitaxel and bevacizumab: under-reported in clinical trials
      and under-disclosed in practice.
AB  - INTRODUCTION: Paclitaxel, Carboplatin, and Bevacizumab (PCB) is one of the
      standard chemotherapy regimens for the treatment of non-small cell lung cancer.
      Temporary asymptomatic bradycardia is recognized toxicity of paclitaxel. However,
      it is under-disclosed to patients during consent for treatment and is under
      reported in clinical phase III trials. CASE REPORT: Here, we report a case of
      severe but temporary asymptomatic sinus bradycardia (heart rate 39 bpm) in a
      patient immediately after receiving PCB. The patient was not informed of this
      risk during consent to therapy leading to non-compliance with future plan of
      management. Literature search showed that bradycardia is documented. However, it
      is not reported adequately in land mark phase III trials' reports. CONCLUSION:
      The cause of bradycardia in this patient is probably paclitaxel. Oncologists
      should disclose this potential risk to patients during consent to chemotherapy.
      Investigators should monitor and report it when conducting land mark trials.

PMID- 21724532
TI  - Verruciform xanthoma of the penis in a young male masquerading as squamous cell
      carcinoma: case report.
AB  - Verruciform xanthoma (VX) is a relatively rare benign lesion of unknown etiology
      with a predilection for oral mucosa. Penis is an uncommon location and to date
      only 17 cases of VX of penis have been reported. The lesion assumes importance as
      it can be easily mistaken for verrucous carcinoma or squamous cell carcinoma. We
      present herein a case of penile VX in a 25-year-old man who was referred to our
      institute with a histopathologic diagnosis of squamous cell carcinoma reported
      elsewhere. On microscopy the lesion demonstrated florid verruciform hyperplasia
      of the epidermis with hyperkeratosis, parakeratosis and acanthosis. There was a
      dense infiltrate of foam cells in the papillary dermis (a hallmark of VX), which
      were positive for CD68 and negative for S-100 protein. We present this case to
      highlight the significance of recognizing VX in extra oral location. An awareness
      of this entity is crucial to prevent misdiagnosis and halt inappropriate
      therapeutic intervention.

PMID- 21724533
TI  - Acute respiratory distress syndrome in poor prognostic germ cell tumor with
      multiple lung metastases: a case report.
AB  - We report a case which is unique as this patient was diagnosed pathologically as
      adenocarcinoma of the endometrium but clinically progressed as germ cell tumor.
      This was evident by progressive and rapid raised tumor markers (BHCG & LDH) with
      the development of multiple bilateral lung metastases. She was treated by
      administrating low doses of systemic combination chemotherapy as per the
      literature. Unfortunately, she developed acute respiratory distress syndrome as
      the complication of treatment and died due to it.

PMID- 21724534
TI  - The clinical significance of anti-Mullerian hormone evaluation in gynecological
      endocrinology.
AB  - Anti-Mullerian hormone (AMH) is a homodimeric glycoprotein, a member of the
      transforming growth factor-beta superfamily. Over the last decade, a large number
      of studies examining the multiple roles of AMH have been published. AMH levels
      accurately reflect the ovarian follicular reserve and could, therefore, be
      considered as an extremely sensitive marker of ovarian aging and a valuable tool
      in the diagnosis and the recognition of recurrence of granulosa cell tumors.
      Furthermore, AMH evaluation is of clinical importance in predicting the success
      of in vitro fertilization (IVF). Additionally, AMH could be a surrogate
      diagnostic marker of polycystic ovary syndrome in cases in which ultrasonographic
      examination is not possible. This article is a review of the clinical usefulness
      of AMH evaluation in the fields of gynecological endocrinology, menopause,
      gynecological oncology and assisted reproduction. Special reference is made to
      the possible implications of AMH in the pathogenesis of polycystic ovary syndrome
      and the relationship between AMH and obesity.

PMID- 21724535
TI  - Menstrual function in sports.
AB  - OBJECTIVE: To highlight the recent developments in the field of menstrual
      function in sports and to provide an overview of our current understanding in
      regard to the pathophysiology, evaluation and management strategies of exercise
      related reproductive dysfunction. DESIGN: A PUBMED search was carried out and all
      articles published from 1980 to 2010 with title words related to exercise,
      athletes, menstrual function and primary and secondary amenorrhea were reviewed.
      The review structure includes a pathophysiology overview, menstrual dysfunction
      among different athletic disciplines, clinical manifestations, evaluation and
      management strategies, with particular emphasis on recent data regarding the use
      of oral contraceptives and hormone replacement therapy. RESULTS AND CONCLUSION:
      Exercise-related reproductive dysfunction appears to be multifactorial in origin
      and remains a diagnosis of exclusion. Recent findings underscore the endocrine
      role of adipose tissue in the regulation of metabolism and reproduction,
      providing further data on our understanding of the pathophysiology of exercise
      related reproductive dysfunction. Clinical manifestations range from primary
      amenorrhea or delayed menarche to luteal phase deficiency, oligomenorrhea,
      anovulation and secondary amenorrhea. Amenorrhea constitutes the most serious
      clinical consequence and is associated with bone pathology. Early diagnosis,
      thorough evaluation and individualized management (ranging from diet and
      exercise, or behavior adjustments to pharmacologic treatment) should be achieved
      in order to preserve bone mass.

PMID- 21724536
TI  - Thyroid function during critical illness.
AB  - The metabolic support of the critically ill patient is a relatively new target of
      active research and little is as yet known about the effects of critical illness
      on metabolism. The nonthyroidal illness syndrome, also known as the low T3
      syndrome or euthyroid sick syndrome, describes a condition characterized by
      abnormal thyroid function tests encountered in patients with acute or chronic
      systemic illnesses. The laboratory parameters of this syndrome include low serum
      levels of triiodothyronine (T3) and high levels of reverse T3, with normal or low
      levels of thyroxine (T4) and normal or low levels of thyroid-stimulating hormone
      (TSH). This condition may affect 60 to 70% of critically ill patients. The
      changes in serum thyroid hormone levels in the critically ill patient seem to
      result from alterations in the peripheral metabolism of the thyroid hormones, in
      TSH regulation, in the binding of thyroid hormone to transport-protein and in
      receptor binding and intracellular uptake. Medications also have a very important
      role in these alterations. Hormonal changes can be seen within the first hours of
      critical illness and, interestingly, these changes correlate with final outcome.
      Data on the beneficial effect of thyroid hormone treatment on outcome in
      critically ill patients are so far controversial. Thyroid function generally
      returns to normal as the acute illness resolves.

PMID- 21724537
TI  - Combined strength and aerobic training increases transforming growth factor-beta1
      in patients with type 2 diabetes.
AB  - OBJECTIVE: The aim of the present study was to examine the effects of a combined
      strength and aerobic training program on pro- and anti-inflammatory cytokines and
      transforming growth factor-beta1 in patients with type 2 diabetes. DESIGN: Ten
      patients with type 2 diabetes, aged 55.5 (5) years [median (IQR)] participated in
      a supervised systematic exercise training program which included aerobic exercise
      and strength training, undertaken four days per week for eight weeks. RESULTS:
      The training program increased transforming growth factor-beta1 concentration
      (+50.4%) and reduced high sensitivity C reactive protein levels (-24.1%) without
      altering the levels of interleukin-6, interleukin-10, interferon-gamma and tumor
      necrosis factor-alpha. Additional improvements were also achieved in
      anthropometric characteristics, glycated hemoglobin (HbA1c: -11.8%), homeostasis
      model assessment of insulin resistance index (HOMA-IR: -15%) and physical fitness
      parameters (stress test: +26.6%, upper muscle strength: +32.4% and lower muscle
      strength: +48.9%). CONCLUSION: A combined strength and aerobic exercise program
      has a potential anti-atherogenic and anti-inflammatory impact which most likely
      reduces the risk of cardiovascular disease and improves the health status in
      patients with type 2 diabetes.

PMID- 21724538
TI  - Vitamin D deficiency in white, apparently healthy, free-living adults in a
      temperate region.
AB  - OBJECTIVE: The precise incidence of vitamin D deficiency is not known, primarily
      because there is no consensus on the optimal levels of serum 25(OH)Vitamin D. The
      aim of the present study was to determine the incidence of vitamin D deficiency
      in a large group of normal adult volunteers residing in a typical temperate
      region. DESIGN-METHODS: In 625 healthy, free living adults (553 women, 72 men,
      aged 18-85 years), serum 25(OH)Vitamin D and 1-25(OH)2 Vitamin D (RIA), plasma
      intact PTH (ECLIA) and routine chemistries (multianalyser) were determined at
      baseline once during a whole year. In a subgroup of 36 subjects, a vitamin D
      loading (suppression) test was also performed to define the lower normal values
      for these two Vitamin D metabolites. RESULTS: The estimated lower normal values,
      based on the results of the vitamin D2 loading test, were 22 ng/ml (55 nmol/L)
      for 25(OH)Vitamin D and 24.6 pg/ml (59 pmol/l) for 1-25(OH)2 Vitamin D. During
      the whole year, the incidence of low values was 57.7% for 25(OH)Vitamin D and
      33.2% for 1-25(OH)2 Vitamin D. A highly significant (p<0.001) positive linear
      correlation of serum 25(OH)Vitamin D with 1-25(OH)2 Vitamin D values and a
      negative correlation of 25(OH)Vitamin D with intact PTH was observed in the
      entire group and separately in women without or with osteoporosis and osteopenia.
      CONCLUSION: Most of the white normal adults living in a temperate region were
      vitamin D deficient. The observed correlations between serum concentrations of
      25(OH)Vitamin D and 1-25(OH)2 Vitamin D as well as of 25(OmicronEta)Vitamin D and
      intact PTH, suggest that 25(OH)Vitamin D is implicated not only in 1-25(OH)2
      Vitamin D production but also in PTH secretion.

PMID- 21724539
TI  - Secular trends in growth of African Pygmies and Bantu.
AB  - OBJECTIVE: The aim of this study was to investigate whether a secular trend in
      growth occurred during the last century in Pygmies from Cameroon (West Pygmies)
      and in Bantu rural farmers, the latter being studied to serve as controls.
      DESIGN: The evolution in height of West Pygmies and Bantu farmers from 1911 to
      2006 was evaluated using data from the literature as well as data gathered by our
      research team during an expedition to Cameroon in 2006. RESULTS: During the last
      century, no secular trend in west Pygmies is apparent, as height changed from 151
      cm to 155 cm in males and from 143 cm to 146 cm in females. A small though
      significant (p=0.026), increment (about 2 cm) was observed only in female
      subjects during the last ten years. By contrast, Bantu heights show a significant
      change from 1943 to 2006 for both males (from 159 cm to 172 cm; p=0.025) and
      females (from 148 cm to 160 cm; p=0.029). CONCLUSIONS: Over the last century, the
      Bantu population exhibited a significant secular trend for height, whereas West
      Pygmies did not increase their linear growth. The lack of secular trend in
      Pygmies possibly suggests that their stature reflects adaptation to the forest
      lifestyle. We may hypothesize that not only environmental but epigenetic factors
      have also contributed to their growth potential.

PMID- 21724540
TI  - Monitoring of lipodystrophic and metabolic abnormalities in HIV-1 infected
      children on antiretroviral therapy.
AB  - OBJECTIVE: Few studies have thus far assessed body composition by dual energy X
      ray absorptrometry (DXA) in children with HIV, primarily because reference data
      for normally growing children and adolescents are not available. Our study aimed
      at evaluating body composition in children with HIV and their relatiomicronn to
      serum lipids and glucose homeostasis. DESIGN: Body composition was assessed by
      DXA in 17 HIV-1 infected children at entrance to the study and after 12 months
      and in one hundred fifty nine age, gender, body mass index (BMI), and Tanner
      stage matched healthy subjects who served as controls. Lipodystrophy was
      diagnosed if the trunk/leg fat ratio was out of the range of the expected mean +/
      1SD of the controls. RESULTS: At study entry, 10 patients (7 girls) had
      developed lipohypertrophy, whereas all remaining patients had lipoatrophy.
      Lipohypertrophy was associated with older age (p=0.027). Lipodystrophic phenotype
      was stable in all patients except in one over the 12-month period of follow-up
      while on continuous antiretroviral therapy (ART). 80% and 70% of patients with
      lipohypertrophy had triglycerides and cholesterol levels, respectively above the
      75th percentile, while 57% and 43% of patients with lipoatrophy had triglycerides
      and cholesterol, respectively greater than the 75th percentile. High
      triglycerides were associated with the use of protease inhibitors (p=0.028).
      Basal fasting glucose and homeostasis model assessment (HOMA) values were within
      normal limits. CONCLUSIONS: HIV-infected paediatric patients on continuous ART
      developed significant and persistent body composition changes which were
      associated with dyslipidemia without overt abnormalities of glucose metabolism.

PMID- 21724541
TI  - Insulin-mediated "pseudoacromegaly".
AB  - Patients with acromegaly have characteristic clinical features caused by soft
      tissue overgrowth. The most common cause of acromegaly is a growth hormone
      secreting adenoma of the anterior pituitary. Both somatic and metabolic features
      of acromegaly are due to excess growth hormone (GH) secretion and high serum
      concentrations of insulin-like growth factor-I (IGF-I). Here we present a case of
      "pseudoacromegaly" with an acromegaloid phenotype, insulin resistance, history of
      adenomatous colonic polyp, and suppressed IGF-I levels. Patients with this rare
      condition are likely to have a selective post-receptor defect of insulin
      signalling, leading to the impairment of metabolic but preservation of mitogenic
      signalling. Endocrinologists should consider this diagnosis when assessing
      patients with clinical features of acromegaly and insulin resistance, in the
      absence of elevated levels of GH and IGF-I.

PMID- 21724543
TI  - Global response to non-communicable disease.

PMID- 21724542
TI  - Aggressive silent corticotroph adenoma progressing to pituitary carcinoma: the
      role of temozolomide therapy.
AB  - Temozolomide (TMZ) has recently been recommended as a novel approach in the
      management of aggressive pituitary tumors. Herein, we present the case of a 43
      year-old man with a 20-year history of silent subtype 2 pituitary corticotroph
      adenoma. Nine surgical resections and radiotherapy had failed to provide a cure.
      Morphological evaluation of the tumor revealed a mildly pleomorphic adenoma, the
      cells of which showed low-level cell proliferative activity with Ki67, increased
      topoisomerase II alpha index and conclusive O-6-methylguanine-DNA
      methyltransferase (MGMT) as well as vascular endothelial growth factor (VEGF)
      immunoreactivity. Given its aggressive behavior and failure of conventional
      therapy, TMZ was administered. The treatment was continued even after MGMT
      immunopositivity was identified, but failed to decrease MGMT immunoexpression and
      exerted no morphologic effect. Examination of the lesion after TMZ therapy showed
      neither morphologic nor immunohistochemical alterations. In our case, TMZ
      administration, despite changing the TMZ dosing regimen to prompt a drug
      response, was incapable of depleting MGMT stores.

PMID- 21724544
TI  - Provision of health information for all.

PMID- 21724545
TI  - Clinical data on high risk medical devices should be made publicly available.

PMID- 21724546
TI  - BMA meeting: BMA votes in favour of banning smoking in cars.

PMID- 21724547
TI  - UK public must expect to pay for long term care, says care services minister.

PMID- 21724548
TI  - Changes to NHS reforms will increase bureaucracy and treble the number of
      statutory organisations.

PMID- 21724549
TI  - More than one third of diabetic patients have poor blood glucose control, shows
      audit.

PMID- 21724550
TI  - BMA meeting: BMA will ballot on industrial action if government imposes pension
      changes.

PMID- 21724551
TI  - In vitro and in vivo selective antitumor activity of a novel orally bioavailable
      proteasome inhibitor MLN9708 against multiple myeloma cells.
AB  - PURPOSE: The success of bortezomib therapy for treatment of multiple myeloma (MM)
      led to the development of structurally and pharmacologically distinct novel
      proteasome inhibitors. In the present study, we evaluated the efficacy of one
      such novel orally bioactive proteasome inhibitor MLN9708/MLN2238 in MM using well
      established in vitro and in vivo models. EXPERIMENTAL DESIGN: MM cell lines,
      primary patient cells, and the human MM xenograft animal model were used to study
      the antitumor activity of MN2238. RESULTS: Treatment of MM cells with MLN2238
      predominantly inhibits chymotrypsin-like activity of the proteasome and induces
      accumulation of ubiquitinated proteins. MLN2238 inhibits growth and induces
      apoptosis in MM cells resistant to conventional and bortezomib therapies without
      affecting the viability of normal cells. In animal tumor model studies, MLN2238
      is well tolerated and inhibits tumor growth with significantly reduced tumor
      recurrence. A head-to-head analysis of MLN2238 versus bortezomib showed a
      significantly longer survival time in mice treated with MLN2238 than mice
      receiving bortezomib. Immununostaining of MM tumors from MLN2238-treated mice
      showed growth inhibition, apoptosis, and a decrease in associated angiogenesis.
      Mechanistic studies showed that MLN2238-triggered apoptosis is associated with
      activation of caspase-3, caspase-8, and caspase-9; increase in p53, p21, NOXA,
      PUMA, and E2F; induction of endoplasmic reticulum (ER) stress response proteins
      Bip, phospho-eIF2-alpha, and CHOP; and inhibition of nuclear factor kappa B.
      Finally, combining MLN2238 with lenalidomide, histone deacetylase inhibitor
      suberoylanilide hydroxamic acid, or dexamethasone triggers synergistic anti-MM
      activity. CONCLUSION: Our preclinical study supports clinical evaluation of
      MLN9708, alone or in combination, as a potential MM therapy.

PMID- 21724552
TI  - Aging, COPD, and other risk factors do not explain the increased prevalence of
      pulmonary Mycobacterium avium complex in Ontario.
AB  - BACKGROUND: The cause of observed increases in pulmonary Mycobacterium avium
      complex (pMAC) isolation and disease is unexplained. To explore possible causes
      of the increase in pMAC isolation and disease prevalence in Ontario, Canada, we
      studied age and other population-level risk factors. METHODS: We determined age
      and sex of patients with pMAC disease between 2003 and 2008. We then estimated
      whether the potential effect of population aging and changes in prevalence of HIV
      infection, solid organ transplant, COPD, and tumor necrosis factor-alpha (TNF
      alpha) inhibition have contributed to the observed increase in pMAC disease.
      RESULTS: During 2003 to 2008, pMAC isolation and disease prevalence (per 100,000)
      both increased (8.44 to 12.62 and 4.35 to 6.81, respectively). The total number
      of cases of disease increased by 348 (2.46 per 100,000). Based on actual
      contemporary population changes, aging could explain 70 additional cases
      (increase of 0.57 per 100,000). The increase in self-reported COPD prevalence
      could potentially explain 11 (95% CI, 0-42) additional cases (increase of 0.09
      per 100,000 [95% CI, 0-0.34 per 100,000]). HIV infection, solid organ transplant,
      and TNF-alpha inhibition combined could potentially explain no more than 73
      additional cases (increase of 0.60 per 100,000). CONCLUSIONS: Although population
      aging appears to be a major risk factor, the increase in pMAC disease in Ontario
      could be only partly explained by aging, increases in COPD, HIV, solid organ
      transplantation, and TNF-alpha inhibition therapy. The increase in pMAC is likely
      multifactorial and may be affected by environmental or pathogen factors not
      addressed in this study.

PMID- 21724553
TI  - Double-stranded RNA is pathogenic in Drosophila models of expanded repeat
      neurodegenerative diseases.
AB  - The pathogenic agent responsible for the expanded repeat diseases, a group of
      neurodegenerative diseases that includes Huntington's disease is not yet fully
      understood. Expanded polyglutamine (polyQ) is thought to be the toxic agent in
      certain cases, however, not all expanded repeat disease genes can encode a polyQ
      sequence. Since a repeat-containing RNA intermediary is common to all of these
      diseases, hairpin-forming single-stranded RNA has been investigated as a
      potential common pathogenic agent. More recently, it has become apparent that
      most of the expanded repeat disease loci have transcription occurring from both
      strands, raising the possibility that the complementary repeat RNAs could form a
      double-stranded structure. In our investigation using Drosophila models of these
      diseases, we identified a fortuitous integration event that models bidirectional
      repeat RNA transcription with the resultant flies exhibiting inducible pathology.
      We therefore established further lines of Drosophila expressing independent
      complementary repeat RNAs and found that these are toxic. The Dicer pathway is
      essential for this toxicity and in neuronal cells accounts for metabolism of the
      high copy number (CAG.CUG)(100) double-stranded RNAs down to (CAG)(7) single
      stranded small RNAs. We also observe significant changes to the microRNA profile
      in neurons. These data identify a novel pathway through which double-stranded
      repeat RNA is toxic and capable of eliciting symptoms common to neurodegenerative
      human diseases resulting from dominantly inherited expanded repeats.

PMID- 21724554
TI  - High prevalence of laminopathies among patients with metabolic syndrome.
AB  - Constitutional laminopathies, such as the Dunnigan familial partial
      lipodystrophy, are severe diseases caused by mutations in A-type lamins and share
      several features with metabolic syndrome (MS). In this study, we hypothesized
      that MS may be, in some cases, a mild form of laminopathies and use the abnormal
      cell nucleus phenotype observed in these diseases as a primary screening test in
      patients suffering from common MS. Nuclear shape and lamin A nucleoplasmic
      distribution abnormalities were systematically searched in lymphoblastoid cells
      of 87 consecutive patients with MS. In parallel, five genes encoding either the A
      type lamins or the enzymes of the lamin A maturation pathway were systematically
      sequenced (LMNA, ZMPSTE24, ICMT, FNTA and FNTB). We identified 10 MS patients
      presenting abnormal nuclear shape and disturbed lamin A/C nuclear distribution.
      These patients were not clinically different from those without nuclear
      abnormalities except that they were younger, and had higher triglyceridemia and
      SGPT levels. Three of them carry a heterozygous mutation in LMNA or in ZMPSTE24,
      a gene encoding one of the lamin A processing enzymes. All three mutations are
      novel missense mutations predicted to be damaging. Both lymphoblastoid cells and
      skin fibroblasts from the patient carrying the mutation in ZMPSTE24, showed
      accumulation of lamin A precursor, indicating an alteration of the lamin A
      processing, confirmed by functional study. Together, these results show for the
      first time, that a significant proportion of MS patients exhibits laminopathies
      and suggest that systematic investigation of lamin A and its partners should be
      performed at the diagnosis of this syndrome.

PMID- 21724555
TI  - Royal College of Surgeons failed to follow up its critical report on Mid
      Staffordshire trust, inquiry hears.

PMID- 21724557
TI  - US needs new strategy to help 116 million patients in chronic pain.

PMID- 21724556
TI  - EU drive to free movement of doctors across Europe could damage patient safety,
      warns GMC.

PMID- 21724558
TI  - Doctor who spiked girlfriend's drink to induce abortion is struck off.

PMID- 21724559
TI  - MPs lambast government for haste in closing down Forensic Science Service.

PMID- 21724561
TI  - Development of 50 malaria drugs is under threat unless funding expands.

PMID- 21724560
TI  - Association of echocardiography before major elective non-cardiac surgery with
      postoperative survival and length of hospital stay: population based cohort
      study.
AB  - OBJECTIVE: To determine the association of resting echocardiography before
      elective intermediate to high risk non-cardiac surgery with survival and length
      of hospital stay. DESIGN: Population based retrospective cohort study. SETTING:
      Acute care hospitals in Ontario, Canada, between 1 April 1999 and 31 March 2008.
      PARTICIPANTS: Patients aged over 40 years who had elective intermediate to high
      risk non-cardiac surgery. INTERVENTION: Resting echocardiography within 6 months
      before surgery. MAIN OUTCOME MEASURES: Postoperative survival (30 days and 1
      year) and length of hospital stay; postoperative surgical site infection as an
      outcome for which no association with echocardiography would be expected.
      RESULTS: Of the 264,823 patients in the entire cohort, 15.1% (n = 40,084) had
      echocardiography. After use of propensity score methods to assemble a matched
      cohort (n = 70,996) that reduced differences between patients who had or had not
      had echocardiography, echocardiography was associated with increases in 30 day
      mortality (relative risk 1.14, 95% confidence interval 1.02 to 1.27), 1 year
      mortality (1.07, 1.01 to 1.12), and length of hospital stay but no difference in
      surgical site infections (1.03, 0.98 to 1.06). The association with mortality was
      influenced (P = 0.02) by whether patients had had stress testing or had risk
      factors for cardiac complications. No association existed between
      echocardiography and mortality among patients who had stress testing (relative
      risk 1.01, 0.92 to 1.11) or among patients at high risk who had not had stress
      testing (1.00, 0.87 to 1.13). However, echocardiography was associated with
      mortality in patients at low risk (relative risk 1.44, 1.14 to 1.82) and
      intermediate risk (1.10, 1.02 to 1.18) who had not had stress testing.
      CONCLUSIONS: Preoperative echocardiography was not associated with improved
      survival or shorter hospital stay after major non-cardiac surgery. These findings
      highlight the need for further research to guide better use of this common
      preoperative test.

PMID- 21724562
TI  - BMA meeting: BMA condemns government's "responsibility deals" with food and
      drinks industry.

PMID- 21724563
TI  - Destined to die.

PMID- 21724564
TI  - Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo
      controlled trial (CRASH-2 Intracranial Bleeding Study).
AB  - OBJECTIVE: To assess the effect of tranexamic acid (which reduces bleeding in
      surgical patients and reduces mortality due to bleeding in trauma patients) on
      intracranial haemorrhage in patients with traumatic brain injury. METHODS: A
      nested, randomised, placebo controlled trial. All investigators were masked to
      treatment allocation. All analyses were by intention to treat. Patients 270 adult
      trauma patients with, or at risk of, significant extracranial bleeding within 8
      hours of injury, who also had traumatic brain injury. INTERVENTIONS: Patients
      randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then
      infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES:
      Intracranial haemorrhage growth (measured by computed tomography) between
      hospital admission and then 24-48 hours later, with adjustment for Glasgow coma
      score, age, time from injury to the scans, and initial haemorrhage volume.
      RESULTS: Of the 133 patients allocated to tranexamic acid and 137 allocated to
      placebo, 123 (92%) and 126 (92%) respectively provided information on the primary
      outcome. All patients provided information on clinical outcomes. The mean total
      haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic
      acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence
      interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%)
      patients in the tranexamic acid group versus 12 (9%) in the placebo group
      (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14
      (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group
      (adjusted odds ratio 0.47 (0.21 to 1.04)). CONCLUSIONS: This trial shows that
      neither moderate benefits nor moderate harmful effects of tranexamic acid in
      patients with traumatic brain injury can be excluded. However, the analysis
      provides grounds for further clinical trials evaluating the effect of tranexamic
      acid in this population. Trial registration ISRCTN86750102.

PMID- 21724565
TI  - Tranexamic acid for traumatic brain injury.

PMID- 21724566
TI  - BMA meeting: Doctors back BMA's refusal to join debate on assisted dying.

PMID- 21724567
TI  - Binocular and monocular depth cues in online feedback control of 3D pointing
      movement.
AB  - Previous work has shown that humans continuously use visual feedback of the hand
      to control goal-directed movements online. In most studies, visual error signals
      were predominantly in the image plane and, thus, were available in an observer's
      retinal image. We investigate how humans use visual feedback about finger depth
      provided by binocular and monocular depth cues to control pointing movements.
      When binocularly viewing a scene in which the hand movement was made in free
      space, subjects were about 60 ms slower in responding to perturbations in depth
      than in the image plane. When monocularly viewing a scene designed to maximize
      the available monocular cues to finger depth (motion, changing size, and cast
      shadows), subjects showed no response to perturbations in depth. Thus, binocular
      cues from the finger are critical to effective online control of hand movements
      in depth. An optimal feedback controller that takes into account the low
      peripheral stereoacuity and inherent ambiguity in cast shadows can explain the
      difference in response time in the binocular conditions and lack of response in
      monocular conditions.

PMID- 21724568
TI  - The 'incessant menstruation' hypothesis: a mechanistic ovarian cancer model with
      implications for prevention.
AB  - Serous, endometrioid, clear cell and mucinous histotypes are the most common
      epithelial ovarian cancer. Most serous cancers appear to originate from precursor
      lesions at the fimbriated tubal end, whereas most endometrioid and clear cell
      cancers seem to derive from atypical endometriosis. Data regarding hormonal
      factors and associated gynaecologic conditions were critically analysed with the
      objective of defining a carcinogenic model for sporadic epithelial ovarian cancer
      complying with epidemiologic and pathologic findings. Oral contraceptives and
      tubal ligation substantially reduce the risk of serous, endometrioid and clear
      cell subgroups, but have no significant effect on mucinous tumours, which
      probably follow a different oncogenic pathway. We hypothesize that serous,
      endometrioid and clear cell cancers share a common pathogenic mechanism, i.e.
      iron-induced oxidative stress derived from retrograde menstruation. Fimbriae
      floating in bloody peritoneal fluid are exposed to the action of catalytic iron
      and to the genotoxic effect of reactive oxygen species, generated from haemolysis
      of erythrocytes by pelvic macrophages. This would explain the distal site of
      tubal intraepithelial neoplasia. Collection of blood inside endometriomas would
      lead to the same type of genotoxic insult on gonadal endometrial implants. This
      would explain why endometriosis-associated cancers develop much more frequently
      in the ovary than at extragonadal sites. In women not seeking conception,
      bilateral salpingectomy could be advised whenever planning surgery for
      independent indications, thus possibly reducing cancer risk, while preserving
      ovarian function. The use of oral contraceptives should be favoured for prolonged
      periods of time, especially in women with endometriosis, a population at doubled
      risk of gonadal malignancy.

PMID- 21724570
TI  - Childhood outcomes of assisted reproductive technology.
AB  - There is a large population of children conceived via assisted reproductive
      technology (ART), which continues to increase worldwide, without a clear
      understanding of associated long-term outcomes. ART children are more likely to
      be the result of multiple pregnancies, and thus to be born prematurely or low
      birthweight. There is growing evidence that ART children are phenotypically and
      biochemically different from naturally conceived children, but the mechanism(s)
      leading to these changes have not been elucidated. There is a possible increased
      risk of rare imprinted gene disorders in these children. However, it remains
      unclear whether more subtle changes in DNA methylation occur commonly, leading to
      differences in gene expression and phenotype in ART children. Although an
      increased risk of cancer among ART children has been reported, the role of ART in
      the development of cancer has not been demonstrated. Further research and ongoing
      surveillance of ART children is essential to better understand the possible
      effects of ART on the long-term health of this population.

PMID- 21724569
TI  - Sustained fertility from 22 to 41 years of age in women with polycystic ovarian
      syndrome.
AB  - BACKGROUND: Subfertility due to chronic anovulation is common in women with
      polycystic ovary syndrome (PCOS) and is often treated with IVF. Women with PCOS
      have an increased ovarian follicle and oocyte count, increased ovarian reserve
      and/or a slower rate of follicle atresia. If so, one would expect women with PCOS
      to display a delayed reduction in fertility with advancing age as compared with
      eumenorrheic women. METHODS: To test this hypothesis, we compared oocyte count
      and live birth rates among two groups undergoing IVF, 500 women with PCOS and 500
      eumenorrheic women with infertility due to tubal factor only. RESULTS: Across the
      age range of 22-41 years, oocyte count and live birth rates remained stable in
      women with PCOS. In the eumenorrheic comparison group, these parameters decreased
      significantly with age. CONCLUSIONS: Women with PCOS display sustained fertility
      with advancing age as compared with infertile eumenorrheic women.

PMID- 21724571
TI  - The functions of the nervus intermedius.

PMID- 21724572
TI  - Acute hepatic (or hyperammonemic) encephalopathy: diffuse cortical injury and the
      significance of ammonia.

PMID- 21724573
TI  - Clinical correlates of white matter blood flow perfusion changes in Sturge-Weber
      syndrome: a dynamic MR perfusion-weighted imaging study.
AB  - BACKGROUND AND PURPOSE: Low brain tissue perfusion due to abnormal venous
      drainage is thought to be a central mechanism of brain damage in SWS. Here, HR
      PWI was used to quantify WM perfusion abnormalities and to correlate these with
      brain atrophy and clinical variables. MATERIALS AND METHODS: Fourteen children
      (age range, 0.8-10.0 years) with unilateral SWS underwent MR imaging
      examinations, including HR-PWI. rCBV, rCBF, and MTT in the affected WM and in
      contralateral homotopic WM were measured. AI for each perfusion parameter was
      correlated with age, brain atrophy, and motor and seizure variables as well as
      IQ. RESULTS: Increased perfusion was seen in the affected hemisphere in 5
      children and decreased perfusion in 9 children. Brain atrophy was more severe in
      the low-perfusion group (P = .01) and was related to both CBF-AI and CBV-AI (r = 
      0.69, P = .007; r = -0.64, P = .014, respectively). Older children had lower CBV
      values on the affected side (r = -0.62, P = .02). Longer duration of epilepsy was
      related to lower CBF (more negative CBF-AI, r = -0.58, P = .03) and low CBV (r = 
      0.55, P = .04) on the affected side. Lower perfusion was associated with more
      frequent seizures (rCBF-AI: r = -0.56, P = .04; rCBV-AI: r = -0.63, P = .02).
      CONCLUSIONS: Increased perfusion in the affected cerebral WM may indicate an
      early stage of SWS without severe brain atrophy. Decreased perfusion is
      associated with frequent seizures, long duration of epilepsy, and brain atrophy.

PMID- 21724574
TI  - MR imaging of parotid tumors: typical lesion characteristics in MR imaging
      improve discrimination between benign and malignant disease.
AB  - BACKGROUND AND PURPOSE: The surgical approach to parotid tumors is different for
      benign and malignant neoplasms, but the clinical symptoms do not correlate well
      with histology. Difficulties in tumor classification also arise in imaging
      modalities, in which sonography has the lowest and MR imaging, the highest
      accuracy. The purpose of this study was to review our experience using
      conventional MR imaging of the neck in the evaluation of parotid tumors and to
      evaluate which MR imaging findings are best able to predict malignant histology.
      MATERIALS AND METHODS: Eighty-four consecutive patients (43 males, 41 females;
      median age, 56 years; range, 9-85 years) with parotid gland tumors who underwent
      MR imaging before surgery were prospectively included in the present study and
      retrospectively analyzed. Histology was available for all tumors. We analyzed the
      following MR imaging parameters: signal intensity, contrast enhancement, lesion
      margins (well-defined versus ill-defined), lesion location (deep/superficial
      lobe), growth pattern (focal, multifocal, or diffuse), and extension into
      neighboring structures, perineural spread, and lymphadenopathy. RESULTS: The 57
      (68%) benign and 27 (32%) malignant tumors consisted of 29 pleomorphic adenomas,
      17 Warthin tumors, 11 various benign tumors, 5 mucoepidermoid carcinomas, 3
      adenoid cystic carcinomas, 1 acinic cell carcinoma, 1 carcinoma ex pleomorphic
      adenoma, 9 metastases, and 8 various malignant neoplasms. Specific signs
      predictive of malignancy were the following: T2 hypointensity of the parotid
      tumor (P = .048), ill-defined margins (P = .001), diffuse growth (P = .012),
      infiltration of subcutaneous tissue (P = .0034), and lymphadenopathy (P = .012).
      CONCLUSIONS: Low signal intensity on T2-weighted images and postcontrast ill
      defined margins of a parotid tumor are highly suggestive of malignancy.

PMID- 21724575
TI  - Risks of colon and rectal adenomas are differentially associated with
      anthropometry throughout life: the French E3N prospective cohort.
AB  - BACKGROUND: Associations between adult anthropometry and risk of colorectal
      neoplasms are well established. However, whereas body mass in infancy and
      childhood has been associated with risk of some cancers, little is known about
      potential associations with colorectal neoplasms. The authors investigated
      associations between colorectal adenoma risk and lifetime anthropometry, in an
      attempt to better understand the relationships between anthropometric features
      and colorectal carcinogenesis. METHODS: Among the 17 391 women of the French E3N
      cohort who underwent a colonoscopy during follow-up (1993-2002), 1408 developed a
      first colorectal adenoma. Associations were estimated with Cox multivariate
      proportional hazard regression models. RESULTS: Left colon adenoma risk was
      associated with high birth weight [hazard ratio (HR) high vs median = 1.21; 95%
      confidence interval (95% CI): 1.00-1.47, P(trend) = 0.03] and large adult body
      shape (HR = 1.28; 95% CI: 1.04-1.56, P(trend) = 0.02). A large versus small body
      shape at age 8 years and at menarche were associated with a decreased rectal
      adenoma risk [HR = 0.68; 95% CI: 0.49-0.95, P(trend) = 0.01 and 0.73 (0.53-1.01),
      P(trend) = 0.05, respectively]. Except for a positive association with large vs
      median birth weight, no anthropometric characteristic was associated with right
      colon adenoma risk. Associations did not differ between advanced and non-advanced
      adenomas. CONCLUSIONS: These findings suggest that early life events may
      influence early stages of colorectal carcinogenesis and add to the evidence of
      differential pathways of carcinogenesis in the right colon, left colon and
      rectum.

PMID- 21724577
TI  - Commentary: Measuring nutritional status of children.

PMID- 21724576
TI  - The effect of water and sanitation on child health: evidence from the demographic
      and health surveys 1986-2007.
AB  - BACKGROUND: Despite continued national and international efforts, access to
      improved water and sanitation remains limited in many developing countries. The
      health consequences of lacking access to water and sanitation are severe, and
      particularly important for child development. METHODS: To investigate the
      associations between child health and access to water and sanitation, we merged
      all available Demographic and Health Surveys (DHS) with complete birth histories
      and water and sanitation information. The merged data set of 171 surveys includes
      information on 1.1 million children under the age of 5 years in 70 low- and
      middle-income countries over the period 1986-2007. We used logistic models to
      estimate the effect of water and sanitation access on infant and child mortality,
      diarrhoea and stunting. RESULTS: Access to improved sanitation was associated
      with lower mortality (OR = 0.77, 95% CI 0.68-0.86), a lower risk of child
      diarorhea (OR = 0.87, 95% CI 0.85-0.90) and a lower risk of mild or severe
      stunting (OR = 0.73, 95% CI 0.71-0.75). Access to improved water was associated
      with a lower risk of diarrhoea (OR = 0.91, 95% CI 0.88-0.94) and a lower risk of
      mild or severe stunting (OR = 0.92, 95% CI 0.89-0.94), but did not show any
      association with non-infant child mortality (OR = 0.97, 95% CI 0.88-1.04).
      CONCLUSIONS: Although our point estimates indicate somewhat smaller protective
      effects than some of the estimates reported in the existing literature, the
      results presented in this article strongly underline the large health
      consequences of lacking access to water and sanitation for children aged <5 years
      in low- and middle-income countries.

PMID- 21724578
TI  - South Asians have adverse cerebrovascular haemodynamics, despite equivalent blood
      pressure, compared with Europeans. This is due to their greater hyperglycaemia.
AB  - BACKGROUND: South Asians have a 1.5-fold increased stroke mortality compared with
      Europeans, despite similar blood pressures (BP). We hypothesized that it is the
      greater hyperglycaemia in South Asians that increases stroke risk, by adversely
      affecting cerebrovascular haemodynamics. METHODS: A population-based sample of
      149 Europeans and 151 South Asians underwent metabolic profiling and concurrent
      measurement of finger BP using a Finapres and middle cerebral artery (MCA) blood
      flow velocity using transcranial Doppler ultrasound. Cerebrovascular
      autoregulation, cerebrovascular resistance [resistive index (RI) and pulsatility
      index (PI)] were calculated. Means of cerebrovascular haemodynamic measures were
      compared by ethnicity, with the introduction of explanatory variables to a
      regression model to determine which variable could best account for ethnic
      differences. RESULTS: Cerebrovascular resistance (RI) was 12.9 * 10(3) (0.9-24.8,
      P = 0.04) greater in South Asians than Europeans. Systolic, diastolic and mean
      MCA velocities were also higher in South Asians (mean velocity 41.4 +/- 8.0 cm/s
      vs 38.0 +/- 8.0 cm/s, respectively, P = 0.001). Low frequency gain, a measure of
      autoregulation, was worse in South Asians compared with Europeans (0.50 +/- 0.01
      cm/s mm/Hg vs 0.45 +/- 0.01 cm/s mm/Hg, P = 0.01). RI positively correlated with
      HbA(1c) (r = 0.184; P < 0.01). Adjustment for BP could not explain the higher RI
      in South Asians, but adjustment for HbA(1c) abolished the ethnic difference in RI
      (5.8 * 10(3) (-6.5 to 18.1, P = 0.4). CONCLUSIONS: Cerebrovascular resistance and
      autoregulation are worse in South Asians than in Europeans, despite equivalent
      resting BP. The greater hyperglycaemia in South Asians accounts for their adverse
      cerebrovascular resistance. This could explain excess stroke in South Asians but
      requires testing in longitudinal studies.

PMID- 21724579
TI  - Oncogenic events associated with endometrial and ovarian cancers are rare in
      endometriosis.
AB  - Endometriosis displays some features that resemble malignant processes, including
      invasive growth, resistance to apoptosis and distant implantation. The objective
      of this study was to investigate whether gene alterations that are frequent in
      endometrial and/or ovarian cancers contribute to the pathogenesis of
      endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23
      patients with revised American Fertility Score stage 1 (n= 1), 2 (n= 10), 3 (n=
      11) or 4 (n= 1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1 and
      ESR1) were analyzed for promoter hypermethylation using methylation-specific
      melting curve analysis, and 9 genes (BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3,
      PIK3CA, TP53 and PTEN) were analyzed for mutations using denaturing gradient gel
      electrophoresis and direct sequencing. An oncogenic mutation in KRAS (c.34G > T;
      p.G12C) was detected in a single lesion. No gene alterations were found in the
      remaining samples. Our data suggest that genetic and epigenetic events
      contributing to endometrial and ovarian cancers are rare in endometriosis.
      However, other proto-oncogenes and tumor suppressor genes should be tested for
      alterations in order to identify the molecular basis of the susceptibility of
      endometriosis to malignant transformation.

PMID- 21724580
TI  - Effects of supplemental vitamin D and calcium on biomarkers of inflammation in
      colorectal adenoma patients: a randomized, controlled clinical trial.
AB  - Vitamin D and calcium affect several pathways involved in inflammation, tumor
      growth, and immune surveillance relevant to carcinogenesis. Also, epidemiologic
      evidence indicates that calcium and vitamin D may reduce risk for developing
      colorectal adenomas and cancer. To investigate the effects of calcium and vitamin
      D on biomarkers of inflammation in colorectal adenoma patients, we conducted a
      pilot, randomized, double-blind, placebo-controlled, 2 * 2 factorial clinical
      trial (n = 92) of 2 g/d calcium and/or 800 IU/d vitamin D(3) supplementation
      versus placebo over 6 months. Plasma concentrations of proinflammatory markers [C
      reactive protein (CRP), TNF-alpha, interleukin (IL)-6, IL-1beta, and IL-8] and an
      anti-inflammatory marker (IL-10) were measured using ELISAs. After 6 months of
      treatment, in the vitamin D(3) supplementation group, CRP decreased 32% overall
      (P = 0.11), 37% in men (P = 0.05), and 41% among non-nonsteroidal anti
      inflammatory drug (NSAID) users (P = 0.05) relative to placebo. In the vitamin
      D(3) supplementation group, TNF-alpha decreased 13%, IL-6 32%, IL-1beta 50%, and
      IL-8 15%; in the calcium supplementation group, IL-6 decreased 37%, IL-8 11%, and
      IL-1beta 27%. Although these changes were not statistically significant, a
      combined inflammatory markers z-score decreased 77% (P = 0.003) in the vitamin
      D(3) treatment group overall, 83% (P = 0.01) among men, and 48% among non-NSAID
      users (P = 0.01). There was no evidence of synergy between vitamin D(3) and
      calcium or effects on IL-10. These preliminary results are consistent with a
      pattern of reduction in tumor-promoting inflammation biomarkers with vitamin D(3)
      or calcium supplementation alone and support further investigation of vitamin
      D(3) as a chemopreventive agent against inflammation and colorectal neoplasms.

PMID- 21724582
TI  - You say resistance, I say compliance; let's call the whole thing cerebral
      Windkessel control.

PMID- 21724583
TI  - Beyond the target area: remote effects of non-invasive brain stimulation in
      humans.

PMID- 21724584
TI  - Paired comparison of water, energy and carbon exchanges over two young maritime
      pine stands (Pinus pinaster Ait.): effects of thinning and weeding in the early
      stage of tree growth.
AB  - The effects of management practices on energy, water and carbon exchanges were
      investigated in a young pine plantation in south-west France. In 2009-10, carbon
      dioxide (CO(2)), H(2)O and heat fluxes were monitored using the eddy covariance
      and sap flow techniques in a control plot (C) with a developed gorse layer, and
      an adjacent plot that was mechanically weeded and thinned (W). Despite large
      differences in the total leaf area index and canopy structure, the annual net
      radiation absorbed was only 4% lower in plot W. We showed that higher albedo in
      this plot was offset by lower emitted long-wave radiation. Annual
      evapotranspiration (ET) from plot W was 15% lower, due to lower rainfall
      interception and transpiration by the tree canopy, partly counterbalanced by the
      larger evaporation from both soil and regrowing weedy vegetation. The drainage
      belowground from plot W was larger by 113 mm annually. The seasonal variability
      of ET was driven by the dynamics of the soil and weed layers, which was more
      severely affected by drought in plot C. Conversely, the temporal changes in pine
      transpiration and stem diameter growth were synchronous between sites despite
      higher soil water content in the weeded plot. At the annual scale, both plots
      were carbon sinks, but thinning and weeding reduced the carbon uptake by 73%:
      annual carbon uptake was 243 and 65 g C m(-2) on plots C and W, respectively.
      Summer drought dramatically impacted the net ecosystem exchange: plot C became a
      carbon source as the gross primary production (GPP) severely decreased. However,
      plot W remained a carbon sink during drought, as a result of decreases in both
      GPP and ecosystem respiration (R(E)). In winter, both plots were carbon sources,
      plots C and W emitting 67.5 and 32.4 g C m(-2), respectively. Overall, this study
      highlighted the significant contribution of the gorse layer to mass and energy
      exchange in young pine plantations.

PMID- 21724585
TI  - Hydraulic patterns and safety margins, from stem to stomata, in three eastern
      U.S. tree species.
AB  - Adequate water transport is necessary to prevent stomatal closure and allow for
      photosynthesis. Dysfunction in the water transport pathway can result in stomatal
      closure, and can be deleterious to overall plant health and survival. Although
      much is known about small branch hydraulics, little is known about the
      coordination of leaf and stem hydraulic function. Additionally, the daily
      variations in leaf hydraulic conductance (K(leaf)), stomatal conductance and
      water potential (Psi(L)) have only been measured for a few species. The objective
      of the current study was to characterize stem and leaf vulnerability to hydraulic
      dysfunction for three eastern U.S. tree species (Acer rubrum, Liriodendron
      tulipifera and Pinus virginiana) and to measure in situ daily patterns of
      K(leaf), leaf and stem Psi, and stomatal conductance in the field. Sap flow
      measurements were made on two of the three species to compare patterns of whole
      plant water use with changes in K(leaf) and stomatal conductance. Overall, stems
      were more resistant to hydraulic dysfunction than leaves. Stem P50 (Psi resulting
      in 50% loss in conductivity) ranged from -3.0 to -4.2 MPa, whereas leaf P50
      ranged from -0.8 to -1.7 MPa. Field Psi(L) declined over the course of the day,
      but only P. virginiana experienced reductions in K(leaf) (nearly 100% loss).
      Stomatal conductance was greatest overall in P. virginiana, but peaked midmorning
      and then declined in all three species. Midday stem Psi in all three species
      remained well above the threshold for embolism formation. The daily course of sap
      flux in P. virginiana was bell-shaped, whereas in A. rubrum sap flux peaked early
      in the morning and then declined over the remainder of the day. An analysis of
      our data and data for 39 other species suggest that there may be at least three
      distinct trajectories of relationships between maximum K(leaf) and the % K(leaf)
      at Psi(min). In one group of species, a trade-off between maximum K(leaf) and %
      K(leaf) at Psi(min) appeared to exist, but no trade-off was evident in the other
      two trajectories.

PMID- 21724586
TI  - Overexpression of MBD2 in glioblastoma maintains epigenetic silencing and
      inhibits the antiangiogenic function of the tumor suppressor gene BAI1.
AB  - Brain angiogenesis inhibitor 1 (BAI1) is a putative G protein-coupled receptor
      with potent antiangiogenic and antitumorigenic properties that is mutated in
      certain cancers. BAI1 is expressed in normal human brain, but it is frequently
      silenced in glioblastoma multiforme. In this study, we show that this silencing
      event is regulated by overexpression of methyl-CpG-binding domain protein 2
      (MBD2), a key mediator of epigenetic gene regulation, which binds to the
      hypermethylated BAI1 gene promoter. In glioma cells, treatment with the DNA
      demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dC) was sufficient to
      reactivate BAI1 expression. Chromatin immunoprecipitation showed that MBD2 was
      enriched at the promoter of silenced BAI1 in glioma cells and that MBD2 binding
      was released by 5-Aza-dC treatment. RNA interference-mediated knockdown of MBD2
      expression led to reactivation of BAI1 gene expression and restoration of BAI1
      functional activity, as indicated by increased antiangiogenic activity in vitro
      and in vivo. Taken together, our results suggest that MBD2 overexpression during
      gliomagenesis may drive tumor growth by suppressing the antiangiogenic activity
      of a key tumor suppressor. These findings have therapeutic implications because
      inhibiting MBD2 could offer a strategy to reactivate BAI1 and suppress glioma
      pathobiology.

PMID- 21724587
TI  - Increased VEGFR-2 gene copy is associated with chemoresistance and shorter
      survival in patients with non-small-cell lung carcinoma who receive adjuvant
      chemotherapy.
AB  - VEGF receptor-2 (VEGFR-2 or kinase insert domain receptor; KDR) is a known
      endothelial target also expressed in NSCLC tumor cells. We investigated the
      association between alterations in the KDR gene and clinical outcome in patients
      with resected non-small-cell lung carcinoma (NSCLC; n = 248). KDR copy number
      gains (CNG), measured by quantitative PCR and fluorescence in situ hybridization,
      were detected in 32% of tumors and associated with significantly higher KDR
      protein and higher microvessel density than tumors without CNGs. KDR CNGs were
      also associated with significantly increased risk of death (HR = 5.16; P = 0.003)
      in patients receiving adjuvant platinum-based chemotherapy, but no differences
      were observed in patients not receiving adjuvant therapy. To investigate
      potential mechanisms for these associations, we assessed NSCLC cell lines and
      found that KDR CNGs were significantly associated with in vitro resistance to
      platinum chemotherapy as well as increased levels of nuclear hypoxia inducible
      factor-1alpha (HIF-1alpha) in both NSCLC tumor specimens and cell lines.
      Furthermore, KDR knockdown experiments using small interfering RNA reduced
      platinum resistance, cell migration, and HIF-1alpha levels in cells bearing KDR
      CNGs, providing evidence for direct involvement of KDR. No KDR mutations were
      detected in exons 7, 11, and 21 by PCR-based sequencing; however, two variant
      single nucleotide polymorphism genotypes were associated with favorable overall
      survival in adenocarcinoma patients. Our findings suggest that tumor cell KDR
      CNGs may promote a more malignant phenotype including increased chemoresistance,
      angiogenesis, and HIF-1alpha levels, and that KDR CNGs may be a useful biomarker
      for identifying patients at high risk for recurrence after adjuvant therapy, a
      group that may benefit from VEGFR-2 blockade.

PMID- 21724589
TI  - IL-18 induces PD-1-dependent immunosuppression in cancer.
AB  - Immunosuppressive cytokines subvert innate and adaptive immune responses during
      cancer progression. The inflammatory cytokine interleukin-18 (IL-18) is known to
      accumulate in cancer patients, but its pathophysiological role remains unclear.
      In this study, we show that low levels of circulating IL-18, either exogenous or
      tumor derived, act to suppress the NK cell arm of tumor immunosurveillance. IL-18
      produced by tumor cells promotes the development of NK-controlled metastases in a
      PD-1-dependent manner. Accordingly, PD-1 is expressed by activated mature NK
      cells in lymphoid organs of tumor bearers and is upregulated by IL-18. RNAi
      mediated knockdown of IL-18 in tumors, or its systemic depletion by IL-18-binding
      protein, are sufficient to stimulate NK cell-dependent immunosurveillance in
      various tumor models. Together, these results define IL-18 as an
      immunosuppressive cytokine in cancer. Our findings suggest novel clinical
      implementations of anti-PD-1 antibodies in human malignancies that produce IL-18.

PMID- 21724588
TI  - GPR56 Regulates VEGF production and angiogenesis during melanoma progression.
AB  - Angiogenesis is a critical step during cancer progression. The VEGF is a major
      stimulator for angiogenesis and is predominantly contributed by cancer cells in
      tumors. Inhibition of the VEGF signaling pathway has shown promising therapeutic
      benefits for cancer patients, but adaptive tumor responses are often observed,
      indicating the need for further understanding of VEGF regulation. We report that
      a novel G protein-coupled receptor, GPR56, inhibits VEGF production from the
      melanoma cell lines and impedes melanoma angiogenesis and growth, through the
      serine threonine proline-rich segment in its N-terminus and a signaling pathway
      involving protein kinase Calpha. We also present evidence that the two fragments
      of GPR56, which are generated by autocatalyzed cleavage, played distinct roles in
      regulating VEGF production and melanoma progression. Finally, consistent with its
      suppressive roles in melanoma progression, the expression levels of GPR56 are
      inversely correlated with the malignancy of melanomas in human subjects. We
      propose that components of the GPR56-mediated signaling pathway may serve as new
      targets for antiangiogenic treatment of melanoma.

PMID- 21724592
TI  - Computational reconstruction of primordial prototypes of elementary functional
      loops in modern proteins.
AB  - MOTIVATION: Enzymes are complex catalytic machines, which perform sequences of
      elementary chemical transformations resulting in biochemical function. The
      building blocks of enzymes, elementary functional loops (EFLs), possess distinct
      functional signatures and provide catalytic and binding amino acids to the
      enzyme's active sites. The goal of this work is to obtain primordial prototypes
      of EFLs that existed before the formation of enzymatic domains and served as
      their building blocks. RESULTS: We developed a computational strategy for
      reconstructing ancient prototypes of EFLs based on the comparison of sequence
      segments on the proteomic scale, which goes beyond detection of conserved
      functional motifs in homologous proteins. We illustrate the procedure by a CxxC
      containing prototype with a very basic and ancient elementary function of
      metal/metal-containing cofactor binding and redox activity. Acquiring the
      prototypes of EFLs is necessary for revealing how the original set of protein
      folds with enzymatic functions emerged in predomain evolution. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT:
      igor.berezovsky@uni.no.

PMID- 21724591
TI  - Tissue-specific prediction of directly regulated genes.
AB  - Direct binding by a transcription factor (TF) to the proximal promoter of a gene
      is a strong evidence that the TF regulates the gene. Assaying the genome-wide
      binding of every TF in every cell type and condition is currently impractical.
      Histone modifications correlate with tissue/cell/condition-specific ('tissue
      specific') TF binding, so histone ChIP-seq data can be combined with traditional
      position weight matrix (PWM) methods to make tissue-specific predictions of TF
      promoter interactions. RESULTS: We use supervised learning to train a naive Bayes
      predictor of TF-promoter binding. The predictor's features are the histone
      modification levels and a PWM-based score for the promoter. Training and testing
      uses sets of promoters labeled using TF ChIP-seq data, and we use cross
      validation on 23 such datasets to measure the accuracy. A PWM+histone naive Bayes
      predictor using a single histone modification (H3K4me3) is substantially more
      accurate than a PWM score or a conservation-based score (phylogenetic motif
      model). The naive Bayes predictor is more accurate (on average) at all
      sensitivity levels, and makes only half as many false positive predictions at
      sensitivity levels from 10% to 80%. On average, it correctly predicts 80% of
      bound promoters at a false positive rate of 20%. Accuracy does not diminish when
      we test the predictor in a different cell type (and species) from training.
      Accuracy is barely diminished even when we train the predictor without using TF
      ChIP-seq data. AVAILABILITY: Our tissue-specific predictor of promoters bound by
      a TF is called Dr Gene and is available at http://bioinformatics.org.au/drgene.
      CONTACT: t.bailey@imb.uq.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21724593
TI  - TotalReCaller: improved accuracy and performance via integrated alignment and
      base-calling.
AB  - MOTIVATION: Currently, re-sequencing approaches use multiple modules serially to
      interpret raw sequencing data from next-generation sequencing platforms, while
      remaining oblivious to the genomic information until the final alignment step.
      Such approaches fail to exploit the full information from both raw sequencing
      data and the reference genome that can yield better quality sequence reads, SNP
      calls, variant detection, as well as an alignment at the best possible location
      in the reference genome. Thus, there is a need for novel reference-guided
      bioinformatics algorithms for interpreting analog signals representing sequences
      of the bases ({A, C, G, T}), while simultaneously aligning possible sequence
      reads to a source reference genome whenever available. RESULTS: Here, we propose
      a new base-calling algorithm, TotalReCaller, to achieve improved performance. A
      linear error model for the raw intensity data and Burrows-Wheeler transform (BWT)
      based alignment are combined utilizing a Bayesian score function, which is then
      globally optimized over all possible genomic locations using an efficient branch
      and-bound approach. The algorithm has been implemented in soft- and hardware
      [field-programmable gate array (FPGA)] to achieve real-time performance.
      Empirical results on real high-throughput Illumina data were used to evaluate
      TotalReCaller's performance relative to its peers-Bustard, BayesCall, Ibis and
      Rolexa-based on several criteria, particularly those important in clinical and
      scientific applications. Namely, it was evaluated for (i) its base-calling speed
      and throughput, (ii) its read accuracy and (iii) its specificity and sensitivity
      in variant calling. AVAILABILITY: A software implementation of TotalReCaller as
      well as additional information, is available at:
      http://bioinformatics.nyu.edu/wordpress/projects/totalrecaller/ CONTACT:
      fabian.menges@nyu.edu.

PMID- 21724594
TI  - MethylCoder: software pipeline for bisulfite-treated sequences.
AB  - MOTIVATION: MethylCoder is a software program that generates per-base methylation
      data given a set of bisulfite-treated reads. It provides the option to use either
      of two existing short-read aligners, each with different strengths. It accounts
      for soft-masked alignments and overlapping paired-end reads. MethylCoder outputs
      data in text and binary formats in addition to the final alignment in SAM format,
      so that common high-throughput sequencing tools can be used on the resulting
      output. It is more flexible than existing software and competitive in terms of
      speed and memory use. AVAILABILITY: MethylCoder requires only a python
      interpreter and a C compiler to run. Extensive documentation and the full source
      code are available under the MIT license at:
      https://github.com/brentp/methylcode. CONTACT: bpederse@gmail.com.

PMID- 21724596
TI  - Exercise for intermittent claudication.

PMID- 21724597
TI  - Invited commentary.

PMID- 21724598
TI  - Molecular design of a splicing switch responsive to the RNA binding protein
      Tra2beta.
AB  - Tra2beta regulates a number of splicing switches including activation of the
      human testis-specific exon HIPK3-T in the Homeodomain Interacting Protein Kinase
      3 gene. By testing HIPK3-T exons of different intrinsic strengths, we found
      Tra2beta most efficiently activated splicing inclusion of intrinsically weak
      exons, although these were spliced at a lower overall level. Both the RRM and N
      terminal RS-rich region of Tra2beta were required for splicing activation.
      Bioinformatic searches for splicing enhancers and repressors mapped four
      physically distinct exonic splicing enhancers (ESEs) within HIPK3-T, each
      containing the known Tra2beta AGAA-rich binding site. Surprisingly disruption of
      each single ESE prevented Tra2beta-mediated activation, although single mutated
      exons could still bind Tra2beta protein by gel shifts and functional splicing
      analyses. Titration experiments indicate an additive model of HIPK3-T splicing
      activation, requiring availability of an array of four distinct ESEs to enable
      splicing activation. To enable this efficient Tra2beta-mediated splicing switch
      to operate, a closely adjacent downstream and potentially competitive stronger 5'
      splice site is actively repressed. Our data indicate that a novel arrangement of
      multiple mono-specific AGAA-rich ESEs coupled to a weak 5'-splice site functions
      as a responsive gauge. This gauge monitors changes in the specific nuclear
      concentration of the RNA binding protein Tra2beta, and co-ordinately regulates
      HIPK3-T exon splicing inclusion.

PMID- 21724599
TI  - Decoding the genome with an integrative analysis tool: combinatorial CRM Decoder.
AB  - The identification of genome-wide cis-regulatory modules (CRMs) and
      characterization of their associated epigenetic features are fundamental steps
      toward the understanding of gene regulatory networks. Although integrative
      analysis of available genome-wide information can provide new biological
      insights, the lack of novel methodologies has become a major bottleneck. Here, we
      present a comprehensive analysis tool called combinatorial CRM decoder (CCD),
      which utilizes the publicly available information to identify and characterize
      genome-wide CRMs in a species of interest. CCD first defines a set of the
      epigenetic features which is significantly associated with a set of known CRMs as
      a code called 'trace code', and subsequently uses the trace code to pinpoint
      putative CRMs throughout the genome. Using 61 genome-wide data sets obtained from
      17 independent mouse studies, CCD successfully catalogued ~12 600 CRMs (five
      distinct classes) including polycomb repressive complex 2 target sites as well as
      imprinting control regions. Interestingly, we discovered that ~4% of the
      identified CRMs belong to at least two different classes named 'multi-functional
      CRM', suggesting their functional importance for regulating spatiotemporal gene
      expression. From these examples, we show that CCD can be applied to any potential
      genome-wide datasets and therefore will shed light on unveiling genome-wide CRMs
      in various species.

PMID- 21724600
TI  - Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1
      gene causing the MELAS syndrome by tRNA import into mitochondria.
AB  - Mutations in human mitochondrial DNA are often associated with incurable human
      neuromuscular diseases. Among these mutations, an important number have been
      identified in tRNA genes, including 29 in the gene MT-TL1 coding for the
      tRNA(Leu(UUR)). The m.3243A>G mutation was described as the major cause of the
      MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke
      like episodes). This mutation was reported to reduce tRNA(Leu(UUR))
      aminoacylation and modification of its anti-codon wobble position, which results
      in a defective mitochondrial protein synthesis and reduced activities of
      respiratory chain complexes. In the present study, we have tested whether the
      mitochondrial targeting of recombinant tRNAs bearing the identity elements for
      human mitochondrial leucyl-tRNA synthetase can rescue the phenotype caused by
      MELAS mutation in human transmitochondrial cybrid cells. We demonstrate that
      nuclear expression and mitochondrial targeting of specifically designed
      transgenic tRNAs results in an improvement of mitochondrial translation,
      increased levels of mitochondrial DNA-encoded respiratory complexes subunits, and
      significant rescue of respiration. These findings prove the possibility to direct
      tRNAs with changed aminoacylation specificities into mitochondria, thus extending
      the potential therapeutic strategy of allotopic expression to address
      mitochondrial disorders.

PMID- 21724601
TI  - Elucidation of the assembly events required for the recruitment of Utp20, Imp4
      and Bms1 onto nascent pre-ribosomes.
AB  - The 90S pre-ribosome, also known as the small subunit (SSU) processome, is a
      large multisubunit particle required for the production of the 18S rRNA from a
      pre-rRNA precursor. Recently, it has been shown that the formation of this
      particle entails the initial association of the tUTP subunit with the nascent pre
      RNA and, subsequently, the binding of Rrp5/UTP-C and U3 snoRNP/UTP-B subunits in
      two independent assembly branches. However, the mode of assembly of other 90S pre
      ribosome components remains obscure as yet. In this study, we have investigated
      the assembly of three proteins (Utp20, Imp4 and Bms1) previously regarded as
      potential nucleating factors of the 90S particle. Here, we demonstrate that the
      loading of those three proteins onto the pre-rRNA takes place independently of
      Rrp5/UTP-C and, instead, occurs downstream of the tUTP and U3/UTP-B subcomplexes.
      We also demonstrate that Bms1 and Utp20 are required for the recruitment of a
      subset of proteins to nascent pre-ribosomes. Finally, we show that proteins
      associated through secondary steps condition the stability of the two assembly
      branches in partially assembled pre-ribosomes. These results provide new
      information about the functional relationships among 90S particle components and
      the events that are required for their stepwise incorporation onto the primary
      pre-rRNA.

PMID- 21724602
TI  - Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers.
AB  - Smad proteins form multimeric complexes consisting of the 'common partner' Smad4
      and receptor regulated R-Smads on clustered DNA binding sites. Deciphering how
      pathway specific Smad complexes multimerize on DNA to regulate gene expression is
      critical for a better understanding of the cis-regulatory logic of TGF-beta and
      BMP signaling. To this end, we solved the crystal structure of the dimeric Smad4
      MH1 domain bound to a palindromic Smad binding element. Surprisingly, the Smad4
      MH1 forms a constitutive dimer on the SBE DNA without exhibiting any direct
      protein-protein interactions suggesting a DNA mediated indirect readout
      mechanism. However, the R-Smads Smad1, Smad2 and Smad3 homodimerize with
      substantially decreased efficiency despite pronounced structural similarities to
      Smad4. Therefore, intricate variations in the DNA structure induced by different
      Smads and/or variant energetic profiles likely contribute to their propensity to
      dimerize on DNA. Indeed, competitive binding assays revealed that the Smad4/R
      Smad heterodimers predominate under equilibrium conditions while R-Smad
      homodimers are least favored. Together, we present the structural basis for DNA
      recognition by Smad4 and demonstrate that Smad4 constitutively homo- and
      heterodimerizes on DNA in contrast to its R-Smad partner proteins by a mechanism
      independent of direct protein contacts.

PMID- 21724603
TI  - Specific DNA structural attributes modulate platinum anticancer drug site
      selection and cross-link generation.
AB  - Heavy metal compounds have toxic and medicinal potential through capacity to form
      strong specific bonds with macromolecules, and the interaction of platinum drugs
      at the major groove nitrogen atom of guanine bases primarily underlies their
      therapeutic activity. By crystallographic analysis of transition metal-and in
      particular platinum compound-DNA site selectivity in the nucleosome core, we
      establish that steric accessibility, which is controlled by specific structural
      parameters of the double helix, modulates initial guanine-metal bond formation.
      Moreover, DNA conformational features can be linked to both similarities and
      distinctions in platinum drug adduct formation between the naked and nucleosomal
      DNA states. Notably, structures that facilitate initial platinum-guanine bond
      formation can oppose cross-link generation, rationalizing the occurrence of long
      lived therapeutically ineffective monofunctional adducts. These findings
      illuminate DNA structure-dependent reactivity and provide a novel framework for
      understanding metal-double helix interactions, which should facilitate the
      development of improved chromatin-targeting medicinal agents.

PMID- 21724604
TI  - Dynamic usage of alternative splicing exons during mouse retina development.
AB  - Alternative processing of pre-mRNA plays an important role in protein diversity
      and biological function. Previous studies on alternative splicing (AS) often
      focused on the spatial patterns of protein isoforms across different tissues.
      Here we studied dynamic usage of AS across time, during murine retina
      development. Over 7000 exons showed dynamical changes in splicing, with
      differential splicing events occurring more frequently in early development. The
      overall splicing patterns for exclusive and inclusive exons show symmetric trends
      and genes with symmetric splicing patterns that tend to have similar biological
      functions. Furthermore, we observed that within the retina, retina-enriched genes
      that are preferentially expressed at the adult stage tend to have more
      dynamically spliced exons compared to other genes, suggesting that genes
      maintaining retina homeostasis also play an important role in development via a
      series of AS events. Interestingly, the transcriptomes of retina-enriched genes
      largely reflect the retinal developmental process. Finally, we identified a
      number of candidate cis-regulatory elements for retinal AS by analyzing the
      relative occurrence of sequence motifs in exons or flanking introns. The
      occurrence of predicted regulatory elements showed strong correlation with the
      expression level of known RNA binding proteins, suggesting the high quality of
      the identified cis-regulatory elements.

PMID- 21724605
TI  - Simple and efficient synthesis of 5' pre-adenylated DNA using thermostable RNA
      ligase.
AB  - We report a simple method of enzymatic synthesis of pre-adenylated DNA
      linkers/adapters for next-generation sequencing using thermostable RNA ligase
      from Methanobacterium thermoautotrophicum (MthRnl). Using RNA ligase for the
      reaction instead of the existing chemical or T4 DNA ligase-based methods allows
      quantitative conversion of 5'-phosphorylated single-stranded DNA (ssDNA) to the
      adenylated form. The MthRnl adenylation reaction is specific for ATP and either
      ssDNA or RNA. In the presence of Mg(+2), the reaction has a pH optimum of 6.0
      6.5. Unlike reactions that use T4 DNA ligase, this protocol does not require
      synthesis of a template strand for adenylation. The high yield of the reaction
      simplifies isolation and purification of the adenylated product. Conducting the
      adenylation reaction at the elevated temperature (65 degrees C) reduces
      structural constraints, while increased ATP concentrations allow quantitative
      adenylation of DNA with a 3'-unprotected end.

PMID- 21724606
TI  - The prebiotic evolutionary advantage of transferring genetic information from RNA
      to DNA.
AB  - In the early 'RNA world' stage of life, RNA stored genetic information and
      catalyzed chemical reactions. However, the RNA world eventually gave rise to the
      DNA-RNA-protein world, and this transition included the 'genetic takeover' of
      information storage by DNA. We investigated evolutionary advantages for using DNA
      as the genetic material. The error rate of replication imposes a fundamental
      limit on the amount of information that can be stored in the genome, as mutations
      degrade information. We compared misincorporation rates of RNA and DNA in
      experimental non-enzymatic polymerization and calculated the lowest possible
      error rates from a thermodynamic model. Both analyses found that RNA replication
      was intrinsically error-prone compared to DNA, suggesting that total genomic
      information could increase after the transition to DNA. Analysis of the
      transitional RNA/DNA hybrid duplexes showed that copying RNA into DNA had similar
      fidelity to RNA replication, so information could be maintained during the
      genetic takeover. However, copying DNA into RNA was very error-prone, suggesting
      that attempts to return to the RNA world would result in a considerable loss of
      information. Therefore, the genetic takeover may have been driven by a
      combination of increased chemical stability, increased genome size and
      irreversibility.

PMID- 21724607
TI  - Structural determinants of TAR RNA-DNA annealing in the absence and presence of
      HIV-1 nucleocapsid protein.
AB  - Annealing of the TAR RNA hairpin to the cTAR DNA hairpin is required for the
      minus-strand transfer step of HIV-1 reverse transcription. HIV-1 nucleocapsid
      protein (NC) plays a crucial role by facilitating annealing of the complementary
      hairpins. To gain insight into the mechanism of NC-mediated TAR RNA-DNA
      annealing, we used structural probes (nucleases and potassium permanganate), gel
      retardation assays, fluorescence anisotropy and cTAR mutants under conditions
      allowing strand transfer. In the absence of NC, cTAR DNA-TAR RNA annealing
      depends on nucleation through the apical loops. We show that the annealing
      intermediate of the kissing pathway is a loop-loop kissing complex involving six
      base-pairs and that the apical stems are not destabilized by this loop-loop
      interaction. Our data support a dynamic structure of the cTAR hairpin in the
      absence of NC, involving equilibrium between both the closed conformation and the
      partially open 'Y' conformation. This study is the first to show that the apical
      and internal loops of cTAR are weak and strong binding sites for NC,
      respectively. NC slightly destabilizes the lower stem that is adjacent to the
      internal loop and shifts the equilibrium toward the 'Y' conformation exhibiting
      at least 12 unpaired nucleotides in its lower part.

PMID- 21724608
TI  - Role of the closing base pair for d(GCA) hairpin stability: free energy analysis
      and folding simulations.
AB  - Hairpin loops belong to the most important structural motifs in folded nucleic
      acids. The d(GNA) sequence in DNA can form very stable trinucleotide hairpin
      loops depending, however, strongly on the closing base pair. Replica-exchange
      molecular dynamics (REMD) were employed to study hairpin folding of two DNA
      sequences, d(gcGCAgc) and d(cgGCAcg), with the same central loop motif but
      different closing base pairs starting from single-stranded structures. In both
      cases, conformations of the most populated conformational cluster at the lowest
      temperature showed close agreement with available experimental structures. For
      the loop sequence with the less stable G:C closing base pair, an alternative loop
      topology accumulated as second most populated conformational state indicating a
      possible loop structural heterogeneity. Comparative-free energy simulations on
      induced loop unfolding indicated higher stability of the loop with a C:G closing
      base pair by ~3 kcal mol(-1) (compared to a G:C closing base pair) in very good
      agreement with experiment. The comparative energetic analysis of sampled
      unfolded, intermediate and folded conformational states identified electrostatic
      and packing interactions as the main contributions to the closing base pair
      dependence of the d(GCA) loop stability.

PMID- 21724609
TI  - Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription.
AB  - Autoimmune regulator (AIRE) is a transcription factor that induces the expression
      of a large subset of otherwise strictly tissue restricted antigens in medullary
      thymic epithelial cells, thereby enabling their presentation to developing T
      cells for negative selection. Mutations in AIRE lead to autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare monogenetic
      disease. Although it has been reported that AIRE interacts with proteins involved
      in nuclear transport, DNA-damage response, chromatin remodeling, transcription
      and pre-mRNA-splicing, the precise mechanism of AIRE-induced tissue restricted
      antigen expression has remained elusive. In this study, we investigated an APECED
      patient mutation that causes the loss of the extreme C-terminus of AIRE and found
      that this mutant protein is transcriptionaly inactive. When tethered
      heterologously to DNA, this domain could stimulate transcription and splicing by
      itself. Moreover, the loss of this C-terminus disrupted interactions with the
      positive transcription elongation factor b (P-TEFb). Via P-TEFb, AIRE increased
      levels of RNA polymerase II on and enhanced pre-mRNA splicing of heterologous and
      endogenous target genes. Indeed, the inhibition of CDK9, the kinase subunit of P
      TEFb, inhibited AIRE-induced pre-mRNA splicing of these genes. Thus, AIRE
      requires P-TEFb to activate transcription elongation and co-transcriptional
      processing of target genes.

PMID- 21724610
TI  - A global insight into a cancer transcriptional space using pancreatic data:
      importance, findings and flaws.
AB  - Despite the increasing wealth of available data, the structure of cancer
      transcriptional space remains largely unknown. Analysis of this space would
      provide novel insights into the complexity of cancer, assess relative
      implications in complex biological processes and responses, evaluate the
      effectiveness of cancer models and help uncover vital facets of cancer biology
      not apparent from current small-scale studies. We conducted a comprehensive
      analysis of pancreatic cancer-expression space by integrating data from otherwise
      disparate studies. We found (i) a clear separation of profiles based on
      experimental type, with patient tissue samples, cell lines and xenograft models
      forming distinct groups; (ii) three subgroups within the normal samples adjacent
      to cancer showing disruptions to biofunctions previously linked to cancer; and
      (iii) that ectopic subcutaneous xenografts and cell line models do not
      effectively represent changes occurring in pancreatic cancer. All findings are
      available from our online resource for independent interrogation. Currently, the
      most comprehensive analysis of pancreatic cancer to date, our study primarily
      serves to highlight limitations inherent with a lack of raw data availability,
      insufficient clinical/histopathological information and ambiguous data
      processing. It stresses the importance of a global-systems approach to assess and
      maximise findings from expression profiling of malignant and non-malignant
      diseases.

PMID- 21724611
TI  - MicroRNA-296 is enriched in cancer cells and downregulates p21WAF1 mRNA
      expression via interaction with its 3' untranslated region.
AB  - MicroRNAs (miRNAs) are a class of noncoding small RNAs that act as negative
      regulators of gene expression. To identify miRNAs that may regulate human cell
      immortalization and carcinogenesis, we performed comparative miRNA array
      profiling of human normal and SV40-T antigen immortalized cells. We found that
      miR-296 was upregulated in immortalized cells that also had activation of
      telomerase. By an independent experiment on genomic analysis of cancer cells we
      found that chromosome region (20q13.32), where miR-296 is located, was amplified
      in 28/36 cell lines, and most of these showed enriched miR-296 expression.
      Overexpression of miR-296 in human cancer cells, with and without telomerase
      activity, had no effect on their telomerase function. Instead, it suppressed p53
      function that is frequently downregulated during human cell immortalization and
      carcinogenesis. By monitoring the activity of a luciferase reporter connected to
      p53 and p21(WAF1) (p21) untranslated regions (UTRs), we demonstrate that miR-296
      interacts with the p21-3'UTR, and the Hu binding site of p21-3'UTR was identified
      as a potential miR-296 target site. We demonstrate for the first time that miR
      296 is frequently upregulated during immortalization of human cells and
      contributes to carcinogenesis by downregulation of p53-p21(WAF1) pathway.

PMID- 21724612
TI  - A multifactor regulatory circuit involving H-NS, VirF and an antisense RNA
      modulates transcription of the virulence gene icsA of Shigella flexneri.
AB  - The icsA gene of Shigella encodes a structural protein involved in colonization
      of the intestinal mucosa by bacteria. This gene is expressed upon invasion of the
      host and is controlled by a complex regulatory circuit involving the nucleoid
      protein H-NS, the AraC-like transcriptional activator VirF, and a 450 nt
      antisense RNA (RnaG) acting as transcriptional attenuator. We investigated on the
      interplay of these factors at the molecular level. DNase I footprints reveal that
      both H-NS and VirF bind to a region including the icsA and RnaG promoters. H-NS
      is shown to repress icsA transcription at 30 degrees C but not at 37 degrees C,
      suggesting a significant involvement of this protein in the temperature-regulated
      expression of icsA. We also demonstrate that VirF directly stimulates icsA
      transcription and is able to alleviate H-NS repression in vitro. According to
      these results, icsA expression is derepressed in hns- background and
      overexpressed when VirF is provided in trans. Moreover, we find that RnaG
      mediated transcription attenuation depends on 80 nt at its 5'-end, a stretch
      carrying the antisense region. Bases engaged in the initial contact leading to
      sense-antisense pairing have been identified using synthetic RNA and DNA
      oligonucleotides designed to rebuild and mutagenize the two stem-loop motifs of
      the antisense region.

PMID- 21724613
TI  - DNA cleavage site selection by Type III restriction enzymes provides evidence for
      head-on protein collisions following 1D bidirectional motion.
AB  - DNA cleavage by the Type III Restriction-Modification enzymes requires
      communication in 1D between two distant indirectly-repeated recognitions sites,
      yet results in non-specific dsDNA cleavage close to only one of the two sites. To
      test a recently proposed ATP-triggered DNA sliding model, we addressed why one
      site is selected over another during cleavage. We examined the relative cleavage
      of a pair of identical sites on DNA substrates with different distances to a free
      or protein blocked end, and on a DNA substrate using different relative
      concentrations of protein. Under these conditions a bias can be induced in the
      cleavage of one site over the other. Monte-Carlo simulations based on the sliding
      model reproduce the experimentally observed behaviour. This suggests that
      cleavage site selection simply reflects the dynamics of the preceding stochastic
      enzyme events that are consistent with bidirectional motion in 1D and DNA
      cleavage following head-on protein collision.

PMID- 21724614
TI  - Characterization and crystal structure of the type IIG restriction endonuclease
      RM.BpuSI.
AB  - A type IIG restriction endonuclease, RM.BpuSI from Bacillus pumilus, has been
      characterized and its X-ray crystal structure determined at 2.35A resolution. The
      enzyme is comprised of an array of 5-folded domains that couple the enzyme's N
      terminal endonuclease domain to its C-terminal target recognition and methylation
      activities. The REase domain contains a PD-x(15)-ExK motif, is closely
      superimposable against the FokI endonuclease domain, and coordinates a single
      metal ion. A helical bundle domain connects the endonuclease and
      methyltransferase (MTase) domains. The MTase domain is similar to the N6-adenine
      MTase M.TaqI, while the target recognition domain (TRD or specificity domain)
      resembles a truncated S subunit of Type I R-M system. A final structural domain,
      that may form additional DNA contacts, interrupts the TRD. DNA binding and
      cleavage must involve large movements of the endonuclease and TRD domains, that
      are probably tightly coordinated and coupled to target site methylation status.

PMID- 21724615
TI  - Identification of an hepatitis delta virus-like ribozyme at the mRNA 5'-end of
      the L1Tc retrotransposon from Trypanosoma cruzi.
AB  - L1Tc is a non-LTR LINE element from Trypanosoma cruzi that encodes its
      transposition machinery and bears an internal promoter. Herewith, we report the
      identification of an in vitro active hepatitis delta virus-like ribozyme located
      in the first 77 nt at the 5'-end of the L1Tc mRNA (L1TcRz). The data presented
      show that L1TcRz has a co-transcriptional function. Using gel-purified uncleaved
      RNA transcripts, the data presented indicate that the kinetics of the self
      cleaving, in a magnesium-dependent reaction, fits to a two-phase decay curve. The
      cleavage point identified by primer extension takes place at +1 position of the
      element. The hydroxyl nature of the 5'-end of the 3'-fragment generated by the
      cleavage activity of L1TcRz was confirmed. Since we have previously described
      that the 77-nt long fragment located at the 5'-end of L1Tc has promoter activity,
      the existence of a ribozyme in L1Tc makes this element to be the first described
      non-LTR retroelement that has an internal promoter-ribozyme dual function. The
      L1Tc nucleotides located downstream of the ribozyme catalytic motif appear to
      inhibit its activity. This inhibition may be influenced by the existence of a
      specific L1Tc RNA conformation that is recognized by RNase P.

PMID- 21724616
TI  - Specific sequence determinants of miR-15/107 microRNA gene group targets.
AB  - MicroRNAs (miRNAs) target mRNAs in human cells via complex mechanisms that are
      still incompletely understood. Using anti-Argonaute (anti-AGO) antibody co
      immunoprecipitation, followed by microarray analyses and downstream
      bioinformatics, 'RIP-Chip' experiments enable direct analyses of miRNA targets.
      RIP-Chip studies (and parallel assessments of total input mRNA) were performed in
      cultured H4 cells after transfection with miRNAs corresponding to the miR-15/107
      gene group (miR-103, miR-107, miR-16 and miR-195), and five control miRNAs. Three
      biological replicates were run for each condition with a total of 54 separate
      human Affymetrix Human Gene 1.0 ST array replicates. Computational analyses
      queried for determinants of miRNA:mRNA binding. The analyses support four major
      findings: (i) RIP-Chip studies correlated with total input mRNA profiling
      provides more comprehensive information than using either RIP-Chip or total mRNA
      profiling alone after miRNA transfections; (ii) new data confirm that miR-107
      paralogs target coding sequence (CDS) of mRNA; (iii) biochemical and
      computational studies indicate that the 3' portion of miRNAs plays a role in
      guiding miR-103/7 to the CDS of targets; and (iv) there are major sequence
      specific targeting differences between miRNAs in terms of CDS versus 3'
      untranslated region targeting, and stable AGO association versus mRNA knockdown.
      Future studies should take this important miRNA-to-miRNA variability into
      account.

PMID- 21724617
TI  - Complex life cycles and the responses of insects to climate change.
AB  - Many organisms have complex life cycles with distinct life stages that experience
      different environmental conditions. How does the complexity of life cycles affect
      the ecological and evolutionary responses of organisms to climate change? We
      address this question by exploring several recent case studies and synthetic
      analyses of insects. First, different life stages may inhabit different
      microhabitats, and may differ in their thermal sensitivities and other traits
      that are important for responses to climate. For example, the life stages of
      Manduca experience different patterns of thermal and hydric variability, and
      differ in tolerance to high temperatures. Second, life stages may differ in their
      mechanisms for adaptation to local climatic conditions. For example, in Colias,
      larvae in different geographic populations and species adapt to local climate via
      differences in optimal and maximal temperatures for feeding and growth, whereas
      adults adapt via differences in melanin of the wings and in other morphological
      traits. Third, we extend a recent analysis of the temperature-dependence of
      insect population growth to demonstrate how changes in temperature can
      differently impact juvenile survival and adult reproduction. In both temperate
      and tropical regions, high rates of adult reproduction in a given environment may
      not be realized if occasional, high temperatures prevent survival to maturity.
      This suggests that considering the differing responses of multiple life stages is
      essential to understand the ecological and evolutionary consequences of climate
      change.

PMID- 21724618
TI  - A preliminary analysis of correlations between chewing motor patterns and
      mandibular morphology across mammals.
AB  - The establishment of a publicly-accessible repository of physiological data on
      feeding in mammals, the Feeding Experiments End-user Database (FEED), along with
      improvements in reconstruction of mammalian phylogeny, significantly improves our
      ability to address long-standing questions about the evolution of mammalian
      feeding. In this study, we use comparative phylogenetic methods to examine
      correlations between jaw robusticity and both the relative recruitment and the
      relative time of peak activity for the superficial masseter, deep masseter, and
      temporalis muscles across 19 mammalian species from six orders. We find little
      evidence for a relationship between jaw robusticity and electromyographic (EMG)
      activity for either the superficial masseter or temporalis muscles across
      mammals. We hypothesize that future analyses may identify significant
      associations between these physiological and morphological variables within
      subgroups of mammals that share similar diets, feeding behaviors, and/or
      phylogenetic histories. Alternatively, the relative peak recruitment and timing
      of the balancing-side (i.e., non-chewing-side) deep masseter muscle (BDM) is
      significantly negatively correlated with the relative area of the mandibular
      symphysis across our mammalian sample. This relationship exists despite BDM
      activity being associated with different loading regimes in the symphyses of
      primates compared to ungulates, suggesting a basic association between magnitude
      of symphyseal loads and symphyseal area among these mammals. Because our sample
      primarily represents mammals that use significant transverse movements during
      chewing, future research should address whether the correlations between BDM
      activity and symphyseal morphology characterize all mammals or should be
      restricted to this "transverse chewing" group. Finally, the significant
      correlations observed in this study suggest that physiological parameters are an
      integrated and evolving component of feeding across mammals.

PMID- 21724619
TI  - Coping with variability in small neuronal networks.
AB  - Experimental and corresponding modeling studies indicate that there is a 2- to 5
      fold variation of intrinsic and synaptic parameters across animals while
      functional output is maintained. Here, we review experiments, using the heartbeat
      central pattern generator (CPG) in medicinal leeches, which explore the
      consequences of animal-to-animal variation in synaptic strength for coordinated
      motor output. We focus on a set of segmental heart motor neurons that all receive
      inhibitory synaptic input from the same four premotor interneurons. These four
      premotor inputs fire in a phase progression and the motor neurons also fire in a
      phase progression because of differences in synaptic strength profiles of the
      four inputs among segments. Our work tested the hypothesis that functional output
      is maintained in the face of animal-to-animal variation in the absolute strength
      of connections because relative strengths of the four inputs onto particular
      motor neurons is maintained across animals. Our experiments showed that relative
      strength is not strictly maintained across animals even as functional output is
      maintained, and animal-to-animal variations in strength of particular inputs do
      not correlate strongly with output phase. Further experiments measured the
      precise temporal pattern of the premotor inputs, the segmental synaptic strength
      profiles of their connections onto motor neurons, and the temporal pattern (phase
      progression) of those motor neurons all in the same animal for a series of 12
      animals. The analysis of input and output in this sample of 12 individuals
      suggests that the number (four) of inputs to each motor neuron and the
      variability of the temporal pattern of input from the CPG across individuals
      weaken the influence of the strength of individual inputs. Moreover, the temporal
      pattern of the output varies as much across individuals as that of the input.
      Essentially, each animal arrives at a unique solution for how the network
      produces functional output.

PMID- 21724620
TI  - Determination of moderate-to-severe postoperative pain on the numeric rating
      scale: a cut-off point analysis applying four different methods.
AB  - BACKGROUND: Cut-off points (CPs) of the numeric rating scale (NRS 0-10) are
      regularly used in postoperative pain treatment. However, there is insufficient
      evidence to identify the optimal CP between mild and moderate pain. METHODS: A
      total of 435 patients undergoing general, trauma, or oral and maxillofacial
      surgery were studied. To determine the optimal CP for pain treatment, four
      approaches were used: first, patients estimated their tolerable postoperative
      pain intensity before operation; secondly, 24 h after surgery, they indicated if
      they would have preferred to receive more analgesics; thirdly, satisfaction with
      pain treatment was analysed, and fourthly, multivariate analysis was used to
      calculate the optimal CP for pain intensities in relation to pain-related
      interference with movement, breathing, sleep, and mood. RESULTS: The estimated
      tolerable postoperative pain before operation was median (range) NRS 4.0 (0-10).
      Patients who would have liked more analgesics reported significantly higher
      average pain since surgery [median NRS 5.0 (0-9)] compared with those without
      this request [NRS 3.0 (0-8)]. Patients satisfied with pain treatment reported an
      average pain intensity of median NRS 3.0 (0-8) compared with less satisfied
      patients with NRS 5.0 (2-9). Analysis of average postoperative pain in relation
      to pain-related interference with mood and activity indicated pain categories of
      NRS 0-2, mild; 3-4, moderate; and 5-10, severe pain. CONCLUSIONS: Three of the
      four methods identified a treatment threshold of average pain of NRS>=4. This was
      considered to identify patients with pain of moderate-to-severe intensity. This
      cut-off was indentified as the tolerable pain threshold.

PMID- 21724621
TI  - Who presents more than once? Repeat abortion among women in Britain.
AB  - BACKGROUND AND METHODOLOGY: Around one in three sexually active women in Britain
      will have an abortion during their lifetime and a third of those women will
      experience more than one. Using data collected during the second National Survey
      of Sexual Attitudes and Lifestyles the characteristics of women who have
      presented for a second or subsequent abortion are compared to those women who
      have obtained only one. RESULTS: Results indicate that increased age and parity
      are key characteristics distinguishing between women who have experienced only
      one abortion and those women who have had more. Findings also reveal that those
      who have sought abortion on more than one occasion are more likely (than those
      who have had one abortion) to be Black, have left school at an earlier age, be
      living in rented accommodation, report an earlier age at first sexual experience,
      be less likely to have used a reliable method of contraception at sexual debut
      and report a greater number of sexual partners. DISCUSSION AND CONCLUSIONS: It is
      well recognised that attendance at abortion services presents an important
      opportunity for the provision of individually tailored information regarding
      contraception to assist women avoid the need for subsequent procedures. However,
      differential use of abortion services may also indicate variations in knowledge
      levels, attitudes to risk, attitudes towards abortion, partner communication,
      gender power and differential access to services. Further research is required to
      clarify these potential relationships so that suitable health promotion
      activities can be developed.

PMID- 21724622
TI  - AKT signalling in the failing heart.
AB  - AKT is a serine/threonine protein kinase, also known as protein kinase B, which
      regulates cardiac growth, myocardial angiogenesis, glucose metabolism, and cell
      death in cardiac myocytes. AKT is activated by its phosphorylation at Thr 308 and
      ser 473 by PDK1 and mTORC2, respectively, in response to trophic stimuli such as
      insulin and insulin growth factor. c-Jun N-Terminal Kinases (JNKs) phosphorylate
      AKT at Thr 450 and potentiate its interaction with its downstream effectors. The
      short-term activation of AKT promotes physiological hypertrophy and protection
      from myocardial injury; whereas, its long-term activation causes pathological
      hypertrophy and heart failure. In this review we will discuss the role of AKT in
      regulating signalling pathways in the heart with special emphasis on the role of
      AKT in modulating stress induced autophagic cell death in cardiomyocytes in
      vitro.

PMID- 21724623
TI  - Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome
      patients: RADAR pharmacokinetic and pharmacodynamic substudy.
AB  - AIMS: Establishing factor IX inhibition in patients with acute coronary
      syndrome/non-ST-elevation myocardial infarction (ACS/NSTEMI), a setting
      characterized by increased factor IX activity, is critical to investigate the
      REG1 system in this target population. The REG1 system (Regado Biosciences,
      Basking Ridge, NJ) consists of pegnivacogin (RB006), an RNA aptamer that directly
      inhibits factor IXa, and anivamersen (RB007), its complementary control agent.
      METHODS AND RESULTS: RADAR is a Phase 2b study investigating the use of
      pegnivacogin in patients (n = 800) with ACS undergoing planned early cardiac
      catheterization. To validate dose selection and stability of anticoagulation
      throughout the time of cardiac catheterization at an early stage of the clinical
      trial, 33 patients, 22 of whom had not received recent prior heparin, underwent
      thorough pharmacokinetic and pharmacodynamic assessment. Fold prolongation of
      activated partial thromboplastin time (aPTT) was used to impute factor IX
      inhibition. Pegnivacogin 1 mg/kg rapidly achieved a high pegnivacogin plasma
      concentration (26.1 +/- 4.6 ug/mL), prolonged the aPTT (mean aPTT 93.0 +/- 9.5
      s), and approached near complete factor IX inhibition (mean fold increase from
      baseline 2.9 +/- 0.3). These levels remained stable from the time of drug
      administration through completion of the catheterization. CONCLUSION:
      Pegnivacogin administered at a weight-adjusted dose of 1 mg/kg consistently
      achieves a high level of factor IX activity inhibition among patients with ACS
      and provides stable anticoagulation during cardiac catheterization. These
      findings support the dose of pegnivacogin selected for the RADAR study.

PMID- 21724624
TI  - Myeloperoxidase deficiency preserves vasomotor function in humans.
AB  - AIMS: Observational studies have suggested a mechanistic link between the
      leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we
      tested whether MPO is systemically affecting vascular tone in humans. METHODS AND
      RESULTS: A total of 12 135 patients were screened for leucocyte peroxidase
      activity. We identified 15 individuals with low MPO expression and activity
      (MPO(low)), who were matched with 30 participants exhibiting normal MPO protein
      content and activity (control). Nicotine-dependent activation of leucocytes
      caused attenuation of endothelial nitric oxide (NO) bioavailability in the
      control group (P < 0.01), but not in MPO(low) individuals (P = 0.12); here the
      MPO burden of leucocytes correlated with the degree of vasomotor dysfunction (P =
      0.008). To directly test the vasoactive properties of free circulating MPO, the
      enzyme was injected into the left atrium of anaesthetized, open-chest pigs.
      Myeloperoxidase plasma levels peaked within minutes and rapidly declined
      thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior
      descending artery and the internal mammary artery (IMA) as well as myocardial
      perfusion decreased following MPO injection when compared with albumin-treated
      animals (P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed
      markedly diminished relaxation in response to acetylcholine (P < 0.01) and
      nitroglycerine as opposed to controls (P < 0.001). CONCLUSION: Myeloperoxidase
      elicits profound effects on vascular tone of conductance and resistance vessels
      in vivo. These findings not only call for revisiting the biological functions of
      leucocytes as systemic and mobile effectors of vascular tone, but also identify
      MPO as a critical systemic regulator of vasomotion in humans and thus a potential
      therapeutic target.

PMID- 21724625
TI  - A long way from Cape Town: a personal and professional journey from South Africa
      to the USA.
AB  - Rhodes Scholar Bernard J. Gersh moved to the Mayo Clinic,Rochester, Minnesota,
      via Oxford University, embraced a new culture and speaks to Judy Ozkan.

PMID- 21724626
TI  - Defining and measuring health literacy: how can we profit from other literacy
      domains?
AB  - When the antecedents of health-promoting behavior are explored, the concept of
      health literacy is deemed a factor of major influence. Originally defined as
      reading, writing and numeracy skills in the health domain, health literacy is now
      considered a multidimensional concept. The ongoing discussion on health literacy
      reveals that no agreement exists about which dimensions to include in the
      concept. To contribute to the development of a consistent and parsimonious
      concept of health literacy, we conducted a critical review of concepts in other
      literacy domains. Our review was guided by two research questions: (i) Which
      dimensions are included in the concepts of other literacy domains? (ii) How can
      health literacy research profit from other literacy domains? Based on articles
      collected from PubMed, PsycINFO, Communication & Mass Media Complete, CINAHL,
      SAGE Full-Text Collection, Cochrane Library and Google Scholar as well as
      selected monographs and editions, we identified seven distinct dimensions. Some
      of the dimensions recur across all reviewed literacy domains and first attempts
      have been made to operationalize the dimensions. Expanding upon these dimensions,
      the paper discusses how they can prove useful for elaborating a consistent and
      parsimonious concept of health literacy and foster the development of a more
      holistic measure.

PMID- 21724627
TI  - Measuring intrabladder pressure with the head of the bed elevated 30 degrees :
      evidence to support a change in practice.
AB  - BACKGROUND: A 30 degrees  head-of-bed elevation is recommended for most
      critically ill patients. Measuring intrabladder pressure with the patient in this
      position is controversial. OBJECTIVE: To assess the feasibility of measuring
      intrabladder pressure with a 30 degrees  head-of-bed elevation. METHODS: A
      prospective, randomized, and experimental study. Patients had intrabladder
      pressure measured first while positioned supine with a 30 degrees  head-of-bed
      elevation and 25 mL of saline instilled into the bladder and again after the
      patients were randomly repositioned to supine without any head-of-bed elevation
      (flat) or with a 30 degrees  head-of-bed elevation while supine or in right
      lateral or left lateral position with either 25, 50, or 200 mL of saline
      instilled into the patient's bladder. RESULTS: Intrabladder pressures measured
      with the patient in all 3 head-of-bed elevated positions were higher than
      pressures measured with patients supine and flat after instillation of 25 mL of
      saline into the bladder, but intrabladder pressure did not differ between the 30
      degrees  head-of-bed elevated positions and the supine and flat positions when 50
      or 200 mL of saline was instilled into the bladder. Two-way analysis of variance
      showed a significant interaction between volume of saline instilled (P = .05),
      patient's position (P = .007), and bladder instill volume and position
      interaction (P = .004). CONCLUSION: It is feasible to measure intrabladder
      pressure with a 30 degrees  head-of-bed elevation, and that position could be an
      alternative to supine positioning of patients for measurement of intrabladder
      pressure.

PMID- 21724628
TI  - Daily interruption of sedation in patients receiving mechanical ventilation.
AB  - BACKGROUND: Daily interruption of continuous infusion of sedatives has improved
      outcomes in patients receiving mechanical ventilation in open-label studies.
      OBJECTIVES: To assess the feasibility of a protocol for a double-blind,
      randomized, controlled trial study on the impact of routine daily interruption of
      sedation in patients receiving mechanical ventilation. METHODS: A total of 50
      patients receiving mechanical ventilation were randomized to daily interruption
      of fentanyl and/or midazolam infusions for up to 6 hours or to usual management
      of sedation. Blinding was achieved by using replacement infusions (saline or
      active drug in saline). RESULTS: The recruitment target of 80 patients was not
      met in an extended time frame. Propofol was used outside the protocol in 27% of
      patients in the intervention group and 17% of patients in the control group (P =
      .10). A total of 15% of the intervention group and 12% of the control group never
      had replacement infusions started (P = .77), and replacement infusions were
      started on only approximately one-third of eligible days in patients who received
      replacement infusions. The mean doses of fentanyl and midazolam were similar. The
      blinding strategy was safe and effective: no patients had unplanned extubations,
      and the most frequent reason for ending replacement infusions was completion of
      the maximum 6-hour period. CONCLUSIONS: The double-blinded design for assessment
      of sedation interruption in patients receiving mechanical ventilation was safe
      and effective. Slow recruitment of patients and frequent noncompliance with the
      protocol suggest that modifications to the protocol are needed.

PMID- 21724629
TI  - Resource document: evidence supporting current practice in timing assessment.

PMID- 21724630
TI  - Scalpel, stethoscope, iPad: the future is now in the intensive care unit.

PMID- 21724632
TI  - As health care technology advances: benefits and risks.
AB  - Technology permeates every dimension of critical care. Bedside technology is
      integral to the assessment and monitoring of patients and to the provision of
      treatment. It also helps with access to vital information and can enhance
      communication. Although it offers extraordinary benefits to patients and
      clinicians, technology may also create problems. Our research addresses the wise
      use of technology in the care of critically ill patients. It examines the
      appropriate and safe use of technology, its equitable distribution, and the human
      machine interface. Given that some devices are more effective and safe than
      others, it is important to assess the appropriateness of a specific technology in
      a specific situation. Just because a particular device is available, is it
      necessary to use it in every possible situation? Do we use it just because it is
      there? Do we employ "heroic" measures sometimes when it would be kinder not to?
      Studies on the safe use of technology in patient care lead to a consideration of
      the risk-benefit ratio. Our research on gender and racial differences in the use
      of cardiac procedures in patients with acute myocardial infarction focused on the
      equitable distribution of technology. The results of this line of research, along
      with those of numerous other studies, suggest possible racism in our health care
      practices. The human-machine interface, or how clinicians and patients interact
      with health care technology, is a crucial focus of research. Technology is at the
      heart of critical care. It allows clinicians to perform miracles, but is also a
      seductive and self-perpetuating force that needs careful monitoring by those who
      use it.

PMID- 21724633
TI  - Psychophysiological determinants of repeated ventilator weaning failure: an
      explanatory model.
AB  - BACKGROUND: The adverse effects of a failed ventilator weaning trial on the
      subsequent weaning attempts are not well understood. OBJECTIVES: To examine
      physiological and psychological factors that may be predictive of risk for
      repeated weaning failures and prolonged mechanical ventilation. METHODS: A
      prospective predictive study of 102 subjects, age 34 to 91 years, whose first
      ventilator weaning trial was unsuccessful but who were physiologically ready for
      another weaning attempt. Subjects were recruited from intensive care units and a
      respiratory care center of a tertiary medical center. Validated self-report
      scales and a Bicore monitoring system were used to measure ventilator patients'
      psychophysiological performance during the second weaning trial. Structural
      equation modeling was used to analyze the data and test the model. RESULTS:
      Significant causal pathways were found between fear and anxiety (r = 0.77; P <
      .001), anxiety and respiratory function (r = 0.24; P < .05), and respiratory
      function and weaning outcomes (r = 0.42; P < .001). The overall model predicted
      that both physiological and psychological factors were important in determining
      repeated failure of ventilator weaning, and the data were in support of the model
      (chi(2) = 29.49, P > .05). CONCLUSIONS: Patients whose first ventilator weaning
      trial is unsuccessful may be markedly fearful. Left unaddressed, these fears
      cause high anxiety levels that significantly compromise respiratory function and
      contribute to subsequent weaning failures. Thus begins a vicious cycle of
      repeated failure of ventilator weaning and prolonged mechanical ventilation.

PMID- 21724634
TI  - The role of standardized protocols in unplanned extubations in a medical
      intensive care unit.
AB  - BACKGROUND: Many patients admitted to medical intensive care units require
      mechanical ventilation to assist with respiratory management. Unplanned
      extubations of these patients are associated with poor outcomes for patients and
      organizations. No previous research has investigated the role of standardized
      protocols in unplanned extubations when examined in conjunction with traditional
      risk factors. OBJECTIVE: To identify risk factors associated with unplanned
      extubation among patients receiving mechanical ventilation and determine degree
      of compliance with pain, sedation, and weaning protocols. METHODS: A prospective
      cohort study design was used. Data on all patients admitted to the medical
      intensive care unit who required mechanical ventilation were gathered daily.
      Additional data were gathered on those patients who experienced unplanned
      extubation. Descriptive, correlational, and regression analyses were performed.
      RESULTS: Weaning protocols were a significant predictor of unplanned extubation:
      patients who had weaning protocols ordered and followed were least likely to
      experience unplanned extubation. Only 10% of the 190 patients in the study
      required reintubation, resulting in a significantly shorter ventilation time and
      unit length of stay among the unplanned extubation group. CONCLUSIONS: Weaning
      protocols were associated with decreased incidence of unplanned extubation. Use
      of standardized protocols was feasible, as compliance among health care providers
      was high when protocols were medically prescribed. The reintubation rate in this
      study was low and associated with a significantly shorter ventilatory period and
      unit length of stay in the unplanned extubation group.

PMID- 21724635
TI  - Impact of protocol watch on compliance with the surviving sepsis campaign.
AB  - PURPOSE: Clinical decision support systems are intended to improve patients' care
      and outcomes, particularly when such systems are present at the point of care.
      Protocol Watch was developed as a bedside clinical decision support system to
      improve clinicians' adherence to the Surviving Sepsis Campaign guidelines. This
      pre/post-intervention pilot study was done to evaluate the effect of Protocol
      Watch on compliance with 5 guidelines from the Surviving Sepsis Campaign.
      METHODS: Preintervention data on rates and time to complete the resuscitation and
      management bundles from the Surviving Sepsis Campaign and time to administer
      antibiotics were collected from intensive care units at 2 large teaching
      hospitals in the United States. Training on the Protocol Watch application was
      then provided to clinical staff in the units, and Protocol Watch was installed at
      all critical care beds in both hospitals. Data were collected on rates and time
      to completion for 5 Surviving Sepsis Campaign guidelines after installation of
      Protocol Watch, and univariate analyses were done to evaluate the effect of
      Protocol Watch on compliance with the guidelines. RESULTS: Implementation of
      Protocol Watch was associated with significant improvements in compliance with
      the resuscitation bundle (P = .01) and decreased time to administer antibiotics
      (P = .006). No significant changes were achieved for compliance with the
      management bundle or time to complete the resuscitation or management bundles.
      CONCLUSIONS: Clinical decision support systems such as Protocol Watch may improve
      adherence to the Surviving Sepsis Campaign guidelines, which potentially may
      contribute to reduced morbidity and mortality for critically ill patients with
      sepsis.

PMID- 21724636
TI  - Intra-aortic balloon pump timing: review of evidence supporting current practice.
AB  - Intra-aortic balloon counterpulsation is the most widely used therapy for support
      of a compromised left ventricle. The principles of counterpulsation were
      developed in the 1950s, and intra-aortic balloon pumps have been used for more
      than 40 years. Despite this long-standing clinical use, many of the timing
      practices have continued almost unchanged from their inception. One of the most
      important aspects of the pumps is timing, or synchronizing the action of the
      device with the cardiac cycle. The principles of timing are based on the
      physiological objectives of counterpulsation; however, research into alternative
      timing methods has led to conflicting and often confusing information on the
      appropriate timing method for a specific clinical situation or patient. Although
      a body of knowledge is available, much of the research is dated and covers only
      specific timing methods or populations of patients. Further evidence is needed to
      support the selection of timing methods and determine the clinical benefits of
      the various methods.

PMID- 21724637
TI  - Blood cultures and central catheters: is the "easiest way" best practice?

PMID- 21724638
TI  - Computerized algorithms.

PMID- 21724639
TI  - Tubing misconnections.

PMID- 21724640
TI  - Accidental intraventricular administration of phenytoin through an external
      ventricular drain: case report.
AB  - A 52-year-old man with an external ventricular drain was transferred from the
      local neurosurgical intensive care unit to the general intensive care unit for
      renal replacement therapy. While the patient was in the general intensive care
      unit, phenytoin was accidentally administered via the external ventricular drain.
      Tachycardia and hypertension ensued and then seizure activity. The drain was
      aspirated and then washed out. Propofol was infused for 24 hours and then was
      stopped to allow continuing neurological assessment. The route of administration
      of phenytoin was changed from intravenous to oral, and care continued as before.
      After resolution of the renal failure, the patient was returned to the
      neurological intensive care unit. He recovered slowly and had no adverse effects
      due to the error in administration of phenytoin.

PMID- 21724641
TI  - Structure of human lysine methyltransferase Smyd2 reveals insights into the
      substrate divergence in Smyd proteins.
AB  - The SET- and myeloid-Nervy-DEAF-1 (MYND)-domain containing (Smyd) lysine
      methyltransferases 1-3 share relatively high sequence similarity but exhibit
      divergence in the substrate specificity. Here we report the crystal structure of
      the full-length human Smyd2 in complex with S-adenosyl-L-homocysteine (AdoHcy).
      Although the Smyd1-3 enzymes are similar in the overall structure, detailed
      comparisons demonstrate that they differ substantially in the potential substrate
      binding site. The binding site of Smyd3 consists mainly of a deep and narrow
      pocket, while those of Smyd1 and Smyd2 consist of a comparable pocket and a long
      groove. In addition, Smyd2, which has lysine methyltransferase activity on
      histone H3-lysine 36, exhibits substantial differences in the wall of the
      substrate-binding pocket compared with those of Smyd1 and Smyd3 which have
      activity specifically on histone H3-lysine 4. The differences in the substrate
      binding site might account for the observed divergence in the specificity and
      methylation state of the substrates. Further modeling study of Smyd2 in complex
      with a p53 peptide indicates that mono-methylation of p53-Lys(372) might result
      in steric conflict of the methyl group with the surrounding residues of Smyd2,
      providing a structural explanation for the inhibitory effect of the SET7/9
      mediated mono-methylation of p53-Lys(372) on the Smyd2-mediated methylation of
      p53-Lys(370).

PMID- 21724642
TI  - Recent developments in the intellectual history of medicine: a special issue of
      the Journal of the History of Medicine.

PMID- 21724643
TI  - Expanding women's rural medical work in early modern Brittany: the Daughters of
      the Holy Spirit.
AB  - During the eighteenth century, orders of nursing sisters took on an expanded role
      in the rural areas of Brittany. This article explores the impact of religious
      change on the medical activities of these women. While limits were placed on the
      medical practice of unlicensed individuals, areas of new opportunity for nuns as
      charitable practitioners were created by devout nobles throughout the eighteenth
      century. These nuns provided comprehensive care for the sick poor on their
      patrons' estates, acting not only as nurses, but also in lieu of physicians,
      surgeons, and apothecaries. This article argues that the medical knowledge and
      expertise of these sisters from the nursing orders were highly valued by the
      elites of early modern Brittany.

PMID- 21724644
TI  - Fordism in the hospital: Albert Kahn and the design of Old Main, 1917-25.
AB  - The 1917-25 planning and construction at the University of Michigan of a new
      University Hospital, later dubbed Old Main, offers a noteworthy case study of the
      formal convergence of hospital and factory in early twentieth-century America.
      Designed by Albert Kahn, the architect responsible for Ford Motor Company's
      archetypal automobile plants, and located in Ann Arbor, Michigan, less than forty
      miles from Detroit's burgeoning factory landscape, Old Main was well positioned
      to reflect the values of industry in both appearance and operation. The
      building's outer surface represents a striking departure from the historicism
      that characterized several other hospitals of this period, while plans for the
      building's novel diagnostic unit demonstrate unique operational parallels to the
      assembly line model of production. Ultimately, Old Main's industrial design
      similarities cast it as a precociously modernist hospital, relating streamlined
      form to function more explicitly than many of its contemporary institutions.

PMID- 21724648
TI  - Realizing Major William Borden's dream: military medicine, Walter Reed Army
      Medical Center, and its wounded warriors, 1909-2009: an essay review.
AB  - This essay review examines three books dealing with the founding and subsequent
      activities of Walter Reed Army Medical Center (WRAMC) and the evolution of
      military medicine from 1909 to 2009 recently published by the US Army's Borden
      Institute. Established by fellow army doctor William Borden to honor Walter Reed
      himself, WRAMC, located in Washington, DC, soon became the public and
      professional face of medical care for American soldiers. The discussion
      highlights the ongoing issue of the care and treatment of combat amputees;
      aspects of gender within military medicine; and WRAMC's function as an
      educational and research facility. Also discussed are the archival and
      documentary bases for these books and their utility for historians. Complimentary
      analysis of two of the books which are, in particular, explicitly about the
      history of WRAMC is contextualized within the celebration of the centennial of
      this army post contemporaneously with its closure, amalgamation, and relocation
      primarily to Maryland.

PMID- 21724649
TI  - Comparison of a molecular dynamics model with the X-ray structure of the N370S
      acid-beta-glucosidase mutant that causes Gaucher disease.
AB  - Recently, two studies were published that examined the structure of the acid-beta
      glucosidase N370S mutant, the most common mutant that causes Gaucher disease. One
      study used the experimental tool of X-ray crystallography, and the other utilized
      molecular dynamics (MD). The two studies reinforced each other through the
      similarities in their findings, but each approach also added some unique
      information. Both studies report that the conformation of active site loop 3
      changes, due to an altered hydrogen bonding network; however, the MD study
      produced additional data concerning the flexibility of loop 1 and the catalytic
      residues that are not observed in the other study.

PMID- 21724650
TI  - Trends in hospital admissions for sunburn in Western Australia, 1988 to 2008.
AB  - The objective of this study was to assess the trends in hospitalization for
      sunburn in Western Australia from 1988 to 2008. De-identified linked hospital
      morbidity data for all index sunburn admissions in Western Australia for the
      period 1988 to 2008 were analyzed. Poisson regression analysis was used to
      estimate trends in hospital admissions. Hospitalizations increased from 1.6 (95%
      confidence interval [CI] = 1.0-2.2) per 100 000 person years in 1988 to 2.7 (95%
      CI = 1.9-3.4) per 100 000 person years in 1997, declining thereafter to 1.5 (95%
      CI = 1.0-2.0) per 100 000 person years in 2008. Increased hospitalizations rates
      were estimated for adults 25 to 44 years and 65 years or older, with a
      significant decline estimated for children younger than 5 years; rates remained
      stable for all other age groups. This study found no significant overall
      reduction in sunburn hospitalizations over the 20-year study period. RESULTS:
      raise concerns about the sun-protective behaviors and skin cancer risk of the
      population in Western Australia.

PMID- 21724651
TI  - A small-molecule IAP inhibitor overcomes resistance to cytotoxic therapies in
      malignant gliomas in vitro and in vivo.
AB  - We tested the use of the small-molecule Inhibitor of Apoptosis Protein (IAP)
      inhibitor LBW242 in combination with the standard-of-care therapies of
      irradiation and temozolomide for malignant gliomas. In vitro assays demonstrated
      that LBW242 enhanced the cytotoxic activity of radiotherapy, and clonogenic
      assays showed that the combination therapy led to a synergistic anti-glioma
      effect in multiple cell lines. Neurosphere assays revealed that the combination
      of radiation and LBW242 led to a pro-apoptotic effect in these glioma-initiating
      cell-enriched assays, with a corresponding inhibition of primary tumor cell
      growth. Athymic mice bearing established human malignant glioma tumor xenografts
      treated with LBW242 plus radiation and temozolomide demonstrated a synergistic
      suppression of tumor growth. Taken together, these experiments show that the pro
      apoptotic and anti-glioma effects of radiotherapy and chemotherapy can be
      enhanced by the addition of a small-molecule IAP inhibitor. These results are
      readily translatable to clinical trial and offer the potential for improved
      treatment outcomes for patients with glioma.

PMID- 21724652
TI  - Left atrial 'sludge' during vagally mediated pause triggered by pulmonary vein
      antral ablation.
AB  - We report a case of a patient with long-standing persistent atrial fibrillation
      (AF) who had rapid formation of spontaneous echo-contrast in the left atrium
      during pulmonary vein antrum isolation set off by a vagally mediated pause
      despite standard anticoagulation protocol. Spontaneous echo contrast resolved
      with ventricular pacing, representing visual evidence for dependence of some AF
      patients with poor atrial transport function on ventricular emptying with
      potential greater risk of thromboembolism related to a long ventricular pause.

PMID- 21724653
TI  - Towards aspect-oriented functional--structural plant modelling.
AB  - BACKGROUND AND AIMS: Functional-structural plant models (FSPMs) are used to
      integrate knowledge and test hypotheses of plant behaviour, and to aid in the
      development of decision support systems. A significant amount of effort is being
      put into providing a sound methodology for building them. Standard techniques,
      such as procedural or object-oriented programming, are not suited for clearly
      separating aspects of plant function that criss-cross between different
      components of plant structure, which makes it difficult to reuse and share their
      implementations. The aim of this paper is to present an aspect-oriented
      programming approach that helps to overcome this difficulty. METHODS: The L
      system-based plant modelling language L+C was used to develop an aspect-oriented
      approach to plant modelling based on multi-modules. Each element of the plant
      structure was represented by a sequence of L-system modules (rather than a single
      module), with each module representing an aspect of the element's function.
      Separate sets of productions were used for modelling each aspect, with context
      sensitive rules facilitated by local lists of modules to consider/ignore. Aspect
      weaving or communication between aspects was made possible through the use of
      pseudo-L-systems, where the strict-predecessor of a production rule was specified
      as a multi-module. KEY RESULTS: The new approach was used to integrate previously
      modelled aspects of carbon dynamics, apical dominance and biomechanics with a
      model of a developing kiwifruit shoot. These aspects were specified independently
      and their implementation was based on source code provided by the original
      authors without major changes. CONCLUSIONS: This new aspect-oriented approach to
      plant modelling is well suited for studying complex phenomena in plant science,
      because it can be used to integrate separate models of individual aspects of
      plant development and function, both previously constructed and new, into clearly
      organized, comprehensive FSPMs. In a future work, this approach could be further
      extended into an aspect-oriented programming language for FSPMs.

PMID- 21724654
TI  - Apomixis is not prevalent in subnival to nival plants of the European Alps.
AB  - BACKGROUND AND AIMS: High alpine environments are characterized by short growing
      seasons, stochastic climatic conditions and fluctuating pollinator visits. These
      conditions are rather unfavourable for sexual reproduction of flowering plants.
      Apomixis, asexual reproduction via seed, provides reproductive assurance without
      the need of pollinators and potentially accelerates seed development. Therefore,
      apomixis is expected to provide selective advantages in high-alpine biota.
      Indeed, apomictic species occur frequently in the subalpine to alpine grassland
      zone of the European Alps, but the mode of reproduction of the subnival to nival
      flora was largely unknown. METHODS: The mode of reproduction in 14 species
      belonging to seven families was investigated via flow cytometric seed screen. The
      sampling comprised 12 species typical for nival to subnival plant communities of
      the European Alps without any previous information on apomixis (Achillea atrata,
      Androsace alpina, Arabis caerulea, Erigeron uniflorus, Gnaphalium hoppeanum,
      Leucanthemopsis alpina, Oxyria digyna, Potentilla frigida, Ranunculus alpestris,
      R. glacialis, R. pygmaeus and Saxifraga bryoides), and two high-alpine species
      with apomixis reported from other geographical areas (Leontopodium alpinum and
      Potentilla crantzii). KEY RESULTS: Flow cytometric data were clearly
      interpretable for all 46 population samples, confirming the utility of the method
      for broad screenings on non-model organisms. Formation of endosperm in all
      species of Asteraceae was documented. Ratios of endosperm : embryo showed
      pseudogamous apomixis for Potentilla crantzii (ratio approx. 3), but sexual
      reproduction for all other species (ratios approx. 1.5). CONCLUSIONS: The
      occurrence of apomixis is not correlated to high altitudes, and cannot be readily
      explained by selective forces due to environmental conditions. The investigated
      species have probably other adaptations to high altitudes to maintain
      reproductive assurance via sexuality. We hypothesize that shifts to apomixis are
      rather connected to frequencies of polyploidization than to ecological
      conditions.

PMID- 21724655
TI  - The good, the bad and the flexible: plant interactions with pollinators and
      herbivores over space and time are moderated by plant compensatory responses.
AB  - BACKGROUND AND AIMS: Plants are sessile organisms that face selection by both
      herbivores and pollinators. Herbivores and pollinators may select on the same
      traits and/or mediate each others' effects. Erysimum capitatum (Brassicaceae) is
      a widespread and variable plant species with generalized pollination that is
      attacked by a number of herbivores. The following questions were addressed. (a)
      Are pollinators and herbivores attracted by similar plant traits? (b) Does
      herbivory affect pollinator preferences? (c) Do pollinators and/or herbivores
      affect fitness and select on plant traits? (d) Do plant compensatory responses
      affect the outcome of interactions among plants, pollinators and herbivores? (e)
      Do interactions among E. capitatum and its pollinators and herbivores differ
      among sites and years? METHODS: In 2005 and 2006, observational and experimental
      studies were combined in four populations at different elevations to examine
      selection by pollinators and herbivores on floral traits of E. capitatum. KEY
      RESULTS: Pollinator and herbivore assemblages varied spatially and temporally, as
      did their effects on plant fitness and selection. Both pollinators and herbivores
      preferred plants with more flowers, and herbivory sometimes reduced pollinator
      visitation. Pollinators did not select on plant traits in any year or population
      and E. capitatum was not pollen limited; however, supplemental pollen resulted in
      altered plant resource allocation. Herbivores reduced fitness and selected for
      plant traits in some populations, and these effects were mediated by plant
      compensatory responses. CONCLUSIONS: Individuals of Erysimum capitatum are
      visited by diverse groups of pollinators and herbivores that shift in abundance
      and importance in time and space. Compensatory reproductive mechanisms mediate
      interactions with both pollinators and herbivores and may allow E. capitatum to
      succeed in this complex selective environment.

PMID- 21724656
TI  - Modelling the effect of wheat canopy architecture as affected by sowing density
      on Septoria tritici epidemics using a coupled epidemic-virtual plant model.
AB  - BACKGROUND AND AIMS: The relationship between Septoria tritici, a splash
      dispersed disease, and its host is complex because of the interactions between
      the dynamic plant architecture and the vertical progress of the disease. The aim
      of this study was to test the capacity of a coupled virtual wheat-Septoria
      tritici epidemic model (Septo3D) to simulate disease progress on the different
      leaf layers for contrasted sowing density treatments. METHODS: A field experiment
      was performed with winter wheat 'Soissons' grown at three contrasted densities.
      Plant architecture was characterized to parameterize the wheat model, and disease
      dynamic was monitored to compare with simulations. Three simulation scenarios,
      differing in the degree of detail with which plant variability of development was
      represented, were defined. KEY RESULTS: Despite architectural differences between
      density treatments, few differences were found in disease progress; only the
      lower-density treatment resulted in a slightly higher rate of lesion development.
      Model predictions were consistent with field measurements but did not reproduce
      the higher rate of lesion progress in the low density. The canopy reconstruction
      scenario in which inter-plant variability was taken into account yielded the best
      agreement between measured and simulated epidemics. Simulations performed with
      the canopy represented by a population of the same average plant deviated
      strongly from the observations. CONCLUSIONS: It was possible to compare the
      predicted and measured epidemics on detailed variables, supporting the hypothesis
      that the approach is able to provide new insights into the processes and plant
      traits that contribute to the epidemics. On the other hand, the complex and
      dynamic responses to sowing density made it difficult to test the model precisely
      and to disentangle the various aspects involved. This could be overcome by
      comparing more contrasted and/or simpler canopy architectures such as those
      resulting from quasi-isogenic lines differing by single architectural traits.

PMID- 21724657
TI  - Factors associated with frequent psychiatric admissions in a general hospital in
      Spain.
AB  - OBJECTIVES: To identify demographic or clinical factors associated with frequent
      admissions in a sample of patients admitted to an acute psychiatric
      hospitalization unit, controlling for potentially confounding factors. METHODS:
      Socio-demographic variables, diagnosis, and the legal status, date and length of
      admission were collected for 1,722 consecutively admitted psychiatric patients
      during a period of up to eight years (1998-2005). Frequently admitted patients
      were defined as undergoing one or more admissions per year on average. RESULTS:
      After controlling for potential confounding factors, logistic regression showed
      that being a frequently admitted patient was significantly associated with
      diagnoses of schizoaffective disorder, personality disorder or schizophrenia; an
      involuntary commitment at first admission; and younger age. CONCLUSIONS: Factors
      associated with frequently admitted patients should be identified in order to
      establish more effective strategies for preventing relapse.

PMID- 21724658
TI  - Bilateral popliteal artery entrapment syndrome with asynchronous onset.
AB  - Popliteal artery entrapment syndrome is recognized as a cause of lower leg
      claudication in patients younger than 50 years of age. We report a rare case of a
      patient with bilateral popliteal artery entrapment who presented with the same
      symptom 11 years after his first experience of popliteal artery entrapment
      syndrome. On both occasions, the surgery was performed in a similar manner and
      the patient was free from symptoms after the surgery. Since the diagnosis of
      popliteal artery entrapment syndrome is difficult, early detection of popliteal
      artery entrapment syndrome is important to prevent its progression.

PMID- 21724660
TI  - One-stage total thoracic aortic repair for mega-aorta using frozen elephant trunk
      technique.
AB  - We report the case of a 71-year-old female with mega-aorta extending from the
      ascending aorta to the descending aorta, who was successfully treated with a one
      stage total thoracic aortic repair by the frozen elephant trunk technique using a
      stent-graft. We used a home-made frozen elephant trunk with four giant-turco Z
      stents on the distal side that was inserted into the downstream descending aorta
      via an aortic arch guiding pull-through wire. The stent-graft was distally
      positioned at the level of the 12th thoracic vertebra after total arch
      replacement had been performed using a four-branch graft. The postoperative
      course was good, and there was no paraplegia or other complications. A
      postoperative computed tomography scan demonstrated complete thrombosis of the
      descending thoracic aneurysm without endoleak. In conclusion, the frozen elephant
      trunk was effective as a one-stage operation for mega-aorta.

PMID- 21724659
TI  - Highly flexible nitinol mesh to encase aortocoronary saphenous vein grafts: first
      clinical experiences and angiographic results nine months postoperatively.
AB  - Saphenous vein graft patency is frequently limited by degeneration. Experimental
      studies have indicated that rigid external support of venous grafts by a
      flexible, tubular nitinol mesh may improve graft patency. The study presented was
      part of a prospective, randomized, multicenter first-in-man trial investigating
      the safety and effectiveness of nitinol-supported venous grafts in coronary
      artery bypass graft (CABG) surgery. From our clinic, 25 subjects with multivessel
      coronary artery disease requiring saphenous vein graft CABG of the right coronary
      artery (RCA) and the circumflex artery were entered into the trial. Subjects were
      randomized to receive a mesh-supported graft on one of these arteries; the other
      vessel received an untreated vein graft. Graft patency was assessed by coronary
      angiography nine months after surgery. The implantation of mesh grafts was simple
      and safe. In 10 cases, a nitinol mesh-supported venous graft was anastomosed to
      the circumflex artery and in 15 cases to the RCA. All patients survived the
      observation period. A total of 72% of the patients underwent control coronary
      angiography. The patency rate of mesh-supported grafts was 27.8% nine months
      postoperatively. Conventional vein grafts showed an 85.7% patency, and arterial
      grafts had a 100% patency. No complications directly related to the implantation
      of mesh-supported grafts were observed. The promising experimental results of
      mesh-supported venous grafts could not be reproduced in the study presented. A
      critical item seems to be correct selection of nitinol mesh diameter, the
      anastomotic method and fixation of the mesh tube to the venous graft.

PMID- 21724661
TI  - Protective effects of Asparagus racemosus on oxidative damage in isoniazid
      induced hepatotoxic rats: an in vivo study.
AB  - To investigate the hepatoprotective activity of Asparagus racemosus against
      isoniazid-induced hepatotoxicity in male albino rats. Rats (n = 6 per group)were
      divided into four groups: saline-treated control, saline-treated control with A.
      racemosus extract (50 mg/kg), isoniazid treatment alone (100 mg/kg,
      intraperitoneal [i.p.]), and isoniazid-A. racemosus extract (50
      mg/kg)administered orally as cotreatment. Animals were treated for 21 days and
      euthanized 1 h after the last drug administration. Evaluated body weight, serum
      levels of alanine aminotransferase, aspartate aminotransferase, alkaline
      phosphatase, g-glutamyl transferase, total protein, albumin, hepatic
      malondialdehyde content, superoxide dismutase, catalase, cytochrome P450 2E1
      (CYP2E1)activity and glutathione (GSH). A. racemosus extract prevented isoniazid
      induced hepatotoxicity, indicated by both diagnostic indicators of liver damage,
      liver functional profile, significantly (p < 0.05)inhibited CYP2E1 activity,
      markedly attenuated oxidative stress by improved enzymatic, non-enzymatic
      antioxidants levels and mitigate malondialdehyde, lipid hydroperoxide
      significantly (p < 0.05). These results suggest that A. racemosus extract exerts
      its hepatoprotective activity by inhibiting the production of free radicals and
      acts as a scavenger, reducing the free radical generation via inhibition of
      hepatic CYP2E1 activity, increasing the removal of free radicals through the
      induction of antioxidant enzymes and improving non-enzymatic thiol antioxidant
      GSH.

PMID- 21724662
TI  - Pulmonary rehabilitation in the United Kingdom.
AB  - We audited the UK provision of pulmonary rehabilitation (PR) for chronic
      obstructive pulmonary disease (COPD) and the quality of the programmes provided
      against national standards. All eligible UK Acute Trusts were invited to
      participate in a national audit of COPD in 2008. Eleven quality indicators for PR
      were derived from the National Institute for Health and Clinical Excellence
      (NICE) and the British Thoracic Society guidelines. Participants provided details
      of staff involved in their programme to self-assess whether they met each quality
      indicator in full, partially or not at all. Data were collected using a bespoke
      Web tool. Data were received from 239 acute units, a trust participation rate of
      98%. Of the 239 units, 138 (58%) had provision of PR for all eligible patients
      and 76 (32%) for some but not all patients. Of these 214 PR, 13 (6%) programmes
      met all 11 quality indicators in full, median 8 with an interquartile range (IQR)
      of 7-9 for all PR programmes. One third of the programmes fully met the standards
      that continuation PR phases be provided, staff be trained in resuscitation and
      services be fully audited. Despite widespread provision of PR in the UK, the
      quality of programmes is variable and often less than satisfactory. Lack of
      funding is cited as a primary barrier to all eligible COPD patients not receiving
      PR. Those responsible for PR must act to improve the quality of services and
      audit their effectiveness before service expansion to meet future demand that can
      be justified.

PMID- 21724663
TI  - Tannic acid mitigates cisplatin-induced nephrotoxicity in mice.
AB  - Cisplatin (CP) is a well-known chemotherapeutic drug that displays dose-limiting
      nephrotoxicity. In this study, tannic acid (TA), a naturally occurring plant
      polyphenol, was evaluated for its antioxidant and antigenotoxicity potential
      against the CP-induced renal oxidative stress and genotoxicity in Swiss albino
      mice. The mice were given a prophylactic treatment of TA orally at a dose of 40
      and 80 mg/kg body weight (b wt) for 7 consecutive days before the administration
      of a single intraperitoneal (i.p.) injection of CP at 7 mg/kg b wt. The
      modulatory effects of TA on CP-induced nephrotoxicity and genotoxicity were
      investigated by assaying oxidative stress biomarkers, serum kidney toxicity
      markers, DNA fragmentation, alkaline unwinding, micronuclei assay, and by
      histopathological examination of kidney architecture. CP administration altered
      the antioxidant levels, enhanced lipid peroxidation, induced DNA strand breaks,
      and altered the levels of micronuclei among polychromatic erythrocytes (PCEs)
      significantly (p < 0.001). Pretreatment of TA in mice showed significant (p <
      0.001) recovery in antioxidant status, viz., reduced glutathione content and its
      dependent enzymes, quinone reductase and gamma-glutamyl transpeptidase. TA
      significantly (p < 0.001) reinstated the normal serum levels of blood urea
      nitrogen (BUN) and creatinine. TA showed strongly inhibited (p < 0.001)
      micronuclei induction, DNA strand breaks, and DNA fragmentation. Thus, TA as a
      phytochemical protects kidneys through its antigenotoxic activity and antioxidant
      potential.

PMID- 21724664
TI  - Depressive symptoms, health behaviors, and subsequent inflammation in patients
      with coronary heart disease: prospective findings from the heart and soul study.
AB  - OBJECTIVE: Depression has been associated with inflammation in patients with
      coronary heart disease. However, it is uncertain whether depressive symptoms lead
      to inflammation or vice versa. METHOD: The authors evaluated 667 outpatients with
      established coronary heart disease from the Heart and Soul Study. Depressive
      symptoms were assessed annually with the 9-item Patient Health Questionnaire.
      Participants were categorized as having no significant depressive symptoms (score
      below 10 at all interviews), depressive symptoms (score of 10 or higher) at one
      interview, or depressive symptoms at two or more interviews. At baseline and 5
      year follow-up, fasting blood samples were collected to measure three
      inflammatory biomarkers: fibrinogen, interleukin-6 (IL-6), and high-sensitivity C
      reactive protein (hsCRP). RESULTS: Of the 667 participants, 443 had no depressive
      symptoms, 86 had depressive symptoms at one assessment, and 138 had depressive
      symptoms at two or more annual assessments. Across the three groups, greater
      depressive symptoms were associated with higher subsequent log-transformed levels
      of IL-6 and hsCRP, and the association with higher fibrinogen levels approached
      significance. Baseline inflammation did not predict subsequent depressive
      symptoms. The association of depressive symptoms with subsequent inflammation
      levels was eliminated after adjustment for health behaviors associated with
      depression-physical inactivity, smoking, and higher body mass index. CONCLUSIONS:
      Depressive symptoms predicted higher IL-6 and hsCRP levels among outpatients with
      coronary heart disease, but higher inflammation levels did not predict subsequent
      depressive symptoms. The association between depressive symptoms and inflammation
      was no longer significant after adjustment for health behaviors, which suggests
      these behaviors may mediate depressive effects.

PMID- 21724665
TI  - Design considerations for characterizing psychiatric trajectories across the
      lifespan: application to effects of APOE-epsilon4 on cerebral cortical thickness
      in Alzheimer's disease.
AB  - Characterization of developmental trajectories across the lifespan is integral to
      understanding the prodromal course of many neuropsychiatric illnesses and the
      significant risk factors for disease onset or unfavorable outcomes. However, the
      standard experimental designs used in psychiatric research are not ideal for this
      purpose. The authors review the limitations of the most commonly employed designs
      in studies that make developmental or lifespan inferences in psychiatry: cross
      sectional, single-cohort longitudinal, and unstructured multicohort longitudinal
      designs. Cross-sectional studies completely confound within- and between-subject
      sources of variation and hence rely on the presence of parallel trajectories and
      negligible sampling and age cohort differences for making valid developmental
      inferences. Delineating trajectories of within-individual change over substantial
      periods of time requires data covering long age spans that often cannot be
      covered using single-cohort longitudinal designs. Unstructured multicohort
      longitudinal designs are a commonly used alternative that can cover a longer age
      span in a shorter interval than necessary for a single-cohort design. However,
      the impact of cohort and sampling effects is often minimized or ignored in
      unstructured multicohort longitudinal designs. The authors propose that
      structured multicohort longitudinal designs are a particularly viable and
      underutilized class of designs in psychiatry that represents a significant
      improvement over cross-sectional designs and unstructured multicohort
      longitudinal designs for making developmental inferences while being more
      practical to implement than single-cohort longitudinal designs. As an example of
      this approach, the authors analyze changes in entorhinal cortex thickness in
      Alzheimer's disease in relation to APOE-epsilon4 genotype.

PMID- 21724667
TI  - Nitric oxide synthase genotype modulation of impulsivity and ventral striatal
      activity in adult ADHD patients and healthy comparison subjects.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a highly heritable
      disorder. The NOS1 gene encoding nitric oxide synthase is a candidate gene for
      ADHD and has been previously linked with impulsivity. In the present study, the
      authors investigated the effect of a functional variable number of tandem repeats
      (VNTR) polymorphism in NOS1 (NOS1 exon 1f-VNTR) on the processing of rewards, one
      of the cognitive deficits in ADHD. METHOD: A sample of 136 participants,
      consisting of 87 adult ADHD patients and 49 healthy comparison subjects,
      completed a reward-related impulsivity task. A total of 104 participants also
      underwent functional magnetic resonance imaging during a reward anticipation
      task. The effect of the NOS1 exon 1f-VNTR genotype on reward-related impulsivity
      and reward-related ventral striatal activity was examined. RESULTS: ADHD patients
      had higher impulsivity scores and lower ventral striatal activity than healthy
      comparison subjects. The association between the short allele and increased
      impulsivity was confirmed. However, independent of disease status, homozygous
      carriers of the short allele of NOS1, the ADHD risk genotype, demonstrated higher
      ventral striatal activity than carriers of the other NOS1 VNTR genotypes.
      CONCLUSIONS: The authors suggest that the NOS1 genotype influences impulsivity
      and its relation with ADHD is mediated through effects on this behavioral trait.
      Increased ventral striatal activity related to NOS1 may be compensatory for
      effects in other brain regions.

PMID- 21724666
TI  - Exaggerated activation of dorsal anterior cingulate cortex during cognitive
      interference: a monozygotic twin study of posttraumatic stress disorder.
AB  - OBJECTIVE: Neuroimaging studies have revealed functional abnormalities in the
      anterior cingulate cortex in posttraumatic stress disorder (PTSD). The goal of
      this study was to determine whether hyperresponsivity of the dorsal anterior
      cingulate in PTSD is an acquired characteristic or a familial risk factor.
      METHOD: Using a case-control twin design, the authors studied combat-exposed
      veterans with PTSD (N=12) and their identical combat-unexposed co-twins (N=12),
      as well as combat-exposed veterans without PTSD (N=14) and their identical combat
      unexposed co-twins (N=14). Participants underwent functional MRI during
      completion of the Multi-Source Interference Task, which reliably activates the
      dorsal anterior cingulate. RESULTS: Combat-exposed veterans with PTSD and their
      unexposed co-twins had significantly greater activation in the dorsal anterior
      cingulate and tended to have larger response time difference scores, as compared
      to combat-exposed veterans without PTSD and their co-twins. Dorsal anterior
      cingulate activation in the exposed twins was positively correlated with their
      PTSD symptom severity. Dorsal anterior cingulate activation in the unexposed
      twins was positively correlated with their combat-exposed co-twins' PTSD symptom
      severity, but not with depression or alcohol use severity in the combat-exposed
      co-twins. CONCLUSIONS: Hyperresponsivity in the dorsal anterior cingulate appears
      to be a familial risk factor for the development of PTSD following psychological
      trauma.

PMID- 21724668
TI  - When is polypharmacy an advantage?

PMID- 21724669
TI  - The search for improved antidepressant strategies: is bigger better?

PMID- 21724670
TI  - Antipsychotic polypharmacy: are two ever better than one?

PMID- 21724671
TI  - Adapting treatment to patient problems.

PMID- 21724672
TI  - Neuroscience, clinical evidence, and the future of psychiatric classification in
      DSM-5.

PMID- 21724673
TI  - Buprenorphine for prescription opioid addiction in a patient with depression and
      alcohol dependence.

PMID- 21724674
TI  - Paul Cezanne, 1839-1906.

PMID- 21724675
TI  - Anti-NMDA receptor encephalitis versus pediatric catatonia.

PMID- 21724676
TI  - Comment on the association of stigma with violence.

PMID- 21724677
TI  - Monitoring ketamine treatment response in a depressed patient via peripheral
      mammalian target of rapamycin activation.

PMID- 21724678
TI  - The Asclepius: the ancient standard of physicians.

PMID- 21724679
TI  - Modern management of malignant hypercalcemia.
AB  - Hypercalcemia occurs in 10% to 20% of those with advanced cancer. It is
      considered an oncologic emergency. Presenting symptoms include common
      gastrointestinal symptoms that may be difficult to differentiate from tumor or
      treatment-related symptoms. These include nausea, vomiting, and constipation. As
      levels increase or if development is rapid, neuropsychiatric symptoms such as
      delirium can develop. Untreated it will lead to coma and death. Current preferred
      therapies are the bisphosphonate agents, zoledronate and pamidronate with saline
      rehydration.

PMID- 21724680
TI  - Relation between thyroid-stimulating hormone and the occurrence of cardiovascular
      events and mortality in patients with manifest vascular diseases.
AB  - AIMS: To investigate whether levels of thyroid-stimulating hormone (TSH) within
      the normal range are associated with an increased risk of new vascular events and
      mortality in patients with clinical manifest vascular diseases and whether this
      relation is influenced by adiposity. METHODS AND RESULTS: Prospective cohort
      study in 2443 patients (1790 men and 653 women) with clinical manifest vascular
      disease and TSH levels in the normal range. Median follow up was 2.7
      (interquartile range 1.4-3.9) years. Clinical endpoints of interest were:
      myocardial infarction, stroke, vascular death, and all-cause mortality. In
      patients with manifest vascular disease, the prevalence of (subclinical)
      hypothyroidism was 5.7%, while 3.6% had (subclinical) hyperthyroidism. An
      increase in 1 unit of TSH was associated with a 33% higher risk (HR 1.33; 95% CI
      1.03-1.73) for the occurrence of myocardial infarction, adjusted for age, gender,
      renal function, and smoking. In patients with a body mass index (BMI) below the
      median of 26.7 kg/m(2) the HR per unit TSH for myocardial infarction was 1.55
      (95% CI 1.08-2.21) compared to 1.18 (95% CI 0.81-1.71) in patients with a BMI
      >=26.7 kg/m(2). Visceral adipose tissue thickness below the median (<=8.8 cm) was
      associated with higher HR per unit TSH for myocardial infarction (HR 1.69; 95% CI
      1.21-2.35) compared to visceral adipose tissue thickness >8.9 cm (HR 1.00; 95% CI
      0.66-1.49). There was no relation between TSH and risk of stroke, vascular death,
      the combined endpoint, or all-cause mortality. CONCLUSION: Higher TSH levels
      within the normal range are associated with an increased risk of myocardial
      infarction, in patients with clinical manifest vascular disease. This relation is
      most prominent in patients without visceral obesity.

PMID- 21724681
TI  - Effect of exercise training on vascular endothelial function in patients with
      stable coronary artery disease: a randomized controlled trial.
AB  - BACKGROUND: We aim to investigate the effect of exercise training on endothelial
      function and exercise capacity in patients with coronary artery disease. METHODS
      AND RESULTS: A randomized, controlled trial was conducted to determine the
      effects of an 8-week exercise training programme (n = 32) vs. controls (n = 32)
      on brachial flow-mediated dilation (FMD) in patients with stable CAD. After 8
      weeks, patients received exercise training had significant improvements in FMD
      (1.84%, p = 0.002) and exercise capacity (2.04 metabolic equivalents, p < 0.001)
      compared with controls. The change in FMD correlated inversely with baseline FMD
      (r = -0.41, p = 0.001) and positively with the increase in exercise capacity (r =
      0.35, p = 0.005). After adjusting for confounders, every 1 metabolic equivalent
      increase in exercise capacity was associated with 0.55% increase in FMD.
      Furthermore, patients received exercise training had significantly increased high
      density lipoprotein cholesterol and decreased diastolic blood pressure and
      resting heart rate compared with controls. However, exercise training did not
      alter high-sensitivity C-reactive protein, oxidative stress measured as
      superoxide dismutase and 8-isoprostane, and CD34/KDR + endothelial progenitor
      cell count. Subgroup analysis showed that FMD was significantly improved only in
      CAD patients with baseline low exercise capacity (<median value of 7.65 metabolic
      equivalents, p = 0.004) but not in those with normal exercise capacity.
      CONCLUSION: Exercise training improved FMD and exercise capacity in stable CAD
      patients independent of the changes in inflammation, oxidative stress, or
      endothelial progenitor cells. The beneficial effects of exercise training on FMD
      and exercise capacity are inter-related, and more pronounced in those with
      baseline impaired exercise capacity.

PMID- 21724682
TI  - No gender differences in prognosis and preventive treatment in patients with AMI
      without significant stenoses.
AB  - OBJECTIVE: To investigate possible gender differences in patients with acute
      myocardial infarction (AMI) and without significant stenoses on coronary
      angiography (CAG) regarding prognosis and use of secondary preventive medication.
      DESIGN: Nationwide register-based cohort study. PATIENTS: By compiling data from
      Danish registries, we identified 20,800 patients hospitalized with AMI during
      2005-2007. We included the 834 women and 761 men without significant stenoses on
      CAG who were discharged and alive after 60 days. MAIN OUTCOME MEASURES: All-cause
      mortality, recurrent AMI, and redeeming a prescription for a lipid-lowering drug,
      beta-blocker, clopidogrel, or aspirin within 60 days of discharge. RESULTS:
      During follow-up, 97 women and 60 men died, resulting in a crude female/male
      hazard ratio (HR) of 1.51 (95% CI 1.09-2.08). After adjustment for age, time
      period, and comorbidity, the gender difference was attenuated (HR 1.22, 95% CI
      0.86-1.72). AMI recurrence was experienced by 28 women and 29 men with a
      female/male HR 0.88 (95% CI 0.52-1.48). After multivariable adjustment results
      were similar (HR 0.84, 95% CI 0.50-1.43). More women than men redeemed a
      prescription for lipid-lowering drugs with no differences in other medication. In
      the adjusted models lipid-lowering drugs, beta-blockers, clopidogrel, and aspirin
      were all redeemed equally with odds ratio (OR) 1.25 (95% CI 0.99-1.59), OR 1.10
      (95% CI 0.88-1.37), OR 1.09 (95% CI 0.88-1.34), and OR 1.13 (95% CI 0.90-1.42),
      respectively. CONCLUSION: Our study shows that in a population of patients with a
      first admission for AMI and no significant stenoses on CAG, women share the same
      prospects as men regarding long-term prognosis and the extent of secondary
      preventive medical treatment.

PMID- 21724683
TI  - Fatal necrotizing fasciitis following human bite of the forearm.

PMID- 21724684
TI  - Proximal interphalangeal joint arthroplasty with silicone implants (NeuFlex) by a
      lateral approach: a series of 51 cases.
AB  - The aim of this study is to assess outcomes of a lateral surgical approach for
      proximal interphalangeal joint arthroplasty with NeuFlex((r)) silicone implants
      for primary degenerative osteoarthritis. We reviewed 51 arthroplasties performed
      on 43 patients. The mean follow up period was 36 months (range 18-42). The
      average preoperative range of motion (ROM) was 38 degrees . The average
      postoperative ROM was 63 degrees . In 21/51 (41%) cases, there was an average
      axial deviation of 17 degrees  (range 10-30 degrees ). VAS and Quick DASH scores
      improved. In 5/51 (10%) cases, further surgery was required. Our lateral approach
      seems to be effective and minimally invasive, providing adequate exposure.
      Contralateral incision and contralateral ligament reinforcement should be
      performed, whenever necessary, to improve lateral stability.

PMID- 21724685
TI  - Do patients really do better after the Sauve-Kapandji procedure when compared to
      the Darrach procedure? A systematic review.

PMID- 21724686
TI  - Two millimetre biopsy punch: a painless and practical instrument for evacuation
      of subungual haematomas in adults and children.

PMID- 21724687
TI  - Salmonella typhimurium in the hip: look before a SLE patient leaps.
AB  - Salmonellosis is a common infection in systemic lupus erythematosus patients. The
      present study reports on two such cases of Salmonella typhimurium septic
      arthritis among the 102 patients seen during a four-year period.

PMID- 21724688
TI  - Comparative analysis of tuberculous and brucellar spondylodiscitis.
AB  - Our aim was to compare the clinical, radiological and prognostic features of
      spontaneous spondylodiscitis secondary to tuberculosis (TS) and brucellosis (BS).
      This prospective study involved 41 patients diagnosed with spondylodiscitis. Of
      these, 18 (43.1%) had BS and 23 (56.1%) had TS. The mean age of TS patients was
      52 +/- 13.43 years and older than BS patients (P < 0.001). A prolonged clinical
      course of the disease, constitutional symptoms, lymphocytosis, increased
      erythrocyte sedimentation rate (ESR), presence of posterior vertebrae lesions and
      psoas abscesses were significantly more frequent in the TS group. There are
      significant clinical, biological and radiological differences between TS and BS.
      These differences permit a presumptive aetiological diagnosis and orient the
      initial empirical medical treatment while awaiting a final microbiological
      diagnosis.

PMID- 21724689
TI  - Clinical manifestations of co-infection with malaria and leptospirosis.
AB  - Though both malaria and leptospirosis are frequent in the tropics, co-infections
      are under-recognized due to overlapping of clinical features. Here, we reviewed
      clinical manifestations of published co-infection along with our three cases. Out
      of a total of 18 patients, nine patients (50%) required ICU admission. Almost all
      patients had prodromal symptoms in the form of fever, headache and myalgia. Seven
      patients (37%) had altered sensorium, three patients (17%) had hypotension at
      admission, and 11 patients (61%) had acute kidney injury (AKI). Pulmonary
      manifestations in the form of pulmonary bleeding were present in four cases
      (22%). Three (17%) patients had acute lung injury/ acute respiratory distress
      syndrome. Almost 55% patients had DIC in the form of altered prothrombin time,
      activated partial thromboplastin time and low fibrinogen level. Four patients
      (22%) had subconjuctival suffusion, two of them had haematuria, while one
      presented with nasal bleeding. All patients had altered liver function tests. Of
      all the 18 patients, 17 (94%) survived, while one died.

PMID- 21724690
TI  - Clinical profile of children with kerosene aspiration.
AB  - Accidental aspiration of kerosene is a common problem among children in
      developing countries. This descriptive study involved the retrospective analysis
      of children admitted with kerosene aspiration in a tertiary care hospital in
      South India for a year. Kerosene aspiration contributed to 60.4% of poisoning
      cases. Boys aged less than three years and from a rural background formed a
      significant proportion. Tachypnoea, cough and crepitations were the predominant
      clinical findings. Male gender and malnutrition (weight for age <80%) were
      significantly associated with prolonged hospital stay.

PMID- 21724691
TI  - Scrub typhus presenting as acute abdomen.
AB  - Scrub typhus, a zoonosis, is a systemic febrile illness with diverse clinical
      manifestations. It may also present with signs and symptoms of acute abdomen. We
      present two serologically confirmed cases of scrub typhus presenting with acute
      abdomen that were managed conservatively with antibiotics.

PMID- 21724692
TI  - Primary renal hydatidosis with associated macroscopic hydatiduria--a computed
      tomography urography diagnosis with pathological confirmation.
AB  - Primary renal hydatid disease which involves any other organ is extremely rare.
      Cystic rupture into the pelvicalyceal system, causing hydatiduria, is
      pathognomonic of renal hydatidosis, although it is usually microscopic and is
      seen in only 10-20% of renal hydatidosis cases. Gross hydaturia is uncommon but
      is present in the case discussed below. We report an exceptionally rare case of
      primary renal hydatidosis associated with the rupture of the cyst into the
      pelvicalyceal system diagnosed primarily on the basis of computed tomography
      urography. The diagnosis was confirmed on a pathological and surgical basis.

PMID- 21724693
TI  - Restoring the seal of an anatomical face mask.
AB  - The face mask is a device to facilitate the delivery of gases from a breathing
      system to a patient by creating an airtight seal around the face. Of the many
      types of face masks available, the anatomical face mask is most commonly used for
      anaesthesia. With repeated usage, the seal of the anatomical face mask becomes
      flattened due to the loss of air in the cushion, leading to a poor fit on the
      patient's face. This results in air dilution during spontaneous respiration and
      inadequate gas exchange during controlled ventilation. A simple solution to
      restore this seal has been provided.

PMID- 21724695
TI  - Expression of APRIL in diffuse large B cell lymphomas from patients with systemic
      lupus erythematosus and rheumatoid arthritis.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE) have an increased risk of diffuse large B cell lymphoma
      (DLBCL). The cytokine A PRoliferating-Inducing Ligand (APRIL) is strongly
      expressed in DLBCL in the general population and is detected in high
      concentrations in sera from subgroups of patients with RA and SLE. To investigate
      a possible association between APRIL and DLBCL in RA and SLE, we examined APRIL
      expression in lymphoma biopsies from patients with RA and SLE and from DLBCL
      patients without inflammatory disease. METHODS: Lymphoma tissue from 95 RA, 12
      SLE, and 63 comparator DLBCL cases were stained with anti-APRIL antibodies
      (Aprily-2). The percentage of positively stained cells of the comparator cases
      were divided into quartiles (1-4, where 4 = most stained) and compared with the
      results for the RA and SLE lymphomas. APRIL expression was correlated to clinical
      variables. RESULTS: The odds ratio for high expression of APRIL (quartiles 3 and
      4) was elevated in the SLE DLBCL (OR 23.6, 95% CI 2.4-231.2), but not in the RA
      DLBCL (OR 0.8, 95% CI 0.3-2.0). RA patients in quartile 4 had higher cumulated RA
      disease activity than those in quartile 1 (p = 0.013). Epstein-Barr virus in the
      lymphoma tissue was associated with high APRIL expression (p = 0.009).
      CONCLUSION: The high expression of APRIL in DLBCL in SLE and in an RA subset
      might indicate an association between APRIL and lymphoma in these subsets of
      rheumatic diseases, but could also reflect a dysregulation of APRIL per se in
      these patient groups.

PMID- 21724696
TI  - Soluble receptor for advanced glycation endproducts is decreased in patients with
      juvenile idiopathic arthritis (ERA category) and inversely correlates with
      disease activity and S100A12 levels.
AB  - OBJECTIVE: Membrane-bound receptor for advanced glycation endproducts (mRAGE) is
      overexpressed in response to increasing concentrations of its ligand (e.g.,
      S100A12) and triggers an inflammatory immune response. In contrast, soluble RAGE
      (sRAGE) acts as a decoy receptor and downmodulates inflammation. Decreased sRAGE
      levels are associated with autoimmune diseases; however, limited data are
      available in juvenile idiopathic arthritis (JIA). We studied sRAGE levels in
      patients with JIA [enthesitis-related arthritis (ERA) category]. METHODS: sRAGE
      levels were estimated in the serum of patients with ERA JIA (n = 101), systemic
      onset JIA and polyarticular JIA (n = 10 each), and healthy controls (n = 45).
      Synovial fluid (SF) sRAGE was measured in patients with ERA, rheumatoid
      arthritis, reactive arthritis, and osteoarthritis (n = 10). Levels of S100A12
      were also measured. Twenty-four patients with ERA were followed for 4 months.
      Disease activity was assessed by swollen joint count (SJC), tender joint count
      (TJC), and erythrocyte sedimentation rate (ESR). All levels are expressed as
      median (range). RESULTS: The serum sRAGE (pg/ml) level was significantly lower in
      patients compared to healthy controls [515 (64-1887) vs 1542 (627-3159); p <
      0.0001]. In paired samples, SF had lower levels compared to corresponding plasma
      level [102 (51-799) vs 481 (134-1006); p < 0.0001]. The level of S100A12 (ng/ml)
      was higher in SF (1042; 573-1415) than serum (638; 208-779). Serum sRAGE
      correlated negatively with S100A12 levels (r = -0.474; p < 0.01.), ESR (r = 
      0.306; p < 0.01), and SJC (r = -0.237; p < 0.05), but not with TJC (r = -0.134; p
      = NS). The levels of sRAGE remained stable over time in patients with stable
      disease. CONCLUSION: Levels of sRAGE are reduced in patients with ERA and
      correlate negatively with disease activity and S100A12 levels. sRAGE may be a
      modulator of inflammation in these patients.

PMID- 21724697
TI  - High serum levels of CXCL11 in mixed cryoglobulinemia are associated with
      increased circulating levels of interferon-gamma.
AB  - OBJECTIVE: No study has evaluated circulating chemokine C-X-C motif ligand
      (CXCL)11 in patients with "mixed cryoglobulinemia and chronic hepatitis C
      infection" (MC+HCV). We measured CXCL11, and correlated this measurement to the
      clinical phenotype. METHODS: Serum CXCL11, interferon-gamma (IFN-gamma), and
      tumor necrosis factor-alpha (TNF-alpha) were assayed in 97 MC+HCV patients and in
      97 sex- and age-matched controls. RESULTS: MC+HCV patients showed significantly
      higher mean CXCL11 serum levels than controls (254 +/- 295, 68 +/- 16 pg/ml,
      respectively; p = 0.0002; ANOVA). CXCL11 was significantly increased in 36
      cryoglobulinemic patients with compared to those without active vasculitis (303
      +/- 208 vs 179 +/- 62 pg/ml, respectively; p < 0.001; ANOVA). IFN-gamma levels
      were significantly higher in MC+HCV than in controls [6.1 (range 0.8-114.5), 1.4
      (range 0.7-2.4) pg/ml, respectively; p < 0.05; Mann-Whitney U test]. Serum TNF
      alpha mean levels were significantly higher in MC+HCV than in controls [13.4
      (range 1.8-369), 1.1 (range 0.7-3.2) pg/ml, respectively; p < 0.0001; Mann
      Whitney U test]. A multiple regression analysis considering CXCL11 as a dependent
      variable, and age, alanine aminotransferase, IFN-gamma, and TNF-alpha as
      independent variables, showed in MC+HCV patients a significant association only
      with IFN-gamma (p < 0.0001). CONCLUSION: Our study demonstrates markedly high
      serum levels of CXCL11 in patients with MC+HCV compared to healthy controls
      overall in the presence of active vasculitis. A strong relationship between
      circulating IFN-gamma and CXCL11 was shown, strongly supporting the role of a T
      helper 1 immune response in the pathogenesis of MC+HCV.

PMID- 21724698
TI  - Nonsteroidal antiinflammatory drug withdrawal in patients with stable rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the effect of nonsteroidal antiinflammatory drug (NSAID)
      withdrawal on blood pressure (BP), 44-joint Disease Activity Score (DAS44), and
      functional assessments in patients with stable rheumatoid arthritis (RA).
      METHODS: NSAID was withdrawn from 30 patients with stable RA (DAS44 <= 2.8).
      Other prescribed medication continued. Clinical and laboratory measures were
      taken at baseline, 6 weeks, and 12 weeks. RESULTS: No participants required NSAID
      reintroduction during the study period. Significant improvement in systolic BP
      was noted: maximal median reduction was 7 mm Hg (baseline to 12 weeks). There was
      no significant deterioration in DAS44 or function. Eleven participants required
      additional intervention. CONCLUSION: NSAID withdrawal resulted in improvement in
      BP without loss of disease control.

PMID- 21724700
TI  - Is there an advantage over SF-36 with a quality of life measure that is specific
      to systemic lupus erythematosus?
AB  - OBJECTIVE: To assess whether the Lupus Quality of Life (LupusQoL) questionnaire
      contributed additional information not obtained using the Medical Outcomes Study
      Short-Form 36 questionnaire (SF-36) in a cohort of patients with systemic lupus
      erythematosus (SLE). METHODS: Forty-one patients seen at a single center were
      followed at monthly intervals for 12 months. The LupusQoL and the SF-36
      questionnaires were coadministered monthly. Disease activity was determined by
      the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) every 30
      days. We determined the correlation of the 4 comparable domains of both
      questionnaires. For the 4 noncomparable domains of the LupusQoL we determined the
      correlation between each domain with the Physical Component Summary scores (PCS)
      and the Mental Component Summary scores (MCS) of the SF-36. The effect size (ES)
      and the standardized response mean (SRM) were used to compare the responsiveness
      of both questionnaires when a clinically significant change in disease activity
      occurred as determined by SLEDAI-2K. RESULTS: Three hundred seventy-six patient
      visits were recorded. There was a strong correlation between comparable domains
      in both questionnaires. For the 4 noncomparable domains of the LupusQoL, there
      was a correlation with the MCS and PCS of SF-36. The mean scores for comparable
      domains in both questionnaires were similar. Both questionnaires displayed
      responsiveness, as determined by ES and SRM among patients who flared and
      improved, but not among patients in remission, when compared to the previous
      visit. CONCLUSION: LupusQoL and SF-36 were equivalent in assessing quality of
      life over time in this group of patients. Both questionnaires are responsive
      measures of quality of life in patients with SLE flares and improvement.

PMID- 21724699
TI  - Minimally important differences of the UCLA Scleroderma Clinical Trial Consortium
      Gastrointestinal Tract Instrument.
AB  - OBJECTIVE: To provide minimally important difference (MID) estimates for the UCLA
      Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT
      2.0) in a longitudinal observational cohort. METHODS: We administered the UCLA
      SCTC GIT 2.0 to 115 patients with systemic sclerosis (SSc) at 2 timepoints 6
      months apart. The UCLA SCTC GIT 2.0 has 7 multi-item scales: Reflux,
      Distension/Bloating, Diarrhea, Fecal Soilage, Constipation, Emotional Well-being,
      and Social Functioning and a total GIT score. All scales are scored from 0
      [better health-related quality of life (HRQOL)] to 3 (worse HRQOL) except the
      diarrhea and constipation scales (ranges 0-2 and 0-2.5, respectively). Patients
      also rated their overall and upper and lower GIT involvement during the second
      visit using a response scale with options "much better; somewhat better; almost
      the same; somewhat worse; or much worse." The minimally changed group was defined
      by those reporting they were somewhat better or somewhat worse compared to first
      visit. RESULTS: Study participants were 84% female and 81% white with a mean
      disease duration of 6.9 years. The MID estimates for improvement ranged from 0.07
      for the Social Functioning scale to 0.36 for the Emotional Well-being scale. For
      worsening, the MID estimates ranged from 0.06 for the Fecal Soilage scale to 0.21
      for the Social Functioning scale. CONCLUSION: We provide MID estimates for the
      UCLA SCTC GIT 2.0 scales. This information can aid in interpreting scale scores
      in future randomized controlled trials and observational studies.

PMID- 21724701
TI  - CCL20 stimulates proinflammatory mediator synthesis in human fibroblast-like
      synoviocytes through a MAP kinase-dependent process with transcriptional and
      posttranscriptional control.
AB  - OBJECTIVE: To compare levels of the chemokine CCL20 and its receptor CCR6 in
      donor, osteoarthritic (OA), and rheumatoid arthritis (RA) synovium; and to
      determine the molecular mechanism of cellular activation induced by
      chemokine/receptor ligation in human fibroblast-like synoviocytes (FLS). METHODS:
      Synovia and isolated FLS from donor, OA, and RA joints were analyzed for CCL20
      and CCR6 expression by RT-PCR and immunohistochemistry. The effect of CCL20 on
      cytokines and mediators of cartilage degradation was examined by PCR for mRNA
      expression levels and ELISA, and Western blotting for protein. CCL20-dependent
      transcriptional and posttranscriptional activation of target genes was monitored
      using reporter constructs and luciferase assays in transfected donor FLS.
      RESULTS: CCL20 and CCR6 proteins were abundantly expressed in RA synovial lining
      cells compared to donor or OA synovia as judged by immunohistochemistry. RT-PCR
      of synovial extracts confirmed the predominance of CCL20/CCR6 mRNA expression in
      RA synovium. CCL20 mRNA expression was low in donor FLS, but increased
      dramatically after stimulation with recombinant human (rh) interleukin 1beta (IL
      1beta). rhCCL20 increased mRNA and protein expression of COX-2, IL-1beta, tumor
      necrosis factor-alpha, IL-6, and the matrix-destructive metalloprotease MMP-3 in
      donor FLS cultures. High constitutive levels of IL-6 were released from RA
      synovia; CCL20-induced expression of IL-6 occurred through an NSAID/COXIB
      sensitive process. CCL20-induced expression of COX-2 was mediated by a
      PLCP1/PKCalpha/MEK1/2/ERK1/2-dependent pathway involving both transcriptional and
      posttranscriptional mechanisms. CONCLUSION: CCL20/CCR6 may play an important role
      in the pathogenesis of RA by assembling the molecular and cellular components
      orchestrating synovitis.

PMID- 21724702
TI  - The distribution of congenital anomalies within the VACTERL association among
      tumor necrosis factor antagonist-exposed pregnancies is similar to the general
      population.
AB  - OBJECTIVE: To compare the distribution of congenital anomalies within the VACTERL
      association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal,
      and limb abnormalities) between patients exposed to tumor necrosis factor-alpha
      (TNF-alpha) antagonist and the general population. METHODS: Analysis for
      comparison of proportional differences to a previous publication between anomaly
      subgroups, according to subgroup definitions of the European Surveillance of
      Congenital Anomalies (EUROCAT), a population-based database. RESULTS: Most
      EUROCAT subgroups belonging to the VACTERL association contained only one or 2
      records of TNF-alpha antagonist exposure, so comparison of proportions was
      imprecise. Only the category "limb abnormalities" showed a significantly higher
      proportion in the general population. CONCLUSION: The high number of congenital
      anomalies belonging to the VACTERL association from a report of pregnancies
      exposed to TNF-alpha antagonists could not be confirmed using a population-based
      congenital anomaly database.

PMID- 21724704
TI  - Validation of the UCLA Scleroderma Clinica Trial Gastrointestinal Tract
      Instrument version 2.0 for systemic sclerosis.
AB  - OBJECTIVE: The University of California at Los Angeles (UCLA) Scleroderma
      Clinical Trial Consortium GI Tract Instrument (UCLA SCTC GITI) was recently
      developed to measure gastrointestinal tract disease in systemic sclerosis (SSc).
      Our study assesses the internal consistency and validity of the instrument in a
      different population than was used in the original study. METHODS: A sample of
      113 consecutive patients with SSc from the Canadian Scleroderma Research Group
      (CSRG) Registry completed the UCLA SCTC GITI, a self-administered questionnaire
      with 7 scales and an overall score. Reliability was evaluated using Cronbach's
      alpha coefficient and validity was determined by testing multiple constructs.
      RESULTS: Our subjects were slightly older than the original cohort, and had less
      formal education and less diffuse cutaneous disease. The overall score of the
      instrument correlated well with the GI scale of the Health Assessment
      Questionnaire for the Spondyloarthropathies (GI-S-HAQ; r = 0.58, p < 0.001) and
      the total number of GI symptoms (r = 0.77, p < 0.001). Each subscale correlated
      well with the GI-S-HAQ. The individual scales and the overall score were able to
      differentiate between categorical groupings of the GI-S-HAQ. The scale scores
      differentiated well those patients with clinical involvement of the corresponding
      GI problem. Multiple linear regression adjusting for age, disease duration, sex,
      and ethnicity showed that the UCLA SCTC GITI had a significant association with
      both the physical component summary and the mental component summary of the
      Medical Outcomes Study Short-Form 36 questionnaire. CONCLUSION: Our study
      confirms that the UCLA SCTC GITI version 2.0 will be a useful tool for assessing
      the role of GI involvement in SSc, even in a population with substantially
      different characteristics than the subjects originally tested.

PMID- 21724703
TI  - Matrix Gla protein polymorphism, but not concentrations, is associated with
      radiographic hand osteoarthritis.
AB  - OBJECTIVE: Factors associated with mineralization and osteophyte formation in
      osteoarthritis (OA) are incompletely understood. Genetic polymorphisms of matrix
      Gla protein (MGP), a mineralization inhibitor, have been associated clinically
      with conditions of abnormal calcification. We therefore evaluated the
      relationship of MGP concentrations and polymorphisms at the MGP locus to hand OA.
      METHODS: Ours was an ancillary study to a 3-year randomized trial assessing the
      effect of vitamin K supplementation on vascular calcification and bone loss among
      community-dwelling elders. We studied participants who had serum MGP
      concentration measured and DNA genotyped for 3 MGP genetic polymorphisms
      (rs1800802, rs1800801, and rs4236), and who had hand radiographs. We evaluated
      the cross-sectional associations of serum MGP and the 3 MGP genetic
      polymorphisms, respectively, with radiographic hand OA using logistic regression
      with generalized estimating equations, adjusting for potential confounders.
      RESULTS: Radiographic hand OA in >= 1 joint was present in 71% of the 376
      participants (mean age 74 years, mean body mass index 28 kg/m(2), 59% women). No
      significant association between serum MGP concentrations and radiographic hand OA
      was found [adjusted OR 1.0 (ref), 1.40, 1.21, and 1.21 for quartiles 1-4,
      respectively]. Homozygosity of the rs1800802 minor allele was associated with
      0.56 times lower prevalence of hand OA compared with having >= 1 major allele at
      this locus (95% CI 0.32-0.99, p = 0.046). CONCLUSION: There may be an association
      between hand OA and genetic polymorphism at the MGP locus that is not reflected
      by total MGP serum concentrations. Further studies are warranted to replicate and
      elucidate potential mechanisms underlying these observed associations.

PMID- 21724706
TI  - Safety and efficacy of febuxostat treatment in subjects with gout and severe
      allopurinol adverse reactions.
AB  - OBJECTIVE: Allopurinol, a purine base analog inhibitor of xanthine oxidase (XO)
      activity, remains the standard for pharmacologic urate-lowering management of
      gout. Allopurinol is efficacious and safe in most patients, but intolerance is
      estimated to occur in up to 10% of treated patients. Severe or life-threatening
      allopurinol adverse reactions (AE) occur much less frequently, and include severe
      cutaneous allopurinol reactions, vasculitis, and/or a multisystem allopurinol
      hypersensitivity syndrome. During clinical development of febuxostat (FEB), a
      recently approved non-purine analog inhibitor of XO, subjects with severe
      allopurinol intolerance were excluded from randomized double-blind
      FEB/allopurinol comparative trials. METHODS: In this retrospective study, safety
      and urate-lowering efficacy of FEB was assessed in 13 successively encountered
      gout patients with prior documented severe allopurinol reactions. RESULTS: FEB
      was well tolerated in 12 of 13 patients, each of whom remains on treatment. One
      patient previously hospitalized with documented exfoliative erythroderma during
      allopurinol treatment, developed biopsy-confirmed cutaneous leukocytoclastic
      vasculitis. None of the other 12 patients treated with FEB showed rash, worsening
      hepatic function, blood cytopenia or eosinophilia. CONCLUSION: In 12 of our 13
      gout patients with previously documented severe allopurinol AE, FEB treatment was
      safe. However, the development of a hypersensitivity type cutaneous vasculitis
      (likely but not definitively FEB-related) early in treatment mandates caution,
      careful dose escalation, and close monitoring when FEB urate-lowering therapy of
      allopurinol-intolerant patients is considered.

PMID- 21724705
TI  - Efficacy and safety of CH-1504, a metabolically stable antifolate, in patients
      with active rheumatoid arthritis: results of a phase II multicenter randomized
      study.
AB  - OBJECTIVE: To investigate the potential efficacy, safety, and tolerability of
      daily use of CH-1504 in patients with active rheumatoid arthritis (RA). US
      National Institutes of Health database no. NCT00658047. METHODS: In our phase II
      randomized double-blind double-dummy study, patients naive to methotrexate (MTX;
      n = 201) and having moderate to severe RA received either CH-1504 (0.25 mg, 0.5
      mg, or 1.0 mg once-daily oral doses) or MTX (titrated to 20.0 mg once-weekly oral
      doses). All received weekly 10-mg folate supplementation. Efficacy and safety
      were assessed at 2, 4, 8, and 12 weeks, with a treatment-free followup at 16
      weeks. Safety and tolerability were assessed. Primary efficacy endpoint was
      proportion of patients achieving ACR20 response at Week 12. Secondary endpoints
      included difference from baseline in the 28-joint Disease Activity Score (DAS28)
      and individual components of the American College of Rheumatology (ACR) composite
      index. RESULTS: Demographic characteristics were similar in all treatment groups:
      mean age 54.3 +/- 11.4 years, female sex 87%, mean baseline DAS28 6.6 +/- 0.9. At
      Week 12, CH-1504 demonstrated comparable efficacy compared to MTX as measured by
      ACR20, DAS28, and ACR composite core-set measures, including tender and swollen
      joints. No dose-response relationship was observed. Adverse events across
      treatment groups were mild. Liver enzyme levels increased from baseline to Week
      16 in the MTX group, with qualitatively lesser increases in the CH-1504 groups.
      Two patients in the MTX group withdrew because of gastrointestinal-related
      adverse events. CH-1504 appeared safe and well tolerated at all dose levels.
      CONCLUSION: CH-1504 has comparable efficacy to MTX and is safe and well
      tolerated. Metabolically stable antifolates are a promising therapeutic option
      that warrants further study.

PMID- 21724707
TI  - Association of baseline knee bone size, cartilage volume, and body mass index
      with knee cartilage loss over time: a longitudinal study in younger or middle
      aged adults.
AB  - OBJECTIVE: To determine the association of knee bone size, cartilage volume, and
      body mass index (BMI) at baseline with knee cartilage loss over 2 years in
      younger or middle-aged adults. METHODS: A total of 324 subjects (mean age 45 yrs,
      range 26-61) were measured at baseline and about 2 years later. Knee cartilage
      volume and bone size were determined using T1-weighted fat-saturated magnetic
      resonance imaging. RESULTS: In multivariable analysis, baseline knee bone size
      was negatively associated with annual change in knee cartilage volume at medial
      and lateral tibial sites (beta = -0.62% to -0.47%/cm(2), all p < 0.001). The
      associations disappeared at medial tibial site after adjustment for baseline
      cartilage volume and became of borderline statistical significance at lateral
      tibial site after adjustment for both baseline cartilage volume and osteophytes
      (beta = -0.29, p = 0.059). Baseline knee cartilage volume was consistently and
      negatively associated with annual change in knee cartilage volume at all 3 medial
      tibial, lateral tibial, and patellar sites (beta = -4.41% to -1.37%/ml, all p <
      0.001). Baseline BMI was negatively associated with an annual change in knee
      cartilage volume, but only in subjects within the upper tertile of baseline
      cartilage volume, even after adjusting for cartilage defects (beta = -0.16% to 
      0.34%/kg/m(2), all p < 0.05). CONCLUSION: Our study suggests that both higher
      baseline tibial bone area and knee cartilage volume (most likely due to cartilage
      swelling) are associated with greater knee cartilage loss over 2 years. A higher
      BMI was associated with greater knee cartilage loss only in subjects with higher
      baseline cartilage volume.

PMID- 21724708
TI  - Plectranthus amboinicus attenuates inflammatory bone erosion in mice with
      collagen-induced arthritis by downregulation of RANKL-induced NFATc1 expression.
AB  - OBJECTIVE: Plectranthus amboinicus has been known to treat inflammatory diseases
      or swelling symptoms. We investigated whether P. amboinicus exhibited an
      inhibitory effect on osteoclastogenesis in vitro and inflammatory bone erosion in
      collagen-induced arthritis (CIA) mice, an animal model of rheumatoid arthritis.
      We attempted to identify the active component of P. amboinicus involved in
      regulation of osteoclastogenesis. METHODS: We treated M-CSF- and RANKL-stimulated
      murine bone marrow-derived macrophages (BMM) and RANKL-induced RAW264.7 cells
      with different concentrations of P. amboinicus or rosmarinic acid, a
      phytopolyphenol purified from P. amboinicus, to monitor osteoclast formation by
      TRAP staining. The mechanism of the inhibition was studied by biochemical
      analysis such as RT-PCR and immunoblotting. CIA mice were administered gavages of
      P. amboinicus (375 mg/kg) or placebo. Then clinical, histological, and
      biochemical measures were assessed to determine the effects of P. amboinicus on
      synovial inflammation and bone erosion by H&E staining of the inflamed joints and
      ELISA. RESULTS: Rosmarinic acid strongly inhibited RANKL-induced NF-kappaB
      activation and nuclear factor of activated T cells c1 (NFATc1) nuclear
      translocation in BMM, and also inhibited RANKL-induced formation of TRAP-positive
      multinucleated cells. A pit formation assay and the CIA animal model showed that
      P. amboinicus significantly inhibited the bone-resorbing activity of mature
      osteoclasts. CONCLUSION: We postulated that rosmarinic acid conferred the
      inhibitory activity on P. amboinicus for inhibition of osteoclastogenesis via
      downregulation of RANKL-induced NFATc1 expression. Our results indicated the
      possibility of P. amboinicus as a new remedy against inflammatory bone
      destruction.

PMID- 21724709
TI  - All that glitters is not gold--standardizing diagnosis in rheumatoid arthritis
      studies.

PMID- 21724710
TI  - Who's holding up the queue? Delay in treatment of rheumatoid arthritis.

PMID- 21724711
TI  - Rehabilitation for ankylosing spondylitis in the era of biologics: any room left
      for this treatment?

PMID- 21724712
TI  - Should clinicians start measuring flow mediated dilation response in patients
      with systemic lupus erythematosus?

PMID- 21724713
TI  - Fluorescence optical imaging of juvenile arthritis.

PMID- 21724714
TI  - OMERACT 10--International Consensus Conference on Outcome Measures in
      Rheumatology Clinical Trials.

PMID- 21724715
TI  - Patient-reported outcomes in chronic gout: a report from OMERACT 10.
AB  - OBJECTIVE: To summarize the endorsement of measures of patient-reported outcome
      (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology
      Meeting (OMERACT 10). METHODS: During the OMERACT 10 gout workshop, validation
      data were presented for key PRO domains including pain [pain by visual analog
      scale (VAS)], patient global (patient global VAS), activity limitation [Health
      Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific
      measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were
      presented on all 3 aspects of the OMERACT filters of truth, discrimination, and
      feasibility. One PRO, health-related quality of life measurement with the Medical
      Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9.
      RESULTS: One measure for each of the 3 PRO of pain, patient global, and activity
      limitation was endorsed by > 70% of the OMERACT delegates to have appropriate
      validation data. Specifically, pain measurement by VAS was endorsed by 85%,
      patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by
      71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns
      including low internal consistency and lack of familiarity with the measure. More
      validation studies are needed for this measure. CONCLUSION: With the endorsement
      of one measure each for pain, patient global, SF-36, and activity limitation, all
      4 PRO for chronic gout have been endorsed. Future validation studies are needed
      for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout
      will be the focus of the next validation exercise for the OMERACT gout group.

PMID- 21724716
TI  - Tophus measurement as an outcome measure for clinical trials of chronic gout:
      progress and research priorities.
AB  - Despite the recognition that tophus regression is an important outcome measure in
      clinical trials of chronic gout, there is no agreed upon method of tophus
      measurement. A number of methods have been used in clinical trials of chronic
      gout, from simple physical measurement techniques to more complex advanced
      imaging methods. This article summarizes methods of tophus measurement and
      discusses their properties. Physical measurement using Vernier calipers meets
      most aspects of the Outcome Measures in Rheumatology (OMERACT) filter. Rigorous
      testing of the complex methods, particularly with respect to reliability and
      sensitivity to change, is needed to determine the appropriate use of these
      methods. Further information is also required regarding which method of physical
      measurement is best for use in future clinical trials. The need to develop and
      test a patient-reported outcome measure of tophus burden is also highlighted.

PMID- 21724717
TI  - Serum urate in chronic gout--will it be the first validated soluble biomarker in
      rheumatology?
AB  - OBJECTIVE: To summarize evidence for and endorsement of serum urate (SU) as
      having fulfilled the OMERACT filter as a soluble biomarker in chronic gout at the
      2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). METHODS: Data were
      presented to support the use of SU as a soluble biomarker in chronic gout and
      specifically the ability to utilize it to predict future patient-reported
      outcomes. RESULTS: SU was accepted as having fulfilled the OMERACT filter by 78%
      of voters. However, consensus was not obtained regarding its use as a soluble
      biomarker in chronic gout. Although the majority of the criteria for a soluble
      biomarker were fulfilled, the key criterion of association of the biomarker with
      outcomes was not agreed upon. It was agreed that the appropriate choice of
      endpoint must be linked to its clinical importance to the individual with the
      disorder and its temporal relationship to the intervention. Appropriate outcomes
      in chronic gout may therefore include gout flares, reduction in tophi, and
      patient-reported outcomes. CONCLUSION: SU is a critical outcome measure. It has
      the potential to fulfil criteria for a soluble biomarker. Further analyses of
      existing data from randomized controlled trials will be required to determine
      whether SU can predict future important outcomes, in particular disability.

PMID- 21724718
TI  - Bringing it all together: a novel approach to the development of response
      criteria for chronic gout clinical trials.
AB  - OBJECTIVE: To review a novel approach for constructing composite response
      criteria for use in chronic gout clinical trials that implements a method of
      multicriteria decision-making. METHODS: Preliminary work with paper patient
      profiles led to a restricted set of core-set domains that were examined using
      1000MindsTM by rheumatologists with an interest in gout, and (separately) by
      OMERACT registrants prior to OMERACT 10. These results and the 1000Minds approach
      were discussed during OMERACT 10 to help guide next steps in developing composite
      response criteria. RESULTS: There were differences in how individual indicators
      of response were weighted between gout experts and OMERACT registrants. Gout
      experts placed more weight upon changes in uric acid levels, whereas OMERACT
      registrants placed more weight upon reducing flares. Discussion highlighted the
      need for a "pain" domain to be included, for "worsening" to be an additional
      level within each indicator, for a group process to determine the decision-making
      within a 1000Minds exercise, and for the value of patient involvement.
      CONCLUSION: Although there was not unanimous support for the 1000Minds approach
      to inform the construction of composite response criteria, there is sufficient
      interest to justify ongoing development of this methodology and its application
      to real clinical trial data.

PMID- 21724720
TI  - The OMERACT core set of outcome measures for use in clinical trials of ANCA
      associated vasculitis.
AB  - There has been a marked increase in the past 15 years in the number and quality
      of clinical trials in the idiopathic inflammatory vasculitides, especially the
      small-vessel vasculitides known as antineutrophil cytoplasmic autoantibody (ANCA)
      associated vasculitis [AAV; granulomatosis, with polyangiitis (Wegener's)]. These
      trials have been conducted by multicenter, international groups in Europe and the
      United States with financial support provided by government agencies and
      biopharmaceutical companies. This increased clinical trial activity in vasculitis
      has been accompanied by the development and validation of new outcome measures--a
      challenging process for these complex, multiorgan system diseases. The
      international OMERACT Vasculitis Working Group has developed and implemented an
      iterative research agenda that has utilized accumulated experience and datasets
      from several multicenter clinical trials and large cohort studies. This work has
      led to the development, evaluation, validation, and endorsement, through the
      OMERACT consensus and validation processes, of a "core set" of outcome
      measurements for use in clinical trials of AAV. The core set includes domains of
      disease activity, damage assessment, patient-reported outcomes, and mortality;
      there is at least one validated outcome measurement instrument available for each
      domain. This report reviews the domains of illness in AAV included in the OMERACT
      core set, describes the instruments validated to measure these domains, and
      presents the approved core set.

PMID- 21724719
TI  - Development of outcome measures for large-vessel vasculitis for use in clinical
      trials: opportunities, challenges, and research agenda.
AB  - Giant cell (GCA) and Takayasu's arteritis (TAK) are 2 forms of large-vessel
      vasculitis (LVV) that involve the aorta and its major branches. GCA has a
      predilection for the cranial branches, while TAK tends to affect the extracranial
      branches. Both disorders may also cause nonspecific constitutional symptoms.
      Although some clinical features are more common in one or the other disorder and
      the ages of initial presentation differ substantially, there is enough clinical
      and histopathologic overlap between these disorders that some investigators
      suggest GCA and TAK may be 2 processes within the spectrum of a single disease.
      There have been few randomized therapeutic trials completed in GCA, and none in
      TAK. The lack of therapeutic trials in LVV is only partially explained by the
      rarity of these diseases. It is likely that the lack of well validated outcome
      measures for LVV and uncertainties regarding trial design contribute to the
      paucity of trials for these diseases. An initiative to develop a core set of
      outcome measures for use in clinical trials of LVV was launched by the
      international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed
      by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative
      include: (1) to review the literature and existing data related to outcome
      assessments in LVV; (2) to obtain the opinion of experts and patients on disease
      content; and (3) to formulate a research agenda to facilitate a more data-based
      approach to outcomes development.

PMID- 21724722
TI  - Development of a disease severity and responder index for psoriatic arthritis
      (PsA)--report of the OMERACT 10 PsA special interest group.
AB  - Work within the Group for Research and Assessment of Psoriasis and Psoriatic
      Arthritis (GRAPPA) to develop and validate composite disease activity measures in
      PsA has progressed. At the Outcome Measures in Rheumatology Clinical Trials
      (OMERACT) 8 meeting, a core set of domains to be assessed in randomized
      controlled trials (RCT) and longitudinal observational studies (LOS) of PsA was
      agreed upon. At OMERACT 10, work to date regarding proposed composite responder
      indices was presented. Five proposed composite responder definitions for PsA were
      reviewed and discussed including new data from the GRACE (GRAppa Composite
      Exercise) study. There was agreement that the work to date was promising, and
      that developing composite outcome measures for use in RCT and LOS was important.
      Further work was required, including data on followup timepoints and less common
      phenotypes of PsA, to ensure that all subgroups were represented within GRACE.
      During discussion on the concept of composite measures for PsA, based on
      predominant/little/no involvement in several domains (such as skin versus joints,
      enthesitis, dactylitis, spondyloarthritis) it was acknowledged that a simple
      summative score encompassing all domains of PsA would be difficult to construct
      psychometrically and may not be appropriate. Ideally, any composite measure
      should retain the ability to differentiate between activity in individual
      domains, such as enthesitis or skin psoriasis, so that the influence of each can
      be assessed independently. Further work is required within the GRACE dataset to
      develop an optimal composite measure for PsA. Several proposals to date have
      shown preliminary validity according to the OMERACT filter.

PMID- 21724723
TI  - Endorsement of definitions of disease activity states and improvement scores for
      the Ankylosing Spondylitis Disease Activity Score: results from OMERACT 10.
AB  - The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite
      index to assess disease activity in ankylosing spondylitis (AS). Criteria for
      disease activity states and improvement scores are important for use in clinical
      practice, observational studies, and clinical trials, and have been proposed by
      the Assessment of SpondyloArthritis international Society (ASAS). At OMERACT 10,
      our aim was to obtain endorsement from OMERACT for the ASDAS disease activity
      states and response criteria proposed by the ASAS membership. This article
      summarizes the associated discussions, the scientific basis of the validation
      process, and the results from the voting sessions, and identifies areas for
      research using the ASDAS. OMERACT participants agreed with the selection of
      cutoff values, which now have the combined endorsement of ASAS and OMERACT and
      are ready to be used in clinical practice and in research settings.

PMID- 21724721
TI  - Toward development of a fibromyalgia responder index and disease activity score:
      OMERACT module update.
AB  - Following development of the core domain set for fibromyalgia (FM) in Outcome
      Measures in Rheumatology Clinical Trials (OMERACT) meetings 7 to 9, the FM
      working group has progressed toward the development of an FM responder index and
      a disease activity score based on these domains, utilizing outcome indices of
      these domains from archived randomized clinical trials in FM. Possible clinical
      domains that could be included in a responder index and disease activity score
      include pain, fatigue, sleep disturbance, cognitive dysfunction, mood
      disturbance, tenderness, stiffness, and functional impairment. Outcome measures
      for these domains demonstrate good to adequate psychometric properties, although
      measures of cognitive dysfunction need to be further developed. The approach used
      in the development of responder indices and disease activity scores for
      rheumatoid arthritis and ankylosing spondylitis represents heuristic models for
      our work, but FM is challenging in that there is no clear algorithm of treatment
      that defines disease activity based on treatment decisions, nor are there
      objective markers that define thresholds of severity or response to treatment.
      The process of developing candidate dichotomous responder definitions and
      continuous quantitative disease activity measures is described, along with
      participant discussions from OMERACT 10. Final results of this work will be
      published in a separate report pending completion of analyses.

PMID- 21724724
TI  - Early postoperative mortality following joint arthroplasty: a systematic review.
AB  - OBJECTIVE: To perform a systematic review of 30- and 90-day mortality rates in
      patients undergoing hip or knee arthroplasties. METHODS: Five databases were
      searched for English-language studies of mortality in hip or knee arthroplasties
      and the following data were extracted: patient characteristics (age, sex,
      ethnicity), arthroplasty characteristics (unilateral vs bilateral, hip vs knee),
      system factors (hospital volume and surgeon volume), year of study, etc.
      Mortality rates were compared across variable categories; proportions were
      compared using relative risk ratios and 95% confidence intervals. RESULTS: Out of
      650 titles and abstracts, 80 studies qualified for analysis. Of these, 35%, 34%,
      and 31% of studies provided 30-, 90-, and > 90-day mortality rates. Overall 30
      day mortality rates across all types of arthroplasties were 0.3%; 90-day, 0.7%.
      For those reports with specific rates, 30-day mortality was significantly higher
      in men than women [1.8% vs 0.4%, respectively; relative risk (RR) 3.93, 95% CI
      3.30-4.68] and in bilateral versus unilateral procedures (0.5% vs 0.3%; RR 1.6,
      95% CI 1.49-1.72), but no differences were noted by the underlying diagnosis of
      osteoarthritis (OA) versus rheumatoid arthritis (0.4% vs 0.3%; RR 0.77, 95% CI
      0.48-1.24). 90-day mortality showed nonsignificant trends favoring women, OA as
      the underlying diagnosis, and unilateral procedures. CONCLUSION: Several
      demographic and surgical factors were associated with higher 30-day mortality
      rates following knee and hip arthroplasties. More studies are needed to examine
      the effect of body mass index, comorbidities, and other modifiable factors, in
      order to identify interventions to lower mortality rates following arthroplasty
      procedures.

PMID- 21724725
TI  - Developing disease activity and response criteria in connective tissue disease
      related interstitial lung disease.
AB  - The interstitial lung diseases (ILD) are a group of heterogeneous diseases that
      exert significant morbidity and mortality in connective tissue diseases (CTD).
      There is no consensus on measures of disease activity or therapeutic
      responsiveness, which hampers effective drug development and regulatory
      evaluation of candidate therapies. The CTD-ILD Special Interest Group represents
      an international multidisciplinary effort to identify consensus on criteria to
      measure disease activity and therapeutic response in CTD-ILD. We summarize the
      design of the studies we are conducting and progress leading to the OMERACT 10
      and 2010 EULAR meetings.

PMID- 21724726
TI  - Where in the world is oral triamcinolone?

PMID- 21724727
TI  - Lupus related longitudinal myelitis.

PMID- 21724728
TI  - Who discovered the erythrocyte sedimentation rate?

PMID- 21724729
TI  - Coexistent Wegener's granulomatosis and Goodpasture's disease: what is the
      mechanism?

PMID- 21724730
TI  - Serum levels of HMGB1 in postmenopausal patients with rheumatoid arthritis:
      associations with proinflammatory cytokines, acute-phase reactants, and clinical
      disease characteristics.

PMID- 21724731
TI  - Acute presentation of tophaceous myelopathy.

PMID- 21724732
TI  - Positive cytoplasmic antineutrophil cytoplasmic antigen with PR3 specificity
      glomerulonephritis in a patient with subacute bacterial endocarditis.

PMID- 21724733
TI  - Ankylosing spondylitis refractory to tumor necrosis factor blockade responds to
      tocilizumab.

PMID- 21724734
TI  - Primary aldosteronism simulating polymyositis.

PMID- 21724735
TI  - Endothelial function after 10 days of bed rest in individuals at risk for type 2
      diabetes and cardiovascular disease.
AB  - Physical inactivity is considered to be deleterious to vascular health, and in
      particular in first-degree relatives to patients with type 2 diabetes (FDR) and
      persons born with low birth weight (LBW), who may later in life develop
      cardiovascular disease. A period of imposed physical inactivity could unmask this
      risk. We hypothesized that the impact of physical inactivity on endothelial
      function would be more marked in subjects at increased risk for type 2 diabetes
      and cardiovascular disease (LBW and FDR) compared with a matched control group
      (CON), all of whom were recruited via advertisements and via the Danish Birth
      Registry. Twenty LBW, 20 CON and 13 FDR were studied before and after 10 days of
      bed rest. Forearm blood flow (FBF) was measured by venous occlusion
      plethysmography during brachial intra-arterial infusion of acetylcholine or
      adenosine at baseline and with superimposed hyperinsulinaemia. Markers of
      endothelial activation and inflammation were measured in plasma. Bed rest did not
      change the vasodilator responses to adenosine or acetylcholine alone in any
      group, but reduced vasodilator responses to adenosine or acetylcholine during
      hyperinsulinaemia in LBW. Bed rest impaired insulin-mediated vasodilatation in
      CON and LBW and increased endothelial activation markers in FDR and LBW but not
      in CON. Vasodilator responses were very low in FDR prior to bed rest, and did not
      decrease further during bed rest. Physical inactivity does not impair endothelium
      dependent vasodilatation per se, but the vascular vasodilator effect of insulin
      diminished in CON and LBW after bed rest. In FDR, a further deterioration of FBF
      with inactivity is not possible.

PMID- 21724736
TI  - Ageing-dependent remodelling of ion channel and Ca2+ clock genes underlying sino
      atrial node pacemaking.
AB  - The function of the sino-atrial node (SAN), the pacemaker of the heart, is known
      to decline with age, resulting in pacemaker disease in the elderly. The aim of
      the study was to investigate the effects of ageing on the SAN by characterizing
      electrophysiological changes and determining whether changes in gene expression
      are involved. In young and old rats, SAN function was characterized in the
      anaesthetized animal, isolated heart and isolated right atrium using ECG and
      action potential recordings; gene expression was characterized using quantitative
      PCR. The SAN function declined with age as follows: the intrinsic heart rate
      declined by 18 +/- 3%; the corrected SAN recovery time increased by 43 +/- 13%;
      and the SAN action potential duration increased by 11 +/- 3% (at 75%
      repolarization). Gene expression in the SAN changed considerably with age, e.g.
      there was an age-dependent decrease in the Ca(2+) clock gene, RYR2, and changes
      in many ion channels (e.g. increases in Na(v)1.5, Na(v)beta1 and Ca(v)1.2 and
      decreases in K(v)1.5 and HCN1). In conclusion, with age, there are changes in the
      expression of ion channel and Ca(2+) clock genes in the SAN, and the changes may
      provide a partial explanation for the age-dependent decline in pacemaker
      function.

PMID- 21724737
TI  - Ventilatory equivalents for carbon dioxide and oxygen are measures of ventilatory
      efficiency and not of pulmonary gas exchange efficiency.

PMID- 21724738
TI  - Reply: To PMID 21724737.

PMID- 21724739
TI  - BT-Nurse: computer generation of natural language shift summaries from complex
      heterogeneous medical data.
AB  - The BT-Nurse system uses data-to-text technology to automatically generate a
      natural language nursing shift summary in a neonatal intensive care unit (NICU).
      The summary is solely based on data held in an electronic patient record system,
      no additional data-entry is required. BT-Nurse was tested for two months in the
      Royal Infirmary of Edinburgh NICU. Nurses were asked to rate the
      understandability, accuracy, and helpfulness of the computer-generated summaries;
      they were also asked for free-text comments about the summaries. The nurses found
      the majority of the summaries to be understandable, accurate, and helpful
      (p<0.001 for all measures). However, nurses also pointed out many deficiencies,
      especially with regard to extra content they wanted to see in the computer
      generated summaries. In conclusion, natural language NICU shift summaries can be
      automatically generated from an electronic patient record, but our proof-of
      concept software needs considerable additional development work before it can be
      deployed.

PMID- 21724741
TI  - A flexible framework for deriving assertions from electronic medical records.
AB  - OBJECTIVE: This paper describes natural-language-processing techniques for two
      tasks: identification of medical concepts in clinical text, and classification of
      assertions, which indicate the existence, absence, or uncertainty of a medical
      problem. Because so many resources are available for processing clinical texts,
      there is interest in developing a framework in which features derived from these
      resources can be optimally selected for the two tasks of interest. MATERIALS AND
      METHODS: The authors used two machine-learning (ML) classifiers: support vector
      machines (SVMs) and conditional random fields (CRFs). Because SVMs and CRFs can
      operate on a large set of features extracted from both clinical texts and
      external resources, the authors address the following research question: Which
      features need to be selected for obtaining optimal results? To this end, the
      authors devise feature-selection techniques which greatly reduce the amount of
      manual experimentation and improve performance. RESULTS: The authors evaluated
      their approaches on the 2010 i2b2/VA challenge data. Concept extraction achieves
      79.59 micro F-measure. Assertion classification achieves 93.94 micro F-measure.
      DISCUSSION: Approaching medical concept extraction and assertion classification
      through ML-based techniques has the advantage of easily adapting to new data sets
      and new medical informatics tasks. However, ML-based techniques perform best when
      optimal features are selected. By devising promising feature-selection
      techniques, the authors obtain results that outperform the current state of the
      art. CONCLUSION: This paper presents two ML-based approaches for processing
      language in the clinical texts evaluated in the 2010 i2b2/VA challenge. By using
      novel feature-selection methods, the techniques presented in this paper are
      unique among the i2b2 participants.

PMID- 21724740
TI  - Computerization of workflows, guidelines, and care pathways: a review of
      implementation challenges for process-oriented health information systems.
AB  - OBJECTIVE: There is a need to integrate the various theoretical frameworks and
      formalisms for modeling clinical guidelines, workflows, and pathways, in order to
      move beyond providing support for individual clinical decisions and toward the
      provision of process-oriented, patient-centered, health information systems
      (HIS). In this review, we analyze the challenges in developing process-oriented
      HIS that formally model guidelines, workflows, and care pathways. METHODS: A
      qualitative meta-synthesis was performed on studies published in English between
      1995 and 2010 that addressed the modeling process and reported the exposition of
      a new methodology, model, system implementation, or system architecture. Thematic
      analysis, principal component analysis (PCA) and data visualisation techniques
      were used to identify and cluster the underlying implementation 'challenge'
      themes. RESULTS: One hundred and eight relevant studies were selected for review.
      Twenty-five underlying 'challenge' themes were identified. These were clustered
      into 10 distinct groups, from which a conceptual model of the implementation
      process was developed. DISCUSSION AND CONCLUSION: We found that the development
      of systems supporting individual clinical decisions is evolving toward the
      implementation of adaptable care pathways on the semantic web, incorporating
      formal, clinical, and organizational ontologies, and the use of workflow
      management systems. These architectures now need to be implemented and evaluated
      on a wider scale within clinical settings.

PMID- 21724742
TI  - Prospective Outcomes of Injury Study: recruitment, and participant
      characteristics, health and disability status.
AB  - The Prospective Outcomes of Injury Study aims to identify predictors of
      disability following injury. Participants were selected from the entitlement
      claims register of New Zealand's no-fault compensation insurer, the Accident
      Compensation Corporation, and followed up by interview for 2 years. This report
      describes changes to intended Prospective Outcomes of Injury Study methods and
      key characteristics of the cohort, with an emphasis on general health and
      disability before injury and soon afterwards. There were 2856 injured
      participants in the first interview, which occurred 3.2 months (median) after
      injury. The recruitment period was extended to enable inclusion of sufficient
      Maori participants. At the first interview, most participants were experiencing
      worse health status and increased disability compared to before injury, despite
      less than one-third reporting admission to hospital because of their injury.
      Analysis of outcome predictors related to post-injury function, disability and
      return-to-work soon after injury and 1 year later is now under way.

PMID- 21724743
TI  - Neighbourhood street connectivity and injury in youth: a national study of built
      environments in Canada.
AB  - BACKGROUND: The influence of the built environment on health is of contemporary
      societal interest. The design of streets in neighbourhood settings may contribute
      positively to the health of populations through increased physical activity, but
      it may also have injury consequences. METHODS: We conducted a national cross
      sectional study to describe the injury experiences of 9021 students from 180
      Canadian schools that participated in the 2006 Health Behaviour in School-Aged
      Children survey. Street designs surrounding each school (5 km circular buffer)
      were estimated via geographic information systems for three established measures
      of connectivity (intersection density, average block length and connected node
      ratio). A composite scale of connectivity was derived using factor analysis.
      Multilevel logistic regression analyses were used to examine the associations
      between the composite connectivity measure and students' reports of physical
      activity injuries occurring in the street (street injuries). RESULTS: Students
      living in neighbourhoods with low versus high street connectivity reported
      possible increases in the occurrence of street injuries (OR, 1.38; 95% CI, 0.84
      to 2.26). This relationship was mainly attributable to the occurrence of bicycle
      injuries (52% of all street injuries; OR, 2.33; 95% CI, 1.28 to 4.25). The
      population attributable risk was 20% for street injuries potentially caused by
      living in an area with low connectivity. CONCLUSION: The design of streets, as a
      measure of the built environment, is related to the occurrence of youth injury.
      Positive effects of poorly connected street designs that are likely in terms of
      physical activity were offset by negative injury outcomes, although the injuries
      observed were mostly minor in nature.

PMID- 21724744
TI  - Tobacco industry co-optation of culture? Converging culturally specific and
      mainstream tobacco products in India.

PMID- 21724745
TI  - Prospective epidemiological registers: a valuable tool for uncovering ALS
      pathogenesis.

PMID- 21724746
TI  - CT screening for lung cancer in the UK: position statement by UKLS investigators
      following the NLST report.
AB  - BACKGROUND: The imminent publication of a randomised controlled trial from the
      USA that suggests CT screening reduces mortality from lung cancer by more than
      20%, may potentially lead to one of the most important developments in lung
      cancer care. However, there remain important questions about the applicability of
      the results to the UK and the clinical effectiveness of this intervention,
      including its feasibility and cost-effectiveness. OBJECTIVE: To describe the
      remaining questions that need to be answered by further research and to comment
      on the use of CT screening in the UK outside a clinical trial. METHODS: The
      detailed design process of the UKLS protocol and international discussions were
      used to identify the research questions that remain to be answered and to inform
      those who may choose to consider offering CT screening, before these questions
      are answered. RESULTS: A series of research imperatives have been identified and
      we advise that CT screening should be part of the ongoing clinical trial in the
      UK, currently in the pilot phase (UKLS). UKLS is randomising 4,000 individuals
      for the pilot and a total of 32,000 for the main study. CONCLUSION: There remain
      unresolved issues with respect to CT screening for lung cancer. These include its
      feasibility, psychosocial and cost-effectiveness in the UK, harmonisation of CT
      acquisition techniques, management of suspicious screening findings, the choice
      of screening frequency and the selection of an appropriate risk group for the
      intervention. UKLS is aimed at resolving these issues.

PMID- 21724747
TI  - Do asbestos-related pleural plaques on HRCT scans cause restrictive impairment in
      the absence of pulmonary fibrosis?
AB  - BACKGROUND: It is uncertain whether isolated pleural plaques cause functional
      impairment. OBJECTIVE: To analyse the relationship between isolated pleural
      plaques confirmed by CT scanning and lung function in subjects with occupational
      exposure to asbestos. METHODS: The study population consisted of 2743 subjects
      presenting with no parenchymal interstitial abnormalities on the high-resolution
      CT (HRCT) scan. Asbestos exposure was evaluated by calculation of an individual
      cumulative exposure index (CEI). Each subject underwent pulmonary function tests
      (PFTs) and HRCT scanning. Variables were adjusted for age, smoking status, body
      mass index, CEI to asbestos and the centres in which the pulmonary function tests
      were conducted. RESULTS: All functional parameters studied were within normal
      limits for subjects presenting with isolated pleural plaques and for those
      presenting with no pleuropulmonary abnormalities. However, isolated parietal
      and/or diaphragmatic pleural plaques were associated with a significant decrease
      in total lung capacity (TLC) (98.1% predicted in subjects with pleural plaques
      vs. 101.2% in subjects free of plaques, p=0.0494), forced vital capacity (FVC)
      (96.6% vs. 100.4%, p<0.001) and forced expiratory volume in 1 s (FEV(1)) (97.9%
      vs. 101.9%, p=0.0032). In contrast, no significant relationship was observed
      between pleural plaques and FEV1/FVC ratio, forced expiratory flow at 25-75% FVC
      and residual volume. A significant correlation was found between the extent of
      pleural plaques and the reduction in FVC and TLC, whereas plaque thickness was
      not related to functional impairment. CONCLUSIONS: The results show a
      relationship between isolated parietal and/or diaphragmatic pleural plaques and a
      trend towards a restrictive pattern, although the observed decrease in FVC and
      TLC is unlikely to be of real clinical relevance for the majority of subjects in
      this series.

PMID- 21724749
TI  - Spatial orientation of the subtalar joint axis is different in subjects with and
      without Achilles tendon disorders.
AB  - BACKGROUND: There are many possible predisposing factors for Achilles tendon
      disorders suggested in the literature but their pathogenetic relevance is not
      proven in most cases. The asymmetric mechanical load distribution within the
      Achilles tendon during locomotion is frequently addressed as a major risk factor
      for Achilles tendon disorders. The spatial orientation of the subtalar joint axis
      (STA) may influence the Achilles tendon loading possibly leading to overload
      injuries. Hypothesis There is a significant difference between the orientation of
      the STA in subjects with and without Achilles tendon pathologies. MATERIALS AND
      METHODS: 614 subtalar joint axes determined in 307 long-distance runners with and
      without Achilles tendon disorders were included. Achilles tendon disorders were
      defined as any Achilles tendon-related pain during or following running, existing
      for more than 2 weeks in the past. Motion analysis of the foot was performed
      using an ultrasonic pulse-echo-based measurement system. The orientation of the
      STA was expressed by two angles. RESULTS: The mean inclination angle was 42 +/-
      16 degrees  and the mean deviation angle was 11 +/- 2 3 degrees . There was a
      significant difference (p=0.002) between the mean deviation angle measured in
      subjects with Achilles tendon pathologies (18 +/- 23 degrees ) and those without
      (10 +/- 23 degrees ). CONCLUSIONS: The results demonstrate a wide interindividual
      variability of the spatial orientation of the STA. In addition, the mean
      deviation angle in people with Achilles tendon pathologies is significantly more
      oblique than in people without. This finding indicates that the spatial
      orientation of the STA is related to the incidence of overuse injuries of the
      Achilles tendon in the investigated sample.

PMID- 21724748
TI  - Is age-related decline in lean mass and physical function accelerated by
      obstructive lung disease or smoking?
AB  - BACKGROUND: and aims Cross-sectional studies suggest that obstructive lung
      disease (OLD) and smoking affect lean mass and mobility. A study was undertaken
      to investigate whether OLD and smoking accelerate the ageing-related decline in
      lean mass and physical functioning. METHODS: 260 patients with OLD (mean+/-SD
      forced expiratory volume in 1 s (FEV1) 63+/-18% predicted), 157 smoking controls
      (FEV(1) 95+/-16% predicted), 866 former-smoking controls (FEV1 100+/-16%
      predicted) and 891 never-smoking controls (FEV1 104+/-17% predicted)
      participating in the Health, Aging and Body Composition (ABC) Study were studied.
      At baseline the mean age was 74+/-3 years and participants reported no functional
      limitations. Baseline and 7-year longitudinal data of body composition (by dual
      energy x-ray absorptiometry), muscle strength (by hand and leg dynamometry) and
      Short Physical Performance Battery (SPPB) were investigated. RESULTS: Compared
      with never-smoking controls, patients with OLD and smoking controls had a
      significantly lower weight, fat mass, lean mass and bone mineral content (BMC) at
      baseline (p<0.05). While the loss of weight, fat mass, lean mass and strength was
      comparable between patients with OLD and never-smoking controls, the SPPB
      declined 0.12 points/year faster in men with OLD (p=0.01) and BMC declined 4
      g/year faster in women with OLD (p=0.02). In smoking controls only lean mass
      declined 0.1 kg/year faster in women (p=0.03) and BMC 8 g/year faster in men
      (p=0.02) compared with never-smoking controls. CONCLUSIONS: Initially well
      functioning older adults with mild-to-moderate OLD and smokers without OLD have a
      comparable compromised baseline profile of body composition and physical
      functioning, while 7-year longitudinal trajectories are to a large extent
      comparable to those observed in never-smokers without OLD. This suggests a common
      insult earlier in life related to smoking.

PMID- 21724751
TI  - Phosphorus focus editorial.

PMID- 21724752
TI  - Novel role of androgens in mitochondrial fission and apoptosis.
AB  - Androgen and androgen receptors (AR) play critical roles in the proliferation of
      prostate cancer through transcriptional regulation of target genes. Here, we
      found that androgens upregulated the expression of dynamin-related protein 1
      (Drp1), which is involved in the induction of mitochondrial fission, a common
      event in mitosis and apoptosis. Clinical tissue samples and various prostate
      cancer cell lines revealed a positive correlation between Drp1 and AR levels.
      Treatment of androgen-sensitive cells with an AR agonist, R1881, and antagonist,
      bicalutamide, showed that Drp1 is transcriptionally regulated by androgens, as
      confirmed by an AR ChIP-seq assay. Live imaging experiments using pAcGFP1-Mito
      stably transfected LNCaP (mito-green) cells revealed that androgen did not induce
      significant mitochondrial fission by itself, although Drp1 was upregulated.
      However, when treated with CGP37157 (CGP), an inhibitor of mitochondrial Ca2+
      efflux, these cells exhibited mitochondrial fission, which was further enhanced
      by pretreatment with R1881, suggesting that androgen-induced Drp1 expression
      facilitated CGP-induced mitochondrial fission. This enhanced mitochondrial
      fission was correlated with increased apoptosis. Transfection with dominant
      negative (DN-Drp1, K38A) rescued cells from increased apoptosis, confirming the
      role of androgen-induced Drp1 in the observed apoptosis with combination
      treatment. Furthermore, we found that CGP reduced the expression of Mfn1, a
      protein that promotes mitochondrial fusion, a process which opposes fission. We
      suggest that androgen-increased Drp1 enhanced mitochondrial fission leading to
      apoptosis. The present study shows a novel role for androgens in the regulation
      of mitochondrial morphology that could potentially be utilized in prostate cancer
      therapy.

PMID- 21724753
TI  - Thromboelastographic changes after gonadectomy in retired racing greyhounds.
AB  - Twenty-one healthy greyhounds with no history or clinical signs of bleeding
      disorders, and no abnormalities on physical examination, complete blood count,
      serum biochemistry profiles (in dogs more than five years of age), and SNAP-4DX
      test for vector borne diseases underwent routine gonadectomies at the Ohio State
      University Veterinary Teaching Hospital. Blood samples were collected 24 hours
      before and after surgery by jugular venepuncture for thromboelastography and
      haemostasis assays (prothrombin time [PT], activated partial thromboplastin time
      [aPTT], fibrinogen concentration). The magnitude of the bleeding in each patient
      was estimated using a bleeding scoring system recently validated in greyhounds.
      Eight dogs were classified as bleeders and 13 as non-bleeders. Thromboelastograph
      (TEG) tracings in bleeders were different to that of non-bleeders. Neither sex
      (odds ratio [OR]: 0.148, P=0.05), haematocrit (OR: 0.907, P=0.39), platelet count
      (OR: 0.996, P=0.65) or age (OR: 0.949, P=0.83) were predictors of the outcome.
      None of the variables that evaluated clot kinetics, and fibrinolysis (that is,
      aPTT OR: 0.781, P=0.51; PT OR: 1.337, P=0.63; TEG(R) OR: 1.269, P=0.06; TEG(K)
      OR: 1.696, P=0.05; TEG(LY60) OR: 1.028, P=0.81) were able to predict the bleeding
      episodes. Only the TEG variables that represent the fibrin cross-linking of the
      clot (TEG(angle) OR: 0.903, P=0.03); and the strength of the clot (TEG(MA) OR:
      0.833, P=0.03) were considered predictors of the outcome.

PMID- 21724756
TI  - MPs' support for ban on wild animals in circuses.

PMID- 21724754
TI  - Rinderpest officially eradicated.

PMID- 21724757
TI  - Review panel to consider the future delivery of food standards in Scotland.

PMID- 21724758
TI  - Risk of EIA for UK horses travelling to endemic areas.

PMID- 21724760
TI  - FVE urged to support continued controls on E multilocularis.

PMID- 21724761
TI  - Veterinary medicines: product update.

PMID- 21724764
TI  - Rinderpest eradicated; what next?

PMID- 21724765
TI  - Peste des petits ruminants: a suitable candidate for eradication?
AB  - This year will see the final announcement, accompanied by much justifiable
      celebration, of the eradication from the wild of rinderpest, the 'cattle plague'
      that has been with us for so many centuries. The only known rinderpest virus
      (RPV) remaining is in a relatively small number of laboratories around the world,
      and in the stockpiles of vaccine held on a precautionary basis. As we mark this
      achievement, only the second virus ever eradicated through human intervention, it
      seems a good time to look at rinderpest's less famous cousin, peste des petits
      ruminants ('the plague of small ruminants') and assess if it should, and could,
      also be targeted for global eradication.

PMID- 21724766
TI  - Student and graduate support.

PMID- 21724767
TI  - Enhancing food production and public health.

PMID- 21724768
TI  - Use and misuse of antimicrobials.

PMID- 21724769
TI  - Survey of awareness of chicken parasites.

PMID- 21724770
TI  - Conception rates in dairy herds in the UK.

PMID- 21724771
TI  - A logo to reflect the profession?

PMID- 21724778
TI  - Promoting evidence-based and measurement-based care.

PMID- 21724779
TI  - Best practices: A national mental health learning collaborative on supported
      employment.
AB  - This column describes a best practice for dissemination and implementation used
      by the Johnson & Johnson-Dartmouth Program: a national learning collaborative
      among community mental health programs on supported employment. In this two
      tiered learning collaborative, researchers meet regularly with mental health and
      vocational rehabilitation leaders in 12 states and the District of Columbia, and
      state leaders oversee more than 130 individual programs in their respective
      states. Participants share educational programs, implementation and intervention
      strategies, practice experiences, outcome data, and research projects. The
      national learning collaborative facilitates implementation, dissemination,
      standardization, and sustainability of supported employment.

PMID- 21724780
TI  - Law & psychiatry: Murder, inheritance, and mental illness.
AB  - Should a murderer be allowed to inherit the victim's estate? The question dates
      from biblical times, but most jurisdictions today have statutes in place that bar
      inheritance by convicted murderers. However, a special problem arises when the
      killer has a severe mental illness and has been found not guilty by reason of
      insanity. Should such people, who have not been convicted of a crime, be
      permitted to collect their inheritance? Jurisdictions vary in their responses,
      with the rules reflecting a mix of practical and moral considerations influenced
      by different perspectives about what determines the behavior of persons with
      mental illness.

PMID- 21724781
TI  - Economic grand rounds: Income inequality and depression prevalence across the
      United States: an ecological study.
AB  - Research has shown a relationship between income inequality and poor health. This
      column reports findings from a state-level study of the relationship between
      income inequality and the prevalence of depression. Estimates of depression
      prevalence by state, obtained from the Behavioral Risk Factor Surveillance
      System, were linked with Gini coefficients for U.S. household income, obtained
      from the Census Bureau. The current prevalence of depression was significantly
      associated with income inequality--the more unequal, the higher the depression
      prevalence. The association persisted after adjustment for income per capita,
      percentage of the population with a college degree, and percentage over age 65
      years.

PMID- 21724782
TI  - Randomized trial of critical time intervention to prevent homelessness after
      hospital discharge.
AB  - OBJECTIVE: This study assessed the effectiveness of a previously tested model,
      critical time intervention (CTI), in producing an enduring reduction in the risk
      of homelessness for persons with severe mental illness who were discharged from
      inpatient psychiatric treatment facilities. METHODS: A total of 150 previously
      homeless men and women with severe mental illness and who were discharged from
      inpatient psychiatric hospitalization to transitional residences on the hospital
      grounds were randomly assigned to receive usual care or usual care plus CTI at
      the point of discharge to the community. The nine-month intervention aims to
      gradually pass responsibility to community sources for providing ongoing support
      after the intervention ends, thereby leading to a durable reduction in risk of
      future homelessness. After participants were discharged from the transitional
      residence (length of stay six to 937 days), their housing status was assessed
      every six weeks for 18 months via participant self-report collected by
      interviewers blind to study condition. RESULTS: In an intent-to-treat analysis,
      participants assigned to the CTI group had significantly less homelessness at the
      end of the follow-up period (the final three six-week intervals) than those
      assigned to the control group (odds ratio=.22, 95% confidence interval=.06-.88).
      CONCLUSIONS: A relatively brief, focused intervention for persons with severe
      mental illness led to a reduction in the risk of homelessness that was evident
      nine months after the intervention ended. This work suggests that targeted,
      relatively short interventions applied at critical transition points may enhance
      the efficacy of long-term supports for persons with severe mental illness who are
      living in the community.

PMID- 21724783
TI  - Overuse of antidepressants in a nationally representative adult patient
      population in 2005.
AB  - OBJECTIVE: Concerns have been raised that antidepressants may be overused. This
      study aimed to provide an estimate of antidepressant overuse in a more recent,
      nationally representative sample of adults and with a more contemporary set of
      antidepressants than has been covered in prior studies. METHODS: The data set
      included adult (weighted N=23,026,608) respondents who self-reported
      antidepressant treatment in the household and prescription drug components of the
      2005 Medical Expenditure Panel Survey. Overuse was defined as off-label
      antidepressant prescribing with limited or no scientific support for use as a
      treatment for the diagnosis, according to the Physicians' Desk Reference, the
      United States Pharmacopeia-National Formulary, and the Micromedex DrugDx data
      system. Stratification and multivariate logistic regression was used to examine
      clinical and socioeconomic predictors of overuse. RESULTS: Overuse was estimated
      at 20%, with the majority concentrated in newer-generation antidepressants (74%
      of overuse). Another 30%-40% of overuse was associated with documented diagnoses
      that may represent a reasonable clinical rationale for antidepressant use or
      suggest underdiagnosis of possible depressive and anxiety syndromes. Older age
      (odds ratio [OR]=.95, p=.03) and self-report of poor mental health (OR=.80,
      p=.02) were negatively associated with overuse. CONCLUSIONS: Antidepressant
      overuse among adults is less common than previously reported. Our results suggest
      that the actual extent of overuse may be lower than 20%. To improve treatment
      quality and the efficiency of the U.S. health care system, nationally
      representative data collection efforts on prescription drug use should aim to
      include enhanced measures of need in order to further refine future estimates of
      antidepressant overuse.

PMID- 21724784
TI  - National trends in prescribing antidepressants before and after an FDA advisory
      on suicidality risk in youths.
AB  - OBJECTIVE: This study evaluated the national trends in prescribing pharmacologic
      treatments for pediatric depression before and after a 2003 U.S. Food and Drug
      Administration advisory linking an increased risk of suicidality with
      antidepressants among pediatric patients with major depressive disorder. METHODS:
      National estimates on outpatient visits between 1998 and 2007 with a diagnosis of
      depression, a prescription for an antidepressant, or both among children ages 5
      to 17 and adults were obtained from the National Ambulatory Medical Care Survey
      and the National Hospital Ambulatory Medical Care Survey. RESULTS: Among
      children, depression visits increased from 1998-1999 to 2002-2003 (3.2 and 4.3
      million, respectively) but decreased to 3.2 million in 2006-2007. Antidepressant
      visits increased from 1998-1999 to 2002-2003 (3.4 and 7.6 million, respectively)
      but dropped to 6.7 million in 2006-2007. Depression visits with an antidepressant
      prescribed rose from 1998-1999 to 2002-2003 (1.7 and 2.8 million, respectively)
      but dropped in 2004-2005 and 2006-2007 (2.4 and 2.1 million, respectively).
      Nevertheless, the proportion of depression visits with an antidepressant
      prescribed, having risen from 54% in 1998-1999 to 66% in 2002-2003, remained
      stable in 2004-2005 (65%) and in 2006-2007 (64%), the result, seemingly, of more
      prescribing of antidepressants for major depressive disorder and less for other
      depression. Utilization patterns among adults were not interrupted. CONCLUSIONS:
      Children's depression visits and visits with an antidepressant prescribed dropped
      after the advisory, but children with major depressive disorder appeared no less
      likely to be prescribed antidepressants.

PMID- 21724785
TI  - Influence of caregivers' experiences on service use among children with attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: This study examined how prior experiences of caregivers of children
      with attention-deficit hyperactivity disorder (ADHD) leading up to treatment
      related to later service use. METHODS: The investigators interviewed caregivers
      of 48 children with ADHD recruited from outpatient clinic settings and recorded
      the children's medication use and clinic attendance six and 12 months later.
      Interview transcripts were analyzed to identify characteristic experiences, or
      themes, felt by the caregivers before seeking treatment. The investigators also
      looked for patterns in the way themes were endorsed. RESULTS: Caregivers'
      experiences with the children's ADHD were characterized by six main themes
      caregiver strain, attribution of meaning, perception of responsibility, problem
      solving approach, beliefs about ADHD treatment, and response to societal
      influences. Based on distinct patterns in which they endorsed the six themes,
      caregivers were classified as motivated by observation (high on theme of
      perception of responsibility and low on theme of caregiver strain; 27%),
      motivated by experience (positive attribution of meaning and beliefs about ADHD
      treatment and low on strain; 19%), motivated by strain (high on strain, uncertain
      attribution of meaning, and contradictory societal influences; 23%), and
      struggling with meaning (high on strain, nonmedical attribution of meaning; 31%).
      At 12 months, children of caregivers who were motivated by experience were the
      most likely and those struggling with meaning were the least likely to attend
      clinic appointments (89% and 53%, respectively, p=.017). The groups did not vary
      in medication use. CONCLUSIONS: Early identification of the factors influencing
      caregivers' use of services for children with ADHD may have implications for
      treatment retention.

PMID- 21724786
TI  - Role of the gender-linked norm of toughness in the decision to engage in
      treatment for depression.
AB  - OBJECTIVE: Given their prevalence and persuasive power in our culture, gender
      norms--commonly described as socially reinforced, learned expectations of what it
      means to be a man or a woman--likely contribute to sex differences in service
      utilization for depression. This study investigated whether sex differences in
      toughness, a gender-linked norm characterized by a desire to hide pain and
      maintain independence, were associated with a preference to wait for depression
      to resolve on its own without active professional treatment ("wait-and-see"
      approach). METHODS: Participants (N=1,051) in the California Behavioral Risk
      Factor Surveillance System (BRFSS) survey were contacted in a follow-on survey to
      assess toughness, the kind of treatment they would prefer were they to receive a
      diagnosis of depression, and current symptoms of depression. Participants who
      reported ever having been diagnosed as having a depressive disorder on the BRFSS
      were oversampled threefold. Analyses were conducted using linear and logistic
      regressions. RESULTS: Men and women who scored higher on toughness had a greater
      preference for the wait-and-see approach (OR=1.14, p<.01). Women were less likely
      to prefer the wait-and-see approach (OR=.58, p<.04) and scored lower on toughness
      (B=-.70, p<.01). Men's greater levels of toughness partially mediated the sex
      difference in treatment preferences (OR=.91, p<.03). CONCLUSIONS: Men's greater
      adherence to the toughness norm explained part of the sex difference observed in
      treatment-seeking preferences, but toughness undermined women's treatment seeking
      as well. Findings could be used to inform novel public health communications
      intended to attract both men and women to psychiatric services.

PMID- 21724787
TI  - Continuity of antipsychotic medication management for Medicaid patients with
      schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to examine whether medication refill
      behavior varies by the number of prescribers of antipsychotic medication a
      patient has. METHODS: A total of 7,868 patients with schizophrenia were
      identified from North Carolina Medicaid records for the period 2001-2003.
      Medication switching and adherence outcomes in 2003 were constructed from
      Medicaid pharmacy claims. Adherence was categorized into four levels
      (nonadherence, partial adherence, full adherence, or excess filler). Patients
      were stratified into four groups on the basis of the number of providers who
      prescribed antipsychotics in 2002 (one prescriber, two prescribers, three
      prescribers, or four or more prescribers). Medication switching was modeled via
      logistic regression, and the four-level adherence outcome was modeled via ordered
      logistic regression, with both regressions controlling for the number of
      prescribers, age, gender, race, and comorbidity. Medication switching in 2003 was
      also controlled for in the adherence regression. Predicted probabilities of being
      in the four adherence groups were estimated to examine the impact of the number
      of prescribers on adherence. RESULTS: Fifty-seven percent of Medicaid patients
      with schizophrenia had one prescriber for antipsychotic medication, 29% had two
      prescribers, 10% had three prescribers, and 4% had four or more prescribers in
      2002. Patients with more prescribers were significantly more likely than patients
      with one prescriber to switch medications (p<.01 for patients with three
      prescribers) and to be either fully adherent or excess fillers (p<.001).
      CONCLUSIONS: Patients with schizophrenia who received medication from multiple
      prescribers frequently changed medications and filled prescriptions too soon.
      Care coordination, such as with medical homes, may be effective in improving
      medication use in this vulnerable population.

PMID- 21724788
TI  - A learning collaborative of CMHCs and CHCs to support integration of behavioral
      health and general medical care.
AB  - OBJECTIVE: Integration of general medical and mental health services is a growing
      priority for safety-net providers. The authors describe a project that
      established a one-year learning collaborative focused on integration of services
      between community health centers (CHCs) and community mental health centers
      (CMHCs). Specific targets were treatment for general medical and psychiatric
      symptoms related to depression, bipolar disorder, alcohol use disorders, and
      metabolic syndrome. METHODS: This observational study used mixed methods.
      Quantitative measures included 15 patient-level health indicators, practice self
      assessment of resources and support for chronic disease self-management, and
      participant satisfaction. RESULTS: Sixteen CHC-CMHC pairs were selected for the
      learning collaborative series. One pair dropped out because of personnel
      turnover. All teams increased capacity on one or more patient health indicators.
      CHCs scored higher than CMHCs on support for chronic disease self-management.
      Participation in the learning collaborative increased self-assessment scores for
      CHCs and CMHCs. Participant satisfaction was high. Observations by faculty
      indicate that quality improvement challenges included tracking patient-level
      outcomes, workforce issues, and cross-agency communication. CONCLUSIONS: Even
      though numerous systemic barriers were encountered, the findings support existing
      literature indicating that the learning collaborative is a viable quality
      improvement approach for enhancing integration of general medical and mental
      health services between CHCs and CMHCs. Real-world implementation of evidence
      based guidelines presents challenges often absent in research. Technical
      resources and support, a stable workforce with adequate training, and adequate
      opportunities for collaborator communications are particular challenges for
      integrating behavioral and general medical services across CHCs and CMHCs.

PMID- 21724789
TI  - Comparison of first-episode and previously treated persons with psychosis found
      NGMI for a violent offense.
AB  - OBJECTIVE: Evidence has emerged of a higher risk of serious violence in first
      episode psychosis. This study compared the characteristics of two groups of
      persons with psychosis found not guilty of violent offenses on the grounds of
      mental illness (NGMI): those who had not yet been treated and those who had
      previously received treatment. METHODS: Demographic, clinical, and offense data
      were taken from psychiatric reports and court documents for persons found NGMI of
      homicide, attempted homicide, and assaults causing serious injury in the state of
      New South Wales, Australia. RESULTS: Between 1992 and 2008, 272 persons were
      found NGMI of homicide (N=138) or attempted homicide and assault resulting in
      serious injury (N=134). Schizophrenia-related psychosis was the most common
      diagnosis (N=234, 86%); 93 (34%) had a co-occurring substance use disorder. Of
      the 272 offenders, 124 (46%) were classified as being in their first episode of
      psychosis, including 72 (52%) of the homicide offenders and 52 (39%) of those who
      committed a nonlethal violent offense. Multiple logistic regression analysis
      found that compared with those who had received previous treatment for psychosis,
      the first-episode patients were younger, more likely to be from a non-English
      speaking country, and more likely to have used a firearm in the offense.
      CONCLUSIONS: The first episode of psychosis is a period of particular risk for
      homicide and serious violence. Younger age, language and cultural barriers to
      care, and greater availability of lethal means appear to contribute to an
      increased risk of homicide and of other serious violent offenses in first-episode
      psychosis.

PMID- 21724790
TI  - Barriers to receiving early care for PTSD: results from the Jerusalem trauma
      outreach and prevention study.
AB  - OBJECTIVES: Preventing posttraumatic stress disorder (PTSD) is a pressing public
      health need. Studies have shown significant barriers to obtaining early care.
      This study prospectively evaluated the acceptance of early assessment and
      treatment, the accuracy of recommending care, and the consequences of declining
      it. METHODS: Researchers undertook systematic outreach to survivors of traumatic
      events consecutively seen in a general hospital emergency department. Structured
      telephone interviews were conducted 9.5+/-3.2 days after the emergency visit.
      Persons with acute stress disorder symptoms were invited for clinical assessment.
      Those clinically assessed as having acute PTSD symptoms were offered treatment.
      Telephone interviews, conducted 224.9+/-39.1 days from the traumatic event,
      evaluated those included in the initial assessment and a random sample of 10% of
      those not included because they were deemed not to have experienced a traumatic
      event. RESULTS: Telephone calls were made to 5,286 individuals, and 5,053 were
      reached (96%). Of these, 4,743 (94%) agreed to a telephone interview, 1,502 were
      invited for a clinical assessment, 756 (50%) attended the assessment, 397 were
      eligible for treatment, and 296 (75%) started treatment. Declining clinical
      assessments and treatment were associated with less symptom reduction over time.
      The prevalence of PTSD among those deemed not to have experienced a traumatic
      event, not to need clinical assessment, and not to need treatment were,
      respectively, 4%, 11%, and 3%. CONCLUSIONS: Despite successful outreach, many
      symptomatic participants declined clinical care and subsequently recovered less
      well. Screening for DSM-IV PTSD criterion A effectively identified survivors at
      low risk for PTSD. Systematic outreach is costly and might be reserved for
      exceptionally traumatic events.

PMID- 21724792
TI  - Progress in workforce development since 2000: advanced training opportunities in
      public and community psychiatry.
AB  - A crisis in the behavioral health care workforce has drawn considerable attention
      from consumers, families, advocates, clinical professionals, and system
      administrators at local, state, and federal levels in the past decade. Its
      effects have been felt in the recruitment, retention, and performance of
      psychiatrists in the public sector, where a focus on biological aspects of
      illness and efforts to cut costs have made it difficult for public psychiatrists
      to engage meaningfully in leadership, consultation, prevention, and psychosocial
      interventions. An array of training opportunities has recently been created to
      meet the needs of community psychiatrists at various stages of their careers,
      from psychiatrists just beginning their careers to those who have been working as
      medical directors for several years. This article describes the development of
      these initiatives and their impact on public psychiatry in four key areas-
      training of experienced psychiatrists, ensuring retention of psychiatrists in
      community programs, providing fellowship training, and creating professional
      identity and pride. Although these programs constitute only initial steps,
      opportunities for psychiatrists to obtain advanced training in community
      psychiatry are much greater now than they were ten years ago. These initiatives
      will enhance the professional identity of community psychiatrists and provide a
      solid foundation for future development of public service psychiatry in the
      behavioral health workforce.

PMID- 21724791
TI  - Barriers to mental health care and predictors of treatment dropout in the South
      African Stress and Health Study.
AB  - OBJECTIVE: This study used data from the South African Stress and Health Study
      (SASH) to examine both structural and attitudinal barriers to treatment
      initiation among South Africans with mental disorders and to investigate
      predictors of treatment dropout. METHODS: Face-to-face interviews were conducted
      with 4,315 adult South Africans living in households or hostel quarters. The
      interview included a core diagnostic assessment of past-12-month mental disorders
      and assessments of disorder severity, service use, and barriers to treatment.
      Multivariate logistic regression models were used to determine predictors of not
      seeking treatment in relation to disorder severity and sociodemographic
      characteristics, as well as factors that were predictive of premature treatment
      discontinuation by participants who had received mental health treatment in the
      previous 12 months. Predictors of dropout were identified by cross-tabulation and
      discrete-time survival analysis. RESULTS: Of the 4,315 adults, 729 (16.9%
      weighted) met criteria for a mental disorder in the past 12 months. Across all
      levels of severity, the most frequently cited reason for not seeking professional
      treatment was a low perceived need for treatment. Among those who recognized the
      need but did not access treatment during the past 12 months (7.2%), attitudinal
      barriers to treatment seeking were reported more commonly than structural
      barriers (100% and 34%, respectively). Of the 182 respondents who received
      treatment (25% weighted), 20% discontinued prematurely. Various factors, such as
      substance use disorders and absence of health insurance, increased the odds of
      treatment dropout. CONCLUSIONS: Low rates of treatment seeking and high treatment
      dropout rates for common mental disorders among South Africans are a major
      concern. Public health efforts to improve treatment of mental disorders should
      consider the multiple influences on treatment initiation and discontinuation.

PMID- 21724793
TI  - A regional assessment of the quality of care for people with schizophrenia in The
      Netherlands.
AB  - This study examined the quality of mental health care for people with
      schizophrenia in eight regions in The Netherlands as assessed by the QUARTS:
      Quality Assessment of Regional Treatment Systems for Schizophrenia. The focus was
      on determining whether the introduction of multidisciplinary guidelines improved
      quality in service provision. METHODS: The QUARTS, a standardized interview
      instrument, addresses the availability of and satisfaction with services from the
      perspectives of clinicians, patients, families, and community organizations. The
      first QUARTS assessment was done about the time the guidelines were introduced in
      The Netherlands (2005), and the second was two to four years later. RESULTS: In
      all regions progress was made in the availability of care elements, although
      progress was limited for evidence-based rehabilitation interventions.
      CONCLUSIONS: Key clinicians in all regions perceived the guidelines as an
      important factor in improving the quality of schizophrenia care. QUARTS can be a
      helpful instrument for service monitoring and development.

PMID- 21724794
TI  - Disparities by education level in outcomes of a self-management intervention: the
      DELTA trial in The Netherlands.
AB  - OBJECTIVE: The study examined whether education level was associated with
      benefits derived from a self-management intervention. Because such interventions
      increase one's sense of control, it was hypothesized that persons with less
      education, who generally have a diminished sense of control, would derive greater
      benefit. METHODS: A randomized trial was conducted with 361 patients aged 60 and
      older with type 2 diabetes or chronic obstructive pulmonary disease and mild to
      moderate depression. The intervention provided individualized contacts (two to
      ten) with nurses who taught participants to take control of their disease.
      RESULTS: Positive effects on depression, health-related quality of life, feelings
      of mastery, and self-efficacy were confined to patients with more education;
      those with only a primary education did not benefit. CONCLUSIONS: Only more
      highly educated patients profited from a cognitive-behavioral approach to self
      management. Patients with chronic conditions who have less education may derive
      greater benefits if environmental adversities or lower cognitive abilities are
      taken into account.

PMID- 21724795
TI  - Access and outcomes for persons with psychotic and affective disorders receiving
      vocational rehabilitation services.
AB  - OBJECTIVE: This study examined the extent to which individuals with psychotic and
      affective disorders have access to vocational rehabilitation (VR) services and
      their employment and entitlement outcomes relative to persons with other
      disabilities. METHODS: National Rehabilitation Services Administration data were
      used for individuals who applied for VR services and whose cases were closed in
      2005-2007. The sample included persons with psychotic disorders (N=59,137),
      affective disorders (N=153,859), and other disabilities (N=652,829). RESULTS:
      Persons with psychiatric disabilities were less likely to get full access to VR
      services and had lower competitive employment rates at case closure compared with
      those with other disabilities. CONCLUSIONS: Individuals with psychotic and
      affective disorders had less access to the full complement of VR services and
      poorer outcomes. Implications include the need for additional training of VR
      providers to help them better meet the vocational needs of this population and
      greater support from mental health providers.

PMID- 21724796
TI  - Weight loss intervention for people with serious mental illness: a randomized
      controlled trial of the RENEW program.
AB  - OBJECTIVE: This study assessed phases one and two of a three-phase weight-loss
      program called RENEW--Recovering Energy Through Nutrition and Exercise for Weight
      Loss--among individuals with serious mental illness at four mental health
      centers. RENEW provides meal replacements twice daily and intensive instruction
      in nutrition and meal preparation, exercise, and goal setting for three months
      followed by three months of maintenance. METHODS: Individuals grouped by the
      psychiatric medication they took were assigned randomly to RENEW or to a control
      group. RESULTS: Participants who completed RENEW (N=47) had lost more weight on
      average than had the control group (N=42) at three and six months (weight loss of
      5.3 and 4.4 pounds, respectively, versus weight gain of .1 pounds and weight loss
      of .9 pounds, respectively; F=5.74, df=2 and 82, p=.005). Results did not vary on
      the basis of type of medication. CONCLUSIONS: Weight loss programs that address
      cognitive impairments that may accompany serious mental illness can be effective.

PMID- 21724797
TI  - An online portal on outcomes for Dutch service users.

PMID- 21724798
TI  - Feasibility of integrated depression care in an HIV clinic.

PMID- 21724800
TI  - Mental health standards for combat deployment.

PMID- 21724802
TI  - Coercion in treatment: researchers' perspectives.

PMID- 21724803
TI  - Comparing an intervention with treatment as usual.

PMID- 21724804
TI  - Development of tolerogenic dendritic cells and regulatory T cells favors
      exponential bacterial growth and survival during early respiratory tularemia.
AB  - Tularemia is a vector-borne zoonosis caused by Ft, a Gram-negative, facultative
      intracellular bacterium. Ft exists in two clinically relevant forms, the European
      biovar B (holarctica), which produces acute, although mild, self-limiting
      infections, and the more virulent United States biovar A (tularensis), which is
      often associated with pneumonic tularemia and more severe disease. In a mouse
      model of tularemia, respiratory infection with the virulence-attenuated Type B
      (LVS) or highly virulent Type A (SchuS4) strain engenders peribronchiolar and
      perivascular inflammation. Paradoxically, despite an intense neutrophilic
      infiltrate and high bacterial burden, T(h)1-type proinflammatory cytokines (e.g.,
      TNF, IL-1beta, IL-6, and IL-12) are absent within the first ~72 h of pulmonary
      infection. It has been suggested that the bacterium has the capacity to actively
      suppress or block NF-kappaB signaling, thus causing an initial delay in up
      regulation of inflammatory mediators. However, our previously published findings
      and those presented herein contradict this paradigm and instead, strongly support
      an alternative hypothesis. Rather than blocking NF-kappaB, Ft actually triggers
      TLR2-dependent NF-kappaB signaling, resulting in the development and activation
      of tDCs and the release of anti-inflammatory cytokines (e.g., IL-10 and TGF
      beta). In turn, these cytokines stimulate development and proliferation of
      T(regs) that may restrain T(h)1-type proinflammatory cytokine release early
      during tularemic infection. The highly regulated and overall anti-inflammatory
      milieu established in the lung is permissive for unfettered growth and survival
      of Ft. The capacity of Ft to evoke such a response represents an important immune
      evasive strategy.

PMID- 21724805
TI  - Monocytes differentiated with GM-CSF and IL-15 initiate Th17 and Th1 responses
      that are contact-dependent and mediated by IL-15.
AB  - Distinct types of DCs are generated from monocytes using GM-CSF with IL-4 (IL4
      DC) or IL-15 (IL15-DC). IL15-DCs are potent inducers of antigen-specific CD8(+) T
      cells, display a phenotype similar to CD14(+) cells commonly described in
      chronically inflamed tissues, and produce high levels of IL-1beta and IL-15 in
      response to TLR4 stimulation. As these cytokines promote Th17 responses, which
      are also associated with inflammatory diseases, I hypothesized that TLR-primed
      IL15-DCs favor Th17 activation over IL4-DCs. Compared with IL4-DCs, IL15-DCs
      stimulated with TLR agonists secreted significantly higher concentrations of the
      Th17-promoting factors, IL-1beta, IL-6, IL-23, and CCL20, and lower levels of the
      Th1 cytokine, IL-12. In addition, IL15-DCs and not IL4-DCs up-regulated IL-15 on
      the cell surface in response to TLR agonists. IL15-DCs primed with TLR3 or TLR4
      agonists triggered Th17 (IL-17, IL-22, and/or IFN-gamma) and Th1 (IFN-gamma)
      responses, whereas IL4-DCs primed with the same TLR agonists activated Th1 (IFN
      gamma) responses. Secretion of IL-17 and IFN-gamma required contact with TLR
      primed IL15-DC, and IFN-gamma production was mediated by membrane-bound IL-15.
      These findings identify key differences in monocyte-derived DCs, which impact
      adaptive immunity, and provide primary evidence that IL-15 promotes Th17 and Th1
      responses by skewing monocytes into IL15-DC.

PMID- 21724806
TI  - Specific expression of GPR56 by human cytotoxic lymphocytes.
AB  - We here report the existence of a new cluster of adhesion-GPCRs in human immune
      cells. Analysis of a comprehensive immune cell transcriptome dataset indicated
      that expression of the closely related receptors, GPR56, GPR97, and GPR114, is
      associated with single lymphocyte and granulocyte subsets. Applying flow
      cytometric analysis with newly generated mAb, we show that expression of GPR56 is
      restricted to cytotoxic NK and T lymphocytes, including CD8(+), CD4(+), and
      gammadelta T cells. Primary infection with human CMV, which generates a vast
      population of CD8(+) T cells with an effector phenotype, induced a strong
      increase in GPR56 expression in virus-specific CD8(+) T cells that remained
      detectable during latency. In NK-92 cells, ectopic expression of GPR56 inhibited
      spontaneous and SDF-1-stimulated cell migration. Our data suggest that GPR56
      expression is a common trait of human cytotoxic lymphocytes and might affect the
      migratory properties of these cells.

PMID- 21724807
TI  - Intestinal epithelial cell-derived integrin alphabeta6 plays an important role in
      the induction of regulatory T cells and inhibits an antigen-specific Th2
      response.
AB  - Toleroge nic DCs and Tregs are believed to play a critical role in oral
      tolerance. However, the mechanisms of the generation of tolerogenic DCs and
      activation of Tregs in the gut remain poorly understood. This study aims to
      dissect the molecular mechanisms by which IECs and protein antigen induce
      functional tolerogenic DCs and Tregs. Expression of alphavbeta6 by gut epithelial
      cell-derived exosomes, its coupling with food antigen, and their relationship
      with the development of functional tolerogenic DCs and Tregs were examined by
      using in vitro and in vivo approaches. The results show that IECs up-regulated
      the integrin alphavbeta6 upon uptake of antigens. The epithelial cell-derived
      exosomes entrapped and transported alphavbeta6 and antigens to the extracellular
      environment. The uptake of antigens alone induced DCs to produce LTGFbeta,
      whereas exosomes carrying alphavbeta6/antigen resulted in the production of
      abundant, active TGF-beta in DCs that conferred to DCs the tolerogenic
      properties. Furthermore, alphavbeta6/OVA-carrying, exosome-primed DCs were found
      to promote the production of active TGF-beta in Tregs. Thus, in vivo
      administration of alphavbeta6/OVA-laden exosomes induced the generation of Tregs
      and suppressed skewed Th2 responses toward food antigen in the intestine. Our
      study provides important molecular insights into the molecular mechanisms of Treg
      development by demonstrating an important role of IEC-derived exosomes carrying
      alphavbeta6 and food antigen in the induction of tolerogenic DCs and antigen
      specific Tregs.

PMID- 21724808
TI  - Imaging zebrafish development.

PMID- 21724809
TI  - Using intravital dyes to ubiquitously label embryonic zebrafish.

PMID- 21724810
TI  - Constructing a microinjection chamber for zebrafish eggs.

PMID- 21724811
TI  - Injecting zebrafish with DNA or RNA constructs encoding fluorescent protein
      reporters.

PMID- 21724812
TI  - Immersion freezing of cell monolayers for cryo-electron tomography.

PMID- 21724813
TI  - Immersion freezing of suspended particles and cells for cryo-electron microscopy.

PMID- 21724814
TI  - Labeling mitochondria with TMRM or TMRE.

PMID- 21724815
TI  - Labeling mitochondria with rhodamine 123.

PMID- 21724816
TI  - Setup and demonstration of a nanoelectrospray ionization source and tandem mass
      spectrometry.

PMID- 21724817
TI  - Generation and imaging of Brainbow mice.

PMID- 21724818
TI  - Electrophysiological recording from Drosophila taste sensilla.

PMID- 21724819
TI  - Electrophysiological recording from Drosophila olfactory sensilla.

PMID- 21724820
TI  - Characterization of helper-dependent adenoviral vectors.

PMID- 21724821
TI  - Rescue, amplification, and large-scale production of helper-dependent adenoviral
      vectors.

PMID- 21724822
TI  - Native agarose gel electrophoresis of multiprotein complexes.

PMID- 21724823
TI  - Live imaging of zebrafish development.

PMID- 21724824
TI  - Immersion freezing of biological specimens: rationale, principles, and
      instrumentation.

PMID- 21724825
TI  - Imaging the dynamics of biological processes via fast confocal microscopy and
      image processing.

PMID- 21724826
TI  - Generating and imaging multicolor Brainbow mice.

PMID- 21724827
TI  - CCD cameras for fluorescence imaging of living cells.

PMID- 21724828
TI  - The diverse functions of Dot1 and H3K79 methylation.
AB  - DOT1 (disruptor of telomeric silencing; also called Kmt4) was initially
      discovered in budding yeast in a genetic screen for genes whose deletion confers
      defects in telomeric silencing. Since the discovery ~10 years ago that Dot1 and
      its mammalian homolog, DOT1L (DOT1-Like), possess histone methyltransferase
      activity toward histone H3 Lys 79, great progress has been made in characterizing
      their enzymatic activities and the role of Dot1/DOT1L-mediated H3K79 methylation
      in transcriptional regulation, cell cycle regulation, and the DNA damage
      response. In addition, gene disruption in mice has revealed that mouse DOT1L
      plays an essential role in embryonic development, hematopoiesis, cardiac
      function, and the development of leukemia. The involvement of DOT1L enzymatic
      activity in leukemogenesis driven by a subset of MLL (mixed-lineage leukemia)
      fusion proteins raises the possibility of targeting DOT1L for therapeutic
      intervention.

PMID- 21724829
TI  - Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome assembly.
AB  - Histone H3 variant H3.3, while differing from canonical H3 (H3.1) by only five
      amino acids, is assembled into nucleosomes, along with histone H4, at genic
      regions by the histone chaperone HIRA, whereas H3.1 is assembled into nucleosomes
      in a CAF-1-dependent reaction. Here, we show that phosphorylation of histone H4
      Ser 47 (H4S47ph), catalyzed by the PAK2 kinase, promotes nucleosome assembly of
      H3.3-H4 and inhibits nucleosome assembly of H3.1-H4 by increasing the binding
      affinity of HIRA to H3.3-H4 and reducing association of CAF-1 with H3.1-H4. These
      results reveal a mechanism whereby H4S47ph distinctly regulates nucleosome
      assembly of H3.1 and H3.3.

PMID- 21724830
TI  - Tight protein-DNA interactions favor gene silencing.
AB  - The heterochromatin-like structure formed by the yeast silent information
      regulator complex (SIR) represses transcription at the silent mating type loci
      and telomeres. Here, we report that tight protein-DNA complexes induce ectopic
      recruitment of the SIR complex, promoting gene silencing and changes in
      subnuclear localization when cis-acting elements are nearby. Importantly, lack of
      the replication fork-associated helicase Rrm3 enhances this induced gene
      repression. Additionally, Sir3 and Sir4 are enriched genome-wide at natural
      replication pause sites, including tRNA genes. Consistently, inserting a tRNA
      gene promotes SIR-mediated silencing of a nearby gene. These results reveal that
      replication stress arising from tight DNA-protein interactions favors
      heterochromatin formation.

PMID- 21724831
TI  - Integrative analysis of gene amplification in Drosophila follicle cells:
      parameters of origin activation and repression.
AB  - In metazoans, how replication origins are specified and subsequently activated is
      not well understood. Drosophila amplicons in follicle cells (DAFCs) are genomic
      regions that undergo rereplication to increase DNA copy number. We identified all
      DAFCs by comparative genomic hybridization, uncovering two new amplicons in
      addition to four known previously. The complete identification of all DAFCs
      enabled us to investigate these in vivo replicons with respect to parameters of
      transcription, localization of the origin recognition complex (ORC), and histone
      acetylation, yielding important insights into gene amplification as a metazoan
      replication model. Significantly, ORC is bound across domains spanning 10 or more
      kilobases at the DAFC rather than at a specific site. Additionally, ORC is bound
      at many regions that do not undergo amplification, and, in contrast to cell
      culture, these regions do not correlate with high gene expression. As a
      developmental strategy, gene amplification is not the predominant means of
      achieving high expression levels, even in cells capable of amplification.
      Intriguingly, we found that, in some strains, a new amplicon, DAFC-22B, does not
      amplify, a consequence of distant repression of ORC binding and origin
      activation. This repression is alleviated when a fragment containing the origin
      is placed in different genomic contexts.

PMID- 21724832
TI  - Semaphorin 3E-Plexin-D1 signaling regulates VEGF function in developmental
      angiogenesis via a feedback mechanism.
AB  - Blood vessel networks are typically formed by angiogenesis, a process in which
      new vessels form by sprouting of endothelial cells from pre-existing vessels.
      This process is initiated by vascular endothelial growth factor (VEGF)-mediated
      tip cell selection and subsequent angiogenic sprouting. Surprisingly, we found
      that VEGF directly controls the expression of Plexin-D1, the receptor for the
      traditional repulsive axon guidance cue, semaphorin 3E (Sema3E). Sema3E-Plexin-D1
      signaling then negatively regulates the activity of the VEGF-induced Delta-like 4
      (Dll4)-Notch signaling pathway, which controls the cell fate decision between tip
      and stalk cells. Using the mouse retina as a model system, we show that Plexin-D1
      is selectively expressed in endothelial cells at the front of actively sprouting
      blood vessels and its expression is tightly controlled by VEGF secreted by
      surrounding tissues. Therefore, although the Sema3E secreted by retinal neurons
      is evenly distributed throughout the retina, Sema3E-Plexin-D1 signaling is
      spatially controlled by VEGF through its regulation of Plexin-D1. Moreover, we
      show that gain and loss of function of Sema3E and Plexin-D1 disrupts normal Dll4
      expression, Notch activity, and tip/stalk cell distribution in the retinal
      vasculature. Finally, the retinal vasculature of mice lacking sema3E or plexin-D1
      has an uneven growing front, a less-branched vascular network, and abnormal
      distribution of dll4-positive cells. Lowering Notch activity in the mutant mice
      can reverse this defect, solidifying the observation that Dll4-Notch signaling is
      regulated by Sema3E-Plexin-D1 and is required for its function in vivo. Together,
      these data reveal a novel role of Sema3E-Plexin-D1 function in modulating
      angiogenesis via a VEGF-induced feedback mechanism.

PMID- 21724833
TI  - Identification of PTPN23 as a novel regulator of cell invasion in mammary
      epithelial cells from a loss-of-function screen of the 'PTP-ome'.
AB  - We used an RNAi-mediated loss-of-function screen to study systematically the role
      of the protein tyrosine phosphatase (PTP) superfamily of enzymes in mammary
      epithelial cell motility in the absence or presence of the oncoprotein tyrosine
      kinase ERBB2. We report that although shRNAs directed against most of the PTP
      family were without effect, suppression of three PTPs-PRPN23, PTPRG, and PTPRR
      enhanced cell motility. Furthermore, we found that suppression of PTPN23, but not
      PTPRG or PTPRR, induced cell invasion. Suppression of PTPN23 increased E-cadherin
      internalization, impaired early endosome trafficking of E-cadherin, induced the
      expression of mesenchymal proteins, and caused cell scattering. The activity of
      SRC and beta-catenin was elevated when PTPN23 was suppressed. Moreover, we
      identified SRC, E-cadherin, and beta-catenin as direct substrates of PTPN23.
      Inhibition of SRC with the small molecular inhibitor SU6656 blocked the effects
      of PTPN23 depletion. These findings suggest that loss of PTPN23 may increase the
      activity of SRC and the phosphorylation status of the E-cadherin/beta-catenin
      signaling complex to promote tumor growth and invasive behavior in breast cancer.
      In addition, our studies highlight functional specificity among PTPs and reveal
      new roles for PTPs in mammary epithelial cell biology.

PMID- 21724834
TI  - Fine-tuning p53 activity through C-terminal modification significantly
      contributes to HSC homeostasis and mouse radiosensitivity.
AB  - Cell cycle regulation in hematopoietic stem cells (HSCs) is tightly controlled
      during homeostasis and in response to extrinsic stress. p53, a well-known tumor
      suppressor and transducer of diverse stress signals, has been implicated in
      maintaining HSC quiescence and self-renewal. However, the mechanisms that control
      its activity in HSCs, and how p53 activity contributes to HSC cell cycle control,
      are poorly understood. Here, we use a genetically engineered mouse to show that
      p53 C-terminal modification is critical for controlling HSC abundance during
      homeostasis and HSC and progenitor proliferation after irradiation. Preventing
      p53 C-terminal modification renders mice exquisitely radiosensitive due to
      defects in HSC/progenitor proliferation, a critical determinant for restoring
      hematopoiesis after irradiation. We show that fine-tuning the expression levels
      of the cyclin-dependent kinase inhibitor p21, a p53 target gene, contributes
      significantly to p53-mediated effects on the hematopoietic system. These results
      have implications for understanding cell competition in response to stresses
      involved in stem cell transplantation, recovery from adverse hematologic effects
      of DNA-damaging cancer therapies, and development of radioprotection strategies.

PMID- 21724836
TI  - Retraction. PRMT1-mediated arginine methylation of PIAS1 regulates STAT1
      signaling.

PMID- 21724837
TI  - Follicular thyroid neoplasms can be classified as low- and high-risk according to
      HBME-1 and Galectin-3 expression on liquid-based fine-needle cytology.
AB  - DESIGN: Fine-needle aspiration biopsy (FNAB) is the most reliable diagnostic tool
      in the diagnosis of thyroid nodules. A cytologic diagnosis of follicular neoplasm
      with atypical cells of undetermined significance (FN/AUS) implies that the
      selection of patients between surgery and follow-up is difficult. In this setting
      immunocytochemical stainings might be helpful. The efficacy of a panel made up of
      HBME-1 and Galectin-3 antibodies is evaluated in cases processed by liquid-based
      cytology (LBC). METHODS: Out of 7091 thyroid FNAB processed by LBC method, 120
      cases undergoing surgery successively were selected. These cases were classified
      as benign lesion (BL, eight cases), FN, including the ACUS category of the
      Bethesda classification (FN/AUS, 50 cases), suspicious for malignancy (SM, 59
      cases), and malignant neoplasm (MN, three cases). Immunostains for HBME-1 and
      Galectin-3 were carried out on the LBC slides. RESULTS: All MN and BL were
      histologically confirmed. FN/AUS and SM showed a malignancy risk of 24 and 72.9%
      respectively. The complete immunocytochemical panel was positive in 83.3% of the
      cases resulting in malignancy and negative in 87.5% of cases resulting in benign
      histology. Among the FN/AUS, the complete positive immunocytochemical panel was
      detected in 76.9% of cases resulting as malignant and the complete negative
      immunocytochemical panel was observed in 96.8% of cases resulting as benign at
      histology. CONCLUSIONS: The expression of HBME-1 and Galectin-3 in cases
      classified as FN/AUS on LBC-processed FNABs can effectively distinguish lesions,
      which need immediate surgery (high risk or FNH or Thy 3h) from those which can be
      followed-up (low risk or FNL or Thy 3l).

PMID- 21724835
TI  - Stem cell activation by light guides plant organogenesis.
AB  - Leaves originate from stem cells located at the shoot apical meristem. The
      meristem is shielded from the environment by older leaves, and leaf initiation is
      considered to be an autonomous process that does not depend on environmental
      cues. Here we show that light acts as a morphogenic signal that controls leaf
      initiation and stabilizes leaf positioning. Leaf initiation in tomato shoot
      apices ceases in the dark but resumes in the light, an effect that is mediated
      through the plant hormone cytokinin. Dark treatment also affects the subcellular
      localization of the auxin transporter PIN1 and the concomitant formation of auxin
      maxima. We propose that cytokinin is required for meristem propagation, and that
      auxin redirects cytokinin-inducible meristem growth toward organ formation. In
      contrast to common wisdom over the last 150 years, the light environment controls
      the initiation of lateral organs by regulating two key hormones: auxin and
      cytokinin.

PMID- 21724839
TI  - A critical review and meta-analysis of the association between overt
      hyperthyroidism and mortality.
AB  - BACKGROUND: Overt hyperthyroidism has been associated with cardiac arrhythmias,
      hypercoagulopathy, stroke, and pulmonary embolism, all of which may increase
      mortality. Some, but not all, studies show an increased mortality in patients
      with hyperthyroidism. This inconsistency may be due to differences in study
      design, characteristics of participants, or confounders. In order to test whether
      hyperthyroidism influences mortality, we performed a critical review and
      statistical meta-analysis. METHODS: Based on an electronic PubMed search, using
      the Medical Subject Heading words such as hyperthyroidism, thyrotoxicosis, and
      mortality or survival, case-control and cohort studies were selected and
      reviewed. Using meta-analysis, an overall relative risk (RR) of mortality was
      calculated. RESULTS: Eight studies fulfilled the inclusion criteria, six of which
      showed an increased all-cause mortality; seven studies, including 31,138 patients
      and 400,000 person years at risk, allowed calculation of mortality in a meta
      analysis. Based on this, the RR of overall mortality was 1.21 (95% confidence
      interval: 1.05-1.38). Analyses including studies considering setting, treatment,
      and control for co-morbidity did not significantly alter this finding. As the
      measured heterogeneity (I(2)) ranges from 89.1 to 98.3%, which is much higher
      than the 50% generally viewed on as a threshold, the statistical heterogeneity is
      very pronounced in the included studies. CONCLUSION: In patients diagnosed with
      hyperthyroidism, mortality is increased by ~ 20%. Future studies need to address
      the cause of hyperthyroidism, impact of type of therapy, time dependency, as well
      as the potential influence of confounding or genetic susceptibility before the
      question of causality can be answered.

PMID- 21724838
TI  - Long-acting pegylated human GH in children with GH deficiency: a single-dose,
      dose-escalation trial investigating safety, tolerability, pharmacokinetics and
      pharmacodynamics.
AB  - OBJECTIVE: GH replacement therapy currently requires daily injections, which may
      be inconvenient and distressing for young patients. This study determined the
      safety, tolerability, pharmacokinetics and pharmacodynamics of escalating single
      doses of a pegylated GH (NNC126-0083) developed for once-weekly administration,
      in children with GH deficiency (GHD). DESIGN AND METHODS: Thirty children (age
      >=6 and <=12 years, weight >=16 kg) were randomised to NNC126-0083 or daily GH
      treatment. The subjects discontinued their daily GH treatment 7-9 days before
      receiving NNC126-0083 at 0.01, 0.02, 0.04 or 0.06 mg protein/kg (n=22) or seven
      once-daily doses of GH at 0.035 mg protein/kg (n=8). RESULTS: NNC126-0083 was
      well tolerated, and no short-term safety or local tolerability issues were
      identified. After NNC126-0083 treatment, dose-dependent IGF1 increases were
      evident for maximum concentration (C(max)), but not area under the curve (AUC(0)(
      )(168 h)). Mean values for IGF1 AUC(0)(-)(168 h)/168 h and C(max) were higher for
      GH than for NNC126-0083, although the difference was not statistically
      significant for cohort's 0.06 mg protein/kg. At 0.06 mg protein/kg, the resulting
      IGF1 response began subsiding at ~3 days post-dose. CONCLUSION: Single doses of
      long-acting NNC126-0083 were safe and well tolerated in children with GHD.
      Increased IGF1 levels were observed in all NNC126-0083 dose groups; however, a
      satisfactory once-weekly IGF1 profile was not reached within the NNC126-0083 dose
      levels administered.

PMID- 21724840
TI  - Inter- and intra-observer assessment of the Galactogram Imaging Classification
      System (GICS).
AB  - BACKGROUND: A new system for the classification of galactograms is reported. To
      date, there is no universally accepted classification system. PURPOSE: To
      evaluate inter- and intra-observer agreement of the Galactogram Imaging
      Classification System (GICS) MATERIAL AND METHODS: Six observers with different
      levels of experience retrospectively evaluated 30 galactograms using the GICS.
      Images were reviewed independently twice within a four-week period. The kappa
      statistic was calculated for intra- and inter-observer variability. RESULTS: The
      kappa for inter-observer agreement was moderate to substantial (range 0.41-0.72).
      Overall, the intra-observer kappa values were excellent (range 0.80-0.94).
      CONCLUSION: The present study shows a good to very good inter- and intra-observer
      agreement with the GICS. We believe the GICS can be incorporated into daily
      practice.

PMID- 21724841
TI  - Vertebral artery occlusion with Amplatzer vascular plug 4 to prevent subsequent
      endoleak in stent-graft treatment of subclavian artery gunshot injury.
AB  - Endovascular treatment options have evolved in many ways and become an important
      alternative for open surgical repairs in various vascular territories. Herein, we
      present a case of an 18-year-old man with complex injury to the left subclavian
      artery and vein caused by a gunshot 4 months ago. After the gunshot, a high-flow
      fistula between the left subclavian artery and the vein occurred with
      pseudoaneurysm formation. This fistula led to a significant left subclavian steal
      phenomenon. A stent-graft was deployed along the injured left subclavian artery
      after embolization of the left vertebral artery by Amplatzer vascular plug 4 (AVP
      4) in order to prevent subsequent endoleak due to the subclavian steal syndrome.

PMID- 21724843
TI  - Essential role of endocytosis of the type II transmembrane serine protease
      TMPRSS6 in regulating its functionality.
AB  - The type II transmembrane serine protease TMPRSS6 (also known as matriptase-2)
      controls iron homeostasis through its negative regulation of expression of
      hepcidin, a key hormone involved in iron metabolism. Upstream of the hepcidin
      regulated signaling pathway, TMPRSS6 cleaves its target substrate hemojuvelin
      (HJV) at the plasma membrane, but the dynamics of the cell-surface expression of
      the protease have not been addressed. Here, we report that TMPRSS6 undergoes
      constitutive internalization in transfected HEK293 cells and in two human hepatic
      cell lines, HepG2 and primary hepatocytes, both of which express TMPRSS6
      endogenously. Cell surface-labeled TMPRSS6 was internalized and was detected in
      clathrin- and AP-2-positive vesicles via a dynamin-dependent pathway. The
      endocytosed TMPRSS6 next transited in early endosomes and then to lysosomes.
      Internalization of TMPRSS6 is dependent on specific residues within its N
      terminal cytoplasmic domain, as site-directed mutagenesis of these residues
      abrogated internalization and maintained the enzyme at the cell surface. Cells
      coexpressing these mutants and HJV produced significantly decreased levels of
      hepcidin compared with wild-type TMPRSS6 due to the sustained cleavage of HJV at
      the cell surface by TMPRSS6 mutants. Our results underscore for the first time
      the importance of TMPRSS6 trafficking at the plasma membrane in the regulation of
      hepcidin expression, an event that is essential for iron homeostasis.

PMID- 21724842
TI  - Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer.
AB  - Beginning with precursor lesions, aberrant DNA methylation marks the entire
      spectrum of prostate cancer progression. We mapped the global DNA methylation
      patterns in select prostate tissues and cell lines using MethylPlex-next
      generation sequencing (M-NGS). Hidden Markov model-based next-generation sequence
      analysis identified ~68,000 methylated regions per sample. While global CpG
      island (CGI) methylation was not differential between benign adjacent and cancer
      samples, overall promoter CGI methylation significantly increased from ~12.6% in
      benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues,
      respectively (P-value < 2 * 10(-16)). We found distinct patterns of promoter
      methylation around transcription start sites, where methylation occurred not only
      on the CGIs, but also on flanking regions and CGI sparse promoters. Among the
      6691 methylated promoters in prostate tissues, 2481 differentially methylated
      regions (DMRs) are cancer-specific, including numerous novel DMRs. A novel cancer
      specific DMR in the WFDC2 promoter showed frequent methylation in cancer (17/22
      tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC
      cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an
      epigenetic mechanism for alternate transcription start site utilization, and
      these modifications segregated into distinct regions when present on the same
      promoter. Finally, we observed differences in repeat element methylation,
      particularly LINE-1, between ERG gene fusion-positive and -negative cancers, and
      we confirmed this observation using pyrosequencing on a tissue panel. This
      comprehensive methylome map will further our understanding of epigenetic
      regulation in prostate cancer progression.

PMID- 21724844
TI  - The Mef2A transcription factor coordinately regulates a costamere gene program in
      cardiac muscle.
AB  - The Mef2 family of transcription factors regulates muscle differentiation, but
      the specific gene programs controlled by each member remain unknown.
      Characterization of Mef2A knock-out mice has revealed severe myofibrillar defects
      in cardiac muscle indicating a requirement for Mef2A in cytoarchitectural
      integrity. Through comprehensive expression analysis of Mef2A-deficient hearts,
      we identified a cohort of dysregulated genes whose products localize to the
      peripheral Z-disc/costamere region. Many of these genes are essential for
      costamere integrity and function. Here we demonstrate that these genes are
      directly regulated by Mef2A, establishing a mechanism by which Mef2A controls the
      costamere. In an independent model system, acute knockdown of Mef2A in primary
      neonatal cardiomyocytes resulted in profound malformations of myofibrils and
      focal adhesions accompanied by adhesion-dependent programmed cell death. These
      findings indicate a role for Mef2A in cardiomyocyte survival through regulation
      of costamere integrity. Finally, bioinformatics analysis identified over
      represented transcription factor-binding sites in this network of costamere
      promoters that may provide insight into the mechanism by which costamere genes
      are regulated by Mef2A. The global control of costamere gene expression adds
      another dimension by which this essential macromolecular complex may be regulated
      in health and disease.

PMID- 21724845
TI  - Molecular determinants within N terminus of Orai3 protein that control channel
      activation and gating.
AB  - STIM1 and Orai represent the key components of Ca(2+) release-activated Ca(2+)
      channels. Activation of Orai channels requires coupling of the C terminus of
      STIM1 to the N and C termini of Orai. Although the latter appears to be central
      in the interaction with STIM1, the role of the N terminus and particularly of the
      conserved region close to the first transmembrane sequence is less well
      understood. Here, we investigated in detail the functional role of this conserved
      region in Orai3 by stepwise deletions. Molecular determinants were mapped for the
      two modes of Orai3 activation via STIM1 or 2-aminoethoxydiphenyl borate (2-APB)
      and for current gating characteristics. Increasing N-terminal truncations
      revealed a progressive decrease of the specific fast inactivation of Orai3
      concomitant with diminished binding to calmodulin. STIM1-dependent activation of
      Orai3 was maintained as long as the second half of this conserved N-terminal
      domain was present. Further truncations abolished it, whereas Orai3 stimulation
      via 2-APB was partially retained. In aggregate, the N-terminal conserved region
      plays a multifaceted role in Orai3 current gating with distinct structural
      requirements for STIM1- and 2-APB-stimulated activation.

PMID- 21724846
TI  - A phosphodiesterase 2A isoform localized to mitochondria regulates respiration.
AB  - Mitochondria are central organelles in cellular energy metabolism, apoptosis, and
      aging processes. A signaling network regulating these functions was recently
      shown to include soluble adenylyl cyclase as a local source of the second
      messenger cAMP in the mitochondrial matrix. However, a mitochondrial cAMP
      degrading phosphodiesterase (PDE) necessary for switching off this cAMP signal
      has not yet been identified. Here, we describe the identification and
      characterization of a PDE2A isoform in mitochondria from rodent liver and brain.
      We find that mitochondrial PDE2A is located in the matrix and that the unique N
      terminus of PDE2A isoform 2 specifically leads to mitochondrial localization of
      this isoform. Functional assays show that mitochondrial PDE2A forms a local
      signaling system with soluble adenylyl cyclase in the matrix, which regulates the
      activity of the respiratory chain. Our findings complete a cAMP signaling cascade
      in mitochondria and have implications for understanding the regulation of
      mitochondrial processes and for their pharmacological modulation.

PMID- 21724848
TI  - The role of ITCH protein in human T-cell leukemia virus type 1 release.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) has two late domain (LD) motifs, PPPY
      and PTAP, which are important for viral budding. Mutations in the PPPY motif are
      more deleterious for viral release than changes in the PTAP motif. Several
      reports have shown that the interaction of PPPY with the WW domains of a Nedd4
      (neuronal precursor cell-expressed developmentally down-regulated-4) family
      ubiquitin ligase (UL) is a critical event in virus release. We tested nine
      members of the Nedd4 family ULs and found that ITCH is the main contributor to
      HTLV-1 budding. ITCH overexpression strongly inhibited release and infectivity of
      wild-type (wt) HTLV-1, but rescued the release of infectious virions with certain
      mutations in the PPPY motif. Electron microscopy showed either fewer or misshapen
      virus particles when wt HTLV-1 was produced in the presence of overexpressed
      ITCH, whereas mutants with changes in the PPPY motif yielded normal looking
      particles at wt level. The other ULs had significantly weaker or no effects on
      HTLV-1 release and infectivity except for SMURF-1, which caused enhanced release
      of wt and all PPPY(-) mutant particles. These particles were poorly infectious
      and showed abnormal morphology by electron microscopy. Budding and infectivity
      defects due to overexpression of ITCH and SMURF-1 were correlated with higher
      than normal ubiquitination of Gag. Only silencing of ITCH, but not of WWP1, WWP2,
      and Nedd4, resulted in a reduction of HTLV-1 budding from 293T cells. The binding
      efficiencies between the HTLV-1 LD and WW domains of different ULs as measured by
      mammalian two-hybrid interaction did not correlate with the strength of their
      effect on HTLV-1 budding.

PMID- 21724847
TI  - IQGAP1 protein binds human epidermal growth factor receptor 2 (HER2) and
      modulates trastuzumab resistance.
AB  - Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of
      breast cancers. Increased HER2 expression is an adverse prognostic factor and
      correlates with decreased patient survival. HER2-positive (HER2(+)) breast cancer
      is treated with trastuzumab. Unfortunately, some patients are intrinsically
      refractory to therapy, and many who do respond initially become resistant within
      1 year. Understanding the molecular mechanisms underlying HER2 signaling and
      trastuzumab resistance is essential to reduce breast cancer mortality. IQGAP1 is
      a ubiquitously expressed scaffold protein that contains multiple protein
      interaction domains. By regulating its binding partners IQGAP1 integrates
      signaling pathways, several of which contribute to breast tumorigenesis. We show
      here that IQGAP1 is overexpressed in HER2(+) breast cancer tissue and binds
      directly to HER2. Knockdown of IQGAP1 decreases HER2 expression, phosphorylation,
      signaling, and HER2-stimulated cell proliferation, effects that are all reversed
      by reconstituting cells with IQGAP1. Reducing IQGAP1 up-regulates p27, and
      blocking this increase attenuates the growth inhibitory effects of IQGAP1
      knockdown. Importantly, IQGAP1 is overexpressed in trastuzumab-resistant breast
      epithelial cells, and reducing IQGAP1 both augments the inhibitory effects of
      trastuzumab and restores trastuzumab sensitivity to trastuzumab-resistant SkBR3
      cells. These data suggest that inhibiting IQGAP1 function may represent a
      rational strategy for treating HER2(+) breast carcinoma.

PMID- 21724849
TI  - Regulation of intracellular manganese homeostasis by Kufor-Rakeb syndrome
      associated ATP13A2 protein.
AB  - Mutations in the ATP13A2 gene are associated with Kufor-Rakeb syndrome (KRS) and
      are found also in patients with various other types of parkinsonism. ATP13A2
      encodes a predicted lysosomal P5-type ATPase that plays important roles in
      regulating cation homeostasis. Disturbance of cation homeostasis in brains is
      indicated in Parkinson disease pathogenesis. In this study, we explored the
      biological function of ATP13A2 as well as the pathogenic mechanism of KRS
      pathogenic ATP13A2 mutants. The results revealed that wild-type ATP13A2, but not
      the KRS pathogenic ATP13A2 mutants, protected cells from Mn(2+)-induced cell
      death in mammalian cell lines and primary rat neuronal cultures. In addition,
      wild-type ATP13A2 reduced intracellular manganese concentrations and prevented
      cytochrome c release from mitochondria compared with the pathogenic mutants.
      Furthermore, endogenous ATP13A2 was up-regulated upon Mn(2+) treatment. Our
      results suggest that ATP13A2 plays important roles in protecting cells against
      manganese cytotoxicity via regulating intracellular manganese homeostasis. The
      study provides a potential mechanism of KRS and parkinsonism pathogenesis.

PMID- 21724850
TI  - Identification of bacterial target proteins for the salicylidene acylhydrazide
      class of virulence-blocking compounds.
AB  - A class of anti-virulence compounds, the salicylidene acylhydrazides, has been
      widely reported to block the function of the type three secretion system of
      several Gram-negative pathogens by a previously unknown mechanism. In this work
      we provide the first identification of bacterial proteins that are targeted by
      this group of compounds. We provide evidence that their mode of action is likely
      to result from a synergistic effect arising from a perturbation of the function
      of several conserved proteins. We also examine the contribution of selected
      target proteins to the pathogenicity of Yersinia pseudotuberculosis and to
      expression of virulence genes in Escherichia coli O157.

PMID- 21724851
TI  - Increased adipocyte S-nitrosylation targets anti-lipolytic action of insulin:
      relevance to adipose tissue dysfunction in obesity.
AB  - Protein S-nitrosylation is a reversible protein modification implicated in both
      physiological and pathophysiological regulation of protein function. In obesity,
      skeletal muscle insulin resistance is associated with increased S-nitrosylation
      of insulin-signaling proteins. However, whether adipose tissue is similarly
      affected in obesity and, if so, what are the causes and functional consequences
      of increased S-nitrosylation in this tissue are unknown. Total protein S
      nitrosylation was increased in intra-abdominal adipose tissue of obese humans and
      in high fat-fed or leptin-deficient ob/ob mice. Both the insulin receptor beta
      subunit and Akt were S-nitrosylated, correlating with body weight. Elevated
      protein and mRNA expression of inducible NO synthase and decreased protein levels
      of thioredoxin reductase were associated with increased adipose tissue S
      nitrosylation. Cultured differentiated pre-adipocyte cell lines exposed to the NO
      donors S-nitrosoglutathione (GSNO) or S-nitroso-N-acetylpenicillamine exhibited
      diminished insulin-stimulated phosphorylation of Akt but not of GSK3 nor of
      insulin-stimulated glucose uptake. Yet the anti-lipolytic action of insulin was
      markedly impaired in both cultured adipocytes and in mice injected with GSNO
      prior to administration of insulin. In cells, impaired ability of insulin to
      diminish phosphorylated PKA substrates in response to isoproterenol suggested
      impaired insulin-induced activation of PDE3B. Consistently, increased S
      nitrosylation of PDE3B was detected in adipose tissue of high fat-fed obese mice.
      Site-directed mutagenesis revealed that Cys-768 and Cys-1040, two putative sites
      for S-nitrosylation adjacent to the substrate-binding site of PDE3B, accounted
      for ~50% of its GSNO-induced S-nitrosylation. Collectively, PDE3B and the anti
      lipolytic action of insulin may constitute novel targets for increased S
      nitrosylation of adipose tissue in obesity.

PMID- 21724852
TI  - Delta-like 1/fetal antigen-1 (Dlk1/FA1) is a novel regulator of chondrogenic cell
      differentiation via inhibition of the Akt kinase-dependent pathway.
AB  - Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of
      Notch/Delta family that inhibits adipocyte and osteoblast differentiation;
      however, its role in chondrogenesis is still not clear. Thus, we overexpressed
      Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects on chondrogenic
      differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation
      as evidenced by reduction of cartilage nodule formation and gene expression of
      aggrecan, collagen Type II and X. Similar effects were obtained either by using
      Dlk1/FA1-conditioned medium or by addition of a purified, secreted, form of Dlk1
      (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were
      dose-dependent and occurred irrespective of the chondrogenic differentiation
      stage: proliferation, differentiation, maturation, or hypertrophic conversion.
      Overexpression or addition of the Dlk1/FA1 protein to the medium strongly
      inhibited the activation of Akt, but not the ERK1/2, or p38 MAPK pathways, and
      the inhibition of Akt by Dlk1/FA1 was mediated through PI3K activation.
      Interestingly, inhibition of fibronectin expression by siRNA rescued the Dlk1/FA1
      mediated inhibition of Akt, suggesting interaction of Dlk1/FA1 and fibronectin in
      chondrogenic cells. Our results identify Dlk1/FA1 as a novel regulator of
      chondrogenesis and suggest Dlk1/FA1 acts as an inhibitor of the PI3K/Akt pathways
      that leads to its inhibitory effects on chondrogenesis.

PMID- 21724853
TI  - Gamma-aminobutyric acid type B (GABA(B)) receptor internalization is regulated by
      the R2 subunit.
AB  - gamma-Aminobutyric acid type B (GABA(B)) receptors are important for slow
      synaptic inhibition in the CNS. The efficacy of inhibition is directly related to
      the stability of cell surface receptors. For GABA(B) receptors,
      heterodimerization between R1 and R2 subunits is critical for cell surface
      expression and signaling, but how this determines the rate and extent of receptor
      internalization is unknown. Here, we insert a high affinity alpha-bungarotoxin
      binding site into the N terminus of the R2 subunit and reveal its dominant role
      in regulating the internalization of GABA(B) receptors in live cells. To
      simultaneously study R1a and R2 trafficking, a new alpha-bungarotoxin binding
      site-labeling technique was used, allowing alpha-bungarotoxin conjugated to
      different fluorophores to selectively label R1a and R2 subunits. This approach
      demonstrated that R1a and R2 are internalized as dimers. In heterologous
      expression systems and neurons, the rates and extents of internalization for
      R1aR2 heteromers and R2 homomers are similar, suggesting a regulatory role for R2
      in determining cell surface receptor stability. The fast internalization rate of
      R1a, which has been engineered to exit the endoplasmic reticulum, was slowed to
      that of R2 by truncating the R1a C-terminal tail or by removing a dileucine motif
      in its coiled-coil domain. Slowing the rate of internalization by co-assembly
      with R2 represents a novel role for GPCR heterodimerization whereby R2 subunits,
      via their C terminus coiled-coil domain, mask a dileucine motif on R1a subunits
      to determine the surface stability of the GABA(B) receptor.

PMID- 21724855
TI  - Age-period-cohort analysis of primary bone cancer incidence rates in the United
      States (1976-2005).
AB  - BACKGROUND: Primary bone cancer comprises three major histologic types:
      osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS). Given the limited
      knowledge about the etiology of primary bone cancer, we undertook an age-period
      cohort (APC) analysis to determine whether incidence varied by birth cohort or
      calendar period. The purpose was to examine the temporal development of each bone
      cancer type and generate etiologic hypotheses via the observed birth cohort
      related changes. METHODS: An APC model was fitted to incidence data for U.S.
      whites for OS, ES, and CS obtained from nine registries of the Surveillance,
      Epidemiology, and End Results program, which covers about 10% of the U.S.
      population, 1976-2005. RESULTS: The incidence of OS decreased between 1976 and
      2005 among those aged over 60 years, a decline that occurred among patients with
      OS as their primary malignancy only. From 1986-1995 to 1996-2005, the incidence
      rate of CS among females of 20 to 69 years rose by about 50%, with rates
      increasing among consecutive cohorts born during 1935-1975. CS rates among males
      were stable, as were rates of ES. CONCLUSION: The risk reduction in OS as a
      primary malignancy at older ages could possibly be related to diminished exposure
      over time to bone-seeking radionuclides. The CS increase among females
      corresponds to birth cohorts with rising exposures to oral contraceptives and
      menopausal hormonal therapy. IMPACT: As the estrogen signaling pathway has been
      shown to stimulate proliferation of normal and malignant chondrocytes, estrogen
      exposure may increase the risk for CS. Further studies are warranted to clarify
      its possible etiological significance.

PMID- 21724854
TI  - A novel approach to exploring potential interactions among single-nucleotide
      polymorphisms of inflammation genes in gliomagenesis: an exploratory case-only
      study.
AB  - BACKGROUND: Despite extensive research on the topic, glioma etiology remains
      largely unknown. Exploration of potential interactions between single-nucleotide
      polymorphisms (SNP) of immune genes is a promising new area of glioma research.
      The case-only study design is a powerful and efficient design for exploring
      possible multiplicative interactions between factors that are independent of one
      another. The purpose of our study was to use this exploratory design to identify
      potential pair wise SNP-SNP interactions from genes involved in several different
      immune-related pathways for investigation in future studies. METHODS: The study
      population consisted of two case groups: 1,224 histologic confirmed, non-Hispanic
      white glioma cases from the United States and a validation population of 634
      glioma cases from the United Kingdom. Polytomous logistic regression, in which
      one SNP was coded as the outcome and the other SNP was included as the exposure,
      was utilized to calculate the ORs of the likelihood of cases simultaneously
      having the variant alleles of two different SNPs. Potential interactions were
      examined only between SNPs located in different genes or chromosomes. RESULTS:
      Using this data mining strategy, we found 396 significant SNP-SNP interactions
      among polymorphisms of immune-related genes that were present in both the U.S.
      and U.K. study populations. CONCLUSION: This exploratory study was conducted for
      the purpose of hypothesis generation, and thus has provided several new
      hypotheses that can be tested using traditional case-control study designs to
      obtain estimates of risk. IMPACT: This is the first study, to our knowledge, to
      take this novel approach to identifying SNP-SNP interactions relevant to glioma
      etiology.

PMID- 21724856
TI  - Assessment of hepatocyte growth factor in ovarian cancer mortality.
AB  - BACKGROUND: Invasive ovarian cancer is a significant cause of gynecologic cancer
      mortality. METHODS: We examined whether this mortality was associated with
      inherited variation in approximately 170 candidate genes/regions [993 single
      nucleotide polymorphisms (SNPs)] in a multistage analysis based initially on 312
      Mayo Clinic cases (172 deaths). Additional analyses used The Cancer Genome Atlas
      (TCGA; 127 cases, 62 deaths). For the most compelling gene, we immunostained Mayo
      Clinic tissue microarrays (TMA, 326 cases) and conducted consortium-based SNP
      replication analysis (2,560 cases, 1,046 deaths). RESULTS: The strongest initial
      mortality association was in HGF (hepatocyte growth factor) at rs1800793 (HR =
      1.7, 95% CI = 1.3-2.2, P = 2.0 * 10(-5)) and with overall variation in HGF (gene
      level test, P = 3.7 * 10(-4)). Analysis of TCGA data revealed consistent
      associations [e.g., rs5745709 (r(2) = 0.96 with rs1800793): TCGA HR = 2.4, CI =
      1.4-4.1, P = 2.2 * 10(-3); Mayo Clinic + TCGA HR = 1.6, CI = 1.3-1.9, P = 7.0 *
      10(-5)] and suggested genotype correlation with reduced HGF mRNA levels (P =
      0.01). In Mayo Clinic TMAs, protein levels of HGF, its receptor MET (C-MET), and
      phospho-MET were not associated with genotype and did not serve as an
      intermediate phenotype; however, phospho-MET was associated with reduced
      mortality (P = 0.01) likely due to higher expression in early-stage disease. In
      eight additional ovarian cancer case series, HGF rs5745709 was not associated
      with mortality (HR = 1.0, CI = 0.9-1.1, P = 0.87). CONCLUSIONS: We conclude that
      although HGF signaling is critical to migration, invasion, and apoptosis, it is
      unlikely that HGF genetic variation plays a major role in ovarian cancer
      mortality. Furthermore, any minor role is not related to genetically-determined
      expression. IMPACT: Our study shows the utility of multiple data types and
      multiple data sets in observational studies.

PMID- 21724857
TI  - Regulatory domain phosphorylation to distinguish the mechanistic basis underlying
      acute CFTR modulators.
AB  - Modulator compounds intended to overcome disease-causing mutations in the cystic
      fibrosis transmembrane conductance regulator (CFTR) show significant promise in
      clinical testing for cystic fibrosis. However, the mechanism(s) of action
      underlying these compounds are not fully understood. Activation of CFTR ion
      transport requires PKA-regulated phosphorylation of the regulatory domain (R-D)
      and dimerization of the nucleotide binding domains. Using a newly developed
      assay, we evaluated nine compounds including both CFTR potentatiators and
      activators discovered via various high-throughput screening strategies to acutely
      augment CFTR activity. We found considerable differences in the effects on R-D
      phosphorylation. Some (including UC(CF)-152) stimulated robust phosphorylation,
      and others had little effect (e.g., VRT-532 and VX-770). We then compared CFTR
      activation by UC(CF)-152 and VRT-532 in Ussing chamber studies using two
      epithelial models, CFBE41o(-) and Fischer rat thyroid cells, expressing various
      CFTR forms. UC(CF)-152 activated wild-type-, G551D-, and rescued F508del-CFTR
      currents but did not potentiate cAMP-mediated CFTR activation. In contrast, VRT
      532 moderately activated CFTR short-circuit current and strongly potentiated
      forskolin-mediated current. Combined with the result that UC(CF)-152, but not VRT
      532 or VX-770, acts by increasing CFTR R-D phosphorylation, these findings
      indicate that potentiation of endogenous cAMP-mediated activation of mutant CFTR
      is not due to a pathway involving augmented R-D phosphorylation. This study
      presents an assay useful to distinguish preclinical compounds by a crucial
      mechanism underlying CFTR activation, delineates two types of compound able to
      acutely augment CFTR activity (e.g., activators and potentiators), and
      demonstrates that a number of different mechanisms can be successfully employed
      to activate mutant CFTR.

PMID- 21724858
TI  - Balance of life and death in alveolar epithelial type II cells: proliferation,
      apoptosis, and the effects of cyclic stretch on wound healing.
AB  - After acute lung injury, repair of the alveolar epithelium occurs on a substrate
      undergoing cyclic mechanical deformation. While previous studies showed that
      mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the
      impact of cell death during repair was not determined. We examined epithelial
      repair during cyclic stretch (CS) in a scratch-wound model of primary rat
      alveolar type II (ATII) cells and found that CS altered the balance between
      proliferation and cell death. We measured cell migration, size, and density;
      intercellular gap formation; cell number, proliferation, and apoptosis;
      cytoskeletal organization; and focal adhesions in response to scratch wounding
      followed by CS for up to 24 h. Under static conditions, wounds were closed by 24
      h, but repair was inhibited by CS. Wounding stimulated cell motility and
      proliferation, actin and vinculin redistribution, and focal adhesion formation at
      the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated
      cytoskeletal reorganization, and attenuated focal adhesion formation. CS also
      caused significant intercellular gap formation compared with static cells. Our
      results suggest that CS alters several mechanisms of epithelial repair and that
      an imbalance occurs between cell death and proliferation that must be overcome to
      restore the epithelial barrier.

PMID- 21724859
TI  - Cystic fibrosis and the relationship between mucin and chloride secretion by
      cultures of human airway gland mucous cells.
AB  - We investigated how cystic fibrosis (CF) alters the relationship between Cl(-)
      and mucin secretion in cultures of non-CF and CF human tracheobronchial gland
      mucous (HTGM and CFTGM, respectively) cells. Biochemical studies showed that HTMG
      cells secreted typical airway mucins, and immunohistochemical studies showed that
      these cells expressed MUC1, MUC4, MUC5B, MUC8, MUC13, MUC16, and MUC20. Effects
      of cumulative doses of methacholine (MCh), phenylephrine (Phe), isoproterenol
      (Iso), and ATP on mucin and Cl(-) secretion were studied on HTGM and CFTGM
      cultures. Baseline mucin secretion was not significantly altered in CFTGM cells,
      and the increases in mucin secretion induced by mediators were unaltered (Iso,
      Phe) or slightly decreased (MCh, ATP). Across mediators, there was no correlation
      between the maximal increases in Cl(-) secretion and mucin secretion. In HTGM
      cells, the Cl(-) channel blocker, diphenylamine-2-carboxylic acid, greatly
      inhibited Cl(-) secretion but did not alter mucin release. In HTGM cells,
      mediators (10(-5) M) increased mucin secretion in the rank order ATP > Phe = Iso
      > MCh. They increased Cl(-) secretion in the sequence ATP > MCh ~ Iso > Phe. The
      responses in Cl(-) secretion to MCh, ATP, and Phe were unaltered by CF, but the
      response to Iso was greatly reduced. We conclude that mucin secretion by cultures
      of human tracheobronchial gland cells is independent of Cl(-) secretion, at
      baseline, and is unaltered in CF; that the ratio of Cl(-) secretion to mucus
      secretion varies markedly depending on mediator; and that secretions induced by
      stimulation of beta-adrenergic receptors will be abnormally concentrated in CF.

PMID- 21724860
TI  - NOS2 regulation of LPS-induced airway inflammation via S-nitrosylation of NF
      {kappa}B p65.
AB  - Inducible nitric oxide synthase (NOS2) expression is increased in the airway
      epithelium in acute inflammatory disorders although the physiological impact
      remains unclear. We have previously shown that NOS2 inhibits NF-kappaB (p50-p65)
      activation in respiratory epithelial cells by inducing S-nitrosylation of the p65
      monomer (SNO-p65). In addition, we have demonstrated that mouse lung SNO-p65
      levels are acutely depleted in a lipopolysaccharide (LPS) model of lung injury
      and that augmenting SNO-p65 levels before LPS treatment results in decreased
      airway epithelial NF-kappaB activation, airway inflammation, and lung injury. We
      now show that aerosolized LPS induces NOS2 expression in the respiratory
      epithelium concomitant with an increase in lung SNO-p65 levels and a decrease in
      airway NF-kappaB activity. Genetic deletion of NOS2 results in an absence of SNO
      p65 formation, persistent NF-kappaB activity in the respiratory epithelium, and
      prolonged airway inflammation. These results indicate that a primary function of
      LPS-induced NOS2 expression in the respiratory epithelium is to modulate the
      inflammatory response through deactivation of NF-kappaB via S-nitrosylation of
      p65, thereby counteracting the initial stimulus-coupled denitrosylation.

PMID- 21724861
TI  - Lipopolysaccharide-induced injury is more pronounced in fetal transgenic ErbB4
      deleted lungs.
AB  - Pulmonary ErbB4 deletion leads to a delay in fetal lung development, alveolar
      simplification, and lung function disturbances in adult mice. We generated a
      model of intrauterine infection in ErbB4 transgenic mice to study the additive
      effects of antenatal LPS administration and ErbB4 deletion during fetal lung
      development. Pregnant mice were treated intra-amniotically with an LPS dose of 4
      MUg at E17 of gestation. Lungs were analyzed 24 h later. A significant influx of
      inflammatory cells was seen in all LPS-treated lungs. In heterozygote control
      lungs, LPS treatment resulted in a delay of lung morphogenesis characterized by a
      significant increase in the fraction of mesenchyme, a decrease in gas exchange
      area, and disorganization of elastic fibers. Surfactant protein (Sftp)b and Sftpc
      were upregulated, but mRNA of Sftpb and Sftpc was downregulated compared with non
      LPS-treated controls. The mRNA of Sftpa1 and Sftpd was upregulated. In ErbB4
      deleted lungs, the LPS effects were more pronounced, resulting in a further delay
      in morphological development, a more pronounced inflammation in the parenchyma,
      and a significant higher increase in all Sftp. The effect on Sftpb and Sftpc mRNA
      was somewhat different, resulting in a significant increase. These results imply
      a major role of ErbB4 in LPS-induced signaling in structural and functional lung
      development.

PMID- 21724862
TI  - Angiotensin II and pulmonary fibrosis, a new twist on an old story.

PMID- 21724863
TI  - Remodeling of atrial ATP-sensitive K+ channels in a model of salt-induced
      elevated blood pressure.
AB  - Hypertension is associated with the development of atrial fibrillation; however,
      the electrophysiological consequences of this condition remain poorly understood.
      ATP-sensitive K(+) (K(ATP)) channels, which contribute to ventricular
      arrhythmias, are also expressed in the atria. We hypothesized that salt-induced
      elevated blood pressure (BP) leads to atrial K(ATP) channel activation and
      increased arrhythmia inducibility. Elevated BP was induced in mice with a high
      salt diet (HS) for 4 wk. High-resolution optical mapping was used to measure
      atrial arrhythmia inducibility, effective refractory period (ERP), and action
      potential duration at 90% repolarization (APD(90)). Excised patch clamping was
      performed to quantify K(ATP) channel properties and density. K(ATP) channel
      protein expression was also evaluated. Atrial arrhythmia inducibility was 22%
      higher in HS hearts compared with control hearts. ERP and APD(90) were
      significantly shorter in the right atrial appendage and left atrial appendage of
      HS hearts compared with control hearts. Perfusion with 1 MUM glibenclamide or 300
      MUM tolbutamide significantly decreased arrhythmia inducibility and prolonged
      APD(90) in HS hearts compared with untreated HS hearts. K(ATP) channel density
      was 156% higher in myocytes isolated from HS animals compared with control
      animals. Sulfonylurea receptor 1 protein expression was increased in the left
      atrial appendage and right atrial appendage of HS animals (415% and 372% of NS
      animals, respectively). In conclusion, K(ATP) channel activation provides a
      mechanistic link between salt-induced elevated BP and increased atrial arrhythmia
      inducibility. The findings of this study have important implications for the
      treatment and prevention of atrial arrhythmias in the setting of hypertensive
      heart disease and may lead to new therapeutic approaches.

PMID- 21724864
TI  - Acute exercise activates AMPK and eNOS in the mouse aorta.
AB  - Exercise can prevent endothelial cell (EC) dysfunction and atherosclerosis even
      in the absence of improvements in plasma lipids. However, the mechanisms
      responsible for these effects are incompletely understood. In this study we
      examined in mice whether an acute bout of exercise activates enzymes that could
      prevent EC dysfunction, such as AMP-activated protein kinase (AMPK) and
      endothelial nitric oxide synthase (eNOS). We also examined whether exercise
      alters known regulators of these enzymes. C57BL/6 mice underwent a single bout of
      exhaustive treadmill exercise after which their aortas were analyzed for
      activation of AMPK, AMPK regulatory proteins, eNOS, and various enzymes that,
      like AMPK, activate eNOS. We found that such exercise acutely activates both AMPK
      and eNOS in the whole aorta and that the magnitude of these effects correlated
      with both the distance run and activation of the AMPK regulatory proteins silent
      information regulator-1 (SIRT1)-LKB1 and CaMKKbeta. In contrast, Akt, PKA, PKG,
      and Src, other kinases known to activate eNOS, were unaffected.
      Immunohistochemical analysis revealed that AMPK and eNOS were both activated in
      the ECs of the aorta. This study provides the first evidence that an acute bout
      of exercise activates AMPK and eNOS in the endothelium of the aorta. The results
      also suggest that AMPK likely is the principal activator of eNOS in this setting
      and that its own activation may be mediated by both SIRT1-LKB1 and CaMKKbeta.

PMID- 21724865
TI  - A constituent-based model of age-related changes in conduit arteries.
AB  - In the present report, a constituent-based theoretical model of age-related
      changes in geometry and mechanical properties of conduit arteries is proposed.
      The model was based on the premise that given the time course of the load on an
      artery and the accumulation of advanced glycation end-products in the arterial
      tissue, the initial geometric dimensions and properties of the arterial tissue
      can be predicted by a solution of a boundary value problem for the governing
      equations that follow from finite elasticity, structure-based constitutive
      modeling within the constrained mixture theory, continuum damage theory, and
      global growth approach for stress-induced structure-based remodeling. An
      illustrative example of the age-related changes in geometry, structure,
      composition, and mechanical properties of a human thoracic aorta is considered.
      Model predictions were in good qualitative agreement with available experimental
      data in the literature. Limitations and perspectives for refining the model are
      discussed.

PMID- 21724867
TI  - Physiology: found in translation.

PMID- 21724866
TI  - A mathematical model of action potentials of mouse sinoatrial node cells with
      molecular bases.
AB  - Genetically modified mice are popular experimental models for studying the
      molecular bases and mechanisms of cardiac arrhythmia. A postgenome challenge is
      to classify the functional roles of genes in cardiac function. To unveil the
      functional role of various genetic isoforms of ion channels in generating cardiac
      pacemaking action potentials (APs), a mathematical model for spontaneous APs of
      mouse sinoatrial node (SAN) cells was developed. The model takes into account the
      biophysical properties of membrane ionic currents and intracellular mechanisms
      contributing to spontaneous mouse SAN APs. The model was validated by its ability
      to reproduce the physiological exceptionally short APs and high pacing rates of
      mouse SAN cells. The functional roles of individual membrane currents were
      evaluated by blocking their coding channels. The roles of intracellular Ca(2+)
      handling mechanisms on cardiac pacemaking were also investigated in the model.
      The robustness of model pacemaking behavior was evaluated by means of one- and
      two-parameter analyses in wide parameter value ranges. This model provides a
      predictive tool for cellular level outcomes of electrophysiological experiments.
      It forms the basis for future model development and further studies into complex
      pacemaking mechanisms as more quantitative experimental data become available.

PMID- 21724868
TI  - Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent
      mechanism.
AB  - In the vasculature, nitric oxide (NO) is generated by endothelial NO synthase
      (eNOS) in a calcium/calmodulin-dependent reaction. In the absence of the
      requisite eNOS cofactor tetrahydrobiopterin (BH(4)), NADPH oxidation is uncoupled
      from NO generation, leading to the production of superoxide. Although this
      phenomenon is apparent with purified enzyme, cellular studies suggest that
      formation of the BH(4) oxidation product, dihydrobiopterin, is the molecular
      trigger for eNOS uncoupling rather than BH(4) depletion alone. In the current
      study, we investigated the effects of both BH(4) depletion and oxidation on eNOS
      derived superoxide production in endothelial cells in an attempt to elucidate the
      molecular mechanisms regulating eNOS oxidase activity. Results demonstrated that
      pharmacological depletion of endothelial BH(4) does not result in eNOS oxidase
      activity, whereas BH(4) oxidation gave rise to significant eNOS-oxidase activity.
      These findings suggest that the endothelium possesses regulatory mechanisms,
      which prevent eNOS oxidase activity from pterin-free eNOS. Using a combination of
      gene silencing and pharmacological approaches, we demonstrate that eNOS-caveolin
      1 association is increased under conditions of reduced pterin bioavailability and
      that this sequestration serves to suppress eNOS uncoupling. Using small
      interfering RNA approaches, we demonstrate that caveolin-1 gene silencing
      increases eNOS oxidase activity to 85% of that observed under conditions of BH(4)
      oxidation. Moreover, when caveolin-1 silencing was combined with a
      pharmacological inhibitor of AKT, BH(4) depletion increased eNOS-derived
      superoxide to 165% of that observed with BH(4) oxidation. This study identifies a
      critical role of caveolin-1 in the regulation of eNOS uncoupling and provides new
      insight into the mechanisms through which disease-associated changes in caveolin
      1 expression may contribute to endothelial dysfunction.

PMID- 21724869
TI  - Diastolic dysfunction is associated with cardiac fibrosis in the senescence
      accelerated mouse.
AB  - Diastolic heart failure is a major cause of mortality in the elderly population.
      It is often preceded by diastolic dysfunction, which is characterized by impaired
      active relaxation and increased stiffness. We tested the hypothesis that
      senescence-prone (SAMP8) mice would develop diastolic dysfunction compared with
      senescence-resistant controls (SAMR1). Pulsed-wave Doppler imaging of the ratio
      of blood flow velocity through the mitral valve during early (E) vs. late (A)
      diastole was reduced from 1.3 +/- 0.03 in SAMR1 mice to 1.2 +/- 0.03 in SAMP8
      mice (P < 0.05). Tissue Doppler imaging of the early (E') and late (A') diastolic
      mitral annulus velocities found E' reduced from 25.7 +/- 0.9 mm/s in SAMR1 to
      21.1 +/- 0.8 mm/s in SAMP8 mice and E'/A' similarly reduced from 1.1 +/- 0.02 to
      0.8 +/- 0.03 in SAMR1 vs. SAMP8 mice, respectively (P < 0.05). Invasive
      hemodynamics revealed an increased slope of the end-diastolic pressure-volume
      relationship (0.5 +/- 0.05 vs. 0.8 +/- 0.14; P < 0.05), indicating increased left
      ventricular chamber stiffness. There were no differences in systolic function or
      mean arterial pressure; however, diastolic dysfunction was accompanied by
      increased fibrosis in the hearts of SAMP8 mice. In SAMR1 vs. SAMP8 mice,
      interstitial collagen area increased from 0.3 +/- 0.04 to 0.8 +/- 0.09% and
      perivascular collagen area increased from 1.0 +/- 0.11 to 1.6 +/- 0.14%.
      Transforming growth factor-beta and connective tissue growth factor gene
      expression were increased in the hearts of SAMP8 mice (P < 0.05 for all data). In
      summary, SAMP8 mice show increased fibrosis and diastolic dysfunction similar to
      those seen in humans with aging and may represent a suitable model for future
      mechanistic studies.

PMID- 21724871
TI  - Cerebral and myocardial blood flow responses to hypercapnia and hypoxia in
      humans.
AB  - In humans, cerebrovascular responses to alterations in arterial Pco(2) and Po(2)
      are well documented. However, few studies have investigated human coronary
      vascular responses to alterations in blood gases. This study investigated the
      extent to which the cerebral and coronary vasculatures differ in their responses
      to euoxic hypercapnia and isocapnic hypoxia in healthy volunteers. Participants
      (n = 15) were tested at rest on two occasions. On the first visit, middle
      cerebral artery blood velocity (V(P)) was assessed using transcranial Doppler
      ultrasound. On the second visit, coronary sinus blood flow (CSBF) was measured
      using cardiac MRI. For comparison with V(P), CSBF was normalized to the rate
      pressure product [an index of myocardial oxygen consumption; normalized (n)CSBF].
      Both testing sessions began with 5 min of euoxic [end-tidal Po(2) (Pet(O(2))) =
      88 Torr] isocapnia [end-tidal Pco(2) (Pet(CO(2))) = +1 Torr above resting
      values]. Pet(O(2)) was next held at 88 Torr, and Pet(CO(2)) was increased to 40
      and 45 Torr in 5-min increments. Participants were then returned to euoxic
      isocapnia for 5 min, after which Pet(O(2)) was decreased from 88 to 60, 52 and 45
      Torr in 5-min decrements. Changes in V(P) and nCSBF were normalized to isocapnic
      euoxic conditions and indexed against Pet(CO(2)) and arterial oxyhemoglobin
      saturation. The V(P) gain for euoxic hypercapnia (%/Torr) was significantly
      higher than nCSBF (P = 0.030). Conversely, the V(P) gain for isocapnic hypoxia
      (%/%desaturation) was not different from nCSBF (P = 0.518). These findings
      demonstrate, compared with coronary circulation, that the cerebral circulation is
      more sensitive to hypercapnia but similarly sensitive to hypoxia.

PMID- 21724870
TI  - Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced
      inflammatory responses in vivo.
AB  - Redox-active transition metal ions, such as iron and copper, may play an
      important role in vascular inflammation, which is an etiologic factor in
      atherosclerotic vascular diseases. In this study, we investigated whether
      tetrathiomolybdate (TTM), a highly specific copper chelator, can act as an anti
      inflammatory agent, preventing lipopolysaccharide (LPS)-induced inflammatory
      responses in vivo. Female C57BL/6N mice were daily gavaged with TTM (30 mg/kg
      body wt) or vehicle control. After 3 wk, animals were injected intraperitoneally
      with 50 MUg LPS or saline buffer and killed 3 h later. Treatment with TTM reduced
      serum ceruloplasmin activity by 43%, a surrogate marker of bioavailable copper,
      in the absence of detectable hepatotoxicity. The concentrations of both copper
      and molybdenum increased in various tissues, whereas the copper-to-molybdenum
      ratio decreased, consistent with reduced copper bioavailability. TTM treatment
      did not have a significant effect on superoxide dismutase activity in heart and
      liver. Furthermore, TTM significantly inhibited LPS-induced inflammatory gene
      transcription in aorta and heart, including vascular and intercellular adhesion
      molecule-1 (VCAM-1 and ICAM-1, respectively), monocyte chemotactic protein-1 (MCP
      1), interleukin-6, and tumor necrosis factor (TNF)-alpha (ANOVA, P < 0.05);
      consistently, protein levels of VCAM-1, ICAM-1, and MCP-1 in heart were also
      significantly lower in TTM-treated animals. Similar inhibitory effects of TTM
      were observed on activation of nuclear factor-kappaB (NF-kappaB) and activator
      protein-1 (AP-1) in heart and lungs. Finally, TTM significantly inhibited LPS
      induced increases of serum levels of soluble ICAM-1, MCP-1, and TNF-alpha (ANOVA,
      P < 0.05). These data indicate that copper chelation with TTM inhibits LPS
      induced inflammatory responses in aorta and other tissues of mice, most likely by
      inhibiting activation of the redox-sensitive transcription factors, NF-kappaB and
      AP-1. Therefore, copper appears to play an important role in vascular
      inflammation, and TTM may have value as an anti-inflammatory or anti-atherogenic
      agent.

PMID- 21724872
TI  - Pharmacokinetics of daikenchuto, a traditional Japanese medicine (kampo) after
      single oral administration to healthy Japanese volunteers.
AB  - The pharmacokinetics of daikenchuto (TJ-100), a pharmaceutical-grade traditional
      Japanese medicine, were investigated in healthy Japanese volunteers after a
      single oral administration of 2.5-, 5-, and 10-g doses. Six ingredients [hydroxy
      alpha-sanshool (HAS), hydroxy-beta-sanshool (HBS), [6]-shogaol (6S), [10]-shogaol
      (10S), ginsenoside Rb1(GRB1), and ginsenoside Rg1(GRG1)] of TJ-100 were
      determined by using liquid chromatography-tandem mass spectrometry. The results
      indicated that HAS, an ingredient derived from Zanthoxylum piperitum fruit,
      exhibited the highest plasma concentration among the six ingredients
      investigated. The plasma concentrations of HAS, HBS, 6S, and 10S reached the
      maximum concentration (approximately 400, 80, 0.14, and 0.6 ng/ml, respectively,
      after a 5-g administration of TJ-100) within 30 min after administration, and the
      mean half-life was approximately 2 h. Thus, these compounds were rapidly absorbed
      and eliminated. The plasma concentration of GRB1 reached the maximum
      concentration (2 ng/ml after a 5-g administration of TJ-100) at approximately 4 h
      after administration and the half-life of GRB1 was approximately 40 h. The plasma
      concentration of GRG1 was extremely low (<0.023 ng/ml). The pharmacokinetics of
      HAS, HBS, 6S, and 10S, were linear within the range of 2.5 to 10 g/day of TJ-100.
      On the other hand, the kinetics of GRB1 and GRG1 were not proportional to dosage,
      and plateauing was observed.

PMID- 21724873
TI  - Evidence of autoinduction heterogeneity via expression of the Agr system of
      Listeria monocytogenes at the single-cell level.
AB  - To investigate if the primary function of the Agr system of Listeria
      monocytogenes is to monitor cell density, we followed Agr expression in batch
      cultures, in which the autoinducer concentration was uniform, and in biofilms.
      Expression was heterogeneous, suggesting that the primary function of Agr is not
      to monitor population density.

PMID- 21724874
TI  - Poly-3-hydroxybutyrate metabolism in the type II methanotroph Methylocystis
      parvus OBBP.
AB  - Differences in carbon assimilation pathways and reducing power requirements among
      organisms are likely to affect the role of the storage polymer poly-3
      hydroxybutyrate (PHB). Previous researchers have demonstrated that PHB functions
      as a sole growth substrate in aerobic cultures enriched on acetate during periods
      of carbon deficiency, but it is uncertain how C(1) metabolism affects the role of
      PHB. In the present study, the type II methanotroph Methylocystis parvus OBBP did
      not replicate using stored PHB in the absence of methane, even when all other
      nutrients were provided in excess. When PHB-rich cultures of M. parvus OBBP were
      deprived of carbon and nitrogen for 48 h, they did not utilize significant
      amounts of stored PHB, and neither cell concentrations nor concentrations of
      total suspended solids changed significantly. When methane and nitrogen both were
      present, PHB and methane were consumed simultaneously. Cells with PHB had
      significantly higher specific growth rates than cells lacking PHB. The addition
      of formate (a source of reducing power) to PHB-rich cells delayed PHB
      consumption, but the addition of glyoxylate (a source of C(2) units) did not.
      This and results from other researchers suggest that methanotrophic PHB
      metabolism is linked to the supply of reducing power as opposed to the supply of
      C(2) units for synthesis.

PMID- 21724875
TI  - Regime shift and microbial dynamics in a sequencing batch reactor for
      nitrification and anammox treatment of urine.
AB  - The microbial population and physicochemical process parameters of a sequencing
      batch reactor for nitrogen removal from urine were monitored over a 1.5-year
      period. Microbial community fingerprinting (automated ribosomal intergenic spacer
      analysis), 16S rRNA gene sequencing, and quantitative PCR on nitrogen cycle
      functional groups were used to characterize the microbial population. The reactor
      combined nitrification (ammonium oxidation)/anammox with organoheterotrophic
      denitrification. The nitrogen elimination rate initially increased by 400%,
      followed by an extended period of performance degradation. This phase was
      characterized by accumulation of nitrite and nitrous oxide, reduced anammox
      activity, and a different but stable microbial community. Outwashing of anammox
      bacteria or their inhibition by oxygen or nitrite was insufficient to explain
      reactor behavior. Multiple lines of evidence, e.g., regime-shift analysis of
      chemical and physical parameters and cluster and ordination analysis of the
      microbial community, indicated that the system had experienced a rapid transition
      to a new stable state that led to the observed inferior process rates. The events
      in the reactor can thus be interpreted to be an ecological regime shift.
      Constrained ordination indicated that the pH set point controlling cycle
      duration, temperature, airflow rate, and the release of nitric and nitrous oxides
      controlled the primarily heterotrophic microbial community. We show that by
      combining chemical and physical measurements, microbial community analysis and
      ecological theory allowed extraction of useful information about the causes and
      dynamics of the observed process instability.

PMID- 21724876
TI  - Analysis and manipulation of aspartate pathway genes for L-lysine overproduction
      from methanol by Bacillus methanolicus.
AB  - We investigated the regulation and roles of six aspartate pathway genes in L
      lysine overproduction in Bacillus methanolicus: dapG, encoding aspartokinase I
      (AKI); lysC, encoding AKII; yclM, encoding AKIII; asd, encoding aspartate
      semialdehyde dehydrogenase; dapA, encoding dihydrodipicolinate synthase; and
      lysA, encoding meso-diaminopimelate decarboxylase. Analysis of the wild-type
      strain revealed that in vivo lysC transcription was repressed 5-fold by L-lysine
      and induced 2-fold by dl-methionine added to the growth medium. Surprisingly,
      yclM transcription was repressed 5-fold by dl-methionine, while the dapG, asd,
      dapA, and lysA genes were not significantly repressed by any of the aspartate
      pathway amino acids. We show that the L-lysine-overproducing classical B.
      methanolicus mutant NOA2#13A52-8A66 has-in addition to a hom-1 mutation
      chromosomal mutations in the dapG coding region and in the lysA promoter region.
      No mutations were found in its dapA, lysC, asd, and yclM genes. The mutant dapG
      gene product had abolished feedback inhibition by meso-diaminopimelate in vitro,
      and the lysA mutation was accompanied by an elevated (6-fold) lysA transcription
      level in vivo. Moreover, yclM transcription was increased 16-fold in mutant
      strain NOA2#13A52-8A66 compared to the wild-type strain. Overexpression of wild
      type and mutant aspartate pathway genes demonstrated that all six genes are
      important for L-lysine overproduction as tested in shake flasks, and the effects
      were dependent on the genetic background tested. Coupled overexpression of up to
      three genes resulted in additive (above 80-fold) increased L-lysine production
      levels.

PMID- 21724877
TI  - Semicontinuous culture of Magnetospirillum gryphiswaldense MSR-1 cells in an
      autofermentor by nutrient-balanced and isosmotic feeding strategies.
AB  - An improved strategy was developed for the high-density culture of
      Magnetospirillum gryphiswaldense strain MSR-1 and large-scale magnetosome
      production in both 7.5- and 42-liter autofermentors. By using a nutrient-balanced
      feeding strategy and the replacement of carbon and nitrogen sources to reduce
      accumulation of Na(+) and Cl(-) ions, we reduced the factors that tend to inhibit
      cell growth, particularly the increase of osmotic potential. Semicontinuous
      culture was thereby achieved in the autofermentor for the first time. When the
      cells were harvested at 36 and 73 h, magnetosome yields (dry weight) as high as
      168.3 and 83.5 mg/liter/day, respectively, were achieved. These values were,
      respectively, approximately 10 and 5 times higher than the yields achieved in
      previous studies and represent a significant improvement in magnetosome
      production efficiency.

PMID- 21724878
TI  - Comparison of growth rates of aerobic anoxygenic phototrophic bacteria and other
      bacterioplankton groups in coastal Mediterranean waters.
AB  - Growth is one of the basic attributes of any living organism. Surprisingly, the
      growth rates of marine bacterioplankton are only poorly known. Current data
      suggest that marine bacteria grow relatively slowly, having generation times of
      several days. However, some bacterial groups, such as the aerobic anoxygenic
      phototrophic (AAP) bacteria, have been shown to grow much faster. Two
      manipulation experiments, in which grazing, viruses, and resource competition
      were reduced, were conducted in the coastal Mediterranean Sea (Blanes Bay
      Microbial Observatory). The growth rates of AAP bacteria and of several important
      phylogenetic groups (the Bacteroidetes, the alphaproteobacterial groups
      Roseobacter and SAR11, and the Gammaproteobacteria group and its subgroups the
      Alteromonadaceae and the NOR5/OM60 clade) were calculated from changes in cell
      numbers in the manipulation treatments. In addition, we examined the role that
      top-down (mortality due to grazers and viruses) and bottom-up (resource
      availability) factors play in determining the growth rates of these groups.
      Manipulations resulted in an increase of the growth rates of all groups studied,
      but its extent differed largely among the individual treatments and among the
      different groups. Interestingly, higher growth rates were found for the AAP
      bacteria (up to 3.71 day-1) and for the Alteromonadaceae (up to 5.44 day-1), in
      spite of the fact that these bacterial groups represented only a very low
      percentage of the total prokaryotic community. In contrast, the SAR11 clade,
      which was the most abundant group, was the slower grower in all treatments. Our
      results show that, in general, the least abundant groups exhibited the highest
      rates, whereas the most abundant groups were those growing more slowly,
      indicating that some minor groups, such the AAP bacteria, very likely contribute
      much more to the recycling of organic matter in the ocean than what their
      abundances alone would predict.

PMID- 21724879
TI  - Gpd1 and Gpd2 fine-tuning for sustainable reduction of glycerol formation in
      Saccharomyces cerevisiae.
AB  - Gpd1 and Gpd2 are the two isoforms of glycerol 3-phosphate dehydrogenase (GPDH),
      which is the rate-controlling enzyme of glycerol formation in Saccharomyces
      cerevisiae. The two isoenzymes play crucial roles in osmoregulation and redox
      balancing. Past approaches to increase ethanol yield at the cost of reduced
      glycerol yield have most often been based on deletion of either one or two
      isogenes (GPD1 and GPD2). While single deletions of GPD1 or GPD2 reduced glycerol
      formation only slightly, the gpd1Delta gpd2Delta double deletion strain produced
      zero glycerol but showed an osmosensitive phenotype and abolished anaerobic
      growth. Our current approach has sought to generate "intermediate" phenotypes by
      reducing both isoenzyme activities without abolishing them. To this end, the GPD1
      promoter was replaced in a gpd2Delta background by two lower-strength TEF1
      promoter mutants. In the same manner, the activity of the GPD2 promoter was
      reduced in a gpd1Delta background. The resulting strains were crossed to obtain
      different combinations of residual GPD1 and GPD2 expression levels. Among our
      engineered strains we identified four candidates showing improved ethanol yields
      compared to the wild type. In contrast to a gpd1Delta gpd2Delta double-deletion
      strain, these strains were able to completely ferment the sugars under quasi
      anaerobic conditions in both minimal medium and during simultaneous
      saccharification and fermentation (SSF) of liquefied wheat mash (wheat
      liquefact). This result implies that our strains can tolerate the ethanol
      concentration at the end of the wheat liquefact SSF (up to 90 g liter(-1)).
      Moreover, a few of these strains showed no significant reduction in osmotic
      stress tolerance compared to the wild type.

PMID- 21724880
TI  - Effect of soil clay content on RNA isolation and on detection and quantification
      of bacterial gene transcripts in soil by quantitative reverse transcription-PCR.
AB  - In this study, we evaluated the effect of soil clay content on RNA isolation and
      on quantitative reverse transcription-PCR (qRT-PCR) quantification of microbial
      gene transcripts. The amount of clay significantly altered RNA isolation yields
      and qRT-PCR analyses. Recommendations are made for quantifying microbial gene
      transcripts in soil samples varying in clay content.

PMID- 21724881
TI  - Geographic distribution of secondary metabolite genes in the marine actinomycete
      Salinispora arenicola.
AB  - The molecular fingerprinting technique terminal-restriction fragment length
      polymorphism (T-RFLP) was used in combination with sequence-based approaches to
      evaluate the geographic distribution of secondary metabolite biosynthetic genes
      in strains of the marine actinomycete Salinispora arenicola. This study targeted
      ketosynthase (KS) domains from type I polyketide synthase (PKS) genes and
      revealed four distinct clusters, the largest of which was comprised of strains
      from all six global locations sampled. The remaining strains fell into three
      smaller clusters comprised of strains derived entirely from the Red Sea, the Sea
      of Cortez, or around the Island of Guam. These results reveal variation in the
      secondary metabolite gene collectives maintained by strains that are largely
      clonal at the 16S rRNA level. The location specificities of the three smaller
      clusters provide evidence that collections of secondary metabolite genes in
      subpopulations of S. arenicola are endemic to these locations. Cloned KS
      sequences support the maintenance of distinct sets of biosynthetic genes in the
      strains associated with each cluster and include four that had not previously
      been detected in S. arenicola. Two of these new sequences were observed only in
      strains derived from Guam or the Sea of Cortez. Transcriptional analysis of one
      of the new KS sequences in conjunction with the production of the polyketide
      arenicolide A supports a link between this sequence and the associated
      biosynthetic pathway. From the perspective of natural product discovery, these
      results suggest that screening populations from distant locations can enhance the
      discovery of new natural products and provides further support for the use of
      molecular fingerprinting techniques, such as T-RFLP, to rapidly identify strains
      that possess distinct sets of biosynthetic genes.

PMID- 21724882
TI  - Involvement of the pleiotropic drug resistance response, protein kinase C
      signaling, and altered zinc homeostasis in resistance of Saccharomyces cerevisiae
      to diclofenac.
AB  - Diclofenac is a widely used analgesic drug that can cause serious adverse drug
      reactions. We used Saccharomyces cerevisiae as a model eukaryote with which to
      elucidate the molecular mechanisms of diclofenac toxicity and resistance.
      Although most yeast cells died during the initial diclofenac treatment, some
      survived and started growing again. Microarray analysis of the adapted cells
      identified three major processes involved in diclofenac detoxification and
      tolerance. In particular, pleiotropic drug resistance (PDR) genes and genes under
      the control of Rlm1p, a transcription factor in the protein kinase C (PKC)
      pathway, were upregulated in diclofenac-adapted cells. We tested if these
      processes or pathways were directly involved in diclofenac toxicity or
      resistance. Of the pleiotropic drug resistance gene products, the multidrug
      transporter Pdr5p was crucially important for diclofenac tolerance. Furthermore,
      deletion of components of the cell wall stress-responsive PKC pathway increased
      diclofenac toxicity, whereas incubation of cells with the cell wall stressor
      calcofluor white before the addition of diclofenac decreased its toxicity. Also,
      diclofenac induced flocculation, which might trigger the cell wall alterations.
      Genes involved in ribosome biogenesis and rRNA processing were downregulated, as
      were zinc-responsive genes. Paradoxically, deletion of the zinc-responsive
      transcription factor Zap1p or addition of the zinc chelator 1,10-phenanthroline
      significantly increased diclofenac toxicity, establishing a regulatory role for
      zinc in diclofenac resistance. In conclusion, we have identified three new
      pathways involved in diclofenac tolerance in yeast, namely, Pdr5p as the main
      contributor to the PDR response, cell wall signaling via the PKC pathway, and
      zinc homeostasis, regulated by Zap1p.

PMID- 21724883
TI  - Microbial diversity in anaerobic sediments at Rio Tinto, a naturally acidic
      environment with a high heavy metal content.
AB  - The Tinto River is an extreme environment located at the core of the Iberian
      Pyritic Belt (IPB). It is an unusual ecosystem due to its size (100 km long),
      constant acidic pH (mean pH, 2.3), and high concentration of heavy metals, iron,
      and sulfate in its waters, characteristics that make the Tinto River Basin
      comparable to acidic mine drainage (AMD) systems. In this paper we present an
      extensive survey of the Tinto River sediment microbiota using two culture
      independent approaches: denaturing gradient gel electrophoresis and cloning of
      16S rRNA genes. The taxonomic affiliation of the Bacteria showed a high degree of
      biodiversity, falling into 5 different phyla: Proteobacteria, Firmicutes,
      Bacteroidetes, Acidobacteria, and Actinobacteria; meanwhile, all the Archaea were
      affiliated with the order Thermoplasmatales. Microorganisms involved in the iron
      (Acidithiobacillus ferrooxidans, Sulfobacillus spp., Ferroplasma spp., etc.),
      sulfur (Desulfurella spp., Desulfosporosinus spp., Thermodesulfobium spp., etc.),
      and carbon (Acidiphilium spp., Bacillus spp., Clostridium spp., Acidobacterium
      spp., etc.) cycles were identified, and their distribution was correlated with
      physicochemical parameters of the sediments. Ferric iron was the main electron
      acceptor for the oxidation of organic matter in the most acid and oxidizing
      layers, so acidophilic facultative Fe(III)-reducing bacteria appeared widely in
      the clone libraries. With increasing pH, the solubility of iron decreases and
      sulfate-reducing bacteria become dominant, with the ecological role of
      methanogens being insignificant. Considering the identified microorganisms-which,
      according to the rarefaction curves and Good's coverage values, cover almost all
      of the diversity-and their corresponding metabolism, we suggest a model of the
      iron, sulfur, and organic matter cycles in AMD-related sediments.

PMID- 21724884
TI  - Microbial removal of atmospheric carbon tetrachloride in bulk aerobic soils.
AB  - Atmospheric concentrations of carbon tetrachloride (CCl(4)) were removed by bulk
      aerobic soils from tropical, subtropical, and boreal environments. Removal was
      observed in all tested soil types, indicating that the process was widespread.
      The flux measured in field chamber experiments was 0.24 +/- 0.10 nmol CCl(4)
      (m(2) day)(-1) (average +/- standard deviation [SD]; n = 282). Removal of CCl(4)
      and removal of methane (CH(4)) were compared to explore whether the two processes
      were linked. Removal of both gases was halted in laboratory samples that were
      autoclaved, dry heated, or incubated in the presence of mercuric chloride
      (HgCl(2)). In marl soils, treatment with antibiotics such as tetracycline and
      streptomycin caused partial inhibition of CCl(4) (50%) and CH(4) (76%) removal,
      but removal was not affected in soils treated with nystatin or myxothiazol. These
      data indicated that bacteria contributed to the soil removal of CCl(4) and that
      microeukaryotes may not have played a significant role. Amendments of methanol,
      acetate, and succinate to soil samples enhanced CCl(4) removal by 59%, 293%, and
      72%, respectively. Additions of a variety of inhibitors and substrates indicated
      that nitrification, methanogenesis, or biological reduction of nitrate, nitrous
      oxide, or sulfate (e.g., occurring in possible anoxic microzones) did not play a
      significant role in the removal of CCl(4). Methyl fluoride inhibited removal of
      CH(4) but not CCl(4), indicating that CH(4) and CCl(4) removals were not directly
      linked. Furthermore, CCl(4) removal was not affected in soils amended with copper
      sulfate or methane, supporting the results with MeF and suggesting that the
      observed CCl(4) removal was not significantly mediated by methanotrophs.

PMID- 21724885
TI  - Characterization of Planctomyces limnophilus and development of genetic tools for
      its manipulation establish it as a model species for the phylum Planctomycetes.
AB  - Planctomycetes represent a remarkable clade in the domain Bacteria because they
      play crucial roles in global carbon and nitrogen cycles and display cellular
      structures that closely parallel those of eukaryotic cells. Studies on
      Planctomycetes have been hampered by the lack of genetic tools, which we
      developed for Planctomyces limnophilus.

PMID- 21724887
TI  - Additional effects of silver nanoparticles on bactericidal efficiency depend on
      calcination temperature and dip-coating speed.
AB  - There is an increasing interest in the application of photocatalytic properties
      for disinfection of surfaces, air, and water. Titanium dioxide is widely used as
      a photocatalyst, and the addition of silver reportedly enhances its bactericidal
      action. However, the synergy of silver nanoparticles and TiO(2) is not well
      understood. The photocatalytic elimination of Bacillus atrophaeus was examined
      under different calcination temperatures, dip-coating speeds, and ratios of
      TiO(2), SiO(2), and Ag to identify optimal production conditions for the
      production of TiO(2)- and/or TiO(2)/Ag-coated glass for surface disinfection.
      Photocatalytic disinfection of pure TiO(2) or TiO(2) plus Ag nanoparticles was
      dependent primarily on the calcination temperature. The antibacterial activity of
      TiO(2) films was optimal with a high dip-coating speed and high calcination
      temperature (600 degrees C). Maximal bacterial inactivation using TiO(2)/Ag
      coated glass was also observed following high-speed dip coating but with a low
      calcination temperature (250 degrees C). Scanning electron microscopy (SEM)
      showed that the Ag nanoparticles combined together at a high calcination
      temperature, leading to decreased antibacterial activity of TiO(2)/Ag films due
      to a smaller surface area of Ag nanoparticles. The presence of Ag enhanced the
      photocatalytic inactivation rate of TiO(2), producing a more pronounced effect
      with increasing levels of catalyst loading.

PMID- 21724886
TI  - Glycoside hydrolase activities of thermophilic bacterial consortia adapted to
      switchgrass.
AB  - Industrial-scale biofuel production requires robust enzymatic cocktails to
      produce fermentable sugars from lignocellulosic biomass. Thermophilic bacterial
      consortia are a potential source of cellulases and hemicellulases adapted to
      harsher reaction conditions than commercial fungal enzymes. Compost-derived
      microbial consortia were adapted to switchgrass at 60 degrees C to develop
      thermophilic biomass-degrading consortia for detailed studies. Microbial
      community analysis using small-subunit rRNA gene amplicon pyrosequencing and
      short-read metagenomic sequencing demonstrated that thermophilic adaptation to
      switchgrass resulted in low-diversity bacterial consortia with a high abundance
      of bacteria related to thermophilic paenibacilli, Rhodothermus marinus, and
      Thermus thermophilus. At lower abundance, thermophilic Chloroflexi and an
      uncultivated lineage of the Gemmatimonadetes phylum were observed. Supernatants
      isolated from these consortia had high levels of xylanase and endoglucanase
      activities. Compared to commercial enzyme preparations, the endoglucanase enzymes
      had a higher thermotolerance and were more stable in the presence of 1-ethyl-3
      methylimidazolium acetate ([C2mim][OAc]), an ionic liquid used for biomass
      pretreatment. The supernatants were used to saccharify [C2mim][OAc]-pretreated
      switchgrass at elevated temperatures (up to 80 degrees C), demonstrating that
      these consortia are an excellent source of enzymes for the development of
      enzymatic cocktails tailored to more extreme reaction conditions.

PMID- 21724888
TI  - Purification and characterization of the [NiFe]-hydrogenase of Shewanella
      oneidensis MR-1.
AB  - Shewanella oneidensis MR-1 possesses a periplasmic [NiFe]-hydrogenase (MR-1
      [NiFe]-H(2)ase) that has been implicated in H(2) production and oxidation as well
      as technetium [Tc(VII)] reduction. To characterize the roles of MR-1 [NiFe]
      H(2)ase in these proposed reactions, the genes encoding both subunits of MR-1
      [NiFe]-H(2)ase were cloned and then expressed in an MR-1 mutant without hyaB and
      hydA genes. Expression of recombinant MR-1 [NiFe]-H(2)ase in trans restored the
      mutant's ability to produce H(2) at 37% of that for the wild type. Following
      purification, MR-1 [NiFe]-H(2)ase coupled H(2) oxidation to reduction of
      Tc(VII)O(4)(-) and methyl viologen. Change of the buffers used affected MR-1
      [NiFe]-H(2)ase-mediated reduction of Tc(VII)O(4)(-) but not methyl viologen.
      Under the conditions tested, all Tc(VII)O(4)(-) used was reduced in Tris buffer,
      while in HEPES buffer, only 20% of Tc(VII)O(4)(-) was reduced. The reduced
      products were soluble in Tris buffer but insoluble in HEPES buffer. Transmission
      electron microscopy analysis revealed that Tc precipitates reduced in HEPES
      buffer were aggregates of crystallites with diameters of ~5 nm. Measurements with
      X-ray absorption near-edge spectroscopy revealed that the reduction products were
      a mixture of Tc(IV) and Tc(V) in Tris buffer but only Tc(IV) in HEPES buffer.
      Measurements with extended X-ray adsorption fine structure showed that while the
      Tc bonding environment in Tris buffer could not be determined, the Tc(IV) product
      in HEPES buffer was very similar to Tc(IV)O(2).nH(2)O, which was also the product
      of Tc(VII)O(4)(-) reduction by MR-1 cells. These results shows for the first time
      that MR-1 [NiFe]-H(2)ase catalyzes Tc(VII)O(4)(-) reduction directly by coupling
      to H(2) oxidation.

PMID- 21724889
TI  - High lytic infection rates but low abundances of prokaryote viruses in a humic
      lake (Vassiviere, Massif Central, France).
AB  - We explored the abundance and infection rates of viruses on a time series scale
      in the euphotic zone of the humic mesotrophic Lake Vassiviere (Massif Central,
      France) and compared them to nonhumic lakes of contrasting trophy (i.e., the
      oligomesotrophic Lake Pavin and the eutrophic Lake Aydat) located in the same
      geographical region and sampled during the same period. In Lake Vassiviere, the
      abundances of virus-like particles (range, 1.7 * 10(10) to 2.6 * 10(10) liter(
      1)) were significantly (P < 0.001) lower than in Lakes Pavin and Aydat. The
      percentage of virus-infected prokaryotic cells (mean, 18.0%) was significantly
      higher (P < 0.001) in Vassiviere than in Pavin (mean, 11.5%) and Aydat (mean,
      9.7%). In Vassiviere, the abundance of prokaryotes was a good predictor (r =
      0.78, P < 0.001) of the number of virus-like particles, while the potential
      grazing rate from heterotrophic nanoflagellates was positively correlated to the
      viral infection rate (r = 0.75, P < 0.001; n = 20), indicating the prevalence of
      cycling interactions among viruses, prokaryotes, and grazers, which is in
      agreement with past experiments. The absence of correlation between chlorophyll a
      concentrations (Chl) and viral parameters suggested that the resources for the
      lytic activity of viruses in Vassiviere were mainly under allochthonous control,
      through host activity. Indeed, compilation of data obtained from several nonhumic
      lakes in the French Massif Central revealed that Chl was positively correlated to
      the abundance of virus-like particles at concentrations above 0.5 MUg Chl liter(
      1) and negatively at concentrations below 0.5 MUg Chl liter(-1), suggesting that
      phytoplankton-derived resources could force prokaryotic growth to attain a
      certain threshold level when the host availability is sufficient to boost the
      proliferation of viruses. Therefore, based on the high level of lytic infection
      rates in Lake Vassiviere, we conclude that viruses are key agents for prokaryotic
      mortality and could influence the food web dynamics in humic lakes, which may
      ultimately depend on the internal cycling of resources and, perhaps, mainly on
      the allochthonous inputs and the associated humic substances.

PMID- 21724890
TI  - Soil microbial community successional patterns during forest ecosystem
      restoration.
AB  - Soil microbial community characterization is increasingly being used to determine
      the responses of soils to stress and disturbances and to assess ecosystem
      sustainability. However, there is little experimental evidence to indicate that
      predictable patterns in microbial community structure or composition occur during
      secondary succession or ecosystem restoration. This study utilized a
      chronosequence of developing jarrah (Eucalyptus marginata) forest ecosystems,
      rehabilitated after bauxite mining (up to 18 years old), to examine changes in
      soil bacterial and fungal community structures (by automated ribosomal intergenic
      spacer analysis [ARISA]) and changes in specific soil bacterial phyla by 16S rRNA
      gene microarray analysis. This study demonstrated that mining in these ecosystems
      significantly altered soil bacterial and fungal community structures. The
      hypothesis that the soil microbial community structures would become more similar
      to those of the surrounding nonmined forest with rehabilitation age was broadly
      supported by shifts in the bacterial but not the fungal community. Microarray
      analysis enabled the identification of clear successional trends in the bacterial
      community at the phylum level and supported the finding of an increase in
      similarity to nonmined forest soil with rehabilitation age. Changes in soil
      microbial community structure were significantly related to the size of the
      microbial biomass as well as numerous edaphic variables (including pH and C, N,
      and P nutrient concentrations). These findings suggest that soil bacterial
      community dynamics follow a pattern in developing ecosystems that may be
      predictable and can be conceptualized as providing an integrated assessment of
      numerous edaphic variables.

PMID- 21724891
TI  - Biosynthesis of a complex yersiniabactin-like natural product via the mic locus
      in phytopathogen Ralstonia solanacearum.
AB  - A genome mining study in the plant pathogenic bacterium Ralstonia solanacearum
      GMI1000 unveiled a polyketide synthase/nonribosomal peptide synthetase gene
      cluster putatively involved in siderophore biosynthesis. Insertional mutagenesis
      confirmed the respective locus to be operational under iron-deficient conditions
      and spurred the isolation of the associated natural product. Bioinformatic
      analyses of the gene cluster facilitated the structural characterization of this
      compound, which was subsequently identified as the antimycoplasma agent
      micacocidin. The metal-chelating properties of micacocidin were evaluated in
      competition experiments, and the cellular uptake of gallium-micacocidin complexes
      was demonstrated in R. solanacearum GMI1000, indicating a possible siderophore
      role. Comparative genomics revealed a conservation of the micacocidin gene
      cluster in defined, but globally dispersed phylotypes of R. solanacearum.

PMID- 21724892
TI  - Detection, isolation, and characterization of acidophilic methanotrophs from
      Sphagnum mosses.
AB  - Sphagnum peatlands are important ecosystems in the methane cycle. Methane
      oxidizing bacteria in these ecosystems serve as a methane filter and limit
      methane emissions. Yet little is known about the diversity and identity of the
      methanotrophs present in and on Sphagnum mosses of peatlands, and only a few
      isolates are known. The methanotrophic community in Sphagnum mosses, originating
      from a Dutch peat bog, was investigated using a pmoA microarray. A high
      biodiversity of both gamma- and alphaproteobacterial methanotrophs was found.
      With Sphagnum mosses as the inoculum, alpha- and gammaproteobacterial acidophilic
      methanotrophs were isolated using established and newly designed media. The 16S
      rRNA, pmoA, pxmA, and mmoX gene sequences showed that the alphaproteobacterial
      isolates belonged to the Methylocystis and Methylosinus genera. The Methylosinus
      species isolated are the first acid-tolerant members of this genus. Of the
      acidophilic gammaproteobacterial strains isolated, strain M5 was affiliated with
      the Methylomonas genus, and the other strain, M200, may represent a novel genus,
      most closely related to the genera Methylosoma and Methylovulum. So far, no
      acidophilic or acid-tolerant methanotrophs in the Gammaproteobacteria class are
      known. All strains showed the typical features of either type I or II
      methanotrophs and are, to the best of our knowledge, the first isolated
      (acidophilic or acid-tolerant) methanotrophs from Sphagnum mosses.

PMID- 21724893
TI  - Modification of norfloxacin by a Microbacterium sp. strain isolated from a
      wastewater treatment plant.
AB  - Antimicrobial residues found in municipal wastewater may increase selective
      pressure on microorganisms for development of resistance, but studies with mixed
      microbial cultures derived from wastewater have suggested that some bacteria are
      able to inactivate fluoroquinolones. Medium containing N-phenylpiperazine and
      inoculated with wastewater was used to enrich fluoroquinolone-modifying bacteria.
      One bacterial strain isolated from an enrichment culture was identified by 16S
      rRNA gene sequence analysis as a Microbacterium sp. similar to a plant growth
      promoting bacterium, Microbacterium azadirachtae (99.70%), and a nematode
      pathogen, "M. nematophilum" (99.02%). During growth in medium with norfloxacin,
      this strain produced four metabolites, which were identified by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance
      (NMR) analyses as 8-hydroxynorfloxacin, 6-defluoro-6-hydroxynorfloxacin,
      desethylene norfloxacin, and N-acetylnorfloxacin. The production of the first
      three metabolites was enhanced by ascorbic acid and nitrate, but it was inhibited
      by phosphate, amino acids, mannitol, formate, and thiourea. In contrast, N
      acetylnorfloxacin was most abundant in cultures supplemented with amino acids.
      This is the first report of defluorination and hydroxylation of a fluoroquinolone
      by an isolated bacterial strain. The results suggest that some bacteria may
      degrade fluoroquinolones in wastewater to metabolites with less antibacterial
      activity that could be subject to further degradation by other microorganisms.

PMID- 21724894
TI  - Characterization of an autoinducer of penicillin biosynthesis in Penicillium
      chrysogenum.
AB  - Filamentous fungi produce an impressive variety of secondary metabolites; many of
      them have important biological activities. The biosynthesis of these secondary
      metabolites is frequently induced by plant-derived external elicitors and appears
      to also be regulated by internal inducers, which may work in a way similar to
      that of bacterial autoinducers. The biosynthesis of penicillin in Penicillium
      chrysogenum is an excellent model for studying the molecular mechanisms of
      control of gene expression due to a good knowledge of the biochemistry and
      molecular genetics of beta-lactam antibiotics and to the availability of its
      genome sequence and proteome. In this work, we first developed a plate bioassay
      that allows direct testing of inducers of penicillin biosynthesis using single
      colonies of P. chrysogenum. Using this bioassay, we have found an inducer
      substance in the conditioned culture broths of P. chrysogenum and Acremonium
      chrysogenum. No inducing effect was exerted by gamma-butyrolactones, jasmonic
      acid, or the penicillin precursor delta-(L-alpha-aminoadipyl)-L-cysteinyl-D
      valine. The conditioned broth induced penicillin biosynthesis and transcription
      of the pcbAB, pcbC, and penDE genes when added at inoculation time, but its
      effect was smaller if added at 12 h and it had no effect when added at 24 h, as
      shown by Northern analysis and lacZ reporter studies. The inducer molecule was
      purified and identified by mass spectrometry (MS) and nuclear magnetic resonance
      (NMR) as 1,3-diaminopropane. Addition of pure 1,3-diaminopropane stimulated the
      production of penicillin by about 100% compared to results for the control
      cultures. Genes for the biosynthesis of 1,3-diaminopropane have been identified
      in the P. chrysogenum genome.

PMID- 21724895
TI  - Genomic and metabolic profiling of nonulosonic acids in Vibrionaceae reveal
      biochemical phenotypes of allelic divergence in Vibrio vulnificus.
AB  - Nonulosonic acids (NulOs) encompass a large group of structurally diverse nine
      carbon backbone alpha-keto sugars widely distributed among the three domains of
      life. Mammals express a specialized version of NulOs called sialic acids, which
      are displayed in prominent terminal positions of cell surface and secreted
      glycoconjugates. Within bacteria, the ability to synthesize NulOs has been
      demonstrated in a number of human pathogens and is phylogenetically widespread.
      Here we examine the distribution, diversity, evolution, and function of NulO
      biosynthesis pathways in members of the family Vibrionaceae. Among 27 species of
      Vibrionaceae examined at the genomic level, 12 species contained nab gene
      clusters. We document examples of duplication, divergence, horizontal transfer,
      and recombination of nab gene clusters in different Vibrionaceae lineages.
      Biochemical analyses, including mass spectrometry, confirmed that many species
      do, in fact, produce di-N-acetylated NulOs. A library of clinical and
      environmental isolates of Vibrio vulnificus served as a model for further
      investigation of nab allele genotypes and levels of NulO expression. The data
      show that lineage I isolates produce about 20-fold higher levels of NulOs than
      lineage II isolates. Moreover, nab gene alleles found in a subset of V.
      vulnificus clinical isolates express 40-fold higher levels of NulOs than nab
      alleles associated with environmental isolates. Taken together, the data
      implicate the family Vibrionaceae as a "hot spot" of NulO evolution and suggest
      that these molecules may have diverse roles in environmental persistence and/or
      animal virulence.

PMID- 21724896
TI  - Mapping the substrate binding site of phenylacetone monooxygenase from
      Thermobifida fusca by mutational analysis.
AB  - Baeyer-Villiger monooxygenases catalyze oxidations that are of interest for
      biocatalytic applications. Among these enzymes, phenylacetone monooxygenase
      (PAMO) from Thermobifida fusca is the only protein showing remarkable stability.
      While related enzymes often present a broad substrate scope, PAMO accepts only a
      limited number of substrates. Due to the absence of a substrate in the elucidated
      crystal structure of PAMO, the substrate binding site of this protein has not yet
      been defined. In this study, a structural model of cyclopentanone monooxygenase,
      which acts on a broad range of compounds, has been prepared and compared with the
      structure of PAMO. This revealed 15 amino acid positions in the active site of
      PAMO that may account for its relatively narrow substrate specificity. We
      designed and analyzed 30 single and multiple mutants in order to verify the role
      of these positions. Extensive substrate screening revealed several mutants that
      displayed increased activity and altered regio- or enantioselectivity in Baeyer
      Villiger reactions and sulfoxidations. Further substrate profiling resulted in
      the identification of mutants with improved catalytic properties toward
      synthetically attractive compounds. Moreover, the thermostability of the mutants
      was not compromised in comparison to that of the wild-type enzyme. Our data
      demonstrate that the positions identified within the active site of PAMO, namely,
      V54, I67, Q152, and A435, contribute to the substrate specificity of this enzyme.
      These findings will aid in more dedicated and effective redesign of PAMO and
      related monooxygenases toward an expanded substrate scope.

PMID- 21724897
TI  - Microbial utilization and selectivity of pectin fractions with various
      structures.
AB  - To evaluate the fermentation properties of oligosaccharides derived from pectins
      and their parent polysaccharides, a 5-ml-working-volume, pH- and temperature
      controlled fermentor was tested. Six pectic oligosaccharides representing
      specific substructures found within pectins were prepared. These consisted of
      oligogalacturonides (average degrees of polymerization [DP] of 5 and 9),
      methylated oligogalacturonides (average DP of 5), oligorhamnogalacturonides
      (average DP of 10 as a disaccharide unit of galacturonic acid and rhamnose),
      oligogalactosides (average DP of 5), and oligoarabinosides (average DP of 6). The
      influence of these carbohydrates on the human fecal microbiota was evaluated. Use
      of neutral sugar fractions resulted in an increase in Bifidobacterium populations
      and gave higher organic acid yields. The Bacteroides-Prevotella group
      significantly increased on all oligosaccharides except oligogalacturonides with
      an average DP of 5. The most selective substrates for bifidobacteria were
      arabinan, galactan, oligoarabinosides, and oligogalactosides.

PMID- 21724898
TI  - Characterization of methicillin-resistant Staphylococcus aureus isolates from
      food and food products of poultry origin in Germany.
AB  - During a survey of fresh chicken and turkey meat as well as chicken and turkey
      meat products for the presence of methicillin-resistant Staphylococcus aureus
      (MRSA) isolates in Germany, 32 (37.2%) of 86 samples were MRSA positive. Twenty
      eight of these MRSA isolates belonged to clonal complex 398 (CC398), which is
      widespread among food-producing animals. These CC398 isolates carried SCCmec
      elements of type IV or V and exhibited spa type t011, t034, t899, t2346 or t6574
      and either the known dru types dt2b, dt6j, dt10a, dt10q, dt11a, dt11v, and dt11ab
      or the novel dru types dt6m, dt10as, and dt10at. In addition, two MRSA sequence
      type 9 (ST9) isolates with a type IV SCCmec cassette, spa type t1430, and dru
      type dt10a as well as single MRSA ST5 and ST1791 isolates with a type III SCCmec
      cassette, spa type t002, and dru type dt9v were identified. All but two isolates
      were classified as multiresistant. A wide variety of resistance phenotypes and
      genotypes were detected. All isolates were negative for the major virulence
      factors, such as Panton-Valentine leukocidin, toxic shock syndrome toxin 1, or
      exfoliative toxins. In contrast to the MRSA CC398 isolates, the four ST9, ST5, or
      ST1791 isolates harbored the egc gene cluster for enterotoxin G, I, M, N, O, and
      U genes. Although the relevance of contamination of fresh poultry meat or poultry
      products with MRSA is currently unclear, the presence of multiresistant and, in
      part, enterotoxigenic MRSA emphasizes the need for further studies to elucidate
      possible health hazards for consumers.

PMID- 21724899
TI  - Prevalence and genotypic characteristics of Clostridium difficile in a closed and
      integrated human and swine population.
AB  - Recently, an apparent rise in the number of cases attributed to community
      acquired Clostridium difficile infection has led researchers to explore
      additional sources of infection. The finding of C. difficile in food animals and
      retail meat has raised concern about potential food-borne and occupational
      exposures. The objective of this study was to compare C. difficile isolated from
      a closed population of healthy individuals consisting of both humans and swine in
      order to investigate possible food safety and occupational risks for exposure.
      Using a multistep enrichment isolation technique, we identified 11.8% of the
      human wastewater samples and 8.6% of the swine samples that were positive for C.
      difficile. The prevalences of C. difficile in swine production groups differed
      significantly (P < 0.05); however, the prevalences in the two human occupational
      group cohorts did not differ significantly (P = 0.81). The majority of the human
      and swine isolates were similar based on multiple typing methods. The similarity
      in C. difficile prevalence in the human group cohorts suggests a low occupational
      hazard, while a greatly decreased prevalence of C. difficile in later-stage swine
      production groups suggests a diminished risk for food-borne exposure. The
      similarity of strains in the two host species suggests the possibility of a
      common environmental source for healthy individuals in a community setting.

PMID- 21724900
TI  - Ethics for the pediatrician: caring for abused children.

PMID- 21724902
TI  - Normal pubertal development: part II: clinical aspects of puberty.

PMID- 21724901
TI  - Breastfeeding: more than just good nutrition.

PMID- 21724903
TI  - Focus on diagnosis: the D-test.

PMID- 21724905
TI  - Research and statistics: likelihood ratio in diagnosis.

PMID- 21724906
TI  - Index of suspicion: case 1: leg cramps, hand spasms, diarrhea, and substantial
      weight loss in a 12 year old: case 2: hypothermia, hypoglycemia, and
      hyperbilirubinemia in a neonate: case 3: recurrent fevers, abdominal pain, and
      cervical lymphadenopathy in a 7 year old.

PMID- 21724907
TI  - Tumor markers in infancy and childhood.

PMID- 21724908
TI  - Pheochromocytoma.

PMID- 21724909
TI  - Associations of physical activity and television viewing time with retinal
      vascular caliber in a multiethnic Asian population.
AB  - PURPOSE. The aim of this study was to examine the relationship of physical
      activity and television (TV) viewing time with retinal vascular caliber in a
      multiethnic Asian population. METHODS. Chinese, Indian, and Malay participants (n
      = 3866) were examined cross-sectionally in the Singapore Prospective Study
      Program (2004-2007). Leisure-time physical activity and TV viewing time were
      assessed by the use of an interviewer-administered questionnaire. Retinal
      arteriolar and venular calibers were measured from digital retinal photographs.
      RESULTS. After adjusting for demographic, behavioral, and medical factors, those
      in the lowest quartile of leisure-time physical activity had a wider venular
      caliber (by 1.51 MUm; 95% confidence interval [CI], 0.01-2.92) compared with
      those in the highest quartile. Using sex- and ethnicity-specific quartiles,
      stronger associations were noted in males (2.23 MUm; 95% CI, 0.10-4.38) and
      Chinese (2.52 MUm; 95% CI, 0.44-4.59) participants. Females who watched >2 hours
      of TV per day had a narrow arteriolar caliber (by 1.28 MUm; 95% CI, -2.56--0.03),
      compared with the arteriolar caliber of those who watched less TV. CONCLUSIONS.
      Lower physical activity and higher TV viewing time (in females) were adversely
      associated with retinal microvascular caliber among Asian adults. Additional
      cross-sectional and longitudinal studies are needed to further clarify the
      potential mediating role of the microvasculature in the relationship between
      these behavioral risk factors and poor cardiometabolic health outcomes.

PMID- 21724910
TI  - Ceramide-1-phosphate, a new mediator of development and survival in retina
      photoreceptors.
AB  - PURPOSE. Simple sphingolipids control crucial cellular processes in several cell
      types. Previous work demonstrated that sphingolipids, such as ceramide,
      sphingosine, and sphingosine-1-phosphate, are key mediators in the regulation of
      survival, differentiation, and proliferation of retina photoreceptors. Ceramide-1
      phosphate (C1P) regulates growth and survival in several cell types; however,
      little is known concerning its functions in the retina. Whether C1P also
      participates in controlling photoreceptor development was also explored. METHODS.
      Rat retina neuronal cultures were supplemented with 1 to 10 MUM C1P.
      Proliferation was determined by evaluating 5-bromo-2-deoxyuridine (BrdU) uptake
      and the number of mitotic figures and differentiation by evaluating opsin and
      peripherin expression by immunocytochemistry and Western blot. Apoptosis was
      inhibited with the pan caspase inhibitor ZVADFMK and evaluated by TUNEL assay,
      propidium iodide/annexin V, and DAPI labeling. Preservation of mitochondrial
      membrane potential was evaluated. RESULTS. C1P enhanced BrdU uptake and increased
      mitosis in retinal progenitors. C1P addition advanced photoreceptor
      differentiation, enhancing opsin and peripherin expression and stimulating
      development of the apical processes in which these proteins were concentrated. In
      the absence of these trophic factors, photoreceptors degenerated after 4 days in
      vitro, and at day 6, almost 50% of photoreceptors were apoptotic. C1P decreased
      photoreceptor apoptosis, reducing this percentage by half. Inhibiting caspase
      activity reduced photoreceptor apoptosis in the controls, but did not increase
      opsin expression, implying that C1P has separate effects on differentiation and
      survival. CONCLUSIONS. These results suggest for the first time that C1P is a
      novel mediator that has multiple functions in photoreceptors, initially
      regulating their proliferation and then promoting their survival and
      differentiation.

PMID- 21724911
TI  - Variation of cone photoreceptor packing density with retinal eccentricity and
      age.
AB  - PURPOSE: To study the variation of cone photoreceptor packing density across the
      retina in healthy subjects of different ages. METHODS: High-resolution adaptive
      optics scanning laser ophthalmoscope (AOSLO) systems were used to systematically
      image the retinas of two groups of subjects of different ages. Ten younger
      subjects (age range, 22-35 years) and 10 older subjects (age range, 50-65 years)
      were tested. Strips of cone photoreceptors, approximately 12 degrees  * 1.8
      degrees  long were imaged for each of the four primary retinal meridians:
      superior, inferior, nasal, and temporal. Cone photoreceptors within the strips
      were counted, and cone photoreceptor packing density was calculated. Statistical
      analysis (three-way ANOVA) was used to calculate the interaction for cone
      photoreceptor packing density between age, meridian, and eccentricity. RESULTS:
      As expected, cone photoreceptor packing density was higher close to the fovea and
      decreased with increasing retinal eccentricity from 0.18 to 3.5 mm (~0.6-12
      degrees ). Older subjects had approximately 75% of the cone density at 0.18 mm
      (~0.6 degrees ), and this difference decreased rapidly with eccentricity, with
      the two groups having similar cone photoreceptor packing densities beyond 0.5 mm
      retinal eccentricity on average. CONCLUSIONS: Cone packing density in the living
      human retina decreases as a function of age within the foveal center with the
      largest difference being found at our most central measurement site. At all ages,
      the retina showed meridional difference in cone densities, with cone
      photoreceptor packing density decreasing faster with increasing eccentricity in
      the vertical dimensions than in the horizontal dimensions.

PMID- 21724912
TI  - The contribution of the posterior surface to the corneal aberrations in eyes
      after keratoplasty.
AB  - PURPOSE: To investigate the contribution of posterior corneal surfaces to higher
      order aberrations (HOAs) of the cornea, optical quality, and visual acuity after
      keratoplasty. METHODS: Corneal topography of anterior and posterior surfaces and
      pachymetry were conducted using anterior segment optical coherence tomography (AS
      OCT) in 40 eyes (10 eyes after penetrating keratoplasty [PK], 10 eyes after deep
      anterior lamellar keratoplasty [DALK], 10 eyes after Descemet's stripping
      automated endothelial keratoplasty [DSAEK], and 10 normal eyes). Anterior,
      posterior, and total corneal HOAs were calculated using ray-tracing and
      decomposition into Zernike polynomials and were evaluated as root mean square
      values. Modulation transfer functions (MTFs) were also evaluated. RESULTS:
      Topography maps of the anterior and posterior surfaces showed reverse patterns in
      the normal, PK, and DALK eyes, but not in DSAEK eyes. In the normal, PK, and DALK
      eyes, the total corneal HOAs were significantly smaller (~10%) than were the HOAs
      of the anterior surface (P < 0.01), whereas there was no significant difference
      between total and anterior HOAs in the DSAEK eyes (P = 0.483). In the normal, PK,
      and DALK eyes, the MTFs of the total cornea were slightly better than those of
      the anterior surface. In the DSAEK eyes, the MTFs of the total cornea were lower
      than those of the anterior surface. Visual acuity was significantly correlated
      with total and anterior surface HOAs (P < 0.05). CONCLUSIONS: Posterior surfaces
      compensate for anterior aberrations in normal, PK, and DALK eyes. In DSAEK eyes,
      the posterior surface increased total corneal HOAs and had a negative influence
      on MTFs.

PMID- 21724913
TI  - Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and
      dexamethasone in the healthy and inflamed retina.
AB  - PURPOSE: Glucocorticoids are used to treat macular edema, although the mechanisms
      underlying this effect remain largely unknown. The authors have evaluated in the
      normal and endotoxin-induced uveitis (EIU) rats, the effects of dexamethasone
      (dex) and triamcinolone acetonide (TA) on potassium channel Kir4.1 and aquaporin
      4 (AQP4), the two main retinal Muller glial (RMG) channels controlling retinal
      fluid movement. METHODS: Clinical as well as relatively low doses of dex and TA
      were injected in the vitreous of normal rats to evaluate their influence on
      Kir4.1 and AQP4 expression 24 hours later. The dose-dependent effects of the two
      glucocorticoids were investigated using rat neuroretinal organotypic cultures.
      EIU was induced by footpad lipopolysaccharide injection, without or with 100 nM
      intraocular dex or TA. Glucocorticoid receptor and channel expression levels were
      measured by quantitative PCR, Western blot, and immunohistochemistry. RESULTS:
      The authors found that dex and TA exert distinct and specific channel regulations
      at 24 hours after intravitreous injection. Dex selectively upregulated Kir4.1
      (not AQP4) in healthy and inflamed retinas, whereas TA induced AQP4 (not Kir4.1)
      downregulation in normal retina and upregulation in EIU. The lower concentration
      (100 nM) efficiently regulated the channels. Moreover, in EIU, an inflammatory
      condition, the glucocorticoid receptor was downregulated in the retina, which was
      prevented by intravitreous injections of the low concentration of dex or TA.
      CONCLUSIONS: The results show that dex and TA are far from being equivalent to
      modulate RMG channels. Furthermore, the authors suggest that low doses of
      glucocorticoids may have antiedematous effects on the retina with reduced
      toxicity.

PMID- 21724914
TI  - The role of Bcl-xL in mouse RPE cell survival.
AB  - PURPOSE. Retinal pigment epithelial (RPE) cell survival plays a critical role in
      normal physiology and in retinal diseases, such as age-related macular
      degeneration (AMD) and proliferative vitreoretinopathy (PVR). We have previously
      demonstrated that Bcl-x(L) is an important cell survival protein in human RPE
      (hRPE) cells. Herein, we determined the role of Bcl-x(L) as a survival protein in
      mouse RPE (mRPE) cells. METHODS. Survival factor gene expression and Bcl-x(L)
      protein distribution were determined using qRT-PCR and immunohistochemistry,
      respectively. Cultured mRPE cells were transfected with two modified 2'-O
      methoxyethoxy antisense oligonucleotides (ASOs): Bcl-x(L)-mismatched control and
      Bcl-x(L)-specific. Bcl-x(L) protein levels were analyzed using Western blot. To
      determine the effects of survival factor regulation in mRPE cells, cultured cells
      were treated for 24 hours with mouse TNF-alpha, human IL-1beta, and human TNF
      alpha. RESULTS. Bcl-x(L) was the most highly expressed survival factor in both
      mouse eyecup and cultured mRPE cells, whereas Bax was the most highly expressed
      antisurvival factor. Bcl-x(L) was expressed in the RPE layer, and the
      distribution among the retinal layers was similar to that observed in human
      eyecups. IL-1beta and TNF-alpha had minimal effect on Bcl-x(L) and Bax expression
      and strongly upregulated Traf-1. Transfection with Bcl-x(L)-specific ASO resulted
      in markedly diminished Bcl-x(L) gene expression, Bcl-x(L) protein levels, and
      cell number. CONCLUSIONS. Bcl-x(L) is the most highly expressed survival gene in
      mRPE cells and is essential for mRPE cell survival. Our data suggest that mouse
      tissue is an appropriate model for investigations of RPE survival factor genes.

PMID- 21724915
TI  - The role of nonenzymatic glycation and carbonyls in collagen cross-linking for
      the treatment of keratoconus.
AB  - PURPOSE: Corneal cross-linking (CXL) is a treatment for keratoconus that
      eliminates the need for keratoplasty in most patients. However, its molecular
      mechanisms remain under study. Advanced glycation end products (AGEs) have been
      suggested by many studies as the causative strengthening agent during CXL, though
      no studies to date have directly tested this hypothesis. METHODS: Corneas of
      young rabbits and sharks were pretreated with pyridoxal hydrochloride and copper
      ions before CXL. Two known inhibitors of AGE formation, aminoguanidine and
      rifampicin, were applied during CXL in the treatment solution. Tensile strength
      tests were conducted after these experiments to detect diminished or accentuated
      corneal stiffening after CXL. SDS-PAGE was performed on type I collagen cross
      linked in the absence and presence of AGE inhibitors. RESULTS: Pretreatment with
      pyridoxal hydrochloride resulted in significantly higher corneal stiffening after
      CXL. AGE inhibitors significantly diminished cross-linking as detected by both
      tensile strength measurements using whole corneas and gel electrophoresis of in
      vitro cross-linking of type I collagen in solution, in the presence and absence
      of the inhibitors. Rifampicin inhibited CXL more significantly than
      aminoguanidine in gel electrophoresis and tensile strength tests, confirming
      recent findings on its efficacy as an AGE inhibitor. CONCLUSIONS: Data presented
      here suggest that CXL is carbonyl dependent and involves the formation of AGE
      cross-links. Six possible cross-linking mechanisms are discussed.

PMID- 21724916
TI  - Consumption of DHA + EPA by low-income women during pregnancy and lactation.
AB  - BACKGROUND: The omega-3-fatty acid docosahexaenoic acid (DHA) is important in
      infant brain development and maturation. The advisable intake of the omega-3
      fatty acids DHA and eicosapentaenoic acid (EPA) for pregnant and lactating women
      is 300 mg/d or 9 g/month. The objective of this cross-sectional study was to test
      the hypothesis that low-income pregnant/or lactating women do not consume
      advisable amounts of DHA+EPA and to determine whether any of the measured
      demographic factors were related to DHA and EPA consumption. METHODS: This study
      was conducted September 2007 to March 2008 and used the N-3 Fatty Acid Food
      Frequency Questionnaire for dietary assessment in a convenience sample of women
      (N = 68) enrolled in a local maternal infant health program. Women who reported
      fish or seafood allergies were excluded. The monthly consumption of DHA+EPA from
      food sources was measured, and participant race, ethnicity, country of origin,
      primary language, level of education, marital status, intake of prenatal vitamins
      containing DHA+EPA, and warnings of fish toxicity were assessed. The data were
      analyzed using 1-way analysis of variance and t tests. RESULTS: The average
      reported DHA+EPA intake was 1.18 g/month across all race/ethnicities. African
      Americans consumed significantly more DHA+EPA, 2.79 g/month, compared with
      Hispanics (1.64 g) and Caucasians (0.93 g). United States natives consumed
      significantly more DHA+EPA than immigrants (2.45 g vs 1.55 g). CONCLUSIONS: Low
      income pregnant/and lactating women in the study consumed less than the advisable
      amounts of DHA+EPA. Both ethnicity and country of origin are related to DHA+EPA
      intake.

PMID- 21724917
TI  - Abductor tendon tears of the hip: evaluation and management.
AB  - The gluteus medius and minimus muscle-tendon complex is crucial for gait and
      stability in the hip joint. There are three clinical presentations of abductor
      tendon tears. Degenerative or traumatic tears of the hip abductor tendons, so
      called rotator cuff tears of the hip, are seen in older patients with intractable
      lateral hip pain and weakness but without arthritis of the hip joint. The second
      type of tear may be relatively asymptomatic. It is often seen in patients
      undergoing arthroplasty for femoral neck fracture or elective total hip
      arthroplasty (THA) for osteoarthritis. The third type of abductor tendon
      dysfunction occurs with avulsion or failure of repair following THA performed
      through the anterolateral approach. Abductor tendon tear should be confirmed on
      MRI. When nonsurgical management is unsuccessful, open repair of the tendons with
      transosseous sutures is recommended. Good pain relief has been reported following
      endoscopic repair. Abductor tendon repair has had inconsistent results in persons
      with avulsion following THA. Reconstruction with a gluteus maximus muscle flap or
      Achilles tendon allograft has provided promising short-term results in small
      series.

PMID- 21724918
TI  - Management of distal clavicle fractures.
AB  - Most clavicle fractures heal without difficulty. However, radiographic nonunion
      after distal clavicle fracture has been reported in 10% to 44% of patients. Type
      II distal clavicle fractures, which involve displacement, are associated with the
      highest incidence of nonunion. Several studies have questioned the clinical
      relevance of distal clavicle nonunion, however. Nonsurgical and surgical
      management provide similar results. The decision whether to operate may be
      influenced by the amount of fracture displacement and the individual demands of
      the patient. Surgical options to achieve bony union include transacromial wire
      fixation, a modified Weaver-Dunn procedure, use of a tension band, screw
      fixation, plating, and arthroscopy. Each technique has advantages and
      disadvantages; insufficient evidence exists to demonstrate that any one technique
      consistently provides the best results.

PMID- 21724919
TI  - Fall prevention in the elderly: analysis and comprehensive review of methods used
      in the hospital and in the home.
AB  - Falls in the elderly are a significant problem both in and out of the hospital.
      The Deficit Reduction Act of 2005 and the Fiscal Year 2009 Inpatient Prospective
      Payment System Final Rule, as outlined by the Centers for Medicare & Medicaid
      Services, placed on hospitals the financial burden of fall prevention for falls
      (ie, hospital-acquired conditions) that could have been prevented by following
      evidence-based guidelines. Multifaceted and individualized programs have been
      created to prevent falls in the elderly. Many of these interventions are based on
      expert opinion and statistical trends. Our review of the literature revealed that
      the risk of fall is only slightly greater in the hospital environment than in the
      home and that there is no medical evidence that evidence-based guidelines are
      effective in fall prevention.

PMID- 21724920
TI  - Multiple myeloma: diagnosis and orthopaedic implications.
AB  - Multiple myeloma is a hematologic malignancy that commonly affects the skeletal
      system. The disease is primarily managed medically with chemotherapeutic agents.
      Pathologic fractures are common in patients with diagnosed and undiagnosed
      disease. The number of patients diagnosed with multiple myeloma is increasing, as
      is the incidence of associated pathologic fractures. Novel chemotherapeutic
      agents and radiation therapy protocols have been used to extend the average life
      span of patients with this disease. Various methods that allow for restoration of
      function and pain reduction can be used to stabilize and manage fractures
      associated with multiple myeloma. The orthopaedic surgeon and oncology team must
      work together to develop an individualized treatment plan to improve patient
      quality of life and provide pain relief.

PMID- 21724921
TI  - Advances in magnetic resonance imaging of articular cartilage.
AB  - The pathology, assessment, and management of articular cartilage lesions of the
      hip and knee have been the subject of considerable attention in the recent
      orthopaedic literature. MRI has long been an important tool in the diagnosis and
      management of articular cartilage pathology, but detecting and interpreting early
      cartilaginous degeneration with this technology has been difficult. Biochemical
      based MRI has been advocated to detect early cartilaginous degenerative changes
      and assess cartilage repair. Techniques such as T2 mapping, T1rho (ie, T1 in the
      rotating frame), sodium MRI, and delayed gadolinium-enhanced MRI of cartilage
      (dGEMRIC) take advantage of changes in the complex biochemical composition of
      articular cartilage and may help detect morphologic cartilaginous changes earlier
      than does conventional MRI. Although the newer modalities have been used
      primarily in the research setting, their ability to assess the microstructure of
      articular cartilage may eventually enhance the diagnosis and management of
      osteoarthritis.

PMID- 21724922
TI  - Surgical exposures of the radius and ulna.
AB  - The forearm contains many muscles, nerves, and vascular structures that change
      position on forearm rotation. Exposure of the radial shaft is best achieved with
      the Henry (volar) or Thompson (dorsal) approach. The volar flexor carpi radialis
      approaches are used increasingly for exposure of the distal radius. Although the
      dorsal approach is a safe utilitarian option with many applications, its use for
      managing fracture of the distal radius has waned. Potential complications
      associated with radial exposure include injury to the superficial branch of the
      radial nerve, the lateral antebrachial cutaneous nerve, and the cephalic vein.
      Dorsal and ulnar proximal radial exposures are associated with increased risk of
      injury to the posterior interosseous nerve. With surgical exposure of the ulna,
      care is required to avoid injuring the dorsal cutaneous branch of the ulnar
      nerve.

PMID- 21724923
TI  - Complications in reverse total shoulder arthroplasty.
AB  - Reverse total shoulder arthroplasty was initially used to manage complex shoulder
      problems. Indications have been expanded to include rotator cuff arthropathy,
      massive rotator cuff tear, failed shoulder arthroplasty, and fracture sequelae.
      Increased use of primary reverse total shoulder arthroplasty has led to reports
      of associated problems unique to the procedure. The most common complications
      include neurologic injury, periprosthetic fracture, hematoma, infection, scapular
      notching, dislocation, mechanical baseplate failure, and acromial fracture.
      Little information has been published regarding best practices for managing these
      complications.

PMID- 21724924
TI  - Biologic repair and regeneration of the intervertebral disk.

PMID- 21724925
TI  - When good drugs turn weirdly bad.

PMID- 21724926
TI  - Update in hospital medicine: studies likely to affect inpatient practice in 2011.
AB  - Dabigatran (Pradaxa) will likely start to replace warfarin (Coumadin) both to
      prevent stroke in patients with atrial fibrillation and to prevent recurrent
      venous thromboembolism. Using a checklist during insertion of central venous
      catheters can decrease the rate of catheter-related bloodstream infections in the
      intensive care unit. The overall survival rate of patients who undergo
      cardiopulmonary resuscitation in the intensive care unit is approximately 16%;
      the rate is lower in patients who are receiving pressor drugs and higher in those
      with ventricular tachycardia or ventricular fibrillation. Patients lacking follow
      up with a primary care physician within 30 days of discharge are at high risk of
      readmission and have a trend for longer length of hospital stay. Preoperative
      stress testing for patients undergoing noncardiac surgery should be done
      selectively, i.e., in patients at high risk.

PMID- 21724927
TI  - Hypothermia after cardiac arrest: beneficial, but slow to be adopted.
AB  - Survivors of cardiac arrest due to ventricular tachycardia or ventricular
      fibrillation have improved neurologic outcomes if they are cooled to a core body
      temperature of 32 degrees C to 34 degrees C for 24 hours as soon as possible
      after reaching the hospital.

PMID- 21724928
TI  - Managing cancer pain: frequently asked questions.
AB  - For a variety of reasons, cancer pain is often undertreated, adversely affecting
      the quality of life for patients and caregivers. To manage cancer pain
      effectively, physicians need to understand its pathogenesis, how to assess it,
      how to treat it, and, in particular, how to optimize opioid treatment. We discuss
      common questions faced by physicians in everyday practice.

PMID- 21724929
TI  - Vancomycin: a 50-something-year-old antibiotic we still don't understand.
AB  - Because a significant proportion of Staphylococcus aureus strains as well as most
      coagulase-negative staphylococci are resistant to penicillin and semisynthetic
      beta-lactam drugs, the need for vancomycin and related antibiotics has never been
      greater. Effective use of vancomycin requires knowledge of dosing parameters and
      selection of target trough levels appropriate to the specific infection and to
      the pathogen being treated. For clinicians, it is vital to remain up-to-date with
      evolving definitions for vancomycin susceptibility, with new interpretations of
      efficacy, and with information on toxicity.

PMID- 21724930
TI  - Rash from hepatitis C treatment.

PMID- 21724931
TI  - Bronchial thermoplasty: a promising therapy, still in its infancy.

PMID- 21724932
TI  - Bronchial thermoplasty: a new treatment for severe refractory asthma.
AB  - Bronchial thermoplasty was recently approved for treating severe refractory
      asthma that is not well controlled by high-dose inhaled corticosteroids and long
      acting bronchodilator therapy. This article reviews its indications, evidence of
      efficacy, and protocols.

PMID- 21724933
TI  - Systems antecedents for dissemination and implementation: a review and analysis
      of measures.
AB  - There is a growing emphasis on the role of organizations as settings for
      dissemination and implementation. Only recently has the field begun to consider
      features of organizations that affect dissemination and implementation of
      evidence-based interventions. This manuscript identifies and evaluates available
      measures for five key organizational-level constructs: (a) leadership, (b)
      vision, (c) managerial relations, (d) climate, and (e) absorptive capacity.
      Overall the picture was the same across the five constructs--no measure was used
      in more than one study, many studies did not report the psychometric properties
      of the measures, some assessments were based on a single response per unit, and
      the level of the instrument and analysis did not always match. One must seriously
      consider the development and evaluation of a robust set of measures that will
      serve as the basis of building the field, allow for comparisons across
      organizational types and intervention topics, and allow a robust area of
      dissemination and implementation research to develop.

PMID- 21724934
TI  - RNA interference in fungi: pathways, functions, and applications.
AB  - Small RNA molecules of about 20 to 30 nucleotides function in gene regulation and
      genomic defense via conserved eukaryotic RNA interference (RNAi)-related
      pathways. The RNAi machinery consists of three core components: Dicer, Argonaute,
      and RNA-dependent RNA polymerase. In fungi, the RNAi-related pathways have three
      major functions: genomic defense, heterochromatin formation, and gene regulation.
      Studies of Schizosaccharomyces pombe and Neurospora, and other fungi have
      uncovered surprisingly diverse small RNA biogenesis pathways, suggesting that
      fungi utilize RNAi-related pathways in various cellular processes to adapt to
      different environmental conditions. These studies also provided important
      insights into how RNAi functions in eukaryotic systems in general. In this
      review, we will discuss our current understanding of the fungal RNAi-related
      pathways and their functions, with a focus on filamentous fungi. We will also
      discuss how RNAi can be used as a tool in fungal research.

PMID- 21724935
TI  - A genomewide screen for tolerance to cationic drugs reveals genes important for
      potassium homeostasis in Saccharomyces cerevisiae.
AB  - Potassium homeostasis is crucial for living cells. In the yeast Saccharomyces
      cerevisiae, the uptake of potassium is driven by the electrochemical gradient
      generated by the Pma1 H(+)-ATPase, and this process represents a major consumer
      of the gradient. We considered that any mutation resulting in an alteration of
      the electrochemical gradient could give rise to anomalous sensitivity to any
      cationic drug independently of its toxicity mechanism. Here, we describe a
      genomewide screen for mutants that present altered tolerance to hygromycin B,
      spermine, and tetramethylammonium. Two hundred twenty-six mutant strains
      displayed altered tolerance to all three drugs (202 hypersensitive and 24
      hypertolerant), and more than 50% presented a strong or moderate growth defect at
      a limiting potassium concentration (1 mM). Functional groups such as protein
      kinases and phosphatases, intracellular trafficking, transcription, or cell cycle
      and DNA processing were enriched. Essentially, our screen has identified a
      substantial number of genes that were not previously described to play a direct
      or indirect role in potassium homeostasis. A subset of 27 representative mutants
      were selected and subjected to diverse biochemical tests that, in some cases,
      allowed us to postulate the basis for the observed phenotypes.

PMID- 21724936
TI  - Global transcriptome changes underlying colony growth in the opportunistic human
      pathogen Aspergillus fumigatus.
AB  - Aspergillus fumigatus is the most common and deadly pulmonary fungal infection
      worldwide. In the lung, the fungus usually forms a dense colony of filaments
      embedded in a polymeric extracellular matrix. To identify candidate genes
      involved in this biofilm (BF) growth, we used RNA-Seq to compare the
      transcriptomes of BF and liquid plankton (PL) growth. Sequencing and mapping of
      tens of millions sequence reads against the A. fumigatus transcriptome identified
      3,728 differentially regulated genes in the two conditions. Although many of
      these genes, including the ones coding for transcription factors, stress
      response, the ribosome, and the translation machinery, likely reflect the
      different growth demands in the two conditions, our experiment also identified
      hundreds of candidate genes for the observed differences in morphology and
      pathobiology between BF and PL. We found an overrepresentation of upregulated
      genes in transport, secondary metabolism, and cell wall and surface functions.
      Furthermore, upregulated genes showed significant spatial structure across the A.
      fumigatus genome; they were more likely to occur in subtelomeric regions and
      colocalized in 27 genomic neighborhoods, many of which overlapped with known or
      candidate secondary metabolism gene clusters. We also identified 1,164 genes that
      were downregulated. This gene set was not spatially structured across the genome
      and was overrepresented in genes participating in primary metabolic functions,
      including carbon and amino acid metabolism. These results add valuable insight
      into the genetics of biofilm formation in A. fumigatus and other filamentous
      fungi and identify many relevant, in the context of biofilm biology, candidate
      genes for downstream functional experiments.

PMID- 21724937
TI  - Calcineurin colocalizes with P-bodies and stress granules during thermal stress
      in Cryptococcus neoformans.
AB  - Calcineurin is a calcium-calmodulin-activated serine/threonine-specific
      phosphatase that operates during cellular responses to stress and plays a
      prominent role in transcriptional control, whereas regulatory events beyond
      transcription are less well characterized. This study reveals a novel
      transcription-independent role of calcineurin during the temperature stress
      response in the human fungal pathogen Cryptococcus neoformans. The diffusely
      cytoplasmic calcineurin catalytic subunit Cna1 relocates to endoplasmic reticulum
      (ER)-associated puncta and the mother-bud neck when cells are subjected to 37
      degrees C. More than 50% of Cna1 puncta contain the P-body constituent decapping
      enzyme Dcp1 and the stress granule constituent poly(A)-binding protein Pub1.
      These results support a model in which calcineurin orchestrates thermal stress
      responses by associating with sites of mRNA processing.

PMID- 21724938
TI  - Effects of maternal selenium supply and plane of nutrition during gestation on
      passive transfer of immunity and health in neonatal lambs.
AB  - To investigate the influence of maternal Se supply and plane of nutrition on lamb
      morbidity, mortality, and passive transfer of IgG, pregnant ewe lambs were used
      in 2 experiments with 2 * 3 factorial treatment arrangements. Supplementation of
      Se began at breeding and was either adequate Se (ASe, 9.5 MUg/kg of BW) or high
      Se (HSe, 81.8 MUg/kg of BW) in Exp. 1 or ASe (11.5 ug/kg of BW) or HSe (77.0
      ug/kg of BW) in Exp. 2. On d 50 or 40 of gestation for Exp. 1 or 2, respectively,
      ewes were assigned randomly to 1 of 3 nutritional planes: 60% (RES), 100%
      (control, CON), or 140% (HI) of NRC requirements. This resulted in the following
      treatments: ASe-RES, ASe-CON, ASe-HI, HSe-RES, HSe-CON, and HSe-HI. Upon
      parturition, lambs were separated from their dams and serum samples obtained.
      Lambs were fed artificial colostrum for the first 20 h and then placed on milk
      replacer and grain pellets until completion of the study (Exp. 1, 57 d; Exp. 2,
      21 d). Twenty-four hours after parturition, lamb serum samples were collected for
      IgG analysis. All lambs were reared similarly and morbidity and mortality
      assessed. Main effects were considered significant when P <= 0.05. In Exp. 1,
      there was a Se * plane of nutrition interaction (P <= 0.01) for lamb morbidity
      from birth to weaning and for 24-h IgG concentration. Lambs from ASe-RES and HSe
      HI ewes were treated more frequently (P < 0.01) for respiratory and
      gastrointestinal disease, and lambs from HSe-HI ewes had the smallest (P < 0.01)
      24-h serum IgG concentration. In Exp. 1, lambs from HI ewes also had the greatest
      (P < 0.01) mortality rates from birth to weaning compared with lambs from CON and
      RES ewes. In Exp. 2, there was an effect (P < 0.01) of maternal plane of
      nutrition with lambs from RES ewes having increased 24-h IgG compared with lambs
      from CON and HI ewes. There was no effect of maternal Se supplementation on lamb
      24-h IgG in Exp. 2; however, there was a Se * plane of nutrition interaction (P <
      0.01) for morbidity. From birth to 21 d of age, lambs from ASe-CON ewes had fewer
      (P < 0.01) treatment days compared with lambs from any of the other treatment
      groups. There also tended (P = 0.08) to be an effect of maternal Se
      supplementation on lamb mortality with increased mortality observed in lambs from
      HSe ewes. Results from the studies show a restricted maternal plane of nutrition
      can increase lamb serum IgG concentration. Selenium results were not consistent
      between the 2 experiments and may be due to differences in maternal Se.

PMID- 21724939
TI  - Effects of sex and age on genotype x environment interaction for beef cattle body
      weight studied using reaction norm models.
AB  - The interest in the effect of genotype * environment interaction is increasing
      because animal breeding programs have become geographically broader. Climate
      changes in the next decades are also expected to challenge the present breeding
      goals, increasing the importance of environmental sensitivity. The aim of this
      work was to analyze genotype * environment interaction effect on cattle BW using
      the environmental sensitivity predicted by random regression reaction norm
      models, including sex and age effects as additional dimensions in the study.
      Genetic parameters were estimated for adjusted BW of Brazilian Nelore cattle at
      different ages (120, 210, 365, and 450 d), using linear polynomials for random
      regression analysis. The analyses with sex as a fixed effect (total analyses)
      were compared with those with sex-separated progenies (male and female progeny
      analyses, respectively). (Co)variance components were estimated and breeding
      values calculated EPD. The results showed important differences in reaction norm
      model genetic parameter estimates according to different age and sex analyses.
      The results confirmed the presence of an important genotype * environment * sex *
      age interaction for Nelore cattle BW. The patterns in these results lead to a
      revision of the importance of sexual and developmental factors on plasticity and
      adaptation concepts.

PMID- 21724940
TI  - Effects of restricted feed intake on heat energy by different goat breeds.
AB  - Sixteen Boer goat doelings, 16 Spanish doelings, and 8 Angora doelings and 8
      wethers, 283, 316, and 330 d of age initially (SEM = 5.0), respectively, were
      used to evaluate effects of nutrient restriction on heat energy (HE). During the
      first and second 10-wk phases, 8 animals of each breed were fed a 50% concentrate
      pelletized diet at a level adequate for maintenance and moderate energy accretion
      (CONT). Other animals were fed approximately 50% of these amounts in phase 1
      relative to initial BW, followed by the greater level of feeding in phase 2 based
      on initial or actual BW when greater (REST). Average daily gain was 43, -20, 16, 
      78, 8, and -48 g in phase 1 (SEM = 5.0) and 26, 44, 50, 65, 27, and 32 g in phase
      2 (SEM = 3.5) for Angora-CONT, Angora-REST, Boer-CONT, Boer-REST, Spanish-CONT,
      and Spanish-REST, respectively. Total HE was greater for CONT vs. REST in both
      phases (P < 0.001), greater in phase 1 for Angora than for Boer (P < 0.01) and
      Spanish (P < 0.01), and greatest (P < 0.01) in phase 2 among breeds for Angora
      [481, 347, 430, 356, 424, and 338 kJ/kg of BW(0.75) per day in phase 1 (SEM =
      11.1), and 494, 479, 445, 397, 444, and 406 kJ/kg of BW(0.75) per day in phase 2
      (SEM = 11.3) for Angora-CONT, Angora-REST, Boer-CONT, Boer-REST, Spanish-CONT,
      and Spanish-REST, respectively]. Equations describing the temporal pattern of HE
      (kJ/kg of BW(0.75) per day), expressed as a percentage of the wk-0 value and
      corrected for corresponding breed * week CONT means, in phase 1 were 95.8 +/-
      2.43 - (8.18 +/- 1.144 * week) + (0.655 +/- 0.1098 * week(2)) for Angora (R(2) =
      0.58), 95.3 +/- 2.63 - (4.34 +/- 1.237 * wk) + (0.271 +/- 0.1187 * wk(2)) for
      Boer (R(2) = 0.41), and 97.4 +/- 2.21 - (4.69 +/- 1.068 * wk) + (0.282 +/- 0.1021
      * wk(2)) for Spanish (R(2) = 0.53). Phase 2 equations were 78.9 +/- 2.22 + (8.74
      +/- 1.036 * wk) - (0.608 +/- 0.0095 * wk(2)) for Angora (R(2) = 0.60), 77.5 +/-
      2.10 + (3.30 +/- 0.978 * wk) - (0.153 +/- 0.0942 * wk(2)) for Boer (R(2) = 0.39),
      and 80.6 +/- 2.50 + (4.50 +/- 1.165 * wk) - (0.208 +/- 0.1122 * wk(2)) for
      Spanish (R(2) = 0.43). These equations indicate that changes in HE in response to
      nutrient restriction and realimentation were more rapid and of greater magnitude
      in Angora vs. Boer and Spanish. The temporal pattern of decline in HE by Boer and
      Spanish during restriction was similar, but the subsequent rise with
      realimentation was slower and smaller for Boer. In conclusion, most appropriate
      methods of predicting change in the maintenance energy requirement during and
      after periods of limited feed intake may differ among breeds of goats.

PMID- 21724941
TI  - Circulating ghrelin and leptin concentrations and growth hormone secretagogue
      receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting
      differences in composition of gain.
AB  - Data from species other than cattle indicate that ghrelin and GH secretagogue
      receptor (GHS-R) could play a key role in fat deposition, energy homeostasis, or
      glucose metabolism by directly affecting liver and adipose tissue metabolism.
      Beef steers (n = 72) were used to test the hypothesis that plasma ghrelin and
      leptin concentrations and abundance of the GHS-R in liver, muscle, and adipose
      tissues differ in steers exhibiting differences in composition of gain. At trial
      initiation (d 0), 8 steers were slaughtered for initial carcass composition. The
      remaining 64 steers were stratified by BW, allotted to pen, and treatment was
      assigned randomly to pen. Steers were not implanted with anabolic steroids.
      Treatments were 1) a low-energy (LE) diet fed during the growing period (0 to 111
      d) followed by a high-energy (HE) diet during the finishing period (112 to 209 d;
      LE-HE) or 2) the HE diet for the duration of the trial (1 to 209 d; HE-HE). Eight
      steers per treatment were slaughtered on d 88, 111, 160, and 209. Carcass ninth,
      tenth, and eleventh rib sections were dissected for chemical composition and
      regression equations were developed to predict compositional gain. Liver, muscle,
      and subcutaneous adipose tissues were frozen in liquid nitrogen for subsequent
      Western blotting for GHS-R. Replicate blood samples collected before each
      slaughter were assayed for ghrelin and leptin concentrations. When compared at a
      common compositional fat end-point, the rate of carcass fat accretion (g.kg of
      shrunk BW(-1)) was greater (P < 0.001) in HE-HE steers whereas the rate of
      carcass protein accretion (g.kg of shrunk BW(-1)) was less (P < 0.001) compared
      with LE-HE steers. When compared at a common compositional fat end-point, plasma
      leptin, ghrelin, and insulin concentrations were greater (P < 0.05) for HE-HE
      compared with LE-HE steers. Abundance of the GHS-R, to which ghrelin binds,
      increased over time in liver and adipose tissue but did not differ as a result of
      treatment. Plasma ghrelin concentrations were increased for cattle continuously
      fed the HE diet as they became increasingly fatter; however, abundance of the GHS
      R in liver, muscle, and subcutaneous adipose tissue was not different between
      treatment groups. The role of ghrelin in cattle metabolism warrants further
      investigation as it could have a significant effect on composition of BW gain,
      feed efficiency, and metabolic disorders such as ketosis and fatty liver.

PMID- 21724942
TI  - Study of the effect of presence or absence of protozoa on rumen fermentation and
      microbial protein contribution to the chyme.
AB  - The aim of this study was to investigate the effect of presence or absence of
      protozoa on rumen fermentation and efficiency of microbial protein synthesis
      under different diets. Of 20 twin paired lambs, 1 lamb of each pair was isolated
      from the ewe within 24 h after birth and reared in a protozoa-free environment (n
      = 10), whereas their respective twin-siblings remained with the ewe (faunated, n
      = 10). When lambs reached 6 mo of age, 5 animals of each group were randomly
      allocated to 1 of 2 experimental diets consisting of either alfalfa hay as the
      sole diet, or 50:50 mixed with ground barley grain according to a 2 * 2 factorial
      arrangement of treatments. After 15 d of adaptation to the diet, the animals were
      euthanized and total rumen and abomasal contents were sampled to estimate rumen
      microbial synthesis using C(31) alkane as flow marker. Different ((15)N and
      purine bases) and a novel (recombinant DNA sequences) microbial markers, combined
      with several microbial reference extracts (rumen protozoa, liquid and solid
      associated bacteria) were evaluated. Absence of rumen protozoa modified the rumen
      fermentation pattern and decreased total tract OM and NDF digestibility in 2.0
      and 5.1 percentage points, respectively. The effect of defaunation on microbial N
      flow was weak, however, and was dependent on the microbial marker and microbial
      reference extract considered. Faunated lambs fed with mixed diet showed the
      greatest rumen protozoal concentration and the least efficient microbial protein
      synthesis (29% less than the other treatments), whereas protozoa-free lambs fed
      with mixed diet presented the smallest ammonia concentration and 34% greater
      efficiency of N utilization than the other treatments. Although (15)N gave the
      most precise estimates of microbial synthesis, the use of recombinant DNA
      sequences represents an alternative that allows separate quantification of the
      bacteria and protozoa contributions. This marker showed that presence of protozoa
      decrease the bacterial-N flow through the abomasum by 33%, whereas the protozoa-N
      contribution to the microbial N flow increased from 1.9 to 14.1% when barley
      grain was added to the alfalfa hay. Absolute data related to intestinal flow must
      be treated with caution because the limitations of the sampling and maker system
      employed.

PMID- 21724943
TI  - Feed supplemented with 3 different antibiotics improved food intake and decreased
      the activation of the humoral immune response in healthy weaned pigs but had
      differing effects on intestinal microbiota.
AB  - The aim of this study was to determine the effects of 3 antibiotics used for
      pulmonary pathologies added in the feed of weaned pigs on growth performance,
      commensal microbiota, and immune response. At weaning, a total of 72 pigs were
      randomly assigned by BW and litter to 1 of the following diets: control (typical
      weaning diet), control + 400 mg of tilmicosin/kg, control + 600 mg of
      amoxicillin/kg, and control + 300 mg of doxycycline/kg. Individually penned pigs
      were slaughtered after 3 wk (12 pigs/treatment) or 4 wk (6 pigs/treatment).
      During the fourth week, all pigs received the control diet to test the residual
      effect of the antimicrobial supplementation. The antibiotic supplementation
      increased growth and feed intake during the first week (P < 0.01) and over the
      first 3 wk combined (P < 0.05). Gain-to-feed ratio tended to improve during the
      first week (P = 0.076) by the antibiotics compared with the control. Among the
      antibiotic treatments, no difference was observed in ADG and feed intake, which
      were also unchanged by the diet in the fourth week. The fecal enterobacteria
      counts were increased by amoxicillin on d 14 and 21 (P < 0.05 and 0.01,
      respectively) and were decreased by tilmicosin (P < 0.001) compared with the
      control. Amoxicillin decreased lactic acid bacteria (P < 0.01) counts compared
      with the control. The antibiotic supplementation tended to decrease total
      bacteria variability in the jejunum (Shannon index, P = 0.091) compared with the
      control. The antibiotic treatment decreased the mean total serum IgM
      concentration (P = 0.016) after 3 wk and did not change the mucosal
      histomorphometry of the small intestine. For tilmicosin, the observed positive
      action on piglet performance and feed intake can originate by the decreased costs
      of immune activation determined by the action on intestinal microbiota. For
      amoxicillin and doxycycline, the observation on intestinal and fecal microbiota
      seems to be not sufficient to explain their growth-promoting effect.

PMID- 21724944
TI  - Technical note: Development of an enzyme-linked immunosorbent assay for the
      determination of florfenicol and thiamphenicol in swine feed.
AB  - One polyclonal antibody against florfenicol and thiamphenicol was produced and a
      competitive ELISA was developed for the detection of florfenicol and
      thiamphenicol in swine feed. The ELISA gave a 50% inhibiting concentration of
      1.02 ng/mL for florfenicol. For swine feed fortified with 0.05 to 3.0 mg/kg, the
      interassay recoveries of florfenicol and thiamphenicol ranged from 86.4 to
      118.6%, whereas intraassay recoveries of both drug ranged from 90.1 to 126.5%
      with less than 15% CV. Results obtained from HPLC-tandem mass spectrometry
      indicated this ELISA procedure could be used as a convenient method for rapid
      screening of florfenicol and thiamphenicol in swine feed.

PMID- 21724945
TI  - Apparent and standardized ileal digestibilities of amino acids for pigs fed corn-
      and soybean meal-based diets at varying crude protein levels.
AB  - The objective of this study was to determine the effect of CP level in corn- and
      soybean meal-based diets on apparent (AID) and standardized ileal digestibility
      (SID) of AA. Six pigs (initial BW, 47.1 +/- 1.0 kg) fitted with T-cannula at the
      distal ileum were fed 6 diets for 6 periods in a 6 * 6 Latin square design. The 6
      diets consisted of a nitrogen-free diet and 5 corn- and soybean meal-based diets
      that contained CP of 68, 105, 141, 177, and 214 g/kg. Each period consisted of a
      5-d adjustment period and 2 d of ileal digesta collection for 10 h on each of d 6
      and 7. The ratio of corn:soybean meal was fixed at 3 to 2 by weight and
      cornstarch was added to dilute the CP concentration. Chromic oxide was added at 5
      g/kg as an indigestible marker. The results showed basal endogenous loss ranged
      from 65 mg/kg of DMI for Met to 3,104 mg/kg of DMI for Pro. Proline and Gly
      (1,053 mg/kg of DMI) were the 2 most abundant AA in endogenous flow and together
      accounted for approximately 43% of the total endogenous AA flow. Of the basal
      ileal endogenous CP, total AA accounted for 82%. The AID were 80.9 to 84.7%, 85.1
      to 87.4%, 72.9 to 79.5%, and 86.5 to 87.9% for Lys, Met, Thr, and Trp,
      respectively, with corresponding SID being 86.6 to 89.0%, 87.5 to 90.5%, 82.7 to
      88.2%, and 90.2 to 94.6%, respectively, as dietary CP increased from 68 to 214
      g/kg. There were linear increases in AID of N, Arg, Gly, Ile, Lys, Ser, Thr, Tyr,
      and Val (P <= 0.05) as CP increased and linear decreases in SID of N and all AA
      measured in this study except Lys, Met, and Pro (P <= 0.05). Both linear and
      quadratic effects were observed in AID for Pro (P < 0.05). In conclusion, the
      protein content of corn-soybean meal diets evaluated in the current study
      affected SID of most indispensable and dispensable AA, excluding Lys, Met, and
      Pro.

PMID- 21724946
TI  - Effect of sire breed and genetic merit for carcass weight on the transcriptional
      regulation of the somatotropic axis in longissimus dorsi of crossbred steers.
AB  - The somatotropic axis plays an important role in postnatal growth, development,
      and differentiation of skeletal muscle. The aim of this study was to examine the
      effect of sire breed and sire EPD for carcass weight (EPD(cwt)) on the expression
      of components of the somatotropic axis in LM of beef cattle at slaughter.
      Crossbred Aberdeen Angus (AA; n = 17) and Belgian Blue (BB; n = 16) steers born
      to Holstein-Friesian dams and sired by bulls with either high (H) or low (L)
      EPD(cwt) were used in the study. Thus, there were 4 genetic groups [i.e., BBH (n
      = 8), BBL (n = 8), AAH (n = 8), and AAL (n = 9)]. Blood samples were collected
      via jugular venipuncture at regular intervals for analysis of plasma
      concentrations of IGF-1 and insulin. Total RNA was isolated from LM collected at
      slaughter, and the mRNA expression of IGF-1, IGF-2, their receptors (IGF-1R; IGF
      2R), 6 IGFBP, acid labile subunit (ALS), and GH receptor (GHR) was measured by
      real-time reverse-transcription quantitative PCR. There was no effect of either
      sire breed or EPD(cwt) on concentrations of circulating IGF or insulin (P >
      0.05). Gene expression of IGF-1R and IGFBP3 was upregulated in AA (P < 0.001)
      compared with BB, whereas IGF-1 was upregulated in H compared with L animals (P <
      0.01). Correlation analysis indicated moderate positive associations between gene
      expression of IGFBP3 and IGF-1 (r = 0.54; P < 0.001) and IGF-1R (r = 0.48; P <
      0.01). In addition, correlation analysis revealed that mRNA expression of IGFBP3
      was moderately negatively associated with LM area per kilogram of carcass weight
      (r = -0.40; P < 0.05). Greater gene expression of IGF-1 and reduced transcript
      abundance of IGFBP3 in muscle may have a role in increased muscle growth
      potential in steers during the finishing period. These data will contribute to a
      better understanding of the molecular control of muscle growth at a tissue level
      in cattle.

PMID- 21724947
TI  - The influence of tropical adaptation on plasma concentrations of insulin-like
      growth factor-I in purebred and crossbred beef cattle.
AB  - In an effort to determine whether tropical adaptation influences circulating
      concentrations of the growth-related hormone IGF-I, 3-breed diallel matings were
      conducted using temperate Bos taurus (Angus), tropical Bos indicus (Brahman), and
      tropical Bos taurus (Romosinuano). Purebred Angus, Braham, and Romosinuano and
      crossbred Angus-Braham, Angus-Romosinuano, and Braham-Romosinuano heifers and
      steers were evaluated in 2 separate calf crops from 2003 and 2004. Blood samples
      were obtained from 10 heifers of each breed group (n = 90) for each year at
      weaning and on d 0 and 84 of postweaning trials. Samples were also taken from 10
      steers of each breed group (n = 90) at weaning and on d 0 and 60 of individual
      finishing phase feeding trials for each year. Concentrations of IGF-I were
      determined by RIA. Analyses included effects of sire breed, dam breed, year of
      record, the age of the dam of the calf in years, and interactions. Age of calf in
      days was investigated as a linear and quadratic covariate. Separate analyses were
      conducted for steers and heifers. The direct effect of Angus was to reduce (P <
      0.03) heifer concentrations of IGF-I at d 84 and in the repeated measures
      analysis. In the repeated measures analysis, the direct effect of Romosinuano was
      to increase concentrations of IGF-I (P = 0.01). Relative to the temperate Bos
      taurus breed, plasma concentrations of IGF-I were numerically greater in male and
      female tropically adapted breed groups.

PMID- 21724948
TI  - Identifying fingerprint expertise.

PMID- 21724949
TI  - Knowing your own mate value: sex-specific personality effects on the accuracy of
      expected mate choices.
AB  - Knowing one's mate value (mate-value accuracy) is an important element in
      reproductive success. We investigated within- and between-sex differences in this
      ability in a real-life speed-dating event. A total of 190 men and 192 women
      filled out a personality questionnaire and participated in speed-dating sessions.
      Immediately after each date, participants recorded who they would choose as mates
      and who they expected would choose them. In line with evolutionarily informed
      hypotheses, results indicated that sociosexually unrestricted men and more
      agreeable women showed greater mate-value accuracy than sociosexually restricted
      men and less agreeable women, respectively. These results have important
      implications for understanding mating behavior and perhaps the origin of sex
      differences in personality.

PMID- 21724950
TI  - Semagacestat pharmacokinetics are not significantly affected by formulation,
      food, or time of dosing in healthy participants.
AB  - Semagacestat, a gamma-secretase inhibitor, reduces formation of amyloid beta
      peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover
      studies evaluated the effect of formulation, food, and time of dosing on the
      pharmacokinetics and pharmacodynamics of semagacestat in healthy participants.
      The first study (n = 14) compared tablet to capsules. For all formulations, the
      median time to maximum plasma concentration (t(max)) was generally 1.0 hour.
      Plasma elimination was rapid, with a half-life of approximately 2.5 hours. Tablet
      form II bioavailability (F) relative to capsule was approximately 100% (F = 1.03
      [90% confidence interval (CI), 0.96-1.10]). In the second study, participants (n
      = 27) received semagacestat either fed or fasting in the morning or fasting in
      the evening. No significant change in exposure (AUC(0-infinity) [area under the
      concentration-time curve from 0 to infinity] ratio = 1.02, [90% CI, 0.990-1.05])
      occurred with food, whereas maximum plasma concentration (C(max)) declined
      approximately 15%, and median t(max) was delayed to 1.5 hours. Time of dosing
      made no significant difference in AUC(0-infinity), C(max), or t(max) (AUC(0
      infinity) ratio 1.01, [90% CI, 0.975-1.04]). No clinically significant safety
      concerns occurred in either study. Accordingly, semagacestat may be dosed without
      regard to formulation, food, or time of administration.

PMID- 21724951
TI  - Streptomyces pharmamarensis sp. nov. isolated from a marine sediment.
AB  - A Gram-stain-positive actinobacterium, strain PM267(T), was isolated from a
      marine sediment sample in the Mediterranean Sea. The novel strain produced
      extensively branched substrate and aerial hyphae that carried spiral spore
      chains. Substrate and aerial mycelia were cream-white and white, respectively.
      Diffusible pigments were not observed. 16S rRNA gene sequence analysis revealed
      that strain PM267(T) belonged to the genus Streptomyces and shared a gene
      sequence similarity of 97.1 % with Streptomyces artemisiae YIM 63135(T) and
      Streptomyces armeniacus JCM 3070(T). Values <97 % were obtained with other
      sequences representing members of the genus Streptomyces. The cell wall
      peptidoglycan contained ll-diaminopimelic acid. MK-9(H(8)) was the major
      menaquinone. The phospholipid pattern included phosphatidylethanolamine as
      diagnostic lipid (type II). Major fatty acids found were iso- and anteiso- fatty
      acids. The G+C content of the DNA was 71.2 mol%. The strain was halotolerant and
      was able to grow in the presence of 9 % (w/v) NaCl (with an optimum of 2 %). On
      the basis of these results and additional physiological data obtained in the
      present study, strain PM267(T) represents a novel species within the genus
      Streptomyces for which the name Streptomyces pharmamarensis sp. nov. is proposed
      (type strain PM267(T)  = CECT 7841(T)  = DSM 42032(T)).

PMID- 21724952
TI  - Moorea producens gen. nov., sp. nov. and Moorea bouillonii comb. nov., tropical
      marine cyanobacteria rich in bioactive secondary metabolites.
AB  - The filamentous cyanobacterial genus Moorea gen. nov., described here under the
      provisions of the International Code of Botanical Nomenclature, is a cosmopolitan
      pan-tropical group abundant in the marine benthos. Members of the genus Moorea
      are photosynthetic (containing phycocyanin, phycoerythrin, allophycocyanin and
      chlorophyll a), but non-diazotrophic (lack heterocysts and nitrogenase reductase
      genes). The cells (discoid and 25-80 um wide) are arranged in long filaments (<10
      cm in length) and often form extensive mats or blooms in shallow water. The cells
      are surrounded by thick polysaccharide sheaths covered by a rich diversity of
      heterotrophic micro-organisms. A distinctive character of this genus is its
      extraordinarily rich production of bioactive secondary metabolites. This is
      matched by genomes rich in polyketide synthase and non-ribosomal peptide
      synthetase biosynthetic genes which are dedicated to secondary metabolism. The
      encoded natural products are sometimes responsible for harmful algae blooms and,
      due to morphological resemblance to the genus Lyngbya, this group has often been
      incorrectly cited in the literature. We here describe two species of the genus
      Moorea: Moorea producens sp. nov. (type species of the genus) with 3L(T) as the
      nomenclature type, and Moorea bouillonii comb. nov. with PNG5-198(R) as the
      nomenclature type.

PMID- 21724953
TI  - Flavobacterium xueshanense sp. nov. and Flavobacterium urumqiense sp. nov., two
      psychrophilic bacteria isolated from glacier ice.
AB  - Two Gram-stain-negative, rod-shaped bacteria, designated strains Sr22(T) and
      Sr25(T), were isolated from water of melted ice from the China No.1 glacier,
      Xinjiang Uygur Autonomous Region, China. Cells formed yellow, circular, convex
      colonies. 16S rRNA gene sequence analysis indicated that strains Sr22(T) and
      Sr25(T) belong to the genus Flavobacterium, sharing <=99.1  and <=99.6 %
      similarity, respectively, with the type strains of recognized species of the
      genus. Strain Sr22(T) shared highest 16S rRNA gene sequence similarity with
      Flavobacterium tiangeerense CGMCC 1.6847(T) (98.6 %), Flavobacterium fryxellicola
      LMG 22022(T) (98.1 %) and Flavobacterium omnivorum CGMCC 1.2747(T) (99.1 %).
      Strain Sr25(T) shared highest similarity with Flavobacterium sinopsychrotolerans
      CGMCC 1.8704(T) (98.5 %), Flavobacterium degerlachei NBRC 102677(T) (98.4 %) and
      Flavobacterium xinjiangense CGMCC 1.2749(T) (99.5 %). The predominant fatty acids
      of strain Sr22(T) were iso-C(15 : 1) G (6.01 %), iso-C(15 : 0) (8.93 %), iso-C(16
      : 1) H (12.68 %), iso-C(16 : 0) (10.4 %), C(15 : 1)omega6c (8.97 %), C(17 :
      1)omega6c (5.96 %), iso-C(16 : 0) 3-OH (11.14 %) and summed feature 3 (comprising
      C(16 : 1)omega7c and/or C(16 : 1)omega6c, 12.33 %). The major fatty acids of
      strain Sr25(T) were iso-C(15 : 0) (10.8 %), anteiso-C(15 : 0) (5.23 %), C(15 :
      1)omega6c (11.79 %), C(17 : 1)omega6c (5.43 %), iso-C(16 : 0) 3-OH (7.04 %) and
      summed feature 3 (20.42 %). The genomic DNA G+C contents of strains Sr22(T) and
      Sr25(T) were 37.2 and 35.1 mol%. On the basis of differential phenotypic and
      phylogenetic characteristics, these strains are considered to represent two novel
      species of the genus Flavobacterium, for which the names Flavobacterium
      xueshanense sp. nov. (type strain Sr22(T)  = CGMCC 1.9227(T)  = NBRC 106479(T))
      and Flavobacterium urumqiense sp. nov. (type strain Sr25(T)  = CGMCC 1.9230(T)  =
      NBRC 106480(T)) are proposed.

PMID- 21724954
TI  - Spongiibacterium flavum gen. nov., sp. nov., a member of the family
      Flavobacteriaceae isolated from the marine sponge Halichondria oshoro, and
      emended descriptions of the genera Croceitalea and Flagellimonas.
AB  - A gram-negative, strictly aerobic, non-flagellated, non-gliding, oxidase- and
      catalase-positive, yellow-pigmented rod, designated A11(T), was isolated from a
      marine sponge, Halichondria oshoro, collected on the coastline of Jeju Island,
      Republic of Korea. Phylogenetic analysis based on nearly complete 16S rRNA gene
      sequences revealed that strain A11(T) was a member of the family
      Flavobacteriaceae. Its closest relatives were members of the genera Muricauda,
      Flagellimonas and Croceitalea (94.4-94.8 % 16S rRNA gene sequence similarity).
      The only polar lipid detected in strain A11(T) was phosphatidylethanolamine. The
      dominant fatty acids were iso-C(15 : 0) (30.4 %), iso-C(15 : 1) G (26.7 %), iso
      C(17 : 0) 3-OH (12.4 %) and iso-C(15 : 0) 3-OH (7.3 %). The DNA G+C content of
      strain A11(T) was 41.7 mol% and its major respiratory quinone was MK-6. On the
      basis of combined data from phenotypic and phylogenetic analyses, strain A11(T)
      represents a novel genus and species within the family Flavobacteriaceae, for
      which the name Spongiibacterium flavum gen. nov., sp. nov. is proposed. The type
      strain of the type species is A11(T) ( = KCTC 22665(T) = DSM 22638(T)). Emended
      descriptions of the genera Croceitalea and Flagellimonas are also given.

PMID- 21724955
TI  - Bacteroides stercorirosoris sp. nov. and Bacteroides faecichinchillae sp. nov.,
      isolated from chinchilla (Chinchilla lanigera) faeces.
AB  - Strains of gram-negative anaerobic rods were isolated from chinchilla (Chinchilla
      lanigera) faeces, and three strains, ST161(T), ST33 and ST37(T), were
      investigated taxonomically. Based on phylogenetic analyses and specific
      phenotypic characteristics, the three strains were allocated to the genus
      Bacteroides. Phylogenetic analyses of their 16S rRNA gene sequences revealed that
      strain ST161(T) formed a distinct line of descent, with highest sequence
      similarity to strain ST33 (98.7 %) and Bacteroides oleiciplenus JCM 16102(T)
      (97.7 %). High levels of DNA-DNA relatedness (79-89 %) were found between strains
      ST161(T) and ST33, but low levels were found between strain ST161(T) and B.
      oleiciplenus JCM 16102(T) (33-37 %) and between strain ST33 and B. oleiciplenus
      JCM 16102(T) (33-37 %). These data clearly indicated that strains ST161(T) and
      ST33 represent a single novel species. 16S rRNA gene sequence analyses showed
      that strain ST37(T) also formed a distinct line of descent, with highest sequence
      similarity to Bacteroides acidifaciens JCM 10556(T) (96.5 %) and Bacteroides
      caccae JCM 9498(T) (95.6 %). Analysis of hsp60 gene sequences also supported
      these relationships. Based on phenotypic and phylogenetic characteristics, two
      novel species, Bacteroides stercorirosoris sp. nov. and Bacteroides
      faecichinchillae sp. nov., are thus proposed. The type strains of B.
      stercorirosoris and B. faecichinchillae are ST161(T) ( = JCM 17103(T) = CCUG
      60872(T)) and ST37(T) ( = JCM 17102(T) = CCUG 60873(T)), respectively. The DNA
      G+C contents of strains ST161(T) and ST37(T) were 45.7 and 41.0 mol%,
      respectively.

PMID- 21724956
TI  - Muricauda beolgyonensis sp. nov., isolated from a tidal flat.
AB  - The taxonomic position of a Gram-staining-negative, non-motile, rod-shaped
      bacterium, strain BB-My12(T), which was isolated from a sediment sample collected
      from a tidal flat in Korea, was investigated by using a polyphasic approach.
      Strain BB-My12(T) grew optimally at 37  degrees C, at pH 7.0-7.5 and in the
      presence of 2-3 % (w/v) NaCl. In phylogenetic analyses based on 16S rRNA gene
      sequences, strain BB-My12(T) fell within the cluster comprising species of the
      genus Muricauda and appeared most similar to the type strains of Muricauda
      aquimarina, Muricauda lutimaris and Muricauda ruestringensis (97.5-97.6 %
      sequence similarity). The DNA G+C content was 45.0 mol%. Strain BB-My12(T)
      contained MK-6 as the predominant menaquinone and iso-C(15 : 1), iso-C(17 : 0) 3
      OH and iso-C(15 : 0) as the major cellular fatty acids. The polar lipids of
      strain BB-My12(T) were phosphatidylethanolamine and four unidentified lipids. The
      DNA-DNA relatedness values between strain BB-My12(T) and the type strains of the
      three species of the genus Muricauda that appeared most closely related were in
      the range 5-7 %. The genetic distinctiveness and some phenotypic properties
      indicated that strain BB-My12(T) did not belong to any established species of the
      genus Muricauda. Strain BB-My12(T) is therefore considered to represent a novel
      species of the genus Muricauda, for which the name Muricauda beolgyonensis sp.
      nov. is proposed. The type strain is BB-My12(T) ( = KCTC 23501(T)  = CCUG
      60800(T)).

PMID- 21724957
TI  - Lactobacillus nasuensis sp. nov., a lactic acid bacterium isolated from silage,
      and emended description of the genus Lactobacillus.
AB  - Two strains of lactic acid bacteria, designated SU 18(T) and SU 83, were isolated
      from silage prepared with Sudan grass [Sorghum sudanense (Piper) Stapf.]. The
      isolates were Gram-stain-positive, catalase-negative, facultatively anaerobic
      rods that did not produce gas from glucose. The isolates exhibited >=93.5 % DNA
      DNA relatedness to each other and shared the same phenotypic characteristics,
      which indicated that they belonged to a single species. The DNA G+C content was
      58.5-59.2 mol%. On the basis of 16S rRNA gene sequence analysis, the isolates
      were placed in the genus Lactobacillus. Their closest phylogenetic neighbours
      were Lactobacillus manihotivorans JCM 12514(T) and Lactobacillus camelliae JCM
      13995(T) (95.9 and 96.8 % 16S rRNA gene sequence similarity, respectively, with
      strain SU 18(T)). Ribotyping revealed that strain SU 18(T) was well separated
      from L. manihotivorans JCM 12514(T) and L. camelliae JCM 13995(T). Strain SU
      18(T) exhibited <=23.7 % DNA-DNA relatedness with its closest phylogenetic
      neighbours. The isolates represent a novel species in the genus Lactobacillus,
      for which the name Lactobacillus nasuensis sp. nov. is proposed. The type strain
      is SU 18(T) ( = JCM 17158(T)  = CGMCC 1.10801(T)). The description of the genus
      Lactobacillus is also amended.

PMID- 21724958
TI  - Shewanella arctica sp. nov., an iron-reducing bacterium isolated from Arctic
      marine sediment.
AB  - Two strains of dissimilatory iron-reducing bacteria, which could couple lactate
      oxidation to iron reduction for energy conservation, were isolated from Arctic
      marine sediment. The strains, IR12(T) and IR26, were both Gram-staining-negative,
      catalase- and oxidase-positive and facultative anaerobes. Their cells were rod
      shaped and motile by means of a polar flagellum. Both strains grew in the
      presence of 0.5-3.5 % (w/v) NaCl, with an absolute requirement for Na(+). Both
      were psychrotolerant since they could grow at 4-28  degrees C but had an optimum
      growth temperature of 20  degrees C. Both grew at pH 4.5-9.0 (optimum, pH 7.5).
      The major fatty acids of strains IR12(T) and IR26 were summed feature 3 (C(16 :
      1)omega6c and/or C(16 : 1)omega7c) and C(16 : 0). Phylogenetic analyses based on
      16S rRNA gene sequences indicated that strains IR12(T) and IR26 belonged to the
      class Gammaproteobacteria and were most closely related to Shewanella vesiculosa
      M7(T), Shewanella livingstonensis NF22(T) and Shewanella frigidimarina ACAM
      591(T) (with 98.5 and 98.8 %, 98.5 and 98.8 %, and 98.5 and 98.8 % sequence
      similarities, respectively). The genomic DNA G+C contents of strains IR12(T) and
      IR26 were 40.0 and 40.3 mol%, respectively. DNA-DNA relatedness data indicated
      that the two novel strains represented a single species that was distinct from S.
      vesiculosa M7(T), S. livingstonensis NF22(T) and S. frigidimarina ACAM 591(T).
      Based on the phylogenetic, phenotypic and DNA-DNA relatedness data, the two new
      strains represent a single novel species of the genus Shewanella, for which the
      name Shewanella arctica sp. nov. is proposed. The type strain is IR12(T) ( = KCTC
      23109(T) = JCM 16723(T)).

PMID- 21724959
TI  - Lysinibacillus macroides sp. nov., nom. rev.
AB  - 'Bacillus macroides' ATCC 12905(T) ( = DSM 54(T) = LMG 18474(T)), isolated in
      1947 from cow dung, was not included in the Approved Lists of Bacterial Names and
      so it lost standing in bacteriological nomenclature. Reinvestigation of the
      strain, including DNA-DNA relatedness experiments, revealed that 'Bacillus
      macroides' is genomically distinct from its closest relatives Lysinibacillus
      xylanilyticus, Lysinibacillus boronitolerans and Lysinibacillus fusiformis (as
      determined by 16S rRNA gene sequence analysis, with pairwise similarity values of
      99.2, 98.8 and 98.5 %, respectively, with the type strains of these species).
      Further analysis showed that 'Bacillus macroides' shares the A4alpha L-Lys-D-Asp
      peptidoglycan type with other members of the genus Lysinibacillus and can thus be
      attributed to this genus. These results, combined with additional phenotypic
      data, justify the description of strain LMG 18474(T) ( = DSM 54(T) = ATCC
      12905(T)) as Lysinibacillus macroides sp. nov., nom. rev.

PMID- 21724960
TI  - Camelimonas abortus sp. nov., isolated from placental tissue of cattle.
AB  - A gram-negative, rod-shaped, non-spore-forming bacterium, isolated from placental
      tissue of a cow, was investigated for its taxonomic position. On the basis of 16S
      rRNA gene sequence similarities, strain UK34/07-5(T) was shown to belong to the
      class Alphaproteobacteria, closely related to the type strain of Camelimonas
      lactis (96.0 % sequence similarity). The polyamine pattern showed the major
      compound spermidine and moderate amounts of putrescine. The major quinone was
      ubiquinone Q-10. The polar lipid profile was composed of the major compounds
      phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol and
      phosphatidylmonomethylethanolamine and moderate amounts of
      diphosphatidylglycerol, three unidentified aminolipids and an unidentified
      phospholipid. The profile of major fatty acids, consisting of C(19 : 0) cyclo
      omega8c and C(18 : 1)omega7c, with C(18 : 0) 3-OH as the hydroxylated fatty acid,
      was very similar to that of C. lactis M 2040(T). The results of DNA-DNA
      hybridization and physiological and biochemical tests allowed both genotypic and
      phenotypic differentiation of the isolate from C. lactis. The relatively low 16S
      rRNA gene sequence similarity of 96.0 % to C. lactis M 2040(T) and marked
      differences in the polar lipid profiles as well as the results of physiological
      tests and the DNA-DNA hybridization data support the creation of a novel species,
      for which the name Camelimonas abortus sp. nov. is proposed, with the type strain
      UK34/07-5(T) ( = CIP 110303(T)  = CCUG 61094(T)  = DSM 24741(T)  = CCM 7941(T)).

PMID- 21724961
TI  - Evaluation of hospitalization for infections that are present on admission.
AB  - Hospitals have experienced increasing requirements for public reporting of
      various infection rates using clinical and administrative data. Until recently,
      such reports have not included analysis of "present on admission" (POA), an
      indicator designed to assess whether such infections are hospital acquired. The
      authors evaluated the frequency of the POA coding designation for 167 University
      HealthSystem Consortium hospitals for sepsis/septicemia (S-S), methicillin
      resistant Staphylococcus aureus (MRSA), and Clostridium difficile infection
      (CDI). The authors found that 70% of hospitalizations of patients with S-S, 86%
      of patients with MRSA, and 67% of patients with CDI had these conditions coded
      POA. The authors recommend that public reporting of hospital infection rates
      include POA status and that all health care organizations and providers should
      work more closely together to identify early and prevent such serious infections.

PMID- 21724962
TI  - Compression-dependent up-regulation of ephrin-A2 in PDL fibroblasts attenuates
      osteogenesis.
AB  - Members of the ephrin/Eph family have recently been shown to be involved in the
      regulation of bone homeostasis in a murine model. The activation of the EphB4
      receptor on osteoblasts by its ligand ephrin-B2 led to stimulation of
      osteoblastogenesis and therefore to bone formation. The activation of ephrin-A2
      EphA2 signaling on osteoblasts inhibited the activation of osteoblast-specific
      gene expression, leading to bone resorption. Fibroblasts within the periodontal
      ligament periodontal ligament may be one of the first responders to orthodontic
      forces. Periodontal ligament fibroblasts (PDLF) are mechanoresponsive. Members of
      the ephrin/Eph family might link mechanical forces received by PDLF with the
      regulation of osteoblastogenesis on osteoblasts of the alveolar bone. To study
      whether ephrin-A2 is modulated upon compression, we subjected human primary PDLF
      to static compressive forces (30.3 g/cm(2)). Static compressive forces
      significantly induced the expression of ephrin-A2, while the expression of ephrin
      B2 was significantly down-regulated. Moreover, osteoblasts of the alveolar bone
      stimulated with ephrin-A2 in vitro significantly suppressed their
      osteoblastogenic gene expression (RUNX2, ALPL) and decreased signs of
      osteoblastic differentiation, as demonstrated by a significantly reduced ALP
      activity. Together, these findings establish a role for this ligand/receptor
      system linking mechanical forces with the regulation of osteogenesis during
      orthodontic tooth movement.

PMID- 21724963
TI  - Impact of education campaign on community-based vector control in hastening the
      process of elimination of lymphatic filariasis in Tamil Nadu, South India.
AB  - Globally mosquito-borne lymphatic filariasis (LF) is targeted for elimination by
      2020. Towards this goal, the scope of community-based vector control as a
      supplementary strategy to mass drug administration (MDA) was assessed through an
      intensive education campaign and evaluated using pre- and post-educational
      surveys in an intervention and comparison village in Tamil Nadu, South India.
      Environmental and entomological indicators for breeding sites and mosquito
      density were examined before and after the intervention. Significant (P < 0.05)
      increase in knowledge was observed in intervention area with regard to
      transmission and control of LF. Relative change between intervention and
      comparison villages before and after intervention was also significant (z =
      >1.96). Multiple mosquito control and personal protection methods were in use
      during the post-intervention assessment and was evident from the significantly (P
      < 0.05) higher average score. Breeding sources declined significantly (P < 0.05)
      in the intervention village with a significant relative change (z = 4.32).
      Significant reduction in per man-hour indoor resting density of mosquitoes was
      observed in the intervention area compared to baseline. The per capita cost for
      reducing 87% of the mosquito density was $ 0.32 indicating the effectiveness of
      community-based approach. The usefulness of this strategy in the elimination of
      LF is discussed.

PMID- 21724964
TI  - Valuing the life experience of old adults and change in depressive symptoms:
      exploring an overlooked benefit of involvement in religion.
AB  - OBJECTIVE: Researchers argue that people may encounter difficulty finding
      productive roles in late life. The purpose of this study is to see whether older
      people who have found that fellow church members value their life experience
      encounter fewer symptoms of depression. METHODS: The data are from an ongoing
      nationwide survey (N = 501). RESULTS: Support is obtained for the following
      relationships: (a) Older people who go to church more often are more likely to
      feel fellow church members value their life experience, (b) having others value
      their life experience helps older people feel they belong in their congregation,
      (c) older individuals who feel they belong in their congregation are likely to
      have greater feelings of self-worth, and (d) greater self-worth is associated
      with a fewer symptoms of depression over time. DISCUSSION: The findings identify
      one way in which religion may help older people find a meaningful role to play in
      late life.

PMID- 21724965
TI  - Built environment and lower extremity physical performance: prospective findings
      from the study of osteoporotic fractures in women.
AB  - OBJECTIVE: We examined the association between walkability of the built
      environment and changes in physical performance among women aged 65 or older (n =
      1,671, 253 neighborhoods). METHOD: Street connectivity and street density,
      markers for neighborhood walkability, were assessed through linkage to secondary
      data sources. Physical performance was measured with timed-walk and chair-stand
      tests assessed during follow-up visits about every 2 years for 12 to 14 years.
      Multilevel models predicted change in physical performance, controlling for age,
      number of incident comorbidities, self-rated health, and death during follow-up.
      RESULTS: Overall, physical performance declined during follow-up (p < .001).
      Neighborhood walkability had no effect on change in physical performance among
      women who reported not walking at baseline. However, among women who walked,
      greater neighborhood walkability was associated with a slower decline in dynamic
      leg strength, indicated by score on chair stand. DISCUSSION: Neighborhood
      walkability may protect against decline in physical performance.

PMID- 21724966
TI  - Inhibition of neutrophil apoptosis via sphingolipid signaling in acute lung
      injury.
AB  - Acute lung injury (ALI) is characterized by lung inflammation and diffuse
      infiltration of neutrophils into the alveolar space. The inhibition of alveolar
      neutrophil apoptosis has been implicated in the pathogenesis of ALI. Although
      sphingolipids may regulate cell apoptosis, the role of sphingolipids in activated
      neutrophils during ALI is not clear. In this study, we test the hypothesis that
      sphingolipids would attenuate neutrophil apoptosis that contributes to the
      development of ALI. Lipopolysaccharide (LPS)-stimulated human neutrophils, with
      or without inhibitor treatment, were analyzed for apoptosis. We found that the
      inhibitory effect of LPS on neutrophil apoptosis was blocked by treatment with
      the neutral sphingomyelinase (nSMase) inhibitor sphingolactone-24 (Sph-24),
      sphingosine kinase inhibitor II, and p38 mitogen-activated protein kinase (MAPK)
      inhibitor 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5
      yl]pyridine (SB203580) but not by the acidic sphingomyelinase inhibitor
      chlorpromazine. LPS-activated phosphorylation of p38 MAPK also was attenuated by
      treatment with Sph-24 and sphingosine kinase inhibitor II. Furthermore, mice with
      LPS-induced lung injury were treated with the nSMase inhibitor Sph-24 to evaluate
      its impact on lung injury and survival. The severity of LPS-induced ALI was
      reduced, and the survival rate was increased in mice treated with Sph-24 compared
      with that in those given LPS alone. Intracellular levels of sphingolipids in
      alveolar neutrophils from patients with acute respiratory distress syndrome also
      were measured. We found that intracellular levels of ceramide and phospho-p38
      MAPK were elevated in alveolar neutrophils from acute respiratory distress
      syndrome patients. Our results demonstrate that activation of the
      nSMase/sphingosine-1-phosphate pathway to induce p38 MAPK phosphorylation results
      in inhibition of neutrophil apoptosis, which may contribute to the development of
      ALI.

PMID- 21724967
TI  - Grapheme-phoneme acquisition of deaf preschoolers.
AB  - We examined acquisition of grapheme-phoneme correspondences by 4 deaf and hard-of
      hearing preschoolers using instruction from a curriculum designed specifically
      for this population supplemented by Visual Phonics. Learning was documented
      through a multiple baseline across content design as well as descriptive
      analyses. Preschoolers who used sign language and had average to low-average
      receptive vocabulary skills and varied speech perception skills acquired all
      correspondences after instruction. They were also able to use that knowledge
      while reading words. On a posttest, the children were able to decode graphemes
      into corresponding phonemes and identified about half of the words that were
      included during instruction. However, they did not identify any novel words.
      Descriptive analyses suggest that the children used Visual Phonics as an
      effective mnemonic device to recall correspondences and that deaf and hard-of
      hearing preschoolers, even those with no speech perception abilities, benefited
      from explicit instruction in the grapheme-phoneme relationship using
      multimodality support.

PMID- 21724968
TI  - The genetically unstable dwarf locus in azuki bean (Vigna angularis (Willd.) Ohwi
      & Ohashi).
AB  - We characterized a spontaneous dwarf mutant showing extremely short internodes
      and dark green leaves originating from azuki bean (Vigna angularis (Willd.) Ohwi
      & Ohashi) cultivar "Erimo-shouzu." F(1) plants of 3 cross combinations between
      the dwarf mutant and several representative wild-type plants, Erimo-shouzu, V.
      angularis accession Acc2265 and wild relative V. riukiuensis accession Acc2482,
      supported the dwarf genotype being recessive. In a total of 3328 F(2) progeny of
      these 3 crosses, 65 dwarfs (2.0%) and 5 chimeric dwarfs (0.2%) segregated and the
      remainder were wild-type plants (97.8%). In F(3) progeny derived from self
      pollinated dwarf F(2) plants, we observed wild type (54.3%), dwarf (39.1%), and
      chimeric dwarf (6.5%) plants. Two types of chimeric plants were observed: dwarf
      branches on the axils of wild-type plant stems and wild-type branches on the
      axils of dwarf stems. In 21 dwarf F(2) plants, the dwarf trait cosegregated with
      simple sequence repeat marker CEDG154 on chromosome 4. Conversely, homozygote
      F(2) plants at this chromosomal segment from the dwarf mutant frequently (>90%)
      expressed the wild-type phenotype. We concluded that the dwarf phenotype is
      mitotically and meiotically inheritable and controlled by a single genetically
      unstable locus, designated Azuki Dwarf1 (AD1), which converts between 2
      phenotypic states bidirectionally.

PMID- 21724970
TI  - Finding the key to happy aging: a day reconstruction study of happiness.
AB  - OBJECTIVES: The main aim of this study was to examine the roles of physical
      passivity and extraversion in the relationship between daily engagement in
      activities and daily happiness among older adults. METHOD: A day reconstruction
      method was used to accurately examine day-to-day activities and happiness. In
      total, 438 participants completed a monthly electronic diary survey over a 2-year
      period, generating 79,181 reported activities and momentary happiness scores.
      RESULTS: The results show that happiness increases when older adults combine
      effortful social, physical, cognitive, and household activities with restful
      activities. Furthermore, participation in social activities mediated the direct
      relationship between extraversion and happiness. Also, individuals who score high
      on extraversion derive greater happiness from social activities compared with
      their low-extravert counterparts. CONCLUSIONS: The study extends activity theory
      by demonstrating that combining effortful activities with restful activities
      leads to greater happiness among older adults. Also, personality traits such as
      extraversion play a decisive role in the kind of activities that contribute most
      to daily happiness.

PMID- 21724971
TI  - Confronting moral pluralism in posttraditional Western societies: bioethics
      critically reassessed.
AB  - In the face of the moral pluralism that results from the death of God and the
      abandonment of a God's eye perspective in secular philosophy, bioethics arose in
      a context that renders it essentially incapable of giving answers to substantive
      moral questions, such as concerning the permissibility of abortion, human
      embryonic stem cell research, euthanasia, etc. Indeed, it is only when bioethics
      understands its own limitations and those of secular moral philosophy in general
      can it better appreciate those tasks that it can actually usefully perform in
      both the clinical and academic setting. It is the task of this paper to
      understand and reevaluate bioethics by understanding these limits. Academic
      bioethicists can analyze ideas, concepts, and claims necessary to understanding
      the moral questions raised in health care, assessing the arguments related to
      these issues, and provide an understanding of the different moral perspectives on
      bioethical issues. In the clinical setting, bioethicists can provide legal
      advice, serve as experts on IRBs, mediating disputes, facilitating decision
      making and risk management, and clarifying normative issues. However,
      understanding this is only possible when one understands the history, genesis,
      and foundations of bioethics and its inability to provide a resolution to
      postmodern moral pluralism.

PMID- 21724972
TI  - What is your guess? Lactescent plasma in acute leukemia.

PMID- 21724973
TI  - Whole-genome gene expression modifications associated with nitrosamine exposure
      and micronucleus frequency in human blood cells.
AB  - N-nitroso compounds (NOCs) are suspected human carcinogens and relevant in human
      exposure. NOCs also induce micronuclei (MN) formation in vivo. Since lymphocytic
      MN represent a validated biomarker of human cancer risk, establishing a link
      between NOC exposure and MN frequency in humans and concurrently investigating
      associated transcriptomic responses may provide crucial information on underlying
      molecular mechanisms that predispose to carcinogenicity. We used lymphocytes,
      from adult females participating in the pan-European biomarker research project
      NewGeneris, as a surrogate tissue for analysing such potentially carcinogenic
      gene expression and MN formation events in target organs. To assess NOC exposure,
      urine samples were analysed for marker nitrosamines. NOC excretion levels and MN
      frequency were subsequently linked to peripheral blood transcriptomics. We
      demonstrated a significant association between MN frequency and urinary NOCs (r =
      0.41, P = 0.025) and identified modifications in among others cytoskeleton
      remodeling, cell cycle, apoptosis and survival, signal transduction, immune
      response, G-protein signaling and development pathways, which indicate a response
      to NOC-induced genotoxicity. Moreover, we established a network of genes, the
      most important ones of which include FBXW7, BUB3, Caspase 2, Caspase 8, SMAD3,
      Huntingtin and MGMT, which are involved in processes relevant in carcinogenesis.
      The modified genetic processes and genes found in this study may be of interest
      for future investigations into the potential carcinogenic risk associated with
      NOC exposure in humans.

PMID- 21724974
TI  - Styrene exposure and risk of cancer.
AB  - Styrene is widely used in the manufacture of synthetic rubber, resins, polyesters
      and plastics. Styrene and the primary metabolite styrene-7,8-oxide are genotoxic
      and carcinogenic. Long-term chemical carcinogenesis bioassays showed that styrene
      caused lung cancers in several strains of mice and mammary cancers in rats and
      styrene-7,8-oxide caused tumours of the forestomach in rats and mice and of the
      liver in mice. Subsequent epidemiologic studies found styrene workers had
      increased mortality or incidences of lymphohematopoietic cancers (leukaemia or
      lymphoma or all), with suggestive evidence for pancreatic and esophageal tumours.
      No adequate human studies are available for styrene-7,8-oxide although this is
      the primary and active epoxide metabolite of styrene. Both are genotoxic and form
      DNA adducts in humans.

PMID- 21724975
TI  - Zebrafish obesogenic test: a tool for screening molecules that target adiposity.
AB  - Dietary and xenobiotic compounds may alter endocrine signaling and lipid
      homeostasis, thus inducing obesity. We describe a short-term assay method, the
      zebrafish obesogenic (ZO) test, for examining the effects of diet, drugs, and
      environmental contaminants, singly or in combination, on white adipose tissue
      (WAT) dynamics in live larvae. The ZO test is an intermediate step in obesity
      research, between in vitro and rodent assays, and may be also used to study the
      effect of environmental toxicants on the adiposity of aquatic species. The
      procedure, using Nile Red (NR) fluorescent probe to reveal adipocyte lipid
      droplets, is suitable for pharmaceutical or toxicological screening. Larvae
      treated at an environmentally-relevant concentration of tributyltin chloride
      (TBT), an environmental obesogen, exhibited a remarkable increase in adiposity,
      irrespective of the lipid composition of the background diet. Exogenous
      compounds, e.g., rosiglitazone or TBT, known to increase adiposity in the fasting
      state, were classified as obesogenic. Anti-obesogenic compounds favored a
      decrease in adiposity in the fasting state. The ZO test, using adipocyte lipid
      droplet size and adiposity as its endpoints, is a whole-organism alternative
      testing assay for obesogenic and anti-obesogenic compounds and mixtures and
      provides relevant information for environmental and human risk assessments.

PMID- 21724976
TI  - Neoplastic and nonneoplastic liver lesions induced by dimethylnitrosamine in
      Japanese medaka fish.
AB  - Small fish models have been used for decades in carcinogenicity testing.
      Demonstration of common morphological changes associated with specific mechanisms
      is a clear avenue by which data can be compared across divergent phyletic levels.
      Dimethylnitrosamine, used in rats to model human alcoholic cirrhosis and hepatic
      neoplasia, is also a potent hepatotoxin and carcinogen in fish. We recently
      reported some striking differences in the mutagenicity of DMN in lambda cII
      transgenic medaka fish vs. Big Blue((r)) rats, but the pre-neoplastic and
      neoplastic commonalities between the two models are largely unknown. Here, we
      focus on these commonalities, with special emphasis on the TGF-beta pathway and
      its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals,
      hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and
      "spindle cell" proliferation; hepatocellular and biliary carcinomas; and TGF
      beta1 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka.
      Positive TGF-beta1 staining increased with increasing DMN exposure in bile
      preductular epithelial cells, intermediate cells, immature hepatocytes and fewer
      mature hepatocytes. Muscle specific actin identified hepatic stellate cells in
      DMN-exposed fish. Additional mechanistic comparisons between animal models at
      different phyletic levels will continue to facilitate the interspecies
      extrapolations that are so critical to toxicological risk assessments.

PMID- 21724978
TI  - ABNM celebrates 40th anniversary.

PMID- 21724979
TI  - Outstanding JNM articles for 2010.

PMID- 21724982
TI  - Working together to move ahead.

PMID- 21724983
TI  - From the SNMTS president.

PMID- 21724984
TI  - Attenuation correction methods suitable for brain imaging with a PET/MRI scanner:
      a comparison of tissue atlas and template attenuation map approaches.
AB  - Modeled attenuation correction (AC) will be necessary for combined PET/MRI
      scanners not equipped with transmission scanning hardware. We compared 2 modeled
      AC approaches that use nonrigid registration with rotating (68)Ge rod-based
      measured AC for 10 subjects scanned with (18)F-FDG. METHODS: Two MRI and
      attenuation map pairs were evaluated: tissue atlas-based and measured templates.
      The tissue atlas approach used a composite of the BrainWeb and Zubal digital
      phantoms, whereas the measured templates were produced by averaging spatially
      normalized measured MR image and coregistered attenuation maps. The composite
      digital phantom was manually edited to include 2 additional tissue classes
      (paranasal sinuses, and ethmoidal air cells or nasal cavity). In addition, 3
      attenuation values for bone were compared. The MRI and attenuation map pairs were
      used to generate subject-specific attenuation maps via nonrigid registration of
      the MRI to the MR image of the subject. SPM2 and a B-spline free-form deformation
      algorithm were used for the nonrigid registration. To determine the accuracy of
      the modeled AC approaches, radioactivity concentration was assessed on a
      voxelwise and regional basis. RESULTS: The template approach produced better
      spatial consistency than the phantom-based atlas, with an average percentage
      error in radioactivity concentration across the regions, compared with measured
      AC, of -1.2% +/- 1.2% and -1.5% +/- 1.9% for B-spline and SPM2 registration,
      respectively. In comparison, the tissue atlas method with B-spline registration
      produced average percentage errors of 0.0% +/- 3.0%, 0.9% +/- 2.9%, and 2.9% +/-
      2.8% for bone attenuation values of 0.143 cm(-1), 0.152 cm(-1), and 0.172 cm(-1),
      respectively. The largest errors for the template AC method were found in parts
      of the frontal cortex (-3%) and the cerebellar vermis (-5%). Intersubject
      variability was higher with SPM2 than with B-spline. Compared with measured AC,
      template AC with B-spline and SPM2 achieved a correlation coefficient (R(2)) of
      0.99 and 0.98, respectively, for regional radioactivity concentration. The
      corresponding R(2) for the tissue atlas approach with B-spline registration was
      0.98, irrespective of the bone attenuation coefficient. CONCLUSION: Nonrigid
      registration of joint MRI and attenuation map templates can produce accurate AC
      for brain PET scans, particularly with measured templates and B-spline
      registration. Consequently, these methods are suitable for AC of brain scans
      acquired on combined PET/MRI systems.

PMID- 21724985
TI  - Cardiovascular nuclear imaging: balancing proven clinical value and potential
      radiation risk.

PMID- 21724986
TI  - Difference between restoring and predicting 3D structures of the loops in G
      protein-coupled receptors by molecular modeling.

PMID- 21724987
TI  - Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity
      transsynaptic receptor pair with signaling capabilities.
AB  - Latrophilin 1 (LPH1), a neuronal receptor of alpha-latrotoxin, is implicated in
      neurotransmitter release and control of presynaptic Ca(2+). As an "adhesion G
      protein-coupled receptor," LPH1 can convert cell surface interactions into
      intracellular signaling. To examine the physiological functions of LPH1, we used
      LPH1's extracellular domain to purify its endogenous ligand. A single protein of
      ~275 kDa was isolated from rat brain and termed Lasso. Peptide sequencing and
      molecular cloning have shown that Lasso is a splice variant of teneurin-2, a
      brain-specific orphan cell surface receptor with a function in neuronal
      pathfinding and synaptogenesis. We show that LPH1 and Lasso interact strongly and
      specifically. They are always copurified from rat brain extracts. Coculturing
      cells expressing LPH1 with cells expressing Lasso leads to their mutual
      attraction and formation of multiple junctions to which both proteins are
      recruited. Cells expressing LPH1 form chimerical synapses with hippocampal
      neurons in cocultures; LPH1 and postsynaptic neuronal protein PSD-95 accumulate
      on opposite sides of these structures. Immunoblotting and immunoelectron
      microscopy of purified synapses and immunostaining of cultured hippocampal
      neurons show that LPH1 and Lasso are enriched in synapses; in both systems, LPH1
      is presynaptic, whereas Lasso is postsynaptic. A C-terminal fragment of Lasso
      interacts with LPH1 and induces Ca(2+) signals in presynaptic boutons of
      hippocampal neurons and in neuroblastoma cells expressing LPH1. Thus, LPH1 and
      Lasso can form transsynaptic complexes capable of inducing presynaptic Ca(2+)
      signals, which might affect synaptic functions.

PMID- 21724991
TI  - Innate immune collectin surfactant protein D simultaneously binds both neutrophil
      extracellular traps and carbohydrate ligands and promotes bacterial trapping.
AB  - Neutrophils release DNA-based extracellular traps to capture and kill bacteria.
      The mechanism(s) and proteins that promote neutrophil extracellular trap (NET)
      mediated bacterial trapping are not clearly established. Surfactant protein D (SP
      D) is an innate immune collectin present in many mucosal surfaces. We
      hypothesized that SP-D can bind both the pathogens and NETs to augment NET
      mediated bacterial trapping. To test this hypothesis, we used LPS and Pseudomonas
      aeruginosa pneumonia mouse models and performed in vivo and ex vivo assays. In
      this study, we show that NETs are produced by the neutrophils recruited to the
      airways in response to the bacterial ligand. Notably, NETs are detected as short
      fragments of DNA-protein complexes in the airways as opposed to the long
      stringlike structures seen in ex vivo cultures. SP-D recognizes both the short
      NET fragments and the long NET DNA structures. SP-D-NET copurification studies
      further show that SP-D can simultaneously recognize NETs and carbohydrate ligands
      in vivo. Similar to the LPS model, soluble DNA-protein complexes and increased
      amounts of SP-D are detected in the murine model of P. aeruginosa pneumonia. We
      then tested the effect of SP-D on NET-mediated trapping of P. aeruginosa by means
      of Western blots, fluorescence microscopy, and scanning electron microscopy.
      Results of these experiments show that SP-D microagglutinates P. aeruginosa and
      allows an efficient bacterial trapping by NETs. Collectively, these findings
      provide a unique biological relevance for SP-D-DNA interactions and places SP-D
      as an important innate immune protein that promotes bacterial trapping by NETs
      during neutrophil-mediated host defense.

PMID- 21724990
TI  - The purinergic G protein-coupled receptor 6 inhibits effector T cell activation
      in allergic pulmonary inflammation.
AB  - We show that the P2Y(6) receptor, a purinergic G protein-coupled receptor with a
      high affinity for the nucleotide uridine diphosphate, is an important endogenous
      inhibitor of T cell function in allergic pulmonary inflammation. Mice
      conditionally deficient in P2Y(6) receptors [p2ry6 (flox/flox);cre/+ mice]
      exhibited severe airway and tissue pathology relative to P2Y(6)-sufficient [p2ry6
      (flox/flox)] littermates (+/+ mice) when treated intranasally with an extract of
      the dust mite Dermatophagoides farinae (Df). P2Y(6) receptors were inducibly
      expressed by lung, lymph node, and splenic CD4(+) and CD8(+) T cells of Df
      treated +/+ mice. Df-restimulated P2Y(6)-deficient lymph node cells produced
      higher levels of Th1 and Th2 cytokines, and polyclonally stimulated P2Y(6)
      deficient CD4(+) T cells proliferated faster than comparably stimulated P2Y(6)
      sufficient cells. The absence of P2Y(6) receptors on CD4(+) cells, but not APCs,
      was sufficient to amplify cytokine generation. Thus, P2Y(6) receptors protect the
      lung against exuberant allergen-induced pulmonary inflammation by inhibiting the
      activation of effector T cells.

PMID- 21724992
TI  - Bacteroides fragilis enterotoxin upregulates intercellular adhesion molecule-1 in
      endothelial cells via an aldose reductase-, MAPK-, and NF-kappaB-dependent
      pathway, leading to monocyte adhesion to endothelial cells.
AB  - Enterotoxigenic Bacteroides fragilis (ETBF) produces a ~ 20-kDa heat-labile
      enterotoxin (BFT) that plays an essential role in mucosal inflammation. Although
      a variety of inflammatory cells is found at ETBF-infected sites, little is known
      about leukocyte adhesion in response to BFT stimulation. We investigated whether
      BFT affected the expression of ICAM-1 and monocytic adhesion to endothelial cells
      (ECs). Stimulation of HUVECs and rat aortic ECs with BFT resulted in the
      induction of ICAM-1 expression. Upregulation of ICAM-1 was dependent on the
      activation of IkappaB kinase (IKK) and NF-kappaB signaling. In contrast,
      suppression of AP-1 did not affect ICAM-1 expression in BFT-stimulated cells.
      Suppression of NF-kappaB activity in HUVECs significantly reduced monocytic
      adhesion, indicating that ICAM-1 expression is indispensable for BFT-induced
      adhesion of monocytes to the endothelium. Inhibition of JNK resulted in a
      significant attenuation of BFT-induced ICAM-1 expression in ECs. Moreover,
      inhibition of aldose reductase significantly reduced JNK-dependent IKK/NF-kappaB
      activation, ICAM-1 expression, and adhesion of monocytes to HUVECs. These results
      suggest that a signaling pathway involving aldose reductase, JNK, IKK, and NF
      kappaB is required for ICAM-1 induction in ECs exposed to BFT, and may be
      involved in the leukocyte-adhesion cascade following infection with ETBF.

PMID- 21724993
TI  - Cutting edge: beta-catenin is dispensable for T cell effector differentiation,
      memory formation, and recall responses.
AB  - The molecular mechanisms that regulate mature T cell fate and enable cells to
      differentiate into memory T cells are largely unknown. Memory T cells share
      certain key features with stem cells: they both have the ability to self-renew
      and are long-lived. The Wnt-beta-catenin signaling pathway is a key player in
      regulating stem cell self-renewal and differentiation. We generated a conditional
      knockout mouse that specifically lacks beta-catenin in mature T cells and report
      in this article that beta-catenin is not involved in regulating effector versus
      memory T cell differentiation. beta-catenin-deficient memory T cells were
      phenotypically and functionally indistinguishable from control cells and made
      normal recall responses. beta-catenin deficiency does not affect T cell
      migration, T cell function in a model of chronic infection, or lymphopenia
      induced proliferation. Together, our data suggest that self-renewal and
      differentiation are regulated differently in memory T cells compared with
      epithelial and hematopoietic stem cells.

PMID- 21724994
TI  - The inhibiting Fc receptor for IgG, FcgammaRIIB, is a modifier of autoimmune
      susceptibility.
AB  - FcgammaRIIB-deficient mice generated in 129 background (FcgammaRIIB(129)(-/-)) if
      back-crossed into C57BL/6 background exhibit a hyperactive phenotype and develop
      lethal lupus. Both in mice and humans, the Fcgammar2b gene is located within a
      genomic interval on chromosome 1 associated with lupus susceptibility. In mice,
      the 129-derived haplotype of this interval, named Sle16, causes loss of self
      tolerance in the context of the B6 genome, hampering the analysis of the specific
      contribution of FcgammaRIIB deficiency to the development of lupus in
      FcgammaRIIB(129)(-/-) mice. Moreover, in humans genetic linkage studies revealed
      contradictory results regarding the association of "loss of function" mutations
      in the Fcgammar2b gene and susceptibility to systemic lupus erythematosis. In
      this study, we demonstrate that FcgammaRIIB(-/-) mice generated by gene targeting
      in B6-derived ES cells (FcgammaRIIB(B6)(-/-)), lacking the 129-derived flanking
      Sle16 region, exhibit a hyperactive phenotype but fail to develop lupus
      indicating that in FcgammaRIIB(129)(-/-) mice, not FcgammaRIIB deficiency but
      epistatic interactions between the C57BL/6 genome and the 129-derived Fcgammar2b
      flanking region cause loss of tolerance. The contribution to the development of
      autoimmune disease by the resulting autoreactive B cells is amplified by the
      absence of FcgammaRIIB, culminating in lethal lupus. In the presence of the Yaa
      lupus-susceptibility locus, FcgammaRIIB(B6)(-/-) mice do develop lethal lupus,
      confirming that FcgammaRIIB deficiency only amplifies spontaneous autoimmunity
      determined by other loci.

PMID- 21724995
TI  - Phospho-SXXE/D motif mediated TNF receptor 1-TRADD death domain complex formation
      for T cell activation and migration.
AB  - In TNF-treated cells, TNFR1, TNFR-associated death domain protein (TRADD), Fas
      associated death domain protein, and receptor-interacting protein kinase proteins
      form the signaling complex via modular interaction within their C-terminal death
      domains. In this paper, we report that the death domain SXXE/D motifs (i.e.,
      S381DHE motif of TNFR1-death domain as well as S215LKD and S296LAE motifs of
      TRADD-death domain) are phosphorylated, and this is required for stable TNFR1
      TRADD complex formation and subsequent activation of NF-kappaB. Phospho-S215LKD
      and phospho-S296LAE motifs are also critical to TRADD for recruiting Fas
      associated death domain protein and receptor-interacting protein kinase. IkappaB
      kinase beta plays a critical role in TNFR1 phosphorylation of S381, which leads
      to subsequent T cell migration and accumulation. Consistently, we observed in
      inflammatory bowel disease specimens that TNFR1 was constitutively phosphorylated
      on S381 in those inflammatory T cells, which had accumulated in high numbers in
      the inflamed mucosa. Therefore, SXXE/D motifs found in the cytoplasmic domains of
      many TNFR family members and their adaptor proteins may serve to function as a
      specific interaction module for the alpha-helical death domain signal
      transduction.

PMID- 21724996
TI  - Omega-3 fatty acid-derived mediators 17(R)-hydroxy docosahexaenoic acid, aspirin
      triggered resolvin D1 and resolvin D2 prevent experimental colitis in mice.
AB  - Resolvins of the D series are generated from docosahexaenoic acid, which are
      enriched in fish oils and are believed to exert beneficial roles on diverse
      inflammatory disorders, including inflammatory bowel disease (IBD). In this
      study, we investigated the anti-inflammatory effects of the aspirin-triggered
      resolvin D1 (AT-RvD1), its precursor (17(R)-hydroxy docosahexaenoic acid [17R
      HDHA]) and resolvin D2 (RvD2) in dextran sulfate sodium (DSS)- or 2,4,6
      trinitrobenzene sulfonic acid-induced colitis. Our results showed that the
      systemic treatment with AT-RvD1, RvD2, or 17R-HDHA in a nanogram range greatly
      improved disease activity index, body weight loss, colonic damage, and
      polymorphonuclear infiltration in both colitis experimental models. Moreover,
      these treatments reduced colonic cytokine levels for TNF-alpha, IL-1beta, MIP-2,
      and CXCL1/KC, as well as mRNA expression of NF-kappaB and the adhesion molecules
      VCAM-1, ICAM-1, and LFA-1. Furthermore, AT-RvD1, but not RvD2 or 17R-HDHA,
      depended on lipoxin A4 receptor (ALX) activation to inhibit IL-6, MCP-1, IFN
      gamma, and TNF-alpha levels in bone marrow-derived macrophages stimulated with
      LPS. Similarly, ALX blockade reversed the beneficial effects of AT-RvD1 in DSS
      induced colitis. To our knowledge, our findings showed for the first time the
      anti-inflammatory effects of resolvins of the D series and precursor 17R-HDHA in
      preventing experimental colitis. We also demonstrated the relevant role exerted
      by ALX activation on proresolving action of AT-RvD1. Moreover, AT-RvD1 showed a
      higher potency than 17R-HDHA and RvD2 in preventing DSS-induced colitis. The
      results suggest that these lipid mediators possess a greater efficacy when
      compared with other currently used IBD therapies, such as monoclonal anti-TNF,
      and have the potential to be used for treating IBD.

PMID- 21724997
TI  - Protective roles for fibrin, tissue factor, plasminogen activator inhibitor-1,
      and thrombin activatable fibrinolysis inhibitor, but not factor XI, during
      defense against the gram-negative bacterium Yersinia enterocolitica.
AB  - Septic infections dysregulate hemostatic pathways, prompting coagulopathy.
      Nevertheless, anticoagulant therapies typically fail to protect humans from
      septic pathology. The data reported in this work may help to explain this
      discrepancy by demonstrating critical protective roles for coagulation leading to
      fibrin deposition during host defense against the Gram-negative bacterium
      Yersinia enterocolitica. After i.p. inoculation with Y. enterocolitica,
      fibrinogen-deficient mice display impaired cytokine and chemokine production in
      the peritoneal cavity and suppressed neutrophil recruitment. Moreover, both gene
      targeted fibrinogen-deficient mice and wild-type mice treated with the
      anticoagulant coumadin display increased hepatic bacterial burden and mortality
      following either i.p. or i.v. inoculation with Y. enterocolitica. Mice with low
      tissue factor activity succumb to yersiniosis with a phenotype similar to
      fibrin(ogen)-deficient mice, whereas factor XI-deficient mice show wild-type
      levels of resistance. Mice deficient in plasminogen activator inhibitor-1 or
      thrombin-activatable fibrinolysis inhibitor display modest phenotypes, but mice
      deficient in both plasminogen activator inhibitor-1 and thrombin-activatable
      fibrinolysis inhibitor succumb to yersiniosis with a phenotype resembling
      fibrin(ogen)-deficient mice. These findings demonstrate critical protective roles
      for the tissue factor-dependent extrinsic coagulation pathway during host defense
      against bacteria and caution that therapeutics targeting major thrombin
      generating or antifibrinolytic pathways may disrupt fibrin-mediated host defense
      during Gram-negative sepsis.

PMID- 21724998
TI  - The rhodanese domain of ThiI is both necessary and sufficient for synthesis of
      the thiazole moiety of thiamine in Salmonella enterica.
AB  - In Salmonella enterica, ThiI is a bifunctional enzyme required for the synthesis
      of both the 4-thiouridine modification in tRNA and the thiazole moiety of
      thiamine. In 4-thiouridine biosynthesis, ThiI adenylates the tRNA uridine and
      transfers sulfur from a persulfide formed on the protein. The role of ThiI in
      thiazole synthesis is not yet well understood. Mutational analysis described here
      found that ThiI residues required for 4-thiouridine synthesis were not involved
      in thiazole biosynthesis. The data further showed that the C-terminal rhodanese
      domain of ThiI was sufficient for thiazole synthesis in vivo. Together, these
      data support the conclusion that sulfur mobilization in thiazole synthesis is
      mechanistically distinct from that in 4-thiouridine synthesis and suggest that
      functional annotation of ThiI in genome sequences should be readdressed.
      Nutritional studies described here identified an additional cysteine-dependent
      mechanism for sulfur mobilization to thiazole that did not require ThiI, IscS,
      SufS, or glutathione. The latter mechanism may provide insights into the
      chemistry used for sulfur mobilization to thiazole in organisms that do not
      utilize ThiI.

PMID- 21724999
TI  - Transcriptional profiling of nitrogen fixation in Azotobacter vinelandii.
AB  - Most biological nitrogen (N(2)) fixation results from the activity of a
      molybdenum-dependent nitrogenase, a complex iron-sulfur enzyme found associated
      with a diversity of bacteria and some methanogenic archaea. Azotobacter
      vinelandii, an obligate aerobe, fixes nitrogen via the oxygen-sensitive Mo
      nitrogenase but is also able to fix nitrogen through the activities of
      genetically distinct alternative forms of nitrogenase designated the Vnf and Anf
      systems when Mo is limiting. The Vnf system appears to replace Mo with V, and the
      Anf system is thought to contain Fe as the only transition metal within the
      respective active site metallocofactors. Prior genetic analyses suggest that a
      number of nif-encoded components are involved in the Vnf and Anf systems. Genome
      wide transcription profiling of A. vinelandii cultured under nitrogen-fixing
      conditions under various metal amendments (e.g., Mo or V) revealed the discrete
      complement of genes associated with each nitrogenase system and the extent of
      cross talk between the systems. In addition, changes in transcript levels of
      genes not directly involved in N(2) fixation provided insight into the
      integration of central metabolic processes and the oxygen-sensitive process of
      N(2) fixation in this obligate aerobe. The results underscored significant
      differences between Mo-dependent and Mo-independent diazotrophic growth that
      highlight the significant advantages of diazotrophic growth in the presence of
      Mo.

PMID- 21725000
TI  - A novel testosterone catabolic pathway in bacteria.
AB  - Forty years ago, Coulter and Talalay (A. W. Coulter and P. Talalay, J. Biol.
      Chem. 243:3238-3247, 1968) established the oxygenase-dependent pathway for the
      degradation of testosterone by aerobes. The oxic testosterone catabolic pathway
      involves several oxygen-dependent reactions and is not available for anaerobes.
      Since then, a variety of anaerobic bacteria have been described for the ability
      to degrade testosterone in the absence of oxygen. Here, a novel, oxygenase
      independent testosterone catabolic pathway in such organisms is described.
      Steroidobacter denitrificans DSMZ18526 was shown to be capable of degrading
      testosterone in the absence of oxygen and was selected as the model organism in
      this study. In a previous investigation, we identified the initial intermediates
      involved in an anoxic testosterone catabolic pathway, most of which are identical
      to those of the oxic pathway demonstrated in Comamonas testosteroni. In this
      study, five additional intermediates of the anoxic pathway were identified. We
      demonstrated that subsequent steps of the anoxic pathway greatly differ from
      those of the established oxic pathway, which suggests that a novel pathway for
      testosterone catabolism is present. In the proposed anoxic pathway, a reduction
      reaction occurs at C-4 and C-5 of androsta-1,4-diene-3,17-dione, the last common
      intermediate of both the oxic and anoxic pathways. After that, a novel hydration
      reaction occurs and a hydroxyl group is thus introduced to the C-1alpha position
      of C(19)steroid substrates. To our knowledge, an enzymatic hydration reaction
      occurring at the A ring of steroid compounds has not been reported before.

PMID- 21725001
TI  - Regulated shift from helical to polar localization of Listeria monocytogenes cell
      wall-anchored proteins.
AB  - Many virulence factors of Gram-positive bacterial pathogens are covalently
      anchored to the peptidoglycan (PG) by sortase enzymes. However, for rod-shaped
      bacteria little is known about the spatiotemporal organization of these surface
      proteins in the cell wall. Here we report the three-dimensional (3D) localization
      of the PG-bound virulence factors InlA, InlH, InlJ, and SvpA in the envelope of
      Listeria monocytogenes under different growth conditions. We found that all PG
      anchored proteins are positioned along the lateral cell wall in nonoverlapping
      helices. However, these surface proteins can also become localized at the pole
      and asymmetrically distributed when specific regulatory pathways are activated.
      InlA and InlJ are enriched at poles when expressed at high levels in exponential
      phase bacteria. InlA and InlH, which are sigma(B)dependent, specifically
      relocalize to the septal cell wall and subsequently to the new pole in cells
      entering stationary phase. The accumulation of InlA and InlH in the septal region
      also occurs when oxidative stress impairs bacterial growth. In contrast, the iron
      dependent protein SvpA is present at the old pole and is excluded from the septum
      and new pole of bacteria grown under low-iron conditions. We conclude that L.
      monocytogenes rapidly reorganizes the spatial localization of its PG proteins in
      response to changes in environmental conditions such as nutrient deprivation or
      other stresses. This dynamic control would distribute virulence factors at
      specific sites during the infectious process.

PMID- 21725002
TI  - Phenylacetyl coenzyme A is an effector molecule of the TetR family
      transcriptional repressor PaaR from Thermus thermophilus HB8.
AB  - Phenylacetic acid (PAA) is a common intermediate in the catabolic pathways of
      several structurally related aromatic compounds. It is converted into
      phenylacetyl coenzyme A (PA-CoA), which is degraded to general metabolites by a
      set of enzymes. Within the genome of the extremely thermophilic bacterium Thermus
      thermophilus HB8, a cluster of genes, including a TetR family transcriptional
      regulator, may be involved in PAA degradation. The gene product, which we named
      T. thermophilus PaaR, negatively regulated the expression of the two operons
      composing the gene cluster in vitro. T. thermophilus PaaR repressed the target
      gene expression by binding pseudopalindromic sequences, with a consensus sequence
      of 5'-CNAACGNNCGTTNG-3', surrounding the promoters. PA-CoA is a ligand of PaaR,
      with a proposed binding stoichiometry of 1:1 protein monomer, and was effective
      for transcriptional derepression. Thus, PaaR is a functional homolog of PaaX, a
      GntR transcriptional repressor found in Escherichia coli and Pseudomonas strains.
      A three-dimensional structure of T. thermophilus PaaR was predicted by homology
      modeling. In the putative structure, PaaR adopts the typical three-dimensional
      structure of the TetR family proteins, with 10 alpha-helices. A positively
      charged surface at the center of the molecule is similar to the acyl-CoA-binding
      site of another TetR family transcriptional regulator, T. thermophilus FadR,
      which is involved in fatty acid degradation. The CoA moiety of PA-CoA may bind to
      the center of the PaaR molecule, in a manner similar to the binding of the CoA
      moiety of acyl-CoA to FadR.

PMID- 21725003
TI  - The sulfolobicin genes of Sulfolobus acidocaldarius encode novel antimicrobial
      proteins.
AB  - Crenarchaea, such as Sulfolobus acidocaldarius and Sulfolobus tokodaii, produce
      antimicrobial proteins called sulfolobicins. These antimicrobial proteins inhibit
      the growth of closely related species. Here we report the identification of the
      sulfolobicin-encoding genes in S. acidocaldarius. The active sulfolobicin
      comprises two proteins that are equipped with a classical signal sequence. These
      proteins are secreted by the cells and found to be membrane vesicle associated.
      Gene inactivation studies demonstrate that both proteins are required for the
      bacteriostatic antimicrobial activity. Sulfolobicins constitute a novel class of
      antimicrobial proteins without detectable homology to any other protein.

PMID- 21725004
TI  - Bile salts induce resistance to polymyxin in enterohemorrhagic Escherichia coli
      O157:H7.
AB  - Many enteric bacteria use bile as an environmental cue to signal resistance and
      virulence gene expression. Microarray analysis of enterohemorrhagic Escherichia
      coli O157:H7 (EHEC) treated with bile salts revealed upregulation of genes for an
      efflux system (acrAB), a two-component signal transduction system (basRS/pmrAB),
      and lipid A modification (arnBCADTEF and ugd). Bile salt treatment of EHEC
      produced a basS- and arnT-dependent resistance to polymyxin.

PMID- 21725005
TI  - Identification of a chemoreceptor zinc-binding domain common to cytoplasmic
      bacterial chemoreceptors.
AB  - We report the identification and characterization of a previously unidentified
      protein domain found in bacterial chemoreceptors and other bacterial signal
      transduction proteins. This domain contains a motif of three noncontiguous
      histidines and one cysteine, arranged as Hxx[WFYL]x(21-28)Cx[LFMVI]Gx[WFLVI]x(18
      27)HxxxH(boldface type indicates residues that are nearly 100% conserved). This
      domain was first identified in the soluble Helicobacter pylori chemoreceptor
      TlpD. Using inductively coupled plasma mass spectrometry on heterologously and
      natively expressed TlpD, we determined that this domain binds zinc with a
      subfemtomolar dissociation constant. We thus named the domain CZB, for
      chemoreceptor zinc binding. Further analysis showed that many bacterial signaling
      proteins contain the CZB domain, most commonly proteins that participate in
      chemotaxis but also those that participate in c-di-GMP signaling and
      nitrate/nitrite sensing, among others. Proteins bearing the CZB domain are found
      in several bacterial phyla. The variety of signaling proteins using the CZB
      domain suggests that it plays a critical role in several signal transduction
      pathways.

PMID- 21725006
TI  - Genome sequence of the ethanol-producing Zymomonas mobilis subsp. mobilis
      lectotype strain ATCC 10988.
AB  - Zymomonas mobilis ATCC 10988 is the type strain of the Z. mobilis subsp. mobilis
      taxon, members of which are some of the most rigorous ethanol-producing bacteria.
      Isolated from Agave cactus fermentations in Mexico, ATCC 10988 is one of the
      first Z. mobilis strains to be described and studied. Its robustness in sucrose
      substrate fermentations, physiological characteristics, large number of plasmids,
      and overall genomic plasticity render this strain important to the study of the
      species. Here we report the finishing and annotation of the ATCC 10988
      chromosomal and plasmid genome.

PMID- 21725007
TI  - Synergism between different germinant receptors in the germination of Bacillus
      subtilis spores.
AB  - Rates of commitment to germinate and germination of Bacillus subtilis spores with
      mixtures of low concentrations of germinants acting on different germinant
      receptors (GRs) were much higher than the sums of the rates of commitment and
      germination with individual germinants alone. This synergism with mixtures of
      nutrient germinants was not seen with spores lacking GRs responsible for
      recognizing one or several components of the germinant mixtures and was not
      eliminated by either a gerD mutation or overexpression of one of the GRs involved
      in this synergism. This synergism was also not seen between the germinant L
      valine, which acts via a GR, and the germinant dodecylamine, which does not act
      via any GR. These results indicate that spores not only integrate but can also
      amplify signals from multiple germinants and multiple GRs in determining rates of
      commitment and overall spore germination. This amplification can be explained by
      a simple mechanism in which a single signal integrator triggers germination above
      an accumulation threshold. Direct cooperative action between GRs may further add
      to the synergism seen in germination triggered by multiple GRs. Further
      experiments and modeling are required to determine the relative contributions of
      these different mechanisms.

PMID- 21725008
TI  - Differential accumulation of nif structural gene mRNA in Azotobacter vinelandii.
AB  - Northern analysis was employed to investigate mRNA produced by mutant strains of
      Azotobacter vinelandii with defined deletions in the nif structural genes and in
      the intergenic noncoding regions. The results indicate that intergenic RNA
      secondary structures effect the differential accumulation of transcripts,
      supporting the high Fe protein-to-MoFe protein ratio required for optimal
      diazotrophic growth.

PMID- 21725009
TI  - Genome sequence of the 1,4-dioxane-degrading Pseudonocardia dioxanivorans strain
      CB1190.
AB  - Pseudonocardia dioxanivorans CB1190 is the first bacterium reported to be capable
      of growth on the environmental contaminant 1,4-dioxane and the first member of
      the genus Pseudonocardia for which there is an annotated genome sequence.
      Preliminary analysis of the genome (chromosome and three plasmids) indicates that
      strain CB1190 possesses several multicomponent monooxygenases that could be
      involved in the aerobic degradation of 1,4-dioxane and other environmental
      contaminants.

PMID- 21725010
TI  - Activity and transcriptional regulation of bacterial protein-like glycerol-3
      phosphate dehydrogenase of the haloarchaea in Haloferax volcanii.
AB  - Glycerol is a primary energy source for heterotrophic haloarchaea and a major
      component of "salty" biodiesel waste. Glycerol is catabolized solely by glycerol
      kinase (encoded by glpK) to glycerol-3-phosphate (G3P) in Haloferax volcanii.
      Here we characterized the next critical step of this metabolic pathway: the
      conversion of G3P to dihydroxyacetone phosphate by G3P dehydrogenase (G3PDH). H.
      volcanii harbors two putative G3PDH operons: (i) glpA1B1C1, located on the
      chromosome within the neighborhood of glpK, and (ii) glpA2B2C2, on megaplasmid
      pHV4. Analysis of knockout strains revealed that glpA1(and not glpA2) is required
      for growth on glycerol. However, both glpA1 and glpA2 could complement a glpA1
      knockout strain (when expressed from a strong promoter in trans) and were
      required for the total G3PDH activity of cell lysates. The glpA1B1C1, glpK,
      glpF(encoding a putative glycerol facilitator), and ptsH2(encoding a homolog of
      the bacterial phosphotransferase system protein Hpr) genes were transcriptionally
      linked and appeared to be under the control of a strong, G3P-inducible promoter
      upstream of glpA1. Overall, this study provides fundamental insights into
      glycerol metabolism in H. volcanii and enhances our understanding of central
      metabolic pathways of haloarchaea.

PMID- 21725011
TI  - The sigmaB-dependent yabJ-spoVG operon is involved in the regulation of
      extracellular nuclease, lipase, and protease expression in Staphylococcus aureus.
AB  - The alternative sigma factor sigma(B) of Staphylococcus aureus is involved in the
      coordination of the general stress response, expression of virulence
      determinants, and modulation of antibiotic resistance levels. It controls a large
      regulon, either directly by recognizing conserved sigma(B) promoter sequences or
      indirectly via sigma(B)-dependent elements. The sigma(B)-controlled yabJ-spoVG
      operon encodes two such putative downstream elements. We report here
      transcriptome analysis in S. aureus Newman, showing that inactivation of the yabJ
      spoVG operon had primarily a repressing effect on a small subregulon encoding
      mainly virulence factors, including a nuclease (nuc), a protease (splE) and a
      lipase (lip). As a consequence, extracellular nuclease, protease, and lipase
      activities were reduced in a DeltayabJ-spoVG mutant. trans-complementation by
      SpoVG was sufficient to restore their reduced phenotypic expression and lowered
      transcription due to the yabJ-spoVG deletion. It did not restore, however, the
      changes triggered by sigma(B) inactivation, indicating that both regulons only
      partially overlap, despite the sigma(B) dependency of the yabJ-spoVG expression.
      Thus, sigma(B) is likely to control additional, SpoVG-independent factors
      affecting the expression of numerous hydrolytic enzymes. SpoVG, on the other
      hand, seems to fine-tune the sigma(B)-dependent regulation of a subset of
      virulence factors by antagonizing the sigma(B) effect.

PMID- 21725012
TI  - Identification of C(4)-dicarboxylate transport systems in Pseudomonas aeruginosa
      PAO1.
AB  - Pseudomonas aeruginosa utilizes preferentially C(4)-dicarboxylates such as
      malate, fumarate, and succinate as carbon and energy sources. We have identified
      and characterized two C(4)-dicarboxylate transport (Dct) systems in P. aeruginosa
      PAO1. Inactivation of the dctA(PA1183) gene caused a growth defect of the strain
      in minimal media supplemented with succinate, fumarate or malate, indicating that
      DctA has a major role in Dct. However, residual growth of the dctA mutant in
      these media suggested the presence of additional C(4)-dicarboxylate
      transporter(s). Tn5 insertion mutagenesis of the DeltadctA mutant led to the
      identification of a second Dct system, i.e., the DctPQM transporter belonging to
      the tripartite ATP-independent periplasmic (TRAP) family of carriers. The
      DeltadctA DeltadctPQM double mutant showed no growth on malate and fumarate and
      residual growth on succinate, suggesting that DctA and DctPQM are the only malate
      and fumarate transporters, whereas additional transporters for succinate are
      present. Using lacZ reporter fusions, we showed that the expression of the dctA
      gene and the dctPQM operon was enhanced in early exponential growth phase and
      induced by C(4)-dicarboxylates. Competition experiments demonstrated that the
      DctPQM carrier was more efficient than the DctA carrier for the utilization of
      succinate at micromolar concentrations, whereas DctA was the major transporter at
      millimolar concentrations. To conclude, this is the first time that the high- and
      low-affinity uptake systems for succinate DctA and DctPQM have been reported to
      function coordinately to transport C(4)-dicarboxylates and that the alternative
      sigma factor RpoN and a DctB/DctD two-component system regulates simultaneously
      the dctA gene and the dctPQM operon.

PMID- 21725013
TI  - A novel toxin regulator, the CPE1446-CPE1447 protein heteromeric complex,
      controls toxin genes in Clostridium perfringens.
AB  - Clostridium perfringens is a Gram-positive anaerobic spore-forming bacterium that
      is widespread in environmental soil and sewage, as well as in animal intestines.
      It is also a causative agent of diseases in humans and other animals, and it
      produces numerous extracellular enzymes and toxins. Although these toxins have
      been characterized in detail, regulators of toxin genes are less well understood.
      The present study identified CPE1447 and CPE1446 as novel regulators of toxin
      gene expression. CPE1447 and CPE1446 are cotranscribed as an operon, and the
      encoded proteins have a helix-turn-helix (HTH) motif at the N termini of their
      amino acid sequences, suggesting that CPE1447 and CPE1446 control the target
      genes as transcriptional regulators. The expression of several genes encoding
      toxins was changed in both a CPE1446 mutant and a CPE1447-CPE1446 deletion
      mutant. Complementation of CPE1446 and CPE1447 revealed that CPE1447 and CPE1446
      coordinately regulate their target genes. CPE1447 protein was coprecipitated with
      His-tagged CPE1446 protein, indicating that the CPE1447 and CPE1446 proteins form
      a stable complex in C. perfringens under their native conditions. Although the
      small RNA that regulates several genes under the VirR/VirS two-component system
      (VR-RNA) positively affected CPE1447-CPE1446 mRNA expression, it did not control
      expression of the CPE1447-CPE1446 regulon, demonstrating that CPE1447 and CPE1446
      regulate a different set of toxin genes from the VirR/VirS-VR-RNA cascade.

PMID- 21725014
TI  - A specialized aspartokinase enhances the biosynthesis of the osmoprotectants
      ectoine and hydroxyectoine in Pseudomonas stutzeri A1501.
AB  - The compatible solutes ectoine and hydroxyectoine are widely produced by bacteria
      as protectants against osmotic and temperature stress. l-Aspartate-beta
      semialdehyde is used as the precursor molecule for ectoine/hydroxyectoine
      biosynthesis that is catalyzed by the EctABCD enzymes. l-Aspartate-beta
      semialdehyde is a central intermediate in different biosynthetic pathways and is
      produced from l-aspartate by aspartokinase (Ask) and aspartate-semialdehyde
      dehydrogenase (Asd). Ask activity is typically stringently regulated by
      allosteric control to avoid gratuitous synthesis of aspartylphosphate. Many
      organisms have evolved multiple forms of aspartokinase, and feedback regulation
      of these specialized Ask enzymes is often adapted to the cognate biochemical
      pathways. The ectoine/hydroxyectoine biosynthetic genes (ectABCD) are followed in
      a considerable number of microorganisms by an askgene (ask_ect), suggesting that
      Ask_Ect is a specialized enzyme for this osmoadaptive biosynthetic pathway.
      However, none of these Ask_Ect enzymes have been functionally characterized.
      Pseudomonas stutzeri A1501 synthesizes both ectoine and hydroxyectoine in
      response to increased salinity, and it possesses two Ask enzymes: Ask_Lys and
      Ask_Ect. We purified both Ask enzymes and found significant differences with
      regard to their allosteric control: Ask_LysC was inhibited by threonine and in a
      concerted fashion by threonine and lysine, whereas Ask_Ect showed inhibition only
      by threonine. The ectABCD_askgenes from P. stutzeri A1501 were cloned and
      functionally expressed in Escherichia coli, and this led to osmostress
      protection. An E. colistrain carrying the plasmid-based ectABCD_askgene cluster
      produced significantly more ectoine/hydroxyectoine than a strain expressing the
      ectABCDgene cluster alone. This finding suggests a specialized role for Ask_Ect
      in ectoine/hydroxyectoine biosynthesis.

PMID- 21725015
TI  - Draft genome sequence of the novel agar-digesting marine bacterium HQM9.
AB  - Strain HQM9, an aerobic, rod-shaped marine bacterium from red algae, can produce
      agarases and liquefy solid plating media efficiently when agar is used as a
      coagulant. Here we report the draft genome sequence and the initial findings from
      a preliminary analysis of strain HQM9, which should be a novel species of
      Flavobacteriaceae.

PMID- 21725016
TI  - Autotrophic methanotrophy in verrucomicrobia: Methylacidiphilum fumariolicum SolV
      uses the Calvin-Benson-Bassham cycle for carbon dioxide fixation.
AB  - Genome data of the extreme acidophilic verrucomicrobial methanotroph
      Methylacidiphilum fumariolicumstrain SolV indicated the ability of autotrophic
      growth. This was further validated by transcriptome analysis, which showed that
      all genes required for a functional Calvin-Benson-Bassham (CBB) cycle were
      transcribed. Experiments with (13)CH(4) or (13)CO(2) in batch and chemostat
      cultures demonstrated that CO(2) is the sole carbon source for growth of strain
      SolV. In the presence of CH(4), CO(2) concentrations in the headspace below 1%
      (vol/vol) were growth limiting, and no growth was observed when
      CO(2)concentrations were below 0.3% (vol/vol). The activity of the key enzyme of
      the CBB cycle, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO),
      measured with a (13)C stable-isotope method was about 70 nmol CO(2) fixed . min(
      1). mg of protein(-1). An immune reaction with antibody against the large subunit
      of RuBisCO on Western blots was found only in the supernatant fractions of cell
      extracts. The apparent native mass of the RuBisCO complex in strain SolV was
      about 482 kDa, probably consisting of 8 large (53-kDa) and 8 small (16-kDa)
      subunits. Based on phylogenetic analysis of the corresponding RuBisCO gene, we
      postulate that RuBisCO of the verrucomicrobial methanotrophs represents a new
      type of form I RuBisCO.

PMID- 21725017
TI  - CT406 encodes a chlamydial ortholog of NrdR, a repressor of ribonucleotide
      reductase.
AB  - Chlamydia trachomatis is an obligate intracellular bacterium that is dependent on
      its host cell for nucleotides. Chlamydia imports ribonucleotide triphosphates
      (NTPs) but not deoxyribonucleotide triphosphates (dNTPs) and instead uses
      ribonucleotide reductase to convert imported ribonucleotides into
      deoxyribonucleotides for DNA synthesis. The genes encoding ribonucleotide
      reductase have been recently shown to be negatively controlled by a conserved
      regulator called NrdR. In this study, we provide direct evidence that Escherichia
      coli NrdR is a transcriptional repressor and that C. trachomatis CT406 encodes
      its chlamydial ortholog. We showed that CT406 binds specifically to two NrdR
      boxes upstream of the nrdAB operon in C. trachomatis. Using an in vitro
      transcription assay, we confirmed that these NrdR boxes function as an operator
      since they were necessary and sufficient for CT406-mediated repression. We
      validated our in vitro findings with reporter studies in E. coli showing that
      both E. coli NrdR and CT406 repressed transcription from the E. coli nrdH and C.
      trachomatis nrdAB promoters in vivo. This in vivo repression was reversed by
      hydroxyurea treatment. Since hydroxyurea inhibits ribonucleotide reductase and
      reduces intracellular deoxyribonucleotide levels, these results suggest that NrdR
      activity is modulated by a deoxyribonucleotide corepressor.

PMID- 21725018
TI  - An ABC-type cobalt transport system is essential for growth of Sinorhizobium
      meliloti at trace metal concentrations.
AB  - We report expression and mutant phenotypes for a gene cluster in Sinorhizobium
      meliloti, designated cbtJKL, that has been shown to encode an ABC-type cobalt
      transport system. Transcription of cbtJKL initiated 384 nucleotides upstream from
      the cbtJ translation start codon, and the resulting 5' region contained a
      putative B(12)riboswitch. Expression of the cbtJKL genes appeared to be
      controlled by (cobalt-loaded) cobalamin interacting at the B(12)riboswitch, since
      (i) a putative B(12)riboswitch was located within this large upstream region,
      (ii) cbtJ transcription was repressed upon addition of cobalt or vitamin B(12),
      and (iii) deletions in the B(12)riboswitch resulted in constitutive cbtJKL
      transcription. Insertion mutants in cbtJKL failed to grow in LB medium, and
      growth was restored through the addition of cobalt but not other metals. This
      growth phenotype appeared to be due to the chelation of cobalt present in LB, and
      cbtJKL mutants also failed to grow in minimal medium containing the chelating
      agent EDTA unless the medium was supplemented with additional or excess cobalt.
      In uptake experiments, (57)Co(2+)accumulation was high in wild-type cells
      expressing the cbtJKL genes, whereas wild-type cells in which cbtJKL expression
      was repressed showed reduced accumulation. In cbtJKL mutant cells,
      (57)Co(2+)accumulation was reduced relative to that of the wild type, and
      presumably, this residual cobalt transport occurred via an alternate ion uptake
      system(s) that is not specific to cobalt. In symbiosis, the alternate system(s)
      appeared to mediate cobalt transport into bacteroid cells, as low cbtJKL
      expression was detected in bacteroids and cbtJKL mutants formed N(2)-fixing
      nodules on alfalfa.

PMID- 21725019
TI  - UvrD2 is essential in Mycobacterium tuberculosis, but its helicase activity is
      not required.
AB  - UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in
      bacteria. Mycobacterium tuberculosis has two annotated UvrD homologues; here we
      investigate the role of UvrD2. The uvrD2 gene at its native locus could be
      knocked out only in the presence of a second copy of the gene, demonstrating that
      uvrD2 is essential. Analysis of the putative protein domain structure of UvrD2
      shows a distinctive domain architecture, with an extended C terminus containing
      an HRDC domain normally found in SF2 family helicases and a linking domain
      carrying a tetracysteine motif. Truncated constructs lacking the C-terminal
      domains of UvrD2 were able to compensate for the loss of the chromosomal copy,
      showing that these C-terminal domains are not essential. Although UvrD2 is a
      functional helicase, a mutant form of the protein lacking helicase activity was
      able to permit deletion of uvrD2 at its native locus. However, a mutant protein
      unable to hydrolyze ATP or translocate along DNA was not able to compensate for
      lack of the wild-type protein. Therefore, we concluded that the essential role
      played by UvrD2 is unlikely to involve its DNA unwinding activity and is more
      likely to involve DNA translocation and, possibly, protein displacement.

PMID- 21725020
TI  - Genome sequence of Methyloversatilis universalis FAM5T, a methylotrophic
      representative of the order Rhodocyclales.
AB  - Rhodocyclales are representative of versatile bacteria that are able to utilize a
      wide variety of organic compounds for growth, but only a few strains have been
      isolated in pure culture thus far. Here we present the genome sequence of
      Methyloversatilis universalis FAM5(T), the first cultivable methylotrophic member
      of the order.

PMID- 21725021
TI  - Genome sequence of the Arctic methanotroph Methylobacter tundripaludum SV96.
AB  - Methylobacter tundripaludum SV96(T) (ATCC BAA-1195) is a psychrotolerant aerobic
      methane-oxidizing gammaproteobacterium (Methylococcales, Methylococcaceae) living
      in High Arctic wetland soil. The strain was isolated from soil harvested in July
      1996 close to the settlement Ny-Alesund, Svalbard, Norway (78 degrees 56'N, 11
      degrees 53'E), and described as a novel species in 2006. The genome includes pmo
      and pxm operons encoding copper membrane monooxygenases (Cu-MMOs), genes required
      for nitrogen fixation, and the nirS gene implicated in dissimilatory nitrite
      reduction to NO but no identifiable inventory for further processing of nitrogen
      oxides. These genome data provide the basis to investigate M. tundripaludum SV96,
      identified as a major player in the biogeochemistry of Arctic environments.

PMID- 21725022
TI  - Polycyclic aromatic hydrocarbon metabolic network in Mycobacterium vanbaalenii
      PYR-1.
AB  - This study investigated a metabolic network (MN) from Mycobacterium vanbaalenii
      PYR-1 for polycyclic aromatic hydrocarbons (PAHs) from the perspective of
      structure, behavior, and evolution, in which multilayer omics data are
      integrated. Initially, we utilized a high-throughput proteomic analysis to assess
      the protein expression response of M. vanbaalenii PYR-1 to seven different
      aromatic compounds. A total of 3,431 proteins (57.38% of the genome-predicted
      proteins) were identified, which included 160 proteins that seemed to be involved
      in the degradation of aromatic hydrocarbons. Based on the proteomic data and the
      previous metabolic, biochemical, physiological, and genomic information, we
      reconstructed an experiment-based system-level PAH-MN. The structure of PAH-MN,
      with 183 metabolic compounds and 224 chemical reactions, has a typical scale-free
      nature. The behavior and evolution of the PAH-MN reveals a hierarchical
      modularity with funnel effects in structure/function and intimate association
      with evolutionary modules of the functional modules, which are the ring cleavage
      process (RCP), side chain process (SCP), and central aromatic process (CAP). The
      189 commonly upregulated proteins in all aromatic hydrocarbon treatments provide
      insights into the global adaptation to facilitate the PAH metabolism. Taken
      together, the findings of our study provide the hierarchical viewpoint from
      genes/proteins/metabolites to the network via functional modules of the PAH-MN
      equipped with the engineering-driven approaches of modularization and
      rationalization, which may expand our understanding of the metabolic potential of
      M. vanbaalenii PYR-1 for bioremediation applications.

PMID- 21725023
TI  - Complete genome sequence of Amycolicicoccus subflavus DQS3-9A1T, an actinomycete
      isolated from crude oil-polluted soil.
AB  - Amycolicicoccus subflavus DQS3-9A1(T), isolated from crude oil-polluted soil in
      the Daqing Oilfield in China, is a type strain of a newly published novel species
      in the novel genus Amycolicicoccus. Here we report the complete genome of DQS3
      9A1(T)and genes associated with oil-polluted environment.

PMID- 21725024
TI  - Escherichia coli nucleoside diphosphate kinase mutants depend on translesion DNA
      synthesis to prevent mutagenesis.
AB  - Escherichia coli nucleoside diphosphate (NDP) kinase mutants have an increased
      frequency of spontaneous mutation, possibly due to uracil misincorporation into
      DNA. Here we show that NDP kinase mutants are dependent on translesion DNA
      synthesis, often a mutagenic form of DNA synthesis, to prevent mutagenesis.

PMID- 21725025
TI  - Complete genome sequences of Krokinobacter sp. strain 4H-3-7-5 and Lacinutrix sp.
      strain 5H-3-7-4, polysaccharide-degrading members of the family
      Flavobacteriaceae.
AB  - Two members of the family Flavobacteriaceae were isolated from subseafloor
      sediments using artificial seawater with cellulose, xylan, and chitin as the sole
      carbon and energy sources. Here, we present the complete genome sequences of
      Krokinobacter sp. strain 4H-3-7-5 and Lacinutrix sp. strain 5H-3-7-4, which both
      encode putatively novel enzymes involved in cellulose, hemicellulose, and chitin
      metabolism.

PMID- 21725027
TI  - Client-centered design of residential addiction and mental health care
      facilities: staff perceptions of their work environment.
AB  - In this article we discuss the findings from a series of focus groups conducted
      as part of a 3-year, mixed-method evaluation of clinical programs in a large
      mental health and substance use treatment facility in Canada. We examined the
      perceptions of clinical personnel on the physical design of new treatment units
      and the impact on service delivery and the work environment. The new physical
      design appeared to support client recovery and reduce stigma; however, it brought
      certain challenges. Participants reported a compromised ability to monitor
      clients, a lack of designated therapeutic spaces, and insufficient workspace for
      staff. They also thought that physical design positively facilitated
      communication and therapeutic relationships among clinicians and clients, and
      increased team cohesion. We suggest that, from these findings, new avenues for
      research on achieving the important balance between client and staff needs in
      health facility design can be explored.

PMID- 21725026
TI  - Adenosine and opioid receptors do not trigger the cardioprotective effect of mild
      hypothermia.
AB  - Mild hypothermia (32 degrees C-34 degrees C) exerts a potent cardioprotection in
      animal models of myocardial infarction. Recently, it has been proposed that this
      beneficial effect is related to survival signaling. We, therefore, hypothesized
      that the well-known cardioprotective pathways dependent on adenosine and/or
      opioid receptors could be the trigger of hypothermia-induced salvage. Open-chest
      rabbits were accordingly exposed to 30 minutes of coronary artery occlusion (CAO)
      under normothermic (NT) or hypothermic ([HT] 32 degrees C) conditions. In the
      latter, hypothermia was induced by total liquid ventilation with temperature
      controlled perfluorocarbons in order to effect ultrafast cooling and to
      accurately control cardiac temperature. After 4 hours of reperfusion, infarct and
      no-reflow zone sizes were assessed and quantified as a percentage of the risk
      zone. In animals experiencing HT ischemia, the infarct size was dramatically
      reduced as compared to NT animals (9% +/- 3% vs 55% +/- 2% of the risk zone,
      respectively). Importantly, administration of opioid and adenosine receptor
      antagonists (naloxone [6 mg/kg iv] and 8-(p-sulfophenyl) theophylline [20 mg/kg
      iv], respectively) did not alter the infarct size or affect the cardioprotective
      effect of hypothermia. Doses of these 2 antagonists were appropriately chosen
      since they blunted infarct size reduction induced by selective opioid or
      adenosine receptor stimulation with morphine (0.3 mg/kg iv) or N (6)
      cyclopentyladenosine ([CPA] 100 MUg/kg iv), respectively. Therefore, the
      cardioprotective effect of mild hypothermia is not triggered by either opioid or
      adenosine receptor activation, suggesting the involvement of other
      cardioprotective pathways.

PMID- 21725028
TI  - Functional impairment and occupational outcome in adults with ADHD.
AB  - OBJECTIVE: ADHD is associated with poor functional outcomes. The objectives were
      to investigate the prevalence of functional impairment and occupational status in
      a clinically referred sample of adults with ADHD and explore factors predicting
      occupational outcome. METHOD: A sample of 149 adults with a confirmed diagnosis
      of ADHD participated in the present study. Cross-sectional data were collected
      from the participant's medical records and from self-report questionnaires. A
      multiple regression model was applied to identify possible predictors of
      occupational outcome. RESULTS: Only 22.2% had ordinary work as their source of
      income, compared with 72% in the general population. The most prevalent comorbid
      disorders were lifetime depression (37.8%), substance abuse (28.1%), and alcohol
      abuse (23.3%). Age at first treatment with central stimulants and inattentiveness
      negatively predicted occupational outcome. CONCLUSION: Adult ADHD was associated
      with lower educational attainment and lower level of employment. Later age of
      first central stimulant treatment and higher inattentiveness ratings were
      associated with lower level of employment.

PMID- 21725029
TI  - OsWRKY45 alleles play different roles in abscisic acid signalling and salt stress
      tolerance but similar roles in drought and cold tolerance in rice.
AB  - Although allelic diversity of genes has been shown to contribute to many
      phenotypic variations associated with different physiological processes in
      plants, information on allelic diversity of abiotic stress-responsive genes is
      limited. Here it is shown that the alleles OsWRKY45-1 and OsWRKY45-2 play
      different roles in abscisic acid (ABA) signalling and salt stress adaptation in
      rice. The two alleles had different transcriptional responses to ABA and salt
      stresses. OsWRKY45-1-overexpressing lines showed reduced ABA sensitivity, whereas
      OsWRKY45-1-knockout lines showed increased ABA sensitivity. OsWRKY45-1 transgenic
      plants showed no obvious difference from negative controls in response to salt
      stress. In contrast, OsWRKY45-2-overexpressing lines showed increased ABA
      sensitivity and reduced salt stress tolerance, and OsWRKY45-2-suppressing lines
      showed reduced ABA sensitivity and increased salt stress tolerance. OsWRKY45-1
      and OsWRKY45-2 transgenic plants showed differential expression of a set of ABA-
      and abiotic stress-responsive genes, but they showed similar responses to cold
      and drought stresses. These results suggest that OsWRKY45-1 negatively and
      OsWRKY45-2 positively regulates ABA signalling and, in addition, OsWRKY45-2 but
      not OsWRKY45-1 negatively regulates rice response to salt stress. The different
      roles of the two alleles in ABA signalling and salt stress may be due to their
      transcriptional mediation of different signalling pathways.

PMID- 21725031
TI  - Reproductive competence from an annual and a perennial perspective.
AB  - Plants at early stages of development undergo a juvenile phase during which they
      are not competent to flower in response to environmental stimuli. The length of
      this phase varies among species and is extended in perennial plants particularly.
      In annuals, temporal changes in expression of microR156 (miR156), miR172, and
      their targets are correlated with the transition from the juvenile to the adult
      phase and flowering. This developmental transition in perennials is probably more
      complex than in other plants and the molecular mechanisms are less well
      understood. In addition, once perennials become adult and capable of reproduction
      they still keep some meristems in the vegetative state that contribute to their
      polycarpic growth habit. Juvenility and polycarpy, although considered as two
      different processes in perennials, might be related.

PMID- 21725030
TI  - QUASIMODO 3 (QUA3) is a putative homogalacturonan methyltransferase regulating
      cell wall biosynthesis in Arabidopsis suspension-cultured cells.
AB  - Pectins are complex polysaccharides that are essential components of the plant
      cell wall. In this study, a novel putative Arabidopsis S-adenosyl-L-methionine
      (SAM)-dependent methyltransferase, termed QUASIMODO 3 (QUA3, At4g00740), has been
      characterized and it was demonstrated that it is a Golgi-localized, type II
      integral membrane protein that functions in methylesterification of the pectin
      homogalacturonan (HG). Although transgenic Arabidopsis seedlings with
      overexpression, or knock-down, of QUA3 do not show altered phenotypes or changes
      in pectin methylation, this enzyme is highly expressed and abundant in
      Arabidopsis suspension-cultured cells. In contrast, in cells subjected to QUA3
      RNA interference (RNAi) knock-down there is less pectin methylation as well as
      altered composition and assembly of cell wall polysaccharides. Taken together,
      these observations point to a Golgi-localized QUA3 playing an essential role in
      controlling pectin methylation and cell wall biosynthesis in Arabidopsis
      suspension cell cultures.

PMID- 21725032
TI  - Expression profiles of differentially regulated genes during the early stages of
      apple flower infection with Erwinia amylovora.
AB  - To identify genes involved in the response to the fire blight pathogen Erwinia
      amylovora in apple (Malus*domestica), expression profiles were investigated using
      an apple oligo (70-mer) array representing 40, 000 genes. Blossoms of a fire
      blight-susceptible apple cultivar Gala were collected from trees growing in the
      orchard, placed on a tray in the laboratory, and spray-inoculated with a
      suspension of E. amylovora at a concentration of 10(8) cfu ml(-1). Uninoculated
      detached flowers served as controls at each time point. Expression profiles were
      captured at three different time points post-inoculation at 2, 8, and 24 h,
      together with those at 0 h (uninoculated). A total of about 3500 genes were found
      to be significantly modulated in response to at least one of the three time
      points. Among those, a total of 770, 855, and 1002 genes were up-regulated, by 2
      fold, at 2, 8, and 24 h following inoculation, respectively; while, 748, 1024,
      and 1455 genes were down-regulated, by 2-fold, at 2, 8, and 24 h following
      inoculation, respectively. Over the three time points post-inoculation, 365 genes
      were commonly up-regulated and 374 genes were commonly down-regulated. Both sets
      of genes were classified based on their functional categories. The majority of up
      regulated genes were involved in metabolism, signal transduction, signalling,
      transport, and stress response. A number of transcripts encoding proteins/enzymes
      known to be up-regulated under particular biotic and abiotic stress were also up
      regulated following E. amylovora treatment. Those up- or down-regulated genes
      encode transcription factors, signaling components, defense-related, transporter,
      and metabolism, all of which have been associated with disease responses in
      Arabidopsis and rice, suggesting similar response pathways are involved in apple
      blossoms.

PMID- 21725033
TI  - Cardiac magnetic resonance imaging of non-ischaemic cardiomyopathy.
AB  - Cardiomyopathy is defined as a heterogeneous group of diseases of the myocardium
      associated with mechanical and/or electrical dysfunction due to a variety of
      causes that are frequently genetic. These are either confined to the heart or are
      part of generalised systemic disorders, often leading to cardiovascular death or
      progressive heart failure related disability. Determination of exact aetiology of
      cardiomyopathy can be difficult but remains important for both treatment and
      prognosis. Cardiovascular magnetic resonance imaging allows comprehensive
      assessment of patients suspected to have cardiomyopathy and is therefore being
      increasingly used in diagnosis and follow-up of these patients. This review
      presents the main features of common cardiomyopathies on cardiovascular magnetic
      resonance imaging and highlights its role in providing additional information
      over and above the traditional diagnostic techniques.

PMID- 21725034
TI  - Recent advances in opioid prescription for chronic non-cancer pain.
AB  - Chronic pain is pain that persists past the normal time of healing, and is seen
      as a common problem with a significant socioeconomic impact. Pharmacological
      management for chronic non-cancer pain also involves the prescription of opioids,
      with the aim of an improved quality of life for the patient. New guidelines have
      been published to aid prescribing clinicians improve opioid safety and patient
      care, and include recommendations on when to refer patients to a pain specialist.
      In recent years there has been a rapid increase in opioid prescription in the UK
      and USA, prompting further concern regarding opioid abuse and side effects.
      Opioid use may also result in physical dependence and tolerance. Earlier
      recognition and diagnosis of unwanted effects of long-term opioid use is needed,
      such as opioid induced suppression of the hypothalamic-pituitary-gonadal axis,
      and opioid induced immunosuppression. Patients may themselves discontinue
      opioids, however, due to minor side effects. Recent advances in opioid
      prescription include the increasing use of transdermal preparations and extended
      release, oral, once daily preparations. New formulations of existing drugs have
      been developed, as well as a new chemical entity. Abuse deterrent formulations
      and delivery systems may prevent the artificial acceleration of drug delivery and
      reduce the potential for opioid addiction. Overdose concerns and the potential
      for fatal overdose may necessitate mandatory training for all clinicians who
      prescribe opioids. Despite the widespread use of opioids in the management of
      chronic non-cancer pain, significant research gaps remain. An improvement in the
      evidence base for its prescription is required.

PMID- 21725035
TI  - Encoding of smooth-pursuit eye movement initiation by a population of vermal
      Purkinje cells.
AB  - Lesion studies suggest that the oculomotor vermis (OMV) is critical for the
      initiation of smooth-pursuit eye movements (SPEMs); yet, its specific role has
      remained elusive. In this study, we tested the hypothesis that vermal Purkinje
      cells (PCs) may be needed to fine-tune the kinematic description of SPEM
      initiation. Recording from identified PCs from the monkey OMV, we observed that
      SPEM-related PCs were characterized by a formidable diversity of response
      profiles with typically only modest reflection of eye movement kinematics. In
      contrast, the PC population discharge could be perfectly predicted based on a
      linear combination of eye acceleration, velocity, and position. This finding is
      in full accord with a role of the OMV in shaping eye movement kinematics. It,
      moreover, supports the notion that this shaping action is based on a population
      code, whose anatomic basis is the convergence of PCs on target neurons in the
      cerebellar nuclei.

PMID- 21725036
TI  - Estradiol rapidly rescues synaptic transmission from corticosterone-induced
      suppression via synaptic/extranuclear steroid receptors in the hippocampus.
AB  - We investigated rapid protection effect by estradiol on corticosterone (CORT)
      induced suppression of synaptic transmission. Rapid suppression by 1 MUM CORT of
      long-term potentiation (LTP) at CA3-CA1 synapses was abolished via coperfusion of
      1 nM estradiol. N-methyl-D-aspartate (NMDA) receptor-derived field excitatory
      postsynaptic potential (NMDA-R-fEPSP) was used to analyze the mechanisms of these
      events. Estradiol abolished CORT-induced suppression of NMDA-R-fEPSP slope. This
      CORT-induced suppression was abolished by calcineurin inhibitor, and the rescue
      effect by estradiol on the CORT-induced suppression was inhibited by mitogen
      activated protein (MAP) kinase inhibitor. The CORT-induced suppressions of LTP
      and NMDA-R-fEPSP slope were abolished by glucocorticoid receptor (GR) antagonist,
      and the restorative effects by estradiol on these processes were mimicked by
      estrogen receptor alpha (ERalpha) and ERbeta agonists. Taken together, estradiol
      rapidly rescued LTP and NMDA-R-fEPSP slope from CORT-induced suppressions. A GR
      >calcineurin pathway is involved in these suppressive effects. The rescue effects
      by estradiol are driven via ERalpha or ERbeta->MAP kinase pathway.
      Synaptic/extranuclear GR, ERalpha, and ERbeta probably participate in these rapid
      events. Mass-spectrometric analysis determined that acute hippocampal slices used
      for electrophysiological measurements contained 0.48 nM estradiol less than
      exogenously applied 1 nM. In vivo physiological level of 8 nM estradiol could
      protect the intact hippocampus against acute stress-induced neural suppression.

PMID- 21725037
TI  - Distinctive neural processes during learning in autism.
AB  - This functional magnetic resonance imaging study compared the neural activation
      patterns of 18 high-functioning individuals with autism and 18 IQ-matched
      neurotypical control participants as they learned to perform a social judgment
      task. Participants learned to identify liars among pairs of computer-animated
      avatars uttering the same sentence but with different facial and vocal
      expressions, namely those that have previously been associated with lying versus
      truth-telling. Despite showing a behavioral learning effect similar to the
      control group, the autism group did not show the same pattern of decreased
      activation in cortical association areas as they learned the task. Furthermore,
      the autism group showed a significantly smaller increase in interregion
      synchronization of activation (functional connectivity) with learning than did
      the control group. Finally, the autism group had decreased structural
      connectivity as measured by corpus callosum size, and this measure was reliably
      related to functional connectivity measures. The findings suggest that cortical
      underconnectivity in autism may constrain the ability of the brain to rapidly
      adapt during learning.

PMID- 21725038
TI  - The modular neuroarchitecture of social judgments on faces.
AB  - Face-derived information on trustworthiness and attractiveness crucially
      influences social interaction. It is, however, unclear to what degree the
      functional neuroanatomy of these complex social judgments on faces reflects
      genuine social versus basic emotional and cognitive processing. To disentangle
      social from nonsocial contributions, we assessed commonalities and differences
      between the functional networks activated by judging social (trustworthiness,
      attractiveness), emotional (happiness), and cognitive (age) facial traits.
      Relative to happiness and age evaluations, both trustworthiness and
      attractiveness judgments selectively activated the dorsomedial prefrontal cortex
      and inferior frontal gyrus, forming a core social cognition network. Moreover,
      they also elicited a higher amygdalar response than even the emotional control
      condition. Both social judgments differed, however, in their top-down modulation
      of face-sensitive regions: trustworthiness judgments recruited the posterior
      superior temporal sulcus, whereas attractiveness judgments recruited the fusiform
      gyrus. Social and emotional judgments converged and, therefore, likely interact
      in the ventromedial prefrontal cortex. Social and age judgments, on the other
      hand, commonly engaged the anterior insula, inferior parietal cortex, and
      dorsolateral prefrontal cortex, which appear to subserve more cognitive aspects
      in social evaluation. These findings demonstrate the modularity of social
      judgments on human faces by separating the neural correlates of social, face
      specific, emotional, and cognitive processing facets.

PMID- 21725039
TI  - Comparison of clinical outcome of patients with non-small-cell lung cancer
      harbouring epidermal growth factor receptor exon 19 or exon 21 mutations.
AB  - AIMS: Deletion of exon 19 of the epidermal growth factor receptor (EGFR) and
      mutation of exon 21 are the most common EGFR mutations and predict higher
      response to EGFR tyrosine kinase inhibitors (TKI). Accumulating data show
      clinical differences in both response and survival between these two EGFR
      mutations. This study investigated the clinical impact of EGFR exon 19 deletion
      and L858R mutation by retrospectively analysing the clinical outcome of patients
      with advanced non-small-cell lung cancer (NSCLC) treated with EGFR TKI. METHODS:
      Patients harbouring EGFR exon 19 deletion or L858R mutations and who had received
      gefitinib or erlotinib treatment were identified. The response rate (RR),
      progression-free survival (PFS) and overall survival (OS) were determined for the
      two groups. EGFR mutation was determined by PCR-based direct sequencing. RESULTS:
      The study indentified 87 patients harbouring EGFR exon 19 deletion (n=61) or
      L858R mutation (n=26) who were treated with either gefitinib (n=83) or erlotinib
      (n=4). Patients with exon 19 deletion had significantly longer PFS, compared with
      patients with L858R mutation (9.3 vs 6.9 months, p=0.02). In a multivariate Cox
      regression model, EGFR exon 19 deletion was independently predictive of longer
      PFS (p=0.02). However, no significant differences in RR (64% vs 62%, p=0.83) and
      OS (17.7 vs 20.5 months, p=0.65) were observed between these two mutations.
      CONCLUSIONS: While no significant difference in OS was observed between EGFR exon
      19 deletion and L858R mutation, EGFR exon 19 deletion was predictive of longer
      PFS following EGFR TKI treatment in patients with advanced NSCLC.

PMID- 21725040
TI  - What is the significance of flat epithelial atypia and what are the management
      implications?
AB  - AIMS: To assess the significance of flat epithelial atypia (FEA) on core biopsy
      by evaluating the proportion of cases upgraded to in-situ and invasive carcinoma
      on further sampling with vacuum-assisted biopsy (VAB) or diagnostic surgical
      biopsy. METHODS: A retrospective analysis was performed of all core biopsies
      containing FEA and/or atypical intraductal proliferation (AIDP) in the pathology
      database from April 2008 to April 2010 (n=90). Before April 2009, the majority of
      core biopsies containing FEA and/or AIDP proceeded to surgical biopsy. From April
      2009 onwards, a new patient management pathway was introduced incorporating VAB
      to sample core biopsies containing FEA and/or AIDP as an alternative to surgical
      biopsy. RESULTS: Of 90 core biopsies, the following were identified: FEA only in
      42%; FEA with concomitant AIDP in 21% and AIDP only in 37%. There was a stepwise
      increase in the proportion of cases upgraded to in-situ or invasive carcinoma:
      19% in the FEA group; 29% in the FEA and AIDP group and 53% in the AIDP group. In
      the FEA-only group, one invasive tumour (grade 1 tubular carcinoma) and six cases
      of ductal carcinoma in situ were found. CONCLUSION: The presence of FEA on core
      biopsy warrants further tissue sampling to ensure concomitant malignancy is not
      missed. Sampling with VAB provides sufficient tissue for histopathological
      evaluation, reducing the need for surgical biopsy. It is important that the
      utilisation of VAB is incorporated into a safe patient management pathway with
      careful multidisciplinary team discussion to ensure radiological-pathological
      concordance.

PMID- 21725041
TI  - PAI-1 expression and its regulation by promoter 4G/5G polymorphism in clear cell
      renal cell carcinoma.
AB  - AIMS: To characterise patients with high plasminogen activator inhibitor-1 (PAI
      1) expression as oral PAI-1 antagonists are currently in preclinical trials, and
      to determine whether the PAI-1 promoter 4G/5G polymorphism regulates PAI-1
      expression in clear cell renal cell carcinoma (CCRCC). METHODS: PAI-1 expression
      was examined by immunohistochemistry in 69 CCRCC specimens. In addition, the
      promoter 4G/5G polymorphism was investigated by both allele-specific PCR and
      direct DNA sequencing. RESULTS: PAI-1 was overexpressed in 25/69 (36.2%) patients
      with CCRCC. PAI-1 staining was intense in tumour cells with a high Fuhrman
      nuclear grade and in spindle-shaped tumour cells. PAI-1 expression was
      significantly associated with older age at diagnosis (p=0.027), high nuclear
      grade (p<0.001), advanced clinical stage (p=0.030) and distant metastasis
      (p=0.009). In survival analyses, PAI-1 expression was correlated with disease
      free survival in Kaplan-Meier curves (p=0.015) but was not significant in the Cox
      hazards model (p=0.527). The frequencies of the promoter polymorphism were 24.6%
      (17/69) 4G/4G, 43.5% (30/69) 4G/5G and 31.9% (22/69) 5G/5G. The homozygous 4G/4G
      or 5G/5G group showed a tendency for a high nuclear grade (p=0.05) but the 4G/5G
      polymorphism was not related to other prognostic parameters. PAI-1 expression was
      poorly correlated with its promoter 4G/5G polymorphism (Spearman rho=0.088).
      CONCLUSIONS: CCRCC with high PAI-1 expression is characterised by older age, high
      nuclear grade, advanced stage, distant metastasis and/or shortened disease-free
      survival. PAI-1 expression is not affected by the promoter 4G/5G polymorphism.

PMID- 21725042
TI  - BCL-6 expression in mesenchymal tumours: an immunohistochemical and fluorescence
      in situ hybridisation study.
AB  - The BCL-6 proto-oncogene encodes a transcriptional repressor protein. Among
      normal tissues, BCL-6 expression is confined to germinal center B-cells and a
      subpopulation of T-helper cells. Little is known about BCL-6 expression in
      mesenchymal tissues. We examined a series of solitary fibrous tumor (SFT) and
      other mesenchymal tumors for BCL-6 expression. Immunohistochemistry for BCL-6 was
      performed on 64 mesenchymal tumors [26 SFT (19 benign/uncertain, 7 malignant), 6
      synovial sarcomas (SS), 5 gastrointestinal stromal tumors (GIST), 5 malignant
      peripheral nerve sheath tumors (MPNST), 5 leiomyosarcomas (LMS), 9 leiomyomas
      (LM) 4 desmoid tumors (DT), 4 perineuriomas (PN)]. Nuclear immunoreactivity was
      considered positive. Six BCL-6 positive SFT were also tested for BCL-6 gene
      rearrangement/amplification by FISH. Nuclear expression of BCL-6 was seen in
      13/26 SFT, 5/5 LMS, 1/9 LM, 5/6 SS, 1/5 GIST, 1/5 MPNST, 1/4 PN, and 0/5 DT. BCL
      6 expression was significantly more frequent in malignant (6/7) as compared with
      benign/uncertain SFT (6/19) (p=0.02) and in LMS (5/5) as compared with LM (1/9)
      (p=0.003). FISH for BCL-6 rearrangement/amplification was negative in all tested
      cases. We have observed BCL-6 expression in 50% or more of SFT, SS, and LMS, and
      in a lesser percentage of LM, GIST, MPNST and PN. Significantly more frequent
      expression of BCL-6 in malignant compared with benign/uncertain SFT and in LMS
      compared with LM suggests abnormalities in the BCL-6 signaling pathway may
      contribute to malignant transformation in at least some mesenchymal tumors. It is
      unlikely that BCL-6 expression in mesenchymal tumors is due to BCL-6 gene
      amplification or rearrangement.

PMID- 21725044
TI  - Equivalent continuous clearances EKR and stdK in incremental haemodialysis.
AB  - BACKGROUND: Many haemodialysis patients have residual renal function (RRF), which
      as such is insufficient to maintain satisfactory quality of life but reduces the
      demands of treatment and improves outcomes. In incremental dialysis, the dose is
      adjusted according to RRF, but how should it be done? METHODS: Urea generation
      rate (G) and distribution volume (V) were determined by the double-pool urea
      kinetic model in 225 haemodialysis sessions of 30 patients. The effect of
      different degrees of RRF on equivalent renal urea clearance (EKR), standard urea
      clearance (stdK) and urea concentrations and required treatment times to achieve
      the HEMO study standard dose equivalent EKR and stdK targets were studied by
      computer simulations. RESULTS: Ignoring RRF leads to underestimation of EKR,
      stdK, urea generation rate and protein equivalent of nitrogen appearance. Both
      EKR and stdK increase linearly with renal urea clearance (Kr). The HEMO standard
      dose equivalent EKRc is 13.8 mL/min/40 L and stdK/V 2.29 /wk (9.1 mL/min/40 L).
      The required treatment time to achieve the HEMO-equivalent targets has an almost
      linear inverse relationship to Kr. If the HEMO standard dose equivalent EKR or
      stdK is used as the target, RRF may replace several hours of weekly dialysis
      treatment time. stdK appreciates RRF more than EKR. CONCLUSIONS: RRF is included
      in the original EKR and stdK concepts. EKR and stdK--determined by kinetic
      modelling--are promising measures of adequacy in incremental dialysis.

PMID- 21725043
TI  - Reduced expression of desmocollin 2 is an independent prognostic biomarker for
      shorter patients survival in pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Cell--cell adhesion molecules such as desmosomes and cytokeratins may
      play a major role in epithelial--mesenchymal transition and have been suggested
      to have a relevant impact on tumour progression. This study investigated 15
      biomarkers in pancreatic ductal adenocarcinoma (PDAC) and correlated the results
      with clinicopathological parameters. METHODS: Tissue microarrays of 115 R0
      resected PDAC were constructed to evaluate the protein expression of 15 in genome
      wide expression profiling differentially expressed biomarkers. RESULTS: At the
      protein level a high expression of desmocollin 2 (DSC2) was observed in 90.4%,
      DSC1 (67.6%), DSC3 (0.9%), MDM2 (16.2%), CEA (64.8%), CK7 (85.2%), CK8 (96.5%),
      CK18 (96.5%), CK19 (93.9%), CK20 (11.5%), CA19-9 (86.6%), TLE1 (8.7%), PITX1
      (91.2%), factor H (95.7%) and mesothelin (9.6%). Reduced expression of DSC2 was
      statistically correlated with shorter patient survival, higher tumour grading and
      positive lymph node status (p=0.008, p=0.029, p=0.011, respectively). In
      multivariable analysis reduced expression of DSC2, higher tumour grading and
      positive lymph node status were independently correlated with shorter patient
      survival. CONCLUSIONS: Reduced expression of DSC2 is independently correlated
      with shorter patient survival, higher tumour grading and positive lymph node
      status in PDAC and could serve as a prognostic marker.

PMID- 21725046
TI  - Real-time automated paging and decision support for critical laboratory
      abnormalities.
AB  - BACKGROUND: For patients with critical laboratory abnormalities, timely clinical
      alerts with decision support could improve management and reduce adverse events.
      METHODS: The authors developed a real-time clinical alerting system for critical
      laboratory abnormalities. The system sent alerts to physicians as text messages
      to a smartphone or alphanumeric pager. Decision support was available via
      smartphone or hospital intranet. The authors evaluated the system in a
      prospective controlled stepped-wedge study with blinded outcome assessment in
      general internal medicine units at two academic hospitals. The outcomes were the
      proportion of potential clinical actions that were actually completed in response
      to the alert, and adverse events (worsening of condition or complications related
      to treatment of the condition). RESULTS: The authors evaluated 498 laboratory
      conditions on 271 patients. Overall, only 50% of potential clinical actions were
      carried out, and there were adverse clinical events within 48 h for 36% of the
      laboratory conditions. The median (IQR) proportion of potential clinical actions
      that were actually completed was 50% (33-75%) with alerting system on and 50% (33
      100%) with alerting system off (p=0.94, Wilcoxon rank sum test). When the
      alerting system was on (n=164 alerts) there were 67 adverse events within 48 h of
      the alerts (42%). When the alerting system was off (n=334 alerts), there were 112
      adverse events within 48 h (33%; difference: 9% higher with alerting system on,
      p=0.06). CONCLUSIONS: The provision of real-time clinical alerts and decision
      support for critical laboratory abnormalities did not improve clinical management
      or decrease adverse events.

PMID- 21725047
TI  - Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase
      deficient severe combined immune deficiency.
AB  - Genetic deficiency of adenosine deaminase (ADA) can cause profound lymphopenia
      and result in the clinical presentation of severe combined immune deficiency
      (SCID). However, because of the ubiquitous expression of ADA, ADA-deficient
      patients often present also with nonimmunologic clinical problems, affecting the
      skeletal, central nervous, endocrine, and gastrointestinal systems. We now report
      that myeloid dysplasia features and bone marrow hypocellularity are often found
      in patients with ADA-SCID. As a clinical correlate to this finding, we have
      observed vulnerability to antibiotic-induced myelotoxicity and prolonged
      neutropenia after nonmyeloablative chemotherapy. We have also noted that, in the
      absence of enzyme replacement therapy, absolute neutrophil counts of patients
      with ADA deficiency vary inversely with the accumulation of deoxynucleotides.
      These data have significant implications for the application of standard and
      investigational therapies to patients with ADA-SCID and support further studies
      to investigate the possibility that ADA deficiency is associated with a stem cell
      defect. These trials were registered at www.clinicaltrials.gov as #NCT00018018
      and #NCT00006319.

PMID- 21725048
TI  - SHP2 tyrosine phosphatase stimulates CEBPA gene expression to mediate cytokine
      dependent granulopoiesis.
AB  - G-CSF signals contribute to granulocyte lineage specification. We previously
      found that G-CSF induces SHP2 tyrosine phosphorylation and that chemical
      inhibition of SHP1/SHP2 reduces CFU-G and prevents G-CSF but not M-CSF activation
      of ERK. We now find that SHP2 shRNA knockdown in the 32Dcl3 granulocytic line
      reduces ERK activation, diminishes CEBPA protein and RNA expression and promoter
      histone acetylation, and inhibits granulopoiesis. Exogenous, shRNA-resistant SHP2
      rescues these effects of SHP2 knockdown, exogenous C/EBPalpha rescues
      granulocytic markers, and exogenous RUNX1 rescues C/EBPalpha. 32Dcl3 lines with
      knockdown of ERK1 and ERK2 retain normal levels of C/EBPalpha and differentiate
      normally in G-CSF despite also having reduced proliferation. SHP2 knockdown
      reduces CEBPA levels in lineage-negative murine marrow cells cultured in TPO,
      Flt3 ligand, and SCF, without affecting the rate of cell expansion. On transfer
      to IL-3, IL-6, and SCF to induce myelopoiesis, levels of granulocytic RNAs are
      reduced and monocyte-specific RNAs are increased by SHP2 knockdown, and there is
      a reduction in the percentage of CFU-G that form in methylcellulose and of
      granulocytes that develop in liquid culture. In summary, SHP2 is required for
      induction of C/EBPalpha expression and granulopoiesis in response to G-CSF or
      other cytokines independent of SHP2-mediated ERK activation.

PMID- 21725049
TI  - Down-regulation of the RUNX1-target gene NR4A3 contributes to hematopoiesis
      deregulation in familial platelet disorder/acute myelogenous leukemia.
AB  - RUNX1 encodes a DNA-binding alpha subunit of the core-binding factor, a
      heterodimeric transcription factor. RUNX1 is a master regulatory gene in
      hematopoiesis and its disruption is one of the most common aberrations in acute
      leukemia. Inactivating or dominant-negative mutations in the RUNX1 gene have been
      also identified in pedigrees of familial platelet disorders with a variable
      propensity to develop acute myeloid leukemia (FPD/AML). We performed analysis of
      hematopoiesis from 2 FPD/AML pedigrees with 2 distinct RUNX1 germline mutations,
      that is, the R139X in a pedigree without AML and the R174Q mutation in a pedigree
      with AML. Both mutations induced a marked increase in the clonogenic potential of
      immature CD34(+)CD38(-) progenitors, with some self-renewal capacities observed
      only for R174Q mutation. This increased proliferation correlated with reduction
      in the expression of NR4A3, a gene previously implicated in leukemia development.
      We demonstrated that NR4A3 was a direct target of RUNX1 and that restoration of
      NR4A3 expression partially reduced the clonogenic potential of patient
      progenitors. We propose that the down-regulation of NR4A3 in RUNX1-mutated
      hematopoietic progenitors leads to an increase in the pool of cells susceptible
      to be hit by secondary leukemic genetic events.

PMID- 21725050
TI  - Lenalidomide as initial therapy of elderly patients with chronic lymphocytic
      leukemia.
AB  - The best initial therapy for elderly patients with chronic lymphocytic leukemia
      (CLL) has not yet been defined. We investigated the activity of lenalidomide as
      initial therapy for elderly patients with CLL. Sixty patients with CLL 65 years
      of age and older received treatment with lenalidomide orally 5 mg daily for 56
      days, then titrated up to 25 mg/d as tolerated. Treatment was continued until
      disease progression. At a median follow-up of 29 months, 53 patients (88%) are
      alive and 32 patients (53%) remain on therapy. Estimated 2-year progression-free
      survival is 60%. The overall response rate to lenalidomide therapy is 65%,
      including 10% complete response, 5% complete response with residual cytopenia, 7%
      nodular partial response, and 43% partial response. Neutropenia is the most
      common grade 3 or 4 treatment-related toxicity observed in 34% of treatment
      cycles. Major infections or neutropenic fever occurred in 13% of patients.
      Compared with baseline levels, we noted an increase in serum immunoglobulin
      levels across all classes, and a reduction in CCL3 and CCL4 plasma levels was
      noted in responding patients. Lenalidomide therapy was well tolerated and induced
      durable remissions in this population of elderly, symptomatic patients with CLL.
      This study was registered at www.clinicaltrials.gov as #NCT00535873.

PMID- 21725051
TI  - Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and
      self-reactive antibodies with similar reactivity.
AB  - One-third of all splenic marginal zone lymphomas (SMZL) use the IgH VH1-02 gene.
      These cases are usually not associated with hepatitis C virus infection. Of
      interest, the rearranged VH1-02 genes display similar complementarity determining
      regions 3, a finding confirmed by our study. The latter suggests that these SMZL
      may produce antibodies with similar reactivity. We produced recombinant
      antibodies from 5 SMZL cases with VH1-02 gene rearrangement to study the binding
      reactivity of these antibodies. Surprisingly, the recombinant antibodies
      demonstrated poly- and self-reactivity as demonstrated by their reactivity with
      nuclear, cytoplasmic, as well as membranous antigens expressed by human cells and
      by reactivity with human serum. This polyreactivity was specific as demonstrated
      by ELISA. The antibodies did not react with proteins on the cell surface that are
      induced by apoptosis as shown for antibodies produced by chronic lymphatic
      leukemia with VH1-02 gene rearrangement. The results indicate that a common
      subset of SMZL arises from polyreactive B cells, a subset of marginal zone B
      cells that are important in the immunologic defense against infection.

PMID- 21725052
TI  - Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase
      1/2 study in patients with myelofibrosis.
AB  - In addition to dysregulated JAK/STAT signaling, activation of the AKT/mTOR
      pathway occurs in myelofibrosis, a myeloproliferative neoplasm with no approved
      therapies. We conducted a phase 1/2 study with everolimus, an mTOR inhibitor, in
      39 high- or intermediate-risk primary or postpolycythemia vera/postessential
      thrombocythemia myelofibrosis subjects. Responses were evaluated in 30 patients
      of phase 2. No dose-limiting toxicity was observed in phase 1 up to 10 mg/d. When
      this dose was used in phase 2, grade >= 3 toxicities were infrequent; the
      commonest toxicity was grade 1-2 stomatitis. Rapid and sustained splenomegaly
      reduction of > 50% and > 30% occurred in 20% and 44% of subjects, respectively. A
      total of 69% and 80% experienced complete resolution of systemic symptoms and
      pruritus. Response in leukocytosis, anemia, and thrombocytosis occurred in 15%
      25%. Clinical responses were not associated with reduced JAK2V617F burden,
      circulating CD34(+) cells, or cytokine levels, whereas CCDN1 mRNA and phospho
      p70S6K level, known targets of mTOR, and WT1 mRNA were identified as possible
      biomarkers associated with response. Response rate was 60% when European Network
      for Myelofibrosis criteria were used (8 major, 7 moderate, 3 minor responses) or
      23% when IWG-MRT criteria (1 partial response, 6 clinical improvements) were
      used. These results provide proof-of-concept that targeting mTOR pathway in
      myelofibrosis may be clinically relevant.

PMID- 21725053
TI  - Prospective evaluation of a pharmacogenetics-guided warfarin loading and
      maintenance dose regimen for initiation of therapy.
AB  - Single-nucleotide polymorphisms in genes that affect warfarin metabolism
      (cytochrome P450 2C9 gene, CYP2C9) and response (vitamin K epoxide reductase
      complex 1 gene, VKORC1) have an important influence on warfarin therapy,
      particularly during initiation; however, there is a lack of consensus regarding
      the optimal pharmacogenetics-based initiation strategy. We conducted a
      prospective cohort study in which patients requiring warfarin therapy for atrial
      fibrillation or venous thromboembolism were initiated with a novel
      pharmacogenetics-initiation protocol (WRAPID, Warfarin Regimen using A
      Pharmacogenetics-guided Initiation Dosing) that incorporated loading and
      maintenance doses based on genetics, clinical variables, and response (n = 167,
      followed up for 90 days), to assess the influence of genetic variations on
      anticoagulation responses. Application of the WRAPID algorithm resulted in a
      negligible influence of genetic variation in VKORC1 or CYP2C9 on time to
      achievement of first therapeutic response (P = .52, P = .28) and risk of
      overanticoagulation (P = .64, P = .96). After adjustment for covariates, time to
      stable anticoagulation was not influenced by VKORC1 or CYP2C9 genotype.
      Importantly, time spent within or above the therapeutic range did not differ
      among VKORC1 and CYP2C9 genotype groups. Moreover, the overall time course of the
      anticoagulation response among the genotype groups was similar and predictable.
      We demonstrate the clinical utility of genetics-guided warfarin initiation with
      the WRAPID protocol to provide safe and optimal anticoagulation therapy for
      patients with atrial fibrillation or venous thromboembolism.

PMID- 21725055
TI  - Chronic IFN-gamma production in mice induces anemia by reducing erythrocyte life
      span and inhibiting erythropoiesis through an IRF-1/PU.1 axis.
AB  - Anemia of chronic disease is a complication accompanying many inflammatory
      diseases. The proinflammatory cytokine IFN-gamma has been implicated in this form
      of anemia, but the underlying mechanism remains unclear. Here we describe a novel
      mouse model for anemia of chronic disease, in which enhanced CD27-mediated
      costimulation strongly increases the formation of IFN-gamma-producing effector T
      cells, leading to a progressive anemia. We demonstrate that the anemia in these
      mice is fully dependent on IFN-gamma and that this cytokine reduces both the life
      span and the formation of red blood cells. Molecular analysis revealed that IFN
      gamma induces expression of the transcription factors of interferon regulatory
      factor-1 (IRF-1) and PU.1 in both murine and human erythroid precursors. We found
      that, on IFN-gamma stimulation, IRF-1 binds to the promoter of SPI.1 (PU.1) and
      induces PU.1 expression, leading to inhibition of erythropoiesis. Notably, down
      regulation of either IRF-1 or PU.1 expression is sufficient to overcome IFN-gamma
      induced inhibition of erythropoiesis. These findings reveal a molecular mechanism
      by which chronic exposure to IFN-gamma induces anemia.

PMID- 21725054
TI  - MicroRNA function in myeloid biology.
AB  - The past 5 years have seen an explosion of knowledge about miRNAs and their roles
      in hematopoiesis, cancer, and other diseases. In myeloid development, there is a
      growing appreciation for both the importance of particular miRNAs and the unique
      features of myelopoiesis that are being uncovered by experimental manipulation of
      miRNAs. Here, we review in detail the roles played by 4 miRNAs, miR-125, miR-146,
      miR-155, and miR-223 in myeloid development and activation, and correlate these
      roles with their dysregulation in disease. All 4 miRNAs demonstrate effects on
      myelopoiesis, and their loss of function or overexpression leads to pathologic
      phenotypes in the myeloid lineage. We review their functions at distinct points
      in development, their targets, and the regulatory networks that they are embedded
      into in the myeloid lineage.

PMID- 21725058
TI  - Inhaled nitric oxide and bronchopulmonary dysplasia.

PMID- 21725056
TI  - Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib
      (R115777) in patients with relapsed and refractory lymphomas.
AB  - A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was
      conducted in 93 adult patients with relapsed or refractory lymphoma. Patients
      received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The
      median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell,
      indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response
      rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19
      responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL,
      1 follicular grade 2, and 4 HL. The median response duration for the 19
      responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in
      the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4
      toxicities observed were fatigue and reversible myelosuppression. Correlative
      studies suggest that Bim and Bcl-2 should be examined as potential predictors of
      response in future studies. These results indicate that tipifarnib has activity
      in lymphoma, particularly in heavily pretreated HL/T types, with little activity
      in follicular NHL. In view of its excellent toxicity profile and novel mechanism
      of action, further studies in combination with other agents appear warranted.
      This trial is registered at www.clinicaltrials.gov as #NCT00082888.

PMID- 21725060
TI  - Visualization and biochemical analyses of the emerging mammalian 14-3-3
      phosphoproteome.
AB  - Hundreds of candidate 14-3-3-binding (phospho)proteins have been reported in
      publications that describe one interaction at a time, as well as high-throughput
      14-3-3-affinity and mass spectrometry-based studies. Here, we transcribed these
      data into a common format, deposited the collated data from low-throughput
      studies in MINT (http://mint.bio.uniroma2.it/mint), and compared the low- and
      high-throughput data in VisANT graphs that are easy to analyze and extend.
      Exploring the graphs prompted questions about technical and biological
      specificity, which were addressed experimentally, resulting in identification of
      phosphorylated 14-3-3-binding sites in the mitochondrial import sequence of the
      iron-sulfur cluster assembly enzyme (ISCU), cytoplasmic domains of the
      mitochondrial fission factor (MFF), and endoplasmic reticulum-tethered receptor
      expression-enhancing protein 4 (REEP4), RNA regulator SMAUG2, and cytoskeletal
      regulatory proteins, namely debrin-like protein (DBNL) and kinesin light chain
      (KLC) isoforms. Therefore, 14-3-3s undergo physiological interactions with
      proteins that are destined for diverse subcellular locations. Graphing and
      validating interactions underpins efforts to use 14-3-3-phosphoproteomics to
      identify mechanisms and biomarkers for signaling pathways in health and disease.

PMID- 21725062
TI  - Retraction. Ouyang,Y, Xu Y, Petrini M, Zhang Q, Chen Y. (2011). Breastfeeding
      knowledge, attitudes, and behavior of female Chinese physicians in 2009. J Hum
      Lact.

PMID- 21725061
TI  - CIN85 interacting proteins in B cells-specific role for SHIP-1.
AB  - The Cbl-interacting 85-kDa protein (CIN85) plays an important role as a negative
      regulator of signaling pathways induced by receptor tyrosine kinases. By
      assembling multiprotein complexes this versatile adaptor enhances receptor
      tyrosine kinase-activated clathrin-mediated endocytosis and reduces
      phosphatidylinositol-3-kinase-induced phosphatidylinositol-3,4,5-trisphosphate
      production. Here we report the expression of CIN85 in primary splenic B
      lymphocytes and the B-lymphoma cell lines WEHI 231 and Ba/F3. Cross-linking of
      the B cell antigen receptor resulted in an increased association of CIN85 with
      the ubiquitin ligase Cbl. Through a systematic pull-down proteomics approach we
      identified 51 proteins that interact with CIN85 in B cells, including proteins
      not shown previously to be CIN85-associated. Among these proteins, the SH2
      containing inositol phosphatase 1 (SHIP-1) co-precipitated with both the full
      length CIN85 and each of its three SH3 domains. We also showed that this
      association is constitutive and depends on a region of 79 amino acids near the
      carboxyl terminus of SHIP-1, a region rich in potential SH3 domain binding sites.
      Because SHIP-1 is a major negative regulator of the phosphatidylinositol-3-kinase
      pathway in lymphocytes, we hypothesize that the interaction between SHIP-1 and
      CIN85 might synergistically facilitate the down-regulation of
      phosphatidylinositol-3,4,5-trisphosphate levels.

PMID- 21725063
TI  - Reduction in tonal discriminations predicts receptive emotion processing deficits
      in schizophrenia and schizoaffective disorder.
AB  - INTRODUCTION: Schizophrenia patients show decreased ability to identify emotion
      based upon tone of voice (voice emotion recognition), along with deficits in
      basic auditory processing. Interrelationship among these measures is poorly
      understood. METHODS: Forty-one patients with schizophrenia/schizoaffective
      disorder and 41 controls were asked to identify the emotional valence (happy,
      sad, angry, fear, or neutral) of 38 synthesized frequency-modulated (FM) tones
      designed to mimic key acoustic features of human vocal expressions. The mean
      (F0M) and variability (F0SD) of fundamental frequency (pitch) and absence or
      presence of high frequency energy (HF500) of the tones were independently
      manipulated to assess contributions on emotion identification. Forty patients and
      39 controls also completed tone-matching and voice emotion recognition tasks.
      RESULTS: Both groups showed a nonrandom response pattern (P < .0001). Stimuli
      with highest and lowest F0M/F0SD were preferentially identified as happy and sad,
      respectively. Stimuli with low F0M and midrange F0SD values were identified as
      angry. Addition of HF500 increased rates of angry and decreased rates of sad
      identifications. Patients showed less differentiation of response across
      frequency changes, leading to a highly significant between-group difference in
      response pattern to maximally identifiable stimuli (d = 1.4). The differential
      identification pattern for FM tones correlated with deficits in basic tone
      matching ability (P = .01), voice emotion recognition (P < .001), and negative
      symptoms (P < .001). CONCLUSIONS: Specific FM tones conveyed reliable emotional
      percepts in both patients and controls and correlated highly with deficits in
      ability to recognize information based upon tone of voice, suggesting significant
      bottom-up contributions to social cognition and negative symptom impairments in
      schizophrenia.

PMID- 21725064
TI  - Molecular phylogeny of the subgenus Ceratotropis (genus Vigna, Leguminosae)
      reveals three eco-geographical groups and Late Pliocene-Pleistocene
      diversification: evidence from four plastid DNA region sequences.
AB  - BACKGROUND AND AIMS: The subgenus Ceratotropis in the genus Vigna is widely
      distributed from the Himalayan highlands to South, Southeast and East Asia.
      However, the interspecific and geographical relationships of its members are
      poorly understood. This study investigates the phylogeny and biogeography of the
      subgenus Ceratotropis using chloroplast DNA sequence data. METHODS: Sequence data
      from four intergenic spacer regions (petA-psbJ, psbD-trnT, trnT-trnE and trnT
      trnL) of chloroplast DNA, alone and in combination, were analysed using Bayesian
      and parsimony methods. Divergence times for major clades were estimated with
      penalized likelihood. Character evolution was examined by means of parsimony
      optimization and MacClade. KEY RESULTS: Parsimony and Bayesian phylogenetic
      analyses on the combined data demonstrated well-resolved species relationships in
      which 18 Vigna species were divided into two major geographical clades: the East
      Asia-Southeast Asian clade and the Indian subcontinent clade. Within these two
      clades, three well-supported eco-geographical groups, temperate and subtropical
      (the East Asia-Southeast Asian clade) and tropical (the Indian subcontinent
      clade), are recognized. The temperate group consists of V. minima, V. nepalensis
      and V. angularis. The subtropical group comprises the V. nakashimae-V.
      riukiuensis-V. minima subgroup and the V. hirtella-V. exilis-V. umbellata
      subgroup. The tropical group contains two subgroups: the V. trinervia-V. reflexo
      pilosa-V. trilobata subgroup and the V. mungo-V. grandiflora subgroup. An
      evolutionary rate analysis estimated the divergence time between the East Asia
      Southeast Asia clade and the Indian subcontinent clade as 3.62 +/- 0.3 million
      years, and that between the temperate and subtropical groups as 2.0 +/- 0.2
      million years. CONCLUSIONS: The findings provide an improved understanding of the
      interspecific relationships, and ecological and geographical phylogenetic
      structure of the subgenus Ceratotropis. The quaternary diversification of the
      subgenus Ceratotropis implicates its geographical dispersal in the south-eastern
      part of Asia involving adaptation to climatic condition after the collision of
      the Indian subcontinent with the Asian plate. The phylogenetic results indicate
      that the epigeal germination is plesiomorphic, and the germination type evolved
      independently multiple times in this subgenus, implying its limited taxonomic
      utility.

PMID- 21725065
TI  - Mechanistic computational model of steroidogenesis in H295R cells: role of
      oxysterols and cell proliferation to improve predictability of biochemical
      response to endocrine active chemical--metyrapone.
AB  - The human adrenocortical carcinoma cell line H295R is being used as an in vitro
      steroidogenesis screening assay to assess the impact of endocrine active
      chemicals (EACs) capable of altering steroid biosynthesis. To enhance the
      interpretation and quantitative application of measurement data in risk
      assessments, we are developing a mechanistic computational model of adrenal
      steroidogenesis in H295R cells to predict the synthesis of steroids from
      cholesterol (CHOL) and their biochemical response to EACs. We previously
      developed a deterministic model that describes the biosynthetic pathways for the
      conversion of CHOL to steroids and the kinetics for enzyme inhibition by the EAC,
      metyrapone (MET). In this study, we extended our dynamic model by (1) including a
      cell proliferation model supported by additional experiments and (2) adding a
      pathway for the biosynthesis of oxysterols (OXY), which are endogenous products
      of CHOL not linked to steroidogenesis. The cell proliferation model predictions
      closely matched the time-course measurements of the number of viable H295R cells.
      The extended steroidogenesis model estimates closely correspond to the measured
      time-course concentrations of CHOL and 14 adrenal steroids both in the cells and
      in the medium and the calculated time-course concentrations of OXY from control
      and MET-exposed cells. Our study demonstrates the improvement of the extended,
      more biologically realistic model to predict CHOL and steroid concentrations in
      H295R cells and medium and their dynamic biochemical response to the EAC, MET.
      This mechanistic modeling capability could help define mechanisms of action for
      poorly characterized chemicals for predictive risk assessments.

PMID- 21725066
TI  - Neuron-specific impairment of inter-chromosomal pairing and transcription in a
      novel model of human 15q-duplication syndrome.
AB  - Although the etiology of autism remains largely unknown, cytogenetic and genetic
      studies have implicated maternal copy number gains of 15q11-q13 in 1-3% of autism
      cases. In order to understand how maternal 15q duplication leads to dysregulation
      of gene expression and altered chromatin interactions, we used microcell-mediated
      chromosome transfer to generate a novel maternal 15q duplication model in a human
      neuronal cell line. Our 15q duplication neuronal model revealed that by
      quantitative RT-PCR, transcript levels of NDN, SNRPN, GABRB3 and CHRNA7 were
      reduced compared with expected levels despite having no detectable alteration in
      promoter DNA methylation. Since 15q11-q13 alleles have been previously shown to
      exhibit homologous pairing in mature human neurons, we assessed homologous
      pairing of 15q11-q13 by fluorescence in situ hybridization. Homologous pairing of
      15q11-q13 was significantly disrupted by 15q duplication. To further understand
      the extent and mechanism of 15q11-q13 homologous pairing, we mapped the minimal
      region of homologous pairing to a ~500 kb region at the 3' end of GABRB3 which
      contains multiple binding sites for chromatin regulators MeCP2 and CTCF. Both
      active transcription and the chromatin factors MeCP2 and CTCF are required for
      the homologous pairing of 15q11-q13 during neuronal maturational differentiation.
      These data support a model where 15q11-q13 genes are regulated epigenetically at
      the level of both inter- and intra-chromosomal associations and that chromosome
      imbalance disrupts the epigenetic regulation of genes in 15q11-q13.

PMID- 21725067
TI  - Perturbation of U2AF65/NXF1-mediated RNA nuclear export enhances RNA toxicity in
      polyQ diseases.
AB  - Expanded CAG RNA has recently been reported to contribute to neurotoxicity in
      polyglutamine (polyQ) degeneration. In this study, we showed that RNA carrying an
      expanded CAG repeat progressively accumulated in the cell nucleus of transgenic
      Drosophila that displayed degeneration. Our gene knockdown and mutant analyses
      demonstrated that reduction of U2AF50 function, a gene involved in RNA nuclear
      export, intensified nuclear accumulation of expanded CAG RNA and resulted in a
      concomitant exacerbation of expanded CAG RNA-mediated toxicity in vivo. We found
      that the human U2AF50 ortholog, U2AF65, interacted directly and specifically with
      expanded CAG RNA via its RRM3 domain. We further identified an RNA/protein
      complex that consisted of expanded CAG RNA, U2AF65 and the NXF1 nuclear export
      receptor. The U2AF65 protein served as an adaptor to link expanded CAG RNA to
      NXF1 for RNA export. Finally, we confirmed the nuclear accumulation of expanded
      CAG RNA in symptomatic polyQ transgenic mice and also observed a
      neurodevelopmental downregulation of U2AF65 protein levels in mice. Altogether,
      our findings demonstrate that the cell nucleus is a site where expanded CAG RNA
      exerts its toxicity. We also provide a novel mechanistic explanation to how
      perturbation of RNA nuclear export would contribute to polyQ degeneration.

PMID- 21725068
TI  - Noise exposure and serious injury to active sawmill workers in British Columbia.
AB  - BACKGROUND: Occupational noise might increase the risk of workplace injury
      through a variety of mechanisms, including interference with communication and
      increased stress. OBJECTIVES: The purpose of this study was to assess the effect
      of chronic noise exposure on serious workplace injury, and how the timing of
      exposure influenced risk. METHODS: The authors examined a cohort of 26 000
      workers, who worked between 1950 and 1989. Cases were those hospitalised for a
      work-related injury (ICD-9 codes 800-999, and E codes E800-E999), from April 1989
      to December 1998. Cumulative exposure levels were estimated for subjects based on
      a quantitative retrospective exposure assessment. An internal comparison of
      cumulative noise exposure and subchronic durations of noise exposure and injury
      was conducted using Poisson regression. There were 163 cases for the cumulative
      and 161 cases for the subchronic analysis. RESULTS: Cumulative noise exposure
      were associated with a decreased risk for injuries, with the risk generally
      decreasing as cumulative noise levels increased, while most durations of
      subchronic exposure were associated with an increased risk for injury. An inverse
      U-shaped trend was observed with the time period of 90 days to 1 year
      demonstrating the most elevated RR compared with 0-1 days of exposure.
      CONCLUSIONS: Workers highly exposed to noise, or exposed for long periods of
      time, might develop effective methods of communicating the risk and preventing
      injuries when exposed to noise.

PMID- 21725069
TI  - Characteristics of 3687 pneumoconiosis cases between 1985 and 2006 in Xinjiang
      Uyghur's Autonomous Region, China.

PMID- 21725070
TI  - Occupational noise exposure assessment using O*NET and its application to a study
      of hearing loss in the US general population.
AB  - OBJECTIVES: Although occupational noise is a well known risk factor for hearing
      loss, little epidemiological evidence has been reported on its association with
      hearing loss in the general population, in part, because of the difficulty in
      exposure assessment. This study introduced a quantitative occupational noise
      exposure assessment tool using the Occupational Information Network (O*NET)
      database and evaluated its applicability for epidemiological research using data
      from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.
      METHODS: The O*NET noise exposure data were assessed by questionnaires across
      numerous occupations, asking the frequency of exposure to sounds and noise levels
      that are distracting and uncomfortable (with five possible responses from 'never'
      to 'every day'). Means of the O*NET noise scores were computed to correspond to
      NHANES occupational categories and assigned to 3828 adults aged 20-69 years, who
      participated in the 1999-2004 NHANES. Pure-tone averages (PTA) of hearing
      thresholds at 0.5, 1, 2 and 4 kHz were computed, and hearing loss was defined as
      a PTA >25 dB in either ear. Linear and logistic regression models with either
      continuous or quintiles of the O*NET noise scores were fitted on log-transformed
      PTA and binary hearing loss, respectively. RESULTS: Noise scores ranged from 1.80
      to 4.37 with mean+/-SE of 3.06+/-0.02. After controlling for potential
      confounders, the highest (vs lowest) noise score quintile had a 22.5% (95% CI
      11.0% to 35.2%) increase in PTA, and there was a linear dose-dependent trend
      across the quintiles of noise scores (p trend<0.0001). The adjusted OR for
      hearing loss comparing the highest with the lowest noise score quintiles was 2.1
      (95% CI 1.2 to 3.6). CONCLUSION: This study suggests that the O*NET noise score
      is a useful tool for examining occupational noise-induced health effects in the
      general population in the absence of actual occupational noise exposure
      assessment data.

PMID- 21725071
TI  - Air exposure assessment of TDI and biological monitoring of TDA in urine in
      workers in polyurethane foam industry.
AB  - OBJECTIVES: Toluene diisocyanate (TDI) is used in the manufacturing process of
      polyurethane (PU) foams and is a potent inducer of occupational asthma. The
      objective of this study was to evaluate the correlation between the exposure to
      total TDI (2,4- and 2,6-TDI) in air and the corresponding biomarker concentration
      of total TDA (2,4- and 2,6-TDA) in hydrolysed urine. The aim was also to propose
      an appropriate biological exposure limit for total TDA in urine. METHODS: 9
      workers from two production lines in a PU foam producing plant were studied.
      Personal exposure to TDI during four representative production shifts was
      monitored by an active air sampling method (filter impregnated with 1-(2
      methoxyphenyl)piperazine) and quantified by high-performance liquid
      chromatography and diode array detection (NIOSH n degrees  2535, 5521). In
      parallel, pre-shift and post-shift urinary samples were collected from the
      exposed workers, and TDA concentrations were determined by gas chromatography
      mass spectrometry after alkaline hydrolysis. All samples were collected on four
      measuring days: two Fridays (end of workweek) and two Mondays (start of workweek)
      separated by a weekend without exposure. RESULTS: Strong correlations between the
      personal air concentrations of total TDI and the corresponding biomarker levels
      of total TDA in urine (r=0.816) were observed. An increase of 18.12 MUg TDA/l
      (post-shift minus pre-shift concentration) corresponds to an exposure of 5 ppb
      (37 MUg/m(3), the current American Conference of Governmental Industrial
      Hygienists threshold limit value) during the shift. CONCLUSIONS: The increase in
      TDA during the shift is a suitable biomarker for exposure to TDI during the same
      shift. Further research is needed to evaluate the use of start of week or end of
      week post-shift TDA in urine as biomarker since TDA was found to accumulate
      during the working week and thus the moment of sampling will clearly influence
      the result.

PMID- 21725072
TI  - Assessment of long-term and recent pesticide exposure among rural school children
      in Nicaragua.
AB  - OBJECTIVE: This study assessed pesticide exposure of children in rural Nicaragua
      in relation to parental pesticide use, from around conception to current school
      age, as part of an epidemiological evaluation of neurodevelopment effects.
      METHODS: We included 132 children whose parents were subsistence farmers or
      plantation workers, or had an agricultural history. As proxies for children's
      long-term exposures, we constructed cumulative parental pesticide-specific use
      indices for periods before and after the child's birth from data obtained using
      an icon-calendar-based questionnaire, of application hours (h) for plantation
      workers and subsistence farmers, and of kilograms of active ingredients (ai) only
      for subsistence farmers. Pesticide residues of TCPY, 3-PBA and 2,4-D were
      analysed in children's urine as indicators for current exposures. RESULTS: Life
      time indices were highest for the organophosphates chlorpyrifos (median 114 h
      (min 2; max 1584), 19.2 kg ai (min 0.37; max 548)) and methamidophos (84 h (6;
      1964), 12.2 kg ai (0.30; 780)). The P50 values of children's urinary residues
      were 3.7 MUg/g creatinine for TCPY, 2.8 for 3-PBA and 0.9 for 2,4-D; TCPY values
      are comparable with those in other countries, but 3-PBA and 2,4-D are
      considerably higher. The maximum levels for all three pesticides are the highest
      reported for children. Residues increased on days after application, but most
      high residue levels were unrelated to parental pesticide applications.
      CONCLUSION: Urinary pesticide residues reveal high environmental exposure among
      children in rural Nicaragua. The quantitative parental pesticide use indices as
      proxies for children's exposures during different periods may be useful for the
      evaluation of developmental health effects.

PMID- 21725073
TI  - Glycomic analysis of human mast cells, eosinophils and basophils.
AB  - In allergic diseases such as asthma, eosinophils, basophils and mast cells,
      through release of preformed and newly generated mediators, granule proteins and
      cytokines, are recognized as key effector cells. While their surface protein
      phenotypes, mediator release profiles, ontogeny, cell trafficking and genomes
      have been generally explored and compared, there has yet to be any thorough
      analysis and comparison of their glycomes. Such studies are critical to
      understand the contribution of carbohydrates to the induction and regulation of
      allergic inflammatory responses and are now possible using improved technologies
      for detecting and characterizing cell-derived glycans. We thus report here the
      application of high-sensitivity mass spectrometric-based glycomics methodologies
      to the analysis of N-linked glycans derived from isolated populations of human
      mast cells, eosinophils and basophils. The samples were subjected to matrix
      assisted laser desorption ionization (MALDI) time-of-flight (TOF) screening
      analyses and MALDI-TOF/TOF sequencing studies. Results reveal substantive
      quantities of terminal N-acetylglucosamine containing structures in both the
      eosinophil and the basophil samples, whereas mast cells display greater relative
      quantities of sialylated terminal epitopes. For the first time, we characterize
      the cell surface glycan structures of principal allergic effector cells, which by
      interaction with glycan-binding proteins (e.g. lectins) have the possibility to
      dictate cellular functions, and might thus have important implications for the
      pathogenesis of inflammatory and allergic diseases.

PMID- 21725075
TI  - Anxiety and depression in polycystic ovary syndrome: a systematic review and meta
      analysis.
AB  - BACKGROUND: Our aim was to assess differences in anxiety and depression between
      women with and without (controls) polycystic ovary syndrome (PCOS). METHODS: We
      conducted a systematic review and meta-analysis of published literature comparing
      women with PCOS to control groups on anxiety and depression. Electronic databases
      were searched up to 17 December 2010. The inverse variance method based, as
      appropriate, on a random- or fixed-effects model in Review Manager, Version 5 was
      used to analyse the data. RESULTS: Twelve comparative studies were included; all
      studies assessed depression (910 women with PCOS and 1347 controls) and six also
      assessed anxiety (208 women with PCOS and 169 controls). Analysis revealed higher
      depression (Z = 17.92, P < 0.00001; Hedges' g = 0.82; 95% CI 0.73-0.92) and
      anxiety (Z = 5.03, P < 0.00001; Hedges' g = 0.54; 95% CI 0.33-0.75) scores in the
      participants with, than without, PCOS. Studies controlling for BMI showed a
      smaller difference between women with PCOS and controls on anxiety and depression
      scores than studies not controlling for BMI. CONCLUSIONS: Women with PCOS on
      average tend to experience mildly elevated anxiety and depression, significantly
      more than women without PCOS. Women with PCOS with lower BMI tended to have
      slightly lower anxiety and depression scores, suggesting that having a lower BMI
      reduces anxiety and depression. Future studies might consider (i) controlling for
      BMI, (ii) stratifying by medication use in order to control for any anti
      androgenic effects of medication and (iii) excluding women with polycystic
      ovaries from control groups.

PMID- 21725074
TI  - Co-expression of two distinct polysialic acids, alpha2,8- and alpha2,9-linked
      polymers of N-acetylneuraminic acid, in distinct glycoproteins and glycolipids in
      sea urchin sperm.
AB  - Naturally occurring polysialic acid (polySia) structures have a large diversity,
      primarily arising from the diversity in the sialic acid components as well as in
      the intersialyl linkages. In 2004, we demonstrated the presence of a new type of
      polySia, 8-O-sulfated N-acetylneuraminic acid (Neu5Ac) capped alpha2,9-linked
      polyNeu5Ac, on the O-glycans of a major 40-80 kDa sialoglycoprotein,
      flagellasialin, in sea urchin sperm. In this study, we demonstrated that another
      type of polySia, the alpha2,8-linked polyNeu5Ac, exclusively occurs on O-glycans
      of a 190 kDa glycoprotein (190 kDa-gp), whereas the alpha2,9-linked polyNeu5Ac is
      exclusively present on flagellasialin. The 190 kDa-gp is localized in both
      flagellum and head of sperm. We also demonstrated that polysialogangliosides
      containing the alpha2,8-linked polyNeu5Ac are present in sperm head. Thus, this
      study shows two novel features of the occurrence of polySia in nature, the co
      localization of polySia with different intersialyl linkages, the alpha2,8- and
      alpha2,9-linkages, in a single cell and the occurrence of alpha2,8-linked
      polyNeu5Ac in glycolipids. Anti-alpha2,8-linked polyNeu5Ac antibody had no effect
      on fertilization, which contrasted with the previous results that anti-alpha2,9
      linked polyNeu5Ac antibody inhibited sperm motility and fertilization. Based on
      these properties, distinct functions of alpha2,8- and alpha2,9-polySia structures
      are implicated in fertilization.

PMID- 21725076
TI  - Radiation doses in a newly founded Interventional Cardiology department.
AB  - Coronary angiography (CA) and percutaneous transluminal coronary angioplasty
      (PTCA) radiation doses were investigated in a recently founded Interventional
      Cardiology (IC) department. The study includes 336 procedures (177 CAs and 159
      PTCAs) carried out with a Philips digital flat detector monoplane system. Patient
      dose was measured in terms of kerma-area product (KAP) and cumulative dose. Using
      appropriate conversion factors, peak skin dose (PSD) and effective dose (E) were
      estimated. Median values of KAP (Gy cm(2)), PSD (mGy) and E (mSv) were: 34 478
      and 6.1, respectively for CA and 80 885 and 14.4 for PTCA, within European and
      international reference levels. Only 1.5 % of patients received radiation dose
      over the 2 Gy threshold (PTCA procedures) for deterministic effects and none
      reported any skin effect. Radiation doses were within international standards and
      comparable with other radiological examinations. The percentage of the high-risk
      patients for radiation skin effects is extremely low.

PMID- 21725077
TI  - Evaluation of radiation dose during pacemaker implantations.
AB  - The purpose was to evaluate patient radiation doses and compare with other
      interventional procedures. One hundred and twenty-eight procedures were carried
      out with a recently installed mobile undercouch C-arm machine with a 23-cm
      diameter image intensifier. The radiation dose is provided by the X-ray machine,
      in terms of cumulative dose (CD). Kerma-Area product (KAP) was then estimated
      from CD and the X-ray field size. Other patient parameters recorded were patient
      weight, age, kilovolt, milliampere and fluoroscopy time (T). Median (range) CD,
      KAP and T were 15.2 mGy (3.2-110 mGy), 6.3 Gy cm(2) (1.3-45.7 Gy cm(2)) and 5.2
      (1.5-27.4 min) min, respectively. Median E was 1.1 mSv (conversion factor: 0.18
      mSv per Gy cm(2)), which corresponds to approximately one lumbar spine X-ray
      radiography. The effective dose is much lower than a coronary angiography (8 mSv)
      or an electrophysiology study (6 mSv). Radiation dose is low compared with other
      interventional cardiology procedures.

PMID- 21725078
TI  - DS86 and DS02 organ dose calculations.
AB  - A brief review of the techniques used to calculate organ doses for the atomic
      bomb survivors at Hiroshima and Nagasaki is provided using the original dosimetry
      system 1986 (DS86) and revised dosimetry system 2002 (DS02). The DS02 study was
      undertaken to address a serious discrepancy between calculated and measured
      values for neutron activation at Hiroshima that had caused a lack of confidence
      in the previous dosimetry, designated as DS86. Some potential improvements to the
      organ dose calculations that were not considered during the DS02 study due to
      time and funding limitations are recommended in this paper.

PMID- 21725079
TI  - Global view on radiation protection in medicine.
AB  - When planning good management of ionising radiation in medicine, key factors such
      as ensuring that health professionals work together and convincing them that
      radiation protection (RP) represents a substantial part of the quality management
      system in their clinical practice are of utmost importance. The United Nations
      Scientific Committee on the Effects of Atomic Radiation has decided that one of
      the thematic priorities will be medical radiation exposure of patients. The
      International Commission on Radiological Protection has recently updated the
      report on RP in medicine and continues to work on focused documents centred on
      specific areas where advice is needed. The roles of the International Atomic
      Energy Agency, World Health Organization and the European Commission, in the area
      of RP in medicine, are described in the present document. The industry, the
      standardisation organisations as well as many scientific and professional
      societies are also dedicating significant effort to radiation safety aspects in
      medicine. Some of the efforts and priorities contemplated in RP in medicine over
      the coming years are suggested. The best outcome will be accomplished when all
      the actors, i.e. medical doctors, other health professionals, regulators, health
      authorities and the industry manage to work together.

PMID- 21725080
TI  - Radiation dose management in CT, SPECT/CT and PET/CT techniques.
AB  - New imaging technologies utilising X rays and radiopharmaceuticals are
      continuously under development. The benefit of computed tomography (CT) has been
      so dramatic that there is a tendency to overuse it and not to place enough
      efforts into optimisation of the technique. It is also now more and more common
      to combine two imaging techniques into a single investigation, such as PET/CT and
      SPECT/CT--the so-called 'hybrid imaging'. The increasing radiation exposure from
      CT has been of concern for some years and is now receiving increased attention
      from health professionals, authorities, manufacturers and patient groups. The
      relatively high radiation doses from PET and SPECT investigations have only
      recently been discussed. The aim of this article is to provide information on
      developing technologies and clinical techniques for 3D imaging using ionising
      radiation and their associated radiation dose to patients and staff. Tools for
      improved dose management are also discussed.

PMID- 21725081
TI  - Status of radiation protection in interventional cardiology in four East European
      countries.
AB  - Level of staff and patient radiation protection in interventional cardiology in
      four counties (Bosnia and Herzegovina, Croatia, Montenegro and Serbia) as a part
      of International Atomic Energy Agency project (RER/9/093) are presented. Patient
      doses were assessed in terms of air kerma area product (KAP), peak skin dose
      (PSD) or air kerma at interventional reference point (K(IRP)). Results were
      available from nine hospitals: 775 patients for KAP, 157 for PSD and 437 for
      K(IRP). Eight centres reported KAP >100 Gy cm(2) and five centres reported values
      >200 Gy cm(2). From patients monitored in terms of PSD, 14 (9 %) had PSD >2 Gy
      and 6 (3 %) patients from those monitored in terms of K(IRP) had value >5 Gy,
      indicating risk of skin injury. The results indicate need for optimisation and
      dose monitoring in complex fluoroscopically guided cardiology interventions.

PMID- 21725082
TI  - Impact of the International Atomic Energy Agency (IAEA) actions on radiation
      protection of patients in many countries.
AB  - In the 1990s, there was a lack of information on patient doses in most developing
      countries. In 2004, the International Atomic Energy Agency initiated projects
      aimed at assessing 'how safe are patients in radiological procedures and how to
      make them safer'. The major obstacle was a lack of medical physicists with
      patient dosimetry skills and a lack of dosimetry facilities. Actions taken were
      such as to yield results within a short span of time and a number of publications
      with interesting findings. Results showed that while patient doses in radiography
      are largely within diagnostic reference levels (DRLs), poor image quality is
      rampant. In mammography, CT and interventional procedures, doses higher than DRLs
      were observed. Dose management actions were implemented and significant
      improvements emerged. Utilising existing manpower (physicists, regulators,
      radiographers, radiologists), preparing detailed guidelines and data collection
      forms, focussing training on acquiring dosimetry skills, a system of periodic
      reports with mentoring and motivating collaborations within each country are some
      of the reasons for the success of the project.

PMID- 21725083
TI  - Ethnicity and falls in older men: low rate of falls in Italian-born men in
      Australia.
AB  - BACKGROUND: past research suggests that fall rates in older persons may differ by
      ethnicity. The aim of this study was to compare the incidence of falls between
      older male Italian-born immigrants and their Australian-born counterparts.
      METHODS: this study analysed data from 335 Italian-born and 848 Australian-born
      men aged 70 years and over participating in the Concord Health and Ageing in Men
      Project (CHAMP). Prospective falls data were collected by 4 monthly phone calls
      (mean follow-up time: 26.7 months). Negative binomial regression compared falls
      incidence rate ratios (IRR) between the two groups of men. RESULTS: there were 37
      (11%) Italian-born men and 185 (22%) Australian-born men who had two or more
      falls during follow-up (P < 0.001). Negative binomial analysis demonstrated that
      Italian-born men had half the incidence rate of falls compared with Australian
      born men (IRR = 0.51, 95% CI = 0.38-0.67). After adjustment for falls risk
      factors, Italian-born men remained significantly less likely to fall with a 43%
      lower fall rate (IRR = 0.57, 95% CI = 0.39-0.85). CONCLUSION: older male Italian
      born immigrants are less likely to fall than their Australian-born counterparts.
      Differences in fall rates between the two groups are not explained by established
      falls risk factors.

PMID- 21725084
TI  - Prevention of type 1 diabetes.
AB  - INTRODUCTION/BACKGROUND: Type 1 diabetes is a chronic autoimmune condition
      characterized by destruction of insulin-producing beta cells within the
      pancreatic islets. It is associated with considerable morbidity and mortality.
      Incidence levels are rising worldwide. SOURCES OF DATA: Pubmed search (Nov 2010)
      using keywords: Type 1 diabetes, prevention, trials, immunotherapy. AREAS OF
      AGREEMENT: The causes of disease are multifactorial with genetic and
      environmental factors playing a part. There is a long pre-clinical period before
      the onset of overt symptoms, which may be amenable to therapeutic intervention to
      prevent disease. AREAS OF CONTROVERSY: The exact nature of causative
      environmental factors is unknown and much debated. Immunotherapeutic intervention
      may therefore represent the best option for disease prevention. GROWING POINTS:
      Enhancement of 'regulatory' immune mechanisms currently shows the most promise as
      an approach to disease prevention. AREAS TIMELY FOR DEVELOPING RESEARCH: Clinical
      trials of early immunotherapeutic intervention may be the answer to disease
      prevention.

PMID- 21725085
TI  - Food additives: an ethical evaluation.
AB  - BACKGROUND: Food additives are an integral part of the modern food system, but
      opinion polls showing most Europeans have worries about them imply an urgent need
      for ethical analysis of their use. SOURCES OF DATA: The existing literature on
      food ethics, safety assessment and animal testing. AREAS OF AGREEMENT: Food
      additives provide certain advantages in terms of many people's lifestyles. AREAS
      OF CONTROVERSY: There are disagreements about the appropriate application of the
      precautionary principle and of the value and ethical validity of animal tests in
      assessing human safety. GROWING POINTS: Most consumers have a poor understanding
      of the relative benefits and risks of additives, but concerns over food safety
      and animal testing remain high. AREAS TIMELY FOR DEVELOPING RESEARCH: Examining
      the impacts of food additives on consumer sovereignty, consumer health and on
      animals used in safety testing should allow a more informed debate about their
      appropriate uses.

PMID- 21725086
TI  - Stem cell-based therapy and regenerative approaches to diseases of the
      respiratory system.
AB  - INTRODUCTION: Despite treatment advances in many diseases of the respiratory
      system, outcome remains poor. SOURCES OF DATA: This systematic review (PubMed and
      Ovid) 'analyses stem cell (SC)-based therapy and regenerative medicine (RM)
      approaches as potential novel strategies for diseases of the respiratory system.
      Current preclinical research and ongoing clinical trials are presented and their
      potential clinical impact and routine application discussed. AREAS OF AGREEMENT:
      These approaches may represent a promising alternative therapy for otherwise
      irreversible respiratory diseases. Several experimental and initial clinical data
      now exist. AREAS OF CONTROVERSY: Type of SC, limits of tissue engineering, route
      of delivery, cell behaviour (differentiation, growth, co-stimulation or
      immunomodulation) and interaction with the human microenvironment upon
      implantation. GROWING POINTS: Investigating underlying pathways and mechanisms.
      Evaluating gene, epigenetic and protein regulation. Interaction with the
      environment under diseased and healthy conditions. Detecting approaches with
      significant scientific and clinical impact. AREAS TIMELY FOR DEVELOPING RESEARCH:
      The potential capacity of SC-based therapy and RM should be carefully
      investigated before their translation into clinical practice.

PMID- 21725087
TI  - Full-length Dengue virus RNA-dependent RNA polymerase-RNA/DNA complexes:
      stoichiometries, intrinsic affinities, cooperativities, base, and conformational
      specificities.
AB  - Fundamental aspects of interactions of the Dengue virus type 3 full-length
      polymerase with the single-stranded and double-stranded RNA and DNA have been
      quantitatively addressed. The polymerase exists as a monomer with an elongated
      shape in solution. In the absence of magnesium, the total site size of the
      polymerase-ssRNA complex is 26 +/- 2 nucleotides. In the presence of Mg(2+), the
      site size increases to 29 +/- 2 nucleotides, indicating that magnesium affects
      the enzyme global conformation. The enzyme shows a preference for the
      homopyrimidine ssRNAs. Positive cooperativity in the binding to homopurine ssRNAs
      indicates that the type of nucleic acid base dramatically affects the enzyme
      orientation in the complex. Both the intrinsic affinity and the cooperative
      interactions are accompanied by a net ion release. The polymerase binds the dsDNA
      with an affinity comparable with the ssRNAs affinity, indicating that the binding
      site has an open conformation in solution. The lack of detectable dsRNA or dsRNA
      DNA hybrid affinities indicates that the entry to the binding site is specific
      for the sugar-phosphate backbone and/or conformation of the duplex.

PMID- 21725088
TI  - N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggers MSH2 and Cdt2 protein
      dependent degradation of the cell cycle and mismatch repair (MMR) inhibitor
      protein p21Waf1/Cip1.
AB  - p21(Waf1/Cip1) protein levels respond to DNA damage; p21 is induced after
      ionizing radiation, but degraded after UV. p21 degradation after UV is necessary
      for optimal DNA repair, presumably because p21 inhibits nucleotide excision
      repair by blocking proliferating cell nuclear antigen (PCNA). Because p21 also
      inhibits DNA mismatch repair (MMR), we investigated how p21 levels respond to DNA
      alkylation by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which triggers the MMR
      system. We show that MNNG caused rapid degradation of p21, and this involved the
      ubiquitin ligase Cdt2 and the proteasome. p21 degradation further required MSH2
      but not MLH1. p21 mutants that cannot bind PCNA or cannot be ubiquitinated were
      resistant to MNNG. MNNG induced the formation of PCNA complexes with MSH6 and
      Cdt2. Finally, when p21 degradation was blocked, MNNG treatment resulted in
      reduced recruitment of MMR proteins to chromatin. This study describes a novel
      pathway that removes p21 to allow cells to efficiently activate the MMR system.

PMID- 21725090
TI  - A way forward for whistleblowing.

PMID- 21725089
TI  - Diurnal regulation of the early growth response 1 (Egr-1) protein expression by
      hepatocyte nuclear factor 4alpha (HNF4alpha) and small heterodimer partner (SHP)
      cross-talk in liver fibrosis.
AB  - Early growth response 1 (Egr-1) protein is a critical regulator of genes
      contributing to liver fibrosis; however, little is known about the upstream
      transcriptional factors that control its expression. Here we show that Egr-1
      expression is tightly regulated by nuclear receptor signaling. Hepatocyte nuclear
      factor 4alpha (HNF4alpha) activated the Egr-1 promoter through three DR1 response
      elements as identified by trans-activation assays. Deletion of these response
      elements or knockdown of HNF4alpha using siRNA largely abrogated Egr-1 promoter
      activation. HNF4alpha activity, as well as its enrichment on the Egr-1 promoter,
      were markedly repressed by small heterodimer partner (SHP) co-expression. Egr-1
      mRNA and protein were transiently induced by HNF4alpha. On the contrary,
      HNF4alpha siRNA reduced Egr-1 expression at both the mRNA and protein levels, and
      overexpression of SHP reversed these effects. Conversely, knockdown of SHP by
      siRNA elevated Egr-1 protein. Interestingly, Egr-1 mRNA exhibited diurnal
      fluctuation, which was synchronized to the cyclic expression of SHP and HNF4alpha
      after cells were released from serum shock. Unexpectedly, the levels of Egr-1
      mRNA and protein were highly up-regulated in Hnf4alpha(-/-) mice. Both HNF4alpha
      and Egr-1 expression were dramatically increased in SHP(-/-) mice with bile duct
      ligation and in human cirrhotic livers, which was inversely correlated with
      diminished SHP expression. In conclusion, our study revealed control network for
      Egr-1 expression through a feedback loop between SHP and HNF4alpha.

PMID- 21725091
TI  - Centres for Healthcare Improvement: solution to the quality problem.

PMID- 21725092
TI  - Whistleblowing and patient safety: the patient's or the profession's interests at
      stake?

PMID- 21725093
TI  - John and James Parkinson's first description of acute appendicitis and its
      associated complications of perforation and death.

PMID- 21725094
TI  - Denial of pregnancy: a literature review and discussion of ethical and legal
      issues.
AB  - Denial of pregnancy is an important condition that is more common than expected,
      with an incidence at 20 weeks gestation of approximately 1 in 475. The proportion
      of cases persisting until delivery is about 1 in 2500, a rate similar to that of
      eclampsia. Denial of pregnancy poses adverse consequences including psychological
      distress, unassisted delivery and neonaticide. It is difficult to predict which
      women will develop denial of pregnancy. There are a number of forms of denial of
      pregnancy, including psychotic and non-psychotic variants. Denial of pregnancy is
      a 'red flag' that should trigger referral for psychiatric assessment. A national
      registry may help to provide more information about this condition and implement
      appropriate care. This condition poses challenging legal and ethical issues
      including assessment of maternal capacity, evaluation of maternal (and possibly
      fetal) best interests and the possibility of detention in hospital.

PMID- 21725095
TI  - Misadventures to patients during surgical and medical care in England and Wales:
      an analysis of deaths and hospital episodes.
AB  - Objectives To estimate incidence of injury to patients attributed to
      misadventures during surgical and medical care by age group and to examine recent
      trends. Design Analysis of routine morbidity and mortality data categorized by
      the 9th and 10th revisions of the International Classification of Diseases.
      Participants Children 0-14 years and adults >=15 years. Setting England and Wales
      during 1999 to 2008 (hospital episodes) and 1979 to 2009 (deaths). Main outcome
      measures We calculated deaths per million person-years and per 1000 hospital
      episodes; hospital episodes per 100,000 person-years and per 100,000 procedures
      performed. Results The rate of death attributed to misadventures during surgical
      and medical care in patients aged 75 years and older was over 50 times (rate
      ratio 57.2; 95% confidence interval 38.3-85.3) higher than in children aged 1-14
      years. Estimated hospital episode rates were 20 times (RR 20.0; 18.9-21.2) higher
      in patients aged 75 years and older. Mortality attributed to misadventures
      declined from 1.1 (0.9-1.4) deaths per million person-years in 1979 to 0.4 (0.2
      0.6) in 2009. Hospital episodes of misadventures decreased between 1999 and 2008
      from 30.8 (29.9-31.8) episodes per 100,000 procedures to 23.25 (22.5-24.1), but
      increased from 7.8 (7.6-8.1) per 100,000 person-years to 9.8 (9.5-10.1).
      Conclusions Misadventures during surgical and medical care are an important cause
      of avoidable injury. Older patients appear to be at higher risk of experiencing
      and dying from misadventure. Interpretation of recent trends is limited by
      uncertainties regarding the consistency and coverage of coding.

PMID- 21725096
TI  - Cerebral tuberculoma and magnetic resonance imaging.

PMID- 21725097
TI  - Adolf Bingel's blinded, controlled comparison of different anti-diphtheritic sera
      in 1918.

PMID- 21725098
TI  - My working day: Jennifer Dixon.

PMID- 21725099
TI  - Clinical leadership and management in the NHS.

PMID- 21725101
TI  - Does the time frame between exercise influence the effectiveness of hydrotherapy
      for recovery?
AB  - An increase in research investigating recovery strategies has occurred alongside
      the increase in usage of recovery by elite athletes. Because there is
      inconsistent evidence regarding the benefits of recovery on performance, it is
      necessary to examine research design to identify possible strategies that enhance
      performance in different athlete settings. The purpose of this review is to
      examine available recovery literature specifically related to the time frame
      between performance assessments to identify considerations for both research
      design and practical use of recovery techniques.

PMID- 21725102
TI  - The effects of wearing undersized lower-body compression garments on endurance
      running performance.
AB  - PURPOSE: To examine whether wearing various size lower-body compression garments
      improves physiological and performance parameters related to endurance running in
      well-trained athletes. METHODS: Eleven well-trained middle-distance runners and
      triathletes (age: 28.4 +/- 10.0 y; height: 177.3 +/- 4.7 cm; body mass: 72.6 +/-
      8.0 kg; VO2max: 59.0 +/- 6.7 mL.kg-1.min-1) completed repeat progressive maximal
      tests (PMT) and time-to-exhaustion (TTE) tests at 90% VO2max wearing either
      manufacturer-recommended LBCG (rLBCG), undersized LBCG (uLBCG), or loose running
      shorts (CONT). During all exercise testing, several systemic and peripheral
      physiological measures were taken. RESULTS: The results indicated similar effects
      of wearing rLBCG and uLBCG compared with the control. Across the PMT, wearing
      either LBCG resulted in significantly (P < .05) increased oxygen consumption, O2
      pulse, and deoxyhemoglobin (HHb) and decreased running economy, oxyhemoglobin,
      and tissue oxygenation index (TOI) at low-intensity speeds (8-10 km.h-1). At
      higher speeds (12-18 km.h-1), wearing LBCG increased regional blood flow (nTHI)
      and HHb values, but significantly lowered heart rate and TOI. During the TTE,
      wearing either LBCG significantly (P < .05) increased HHb concentration, whereas
      wearing uLBCG also significantly (P < .05) increased nTHI. No improvement in
      endurance running performance was observed in either compression condition.
      CONCLUSION: The results suggest that wearing LBCG facilitated a small number of
      cardiorespiratory and peripheral physiological benefits that appeared mostly
      related to improvements in venous flow. However, these improvements appear
      trivial to athletes, as they did not correspond to any improvement in endurance
      running performance.

PMID- 21725103
TI  - Reduction in physical match performance at the start of the second half in elite
      soccer.
AB  - PURPOSE: Soccer referees' physical match performances at the start of the second
      half (46-60 min) were evaluated in relation to both the corresponding phase of
      the first half (0-15 min) and players' performances during the same match
      periods. METHODS: Match analysis data were collected (Prozone, UK) from 12 soccer
      referees on 152 English Premier League matches during the 2008/09 soccer season.
      Physical match performance categories for referees and players were total
      distance, high-speed running distance (speed >5.5 m/s), and sprinting distance
      (>7.0 m/s). The referees' heart rate was recorded from the start of their warm-up
      to the end of the match. The referees' average distances (in meters) from the
      ball and fouls were also calculated. RESULTS: No substantial differences were
      observed in duration (16:42 +/- 2:35 vs 16:27 +/- 1:00 min) or intensity (107 +/-
      11 vs 106 +/- 14 beats/ min) of the referees' preparation periods immediately
      before each half. Physical match performance was reduced during the initial phase
      of the second half when compared with the first half in both referees (effect
      sizes-standardized mean differences-0.19 to 0.73) and players (effect sizes 0.20
      to 1.01). The degree of the decreased performance was consistent between referees
      and players for total distance (4.7 m), high-speed running (1.5 m), and sprinting
      (1.1 m). The referees were closer to the ball (effect size 0.52) during the
      opening phase the second half. CONCLUSION: Given the similarity in the referees'
      preparation periods, it may be that the reduced physical match performances
      observed in soccer referees during the opening stages of the second half are a
      consequence of a slower tempo of play.

PMID- 21725104
TI  - Relationships between triathlon performance and pacing strategy during the run in
      an international competition.
AB  - PURPOSE: The purpose of the present study was to examine relationships between
      athlete's pacing strategies and running performance during an international
      triathlon competition. METHODS: Running split times for each of the 107 finishers
      of the 2009 European Triathlon Championships (42 females and 65 males) were
      determined with the use of a digital synchronized video analysis system. Five
      cameras were placed at various positions of the running circuit (4 laps of 2.42
      km). Running speed and an index of running speed variability (IRSVrace) were
      subsequently calculated over each section or running split. RESULTS: Mean running
      speed over the first 1272 m of lap 1 was 0.76 km.h-1 (+4.4%) and 1.00 km.h-1
      (+5.6%) faster than the mean running speed over the same section during the three
      last laps, for females and males, respectively (P < .001). A significant inverse
      correlation was observed between RSrace and IRSVrace for all triathletes (females
      r = -0.41, P = .009; males r = -0.65, P = .002; and whole population -0.76, P =
      .001). Females demonstrated higher IRSVrace compared with men (6.1 +/- 0.5 km.h-1
      and 4.0 +/- 1.4 km.h-1, for females and males, respectively, P = .001) due to
      greater decrease in running speed over uphill sections. CONCLUSIONS: Pacing
      during the run appears to play a key role in high-level triathlon performance.
      Elite triathletes should reduce their initial running speed during international
      competitions, even if high levels of motivation and direct opponents lead them to
      adopt an aggressive strategy.

PMID- 21725105
TI  - Do male 100-km ultra-marathoners overdrink?
AB  - PURPOSE: Fluid overload is considered a main risk factor for exercise-associated
      hyponatremia (EAH). The aim of this study was to investigate the incidence of EAH
      in ultra-runners at the 100 km ultra-run in Biel, Switzerland. METHODS: Pre- and
      postrace, body mass, urinary specific gravity, hemoglobin, hematocrit, plasma
      [Na+], and plasma volume were determined. RESULTS: Of the 145 finishers, seven
      runners (4.8%) developed asymptomatic EAH. While running, the athletes consumed a
      total of (median and interquartile ranges) 6.9 (5.1-8.8) L over the 100 km
      distance, equal to 0.58 (0.41-0.79) L/h. Fluid intake correlated negatively and
      significantly with race time (r = -.50, P < .0001). Body mass decreased, plasma
      [Na+] remained unchanged, hematocrit and hemoglobin decreased, and urinary
      specific gravity increased. Plasma volume increased by 4.6 (-2.3 to 12.8) %.
      Change in body mass correlated with both postrace plasma [Na+] and Delta plasma
      [Na+]. Postrace plasma [Na+] correlated to Delta plasma [Na+]. Fluid intake was
      associated neither with postrace plasma [Na+] nor with Delta plasma [Na+]. Fluid
      intake was related to Delta body mass (r = .21, P = .012), but not to postrace
      body mass. Fluid intake showed no correlation to Delta plasma volume. Change in
      plasma volume was associated with postrace [Na+]. CONCLUSIONS: Incidences of EAH
      in 100 km ultra-marathoners were lower compared with reports on marathoners. Body
      mass decreased, plasma volume increased, and plasma [Na+] was maintained. Since
      fluid intake was related neither to Delta plasma volume nor to Delta plasma
      [Na+], we assume that factors other than fluid intake maintained body fluid
      homeostasis.

PMID- 21725106
TI  - Influence of environmental temperature on 40 km cycling time-trial performance.
AB  - The purpose of this study was to examine the effect of environmental temperature
      on variability in power output, self-selected pacing strategies, and performance
      during a prolonged cycling time trial. Nine trained male cyclists randomly
      completed four 40 km cycling time trials in an environmental chamber at 17
      degrees C, 22 degrees C, 27 degrees C, and 32 degrees C (40% RH). During the time
      trials, heart rate, core body temperature, and power output were recorded. The
      variability in power output was assessed with the use of exposure variation
      analysis. Mean 40 km power output was significantly lower during 32 degrees C
      (309 +/- 35 W) compared with 17 degrees C (329 +/- 31 W), 22 degrees C (324 +/-
      34 W), and 27 degrees C (322 +/- 32 W). In addition, greater variability in power
      production was observed at 32 degrees C compared with 17 degrees C, as evidenced
      by a lower (P = .03) standard deviation of the exposure variation matrix (2.9 +/-
      0.5 vs 3.5 +/- 0.4 units, respectively). Core temperature was greater (P < .05)
      at 32 degrees C compared with 17 degrees C and 22 degrees C from 30 to 40 km, and
      the rate of rise in core temperature throughout the 40 km time trial was greater
      (P < .05) at 32 degrees C (0.06 +/- 0.04 degrees C.km-1) compared with 17 degrees
      C (0.05 +/- 0.05 degrees C.km-1). This study showed that time-trial performance
      is reduced under hot environmental conditions, and is associated with a shift in
      the composition of power output. These finding provide insight into the control
      of pacing strategies during exercise in the heat.

PMID- 21725107
TI  - The effects of fatigue on soccer skills performed during a soccer match
      simulation.
AB  - PURPOSE: This study examined the effects of exercise-induced fatigue on soccer
      skills performed throughout simulated match play. METHODS: Fifteen academy soccer
      players completed a soccer match simulation (SMS) including passing, dribbling,
      and shooting skills. Precision, success rate, and ball speed were determined via
      video analysis for all skills. Blood samples were obtained before exercise
      (preexercise), every 15 min during the simulation (15, 30, 45, 60, 75, and 90
      min), and 10 min into half-time. RESULTS: Preliminary testing confirmed test
      retest repeatability of performance, physiological, and metabolic responses to 45
      min of the SMS. Exercise influenced shooting precision (timing effect: P = .035)
      and passing speed (timing effect: P = .011), such that shots taken after exercise
      were 25.5 +/- 4.0% less accurate than those taken before exercise and passes in
      the last 15 min were 7.8 +/- 4.3% slower than in the first 15 min. Shot and pass
      speeds were slower during the second half compared with the first half (shooting:
      17.3 +/- 0.3 m.s-1 vs 16.6 +/- 0.3 m.s-1, P = 0.012; passing: 13.0 +/- 0.5 m.s-1
      vs 12.2 +/- 0.5 m.s-1, P = 0.039). Dribbling performance was unaffected by
      exercise. Blood lactate concentrations were elevated above preexercise values
      throughout exercise (time of sample effect: P < .001). CONCLUSIONS: These
      findings demonstrate that soccer-specific exercise influenced the quality of
      performance in gross motor skills, such as passing and shooting. Therefore,
      interventions to maintain skilled performance during the second half of soccer
      match play are warranted.

PMID- 21725108
TI  - Table tennis: cardiorespiratory and metabolic analysis of match and exercise in
      elite junior national players.
AB  - PURPOSE: The aim of the study was to determine the cardiorespiratory and
      metabolic characteristics during intense and moderate table tennis (TT) training,
      as well as during actual match play conditions. METHODS: Blood lactate
      concentration (Lac), heart rate (HR, beats per minute [bpm]), oxygen uptake
      (VO2), and energy expenditure (EE) in 7 male participants of the German junior
      national team (age: 14 +/- 1 y, weight: 60.5 +/- 5.6 kg height; 165 +/- 8 cm)
      were examined during six training sessions (TS) and during an international
      match. The VO2 was measured continuously with portable gas analyzers. Lac was
      assessed every 1 to 3 min during short breaks. RESULTS: Mean (peak) values for
      Lac, HR, VO2, and EE during the TS were 1.2 +/- 0.7 (4.5) mmol.L-1, 135 +/- 18
      (184) bpm, 23.5 +/- 7.3 (43.0) mL.kg-1. min-1, and 6.8 +/- 2.0 (11.2) METs,
      respectively. During match play, mean (peak) values were 1.1 +/- 0.2 (1.6) mmol.L
      1, 126 +/- 22 (189) bpm, 25.6 +/- 10.1 (45.9) mL.kg-1.min-1, and 4.8 +/- 1.4
      (9.6) METs, respectively. CONCLUSIONS: For the first time, cardiorespiratory and
      metabolic data in elite junior table tennis have been documented demonstrating
      low cardiorespiratory and metabolic demands during TT training and match play in
      internationally competing juniors.

PMID- 21725109
TI  - Influence of temperature and performance level on pacing a 161 km trail
      ultramarathon.
AB  - BACKGROUND: Even pacing has been recommended for optimal performances in running
      distances up to 100 km. Trail ultramarathons traverse varied terrain, which does
      not allow for even pacing. PURPOSE: This study examined differences in how
      runners of various abilities paced their efforts in the Western States Endurance
      Run (WSER), a 161 km trail ultramarathon in North America, under hot vs cooler
      temperatures. METHOD: Temperatures in 2006 (hot) and 2007 (cooler) ranged from 7
      38 degrees C and 2-30 degrees C, respectively. Arrival times at 13 checkpoints
      were recorded for 50 runners who finished the race in both years. After
      stratification into three groups based on finish time in 2007 (<22, 22-24, 24-30
      h), paired t tests were used to compare the difference in pace across checkpoints
      between the years within each group. The chi2 test was used to compare
      differences between the groups on the number of segments run slower in the hot vs
      cooler years. RESULTS: For all groups, mean pace across the entire 161 km race
      was slower in 2006 than in 2007 (9:23 +/- 1:13 min/km vs 8:42 +/- 1:15 min/km, P
      < .001) and the pace was slower from the start of the race when temperatures were
      still relatively cool. Overall, the <22 h cohort ran slower in 2006 than 2007
      over 12 of the 14 segments examined, the 22-24 h cohort was slower across 10 of
      the segments, and the >24 h cohort was slower across only 6 of the segments
      chi(2)2 = 6.00, P = .050). Comparable pacing between the 2 y corresponded with
      onset of nighttime and cooling temperatures. CONCLUSIONS: Extreme heat impairs
      all runners' ability to perform in 161 km ultramarathons, but faster runners are
      at a greater disadvantage compared with slower competitors because they complete
      a greater proportion of the race in the hotter conditions.

PMID- 21725110
TI  - The construct validity of session RPE during an intensive camp in young male
      Taekwondo athletes.
AB  - PURPOSE: The session rating of perceived exertion (RPE) is a practical and
      noninvasive method that allows a quantification of the internal training load
      (TL) in individual and team sports, but no study has investigated its construct
      validity in martial arts. Therefore, the purpose of this study was to examine the
      convergent validity between the session-RPE method and two objective HR-based
      methods for quantifying the similar TL during a high-TL camp in young Taekwondo
      (TKD) athletes. METHODS: Ten young TKD athletes (mean +/- SD: age, 13.1 +/- 2.4
      y; body mass, 46.1 +/- 12.7 kg; height, 1.53 +/- 0.15 m; maximum heart rate
      (HRmax), 201.0 +/- 8.2 bpm) participated in this study. During the training
      period, subjects performed 35 TKD training sessions, including two formal
      competitions during which RPE and HR were recorded and analyzed (308 individual
      training sessions). Correlation analysis was used to evaluate the convergent
      validity between session-RPE method and the two commonly used HR-based methods
      for assessing TL in a variety of training modes. RESULTS: Significant
      relationships were found between individual session-RPE and all the HR-based TLs
      (r values from 0.55 to 0.90; P < .001). Significant correlations were observed in
      all mode of exercises practiced in TKD. CONCLUSIONS: This study shows that
      session-RPE can be considered as a valid method to assess TL in TKD.

PMID- 21725111
TI  - Seasonal monitoring of sprint and jump performance in a soccer youth academy.
AB  - PURPOSE: The aim of the study was to longitudinally assess speed and jump
      performance characteristics of youth football players over a 3 y period. METHODS:
      Two hundred players across five age squads (U12-U16) from an English Football
      League academy participated. Sprint performance (10 and 30 m) and countermovement
      jump height were assessed at 6 mo intervals. Pairwise analyses determined the
      level of change in performance between consecutive intervals. RESULTS: Sprint
      performance changes tended to be greatest during the early teenage years, with
      observed changes exceeding the smallest worthwhile effect (1.0% for 10 and 30 m
      sprints). Changes in jump performance were above the smallest worthwhile effect
      of 1.8% for all but one interval. Large individual variability in the magnitude
      of change in sprint and jump performance, perhaps due to the confounding effect
      of growth and maturation, revealed few significant differences across the 6 mo
      intervals. Cumulative changes in performance demonstrated strong linear
      relationships, with a yearly rate of change of 6.9% for jump height, and 3.1 and
      2.7% for 10 m and 30 m sprint time respectively. The magnitude of change in
      performance tended not to differ from one interval to another. CONCLUSIONS: The
      results of this study may primarily be used to monitor and predict the rate of
      progression of youth football players. In addition, these results may be used as
      a benchmark to evaluate the effectiveness of a current training program.

PMID- 21725112
TI  - Using modeling to understand how athletes in different disciplines solve the same
      problem: swimming versus running versus speed skating.
AB  - Every new competitive season offers excellent examples of human locomotor
      abilities, regardless of the sport. As a natural consequence of competitions,
      world records are broken every now and then. World record races not only offer
      spectators the pleasure of watching very talented and highly trained athletes
      performing muscular tasks with remarkable skill, but also represent natural
      models of the ultimate expression of human integrated muscle biology, through
      strength, speed, or endurance performances. Given that humans may be approaching
      our species limit for muscular power output, interest in how athletes improve on
      world records has led to interest in the strategy of how limited energetic
      resources are best expended over a race. World record performances may also shed
      light on how athletes in different events solve exactly the same problem
      minimizing the time required to reach the finish line. We have previously applied
      mathematical modeling to the understanding of world record performances in terms
      of improvements in facilities/equipment and improvements in the athletes'
      physical capacities. In this commentary, we attempt to demonstrate that
      differences in world record performances in various sports can be explained using
      a very simple modeling process.

PMID- 21725113
TI  - Changes in a top-level soccer referee's training, match activities, and
      physiology over an 8-year period: a case study.
AB  - Athlete case studies have often focused on the training outcome and not the
      training process. Consequently, there is a dearth of information detailing
      longitudinal training protocols, yet it is the combined assessment of both
      outcome and process that enhances the interpretation of physical test data. We
      were provided with a unique opportunity to assess the training load, physical
      match performance, and physiological fitness of an elite soccer referee from the
      referee's final season before attaining full-time, professional status (2002)
      until the season when he refereed the 2010 UEFA Champions League and FIFA World
      Cup finals. An increased focus on on-field speed and gym-based strength training
      was observed toward the end of the study period and longitudinal match data
      showed a tendency for decreased total distances but an increased intensity of
      movements. Laboratory assessments demonstrated that VO2max remained stable (52.3
      vs 50.8 mL.kg-1.min-1), whereas running speed at the lactate threshold (14.0 vs
      12.0 km.h-1) and running economy (37.3 vs 43.4 mL.kg-1.min-1) both improved in
      2010 compared with 2002.

PMID- 21725114
TI  - Evidence-based practice and research: a challenge to the development of adapted
      physical activity.
AB  - Evidence-based practice (EBP) is a growing movement in the health and educational
      disciplines that recommends emphasis on research outcomes during decision making
      in practice. EBP is made possible through evidence based research (EBR), which
      attempts to synthesize the volume and scientific rigor of intervention
      effectiveness. With the purpose of assessing the impact of this movement on
      adapted physical activity, this article (a) describes EBP/EBR and outlines its
      methodological development, (b) provides an historical perspective of EBP/EBR in
      APA, (c) examines EBR quality indicators in the review literature published in
      Adapted Physical Activity Quarterly, (d) identifies and synthesizes thematic
      domains appearing in these review articles, and (e) discusses practical examples
      of professional issues in APA arising from a lack of EBR.

PMID- 21725115
TI  - Motor skill interventions to improve fundamental movement skills of preschoolers
      with developmental delay.
AB  - Preschoolers with developmental delay (DD) are at risk for poor fundamental
      movement skills (FMS), but a paucity of early FMS interventions exist. The
      purpose of this review was to critically appraise the existing interventions to
      establish direction for future trials targeting preschoolers with DD. A total of
      11 studies met the inclusion criteria. Major findings were summarized based on
      common subtopics of overall intervention effect, locomotor skill outcomes, object
      control outcomes, and gender differences. Trials ranged from 8 to 24 weeks and
      offered 540-1700 min of instruction. The majority of trials (n = 9) significantly
      improved FMS of preschoolers with DD, with a large intervention effect (eta(2) =
      0.57-0.85). This review supports the utility of interventions to improve FMS of
      preschoolers with DD. Future researchers are encouraged to include more robust
      designs, a theoretical framework, and involvement of parents and teachers in the
      delivery of the intervention.

PMID- 21725116
TI  - Athletic identity, sport participation, and psychological adjustment in people
      with spinal cord injury.
AB  - This study examined interrelationships among athletic identity, sport
      participation, and psychological adjustment in a sample of people with spinal
      cord injury (SCI). Participants (N = 1,034) completed measures of athletic
      identity, life satisfaction, anxiety, depression, and demographic and sport
      participation variables. Current amount of weekly sport participation was
      positively related to athletic identity when statistically controlling for age,
      gender, and pre-SCI amount of weekly sport participation. Being able to practice
      one's favorite sport after SCI was associated with higher levels of athletic
      identity and better psychological adjustment. Team sport participants reported
      experiencing better psychological adjustment than individual sport participants
      did. The findings suggest that social factors are important in the link between
      sport participation and psychological adjustment in people with SCI.

PMID- 21725117
TI  - Differences in soccer kick kinematics between blind players and controls.
AB  - The purpose of the current study was to examine the kinematic differences during
      instep soccer kicks between players who were blind and sighted controls. Eleven
      male soccer players who were blind and nine male sighted performed instep kicks
      under static and dynamic conditions. The results indicated significantly higher
      (p < .05) ball speed velocities (20.81m/sec) and ball/foot speed ratio values
      (1.35) for soccer players who were blind during the static kick compared with
      sighted players (16.16m/sec and 1.23, respectively). Significant group effect on
      shank and foot angular velocity was observed during the static kicking condition
      (p < .05), while no differences were found during the dynamic kicking condition
      (p > .05). Despite the absence of vision, systematic training could have
      beneficial effects on technical skills, allowing athletes who are blind to
      develop skill levels comparable to sighted athletes.

PMID- 21725118
TI  - Is increased residual shank length a competitive advantage for elite transtibial
      amputee long jumpers?
AB  - The purpose of this study was to evaluate the extent to which residual shank
      length affects long jump performance of elite athletes with a unilateral
      transtibial amputation. Sixteen elite, male, long jumpers with a transtibial
      amputation were videoed while competing in major championships (World
      Championships 1998, 2002 and Paralympic Games, 2004). The approach, take-off, and
      landing of each athlete's best jump was digitized to determine residual and
      intact shank lengths, jump distance, and horizontal and vertical velocity of
      center of mass at touchdown. Residual shank length ranged from 15 cm to 38 cm.
      There were weak, nonsignificant relationships between residual shank length and
      (a) distance jumped (r = 0.30), (b) horizontal velocity (r = 0.31), and vertical
      velocity (r = 0.05). Based on these results, residual shank length is not an
      important determinant of long jump performance, and it is therefore appropriate
      that all long jumpers with transtibial amputation compete in the same class. The
      relationship between residual shank length and key performance variables was
      stronger among athletes that jumped off their prosthetic leg (N = 5), and
      although this result must be interpreted cautiously, it indicates the need for
      further research.

PMID- 21725119
TI  - In vivo virtual histology intravascular ultrasound comparison of neointimal
      hyperplasia within drug-eluting- versus bare metal stents.
AB  - BACKGROUND: The process of in-stent neointimal hyperplasia (NIH) between drug
      eluting stents (DES) and bare metal stents (BMS) might be different. We compared
      in vivo composition of in-stent NIH between DES and BMS using virtual histology
      intravascular ultrasound (VH-IVUS). METHODS AND RESULTS: Volumetric VH-IVUS was
      used to compare in-stent NIH between 23 DES and 15 BMS in 30 patients who
      underwent coronary angiography because of angina. The inner and outer VH-IVUS
      contours were drawn in a way to avoid the stent strut artifacts. Cross-sectional
      analysis was done at every VH-IVUS frame within the stent, thereby allowing
      volumetric measurement of stent, lumen, and NIH and its components. Baseline
      characteristics and IVUS measurements were similar between DES and BMS groups.
      The duration of follow-up was similar between DES (median 38 months
      [interquartile range, 7-59]) vs. BMS (median 40 months [interquartile range, 7
      99]), (p=0.26). % necrotic core (NC) volume was significantly higher in DES than
      BMS: 19.5 [16.3, 25.6] vs. 12.1 [8.2, 18.5] (p=0.006). %NC volume significantly
      increased with time in BMS (p=0.007), but not in DES (p=0.24) so that at any
      given time point, %NC in DES was greater than in BMS. After adjustment for
      baseline differences, only DES (p=0.003) and stent age (p=0.043) were independent
      predictors of %NC volume. VH-IVUS in-stent thin-cap fibroatheromas were detected
      only in the DES group: 34.8% vs. 0%, p=0.013. CONCLUSION: In vivo composition of
      in-stent NIH between DES and BMS was different, suggesting that the process of in
      stent NIH in DES and BMS is diverse.

PMID- 21725120
TI  - Tissue removal by ultrasound evaluation (the TRUE study): the Jetstream G2 system
      post-market peripheral vascular IVUS study.
AB  - BACKGROUND: Balloon angioplasty and stenting of infra-inguinal lesions is limited
      by poor long-term patency rates. Atherectomy decreases plaque burden and provides
      an alternative means of revascularizing patients with peripheral arterial
      disease. The Jetstream G2TM (Pathway Medical Technologies, Inc., Kirkland,
      Washington) is a newer rotational aspiration atherectomy device, uniquely
      combining rotablation with aspiration capability. We evaluated the debulking
      properties of this device by analyzing changes in the plaque volume and
      composition and vessel size using intravascular ultrasound (IVUS) and virtual
      histology (VH). Freedom from target lesion revascularization (TLR) at 6 and 12
      months was also evaluated. METHODS AND RESULTS: Eighteen patients with peripheral
      arterial disease requiring intervention (severe claudication despite optimal
      medical treatment or critical limb ischemia) were treated with rotational
      atherectomy. The mean age was 69.6 +/- 11 years, 66.7% were male, and 44.4% had
      diabetes. The mean total plaque volume decreased by 56.6 mm3 (479.8 +/- 172.5 mm3
      to 423.2 +/- 156.6 mm3; p < 0.0001), which resulted in a mean luminal volume
      increase of 64.3 mm3 (148.4 +/- 84.1 mm3 to 212.7 +/- 72.1 mm3; p < 0.0001). This
      was achieved without significant Dotter effect with either technique, as
      evidenced by the virtually unchanged vessel volume before and after treatment
      (628.3 +/- 158.5 mm3 and 635.9 +/- 169.0 mm3, respectively; p = 0.22). There was
      a significant reduction in fibrotic and fibro-fatty plaque volume, with no
      appreciable effect on necrotic core and dense calcium. There were no reported
      procedure-related complications and the 6- and 12-month TLR rate was 11% (2/18).
      CONCLUSION: Atherectomy with the Jetstream G2 system results in substantial
      plaque volume reduction by removing fibrotic and fibro-fatty plaque. This
      resulted in substantial luminal volume expansion without concomitant vessel
      expansion. There were no major procedure-related complications, along with a
      relatively low 6- and 12-month rate of TLR. Future studies involving a larger
      number of patients are warranted to examine the potential clinical benefits of
      this promising technology.

PMID- 21725121
TI  - Virtual histologic guidance of percutaneous peripheral atherectomy: the evolution
      of a new paradigm?

PMID- 21725122
TI  - Details of left ventricular remodeling and the mechanism of paradoxical
      ventricular septal motion after coronary artery bypass graft surgery.
AB  - OBJECTIVE: The purpose of this study was to obtain new details of three
      dimensional left ventricular wall motion related to ventricular remodeling in
      patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Cardiac
      gated, phase-contrast measurements using navigator-gated, high temporal
      resolution, tissue phase mapping were obtained on 19 patients (66 +/- 7 years
      old) before and after CABG. Left ventricular motion patterns and myocardial
      velocities were recorded for radial, circumferential and longitudinal motion.
      Radial, circumferential and longitudinal velocity curves were obtained separately
      for 16 ventricular segments. Ventricular torsion rate and longitudinal strain
      rate were also derived pre- and post-surgery. RESULTS: After CABG, there was a
      significant improvement in apical contraction, with an apparent paradoxical
      decrease in the radial inward motion of the septal segments at the left
      ventricular base. Despite improved ventricular contractility during systole, peak
      longitudinal and rotational velocities decreased or showed no significant
      changes. An altered pattern of rotational motion with decreased initial counter
      clockwise rotation at the beginning of systole and subsequent lower amplitude of
      reversed motions in diastole was also noted in most left ventricular segments.
      Lower peak clockwise rotational velocities were recorded in the basal
      anteroseptal segment with relatively higher values in the rest of the basal
      segments. CONCLUSION: Our results suggest that post-operative changes after CABG
      are limiting ventricular rotational and longitudinal motions, despite an increase
      in ventricular contractility due to revascularization. At the ventricular base,
      the restrained rotational motion of basal anteroseptal segment, located
      proximally to the right ventricular insertion, and higher rotational velocities
      of the rest of the segments are pushing the septum toward the right ventricle
      during ventricular twisting. At the ventricular apex, the restrain in rotational
      motion caused by post-operative adhesions is affecting all apical segments due to
      a much smaller left ventricular diameter at this level. The rotating apex and the
      apical septum are similarly displaced toward the right ventricle during
      ventricular twisting.

PMID- 21725123
TI  - Cardiac events after non-cardiac surgery in patients with previous coronary
      intervention in the drug-eluting stent era.
AB  - The peri-operative risk for patients with coronary drug-eluting stents (DES) who
      subsequently have non-cardiac surgery (NCS) is unclear. We performed this
      retrospective study of all patients in our institution who had coronary
      intervention and subsequent NCS from 2003 through December 2008 to evaluate the
      incidence of major adverse cardiac events (MACE) in patients who received DES
      compared to those who received bare-metal stents (BMS) or had percutaneous
      transluminal coronary angioplasty (PTCA) during the same time period. The main
      outcome measures were 30-day post-operative myocardial infarction, stent
      thrombosis, target vessel revascularization (TVR) and cardiac death. During the 6
      year study period, 1,770 coronary interventions were performed and 238 patients
      subsequently had NCS in 8 days to 49 months. Eighteen patients had PTCA, 79 BMS
      and 141 DES. Acute myocardial infarction occurred in 1 patient who had PTCA, 2
      who had BMS and 14 who had DES (p = 0.10). Stent thrombosis occurred in 6
      patients who had DES and none who had BMS (p = 0.09). Seven patients who had DES
      had TVR compared to 1 patient who had BMS and none who had PTCA (p = 0.41).
      Cardiac mortality occurred in 2 patients who had DES and none who had PTCA or BMS
      (p = 0.35). In conclusion, the 30-day MACE in patients who received coronary DES
      and undergone NCS were not significantly different compared to those who received
      BMS or had PTCA only, with a trend toward higher stent thrombosis in the DES
      group.

PMID- 21725124
TI  - Drug-eluting stents and non-cardiac surgery: learning lessons the hard way.

PMID- 21725125
TI  - Applications of the distal anchoring technique in coronary and peripheral
      interventions.
AB  - The distal balloon anchoring technique involves inflation of a balloon distal to
      or at a target lesion to facilitate equipment delivery. We report various
      applications of this technique to facilitate complex coronary and peripheral
      arterial interventions.

PMID- 21725126
TI  - Distal anchoring technique: yet another weapon for successful intervention.

PMID- 21725127
TI  - Successful stent implantation guided by intravascular ultrasound and a Doppler
      guidewire without contrast injection in a patient with allergy to iodinated
      contrast media.
AB  - Presence of allergy to iodinated contrast may prevent percutaneous coronary
      intervention (PCI) to be performed. We present a 76-year-old male with a history
      of allergic reaction to iodinated contrast who successfully underwent
      intravascular ultrasound (IVUS) and a Doppler guidewire-guided PCI. Stent size
      was determined based on IVUS. After PCI, stent expansion and a lack of edge
      dissection or incomplete apposition were confirmed by IVUS and a good antegrade
      coronary flow was confirmed by a Doppler guidewire. Thus, PCI without contrast
      injection under IVUS and a Doppler guidewire-guidance may be feasible in selected
      patients with allergy to iodinated contrast.

PMID- 21725128
TI  - Subacute stent thrombosis owing to complete clopidogrel resistance successfully
      managed with prasugrel.
AB  - This report describes a case of an acute anterior myocardial infarction secondary
      to subacute stent thrombosis of a drug-eluting stent within the proximal segment
      of the left anterior descending artery (LAD) 5 days after percutaneous
      transluminal coronary angioplasty and stenting (PCI). The patient was initially
      managed with conventional dual-antiplatelet therapy (aspirin and clopidogrel) and
      was subsequently found to have complete absence of adenosine diphosphate (ADP)
      receptor P2Y12 receptor inhibition. Following additional PCI of the LAD and
      substitution of clopidogrel for the thienopyridine prasugrel, therapeutic
      platelet inhibition was achieved without recurrence of stent thrombosis.

PMID- 21725129
TI  - An atypical case of acute myocardial infarction.
AB  - Most ST-elevation myocardial infarctions are related to atherothrombosis and
      benefit from emergent percutaneous coronary intervention. On the other hand, type
      A aortic dissection is a less frequent but deadly disease requiring emergent
      surgery. In the present case, we aimed to report the case of a patient who
      presented with aortic dissection responsible for STEMI and cardiogenic shock
      related to a compressive hematoma of the left main trunk. This atypical case
      underlines the need for careful assessment of the aorta in case of left main
      trunk occlusion in patients without evidence of atheroma in the other coronary
      segment. Unfortunately, in this case, refractory cardiogenic shock postponed
      surgical repair and led to the patient's death.

PMID- 21725130
TI  - Transient coronary aneurysm formation after NevoTM stent implantation versus
      persistent coronary aneurysm after Cypher SelectTM stent implantation.
AB  - We implanted a Cypher SelectTM coronary stent and two months later a NevoTM
      sirolimus-eluting coronary stent in another vessel. At a prescheduled
      angiographic follow-up, coronary aneurysms were seen in the two stented segments,
      6 and 8 months after stent implantation, respectively. Six months later, the
      aneurysm had healed in the Nevo, but was still present in the Cypher stented
      segment. We hypothesize that aneurysm formation was induced by sirolimus and the
      polymer of the implanted stents, and that subsequent healing was possible in the
      Nevo stent after degradation of the polymer.

PMID- 21725131
TI  - Novel microsnare successfully used to remove small debris from the right coronary
      artery.
AB  - Soutenir (Asahi-Intecc, Nagoya, Japan), a novel microsnare, was used to grip and
      pull a retrograde guidewire through arteries with chronic total occlusions during
      percutaneous coronary intervention (PCI). Soutenir can pass through a
      microcatheter with a 0.020" lumen, and it can easily enter distal lesions in the
      coronary artery. Here, we introduce a method for retrieving the tip of a broken
      intravascular ultrasound (IVUS) catheter by using this microsnare. We present the
      case of a 64-year-old man who was referred to our hospital for narrowing of the
      proximal right coronary artery (RCA). After IVUS examination, the catheter was
      removed from the artery with some difficulty, and the catheter tip broke. The
      broken tip remained in the RCA and was carried along with the blood to the distal
      part of the RCA. The conventional gooseneck snare and filter device failed to
      retrieve the broken tip. However, Soutenir easily passed beyond the catheter tip
      and reached the distal part of the atrioventricular branch. It snared the tip of
      the catheter, whereby the tip could easily be removed. Thus, without damaging the
      RCA, we successfully removed the broken catheter tip from the RCA using this
      microsnare.

PMID- 21725132
TI  - Antegrade ballooning with retrograde approach for the treatment of long
      restenotic total occlusion.
AB  - A retrograde approach through collateral channels is thought to improve the
      success rate of percutaneous coronary intervention for chronic total coronary
      occlusion (CTO). Among CTO lesions, the in-stent chronic total reocclusion (ISR
      CTO) is a subset with an unsatisfactory outcome despite repeated procedures.
      Various strategies and techniques are required to improve the success rate of
      this novel approach. We describe a case in which a long ISR-CTO was successfully
      recanalized by a drug-eluting balloon after antegrade ballooning of the proximal
      part of the lesion with retrograde wire crossing, and discuss the availability of
      this approach for the treatment of long ISR-CTO.

PMID- 21725133
TI  - Sinus tachycardia as a first sign of aortic dissection.
AB  - Aortic dissection is an uncommon and often life-threatening condition. It usually
      presents with classic symptoms, such as severe tearing chest pain radiating to
      the back associated with acute hemodynamic compromise. Painless aortic dissection
      is often an under-recognized entity. Its incidence is low, but represents an
      important clinical dilemma that requires physician vigilance and awareness to
      diagnose and quickly treat patients to decrease the mortality rate. We present
      the case of a patient with prostate cancer on chemotherapy, who was referred to
      the emergency room from the oncology clinic because he was found to be
      tachycardiac without any other major complaints on routine clinical visit.
      Electrocardiogram showed sinus tachycardia. Computed tomography was performed to
      rule out pulmonary embolus, and revealed acute aortic rupture into the
      pericardial space and manifesting as pericardial tamponade.

PMID- 21725134
TI  - Percutaneous coronary vein angioplasty for severe spasm of the posterolateral
      vein during bi-ventricular pacing.
AB  - Coronary venous spasm is an under-recognized and often reversible technical
      challenge that may be encountered while placing bi-ventricular pacing devices. We
      describe a case of severe vasopsam in the posterolateral left ventricular vein
      that was managed by balloon angioplasty, followed by successful placement of the
      left ventricular lead.

PMID- 21725135
TI  - Percutaneous retrieval of entrapped partially inflated broken coronary
      angioplasty balloon by modified Fogarty technique.
AB  - The optimal approach in managing cases complicated due to retained components in
      the coronary arteries during angioplasty is still not clear. In most cases,
      management is individualized. We report the retrieval of a partially inflated
      balloon with a broken shaft from the coronary system using a simple technique
      based on Fogarty. This did not involve the use of a snare or any other retrieval
      tool.

PMID- 21725136
TI  - Coronary to pulmonary artery fistulas: an incidental finding with challenging
      therapeutic options.
AB  - We report the incidental finding of 2 coronary to pulmonary artery fistulas
      observed at coronary angiography performed in a 48-year-old man presenting with
      acute inferior ST-elevation myocardial infarction (STEMI). Coronary angiography
      revealed an acute thrombotic occlusion of the mid segment of the right coronary
      artery (RCA), which was treated with thromboaspiration and bare-metal stenting.
      Significant stenoses of the left anterior descending (LAD) and left circumflex
      (LCX) arteries were also observed during angiography, as well as the presence of
      2 large coronary to pulmonary artery fistulas, one originating from the proximal
      LAD and the other from the ostial RCA. The clinical evolution was uneventful and
      the patient underwent successful coronary bypass grafting of the LAD and LCX
      lesions associated with ligation of the coronary artery fistulas 6 weeks later.
      The fact that 2 large coronary to pulmonary artery fistulas were observed during
      an acute coronary syndrome in a previously asymptomatic patient with extensive
      coronary artery disease is of particular interest, because it allowed early
      surgical correction of this rare inborn coronary anomaly before the development
      of late and irreversible left ventricular dysfunction.

PMID- 21725137
TI  - Collateralization of an occluded left internal mammary artery coronary bypass
      graft.
AB  - The left internal mammary artery (LIMA) is frequently utilized in coronary artery
      bypass grafting (CABG); adequate visualization of the LIMA bypass graft during
      diagnostic angiography is critical for determination of myocardial blood supply.
      We present a novel case of angiography via a left transradial approach
      demonstrating an occluded LIMA coronary bypass graft with antegrade flow
      maintained via a collateral branch from the ipsilateral thyrocervical trunk.
      Given the prevalence of LIMA use in CABG, it is critical to be aware of unusual
      configurations, including collateralization of a proximally occluded LIMA graft
      as described in this report.

PMID- 21725138
TI  - Targeting invadopodia to block breast cancer metastasis.
AB  - Better understanding the mechanisms underlying the metastatic process is
      essential to developing novel targeted therapeutics. Recently, invadopodia have
      been increasingly recognized as important drivers of local invasion in
      metastasis. Invadopodia are basally-localized, actin-rich structures that
      concentrate protease activity to areas of the cell in contact with the
      extracellular matrix. We recently found that the transcription factor Twist1, a
      central regulator of the epithelial-mesenchymal transition (EMT), promotes
      invadopodia formation via upregulation of platelet-derived growth factor receptor
      (PDGFR) expression and activity. This finding, combined with other investigations
      into the mechanisms of invadopodia formation, reveal several novel targets for
      clinical inhibition of invadopodia. Here, we provide an overview of clinically
      relevant targets for intervention in invadopodia, including Src signaling, PDGFR
      signaling, and metalloprotease activity.

PMID- 21725139
TI  - Monte Carlo simulation of electron beams generated by a 12 MeV dedicated mobile
      IORT accelerator.
AB  - The aim of this study was to investigate the dosimetric characteristics of the
      electron beams generated by the light intraoperative accelerator, Liac(r)
      (SORDINA, Italy), using Monte Carlo (MC) calculations. Moreover we investigated
      the possibility of characterizing the Liac(r) dosimetry with a minimal set of
      dosimetric data. In fact accelerator commissioning requires measurements of both
      percentage depth doses (PDDs) and off-axis profiles for all the possible
      combinations of energy, applicator diameter and bevelled angle. The Liac(r)
      geometry and water phantom were simulated in a typical measurement setup, using
      the MC code EGSnrc/BEAMnrc. A simulated annealing optimization algorithm was used
      in order to find the optimal non-monoenergetic spectrum of the initial electron
      beam that minimizes the differences between calculated and measured PDDs. We have
      concluded that, for each investigated nominal energy beam, only the PDDs of
      applicators with diameters of 30, 70 and 100 mm and the PDD without an applicator
      were needed to find the optimal spectra. Finally, the output factors of the
      entire set of applicator diameters/bevelled angles were calculated. The
      differences between calculated and experimental output factors were better than
      2%, with the exception of the smallest applicator which gave differences between
      3% and 4% for all energies. The code turned out to be useful for checking the
      experimental data from various Liac(r) beams and will be the basis for developing
      a tool based on MC simulation to support the medical physicist in the
      commissioning phase.

PMID- 21725141
TI  - A comparison of MR-based attenuation correction in PET versus SPECT.
AB  - Attenuation correction (AC) is a critical step in the reconstruction of
      quantitatively accurate positron emission tomography (PET) and single photon
      emission computed tomography (SPECT) images. Several groups have proposed
      magnetic resonance (MR)-based AC algorithms for application in hybrid PET/MR
      systems. However, none of these approaches have been tested on SPECT data. Since
      SPECT/MR systems are under active development, it is important to ascertain
      whether MR-based AC algorithms validated for PET can be applied to SPECT. To
      investigate this issue, two imaging experiments were performed: one with an
      anthropomorphic chest phantom and one with two groups of canines. Both groups of
      canines were imaged from neck to abdomen, one with PET/CT and MR (n = 4) and the
      other with SPECT/CT and MR (n = 4), while the phantom was imaged with all
      modalities. The quality of the nuclear medicine reconstructions using MR-based
      attenuation maps was compared between PET and SPECT on global and local scales.
      In addition, the sensitivity of these reconstructions to variations in the
      attenuation map was ascertained. On both scales, it was found that the SPECT
      reconstructions were of higher fidelity than the PET reconstructions. Further,
      they were less sensitive to changes to the MR-based attenuation map. Thus, MR
      based AC algorithms that have been designed for PET/MR can be expected to
      demonstrate improved performance when used for SPECT/MR.

PMID- 21725142
TI  - Spherical polar co-ordinate calculations of induced fields in the retina and head
      for applied magnetic fields at 50 Hz.
AB  - This paper sets out to explore the effects of voxel resolution, from 2 mm down to
      0.1 mm for Cartesian co-ordinates and the differences between Cartesian and
      spherical polar co-ordinates for a standardized test-bed model of the eye. This
      model was taken from the work of Yoriyaz et al (2005 Radiat. Prot. Dosim. 115 316
      9) who have developed a detailed geometric description of the eye including
      choroid, retina, sclera, lens, cornea, anterior chamber, vitreous humour and
      optic nerve for ophthalmic brachytherapy. The spherical co-ordinate model has
      radial and angular steplengths of 0.1 mm and 0.25 degrees , respectively. The
      current density averaged over 1 cm(2) and the 99th percentile value of the
      induced electric field have been calculated in the retina and central nervous
      system for uniform magnetic fields. The Cartesian co-ordinate calculations
      proceed in a sequence of grids at 2, 1, 0.5, 0.2 and 0.1 mm resolution with the
      potentials from the previous calculation at a coarser grid providing the boundary
      conditions on the finer grid. The 0.2 mm grid provides the boundary conditions
      for the spherical polar calculations. Comparisons are made with the International
      Commission on Non-Ionizing Radiation Protection reference levels.

PMID- 21725140
TI  - Comparison of manual and automatic segmentation methods for brain structures in
      the presence of space-occupying lesions: a multi-expert study.
AB  - The purpose of this work was to characterize expert variation in segmentation of
      intracranial structures pertinent to radiation therapy, and to assess a
      registration-driven atlas-based segmentation algorithm in that context. Eight
      experts were recruited to segment the brainstem, optic chiasm, optic nerves, and
      eyes, of 20 patients who underwent therapy for large space-occupying tumors.
      Performance variability was assessed through three geometric measures: volume,
      Dice similarity coefficient, and Euclidean distance. In addition, two simulated
      ground truth segmentations were calculated via the simultaneous truth and
      performance level estimation algorithm and a novel application of probability
      maps. The experts and automatic system were found to generate structures of
      similar volume, though the experts exhibited higher variation with respect to
      tubular structures. No difference was found between the mean Dice similarity
      coefficient (DSC) of the automatic and expert delineations as a group at a 5%
      significance level over all cases and organs. The larger structures of the
      brainstem and eyes exhibited mean DSC of approximately 0.8-0.9, whereas the
      tubular chiasm and nerves were lower, approximately 0.4-0.5. Similarly low DSCs
      have been reported previously without the context of several experts and patient
      volumes. This study, however, provides evidence that experts are similarly
      challenged. The average maximum distances (maximum inside, maximum outside) from
      a simulated ground truth ranged from (-4.3, +5.4) mm for the automatic system to
      (-3.9, +7.5) mm for the experts considered as a group. Over all the structures in
      a rank of true positive rates at a 2 mm threshold from the simulated ground
      truth, the automatic system ranked second of the nine raters. This work
      underscores the need for large scale studies utilizing statistically robust
      numbers of patients and experts in evaluating quality of automatic algorithms.

PMID- 21725143
TI  - Dual-isotope PET using positron-gamma emitters.
AB  - Positron emission tomography (PET) is widely recognized as a highly effective
      functional imaging modality. Unfortunately, standard PET cannot be used for dual
      isotope imaging (which would allow for simultaneous investigation of two
      different biological processes), because positron-electron annihilation products
      from different tracers are indistinguishable in terms of energy. Methods that
      have been proposed for dual-isotope PET rely on differences in half-lives of the
      participating isotopes; these approaches, however, require making assumptions
      concerning kinetic behavior of the tracers and may not lead to optimal results.
      In this paper we propose a novel approach for dual-isotope PET and investigate
      its performance using GATE simulations. Our method requires one of the two
      radioactive isotopes to be a pure positron emitter and the second isotope to emit
      an additional high-energy gamma in a cascade simultaneously with positron
      emission. Detection of this auxiliary prompt gamma in coincidence with the
      annihilation event allows us to identify the corresponding 511 keV photon pair as
      originating from the same isotope. Two list-mode datasets are created: a primary
      dataset that contains all detected 511 keV photon pairs from both isotopes, and a
      second, tagged (much smaller) dataset that contains only those PET events for
      which a coincident prompt gamma has also been detected. An image reconstructed
      from the tagged dataset reflects the distribution of the second positron-gamma
      radiotracer and serves as a prior for the reconstruction of the primary dataset.
      Our preliminary simulation study with partially overlapping (18)F/(22)Na and
      (18)F/(60)Cu radiotracer distributions showed that in these two cases the dual
      isotope PET method allowed for separation of the two activity distributions and
      recovered total activities with relative errors of about 5%.

PMID- 21725144
TI  - Breath acetone concentration; biological variability and the influence of diet.
AB  - Previous measurements of acetone concentrations in the exhaled breath of healthy
      individuals and the small amount of comparable data for individuals suffering
      from diabetes are briefly reviewed as a prelude to the presentation of new data
      on the sporadic and wide variations of breath acetone that occur in ostensibly
      healthy individuals. Data are also presented which show that following a
      ketogenic diet taken by eight healthy individuals their breath acetone
      concentrations increased up to five times over the subsequent 6 h. Similarly, the
      breath acetone increased six and nine times when a low carbohydrate diet was
      taken by two volunteers and remained high for the several days for which the diet
      was continued. These new data, together with the previous data, clearly indicate
      that diet and natural intra-individual biological and diurnal variability result
      in wide variations in breath acetone concentration. This places an uncertainty in
      the use of breath acetone alone to monitor blood glucose and glycaemic control,
      except and unless the individual acts as their own control and is cognizant of
      the need for dietary control.

PMID- 21725145
TI  - Can baroreflex measurements with spontaneous sequence analysis be improved by
      also measuring breathing and by standardization of filtering strategies?
AB  - Baroreflex sensitivity (BRS) is known to be attenuated by inspiration and all the
      original BRS methodologies took this into account by measuring only in
      expiration. Spontaneous sequence analysis (SSA) is a non-invasive clinical tool
      widely used to estimate BRS in Man but does not take breathing into account. We
      have therefore modified it to test whether it too can detect inspiratory
      attenuation. Traditional SSA is also entangled with issues of distinguishing
      causal from random relationships between blood pressure and heart period and of
      the optimum choice of data filter settings. We have also tested whether the
      sequences our modified SSA rejects do behave as random relationships and show the
      limitations of the absence of filter standardization. SSA was performed on
      eupneic data from 1 h periods in 20 healthy subjects. Applying SSA traditionally
      produced a mean BRS of 23 +/- 3 ms mmHg(-1). After modification to measure
      breathing, SSA detected significant inspiratory attenuation (11 +/- 1 ms mmHg(
      1)), and the mean expiratory BRS was significantly higher (26 +/- 5 ms mmHg(-1)).
      Traditional SSA therefore underestimates BRS by an amount (3 ms mmHg(-1)) as big
      as the major physiological and clinical factors known to alter BRS. We show that
      the sequences rejected by SSA do behave like random associations between pressure
      and period. We also show the minimal effect of the r(2) filter and the biases
      that some pressure and heart period filters can introduce. We discuss whether SSA
      might be improved by standardization of filter settings and by also measuring
      breathing.

PMID- 21725146
TI  - Laser sintering fabrication of three-dimensional tissue engineering scaffolds
      with a flow channel network.
AB  - The fabrication of tissue engineering scaffolds for the reconstruction of highly
      oxygen-dependent inner organs is discussed. An additive manufacturing technology
      known as selective laser sintering was employed to fabricate a highly porous
      scaffold with an embedded flow channel network. A porogen leaching system was
      used to obtain high porosity. A prototype was developed using the biodegradable
      plastic polycaprolactone and sodium chloride as the porogen. A high porosity of
      90% was successfully obtained. Micro x-ray CT observation was carried out to
      confirm that channels with a diameter of approximately 1 mm were generated
      without clogging. The amount of residual salt was 930 ug while the overall volume
      of the scaffold was 13 cm(3), and it was confirmed that the toxicity of the salt
      was negligible. The hydrophilization of the scaffold to improve cell adhesion on
      the scaffold is also discussed. Oxygen plasma ashing and hydrolysis with sodium
      hydroxide, typically employed to improve the hydrophilicity of plastic surfaces,
      were tested. The improvement of hydrophilicity was confirmed by an increase in
      water retention by the porous scaffold from 180% to 500%.

PMID- 21725147
TI  - Development of a hybrid scaffold with synthetic biomaterials and hydrogel using
      solid freeform fabrication technology.
AB  - Natural biomaterials such as hyaluronic acid, gelatin and collagen provide
      excellent environments for tissue regeneration. Furthermore, gel-state natural
      biomaterials are advantageous for encapsulating cells and growth factors. In cell
      printing technology, hydrogel which contains cells was printed directly to form
      three-dimensional (3D) structures for tissue or organ regeneration using various
      types of printers. However, maintaining the 3D shape of the printed structure,
      which is made only of the hydrogel, is very difficult due to its weak mechanical
      properties. In this study, we developed a hybrid scaffold consisting of synthetic
      biomaterials and natural hydrogel using a multi-head deposition system, which is
      useful in solid freeform fabrication technology. The hydrogel was intentionally
      infused into the space between the lines of a synthetic biomaterial-based
      scaffold. The cellular efficacy of the hybrid scaffold was validated using rat
      primary hepatocytes and a mouse pre-osteoblast MC3T3-E1 cell line. In addition,
      the collagen hydrogel, which encapsulates cells, was dispensed and the viability
      of the cells observed. We demonstrated superior effects of the hybrid scaffold on
      cell adhesion and proliferation and showed the high viability of dispensed cells.

PMID- 21725148
TI  - Design and fabrication of a novel porous implant with pre-set channels based on
      ceramic stereolithography for vascular implantation.
AB  - Being a multi-etiological factors disease, osteonecrosis of the femoral head
      affects many young people, leading to the collapse of the femur head; eventually
      the hip arthroplasty is needed if not treated in time. Unfortunately, as yet, no
      satisfactory therapy to repair necrotic bone at an early stage is present. Novel
      implants with pre-set channels were designed for the treatment of early femoral
      head necrosis. Ceramic stereolithography was applied to fabricate the green part
      from beta-TCP powder. Other processes, such as dehydration, rinsing, drying and
      sintering, were processed successively. The final ceramic part remains the same
      as the engineered part in both shape and internal structure. No significant
      deformation or crack occurred. X-ray diffraction showed that no facies changed or
      chemical reaction occurred during the fabrication process. The chemical
      composition remains the same as that of the original beta-TCP powder. The
      compressive strength is 23.54 MPa, close to that of natural cancellous bone.
      Novel implants with a pre-set channel were designed and fabricated for blood
      vessel implantation. Bioceramic stereolithography technology based directly on
      the CAD model in this research shows advantages in accurate design, optimization
      of 3D scaffold and critical control of the fabrication process. This proposed
      implant shows promising clinical application in the restoration of early femoral
      head necrosis.

PMID- 21725149
TI  - Laser-guidance-based cell deposition microscope for heterotypic single-cell
      micropatterning.
AB  - Cell patterning methods enable researchers to control specific homotypic and
      heterotypic contact-mediated cell-cell and cell-ECM interactions and to impose
      defined cell and tissue geometries. To micropattern individual cells to specific
      points on a substrate with high spatial resolution, we have developed a cell
      deposition microscope based on the laser-guidance technique. We discuss the
      theory of optical forces for generating laser guidance and the optimization of
      the optical configuration (NA ~ 0.1) to manipulate cells with high speed in three
      dimensions. Our cell deposition microscope is capable of patterning different
      cell types onto and within standard cell research devices and providing on-stage
      incubation for long-term cell culturing. Using this cell deposition microscope,
      rat mesenchymal stem cells from bone marrow were micropatterned with
      cardiomyocytes into a substrate microfabricated with polydimethylsiloxane on a 22
      mm * 22 mm coverglass to form a single-cell coculturing microenvironment, and
      their electrophysiological property changes were investigated during the
      coculturing days.

PMID- 21725150
TI  - A functionally gradient variational porosity architecture for hollowed scaffolds
      fabrication.
AB  - This paper presents a novel continuous tool-path planning methodology for
      hollowed scaffold fabrication in tissue engineering. A new functionally gradient
      porous architecture is proposed with a continuous material deposition planning
      scheme. A controllable variational pore size and hence the porosity have been
      achieved with a combination of two geometrically oriented consecutive layers. The
      desired porosity has been achieved with consecutive layers by geometrically
      partitioning each layer into sub-regions based on the area and the tissue
      scaffold design constraints. A continuous, interconnected and optimized tool-path
      for layers has been generated for a three-dimensional biomaterial
      deposition/printing process. A zigzag pattern tool-path has been proposed for an
      accumulated sub-region layer, and a concentric spiral-like optimal tool-path
      pattern has been generated for the successive layer to ensure continuity along
      the structure. Three-dimensional layers, formed by the proposed tool-path plan,
      vary the pore size and the porosity based on the biological and mechanical
      requirements. Several examples demonstrate the proposed methodology along with
      illustrative results. Also a comparative study between the proposed design and
      conventional Cartesian coordinate scaffolds has been performed. The results
      demonstrate a significant reduction in design error with the proposed method.
      Moreover, sample examples have been fabricated using a micro-nozzle biomaterial
      deposition system, and characterized for validation.

PMID- 21725151
TI  - Biofabrication of chitosan-silver composite SERS substrates enabling
      quantification of adenine by a spectroscopic shift.
AB  - Surface-enhanced Raman scattering (SERS) has grown dramatically as an analytical
      tool for the sensitive and selective detection of molecules adsorbed on nano
      roughened noble metal structures. Quantification with SERS based on signal
      intensity remains challenging due to the complicated fabrication process to
      obtain well-dispersed nanoparticles and well-ordered substrates. We report a new
      biofabrication strategy of SERS substrates that enable quantification through a
      newly discovered spectroscopic shift resulting from the chitosan-analyte
      interactions in solution. We demonstrate this phenomenon by the quantification of
      adenine, which is an essential part of the nucleic acid structure and a key
      component in pathways which generate signal molecules for bacterial
      communications. The SERS substrates were fabricated simply by sequential
      electrodeposition of chitosan on patterned gold electrodes and electroplating of
      a silver nitrate solution through the chitosan scaffold to form a chitosan-silver
      nanoparticle composite. Active SERS signals of adenine solutions were obtained in
      real time from the chitosan-silver composite substrates with a significant
      concentration-dependent spectroscopic shift. The Lorentzian curve fitting of the
      dominant peaks suggests the presence of two separate peaks with a concentration
      dependent area percentage of the separated peaks. The chitosan-mediated composite
      SERS substrates can be easily biofabricated on predefined electrodes within
      microfluidic channels for real-time detection in microsystems.

PMID- 21725153
TI  - Development of novel hybrid poly(L-lactide)/chitosan scaffolds using the rapid
      freeze prototyping technique.
AB  - Engineered scaffolds have been shown to be critical to various tissue engineering
      applications. This paper presents the development of a novel three-dimensional
      scaffold made from a mixture of chitosan microspheres (CMs) and poly(L-lactide)
      by means of the rapid freeze prototyping (RFP) technique. The CMs were used to
      encapsulate bovine serum albumin (BSA) and improve the scaffold mechanical
      properties. Experiments to examine the BSA release were carried out; the BSA
      release could be controlled by adjusting the crosslink degree of the CMs and
      prolonged after the CMs were embedded into the PLLA scaffolds, while the
      examination of the mechanical properties of the scaffolds illustrates that they
      depend on the ratio of CMs to PLLA in the scaffolds as well as the cryogenic
      temperature used in the RFP fabrication process. The chemical characteristics of
      the PLLA/chitosan scaffolds were evaluated by Fourier transform infrared (FTIR)
      spectroscopy. The morphological and pore structure of the scaffolds were also
      examined by scanning electron microscopy and micro-tomography. The results
      obtained show that the scaffolds have higher porosity and enhanced pore size
      distribution compared to those fabricated by the dispensing-based rapid
      prototyping technique. This study demonstrates that the novel scaffolds have not
      only enhanced porous structure and mechanical properties but also showed the
      potential to preserve the bioactivities of the biomolecules and to control the
      biomolecule distribution and release rate.

PMID- 21725154
TI  - High-resolution extracellular stimulation of dispersed hippocampal culture with
      high-density CMOS multielectrode array based on non-Faradaic electrodes.
AB  - We introduce a method to electrically stimulate individual neurons at single-cell
      resolution in arbitrary spatiotemporal patterns with precise control over
      stimulation thresholds. By exploiting a custom microelectronic chip, up to 65,000
      non-Faradaic electrodes can be uniquely addressed with electrode density
      exceeding 6500 electrodes mm(-2). We demonstrate extracellular stimulation of
      dispersed primary hippocampal neuronal cultures using the chip at single-cell
      resolution.

PMID- 21725152
TI  - Microengineering methods for cell-based microarrays and high-throughput drug
      screening applications.
AB  - Screening for effective therapeutic agents from millions of drug candidates is
      costly, time consuming, and often faces concerns due to the extensive use of
      animals. To improve cost effectiveness, and to minimize animal testing in
      pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate
      assays have been developed. Integration of cell microarrays with microfluidic
      systems has facilitated automated and controlled component loading, significantly
      reducing the consumption of the candidate compounds and the target cells. Even
      though these methods significantly increased the throughput compared to
      conventional in vitro testing systems and in vivo animal models, the cost
      associated with these platforms remains prohibitively high. Besides, there is a
      need for three-dimensional (3D) cell-based drug-screening models which can mimic
      the in vivo microenvironment and the functionality of the native tissues. Here,
      we present the state-of-the-art microengineering approaches that can be used to
      develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell
      culture systems with live cell-based arrays, microfluidic cell culture systems,
      and their application to high-throughput drug screening. We conclude that among
      the emerging microengineering approaches, bioprinting holds great potential to
      provide repeatable 3D cell-based constructs with high temporal, spatial control
      and versatility.

PMID- 21725156
TI  - Detection of deafness-causing mutations in the Greek mitochondrial genome.
AB  - Mitochondrion harbors its own DNA, known as mtDNA, encoding certain essential
      components of the mitochondrial respiratory chain and protein synthesis
      apparatus. mtDNA mutations have an impact on cellular ATP production and many of
      them are undoubtedly a factor that contributes to sensorineural deafness,
      including both syndromic and non-syndromic forms. Hot spot regions for deafness
      mutations are the MTRNR1 gene, encoding the 12S rRNA, the MTTS1 gene, encoding
      the tRNA for Ser<formula>^{(UCN)}</formula>, and the MTTL1 gene, encoding the
      tRNA for Leu<formula>^{(UUR)}</formula>. We investigated the impact of mtDNA
      mutations in the Greek hearing impaired population, by testing a cohort of 513
      patients suffering from childhood onset prelingual or postlingual, bilateral,
      sensorineural, syndromic or non-syndromic hearing loss of any degree for six
      mitochondrial variants previously associated with deafness. Screening involved
      the MTRNR1 961delT/insC and A1555G mutations, the MTTL1 A3243G mutation, and the
      MTTS1 A7445G, 7472insC and T7510C mutations. Although two patients were tested
      positive for the A1555G mutation, we failed to identify any subject carrying the
      961delT/insC, A3243G, A7445G, 7472insC, or T7510C mutations. Our findings
      strongly support our previously raised conclusion that mtDNA mutations are not a
      major risk factor for sensorineural deafness in the Greek population.

PMID- 21725155
TI  - Deregulated expression of superoxide dismutase-2 correlates with different stages
      of cervical neoplasia.
AB  - OBJECTIVE: Superoxide dismutase-2 (SOD2) is considered one of the most important
      antioxidant enzymes that regulate cellular redox state in normal and tumorigenic
      cells. Overexpression of this enzyme may be involved in carcinogenesis,
      particularly in lung, gastric, colorectal and breast cancer. METHODS: In the
      present study, we have evaluated SOD2 protein levels by immunohistochemistry
      (IHC) in 331 cervical histological samples including 31 low-grade cervical
      intraepithelial neoplasia (LSIL), 51 high-grade cervical intraepithelial
      neoplasia (HSIL), 197 squamous cervical carcinomas (SCC) and 52 cervical
      adenocarcinomas (ADENO). RESULTS: We observed that SOD2 staining increases with
      cervical disease severity. Intense SOD2 staining was found in 13% of LSIL, 25.5%
      of HSIL and 40% of SCC. Moreover, 65.4% of ADENO exhibited intense SOD2 staining.
      CONCLUSIONS: Differences in the expression of SOD2 could potentially be used as a
      biomarker for the characterization of different stages of cervical disease.

PMID- 21725157
TI  - Effects of six functional SNPs on the urinary 8-isoprostane level in a general
      Japanese population; Shimane COHRE Study.
AB  - Oxidative stress is an important risk factor for cardiovascular diseases.
      Although a variety of genetic factors are assumed to contribute to the regulation
      of oxidative stress, evidence in human populations is insufficient. In this
      study, we therefore evaluated the effects of six functional single-nucleotide
      polymorphisms (SNPs) on the oxidative stress under a cross-sectional study
      design. Participants of the health examination in two neighboring counties were
      recruited in a mountainous region of Shimane prefeture, Japan (n=1092). As a
      marker for the oxidative stress, the urinary 8-isoprostane (IsoP) was measured by
      ELISA. The six SNPs were genotyped using the Taqman method. None of the SNPs
      showed a significant effect on the IsoP level. However, the Generalized Multiple
      Dimensionality Reduction (GMDR) method identified that the combination of the two
      SNPs, MTHFR C677T and eNOS T-786C, showed a significant effect on the IsoP level
      in this population. The linear regression analysis confirmed that the high risk
      genotype identified in the GMDR was an independent factor influencing the IsoP
      even after adjustment of confounding factors. This result suggested that GMDR
      analysis might be useful to identify concealed effects of combined SNPs.

PMID- 21725158
TI  - Use of host- and bacteria-derived salivary markers in detection of periodontitis:
      a cumulative approach.
AB  - In the present study, we propose a novel diagnostic approach, using 3 different
      salivary markers, representing periodontal pathogen burden, inflammation, and
      tissue degradation, for detecting periodontitis. The salivary concentrations of
      Porphyromonas gingivalis, interleukin-1beta, and matrix metalloproteinase-8,
      available from salivary specimens of 165 subjects (84 subjects with advanced
      periodontitis and 81 controls), were calculated together to obtain a cumulative
      risk score (CRS). In the calculation of CRS, the concentrations of each marker
      were divided into tertiles, and cumulative sub-score per each subject were
      calculated by the multiplication of the tertile values. Three CRS groups,
      indicating the lowest, medium, or highest risk, were formed with the cumulative
      sub-scores. Logistic regression analysis and ROC curves were performed to study
      the association of CRS with periodontitis. The results indicate that CRS,
      calculated from the 3 salivary biomarkers, is associated with advanced
      periodontitis more strongly than any of the markers individually. CRS offers a
      novel, non-invasive model for advanced periodontitis risk categorization that is
      especially useful in large population surveys where a periodontal examination is
      not feasible.

PMID- 21725159
TI  - Clinical utility of alpha fetoprotein and HCCR-1, alone or in combination, in
      patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
AB  - Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting
      patients with hepatocellular carcinoma (HCC). However, it has been indicated that
      HCCR-1 (human cervical cancer oncogene 1) might be supplementary to AFP in the
      detection. We conducted a prospective study in 120 normal and 524 liver disease
      patients to evaluate the significance of simultaneous measurement of 2 tumor
      markers (AFP and HCCR-1) in the diagnosis of HCC through the cohort study in
      Korea and China. We also performed immunohistochemical studies using 25 normal
      subjects (N), 32 liver cirrhosis (LC) and 116 HCC tissues. The sensitivities of
      AFP (20 ng/mL) and HCCR-1 (10 ng/mL) in HCC were 55.8% (164/294) and 44.2%
      (130/294), respectively. When AFP was combined with HCCR-1, sensitivities
      increased to 4.2% (N), 12.7% (chronic hepatitis; CH), 50.0% (LC), and 77.2%
      (HCC), respectively. Although there was no significant difference in the
      diagnostic rate for HCC between AFP and HCCR-1, many cases for AFP-negative HCC
      were positive for HCCR-1 and vice versa. Moreover, the combined use of AFP and
      HCCR-1 improved the diagnostic rate to 70.8% in small HCC (< 2 cm) and 81.6% in
      large HCC (? 2 cm), respectively. AFP and HCCR-1 are independent markers. Our
      result suggests that the HCCR-1 could be an useful biomarker for HCC while the
      diagnostic rate could be significantly improved in the combined use of HCCR-1 and
      AFP.

PMID- 21725160
TI  - Glycated lysine residues: a marker for non-enzymatic protein glycation in age
      related diseases.
AB  - Nonenzymatic glycosylation or glycation of macromolecules, especially proteins
      leading to their oxidation, play an important role in diseases. Glycation of
      proteins primarily results in the formation of an early stage and stable Amadori
      lysine product which undergo further irreversible chemical reactions to form
      advanced glycation endproducts (AGEs). This review focuses these products in
      lysine rich proteins such as collagen and human serum albumin for their role in
      aging and age-related diseases. Antigenic characteristics of glycated lysine
      residues in proteins together with the presence of serum autoantibodies to the
      glycated lysine products and lysine-rich proteins in diabetes and arthritis
      patients indicates that these modified lysine residues may be a novel biomarker
      for protein glycation in aging and age-related diseases.

PMID- 21725161
TI  - Crosstalk between activated and inactivated c-Src in hepatocellular carcinoma.
AB  - C-Src activity is regulated by tyrosine phosphorylation at two distinct sites,
      Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these
      sites in human cancers are not well defined. This study aims to determine whether
      the alterations and crosstalk of these two sites may contribute to hepatocellular
      carcinoma (HCC). Specimens from 85 patients who had undergone curative
      hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p
      Tyr527-Src, as well as the non-phosphorylated status for each site, were
      determined using immunohistochemistry and statistically correlated with
      clinicopathological characteristics and overall survival rate. The active state
      of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade (P=0.062)
      but inversely correlated with vascular invasion (P=0.071). Its non-phosphorylated
      status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade
      (P= 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased
      in male patients but increased HCV-infected patients (P=0.044 and 0.033). The
      Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and
      decreased non-p-Tyr527-c-Src expression were associated with a poor patient
      survival rate (P=0.004 and 0.025). Interestingly, the expression of non-p-Tyr416
      c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions
      (P=0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and
      non-p-Tyr527-c-Src expression had a prolonged overall survival rate (P=0.030). A
      multivariable COX regression model showed that p-Tyr416-c-Src expression was an
      effective predictor for patient survival in HCC [OR =3.78, 95% CI =1.46-9.76;
      P=0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may
      serve as an independent prognostic marker of patient survival in HCC. Relative
      levels of other phosphorylated or non-phosphorylated c-Src kinases may also
      present different statuses during HCC development and require further
      investigation.

PMID- 21725162
TI  - Gender differences in the prodromal signs of dementia: memory complaint and IADL
      restriction. a prospective population-based cohort.
AB  - Subjective memory complaint (SMC) and restriction in cognitively-complex
      activities of daily living (such as instrumental ADL) are two early symptoms
      observed in the prodromal phase of dementia and may represent useful alarm
      signals for general practitioners for an increased risk of subsequent dementia.
      We here studied in a large population-based epidemiological cohort on aging, the
      risk of dementia associated with SMC and restriction in IADL, with a specific
      interest in a potential interaction by gender. The sample included 2,901
      subjects, aged 65 years and over, initially free of dementia and followed over 15
      years. After controlling for education, marital status, depressive
      symptomatology, and global cognition (MMSE), IADL-restriction was associated with
      an increased risk of dementia only in men (HR = 2.04, 1.27 to 3.29), whereas SMC
      was not (p = 0.95). The reverse was observed in females, in whom SMC almost
      doubled the risk of dementia (1.48 to 2.41), with no association with IADL
      restriction (p = 0.74). Finally, we distinguished the risk of dementia at short
      term (in the first 5 years), mid-term (between 5 and 10 years), and long-term
      (between 10 and 15 years). In women, SMC was significantly associated with
      greater risk of dementia whatever the risk period considered, even at longer term
      (HR = 1.61, p = 0.0216), whereas in men the increased risk was also observed with
      IADL-restriction and only in the first 5 years. To conclude, women would report
      the first symptoms very early in the process by SMC, whereas men would tend to
      later report their difficulties and only in terms of IADL-restriction.

PMID- 21725164
TI  - Assessment and treatment of common persistent sequelae following blast induced
      mild traumatic brain injury.
AB  - The ongoing wars in Iraq and Afghanistan and terrorist activity worldwide have
      been associated with an increased incidence of blast injuries. While blast
      injuries share similarities with blunt or penetrating traumatic injuries, there
      are unique mechanistic elements of blast injury that create increased
      vulnerability to damage of specific organs. This review highlights the mechanism
      of blast-related injury, describes the common sequelae of blast exposure that may
      impact rehabilitation care, and summarizes the intervention strategies for these
      blast-related sequelae.

PMID- 21725165
TI  - Parental stress and marital relationships among patients with brain injury and
      their spouses.
AB  - INTRODUCTION/OBJECTIVES: This study examines parental stress and marital
      relationship among patients with acquired brain injury and their spouses.
      PARTICIPANTS, MATERIALS/METHODS: The participants were 35 patients diagnosed with
      acquired brain injury and having school-aged children, together with their
      spouses recruited from out-patients from brain injury rehabilitation units across
      Denmark. The parents self-reported parental stress using the Parental Stress
      Index (PSI), marital adjustment using the Dyadic Adjustment Scale (DAS), family
      functioning using the Family Environment Scale (FES). Additionally, the healthy
      parents completed the Symptom Checklist 90 (SCL-90) measuring psychological
      symptoms. A matched control group consisted of parents suffering from diabetes
      and their spouses, being recruited from the National Danish Diabetes Register.
      RESULTS: Significantly more symptoms of parental stress were reported by the
      brain-injured parents when compared to the diabetic parents (p < 0.05); the brain
      injured parents also reported significant more family dysfunction (p < 0.05). The
      healthy parents in the brain injury group rated their marital satisfaction and
      current relationship happiness significantly lower (p < 0.05) than the healthy
      control group. The spouses to the brain-injured patients were also significantly
      more depressed (p < 0.01). CONCLUSIONS: When parents have acquired brain injury,
      they experience more parental stress and family dysfunction. Their spouses are
      less satisfied in their marital relationship and feel more depressed. These
      results indicate the need of a family centred supportive service to focus on the
      relational changes and dysfunctional family processes in families with a brain
      injured parent and dependent children.

PMID- 21725166
TI  - Altered cortical somatosensory processing in chronic stroke: A relationship with
      post-stroke shoulder pain.
AB  - Post-stroke shoulder pain (PSSP), traditionally regarded as purely nociceptive
      pain, is often persistent and the mechanisms underlying the pain complaints are
      not well understood. This explorative study is the first to address the possible
      changes in cortical somatosensory processing in patients with PSSP. Cortical
      potentials were recorded following intracutaneous electrostimulaton in stroke
      patients with chronic PSSP (n= 6), pain-free stroke patients (PF, n=14) and
      healthy controls (HC, n=20) using EEG. Amplitudes and latencies of both sensory
      discriminative (N90) as well as cognitive evaluative (N150, P200, the N150-P200
      peak-to-peak difference and P300) evoked potential components were evaluated.
      Stroke was associated with reduced N150 and P300 amplitudes and increased N90,
      N150 and P300 latencies at both sides. Compared to PF and HC, the P200 and N150
      P200 latencies were increased in PSSP patients after stimulation at both sides,
      even when comparing subgroups with similar lesion size and location. Stroke was
      associated with reduced sensory-discriminative as well as with reduced cognitive
      evaluative cortical somatosensory processing. This reduction was more pronounced
      in patients with PSSP and may be related to the central effects of persistent
      nociceptive pain.

PMID- 21725167
TI  - A review of diffusion tensor imaging studies on motor recovery mechanisms in
      stroke patients.
AB  - For the past decade, diffusion tensor imaging (DTI) has been used in elucidation
      of the motor recovery mechanisms in stroke patients. In the current study, I
      reviewed the DTI studies with regard to the motor recovery mechanisms in stroke
      patients, according to the following classification of motor recovery mechanisms;
      recovery of a damaged lateral corticospinal tract (CST), subcortical peri
      lesional reorganization, ipsilateral motor pathway from the unaffected motor
      cortex to the affected extremities, and other motor recovery mechanisms. In
      addition, I discussed the characteristics of DTI as an evaluation tool for motor
      recovery mechanisms and future direction. DTI has a unique advantage in
      identification and estimation of neural tracts at the subcortical level.
      Therefore, it could contribute much to research on the motor recovery mechanisms
      of stroke patients, especially, in terms of recovery of a damaged CST and
      subcortical peri-lesional reorganization. In spite of the advantages of DTI,
      fewer DTI studies on this topic have been conducted compared to studies using
      transcranial magnetic stimulation or functional MRI. Therefore, the total number
      of DTI studies on this topic should be increased. Moreover, further studies on
      various topics related to brain plasticity of motor function, as well as the
      motor recovery mechanism itself, should be encouraged; for example, DTI changes
      with passage of time, with rehabilitative intervention, or with motor recovery.

PMID- 21725168
TI  - Stochastic resonance therapy in Parkinson's disease.
AB  - OBJECTIVE: To test the effects of stochastic whole body vibration (WBV) we
      performed a double-blind randomized controlled study. METHODS: Patients were
      allocated either to the experimental or sham group. The experimental group
      received 5 cycles of stochastic WBV on three days, each cycle consisting of 5
      stimulus trains of 60 seconds duration (frequency 6.5 Hz) and 60 seconds resting
      time between stimuli. Patients allocated to the control group received a sham
      treatment with 1 Hz. Unified Parkinson's Disease Rating Scale, part III
      (UPDRSIII) was performed after treatment at baseline, after the first series on
      day 1 and on day 5. RESULTS: The reduction of subscores included in UPDRS III
      relative to baseline served as primary outcome measure. After the five-day course
      bradykinesia was improved in 14 of 18 patients (77.8%) and postural stability in
      8 of 18 (44.4%). Speech and facial expression remained unchanged in both groups.
      Tremor (p=0.027) and postural stability (p=0.048) showed a reduction also, but
      did not reached level of significance (p < 0.01); UPDRSIII sum score was improved
      by 26.7%. CONCLUSION: Stochastic whole body vibration may offer a supplementation
      to canonical physical treatments of PD motor symptoms.

PMID- 21725169
TI  - Effect of endurance exercise training on the expression of GFAP, S100B, and NSE
      in the striatum of chronic/progressive mouse model of Parkinson's disease.
AB  - GOALS AND OBJECTIVES: Parkinson's disease (PD) is one of the most common
      neurodegenerative diseases in elderly. Glial fibrillary acidic protein (GFAP),
      calcium-binding protein (S100B), and neuron-specific enolase (NSE) are brain
      damage markers. The main goal of this study is to investigate the expression of
      these markers in the striatum (ST) of chronic/progressive mouse model of PD, and
      to study the effect of endurance exercise training on the expression of those
      markers. MATERIALS AND METHODS: In this study, forty C57BL/6 albino mice were
      randomly divided into four groups. Sedentary control (SC, n=10), exercise control
      (ExC, n=10), sedentary Parkinson's (SPD, n=10), and exercised Parkinson's (ExPD,
      n=10). Chronic Parkinsonism was induced by injecting the animals with 10 doses of
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) and probenecid (250
      mg/kg) over 5 weeks. Modified human treadmill was used to train the mice at a
      speed of 18 m/min, 0 degrees of inclination, 40 min/day, 5 days/week for 4 weeks.
      At the end of exercise training, we examined the expression of these markers on
      the striatum of the four animal groups using immunohistochemistry. RESULTS AND
      DISCUSSION: Parkinsonism increases the expression of NSE, S100B, and GFAP in the
      ST, p value P < 0.001, < 0.05, and < 0.7 respectively compared with control
      group. Exercise training decreases the expression of NSE, S100B, and GFAP in the
      exercised PD mice compared with sedentary PD mice p value < 0.005, < 0.02, and <
      0.40 respectively. CONCLUSION: Treadmill exercise training decreased the
      expression of brain damage markers in the striatum of chronic Parkinsonian mice,
      which can partially explain the beneficial neuroprotective role of exercise in
      patients with PD.

PMID- 21725170
TI  - Effect of kinesio taping on standing balance in subjects with multiple sclerosis:
      A pilot study?m{1}.
AB  - OBJECTIVE: The aim of this study was to assess the effect of Kinesio Taping on
      body stability in subjects with MS. STUDY DESIGN: Non controlled intervention
      study in a Rehabilitation Unit. INTERVENTION: A consecutive convenience sample of
      15 individuals with multiple sclerosis was assessed. Kinesio Tex Tape was applied
      directly to the skin of both calves and kept for the next two days. MAIN OUTCOME
      MEASURES: Clinical and stabilometric assessments were performed at baseline,
      immediately after application of the tape and the day after its removal. To
      control for learning effect 10 subject with multiple sclerosis were tested
      repeatedly under the same conditions without tape. RESULTS: No statistically or
      clinically relevant differences were observed among conditions in the
      mediolateral plane. In the AP plane Friedman's ANOVA showed statistically
      significant differences between baseline and taping condition with respect to
      length of sway. A trend towards statistically relevant differences were found
      also with respect to mean sway and velocity of sway. No learning effect was found
      for repeated testing within the no treated group. CONCLUSIONS: These preliminary
      results suggest that the use of ankle taping may be useful in immediately
      stabilising body posture.

PMID- 21725171
TI  - Improvement in strength following resistance training in MS patients despite
      varied disability levels.
AB  - Strength and endurance data from 67 participants with multiple sclerosis (MS)
      were compared before, during and after a 6-month program of standardized
      resistance training. The hypothesis was that a standardized, structured
      resistance training exercise program improves strength in MS patients with
      different levels of disability. The range of EDSS scores was 1-8: (40% - EDSS of
      1-4.5), (35% - EDSS of 5-7) (25% - EDSS of 7.5 or higher). This unique study
      evaluated patients with differing levels of disability for a change in strength
      and endurance following a 6-month training program. Data were analyzed by repeat
      measures and analysis of variables using Proc GLM in SAS to account for
      variability between subjects, and within subjects, due to repeated measures at 3
      time points. Each treatment was blocked by disability class. Every within
      treatment analysis was significant. Each exercise showed significant improvement
      in strength for participants, despite disability levels. Increases in strength
      followed parallel improvement pathways, at all disability levels. All but one
      treatment displayed highly significant improvement (p-value < 0.0001). The
      results demonstrated that all individuals with MS, despite disability levels,
      show parallel improvement in strength and endurance. This study supports the use
      of exercise, including resistance programs, for all MS patients.

PMID- 21725172
TI  - Optic radiation injury following traumatic epidural hematoma: Diffusion tensor
      imaging study.
AB  - Little is known about optic radiation (OR) injury in patients with traumatic
      brain injury (TBI). We report on a patient who showed an OR injury on diffusion
      tensor imaging (DTI) following traumatic epidural hematoma (EDH). A 38 year-old
      man with TBI and 7 age-matched normal subjects were enrolled in this study. The
      patient had fallen down stairs while in an alcohol intoxicated state. He
      underwent a craniotomy following diagnosis of traumatic EDH in the left temporo
      parietal lobe on brain CT. He complained of right bilateral homonymous
      hemianopsia, which was confirmed on the Humphrey visual field test. No lesion on
      the left OR was observed during brain MRI. We were not able to reconstruct the
      fiber tractography for the left OR in this patient. We found that the left OR had
      been injured most severely around the midportion between the lateral geniculate
      body and occipital pole. We determined that DTI would be a useful technique for
      detection of an OR injury in patients with TBI. Therefore, we believe that DTI
      should be performed along with conventional brain MRI for patients with visual
      field defects following TBI.

PMID- 21725173
TI  - Cardiovascular alterations heralded by intrathecal baclofen bolus.
AB  - We describe two patients in whom serious bradycardia and arterial hypotension
      occurred after a small intrathecal baclofen (ITB) test bolus. Both patients
      suffered from severe spasticity (one due to brain injury, one due to spinal cord
      injury). Medical history and diagnostic examinations revealed no previous
      cardiological problems. Ten minutes following a 50 MUg ITB bolus, patient 1
      developed bradycardia (58 bpm) and incomplete right branch block, lasting for 3
      hours. In patient 2, a 20 MUg ITB bolus was followed after 5 minutes by severe
      bradycardia (30 bpm) and hypotension (60/30 mmHg), without loss of consciousness,
      lasting for 10 minutes. Exaggerated muscle tone was alleviated in both patients
      after 2 hours by the applied doses. Neither patient underwent implantation of a
      permanent pump system, both were continued on oral baclofen. Despite numerous
      unremarkable repeat cardiological exams, both patients suffered fatal cardiac
      arrest one and two months later, respectively. Our observations suggest that ITB
      may herald cardiovascular dysfunction in predisposed patients. Careful
      cardiological examination before ITB treatment, and close monitoring during ITB
      testing in particular, is advised.

PMID- 21725174
TI  - Botulinum Toxin in the management of hitchhiker's toe.
AB  - INTRODUCTION: Hyperextension of the extensor hallucis longus (EHL) muscle is a
      well recognised disabling sequel of either pyramidal or extrapyramidal lesions
      causing what is known as striated or hitchhiker's toe. Surgery was the only
      effective strategy to manage EHL hyperextension before botulinum toxin's use to
      manage muscular dystonia and spasticity became widely popular. METHODS: A
      multicentre retrospective study. A standard proforma was sent to specialists in
      neurological rehabilitation dealing routinely with this problem. The data was
      analysed using descriptive statistics. RESULTS: Four consultants and two trainees
      representing five separate neurological rehabilitation services agreed to
      participate in the study. Full data was available from the 29 proformas
      completed. The subjects were 15 females with an age range between 20 and 78 years
      (mean 58.7). Stroke was the primary diagnosis in 18 subjects. Four subjects had
      bilateral involvement. 16 subjects had either an associated foot drop or equino
      varus deformity. Dysport(r) was used in 15 subjects with an average dose of 170
      units per injection and Botox(r) in the other 14 with an average dose of 65
      units. The treatment was effective in 24 subjects (83%). All patients receiving
      Dysport(r) responded to the treatment. Whilst 5 Botox(r) treated patients failed
      to respond to it (35% failure rate). Most of the non respondents seemed to
      receive insufficient doses of Botox(r) (below 60 units). Surgical management was
      successful in 3 out of the 5 non respondent cases. CONCLUSION: Botilinum Toxin is
      an effective and safe method to manage hitchhicker's toe. In our study the
      conversion ratio between Dysport(r) and Botox(r) was 2.5:1. Third of the patients
      receiving Botox(r) failed to respond to the treatment most probably due to
      insufficient doses used.

PMID- 21725175
TI  - Virtual realities as motivational tools for robotic assisted gait training in
      children: A surface electromyography study.
AB  - Patient's active cooperation is essential to achieve good outcome in pediatric
      rehabilitation. Therefore, virtual environments were developed to enhance robotic
      assisted gait training. The purpose of this study was to evaluate virtual
      realities as motivational tools during robotic assisted gait training with
      children in the pediatric Lokomat(r). Nine children with different gait disorders
      and eight healthy children participated in the study. Muscular effort of the
      lower leg was assessed by surface electromyography during a randomly designed
      training protocol with virtual realities. Self reported motivation was
      investigated with two questionnaires. Comparisons were drawn through repeated
      measurement Analysis of Variance and paired-t-tests. The logarithmic transformed
      data showed that the electromyographic activity output in both groups was
      significantly higher during tasks with virtual realities than during normal
      walking conditions. These results support that virtual realities seem to be
      efficient motivational tools to increase children's muscular effort in the
      pediatric Lokomat(r). The gaming aspect of virtual realities keeps children
      highly engaged during repetitive tasks.

PMID- 21725176
TI  - Update on diagnosis and treatment of resistant hypertension.
AB  - Resistant hypertension is an increasingly common medical problem, and patients
      with this condition are at a high risk of cardiovascular events. The prevalence
      of resistant hypertension is unknown, but data from clinical trials suggest that
      20% to 30% of hypertensive individuals may be resistant to antihypertensive
      treatment. The evaluation of these patients is focused on identifying true
      resistant hypertension and contributing and secondary causes of hypertension,
      including hyperaldosteronism, obstructive sleep apnea, chronic kidney disease,
      renal artery stenosis, and pheochromocytoma. Treatment includes removal of
      contributing factors, appropriate management of secondary causes, and use of
      effective multidrug regimens. More established approaches, such as low dietary
      salt and mineralocorticoid receptor blockers, and new technologies, such as
      carotid stimulation and renal denervation, have been used in the management of
      patients with resistant hypertension.

PMID- 21725177
TI  - Half-and-half nails.

PMID- 21725178
TI  - Blood pressure screening in school-aged children in Tehran.
AB  - INTRODUCTION: Hypertension is one of the most common diseases in the world and a
      major risk factor for cardiovascular, renal, and neurologic diseases. It seems
      that hypertension and overweight in children are a growing epidemic. The aim of
      this study was to investigate the prevalence of hypertension in school-aged
      children in Tehran. MATERIALS AND METHODS: In a cross-sectional study, blood
      pressure and anthropometric measurements were performed on school-aged children
      in Tehran from 2008 to 2009. Children aged 7 to 11 years from 5 public schools in
      Tehran were included. Blood pressure, weight, and height measurement were
      performed at the school. At each screening, 3 seated blood pressure, weight, and
      height measurements were made and at least after 3 minutes of rest and choosing
      proper cuff, blood pressure was measured by a pediatric nephrologist and a
      pediatric assistant. RESULTS: A total of 425 school-aged children were included.
      Twenty-four percent of the primary school children had hypertension and 12% were
      shown to be overweight. Hypertension was more common in students of the north of
      Tehran in comparison to other geographic parts of Tehran. There was a significant
      difference in the prevalence of hypertension between girl students of north of
      Tehran and girls of the other parts of Tehran. CONCLUSIONS: We concluded that
      hypertension is a common problem in school-aged children. Our study re-emphasized
      the need for prevention and control of high blood pressure in children to manage
      the global diseases burden due to hypertension.

PMID- 21725179
TI  - Relationship between O serotype and virulent genes in Escherichia coli causing
      urinary tract infections.
AB  - INTRODUCTION: Escherichia coli are the most frequent pathogens in acute urinary
      infections. They are classified based on various types of O antigen. Escherichia
      coli strains that cause urinary tract infections possess several genes encoding
      urovirulent factors. To assay the relation of virulent factors of E coli in acute
      urinary infections, the serotypes and virulence factor genotypes were determined.
      MATERIALS AND METHODS: We studied 96 E coli isolates from children with acute
      urinary infections. Four urovirulence determinants were analyzed by DNA colony
      hybridization, including the genes for type 1 fimbriae (pil), P fimbriae (pap), S
      fimbriae (sfa), hemolysin (hly), and cytotoxic necrotizing factor 1 (cnf1). O
      serotypes were also determined. RESULTS: The most frequently found virulence
      factor-encoding gene in the E coli strains studied was the gene for type 1
      fimbriae (27.4%). The prevalence of pap, sfa, hly, and cnf1 were higher in
      serotypes causing pyelonephritis than cystitis. The most common type of O antigen
      was O1 (12.2%). There was a significant correlation between serotype and genotype
      in uropathogenic E coli. CONCLUSIONS: The high prevalence of O6 serotypes in
      children urinary tract infections and the high percentage of virulent genes in
      serotype O6 suggested a close relation between serotype and genotypes of
      uropathogen E coli.

PMID- 21725180
TI  - Ifosfamide nephropathy in patients with sarcoma.
AB  - INTRODUCTION: Ifosfamide is an alkylating agent, frequently used in the treatment
      of sarcoma. Major side effects of ifosfamide are classified as nephropathy,
      neuropathy, and hematologic complications. The aim of present study was to
      determine the frequency and severity of ifosfamide nephropathy in patients with
      various types of sarcoma. MATERIALS AND METHODS: Ninety patients (52 males and 38
      females) who had received ifosfamide chemotherapy for sarcoma were included in
      this study. Data on physical examination, laboratory studies, and estimation of
      glomerular filtration rate were collected. The median duration of follow-up was 6
      to 12 months. Records of documented nephropathy were identified in these
      patients. RESULTS: The age range of patients on ifosfamide was 5 to 59 years.
      Thirty-four of the patients were children and 56 were adults. The most common
      renal side effects were proteinuria (15.5%), glycosuria (7.8%), elevation of
      serum creatinine (2.2%), hematuria (14.4%), and combination of proteinuria and
      glycosuria (5.5%). None of the patients had gross hematuria, but microscopic
      hematuria was present in 14.4%. CONCLUSIONS: Ifosfamide nephropathy was seen with
      different degrees of severity in patients with sarcoma. Monitoring of the side
      effects of ifosfamide should be revised in different populations.

PMID- 21725181
TI  - Prognostic value of B-type natriuretic peptide for assessment of left ventricular
      function in patients with chronic kidney disease.
AB  - INTRODUCTION: Since the level of B-type natriuretic peptide (BNP) increases in
      heart failure, elevated plasma BNP concentration is used as a predictor in the
      diagnosis and management of heart failure. Due to the diminished renal clearance
      of BNP, its level is above normal in kidney failure. This study evaluated the BNP
      prognostic value for assessing ventricular function in patients with chronic
      kidney disease. MATERIALS AND METHODS: All the participants were diagnosed with
      chronic kidney disease. Echocardiography was employed to assess ejection
      fraction. Body mass index, serum creatinine, and BNP were measured for all the
      patients. Prognostic value of BNP was assessed for ventricular function measured
      by ejection fraction. RESULTS: Forty-four patients, including 34 men and 10
      women, participated in the study. Level of BNP had a significant correlation with
      body mass index, ejection fraction, age, and gender. The sensitivity and
      specificity of BNP levels of 150 pg/mL and 705 pg/mL were 93.3% and 28.6% and
      50.0% and 85.7%, respectively, for the diagnosis of ventricular dysfunction in
      the patients with chronic kidney disease. CONCLUSIONS: These findings suggest
      that a level of BNP of 705 pg/mL is a rather acceptable predictive factor for
      heart failure in patients with chronic kidney disease. The participants' height
      and weight, which were associated with BNP as body mass index, contributed to
      this level.

PMID- 21725182
TI  - Prevalence of metabolic syndrome in a hemodialysis population.
AB  - INTRODUCTION: The role of metabolic syndrome (MS) in hemodialysis population has
      not been thoroughly studied. This study aimed to determine the prevalence of MS
      and to identify its correlates among hemodialysis patients. MATERIALS AND
      METHODS: This cross-sectional study was conducted on patients in a hemodialysis
      center. The MS was defined according the Adult Treatment Panel III criteria.
      Clinical data of the patients were collected and blood samples were studied to
      measure fasting blood glucose and lipid profile. RESULTS: Eighty hemodialysis
      patients, including 47 men (58.8%) and 33 women (41.2%) with a mean age of 55.6
      +/- 15.6 years, were enrolled in this study. Metabolic syndrome was diagnosed in
      23 patients (28.7%). Hypertension was present in 55 patients (68.8%). Fifteen
      patients (18.8%) were diabetic, 24 (30.0%) had a high serum triglyceride, 22
      (27.5%) had a low high-density lipoprotein cholesterol, and 20 (25.0%) had
      evidence of abdominal obesity. Patients with MS had significantly higher body
      mass indexes (P < .001), fasting blood glucose levels (P < .001), and
      triglyceride levels (P = .004). Metabolic syndrome was not associated with
      gender, age, and duration of hemodialysis. Men showed significant abnormality in
      glucose metabolism (P = .008). Prevalence of low high-density lipoprotein
      cholesterol was significantly higher in the women than in the men (P = .02).
      CONCLUSIONS: The prevalence of MS in our hemodialysis patients was relatively
      high, with the most common element being hypertension. We suggest that there
      needs to be a new set of criteria defined for MS in hemodialysis patients.

PMID- 21725183
TI  - Measurement of serum levels of mannose-binding lectin in hemodialysis patients: a
      comparison with healthy individuals.
AB  - INTRODUCTION: Mannose-binding lectin (MBL) is a part of the innate immune system.
      Many studies showed an association of low serum MBL levels with decreased host
      defense against various infectious agents. Considering paradoxical reports about
      the serum level of MBL in hemodialysis patients, this study aimed to measure and
      compare serum MBL levels in hemodialysis patients and healthy individuals.
      MATERIALS AND METHODS: In a cross-sectional study, 70 hemodialysis patients and
      70 volunteers with normal routine laboratory tests and physical examination were
      assessed for serum MBL level (measured by an enzyme-linked immunosorbent assay).
      In addition, serum C-reactive protein levels in hemodialysis patients were
      measured to rule out correlation of increased serum MBL level with inflammation.
      RESULTS: In hemodialysis patients, 32 (45.7%) were men and 38 (54.3%) were women.
      In the control group, 34 (48.6%) were men and 36 (51.4%) were women (P = .87).
      The mean age showed no significant difference in hemodialysis (44.5 +/- 13.5
      year) and control (46.4 +/- 12.4 years) groups. Serum level of MBL was
      significantly higher in hemodialysis patients (2.12 +/- 1.49 microg/mL) than that
      in the controls (1.49 +/- 2.12 microg/mL; P < .001). No significant correlation
      was found between serum MBL and C-reactive protein levels (r = 0.002, P = .98)
      among the hemodialysis patients. CONCLUSIONS: Serum MBL level in hemodialysis
      patients was significantly higher than that in the control group of healthy
      individuals. This may have some implications in management of patients and
      prediction of kidney allograft survival.

PMID- 21725184
TI  - Correlation between heat-shock protein 27 serum concentration and common carotid
      intima-media thickness in hemodialysis patients.
AB  - INTRODUCTION: Cardiovascular disease is a major factor in the deterioration of
      the health and the death of hemodialysis patients. Previous studies have mainly
      shown a decreased level of heat shock protein 27 (HSP27) in patients with
      cardiovascular disease. We conducted this study to investigate whether HSP27
      correlates with common carotid intima-media thickness (CCIMT) and if it has a
      potential to be a biomarker for cardiovascular disease. MATERIALS AND METHODS: In
      this cross-sectional study, the correlation between HSP27 serum concentration and
      CCIMT was investigated in 42 hemodialysis patients. An enzyme-linked
      immunosorbent assay method was used to measure HSP27 level in the plasma of the
      patients, and a high-resolution B-mode ultrasonography was applied to measure
      CCIMT. RESULTS: There was an inverse significant correlation between serum
      concentration of HSP27 and CCIMT only in patients that had hypertension as their
      only cardiovascular risk factor (r = - 0.61, P = .02). CONCLUSIONS: According to
      our results and the fact that HSP27 has been shown to be expressed in
      atherosclerotic plaques of both experimental animals and humans, we suggest that
      circulatory HSP27 concentration has a potential of being used as a marker for
      cardiovascular events.

PMID- 21725185
TI  - Relationship between serum parathyroid hormone and hypertension in hemodialysis
      patients.
AB  - INTRODUCTION: Prevalence of hypertension is high in hemodialysis patients.
      Increase of intracellular calcium due to hyperparathyroidism is one of probable
      factors for hypertension in hemodialysis patients. In this study, the
      relationship between serum parathyroid hormone (PTH) level and severity of
      hypertension in hemodialysis patients was investigated. MATERIALS AND METHODS: In
      a case-control study, 50 hemodialysis patients with hypertension were compared
      with 50 hemodialysis patients without hypertension. The two groups were
      comparable in age, sex, body mass index, hemodialysis duration, KT/V, serum
      calcium, hemoglobin, and erythropoietin dose. Serum PTH level was measured in the
      two groups. RESULTS: The mean age was 57.0 +/- 7.7 years in the hypertensive
      group and 56.4 +/- 6.0 years in the control group (P = .61). The mean
      hemodialysis duration was 15.28 +/- 5.74 months in the hypertensive group and
      14.98 +/- 6.35 months in the control group. The mean serum PTH was 487.18 +/-
      408.85 pg/mL in hypertensives (445.12 +/- 447.92 pg/mL in stage 1 of hypertension
      and 561.94 +/- 326.67 pg/mL in stage 2 of hypertension, P = .003) and 170.64 +/-
      122.09 pg/mL in the case group (P = .001). CONCLUSIONS: According to this study,
      there is a positive relationship between serum PTH and severity of hypertension
      in hemodialysis patients. We conclude that control of secondary
      hyperparathyroidism might be helpful in controlling hypertension in hemodialysis
      patients.

PMID- 21725186
TI  - Progression and resolution of acute focal bacterial nephritis.
AB  - It is crucial that nephrologists correctly identify acute focal bacterial
      nephritis, as timely and adequate treatment with appropriate antibiotics can
      prevent unnecessary investigations, invasive surgical procedures, and renal
      complications such as renal abscess or renal scar. An urgent kidney
      ultrasonography should be performed if there is a delayed response to appropriate
      antibiotic treatment in patients with urinary tract infection. Serial kidney
      ultrasonography plays a significant role in confirming the diagnosis and
      monitoring the progression of acute focal bacterial nephritis. We presented a
      patient with acute focal bacterial nephritis and showed that a serial kidney
      ultrasonography could prevent the use of invasive investigations and
      inappropriate surgical procedures.

PMID- 21725187
TI  - Renal replacement lipomatosis with coexisting xanthogranulomatous pyelonephritis
      in a pregnant woman.
AB  - Renal replacement lipomatosis of the kidney is a rare entity characterized by
      renal sinus and perirenal fat proliferation often caused by renal calculi. Most
      of the renal parenchyma is replaced by fat and the kidney is usually small,
      atrophic and nonfunctioning. We report magnetic resonance imaging and
      ultrasonography findings of a pregnant woman with xanthogranulomatous
      pyelonephritis and renal replacement lipomatosis coexisting in the same kidney.

PMID- 21725188
TI  - Nephroquiz 6: a 67-year-old kidney transplant recipient with nephrotic-range
      proteinuria.

PMID- 21725191
TI  - Taking in the view from 30,000 feet.

PMID- 21725192
TI  - A guide to understanding meta-analysis.
AB  - With the focus on evidence-based practice in healthcare, a well-conducted
      systematic review that includes a meta-analysis where indicated represents a high
      level of evidence for treatment effectiveness. The purpose of this commentary is
      to assist clinicians in understanding meta-analysis as a statistical tool using
      both published articles and explanations of components of the technique. We
      describe what meta-analysis is, what heterogeneity is, and how it affects meta
      analysis, effect size, the modeling techniques of meta-analysis, and strengths
      and weaknesses of meta-analysis. Common components like forest plot
      interpretation, software that may be used, special cases for meta-analysis, such
      as subgroup analysis, individual patient data, and meta-regression, and a
      discussion of criticisms, are included.

PMID- 21725193
TI  - Coronoid process fracture.

PMID- 21725194
TI  - Lumbar synovial cyst.

PMID- 21725195
TI  - Structural LSI can occur in the absence of functional LSI.

PMID- 21725197
TI  - Neurotensin receptor-1 inducible palmitoylation is required for efficient
      receptor-mediated mitogenic-signaling within structured membrane microdomains.
AB  - Neurotensin receptor-1 (NTSR-1) is a G-protein coupled receptor (GPCR) that has
      been recently identified as a mediator of cancer progression. NTSR-1 and its
      endogenous ligand, neurotensin (NTS), are co-expressed in several breast cancer
      cell lines and breast cancer tumor samples. Based on our previously published
      study demonstrating that intact structured membrane microdomains (SMDs) are
      required for NTSR-1 mitogenic signaling, we hypothesized that regulated receptor
      palmitoylation is responsible for NTSR-1 localization and signaling within SMDs
      upon NTS stimulation. Site-directed mutagenesis and pharmacological strategies
      were utilized to assess NTRS-1 post-translational modifications in an over
      expression cell model (HEK293T) as well as a native breast cancer cell model (MDA
      MB-231). NTSR-1 palmitoylation was confirmed by multiple chemical and
      fluororadiographic methodologies. NTSR-1 glycosylation was confirmed by
      pharmacological (tunicamycin) and chemical (PGNaseF and O-type glycosidase)
      approaches. Physiological correlates including cell viability (MTS assay),
      apoptosis (caspase 3/7 assay) and ERK phosphorylation were utilized to assess the
      consequences of NTRS-1 palmitoylation. The interaction between palmitoylated NTRS
      1 and Galphaq/11 within SMDS was confirmed with immunopreciptation analysis of
      detergent-free isolated fractions of caveolin-rich microdomains. We identified
      dual-palmitoylation at Cys381 and Cys383 of endogenously-expressed NTSR-1 in MDA
      MB-231 breast adeno-carcinomas as well as exogenously-expressed NTSR-1 in HEK293T
      cells (which do not normally express NTSR-1). Pharmacological inhibition of NTSR
      1 palmitoylation in MDA-MB-231 cells as well as NTSR-1-expressing HEK293T cells
      diminished NTS-mediated ERK 1/2 phosphorylation. Additionally, NTSR-1 mutated at
      Cys381 and Cys383 showed diminished ERK1/2 stimulation and reduced ability to
      protect HEK293T cells against apoptosis induced by serum starvation.
      Mechanistically, mutated C381,383S-NTSR-1 showed reduced ability to interact with
      Galphaq/11 and diminished localization to structured membrane microdomains
      (SMDs), where Galphaq/11 preferentially resides. We also demonstrated that only
      glycosylated isoforms of NTRS-1 localize within SMDs by palmitotylation.
      Collectively, our data establish palmitoylation as a novel pharmacological target
      to inhibit NTSR-1 mitogenic signaling in breast cancer cells.

PMID- 21725198
TI  - Highlighting chromosome loops in DNA-picked chromatin (DPC).
AB  - Growing evidence supports the concept that dynamic intra- and inter-chromosomal
      links between specific loci contribute to the creation of cell-type specific gene
      expression profiles. Therefore, analysis of the establishment of peculiar
      functional correlations between sites, also distant on linear DNA, that govern
      the transcriptional process appears to be of fundamental relevance. We propose
      here an experimental approach showing that 17beta-estradiol-induced transcription
      associates to formation of loops between the promoter and termination regions of
      hormone-responsive genes. This strategy reveals as a tool to be also suitably
      used, in conjunction with automated techniques, for an extensive analysis of
      sites shared by multiple genes for induced expression.

PMID- 21725199
TI  - Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in
      the tumor stromal microenvironment.
AB  - As an integral component of the microenvironment in colorectal cancer (CRC),
      stromal cells can influence tumor progression. Found in the extracellular matrix
      of CRC, secreted protein acidic and rich in cysteine (SPARC) is expressed in
      stromal and CRC cells. While SPARC's influence on CRC is not clear, we
      hypothesized that epigenetically regulated SPARC expression in the
      microenvironment stromal cells of CRC can affect primary CRC progression and is
      influenced by lymphovascular invasion (LVI). Quantitative immunohistochemistry
      (IHC) analysis of paraffin-embedded (n=72) from 37 LVI-positive and 35 LVI
      negative primary CRCs was performed. MassARRAY sequencing was performed to assess
      the methylation status of the promoter region in 22 LVI-positive and 20 LVI
      negative CRC and to identify specific CpG island(s) regulating SPARC expression.
      SPARC in CRC cells was not correlated with LVI, whereas SPARC in the
      microenvironment stromal cells was inversely related to LVI (P < 0.0001). There
      was a direct relationship between LVI and 6 specific CpG site methylation in the
      SPARC promoter region of stromal cells (P = 0.017) but not in CRC cells. Stromal
      SPARC expression inversely correlated with VEGF-A expression in CRC (P = 0.003)
      and positively correlated with HSP27 expression (P = 0.009). The results
      suggested that the epigenetic regulation of SPARC expression in tumor cells
      versus stromal cells of CRC is significantly different. Stromal cell SPARC
      expression is epigenetically influenced by LVI of CRC tumors, and may play a
      significant role in primary CRC progression.

PMID- 21725200
TI  - The depletion of DNA methyltransferase-1 and the epigenetic effects of 5-aza
      2'deoxycytidine (decitabine) are differentially regulated by cell cycle
      progression.
AB  - 5-Aza-2'-deoxycytidine (decitabine) is a drug targeting the epigenetic
      abnormalities of tumors. The basis for its limited efficacy in solid tumors is
      unresolved, but may relate to their indolent growth, their p53 genotype or both.
      We report that the primary molecular mechanism of decitabine-depletion of DNA
      methyltransferase-1 following its "suicide" inactivation-is not absolutely
      associated with cell cycle progression in HCT 116 colon cancer cells, but is
      associated with their p53 genotype. Control experiments affirmed that the
      secondary molecular effects of decitabine on global and promoter-specific CpG
      methylation and MAGE-A1 mRNA expression were S-phase dependent, as expected.
      Secondary changes in CpG methylation occurred only in growing cells ~24-48 h
      after decitabine treatment; these epigenetic changes coincided with p53
      accumulation, an index of DNA damage. Conversely, primary depletion of DNA
      methyltransferase-1 began immediately after a single exposure to 300 nM
      decitabine and it progressed to completion within ~8 h, even in confluent cells
      arrested in G 1 and G 2/M. Our results suggest that DNA repair and remodeling
      activity in arrested, confluent cells may be sufficient to support the primary
      molecular action of decitabine, while its secondary, epigenetic effects require
      cell cycle progression through S-phase.

PMID- 21725201
TI  - Dynamics of DNA methylation levels in maternal and paternal rabbit genomes after
      fertilization.
AB  - The reprogramming of DNA methylation in early embryos has been considered to be
      essential for the reprogramming of differentiated parental genomes to
      totipotency, the transcription of embryonic genome activation (EGA) and
      subsequent development. However, its degree appears to differ as a function of
      species and it may be altered by the in vitro environment. While the rabbit is a
      pertinent model for species with a delayed EGA because both in vivo and in vitro
      developed embryos are easily available, the status of DNA methylation levels in
      both parental genomes after fertilization remains controversial. In order to
      generate precise data on the DNA methylation status in rabbit zygotes, we first
      of all defined five pronuclear (PN) stages during the first cell cycle and then
      classified in vivo and in vitro developed rabbit zygotes according to these PN
      stages. Using this classification we precisely quantified both methylated DNA and
      the total DNA content during the one cell stage. The quantification of methylated
      DNA, normalized for the total DNA content, showed that both pronuclei displayed
      distinct patterns of DNA methylation reprogramming. In the maternal pronucleus
      (MP) the methylation level remained constant throughout the one cell stage,
      thanks to maintenance methylation during the S phase. Conversely, in the paternal
      pronucleus (PP) partial demethylation occurred before replication, probably as a
      result of active DNA demethylation, while maintenance methylation subsequently
      occurred during the S phase. Interestingly, we showed that PP DNA methylation
      reprogramming was partially altered by the in vitro environment. Taken together,
      our approach evidenced that rabbit is one of the species displaying partial DNA
      demethylation in the PP, and for the first time demonstrated maintenance
      methylation activity in both pronuclei during the first S phase.

PMID- 21725202
TI  - Establishment of paternal allele-specific DNA methylation at the imprinted mouse
      Gtl2 locus.
AB  - The monoallelic expression of imprinted genes is controlled by epigenetic factors
      including DNA methylation and histone modifications. In mouse, the imprinted gene
      Gtl2 is associated with two differentially methylated regions: the IG-DMR, which
      serves as a gametic imprinting mark at which paternal allele-specific DNA
      methylation is inherited from sperm, and the Gtl2-DMR, which acquires DNA
      methylation on the paternal allele after fertilization. The timeframe during
      which DNA methylation is acquired at secondary DMRs during post-fertilization
      development and the relationship between secondary DMRs and imprinted expression
      have not been well established. In order to better understand the role of
      secondary DMRs in imprinting, we examined the methylation status of the Gtl2-DMR
      in pre- and post-implantation embryos. Paternal allele-specific DNA methylation
      of this region correlates with imprinted expression of Gtl2 during post
      implantation development but is not required to implement imprinted expression
      during pre-implantation development, suggesting that this secondary DMR may play
      a role in maintaining imprinted expression. Furthermore, our developmental
      profile of DNA methylation patterns at the Cdkn1c- and Gtl2-DMRs illustrates that
      the temporal acquisition of DNA methylation at imprinted genes during post
      fertilization development is not universally controlled.

PMID- 21725203
TI  - Neuroblastoma epigenetics: from candidate gene approaches to genome-wide
      screenings.
AB  - Neuroblastoma (NB) is a childhood tumor originating from sympathetic nervous
      system cells. Although recently new insights into genes involved in NB have
      emerged, the molecular basis of neuroblastoma development and progression still
      remains poorly understood. The best-characterized genetic alterations include
      amplification of the proto-oncogene MYCN, ALK activating mutations or
      amplification, gain of chromosome arm 17q and losses of 1p, 3p, and 11q.
      Epigenetic alterations have been described as well: caspase-8 (CASP8) and RAS
      association domain family 1 isoform A (RASSF1A) DNA-methylation are important
      events for the development and progression of neuroblastoma. In total, there are
      about 75 genes described as epigenetically affected in NB cell lines and/or NB
      primary samples. These epigenetic alterations were either found using a candidate
      gene approach or based on the analysis of genome-wide screening techniques. This
      review gives an extensive overview of all epigenetic changes described in NB as
      of today, with a main focus on both prognostic use and the potential of genome
      wide techniques to find epigenetic prognostic biomarkers in NB. We summarize the
      key findings so far and the state-of-the-art of the upcoming methods at a unique
      time frame in the transition towards combined genome wide chromatin immune
      precipitation (ChIP) and DNA sequencing techniques.

PMID- 21725205
TI  - Soil microbes regulate ecosystem productivity and maintain species diversity.
AB  - One of the major goals in ecology is to determine the mechanisms that drive the
      asymptotic increase in ecosystem productivity with plant species diversity. Niche
      complementarity, the current paradigm for the asymptotic diversity-productivity
      pattern, posits that the addition of species to a community increases
      productivity because each species specializes on different resources and thus can
      more thoroughly utilize the available resources. At higher diversity the increase
      in productivity decreases because resources become limiting, resulting in the
      classic asymptotic diversity-productivity pattern. An alternative but less tested
      explanation is that density-dependent disease from species-specific soil microbes
      drive the diversity-productivity relationship by increasing disease and thus
      decreasing productivity at low diversity. At higher diversity, productivity
      asymptotes because disease decreases with increasing diversity until it reaches a
      uniformly low level. Using a series of field experiments, we found that the
      classic asymptotic diversity-productivity pattern existed only when soil microbes
      were present. Soil microbes created the well-known pattern by depressing plant
      growth at low productivity though negative density dependent disease. In
      contrast, niche complementarity played only a weak role in explaining the
      diversity-productivity relationship because productivity remained high at low
      abundance in the absence of soil microbes. Based on our findings, the ongoing
      loss of species in natural ecosystems will likely increase per capita plant
      disease and lower ecosystem productivity. Furthermore, recent evidence suggests
      that negative density dependent disease maintains plant species diversity, and
      thus this single mechanism appears to link diversity maintenance to the diversity
      productivity curve--two important ecological processes.

PMID- 21725204
TI  - Differential vitamin D 24-hydroxylase/CYP24A1 gene promoter methylation in
      endothelium from benign and malignant human prostate.
AB  - Epigenetic alterations occur in tumor-associated vessels in the tumor
      microenvironment. Methylation of the CYP24A1 gene promoter differs in endothelial
      cells isolated from tumors and non-tumor microenvironments in mice. The
      epigenetic makeup of endothelial cells of human tumor-associated vasculature is
      unknown due to difficulty of isolating endothelial cells populations from a
      heterogeneous tissue microenvironment. To ascertain CYP24A1 promoter methylation
      in tumor-associated endothelium, we utilized laser microdissection guided by CD31
      immunohistochemistry to procure endothelial cells from human prostate tumor
      specimens. Prostate tissues were obtained following robotic radical prostatectomy
      from men with clinically localized prostate cancer. Adjacent histologically
      benign prostate tissues were used to compare endothelium from benign versus tumor
      microenvironments. Sodium bisulfite sequencing of CYP24A1 promoter region showed
      that the average CYP24A1 promoter methylation in the endothelium was 20% from the
      tumor microenvironment compared with 8.2% in the benign microenvironment (p<
      0.05). A 2-fold to 17-fold increase in CYP24A1 promoter methylation was observed
      in the prostate tumor endothelium compared with the matched benign prostate
      endothelium in four patient samples, while CYP24A1 remained unchanged in two
      patient sample. In addition, there is no correlation of the level of CYP24A1
      promoter methylation in prostate tumor-associated endothelium with that of
      epithelium/stroma. This study demonstrates that the CYP24A1 promoter is
      methylated in tumor-associated endothelium, indicating that epigenetic
      alterations in CYP24A1 may play a role in determining the phenotype of tumor
      associated vasculature in the prostate tumor microenvironment.

PMID- 21725206
TI  - Circulating tumor cells count and characterization in a male breast cancer
      patient.
AB  - A 64-y-old man presented to Medical Oncology Department a metastatic invasive
      ductal breast carcinoma, positive for estrogen (ER) and progesterone receptors
      (PR) and Her2/neu negative. The patient was treated with different lines of
      therapy, with rapid radiological progression of disease. After four courses of a
      third-line chemotherapy, a radiological stable disease was maintained. The
      patient was followed by serial blood drawings for the characterization and count
      of circulating tumor cells (CTC). This is the first report concerning the
      predictive and prognostic value of CTC in a male breast cancer patient.

PMID- 21725207
TI  - Interferon-alpha sensitizes human gastric cancer cells to TRAIL-induced apoptosis
      via activation of the c-CBL-dependent MAPK/ERK pathway.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of
      the tumor necrosis factor family that induces apoptosis in cancer cells. However,
      gastric cancer cells are insensitive to TRAIL. In the present study, we show that
      pretreatment with IFN-alpha enhanced TRAIL-induced apoptosis of gastric cancer
      MGC803 cells. IFN-alpha up-regulated death receptor 5 (DR5) expression and down
      regulated survivin expression. Furthermore, extracellular-regulated protein
      kinase (ERK1/2) activation was induced by IFN-alpha, and a combination of IFN
      alpha and TRAIL led to further activation of ERK1/2. Inhibition of the MAPK/ERK
      signaling pathway partially reversed apoptosis, as well as the expression
      patterns of DR5 and survivin. Moreover, the expression of the c-casitas B-lineage
      lymphoma (c-Cbl) family was down-regulated by IFN-alpha. Transfection of c-Cbl
      suppressed IFN-alpha-induced ERK activation. These results indicate that IFN
      alpha enhances TRAIL-induced apoptosis in gastric cancer cells at least partially
      via downregulation of c-Cbl, and subsequent up-regulation of the MAPK/ERK
      pathway.

PMID- 21725208
TI  - p34 (SEI-1) inhibits ROS-induced cell death through suppression of ASK1.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a key factor for controlling
      several cellular events including the cell cycle, senescence and apoptosis, in
      response to reactive oxygen species (ROS). However, the mechanisms that regulate
      ASK1 protein levels remain largely unexplored. In this study, we demonstrate that
      p34 (SEI-1) , a positive cell cycle regulator with an oncogenic potential,
      inhibits ROS-induced cell death by suppressing ASK1. We first found that p34 (SEI
      1) -expressing cells have enhanced resistance to hydrogen peroxide (H 2O 2).
      Moreover, ectopic expression of p34 (SEI-1) clearly inhibited H 2O 2-induced
      phosphorylation of ASK1 in the colon cancer cell lines- HCT116 and SW620-in
      association with a decrease in ASK1 protein levels. Interestingly, p34 (SEI-1)
      induced ubiquitination of ASK1, however, no direct interaction was found between
      p34 (SEI-1) and ASK1. These results suggest that p34 (SEI-1) inhibits ROS-induced
      cell death through by indirectly inducing ubiquitination of ASK1.

PMID- 21725209
TI  - Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab.
AB  - The epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor
      tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in
      many human tumors. Currently there are five EGFR inhibitors used in oncology, two
      monoclonal antibodies (panitumumab, and cetuximab) and three tyrosine kinase
      inhibitors (erlotinib, gefitinib, and lapatinib). Both strategies of EGFR
      inhibition have demonstrated clinical successes, however many tumors remain non
      responsive or acquire resistance during therapy. To explore potential molecular
      mechanisms of acquired resistance to cetuximab we previously established a series
      of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell
      line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a
      dramatic increase in steady-state expression of EGFR, HER2, and HER3 receptors as
      well as increased signaling through the MAPK and AKT pathways. RNAi studies
      demonstrated dependence of cetuximab-resistant clones on the EGFR signaling
      network. These findings prompted investigation on whether or not cells with
      acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI
      erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR
      axis, decrease cellular proliferation, and induce apoptosis. To determine if
      erlotinib could have therapeutic benefit in vivo, we established cetuximab
      resistant NCI-H226 mouse xenografts, and subsequently treated them with
      erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib
      exhibited either a tumor regression or growth delay as compared to vehicle
      controls. Analysis of the erlotinib treated tumors demonstrated a decrease in
      cell proliferation and increase rates of apoptosis. The work presented herein
      suggests that 1) cells with acquired resistance to cetuximab maintain their
      dependence on EGFR and 2) tumors developing resistance to cetuximab can benefit
      from subsequent treatment with erlotinib, providing rationale for its use in the
      setting of cetuximab resistance.

PMID- 21725210
TI  - Sunitinib inhibits papillary thyroid carcinoma with RET/PTC rearrangement but not
      BRAF mutation.
AB  - Sunitinib, a multi-targeted tyrosine kinase inhibitor, is frequently incorporated
      into the management of papillary thyroid carcinoma refractory to standard
      therapies. Although clinical trials are in progress, the mechanism of action in
      papillary thyroid carcinomas is not clear, especially regarding the effect on
      BRAF mutation. We investigated the effect of sunitinib on papillary thyroid
      carcinoma cells harboring RET/PTC rearrangement and BRAF mutation using TPC-1M,
      SNU-790, and B-cPAP cell lines. Cell growth of papillary thyroid cancer cells
      with RET/PTC rearrangement was effectively inhibited at low doses of sunitinib
      (IC50=0.658 MUM), whereas that of BRAF mutated cells required higher doses.
      Immunoblotting revealed effective blocking of MEK/ERK pathway in RET/PTC
      rearrangement cells, but not in BRAF mutated cells. Cell cycle analysis showed G1
      arrest in RET/PTC rearrangement cells. In vivo orthotopic thyroid cancer mouse
      model demonstrated statistically significant tumor growth inhibition by sunitinib
      in RET/PTC rearrangement cancer cells. We conclude that sunitinib effectively
      inhibits RET/PTC rearrangement cells but not BRAF mutated cells. These data
      suggest that sunitinib exerts its effect by inhibiting the upstream MAPK
      signaling cascade. These findings support the unsatisfactory treatment outcomes
      of sunitinib in many already ongoing clinical trials compared to other tyrosine
      kinase inhibitors. Clinical application of sunitinib should be directed
      accordingly.

PMID- 21725211
TI  - Vesicle transfer and cell fusion: Emerging concepts of cell-cell communication in
      the tumor microenvironment.
AB  - Cell-cell fusion and vesicle-mediated transfer are fundamental biological
      processes that are emerging as novel mechanisms for re-programming cells in the
      tumor microenvironment. Both cell-cell fusion and intercellular transfer of
      vesicles (including microvesicles and exosomes) allow for the transfer of
      information among tumor cells, between tumor cells and tumor stroma, and between
      tumor cells and the host immune system, which could have profound implications
      for our understanding of tumor initiation and progression. The National Cancer
      Institute's Division of Cancer Biology sponsored a recent workshop (December 4-6,
      2010) entitled, Vesicle Transfer and Cell Fusion: Emerging Concepts of Cell-Cell
      Communication in the Tumor Microenvironment to assess the current state of the
      science in these two scientific areas. Co-chaired by Drs. Huang-Ge Zhang
      (University of Louisville) and Madhav Dhodapkar (Yale University) this workshop
      brought together, for the first time at the NIH, leaders in the field to assess
      the effects of vesicle transfer and cell-cell fusion on cancer initiation,
      progression and metastasis. This meeting report includes brief summaries of the
      presentations and identifies the major questions, roadblocks, and opportunities.
      The meeting report is presented here to highlight research priorities and to
      stimulate basic and translational research efforts to better understand the
      contributions of cell-cell fusion and vesicle transfer to cancer.

PMID- 21725212
TI  - Quinacrine sensitizes hepatocellular carcinoma cells to TRAIL and
      chemotherapeutic agents.
AB  - Quinacrine has been widely explored in treatment of malaria, giardiasis, and
      rheumatic diseases. We find that quinacrine stabilizes p53 and induces p53
      dependent and independent cell death. Treatment by quinacrine alone at
      concentrations of 10-20 mM for 1-2 d cannot kill hepatocellular carcinoma cells,
      such as HepG2, Hep3B, Huh7, which are also resistant to TRAIL. However,
      quinacrine renders these cells sensitive to treatment by TRAIL. Co-treatment of
      these cells with quinacrine and TRAIL induces overwhelming cell death within 3-4
      h. Levels of DR5, a pro-apoptotic death receptor of TRAIL, are increased upon
      treatment with quinacrine, while levels of Mcl-1, an anti-apoptotic member of the
      Bcl-2 family, are decreased. While the synergistic effect of quinacrine with
      TRAIL appears to be in part independent of p53, knockdown of p53 in HepG2 cells
      by siRNA results in more cell death after treatment by quinacrine and TRAIL. The
      mechanism by which quinacrine sensitizes hepatocellular carcinoma cells to TRAIL
      and chemotherapies, and the potential for clinical application currently are
      being further explored. Lastly, quinacrine synergizes with chemotherapeutics,
      such as adriamycin, 5-FU, etoposide, CPT11, sorafenib, and gemcitabine, in
      killing hepatocellular carcinoma cells in vitro and the drug enhances the
      activity of sorafenib to delay tumor growth in vivo.

PMID- 21725213
TI  - Quinacrine synergizes with 5-fluorouracil and other therapies in colorectal
      cancer.
AB  - Although treatments have improved patient prognosis in surgically resectable
      colorectal cancer, new effective drugs with improved safety profiles are needed
      to improve the currently poor outcomes of patients with recurrent or metastatic
      colorectal cancer. Quinacrine, a small molecule anti-malarial agent that has
      activity in giardiasis, lupus, prion disease, and used as a means of non-surgical
      sterilization, has shown cytotoxic activity across a broad range of cancers.
      Here, we evaluate the potential of adding quinacrine to anticancer
      chemotherapeutics and targeted agents as a potential novel combinatorial therapy
      for advanced colon cancer. We show that quinacrine synergizes with 5-fluorouracil
      and significantly enhances the cytotoxicity of sorafenib in a panel of 10 human
      colorectal cancer cell lines, including those with KRAS mutations protein gel
      blot analysis confirmed that quinacrine's anticancer activity partially arises
      from its ability to stabilize p53 and lower anti-apoptotic protein levels. In a
      series of in vivo studies, quinacrine monotherapy lowered the tumor load of nu/nu
      mice bearing human colorectal cancer xenografts. In combination, quinacrine and 5
      Fluorouracil significantly delayed tumor growth of a variety of different
      xenografts, as compared to each agent administered alone. Our results suggest
      that the administration of quinacrine in combination with chemotherapeutic agents
      and targeted agents should be further explored in patients with recurrent,
      locally advanced, or metastatic colorectal cancer.

PMID- 21725214
TI  - From the editor.

PMID- 21725215
TI  - "The people not the policy": quality improvement, junior doctors, and cultural
      change.
AB  - BACKGROUND: Health care is a highly regulated environment. This has driven what
      could be characterized as a paper-safe approach, whereby organizations are
      required to demonstrate to a multiplicity of regulators, inspectorates, and
      accrediting bodies that they are paper safe. However, for many organizations,
      this has not produced a system that is actually patient safe; rather, it has in
      practice operated as a parallel system that does not reflect the true state of
      safety. This project looks at a quality improvement and patient safety program
      and critically asks the question of whether it is flawed because of failure to
      address issues surrounding doctors and cultural change. METHODS: Johnson &
      Schole's cultural web framework was used to explore the attitudes of junior
      doctors toward a patient safety and quality improvement program. Data collection
      was through the use of focus groups backed up with quantitative data from a web
      based questionnaire survey. RESULTS: It has been demonstrated that doctors
      represent a dominant subculture within the National Health Service and their
      beliefs, attitudes, and value are often at odds or unrecognized by senior health
      care managers. CONCLUSIONS: Unless the cultural differences are adequately
      addressed, transformational change projects such as "Best & Safest Care" are
      unlikely to succeed. A better understanding of the organizational context allows
      for more appropriate change interventions to be developed.

PMID- 21725216
TI  - The hospital is not your home: making safety safer (Swiss cheese is a culinary
      missed metaphor).

PMID- 21725217
TI  - Using the "customer service framework" to successfully implement patient- and
      family-centered care.
AB  - Despite the growing momentum toward patient- and family-centered care at the
      federal policy level, the organizational literature remains divided on its
      effectiveness, especially in regard to its key dimension of involving patients
      and families in treatment decisions and safety practices. Although some have
      argued for the universal adoption of patient involvement, others have questioned
      both the effectiveness and feasibility of patient involvement. In this article,
      we apply a well-established theoretical perspective, that is, the Service Quality
      Model (SQM) (also known as the "customer service framework") to the health care
      context, to reconcile the debate related to patient involvement. The application
      helps support the case for universal adoption of patient involvement and also
      question the arguments against it. A key contribution of the SQM lies in
      highlighting a set of fundamental service quality determinants emanating from
      basic consumer service needs. It also provides a simple framework for
      understanding how gaps between consumer expectations and management perceptions
      of those expectations can affect the gap between "expected" and "perceived"
      service quality from a consumer's perspective. Simultaneously, the SQM also
      outlines "management requirements" for the successful implementation of a
      customer service strategy. Applying the SQM to the health care context therefore,
      in addition to reconciling the debate on patient involvement, helps identify
      specific steps health care managers could take to successfully implement patient-
      and family-centered care. Correspondingly, the application also provides insights
      into strategies for the successful implementation of policy recommendations
      related to patient- and family-centered care in health care organizations.

PMID- 21725218
TI  - The best period for mortality rates associated with hospital stay: hospital
      mortality performs well for nonsurgical diagnostic groups.
AB  - BACKGROUND: Mortality is widely used to assess quality of hospital care.
      Inpatient mortality is easily available in administrative data. The use of
      periods other than length of stay is questionable. We compared different
      overlapping and disjunctive periods for the calculation of mortality associated
      with hospital care. SUBJECTS AND METHODS: Information from public quality reports
      covering insured from local sickness funds were retrospectively recorded.
      Nineteen thousand eight hundred thirteen patients from 69 hospitals were included
      for 5 tracers. The relationship between different periods, or time spans from
      admission to death or discharge, was assessed calculating the nonparametric
      correlation coefficient for mortality rates and standardized mortality ratios.
      The periods were hospital stay, 30, 90, and 365 days after admission, 31 to 90
      days, and 91 to 365 days. The variation within each period was assessed with the
      coefficient of variation. RESULTS: There is a strong relationship between
      overlapping periods for nonsurgical tracers with r > 0.559 (P < .001). The
      surgical tracers present a reverse relationship between 30-day and 91-day to 365
      day mortality with r = -0.724 (P = .012) for colorectal carcinoma with operation
      and r = -0.490 (P = .028) for total hip replacement in case of femur fracture.
      Nonsurgical tracers show a decreasing variation of mortality rates with extending
      periods, whereas colorectal carcinoma shows a stable and small variation.
      CONCLUSIONS: For nonsurgical tracers, hospital stay is the best period to assess
      mortality associated with hospital stay. The courses (sequences of 4 mortality
      rates for one tracer in a hospital) for surgical tracers, in particular
      colorectal carcinoma, appear as a harvesting effect with an association of high
      in-hospital mortality with low mortality in the medium term.

PMID- 21725219
TI  - Bayesian change point detection in monitoring cardiac surgery outcomes.
AB  - Precise identification of the time when a clinical process has changed, a control
      chart's signal, enables clinicians to search for a potential special cause more
      effectively. In this article, we develop a change point estimation method for
      Bernoulli processes in a Bayesian framework. We apply Bayesian hierarchical
      models to formulate the change point model and Markov Chain Monte Carlo to obtain
      posterior distributions of the change point parameters. The performance of the
      Bayesian estimator is investigated through applications on clinical data. We
      monitor outcomes of cardiac surgery and angioplasty procedures using Bernoulli
      exponentially weighted moving average (EWMA) and cumulative sum (CUSUM) control
      charts. We then identify the time of changes in prior signals obtained from
      charts. Study of the known potential causes of changes in the outcomes reveals
      that estimated change points and shifts in the known causes are coincident.

PMID- 21725220
TI  - Facilitators and barriers to the implementation of patient flow improvement
      strategies.
AB  - Patient flow improvement strategies have been effective in reducing emergency
      department (ED) crowding, but little guidance is available on the implementation
      process. By using a qualitative research design, our objective was to identify
      common facilitators and barriers to the implementation of patient flow
      improvement strategies and successful approaches for mitigating barriers. Six
      hospitals participated in an 18-month Urgent Matters learning network launched in
      October 2008. The hospitals selected strategies to improve patient flow that
      could be implemented within 3 months with measurable impact. Across 6 hospitals,
      8 strategies were implemented. We conducted 2 rounds of key informant interviews
      with improvement teams, for a total of 129 interviews. Interviews were recorded,
      transcribed, and coded by using a grounded theory approach to identify common
      themes. Factors facilitating implementation included participation in the
      learning network and strategic selection of team members. Common challenges
      included staff resistance and entrenched organizational culture. Some of the
      challenges were mitigated through approaches such as staff education and
      department leaders' constant reinforcement. Our findings indicate that several
      facilitators and barriers are common to the implementation of different
      strategies. Leveraging facilitators and developing a strategy to address common
      barriers may leave hospital and ED leaders better prepared to implement patient
      flow improvement strategies.

PMID- 21725221
TI  - "Pay-for-performance" as a quality improvement tool: perceptions and policy
      recommendations of physicians and program leaders.
AB  - BACKGROUND: Although pay-for-performance (P4P) compensation is widespread,
      questions have arisen about its efficacy in improving health care quality and
      consequences for vulnerable patients. OBJECTIVE: To assess perceptions of general
      internists and P4P program leaders regarding how to implement fair and effective
      P4P. METHODS: Qualitative investigation using in-depth interviews with P4P
      program leaders and focus groups with general internists. RESULTS: Internists
      emphasized a gradual and cautious approach to P4P implementation. They strongly
      recommended improving P4P measure validity and had detailed suggestions regarding
      how. Program leaders saw a need to implement perhaps imperfect programs but with
      continual improvement. Both groups advocated protecting vulnerable populations
      and made overlapping recommendations: improving measure validity; adjusting for
      patient characteristics; measuring improvements in quality (vs cutpoints); and
      providing incentives to physicians of vulnerable populations. Internists tended
      to favor explicit protections, while program leaders felt that P4P might
      inherently protect vulnerable patients by improving overall quality. DISCUSSION:
      Internists favored gradual P4P implementation, while P4P leaders saw an immediate
      need for implementation with iterative improvement. Both groups recommended
      specific measures to protect vulnerable populations such as improving measure
      validity, assessing improvements in quality, and providing special incentives to
      physicians of vulnerable populations.

PMID- 21725222
TI  - Response to Forsberg et al (2011). Managing health care decisions and improvement
      through simulation modeling: modeling versus modelling.

PMID- 21725225
TI  - Assessing chronological age of unaccompanied minors in southern Italy.
AB  - The increasing volume of, and subsequent complexities resulting from, migratory
      flows in the broader context of globalization has led to a range of problems, not
      only the protection of human rights and disease control but also the
      identification of those with the right to apply for refugee status and the age
      assessment of unaccompanied minors. Italy is a magnet for immigration from other
      countries bordering the Mediterranean Sea because the Italian coasts are within
      easy reach. In Italy, as in other western countries, unaccompanied asylum seekers
      deemed to be younger than 18 years face a very different path through the
      immigration system from that experienced by adults. Generally, adults are subject
      to immediate deportation or detention in jail. Minors are processed through the
      juvenile system, where detection is not mandatory; they will often have access to
      educational programs and may be granted a residency permit. The Section of Legal
      Medicine of the University of Bari was approached by immigration police
      authorities and judges to explore the possibility of examining unaccompanied
      asylum seekers, who claim do be younger than 18 years, to assess their age. A
      group of forensic pathologists and odontologists performed this evaluation
      relying on the skeletal maturation as seen on radiographs of the wrist and the
      pelvis for iliac crests and on an orthopantomograph, together with background
      information and clinical examination of each individual. Case studies are
      presented. This article does not attempt to give a definitive account of the
      different scientific methods for the assessment of age. It is important to
      understand some of the methods that may be used in an attempt to assess
      developmental maturity and from which it may be possible to "read off" an
      approximate chronological age.

PMID- 21725226
TI  - Laryngohyoid and cervical vertebra lesions after a fall from a low height.
AB  - The aim of this study was to determine the frequency and nature of cervical
      trauma in the case of low-height falls (up to 2.50 m). A retrospective study was
      carried out on 114 autopsy cases that died after low-height falls. For each case,
      age, sex, manner and cause of death, estimated height of fall, ground type, type
      of primary impact, type of laryngeal and hyoid bone trauma, presence of
      associated local trauma in the neck and cephalic region, and toxicological data
      were reported. Fractures of the hyoid bone and/or of the laryngeal cartilages
      were present in 2.5% of the cases (n = 3). Cervical soft tissue bruising was
      found in 13% of the cases (n = 15). About 6% of the cases (n = 7) showed blunt
      cervical vertebral column trauma, including 3 cases with ruptured intervertebral
      disk. Interpretation and mechanisms of these lesions are discussed.

PMID- 21725227
TI  - Multidisciplinary investigation of an unusual apparent homicide/suicide.
AB  - The investigation of deaths of individuals whose bodies are decomposed,
      mummified, or skeletonized is particularly difficult for medical examiners and
      medicolegal death investigators. Determination of the cause and manner of death
      in such cases frequently requires consultation with experts in a variety of
      disciplines in the forensic sciences and necessitates correlation of the autopsy
      results, scene investigation, medical and social history of the deceased, and
      laboratory studies. The authors report an unusual case of an apparent
      homicide/suicide involving 2 individuals and a canine that went undetected for
      almost 4 years. Determination of the cause and manner of death in these cases
      involved a multidisciplinary, intercontinental investigation and necessitated the
      performance of toxicologic studies on specimens not commonly analyzed. These
      cases illustrate the importance of the multidisciplinary approach to medicolegal
      death investigations and the necessity of considering nontraditional sources of
      potential information and specimens for laboratory analysis in selected cases. 

PMID- 21725228
TI  - Origin and development of forensic medicine in the Kingdom of Saudi Arabia.
AB  - The medicolegal death investigation system in the Kingdom of Saudi Arabia (KSA)
      is unique in the world. It is exclusively derived from Islamic judiciary based on
      Shari'ah law, which is the definitive Islamic law or doctrine. This law is
      applied on Saudi citizens as well as foreigners. This is different from other
      Islamic countries, which have a combination of Islamic and other judiciary
      systems.The forensic medicine centers in KSA are related administratively to the
      Ministry of Health (MOH) and its subdivisions in the different governorates. They
      are concerned with forensic medical examination and autopsy, as well as the
      clinical forensic medical examination of sexual assault cases, and those injured
      in civil and criminal cases. The assisting laboratories (forensic histopathology,
      microbiology, serology, forensic chemistry) are working independently under the
      funding of MOH, whereas the DNA laboratory and other departments of forensic
      sciences, for example, counterfeiting and forgery unit are related
      administratively to the Ministry of Interior represented by the Administration of
      Criminal Evidences. Efforts concerning crime scene investigations are shared with
      Administration of Criminal Evidences' crime scene investigators.Forensic medicine
      education in KSA developed in the past few years after the foundation of Saudi
      specialty certificate in forensic medicine. The certificate is a postgraduation
      qualification equivalent to a doctorate degree in forensic medicine and requires
      completion of a 4-year training program in both MOH- and Ministry of Interior
      related departments, as well as passing annual evaluation and examination.This
      review is aimed at providing in the next decade the medicolegal centers with
      national forensic specialists throughout the kingdom and granting skillful
      headships for the next generations. Moreover, this review suggests more
      scientific associations with the academic universities in the various fields of
      forensic sciences through academic cooperation.

PMID- 21725229
TI  - Numbers, sizes, and types of diatoms around estuaries for a diatom test.
AB  - We collected 68 fresh, brackish, and seawater samples from various sites around
      the estuaries of 2 rivers at high and low tides. Seawater flowed approximately
      2.4 (salinity, 2.2% at the site) and 1.2 km (1.8%) upstream of the estuaries, but
      the surface comprised essentially fresh water up to the mouth. Sites contained 69
      to 22,200 diatoms/50 mL of water, and the numbers varied by depth and at sites
      separated by only approximately 1.2 km. Diatoms ranged from 2.8 to 429 MUm (mean
      range, 16.1-59.2 MUm) in size. Large pennate diatoms populated fresh water areas,
      and most sedimented before reaching the sea. Numbers of pennate diatoms of less
      than 20 MUm were decreased in areas of seawater. Numbers of centric diatoms
      tended to increase nearer the sea, and seawater contained large centric diatoms.
      Brackish water containing large volumes of seawater was easily discriminated by
      assemblages of marine diatoms, unlike that containing a little seawater, because
      marine diatoms could be found in fresh water around estuaries. Tides and the
      nature of the river often altered diatomaceous assemblages at the same estuarial
      sites. Caution is recommended for forensic interpretation of aqueous media to
      deduce drowning sites. 

PMID- 21725230
TI  - End-to-end versus end-to-side esophagogastrostomy after esophageal cancer
      resection: a prospective randomized study.
AB  - OBJECTIVE: To compare single-layered hand-sewn cervical end-to-side (ETS)
      anastomosis with end-to-end (ETE) anastomosis in a prospective randomized
      fashion. BACKGROUND: The preferred organ used for reconstruction after
      esophagectomy for cancer is the stomach. Previous studies attempted to define the
      optimal site of anastomosis and anastomotic techniques. However, anastomotic
      stricture formation and leakage still remain an important clinical problem.
      METHODS: From May 2005 to September 2007, 128 patients (64 in each group) were
      randomized between ETE and ETS anastomosis after esophagectomy for cancer with
      gastric tube reconstruction. Routine contrast swallow studies and endoscopy were
      performed. Anastomotic stricture within 1 year, requiring dilatation, was the
      primary endpoint. Secondary endpoints were anastomotic leak rate and mortality.
      RESULTS: Ninety-nine men and 29 women underwent esophagectomy and gastric tube
      reconstruction. Benign stenosis of the anastomosis, for which dilatation was
      required, occurred more often in the ETE group (40% vs. ETS 18%, P < 0.01) after
      1 year of follow-up. The overall (clinical and radiological) anastomotic leak
      rate was lower in the ETE group (22% vs. ETS 41%, P = 0.04). Patients with an ETE
      anastomosis suffered less often from pneumonia; 17% versus ETS 44%, P = 0.002 and
      had subsequently significantly shorter in-hospital stay (15 days vs. 22 days, P =
      0.02). In-hospital mortality did not differ between both groups. CONCLUSION: ETS
      anastomosis is associated with a lower anastomotic stricture rate, compared to
      ETE anastomosis. However, prevention of stricture formation was at high costs
      with increased anastomotic leakage and longer in-hospital stay. This study is
      registered with the Dutch Trial Registry and carries the ID number OND1317772.

PMID- 21725231
TI  - Clinical outcome of a randomized controlled blinded trial of open versus
      laparoscopic Nissen fundoplication in infants and children.
AB  - OBJECTIVE: To compare the clinical outcome and endocrine response in children who
      were randomized to open or laparoscopic Nissen fundoplication using minimization.
      BACKGROUND: It is assumed that laparoscopic surgery is associated with less pain,
      quicker recovery and dampened endocrine response. Few randomized studies have
      been performed in children. METHODS: Parents gave informed consent, and this
      study was approved and registered (ClinicalTrials.gov Identifier: NCT00231543).
      Anesthesia, postoperative analgesia and feeding were standardized. Parents and
      staff were blinded to allocation. Blood was taken for markers of endocrine
      response. RESULTS: Twenty open and 19 laparoscopic patients were comparable with
      respect to age, weight, neurological status, and presence of congenital
      anomalies. Median time to full feeds was 2 days in both groups (P = 0.85);
      hospital stay was 4.5 days in the open group versus 5.0 days in the laparoscopic
      group (P = 0.57). Pain was adequately managed in both groups and there was no
      difference in morphine requirements. Median follow-up was 22 (range 12-34)
      months. Dysphagia, recurrence and need for redo fundoplication were not different
      between groups; retching was higher after open surgery (56% vs. 6%; P = 0.003).
      Insulin levels decreased at 24 hours, and was 54% lower (P = 0.02) after
      laparoscopy. Cortisol was elevated immediately postoperative, but was 42% lower
      (P = 0.02) after laparoscopy. CONCLUSIONS: There was no difference in the
      postoperative analgesia requirements and recovery. Laparoscopy decreased insulin
      levels to a greater extent, but caused less of a response in cortisol. Early
      postoperative outcome confirmed equal efficacy, but fewer children with retching
      after laparoscopy.

PMID- 21725232
TI  - Role of acid-sensing ion channel 1a in the secondary damage of traumatic spinal
      cord injury.
AB  - OBJECTIVE: To determine the cellular and molecular mechanisms by which acid
      sensing ion channel 1a (ASIC1a) plays its role in the secondary injury after
      traumatic spinal cord injury (SCI), and validate the neuroprotective effect of
      ASIC1a suppression in SCI model in vivo. BACKGROUND: Secondary damage after
      traumatic SCI contributes to the exacerbation of cellular insult and thereby
      contributes to spinal cord dysfunction. However, the underlying mechanisms remain
      largely unknown. Acidosis is commonly involved in the secondary injury process
      after the injury of central nervous system, but whether ASIC1a is involved in
      secondary injury after SCI is unclear. METHODS: Male Sprague-Dawley rats were
      subjected to spinal contusion using a weight-drop injury approach. Western
      blotting and immunofluorescence assays were used to observe the change of ASIC1a
      expression after SCI. The TUNEL staining in vivo as well as the cell viability
      and death assays in spinal neuronal culture were employed to assess the role of
      ASIC1a in the secondary spinal neuronal injury. The electrophysiological
      recording and Ca(2+) imaging were performed to reveal the possible underlying
      mechanism. The antagonists and antisense oligonucleotide for ASIC1a, lesion
      volume assessment assay and behavior test were used to estimate the therapeutic
      effect of ASIC1a on SCI. RESULTS: We show that ASIC1a expression is markedly
      increased in the peri-injury zone after traumatic SCI. Consistent with the change
      of ASIC1a expression in injured spinal neurons, both ASIC1a-mediated whole-cell
      currents and ASIC1a-mediated Ca(2+) entry are significantly enhanced after
      injury. We also show that increased activity of ASIC1a contributes to SCI-induced
      neuronal death. Importantly, our results indicate that down-regulation of ASIC1a
      by antagonists or antisense oligonucleotide reduces tissue damage and promotes
      the recovery of neurological function after SCI. CONCLUSION: This study reveals a
      cellular and molecular mechanism by which ASIC1a is involved in the secondary
      damage process after traumatic SCI. Our results suggest that blockade of Ca(2+) 
      permeable ASIC1a may be a potential neuroprotection strategy for the treatment of
      SCI patients.

PMID- 21725233
TI  - Institutional variation in the surgical treatment of breast cancer: a study of
      the NCCN.
AB  - OBJECTIVE: To investigate the relationship between supply of subspecialty care
      and type of procedure preferentially performed for early stage breast cancer.
      BACKGROUND: Three surgical options exist for early stage breast cancer: (1)
      breast conserving surgery (BCS), (2) mastectomy with reconstruction (RECON), and
      (3) mastectomy alone. Current guidelines recommend that surgical treatment
      decisions should be based on patient preference if a patient is eligible for all
      3. However, studies demonstrate persistent variation in the use of BCS and RECON.
      METHODS: Patients undergoing an operation for DCIS or stage I or II breast cancer
      at NCCN institutions between 2000 and 2006 were identified. Institutional
      procedure rates were determined. Spearman correlations measured the association
      between procedure types. Patient-level logistic regression models investigated
      predictors of procedure type and association with institutional supply of
      subspecialty care. RESULTS: Among 10,607 patients, 19% had mastectomy alone, 60%
      BCS, and 21% RECON. The institutional rate of BCS and RECON were strongly
      correlated (r = -0.80, P = 0.02). Institution was more important than all patient
      factors except age in predicting receipt of RECON or BCS. RECON was more likely
      for patients treated at an institution with a greater supply of reconstructive
      surgeons or where patients live further from radiation facilities. RECON was less
      likely at institutions with longer waiting times for surgery with reconstruction.
      CONCLUSIONS: Even within the NCCN, a consortium of multidisciplinary cancer
      centers, the use of BCS and mastectomy with reconstruction substantially varies
      by institution and correlates with the supply of subspecialty care.

PMID- 21725234
TI  - Dose pattern and effectiveness of paliperidone extended-release tablets in
      patients with schizophrenia.
AB  - OBJECTIVES: The objectives of this 12-week multicenter, open-label,
      noncomparative study were to evaluate the overall effectiveness of paliperidone
      extended release (ER), the feasibility of maintaining patients on the initial
      dose of 6 mg, and the relationship between dose pattern and treatment response in
      schizophrenic patients with inadequate responses to initial treatment in a
      natural setting. METHODS: All patients received 6 mg of paliperidone ER during
      the first 2 weeks, and subsequently, the dose was adjusted at each visit based on
      the patient response. We examined the response rate and the effectiveness of
      different dose patterns of paliperidone ER such as "early increase (dose
      increased to 9 mg at week 2)," "late increase (dose increased to 9 mg at week
      4)," and "maintenance group." RESULTS: The response rate based on the Clinical
      Global Impression of Improvement or Severity response criteria was 33.6% or
      61.7%, respectively. The proportion of patients who stayed with the initial dose
      of 6 mg was 44.5% and the response rate of these patients was 79.8%. When the
      treatment response to the initial dose of 6 mg is inadequate (Clinical Global
      Impression of Improvement >= 4 at week 2), an early increase in the dose seems to
      be more effective than maintenance or late increase of the initial dose.
      CONCLUSIONS: This study suggests that paliperidone ER may be an effective and
      well-tolerated antipsychotics in the treatment of patients with schizophrenia.

PMID- 21725235
TI  - A simple classification model for hospital mortality in patients with acute lung
      injury managed with lung protective ventilation.
AB  - OBJECTIVE: Despite improvements in the care of critically ill patients, hospital
      mortality rate for acute lung injury remains high at approximately 40%. We
      developed a classification rule to stratify mechanically ventilated patients with
      acute lung injury according to hospital mortality and compared this rule with the
      Acute Physiology and Chronic Health Evaluation III prediction. PATIENTS: We used
      data of 2,022 participants in Acute Respiratory Distress Syndrome Network trials
      to build a classification rule based on 54 variables collected before
      randomization. DESIGN: We used a classification tree approach to stratify
      patients according to hospital mortality using a training subset of 1800
      participants and estimated expected prediction errors using tenfold
      crossvalidation. We validated our classification tree using a subset of 222
      participants not included in model building and calculated areas under the
      receiver operating characteristic curves. MEASUREMENTS AND MAIN RESULTS: We
      identified combinations of age (>63 yrs), blood urea nitrogen (>15 mg/dL), shock,
      respiratory rate (>21 breaths/min), and minute ventilation (>13.9 L/min) as
      important predictors of hospital mortality at 90 days. The classification tree
      had a similar expected prediction error in the training set (28% vs. 26%; p =
      .18) and areas under the receiver operating characteristic curve in the
      validation set (0.71 vs. 0.73; p = .71) as did a model based on Acute Physiology
      and Chronic Health Evaluation III. CONCLUSIONS: Our tree-based classification
      rule performed similarly to Acute Physiology and Chronic Health Evaluation III in
      stratifying patients according to hospital mortality, is simpler to use, contains
      risk factors that may be specific to acute lung injury, and identified minute
      ventilation as a potential novel predictor of death in patients with acute lung
      injury.

PMID- 21725236
TI  - Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves
      resuscitation rates after prolonged untreated cardiac arrest in two porcine
      models.
AB  - OBJECTIVE: Sodium nitroprusside-enhanced cardiopulmonary resuscitation consists
      of active compression-decompression, an impedance threshold device, abdominal
      binding, and large intravenous doses of sodium nitroprusside. We hypothesize that
      sodium nitroprusside-enhanced cardiopulmonary resuscitation will significantly
      increase carotid blood flow and return of spontaneous circulation compared to
      standard cardiopulmonary resuscitation after prolonged ventricular fibrillation
      and pulseless electrical activity cardiac arrest. DESIGN: Prospective randomized
      animal study. SETTING: Hennepin County Medical Center Animal Laboratory.
      SUBJECTS: Forty Yorkshire female farm-bred pigs weighing 32 +/- 2 kg.
      INTERVENTIONS: In protocol A, 24 isoflurane-anesthetized pigs underwent 15 mins
      of untreated ventricular fibrillation and were subsequently randomized to receive
      standard cardiopulmonary resuscitation (n = 6), active compression-decompression
      cardiopulmonary resuscitation + impedance threshold device (n = 6), or sodium
      nitroprusside-enhanced cardiopulmonary resuscitation (n = 12) for up to 15 mins.
      First defibrillation was attempted at minute 6 of cardiopulmonary resuscitation.
      In protocol B, a separate group of 16 pigs underwent 10 mins of untreated
      ventricular fibrillation followed by 3 mins of chest compression only
      cardiopulmonary resuscitation followed by countershock-induced pulseless
      electrical activity, after which animals were randomized to standard
      cardiopulmonary resuscitation (n = 8) or sodium nitroprusside-enhanced
      cardiopulmonary resuscitation (n = 8). MEASUREMENTS AND MAIN RESULTS: The primary
      end point was carotid blood flow during cardiopulmonary resuscitation and return
      of spontaneous circulation. Secondary end points included end-tidal CO2 as well
      as coronary and cerebral perfusion pressure. After prolonged untreated
      ventricular fibrillation, sodium nitroprusside-enhanced cardiopulmonary
      resuscitation demonstrated superior rates of return of spontaneous circulation
      when compared to standard cardiopulmonary resuscitation and active compression
      decompression cardiopulmonary resuscitation + impedance threshold device (12 of
      12, 0 of 6, and 0 of 6 respectively, p < .01). In animals with pulseless
      electrical activity, sodium nitroprusside-enhanced cardiopulmonary resuscitation
      increased return of spontaneous circulation rates when compared to standard
      cardiopulmonary resuscitation. In both groups, carotid blood flow, coronary
      perfusion pressure, cerebral perfusion pressure, and end-tidal CO2 were increased
      with sodium nitroprusside-enhanced cardiopulmonary resuscitation. CONCLUSIONS: In
      pigs, sodium nitroprusside-enhanced cardiopulmonary resuscitation significantly
      increased return of spontaneous circulation rates, as well as carotid blood flow
      and end-tidal CO2, when compared to standard cardiopulmonary resuscitation or
      active compression-decompression cardiopulmonary resuscitation + impedance
      threshold device.

PMID- 21725237
TI  - Human umbilical cord blood mesenchymal stem cells protect mice brain after
      trauma.
AB  - OBJECTIVE: To investigate whether human umbilical cord blood mesenchymal stem
      cells, a novel source of progenitors with multilineage potential: 1) decrease
      traumatic brain injury sequelae and restore brain function; 2) are able to
      survive and home to the lesioned region; and 3) induce relevant changes in the
      environment in which they are infused. DESIGN: Prospective experimental study.
      SETTING: Research laboratory. SUBJECTS: Male C57Bl/6 mice. INTERVENTIONS: Mice
      were subjected to controlled cortical impact/sham brain injury. At 24 hrs
      postinjury, human umbilical cord blood mesenchymal stem cells (150,000/5 MUL) or
      phosphate-buffered saline (control group) were infused intracerebroventricularly
      contralateral to the injured side. Immunosuppression was achieved by cyclosporine
      A (10 mg/kg intraperitoneally). MEASUREMENTS AND MAIN RESULTS: After controlled
      cortical impact, human umbilical cord blood mesenchymal stem cell transplantation
      induced an early and long-lasting improvement in sensorimotor functions assessed
      by neuroscore and beam walk tests. One month postinjury, human umbilical cord
      blood mesenchymal stem cell mice showed attenuated learning dysfunction at the
      Morris water maze and reduced contusion volume compared with controls. Hoechst
      positive human umbilical cord blood mesenchymal stem cells homed to lesioned
      tissue as early as 1 wk after injury in 67% of mice and survived in the injured
      brain up to 5 wks. By 3 days postinjury, cell infusion significantly increased
      brain-derived neurotrophic factor concentration into the lesioned tissue,
      restoring its expression close to the levels observed in sham operated mice. By 7
      days postinjury, controlled cortical impact human umbilical cord blood
      mesenchymal stem cell mice showed a nonphagocytic activation of
      microglia/macrophages as shown by a selective rise (260%) in CD11b staining (a
      marker of microglia/macrophage activation/recruitment) associated with a decrease
      (58%) in CD68 (a marker of active phagocytosis). Thirty-five days postinjury,
      controlled cortical impact human umbilical cord blood mesenchymal stem cell mice
      showed a decrease of glial fibrillary acidic protein positivity in the scar
      region compared with control mice. CONCLUSIONS: These findings indicate that
      human umbilical cord blood mesenchymal stem cells stimulate the injured brain and
      evoke trophic events, microglia/macrophage phenotypical switch, and glial scar
      inhibitory effects that remodel the brain and lead to significant improvement of
      neurologic outcome.

PMID- 21725238
TI  - Association of prehospitalization aspirin therapy and acute lung injury: results
      of a multicenter international observational study of at-risk patients.
AB  - OBJECTIVE: To evaluate the association between prehospitalization aspirin therapy
      and incident acute lung injury in a heterogeneous cohort of at-risk medical
      patients. DESIGN: This is a secondary analysis of a prospective multicenter
      international cohort investigation. SETTING: Multicenter observational study
      including 20 US hospitals and two hospitals in Turkey. PATIENTS: Consecutive,
      adult, nonsurgical patients admitted to the hospital with at least one major risk
      factor for acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Baseline characteristics and acute lung injury risk factors/modifiers were
      identified. The presence of aspirin therapy and the propensity to receive this
      therapy were determined. The primary outcome was acute lung injury during
      hospitalization. Secondary outcomes included intensive care unit and hospital
      mortality and intensive care unit and hospital length of stay. Twenty-two
      hospitals enrolled 3855 at-risk patients over a 6-month period. Nine hundred
      seventy-six (25.3%) were receiving aspirin at the time of hospitalization. Two
      hundred forty (6.2%) patients developed acute lung injury. Univariate analysis
      noted a reduced incidence of acute lung injury in those receiving aspirin therapy
      (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.90; p = .010). This
      association was attenuated in a stratified analysis based on deciles of aspirin
      propensity scores (Cochran-Mantel-Haenszel pooled OR, 0.70; 95% CI, 0.48-1.03; p
      = .072). CONCLUSIONS: After adjusting for the propensity to receive aspirin
      therapy, no statistically significant associations between prehospitalization
      aspirin therapy and acute lung injury were identified; however, a prospective
      clinical trial to further evaluate this association appears warranted.

PMID- 21725239
TI  - Effect of pravastatin on the frequency of ventilator-associated pneumonia and on
      intensive care unit mortality: open-label, randomized study.
AB  - OBJECTIVE: To investigate whether the use of pravastatin reduces the frequency of
      ventilator-associated pneumonia and whether it is related to favorable outcomes
      in critical care patients. DESIGN: Two-center, two-arm, randomized, open-label,
      controlled trial. SETTING: University Hospital and General Hospital of Larissa,
      Greece. PATIENTS: Consecutive patients were recruited from the intensive care
      units of the two hospitals. Patient inclusion criteria included mechanical
      ventilation and intensive care unit stay of >48 hrs. INTERVENTIONS: The two arms
      consisted of treatment plus oral pravastatin sodium (40 mg) (n = 71 patients,
      pravastatin group) and treatment without pravastatin (n = 81 patients, control
      group). Treatment was started after randomization and ended 30 days later.
      MEASUREMENTS AND MAIN RESULTS: Ventilator-associated pneumonia frequency and
      intensive care unit mortality at 30 days and at the end of intensive care unit
      stay were measured. Adverse events related to statin treatment in the intensive
      care unit were documented. Sixteen patients (22.5%) in the pravastatin group and
      28 (34.5%) in the control group (p = .11) presented pneumonia during the 30-day
      treatment period in the intensive care unit. There was an indication for
      increased probability of being free from ventilator-associated pneumonia during
      the 30-day treatment period in the pravastatin group compared to the control
      group (p = .06) and significantly increased probability during the whole
      intensive care unit period of stay (p = .04) in the pravastatin group compared to
      the control group in the subgroup of patients with Acute Physiology and Chronic
      Health Evaluation scores of >= 15. Six patients (8.45%) in the pravastatin group
      and 16 (19.85%) in the control group died during the 30-day treatment period (p =
      .06), whereas 10 (14.1%) patients in the pravastatin group and 24 (29.1%)
      patients in the control group died during the whole period of intensive care unit
      stay (p = .03). Pravastatin group patients with Acute Physiology and Chronic
      Health Evaluation scores of >= 15 had significantly increased probability of
      survival compared to controls during the 30-day treatment period (p = .04).
      Creatine kinase and hepatic function enzyme levels during the whole study period
      were not significantly different between the pravastatin group and control group.
      CONCLUSION: This study provides evidence that pravastatin may favorably affect
      the outcome of critical care patients.

PMID- 21725240
TI  - Amyotrophic lateral sclerosis: an update.
AB  - PURPOSE OF REVIEW: The aim is to review recent publications on amyotrophic
      lateral sclerosis (ALS). RECENT FINDINGS: The Awaji recommendations for
      electrophysiological diagnosis will permit earlier clinical trials entry. The use
      of ultrasound to visualize fasciculations, even in deep muscles, will contribute
      to earlier diagnosis, as well. Unfortunately, recent clinical trials in ALS have
      been disappointing, as illustrated by the negative lithium trials. New, less
      expensive, trial designs and the inclusion of patients early in the course of ALS
      are positive approaches for future trials. The search for ALS biomarkers
      continues and a number of encouraging reports have been published, but no
      features unique to ALS have yet transformed this field. The most exciting
      advances in ALS arise from protein studies and genetics. Recognition that the
      ubiquitinated cytosolic inclusions in sporadic ALS, as well as in some patients
      with frontotemporal dementia (FTD), contain TDP-43, and that some familial cases
      (and a few sporadic cases) have mutations of the TDP-43 gene has transformed
      previous concepts on ALS pathogenesis. Other newly recognized mutations linked to
      ALS, such as fused-in-sarcoma (FUS) and valosin-containing protein (VCP), have
      not only widened the spectrum of genes involved in ALS but also consolidated the
      close relation between ALS and FTD. SUMMARY: ALS research is entering a new phase
      that should generate new proposals regarding putative therapies, or strategies
      for disease treatment. A continuing difficulty, however, is early clinical
      diagnosis and, especially, the need for identification of a unique biomarker,
      sensitive to clinical change in the course of the disease.

PMID- 21725241
TI  - The prominent role of stimulus processing: cholinergic function and dysfunction
      in cognition.
AB  - PURPOSE OF REVIEW: The present review develops a framework from which to
      understand the role of the cholinergic system in healthy cognition and in
      cognitive dysfunction. Traditionally, the cholinergic system has been thought to
      have direct influence on cognitive processes such as working memory and
      attention. Although the influence of cholinergic function on stimulus processing
      has been long appreciated, the notion that cholinergic effects on stimulus
      processing is the mechanism by which acetylcholine influences cognitive processes
      has only more recently been considered. RECENT FINDINGS: Literature supporting
      the hypothesis that cholinergic modulation influences cognitive functions through
      stimulus processing mechanisms has been growing for over a decade. Recent
      conceptualizations of the developing literature have argued for a new
      interpretation to an old and developing literature. SUMMARY: The argument that
      cholinergic function modulates cognitive processes by direct effects on basic
      stimulus processing extends to cognitive dysfunction in neuropathological
      conditions including dementia and mood disorders. Memory and attention deficits
      observed in these and other conditions can be understood by evaluating the impact
      of cholinergic dysfunction on stimulus processing, rather than on the cognitive
      function in general.

PMID- 21725242
TI  - Impulse control disorders in Parkinson's disease: recent advances.
AB  - PURPOSE OF REVIEW: The aim is to review the recent advances in the epidemiology
      and pathophysiology of impulse control disorders (ICDs) in Parkinson's disease.
      RECENT FINDINGS: Large cross-sectional and case-control multicentre studies show
      that ICDs in Parkinson's disease are common, with a frequency of 13.6%. These
      behaviours are associated with impaired functioning and with depressive, anxiety
      and obsessive symptoms, novelty seeking and impulsivity. Behavioural subtypes
      demonstrate differences in novelty seeking and impulsivity, suggesting
      pathophysiological differences. Observational and neurophysiological studies
      point towards a potential mechanistic overlap between behavioural (ICDs) and
      motor (dyskinesias) dopaminergic sequelae. Converging data suggest dopamine
      agonists in ICDs appear to enhance learning from rewarding outcomes and impulsive
      choice. ICD patients also have enhanced risk preference and impaired working
      memory. Neuroimaging data point towards enhanced bottom-up ventral striatal
      dopamine release to incentive cues, gambling tasks and reward prediction, and
      possible inhibition of top-down orbitofrontal influences. Dopamine agonist
      related ventral striatal hypoactivity to risk is consistent with impaired risk
      evaluation. SUMMARY: Recent large-scale studies and converging findings are
      beginning to provide an understanding of mechanisms underlying ICDs in
      Parkinson's disease, which can guide prevention of these behaviours and optimize
      therapeutic approaches.

PMID- 21725243
TI  - Are we undertreating invasive bladder cancer? Optimizing outcomes in a high-risk
      disease.
AB  - PURPOSE OF REVIEW: To highlight the important issues that may improve patient
      outcomes in the setting of invasive bladder cancer. RECENT FINDINGS: Although
      approximately 80% of patients with bladder cancer present with disease confined
      to the mucosa which can be treated locally, progression to muscle-invasive
      bladder carcinoma (MIBC) is associated with adverse outcomes. Stage and grade
      have traditionally been used to predict progression. European Organization for
      Research and Treatment of Cancer (EORTC) and Club Urologico Espanol de
      Tratamiento Oncologico (CUETO) have designed prognostic models that further
      refine risk assessment. Recent attempts to integrate molecular biomarkers may
      further improve these models. Treating appropriate patients earlier with radical
      cystectomy offers the hope of decreasing the extent of disease at the time of
      surgery. In patients with MIBC, neoadjuvant chemotherapy has been shown to
      improve patient outcome. Selecting appropriate patients remains a challenge.
      Preoperative models to predict risk of lymph node-positive disease and
      preoperative imaging with fluorodeoxyglucose positron emission tomography or MRI
      have been shown to be useful in that regard. Multidisciplinary care offers better
      patient support and collaboration during the treatment phase and improves quality
      of life. SUMMARY: Improved outcomes in localized bladder cancer requires an
      integrated approach including better identification of high-risk disease, earlier
      use of cystectomy, broader use of chemotherapy and the availability of a
      dedicated multidisciplinary team.

PMID- 21725244
TI  - Current systemic management of metastatic renal cell carcinoma - first line and
      second line therapy.
AB  - PURPOSE OF REVIEW: The improved understanding of the complex biochemical and
      genetic pathways associated with renal-cell carcinoma (RCC) has led to rapid
      development of novel targeted therapies over the last decade. The aim of this
      review is to present and discuss the most recent clinical trial data that support
      the currently approved first and second line agents in the treatment of
      metastatic renal cell carcinoma (mRCC). New directions in treatment will also be
      explored. RECENT FINDINGS: The currently approved first and second line agents
      for the treatment of mRCC include sunitinib, pazopanib, sorafenib, bevacizumab,
      temsirolimus, and everolimus. Each of these new agents has shown meaningful
      clinical benefit in phase III trials and as a group they have replaced cytokines
      as the frontline therapy for advanced and mRCC. Several new agents are currently
      being evaluated in phase II and III studies that may provide further benefit in
      the future. SUMMARY: The treatment paradigm for mRCC had drastically changed over
      the last decade bringing new hope for improved outcomes and ongoing advances. In
      spite of recent headway, mRCC remains a disease with no curative therapy and more
      effective treatment options are needed.

PMID- 21725245
TI  - Malignant extradural spinal cord compression in men with prostate cancer.
AB  - PURPOSE OF REVIEW: Malignant epidural spinal cord compression (MESCC) is a
      dreaded complication of malignancy and is fortunately not common. Approximately
      7% of men dying of prostate cancer will have at least one episode of MESCC during
      their lifetime. Treatment needs to be individualized and estimating the prognosis
      is critical to achieving a balance between effectiveness therapy and the burden
      of treatment. RECENT FINDINGS: A consortium of multiple centers has defined
      prognosis scales, and multiple randomized studies have helped define the optimal
      dose fractionation schedule for patients getting radiotherapy. SUMMARY: Simple
      prognosis scales available to assist the clinician are reviewed. For poor
      prognosis patients, a single fraction of 8  Gy is just as effective as multiple
      fractions, however, are much more convenient. For good prognosis patients,
      surgery and radiation should be considered. For patients not getting surgery,
      enrollment in clinical trials of single vs. multiple fractions of radiation
      should be a priority. For high-risk patients, screening strategies are being
      developed and hold promise for maintaining ambulation throughout the patients'
      lifetime.

PMID- 21725246
TI  - Patients enrolled in HIV care in Mozambique: baseline characteristics and follow
      up outcomes.
AB  - OBJECTIVE: To utilize routinely collected service delivery data from HIV care and
      treatment clinics in Mozambique to describe the patient population and
      programmatic outcomes from 2003 to 2009. METHODS: Data from patient charts were
      entered into an electronic database at 28 clinics in 5 Mozambican provinces.
      Patients' characteristics at enrollment in HIV care and at antiretroviral therapy
      (ART) initiation were examined. We calculated a corrected 12-month mortality
      estimate using a recently developed nomogram for sub-Saharan African ART
      patients. RESULTS: A total of 154,188 HIV-infected individuals (10,164 children
      <15 years old) were enrolled in HIV care services between 2003 and 2009. Of the
      51,269 (36%) adults who started ART, 35% initiated ART with CD4 count <100 cells
      per microliter and 14.4% with World Health Organization stage IV. Just more than
      10% (10.5%) of women were documented to be pregnant at enrollment. One-third of
      the 3,745 (37%) children who initiated ART were <2 years old, and 53% of those <5
      years initiated ART severely immunosuppressed (CD4% <15%). Thirty-five percent of
      all children and 30% of those initiating ART met the definition of severe
      malnourishment (weight-for-age Z score <-3). Among those who initiated ART, the
      median estimated 12-month mortality rate across sites was 13.1% (interquartile
      range: 11.5%-16.0%) and 13.5% (interquartile range: 11.4%-17.4%) for adults and
      children, respectively. CONCLUSIONS: A substantial number of HIV-infected
      patients have been enrolled in HIV care and initiated on ART, with many patients
      having advanced HIV disease. With the release of new guidelines for ART use for
      adults, pregnant women, and children, extensive efforts are needed to ensure more
      timely initiation of ART.

PMID- 21725247
TI  - Exploring the relative costs of contact tracing for increasing HIV case finding
      in sub-Saharan countries.
AB  - BACKGROUND: Contact tracing (CT) has rarely been used to improve HIV case finding
      in sub-Saharan Africa because of concerns regarding privacy protection and
      possibly high costs. METHODS: We estimate the relative cost of identifying an
      undiagnosed HIV infection through CT compared with client-initiated voluntary
      counseling and testing (VCT) and door-to-door provider-initiated testing (PIT).
      We used data from the Likoma Network Study, a study of sexual networks and HIV
      infection conducted on the small island of Likoma in northern Malawi, to inform
      these calculations. RESULTS: In Likoma, the probability that partners of HIV
      index cases could be traced and that they would consent to HIV testing and
      counseling was high and varied by partner type. HIV prevalence ranged from 48.1%
      to 66.7% among the partners who were tested. Per newly diagnosed infection, CT is
      rarely a cheaper case finding approach than VCT in populations with HIV
      prevalence > 5%. In populations with HIV prevalence < 5%, CT is an attractive
      case-finding approach relative to VCT when few HIV-infected individuals are aware
      of their status. Compared with door-to-door PIT, CT is almost always preferred
      when the population prevalence is below 10%, unless CT costs are prohibitively
      high. When HIV prevalence is >10%, providing CT for current spouses of index
      cases remains an attractive approach to HIV case finding. CONCLUSIONS: CT could
      complement client-initiated VCT or door-to-door PIT in a large number of sub
      Saharan populations affected by generalized epidemics of varying magnitudes.

PMID- 21725248
TI  - Drug resistance profiles among HIV-1-infected children experiencing delayed
      switch and 12-month efficacy after using second-line antiretroviral therapy: an
      observational cohort study in rural China.
AB  - OBJECTIVE: To analyze the genotypic resistance profiles of HIV-infected children
      from rural China who were experiencing virologic failure to first-line
      antiretroviral therapy regimens and to evaluate 1-year regimen efficacy after
      switching to second-line therapy. METHODS: A prospective cohort study was
      performed. Seventy-six children from the first rural pilot program with HIV viral
      load >1000 copies per milliliter on 2 consecutive occasions were studied. We
      analyzed genotype results and observed second-line therapy efficacy to 12 months.
      RESULTS: After 33.1 (23.3, 41.1) months on first-line treatment after enrollment
      into national program, 98.7% of genotyped patients developed high-level
      resistance to nevirapine and 81.6% of patients had high-level resistance to
      efavirenz. High-level resistance to lamivudine was observed in 82.9%, followed by
      57.9% for stavudine and 52.6% for zidovudine. In the nonnucleoside reverse
      transcriptase inhibitor class, the most common mutations were K103N/S at 50% and
      Y181C/I at 48.7%. M184V/I was the most common nucleoside reverse transcriptase
      inhibitor resistance mutation at 77.6%, the mutation rate for >=3 thymidine
      analogue mutations, Q151M, and K65R were 33%, 12%, and 9%, respectively. After 12
      months of boosted protease inhibitor-based second-line therapy, CD4 counts had on
      average increased 256 cells per cubic millimeter compared with switch baseline
      and 83.1% of patients had undetectable viral loads (<50 copies/mL). CONCLUSIONS:
      HIV-1-infected children who continued their first-line regimen regardless of
      virologic failure harbored multiple resistance mutations. Although the extent of
      resistance to nucleoside reverse transcriptase inhibitor class drugs would be
      expected to limit subsequent treatment options, the current second-line regimen
      remained effective during a 1-year observational period.

PMID- 21725249
TI  - Couple-based HIV prevention for low-income drug users from New York City: a
      randomized controlled trial to reduce dual risks.
AB  - OBJECTIVE: Dual threats of injection drug use and risky sexual practices continue
      to increase transmission of HIV and other sexually transmitted Infections (STIs)
      among drug-using couples in low-income communities in the United States. Two
      hypotheses were tested: (1) "intervention effect"-whether the HIV risk-reduction
      intervention provided to the couple or individual partners would be more
      efficacious in decreasing number of unprotected sexual acts and having a lower
      cumulative incidence of biologically confirmed STIs over the 12-month follow-up
      period compared with the attention control condition; and (2) "modality effect"
      whether the HIV risk-reduction intervention would be more likely to decrease the
      number of unprotected sexual acts and have a lower cumulative STI incidence when
      delivered to a couple compared with the same intervention delivered to an
      individual. DESIGN: Using a randomized controlled trial, 282 HIV-negative drug
      using couples (564 individuals) were randomly assigned to receive either of the
      following: (1) couple-based risk reduction; (2) individual-based HIV risk
      reduction, or (3) couple-based wellness promotion, which served as an attention
      control condition. RESULTS: Over 12-month follow-up, there was a 30% reduction in
      the incidence rate of unprotected acts of intercourse with the study partners
      compared with participants in the attention control arm. Moreover, over 12-month
      follow-up there was a 29% reduction in the same outcome in the couple arm
      compared with the individual arm with a 41% reduction at the 12-month follow-up.
      CONCLUSION: A couple-based approach that addresses drug and sexual risks and
      targets low-income active drug users may help curb the HIV epidemic.

PMID- 21725250
TI  - Neurocognitive impact of substance use in HIV infection.
AB  - BACKGROUND: : To determine how serious a confound substance use (SU) might be in
      studies on HIV-associated neurocognitive disorder (HAND), we examined the
      relationship of SU history to neurocognitive impairment (NCI) in participants
      enrolled in the Central Nervous System HIV Antiretroviral Therapy Effects
      Research study. METHODS: : After excluding cases with behavioral evidence of
      acute intoxication and histories of factors that independently could account for
      NCI (eg, stroke), baseline demographic, medical, SU, and neurocognitive data were
      analyzed from 399 participants. Potential SU risk for NCI was determined by the
      following criteria: lifetime SU Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition diagnosis, self-report of marked lifetime SU, or
      positive urine toxicology. Participants were divided into 3 groups as follows: no
      SU (n = 134), nonsyndromic SU (n = 131), syndromic SU (n = 134) and matched on
      literacy level, nadir CD4, and depressive symptoms. RESULTS: : Although
      approximately 50% of the participants were diagnosed with HAND, a multivariate
      analysis of covariance of neurocogntive summary scores, covarying for urine
      toxicology, revealed no significant effect of SU status. Correlational analyses
      indicated weak associations between lifetime heroin dosage and poor recall and
      working memory and between cannabis and cocaine use and better verbal fluency.
      CONCLUSIONS: : These data indicate that HIV neurocognitive effects are seen at
      about the same frequency in those with and without historic substance abuse in
      cases that are equated on other factors that might contribute to NCI. Therefore,
      studies on neuroAIDS and its treatment need not exclude such cases. However, the
      effects of acute SU and current SU disorders on HAND require further study.

PMID- 21725251
TI  - RAD51 and XRCC3 gene polymorphisms and the risk of developing acute myeloid
      leukemia.
AB  - RAD51 (Rec A homolog of E. coli) is a polymorphic gene and one of the central
      proteins in homologous recombination-DNA-double-stand breaks (HR-DNA-DSB) repair
      pathway, which is vital in maintaining genetic stability within a cell. The x-ray
      repair cross complementing (XRCC3) protein also functions in HR-DNA-DSB repair
      pathway and directly interacts with and stabilizes RAD51 and the closely related
      RAD51C. The aim of this study was to determine the prevalence of the RAD51 and
      XRCC3 repair gene polymorphisms among acute myeloid leukemia (AML) patients and
      to define their role in development of AML and its correlation with the clinical
      presentation, laboratory data as well as treatment outcome using polymerase chain
      reaction-restriction fragment length polymorphism assay in 50 de novo AML
      patients as well as 30 healthy subjects as a control group. Our study revealed
      that RAD51 G135C and XRCC3 Thr241Met alleles were associated with increased risk
      of AML with odds ratio (OR) of 2.833 and 2.909 and 95% confidence interval (CI)
      of 1.527 to 8.983 and 1.761 to 9.788, respectively. Moreover, when combining the
      2 genes polymorphisms, a significant elevation of the risk of AML was found with
      OR of 3.124 and 95% CI of 1.872 to 11.243. As regards treatment outcome, a highly
      statistical significant difference was found between XRCC3 genotypes with P value
      of 0.001, whereas no significant difference was present between RAD51 genotypes
      with P value of 0.29. This clarifies that XRCC3 gene polymorphisms was found to
      have a significant impact on the risk of treatment failure with OR of 3.560 and
      95% CI of 1.167 to 10.875; however, RAD51 gene polymorphism was not found to have
      an equivalent effect with OR of 2.813 and 95% CI of 0.933 to 10.828. So XRCC3
      gene polymorphism might be considered as a prognostic marker in AML. In
      conclusion, RAD51 and XRCC3 genes polymorphisms may play an important role in the
      development of AML.

PMID- 21725252
TI  - Primary vertebral tumors: a review of epidemiologic, histological, and imaging
      findings, Part I: benign tumors.
AB  - Primary vertebral tumors, although less common than metastases to the spine, make
      up a heterogeneous group of neoplasms that can pose diagnostic and treatment
      challenges. They affect both the adult and the pediatric population and may be
      benign, locally aggressive, or malignant. An understanding of typical imaging
      findings will aid in accurate diagnosis and help neurosurgeons appreciate
      anatomic subtleties that may increase their effective resection. An understanding
      of the histological similarities and differences between these tumors is
      imperative for all members of the clinical team caring for these patients. In
      this first review of 2 parts, we discuss the epidemiological, histological, and
      imaging features of the most common benign primary vertebral tumors-aneurysmal
      bone cyst, chondroma and enchondroma, hemangioma, osteoid osteoma, and
      osteoblastoma-and lesions related to eosinophilic granuloma and fibrous
      dysplasia. In addition, we discuss the basic management paradigms for each of
      these diagnoses. In combination with part II of the review, which focuses on
      locally aggressive and malignant tumors, this article provides a comprehensive
      review of primary vertebral tumors.

PMID- 21725253
TI  - Accuracy of frame-based stereotactic magnetic resonance imaging vs frame-based
      stereotactic head computed tomography fused with recent magnetic resonance
      imaging for postimplantation deep brain stimulator lead localization.
AB  - BACKGROUND: Introduction of the portable intraoperative CT scanner provides for a
      precise and cost-effective way of fusing head CT images with high-tesla MRI for
      the exquisite definition of soft tissue needed for stereotactic targeting.
      OBJECTIVE: To evaluate the accuracy of stereotactic electrode placement in
      patients undergoing deep brain stimulation (DBS) by comparing frame-based
      postimplantation intraoperative CT (iCT) images fused to a recent 3T-MRI with
      frame-based postimplantation intraoperative MRI (iMRI) alone. METHODS: Frame
      based DBS surgeries of 46 targets performed from February 8, 2007 to April 28,
      2008 in 26 patients with the use of immediate postimplantation iMRI for target
      localization were compared with frame-based immediate postimplantation iCT fused
      with a recent 3T brain MRI for DBS localization of 50 targets performed from
      August 13, 2008 to February 18, 2010 in 26 patients. Pre- and postoperative mid
      anterior commissure-posterior commissure line coordinates and XYZ coordinates for
      preoperatively calculated DBS targets (intended target) and for the permanent DBS
      lead tips were determined. The differences between preoperative DBS target and
      postoperative permanent DBS lead-tip coordinates based on postimplantation
      intraoperative MRI for the MRI-alone group and based on postimplantation
      intraoperative CT fused to recent preoperative MRI in the CT-MRI group were
      measured. The t test and Yuen test were used for comparison. RESULTS: No
      statistically significant differences were found between the 2 groups when
      comparing the pre- and postperative changes in mid anterior commissure-posterior
      commissure line coordinates and XYZ coordinates. CONCLUSION: Postimplantation DBS
      lead localization and therefore targeting accuracy was not significantly
      different between frame-based stereotactic 1.5T-MRI and frame-based stereotactic
      head CT fused with recent 3T-MRI.

PMID- 21725254
TI  - Pedunculopontine nucleus stimulation improves gait freezing in Parkinson disease.
AB  - BACKGROUND: Pedunculopontine nucleus (PPN) stimulation is a novel therapy for
      Parkinson disease. However, controversies remain regarding the clinical
      application of this new therapy, including patient selection, electrode
      positioning, and how best to assess outcomes. OBJECTIVE: To clarify the clinical
      application of PPN stimulation in Parkinson disease. METHODS: Five consecutive
      patients with Parkinson disease complicated by severe gait freezing, postural
      instability, and frequent falls (all persisting even while the patient was on
      medication) received bilateral stimulation of the mid-lower PPN without
      costimulation of other brain targets. Outcomes were assessed prospectively over 2
      years with gait-specific questionnaires and the Unified Parkinson Disease Rating
      Scale (part III). RESULTS: The primary outcome, the Gait and Falls Questionnaire
      score, improved significantly with stimulation. Benefits were maintained over 2
      years. Unified Parkinson Disease Rating Scale (part III) items assessing gait and
      posture were relatively insensitive to these treatment effects. Beneficial
      effects often appeared to outlast stimulation for hours or longer. Thus, single
      session on- vs off-stimulation assessments may be susceptible to "delayed washout
      effects." Stimulation of the PPN did not change akinesia scores or dopaminergic
      medication requirements. CONCLUSION: Bilateral stimulation of the mid-lower PPN
      (more caudal than previous reports) without costimulation of other brain targets
      may be beneficial for the subgroup of patients with Parkinson disease who
      experience severe gait freezing and postural instability with frequent falls,
      which persist even while on medication. Choosing appropriate outcome measures and
      accounting for the possibility of prolonged stimulation washout effects appear to
      be important for detecting the clinical benefits.

PMID- 21725255
TI  - Can we predict the efficacy of the semont maneuver in the treatment of benign
      paroxysmal positional vertigo of the posterior semicircular canal?
AB  - OBJECTIVE: To establish success- or failure-predicting factors in Semont maneuver
      in the treatment of benign paroxysmal positional vertigo. STUDY DESIGN:
      Prospective study. SETTING: Referral center, institutional practice, ambulatory
      care (outpatient clinic). PATIENTS: A consecutive sample of 135 patients
      diagnosed with unilateral benign paroxysmal positional vertigo of posterior
      semicircular canal for 3 years (September 2007 to August 2010). INTERVENTION:
      Semont maneuver. MAIN OUTCOME MEASURES: Duration of the latency period and
      nystagmus status with the Dix-Hallpike test. Presence or absence of orthotropic
      nystagmus in the second position of the Semont maneuver. Effectiveness of the
      Semont maneuver (cure versus no cure). RESULTS: The Semont maneuver is effective
      in 73% of the patients. Orthotropic nystagmus was present in 67% of the cases and
      absent in 33%; when we found orthotropic nystagmus, the maneuver was effective in
      81% of the patients, but only in 57% if this nystagmus was not present (Fisher's
      exact test, p = 0.004; odds ratio, 3.308; 95% confidence interval, 1.492-7.334).
      The maneuver's efficacy and the presence of orthotropic nystagmus were not
      affected by the duration of nystagmus status in the Dix-Hallpike test. The
      duration of the latency period had no effect on the maneuver's efficacy, but it
      did affect the appearance of orthotropic nystagmus (Mann-Whitney test, p =
      0.016). CONCLUSION: The presence of orthotropic nystagmus in the second position
      of the Semont maneuver indicates a good prognosis, but its absence does not
      necessarily mean that the maneuver will fail. Orthotropic nystagmus is more
      common in patients with shorter latency periods, suggesting that its appearance
      is related to cupulolithiasis mechanisms.

PMID- 21725256
TI  - Middle fossa decompression for hearing preservation: a review of institutional
      results and indications.
AB  - OBJECTIVE: To assess the duration of hearing preservation from time of vestibular
      schwannoma middle fossa decompression with short-term and 1-year hearing
      preservation rates. STUDY DESIGN: Retrospective case review. SETTING: Tertiary
      referral center. PATIENTS: Patients with and without neurofibromatosis type 2 who
      underwent middle fossa decompression. We excluded patients without tumor size or
      audiograms at initial diagnosis or follow-up less than 3 months. INTERVENTIONS:
      Middle cranial fossa decompression, audiometry, and magnetic resonance imaging.
      MAIN OUTCOME MEASURES: Period of hearing maintenance (from surgery to longest
      time point that preoperative American Academy of Otolaryngology-Head and Neck
      Surgery [AAO-HNS] hearing class maintained or improved), short-term hearing
      preservation (within 3 mo of surgery), and 1-year hearing preservation. RESULTS:
      A total of 49 patients underwent middle fossa decompression of vestibular
      schwannoma. Approximately 90% of patients had documented hearing loss before
      surgery, and more than 50% of patients exhibited significant tumor growth before
      surgery. Of these surgeries, more than 90% were performed in patients with
      hearing loss in an only hearing ear, and more than 90% were patients with
      neurofibromatosis type 2. The mean period of hearing maintenance was 2.1 years.
      The short-term hearing preservation rate as measured by the change from
      preoperative AAO-HNS hearing class was approximately 90%. The 1-year hearing
      preservation rate as measured by change from preoperative AAO-HNS hearing class
      was 63%. CONCLUSION: Middle fossa decompression for vestibular schwannoma can
      prolong hearing in patients with hearing changes in an only hearing ear.
      Understanding the duration of hearing preservation can enable more effective
      counseling of patients considering middle cranial fossa decompression for
      vestibular schwannoma.

PMID- 21725257
TI  - Stability, survival, and tolerability of a novel baha implant system: six-month
      data from a multicenter clinical investigation.
AB  - OBJECTIVE: Determination of the difference in implant stability between a novel
      Baha implant system (test) and the previous-generation implant system (control).
      METHODS: In an open, randomized, prospective multicenter clinical investigation,
      77 adult patients with Baha implants were included. Test and control implants
      were randomly assigned in proportions of 2:1. Implant stability quotient (ISQ)
      values were recorded using resonance frequency analysis at the time of
      implantation and at 10 days, at 4, 6, 8, and 12 weeks, and at 6 months after
      surgery. Skin reactions were evaluated according to the Holgers classification.
      Sound processor fitting was performed from 6 weeks after implantation. RESULTS:
      Significantly higher mean ISQ values, measured between 0 and 6 months, were
      obtained for test compared to control implants (70.4 versus 65.4, p < 0.0001).
      Statistically significant differences were obtained for the study population as a
      whole and for the subgroup of patients loaded at 6 +/- 1 weeks after implant
      surgery (63.6% of patients). Up to 12 weeks, Holgers rates were comparable,
      whereas at 6 months, more skin reactions (Grades 1 and 2) were observed in the
      control implant group. No reduction in mean ISQ values was observed after implant
      loading. CONCLUSION: The test implant showed higher mean ISQ values at the time
      of placement and over time. The level of osseointegration reached with the
      implants in adults as early as 6 weeks after implantation was sufficient to
      support the sound processor. The test implant system is expected to provide
      additional benefits related to the improvement of the degree of osseointegration,
      especially for patients with thin or compromised bone.

PMID- 21725258
TI  - Protective effects of pentoxifylline and nimodipine on acoustic trauma in Guinea
      pig cochlea.
AB  - OBJECTIVE: To examine the protective effects of the vasodilator and
      hemorheologically active drug pentoxifylline and the calcium channel blocker
      nimodipine on the cochlea after acoustic overexposure in guinea pigs. METHODS:
      Eighteen guinea pigs were used. The animals were divided into 5 groups: 1)
      control, 2) acoustic trauma, 3) nimodipine plus acoustic trauma, 4)
      pentoxifylline plus acoustic trauma, and 5) pentoxifylline plus nimodipine plus
      acoustic trauma. Nimodipine was given to the guinea pigs 3 mg/kg
      intraperitoneally in a single dose; pentoxifylline was given 150 mg/kg in a
      single dose intraperitoneally. A gunnery range was used to create acoustic
      trauma. The auditory brainstem response of each guinea pig was determined first;
      then, the animals were killed, and their cochleas were examined under an electron
      microscope. RESULTS: In the acoustic trauma group, negative auditory brainstem
      response potentials were seen as was well-adjusted cellular damage to the organ
      of Corti. In the pentoxifylline group, near-normal auditory brainstem response
      recordings and organ of Corti histologic findings were found. Organ of Corti
      damage was seen in the pentoxifylline plus nimodipine plus acoustic trauma group.
      CONCLUSION: We determined that pentoxifylline was highly protective against
      noise, but nimodipine was not. Also, pentoxifylline and nimodipine, when used
      together, increased damage to the organ of Corti.

PMID- 21725259
TI  - Speech detection in noise and spatial unmasking in children with simultaneous
      versus sequential bilateral cochlear implants.
AB  - OBJECTIVES: To measure speech detection in noise performance for children with
      bilateral cochlear implants (BiCI), to compare performance in children with
      simultaneous implant versus those with sequential implant, and to compare
      performance to normal-hearing children. STUDY DESIGN: Prospective cohort study.
      SETTING: Tertiary academic pediatric center. PATIENTS: Children with early-onset
      bilateral deafness and 2-year BiCI experience, comprising the "sequential" group
      (>2 yr interimplantation delay, n = 12) and "simultaneous group" (no
      interimplantation delay, n = 10) and normal-hearing controls (n = 8).
      INTERVENTION: Thresholds to speech detection (at 0-degree azimuth) were measured
      with noise at 0-degree azimuth or +/- 90-degree azimuth. MAIN OUTCOME MEASURES:
      Spatial unmasking (SU) as the noise condition changed from 0-degree azimuth to +/
      90-degree azimuth and binaural summation advantage (BSA) of 2 over 1 CI.
      RESULTS: Speech detection in noise was significantly poorer than controls for
      both BiCI groups (p < 0.0001). However, the SU in the simultaneous group
      approached levels found in normal controls (7.2 +/- 0.6 versus 8.6 +/- 0.6 dB, p
      > 0.05) and was significantly better than that in the sequential group (3.9 +/-
      0.4 dB, p < 0.05). Spatial unmasking was unaffected by the side of noise
      presentation in the simultaneous group but, in the sequential group, was
      significantly better when noise was moved to the second rather than the first
      implanted ear (4.8 +/- 0.5 versus 3.0 +/- 0.4 dB, p < 0.05). This was consistent
      with a larger BSA from the sequential group's second rather than first CI.
      CONCLUSION: Children with simultaneously implanted BiCI demonstrated an advantage
      over children with sequential implant by using spatial cues to improve speech
      detection in noise.

PMID- 21725260
TI  - Contemporary angiographic assessment and clinical implications of the vein of
      labbe in neurotologic surgery.
AB  - BACKGROUND: To better understand the drainage patterns of the 3 largest
      superficial anastomotic veins (SAVs), namely, vein of Labbe (VL), the vein of
      Trolard (VT), and the superficial sylvian vein (SSV). To assess the dominance of
      the VL in the superficial cortical venous system, because this vein may be
      encountered in neurotologic surgery and its interruption may result in a venous
      infarct of the temporal lobe. METHODS: The database of the radiology department
      at the University of Cincinnati was used to identify all patients who underwent a
      diagnostic angiographic study between September 1, 2009, and January 1, 2010.
      Studies were excluded if there were intracranial masses or vascular lesions.
      Angiograms were assessed for the presence of the VL, VT, and SSV, as well as
      vessel dominance, determined by their relative calibers. RESULTS: A total of 101
      patients (81%) underwent bilateral and 48 unilateral angiography, for a total of
      250 studies. Mean age was 55 years (range, 16-83 yr). Seventy-seven patients
      (53%) were females. The most common pattern observed was the presence of all 3
      SAVs (78%). The VL was absent or poorly developed in 34 studies (14%) and was the
      dominant superficial vein in 51 (20%), of which 28 (55%) occurred on the right.
      CONCLUSION: Considerable variability is demonstrated in the drainage patterns of
      the SAVs. Care should be taken in neurotologic surgery to avoid injuring the VL
      because this may represent the single dominant drainage pathway of the lateral
      surface of the temporal lobe in a large number of patients.

PMID- 21725261
TI  - Erosion of the long process of the incus in revision stapes surgery:
      malleovestibular prosthesis or incus reconstruction with hydroxyapatite bone
      cement?
AB  - OBJECTIVE: To study hearing outcome in revision stapedotomy cases where extensive
      erosion of the long process of the incus was observed in a consecutive series
      where a malleovestibular prosthesis was used versus a consecutive series where
      hydroxyapatite (HA) bone cement was used to rebuild the eroded long process of
      the incus and integrate the prosthesis. PATIENTS: Twenty revision cases of
      surgically treated otosclerosis where extensive incus erosion was observed during
      revision surgery. INTERVENTION: In the earlier consecutive series, 10 cases were
      treated with malleovestibular prostheses. In the later consecutive series, 10
      cases were treated with HA bone cement to rebuild the incus-prosthesis interface.
      MAIN OUTCOME MEASURES: Air-bone gap, bone-conduction thresholds, and air
      conduction thresholds were evaluated preoperatively and at 1 to 3 months. Last
      audiometry available also was reported (median, 12 mo). Pure-tone averages were
      calculated according to the guidelines of the Committee on Hearing and
      Equilibrium for the evaluation of conductive hearing loss. Raw data were
      displayed in an Amsterdam Hearing Evaluation Plot. RESULTS: Six male patients and
      14 female patients were included. Age varied from 34 to 75 years (median, 53 yr).
      The median postoperative air-bone gap at last follow-up audiometry was 15.6 in
      the malleovestibular prosthesis group and 13.1 dB in the HA bone cement group. No
      short-term or intermediate-term adverse reactions or unsuspected bone conduction
      deteriorations were seen. CONCLUSION: HA bone cement can be successfully used to
      reconstruct the long process of the incus in case of extensive erosion of the
      long process. Intermediate-term hearing outcome is comparable to the outcome of a
      series of similar cases treated with malleovestibular prostheses. Because the
      placement of a malleovestibular prosthesis is technically more difficult and
      presents a high risk to the inner ear, we think HA bone cement can be a useful
      alternative in these difficult cases.

PMID- 21725262
TI  - Subperiosteal temporal pocket versus standard technique in cochlear implantation:
      a comparative clinical study.
AB  - OBJECTIVE: In the standard technique of cochlear implantation, the internal
      receiver-stimulator (IRS) is fixed into a socket drilled on the calvarial bone.
      In the subperiosteal technique, the IRS is fixed under the subperiosteal plane,
      and drilling is not necessary. The purpose of this study was to compare the
      subperiosteal and the standard techniques. STUDY DESIGN: Retrospective clinical
      study. SETTING: Tertiary referral center; cochlear implant program. PATIENTS: One
      hundred forty-eight patients who underwent cochlear implantation. INTERVENTION:
      The researcher who evaluated the patients was not informed which of the 2
      techniques was used on the patients and administered a visual analog scale (VAS)
      analysis. The duration of the operation, intraoperative and postoperative
      complications, and migration of the IRS were assessed. MAIN OUTCOME MEASURES: A
      VAS survey was administered to the patients or to their parents to evaluate the
      practicability of the implant. RESULTS: The duration of the operation was 73.4 +/
      17.8 minutes in the subperiosteal group and 105.5 +/- 17.8 minutes in the
      standard technique group. The difference was statistically significant.
      Intracranial complications or migration of the IRS was also not observed in any
      patient. The VAS score was 4.2 +/- 2.1 in the standard group and 4.3 +/- 1.9 in
      the subperiosteal group. The difference was not statistically significant.
      CONCLUSION: The subperiosteal technique can be safely and effectively used in
      cochlear implantation. Not only are there no intracranial complications and no
      migration of IRS was observed but also the mean operation time is reduced up to
      30% and none of the patients have reported difficulty with fixing of the external
      device.

PMID- 21725263
TI  - Intratympanic versus intravenous delivery of dexamethasone and dexamethasone
      sodium phosphate to cochlear perilymph.
AB  - OBJECTIVE: To measure dexamethasone concentrations in the plasma and perilymph of
      the human ear after intravenous (IV) and intratympanic (IT) administration and to
      compare these with previous studies with methylprednisolone. METHODS: Patients
      were administered dexamethasone by the IT or IV routes approximately 0.5 to 2
      hours before cochlear implantation. The IT dose of 1.6 to 7.2 mg (0.4-1.8 ml of a
      4 mg/ml solution) of dexamethasone sodium phosphate was administered by injection
      into the middle ear cavity through the external auditory canal via a 27-gauge
      needle passed through a small anterosuperior myringotomy. The IV dose of
      dexamethasone sodium phosphate was 0.17 mg/kg given as a single injection for 30
      seconds. A sample of perilymph (approximately 20 MUl) was collected using a
      needle passed through the round window, and blood was sampled simultaneously.
      Concentrations of free dexamethasone and dexamethasone sodium phosphate were
      measured using a validated liquid chromatography-tandem mass spectrometry method.
      RESULTS: In the 22 patients studied, 22 perilymph samples and 19 plasma samples
      were available and suitable for measurement. The median perilymph concentration
      of dexamethasone after IV injection of 0.17 mg/kg was 0.016 mg/L (n = 9; range,
      0.008-0.17), and 1.4 mg/L (n = 13; range, 0.1-16.3) after IT administration of
      approximately 4 mg. Perilymph concentrations were approximately 88-fold higher
      after IT compared with IV administration (p = 0.0004) or approximately 260 fold
      after correction for dosage. The median plasma concentration of dexamethasone
      after IV injection was 0.12 mg/L (n = 7; range, 0.07-0.14) and 0.003 mg/L (n =
      12; range, <0.0005-0.005) after IT injection. Plasma concentrations were
      approximately 40-fold lower (p = 0.0005) or approximately 13-fold lower after
      dose correction. Concentrations of dexamethasone sodium phosphate were more
      variable and were even higher in perilymph and lower in plasma. CONCLUSION:
      Administration of dexamethasone IT results in much higher perilymph
      concentrations and much lower plasma concentrations compared with IV
      administration.

PMID- 21725264
TI  - Verification of computed tomographic estimates of cochlear implant array
      position: a micro-CT and histologic analysis.
AB  - OBJECTIVE: To determine the efficacy of clinical computed tomographic (CT)
      imaging to verify postoperative electrode array placement in cochlear implant
      (CI) patients. STUDY DESIGN: Nine fresh cadaver heads underwent clinical CT
      scanning, followed by bilateral CI insertion and postoperative clinical CT
      scanning. Temporal bones were removed, trimmed, and scanned using micro-CT.
      Specimens were then dehydrated, embedded in either methyl methacrylate or LR
      White resin, and sectioned with a diamond wafering saw. Histology sections were
      examined by 3 blinded observers to determine the position of individual
      electrodes relative to soft tissue structures within the cochlea. Electrodes were
      judged to be within the scala tympani, scala vestibuli, or in an intermediate
      position between scalae. RESULTS: The position of the array could be estimated
      accurately from clinical CT scans in all specimens using micro-CT and histology
      as a criterion standard. Verification using micro-CT yielded 97% agreement, and
      histologic analysis revealed 95% agreement with clinical CT results. CONCLUSION:
      A composite, 3-dimensional image derived from a patient's preoperative and
      postoperative CT images using a clinical scanner accurately estimates the
      position of the electrode array as determined by micro-CT imaging and histologic
      analyses. Information obtained using the CT method provides valuable insight into
      numerous variables of interest to patient performance such as surgical technique,
      array design, and processor programming and troubleshooting.

PMID- 21725265
TI  - Otologic symptoms as initial manifestation of wegener granulomatosis: diagnostic
      dilemma.
AB  - OBJECTIVE: To show 7 cases of Wegener granulomatosis (WG) with early aural
      symptoms and to discuss the problems of otologic manifestation in WG. STUDY
      DESIGN: Retrospective case review. SETTING: : Tertiary care university hospital.
      PATIENTS: All patients were administered to the ENT University Department in
      Poznan in years 2002-2008 because of otitis media with effusion, facial palsy,
      sensorineural profound hypoacusis, hypoacusis combined with purulent discharge,
      and facial nerve palsy or progression of mixed type hypoacusis. INTERVENTIONS:
      Diagnostics and treatment. MAIN OUTCOME MEASURESL: Otologic symptoms as initial
      manifestation of WG diagnostic dilemma. RESULTS: The authors want to underline
      the young age of the patients, ranging from 32 to 46 years. The outcome of
      initially otologic cases, which developed generalized form of WG, was poor (the
      first patient died after 2 months, the second patient died after 7 days, the
      third had the pulmonary insufficiency in 2 months of observation, and the fourth
      had severe renal failure in 1 month), whereas the patients with localized disease
      have been successfully under control for 1 to 5 years. CONCLUSION: As WG often
      presents otologic symptoms, as an initial sign in some cases, it is important to
      take WG into consideration in atypical inflammatory states of the ear. The
      otologic onset of WG is very insidious, and prompt diagnosis in early stage of
      disease is a challenge. Focal and localized disease in the aural region might
      possibly require less aggressive therapy than acute-onset multi-organ disease and
      is connected with better prognosis.

PMID- 21725266
TI  - Prognostic factors of peripheral facial palsy: multivariate analysis followed by
      receiver operating characteristic and Kaplan-Meier analyses.
AB  - OBJECTIVE: To search for prognostic predictors and reexamine the usefulness of
      electroneurography (ENoG) in predicting the prognosis of peripheral facial palsy
      using statistical methods. STUDY DESIGN: Prospective study. SETTING: Tertiary
      referral center. PATIENTS: Consecutive 142 patients with Bell's palsy and 26 with
      Ramsay Hunt syndrome treated with steroid plus antiviral agents. INTERVENTIONS:
      Multivariate analysis was used to identify which factors, including Yanagihara
      grading score and ENoG, predict better recovery. Receiver operating
      characteristic (ROC) curves were constructed for ENoG and grading score. The
      cumulative recovery rate by ENoG was calculated using Kaplan-Meier analysis.
      Recovery was defined as the improvement of grading score to 36 points or more
      (full score, 40) without synkinesis. RESULTS: Multivariate analysis revealed that
      Ramsay Hunt syndrome, the worst grading score and ENoG were the significant
      prognostic predictors. The area under the ROC curve for ENoG was broader than
      those for grading score, indicating that ENoG was superior to grading score in
      terms of accuracy for prognosis prediction. The ROC curve revealed that more than
      85% degeneration on ENoG had the best specificity (77.8%) and sensitivity (71.4%)
      to predict nonrecovery. When ENoG was subjected to the analysis of cumulative
      recovery rate using Kaplan-Meier plots, patients with more than 85% degeneration
      on ENoG had significantly poorer prognosis. CONCLUSION: ENoG was the most
      effective factor for prediction of the prognosis of peripheral facial palsy, and
      more than 85% degeneration had the best specificity and sensitivity to predict
      nonrecovery.

PMID- 21725267
TI  - Acquired cholesteatoma: classification and outcomes.
AB  - OBJECTIVE: Reclassification of acquired cholesteatoma into the commonly observed
      presentations of this condition to provide a simple and clear grouping that
      indicates the pathology, management, and outcomes of the group cases. PATIENTS:
      Virgin acquired cholesteatoma cases from a single center managed from 1986 to
      2008 (515 cases). INTERVENTIONS: Cases were managed by transcanal (20%) or intact
      canal wall techniques. Wall repairs successively used autograft cartilage
      (transcanal and early intact canal wall mastoidectomy cases), hydroxylapatite
      plates (1989-2007), or titanium sheeting (2007). Drum repairs used cartilage
      perichondrial composite grafts. Assembly techniques were the preferred
      ossiculoplasty method. RESULTS: Distribution: attic, 41%; pars tensa, 45%; and
      combined attic-pars tensa, 14%. Unclassifiable cases (n = 14) were excluded.
      Contralateral disease was present in 15% and effusions in 34% during or after
      surgery. Cell formation was most extensive in attic disease, least in combined
      patterns. Ossicular pathology was worse in the collapsed drum cases. Attic cases
      had the best hearing outcomes but risked recurrent disease, which required
      precise countermeasures. Overall, the combined pattern group carried the worst
      prognosis. CONCLUSION: Compared with previous methods, the clinical
      classification proved simple, descriptive, and comprehensive. It provides a
      readily discerned practical basis for clinical management and research purposes.

PMID- 21725268
TI  - Effects of cigarette smoking on hearing recovery from noise-induced temporary
      hearing threshold shifts in mice.
AB  - HYPOTHESIS: Cigarette smoking may potentiate noise-induced hearing loss.
      BACKGROUND: Many epidemiological studies have shown that cigarette smoking is a
      major risk factor for noise-induced hearing loss. METHODS: BALB/c mice were
      exposed to passive smoking for 2 h/d for 2 weeks before exposure to 110-dB sound
      pressure level white noise for 3 hours once. Hearing was assessed via the
      auditory brainstem response with tone-burst stimulation and distortion product
      otoacoustic emissions before and at 1, 3, 5, 7, 14, 21, and 28 days after noise
      exposure. Oxidative stress and hypoxia were assessed by immunostaining with 8
      oxoG and hypoxia-inducible factor 1alpha, respectively. RESULTS: Control mice
      unexposed to both smoking and noise and mice exposed to smoking only showed no
      shift in hearing threshold. In contrast, mice exposed to noise only or smoking
      plus noise showed abrupt increases in hearing threshold. In mice exposed to noise
      only, hearing threshold returned to prenoise levels after 2 weeks. However, in
      mice exposed to smoking plus noise, the loss of hearing was significantly higher,
      and hearing threshold did not return to the pre-exposure levels until 4 weeks
      later. Positive staining with 8-oxoG and hypoxia-inducible factor 1alpha were
      observed in the inner ear of the smoking-only and smoking-plus-noise group
      similar to noise-only mice, whereas no positive staining was observed in control
      group. CONCLUSION: These results indicate that cigarette smoking may potentiate
      the harmful effects of noise on hearing and disturb the recovery mechanism in the
      cochlea.

PMID- 21725269
TI  - Simultaneous true stapes fixation and bilateral bony dehiscence between the
      internal carotid artery and the apex of the cochlea: the ultimate pitfall.
AB  - BACKGROUND: A dehiscence of a semicircular canal can mimic the audiologic
      characteristics of otosclerosis. OBJECTIVE: To present a unique case report of a
      patient presenting with stapes fixation due to otosclerosis but persisting
      conductive hearing loss after uneventful laser-assisted stapedotomy with
      interposition of an aWengen titanium clip stapes prosthesis. Eventually, a
      bilateral bony dehiscence between the apical turn of the cochlea and the internal
      carotid artery was eventually identified, which explained the persisting
      postoperative conductive hearing loss. A dehiscence of the semicircular canals
      was duly ruled out preoperatively. PATIENT: : Caucasian man aged 63 years.
      INTERVENTION: Laser-assisted stapedotomy with interposition of an aWengen
      titanium clip stapes prosthesis. Later on, the patient received a Bone-Anchored
      Hearing Aid. RESULTS: A 63-year-old man presented with a clinical and audiologic
      bilateral stapes fixation due to otosclerosis. A possible dehiscence of a
      semicircular canal was duly ruled out preoperatively by high-resolution computed
      tomographic scanning. The stapes fixation was treated lege artis by laser
      assisted stapedotomy and subsequent interposition of an aWengen titanium clip
      stapes prosthesis, but the mixed hearing loss persisted. Eventually, a dehiscence
      between the apical turn of the cochlea and the internal carotid artery was
      identified. Thereafter, the patient was adequately helped with a Bone-Anchored
      Hearing Aid. CONCLUSION: We think that this is the first published case of
      simultaneous occurrence of radiologically and preoperatively confirmed stapes
      fixation and bilateral bony dehiscence between the apex of the cochlea and the
      internal carotid artery. Preoperative imaging studies therefore should look not
      only for a possible dehiscence of a semicircular canal, mimicking otosclerosis,
      but also for a dehiscence between the cochlea and the internal carotid artery.

PMID- 21725270
TI  - Prognostic factors in herpes zoster oticus (ramsay hunt syndrome).
AB  - OBJECTIVES: To determine if an accurate prognosis can be made in patients with
      Herpes zoster oticus (HZO), facial nerve outcomes were assessed at 1-year after
      onset and compared with symptoms and signs at presentation. STUDY DESIGN:
      Individual retrospective cohort study of 101 records in a case series (level of
      evidence: Level 2b). METHODS: Symptoms, signs, audiology, and treatment records
      were analyzed to determine their association with facial nerve outcome at 1 year.
      RESULTS: Mean improvement at 1 year for the 101 patients was 3 House-Brackmann
      (HB) grade units. Initially, severity ranged from HB III to HB VI. Mean recovery
      was significantly greater for those patients who were initially more affected,
      although at 1 year, they had still not recovered to the same grade as those
      initially less affected. Having both incomplete eye closure and a dry eye was
      associated with less recovery at 1 year. The use of prednisone combined with an
      antiviral agent, and begun at or after Day 5 of the illness, was related to a
      better facial nerve outcome. No other symptom, sign, or audiologic feature was of
      prognostic value. CONCLUSION: All patients with HZO improved facial function to
      some degree, with the mean gain at 1 year after onset being 3 HB grade units.
      Improvement was less for patients who initially had both incomplete eye closure
      and dry eye. The group who received a combination of an antiviral medication with
      steroids given after 5 days had the best facial nerve outcome.

PMID- 21725271
TI  - Primary non-Hodgkin lymphoma of the petrous temporal bone.

PMID- 21725272
TI  - Langerhans' cell histiocytosis of the temporal bone.

PMID- 21725273
TI  - Inflammatory myofibroblastic tumor of the temporal bone.

PMID- 21725274
TI  - National survey of bedside ultrasound use in pediatric critical care.
AB  - OBJECTIVES: The use of bedside ultrasound in critically ill adults has become
      standard practice. The current state of bedside ultrasound use in pediatric
      critical illness is unknown. The purpose of this study was to describe the use of
      bedside ultrasound in critically ill children with an emphasis on its use for
      establishing central vascular access. We also sought to describe current methods
      of training for bedside ultrasound use in pediatric critical care. DESIGN: We
      conducted a cross-sectional survey on the use of bedside ultrasound in pediatric
      intensive care units in the United States. MEASUREMENTS AND MAIN RESULTS:
      Pediatric critical care medical directors or their representatives from 128 of
      230 eligible hospitals responded (56% response rate). The use of bedside
      ultrasound for vascular access was statistically more likely in units with >12
      beds, >1,000 yearly admissions, and those with an active fellowship or pediatric
      cardiothoracic surgery program. Ultrasound was used at least once for vascular
      access in 82% (105 of 128) of responders, with 86% (90 of 105) using it on a
      regular basis. When using bedside ultrasound for vascular access, the preferred
      site is the internal jugular vein. A significant portion of responders use
      bedside ultrasound for nonvascular procedures such as assessing pleural or
      pericardial effusions. Despite the widespread use of bedside ultrasound, formal
      training is rare, occurring in only 20% (18 of 90) of current institutions that
      utilize bedside ultrasound. CONCLUSIONS: This national survey of the use of
      bedside ultrasound in pediatric critical care reveals widespread use of the
      technology. When using bedside ultrasound for vascular access, the preferred site
      is the internal jugular vein. Despite widespread use of bedside ultrasound,
      formal training that occurs routinely in other subspecialties is lacking. This
      survey provides meaningful demographic data that can be useful in planning future
      prospective studies and implementing formal training in bedside ultrasound for
      pediatric critical care fellows.

PMID- 21725275
TI  - Mechanical ventilation in pediatric intensive care units during the season for
      acute lower respiratory infection: a multicenter study.
AB  - OBJECTIVE: To describe the characteristics and outcomes of mechanical ventilation
      in pediatric intensive care units during the season of acute lower respiratory
      infections. DESIGN: Prospective cohort of infants and children receiving
      mechanical ventilation for at least 12 hrs. SETTING: Sixty medical-surgical
      pediatric intensive care units. PATIENTS: All consecutive patients admitted to
      participating pediatric intensive care units during a 28-day period. MEASUREMENTS
      AND MAIN RESULTS: Of 2,156 patients admitted to pediatric intensive care units,
      1185 (55%) received mechanical ventilation for a median of 5 days (interquartile
      range 2-8). Median age was 7 months (interquartile range 2-25). Main indications
      for mechanical ventilation were acute respiratory failure in 78% of the patients,
      altered mental status in 15%, and acute on chronic pulmonary disease in 6%.
      Median length of stay in the pediatric intensive care units was 10 days
      (interquartile range 6-18). Overall mortality rate in pediatric intensive care
      units was 13% (95% confidence interval: 11-15) for the entire population, and 39%
      (95% confidence interval: 23 - 58) in patients with acute respiratory distress
      syndrome. Of 1150 attempts at liberation from mechanical ventilation, 62% (95%
      confidence interval: 60-65) used the spontaneous breathing trial, and 37% (95%
      confidence interval: 35-40) used gradual reduction of ventilatory support.
      Noninvasive mechanical ventilation was used initially in 173 patients (15%, 95%
      confidence interval: 13-17). CONCLUSION: In the season of acute lower respiratory
      infections, one of every two children admitted to pediatric intensive care units
      requires mechanical ventilation. Acute respiratory failure was the most common
      reason for mechanical ventilation. The spontaneous breathing trial was the most
      commonly used method for liberation from mechanical ventilation.

PMID- 21725276
TI  - Bias flow does not affect ventilation during high-frequency oscillatory
      ventilation in a pediatric animal model of acute lung injury.
AB  - OBJECTIVE: During high-frequency oscillatory ventilation, bias flow is the
      continuous flow of gas responsible for replenishing oxygen and removing CO(2)
      from the patient circuit. Bias flow is usually set at 20 L/min, but many patients
      require neuromuscular blockade at this flow rate. The need for neuromuscular
      blockade may be eliminated by increasing the bias flow rate, but CO(2) retention
      is a potential concern. We hypothesize that in a swine model of acute lung
      injury, increased bias flow rates will not affect CO(2) elimination. DESIGN:
      Prospective, randomized, experimental study. SETTING: Research laboratory at a
      university medical center. SUBJECTS: Sixteen juvenile swine. INTERVENTIONS:
      Sixteen juvenile swine (12-16.5 kg) were studied using a saline lavage model of
      acute lung injury. During high-frequency oscillatory ventilation, each animal was
      ventilated with bias flows of 10, 20, 30, and 40 L/min in random sequence. For
      ten animals, power was set at a constant level to maintain PaCO(2) 50-60 mm Hg,
      and amplitude was allowed to vary. For the remaining six animals, amplitude was
      kept constant to maintain PaCO(2) within the same range, while power was adjusted
      as needed with changes in bias flow. Linear regression was used for data
      analysis. MEASUREMENTS AND MAIN RESULTS: Median overall PaCO(2) was 53 mm Hg
      (range: 31-81 mm Hg). Controlling for both power and amplitude, there was no
      statistically significant change in PaCO(2) as bias flow varied from 10 to 40
      L/min. CONCLUSIONS: Changes in bias flow during high-frequency oscillatory
      ventilation did not affect ventilation. Further clinical investigation is ongoing
      in infants and children with acute lung injury being managed with high-frequency
      oscillatory ventilation to assess the impact of alterations of bias flow on gas
      exchange, cardiopulmonary parameters, sedation requirements, and other clinical
      outcomes.

PMID- 21725277
TI  - Myocardial dysfunction in neonatal sepsis: a tissue Doppler imaging study.
AB  - OBJECTIVES: To assess myocardial performance in septic full-term infants and to
      correlate it with serum cardiac troponin T concentrations. DESIGN: Prospective,
      case-control, clinical study. SETTING: Neonatal intensive care unit in a
      university hospital. PATIENTS: Twenty septic and 20 nonseptic full-term neonates.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Conventional
      echocardiography, tissue Doppler imaging, and serum cardiac troponin T
      concentration tests were performed as soon as diagnosis was made. On tissue
      Doppler imaging measurements, right ventricular and left ventricular Tei indexes
      were significantly higher in septic neonates compared to nonseptic neonates (mean
      +/- SD: 0.51 +/- 0.09 vs. 0.28 +/- 0.05, p < .001, and 0.56 +/- 0.07 vs. 0.39 +/-
      0.04, p < .001, respectively). Mitral and tricuspid peak annular systolic
      velocities were significantly lower in septic neonates (mean +/- SD: 4.35 +/-
      0.68 vs. 6.89 +/- 0.94 cm/sec, p < .0001, and 5.55 +/- 0.66 vs. 6.69 +/- 0.87
      cm/second, p < .0001, respectively). On conventional echocardiography
      measurements, left ventricular internal diameter at end-diastole was
      significantly higher in septic neonates (p = .04), whereas cardiac index and left
      ventricular and right ventricular diastolic functions were not significantly
      different between septic and nonseptic neonates. Cardiac troponin T
      concentrations were significantly higher in septic neonates (median [range], 0.19
      [0.12- 0.32] vs. 0.03 [0-0.07] mg/L, p < .0001), and they correlated positively
      with left ventricular Tei index (r = .80; p < .0001) and right ventricular Tei
      index (r = .73; p < .0001), and correlated negatively with mitral peak annular
      systolic velocity (r = -.70; p < .0001) and tricuspid peak annular systolic (r = 
      .39, p = .012). Nonsurvivors had significantly higher serum cardiac troponin T
      concentrations and left ventricular Tei index. CONCLUSIONS: Neonatal sepsis is
      associated with systolic and diastolic myocardial dysfunction. This study
      provides proof-of-concept data for the use of tissue Doppler imaging in
      assessment of myocardial dysfunction in septic neonates. Tissue Doppler imaging
      appears to be more sensitive than conventional echocardiography in the detection
      of this dysfunction. Serum cardiac troponin T and left ventricular Tei index may
      have prognostic value in these patients.

PMID- 21725278
TI  - NMR and UV studies of 4-thio-2'-deoxyuridine and its derivatives.
AB  - 5-Substituted-4-thio-2'-deoxyuridine nucleosides have been chemically synthesized
      and studied by NMR and UV spectroscopy. The results have been analyzed and
      discussed in connection with the previous data. The imino proton signal and the
      carbon signal of the thiocarbonyl group in the 5-substituted-4-thio-2'
      deoxyuridines were found to be at much lower field, offering a potential for
      monitoring these modified bases at the DNA level. All 4-thionucleosides have
      strong absorptions at around 340 nm and consequently would be useful as potential
      UVA-induced anticancer agents.

PMID- 21725279
TI  - Treatment of alcohols with tosyl chloride does not always lead to the formation
      of tosylates.
AB  - Treatment of substituted benzyl alcohols with tosyl chloride resulted in the
      formation of the corresponding chlorides, not the usual tosylates. A series of
      experiments demonstrated that it was possible to predict whether chlorination or
      tosylation would occur for substituted benzyl alcohols and pyridine methanols.
      Treatment of electron withdrawing group-substituted benzyl alcohols with tosyl
      chloride gave the corresponding chlorides in moderate yields under mild
      conditions, which provided a simple way to directly prepare chlorides from
      alcohols.

PMID- 21725280
TI  - The functions of the actin nucleator Cobl in cellular morphogenesis critically
      depend on syndapin I.
AB  - Spatial control of cortical actin nucleation is indispensable for proper
      establishment and plasticity of cell morphology. Cobl is a novel WH2 domain-based
      actin nucleator. The cellular coordination of Cobl's nucleation activity,
      however, has remained elusive. Here, we reveal that Cobl's cellular functions are
      dependent on syndapin. Cobl/syndapin complexes form in vivo, as demonstrated by
      colocalization, coimmunoprecipitation and subcellular recruitment studies. In
      vitro reconstitutions and subcellular fractionations demonstrate that, via its
      lipid-binding Fer/CIP4 Homology (FCH)-Bin/Amphiphysin/Rvs (F-BAR) domain,
      syndapin recruits Cobl to membranes. Consistently, syndapin I RNAi impairs
      cortical localization of Cobl. Further functional studies in neurons show that
      Cobl and syndapin I work together in dendritic arbor development. Importantly,
      both proteins are crucial for dendritogenesis. Cobl-mediated functions in
      neuromorphogenesis critically rely on syndapin I and interestingly also on Arp3.
      Endogenous Cobl, syndapin I and the Arp2/3 complex activator and syndapin-binding
      partner N-WASP were present in one complex, as demonstrated by
      coimmunoprecipitations. Together, these data provide detailed insights into the
      molecular basis for Cobl-mediated functions and reveal that different actin
      nucleators are functionally intertwined by syndapin I during neuromorphogenesis.

PMID- 21725281
TI  - Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation
      of T and mast cells.
AB  - Cooperatively assembled signalling complexes, nucleated by adaptor proteins,
      integrate information from surface receptors to determine cellular outcomes. In T
      and mast cells, antigen receptor signalling is nucleated by three adaptors: SLP
      76, Gads and LAT. Three well-characterized SLP-76 tyrosine phosphorylation sites
      recruit key components, including a Tec-family tyrosine kinase, Itk. We
      identified a fourth, evolutionarily conserved SLP-76 phosphorylation site, Y173,
      which was phosphorylated upon T-cell receptor stimulation in primary murine and
      Jurkat T cells. Y173 was required for antigen receptor-induced phosphorylation of
      phospholipase C-gamma1 (PLC-gamma1) in both T and mast cells, and for consequent
      downstream events, including activation of the IL-2 promoter in T cells, and
      degranulation and IL-6 production in mast cells. In intact cells, Y173
      phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of
      SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated
      Y173 in vitro. These data suggest a sequential mechanism whereby ZAP-70-dependent
      priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory
      interactions between Itk and SLP-76, which are ultimately required to couple
      active Itk to its substrate, PLC-gamma1.

PMID- 21725282
TI  - Activation of Src and transformation by an RPTPalpha splice mutant found in human
      tumours.
AB  - Receptor protein tyrosine phosphatase alpha (RPTPalpha)-mediated Src activation
      is required for survival of tested human colon and oestrogen receptor-negative
      breast cancer cell lines. To explore whether mutated RPTPalpha participates in
      human carcinogenesis, we sequenced RPTPalpha cDNAs from five types of human
      tumours and found splice mutants in ~30% of colon, breast, and liver tumours.
      RPTPalpha245, a mutant expressed in all three tumour types, was studied further.
      Although it lacks any catalytic domain, RPTPalpha245 expression in the tumours
      correlated with Src tyrosine dephosphorylation, and its expression in rodent
      fibroblasts activated Src by a novel mechanism. This involved RPTPalpha245
      binding to endogenous RPTPalpha (eRPTPalpha), which decreased eRPTPalpha-Grb2
      binding and increased eRPTPalpha dephosphorylation of Src without increasing non
      specific eRPTPalpha activity. RPTPalpha245-eRPTPalpha binding was blocked by
      Pro210 -> Leu/Pro211 -> Leu mutation, consistent with the involvement of the
      structural 'wedge' that contributes to eRPTPalpha homodimerization. RPTPalpha245
      induced fibroblast transformation was blocked by either Src or eRPTPalpha RNAi,
      indicating that this required the dephosphorylation of Src by eRPTPalpha. The
      transformed cells were tumourigenic in nude mice, suggesting that RPTPalpha245
      induced activation of Src in the human tumours may have contributed to
      carcinogenesis.

PMID- 21725283
TI  - Postdoctoral training: time for change.
AB  - The increasingly pressing problems facing postdoctoral fellows in recent years
      call for a re-evaluation of the position of postdocs in academia and
      collaboration of involved parties to bring about positive change.

PMID- 21725285
TI  - Might makes right: Using force to align the mitotic spindle.
AB  - Both symmetric and asymmetric divisions rely on alignment of the mitotic spindle
      with cues from the environment. A study now shows that mitotic spindles find
      their position by reading the map of forces that load-bearing retraction fibres
      exert on the cell body.

PMID- 21725286
TI  - Multi-talented MCAK: Microtubule depolymerizer with a strong grip.
AB  - Microtubule-depolymerizing motor proteins regulate microtubule dynamics during
      chromosome segregation, but whether they can independently grip the ends of
      shrinking kinetochore microtubules has remained unresolved. MCAK, a member of the
      kinesin-13 motor protein family, is now shown to grip microtubules on its own and
      harness the forces of microtubule disassembly.

PMID- 21725288
TI  - Chromosome 14q loss defines a molecular subtype of clear-cell renal cell
      carcinoma associated with poor prognosis.
AB  - Loss of chromosome 14 has been associated with poor outcomes in clear-cell renal
      cell carcinoma. Expression of HIFalpha isoforms has been linked to distinct
      molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that
      chromosome 14 loss could lead to a decrease in HIF1alpha levels, as its gene
      (HIF1A) resides in this chromosome. We analyzed 112 archival clear-cell renal
      cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated
      expression of HIFalpha isoforms by qPCR and immunohistochemistry in a subset of
      30 patients. Loss of chromosome 14q was associated with high stage (III-IV,
      P=0.001), high risk for recurrence (P=0.002, RR 2.78 (1.506-5.153)) and with
      decreased overall survival (P=0.030) in non-metastatic clear-cell renal cell
      carcinoma. HIF1alpha mRNA and protein expression was reduced in specimens with
      loss of 14q (P=0.014) whereas HIF2alpha was not. Gain of 8q was associated with
      decreased overall survival (P<0.0001). Our studies confirm an association between
      14q loss and clinical outcome in non-metastatic clear-cell renal cell carcinoma
      patients and that 8q gain is a candidate prognostic marker for decreased overall
      survival and appears to further decrease survival in patients with 14q loss. We
      have also identified that differential expression of HIF1alpha is associated with
      14q loss. Further exploration of 8q gain, 14q loss, MYC, HIF1A and EPAS1
      (HIF2alpha) as molecular markers of tumor behavior and prognosis could aid in
      personalizing medicine for patients with clear-cell renal cell carcinoma.

PMID- 21725289
TI  - FGFR2 alterations in endometrial carcinoma.
AB  - Fibroblast growth factor receptor 2 (FGFR2) is a tyrosine kinase receptor
      involved in many biological processes such as embryogenesis, adult tissue
      homeostasis and cell proliferation. Mutations in FGFR2 have been reported in up
      to 10-12% of endometrial carcinomas identical to those found in congenital
      craniofacial disorders. Inhibition of FGFR2 could be a new therapeutic target in
      endometrial carcinoma. FGFR2 immunostaining was assessed in three tissue
      microarrays: one constructed from paraffin-embedded blocks of 60 samples of
      normal endometrium in different phases of menstrual cycle, and two tissue
      microarrays containing endometrial carcinoma samples (95 and 62 cases). FGFR2
      expression was correlated with stage, histological type and grade as well as with
      immunostaining of PTEN, RASSF1A, estrogen and progesterone receptors, KI67,
      Cyclin D1, STAT-3 and SPRY2. FGFR2 mutations were assessed by PCR and direct
      sequencing, with DNA obtained from 31 paraffin-embedded endometrial carcinoma
      samples. In normal endometrium, FGFR2 expression was higher in the secretory than
      in the proliferative phase (P=0.001), with an inverse correlation with Ki67
      (P=0.00032), suggesting a tumor-suppressor role for FGFR2 in normal endometrium.
      Cytoplasmic expression of FGFR2 was higher in endometrial carcinoma when compared
      with the atrophic endometrium from the same patients (P=0.0283), but was lower in
      comparison with normal endometrium from women in the menstrual cycle.
      Interestingly, nuclear staining was observed in some cases, and it was less
      frequent in endometrial carcinoma when compared with the adjacent atrophic
      endometrium (P=0.0465). There were no statistical differences when comparing
      superficial and myoinvasive endometrial carcinoma samples. Endometrioid
      endometrial carcinomas showed higher expression of FGFR2 than nonendometrioid
      endometrial carcinomas (fold change 2.56; P=0.0015). Grade III endometrioid
      endometrial carcinomas showed decreased FGFR2 expression when compared with grade
      II endometrioid endometrial carcinomas (P=0.0055). No differences were found
      regarding pathological stage. Two missense mutations of FGFR2 gene were detected
      in exons 6 and 11 (S252W and N549K, respectively; 6.45%). Results support the
      hypothesis that FGFR2 has a dual role in the endometrium, by inhibiting cell
      proliferation in normal endometrium during the menstrual cycle, but acting as an
      oncogene in endometrial carcinoma.

PMID- 21725290
TI  - Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in
      bladder cancer subtypes and associated tumor neovasculature.
AB  - Folate hydrolase (prostate-specific antigen) 1 (FH(PSA)1), also known as prostate
      specific membrane antigen (PSMA), is a transmembrane receptor expressed on
      prostate cancer cells that correlates with a more aggressive phenotype. Recent
      studies have demonstrated FH(PSA)1 expression in numerous benign and malignant
      tissue types, as well as the malignant neovasculature. As FH(PSA)1 represents a
      diagnostic immunomarker for prostate cancer, we explored its expression pattern
      in various subtypes of bladder cancer. Immunohistochemical analysis (IHC) of
      FH(PSA)1 was performed using tissue microarrays constructed from 167 bladder
      cancers, including 96 urothelial carcinomas (UCCs), 37 squamous cell carcinomas,
      17 adenocarcinomas and 17 small cell carcinomas. We used a FH(PSA)1 monoclonal
      antibody obtained from Dako (clone 3E6, dilution 1:100), which recognizes the
      epitope present in the 57-134 amino acid region of the extracellular portion of
      the PSMA molecule. Intensity of IHC staining was scored as 0 (no expression) to
      3+ (strong expression), with 2-3+ IHC considered a positive result. FH(PSA)1
      demonstrated expression in a subset of bladder cancers and was most common in
      small cell carcinoma (3/17; 18%), with concurrent expression in non-small cell
      components in a subset of cases (2/6). FH(PSA)1 expression was less frequent in
      UCC (3/96; 3%) and adenocarcinoma (2/17; 12%). None of the squamous cell
      carcinomas demonstrated tumor cell expression of FH(PSA)1. However, all bladder
      cancers examined expressed FH(PSA)1 in the tumor vasculature, suggesting a
      potential role for this molecule in mediating new vessel ingrowth. FH(PSA)1 may
      occasionally be expressed in various subtypes of bladder cancer. These findings
      suggest cautious use of FH(PSA)1 as a diagnostic marker for prostatic tissue
      invading the bladder. The finding of FH(PSA)1 in the bladder cancer
      neovasculature suggests that this molecule may promote tumor growth and may
      represent a potential new vascular target in this disease.

PMID- 21725291
TI  - EWSR1 gene rearrangement occurs in a subset of cutaneous myoepithelial tumors: a
      study of 18 cases.
AB  - Cutaneous myoepithelial tumors form a clinicopathological spectrum ranging from
      mixed tumor to myoepithelioma and myoepithelial carcinoma. Recently, EWSR1
      rearrangement has been described in a subset of soft tissue myoepithelial tumors,
      whereas the cutaneous counterparts showed this aberration in a minority of cases.
      This raises the question whether cutaneous myoepithelial tumors have comparable
      genetic alterations. We examined 18 cases of cutaneous myoepithelial tumors
      arising in 7 female and 11 male patients (age range, 34-86 years; mean, 58
      years). Eight mixed tumors occurred at the head, and one at the scrotum. Six
      myoepitheliomas arose at the extremities, and one case each at the back and head.
      One myoepithelial carcinoma occurred at the cheek. The tumor size ranged from 0.3
      to 1.7 cm (mean, 1.0 cm). All mixed tumors and three myoepitheliomas were limited
      to the dermis. Four myoepitheliomas and the myoepithelial carcinoma involved the
      subcutis. Mixed tumors and myoepitheliomas were composed of myoepithelial cells
      with a variable cytomorphology, architecture and stromal background. Ductal
      structures were seen by definition in mixed tumors. The myoepithelial carcinoma
      represented an infiltrative dermal neoplasm consisting of atypical spindle cells.
      Immunohistochemically, all cases tested were positive for EMA and calponin,
      whereas S100, CK, ASMA and GFAP were expressed in 90%, 80%, 78% and 50% of the
      cases tested, respectively. By fluorescent in situ hybridization analysis, 7 out
      of 16 cases (44%) exhibited EWSR1 rearrangement. Four of them were mixed tumors,
      two were myoepitheliomas and one was a myoepithelial carcinoma, confirming that
      these lesions represent a spectrum of dermal myoepithelial tumors. Follow-up
      information, available for five patients (including the patient with a
      myoepithelial carcinoma), revealed no evidence of disease in all cases (range, 6
      72 months). Our study provides a genetic relationship of myoepithelial tumors of
      the skin with their counterparts in soft tissue, bone and visceral localization
      by sharing EWSR1 rearrangement.

PMID- 21725292
TI  - Crystal structure of gamma-tubulin complex protein GCP4 provides insight into
      microtubule nucleation.
AB  - Microtubule nucleation in all eukaryotes involves gamma-tubulin small complexes
      (gammaTuSCs) that comprise two molecules of gamma-tubulin bound to gamma-tubulin
      complex proteins (GCPs) GCP2 and GCP3. In many eukaryotes, multiple gammaTuSCs
      associate with GCP4, GCP5 and GCP6 into large gamma-tubulin ring complexes
      (gammaTuRCs). Recent cryo-EM studies indicate that a scaffold similar to
      gammaTuRCs is formed by lateral association of gammaTuSCs, with the C-terminal
      regions of GCP2 and GCP3 binding gamma-tubulin molecules. However, the exact role
      of GCPs in microtubule nucleation remains unknown. Here we report the crystal
      structure of human GCP4 and show that its C-terminal domain binds directly to
      gamma-tubulin. The human GCP4 structure is the prototype for all GCPs, as it can
      be precisely positioned within the gammaTuSC envelope, revealing the nature of
      protein-protein interactions and conformational changes regulating nucleation
      activity.

PMID- 21725293
TI  - Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal
      transition.
AB  - Epithelial-to-mesenchymal transition (EMT) is an extreme example of cell
      plasticity that is important for normal development, injury repair and malignant
      progression. Widespread epigenetic reprogramming occurs during stem cell
      differentiation and malignant transformation, but EMT-related epigenetic
      reprogramming is poorly understood. Here we investigated epigenetic modifications
      during EMT mediated by transforming growth factor beta. Although DNA methylation
      was unchanged during EMT, we found a global reduction in the heterochromatin mark
      H3 Lys9 dimethylation (H3K9Me2), an increase in the euchromatin mark H3 Lys4
      trimethylation (H3K4Me3) and an increase in the transcriptional mark H3 Lys36
      trimethylation (H3K36Me3). These changes depended largely on lysine-specific
      demethylase-1 (Lsd1), and loss of Lsd1 function had marked effects on EMT-driven
      cell migration and chemoresistance. Genome-scale mapping showed that chromatin
      changes were mainly specific to large organized heterochromatin K9 modifications
      (LOCKs), which suggests that EMT is characterized by reprogramming of specific
      chromatin domains across the genome.

PMID- 21725294
TI  - DNA secondary structures and epigenetic determinants of cancer genome evolution.
AB  - An unstable genome is a hallmark of many cancers. It is unclear, however, whether
      some mutagenic features driving somatic alterations in cancer are encoded in the
      genome sequence and whether they can operate in a tissue-specific manner. We
      performed a genome-wide analysis of 663,446 DNA breakpoints associated with
      somatic copy-number alterations (SCNAs) from 2,792 cancer samples classified into
      26 cancer types. Many SCNA breakpoints are spatially clustered in cancer genomes.
      We observed a significant enrichment for G-quadruplex sequences (G4s) in the
      vicinity of SCNA breakpoints and established that SCNAs show a strand bias
      consistent with G4-mediated structural alterations. Notably, abnormal
      hypomethylation near G4s-rich regions is a common signature for many SCNA
      breakpoint hotspots. We propose a mechanistic hypothesis that abnormal
      hypomethylation in genomic regions enriched for G4s acts as a mutagenic factor
      driving tissue-specific mutational landscapes in cancer.

PMID- 21725295
TI  - Selective removal of promoter nucleosomes by the RSC chromatin-remodeling
      complex.
AB  - Purified chromatin rings, excised from the PHO5 locus of Saccharomyces cerevisiae
      in transcriptionally repressed and activated states, were remodeled with RSC and
      ATP. Nucleosomes were translocated, and those originating on the promoter of
      repressed rings were removed, whereas those originating on the open reading frame
      (ORF) were retained. Treatment of the repressed rings with histone deacetylase
      diminished the removal of promoter nucleosomes. These findings point to a
      principle of promoter chromatin remodeling for transcription, namely that
      promoter specificity resides primarily in the nucleosomes rather than in the
      remodeling complex that acts upon them.

PMID- 21725296
TI  - Caspase 3-mediated stimulation of tumor cell repopulation during cancer
      radiotherapy.
AB  - In cancer treatment, apoptosis is a well-recognized cell death mechanism through
      which cytotoxic agents kill tumor cells. Here we report that dying tumor cells
      use the apoptotic process to generate potent growth-stimulating signals to
      stimulate the repopulation of tumors undergoing radiotherapy. Furthermore,
      activated caspase 3, a key executioner in apoptosis, is involved in the growth
      stimulation. One downstream effector that caspase 3 regulates is prostaglandin
      E(2) (PGE(2)), which can potently stimulate growth of surviving tumor cells.
      Deficiency of caspase 3 either in tumor cells or in tumor stroma caused
      substantial tumor sensitivity to radiotherapy in xenograft or mouse tumors. In
      human subjects with cancer, higher amounts of activated caspase 3 in tumor
      tissues are correlated with markedly increased rate of recurrence and death. We
      propose the existence of a cell death-induced tumor repopulation pathway in which
      caspase 3 has a major role.

PMID- 21725297
TI  - Death receptor 6 negatively regulates oligodendrocyte survival, maturation and
      myelination.
AB  - Survival and differentiation of oligodendrocytes are important for the
      myelination of central nervous system (CNS) axons during development and crucial
      for myelin repair in CNS demyelinating diseases such as multiple sclerosis. Here
      we show that death receptor 6 (DR6) is a negative regulator of oligodendrocyte
      maturation. DR6 is expressed strongly in immature oligodendrocytes and weakly in
      mature myelin basic protein (MBP)-positive oligodendrocytes. Overexpression of
      DR6 in oligodendrocytes leads to caspase 3 (casp3) activation and cell death.
      Attenuation of DR6 function leads to enhanced oligodendrocyte maturation,
      myelination and downregulation of casp3. Treatment with a DR6 antagonist antibody
      promotes remyelination in both lysolecithin-induced demyelination and
      experimental autoimmune encephalomyelitis (EAE) models. Consistent with the DR6
      antagoinst antibody studies, DR6-null mice show enhanced remyelination in both
      demyelination models. These studies reveal a pivotal role for DR6 signaling in
      immature oligodendrocyte maturation and myelination that may provide new
      therapeutic avenues for the treatment of demyelination disorders such as multiple
      sclerosis.

PMID- 21725298
TI  - A large-scale method to measure absolute protein phosphorylation stoichiometries.
AB  - The functional role of protein phosphorylation is impacted by its fractional
      stoichiometry. Thus, a comprehensive strategy to study phosphorylation dynamics
      should include an assessment of site stoichiometry. Here we report an integrated
      method that relies on phosphatase treatment and stable-isotope labeling to
      determine absolute stoichiometries of protein phosphorylation on a large scale.
      This approach requires the measurement of only a single ratio relating
      phosphatase-treated and mock-treated samples. Using this strategy we determined
      stoichiometries for 5,033 phosphorylation sites in triplicate analyses from
      Saccharomyces cerevisiae growing through mid-log phase. We validated
      stoichiometries at ten sites that represented the full range of values obtained
      using synthetic phosphopeptides and found excellent agreement. Using
      bioinformatics, we characterized the biological properties associated with
      phosphorylation sites with vastly differing absolute stoichiometries.

PMID- 21725299
TI  - Megapixel digital PCR.
AB  - We present a microfluidic 'megapixel' digital PCR device that uses surface
      tension-based sample partitioning and dehydration control to enable high-fidelity
      single DNA molecule amplification in 1,000,000 reactors of picoliter volume with
      densities up to 440,000 reactors cm(-2). This device achieves a dynamic range of
      10(7), single-nucleotide-variant detection below one copy per 100,000 wild-type
      sequences and the discrimination of a 1% difference in chromosome copy number.

PMID- 21725300
TI  - Functional ultrasound imaging of the brain.
AB  - We present functional ultrasound (fUS), a method for imaging transient changes in
      blood volume in the whole brain at better spatiotemporal resolution than with
      other functional brain imaging modalities. fUS uses plane-wave illumination at
      high frame rate and can measure blood volumes in smaller vessels than previous
      ultrasound methods. fUS identifies regions of brain activation and was used to
      image whisker-evoked cortical and thalamic responses and the propagation of
      epileptiform seizures in the rat brain.

PMID- 21725301
TI  - Two-photon polarization microscopy reveals protein structure and function.
AB  - Membrane proteins are a large, diverse group of proteins, serving a multitude of
      cellular functions. They are difficult to study because of their requirement of a
      lipid membrane for function. Here we show that two-photon polarization microscopy
      can take advantage of the cell membrane requirement to yield insights into
      membrane protein structure and function, in living cells and organisms. The
      technique allows sensitive imaging of G-protein activation, changes in
      intracellular calcium concentration and other processes, and is not limited to
      membrane proteins. Conveniently, many suitable probes for two-photon polarization
      microscopy already exist.

PMID- 21725302
TI  - Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion
      proteins.
AB  - The ability to regulate any protein of interest in living systems with small
      molecules remains a challenge. We hypothesized that appending a hydrophobic
      moiety to the surface of a protein would mimic the partially denatured state of
      the protein, thus engaging the cellular quality control machinery to induce its
      proteasomal degradation. We designed and synthesized bifunctional small molecules
      to bind a bacterial dehalogenase (the HaloTag protein) and present a hydrophobic
      group on its surface. Hydrophobic tagging of the HaloTag protein with an
      adamantyl moiety induced the degradation of cytosolic, isoprenylated and
      transmembrane HaloTag fusion proteins in cell culture. We demonstrated the in
      vivo utility of hydrophobic tagging by degrading proteins expressed in zebrafish
      embryos and by inhibiting Hras1(G12V)-driven tumor progression in mice.
      Therefore, hydrophobic tagging of HaloTag fusion proteins affords small-molecule
      control over any protein of interest, making it an ideal system for validating
      potential drug targets in disease models.

PMID- 21725303
TI  - Small-molecule displacement of a cryptic degron causes conditional protein
      degradation.
AB  - The ability to rapidly regulate the functions of specific proteins in living
      cells is a valuable tool for biological research. Here we describe a new
      technique by which the degradation of a specific protein is induced by a small
      molecule. A protein of interest is fused to a ligand-induced degradation (LID)
      domain, resulting in the expression of a stable and functional fusion protein.
      The LID domain is comprised of the FK506- and rapamycin-binding protein (FKBP)
      and a 19-amino-acid degron fused to the C terminus of FKBP. In the absence of the
      small molecule Shield-1, the degron is bound to the FKBP fusion protein and the
      protein is stable. When present, Shield-1 binds tightly to FKBP, displacing the
      degron and inducing rapid and processive degradation of the LID domain and any
      fused partner protein. Structure-function studies of the 19-residue peptide
      showed that a 4-amino-acid sequence within the peptide is responsible for
      degradation.

PMID- 21725304
TI  - Electrically pumped waveguide lasing from ZnO nanowires.
AB  - Ultraviolet semiconductor lasers are widely used for applications in photonics,
      information storage, biology and medical therapeutics. Although the performance
      of gallium nitride ultraviolet lasers has improved significantly over the past
      decade, demand for lower costs, higher powers and shorter wavelengths has
      motivated interest in zinc oxide (ZnO), which has a wide direct bandgap and a
      large exciton binding energy. ZnO-based random lasing has been demonstrated with
      both optical and electrical pumping, but random lasers suffer from reduced output
      powers, unstable emission spectra and beam divergence. Here, we demonstrate
      electrically pumped Fabry-Perot type waveguide lasing from laser diodes that
      consist of Sb-doped p-type ZnO nanowires and n-type ZnO thin films. The diodes
      exhibit highly stable lasing at room temperature, and can be modelled with finite
      difference time-domain methods.

PMID- 21725305
TI  - Interfacial phase-change memory.
AB  - Phase-change memory technology relies on the electrical and optical properties of
      certain materials changing substantially when the atomic structure of the
      material is altered by heating or some other excitation process. For example,
      switching the composite Ge(2)Sb(2)Te(5) (GST) alloy from its covalently bonded
      amorphous phase to its resonantly bonded metastable cubic crystalline phase
      decreases the resistivity by three orders of magnitude, and also increases
      reflectivity across the visible spectrum. Moreover, phase-change memory based on
      GST is scalable, and is therefore a candidate to replace Flash memory for non
      volatile data storage applications. The energy needed to switch between the two
      phases depends on the intrinsic properties of the phase-change material and the
      device architecture; this energy is usually supplied by laser or electrical
      pulses. The switching energy for GST can be reduced by limiting the movement of
      the atoms to a single dimension, thus substantially reducing the entropic losses
      associated with the phase-change process. In particular, aligning the c-axis of a
      hexagonal Sb(2)Te(3) layer and the <111> direction of a cubic GeTe layer in a
      superlattice structure creates a material in which Ge atoms can switch between
      octahedral sites and lower-coordination sites at the interface of the
      superlattice layers. Here we demonstrate GeTe/Sb(2)Te(3) interfacial phase-change
      memory (IPCM) data storage devices with reduced switching energies, improved
      write-erase cycle lifetimes and faster switching speeds.

PMID- 21725306
TI  - Thick lead-free ferroelectric films with high Curie temperatures through
      nanocomposite-induced strain.
AB  - Ferroelectric materials are used in applications ranging from energy harvesting
      to high-power electronic transducers. However, industry-standard ferroelectric
      materials contain lead, which is toxic and environmentally unfriendly. The
      preferred alternative, BaTiO(3), is non-toxic and has excellent ferroelectric
      properties, but its Curie temperature of ~130  degrees C is too low to be
      practical. Strain has been used to enhance the Curie temperature of BaTiO(3)
      (ref. 4) and SrTiO(3) (ref. 5) films, but only for thicknesses of tens of
      nanometres, which is not thick enough for many device applications. Here, we
      increase the Curie temperature of micrometre-thick films of BaTiO(3) to at least
      330  degrees C, and the tetragonal-to-cubic structural transition temperature to
      beyond 800  degrees C, by interspersing stiff, self-assembled vertical columns of
      Sm(2)O(3) throughout the film thickness. The columns, which are 10 nm in
      diameter, strain the BaTiO(3) matrix by 2.35%, forcing it to maintain its
      tetragonal structure and resulting in the highest BaTiO(3) transition
      temperatures so far.

PMID- 21725307
TI  - A transition zone complex regulates mammalian ciliogenesis and ciliary membrane
      composition.
AB  - Mutations affecting ciliary components cause ciliopathies. As described here, we
      investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and
      found that it is essential for ciliogenesis in some, but not all, tissues. Cell
      types that do not require Tctn1 for ciliogenesis require it to localize select
      membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and
      Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with
      Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1,
      Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone,
      a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2,
      Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary
      membrane composition. Consistent with a shared function for complex components,
      we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a
      transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary
      assembly and trafficking, suggesting that transition zone dysfunction is the
      cause of these ciliopathies.

PMID- 21725308
TI  - A genome-wide association study identifies two new lung cancer susceptibility
      loci at 13q12.12 and 22q12.2 in Han Chinese.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. To identify
      genetic factors that modify the risk of lung cancer in individuals of Chinese
      ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331
      individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage
      validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined
      analyses identified six well-replicated SNPs with independent effects and
      significant lung cancer associations (P < 5.0 * 10(-8)) located in TP63
      (rs4488809 at 3q28, P = 7.2 * 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at
      5p15.33, P = 1.2 * 10(-20) and P = 1.0 * 10(-27), respectively), MIPEP-TNFRSF19
      (rs753955 at 13q12.12, P = 1.5 * 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and
      rs36600 at 22q12.2, P = 1.1 * 10(-11) and P = 6.2 * 10(-13), respectively). Two
      of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese
      population. These results suggest that genetic variants in 3q28, 5p15.33,
      13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han
      Chinese.

PMID- 21725309
TI  - Variation in the DEPDC5 locus is associated with progression to hepatocellular
      carcinoma in chronic hepatitis C virus carriers.
AB  - Chronic viral hepatitis is the most important risk factor for progression to
      hepatocellular carcinoma (HCC). To identify genetic risk factors for progression
      to HCC in individuals with chronic hepatitis C virus (HCV), we analyzed 467,538
      SNPs in 212 Japanese individuals with chronic HCV with HCC and 765 individuals
      with chronic HCV without HCC. We identified one intronic SNP in the DEPDC5 locus
      on chromosome 22 associated with HCC risk and confirmed the association using an
      independent case-control population (710 cases and 1,625 controls). The
      association was highly significant when we analyzed the stages separately as well
      as together (rs1012068, P(combined) = 1.27 * 10(-13), odds ratio = 1.75). The
      significance level of the association further increased after adjustment for
      gender, age and platelet count (P = 1.35 * 10(-14), odds ratio = 1.96). Our
      findings suggest that common variants within the DEPDC5 locus affect
      susceptibility to HCC in Japanese individuals with chronic HCV infection.

PMID- 21725310
TI  - Extensive genomic and transcriptional diversity identified through massively
      parallel DNA and RNA sequencing of eighteen Korean individuals.
AB  - Massively parallel sequencing technologies have identified a broad spectrum of
      human genome diversity. Here we deep sequenced and correlated 18 genomes and 17
      transcriptomes of unrelated Korean individuals. This has allowed us to construct
      a genome-wide map of common and rare variants and also identify variants formed
      during DNA-RNA transcription. We identified 9.56 million genomic variants, 23.2%
      of which appear to be previously unidentified. From transcriptome sequencing, we
      discovered 4,414 transcripts not previously annotated. Finally, we revealed 1,809
      sites of transcriptional base modification, where the transcriptional landscape
      is different from the corresponding genomic sequences, and 580 sites of allele
      specific expression. Our findings suggest that a considerable number of
      unexplored genomic variants still remain to be identified in the human genome,
      and that the integrated analysis of genome and transcriptome sequencing is
      powerful for understanding the diversity and functional aspects of human genomic
      variants.

PMID- 21725311
TI  - Owl's behavior and neural representation predicted by Bayesian inference.
AB  - The owl captures prey using sound localization. In the classical model, the owl
      infers sound direction from the position of greatest activity in a brain map of
      auditory space. However, this model fails to describe the actual behavior.
      Although owls accurately localize sources near the center of gaze, they
      systematically underestimate peripheral source directions. We found that this
      behavior is predicted by statistical inference, formulated as a Bayesian model
      that emphasizes central directions. We propose that there is a bias in the neural
      coding of auditory space, which, at the expense of inducing errors in the
      periphery, achieves high behavioral accuracy at the ethologically relevant range.
      We found that the owl's map of auditory space decoded by a population vector is
      consistent with the behavioral model. Thus, a probabilistic model describes both
      how the map of auditory space supports behavior and why this representation is
      optimal.

PMID- 21725312
TI  - A CaMKIIbeta signaling pathway at the centrosome regulates dendrite patterning in
      the brain.
AB  - The protein kinase calcium/calmodulin-dependent kinase II (CaMKII) predominantly
      consists of the alpha and beta isoforms in the brain. Although CaMKIIalpha
      functions have been elucidated, the isoform-specific catalytic functions of
      CaMKIIbeta have remained unknown. Using knockdown analyses in primary rat neurons
      and in the rat cerebellar cortex in vivo, we report that CaMKIIbeta operates at
      the centrosome in a CaMKIIalpha-independent manner to drive dendrite retraction
      and pruning. We also find that the targeting protein PCM1 (pericentriolar
      material 1) localizes CaMKIIbeta to the centrosome. Finally, we uncover the E3
      ubiquitin ligase Cdc20-APC (cell division cycle 20-anaphase promoting complex) as
      a centrosomal substrate of CaMKIIbeta. CaMKIIbeta phosphorylates Cdc20 at Ser51,
      which induces Cdc20 dispersion from the centrosome, thereby inhibiting
      centrosomal Cdc20-APC activity and triggering the transition from growth to
      retraction of dendrites. Our findings define a new, isoform-specific function for
      CaMKIIbeta that regulates ubiquitin signaling at the centrosome and thereby
      orchestrates dendrite patterning, with important implications for neuronal
      connectivity in the brain.

PMID- 21725313
TI  - Potent amyloidogenicity and pathogenicity of Abeta43.
AB  - The amyloid-beta peptide Abeta42 is known to be a primary amyloidogenic and
      pathogenic agent in Alzheimer's disease. However, the role of Abeta43, which is
      found just as frequently in the brains of affected individuals, remains
      unresolved. We generated knock-in mice containing a pathogenic presenilin-1 R278I
      mutation that causes overproduction of Abeta43. Homozygosity was embryonic
      lethal, indicating that the mutation involves a loss of function. Crossing
      amyloid precursor protein transgenic mice with heterozygous mutant mice resulted
      in elevated Abeta43, impairment of short-term memory and acceleration of amyloid
      beta pathology, which accompanied pronounced accumulation of Abeta43 in plaque
      cores similar in biochemical composition to those observed in the brains of
      affected individuals. Consistently, Abeta43 showed a higher propensity to
      aggregate and was more neurotoxic than Abeta42. Other pathogenic presenilin
      mutations also caused overproduction of Abeta43 in a manner correlating with
      Abeta42 and with the age of disease onset. These findings indicate that Abeta43,
      an overlooked species, is potently amyloidogenic, neurotoxic and abundant in
      vivo.

PMID- 21725314
TI  - Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A
      subunit.
AB  - Zinc is abundant in the central nervous system and regulates pain, but the
      underlying mechanisms are unknown. In vitro studies have shown that extracellular
      zinc modulates a plethora of signaling membrane proteins, including NMDA
      receptors containing the NR2A subunit, which display exquisite zinc sensitivity.
      We created NR2A-H128S knock-in mice to investigate whether Zn2+-NR2A interaction
      influences pain control. In these mice, high-affinity (nanomolar) zinc inhibition
      of NMDA currents was lost in the hippocampus and spinal cord. Knock-in mice
      showed hypersensitivity to radiant heat and capsaicin, and developed enhanced
      allodynia in inflammatory and neuropathic pain models. Furthermore, zinc-induced
      analgesia was completely abolished under both acute and chronic pain conditions.
      Our data establish that zinc is an endogenous modulator of excitatory
      neurotransmission in vivo and identify a new mechanism in pain processing that
      relies on NR2A NMDA receptors. The study also potentially provides a molecular
      basis for the pain-relieving effects of dietary zinc supplementation.

PMID- 21725315
TI  - Laminin-332 coordinates mechanotransduction and growth cone bifurcation in
      sensory neurons.
AB  - Laminin-332 is a major component of the dermo-epidermal skin basement membrane
      and maintains skin integrity. The transduction of mechanical force into
      electrical signals by sensory endings in the skin requires mechanosensitive
      channels. We found that mouse epidermal keratinocytes produce a matrix that is
      inhibitory for sensory mechanotransduction and that the active molecular
      component is laminin-332. Substrate-bound laminin-332 specifically suppressed one
      type of mechanosensitive current (rapidly adapting) independently of integrin
      receptor activation. This mechanotransduction suppression could be exerted
      locally and was mediated by preventing the formation of protein tethers necessary
      for current activation. We also found that laminin-332 could locally control
      sensory axon branching behavior. Loss of laminin-332 in humans led to increased
      sensory terminal branching and may lead to a de-repression of mechanosensitive
      currents. These previously unknown functions for this matrix molecule may explain
      some of the extreme pain experienced by individuals with epidermolysis bullosa
      who are deficient in laminin-332.

PMID- 21725316
TI  - The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to
      control centrosome duplication.
AB  - Deregulated centrosome duplication can result in genetic instability and
      contribute to tumorigenesis. Here, we show that centrosome duplication is
      regulated by the activity of an E3-ubiquitin ligase that employs the F-box
      protein FBXW5 (ref. 3) as its targeting subunit. Depletion of endogenous FBXW5 or
      overexpression of an F-box-deleted mutant version results in centrosome
      overduplication and formation of multipolar spindles. We identify the centriolar
      protein HsSAS-6 (refs 4,5) as a critical substrate of the SCF-FBXW5 complex.
      FBXW5 binds HsSAS-6 and promotes its ubiquitylation in vivo. The activity of SCF
      FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which
      phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6.
      FBXW5 is a cell-cycle-regulated protein with expression levels peaking at the
      G1/S transition. We show that FBXW5 levels are controlled by the anaphase
      promoting (APC/C) complex, which targets FBXW5 for degradation during mitosis and
      G1, thereby helping to reset the centrosome duplication machinery. In summary, we
      show that a cell-cycle-regulated SCF complex is regulated by the kinase PLK4, and
      that this in turn restricts centrosome re-duplication through degradation of the
      centriolar protein HsSAS-6.

PMID- 21725317
TI  - COPI acts in both vesicular and tubular transport.
AB  - Intracellular transport occurs through two general types of carrier, either
      vesicles or tubules. Coat proteins act as the core machinery that initiates
      vesicle formation, but the counterpart that initiates tubule formation has been
      unclear. Here, we find that the coat protein I (COPI) complex initially drives
      the formation of Golgi buds. Subsequently, a set of opposing lipid enzymatic
      activities determines whether these buds become vesicles or tubules.
      Lysophosphatidic acid acyltransferase-gamma (LPAATgamma) promotes COPI vesicle
      fission for retrograde vesicular transport. In contrast, cytosolic phospholipase
      A2-alpha (cPLA2alpha) inhibits this fission event to induce COPI tubules, which
      act in anterograde intra-Golgi transport and Golgi ribbon formation. These
      findings not only advance a molecular understanding of how COPI vesicle fission
      is achieved, but also provide insight into how COPI acts in intra-Golgi transport
      and reveal an unexpected mechanistic relationship between vesicular and tubular
      transport.

PMID- 21725318
TI  - The SNXy flavours of endosomal sorting.
AB  - The retromer complex coordinates retrograde transport of cargo proteins between
      endosomes and the trans-Golgi network. The sorting nexin SNX3 is required for the
      retrograde trafficking of Wntless, but not of other retrograde cargo proteins,
      revealing that the cargo specificity of retromer is provided by the sorting
      nexins.

PMID- 21725319
TI  - A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt
      sorting receptor Wntless and is required for Wnt secretion.
AB  - Wnt proteins are lipid-modified glycoproteins that play a central role in
      development, adult tissue homeostasis and disease. Secretion of Wnt proteins is
      mediated by the Wnt-binding protein Wntless (Wls), which transports Wnt from the
      Golgi network to the cell surface for release. It has recently been shown that
      recycling of Wls through a retromer-dependent endosome-to-Golgi trafficking
      pathway is required for efficient Wnt secretion, but the mechanism of this
      retrograde transport pathway is poorly understood. Here, we report that Wls
      recycling is mediated through a retromer pathway that is independent of the
      retromer sorting nexins SNX1-SNX2 and SNX5-SNX6. We have found that the unrelated
      sorting nexin, SNX3, has an evolutionarily conserved function in Wls recycling
      and Wnt secretion and show that SNX3 interacts directly with the cargo-selective
      subcomplex of the retromer to sort Wls into a morphologically distinct retrieval
      pathway. These results demonstrate that SNX3 is part of an alternative retromer
      pathway that functionally separates the retrograde transport of Wls from other
      retromer cargo.

PMID- 21725320
TI  - The orphan nuclear receptor SHP acts as a negative regulator in inflammatory
      signaling triggered by Toll-like receptors.
AB  - The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional
      corepressor that regulates hepatic metabolic pathways. Here we identified a role
      for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered
      inflammatory responses. SHP-deficient mice were more susceptible to endotoxin
      induced sepsis. SHP had dual regulatory functions in a canonical transcription
      factor NF-kappaB signaling pathway, acting as both a repressor of transactivation
      of the NF-kappaB subunit p65 and an inhibitor of polyubiquitination of the
      adaptor TRAF6. SHP-mediated inhibition of signaling via the TLR was mimicked by
      macrophage-stimulating protein (MSP), a strong inducer of SHP expression, via an
      AMP-activated protein kinase-dependent signaling pathway. Our data identify a
      previously unrecognized role for SHP in the regulation of TLR signaling.

PMID- 21725321
TI  - The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and
      the survival of Ly6C- monocytes.
AB  - The transcription factors that regulate differentiation into the monocyte subset
      in bone marrow have not yet been identified. Here we found that the orphan
      nuclear receptor NR4A1 controlled the differentiation of Ly6C- monocytes. Ly6C-
      monocytes, which function in a surveillance role in circulation, were absent from
      Nr4a1-/- mice. Normal numbers of myeloid progenitor cells were present in Nr4a1-/
      mice, which indicated that the defect occurred during later stages of monocyte
      development. The defect was cell intrinsic, as wild-type mice that received bone
      marrow from Nr4a1-/- mice developed fewer patrolling monocytes than did
      recipients of wild-type bone marrow. The Ly6C- monocytes remaining in the bone
      marrow of Nr4a1-/- mice were arrested in S phase of the cell cycle and underwent
      apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and
      survival of 'patrolling' Ly6C- monocytes.

PMID- 21725322
TI  - Controlled enhancement of spin-current emission by three-magnon splitting.
AB  - Spin currents--the flow of angular momentum without the simultaneous transfer of
      electrical charge--play an enabling role in the field of spintronics. Unlike the
      charge current, the spin current is not a conservative quantity within the
      conduction carrier system. This is due to the presence of the spin-orbit
      interaction that couples the spin of the carriers to angular momentum in the
      lattice. This spin-lattice coupling acts also as the source of damping in
      magnetic materials, where the precessing magnetic moment experiences a torque
      towards its equilibrium orientation; the excess angular momentum in the magnetic
      subsystem flows into the lattice. Here we show that this flow can be reversed by
      the three-magnon splitting process and experimentally achieve the enhancement of
      the spin current emitted by the interacting spin waves. This mechanism triggers
      angular momentum transfer from the lattice to the magnetic subsystem and modifies
      the spin-current emission. The finding illustrates the importance of magnon
      magnon interactions for developing spin-current based electronics.

PMID- 21725323
TI  - Architecture of the Mediator head module.
AB  - Mediator is a key regulator of eukaryotic transcription, connecting activators
      and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II).
      In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a
      total mass of more than one megadalton (refs 5, 6) and is organized into three
      modules, called head, middle/arm and tail. Our understanding of Mediator assembly
      and its role in regulating transcription has been impeded so far by limited
      structural information. Here we report the crystal structure of the essential
      Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a
      resolution of 4.3 angstroms. Our structure reveals three distinct domains, with
      the integrity of the complex centred on a bundle of ten helices from five
      different head subunits. An intricate pattern of interactions within this helical
      bundle ensures the stable assembly of the head subunits and provides the binding
      sites for general transcription factors and Pol II. Our structural and functional
      data suggest that the head module juxtaposes transcription factor IIH and the
      carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating
      phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal
      architectural principles underlying the role of Mediator in the regulation of
      gene expression.

PMID- 21725324
TI  - Direct generation of functional dopaminergic neurons from mouse and human
      fibroblasts.
AB  - Transplantation of dopaminergic neurons can potentially improve the clinical
      outcome of Parkinson's disease, a neurological disorder resulting from
      degeneration of mesencephalic dopaminergic neurons. In particular,
      transplantation of embryonic-stem-cell-derived dopaminergic neurons has been
      shown to be efficient in restoring motor symptoms in conditions of dopamine
      deficiency. However, the use of pluripotent-derived cells might lead to the
      development of tumours if not properly controlled. Here we identified a minimal
      set of three transcription factors--Mash1 (also known as Ascl1), Nurr1 (also
      known as Nr4a2) and Lmx1a--that are able to generate directly functional
      dopaminergic neurons from mouse and human fibroblasts without reverting to a
      progenitor cell stage. Induced dopaminergic (iDA) cells release dopamine and show
      spontaneous electrical activity organized in regular spikes consistent with the
      pacemaker activity featured by brain dopaminergic neurons. The three factors were
      able to elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts
      from healthy donors and Parkinson's disease patients. Direct generation of iDA
      cells from somatic cells might have significant implications for understanding
      critical processes for neuronal development, in vitro disease modelling and cell
      replacement therapies.

PMID- 21725326
TI  - Foreword to Men's Health in Asia: special issue of Asian Journal of Andrology.

PMID- 21725325
TI  - Coordination of DNA replication and histone modification by the Rik1-Dos2
      complex.
AB  - Histone modification marks have an important role in many chromatin processes.
      During DNA replication, both heterochromatin and euchromatin are disrupted ahead
      of the replication fork and are then reassembled into their original epigenetic
      states behind the fork. How histone marks are accurately inherited from
      generation to generation is still poorly understood. In fission yeast
      (Schizosaccharomyces pombe), RNA interference (RNAi)-mediated histone methylation
      is cell cycle regulated. Centromeric repeats are transiently transcribed in the S
      phase of the cell cycle and are processed into short interfering RNAs (siRNAs) by
      the complexes RITS (RNA-induced initiation of transcriptional gene silencing) and
      RDRC (RNA-directed RNA polymerase complex). The small RNAs together with
      silencing factors-including Dos1 (also known as Clr8 and Raf1), Dos2 (also known
      as Clr7 and Raf2), Rik1 and Lid2-promote heterochromatic methylation of histone
      H3 at lysine 9 (H3K9) by a histone methyltransferase, Clr4 (refs 8-13). The
      methylation of H3K9 provides a binding site for Swi6, a structural and functional
      homologue of metazoan heterochromatin protein 1 (HP1). Here we characterize a
      silencing complex in fission yeast that contains Dos2, Rik1, Mms19 and Cdc20 (the
      catalytic subunit of DNA polymerase-epsilon). This complex regulates RNA
      polymerase II (RNA Pol II) activity in heterochromatin and is required for DNA
      replication and heterochromatin assembly. Our findings provide a molecular link
      between DNA replication and histone methylation, shedding light on how epigenetic
      marks are transmitted during each cell cycle.

PMID- 21725327
TI  - Afterword to men's health in Asia: special issue of Asian Journal of Andrology.

PMID- 21725329
TI  - The significance of testosterone for fair participation of the female sex in
      competitive sports.

PMID- 21725330
TI  - Second to fourth digit ratio: a predictor of adult penile length.
AB  - The second to fourth digit ratio (2D:4D) has been proposed as a putative
      biomarker for prenatal testosterone and covaries with the sensitivity of the
      androgen receptor (AR). Both prenatal testosterone and the AR play a central role
      in penile growth. In this study, we investigated the relationship between digit
      ratio and penile length. Korean men who were hospitalized for urological surgery
      at a single tertiary academic centre were examined in this study, and 144 men
      aged 20 years or older who gave informed consent were prospectively enrolled.
      Right-hand second- and fourth-digit lengths were measured by a single
      investigator prior to measurement of penile length. Under anaesthesia, flaccid
      and stretched penile lengths were measured by another investigator who did not
      measure nor have any the information regarding the digit lengths. Univariate and
      multivariate analysis using linear regression models showed that only height was
      a significant predictive factor for flaccid penile length (univariate analysis:
      r=0.185, P=0.026; multivariate analysis: r=0.172, P=0.038) and that only digit
      ratio was a significant predictive factor for stretched penile length (univariate
      analysis:r=-0.216, P=0.009; multivariate analysis: r=-0.201, P=0.024; stretched
      penile length=-9.201*digit ratio + 20.577). Based on this evidence, we suggest
      that the digit ratio can predict adult penile size and that the effects of
      prenatal testosterone may in part explain the differences in adult penile length.

PMID- 21725331
TI  - Does digit ratio (2D:4D) predict penile length?

PMID- 21725332
TI  - The ability of sperm selection techniques to remove single- or double-strand DNA
      damage.
AB  - A wide variety of techniques for the preparation of sperm are currently
      available, of which the most commonly employed are density-gradient
      centrifugation (DGC) and swim-up (SUP). To date, these methods appear to be
      effective in selecting functional sperm for assisted reproduction techniques
      (ART), but they may have negative effects on sperm DNA. In this study, the
      ability of these semen processing techniques to eliminate spermatozoa containing
      single- and double-strand DNA damage was assessed by the two-tailed comet assay
      and the sperm chromatin dispersion test in 157 semen samples from patients
      seeking assisted reproduction treatment. Our results indicated that SUP and DGC
      are equally efficient in eliminating spermatozoa containing double-strand DNA
      damage and sperm with highly damaged (degraded) DNA, as characterized by the
      presence of both single- and double-strand DNA breaks. However, DGC is more
      efficient than SUP in selecting spermatozoa that are free from single-strand DNA
      damage. Future studies should characterise the importance of the various types of
      DNA damage and examine the sperm processing protocols used in each laboratory to
      determine their ability to eliminate DNA damage and hence, prevent the potential
      transmission of genetic mutations via ART.

PMID- 21725333
TI  - DNA methylome and the complexity of discovering prostate cancer biomarkers.

PMID- 21725334
TI  - Where medicine meets the boundaries of manhood and womanhood.

PMID- 21725335
TI  - MicroRNA regulation of innate immune responses in epithelial cells.
AB  - Mucosal surface epithelial cells are equipped with several defense mechanisms
      that guard against pathogens. Recent studies indicate that microRNAs (miRNAs)
      mediate post-transcriptional gene suppression and may be a critical component of
      the complex regulatory networks in epithelial immune responses. Transcription of
      miRNA genes in epithelial cells can be elaborately controlled through pathogen
      recognition receptors, such as Toll-like receptors (TLRs), and associated nuclear
      factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways,
      and ultimately nuclear transcription factor associated-transactivation and
      transrepression. Activation of these intracellular signaling pathways may also
      modulate the process of miRNA maturation. Functionally, miRNAs may modulate
      epithelial immune responses at every step of the innate immune network, including
      production and release of cytokines/chemokines, expression of adhesion and
      costimulatory molecules, shuttling of miRNAs through release of exosomes and
      feedback regulation of immune homeostasis. Therefore, miRNAs act as critical
      regulators to the fine-tuning of epithelial immune responses.

PMID- 21725336
TI  - Bacterial physiology: MreB takes a back seat.

PMID- 21725337
TI  - Why do RNA viruses recombine?
AB  - Recombination occurs in many RNA viruses and can be of major evolutionary
      significance. However, rates of recombination vary dramatically among RNA
      viruses, which can range from clonal to highly recombinogenic. Here, we review
      the factors that might explain this variation in recombination frequency and show
      that there is little evidence that recombination is favoured by natural selection
      to create advantageous genotypes or purge deleterious mutations, as predicted if
      recombination functions as a form of sexual reproduction. Rather, recombination
      rates seemingly reflect larger-scale patterns of viral genome organization, such
      that recombination may be a mechanistic by-product of the evolutionary pressures
      acting on other aspects of virus biology.

PMID- 21725338
TI  - Dysphagia: Validation of a new nonradiological method for the prediction of
      ineffective swallowing.

PMID- 21725339
TI  - Hepatocellular carcinoma: Vitamin K2 does not prevent cancer recurrence.

PMID- 21725340
TI  - IBD: Evaluation of varicella immune status may be warranted in children with IBD.

PMID- 21725341
TI  - Liver: Modified interferon gamma targets key cells responsible for liver
      fibrogenesis.

PMID- 21725342
TI  - Pancreas: Blood urea nitrogen levels predict mortality risk in acute
      pancreatitis.

PMID- 21725343
TI  - IBD: CRP is a good long-term biomarker.

PMID- 21725345
TI  - Obesity: a step forward in understanding endoplasmic reticulum stress.

PMID- 21725346
TI  - Hepatitis C: Host receptor tyrosine kinases mediate HCV entry and are a promising
      new target for antiviral therapy.

PMID- 21725347
TI  - Primary sclerosing cholangitis: High-dose ursodeoxycholic acid is associated with
      risk of colonic neoplasia in patients with PSC and ulcerative colitis.

PMID- 21725348
TI  - Infection: Preventing 5 million child deaths from diarrhea in the next 5 years.

PMID- 21725349
TI  - Barrett esophagus: Treatment without histology--a dangerous affair.

PMID- 21725350
TI  - Hepatitis: Treatment failure in chronic hepatitis B.

PMID- 21725351
TI  - Liver transplantation: a simple inflammation marker predicts liver cancer
      prognosis.

PMID- 21725352
TI  - Recognition of CD146 as an ERM-binding protein offers novel mechanisms for
      melanoma cell migration.
AB  - Tumor cell migration is a well-orchestrated multistep process that drives cancer
      development and metastasis. Previous data indicated that CD146 expression
      correlates with malignant progression and metastatic potential of human melanoma
      cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell
      migration still remains poorly understood. Here, we report that CD146 physically
      interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM
      proteins to cell protrusions, promoting the formation and elongation of
      microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA
      activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide
      dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus
      sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and
      increased melanoma cell motility. CD146-activated RhoA also promotes further ERM
      phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5
      kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM
      association. Thus, our results provide a mechanistic basis to understand the role
      of CD146 in regulating human melanoma cell motility.

PMID- 21725354
TI  - Death-associated protein kinase increases glycolytic rate through binding and
      activation of pyruvate kinase.
AB  - Death-associated protein kinase (DAPk), a multi-domain serine/threonine kinase,
      regulates numerous cell death mechanisms and harbors tumor suppressor functions.
      In this study, we report that DAPk directly binds and functionally activates
      pyruvate kinase M2 (PKM2), a key glycolytic enzyme, which contributes to the
      regulation of cancer cell metabolism. PKM2 was identified as a novel binding
      partner of DAPk by a yeast two-hybrid screen. This interaction was validated in
      vitro by enzyme-linked immunosorbent assay using purified proteins and in vivo by
      co-immunoprecipitation of the two endogenous proteins from cells. In vitro
      interaction with full-length DAPk resulted in a significant increase in the
      activity of PKM2. Conversely, a fragment of DAPk harboring only the functional
      kinase domain (KD) could neither bind PKM2 in cells nor activate it in vitro.
      Indeed, DAPk failed to phosphorylate PKM2. Notably, transfection of cells, with a
      truncated DAPk lacking the KD, elevated endogenous PKM2 activity, suggesting that
      PKM2 activation by DAPk occurs independently of its kinase activity. DAPk
      transfected cells displayed changes in glycolytic activity, as reflected by
      elevated lactate production, whereas glucose uptake remained unaltered. A mild
      reduction in cell proliferation was detected as well in these transfected cells.
      Altogether, this work identifies a new role for DAPk as a metabolic regulator,
      suggesting the concept of direct interactions between a tumor suppressor and a
      key glycolytic enzyme to limit cell growth. Moreover, the work documents a unique
      function of DAPk that is independent of its catalytic activity and a novel
      mechanism to activate PKM2 by protein-protein interaction.

PMID- 21725353
TI  - Endogenous modulators and pharmacological inhibitors of histone deacetylases in
      cancer therapy.
AB  - The class-I histone deacetylases (HDACs) HDAC1 and HDAC2 belong to a family of 11
      zinc-dependent human HDACs and are overexpressed in many cancers. Inhibitors of
      these HDACs now in clinical trials show activity against several types of
      cancers. This review is focused on recent advances in both clinical and
      preclinical efforts to understand the basis for the actions of HDACis, with
      emphasis on implications for rational combinations with conventional or other
      targeted agents. We will address new perspectives on the molecular mechanisms by
      which HDACs act and how these actions relate to cancer. We will also review new
      evidence showing that HDACs are direct intracellular targets of the potent
      sphingolipid mediator S1P, the first identified endogenous nuclear regulator of
      these enzymes, linking sphingolipid metabolism in the nucleus to remodeling of
      chromatin and epigenetic regulation of gene expression. Understanding how
      endogenous molecules regulate HDAC activity in vivo may facilitate the search for
      safer and more effective anticancer drugs capable of interfering with HDAC
      functions in a highly specific manner.

PMID- 21725355
TI  - Neutralization of the gamma-secretase activity by monoclonal antibody against
      extracellular domain of nicastrin.
AB  - Several lines of evidence suggest that aberrant Notch signaling contributes to
      the development of several types of cancer. Activation of Notch receptor is
      executed through intramembrane proteolysis by gamma-secretase, which is a
      multimeric membrane-embedded protease comprised of presenilin, nicastrin (NCT),
      anterior pharynx defective 1 and PEN-2. In this study, we report the
      neutralization of the gamma-secretase activity by a novel monoclonal antibody
      A5226A against the extracellular domain of NCT, generated by using a recombinant
      budded baculovirus as an immunogen. This antibody recognized fully glycosylated
      mature NCT in the active gamma-secretase complex on the cell surface, and
      inhibited the gamma-secretase activity by competing with the substrate binding in
      vitro. Moreover, A5226A abolished the gamma-secretase activity-dependent growth
      of cancer cells in a xenograft model. Our data provide compelling evidence that
      NCT is a molecular target for the mechanism-based inhibition of gamma-secretase,
      and that targeting NCT might be a novel therapeutic strategy against cancer
      caused by aberrant gamma-secretase activity and Notch signaling.

PMID- 21725356
TI  - Consequences of DJ-1 upregulation following p53 loss and cell transformation.
AB  - p53 is a tumor suppressor that responds to various stress signals by initiating
      cell-cycle arrest, senescence and apoptosis. Mutations of the p53 gene are found
      in over 50% of human tumors, highlighting the importance of p53 in tumor
      suppression. Numerous studies have reported on the interactions between p53, IGF
      1-AKT and mTOR pathways as potentially explaining some of the tumor suppressive
      activities of p53. To further understand the basis of these interactions, we
      analyzed the involvement of DJ-1, an oncogene known to drive AKT-mediated cell
      survival, in the p53-AKT axis. In this study, we show that DJ-1 and p53 are
      tightly 'linked': p53 prevents the accumulation of DJ-1 protein, whereas loss of
      p53 leads to stabilization and enhancement of DJ-1 expression. Interestingly,
      this increase in DJ-1 level is only observed when p53 loss is accompanied by
      transformation of cells. Moreover, DJ-1 seems to be required for the enhanced
      activation of AKT observed in p53-deficient cells. Such observation confers a new
      property to DJ-1 associated to transforming-process to its oncogenic ability to
      drive AKT activation. We also show that DJ-1 is necessary for p53 activation
      following oxidative stress, suggesting the existence of a finely regulated loop
      between these two proteins in transformed cells. Finally, we demonstrate that in
      the absence of p53, DJ-1 is stabilized by ROS accumulation, and surprisingly
      seems to be required for this high intracellular ROS production. These data offer
      new insights into the regulation of DJ-1 and suggest that DJ-1 is a target of
      p53. Importantly, our study highlights that during transformation, DJ-1 is having
      a key role in the p53-regulated AKT pathway and p53-driven oxidative-stress
      response.

PMID- 21725357
TI  - MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63.
AB  - MYCN amplification is a major biomarker of poor prognosis, occurring in 25-30% of
      neuroblastomas. MYCN has contradictory roles in promoting cell growth and
      sensitizing cells to apoptosis. We have recently shown that p53 is a direct
      transcriptional target of MYCN in neuroblastoma and that p53-mediated apoptosis
      may be an important mechanism of MYCN-induced apoptosis. Although p53 mutations
      are rare in neuroblastoma at diagnosis, the p53/MDM2/p14(ARF) pathway is often
      inactivated through MDM2 amplification or p14(ARF) inactivation. We hypothesized
      that reactivation of p53 by inhibition of its negative regulator MDM2, using the
      MDM2-p53 antagonists Nutlin-3 and MI-63, will result in p53-mediated growth
      arrest and apoptosis especially in MYCN-amplified cells. Using the SHEP Tet21N
      MYCN-regulatable system, MYCN(-) cells were more resistant to both Nutlin-3 and
      MI-63 mediated growth inhibition and apoptosis compared with MYCN(+) cells and
      siRNA-mediated knockdown of MYCN in four MYCN-amplified cell lines resulted in
      decreased p53 expression and activation, as well as decreased levels of apoptosis
      following treatment with MDM2-p53 antagonists. In a panel of 18 neuroblastoma
      cell lines treated with Nutlin-3 and MI-63, the subset amplified for MYCN had a
      significantly lower mean GI(50) value (50% growth inhibition) and increased
      caspase 3/7 activity compared with the non-MYCN-amplified group of cell lines,
      but p53 mutant cell lines were resistant to the antagonists regardless of MYCN
      status. We conclude that amplification or overexpression of MYCN sensitizes
      neuroblastoma cell lines with wild-type p53 to MDM2-p53 antagonists and that
      these compounds may therefore be particularly effective in treating high-risk
      MYCN-amplified disease.

PMID- 21725358
TI  - The SRC-associated protein CUB Domain-Containing Protein-1 regulates adhesion and
      motility.
AB  - Multiple SRC-family kinases (SFKs) are commonly activated in carcinoma and appear
      to have a role in metastasis through incompletely understood mechanisms. Recent
      studies have shown that CDCP1 (CUB (complement C1r/C1s, Uegf, Bmp1) Domain
      Containing Protein-1) is a transmembrane protein and an SRC substrate potentially
      involved in metastasis. Here we show that increased SFK and CDCP1 tyrosine
      phosphorylation is, surprisingly, associated with a decrease in FAK
      phosphorylation. This appears to be true in human tumors as shown by our
      correlation analysis of a mass spectrometric data set of affinity-purified
      phosphotyrosine peptides obtained from normal and cancer lung tissue samples.
      Induction of tyrosine phosphorylation of CDCP1 in cell culture, including by a
      mAb that binds to its extracellular domain, promoted changes in SFK and FAK
      tyrosine phosphorylation, as well as in PKC(TM), a protein known to associate
      with CDCP1, and these changes are accompanied by increases in adhesion and
      motility. Thus, signaling events that accompany the CDCP1 tyrosine
      phosphorylation observed in cell lines and human lung tumors may explain how the
      CDCP1/SFK complex regulates motility and adhesion.

PMID- 21725359
TI  - Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence
      in melanomas harboring (V600E)BRAF.
AB  - Identifying the spectrum of genetic alterations that cooperate with critical
      oncogenes to promote transformation provides a foundation for understanding the
      diversity of clinical phenotypes observed in human cancers. Here, we performed
      integrated analyses to identify genomic alterations that co-occur with oncogenic
      BRAF in melanoma and abrogate cellular dependence upon this oncogene. We
      identified concurrent mutational inactivation of the PTEN and RB1 tumor
      suppressors as a mechanism for loss of BRAF/MEK dependence in melanomas harboring
      (V600E)BRAF mutations. RB1 alterations were mutually exclusive with loss of
      p16(INK4A), suggesting that whereas p16(INK4A) and RB1 may have overlapping roles
      in preventing tumor formation, tumors with loss of RB1 exhibit diminished
      dependence upon BRAF signaling for cell proliferation. These findings provide a
      genetic basis for the heterogeneity of clinical outcomes in patients treated with
      targeted inhibitors of the mitogen-activated protein kinase pathway. Our results
      also suggest a need for comprehensive screening for RB1 and PTEN inactivation in
      patients treated with RAF and MEK-selective inhibitors to determine whether these
      alterations are associated with diminished clinical benefit in patients whose
      cancers harbor mutant BRAF.

PMID- 21725360
TI  - And-1 is required for the stability of histone acetyltransferase Gcn5.
AB  - Histone acetyltransferases (HATs) have a central role in the modification of
      chromatin as well as in the pathogenesis of a broad set of diseases including
      cancers. Gcn5 is the first identified transcription-related HAT that has been
      implicated in the regulation of diverse cellular functions. However, how Gcn5
      proteins are regulated remains largely unknown. Here we show that acidic
      nucleoplasmic DNA-binding protein (And-1, a high mobility group domain-containing
      protein) has remarkable capability to regulate the stability of Gcn5 proteins and
      thereby histone H3 acetylation. We find that And-1 forms a complex with both
      histone H3 and Gcn5. Downregulation of And-1 results in Gcn5 degradation, leading
      to the reduction of H3K9 and H3K56 acetylation. And-1 overexpression stabilizes
      Gcn5 through protein-protein interactions in vivo. Furthermore, And-1 expression
      is increased in cancer cells in a manner correlating with increased Gcn5 and
      H3K9Ac and H3K56Ac. Thus, our data reveal not only a functional link between Gcn5
      and And-1 that is essential for Gcn5 protein stability and histone H3
      acetylation, but also a potential role of And-1 in cancer.

PMID- 21725361
TI  - p140Cap suppresses the invasive properties of highly metastatic MTLn3-EGFR cells
      via impaired cortactin phosphorylation.
AB  - We have recently shown that the adaptor protein p140Cap regulates tumor
      properties in terms of cell motility and growth. Here, by using the highly
      metastatic rat adenocarcinoma cell line MTLn3-epidermal growth factor receptor
      (EGFR), we assess the role of p140Cap in metastasis formation. Orthotopic
      transplantation of MTLn3-EGFR cells over-expressing p140Cap in Rag2(-/-)gamma(c)(
      /-) mice resulted in normal primary tumor growth compared with the controls.
      Strikingly, p140Cap over-expression causes an 80% inhibition in the number of
      lung metastases. p140Cap over-expressing cells display a 50% reduction in
      directional cell migration, an increased number and size of focal adhesions, and
      a strong impairment in the ability to invade in a 3D matrix. p140Cap over
      expression affects EGFR signaling and tyrosine phosphorylation of cortactin in
      response to EGF stimulation. Intriguingly, p140Cap associates with cortactin via
      interaction with its second proline-rich domain to the cortactin SH3 domain. The
      phosphomimetic cortactin tyrosine 421 mutant rescues migration and invasive
      properties in p140Cap over-expressing cells. Taken together, these data
      demonstrate that p140Cap suppresses the invasive properties of highly metastatic
      breast carcinoma cells by inhibiting cortactin-dependent cell motility.

PMID- 21725362
TI  - FLASH is essential during early embryogenesis and cooperates with p73 to regulate
      histone gene transcription.
AB  - Replication-dependent histone gene expression is a fundamental process occurring
      in S-phase under the control of the cyclin-E/CDK2 complex. This process is
      regulated by a number of proteins, including Flice-Associated Huge Protein
      (FLASH) (CASP8AP2), concentrated in specific nuclear organelles known as HLBs.
      FLASH regulates both histone gene transcription and mRNA maturation, and its
      downregulation in vitro results in the depletion of the histone pull and cell
      cycle arrest in S-phase. Here we show that the transcription factor p73 binds to
      FLASH and is part of the complex that regulates histone gene transcription.
      Moreover, we created a novel gene trap to disrupt FLASH in mice, and we show that
      homozygous deletion of FLASH results in early embryonic lethality, owing to
      arrest of FLASH(-/-) embryos at the morula stage. These results indicate that
      FLASH is an essential, non-redundant regulator of histone transcription and cell
      cycle during embryogenesis.

PMID- 21725363
TI  - Functional differences among BRCA1 missense mutations in the control of
      centrosome duplication.
AB  - We analyzed the effects of 14 different missense mutations in the RING domain of
      BRCA1 on the function of the protein in the control of centrosome number in
      tissue culture cells. Whereas 2 of the 14 BRCA1 variant proteins were neutral in
      the centrosome duplication assay, missense mutations of zinc-coordinating
      residues (C24R, C27A, C39Y, H41F, C44F and C47G) and mutations encoding BRCA1
      variants M18T and I42V resulted in BRCA1 proteins that caused centrosome
      amplification. BRCA1 variant proteins I21V, I31M, L52F and D67Y had an
      intermediate effect on centrosome duplication. In addition, one of the variants,
      L52F, caused a peculiar phenotype with amplified centrosomes but the centrioles
      remained paired. By comparison, other BRCA1 variants that caused centrosome
      amplification had clustering of supernumerary centrosomes with unpaired
      centrioles. This surprising phenotype suggests that the BRCA1 protein regulates
      two functions in the control of centrosome duplication: regulation of centrosome
      number and regulation of centriole pairing. The L52F is unusual as it is
      defective in only one of these processes. This study analyzes the function of
      BRCA1 missense mutations in the control of centrosome duplication, a critical
      step in the maintenance of genetic stability of mammary epithelial cells, and
      indicates a new function of BRCA1 in the control of centriole pairing.

PMID- 21725364
TI  - The von Hippel-Lindau tumor suppressor protein regulates gene expression and
      tumor growth through histone demethylase JARID1C.
AB  - In clear-cell renal cell carcinoma (ccRCC), inactivation of the tumor suppressor
      von Hippel-Lindau (VHL) occurs in the majority of the tumors and is causal for
      the pathogenesis of ccRCC. Recently, a large-scale genomic sequencing study of
      ccRCC tumors revealed that enzymes that regulate histone H3 lysine 4
      trimethylation (H3K4Me3), such as JARID1C/KDM5C/SMCX and MLL2, were mutated in
      ccRCC tumors, suggesting that H3K4Me3 might have an important role in regulating
      gene expression and tumorigenesis. In this study we report that in VHL-deficient
      ccRCC cells, the overall H3K4Me3 levels were significantly lower than that of
      VHL+/+ counterparts. Furthermore, this was hypoxia-inducible factor (HIF)
      dependent, as depletion of HIF subunits by small hairpin RNA in VHL-deficient
      ccRCC cells restored H3K4Me3 levels. In addition, we demonstrated that only loss
      of JARID1C, not JARID1A or JARID1B, abolished the difference of H3K4Me3 levels
      between VHL-/- and VHL+/+ cells, and JARID1C displayed HIF-dependent expression
      pattern. JARID1C in VHL-/- cells was responsible for the suppression of HIF
      responsive genes insulin-like growth factor-binding protein 3 (IGFBP3), DNAJC12,
      COL6A1, growth and differentiation factor 15 (GDF15) and density-enhanced
      phosphatase 1. Consistent with these findings, the H3K4Me3 levels at the
      promoters of IGFBP3, DNAJC12, COL6A1 and GDF15 were lower in VHL-/- cells than in
      VHL+/+ cells, and the differences disappeared after JARID1C depletion. Although
      HIF2alpha is an oncogene in ccRCC, some of its targets might have tumor
      suppressive activity. Consistent with this, knockdown of JARID1C in 786-O VHL-/-
      ccRCC cells significantly enhanced tumor growth in a xenograft model, suggesting
      that JARID1C is tumor suppressive and its mutations are tumor promoting in ccRCC.
      Thus, VHL inactivation decreases H3K4Me3 levels through JARID1C, which alters
      gene expression and suppresses tumor growth.

PMID- 21725365
TI  - Sex differences in the GSK3beta-mediated survival of adherent leukemic
      progenitors.
AB  - Therapeutic resistance of acute myeloid leukemia stem cells, enriched in the
      CD34(+)38(-)123(+) progenitor population, is supported by extrinsic factors such
      as the bone marrow niche. Here, we report that when adherent onto fibronectin or
      osteoblast components, CD34(+)38(-)123(+) progenitors survive through an integrin
      dependent activation of glycogen synthase kinase 3beta (GSK3beta) by serine 9
      dephosphorylation. Strikingly, GSK3beta-mediated survival was restricted to
      leukemic progenitors from female patients. GSK3beta inhibition restored
      sensitivity to etoposide, and impaired the clonogenic capacities of adherent
      leukemic progenitors from female patients. In leukemic progenitors from female
      but not male patients, the scaffolding protein RACK1, activated downstream of
      alpha(5)beta(1)-integrin engagement, was specifically upregulated and controlled
      GSK3beta activation through the phosphatase protein phosphatase 2A (PP2A). In a
      mirrored manner, survival of adherent progenitors (CD34(+)38(-)) from male but
      not female healthy donors was partially dependent on this pathway. We conclude
      that the GSK3beta-dependent survival pathway might be sex-specific in normal
      immature population and flip-flopped upon leukemogenesis. Taken together, our
      results strengthen GSK3beta as a promising target for leukemic stem cell therapy
      and reveal gender differences as a new parameter in anti-leukemia therapy.

PMID- 21725366
TI  - Regulation of ovarian cancer progression by microRNA-187 through targeting
      Disabled homolog-2.
AB  - MicroRNAs (miRNAs) play important roles in tumorigenesis by regulating oncogenes
      and tumor-suppressor genes. In this study, miR-187 and miR-200a were found to be
      expressed at higher levels in ovarian cancers than in benign tumors. In patients
      with ovarian cancer, however, higher levels of miR-187 and miR-200a expression
      were paradoxically associated with better OS and recurrence-free survival.
      Further, multivariate analysis showed that miR-187 served as an independent
      prognostic factor for patients with ovarian cancer (n=176). Computational
      prediction and microarray results indicated that miR-187 directly targeted
      Disabled homolog-2 (Dab2), and luciferase reporter assays confirmed that the
      target site of miR-187 was located at the 3'-UTR of the Dab2 gene. Generally
      considered as a tumor-suppressor gene, Dab2 may actually promote tumor
      progression in advanced cancers through epithelial-to-mesenchymal transition
      (EMT). Ectopic expression of miR-187 in cancer cells promoted cell proliferation,
      but continued overexpression of miR-187 suppressed Dab2 and inhibited migration.
      Suppression of miR-187 upregulated Dab2, which, by inhibiting E-cadherin levels
      while stimulating vimentin and phospho-FAK levels, promoted EMT. Reduced ovarian
      cancer Dab2 histoscores correlated with high miR-187 levels and improved outcomes
      of patients. Collectively, these results demonstrate distinct dual roles of Dab2
      in cell proliferation and tumor progression. In the initial steps of
      tumorigenesis, upregulated miR-187 suppresses Dab2, promoting cell proliferation.
      During the later stages, however, continued increased levels of miR-187 inhibits
      the Dab2-dependent EMT that is associated with tumor invasiveness, which is
      presumed to be the reason why cancers with high miR-187 levels were associated
      with better survivals.

PMID- 21725367
TI  - Phosphoinositide 3-kinase signaling is critical for ErbB3-driven breast cancer
      cell motility and metastasis.
AB  - Many malignancies show increased expression of the epidermal growth factor (EGF)
      receptor family member ErbB3 (HER3). ErbB3 binds heregulin beta-1 (HRGbeta1) and
      forms a heterodimer with other ErbB family members, such as ErbB2 (HER2) or EGF
      receptor (EGFR; HER1), enhancing phosphorylation of specific C-terminal tyrosine
      residues and activation of downstream signaling pathways. ErbB3 contains six YXXM
      motifs that bind the p85 subunit of phosphoinositide 3 (PI3)-kinase. Previous
      studies demonstrated that overexpression of ErbB3 in mammary tumor cells can
      significantly enhance chemotaxis to HRGbeta1 and overall metastatic potential. We
      tested the hypothesis that ErbB3-mediated PI3-kinase signaling is critical for
      heregulin-induced motility, and therefore crucial for ErbB3-mediated invasion,
      intravasation and metastasis. The tyrosines in the six YXXM motifs on the ErbB3 C
      terminus were replaced with phenylalanine. In contrast to overexpression of the
      wild-type ErbB3, overexpression of the mutant ErbB3 did not enhance chemotaxis
      towards HRGbeta1 in vitro or in vivo. We also observed reduced tumor cell
      motility in the primary tumor by multiphoton microscopy, as well as a
      dramatically reduced ability of these cells to cross the endothelium and
      intravasate into the circulation. Moreover, whereas mutation of the ErbB3 C
      terminus had no effect on tumor growth, it had a dramatic effect on spontaneous
      metastatic potential. Treatment with the PI3-kinase inhibitor PIK-75 similarly
      inhibited motility and invasion in vitro and in vivo. Our results indicate that
      stimulation of the early metastatic steps of motility and invasion by ErbB3
      requires activation of the PI3-kinase pathway by the ErbB3 receptor.

PMID- 21725368
TI  - Regulated ATF5 loss-of-function in adult mice blocks formation and causes
      regression/eradication of gliomas.
AB  - Glioblastomas are among the most incurable cancers. Our past findings indicated
      that glioblastoma cells, but not neurons or glia, require the transcription
      factor ATF5 (activating transcription factor 5) for survival. However, it was
      unknown whether interference with ATF5 function can prevent or promote
      regression/eradication of malignant gliomas in vivo. To address this issue, we
      created a mouse model by crossing a human glial fibrillary acidic protein (GFAP)
      promoter-tetracycline transactivator mouse line with tetracycline operon-dominant
      negative-ATF5 (d/n-ATF5) mice to establish bi-transgenic mice. In this model, d/n
      ATF5 expression is controlled by doxycycline and the promoter for GFAP, a marker
      for stem/progenitor cells as well as gliomas. Endogenous gliomas were produced
      with high efficiency by retroviral delivery of platelet-derived growth factor
      (PDGF)-B and p53-short hairpin RNA (shRNA) in adult bi-transgenic mice in which
      expression of d/n-ATF5 was spatially and temporally regulated. Induction of d/n
      ATF5 before delivery of PDGF-B/p53-shRNA virus greatly reduced the proportion of
      mice that formed tumors. Moreover, d/n-ATF5 induction after tumor formation led
      to regression/eradication of detectable gliomas without evident damage to normal
      brain cells in all 24 mice assessed.

PMID- 21725369
TI  - MiR-200b and miR-15b regulate chemotherapy-induced epithelial-mesenchymal
      transition in human tongue cancer cells by targeting BMI1.
AB  - Chemotherapy has been reported to induce epithelial-mesenchymal transition (EMT)
      in tumor cells, which is a critical step in the process of metastasis leading to
      cancer spreading and treatment failure. However, the underlying mechanisms of
      chemotherapy-induced EMT remain unclear, and the involvement of microRNAs (miRNA)
      in this process is poorly understood. To address these questions, we established
      stable chemotherapy-resistant tongue squamous cell carcinoma (TSCC) cell lines
      CAL27-res and SCC25-res by exposing the parental CAL27 and SCC25 lines to
      escalating concentrations of cisplatin for 6 months. CAL27-res and SCC25-res
      cells displayed mesenchymal features with enhanced invasiveness and motility.
      MiRNA microarray illustrated that miR-200b and miR-15b were the most
      significantly downregulated microRNAs in CAL27-res cells. Ectopic expression of
      miR-200b and miR-15b with miRNA mimics effectively reversed the phenotype of EMT
      in CAL27-res and SCC25-res cells, and sensitized them to chemotherapy, but
      inhibition of miR-200b and miR-15b in the sensitive lines with anti-sense
      oligonucleotides induced EMT and conferred chemoresistance. Retrieving the
      expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a target for
      miR-200b and miR-15b, in the presence of the miRNA mimics by transfecting CAL27
      res cells with pcDNA3.1-BMI1-carrying mutated seed sequences of miR-200b or miR
      15b at its 3'-UTR recapitulated chemotherapy-induced EMT. In vivo, enforced miR
      200b or miR-15b expression suppressed metastasis of TSCC xenografts established
      by CAL27-res cells. Clinically, reduced miR-200b or miR-15b expression was
      associated with chemotherapeutic resistance in TSCCs and poor patient survival.
      Our data suggest that reduced expression of miR-200b and miR-15b underscores the
      mechanisms of chemotherapy-induced EMT in TSCC, and may serve as therapeutic
      targets to reverse chemotherapy resistance in tongue cancers.

PMID- 21725370
TI  - Growth hormone treatment impact on growth rate and final height of patients who
      received HSCT with TBI or/and cranial irradiation in childhood: a report from the
      French Leukaemia Long-Term Follow-Up Study (LEA).
AB  - The literature contains a substantial amount of information about factors that
      adversely influence the linear growth in up to 85% of patients undergoing
      haematopoietic SCT (HSCT) with TBI and/or cranial irradiation (CI) for acute
      leukaemia (AL). By contrast, only a few studies have evaluated the impact of
      growth hormone (GH) therapy on growth rate and final height (FH) in these
      children. We evaluated growth rates during the pre- and post-transplant periods
      to FH in a group of 25 children treated with HSCT (n=22), TBI (n=21) or/and CI
      (n=8) for AL and receiving GH therapy. At the start of GH treatment, the median
      height Z-score was -2.19 (-3.95 to 0.02), significantly lower than at AL
      diagnosis (P<0.001). Overall height gain from start of GH treatment to FH was
      0.59Z (-2.72 to 2.93) with a median height Z-score at FH of -1.35 (-5.35 to
      0.27). This overall height gain effect was greater in girls than in boys
      (P=0.04). The number of children with heights in the reference population range
      was greater after than before GH therapy (P=0.07). At FH the GVHD and GH
      treatments lasting <2 years were associated with shorter FH (P=0.02 and 0.05). We
      found a measurable beneficial effect of GH treatment on growth up to FH.

PMID- 21725371
TI  - Extramedullary relapse following allogeneic BMT in a postpartum female patient
      with acute lymphoblastic leukemia.

PMID- 21725372
TI  - A risk-based approach to optimize autologous hematopoietic stem cell (HSC)
      collection with the use of plerixafor.
AB  - Autologous hematopoietic stem cell (HSC) transplant is an effective treatment for
      patients with hematological malignancies. Unfortunately, 15-30% of patients fail
      to mobilize a sufficient number of HSCs for the transplant. Plerixafor is now
      used as a salvage mobilization regimen, with good success. We describe here a
      risk-based approach for the use of plerixafor, based on the circulating CD34(+)
      cell count and the CD34(+) cell dose collected after 4 days of G-CSF, that
      identifies potential poor HSC mobilizers upfront. A total of 159 patients
      underwent HSC collections using this approach. Of these, 55 (35%) were identified
      as high risk owing to low CD34(+) cell number or low yield on day 1 of
      collection, and received plerixafor on the subsequent days of collection. Of the
      159 patients, 151 (95%) were able to provide adequate collections with the first
      mobilization attempt in a median of 1.7 days using this approach. Of the eight
      who failed initial mobilization, 5 successfully underwent re-mobilization with
      plerixafor and G-CSF and 3 (1.9%) were mobilization failures. This approach
      helped to control the overall cost of HSC collections for our BMT program by
      decreasing the need for remobilization, reducing the number of collection days
      and avoiding the use of plerixafor in all patients.

PMID- 21725373
TI  - Predictors of health-related quality of life in patients treated with auto- and
      allo-SCT for hematological malignancies.
AB  - Identifying factors that predict health-related quality of life (QOL) following
      hematopoietic SCT, is important in estimating patients' abilities to adjust to
      the consequences of their disease and treatment. As the studies that have been
      published on this subject are scattered, the present study aimed to
      systematically review prognostic factors for health-related QOL after auto- and
      allo-SCT in hematological malignancies. A systematic, computerized search in
      Medline, EMBASE, PsycINFO and the Cochrane Library was conducted from 2002 to
      June 2010. The methodological quality of the studies was assessed using an
      adaptation of Hayden's criteria list. Qualitative data synthesis was performed to
      determine the strength of the scientific evidence. In all, 35 studies fulfilled
      the selection criteria. Strong-moderate evidence was found for GVHD, conditioning
      regimen, being female, younger age, receiving less social support and pre
      transplant psychological distress as predictors of various aspects of health
      related QOL following hematopoietic SCT. The results of this review may help
      transplant teams in selecting patients at risk for experiencing a diminished
      health-related QOL following hematopoietic SCT. Follow-up treatment can be
      provided in order to promote QOL.

PMID- 21725374
TI  - Autologous transplantation in CLL patients with B and C Binet stages: final
      results of the prospective randomized GOELAMS LLC 98 trial.
AB  - The relevance of high-dose chemotherapy followed by auto-SCT in CLL remains to be
      defined. The aim of the prospective, randomized, GOELAMS LLC 98 trial was to
      compare two strategies in previously untreated CLL patients aged <60 years.
      Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP
      followed by six CHOP courses in every 3 months in those achieving a complete or
      PR. Arm A was compared with high-dose therapy with auto-SCT (Arm B), used as
      consolidation after three CHOP courses in case of CR or very good PR. A total of
      86 patients were enrolled, of which 39 and 43 patients were evaluable in arm A
      and arm B, respectively. The primary endpoint was PFS. On an intent-to-treat
      basis and with a median follow-up time of 77.1 (range 1-135.5) months, the median
      PFS was 22 months in Arm A and 53 months in Arm B (P<0.0001). Median survival
      time was 104.7 months in arm A and 107.4 months in arm B. This trial demonstrates
      that frontline high-dose therapy with auto-SCT prolongs PFS but does not
      translate into a survival advantage in advanced CLL patients in the pre-rituximab
      era.

PMID- 21725375
TI  - Randomized study of early hospital discharge following autologous blood SCT:
      medical outcomes and hospital costs.
AB  - We report the first randomized study comparing early hospital discharge with
      standard hospital-based follow-up after high-dose chemotherapy (HDCT) and PBSCT.
      Patients aged 18-65 years, with an indication of PBSCT for non-leukemic malignant
      diseases were randomly assigned between two arms. Arm A consisted of early
      hospital discharge (HDCT during hospitalization, discharge at day 0, home stay
      with a caregiver, outpatient clinic follow-up). In arm B patients were followed
      up as inpatients. In total 131 patients were analyzed (66 in arm A and 65 in arm
      B). Patient characteristics and hematological reconstitution were comparable
      between the two groups. In arm A, 26 patients were actually discharged early.
      Patients in group A spent fewer days in hospital (11 vs 12 days, P=0.006). This
      strategy resulted in a 6% mean cost reduction per patient when compared with the
      conventional hospital-based group. The early discharge approach within the French
      health system, while safe and feasible, is highly dependent on social criteria
      (caregiver availability and home to hospital distance). It is almost always
      associated with conventional hospital readmission during the aplasia phase, and
      limits cost savings when considering the whole population of patients benefiting
      from HDCT in routine clinical practice.

PMID- 21725376
TI  - [What is established treatment?].

PMID- 21725377
TI  - [Ethical assessment when introducing new treatment].

PMID- 21725378
TI  - [Research on low dosage naltrexone].

PMID- 21725379
TI  - [Either--or, but both--also in stroke].

PMID- 21725380
TI  - [Fall out with Kant?].

PMID- 21725381
TI  - [Treat us as elderly pilots!].

PMID- 21725382
TI  - [Which test is best to diagnose genital chlamydia infection?].

PMID- 21725383
TI  - [The best in Norway--not always the best in the world].

PMID- 21725384
TI  - [Investigation in strongly suspected cancer].

PMID- 21725386
TI  - [Changed health requirements regarding driver's licence for people with
      epilepsy].

PMID- 21725387
TI  - [Treatment of idiopathic pulmonary arterial hypertension].
AB  - BACKGROUND: In the past 5-10 years, drug treatment of idiopathic pulmonary
      arterial hypertension has evolved considerably. Experience and results from use
      of such updated treatment in Norway has not been reported. MATERIAL AND METHOD:
      32 patients newly diagnosed with idiopathic pulmonary arterial hypertension, were
      consecutively assessed with respect to hemodynamics and physical capacity. The
      results after three months were compared with those after 12 months. Observed
      survival was compared with estimated survival from the time when only
      conventional treatment was available. RESULTS: The patients (78% women) were 42
      +/- 14 years, had dyspnea in NYHA class 2.9 +/- 0.4 and a maximal oxygen uptake
      of 12.0 +/- 3.9 ml/kg/min (37 +/- 13% of the expected). Updated treatment led to
      significantly improved hemodynamics and physical capacity, which persisted during
      follow-up. During 43 +/- 31 months follow-up, seven patients died while two
      underwent bilateral lung transplantation. Observed transplantation-free survival
      was 81% after one, two and three years, while that for estimated transplantation
      free survival was 70%, 58% and 49% respectively. INTERPRETATION: Treatment of
      idiopathic pulmonary arterial hypertension with updated treatment improves
      hemodynamics and thereby symptoms. Mortality remains high, but is probably lower
      than it was when only conventional treatment was available.

PMID- 21725388
TI  - [Percutaneous catheter-based implantation of artificial pulmonary valves in
      patients with congenital heart defects].
AB  - BACKGROUND: Percutaneous catheter-based implantation of artificial heart valves
      is a new technique that may supplement surgery and which may be used more in the
      future. We here report our first experience with implantation of artificial
      pulmonary valves in children with congenital heart defects. MATERIAL AND METHODS:
      Eligible patients were those with symptoms of heart failure combined with
      stenosis and/or insufficiency in an established artificial right ventricular
      outflow tract. The valve was inserted through a catheter from a vein in the groin
      or neck. Symptoms, echocardiography, invasive measurements and angiography were
      assessed for evaluation of treatment effect. Our treatment results are reported
      for the period April 2007-September 2009. RESULTS: Ten patients (seven men and
      three women, median age 17 years) were assessed. The procedure reduced pressure
      in the right ventricle (p = 0.008) and resolved the pulmonary insufficiency in
      all patients. The median time in hospital was two days. No patients had
      complications that were directly associated with the implantation procedure. One
      patient developed a pseudoaneurysm in the femoral artery, another had a short
      lasting fever two days after the procedure and one patient experienced a stent
      fracture that required surgery 9 months after the implantation. After 6 months
      all patients had a reduced pressure gradient in the right ventricular outflow
      tract (p = 0.008), the pulmonary insufficiency had improved (p = 0.006) and they
      all reported improval of symptoms. These results persisted for at least 24 months
      for the four patients who were monitored until then. INTERPRETATION: Percutaneous
      catheter-based implantation of artificial pulmonary valves improves hemodynamics
      in the right ventricle of selected patients with congenital heart defects. A
      randomized controlled study should be undertaken to provide a stronger evidence
      base for usefulness of this procedure.

PMID- 21725389
TI  - [Epilepsy and religion].
AB  - BACKGROUND: Throughout mankind's history, epilepsy has been perceived as a
      mysterious and supernatural disorder. People with epileptic seizures were seen
      either as demonic or holy. Here we present a survey of our current knowledge on
      the association between epilepsy and religion from a medical viewpoint. MATERIAL
      AND METHOD: The article is based on a non-systematic search of the database
      PubMed, biographies of Wise-Knut, and the authors' own experiences. RESULTS: A
      number of people with epilepsy, particularly those with temporal lobe epilepsy,
      have reported experiencing religious feelings during their seizures. Some
      experience a feeling of perfect harmony, the presence of God or a state of
      ecstasy. Insula is probably of importance for the seizure semiology. Postictally,
      some may develop religious delusions that can last for several days. A subgroup
      have an interictal personality characterized by a preoccupation with
      philosophical or religious questions, as well as hypergraphia. Wise-Knut, who
      lived in the 1800 s, is a well known example of this in Norway. There is now some
      evidence that a number of religious people, including prophets, saints, and cult
      founders, may have had temporal lobe seizures. INTERPRETATION: Using epilepsy as
      a model to explain spiritual experiences is controversial. However, temporal lobe
      epilepsy has probably influenced our religious and literary history more than has
      been previously acknowledged.

PMID- 21725390
TI  - [Epilepsy and depression].
AB  - BACKGROUND: Episodic depression is more prevalent among persons with epilepsy
      than among those without. In many of these patients, depressions affect the
      quality of life more severely than the seizures themselves. MATERIAL AND METHODS:
      The article is based on literature identified through a non-systematic search in
      PubMed, and the authors' own clinical experience with this patient group.
      RESULTS: Diagnosing depression in patients with epilepsy may be difficult,
      because the symptoms are somewhat atypical and appear episodically. Depressive
      symptoms may be temporally related to seizures (ictal or periictal), or more
      often - independent of them (interictal). The causes may be of neurobiological,
      psychosocial or iatrogenic nature. Patients who have temporolimbic epilepsy, a
      focus in the left hemisphere, and/or who take GABAergic drugs, seem to be
      particularly vulnerable. Antidepressants can in some cases reduce the seizure
      threshold, but SSRIs and SNRIs do this to little or negligible extent. These
      drugs are therefore recommended as first-line treatment for depression in
      patients with epilepsy. INTERPRETATION: There is a bidirectional relationship
      between epilepsy and depression, as both conditions increase the risk of
      developing the other. This phenomenon may be explained by accumulating evidence
      of pathophysiological mechanisms common to them both. Depression is frequently
      overlooked in patients with epilepsy, and accordingly not treated. We believe
      measures such as pharmacological treatment and/or cognitive, behavioral, and
      interpersonal therapy may improve the quality of life for these patients.

PMID- 21725391
TI  - [Schistosomiasis haematobium].

PMID- 21725392
TI  - [a woman with recurrence of venous and arterial thrombosis].
AB  - BACKGROUND: Hypercoagulability leading to arterial or venous thrombosis and
      embolism in patients with cancer is a known phenomenon. MATERIAL AND METHODS: We
      describe a 62 year old woman with a clinical course compatible with catastrophic
      antiphospholipid syndrome but seronegative findings and mucinous lung cancer. The
      case is discussed with reference to literature from a non-systematic PubMed
      search. RESULTS AND INTERPRETATION: Diagnoses of cerebral and cardiac infarcts,
      deep venous thrombosis and lung embolism led to a diagnosis of lung cancer by
      biopsy and positron emission tomography (PET). Early recurrence of venous and
      arterial thromboses or poor response to anticoagulation and antiplatelets should
      initiate cancer search in the assessment of such stroke patients. Especially the
      combination of venous and arterial thromboses should raise suspicion of cancer.
      PET and surgical cancer treatment should be evaluated at an early stage.

PMID- 21725393
TI  - [The diagnostic chasing].

PMID- 21725394
TI  - Subjectivity in certification of sick leave.

PMID- 21725395
TI  - [A small, corrupt old service--pharmacies and pharmacy law 2001].

PMID- 21725396
TI  - [Strait-jacket free psychiatry in Iceland].

PMID- 21725397
TI  - [Prayer during physician consultation?].

PMID- 21725399
TI  - Screening for colorectal cancer: taking New Zealand from 'among the worst' to
      'the best'?

PMID- 21725400
TI  - What influences recurrent presentations of older people to the emergency
      department?

PMID- 21725401
TI  - NZ Nurses Organisation comments on NZMA Health Equity Position Statement.

PMID- 21725402
TI  - Wood burning and air pollution.

PMID- 21725403
TI  - Toxicity of Christchurch wood smoke.

PMID- 21725404
TI  - Response to Kingham's editorial on air pollution.

PMID- 21725405
TI  - Relative risk according to the proportion of a population deemed to be at high
      risk after risk factor analysis.

PMID- 21725406
TI  - Ten-year dispensing trends of hypnotics in New Zealand.

PMID- 21725407
TI  - The Government's Goal for a Smokefree New Zealand by 2025: more decisions, and
      more detail, are urgently needed.

PMID- 21725408
TI  - "It's a small price to pay for life": faecal occult blood test (FOBT) screening
      for colorectal cancer, perceived barriers and facilitators.
AB  - AIM: To clarify perceptions influencing FOBT screening participation among the NZ
      European target population. METHOD: Participants (30 female, 20 male; 50-71
      years) recruited through urban (Auckland, Wellington, Christchurch) GP surgeries
      for in-depth, face-to-face interviews (digitally recorded and professionally
      transcribed verbatim). A pragmatic approach focused on aggregating transcript
      content. RESULTS: Participants believed early CRC lacked distinguishing signs and
      symptoms, but was treatable and suitable for screening, although slow development
      may undermine any sense of urgency. FOBT inaccuracies caused concern,
      particularly false negatives, but ongoing testing could reduce anxiety. Specimen
      collection was awkward, challenged social norms and individual squeamishness, but
      provided peace of mind, was painless, simple and private without high cost
      technological or professional involvement. Lacking preventive attitudes and
      experience of health responsibilities and screening, men were less likely to
      participate than women. CRC lacked public profile, highlighting government
      responsibility, before programme implementation, to resource high-profile
      education, largely through TV. General practitioner support and promotion was
      seen as critical. Inadequate health system capacity and resourcing was
      problematic. CONCLUSIONS: Despite challenging barriers, participants identified
      opportunities to increase FOBT screening participation, especially promotion to
      raise CRC profile, overcome perceived normative barriers and build self-efficacy.
      Adequate resourcing is essential to support appropriate promotion and timely
      programme delivery.

PMID- 21725409
TI  - The colorectal cancer patients' journey: the Auckland region.
AB  - AIM: To identify the time taken from referral to first treatment of patients with
      colorectal cancer (CRC) in the Auckland region and benchmark these against
      available guidelines for timeliness. METHOD: Retrospective study of clinical
      records of all patients diagnosed with CRC identified from the national registry
      and Auckland regional databases in the years 2001 and 2005. Data extracted
      included demographics, dates and types of interventions and the patient journey
      from referral to initiation of first treatment. RESULTS: Of the 1128 patients
      diagnosed and treated in these cohorts, 68% were referred through their general
      practitioner and 58% saw a surgeon at their first specialist appointment. Seventy
      nine percent received initial treatment with curative intent. The median time
      from initial referral to first treatment was 35 days, with only 68% of patients
      being treated within 62 days of initial referral. CONCLUSION: The colorectal
      patient journey is complicated by multiple pathways of presentation and treatment
      and by patient choice. These factors need to be considered when assessing the
      acceptability of transit times based on summary data. That nearly one-third of
      patients did not complete the United Kingdom-based target of 62 days from
      referral to first treatment indicates there is a need for further improvement in
      service delivery for patients developing CRC in the Auckland region.

PMID- 21725410
TI  - Chinese peoples' perceptions of colorectal cancer screening: a New Zealand
      perspective.
AB  - AIMS: A national cancer screening programme requires a level of perceived
      acceptability of the procedure among the target population groups to be
      successful (that is, achieve a high uptake rate). In this study we explored
      Chinese immigrants' attitudes and perceptions towards colorectal cancer
      screening. METHOD: A grounded theory methodology was used explore the
      determinants of colorectal cancer screening. In depth one-on-one interviews were
      conducted and subsequently analysed to develop an appreciation of the
      perspectives on colorectal cancer screening among Chinese people living in New
      Zealand. RESULTS: Findings indicated a high degree of perceived acceptability for
      the concept of a national colorectal cancer screening programme. Chinese
      participants valued health care and preventive health measures were highly
      prioritised. However, colorectal cancer suffered from the 'poor cousin' syndrome
      whereby other more highly publicised cancers, such breast cancer, or skin cancer,
      were perceived to be more relevant and serious, thus marginalising the perceived
      priority of colorectal cancer screening. Overall, participants paid close
      attention to their bodies' balance and were proactive in seeking medical advice.
      Patient practitioner interaction was also found to be influential in the
      patient's decision to seek screening. CONCLUSION: The results of the study
      suggest that the introduction of a colorectal cancer screening programme in New
      Zealand would benefit from close attention to cultural determinants of screening
      uptake to provide an equitable service and outcome. Chinese patients who are
      eligible for participating in the colorectal cancer screening would benefit from
      access to appropriately detailed and culturally relevant information on the
      risks, benefit and procedures associated with colorectal cancer screening.

PMID- 21725411
TI  - Gastric cancer location and histological subtype in Pacific people and Maori
      defies international trends.
AB  - AIMS: Gastric cancer location and histopathology in Pacific people (mostly of
      Samoan, Tongan, Niuean, or Cook Islands origin) and Maori in New Zealand has not
      been specifically examined. METHODS: A retrospective review of all histologically
      proven new cases of gastric adenocarcinoma and gastro-oesophageal adenocarcinoma
      at Middlemore Hospital (Auckland, New Zealand) from June 2003-June 2009 was
      conducted. Demographic data, clinical presentation, diagnostic/ staging
      investigations and surgical outcomes were recorded. RESULTS: There were 133
      patients of whom 79 (59%) were male. Forty-nine (37%) patients were of Pacific
      ethnicity and 34 (26%) were Maori. Maori (59.3 years; p=0.01) and Pacific (64.5
      years; p=0.01) patients were significantly younger at diagnosis compared to
      European patients (77.2 years). European patients had more proximal tumours
      (n=18; 47%) compared to Pacific (n=5; 10%) and Maori (n=4; 12%) patients (p=
      0.01). Pacific (n=25; 51%) and Maori (n=21; 62%) patients had a significantly
      higher percentage of diffuse-type gastric cancer compared to European (n=7; 18%)
      patients. There was no difference in stage of presentation between ethnic groups.
      CONCLUSIONS: Maori and Pacific patients present with gastric cancer at higher
      rates and at a younger age. They have a predominance of diffuse-type antral and
      gastric body cancers which stand in contrast to global trends in gastric cancer.

PMID- 21725412
TI  - Challenging differential diagnosis of a wild-type gastrointestinal stromal tumour
      (GIST) or rare reticular perineurioma of the stomach? The role for mutational
      analysis.
AB  - The differential diagnosis of submucosal stomach lesions includes
      gastrointestinal stromal tumour (GIST), leiomyoma, synovial sarcomas,
      perineurioma, myxoid chondrosarcoma, myoepithelial tumour and other rare
      mesenchymal tumours. GISTs are well-defined lesions with distinctive morphologic
      and histogenetic characteristics that show 95% positive staining for CD117.
      Differential diagnosis of wild-type GISTs can be challenging. Here, we present
      two stomach tumours that were operated on in our surgical department. Both
      presented with positive immunoreactivity for CD117. In one tumour, c-Kit mutation
      analysis demonstrated positivity of exon 11_c.1674_1676delGGT, thus confirming
      the diagnosis of a GIST. Mutational analysis of the second stomach lesion
      demonstrated negativity for all known c-KIT and PDGFRA exons. In situ
      hybridisation ruled out a synovial sarcoma. An additional immunohistochemical
      staining for epithelial membrane antigen eventually confirmed the diagnosis of an
      extremely rare reticular perineurioma in the stomach, so far reported for the
      second time worldwide. Both patients have not shown any signs of recurrence 2
      years after surgery. The presented cases emphasise the benefits of performing a
      mutational analysis in difficult GISTs, including wt-GISTs, and demonstrates the
      importance and challenges in differentiating GISTs from other mesenchymal
      tumours.

PMID- 21725413
TI  - Carcinoid tumours of the appendix in children in Auckland, New Zealand: 1965
      2008.
AB  - AIMS: Carcinoid tumours (CT) of the appendix are rare in children. The study aims
      to review paediatric CT of the appendix in Auckland and conduct a literature
      review. METHOD: Retrospective review of all CT of the appendix at the Auckland
      paediatric hospital from 1965 until 2008. Patients were identified from the
      Auckland Laboratory Pathology Department database. Patient charts and
      histopathological slides were reviewed when available. RESULTS: 47 children had a
      histologically confirmed CT of the appendix (34 females, 12 males). Mean age 12.3
      years (7-15 years). Mean tumour diameter 0.83 cm (range 0.1 cm-2.3 cm). 55%
      tumour diameter <1 cm. Two patients had tumour diameters >2 cm. Extent of
      invasion known in 38 patients. Four within appendiceal submucosa, 11 into
      muscularis, 15 into serosa and 8 cases tumour extended to mesoappendix. Suspected
      appendicitis was the indication for surgery in each case. 44 patients had
      appendicectomy only, 3 patients had right hemicolectomy with residual tumour in
      one specimen. Literature search revealed 88 studies of which 11 case series of CT
      of the appendix in children were compared to our own study. CONCLUSION: CT of the
      appendix in children are uncommon. Most will be cured by appendicectomy only.
      Recurrence and metastatic disease are rare. Mesoappendiceal invasion is not an
      absolute indication for further surgery.

PMID- 21725414
TI  - Frequent attenders at emergency departments: research regarding the utility of
      management plans fails to take into account the natural attrition of attendance.
AB  - AIM: To compare, over a 4-year period, a cohort of adult frequent attenders at
      Christchurch Hospital Emergency Department (Christchurch, New Zealand) who
      received case management with a cohort who did not. METHOD: A descriptive
      prospective cohort study of patients who attended ED 10 or more times during the
      index period of 1 Nov 2000-31 Oct 2001 was carried out. Each patient had an
      individual management plan. Attendance patterns were compared with a previous 4
      year study of patients without management plans which was performed in the same
      ED. This study acted as an historical control. RESULTS: 87 patients who met the
      criteria for frequent attendance were compared with 77 patients in the control
      group. 10 patients remained frequent users for all 4 years of the study, compared
      with 9 in the control group. Most patients attended less frequently in the second
      year, with attendance rates continuing to fall, while a small group continued to
      make frequent presentations. The percentage of the cohort still attending ED at
      least once a year in the 4th year was nearly identical in each study (65% in the
      control and 64% in the intervention group); the percentage of each cohort who
      remained as frequent attenders, still attending 10 or more times in the 4th year,
      was identical. CONCLUSIONS: This study showed similar rates of attrition in ED
      attendance between the cohorts with and without management plans. If there were
      not a 'control' group, the decline in attendance in the study group might have
      been attributed to the management plans. When attributing changes in attendance
      patterns to any intervention, it is important to be aware of natural attrition
      over time.

PMID- 21725415
TI  - Return visits to the emergency department and related hospital admissions by
      people aged 65 and over.
AB  - AIM: To describe the factors most commonly associated with re-presentation to the
      emergency department (ED) and related hospital admissions by those aged 65 years
      and over in one New Zealand district health board (DHB) region. METHODS:
      Computerised and paper-based records of 59 patients were examined. The sample was
      selected using proportionate stratified random sampling to ensure equivalent
      proportions of patients re-presenting to the tertiary hospital's ED and the
      secondary hospital's accident and medical department. RESULTS: Those who re
      presented to the ED within 3 months had an average of 3.4 comorbidities.
      Hypertension and ischaemic heart disease were the most common comorbidities.
      Abdominal pain, chest pain and shortness of breath were the most frequently
      presenting complaints. Patients were less likely (p=0.05) to re-present within 7
      days if their capacity to mobilise prior to presentation, and on discharge, was
      documented. Few patients were instructed to see their primary care provider
      within any given timeframe. CONCLUSION: Better documentation about changes in
      levels of function, both prior to presentation and on discharge, is needed to
      ensure that patients are physically able to manage at home. Specific
      interventions could be targeted to improve function if needs have been
      identified. The frequency of cardiovascular comorbidities and cardiac discharge
      diagnoses suggest that those aged 65 years and over re-present with an acute
      illness and not because of failure to cope at home. Findings support early
      primary healthcare follow-up since the majority of re-presentations occur within
      2 weeks.

PMID- 21725416
TI  - Pinnacle of life--Maori living to advanced age.
AB  - AIM: The purpose of this feasibility study was to investigate whether Maori of
      advanced age would be interested in and able to take part in a quantitative study
      involving a comprehensive questionnaire, physical health assessment and blood
      analyses (a range of biological markers). The study also aimed to involve older
      Maori in all stages: development of research questions, review of assessment
      techniques and interpretation of results. METHOD: Maori aged 75-79 years living
      in the Bay of Plenty and Lakes DHB areas were invited to participate in a
      feasibility study covering a wide range of quantitative health related questions.
      After informed consent interviews and physical assessments were conducted in
      participants' homes or at a local clinic by Maori health providers contracted as
      a research partner. For those who gave informed consent specifically for blood
      analyses, bloods were taken and analysed for defined biological markers of
      inflammation and ageing. All physical assessments and blood analyses were
      forwarded to each participant's own general practitioner and relevant guidance
      was given by the research team. RESULTS: Collective results from 33 Maori
      participants are presented and cover: Te Reo Maori me ona tikanga (Maori language
      and cultural knowledge), tribal and whanau (extended family) links, cultural
      values and religion, whanau engagement and recreational activities, health
      status, healthy eating and discrimination. The Te Whare Tapa Wha model of health
      and the Poutama model of human development are utilised to provide an overall
      framework and context to present the results in respect of our participants and
      to celebrate their 'advanced' old age. CONCLUSION: The feasibility study has been
      successful in engagement with older Maori. It has paved the way to implement a
      subsequent longitudinal study which aims to enrol 600 Maori aged 80 to 90 years
      and 600 non-Maori aged 85 years in the Bay of Plenty and Lakes District Health
      Board areas (Tauranga, Rotorua, Whakatane, Opotiki and Te Kaha). The longitudinal
      study, "Life and Living in Advanced Age, the cohort study in New Zealand LILACS
      NZ - Te Puawaitanga o Nga Tapuwae Kia Ora Tonu", will record and observe
      participants' journeys to the end of their life. The LILACS Study NZ is at the
      stage of recruitment of participants and funding has been allocated for waves two
      and three and the next stage of the study will have an increased focus on
      dementia.

PMID- 21725417
TI  - An unusual cause of abdominal pain.
AB  - We report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) (they
      are always alpha/beta) in a 36-year-old male who presented with a 6-week history
      of abdominal pain, fever and significant weight loss. Definitive diagnosis
      required a full thickness skin biopsy with PCR analysis for clonal T-cell gene
      arrangement. A literature search showed that SPTCL is a very rare cutaneous
      lymphoma limited to case reports.

PMID- 21725418
TI  - Medical image. Rupture of a benign mediastinal teratoma into left pleural space.

PMID- 21725419
TI  - Estimation-based approach for underwater image restoration.
AB  - For underwater image restoration, modeling of PSF relies on a priori knowledge of
      the inherent optical properties under water. But full knowledge-based restoration
      could be corrupted by the complexity and instability of the application
      environments. Concerned with representation of the backscattering noise of
      underwater image, this Letter proposes a simplified multilayer transfer model to
      formulate both the point spread function and the statistics of backscattering
      noise explicitly. Consequently, the parameters for image restoration are
      estimated from in situ measurement of the backscattering background without a
      priori knowledge of the inherent optical properties. The robust Wiener filter is
      applied to implement the restoration. Experimental results are presented.

PMID- 21725420
TI  - Stimulated Raman scattering microscopy by spectral focusing and fiber-generated
      soliton as Stokes pulse.
AB  - We demonstrate stimulated Raman microscopy with broadband pump and Stokes pulses,
      using spectral focusing to attain spectral resolution and to rapidly acquire
      spectra within a spectral window determined by the bandwidth of the pulses. As
      the Stokes pulse, we use the redshifted soliton generated in a photonic crystal
      fiber, which allows for simple shifting of the accessible spectral window.

PMID- 21725421
TI  - Holoscopy--holographic optical coherence tomography.
AB  - Scanning optical coherence tomography (OCT) is limited in sensitivity and
      resolution by the restricted focal depth of the confocal detection scheme.
      Holoscopy, a combination of holography and Fourier-domain full-field OCT, is
      proposed as a way to detect photons from all depths of a sample volume
      simultaneously with uniform sensitivity and lateral resolution, even at high NAs.
      By using the scalar diffraction theory, as frequently applied in digital
      holographic imaging, we fully reconstruct the object field with depth-invariant
      imaging quality. In vivo imaging of human skin is demonstrated with an image
      quality comparable to conventionally scanned OCT.

PMID- 21725422
TI  - Terahertz near-field imaging using subwavelength plasmonic apertures and a
      quantum cascade laser source.
AB  - The first demonstration, to our knowledge, of near-field imaging using
      subwavelength plasmonic apertures with a terahertz quantum cascade laser source
      is presented. "Bull's-eye" apertures, featuring subwavelength circular apertures
      flanked by periodic annular corrugations were created using a novel fabrication
      method. A fivefold increase in intensity was observed for plasmonic apertures
      over plain apertures of the same diameter. Detailed studies of the transmitted
      beam profiles were undertaken for apertures with both planarized and corrugated
      exit facets, with the former producing spatially uniform intensity profiles and
      subwavelength spatial resolution. Finally, a proof-of-concept imaging experiment
      is presented, where an inhomogeneous pharmaceutical drug coating is investigated.

PMID- 21725423
TI  - Coherent Raman scanning fiber endoscopy.
AB  - Coherent Raman scattering methods allow for label-free imaging of tissue with
      chemical contrast and high spatial and temporal resolution. However, their
      imaging depth in scattering tissue is limited to less than 1 mm, requiring the
      development of endoscopes to obtain images deep inside the body. Here, we
      describe a coherent Raman endoscope that provides stimulated Raman scattering
      images at seven frames per second using a miniaturized fiber scanner, a custom
      designed objective lens, and an optimized scheme for collection of scattered
      light from the tissue. We characterize the system and demonstrate chemical
      selectivity in mouse tissue images.

PMID- 21725424
TI  - "All air-plasma" terahertz spectroscopy.
AB  - We demonstrate terahertz wave generation and detection capabilities up to 6 THz
      without the need for solid state materials, biased electrodes, or forward
      propagating signal collection. An "all air-plasma" terahertz system is used to
      encode explosive material resonant signatures into the 357 nm nitrogen
      fluorescence line of a bichromatic field-induced laser plasma filament. These
      results show the practicability to extend these measurements to remote locations
      where terahertz pulse information is no longer limited by water vapor absorption,
      phonon resonance, or signal collection directionality.

PMID- 21725425
TI  - Efficient Tm:LuVO4 laser at 1.9 MUm.
AB  - We report an efficient laser-diode-pumped Tm-doped LuVO4 crystal laser at about
      1.9 MUm. For the first time to our knowledge, the pi-polarized Tm:LuVO4 laser was
      achieved. The maximum output power and slope efficiency were 1.32 W and 28.7%,
      respectively. By comparison, it has been found that the a-cut Tm:LuVO4 crystal
      should be more suitable for applications in high-power lasers. The central laser
      wavelength was observed to be located at about 1.9 MUm and shifted to shorter
      with the increase of intracavity light intensity, which could be explained based
      on the reabsorption of light in the Tm:LuVO4 crystal.

PMID- 21725426
TI  - Focusing light with a reflection photon sieve.
AB  - An advanced type of diffractive optical element is presented that combines the
      concept of the photon sieve with an off-axis, off-normal incidence reflection
      geometry. Compared to transmission optical elements, the signal-to-background
      ratio is significantly increased by separating the first from other diffraction
      orders without drastically reducing the size of the smallest diffractive element.
      The reflection photon sieve produces sharp foci at maximum contrast and offers
      the advantages of effective heat dissipation and a large working space above the
      focal plane. Experimental results for a device working at a photon energy of 100
      eV are presented and compared to theory.

PMID- 21725427
TI  - Laser diode pumped bismuth-doped optical fiber amplifier for 1430 nm band.
AB  - A 24 dB gain bismuth-doped fiber amplifier at 1430 nm pumped by a 65 mW
      commercial laser diode at 1310 nm is reported for the first time (to our
      knowledge). A 3 dB bandwidth of about 40 nm, a noise figure of 6 dB, and a power
      conversion efficiency of about 60% are demonstrated. The temperature behavior of
      the gain spectrum is examined.

PMID- 21725428
TI  - Single-layer one-dimensional nonpolarizing guided-mode resonance filters under
      normal incidence.
AB  - We demonstrate that properly designed one-dimensional guided-mode resonance
      filters (GMRFs) with only one grating layer can exhibit a nonpolarizing resonant
      filtering effect under normal incidence. A sinusoidal profile nonpolarizing GMRF
      is realized by photoinduced surface-relief grating formation on thin films of
      polymer-azobenzene complexes and subsequent atomic layer deposition, showing the
      feasibility of fabrication of such compact GMRFs.

PMID- 21725429
TI  - Enhanced magnetic response in a gold nanowire pair array through coupling with
      Bloch surface waves.
AB  - We numerically study the coupling of magnetic plasmon polaritons (MPPs) with
      Bloch surface waves (BSWs) in a system composed of a one-dimensional gold
      nanowire pair array lying on a periodic dielectric multilayer. At an appropriate
      period of the dielectric multilayer, maximum coupling takes place between the MPP
      and the BSW. It results in two branches of hybridized MPPs with a Rabi-type
      splitting as large as 125 meV. The maximal magnetic field intensity achieved in
      the center of nanowire pairs is enhanced greatly and an enhancement factor >1.5
      is observed compared with that achieved by a nanowire pair array lying directly
      on a substrate. This has potential applications in nonlinear optics and near
      field enhanced spectroscopy.

PMID- 21725430
TI  - Phase-shifting interferometry by wave amplitude modulation.
AB  - A new method for phase-shifting interferometry based on wave amplitude modulation
      is proposed and discussed. This proposal is based on the interference of three
      waves, where two waves attend as two reference waves and the other wave attends
      as a probe wave. Thereby, three interference terms are obtained, but because a
      phase difference of pi/2 between the two references is kept constant, one of the
      three terms will be dropped, while the two remaining will be put in quadrature.
      Under these conditions, the resulting pattern is mathematically modeled by an
      interferogram of two waves, where an additional phase is given by the amplitude
      variations of the reference waves. In this Letter, both a theoretical model and
      some numerical simulations are presented.

PMID- 21725431
TI  - Lattice models of nontrivial "optical spaces" based on metamaterial waveguides.
AB  - Metamaterials are being used to model various exotic "optical spaces" for such
      applications as novel lenses and cloaking. While most efforts are directed toward
      the engineering of continuously changing dielectric permittivity and magnetic
      permeability tensors, an alternative approach may be based on lattices of
      metamaterial waveguides. Here we demonstrate the power of the latter technique by
      presenting metamaterial lattice models of various four-dimensional spaces.

PMID- 21725432
TI  - Implications of complete coherence in the space-frequency domain.
AB  - It was shown not long ago that complete spatial coherence of light at a pair of
      points in the space-time domain may be interpreted as a manifestation of so
      called "statistical similarity" between the fluctuating field at the two points.
      In this Letter, we consider complete spatial coherence at a pair of points in the
      space-frequency domain and derive a condition that the field at those points must
      obey. We illustrate the usefulness of the condition by an example.

PMID- 21725433
TI  - Single shot phase contrast imaging using laser-produced Betatron x-ray beams.
AB  - Development of x-ray phase contrast imaging applications with a laboratory scale
      source have been limited by the long exposure time needed to obtain one image. We
      demonstrate, using the Betatron x-ray radiation produced when electrons are
      accelerated and wiggled in the laser-wakefield cavity, that a high-quality phase
      contrast image of a complex object (here, a bee), located in air, can be obtained
      with a single laser shot. The Betatron x-ray source used in this proof of
      principle experiment has a source diameter of 1.7 MUm and produces a synchrotron
      spectrum with critical energy E(c)=12.3+/-2.5 keV and 109 photons per shot in the
      whole spectrum.

PMID- 21725434
TI  - Depolarizing differential Mueller matrices.
AB  - The evolution of a polarized beam can be described by the differential
      formulation of Mueller calculus. The nondepolarizing differential Mueller
      matrices are well known. However, they only account for 7 out of the 16
      independent parameters that are necessary to model a general anisotropic
      depolarizing medium. In this work we present the nine differential Mueller
      matrices for general depolarizing media, highlighting the physical implications
      of each of them. Group theory is applied to establish the relationship between
      the differential matrix and the set of transformation generators in the Minkowski
      space, of which Lorentz generators constitute a particular subgroup.

PMID- 21725435
TI  - Bandgap guidance in hybrid chalcogenide-silica photonic crystal fibers.
AB  - We report a hybrid chalcogenide-silica photonic crystal fiber made by pressure
      assisted melt-filling of molten glass. Photonic bandgap guidance is obtained at a
      silica core placed centrally in a hexagonal array of continuous centimeters-long
      chalcogenide strands with diameters of 1.45 MUm. In the passbands of the
      cladding, when the transmission through the silica core is very weak, the
      chalcogenide strands light up with distinct modal patterns corresponding to Mie
      resonances. In the spectral regions between these passbands, strong bandgap
      guidance is observed, where the silica core transmission loss is 60 dB/cm lower.
      The pressure-assisted fabrication approach opens up new ways of integrating
      sophisticated glass-based devices into optical fiber circuitry with potential
      applications in supercontinuum generation, magneto-optics, wavelength selective
      devices, and rare-earth-doped amplifiers with high gain per unit length.

PMID- 21725436
TI  - Integrated fiber Michelson interferometer based on poled hollow twin-core fiber.
AB  - We propose an integrated fiber Michelson interferometer based on a poled hollow
      twin-core fiber. The Michelson interferometer can be used as an electro-optic
      modulator by thermal poling one core of the twin-core fiber and introducing
      second-order nonlinearity in the fiber. The proposed fiber Michelson
      interferometer is experimentally demonstrated under driving voltages at the
      frequency range of 149 to 1000 Hz. The half-wave voltage of the poled fiber is
      135 V, and the effective second-order nonlinear coefficient chi2 is 1.23 pm/V.

PMID- 21725437
TI  - Creating very slow optical gap solitons with a grating-assisted coupler.
AB  - We show that optical gap solitons can be produced with velocities down to 4% of
      the group velocity of light using a grating-assisted coupler, i.e., a fiber Bragg
      grating that is linearly coupled to a non-Bragg fiber over a finite domain.
      Forward- and backward-moving light pulses in the non-Bragg fiber(s) that reach
      the coupling region simultaneously couple into the Bragg fiber and form a moving
      soliton, which then propagates beyond the coupling region. Two of these solitons
      can collide to create an even slower or stopped soliton.

PMID- 21725438
TI  - Phase-space tomography with a programmable Radon-Wigner display.
AB  - We show the adaptation of a multifunctional optical system consisting of two
      spatial light modulators for the optimal measurement of the Radon-Wigner
      transform of one-dimensional signals. The proposed Radon-Wigner display allows
      reconstructing the Wigner distribution and the phase or the mutual intensity of
      fully or partially coherent fields, respectively. It is also suitable for the
      analysis of two-dimensional rotationally symmetric or separable in Cartesian
      coordinates optical fields. The feasibility of the proposed scheme is
      experimentally demonstrated in several examples.

PMID- 21725439
TI  - Inverse problem approaches for stationary Fourier transform spectrometers.
AB  - A design of a miniaturized stationary Fourier transform IR spectrometer has been
      developed that produces a two-dimensional interferogram. The latter is disturbed
      by effects like parasitic interferences or disparities in the cutoff wavelength
      of the pixels. Thus, a simple Fourier transform cannot be used to estimate the
      spectrum of the scene. However, as these defects are deterministic, they can be
      measured and taken into account by inversion methods. A regularization term can
      also be added. The first experimental results prove the efficiency of this
      processing methodology.

PMID- 21725440
TI  - Metal-cavity surface-emitting microlaser with hybrid metal-DBR reflectors.
AB  - We demonstrate a metal-cavity surface-emitting microlaser at room temperature
      using hybrid metal/distributed Bragg reflectors as well as substrate removal. Our
      devices operate under continuous-wave current injection at room temperature. The
      smallest laser is 1.0 MUm in radius and ~4.0 MUm in height with a circular beam
      shape and an output over 8 MUW. The device lases at 995 nm wavelength with a
      threshold current of about 2.6 mA.

PMID- 21725441
TI  - Ultrafast and bias-free all-optical wavelength conversion using III-V-on-silicon
      technology.
AB  - Using a 7.5 MUm diameter disk fabricated with III-V-on-silicon fabrication
      technology, we demonstrate bias-free all-optical wavelength conversion for non
      return-to-zero on-off keyed pseudorandom bit sequence (PRBS) data at the speed of
      10 Gbits/s with an extinction ratio of more than 12 dB. The working principle of
      such a wavelength converter is based on free-carrier-induced refractive index
      modulation in a pump-probe configuration. We believe it to be the first bias-free
      on-chip demonstration of all-optical wavelength conversion using PRBS data. All
      optical gating measurements in the pump-probe configuration with the same device
      have revealed that it is possible to achieve wavelength conversion beyond 20
      Gbits/s.

PMID- 21725442
TI  - High-efficiency electrically tunable phase diffraction grating based on a
      transparent lead magnesium niobate-lead titanite electro-optic ceramic.
AB  - An electrically tunable high-efficiency phase diffraction grating using the
      transparent lead magnesium niobate-lead titanite (PMNT) electro-optic ceramic is
      proposed. A photomask technique is used for fabricating the grating with the
      Ti/Pt/Au interdigital electrodes. With the variation of the equivalent phase face
      induced by the quadratic electro-optic effect of the PMNT ceramic, the
      diffraction patterns of the light beam will be changed in which the diffraction
      efficiency may be controlled by an applied DC voltage. When the applied voltages
      are 41, 80, and 139 V, the zero-order, first-order, or second-order diffraction
      lights will disappear in turn with about 100% diffraction efficiency. The
      proposed grating can be used as an electrically controlled switch in the laser
      beam modulation and scanning, especially for the application of the high-power
      laser systems.

PMID- 21725443
TI  - Yb:YAG Innoslab amplifier: efficient high repetition rate subpicosecond pumping
      system for optical parametric chirped pulse amplification.
AB  - We report on a Yb:YAG Innoslab laser amplifier system for generation of
      subpicsecond high energy pump pulses for optical parametric chirped pulse
      amplification (OPCPA) at high repetition rates. Pulse energies of up to 20 mJ (at
      12.5 kHz) and repetition rates of up to 100 kHz were attained with pulse
      durations of 830 fs and average power in excess of 200 W. We further investigate
      the possibility to use subpicosecond pulses to derive a stable continuum in a YAG
      crystal for OPCPA seeding.

PMID- 21725444
TI  - Multimode interference filter for tuning of a mode-locked all-fiber erbium laser.
AB  - We present a mode-locked all-fiber erbium laser that can be tuned in wavelength
      while in pulsed operation. A low-cost multimode interference bandpass filter
      based solely on standard fibers was employed in a sigma-shaped cavity design. By
      bending the fiber filter, the spectrum could be continuously shifted by up to
      11.6 nm without interrupting pulsed operation, and output powers of more than 3.3
      mW at pulse durations below 350 fs were achieved.

PMID- 21725445
TI  - Directional control of optical power in integrated InP/InGaAsP extended cavity
      mode-locked ring lasers.
AB  - We report on a passively mode-locked InP/InGaAsP multiple quantum well
      semiconductor ring laser that operates at a 20 GHz repetition rate and around
      1575 nm wavelength. The device has been realized using the active-passive
      integration technology in a standardized photonic integration platform. We
      demonstrate experimentally for the first time to our knowledge that the relative
      positioning of the amplifier and absorber in a monolithically integrated ring
      laser can be used to control the balance of power between counterpropagating
      fields in the mode-locked state. The directional power balance is verified to be
      in agreement with a model previously reported.

PMID- 21725446
TI  - Full-field and single-shot quantitative phase microscopy using dynamic speckle
      illumination.
AB  - We developed an off-axis quantitative phase microscopy that works for a light
      source with an extremely short spatial coherence length in order to reduce the
      diffraction noise and enhance the spatial resolution. A dynamic speckle wave
      whose coherence length is 440 nm was used as an illumination source. To implement
      an off-axis interferometry for a source of low spatial coherence, a diffraction
      grating was inserted in the reference beam path. In doing so, an oblique
      illumination was generated without rotation of the wavefront, which leads to a
      full-field and single-shot phase recording with improved phase sensitivity of
      more than a factor of 10 in comparison with coherent illumination. The spatial
      resolution, both laterally and axially, and the depth selectivity are
      significantly enhanced due to the wide angular spectrum of the speckle wave. We
      applied our method to image the dynamics of small intracellular particles in live
      biological cells. With enhanced phase sensitivity and speed, the proposed method
      will serve as a useful tool to study the dynamics of biological specimens.

PMID- 21725447
TI  - Photonic bandgap plasmonic waveguides.
AB  - A type of a plasmonic waveguide has been proposed featuring an "open" design that
      is easy to manufacture, simple to excite and offers convenient access to a
      plasmonic mode. Optical properties of photonic bandgap (PBG) plasmonic waveguides
      are investigated experimentally by leakage radiation microscopy and numerically
      using the finite element method confirming photonic bandgap guidance in a broad
      spectral range. Propagation and localization characteristics of a PBG plasmonic
      waveguide have been discussed as a function of the wavelength of operation,
      waveguide core size, and the number of ridges in the periodic reflector for
      fundamental and higher order plasmonic modes of the waveguide.

PMID- 21725448
TI  - Generation of an axially super-resolved quasi-spherical focal spot using an
      amplitude-modulated radially polarized beam.
AB  - An axially super-resolved quasi-spherical focal spot can be generated by focusing
      an amplitude-modulated radially polarized beam through a high numerical aperture
      objective. A method based on the unique depolarization properties of a circular
      focus is proposed to design the amplitude modulation. The generated focal spot
      shows a ratio of x:y:z=1:1:1.48 for the normalized FWHM in three dimensions,
      compared to that of x:y:z=1:0.74:1.72 under linear polarization (in the x
      direction) illumination. Moreover, the focusable light efficiency of the designed
      amplitude-modulated beam is 65%, which is more than 3 times higher than the
      optimized case under linear polarization and thus make the amplitude-modulated
      radial polarization beam more suitable for a wide range of applications.

PMID- 21725449
TI  - Complex modes and instability of full-vectorial beam propagation methods.
AB  - Full-vectorial beam propagation methods (FVBPMs) are widely used to model light
      waves propagating in high-index-contrast optical waveguides. We show that the
      paraxial FVBPM and wide-angle FVBPMs based on diagonal Pade approximants are
      analytically unstable for waveguides with complex modes. The instability cannot
      be removed by enlarging the computational domain, increasing the numerical
      resolution, or using perfectly matched layers, because the complex modes are
      highly confined around the waveguide core.

PMID- 21725450
TI  - Nonuniform ensembles of diverse resonances in one-dimensional layered media.
AB  - The transmission spectra perform huge fluctuations even in the mostly suitable
      one-dimensional localized multilayer system. Fluctuations of layer thicknesses
      will cause random resonances between light waves and layers. We reveal that the
      nonuniform ensembles of the resonances are the key for the fluctuations of
      transmission spectra. The transmission spectra of each stack of layers are
      numerically calculated through the transfer-matrix method.

PMID- 21725451
TI  - Polycrystalline silicon optical fibers with atomically smooth surfaces.
AB  - We investigate the surface roughness of polycrystalline silicon core optical
      fibers fabricated using a high-pressure chemical deposition technique. By
      measuring the optical transmission of two fibers with different core sizes, we
      will show that scattering from the core-cladding interface has a negligible
      effect on the losses. A Zemetrics ZeScope three-dimensional optical profiler has
      been used to directly measure the surface of the core material, confirming a
      roughness of only ~0.1 nm. The ability to fabricate low-loss polysilicon optical
      fibers with ultrasmooth cores scalable to submicrometer dimensions should
      establish their use in a range of nonlinear optical applications.

PMID- 21725452
TI  - High-power actively mode-locked sub-nanosecond Tm3+-doped silica fiber laser.
AB  - A diode-pumped actively mode-locked Tm3+-doped double-clad silica fiber laser
      providing up to 11.8 W of average output power and pulse widths in mode-locked
      operation of 38 ps at a repetition rate of 37.88 MHz is reported. Pulse energies
      of up to 314 nJ were obtained.

PMID- 21725453
TI  - Controlling high harmonics generation by spatial shaping of high-energy
      femtosecond beam.
AB  - We demonstrate controlled high-order harmonic generation in gas using high-energy
      femtosecond pulses (50 fs-50 mJ on target) by performing spatial shaping of the
      terrawatt fundamental laser beam. We have developed a two optical paths mirror
      that can withstand high power and shape the pump beam into a quasi-flat-top
      profile (super Gaussian) near focus. We observe clear signatures of the spatial
      shaping on the harmonic beam in terms of profile, divergence, level of signal,
      and spectrum. The harmonic generation in neon with a quasi-flat-top beam results
      in a broadband extreme UV beam with extremely low divergence (~340 MUrad).

PMID- 21725454
TI  - Ultrahigh sensitivity polarimetric strain sensor based upon D-shaped optical
      fiber and surface plasmon resonance technology.
AB  - An ultrahigh sensitivity polarimetric strain sensor is proposed based upon a four
      layer D-shaped optical fiber and surface plasmon resonance (SPR) technology. In
      contrast to existing SPR-based sensors, which are based on changes in the
      refractive index of the overlayer, the sensor proposed in this study is based on
      the change in the refractive index of the fiber core in response to the
      application of an axial load. Specifically, the phase difference between the P
      and S waves after passing through the sensor under SPR conditions is measured
      using a common-path heterodyne interferometer and is used to determine the
      corresponding change in the refractive index of the core, from which the strain
      is then inversely derived. The experimental results show that the sensitivity of
      the proposed sensor is around 2.19*104 deg/epsilon, i.e., degree/strain. By
      contrast, that of a conventional (non-SPR) polarimetric fiber sensor is just
      5.2*102 deg/epsilon. To the best of the authors' knowledge, the sensor proposed
      in this study represents the first reported attempt to exploit the refractive
      index change of the core of an SPR-based fiber sensor for strain measurement
      purposes.

PMID- 21725455
TI  - The Gouy phase of Airy beams.
AB  - The phase behavior of Airy beams is studied, and their Gouy phase is defined.
      Analytic expressions for the idealized, infinite-energy type beam are derived.
      They are shown to be excellent approximations for finite-energy beams generated
      under typical experimental conditions.

PMID- 21725456
TI  - Three-dimensional holographic lithography by an iterative algorithm.
AB  - We have applied an iterative algorithm for hologram design with multiple output
      image planes arranged in close proximity to create continuous patterns within an
      imaging volume. These holograms have been designed for photolithography on three
      dimensional surfaces. The influence of simulated image plane separation on the
      final image, and its suitability for lithography, is assessed. Results are
      presented and the most suitable case is demonstrated experimentally.

PMID- 21725457
TI  - Plasmonic wave plate based on subwavelength nanoslits.
AB  - We propose a quarter-wave plate based on nanoslits and analyze it using a
      semianalytical theory and simulations. The device comprises two nanoslits
      arranged perpendicular to one another where the phases of the fields transmitted
      by the nanoslits differ by lambda/4. In this way, the polarization state of the
      incident light can be changed from linear to circular or vice versa. The
      plasmonic nanoslit wave plate is thin and has a subwavelength lateral extent. We
      show that the predictions for the phase shift obtained from a semianalytical
      model are in very good agreement with simulations by the finite difference time
      domain method.

PMID- 21725459
TI  - In-plane plasmonic modes of negative group velocity in perforated waveguides.
AB  - Eigenmodes in a typical perforated metal-insulator-metal waveguide structure have
      been analyzed. It is shown that the lowest eigenmode originates from a plasmonic
      waveguide mode between metallic layers and has net negative group velocity on the
      lower branch under TM polarization. The negative group velocity is directly
      derived from the dispersion curve in the plane of in-plane wave number and photon
      energy, and is responsible for the negative refraction effect reported in fishnet
      metamaterials.

PMID- 21725458
TI  - Time-gating scheme based on a photodiode for single-photon counting.
AB  - A fast, simple, and low-cost optical time-gating scheme for counting single
      photons is presented. Its construction consists of a silicon photodiode connected
      in series with a 50 Omega resistor and that operates in the photoconductive mode.
      The temporal resolution at the FWHM of the photon counting system was measured to
      be 62 ps. The profile of a single-photon pulse measured with the counting system
      agreed well with analytical results. The system was also used to successfully
      resolve a pair of targets with 4 mm separation inside a highly scattering medium
      by the use of time-gated early-arriving photons.

PMID- 21725460
TI  - Low Earth orbit satellite-to-ground optical scintillation: comparison of
      experimental observations and theoretical predictions.
AB  - Scintillation measurements of a 1064 nm laser at a 5 kHz sampling rate were made
      by an optical ground station at the European Space Agency observatory in
      Tenerife, Spain while tracking a low Earth orbit satellite during the spring and
      summer of 2010. The scintillation index (SI), the variance of irradiance
      normalized to the square of the mean, and power spectra measurements were
      compared to theoretical predictions based on the Kolmogorov spectrum, the Maui3
      nighttime turbulence profile, weak scintillation finite-beam wave theory,
      included receiver, and source aperture averaging with no free-fitting parameters.
      Good agreement was obtained, not only for the magnitude of the observed
      fluctuations, but also for the corresponding elevation angle dependence and shape
      of the power spectra. Little variation was seen for the SI between daytime and
      nighttime links. For all elevation angles, ascending and descending, the observed
      scintillation over extensive regions of the atmosphere is consistent with log
      normal statistics. Additionally, it appears from the results presented here that
      the nighttime turbulence profile for the atmosphere above the observatory in
      Tenerife is similar to that above Haleakala in Maui, Hawaii.

PMID- 21725461
TI  - Superresolution-focal-volume induced 3.0 Tbytes/disk capacity by focusing a
      radially polarized beam.
AB  - This paper reports on the study of the superresolution volume of the focal spot
      by focusing a radially polarized beam. This feature is achieved by increasing the
      inner radius of a high NA annular objective to break the diffraction-limited
      volume of a focal spot. The application of this finding into two-photon induced
      three-dimensional optical data storage leads to an enhanced photoreduction
      threshold effect in recording. As such, multilayer subdiffraction optical
      recording is experimentally demonstrated with an equivalent capacity of 3.0
      Tbytes/disk.

PMID- 21725462
TI  - Zitterbewegung in the honeycomb photonic lattice.
AB  - The propagation of a wave packet in a honeycomb photonic lattice has been studied
      using the time-dependent wave packet dynamics. It is found that the wave packet,
      superposed from the positive and negative energy modes at the vicinity of the two
      inequivalent Dirac points, can transform into a double-ring structure, which is
      caused by the interference between the two positive and negative energy modes
      around the Dirac points and is closely related to the Zitterbewegung (ZB). Also,
      a possible way to detect the ZB effect is proposed in the honeycomb photonic
      lattice.

PMID- 21725463
TI  - Does the leakage radiation profile mirror the intensity profile of surface
      plasmon polaritons?: comment.
AB  - We comment on a recent paper [Opt. Lett.35, 1944 (2010)].

PMID- 21725465
TI  - Recovering the absolute phase maps of two fringe patterns with selected
      frequencies.
AB  - Phase unwrapping is an important and challenging issue in fringe pattern
      profilometry. In this Letter we propose an approach to recover absolute phase
      maps of two fringe patterns with selected frequencies. Compared to existing
      temporal multiple frequency algorithms, the two frequencies in our proposed
      algorithm can be high enough and thus enable efficient and accurate recovery of
      absolute phase maps. Experiment results are presented to confirm the
      effectiveness of the proposed technique.

PMID- 21725466
TI  - Impact of bias current distribution on the noise figure and power saturation of a
      multicontact semiconductor optical amplifier.
AB  - We present an experimental investigation of a multicontact semiconductor optical
      amplifier. This first-generation device allows for direct control of the carrier
      density profile along the length of the waveguide. This is used to control the
      device noise figure, with a minimum value of 5 dB observed at a gain of 15 dB for
      an optimum carrier density profile. The opposite carrier density profile results
      in an increase of the power saturation by 3 dB.

PMID- 21725467
TI  - Fundamental structure of Fresnel diffraction: natural sampling grid and the
      fractional Fourier transform.
AB  - Fresnel integrals corresponding to different distances can be interpreted as
      scaled fractional Fourier transformations observed on spherical reference
      surfaces. We show that by judiciously choosing sample points on these curved
      reference surfaces, it is possible to represent the diffracted signals in a
      nonredundant manner. The change in sample spacing with distance reflects the
      structure of Fresnel diffraction. This sampling grid also provides a simple and
      robust basis for accurate and efficient computation, which naturally handles the
      challenges of sampling chirplike kernels.

PMID- 21725468
TI  - Extreme nonlinear optical enhancement in chalcogenide glass fibers with deep
      subwavelength metallic nanowires.
AB  - A nanostructured chalcogenide-metal optical fiber is proposed. This hybrid
      nanofiber is embedded with a periodic array of triangular-shaped deep
      subwavelength metallic nanowires set up in a bowtie configuration. Our
      simulations show that the proposed nanostructured fiber supports a guided
      plasmonic mode enabling both subwavelength field confinement and extreme
      nonlinear light-matter interactions, much larger than a bare chalcogenide
      nanowire of comparable diameter. This is all achieved with less than 3% by volume
      of metal content.

PMID- 21725469
TI  - Dipole radiation near hyperbolic metamaterials: applicability of effective-medium
      approximation.
AB  - We investigate the radiation rate of a dipole in close proximity to a hyperbolic
      metamaterial and confirm that both the radiation rate and its fraction directed
      into the metamaterial are greatly increased compared to bulk dielectric or metal.
      However, we find that the homogenized effective-medium approach greatly
      overestimates the Purcell factor compared to metal-dielectric subwavelength
      multilayers with previously reported layer thicknesses.

PMID- 21725470
TI  - Broadband and highly efficient quadratic interactions in double-slot lithium
      niobate waveguides through phase matching.
AB  - We propose and study in detail a phase-matched quadratic optical interaction in a
      realizable 2D double-slot lithium niobate (LN) waveguide. As opposed to the
      single-slot waveguide, the field can be well confined in the nanometric nonlinear
      material, and it is also more flexible for birefringence and dispersion design.
      The proposed compact double-slot structure could not only achieve form
      birefringence phase matching but also effectively enhance the modal overlap
      integral and expand the working wavelength. The calculated results on second
      harmonic generation show an extremely large bandwidth of ~40 nm. The modal
      overlap integral up to 0.035 W(3/2)/V can be realized by optimizing the waveguide
      geometry, and it is much better than previous results on single-slot waveguides.
      Its temperature dependence is low--around 25  degrees C. The geometry is
      practical considering the current micromachining technique of LN.

PMID- 21725471
TI  - High-power all-fiber passively Q-switched laser using a doped fiber as a
      saturable absorber: numerical simulations.
AB  - We report a design for a power-scalable all-fiber passively Q-switched laser that
      uses a large mode area Yb-doped fiber as a gain medium adiabatically tapered to
      an unpumped single-mode Yb-doped fiber, which serves as a saturable absorber.
      Through the use of a comprehensive numerical simulator, we demonstrate a
      passively Q-switched 1030 nm pulsed laser with 14 ns pulse duration and 0.5 mJ
      pulse energy operating at 200 kHz repetition rate. The proposed configuration has
      a potential for orders of magnitude of improvement in both the pulse energies and
      durations compared to the previously reported result. The key mechanism for this
      improvement relates to the ratio of the core areas between the pumped inverted
      large mode area gain fiber and the unpumped doped single-mode fiber.

PMID- 21725472
TI  - Large negative lateral shifts due to negative refraction.
AB  - When a thin structure in which negative refraction occurs (a metallo-dielectric
      structure or a photonic crystal) is illuminated by a beam, the reflected and
      transmitted beam can undergo a large negative lateral shift. This phenomenon can
      be seen as an interferential enhancement of the geometrical shift and can be
      considered a signature of negative refraction.

PMID- 21725473
TI  - Self-focusing collapse distance in ultrashort pulses and measurement of nonlinear
      index.
AB  - We analyze the method of moving focus to determine the critical power for self
      focusing by means of numerical simulation and a semianalytical model. It is shown
      that the original interpretation of a moving focus experiment does not hold in
      general and that inclusion of defocusing effects due to free electrons is
      necessary to relate the measured data to critical power.

PMID- 21725474
TI  - Superresolution vibrational imaging by simultaneous detection of Raman and hyper
      Raman scattering.
AB  - We have developed a superresolution vibrational imaging method by simultaneous
      detection of Raman and hyper-Raman scattering. Raman and hyper-Raman images
      obtained with the same laser spot carry independent information on the sample
      spatial distribution, owing to different signal dependence (linear in Raman and
      quadratic in hyper-Raman) on the incident light intensity. This information can
      be quantitatively analyzed to recover the incident light intensity distribution
      at the focal plane. A superresolution vibrational image is then derived by the
      constrained deconvolution of the images by the obtained incident light intensity
      distribution. This method has been applied to a TiO2 nanostructure and the
      obtained superresolution image was compared with a scanning electron microscopy
      image. The spatial resolution achieved by the present method is evaluated to be
      160 nm, which is more than twice better than the diffraction limited resolution.

PMID- 21725475
TI  - Phase-shifted Bragg microstructured optical fiber gratings utilizing infiltrated
      ferrofluids.
AB  - Results are presented on the efficient spectral manipulation of uniform and
      chirped Bragg reflectors inscribed in microstructured optical fibers utilizing
      short lengths of ferrofluids infiltrated in their capillaries. The infiltrated
      ferrofluidic defects can generate either parasitic reflection notch features in
      uniform Bragg reflectors of up to 80% visibility and ~0.1 nm spectral shift or
      tunability of the bandwidth and strength reflection up to 100% when introduced
      into chirped gratings. Spectra are presented for different spatial positions and
      optical characteristics of the ferrofluidic section.

PMID- 21725476
TI  - Optimizing holographic data storage using a fractional Fourier transform.
AB  - We demonstrate a method to optimize the reconstruction of a hologram when the
      storage device has a limited dynamic range and a minimum grain size. The optimal
      solution at the recording plane occurs when the object wave has propagated an
      intermediate distance between the near and far fields. This distance corresponds
      to an optimal order and magnification of the fractional Fourier transform of the
      object.

PMID- 21725477
TI  - Dual-wavelength Nd:YAG crystal laser at 1074 and 1112 nm.
AB  - We reported an efficient laser-diode (LD) end-pumped CW dual-wavelength Nd:YAG
      crystal laser operating at 1074 and 1112 nm simultaneously, for the first time to
      our knowledge. The maximum output power was 3.15 W with an optical conversion
      efficiency of 23.6%. Considering the broad absorption of carbonylhemoglobin and
      hemoglobin located at about 538 and 555 nm, respectively, we proposed that this
      dual-wavelength laser is an important source for detecting carbon monoxide
      poisoning by simple frequency doubling.

PMID- 21725478
TI  - Raman-based distributed temperature sensor with 1 m spatial resolution over 26 km
      SMF using low-repetition-rate cyclic pulse coding.
AB  - We experimentally investigate the benefits of a new optical pulse coding
      technique for long-range, meter and submeter scale Raman-based distributed
      temperature sensing on standard single-mode optical fibers. The proposed scheme
      combines a low-repetition-rate quasi-periodic pulse coding technique with the use
      of standard high-power fiber lasers operating at 1550 nm, allowing for what we
      believe is the first long-range distributed temperature measurement over single
      mode fibers (SMFs). We have achieved 1 m spatial resolution over 26 km of SMF,
      attaining 3 degrees C temperature resolution within 30 s measurement time.

PMID- 21725479
TI  - Type-II superlattice dual-band LWIR imager with M-barrier and Fabry-Perot
      resonance.
AB  - We report a high performance long-wavelength IR dual-band imager based on type-II
      superlattices with 100% cutoff wavelengths at 9.5 MUm (blue channel) and 13 MUm
      (red channel). Test pixels reveal background-limited behavior with specific
      detectivities as high as ~5*1011 Jones at 7.9 MUm in the blue channel and ~1*1011
      Jones at 10.2 MUm in the red channel at 77 K. These performances were attributed
      to low dark currents thanks to the M-barrier and Fabry-Perot enhanced quantum
      efficiencies despite using thin 2 MUm absorbing regions. In the imager, the high
      signal-to-noise ratio contributed to median noise equivalent temperature
      differences of ~20 milli-Kelvin for both channels with integration times on the
      order of 0.5 ms, making it suitable for high speed applications.

PMID- 21725480
TI  - Magnetic field modulation of photonic bandgap on FeCo/NiO half-shell array.
AB  - FeCo/NiO half-shell arrays were fabricated based on the periodic monolayer
      polystyrene spheres. The two-dimensional magnetic periodic arrays form well
      defined photonic crystals with pronounced stop bands. Quite interestingly, it is
      found that the stop bands can be tuned by an external magnetic field. The
      underlying mechanism is attributed to the controllable dielectric constant of the
      magnetic FeCo film under an applied magnetic field. The results shown here may
      open up an avenue for magnetically tunable photonic crystal stop bands, which may
      be useful for the creation of new magneto-optical devices.

PMID- 21725481
TI  - Nematicon-nematicon interactions in a medium with tunable nonlinearity and fixed
      nonlocality.
AB  - We investigate the attractive interaction between spatial solitons in nematic
      liquid crystals with a tunable nonlinearity and a constant nonlocality. The
      experimental study, carried out by controlling the orientation of the optic axis
      via the electro-optic response, shows how the interactions depend on
      reorientation, in excellent agreement with a model accounting for the anisotropic
      nature of the dielectric.

PMID- 21725482
TI  - Array of planar plasmonic scatterers functioning as light concentrator.
AB  - In this Letter, the concept of transmit array antenna enabling light
      concentration in the near-IR region is explored. As for the elements of the
      transmit array, concentric loop scatterers are chosen due to their design
      flexibility and potential for providing high phase variation by changing the
      dimensions of the loops. Periodic behaviors of the concentric loop elements are
      obtained by means of the finite-difference time-domain method. Using these
      results, a transmit array configuration is designed, and a focused beam at a
      desired distance is achieved. To model the electromagnetic fields of the finite
      array, the field equivalence principle and proper dyadic Green's functions are
      applied.

PMID- 21725483
TI  - Percolation-enhanced generation of terahertz pulses by optical rectification on
      ultrathin gold films.
AB  - Emission of pulses of electromagnetic radiation in the terahertz range is
      observed when ultrathin gold films on glass are illuminated with femtosecond near
      IR laser pulses. A distinct maximum is observed in the emitted terahertz
      amplitude from films of average thickness just above the percolation threshold.
      Our measurements suggest that the emission is through a second-order nonlinear
      optical rectification process, enhanced by the excitation of localized surface
      plasmon hot spots on the percolated metal film.

PMID- 21725484
TI  - Femtosecond laser-induced blazed periodic grooves on metals.
AB  - In this Letter, we generate laser-induced periodic surface structures (LIPSSs) on
      platinum following femtosecond laser pulse irradiation. For the first time to our
      knowledge, we study the morphological profile of LIPSSs over a broad incident
      angular range, and find that the morphological profile of LIPSSs depends
      significantly on the incident angle of the laser beam. We show that LIPSS grooves
      become more asymmetric at a larger incident angle, and the morphological profile
      of LIPSSs formed at an incident angle over 55 degrees  eventually resembles that
      of a blazed grating. Our study suggests that the formation of the blazed groove
      structures is attributed to the selective ablation of grooves through the
      asymmetric periodic surface heating following femtosecond pulse irradiation. The
      blazed grooves are useful for controlling the diffraction efficiency of LIPSSs.

PMID- 21725485
TI  - High-power, continuous-wave, mid-infrared optical parametric oscillator based on
      MgO:sPPLT.
AB  - We report a stable, high-power, cw, mid-IR optical parametric oscillator using
      MgO-doped stoichiometric periodically poled LiTaO3 (MgO:sPPLT) pumped by a Yb
      fiber laser at 1064 nm. The singly resonant oscillator (SRO), based on a 30 mm
      long crystal, is tunable over 430 nm from 3032 to 3462 nm and can generate as
      much as 5.5 W of mid-IR output power, with >4 W of over 60% of the tuning range
      and under reduced thermal effects, enabling room temperature operation. Idler
      power scaling measurements at ~3.3 MUm are compared with an MgO-doped
      periodically poled LiNbO3 cw SRO, confirming that MgO:sPPLT is an attractive
      material for multiwatt mid-IR generation. The idler output at 3299 nm exhibits a
      peak-to-peak power stability better than 12.8% over 5 h and frequency stability
      of ~1 GHz, while operating close to room temperature, and has a linewidth of ~0.2
      nm, limited by the resolution of the wavemeter. The corresponding signal
      linewidth at 1570 nm is ~21 MHz.

PMID- 21725486
TI  - Control of light polarization by acousto-optic diffraction from leaky acoustic
      wave in LiNbO3.
AB  - The acousto-optic control of light polarization due to diffraction by leaky
      acoustic waves in ZX-LiNbO3 has been demonstrated. The randomly polarized light
      of 633 nm wavelength is converted by the anisotropic diffraction into two beams
      with mutually orthogonal polarizations, the relative intensities of which depend
      on the light incidence angle and acoustic frequency. Variation in acoustic
      frequency from 108 to 112 MHz rotates the polarization of the output optical beam
      by 90 degrees . The acousto-optic control is accomplished entirely by electronic
      means and can be applied for implementation of fast polarization converters.

PMID- 21725487
TI  - Three-field noise correlation via third-order nonlinear optical processes.
AB  - We report experimental observation of three-field noise correlation between two
      coexisting four-wave mixing (FWM) signals and the probe signal in a coherently
      prepared rubidium vapor system. The two FWM signals in a double-Lambda type quasi
      four-level atomic system are obtained in different directions via their
      respective phase-matching conditions and can be detected individually. These
      signals and the probe beam are found to be strongly correlated or anticorrelated
      with each other.

PMID- 21725488
TI  - Terahertz imaging through self-mixing in a quantum cascade laser.
AB  - We demonstrate terahertz (THz) frequency imaging using a single quantum cascade
      laser (QCL) device for both generation and sensing of THz radiation. Detection is
      achieved by utilizing the effect of self-mixing in the THz QCL, and,
      specifically, by monitoring perturbations to the voltage across the QCL, induced
      by light reflected from an external object back into the laser cavity. Self
      mixing imaging offers high sensitivity, a potentially fast response, and a
      simple, compact optical design, and we show that it can be used to obtain high
      resolution reflection images of exemplar structures.

PMID- 21725489
TI  - Ultrashort broadband polarization beam splitter based on an asymmetrical
      directional coupler.
AB  - An ultrashort polarization beam splitter (PBS) based on an asymmetrical
      directional coupler is proposed by utilizing the evanescent coupling between a
      strip-nanowire and a nanoslot waveguide. In order to be convenient for
      integration with other components, mode converters between the nanoslot waveguide
      and the strip-nanowire are introduced and merged into S-bends to achieve an
      ultracompact PBS. As an example a 6.9 MUm long PBS based on a silicon-on
      insulator platform is designed, and the length of the coupling region is as small
      as 1.3 MUm. Numerical simulations show that the present PBS has a very broad band
      (>160 nm) for an extinction ratio of >10 dB.

PMID- 21725490
TI  - Tailoring Cerenkov second-harmonic generation in bulk nonlinear photonic crystal.
AB  - We investigate theoretically the Cerenkov-type second-harmonic generation in two
      dimensional bulk nonlinear photonic crystal with longitudinal modulation of the
      chi((2)) nonlinearity. We show that in this scheme the Cerenkov radiation can be
      achieved simultaneously at multiple directions with comparable intensities. The
      angles of emission are controllable by the spatial modulation of the
      nonlinearity. We propose a design of the periodically poled domain pattern, which
      maximizes the efficiency of the second-harmonic emission.

PMID- 21725491
TI  - Nonlinear soliton matching between optical fibers.
AB  - In this Letter, we propose a generic nonlinear coupling coefficient,
      eta(NL)2=eta|gamma/beta2|(fiber2)/|gamma/beta2|(fiber1), which gives a
      quantitative measure for the efficiency of nonlinear matching of optical fibers
      by describing how a fundamental soliton couples from one fiber into another.
      Specifically, we use eta(NL) to demonstrate a significant soliton self-frequency
      shift of a fundamental soliton, and we show that nonlinear matching can take
      precedence over linear mode matching. The nonlinear coupling coefficient depends
      on both the dispersion (beta2) and nonlinearity (gamma), as well as on the power
      coupling efficiency eta. Being generic, eta(NL) enables engineering of general
      waveguide systems, e.g., for optimized Raman redshift or supercontinuum
      generation.

PMID- 21725492
TI  - Furnace chemical vapor deposition bismuth-doped silica-core holey fiber.
AB  - A bismuth-doped-pure-silica holey fiber is fabricated using a fiber preform made
      by the furnace chemical vapor deposition method. The spectroscopic properties of
      the fiber are studied, and laser action at lambda=1450 nm with an efficiency of
      12% is demonstrated.

PMID- 21725493
TI  - Human leukocyte antigen-G expression on dendritic cells induced by transforming
      growth factor-beta1 and CD4+ T cells proliferation.
AB  - BACKGROUND: During antigen capture and processing, mature dendritic cells (DC)
      express large amounts of peptide-MHC complexes and accessory molecules on their
      surface. DC are antigen-presenting cells that have an important role in tolerance
      and autoimmunity. The transforming growth factor-beta1 (TGF-Beta1) cytokine has a
      regulatory role on the immune and non-immune cells. The aim of this study is to
      evaluate the effect of TGF-Beta1 on the induction of human leukocyte antigen-G
      (HLA-G) expression on the DC which is derived from monocyte. METHODS: In this
      study, we evaluated the effect of TGF-Beta1 in induction HLA-G expression on the
      monocyte-derived DC by flowcytometry and then CD4+ T cell proliferative responses
      in the presence of DC-treated TGF-Beta1 was studied. RESULTS: The results of this
      study showed that DC bearing HLA-G down-regulated activation of CD4+ T cells and
      production of IL-6 and IL-17 in comparison with control (P<0.05). CONCLUSION: It
      is concluded that TGF-Beta1 has an important regulatory role in CD4+ T cell
      proliferation by increasing HLA-G on DC and these cells can probably prevent
      unexpected immune responses in vivo.

PMID- 21725494
TI  - The study of collagen immobilization on a novel nanocomposite to enhance cell
      adhesion and growth.
AB  - BACKGROUND: Surface properties of a biomaterial could be critical in determining
      biomaterial's biocompatibility due to the fact that the first interactions
      between the biological environment and artificial materials are most likely
      occurred at material's surface. In this study, the surface properties of a new
      nanocomposite (NC) polymeric material were modified by combining plasma treatment
      and collagen immobilization in order to enhance cell adhesion and growth.
      METHODS: NC films were plasma treated in reactive O2 plasma at 60 W for 120 s.
      Afterward, type I collagen was immobilized on the activated NC by a safe, easy,
      and effective one-step process. The modified surfaces of NC were characterized by
      water contact angle measurement, water uptake, scanning electron microscopy
      (SEM), and Fourier transformed infrared spectroscopy in attenuated total
      reflection mode (ATR-FTIR). Furthermore, the cellular behaviors of human
      umbilical vascular endothelial cells (HUVEC) such as attachment, growth and
      proliferation on the surface of the NC were also evaluated in vitro by optical
      microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test.
      RESULTS: The outcomes indicated that plasma treatment and collagen immobilization
      could improve hydrophilicity of NC. SEM micrograph of the grafted film showed a
      confluent layer of collagen with about 3-5 mum thicknesses. In vitro tests showed
      that collagen-grafted and plasma-treated surfaces both resulted in higher cell
      adhesion and growth state compared with untreated ones. CONCLUSION: Plasma
      surface modification and collagen immobilization could enhance the attachment and
      proliferation of HUVEC onto NC, and the method would be usefully applied to
      enhance its biocompatibility.

PMID- 21725495
TI  - Transient expression assay of Agamma-588 (A/G) mutations in the K562 cell line.
AB  - BACKGROUND: In the previous study, we have shown that the presence of A allele at
      position -588 in Agamma-globin gene was highly frequent and closely associated
      with fetal hemoglobin elevation among beta-thalassemia intermedia patients.
      Therefore, we decided to investigate whether this allele (A allele at -588) could
      result in an increase in Agamma-globin gene expression to ameliorate the severity
      of the disease in thalassemia patients. METHODS: Three constructs containing mu
      locus control region, Agamma-globin and beta-globin genes were designed and
      employed in the transient expression assay. The difference among constructs was
      in the promoter region of Agamma-globin gene (A and G alleles at -588). A
      construct with T to C base substitution at -175 of Agamma-globin, created by site
      directed mutagenesis, was selected as positive control. The K562 cell line was
      transfected with the above constructs. Subsequently, the expression of Agamma
      globin gene was determined by quantitative real-time reverse transcription-PCR.
      RESULTS: There was not a significant increase in the expression of Agamma-globin
      gene in the construct containing A allele comparing the one with G allele at 
      588. CONCLUSIONS: -588 (A>G) mutation does not play a major role in regulation of
      Agamma-globin gene, suggesting that other factors may be involved.

PMID- 21725496
TI  - Contribution of nitric oxide synthase (NOS) activity in blood-brain barrier
      disruption and edema after acute ischemia/reperfusion in aortic coarctation
      induced hypertensive rats.
AB  - BACKGROUND: Nitric oxide synthase (NOS) activity is increased during hypertension
      and cerebral ischemia. NOS inactivation reduces stroke-induced cerebral injuries,
      but little is known about its role in blood-brain barrier (BBB) disruption and
      cerebral edema formation during stroke in acute hypertension. Here, we
      investigated the role of NOS inhibition in progression of edema formation and BBB
      disruptions provoked by ischemia/reperfusion injuries in acute hypertensive rats.
      METHODS: Rats were made acutely hypertensive by aortic coarctation. After 7 days,
      the rats were randomly selected for the recording of carotid artery pressure, or
      regional cerebral blood flow (rCBF) using laser Doppler. Ishcemia induced by 60
      min middle cerebral artery occlusion (MCAO), followed by 12-h reperfusion. A
      single i.p. dose of L-NAME (1 mg/kg) was injected before MCAO. After evaluation
      of neurological disabilities, rats were slaughtered under deep anesthesia to
      assess cerebral infarction volume, edema, or BBB disruption. RESULTS: A 75-85%
      reduction in rCBF was occurred during MCAO which returned to pre-occluded levels
      during reperfusion. Profound neurological disabilities were evidenced after MCAO
      alongside with severe cerebral infarctions (628 +/- 98 mm3), considerable edema
      (4.05 +/- 0.52%) and extensive BBB disruptions (Evans blue extravasation, 8.46 +/
      2.03 mug/g). L-NAME drastically improved neurological disabilities, diminished
      cerebral infarction (264 +/- 46 mm3), reduced edema (1.49 +/- 0.47%) and BBB
      disruption (2.93 +/- 0.66 mug/g). CONCLUSION: The harmful actions of NOS activity
      on cerebral microvascular integrity are intensified by ischemia/reperfusion
      injuries during acute hypertension. NOS inactivation by L-NAME preserved this
      integrity and diminished cerebral edema.

PMID- 21725497
TI  - Anti-inflammatory effect of the epigallocatechin gallate following spinal cord
      trauma in rat.
AB  - BACKGROUND: Spinal cord injury (SCI) stimulates an inflammatory reaction that
      causes substantial secondary damage inside the injured spinal tissue. The purpose
      of this study was to determine the anti-inflammatory effects of epigallocatechin
      gallate (EGCG) on traumatized spinal cord. METHODS: Rats were randomly divided
      into four groups of 12 rats each as follow: sham-operated group, trauma group,
      and EGCG-treatment groups (50 mg/kg, i.p., immediately and 1 hour after SCI).
      Spinal cord samples were taken 24 hours after injury and studied for
      determination of myeloperoxidase (MPO) activity, histopathological assessment and
      immunohistochemistry of tumor necrosis factor-Alpha (TNF-Alpha), interleukin
      1Beta (IL-1Beta), Nitrotyrosine, inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), and poly(ADP-ribose) polymerase (PARP). RESULTS: The
      results showed that MPO activity was significantly decreased in EGCG-treatment
      groups. Attenuated TNF-Alphaalpha, IL-1Beta, Nitrotyrosine, iNOS, COX-2, and PARP
      expression could be detected in the EGCG treated rats. Also, EGCG attenuated
      myelin degradation. CONCLUSION: On the basis of these findings, we propose that
      EGCG may be effective in protecting rat spinal cord from secondary damage by
      modulating the inflammatory reactions.

PMID- 21725498
TI  - In vitro effect of lead, silver, tin, mercury, indium and bismuth on human sperm
      creatine kinase activity: a presumable mechanism for men infertility.
AB  - BACKGROUND: The aim of the present study was to investigate the in vitro effects
      of mercury (Hg+2), lead (Pb+2), silver (Ag+2), tin (Sn+2), bismuth (Bi+3) and
      indium (In+3) ions on sperm creatine kinase. METHODS: creatine kinase was
      isolated from human sperm homogenates after chromatography on a DEAE cellulose
      column. RESULTS: At 60 mug ml-1 metal concentration, 70% of the creatine kinase
      activity was inhibited by Hg+2, while at the same concentration, Pb+2, Ag+2,
      Sn+2, Bi+3 and In+3 caused 68%, 66.5%, 65.7%, 64.7% and 62.7% inhibition,
      respectively. All six metal ions displayed a competitive type of inhibition
      mechanism for the isolated creatine kinase as analyzed by Lineweaver-Burk plot.
      Ki values of Hg+2, Pb+2, Ag+2, Sn+2, Bi+3 and In+3 were calculated and 8.34 mM, 5
      mM, 4.54 mM, 3.45 mM, 3.12 mM and 2.63 mM values were obtained, respectively.
      CONCLUSION: All the studied metal ions, at levels of 60 mug ml-1, may reduce
      normal sperm metabolism by inhibition of sperm creatine kinase, which probably is
      an important cause of infertility in men. However, further investigations, as in
      vitro and in vivo, are needed to elucidate the exact mechanism of heavy metals on
      male reproductive functioning at the molecular level.

PMID- 21725499
TI  - Neuroprotective effect of exogenous melatonin on dopaminergic neurons of the
      substantia nigra in ovariectomized rats.
AB  - BACKGROUND: Melatonin has receptors in substantia nigra pars compacta (SNc) and
      regulates development of dopaminergic (DA) neurons. This study was undertaken to
      determine ability of melatonin to protect SNc dopaminergic neuron loss induced by
      estrogen deficiency in ovariectomized rats. METHODS: Female rats were randomized
      into four groups of seven each: control, ethanol sham, ovariectomy (ovx) and ovx
      with melatonin (ovx + m). In ovx, ovaries were removed. Ovx + m group was
      intraperitoneally injected with melatonin for 10 days, while the ethanol sham
      group received only ethanol. All rats were perfused with 4% paraformaldehyde,
      midbrains removed, fixed and paraffin embedded, then processed for Nissl and
      tyrosine hydroxylase staining (IHC). Ten sections of SNc in Nissl and IHC
      staining were analyzed in each animal, Nissl stained and tyrosine hydroxylase
      (TH) immunoreactive cells were counted in five experimental groups randomly. Data
      was analyzed using SPSS by ANOVA and t-test. Differences were considered
      significant for P<0.05. RESULTS: There was less cell number in ovx compared to
      control and ethanol sham groups significantly (P<0.001). The ovx + m group had
      more cells than the ovx group in the SNc significantly (P<0.001). Furthermore,
      there was significant decrease of TH positive cell number in the ovx group
      compared to control and ethanol sham groups (P<0.05). The number of TH
      immunoreactive cells was higher in ovx + m compared to the ovx group (P<0.05).
      CONCLUSION: These findings can be compared with human and used in clinical
      application for prevention of DA neuron death of SNc after ovariectomy.

PMID- 21725500
TI  - Neuropathological changes in brain cortex and hippocampus in a rat model of
      Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with
      progressive loss of cognitive abilities and memory loss. The aim of this study
      was to compare neuropathological changes in hippocampus and brain cortex in a rat
      model of AD. METHODS: Adult male Albino Wistar rats (weighing 250-300 g) were
      used for behavioral and histopathological studies. The rats were randomly
      assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For
      behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16
      days post-lesion. For histological studies, Nissl, modified Bielschowsky and
      modified Congo red staining were performed. The lesion was induced by injection
      of 4 muL of ABeta (1-40) into the hippocampal fissure. RESULTS: In the present
      study, ABeta (1-40) injection into hippocampus could decrease the behavioral
      indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused
      ABeta deposition in the hippocampus and less than in cortex. We observed the loss
      of neurons in the hippocampus and cerebral cortex and certain subcortical
      regions. Y-maze test and single-trial passive avoidance test showed reduced
      memory retention in AD group. CONCLUSION: We found a significant decreased
      acquisition of passive avoidance and alternation behavior responses in AD group
      compared to control and sham group (P<0.0001). Compacted amyloid cores were
      present in the cerebral cortex, hippocampus and white matter, whereas, scattered
      amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced
      neuronal density was indicated in AD group.

PMID- 21725501
TI  - Effect of Medicago sativa Mhb1gene expression on defense response of Arabidopsis
      thaliana plants.
AB  - Besides the previously described nitric oxide-detoxification activity we
      identified new features of class-1 non-symbiotic hemoglobin from Medicago sativa
      (Mhb1). Under in vitro conditions, using peroxidase in-gel activity assay, the
      Mhb1 protein was shown to possess also peroxidase-like activity. Due to this
      activity, in the presence of nitrite and hydrogen peroxide, the protein can
      mediate autonitration and nitration of other proteins at tyrosine residues, as
      revealed by tandem mass spectrometry and immune assay approaches. Mhb1 through
      its multifunctional activities can affect different components of signal
      transduction cascades operating during plant response to infections. This
      influence is manifested by Mhb1-mediated selective up-regulation of expression of
      certain pathogen inducible genes in Pseudomonas syringae infected Arabidopsis
      thaliana plants which overproduce Mhb1, as revealed by reverse transcription
      quantitative real-time PCR analysis. Changes in expression level of these genes
      can influence such processes as synthesis of secondary metabolites, protein
      degradation and biosynthesis of ethylene. They can also result in alteration of
      pathogen-induced defense response of Mhb1 transgenic plants.

PMID- 21725502
TI  - On the mode of integration of the thylakoid membrane protein cytochrome b(6) into
      cytoplasmic membrane of Escherichia coli.
AB  - In the stroma compartment, several pathways are used for
      integration/translocation of chloroplast proteins into or across the thylakoid
      membrane. In this study we investigated the mode of incorporation of the
      chloroplast-encoded cytochrome b(6) into the bacterial membrane. Cytochrome b(6)
      naturally comprises of four transmembrane helices (A,B,C,D) and contains two b
      type hemes. In the present study, mature cytochrome b(6) or constructed deletion
      mutants of cytochrome were expressed in E. coli cells. The membrane insertion of
      cytochrome b(6) in this bacterial model system requires an artificially added
      presequence that directs the protein to use an E. coli membrane-insertion
      pathway. This could be accomplished by fusion to maltose-binding protein (MBP) or
      to the bacterial Sec-dependent signal peptide (SSpelB). The integration of mature
      cytochrome b(6) into the bacterial cytoplasmic membrane by the Sec pathway has
      been reported previously by our group (Kroliczewski et al., 2005, Biochemistry,
      44: 7570). The results presented here show that cytochrome b(6) devoid of the
      first helix A can be inserted into the membrane, as can the entire ABCD. On the
      other hand, the construct devoid of helices A and B is translocated through the
      membrane into the periplasm without any effective insertion. This suggests the
      importance of the membrane-anchoring sequences that are likely to be present in
      only the A and B part, and it is consistent with the results of computational
      prediction which did not identify any membrane-anchoring sequences for the C or D
      helices. We also show that the incorporation of hemes into the truncated form of
      cytochrome b(6) is possible, as long as the B and D helices bearing axial ligands
      to heme are present.

PMID- 21725503
TI  - Recognising coeliac disease in Eastern Europe--the hidden epidemic in our midst?

PMID- 21725504
TI  - Post traumatic spreading of occult HCC-breaking inside subfrenic haematoma.

PMID- 21725505
TI  - Von Meyenburg complex in a bariatric patient.

PMID- 21725506
TI  - Changing patterns of serological testing for celiac disease in Latvia.
AB  - BACKGROUND AND AIMS: A number of recent guidelines have discouraged the use of
      the old anti-gliadin tests for the detection of celiac disease; tissue
      transglutaminase IgA (tTGA) and anti-endomysial (EMA) tests are recommended
      instead. Our aim was to evaluate how the current recommendations have been
      applied in real practice. The secondary aim was to evaluate the positivity rates
      provided by different test types. METHODS: We analyzed the number of celiac
      disease tests [anti-gliadin IgA (AGA), anti-gliadin IgG (AGG), tTGA and EMA]
      performed by the largest laboratory in Latvia. The analysis was performed on a
      yearly basis for the period between 2004 and 2009. Additionally, we analyzed the
      percentage of the positive test results for each of the tests. RESULTS: The
      number of patients being tested for celiac disease constantly increased, with the
      average annual growth of 16.1%; this trend was similar both in children and in
      adults. The majority of patients (62.6%) were tested with anti-gliadin tests
      only; 27.7% were tested with either tTGA or EMA, while 9.7% were tested by a
      combination of the above groups. There was a substantial difference in the
      positivity rates of the different tests from 0.94% for EMA to 21.8% for AGG.
      Substantial differences were also present between various manufacturers'
      products. CONCLUSION: The current guidelines and the published evidence on the
      proper use of serological tests for celiac disease have been slow to be applied
      in clinical practice; more intensive education campaigns and change in
      reimbursement systems could improve the situation. Nevertheless, more clinicians
      in Latvia are checking patients for celiac disease; this suggests an overall
      increased awareness.

PMID- 21725507
TI  - Correlation among standard endoscopy, narrow band imaging, and histopathological
      findings in the diagnosis of nonerosive reflux disease.
AB  - BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is caused by the
      reflux of gastric contents into the esophagus. Narrow band imaging (NBI)
      facilitates mucosal surface evaluation and may improve the endoscopic diagnosis
      of GERD. The diagnosis of GERD is based on the combination of clinical symptoms,
      endoscopic findings, and histological changes. In this study we aimed to show the
      differences between standard white light endoscopy and the NBI technique in
      squamo-columnar junction evaluation. We also evaluated the patients with NERD, as
      determined by standard white light endoscopy, using the NBI technique and
      histopathological mucosa examination (inflammation or normal mucosa). METHODS: A
      total of 60 subjects were recruited prospectively: 40 with nonerosive reflux
      disease (NERD) and 20 with erosive reflux disease (ERD). Patients were subjected
      to esophagogastroduodenoscopy and, in all of them, two biopsies were taken 2 cm
      above the esophagogastric junction. RESULTS: NBI was more sensitive than standard
      white light endoscopy in distinguishing normal endoscopic findings.
      Histopathological findings were more prevalent than the mucosal changes diagnosed
      by the standard white light endoscopy and NBI. CONCLUSION: NBI is more sensitive
      than white light endoscopy in detecting inflammation in NERD patients. However,
      histopathological evaluation is the most sensitive, therefore taking a biopsy
      will remain useful.

PMID- 21725508
TI  - Efficacy of 48-hour post-operative antibiotics prophylaxis for patients
      undergoing percutaneous endoscopic gastrostomy tube in preventing site infection.
AB  - BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) is an endoscopic procedure
      for placing a feeding tube into the stomach through the skin, primarily to avoid
      malnutrition. Malnutrition can increase the risk of wound infection, whose
      incidence can be decreased by using antibiotic prophylaxis. AIM: The purpose of
      our study was to evaluate the efficacy of a new antibiotic regimen in preventing
      acute post-PEG procedure complications. PATIENTS AND METHODS: Ninety-seven
      consecutive patients were put on combined antibiotic therapy of clindamycin 600
      mg and cefotaxime 1,000 mg every eight hours, starting with the insertion of the
      PEG tube and maintained for 48 hours. Pain/tenderness, leakage/drainage, bleeding
      fever, maximum white blood cells (WBC) count, pus/discharge, and PEG tube
      function were evaluated within 48 hours and 1 week from PEG insertion. RESULTS:
      Infection at the site of PEG insertion occurred in 3 cases (3.1%) within 48 hours
      and in 1 case (1.0%) within 7 days. Within 48 hours from the procedure, incidence
      of fever and increased WBC count was 10.3% and 9.3%, respectively, though at 7
      days all were resolved. Pain, leak, and bleeding at the site of PEG placement
      were prevalently mild within 48 hours (74.2%, 12.4%,13.4% of patients,
      respectively) and subsided within 7 days (2.1%, 0%, 0%). One case (1.0%) of minor
      antibiotic side effect occurred. Two patients died due to complications not
      related to the procedure. CONCLUSION: The combined use of short-term cefotaxime
      and clindamycin seems to be effective in reducing incidence of acute
      complications due to PEG placement without increasing side-effects.

PMID- 21725509
TI  - Endosonographic tumor staging for treatment decision in resectable gastric
      cancer.
AB  - BACKGROUND AND AIMS: Neoadjuvant preoperative chemotherapy is the standard of
      care in locally advanced resectable gastric cancer. Therefore, accurate
      locoregional staging is essential for treatment decision. EUS is believed to be
      the most performant diagnostic method for locoregional staging. However, it is
      questionable, if results from centers of excellence can be maintained in clinical
      routine. METHODS: We retrospectively analyzed the data of 62 resectable gastric
      cancers staged by EUS during routine clinical work-up. Preoperative variables
      (tumor size and site, histological differentiation) were compared with the
      postoperative pathology. RESULTS: 19 locally limited (T1-2, N0), and 43 locally
      advanced (T3-4, or N+ irrespective of T stage) were analyzed. The sensitivity of
      EUS for the detection of locally advanced disease was 93%, with a specificity of
      78%. CONCLUSIONS: Even in daily routine practice, differentiation of locally
      limited and advanced disease with EUS can be performed with high sensitivity and
      good specificity. Therefore, EUS is an essential part of the diagnostic procedure
      in patients with gastric cancer.

PMID- 21725510
TI  - Intravenous ibandronate or sodium-fluoride--a 3.5 years study on bone density and
      fractures in Crohn's disease patients with osteoporosis.
AB  - BACKGROUND AND AIM: Osteoporosis commonly afflicts Crohn's disease (CD) patients.
      Management remains unclear, with limited results for intravenous (i.v.)
      bisphosphonates and a follow-up longer than one year. Intravenous bisphosphonates
      bypass gastrointestinal-tract irritation offering an interesting alternative
      suitable for CD patients. We tested the long-term efficacy and safety of
      colecalciferol and calcium with sodium-fluoride or i.v. ibandronate for
      osteoporosis in CD. METHODS: 66 CD patients with lumbar osteoporosis (T-score<
      2.5) were randomized to receive colecalciferol (1000 IU), calcium-citrate (800
      mg) and intermittent sustained-release sodium-fluoride (50 mg) [groupA, n=33] or
      i.v. ibandronate (1 mg/3-monthly) [groupB, n=33]. Dual-energy X-ray
      absorptiometry of the lumbar-spine and right femur and X-rays of the spine were
      performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment
      included visual reading and quantitative morphometry of X-rays. RESULTS: 55
      (83.3%) patients completed at least the 1st year available for intention-to-treat
      (ITT) analysis, 42 (63.6%) completed the 2nd and 35 (53.0%) the 3rd year
      available for per-protocol analysis. Lumbar T-score increased by +0.23+/-0.43
      (95%CI: 0.057-0.407, p<0.05), +0.71+/-1.05 (95%CI: 0.193-1.232, p<0.001) and
      +0.73+/-0.82 (95%CI: 0.340-1.336, p<0.001) (group A), and +0.28+/-0.41 (95%CI:
      0.132-0.459, p<0.05), +0.43+/-0.55 (95%CI: 0.184-0.671, p<0.01) and +0.51+/-0.74
      (95%CI: 0.145-0.882, p<0.001) (group B) during 1.0, 2.25 and 3.5 years follow-up
      time. In 2.71 years of follow-up, with the ITT analysis, the lumbar T-score
      increased by +0.66+/-0.97 (group A, p<0.001) and +0.46+/-0.67 (group B, p<0.001).
      One vertebral fracture with sodium-fluoride was not enough to detect differences
      between groups and the study was not powered for this. Study medication was well
      tolerated and safe. CONCLUSIONS: Sodium-fluoride and i.v. ibandronate improved
      osteoporosis. Keeping in mind bisphosphonates as a standard of osteoporosis care
      that reduce fracture-rate, data we do not have for sodium-fluoride, CD patients
      with osteoporosis can be treated safely with i.v. ibandronate.

PMID- 21725511
TI  - Guide-wire versus conventional contrast cannulation of the common bile duct for
      the prevention of post-ERCP pancreatitis in patients with choledocholithiasis.
AB  - BACKGROUND: Inadvertent injection of a contrast agent into the pancreatic duct is
      an important contributor factor to post-ERCP pancreatitis. AIM: To compare the
      incidence of post-ERCP pancreatitis and the success rate of biliary cannulation
      using guide-wire cannulation or the standard contrast injection technique.
      METHODS: A total of 128 patients with choledocholithiasis who underwent either
      guide-were cannulation (n=70) or contrast injection (n=58) were retrospectively
      reviewed. Outcome measurements were post-ERCP pancreatitis and rate of successful
      common bile duct (CBD) cannulation. RESULTS: Three patients (4.3%) in the guide
      wire cannulation group and five patients (8.6%) in the contrast injection group
      had post-ERCP pancreatitis (p>0.05). Successful CBD cannulation was achieved in
      91.4% with guide-wire cannulation and in 88% with conventional contrast
      cannulation (p>0.05). CONCLUSION: Our study failed to show significant reduction
      in the rate of post-ERCP pancreatitis with the use of guide-wire, although there
      was a downward trend. The success rate of cannulation was comparable between the
      two techniques.

PMID- 21725512
TI  - Predictive factors for nonalcoholic steatohepatitis (NASH) in patients with
      nonalcoholic fatty liver disease (NAFLD).
AB  - AIMS: The aim of our study was to assess the clinical and biological parameters
      associated with Nonalcoholic steatohepatitis (NASH) and to establish the
      predictors of significant fibrosis in Nonalcoholic fatty liver disease (NAFLD)
      patients. METHODS: We correlated clinical and biochemical parameters with
      histological features (simple steatosis or steatohepatitis) in 97 patients with
      NAFLD admitted to the University Hospital Bucharest for persistently raised
      aminotransferase levels. The biochemical parameters included lipid profile,
      glucose, liver tests and insulin. The Homeostatic Metabolic Assesment (HOMA)
      index and the oxidative stress were also evaluated. Factors associated with NASH
      and severe fibrosis (F>==3) were identified using the Mann-Whitney U test and
      multivariate analysis. The overall validity was measured using the area under
      receiver operating characteristic curve (AUROC) with 95% CI. RESULTS: At
      univariate analysis, age, BMI, splenic longitudinal diameter (SLD), HOMA, gamma
      glutamyl transpeptidase, C- reactive protein (CRP), albumin and INR were
      significantly associated with histologically proven NASH. The multivariate
      analysis identified four independent predictive factors for the presence of NASH:
      CRP (p=0.004), SLD (p=0.018), HOMA (p=0.03) and albumin level (p=0.041). The
      variables independently associated with severe fibrosis were albumin (p=0.008),
      blood glucose (p=0.017) and BMI (p=0.048). CONCLUSION: A predictive model that
      incorporates the clinical and biological parameters may identify at-risk patients
      with NAFLD, avoiding liver biopsy on a routine basis.

PMID- 21725513
TI  - Renal function after dopamine and fluid administration in patients with malignant
      obstructive jaundice. A prospective randomized study.
AB  - BACKGROUND AND AIMS: Acute renal failure is a relevant complication in
      obstructive jaundice (OJ). The extracellular water volume (ECW) depletion and
      myocardial dysfunction affects haemodynamic and renal disturbance in patients
      with OJ. METHODS: A prospective open randomised study was conducted to evaluate
      the effect of peridrainage saline infusion associated with dopamine
      administration on hormonal and renal function derangements in 102 patients with
      malignant OJ. Patients were randomly distributed according to whether (n=64) or
      not (n=38) received dopamine with saline solution before endoscopic biliary
      drainage. Furthermore, patients receiving dopamine were randomly distributed
      whether (n=31) or not (n=33) received additional dopamine administration during
      the postdrainage phase. Different parameters such as ECW, serum levels of
      aldosterone, renin, atrial natriuretic peptide (ANP), antidiuretic hormone (ADH),
      endothelin-1 (ET-1), urine PGE2 and creatinine clearance (CrCl) were analyzed.
      RESULTS: Fluid administration was accompanied by an increase in the ECW (p=0.01)
      and an improvement in the CrCl (p=0.01). Dopamine increased CrCl by 11% (p=0.04)
      and reduced urinary PGE2 concentration (p=0.02). After drainage, a transient
      worsening of CrCl was seen in patients on i.v. fluid infusion alone but not in
      dopamine groups (p=0.001). Improvement of CrCl after dopamine administration was
      found in patients with serum bilirubin > 16 mg/dl and sodium urine excretion <145
      mEq/l. CONCLUSIONS: The administration of dopamine associated with appropriate
      i.v. fluid infusion in the peridrainage period has an impact on renal function
      only in selected patients with malignant biliary obstruction. This effect is more
      relevant in patients with higher marked cholestasis.

PMID- 21725514
TI  - Partial pressure of NH3 in cirrhotic patients with and without hepatic
      encephalopathy.
AB  - BACKGROUND AND AIMS: Although the exact pathogenetic factor in hepatic
      encephalopathy is still unknown, ammonia is considered to be the major cause of
      neurotoxicity. However, previous studies on the relationship between ammonia and
      the severity of hepatic encephalopathy have yielded variable results. Since
      unionized ammonia is the only form of ammonia that is able to freely spread
      through the blood-brain barrier and cause cerebral dysfunction, we tested the
      hypothesis that concentration of unionized ammonia is correlated with the
      severity of hepatic encephalopathy. METHODS: 156 patients with cirrhosis (74 with
      hepatic encephalopathy and 82 without) were enrolled, and underwent clinical
      examination and blood testing. Ammonia, pNH3 and pH determinations were repeated
      after two days of treatment. The differences in venous ammonia, pNH3, and pH
      among patients with and without encephalopathy were analyzed. RESULTS: Among
      cirrhotic patients with hepatic encephalopathy, pH, pNH3 and ammonia levels were
      all higher than those among patients without hepatic encephalopathy, and
      alkalosis was more common in patients with hepatic encephalopathy. Both venous
      ammonia and pNH3 were significantly correlated to the clinical grade of hepatic
      encephalopathy; however, the r was similar for venous ammonia (r=0.63) and pNH3
      (r=0.68). The follow-up of 20 patients showed that the median levels of pH, pNH3
      and venous ammonia decreased; venous ammonia levels were unchanged or higher in
      some patients after resolution of hepatic encephalopathy. CONCLUSION: This study
      supports that pH-dependant pNH3 and pH could be useful diagnostic and prognostic
      tools in cirrhotic patients with hepatic encephalopathy.

PMID- 21725515
TI  - Pancreatic cyst fluid analysis--a review.
AB  - An increased number of pancreatic cysts are being diagnosed due to the increased
      usage of cross-sectional imaging. Endoscopic ultrasound (EUS)-guided fine needle
      aspiration (FNA) cytology and molecular analysis of these cystic lesions have led
      to their better detection and characterization. The aim of this review is to
      assess the value of cyst fluid analysis for the differential diagnosis of
      pancreatic cystic lesions, in view of the recent progresses of molecular analysis
      methods. Pancreatic cysts can be either simple (retention) cysts, pseudocysts and
      cystic neoplasms, while these are further subdivided into serous cystadenomas,
      mucinous cystic neoplasms (MCNs) or intraductal papillary mucinous neoplasms
      (IPMNs). EUS is now being used to investigate cystic pancreatic lesions,
      particularly by means of EUS guided cyst aspiration and sampling of the cyst wall
      or septa, as well as mural nodules. Cyst fluid can be further studied after
      aspiration in order to analyze cytology, viscosity, extracellular mucin, other
      tumor markers (CEA, CA 19-9,CA 15-3, Ca 72-4, etc.), enzymes (amylase, lipase),
      as well as DNA analysis of DNA quality/content or mutational analysis to study
      allelic imbalance/LOH (loss of heterozygosity) and K-ras mutations. After careful
      review of the published studies, a conclusion was reached that the use of tumor
      and molecular markers in conjunction with multimodality detection methods such as
      CT, MR and EUS-FNA allows risk stratification, while being also cost-effective.

PMID- 21725516
TI  - CT and MR imaging of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common tumor in the world and
      the incidence is expected to increase in the future due to hepatitis viral
      infections and increasing cirrhosis incidence. The diagnosis of HCC is no longer
      based on biopsy especially in cases when curative treatment is possible. The
      imaging criteria are usually based on the vascular findings of HCC (e.g. early
      arterial uptake followed by washout in the portovenous and equilibrium phase).
      However, there are several limitations of the assessment of HCC by using only the
      vascular criteria. The use of tissue-specific contrast agents, including
      superparamagnetic iron oxides and hepatobiliary contrast agents, improves lesion
      detection and characterization. Therefore, an accurate diagnosis of HCC implies,
      at this moment, a combination of vascular and cellular information. This review
      focuses on the most important findings provided by the unenhanced and dynamic
      enhanced CT and MR images regarding HCC evaluation. We also discuss the various
      imaging characteristics of HCC at MR imaging after the administration of tissue
      specific contrast agents.

PMID- 21725517
TI  - Usefulness of contrast enhanced ultrasound guidance in percutaneous biopsies of
      liver tumors.
AB  - The performance of percutaneous echoguided biopsy in hepatic tumor diagnosis is
      limited by several factors, among which tumor characteristics such as tumor type,
      size and location play an important role. With all the advantages offered by
      ultrasound guidance, the overall sensitivity of this method in the tumor
      diagnosis has remained around 90%. Contrast enhanced ultrasound (CEUS) guided
      percutaneous biopsy is a new developed technique aimed at increasing the accuracy
      of percutaneous biopsies. With new ultrasound devices comprising the split-screen
      mode, which displays both the CEUS and background B-mode US image simultaneously
      on a single monitor, the procedure is now technically feasible. CEUS guided
      percutaneous liver biopsy should be applied in large tumors with consistent
      necrosis, in hypovascular tumors or in those invisible or poorly visible to
      conventional ultrasound. An increased accuracy was demonstrated in poorly visible
      or invisible hepatic lesions and when CEUS was used before biopsy.

PMID- 21725518
TI  - Carcinosarcoma of the pancreas: a unique case with emphasis on metaplastic
      transformation and the presence of undifferentiated pleomorphic high-grade
      sarcoma.
AB  - We report a rare case of pancreatic carcinosarcoma in a 48-year-old man. An
      abdominal ultrasound scan incidentally detected a large heterogeneous mass in the
      left upper quadrant. CT and MRI scans indicated a rapidly growing unilocular
      cystic mass in the pancreatic tail. Grossly, the resected pancreatic mass
      measured 7*5*5 cm and consisted of a unilocular cystic lesion that had several
      solid mural nodules. Microscopically, the cystic wall showed two carcinomatous
      components, mucinous cystadenocarcinoma and anaplastic carcinoma. The solid
      lesion predominantly consisted of pleomorphic spindle cells arranged in
      interlacing fascicles which had infiltrated the adjacent pancreatic parenchyma.
      In some areas of this sarcomatous component, anaplastic carcinoma cells
      intermingled with or transformed into spindle cells. Immunohistochemically, the
      carcinomatous components were strongly positive for epithelial markers, and
      transforming anaplastic carcinoma cells were immunoreactive for both epithelial
      markers and vimentin; in contrast, the sarcomatous component was strongly
      positive for only vimentin. Additionally, an identical mutation (G to A
      transition) at codon 12 of K-ras gene and concordant immunoreactivity for p53
      protein were detected in the carcinomatous and sarcomatous components. These
      findings suggested that the pancreatic carcinosarcoma could be of monoclonal
      origin, and that the sarcomatous component might have arisen from metaplastic
      transformation of the carcinomatous component.

PMID- 21725519
TI  - Adalimumab-induced lupus erythematosus with central nervous system involvement in
      a patient with Crohn's disease.
AB  - The anti-tumor necrosis factor (TNF) agents are drugs that in recent years turned
      out to be a mainstay of therapy for the treatment of inflammatory bowel disease.
      Nevertheless, they have several adverse effects such as infectious complications
      and immunogenicity. One of the most common immunogenic effects is the development
      of autoantibodies, mainly anti-nuclear antibodies and anti-double-stranded DNA
      antibodies, only rarely associated with overt clinical manifestations of systemic
      lupus erythematosus. Adalimumab is a fully humanized monoclonal antibody widely
      used for the treatment of Crohn's disease and supposed to have less immunogenic
      activity and a safer profile than other anti-TNF agents. The occurrence of
      systemic lupus erythematosus with involvement of the central nervous system
      appears to be a very rare complication of such drugs, and no cases have been
      reported in the medical literature in patients treated with adalimumab. We report
      a case of a 53 years-old woman with ileo-colic Crohn's disease where the
      treatment with adalimumab was complicated by systemic lupus erythematosus with
      central nervous system vasculitis.

PMID- 21725520
TI  - Ampullary cancer with pancreas divisum treated by endoscopic partial
      papillectomy: a case report.
AB  - We herein report a case of ampullary cancer associated with pancreas divisum.
      Duodenoscopy revealed a tumor at the ampulla of Vater with a normal ampullary
      orifice. Intraductal ultrasonography showed a hypoechoic mass limited to the
      ampulla of Vater. ERCP showed an arborizing ventral pancreatic duct without
      connection to the dorsal duct. Endoscopic snare resection of the tumor was
      performed following biliary stenting. Histological examination revealed well
      differentiated tubular adenocarcinoma limited to the ampulla of Vater. Endoscopic
      papillectomy with the assistance of a biliary stent is useful in cases of
      ampullary neoplasm with a normal ampullary orifice in order to avoid ductal
      injury.

PMID- 21725521
TI  - Extrahepatic biliary cystadenoma with mesenchymal stroma: a true biliary
      cystadenoma? A case report.
AB  - Biliary cystadenomas are benign but potentially malignant cystic neoplasms, which
      classically contain mesenchymal stroma similar to ovarian tissue. We report a
      case of an extra-hepatic biliary cystadenoma with mesenchymal stroma along with a
      discussion of current pathological opinion. CASE PRESENTATION: A 54-year-old
      female presented with abdominal pain, abnormal liver function tests and a mass on
      ultrasound. Computerized Tomography identified a complex multi-locular cyst in
      the common hepatic duct. Radical excision of the lesion and a Roux-en-Y loop
      bilio-enteric anastomosis was performed. Histology confirmed the presence of a
      benign biliary cystadenoma with ovarian type stroma. CONCLUSION: Biliary
      cystadenomas classically contain mesenchymal stroma similar to ovarian tissue. It
      now appears that cystadenomas without mesenchymal stroma appear to be more akin
      to similar cystic lesions of the pancreas, and may represent a dissimilar
      neoplasm. Therefore, malignant transformation can occur, so complete excision is
      recommended.

PMID- 21725522
TI  - Living donor liver transplantation as treatment for diffuse Caroli's disease.

PMID- 21725523
TI  - Ecstasy induced fatal hepatic failure.

PMID- 21725524
TI  - EUS-FNA using a forward-view echoendoscope in difficult cases.

PMID- 21725525
TI  - "Clicking" on/with polymers: a rapidly expanding field for the straightforward
      preparation of novel macromolecular architectures.
AB  - The combination of controlled polymerization techniques and "click" reactions
      form an efficient platform for the preparation of polymers in various
      architectures. In this critical review, an update of our 2007 review in Chem.
      Soc. Rev., we focus on the "click" reactions that have been used widely in the
      last four years to create new polymer architectures. Not only block copolymers
      and star-shaped polymers but also cyclic and dendritic macromolecules could be
      synthesized using these robust "click" reactions (205 references).

PMID- 21725526
TI  - Intermolecular hydroamination of oxygen-substituted allenes. New routes for the
      synthesis of N,O-chelated zirconium and titanium amido complexes.
AB  - Intermolecular hydroamination of heteroatom-substituted allenes with a bulky
      arylamine was carried out using a bis(amidate) bis(amido) titanium(IV) complex
      (1) as a precatalyst. The reaction of 2,6-dimethylaniline with oxygen-substituted
      allene 2c or 2d in the presence of complex 1 gives the ketimine regioisomer as
      the exclusive product. Reduction of such ketimine products resulted in the
      formation of amino ethers that were further employed as proligands for the
      formation of N,O-chelating five-membered titana- and zirconacycles. Such
      sterically demanding N,O-chelating ligands result in the high-yielding
      preparation of mono-ligated products. Solid-state molecular structures of all the
      complexes revealed distorted trigonal bipyramidal geometry about the metal
      centers, with a dative bond between the metal and the oxygen donor atom. These
      new complexes obtained using hydroamination as the key-step in ligand preparation
      were also shown to be useful cyclohydroamination precatalysts in their own right.

PMID- 21725527
TI  - An unprecedented strategy for selective and sensitive fluorescence detection of
      nitric oxide based on its reaction with a selenide.
AB  - A new strategy that utilizes the interaction between NO and a selenide is
      reported for fluorescence detection of NO, in which rhodamine B selenolactone
      serves as a model selenide.

PMID- 21725528
TI  - A three-way synergy of triple-modified Bi2WO6/Ag/N-TiO2 nanojunction film for
      enhanced photogenerated charges utilization.
AB  - We demonstrate a general strategy to prepare Bi(2)WO(6)/Ag/N-TiO(2) film with
      double visible-light-active components bridged by Ag nanoparticles as an electron
      shuttle, which exhibits enhanced photocatalytic activity and photoelectrochemical
      performance under visible light.

PMID- 21725529
TI  - Synthetic strategies for the surface functionalisation of gold nanoparticles with
      metals and metal clusters.
AB  - The reaction of the new ditopic thiol-phosphine compound
      HS(CH(2))(11)OOCC(6)H(4)PPh(2) (L) with an excess of dodecanethiol-protected gold
      nanoparticles gave the asymmetric gold complex
      [CH(3)(CH(2))(11)SAuPPh(2)C(6)H(4)COO(CH(2))(11)SH] (4), but no phosphine
      protected gold nanoparticles were formed. However, by blocking the phosphine
      function in L with metal fragments, we have been able to produce gold
      nanoparticles functionalised with AuCl- and cluster [Fe(2)(CO)(7)Au] units on the
      surface by the method of ligand-place exchange reaction.

PMID- 21725530
TI  - Recent advances in hierarchically structured zeolites: synthesis and material
      performances.
AB  - Hierarchically structured zeolites (HSZs) have attracted increasing attention in
      the last few years, thanks to their unique hierarchical porous structures
      combining micro- and mesoporosity and superior material performances, especially
      in the bulky molecules-involved catalysis and adsorption applications. In this
      Feature Article, the recent advances in the HSZs synthetic methodologies and
      material performances in catalysis are overviewed. Further, some perspectives for
      the future development of HSZs are discussed.

PMID- 21725531
TI  - Fibrous nanocomposites of carbon nanotubes and graphene-oxide with synergetic
      mechanical and actuative performance.
AB  - Fibrous nanocomposites of carbon nanotubes, graphene-oxide or graphene were
      prepared by a simple coagulation spinning technique exhibiting synergetic
      enhancement of mechanical strength, electronic conductivity and electrical
      actuation performance.

PMID- 21725532
TI  - Self-assembling nanomicelles of a novel camptothecin prodrug engineered with a
      redox-responsive release mechanism.
AB  - A novel amphiphilic camptothecin prodrug that spontaneously arranges into
      nanomicelles which preferentially release the cytotoxic drug under tumor-relevant
      reductive conditions is designed.

PMID- 21725533
TI  - Bottom-up fabrication of redox-active metal complex oligomer wires on an H
      terminated Si(111) surface.
AB  - Linear and branched Fe(tpy)(2) complex oligomer wires were quantitatively formed
      on hydrogen-terminated silicon wafers by means of hydrosilylation of
      ethynylterpyridine and following stepwise coordination reactions, and the redox
      property of surface-attached species and its photosensitivity can be controlled
      by the doping density of the silicon wafers.

PMID- 21725534
TI  - Facile one-pot preparation of thermally and photochemically convertible soluble
      precursors of copper phthalocyanine and naphthalocyanine.
AB  - Soluble copper phthalocyanine (CuPc) and naphthalocyanine (CuNc) precursors which
      can be converted thermally and photochemically into insoluble CuPc and CuNc,
      respectively, have been synthesized by a one-step reaction using commercially
      available chemicals.

PMID- 21725535
TI  - Effects of flow-selectivity on self-assembly and auto-organization processes: an
      example.
AB  - The homoassociation of H(4)TPPF(5)S(3) leads to different J-aggregates depending
      on whether solutions are shaken (homogenization) or stirred magnetically (square
      section flask). Vortex stirring due to the generation of laminar flows decreases
      lateral diffusion therefore it inhibits cluster-to-cluster aggregation
      mechanisms.

PMID- 21725541
TI  - Metal-free oxygenation of cyclohexane with oxygen catalyzed by 9-mesityl-10
      methylacridinium and hydrogen chloride under visible light irradiation.
AB  - Photooxygenation of cyclohexane by O(2) occurs efficiently under visible-light
      irradiation of an O(2)-saturated acetonitrile solution containing 9-mesityl-10
      methylacridinium ions (Acr(+)-Mes) and HCl to yield cyclohexanone, cyclohexanol
      and hydrogen peroxide. The photocatalytic reaction is initiated by electron
      transfer from Cl(-) to the mesitylene radical cation moiety.

PMID- 21725542
TI  - Efficient chemoenzymatic synthesis of sialyl Tn-antigens and derivatives.
AB  - An N-terminal and C-terminal truncated recombinant alpha2-6-sialyltransferase
      cloned from Photobacterium sp. JH-ISH-224, Psp2,6ST(15-501)-His(6), was shown to
      be an efficient catalyst for one-pot three-enzyme synthesis of sialyl Tn (STn)
      antigens and derivatives containing natural and non-natural sialic acid forms.

PMID- 21725543
TI  - Design and characterization of an electrochemical peptide-based sensor fabricated
      via"click" chemistry.
AB  - We report an electrochemical peptide-based sensor fabricated via'click' chemistry
      for detection of anti-p24 antibodies. Our results also allude to a signaling
      mechanism similar to that of the linear probe electrochemical DNA sensor.

PMID- 21725544
TI  - Iron sulfide-embedded carbon microsphere anode material with high-rate
      performance for lithium-ion batteries.
AB  - Iron sulfide-embedded carbon microspheres were prepared via a solvothermal
      process and show high specific capacity and excellent high-rate performance as
      anode material for lithium-ion batteries.

PMID- 21725545
TI  - Reassembly self-sorting triggered by heterodimerization.
AB  - We report herein a five-component self-sorted system comprising molecular clips
      that form heterodimers 1.4 and 8.11, and homodimer 14.14 in
      C(6)D(5)CD(3)/CDCl(3). The three component self-sorting mixture comprising 1.1,
      8.8, and 14.14 undergoes triggered reassembly self-sorting upon addition of 4.4
      and 11.11.

PMID- 21725546
TI  - The dynamic nature of amyloid beta (1-40) aggregation.
AB  - In this paper, we characterize the dynamic nature of the full amyloid beta (1-40)
      (Abeta (1-40)) aggregates. We labeled the peptide with either 5
      carboxytetramethylrhodamine (TAMRA) or with fluorescein-isothiocyanate (FITC).
      The labeled peptides were mixed after separate fibrillization, and the dynamic
      changes in the structure of the fibrils were imaged using confocal microscopy.
      Fluorescence resonance energy transfer (FRET) measurements showed that the Abeta
      (1-40) peptides detach from and reattach to the fibrils in a biologically
      relevant timescale (days). With time, the two peptides mix at the molecular
      level. This process is concentration dependent and occurs primarily in the
      external parts of the aggregates with a half time between 4 and 7 days. This
      study shows that the combination of confocal microscopy and FRET analysis is a
      facile method for studying dynamic processes in supra-molecular aggregates.

PMID- 21725547
TI  - Theoretical investigations of the reactivities of saturated five-membered ring N
      heterocyclic carbenes with heavier group 14 elements.
AB  - The potential energy surfaces for the chemical reactions of group 14 carbenes
      have been studied using density functional theory (B3LYP/LANL2DZ). Five saturated
      five-membered-ring N-heterocyclic carbene Dipp[upper bond 1
      start]N(CH(2))(2)N(Dipp)E[upper bond 1 end]: (five-ring-E:) species, where E = C,
      Si, Ge, Sn and Pb, have been chosen as model reactants in this work. Also, four
      kinds of chemical reactions; addition of water, methane insertion, alkene
      cycloaddition and dimerization, have been used to study the chemical reactivities
      of these group 14 carbenes. The present theoretical investigations suggest that
      the relative carbenic reactivity decreases in the order: C > Si > Ge > Sn > Pb.
      That is, the heavier the group 14 atom (E), the more stable is the carbene
      towards chemical reactions. This may be the reason that there have been many
      instances reported of the synthesis and characterization of stable group 14 five
      membered-ring N-heterocyclic carbene species with various alkyl protecting
      substituents at room temperature. Furthermore, the singlet-triplet energy
      splitting of the five-ring-E:, as described in the configuration mixing model
      attributed to the work of Pross and Shaik, can be used as a diagnostic tool to
      predict their reactivities. The results obtained allow a number of predictions to
      be made.

PMID- 21725548
TI  - Effect of ligand substituents in olefin polymerisation by half-sandwich titanium
      complexes containing monoanionic iminoimidazolidide ligands-MAO catalyst systems.
AB  - Various half-sandwich titanium complexes containing iminoimidazolidide ligands,
      CpTiCl(2)[1,3-R(2)(CH(2)N)(2)C=N] (1a-d) [R = Ph (a), 2,6-Me(2)C(6)H(3) (b),
      cyclohexyl (c), (t)Bu (d)], have been employed as the catalyst precursors for
      ethylene polymerisation, syndiospecific styrene polymerisation, and
      copolymerisation of ethylene with 1-hexene in the presence of MAO cocatalyst; 1d
      showed the highest catalytic activity for ethylene polymerisation whereas 1b
      showed the highest activity for syndiospecific styrene polymerisation.

PMID- 21725549
TI  - Determination of polycyclic aromatic hydrocarbons with molecular weight 302 in
      water samples by solid-phase nano-extraction and laser excited time-resolved
      Shpol'skii spectroscopy.
AB  - Monitoring of high-molecular weight polycyclic aromatic hydrocarbons (HMW-PAH)
      via simple and cost effective methods still remains a challenge. In this article,
      we combine solid-phase nano-extraction (SPNE) and 4.2 K laser-excited time
      resolved Shpol'skii spectroscopy (LETRSS) into a valuable alternative for the
      water analysis of dibenzo[a,l]pyrene, dibenzo[a,h]pyrene, dibenzo[a,i]pyrene and
      naphtho[2,3-a]pyrene. In comparison to the original SPNE procedure, the present
      method improves PAH recoveries and reduces extraction time from 30 to 20 min per
      sample. Quantitative release of HMW-PAH into the Shpol'skii matrix (n-octane) is
      best accomplished with a mixture of 48 MUL of methanol and 2 MUL of 1
      pentanethiol. Their migration into the 50 MUL layer of n-octane provides highly
      resolved spectra with distinct fluorescence lifetimes for unambiguous isomer
      determination. Complete analysis takes less than 30 min per sample and consumes
      only 100 micro-liters of organic solvents. 500 MUL of water are sufficient to
      obtain limits of detection ranging from 16 ng L(-1) (dibenzo[a,l]pyrene) to 55 ng
      L(-1) (dibenzo[a,i]pyrene), relative standard deviations better than 3% and
      analytical recoveries above 90%. Although a straightforward comparison to
      chromatographic methods is not possible because of the lack of analytical figures
      of merit on HMW-PAH, the excellent precision of measurements, limits of detection
      and overall recoveries makes SPNE-LETRSS an attractive approach to water analysis
      of HMW-PAH.

PMID- 21725550
TI  - Novel heterobimetallic ruthenium(III)-cobalt(II) compounds constructed from trans
      [Ru(III)(Q)2(CN)2](-) (Q = 8-quinolinolato): synthesis, structures and magnetic
      properties.
AB  - Reaction of [Ru(II)(PPh(3))(3)Cl(2)] with HQ and KCN produces a new
      dicyanoruthenium(III) building block, [Ru(III)(Q)(2)(CN)(2)](-). It reacts with
      hydrated CoCl(2) in MeOH or DMF to produce a trinuclear compound 2 or a 1-D
      zigzag chain 3.

PMID- 21725551
TI  - Gold-catalysed alkenyl- and arylsilylation reactions forming 1-silaindenes.
AB  - In the presence of gold(I)-phosphine catalysts, alkenyl- and arylsilanes undergo
      intramolecular cyclisation reactions onto appendant alkyne moieties to afford 1
      silaindene derivatives. The reaction pathways vary depending on the substituent
      on silicon.

PMID- 21725552
TI  - Ultrafast REMPI in benzene and the monohalobenzenes without the focal volume
      effect.
AB  - We report on the photoionization and photofragmentation of benzene (C(6)H(6)) and
      of the monohalobenzenes C(6)H(5)-X (X = F, Cl, Br, I) under intense-field, single
      molecule conditions. We focus 50-fs, 804-nm pulses from a Ti:sapphire laser
      source, and record ion mass spectra as a function of intensity in the range
      ~10(13) W/cm(2) to ~10(15) W/cm(2). We count ions that were created in the
      central, most intense part of the focal area; ions from other regions are
      rejected. For all targets, stable parent ions (C(6)H(5)X(+)) are observed. Our
      data is consistent with resonance-enhanced multiphoton ionization (REMPI)
      involving the neutral (1)pipi* excited state (primarily a phenyl excitation): all
      of our plots of parent ion yield versus intensity display a kink when this
      excitation saturates. From the intensity dependence of the ion yield we infer
      that both the HOMO and the HOMO-1 contribute to ionization in C(6)H(5)F and
      C(6)H(5)Cl. The proportion of phenyl (C(6)H(5)) fragments in the mass spectra
      increases in the order X = F, Cl, Br, I. We ascribe these substituent-dependent
      observations to the different lifetimes of the C(6)H(5)X (1)pipi* states. In X =
      I the heavy-atom effect leads to ultrafast intersystem crossing to a dissociative
      (3)nsigma* state. This breaks the C-I bond in an early stage of the ultrashort
      pulse, which explains the abundance of fragments that we find in the iodobenzene
      mass spectrum. For the lighter X = F, Cl, and Br this dissociation is much
      slower, which explains the lesser degree of fragmentation observed for these
      three molecules.

PMID- 21725553
TI  - Faster oxygen atom transfer catalysis with a tungsten dioxo complex than with its
      molybdenum analog.
AB  - The synthesis and characterization of a series of molybdenum ([MoO(2)Cl(L(n))];
      L(1) (1), L(2) (3)) and tungsten ([WO(2)Cl(L(n))]; L(1) (2), L(2) (4)) dioxo
      complexes (L(1) = 1-methyl-4-(2-hydroxybenzyl)-1,4-diazepane and L(2) = 1-methyl
      4-(2-hydroxy-3,5-di-tert-butylbenzyl)-1,4-diazepane) of tridentate
      aminomonophenolate ligands HL(1) and HL(2) are reported. The ligands were
      obtained by reductive amination of 1-methyl-1,4-diazepane with the corresponding
      aldehyde. Complexes 3 and 4 were obtained by the reaction of [MO(2)Cl(2)(dme)(n)]
      (M = Mo, n = 0; W, n = 1) with the corresponding ligand in presence of a base,
      whereas for the preparation of 1 and 2 the ligands were deprotonated by KH prior
      to the addition to the metal. They were characterized by NMR and IR spectroscopy,
      by cyclic voltammetry, mass spectrometry, elemental analysis and by single
      crystal X-ray diffraction analysis. Solid-state structures of the molybdenum and
      tungsten cis-dioxo complexes reveal hexa-coordinate metal centers surrounded by
      two oxo groups, a chloride ligand and by the tridentate monophenolate ligand
      which coordinates meridionally through its [ONN] donor set. In the series of
      compounds 1-4, complexes 3 and 4 have been used as catalysts for the oxygen atom
      transfer reaction between dimethyl sulfoxide (DMSO) and trimethyl phosphine
      (PMe(3)). Surprisingly, faster oxygen atom transfer (OAT) reactivity has been
      observed for the tungsten complex [WO(2)Cl(L(2))] (4) in comparison to its
      molybdenum analog [MoO(2)Cl(L(2))] (3) at room temperature. The kinetic results
      are discussed and compared in terms of their reactivity.

PMID- 21725554
TI  - Ferromagnetic and antiferromagnetic copper(II) complexes: counterplay between
      zero-field effects of the quartet ground state and intermolecular interactions.
AB  - The linear trinuclear Cu(II) complexes [Cu(3)(L(1))(4)(H(2)tea)(2)] (1),
      [Cu(3)(L(2))(4)(H(2)tea)(2)].2CH(3)CN (2), [Cu(3)(L(2))(4)(H(2)tea)(2)] (3),
      [Cu(3)(L(1))(2)(H(2)tea)(2)(NO(3))(2)] (4) and the dinuclear complex
      [Cu(2)(L(1))(2)(H(2)tea)(2)] (5), where L(1) = 2-thiophene carboxylate, L(2) = 2
      (thiophen-2-yl)-acetate and H(2)tea = the single deprotonated form of
      triethanolamine have been prepared and characterised while the crystal structures
      of 1-4 have been determined. The variable-temperature magnetic susceptibilities
      of complexes 1-5 have been measured in the range 2-300 K under various external
      fields in the range 0.02-1.0 T. X-band EPR spectra of 1-5 compounds were recorded
      at 4-100 K. Complexes 1, 2 and 3 found to have the same J = 33 cm(-1) and g
      values 2.16(1), 2.20(1) and 2.16(1) respectively while for 5 J = 15 cm(-1) and g
      = 2.06(1) revealing a clear ferromagnetic exchange between Cu(II) ions. Complex 4
      was found to be antiferromagnetic with J = -28 cm(-1) and g = 2.21(1). The
      polycrystalline powder X-band EPR spectrum of complexes 1, 2, and 3 at 4 K are
      dominated by a transition at 1600 G (g = 4.3) which unambiguously identifies the
      spin of the ground multiplet (S = 3/2) while the antiferromagnetic complex 4 has
      a derivative centered at g = 2.1 indicative of a ground doublet (S = 1/2).
      Concerning complex 5 a spectrum of a dominant derivative centered at g = 2.06(1)
      is observed with a very weak half field transition (ca. 1500 G) indicative of the
      ferromagnetic nature of the system. Furthermore, for complexes 2 and 3 a strong
      temperature dependence of this spectroscopic g-factor is revealed and change of
      the g(eff) from the liquid helium temperature to the room temperature is almost 2
      units.

PMID- 21725555
TI  - Extremely bulky amido-group 14 element chloride complexes: potential synthons for
      low oxidation state main group chemistry.
AB  - The preparation of a series of extremely bulky secondary amines, Ar*N(H)SiR(3)
      (Ar* = C(6)H(2){C(H)Ph(2)}(2)Me-2,6,4; R(3) = Me(3), MePh(2) or Ph(3)) is
      described. Their deprotonation with either LiBu(n), NaH or KH yields alkali metal
      amide complexes, several monomeric examples of which, [Li(L){N(SiMe(3))(Ar*)}] (L
      = OEt(2) or THF), [Na(THF)(3){N(SiMe(3))(Ar*)}] and [K(OEt(2)){N(SiPh(3))(Ar*)],
      have been crystallographically characterised. Reactions of the lithium amides
      with germanium, tin or lead dichloride have yielded the first structurally
      characterised two-coordinate, monomeric amido germanium(II) and tin(II) chloride
      complexes, [{(SiR(3))(Ar*)N}ECl] (E = Ge or Sn; R = Me or Ph), and a chloride
      bridged amido-lead(II) dimer, [{[(SiMe(3))(Ar*)N]Pb(MU-Cl)}(2)]. DFT calculations
      on [{(SiMe(3))(Ar*)N}GeCl] show its HOMO to exhibit Ge lone pair character and
      its LUMO to encompass its Ge based p-orbital. A series of bulky amido silicon(IV)
      chloride complexes have also been prepared and several examples,
      [{(SiR(3))(Ar*)N}SiCl(3)] (R(3) = Me(3), MePh(2)) and
      [{(SiMe(3))(Ar*)N}SiHCl(2)], were crystallographically characterised. The
      sterically hindered group 14 complexes reported in this study hold significant
      potential as precursors for kinetically stabilised low oxidation state and/or low
      coordination number group 14 complexes.

PMID- 21725556
TI  - Exploratory studies on coordination chemistry of a redox-active bridging ligand:
      synthesis, properties and solid state structures of the complexes.
AB  - The explorative coordination chemistry of the bridging ligand TTF-PPB is
      presented. Its strong binding ability to Co(II) and then to Ni(II) or Cu(II) in
      the presence of hexafluoroacetylacetonate (hfac(-)), forming new mono- and
      dinuclear complexes 1-3, is described. X-ray crystallographic studies have been
      conducted in the case of the free ligand TTF-PPB as well as its complexes [Co(TTF
      PPB)(hfac)(2)] (1) and [Co(hfac)(2)(MU-TTF-PPB)Ni(hfac)(2)] (2). Each metal ion
      is bonded to two bidentate hfac(-) anions through their oxygen atoms and two
      nitrogen atoms of the PPB moiety with a distorted octahedral coordination
      geometry. Specifically, nitrogen donor atoms of TTF-PPB adopt a cis-coordination
      but not in the equatorial plane, which is quite rare. Electronic absorption,
      photoinduced intraligand charge transfer ((1)ILCT), and electrochemical behaviour
      of 1-3 have been investigated. UV-Vis spectroscopy shows very strong bands in the
      UV region consistent with ligand centred pi-pi* transitions and an intense broad
      band in the visible region corresponding to a spin-allowed pi-pi* (1)ILCT
      transition. Upon coordination, the (1)ILCT band is bathochromically shifted by
      3100, 6100 and 5900 cm(-1) on going from 1 to 3. The electrochemical studies
      reveal that all of them undergo two reversible oxidation and one reversible
      reduction processes, ascribed to the successive oxidations of the TTF moiety and
      the reduction of the PPB unit, respectively.

PMID- 21725557
TI  - Integrated immunoassay using tuneable surface acoustic waves and lensfree
      detection.
AB  - The diagnosis of infectious diseases in the Developing World is technologically
      challenging requiring complex biological assays with a high analytical
      performance, at minimal cost. By using an opto-acoustic immunoassay technology,
      integrating components commonly used in mobile phone technologies, including
      surface acoustic wave (SAW) transducers to provide pressure driven flow and a
      CMOS camera to enable lensfree detection technique, we demonstrate the potential
      to produce such an assay. To achieve this, antibody functionalised microparticles
      were manipulated on a low-cost disposable cartridge using the surface acoustic
      waves and were then detected optically. Our results show that the biomarker,
      interferon-gamma, used for the diagnosis of diseases such as latent tuberculosis,
      can be detected at pM concentrations, within a few minutes (giving high
      sensitivity at a minimal cost).

PMID- 21725558
TI  - Quantum stereodynamics of Li + HF reactive collisions: the role of reactants
      polarization on the differential cross section.
AB  - A complete quantum study for the state-to-state Li + HF(v,j,m) ->
      LiF(v',j',Omega') + H reactive collisions has been performed using a wave packet
      method, for different initial rotational states and helicity states of the
      reactants. The state-to-state differential cross section has been simulated, and
      the polarization of products extracted. It is found that the reactivity is
      enhanced for nearly collinear collisions, which produces a vibrational excitation
      of HF, needed to overcome the late barrier. It is also found that LiF(v' = 0)
      products are preferentially forward scattered, while vibrationally excited LiF(v'
      = 1 and 2) are backward scattered. These results are interpreted with a simple
      reaction mechanism, based on the late character and bent geometry of the
      transition state, originating from a covalent/ionic crossing, which consists of
      two steps: the arrival at the transition state and the dissociation. In the first
      step, in order to get to the saddle point some HF vibrational excitation is
      required, which favors head-on collisions and therefore low values of m. In the
      second step a fast dissociation of H atom takes place, which is explained by the
      ionic Li(+)F(-)H character of the bent transition state: the FH(-) is repulsive
      making that H depart rapidly leaving a highly rotating LiF molecule. For the
      higher energy analyzed, where resonances slightly contribute, the orientation and
      alignment of product rotational states, referred to as reactants frame (with the
      z-axis parallel to k), are approximately constant with the scattering angle. The
      alignment is close to -1, showing that j' is perpendicular to k, while starting
      from initial states with well defined rotational orientation, as states with pure
      m values, the final rotational are also oriented. It is also found that when
      using products frame (with the z'-axis parallel to k') the rotational alignment
      and orientation of products varies a lot with the scattering angle just because
      the z' axis changes from being parallel to anti-parallel to k when varying from
      theta = 0 to pi.

PMID- 21725559
TI  - Aromaticity in heterocyclic analogues of benzene: comprehensive analysis of
      structural aspects, electron delocalization and magnetic characteristics.
AB  - The degree of aromaticity of six-membered monoheterocycles with IV-VI group
      heteroatoms (C(6)H(5)X, where X = SiH, GeH, N, P, As, O(+), S(+), Se(+)) was
      analyzed using the results of ab initio calculations at the MP2/cc-pvtz level.
      Values of common aromaticity indices including those based on electronic
      delocalization properties, structural-dynamic features and magnetic properties
      all indicate high aromaticity of all considered heterocycles. A decrease in
      aromaticity is observed with increasing atomic number of the heteroatom, except
      in the case of the pyrylium cation. However, not all types of indices or even
      different indices within the same type correlate well among each other. Ring
      currents have been obtained at the HF/cc-pvdz level using the ipsocentric
      formulation. Ring current maps indicate that in the case of cationic heterocycles
      the ring current persists in all molecules under consideration. The different
      conclusions reached depending on the type of index used are a manifestation of
      the fact that when not dealing with hydrocarbons, aromaticity is ill-defined. One
      should always express explicitly which property of the molecules is considered to
      establish a degree of "aromaticity".

PMID- 21725560
TI  - Holo-Ni2+ Helicobacter pylori NikR contains four square-planar nickel-binding
      sites at physiological pH.
AB  - The crystal structure of Helicobacter pylori holo-NikR, a Ni(2+)-dependent
      transcription factor, determined at pH 7.3, shows four square-planar nickel
      binding sites, involving one cysteinate and three histidine ligands. This
      observation reconciles previous inconsistencies among calorimetric data,
      structural information at non-physiological pH, and computational studies.

PMID- 21725561
TI  - PEG-templated mesoporous silica nanoparticles exclusively target cancer cells.
AB  - Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug
      delivery carriers, as well as efficient tools for fluorescent cell tracking. The
      major limitation is that MSNs enter cells regardless of a target-specific
      functionalization. Here we show that non functionalized MSNs, synthesized using a
      PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a
      highly specific, receptor mediated, cellular internalization of folic acid (FOL)
      grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing
      cells. Neither the classical clathrin pathway nor macropinocytosis is involved in
      the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through
      aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem
      to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded
      MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative
      (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated
      with MSN-FOL-Cp. The results presented here show that our mesoporous
      nanoparticles do not enter cells unless opportunely functionalized, suggesting
      that they could represent a promising vehicle for drug targeting applications.

PMID- 21725562
TI  - Assembly of a dinuclear silver complex containing an Ag2S2 motif from a
      phosphorus-supported trishydrazone ligand. P=S->Ag(I) coordination.
AB  - The reaction of the phosphorus trihydrazide, (S)P[N(Me)-NH(2)](3) (1) with
      quinoline-2-carboxaldehyde (C(9)H(6)N-2-CHO) in a 1:3 ratio afforded a
      trishydrazone, (S)P[N(Me)-N=CH-2-C(9)H(6)N](3) (2). Crystals of 2 were grown in
      three different solvent media affording an unsolvated (2, monoclinic, P2(1)/n)
      and two solvated (2.3H(2)O, trigonal, R3 and 2.2CH(3)OH, triclinic, P 1) crystal
      forms. Each of these, while possessing an essentially similar molecular
      structure, adopt different crystal packing giving rise to supramolecular
      structures mediated by a variety of weak interactions: O-H-N, O-H-O, C-H-N, C-H
      O, C-H-S, C-H-pi, pi-pi, N-pi and S-pi. The reaction of 2 with
      Ag(ClO(4))(2).6H(2)O in methanol afforded a dinuclear cationic cage
      [Ag{(S)P[N(Me)-N=CH-2-C(9)H(6)N](3)}.ClO(4)](2) (3). The molecular structure of 3
      reveals a dimeric structure consisting of two Ag(I) ions that are held together
      by two ligands. Only two arms of the tris hydrazone ligand are involved in
      coordination while an unprecedented P=S->Ag(I) coordination is seen. This results
      in the formation of an Ag(2)S(2) dimer that is encapsulated by two trishydrazone
      ligands. Both compounds 2 and 3 are photoluminescent.

PMID- 21725563
TI  - Formation and reactivity of the cyclometallated N-heterocyclic carbene complexes
      [Ru(NHC)'(dppe)(CO)H].
AB  - Thermolysis of [Ru(PPh(3))(dppe)(CO)HCl] (dppe = 1,2
      bis(diphenylphosphino)ethane) with the N-heterocyclic carbenes I(i)Pr(2)Me(2)
      (1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene), IEt(2)Me(2) (1,3-diethyl-4,5
      dimethyl-imidazol-2-ylidene) or ICy (1,3-dicyclohexylimidazol-2-ylidene) gave the
      cyclometallated carbene complexes [Ru(NHC)'(dppe)(CO)H] (NHC = I(i)Pr(2)Me(2), 4;
      IEt(2)Me(2), 5; ICy, 6). Dissolution of 4 in CH(2)Cl(2) or CHCl(3) gave the trans
      Cl-Ru-P complex [Ru(I(i)Pr(2)Me(2))'(dppe)(CO)Cl] (7), which converted over hours
      at room temperature to the trans-Cl-Ru-CO isomer 7'. Chloride abstraction from 7
      by NaBPh(4) under an atmosphere of H(2) produced the cationic mono-hydride
      complex [Ru(I(i)Pr(2)Me(2))(dppe)(CO)H][BPh(4)] (9), which could also be formed
      by protonating 4 with 1 eq HBF(4).OEt(2). Treatment of 4 with excess
      HBF(4).OEt(2) followed by extraction into MeCN produced the dicationic
      acetonitrile complex [Ru(I(i)Pr(2)Me(2))(dppe)(CO)(NCMe)(2)][BF(4)](2) (10). The
      structures of 6, 7, 7' and 10 have been determined by X-ray crystallography.

PMID- 21725564
TI  - 1,3-Dipolar cycloaddition between a metal-azide (Ph3PAuN3) and a metal-acetylide
      (Ph3PAuC=CPh): an inorganic version of a click reaction.
AB  - This report describes the synthesis and characterization of 1,5-bis
      triphenylphosphinegold(I) 1,2,3-triazolate (3((1,5))). The synthesis of the
      dinuclear complex 3((1,5)) is achieved via an unprecedented inorganic click
      (iClick) reaction between the metal-azide PPh(3)AuN(3) (1) and the metal
      acetylide PPh(3)Au-C=CPh (2). Characterization of 3((1,5)) includes multinuclear
      NMR spectroscopy, combustion analysis, and single crystal X-ray crystallography.
      Experimental characterization is complemented with density-functional-theory
      (DFT) calculations which indicate the 1,4-isomer 3((1,4)) is less stable by 3.3
      kcal mol(-1). The energetic difference lies primarily in the ability of the
      phenyl group in the 4-position of 3((1,5)) to lie coplanar with the triazolate to
      create a delocalized pi-bonding HOMO orbital.

PMID- 21725565
TI  - Chlorometallate and palladium cluster complexes of wide-span diimine and diamine
      ligands.
AB  - Diimine and diamine ligands that are unable to coordinate to a single metal
      favour the formation of unusual, high-nuclearity Zn chlorometallate and palladium
      chloride complexes.

PMID- 21725566
TI  - Aryl-O reductive elimination from reaction of well-defined aryl-Cu(III) species
      with phenolates: the importance of ligand reactivity.
AB  - Well-defined aryl-Cu(III) species undergo rapid reductive elimination upon
      reaction with phenolates (PhO(-)), to form aryl-OPh cross-coupling products.
      Kinetic studies show that the reaction follows a different mechanistic pathway
      compared to the reaction with phenols. The pH active cyclized pincer-like ligand
      undergoes an initial amine deprotonation that triggers a faster reactivity at
      room temperature. A mechanistic proposal for the enhanced reactivity and the role
      of EPR-detected Cu(II) species will be discussed in detail.

PMID- 21725567
TI  - Multi-residue screening of prioritised human pharmaceuticals, illicit drugs and
      bactericides in sediments and sludge.
AB  - A robust multi-residue method was developed for the analysis of a selection of
      pharmaceutical compounds, illicit drugs and personal care product bactericides in
      sediments and sludges. Human pharmaceuticals were selected for analysis in
      Scottish sewage sludge and freshwater sediments based on prescription, physico
      chemical and occurrence data. The method was suitable for the analysis of the
      selected illicit drugs amphetamine, benzoylecgonine, cocaine, and
      methamphetamine, the pharmaceuticals atenolol, bendroflumethiazide,
      carbamazepine, citalopram, diclofenac, fluoxetine, ibuprofen, and salbutamol, and
      the bactericides triclosan and triclocarban in sewage sludge and freshwater
      sediment. The method provided an overall recovery of between 56 and 128%, RSDs of
      between 2 and 19% and LODs of between 1 and 50 ng g(-1). Using the methodology
      the human pharmaceuticals atenolol, carbamazepine and citalopram and the
      bactericides triclosan and triclocarban were detected in Scottish sewage sludge.
      The illicit drugs cocaine, its metabolite benzoylecgonine, amphetamine and
      methamphetamine were not detected in any of the samples analysed. Triclosan and
      triclocarban were present at the highest concentrations with triclocarban
      detected in all but one sample and showing a pattern of co-occurrence in both
      sludge and sediment samples.

PMID- 21725568
TI  - A bio-inspired micropump based on stomatal transpiration in plants.
AB  - Stomatal transpiration, which is an efficient way to carry water from the roots
      up to the leaves, can be described by "diameter-law". According to the law, the
      flow rate induced by micropore transpiration far exceeded that induced by
      macroscale evaporation, and it can be controlled by opening (or closing) some
      micropores. In this research, a bio-inspired micropump based on stomatal
      transpiration is presented. The micropump is composed of three layers: the top
      layer is a 93 MUm-thick PVC (polyvinylchloride) film with a group of slit-like
      micropores; the second layer is a PMMA sheet with adhesives to join the other two
      layers together; the third layer is a microporous membrane. Using this pump,
      controllable flow rates of 0.13-3.74 MUl min(-1) can be obtained. This micropump
      features high and adjustable flow-rates, simple structure and low fabrication
      cost. It can be used as a "plug and play" fluid-driven unit without any external
      power sources and equipment.

PMID- 21725569
TI  - The theft of host heme by Gram-positive pathogenic bacteria.
AB  - The element iron is essential for bacteria and plays a key role in the virulence
      and pathology of bacterial diseases. The largest reservoir of iron within the
      human body is in protoporphyrin IX, the compound commonly referred to as heme and
      bound by hemoglobin. For many years, the study of heme uptake in bacteria was
      restricted to Gram-negative organisms. However, recent studies have shed light on
      how bacteria containing a thick peptidoglycan, such as Gram-positive bacteria,
      acquire and transport heme. This review summarizes old and new research covering
      the acquisition, transport, and utilization of heme in Gram-positive bacterial
      pathogens.

PMID- 21725570
TI  - One-pot synthesis of benzo[f]quinolin-3-ones and benzo[a]phenanthridein-5-ones by
      the photoanuulation of 6-chloropyridin-2-ones and 3-chloroisoquinolin-1-ones to
      phenylacetylene.
AB  - The one-pot synthesis of benzo[f]quinolin-3-ones and benzo[a]phenanthridein-5
      ones was achieved by the inter- and intramolecular photoannulation of 6
      chloropyridin-2-ones and 3-chloroisoquinolin-1-ones with phenylacetylene or
      tethered phenylacetylene. The reactions were proceeded by photoaddition of 6
      chloropyridin-2-ones and 3-chloroisoquinolin-1-ones to phenylacetylene to give
      the chlorine-substituted stilbenoids, and then 6pi electrocyclization of the
      stilbenoids and oxidation aromatization to afford the polycyclic products.

PMID- 21725571
TI  - Label-free fluorescent detection of thrombin using G-quadruplex-based DNAzyme as
      sensing platform.
AB  - We report herein a label-free and sensitive fluorescent method for detection of
      thrombin using a G-quadruplex-based DNAzyme as the sensing platform. The thrombin
      binding aptamer (TBA) is able to bind hemin to form the G-quadruplex-based
      DNAzyme, and thrombin can significantly enhance the activity of the G-quadruplex
      based DNAzyme. The G-quadruplex-based DNAzyme is found to effectively catalyze
      the H(2)O(2)-mediated oxidation of thiamine, giving rise to fluorescence
      emission. This allows us to utilize the H(2)O(2)-thiamine fluorescent system for
      the quantitative analysis of thrombin. The assay shows a linear toward thrombin
      concentration in the range of 0.01-0.12 nM. The present limit of detection for
      thrombin is 1 pM, and the sensitivity for analyzing thrombin is improved by about
      10,000-fold as compared with the reported colorimetric counterpart. The work also
      demonstrates that thiamine is an excellent substrate for the fluorescence assay
      using the G-quadruplex-based DNAzyme as the sensing platform.

PMID- 21725572
TI  - Validation of electronic structure methods for isomerization reactions of large
      organic molecules.
AB  - In this work the ISOL24 database of isomerization energies of large organic
      molecules presented by Huenerbein et al. [Phys. Chem. Chem. Phys., 2010, 12,
      6940] is updated, resulting in the new benchmark database called ISOL24/11, and
      this database is used to test 50 electronic model chemistries. To accomplish the
      update, the very expensive and highly accurate CCSD(T)-F12a/aug-cc-pVDZ method is
      first exploited to investigate a six-reaction subset of the 24 reactions, and by
      comparison of various methods with the benchmark, MCQCISD-MPW is confirmed to be
      of high accuracy. The final ISOL24/11 database is composed of six reaction
      energies calculated by CCSD(T)-F12a/aug-cc-pVDZ and 18 calculated by MCQCISD-MPW.
      We then tested 40 single-component density functionals (both local and hybrid),
      eight doubly hybrid functionals, and two other methods against ISOL24/11. It is
      found that the SCS-MP3/CBS method, which is used as benchmark for the original
      ISOL24, has an MUE of 1.68 kcal mol(-1), which is close to or larger than some of
      the best tested DFT methods. Using the new benchmark, we find omegaB97X-D and
      MC3MPWB to be the best single-component and doubly hybrid functionals
      respectively, with PBE0-D3 and MC3MPW performing almost as well. The best single
      component density functionals without molecular mechanics dispersion-like terms
      are M08-SO, M08-HX, M05-2X, and M06-2X. The best single-component density
      functionals without Hartree-Fock exchange are M06-L-D3 when MM terms are included
      and M06-L when they are not.

PMID- 21725573
TI  - Metal-based antitumour drugs in the post-genomic era: what comes next?
AB  - In our Dalton Transactions Perspective article entitled, 'Metal-based antitumour
      drugs in the post genomic era', (Dalton Trans., 2006, 1929-1933) we discussed
      metal-based drugs in light of past decades of research. We concluded that the
      post-genomic era would dictate a change in the direction of the field with
      knowledge of the genome increasingly allowing protein targets to be identified
      and not simply assuming that DNA is the only relevant target of metal-based
      drugs. Since our article was published new insights into the mode of action of
      metal-based drugs have emerged making some older findings increasingly relevant
      to current drug design. In this article we discuss these developments in terms of
      what we believe should be the future direction for the field.

PMID- 21725574
TI  - Reaction of bis(o-phosphinophenyl)silane with M(PPh3)4 (M = Ni, Pd, Pt):
      synthesis and structural analysis of eta2-(Si-H) metal(0) and pentacoordinate
      silyl metal(II) hydride complexes of the Ni triad bearing a PSiP-pincer ligand.
AB  - Reactions of bis(o-(diphenylphosphino)phenyl)methylsilane with M(PPh(3))(4) (M =
      Ni, Pd, Pt) were investigated. When M = Ni or Pd, synthesis and isolation of
      eta(2)-(Si-H) complexes of mononuclear Ni(0) and Pd(0) were achieved for the
      first time as frozen intermediates for oxidative addition of the Si-H bond.
      Structural analysis by X-ray and NMR spectroscopy disclosed that their eta(2)-(Si
      H) structures were maintained in both solid and solution states and coordination
      of the Si-H bond to the metal center was relatively weak. On the other hand,
      reaction with a platinum(0) complex afforded two kinds of pentacoordinate silyl
      platinum(II) hydride complexes having a PSiP-pincer ligand, which underwent
      unique thermal isomerization from a square-pyramidal cis-H-Pt-Si to a trigonal
      bipyramidal trans-H-Pt-Si isomer. Mechanistic investigations revealed that this
      isomerization proceeded via an intramolecular rearrangement process probably
      through a turnstile rotation.

PMID- 21725575
TI  - Highly efficient enzymatic synthesis of 3'-deoxyapionucleic acid (apioNA) having
      the four natural nucleobases.
AB  - The synthesis of the 3'-deoxyapionucleoside 3''-triphosphates (apioNTPs) having
      the four natural nucleobases and their enzymatic incorporation into a DNA-DNA
      primer-template have been tried. Therminator DNA polymerase was shown to
      incorporate these apioNTPs effectively giving 43mer DNA-apioNA chimera.

PMID- 21725576
TI  - A 4-hydroxynaphthalimide-derived ratiometric fluorescent chemodosimeter for
      imaging palladium in living cells.
AB  - A highly selective ratiometric fluorescent chemodosimeter derived from 4
      hydroxynaphthalimide was designed and synthesized to image palladium species in
      living cells by virtue of a palladium-catalyzed depropargylation reaction, and it
      could monitor three typical palladium species (0, + 2 and + 4) without additional
      reagents.

PMID- 21725577
TI  - Short-range correlations in d-f cyanido-bridged assemblies with XY and XY
      Heisenberg anisotropy.
AB  - Two new d-f cyanido-bridged 1D assemblies [RE(pzam)(3)(H(2)O)Mo(CN)(8)].H(2)O (RE
      = Sm(III), Er(III)) were synthesized and their magneto-structural properties have
      been studied by field-dependent magnetization and specific heat measurements at
      low temperatures (>=0.3 K). Below ~ 10 K the ground state of both the Sm(III) and
      Er(III) ions is found to be a Kramers doublet with effective spin S = 1/2. From
      analyses of the low-temperature magnetic specific heat and magnetization the
      exchange coupling between these RE(III) effective spins and the Mo(v) spins S =
      1/2 along the structural chains has been determined. It is found to be
      antiferromagnetic, with J(?)/k(B) = -2.6 K and Ising-Heisenberg symmetry of the
      interaction (J(?)/J(?) = 0.3) for RE = Sm(III), whereas the compound with RE =
      Er(III) behaves as a pure XY chain, with J(?)/k(B) = -1.0 K. For the compound
      [Sm(pzam)(3)(H(2)O)Mo(CN)(8)].H(2)O a small lambda-type anomaly in the specific
      heat is observed at about 0.6 K, which is ascribed to a transition to long-range
      magnetic ordering induced by weak interchain interactions of dipolar origin. No
      evidence for 3D interchain magnetic ordering is found in the Er(III) analogue.

PMID- 21725578
TI  - Two different fibrinogen gene mutations associated with bleeding in the same
      family (A alphaGly13Glu and gammaGly16Ser) and their impact on fibrin clot
      properties: fibrinogen Krakow II and Krakow III.

PMID- 21725579
TI  - The pharmacokinetic diversity of two von Willebrand factor (VWF)/ factor VIII
      (FVIII) concentrates in subjects with congenital von Willebrand disease. Results
      from a prospective, randomised crossover study.
AB  - The pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII
      (FVIII) concentrates are important for treatment efficacy and safety of von
      Willebrand disease (VWD) patients. This prospective, head-to-head, randomised
      crossover study compared the PK profile of a new, high purity, human plasma
      derived (pd)VWF/FVIII concentrate, Wilate, with the PK profile of an intermediate
      purity (pd)VWF/FVIII concentrate, Humate-P, in VWD patients. Subjects with
      inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF
      ristocetin cofactor activity [VWF:RCo]) of Wilate or Humate-P in Period 1, and
      switched to the other study drug in Period 2. Each period was preceded by a
      washout time of >= 7 days. Coagulation factor parameters were analysed at
      multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles,
      which indicated comparability for VWF antigen and VWF:RCo between Wilate and
      Humate-P. The reported VWF:RCo average and terminal t1/2 of 10.4 and 15.8 hours
      (h), respectively, for Wilate and 9.3 h and 12.8 h for Humate-P, were not
      statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate 1.89,
      Humate-P 1.99 IU/dl per IU/kg) were similar between the two replacement
      therapies. Wilate showed parallel decay curves for VWF:RCo and FVIII clotting
      activity (FVIII:C) over time, while FVIII:C of Humate-P displayed a plateau
      between 0 and 12-24 h. This study demonstrated bioequivalent PK properties for
      VWF between Wilate and Humate-P. The PK profile of Wilate, combined with the 1:1
      VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring
      of VWF replacement to prevent bleeding in individuals with VWD.

PMID- 21725580
TI  - Seasonal and monthly variability in the incidence of venous thromboembolism. A
      systematic review and a meta-analysis of the literature.
AB  - Many studies showed that the occurrence of cardiovascular and cerebrovascular
      events exhibits a seasonal and monthly variation. Evidences of a seasonal and
      monthly variation in the incidence of venous thromboembolism (VTE) are more
      conflicting. We conducted a systematic review and a meta-analysis of the
      literature to assess the presence of an infradian rhythm of this disease. MEDLINE
      and EMBASE databases were searched up to January 2010. Monthly and seasonal
      variation in the incidence of VTE were analysed. We included studies analysing
      seasonal or monthly aggregation in the incidence of deep-vein thrombosis (DVT)
      and/or pulmonary embolism (PE) with an objective diagnosis of VTE. Two authors
      independently reviewed and extracted data. Seventeen studies for a total of about
      35,000 patients were included. Twelve studies analysed the seasonal variation and
      10 studies the monthly variation of VTE. Our results showed a significantly
      increased incidence of VTE in winter (chi-square 146.04, p <0.001), with a
      relative risk (RR) of VTE of 1.143 (99% CI [1.141, 1.144]), and a significantly
      increased incidence of VTE in January (chi-square 232.57, p <0.001) with an RR of
      VTE of 1.194 (99% CI 1.186, 1.203). Subgroup analyses including only idiopathic
      venous thromboembolic events confirmed the results of principal analyses. In
      conclusion, our data support the presence of an infradian pattern in the
      incidence of venous thromboembolic events, with a significantly higher risk in
      Winter and in January. Future studies are needed to better clarify the mechanisms
      behind this pattern.

PMID- 21725581
TI  - Platelet reactivity is a stable and global phenomenon in aspirin-treated
      cardiovascular patients.
AB  - In healthy subjects, platelet hyperreactivity is a global phenomenon--as opposed
      to agonist-specific--and epinephrine-induced platelet aggregation (EPA) is a
      reliable marker of this phenotype. Few data are available on platelet reactivity
      and the relationship between EPA and aggregation induced by other agonists in
      cardiovascular patients. It was the objective of this study to characterise
      platelet reactivity in stable cardiovascular patients treated with aspirin and to
      derive a composite index integrating several aggregation pathways, suitable for
      selecting patients with extreme phenotypes for further proteomics analysis.
      Platelet reactivity to agonists was assessed in 110 patients twice, two weeks
      apart. Factorial analysis was used to determine whether the results obtained with
      the different agonists could be summarised in a single composite index. EPA
      correlated with the aggregation values obtained with each of the other agonists,
      with correlation coefficients of 0.44 to 0.55 (p < 0.001). We constructed a
      composite "platelet reactivity" index that included 60% of the information
      provided by each agonist. The results obtained at the first patient visit were
      consistent with those obtained at the second visit (r = 0.78, p<0.01). No
      clinical or biological parameters correlated with the composite index. The
      extreme phenotypes of six selected subjects were confirmed 12 months after the
      second visit. In conclusion, platelet reactivity in aspirin-treated
      cardiovascular patients is a global phenomenon that can be summarised by a
      composite index based on the aggregation responses to various agonists and
      integrating several activation pathways. This index is not dependent on clinical
      or biological variables, suggesting that genetic factors regulate platelet
      reactivity in these patients.

PMID- 21725583
TI  - Factors influencing the decision to extend working life or retire.
AB  - OBJECTIVE: The aim of this study was to evaluate factors within nine identified
      areas that influence why some older workers want to (or believe they can) work
      until age 65 years or beyond, whereas others leave the workforce earlier.
      METHODS: The questionnaire-based, cross-sectional study included 1792 respondents
      aged 55-64 years, employed in the healthcare sector in Sweden. Using logistic
      regression, we investigated the associations between statements within nine areas
      and two outcome measures: (i) whether the individual wanted to work until age 65
      years or beyond and (ii) whether the individual believed they can work until age
      65 years or beyond. RESULTS: Of the 1792 respondents, 54% stated that they "can"
      and 38% that they "want to" work until age 65 years or beyond. Three areas were
      significantly associated with both these outcomes: worker health, economic
      incentives, and retirement decisions by life partners or close friends. Mental
      and physical working environment, work pace and skills/competence were associated
      with the "can" outcome, whereas work as an important part of life, working time,
      and management attitude to older workers were associated with the "want to"
      outcome. CONCLUSION: Although there were differences regarding the associations
      between six of the areas and the two outcomes (ie, "can" and "want to" go on
      working until age 65 years or beyond), three of the areas were important to both
      outcomes. Among those, it was interesting that life partner or close social
      environment gave higher odds ratios than for example health, physical work
      environment, or work satisfaction.

PMID- 21725582
TI  - Massive thrombus burden with recurrence of intracoronary thrombosis early after
      stenting and delayed onset of prasugrel action in a patient with ST-elevation
      myocardial infarction and cardiac shock.

PMID- 21725584
TI  - Achromic superficial spreading melanoma accidentally treated with imiquimod.

PMID- 21725585
TI  - Cobalt protoporphyrin induces differentiation of monocytic THP-1 cells through
      regulation of cytoplasmic Ref-1-related NADPH oxidase activity.
AB  - Cobalt protoporphyrin (CoPP) is a potent and effective metalloporphyrin inducer
      of heme oxygenase-1 (HO-1) activity in many tissues. Here, we report that CoPP
      induces differentiation of monocytic THP-1 cells into macrophage-like cells. CoPP
      induced a marked growth inhibition with a slight reduction in viability, and
      increased adhesion and spreading of THP-1 cells. However, other protoporphyrins
      did not. CoPP also resulted in expression of CD11b, MMP9, MSR1, CD14 and ICAM-1,
      which are differentiation markers for macrophages. Interestingly, we observed a
      decrease of cytoplasmic redox factor-1 (Ref-1) levels in the process of CoPP
      induced differentiation of THP-1 cells. In addition, knockdown of Ref-1 by siRNA
      enhanced cell adhesion induced by CoPP. Furthermore, an inhibitor of NADPH
      oxidase, diphenyleneiodonium (DPI), completely abolished CoPP-induced adhesion of
      Ref-1-deficient cells using an siRNA. A cytosolic factor for NADPH oxidase
      activity, p47phox, was significantly increased in THP-1 cells by CoPP treatment.
      Kappanockdown of Ref-1 increased CoPP-induced p47phox expression in THP-1 cells.
      Taken together, these results suggest that CoPP induces differentiation of
      monocytic THP-1 cells, and that the CoPP-induced differentiation is associated
      with cytoplasmic Ref-1-related NADPH oxidase activity.

PMID- 21725586
TI  - An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein
      B mRNA-editing enzyme-catalytic polypeptide-like 3G.
AB  - Human apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC)
      3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the
      antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory
      function of Vif is related to its ability to degrade A3G in the proteasome. This
      finding prompted us to examine the activities of 4-(dimethylamino)-2,6-bis[(N-(2
      [(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine (SN-2) and SN-3. We found that
      5 uM SN-2 increases the expression of A3G to a level much higher than that
      observed in the absence of Vif, without affecting the level of Vif expression.
      The proteasome inhibitor MG-132 increased the level of both A3G and Vif
      expression. These results demonstrate that A3G is ubiquitinated and degraded in
      the proteasome by a factor other than Vif, and that SN-2 selectively inhibits
      these processes. Furthermore, 5 uM SN-2 significantly inhibited the MAGI cell
      infectivity of wild-type HIV-1. These findings may contribute to the development
      of a novel anti-HIV-1 drug.

PMID- 21725587
TI  - Comparative analysis of proteins in the culture supernatants of human intestinal
      epithelial cells infected with the wild-type and rtxE mutant of Vibrio
      vulnificus.
AB  - Bacterial virulence factors and secreted extracellular proteins from damaged host
      cells following infection have been recognized as key mediators in the
      pathophysiological alterations observed in septic shock, and have also been shown
      to have a synergistic influence on bacterial pathogenicity. We hypothesized that
      during infections, virulence factors as well as host-shed proteins may
      synergistically influence aspects of the pathogenicity of V. vulnificus, such as
      primary septic shock and overproduction of proinflammatory cytokines. However,
      virulence factors and host-derived proteins have yet to be clearly evaluated
      during V. vulnificus infection. In this study, we analyzed and compared the
      proteins in conditioned supernatants generated from co-cultures of host cells and
      either wild-type or rtxE mutant V. vulnificus using LC-QTOF-MS/MS analysis. In a
      previous study, we determined that the culture supernatants of the rtxE mutant V.
      vulnificus-infected INT-407 cells induced significantly lower levels of IL-8
      production from human intestinal epithelial cells than did the culture
      supernatants of wild-type V. vulnificus-infected INT-407 cells. LC-QTOF-MS/MS
      analysis results demonstrated that levels of proteins such as HSP90 alpha/beta,
      14-3-3 gamma, PRX II, hnRNP K, beta-actin, alpha-tubulin and V. vulnificus
      flagellin were significantly lower in the culture supernatants of rtxE mutant V.
      vulnificus-infected INT-407 cells than in the culture supernatants of wild-type
      V. vulnificus-infected INT-407 cells. These results demonstrate that V.
      vulnificus RTX toxins acting via rtxE, a transporter of virulence factors, play a
      very important role in the pathogenesis of V. vulnificus, as well as in its
      initial role in inducing pathogenic mediators from host cells.

PMID- 21725588
TI  - Inhibition of multiplication of herpes simplex virus by caffeic acid.
AB  - Hot water extracts of coffee grinds and commercial instant coffee solutions have
      been shown to exhibit marked antiviral and virucidal activities against herpes
      simplex virus type 1 (HSV-1). Specifically, it has been shown that caffeine and N
      methyl-pyridinium formate inhibit the multiplication of HSV-1 in HEp-2 cells. The
      present study examined the virological properties and the antiviral activity of
      caffeic acid against HSV-1. Caffeic acid inhibited the multiplication of HSV-1 in
      vitro, while chlorogenic acid, a caffeic acid ester with quinic acid, did not.
      These reagents did not have a direct virucidal effect. The one-step growth curve
      of HSV-1 showed that the addition of caffeic acid at 8 h post infection (h p.i.)
      did not significantly affect the formation of progeny viruses. An analysis of the
      influence of the time of caffeic acid addition, revealed that addition at an
      early time post infection remarkably inhibited the formation of progeny
      infectious virus in the infected cells, but its addition after 6 h p.i. (i.e.,
      the time of the completion of viral genome replication) did not efficiently
      inhibit this process. These results indicate that caffeic acid inhibits HSV-1
      multiplication mainly before the completion of viral DNA replication, but not
      thereafter. Although caffeic acid showed some cytotoxicity by prolonged
      incubation, the observed antiviral activity is likely not the secondary result of
      the cytotoxic effect of the reagent, because the inhibition of the virus
      multiplication was observed before appearance of the notable cytotoxicity.

PMID- 21725589
TI  - Sequence confirmation and characterization of the mouse Ssxa gene: Ssxa protein
      is cleaved and the N-terminal cleaved fragment translocates into the nucleus.
AB  - This is the first demonstration of a stop codon in the sequence of mouse Ssxa and
      characterization of the biological behavior of Ssxa protein. Cancer testis
      antigen (CTA) is known as a target of immunotherapy against cancer, and Ssxa is
      one of the CTAs. Although a CTA would be useful to establish a mouse cancer
      vaccine model using endogenous antigen, the stop codon was not identified in the
      sequence of Ssxa cDNA that was previously reported. In this study, the gene
      sequence of Ssxa was different from the previous report in which several mouse
      CTAs were analyzed. Initially, we identified the correct cDNA sequence of mouse
      Ssxa by 3'-rapid amplification of cDNA ends and found a new exon containing the
      stop codon (Exon X). Ssxa mRNA expression was determined by reverse transcription
      PCR (RT-PCR) in four mouse cancer cell lines and the testis but not in other
      normal organs. We found that the molecular weight of recombinant Ssxa protein is
      12 kDa, and we generated an anti-Ssxa antibody which recognizes the C-terminus of
      Ssxa. Two vectors expressing fusion proteins (pSsxa-GFP and pGFP-Ssxa) were
      generated and fluorescence in the nucleus was observed only in the pGFP-Ssxa
      transfected cells. Therefore, we conclude that the N-terminal cleaved fragment of
      Ssxa, which has a KRAB domain (nuclear localization signal), translocates into
      the nucleus after cleavage of the C-terminus.

PMID- 21725590
TI  - The role of gC1qR in regulating survival of human papillomavirus 16 oncogene
      transfected cervical cancer cells.
AB  - Human papillomavirus 16 (HPV-16) is strongly associated with the development of
      50% of cervical cancers. The E6 and E7 proteins encoded by high-risk HPV types
      are associated with the immune evasion of cervical cancer cells, but the
      mechanism is poorly understood. The purpose of this study was to investigate
      whether cells transfected with E6 and E7 expression constructs reduce the
      expression of the globular heads of the C1q receptor (gC1qR), a mitochondrial
      surface protein overexpressed in certain cancer cells. First, C-33A cells were
      transiently transfected with the HPV-16 E6 and E7 oncogenes which resulted in
      gC1qR inhibition and a reduction in apoptosis. Second, gC1qR overexpression in
      cells showed that caspase-3 activation and mitochondrial dysfunction were
      involved in gC1qR-induced apoptosis. Cells transfected with a GFP-gC1qR vector
      resulted in upregulated gC1qR protein and a gradual increase in the generation of
      reactive oxygen species (ROS). Additionally, ROS generation and increased Ca2+
      influx in mitochondria resulted in the loss of the mitochondrial transmembrane
      potential. Interestingly, when gC1qR was overexpressed in C-33A cells, apoptosis
      was significantly inhibited when cells were treated with metformin, which may
      protect mitochondrial function. These data suggest that gC1qR could play an
      important role in HPV-16-induced cervical cancer immune evasion depending on its
      level of expression and subcellular localisation.

PMID- 21725591
TI  - PhotolonTM --photosensitization induces apoptosis via ROS-mediated cross-talk
      between mitochondria and lysosomes.
AB  - The localization of photosensitizers in the subcellular compartments during
      photodynamic therapy (PDT) plays a major role in the cell destruction; therefore,
      the aim of this study was to investigate the intracellular localization of
      Chlorin e6-PVP (PhotolonTM) in malignant and normal cells. Our study involves the
      characterization of the structural determinants of subcellular localization of
      Photolon, and how subcellular localization affects the selective toxicity of
      Photolon towards tumor cells. Using confocal laser scanning microscopy (CLSM) and
      fluorescent organelle probes; we examined the subcellular localization of
      PhotolonTM in the murine colon carcinoma CT-26 and normal fibroblast (NHLC)
      cells. Our results demonstrated that after 30 min of incubation, the distribution
      of Photolon was localized mainly in the cytoplasmic organelles including the
      mitochondria, lysosomes, Golgi apparatus, around the nuclear envelope and also in
      the nucleus but not in the endo-plasmic reticulum whereas in NHLC cells, Photolon
      was found to be localized minimally only in the nucleus not in other organelles
      studied. The relationship between subcellular localization of Photolon and PDT
      induced apoptosis was investigated. Apoptotic cell death was judged by the
      formation of known apoptotic hallmarks including, the phosphatidylserine
      externalization (PS), PARP cleavage, a substrate for caspase-3 and the formation
      of apoptotic nuclei. At the irradiation dose of 1 J/cm2, the percentage of
      apoptotic cells was 80%, respectively. This study provided substantial evidence
      that Photolon preferentially localized in the subcellular organelles in the
      following order: nucleus, mitochondria, lysosomes and the Golgi apparatus and
      subsequent photodamage of the mitochondria and lyso-somes played an important
      role in PDT-mediated apoptosis CT-26 cells. Our results based on the cytoplasmic
      organelles and the intranuclear localization extensively enhance the efficacy of
      PDT with appropriate photosensitizer and light dose and support the idea that PDT
      can contribute to elimination of malignant cells by inducing apoptosis, which is
      of physiological significance.

PMID- 21725592
TI  - Protein-based nanotechnology: antibody conjugated with photosensitizer in
      targeted anticancer photoimmunotherapy.
AB  - Photodynamic therapy (PDT) is a minimally invasive cancer therapy that depends on
      the buildup of a photosensitizing drug within targeted tissue. The
      photosensitizer is subsequently activated by light of a specific wavelength,
      resulting in destruction of the targeted tissue by free radicals or singlet
      oxygen. Successful treatment requires delivery of critical amounts of drug into
      the cancerous tissue. This frequently demands high doses of the drug in the
      circulatory system that could lead to side effects in normal daylight due to
      accumulation of photodrug in normal tissue. To reduce drug load we explored the
      possibility of targeting cancer with antibody conjugated with photosensitizer. As
      a model we used LnCAP human prostate cancer cells targeted by antibody (against
      prostate-specific membrane antigen) which was conjugated with hematoporphyrin
      (HP). Our results show clearly that mAb/HP conjugates can deliver HP to the tumor
      cells which would result in considerably less HP in the circulation and,
      therefore, lower the delivery of HP to normal tissue, resulting in fewer side
      effects.

PMID- 21725593
TI  - Identification of senescence-inducing microRNAs in normal human keratinocytes.
AB  - MicroRNAs (miRNAs) are epigenetic regulators of eukaryotic gene expression and
      play key roles in many cellular processes. However, the role of miRNAs for
      replicative senescence of normal human keratinocytes (NHKs) remains unknown.
      Thus, we examined the expression profiles of 847 miRNAs in exponentially
      replicating and senescent NHKs and identified 126 senescence-associated miRNAs
      (SA-miRs). Among SA-miRs, 117 miRNAs (93%) were upregulated and 9 miRNAs (7%)
      were downregulated in senescent NHKs compared to those of exponentially
      replicating cells. Among the above miRNAs, we selected two miRNAs, miR-137 and
      miR-668, for further investigation because they were consistently upregulated
      with replicative senescence of three independent NHK cultures. Ectopic
      overexpression of miR-137 or miR-668 induced senescence in rapidly proliferating
      NHKs; a notable increase in senescence-associated beta-galactosidase activity,
      p16INK4A and p53 was observed, indicating that they are novel senescence-inducing
      miRNAs. In addition, these senescence-inducing miRNAs were gradually increased
      during organismal aging of normal human oral epithelia. We also detected
      downregulation of miR-137 and miR-668 in many tested human head and neck squamous
      cell carcinoma cell lines. Since senescence would be viewed as a potent tumor
      suppressive pathway, the newly identified senescence-inducing miRNAs deserve to
      be further investigated for their therapeutic application in cancer treatment.

PMID- 21725594
TI  - Combined effect of polymorphisms in Rad51 and Xrcc3 on breast cancer risk and
      chromosomal radiosensitivity.
AB  - Enhanced in vitro chromosomal radiosensitivity (CRS) has been proposed as a
      marker for low-penetrance gene mutations predisposing to breast cancer (BC).
      Since the double strand break (DSB) is the most detrimental form of DNA damage
      induced by ionizing radiation, it is possible that mutations in genes encoding
      proteins involved in DSB repair affect breast cancer risk. The purpose of the
      present study was to examine whether five single nucleotide polymorphisms (SNPs)
      in Rad51 and Xrcc3 (rs1801320, rs1801321, rs1799796, rs861539 and rs1799794)
      exhibited an association with breast cancer susceptibility in a Belgian
      population of BC patients with a known or putative genetic predisposition. We
      also ascertained whether a relationship exists between the occurrence of the
      variant alleles of these variations and in vitro CRS. Blood samples were obtained
      from BC patients and from the control population that included healthy female
      individuals. Variations in the 5' UTR of Rad51 and Xrcc3 were genotyped, and
      statistical analysis was performed. The results showed that low-penetrant
      variations in Rad51 and Xrcc3, two proteins belonging to the homologous
      recombination DSB repair pathway, may modify BC risk in patients already carrying
      a pathological mutation in the highly penetrant BC genes BRCA1 and BRCA2.
      Combined risk genotype analysis revealed that Rad51 SNPs enhance BC risk in BRCA2
      patients, whereas Xrcc3 SNPs significantly enhance BC risk in carriers of BRCA1
      mutations and in patients with hereditary BC. When four putative risk genotypes
      of Rad51 and Xrcc3 were combined, positive significant odds ratios were obtained
      in the entire patient population and in patients with a hereditary history of
      disease. Although obtained from a limited number of patients, our data are
      supportive of a polygenic model whereby combinations of weak variations are
      responsible for an enhanced BC risk by acting jointly with high-penetrant
      mutations in BRCA1 or BRCA2.

PMID- 21725595
TI  - Reversal of redox-dependent inhibition of diacylglycerol kinase by antioxidants
      in mesangial cells exposed to high glucose.
AB  - Activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway is one of
      the pathomechanisms of diabetic nephropathy. We previously reported that d-alpha
      tocopherol, well known as an antioxidant, enhances diacylglycerol kinase (DGK)
      activity, leading to the reduction of excess DAG accumulation and PKC activation
      in the glomeruli of streptozotocin-induced diabetic rats. However, it remains to
      be determined whether the effect of d-alpha-tocopherol on DGK activity is exerted
      through its antioxidative action. DAG contents, PKC and membranous DGK activity
      were measured in cultured human glomerular mesangial cells under normal (5.5 mM)
      or high glucose (27.5 mM) conditions in the presence or absence of two
      antioxidants (50 MUM d-alpha-tocopherol and probucol). Mesangial cells were
      exposed to hydrogen peroxide (H2O2) (10-1000 MUM) in the presence or absence of
      300 U/ml catalase, followed by measurement of DGK activity. Both antioxidants
      restored the high glucose-induced decrease in DGK activity, resulting in the
      reduction of high glucose-induced activation of the DAG-PKC pathway. In mesangial
      cells exposed to H2O2 at various concentrations, DGK activity decreased in a dose
      dependent manner. The addition of antioxidative enzyme catalase to the cells
      reversed the H2O2-mediated down-regulation of DGK activity. In conclusion, DGK
      activity is reduced by oxidative stress in human mesangial cells cultured under
      high glucose conditions. Antioxidants, including d-alpha-tocopherol and probucol
      may improve hyperglycemia-induced DAG-PKC activation by enhancing DGK activity.

PMID- 21725596
TI  - A novel chimeric DNA vaccine: enhancement of preventive and therapeutic efficacy
      of DNA vaccine by fusion of Mucin 1 to a heat shock protein 70 gene.
AB  - Intensive efforts to improve vaccines against cancer are currently outgoing.
      Mucin 1 (Muc1) is a tumor-specific antigen that is overexpressed and heavily
      glycosylated in a variety of adenocarcinomas. In the present study, the efficacy
      of an anticancer DNA vaccination strategy was demonstrated using Muc1 fusion
      vaccines. To enhance antigen presentation and tumor-suppressive efficacy, a
      chimeric Muc1 vaccine was designed, encoding the transmembrane- and C-terminal
      domain-deleted Muc1 gene (?TM) fused to the human HSP70 gene. To confirm the
      expression and secretion of fusion protein, cell culture supernatants were
      subjected to Western blotting. We found secreted Muc1 DeltaTM-HSP0 fusion protein
      in the supernatants. These results demonstrate that the Muc1 DeltaTM-HSP0
      construct can be efficiently expressed and secreted from transfected cells. When
      the chimeric Muc1 vaccine was administered to mice, antigen-specific cellular
      immune responses were observed. Notably, we observed that antigen-specific
      lymphocyte proliferation and cytotoxic responses were effectively induced only in
      the group of mice that had been vaccinated with the chimeric Muc1 vaccine.
      Concurrent with the Muc1-specific tumor-suppressive effect, the growth of
      established Muc1-expressing B16 mouse melanoma cells was also significantly
      inhibited by vaccination with the chimeric Muc1 vaccine. The growth of B16 mouse
      melanoma cells expressing human Muc1 in C57BL/6 mice was effectively suppressed
      by the Muc1-HSP70 chimeric DNA vaccine. Our results reveal that the antitumor
      efficacy of the chimeric DNA vaccine was improved by the presence of HSP/70.

PMID- 21725597
TI  - The set gene is a potential oncogene in human colorectal adenocarcinoma and oral
      squamous cell carcinoma.
AB  - The purpose of this study was to determine whether set gene plays a role in the
      tumorigenesis of human colorectal adenocarcinoma and oral squamous cell
      carcinoma. We used the human colon carcinoma cell line Ls174 and oral squamous
      cell carcinoma cell line HSC3 to evaluate the effect of set suppression on cancer
      cell proliferation and apoptosis. Using real-time PCR, we examined set gene
      expression in human colorectal adenocarcinoma tissues and matched normal
      colorectal tissues. Thirty pairs of colorectal adenocarcinoma tissues and matched
      normal colorectal tissues were used for real-time PCR. We transfected human colon
      carcinoma cell line Ls174 and oral squamous cell carcinoma cell line HSC3 with
      siRNA against the set gene. The effect of set gene suppression on cancer cell
      proliferation and apoptosis were studied by MTT assay and flow cytometry. Real
      time PCR indicated that set gene expression was up-regulated in 70% of tumor
      samples (21 out of 30 samples). siRNA2 sequences significantly decreased set mRNA
      levels in Ls174 and HSC3 cells. The inhibitory rate in the two cell lines was
      55.91 and 71.57%, respectively. MTT assay revealed a 21.4% inhibition on cell
      proliferation in HS174 cells and a 20.2% inhibition in HSC3 cells. Flow cytometry
      data indicated that the cell apoptosis rate was 18.37% in Ls174 cells and 17.97%
      in HSC3 cells; these rates were significantly higher than those of the control
      groups. In conclusion, the set gene was found to play a role in the tumorigenesis
      of human colorectal adenocarcinoma. It may promote tumorigenesis by enhancing
      cancer cell proliferation and inhibiting cancer cell apoptosis.

PMID- 21725598
TI  - Effect of 4-methyl-3-nitrobenzoic acid on non-small cell lung cancer cell
      migration.
AB  - Metastasis is a major cause of mortality among lung cancer patients. In a
      previous high-throughput screening of 20,000 compounds to identify inhibitors of
      cancer cell migration, 4-methyl-3-nitrobenzoic acid was found to inhibit the
      migration of nine tumor cell lines. The present study used the human non-small
      cell lung cancer cell (NSCLC) treatment with 4-methyl-3-nitrobenzoic acid
      significantly inhibited epithelial growth factor (EGF)-induced chemotaxis and
      chemokinesis of cancer cells in NSCLC cells. The defect in chemotaxis is likely
      due to the impairment in EGF-induced cofilin phosphorylation and actin
      polymerization. Furthermore, EGF-induced cell adhesion, which is another key
      factor in cell migration, was also inhibited. Taken together, these results
      suggest that 4-methyl-3-nitrobenzoic acid is a potent inhibitor of cancer cell
      chemotaxis and may be developed into a novel antimetastasis drug.

PMID- 21725599
TI  - ShRNA-mediated gene silencing of heat shock protein 70 inhibits human colon
      cancer growth.
AB  - Heat shock protein 70 (Hsp70), a chaperone involved in tumor progression, is
      overexpressed in various human tumors. However, its role in colon cancer
      progression is not completely understood. In the present study, two shRNA plasmid
      vectors against Hsp70 were constructed and stably transfected into the colon
      cancer cell line HT29 to determine the effect of Hsp70 on cell proliferation,
      cell cycle distribution and cell apoptosis in HT29 cells in vitro, and its effect
      on xenograft tumor growth and apoptosis in vivo. Cell proliferation was
      determined using MTT assay. The results revealed that Hsp70 silencing efficiently
      inhibited the growth of HT29 cells in culture, induced cell cycle arrest at the
      G1 phase, and significantly increased apoptosis. Moreover, stable clones from the
      Hsp70 shRNA-2 vector suppressed xenograft tumor growth and enhanced apoptosis in
      vivo compared with a mock and vector control group. In conclusion, specific Hsp70
      shRNA silencing may inhibit colon cancer growth, indicating that Hsp70 silencing
      is a potential therapeutic strategy for the treatment of colon cancer.

PMID- 21725600
TI  - Differential expression profiles of the Hedgehog signaling pathway between
      microsatellite-stable and microsatellite-unstable colorectal cancers.
AB  - The present study aimed to investigate the expression of the Hedgehog (Hh)
      signaling pathway between microsatellite-unstable (MSI) and microsatellite
      unstable (MSS) colorectal cancers (CRCs). A total of 61 samples of CRC tissue and
      corresponding blood samples were obtained from the surgical department of our
      hospital. The tissue samples were examined by immunohistochemistry using
      antibodies against Sonic Hh (SHH), Pathed (PTCH) and Gli1, and evaluated
      independently for protein expression by two pathologists blinded to clinical
      outcome. Based on the immunohistochemistry results, SHH and PTCH expression
      varied in terms of histological type. In mucinous adenocarcinoma (MA) Hedgehog
      signaling was not highly expressed. There were more significant differences in
      the expression of SHH and PTCH (P<0.05), compared with Gli1. Moreover,
      significant differences were found in the expression of SHH, Gli1 and PTCH
      between the MSI and MSS groups (P<0.05). Hedgehog signals were more frequently
      expressed in the MSI group compared with the MSS group. In conclusion, this study
      indicates that the expression of the Hh signaling pathway may play a significant
      role in MSI in colorectal cancer.

PMID- 21725601
TI  - Effects of TGF-beta signaling blockade on human A549 lung adenocarcinoma cell
      lines.
AB  - Transforming growth factor beta (TGF-beta) is overexpressed in a wide variety of
      cancer types including lung adenocarcinoma (LAC), and the TGF-beta signaling
      pathway plays an important role in tumor development. To determine whether
      blockade of the TGF-beta signaling pathway can inhibit the malignant biological
      behavior of LAC, RNA interference (RNAi) technology was used to silence the
      expression of TGF-beta receptor, type II (TGFbetaRII) in the LAC cell line, A549,
      and its effects on cell proliferation, invasion and metastasis were examined.
      Three specific small interfering RNAs (siRNAs) designed for targeting human
      TGFbetaRII were transfected into A549 cells. The expression of TGFbetaRII was
      detected by Western blot analysis. Cell proliferation was measured by MTT and
      clonogenic assays. Cell apoptosis was assessed by flow cytometry. The invasion
      and metastasis of A549 cells were investigated using the wound healing and
      Matrigel invasion assays. The expression of PI3K, phosphorylated Smad2, Smad4,
      Akt, Erk1/2, P38 and MMPs was detected by Western blot analysis. The TGFbetaRII
      siRNA significantly reduced the expression of TGFbetaRII in A549 cells. The
      knockdown of TGFbetaRII in A549 cells resulted in the suppression of cell
      proliferation, invasion and metastasis and induced cell apoptosis. In addition to
      the Smad-dependent pathway, independent pathways including the Erk MAPK, PI3K/Akt
      and p38 MAPK pathways, as well as the expression of MMPs and VEGF, were
      inhibited. In conclusion, TGF-beta signaling is required for LAC progression.
      Therefore, the blockade of this signaling pathway by the down-regulation of
      TGFbetaRII using SiRNA may provide a potential gene therapy for LAC.

PMID- 21725602
TI  - Genetic variability of the forkhead box O3 and prostate cancer risk in the
      European Prospective Investigation on Cancer.
AB  - Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor
      suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive
      oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3
      is a key downstream target of the PI3K-Akt pathway in response to cellular
      stimulation by growth factors or insulin and has been proposed as a bridge
      between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231,
      rs9400239 and rs479744) that have been shown to be strongly and consistently
      associated with longevity, were examined in relation to PC risk in a case control
      study of 1571 incident PC cases and 1840 controls nested within the European
      Prospective Investigation into Cancer and Nutrition (EPIC). There was no
      statistically significant association between the SNPs and PC risk regardless of
      the model of inheritance (dominant, codominant and recessive). The associations
      were not modified by disease aggressiveness, circulating levels of steroid sex
      hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that
      are associated with longevity are not major risk factors for PC risk, in this
      population of Caucasian men.

PMID- 21725603
TI  - Let-7d functions as novel regulator of epithelial-mesenchymal transition and
      chemoresistant property in oral cancer.
AB  - Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide. Let-7 family
      has been shown to function as a tumor suppressor through regulating multiple
      oncogenic signaling. Recent study reported that combined underexpression of miR
      205 and let-7d showed negative correlation with the survival prognosis of head
      and neck cancer patients. However, the let-7d-involved mechanism in regulating
      OSCC is still unclear. In this study, we first demonstrated that let-7d
      expression was significantly decreased while Twist and Snail expression was
      increased in OSCC cancer cell lines and primary cultures as compared to normal
      human oral keratinocyte cells. To further investigate the role of let-7d in OSCC,
      we applied the SPONGE method to knock down let-7d in OECM-1 and two primary OSCC
      cell types. The results showed that knockdown of let-7d promote epithelial
      mesenchymal transition (EMT) traits and migratory/invasive capabilities in OSCC
      cells. Furthermore, down-expression of let-7d significantly activated Twist and
      Snail expressions and chemo-resistant abilities of OSCC cells. Notably,
      overexpression of let-7d effectively reversed the EMT phenotype, blocked
      migratory/invasive abilities, and further increased the chemosensitivity in oral
      cancer tumor initiating ALDH1+ cells. In sum, these results show that let-7d
      negatively modulates EMT expression and also plays a role in regulating chemo
      resistant ability in oral cancer.

PMID- 21725604
TI  - Histone deacetylase 1 expression in gastric cancer.
AB  - The aim of this study was to identify and evaluate novel prognostic markers for
      gastric cancer. Differential mRNA displays comparing paired tumor/normal stomach
      samples were assessed. Several differentially expressed cDNA fragments of
      candidate genes were identified, and one of these was further studied using
      quantitative reverse transcription-PCR in 140 human gastric carcinomas. To
      evaluate protein expression, immunohistochemical staining was performed in
      selected cases. One of the genes abundantly expressed in tumor tissue on the
      differential mRNA displays was identified as histone deacetylase 1 (HDAC). HDAC
      was overexpressed in the tumor tissue in 77% of the cases as determined by
      quantitative reverse transcription-PCR. Immunohistochemical staining revealed
      analogous results, showing strong expression in cancer cells. Patients were then
      classified into high (n=78) and low (n=62) expression groups according to the
      mean value of HDAC expression. High frequencies of lymph vessel and vascular
      vessel permeations, and advanced stage of the disease were recognized in the high
      expression group compared to the low expression group (p<0.05). Prognosis was
      significantly worse for the high expression group than for the low expression
      group (p<0.05), and multi-variate analysis demonstrated that HDAC expression was
      an independent prognostic factor. Although not significantly different, lymph
      node metastasis was recognized more frequently in the high expression group
      (p=0.07). In conclusion, the findings show that HDAC expression is associated
      with aggressive behavior of primary gastric cancer, and imply that determination
      of the HDAC expression status is useful for predicting prognosis in patients with
      gastric cancer.

PMID- 21725605
TI  - Temozolomide decreases invasion of glioma stem cells by down-regulating TGF
      beta2.
AB  - Gliomas are characterized by excessive proliferation, diffuse infiltration and
      immunosuppression. Recent studies implicate a key role for a restricted
      population of glioma stem cells (GSCs) in glioma invasive growth and recurrence.
      Transforming growth factor (TGF)-beta2 is a mediator of immunosuppression
      associated with malignant glioma and also influences pro-invasive functions.
      Temozolomide (TMZ), is a new alkylating agent with promising antitumour efficacy
      for malignant gliomas, and the effect of TMZ on GSCs invasion has not been known.
      To address this issue, we developed studies aimed at neurospheres from primary
      cultured glioma cells, due to the fact that since neurospheres can be enriched in
      GSCs, we could examine whether TMZ inhibits the invasion of GSCs. TMZ reduced the
      TGF-beta2-mediated invasion, and down-regulated TGF-beta2 expression at the mRNA
      and protein levels. Thus, these results indicate that TMZ, as a chemotherapeutic
      agent, can reduce the invasion of GSCs and their immunosuppressive activity. TMZ
      may be used as an immunomodulating agent for glioma therapy.

PMID- 21725606
TI  - Induction of apoptosis by ethanol extract of Prunus mume in U937 human leukemia
      cells through activation of caspases.
AB  - Prunus mume (P. mume), a traditional drug and health food in Korea, Japan and
      China, possesses various pharmacological activities that include a potential
      source of free radical scavenging, anti-viral, anti-microbial, anti-inflammatory
      and anti-cancer activities. However, the cellular and molecular mechanisms of
      apoptosis induction by P. mume in human cancer cells are poorly understood. In
      the present study, we conducted an investigation of the pro-apoptotic effects of
      an ethanol extract of P. mume (EEPM) in U937 human leukemia cells. Exposure to
      EEPM was found to result in a concentration-dependent growth inhibition by
      induction of apoptosis. Induction of apoptotic cell death of U937 cells by EEPM
      showed a correlation with the down-regulation of members of the inhibitor of
      apoptosis protein (IAP) family, including X-linked inhibitor of apoptosis protein
      (XIAP) and survivin, and anti-apoptotic Bcl-2, up-regulation of FasL, and
      cleavage of Bic. EEPM treatment induced proteolytic activation of caspase-3, -8
      and -9, and degradation of caspase-3 substrate proteins, including poly(ADP
      ribose) polymerase (PARP) and beta-catenin. In addition, apoptotic cell death
      induced by EEPM was significantly inhibited by z-DEVD-fmk, a caspase-3-specific
      inhibitor, which demonstrated the important role played by caspase-3 in the
      process. Taken together, these findings suggest that EEPM may be a potential
      chemotherapeutic agent for use in the control of human leukemia U937 cells and
      that further studies are needed for the identification of the active compounds.

PMID- 21725607
TI  - Stephania delavayi Diels. inhibits breast carcinoma proliferation through the p38
      MAPK/NF-kappaB/COX-2 pathway.
AB  - The nuclear factor kappaB (NF-kappaB)/inhibitor of kappa kinase-beta (IKKbeta)
      signaling pathway is important in tumor promotion and progression. MDA-MB-231
      human breast carcinoma cells express COX-2 and show a constitutive
      phosphorylation of NF-kappaB. Many non-specific inhibitors of IKKbeta and NF
      kappaB are used to inhibit tumor promotion and progression. The Stephania
      delavayi Diels. (S. delavayi Diels.) extract has been reported to safely activate
      B cell immunity and there is evidence suggesting that it may be a promising new
      anticancer therapeutic agent. S. delavayi Diels. extract suppressed proliferation
      of the breast cancer cell lines MDA-MB-231 and MCF-7 by inducing cell death. To
      aid in the development of the S. delavayi Diels. extract as a therapeutic agent,
      its mechanisms of action were investigated, in particular its effects on p38
      MAPK, NF-kappaB and COX-2, which play important roles in inflammation and cancer.
      S. delavayi Diels. stimulated p38 MAPK phosphorylation but reduced NF-kappaB
      phosphorylation and COX-2 expression in a dose- and time-dependent manner. Thus,
      S. delavayi Diels., which appears to act primarily through p38 MAPK/NF-kappaB/COX
      2 signaling in breast carcinomas, may be a potent anticancer agent with target
      specificity and low toxicity.

PMID- 21725608
TI  - Decreased expression of profilin 2 in oral squamous cell carcinoma and its
      clinicopathological implications.
AB  - Profilins are small proteins essential for many normal cellular dynamics and
      constitute one of the crucial components of actin-based cellular motility.
      Several recent studies have implicated a role for the profilin (PFN) family in
      cancer pathogenesis and progression. However, their expression and promising
      functions are largely unknown in oral squamous cell carcinoma (OSCC). In this
      study, we analyzed the correlation between PFN1 and PFN2 expression in vitro and
      in vivo. The protein expression levels were roughly compared between cell lines
      (HIOEC, HB96) with the employment of mass spectrometry. PFN2 was singled out as
      one of the significantly down-regulated genes in the cancerous HB96 cells. The
      expression levels of PFN1 and PFN2 in vitro were validated by RT-PCR, real-time
      PCR and Western blotting. Laser scanning confocal microscopy was used for the
      first time to assess the localization of PFN2 expression. In subsequent
      experiments, we observed the relationship between PFN2 expression levels and the
      proliferation of transfected HB96 cancer cells. VASP, N-WASP and P27 expression
      was also examined in the PFN2-transfected or non-transfected HB96 cells. In vivo,
      antigen expression was determined by immunohistochemical analyses in 88 paired
      tissue specimens. Decreased protein expression was confirmed in cancerous tissues
      from 88 OSCC patients compared with paracancerous normal mucous epithelia. Tumors
      with weak PFN2 expression were associated with a significantly worse prognosis
      than strongly expressed tumours (P<0.001). Other statistical analyses were
      performed to assess the differences in expression and their clinical and
      pathological significance. In conclusion, PFN2 can be utilized as both a
      potential suppressor marker and a prognostic protein for OSCC. The function of
      PFN2 may be to regulate the N-WASP/Arp2/3 signaling pathway.

PMID- 21725609
TI  - PRL-3 promotes the proliferation of LoVo cells via the upregulation of KCNN4
      channels.
AB  - Previous studies have shown that phosphatase of regenerating liver-3 (PRL-3)
      plays an important role in the metastasis and proliferation of tumor cells.
      However, the mechanism by which PRL-3 controls the cell cycle of tumor cells
      remains unknown. In the present study, considering that the K+ channels strictly
      control cell proliferation, we examined whether K+ channels participate in the
      proliferation of tumor cells induced by PRL-3. Interestingly, the expression of
      intermediate-conductance Ca2+-activated K+ channels (KCNN4) was upregulated in an
      NF-kappaB-dependent manner when PRL-3 was transfected into LoVo cells. Also, we
      identified two NF-kappaB binding sites in the promoter region of KCNN4. Use of
      the specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34)
      significantly inhibited the proliferation induced by PRL-3 and blocked the cell
      cycle at the G2/M phase. Meanwhile, the level of phosphorylation of Cdc2 was
      increased in a dose-dependent manner. Furthermore, TRAM-34 also inhibited tumor
      formation of PRL-3 cell xenografts implanted by injection in nude mice. In
      conclusion, PRL-3 promoted the proliferation of LoVo cells through upregulation
      of KCNN4 channels which facilitated the G2/M transition.

PMID- 21725610
TI  - Induction of apoptosis by casticin in cervical cancer cells through reactive
      oxygen species-mediated mitochondrial signaling pathways.
AB  - Casticin, one of the main components from Fructus Viticis, has been reported to
      inhibit the growth of various cancer cells, including the human cervical cancer
      cell line HeLa. The purpose of this study was to examine the apoptotic activity
      and molecular mechanism of casticin action on human cervical cancer cells. The
      apoptotic activity of casticin on human cervical cancer HeLa, CasKi, SiHa and
      peripheral blood mononuclear cells (PBMCs) was measured using a histone/DNA ELISA
      assay, flow cytometry with propidium iodide (PI) staining and DNA agarose gel
      electrophoresis. The mitochondrial membrane potential and reactive oxygen species
      (ROS) production were evaluated by flow cytometry analysis. Caspase activities
      were assayed using a caspase colorimetric activity assay kit. Protein expression
      levels of cytochrome c, Bax, Bcl-2, Bcl-xL and XIAP were analyzed by Western
      blotting. Casticin caused accumulation of the Sub-G1 cells and increased reactive
      oxygen species (ROS) production in HeLa, CasKi, SiHa cell lines, but not in
      PBMCs. Apoptosis of HeLa cells was induced by casticin via mitochondrial release
      of cytochrome c due to the reduction of mitochondrial trans-membrane potential,
      activation of caspase-3 and -9, and the production of reactive oxygen species.
      The pan caspase inhibitor zVAD-FMK, the caspase-9 inhibitor zLEHD-fmk and N
      acetylcysteine suppressed casticin-induced apoptosis. Bax was upregulated, while
      expression levels of Bcl-xL and XIAP were downregulated. However, there was no
      change in the expression of Bcl-2 under the same treatment. Our results indicate
      that casticin-induced apoptosis of cervical cancer cells is mediated by ROS
      generation and mitochondrial signaling pathways.

PMID- 21725611
TI  - RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK
      activation.
AB  - Accumulating studies have shown that the receptor activator of nuclear factor
      kappaB ligand (RANKL)/RANK pathway plays an important role in tumor metastasis.
      However, the involvement of the RANKL/RANK signal transduction pathway in breast
      cancer metastasis remains unclear. The present study, therefore, investigated the
      role of downstream molecules of RANKL/RANK signaling in breast cancer cells using
      Transwell chemotaxis assays. RANKL was shown to direct the migration of MDA-MB
      231 breast cancer cells. Osteoprotegerin (OPG; soluble decoy receptor of RANKL)
      inhibited RANKL-induced migration. RANKL activated Src kinase in MDA-MB-231
      cells, as shown by Western blotting, and pretreatment with a Src inhibitor
      abrogated RANKL-induced cell migration, in a similar manner to OPG. Short-hairpin
      RNA against RANK, delivered via a lentiviral vector, significantly abolished the
      expression of phosphorylated Src. Stimulation by RANKL induced the
      phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK, p38, JNK), and
      specific inhibitors of MAPKs blocked RANKL-induced cell migration. Furthermore,
      the expression of phosphorylated MAPKs could be blocked by a Src inhibitor and by
      small interfering RNA against Src. These findings suggest that Src and MAPK
      pathways may be involved in RANKL-induced MDA-MB-231 breast cancer cell
      migration.

PMID- 21725612
TI  - SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells.
AB  - Mammary serine protease inhibitor B5 (SerpinB5) is a potential oncogene in
      gastric cancer (GC); however, the molecular mechanism by which SerpinB5 promotes
      oncogenesis remains elusive. In this study, SerpinB5-associated proteins were
      selected based on yeast two-hybrid screening and microarray analysis after RNA
      interference and were validated using co-immunoprecipitation (Co-IP) and RNA Co
      IP. The expression profiles of the interacting proteins were analyzed by Western
      blotting and immunohistochemistry. The effects of SerpinB5 on KHDRBS3 and FBXO32
      expression in GC cells were analyzed using real-time PCR and Western blotting
      after the expression of SerpinB5 was modified. By yeast two-hybrid screening and
      microarray analysis, FBXO32 and KHDRBS3 were found to be SerpinB5-interacting
      proteins. The interactions were confirmed by Co-IP. An RNA co-immunoprecipitation
      assay found that KHDRBS3 interacted with FBXO32 mRNA. The expression of SerpinB5
      was much stronger in the nucleus of GC cells. FBXO32 was expressed at higher
      levels in the cytoplasm of GC cells. KHDRBS3 was primarily detected in the
      nucleus of normal mucosal cells. SerpinB5 expression was modified in GC cells,
      KHDRBS3 mRNA levels remained stable, however, FBXO32 mRNA levels changed 24 h
      after changes in KHDRBS3 protein levels were detected. In conclusion, SerpinB5
      interacts with KHDRBS3 and FBXO32, and KHDRBS3 can interact with FBXO32 mRNA.

PMID- 21725613
TI  - Growth inhibition by NVP-BEZ235, a dual PI3K/mTOR inhibitor, in hepatocellular
      carcinoma cell lines.
AB  - Dysregulation of the phosphatidylinositol-3-kinase (PI3K)/mammalian target of
      rapamycin (mTOR) pathway frequently occurs in human tumors, and is therefore
      considered to be a good molecular target for treatment. In hepatocellular
      carcinoma (HCC), overexpression of p-Akt and decrease of PTEN expression have
      been reported. NVP-BEZ235 is a novel dual inhibitor of PI3K and mTOR; however,
      its effect on HCC has not been documented. Consequently, we investigated the
      effects of NVP-BEZ235 on the PLC/PRF/5, HLE, JHH7 and HepG2 HCC cell lines in
      vitro and in vivo. NVP-BEZ235 decreased the levels of p-Akt and p-p70S6K and
      inhibited cell proliferation in all HCC cell lines in a dose-dependent manner.
      Flow cytometric analysis revealed that inhibition of cell proliferation by NVP
      BEZ235 was accompanied by G1 arrest in all cell lines, and that NVP-BEZ235
      induced apoptosis in PLC/PRF/5 and HLE cells. Tumor growth was suppressed without
      body weight loss when NVP-BEZ235 was orally administered to JHH-7 tumor-bearing
      mice for 11 days. These results suggest that NVP-BEZ235 is a potential new
      candidate for targeted HCC therapy.

PMID- 21725614
TI  - Advanced two-step transcriptional amplification as a novel method for cancer
      specific gene expression and imaging.
AB  - The two-step transcriptional amplification (TSTA) system was previously reported
      to enhance the tissue-specific gene expression driven by weak promoters, but the
      enhancement of the gene expression is limited to use in in vitro and in vivo
      experimental situations. To achieve robust tissue-specific gene expression using
      the TSTA system, we developed an advanced TSTA system which includes
      polyglutamines and rat glucocorticoid receptor sequences between the GAL4 and
      VP16 sequences in the region of the first step of transcription. We evaluated the
      advanced TSTA system as a method to enhance the human telomerase reverse
      transcriptase (hTERT) promoter-driving cancer-specific transcription in various
      cancer cell lines. As a result, the advanced TSTA enhanced cancer-specific
      luciferase gene expression in all of the examined cancer cell lines, when
      compared with both the one-step and conventional TSTA systems (an ~6- and ~17
      fold enhancement, respectively). Notably, the enhancement of the hTERT driven
      expression by the conventional TSTA system was modest and even inferior to the
      one-step system in several cancer cell lines. We then constructed a luciferase
      gene encoding the adeno-associated virus vector in which the hTERT promoter
      mediated expression was driven by the advanced TSTA or control systems. In an
      orthotopic liver tumor model, mice were treated with the vector via tail vein
      injection. An optical imaging device was used to visualize the in vivo luciferase
      expression in the orthotopic tumor. The advanced TSTA system significantly
      enhanced the luciferase expression compared with the one-step and conventional
      TSTA systems (18.0+/-1.0- and 15.9+/-0.85-fold gain, respectively). Therefore,
      the advanced TSTA system significantly improves hTERT-dependent cancer-specific
      gene expression both in vitro and in vivo when compared with the previous
      systems. Since the advanced TSTA method can also be applied to other site
      specific gene expression systems using tissue-specific promoters, this approach
      is expected to become a valuable tool enabling in vivo site-specific targeting in
      the field of gene therapy and molecular imaging.

PMID- 21725615
TI  - microRNA expression profiling of endometrial endometrioid adenocarcinomas and
      serous adenocarcinomas reveals profiles containing shared, unique and
      differentiating groups of microRNAs.
AB  - microRNAs (miRNAs) control a multitude of pathways in human cancers. Differential
      expression of miRNAs among different histological types of tumors within the same
      type of tissue offers insight into the mechanism of pathogenesis and may help to
      direct treatment to improve prognosis. We assessed expression of 667 miRNAs in
      endometrial endometrioid and serous adenocarcinomas using RNA extracted from
      benign endometrium as well as from primary endometrial tumors. Quantitative miRNA
      profiling of endometrial adenocarcinomas revealed four overlapping groups of
      significantly overexpressed and underexpressed miRNAs. The first group was
      composed of 20 miRNAs significantly dysregulated in both adenocarcinoma types
      compared with benign endometrium, two groups were composed of miRNAs
      significantly dysregulated in either endometrioid adenocarcinomas or in serous
      adenocarcinomas compared with benign endometrium, and the fourth group was
      composed of 17 miRNAs that significantly distinguished between endometrioid
      adenocarcinomas and serous adenocarcinomas themselves. Validation of the
      expression levels of the selected miRNAs was carried out in a second panel
      composed of ten endometrioid and five serous tumors. Experimentally validated
      mRNA targets of these dysregulated miRNAs were identified using published
      sources, whereas TargetScan was used to predict targets of miRNAs in the first
      and fourth profile groups. These validated and potential miRNA target lists were
      filtered using published lists of genes displaying significant overexpression or
      underexpression in endometrial cancers compared to benign endometrium. Our
      results revealed a number of dysregulated miRNAs that are commonly found in
      endometrial (and other) cancers as well as several dysregulated miRNAs not
      previously identified in endometrial cancers. Understanding these differences may
      permit the development of both prognostic and diagnostic biomarkers.

PMID- 21725616
TI  - Cilengitide inhibits metastatic bone colonization in a nude rat model.
AB  - Integrins alphavbeta3 and alphavbeta5 are considered to play an important role in
      the pathogenesis of breast cancer bone metastases. This study investigates the
      effects of the alphavbeta3/alphavbeta5 integrin-specific inhibitor cilengitide
      during early metastatic bone colonization. The impact of cilengitide on the
      migration, invasion and proliferation of MDA-MB-231 human breast carcinoma cells
      as well as on bone resorption by osteoclasts was investigated in vitro. For in
      vivo experiments, nude rats were treated with cilengitide for 30 days starting
      one day after site-specific tumor cell inoculation in the hind leg, and the
      course of metastatic changes in bone was followed using flat-panel volumetric
      computed tomography (VCT) and magnetic resonance imaging (MRI). Vascular changes
      in bone metastases were investigated using dynamic contrast-enhanced (DCE-) MRI
      derived parameters amplitude A and exchange rate coefficient kep. In vitro,
      cilengitide treatment resulted in a decrease in proliferation, migration and
      invasion of MDA-MB-231 cells, as well as of osteoclast activity. In vivo, the
      development of bone metastasis in the hind leg of rats was not prevented by
      adjuvant cilengitide treatment, but cilengitide reduced the volumes of osteolytic
      lesions and respective soft tissue tumors of developing bone metastases as
      assessed with VCT and MRI, respectively. DCE-MRI revealed significant changes in
      the A and kep parameters including decreased relative blood volume and increased
      vessel permeability after cilengitide treatment indicating vessel remodeling. In
      conclusion, during early pathogenic processes of bone colonization, cilengitide
      treatment exerted effects on tumor cells, osteoclasts and vasculature reducing
      the skeletal lesion size of experimental skeletal metastases.

PMID- 21725617
TI  - Overexpression of SALL4 in lung cancer and its importance in cell proliferation.
AB  - Few target molecules have been identified that enable the diagnosis of lung
      cancer with high sensitivity and specificity, especially in the early clinical
      stages. Herein, we present the first evidence for mRNA overexpression of SALL4, a
      transcription factor essential for embryonic development and the self-renewal of
      embryonic stem cells, in lung cancer. Analysis using cancerous and noncancerous
      tissues revealed that the sensitivity and specificity of SALL4 mRNA were 85.1 and
      92.9%, respectively, estimated using the cutoff value obtained from analyzing the
      receiver operating characteristic curve. Furthermore, comparison of paired
      tissues from the same patient revealed elevated SALL4 mRNA levels that were
      greater than two-fold in 93% of the specimens. SALL4 mRNA was highly expressed
      even in the early clinical stages and there was no difference in the positivity
      rate between stage IA and other stages. An siRNA approach to determine the
      significance of SALL4 expression revealed catastrophic growth inhibition of SBC-1
      lung cancer cells that was induced by cell cycle arrest at the G1/early S phase.
      Therefore, SALL4 mRNA may be a candidate for use as support in the diagnosis of
      lung cancer, and may also represent a therapeutic target.

PMID- 21725618
TI  - miR-122 inhibits viral replication and cell proliferation in hepatitis B virus
      related hepatocellular carcinoma and targets NDRG3.
AB  - microRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional
      regulatory functions that participate in diverse biological pathways. miR-122, a
      liver-specific miRNA, has been found to be down-regulated in hepatocellular
      carcinoma (HCC) and HCC-derived cell lines. In this study, miR-122 was down
      regulated in the hepatitis B virus (HBV)-related HCC cell line HepG2.2.15
      compared to HepG2. NDRG3, a member of the N-myc downstream-regulated gene (NDRG)
      family, was up-regulated in HepG2.2.15 and was identified as a target gene of miR
      122. An inverse correlation between the expression of miR-122 and the NDRG3
      protein was noted in HBV-related HCC specimens. The transfection of the miR-122
      expression vector into the HepG2.2.15 cell line repressed the transcription and
      expression of NDRG3, which subsequently reversed the malignant phenotype of the
      cells. The replication of HBV, expression of viral antigens and proliferation of
      cells were significantly inhibited by restoration of miR-122. The data
      demonstrate that miR-122 plays an important role in HBV-related
      hepatocarcinogenesis by targeting NDRG3. Thus, miR-122 and NDRG3 represent key
      diagnostic markers and potential therapeutic targets for HBV-related HCC.

PMID- 21725619
TI  - TCF3 inhibits F9 embryonal carcinoma growth by the down-regulation of Oct4.
AB  - T-cell factor 3 (TCF3), a downstream effector of Wnt signaling in embryonic stem
      (ES) cells, plays an important role in pluripotent self-renewal and
      proliferation. Loss of TCF3 delays the differentiation of mouse ES cells. The
      purpose of this study was to investigate the effect of TCF3 on embryonal
      carcinoma (EC). The mouse F9 EC cell line and a tumor-bearing mouse model were
      used to evaluate the anti-EC tumor effects of TCF3 in vitro and in vivo,
      respectively. The overexpression of TCF3 significantly inhibited proliferation,
      colony-forming and migration in F9 EC cells by approximately 30, 45 and 30%,
      respectively. The in vivo mouse model showed that the overexpression of TCF3
      significantly reduced tumor volume (36.4%) and tumor weight (34.8%), malignancy
      progression and local infiltration and prolonged the life span of tumor-bearing
      mice. Overexpression of TCF3 significantly down-regulated Oct4 expression in the
      F9 EC cells. The results indicate that TCF3 is an inhibitor of the malignant
      phenotypes of embryonal carcinoma through the regulation of Oct4 expression.

PMID- 21725620
TI  - Computer-aided detection scheme for sentinel lymph nodes in lymphoscintigrams
      using symmetrical property around mapped injection point.
AB  - It is difficult to detect sentinel lymph nodes (SLNs) around an injection point
      of radiopharmaceuticals mapped in lymphoscintigrams. The purpose of this study
      was to develop a computer-aided detection (CAD) scheme for SLNs by a subtraction
      technique using the symmetrical property in the mapped injection point. Our
      database consisted of 78 lymphoscintigrams with 86 SLNs. In our CAD scheme, the
      mapped injection point of radiopharmaceuticals was first segmented from the
      lymphoscintigram using a gray-level thresholding technique. Lymphoscintigram was
      then divided into four regions by vertical and horizontal straight lines through
      the center of the segmented injection point. One of the four divided regions was
      defined as the target region. The correlation coefficients based on pixel values
      were calculated between the target region and each of the other three regions.
      The region with the highest correlation coefficient among three regions was
      selected as the similar region to the target region. The values of pixels on the
      target region were subtracted by the values of the corresponding pixels on the
      similar region. This procedure was repeated until every divided region had been
      used as target region. SLNs were segmented by applying a gray-level thresholding
      technique to the subtracted image. With our CAD scheme, sensitivity and the
      number of false positives were 95.3% (82/86) and 2.51 per image, respectively.
      Our CAD scheme achieved a high level of detection accuracy, and would have a
      great potential in assisting physicians to detect SLNs in lymphoscintigrams.

PMID- 21725621
TI  - Optimization of the radiological protection of patients undergoing digital
      radiography.
AB  - Because of a much higher dynamic range of flat panel detectors, patient dose can
      vary without change of image quality being perceived by radiologists. This
      condition makes optimization (OT) of radiation protection undergoing digital
      radiography (DR) more complex, while a chance to reduced patient dose also
      exists. In this study, we evaluated the difference of patient radiation and image
      rejection before and after OT to identify if it is necessary to carry out an OT
      procedure in a routine task with DR. The study consisted of a measurement of the
      dose area product (DAP) and entrance surface dose (ESD) received by a reference
      group of patients for eight common radiographic procedures using the DR system
      before and after OT. Meanwhile image rejection data during two 2-month periods
      were collected and sorted according to reason. For every radiographic procedure,
      t tests showed significant difference in average ESD and DAP before and after OT
      (p < 0.005). The ESDs from most examinations before OT were three times higher
      than that after OT. For DAPs, the difference is more significant. Image rejection
      rate after OT is significantly lower than that before OT (chi (2) = 36.5, p <
      0.005). The substantial reductions of dose after OT resulted from appropriate mAs
      and exposure field. For DR patient dose, less than recommended diagnostic
      reference level can meet quality criteria and clinic diagnosis.

PMID- 21725622
TI  - Identification of apical vertebra for grading of idiopathic scoliosis using image
      processing.
AB  - Scoliosis is a 3-D deformity of spinal column, characterized by both lateral
      curvature and vertebral rotation. The disease can be caused by congenital,
      developmental, or degenerative problems; but most cases of scoliosis actually
      have no known cause, and this is known as idiopathic scoliosis. Vertebral
      rotation has become increasingly prominent in the study of scoliosis and the most
      deformed vertebra is named as apical vertebra. Apical vertebral deformity
      demonstrates significance in both preoperative and postoperative assessment,
      providing better appreciation of the impact of bracing or surgical interventions.
      Precise measurement of apical vertebral rotation in terms of grading is most
      valuable for the determination of reference value in normal and pathological
      conditions for better understanding of scoliosis. Routine quantitative evaluation
      of vertebral rotation is difficult and error prone due to limitations of observer
      characteristic and specific imaging property. This paper proposes automatic
      identification of the apical vertebra and its parameter that depends on the
      objective criteria of measurement using active contour models. The proposed
      technique is more accurate and is a reliable measurement compared to manual and
      computer-assisted system.

PMID- 21725623
TI  - IL-10 modulates fondaparinux inhibition of monocyte-induced thrombin generation.
AB  - In addition to its established immuno-regulating capacity, the anti-inflammatory
      cytokine interleukin (IL)-10 exerts direct effects on coagulation. IL-10 down
      regulates the expression of tissue factor (TF) and thrombin generation (TG).
      Thus, we hypothesised that IL-10 could enhance the effect of anticoagulants. To
      evaluate in vitro the potential additive effect of IL-10 on fondaparinux-induced
      anticoagulation. Human monocytes were purified by elutriation, and were activated
      by factor Xa (FXa). Real-time RT-PCR and Western blotting were used to evaluate
      FXa-induced TF synthesis. TG test was used as a functional test to assess TF
      dependent monocyte procoagulation, and to evaluate the effects of IL-10 (200 and
      500 pg/ml) and fondaparinux (0.0, 0.1, 0.4, 0.7 and 1.2 MUg/ml), separately and
      in combination. We confirmed that FXa induced TF mRNA and protein synthesis by
      monocyte in a concentration dependent manner. We showed that FXa-activated
      monocytes triggered TG via TF expression. We reported that IL-10 inhibited TG
      with a marginal effect seen at 200 pg/ml. Results with fondaparinux showed a
      concentration-dependent TG inhibition. The combination of IL-10 and fondaparinux
      effects demonstrated that IL-10: (i) potentiates the inhibitory effect of
      fondaparinux on TG by 10-30%, and (ii) dramatically modifies fondaparinux IC50
      for each TG parameter. IL-10 enhances in vitro the extent of anticoagulation
      induced by fondaparinux.

PMID- 21725624
TI  - Acculturation and health care utilization among Mexican heritage women in the
      United States.
AB  - With the increasing Latino population in the United States, it is critical to
      examine the influence of the process of acculturation on health care practices
      and utilization. The purpose of this study was to evaluate the relationship
      between acculturation level and post-partum visit (PPV) compliance among Latinas
      participating in a larger psycho-educational intervention aimed at encouraging
      women to engage in positive healthcare practices. Acculturation was measured with
      the Bicultural Involvement Questionnaire which assigned participants to five
      categories: Assimilated, Separated, Moderate, Bicultural and Alienation. Logistic
      Regression analyses were conducted to predict post-partum visit attendance. Odds
      ratios and relative risk of not attending the post-partum visit are presented.
      Results suggest women in the Separation and Assimilation groups were less likely
      than bicultural group members to attend the PPV. The only other variable that was
      significant in this analysis is the group condition, indicating that the
      intervention group was more likely to attend the PPV than the control group.
      Women identifying as bicultural seem to participate more actively in their own
      healthcare as they draw on the cultural assets that have a positive influence on
      informal health practices, such as healthy eating and refraining from drug use.
      Bicultural group members can also use formal skills related to language and
      knowledge of the dominant culture to help effectively navigate the healthcare
      system. Implications for research, intervention and practice are discussed to
      improve healthcare practices and increase utilization among Latinas.

PMID- 21725625
TI  - Assessment of the metal bioaccumulation in three species of freshwater bivalves.
AB  - The metal concentration and body burden of three species of fresh water bivalves,
      Parreysia cylindrica, Parreysia corrugata and Corbicula striatella were estimated
      in laboratory experiment after exposure to chronic concentration of arsenic
      (0.1719 ppm), cadmium (0.23 ppm), copper (0.13 ppm), mercury (0.06 ppm), lead
      (2.4 ppm) and zinc (5.1 ppm) separately up to 30 days. Dry weight of each animal
      was used to calculate metal concentrations (MUg/g) and the metal body burden
      (MUg/individual). It was observed that zinc, lead and copper concentration and
      metal body burden was highest in the Corbicula striatella, mercury and arsenic
      was highest in Parreysia corrugata and cadmium was highest in Parreysia
      cylindrica. Therefore, Corbicula striatella is being proposed as sentinel
      organism for monitoring of zinc, lead and copper, Parreysia corrugata for mercury
      and arsenic, and Parreysia cylindrica for cadmium in fresh water ecosystem.

PMID- 21725626
TI  - Lead poisoning among Arab American and African American children in the Detroit
      metropolitan area, Michigan.
AB  - This study explored the hypothesis that acculturation is a risk factor for
      childhood lead poisoning in the Detroit area of Michigan. Blood lead levels
      (BLLs) were determined in 429 Arab American and African American children, aged 6
      months to 15 years, who were receiving well-child examination in three Women,
      Infant, and Children (WIC) clinics in the city. Mean BLL was 3.8 +/- 2.3 MUg/dL
      (range: 1-18 MUg/dL) and 3.3% of the children tested had blood lead values above
      the 10 MUg/dL level of concern. Neither the age of the dwelling units nor
      ethnicity of the child was significantly associated with the BLL. Multivariable
      analyses instead identified a number of acculturation-related factors that are
      associated with elevation in blood lead including paternal education, language
      spoken at home (English only, English and Arabic, or Arabic only), home
      ownership, smoking in the home, and exposure of child to home health remedies.
      The difference in blood lead between Arab American children from families where
      Arabic only versus Arabic and English is spoken at home was found to be
      statistically significant. This study provides information showing that immigrant
      children are at heightened risk of being poisoned by lead which can be useful in
      identifying groups at risk of atypical exposures.

PMID- 21725627
TI  - Health behaviors of early-stage non-small cell lung cancer survivors.
AB  - INTRODUCTION: Lung cancer survivors are at risk for cancer recurrence and other
      chronic illnesses related predominantly to prior tobacco use and older age.
      Optimal quality of post-treatment care requires greater knowledge of survivors'
      adherence to behavioral health recommendations. This study reports the rates of
      smoking, physical activity, alcohol use, cancer screenings, and routine primary
      care visits in non-small cell lung cancer (NSCLC) survivors. METHODS: Stage IA
      and IB NSCLC survivors (N = 183, mean age = 69.0 years) with no evidence of
      disease 1-6 years post-treatment completed standard survey items regarding health
      and cancer screening behaviors. RESULTS: Most survivors (83.5%) had a history of
      smoking, but 64.8% quit prior to diagnosis and only 5.5% continued to smoke.
      Alcohol intake recommendations were exceeded by 5.4% and 17.3% of men and women,
      respectively. In a typical week, 23.1% met physical activity guidelines.
      Regarding cancer screenings, 89.3% were adherent to colorectal cancer screening
      guidelines. Among women, 72.0% had a mammogram within the previous year and 81.5%
      had a pap test in the previous 3 years; among men, 86.7% had a prostate-specific
      antigen test in the previous year. Almost all (97.3%) had seen a primary care
      provider in the past year. DISCUSSIONS/CONCLUSIONS: The majority of lung cancer
      survivors were adherent to health promotion recommendations, but few engaged in
      the recommended level of physical activity. IMPLICATIONS FOR CANCER SURVIVORS:
      Physical and pulmonary rehabilitation interventions may help lung cancer
      survivors maintain sufficient levels of physical activity, which can have
      numerous benefits for older adults.

PMID- 21725628
TI  - Impact of multi-approach strategy on acid suppressive medication use in a
      teaching hospital in Qatar.
AB  - OBJECTIVE: To evaluate the impact of a multi-approach strategy to improve the
      appropriate usage of acid suppressive medication (ASM) in medical inpatients and
      compare it with the baseline data from 2007. SETTING: Five general medicine wards
      in a 600-bed teaching hospital in Doha, Qatar. METHOD: A prospective evaluation
      of the usage of ASM 1 year after a multi-approach strategy. This consisted of
      four main interventions: audit and feedback method (including awareness lectures
      to all medical and pharmacy staff), implementation of a usage guideline for
      medical inpatients, circulating a logarithmic chart on the proper usage of ASM
      for medical inpatients from admission through to discharge and participation of
      clinical pharmacists in the multidisciplinary rounds. All medical patients
      admitted from May through June 2009 were evaluated. Data about the usage of ASM
      were collected upon and during admission, at discharge and at the next follow-up
      visit. Justified indications for its usage were based on the approved product
      information and on evidence-based literature recommendations. Data were compared
      with the findings of the baseline clinical audit done 2 years earlier. MAIN
      OUTCOME MEASURE: The usage of ASM in justified and non-justified indications upon
      and during admission, at discharge and at the next follow up visit. RESULTS: A
      total of 414 patients were admitted during the study period, 208 patients (50%)
      received ASM compared to 53% in 2007 (206 patients out of 389). Seventy-four
      patients (36%) were using ASM upon admission compared to 48 patients (23%) in the
      2007 clinical audit. Inappropriate ASM use decreased with 51% during admission
      (66 to 32%, P < 0.0001), 62% at discharge (34 to 13%, P < 0.0001) and 67% at the
      next follow up visit (15 to 5%, P = 0.0008). CONCLUSION: Despite the higher
      number of patients receiving ASM upon admission, the multi-approach strategy used
      in our institution resulted in a significant improvement in the appropriate usage
      of ASM in medical inpatients.

PMID- 21725629
TI  - High-fat diets affect energy and bone metabolism in growing rats.
AB  - BACKGROUND: High-fat diets are usually associated with greater weight (W) gain
      and body fat (BF). However, it is still unclear whether the type and amount of
      fat consumed influence BF. Additionally, dietary fat intake may also have
      consequences on skeletal health. OBJECTIVE: To evaluate in healthy growing rats
      the effects of high-fat diets and type of dietary fat intake (saturated or
      vegetable oils) on energy and bone metabolism. METHODS: At weaning, male Wistar
      rats (n = 50) were fed either a control diet (C; fat = 7% w/w) or a high-fat diet
      (20% w/w) containing either: soybean oil, corn oil (CO), linseed oil (LO), or
      beef tallow (BT) for 8 weeks. Zoometric parameters, BF, food intake and
      digestibility, and total and bone alkaline phosphatase (b-AP) were assessed.
      Total skeleton bone mineral density (BMD) and content (BMC), BMC/W, spine BMD,
      and bone volume (static-histomorphometry) were measured. RESULTS: Animals fed BT
      diet achieved lower W versus C. Rats fed high-fat vegetable oil diets showed
      similar effects on the zoometric parameters but differed in BF. BT showed the
      lowest lipid digestibility and BMC. In contrast, high vegetable oil diets
      produced no significant differences in BMC, BMC/W, BMD, spine BMD, and bone
      volume. Marked differences were observed for LO and BT groups in b-AP and CO and
      BT groups in bone volume. CONCLUSION: BT diet rich in saturated fatty acids had
      decreased digestibility and adversely affected energy and bone metabolisms, in
      growing healthy male rats. There were no changes in zoometric and bone parameters
      among rats fed high vegetable oil diets.

PMID- 21725630
TI  - Double-phase (131)I whole body scan and (131)I SPECT-CT images in patients with
      differentiated thyroid cancer: their effectiveness for accurate identification.
AB  - OBJECTIVE: This study aims to determine whether a (131)I double-phase whole body
      scan (WBS) and SPECT-CT images have added value over a single-phase WBS image in
      identifying benign and malignant lesions in patients with well-differentiated
      thyroid cancer (DTC) at their first radioactive iodine (RAI) treatment. METHODS:
      This study included 42 DTC patients who underwent their first radioablation. Post
      therapeutic WBS images were acquired after 3 days (early phase) and 7 days
      (delayed phase). Following early-phase WBS, SPECT-CT images were obtained. The
      images were reviewed independently of the clinical data by 2 board-certified
      observers with a 6-point scoring system (benign to malignant -3 to +3). RESULTS:
      The double-phase WBS and SPECT-CT images showed 115 radioiodine-avid
      localizations (81 benign and 34 malignant accumulations). Confidence levels of
      benign accumulations were significantly higher with SPECT-CT (average score -2.40
      +/- 1.06) compared to those of the early-phase WBS (average score -1.39 +/- 1.88)
      (p < 0.0001) and delayed-phase WBS images (average score -1.49 +/- 1.19) (p <
      0.0001). When the analysis was restricted to accumulations with a low confidence
      score in the early-phase WBS image, the confidence level of the delayed-phase WBS
      was higher compared to that of the early-phase WBS images (p = 0.0012). The
      confidence levels of malignant accumulations were significantly higher with SPECT
      CT images (average score 2.37 +/- 0.96) compared to the early-phase WBS (average
      score 1.44 +/- 1.21) (p < 0.0001) and the delayed-phase WBS images (average score
      1.50 +/- 1.13) (p < 0.0001). CONCLUSION: Post-therapeutic SPECT-CT image was
      superior to the early-phase WBS image in enhancing the confidence level and
      accurately localizing the lesions. The delayed-phase WBS image contributed to the
      accurate diagnosis of benign lesions with a low confidence level in the early
      phase WBS image.

PMID- 21725631
TI  - Shotgun proteomic analytical approach for studying proteins adsorbed onto
      liposome surface.
AB  - The knowledge about the interaction between plasma proteins and nanocarriers
      employed for in vivo delivery is fundamental to understand their biodistribution.
      Protein adsorption onto nanoparticle surface (protein corona) is strongly
      affected by vector surface characteristics. In general, the primary interaction
      is thought to be electrostatic, thus surface charge of carrier is supposed to
      play a central role in protein adsorption. Because protein corona composition can
      be critical in modifying the interactive surface that is recognized by cells,
      characterizing its formation onto lipid particles may serve as a fundamental
      predictive model for the in vivo efficiency of a lipidic vector. In the present
      work, protein coronas adsorbed onto three differently charged cationic liposome
      formulations were compared by a shotgun proteomic approach based on nano-liquid
      chromatography-high-resolution mass spectrometry. About 130 proteins were
      identified in each corona, with only small differences between the different
      cationic liposome formulations. However, this study could be useful for the
      future controlled design of colloidal drug carriers and possibly in the
      controlled creation of biocompatible surfaces of other devices that come into
      contact with proteins into body fluids.

PMID- 21725632
TI  - C-reactive protein (CRP) aptamer binds to monomeric but not pentameric form of
      CRP.
AB  - Native C-reactive protein (CRP) is composed of five identical subunits arranged
      in a pentameric structure (pCRP). Binding of pCRP to damaged cell membranes
      produces a second isoform, modified CRP, which has similar antigenicity to
      isolated monomeric subunits of CRP (mCRP). Emerging evidence indicates that
      modified CRP plays a role in inflammation and atherosclerosis, however, there are
      very few techniques that can distinguish the different isoforms of CRP. Here we
      show that an RNA aptamer binds specifically to mCRP and not to pCRP. Using this
      aptamer, we describe a simple, fast, and sensitive assay to detect nanomolar
      concentrations of mCRP using fluorescence anisotropy. In addition, we show that
      this aptamer can be used to detect mCRP in polyacrylamide gels and bound to a
      surface using total internal reflection fluorescence microscopy. The biological
      activity of the mCRP we prepared by heating pCRP with 0.1% sodium dodecyl sulfate
      was confirmed by observing binding to the complement protein, C1q. This probe
      provides an important tool for CRP research and has the potential to improve
      clinical diagnostics that predict risk for cardiovascular disease.

PMID- 21725633
TI  - A physiologically based approach for degree-day calculation in pest phenology
      models: the case of the European corn borer (Ostrinia nubilalis Hbn.) in Northern
      Italy.
AB  - Phenological models based on degree-day accumulation have been developed to
      support the integrated pest management of many insects. Most of these models are
      based on linear relationships between temperature and development, and on daily
      time step simulations using daily minimum and maximum temperatures. This approach
      represents an approximation that does not take into account the insect
      physiological response to temperature, and daily temperature fluctuations. The
      objective of this work has been to develop a phenological model for the European
      corn borer (ECB) based on the insect physiological response to temperature and
      running at an hourly time step. Two modeling solutions based on the same generic
      compartmental system have been compared: the first based on a physiologically
      based relationship between temperature and development, and using hourly derived
      temperatures as input (HNL modeling solution); and the second based on a linear
      relationship between temperature and degree-day accumulation and using daily
      temperature (DL modeling solution). The two approaches have been compared using
      ECB moth capture data from the Piemonte region in Northern Italy. The HNL
      modeling solution showed the best results for all the accuracy indicators. The DL
      modeling solution showed a tendency to anticipate ECB phenological development
      too early. This tendency is attributable to the linear relationship between
      temperature and development, which does not take into account (1) the decline of
      this relationship at high temperatures, and (2) the daily fluctuation of
      temperature. As a consequence, degree-days accumulation is accelerated in the DL
      modeling solution and the phenological development anticipated.

PMID- 21725634
TI  - Flurbiprofen axetil enhances analgesic effect of fentanyl associated with
      increase in beta-endorphin levels.
AB  - PURPOSE: To examine the analgesic effect of preoperative administration of
      flurbiprofen axetil and that of postoperative administration of a combination of
      flurbiprofen axetil and fentanyl, as well as perioperative plasma beta-endorphin
      (beta-EP) levels in patients undergoing esophagectomy. METHODS: Forty-five
      patients were randomly divided into three groups: group A: 100 mg flurbiprofen
      axetil preoperative, 10 MUg/kg fentanyl + 10 ml placebo postoperative; group B:
      100 mg flurbiprofen axetil preoperative, 10 MUg/kg fentanyl + 100 mg flurbiprofen
      axetil postoperative; group C: 10 ml placebo preoperative, 10 MUg/kg fentanyl +
      10 ml placebo postoperative. Postoperative analgesia was achieved by intravenous
      infusion containing flurbiprofen axetil and/or fentanyl at 2.0 ml/h (total
      volume, 100 ml) using infusion pumps. The beta-EP was measured at preanesthesia
      (T(1)), the end of surgery (T(2)), 24 h (T(3)), and 48 h (T(4)) after surgery.
      Visual analog scale scores (VAS) at T3, T4 (at rest), and rescue analgesic
      tramadol requirement was recorded. RESULTS: The VAS of group B was significantly
      lower than group A and C (P < 0.01) at T(3) and T(4). The beta-EP levels at T(2)
      T(4) in group A did not differ significantly from those at T(1) (P > 0.05);
      however, the beta-EP levels in group B at T(3)-T(4) increased significantly (P <
      0.05), while those in group C increased at T(2) and decreased at T(4) (P < 0.05).
      The beta-EP levels in group B at T(3) and T(4) were the highest as compared to
      its levels in groups A and C (P < 0.01). Tramadol consumption in group B was
      significantly lower than in groups A and C (P < 0.01). CONCLUSION: These results
      show that flurbiprofen axetil enhances the analgesic effect of fentanyl
      associated with increase in beta-EP levels.

PMID- 21725635
TI  - Convulsion and cardiorespiratory collapse with first epidural test dose.

PMID- 21725636
TI  - Regulation of carcinoembryonic antigen release from colorectal cancer cells.
AB  - Clinical and experimental evidence suggest that circulating carcinoembryonic
      antigen (CEA) released from tumor cells has an instrumental role in colorectal
      cancer-liver metastasis. However, the precise mechanism of the regulation of the
      CEA release from cancer cells is not known. We investigated if the rate of CEA
      and another GPI-anchored protein, alkaline phosphatase (AP) release is correlated
      with cellular glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD)
      expression. We also evaluated the effects of phosphatidic acid (PA), a compound
      known to inhibit GPI-PLD activity, on the CEA and AP release from colon cancer
      cells. The expression of CEA, GPI-PLD, and AP in five colon carcinoma cells
      (LS180, Caco2, SW742, SW1116, and HT29/219) was verified by immunoblot and real
      time RT-PCR analysis. The amounts of CEA and AP released into cell culture media
      were determined using ELISA and a colorimetric assay, respectively. We examined
      the effects of PA (20-100 MUM) on CEA and AP release from LS180 cells. All five
      cancer cell lines analyzed expressed GPI-PLD protein. While there was a positive
      relationship between AP release and the levels of GPI-PLD transcript expression,
      we found no direct correlation between CEA released from cancer cells and the GPI
      PLD mRNA expression level. However, the rate of CEA release was positively
      associated with the level of CEA transcript expression. In comparison to
      controls, the release of GPI-anchored CEA and AP, but not CA19-9 was inhibited
      significantly by both crude and pure phosphatidic acid (by 56 and 54.5%,
      respectively). Using PA for inhibiting CEA release from cancer cells may have
      therapeutic application in preventing CRC-liver metastasis.

PMID- 21725637
TI  - Characterization of PROFILIN genes from allotetraploid (Gossypium hirsutum)
      cotton and its diploid progenitors and expression analysis in cotton genotypes
      differing in fiber characteristics.
AB  - The actin-binding protein profilin (PRF) plays an important role in cell growth
      and expansion by regulating the organization of the actin filaments. Recent
      studies have reported association between fiber elongation in cultivated cotton
      (Gossypium hirsutum) and PRF expression. In the present study, we cloned four
      genomic clones from allotetraploid cotton (G. hirsutum) and its putative diploid
      progenitors (G. arboreum and G. raimondii) designated GhPRF1_A, GhPRF1_D, GaPRF1,
      and GrPRF1 encoding cotton PRF and characterized their genomic structure,
      phylogenetic relationships and promoter structure. Sequence analysis of the
      coding regions of all clones resulted in a single protein product which revealed
      more than 80% similarity to most plant PRFs and a typical organization with an
      actin-binding and a polybasic phospholipid binding motif at the carboxy terminus.
      DNA blot hybridization suggested that PRF gene is present with more than one copy
      in the allotetraploid species G. hirsutum. Expression analysis performed in
      various organs of cultivated cotton revealed that the PRF gene was preferentially
      expressed in cotton fibers. Very low levels of expression were observed in whole
      flowers, while PRF transcripts were not detected in other organs examined.
      Furthermore, higher levels of expression were observed at the early stages of
      cotton fiber development (at 10 days post anthesis), indicative that this gene
      may play a major role in the early stages of cotton fiber development.
      Quantitation of the expression by real-time PCR revealed higher expression levels
      in a G. hirsutum variety with higher fiber percentage compared to a variety with
      lower percentage. In addition, higher levels of expression were found in
      cultivated allotetraploid G. barbadense cotton species with higher fiber length
      in comparison to cultivated allotetraploid G. hirsutum.

PMID- 21725638
TI  - Alpha-tubulin (CsTUA) up-regulated during winter dormancy is a low temperature
      inducible gene in tea [Camellia sinensis (L.) O. Kuntze].
AB  - The present manuscript describes cloning and expression characterization of alpha
      tubulin (CsTUA) gene in an evergreen tree tea [Camellia sinensis (L.) O. Kuntze]
      in response to winter dormancy (WD), abiotic stresses (sodium chloride,
      polyethylene glycol, and hydrogen peroxide) and plant growth regulators [abscisic
      acid (ABA), gibberellic acid (GA(3)), indole-3-butyric acid (IBA), and 6
      benzylaminopurine (BA)]. CsTUA encoded a putative protein of 449 amino acids with
      a calculated molecular weight of 49.6 kDa and an isoelectric point (pI) of 5.09.
      CsTUA shared 76-84 and 90-95% identity at nucleotide and amino acid level,
      respectively with TUA genes from other plant species. During the period of active
      growth (PAG), CsTUA showed maximum expression in floral buds as compared to leaf,
      stem, fruit and root. Though the transcript was not detectable in the younger
      leaf tissue during the PAG, the expression was induced within 24 h of the low
      temperature (LT) treatment. The expression was not modulated by the plant growth
      regulators either in the tissue harvested during PAG or during WD. It was
      interesting to record that the expression of CsTUA was up-regulated in response
      to sodium chloride, polyethylene glycol, and hydrogen peroxide. Data has been
      discussed on the possible role of CsTUA in imparting tolerance to stresses
      including to LT so that the tea does not exhibit deciduous nature during winters.

PMID- 21725639
TI  - Proteomic analysis of peritrophic membrane (PM) from the midgut of fifth-instar
      larvae, Bombyx mori.
AB  - The insect peritrophic membrane (PM), separating midgut epithelium and intestinal
      contents, is protective lining for the epithelium and plays the important role in
      absorption of nutrients, and also is the first barrier to the pathogens ingested
      through oral feeding. In order to understand the biological function of silkworm
      larval PM, shotgun liquid chromatography tandem mass spectrometry (LC-MS/MS)
      approach was applied to investigate its protein composition. Total 47 proteins
      were identified, of which 51.1% of the proteins had the isoelectric point (pI)
      within the range of 5-7, and 53.2% had molecular weights within the range 15-45
      kDa. Most of them were found to be closely related to larval nutrients metabolism
      and innate immunity. Furthermore, these identified proteins were annotated
      according to Gene Ontology Annotation in terms of molecular function, biological
      process and cell localization. Most of the proteins had catalytic activity,
      binding activity and transport function. The knowledge obtained from this study
      will favour us to well understand the role of larval PM in larval physiological
      activities, and also help us to find the potential target and design better
      biopesticides to control pest, particularly the Lepidoptera insect.

PMID- 21725641
TI  - [Principles of multidetector-row computed tomography : part 1. Technical design
      and physicotechnical principles].
AB  - Despite the unchanged retention of the fundamental technical and physical
      principles since its first clinical application in the year 1972, computed
      tomography (CT) constitutes a mainstay of present day radiological diagnostics.
      In conjunction with the sub-second gantry rotation times now achieved numerous
      technical improvements, such as helical scanning and the development of high
      performance X-ray tubes as well as multi-row detectors with up to 320 rows allow
      large areas to be examined with high image quality within only a few seconds. On
      the basis of these advancements modern multidetector-row CT (MDCT) enables high
      resolution slice or volume imaging of the anatomy as well as multiphase and
      perfusion examinations. An end to innovations in the field of MDCT is not yet
      foreseeable and further technical developments will open up new radiodiagnostic
      indications thereby broadening the spectrum of clinical applications of MDCT in
      the future.

PMID- 21725640
TI  - Isolation of Ty1-copia retrotransposon in myrtle genome and development of S-SAP
      molecular marker.
AB  - Long terminal repeat (LTR)-retrotransposons are mobile genetic elements that are
      ubiquitous in plants and constitute a major portion of their nuclear genomes. LTR
      retrotransposons possess unique properties that make them appropriate for
      investigating relationships between populations, varieties and closely related
      species. Myrtus communis L. is an evergreen shrub growing spontaneously
      throughout the Mediterranean area. Accessions show significant variations for
      agriculturally important traits, so the development of specific molecular markers
      for conservation and characterization of myrtle germplasm is desirable to
      conserve biodiversity. In this study, we isolated the first retrotransposon Ty1
      copia-like element (Tmc1) in Myrtus communis L. genome and used this as a
      molecular marker. We successfully employed the S-SAP marker system to
      specifically characterize four myrtle accessions belonging to different areas in
      the province of Caserta (Italy). The high level of polymorphism detected in
      isolated LTRs, make Tmc1 a good molecular marker for this species. Our findings
      confirm that retrotransposon-based molecular markers are particularly valuable
      tools for plant molecular characterization studies.

PMID- 21725642
TI  - Non steroidal anti-inflammatory drugs modulate the physicochemical properties of
      plasma membrane in experimental colorectal cancer: a fluorescence spectroscopic
      study.
AB  - According to "fluid-mosaic model," plasma membrane is a bilayer constituted by
      phospholipids which regulates the various cellular activities governed by many
      proteins and enzymes. Any chemical, biochemical, or physical factor has to
      interact with the bilayer in order to regulate the cellular metabolism where
      various physicochemical properties of membrane, i.e., polarization, fluidity,
      electrostatic potential, and phase state may get affected. In this study, we have
      observed the in vivo effects of a pro-carcinogen 1,2-dimethylhydrazine
      dihydrochloride (DMH) and the two non steroidal anti-inflammatory drugs (NSAIDs);
      sulindac and celecoxib on various properties of the plasma membrane of
      colonocytes, i.e., electric potential, fluidity, anisotropy, microviscosity,
      lateral diffusion, and phase state in the experimentally induced colorectal
      cancer. A number of fluorescence probes were utilized like membrane fluidity and
      anisotropy by 1,6-diphenyl-1,3,5-hexatriene, membrane microviscosity by Pyrene,
      membrane electric potential by merocyanine 540, lateral diffusion by N-NBD-PE,
      and phase state by Laurdan. It is observed that membrane phospholipids are less
      densely packed and therefore, the membrane is more fluid in case of
      carcinogenesis produced by DMH than control. But NSAIDs are effective in
      reverting back the membrane toward normal state when co-administered with DMH.
      The membrane becomes less fluid, composed of low electric potential phospholipids
      whose lateral diffusion is being prohibited and the membrane stays mostly in
      relative gel phase. It may be stated that sulindac and celecoxib, the two NSAIDs
      may exert their anti-neoplastic role in colorectal cancer via modifying the
      physicochemical properties of the membranes.

PMID- 21725643
TI  - A novel insight into the heme and NO/CO binding mechanism of the alpha subunit of
      human soluble guanylate cyclase.
AB  - Human soluble guanylate cyclase (sGC), a critical heme-containing enzyme in the
      NO-signaling pathway of eukaryotes, is an alphabeta heterodimeric hemoprotein.
      Upon the binding of NO to the heme, sGC catalyzes the conversion of GTP to cyclic
      GMP, playing a crucial role in many physiological processes. However, the
      specific contribution of the alpha and beta subunits of sGC in the intact heme
      binding remained intangible. The recombinant human sGC alpha1 subunit has been
      expressed in Escherichia coli and characterized for the first time. The heme
      binding and related NO/CO binding properties of both the alpha1 subunit and the
      beta1 subunit were investigated via heme reconstitution, UV-vis spectroscopy, EPR
      spectroscopy, stopped-flow kinetics, and homology modeling. These results
      indicated that the alpha1 subunit of human sGC, lacking the conserved axial
      ligand, is likely to interact with heme noncovalently. On the basis of the
      equilibrium and kinetics of CO binding to sGC, one possible CO binding model was
      proposed. CO binds to human sGCbeta195 by simple one-step binding, whereas CO
      binds to human sGCalpha259, possibly from both axial positions through a more
      complex process. The kinetics of NO dissociation from human sGC indicated that
      the NO dissociation from sGC was complex, with at least two release phases, and
      human sGCalpha259 has a smaller k (1) but a larger k (2). Additionally, the role
      of the cavity of the alpha1 subunit of human sGC was explored, and the results
      indicate that the cavity likely accommodates heme. These results are beneficial
      for understanding the overall structure of the heme binding site of the human sGC
      and the NO/CO signaling mechanism.

PMID- 21725644
TI  - A case of lymphoplasmacyte-rich meningioma of the jugular foramen.
AB  - Lymphoplasmacyte-rich meningioma (LPRM), the most rare variant of meningiomas,
      features extensive lymphoplasmacytic infiltrates. Although the jugular foramen
      (JF) is occasionally involved by several types of tumor, such as paragangliomas
      and schwannomas, meningioma in the JF is an infrequent disease. Here we present
      an extremely rare case of LPRM found in the JF. A 55-year-old woman complained of
      paresis in her right eyelid and palsy in the right side of her lip. Hoarseness
      and dysphagia also occurred in the following month. Radiologic examinations
      disclosed a mass lesion in the right JF, and the tumor was operatively removed.
      Microscopically, the tumor was composed of extensive lymphoplasmacytic
      infiltration with mild vascular proliferation and scattered sheets of epithelioid
      cells with plump cytoplasm. Although the obvious whorl formation or psammoma
      bodies were not observed, by immunochemistry the epithelioid cells were positive
      for epithelial membrane antigen and also progesterone receptor, indicating a
      meningothelial cell origin. Considering the histological and radiologic findings,
      we finally diagnosed the case as LPRM, making this the second reported case of
      LPRM in the JF.

PMID- 21725645
TI  - Oligodendroglial ganglioglioma.
AB  - Gangliogliomas are rare tumors of the central nervous system, usually containing
      neoplastic ganglion cells and astrocytic components. Few cases of ganglioglioma
      containing only oligodendrocytic tissue have been reported to date. We present a
      case of a 40-year-old woman with ganglioglioma consisting mostly of
      oligodendroglial components. Magnetic resonance imaging showed a well-demarcated
      cystic lesion with slight perifocal edema in the right parietal lobe. The wall of
      the cyst was not enhanced after administration of Gd-DTPA contrast media. The
      mass was totally resected. Histological examination showed a mixture of two
      distinct components: oligodendroglioma and dysplastic ganglions. The first
      component was diffusely proliferated cells with round nuclei and perinuclear
      halo; the second showed marked nucleoli and basophilic cytoplasm containing Nissl
      bodies. Immunohistochemical study of the oligodendroglial component was positive
      for OLIG 2 and NKX2.2 but negative for synaptophysin. In addition, LOH of 1p/19q
      was detected by FISH. Although no adjuvant therapy was carried out, follow-up MRI
      showed no recurrence of the tumor 41 months after the operation.

PMID- 21725646
TI  - [Jewish urologists in Hamburg: eight biographies from Imperial Germany to Nazi
      Germany].
AB  - Before the Nazis seized power in 1933, eight Jewish urologists practiced in the
      city of Hamburg: Otto Einzig, Moritz Furst, Ernst Frankel, Wilhelm Haas,
      Friedrich Luhrse, Paul Rosenberg, Sigmund Wertheim and Erich Wohlauer. This
      contribution traces their lives and careers. One of them was murdered at the
      Theresienstadt concentration camp and seven emigrated to the USA, Sweden and
      South Africa. One emigrant committed suicide shortly after arriving in the USA
      and while the other six continued to practice medicine, they did so under
      precarious conditions.

PMID- 21725647
TI  - [Securing the future through research - light on the horizon?].
AB  - Research is more important than ever for urology as a clinical specialty. The
      enormous advances being achieved in molecular medicine should not develop outside
      the realm of urology. In fact, implementing them in urology serves to guarantee
      the further existence of our specialty with its current clinical scope. If drug
      therapy for cancer is to remain an enduring part of urology or if kidney
      transplantation is to continue to be an integral part of urology and not belong
      to transplant surgery, then the expertise in these clinical entities and
      understanding of their pathogenetic relationships must be found in urology. As a
      result, research must be an essential part of our specialty on the one hand and
      the results of research must be applied to the whole extent of urology on the
      other hand.

PMID- 21725648
TI  - [Prolapse surgery: vaginal mesh or sacropexy].
AB  - The systematic assessment of common therapy concepts for female genital prolapse
      has led to a better understanding of the functional and anatomical connections
      and given proof of the lasting effectiveness of traditional surgery. Besides the
      defined evidence-based therapy strategies in vaginal prolapse repair, vaginal
      meshes are being used with increasing frequency. The lack of reliable therapy
      recommendations for these methods sounds us a note of caution in their
      application and underlines the necessity of standardised performance in
      experienced departments.

PMID- 21725649
TI  - [Therapy-refractory overactive bladder: alternative treatment approaches].
AB  - The treatment of patients with overactive bladder (OAB) refractory to
      conventional treatment is gaining clinical significance. This article intends to
      review alternative therapy options for patients with OAB refractory to
      conventional treatment. A search of the PubMed database as well as the abstracts
      presented at the European Association of Urology and the American Urological
      Association annual meetings was conducted. Keywords used during this search
      included overactive bladder (OAB) refractory to conventional treatment,
      electromotive drug administration (EMDA), sacral neuromodulation, augmentation
      cystoplasty and cystectomy. Eighteen articles with an adequate number of patients
      were identified. All articles published before 2001 were not included in this
      analysis. Because of first-line treatment failure, 30% of the patients required
      alternative treatment. This included EMDA, botulinum toxin injections into the
      detrusor, sacral neuromodulation, augmentation cystoplasty or cystectomy. Based
      on this review it appears that a significant improvement in micturition
      parameters, continence and in quality of life was achieved. Overall EMDA,
      intradetrusor injections of botulinum toxin and sacral neuromodulation seem to be
      highly effective and safe. Augmentation cystoplasty or cystectomy remains the
      last choice of treatment in refractory cases.Overall EMDA, intradetrusor
      injections of botulinum toxin and sacral neuromodulation seem to be highly
      effective and safe. Augmentation cystoplasty or cystectomy remains to be the last
      choice of treatment in refractory cases.

PMID- 21725654
TI  - Effects of physical activity on common side effects of breast cancer treatment.
AB  - Motivating women with breast cancer to engage in regular physical activity may be
      an enormous challenge given the common side effects of breast cancer treatment.
      The objective of this narrative review is to briefly summarize recent research
      evidence examining the influence of physical activity on commonly occurring side
      effects of breast cancer treatment. Overall, current research evidence indicates
      that regular participation in physical activity after breast cancer diagnosis may
      mitigate common side effects of breast cancer adjuvant therapy, including
      fatigue, depression, impaired quality of life, decreased muscular strength,
      decreased aerobic capacity, and weight gain. Future research could examine the
      influence that physical activity has on the effectiveness of breast cancer
      treatment. Implications for health care professionals are discussed.

PMID- 21725655
TI  - Topoisomerase II alpha expression and the Ki-67 labeling index correlate with
      prognostic factors in estrogen receptor-positive and human epidermal growth
      factor type-2-negative breast cancer.
AB  - BACKGROUND: Topoisomerase II alpha (Topo IIa) is involved in DNA replication and
      is a molecular target for anthracycline-based chemotherapy. The Ki-67 labeling
      index (LI) is an evaluation of tumor cell proliferation. The objective of this
      study was to evaluate relationships among Topo IIa expression, the Ki-67 LI, and
      prognostic factors in estrogen receptor (ER)-positive, human epidermal growth
      factor type-2 (HER2)-negative breast cancer. MATERIALS AND METHODS: Seventy-one
      patients were diagnosed with ER-positive, HER2-negative breast cancer between
      July 2003 and December 2004. Formalin-fixed, paraffin-embedded tumor specimens
      were stained for Topo IIa expression and Ki-67 LI. We investigated the
      correlation of the level of Topo IIa expression and the Ki-67 LI with clinical
      factors such as age, tumor size, progesterone receptor status, nodal status,
      nuclear grade, and lymphovascular invasion (LVI). RESULTS: Statistically
      significant differences were observed between Topo IIa overexpression, nuclear
      grade (p = 0.036), and LVI (p = 0.029). Topo IIa overexpression was statistically
      correlated with the Ki-67 LI (p < 0.0001). A statistically significant difference
      was observed between the Ki-67 LI and nuclear grade (p = 0.01). Survival analysis
      revealed the significant prognostic value of Ki-67 LI in patients with ER
      positive, HER2-negative breast cancer (p = 0.003). CONCLUSIONS: Ki-67 LI is a
      strong prognostic factor in ER-positive HER2-negative breast cancer. Topo IIa
      overexpression was significantly correlated with the Ki-67 LI, nuclear grade, and
      LVI. These findings suggest use of Topo IIa expression as a proliferation marker
      and a prognostic factor in ER-positive, HER2-negative breast cancer.

PMID- 21725656
TI  - Transcutaneous detection and direct approach to the sentinel node using axillary
      compression technique in ICG fluorescence-navigated sentinel node biopsy for
      breast cancer.
AB  - BACKGROUND: Indocyanine green (ICG) fluorescence navigation is a useful option in
      sentinel node biopsy (SNB) for breast cancer. However, several technical
      difficulties still exist. Since the sentinel node (SN) cannot be recognized over
      the skin, subcutaneous lymphatic vessels (LVs) must be carefully dissected
      without injury. In addition, the dissecting procedures are often interrupted by
      turning off the operating light during fluorescence observation. In this report,
      we introduce a new approach using the axillary compression technique to overcome
      these problems. MATERIALS AND METHODS: In the original procedure of the ICG
      fluorescence method, the subcutaneous lymphatic drainage pathway from the breast
      to the axilla was observed in fluorescence images, but no signal could be
      obtained in the axilla. When the axillary skin was compressed against the chest
      wall using a plastic device, the signals from the deeper lymphatic structures
      could be observed. By tracing the compression-inducible fluorescence signal
      towards the axilla, transcutaneous detection and direct approach to the SN were
      achieved. The benefit of this approach is that there is no risk of injury of LVs,
      and the procedures are interrupted less frequently by fluorescence observation.
      The axillary compression technique was used in 50 patients with early breast
      cancer. RESULTS: SNs were successfully removed in all patients. Transcutaneous
      detection and direct approach were possible in 47 patients. This approach was
      also effective in obese patients. CONCLUSIONS: Axillary compression technique is
      a simple way to facilitate the surgical procedures of ICG fluorescence-navigated
      SNB for breast cancer.

PMID- 21725657
TI  - Acute systemic hypotension after arteriovenous fistula construction in a patient
      with severe aortic stenosis.
AB  - We report the case of a 53-year-old hemodialysis patient with severe aortic
      stenosis, who developed acute systemic hypoperfusion after arteriovenous fistula
      (AVF) construction. He presented with hypotension and repeated syncope soon after
      distal radiocephalic AVF construction, and finally developed a respiratory
      arrest. His blood pressure and hemodynamics recovered promptly by sub-emergent
      aortic valve replacement surgery. In the present case, the heart with severe
      aortic stenosis could not increase cardiac output in response to the reduction in
      peripheral vascular resistance caused by the AVF. High-output heart failure, a
      relatively rare AVF-associated disorder, occurs with an excessive AVF flow,
      usually more than 3 L/min or 30% of cardiac output. However, heart failure may
      develop soon after construction of an AVF with a moderate blood flow if a
      patient's cardiac function is severely impaired. In addition, heart failure may
      improve with AVF preservation if the underlying heart disease is treatable.

PMID- 21725658
TI  - Nephrologist care for 12 months or more increases hemodialysis initiation with
      permanent vascular access.
AB  - BACKGROUND: The objective of this study was to evaluate the effect of early
      referral (ER) to nephrologists on the type of vascular access (VA) available for
      use at the time of initiation of maintenance hemodialysis (HD). In patients who
      have been followed by nephrologists for less than 3 months, management before the
      initiation of HD is often insufficient and urgent initiation of HD is often
      necessary; therefore, patients in this study were limited to those who had been
      followed for at least 3 months by nephrologists. METHODS: Nine hundred and forty
      patients at 9 institutions affiliated to our study group were enrolled in this
      retrospective observational study. We defined patients followed up by
      nephrologists for at least 12 months as the early referral (ER) group and those
      followed for between 3 and 12 months as the late referral (LR) group. The type of
      VA available for use at the initiation of maintenance HD was compared between the
      groups. RESULTS: Early referral was found to be significantly associated with the
      availability of a permanent VA, which included an arteriovenous fistula or
      arteriovenous graft, at the time of initiation of HD (odds ratio [OR] 1.705; P =
      0.001). Multivariate analysis also revealed ER to be significantly associated
      with the availability of a permanent VA (OR 1.509; P = 0.023). CONCLUSION: Early
      referral was shown to be advantageous for increasing the likelihood of
      availability of a permanent VA, even after patients who had been followed up for
      less than 3 months by nephrologists were excluded.

PMID- 21725659
TI  - Regulation of cytochrome P4501A by protein kinase C: the role of heat shock
      protein70.
AB  - Carbofuran is a pesticide, which is used throughout the world as a nematicide and
      an acaricide. This pesticide integrates into living organisms through aquatic
      ecosystem. In earlier report, we had demonstrated that cytochrome P4501A was
      induced in cultured catfish hepatocytes in response to carbofuran, which might be
      responsible for the detoxification of this pesticide. As the underlying signaling
      mechanism associated with induction and regulation of cytochrome P4501A has not
      yet been well defined, we therefore in the present study have investigated to
      identify the regulatory network of cytochrome P4501A in catfish liver or cultured
      hepatocytes by targeting several key signaling molecules such as phosphatidyl
      inositol (PI) or protein kinase C (PKC), which are critical molecules for many
      important pathways. PKC and heat shock protein70 (HSP70) have been shown to be
      induced in response to carbofuran in catfish hepatocytes. Results also indicate
      that induction of CYP1A is modulated by HSP70 and PKC in fish hepatocytes. Thus
      our data shed light on the regulation of EROD activity, which has been used as a
      bio-monitoring tool for measuring aquatic pollution.

PMID- 21725660
TI  - [Visual development and amblyopia prophylaxis in pediatric glaucoma].
AB  - In children with congenital glaucoma the functional long-term result is often
      disappointing even if the intraocular pressure is well controlled. The reason for
      this discrepancy is attributed to amblyogenic factors responsible for interfering
      with normal visual development. These amblyogenic factors are corneal edema,
      irregular astigmatism and non-corrected ametropia as monocular causes. Binocular
      causes are anisometropia-induced suppression and strabismus. Full ametropic
      correction and a very early prophylaxis and treatment of amblyopia with a close
      follow-up are mandatory to reduce amblyogenic visual impairment in children with
      congenital glaucoma.

PMID- 21725661
TI  - Evaluation of a simultaneous detection kit for the glutamate dehydrogenase
      antigen and toxin A/B in feces for diagnosis of Clostridium difficile infection.
AB  - Rapid detection kits for toxin A/B in feces are widely used as a diagnostic tool
      for Clostridium difficile infection (CDI). Their low sensitivity, however, has
      been considered a problem. In this study, we evaluated a new rapid diagnostic kit
      for simultaneous detection of the glutamate dehydrogenase (GDH) antigen and toxin
      A/B, C. DIFF QUIK CHEK COMPLETE. A total of 60 stool specimens from 60 patients
      with antibiotic-associated diarrhea were examined. Using C. difficile culture as
      the reference method, the GDH portion of this kit indicated a sensitivity,
      specificity, and negative predictive value of 100, 93.3, and 100%, respectively.
      The toxin A/B portion showed a sensitivity and specificity of 78.6 and 96.9%,
      respectively, compared to the culture results of toxin B-positive C. difficile
      (toxigenic culture). Of the 23 specimens that showed "dual positives" for GDH and
      toxin A/B, 22 were toxigenic culture positive, whereas C. difficile culture was
      negative in all the 28 specimens that showed "dual negatives" for GDH and toxin
      A/B. Of the nine "GDH-positive and toxin A/B-negative" specimens, six exhibited
      positive results by toxigenic culture. Results showing "dual positives" and "dual
      negatives" for GDH and toxin A/B can be reported as "true positive" and "true
      negative," respectively, whereas additional testing for confirmation, such as
      toxigenic culture, is required for specimens with discrepant results. Diagnostic
      algorithms, utilizing the simultaneous detection kit for GDH and toxin A/B as an
      initial screening test, may be useful for accurate and efficient diagnosis of CDI
      as well as the control of healthcare-associated infections.

PMID- 21725662
TI  - [Extension first technique for TKA implantation].
AB  - OBJECTIVE: Surgical technique in total knee arthroplasty (TKA) to combine the
      femur first and tibia first techniques in order to reduce surgical mistakes
      regarding rotation and alignment. INDICATIONS: Symptomatic arthritis of the knee.
      CONTRAINDICATIONS: General contraindications for TKA. SURGICAL TECHNIQUE: Osseous
      preparation starting with a distal femur cut. Then the proximal tibia cut is
      accomplished and the knee is balanced in extension after checking for correct
      alignment. Bone-referenced positioning of the femoral cutting block for further
      preparation of the femur. Finally, the rotation of the femur is checked in 90
      degrees  of flexion by means of ligament tension. If required, the rotation is
      checked and the flexion gap balanced, respectively. POSTOPERATIVE MANAGEMENT:
      Mobilization with weight bearing and range of motion as tolerated. RESULTS: In a
      prospective study, 267 knees (160 women, 107 men, average age of 69.3 [46-89]
      years) were followed up preoperatively and after 6 weeks. The clinical results
      were based on the American Knee Society score. The scores were 48.9 (32-68)
      preoperatively and 86.5 (75-100) at follow-up. Radiologically 92.1% of the knees
      showed a malposition <3 degrees .

PMID- 21725663
TI  - [Littler tenodesis for correction of swan neck deformity in rheumatoid
      arthritis].
AB  - OBJECTIVE: Correction of swan neck deformity at the PIP and DIP joint by
      reconstruction of the oblique retinacular ligament through palmar transposition
      of one distally pedicled lateral band (oblique retinacular ligament
      reconstruction (ORL) = Littler II). INDICATIONS: Rheumatoid swan neck deformity
      Nalebuff stages I-III (dynamic, partially contracted, contracted). The swan neck
      deformity should be of articular origin. CONTRAINDICATIONS: Advanced radiologic
      changes of the PIP joint (Larsen 3-4) [12]. Extrinsic and intrinsic causes of
      swan neck deformity. Flexor tendon synovitis. SURGICAL TECHNIQUE: Dorsal approach
      to the PIP joint. One lateral band is sectioned proximally at the level of the
      musculotendinous junction. It is then isolated from the extensor apparatus and
      left pedicled distal at the insertion. The isolated lateral band is then passed
      underneath the Cleland ligament from distal to proximal and is sutured to the
      distal edge of the A2 pulley. The correct tension of the tenodesis achieves
      flexion at the PIP joint and extension at the DIP joint. In contracted and
      partially contracted joints, the PIP joint is temporarily transfixed. Depending
      on the clinical findings, a synovectomy or dorsal arthrolysis of the PIP joint
      must be performed. POSTOPERATIVE MANAGEMENT: Immediate postoperative mobilization
      of the PIP joint for flexion. A figure-of-eight finger splint has to be worn for
      12 weeks. The splint must allow full PIP flexion and limit extension over 20-30
      degrees  of flexion. In case of temporary transfixation of the PIP joint, wire
      removal after 4-6 weeks and start of mobilization. Passive extension over 20-30
      degrees  of flexion only after 12 weeks. RESULTS: From 2004-2007, 30 PIP joints
      in 20 rheumatoid patients were treated for swan neck deformity. In all cases, the
      original method as described by Littler was used. A change of the procedure due
      to insufficiency of the Cleland ligament or the A2 pulley was not necessary in
      any of the cases. After a mean of 22 months, 26 PIP joints in 17 patients could
      be followed up. In 12 PIP joints, the deformity was partially contracted, in two
      joints contracted. In 10 joints, a dorsal arthrolysis had to be performed, while
      a lengthening of the medial band was performed in 1 patient. The swan neck
      deformity could be compensated in all cases. Preoperative hyperextension of a
      mean 21 degrees  could be reduced to a mean 24 degrees  of flexion
      postoperatively. The ROM did not change much but was shifted from the extension
      sector to the flexion sector of the PIP joint. In no case were complications or
      recurrence of the deformity noted. Pain could be reduced in all patients except
      one. The radiologic joint situation was Larsen stage 2.2 preoperatively and 2.3
      postoperatively.

PMID- 21725664
TI  - [Closed irrigation system for pyogenic flexor tenosynovitis of the hand].
AB  - OBJECTIVE: Treatment of pyogenic flexor tenosynovitis within the osteofibrous
      channel of the thumb and finger by insertion of a closed irrigation system.
      INDICATIONS: Pyogenic tenosynovitis of the flexor tendons of the hand.
      CONTRAINDICATIONS: Necrosis of the flexor tendons or flexor tendon sheath,
      gangrene of the finger, extensive loss of soft tissue. SURGICAL TECHNIQUE:
      Insertion of a flexible irrigation catheter via a guide wire into the flexor
      tendon sheath and a vacuum suction drain into the finger or the palm of the hand.
      Extensive exploration of the flexor tendon sheath is not mandatory. POSTOPERATIVE
      MANAGEMENT: On days 0-3 continuous irrigation, on day 4 change of the irrigation
      catheter to suction, on day 5 removal of the irrigation catheter, on day 6
      removal of the suction drain, on day 7 start of exercise. Irrigation volume:
      about 500-1500 ml/24 h isotonic solution. RESULTS: Of 35 patients treated for
      flexor tenosynovitis by closed irrigation, 33 were reviewed. There were 19 male
      patients and 14 female patients. The average age at the time of surgery was 51 (8
      85) years. Hospital stay was 8.9 (3-26) days on average. At the time of follow
      up, the average grip strength was 84% (23-163%) of the unaffected side. Pain at
      rest was 0.2 (0-4), pain during exercise 1.2 (0-8) on the analogue scale, the
      DASH score was 16.8 (0-58) points. According to the rating system for flexor
      tendon function, there were one poor, one fair, five good, and 26 excellent
      results.

PMID- 21725665
TI  - Tissue factor expression in ovarian cancer: implications for immunotherapy with
      hI-con1, a factor VII-IgGF(c) chimeric protein targeting tissue factor.
AB  - We evaluated the expression of tissue factor (TF) in ovarian cancer (EOC) and the
      potential of hI-con1, an antibody-like molecule targeting TF, as a novel form of
      therapy against chemotherapy-resistant ovarian disease. We studied the expression
      of TF in 88 EOC by immunohistochemistry (IHC) and real-time-PCR (qRT-PCR) and the
      levels of membrane-bound-complement-regulatory-proteins CD46, CD55 and CD59 in
      primary EOC cell lines by flow-cytometry. Sensitivity to hI-con1-dependent-cell
      mediated-cytotoxicity (IDCC), complement-dependent-cell-cytotoxicity and
      inhibition of IDCC by gamma-immunoglobulin were evaluated in 5-h (51)chromium
      release-assays. Cytoplasmic and/or membrane TF expression was observed in 24 out
      of 25 (96%) of the EOC samples tested by IHC, but not in normal ovarian-tissue.
      EOC with clear cell histology significantly overexpress TF when compared to
      serous, endometrioid, or undifferentiated tumors by qRT-PCR. With a single
      exception, all primary EOC that overexpressed TF demonstrated high levels of
      CD46, CD55 and CD59 and regardless of their histology or resistance to
      chemotherapy, were highly sensitive to IDCC. The effect of complement and
      physiologic doses of gamma-immunoglobulin on IDCC in ovarian cancer cell lines
      overexpressing TF was tumor specific and related to the overexpression of CD59 on
      tumor cells. Small-interfering-RNA-mediated knockdown of CD59 expression in
      ovarian tumors significantly increased hI-con1-mediated cytotoxic activity in
      vitro. Finally, low doses of interleukin-2 further increased the cytotoxic effect
      induced by hI-con1 (P < 0.01). hI-con1 molecule induces strong cytotoxicity
      against primary chemotherapy-resistant ovarian cancer cell lines overexpressing
      TF and may represent a novel therapeutic agent for the treatment of ovarian
      tumors refractory to standard treatment modalities.

PMID- 21725666
TI  - Successful coronary intervention of chronic total occlusion of the right coronary
      artery by ipsilateral injection via an isolated conus artery.
AB  - A conus artery is sometimes a good collateral source for the left anterior
      descending coronary artery and the right coronary artery (RCA). In some cases,
      the conus artery arises independently of the RCA from a separate orifice, which
      is called an isolated conus artery. The conus artery is often missed by
      angiography for RCA if a catheter is deeply engaged. This case report describes a
      percutaneous coronary intervention of chronic total occlusion of the proximal RCA
      with good collateral circulation from an isolated conus artery by super-selective
      ipsilateral injection via the artery.

PMID- 21725668
TI  - Applying the National Institute for Clinical Excellence criteria to patients
      treated with the GenousTM Bio-engineered R stentTM: a sub-study of the e-HEALING
      (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide
      registry.
AB  - The National Institute for Clinical Excellence (NICE) guidelines recommend the
      use of bare-metal stents (BMS) in non-complex lesions with a low risk of
      restenosis (diameter >=3 mm and lesion length <=15 mm) and the use of drug
      eluting stents (DES) in more complex lesions with a high risk of restenosis
      (diameter <3.0 mm or lesion length >15 mm). However, the guidelines were created
      based on studies evaluating BMS and DES only. We performed an analysis of
      patients undergoing non-urgent percutaneous coronary intervention with the novel
      endothelial cell capturing stent (ECS). The ECS is coated with CD34(+) antibodies
      that attract circulating endothelial progenitor cells to the stent surface,
      thereby accelerating the endothelialization of the stented area. We analyzed all
      patients enrolled in the worldwide e-HEALING registry that met the NICE criteria
      for either low-risk or high-risk lesions and were treated with >=1 ECS. The main
      study outcome was target vessel failure (TVF) at 12-month follow-up, defined as
      the composite of cardiac death or MI and target vessel revascularization (TVR). A
      total of 4,241 patients were assessed in the current analysis. At 12-month follow
      up, TVF occurred in 7.0% of the patients with low-risk lesions and in 8.8% of the
      patients with high-risk lesions (p = 0.045). When evaluating the diabetic
      patients versus the non-diabetic patients per risk group, no significant
      differences were found in TVF, MI or TVR in either risk group. The ECS shows good
      clinical outcomes in lesions carrying either a high or a low risk of restenosis
      according to the NICE guidelines with comparable rates of cardiac death,
      myocardial infarction, and stent thrombosis. The TVF rate with ECS was slightly
      higher in patients with high-risk lesions, driven by higher clinically driven
      TLR. The risk of restenosis with ECS in patients carrying high-risk lesions needs
      to be carefully considered relative to other risks associated with DES.
      Furthermore, the presence of diabetes mellitus did not influence the incidence of
      TVF in either risk group.

PMID- 21725670
TI  - Perioperative complications and adverse events after lumbar spinal surgery:
      evaluation of 1012 operations at a single center.
AB  - BACKGROUND: Lumbar surgery and associated complications are increasing as society
      is aging. However, definitions of complications after lumbar surgery have not
      been established and previous reports have varied in the definition of, and focus
      on, intraoperative or major postoperative complications. We analyzed the
      frequency and severity of perioperative complications and all minor adverse
      events in lumbar surgery at a single center. METHODS: We retrospectively reviewed
      all lumbar surgery, including decompression surgery with or without fusion, at
      Meijo Hospital over a 10-year period. Perioperative complications and all surgery
      related adverse events until 1 month postoperatively were reviewed for 1012
      operations on 918 patients (average age 54 years old). The incidence of
      intraoperative complications was compared between junior (<10 years experience of
      spine surgery) and senior (>=10 years experience) surgeons. RESULTS:
      Perioperative complications and adverse events occurred in 159 operations (15.7%)
      on 127 patients (13.8%). There were a variety of perioperative adverse events,
      including digestive problems. Of the 159 complications and events, 24 (2.4%) were
      intraoperative and 135 (13.3%) were postoperative. Incidence of intraoperative
      complications was not significantly higher for junior surgeons; however, the
      operations performed by senior surgeons were significantly more invasive.
      Complications were more frequent in elderly patients (p < 0.01) and in operations
      that were longer (p < 0.0001), had greater estimated blood loss (p < 0.0001), and
      involved use of spinal instrumentation (p < 0.0001). Psychotic symptoms occurred
      significantly more often in older patients (p < 0.001). CONCLUSION: The absence
      of a relationship between the experience of the surgeon and incidence of
      intraoperative complications may be because of the greater effect of invasive
      surgery. Although age and invasiveness were associated with more perioperative
      adverse events, we do not conclude that major surgery should be avoided for
      elderly patients. In contrast, careful focus on the surgical indication and
      procedure is required for these patients.

PMID- 21725669
TI  - Association of midregional proadrenomedullin with coronary artery stenoses, soft
      atherosclerotic plaques and coronary artery calcium.
AB  - Midregional proadrenomedullin (MR-proADM) is elevated in patients with heart
      failure and myocardial infarction. The aim of this study was to evaluate the
      association of MR-proADM with the grade of coronary artery stenosis, presence of
      coronary artery soft plaques and coronary artery calcification score (CACS),
      determined by 64-multislice computed tomography (MSCT) in patients without known
      prior cardiovascular disease. This retrospective study included 107 patients
      undergoing MSCT for confirmation (or exclusion) of coronary artery disease. MR
      proADM levels were measured in all patients. The assessment of coronary artery
      stenoses, CACS and soft coronary plaques was made by MSCT using known criteria.
      The MR-proADM [median (25th-75th percentiles)] level was 0.33 (0.21-0.43) nmol/l.
      The MR-proADM level was 0.28 (0.22-0.40) nmol/l in patients with coronary
      stenoses >=50% (n = 23) versus 0.33 (0.27-0.40) nmol/l in patients with coronary
      stenoses <50% (n = 83, P = 0.59), 0.33 (0.26-0.40) nmol/l in patients with soft
      plaques (n = 56) versus 0.33 (0.25-0.41) nmol/l in patients without soft plaques
      (n = 50, P = 0.73) and 0.33 (0.25-0.39) nmol/l in patients with CACS <200 (n =
      81) versus 0.32 (0.26-0.44) nmol/l in patients with CACS >=200 (n = 26, P =
      0.77). In multivariate analysis, the MR-proADM level was a significant correlate
      of coronary artery stenoses [odds ratio (OR) = 0.93; 95% confidence interval (CI)
      0.86-0.99; P = 0.026] and soft plaques (OR = 0.94; 95% CI 0.90-0.99; P = 0.015)
      but not of CACS (OR = 0.98; 95% CI 0.93-1.03; P = 0.36). A decreased MR-proADM
      level is an independent correlate of the presence of coronary artery disease and
      of soft atherosclerotic plaques. Patients with decreased MR-proADM levels may
      need invasive examinations to diagnose more severe forms of coronary artery
      disease.

PMID- 21725671
TI  - Secretory osteocalcin as a nondestructive osteogenic marker of tissue-engineered
      bone.
AB  - BACKGROUND AND PURPOSE: The constructs of mesenchymal stem cells and ceramics
      form bone tissue after implantation. Therefore, the constructs can include
      cultured bone (tissue-engineered bone) as bone grafts. However, the selection of
      constructs, prior to implantation, with high osteogenic potential is still
      difficult. We used a rat model to measure the secretory osteocalcin level in
      culture medium to verify that monitoring osteocalcin levels enables the selection
      of constructs with high osteogenic potential. METHODS: We prepared constructs of
      rat hydroxyapatite/cells and used different cell passages of P-1 and P-3 as well
      as different cell numbers: 1 * 10(5) and 1 * 10(6) cells/ml suspension. These
      constructs were cultured for 14 days under osteoinductive or nonosteoinductive
      conditions and implanted subcutaneously in the recipient rat. Secretory
      osteocalcin in the culture medium was measured using an enzyme-linked
      immunosorbent assay system during the culture period until day 14, and the
      osteocalcin content of the harvested construct at 4 weeks was also measured.
      RESULTS AND CONCLUSION: All constructs except the hydroxyapatite/P-3 construct
      showed abundant bone formation by histology and both high secretory osteocalcin
      level in the medium and high osteocalcin content after implantation. Our study
      revealed that secretory osteocalcin level in vitro was related to osteocalcin
      content in vivo. The study clearly showed that measuring secretory osteocalcin is
      a nondestructive method of assessing the osteogenic potential of tissue
      engineered bone. One can choose tissue-engineered bone with high osteogenic
      potential by integrating secretory osteocalcin measurement into the process of
      bone-tissue regeneration.

PMID- 21725672
TI  - Influence of radiofrequency ablation of lung cancer on pulmonary function.
AB  - PURPOSE: The purpose of this study was to evaluate altered pulmonary function
      retrospectively after RFA. METHODS: This retrospective study comprised 41
      ablation sessions for 39 patients (22 men and 17 women; mean age, 64.8 years).
      Vital capacity (VC) and forced expiratory volume in 1 s (FEV(1)) at 1 and 3
      months after RFA were compared with the baseline (i.e., values before RFA). To
      evaluate the factors that influenced impaired pulmonary function, univariate
      analysis was performed by using multiple variables. If two or more variables were
      indicated as statistically significant by univariate analysis, these variables
      were subjected to multivariate analysis to identify independent factors. RESULTS:
      The mean VC and FEV(1) before RFA and 1 and 3 months after RFA were 3.04 and 2.24
      l, 2.79 and 2.11 l, and 2.85 and 2.13 l, respectively. The values at 1 and 3
      months were significantly lower than the baseline. Severe pleuritis after RFA was
      identified as the independent factor influencing impaired VC at 1 month (P =
      0.003). For impaired FEV(1) at 1 month, only severe pleuritis (P = 0.01) was
      statistically significant by univariate analysis. At 3 months, severe pleuritis
      (VC, P = 0.019; FEV(1), P = 0.003) and an ablated parenchymal volume >=20 cm(3)
      (VC, P = 0.047; FEV(1), P = 0.038) were independent factors for impaired VC and
      FEV(1). CONCLUSIONS: Pulmonary function decreased after RFA. RFA-induced severe
      pleuritis and ablation of a large volume of marginal parenchyma were associated
      with impaired pulmonary function.

PMID- 21725673
TI  - [Chilaiditi's syndrome complicated by subdiaphragmatic perforated appendicitis:
      unusual manifestation of a rare condition].
AB  - We report on a case of an 80-year-old female patient who presented to the
      emergency room of with right upper quadrant abdominal pain since the day before.
      During the initial diagnostic an abdominal x-ray study revealed an air-filled
      colonic section of the bowel under the right hemidiaphragm corresponding to
      Chilaiditi's sign. The clinical symptoms and laboratory results were mild at this
      time. After 12 h the patient developed right upper quadrant peritonitis due to a
      perforated, subdiaphragmatic appendicitis based on Chilaiditi's syndrome. During
      surgical treatment the cecum and parts of the ascending colon were found to be
      interposed between the liver and right hemidiaphragm. A right hemicolectomy was
      performed which led to complete recovery of the patient. In addition to
      presenting this interesting case this article highlights the regime of the
      diagnostics and therapy of a complication of the very rare condition of
      Chilaiditi's syndrome.

PMID- 21725674
TI  - [Epidural malpositioning of an interscalene plexus catheter].
AB  - A patient received an interscalene plexus catheter before shoulder surgery. After
      induction of general anesthesia catheter placement was performed with Winnie's
      technique and 5 ml of ropivacaine was injected via the catheter. In the recovery
      room slight dyspnea without wheezing was observed which improved spontaneously.
      Following another bolus of ropivacaine, dyspnea and paralysis of the
      contralateral arm developed and the patient became hypotensive. The tomography
      scan showed epidural malpositioning of the catheter. Neuraxial complications of
      interscalene regional anesthesia are especially possible with medially directed
      insertion of the needle and have been described many times in the literature. The
      symptoms and recommendations for prevention are discussed.

PMID- 21725675
TI  - [Bupivacaine toxicity and propofol anesthesia : animal study on intravascular
      bupivacaine injection].
AB  - BACKGROUND: Several reports have confirmed the efficacy of Intralipid(r)
      (containing soya bean oil, egg phospholipids, glycerin and water) in the therapy
      of systemic local anesthetic intoxication. Pretreatment with Intralipid(r)
      shifted the dose-response to bupivacaine-induced asystole in rats. Whether
      intravenous anesthesia with propofol in the widely used medium chain triglyceride
      lipid emulsion increases the therapeutic range of systemically administered
      bupivacaine or not is unknown and was investigated in this study. METHODS: A
      total of 30 piglets aged 2-6 weeks and weighing 4.5-6.5 kg were randomized into 2
      groups and anesthetized with sevoflurane (group S) alone or with propofol 10
      mg/kg body weight (BW)/h plus sevoflurane (group PS). After 60 min of steady
      state anesthesia arterial blood was sampled for assessment of blood gases, acid
      base state and triglyceride plasma concentrations. Thereafter bupivacaine 0.125%
      was continuously infused by an infusion syringe pump through a central venous
      line at a rate of 4 mg/kg BW/min until invasively measured mean arterial pressure
      (MAP) was reduced by 50% of initial value. The bupivacaine infusion was stopped,
      blood for assessment of bupivacaine plasma concentration was drawn and the
      spontaneous hemodynamic course was observed. Resuscitation was not attempted.
      Results are presented as median and range. The Mann-Whitney U-test was used to
      assess differences between the two groups for triglyceride as well as for
      bupivacaine plasma concentrations measured at MAP 50%. A p-value<=0.05 was
      considered to be significant. RESULTS: Baseline conditions (arterial blood pH,
      plasma protein and triglyceride plasma concentrations) did not differ
      significantly between the two groups. After 1 h of anesthesia, triglyceride
      plasma concentrations were significantly increased in group PS (median 0.69
      mmol/l) compared to the corresponding baseline values (median 0.14 mmol/l;
      p<0.001) and to the 1 h values of group S (median 0.16 mmol/l; p<0.001). The
      total amount of bupivacaine administered was 9 mg/kg BW in both groups (6-13
      mg/kg BW in group S, 5-13 mg/kg BW in group PS). Resulting bupivacaine plasma
      concentrations were 180 MUmol/l (83-686 MUmol/l) in group S and 185 MUmol/l (130
      465 MUmol/l) in group PS. However, the total amount of bupivacaine administered
      and bupivacaine plasma concentrations at MAP 50% did not reveal statistically
      significant differences between the two groups but a huge variability of both
      parameters within each group was observed. None of the 30 piglets spontaneously
      recovered and they died from pulseless electrical activity or from asystolic
      cardiac arrest. The time from MAP 50% until cardiac arrest demonstrated a large
      variability but did not reveal significant differences between the two groups.
      The time to cardiac arrest was similar in both groups. CONCLUSION: Medium/long
      chain triglyceride lipid emulsion (50:50) as widely used in propofol solutions
      did not increase therapeutic safety in cases of intravascular bupivacaine
      administration in this piglet model.

PMID- 21725676
TI  - Management of recurrent vault prolapse.
AB  - In the ageing female population, recurrent vaginal vault prolapse is a
      significant healthcare burden. There is limited evidence regarding the optimal
      management strategy for recurrent vault prolapse. This paper aims to discuss
      treatment modalities available for recurrent vault prolapse. A literature search
      and analysis was performed using Medline, PubMed, Cochrane database, current
      texts and references from relevant articles. We found inconclusive evidence
      supporting conservative, mechanical and some surgical options for treating
      recurrent vault prolapse; including iliococcygeal fixation, McCall culdoplasty,
      and infracoccygeal sacropexy. Sacrospinous ligament fixation (SSLF),
      sacrocolpopexy, mesh implants and colpocleisis are shown to have good outcomes in
      Level II studies. Nevertheless, the first two are associated with haemorrhage,
      dyspareunia and scarring whilst colpocleisis is limited to selected patients.
      More well-designed studies are required for recurrent vault prolapse. Current
      evidence suggests SSLF, and sacrocolpopexy are alternative surgical options to
      colpocleisis in treating recurrent vault prolapse. Randomised trials are required
      to determine the efficacy and safety of trocar-guided mesh kits.

PMID- 21725678
TI  - [Correction of adolescent kyphosis. What is the state of the art?].
AB  - Thoracic and thoracolumbar kyphosis is a common deformity in pediatric and
      adolescent populations. Kyphotic deformation of the spine is defined as a curve
      which shows an increase in the dorsal convex angulation. The most common causes
      of kyphosis in pediatric and adolescent populations are Scheuermann's disease,
      postural and congenital kyphosis. The fundamental principles of treatment are
      analysis of the kyphotic deformity and restoration or maintenance of sagittal
      balance. Clinically significant sagittal deformities can lead to severe pain,
      substantial cosmetic alterations, spinal cord dysfunction, problems with
      swallowing, gastrointestinal and cardiopulmonary complications. When the kyphotic
      deformity exceeds a certain point and conservative therapy options are no longer
      sufficient surgical intervention is indicated. The available operative options
      for treatment of the various types of pediatric and adolescent thoracolumbar
      kyphosis include dorsal instrumentation and fusion combined with ventral fusion
      and purely ventral instrumentation and fusion.

PMID- 21725677
TI  - Enhanced survival from CLP-induced sepsis following late administration of low
      doses of anti-IFNgamma F(ab')2 antibody fragments.
AB  - OBJECTIVE: To assess the impact of different doses of anti-interferon gamma (anti
      IFNgamma) F(ab')2 fragments, administered prophylactically, on survival and on
      serum concentration of cytokines in a murine model of sepsis induced by cecal
      ligation and puncture (CLP). We further explore the impact of therapeutic
      administration of the most protective dose on survival. SUBJECTS AND TREATMENT:
      Balb/c mice were prophylactically treated by the intraperitoneal route with anti
      IFNgamma initiated 2 h before CLP and every 24 h for a total of five times in
      each of the following doses: 0.01, 0.1, or 1 mg/kg. Sham and control groups
      received sterile saline solution in a similar scheme. METHODS: Serum tumor
      necrosis factor (TNF), interleukin (IL)-1beta, IL-6, IL-10 and IFNgamma were
      measured at 3, 24 and 48 h after CLP by ELISA. Survival curves were compared
      using a Mantel-Haenzel method. RESULTS: Significant prophylactic protection was
      found only with 0.01 mg/kg, in association with regulation of IL-1beta and IL-10
      concentrations. As therapy, anti-IFNgamma fragments were protective only when
      initiated 24 h after CLP. CONCLUSIONS: Delicate modulation of IFNgamma at the
      correct timing, even when the septic process has begun, is an exciting
      alternative to explore in the treatment of sepsis.

PMID- 21725679
TI  - [Progress in diagnostics is the driving force for developing interventional
      methods].

PMID- 21725680
TI  - Pleasantness of the odor of androstenone as a function of sexual intercourse
      experience in women and men.
AB  - Androstenone (5alpha-androst-16-en-3-one) and other androstenes, body odor
      components occurring in apocrine secretions, may play a role in human
      chemosignaling. We hypothesized that the odor of androstenone may gain hedonic
      value from sexual intercourse experiences via associative learning. Young adults
      (N = 397, 61.5% women, age 21-24 years, randomly sampled regarding sexual
      experience) rated the intensity and pleasantness of the odors of androstenone,
      cinnamon, chocolate, isovaleric acid, lemon, and turpentine. Among women who were
      able to perceive androstenone, the odor was rated as more pleasant (less
      unpleasant) by those who had had experienced sexual intercourse with at least one
      partner (n = 175) than by those who reported never having experienced intercourse
      (n = 12, p = .006). The difference was specific to women. The results suggest
      that, among women, sexual experience may modify the pleasantness of the odor of
      androstenone.

PMID- 21725681
TI  - Vitamin K supplementation increases vitamin K tissue levels but fails to
      counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which
      calcification of connective tissue leads to pathology in skin, eye and blood
      vessels. PXE is caused by mutations in ABCC6. High expression of this transporter
      in the basolateral hepatocyte membrane suggests that it secretes an as-yet
      elusive factor into the circulation which prevents ectopic calcification.
      Utilizing our Abcc6 (-/-) mouse model for PXE, we tested the hypothesis that this
      factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months,
      Abcc6 (-/-) and wild-type mice were put on diets containing either the minimum
      dose of vitamin K required for normal blood coagulation or a dose that was 100
      times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic
      calcification was monitored in vivo by monthly micro-CT scans of the snout, as
      the PXE mouse model develops a characteristic connective tissue mineralization at
      the base of the whiskers. In addition, calcification of kidney arteries was
      measured by histology. Results show that supplemental MK-7 had no effect on
      ectopic calcification in Abcc6 ( -/- ) mice. MK-7 supplementation increased
      vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6 (-/-) mice.
      Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary
      MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but
      failed to counteract ectopic calcification. Hence, we obtained no support for the
      hypothesis that Abcc6 transports vitamin K and that PXE can be cured by
      increasing tissue levels of vitamin K.

PMID- 21725683
TI  - Response to the letter to the editor: Multidisciplinary considerations in the
      implementation of the findings from the American College of Surgeons Oncology
      Group (ACOSOG) Z0011 Study: a practice-changing trial.

PMID- 21725684
TI  - Re: Aggressive surgical approach for patients with T4 gastric carcinoma: promise
      or myth?

PMID- 21725685
TI  - High ligation of inferior mesenteric artery: a standard procedure for colorectal
      cancer?

PMID- 21725686
TI  - Neoadjuvant chemotherapy is associated with improved survival compared with
      adjuvant chemotherapy in patients with triple-negative breast cancer only after
      complete pathologic response.
AB  - INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype of
      breast cancer that is known to be chemosensitive. In patients with TNBC, we
      sought to compare survival outcomes between patients receiving neoadjuvant
      chemotherapy, with and without complete pathologic response (pCR), and those
      receiving adjuvant chemotherapy. METHODS: We performed a retrospective chart
      review and identified 385 patients with stage I-III TNBC who were treated with
      neoadjuvant or adjuvant chemotherapy between 2000 and 2008. Patients were divided
      according to receipt of neoadjuvant chemotherapy with pCR, neoadjuvant
      chemotherapy without pCR, and adjuvant chemotherapy. Data were compared using
      Fisher's exact test and analysis of variance (ANOVA). Kaplan-Meier curves were
      generated. RESULTS: Of 385 patients, 151 (39%) received neoadjuvant chemotherapy
      and 234 (61%) received adjuvant chemotherapy. Twenty-six (17%) of those patients
      receiving neoadjuvant chemotherapy had pCR. After controlling for covariates
      associated with survival in unadjusted tests, patients undergoing neoadjuvant
      chemotherapy with residual tumor had significantly worse survival compared with
      patients receiving adjuvant therapy [hazard ratio (HR) = 0.51, P = 0.007] and a
      trend towards worse survival compared with patients receiving neoadjuvant therapy
      with pCR (HR = 0.19, P = 0.10). CONCLUSIONS: Although previous clinical trials
      have not demonstrated a survival difference between patients receiving
      neoadjuvant versus adjuvant chemotherapy for breast cancer, our study suggests an
      overall survival benefit in patients with pCR following neoadjuvant chemotherapy
      compared with patients receiving adjuvant therapy. It is clear that a prospective
      study needs to be carried out to better elucidate the timing of chemotherapy in
      patients with TNBC.

PMID- 21725687
TI  - Timing of preoperative pharmacoprophylaxis for pancreatic surgery patients: a
      venous thromboembolism reduction initiative.
AB  - BACKGROUND: Venous thromboembolism (VTE) remains a clinical problem in surgical
      oncology. We report the impact of preoperative initiation of subcutaneous heparin
      on VTE events after pancreatic surgery. METHODS: A retrospective cohort study of
      patients undergoing pancreatic surgery by a single surgeon and enrolled in the
      American College of Surgeons National Surgery Quality Improvement Program
      database (FY09/10) was performed. In FY10, a protocol was developed to encourage
      the use of preoperative pharmacoprophylaxis for high-risk patients. We compared
      patient characteristics before and after implementation of the protocol. Our
      primary outcome was 30-day VTE rate and secondary outcomes were bleeding events
      and 30-day mortality. Outcomes were compared by Student's t-test and Fisher's
      exact test. RESULTS: Seventy-three patients were studied, 34 patients underwent
      surgery before and 39 had surgery after implementation of the protocol. All
      patients received intra-operative intermittent compression boots (ICB) and
      postoperative pharmacoprophylaxis. Patients in the two groups were statistically
      equivalent with respect to age, body mass index, procedure length, and VTE risk
      factors. The percentage of patients with a VTE event decreased significantly
      after the protocol (17.6% vs. 2.6%, P=0.035). The mean number of units of red
      blood cells transfused in the OR was not statistically different (0.4 vs. 0.7,
      P=0.43.) Two patients returned to the operating room for bleeding after the
      implementation of the protocol. There were no deaths. CONCLUSIONS: Intraoperative
      ICBs with postoperative initiation of subcutaneous heparin pharmacoprophylaxis
      may be inadequate for VTE prophylaxis for high risk patients. The use of a
      preoperative dose of subcutaneous heparin in high-risk pancreatic surgery
      patients resulted in a statistically significant reduction of VTE events.

PMID- 21725688
TI  - Incorporation of adjuvant therapy into the multimodality management of
      gastrointestinal stromal tumors of the stomach in the United States.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) treatment changed considerably
      with introduction of imatinib in 2001 and reports of early successes. However,
      little is known about imatinib incorporation into practice. Our objective was to
      examine the integration of adjuvant systemic therapy into GIST management.
      METHODS: Patients with gastric GIST were identified (n = 4508) from the National
      Cancer Data Base (2001-2007). Separate regression models were developed to
      examine factors associated with adjuvant and neoadjuvant therapy use. RESULTS: A
      total of 3050 patients underwent surgical resection. From 2001-2003 to 2006-2007,
      use of adjuvant therapy increased from 29 to 47% (P < 0.001). Patients were less
      likely to receive adjuvant therapy if tumors were <3 cm, low grade, had negative
      margins, were treated at low-volume centers, or were diagnosed during 2001-2003
      (P < 0.01). Adjuvant systemic therapy for lesions <3 cm also increased (17 to
      25%, P = 0.001). For high-risk GISTs, adjuvant therapy use increased from 41 to
      58% overall, with increases of 46 to 70% at high-volume centers and 40 to 48% at
      low-volume centers (P < 0.001). Neoadjuvant therapy increased from 0 to 8%;
      patients were more likely to receive neoadjuvant treatment if their tumor was >6
      cm, treated at high-volume centers, or were diagnosed during 2006-2007 (P <
      0.001). CONCLUSIONS: Adjuvant systemic therapy use for GISTs was increasing and
      widespread prior to FDA approval of adjuvant imatinib, suggesting that
      contemporaneous advances in management of advanced GIST were being simultaneously
      and rapidly translated into the adjuvant setting. As relatively costly therapies
      are integrated into practice, more robust tracking systems are needed to monitor
      the incorporation of new treatments.

PMID- 21725691
TI  - A fatal complication of doxylamine in a 1-year-old girl.

PMID- 21725690
TI  - Strong conservation of the bird Z chromosome in reptilian genomes is revealed by
      comparative painting despite 275 million years divergence.
AB  - The divergence of lineages leading to extant squamate reptiles (lizards, snakes,
      and amphisbaenians) and birds occurred about 275 million years ago. Birds, unlike
      squamates, have karyotypes that are typified by the presence of a number of very
      small chromosomes. Hence, a number of chromosome rearrangements might be expected
      between bird and squamate genomes. We used chromosome-specific DNA from flow
      sorted chicken (Gallus gallus) Z sex chromosomes as a probe in cross-species
      hybridization to metaphase spreads of 28 species from 17 families representing
      most main squamate lineages and single species of crocodiles and turtles. In all
      but one case, the Z chromosome was conserved intact despite very ancient
      divergence of sauropsid lineages. Furthermore, the probe painted an autosomal
      region in seven species from our sample with characterized sex chromosomes, and
      this provides evidence against an ancestral avian-like system of sex
      determination in Squamata. The avian Z chromosome synteny is, therefore,
      conserved albeit it is not a sex chromosome in these squamate species.

PMID- 21725692
TI  - Poor correlation between perihematomal MRI hyperintensity and brain swelling
      after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: The perihematomal hyperintensity (PHH) is commonly
      interpreted to represent cerebral edema following intracerebral hemorrhage (ICH),
      but the accuracy of this interpretation is unknown. We therefore investigated the
      relationship between the changes in PHH and the changes in hemispheric brain
      volume as a measure of edema during the first week after ICH. METHODS: Fifteen
      individuals aged 66 +/- 13 with baseline hematoma size of 13.1 ml (range 3-43)
      were prospectively studied with sequential MRI 1.0 +/- 0.5, 2.6 +/- 0.9, and 6.5
      +/- 1.0 days after spontaneous supratentorial ICH. Changes in hemispheric brain
      volume were assessed on MPRAGE using the Brain-Boundary Shift Integral (BBSI).
      Hematoma and PHH volumes were measured on T2-weighted images. RESULTS: Brain
      volume increased a small but statistically significant amount (6.3 +/- 8.0 ml,
      0.6 +/- 0.7%) between the first and second scans relative to 10 normal controls (
      0.9 +/- 4.1 ml, P = 0.02) and returned toward baseline at the third scan (1.5 +/-
      9.5 ml vs. controls 0.9 +/- 4.0 ml, P = 0.85). There were no significant
      differences in the volume changes between the two hemispheres at scan 2 or scan
      3. At both scan 2 (P = 0.04) and scan 3 (P = 0.004), the change in PHH was
      significantly greater than and poorly correlated with the change in ipsilateral
      hemispheric volume. There were no significant correlations between the change in
      NIH Stroke Scale (NIHSS) and the change in PHH, ipsilateral, or total brain
      volume at scan 2 or scan 3 (all P > 0.05). CONCLUSIONS: In patients with small-to
      moderate-sized hematomas, change in PHH was a poor measure of brain edema in the
      first week following ICH. A small degree of bihemispheric brain swelling
      occurred, but was of little clinical significance.

PMID- 21725693
TI  - Agreement in endovascular thrombolysis patient selection based on interpretation
      of presenting CT and CT-P changes in ischemic stroke patients.
AB  - BACKGROUND: To evaluate the agreement in patient selection based on computed
      tomography (CT) and CT-perfusion (CT-P) imaging interpretation between stroke
      specialists in stroke patients considered for endovascular treatment. METHODS:
      All endovascular-treated acute ischemic stroke patients were identified through a
      prospective database from two comprehensive stroke centers; 25 consecutively
      treated patients were used for this analysis. Initial CT images and CT-P data
      were independently interpreted by five board eligible/certified vascular
      neurologists with additional endovascular training to decide whether or not to
      select the patient for endovascular treatment. The CT/CT-P images were evaluated
      separately and used as the sole imaging decision making criteria, 2 weeks apart
      from each other (memory wash-out period). For each set of imaging data inter
      rater and intra-rater agreement scores were obtained using Cohen's kappa
      statistic to assess the proportion of agreement beyond chance. RESULTS: Kappa
      values for the treatment decisions based on CT images was 0.43 (range 0.14-0.8)
      (moderate agreement), and for the decisions based on CTP images was 0.29 (range
      0.07-0.67) (fair agreement) among the five subjects. There was substantial
      variability within the group and between images interpretation. Observed
      agreement on decision to treat with endovascular therapy was found to be 75% with
      CT images and 59% with CT-P images (with no adjustment for chance). Kappa values
      for intra-rater agreement were -0.14 (ranged -0.27-0.27) (poor agreement).
      CONCLUSIONS: There is considerable lack of agreement, even among stroke
      specialists, in selecting acute ischemic stroke patients for endovascular
      treatment based on CT-P changes. This mandates a careful evaluation of CT-P for
      patient selection before widespread adoption.

PMID- 21725694
TI  - Hypertonic saline reduces intracranial hypertension in the presence of high serum
      and cerebrospinal fluid osmolalities.
AB  - BACKGROUND: Osmotherapy has been the cornerstone in the management of patients
      with elevated intracranial pressure (ICP) following traumatic brain injury (TBI).
      Several studies have demonstrated that hypertonic saline (HTS) is a safe and
      effective osmotherapy agent. This study evaluated the effectiveness of HTS in
      reducing intracranial hypertension in the presence of a wide range of serum and
      cerebrospinal fluid (CSF) osmolalities. METHODS: Forty-two doses of 23.4% saline
      boluses for treatment of refractory intracranial hypertension were reviewed
      retrospectively. Thirty milliliters of 23.4% NaCl was infused over 15 min for
      intracranial hypertension, defined as ICP >20 mmHg. The CSF and serum
      osmolalities from frozen stored samples were measured with an osmometer. The
      values of serum sodium, hourly ICP, blood urea nitrogen (BUN), and creatinine
      were obtained directly from the medical records. RESULTS: The serum and CSF
      osmolalities correlated very closely to serum sodium (r > 0.9, P < 0.0001). The
      reduction in ICP from the baseline (measured from either the mean ICP or the
      lowest ICP measurement in the first 6 h after bolus HTS treatment) was
      statistically significant regardless of serum osmolality. The mean reduction from
      baseline to follow-up values was 8.8 mm Hg (P < 0.0001). The decrease in ICP was
      as evident with serum osmolalities >320 as it was at <=320. CONCLUSION: This
      study demonstrates that 23.4% HTS bolus is effective for the reduction of
      elevated ICP in patients with severe TBI even in the presence of high serum and
      CSF osmolalities.

PMID- 21725695
TI  - Instruments measuring spirituality in clinical research: a systematic review.
AB  - INTRODUCTION: Numerous instruments have been developed to assess spirituality and
      measure its association with health outcomes. This study's aims were to identify
      instruments used in clinical research that measure spirituality; to propose a
      classification of these instruments; and to identify those instruments that could
      provide information on the need for spiritual intervention. METHODS: A systematic
      literature search in MEDLINE, CINHAL, PsycINFO, ATLA, and EMBASE databases, using
      the terms "spirituality" and "adult$," and limited to journal articles was
      performed to identify clinical studies that used a spiritual assessment
      instrument. For each instrument identified, measured constructs, intended goals,
      and data on psychometric properties were retrieved. A conceptual and a functional
      classification of instruments were developed. RESULTS: Thirty-five instruments
      were retrieved and classified into measures of general spirituality (N = 22),
      spiritual well-being (N = 5), spiritual coping (N = 4), and spiritual needs (N =
      4) according to the conceptual classification. Instruments most frequently used
      in clinical research were the FACIT-Sp and the Spiritual Well-Being Scale. Data
      on psychometric properties were mostly limited to content validity and inter-item
      reliability. According to the functional classification, 16 instruments were
      identified that included at least one item measuring a current spiritual state,
      but only three of those appeared suitable to address the need for spiritual
      intervention. CONCLUSIONS: Instruments identified in this systematic review
      assess multiple dimensions of spirituality, and the proposed classifications
      should help clinical researchers interested in investigating the complex
      relationship between spirituality and health. Findings underscore the scarcity of
      instruments specifically designed to measure a patient's current spiritual state.
      Moreover, the relatively limited data available on psychometric properties of
      these instruments highlight the need for additional research to determine whether
      they are suitable in identifying the need for spiritual interventions.

PMID- 21725696
TI  - Plastic and reconstructive surgery in Zambia: epidemiology of 16 years of
      practice.
AB  - BACKGROUND: The epidemiology of surgical conditions in developing countries is
      not well studied, but plastic and reconstructive surgery can play a significant
      role in meeting the need for surgical care. Knowledge of the conditions treated
      by a plastic surgeon in a low-income country would inform the development of
      surgical services. METHODS: The surgical log of the lead author from 1993 to 2008
      was reviewed. The cases were performed in 33 surgical facilities in Zambia, and
      name, gender, age, diagnosis, procedure, and hospital were prospectively
      recorded. Data were analyzed for the number and distribution of cases and for
      patterns related to age and gender. RESULTS: Between 1993 and 2008, 5,740
      operations were performed, and complete data were available for 5,735 (99.9%)
      patients. There were 5,774 surgical diagnoses. Of these, 3,885 (67.2%) were
      acquired conditions. These included 1,985 (34.3%) burns, 514 (9.0%) keloids, 448
      (7.8%) nonburn traumas, 410 (7.1%) deep tissue infections, and 343 (5.9%) tumors.
      The 1,889 (32.7%) congenital conditions included 1,322 (22.9%) craniofacial
      defects and 354 (6.1%) limb defects. Children accounted for 78.2% of burns.
      Trauma cases were predominantly male (273, 60.9%). Congenital conditions were
      repaired after 5 years of age in 355 (18.8%) cases. CONCLUSION: Based on a 16
      year case log from one developing country, more than half of conditions related
      to plastic surgery comprised injuries and congenital anomalies. Age- and gender
      related patterns were evident. These findings may inform the provision of
      resources for injury prevention, surgical training, and delivery of surgical
      services.

PMID- 21725697
TI  - Chemical and morphological characterization of aerosol particles at Mt. Krvavec,
      Slovenia, during the Eyjafjallajokull Icelandic volcanic eruption.
AB  - OBJECTIVE: In this work, continuous and size-segregated aerosol measurements at
      Mt. Krvavec, Slovenia, during the Eyjafjallajokull volcanic eruption were
      performed. Based on chemical and morphological characteristics of size-segregated
      particles, the presence of the volcanic aerosols after long-range transport to
      Slovenia was to be confirmed. RESULTS AND CONCLUSIONS: Continuous measurements
      with the aethalometer and SMPS indicated the suspected volcanic ash plume passing
      over the sampling site. The aerosols collected by discrete sampling showed a
      chemical signature similar to the known elemental signature of the Icelandic
      volcanic ash. Coarse particles showed a composition typical for silicates rich in
      metals; in many cases also S was present. Morphological analysis showed particles
      with features indicative of an explosive volcanic eruption, e.g., pumice and
      pumice shards, glass shards, minerals, evidence of steam condensation, etc. The
      high sulfate concentration associated with the fine particles resulted in sulfate
      crystallization within the cascade impactor leading to the formation of large
      structures resembling a "fern". Mass size distributions for Fe, Ti, Mn, Ca, Na,
      and Mg showed one primary peak (for Fe, Mn, and Ti at 2.8 MUm; for Ca, Na, and Mg
      at ca. 4 MUm), which supports the fact that most of the particles in the coarse
      sizes were silicates rich in metals. The size distribution of the water-soluble
      SO(4)(2-) showed a maximum peak at 0.75 MUm, which also confirms the high sulfate
      concentration in the fine particles. Chemical and morphological characterization
      of aerosols collected at Mt. Krvavec indeed confirmed that volcanic ash plume
      passed over Slovenia.

PMID- 21725698
TI  - Combined biological processing and microfiltration in the treatment of unhairing
      wastewater.
AB  - INTRODUCTION: The unhairing step, a part of the beamhouse process, is
      particularly polluting, generating an alkaline wastewater with high
      concentrations of organic and inorganic matter. The aim of this study was to
      evaluate the treatment of this industrial wastewater using a combination of
      biological and microfiltration processes. MATERIALS AND METHODS: The performance
      of the activated sludge system (AS) was evaluated under varying organic loading
      rate (OLR) from 0.9 to 3.4 kg chemical oxygen demand (COD) m(-3) day(-1) and
      decreasing hydraulic retention time (HRT) from 3 to 1.6 days. RESULTS: For an HRT
      of 3 days, the increase of OLR significantly affected the removal of organic
      matter. Therefore, the biological organic matter removal of unhairing wastewater
      decreased from 92% to 66% for COD and from 87 to 53% for biological oxygen demand
      (BOD(5)). GC-MS analyses showed that biological treatment of unhairing wastewater
      contributed to the removal of long chain fatty acids and their degradation
      products. Microfiltration of unhairing wastewater was performed using 0.2 MUm
      pore-size membranes in tangential filtration. The highest removal efficiencies
      were obtained for bacteria (100%) and turbidity (98.4%) which confirmed the
      importance of the microfiltration step in treatment of unhairing wastewater. The
      result showed that the flux decay rate was greatest at the start of the
      microfiltration assay (90 L h(-1) m(2)), becoming 60.7 L h(-1) m(2) after 32 min.
      CONCLUSION: This change indicated that fouling occurred rapidly once the membrane
      module was put into operation.

PMID- 21725699
TI  - Infiltrating hepatocellular carcinoma: seeing the tree through the forest.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related
      death worldwide. It is traditionally difficult to cure, especially when
      discovered at later stages, making early diagnosis and intervention of paramount
      importance. HCC typically arises in the background of chronic liver disease and
      can have various morphologic appearances. One of the most difficult of these to
      recognize on early surveillance imaging is the infiltrative subtype, which can
      account for up to 13% of all HCC cases, and may be more closely associated with
      background hepatitis B infection. DISCUSSION: Certain imaging characteristics can
      provide vital clues, including differing signal intensity on the T1 and T2
      sequences of magnetic resonance imaging (MRI) and the presence/appearance of
      portal vein thrombus. Owing to the diffuse and infiltrating properties of this
      tumor, surgical resection and transplantation are rarely if ever viable
      therapeutic options. Other forms of liver-directed therapy have been attempted
      with limited success, having minimal efficacy and high morbidity. To date, there
      is no data available to determine if the various HCC subtypes respond to systemic
      therapy differently, so this may be the most reasonable approach. Left untreated,
      observed patients commonly progress to hepatic failure fairly rapidly.
      CONCLUSION: Infiltrative HCC can be extremely subtle, and therefore difficult to
      detect, especially in the background of cirrhosis. Providers caring for patients
      with hepatitis, chronic liver disease, and cirrhosis must be extremely vigilant
      in the evaluation of surveillance imaging in order to potentially discover this
      HCC subtype as early as possible and initiate a multidisciplinary treatment plan.

PMID- 21725700
TI  - Comparison of outcomes of laparoscopic versus open appendectomy in adults: data
      from the Nationwide Inpatient Sample (NIS), 2006-2008.
AB  - INTRODUCTION: Although laparoscopic appendectomy (LA) is being performed with
      increased frequency, the utilization of laparoscopy in the management of acute
      appendicitis remains controversial, and it continues to be used selectively.
      OBJECTIVES: This study aims to evaluate outcomes of LA vs. open appendectomy (OA)
      in perforated and non-perforated appendicitis in adults. METHODS: Using the
      Nationwide Inpatient Sample database, clinical data of adults who underwent LA
      and OA for suspected acute appendicitis were evaluated from 2006 to 2008.
      Incidental and elective appendectomies were excluded. RESULTS: A total of 573,244
      adults underwent urgent appendectomy during these 3 years. Overall, 65.2% of all
      appendectomies were performed laparoscopically. Utilization of LA increased 23.7%
      from 58.2% in 2006 to 72.0% in 2008. In acute non-perforated appendicitis, LA had
      a lower overall complication rate (4.13% vs. 6.39%, p < 0.01), lower in-hospital
      mortality (0.03% vs. 0.05%, p < 0.01), and shorter mean length of hospital stay
      (LOS; 1.7 vs. 2.4 days, p < 0.01) compared with OA; however, hospital charges
      were higher in the LA group ($22,948 vs. $20,944, p < 0.01). Similarly, in
      perforated appendicitis, LA was associated with a lower overall complication rate
      (18.75% vs. 26.76%, p < 0.01), lower in-hospital mortality (0.06% vs. 0.31%, p <
      0.01), lower mean hospital charges ($32,487 vs. $38,503, p < 0.01), and shorter
      mean LOS (4.0 vs. 6.0 days, p < 0.01) compared with OA. CONCLUSION: LA is safe
      and associated with lower morbidity, lower mortality, and shorter hospital stay
      with acute perforated and non-perforated appendicitis. Also, in perforated cases,
      LA had an advantage over OA in hospital charges. LA should be considered the
      procedure of choice for perforated and non-perforated appendicitis in adults.

PMID- 21725701
TI  - Pulmonary resection for isolated pancreatic adenocarcinoma metastasis: an
      analysis of outcomes and survival.
AB  - OBJECTIVES: This study was conducted to determine if pulmonary metastasectomy
      (PM) for isolated pancreatic cancer metastases is safe and effective. METHODS:
      This was a retrospective case-control study of patients undergoing PM at our
      institution from 2000 to 2009 for isolated lung metastasis after resection for
      pancreatic cancer. Clinical and pathologic data were compared with a matched
      reference group. Resected neoplasms were immunolabeled for the Dpc4 protein.
      Kaplan-Meier analysis compared overall survival and survival after relapse.
      RESULTS: Of 31 patients with isolated lung metastasis, 9 underwent 10 pulmonary
      resections. At initial pancreas resection, all patients were stage I or II. Other
      baseline characteristics were similar between the two groups. Median time from
      pancreatectomy to PM was 34 months (interquartile range 21-49). During the study,
      29/31(90.6%) patients died. There were no in-hospital mortalities or
      complications after PM. Median cumulative survival was significantly improved in
      the PM group (51 vs. 23 months, p = 0.04). There was a trend toward greater 2
      year survival after relapse in the PM group (40% vs. 27%, p = 0.2). CONCLUSIONS:
      In patients with isolated lung metastasis from pancreatic adenocarcinoma, this is
      the first study to show that pulmonary resection can be performed safely with low
      morbidity and mortality. The improved survival in the PM group may result in part
      from selection bias but may also represent a benefit of the procedure.

PMID- 21725702
TI  - Apelin, diabetes, and obesity.
AB  - Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ.
      Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and
      the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central
      nervous system, particularly in the hypothalamus and in many peripheral tissues.
      Apelin has been shown to be involved in the regulation of cardiovascular and
      fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition
      to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes
      and thus considered as an adipokine. This has opened a new field of investigation
      establishing a link between apelin and metabolic disorders (obesity, type 2
      diabetes, etc.) which is the focus of the present review. Several studies, but
      not all, have reported an increase of plasma apelin concentrations in humans and
      in animal models with different metabolic pathologies. Moreover, important roles
      for apelin both in glucose and lipid metabolism have been highlighted as well as
      the associated signaling pathways. Apelin appears as a beneficial adipokine with
      anti-obesity and anti-diabetic properties and thus as a promising therapeutic
      target in metabolic disorders.

PMID- 21725703
TI  - Endocrine and metabolic aspects of the Wolfram syndrome.
AB  - Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes
      Mellitus, Optic Atrophy and Deafness), is a neurodegenerative disease with
      autosomal recessive inheritance with incomplete penetrance. DIDMOAD is a very
      rare disease with an estimated prevalence of 1 in 770,000 and it is believed to
      occur in 1 of 150 patients with juvenile-onset insulin-dependent diabetes
      mellitus. Additionally, WS may also present with different endocrine and
      metabolic abnormalities such as anterior and posterior pituitary gland
      dysfunction. This mini-review summarizes the variable presentation of WS and the
      need of screening for other metabolic and hormonal abnormalities, coexisting in
      this rare syndrome.

PMID- 21725704
TI  - Association between the T869C polymorphism of transforming growth factor-beta 1
      and diabetic nephropathy: a meta-analysis.
AB  - Accumulating evidence has suggested that transforming growth factor-beta 1 (TGF
      beta1) is a functional candidate for diabetic nephropathy (DN). However,
      association studies investigating the relationship of TGF-beta1 gene T869C
      polymorphism and DN generate inconsistent results. To comprehensively clarify
      this issue, we performed a meta-analysis to evaluate the impact of the
      polymorphism on DN. We searched studies from PubMed and China National Knowledge
      Infrastructure (CNKI) through March 2011. Pooled ORs were calculated under
      allelic/additive/dominant/recessive/over-dominant genetic models. Nine studies
      with 1776 cases and 1740 controls were included. Our results indicated that C
      allele of T869C conferred a significantly increased risk of DN compared with T
      allele (OR = 1.25, 95% CI: 1.05-1.48) for allelic contrast. Similar results were
      also found under additive (OR = 1.57, 95% CI: 1.10-2.23) and dominant (OR = 1.40,
      95% CI: 1.06-1.85) genetic models. However, subgroup analyses stratified by types
      of diabetes showed that significantly increased risks were only observed in type
      2 diabetic patients, and the association persistently existed in further analysis
      for Asian populations. As for type 1 diabetic subjects, no significant
      association was detected under all the genetic models (P > 0.05). Our meta
      analysis suggested that the TGF-beta1 T869C polymorphism conferred an elevated
      risk of DN. However, significant associations were only observed in type 2
      diabetic patients.

PMID- 21725705
TI  - A note on the reproductive performance of Damara, Dorper and Merino sheep under
      optimum management and nutrition for Merino ewes in the eastern wheatbelt of
      Western Australia.
AB  - The reproductive performance of 48 Damara, 42 Dorper and 46 Merino ewes was
      evaluated under an optimum nutritional regime for Merino ewes that included one
      annual joining in a mixed (cropping and sheep) farming system in the eastern
      wheatbelt of Western Australia (W.A.) over a 3-year period. In 2005, when the
      Damara, Dorper and Merino ewes were aged between 8 and 9 months at joining and
      weighed 41.2, 42.4 and 33.3 kg with average body condition scores of 2.3, 2.4 and
      1.8, respectively, their weaning rates were 71% (Damara), 81% (Dorper) and 13%
      (Merino). The Merino ewes had significantly lighter body weights and were lower
      conditioned (p < 0.001) resulting in significantly lower weaning rates (p <
      0.001). In 2006, the Damara, Dorper and Merino ewes weighed 61.9, 69.5 and 61.6
      kg at joining, with body condition scores of 2.8, 3.3 and 2.8, respectively,
      resulting in weaning rates of 52% (Damara), 122% (Dorper) and 117% (Merino).
      While the Damara and Merino weights and body condition scores were not different
      (p > 0.05), the Damara weaning rates were significantly lower compared with the
      Dorper and Merino groups (p < 0.001). The Dorpers were heavier and greater
      conditioned (p < 0.001); however, the weaning rates between the Dorper and Merino
      were not different (p > 0.05). In 2007, the Damara, Dorper and Merino ewes
      weighed 71.6, 77.1 and 70.2 kg at joining with body condition scores of 2.8, 2.8
      and 2.5, respectively. Again, the Dorper ewes were heavier (p < 0.001) than the
      Damaras and Merinos, which were not different (p > 0.05). The Damara and Dorper
      had the same body condition while the Merino ewes were less and different (p <
      0.05). However, there were differences in weaning rates between the three breeds
      (p < 0.001), of 64% (Damara), 105% (Dorper) and 134% (Merino). Over the 3-year
      period, under a nutritional management system optimal for Merino sheep and with
      one annual joining, with increasing age the Merino ewes weaned more lambs.
      However, while the Damara and Dorper ewes conceived and weaned relatively high
      lamb numbers when they were joined as lambs, their reproductive performance
      decreased over time. This nutritional regime resulted in increased levels of
      fatness of the Damara and Dorper ewes with no increase in reproduction rates
      under an annual joining system. A significant factor for the lower conception and
      weaning rates in the Damara ewes was the enlarged fat tail due to the increased
      fat levels, which made it difficult for the rams to impregnate the ewes.

PMID- 21725706
TI  - Integrating multiple cues to depth order at object boundaries.
AB  - We examined the interaction between motion and stereo cues to depth order along
      object boundaries. Relative depth was conveyed by a change in the speed of image
      motion across a boundary (motion parallax), the disappearance of features on a
      surface moving behind an occluding object (motion occlusion), or a difference in
      the stereo disparity of adjacent surfaces. We compared the perceived depth orders
      for different combinations of cues, incorporating conditions with conflicting
      depth orders and conditions with varying reliability of the individual cues. We
      observed large differences in performance between subjects, ranging from those
      whose depth order judgments were driven largely by the stereo disparity cues to
      those whose judgments were dominated by motion occlusion. The relative strength
      of these cues influenced individual subjects' behavior in conditions of cue
      conflict and reduced reliability.

PMID- 21725707
TI  - Quantification of surface amorphous content using dispersive surface energy: the
      concept of effective amorphous surface area.
AB  - We investigate the use of dispersive surface energy in quantifying surface
      amorphous content, and the concept of effective amorphous surface area is
      introduced. An equation is introduced employing the linear combination of surface
      area normalized square root dispersive surface energy terms. This equation is
      effective in generating calibration curves when crystalline and amorphous
      references are used. Inverse gas chromatography is used to generate dispersive
      surface energy values. Two systems are investigated, and in both cases surface
      energy data collected for physical mixture samples comprised of amorphous and
      crystalline references fits the predicted response with good accuracy. Surface
      amorphous content of processed lactose samples is quantified using the
      calibration curve, and interpreted within the context of effective amorphous
      surface area. Data for bulk amorphous content is also utilized to generate a
      thorough picture of how disorder is distributed throughout the particle. An
      approach to quantifying surface amorphous content using dispersive surface energy
      is presented. Quantification is achieved by equating results to an effective
      amorphous surface area based on reference crystalline, and amorphous materials.

PMID- 21725708
TI  - Formulation, characterization, and clinical evaluation of microemulsion
      containing clotrimazole for topical delivery.
AB  - The objective of the present study was to formulate and evaluate microemulsion
      systems for topical delivery of clotrimazole (CTM). The solubility of CTM in
      various oils was determined to select the oil phase of the microemulsion systems.
      Pseudoternary phase diagrams were constructed to identify the area of
      microemulsion existence. Five CTM microemulsion formulations (M1-M5) were
      prepared and evaluated for their thermodynamic stability, pH, refractive index,
      droplet size, viscosity, and in vitro release across cellulose membrane. Among
      the prepared microemulsion formulations, M3 (lemon oil/Tween 80/n-butanol/water)
      and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were
      found to be promising according to their physical properties and CTM cumulative
      percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as
      the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms
      for drug retention in the skin in comparison to the marketed CTM topical cream
      and their stability examined after storage at 40 degrees C for 6 months.
      Microemulsion formulations achieved significantly higher skin retention for CTM
      over the CTM cream. Stability studies showed that M4 preparations were more
      stable than M3. The in vitro anti-fungal activity of M4 against Candida albicans
      was higher than that of the conventional cream. Moreover, clinical evaluation
      proved the efficacy and tolerability of this preparation in the treatment of
      various topical fungal infections.

PMID- 21725709
TI  - A fast method for testing covariates in population PK/PD Models.
AB  - The development of covariate models within the population modeling program like
      NONMEM is generally a time-consuming and non-trivial task. In this study, a fast
      procedure to approximate the change in objective function values of covariate
      parameter models is presented and evaluated. The proposed method is a first-order
      conditional estimation (FOCE)-based linear approximation of the influence of
      covariates on the model predictions. Simulated and real datasets were used to
      compare this method with the conventional nonlinear mixed effect model using both
      first-order (FO) and FOCE approximations. The methods were mainly assessed in
      terms of difference in objective function values (DeltaOFV) between base and
      covariate models. The FOCE linearization was superior to the FO linearization and
      showed a high degree of concordance with corresponding nonlinear models in
      DeltaOFV. The linear and nonlinear FOCE models provided similar coefficient
      estimates and identified the same covariate-parameter relations as statistically
      significant or non-significant for the real and simulated datasets. The time
      required to fit tesaglitazar and docetaxel datasets with 4 and 15 parameter
      covariate relations using the linearization method was 5.1 and 0.5 min compared
      with 152 and 34 h, respectively, with the nonlinear models. The FOCE
      linearization method allows for a fast estimation of covariate-parameter
      relations models with good concordance with the nonlinear models. This allows a
      more efficient model building and may allow the utilization of model building
      techniques that would otherwise be too time-consuming.

PMID- 21725711
TI  - Use of the labour-intensive method in the repair of a rural road serving an
      indigenous community in Jocotan (Guatemala).
AB  - This paper reports the results obtained in an aid project designed to improve
      transport in the municipal area of Jocotan (Guatemala). The rural road network of
      an area occupied by indigenous people was analysed and a road chosen for repair
      using the labour-intensive method-something never done before in this area. The
      manpower required for the project was provided by the population that would
      benefit from the project; the involvement of outside contractors and businesses
      was avoided. All payment for labour went into the pockets of the local people.
      The small earth movements made and the use of local materials guaranteed the
      project's environmental sustainability, while the on-site training of the local
      community prepared its members for the continued maintenance of the road, thus
      investing the project with social sustainability.

PMID- 21725712
TI  - Diffusion tensor imaging evaluation of white matter in adolescents with
      myelomeningocele and Chiari II malformation.
AB  - BACKGROUND: Macrostructural abnormalities in cerebral white matter in patients
      with myelomeningocele are well known, but microstructural abnormalities are not
      as well studied. OBJECTIVE: The aim of this study was to evaluate cerebral white
      matter in adolescents with myelomeningocele using diffusion tensor imaging (DTI),
      and to investigate the effects of ventricular dilation and CSF shunt presence on
      white matter microstructure in these patients. MATERIALS AND METHODS: DTI and T1
      weighted 3-D (T1-3-D) MRI were performed on nine adolescents with
      myelomeningocele and Chiari II malformation and nine age-matched controls. The
      fractional anisotropy (FA) and mean diffusivity (MD) values were measured and
      compared. RESULTS: Significantly decreased FA and increased MD values were
      observed in most white matter regions and fibers in adolescents with
      myelomeningocele compared to controls. Further analysis in patients revealed
      significant changes in DTI parameters in hemispheres with enlarged lateral
      ventricles compared to those with normal ventricle size. In addition, a
      significant difference in FA values in the posterior limb of the internal capsule
      was found in the comparison of hemispheres in patients with or without CSF shunt
      catheters. CONCLUSION: This study revealed widespread microstructural
      abnormalities in white matter in adolescents with myelomeningocele and Chiari II
      malformation. Ventricular dilation may have additional effects on white matter
      microstructure in this patient population. CSF shunt diversion effects on white
      matter may be multifactorial and need further investigation.

PMID- 21725713
TI  - Investigation of schizophrenic patients from Istanbul, Turkey for the presence of
      West Nile virus.
AB  - Association of some neurotropic viruses like Borna Disease virus and Herpes virus
      with schizophrenia is better explained. However, the role of West Nile virus
      (WNV) infection in schizophrenia is not well documented. Therefore, this study
      was performed to investigate possible association between schizophrenia and
      presence of antibodies and WNV RNA in schizophrenic patients. For this, 200 blood
      samples from patients with schizophrenia and 200 from control groups were
      collected in Istanbul, Turkey. WNV RNA was not detected in any of the 200
      patients and 200 controls analyzed by real-time RT-PCR. One hundred and twelve
      sera of schizophrenic patients and 162 of controls were analyzed for the presence
      of IgG antibodies to WNV by a commercial IgG-ELISA (Euroimmun, Germany).
      Antibodies to WNV were detected in 6 schizophrenic patients and 5 controls. ELISA
      positive patients had antipsychotic therapy. The difference between groups in
      terms of seropositivity to WNV was not statistically significant (p = 0.887, p =
      0.148). Known symptoms of schizophrenia were observed in these patients, and
      interestingly majority had close contact to cats in the past and come from
      agricultural area of Turkey where potential area of mosquitoes and bird habitat.
      In conclusion, the results of this study show that antibodies to WNV in people do
      not seem to be associated with schizophrenia. However, detecting antibodies to
      WNV in schizophrenic patients suggests that WNV infection should be considered in
      endemic areas as it may play role in psychiatric diseases.

PMID- 21725714
TI  - Mitochondrial DNA polymorphisms/haplogroups in hereditary spastic paraplegia.
AB  - Mitochondrial dysfunction could contribute to the development of spastic
      paraplegia. Among others, two of the genes implicated in hereditary spastic
      paraplegia encoded mitochondrial proteins and some of the clinical features
      frequently found in these patients resemble those observed in patients with
      mitochondrial DNA (mtDNA) mutations. We investigated the association between
      common mtDNA polymorphisms and spastic paraplegia. The ten mtDNA polymorphisms
      that defined the common European haplogroups were determined in 424 patients, 19%
      with a complicated phenotype. A rare haplogroup was associated with the disease
      in patients without a SPG3A, SPG4, or SPG7 mutation. Allele 10398G was more
      frequent among patients with a pure versus complicated phenotype. This mtDNA
      polymorphism was previously associated with the risk of developing other
      neurodegenerative diseases. In conclusion, some mtDNA polymorphisms could
      contribute to the development of spastic paraplegia or act as modifiers of the
      phenotype.

PMID- 21725715
TI  - Late marginal ulcers after gastric bypass for morbid obesity. Clinical and
      endoscopic findings and response to treatment.
AB  - Marginal ulcer (MU) is an occasional complication after gastric bypass which can
      occur early or late after surgery. In this study, we evaluated the incidence,
      clinical presentation, and endoscopic behavior of patients with late MU. Five
      hundred fifty morbidly obese patients were evaluated prospectively performing an
      endoscopic study 1-8 years after surgery. They were submitted either to
      laparotomic (n = 392) or laparoscopic (n = 158) approach. Six patients (1%)
      presented late MU 12 to 84 months after surgery. Four patients had single ulcer,
      while two patients had multiple ulcers. All were treated with proton pump
      inhibitors (PPIs). Several endoscopic evaluations were performed in each patient
      showing healing and no recurrence of the ulcer. Late MU occurs in a small
      proportion (1%) of patients submitted to gastric bypass. It can be single or
      multiple. Medical treatment with PPIs achieves healing at a mean time of 7
      months. Several endoscopic evaluations should be performed in these patients in
      order to demonstrate healing of the ulcer and no recurrence.

PMID- 21725716
TI  - Characteristics of eyes with secondary loss of visual acuity receiving variable
      dosing ranibizumab for neovascular age-related macular degeneration.
AB  - PURPOSE: The aim of this work is to investigate the characteristics of eyes
      failing to maintain visual acuity (VA) receiving variable dosing ranibizumab for
      neovascular age-related macular degeneration (nAMD) after three initial loading
      doses. METHODS: A consecutive series of patients with nAMD, who, after three
      loading doses of intravitreal ranibizumab (0.5 mg each), were re-treated for
      fluid seen on optical coherence tomography. After exclusion of eyes with previous
      treatment, follow-up less than 12 months, or missed visits, 99 patients were
      included in the analysis. The influence of baseline characteristics, initial VA
      response, and central retinal thickness (CRT) fluctuations on the VA stability
      from month 3 to month 24 were analyzed using subgroups and multiple regression
      analyses. RESULTS: Mean follow-up duration was 21.3 months (range 12-40 months,
      32 patients followed-up for >=24 months). Secondary loss of VA (loss of five
      letters or more) after month 3 was seen in 30 patients (mean VA improvement from
      baseline +5.8 letters at month 3, mean loss from baseline -5.3 letters at month
      12 and -9.7 at final visit up to month 24), while 69 patients maintained vision
      (mean gain +8.9 letters at month 3, +10.4 letters at month 12, and +12.8 letters
      at final visit up to month 24). Secondary loss of VA was associated with the
      presence of pigment epithelial detachment (PED) at baseline (p 0.01), but not
      with baseline fibrosis/atrophy/hemorrhage, CRT fluctuations, or initial VA
      response. Chart analysis revealed additional individual explanations for the
      secondary loss of VA, including retinal pigment epithelial tears, progressive
      fibrosis, and atrophy. CONCLUSIONS: Tissue damage due to degeneration of PED,
      retinal pigment epithelial tears, progressive fibrosis, progressive atrophy, or
      massive hemorrhage, appears to be relevant in causing secondary loss of VA
      despite vascular endothelial growth factor suppression. PED at baseline may
      represent a risk factor.

PMID- 21725717
TI  - Preferred use of the ipsilateral pedicled TRAM flap for immediate breast
      reconstruction: an illustrated approach.
AB  - BACKGROUND: Recent experience with the ipsilateral TRAM flap has shown that it
      has the advantage of a longer functional pedicle length, which allows tension
      free inset of well-vascularized tissue into the breast pocket. This leads to
      better positioning and shaping of the reconstructed breast with minimal
      disruption of the inframammary fold. The purpose of this article was to provide
      an illustrated approach to the ipsilateral TRAM flap and to clarify the technique
      when applied in the context of immediate breast reconstruction following cancer
      extirpation. METHODS: A prospective evaluation of 89 patients who underwent
      immediate breast reconstruction following skin-sparing mastectomy for breast
      cancer was performed. All patients underwent ipsilateral TRAM reconstruction. The
      innate insetting advantage of the ipsilateral TRAM flap is illustrated in the
      article. The key steps of the technique were as follows: (1) The ipsilateral
      corner of the flap was used as the axillary tail, leaving the more bulky part to
      form the main body of the breast; (2) To avoid undesirable twists, a right TRAM
      was rotated clockwise so that its apex points superiorly; (3) This flap was
      subsequently tunneled into the breast pocket while preserving the inframammary
      fold. The opposite maneuvers were done for the left side; (4) If the flap was
      congested, venous augmentation was performed where the tributary of the axillary
      vein or the thoracodorsal vein was anastomosed with the inferior epigastric vein
      from the flap with an interposed vein graft (17% of cases). RESULTS: All flaps
      survived and flap-related complications included partial necrosis of tissue
      across the midline (2.2%), palpable fat necrosis (22%), and hematoma requiring
      drainage (2.2%). All flaps were raised concurrent with the resection, and the
      combined operative time ranged from 3.5 to 6 h, with a mean hospital stay of 7
      days. CONCLUSION: The ipsilateral TRAM flap was a reliable flap with low
      complication rates and short surgery time. It was our preferred choice for
      pedicled breast reconstruction in all cases, except for the ptotic breast or if
      abdominal scarring excludes its use.

PMID- 21725718
TI  - Mammaplasties and medicolegal issues: 50 cases of litigation in aesthetic surgery
      of the breast.
AB  - BACKGROUND: Aesthetic surgery procedures are increasing all over the world, and
      so are related medicolegal questions and litigation cases. Aesthetic
      mammaplasties represent a very important part of this field and consequently many
      cases of error appear. Most of these errors lead to litigation from which plastic
      surgeons rarely can be exonerated. The aim of this article was to evaluate
      different errors ascribed to the plastic surgeon, the rate of cases in which
      professional responsibility has been identified, and the type of guilt imputed.
      METHODS: Each case is based on the evaluation of both documentation used by the
      judge and the relationships of two specialists involved in the assessment of the
      presumed error. In every case, problems complained about by the patient and the
      eventually related error of the surgeon were analyzed. Moreover, the eventual
      identification of professional responsibility, the quantified damage, and its
      possible reduction by another corrective operation were considered. RESULTS: The
      cases studied (N=50) were divided into 34 cases of augmentation mammaplasty, 11
      cases of reduction mammaplasty, and 5 cases of mastopexy. Most of the problems
      complained about by patients were in the preoperative and intraoperative phases.
      In only 10% of the cases was the informed consent contested and an expected
      reduction of the damage was individuated in less than half of cases. CONCLUSIONS:
      The evaluation of aesthetic damage is a tricky question due to different aspects
      such as the psychological component or the frequent lack of adequate photographic
      documentation of the patient before the operation. Moreover, whenever possible
      reduction of the damage is proposed, the patient's willingness to undergo another
      operation, with all its related costs and benefits, must be considered.

PMID- 21725719
TI  - BACE1 elevation is involved in amyloid plaque development in the triple
      transgenic model of Alzheimer's disease: differential Abeta antibody labeling of
      early-onset axon terminal pathology.
AB  - beta-amyloid precursor protein (APP) and presenilins mutations cause early-onset
      familial Alzheimer's disease (FAD). Some FAD-based mouse models produce amyloid
      plaques, others do not. beta-Amyloid (Abeta) deposition can manifest as compact
      and diffuse plaques; it is unclear why the same Abeta molecules aggregate in
      different patterns. Is there a basic cellular process governing Abeta plaque
      pathogenesis? We showed in some FAD mouse models that compact plaque formation is
      associated with a progressive axonal pathology inherent with increased expression
      of beta-secretase (BACE1), the enzyme initiating the amyloidogenic processing of
      APP. A monoclonal Abeta antibody, 3D6, visualized distinct axon terminal labeling
      before plaque onset. The present study was set to understand BACE1 and axonal
      changes relative to diffuse plaque development and to further characterize the
      novel axonal Abeta antibody immunoreactivity (IR), using triple transgenic AD
      (3xTg-AD) mice as experimental model. Diffuse-like plaques existed in the
      forebrain in aged transgenics and were regionally associated with increased BACE1
      labeled swollen/sprouting axon terminals. Increased BACE1/3D6 IR at axon
      terminals occurred in young animals before plaque onset. These axonal elements
      were also co-labeled by other antibodies targeting the N-terminal and mid-region
      of Abeta domain and the C-terminal of APP, but not co-labeled by antibodies
      against the Abeta C-terminal and APP N-terminal. The results suggest that
      amyloidogenic axonal pathology precedes diffuse plaque formation in the 3xTg-AD
      mice, and that the early-onset axonal Abeta antibody IR in transgenic models of
      AD might relate to a cross-reactivity of putative APP beta-carboxyl terminal
      fragments.

PMID- 21725720
TI  - Applied behavior analysis programs for autism: sibling psychosocial adjustment
      during and following intervention use.
AB  - Psychosocial adjustment in siblings of children with autism whose families were
      using a home-based, applied behavior analysis (ABA) program was compared to that
      of siblings in families who were not using any intensive autism intervention.
      Data gathered from parents, siblings and teachers indicated that siblings in ABA
      families experienced neither significant drawbacks nor benefits in terms of their
      behavioral adjustment, sibling relationship quality and self-concept compared to
      control group siblings, either during or following intervention use. Parents and
      siblings perceived improvements in sibling interaction since the outset of ABA,
      with parents somewhat more positive in their views than were siblings. Social
      support was associated with better sibling outcomes in all groups. Implications
      for supporting families using ABA are considered.

PMID- 21725721
TI  - Rituximab in chronic lymphocytic leukemia.
AB  - Rituximab (Rituxan; iogen Idec, San Diego, CA, USA) is a human-mouse chimeric
      monoclonal antibody specific for CD20, a surface glycoprotein expressed on B
      lymphocytes. Administration of rituximab as a single agent to patients with
      chronic lymphocytic leukemia (CLL) has limited clinical activity, but generally
      does not eradicate leukemia from the marrow. However, when administered in
      combination with chemotherapy, rituximab can improve the survival of patients
      relative to those treated with chemotherapy alone. As a result of this, the US
      Food and Drug Administration approved the use of rituximab in previously
      untreated and previously treated CD20-positive CLL in combination with
      fludarabine monophosphate and cyclophosphamide. The results of clinical studies
      evaluating the activity of rituximab when used alone or in combination with other
      antileukemia agents for the treatment of this disease are reviewed here.

PMID- 21725723
TI  - History of preclinical models of intracerebral hemorrhage.
AB  - In order to understand a disease process, effective modeling is required that can
      assist scientists in understanding the pathophysiological processes that take
      place. Intracerebral hemorrhage (ICH), a devastating disease representing 15% of
      all stroke cases, is just one example of how scientists have developed models
      that can effectively mimic human clinical scenarios. Currently there are three
      models of hematoma injections that are being used to induce an ICH in subjects.
      They include the microballoon model introduced in 1987 by Dr. David Mendelow, the
      bacterial collagenase injection model introduced in 1990 by Dr. Gary Rosenberg,
      and the autologous blood injection model introduced by Dr. Guo-Yuan Yang in 1994.
      These models have been applied on various animal models beginning in 1963 with
      canines, followed by rats and rabbits in 1982, pigs in 1996, and mice just
      recently in 2003. In this review, we will explore in detail the various injection
      models and animal subjects that have been used to study the ICH process while
      comparing and analyzing the benefits and disadvantages of each.

PMID- 21725724
TI  - Comparison of different preclinical models of intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is the most devastating type of stroke. It is
      characterized by spontaneous bleeding in brain parenchyma and is associated with
      a high rate of morbidity and mortality. Presently, there is neither an effective
      therapy to increase survival after intracerebral hemorrhage nor a treatment to
      improve the quality of life for survivors. A reproducible animal model of
      spontaneous ICH mimicking the development of acute and delayed brain injury after
      ICH is an invaluable tool for improving our understanding of the underlying
      mechanisms of ICH-induced brain injury and evaluating potential therapeutic
      interventions. A number of models have been developed. While different species
      have been studied, rodents have become the most popular and widely utilized
      animals used in ICH research. The most often used methods for experimental
      induction of ICH are injection of bacterial collagenase and direct injection of
      blood into the brain parenchyma. The "balloon" method has also been used to mimic
      ICH for study. In this summary, we intend to provide a comparative overview of
      the technical methods, aspects, and pathologic findings of these types of ICH
      models. We will also focus on the similarities and differences among these rodent
      models, achievements in technical aspects of the ICH model, and discuss important
      aspects in selecting relevant models for study.

PMID- 21725725
TI  - Cerebral amyloid angiopathy-related microhemorrhages in Alzheimer's disease: a
      review of investigative animal models.
AB  - There is a growing understanding of cerebral amyloid angiopathy (CAA), which
      accounts for the majority of primary lobal intracerebral hemorrhages (ICH) among
      the elderly [1] and is cited as the cause of 20% of spontaneous ICHs in patients
      over 70 years of age [2]. The basis for this disease process is the deposition
      and formation of eventually destructive amyloid plaques in the walls of brain
      vessels, predominantly arterial but not excluding venules and capillaries [3].
      Investigation of the pathophysiology and therapies for CAA-associated hemorrhages
      have been made possible through animal models utilizing species that develop CAA
      in a similar fashion to humans, such as the squirrel monkey, rhesus monkey, dog
      and mutant and transgenic mouse strains, which exhibit the age-related
      development of amyloid plaques, progressive neurodegeneration and CAA-associated
      hemorrhages. The disease course in these animal models resembles that seen in the
      clinical setting for patients with CAA. Rodent studies have been able to
      demonstrate the strong role of CAA and CAA-associated microhemorrhages in the
      pathogenesis and progression of CAA with and without AD [4]. This review will
      present the existing understanding of CAA-associated microhemorrhages frequently
      observed in AD, different animal models, involved imaging and the role of animal
      models in the development of therapeutics including immunotherapies such as anti
      Abeta antibodies for the treatment of CAA and its associated microhemorrhages.

PMID- 21725726
TI  - Multiparametric characterisation of the perihemorrhagic zone in a porcine model
      of lobar ICH.
AB  - OBJECTIVES: To describe early perihemorrhagic changes after lobar intracerebral
      hemorrhage (ICH) using multiparametric neuromonitoring [intracranial pressure
      (ICP), cerebral blood flow (CBF), tissue oxygenation (PbrO2), microdialysis
      (MD)]. METHODS: Seven anaesthetized male swine were examined over 12 h. Four
      cerebral probes were inserted around the ICH (ICP, MD, CBF and PbrO2). A right
      frontal autologous arterial ICH (1.5 mL) was induced in all animals. RESULTS:
      Initial ICH creation was hampered by using a soft 22-G cannula. A modified
      injection technique with a 90 degrees  bent steel cannula (20 G) allowed for an
      87.5% success rate in ICH formation. After induction of ICH, ICP significantly
      increased from 2 mmHg to 9 mmHg. No significant PbrO2 or CBF reduction occurred
      during the monitoring period. Consequently, microdialysis did not indicate
      overall mean deterioration in the hematoma group over time. The indicator of
      ischemia (extracellular lactate) did not increase significantly during the
      monitoring period. Individual monitoring episodes demonstrated hypoxic episodes
      with consecutive metabolic derangement. These effects were reversible by
      optimizing CPP and FiO2. CONCLUSION: We established a reproducible cortical ICH
      model using multiparametric neuromonitoring. Subtle changes in ICP were observed.
      No evidence for the existence of a perihemorrhagic ischemic area was found,
      hypothetically because of the small hematoma size. Individual animals underwent
      critical PbrO2 and CBF decreases with consecutive metabolic derangement. The
      effect of larger hematoma volumes should be evaluated with this setup in future
      studies to study volume-dependent deterioration.

PMID- 21725727
TI  - Developing a model of chronic subdural hematoma.
AB  - Chronic subdural hematoma (CSDH) is a common neurosurgical condition that has a
      high incidence in the increasing elderly population of many countries.
      Pathologically, it is defined as a persistent liquefied hematoma in the subdural
      space more than 3 weeks old that is generally encased by a membraneous capsule.
      CSDHs likely originate after minor head trauma, with a key factor in its
      development being the potential for a subdural cavity to permit its expansion
      within, which is usually due to craniocerebral disproportion. The pathogenesis of
      CSDH has been attributed to osmotic or oncotic pressure differences, although
      measurements of these factors in the CSDH fluid do not support this theory.
      Current belief is that CSDH arises from recurrent bleeding in the subdural space,
      caused by a cycle of local angiogenesis, inflammation, coagulation and ongoing
      fibrinolysis. However, because of a lack of detailed knowledge about the precise
      mechanisms, treatment is often limited to surgical interventions that are
      invasive and often prone to recurrence. Thus, it is possible that an easily
      reproducible and representative animal model of CSDH would facilitate research in
      the pathogenesis of CSDH and aid with development of treatment options.

PMID- 21725728
TI  - A mouse model of intracranial aneurysm: technical considerations.
AB  - Intracranial aneurysms can be induced by a single stereotaxic injection of
      elastase into the cerebrospinal fluid at the right basal cistern in hypertensive
      mice. This mouse model produces large aneurysm formations with an incidence of 60
      80% within 3-4 weeks. Intracranial aneurysms in this model recapitulate key
      pathological features of human intracranial aneurysms. Several technical factors
      are critical for the successful induction of intracranial aneurysms in this
      model. Precise stereotaxic placement of the needle tip into the cerebrospinal
      fluid space is especially important. Aneurysm formations in this model can serve
      as a simple and easily interpretable outcome for future studies that utilize
      various inhibitors, knockout mice, or transgenic mice to test roles of specific
      molecules and pathways in the pathophysiology of intracranial aneurysms.

PMID- 21725729
TI  - The postpartum period of pregnancy worsens brain injury and functional outcome
      after cerebellar hemorrhage in rats.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is one of the most common causes of
      maternal deaths related to the postpartum period. This is a devastating form of
      stroke for which there is no available treatment. Although premenopausal females
      tend to have better outcomes after most forms of brain injury, the effects of
      pregnancy and child birth lead to wide maternal physiological changes that may
      predispose the mother to an increased risk for stroke and greater initial injury.
      METHODS: Three different doses of collagenase were used to generate models of
      mild, moderate and severe cerebellar hemorrhage in postpartum female and male
      control rats. Brain water, blood-brain barrier rupture, hematoma size and
      neurological evaluations were performed 24 h later. RESULTS: Postpartum female
      rats had worsened brain water, blood-brain barrier rupture, hematoma size and
      neurological evaluations compared to their male counterparts. CONCLUSION: The
      postpartum state reverses the cytoprotective effects commonly associated with the
      hormonal neuroprotection of (premenopausal) female gender, and leads to greater
      initial injury and worsened neurological function after cerebellar hemorrhage.
      This experimental model can be used for the study of future treatment strategies
      after postpartum brain hemorrhage, to gain a better understanding of the
      mechanistic basis for stroke in this important patient subpopulation.

PMID- 21725730
TI  - Hyperglycemia and hemorrhagic transformation of cerebral infarction: a
      macroscopic hemorrhagic transformation rat model.
AB  - The recombinant tissue plasminogen activator (t-PA) is a useful therapy for acute
      ischemic stroke patients, but there is a major risk factor of hemorrhagic
      transformation. Hyperglycemic patients are not able to admit t-PA because
      hyperglycemia exaggerates ischemic brain and vascular damage following transient
      focal cerebral ischemia and frequently induces hemorrhagic transformation of the
      infarct during reperfusion. However, the mechanisms underlying hemorrhagic
      transformation induced by hyperglycemia are still unknown. Furthermore, previous
      reports focused upon microscopic hemorrhage rather than macroscopic hemorrhagic
      transformation. In order to make these problems clear, it is necessary to
      establish an experimental model that induces constant macroscopic hemorrhagic
      transformation in the infarct area caused by middle cerebral artery occlusion and
      the reperfusion model on the hyperglycemic rat. This experimental study can
      establish the model in which macroscopic hemorrhagic transformation occurs
      following 1.5 h occlusion and 24 h reperfusion by using the intraluminal thread
      method on hyperglycemic rats. It might be useful to determine the mechanisms and
      understand why hyperglycemia exaggerates the causes inducing macroscopic
      hemorrhagic transformation in the infarct area, and this reproducible model
      provides a platform for evaluating treatment strategies.

PMID- 21725731
TI  - Hemorrhagic transformation induced by acute hyperglycemia in a rat model of
      transient focal ischemia.
AB  - Hemorrhagic transformation (HT) is a major factor limiting the use of tissue
      plasminogen activator for stroke. HT has been found in animals undergoing
      transient focal cerebral ischemia with hyperglycemia. This study examined the
      incidence rate, location and content of HT.Rats were divided into two groups: the
      hyperglycemic group and normoglycemic group. Rats received an injection of 50%
      glucose (6 ml/kg, i.p.) or an equivalent volume of saline 15 min before 2-h
      transient middle cerebral artery occlusion (tMCAO) with reperfusion. Rats were
      killed 4, 8 or 24 h later and used for blood-brain barrier permeability,
      hemoglobin content, brain edema, and infarct volume measurements. Mortality and
      HT incidence rates were also evaluated. We found that all hyperglycemic rats had
      HT, and two out of six normoglycemic rats had HT 24 h after tMCAO. Hyperglycemic
      rats had more severe Evans blue leakage (p<0.05) and brain edema (p<0.05) in the
      ipsilateral hemisphere. However, infarct volumes were the same in hyperglycemic
      and normoglycemic rats. In conclusion, acute hyperglycemia reliably and
      consistently resulted in hemorrhagic transformation in a rat model of transient
      focal cerebral ischemia. The model is useful for experimental assessment of new
      therapies for HT.

PMID- 21725732
TI  - A novel preclinical model of germinal matrix hemorrhage using neonatal rats.
AB  - BACKGROUND: Germinal matrix hemorrhage (GMH) is a neurological disorder
      associated with very low birth weight premature infants. This event can lead to
      post-hemorrhagic hydrocephalus, cerebral palsy, and mental retardation. This
      study developed a novel animal model for pre-clinical investigations. METHODS:
      Neonatal rats underwent infusion of clostridial collagenase into the right
      germinal matrix (anterior caudate) region using stereotaxic techniques.
      Developmental milestones were evaluated over 10 days, cognitive function at 3
      weeks, and sensorimotor function at 4 weeks after collagenase infusion. This was
      accomplished by anthropometric quantifications of cranial, cerebral, cardiac, and
      splenic growths. RESULTS: Collagenase infusion led to delays in neonatal
      developmental milestones, followed by cognitive and sensorimotor dysfunctions in
      the juvenile animals. Cranial growth was accelerated during the first week after
      injury, and this was followed by significant brain atrophy, splenomegaly, and
      cardiac hypertrophy 3 weeks later. CONCLUSION: This study characterized the
      developmental delays, mental retardation, and cerebral palsy features resembling
      the long-term clinical course after germinal matrix hemorrhage in premature
      infants. Pre-clinical testing of therapeutics in this experimental model could
      lead to improved patient outcomes while expanding upon the pathophysiological
      understanding of this disease.

PMID- 21725734
TI  - Clot formation, vascular repair and hematoma resolution after ICH, a coordinating
      role for thrombin?
AB  - Following intracerebral hemorrhage (ICH) there is a sequential response involving
      activation of the coagulation cascade/platelet plug formation, vascular repair,
      upregulation of endogenous defense mechanisms and clot resolution. How these
      responses are coordinated and modified by different hematoma sizes has received
      little attention. This paper reviews evidence that thrombin can modulate and may
      coordinate the components of the endogenous response. This has potential
      consequences for treatment of ICH with a number of modalities.

PMID- 21725733
TI  - Intracranial hemorrhage: mechanisms of secondary brain injury.
AB  - ICH is a disease with high rates of mortality and morbidity, with a substantial
      public health impact. Spontaneous ICH (sICH) has been extensively studied, and a
      large body of data has been accumulated on its pathophysiology. However, the
      literature on traumatic ICH (tICH) is limited, and further investigations of this
      important topic are needed. This review will highlight some of the cellular
      pathways in ICH with an emphasis on the mechanisms of secondary injury due to
      heme toxicity and to events in the coagulation process that are common to both
      sICH and tICH.

PMID- 21725735
TI  - The dual role of SRC kinases in intracerebral hemorrhage.
AB  - Src kinase signaling has been implicated in multiple mechanisms of intracerebral
      hemorrhage (ICH). These include (1) thrombin-mediated mitogenic stress, (2)
      excitatory amino acid (AA)-mediated excitatory toxicity, (3) vascular endothelial
      growth factor (VEGF) and matrix metalloproteinases (MMPs)-mediated changes of
      vascular permeability, (4) cytokines-mediated inflammatory responses, and (5)
      others. These work together after ICH, causing brain injuries in the acute stage
      and self-repair in the recovery stage. We found that acute administration of the
      Src inhibitor, PP2, blocks the blood-brain barrier (BBB) breakdown and brain
      edema that occurs after ICH. However, delayed and chronic administration of PP2
      prevents the BBB repair and edema resolution after ICH. These results led us to
      suggest that the two contradictory findings share the same principles at least in
      part via activation of Src kinases in acute or recovery stages after ICH. Acute
      Src kinase activation after ICH leads to BBB damage, and chronic Src kinase
      activation after ICH leads to BBB repair.

PMID- 21725736
TI  - Brain arteriovenous malformation pathogenesis: a response-to-injury paradigm.
AB  - Brain arteriovenous malformations (AVMs) are a rare but important cause of
      intracranial hemorrhage (ICH) in young adults. In this paper, we review both
      human and animal studies of brain AVM, focusing on the: (1) natural history of
      AVM hemorrhage, (2) genetic and expression studies of AVM susceptibility and
      hemorrhage, and (3) strategies for development of a brain AVM model in adult
      mice. These data target various mechanisms that must act in concert to regulate
      normal angiogenic response to injury. Based on the various lines of evidence
      reviewed in this paper, we propose a "response-to-injury" model of brain AVM
      pathogenesis.

PMID- 21725737
TI  - The evolving landscape of neuroinflammation after neonatal hypoxia-ischemia.
AB  - Hypoxic-ischemic brain injury remains a leading cause of mortality and morbidity
      in neonates. The inflammatory response, which is characterized in part by
      activation of local immune cells, has been implicated as a core component for the
      progression of damage to the immature brain following hypoxia-ischemia (HI).
      However, mounting evidence implicates circulating immune cells recruited to the
      site of damage as orchestrators of neuron-glial interactions and perpetuators of
      secondary brain injury. This suggests that re-directing our attention from the
      local inflammatory response toward the molecular mediators believed to link brain
      immune cell interactions may be a more effective approach to mitigating the
      inflammatory sequelae of perinatal HI. In this review, we focus our attention on
      cyclooxygenase-2, a mediator by which peripheral immune cells may modulate
      signaling pathways in the brain that lead to a worsened outcome. Additionally, we
      present an overview of emerging therapeutic modalities that target mechanisms of
      neuroinflammation in the hypoxic-ischemic neonate.

PMID- 21725738
TI  - Red blood cell lysis and brain tissue-type transglutaminase upregulation in a
      hippocampal model of intracerebral hemorrhage.
AB  - Red blood cell (RBC) lysis and iron release contribute to intracerebral
      hemorrhage (ICH)-induced brain injury. Tissue-type transglutaminase (tTG), which
      has a role in neurodegeneration, is upregulated after ICH. The current study
      investigated the effect of RBC lysis and iron release on brain tTG levels and
      neuronal death in a rat model of ICH. This study had three parts: (1) Male
      Sprague-Dawley rats received an intrahippocampal injection of 10 MUL of either
      packed RBCs or lysed RBCs; (2) rats had a 10 MUL injection of either saline,
      hemoglobin or FeCl2; (3) rats received a 10 MUL injection of hemoglobin and were
      treated with an iron chelator, deferoxamine or vehicle. All rats were killed 24 h
      later, and the brains were sectioned for tTG and Fluoro-Jade C staining. Lysed
      but not packed RBCs caused marked tTG upregulation (p<0.05) and neuronal death
      (p<0.05) in the ipsilateral hippocampus CA-1 region. Both hemoglobin and iron
      mimicked the effects of lysed RBCs, resulting in tTG expression and neuronal
      death (p<0.05). Hemoglobin-induced tTG upreglution and neuronal death were
      reduced by deferoxamine (p<0.05). These results indicate that RBC lysis and iron
      toxicity contribute to neurodegeneration after ICH.

PMID- 21725739
TI  - Cytoprotective role of haptoglobin in brain after experimental intracerebral
      hemorrhage.
AB  - After intracerebral hemorrhage (ICH), hemoglobin (Hb) that is released from
      erythrocytes within the brain hematoma is highly cytotoxic and leads to severe
      brain edema and direct neuronal damage. Therefore, neutralization of Hb could
      represent an important target for reducing the secondary injury after ICH.
      Haptoglobin (Hp), an endogenous Hb-binding protein in blood plasma, is found in
      this study to be upregulated in the hematoma-affected brain after ICH. Both in
      vivo and in vitro studies indicate that Hp upregulation is primarily mediated by
      oligodendrocytes. Hp acts as a secretory protein capable of neutralizing the cell
      free Hb. We also found in an "ICH-like" injury that Hp-KO mice show the most
      severe brain injury and neurological deficits, whereas Hp-Tg mice are the most
      resistant to ICH injury, suggesting that a higher Hp level is associated with the
      increased resistance of animals to hemolytic product-mediated brain injury after
      ICH. We conclude that brain-derived Hp plays a cytoprotective role after ICH, and
      Hp may represent a new potential therapeutic target for management of ICH.

PMID- 21725740
TI  - Effects of aging on autophagy after experimental intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) causes severe brain injury in aged rats. Autophagy
      occurs in the brain after ICH, and the present study examined the effects of
      aging on autophagy after ICH. Aged (18-22-month) and young (4-6-month) male
      Fischer rats received an intracerebral injection of 100-MUL autologous whole
      blood. Rats were killed at day 7 for Western blot analysis to measure microtubule
      associated protein light chain-3 (LC3), a biomarker of autophagosome, and
      cathepsin D, a lysosomal biomarker. Rats were killed at 11 weeks after ICH for
      brain histology. Age-related changes in neurological deficits were also examined.
      Western blotting showed that the LC3-I/LC3-II conversion ratio in the ipsilateral
      basal ganglia was higher in aged compared to young rats (p<0.05). Perihematomal
      cathepsin D levels were also higher in aged rats (p<0.05). Neurological deficits
      after ICH were more severe in aged rats, and they had a slower recovery of
      function (p<0.05). In addition, there were more ferritin and OX-42 positive cells
      in the ipsilateral basal ganglia in aged than in young rats 11 weeks after ICH
      (p<0.05). Brain atrophy was found in both young and aged rats. In conclusion, ICH
      causes more severe autophagy and neurological deficits in aged rats.

PMID- 21725741
TI  - Effects of gender on heart injury after intracerebral hemorrhage in rats.
AB  - Intracerebral hemorrhage (ICH)-induced brain injury is less in female than in
      male rats, and estrogen can reduce such injury in males. Myocardial injury occurs
      after ischemic and hemorrhagic stroke, and the current study investigated the
      effects of gender on heart injury after ICH in rats. In the first part of the
      study, male and female rats had an intracerebral injection of 100 MUL autologous
      blood, and sham-operated rats had a needle insertion. In the second part of the
      study, male rats were treated with 17beta-estrodiol or vehicle 2 h after ICH. All
      rats were then killed after 3 days and heart samples collected for histology and
      Western blot analysis. ICH caused heart injury, including petechial hemorrhage in
      male and female rats. To quantify heart stress following ICH, heat shock proteins
      (HSP) 32 and 27 were measured by Western blot analysis. We found that heart HSP
      32 levels were higher in female compared to male rats after ICH (p<0.01), but
      there was no effect of gender in sham-operated rats (p>0.05), nor were there
      gender differences in myocardial HSP27 levels. Treatment with 17beta-estrodiol
      increased HSP-32 levels in male ICH rats (p<0.05). In conclusion, an ICH results
      in heart injury by an unknown mechanism. Gender and estrogen affect the heart
      response to ICH.

PMID- 21725742
TI  - Iron accumulation and DNA damage in a pig model of intracerebral hemorrhage.
AB  - Cerebral iron overload causes brain injury after intracerebral hemorrhage (ICH)
      in rats and pigs. The current study examined whether an iron chelator,
      deferoxamine, can reduce ICH-induced DNA damage in pigs. Pigs received an
      injection of autologous blood into the right frontal lobe. Deferoxamine (50
      mg/kg, i.m.) or vehicle was given 2 h after ICH and then every 12 h up to 7 days.
      Animals were killed at day 3 or day 7 after ICH to examine iron accumulation and
      DNA damage. We found that ICH resulted in the development of a reddish
      perihematomal zone, with iron accumulation and DNA damage within that zone.
      Deferoxamine treatment reduced the perihematomal reddish zone, and the number of
      Perls' (p<0.01) and TUNEL (p<0.01) positive cells. In conclusion, iron
      accumulates in the perihematomal zone and causes DNA damage. Systemic
      deferoxamine treatment reduces ICH-induced iron overload and DNA damage in pigs.

PMID- 21725743
TI  - Subarachnoid hemorrhage causes pulmonary endothelial cell apoptosis and
      neurogenic pulmonary edema in mice.
AB  - OBJECTS: Neurogenic pulmonary edema (NPE) is a well-known complication of
      subarachnoid hemorrhage (SAH), which potentially causes a poor outcome. The aim
      of this study was to examine if NPE occurs in the endovascular perforation model
      of SAH in mice and if apoptosis contributes to NPE development after SAH in mice.
      METHODS: Sham-operated or SAH mice were treated with an intraperitoneal
      administration of vehicle or an antiapoptotic drug Z-Val-Ala-Asp
      fluoromethylketone (Z-VAD-FMK) 1 h post-SAH. Pulmonary edema measurements and
      evaluation of apoptosis occurrence were performed on the lung at 24 h post-SAH.
      RESULTS: SAH caused NPE, which was associated with apoptosis of pulmonary
      endothelial cells. Z-VAD-FMK significantly prevented apoptosis and NPE.
      CONCLUSIONS: Pulmonary endothelial cell apoptosis contributes to the
      pathophysiology of NPE after SAH in mice.

PMID- 21725744
TI  - Hemoglobin expression in neurons and glia after intracerebral hemorrhage.
AB  - The purpose of this study was to examine the expression of hemoglobin (Hb) in the
      brain after intracerebral hemorrhage (ICH) and the effects of hemin and iron on
      neuronal Hb. For the in vivo studies, male Sprague-Dawley rats received either a
      sham operation or an ICH. The rats were killed 1, 4, 24 or 72 h later, and brains
      were used for real-time polymerase chain reaction (PCR) and immunohistochemistry.
      For the in vitro study, primary cultured neurons were exposed to either hemin or
      vehicle. Some neurons also received treatment with deferoxamine, an iron
      chelator. Neurons were collected 24 h later for real-time PCR. We found that
      alpha-globin (HbA) and beta-globin (HbB) mRNA levels in the ipsilateral basal
      ganglia are significantly increased after ICH, and Hb is localized in neurons and
      glia cells. Exposure of neurons to hemin also upregulated HbA and HbB mRNA
      levels. Hemin-induced HbA and HbB expression in cultured neurons was reduced by
      deferoxamine treatment. These results indicate that ICH increases HbA and HbB
      expression in neurons and glia cells, and that heme and iron may be important
      factors in inducing endogenous Hb expression after ICH.

PMID- 21725745
TI  - Isoflurane preconditioning affords functional neuroprotection in a murine model
      of intracerebral hemorrhage.
AB  - INTRODUCTION: Exposure to isoflurane gas prior to neurological injury, known as
      anesthetic preconditioning, has been shown to provide neuroprotective benefits in
      animal models of ischemic stroke. Given the common mediators of cellular injury
      in ischemic and hemorrhagic stroke, we hypothesize that isoflurane
      preconditioning will provide neurological protection in intracerebral hemorrhage
      (ICH). METHODS: 24 h prior to intracerebral hemorrhage, C57BL/6J mice were
      preconditioned with a 4-h exposure to 1% isoflurane gas or room air.
      Intracerebral hemorrhage was performed using a double infusion of 30-MUL
      autologous whole blood. Neurological function was evaluated at 24, 48 and 72 h
      using the 28-point test. Mice were sacrificed at 72 h, and brain edema was
      measured. RESULTS: Mice preconditioned with isoflurane performed better than
      control mice on 28-point testing at 24 h, but not at 48 or 72 h. There was no
      significant difference in ipsilateral hemispheric edema between mice
      preconditioned with isoflurane and control mice. CONCLUSION: These results
      demonstrate the early functional neuroprotective effects of anesthetic
      preconditioning in ICH and suggest that methods of preconditioning that afford
      protection in ischemia may also provide protection in ICH.

PMID- 21725746
TI  - The neuroprotective effects of cyclooxygenase-2 inhibition in a mouse model of
      aneurysmal subarachnoid hemorrhage.
AB  - The CNS inflammatory reaction occurring after aneurysmal subarachnoid hemorrhage
      (SAH) involves the upregulation of numerous cytokines and prostaglandins.
      Cyclooxygenase (COX) inhibition is a well-established pharmacological anti
      inflammatory agent. Previous studies have shown marked increases in COX-2
      expression in neurons, astrocytes, microglia, and endothelial cells following
      brain injury. COX-2 inhibition has been shown to be beneficial following various
      types of brain injury. This experiment investigates the role of COX-2 activity in
      early brain injury following SAH. CD-1 mice were subjected to an endovascular
      perforation model of SAH or SHAM surgery. Following experimental SAH animals were
      treated with the specific COX-2 inhibitor, NS398, in dosages of either 10 or 30
      mg/kg. Neurological performance and brain edema were evaluated 24 and 72 h after
      SAH. NS398 at 30 mg/kg significantly reduced SAH-induced neurological
      deterioration. NS 398 at 30 mg/kg resulted in a trend toward the reduction of SAH
      induced cerebral edema. Treatment had no effect on mortality. This experiment
      provides preliminary evidence that COX-2 inhibition is an effective
      pharmacological intervention for the prevention of brain edema and the
      preservation of neurological function following SAH.

PMID- 21725747
TI  - Sonic hedgehog agonist fails to induce neural stem cell precursors in a porcine
      model of experimental intracranial hemorrhage.
AB  - BACKGROUND: The role of endogenous neural stem cell progenitors in recovery from
      intracranial hemorrhage remains to be elucidated. Proliferation of such stem
      cells in the subventricular zone has been described in rodent models of
      experimental intracranial hemorrhage. Administration of a sonic hedgehog agonist
      at the time of hemorrhage was hypothesized to increase the quantity of such
      precursor cells. METHODS: Two groups of pigs were subjected to injection of
      autologous blood into the right frontal lobe. One group was also injected at the
      same site with a sonic hedgehog agonist at the time of the hemorrhage to
      stimulate cell growth, and the other was given a vehicle control. The pigs
      received intravenous BrdU for 5 days postoperatively to label replicating cells,
      and then were sacrificed at intervals up to 21 days. RESULTS: Pigs in the
      hemorrhage only group demonstrated increased and more persistent BrdU staining in
      the subventricular zone relative to pigs in the group that received sonic
      hedgehog agonist. The latter group demonstrated increased BrdU activity in non
      neural lineage cells in the area of the hemorrhage. CONCLUSION: Sonic hedgehog
      agonist did not induce subventricular zone neural stem cell progenitor division
      after experimental intracranial hemorrhage in a pig model.

PMID- 21725748
TI  - NC1900, an arginine vasopressin analogue, fails to reduce brain edema and improve
      neurobehavioral deficits in an intracerebral hemorrhagic stroke mice model.
AB  - OBJECTIVE: There is mounting evidence suggesting that arginine vasopressin via
      its V1a receptor interaction is involved in the regulation of the brain water
      channel, aquaporin-4 (AQP4). The role of AQP4 in brain edema resolution has been
      thoroughly investigated in knock-out animal studies, which showed that its
      depletion increases brain water content in models of vasogenic edema. As a
      result, we tested the hypothesis that the activation of V1a receptor by it
      selective agonist will decrease brain edema in a mouse intracerebral hemorrhage
      (ICH) model. MATERIALS AND METHODS: ICH was induced by injection of bacterial
      collagenase into the right basal ganglia in CD1 male mice (weight 30-35 g). The
      animals were divided into the following groups: sham, ICH+vehicle, and ICH+AVP
      V1a receptor agonist. Brain edema and neurological outcomes were evaluated at 24
      and 72 h post-ICH. RESULTS: We found that collagenase injection increased brain
      edema and resulted in subsequent neurobehavioral deficits at both time points.
      Treatment with our agonist had no effect on the ICH outcomes at both time points.
      CONCLUSIONS: Our results suggest that the activation of the V1a receptor has no
      beneficial effect on secondary brain injury following ICH in mice.

PMID- 21725749
TI  - Geldanamycin reduced brain injury in mouse model of intracerebral hemorrhage.
AB  - We investigated the effect of the heat shock protein inducer geldanamycin on the
      development of secondary brain injury after ICH in mice. The effect of the drug
      at two different concentrations was evaluated at two time points: 24 and 72 h
      after ICH induction. In the first part of this study, a total of 30 male CD-1
      mice were randomly divided into four groups: one sham group and three ICH groups.
      ICH animals received either an intraperitoneal injection of vehicle or
      geldanamycin (1 or 10 mg/kg). Neurological deficits and brain water content were
      evaluated 24 h after ICH. In the second part of this study, the effect of a high
      concentration of geldanamycin was evaluated 72 h after ICH. Neurological deficits
      were evaluated by the Garcia neuroscoring, wire hanging and beam balance tests.
      For estimation of brain water content, the "wet/dry weight" method was used. We
      demonstrated that administration of geldanamycin (10 mg/kg) ameliorated ICH
      induced increase of brain water content significantly in both parts of the study.
      Geldanamycin improved the neurological outcome according to performance on Garcia
      and beam balance tests in the 72 h part of this study. Geldanamycin-induced
      induction of heat shock protein after ICH has a neuroprotective effect and may be
      a therapeutic target for ICH.

PMID- 21725750
TI  - Combined systemic thrombolysis with alteplase and early hyperbaric oxygen therapy
      in experimental embolic stroke in rats: relationship to functional outcome and
      reduction of structural damage.
AB  - INTRODUCTION: The only causal therapy in ischemic stroke is thrombolysis with
      recombinant tissue plasminogen activator (rtPA), but it is feasible only for few
      patients, and new therapies are needed. This study investigates the effects of
      systemic thrombolysis with rtPA combined with hyperbaric oxygen therapy (HBOT) in
      embolic stroke in rats. METHODS: In 22 male Wistar rats, an embolic ischemic
      stroke was induced. The animals were randomized to one of four groups: control,
      thrombolysis alone, HBOT sequential or HBOT parallel with thrombolysis. HBOT (2.4
      ATA, 1 h) started 45 min (sequential) or 120 min (parallel) after stroke. rtPA
      was given intravenously 120 min after stroke onset. Functional tests were
      performed after stroke induction and after treatment. After 6 h infarct volume
      and intracerebral hemorrhagic complications were assessed. RESULTS: Compared to
      the control group only the combination of HBOT and thrombolysis significantly
      improved the functional outcome (p=0.03) and reduced the infarct volume (p=0.01),
      whereas thrombolysis alone did not show a significant benefit. In all treatment
      groups there was a trend towards fewer hemorrhagic transformations. CONCLUSION:
      Hyperbaric oxygen in combination with thrombolysis shows neuroprotection in acute
      ischemic stroke in rats by reducing infarct volume and improving functional
      outcome in the early poststroke period.

PMID- 21725751
TI  - Neutrophil depletion diminishes monocyte infiltration and improves functional
      outcome after experimental intracerebral hemorrhage.
AB  - Inflammation contributes to secondary injury and neuronal loss after
      intracerebral hemorrhage, but the role of individual immune populations in these
      processes is unclear. In a mouse model, the injection of autologous blood into
      the striatum was associated with an intense inflammatory cell infiltrate composed
      of neutrophils, monocytes, and dendritic cells. Selective depletion of
      neutrophils resulted in decreased infiltration of monocytes and improved
      functional outcomes at day 3 post-hemorrhage. These findings indicate that
      neutrophil infiltration into the site of hemorrhage contributes to brain injury
      either by direct cellular damage or the recruitment of monocytes.

PMID- 21725752
TI  - Hydrogen inhalation is neuroprotective and improves functional outcomes in mice
      after intracerebral hemorrhage.
AB  - OBJECTIVE: Oxidative stress contributes significantly to the development of
      secondary brain injury after intracerebral hemorrhage (ICH). It has been
      previously demonstrated that hydrogen gas can decrease oxidative stress by
      scavenging reactive oxygen species. We hypothesized that hydrogen therapy will
      reduce brain oxidative stress in mice after ICH and thereby will lead to reduced
      brain edema and improved neurological outcomes. MATERIALS AND METHODS: CD1 male
      mice (weight 30-35 g) were divided into the following groups: sham, ICH+vehicle
      (room air), ICH+1-h hydrogen treatment, and ICH+2-h hydrogen treatment. ICH was
      induced by injection of bacterial collagenase into the right basal ganglia. The
      evaluation of outcomes was done at two time points: 24 and 72 h post-ICH. Brain
      water content was measured for assessment of brain edema (wet/dry weight method),
      and three neurological tests were performed pre- and postoperatively. RESULTS:
      Collagenase injection was found to induce brain edema and impair functional
      performance of rats. The hydrogen inhalation reduced these effects acutely (24
      h); however it exhibited only a tendency to improvement in the delayed study (72
      h). CONCLUSIONS: Our results suggest that hydrogen inhalation exerts an acute
      brain-protective effect in the mouse ICH model. However, the acute hydrogen
      therapy alone is not sufficient to improve delayed ICH outcomes in this model.

PMID- 21725753
TI  - Deferoxamine reduces cavity size in the brain after intracerebral hemorrhage in
      aged rats.
AB  - This study investigated whether deferoxamine (DFX), an iron chelator, reduces
      cavity size after ICH in aged rats. Aged male Fischer rats (18 months old) had an
      intracaudate injection of 100 MUL autologous blood and were treated with DFX or
      vehicle. Rats were euthanized at day 56 and brains were perfused for histology
      and immunohistochemistry. Hematoxylin and eosin staining was used to examine
      hematoma cavity presence and size. Immunohistochemistry was performed to measure
      the number of cells positive for ferritin, heme oxygenase-1 (HO-1), glial
      fibrillary acidic protein (GFAP) and OX-6. Neurological deficits were also
      examined. In aged rats with ICH, a cavity formed in the caudate in 7 out of 12
      vehicle-treated rats and 1 out of 9 DFX-treated rats. DFX treatment significantly
      reduced the size of the ICH-induced cavity (p<0.05) as well as neurological
      deficits (p<0.05). DFX also reduced the number of ferritin (p<0.05) and HO-1
      (p<0.01) positive cells in the ipsilateral basal ganglia. However, DFX had no
      effect on brain GFAP and OX-6 immunoreactivity 2 months after ICH.In conclusion,
      DFX reduces cavity size, neurological deficits, and immunoreactivity for ferritin
      and HO-1 after ICH in aged rats, supporting the suggestion that DFX may reduce
      brain injury in ICH patients.

PMID- 21725754
TI  - Post-treatment with SR49059 improves outcomes following an intracerebral
      hemorrhagic stroke in mice.
AB  - Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by
      severe brain edema formation leading to cerebral blood flow compromise and
      parenchymal damage. Arginine vasopressin (AVP), a non-peptide antidiuretic
      hormone, has recently been implicated as a modulator of brain edema following
      injury. In this study, we investigated the effects of SR49059, a highly specific
      AVP V1a receptor antagonist, on brain injury outcomes following ICH, specifically
      assessing the ability of SR49059 in reducing brain edema and improving
      neurobehavioral deficits. Male CD1 mice (n=35) were randomly assigned to the
      following groups: sham, ICH, ICH with SR49059 at 0.5 mg/kg, and ICH with SR49059
      at 2 mg/kg. ICH was induced by using the collagenase injection model, and
      treatment was given 1 h after surgery. Post-assessment was conducted at 24 and 72
      h after surgery, and included brain water content and neurobehavioral testing.
      The study found that SR49059 significantly reduced cerebral edema at 24 and 72 h
      post-ICH injury and improved neurobehavioral deficits at 72 h. Our study suggests
      that blockage of the AVP V1a receptor is a promising treatment target for
      improving ICH-induced brain injury. Further studies will be needed to confirm
      this relationship and determine future clinical direction.

PMID- 21725755
TI  - Deferoxamine affects heat shock protein expression in heart after intracerebral
      hemorrhage in aged rats.
AB  - Cardiac dysfunction can occur after intracerebral hemorrhage (ICH). This study
      examined the expression of heat shock proteins (HSPs) in the heart after ICH in
      aged rats and whether deferoxamine (DFX), an iron chelator, affects HSP
      expression. Male Fischer 344 rats (18 months old) received an injection of 100
      MUl autologous blood into the right caudate, whereas sham-operated rats had a
      needle insertion. The rats were treated with DFX or vehicle at 2 and 6 h after
      ICH and then every 12 h for 3 days. Rats were killed 3 days after ICH, and the
      hearts were sampled for Western blot analysis of HSP-27 and HSP-32. Western
      blotting showed that levels of HSP-32 were reduced in the heart after ICH
      (p<0.05), and this reduction was normalized by DFX (p<0.05). DFX had no effects
      on heart HSP-32 levels in sham-operated rats. ICH also resulted in a reduction in
      HSP-27 (p<0.05), but DFX treatment reduced HSP-27 further (p<0.05). In addition,
      DFX reduced HSP-27 levels in sham rats. In conclusion, ICH causes HSP-27 and -32
      reductions in the heart of aged rats. Deferoxamine treatment has different
      effects on the expression of HSP-27 and HSP-32.

PMID- 21725756
TI  - Neuroprotection by melatonin after germinal matrix hemorrhage in neonatal rats.
AB  - BACKGROUND: Germinal matrix hemorrhage (GMH) is a devastating neurological
      disorder of very low birth weight premature infants that leads to post
      hemorrhagic hydrocephalus, cerebral palsy, and mental retardation. Melatonin is a
      potent antioxidant known to reverse free-radical mediated injury in the brain.
      This study investigated the effect of melatonin treatment after GMH injury.
      METHODS: Clostridial collagenase was infused into the right germinal matrix
      region of neonatal rats with stereotaxic technique. Cognitive function,
      sensorimotor ability, cerebral, cardiac and splenic growths were measured in
      juvenile animals. RESULTS: Systemic melatonin treatment ameliorated cognitive and
      sensorimotor dysfunction at the juvenile developmental stage. This hormone also
      normalized brain atrophy, splenomegaly, and cardiac hypertrophy consequences at 1
      month after injury. CONCLUSION: This study supports the role of free radicals in
      acute neonatal hemorrhagic brain injury. Melatonin is an effective antioxidant
      that can protect the infant's brain from the post-hemorrhagic consequences of
      mental retardation and cerebral palsy. Further mechanistic studies are warranted
      to determine the mechanisms behind these neuroprotective effects.

PMID- 21725757
TI  - Endothelin receptor-A (ETa) inhibition fails to improve neonatal hypoxic-ischemic
      brain injury in rats.
AB  - Cerebral hypoxia-ischemia (HI) is an important cause of mortality and disability
      in newborns. It is a result of insufficient oxygen and glucose circulation to the
      brain, initiating long-term cerebral damage and cell death. Emerging evidence
      suggests that endothelin receptor-A (ETA) activation can play an important role
      in mediating brain damage. In this study, we investigated the role of ETA
      receptor inhibition using ABT-627 in neonatal HI injured rats. Postnatal day 10
      Sprague-Dawley rat pups (n=91) were assigned to the following groups: sham
      (n=28), HI (vehicle, n=32), and HI with ABT-627 at 3 mg/kg (n=31). The Rice
      Vannucci model was used to induce ischemia by ligating the right common carotid
      artery, followed by a 2 h hypoxic episode using 8% oxygen in a 37 degrees C
      chamber. Postoperative assessment was conducted at 48 h after injury and again at
      4 weeks. At the acute time point, investigative markers included cerebral edema,
      infarction volume, and body weight change. Neurobehavioral testing was measured
      at 4 weeks post-injury. Our findings indicated that ABT-627 had no effect on the
      measured parameters. This study suggests that ETA receptor blockade using ABT-627
      post-treatment fails to improve neurological outcomes in neonatal HI injured
      rats.

PMID- 21725758
TI  - FTY720 is neuroprotective and improves functional outcomes after intracerebral
      hemorrhage in mice.
AB  - Intracerebral hemorrhage (ICH) accounts for 20% of all strokes and is the most
      devastating form across all stroke types. Lymphocytes have been shown to
      potentiate cerebral inflammation and brain injury after stroke. FTY720
      (Fingolimod) is an immune-modulating drug that prevents the egress of peripheral
      lymphocytes from peripheral stores. We hypothesized that FTY720 would reduce
      peripheral circulating lymphocytes, resulting in reduced brain injury and
      improved functional outcomes. CD-1 mice were anesthetized and then injected with
      collagenase into the right basal ganglia. Animals were divided into three groups:
      sham, ICH+Vehicle, and ICH+FTY720, by the intra-peritoneal route at 1 h after ICH
      induction. Brain water content was measured at 24 and 72 h. Neurobehavioral tests
      included corner test, forelimb use asymmetry, paw placement, wire-hang test, beam
      balance test, and a Neuroscore. FTY720 significantly reduced brain edema and
      improved neurological function at all time points tested. Lymphocyte modulation
      with FTY720 is an effective neuroprotective strategy to reduce brain injury and
      promote functional recovery after ICH.

PMID- 21725759
TI  - Thrombin preconditioning reduces iron-induced brain swelling and brain atrophy.
AB  - Cerebral preconditioning with a low dose of thrombin attenuates brain edema
      induced by intracerebral hemorrhage (ICH), a large dose of thrombin or iron. This
      study examined whether or not thrombin preconditioning (TPC) reduces neuronal
      death and brain atrophy caused by iron. The right hippocampus of rats was
      pretreated with or without thrombin, and iron was then injected into the same
      location 3 days later. Rats were killed at 1 day or 7 days after iron injection,
      and the brains were used for histology. We found that TPC reduced neuronal death
      and brain swelling in the hippocampus 1 day after iron injection, and hippocampal
      atrophy 7 days later. Western blots showed that thrombin activates p44/42 mitogen
      activated protein kinase (p44/42 MAPK) and 70-kDa ribosomal protein S6 kinase
      (p70 S6K). Our results indicate that TPC reduction of iron-induced neuronal death
      may be through the p44/42 MAPK /p70 S6K signal transduction pathway.

PMID- 21725760
TI  - Capsaicin pre-treatment provides neurovascular protection against neonatal
      hypoxic-ischemic brain injury in rats.
AB  - Capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, has
      recently been shown to provide neuroprotection against brain injury in
      experimental adult models of cerebral ischemia. Accordingly, in this study, we
      investigated the way in which capsaicin-mediated TRPV1 modulation could attenuate
      damage in an experimental hypoxic-ischemic (HI) neonatal brain injury model. The
      Rice-Vannucci method was used in 10-day-old rat pups by performing unilateral
      carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37 degrees C).
      Capsaicin was administered intraperitoneally (0.2 mg/kg or 2.0 mg/kg) at 3 h pre
      HI or 1 h post-HI. Post assessment included measurement of infarction volume at
      24 and 72 h in addition to an assessment of the vascular dynamics of the middle
      cerebral artery (MCA) at 6 h post-HI. The results indicated that pre-treatment
      with capsaicin reduced infarction volume significantly with either low-dose or
      high-dose treatment. Pre-treatment also improved myogenic tone and decreased
      apoptotic changes in the distal MCA. We concluded that capsaicin pre-treatment
      may provide neurovascular protection against neonatal HI.

PMID- 21725761
TI  - Effects of recombinant osteopontin on blood-brain barrier disruption after
      subarachnoid hemorrhage in rats.
AB  - OBJECTS: We determined effects of recombinant OPN (r-OPN), a pleiotropic
      extracellular matrix protein, on blood-brain barrier (BBB) disruption and matrix
      metalloproteinase (MMP)-9 activation after subarachnoid hemorrhage (SAH) in rats.
      METHODS: The endovascular perforation model of SAH was used. SAH or sham-operated
      rats were treated with pre-SAH intracerebroventricular administration of two
      dosages of r-OPN, r-OPN+GRGDSP (an L-arginyl-glycyl-L-aspartate-dependent
      integrin receptor antagonist), albumin or vehicle. Neurological impairments,
      brain edema and BBB disruption were evaluated, and Western blot analyses were
      performed in the brain at 24 h after SAH. RESULTS: r-OPN significantly prevented
      brain edema and BBB disruption compared with the control rats, associated with
      the suppression of nuclear factor-kappaB and mitogen-activated protein kinase
      pathways, leading to MMP-9 inactivation. These effects were blocked by GRGDSP.
      CONCLUSIONS: L-arginyl-glycyl-L-aspartate-dependent integrin receptor-mediated
      multiple signaling pathways may be involved in the protective effects of r-OPN
      against BBB disruption after SAH.

PMID- 21725762
TI  - Protective effect of hydrogen gas therapy after germinal matrix hemorrhage in
      neonatal rats.
AB  - BACKGROUND: Germinal matrix hemorrhage (GMH) is a neurological disease of very
      low birth weight premature infants leading to post-hemorrhagic hydrocephalus,
      cerebral palsy, and mental retardation. Hydrogen (H2) is a potent antioxidant
      shown to selectively reverse cytotoxic oxygen-radical injury in the brain. This
      study investigated the therapeutic effect of hydrogen gas after neonatal GMH
      injury. METHODS: Neonatal rats underwent stereotaxic infusion of clostridial
      collagenase into the right germinal matrix brain region. Cognitive function was
      assessed at 3 weeks, and then sensorimotor function, cerebral, cardiac and
      splenic growths were measured 1 week thereafter. RESULTS: Hydrogen gas inhalation
      markedly suppressed mental retardation and cerebral palsy outcomes in rats at the
      juvenile developmental stage. The administration of H2 gas, early after neonatal
      GMH, also normalized the brain atrophy, splenomegaly and cardiac hypertrophy 1
      month after injury. CONCLUSION: This study supports the role of cytotoxic oxygen
      radical injury in early neonatal GMH. Hydrogen gas inhalation is an effective
      strategy to help protect the infant brain from the post-hemorrhagic consequences
      of brain atrophy, mental retardation and cerebral palsy. Further studies are
      necessary to determine the mechanistic basis of these protective effects.

PMID- 21725763
TI  - Pretreatment with normobaric and hyperbaric oxygenation worsens cerebral edema
      and neurologic outcomes in a murine model of surgically induced brain injury.
AB  - BACKGROUND: Hyperbaric oxygenation is a readily available treatment modality, and
      its ability to improve neurological outcomes in a variety of animal models has
      been demonstrated. This study was designed to investigate the use of a single
      pretreatment regimen of either hyperbaric oxygenation or normobaric oxygenation
      to determine its effects in a murine model of surgically induced brain injury
      (SBI). MATERIALS AND METHODS: Hyperbaric oxygen (2.5ATM, 1 h), normobaric oxygen
      (100% FIO2, 1 h) or room air (21% FIO2, 1 h) was applied on CD-1 mice
      immediately, or at 1, 2 or 3 h followed by SBI or sham surgical operation.
      Neurological assessment of the animals was done by a blinded observer at 24 and
      72 h using a 21-point modified Garcia scale, wire hanging test, and beam balance
      test. The brain edema was evaluated using brain water content at 24 and 72 h
      after SBI. RESULTS: There was no statistically significant difference in the
      mortality rate after treatment compared with the SBI group. The brain water
      content after SBI was significantly increased in the right (ipsilateral) frontal
      lobe surrounding the site of surgical resection compared with the sham group.
      Both hyperbaric and normobaric oxygen treatment significantly increased the brain
      edema and worsened the neurological outcomes using a 21-point Garcia score
      compared with the SBI group. The brain edema at 24 h after injury was most
      pronounced in the group treated with normobaric oxygenation 2 h prior to surgery.
      These differences disappeared at 72 h after SBI. CONCLUSION: Immediate
      pretreatment with either hyperbaric (2.5ATM, 1 h) or normobaric oxygen (100%
      FIO2, 1 h) increased brain edema and worsened neurological function at 24 h
      following SBI.

PMID- 21725764
TI  - Beneficial effect of hyperbaric oxygenation after neonatal germinal matrix
      hemorrhage.
AB  - BACKGROUND: Germinal matrix hemorrhage (GMH) is a potentially devastating
      neurological disease of very low birth weight premature infants. This leads to
      post-hemorrhagic hydrocephalus, cerebral palsy, and mental retardation.
      Hyperbaric oxygen (HBO) treatment is a broad neuroprotectant after brain injury.
      This study investigated the therapeutic effect of HBO after neonatal GMH.
      METHODS: Neonatal rats underwent stereotaxic infusion of clostridial collagenase
      into the right germinal matrix (anterior caudate) brain region. Cognitive
      function was assessed at 3 weeks, and then sensorimotor, cerebral, cardiac, and
      splenic growths were measured 1 week thereafter. RESULTS: Hyperbaric oxygen (HBO)
      treatment markedly improved upon the mental retardation and cerebral palsy
      outcome measurements in rats at the juvenile developmental stage. The
      administration of HBO early after neonatal GMH also normalized brain atrophy,
      splenomegaly, and cardiac hypertrophy 1 month after injury. CONCLUSION: This
      study supports the role of hyperbaric oxygen (HBO) treatment in the early period
      after neonatal GMH. HBO is an effective strategy to help protect the infant's
      brain from the post-hemorrhagic consequences of brain atrophy, mental
      retardation, and cerebral palsy. Further studies are necessary to determine the
      mechanistic basis of these neuroprotective effects.

PMID- 21725765
TI  - Thrombin preconditioning attenuates iron-induced neuronal death.
AB  - Pretreatment with a low dose of thrombin attenuated brain injury after
      intracerebral hemorrhage (ICH) or cerebral ischemia. This phenomenon has been
      called thrombin preconditioning (TPC). The current study investigated whether or
      not TPC reduces neuronal death induced by iron in cultured neurons. The roles of
      protease-activated receptors (PARs) and the p44/42 mitogen-activated protein
      kinase (p44/42MAPK)/70-kDa ribosomal protein S6 kinase (p70S6K) signal
      transduction pathway in TPC were also examined. This study had three parts: (1)
      primary cultured neurons were pretreated with vehicle, thrombin or PAR agonists.
      Cell death was induced by ferrous iron (500 MUM) 24 h later. After 48 h, culture
      medium was collected for lactate dehydrogenase measurement; (2) neurons were
      treated with vehicle, thrombin or thrombin plus PPACK (D-Phe-Pro-Arg
      chloromethylketone) thrombin and were collected for Western blotting; (3) the
      effect PD098059 on TPC was examined. Cells were treated with 20 MUM PD098059 or
      vehicle 1 h before TPC. Neuron viability was measured 24 h following exposure to
      ferrous iron. Preconditioning with thrombin or PAR agonists reduced iron-induced
      neuronal death (p<0.05). Thrombin, but not PPACK thrombin, upregulated the
      protein levels of activated p44/42 MAPK and p70 S6K (p<0.05) in neurons. PD098059
      also abolished the TPC-induced neuronal protection against iron (p<0.05). In
      conclusion, the protective effect of thrombin preconditioning is partially
      achieved through activating PARs and the p44/42 MAPK/p70S6K signal transduction
      pathway.

PMID- 21725766
TI  - Granulocyte colony-stimulating factor treatment provides neuroprotection in
      surgically induced brain injured mice.
AB  - Surgically induced brain injury (SBI) is a common concern after a neurosurgical
      procedure. Current treatments aimed at reducing the postoperative sequela are
      limited. Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth
      factor involved in the inflammatory process, has been shown in various animal
      models to be neuroprotective. Consequently, in this study, we investigated the
      use of G-CSF as a treatment modality to reduce cell death and brain edema, while
      improving neurobehavioral deficits following an SBI in mice. Eleven-week-old C57
      black mice (n=76) were randomly placed into four groups: sham (n=19), SBI (n=21),
      SBI with G-CSF pre-treatment (n=15) and SBI with G-CSF pre/post-treatment (n=21).
      Treated groups received a single dose of G-CSF intraperitoneally at 24, 12 and 1
      h pre-surgery and/or 6 and 12 h post-surgery. Postoperative assessment occurred
      at 24 h and included neurobehavioral testing and measurement for both cell death
      and brain edema. Results indicated that pre-treatment with G-CSF reduced both
      cell death and brain edema, while post-treatment reduced neurobehavioral
      deficits. This study implies that the morphological changes in the brain are
      effected by pre-treatment; however, in order to activate and/or amplify targets
      involved in the recovery process, more dosing regimens may be needed.

PMID- 21725767
TI  - Tamoxifen treatment for intracerebral hemorrhage.
AB  - Tamoxifen is a selective estrogen receptor modulator. In this study we
      investigated whether or not tamoxifen reduces intracerebral hemorrhage (ICH)
      induced brain injury in rats. In all experiments, adult male Sprague-Dawley rats
      received an injection of 100 MUL autologous whole blood into the right basal
      ganglia. In the first set of experiments, rats were treated with tamoxifen (2.5
      mg/kg or 5 mg/kg, i.p.) or vehicle 2 and 24 h after ICH and were killed at day 3
      for brain edema measurement. In the second set of experiments, rats were treated
      with tamoxifen (5 mg/kg) or vehicle and magnetic resonance imaging (MRI), and
      behavior tests were performed at days 1, 7, 14 and 28. Rats were killed at day 28
      for brain histology. We found that tamoxifen at 5 but not at 2.5 mg/kg reduced
      perihematomal brain edema at day 3 (p<0.05). Brain histology showed that
      tamoxifen reduced caudate atrophy at day 28 (p<0.01). Tamoxifen also improved
      functional outcome (p<0.05). MRI demonstrated a tendency to smaller T2* lesions
      in tamoxifen-treated rats. However, two out of five rats treated with tamoxifen
      developed hydrocephalus. These results suggest that tamoxifen has neuroprotective
      effects in ICH, but the cause of hydrocephalus development following tamoxifen
      treatment needs to be examined further.

PMID- 21725768
TI  - Prostaglandin E2 EP1 receptor inhibition fails to provide neuroprotection in
      surgically induced brain-injured mice.
AB  - Recent trials have shown that the prostaglandin E2 EP1 receptor is responsible
      for NMDA excitotoxicity in the brain after injury. Consequently, in this study,
      we investigated the use of SC-51089, a selective prostaglandin E2 EP1 receptor
      antagonist, as a pre-treatment modality to decrease cell death, reduce brain
      edema, and improve neurobehavioral function after surgically induced brain injury
      (SBI) in mice. Eleven-week-old C57 black mice (n=82) were randomly assigned to
      four groups: sham (n=31), SBI (n=27), SBI treated with SC51089 at 10 MUg/kg
      (n=7), and SBI treated with SC51089 at 100 MUg/kg (n=17). Treated groups received
      a single dose of SC51089 intrapertioneally at 12 and 1 h pre-surgery. SBI was
      performed by resecting the right frontal lobe using a frontal craniotomy.
      Postoperative assessment occurred at 24 and 72 h, and included neurobehavioral
      testing and measurement of brain water content and cell death. Results indicated
      that neither low- nor high-dose EP1 receptor inhibition protected against the SBI
      related effects on brain edema formation or cell death. There was however a
      significant improvement in neurobehavioral function 24 h post-SBI with both
      dosing regimens. Further studies will be needed to assess the potential
      therapeutic role of EP1 receptor targeting in SBI.

PMID- 21725769
TI  - Mucosal tolerance to brain antigens preserves endogenous TGFbeta-1 and improves
      neurological outcomes following experimental craniotomy.
AB  - Intracranial surgery causes brain damage from cortical incisions, intraoperative
      hemorrhage, retraction, and electrocautery; collectively these injuries have
      recently been coined surgical brain injury (SBI). Inflammation following SBI
      contributes to neuronal damage. This study develops T-cells that are
      immunologically tolerant to brain antigen via the exposure of myelin basic
      protein (MBP) to airway mucosa. We hypothesize that these T-cells will migrate to
      the site of corticotomy, secrete immunosuppressive cytokines, such as TGFbeta1,
      reduce inflammation, and improve neurological outcomes following SBI. A standard
      model for SBI was used for this experiment. C57 mice were divided into six
      groups: SHAM+Vehicle, SHAM+Ovalbumin, SHAM+MBP, SBI+Vehicle, SBI+OVA, and
      SBI+MBP. Induction of mucosal tolerance to vehicle, ovalbumin, or MBP was
      performed prior to SBI. Neurological scores and TBFbeta1 cytokine levels were
      measured 48 h postoperatively. Mice receiving craniotomy demonstrated a reduction
      in neurological score. Animals tolerized to MBP (SBI+MBP) had better
      postoperative neurological scores than SBI+Vehicle and SBI+OVA. SBI inhibited the
      cerebral expression TGFbeta1 in PBS and OVA treated groups, whereas MBP treated
      animals preserved preoperative levels. Mucosal tolerance to MBP leads to
      significant improvement in neurological outcome that is associated with the
      preservation of endogenous levels of brain TGFbeta1.

PMID- 21725770
TI  - Effects of progesterone and testosterone on ICH-induced brain injury in rats.
AB  - Studies have shown that progesterone reduces brain injury, whereas testosterone
      increases lesion size after ischemic stroke. This study examined the effects of
      progesterone and testosterone on intracerebral hemorrhage (ICH)-induced brain
      injury. Male Sprague-Dawley rats received an injection of 100 MUL autologous
      whole blood into the right basal ganglia. Progesterone (16 mg/kg), testosterone
      (15 mg/kg) or vehicle was given intraperitoneally 2 h after ICH. Behavioral tests
      were performed, and the rats were killed after 24 h for brain edema measurement.
      Perihematomal brain edema was reduced in progesterone-treated rats compared to
      vehicle-treated rats (p<0.05). Progesterone also improved functional outcome
      following ICH (p<0.05). Testosterone treatment did not affect perihematomal edema
      formation, but resulted in lower forelimb placing score (p<0.05). In conclusion,
      progesterone can reduce brain edema and improve functional outcome, whereas
      testosterone may have a deleterious effect after ICH in male rats.

PMID- 21725771
TI  - Drug repurposing for vascular protection after acute ischemic stroke.
AB  - The attempts to develop new treatments for acute ischemic stroke have been
      fraught with costly and spectacularly disappointing failures. Repurposing of
      safe, older drugs provides a lower risk alternative. Vascular protection is a
      novel strategy for improving stroke outcome. Promising targets for vascular
      protection after stroke have been identified, and several of these targets can be
      approached with "repurposed" old drugs, including statins, angiotensin receptor
      blockers (ARBs), and minocycline. We tested the vascular protection (ability to
      reduce hemorrhagic transformation) of three marketed drugs (candesartan,
      minocycline, and atorvastatin) in the experimental stroke model using three
      different rat strains [Wistar, spontaneously hypertensive rats (SHR) and type 2
      diabetic Goto-Kakizaki (GK) rats]. All agents decreased the infarct size,
      improved the neurological outcome and decreased bleeding. Mechanisms identified
      include inhibition of MMP-9, activation of Akt, and increased expression of
      proangiogenic growth factors. Premorbid vascular damage (presence of either
      diabetes or hypertension) increased the likelihood of vascular injury after
      ischemia and reperfusion and improved the response to vascular protection.

PMID- 21725772
TI  - Erythropoietin attenuates inflammatory factors and cell death in neonatal rats
      with intracerebral hemorrhage.
AB  - Stroke affects infants at a rate of 26/100,000 live births each year. Of these
      strokes, approximately 6.7 are hemorrhagic strokes. Erythropoietin (EPO) is an
      anti-apoptotic and neuroprotective hormone. In adult rodents, EPO attenuates
      inflammatory factor expression and blood-brain barrier damage after intracerebral
      hemorrhage (ICH). However, the effect of EPO in neonatal ICH stroke remains
      unexplored. This investigation aimed to elucidate the underpinnings of
      inflammation after ICH in postnatal day 7 (P7) rats and the effect of human
      recombinant EPO (hrEPO) treatment on ICH-induced inflammation. The P7 rat pups
      were pretreated with hrEPO (5,000 U/kg i.p.) or saline vehicle 4 h prior to the
      induction of ICH by blood injection into the right cerebral cortex and basal
      ganglia. Supplemental half doses of hrEPO treatment or saline injections were
      subsequently given 16 h after ICH induction. Real-time PCR done 24 h after ICH
      showed reductions in interleukin1-beta (IL1-beta), interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNFalpha) mRNA expression in the basal ganglia of the
      hrEPO-treated rats compared to saline-treated rats. Terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) staining indicated fewer dying cells
      in the hrEPO-treated brain. Our data suggest that hrEPO has an anti-inflammatory
      action in neonates after ICH. The suppression of inflammatory cascades likely
      contributes to hrEPO's neuroprotective effect, which may be explored as a
      therapeutic treatment for ICH.

PMID- 21725773
TI  - Protective effects of hydrogen on fetal brain injury during maternal hypoxia.
AB  - This study aimed to investigate the effects of hydrogen on fetal brain injury
      during maternal hypoxia. Pregnant rats (n=12, at gestational day 17) were
      randomly assigned into three groups; air, hypoxia, and hypoxia plus hydrogen
      groups were put into a chamber and flushed with room air (21% O2 and 79% N2),
      hypoxia (8% O2 and 92% N2), and hypoxia with hydrogen mixture (2% H2, 8% O2 and
      90% N2), respectively, for 4 consecutive hours. After birth, body and brain
      weights, body-righting reflex, and negative geotropism of neonates were measured,
      and then pups were killed at days 1 and 7. Oligodendrocytes were studied at post
      natal day 1 by immunohistochemistry. We found significant decreases in body
      weight in the hypoxia group (P<0.05 vs. room air group), but not in the hypoxia
      plus hydrogen group (P>0.05 vs. room air group). Even though brain weight was not
      different among groups, the brain weight to body weight ratio in the room air
      group was significantly (P<0.05) lower than that in the hypoxia alone or hypoxia
      plus hydrogen groups. Body-righting reflex at day 1 and negative geotropism at
      days 3-4 showed deficiency in hypoxia animals when compared with the room air
      group (P<0.05). Hydrogen treatment improved the body-righting reflex and negative
      geotropism (P<0.05 vs. room air group). The above-mentioned functional changes
      caused by hypoxia were not associated with morphology and cell death of
      oligodendrocytes. Therefore, the maternal hypoxia-induced body weight loss, and
      functional abnormalities and hydrogen treatment during hypoxia offered a
      protective effect and improved functions in neonates.

PMID- 21725775
TI  - Intracerebral hemorrhage and meteorological factors in Chongqing, in the
      southwest of China.
AB  - Studies have reported the relationship between intracerebral hemorrhage (ICH) and
      meteorological factors. However, few of those study analyses were dependent on
      daily meteorological factors. The aim of this study is to evaluate the
      relationship between various meteorological data and ICH cases from Chongqing, in
      the southwest of China. One thousand nineteen intracerebral hemorrhage events
      registered in our hospital were recorded from 1 January 2006 to 30 August 2009.
      Meteorological parameters were analyzed, including season, month, air
      temperature, humidity, atmospheric pressure, visibility, presence of fog, and
      wind velocity. The chi-square test for goodness of fit was used for statistical
      evaluations. Significant differences in seasonal and monthly patterns of ICH
      onset were observed. The incidence of ICH attack was highest in winter and lowest
      in summer (p<0.0001). The monthly variation was consistent with the above pattern
      (p=0.002). Daily air temperature (p<0.0001), humidity (p=0.002), and atmospheric
      pressure (p<0.0001) were associated with the admission rate. However, no
      significant relationships were found between visibility (p=0.62), presence of fog
      (p=0.32), or wind velocity (P=0.5) and the risk of ICH. Our study demonstrates
      that the incidence of ICH is closely related to some meteorological factors, such
      as season, daily air temperature, humidity, and atmospheric pressure.

PMID- 21725774
TI  - Neuroglobin expression in human arteriovenous malformation and intracerebral
      hemorrhage.
AB  - We reported previously that Notch signaling is activated in human arteriovenous
      malformations (AVMs) and that intracerebral hemorrhage (ICH) in humans is
      accompanied by increased neurogenesis. The former phenomenon may be involved in
      AVM pathogenesis and the latter in the brain's response to ICH-induced injury.
      Here we describe increased expression of the hypoxia-inducible neuroprotective
      protein, neuroglobin (Ngb), in neurons surrounding unruptured AVMs and in the
      perihematomal region adjacent to ICH. In these disorders, as in other clinical
      settings, such as ischemic stroke, AVM- and ICH-induced overexpression of Ngb may
      be stimulated by ischemic hypoxia and may help to constrain brain injury.

PMID- 21725776
TI  - Timing pattern of onset in hypertensive intracerebral hemorrhage patients.
AB  - The temporal pattern of onset of hypertensive intracerebral hemorrhage (ICH) has
      been evaluated in previous reports, but there are few published data on this
      pattern in Chongqing, China. The purpose of this study is to explore the temporal
      pattern of diurnal, weekly and monthly variations in the onset of hypertensive
      ICH from a hospital-based population. The study retrospectively reviewed 230
      residents who suffered from hypertensive ICH between January 2008 and August 2009
      in our hospital. The temporal pattern was investigated by hours, days and months.
      Chi-square test for goodness of fit was used for statistical analysis.
      Significant differences of the onset time of hypertensive ICH patients could be
      seen in diurnal variation (p=0.000) and in monthly variation (p=0.000), but could
      not be found in weekly variation (p=0.466). There was a bimodal distribution in
      diurnal variation, and monthly variation showed that the occurrence of
      hypertensive ICH mainly focuses on the period from December to May. Our study
      demonstrated the existence of diurnal and monthly variations and no significant
      weekly variation can be found in the time of onset of hypertensive ICH.

PMID- 21725777
TI  - "Weekend effects" in patients with intracerebral hemorrhage.
AB  - Studies have shown that weekend admissions are associated with outcomes of
      patients with different diseases. Our aim is to evaluate the weekend effects in
      patients with intracerebral hemorrhage (ICH) in our hospital. A retrospective
      analysis of patients with ICH was performed. Weekend admission was defined as the
      period from Friday, 6:01 p.m., to Monday, 7:59 a.m. The ICH score was used to
      evaluate severity on admission. The chi-square goodness-of-fit test was applied
      to analyze weekly distribution. The rank sum test was conducted to calculate the
      functional outcomes (modified Rankin scale, MRS), and the mortality was compared
      by binary logistic regression. Between 2008 and 2009, 313 patients with ICH were
      included, of which 30% (95/313) were admitted on the weekend. Patients with ICH
      were equally distributed on weekdays and weekends (P=0.7123). Weekend admission
      was not a statistically significant predictive factor for in-hospital mortality
      (P=0.315) and functional outcomes (P=0.128) in patients with ICH. However, a
      significant correlation was found between the ICH score and the mortality
      (OR=6.819, 95%CI: 4.323-10.757; P=0.009). Our results suggest that compared with
      weekday admission, weekend admission is not significantly associated with
      increased short-term mortality and poorer functional outcome among patients
      hospitalized with ICH.

PMID- 21725778
TI  - Disparities in medical expenditure and outcomes among patients with intracranial
      hemorrhage associated with different insurance statuses in southwestern China.
AB  - As the economic impact of intracranial hemorrhage (ICH) has not been well
      characterized before, the purpose of this study is to investigate the prognosis
      of ICH patients with different insurances in southwestern China. This study used
      hospital data from December 2005 to September 2009. All patients with a final
      discharge diagnosis of acute ICH were enrolled. Patients were divided by payer
      sources. Hospital expenditure, length of hospital stay (LOS) and outcome during
      hospitalization were analyzed. SAS 9.1 software was utilized for the Kruskal
      Wallis test and multivariate logistic regression analysis. There were 1,091 adult
      subjects who met the inclusion criteria of ICH. Hospital costs were remarkably
      higher for local medical insurance beneficiaries than for the nonlocally insured
      group and the uninsured group. The locally insured group had the longest LOS
      compared to the uninsured and nonlocally insured groups. There were significant
      outcome differences between the locally insured and uninsured groups. However, we
      noted that locally insured patients seemed to have higher in-hospital mortality
      from ICH. In spite of acquiring insurance, these ICH subjects did not appear to
      have better outcomes. The results emphasize the need for improvement in health
      care policy.

PMID- 21725779
TI  - Clinical analysis of electrolyte imbalance in thalamic hemorrhage patients within
      24 h after admission.
AB  - We have observed that patients with thalamic hemorrhage are more likely to have
      electrolyte disturbances than those with non-thalamic hemorrhage. Here, we are
      attempting to provide some comprehensive information on electrolyte disturbances
      in patients with thalamic hemorrhage. Retrospectively, 67 patients with thalamic
      hemorrhage (TH group) and 256 with non-thalamic hemorrhage (N-TH group) were
      found from computer tomography images. Electrolytes of these patients were tested
      within 24 h after hospitalization. Chi-square test was used to compare the
      incidence of electrolyte imbalance. Serum K+ levels were found to be abnormal in
      37.31% of the patients in the TH group and 24.21% in the N-TH group, and the
      difference was significant (p<0.05). Such a difference was also observed for the
      levels of serum Na+ and Cl+. Incidences of abnormal serum K+ (p<0.05), Na+
      (p<0.01) and Cl(-) (p<0.01) levels were different among thalamic hemorrhage,
      basal ganglia area hemorrhage and lobar hemorrhage patients. In the TH group, the
      mortality of patients with electrolyte disturbances (42.50%) was higher than that
      of patients with normal electrolyte levels (14.81%, p<0.05). The incidence of
      electrolyte imbalance is higher in patients with thalamic hemorrhage than in
      those with non-thalamic hemorrhage. The reason may be partly related to the
      location of the hemorrhage. Electrolyte disturbance may contribute to the higher
      mortality of patients with thalamic hemorrhage.

PMID- 21725780
TI  - Characteristics of pulse pressure parameters in acute intracerebral hemorrhage
      patients.
AB  - We explored the features of changes in pulse pressure (PP) in patients with
      intracerebral hemorrhage (ICH). Two hundred one patients with ICH were admitted
      to our hospital from January 2008 to August 2009. Meanwhile, another 201 people
      matching in age and gender with these patients were assigned as controls. Blood
      Pressures (BP) were collected within the first 24 h after admission. PP was
      calculated from the BP readings. The mean of PPs was compared via T-test. The
      distributed frequency of the PP level was analyzed using the chi-square test. PPs
      in the ICH group were higher than those of the controls (P<0.001). Chi-square
      test showed a significant difference in distribution ratios of PP (P<0.01)
      between the ICH and control group. The largest PP range in the ICH group was from
      80 to 99 mmHg, which accounted for 33.3%; PP of the control group was from 40 to
      49 mmHg (30.3%). The PP level in the 40-89-year-old case group was higher than
      that in the 40-89-year-old control group. PP increased with age. Our
      investigation indicates that higher PP is correlated with acute ICH and that PP
      is important in predicting the risk of ICH.

PMID- 21725781
TI  - Electrocardiographic abnormalities in patients with intracerebral hemorrhage.
AB  - BACKGROUND: Stroke is frequently followed by electrocardiographic changes.
      Although electrocardiographic abnormalities are well known in ischemic stroke and
      subarachnoid hemorrhage, these changes have only rarely been investigated
      systematically in patients with intracerebral hemorrhage. The purpose of this
      study is to investigate the prevalence and characterization of ECG abnormalities
      in a consecutive series of ICH patients who had no history of heart disease.
      METHODS: The study was retrospective, and 304 intracerebral hemorrhage patients
      who met the study criteria were entered in the study. The ECG changes of the 304
      acute hemorrhagic stroke patients without primary heart disease were analyzed.
      The relationship among the electrocardiographic abnormalities, the location of
      hematoma, and the clinical outcome were investigated to determine cardiac
      involvement in the cerebral hemorrhage in these patients. RESULTS: A total of 304
      patients were included. Two hundred and four patients (67.1%) had one or more ECG
      abnormalities. These changes included morphological waveform changes and
      arrhythmias, such as QTc prolongation, ST-T morphological changes, sinus
      bradycardia, inverted T wave, and conduction block. These ECG changes were not
      related to the level of the cerebral lesion, but were related to its location and
      the outcome. CONCLUSIONS: Electrocardiographic abnormalities frequently occur
      after intracerebral hemorrhage, and these changes were not related to the level
      of the cerebral lesion, but were related to the location of the cerebral lesion
      and the outcome.

PMID- 21725782
TI  - ECG change of acute subarachnoid hemorrhagic patients.
AB  - OBJECTIVE: This study intends to investigate whether the entry
      electrocardiographic (ECG) abnormalities of patients with acute subarachnoid
      hemorrhage (SAH) are related to the prognosis. METHODS: From 1998 to the present,
      106 SAH patients who had no history of heart disease and were diagnosed with head
      CT were recruited. RESULTS: Abnormal ECG changes of acute subarachnoid hemorrhage
      patients were observed, with a total incidence rate of 63.2% (67/106). The
      incidence rate of allorhythmia was 22.6% (24/106), the repolarization abnormality
      was 14.2% (15/106), the conduction abnormality was 1.9% (2/106), and the combined
      abnormality was 21.7% (23/106). However, dividing the patients into two groups
      according to their entry consciousness state, no difference was observed between
      coma and alert groups (P=1.0000). In addition, the ECG changes had no
      relationship with the lesion degree and the outcome prognosis according to
      logistic regression analysis (P=0.0844). CONCLUSIONS: In 106 SAH patients, we
      could not identify any relationship between the ECG and lesion degree and outcome
      prognosis.

PMID- 21725783
TI  - Diagnosis and treatment of hemorrhagic pituitary adenomas.
AB  - We retrospectively analyzed the clinical manifestations, imaging results, and
      surgical treatment conditions of 72 patients who were diagnosed with hemorrhagic
      pituitary adenoma between January 2006 and May 2009 at our Department of
      Neurosurgery. We reached the conclusion that the CT-positive rate was 55.17% and
      the MRI-positive rate was 94.44%. Sixty-six patients underwent transsphenoidal
      operations; 6 patients, transfrontal operations; 52, total resections; 10,
      subtotal resections; and 10, partial resections. All procedures alleviated
      patients' headaches and stopped vomiting; patients with impaired consciousness
      gradually became clear-headed after the operations; patients whose preoperative
      eyesight had been impaired improved to different degrees, and ophthalmoplegia
      improved. Fifty-six patients were followed, 14 were cured, 32 had alleviated
      symptoms but 4 did not, and 6 relapsed. Our finding suggests that MRI scanning is
      superior to CT scanning in the diagnosis of hemorrhagic pituitary adenomas.
      Surgical decompression should be performed as soon as possible, and
      transsphenoidal microsurgery is the optimal treatment.

PMID- 21725784
TI  - Characteristics of acute cerebral hemorrhage with regard to lipid metabolism and
      glycometabolism among different age groups.
AB  - OBJECTIVE: This study investigated the lipid metabolism and glycometabolism of
      patients with acute cerebral hemorrhage from 2006-2008 in order to find a
      possible association among lipid metabolism, glycometabolism and different age
      groups of adults in the Chinese Chongqing population. METHODS: Data on levels of
      total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low
      density lipoprotein (LDL-C) and fasting serum glucose (GLU) were obtained from
      records of patients (548) from the Department of Neurology of the First
      Affiliated Hospital of Chongqing Medical University. Participants ranging in age
      from 21-94 years were divided into three groups; the first group was the young
      group in which all participants were 21-44 years old; the second group was the
      middle-age group in which all participants were 45-59 years old, and the last
      group was the elderly group in which all participants were 60-94 years old.
      RESULTS: Levels of TC, TG, HDL-C, LDL-C and GLU were not significantly different
      among the three groups (P>0.05). Proportions of hypercholesterolemia high LDL-C,
      low HDL-C, impaired fasting glucose and diabetes mellitus were not different
      among the three groups (P>0.05). Only the proportion of hypertriglyceridemia
      patients was significantly different. The risk of being diagnosed with
      hypertriglyceridemia in the middle-age group was increased 2.371 times (95% CI:
      1.542-3.645) and in the young group increased 2.281 times (95% CI: 1.211 -4.296).
      CONCLUSION: Age and hypertriglyceridemia are risk factors associated with an
      increased incidence rate of acute cerebral hemorrhage in the Chongqing population
      in China.

PMID- 21725785
TI  - The role of a high augmentation index in spontaneous intracerebral hemorrhage to
      prognosticate mortality.
AB  - The aim of the study was to determine the prognostic value of a high augmentation
      index, which was a surrogate marker of arterial stiffness in patients with
      spontaneous intracerebral hemorrhage. The outcome was divided into two groups in
      which the following data were collected in a computer running SphygmoCor CvMS
      software version 8.2. Logistic regression analysis was carried out among
      significant variables to identify an independent predictor of 6-month outcome and
      mortality. Sixty patients were recruited into the study. Admission Glasgow Coma
      Scale score (OR, 0.7; 95% CI, 0.450-0.971; P=0.035), total white cell count (OR,
      1.2; 95% CI, 1.028-1.453; P=0.023) and hematoma volume (OR, 1.1; 95% CI, 1.024
      1.204; P=0.011) were found to be statistically significant for identifying poor 6
      month outcome in multivariate analysis. Factors independently associated with
      mortality were a high augmentation index (OR, 8.6; 95% CI, 1.794-40.940; P=0.007)
      and midline shift (OR, 7.5; 95% CI, 1.809-31.004; P=0.005). Admission Glasgow
      Coma Scale score, total white cell count and hematoma volume were significant
      predictors for poor 6-month outcome, and a high augmentation index and midline
      shift were predictors for 6-month mortality in this study.

PMID- 21725786
TI  - Effect of minimally invasive aspiration in treatment of massive intracerebral
      hemorrhage.
AB  - OBJECTIVE: To observe the effect of minimally invasive aspiration combined with
      medication in patients with massive spontaneous intracerebral hemorrhage.
      METHODS: Twenty-three patients with massive primary intracerebral hematoma (>50
      mL), presenting with depressed consciousness, were recruited. Minimally invasive
      aspiration was applied within 72 h after onset, along with mannitol or furosemide
      to lower the intracranial pressure and symptomatic treatment. RESULTS: Within 1
      month after hemorrhage, three patients recovered to normal activity; the
      consciousness level of eight had improved; three patients remained stable; three
      patients had aggravated conditions and were discharged automatically (two with
      rehemorrhage and one with complications). Six patients died (hematoma volume of
      all patients was above 80 mL). CONCLUSIONS: Minimally invasive aspiration may be
      effective in patients with massive intracerebral hemorrhage, but it had a poor
      prognosis for those patients whose hematoma volume was above 80 mL.

PMID- 21725787
TI  - Retrospective analysis of the predictive effect of coagulogram on the prognosis
      of intracerebral hemorrhage.
AB  - OBJECTIVE: To determine the effective index of coagulogram after acute
      intracerebral hemorrhage (ICH) for predicting the outcome of ICH. METHODS: A
      total of 641 patients with ICH were divided into two groups: the effective
      treatment group (healing well and improving) and ineffective treatment group (non
      improving and dying). The coagulogram results of the two groups were analyzed
      with SPSS software 13.0, including PT, APTT, TT, and Fbg. The differences in
      these parameters were found by independent samples T test and Kruskal-Wallis test
      between the two groups. Then, the different parameters were obtained by logistic
      regression, which were significantly associated with the prognosis of acute
      cerebral hemorrhage patients. In addition, the odds ratio for the special
      indicators was calculated by chi-square test. RESULTS: Only PT had a significant
      difference between the groups (p<0.05) among the four parameters. The binary
      logistic regression analysis indicated that PT (p=0.003) and APTT (p=0.043) were
      related to the outcome of ICH patients. According to the chi-square test, the OR
      (odds ratio) of prolonged PT is 2.40 (1.34-4.29 with 95% CI) and that of
      prolonged APTT is 1.57 (1.01-2.42 with 95% CI). CONCLUSION: Prolonged PT and APTT
      are risk factors affecting the prognosis of ICH patients. Monitoring and
      controlling PT and APTT are advisable for improving the prognosis of ICH
      patients.

PMID- 21725788
TI  - Risk factors of early death in patients with hypertensive intracerebral
      hemorrhage during hospitalization.
AB  - Hypertensive intracerebral hemorrhage (ICH) is the deadliest, most disabling and
      least treatable form of acute cerebral accident. A large number of patients die
      in a short time after the hemorrhage. However, the risk factors of early death in
      this pattern are still in debate. A case control study of 273 patients with
      hypertensive ICH admitted to our hospital was carried out. The patients were
      divided into the death group and survival group according to clinical outcome
      during hospitalization. Any possible risk factors were assessed using univariate
      and multivariate analysis. The logistic regression analysis revealed that the
      following four factors were independently associated with early death: age [odds
      ratio (OR), 0.966; 95% confidence interval (CI), 0.936-0.997; P=0.0327], GCS
      score (OR, 1.192; 95% CI, 1.090-1.303; P<0.001) and systolic pressure (OR, 0.939;
      95% CI, 0.772-1.142; P<0.001) at admission, and hematoma volume (OR, 0.8000; 95%
      CI, 0.807-0.959; P=0.0037). Cranial computed tomography imaging is an important
      examination method to evaluate the clinical outcome. Effective prevention of
      hypertension and adequate reduction of blood pressure at admission are
      recommended as the major measures to improve the prognosis of hypertensive ICH.

PMID- 21725789
TI  - Effects of early serum glucose levels on prognosis of patients with acute
      intracerebral hemorrhage.
AB  - Studies have indicated that hyperglycemia might cause cerebral damage to patients
      after acute intracerebral hemorrhage (ICH). But systematic studies on the effects
      of diabetes, stress hyperglycemia and normal serum glucose level on the prognosis
      of ICH patients are insufficient. It is essential to explore the prognosis among
      them. According to their serum glucose level within 24 h, 189 patients with ICH
      were divided into three groups: diabetes (group A), stress hyperglycemia (group
      B) and normal serum glucose (group C). The activity of daily living ability of
      patients was evaluated by Barthel index at 30 days after admission. The data
      analysis was done using cumulative logit model and rank sum test. Significant
      differences were observed in prognosis between group A and group C (OR: 0.056;
      CI: 0.022-0.143; p<0.0001), B and C (OR: 0.081; CI: 0.039-0.167; p<0.0001),
      respectively; there was no significant difference between A and B (p>0.05). No
      difference was found between A and B in the early serum glucose level, but
      significant differences were observed between A and C, and between B and C. Early
      hyperglycemia may worsen the prognosis of ICH patients, though patients with
      diabetes or stress hyperglycemia after ICH may have similar outcomes when early
      serum glucose levels fluctuate within the same range.

PMID- 21725790
TI  - Prognosis study of 324 cases with spontaneous intracerebral hemorrhage in
      Chongqing, China.
AB  - We aimed to investigate the clinical characteristics of intracerebral hemorrhage
      (ICH) in Chongqing City, China, and evaluate some factors predicting the
      prognosis of ICH. We collected 324 cases with spontaneous intracerebral
      hemorrhage in our hospital from January 2008 to November 2009. Univariate
      variance analyses were used for comparison of characteristics. Odds ratios (ORs)
      were calculated by logistic regression. Potential confounders were adjusted,
      including gender, age, smoking, and drinking status. Hypertension was the major
      cause of the spontaneous intracerebral hemorrhage, accounting for 75% of all
      patients in this study. Hemorrhages were located in lobes (22.5%), basal ganglia
      (65.3%), cerebral ventricles (2.6%), cerebellum (4.2%), and brain stem (7.4%).
      Serum glucose and conscious status were independently associated with in-hospital
      mortality after ICH. Comparing subjects who died in the hospital to those who
      survived, the adjusted ORs of serum glucose were 1.248 (95% CI 1.013-1.537,
      p=0.037), and the adjusted ORs of consciousness status were 1.995 (95% CI 1.519
      2.621, p<0.001). In China, spontaneous intracerebral hemorrhage is mostly caused
      by hypertension and is usually located in the basal ganglia. Serum glucose and
      consciousness status independently predict the prognosis of ICH.

PMID- 21725791
TI  - Retrospective analysis of the predictive effect of routine biochemical results on
      the prognosis of intracerebral hemorrhage.
AB  - OBJECTIVE: To find the effective biochemical factors for predicting the outcome
      of acute intracerebral hemorrhage (ICH). METHODS: According to the outcome, 497
      ICH patients were divided into two groups (effective treatment group, ineffective
      treatment group). The routine biochemical results were analyzed between groups
      with SPSS software 13.0, including TC, TG, HDL-c, LDL-c, UA, and Glu. The
      differences of these items were found by independent sample T test and Kruskal
      Wallis test between groups. Then the items, which were significantly associated
      with the prognosis of ICH patients, were obtained by the logistic regression. In
      addition, we calculated the odds ratio (OR) for the special indicators by chi
      square test. RESULTS: Only UA, Glu, and HDL-c had significant differences between
      groups (P<0.05) among the six biochemical items. The binary logistic regression
      analysis indicated that high Glu and UA were related to the outcome of ICH
      (P<0.01). By chi-square test, the OR of high Glu was 3.95 (2.27-6.87 with 95% CI)
      and that of high UA was 2.19 (1.16-4.11 with 95% CI), but HDL-c's OR was only
      0.90 (0.41-1.98 with 95% CI) without statistical significance. CONCLUSION: High
      Glu and UA were risk factors for the prognosis of ICH; monitoring and controlling
      the Glu and UA may be advisable improving the prognosis of ICH.

PMID- 21725792
TI  - Alteplase (rtPA) treatment of intraventricular hematoma (IVH): safety of an
      efficient methodological approach for rapid clot removal.
AB  - Intraventricular hemorrhage (IVH) subsequent to intracerebral hemorrhage (ICH) or
      subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity.
      The use of fibrinolytic agents to treat this condition has previously been
      reported in small clinical trials with limited numbers of patients. Variability
      regarding inclusion criteria, method of administration and outcome have made it
      difficult to draw firm conclusions regarding the efficacy of antifibrinolytic
      therapy. Nine patients with CT-diagnosed IVH were treated with Alteplase
      intrathecally for 3 to 5 days according to the CT-verified clearance of IVH.
      After the treatment period, a repeat CT scan was performed to evaluate treatment
      effect.In this safety study, we achieved rapid removal of IVH compared to
      retrospective controls, without incidents of re-bleeding, with only 33% permanent
      shunt placements and a neurological outcome of GOS of 4-5 in 44% of the patients.
      Based on the above results, the treatment protocol was considered safe and highly
      effective. A prospective randomized national multicenter trial has been initiated
      in order to evaluate the efficacy of this novel method also in terms of outcome
      and shunt dependency.

PMID- 21725793
TI  - Decompressive hemi-craniectomy is not necessary to rescue supratentorial
      hypertensive intracerebral hemorrhage patients: consecutive single-center
      experience.
AB  - OBJECTIVE: A consensus on decompressive surgery for hypertensive intracranial
      hemorrhage (ICH) has not been reached. We retrospectively analyzed our single
      center experience with ICH. MATERIAL AND METHODS: From January 2004 to August
      2009, 65 consecutive supratentorial ICH patients underwent surgery in our
      institute. Supratentorial ICHs that exhibited a hematoma volume of over 50 mL
      according to the xyz/2 method were included in this study. We compared a hematoma
      removal plus decompressive craniectomy group (DC) and a hematoma removal group
      (HR) with regard to GCS, preoperative hematoma volume, shift from the midline,
      time from the ictus to surgery, post-surgical hematoma volume, brain swelling,
      hospitalization periods, and m-RS after 3 months. Statistical analysis was done
      using the t-test or chi2 test, and the odds ratio was calculated. RESULTS: Twenty
      five patients participated in this study. The DC group included 5 male patients,
      and the HR group 20 patients (F/M=8/12). Mean DC group age was 44.2 years, and
      56.8 years for the HR group (p<0.05). GCS, preoperative hematoma volume, shift
      from the midline, time from the ictus to surgery, and postoperative hematoma
      volume were similar between both groups. Brain swelling on post-operative
      [corrected] CT was demonstrated to be mild and delimited within the cranium in
      the DC group, similar to the HR group. Hospitalization periods increased in the
      DC group (p<0.05). The m-RS after 3 months was similar for both groups. The
      factors relevant for m-RS were age, postoperative hematoma volume, and GCS at 24
      h after surgery. CONCLUSION: Decompressive craniectomy is not necessary for
      rescue in ICH if the hematoma can be removed completely.

PMID- 21725794
TI  - Intravascular hypothermia for acute hemorrhagic stroke: a pilot study.
AB  - The use of intravascular hypothermia in the treatment of hemorrhagic stroke is
      currently still being researched. The exact therapeutic properties and effect of
      hypothermia on the natural progression of the disease are not known, and a only
      small number of papers has been published with results from these studies. Mild
      hypothermia at 34 degrees C was induced in six patients with hemorrhagic stroke
      in the first 48 h after presentation, using an intravascular catheter placed in
      the inferior vena cava. The hypothermia was induced and maintained for 24 h
      followed by gradual rewarming. Another 18 patients with hemorrhagic stroke but
      not receiving hypothermia were then taken as the control group, and all patients
      were treated with standard stroke management. The patients were then followed up
      using the modified Rankin Scale (mRS) for 6 months and 1 year. There was a
      statistically significant improvement at 6 months and 1 year follow-up using the
      mRS score in the hypothermia group, indicating a possible beneficial effect of
      early therapeutic hypothermia in the management of acute hemorrhagic stroke.
      However, a larger study is needed in order to confirm our finding.

PMID- 21725795
TI  - Use of intralesional tPA in spontaneous intracerebral hemorrhage: retrospective
      analysis.
AB  - INTRODUCTION: Neurosurgical treatment of spontaneous intracerebral hemorrhage
      (ICH) is controversial, with a lack of evidence-based guidelines contributing to
      the high variety of treatments. In our study we examine the outcome and
      complication from use of intralesional tissue plasminogen activator (IL tPA).
      METHOD: Patients who have been treated with IL tPA for spontaneous ICH were
      reviewed retrospectively. We compared clot sizes before and after tPA infusion,
      and outcome based on the modified Rankin score. RESULTS: Nine patients received
      IL tPA during the period 1999-2009. No immediate complications with use of IL tPA
      were found. There was a statistically significant volume reduction in clot sizes
      on computed tomography. Four patients recovered to independent functional status.
      Three patients were discharged to SNF, and two patients died as a result of ICH.
      Our results appear to demonstrate superior outcome to supportive management and
      no worse result than surgical management. CONCLUSION: It appears a subset of ICH
      patients benefits from use of IL tPA. This study demonstrates that IL tPA use is
      safe and has the potential to improve outcome compared to conservative management
      without the risk of surgical complications. Our patient size is small, and larger
      prospective studies are needed to provide solid guidelines for management of ICH.

PMID- 21725796
TI  - Endoscopic surgical treatment for pituitary apoplexy in three elderly patients
      over the age of 80.
AB  - OBJECTIVES: As the population continues to live longer, the diagnosis of
      pituitary adenoma-induced apoplexy becomes more common in the elderly. The
      standard treatment options for pituitary apoplexy are debatable. Although there
      is little information regarding the treatment of pituitary apoplexy in elderly
      patients, the optimal treatment needs to be determined for this age group. The
      current study examined the surgical treatment of pituitary apoplexy in three
      patients over the age of 80. CASE DESCRIPTION: Three patients over the age of 80
      with pituitary apoplexy were admitted to our hospital. Some symptoms caused by
      pituitary apoplexy, including decreased visual acuity, double vision and
      oculomotor paresis, had persisted for more than 14 days. Magnetic resonance
      imaging revealed suprasellar mass lesions extending into the cavernous sinus. The
      general condition of the patients was good, and we performed endoscopic
      transsphenoidal surgery in each of these cases. The masses were removed, and the
      histological findings were diagnosed as non-functioning pituitary adenoma with
      presence of hemorrhagic or ischemic necrosis. Perioperative courses and general
      conditions were good, and the neurological deficits of each patient improved
      immediately. CONCLUSIONS: Endoscopic transsphenoidal surgery has the advantage of
      visualization of the structures surrounding the pituitary gland. Moreover, the
      complication rate is relatively low because stress on the pituitary gland can be
      reduced by using this procedure. Even in patients over 80 years of age during the
      subacute phase, endoscopic surgical management is a good treatment candidate for
      pituitary apoplexy with mass lesion extension into the cavernous sinus.

PMID- 21725797
TI  - Proton pump inhibitor prophylaxis increases the risk of nosocomial pneumonia in
      patients with an intracerebral hemorrhagic stroke.
AB  - BACKGROUND: Stress-related mucosal damage is an erosive process of the gastric
      lining resulting from abnormally high physiologic demands. To avoid the morbidity
      and mortality associated with significant bleeding from the damage, prophylaxis
      with an acid suppression medication is given. This is especially common in stroke
      victims. Recent studies have suggested a link between acid suppression therapy
      and nosocomial pneumonia, specifically implicating proton pump inhibitors (PPI),
      a potent acid suppression medication, as the culprit. In this retrospective
      study, we reviewed the medical records of admitted intracerebral hemorrhage (ICH)
      patients and determined if there is a link between PPI prophylaxis and nosocomial
      pneumonia in our ICH population. MATERIALS AND METHODS: Medical records of 200
      ICH patients admitted to the First Affiliated Hospital of Chongqing Medical
      University were reviewed from January 1, 2008 to October 31, 2009. PPIs were the
      only accepted form of acid suppression therapy. In all, 95 patients were given
      PPI prophylaxis, whereas 105 patients did not receive any form of acid
      suppression. RESULTS: The unadjusted incidence rate of pneumonia in the PPI
      prophylactic group was 23.2%, and 10.5% in patients not having received
      prophylaxis. Additionally, patients treated with PPI prophylaxis were more likely
      to be critically ill, defined by an increase in conscious disturbance and
      dependency on mechanical ventilation and/or a nasogastric tube. CONCLUSION: The
      use of a PPI as a prophylactic treatment against stress-related mucosal damage
      was associated with a higher occurrence of nosocomial pneumonia in our ICH
      population. This study suggests the need for further research investigating the
      use of PPI prophylaxis in ICH patients and the possibility of using alternate
      acid suppression therapeutic modalities.

PMID- 21725799
TI  - Validation of quinidine as a probe substrate for the in vitro P-gp inhibition
      assay in Caco-2 cell monolayer.
AB  - Although quinidine has been recommended as a probe substrate for the P-gp
      inhibition assay using Caco-2 cell monolayer, it has not been studied widely in
      the in vitro system. In the present investigation, in vitro permeability studies
      using Caco-2 cell monolayer were carried out in order to optimize and validate
      quinidine as a P-gp probe substrate. In bi-directional Caco-2 assay across
      different passages, a good efflux ratio of more than ten was consistently
      obtained at 100 nM donor concentration of quinidine. Quinidine was found to have
      a good mass balance in the Caco-2 system. The inhibitory potencies of known P-gp
      inhibitors viz verapamil, ketoconazole, tacrolimus and cyclosporine A, determined
      over a wide concentration range, showed low apparent IC(50) values. Overall,
      quinidine was found to be a good probe substrate for routine use to assess the in
      vitro inhibitory potency of NCEs on Pgp-mediated transport.

PMID- 21725800
TI  - Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor
      clinical outcome in medulloblastoma.
AB  - Aberrant expression of stem cell-related genes in tumors may confer more
      primitive and aggressive traits affecting clinical outcome. Here, we investigated
      expression and prognostic value of the neural stem cell marker CD133, as well as
      of the pluripotency genes LIN28 and OCT4 in 37 samples of pediatric
      medulloblastoma, the most common and challenging type of embryonal tumor. While
      most medulloblastoma samples expressed CD133 and LIN28, OCT4 expression was found
      to be more sporadic, with detectable levels occurring in 48% of tumors.
      Expression levels of OCT4, but not CD133 or LIN28, were significantly correlated
      with shorter survival (P <= 0.0001). Median survival time of patients with tumors
      hyperexpressing OCT4 and tumors displaying low/undetectable OCT4 expression were
      6 and 153 months, respectively. More importantly, when patients were clinically
      stratified according to their risk of tumor recurrence, positive OCT4 expression
      in primary tumor specimens could discriminate patients classified as average risk
      but which further deceased within 5 years of diagnosis (median survival time of
      28 months), a poor clinical outcome typical of high risk patients. Our findings
      reveal a previously unknown prognostic value for OCT4 expression status in
      medulloblastoma, which might be used as a further indicator of poor survival and
      aid postoperative treatment selection, with a particular potential benefit for
      clinically average risk patients.

PMID- 21725801
TI  - Prolonged temozolomide for treatment of glioblastoma: preliminary clinical
      results and prognostic value of p53 overexpression.
AB  - We report retrospective data on the feasibility and efficacy of prolonging
      adjuvant temozolomide (TMZ) more than 6 months after chemoradiotherapy completion
      in patients with glioblastoma (GBM). Molecular prognostic factors were assessed.
      Data from 46 patients were reviewed. Patients received postoperative irradiation,
      60 Gy in 30 fractions, combined with concurrent TMZ, 75 mg/m(2). Four weeks
      later, adjuvant TMZ was prescribed, 150-200 mg/m(2) for a total of 24 cycles
      unless there was progression or toxicity. Tumor samples were tested for the
      following prognostic factors: EGFR overexpression, 1p19q deletion, p53
      overexpression and proliferation index. Overall survival (OS) was 84.8% at 6
      months, 54.3% at 12 months, 26.1% at 18 months, and 21.7% at 24 months.
      Progression-free survival (PFS) was 73.9% at 6 months, 34.8% at 12 months, 15.2%
      at 18 months and 10.4% at 24 months. In the adjuvant phase, no treatment
      disruption for toxicity was necessary but eight patients required dose adaptation
      because of side effects. No significant molecular prognostic factor was evidenced
      for OS. We found that p53 overexpression was the only significant prognostic
      factor for PFS, with a median PFS of 9.3 months versus 7 months for patients
      without p53 overexpression (P = 0.031). This study suggests that delivering
      adjuvant TMZ therapy for more than 6 months is feasible in patients with GBM.
      Efficacy data warrant further prospective assessment with the focus on molecular
      prognostic factors, such as p53 overexpression, which was found to be the only
      significant molecular prognostic factor for outcome.

PMID- 21725802
TI  - MGMT expression and promoter methylation status may depend on the site of
      surgical sample collection within glioblastoma: a possible pitfall in
      stratification of patients?
AB  - We recently described a three-layer concentric model of a glioblastoma (GBM)
      related to a specific distribution of molecular and phenotypic characteristics
      driven by the intratumoral hypoxic gradient in which the cancer stem cells niche
      is located in the hypoxic necrotic core of the tumour. The purpose of this study
      was to investigate the relationship between O(6)-methylguanine-DNA
      methyltransferase (MGMT) promoter methylation status and MGMT expression in GBM
      samples collected according to the three-layer concentric model. Multiple tissue
      samples were obtained, by means of image-guided surgery, from the three
      concentric layers of newly diagnosed GBM. Two samples from each layer were
      collected from 12 patients (total 72 samples). Immunohistochemical analysis was
      performed on formalin-fixed paraffin-embedded tissue samples. The methylation
      status of the MGMT promoter was determined by methylation-specific polymerase
      chain-reaction analysis. In all tumours, MGMT protein expression decreased
      progressively from the inner to the outer layer, and methylation of the MGMT
      promoter was unrelated to tumour layer. In particular, the MGMT promoter was
      unmethylated in all layers in 41.7% of tumours, methylated in all layers in 25%,
      and variably methylated in the three layers in 33.3%. We recorded concordance
      between MGMT expression and MGMT promoter methylation status within the GBM in
      only 58.8% of the samples collected. Our data suggest that both MGMT expression
      and promoter methylation data may be variable throughout GBM and that they may,
      consequently, depend on the site of surgical sample collection, even in the same
      patient. However, whereas MGMT expression is pre-operatively predictable when
      sampling is performed according to the three-layer concentric model, MGMT
      promoter methylation is not. These results must be considered when sample
      collection is performed for assessment of MGMT data.

PMID- 21725803
TI  - Integrating functional MRI information into conventional 3D radiotherapy planning
      of CNS tumors. Is it worth it?
AB  - The purpose of our study was to examine the potential benefits of integrating
      functional MRI (fMRI) information into the 3D-based planning process for central
      nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2009, ten
      patients with astrocytoma (both low and high-grade histological type) were
      enrolled in this study. Before the planning process, conventional CT planning,
      postoperative MR, and individual functional MRI examinations were conducted. For
      the functional MRI examination four types of conventional stimuli were applied:
      acoustic, visual, somatosensory, and numeric. To examine the potential benefits
      of using fMRI-based information, three different types of theoretical planning
      were applied and compared: 3D conformal plan without fMRI information, 3D
      conformal plan with fMRI information, and IMRT plan with fMRI information. DVH
      analysis and the NTCP model were used for plan comparison. When comparing
      planning methods, distance-related subgroups were generated and studied. By using
      the additional fMRI information, a significantly higher sparing effect can be
      achieved on these ORs (both with conventional 3D-based planning and IMRT). In
      cases when the OR-PTV distance is less than 1 cm, IMRT seems to be a
      significantly better choice than conventional 3D-based techniques. IMRT also has
      an additional sparing effect on the optic tract and brainstem, especially for
      locations close to the midline. Our results demonstrated that using fMRI
      information in conventional 3D-based treatment planning has the potential benefit
      of significant dose reduction for the critical organs, with no compromise in PTV
      coverage even when using conventional 3D planning. fMRI can be widely used in low
      grade cases (long life expectancy, lower acute and late toxicity) and also in
      cases with high-grade astrocytomas or distant metastases (higher dose to PTV with
      better sparing of risk organs). In cases when the OR-PTV distance is less than 1
      cm, IMRT should be the choice of treatment for a higher sparing effect on
      functional active areas. Longer imaging and clinical follow up are needed to
      confirm the real sparing effect on these functional areas.

PMID- 21725804
TI  - Trimebutine as a modulator of gastrointestinal motility.
AB  - Trimebutine has been used for treatment of both hypermotility and hypomotility
      disorders of the gastrointestinal (GI) tract, such as irritable bowel syndrome.
      In this issue, Tan et al. (2011) examined the concentration-dependent dual
      effects of trimebutine on colonic motility in guinea pig. The authors suggested
      that trimebutine attenuated colonic motility mainly through the inhibition of L
      type Ca(2+) channels at higher concentrations, whereas, at lower concentrations,
      it depolarized membrane potentials by reducing BK(ca) currents, resulting in the
      enhancement of the muscle contractions. Trimebutine might be a plausible
      modulator of GI motility, which gives an insight in developing new prokinetic
      agents. Further studies to elucidate the effects of trimebutine on the
      interstitial cells of Cajal, the pacemaker in GI muscles would promote the
      therapeutic benefits as a GI modulator.

PMID- 21725805
TI  - Triterpenoid saponins from the seeds of Caragana microphylla.
AB  - Two new triterpenoid saponins, namely caraganoside C (1) and caraganoside D (2),
      were isolated from the seeds of Caragana microphylla. Their structures were
      elucidated on the basis of spectroscopic analyses, including homo- and hetero
      nuclear correlation NMR experiments (COSY, HSQC and HMBC). Both 1 and 2 exhibited
      moderate inhibitory activity against NO production in LPS-stimulated RAW264.7
      cells with IC(50) values of 26.4 MUM and 32.2 MUM, respectively. In addition, 1
      showed weak cytotoxicity against MCF-7, HL-60, HCT116, and A549 cell lines.

PMID- 21725806
TI  - ent-Abietane diterpenoids from Isodon xerophilus.
AB  - Three new ent-abietanoids, named xerophilusins XIV-XVI, and four known analogues,
      as well as four known chemical constituents were isolated from the leaves of
      Isodon xerophilus. Their structures were elucidated by extensive spectroscopic
      studies, and comparison with literature data. In addition, the cytotoxic activity
      of the ent-abietanoids against chronic myelogenous leukemia (K562), stomach
      adenocarcinoma (MKN45), and hepatocellular carcinoma (HepG2) human cell lines was
      investigated and no activities were observed.

PMID- 21725807
TI  - A new phenolic compound with anticancer activity from the wood of Millettia
      leucantha.
AB  - A new phenolic compound, 1-(3-hydroxy-4-methoxyphenyl)-3-(2,4-dihydroxy-5
      methoxyphenyl) propan-1-ol, named as millettinol (1), along with six known
      compounds, medicarpin (2), 4-hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (3),
      5,4'-dihydroxy-7,8-dimethoxyisoflavone (4), physcion (5), (R)-(-)-mellein (6) and
      isoliquiritigenin (7), were isolated from the wood of Millettia leucantha. The
      structures of the compounds were determined by an analysis of their spectroscopic
      data. Some of the isolates were tested for anticancer activity. Compound 1
      exhibited strong cytotoxicity against the BCA-1 tumor cell lines with an IC(50) =
      3.44 MUg/mL.

PMID- 21725808
TI  - Synthesis, characterization, and antihyperglycemic activity of novel oxazolidine
      derivatives.
AB  - A number of compounds have been prepared in order to improve pharmacological
      roles of antihyperglycemic activity. In the present paper, a series of 3-benzyl-2
      (4'-substituted phenyl)-4(5H)-(4"-nitrophenyl amino)-1,3-oxazolidines (6a-e) were
      tested against hyperglycemia. Their antihyperglycemic activity was evaluated by
      streptozotocin (STZ) and sucrose-loaded (SLM) models. Compounds 6a, b, c, d, and
      e displayed significant reductions in blood glucose in the streptozotocin and
      sucrose loaded rat models. The purity of the synthesized compounds was
      characterized by means of IR, (1)H-NMR, mass spectral and elemental analysis.

PMID- 21725809
TI  - Bioassay-guided isolation of a novel protein with antitumor activity from
      Trachyrhamphus serratus (Syngnathidae).
AB  - A novel protein with antitumor activity, Hailongin, was purified from the aqueous
      extract of the whole body of Trachyrhamphus serratus, which is commonly used in
      traditional Chinese medicine, by bioassay-guided fractionation. Hailongin
      exhibited strong inhibition of proliferation of the tested human cell lines, such
      as A549, HeLa, LoVo and CCRF-CEM. The IC(50) values of Hailongin ranged from 5.4
      to 25.7 MU/mL. An in vivo study showed that the growth of implanted S-180 solid
      tumors in mice was significantly inhibited by Hailongin treatment, while the
      immunological function of the tumor-bearing mice was enhanced. The molecular
      weight and the isoelectric point of Hailongin were 57.074 kDa (by MALDI-TOF-MS)
      and 6.2 (by isoelectric focusing-polyacrylamide gel electrophoresis),
      respectively. Seventeen amino acids were identified in Hailongin. The acidic
      amino acids accounted for the majority of Hailongin's amino acid composition. The
      N-terminal amino acid sequence of Hailongin was determined to be
      IVPYSHNAGNKGLTQMR and showed no significant homology with known proteins.

PMID- 21725810
TI  - Nidurufin as a new cell cycle inhibitor from marine-derived fungus Penicillium
      flavidorsum SHK1-27.
AB  - A new cell cycle inhibitor, nidurufin (1), was isolated from the marine-derived
      fungus Penicillium flavidorsum SHK1-27. An evaluation of antitumor activity
      indicated that 1 induced in vitro cell cycle arrest at G(2)/M transition in the
      K562 cell line in a concentration and time dependent manner, with an IC(50) value
      of 12.6 M.

PMID- 21725811
TI  - Aromatic compounds from the halotolerant fungal strain of Wallemia sebi PXP-89 in
      a hypersaline medium.
AB  - A new cyclopentanopyridine alkaloid, 3-hydroxy-5-methyl-5,6-dihydro-7H
      cyclopenta[b]pyridin-7-one (1), together with 11 known aromatic compounds were
      isolated from the secondary metabolites of the halotolerant fungal strain
      Wallemia sebi PXP-89 in 10% NaCl. Their structures including the absolute
      configurations of (2S,3S)-1-(4-hydroxyphenyl)butane-2,3-diol (2), (2R,3S)-1-(4
      hydroxyphenyl)butane-2,3-diol (3), and (S)-3-hydroxy-4-(4-hydroxyphenyl)-2-one
      (4) were elucidated by spectroscopic analysis and a modified Mosher's method.
      Compound 1 exhibited antimicrobial activity against Enterobacter aerogenes with a
      MIC of 76.7 MUM. The absolute configurations of compounds 2-4 were determined for
      the first time.

PMID- 21725812
TI  - Inhibition of nitric oxide production in RAW 264.7 macrophages by diterpenoids
      from Phellinus pini.
AB  - 8,14-labdadien-13-ol (1) and dehydroabietic acid (2) were isolated from the fruit
      body of Phellinus pini. Elucidation of their structures was based on
      spectroscopic methods including IR, MS, and NMR (1D and 2D). Two compounds were
      screened for their ability to inhibit NO production in LPS-activated RAW 264.7
      cells. Compounds 1 and 2 at 30 MUM and 50 MUM, respectively, inhibited NO
      production in activated macrophages.

PMID- 21725813
TI  - An investigation of formulation factors affecting feasibility of alginate
      chitosan microparticles for oral delivery of naproxen.
AB  - In the present work we investigated the feasibility of chitosan treated Ca
      alginate microparticles for delivery of naproxen in lower parts of GIT and
      evaluated influence of formulation factors on their physicochemical
      characteristics and drug release profiles. Investigated factors were drug/polymer
      ratio, chitosan molecular weight, chitosan concentration in hardening medium, and
      hardening time. Sixteen microparticle formulations were prepared utilizing 24
      full factorial design (each factor was varied at two levels). Microparticles size
      varied between 262.3 +/- 14.9 and 358.4 +/- 21.7 MUm with slightly deformed
      spherical shape. Low naproxen solubility and rapid reaction of ionotropic
      gelation resulted in high encapsulation efficiency (> 75.19%). Under conditions
      mimicking those in the stomach, after two hours, less than 6.18% of naproxen was
      released. Significant influence of all investigated factors on drug release rate
      was observed in simulated small intestinal fluid. Furthermore, experimental
      design analysis revealed that chitosan molecular weight and its concentration had
      the most pronounced effect on naproxen release. Release data kinetics indicated
      predominant influence of a pH-dependent relaxation mechanism on drug release from
      microparticles.

PMID- 21725814
TI  - Evaluation of mechanical and rheological properties of metronidazole gel as local
      delivery system.
AB  - Rosacea is a chronic multifactorial vascular skin disorder that affects about 10
      percent of the general population. Metronidazole is an effective antibiotic in
      the treatment of moderate-to severe rosacea. Metronidazole is a suitable drug in
      cases of resistance to tetracycline or erythromycin, but it has also been shown
      that oral metronidazole may increase the side effects (e.g., peripheral
      neuropathy). Oral metronidazole should not be used for more than three months,
      and hence topical metronidazole gel is the best therapeutic choice in rosacea
      (especially during pregnancy). This study examined the mechanical (adhesiveness,
      cohesiveness, extrudability, spreadability, homogeneity) and rheological
      (viscosity), skin irritant and drug release properties of different metronidazole
      gel formulations that contain anionic emulsifying wax, glycerin and lactic acid
      in different proportions. The release studies were conducted using Franz
      diffusion cells and Silastic membrane as a barrier. The results indicated that
      gel compressibility, hardness, and adhesiveness, are the factors that influence
      the ease of gel removal from the container, ease of gel application onto the
      mucosal membrane, and gel bioadhesion. The findings showed that there exists a
      strong negative correlation between the spreadability of a formulation and its
      cohesiveness, the spreadability of a formulation is inversely proportional to its
      cohesiveness. However, sorbitol solution (70%) concentration was not
      significantly correlated with drug release. In addition, drug release was
      significantly reduced as the concentration of anionic emulsifying wax increased
      and the concentration of lactic acid decreased. The maximum metronidazole release
      was achieved at a pH of 4-6. Data obtained from in vitro release studies were
      fitted to various kinetic models and high correlation was obtained in the Higuchi
      and first order models. The results showed that all the gel formulations showed
      good extrudability, viscosity, cohesiveness, homogeneity and spreadability.

PMID- 21725815
TI  - Encapsulation, pharmacokinetics and tissue distribution of interferon alpha-2b
      liposomes after intramuscular injection to rats.
AB  - The aim of the present study was to investigate the effect of liposome
      encapsulation and liposome-size on the in vivo pharmacokinetics of interferon
      alpha-2b (IFNalpha-2b) following i.m. administration to rats, and whether there
      was any liver-targeting of these liposomes. Since liposomes of different sizes
      can be obtained by homogenization, the effect of homogenization on the IFNalpha
      2b activity was also investigated. The pharmacokinetics of IFNalpha-2b solution
      (12.8 MUg/kg) and IFNalpha-2b prepared in liposomes, including three mean sizes
      of 172 nm (12.2 MUg/kg), 113 nm (44.2, 11.0, and 2.8 MUg/kg, respectively), and
      82 nm (13.1MUg/kg), were studied after a single i.m. dose to rats. Compared to a
      solution of IFNalpha-2b. administration of liposomal IFNalpha-2b resulted in a
      significantly prolonged t(max), the apparent elimination half life (t(1/2beta))
      was 2.3 times longer, both AUC(0-infinity) and MRT(0-infinity) were also clearly
      enhanced and greater accumulation was obtained in the liver (p < 0.05). The AUC(0
      infinity) increased proportionally to the administered dose of IFNalpha-2b
      liposomes. Moreover, the size of liposomes ranging from 82 nm to 172 nm had no
      significant difference on the pharmacokinetic behavior in vivo (p > 0.05). In
      sum, compared with the free form, IFNalpha-2b encapsulated in liposomes can alter
      strikingly the pharmacokinetics properties following i.m. injection and if a
      liposomal size ranging from 82 nm to 172 nm was used, consistent pharmacokinetic
      behaviors of IFNalpha-2b was exhibited. The liposomal formulation apparently
      targeted the liver, offering a potential advantage for hepatitis B treatment.

PMID- 21725816
TI  - Preparation and physicochemical characterizations of tanshinone IIA solid
      dispersion.
AB  - This investigation describes a novel approach to prepare solid dispersions of
      tanshinone IIA using a laboratory-scale planetary ball mill. Poloxamer 188 was
      employed as the surfactant carrier to improve the solubility and dissolution of
      the poorly soluble drug, tanshinone IIA. Solubility and dissolution were
      evaluated compared to the corresponding physical mixtures and pure drug.
      Furthermore, the physicochemical properties of the solid dispersions were
      investigated using scanning electron microscopy, powder X-ray diffraction,
      differential scanning calorimetry, Fourier transform infrared spectroscopy and
      ultraviolet spectrophotometry. The solid dispersion significantly enhanced drug
      solubility and dissolution compared with pure drug and the physical mixtures.
      Scanning electron microscopy, powder X-ray diffraction, differential scanning
      calorimetry and Fourier transform infrared spectroscopy analyses of tanshinone
      IIA/poloxamer 188 system confirmed that there were intermolecular interactions
      between tanshinone IIA and poloxamer 188 and no conversion to crystalline
      material. Tanshinone IIA existed in a microcrystalline form in the system. These
      results suggested that improvement of the dissolution rate could be correlated to
      the formation of a eutectic mixture between the drug and the carrier. After 60
      days the solid dispersion samples were chemically and physically stable. The
      present studies indicated that the planetary ball mill technique could be
      considered as a novel and efficient method to prepare solid dispersion
      formulations.

PMID- 21725817
TI  - Species classification and quality assessment of Chaihu (Radix Bupleuri) based on
      high-performance liquid chromatographic fingerprint and combined chemometrics
      methods.
AB  - A high-performance liquid chromatographic (HPLC) method was established to
      analyze 36 Chaihu (Radix Bupleuri) samples collected from three species
      (Bupleurum chinense DC., B. scorzonerifolium Willd. and B. smithii Wolff.).
      Addition of trifluoroacetic acid into the mobile phase resulted in fingerprint
      chromatograms with stable baselines. There were thirty-two characteristic peaks
      in the standard fingerprint of B. chinense DC. Different recognition pattern
      methods, including similarity analysis (SA), hierarchical cluster analysis (HCA),
      principal component analysis (PCA) and partial least squares-discrimination
      analysis (PLS-DA) were utilized to analyze the 36 samples based on the contents
      of chemical constituents. Consistent results from SA, HCA and PCA analysis
      illustrated the rationalisation for why B. smithii Wolff. was not quoted in the
      Chinese Pharmacopoeia and classified samples were in agreement with their
      species. PLS-DA loading plots showed the chemical markers which had the most
      influences on the separation among different species. However, SA, HCA and PCA
      could not differentiate between wild and cultivated B. chinense DC. as well as
      between samples from different provinces. HPLC fingerprint in combination with
      chemometric techniques provided a very flexible and reliable method for
      homogeneity evaluation and quality assessment of traditional Chinese medicine.

PMID- 21725818
TI  - Rhododendrin, an analgesic/anti-inflammatory arylbutanoid glycoside, from the
      leaves of Rhododendron aureum.
AB  - To identify an analgesic/anti-inflammatory component from the leaves of
      Rhododendron aureum (Ericaceae), phytochemical isolation and pharmacological
      assays (writhing assays and vascular permeability assay for analgesic action in
      mice; carrageenan-induced paw edemaand TPA-induced ear edema assays of anti
      inflammatory action in rats) were performed. Four compounds were isolated from
      the active fraction (BuOH fraction) by silica gel column chromatography and
      identified as (-)-rhododendrol, (-)-rhododendrin, avicularin and hyperoside by
      spectroscopic methods. Rhododendrin, the main compound of the BuOH fraction,
      exhibited significant analgesic actions in mice and anti-inflammatory actions in
      rats. This compound accounted for 3.1% of the MeOH extract and 0.48% of dried
      leaves, respectively, on HPLC analysis. These results suggest that rhododendrin
      is the major biologically active substance in the leaves of R. aureum with
      analgesic/anti-inflammatory activity.

PMID- 21725819
TI  - Effects of trimebutine maleate on colonic motility through Ca2+-activated K+
      channels and L-type Ca2+ channels.
AB  - The effects of trimebutine maleate (TM) on spontaneous contractions of colonic
      longitudinal muscle were investigated in guinea pigs. The contractile responses
      of smooth muscle strips were recorded by an isometric force transducer. Membrane
      and action potentials were detected by an intracellular microelectrode technique.
      The whole-cell patch clamp recording technique was used to record the changes in
      large conductance Ca(2+)-activated K(+) (BK(ca)) and L-type Ca(2+) currents in
      colonic smooth muscle cells. At high concentrations (30, 100, and 300 MUM), TM
      inhibited the amplitude of spontaneous contractions. At low concentrations (1 and
      10 MUM), TM attenuated the frequency and tone of smooth muscle strips, whereas TM
      had no influence on the amplitude of spontaneous contractions. TM depolarized the
      membrane potentials, but decreased the amplitude and frequency of action
      potentials at high concentrations. TM inhibited BK(ca) and L-type Ca(2+) currents
      in a dose-dependent manner. In the presence of the BK(ca) channel opener, NS1619,
      TM also inhibited BK(ca) currents. Bayk8644, a L-type Ca(2+) channel opener,
      increased L-type Ca(2+) currents. This augmentation was also attenuated by TM.
      These results suggest that TM attenuates intestinal motility through inhibition
      of L-type Ca(2+) currents, and depolarizes membrane potentials by reducing BK(ca)
      currents. Thus, TM may be a multiple-ion channel regulator in the
      gastrointestinal tract.

PMID- 21725820
TI  - Inhibition of tumor growth by recombinant adenovirus containing human lactoferrin
      through inducing tumor cell apoptosis in mice bearing EMT6 breast cancer.
AB  - Human lactoferrin (hLTF), an 80-kDa iron-binding glycoprotein, has antitumor
      activity. In this study, a recombinant adenovirus containing the human
      lactoferrin cDNA (ad-rhLTF) was constructed and its effect on tumor growth was
      investigated in mice bearing EMT6 breast cancer. Ad-rhLTF was injected seven
      times within 14 days into the tumor site at two concentrations (10(8) and 5 *
      10(8) pfu/mL) in mice bearing EMT6 breast cancer. Injected ad-rhLTF had
      considerable cytotoxicity on mice breast cancer, and significantly reducing the
      weight of tumor produced and increasing the tumor inhibition rate up to 52.64%.
      The presence of apoptotic cells was confirmed using TUNEL staining and flow
      cytometry assays. At the same time, RTPCR and Western blot analyses demonstrated
      that ad-rhLTF also decreased expression of Bcl-2 and increased Bax and caspase 3
      expressions. Therefore, we conclude that ad-rhLTF inhibits tumor growth by
      inducing tumor cell apoptosis in mice with breast cancer by triggering the
      mitochondrial-dependent pathway and activation of caspase 3. The results indicate
      that ad-rhLTF might be a promising drug for breast cancer gene therapy.

PMID- 21725821
TI  - Effects of diosgenin on cell proliferation induced by IGF-1 in primary human
      thyrocytes.
AB  - Others and our previous studies showed that the increase of IGF-1 was involved in
      the formation of goiter. Our aim here was to evaluate the possible effects of
      diosgenin on cell proliferation induced by IGF-1 in primary human thyroid cells.
      The cells were treated with or without different concentrations of diosgenin in
      the present or absent of IGF-1 for 24, 48 and 72 h, respectively. Cell viability
      was determined by MTT, and cell proliferation was tested by EdU assay, and cell
      cycle analysis was performed by FACS. In addition, Cyclin D1 and B1 protein
      expression was tested by Western Blotting, respectively. We found that IGF-1
      promoted cell cycle progression to S phase and increased the primary human
      thyroid cells proliferation. Diosgenin decreased the protein expression of cyclin
      D1 and resulted in cell G(0)/G(1) arrest. Importantly, when the human thyrocytes
      were exposed to diosgenin in the present of IGF-1, the IGF-1 inducing
      proliferation was significantly decreased and the proportion of the cells in
      G(0)/G(1) phase was increased, while that of S phase was decreased. This study
      shows that diosgenin inhibited cell proliferation, caused G(0)/G(1) arrest, and
      could inhibit cell proliferation induced by IGF-1 in primary human thyroid cells.

PMID- 21725822
TI  - Inhibition of bone resorption by econazole in rat osteoclast-like cells through
      suppressing TRPV5.
AB  - Osteoclasts are primary bone resorption cells and intervention in osteoclast
      activation is considered an effective therapeutic approach to treatment of bone
      diseases involving osteoclasts. TRPV5 was detected in osteoclasts and it has been
      thought to take part in the transportation of the degraded calcium in the
      resorption lacuna, which is essential for bone resorption. The aim of the present
      study was to examine the effects of a modulator of calcium dynamics, econazole,
      on the expression of TRPV5 and bone resorption activity in rat osteoclast-like
      cells (OLCs). OLCs were obtained by co-culturing rat bone marrow cells with
      osteoblasts and then culturing with different concentrations of econazole (0.01,
      0.1, 1.0, 10.0 MUmol/L). Cell counting and staining protocols were used to
      determine whether econazole influenced the survival of OLCs. Expression of TRPV5
      in response to econazole treatment was assessed by western blotting. Bone
      resorption activity of OLCs was determined by measuring the resorption area of
      dentin slices with a microscope and a digital image analysis system.
      Additionally, Ca(2+) inside OLCs was tested. We found that econazole inhibited
      expression of TRPV5 in a dose dependent manner while it had no influence on the
      survival of OLCs and it therefore inhibited bone resorption activity in rat OLCs.
      Ca(2+) inside OLCs increased, suggesting a limited compensatory mechanism to make
      up for inhibition of TRPV5 effects.

PMID- 21725823
TI  - Loss of contraction force in dermal fibroblasts with aging due to decreases in
      myosin light chain phosphorylation enzymes.
AB  - Although there have been many reports about the relationship between force
      generation by skeletal muscles and aging, no study has investigated the
      relationship between contraction forces generated by non-muscle cells and aging.
      In this study, we examined that relationship using fibroblast populating collagen
      gels and a contraction force detecting system. Fibroblasts at passages 5 to 7
      were used as the young group and those at passages 17 to 19 were used as the aged
      group. The contraction force induced by thrombin or lysophosphatidic acid
      significantly decreased with age. The expression of myosin light chain kinase
      (MLCK) and two types of Rho kinases (Rock-1 and Rock-2) decreased with age, but
      the expression of Rho A and myosin phosphatase (MPPase) did not change at all.
      The expression of myosin light chain 20k (MLC(20)) depended on the donor
      fibroblasts. Fibroblasts from young or aged hairless mice showed similar age
      dependent results. Taken together, our data suggest that decreased expressions of
      MLCK and Rho kinase are critical for loss of force generation by fibroblasts with
      aging, which suggests new mechanisms of functional deficiencies due to aging.

PMID- 21725824
TI  - Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal
      oxygen-glucose deprivation in cortical neurons in vitro.
AB  - Ischemic preconditioning can provide protection to neurons from subsequent lethal
      ischemia. The molecular mechanisms of neuronal ischemic tolerance, however, are
      still not well-known. The present study, therefore, examined the role of MAPK and
      PI3K/Akt pathways in ischemic tolerance induced by preconditioning with sublethal
      oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. Ischemic
      tolerance was simulated by preconditioning of the neurons with sublethal 1-h OGD
      imposed 12 h before lethal 3-h OGD. The time-course studies of relative
      phosphorylation and expression levels of ERK1/2, JNK and p38 MAPK showed lack of
      their involvement in ischemic tolerance. However, there were significant
      increases in Akt phosphorylation levels during the reperfusion period following
      preconditioned lethal OGD. In addition, Bcl-2 associated death promoter (Bad) and
      GSK-3beta were also found to be inactivated during that reperfusion period.
      Finally, treatment with an inhibitor of PI3K, wortmannin, applied from 15 min
      before and during lethal OGD abolished not only the preconditioning-induced
      neuroprotection but also the Akt activation. Concomitant with blockade of the Akt
      activation, PI3K inhibition also resulted in activation of Bad and GSK-3beta. The
      results suggest that ischemic tolerance induced by sublethal OGD preconditioning
      is primarily mediated through activation of the PI3K/Akt pathway, but not the
      MAPK pathway, in rat cortical neurons.

PMID- 21725826
TI  - Amelioration of oral mucositis pain by NASA near-infrared light-emitting diodes
      in bone marrow transplant patients.
AB  - PURPOSE: This study seeks to investigate the use of extra-orally applied near
      infrared phototherapy for the reduction of oral pain secondary to chemotherapy-
      and radiation therapy-induced mucositis in adult and pediatric hematopoietic stem
      cell transplant (HSCT) patients. METHODS: Eighty HSCT patients were divided into
      regular (R) and low (L) risk groups, then to experimental (E) and placebo (P)
      groups, resulting in four groups (ER, EL, PR, PL). Experimental subjects received
      670 (+/- 10) nm gallium-aluminum-arsinide light-emitting diode device for 80 s at
      ~50 mW/cm(2) energy density and power exposure of 4 J/cm(2). Placebo patients
      received the same procedures, but with a placebo phototherapy (identical device
      but <5 mW/cm(2) energy density). Patients received their respective light therapy
      once per day starting on the day of the HSCT (day 0) and continued through day
      +14. Blinded evaluators examined the patients three times per week and scored
      their oral tissues and patient-reported pain assessments at each evaluation
      utilizing the WHO, NCI-CTCAE, and OMAS scales. RESULTS: Analysis of the mean
      scores at each observation demonstrate that the extra-oral application of
      phototherapy resulted in a significant reduction in patient-reported pain between
      the ER and PR patients (p < 0.05) at day +14 when graded via the WHO criteria.
      The ER and EL patients were improved in almost all other categories and
      assessment scales, but the differences were not statistically significant.
      CONCLUSION: Phototherapy demonstrated a significant reduction in patient-reported
      pain as measured by the WHO criteria in this patient population included in this
      study. Improvement trends were noted in most other assessment measurements.

PMID- 21725827
TI  - Treatment referral before and after the introduction of the Liverpool Patients
      Concerns Inventory (PCI) into routine head and neck oncology outpatient clinics.
AB  - PURPOSE: Holistic needs assessment is a key recommendation in improving
      supportive and palliative care in adults with cancer. The Patients Concerns
      Inventory (PCI) is a holistic needs assessment tool designed for head and neck
      cancer survivors in outpatient setting. Routine screening of potential unmet
      needs in a clinic may result in increased onward referrals, thus placing a burden
      on existing healthcare services. The aim of this study was to compare the
      referral trends following consultation in the time periods before and after
      introduction of PCI in an oncology outpatient clinic. METHOD: A cross-sectional
      cohort of disease-free survivors of oral/oropharyngeal cancers of a single
      consultant was prospectively exposed to PCI from July 2007 to April 2009. The PCI
      is a self-completed questionnaire consisting of 55 items of patient needs/concern
      and a list of multidisciplinary professionals, whom patients may wish to talk to
      or be referred to. Retrospective analysis of referral patterns from clinic
      letters in two periods in the pre-PCI and post-PCI exposure was performed.
      Prospective analysis of consultations was performed to determine the outcome of
      PCI-highlighted items. RESULTS: There was no change in the prevalence of onward
      referral with the introduction of PCI, i.e. 21 referrals per 100 patients seen in
      outpatients. However, the proportion of referrals to oral rehabilitation and
      psychological support increased. Referrals to certain services, e.g. speech and
      language and dentistry, remained consistently in demand. Many PCI-highlighted
      needs were dealt in a clinic with by the consultant and/or other professionals
      during a multidisciplinary consultation. CONCLUSIONS: Routine use of PCI promotes
      target efficiency by directing and apportioning appropriate services to meet the
      needs for supportive care of head and neck cancer survivors.

PMID- 21725828
TI  - Recurrent brain tumour: the impact of illness on patient's life.
AB  - PURPOSE: Despite advances in therapies that offer improved survival rates,
      clinical course of brain tumours leads to a progressive functional deterioration
      in patients with modifications in their psychological reaction to the disease.
      Patients with brain tumours are rarely assessed for quality of life and
      psychological variables, and even fewer studies have assessed patients who have
      experienced a recurrence of brain tumours. Therefore, the aim of the present
      study is to investigate the patients with recurrent brain tumours and their
      reaction to the illness. METHOD: We enrolled 81 patients with recurrent CNS
      tumours. Karnofsky Performance Status scale (KPS) was used to evaluate functional
      status of patients; the multidimensional aspect of quality of life was assessed
      through "Functional Assessment of Cancer Therapy-Brain" (FACT-Br), "Hospital
      Anxiety and Depression Scale" and "Psychological Distress Inventory". These were
      all used as tests of psychological well-being. RESULTS: Distress and almost all
      mean FACT-Br subscale scores seemed to be significantly lower in patients, in
      comparison with normative data. Surprisingly, the emotional well-being mean score
      was significantly higher in our recurrence sample than in patients with brain
      tumours at first diagnosis. Anxiety seemed not to be influenced by a relapse
      diagnosis; instead, depression was higher and differed significantly from
      normative data. Low correlation between KPS and FACT-Br total and some sub-scores
      was found. CONCLUSIONS: Apparent dissociation between patients' judgment on their
      quality of life (bad except for emotional) and their reported distress (low) is
      the most intriguing finding, suggesting highly preserved coping strategies in the
      emotional sphere, despite intact judgment and disease awareness.

PMID- 21725829
TI  - Simultaneous determination of histamine and prostaglandin D2 using an LC-ESI
      MS/MS method with positive/negative ion-switching ionization modes: application
      to the study of anti-allergic flavonoids on the degranulation of KU812 cells.
AB  - A new method for simultaneous determination of histamine and prostaglandin D(2)
      (PGD(2)) by liquid chromatography-electrospray ionization tandem mass
      spectrometry operated in positive and negative ionization switching modes was
      developed and validated without a previous derivatization step. This method was
      used to measure histamine and PGD(2) release following degranulation of KU812
      human basophilic cells, using pyrazol and d(4)-PGD(2) as internal standards.
      Analyses were performed on a liquid chromatography system employing a Cosmosil
      5C(18) PAQ column and an isocratic elution with mixed solution of methanol-water
      (7:3, v/v) with 0.0015% trifluoroacetic acid at a flow rate of 0.2 mL/min. A
      triple-quadrupole mass spectrometer operating in selected reaction monitoring
      mode simultaneously monitored using the following transitions: positive m/z
      112/95 for histamine and negative m/z 351/271 for PGD(2). The retention times of
      histamine and pyrazol were 4.2 and 5.0 min, respectively. PGD(2) and d(4)-PGD(2)
      had retention times of 8.5 min. The limits of detection were 0.3 and 0.5 ng/mL
      for histamine and PGD(2), respectively. The relative standard deviations of the
      retention time and peak area for histamine were between 1.6% and 7.7%, and were
      1.2% and 7.8% for PGD(2). This method was used to evaluate the anti-allergic
      effects of 26 flavonoids and sodium cromoglicate which are first-line anti
      allergic drugs. Of these compounds, baicalein and morin were the most potent
      inhibitors.

PMID- 21725830
TI  - Quantification of the six major alpha-dicarbonyl contaminants in peritoneal
      dialysis fluids by UHPLC/DAD/MSMS.
AB  - During heat sterilization of peritoneal dialysis solutions, glucose is partially
      transformed into glucose degradation products (GDPs), which significantly reduce
      the biocompatibility of these medicinal products. Targeted alpha-dicarbonyl
      screening identified glyoxal, methylglyoxal, 3-deoxyglucosone, 3,4
      dideooxyglucosone-3-ene, glucosone, and 3-deoxygalactosone as the major six GDPs
      with alpha-dicarbonyl structure. In the present study, an ultra-high-performance
      liquid chromatography method was developed which allows the separation of all
      relevant alpha-dicarbonyl GDPs within a run time of 15 min after derivatization
      with o-phenylenediamine. Hyphenated diode array detection/tandem mass
      spectrometry detection provides very robust quantification and, at the same time,
      unequivocal peak confirmation. Systematic evaluation of the derivatization
      process resulted in an optimal derivatization period that provided maximal
      derivatization yield, minimal de novo formation (uncertainty range +/-5%), and
      maximal sample throughput. The limit of detection of the method ranged from 0.13
      to 0.19 MUM and the limit of quantification from 0.40 to 0.57 MUM. Relative
      standard deviations were below 5%, and recovery rates ranged between 91% and
      154%, dependent on the type and concentration of the analyte (in 87 out of 90
      samples, recovery rates were 100 +/- 15%). The method was then applied for the
      analysis of commercial peritoneal dialysis fluids (nine different product types,
      samples from three lots of each).

PMID- 21725831
TI  - What determines MALDI ion yields? A molecular dynamics study of ion loss
      mechanisms.
AB  - Ion recombination in matrix-assisted laser desorption/ionization (MALDI) is as
      important as any ion formation process in determining the quantity of ions
      observed but has received comparatively little attention. Molecular dynamics
      simulations are used here to investigate some models for recombination, including
      a Langevin-type model, a soft threshold model and a tunneling model. The latter
      was found to be superior due to its foundations in a widespread physical
      phenomenon, and its lack of excessive sensitivity to parameter choice. Tunneling
      recombination in the Marcus inverted region may be a major reason why MALDI is a
      viable analytical method, by allowing ion formation to exceed ion loss on the
      time scale of the plume expansion. Ion velocities, photoacoustic transients and
      pump-probe measurements might be used to investigate the role of recombination in
      different MALDI matrices, and to select new matrices.

PMID- 21725832
TI  - Development and validation of a selective HPLC-ESI-MS/MS method for the
      quantification of glyoxal and methylglyoxal in atmospheric aerosols (PM2.5).
AB  - This study concerns the development and validation of a complete method for the
      analysis of two highly reactive alpha-dicarbonyl compounds, glyoxal (Gly) and
      methylglyoxal (Mgly), in atmospheric fine particulate matter (PM(2.5)). Method
      development included optimization of sample preparation procedures, e.g., filter
      extraction, concentration of extracts, derivatization and solid-phase extraction
      (SPE) of derivatives, as well as reversed-phase liquid chromatography coupled to
      electrospray ion-trap mass spectrometry (HPLC-ESI-IT/MS/MS) measurement
      parameters. Selectivity of detection was enhanced using tandem mass spectrometric
      analysis in ESI positive ion mode via two multiple reaction monitoring channels,
      m/z 433 -> m/z 250 and m/z 419 -> m/z 236 for Mgly and Gly. Retention times were
      9.5 and 12.5 min for Gly- and Mgly-bis-hydrazone derivatives. Calibration ranged
      from 0.5 to 50 ng/mL. Inter-batch precision, expressed as relative standard
      deviation, was <15%. The method was shown to be unaffected by the sample matrix
      and to have recoveries of 100% and 60% for Gly and Mgly, respectively. Improved
      instrumental detection limits of 0.51 and 0.62 ng/mL for Gly and Mgly were
      achieved using a SPE method for the purification of 2,4-dinitrophenylhydrazine
      derivatization reagent solutions. This permitted the method to be used for
      analysis of filter samples obtained during a field study at the Taunus
      Observatory (mount Kleiner Feldberg, Germany). PM(2.5) concentrations ranged from
      0.81 to 1.18 ng/m(3) for Gly and from 0.83 to 1.92 ng/m(3) for Mgly. PM
      concentrations correlated to the concentration of NO with coefficients (R(2)) of
      0.67 (Gly) and 0.78 (Mgly).

PMID- 21725833
TI  - Spectral analysis of pharmaceutical formulations prepared according to ancient
      recipes in comparison with old museum remains.
AB  - A study of the composition of the remains of ancient ointments from museums was
      undertaken to enable understanding of the preparation techniques. Comparison of
      ancient recipes from different historical periods and spectroscopic
      characteristics of inorganic and/or organic remains recovered in museum vessels
      enabled preparation of ancient pharmaceutical-cosmetic formulations. Farmacopea
      Augustana by Occo was one the most important books studied for the 14
      formulations prepared in the laboratory. Three formulations are discussed in
      detail and raw materials and new preparations were proposed for ozone ageing. The
      most important micro Raman results are discussed. The spectra of the raw
      materials lipids, beeswax, and resins are discussed; beeswax and pig suet
      (axungia) Raman spectra were found to be similar, but different from those of the
      aged oils. SERS was applied to ancient ointments and galbanum and the Raman
      spectra are reported and discussed for the first time.

PMID- 21725834
TI  - Characterization of fresh and aged natural ingredients used in historical
      ointments by molecular spectroscopic techniques: IR, Raman and fluorescence.
AB  - Natural organic materials used to prepare pharmaceutical mixtures including
      ointments and balsams have been characterized by a combined non-destructive
      spectroscopic analytical approach. Three classes of materials which include
      vegetable oils (olive, almond and palm tree), gums (Arabic and Tragacanth) and
      beeswax are considered in this study according to their widespread use reported
      in ancient recipes. Micro-FTIR, micro-Raman and fluorescence spectroscopies have
      been applied to fresh and mildly thermally aged samples. Vibrational
      characterization of these organic compounds is reported together with tabulated
      frequencies, highlighting all spectral features and changes in spectra which
      occur following artificial aging. Synchronous fluorescence spectroscopy has been
      shown to be particularly useful for the assessment of changes in oils after
      aging; spectral difference between Tragacanth and Arabic gum could be due to
      variations in origin and processing of raw materials. Analysis of these materials
      using non-destructive spectroscopic techniques provided important analytical
      information which could be used to guide further study.

PMID- 21725835
TI  - Elevated eating disorder symptoms in women with a history of oral contraceptive
      side effects.
AB  - Previous research suggests a link between gonadal hormones and eating disorder
      symptomatology. This study examined the role of gonadal hormones and hormonal
      sensitivity in eating disorder (ED) symptoms by using oral contraceptive (OC)
      side effect history as an indicator of hormonal sensitivity. A questionnaire
      containing two scales of the Eating Disorder Inventory-2 and an OC side effect
      scale was completed by 174 healthy women who had used OCs. Histories of emotional
      and physical OC side effects were evaluated as predictors of body dissatisfaction
      and drive for thinness. Women with a history of negative OC side effects had
      higher levels of ED symptoms. After controlling for body mass index (BMI) and
      depression scores, OC side effect history remained a significant predictor of
      body dissatisfaction and drive for thinness. The experience of OC side effects
      may indicate a greater risk for increased eating disorder symptoms. The findings
      provide further support for a hormonal link to ED symptoms, as women who are more
      "sensitive" to exogenous gonadal hormones also experience more ED symptoms.

PMID- 21725836
TI  - Depression and anxiety among postpartum and adoptive mothers.
AB  - Similar to biological mothers during the postpartum period, women who adopt
      children experience increased stress and life changes that may put them at risk
      for developing depression and anxiety. The purpose of the current study was to
      compare levels of depression and anxiety symptoms between postpartum and adoptive
      women and, among adoptive women, to examine associations between specific
      stressors and depressive symptoms. Data from adoptive mothers (n = 147),
      recruited from Holt International, were compared to existing data from postpartum
      women (n = 147). Differences in the level of depression and anxiety symptoms as
      measured by the Inventory of Depression and Anxiety Symptoms among postpartum and
      adoptive women were examined. Associations between specific stressors and
      depressive symptoms were examined among adoptive mothers. Postpartum and adoptive
      women had comparable levels of depressive symptoms, but adoptive women reported
      greater well-being and less anxiety than postpartum women. Stressors (e.g., sleep
      deprivation, history of infertility, past psychological disorder, and less
      marital satisfaction) were all significantly associated with depressive symptoms
      among adoptive women. The level of depressive symptoms was not significantly
      different between the two groups. In contrast, adoptive women experienced
      significantly fewer symptoms of anxiety and experienced greater well-being.
      Additionally, adoptive mothers experienced more depressive symptoms during the
      year following adoption when the stressors were present. Thus, women with these
      characteristics should be routinely screened for depression and anxiety.

PMID- 21725837
TI  - Control of tick populations by spraying Metarhizium anisopliae conidia on cattle
      under field conditions.
AB  - Conidia of the entomopathogenic fungus, Metarhizium anisopliae, in oil/water
      formulation (1 * 10(8) conidia/ml) were sprayed at 3 weekly intervals on
      Rhipicephalus evertsi evertsi and Rhipicephalus (Boophilus) decoloratus ticks
      while feeding on Afrikana bulls grazing in paddocks for a period of 1 year. The
      fungus reduced the on-host tick populations by 83% 3 month after commencement of
      the experiment. The formulation by itself had only minimal effect on the tick
      population. Tick populations and fungal efficacy were highest at the peaks of
      rainfall and relative humidity or soon thereafter. Fed and unfed adult R. e.
      evertsi and R. (B.) decoloratus collected at the end of the experiment from the
      fungus-sprayed and from the control cattle and incubated in the laboratory
      exhibited a mortality of 93% in oil formulated conidia and 14% in oil control.
      The corresponding mortality in R. (B.) decoloratus was 100% in fungus and 11% in
      oil control. Ticks on the fungus-sprayed groups had significantly higher
      mortality (P < 0.05) than on the control groups. Furthermore, no significant
      difference (P < 0.05) was observed in fungus-induced mortality between the two
      tick species. Mortalities induced by Triton X-100 (0.05%), sunflower oil (20%)
      and water alone were low, suggesting that they were non-toxic to ticks at the
      concentrations used and no significant difference was observed among them. No
      physical or behavioral abnormalities were observed in the fungus-sprayed cattle
      at any time during the course of the experiment. All groups of cattle gained
      weights during the experimental period.

PMID- 21725838
TI  - Elevated serum IgG4 is associated with chronic antibiotic-refractory pouchitis.
AB  - BACKGROUND AND AIM: We recently reported mucosal infiltration of IgG4-expressing
      plasma cells in a patient with chronic antibiotic-refractory pouchitis (CARP).
      The role of serum IgG4 in the pathogenesis and clinical course of ileal pouch
      disorders has not been investigated. We hypothesized that IgG4-mediated
      autoimmunity may be a contributing factor in for CARP. The aims of the study were
      to investigate the prevalence of elevated serum IgG4 in symptomatic patients with
      ileal pouches and to characterize clinical features of pouch disorders in these
      patients. METHODS: A total of 124 consecutive symptomatic patients with ileal
      pouches from our subspecialty Pouchitis Clinic were enrolled in the study from
      January to October 2010. Serum IgG4 was measured at the time of presentation.
      Demographic, clinical, and laboratory characteristics were compared between the
      study (with serum IgG4 >=112 mg/dl) and control (with serum IgG4 <112 mg/dl)
      groups. RESULTS: There were ten patients (8.0%) with high serum IgG4 in the study
      group, while the remaining 114 (92%) patients were in the control group. The
      prevalence of elevated serum IgG4 in this series was 8%. None of the patients had
      a confirmed diagnosis of autoimmune pancreatitis. The median serum IgG4 in the
      study group was 144.5 vs. 14 mg/dl in the control group. The mean age of patients
      in the study and control groups was 35.5 +/- 14.5 and 42.0 +/- 13.2 years,
      respectively (p = 0.137). Two patients in the study group (20.0%) had concurrent
      autoimmune disorders as compared to 19 patients (16.7%) in the control group (p =
      0.788). Three (30.0%) patients in the study group had coexisting primary
      sclerosing cholangitis (PSC) in contrast to 15 (13.2%) in the control group (p =
      0.147). Among the study group patients, five (50.0%) had CARP and one (10%) had
      Crohn's disease (CD) of the pouch, while in the control group, 23 (20.2%) had
      CARP and 24 (21.1%) patients had CD of the pouch (p = 0.273). CARP was more
      commonly seen in patients with high serum IgG4 than patients with a normal IgG4
      (50.0% vs. 20.2%, p = 0.03). CONCLUSIONS: Approximately 8% of pouch patients
      presenting with symptoms of pouch dysfunction to our clinic had elevated serum
      IgG4. Patients with elevated serum IgG4 were more likely to have CARP.

PMID- 21725839
TI  - Prevention strategies for type 2 diabetes should be based on evidence-based
      medical nutrition data. Reply to Uusitupa M, Lindstrom J, Tuomilehto J [letter].

PMID- 21725840
TI  - EnRAGEd about death in type 1 diabetes.

PMID- 21725841
TI  - Is transferring an educational innovation actually a process of transformation?
AB  - Recent debates question the extent to which adopting an educational innovation
      requires compromise between the innovation's original design and the adoption
      site's context. Through compromises, the innovation's fundamental principles may
      be transferred, transformed, or abandoned. This paper analyzes such compromises
      during the piloting of Team-Based Learning (TBL). We ask: When is the process of
      transferring an innovation actually a process of transformation? This study is an
      autoethnography of our research team's implementation process. Autoethnographies
      are personalized accounts where authors draw on their own experiences to extend
      understanding of a particular topic. To conduct this autoethnography, we used an
      in-depth, interactive interview with the piloting clinician educator. In the
      analysis of TBL's fundamental principles, some aspects of the principles
      transferred easily, while others were transformed. Analysis raised concerns that
      the transformations threatened the foundational principles of TBL. While an
      educational innovation's techniques may seem to be surface structures, they are
      realizations of deeper fundamental principles. The fundamental principles are
      themselves realizations of the innovation's foundational philosophy. When
      techniques and/or principles are modified to a context, it is important to
      analyze if the modifications continue to uphold the innovation's philosophy.

PMID- 21725842
TI  - Study of hepatotoxicity and oxidative stress in male Swiss-Webster mice exposed
      to functionalized multi-walled carbon nanotubes.
AB  - Carbon nanotubes (CNTs), the most promising material with unique characteristics,
      find its application in different fields ranging from composite materials to
      medicine and from electronics to energy storage. However, little is known about
      the mechanisms behind the interaction of these particles with cells and their
      toxicity. The aim of this study was to assess the effects, after intraperitoneal
      (ip) injection, of functionalized multi-walled carbon nanotubes (MWCNT) (carboxyl
      groups) on various hepatotoxicity and oxidative stress biomarkers (ROS, LHP, ALT,
      AST, ALP, and morphology of liver) in the mouse model. The mice were dosed ip at
      0.25, 0.5, and 0.75 mg/kg/day for 5 days of purified/functionalized MWCNTs and
      two controls (negative; saline and positive; carbon black 0.75 mg/kg) as
      appropriate. Samples were collected 24 h after the fifth day treatment following
      standard protocols. Exposure to carboxylated functionalized MWCNT; the body
      weight gain of the mice decreased, induced reactive oxygen species (ROS), and
      enhanced the activities of serum amino-transferases (ALT/AST), alkaline
      phosphatases (ALP), and concentration of lipid hydro peroxide compared to
      control. Histopathology of exposed liver showed a statistically significant
      effect in the morphological alterations of the tissue compared to controls. The
      cellular findings reported here do suggest that purified carboxylated
      functionalized MWCNT has the potential to induce hepatotoxicity in Swiss-Webster
      mice through activation of the mechanisms of oxidative stress, which warrant in
      vivo animal exposure studies. However, more studies of functionalization in the
      in vivo toxicity of MWCNTs are required and parallel comparison is preferred.

PMID- 21725843
TI  - Unravelling the antimetastatic potential of pentoxifylline, a methylxanthine
      derivative in human MDA-MB-231 breast cancer cells.
AB  - Pentoxifylline (PTX), a methylxanthine derivative is a non-steroidal
      immunomodulating agent with unique hemorheologic properties. It is used in the
      treatment of intermittent claudication as it increases the amount of oxygen
      reaching tissues by increasing the flexibility of red blood cells. Recently, it
      has also shown to exhibit anti-metastatic and anti-angiogenic activities in
      B16F10 melanoma cells both in vitro as well as in vivo. As per the reports, the
      choice of drug in the treatment of breast cancer is paclitaxel, but the major
      limitation is its toxicity. However, the effects of PTX on metastatic processes
      in breast cancer are not currently known. Therefore, in this study, we have
      examined the effect of PTX in MDA-MB-231 human breast cancer cells. The MTT assay
      showed dose- and time-dependent decreases in cellular proliferation. The non
      toxic concentration of PTX selected were 1, 2.5 and 5 mM for 24 h. PTX induced a
      G0-G1 cell-cycle arrest leading to apoptosis. Further, it affected adhesion to
      both the matrigel and collagen type-IV in a time- and dose-dependent manner. The
      PTX impeded the migration of MDA-MB-231 cells and also decreased the activities
      of both MMP-2 and MMP-9. Thus, PTX at non-toxic doses affected cellular
      proliferation, adhesion, migration and invasion. These results demonstrate its
      anti-metastatic effect on MDA-MB-231 cells, and further studies need to be
      carried out to understand the mechanism of action.

PMID- 21725844
TI  - Preservative-free tafluprost 0.0015% in the treatment of patients with glaucoma
      and ocular hypertension.
AB  - INTRODUCTION: The objective of this study was to evaluate efficacy, local
      tolerability, and safety of this first-in-class preservative-free prostaglandin
      preparation in patients with ocular hypertension and glaucoma. METHODS: Patients
      with glaucoma or ocular hypertension who required a change of medication or were
      naive to treatment were included in this noninterventional and observational
      study. Noninterventional means that no influence was made upon the decision of
      the physicians to include specific patients and upon the treatment algorithm
      used. German law for observational studies does not allow any influence on the
      choice of drugs used, patient selection, masking, and comparator treatment
      regimens. The main aim of this observational study was to collect "real-life
      data" on the efficacy and safety of a new medical treatment after approval in a
      large patient population. Participating ophthalmologists were asked to provide
      anonymous patient data collected during regular visits by filling a simple data
      entry form. Intraocular pressure (IOP) readings were recorded at baseline
      (previous therapy or untreated) and 6-12 weeks after changing medical treatment
      to or initiating treatment with preservative-free tafluprost once daily. Changes
      in the IOP were evaluated over the study period for all patients as well as for
      specific pretreatment subgroups. Local comfort was determined using a five-point
      scale (very good, good, satisfactory, less satisfactory, not acceptable) before
      and after the change of medical treatment. All adverse events were recorded.
      RESULTS: Data from 2123 patients with glaucoma or ocular hypertension were
      considered for the final evaluation. Medication was changed in 41.1% of patients
      due to tolerability issues and in 25.6% of patients due to insufficient efficacy
      with prior medication. In all patients preservative-free tafluprost 0.0015%
      lowered IOP from 19.5 +/- 4.4 mmHg (baseline) to 16.4 +/- 2.9 mmHg after 6-12
      weeks. Preservativefree tafluprost also significantly lowered the IOP in all
      monotherapy subgroups: treatment-naive patients (n=440): 22.6 +/- 3.9 mmHg
      (baseline) to 16.7 +/- 2.7 mmHg (week 6-12); beta blockers (n=307): 20.3 +/- 3.5
      mmHg (baseline) to 16.7 +/- 2.6 mmHg (week 6-12); carbonic anhydrase inhibitors
      (n=158): 19.0 +/- 3.6 mmHg (baseline) to 16.0 +/- 2.6 mmHg (week 6-12);
      prostaglandin analogs (PGAs; n=447): 16.8 +/- 2.9 mmHg (baseline) to 15.8 +/- 2.6
      mmHg (week 6-12). Local comfort was rated as "very good" or "good" by 85.6% of
      patients at the final visit (P<0.001). Only few adverse events occurred during
      the treatment period: 18 patients (0.8%) discontinued medical treatment with
      preservative-free tafluprost due to local intolerance; six patients (0.3%) due to
      efficacy issues; four patients complained about systemic side effects (0.2%); and
      two patients preferred to use a multidose treatment regimen (0.2%). CONCLUSION:
      Although this study was limited by its observational design the results
      demonstrate that preservative-free tafluprost 0.0015% was effective, generally
      well tolerated, and safe in a broad and heterogeneous patient population.

PMID- 21725845
TI  - A comparative search for human FcepsilonRIalpha gene (FCER1A) 3'-UTR
      polymorphisms in Japanese and Polish populations.
AB  - The high affinity immunoglobulin E (IgE) receptor (FcepsilonRI) plays a key role
      in the pathogenesis of atopy and allergic disorders. Several polymorphisms
      located in 5'-flanking region and 5'-untranslated region (5'-UTR) of human
      FCER1A, the gene encoding FcepsilonRI alpha-subunit, have been shown to
      functionally affect its transcriptional activity. All those genetic variants have
      been also associated with allergic diseases and/or serum IgE levels. In the
      present study, we sought to identify functional polymorphisms in human FCER1A 3'
      untranslated region (3'-UTR), the potential candidates for future genetic
      association studies. Search for polymorphisms within human FCER1A 3'-UTR region,
      conducted in Japanese and Poles, revealed the presence of +5650A>G and +5714G>A
      variants. Subsequently, structure/distribution of haplotypes and LD measures were
      analyzed in Japanese and Poles for both 3'-UTR variants and the functional
      polymorphisms located in 5'-flanking region and 5'-UTR of human FCER1A.
      Additionally, reporter plasmids containing human FCER1A main promoter and 3'-UTR
      with all four possible combinations of +5650A>G and +5714G>A polymorphisms were
      constructed to evaluate functional potential of both 3'-UTR variants. However, no
      genotype-related differences in the gene expression were observed, as measured by
      reporter activity in cultured human basophil/mast cell-like KU812 cells,
      suggesting that both +5650A>G and +5714G>A have no genotype-related functional
      effect. In summary, we described linkage disequilibrium and the distribution of
      haplotypes for two identified human FCER1A 3'-UTR polymorphisms and several
      previously reported 5'-flanking region and 5'-UTR variants in Japanese and Poles,
      representative for East Asians and Caucasians, the two ethnic groups in which
      genetic associations between FCER1A and allergic diseases and/or serum IgE levels
      have been previously reported.

PMID- 21725846
TI  - Polymorphism of 5' regulatory region of ovine FSHR gene and its association with
      litter size in Small Tail Han sheep.
AB  - Single nucleotide polymorphisms of 5' regulatory region of follicle-stimulating
      hormone receptor (FSHR) gene were detected in two high prolificacy sheep breeds
      (Small Tail Han and Hu sheep) and two low prolificacy sheep breeds (Corriedale
      and Chinese Merino sheep) by polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP). The results indicated that there were three genotypes
      (AA, AB and BB) detected by primer 1 in Hu sheep while only one genotype (AA) in
      other three sheep breeds, and frequencies of AA, AB and BB genotypes in Hu sheep
      were 0.700, 0.225 and 0.075, respectively. There were three genotypes (EE, EF and
      EG) detected by primer 3 in Small Tail Han sheep while only EE genotype occurred
      in other three sheep breeds, and frequencies of EE, EF and EG genotypes in Small
      Tail Han sheep were 0.775, 0.200 and 0.025, respectively. No polymorphism was
      detected in four sheep breeds by primer 2 and primer 4. The sequencing results
      showed that there were two nucleotide mutations (g. -681T>C and g. -629C>T) in
      genotype BB compared with AA for primer 1. As for primer 3, two mutations (g. 
      197G>A and g. -98T>C) in genotype EF compared with EE and two mutations (g. 
      200G>A and g. -197G>A) in genotype EG compared with EE. The heterozygous ewes
      with EG or EF had 0.89 (P < 0.05) or 0.42 (P < 0.05) lambs more than homozygous
      ewes (EE genotype) in Small Tail Han sheep, respectively, while there was no
      significant difference on litter size between EG and EF ewes.

PMID- 21725847
TI  - Induction of toll-like receptor 2 positive antigen-presenting cells in spleen of
      pristane-induced arthritis in rats.
AB  - Toll-like receptors (TLRs) have been found to contribute to the pathogenesis of
      rheumatoid arthritis (RA). The aim of this study is to investigate the regulation
      and potential role of TLR2 in spleen of pristane-induced arthritis (PIA) rat,
      which can be used to further understand the mechanisms of RA. Arthritis in DA
      rats was induced by pristane. TLR2 expression in spleen was detected by real-time
      quantitative PCR and western blotting, and TLR2 expression at both mRNA and
      protein levels was upregulated in PIA rats. Peptidoglycan (PGN) was systemically
      administrated to PIA rats, and arthritis severity was evaluated macroscopically
      and microscopically. Results showed that systemic administration of PGN to PIA
      rats obviously deteriorated arthritis severity. TLR2 expression on splenocytes
      and different types of immune cells was measured by flow cytometry. And it was
      found that TLR2 was mainly expressed on antigen-presenting cells (APCs) of
      spleen, and the proportion of TLR2(+) dendritic cells and macrophages in spleen
      of PIA rats was increased remarkably. Thus, we conclude that the induction of
      TLR2(+) APCs in spleen may participate in the maintenance of PIA.

PMID- 21725848
TI  - Isolation and analysis of differentially expressed genes during asexual
      sporulation in liquid static culture of Ganoderma lucidum by suppression
      subtractive hybridization.
AB  - Ganoderma lucidum differentiates in liquid static culture by forming aerial
      mycelia and asexual spores, and this differentiation process is accompanied by
      higher production of anti-tumor compounds ganoderic acids. To gain an insight
      into the molecular events during asexual sporulation of G. lucidum, comparative
      transcriptome analysis using suppression subtractive hybridization (SSH)
      technique was performed to identify preferentially expressed genes in liquid
      static culture vs. in traditional shaking culture. After macroarray analysis of
      1920 cDNAs from SSH library, 147 unigenes which exhibited high expression in
      static culture were identified. Among these sequences, putative translations of
      88 unigenes possessed much similarity to known proteins involved in cell
      organization, signal transduction, cell metabolism, protein biosynthesis and
      transcription regulation; 13 had significant similarity to hypothetical proteins;
      the remaining 46 showed little or no similarity to GenBank sequences. RT-qPCR
      analysis confirmed increases in transcripts of selected genes under liquid static
      culture condition. The results of this study present the useful application of
      EST analysis on G. lucidum and provide preliminary indication of gene expression
      putatively involved in asexual sporulation process.

PMID- 21725849
TI  - Vasoactive intestinal peptide promotes gut barrier function against severe acute
      pancreatitis.
AB  - To explore the influence of vasoactive intestinal peptide (VIP) on the gut
      barrier function in severe acute pancreatitis (SAP). Fifty four SD rats were
      randomly divided into three groups: sham operated (SO) group, SAP group and VIP
      intervention group. Each group was further divided into three time points: 1, 6
      and 12 h after operation with 6 rats for each treatment point. SAP models were
      induced by retrograde injection of 4% sodium taurocholate into the bili
      pancreatic duct. VIP intervention group was made by 5 nmol VIP intraperitoneal
      injection within 5 min after SAP model successfully obtained. The VIP in plasma
      and intestinal homogenate were detected with ELISA. The endotoxin in plasma of
      all groups was also tested. The expression levels of TLR4, TNF-alpha, IL-6, and
      IL-10 in gut mucosa were measured by RT-PCR. Meanwhile intestinal samples were
      harvested for pathological examination. Compared to SO group, the VIP in plasma
      and intestinal homogenate of SAP group were significantly decreased at 1 h after
      induction, and then gradually increased to beyond the level of SO group at 12 h.
      The endotoxin of SAP group was continually increased. The mRNA levels of TLR4,
      TNF-alpha, IL-6, and IL-10 were also increased with obvious pathological injuries
      in the intestine. In the VIP group, endotoxin in plasma was obviously decreased
      compared to SAP group. The expressions of TNF-alpha, IL-6 mRNA were suppressed
      while IL-10mRNA was increased. The intestinal pathological injuries were also
      markedly alleviated. These results suggested that VIP had protective effects on
      SAP gut barrier function through inhibiting intestinal mucosal inflammatory
      responses.

PMID- 21725850
TI  - MDM2 SNP309 polymorphism and breast cancer risk: a meta-analysis.
AB  - The mouse double minute 2 (MDM2) gene encodes a phosphoprotein that interacts
      with P53 and negatively regulates its activity. SNP309 polymorphism (T-G) in the
      promoter of MDM2 gene has been reported to be associated with enhanced MDM2
      expression and tumor development. Many published studies have evaluated the
      association between MDM2 SNP309 polymorphism and breast cancer risk. However, the
      results were inconsistent. We combined and analyzed the data from 19 case-control
      studies including 14,450 cases and 13,382 controls. Crude odds ratios (ORs) with
      95% confidence intervals (CIs) were used to assess the strength of the
      association between MDM2 SNP309 polymorphism and breast cancer risk. No
      significant association was found in all genetic models in overall population.
      However, in subgroup analysis by ethnicity (4 studies in Asian group, 13 studies
      in European group, 2 studies of mixed population which were separated into 2
      European population group and 2 African population group), we found an increased
      breast cancer susceptibility for GT versus TT (OR = 1.31, 95% CI = 1.03-1.67) in
      Asian population and for GT versus TT (OR = 1.31, 95% CI = 1.03-1.66) in African
      population. When stratified by family history status (5 studies in familial
      breast cancer group, 5 studies in sporadic breast cancer group), homozygous
      subjects of sporadic breast cases carrying the T309G G allele exhibited elevated
      breast cancer risk (OR = 1.35, 95% CI = 1.00-1.82), whereas heterozygous carriers
      did not show significant association with breast cancer risk for GT vs. TT (OR =
      1.26, 95% CI = 0.84-1.87). Our meta-analysis suggests that MDM2 SNP309
      polymorphism may increase the risk to breast cancer in Asian and African
      population.

PMID- 21725851
TI  - Association between heme oxygenase-1 gene promoter polymorphisms and metabolic
      syndrome in Iranians.
AB  - Heme oxygenase-1 (HO-1) which is a rate-limiting enzyme in heme degradation
      processes shows a dinucleotide GT repeat in the promoter that alters the level of
      gene transcription. This study is aimed to assess the association of HO-1 gene
      promoter polymorphism and metabolic syndrome (MetS). A hundred and fifty two
      individuals, who were followed in Isfahan Cohort Study since 2001, were enrolled
      in this study. They consisted of 78 MetS patients and 74 controls without MetS.
      Blood samples were obtained from all participants and after extracting the
      genomic DNA, promoter sequence was determined by PCR-based genotyping. The serum
      levels of iron, ferritin and bilirubin were also measured in all subjects. The
      proportion of short and long allele frequency did not significantly differ in
      patients with metabolic syndrome compared to control group. In conclusion, the
      results showed that there is no significant difference between two groups in
      (GT)n repeat of HO-1 gene promoter. These findings suggest the insignificant role
      of genetic risk factors compared to environmental risk factors in the development
      of MetS.

PMID- 21725852
TI  - Metal ion and DNA binding by single-chain PvuII endonuclease: lessons from the
      linker.
AB  - Understanding the roles of metal ions in restriction enzymes has been complicated
      by both the presence of two metal ions in many active sites and their homodimeric
      structure. Using a single-chain form of the wild-type restriction enzyme PvuII
      (scWT) in which subunits are fused with a short polypeptide linker (Simoncsits et
      al. in J. Mol. Biol. 309:89-97, 2001), we have characterized metal ion and DNA
      binding behavior in one subunit and examined the effects of the linker on dimer
      behavior. scWT exhibits heteronuclear single quantum coherence NMR spectra
      similar to those of native wild-type PvuII (WT). For scWT, isothermal titration
      calorimetry data fit to two Ca(II) sites per subunit with low-millimolar K (d)s.
      The variant scWT|E68A, in which metal ion binding in one subunit is abolished by
      mutation, also binds two Ca(II) ions in the WT subunit with low-millimolar K
      (d)s. When there are no added metal ions, DNA binding affinity for scWT is
      tenfold stronger than that of the native WT, but tenfold weaker at saturating
      Ca(II) concentration. In the presence of Ca(II), scWT|E68A binds target DNA
      similarly to scWT, indicating that high-affinity substrate binding can be carried
      energetically by one metal-ion-binding subunit. Global analysis of DNA binding
      data for scWT|E68A suggests that the metal-ion-dependent behaviors observed for
      WT are reflective of independent subunit behavior. This characterization provides
      an understanding of subunit contributions in a homodimeric context.

PMID- 21725853
TI  - First step toward the "fingerprinting" of brain tumors based on synchrotron
      radiation X-ray fluorescence and multiple discriminant analysis.
AB  - Synchrotron-radiation-based X-ray fluorescence was applied to the elemental
      microimaging of neoplastic tissues in cases of various types of brain tumors. The
      following cases were studied: glioblastoma multiforme, gemistocytic astrocytoma,
      oligodendroglioma, anaplastic oligodendroglioma, ganglioglioma, fibrillary
      astrocytoma, and atypical transitional meningioma. Apart from neoplastic tissue,
      the analysis included areas of tissue apparently without malignant infiltration.
      The masses per unit area of P, S, Cl, K, Ca, Fe, Cu, Zn, Br, and Rb were used to
      construct a diagnostic classifier for brain tumors using multiple discriminant
      analysis. It was found that S, Cl, Cu, Fe, K, Br, and Zn are the most significant
      elements in the general discrimination of tumor type. The highest similarity in
      elemental composition was between atypical transitional meningioma and fibrillary
      astrocytoma. The smallest differentiation was between glioblastoma multiforme and
      oligodendroglioma. The mean percentage of correct classifications, estimated
      according to the a posteriori probabilities procedure, was 99.9%, whereas the
      mean prediction ability of 87.6% was achieved for ten new cases excluded
      previously from the model construction. The results showed that multiple
      discriminant analysis based on elemental composition of tissue may be a
      potentially valuable method assisting differentiation and/or classification of
      brain tumors.

PMID- 21725854
TI  - Intravenous administration of temozolomide as a useful alternative over oral
      treatment with temozolomide capsules in patients with gliomas.

PMID- 21725855
TI  - Elevated expression of macrophage migration inhibitory factor correlates with
      tumor recurrence and poor prognosis of patients with gliomas.
AB  - Macrophage migration inhibitory factor (MIF) plays a critical role in
      tumorigenesis. We aim to examine the association of MIF with tumor recurrence and
      survival of gliomas, and to determine whether MIF is a valuable prognostic
      predictor for glioma patients. The expression of MIF and interleukin 8 (IL-8) was
      evaluated in 36 high-grade gliomas (20 glioblastoma multiforme, 13 anaplastic
      astrocytoma, and 3 anaplastic oligoastrocytoma) and 32 low-grade gliomas (18
      fibrillary astrocytoma, 5 pilocytic astrocytoma, 5 oligodendroglioma, 3
      ependymoma and 1 pleomorphic xanthoastrocytoma) by immunostaining. Intratumoral
      microvessel density (IMD) of tumors in relation to immunostainings and
      clinicopathological factors were analyzed statistically as well as the follow-up
      data of patients. High expression of both MIF (58.8%) and IL-8 (52.9%) was
      significantly associated with high-grade gliomas and increased microvessels in
      tumors, but only high expression of MIF was closely related to tumor recurrence
      (P = 0.001). High expression of IL-8 exhibited a close correlation with high
      expression of MIF in tumors (P = 0.001). Histological grading, high expression of
      MIF and IL-8 correlated with patients' overall survival in univariate analysis.
      However, only histological grading and MIF expression exhibited a relationship
      with survival of patients as independent prognostic factors of glioma by
      multivariate analysis; the hazard ratios were 28.012 (P = 0.001) and 11.782 (P =
      0.001), respectively. Elevated production of MIF in glioma tumor cells may
      contribute to tumor recurrence and a worse prognosis. MIF may serve as an
      independent predictive factor for prognosis of glioma patients.

PMID- 21725856
TI  - Analysis of transcriptional and upstream regulatory sequence activity of two
      environmental stress-inducible genes, NBS-Str1 and BLEC-Str8, of rice.
AB  - Two abiotic stress-inducible upstream regulatory sequences (URSs) from rice have
      been identified and functionally characterized in rice. NBS-Str1 and BLEC-Str8
      genes have been identified, by analysing the transcriptome data of cold, salt and
      desiccation stress-treated 7-day-old rice (Oryza sativa L. var. IR64) seedling,
      to be preferentially responsive to desiccation and salt stress, respectively. NBS
      Str1 and BLEC-Str8 genes code for putative NBS (nucleotide binding site)-LRR
      (leucine rich repeat) and beta-lectin domain protein, respectively. NBS-Str1 URS
      is induced in root tissue, preferentially in vascular bundle, during 3 and 24 h
      of desiccation stress condition in transgenic 7-day-old rice seedling. In mature
      transgenic plants, this URS shows induction in root and shoot tissue under
      desiccation stress as well as under prolonged (1 and 2 day) salt stress. BLEC
      Str8 URS shows basal activity under un-stressed condition, however, it is
      inducible under salt stress condition in both root and leaf tissues in young
      seedling and mature plants. Activity of BLEC-Str8 URS has been found to be
      vascular tissue preferential, however, under salt stress condition its activity
      is also found in the mesophyll tissue. NBS-Str1 and BLEC-Str8 URSs are inducible
      by heavy metal, copper and manganese. Interestingly, both the URSs have been
      found to be non responsive to ABA treatment, implying them to be part of ABA
      independent abiotic stress response pathway. These URSs could prove useful for
      expressing a transgene in a stress responsive manner for development of stress
      tolerant transgenic systems.

PMID- 21725857
TI  - A ticking time bomb?: a case report of very late stent thrombosis more than 2
      years after fracture of a Cypher stent.

PMID- 21725858
TI  - Biomarkers of structural remodelling and endothelial dysfunction for prediction
      of cardiovascular events or death in patients with atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) is associated not only with inflammation
      but also with structural remodelling and altered endothelial activation which may
      contribute to clot formation, embolization and mortality. We aimed to determine
      the predictive value of single-time biomarker analysis for prediction of outcome
      in patients with AF. METHODS AND RESULTS: We conducted a prospective study to
      evaluate if biomarkers of structural, electrical or endothelial remodelling are
      predictive of cardiovascular events (composite primary endpoint of myocardial
      infarction, stroke, peripheral embolism or death). Secondary endpoint was all
      cause mortality. Patients with any type of AF and without active inflammatory
      conditions were eligible. Plasma samples were collected for ELISA analysis of
      biomarkers (inflammation [hsCRP, sCD40L], structural [MMP-2] and endothelial
      remodelling [vWF, sVCAM-1]) at enrolment. Patients (n = 278) were followed for 28
      +/- 12 (median 32) months. Eighty-eight individuals (32%) experienced a primary
      outcome event, including 8 (2.9%) with myocardial infarction, 13 (4.8%) with
      stroke and 4 (1.5%) with peripheral embolism. Predictors of the primary endpoint
      were age >75 years, CHADS(2)-score >2, LVEF <35%, diabetes, presence of an
      ICD/pacemaker, elevated vWF, sVCAM-1 and MMP-2 levels. On multivariate regression
      analysis, only age >75 years, sVCAM-1 and MMP-2 levels remained independently
      associated with the endpoint. There were 75 deaths during follow-up. Age >75
      years, reduced LVEF, elevated sVCAM-1 and MMP-2 levels were predictors of all
      cause mortality. CONCLUSION: In this cohort of AF patients, old age, elevated
      sVCAM-1 and MMP-2 levels were associated with cardiovascular events. Our data
      indicate that single-time biomarker assessment may be a useful tool to improve
      risk stratification schemes.

PMID- 21725859
TI  - Acute up-regulation of adipose triglyceride lipase and release of non-esterified
      fatty acids by dexamethasone in chicken adipose tissue.
AB  - The mechanism of adipose tissue lipolysis has not been fully elucidated. Greater
      understanding of this process could allow for increased feed efficiency and
      reduced fat in poultry. Studies in avian species may provide important insight in
      developing therapies for human obesity, as lipolytic pathways are highly
      conserved. Adipose triglyceride lipase (ATGL) cleaves triacylglycols, releasing
      non-esterified fatty acids (NEFA) into the bloodstream. Glucocorticoids have been
      shown to elevate circulating NEFA. To determine the regulation of ATGL and
      regulator proteins comparative gene identification-58 (CGI-58) and G(0)/G(1)
      switch gene 2 (G0S2) by glucocorticoid, 36 chickens received an injection of
      dexamethasone (4 mg/kg). Saline was administered to an additional 12 birds to
      determine any effect of stress during handling. Dexamethasone-injected birds were
      harvested at 0, 0.5, 1, 2, 4, and 6 h after treatment; saline-treated birds were
      collected at 4 and 6 h. Abdominal and subcutaneous adipose tissue and blood were
      collected. Gene and protein expression were analyzed via quantitative real-time
      PCR and western blot. Compared with the saline group, ATGL expression increased
      in birds injected with dexamethasone. When dexamethasone response was compared to
      the untreated group up to 6 h following injection, an increase in ATGL protein
      was observed as quickly as 0.5 h and increased further from 1 to 6 h. Plasma NEFA
      and glucose increased gradually from 0 to 6 h, reaching statistical significance
      at 4 h. These data show that ATGL expression is stimulated by glucocorticoid in a
      time-dependent manner.

PMID- 21725860
TI  - Association of life course socioeconomic disadvantage with future problem
      drinking and heavy drinking: gender differentials in the west of Scotland.
AB  - OBJECTIVE: To examine gender differentials in the association between life course
      socioeconomic disadvantage and the risk of exceeding internationally recognised
      weekly and daily guidelines for 'sensible' alcohol consumption and problem
      drinking. METHODS: A population-representative cohort study of 1,218 men and
      women from the west of Scotland, UK was conducted. Data on life course
      socioeconomic position were collected in 1987/1988 (at around 35 years of age).
      Alcohol consumption patterns (detailed 7-day recall) and problem drinking (CAGE
      questionnaire) were ascertained in 1990/1992. RESULTS: There was evidence of
      marked gender divergence in the socioeconomic position-alcohol intake/problem
      gradients. Typically, disadvantage in men conferred an increased risk of
      exceeding 'sensible' guidelines for weekly consumption (for own education and
      adult social class) and having alcohol problems (for employment status, income,
      adult social class and car ownership). In contrast, a reverse gradient was
      evident in women where adverse social status was generally associated with a
      reduced prevalence of these outcomes. CONCLUSION: Investigators should consider
      more carefully socioeconomic patterning of alcohol intake, and possibly other
      health-related behaviours, separately in men and women.

PMID- 21725861
TI  - Heterotrimeric Galpha subunit from wheat (Triticum aestivum), GA3, interacts with
      the calcium-binding protein, Clo3, and the phosphoinositide-specific
      phospholipase C, PI-PLC1.
AB  - The canonical Galpha subunit of the heterotrimeric G protein complex from wheat
      (Triticum aestivum), GA3, and the calcium-binding protein, Clo3, were revealed to
      interact both in vivo and in vitro and Clo3 was shown to enhance the GTPase
      activity of GA3. Clo3 is a member of the caleosin gene family in wheat with a
      single EF-hand domain and is induced during cold acclimation. Bimolecular
      Fluorescent Complementation (BiFC) was used to localize the interaction between
      Clo3 and GA3 to the plasma membrane (PM). Even though heterotrimeric G-protein
      signaling and Ca2+ signaling have both been shown to play a role in the response
      to environmental stresses in plants, little is known about the interaction
      between calcium-binding proteins and Galpha. The GAP activity of Clo3 towards GA3
      suggests it may play a role in the inactivation of GA3 as part of the stress
      response in plants. GA3 was also shown to interact with the phosphoinositide
      specific phospholipase C, PI-PLC1, not only in the PM but also in the endoplasmic
      reticulum (ER). Surprisingly, Clo3 was also shown to interact with PI-PLC1 in the
      PM and ER. In vitro analysis of the protein-protein interaction showed that the
      interaction of Clo3 with GA3 and PI-PLC1 is enhanced by high Ca2+ levels. Three
      way affinity characterizations with GA3, Clo3 and PI-PLC1 showed the interaction
      with Clo3 to be competitive, which suggests that Clo3 may play a role in the Ca2+
      triggered feedback regulation of both GA3 and PI-PLC1. This hypothesis was
      further supported by the demonstration that Clo3 has GAP activity with GA3.

PMID- 21725862
TI  - Ten-year natural course of habitual snoring and restless legs syndrome in a
      population aged 61-63 years at the baseline.
AB  - PURPOSE: We investigated the prevalence, natural course, and associated risk
      factors of habitual snoring (HS) and restless legs syndrome (RLS) over a period
      of 10 years among an aging population from their early sixties to their
      seventies. METHODS: A population-based follow-up study among all persons born in
      1935 and living in the city of Oulu in northern Finland was conducted. In this
      study, we examined subjects who had participated in two subsequent surveys
      conducted in 1996-1998 and 2007-2008. The data were gathered by questionnaires,
      as well as by laboratory and clinical measurements. RESULTS: Altogether 457 (55%)
      of the 838 eligible subjects participated in both surveys. The prevalence of both
      RLS and HS decreased during the 10 years from 21% to 15% and from 26% to 19%,
      respectively. Half of those who snored in 1996-1998 stopped snoring in 10 years
      time, and half of those who suffered from restless legs at least three times per
      week in 1996-1998 suffered from this syndrome never or less than once a week in
      2007-2008. The 10-year incidence of new cases of both HS and RLS was 7%. Male
      gender predicted best the incidence of new HS in 10 years, while the Zung sum
      score as a marker of depressive symptoms and waist circumference predicted RLS.
      CONCLUSIONS: Overall, the prevalence of both HS and RLS seems to diminish during
      aging. The causes behind this still remain unknown and should be investigated
      with more sophisticated methods.

PMID- 21725863
TI  - Isolation rates of Brucella melitensis in an endemic area and implications for
      laboratory safety.
AB  - A retrospective study was conducted to assess the potential threat posed by
      processing blood cultures to clinical microbiology laboratory personnel working
      in an area endemic for Brucella melitensis in southern Israel. The computerized
      laboratory records for the 2002-2009 period were reviewed, and the proportion of
      aerobic vials from which Brucella organisms were isolated out of the total number
      of positive aerobic blood culture vials was determined. During the 8-year period,
      B. melitensis was isolated in 514 of 20,620 (2.5%) positive vials. Isolation rate
      increased at the end of the period reaching a peak of 5.3% in 2008. Between April
      2008 and September 2009, the proportion of aerobic blood cultures from which B.
      melitensis was isolated was even higher than that positive for pneumococci (4.3%
      and 2.6%, respectively, P < 0.001). Although it has been recommended that
      processing of Brucella cultures should be confined to a Class II biologic safety
      cabinet, by the time the organism is identified, extensive manipulation of
      culture media has already been performed and inadvertent exposure of laboratory
      personnel may have already occurred. To reduce the risk of transmission, all
      positive blood culture vials in endemic areas should be processed in a safety
      cabinet.

PMID- 21725864
TI  - Development of a polymerase chain reaction (PCR) test for the detection of
      virulent forms of Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is a marine bacterium and some strains cause
      gastroenteritis in humans. Clinical isolates are thought to possess virulence
      factors that are absent from the majority of environmental isolates. Use of
      randomly amplified polymorphic DNA (RAPD)-PCR produced a unique 600 bp amplicon
      (band Y) in the majority of clinical isolates and rarely in environmental
      isolates tested. The DNA from band Y was cloned and sequenced and found to code
      for an outer membrane protein (OMP). Two polymerase chain reaction (PCR) primers
      were designed to specifically amplify a 200 bp unique sequence from presumptive
      virulent strains (PCR-OMP). The virulence of 23 clinical and 32 environmental
      isolates was assessed in cytotoxicity tests by treatment of Caco-2 cells with
      extracellular products (ECPs). All but two of the clinical isolates (91%) were
      positive for the 200 bp PCR-OMP and their ECPs produced a significantly higher (p
      < 0.05) lactate dehydrogenase (LDH) release (mean 72.88%) than the ECPs of
      environmental isolates (mean 15.3%) with the exception of one environmental
      isolate that produced the 200 bp amplicon. A positive 200 bp PCR-OMP is strongly
      correlated with virulence, as determined by the cytotoxicity assay, and
      identified virulent forms better than current PCR tests for tdh, trh or T3SS2.

PMID- 21725865
TI  - Etiology of acute gastroenteritis in children requiring hospitalization in the
      Netherlands.
AB  - Infectious gastroenteritis causes a considerable burden of disease worldwide.
      Costs due to gastroenteritis are dominated by the hospitalized cases. Effective
      control of gastroenteritis should be targeted at the diseases with the highest
      burden and costs. For that, an accurate understanding of the relative importance
      of the different bacterial, viral, and parasitic pathogens is needed. The
      objective of the present study was to determine the incidence and etiology of
      gastroenteritis requiring hospital admission in the Netherlands. Six hospitals
      enrolled patients admitted with gastroenteritis for approximately one year over
      the period May 2008 to November 2009. Participants provided questionnaires and a
      fecal sample, and the hospital filled out a clinical questionnaire. In total, 143
      children hospitalized for gastroenteritis and 64 matched controls were included
      in the study. Overall incidence of gastroenteritis requiring hospitalization was
      estimated at 2.92 per 1,000 children aged 0-17 years per year, with the highest
      incidence in children under the age of 5 years. The full diagnostic panel of
      pathogens could be studied in fecal samples of 96 cases. One or more pathogens
      were found in 98% of these cases. Co-infections were observed relatively often
      (40%). Viruses were detected in 82% of the samples, with rotavirus being most
      common (56%), bacteria in 32% and parasites in 10%. The present study emphasizes
      the importance of viral pathogens, especially rotavirus, in hospitalizations of
      children with gastroenteritis. Policies to reduce (costs of) hospitalizations due
      to gastroenteritis should therefore be first targeted at rotavirus.

PMID- 21725866
TI  - The options of C2 fixation for os odontoideum: a radiographic study for the C2
      pedicle and lamina anatomy.
AB  - INTRODUCTION: Patients with os odontoideum always present instability in
      atlantoaxial joint and need atlantoaxial fixation. C2 pedicle or laminar screws
      fixation has proven to be efficient and reliable for atlantoaxial instability.
      However, os odontoideum is a congenital or developmental disease, featured with
      anomalous bony anatomies. The anatomic measurements and guidelines for C2 pedicle
      screw placement in general population tends to differ with those of os
      odontoideum patients, for whom C2 pedicle screws are often needed. The option and
      techniques of C2 fixation are still challenging and yet to be fully explored.
      MATERIAL AND METHODS: We recruited 29 adult patients with os odontoideum and
      measured the dimension of C2 pedicle and lamina for each patient to examine how
      well do they match with the screws anatomically. In order to access the intra
      observer reliability and inter-observer repeatability of the measurements, the
      intraclass correlation coefficient (ICC) was also calculated. RESULTS: The
      results for reliability of the CT measurements showed excellent intraobserver
      (ICC = 0.95 and 0.96) and interobserver correlation coefficient (ICC = 0.93). The
      diameter and length of C2 pedicle were found to be 6.06 +/- 1.37 and 24.05 +/-
      2.54 mm, while the corresponding figures of C2 laminar were 6.95 +/- 0.82 and
      25.60 +/- 2.18 mm, respectively. In the measurements, all 29 cases had suitable
      diameter (larger than 5.5 mm) for C2 laminar screw (the laminar diameters ranged
      from 5.52 to 8.82 mm). In C2 pedicle measurements, the diameters of the 29 cases
      were from 3.50 to 9.86 mm, while 20 pedicles (34.5%) in 14 cases were less than
      5.5 mm in diameter. Six had bilateral small pedicles where the diameter was less
      than 5.5 mm. CONCLUSION: Anatomically, we found laminar screw is a better match
      in comparison with pedicle screw for C2 fixation in os odontoideum. The options
      for C2 fixation should be made based on careful preoperative imaging and thorough
      consideration. Preoperative reconstructive CT scan can offer great assistance for
      the choice of fixation in os odontoideum by revealing the anatomy of the C2
      pedicles in detail.

PMID- 21725867
TI  - Can quality or quality-of-life be defined?
AB  - The aim of this paper is to examine the oft-heard concern that quality or quality
      of-life cannot be defined. This concern persists today, even in the presence of
      countless studies that claim to be assessing quality or quality-of-life. There is
      obviously a disconnect here that warrants some attention, if not explanation. In
      this study, I summarize the extent of this disconnect and offer a number of
      potential explanations of why this situation exists. I review the role that
      operational definitions, statistical and empirical models, and content-specific
      definitions play in defining quality and/or quality-of-life. I conclude that none
      of these approaches provide a comprehensive definition of quality or quality-of
      life. In its stead, I will argue that quality or quality-of-life represents a
      distinctive pattern of thinking. I establish this pattern by examining the
      cognitive-linguistic basis of these definitions and argue that when this is done
      it will be possible to identify an universal cognitive (hybrid) construct that
      describes how a person thinks about all types of qualitative assessments. The
      implication of this is that for a study to claim that it is defining or assessing
      quality or quality-of-life, it will first have to demonstrate the presence of the
      elements of this hybrid construct.

PMID- 21725868
TI  - Decreased motility of human spermatozoa presenting phosphatidylserine membrane
      translocation-cells selection with the swim-up technique.
AB  - Phosphatidylserine membrane translocation (PST) is considered to be a marker of
      apoptosis; however, numerous studies have reported on its role in processes not
      related to cell death. The purpose of the study was to investigate: (1) what is
      the impact of PST on the motility of spermatozoa, and (2) does the swim-up
      isolation involve the percentage of cells presenting PST? Semen of 28
      normozoospermic men (WHO criteria) was analyzed. High motility spermatozoa were
      isolated by the swim-up technique. The percentage of spermatozoa with PST in neat
      semen and after swim-up isolation was assessed with Annexin-V labeled with
      fluorescein, using flow cytometry technique. The spermatozoas' motility was
      measured with a computer-assisted analysis system. The kinetic subpopulations of
      spermatozoa were identified with dedicated software and analyzed regarding PST.
      Vital spermatozoa with PST demonstrated progressive movement. The motion analysis
      system revealed a very strong positive correlation between the percentage of
      vital spermatozoa with PST and the percentage of spermatozoa belonging to the
      slow subpopulation (r = 0.83; p < 0.05), as well as a very strong negative
      correlation between the percentage of vital spermatozoa with PST and the
      percentage of spermatozoa belonging to the rapid subpopulation (r = -0.86; p <
      0.05). After the swim-up isolation, the percentage of vital spermatozoa
      presenting PST significantly decreased (2.4 +/- 2.1% vs. 5.2 +/- 2.4%; p < 0.05).
      Spermatozoa with PST present progressive movement; however, their motility is
      decreased. Isolation of spermatozoa with the swim-up technique eliminates the
      cells with PST.

PMID- 21725869
TI  - Prognostic factors of operated Rathke's cleft cysts with special reference to re
      accumulation and recommended surgical strategy.
AB  - BACKGROUND: Rathke's cleft cyst is known as an indolent disease, but has become
      intractable in a few cases. In this clinical investigation, the initial operative
      outcomes of Rathke's cleft cyst and the mechanism of re-accumulation were
      investigated to identify the optimum surgical strategy for the second operation.
      METHODS: We conducted a retrospective review of 155 patients with Rathke's cleft
      cyst (58 males and 97 females, aged from 13 to 84 years) surgically treated
      between April 1996 and March 2010. The same initial operative strategy was
      adopted in all patients. Operative outcomes and prognostic factors were
      investigated. FINDINGS: Re-accumulation occurred in 27 patients (17.4%), and re
      operation was required in eight patients because of neurological deficits (5.2%).
      Three types of re-accumulating mechanism were identified. First, cysts with
      cerebrospinal fluid (CSF)-like intensity on magnetic resonance imaging had a
      higher risk of re-accumulation (logrank test, p < 0.001). The cyst wall should be
      extensively removed in the suprasellar cistern to allow communication between the
      cyst and CSF spaces at the second operation. Second, cysts with epithelial
      transition had a significant higher risk of re-accumulation compared to other
      types of epithelium (logrank test, p < 0.001). Aggressive removal and irradiation
      should be performed at the second treatment. Third, classic Rathke's cleft cyst
      was found in the majority of cases. No change in operative strategy is required
      at the second treatment with lower risk of intractability. CONCLUSIONS:
      Enlargement of Rathke's cleft cyst requiring re-treatment needs selection of
      surgical strategy according to the individual re-accumulation mechanism.

PMID- 21725870
TI  - Identification and expression analysis of the zebrafish orthologue of Klotho.
AB  - Klotho is an aging suppressor gene. In mice, loss of Klotho function causes
      accelerated aging while increased Klotho expression increases longevity. This
      study aimed to identify and characterize the orthologue of Klotho in zebrafish, a
      powerful model organism for the investigation of development and human disease.
      Zebrafish klotho was identified by a bioinformatics approach, and cloning and
      sequencing of klotho cDNA confirmed the in silico analysis. The zebrafish Klotho
      protein has a structure similar to human and mouse Klotho, but it lacks an
      apparent secretory signal sequence. We can find no evidence of an alternative
      transcript isoform lacking the transmembrane domain coding sequence as seen in
      mammals. RT-PCR revealed the expression of klotho during embryonic development
      and in a wider variety of adult tissues than in mouse. Quantitative real-time RT
      PCR demonstrated the relative gene expression profile of zebrafish Klotho during
      embryogenesis and in adult tissues. In situ hybridization showed an apparently
      diffuse signal of klotho mRNA expression in the adult zebrafish testis.

PMID- 21725871
TI  - Facial convective heat exchange coefficients in cold and windy environments
      estimated from human experiments.
AB  - Facial heat exchange convection coefficients were estimated from experimental
      data in cold and windy ambient conditions applicable to wind chill calculations.
      Measured facial temperature datasets, that were made available to this study,
      originated from 3 separate studies involving 18 male and 6 female subjects. Most
      of these data were for a -10 degrees C ambient environment and wind speeds in the
      range of 0.2 to 6 m s(-1). Additional single experiments were for -5 degrees C, 0
      degrees C and 10 degrees C environments and wind speeds in the same range.
      Convection coefficients were estimated for all these conditions by means of a
      numerical facial heat exchange model, applying properties of biological tissues
      and a typical facial diameter of 0.18 m. Estimation was performed by adjusting
      the guessed convection coefficients in the computed facial temperatures, while
      comparing them to measured data, to obtain a satisfactory fit (r(2) > 0.98, in
      most cases). In one of the studies, heat flux meters were additionally used.
      Convection coefficients derived from these meters closely approached the
      estimated values for only the male subjects. They differed significantly, by
      about 50%, when compared to the estimated female subjects' data. Regression
      analysis was performed for just the -10 degrees C ambient temperature, and the
      range of experimental wind speeds, due to the limited availability of data for
      other ambient temperatures. The regressed equation was assumed in the form of the
      equation underlying the "new" wind chill chart. Regressed convection
      coefficients, which closely duplicated the measured data, were consistently
      higher than those calculated by this equation, except for one single case. The
      estimated and currently used convection coefficients are shown to diverge
      exponentially from each other, as wind speed increases. This finding casts
      considerable doubts on the validity of the convection coefficients that are used
      in the computation of the "new" wind chill chart and their applicability to
      humans in cold and windy environments.

PMID- 21725873
TI  - A randomized double-blind placebo-controlled study of Pu'er tea extract on the
      regulation of metabolic syndrome.
AB  - OBJECTIVE: To explore the regulative efficacy of Pu'er tea () extract on
      metabolic syndrome. METHODS: Ninety patients with metabolic syndrome were
      randomly divided into two groups, the intervention group administered with Pu'er
      tea extract, and the placebo group with placebo capsules. After 3 months'
      treatment, body mass index, waist hip ratio, blood lipids, blood sugar, immune
      and inflammatory index, and oxidation index of the patients with metabolic
      syndrome were tested and analyzed. RESULTS: In the intervention group, the body
      mass index, waist-hip ratio, fasting and 2 h postprandial blood glucose, serum
      total cholesterol, triglycerides, low density lipoprotein and apolipoprotein B
      100 all decreased in the patients with metabolic syndrome, and also the high
      density lipoprotein level increased and apolipoprotein A-1 showed the tendency to
      increase. Serum C-reactive protein, tumor necrosis factor-alpha, and interleukin
      6 were decreased in the intervention group. Interleukin-10 level was increased,
      MDA was decreased and superoxide dismutase was increased. Compared with before
      treatment and the placebo group, there were significant differences (P<0.05,
      P<0.01). CONCLUSIONS: Pu'er tea demonstrated excellent potential in improving
      central obesity, adjusting blood lipid, lowering blood sugar, regulating immunity
      and resisting oxidation. It can adjust the metabolic syndrome of different
      clinical phenotypes to different degrees, and is ideally fit for early prevention
      of metabolic syndrome.

PMID- 21725872
TI  - Effects and mechanisms of actions of Chinese herbal medicines for asthma.
AB  - Asthma is a chronic inflammatory disorder of airways that affects approximately
      300 million adults and children worldwide. Most therapy currently uses
      bronchodilators and corticosteroids. Systemic side effects from chronic use of
      these drugs are concern. Chinese medicine (CM) has a long history of human use in
      China and other Asian countries and well received by the patients. But as one
      component of Western integrative medicine (WIM), it is required that CM use is
      supported by scientific evidence. On the other hand, there are also suggestions
      that Western standardized medicine should consider personalized practice. In
      recent years there have been an increasing studies to narrow the gap between CM,
      the personalized medicine and Western medicine, evidence based medicine. This
      communication reviews several CM studies published in the English language in
      details by reviewing the effects and mechanisms of actions on asthma from clinic
      and experimental studies.Chinese herbal medicines exhibit broad actions on
      multiple asthma pathologic mechanisms. These mechanisms may involve
      antiinflammatory and immunomodulatory effects, inhibiting airway remodeling and
      normalization of hypothalamus, pituitary and adrenal (HPA)-axis disturbances.
      However, the mechanisms of actions of Chinese herbal medicines for asthma are not
      fully understood. More controlled clinical studies are warranted and some anti
      asthma CM may be proved to be effective when used as monotherapy or complementary
      asthma therapies.

PMID- 21725874
TI  - Synergistic effects of tetrandrine on the antifungal activity of topical
      ketoconazole cream in the treatment of dermatophytoses: a clinical trial.
AB  - OBJECTIVE: To evaluate the synergistic effects of tetrandrine (TET) on the
      antifungal activity of topical ketoconazole (KCZ) in the treatment of
      dermatophytoses. METHODS: The minimum inhibitory concentrations (MICs) for KCZ
      and combined KCZ and TET were compared in vitro. A randomized, double-blind trial
      was conducted among 97 patients with dermatophytoses who were assigned to 3
      groups and received: treatment with combination of 2% KZC and 2% TET cream (KCZ +
      TET group), or only 2% KZC cream (KCZ group), or 2% TET cream (TET group).
      Patients with tinea corporis and/or tinea cruris were treated for 2 weeks,
      separately. The patients with tinea pedis and/or tinea manuum were treated for 4
      weeks. RESULTS: Compared with KZC alone, combined use of KZC and TET showed lower
      MICs against clinical isolates of dermatophytes (P<0.05 for all). In the patients
      with tinea corporis and/or tinea cruris, the rates of overall cure (clinical cure
      plus mycologic clearance) were 81.25% vs. 33.33% for combined treatment and KZC
      monotherapy, respectively, after 4 weeks. All clinical indices were significantly
      different between the combination therapy and only KCZ therapy groups (P<0.05).
      Among the patients with tinea pedis and/or tinea manuum after 4 weeks treatment,
      the overall cure rates in the KCZ + TET group and KCZ group were 75.00% vs.
      40.00%, respectively. In the KCZ + TET group, all the clinical indices were
      significantly better than those in the KCZ group and TET group (P<0.05). The
      rates of overall efficacy in the TET group were all zero. No local skin redness
      or itching was observed during TET treatment. No clinically significant changes
      were found in post-treatment routine blood, urine, or stool tests, ECG, or tests
      for liver and kidney function; no serious adverse events occurred. CONCLUSION:
      TET synergistically enhanced the clinical efficacy of topical KZC cream in the
      treatment of dermatophytoses.

PMID- 21725875
TI  - Effect of electro-acupuncture on tumor necrosis factor-alpha and vascular
      endothelial growth factor in peripheral blood and joint synovia of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To observe the effect of electro-acupuncture (EA) on tumor necrosis
      factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in
      peripheral blood and joint synovia in patients with rheumatoid arthritis (RA) to
      verify the clinical efficacy of EA. METHODS: Adopting randomized controlled
      principle, the 63 RA patients enrolled were assigned to two groups, the 32
      patients in the EA group were treated with EA, and the 31 patients in the simple
      needling (SN) group treated with simple needling. According to the integral-local
      combining method, the acupoints were selected mainly from yang-meridian and local
      Ashi points (pain-point). EA or SN was applied every other day, 10 times as a
      course, and each patient received a total of 3 courses of treatment. RESULTS:
      Blood and synovial levels of TNF-alpha and VEGF were reduced significantly after
      treatment in both groups. The lowering (absolute value and difference value) of
      TNF-alpha as well as the absolute value of VEGF, either in blood or in synovia,
      were similar in the two groups (P>0.05); but the lowering of VEGF after treatment
      was more significant in the EA group than that in the SN group (P<0.05).
      CONCLUSION: EA could effectively lower the contents of TNF-alpha and VEGF in
      peripheral blood and joint synovia to improve the internal environment for
      genesis and development of RA, so as to enhance the clinical therapeutic
      effectiveness.

PMID- 21725876
TI  - Research on the relationship between thick greasy tongue fur formation and
      vascular endothelial cell permeability with the protein expression of zonula
      occludens-1.
AB  - OBJECTIVE: To determine the relationship of thick greasy tongue fur formation and
      permeability of vascular endothelial cells (ECs) with the protein expression of
      zonula occludens-1 (ZO-1). METHODS: Sprague Dawley rats were randomly divided
      into a model group of severe acute pancreatitis (SAP) and a sham-operated (SO)
      group. The SAP rats were further divided into two subgroups on the basis of
      tongue-coating status: a thick greasy tongue fur group (SAP-TGF) and a normal
      tongue fur group (SAP-NF). Six rats were chosen randomly from every group
      mentioned above for an Evans blue assay 5 days after model establishment. For the
      histomorphology analysis, the expressions of ZO-1 protein and mRNA were studied
      by hematoxylin-eosin (H&E) staining, transmission electron microscope, Western
      blot, and Q-PCR using blood and tongue tissues, which were collected from 8 rats
      randomly chosen from each group. RESULTS: The papillae density of the rat tongue
      surface and the caryocinesis frequency of the basal layer were significantly
      increased in the SAP-TGF group compared with the SO group (P<0.05). Evans blue
      levels in the tongue tissue of the SAP-TGF group were significantly higher than
      that of the SO and SAP-NF groups (P<0.05). Vascular ECs were wider and obviously
      fissured in the SAP-TGF group under transmission electron microscope observation.
      The protein and mRNA expression of ZO-1 in the SAP-TGF group were lower than
      those in the SAP-NF (P<0.05). CONCLUSIONS: Reproductive activity enhancement of
      glossal epithelial cells was one of the main characteristics of thick greasy
      tongue fur formation. An increase in vasopermeability was closely associated with
      thick greasy tongue fur formation. Tight junction structural variation of
      vascular ECs might play an important role in the pathological and physiological
      process of thick greasy tongue fur formation.

PMID- 21725878
TI  - Experimental study on the molecular mechanism of anthraquinone cathartics in
      inducing melanosis coli.
AB  - OBJECTIVE: To explore the significance of colonic epithelial cell apoptosis and
      tumor necrosis factor alpha (TNF-alpha) changing in pathogenesis of melanosis
      coli (MC) in guinea pig and the molecular mechanism of rhubarb (Rhu) in inducing
      the disease, by means of using different dosages of Rhu to induce the disease.
      METHODS: One hundred and forty-four male guinea pigs, clean grade, were
      randomized according to their body weight into 5 groups, the untreated normal
      group and the 4 Rhu groups treated, respectively, with different doses of Rhu, 3
      g/kg.d for low dose (Rhu-l) group, 6 g/kg.d for moderate dose (Rhu-m) group, 12
      g/kg.d for high dose (Rhu-h) group and 24 g/kg.d for super-high dose (Rhu-s)
      group via gastric infusion. All animals were sacrificed 60 days later, their
      viscera were taken for observing the pathologic and morphologic changes with HE,
      melanin and melatonin staining, and the apoptosis of colonic epithelial cells was
      detected with TUNEL stain and transmission electric microscopy. In addition, the
      levels of TNF-alpha in serum and colonic tissue were measured using ELISA and RT
      PCR. RESULTS: The pathological changes of MC could be found by naked eye in all
      Rhu groups, especially apparent at caecum and proximal end of colon, but did not
      found in gallbladder, jejunum and ileum. In normal guinea pigs, the colonic
      membrane was pink in color with no apparent pigment deposition. Membranous color
      deepened in the Rhu groups depending on the dosage of Rhu used. MC scoring showed
      the highest scores revealed in the Rhu-s group (6.00+/-0.00), which was
      significantly different to those in the Rhu-l (3.86+/-0.69), Rhu-m (4.43+/-0.79)
      and Rhu-h groups (4.88+/-0.35, all P<0.05). Levels of cell apoptosis in colon and
      TNF-alpha in serum in all Rhu groups were higher than those in the normal group
      (P<0.01), but showed no significant difference among the Rhu groups (P>0.05).
      Moreover, a positive correlation was found in the degree of induced MC with
      apoptosis rate and TNF-alpha level. CONCLUSIONS: Rhu (anthraquinone purgatives)
      had apparent effect on inducing MC; its molecular mechanism is maybe to destroy
      intestinal mucosal barrier and advance proinflammatory factor TNF-alpha
      releasing, which leads to colonic epithelial cells apoptosis, and finally induce
      the change of MC due to the deposition of brown pigments, i.e. the macrophage
      phagocytized apoptotic body, on the colonic membrane.

PMID- 21725877
TI  - In vitro antimetastatic effect of Changweiqing through antiinvasion of hypoxic
      colorectal carcinoma LoVo cells.
AB  - OBJECTIVE: To investigate the in vitro effects and the primary mechanisms of
      Changweiqing (, CWQ) on antimetastasis and antiinvasion of hypoxic colon
      carcinoma cells. In addition, to provide experimental evidence for the Chinese
      medicinal theory of "strengthening the body's resistance to eliminate pathogenic
      factors" in the treatment of colorectal cancer, including its invasion and
      metastasis. METHODS: First, CWQ sera were prepared with serum-pharmacology
      methods. Then, the modified hypoxic chamber was designed and flushed with 5%
      CO(2) and 95% N(2) at 37  degrees C to induce a hypoxic environment. The effect
      of CWQ serum on the viability of LoVo cells was tested with MTT cytotoxicity
      assay. The wound model and chamber model were established to estimate the effects
      of CWQ serum on migration and invasion of LoVo cells. The model for cell adhesion
      was established to evaluate the effect of CWQ serum on LoVo cells' adhesion. The
      gelatin zymography model was performed to determine the effects of CWQ serum on
      the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase
      9 (MMP-9). The effects of CWQ serum on the hypoxia-inducible factor 1 alpha (HIF
      1alpha) nuclear translocation and the mRNA level of vascular endothelial growth
      factor (VEGF) in LoVo cells were determined by Western blot and reverse
      transcription-polymerase chain reaction (RT-PCR) analyses, respectively. RESULTS:
      CWQ inhibited LoVo cells' migration based on wound healing assay. The inhibitive
      effect could reach about 68.00% under hypoxic culture and about 29.87% under
      normoxic culture when cells were treated with 10% CWQ serum for 24 h. The results
      from both cell invasion and adhesion assays showed that CWQ serum could dose
      dependently repress the invasion of LoVo cells and inhibit cells from adhering to
      extra cellular matrix (ECM). Under the hypoxic culture condition, RT-PCR analysis
      showed that 10% CWQ serum had down-regulated the expression of VEGF by 45.87%,
      and the result of Western blot analysis provided further evidence. The HIF-1alpha
      amount in the nucleus of the LoVo cells was also diminished in a dose-dependent
      manner, as shown by the Western blot. Gel zymogram assay revealed that CWQ serum
      could suppress the activities of MMP-2 and MMP-9. CONCLUSIONS: CWQ could
      effectively inhibit tumor metastasis in vitro The antimetastatic effects of CWQ
      were associated with the inhibition of cell motility, which was evidenced by
      inhibition of cell invasion and adhesion. The molecular mechanisms of the
      inhibition of tumor invasion by CWQ were due to the reduced expression of both
      HIF-1alpha and VEGF and the suppression of MMP-2 and MMP-9 expression.

PMID- 21725879
TI  - The regulatory effects of polyporus polysaccharide on the nuclear factor kappa B
      signal pathway of bladder cancer cells stimulated by Bacillus Calmette-Guerin.
AB  - OBJECTIVE: To detect the effects of Polyporus polysaccharide (PPS), Bacillus
      Calmette-Guerin (BCG), and their combination on the nuclear factor kappa B (NF
      kappaB) signaling pathway associated-gene expression and investigate the
      molecular mechanisms of the toxic-reducing effect of PPS in coordination with BCG
      against bladder cancer. METHODS: After T739 cells were treated with PPS, BCG and
      their combination, the changes in mRNA and protein expression of inhibitor of
      kappa B kinase beta (IKKbeta), NF-kappaB subunit p65 (NF-kappaB p65),
      intracellular adhesion molecule 1 (ICAM1) and chemokine (C-c motif) ligand 2
      (CCL2) in bladder cancer cell line T739 were determined by relative quantitative
      real-time PCR, Western blot, and flow cytometry (FCM). NF-kappaB p65 DNA-binding
      activity in T739 cell was detected by biotinylated probe-ELISA, and NF-kappaB p65
      nuclear expression in T739 cell was observed by immunohistochemistry. RESULTS:
      Compared with the T739 control group, the mRNA expression of IKBKB (IKKbeta), Rel
      A (NF-kappaB p65), ICAM1 and CCL2 in T739 cells treated with BCG were increased
      obviously (Ratio>2.0), as well as the expression of IKKbeta, CCL2 and ICAM1
      proteins. Meanwhile, NF-kappaB p65 DNA-binding activity and NF-kappaB p65 nuclear
      expression in T739 cells treated with BCG were up-regulated significantly
      (P<0.05). Compared with the control, the increased expression in T739 cells were
      simultaneously down-regulated after PPS treatment, except for ICAM1 protein
      expression. With cells treated with a combination of BCG and PPS, the expression
      of genes associated with the NF-kappaB signaling pathway, such as IKBKB, ICAM1
      and CCL2, were all down-regulated compared to the BCG group, as well as Rel A
      mRNA expression, NF-kappaB p65 DNA-binding activity and NF-kappaB p65 nuclear
      expression. CONCLUSIONS: PPS could inhibit the over-activation of the NF-kappaB
      signaling pathway induced by BCG in bladder cancer cells and accordingly
      attenuate the adverse reactions to BCG therapy.

PMID- 21725880
TI  - Effect of San'ao Decoction on the airway inflammation and hyperresponsiveness in
      a murine model of lipopolysaccharide-enhanced asthma.
AB  - OBJECTIVE: San'ao Decoction (, SAD), as a representative Chinese medicine (CM)
      formula, was chosen to evaluate the effect of airway inflammation and
      hyperresponsiveness on the lipopolysaccharide (LPS) enhanced asthma model.
      METHODS: The asthma model was reproduced in the Balb/C mice sensitized by
      ovalbumin (OVA), challenged by OVA and LPS. After Balb/C mice's administration of
      a dose (0.0024 g/kg) of dexamethasone acetate, and three doses (2.2 g/kg, 4.4
      g/kg and 8.8 g/kg) of SAD, airway inflammation and responsiveness were observed.
      The airway inflammation was detected by counting bronchoalveolar lavage fluid
      (BALF) cells and lung histopathology. Also, differential expressions of
      interferon-r (IFN-gamma), interleukin-4 (IL-4), and IL-5 in the supernatants of
      BALF were examined. The changes in airway responsiveness indicated by lung
      resistance (R(L)) and stimulated by acetylcholine (Ach) were determined. RESULTS:
      Small-dose SAD hardly inhibit airway inflammation or hyperresponsiveness in the
      LPS-enhanced asthma, while medium-dose and high-dose SAD significantly inhibited
      the airway hyperresponsiveness, and to some extent, reduced airway inflammation.
      Meanwhile, the small-dose, medium-dose, and high-dose SAD promoted Th1-type
      cytokines (IFN-gamma) and reduced Th2-type cytokines (IL-4, IL-5) to different
      extents, which led to a Th1/Th2 balance. CONCLUSION: SAD has a good therapeutic
      effect on airway hyperresponsiveness in the LPS-enhanced asthma model, but its
      definite influence on airway inflammation is not remarkable.

PMID- 21725881
TI  - Protective effects of the preconditioning with different doses of sodium
      aescinate on tourniquet-induced ischemic reperfusion.
AB  - OBJECTIVE: To evaluate the protective effects of sodium aescinate (SA)
      preconditioning on the tourniquet-induced ischemia-reperfusion (I/R) injury after
      limbs operation. METHODS: Seventy-five patients with grade I-II issued by
      American Society of Anesthesiology undergoing lower limb operation were randomly
      assigned to 3 groups: the control group, low-dose SA-treated group and high-dose
      SA-treated group; each group enrolled 25 patients. The patients were treated with
      5 mg and 10 mg SA 30 min before tourniquet inflation in the two treatment groups
      separately, while the patients in the control group received normal saline.
      Venous blood samples were obtained before tourniquet was inflated (T0 baseline).
      And 5 (T1), 10 (T2), 20 (T3) min after tourniquet was released. The nitric oxide
      (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined
      by commercial kits. Meanwhile, arterial pressure (MAP) and heart rate (HR) were
      monitored from an automatic invigilator. RESULTS: In the control group, MDA and
      NO levels were increased, and SOD and MAP were decreased significantly after
      tourniquet deflation compared to T0 baseline (P<0.05). After tourniquet
      deflation, MDA and NO levels in the two treated groups were significantly
      decreased; meanwhile, SOD levels and MAP were increased, and the variations of HR
      were more stable compared with the control group (all P<0.05). There was no
      significant difference in all of the above between the two treated groups
      (P>0.05). CONCLUSION: The protective effects of SA preconditioning on tourniquet
      induced limb I/R injury might possibly contribute to the increasing of SOD
      levels, and MAP and the decreasing of MDA and NO levels.

PMID- 21725882
TI  - Assessing the success of masking in acupuncture trials: further insight.

PMID- 21725884
TI  - Interventional value of total flavonoids from Rhizoma Drynariae on Cathepsin K, a
      potential target of osteoporosis.
AB  - Osteoporosis, the sixth most common disease in the world, is bringing
      increasingly serious harm to people's health. Cathepsin K, which plays an
      important role in bone resorption, is a potential target in the treatment of
      osteoporosis. Total flavonoids, the active ingredients in Rhizoma Drynariae, have
      shown obvious, therapeutic effect on osteoporosis. In previous studies, it was
      presumed that the mechanism for the therapeutic effect was through inhibiting the
      expression of Cathepsin K. However, there are still no detailed reports on some
      key issues such as the specific inhibitory results of total flavonoids on
      Cathepsin K and the pathway of inhibition and so on. Based on previous studies on
      total flavonoids from Rhizoma Drynariae, the pathway for the effect of, total
      flavonoids inhibiting Cathepsin K and their interventional value on Cathepsin K
      were analyzed in this paper, so as to explore the interventional feasibility and
      value of total flavonoids in Rhizoma Drynariae on Cathepsin K.

PMID- 21725883
TI  - Chinese medicine and the surgeon.
AB  - The surgeon aims at a direct, complete removal of the pathology. In spite of the
      modern advancements of imaging facilities and precision instrumentations,
      unsatisfactory results and recurrences are not uncommon. This paper provides a
      general review of the four specific areas in surgery that would benefit from
      Chinese medicine. Extensive searches were made on four surgical areas based on
      available English language journals, viz. low-back pain, chronic ulcers, renal
      calculus, and enuresis in children, in the past 10 years. The quoted
      communications are mainly related to clinical evidences, while a smaller number
      of crucial laboratory reports are also included. Low-back pain, a most frequent
      orthopaedic problem, would benefit from acupuncture treatment. Chronic leg ulcers
      could achieve better results of healing using herbal supplements. Problems of
      renal stones, besides the conventional methods of removal, could be further
      supplemented with herbal drinks that aim at prevention of recurrences. Enuresis
      in children, an untreatable common condition, may respond well to acupuncture.
      Surgeons should keep an open mind. In case of difficulties, they could seriously
      consider options of traditional treatment.

PMID- 21725885
TI  - Important role of hydrophobic interactions in high-pressure adaptation of
      proteins.

PMID- 21725886
TI  - Identification of genes influencing synthetic lethality of genetic and epigenetic
      alterations in translation termination factors in yeast.

PMID- 21725887
TI  - Recognition of lipid-protein rafts in vacuolar membrane.

PMID- 21725888
TI  - FUS gene mutations associated with familiar forms of amyotrophic lateral
      sclerosis affect cellular localization and aggregation properties of the encoded
      protein.

PMID- 21725889
TI  - The formation of metastable bond between protons and mitoplast surface.

PMID- 21725890
TI  - Tris-2(hydroxyethyl)ammonium 2-methylphenoxyacetate activates the synthesis of
      mRNA aminoacyl-tRNA synthetase.

PMID- 21725891
TI  - Adaptation of mycoplasmas to environmental conditions: features of the proteome
      shift in Acholeplasma laidlawii PG8 at persistent exposure to stressors.

PMID- 21725892
TI  - The luminescent system of the luminous fungus Neonothopanus nambi.

PMID- 21725893
TI  - Quantitative estimation of dragonfly role in transfer of essential
      polyunsaturated fatty acids from aquatic to terrestrial ecosystems.

PMID- 21725894
TI  - Effect of redox conditions on the synthesis and phosphorylation of beta-subunit
      of mitochondrial F(0)F (1)-ATPase of maize (Zea mays).

PMID- 21725895
TI  - Genes potentially associated with cisplatin resistance of lung cancer cells.

PMID- 21725896
TI  - Role of ADARs in mouse development.
AB  - RNA editing by deamination of adenosine to inosine (A-to-I editing) is a
      physiologically important posttranscriptional mechanism that can regulate
      expression of genes by modifying their transcripts. A-to-I editing is mediated by
      adenosine deaminases acting on RNA (ADAR) that can catalytically exchange
      adenosines to inosines, with varying efficiency, depending on the structure of
      the RNA substrates. Significant progress in understanding the biological function
      of mammalian ADARs has been made in the past decade by the creation and analysis
      of gene-targeted mice with disrupted or modified ADAR alleles. These studies have
      revealed important roles of ADARs in neuronal and hematopoietic tissue during
      embryonic and postnatal stages of mouse development.

PMID- 21725897
TI  - Nuclear Editing of mRNA 3'-UTRs.
AB  - Hundreds of human genes express mRNAs that contain inverted repeat sequences
      within their 3'-UTRs. When expressed, these sequences can be promiscuously edited
      by ADAR enzymes, leading to the retention of mRNAs in nuclear paraspeckles. Here
      we discuss how this retention system can be used to regulate gene expression.

PMID- 21725898
TI  - Intralymphatic immunotherapy: from the rationale to human applications.
AB  - Allergen specific immunotherapy (SIT) is the only treatment of IgE mediated
      allergies that is causative and has a long-term effect. Classically, SIT requires
      numerous subcutaneous injections of the allergen during 3-5 years. Over the last
      decade sublingual allergen applications have established as an alternative, but
      treatment duration could not be shortened. This review focuses on direct
      administration of vaccines in general and of allergens in particular into lymph
      nodes with the aim to enhance immunotherapy. Several studies have found that
      direct injection of antigens into lymph nodes enhanced immune responses. Recently
      we have focused on intralymphatic allergen administration in order to enhance
      SIT. Data in mouse models and in clinical trials showed that intralymphatic
      allergen administration strongly enhanced SIT, so that the number of allergen
      injections could be reduced to three, and the allergen dose could be reduced 10
      100 fold. Intralymphatic injections proved easy, practically painless and safe.
      In mice and men, intralymphatic immunotherapy injecting allergens into a
      subcutaneous lymph node markedly enhances the protective immune response, so that
      both the dose and number of allergen injections can be reduced, making SIT safer
      and faster, which enhances patient convenience and compliance.

PMID- 21725899
TI  - Clinical and biological significance of never in mitosis gene A-related kinase 6
      (NEK6) expression in hepatic cell cancer.
AB  - Nek6 is a cell cycle regulatory gene, which can control cell proliferation and
      survival. Recent studies suggested that desregulation of Nek6 expression plays a
      key role in oncogenesis. This study was aimed to investigate the potential roles
      of Nek6 in hepatocellular carcinoma (HCC) development. Immunohistochemistry and
      Western blot analysis was performed for Nek6 in 80 hepatocellular carcinoma
      samples. The data were correlated with clinicopathological features. The
      univariate and multivariate survival analyses were performed to determine the
      prognostic significance of Nek6 in HCC. In addition, Nek6 expression vector was
      used to detect its role in cell cycle control. Nek6 was overexpressed in
      hepatocellular carcinoma as compared with the adjacent normal tissue. High
      expression of Nek6 was associated with histological grade and the level of alpha
      fetal protein, and Nek6 was positively correlated with proliferation marker Ki
      67. Univariate analysis showed that Nek6 expression was associated with poor
      prognosis. Multivariate analysis indicated that Nek6 and Ki-67 protein expression
      was an independent prognostic marker for HCC. While in vitro, following release
      from serum starvation of HuH7 HCC cell, the expression of Nek6 was upregulated.
      Overexpression Nek6 in Huh7 cell could promote the cell cycle. In conclusion,
      Nek6 is involved in the pathogenesis of hepatocellular carcinoma. It may be a
      favorable independent poor prognostic parameter for hepatocellular carcinoma.

PMID- 21725900
TI  - Exercise therapy for fibromyalgia.
AB  - Fibromyalgia syndrome, a chronic condition typically characterized by widespread
      pain, nonrestorative sleep, fatigue, cognitive dysfunction, and other somatic
      symptoms, negatively impacts physical and emotional function and reduces quality
      of life. Exercise is commonly recommended in the management of people with
      fibromyalgia, and interest in examining exercise benefits for those with the
      syndrome has grown substantially over the past 25 years. Research supports
      aerobic and strength training to improve physical fitness and function, reduce
      fibromyalgia symptoms, and improve quality of life. However, other forms of
      exercise (e.g., tai chi, yoga, Nordic walking, vibration techniques) and
      lifestyle physical activity also have been investigated to determine their
      effects. This paper highlights findings from recent randomized controlled trials
      and reviews of exercise for people with fibromyalgia, and includes information
      regarding factors that influence response and adherence to exercise to assist
      clinicians with exercise and physical activity prescription decision-making to
      optimize health and well-being.

PMID- 21725901
TI  - Role of cerebrospinal fluid and plasma biomarkers in the diagnosis of
      neurodegenerative disorders and mild cognitive impairment.
AB  - Biomarkers are one type of laboratory testing being developed in response to the
      therapeutic imperative for diseases that cause cognitive impairment and dementia.
      The role of biomarkers is already transforming the organization and conduct of
      clinical trials, and if successful will likely contribute in the future to the
      medical management of patients with these diseases. Despite the obvious utility
      of practicality of blood- or urine-based biomarkers, so far results from these
      fluid compartments have not been reproducible. In contrast, substantial progress
      has been made in cerebrospinal fluid biomarkers. Here we review the stages of
      cerebrospinal fluid biomarker development for several common and unusual diseases
      that cause cognitive impairment and dementia, stressing the distinction between
      diagnostic and mechanistic biomarkers. Future applications will likely focus on
      diagnosis of latent or early-stage disease, assessment of disease progression,
      mechanism of injury, and response to experimental therapeutics.

PMID- 21725902
TI  - Upfront therapy of acute myeloid leukemia.
AB  - Acute myeloid leukemia is a clinically and biologically heterogeneous disease.
      Standard induction chemotherapy, consisting of cytarabine and an anthracycline,
      has not changed substantially over several decades, and outcomes remain
      suboptimal, particularly in older patients. Many genetic and molecular changes
      have been identified that guide selection of post-remission therapy and for which
      targeted therapies are beginning to be developed and tested. These research
      efforts are resulting in gradual improvement in outcomes. We will review here
      recent advances in induction chemotherapy, including anthracycline dose
      intensification in younger patients, treatment selection and use of novel agents
      in upfront therapy for older patients, and risk-adapted post-remission therapy.

PMID- 21725903
TI  - Ectopic expression of blood type antigens in inflamed mucosa with higher
      incidence of FUT2 secretor status in colonic Crohn's disease.
AB  - BACKGROUND: Host-intestinal microbial interaction plays an important role in the
      pathogenesis of inflammatory bowel diseases (IBDs). The surface molecules of the
      intestinal epithelium act as receptors for bacterial adhesion and regulate the
      intestinal bacteria. Some known receptors are the mucosal blood type antigens,
      which are regulated by the fucosyltransferase2 (FUT2) gene, and individuals who
      express these antigens in the gastrointestinal tract are called secretors. Recent
      research has revealed that the FUT2 gene is associated with Crohn's disease (CD)
      in western populations. METHODS: To clarify the contribution of mucosal blood
      type antigens in IBD, we determined the incidence of five previously reported
      single-nucleotide polymorphisms of the FUT2 gene in Japanese patients. We also
      used immunohistochemistry to investigate the antigen expression in mucosal
      specimens from IBD patients and animal models. RESULTS: Genetic analysis revealed
      that all of the patients with colonic CD were secretors, whereas the incidence of
      secretors was 80, 80, 67, and 80%, respectively, for the control, ileocolonic CD,
      ileal CD, and ulcerative colitis groups (P = 0.036). Abnormal expression of blood
      type antigens was observed only in colonic CD. Interleukin-10-/- mice, but not
      dextran sulfate sodium colitis mice, had enhanced colonic expression of blood
      type antigens, and the expression of these antigens preceded the development of
      colitis in the interleukin-10-/- mice. CONCLUSIONS: FUT2 secretor status was
      associated with colonic-type CD. This finding, taken together with the
      immunohistochemistry data, suggests that the abnormal expression of blood type
      antigens in the colon may be a unique and essential factor for colonic CD.

PMID- 21725904
TI  - Conductive carbon tape as a sample platform for microwave-based MALDI MS
      detection of proteins and phosphoproteins.
AB  - In this study, we developed a novel microwave-assisted protein preparation and
      digestion method for matrix-assisted laser desorption/ionization (MALDI) time-of
      flight mass spectrometry analysis and identification of proteins that involves
      using conductive carbon tape as a sample platform for sample preparation
      (reduction and alkylation) and digestion under microwave heating and as a plate
      for MALDI analysis. This method allows for the enzymatic digestion products of
      proteins to be directly analyzed by MALDI mass spectrometry and results in a
      marked reduction in sample loss. Our protocol requires only a small volume (1
      MUL) of reaction solvent, which increases the frequency of enzyme-to-protein
      contact, thereby resulting in more efficient digestion of sample than
      conventional in-solution digestion methods. To test this protocol, we used
      magnetic iron (II, III) oxide nanoparticles as concentrating probes to enrich
      phosphopeptides from a mixture of peptides in enzymatically digested protein
      samples. We found that the one-pot on-tape-based protein preparation and
      digestion under microwave heating combined with the on-tape-based enrichment
      method not only dramatically reduced the time required for phosphopeptides
      analysis but also allowed for the simultaneous identification of phosphoproteins.
      The advantages of our protocol include ease of use, high digestion efficiency,
      high specificity, and rapid (15 min) identification of proteins and enrichment of
      phosphopeptides in a mixture of enzymatically digested protein samples.

PMID- 21725905
TI  - Human Angiostrongylus cantonensis: an update.
AB  - Angiostrongylus cantonensis was first discovered in 1935 and has become an
      important emerging pathogen causing human angiostrongyliasis. Major outbreaks of
      human angiostrongyliasis have been reported in endemic regions. Thousands of
      cases of human angiostrongyliasis have been documented worldwide. A. cantonensis
      has spread from its traditional endemic regions of the Pacific islands and
      Southeast Asia to the American continent including the USA, Caribbean islands and
      Brazil. Humans acquire A. cantonensis by consumption of raw or undercooked
      intermediate snail hosts or paratenic hosts. The main clinical manifestations of
      human angiostrongyliasis are eosinophilic meningitis and ocular
      angiostrongyliasis. The treatment of this disease includes supportive treatment,
      corticosteroid therapy, and combined therapy with corticosteroids and
      anthelminthics. The most effective method for prevention is to persuade people
      not to eat raw or undercooked intermediate and paratenic hosts.

PMID- 21725906
TI  - Pharmacological activation of peroxisome proliferator-activated receptor delta
      improves insulin resistance and hepatic steatosis in high fat diet-induced
      diabetic mice.
AB  - The mechanisms regarding hepatic steatosis related to hepatic insulin resistance
      have been well documented. However, the agents for treatment of hepatic steatosis
      and insulin resistance remain poorly developed. Peroxisome proliferator-activated
      receptors (PPARs) are transcription factors that are responsible for the
      regulation of glucose and/or lipid metabolism. There are 3 distinct isoforms of
      PPARs family: PPARalpha, PPARgamma, and PPARdelta. Both PPARalpha and PPARgamma
      agonists are widely used in clinic for the treatment of hyperlipidemia and
      hyperglycemia. However, the therapeutic efficacy of PPARdelta agonists for
      diabetic disorders remains obscure. In the present study, we used L-165041 as
      PPARdelta agonist to treat the high fat diet (HFD) fed mice. Administration of L
      165041 improved the hepatic steatosis and increased the insulin sensitivity in
      HFD-mice. In addition to the histological identification of hepatic steatosis,
      the improvement of insulin sensitivity was characterized by the enhanced insulin
      signals and the increase of hepatic glycogen content. This is the first report
      showing that pharmacological activation of PPARdelta improves insulin resistance
      in diet-induced diabetic mice. Thus, we suggest that pharmacological activation
      of PPARdelta may be a new strategy for the treatment of diabetic patients with
      hepatic steatosis.

PMID- 21725907
TI  - [Interventional radiological therapies in lung oncology].
AB  - Interventional radiological procedures for the treatment of primary and secondary
      pulmonary malignancies have become increasingly important. In addition to
      thermally ablative treatment, selective chemoembolisation by a vascular access
      allows localised therapy. These treatments are considered to be palliative for
      patients in a reduced general condition which does not allow systemic
      chemotherapy. In functionally inoperable patients especially the ablative
      procedures are potentially curative alternatives to surgery. This article
      provides an overview of the currently used interventional radiological procedures
      in lung oncology and assesses their importance. Further studies are needed to
      show whether interventional radiological procedures, which are promising due to
      their favourable risk-benefit ratio, may represent an alternative to radiotherapy
      or be effective in multimodal approaches.

PMID- 21725908
TI  - [Extrapulmonary small-cell lung cancer].
AB  - We report on a 61-year-old male patient who was admitted due to dysphagia,
      hoarseness and stridor. CT showed extensive metastasis to the thyroid and left
      adrenal gland. Histology revealed small-cell lung cancer. A primary tumour could
      not be detected in the lungs and mediastinum. Good symptom control could be
      achieved by administration of platinum-based chemotherapy.

PMID- 21725909
TI  - [Gorham-Stout syndrome--a case report].

PMID- 21725910
TI  - [Gugging - different stories about a different facility].

PMID- 21725911
TI  - [The 10 most important questions of social sciences in the 21st century].

PMID- 21725916
TI  - [Psychiatry in Transcarpathia, Ukraine].

PMID- 21725917
TI  - Plasma pentraxin-3 as a marker of bioincompatibility in hemodialysis patients.
AB  - INTRODUCTION: Hemodialysis (HD)-induced inflammation has a pathogenetic role in
      patients with end-stage renal disease (ESRD). The aim of the present study was to
      assess whether pentraxin-3 (PTX3) could be a reliable biomarker of HD-induced
      inflammation and of membrane biocompatibility. METHODS: We prospectively enrolled
      31 HD patients. Blood samples for determining PTX3, C-reactive protein (CRP),
      leukocytes and neutrophils were drawn from the arterial needle, before dialysis
      after the long dialysis-free interval (time 0), at the end of the index session
      (time 1) and before the next dialysis session (time 2). In 22 of 31 patients, 30
      minutes after start of dialysis, PTX3 and CRP plasma levels were measured in
      blood collected from both the arterial and venous lines (time A - time V) of the
      dialyzer. In 7 of 22 patients intracellular PTX3 levels in neutrophils were
      measured at the end of session. RESULTS: PTX3 venous levels were significantly
      increased at the end of the index session compared with baseline and in blood
      samples drawn from the venous line compared with the arterial line of the
      dialyzer. At time 1, a reduction of intracellular PTX3 in neutrophils was
      noticed. In contrast, CRP plasma levels were stable during the HD session.
      CONCLUSIONS: Our findings suggest that PTX3, which is rapidly produced by several
      cell types and released by neutrophils upon stimulation, could be a biomarker of
      HD-induced inflammation and of blood-membrane bioincompatibility.

PMID- 21725918
TI  - Identification of quantitative trait loci for diabetic nephropathy in KK-Ay/Ta
      mice.
AB  - BACKGROUND: The pathogenesis and development of human diabetic nephropathy
      involves genetic factors. Since human diabetic nephropathy is a heterogeneous
      disorder, identification of responsible gene loci is difficult. We studied
      candidate gene loci for diabetic nephropathy, using quantitative trait locus
      (QTL) analysis of a spontaneous animal model for diabetic nephropathy: KK-Ay/Ta *
      normal BALB/cA F2 intercross mice. METHODS: We examined 270 (KK-Ay/Ta * BALB/cA)
      F2 intercross mice for their urinary albumin to creatinine ratios (ACRs), HbA1c
      and fasting body weights (FBW) at 8, 12, 16 and 20 weeks. Genotypes were
      investigated using 86 microsatellite markers with QTL analysis. RESULTS: ACR in
      mice at 20 weeks and ACR gain showed a suggestive linkage to chromosome 9 (log of
      the odds [LOD] scores: 3.8 and 3.4, respectively; designated ACR-1). Gene loci
      contributing to HbA1c indicated a significant linkage to chromosome 7 (LOD: 5.8
      and 8.9) in mice at 8 and 20 weeks (designated HbA1c-1), and FBW indicated a
      significant linkage to chromosome 1 (LOD: 5.5 and 5.2) in mice at 8 and 12 weeks
      (designated Fbw-1). At 20 weeks, glomerular to Bowman's capsule volume (G/B)
      ratio of F2 mice homozygous BB for D9Mit66 was significantly higher than that in
      homozygous KK and heterozygous KB F2 progeny. The sizes of pancreatic islets in
      F2 progeny homozygous KK and heterozygous KB for D7Mit100 were larger than those
      in homozygous BB F2 progeny. CONCLUSION: QTL analysis of KK-Ay/Ta mice revealed
      several new loci contributing to diabetic nephropathy and related phenotypes.
      Thus, it appears that type 2 diabetes and nephropathy of KK-Ay/Ta mice have
      different genetic factors.

PMID- 21725919
TI  - Graft loss risk in renal transplant recipients with metabolic syndrome: subgroup
      analyses of the ALERT trial.
AB  - BACKGROUND: Several nonimmunologic risk factors for late renal graft loss (RGL)
      are also known components of metabolic syndrome (MS). We aimed to study MS as a
      risk factor for RGL. Also, the effect of statin treatment in reducing renal risk
      in renal transplant recipients (RTRs) with MS was studied. METHODS: Nondiabetic
      RTRs (n=1,706) from the ALERT trial were followed for 7-8 years. MS was defined
      according to National Cholesterol Education Program Adult Treatment Panel III
      definition with waist girth replaced by BMI >=30 (calculated as kg/m(2)). Renal
      end points included death-censored RGL and graft loss or doubling of serum
      creatinine. RESULTS: During the follow-up, 284 patients experienced RGL, and
      there were 343 cases of graft loss or doubling of serum creatinine. Those with MS
      had increased risk for RGL (relative risk = 1.28, 95% confidence interval, 1.00
      1.63; p=0.047), but not for the combined end point. After adjustment for other
      known and potential risk factors, MS was no longer associated with increased risk
      for RGL. The association between MS and RGL risk was attenuated once adjustment
      for creatinine was made. Statin treatment did not reduce the risk for renal end
      points in RTRs with or without MS. CONCLUSION: MS had no independent association
      with RGL risk. Adjustment for renal function attenuated the association between
      MS and RGL.

PMID- 21725920
TI  - Nrf2 and Sp family synergistically enhance the expression of ion transporters in
      potassium-depleted conditions.
AB  - INTRODUCTION: During potassium (K) depletion, many adaptive responses are likely
      mediated through a complex network that involves expression of a variety of
      genes. We identified that the Nrf2 gene was differentially expressed between
      normal and K-depleted rat kidney. METHODS: To investigate the effect of Nrf2 on
      colonic H/K-ATPase and kNBC1, overexpression of Nrf2 was carried out in 293T and
      CV1 cell lines, and experiments were conducted in low-K media. Sp family was
      cotransfected with Nrf2 to examine the relationship between the 2 molecules and
      their effect on ion transporters. RESULTS: Ion transporters were activated by
      overexpression of Nrf2 and cotransfection of Nrf2 with Sp family genes showed
      additional enhancement of colonic H/K-ATPase and kNBC1 expression and their
      promoter activities. Pretreatment with low-K media increased the transcriptional
      activity of Nrf2, colonic H/K-ATPase and kNBC1. Furthermore, transfection of
      dominant-negative Nrf2 completely abolished low-K-mediated expression of the ion
      transporters. CONCLUSION: These results suggest that Nrf2 mediates
      transcriptional activation of colonic H/K-ATPase and kNBC1 in response to K
      depleted stress and augments Sp family-mediated expression of these ion
      transporters.

PMID- 21725921
TI  - Long-term effects of methylprednisolone pulses and mycophenolate mofetil in IgA
      nephropathy patients at risk of progression.
AB  - BACKGROUND: IgA nephropathy (IgAN) is a microcosm of glomerular lesions. Some
      histologic lesions are irreversible and progress toward obliteration of
      glomerular capillaries. Others are acute inflammatory processes potentially
      susceptible to reversal by means of immunosuppressive therapies. METHODS: The
      effects of a combined schedule of steroids and mycophenolate mofetil (MMF) was
      prospectively examined in a subset of IgAN patients with acute inflammatory
      histologic changes associated with proteinuria (mean 2,400 mg/day, range 1,130
      5,250), hematuria (76 red cells per high-power microscopic field, range 30-100)
      and renal failure (serum creatinine 1.6 mg/dL, range 1.2-2.9). Patients had
      diffuse mesangial proliferation with at least 10% florid crescents, mild to
      moderate degrees of glomerular sclerosis and interstitial changes, and both
      mesangial and capillary deposition of immunoreactants at immunofluorescence.
      Treatment consisted of 3 pulses of methylprednisolone (15 mg/kg) followed by oral
      prednisone (0.8 mg/kg body weight, tapered until discontinuation within 4 months)
      and MMF 2 g for 6 months. RESULTS: Serum creatinine, proteinuria and microscopic
      hematuria significantly dropped at 6 months compared with baseline values
      (p=0.01) and remained lower at the end of follow-up 51 months (range 24-90) later
      (p<0.01, for proteinuria and hematuria; p=0.08, for serum creatinine).
      CONCLUSION: Therapy with steroids and MMF may be considered in a subset of IgAN
      patients with florid glomerular changes, functional impairment and major urinary
      abnormalities, to prevent subsequent progression toward renal failure.

PMID- 21725922
TI  - Renal histology in the elderly: indications and outcomes.
AB  - BACKGROUND: Renal disease is being increasingly diagnosed in the elderly.
      However, reports on biopsy-confirmed renal disease in this population are
      limited. The aim of this study was to give an overview of the most important
      indications, diagnoses and outcomes of renal biopsies in the elderly in our
      center. METHODS: This was a retrospective review of all elderly renal biopsies
      over 5 years. Patients were eligible for inclusion if they were aged >=65 years
      and had had a native kidney biopsy performed. The data recorded included age,
      sex, indications for biopsy, histological diagnoses and outcomes. RESULTS: During
      this time, 1,372 native renal biopsies were performed. Of these, 236 (17%) were
      in patients aged >=65 years; 150 male (64%) and 86 female (36%). The most common
      indications for biopsy were acute renal failure and nephrotic syndrome. Common
      diagnoses included pauci-immune crescentic glomerulonephritis, tubulointerstitial
      nephritis, membranous nephropathy, IgA nephropathy and chronic thrombotic
      microangiopathy. Long-term follow-up of 3 years was available for 102 patients;
      median serum creatinine at the time of biopsy was 427 umol/L (interquartile range
      204-702) and at 3 years post biopsy had fallen to 192 umol/L (interquartile range
      152-408). CONCLUSIONS: In our center, 17% of native kidney biopsies are performed
      in elderly patients aged >=65 years. In our experience, this procedure was safe
      and had a 97% diagnostic rate. The available follow-up data of patients suggest
      that renal histology is not only of benefit in diagnosis but also of potential
      value in terms of prognosis and treatment.

PMID- 21725923
TI  - Does chronic kidney disease modify the association between body mass index and
      cardiovascular disease risk factors.
AB  - BACKGROUND: Excess weight is paradoxically associated with better cardiovascular
      disease (CVD) outcomes and mortality in end-stage renal disease (ESRD) patients
      treated with hemodialysis. This association has been observed in chronic kidney
      disease (CKD) as well. One potential explanation for this inverse relationship is
      that the usual positive correlation between severity of CVD risk factors and
      higher body mass index (BMI) is reversed in CKD. To test this hypothesis, we
      determined the relationship between BMI and CVD risk factors in patients with and
      without CKD. METHODS: This was a cross-sectional study of the nationally
      representative US National Health and Nutrition Examination Survey (NHANES) 1999
      2006. CKD was defined as glomerular filtration rate <60 ml/min per 1.73 m2.
      Covariates were age, race/ethnicity, sex and use of relevant prescription
      medications. Outcome variables were total cholesterol, LDL cholesterol, HDL
      cholesterol, triglycerides, systolic blood pressure (SBP), diastolic blood
      pressure (DBP), C-reactive protein (CRP) and fasting glucose (FG). RESULTS: There
      were 1,895 and 32,431 patients with and without CKD, respectively. Those with CKD
      were older and had higher BMI. The shapes of the association between BMI and
      total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, SBP, CRP and
      FG were similar in those with or without CKD. In a sensitivity analysis excluding
      patients taking relevant prescription medications, our results did not differ
      substantially. CONCLUSIONS: CKD did not alter the shapes of the association
      between higher BMI and CVD risk factors. Inverse associations between BMI and CVD
      risk factors are unlikely to explain why CKD patients with higher BMI may have
      better outcomes.

PMID- 21725924
TI  - Expression of transcription factor Snai1 and tubulointerstitial fibrosis in
      progressive nephropathy.
AB  - BACKGROUND: Tubulointerstitial fibrosis (TIF) is seen as the final stage of
      progressive nephropathy, and the degree of TIF is reported to be a major
      determinant in renal outcomes. In recent years, epithelial-mesenchymal transition
      (EMT) and the zinc-finger transcription factor snail homolog 1 (Snai1) have each
      been implicated in the mechanism of TIF. The relationship between EMT and these
      transcription factors is unclear, however, so in this study we attempted to
      elucidate the correlation between the expression of Snai1 and clinical markers.
      METHODS: We performed immunohistochemical staining on human renal tissue obtained
      from patients with diabetic nephropathy (DN), IgA nephropathy (IgAN), minimal
      change disease (MCD) and minor glomerular abnormality (MGA) using anti-Snai1 and
      anti-vimentin antibodies. We counted Snai1-positive and Snai1/vimentin double
      positive tubular epithelial cells. RESULTS: Snai1 protein was mainly observed in
      the nuclei of flattened, damaged tubular epithelial cells, especially in IgAN and
      DN, and positive cell numbers were significantly higher in IgAN than in MGA, MCD
      or DN. Snai1/vimentin double staining showed that some vimentin-positive tubular
      epithelial cells also contained Snai1-positive nuclei, and double positive cell
      numbers were increased in IgAN and DN. Statistical analysis revealed positive
      correlations between Snai1/vimentin double positive cell numbers and proteinuria
      and creatinine in IgAN. Positive correlations were also seen between
      Snai1/vimentin double positive cell numbers and the severity of proteinuria in
      DN. CONCLUSIONS: The results of this study indicate that Snai1 plays an important
      role in TIF in patients with progressive nephropathy.

PMID- 21725925
TI  - Cardiac valve calcification is a marker of vascular disease in prevalent
      hemodialysis patients.
AB  - BACKGROUND: Vascular and valvular calcifications are a common finding in chronic
      kidney disease (CKD) patients and are associated with increased morbidity and
      mortality. We investigated the hypothesis that calcification of the cardiac
      valves is a marker of coronary artery calcification (CAC) and thoracic aorta
      calcification (AoC) in hemodialysis (CKD-5) patients. METHODS: This was a cross
      sectional study of 145 maintenance CKD stage 5 (CKD-5) patients. All patients
      underwent electron beam tomography for quantification of CAC and AoC score via
      the Agatston score. The presence of calcification of the cardiac valves was
      assessed by standard bi-dimensional echocardiography. RESULTS: Eighty-four of the
      study patients (58%) had echocardiographic evidence of valvular calcification. A
      significant and graded association between valvular calcification and CAC as well
      as AoC was detected. Patients with 1 or 2 calcified valves had a significantly
      greater likelihood of having a CAC score >1,000 (odds ratio [OR] = 5.94; 95%
      confidence interval [95% CI], 1.91-18.44; p=0.002; and OR=3.27; 95%CI, 1.36-7.88;
      p=0.007, respectively). Similarly, the presence of 1 or 2 calcified valves was
      associated with an eightfold and threefold increased probability of an AoC score
      greater than the third quartile, respectively. CONCLUSIONS: This cross-sectional
      analysis shows that calcification of the cardiac valves is closely associated
      with vascular calcification, an established marker of risk in prevalent
      hemodialysis patients.

PMID- 21725926
TI  - Increased apoptosis and expression of FasL, Bax and caspase-3 in human lupus
      nephritis class II and IV.
AB  - BACKGROUND: Apoptosis is involved in glomerular injuries leading to
      glomerulonephritis. However, the role of renal cellular apoptosis in the
      pathogenesis and progression of human lupus nephritis (LN) is controversial, and
      studies on the expression of apoptosis-related proteins, such as FasL, Bax and
      caspase-3, in different classifications of human LN renal tissues are limited.
      METHODS: Thirty-two samples of LN tissues, including 10 cases of class II and 22
      cases of class IV LN, and 5 cases of human normal renal tissues were obtained.
      Expression of FasL, Bax and caspase-3 proteins in LN tissues was examined by
      immunohistochemical staining. Apoptotic cells were evaluated by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
      RESULTS: Expression of FasL, Bax and caspase-3 and TUNEL-positive cells in
      glomerular parenchymal cells, renal tubular epithelial cells and interstitial
      inflammatory cells were higher in LN tissues compared with controls. Expression
      of Bax and caspase-3, but not FasL, was significantly higher in glomeruli of
      class IV LN than those of class II LN. The apoptotic cell count per glomerulus
      was significantly higher in class IV LN than class II LN (p<0.05). CONCLUSIONS:
      Increased apoptosis and the expression of FasL, Bax and caspase-3 in human LN
      suggest that apoptosis might be induced through pathways of these proteins in the
      pathogenesis process and play an important role in LN progression through Bax and
      caspase-3, but not FasL.

PMID- 21725927
TI  - Ultrafiltration intensification for achievement of dry weight and hypertension
      control is not always the therapeutic gold standard.
AB  - Extracellular volume excess is an important factor in the pathogenesis of
      arterial hypertension, and control of volume status by ultrafiltration and
      achievement of dry weight is considered as an essential therapeutical approach.
      In the present issue of the Journal of Nephrology, Curatola and coworkers present
      challenging data indicating that ultrafiltration intensification improves
      hypertension control but increases the risks for cardiovascular events, with
      peripheral arteriopathy as the principal complication. This is another challenge
      for determination of dry weight on the basis of blood pressure (BP) measurement.
      The reference BP is brachial blood pressure. Brachial blood pressure is lower
      than limb BP. In normal conditions, lower-limb BP (ankle blood pressure) is
      higher than brachial BP, and the so-called ankle-brachial systolic pressure index
      is between 0.9 and 1.3. An ankle-brachial index <0.90 indicates the presence of
      lower-limb arteriopathy, and it should be measured systematically in end-stage
      renal disease (ESRD) patients because a large proportion of these patients
      present asymptomatic peripheral arteriopathies. In these conditions, taking into
      account brachial BP to determine dry weight and BP control can lead to a decline
      in the perfusion pressure of the lower limbs, with dramatic clinical
      consequences. The study by Curatola et al (J Nephrol, 2011, present issue)
      illustrates that the therapeutic approach to cardiovascular risk and hypertension
      in ESRD patients is still challenging. It underlines the necessity of considering
      the pathophysiology and mechanisms associated with cardiovascular risk, instead
      of systematically applying a generally accepted "gold standard" approach.

PMID- 21725928
TI  - Platelet activation in heart failure patients supported by the HeartMate II
      ventricular assist device.
AB  - OBJECTIVE: Thromboembolic events have been observed in heart failure (HF)
      patients supported by long-term mechanical circulatory support (MCS) devices. It
      has been hypothesized that these adverse events may be the result of platelet
      activation associated with high rotational speeds common to axial flow pumps. In
      this study, markers of platelet activation were investigated in HF patients
      supported by a HeartMate II left ventricular assist device (LVAD). METHODS: The
      study group consisted of 34 HF patients supported by a HeartMate II axial flow
      LVAD implanted for destination therapy (DT). This patient population was 94% male
      (31 M, 3 F), supported by LVAD for 30 to 723 days (average 268 days), and with an
      anticoagulation regimen of Coumadin (0-8 mg daily dose) and aspirin (0-325 mg
      daily dose). Platelet adhesion markers (soluble P-selectin and solube CD40
      ligand), platelet count (PC), hematocrit (Hct), and creatinine (Cr) were
      measured. RESULTS: The soluble P-selectin marker was within normal platelet
      activity limits for all end points. The soluble CD40 ligand marker indicated
      platelet inactivity for all end points. Despite high shear stresses associated
      with a high-speed axial flow pump, the HeartMate II had no discernable effect on
      platelet activation. Current clinical doses of aspirin also appear to have little
      effect on platelet activation. Platelet count, hematocrit, and creatinine were
      normal in these patients over duration of support. CONCLUSIONS: There were no
      discernable changes in platelet activation markers soluble P-selectin and soluble
      CD40 ligand in HF patients support by HeartMate II LVAD independently of length
      of support, anti-platelet, and anti-coagulation regimens.

PMID- 21725929
TI  - Role of the hemodialysis vascular access type in inflammation status and monocyte
      activation.
AB  - PURPOSE: The aim of this study was to ascertain the role of different vascular
      access types in inflammatory status, monocyte activation, and senescence in
      hemodialysis patients. METHODS: We recruited 126 hemodialysis patients, including
      51 with arterovenous fistula (AVF), 32 with arterovenous graft (AVG), and 43 with
      tunneled cuffed catheters (TCC). In dialysis patients enrolled in the study and
      in a control group of 40 healthy subjects, we measured the serum levels of
      albumin, CRP, IL-6, and TNF-a, the expression of CD14, CD44, and CD32 on monocyte
      surface, and the percentage of monocytes exhibiting a senescent phenotype
      (CD14+CD32+). RESULTS: The patients with AVG compared to those with AVF had: a)
      higher levels of CRP and TNF-a; b) increased expression of CD14 and CD32 on
      monocyte surface, with no difference in CD44 expression; c) no difference in the
      percentage of CD14+CD32+ monocytes. In the comparison of TCC vs. AVF group, we
      observed significantly higher values of: a) circulating inflammatory markers
      (CRP, IL-6, TNF-a); b) monocyte surface expression of cellular activation markers
      (CD14, CD44 and CD32); c) relative count of CD14+CD32+ monocytes. When comparing
      TCC vs. AVG group, we found: a) no difference in serum levels of CRP, IL-6, and
      TNF-a; b) no difference in the expression of CD14, CD44, and CD32 on monocyte
      surface; c) no difference in the percentage of CD14+CD32+ monocytes. CONCLUSIONS:
      These results suggest that the use of AVG and TCC for dialysis vascular access is
      associated with serological and cellular indexes of inflammatory reaction, also
      resulting in a higher degree of monocyte activation and senescence.

PMID- 21725930
TI  - Glucose but not N-acetylglucosamine accelerates in vitro senescence of human
      peritoneal mesothelial cells.
AB  - BACKGROUND: Preservation of the mesothelial cells (MCs) is crucial for longevity
      of the peritoneal dialysis membrane. Glucose accelerates aging of MC and we
      tested whether N-acetylglucosamine (NAG) has an identical effect. METHODS:
      Replicative aging of MCs was studied during 10 passages performed every three
      days in cells cultured in standard medium or in medium supplemented with Glucose
      30 mmol/L or NAG 30 mmol/L. Changes in population doubling time and beta
      galactosidase activity were used as an index of aging and compared with other
      cellular parameters. RESULTS: Repeated passages of MC cause their aging, as
      reflected by prolongation of the population doubling time, increased beta
      galactosidase activity, oxidative stress and release of cytokines. Healing of
      injured mesothelial monolayer is impaired in senescent cells. Glucose accelerates
      in vitro aging of MC, whereas NAG does not cause this effect. CONCLUSIONS:
      Replacement of glucose with NAG in the dialysis fluid can slow down aging of MC.

PMID- 21725931
TI  - An ex vivo platform to simulate cardiac physiology: a new dimension for therapy
      development and assessment.
AB  - PURPOSE: Cardiac research and development of therapies and devices is being done
      with in silico models, using computer simulations, in vitro models, for example
      using pulse duplicators or in vivo models using animal models. These platforms,
      however, still show essential gaps in the study of comprehensive cardiac
      mechanics, hemodynamics, and device interaction. The PhysioHeart platform was
      developed to overcome these gaps by the ability to study cardiac hemodynamic
      functioning and device interaction ex vivo under in vivo conditions. METHODS:
      Slaughterhouse pig hearts (420 +/- 30 g) were used for their morphological and
      physiological similarities to human hearts. Hearts were arrested, isolated and
      transported similar to transplantation protocols. After preparation, the hearts
      were connected to a special circulatory system that has been engineered using
      physical and medical principles. Through coronary reperfusion and controlled
      cardiac loading, physiological cardiac performance was achieved while hemodynamic
      parameters were continuously monitored. RESULTS: Normal cardiac hemodynamic
      performance was achieved both qualitatively, in terms of pulse waveforms, and
      quantitatively, in terms of average cardiac output (4 l/min) and pressures
      (110/75 mmHg). Cardiac performance was controlled and kept at normal levels for
      up to 4 hours, with only minor deterioration of hemodynamic performance.
      CONCLUSIONS: With the PhysioHeart platform we were able to reproduce normal
      physiological cardiac conditions ex vivo. The platform enables us to study, under
      different but controlled physiological conditions, form, function, and device
      interaction through monitoring of performance parameters and intra-cardiac
      visualization. Although the platform has been used for pig hearts, application of
      the underlying physical and engineering principles to physiologically comparable
      hearts from different origin is rather straightforward.

PMID- 21725932
TI  - Microseparation and stripe wear in alumina-on-alumina hip implants.
AB  - The combination of materials that still has highest wear resistance for total hip
      replacement is ceramic-on-ceramic. However, brittleness is a major concern for
      ceramics: in vivo and in vitro studies on ceramic hip prostheses correlate
      microseparation with hip noise, ceramic wear, or ceramic liner damage. Ceramic
      microseparation can lead to edge load, ceramic head wear, and squeaking. The aim
      of this in vitro study was to investigate whether different angles of inclination
      influence the wear pattern of alumina-on-alumina hip joints with micro-separation
      during the swing phase. We also evaluated the wear rate obtained from this in
      vitro investigation with retrieval specimens obtained at 13 years' mean follow
      up. The study was performed using a 12-station hip joint wear simulator (Shore
      Western, Monrovia, CA, USA) under bovine calf serum used as lubricant. Wear was
      evaluated by the gravimetric method and the test length was set at two million
      cycles. After two million cycles, a volumetric loss of 0.11 +/-0.03 mm3 and 0.12
      +/-0.06 mm3 was observed, respectively, for 23 degrees  and 63 degrees  angles of
      inclination. In particular, the results obtained in this work revealed an
      increase of about 12-fold compared to previous results without microseparation
      conditions. No significant differences were observed between the two different
      inclinations on the wear patterns of the acetabular cups with a level of
      significance of a = 0.5. The location and general shape of the stripes wear were
      similar for the retrieved and simulator balls.

PMID- 21725933
TI  - Pulsatile perfusion preservation for expanded-criteria donors kidneys: Impact on
      delayed graft function rate.
AB  - PURPOSE: Expanded criteria donors (ECD) kidneys are a potential solution to organ
      shortage, but exhibit more delayed graft function (DGF). We conducted a
      prospective controlled study aiming to evaluate the impact of pulsatile perfusion
      preservation (PPP) on DGF rate. METHODS: Inclusion criteria were: 1) ECD
      definition (any brain-dead donor aged > 60 years or aged 50-60 years with at
      least 2 of the following: history of hypertension, terminal serum creatinin level
      = 1.5 mg/dL, death resulting from a cerebrovascular accident; 2) Donor prolonged
      circulatory arrest (> 20 mn); 3) previsible cold ischemia time longer than 24
      hours. In each pair of kidneys, one organ was preserved with PPP and the other
      organ was preserved in static cold storage. RESULTS: From February 2007 to
      September 2009, a total of 22 donors (44 recipients) were included. Recipients
      were comparable in the two groups with respect to demographic and immunological
      data. The rate of DGF was significantly lower (9% vs. 31.8%, p = 0.021) in the
      PPP group. At 1, 3, and 12 months, renal function was comparable in the two
      groups. CONCLUSIONS: Pulsatile perfusion preservation significantly reduced DGF
      rate in ECD kidney transplantation.

PMID- 21725934
TI  - Pancreatic islets from non-heart-beating donor pig: two-layer preservation method
      in an in vitro porcine model.
AB  - PURPOSE: Pancreata from non-heart beating donors could represent an unlimited
      source of islets if their cell viability can be efficiently preserved during the
      time necessary to process the organs by the use of a better solution of
      preservation compared to the classic University of Wisconsin solution. The aim of
      this study was to determine whether it is possible to obtain functioning "alive
      islets" from non-heart-beating donors by comparing, on a porcine model, the
      classic "UW ice-store" method with a two-layer cold storage method (TLM) using
      oxygenated Perfluorocarbons (PFC) and UW. METHODS: Whole pancreata were harvested
      from 20 NHBDs female pigs with similar characteristics and preserved for 4 h in
      UW solution (n = 10) or TLM (UW/PFC) solution (n=10). The isolated islets were
      then evaluated for number, viability, purity, and insulin secretion, also
      estimated after 8 weeks of cryopreservation. RESULTS: The total number of islets
      obtained from isolation, and their function assayed by the insulin stimulation
      index, before and after cryopreservation, showed a higher value in the TLM group.
      No significative differences in terms of purity and viability before and after
      cryopreservation were found when comparing the two groups. CONCLUSIONS: TLM
      solution for NHBDs porcine pancreata with cold ischemia time lower than 4 h
      offers significant advantages over UW solution storage, thereby increasing the
      isolation yield and isolation success rate of the pancreatic porcine islets.

PMID- 21725935
TI  - Effect of mitomycin C on success rate in dacryocystorhinostomy with silicone tube
      intubation and improper flaps.
AB  - PURPOSE: To assess the effect of mitomycin C on surgical success rate of
      dacryocystorhinostomy and silicone intubation in patients with improper flaps.
      METHODS: The study was a randomized clinical trial. The patients with indication
      for dacryocystorhinostomy surgery with silicone intubation (inappropriate
      lacrimal sac or nasal mucosal flaps during surgery and/or history of
      dacryocystitis in the past 3 months) were randomly assigned to application of
      mitomycin C (0.02%) on surgical flaps (group A) or a control group without
      mitomycin C application (group B). Main outcome measures were subjective
      symptomatic improvement and result of irrigation test at last follow-up visit.
      RESULTS: The study enrolled 88 patients (88 eyes); there were 42 patients in
      group A and 46 patients in group B. There was an average follow-up of 10 months
      (range 6-15 months) following surgery. Significant improvement (no tearing with
      patent lacrimal system in irrigation) was observed in 31 patients (73.8%) in
      group A and 32 patients (69.6%) in group B. There was no statistically
      significant difference in no improvement (no change in tearing state and
      obstruction in irrigation test), relative improvement (decreased tearing and
      passage of fluid with force in irrigation test), and significant improvement rate
      between the 2 groups of study (p>0.05). CONCLUSIONS: Application of mitomycin C
      on surgical flaps during dacryocystorhinostomy surgery with silicone intubation
      in patients with improper flaps has no proven beneficial effect on success rate
      of surgery.

PMID- 21725936
TI  - Ultrasound biomicroscopy findings in fireworks-related blunt eye injuries.
AB  - PURPOSE: To present ultrasound biomicroscopic (UBM) findings and their clinical
      correlations in people with optically hazy media after injury at the Persian
      Wednesday Eve fireworks festival. METHODS: Ultrasound biomicroscopy was performed
      on a series of 32 eyes with severe closed-globe injuries by P40 ultrasound
      biomicroscope. RESULTS: The median age of the participants was 19 years, and
      81.3% were male. All but one had gross hyphema. Seventy-five percent had an
      extension of the injury (at least) to Birmingham Eye Trauma Terminology zone II.
      Ultrasound biomicroscopy detected 3 more iridodialyses and 10 more cyclodialyses
      in addition to the respective 5 and 3 that were diagnosed clinically. Ten cases
      of angle recession were observed, and 5 were suggestive of subluxation of the
      crystalline lens. Two cases were suspected for anterior segment intraocular
      foreign body on clinical examination, but UBM and computed tomography scanning
      together ruled out such a diagnosis. CONCLUSIONS: Our study showed the value of
      UBM in the assessment of severely contused eyes and hyphema. It made possible
      evaluation for dialyses and recessions at presentation. Ultrasound biomicroscopy
      illustrated diverse subclinical disruptions in clinically invisible anterior
      segment structures.

PMID- 21725937
TI  - Topical cyclosporine A administration after pterygium surgery.
AB  - PURPOSE: To evaluate the success rate of topical cyclosporine A (tCsA) (Restasis,
      Allergan) in preventing the recurrence of pterygium excision and conjunctival
      flap rotation technique in patients applying to our clinic and diagnosed with
      pterygium. METHODS: A total of 56 eyes with primary pterygium in 56 patients were
      examined and operated with pterygium excision and conjunctival flap rotation
      technique between October 2008 and September 2009. A total of 26 eyes of these 56
      patients were treated with tCsA (Restasis, Allergan) for 6 months during the
      postoperative period and assigned as the treatment group. The other 30 eyes of 56
      patients were assigned as the control group. The operated patients were followed
      up for approximately 11 months. RESULTS: The 2 groups were similar in age, sex,
      and pterygial size. The largest percentage of the patients were farmers (30.3%).
      The pterygium recurred in 8 (14.2%) of 56 patients; 2 of them were in the
      treatment group (7.7%) and 6 of them were in the control group (20.0%). There was
      not any complication threatening vision among operated patients. Recurrence rates
      between the control and treatment group were statistically significant (p<0.05).
      The complication and postoperative compliance rates were lower in the treatment
      group than the control group. The difference between preoperative and
      postoperative Schirmer I test results among the treatment and control group was
      statistically significant (p<0.05). The Schirmer I test results increased after
      tCsA treatment for patients assigned to the treatment group. CONCLUSIONS: The
      results suggest that tCsA (Restasis, Allergan) can be used safely and effectively
      after pterygium surgery to obtain lower rates of recurrence.

PMID- 21725939
TI  - 18FDG-PET/CT assessing the absence of cell viability and excluding metastatic
      disease in a case of necrotic choroidal melanoma.
AB  - PURPOSE: To report a case of choroidal melanoma in which the absence of 18FDG
      positron emission tomography (PET)/computed tomography (CT) uptake in the whole
      body scan excluded the presence of any foci of metastases. Additionally, the
      PET/CT study correctly diagnosed the necrotic character of the lesion. METHODS: A
      76-year-old woman with neovascular glaucoma, and without vitreous or retina
      visualization, was studied by our ophthalmology service. RESULTS: Ocular
      ultrasound showed an 18 * 16 mm vitreous exophytic image compatible with
      choroidal melanoma; magnetic resonance gave a 17 * 15 mm exophytic image, highly
      intense at T1 and hypointense at T2, with cystic and necrotic images after a
      contrast injection. An 18FDG-PET/CT study revealed a clearly hypometabolic
      lesion, representing absence of cell viability and excluding active melanoma
      cells. No other uptake lesions were detected at the whole-body PET/CT scan,
      assuming the absence of extraocular metastases. The eye was enucleated, and the
      pathology study showed a 16 * 15 mm necrotic choroidal melanoma. CONCLUSIONS: The
      18FDG-PET/CT study correctly depicted the necrotic character of the choroidal
      melanoma and was able to exclude other foci of metastases.

PMID- 21725940
TI  - Phacoemulsificator and sterile drapes contamination during cataract surgery: a
      microbiological study.
AB  - PURPOSE: To determine the microbial contamination of the irrigating fluids at the
      time of phacoemulsification after the use of topical povidone-iodine and
      antibiotics prophylaxis. METHODS: A total of 119 patients undergoing cataract
      surgery were enrolled in this prospective study. All patients received 5 mg/mL
      levofloxacin starting from the day prior to surgery and topical and 5% povidone
      iodine drops starting from 30 minutes before the surgery. At the end of each
      surgery, 2 samples of drainage liquids were sterilely collected from the drainage
      bags (DBL) and from the peristaltic pump single-cassettes (PCL) of the
      phacoemulsification machine. Search for aerobic and anaerobic bacteria and fungi
      was performed. RESULTS: Seventy-five patients (31.5%) revealed a growth of at
      least one microbial species (53 DBL and 22 PCL, 44.5% vs 18.5%; p<0.001). Sixty
      six patients (55.5%) had at least one positive intraoperative solution. Overall,
      111 microbial strains were collected: 82 (74%) Gram-positive bacteria, 20 (18%)
      fungi, and 9 (8%) Gram-negative bacteria. Thirteen staphylococcal isolates from
      PCL, compared with 52 out of DBL (11% vs 43.7%, p<0.001), fungi were essentially
      isolated from PCL. No significant correlation was found between microbial
      isolation and risk factors. No postsurgical infective complication occurred in
      the follow-up. CONCLUSIONS: Evaluation of intraoperative fluids can provide
      evidence on sources or vehicles of postsurgical infections. Antibiotic
      prophylaxis and topical povidone-iodine can significantly contribute to minimize
      the risk of endophthalmitis.

PMID- 21725942
TI  - Horizontal rectus surgery in Duane syndrome.
AB  - PURPOSE: To study the results of horizontal rectus recession for treatment of
      Duane syndrome. METHODS: This was a retrospective study of 17 patients with Duane
      syndrome who underwent strabismus surgery between 2000 and 2008 with medial
      rectus recession for esotropic deviation or lateral rectus recession for
      exotropic deviation. The amount of surgery varied individually with the angle of
      deviation and abnormal head posture. Head turn was graded as mild, moderate, or
      severe. Botulinum toxin was injected in specific cases. An angle of deviation
      less than 10 PD and head turn less than 5o after surgery were considered good
      results. RESULTS: Treatment was successful in 12 cases (70.58%) and unsuccessful
      in 5 (4 with type I Duane syndrome and one with type III Duane syndrome); in 3
      patients the deviation was undercorrected and 2 it was overcorrected. Ipsilateral
      medial rectus recession of less than 5 mm was performed in 12 patients, although
      1 case with a recession of 7 experienced secondary adduction limitation.
      Abduction limitation was slightly improved in 29.41%. Mean follow-up was 50.59
      months. CONCLUSIONS: Moderate horizontal rectus recession is a simple and
      effective procedure in most patients with Duane syndrome and no secondary duction
      limitations. The technique only slightly improved abduction in one-third of the
      cases.

PMID- 21725943
TI  - Adenoid cystic carcinoma of the lacrimal gland: CT and MRI findings.
AB  - PURPOSE: To highlight the computed tomography (CT) and magnetic resonance imaging
      (MRI) characteristics of lacrimal gland adenoid cystic carcinoma. METHODS: We
      reviewed the clinical records and imaging findings of 17 patients who were
      histopathologically diagnosed with primary adenoid cystic carcinoma of the
      lacrimal gland between August 1998 and November 2010. Orbital CT scans were
      performed in 17 patients and MRI scans were obtained in 13 patients. RESULTS: On
      the CT scans, out of 4 cases of adenoid cystic carcinoma, 3 showed characteristic
      features of a soft tissue mass with poorly enhancing areas representing cystic
      changes, and 4 of 17 cases had contiguous bony erosion. On the MRI scans, all
      cases had mixed signal intensity on T2-weighted images, and 6 cases showed poorly
      enhancing areas. CONCLUSIONS: Enhanced CT and MRI (including T2-weighted) are
      helpful in the diagnosis of primary adenoid cystic carcinoma of the lacrimal
      gland.

PMID- 21725944
TI  - Quantitative ultrasound biomicroscopy study of biometry of the lens and anterior
      chamber.
AB  - PURPOSE: To quantify the changes induced by cataract extraction (CE) in angle
      recess area (ARA), angle opening distance at 250 and 500 um (AOD250, AOD500), and
      aqueous depth (AQD) in comparison with axial lens thickness (LT) and to reveal
      effects of LT and lens position (LP) on angle parameters and AQD using ultrasound
      biomicroscopy (UBM). METHODS: Thirty-five eyes of 35 patients (22 male; mean age
      69.5 +/- 7.8 years) with senile or presenile cataract who consecutively underwent
      cataract surgery were enrolled in this institutional study. We performed UBM
      examinations before and 1 month after surgery under a standard protocol. Axial
      images of the anterior segment and radial sections of the angle at 4 quadrants
      were obtained. Aqueous depth and LT were measured in immersion A-scan mode and we
      used UBM Pro 2000(r) software for the ARA, AOD250, and AOD500. RESULTS: Aqueous
      depth and angle parameters at 4 quadrants were increased significantly after CE
      (p<0.05). The mean LT was 4.53 +/- 0.37 mm and LP was 4.96 +/- 0.25 mm
      preoperatively. There were statistically significant correlations between LT, LP,
      and AQD and angle parameters preoperatively. We also determined statistically
      significant correlations between LT, LP, and postoperative changes in AQD and
      angle parameters In comparison with LT, the mean increases in AQD, ARA, AOD250,
      and AOD500 were 0.21, 0.014, 0.012, and 0.017 times, respectively. CONCLUSIONS:
      The results suggest that LT is as a significant factor as LPon the final
      dimensions of the anterior chamber and angle.

PMID- 21725945
TI  - Radial artery pseudoaneurysm after coronary angioplasty.

PMID- 21725946
TI  - Experience with ulcerated, bleeding autologous dialysis fistulas.
AB  - PURPOSE: The incidence of ulcerated, bleeding, autologous, hemodialysis fistulas
      has been felt to be increasing in recent years. This review was undertaken to
      examine our experience with patients who presented with episodes of spontaneous
      bleeding in the presence of an ulcerated lesion over their autologous dialysis
      accesses. METHODS: A database of hemodialysis access procedures was reviewed for
      individuals with spontaneous bleeding from ulcerations. Twenty-four patients were
      identified with 28 ulcerating lesions over a ten-year period from 2001 to 2011.
      Each had at least a single episode of spontaneous bleeding. Treatment methods
      were reviewed including five techniques of surgical intervention. RESULTS: Two of
      24 patients expired from major hemorrhagic events before obtaining surgical
      consultation (8.3%). Twenty-one patients (87.5%) underwent 28 surgical procedures
      for correction of the ulcers. One patient (4.1%) with simultaneous ulcers healed
      under antibiotic therapy during close observation in hospital. Simple suturing of
      the ulcer was found to be inconsistent in effectively maintaining hemostasis.
      Surgical excision of the ulcer with primary closure, vein patching of the
      fistula, or end-end anastomosis were equally effective in definitively correcting
      the problem. CONCLUSIONS: The ulcerated autologous dialysis fistula is a life
      threatening lesion and requires prompt surgical intervention to reduce mortality.
      The frequency of this problem appears to be increasing. Simple suturing of the
      ulcers was not consistently effective in remedying the problem and should be
      utilized as a temporizing measure until surgical correction can be undertaken.
      Fistulas can be uniformly salvaged with surgical intervention enabling
      uninterrupted dialysis treatments.

PMID- 21725947
TI  - Power injection of iodinated intravenous contrast material through acute and
      chronic hemodialysis catheters.
AB  - PURPOSE: End-stage renal disease patients with hemodialysis catheters in need of
      contrast enhanced imaging studies often have limited peripheral venous access. In
      this study we aimed to determine pressures generated in hemodialysis catheters
      during power injection of computed tomography (CT) contrast media. METHODS: Three
      different chronic hemodialysis catheters and two acute hemodialysis catheters
      were included in this study. All catheters were evaluated in vitro. A total
      volume of 120 cc of CT contrast material was injected at rate of 10 cc/s using a
      power injector. The catheters were connected to the power injector using a
      standard connecting tubing. Pressures were simultaneously measured in the power
      injector as well as in the hemodialysis catheters. RESULTS: The maximal measured
      pressures during injection in the power injector averaged 338 PSI (SD +/- 8.7
      PSI). The maximal measured pressure in the dialysis catheters ranged between 9.17
      and 21.2 PSI. Pressures averaged 14.02 PSI (SD +/- 3.34 PSI). The average
      pressure in the power injector was over 23 times higher than the pressure
      recorded at the hemodialysis catheter. None of the catheters ruptured or deformed
      during testing. CONCLUSIONS: Pressures measured in hemodialysis catheters during
      power injection are lower than currently believed and markedly lower than the
      pressures recorded in the power injector. Standard hemodialysis catheters are
      likely to be amenable to power contrast injection in hemodialysis patients who
      have limited venous access. In vivo studies are necessary to confirm these
      findings.

PMID- 21725948
TI  - A comparison between blood flow outcomes of tunneled external jugular and
      internal jugular hemodialysis catheters.
AB  - PURPOSE: The right internal jugular (RIJ) vein is preferred for placement of long
      term venous catheters (CVC) for hemodialysis (HD). Use of left IJ vein
      potentially depletes the access site for arteriovenous fistula (AVF) or
      arteriovenous graft (AVF) placement because of the high rates of central venous
      stenosis. The right external jugular (EJ) vein is a viable alternative to the
      LIJ. The purpose of this study is to compare blood flow outcomes in a series of
      percutaneously placed external jugular (EJ), LIJ and RIJ HD catheters. METHODS:
      Using a prospectively collected database, we identified 46 hemodialysis patients
      who received a tunneled catheter during a 4-year period. Blood flow outcomes of
      RIJ, LIJ, and EJ catheters that were date-matched over the study period were
      compared. Using ANOVA, the blood flow outcomes of the 3 tunneled catheter
      techniques at 30-d and 90-d were compared. RESULTS: The 90-d blood flow outcomes
      of the 3 groups did not differ significantly. The 30-d blood flow was found to be
      348.5+/- 56.62, 341+/- 22.42, and 365.7+/- 71.76 mL/min for RIJ, LIJ, and EJ
      respectively (P<.05). Using multiple regression analysis, no covariates (age,
      sex, race, diabetes) were found to be associated with blood flow outcomes at 30-d
      or 90-d. No identifiable factors were found to be associated with the difference
      in blood flow between 30-d and 90-d either. CONCLUSIONS: EJ blood flow outcomes
      at 30-d and 90-d were comparable to both LIJ and RIJ historic data. Further
      prospective investigation is required to define the role of EJ CVC placement as
      another potential long-term access modality.

PMID- 21725949
TI  - Prehospital peripheral venous catheters: a prospective study of patient
      complications.
AB  - PURPOSE: To investigate prehospital peripheral venous catheters (PVCs) in
      relation to the frequency of thrombophlebitis. METHOD: Data in this prospective
      study were collated using three types of data source: a study-specific
      questionnaire, a PVC observation instrument (PVC assess), and electronic patient
      records. The questionnaire was distributed to ambulance crews who had inserted a
      PVC before bringing the patient to an emergency department at a level one trauma
      centre in Sweden during 10 weeks in 2008-2009. Patients admitted to hospital ward
      were followed-up daily by registered nurses using the PVC assess until the PVC
      was removed. Patient record data were collected by means of auditing. RESULTS: Of
      the 83 patients available for follow-up, 45 (54%) developed thrombophlebitis.
      Quick PVC removal was performed in 32 (71%) of these patients while 13 (29%) PVCs
      were left in situ for 1-8 days. No association was found between the occurrence
      of thrombophlebitis and potential risk factors. CONCLUSIONS: Although
      thrombophlebitis frequently occurred in PVCs inserted in a prehospital setting,
      early removal of the device with complication was common. Further studies are
      warranted to identify the optimal in situ time for PVCs inserted by prehospital
      emergency teams.

PMID- 21725950
TI  - Computational fluid dynamics simulation of a-v fistulas: from MRI and ultrasound
      scans to numeric evaluation of hemodynamics.
AB  - PURPOSE: A-v anastomosis entails dramatic changes in hemodynamic conditions,
      which may lead to major alterations to the vessels involved; primarily
      dilatations and devastating stenoses. Wall shear stress is thought to play a key
      role in the remodeling of the vessels exposed to abnormal levels and oscillating
      wall shear stress. In this study we sought to develop a framework suitable for
      thorough in vivo analyses of wall shear stress and vessel morphology of a-v
      fistulas in patients. METHODS: Using ultrasound and magnetic resonance imaging
      (MRI) transverse image stacks from six patient a-v fistulas were obtained. From
      the image stacks three-dimensional geometries of the patient fistulas were
      created using dedicated segmentation software. Geometries of three a-v fistulas
      were imported into finite element software in order to perform fluid flow
      simulations of blood flows and frictional forces on the vessel walls in the a-v
      fistulas. Boundary conditions for the simulations were obtained using both a MRI
      phase contrast and an ultrasound Doppler technique. RESULTS: The segmentation of
      the six fistulas of very different age and morphology (two end-to-side and four
      side-to-side) showed the ability of the approach to create geometries of various
      fistula morphologies. Simulations of the three fistulas showed an instant picture
      of the present status of the exposure to different levels of wall shear stress
      and the morphological status in the vessel remodeling process. CONCLUSION: The
      study demonstrated the capability of the CFD framework to analyze patient a-v
      fistulas on a regular basis using both MRI and ultrasound-based approaches.

PMID- 21725951
TI  - Challenging lower extremity dialysis access: long-term use of a leg AV-fistula.

PMID- 21725952
TI  - Extraction of a 17-year-old pacing lead chronically dislocated into the liver
      vein.

PMID- 21725953
TI  - Central venous access port devices - a pictorial review of common complications
      from the interventional radiology perspective.
AB  - Portacaths are tunnelled and totally implanted central venous access port devices
      (CVAPD). They are commonly used for intravenous antibiotic delivery in patients
      with cystic fibrosis. More recently, they are being used in oncology to deliver
      chemotherapy and apheresis. It is therefore important to be aware of portacath
      associated complications and their imaging features. This pictorial review
      illustrates and discusses common complications associated with Portacath devices.

PMID- 21725954
TI  - A case of bleeding access.

PMID- 21725955
TI  - Catheter-based flow measurements in hemodialysis fistulas - bench testing and
      clinical performance.
AB  - PURPOSE: The purpose of this study was to perform bench and clinical testing of a
      catheter-based intravascular system capable of measuring blood flow in
      hemodialysis vascular accesses during endovascular procedures. METHODS: We tested
      the Transonic ReoCath Flow Catheter System which uses the thermodilution method.
      A simulated vascular access model was constructed for the bench test. In total,
      1960 measurements were conducted and the results were used to determine the
      accuracy and precision of the catheters, the effects of external factors (e.g.,
      catheter placement, injection duration), and to test for systematic bias. In the
      clinical study, two interventional radiologists conducted a total of 250
      measurements in 14 patients with arteriovenous fistulas to determine clinical
      precision and enable testing for bias between measurers. RESULTS: Accuracy was
      excellent for both catheters with a high level of agreement between results from
      the ReoCath Flow Catheter System and the reference flowmeter. Clinical precision,
      expressed as the mean coefficient of variation, was 5.9% and 4.7% for the
      antegrade and retrograde catheters, respectively. Flow measurements were
      significantly affected by the distance between a stenosis and the tip of a
      retrograde catheter with the effect being proportional to the degree of stenosis.
      There was no systematic bias between measurers. CONCLUSIONS: The Reocath Flow
      Catheter System was found to be accurate and precise. Reliable results require
      careful attention to catheter placement. Blood flow measurements provide unique
      information on the hemodynamic status of a vascular access and have the potential
      to optimize results of interventions.

PMID- 21725956
TI  - The endovenous revolution.

PMID- 21725957
TI  - Randomized clinical trial comparing endovenous laser ablation, radiofrequency
      ablation, foam sclerotherapy and surgical stripping for great saphenous varicose
      veins.
AB  - BACKGROUND: This randomized trial compared four treatments for varicose great
      saphenous veins (GSVs). METHODS: Five hundred consecutive patients (580 legs)
      with GSV reflux were randomized to endovenous laser ablation (980 and 1470 nm,
      bare fibre), radiofrequency ablation, ultrasound-guided foam sclerotherapy or
      surgical stripping using tumescent local anaesthesia with light sedation.
      Miniphlebectomies were also performed. The patients were examined with duplex
      imaging before surgery, and after 3 days, 1 month and 1 year. RESULTS: At 1 year,
      seven (5.8 per cent), six (4.8 per cent), 20 (16.3 per cent) and four (4.8 per
      cent) of the GSVs were patent and refluxing in the laser, radiofrequency, foam
      and stripping groups respectively (P < 0.001). One patient developed a pulmonary
      embolus after foam sclerotherapy and one a deep vein thrombosis after surgical
      stripping. No other major complications were recorded. The mean(s.d.)
      postintervention pain scores (scale 0-10) were 2.58(2.41), 1.21(1.72), 1.60(2.04)
      and 2.25(2.23) respectively (P < 0.001). The median (range) time to return to
      normal function was 2 (0-25), 1 (0-30), 1 (0-30) and 4 (0-30) days respectively
      (P < 0.001). The time off work, corrected for weekends, was 3.6 (0-46), 2.9 (0
      14), 2.9 (0-33) and 4.3 (0-42) days respectively (P < 0.001). Disease-specific
      quality-of-life and Short Form 36 (SF-36((r))) scores had improved in all groups
      by 1-year follow-up. In the SF-36((r)) domains bodily pain and physical
      functioning, the radiofrequency and foam groups performed better in the short
      term than the others. CONCLUSION: All treatments were efficacious. The technical
      failure rate was highest after foam sclerotherapy, but both radiofrequency
      ablation and foam were associated with a faster recovery and less postoperative
      pain than endovenous laser ablation and stripping.

PMID- 21725958
TI  - Randomized clinical trial comparing endovenous laser ablation, radiofrequency
      ablation, foam sclerotherapy and surgical stripping for great saphenous varicose
      veins (Br J Surg 2011; 98: 1079-1087).

PMID- 21725959
TI  - Development of a composite endpoint for randomized controlled trials in liver
      surgery (Br J Surg 2011; 98: 1138-1145).

PMID- 21725960
TI  - Effect of injury on S1 dorsal root ganglia in an experimental model of
      neuropathic faecal incontinence (Br J Surg 2011; 98: 1155-1159) and Sacral nerve
      stimulation increases activation of the primary somatosensory cortex by anal
      canal stimulation in an experimental model (Br J Surg 2011; 98: 1160-1169).

PMID- 21725961
TI  - Randomized clinical trial of combined preincisional infiltration and
      intraperitoneal instillation of levobupivacaine for postoperative pain after
      laparoscopic cholecystectomy (Br J Surg 2011; 98: 784-789).

PMID- 21725963
TI  - Multicentre evaluation of intraoperative molecular analysis of sentinel lymph
      nodes in breast carcinoma (Br J Surg 2011; 98: 527-535).

PMID- 21725965
TI  - Laparoscopic resection of advanced colorectal cancer (Br J Surg 2011; 98: 427
      430).

PMID- 21725968
TI  - Cost-effectiveness of screening for abdominal aortic aneurysm in the Netherlands
      and Norway.
AB  - BACKGROUND: The aim of this study was to determine the cost-effectiveness of
      ultrasound screening for abdominal aortic aneurysm (AAA) in men aged 65 years,
      for both the Netherlands and Norway. METHODS: A Markov model was developed to
      simulate life expectancy, quality-adjusted life-years, net health benefits,
      lifetime costs and incremental cost-effectiveness ratios for both screening and
      no screening for AAA. The best available evidence was retrieved from the
      literature and combined with primary data from the two countries separately, and
      analysed from a national perspective. A threshold willingness-to-pay (WTP) of
      ?20,000 and ?62,500 was used for data from the Netherlands and Norway
      respectively. RESULTS: The additional costs of the screening strategy compared
      with no screening were ?421 (95 per cent confidence interval 33 to 806) per
      person in the Netherlands, and the additional life-years were 0.097 (-0.180 to
      0.365), representing ?4340 per life-year. For Norway, the values were ?562 (59 to
      1078), 0.057 (-0.135 to 0.253) life-years and ?9860 per life-year respectively.
      In Norway the results were sensitive to a decrease in the prevalence of AAA in 65
      year-old men to 1 per cent, or lower. Probabilistic sensitivity analyses
      indicated that AAA screening has a 70 per cent probability of being cost
      effective in the Netherlands with a WTP threshold of ?20,000, and 70 per cent in
      Norway with a threshold of ?62,500. CONCLUSION: Using this model, screening for
      AAA in 65-year-old men would be highly cost-effective in both the Netherlands and
      Norway.

PMID- 21725969
TI  - Role of pressure and pancreatic reflux in the aetiology of choledochal
      malformation.
AB  - BACKGROUND: The aetiology of choledochal malformation is not known. Babbitt's
      hypothesis remains a popular concept, and assumes that activated pancreatic juice
      refluxes through the common pancreatobiliary channel causing mural damage and
      subsequent biliary dilatation. This hypothesis was tested clinically by
      evaluating the relationship between epithelial histology, choledochal pressure
      and degree of pancreatic reflux. METHODS: Children with choledochal malformation
      (cystic, type 1c; fusiform, type 1f; both intrahepatic and extrahepatic
      dilatation, type 4) operated on between January 1999 and October 2009 were
      identified. Where practical, choledochal pressure was measured on entry to the
      abdominal cavity, by puncture of the common bile duct, and bile was sampled for
      amylase content. Archival bile duct sections were scored using a semiquantitative
      epithelial lining/mural score (ELMS). RESULTS: A total of 90 children with
      choledochal malformations were operated on during the study interval. Histology
      was available for 73 children (median age 2.9 (interquartile range 1.3-7.9)
      years), 29 with type 1c, 31 with type 1f and 13 with type 4 malformations. There
      was a significant stepwise increase in pressure with choledochal morphology
      (median pressure 13, 17 and 20 mmHg for types 1f, 1c and 4 respectively; P =
      0.037). There was an inverse relationship between choledochal pressure and bile
      amylase activity (r(s) = - 0.45, P < 0.001). High ELMS values were associated
      with higher choledochal pressure (P = 0.057) and low bile amylase activity (P =
      0.002). CONCLUSION: High choledochal pressure (not bile amylase) was associated
      with more severe histopathological changes and choledochal morphology. These
      findings suggest that distal bile duct obstruction (and therefore high
      intraluminal pressure) contributes more to the key features of choledochal
      malformation than does pancreatic reflux.

PMID- 21725970
TI  - Prediction, prevention and management of postresection liver failure.
AB  - BACKGROUND: Postresection liver failure (PLF) is the major cause of death
      following liver resection. However, there is no unified definition, the
      pathophysiology is understood poorly and there are few controlled trials to
      optimize its management. The aim of this review article is to present strategies
      to predict, prevent and manage PLF. METHODS: The Web of Science, MEDLINE, PubMed,
      Google Scholar and Cochrane Library databases were searched for studies using the
      terms 'liver resection', 'partial hepatectomy', 'liver dysfunction' and 'liver
      failure' for relevant studies from the 15 years preceding May 2011. Key papers
      published more than 15 years ago were included if more recent data were not
      available. Papers published in languages other than English were excluded.
      RESULTS: The incidence of PLF ranges from 0 to 13 per cent. The absence of a
      unified definition prevents direct comparison between studies. The major risk
      factors are the extent of resection and the presence of underlying parenchymal
      disease. Small-for-size syndrome, sepsis and ischaemia-reperfusion injury are key
      mechanisms in the pathophysiology of PLF. Jaundice is the most sensitive
      predictor of outcome. An evidence-based approach to the prevention and management
      of PLF is presented. CONCLUSION: PLF is the major cause of morbidity and
      mortality after liver resection. There is a need for a unified definition and
      improved strategies to treat it.

PMID- 21725971
TI  - The influence of mTOR on T helper cell differentiation and dendritic cell
      function.
AB  - The mammalian target of rapamycin (mTOR) integrates signalling responses to
      growth factors and nutrients. The macrolide rapamycin inhibits mTOR function and
      has been used extensively to demonstrate a critical role for mTOR in immune
      responses. This mini-review summarizes recent evidence demonstrating an integral
      role for mTOR in the differentiation of T helper cell subsets and the
      development, maturation and antigen-presenting capacity of DCs in both mice and
      humans.

PMID- 21725972
TI  - Spermatocytic seminoma: toward further understanding of pathogenesis.
AB  - Human germ cell tumours comprise a heterogeneous group of neoplasms which, based
      on pathobiological, genetic and clinical characteristics, can be subdivided into
      different entities. One of these subgroups relates to the so-called spermatocytic
      seminomas, benign tumours only found in the testis, preferentially in elderly
      men. Various developmental models for this type of germ cell tumour have been
      proposed and it is clear that spermatocytic seminoma has a pathogenesis
      independent from that of seminoma. A recent study examining expression of
      spermatogonial markers shows that spermatocytic seminomas are a heterogeneous
      group of tumours, with a supposed difference in origin, ie the majority from
      A(pale) or B spermatogonia, and a minority from A(dark) spermatogonia. However,
      this does not exclude an earlier cell of origin, possibly explaining the unique
      properties of this type of human germ cell tumour, with various counterparts in
      animals.

PMID- 21725973
TI  - Epigallocatechin-3-gallate induces growth inhibition and apoptosis of human
      anaplastic thyroid carcinoma cells through suppression of EGFR/ERK pathway and
      cyclin B1/CDK1 complex.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most lethal cancers
      because of its aggressiveness and the lack of efficacious therapy.
      Epigallocatechin-3-gallate (EGCG), a major catechin in green tea, was shown to
      possess remarkable therapeutic potential against various types of human cancer
      cells in in vitro and in vivo models. The aim of this study was to investigate
      the effect of EGCG on the proliferation and apoptosis of ARO cells--human ATC
      cells. STUDY DESIGN: Experimental study. METHODS: Human ATC cell line, ARO, was
      treated with EGCG. Cell viability was assessed by MTT assay. Inhibition of
      EGFR/MAPK pathway and cell cycle-related proteins by EGCG were measured by
      Western blot analysis. In addition, cell cycle analysis was measured by flow
      cytometry. RESULTS: EGCG treatment inhibited the growth of ARO cells in a dose
      dependent manner. Furthermore, EGCG suppressed phosphorylation of EGFR, ERK1/2,
      JNK, and p38. These changes were associated with increased p21 and reduced cyclin
      B1/CDK1 expression. In addition, EGCG treatment increased the accumulation of sub
      G1 cell, activated caspase-3 and cleaved PARP. CONCLUSIONS: Taken together, EGCG
      inhibits cell proliferation and induces apoptosis via suppression of the EGFR/ERK
      pathway and cyclin B1/CDK1 complex in ATC cells.

PMID- 21725974
TI  - Genome-wide transcriptional profiling analysis of all trans retinoic acid-treated
      tongue carcinoma SCC-9 cells.
AB  - BACKGROUND: All trans retinoic acid (ATRA) is used as standard of care in
      promyelocytic leukemia. Not much is known about the gene expression profile in
      ATRA-treated tongue cancer cells. We performed a genome-wide transcriptional
      profiling of ATRA-treated tongue cancer cells to understand the pathways that
      mediate ATRA action in tongue cancer. METHODS: We measured the effects of ATRA on
      the proliferation of SCC-9 human tongue carcinoma cells. The differential gene
      expression profile was measured by microarray analysis of untreated and ATRA
      treated cells and expression of key genes was validated by real-time RT-PCR.
      RESULTS: ATRA treatment (24 and 48 hr) significantly inhibited SCC-9 cell
      proliferation in a dose-dependent manner. SCC-9 cells treated for 48 hr with ATRA
      showed upregulation of 276 genes, including ANGPTL4, GDF15, ICAM1 and TUSC4, and
      downregulation of 43 genes, including CXCL10. Validation by real-time PCR showed
      a significant upregulation of intracellular adhesion molecule 1 (ICAM1) and
      downregulation of CXCL10 and IL32. CONCLUSIONS: ATRA had an anti-tumor effect in
      tongue cancer cells. This effect is likely mediated via upregulation of ICAM1 and
      downregulation of CXCL10 and IL32.

PMID- 21725975
TI  - Antifreeze glycoprotein agents: structural requirements for activity.
AB  - Antifreeze glycoproteins (AFGPs) are considered to be the most efficient means to
      reduce ice damage to cell tissues since they are able to inhibit growth and
      crystallization of ice. The key element of antifreeze proteins is to act in a non
      colligative manner which allows them to function at concentrations 300-500 times
      lowers than other dissolved solutes. During the past decade, AFGPs have
      demonstrated tremendous potential for many pharmaceutical and food applications.
      Presently, the only route to obtain AFGPs involves the time consuming and
      expensive process of isolation and purification from deep-sea polar fishes.
      Unfortunately, it is not amenable to mass production and commercial applications.
      The lack of understanding of the mechanism through which the AFGPs inhibit ice
      growth has also hampered the realization of industrial and biotechnological
      applications. Here we report the structural motifs that are essential for
      antifreeze activity of AFGPs, and propose a unified mechanism based on both
      recent studies of short alanine peptides and structure activity relationship of
      synthesized AFGPs.

PMID- 21725976
TI  - Metastases to the pancreas: the experience of a high volume center and a review
      of the literature.
AB  - BACKGROUND: Metastasis to the pancreas (PM) is uncommon. Several types of cancers
      were reported to metastasize to the pancreas. Surgery is advocated in selected
      patients when technically feasible and if the patient can be rendered disease
      free. METHODS: A retrospective review of PM patients at the University of
      Cincinnati Pancreas Database was performed over a 7-year time period. RESULTS:
      Twenty patients with a median age of 62.5 years were identified. Fifteen patients
      (75%) were males and (50%) presented with abdominal pain. Nine patients (45.0%)
      were offered surgical resection, distal pancreatectomy was the most common
      procedure (n = 4, 44.4%). The commonest pathology was RCC (60%), followed by lung
      (20%), colon (15%), and breast (5%). Median disease free interval (DFI) was 96
      months for RCC, 7 months for other pathologies. Median survival was 19 months for
      RCC, 8.5 months for other pathologies. Based on DFI, short DFI patients (<=12
      months) had worse prognosis (2-year survival of 40%), as opposed to (2-year
      survival of 80%) in longer DFI patients (P = 0.01). RCC patients with a DFI
      longer than 94 months had a better survival (P = 0.01). Survival of resected PM
      tended to be longer than non-resected PM (P = 0.11). CONCLUSIONS: PM from RCC
      carries a consistently favorable prognosis compared to other pathologies.
      Surgical resection of PM is a safe and viable option, and, in selected patients,
      may improve survival. However, a period of expectant management in patients with
      short DFI may be considered.

PMID- 21725977
TI  - Evaluation of genetic markers for identifying isolates of the species of the
      genus Fusarium.
AB  - BACKGROUND: Members of the genus Fusarium are well known as one of the most
      important plant pathogens causing food spoilage and loss worldwide. Moreover,
      they are associated with human and animal diseases through contaminated foods
      because they produce mycotoxins. To control fungal hazards of plants, animals and
      humans, there is a need for a rapid, easy and accurate identification system of
      Fusarium isolates with molecular methods. RESULTS: To specify genes appropriate
      for identifying isolates of various Fusarium species, we sequenced the 18S rRNA
      gene (rDNA), internal transcribed spacer region 1, 5.8S rDNA, 28S rDNA, beta
      tubulin gene (beta-tub), and aminoadipate reductase gene (lys2), and subsequently
      calculated the nucleotide sequence homology with pair-wise comparison of all
      tested strains and inferred the ratio of the nucleotide substitution rates of
      each gene. Inter-species nucleotide sequence homology of beta-tub and lys2 ranged
      from 83.5 to 99.4% and 56.5 to 99.0%, respectively. The result indicated that
      sequence homologies of these genes against reference sequences in a database have
      a high possibility of identifying unknown Fusarium isolates when it is more than
      99.0%, because these genes had no inter-species pair-wise combinations that had
      100% homologies. Other markers often showed 100% homology in inter-species pair
      wise combinations. The nucleotide substitution rate of lys2 was the highest among
      the six genes. CONCLUSION: The lys2 is the most appropriate genetic marker with
      high resolution for identifying isolates of the genus Fusarium among the six
      genes we examined in this study.

PMID- 21725978
TI  - The potential reuse of soybean husk as feedstock of Eudrilus eugeniae in
      vermicomposting.
AB  - BACKGROUND: Soybean (Glycine max L.) is one the most commonly consumed legumes
      worldwide, with 200 million metric tons produced per year. However, the inedible
      soy husk would usually be removed during the process and the continuous
      generation of soybean husk may represent a major disposal problem for soybean
      processing industries. Thus, the main aim of the present study was to investigate
      the possibility to convert soybean husk (S) amended with market-rejected papaya
      (P) into vermicompost using Eudrilus eugeniae. RESULTS: Soybean husk was mixed
      with market-rejected papaya in different ratios to produce five different
      treatments (1P:1S, 2P:1S, 1P:2S, S only and P only) for laboratory screening of
      solid wastes. Generally, the application of E. eugeniae permitted a significant
      increase in Ca (42.3-91.6%), K (93.8-235%), Mg (25.4-84.6%) and P (37.1-129%) but
      a decrease in the C:N ratio (21.4-52.8%) after 9 weeks of vermicomposting. Among
      all the treatments investigated, soybean husk which was mixed with an equal
      amount of market-rejected papaya (1P:1S) showed superior quality vermicompost.
      Waste mixtures also encouraged the growth of E. eugeniae except the treatments
      with soybean husk alone as well as soybean husk which was mixed with market
      rejected papaya in 1P:2S ratio. CONCLUSION: Vermicomposting could be used as an
      efficient technology to convert soybean husk into nutrient-rich organic
      fertiliser if it was mixed with market-rejected papaya in appropriate ratio.

PMID- 21725979
TI  - Hydrolysable tannins of tropical almond show antifibrotic effects in TGF-beta1
      induced hepatic stellate cells.
AB  - BACKGROUND: Persistent activation of hepatic stellate cells (HSC-T6) has been
      known to cause liver fibrosis. In this study, our objective was to investigate
      the effects of chebulagic acid and chebulinic acid, two hydrolysable tannins of
      tropical almond (Terminalia chebula) fruits, on collagen synthesis and signal
      transduction in transforming growth factor-beta1-stimulated HSC-T6 cells. The
      expression of Smad2, Smad3, Smad4, collagen I(alpha1)/III, and plasminogen
      activator inhibitor 1 (PAI-1) mRNAs was determined by reverse-transcription
      polymerase chain reaction and their protein levels were assessed by western
      blotting. RESULTS: Results showed that chebulagic acid and chebulinic acid at 20
      umol L(-1) exhibited cytotoxic and anti-proliferative effects on HSC-T6 cells.
      They also significantly decreased the expression of Smd2, Smad3 and Smad4, and
      the synthesis of collagen, procollagen I (alpha1) and III, as well as suppressing
      the activation of PAI-1; these events consequently facilitated the resolution of
      fibrosis. CONCLUSION: These results indicate that both chebulagic acid and
      chebulinic acid possess antifibrotic activity, and their mechanism of action
      could be through the inhibition of the Smad pathway.

PMID- 21725980
TI  - Aroma volatile compositions of high- and low-aromatic guava varieties.
AB  - BACKGROUND: The traditional guava variety cultivated in Israel, 'Ben Dov', emits
      a very strong odour, whereas some newly bred varieties have a mild odour. In this
      study the aroma profile composition of the high-aromatic 'Ben Dov' variety was
      compared with those of four new low-aromatic varieties. RESULTS: Overall, using
      gas chromatography/mass spectrometry, a total of 30 aroma volatiles were detected
      in fresh ripe guava fruit: 15 of them were specifically detected only in the high
      aromatic 'Ben Dov' variety, 13 were detected in both the high- and low-aromatic
      varieties and two were detected only in the new low-aromatic varieties.
      Interestingly, 11 out of the 15 volatiles specifically detected in 'Ben Dov' were
      esters that contribute sweet, tropical and fruity notes. In contrast, ten out of
      13 detected terpenes and two detected aldehydes, contributing green, spicy,
      herbal and woody notes, were common to both the high- and low-aromatic varieties.
      CONCLUSION: Based on these findings, it is concluded that accumulation of esters
      is the main reason why the traditional 'Ben Dov' guava variety emits such a
      strong tropical fruity odour. In contrast, the newly bred low-aromatic guava
      varieties did not synthesise esters at all and thus lacked fruity aromatic notes.
      Overall, the results of this study point out the important role of esters in
      forming tropical fruity guava odours.

PMID- 21725981
TI  - Effect of kafirin protein coating on sensory quality and shelf-life of 'Packham's
      Triumph' pears during ripening.
AB  - BACKGROUND: Pears are exported in large quantities from South Africa, resulting
      in large revenues. Minimisation of quality losses once the fruit has reached the
      export destination is as important as following strict export and distribution
      protocols. Kafirin can form edible films. In this study an edible coating made
      from 20 g kg(-1) kafirin coating solution was applied as a postharvest treatment
      to retard quality deterioration of 'Packham's Triumph' pears during storage at
      the typical ripening temperature (20  degrees C). Changes in physicochemical and
      sensory quality were monitored over a period of 24 days. RESULTS: The kafirin
      coating was unable to retard the onset of ripening but decreased the respiration
      rate and retarded the progression of senescence. However, moisture loss was
      exacerbated in the kafirin-coated fruit during ripening at 20  degrees C,
      especially towards the end of the shelf-life. CONCLUSION: The kafirin coating
      extended the eat-ripe quality of the pears by 1-2 weeks. However, the appearance
      of the fruit was unacceptable after 14 days of storage in terms of wrinkled skin.
      Further work is needed to improve the water barrier properties of the kafirin
      coating by incorporating a wax or triglyceride into the coating formulation or
      more simply by applying a kafirin coating to waxed fruit.

PMID- 21725982
TI  - Simultaneous detection of Ponceat 4R and tartrazine in food using adsorptive
      stripping voltammetry on an acetylene black nanoparticle-modified electrode.
AB  - BACKGROUND: Ponceau 4R and tartrazine have been widely used in foodstuffs.
      However, they are pathogenic if they are excessively consumed. Therefore, the
      detection of Ponceat 4R and tartrazine is quite important. RESULTS: A sensitive
      and rapid electrochemical method was developed for the simultaneous detection of
      Ponceat 4R and tartrazine using anodic adsorptive stripping voltammetry and based
      on the strong enhancement effect of acetylene black nanoparticle. For Ponceat 4R,
      the linear range was from 0.05 to 4 mg kg(-1) , and the limit of detection was
      0.03 mg kg(-1) . For tartrazine, the linear range was from 0.15 to 18 mg kg(-1) ,
      and the limit of detection was 0.1 mg kg(-1) . The relative standard deviation
      was 3.8% and 4.7% for 10 successive measurements of 1 mg kg(-1) Ponceau 4R and
      tartrazine. The method was used to determine Ponceat 4R and tartrazine in soft
      drinks, and recovery was in the range of 92.4-104.8%. CONCLUSION: At the
      acetylene black nanoparticle-modified electrode, the oxidation current signal of
      Ponceau 4R and tartrazine greatly increase. This new method is sensitive, rapid,
      simple and feasible.

PMID- 21725983
TI  - Rocket salad (Diplotaxis and Eruca spp.) sensory analysis and relation with
      glucosinolate and phenolic content.
AB  - BACKGROUND: Salad crops of the Brassicaceae family, such as Diplotaxis tenuifolia
      and Eruca vesicaria, commonly referred to as 'rocket salads', have attracted
      considerable interest as culinary vegetables because of their strong flavour and
      their content of putative health-promoting compounds. Among such compounds,
      glucosinolates and phenolics are well-known phytochemicals with an important role
      also in determining the characteristic flavour of these species. In this study,
      to identify potentially high-value rocket salads, 37 cultivated types were
      examined for sensory characters and their relations with glucosinolate and
      phenolic contents, which ranged from 0.76 to 3.03 g kg(-1) dry weight (DW) and
      from 4.68 to 31.39 g kg(-1) DW, respectively. RESULTS: The perception of bitter
      taste was significantly affected by specific glucosinolates, namely
      progoitrin/epiprogoitrin and dimeric glucosativin. Aroma intensity was negatively
      related to glucoalyssin content, whereas pungency was significantly related to
      total glucosinolate content. Kaempferol-3-(2-sinapoyl-glucoside)-4'-glucoside was
      positively and significantly related to all flavour trait perceptions. Aroma
      intensity, pungency, crunchiness and juiciness were positively related to typical
      rocket salad flavour perception through a prominent direct effect. CONCLUSION:
      Aroma intensity, pungency, crunchiness and juiciness were strong determinants of
      overall rocket salad flavour perception. Visual traits also characterised sensory
      components. Bitterness, usually considered a negative flavour trait, was
      moderately perceived in the examined material, without negatively affecting
      typical flavour perception. In the range of the examined material, glucosinolate
      content did not contrast with typical flavour, demonstrating that good taste and
      putative health-promoting properties may coexist.

PMID- 21725984
TI  - Extruded aquafeeds containing distillers dried grains with solubles: effects on
      extrudate properties and processing behaviour.
AB  - BACKGROUND: The tremendous supply and low cost of distillers dried grains with
      solubles (DDGS) make it an attractive feedstuff for aquaculture diets. Also,
      several studies have shown that DDGS can be successfully fed to various finfish.
      The objective of this study was to evaluate the effects of inclusion rate of DDGS
      (0, 250, 500 g kg(-1) ), feed moisture content (350, 450 g kg(-1) ) and die
      opening area (die A = 18.85 mm(2) , die B = 3988.45 mm(2) ) on the properties of
      the extrudates and on processing behaviour using a single-screw extruder.
      RESULTS: Increasing the inclusion rate of DDGS resulted in extrudates with lower
      unit density, bulk density, expansion ratio, water solubility index and
      brightness (Hunter L) but higher redness (Hunter a) and yellowness (Hunter b).
      The increase in moisture content affected the extrudate properties in different
      ways: it increased bulk density, Hunter L, Hunter b and mass flow rate, whereas
      specific mechanical energy decreased at high moisture content. Increasing the die
      opening area primarily decreased expansion ratio of extrudates, power consumption
      and barrel temperatures but increased mass flow rate. CONCLUSION: Extrudates from
      all treatments exhibited high durability and floatability, and less energy was
      required to produce extrudates when DDGS was used compared with soybean meal
      based diets. The aquaculture industry can use this information to develop high
      quality feeds at low cost.

PMID- 21725985
TI  - Are there differences in the catalytic activity per unit enzyme of recombinantly
      expressed and human liver microsomal cytochrome P450 2C9? A systematic
      investigation into inter-system extrapolation factors.
AB  - The 'relative activity factor' (RAF) compares the activity per unit of microsomal
      protein in recombinantly expressed cytochrome P450 enzymes (rhCYP) and human
      liver without separating the potential sources of variation (i.e. abundance of
      enzyme per mg of protein or variation of activity per unit enzyme). The
      dimensionless 'inter-system extrapolation factor' (ISEF) dissects differences in
      activity from those in CYP abundance. Detailed protocols for the determination of
      this scalar, which is used in population in vitro-in vivo extrapolation (IVIVE),
      are currently lacking. The present study determined an ISEF for CYP2C9 and, for
      the first time, systematically evaluated the effects of probe substrate,
      cytochrome b5 and methods for assessing the intrinsic clearance (CL(int) ).
      Values of ISEF for S-warfarin, tolbutamide and diclofenac were 0.75 +/- 0.18,
      0.57 +/- 0.07 and 0.37 +/- 0.07, respectively, using CL(int) values derived from
      the kinetic values V(max) and K(m) of metabolite formation in rhCYP2C9 +
      reductase + b5 BD SupersomesTM. The ISEF values obtained using rhCYP2C9 +
      reductase BD SupersomesTM were more variable, with values of 7.16 +/- 1.25, 0.89
      +/- 0.52 and 0.50 +/- 0.05 for S-warfarin, tolbutamide and diclofenac,
      respectively. Although the ISEF values obtained from rhCYP2C9 + reductase + b5
      for the three probe substrates were statistically different (p < 0.001), the use
      of the mean value of 0.54 resulted in predicted oral clearance values for all
      three substrates within 1.4 fold of the observed literature values. For
      consistency in the relative activity across substrates, use of a b5 expressing
      recombinant system, with the intrinsic clearance calculated from full kinetic
      data is recommended for generation of the CYP2C9 ISEF. Furthermore, as ISEFs have
      been found to be sensitive to differences in accessory proteins, rhCYP system
      specific ISEFs are recommended.

PMID- 21725986
TI  - Protective effects of salecan against carbon tetrachloride-induced acute liver
      injury in mice.
AB  - Carbon tetrachloride (CCl4) is a well-established model for screening hepato
      protective drugs. The aim of the present study was to evaluate the potential
      protective effects of a novel soluble beta-glucan salecan on acute liver injury
      induced by CCl4 in mice and to further explore the underlying mechanisms. Mice
      were given salecan (40 mg kg-1) or phosphate-buffered saline for 3 days prior to
      treatment with a single intraperitoneal dose of CCl4 (1 ml kg-1 body weight).
      Animals were sacrificed at 0, 12, 24, 48, 72 and 96 h post-injection of CCl4.
      Serum liver enzyme levels, histology, lipid peroxidation, glutathione (GSH)
      content, expression of antioxidant enzymes and hepatocyte proliferation were
      subsequently evaluated. The serum levels of hepatic enzyme markers were markedly
      reduced in the salecan pretreatment group compared with the control group.
      Histopathological examination of the livers revealed that hepatocellular
      degeneration and necrosis were significantly attenuated at an early stage during
      CCl4 intoxication and liver recovery was markedly accelerated at a later stage in
      salecan pre-administered mice. Furthermore, salecan administration remarkably
      alleviated lipid peroxidation and restored GSH depletion. Meanwhile, the
      expression of antioxidant genes was significantly elevated in the salecan-treated
      group. Interestingly, the administration of salecan remarkably enhanced
      hepatocyte proliferation in the recovery phase after CCl4 injection. Taken
      together, these results demonstrated that salecan exhibits a protective action on
      acute hepatic injury induced by CCl4 through attenuating oxidative stress and
      accelerating hepatocyte regeneration.

PMID- 21725987
TI  - A unique Golgi apparatus distribution may be a marker for osteogenic
      differentiation of hDP-MSCs.
AB  - Stem cell markers are utilized to isolate or identify stem cells. So far, many
      stem-cell-specific markers have been described, although some of them turned out
      to be not as specific as it was originally proposed. In this study, we sought to
      search for a specific stem cell marker that would be phenotypically helpful,
      characteristically specific, economically affordable and easy to use. Because
      organelles are one of the major characteristics of eukaryotic cells, we asked the
      question of whether organelle characteristics might be a useful tool for stem
      cell characterization. We studied distribution and characteristics of the
      endoplasmic reticulum, the mitochondria and the Golgi apparatus in human dental
      pulp-derived mesenchymal stem cells before and during osteogenic differentiation.
      Although it was not possible to find a useful macromolecular marker for stem cell
      characterization, we found that during osteogenic differentiation, the stem cells
      changed their Golgi characteristics and displayed a unique in vivo pattern. We
      analysed these unique Golgi structures and proposed a potential osteogenic
      differentiation marker for human dental-pulp-derived mesenchymal stem cells. This
      pattern may be used in the evaluation of osteogenic differentiation.

PMID- 21725988
TI  - Changes in hepatitis A and B vaccination rates in adult patients with chronic
      liver diseases and diabetes in the U.S. population.
AB  - Professional societies recommend hepatitis A and hepatitis B immunization for
      individuals with chronic liver disease (CLD), but the degree of implementation is
      unknown. Data were obtained from the National Health and Nutrition Examination
      Surveys (NHANES) conducted in 1999-2008. For the entire study population and for
      those with CLD and diabetes, we determined the rates and independent predictors
      of history of hepatitis A and hepatitis B (HepA and HepB) vaccinations, of their
      effectiveness, and of seroprevalence of hepatitis A antibody and anti-HB surface
      antibody. In total, 24,871 participants from NHANES were included: 14,886 (1999
      2004) and 9,985 (2005-2008). Of these individuals, 14.0% had CLD and 8.6% had
      diabetes. During the study period, HepA vaccination in CLD increased from 13.3%
      +/- 1.0% to 20.0% +/- 1.5%, HepB vaccination increased from 23.4% +/- 1.2% to
      32.1% +/- 1.5%. Of subtypes of CLD, HepA vaccination rates increased only in
      nonalcoholic fatty liver disease (NAFLD), whereas HepB vaccination increased for
      patients with hepatitis C and nonalcoholic fatty liver disease. In the diabetic
      cohort, HepA vaccination rates increased from 9.3% +/- 1.1% to 15.4% +/- 1.7% and
      HepB rates increased from 15.2% +/- 1.5% to 22.4% +/- 1.7%. All changes were
      similar to those observed in the general population. The quality measure (QM) for
      HepA in the general population decreased from 44.4% +/- 1.2% in 1999-2004 to
      41.7% +/- 1.9% in 2005-2008, and similar changes were noted for all subcohorts.
      On the other hand, QM for HepB increased from 31.7% +/- 0.9% to 40.7% +/- 1.0% in
      the population, whereas no changes in QM were noted in any diagnostic cohort
      except for NAFLD. CONCLUSIONS: Although vaccination rates in CLD and diabetic
      cohorts are increasing, they remain low. Given the public health implications of
      acute hepatitis A and hepatitis B in patients with CLD, better implementation of
      the vaccination recommendations for these populations is warranted.

PMID- 21725990
TI  - Human hepatic stellate cells are liver-resident antigen-presenting cells.

PMID- 21725989
TI  - Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes
      steatosis and hepatocellular carcinoma in mice.
AB  - Growth hormone (GH)-activated signal transducer and activator of transcription 5
      (STAT5) and the glucocorticoid (GC)-responsive glucocorticoid receptor (GR) are
      important signal integrators in the liver during metabolic and physiologic
      stress. Their deregulation has been implicated in the development of metabolic
      liver diseases, such as steatosis and progression to fibrosis. Using liver
      specific STAT5 and GR knockout mice, we addressed their role in metabolism and
      liver cancer onset. STAT5 single and STAT5/GR double mutants developed steatosis,
      but only double-mutant mice progressed to liver cancer. Mechanistically, STAT5
      deficiency led to the up-regulation of prolipogenic sterol regulatory element
      binding protein 1 (SREBP-1) and peroxisome proliferator activated receptor gamma
      (PPAR-gamma) signaling. Combined loss of STAT5/GR resulted in GH resistance and
      hypercortisolism. The combination of both induced expression of adipose tissue
      lipases, adipose tissue lipid mobilization, and lipid flux to the liver, thereby
      aggravating STAT5-dependent steatosis. The metabolic dysfunctions in STAT5/GR
      compound knockout animals led to the development of hepatic dysplasia at 9 months
      of age. At 12 months, 35% of STAT5/GR-deficient livers harbored dysplastic
      nodules and ~ 60% hepatocellular carcinomas (HCCs). HCC development was
      associated with GH and insulin resistance, enhanced tumor necrosis factor alpha
      (TNF-alpha) expression, high reactive oxygen species levels, and augmented liver
      and DNA damage parameters. Moreover, activation of the c-Jun N-terminal kinase 1
      (JNK1) and STAT3 was prominent. CONCLUSION: Hepatic STAT5/GR signaling is crucial
      for the maintenance of systemic lipid homeostasis. Impairment of both signaling
      cascades causes severe metabolic liver disease and promotes spontaneous hepatic
      tumorigenesis.

PMID- 21725991
TI  - The assessment of serum hepatitis C virus RNA 12 weeks after the end of treatment
      using TaqMan polymerase chain reaction is less relevant than after 24 weeks for
      predicting sustained virological response.

PMID- 21725992
TI  - Seven cases of autoimmune hepatitis that developed after drug-induced liver
      injury.

PMID- 21725993
TI  - SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic
      circadian clock and energy metabolism.
AB  - Many aspects of energy metabolism, including glucose and lipid homeostasis and
      mitochondrial oxidative metabolism, are under precise control by the mammalian
      circadian clock. However, the molecular mechanism for coordinate integration of
      the circadian clock and various metabolic pathways is poorly understood. Here we
      show that BAF60a, a chromatin-remodeling complex subunit, is rhythmically
      expressed in the liver of mice. Mice with liver-specific knockdown of BAF60a show
      abnormalities in the rhythmic expression pattern of clock and metabolic genes and
      in the circulating metabolite profile. Consistently, knockdown of BAF60a impairs
      the oscillation of clock genes in serum-shocked HepG(2) cells. At the molecular
      level, BAF60a activates Bmal1 and G6Pase transcription by way of the coactivation
      of retinoid-related orphan receptor alpha (RORalpha). In addition, BAF60a is
      present near ROR response elements (RORE) on the proximal Bmal1 and G6Pase
      promoters and turns the chromatin structure into the active state. CONCLUSION:
      Our data suggest a critical role for BAF60a in the coordinated regulation of
      hepatic circadian clock and energy metabolism in mammals.

PMID- 21725994
TI  - PUMA-mediated apoptosis drives chemical hepatocarcinogenesis in mice.
AB  - Hepatocyte death and proliferation contribute to hepatocellular carcinoma
      development after carcinogen exposure or chronic liver inflammation. However, the
      role and the molecular targets of hepatocyte death in relation to compensatory
      proliferation have not been fully characterized. In this study, we investigated
      the role of p53 up-regulated modulator of apoptosis (PUMA), a BH3-only protein
      important for both p53-dependent and -independent apoptosis, in a
      diethylnitrosamine (DEN)-induced liver carcinogenesis model. PUMA deficiency
      significantly decreased the multiplicity and size of liver tumors. DEN treatment
      induced p53-independent PUMA expression, PUMA-dependent hepatocyte death, and
      compensatory proliferation. Furthermore, inhibition or deletion of c-jun N
      terminal kinase 1 (JNK1) abrogated PUMA induction, hepatocyte death, and
      compensatory proliferation. CONCLUSION: These results provide direct evidence
      that JNK1/PUMA-dependent apoptosis promotes chemical hepatocarcinogenesis through
      compensatory proliferation, and suggest apoptotic inducers as potential
      therapeutic targets in liver injury and cancer.

PMID- 21725995
TI  - Biomarkers of liver fibrosis: what lies beneath the receiver operating
      characteristic curve?
AB  - Noninvasive biomarkers of liver fibrosis represent an intense area of research
      with the goals of improving patient care, disease stratification, and aiding the
      development of future antifibrotic therapies. Despite the rapid progress in
      recent years, there remain questions about how diagnostic studies are designed,
      statistical methods to account for spectrum bias, clinically relevant thresholds
      of fibrosis that should be delineated, how diagnostics can be improved, and
      strengthening the reference test to judge emerging biomarkers. This review
      discusses the current methods to address these issues and where further progress
      is needed.

PMID- 21725996
TI  - Inflammation-associated interleukin-6/signal transducer and activator of
      transcription 3 activation ameliorates alcoholic and nonalcoholic fatty liver
      diseases in interleukin-10-deficient mice.
AB  - Alcoholic and nonalcoholic steatohepatitis are characterized by fatty liver plus
      inflammation. It is generally believed that steatosis promotes inflammation,
      whereas inflammation in turn aggregates steatosis. Thus, we hypothesized the
      deletion of interleukin (IL)-10, a key anti-inflammatory cytokine, exacerbates
      liver inflammation, steatosis, and hepatocellular damage in alcoholic and
      nonalcoholic fatty liver disease models that were achieved via feeding mice with
      a liquid diet containing 5% ethanol for 4 weeks or a high-fat diet (HFD) for 12
      weeks, respectively. IL-10 knockout (IL-10(-/-)) mice and several other strains
      of genetically modified mice were generated and used. Compared with wild-type
      mice, IL-10(-/-) mice had greater liver inflammatory response with higher levels
      of IL-6 and hepatic signal transducer and activator of transcription 3 (STAT3)
      activation, but less steatosis and hepatocellular damage after alcohol or HFD
      feeding. An additional deletion of IL-6 or hepatic STAT3 restored steatosis and
      hepatocellular damage but further enhanced liver inflammatory response in IL-10(
      /-) mice. In addition, the hepatic expression of sterol regulatory element
      binding protein 1 and key downstream lipogenic proteins and enzymes in fatty acid
      synthesis were down-regulated in IL-10(-/-) mice. Conversely, IL-10(-/-) mice
      displayed enhanced levels of phosphorylated adenosine monophosphate-activated
      protein kinase and its downstream targets including phosphorylated acetyl
      coenzyme A carboxylase and carnitine palmitoyltransferase 1 in the liver. Such
      dysregulations were corrected in IL-10(-/-) IL-6(-/-) or IL-10(-/-) STAT3(Hep-/-)
      double knockout mice. CONCLUSION: IL-10(-/-) mice are prone to liver inflammatory
      response but are resistant to steatosis and hepatocellular damage induced by
      ethanol or HFD feeding. Resistance to steatosis in these mice is attributable to
      elevation of inflammation-associated hepatic IL-6/STAT3 activation that
      subsequently down-regulates lipogenic genes but up-regulates fatty acid oxidation
      associated genes in the liver.

PMID- 21725998
TI  - Micrometer-scale photonic circuit components based on propagation of exciton
      polaritons in organic dye nanofibers.

PMID- 21725997
TI  - Inflammatory response to liver fluke Opisthorchis viverrini in mice depends on
      host master coregulator MTA1, a marker for parasite-induced cholangiocarcinoma in
      humans.
AB  - Based on the recently established role for the master coregulator MTA1 and MTA1
      containing nuclear remodeling complexes in oncogenesis and inflammation, we
      explored the links between parasitism by the carcinogenic liver fluke
      Opisthorchis viverrini and this coregulator using both an Mta1(-/-) mouse model
      of infection and a tissue microarray of liver fluke-induced human
      cholangiocarcinomas (CCAs). Intense foci of inflammation and periductal fibrosis
      in the liver and kidneys of wild-type Mta1(+/+) mice were evident at 23 days
      postinfection with O. viverrini. In contrast, little inflammatory response was
      observed in the same organs of infected Mta1(-/-) mice. Livers of infected
      Mta1(+/+) mice revealed strong up-regulation of fibrosis-associated markers such
      as cytokeratins 18 and 19 and annexin 2, as determined both by immunostaining and
      by reverse-transcription polymerase chain reaction compared with infected Mta1(-/
      ) mice. CD4 expression was up-regulated by infection in the livers of both
      experimental groups; however, its levels were several-fold higher in the
      Mta1(+/+) mice than in infected Mta1(-/-) mice. Mta1(-/-) infected mice also
      exhibited significantly higher systemic and hepatic levels of host cytokines such
      as interleukin (IL)-12p70, IL-10, and interferon-gamma compared with the levels
      of these cytokines in the Mta1(+/+) mice, suggesting an essential role of MTA1 in
      the cross-regulation of the Th1 and Th2 responses, presumably due to chromatin
      remodeling of the target chromatin genes. Immunohistochemical analysis of ~ 300
      liver tissue cores from confirmed cases of O. viverrini-induced CCA showed that
      MTA1 expression was elevated in >80% of the specimens. CONCLUSION: These findings
      suggest that MTA1 status plays an important role in conferring an optimal
      cytokine response in mice following infection with O. viverrini and is a major
      player in parasite-induced CCA in humans.

PMID- 21725999
TI  - A novel, bipolar polymeric host for highly efficient blue electrophosphorescence:
      a non-conjugated poly(aryl ether) containing triphenylphosphine oxide units in
      the electron-transporting main chain and carbazole units in hole-transporting
      side chains.

PMID- 21726000
TI  - Towards all-soft matter circuits: prototypes of quasi-liquid devices with
      memristor characteristics.

PMID- 21726001
TI  - Preparation of hierarchical mesocrystalline DL-lysine.HCl-poly(acrylic acid)
      hybrid thin films.

PMID- 21726002
TI  - Sandwich-like, graphene-based titania nanosheets with high surface area for fast
      lithium storage.

PMID- 21726003
TI  - Controlled fabrication and water collection ability of bioinspired artificial
      spider silks.

PMID- 21726004
TI  - Equiangular hexagon-shape-controlled synthesis of graphene on copper surface.

PMID- 21726005
TI  - Design of a cellular-uptake-shielding "plug and play" template for photo
      controllable drug release.

PMID- 21726006
TI  - 17O NMR and computational study of a tetrasiliconiobate ion,
      [H(2+x)Si4Nb16O56](14-x)-.
AB  - Rates of oxygen-isotope exchange were measured in the tetrasiliconiobate ion
      [H(2+x)Si(4)Nb(16)O(56)]((14-x)-) to better understand how large oxide ions
      interact with water. The molecule has 19 nonequivalent oxygen sites and is
      sufficiently complex to evaluate hypotheses derived from our previous work on
      smaller clusters. We want to examine the extent to which individual oxygen atoms
      react independently with particular attention given to the order of protonation
      of the various oxygen sites as the pH decreases from 13 to 6. As in our previous
      work, we find that the set of oxygen sites reacts at rates that vary over
      approximately 10(4) across the molecule at 6<pH<13 but with similar pH
      dependencies. There is NMR evidence of an intra- or intermolecular reaction at
      pH~7, where new peaks began to slowly form without losing the (17)O isotopic tag,
      and at pH <= 6 these new peaks formed rapidly. The oxygen atoms bonded to silicon
      atoms began to isotopically exchange at pH 9 and below. The (17)O NMR peak
      positions also vary considerably with pH for some, but not all, nonequivalent
      oxygen sites. This variation could be only partly accounted by electronic
      calculations, which indicate that oxygen atoms should shift similarly upon
      protonation. Instead, we see that some sites change enormously with pH, whereas
      other, similarly coordinated oxygen atoms are less affected, suggesting that
      either some protons are exchanging so rapidly that the oxygen sites are seeing an
      averaged charge, or that counterions are modulating the effect of the coordinated
      protons.

PMID- 21726007
TI  - Towards libraries of luminescent lanthanide complexes and labels from generic
      synthons.
AB  - A synthetic approach is developed to obtain families of luminescent lanthanide
      complexes and markers from a generic family of precursors built from nonadentate
      coordination sites. The syntheses of the precursors, based on a directed
      regioselective nucleophilic aromatic substitution on polyfluoropyridines, are
      described. Functionalisation of the synthons on the aromatic moieties allowed the
      introduction of labelling functions and/or the extension of the electronic
      delocalisation, with concomitant changes in the spectroscopic properties. The
      synthesis of two such families of ligands and of some of their complexes of
      Eu(III) and Tb(III) are described, and the photo-physical properties of the
      complexes were measured, revealing excellent luminescence quantum yields reaching
      unity in some cases. For some of these complexes, the emphasis was further put on
      the preparation of an N-hydroxylsuccinimide (NHS) ester as activated function for
      labelling. The Tb and La complexes in the NHS activated form were synthesized and
      fully characterized. The labelling was first demonstrated on amino functionalized
      polymer beads and characterized by time-resolved luminescence microscopy. In a
      second step, the activated Tb complex was used for the labelling of GFR44
      monoclonal antibody, and was applied to the detection of carcinoembryonic
      antigene (CEA) within the frame of a time-resolved fluoroimmunoassay. Comparison
      with a commercially available kit based on a europium cryptate as energy donor
      confirms the efficiency of Tb to act as an energy donor with an unoptimised 35%
      increase of the detection efficiency.

PMID- 21726008
TI  - Amplified surface plasmon resonance based DNA biosensors, aptasensors, and Hg2+
      sensors using hemin/G-quadruplexes and Au nanoparticles.
AB  - Thiolated nucleic acid hairpin nanostructures that include in their stem region a
      "caged" G-quadruplex sequence, and in their single-stranded loop region
      oligonucleotide recognition sequences for DNA, adenosine monophosphate (AMP), or
      Hg(2+)  ions were linked to bare Au surfaces or to Au nanoparticles (NPs) linked
      to Au surfaces. The opening of the hairpin nanostructures associated with the
      bare Au surface by the complementary target DNA, AMP substrate, or Hg(2+)  ions,
      in the presence of hemin, led to the self-assembly of hemin/G-quadruplexes on the
      surface. The resulting dielectric changes on the surface exhibited shifts in the
      surface plasmon resonance (SPR) spectra, thus providing a readout signal for the
      recognition events. A similar opening of the hairpin nanostructures, immobilized
      on the Au NPs associated with the Au surface, by the DNA, AMP, or Hg(2+)  led to
      an ultrasensitive SPR-amplified detection of the respective analytes. The
      amplification originated from the coupling between the localized surface plasmon
      associated with the NPs and the surface plasmon wave, an effect that
      cooperatively amplifies the SPR shifts that result from the formation of the
      hemin/G-quadruplexes. The different sensing platforms reveal impressive
      sensitivities and selectivities toward the target analytes.

PMID- 21726009
TI  - Noncovalent water-based materials: robust yet adaptive.
AB  - The adaptive properties of noncovalent materials allow easy processing, facile
      recycling, self-healing, and stimuli responsiveness. However, the poor robustness
      of noncovalent systems has hampered their use in real-life applications. In this
      Concept Article we discuss the possibility of creating robust noncovalent arrays
      by utilizing strong hydrophobic interactions. We describe examples from our work
      on aqueous assemblies based on aromatic amphiphiles with extended hydrophobic
      cores. These arrays exhibit fascinating properties, including robustness,
      multiple stimuli-responsiveness, and pathway-dependent self-assembly. We have
      shown that this can lead to functional materials (filtration membranes) rivaling
      covalent systems. We anticipate that water-based noncovalent materials have the
      potential to replace or complement conventional polymer materials in various
      fields, and to promote novel applications that require the combination of
      robustness and adaptivity.

PMID- 21726010
TI  - Simultaneous end-on/side-on coordination modes of a diphosphorus tetrahedral
      complex imposed by pre-organization of oligometallic Cu(I) acceptors.
AB  - The reaction of the [{CpMo(CO)(2)}(2)(MU,eta(2):eta(2)-P(2))]
      (Cp=cyclopentadienyl) metallo-ligand 2 with pre-organized Cu(I) bi- and
      trimetallic precursors afforded new coordination complexes with unprecedented
      coordination modes for a Mo(2)P(2) complex. Variable-temperature solution and
      solid-state (31)P NMR spectroscopy measurements were performed and X-ray
      diffraction studies revealed an eta(2):eta(1) coordination mode for the Mo(2)P(2)
      unit of 2 in the Cu(I) bimetallic complexes 3 and 4. DFT calculations were
      carried out to highlight the bonding situation of this unprecedented coordination
      mode in the Cu(I) bimetallic compound 3. It is built up from a side-on
      coordination of the P-P sigma bond to one copper ion and from the interaction of
      the lone pair of one phosphorus atom with the second copper ion. The remaining
      available lone pair of the second phosphorus atom can be involved as well to
      interact with an additional metal centre, as evidenced in the Cu(I) trimetallic
      compound 5 in which an eta(2):eta(1):eta(1) coordination mode of the ligand 2 is
      observed. Derivative 3 can be used as a molecular clip to obtain discrete pi
      stacked dimers through a ligand exchange reaction between acetonitrile ligands
      and cyano-capped pi-conjugated systems, indicating the stability of the new
      eta(2):eta(1) coordination mode.

PMID- 21726011
TI  - Interference with p53 functions in human viral infections, a target for novel
      antiviral strategies?
AB  - Viral infections cause a major stress in host cells. The cellular responses to
      stress are mediated by p53, which by deregulation of cell cycle and apoptosis,
      may also be part of the host cell reaction to fight infections. Therefore, during
      evolutionary viral adaptation to host organisms, viruses have developed
      strategies to manipulate host cell p53 dependent pathways to facilitate their
      viral life cycles. Thus, interference with p53 function is an important component
      in viral pathogenesis. Many viruses have proteins that directly affect p53,
      whereas others alter the regulation of p53 in an indirect manner, mediated by
      Hdm2 or Akt, or induction of interferon. Rescue of p53 activity is becoming an
      area of therapeutic development in oncology. It might be feasible that
      manipulation of p53 mediated responses can become a therapeutic option to limit
      viral replication or dissemination. In this report, the mechanisms by which viral
      proteins manipulate p53 responses are reviewed, and it is proposed that a
      pharmacological rescue of p53 functions might help to control viral infections.

PMID- 21726013
TI  - Prescription patterns of patients diagnosed with schizophrenia in mental
      hospitals in Tashkent/Uzbekistan and in four German cities.
AB  - PURPOSE: Little is known about psychopharmacological prescription practice in low
      income countries. The present study aimed for an analysis of pharmacological
      treatment strategies for inpatients with schizophrenia in Tashkent, the capital
      city of Uzbekistan, facing a low-income situation as compared with four German
      cities in a high-income Western situation. METHODS: We conducted a cross
      sectional quantitative survey of age, gender, diagnoses, and psychotropic
      medication of 845 urban psychiatric inpatients of the Tashkent psychiatric
      hospital and of 922 urban psychiatric inpatients in four German cities on 1 day
      in October 2008. We compared the current treatment strategies for specific
      diagnostic categories between the two settings. RESULTS: In Tashkent, patients
      diagnosed with schizophrenia were treated with clozapine (66%), haloperidol
      (62%), or both (44%). More than one-third of the patients treated for
      schizophrenia were prescribed amitriptyline. The usual treatment strategy for
      schizophrenia was the combination of two or more antipsychotics (67%). In German
      cities, the preferred antipsychotics for the treatment of schizophrenia were
      olanzapine (21%), clozapine (20%), quetiapine (17%), risperidone (17%), and
      haloperidol (14%); the most common treatment strategy for patients with
      schizophrenia was the combination of antipsychotics and benzodiazepines; 44% of
      the patients were treated with two or more antipsychotics at a time. CONCLUSIONS:
      In both settings, psychotropic combination treatments are common for the
      treatment of schizophrenia contrasting current guideline recommendations. Its
      rationale and effectiveness needs to be tested in further studies.

PMID- 21726012
TI  - Prescription of teriparatide in the UK--a nationwide register study from 2004 to
      2008.
AB  - INTRODUCTION: The objectives were to ascertain the incidence of teriparatide
      prescription in the UK stratified by region and sex, examine the association
      between National Institute for Health and Clinical Excellence (NICE) and European
      Medicines Agency approval and geographic variation in teriparatide prescription,
      and compare the regional rates of teriparatide and oral bisphosphonate use.
      METHODS: Healthcare at Home provided anonymized information on age, sex, year,
      and treating hospital for all UK residents commenced on teriparatide between 1
      January 2004 and 31 December 2008. The crude and age- and sex-adjusted rates of
      teriparatide prescription were calculated for each region. Rates of teriparatide
      prescription for each region, in the year before and in the year after approval
      by NICE and European Medicines Agency, were compared in a multiplicative model
      (likelihood-ratio test) for women and men, respectively. The number of patients
      on oral bisphosphonates in each region was estimated from quantity of oral
      bisphosphonates dispensed in 2007. RESULTS: Compared with that in England, the
      incidence of teriparatide prescription was 54% and 50% higher in Wales and in
      Scotland, respectively. The Northeast and East of England had lowest rate of
      teriparatide use. There was significant geographic variation in increase in
      teriparatide prescription in women after favorable NICE recommendation (p =
      0.0001). In contrast, prescription rates in men increased uniformly across the UK
      (p = 0.15). Geographic variation in oral bisphosphonate prescription did not
      mirror that of teriparatide. CONCLUSION: We report wide geographic variation in
      teriparatide prescription rates within the UK. In a country with government
      funded health care, reasons for this inequality need to be identified.

PMID- 21726014
TI  - Misuse of acetaminophen in the management of dental pain.
AB  - PURPOSE: We highlight the risk associated with acetaminophen misuse in patients
      having dental pain in France based on a series of cases of unintentional
      acetaminophen overdose reported by the Emergency Dental Service of Nancy over a 9
      month period. METHODS: Data were collected by querying the French
      Pharmacovigilance database. Each retrieved clinical data were reviewed by a
      clinician. RESULTS: Thirteen cases of acetaminophen overdose were reported to the
      Regional Pharmacovigilance Center of Lorraine, Nancy, France. Most cases (10/13)
      concerned men aged 20-40 years old. Mild, unspecific clinical symptoms were
      observed in seven of 13 patients. The median value of the supposed ingested dose
      was 137 mg/kg/24 h. Liver enzyme activity was tested in 10 patients and was
      abnormal in four patients. N-acetylcysteine treatment was administered to four
      patients. CONCLUSIONS: We propose that even patients with mild clinical symptoms
      with a supposed ingested dose of acetaminophen greater than 150 mg/kg/24 h should
      be referred to an emergency department and that liver enzyme activity should be
      analyzed. No case of liver failure was observed during our short survey. However,
      hepatotoxicity of repeated supratherapeutic ingestion of acetaminophen was
      suspected in four patients. Patients and practitioners should thus be better
      informed about the risk of unintentional acetaminophen overdose following
      supratherapeutic acetaminophen ingestion.

PMID- 21726015
TI  - Sleep problems in cancer patients: prevalence and association with distress and
      pain.
AB  - BACKGROUND: Although it is increasingly recognized that cancer patients often
      have sleep problems, we lack data on their prevalence and associations in
      representative clinical populations. We aimed to determine (i) the prevalence of
      sleep problems amongst outpatients of a cancer centre and (ii) the association
      with medical variables, emotional distress and pain. METHODS: Secondary analysis
      of self-report and medical data on 2862 cancer centre outpatients. Sleep problems
      were identified using the sleep item from the Patient Health Questionnaire-9:
      'Over the last two weeks, how often have you been bothered by trouble falling or
      staying asleep or sleeping too much?' scored on a four-point frequency scale.
      Emotional distress was measured using the Hospital Anxiety and Depression Scale
      and pain using the subscale of the European Organisation for Research and
      Treatment of Cancer Quality of Life Core 30 questionnaire. Medical data were
      obtained from the cancer centre clinical database. RESULTS: Sleep problems
      (bothered more than half the days during the previous 2 weeks) were reported by
      30.2% (865/2862, 95% CI = 28.5 to 31.9) of the patients. They were common in both
      patients with active cancer (34.5%) and in cancer survivors (28.0%). There was
      only a modest association with cancer site and treatment status, but there was a
      strong association with pain (odds ratio = 2.7, 95% CI = 2.2 to 3.4) and
      emotional distress (odds ratio = 4.5, 95% CI = 3.7 to 5.6). CONCLUSIONS: Sleep
      problems are common in cancer outpatients and are strongly associated with pain
      and emotional distress. A combined approach to the management of sleep, pain and
      emotional distress is indicated. Copyright (c) 2011 John Wiley & Sons, Ltd.

PMID- 21726016
TI  - A test of the psychometric properties of the cancer locus of control scale in
      Greek patients with advanced cancer.
AB  - OBJECTIVE: The study aimed to assess the psychometric properties of the Cancer
      Locus of Control (CLOC) scale on a Greek sample of advanced cancer patients.
      METHODS: The scale was translated with the forward-backward procedure to Greek.
      The CLOC scale was administered to 140 advanced cancer patients. It was
      administered twice, with a 3-day interval, to 100 (of the 140) eligible patients
      with advanced cancer. Together with the CLOC scale, the patients also completed
      the Greek Mental Adjustment to Cancer (G-MAC) scale. Confirmatory factor analysis
      was carried out using the AMOS 7.0 analysis. The reliability was assessed by the
      internal consistency (Cronbach's alpha coefficients), test-retest (Spearman's r
      value) of the instrument, and inter-item correlations. Construct validity was
      assessed using the G-MAC scale, interscale correlations, item-scale correlations,
      and scales-total correlations. RESULTS: The homogeneity of the subscales proved
      to be satisfactory (alpha coefficient ranged from 0.713 to 0.786). Overall test
      retest reliability was satisfactory at p < 0.0005. Construct validity has shown
      moderate correlations with G-MAC p < 0.0005. Interscale and inter-item
      correlations were satisfactory at p < 0.05. CONCLUSIONS: The results suggest that
      the Greek version of CLOC administered in cancer patients treated in a palliative
      care unit is a reliable and valid clinical instrument.

PMID- 21726017
TI  - An individual-based versus group-based exercise and counselling intervention for
      improving quality of life in breast cancer survivors. A feasibility and efficacy
      study.
AB  - BACKGROUND: Cancer and its treatments produce lingering side-effects that
      undermine the quality of life (QOL) of survivors. Exercise and psycho-therapies
      increase QOL among survivors, however, research is needed to identify
      intervention characteristics most associated with such improvements. OBJECTIVE:
      This research aimed to assess the feasibility of a 9 week individual or group
      based exercise and counselling program, and to examine if a group based
      intervention is as effective at improving the QOL of breast cancer survivors as
      an individual-based intervention. METHODS: A three group design was implemented
      to compare the efficacy of a 9 week individual (IEC n = 12) and group based
      exercise and counselling (GEC n = 14) intervention to a usual care (UsC n = 10)
      group on QOL of thirty-six breast cancer survivors. RESULTS: Across all groups,
      90% of participants completed the interventions, with no adverse effects
      documented. At the completion of the intervention, there was a significant
      difference between groups for change in global QOL across time (p < 0.023), with
      IEC improving significantly more (15.0 points) than the UsC group (1.8 points).
      The effect size was moderate (0.70). Although the GEC improved QOL by almost 10.0
      points, this increase did not reach significance. Both increases were above the
      minimally important difference of 7-8 points. CONCLUSION: These preliminary
      results suggest a combined exercise and psychological counseling program is both
      a feasible and acceptable intervention for breast cancer survivors. Whilst both
      the individual and group interventions improved QOL above the clinically
      important difference, only the individual based intervention was significant when
      compared to UsC.

PMID- 21726018
TI  - Cross-cultural validation of a Patient Satisfaction with Interpersonal
      Relationship with Navigator measure: a multi-site patient navigation research
      study.
AB  - BACKGROUND: Patient navigators are trained to help patients effectively access
      and use healthcare resources in order to facilitate timely completion of
      recommended cancer screening, diagnostic care, and treatment. Patient navigators
      provide logistic, instrumental, and psychosocial support to cancer patients. Yet
      few studies have examined patient-navigator relationships, particularly for
      Spanish-speaking patients with low English proficiency. We aimed to validate a
      Spanish version of the Patient Satisfaction with Interpersonal Relationship with
      Navigator (PSN-I-Sp) scale. METHODS: We translated and back-translated the PSN-I
      into Spanish and administered the resulting PSN-I-Sp to 222 Spanish-fluent
      participants. We conducted a principal components analysis and assessed
      Cronbach's coefficient alpha (alpha) to evaluate the latent structure and the
      internal consistency of the PSN-I-Sp. We also completed correlation analyses to
      examine divergence and convergence of the PSN-I-Sp with the Spanish version of
      the Patient Satisfaction with Cancer-Related Care (PSCC-Sp) and the patients'
      demographics. RESULTS: The principal components analysis revealed a one
      dimensional PSN-I-Sp measure that explained 82.0% of the variance. The
      reliability assessment revealed high internal consistency (alpha = 0.97). The PSN
      I-Sp demonstrated good face validity and adequate convergent and divergent
      characteristics as indicated by a moderate correlation with scores on the PSCC-Sp
      (all ps < 0.0001) and a non-statistically significant correlation with marital
      status (all p > 0.05). CONCLUSION: The PSN-I-Sp is a valid and internally
      consistent measure of satisfaction with interpersonal relationship with a patient
      navigator for Spanish-speaking participants.

PMID- 21726020
TI  - Farewell to the HSAB treatment of ambident reactivity.
AB  - The concept of hard and soft acids and bases (HSAB) proved to be useful for
      rationalizing stability constants of metal complexes. Its application to organic
      reactions, particularly ambident reactivity, has led to exotic blossoms. By
      attempting to rationalize all the observed regioselectivities by favorable soft
      soft and hard-hard as well as unfavorable hard-soft interactions, older
      treatments of ambident reactivity, which correctly differentiated between
      thermodynamic and kinetic control as well as between different coordination
      states of ionic substrates, have been replaced. By ignoring conflicting
      experimental results and even referring to untraceable experimental data, the
      HSAB treatment of ambident reactivity has gained undeserved popularity. In this
      Review we demonstrate that the HSAB as well as the related Klopman-Salem model do
      not even correctly predict the behavior of the prototypes of ambident
      nucleophiles and, therefore, are rather misleading instead of useful guides. An
      alternative treatment of ambident reactivity based on Marcus theory will be
      presented.

PMID- 21726019
TI  - Investigating head and trunk rotation in sitting: a pilot study comparing people
      after stroke and healthy controls.
AB  - BACKGROUND AND PURPOSE: Healthy individuals have a top-down coordination pattern
      when turning while walking; they first rotate the head, then the shoulders, the
      pelvis and, finally, the feet. The aim of this study was to compare spatial and
      temporal characteristics of head and trunk rotation in sitting between people
      early after stroke and healthy participants, and investigate change over time.
      METHODS: This was a pilot, quantitative, longitudinal study. We recruited
      participants from stroke wards and local groups. People with stroke were assessed
      at 3, 6 and 12 weeks after stroke. Healthy participants were examined with the
      same weekly intervals. Participants were in a seated position and were asked
      verbally to rotate their head and look at a visual signal placed at 90 degrees 
      to the left and to the right of the subject. CODAmotion (Charnwood Dynamics Ltd,
      Rothley, UK) was used for 3-D motion recording and analysis. RESULTS: Healthy
      participants (two women and four men; mean age 66 years) showed significant
      rotation of the head before rotation of the shoulders at all three time points;
      people with stroke (one woman and five men; mean age 71 years) did not show this
      top-down pattern of movement. There was no significant difference between start
      times of head and shoulder rotation at 3 (p = 0.167), 6 (p = 0.084) and 12 weeks
      after stroke (p = 0.062). Conclusions. The results of our pilot study warrant
      further investigation into the recovery and pattern of axial coordination after
      stroke. Future studies could provide insight into the mechanisms behind impaired
      postural control in people after stroke.

PMID- 21726021
TI  - Gold alpha-oxo carbenoids in catalysis: catalytic oxygen-atom transfer to
      alkynes.
AB  - An overview of reactive gold alpha-oxo carbenoid intermediates in the gold
      catalyzed functionalization of alkynes is presented. Such intermediates can be
      generated from inter- and intramolecular oxidation of alkynes by nucleophilic
      oxygen-atom donor groups, such as amine N-oxides, pyridine N-oxides, nitrones,
      nitro compounds, sulfoxides, and epoxides. These O-atom transfer processes occur
      by gold-mediated addition-elimination reactions. In catalytic systems, alpha-oxo
      carbenoids can undergo nucleophilic attack by imine, arene, and migrating hydride
      as well as alkyl groups, leading to cascade reactions and the construction of new
      skeletons. The facile construction of C-E (E=C, N, S, or O) bonds makes it an
      attractive step-economic approach to value-added molecules from readily available
      starting materials. The scope, mechanisms, and reactivity of such alpha-oxo
      carbenoid species are discussed. The remarkable diversity of structures
      accessible is demonstrated with various recent examples.

PMID- 21726022
TI  - Synthesis of free-standing, monolayered organometallic sheets at the air/water
      interface.

PMID- 21726023
TI  - Gold catalysis in micellar systems.

PMID- 21726024
TI  - Capture of NO by a Frustrated Lewis Pair: a new type of persistent N-oxyl
      radical.

PMID- 21726025
TI  - Hybrid-state dynamics of gold nanorods/dye J-aggregates under strong coupling.

PMID- 21726026
TI  - Total synthesis of dinophysistoxin-2 and 2-epi-dinophysistoxin-2 and their PPase
      inhibition.

PMID- 21726027
TI  - Rendering Schrock-type molybdenum alkylidene complexes air stable: user-friendly
      precatalysts for alkene metathesis.

PMID- 21726028
TI  - Biosynthesis of himastatin: assembly line and characterization of three
      cytochrome P450 enzymes involved in the post-tailoring oxidative steps.

PMID- 21726029
TI  - Chiral sulfoxide-olefin ligands: completely switchable stereoselectivity in
      rhodium-catalyzed asymmetric conjugate additions.

PMID- 21726030
TI  - Fused indolines by palladium-catalyzed asymmetric C-C coupling involving an
      unactivated methylene group.

PMID- 21726031
TI  - Spectroscopic characterization of the isolated iron-molybdenum cofactor (FeMoco)
      precursor from the protein NifEN.

PMID- 21726033
TI  - Ion-channel modulators: more diversity than previously thought.
AB  - Ion-channel function can be modified in various ways. For example, numerous
      studies have shown that currents through voltage-gated ion channels are affected
      by pore block or modification of voltage dependence of activation/inactivation.
      Recent experiments performed on various ion channels show that allosteric
      modulation is an important mechanism for affecting channel function. For
      instance, in K(Ca)2 (formerly SK) channels, the prototypic "blocker" apamin
      prevents conduction by an allosteric mechanism, while TRPV1 channels are
      prevented from closing by a tarantula toxin, DkTx, through an interaction with
      residues located away from the selectivity filter. The recent evidence,
      therefore, suggests that in several ion channels, the region around the outer
      mouth of the pore is rich in binding sites and could be exploited
      therapeutically. These discoveries also suggest that the pharmacological
      vocabulary should be adapted to define these various actions.

PMID- 21726034
TI  - Long-range distance determination in a DNA model system inside Xenopus laevis
      oocytes by in-cell spin-label EPR.

PMID- 21726035
TI  - Identification of the first bacterial monoterpene cyclase, a 1,8-cineole
      synthase, that catalyzes the direct conversion of geranyl diphosphate.

PMID- 21726036
TI  - Ultrafast electron transfer from photoexcited CdSe quantum dots to
      methylviologen.
AB  - The ultrafast charge separation at the quantum dot (QD)/molecular acceptor
      interface was investigated in terms of acceptor concentration and the size of the
      QD. Time-resolved experiments revealed that the electron transfer (ET) from the
      photoexcited QD to the molecular acceptor methylviologen (MV(2+)) occurs on the
      fs time scale for large acceptor concentrations and that the ET rate is strongly
      reduced for low concentrations. The increase in the acceptor concentration is
      accompanied with a growth in the overlap of donor and acceptor wavefunctions,
      resulting in a faster reaction until the MV(2+) concentration reaches a
      saturation limit of 0.3-0.4 MV(2+) nm(-2). Moreover, we found significant QD size
      dependence of the ET reaction, which is explained by a change of the free energy
      (DeltaG).

PMID- 21726037
TI  - Neem oil (Azadirachta indica) nanoemulsion--a potent larvicidal agent against
      Culex quinquefasciatus.
AB  - BACKGROUND: Nanoemulsion composed of neem oil and non-ionic surfactant Tween 20,
      with a mean droplet size ranging from 31.03 to 251.43 nm, was formulated for
      various concentrations of the oil and surfactant. The larvicidal effect of the
      formulated neem oil nanoemulsion was checked against Culex quinquefasciatus.
      RESULTS: O/W emulsion was prepared using neem oil, Tween 20 and water.
      Nanoemulsion of 31.03 nm size was obtained at a 1:3 ratio of oil and surfactant,
      and it was found to be stable. The larger droplet size (251.43 nm) shifted to a
      smaller size of 31.03 nm with increase in the concentration of Tween 20. The
      viscosity of the nanoemulsion increased with increasing concentration of Tween
      20. The lethal concentration (LC50) of the nanoemulsion against Cx.
      quinquefasciatus was checked for 1:0.30, 1:1.5 and 1:3 ratios of oil and
      surfactant respectively. The LC50 decreased with droplet size. The LC50 for the
      ratio 1:3 nanoemulsions was 11.75 mg L(-1). CONCLUSION: The formulated
      nanoemulsion of 31.03 nm size was found to be an effective larvicidal agent. This
      is the first time that a neem oil nanoemulsion of this droplet size has been
      reported. It may be a good choice as a potent and selective larvicide for Cx.
      quinquefasciatus.

PMID- 21726038
TI  - Optimisation of a semiochemical slow-release alginate formulation attractive
      towards Aphidius ervi Haliday parasitoids.
AB  - BACKGROUND: Optimisation of alginate formulations is described in order to
      develop semiochemical (E-beta-farnesene and E-beta-caryophyllene) slow-release
      devices in biological control approaches by attracting predators and parasitoids
      of aphids. Various formulation criteria were optimised with respect to
      semiochemical encapsulation capacity. Moreover, the optimised formulation was
      characterised by texturometry and confocal microscopy. The slow-release rates of
      semiochemicals were calculated in laboratory controlled conditions. The
      attractiveness of semiochemical formulations towards Aphidius ervi was
      demonstrated by olfactometry. RESULTS: Two major parameters were highlighted in
      encapsulation optimisation: the type of alginate (Sigma L) and the type of
      crosslinker ion (Ca(2+)). Other formulation parameters were optimised: ionic
      strength (0.5 M), Ca(2+) (0.2 M) and alginate (1.5%) concentrations and the
      maturation time of beads in CaCl(2) solution (48 h). After physical
      characterisation of beads, semiochemical slow-release measurements showed that
      alginate formulations were efficient sesquiterpene releasers, with 503 ug of E
      beta-farnesene and 1791 ug of E-beta-caryophyllene totally released in 35 days.
      The efficiency of semiochemical alginate beads as attractants for female
      parasitoids was demonstrated, with high percentages of attraction for
      semiochemical odours (88 and 90% for E-beta-farnesene and E-beta-caryophyllene
      respectively) and significant statistical results. CONCLUSION: Semiochemical
      alginate beads can be considered as efficient slow-release systems in biological
      control. These formulations could be very useful to attract aphid parasitoids on
      crop fields.

PMID- 21726039
TI  - The escalating threat of Rhizoctonia cerealis, the causal agent of sharp eyespot
      in wheat.
AB  - Rhizoctonia cerealis, the causal agent of sharp eyespot on wheat, was not
      considered to be an important pathogen for many years. Recently, the disease has
      become endemic in many countries except for South America. The disease has
      created a new threat to world wheat production because the damage of wheat sharp
      eyespot has become increasingly severe. In this paper, previous studies on this
      pathogen, including the disease geographical distribution, pathogen
      identification, life cycle, symptoms, favourable environmental conditions,
      effects on wheat yield and control strategy, are reviewed. Such information will
      be helpful in management of sharp eyespot.

PMID- 21726041
TI  - Aptamer-assembled nanomaterials for biosensing and biomedical applications.
AB  - Aptamers represent a class of single-stranded DNA or RNA oligonucleotides that
      play important roles in biosensing and biomedical applications. However, aptamers
      can gain more flexibility as molecular recognition tools by taking advantage of
      the unique chemical and physical properties provided by nanomaterials. Such
      aptamer-nanomaterial conjugates are having an increasing impact in the fields of
      biosensing, bioimaging, and therapy. The recent advances and limitations of
      aptamer-assembled nanomaterials in biosensing and biomedical applications are
      briefly introduced and discussed. 

PMID- 21726042
TI  - Rare-earth upconverting nanobarcodes for multiplexed biological detection.

PMID- 21726043
TI  - Polymersome-loaded capsules for controlled release of DNA.
AB  - The formation of a novel drug-delivery carrier for the controlled release of
      plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized
      with pH-sensitive nanometer-sized polymersomes is reported. The amphiphilic
      diblock copolymer poly(oligoethylene glycol methacrylate)-block-poly(2
      (diisopropylamino)ethyl methacrylate) forms polymersomes at physiological pH, but
      transitions to unimeric polymer chains upon acidification to cellular endocytic
      pH. These polymersomes can thus release an encapsulated payload in response to a
      change in pH from physiological to endocytic conditions. Multicomponent layer-by
      layer capsules are formed by exploiting the ability of tannic acid to act as an
      efficient hydrogen-bond donor for both the polymersomes and poly(N-vinyl
      pyrrolidone) at physiological pH. These capsules show release of a plasmid DNA
      payload encapsulated within the polymersome subcompartments in response to
      changes in pH between physiological and endocytic conditions.

PMID- 21726044
TI  - A proteomic view of the host-pathogen interaction: The host perspective.
AB  - The host-pathogen interaction represents a complex and dynamic biological system.
      The outcome of this interaction is dependent on the microbial pathogen properties
      to establish infection and the ability of the host to control infection. Although
      bacterial pathogens have evolved a variety of strategies to subvert host defense
      functions, several general mechanisms have been shown to be shared among these
      pathogens. As a result, host effectors that are critical for pathogen entry,
      survival and replication inside the host cells have become a new paradigm for
      antimicrobial targeting. This review focuses on the potential utility of a
      proteomics approach in defining the host-pathogen interaction from the host's
      perspective.

PMID- 21726045
TI  - Current methodologies for proteomics of bacterial surface-exposed and cell
      envelope proteins.
AB  - The study of surface-exposed proteins has received increasing attention following
      the advent of genomic sequencing, which in turn has enabled predictive tools and
      facilitated the technologies for their analysis by proteomics. The exterior
      topology of a bacterial pathogen is the interface between the cell and
      environment and thus is the initial mediator for infection, providing an
      important reservoir for components that may be used for novel vaccine development
      as well as the characterization of new drug targets. The study of such biological
      molecules has however, been under-represented in proteomics studies due to the
      difficulty involved in their analysis. Cell-envelope proteins in bacteria are
      typically difficult to characterize due to their low abundance, poor solubility,
      and the problematic isolation of pure surface fractions with only minimal
      contamination. Here, we describe different cell envelope preparations for
      proteomic characterization, focused principally on gel-free technologies.
      Fractionation techniques popularly used in proteomics are also explained with
      emphasis on surface and membrane-derived proteins/peptides. Conditional
      confirmation of localization is also explored with emphasis on different
      prediction algorithms as well as on analyses of surface peptide fractions by the
      use of different search programs and their implications for the unambiguous
      identification of surface-exposed and membrane-embedded proteins. Finally,
      different quantification techniques are discussed that are important for the
      validation of identifications and for highlighting novel proteins that may
      warrant further study by independent techniques.

PMID- 21726046
TI  - Site-specific analysis of bacterial phosphoproteomes.
AB  - Protein phosphorylation on serine, threonine and tyrosine is established as an
      important regulatory modification in bacteria. A growing number of studies
      employing mass spectrometry-based proteomics report large protein phosphorylation
      datasets, providing precise evidence for in-vivo phosphorylation that is
      especially suitable for functional follow-up. Here, we provide an overview of the
      strategies currently used in bacterial phosphoproteomics, with an emphasis on gel
      free proteomics and approaches that enable global detection of phosphorylation
      sites in bacterial proteins. The proteomics technology has matured sufficiently
      to permit routine characterization of phosphoproteomes and phosphopeptides with
      high sensitivity; we argue that the next challenge in the field will be the large
      scale detection of protein kinase and phosphatase substrates and their
      integration into regulatory networks of the bacterial cell.

PMID- 21726047
TI  - Proteomics of a plant pathogen: Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens is an important plant pathogen which belongs to the
      alpha-proteobacteria. In addition, it has served as the main tool for plant
      molecular genetics. Here we focus on three major aspects: (i) proteomic mapping,
      (ii) the use of proteomics for the understanding of the response of A.
      tumefaciens to changes in environmental conditions and (iii) the analysis of the
      changes in genome expression following interaction with the host. These studies
      convey a global outlook on the functional genomics of A. tumefaciens and help to
      understand the physiology of this important organism.

PMID- 21726048
TI  - Investigating pathogen biology at the level of the proteome.
AB  - Bacterial infections are a major cause of morbidity and mortality throughout the
      world. By extending our understanding of the process of bacterial pathogenesis at
      the molecular level new strategies for their treatment and prevention can be
      developed. Proteomic technologies, along with other methods for global gene
      expression analysis, play an important role in understanding the mechanism(s) of
      bacterial pathogenesis. This review highlights the use of proteomics to identify
      protein biomarkers for virulent bacterial isolates and how these biomarkers can
      be correlated with the outcome of bacterial infection. Biomarker identification
      typically looks at the proteomes of bacteria grown under laboratory conditions.
      It is, however, the characterisation of the bacterial proteome during in vivo
      infection of its host that will eventually provide the most significant insights
      into bacterial pathogenesis. Although this area of research has significant
      technical challenges, a number of complementary proteome analytical approaches
      are being developed to identify and characterise the bacterial genes specifically
      expressed in vivo. Ultimately, the development of newly targeted therapies and
      vaccines using specific protein targets identified through proteomic analyses
      will be one of the major practical benefits arising from the proteomic analysis
      of bacterial pathogens.

PMID- 21726049
TI  - A proteomic view of mycobacteria.
AB  - Tuberculosis, the disease caused by Mycobacterium tuberculosis, remains a
      relevant public health issue. This is due mostly to the coepidemiology with
      HIV/AIDS, the appearance of multidrug-resistant strains globally, and failure of
      BCG (bacillus Calmette-Guerin) vaccination to confer complete protection. This
      bacterium was one of the first to have its genome sequenced, yet over a decade
      after the release of the genomic information, the characterization of its
      phylogenetic tree and of different strain variants inside this species revealed
      that much is still needed to be done for a full understanding of the M.
      tuberculosis genome and proteome. Current methods using LC-MS/MS and hybrid high
      resolution mass spectrometers can identify 2400-2800 proteins of the 4000
      predicted genes in M. tuberculosis. In this article, we review relevant details
      of this bacterium's pathology and immunology, describing articles where
      proteomics helped the community to tackle some of the organism biology, from
      understanding strain diversity, cellular structure composition, immunogenicity,
      and host-pathogen interactions. Finally, we will discuss the challenges yet to be
      fulfilled in order to better characterize M. tuberculosis by proteomics.

PMID- 21726050
TI  - Proteomic signatures in antibiotic research.
AB  - Antibiotics disturb the physiological homeostasis of bacterial cells by
      interfering with essential cellular functions or structures. The bacterial
      proteome adjusts quickly in response to antibiotic challenge. This physiological
      response is specifically tailored to overcome the inflicted damage and, thus,
      closely linked to the antibiotic target and mechanism of action. In a way, the
      proteome mirrors the antibiotic insult. This connection can be exploited to guide
      the development of novel antibiotics. By using structurally different
      antibiotics, which cause the same physiological disturbance, proteomic signatures
      diagnostic of the mechanism of action can be defined. These proteomic signatures
      inform about mechanism-related differential protein expression as well as about
      protein modifications. This review recapitulates how antibiotic proteomic
      signatures are established and highlights areas of antibiotic research benefiting
      most from proteomic signatures. Antibacterial research programs designed to
      structurally advance existing antibiotic classes profit from rapid in vivo
      mechanism of action confirmation. What is more, a comprehensive reference
      compendium of antibiotic proteomic signatures allows rapid mechanism of action
      identification of those structurally novel compounds that inhibit known targets.
      Finally, novel proteomic response profiles indicate unprecedented mechanisms.
      Here, the proteome profile provides evidence on the nature of the antibiotic
      caused physiological disturbance leading to testable hypotheses on the mechanism
      of action.

PMID- 21726051
TI  - Proteomics for routine identification of microorganisms.
AB  - The invention of MALDI-TOF-MS enormously contributed to the understanding of
      protein chemistry and cell biology. Without this technique proteomics would most
      likely not be the important discipline it is today. Besides 'true' proteomics,
      MALDI-TOF-MS was applied for the analysis of microorganisms for their taxonomic
      characterization from its beginning. This approach has since been developed as a
      diagnostic tool readily available for routine, high-throughput analysis of
      microbial isolates from clinical specimens by intact-cell mass spectrometry
      (ICMS), the direct analysis of whole bacterial cell without a preceding
      fractionation or separation by chromatography or electrophoresis. ICMS exploits
      the reproducibility of mass fingerprints for individual bacterial and fungal
      strains as well as the high similarity of mass fingerprints within a species.
      Comparison of mass spectral data to genomic sequences emphasized the validity of
      peak patterns as taxonomic markers. Supported by comprehensive databases, MALDI
      TOF-MS-based identification has been widely accepted in clinical laboratories
      within only a few years.

PMID- 21726052
TI  - Combined proteomic and transcriptomic analysis of the response of Bacillus
      anthracis to oxidative stress.
AB  - The endospore-forming Gram-positive pathogen Bacillus anthracis is responsible
      for the usually fatal disease, inhalational anthrax. The success of this pathogen
      is dependent on its ability to subvert elements of the innate immune system of
      its animal hosts. B. anthracis spores, which are the main infective agent, are
      engulfed and germinate in patrolling alveolar macrophages. In order for the
      infection to progress, the resulting vegetative cells must resist the
      antimicrobial oxidative burst mounted by the host NADPH oxidase complex. The
      response of B. anthracis to this and other macrophage-related stresses is
      therefore of major importance to the success of this pathogen, and consequently
      we have analysed the superoxide and peroxide stress stimulons of B. anthracis
      strain UM23C1-2 by means of a combined transcriptomics and proteomics approach.
      The results show distinct patterns of expression in response to paraquat
      (endogenous superoxide) and hydrogen peroxide stress. While the main response to
      paraquat is the induction of iron uptake pathways, the response to peroxide
      predominantly involves the induction of protection and repair mechanisms.
      Comparisons between the responses of B. anthracis and related soil bacterium, B.
      subtilis, reveal differences that are likely to be relevant to their respective
      habitats.

PMID- 21726053
TI  - Proteomics of eukaryotic microorganisms: The medically and biotechnologically
      important fungal genus Aspergillus.
AB  - Fungal species of the genus Aspergillus play significant roles as model organisms
      in basic research, as "cell factories" for the production of organic acids,
      pharmaceuticals or industrially important enzymes and as pathogens causing
      superficial and invasive infections in animals and humans. The release of the
      genome sequences of several Aspergillus sp. has paved the way for global analyses
      of protein expression in Aspergilli including the characterisation of proteins,
      which have not designated any function. With the application of proteomic
      methods, particularly 2-D gel and LC-MS/MS-based methods, first insights into the
      composition of the proteome of Aspergilli under different growth and stress
      conditions could be gained. Putative targets of global regulators led to the
      improvement of industrially relevant Aspergillus strains and so far not described
      Aspergillus antigens have already been discovered. Here, I review the recent
      proteome data generated for the species Aspergillus nidulans, Aspergillus
      fumigatus, Aspergillus niger, Aspergillus terreus, Aspergillus flavus and
      Aspergillus oryzae.

PMID- 21726054
TI  - Quantitative proteomics of microbes: Principles and applications to virulence.
AB  - The rapidly increasing ability to sequence complete genomes of different
      microbial species and strains provides us with information regarding their
      genetic variability. Genetic variability is a mechanism for human pathogens to
      adapt to and avoid the immune system and to also develop resistance to
      antibiotics. However, the assessment of the contributions of individual genetic
      differences to resistance or other phenotypes is not a priori apparent from the
      genomic variability. Quantitative proteomics can provide accurate molecular
      phenotypes of microbes that are difficult to determine using alternative
      technologies. Over the recent few years we and others have developed a range of
      proteomic technologies for the quantitative analysis of microbial proteomes.
      Here, we describe the most commonly used techniques and discuss their strengths
      and weaknesses and illustrate their respective performance for the identification
      of virulence factors in Streptococcus pyogenes.

PMID- 21726055
TI  - Novel silicon-containing analogues of the retinoid agonist bexarotene: syntheses
      and biological effects on human pluripotent stem cells.
AB  - Twofold sila-substitution (C/Si exchange) of the clinically used RXR-selective
      retinoid agonist bexarotene leads to disila-bexarotene, which displays
      pharmacological potency similar to that of the parent carbon compound, as shown
      in a HeLa-cell-based RXR assay. Formal exchange of the SiCH2CH2 Si group in
      disila-bexarotene with a SiCH2Si or SiOSi moiety leads to the disila-bexarotene
      analogues 8 and 9. The silicon compounds 8 and 9 were synthesized in multistep
      syntheses, starting from HC=C(CH3)2SiCH2Si(CH3)2C=CH and
      HC=C(CH3)2SiOSi(CH3)2C=CH, respectively. The key step in the syntheses of 8 and 9
      is a cobalt-catalyzed [2+2+2] cycloaddition reaction that affords the 1,3
      disilaindane and 2-oxa-1,3-disilaindane skeletons. Disila-bexarotene and its
      analogues 8 and 9 were studied for their biological effects relative to all-trans
      retinoic acid in cultured human pluripotent stem cells. The parent carbon
      compound bexarotene was included in some of these biological studies. Although
      the silicon-containing bexarotene analogues disila-bexarotene, 8, and 9 appear
      not to regulate the differentiation of TERA2.cl.SP12 stem cells, preliminary
      evidence indicates that these compounds may possess enhanced functions over the
      parent compound bexarotene, such as induction and regulation of cell death and
      cell numbers. The biological data obtained indicate that bexarotene, contrary to
      the silicon-containing analogues disila-bexarotene, 8, and 9, may partially act
      to induce cell differentiation.

PMID- 21726056
TI  - Two-photon-absorption technique for selective detection of copper(II) ions in
      aqueous solution using a dansyl-pyrene conjugate.

PMID- 21726057
TI  - Proteomic analysis of seed germination under salt stress in soybeans.
AB  - Soybean (Glycine max (L.) Merrill) is a salt-sensitive crop, and its production
      is severely affected by saline soils. Therefore, the response of soybean seeds to
      salt stress during germination was investigated at both physiological and
      proteomic levels. The salt-tolerant cultivar Lee68 and salt-sensitive cultivar
      N2899 were exposed to 100 mmol/L NaCl until radicle protrusion from the seed
      coat. In both cultivars, the final germination percentage was not affected by
      salt, but the mean germination times of Lee68 and N2899 were delayed by 0.3 and
      1.0 d, respectively, compared with controls. In response to salt stress, the
      abscisic acid content increased, and gibberellic acid (GA1+3) and
      isopentenyladenosine decreased. Indole-3-acetic acid increased in Lee68, but
      remained unchanged in N2899. The proteins extracted from germinated seeds were
      separated using two-dimensional gel electrophoresis (2-DE), followed by Coomassie
      brilliant blue G-250 staining. About 350 protein spots from 2-DE gels of pH range
      3 to 10 and 650 spots from gels of pH range 4 to 7 were reproducibly resolved, of
      which 18 protein spots showed changes in abundance as a result of salt stress in
      both cultivars. After matrix-assisted laser desorption ionization-time of flight
      mass spectroscopy (MALDI-TOF-MS) analysis of the differentially expressed
      proteins, the peptide mass fingerprint was searched against the soybean UniGene
      database and nine proteins were successfully identified. Ferritin and 20S
      proteasome subunit beta-6 were up-regulated in both cultivars. Glyceraldehyde 3
      phosphate dehydrogenase, glutathione S-transferase (GST) 9, GST 10, and seed
      maturation protein PM36 were down-regulated in Lee68 by salt, but still remained
      at a certain level. However, these proteins were present in lower levels in
      control N2899 and were up-regulated under salt stress. The results indicate that
      these proteins might have important roles in defense mechanisms against salt
      stress during soybean seed germination.

PMID- 21726058
TI  - Mapping of quantitative trait loci for fiber and lignin contents from an
      interspecific cross Oryza sativa*Oryza rufipogon.
AB  - Rice straw is always regarded as a by-product of rice production, but it could be
      a significant energy source for ruminant animals. Knowledge of the genetic
      variation and genetic architecture of cell wall traits will facilitate rice
      breeders by improving relevant traits through selective breeding and genetic
      engineering. The common wild rice, Oryza rufipogon Griff., which is considered to
      be the progenitor of Oryza sativa, has been widely utilized for the
      identification of genes of agronomic importance for rice genetic improvement. In
      the present study, the mapping of quantitative trait loci (QTLs) for acid
      detergent fiber (ADF), neutral detergent fiber (NDF), acid detergent lignin
      (ADL), and ADL/NDF ratio was carried out in two environments using a backcrossed
      inbred line (BIL) population derived from a cross between the recurrent parent
      Xieqingzao B (XB) and an accession of Dongxiang wild rice (DWR). The results
      indicated that all four traits tested were continuously distributed among the
      BILs, but many BILs showed transgressive segregation. A total of 16 QTLs were
      identified for the four traits, but no QTLs were in common in two environments,
      suggesting that environment has dramatic effects on fiber and lignin syntheses.
      Compared to the QTL positions for grain yield-related traits, there were no
      unfavorable correlations between grain yield components and cell wall traits in
      this population. The QTLs identified in this study are useful for the development
      of dual-purpose rice varieties that are high in grain yield and are also high in
      straw quality.

PMID- 21726059
TI  - Construction and detection of expression vectors of microRNA-9a in BmN cells.
AB  - MicroRNAs (miRNAs) are small endogenous RNAs molecules, approximately 21-23
      nucleotides in length, which regulate gene expression by base-pairing with 3'
      untranslated regions (UTRs) of target mRNAs. However, the functions of only a few
      miRNAs in organisms are known. Recently, the expression vector of artificial
      miRNA has become a promising tool for gene function studies. Here, a method for
      easy and rapid construction of eukaryotic miRNA expression vector was described.
      The cytoplasmic actin 3 (A3) promoter and flanked sequences of miRNA-9a (miR-9a)
      precursor were amplified from genomic DNA of the silkworm (Bombyx mori) and was
      inserted into pCDNA3.0 vector to construct a recombinant plasmid. The enhanced
      green fluorescent protein (EGFP) gene was used as reporter gene. The Bombyx mori
      N (BmN) cells were transfected with recombinant miR-9a expression plasmid and
      were harvested 48 h post transfection. Total RNAs of BmN cells transfected with
      recombinant vectors were extracted and the expression of miR-9a was evaluated by
      reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot. Tests
      showed that the recombinant miR-9a vector was successfully constructed and the
      expression of miR-9a with EGFP was detected.

PMID- 21726060
TI  - Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits
      antimetastatic activity via the inhibition of NF-kappaB-dependent MMP-9 and VEGF
      expressions.
AB  - Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from
      the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations
      were conducted on the effects of DSEA on tumor cell adhesion, migration,
      invasion, and angiogenesis. In this study, we found that DSEA inhibited the
      proliferation of human hepatocellular liver carcinoma cells Hep G2, with a half
      maximal inhibitory concentration (IC50) of 2.65 MUmol/L, and suppressed Hep G2
      cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also
      reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro
      and attenuated neovascularization in the chick embryo chorioallantoic membrane
      (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly
      decreased the expression of matrix metalloproteinase-9 (MMP-9), which plays an
      important role in the degradation of basement membrane in tumor metastasis and
      angiogenesis. DSEA also increased the protein expression level of tissue
      inhibitor of metalloproteinase-1 (TIMP-1), an important regulator of MMP-9
      activation. From the results of Western blotting, the expressions of nuclear
      factor-kappa B (NF-kappaB) and vascular endothelial growth factor (VEGF) were
      found to be remarkably reduced by DSEA. These findings suggest that DSEA exhibits
      a significant anti-metastatic activity through the specific inhibition of NF
      kappaB-dependent MMP-9 and VEGF expressions.

PMID- 21726061
TI  - Construction of the yeast whole-cell Rhizopus oryzae lipase biocatalyst with high
      activity.
AB  - Surface display is effectively utilized to construct a whole-cell biocatalyst.
      Codon optimization has been proven to be effective in maximizing production of
      heterologous proteins in yeast. Here, the cDNA sequence of Rhizopus oryzae lipase
      (ROL) was optimized and synthesized according to the codon bias of Saccharomyces
      cerevisiae, and based on the Saccharomyces cerevisiae cell surface display system
      with alpha-agglutinin as an anchor, recombinant yeast displaying fully codon
      optimized ROL with high activity was successfully constructed. Compared with the
      wild-type ROL-displaying yeast, the activity of the codon-optimized ROL yeast
      whole-cell biocatalyst (25 U/g dried cells) was 12.8-fold higher in a hydrolysis
      reaction using p-nitrophenyl palmitate (pNPP) as the substrate. To our knowledge,
      this was the first attempt to combine the techniques of yeast surface display and
      codon optimization for whole-cell biocatalyst construction. Consequently, the
      yeast whole-cell ROL biocatalyst was constructed with high activity. The optimum
      pH and temperature for the yeast whole-cell ROL biocatalyst were pH 7.0 and 40 
      degrees C. Furthermore, this whole-cell biocatalyst was applied to the hydrolysis
      of tributyrin and the resulted conversion of butyric acid reached 96.91% after
      144 h.

PMID- 21726062
TI  - Influence of surface roughness on the color of dental-resin composites.
AB  - This study deals with the influence of surface roughness on the color of resin
      composites. Ten resin composites (microfilled, hybrid, and microhybrid) were each
      polished with 500-grit, 1200-grit, 2000-grit, and 4000-grit SiC papers. The
      roughness parameter (R(a)) was measured using a PlMU confocal microscope, and
      field-emission scanning electron microscope (Fe-SEM) images were used to
      investigate filler morphology. Color was measured using a spectroradiometer and a
      D65 standard illuminant (geometry diffuse/0 degrees  specular component excluded
      (SCE) mode). Surface roughness decreased with grit number and was not influenced
      by filler size or size distribution. A significant influence of R(a) on lightness
      (L*) was found. Lightness increased with decreases in roughness, except for
      specimens that underwent polishing procedure 4 (PP4; 500-grit, 1200-grit, 2000
      grit, and 4000-grit SiC papers consecutively). Generally, it was found that
      surface roughness influenced the color of resin composites. The composites that
      underwent PP1 (500-grit SiC paper) exhibited significant differences in chroma
      (C*), hue (h degrees ), and lightness (L*) compared to composites that underwent
      PP3 (500-grit, 1200-grit, and 2000-grit SiC papers consecutively) and PP4. Color
      difference (?E*) between the polishing procedures was within acceptability
      thresholds in dentistry.

PMID- 21726063
TI  - Microcalorimetry studies on the antibacterial effect of crude monkshood
      polysaccharide.
AB  - In this paper, crude monkshood polysaccharide was isolated from Radix Aconiti
      Lateralis Preparata. The effects of crude monkshood polysaccharide on Escherichia
      coli and Staphylococcus aureus were investigated by microcalorimetry. The power
      time curves of the bacterial growth at various concentrations (c) of crude
      monkshood polysaccharide were plotted with a TAM air isothermal microcalorimeter
      at 37  degrees C. The growth rate constant (MU), inhibitory ratio (I), peak
      height (P(m)), and peak-time (t(m)) were calculated. From the data, the
      relationship between MU and c also was established. The growth rate constant MU
      decreased with the increasing concentrations of crude monkshood polysaccharide.
      Moreover, P(m) reduced and t(m) increased with increasing concentrations. The
      experimental results revealed that crude monkshood polysaccharide had inhibitory
      activity towards S. aureus and E. coli. Results obtained from our study strongly
      suggest that microcalorimetry is a fast, simple, and more sensitive technology
      that can be easily performed to study the effect of drugs on bacteria.

PMID- 21726064
TI  - Berbamine inhibits proliferation and induces apoptosis of KU812 cells by
      increasing Smad3 activity.
AB  - OBJECTIVE: The cytotoxic effect of berbamine on chronic myeloid leukemia (CML)
      cell line KU812 was evaluated, and the mechanisms of its action were explored.
      METHODS: The effect of berbamine on the KU812 cell growth was determined by
      methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry was used to profile cell
      cycle alteration upon berbamine treatment. Reverse transcription polymerase chain
      reaction (RT-PCR) was carried out to determine the transcripts of transforming
      growth factor-beta (TGF-beta) receptors (TbetaRs), Smad3, c-Myc, cyclin D1,
      p21(Cip1)(p21), and p27(Kip1)(p27). Changes in the protein levels of total Smad3,
      phosphorylated Smad3, the downstream targets of Smad3, and specific apoptosis
      related factors were evaluated by Western blotting. RESULTS: Berbamine inhibited
      KU812 cell proliferation in a dose- and time-dependent manner, and the half
      maximal inhibitory concentration (IC50) values for treatments of 24, 48, and 72 h
      were 5.83, 3.43, and 0.75 MUg/ml, respectively. Berbamine induced G1 arrest as
      well as apoptosis in KU812 cells. Transcriptions of Smad3 and p21 were up
      regulated, while those of TbetaRI, TbetaRII, c-Myc, cyclin D1 and p27 were not
      changed significantly. The protein levels of both total Smad3 and phosphorylated
      Smad3 were both up-regulated after berbamine treatment, together with decreased c
      Myc and cyclin D1 and increased p21. Meanwhile, the levels of the anti-apoptotic
      proteins, such as Bcl-2 and Bcl-xL, were decreased, whereas pro-apoptotic Bax was
      increased. CONCLUSIONS: Berbamine suppresses KU812 cell proliferation through
      induction of cell cycle arrest in G1 and apoptosis. It activates Smad3 without
      additional stimulation of TGF-beta, and alters the levels of the Smad3 downstream
      targets, including c-Myc, cyclin D1 and p21. Our findings suggest that berbamine
      is a promising drug in the treatment of advanced stage patients with CML.

PMID- 21726065
TI  - Unilateral hemilaminectomy for patients with intradural extramedullary tumors.
AB  - A modified hemilaminectomy was introduced in an attempt to explore the operative
      techniques and the values of the limited approach to spinal cord tumors. Forty
      five consecutive patients with intradural extramedullary lesions, who underwent
      modified hemilaminectomy, were studied retrospectively. The intraspinal tumors
      were removed via the limited bone window with a 3.3-cm mean length (range: 2.0
      6.5 cm) and a 1.2-cm mean width (range: 0.6-1.5 cm), in which the inner parts of
      the medial and lateral laminae were mostly undercut for wider view. Spinal
      lesions were cervical in 21 cases, thoracic in 12 cases, lumbar in 10 cases, and
      multiple in 2 cases. Forty-three cases were completely excised via
      hemilaminectomy alone. Two subjects with dumbbell neurinoma underwent two-stage
      tumor removal via anterolateral cervical approach following hemilaminectomy. With
      respect to neurological status, the percentage of good Frankel scale (D+E grade)
      was markedly improved from 22.2% on admission to 93.3% at follow-up. At the
      median 26-month follow-up evaluation by magnetic resonance imaging (MRI), none of
      the subjects showed spinal deformity or instability. By preserving
      musculoligamentous attachments and posterior bony elements as much as possible,
      the modified approach is minimally invasive and may be routinely used to remove
      intradural and extramedullary tumors, especially in patients with meningiomas and
      neurinomas.

PMID- 21726066
TI  - Osteoinduction by Ca-P biomaterials implanted into the muscles of mice.
AB  - The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been
      widely reported and documented, but little research has been performed on rodent
      animals, e.g., mice. In this study, we report osteoinduction in a mouse model.
      Thirty mice were divided into two groups. BCP materials (Sample A) and control
      ceramics (Sample B) were implanted into the leg muscle, respectively. Five mice
      in each group were killed at 15, 30, and 45 d after surgery. Sample A and Sample
      B were harvested and used for hematoxylin and eosin (HE) staining,
      immunohistochemistry (IHC) staining, and Alizarin Red S staining to check bone
      formation in the biomaterials. Histological analysis showed that no bone tissue
      was formed 15 d after implantation (0/5) in either of the two groups. Newly
      formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after
      implantation; the average amounts of newly-formed bone tissues were approximately
      5.2% and 8.6%, respectively. However, we did not see any bone tissue in Sample B
      until 45 d after implantation. Bone-related molecular makers such as bone
      morphogenesis protein-2 (BMP-2), collagen type I, and osteopontin were detected
      by IHC staining in Sample A 30 d after implantation. In addition, the newly
      formed bone was also confirmed by Alizarin Red S staining. Because this is the
      report of osteoinduction in the rodent animal on which all the biotechnologies
      were available, our results may contribute to further mechanism research.

PMID- 21726067
TI  - Dilemma of concepts and strategies for the prevention of spread of HIV in
      relation to human behavior, law and human rights.
AB  - The new prevalence data regarding the estimated global number of human
      immunodeficiency virus positive (HIV+) cases, i.e., including people who are
      either aware or unaware of their HIV infection in 2010, lead many to wonder why
      the increase in incidence has reached today's unprecedented level and escalated
      within such a short time. This, in spite of prevention campaigns in countries
      affected by HIV/acquired immune deficiency syndrome (AIDS) with their urgent
      messages aimed at preventing HIV transmission by promoting changes in
      individual's behavior. This article analyzes the background of the prevention
      strategies, in particular their political, social and legal concepts in terms of
      human rights, and reveals traits of human behavior not considered thus far. A
      radical reappraisal is necessary, at social and legislative levels, as well as
      options additional to current concepts. When ethical issues come up, they become
      blamed for outmoded moralistic positions. However, ignoring the reality has led
      to dire consequences from prioritizing individual human rights over society's
      collective need to prevent the spread of HIV.

PMID- 21726068
TI  - The cardiac sodium channel is post-translationally modified by arginine
      methylation.
AB  - The alpha subunit of the cardiac sodium channel (Na(v)1.5) is an essential
      protein in the initial depolarization phase of the cardiomyocyte action
      potential. Post-translational modifications such as phosphorylation are known to
      regulate Na(v)1.5 function. Here, we used a proteomic approach for the study of
      the post-translational modifications of Na(v)1.5 using tsA201 cells as a model
      system. We generated a stable cell line expressing Na(v)1.5, purified the sodium
      channel, and analyzed Na(v)1.5 by MALDI-TOF and LC-MS/MS. We report the
      identification of arginine methylation as a novel post-translational modification
      of Na(v)1.5. R513, R526, and R680, located in the linker between domains I and II
      in Na(v)1.5, were found in mono- or dimethylated states. The functional relevance
      of arginine methylation in Na(v)1.5 is underscored by the fact that R526H and
      R680H are known Na(v)1.5 mutations causing Brugada and long QT type 3 syndromes,
      respectively. Our work describes for the first time arginine methylation in the
      voltage-gated ion channel superfamily.

PMID- 21726069
TI  - Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as
      potential anticancer immunomodulators.
AB  - Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an
      important mechanism of peripheral immune tolerance contributing to tumoral immune
      resistance. IDO inhibition is thus an active area of research in drug
      development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO),
      an unrelated hepatic enzyme also catalyzing the first step of tryptophan
      degradation, is also expressed in many tumors and that this expression prevents
      tumor rejection by locally depleting tryptophan. Herein, we report a structure
      activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel
      derivatives were synthesized, and their TDO inhibitory potency was evaluated. The
      rationalization of the structure-activity relationships (SARs) revealed essential
      features to attain high TDO inhibition and notably a dense H-bond network mainly
      involving His(55) and Thr(254) residues. Our study led to the identification of a
      very promising compound (58) displaying good TDO inhibition (K(i) = 5.5 MUM),
      high selectivity, and good oral bioavailability. Indeed, 58 was chosen for
      preclinical evaluation.

PMID- 21726070
TI  - Effect of pH, NaCl, CaCl2 and temperature on self-assembly of beta-lactoglobulin
      into nanofibrils: a central composite design study.
AB  - The ability of certain globular proteins to self-assemble into amyloid-like
      fibrils in vitro opens opportunities for the development of new biomaterials with
      unique functional properties, like highly efficient gelation and viscosity
      enhancement. This work explored the individual and interacting effects of pH (1
      to 3), NaCl (0-100 mM), CaCl(2) (0-80 mM) and heating temperature (80 to 120 
      degrees C) on the kinetics of beta-lactoglobulin self-assembly and the morphology
      of resulting nanofibrils. Statistically significant (p < 0.05) interactions
      included CaCl(2)*temperature, NaCl*pH, CaCl(2)*pH, temperature*pH and
      NaCl*CaCl(2). Particularly notable was the very rapid self-assembly at pH 3 and
      the highly nonlinear effect of pH on self-assembly kinetics. Nanofibril
      morphologies ranged from long and semiflexible or curled and twisted to short and
      irregular. There did not seem to be a link between the kinetics of fibril
      formation and the morphology of fibrils, except at pH 3, where self-assembly was
      very rapid and fibrils were short and irregular, suggesting haphazard,
      uncontrolled self-assembly.

PMID- 21726071
TI  - Scanning tunneling microscopy and X-ray photoelectron spectroscopy studies of
      graphene films prepared by sonication-assisted dispersion.
AB  - We describe scanning tunneling microscopy and X-ray photoelectron spectroscopy
      studies of graphene films produced by sonication-assisted dispersion. Defects in
      these samples are not randomly distributed, and the graphene films exhibit a
      "patchwork" structure where unperturbed graphene areas are adjacent to heavily
      functionalized ones. Adjacent graphene layers are likely in poor mechanical
      contact due to adventitious species trapped between the carbon sheets of the
      sample.

PMID- 21726072
TI  - Dynamic and reversible control of 2D membrane protein concentration in a droplet
      interface bilayer.
AB  - We form an artificial lipid bilayer between a nanolitre aqueous droplet and a
      supporting hydrogel immersed in an oil/lipid solution. Manipulation of the axial
      position of the droplet relative to the hydrogel controls the size of the bilayer
      formed at the interface; this enables the surface density of integral membrane
      proteins to be controlled. We are able to modulate the surface density of the
      beta-barrel pore-forming toxin alpha-hemolysin over a range of 4 orders of
      magnitude within a time frame of a few seconds. The concentration changes are
      fully reversible. Membrane protein function and diffusion are unaltered, as
      measured by single molecule microscopy and single channel electrical recording.

PMID- 21726073
TI  - Large-scale protein profiling in human cell lines using antibody-based
      proteomics.
AB  - Human cancer cell lines grown in vitro are frequently used to decipher basic cell
      biological phenomena and to also specifically study different forms of cancer.
      Here we present the first large-scale study of protein expression patterns in
      cell lines using an antibody-based proteomics approach. We analyzed the
      expression pattern of 5436 proteins in 45 different cell lines using hierarchical
      clustering, principal component analysis, and two-group comparisons for the
      identification of differentially expressed proteins. Our results show that
      immunohistochemically determined protein profiles can categorize cell lines into
      groups that overall reflect the tumor tissue of origin and that hematological
      cell lines appear to retain their protein profiles to a higher degree than cell
      lines established from solid tumors. The two-group comparisons reveal well
      characterized proteins as well as previously unstudied proteins that could be of
      potential interest for further investigations. Moreover, multiple myeloma cells
      and cells of myeloid origin were found to share a protein profile, relative to
      the protein profile of lymphoid leukemia and lymphoma cells, possibly reflecting
      their common dependency of bone marrow microenvironment. This work also provides
      an extensive list of antibodies, for which high-resolution images as well as
      validation data are available on the Human Protein Atlas ( www.proteinatlas.org
      ), that are of potential use in cell line studies.

PMID- 21726074
TI  - Validation of peptide MS/MS spectra using metabolic isotope labeling for spectral
      matching-based shotgun proteome analysis.
AB  - We report an isotope labeling shotgun proteome analysis strategy to validate the
      spectrum-to-sequence assignments generated by using sequence-database searching
      for the construction of a more reliable MS/MS spectral library. This strategy is
      demonstrated in the analysis of the E. coli K12 proteome. In the workflow, E.
      coli cells were cultured in normal and (15)N-enriched media. The differentially
      labeled proteins from the cell extracts were subjected to trypsin digestion and
      two-dimensional liquid chromatography quadrupole time-of-flight tandem mass
      spectrometry (2D-LC QTOF MS/MS) analysis. The MS/MS spectra of the two samples
      were individually searched using Mascot against the E. coli proteome database to
      generate lists of peptide sequence matches. The two data sets were compared by
      overlaying the spectra of unlabeled and labeled matches of the same peptide
      sequence for validation. Two cutoff filters, one based on the number of common
      fragment ions and another one on the similarity of intensity patterns among the
      common ions, were developed and applied to the overlaid spectral pairs to reject
      the low quality or incorrectly assigned spectra. By examining 257,907 and 245,156
      spectra acquired from the unlabeled and (15)N-labeled samples, respectively, an
      experimentally validated MS/MS spectral library of tryptic peptides was
      constructed for E. coli K12 that consisted of 9,302 unique spectra with unique
      sequence and charge state, representing 7,763 unique peptide sequences. This E.
      coli spectral library could be readily expanded, and the overall strategy should
      be applicable to other organisms. Even with this relatively small library, it was
      shown that more peptides could be identified with higher confidence using the
      spectral search method than by sequence-database searching.

PMID- 21726075
TI  - Sex-biased protein expression in threespine stickleback, Gasterosteus aculeatus.
AB  - In the threespine stickleback, males and females are sexually dimorphic, having
      slight differences in body morphology but pronounced differences in reproductive
      behaviors and phenotype during the mating season. Recent interest in sex
      chromosome evolution and sex-specific gene expression has surged toward
      understanding the molecular basis of sexual dimorphism in this species. Sex
      biased gene expression at the transcriptome level in liver tissue of
      nonreproductively active fish was reported recently, yet proteome level
      investigations in the species are scarce. Thus, proteome level investigations
      will supplement ongoing genomic studies in threespine stickleback. In this study,
      protein expression in liver was compared between the sexes using label-free
      quantitation. Over 300 proteins with a 95% confidence level were identified from
      fish that were not reproductively active. Common functions included metabolism
      related to amino acids and lipids and energy metabolism characteristic of normal
      liver function. Of the identified proteins, 5.8% were differentially expressed
      between the sexes. Male-biased genes had functions related to amino acid
      metabolism and signaling whereas female-biased genes were related to protein
      synthesis.

PMID- 21726076
TI  - Improving SRM assay development: a global comparison between triple quadrupole,
      ion trap, and higher energy CID peptide fragmentation spectra.
AB  - In proteomics, selected reaction monitoring (SRM) is rapidly gaining importance
      for targeted protein quantification. The triple quadrupole mass analyzers used in
      SRM assays allow for levels of specificity and sensitivity hard to accomplish by
      more standard shotgun proteomics experiments. Often, an SRM assay is built by in
      silico prediction of transitions and/or extraction of peptide precursor and
      fragment ions from a spectral library. Spectral libraries are typically generated
      from nonideal ion trap based shotgun proteomics experiments or synthetic peptide
      libraries, consuming considerable time and effort. Here, we investigate the
      usability of beam type CID (or "higher energy CID" (HCD)) peptide fragmentation
      spectra, as acquired using an Orbitrap Velos, to facilitate SRM assay
      development. Therefore, peptide fragmentation spectra, obtained by ion-trap CID,
      triple-quadrupole CID (QqQ-CID) and Orbitrap HCD, originating from digested
      cellular lysates, were compared. Spectral comparison and a dedicated correlation
      algorithm indicated significantly higher similarity between QqQ-CID and HCD
      fragmentation spectra than between QqQ-CID and ion trap-CID spectra. SRM
      transitions generated using a constructed HCD spectral library increased SRM
      assay sensitivity up to 2-fold, when compared to the use of a library created
      from more conventionally used ion trap-CID spectra, showing that HCD spectra can
      assist SRM assay development.

PMID- 21726077
TI  - The lipogenesis pathway as a cancer target.

PMID- 21726078
TI  - Detailed electrochemical analysis of the redox chemistry of
      tetrafluorotetracyanoquinodimethane TCNQF4, the radical anion [TCNQF4]*-, and the
      dianion [TCNQF4]2- in the presence of trifluoroacetic acid.
AB  - The electrochemistry of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane
      (TCNQF(4)), [TCNQF(4)](*-), and [TCNQF(4)](2-) have been studied in acetonitrile
      (0.1 M [Bu(4)N][ClO(4)]). Transient and steady-state voltammetric techniques have
      been utilized to monitor the generation of [TCNQF(4)](*-) and [TCNQF(4)](2-)
      anions as well as their reactions with trifluoroacetic acid (TFA). In the absence
      of TFA, the reduction of TCNQF(4) occurs via two, diffusion controlled,
      chemically and electrochemically reversible, one-electron processes where the
      reversible formal potentials are 0.31 and -0.22 V vs Ag/Ag(+). Unlike the TCNQ
      analogues, both [TCNQF(4)](*-) and [TCNQF(4)](2-) are persistent when generated
      via bulk electrolysis even under aerobic conditions. Voltammetric and UV-vis data
      revealed that although the parent TCNQF(4) does not react with TFA, the
      electrochemically generated radical anion and dianion undergo facile protonation
      to yield [HTCNQF(4)](*), [HTCNQF(4)](-) and H(2)TCNQF(4) respectively. The
      voltammetry can be simulated to give a complete thermodynamic and kinetic
      description of the complex, coupled redox and acid-base chemistry. The data
      indicate dramatically different equilibrium and rate constants for the
      protonation of [TCNQF(4)](*-) (K(eq) = 3.9 * 10(-6), k(f) = 1.0 * 10(-3) M(-1) s(
      1)) and [TCNQF(4)](2-) (K(eq) = 3.0 * 10(3), k(f) = 1.0 * 10(10) M(-1) s(-1)) in
      the presence of TFA.

PMID- 21726079
TI  - Effect of organic-phase solvents on physicochemical properties and cellular
      uptake of astaxanthin nanodispersions.
AB  - A simplex centroid mixture design was used to study the interactions between two
      chosen solvents, dichloromethane (DCM) and acetone (ACT), as organic-phase
      components in the formation and physicochemical characterization and cellular
      uptake of astaxanthin nanodispersions produced using precipitation and
      condensation processes. Full cubic or quadratic regression models with acceptable
      determination coefficients were obtained for all of the studied responses.
      Multiple-response optimization predicted that the organic phase with 38% (w/w)
      DCM and 62% (w/w) ACT yielded astaxanthin nanodispersions with the minimum
      particle size (106 nm), polydispersity index (0.191), and total astaxanthin loss
      (12.7%, w/w) and the maximum cellular uptake (2981 fmol/cell). Astaxanthin
      cellular uptake from the produced nanodispersions also showed a good correlation
      with their particle size distributions and astaxanthin trans/cis isomerization
      ratios. The absence of significant (p > 0.05) differences between the
      experimental and predicted values of the response variables confirmed the
      adequacy of the fitted models.

PMID- 21726080
TI  - Structure analysis of an amyloid-forming model peptide by a systematic glycine
      and proline scan.
AB  - The ability to adopt at least two different stable conformations is a common
      feature of proteins involved in many neurodegenerative diseases. The involved
      molecules undergo a conformational transition from native, mainly helical states
      to insoluble amyloid structures that have high beta-sheet content. A detailed
      characterization of the molecular architecture of highly ordered amyloid
      structures, however, is still challenging. Their intrinsically low solubility and
      high tendency to aggregate often considerably limits the application of
      established high-resolution techniques such as NMR and X-ray crystallography. An
      alternative approach to elucidating the tertiary and quaternary organization
      within an amyloid fibril is the systematic replacement of residues with amino
      acids that exhibit special conformational characteristics, such as glycine and
      proline. Substitutions within the beta-sheet-prone sequences of the molecules
      usually severely affect their ability to form fibrils, whereas incorporation at
      external loop- and bend-like positions often has only marginal effects. Here we
      present the characterization of the internal architecture of a de novo designed
      coiled-coil-based amyloid-forming model peptide by means of a series of
      systematic single glycine and proline replacements in combination with a set of
      simple low-resolution methods. The folding and assembly behavior of the
      substituted peptides was monitored simultaneously using circular dichroism
      spectroscopy, Thioflavin T fluorescence staining, and transmission electron
      microscopy. On the basis of the obtained data, we successfully identify
      characteristic bend and core positions within the peptide sequence and propose a
      detailed structural model of the internal fibrillar arrangement.

PMID- 21726081
TI  - Polarization controlled kinetics and composition of trivalent chromium coatings
      on aluminum.
AB  - Combined in situ spectroscopic ellipsometry and electrochemistry have been
      employed to monitor, in real-time, the formation of trivalent Cr conversion
      coatings on polished Al substrates at applied sample potentials. It is found that
      the formation kinetics and chemical composition of the film can be controlled by
      adjusting the anodic and cathodic reactions. The growth kinetics are accelerated
      at more positive anodic potentials or more negative cathodic potentials. At more
      negative potentials, the percentage of chromium in the coating is found to
      increase, while the zirconium percentage decreases.

PMID- 21726082
TI  - Diastereoselective total synthesis of (+)-13-stemarene by fourth generation
      methods: a formal total synthesis of (+)-18-deoxystemarin.
AB  - The problem of constructing diastereoselectively the C/D ring system of stemarane
      diterpenes from a bicyclo[2.2.2]octane intermediate was solved resulting in very
      simple synthesis of (+)-13-stemarene 1. The obtaining of the latter represents
      also a formal synthesis of (+)-18-deoxystemarin 2. In the key step, the epimeric
      mixture 10, dissolved in toluene, was converted by the action of TsOH into (+)
      stemar-13-en-15-one 28.

PMID- 21726083
TI  - Quantitative determination of competitive molecular adsorption on gold
      nanoparticles using attenuated total reflectance-Fourier transform infrared
      spectroscopy.
AB  - Surface-sensitive quantitative studies of competitive molecular adsorption on
      nanoparticles were conducted using a modified attenuated total reflectance
      Fourier transform infrared (ATR-FTIR) spectroscopy method. Adsorption isotherms
      for thiolated poly(ethylene glycol) (SH-PEG) on gold nanoparticles (AuNPs) as a
      function of molecular mass (1, 5, and 20 kDa) were characterized. We find that
      surface density of SH-PEG on AuNPs is inversely proportional to the molecular
      mass (M(m)). Equilibrium binding constants for SH-PEG, obtained using the
      Langmuir adsorption model, show the binding affinity for SH-PEG is proportional
      to M(m). Simultaneous competitive adsorption between mercaptopropionic acid (MPA)
      and 5 kDa SH-PEG (SH-PEG5K) was investigated, and we find that MPA concentration
      is the dominant factor influencing the surface density of both SH-PEG5K and MPA,
      whereas the concentration of SH-PEG5K affects only SH-PEG5K surface density.
      Electrospray differential mobility analysis (ES-DMA) was employed as an
      orthogonal characterization technique. ES-DMA results are consistent with the
      results obtained by ATR-FTIR, confirming our conclusions about the adsorption
      process in this system. Ligand displacement competitive adsorption, where the
      displacing molecular species is added after completion of the ligand surface
      binding, was also interrogated by ATR-FTIR. Results indicate that for SH-PEG
      increasing M(m) yields greater stability on AuNPs when measured against
      displacement by bovine serum albumin (BSA) as a model serum protein. In addition,
      the binding affinity of BSA to AuNPs is inhibited for SH-PEG conjugated AuNPs, an
      effect that is enhanced at higher SH-PEG M(m) values.

PMID- 21726084
TI  - Inactivation of MS2 coliphage by ferrous ion and zero-valent iron nanoparticles.
AB  - This study demonstrates the inactivation of MS2 coliphage (MS2) by nano
      particulate zerovalent iron (nZVI) and ferrous ion (Fe[II]) in aqueous solution.
      For nZVI, the inactivation efficiency of MS2 under air-saturated conditions was
      greater than that observed under deaerated conditions, indicating that reactions
      associated with the oxidation of nZVI were mainly responsible for the MS2
      inactivation. Under air-saturated conditions, the inactivation efficiency
      increased with decreasing pH for both nZVI and Fe(II), associated with the pH
      dependent stability of Fe(II). Although the Fe(II) released from nZVI appeared to
      contribute significantly to the virucidal activity of nZVI, several findings
      suggest that the nZVI surfaces interacted directly with the MS2 phages, leading
      to their inactivation. First, the addition of 1,10-phenanthroline (a strong
      Fe(II)-chelating agent) failed to completely block the inactivation of MS2 by
      nZVI. Second, under deaerated conditions, a linear dose-log inactivation curve
      was still observed for nZVI. Finally, ELISA analysis indicated that nZVI caused
      more capsid damage than Fe(II).

PMID- 21726085
TI  - Potential fungal inhibition by immobilized hydrolytic enzymes from Trichoderma
      asperellum.
AB  - The use of cell wall degrading enzymes from Trichoderma asperellum immobilized on
      biodegradable support is an alternative for food packaging. In this study,
      hydrolytic enzymes produced by T. asperellum were tested as a fungal growth
      inhibitor, in free form or immobilized on a biodegradable film composed of
      cassava starch and poly(butylene adipate-co-terephtalate) (PBAT). The inhibitory
      activity was tested against Aspergillus niger , Penicillium sp., and Sclerotinia
      sclerotiorum , microorganisms that frequently degrade food packaging. The use of
      chitin as carbon source in liquid medium induced T. asperellun to produce N
      acetylglucosaminidase, beta-1,3-glucanase, chitinase, and protease. The presence
      of T. asperellun cell wall degradating enzymes (T-CWD) immobilized by adsorption
      or covalent attachment resulted in effective inhibition of fungal growth. The
      enzymatic activity of T-CWD was stronger on S. sclerotiorum than on the
      Aspergillus or Penicillum isolates tested. These results suggest that T-CWD can
      be used in a free or immobilized form to suppress fungi that degrade food
      packaging.

PMID- 21726086
TI  - Analytical study of azadirachtin and 3-tigloylazadirachtol residues in foliage
      and phloem of hardwood tree species by liquid chromatography-electrospray mass
      spectrometry.
AB  - A rapid and sensitive LC-ESI-MS method has been developed and validated for the
      quantitation of azadirachtin and 3-tigloylazadirachtol in deciduous tree
      matrices. The method involves automated extraction and simultaneous cleanup using
      an accelerated solvent technique with the matrix dispersed in solid phase over a
      layer of primary-secondary amine silica. The limits of quantification were 0.02
      mg/kg for all matrices with the exception of Norway maple foliage (0.05 mg/kg).
      Validation at three levels (0.02, 0.1, and 1 mg/kg), demonstrated satisfactory
      recoveries (71-103%) with relative standard deviation <20%. Two in-source
      fragment ions were used for confirmation at levels above 0.1 mg/kg. Over a period
      of several months, quality control analyses showed the technique to be robust and
      effective in tracking the fate of these natural botanical insecticides following
      systemic injection into various tree species for control of invasive insect pest
      species such as the emerald ash borer and Asian longhorned beetle.

PMID- 21726087
TI  - Structure and function of the oxidation products of polyphenols and
      identification of potent lipoxygenase inhibitors from Fe-catalyzed oxidation of
      resveratrol.
AB  - Polyphenols have recently attracted much attention as potent antioxidants and
      related bioactive substances. These potent antioxidative polyphenols are very
      oxidizable due to their chemical properties, and their oxidation products must
      accumulate in the oxidizing foods when they are contained as the active
      ingredients. In this investigation, 30 polyphenols and related phenolics were
      oxidized with oxygen in the presence of a catalytic amount of Fe ions.
      Piceatannol, catechin, epicatechin, hydroxytyrosol, carnosol, and carnosic acid
      were oxidized very quickly. Sinapic acid, caffeic acid, chlorogenic acid,
      rosmarinic acid, gallic acid, propyl gallate, alpha-tocopherol, quercetin, and
      nordihydroguaiaretic acid were moderately oxidized. Protocatechuic acid, syringic
      acid, taxifolin, resveratrol, gentisic acid, secoisolariciresinol, and ellagic
      acid were oxidized for 19-20 days; however, their oxidation was very slow and did
      not complete. The other phenolics were not oxidized. The obtained oxidation
      products were next subjected to a lipoxygenase inhibition assay and the results
      compared to those of the corresponding phenols. Very interestingly, the oxidation
      product from resveratrol showed a high inhibitory activity, whereas resveratrol
      itself had no activity and its oxidation efficiency was low. To clarify the
      inhibition principle of the oxidation product, an LC-MS analysis was carried out
      on the oxidation product. The analytical results showed that they are the
      oligomeric and degraded compounds of resveratrol. Among them, the structures of
      three dimeric compounds were successfully identified, and their activity data
      clarified that the closed ring dimers were potent lipoxygenase inhibitors,
      whereas the opened ring dimer was not. It should be noted that resveratrol had
      almost no lipoxygenase inhibitory activity, contrary to some researchers'
      findings.

PMID- 21726088
TI  - Rapid verification of candidate serological biomarkers using gel-based, label
      free multiple reaction monitoring.
AB  - Stable isotope dilution-multiple reaction monitoring-mass spectrometry (SID-MRM
      MS) has emerged as a promising platform for verification of serological candidate
      biomarkers. However, cost and time needed to synthesize and evaluate stable
      isotope peptides, optimize spike-in assays, and generate standard curves quickly
      becomes unattractive when testing many candidate biomarkers. In this study, we
      demonstrate that label-free multiplexed MRM-MS coupled with major protein
      depletion and 1D gel separation is a time-efficient, cost-effective initial
      biomarker verification strategy requiring less than 100 MUL of serum.
      Furthermore, SDS gel fractionation can resolve different molecular weight forms
      of targeted proteins with potential diagnostic value. Because fractionation is at
      the protein level, consistency of peptide quantitation profiles across fractions
      permits rapid detection of quantitation problems for specific peptides from a
      given protein. Despite the lack of internal standards, the entire workflow can be
      highly reproducible, and long-term reproducibility of relative protein abundance
      can be obtained using different mass spectrometers and LC methods with external
      reference standards. Quantitation down to ~200 pg/mL could be achieved using this
      workflow. Hence, the label-free GeLC-MRM workflow enables rapid, sensitive, and
      economical initial screening of large numbers of candidate biomarkers prior to
      setting up SID-MRM assays or immunoassays for the most promising candidate
      biomarkers.

PMID- 21726089
TI  - Residue potential of norsesquiterpene glycosides in tissues of cattle fed Austral
      bracken (Pteridium esculentum).
AB  - Austral bracken, Pteridium esculentum , occurs widely in Australian grazing lands
      and contains both the known carcinogen ptaquiloside and its hydroxy analogue,
      ptesculentoside, with untested carcinogenic potential. Calves were fed a diet
      containing 19% P. esculentum that delivered 1.8 mg of ptaquiloside and 4.0 mg of
      ptesculentoside per kilogram of body weight (bw) per day to explore the carcass
      residue potential of these compounds. Concentrations of ptaquiloside and
      ptesculentoside in the liver, kidney, skeletal muscle, heart, and blood of these
      calves were determined as their respective elimination products, pterosin B and
      pterosin G, by HPLC-UV analysis. Plasma concentrations of up to 0.97 MUg/mL
      ptaquiloside and 1.30 MUg/mL ptesculentoside were found, but were shown to
      deplete to <10% of these values within 24 h of bracken consumption. Both
      glycosides were also detected in all tissues assayed, with ptesculentoside
      appearing to be more residual than ptaquiloside. Up to 0.42 and 0.32 MUg/g
      ptesculentoside was present in skeletal muscle and liver, respectively, 15 days
      after bracken consumption ended. This detection of residual glycosides in tissues
      of cattle feeding on Austral bracken raises health concerns for consumers and
      warrants further investigation.

PMID- 21726090
TI  - Galactose-decorated cross-linked biodegradable poly(ethylene glycol)-b
      poly(epsilon-caprolactone) block copolymer micelles for enhanced hepatoma
      targeting delivery of paclitaxel.
AB  - The inferior in vivo stability of micellar drugs has been a prime challenge for
      their application in targeted drug delivery. Here we report on novel galactose
      decorated covalently cross-linked biodegradable micelles based on photo-cross
      linkable poly(ethylene glycol)-b-poly(acryloyl carbonate)-b-poly(epsilon
      caprolactone) (PEG-PAC-PCL) and galactose-conjugated PEG-PCL (Gal-PEG-PCL)
      copolymers for enhanced hepatoma-targeting delivery of paclitaxel (PTX). The
      molecular weight of PEG in Gal-PEG-PCL was higher than that in PEG-PAC-PCL,
      thereby fully exposing Gal ligands at the micellar surface. These micelles,
      either with or without loading of PTX, were readily cross-linked by UV
      irradiation to afford micelles with small sizes (ca. 79-94 nm) and enhanced
      stability. The in vitro release studies confirmed that drug release from cross
      linked micelles was significantly inhibited. Interestingly, MTT assays showed
      that Gal-decorated PTX-loaded cross-linked micelles retained a high antitumor
      activity in HepG2 cells, which was much more effective than PTX-loaded cross
      linked micelles without Gal ligands and comparable to Gal-decorated PTX-loaded
      non-cross-linked micelles. Remarkably, the preliminary in vivo antitumor efficacy
      studies in SMMC-7721 tumor (human hepatoma)-bearing nude mice revealed that Gal
      decorated PTX-loaded cross-linked micelles inhibited the growth of the human
      hepatoma more effectively than PTX-loaded cross-linked micelles as well as Gal
      decorated PTX-loaded non-cross-linked micelles. These results indicate that Gal
      decorated cross-linked PEG-PCL micelles have great potential in liver tumor
      targeted chemotherapy.

PMID- 21726091
TI  - Exploitation of nano alumina for the chromatographic separation of clinical grade
      188Re from 188W: a renaissance of the 188W/188Re generator technology.
AB  - The (188)W/(188)Re generator using an acidic alumina column for chromatographic
      separation of (188)Re has remained the most popular procedure world over. The
      capacity of bulk alumina for taking up tungstate ions is limited (~50 mg W/g)
      necessitating the use of very high specific activity (188)W (185-370 GBq/g),
      which can be produced only in very few high flux reactors available in the world.
      In this context, the use of high-capacity sorbents would not only mitigate the
      requirement of high specific activity (188)W but also facilitate easy access to
      (188)Re. A solid state mechanochemical approach to synthesize nanocrystalline
      gamma-Al(2)O(3) possessing very high W-sorption capacity (500 mg W/g) was
      developed. The structural and other investigations of the material were carried
      out using X-ray diffraction (XRD), transmission electron microscopy (TEM),
      Brunauer Emmett Teller (BET) surface area analysis, thermogravimetric
      differential thermal analysis (TG-DTA), and dynamic light scattering (DLS)
      techniques. The synthesized material had an average crystallite size of ~5 nm and
      surface area of 252 +/- 10 m(2)/g. Sorption characteristics such as distribution
      ratios (K(d)), capacity, breakthrough profile, and elution behavior were
      investigated to ensure quantitative uptake of (188)W and selective elution of
      (188)Re. A 11.1 GBq (300 mCi) (188)W/(188)Re generator was developed using
      nanocrystalline gamma-Al(2)O(3), and its performance was evaluated for a period
      of 6 months. The overall yield of (188)Re was >80%, with >99.999% radionuclidic
      purity and >99% radiochemical purity. The eluted (188)Re possessed appreciably
      high radioactive concentration and was compatible for the preparation of (188)Re
      labeled radiopharmaceuticals.

PMID- 21726092
TI  - Method for optimizing coating properties based on an evolutionary algorithm
      approach.
AB  - In industry as well as many areas of scientific research, data collected often
      contain a number of responses of interest for a chosen set of exploratory
      variables. Optimization of such multivariable multiresponse systems is a
      challenge well suited to genetic algorithms as global optimization tools. One
      such example is the optimization of coating surfaces with the required absolute
      and relative sensitivity for detecting analytes using devices such as sensor
      arrays. High-throughput synthesis and screening methods can be used to accelerate
      materials discovery and optimization; however, an important practical
      consideration for successful optimization of materials for arrays and other
      applications is the ability to generate adequate information from a minimum
      number of experiments. Here we present a case study to evaluate the efficiency of
      a novel evolutionary model-based multiresponse approach (EMMA) that enables the
      optimization of a coating while minimizing the number of experiments. EMMA plans
      the experiments and simultaneously models the material properties. We illustrate
      this novel procedure for materials optimization by testing the algorithm on a sol
      gel synthetic route for production and optimization of a well studied amino
      methyl-silane coating. The response variables of the coating have been optimized
      based on application criteria for micro- and macro-array surfaces. Spotting
      performance has been monitored using a fluorescent dye molecule for demonstration
      purposes and measured using a laser scanner. Optimization is achieved by
      exploring less than 2% of the possible experiments, resulting in identification
      of the most influential compositional variables. Use of EMMA to optimize control
      factors of a product or process is illustrated, and the proposed approach is
      shown to be a promising tool for simultaneously optimizing and modeling
      multivariable multiresponse systems.

PMID- 21726093
TI  - N-1- and N-2-anthryl succinimide derivatives: C-N bond rotational behaviors and
      fluorescence energy transfer.
AB  - New rigid bicyclic N-anthrylsuccinimide 1a, 1b, 2a, and 2b were prepared. The
      C(aryl)-N(imide) bond rotational barriers, intra/intermolecular arene-arene
      interactions, and photophysical properties were investigated. The rotational
      behaviors are more significantly controlled by the position of C(aryl)-N(imide)
      connection than the sidewall framework. The fluorescence energy transfer
      (Phi(ET)) in 1a and 1b was estimated to be 61% and 53%, respectively. The
      difference is attributed to the position of C(aryl)-N(imide) connection, which
      directly influences the relative orientation of donor (naphthalene) and acceptor
      (anthracene).

PMID- 21726094
TI  - Evaluation of alpha-pyrones and pyrimidones as photoaffinity probes for affinity
      based protein profiling.
AB  - alpha-Pyrones and pyrimidones are common structural motifs in natural products
      and bioactive compounds. They also display photochemistry that generates high
      energy intermediates that may be capable of protein reactivity. A library of
      pyrones and pyrimidones was synthesized, and their potential to act as
      photoaffinity probes for nondirected affinity-based protein profiling in several
      crude cell lysates was evaluated. Further "proof-of-principle" experiments
      demonstrate that a pyrimidone tag on an appropriate scaffold is equally capable
      of proteome labeling as a benzophenone.

PMID- 21726095
TI  - Structure and bonding analysis of dimethylgallyl complexes of iron, ruthenium,
      and osmium [(eta5-C5H5)(CO)2M(GaMe2)] and [(eta5-C5H5)(Me3P)2M(GaMe2)].
AB  - Density functional theory calculations have been performed for the dimethylgallyl
      complexes of iron, ruthenium, and osmium [(eta(5)-C(5)H(5))(L)(2)M(GaMe(2)] (M =
      Fe, Ru, Os; L = CO, PMe(3)) at the DFT/BP86/TZ2P/ZORA level of theory. The
      calculated geometry of the iron complex [(eta(5)-C(5)H(5))(CO)(2)Fe(GaMe(2))] is
      in excellent agreement with structurally characterized complex [(eta(5)
      C(5)H(5))(CO)(2)Fe(Ga(t)Bu(2))]. The Pauling bond order of the optimized
      structures shows that the M-Ga bonds in these complexes are nearly M-Ga single
      bond. Upon going from M = Fe to M = Os, the calculated M-Ga bond distance
      increases, while on substitution of the CO ligand by PMe(3), the calculated M-Ga
      bond distances decrease. The pi-bonding component of the total orbital
      contribution is significantly smaller than that of sigma-bonding. Thus, in these
      complexes the GaX(2) ligand behaves predominantly as a sigma-donor. The
      contributions of the electrostatic interaction terms DeltaE(elstat) are
      significantly smaller in all gallyl complexes than the covalent bonding
      DeltaE(orb) term. The absolute values of the DeltaE(Pauli), DeltaE(int), and
      DeltaE(elstat) contributions to the M-Ga bonds increases in both sets of
      complexes via the order Fe < Ru < Os. The Ga-C(CO) and Ga-P bond distances are
      smaller than the sum of van der Waal radii and, thus, suggest the presence of
      weak intermolecular Ga-C(CO) and Ga-P interactions.

PMID- 21726096
TI  - Effect of SO2 on the transport properties of an imidazolium ionic liquid and its
      lithium solution.
AB  - Transport coefficients have been measured as a function of the concentration of
      sulfur dioxide, SO(2), dissolved in 1-butyl-2,3-dimethylimidazolium
      bis(trifluoromethylsulfonyl)imide, [BMMI][Tf(2)N], as well as in its lithium salt
      solution, Li[Tf(2)N]. The SO(2) reduces viscosity and density and increases
      conductivity and diffusion coefficients in both the neat [BMMI][Tf(2)N] and the
      [BMMI][Tf(2)N]-Li[Tf(2)N] solution. The conductivity enhancement is not assigned
      to a simple viscosity effect; the weakening of ionic interactions upon SO(2)
      addition also plays a role. Microscopic details of the SO(2) effect were
      unraveled using Raman spectroscopy and molecular dynamics (MD) simulations. The
      Raman spectra suggest that the Li(+)-[Tf(2)N] interaction is barely affected by
      SO(2), and the SO(2)-[Tf(2)N] interaction is weaker than previously observed in
      an investigation of an ionic liquid containing the bromide anion. Transport
      coefficients calculated by MD simulations show the same trend as the experimental
      data with respect to SO(2) content. The MD simulations provide structural
      information on SO(2) molecules around [Tf(2)N], in particular the interaction of
      the sulfur atom of SO(2) with oxygen and fluorine atoms of the anion. The SO(2)
      [BMMI] interaction is also important because the [BMMI] cations with above
      average mobility have a larger number of nearest-neighbor SO(2) molecules.

PMID- 21726097
TI  - Improvement of mitochondrial function in muscle of genetically obese rats after
      chronic supplementation with proanthocyanidins.
AB  - The aim of this study was to determine the effect of chronic dietary
      supplementation of a grape seed proanthocyanidin extract (GSPE) at a dose of 35
      mg/kg body weight on energy metabolism and mitochondrial function in the skeletal
      muscle of Zucker obese rats. Three groups of 10 animals each were used: lean
      Fa/fa lean group (LG) rats, a control fa/fa obese group (OG) of rats, and an
      obese supplemented fa/fa proanthocyanidins obese group (POG) of rats, which were
      supplemented with a dose of 35 mg GSPE/kg of body weight/day during the 68 days
      of experimentation. Skeletal muscle energy metabolism was evaluated by
      determining enzyme activities, key metabolic gene expression, and immunoblotting
      of oxidative phosphorylation complexes. Mitochondrial function was analyzed by
      high-resolution respirometry using both a glycosidic and a lipid substrate. In
      muscle, chronic GSPE administration decreased citrate synthase activity, the
      amount of oxidative phosphorylation complexes I and II, and Nrf1 gene expression,
      without any effects on the mitochondrial oxidative capacity. This situation was
      associated with lower reactive oxygen species (ROS) generation. Additionally,
      GSPE administration enhanced the ability to oxidize pyruvate, and it also
      increased the activity of enzymes involved in oxidative phosphorylation including
      cytochrome c oxidase. There is strong evidence to suggest that GSPE
      administration stimulates mitochondrial function in skeletal muscle specifically
      by increasing the capacity to oxidize pyruvate and contributes to reduced muscle
      ROS generation in obese Zucker rats.

PMID- 21726098
TI  - Comparative histological and immunohistochemical changes of dry type cutaneous
      leishmaniasis after administration of meglumine antimoniate, imiquimod or
      combination therapy.
AB  - BACKGROUND: This study compared histological and immunohistochemical changes of
      cutaneous leishmaniasis treated with meglumine antimoniate, imiquimod, and the
      combination of both therapies. METHODS: Single blind clinicopathological studies
      of fifteen patients with old world cutaneous leishmaniasis in Kerman, Iran were
      included. A total of four patients received a combination of imiquimod (5% cream)
      and intra-lesional meglumine antimoniate weekly for four weeks. Monotherapy with
      imiquimod was given to seven patients and four patients were treated with
      meglumine antimoniate intralesionally. Histological confirmation was performed
      before and during therapy. Semi-quantitative histological parameters such as
      numbers of mixed inflammatory cells (cells/mm(2)) and percentages of Langerhans
      cells (CD1a+), T-cells (CD3+), B-cells (CD20+), and macrophages (CD68+) were
      calculated immunohistochemically in the dermis and adjacent epidermis. RESULTS:
      Topical imiquimod significantly reduced mean histiocytic cellular aggregation
      size (P<0.05). Meglumine antimoniate reduced parasite load and infected activated
      histiocytes in the dermis (P<0.05). Meglumine antimoniate therapy decreased
      epidermal CD3+ lymphocytes but increased them in the dermis, within the
      granulomas (P<0.05). During topical application of imiquimod a depletion of CD1a+
      dendritic cells in the epidermis (P<0.05) and slight predominance of dendritic
      cells in the dermis were observed. Combined therapy and imiquimod monotherapy
      decreased CD68+ macrophages in the dermis (P<0.05). CONCLUSION: Meglumine
      antimoniate decreases parasite load with considerable effect on up-regulation of
      T-cells, which demonstrates that meglumine antimoniate works as parasitocidal and
      immunomodulator, which could be a first line of treatment. Imiquimod accentuates
      the host immune response and reduces granuloma size which could be effective
      immunomodulator for combination therapy. Monotherapy of imiquimod is less
      effective than the two other regimens in decreasing parasite load, inflammation
      and congestion at the inoculated site.

PMID- 21726099
TI  - In vitro differentiation of human bone marrow mesenchymal stem cells into
      hepatocyte-like cells.
AB  - BACKGROUND: Orthotropic liver transplantation (OLT) is the final procedure of
      both end stage and metabolic liver diseases. Hepatocyte transplantation is an
      alternative for OLT, but the sources of hepatocytes are limited. Bone marrow
      mesenchymal stem cells (BM-MSCs) can differentiate into hepatocyte-like cells and
      are a potential alternative source for hepatocytes. We aimed to investigate the
      differentiation potential of BM-MSCs into hepatocyte-like cells. METHODS: Human
      BM-MSCs from a healthy donor were cultured and differentiated into hepatocyte
      like cells. We investigated the expression of hepatocyte-specific markers in MSC
      derived hepatocyte-like cells (MSC-HLC) and evaluated their functionality using
      metabolic assays. RESULTS: MSC-HLCs expressed hepatocyte-specific markers at both
      mRNA and protein levels. In addition, the cells had the ability to uptake low
      density lipoprotein (LDL), clear ammonia, secrete albumin, and store glycogen.
      MSC-HLCs were transplanted into a familial hypercholesteromia patient.
      CONCLUSION: Human MSCs can be differentiated into partially functional hepatocyte
      like cells. Thus, they could be a potential source for cell therapy in liver
      disorders.

PMID- 21726100
TI  - Importance of including refractive error tests in school children's vision
      screening.
AB  - BACKGROUND: This study determined the importance of including tests for
      refractive errors in vision screening. METHODS: In this cross-sectional study, we
      performed a random cluster sampling of schoolchildren in the city of Dezful,
      Iran. After sampling and obtaining informed written consents from their parents,
      children underwent examinations at the school sites. Students underwent tests of
      visual acuity, cover tests and cycloplegic refractions. Elementary and middle
      school students who had a visual acuity of 20/20 or better in both eyes were
      included in the study. RESULTS: From 3673 elementary and middle school students,
      2957 (80.5%) had 20/20 vision or better. Of these, 16.1% [95% confidence interval
      (CI): 14.8 - 17.4] were ametropic, 0.4% had myopia and 10.1% had hyperopia. Mean
      sphere in those with hyperopia was +2.6+/-0.7 (range: +2.0 to +7.28) diopter (D).
      Astigmatism was detected in 6.6% and the mean cylinder was -0.9 (range: -0.75 to 
      3.25) D. The rate of anisometropia was 1.5% (95% CI: 0.8 - 2.0). CONCLUSION:
      Screening results of 20/20 vision for schoolchildren does not necessarily
      indicate normal eye status because hyperopia and astigmatism may still be sources
      of visual discomfort. To identify these cases and increase the sensitivity of
      screening tests, measurement of refractive errors by cycloplegic refraction tests
      might be included in vision screening.

PMID- 21726101
TI  - Plasma myeloperoxidase activity and apolipoprotein A-1 expression in chronic
      hepatitis B patients.
AB  - BACKGROUND: Hepatitis B virus initiates a complicated cascade process leading to
      chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. In inflammatory
      situations, myeloperoxidase is released in plasma and binds to apolipoprotein A-1
      in high-density lipoproteins. This study aims to evaluate the level of plasma
      myeloperoxidase as well as the pattern of plasma proteins in patients with
      chronic hepatitis B. METHODS: Included in this study were 30 male subjects: 19
      chronic hepatitis B patients, 6 HBV-related cirrhotic patients, and 5 healthy
      controls. Plasma myeloperoxidase was measured using enzyme-linked immunosorbent
      assay. Proteomic analysis of plasma proteins was performed by two-dimensional gel
      electrophoresis (2-DE) and mass spectrometry. One way ANOVA was used for data
      analysis. RESULTS: Mean plasma myeloperoxidase levels were higher in patients
      with liver cirrhosis (65.5+/-12.5; P=0.007) and chronic hepatitis B (53.7+/-10.6;
      P=0.18) when compared with healthy subjects (45+/-7.6). Moreover, a positive
      correlation was found between plasma myeloperoxidase levels and hepatic fibrosis
      stage (r=0.53, P=0.002; r=0.63, P=0.000). Proteomic analysis showed an altered
      plasma protein pattern in progressive hepatitis B and down-regulation of the
      major apolipoprotein A-1 along with the appearance of a variety of spots noted to
      be apolipoprotein A-1isoforms with different molecular masses. CONCLUSION: In
      this study, progressive liver injury due to HBV infection correlated with higher
      plasma myeloperoxidase and an altered plasma apolipoprotein A-1pattern.

PMID- 21726102
TI  - Manifestations of developmental dyslexia in monolingual Persian speaking
      students.
AB  - BACKGROUND: Manifestations of dyslexia depend on language systems and scripts.
      This study explored the prevalence and clinical features of developmental
      dyslexia among monolingual Persian students and provided insights on mechanisms
      involved in reading Persian. METHODS: To measure reading ability we developed a
      new instrument, Analysis of Persian Reading Ability, which had acceptable
      validity and reliability. A total of 1562 children aged 6 1/2 - 14 were randomly
      selected from a population of 109696 primary school students in the city of Qom,
      Iran. RESULTS: Using a variety of statistical and clinical criteria, 82 (5.2%) of
      the sample were classified as dyslexics. A detailed analysis of reading errors
      revealed eight types of errors related to three categories. The most frequent
      category in both dyslexic and the matched control group was phonological,
      followed by pragmatic and visual errors. CONCLUSION: The observed prevalence rate
      of dyslexia and reading error categories would suggest that Persian in vowel-free
      format is an opaque language and predominant use of a sub-lexical strategy is
      involved when reading Persian.

PMID- 21726103
TI  - Lead exposure changes gastric motility in rats: role of nitric oxide (NO).
AB  - BACKGROUND: Abdominal colic, constipation and delay in gastric emptying are
      symptoms of lead poisoning, but there is scant information about the effect of
      lead on gastric motility. In the present study, we investigated the effect of
      lead acetate on gastric motility in rats. METHODS: Animals were divided into nine
      groups (n=8); four groups were exposed to lead acetate solution (1%) for 1, 2, 3,
      and 4 weeks (Pb1, Pb2, Pb3, and Pb4 groups, respectively). Sodium acetate
      solution was given to another four groups for 1, 2, 3, and 4 weeks (Na1, Na2,
      Na3, and Na4 groups, respectively) and the control group had free access to tap
      water. Gastric motility was measured in the basal and acetylcholine (Ach)
      stimulated states using a physiograph instrument. Nitric oxide metabolite of
      gastric tissue was determined by Griess micro-assay. RESULTS: There were no
      significant differences between basal and Ach-stimulated gastric motility in Pb1,
      Pb2, Na1, and Na2 groups. However, it was significantly greater in Pb3 and Pb4
      groups when compared with Na3 and Na4 groups in both basal and Ach-stimulated
      states (P<0.05). In addition, nitric oxide metabolite of gastric tissue was more
      in all Pb groups in comparison with their Na counterparts (P<0.05). CONCLUSION:
      We found that lead exposure could affect gastric motility via the nitric oxide
      pathway.

PMID- 21726104
TI  - Effect of topiramate augmentation in chronic schizophrenia: a placebo-controlled
      trial.
AB  - BACKGROUND: The limitations of antipsychotics for treatment of schizophrenia have
      led to investigation of the usefulness of pharmacological augmentation
      strategies. Clinical studies have provided evidence for glutamate abnormalities
      in schizophrenia. Topiramate is an anticonvulsant drug with alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid receptor antagonist properties; therefore, the
      objective of the present study was to explore the therapeutic efficacy of
      topiramate as an adjunctive medication in schizophrenia. METHODS: A 17 week,
      double-blind, placebo-controlled clinical trial was performed on 80 patients (25 
      65 years) from 2005 - 2007. All were hospitalized in Mashhad psychiatric
      hospitals with chronic DSM-IV-TR-diagnosed schizophrenia. All participants
      received up to 300 mg/day of clozapine. In addition, participants randomly
      received either topiramate (200 - 300 mg/day) or placebo gradually added to their
      ongoing treatment. Efficacy of medication was measured by administering Positive
      and Negative Syndrome Scale at baseline and weeks 4, 8, 12, and 17. RESULTS:
      During the study, 5 patients from the placebo group and 12 participants from
      topiramate group were excluded. Clozapine and topiramate group showed significant
      decreases in all three subscales of PANSS values from baseline, with the maximum
      efficacy in week 12. However, after tapering topiramate, the general
      psychopathology sign was the only subscale that showed a significant difference.
      The clozapine and placebo group showed a significant decrease in all three
      subscales of PANSS values compared to baseline. The significant efficacy for all
      subscales was obtained at the end point. No significant differences in PANSS
      scores from baseline to end point were noted between case and control groups.
      CONCLUSION: Augmentation of clozapine and topiramate did not significantly
      decline patterns in any of the three subscales of PANSS compared to the clozapine
      and placebo group. Irct ID: IRCT138904014236N1

PMID- 21726105
TI  - Endoglin (CD105) positive microvessel density and its relationship with lymph
      node metastasis in squamous cell carcinoma of the tongue.
AB  - BACKGROUND: Neovascularization is an important factor for predicting tumor
      behavior. Evidence suggests that endoglin (CD105) is a powerful marker of
      neovascularization and determination of microvessel density in several
      malignancies, and can be used as an agent to predict lymph node metastasis.
      However, it is controversial, particularly in head and neck squamous cell
      carcinoma. We studied CD105-MVD in tongue squamous cell carcinoma and evaluated
      its correlation with lymph node metastasis in relation to sex, age, and
      histopathologic grade. METHODS: This study analyzed a total of 40 cases of tongue
      squamous cell carcinoma by dividing patients into two groups, a) with metastatic
      lymph nodes (N+) and b) without metastatic lymph nodes (N-). By CD105
      immunostaining, microvessel density was determined in three different areas
      (intratumoral, invasive front and adjacent normal tissue) of all cases.
      Statistically, we evaluated the relation between microvessel density and lymph
      node involvement, in addition to other clinicopathologic factors by using the
      Kolmogorov-Smirnov test, t-test, and other analyses. RESULTS: CD105-MVD in the
      invasive front (P<=0.001) and intratumoral (P<=0.006) areas of the N+ group was
      significantly higher than in the N-group. In addition, there was a correlation
      between CD105-MVD and differentiation in the invasive front area (P<= 0.013) No
      relation existed between CD105-MVD and other clinicopathologic features.
      CONCLUSION: CD105-MVD, as a prognostic factor, may be helpful for determining the
      possibility of lymph node metastasis of primary SCC of the tongue.

PMID- 21726106
TI  - Psychometric properties of the Persian version of the World Health Organization's
      quality of life questionnaire (WHOQOL-100).
AB  - BACKGROUND: In recent decades there has been increasing focus on developing and
      localizing quality of life (QOL) instruments in different societies. In this
      study, we aim to translate WHO's Quality of Life WHOQOL-100 questionnaire into
      the Persian language and assess the validity and reliability of the translated
      version. METHODS:   We used a forward-backward procedure to translate the
      questionnaire. A pilot sample of 60 university students was recruited to assess
      the repeatability and construct validity of the instrument. To assess the
      construct validity, 60 university students filled out both the WHOQOL-100 and
      WHOQOL-BREF questionnaires. Then, 500 healthy and 500 disabled individuals were
      randomly selected using a multi-stage sampling technique. The internal
      consistency of the Persian version of the WHOQOL-100 was evaluated using
      Cronbach's alpha in the sample. In addition, a multiple linear regression model
      was utilized for assessing the discriminant validity of this instrument,
      adjusting for different confounders. RESULTS: Test-retest analysis of data from
      the pilot sample showed that the Persian version of the WHOQOL-100 has acceptable
      repeatability (ICCs for all six domains were higher than 0.7). In addition,
      computation of the correlation between the domains of WHOQOL-100 and WHOQOL-BREF
      showed satisfactory construct validity. Analyzing the data from 500 healthy and
      500 disabled persons revealed that all domains of WHOQOL-100 met the minimum
      level of acceptable internal consistency. Multiple regression results showed
      acceptable discriminant validity for all domains of the Persian version, except
      for the spiritual domain. CONCLUSION: In general, the Persian version of the
      WHOQOL-100 had satisfactory reliability and validity for assessing QOL of Iranian
      people. However, we recommend further research for challenging the problem of the
      spiritual domain.

PMID- 21726107
TI  - Causes of hepatic granuloma: a 12-year single center experience from southern
      Iran.
AB  - BACKGROUND: Hepatic granuloma is reported in 2 - 15% of liver biopsy specimens.
      It is relatively easy for the pathologist to diagnose, but sometimes arriving at
      a specific etiology is quite difficult. Until now, there are few published
      studies about the etiology of hepatic granuloma in Iran. In this study, we
      attempt to determine the causes of hepatic granuloma from one of the largest
      referral centers in this country. METHODS: In a retrospective study over 12
      years, a hepatopathologist reviewed all liver biopsies with granuloma. The
      medical records, including clinical findings, autoantibodies, viral markers,
      imaging studies, drug histories, and all other specialized tests, such as
      molecular studies, were reviewed to reach a definite diagnosis. RESULTS: During
      12 years, there were 72 cases diagnosed with liver granuloma. The most common
      cause of hepatic granuloma was infectious, with Mycobacterium tuberculosis
      (52.8%). The second most common cause was visceral leishmaniasis in 8.3% of
      biopsies. Other less common causes were fungal infections, visceral larva
      migrans, primary biliary cirrhosis, and hepatitis C, each in 4.2% of cases.
      Autoimmune hepatitis was diagnosed in 2.8% of patients. Lymphoma, drug induced,
      disseminated BCGitis, CMV infection, foreign body reaction and sarcoidosis, were
      each found in 1.4% of the liver biopsies. After all investigations, there were
      12.5% idiopathic hepatic granulomas. CONCLUSION: According to this study, the
      most common cause of hepatic granuloma in Iran is tuberculosis. This finding is
      completely different from western countries and very similar to the results of
      countries such as Saudi Arabia.

PMID- 21726108
TI  - Dementia in Iran: how soon it becomes late!

PMID- 21726109
TI  - Remote cerebellar hemorrhage.
AB  - Postoperative cerebellar hemorrhage or remote cerebellar hemorrhage is a rare
      complication occurring after supratentorial and spinal surgery. Although the
      mechanism remains unclear, previous reports implicate over drainage of
      cerebrospinal fluid as the predominant cause. We report a patient who underwent
      craniotomy for removal of meningioma. The hemorrhage manifested a few days
      postoperatively as a headache and transient loss of consciousness. Our patient
      recovered without further intervention with no major neurologic deficit. Early
      detection and awareness of this complication may help to avoid unnecessary
      measures.  

PMID- 21726110
TI  - Primary glomus tumor of the liver.
AB  - Primary glomus tumors are extremely rare in the liver. To this date, only two
      cases of primary glomus tumors of the liver have been reported in the literature.
      This report is the third case of this specified tumor. The patient was a 50 year
      old Iranian woman who presented with a history of epigastric pain and nausea.
      Abdominal computed tomography (CT) scan showed a huge hepatic mass that replaced
      the entire left lobe. Surgical biopsy showed that the specimen consisted of a
      vascular network confined by the proliferation of epithelioid cells with round-to
      oval nuclei and eosinophilic cytoplasms. The cells expressed diffuse reactivity
      for vimentin, smooth muscle actin and CD34, whereas no reactivity was observed
      with carcinoembryonic antigen, synaptophysin, chromogranin, cytokeratin, and
      human melanoma black 45. We conclude that glomus tumors must be considered in the
      differential diagnosis of hepatic masses, with immunohistochemical staining for
      smooth muscle actin being a useful method to prove the diagnosis.

PMID- 21726111
TI  - Disseminated Mycobacterium tuberculosis in an infant with AIDS.
AB  - Disseminated Mycobacterium tuberculosis with involvement of liver, spleen, and
      bone marrow is a nonspecific and rare complication in human immunodeficiency
      virus (HIV) infected infants. Here, we report a six month old girl with fever,
      recurrent infections, bilateral axilary lymphadenitis, hepatomegaly, huge
      splenomegaly, and failure to thrive per the Center for Disease Control category
      of C for AIDS. The infant and her mother had positive enzyme immunoassay (EIA)
      and Western blot. HIV DNA PCR test of the infant was positive with subtype A (A1)
      in genotyping. A positive bone marrow aspirate staining for acid fast bacilli and
      PCR test on culture revealed Mycobacterium tuberculosis.

PMID- 21726112
TI  - Photoclinic. Actinomycetoma.

PMID- 21726113
TI  - Photoclinic. Teratoma.

PMID- 21726114
TI  - In memory of Iraj Afshar (1925 - 2011), a renowned scholar of Iranian studies.
AB  - On March 9th, 2011, the eminent scholar of Iranian studies, historian,
      bibliographer, Persian manuscript expert, journalist, biographer and writer, Iraj
      Afshar passed away at the age of 85 in Tehran. His demise was a great loss to
      Iranian culture. He edited or wrote around 300 books in various fields of Iranian
      studies, including the history of medicine in Iran and published more than 2000
      papers in local and international journals. The late Afshar was considered as a
      world-class Iranologist who promoted Persian culture for over five decades and
      had profitable mutual worldwide connection with famed scholars in the field of
      Iranian studies and pertinent international societies. Herein is a brief look at
      his life and career, with special focus on his works in the field of the history
      of medicine in Iran.

PMID- 21726115
TI  - Screening for gastrointestinal malignancy in patients with iron deficiency anemia
      by general practitioners: an observational study.
AB  - BACKGROUND: The prevalence of iron deficiency anemia (IDA) is 2-5% in men and
      postmenopausal women in the developed world. IDA is commonly caused by chronic
      gastrointestinal blood loss, and a thorough examination of the gastrointestinal
      tract must be standard practice. OBJECTIVE: To retrospectively study endoscopic
      evaluations of patients from general practitioners diagnosed with IDA in a
      peripheral hospital laboratory in order to determine the cause of IDA and the
      number of gastrointestinal malignancies. MATERIAL AND METHODS: We retrospectively
      evaluated all patients with IDA diagnosed in a peripheral hospital laboratory by
      the general practitioner in the region of our hospital from 1 January 2004 until
      31 December 2005. We included women older than 50 and men 18 years and older
      without a history of IDA in the previous 2 years. RESULTS: In 2 years, 287
      patients were newly diagnosed with IDA in our hospital laboratory. Only 90 (31%)
      patients were endoscopically evaluated within 4 months. Gastrointestinal
      endoscopy revealed at least one lesion potentially responsible for blood loss in
      41 of 90 (46%) patients. The most common lesions identified by gastroduodenal
      endoscopy were erosive esophagitis, gastritis and duodenitis (14%). Cancer was
      the most commonly detected lesion in the colon, accounting for 17 of 21 colonic
      lesions explaining IDA. In total, gastrointestinal malignancy was diagnosed in 2%
      of screened patients. Factors determining the decision for endoscopic screening
      were lower hemoglobin level, lower ferritin level and male gender. CONCLUSION: In
      our retrospective study of patients with IDA, only 31% received any form of
      endoscopic evaluation. In general practice, IDA is investigated suboptimally, and
      interventions other than the issuing of guidelines are needed to change practice.

PMID- 21726118
TI  - STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of
      different estrogen receptor-alpha immunoprofile.
AB  - Estrogen receptor (ER) is a major feature of endometrioid adenocarcinoma. It has
      a significant impact on constitution of estrogen-responsiveness of this
      endometrial malignancy, in which STAT3 (signal transducer and activator of
      transcription) becomes hyperactivated. The aim of our study was to detect
      immunohistochemically and compare expressions of STAT3 with apoptosis regulators
      (Bak and Bcl-xL) in regard to different pathological features and variably
      pronounced ER-alpha immunoprofile in 78 endometrioid adenocarcinomas. STAT3 was
      abundantly detected in nuclei of cancer cells in 54 cases, thus pointing at its
      activation as an universal nuclear transcriptional factor. Bcl-xL and Bak were
      expressed in cytoplasm of malignant cells in 62 and 20 cancers, respectively.
      STAT3 correlated both with Bcl-xL (p = 0.001, r = 0.365) and Bak (p  < 0.001, r =
      0.436) in all of endometrioid adenocarcinomas and variably in different subgroups
      of these tumours segregated in regard to grading, staging and patients' age.
      Remarkably, only ER-alpha positive cancers retained these correlations in
      opposition to ER-alpha negative tumours with negativity defined as an
      immunoreactivity below 10%. ER-alpha receptor probably enhances interactions
      between STAT3 and Bcl-xL to be present in statistically significant manner.
      Presence of ER-alpha receptor seems to be crucial for relationships among Bcl-xL
      and STAT3 to occur in endometrioid adenocarcinomas.

PMID- 21726119
TI  - Estrogen promotes B cell activation in vitro through down-regulating CD80
      molecule expression.
AB  - Estrogen is the main female hormone of women. It has diverse effects on cell
      growth, differentiation and homeostatic functions. Accumulated evidence has
      indicated that estrogen may regulate multiple immune functions and the immune
      status of women. However, there is little report on the effect of estrogen on
      mature B cell functions. In this study, we observed the effect of 17beta
      estradiol (E2) on the proliferation, apoptosis, antibody production and
      differentiation of splenic B cells of mice in vitro. Splenocytes of female BALB/c
      mice were isolated and cultured with E2. E2 treatments decreased the expression
      of CD80 molecule on splenic B cells but enhanced the total IgG antibody
      production of splenocyte, without promoting the differentiation of B cells to
      plasma cells. E2 protected splenic B cells from the serum-deficiency-induced
      apoptosis but had no influence on the proliferation of B cells. These results
      suggest that estrogen may promote the activity of B cells through down-regulating
      the expression of CD80 molecule on B cells.

PMID- 21726121
TI  - Patient satisfaction with a pressurized metered-dose inhaler with an integrated
      dose counter containing a fixed-dose mometasone furoate/formoterol combination.
AB  - INTRODUCTION: Inhaled delivery devices that are easy to use and facilitate dose
      tracking may lead to improved patient satisfaction and adherence. Patient
      satisfaction with a metered-dose inhaler (MDI) with an integrated dose counter
      containing a fixed-dose mometasone furoate/formoterol combination (MF/F MDI dose
      counter) was evaluated in subjects with persistent asthma or chronic obstructive
      pulmonary disease. METHODS: In this multicenter study (N = 272, age range: 12-92
      years), subject experience and satisfaction with MDI devices was evaluated using
      baseline and poststudy surveys. Subjects responded to the baseline survey based
      on their previous MDI experience, then received MF/F MDI 100/10 MUg with the
      integrated dose counter for 4 weeks before completing the poststudy survey. This
      evaluation was part of a broader study objective to assess performance of the
      MF/F MDI dose counter. RESULTS: At baseline, 52% of subjects reported being
      extremely satisfied with their previous MDI. After using the MF/F MDI dose
      counter, a relative increase of 43% in overall satisfaction was observed.
      Approximately 90% of subjects agreed the MF/F dose counter helped them track
      doses and was easy to use; >80% agreed the inhaler was of good quality and well
      designed. Subjects agreed the dose counter relieved anxiety about running out of
      medication (68%) or taking a subtherapeutic dose (65%). Nearly 80% of subjects
      had no reservations about the MF/F MDI dose counter, and most subjects stated
      they would request it from their physician (66%) and recommend it to a friend
      (75%). CONCLUSIONS: The MF/F MDI dose counter was found to be easy to use and
      have overall high patient satisfaction.

PMID- 21726122
TI  - Lack of association between CD58 genetic variations and aspirin-exacerbated
      respiratory disease in a Korean population.
AB  - BACKGROUND: Exacerbation of asthma symptoms due to aspirin ingestion may lead to
      life-threatening lung failure. The adhesion molecule CD58 gene may play a crucial
      role in aspirin-exacerbated respiratory disease (AERD) pathogenesis by mediating
      the biological functions of asthma-inducing mechanisms including T helper cells,
      proinflammatory cytokines, and natural killer T cells. OBJECTIVE: This study
      aimed to investigate the association of CD58 variations with aspirin-induced
      bronchospasm in Korean asthma patients. METHODS: Seven single-nucleotide
      polymorphisms were selected for genotyping based on previously reported
      polymorphisms in the International HapMap database. Genotyping was carried out
      using TaqMan assay and 2 major haplotypes were obtained in 163 AERD cases and 429
      aspirin-tolerant asthma controls. Frequency distributions of CD58 variations were
      analyzed using logistic and regression models. RESULTS: Results showed that none
      of the analyzed CD58 single-nucleotide polymorphisms and haplotypes was
      significantly associated with AERD development and fall rate of FEV(1) by aspirin
      provocation, an important diagnostic marker of aspirin hypersensitivity.
      CONCLUSIONS: This preliminary study suggests that CD58 does not affect AERD
      susceptibility in a Korean population, and may provide a new direction for future
      disease etiology.

PMID- 21726123
TI  - Formulation optimization of transdermal meloxicam potassium-loaded mesomorphic
      phases containing ethanol, oleic acid and mixture surfactant using the
      statistical experimental design methodology.
AB  - Response surface methodology (RSM) was used to develop and optimize the
      mesomorphic phase formulation for a meloxicam transdermal dosage form. A mixture
      design was applied to prepare formulations which consisted of three independent
      variables including oleic acid (X(1)), distilled water (X(2)) and ethanol (X(3)).
      The flux and lag time (LT) were selected as dependent variables. The result
      showed that using mesomorphic phases as vehicles can significantly increase flux
      and shorten LT of drug. The analysis of variance showed that the permeation
      parameters of meloxicam from formulations were significantly influenced by the
      independent variables and their interactions. The X(3) (ethanol) had the greatest
      potential influence on the flux and LT, followed by X(1) and X(2). A new
      formulation was prepared according to the independent levels provided by RSM. The
      observed responses were in close agreement with the predicted values,
      demonstrating that RSM could be successfully used to optimize mesomorphic phase
      formulations.

PMID- 21726124
TI  - Gastroretentive microparticles for drug delivery applications.
AB  - Many strategies have been proposed to explore the possibility of exploiting
      gastroretention for drug delivery. Such systems would be useful for local
      delivery, for drugs that are poorly soluble at higher pH or primarily absorbed
      from the proximal small intestine. Generally, the requirements of such strategies
      are that the vehicle maintains controlled drug release and exhibits prolonged
      residence time in the stomach. Despite widespread reporting of technologies, many
      have an inherent drawback of variability in transit times. Microparticulate
      systems, capable of distributing widely through the gastrointestinal tract, can
      potentially minimise this variation. While being retained in the stomach, the
      drug content is released slowly at a desired rate, resulting in reduced
      fluctuations in drug levels. This review summarises the promising role of
      microencapsulation in this field, exploring both floating and mucoadhesive
      microparticles and their application in the treatment of Helicobacter pylori,
      highlighting the clinical potential of eradication of this widespread infection.

PMID- 21726125
TI  - Arterial elasticity and oxidized LDL among men with metabolic syndrome and
      different 10-year cardiovascular risk estimated by FINRISK and SCORE models.
AB  - BACKGROUND: SCORE and FINRISK models are designed to estimate patient's risk for
      cardiovascular diseases (CVD). Increased circulating oxidized LDL (oxLDL) and
      impaired arterial elasticity, on their part, are considered as markers of
      subclinical atherosclerosis. Subjects with metabolic syndrome (MetS) are thought
      to be at high risk for CVD because of metabolic abnormalities. AIM: To study
      among men with MetS whether subjects with three, four, or five MetS variables or
      different estimated 10-year CVD risk differ in oxLDL and arterial elasticity.
      METHODS: OxLDL was assessed by a capture ELISA and arterial elasticity by a
      radial artery tonometer among 120 men with MetS. Ten-year CVD risk was calculated
      for those without CVD or statin medication by FINRISK and SCORE at the actual age
      and at the extrapolated age of 60. Results. High-risk subjects by FINRISK and
      SCORE had impaired arterial elasticity. In addition, high-risk subjects by
      FINRISK at the extrapolated age had elevated oxLDL levels. The number of MetS
      variables did not associate with arterial elasticity or oxLDL. CONCLUSION: Among
      men with MetS, estimation of 10-year CVD risk, especially when extrapolated to
      age 60, seems to differentiate subjects with respect to markers of subclinical
      atherosclerosis. Trial registration. ClinicalTrials.gov NCT01119404.

PMID- 21726126
TI  - CNS regulation of plasma cholesterol.
AB  - The incidence of disorders related to the control of energy homeostasis, such as
      hypertension, diabetes, obesity, and dyslipidemia, has dramatically increased
      worldwide in the last decades. The central nervous system (CNS) plays a critical
      role regulating the energy balance, therefore there has been increasing interest
      in understanding the mechanisms whereby the brain controls peripheral metabolism,
      in order to develop new potential therapies to treat those disorders. While the
      involvement of the CNS in development of hypertension, obesity, and diabetes has
      been thoroughly investigated, less is known about the specific role of the brain
      in the control of circulating lipids. Here we summarize the evidence linking CNS
      disorders with dyslipidemia, as well as the central mechanisms that directly
      influence plasma cholesterol.

PMID- 21726127
TI  - Anti-lipid peroxidation and induction of apoptosis in the erythroleukaemic cell
      line K562 by extracts from (Tunisian) Rhamnus alaternus L. (Rhamnaceae).
AB  - Total oligomer flavonoids (TOF) enriched and ethyl acetate (EA) extracts from
      Rhamnus alaternus induce apoptotic death in human chronic myelogenous leukaemia
      K562 cell line, as demonstrated by gel electrophoresis, which demonstrates the
      characteristic ladder patterns of DNA fragmentation and the proteolytic cleavage
      of poly(ADP ribose) polymerase (PARP). The effect of R. alaternus extract in
      reducing oxidative stress was evaluated by anti-lipid peroxidation which was
      monitored by measuring malondialdehyde level in K562 cultured cells. The TOF and
      EA extracts were found to be effective to protect against lipid peroxidation.
      Their IC50 values were 196 and 273 ug mL-1, respectively. These findings suggest
      that R. alaternus extracts exhibit potential antioxidant and proapoptotic
      properties.

PMID- 21726128
TI  - In vitro antibacterial activity of some Iranian medicinal plant extracts against
      Helicobacter pylori.
AB  - Helicobacter pylori infection causes lifelong chronic gastritis, which can lead
      to peptic ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric
      cancer. The growing problem of antibiotic resistance by the organism demands the
      search for novel candidates from plant-based sources. In the present study, we
      evaluated the in vitro anti-H. pylori activity of some selected medicinal plants
      on clinical isolates of H. pylori. Gastric biopsy samples were obtained from
      patients presenting with gastroduodenal complications. Helicobacter pylori was
      isolated from the specimens following standard microbiology procedures. The disc
      diffusion method was used to determine the susceptibility of three H. pylori
      isolates to methanol extracts of 23 Iranian plants. All tests were performed in
      triplicate. Among them, the extracts of Punica granatum and Juglans regia had
      remarkable anti-H. pylori activity with mean of inhibition zone diameter of 39
      and 16 mm at 100 ug disc-1, respectively. In view of the results obtained with P.
      granatum (pomegranate), the peel extracts of nine cultivars of pomegranate
      (Shirin-e-Pust Sefid, Agha Mohammad Ali-e-Shirin, Sefid-e-Shomal, Sefid-e-Torsh,
      Shirin-e-Malase, Tabestani-e-Torsh, Shirin-e-Saveh Malase, Alak-e-Shirin, Pust
      Siyah) were further assayed against the clinical isolates of H. pylori. The
      results revealed that all Iranian pomegranate cultivars, except for Alak-e
      Shirin, showed significant in vitro anti-H. pylori activity against the clinical
      isolates of H. pylori (mean of inhibition zone diameter ranging from 16 to 40 mm
      at 50 ug disc-1).

PMID- 21726129
TI  - Inhibition of HIV-1 reverse transcriptase associated activities by the
      hydroalcoholic extract of Casimiroa edulis seeds.
AB  - The hydroalcoholic extract obtained from the seeds of Casimiroa edulis cultivated
      in Sardinia (Italy) have been assayed on the two enzymatic-associated activities
      of the HIV-1 reverse transcriptase (RT), the RNA-dependent DNA polymerase (RDDP)
      and the ribonuclease H. In biochemical assays, the extract inhibited both
      activities in a dose-dependent manner, showing a 10-fold more potent inhibition
      of the HIV-1 RT RDDP activity. Furthermore, the extract was cytotoxic on K562
      cell replication.

PMID- 21726130
TI  - Antimicrobial activities of essential oil and methanol extract of Coriaria
      nepalensis.
AB  - Plant extracts and products have been used for centuries in traditional medicine;
      for most of them, in addition to the scant scientific credibility, the chemical
      composition and spectrum of activity are yet to be explored. To put forward this
      effort and to identify novel antimicrobial agents, the inhibitory activities of
      methanolic extract and essential oil from Coriaria nepalensis against various
      microorganisms including pathogenic yeast, and Gram-positive and negative
      bacteria were evaluated. Chemical compositions of C. nepalensis methanolic
      extract and essential oil were analysed by gas chromatography-mass spectrometry.
      In vitro susceptibility tests against all the tested isolates were performed in
      terms of minimum inhibitory concentration (MIC), and well diffusion assay using
      standard protocols. All microorganisms tested were profoundly found susceptible
      to both the C. nepalensis extract and oil with MIC values of 1.3-2.1 mg mL-1
      (Gram-positive bacteria), 1.4-2.2 mg mL-1 (Gram-negative bacteria) and 0.9-1.6 mg
      mL-1 (yeasts). The extent of inhibition was shown more by methanolic extract than
      by essential oil. This study is the first to report the antimicrobial activity of
      extracts obtained from the C. nepalensis. It can be concluded that the observed
      antimicrobial characteristics of C. nepalensis indicate that it might be a
      promising antimicrobial agent.

PMID- 21726131
TI  - Anti-inflammatory and analgesic effects of human placenta extract.
AB  - In this study, we investigated the effects of human placenta extract (HPE,
      Laennec inj.) on pro-inflammatory cytokines and mediators secreted from
      lipopolysaccharide-stimulated RAW264.7 macrophages. We found that HPE
      significantly inhibited the production of nitric oxide, tumour necrosis factor
      alpha and cyclooxygenase-2. We studied the anti-inflammatory and analgesic
      potential of HPE in murine models of inflammation/inflammatory pain. Rats were
      assigned to six groups and were administered either saline or HPE (0.33, 1, 3 and
      6 mL kg-1) intraperitoneally. Diclofenac was used as a positive control. HPE
      attenuated the swelling of the rat's hind paw. The vascular permeability induced
      by acetic acid was significantly reduced by HPE. HPE reduced the formation of
      granuloma in carrageenan air pouch and hind paw oedema in complete Freund's
      adjuvant-induced chronic arthritis in rats. HPE attenuated writhing episodes. An
      increase in hot-plate latency was observed in mice receiving HPE. HPE also
      increased the pain threshold in the Randall-Selitto test. In the tail-flick
      assay, HPE prolonged the reaction time of rats to radiant heat stimulation. These
      results suggest that HPE has potent anti-inflammatory and anti-nociceptive
      activities.

PMID- 21726132
TI  - Antioxidant activity of phenolic and flavonoid compounds in some medicinal plants
      of India.
AB  - In this study, total phenolics, flavonoids and vitamin C content vis-a-vis
      antioxidant activities were assayed in leaves and stem bark of Azadirachta
      indica, Butea monosperma, Cassia fistula, Mangifera indica, Syzygium cumini and
      Tamarindus indica using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide
      radical scavenging method. The DPPH radical scavenging activity positively
      correlated with the total phenolic content in both stem bark and leaf. Superoxide
      radical scavenging activity increased with increasing flavonoid contents.
      However, the vitamin C content could not be correlated with DPPH and superoxide
      radical scavenging capacity.

PMID- 21726133
TI  - Hypolipidemic potential of flowers of Nerium oleander in high fat diet-fed
      Sprague Dawley rats.
AB  - Nerium oleander Linn. (NO), an evergreen shrub, is used in folklore medicine as a
      cardiotonic and exhibits a wide spectrum of bioactivities. Herein, the
      hypolipidemic potential of the ethanolic extract of flowers of Nerium oleander
      (ENO) in a minimal dose was assessed. A high fat diet (HFD) resulted in a
      significant increase in cardiac lipids and lipoproteins and an increase in body
      weight gain. Simultaneous treatment with ENO significantly lowered the increase
      in body weight gain, lipid and lipoprotein levels, with a concomitant increase in
      HDL in the plasma and heart when compared to HFD-fed rats. Likewise, the
      activities of lipolytic enzymes were also upheld by the ENO treatment in the
      heart compared to HFD-fed rats. The above findings highlight the possible
      mechanism of N. oleander as a hypolipidemic agent in its use in folklore medicine
      as a cardiotonic.

PMID- 21726134
TI  - Functionalized silica-based nanoparticles for photodynamic therapy.
AB  - AIM: The strategy developed aims to favor the vascular effect of photodynamic
      therapy by targeting tumor-associated vascularization using peptide
      functionalized nanoparticles. We previously described the conjugation of a
      photosensitizer to a peptide targeting neuropilin-1 overexpressed in tumor
      angiogenic vessels. MATERIALS & METHODS: In this study, we have designed and
      photophysically characterized a multifunctional nanoparticle consisting of a
      surface-localized tumor vasculature targeting peptides and encapsulated
      photodynamic therapy and imaging agents. RESULTS & CONCLUSION: The elaboration of
      these multifunctional silica-based nanoparticles is reported. Nanoparticles
      functionalized with approximately 4.2 peptides bound to recombinant neuropilin-1
      protein. Nanoparticles conferred photosensitivity to cells overexpressing
      neuropilin-1, providing evidence that the chlorin grafted within the nanoparticle
      matrix can be photoactivated to yield photocytotoxic effects in vitro.

PMID- 21726135
TI  - Iron core/shell nanoparticles as magnetic drug carriers: possible interactions
      with the vascular compartment.
AB  - AIMS: Nanomagnets with metal cores have recently been shown to be promising
      candidates for magnetic drug delivery due to higher magnetic moments compared
      with commonly used metal oxides. Successful application strongly relies on a safe
      implementation that goes along with detailed knowledge of interactions and
      effects that nanomagnets might impart once entering the body. MATERIALS &
      METHODS: In this work, we put a particular focus on the interactions of ultra
      strong metal nanomagnets (>= three-times higher in magnetization compared with
      oxide nanoparticles) within the vascular compartment. Individual aspects of
      possible effects are addressed, including interactions with the coagulation
      cascade, the complement system, phagocytes and toxic or inflammatory reactions
      both by blood and endothelial cells in response to nanomagnet exposure. RESULTS:
      We show that carbon-coated metal nanomagnets are well-tolerated by cells of the
      vascular compartment and have only minor effects on blood coagulation.
      CONCLUSION: These findings provide the fundament to initiate successful first in
      vivo evaluations opening metal nanomagnets with improved magnetic properties to
      fascinating applications in nanomedicine.

PMID- 21726136
TI  - Development and evaluation of nanosized niosomal dispersion for oral delivery of
      Ganciclovir.
AB  - Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to
      enhance the oral absorption and prolong the existence of the drug in the systemic
      circulation. So the purpose of the present study was to improve the oral
      bioavailability of Ganciclovir by preparing nanosized niosomal dispersion.
      Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of
      1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal
      dispersions were characterized for entrapment efficiency, size, shape, in vitro
      drug release, release kinetic study, and in vivo performance. Optimized
      formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly
      high encapsulation of Ganciclovir (89+/-2.13%) with vesicle size of 144+/-3.47 nm
      (polydispersity index [PDI]=0.08). The in vitro release study signifies sustained
      release profile of niosomal dispersions. Release profile of prepared formulations
      have shown that more than 85.2+/-0.015% drug was released in 24 h with zero-order
      release kinetics. The results obtained also revealed that the types of surfactant
      and Cholesterol content ratio altered the entrapment efficiency, size, and drug
      release rate from niosomes. In vivo study on rats reveals five-time increment in
      bioavailability of Ganciclovir after oral administration of optimized formulation
      (NG8) as compared with tablet. The effective drug concentration (>0.69 ug/mL in
      plasma) was also maintained for at least 8 h on administration of the niosomal
      formulation. In conclusion, niosomes can be proposed as a potential oral delivery
      system for the effective delivery of Ganciclovir.

PMID- 21726137
TI  - Animal models of idiosyncratic drug-induced liver injury--current status.
AB  - The infrequent occurrence of idiosyncratic reactions and their dependence on
      individual sensitivity factors allow them to go undetected in current preclinical
      safety evaluation using conventional animal tests. Better predictive models for
      idiosyncratic, drug-induced liver injury (IDILI) would enable the preclinical
      elimination of drug candidates with idiosyncrasy liability and could provide
      evidence for a mode of action for these responses, suggest early biomarkers of
      IDILI, and lead to the development of mechanism-based, in vitro screens.
      Desirable characteristics of an animal model include the production of liver
      injury in a large fraction of animals of relatively inexpensive species/strains
      and the ability to distinguish drugs that cause IDILI in humans from ones that do
      not. The mechanistic basis for idiosyncratic reactions remains poorly understood.
      However, attempts at animal model development have been made based on several
      hypothesized modes of action of IDILI. These hypotheses have centered on drug
      disposition polymorphisms, adaptive immunity, mitochondrial dysfunction, failure
      to adapt to modest injury, inflammatory stress, and multiple determinants, and
      the success in achieving animal models of liver injury for each of these is
      discussed. Despite numerous challenges associated with animal models of IDILI,
      some models have emerged and are proving useful in exploring potential
      mechanisms. Current animal models are not perfect, but they hold promise for
      increasing the prediction and understanding of human idiosyncratic drug
      reactions.

PMID- 21726139
TI  - Sowing simulation tests of a pneumatic drill equipped with systems aimed at
      reducing the emission of abrasion dust from maize dressed seed.
AB  - The utilization of dressed seed for spring sowing is a widespread practice to
      control some pests with reduced doses of chemical products. However some
      insecticides employed in maize seed dressing, namely belonging to the
      neonicotinoid family and fipronil, have been claimed to play a role in the
      decline of honeybees (Apis mellifera L.). Pneumatic drills used in maize sowing
      are charged with contributing to the dispersion of the abrasion dust produced by
      dressed seeds, favoring the contamination of the honeybee habitat. Different
      devices similar to air deflectors have been introduced on pneumatic drills in
      order to reduce dust drift. During previous field tests carried out by the
      authors during recent years reduction of dust concentration both in the air and
      at soil surface has been shown as a consequence of their application. As field
      tests are affected by the variability of environmental parameters (namely wind
      speed and direction) the results are not always reliable, comparable and of a
      general validity. This paper refers to a sowing simulation test system in which
      pneumatic drills can be tested at a fixed point under controlled conditions of
      the main environmental parameters. In the test area, protected by external
      influences, artificial wind conditions are created by means of a fan. The drill,
      suitably placed in the test area, operates the seed distribution "sur place" by
      means of an electric engine connected to the drill's driving wheel. A 22.5 m long
      sampling area, leeward with respect to the drill position, has been identified.
      Along the sampling area a series of Petri dishes has been placed, with the aim of
      capturing the depositing dust and providing the concentration of the active
      ingredients (a.i.) at ground level. At the same time, three air samplers with
      PTFE diskette filters have been used for the detection of the a.i. The test
      system has been used for the test of a pneumatic drill, equipped with and without
      air deflectors, using maize seed dressed with four a. i. (imidacloprid,
      clothianidin, thiametoxam, fipronil). The results showed regularly decreasing of
      the concentrations as distance increased, both in the air and at ground level.
      Moreover, the difference determined by the adoption of the drift reducing device
      (air deflectors) resulted clear and it can be quantified at around 50 % of the
      a.i. amounts observed without deflectors. Finally, the paper proposes a data
      processing method that, from the values observed at fixed point, provides the
      theoretical a.i. concentration behavior that would occur in field, under the same
      conditions of wind speed and direction and working speed. The obtained results
      are coherent with previous field test.

PMID- 21726140
TI  - Novel imazethapyr detoxification applying advanced oxidation processes.
AB  - Different degradation methods have been applied to assess the suitability of
      advanced oxidation process (AOPs) to promote mineralization of imazethapyr [(RS)
      5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid], a widely
      used imidazolinone class herbicide, the persistence of which has been
      demonstrated in surface and ground waters destined to human uses. Independent of
      the oxidation process assessed, the decomposition of imazethapyr always followed
      a pseudo-first order kinetic. The direct UV-irradiation (UV) of the herbicide as
      well as its oxidation with ozone (O3), and hydrogen peroxide tied to UV
      irradiation (H2O2/UV) were sufficiently slow to permit the identification of
      intermediate products, the formation pathway of which has been proposed.
      Ozonation joined to UV-irradiation (O3/UV), ozonation joined to titanium dioxide
      photo-catalysis (TiO2/UV+O3), sole photo-catalysis (TiO2/UV), and photo-catalysis
      reinforced with hydrogen peroxide-oxidation (TiO2/UV+H2O2) were characterized by
      a faster degradation and rapid formation of a lot of small molecules, which were
      quickly degraded to complete mineralization. The most effective oxidation methods
      were those using titanium dioxide photo-catalysis enhanced either by ozonation or
      hydrogen peroxide. Most of all, these last processes were useful to avoid the
      development of dangerous by-products.

PMID- 21726141
TI  - The adsorption and degradation of chlorpyriphos-methyl, pendimethalin and
      metalaxyl in solid urban waste compost.
AB  - To evaluate the feasibility of using compost to prepare substrates for the
      disposal of pesticide residues, adsorption and degradation studies were carried
      out on three widely used agricultural pesticides: chlorpyriphos-methyl,
      pendimethalin and metalaxyl. Obtained from solid urban waste, this compost has
      been shown to be able to adsorb high levels of chlorpyriphos-methyl and
      pendimethalin (85%, 100%) whereas metalaxyl was only adsorbed at a level of 37%.
      However, adding smectite to the compost increased the adsorption of metalaxyl by
      117%. Chlorpyriphos-methyl and pendimethalin degraded quickly with half-lives of
      1.7 and 14.5 days, respectively, whereas metalaxyl proved more persistent (a half
      life of 84 days). Adding ammonium nitrate to the compost accelerated metalaxyl
      degradation to a half-life of 15 days.

PMID- 21726142
TI  - Losses and dissipation of penconazole in vineyard soil as affected by mid-row
      management system.
AB  - A field experiment was performed with the aim to assess the amount of penconazole
      losses during field application and the spatial variability of penconazole
      concentration in a vineyard soil, under two different management techniques
      (tilled and grass covered). The field dissipation of penconazole under the two
      techniques was also followed for 114 days, highlighting the effects of spatial
      variability of the initial concentration and of the grass covering in terms of
      the different soil metabolic activity. Data found show that a high percentage of
      penconazole, from 42.5 % to 67.43 %, can reach the soil during the treatments,
      despite the fact that penconazole is applied to the foliage. The high values of
      the coefficient of variation for data within rows show considerable variability
      in all applications, ranging from 30 to 65 in the first application, from 35 to
      79 in the second and from 36 to 75 in the third. Since the applications of
      penconazole occurred under almost same climatic conditions in terms of wind speed
      and direction, the high variability of concentration of penconazole found within
      mid-rows was attributed to the uneven slope of the vineyard causing an irregular
      speed of the sprayer equipment. However, least significant differences of the
      mean values did not end in a significant difference of penconazole concentration
      among mid-rows for all applications, indicating that the variability between rows
      does not contribute to the overall variability. The calculated half-life values
      for penconazole in tilled soil were 62.4 days for tilled and 33.0 for grassed
      soil, highlighting the tendency of penconazole to faster dissipate in grassed
      than in tilled soil. Grassed soil was characterised by a higher metabolic
      activity in terms of microbial biomass carbon content, basal respiration and
      total hydrolytic activity, than tilled soil. A significant correlation between
      penconazole dissipation and total hydrolytic activity, was found. The faster
      dissipation of penconazole in grassed soil was attributed to the higher amount of
      the total hydrolytic activity which, in grassed soil, was 1.5 fold-higher than in
      tilled soil.

PMID- 21726143
TI  - Preliminary study on persistence in soil and residues in maize of imidacloprid.
AB  - The aim of this work was to study the distribution of imidacloprid in soil and
      its translocation to roots and aerial parts of maize plant. The main objective
      was to assess imidacloprid residues in field environment, in order to provide
      data on honeybees exposure level to such an active substance. Imidacloprid has
      been detected and quantified by Triple Quadrupole HPLC-MS-MS. Pesticide
      persistence in the soil and its residues in pollen and in maize plants have been
      evaluated during the growing of maize plants developed from seeds dressed with
      Gaucho 350 FS (imidacloprid: 1.0 mg/seed). The sowing has been performed by means
      of a pneumatic precision drill. Samples have been collected at 30, 45, 60, 80,
      130 days after the sowing, as pollen samples have been collected at the
      tasseling. Imidacloprid presence in aerial part of maize plant declined to 2-3
      MUg/kg 80 days after the sowing, while concentration in kernel at harvest was <1
      MUg/kg. Maize pollen represents an important part of protein supply of beehives,
      and it is of critical importance to bee foraging. The values detected
      (imidacloprid residues <1 MUg/kg) showed that maize pollen source should not be
      relevant for acute toxicity impact on honey bees.

PMID- 21726144
TI  - Insecticidal activity of different extracts from Scrophularia canina L. against
      Culex pipiens molestus Forskal (Diptera, Culicidae).
AB  - The insecticidal activity of different extracts (aqueous, methyl alcohol, hexane
      and petroleum ether) of the aerial part of Scrophularia canina against the second
      and fourth-instar larvae and adult females of Culex pipiens molestus was
      investigated. The larvicidal activity of all the extracts was tested in the dose
      range from 7.8 to 1000 ppm. The highest toxicity was exhibited by the petroleum
      ether extract against second-instar larvae (48 h LC50 = 23.5 ppm) and by the
      hexane extract against fourth-instar larvae (48 h LC50 = 23.6 ppm). Methyl
      alcohol and aqueous extracts did not show any larvicidal activity. Sub-lethal
      doses of petroleum ether and hexane extracts induced increasing mortalities
      during 13 days after treatment but did not affect the duration of larval and
      pupal stages. In persistence tests, the hexane extract retained a satisfactory
      larvicidal activity after a 10-day period of test solutions incubation. Topical
      treatment of adult females with doses from 0.25 to 8 MUg per mg of female body
      weight of different extracts showed a similar toxicity for the hexane (24 h LD50
      = 1.7 MUg mg-1) and petroleum ether (24 h LD50 = 1.8 MUg mg-1) extracts which
      were significantly more toxic than methyl alcohol extract (4.2 MUg mg-1). Aqueous
      extract did not induce adult mortality. The marked mosquitocidal activity of
      petroleum ether and hexane extracts of the aerial part of S. canina against
      different life stages of C. pipiens molestus is promising to develop effective
      alternatives to synthetic insecticides.

PMID- 21726145
TI  - Preliminary evaluation of insecticide resistance in a strain of Musca domestica
      (Diptera: Muscidae) from an intensive chicken farm of Northern Italy.
AB  - The house fly, Musca domestica L., a relevant sanitary pest, is mainly controlled
      by insecticides. However, an inappropriate use of chemicals may induce
      resistance, treatment efficacy decline and environmental damages. We evaluated
      toxicity of some organophosphates, pyrethroids, spinosad and neonicotinoids by
      topical applications on adults of a M. domestica strain (OcRo) collected from an
      intensive chicken farm in Northern Italy, in comparison to a susceptible strain
      (s-DBF). The OcRo strain exhibited higher levels of resistance (RR50) to four
      pesticides in comparison to s-DBF. Spinosad and imidacloprid had very low RR50,
      thus were still efficient in OcRo control. We also tested resistance to
      pesticides in OcRo after topical applications of synergistic compounds.
      Hydrolases were involved in phosphorganic detoxification and cytochrome P450
      monoxygenases in that of pyrethroids. These results indicate that OcRo strain is
      now multiresistant to organophosphates and pyrethroids, and this should be
      considered for an environmentally safe pest management.

PMID- 21726146
TI  - Insecticidal activity and fungitoxicity of plant extracts and components of
      horseradish (Armoracia rusticana) and garlic (Allium sativum).
AB  - To avoid environmental pollution and health problems caused by the use of
      traditional synthetic pesticides, there is a trend to search for naturally
      occurring toxicants from plants. Among the compounds discussed for anti-fungal
      and insecticidal activity, the natural extracts from garlic and horseradish have
      attracted considerable attention. The objective of this study is to determine the
      insecticidal and anti-fungal activity of Armoracia rusticana and Allium sativum
      L. extracts against larvae of Aedes albopictus (Skuse) and some pathogenic fungi.
      For the insecticidal test, horseradish and garlic extracts were prepared from
      fresh plants (cultivated in Emilia Romagna region) in a solution of ethanol 80 %
      and the two different solutions were used at different concentrations (for the
      determination of the lethal dose) against the fourth instar mosquito's larvae.
      The fungicidal test was carried out by the agar plates technique using garlic and
      horseradish extracts in a 10 % ethanol solution against the following organisms:
      Sclerotium rolfsii Sacc., Trichoderma longibrachiatum, Botrytis cinerea Pers.,
      Fusarium oxysporum Schlecht. and Fusarium culmorum (Wm. G. Sm.) Sacc. The first
      results demonstrated that the horseradish ethanol extracts present only a
      fungistatic activity against Sclerotium rolfsii Sacc., Fusarium oxysporum
      Schlecht. and F. culmorum (Wm.G. Sm) Sacc. while garlic extracts at the same
      concentration provided a good fungicidal activity above all against Botrytis
      cinerea Pers. and S. rolfsii. A. rusticana and A. sativum preparations showed
      also an interesting and significant insecticidal activity against larvae of A.
      albopictus, even if horseradish presented a higher efficacy (LC50 value of 2.34
      g/L), approximately two times higher than garlic one (LC50 value of 4.48 g/L).

PMID- 21726147
TI  - Influence of fenamidone, indoxacarb, pyraclostrobin, and deltamethrin on the
      population of natural yeast microflora during winemaking of two sardinian grape
      cultivars.
AB  - The influence of fenamidone ((S)-1-anilino-4-methyl-2-methylthio-4
      phenylimidazolin-5-one), pyraclostrobin (methyl 2-[1-(4-chlorophenyl)pyrazol-3
      yloxymethyl]-N-methoxycarbanilate), indoxacarb (methyl 7-Chloro-2,5-dihydro-2
      [[(methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno[1,2
      e][1,3,4] oxadiazine-4a(3H)-carboxylate), and deltamethrin ([cyano-[3
      (phenoxy)phenyl]methyl] 3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane-1
      carboxylate) on spontaneous fermentation carried out by natural yeast grapes
      microflora, was studied during the wine-making process. Aliquots of pesticide
      standard solutions were added to the grapes before crushing, to reach a
      concentration equal or half the maximum residue limit (MRL). Vinifications were
      performed, with maceration (R), or without maceration (W). During the wine-making
      process, samples were taken at the beginning (one hour after grapes crushing), at
      the middle and at the end of the spontaneous fermentation process. At half the
      MRL concentration, deltamethrin affected Pichia sp. population with a decrease of
      almost 50 %, while fenamidone decreased Candida sp., Candida stellata at 83, and
      36%, respectively. Metschnikowia pulcherrima population decreased in all samples
      when compared to the control. Experiments at MRL levels showed a strong reduction
      for all non-Saccharomyces yeast species, when grapes had been treated with
      pyraclostrobin, fenamidone, and deltamethrine, except for Candida sp. which was
      found to have been affected only by fenamidone residues. Growth zone inhibition
      test showed only an in vitro activity of pyraclostrobin over Kloeckera spp., C.
      stellata, and M. pulcherrima. Microvinification experiments produced wines with
      no differences concerning S. cerevisiae population as well as production of
      ethanol and residual sugars. Experiments showed that at the end of the
      fermentation process pesticides were adsorbed by the lees and grape skins, and no
      pesticides residue was detectable in wine.

PMID- 21726148
TI  - Evaluation of groundwater contamination in a coastal area of south-eastern
      Sicily.
AB  - This investigation was under taken to evaluate the groundwater resources
      contamination due to intensive agricultural practices (particularly greenhouses).
      The study-area is located in the coastal area of the Ragusa province (South-East
      Sicily), where numerous existing greenhouses may cause the contamination of
      groundwater systems (unconfined and confined aquifers) beneath the cropped land.
      The pollution risk is mainly related with the seepage process of macro-elements
      nitrogen (N), phosphorus (P), potassium (K), held in the irrigation water and the
      massive use of fertilizers and pesticides, that may pass through the unsaturated
      zone of the soil profile. Moreover, the area is characterized by the presence of
      several wells (about 15 wells/km2) for agricultural use that cause the aquifer
      overexploitation and the consequent risk of seawater intrusion. The agriculture
      practices adopted in the study area (irrigation volumes, fertilizer
      concentrations, use of pesticides...) were monitored since February 2009;
      moreover, the pollution risk of the aquifers was evaluated through the analysis
      of groundwater water samples collected (monthly) in the monitoring wells; in
      particular, nitrogen compounds, soluble phosphorous (PO42-), potassium, as well
      as the main pesticides commonly used in the study area, were measured.The results
      show that electrical conductivity and chloride concentration values can cause
      reduction of production and leaf damage problems, respectively, for most of the
      monitored farm systems. The high nitrogen compounds concentrations observed in
      the monitored wells can cause health and environmental problems. Moreover high
      pesticide contamination of groundwater was found in two of the five monitored
      wells.

PMID- 21726149
TI  - Development of monoclonal antibody-based immunoassays for the analysis of
      bisphenol A in canned vegetables.
AB  - The aim of this work was the development of monoclonal antibodies (MAbs) and
      highly sensitive immunoassays (ELISAs) to bisphenol A (BPA), a well-known
      endocrine disruptor able to migrate from the internal coating of cans to food
      contained inside, particularly vegetables. To produce MAbs to BPA, four synthetic
      compounds were conjugated to proteins and used as immunizing haptens in mice. By
      applying hybridoma technology, several MAbs were produced and selected. These
      antibodies were characterized in the conjugate-coated and in the antibody-coated
      formats, using both homologous and heterologous conjugates. Three indirect ELISA
      based on the MAbs showing the highest affinity to BPA were selected. The limit of
      detection of the most sensitive ELISA was 0.22 nM (0.05 ng/mL), with an I50 value
      of around 1 nM (0.23 ng/mL). An homologous ELISA based on the MAb BPAB-11 was
      applied to the simple, direct determination of BPA in the liquid portion of
      canned artichoke, peas, and sweet corn. Only sample dilution in an appropriate
      saline buffer was required to minimize matrix effects and to enter the ELISA
      working range. Recovery and precision of the method were evaluated by spiking the
      liquid portion of these cans with BPA at 20, 50, and 100 ng/mL. Coefficients of
      variation were below 20% in most cases. With regard to recovery, the analytical
      data obtained were also acceptable. This immunoassay has therefore proved its
      potential as a new tool for the rapid, sensitive and accurate determination of
      BPA in canned food.

PMID- 21726150
TI  - Residues of pirimiphos-methyl in cereals and processed fractions following post
      harvest spray application.
AB  - The aim of this work was to comparatively assess the persistence of pirimiphos
      methyl residues in cereals and in their milling fractions after spray application
      in post harvest. An analytical method, based on a slightly modified QuEChERS
      extraction followed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
      determination was validated: mean recovery was in the range 73% to 92% depending
      on the spiking level, and precision as RSD ranged from 11% to 16%. The analysis
      of treated samples revealed that pirimiphos-methyl residues were highly
      persistent and that no differences could be observed between wheat, durum wheat
      and oat. As far as the impact of the milling process on residues is concerned,
      pirimiphos methyl contamination was significantly reduced during both cleaning
      and processing, and most of the contamination was related to outer kernel
      fractions.

PMID- 21726151
TI  - Determination of sixteen pesticides in peppers using high-performance liquid
      chromatography/mass spectrometry.
AB  - A method for the detection and quantification of 16 pesticides: flufenoxuron,
      fenoxycarb, dimethomorph, acetamiprid, imidacloprid, lufenuron, thiacloprid,
      thiabendazole, thiophanate-methyl, spinosad, fenbutatin oxide, methoxyfenozide,
      oxamyl, clothianidin, thiamethoxam and carbendazim has been developed based on
      high-performance liquid chromatography-mass spectrometry. Pesticide residues were
      extracted from the samples according to the QuEChERS method which stands for
      quick, essay, cheap, effective, rugged and safe. Homogenised analytical portions
      (10 g +/- 0.1) of samples of peppers were spiked at two levels (10 and 100 MUg kg
      1) with a small volume of an appropriate standard mixture solution containing
      each pesticide. Analyses were performed using electrospray ionization (ESI) and a
      MSD trap system. Chromatography separation was achieved using a ZORBAX SB-C18 3.5
      MUm particle size analytical column, 2.1 * 50 mm from Agilent, with gradient
      elution at a flow-rate of 0.4 mL/min with mobile phases: waters-0.1 % HCOOH-5 mM
      HCOONH4 and MeOH-5 mM HCOONH4. The method has been validated based on the SANCO
      European Guidelines. Under the optimized conditions the recoveries (n = 7) were
      in the range 70-110 % with satisfactory precision (CV <= 20 %). A linear dynamic
      range was obtained over a range of concentrations from 10 to 100 MUg kg-1 for
      each of the analytes, with correlation coefficients >0.997.

PMID- 21726152
TI  - Validation of an analytical method for the quantification of pyrethrins on lemons
      and apricots using high-performance liquid chromatography/mass spectrometry.
AB  - An analytical procedure has been developed for the determination of natural
      pyrethrins (pyrethrin I, pyrethrin II, jasmolin I, jasmolin II, cinerin I and
      cinerin II) in lemon and apricot. The QuEChERS method, which stands for quick,
      easy, cheap, effective, rugged and safe was used for extraction. Analysis of the
      extract was performed by liquid-chromatography-electrospray ionisation-tandem
      mass spectrometry. The ions prominent in the ESI spectra were [M+H]+ for the six
      compounds. A Zorbax SB-C18 column was used with a programmed gradient mobile
      phase consisting of (A) water containing 0.1% formic acid and 5 mM ammonium
      formate and (B) ACN. The method was linear within the investigated concentration
      range, displaying a calibration curve correlation factor of 0.99. The
      coefficients of variation obtained (RSD) were below 20% and the recoveries were
      in the 70-110% range.

PMID- 21726153
TI  - Determination of acidic herbicides in cereals by QuEChERS extraction and
      LC/MS/MS.
AB  - A simple and rapid method has been studied for the determination of acidic
      herbicides (2,4-D, Dichlorprop, Dichlorprop-p, Fluazifop, Fluroxypyr, MCPA,
      Mecoprop and Mecoprop-p) on cereals (rye). The method involves an alkaline
      hydrolysis with sodium hydroxide in order to release covalently bound compounds,
      prior to QuEChERS extraction, followed by neutralization and analysis via liquid
      chromatography-double mass spectrometry LC/MS/MS. The performance of the method
      either with or without alkaline hydrolysis was studied in terms of recovery rates
      and limit of quantification (LOQ). In either case, recoveries were determined at
      four spiking levels (0.02 mg/kg, 0.05 mg/kg, 0.1 mg/kg and 0.5 mg/kg) with 5
      replicates for each level. Mean recoveries ranged from 90 to 120 %, whereas
      relative standard deviations (RSD %) proved to be less than 20 %. Quantitative
      analysis was carried out by the internal standard (Nicarbazin) and the LC/MS/MS
      analysis was performed in electrospray ionisation (ESI) negative mode using a
      Zorbax XCB Eclipse column. The developed method was applied to the analysis of
      several cereals commercially available like as rye flour, oat meal, oat flakes
      and dehusked oat. Residue levels were found below the limit of quantification
      (LOQ) of the method. The method has been tested in EU Proficiency Tests for
      cereals with good results.

PMID- 21726154
TI  - Chlorpyrifos residues levels in fruits and vegetables after field treatment.
AB  - Chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate) was
      applied with three different formulations on oranges, peaches, tomatoes, wine and
      table grapes, and its behaviour was evaluated after field treatment. The
      formulations applied were emulsifiable concentrates (EC), microencapsulates (ME),
      and wettable granules (WG). The residues were similar in all crops studied in the
      EC and WG experiments, except peaches with WG treatment, the residue amount was
      lower than EC values. Tomatoes which were grown in greenhouse showed similar
      residues in all treatments just after treatment. Wine and table grapes showed
      different decline curves in the EC experiments ascribable to the different
      growing technology. Instrumental limit of determination (LOD) and limit of
      quantification (LOQ) for all matrices were 0.01, and 0.03 mg kg-1, respectively.
      Repeated treatments showed that Chlorpyrifos can accumulate leading to residue
      levels at the preharvest interval (PHI) over the maximum residue level (MRL),
      especially on oranges and peaches. Among the formulates used ME showed the higher
      risk of residues over the MRL at harvest.

PMID- 21726155
TI  - Determination of acibenzolar-S-methyl and its acidic metabolite in soils by HPLC
      diode array detection.
AB  - A simple and accurate method for the analysis of acibenzolar-S-methyl
      (benzo[1,2,3]thiadiazole-7-carbothioic acid-S-methyl ester; CGA 245 704; ASM) and
      its major conversion product, benzo[1,2,3]thiadiazole-7-carboxylic acid (CGA 210
      007; BTC), in soils is presented. ASM extraction from soil samples was performed
      using acetonitrile and BTC was extracted with a mixture of potassium phosphate
      buffer (0.5 M, pH 3) and acetonitrile (70:30 %, v/v). Both extracts were directly
      analyzed in a high-performance liquid chromatography-diode array detection (HPLC
      DAD) system. Pesticide separation was achieved on a C18 (4.6 mm * 150 mm, 5 MUm)
      analytical column with a isocratic elution of acetonitrile:water 40:60 % (v/v)
      with 0.6 mL L-1 acetic acid at a flow rate of 1 mL min-1. Linear regression
      coefficients (r (2)) of the external calibration curves were always above 0.9997.
      The limits of detection (LOD) and quantification (LOQ) of the method were 0.005
      and 0.02 mg kg-1 for ASM, and 0.01 and 0.05 mg kg-1 for BTC, respectively.
      Recoveries were investigated at six fortification levels and were in the range of
      90-120 % for ASM and 74-96 % for BTC with relative standard deviations (RSDs)
      below 11 % in all cases. The method was also validated by analyzing freshly
      spiked soil samples with 2.7% organic matter content at 0.5 mg kg-1 level, with
      slightly lower recovery values only for ASM. Moreover, recoveries for
      intermediate aged residues of the analytes were similar to fresh residues. This
      method was also applied to determine ASM half-life (t(1/2) = 8.7 h) and the rate
      of the acidic metabolite formation.

PMID- 21726156
TI  - The metabolically healthy but obese postmenopausal woman presents a favourable
      heart rate variability profile.
AB  - OBJECTIVE: The purpose of this study was to investigate the heart rate
      variability (HRV) profile in obese women displaying the metabolically healthy but
      obese (MHO) phenotype. DESIGN: We studied 47 obese, sedentary postmenopausal
      women. Subjects were classified as MHO or at risk based on insulin resistance as
      assessed with the homeostatic model assessment (HOMA) index. Subjects were
      divided into tertiles according to HOMA values. Subjects in the lower tertile
      were categorised as MHO while subjects in the upper 2 tertiles represented at
      risk subjects. Outcome measures were heart rate variability factors (RR
      intervals, SDNN, LF, HF, pNN50, RMSSD), body temperature, body composition (DEXA)
      and a lipid profile as well as glucose and insulin. RESULTS: MHO individuals had
      significantly lower resting heart rate, body temperature, lean body mass as well
      as fasting insulin and HOMA levels compared to at risk subjects (p < 0.05). In
      addition, RR intervals, SDNN and LF were significantly higher in MHO individuals
      (p < 0.05). Moreover, stepwise regression analysis showed that SDNN was an
      independent predictor of the variation in HOMA in our cohort. CONCLUSION: Results
      of the present study indicate that postmenopausal women displaying the MHO
      phenotype present a favourable HRV profile. Therefore, higher HRV could be
      associated, at least in part, in the protective profile of MHO individuals.

PMID- 21726157
TI  - Laser-generated air contaminants from medical laser applications: a state-of-the
      science review of exposure characterization, health effects, and control.
AB  - The clinical use of lasers in surgery began in 1973 with applications of the
      carbon dioxide laser in otolaryngology, and since then the use of lasers has
      become commonplace in many medical and surgical specialties. Nonetheless, when
      biological tissue is subjected to laser radiation, the target cells can be
      vaporized, resulting in the aerosolization of their contents and the subsequent
      exposure of health care workers to laser-generated air contaminants (LGACs). The
      purpose of our analysis was to summarize and present all of the published
      literature pertaining to the laser-induced plume chemical and physical
      composition, health effects, and methods of control. The objective was to
      identify knowledge gaps within exposure science to set a research agenda for the
      protection of health care personnel exposed to LGACs. A literature search was
      performed using the PubMed database using a variety of search strategies and
      keyword combinations. To locate additional studies, we systematically searched
      the reference lists of all studies identified by our search, as well as key
      review papers. To date, researchers have identified roughly 150 chemical
      constituents of plume, as well as fine and ultrafine particulate matter, which
      has been shown to include viable cellular material, viruses, and bacteria.
      However, very few studies have attempted to characterize the effects of laser
      system type, power, and tissue treated, as it relates to LGAC exposure.
      Furthermore, current control strategies do not appear to be adequate in
      preventing occupational exposure to LGACs.

PMID- 21726158
TI  - The mediational role of perceived stress in the relation between optimism and
      burnout in competitive athletes.
AB  - Burnout has been highlighted as an important issue, not only in occupational
      settings but also among athletes. Optimists appear to be more resistant to
      burnout, which might be partly explained by lower levels of stress. The purpose
      of this study was to investigate the relationship between optimism and burnout
      symptoms in 217 athletes (139 males and 78 females, aged 16 to 19 years), while
      also examining stress as a mediator in this relationship. The results showed that
      optimism had a significant negative relationship with both stress and burnout.
      Mediation analyses indicated that perceived stress fully mediated the links
      between optimism and two symptoms of burnout, emotional/physical exhaustion and
      sport devaluation, and partly mediated the link between optimism and a third
      symptom, reduced sense of accomplishment. The findings indicate that individual
      factors, such as optimism, may play an important role in the development of
      burnout by virtue of their association with stress. Future research should,
      therefore, investigate the longitudinal effects of optimism on stress and
      burnout.

PMID- 21726159
TI  - Parents and family members in the era of ART: evidence from Cambodia and
      Thailand.
AB  - Ensuring treatment adherence is critical for the success of antiretroviral
      therapy (ART) programs in developing countries. Enlisting NGOs or persons living
      with HIV/AIDS (PLHA) group members as treatment supporters is one common
      strategy. Less attention is given to family members and especially older-age
      parents. Yet ART patients often live with other family members who are highly
      motivated to ensure treatment success. This study examines the role of family
      members and especially parents in assisting adherence in Cambodia and Thailand
      among adult ART patients. Most have a living parent and many live with or near a
      parent. Family members including parents commonly remind patients to take
      medications, particularly if coresident in the same household. Parents also
      remind patients to get resupplies and accompany them to appointments. Some
      contrasts between Cambodia and Thailand emerged. Fewer Cambodian than Thai
      patients had a living parent. However, among those who did, equal shares lived
      with parents. Cambodian parents more commonly reminded patients to take
      medications and get resupplies and accompanied them when doing so. In both
      countries correct knowledge of ART among parents was associated with the amount
      of advice from program personnel. The results underscore both the need to more
      explicitly incorporate close family members, including parents, into efforts to
      promote adherence and need for PLHA peers and home based care teams to provide
      them with adequate information, training and resources to increase their
      effectiveness.

PMID- 21726160
TI  - Evaluation of the pharmacokinetics, preclinical and clinical efficacy of
      pralatrexate for the treatment of T-cell lymphoma.
AB  - INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of T
      cell neoplasms. Most patients with PTCL have a poor outcome with conventional
      therapies and are not cured without stem-cell transplantation. Pralatrexate, a
      novel antifolate chemotherapeutic agent, was rationally designed to impede folate
      metabolism by inhibiting dihydrofolate reductase (DHFR) and to be more
      efficiently internalized into tumor cells. Pralatrexate is the first drug that is
      FDA approved for patients with relapsed and refractory PTCL. AREAS COVERED:
      Pralatrexate has been used as a single agent and in combination with other agents
      in clinical trials for non-Hodgkin's lymphoma and Hodgkin's disease as well as in
      solid tumors. This review will cover the development of pralatrexate, the
      pharmacokinetics of pralatrexate, preclinical findings with pralatrexate and
      clinical studies of pralatrexate in hematologic malignancies. EXPERT OPINION:
      Pralatrexate has significant activity in vitro, and in early Phase I/II trials,
      responses were noted in patients with aggressive T-cell lymphomas. The
      Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma
      trial demonstrated the activity of pralatrexate across a spectrum of heavily
      pretreated patients with different aggressive T-cell lymphoma subtypes, and
      studies in cutaneous T-cell lymphoma have shown efficacy at different doses and
      schedules. The most frequent adverse events in these trials were mucositis,
      reversible thrombocytopenia and fatigue.

PMID- 21726161
TI  - Almotriptan for menstrually related migraine.
AB  - INTRODUCTION: Approximately 50% of migrainous women associate their headache
      temporally to menses. Menstrually related migraine (MRM) is a disabling form of
      migraine characterized by attacks that are generally longer, more severe and less
      drug-responsive than nonmenstrual ones. Since MRM may be difficult to treat, it
      is important to find an appropriate treatment option for women suffering from
      this condition. AREAS COVERED: This paper provides an overview of the clinical
      features of MRM, with special attention on the use of almotriptan for its
      treatment. Four studies on almotriptan in the treatment of MRM are present in the
      medical literature. Two report post hoc analyses of data derived from larger
      studies on the use of almotriptan for migraine treatment. One reports the results
      from a study specifically dedicated to MRM and one illustrates a subanalysis on
      the accompanying symptomatology. EXPERT OPINION: Evidence demonstrates that
      almotriptan is a molecule with a high efficacy in the treatment of MRM and with
      an excellent tolerability profile when compared with other triptans. Moreover, it
      shows a proven ability to control migraine-associated symptoms. All these
      qualities play a decidedly positive role in making almotriptan a product of
      choice for the treatment of MRM.

PMID- 21726162
TI  - Athlete's biological passport: to test or not to test?

PMID- 21726163
TI  - The Athlete Biological Passport from the perspective of an anti-doping
      organization.
AB  - The introduction of the Athlete Biological Passport is a landmark in the fight
      against doping. Contrary to traditional toxicological anti-doping analysis, its
      aim is to detect the biological consequences of doping through the measurement of
      different specific biomarkers which generate individual profiles for each
      athlete. This new approach allows anti-doping organizations to convict those
      athletes showing abnormal profiles for the use (not the presence!) of even
      undetectable forbidden substances or methods. Additionally, these data can be
      used for other purposes: to conduct targeted conventional anti-doping tests on
      those athletes showing unusual results and to evaluate the prevalence of doping
      within a population of athletes. By now only the hematological biomarkers of
      blood doping have been validated, but in the future additional modules will be
      introduced to detect other forms of doping.

PMID- 21726164
TI  - Bayesian analysis of an international ELISA comparability study.
AB  - BACKGROUND: Immunoassays are biochemical tests applied to measure even very small
      amounts of substance using the highly specific binding between an antibody and
      its antigen. They have a wide range of applications. The measurement however,
      might be associated with substantial uncertainty; this can have significant
      consequences for any diagnosis, or clinical decision. An international
      comparability study was thus performed to assess the sources of uncertainty
      involved in the estimation of a protein cytokine concentration using a
      fluorescent ELISA. METHODS: In contrast to the original publication for this
      international comparability study, we reanalyse the data using Bayesian
      inference. This provides a statistically coherent approach to estimate ELISA
      concentrations and their associated uncertainties. RESULTS: The Bayesian
      uncertainties of individual ELISAs and laboratory estimates are considerably
      larger than previously reported uncertainties. The average concentrations
      estimated here differ from the ones estimated by each study participant. In
      general, this leads to different conclusions about the study. In particular, the
      inter- and intra-laboratory consistency is increased, and repeatability problems
      occur for fewer laboratories. CONCLUSIONS: Decisions which are based on plausible
      ranges of measurements (such as credible intervals), are generally superior to
      those solely based on point estimates (such as the mean). Reliable uncertainties
      are thus vital, and not only in metrology. In this paper, a general method is
      developed to derive concentration estimates and valid uncertainties for ELISAs.
      Guidance on applying this Bayesian method is provided and the importance of
      reliable uncertainties associated with ELISAs is underlined. The applicability
      and virtues of the presented method are demonstrated in the context of an
      international comparability study.

PMID- 21726165
TI  - New biomarkers for acute renal injury.
AB  - Incidence of acute kidney injury (AKI) is increasing rapidly to epidemic
      proportions. Development of AKI, especially in intensive care settings, is
      associated with increased morbidity, mortality and hospitalization costs.
      Currently available diagnostic tools are mostly insensitive for early diagnosis,
      however prompt diagnosis and risk stratification are necessary for guiding
      therapy and preventing progression of disease. Finding an early, reliable,
      suitable, easily reproducible, economical and accurate biomarker for AKI is a top
      research priority. In recent years, many urinary and serum proteins have been
      investigated as possible early markers of AKI and some of them have shown great
      promise. This topic reviews some of the emerging biomarkers of AKI.

PMID- 21726166
TI  - Relationship between bilirubin and C-reactive protein.
AB  - BACKGROUND: Epidemiologic studies have shown that serum total bilirubin is
      inversely related to an increased risk of coronary artery disease. However, the
      number of studies which have focused on the relationship between bilirubin and C
      reactive protein (CRP), which is a marker reflecting chronic vascular
      inflammation, are limited. METHOD: This cross-sectional study consisted of 2307
      Korean adults who visited the Center for Health Promotion for a routine health
      check-up from January 2009 to December 2009. RESULT: CRP level showed a declining
      tendency as total bilirubin increased according to total bilirubin quartiles.
      Negative relations of CRP with both total and direct bilirubin were found after
      adjustment of age, body mass index, hypertension, diabetes, hypercholesterolemia,
      cardiovascular disease, taking aspirin, smoking, alcohol drinking and regular
      exercise and total bilirubin or direct bilirubin. CONCLUSIONS: This study found
      that elevation of the two types of bilirubin (total and direct) have a
      relationship with a low serum CRP level among apparently healthy Korean adults.
      It is hypothesized that a low serum CRP level may be due to the antioxidant and
      anti-inflammatory effects of bilirubin metabolism.

PMID- 21726167
TI  - Functional assay or antigen test for protein C and protein S in ischemic stroke:
      which shows the greatest change?

PMID- 21726168
TI  - Impact of intrapartal ultrasound to assess fetal head position and station on the
      type of obstetrical interventions at full cervical dilatation.
AB  - OBJECTIVES: Recent ultrasound studies have shown that it is feasible to
      objectively and reproducibly assess fetal head position and station within the
      pelvis. We sought to evaluate the impact of this new approach on decision making
      by physicians in a cohort of women with a prolonged second stage of labor.
      METHODS: This was a retrospective cohort study that included all women with
      fetuses in cephalic presentation, who were diagnosed with a prolonged second
      stage of labor, and who delivered in a 1-year period. We compared a group of
      women (n = 121) with a prolonged second stage of labor who underwent intrapartal
      ultrasound prior to obstetrical intervention (Group A, n = 43) with a group of
      women for whom the delivery modus was decided upon after clinical digital
      examination alone (Group B, n = 78). RESULTS: There were no significant
      differences in maternal and neonatal morbidity between both groups. The rate of
      second-stage cesarean section was significantly higher (p < 0.50) in Group B
      without ultrasound compared to Group A with ultrasound prior to operative
      delivery (20/78 vs. 7/43). Seven patients in Group A delivered spontaneously, but
      none of the patients in Group B had spontaneous deliveries. CONCLUSIONS:
      Intrapartal ultrasound in patients with a prolonged second stage of labor may
      change obstetrical practice by reducing the number of second stage cesarean
      section without increasing maternal and neonatal morbidity.

PMID- 21726169
TI  - K252a suppresses neuronal cells apoptosis through inhibiting the translocation of
      Bax to mitochondria induced by the MLK3/JNK signaling after transient global
      brain ischemia in rat hippocampal CA1 subregion.
AB  - It is demonstrated that the c-Jun N-terminal kinase (JNK) signaling pathway plays
      a critical role in ischemic brain injury. Our previous studies have suggested
      that K252a can obviously inhibit JNK activation induced by ischemia/reperfusion
      in the vulnerable hippocampal CA1 subregion. Here, we further discussed the
      potential mechanism of ischemic brain injury induced by the activation of JNK
      after 15?min of transient global cerebral ischemia. As a result, through
      inhibiting phosphorylation of Bcl-2 (a cytosolic target of JNK) and 14-3-3
      protein (a cytoplasmic anchor of Bax) induced by the activation of JNK, K252a
      decreased the release of Bax from Bcl-2/Bax and 14-3-3/Bax dimers, further
      attenuating the translocation of Bax from cytosol to mitochondria and the release
      of cytochrome c induced by ischemia/reperfusion, which related to mitochondria
      mediated apoptosis. Importantly, pre-infusion of K2525a 20?min before ischemia
      showed neuroprotective effect against neuronal cells apoptosis. These findings
      imply that K252a induced neuroprotection against ischemia/reperfusion in rat
      hippocampal CA1 subregion via inhibiting the mitochondrial apoptosis pathway
      induced by JNK activation.

PMID- 21726170
TI  - In vitro metabolism of nobiletin, a polymethoxy-flavonoid, by human liver
      microsomes and cytochrome P450.
AB  - Cytochrome P450 enzymes (CYPs) in the liver metabolize drugs prior to excretion,
      with different enzymes acting at different molecular motifs. At present, the
      human CYPs responsible for the metabolism of the flavonoid, nobiletin (NBL), are
      unidentified. We investigated which enzymes were involved using human liver
      microsomes and 12 cDNA-expressed human CYPs. Human liver microsomes metabolized
      NBL to three mono-demethylated metabolites (4'-OH-, 7-OH- and 6-OH-NBL) with a
      relative ratio of 1:4.1:0.5, respectively, by aerobic incubation with
      nicotinamide adenine dinucleotide phosphate (NADPH). Of 12 human CYPs, CYP1A1,
      CYP1A2 and CYP1B1 showed high activity for the formation of 4'-OH-NBL. CYP3A4
      catalyzed the formation of 7-OH-NBL with the highest activity and of 6-OH-NBL
      with lower activity. CYP3A5 also catalyzed the formation of both metabolites but
      considerably more slowly than CYP3A4. In contrast, seven CYPs (CYP2A6, CYP2B6,
      CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1) were inactive for NBL. Both
      ketoconazole and troleandomycin (CYP3A inhibitors) almost completely inhibited
      the formation of 7-OH- and 6-OH-NBL. Similarly, alpha-naphthoflavone (CYP1A1
      inhibitor) and furafylline (CYP1A2 inhibitor) significantly decreased the
      formation of 4'-OH-NBL. These results suggest that CYP1A2 and CYP3A4 are the key
      enzymes in human liver mediating the oxidative demethylation of NBL in the B-ring
      and A-ring, respectively.

PMID- 21726171
TI  - Racemates revisited: heterochiral assemblies and the example of DL-thalidomide.
AB  - The existence of racemic compounds, comprised of pairs of opposite enantiomers as
      discrete molecular entities, has been accepted for over a century. However, their
      ability to remain as associated dimers when in solution is uncertain, if not
      generally doubted. In this article, data has been assembled to provide evidence
      for the presence of intact dimeric heterochiral assemblies in solution and
      presents DL-thalidomide as a probable example of this phenomenon.

PMID- 21726172
TI  - Drug interaction potential of toremifene and N-desmethyltoremifene with multiple
      cytochrome P450 isoforms.
AB  - Toremifene is an effective agent for the treatment of breast cancer in
      postmenopausal women and is being evaluated for its ability to prevent bone
      fractures in men with prostate cancer taking androgen deprivation therapy. Due to
      the potential for drug-drug interactions, the ability of toremifene and its
      primary circulating metabolite N-desmethyltoremifene (NDMT) to inhibit nine human
      cytochrome P450 (CYP) enzymes was determined using human liver microsomes.
      Induction of CYP1A2 and 3A4 by toremifene was also investigated in human
      hepatocytes. Toremifene did not significantly inhibit CYP1A2 or 2D6. However,
      toremifene is a competitive inhibitor of CYP3A4, non-competitive inhibitor of
      CYP2A6, 2C8, 2C9, 2C19 and 2E1 and mixed-type inhibitor of CYP2B6. CYP inhibition
      by NDMT was similar in magnitude to toremifene. Toremifene did not induce CYP1A2
      but increased CYP3A4 monooxygenase activity and gene expression in drug-exposed
      human primary hepatocytes. Although clinical doses of toremifene produce steady
      state exposures to toremifene and NDMT that may be sufficient to cause
      pharmacokinetic drug-drug interactions with other drugs metabolised by CYP2B6,
      CYP2C8, CYP3A4, CYP2C9 and CYP2C19, these data indicate that toremifene is
      unlikely to play a role in clinical drug-drug interactions with substrate drugs
      of CYP1A2 and CYP2D6.

PMID- 21726173
TI  - Correlation of midtrimester amniotic fluid cytokine concentrations with adverse
      pregnancy outcome in terms of spontaneous abortion, preterm birth, and
      preeclampsia.
AB  - OBJECTIVE: To assess midtrimester amniotic fluid concentrations of three major
      proinflammatory cytokines (IL-6, IL-8, and TNF-alpha) in asymptomatic pregnancies
      with adverse outcomes. METHODS: A prospective follow up study at the Charite
      University Hospital, Berlin, Germany of women with uncomplicated singleton
      pregnancies at second trimester and amniocentesis. Concentrations of IL-6, IL-8,
      and TNF-alpha were measured by enzyme-linked immunosorbent assay following
      amniotic fluid assessment by midtrimester amniocentesis performed from gestation
      days 15 weeks 0 days up to 20 weeks 6 days. Values from normal pregnancies were
      compared to those from pregnancies having adverse outcomes of spontaneous
      abortion, preterm delivery, preeclampsia, or eclampsia. Main outcome measure IL
      6, IL-8 and TNF-alpha in relation to adverse pregnancy outcome. RESULTS: A total
      of 298 consecutive patients were evaluated. Median patient age was 35 years
      (range 19-43). Controls consisted of 273 women who delivered without further
      complications after 37 weeks gestation. The range values of IL-6, IL-8, and TNF
      alpha in the control group were 4.9-2620 pg/mL, 36.2-5843 pg/mL, and 8.0-28.2
      pg/mL, respectively. Patients with adverse pregnancy outcome (n = 25) were
      classified into three groups: spontaneous abortion group (n = 4), preterm
      delivery group (n = 17), and preeclampsia/eclampsia group (n = 4). There were no
      significant differences in IL-6, IL-8, and TNF-alpha between controls and study
      groups, regardless of the type of complication (p > 0.05). CONCLUSION:
      Midtrimester amniotic fluid concentrations of the proinflammatory cytokines IL-6,
      IL-8, and TNF-alpha are not predictive of adverse pregnancy outcome in terms of
      spontaneous abortion, preterm delivery or preeclampsia/eclampsia in our study
      population.

PMID- 21726174
TI  - Obesity reduces methionine sulphoxide reductase activity in visceral adipose
      tissue.
AB  - Visceral obesity is linked to insulin resistance and cardiovascular disease. A
      recent genetic study indicated that the gene locus for the anti-oxidant defense
      enzyme methionine sulphoxide reductase A (MsrA) is positively associated with the
      development of visceral adiposity. This work tested the hypothesis that Msr
      activity is diminished in visceral fat as a result of obesity. It used two animal
      models of obesity, wild-type rats fed a high-fat (45% of calories from fat) diet
      and Zucker rats fed a 10% fat calorie diet. The data indicate that MsrA activity
      was selectively reduced by ~ 25% in the visceral adipose, but not subcutaneous
      adipose or liver, of both rat models as compared to control, wild type rats
      receiving a 10% fat calorie diet. MsrB activity was similarly reduced only in
      visceral fat. The data indicate that Msr activity is reduced by obesity and may
      alter oxidative stress signalling of obesity.

PMID- 21726175
TI  - Kolaviron protects apoptotic cell death in PC12 cells exposed to atrazine.
AB  - Kolaviron (KV), a natural biflavonoid obtained from the seeds of Garcinia kola,
      has been documented for its wide pharmacological window, including anti-apoptotic
      activities. However, the underlying mechanisms are poorly understood at the
      cellular level. This study investigates the anti-apoptotic activity of KV in PC12
      cells, a rat pheochromocytoma, exposed to endocrine disruptor-atrazine (ATZ). KV
      (60 MUM) treatment for 24 h shows significant anti-apoptotic responses in PC12
      cells exposed to ATZ (232 MUM) for 24 h. KV treatment recovers the ATZ-induced
      levels of malondialdehyde, reactive oxygen species (ROS), caspase-3 activity and
      depleted levels of glutathione and catalase activity. However, KV was found to be
      ineffective to restore the ATZ-induced expression (mRNA) and activity of
      glutathione-peroxidase (GSH-Px) and glutathione reductase (GR). KV treatment also
      demonstrates significant restoration in ATZ-induced alterations in the expression
      of apoptosis markers viz., p53, Bax, Bcl2, caspase-3, caspase-9, cyclooxygenase-2
      (COX-2), c-Jun and c-fos. Flow cytometric analysis confirms the involvement of
      ROS in the mediation of ATZ-induced apoptosis in PC12 cells. Together, these data
      suggest that KV has the therapeutic potential against chemical-induced apoptotic
      cell death in the neuronal system.

PMID- 21726176
TI  - Phenolic antioxidants tert-butyl-bisphenol and vitamin E decrease oxidative
      stress and enhance vascular function in an animal model of rhabdomyolysis yet do
      not improve acute renal dysfunction.
AB  - Rhabdomyolysis (RM) caused by severe burn releases extracellular myoglobin (Mb)
      that accumulates in the kidney. Extracellular Mb is a pro-oxidant. This study
      tested whether supplementation with tert-butyl-bisphenol (BP) or vitamin E (Vit
      E, as alpha-tocopherol) at 0.12% w/w in the diet inhibits acute renal failure
      (ARF) in an animal model of RM. After RM-induction in rats, creatinine clearance
      decreased (p < 0.01), proteinuria increased (p < 0.001) and renal-tubule damage
      was detected. Accompanying ARF, biomarkers of oxidative stress (lipid oxidation
      and hemeoxygenase-1 (HO-1) gene and protein activity) increased in the kidney (p
      < 0.05). Supplemented BP or Vit E decreased lipid oxidation (p < 0.05) and HO-1
      gene/activity and restored aortic cyclic guanylyl monophosphate in control
      animals (p < 0.001), yet ARF was unaffected. Antioxidant supplementation
      inhibited oxidative stress, yet was unable to ameliorate ARF in this animal model
      indicating that oxidative stress in kidney and vascular cells may not be causally
      related to renal dysfunction elicited by RM.

PMID- 21726177
TI  - Prevalence of human papillomavirus (HPV) types in cervical cancer 2003-2008 in
      Stockholm, Sweden, before public HPV vaccination.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is the major cause of cervical
      cancer, but the prevalence of different HPV types varies depending on
      geographical location and may change dramatically after introduction of HPV
      vaccination. Here, we aimed to gain some information regarding the recent
      prevalence of different HPV types, in cancer of the uterine cervix in the
      Stockholm region, before the introduction of public HPV vaccination in Sweden.
      MATERIAL AND METHODS: From 215 diagnosed cervical cancer patients 2003-2008 at
      the Karolinska University Hospital, 160 pretreatment cervical cancer samples,
      including both squamous cell carcinomas (SCC) and adenocarcinomas (ADC) could be
      obtained. DNA was extracted from 154/160 of the SCC and ADC samples and assayed
      by Luminex Multiplex for 24 different HPV types, including 15 high-risk (HR),
      three putative HR and six low-risk types (LR). RESULTS: We successfully analysed
      154/215 (71.6%) of the locally diagnosed cases and found a high prevalence of HPV
      with 92.9% in all uterine cervix cancer cases, and 93.3% and 91.4 % in SCC and
      ADC, respectively. All HPV positive cases harboured HR types, either alone or as
      multiple infections. In SCC HPV16 dominated and together with HPV18 accounted for
      69.7% of the cases, followed in prevalence by HPV33, 31 and 45. In ADC, HPV18 was
      more common than HPV16, and they were observed in all except one of the HPV
      positive samples. CONCLUSION: The prevalence of HPV16 and 18, followed by HPV33,
      31 and 45 is high in SCC and ADC in the Stockholm region. Public HPV vaccination
      could potentially inhibit a large proportion of such tumours underlining the
      urgency to initiate HPV vaccination.

PMID- 21726178
TI  - Efficacy of re-challenging metastatic renal cell carcinoma with mTOR inhibitors.

PMID- 21726179
TI  - Historical notes on immaturity. Part 2: surviving against the odds.
AB  - Survivors of immaturity of outstanding intelligence include Fortunio Licetus,
      born in 1577, and Isaac Newton, born in 1643. Reliable descriptions began
      appearing around 1820, and over a dozen infants were born weighing under 1000 g
      and before World War II, who developed normally. From 1876 to 2006, the birth
      weight at which half of the infants survived dropped from 2200 to 600 g.
      Statistics depended on how abortion, stillbirth and live birth were defined,
      which differed greatly from country to country. WHO definitions in 1993 required
      the registration of all infants weighing 500 g (22 complete weeks) or above. This
      definition was not universally adopted, resulting in considerable underreporting.
      Many medical societies issued ethical recommendations concerning the obligatory
      or optional treatment of immature infants. The "window", at which treatment is
      optional has been set at 22-23 weeks (Japan, Germany), 23-24 weeks (UK, USA,
      Canada), or 24-26 weeks (France, Netherlands, Switzerland). Instead of assessing
      an infant's individual prognosis, and ignoring its gender, co-morbidities, and
      particular cause of premature delivery, these rules frequently relied on
      gestational age alone to initiate or withhold life support.

PMID- 21726180
TI  - Historical notes on immaturity. Part 1: measures of viability.
AB  - The interest in the limit of viability originated from various sources, including
      legal requirements, the rejection of mechnical life support, competition for
      resources, concerns about handicaps, and proximity to the fetus with its limited
      rights. Gestational age was determined from menstrual history by Hippocratic
      writers, who established the tenacious idea that 7-, but not 8-month infants
      could survive. Naegele's rule, already published by Boerhaave in 1744, was
      correct when applied to the last day of menstruation. Birth weight and length
      were not measured until the end of the 18(th) century. This remarkable
      disinterest resulted from superstition, grossly inaccurate measurements by the
      authorities Mauriceau and Smellie, and the conversion chaos of the pre-metric
      era. A table is provided with historic mass and length units allowing to
      determine birth weight and body length in the older literature. The idea of
      viability is a remnant of vitalism, a medical doctrine popularized in 1780 by
      Brown. Many short-lived statements defined its limit, but until now what was
      meant by viability remained nebulous.

PMID- 21726181
TI  - Skin conductance indices discriminate nociceptive responses to acute stimuli from
      different heel prick procedures in infants.
AB  - AIM: To evaluate the ability of SC indexes in discriminating acute responses to
      different heel prick procedures. METHODS: Observational cohort study of a
      systematic, convenience sample of neonates with clinical indication of capillary
      blood sampling by heel prick, either for glycaemia or for blood gas analysis. The
      Neonatal Infant Pain Scale (NIPS) was used to confirm the painful nature of the
      stimuli. NIPS assessment and SC measurement (Med-Storm Pain Monitor(TM)) were
      simultaneously performed by two independent observers before, during and after
      blood sampling. RESULTS: Sixty-eight heel prick procedures (46 for glycaemia and
      22 for blood gas analysis) were applied to 16 infants. Both NIPS scores and SC
      peaks/s index were significantly higher during blood sampling than before or
      thereafter (Wilcoxon Signed Ranks, p < 0.001). There was no significant
      difference in NIPS score and SC peaks/s between the different heel prick
      procedures. Significantly higher SC area under low peaks index (Mann-Whitney, p =
      0.001) and lower SC average rise time index (Mann-Whitney, p = 0.037) were
      registered when blood was drawn for blood gas analysis than for glycaemia,
      related to a sustained acute nociceptive response to a more prolonged stimulus.
      CONCLUSION: Using the conjunction of available SC indices, SC seems able to
      differentiate the nociceptive response to acute pain of different durations.

PMID- 21726182
TI  - Effects of environmental lead exposure on T-helper cell-specific cytokines in
      children.
AB  - Lead (Pb) may alter T-lymphocyte reactivity in situ by preferentially enhancing
      the development of T-helper 2 (T(H)2)- and inhibiting T(H)1-lymphocyte
      development. These effects could result in dysregulation of the
      presence/availability of T(H)1- and T(H)2-associated cytokines. The aim of this
      study was two-fold, that is, to assess whole blood Pb levels in schoolchildren
      from Taiwanese communities that varied in degree of potential for Pb exposure and
      then ascertain if there were relationships between Pb exposure and changes in
      levels of key T(H)1 and T(H)2 cytokines. Grades 5 and 6 students were selected
      from four different community schools, i.e., one from: urban area with new homes;
      urban area with old homes; rural site with old homes; and area located near an
      oil refinery. Students at each site were further divided into healthy and
      respiratory allergy subgroups. Blood was collected and whole blood Pb levels and
      serum interferon (IFN)-gamma, interleukin (IL)-12, -4, and -5 levels were
      determined. The results indicate no differences in whole blood Pb levels (<4
      ug/dl) among students from urban and rural sites; these values were similar in
      the healthy and allergic subjects. Serum T(H)1 and T(H)2 cytokine levels also did
      not differ among/within the groups. In contrast, refinery children had
      significantly increased Pb levels (5.2-8.8 ug/dl) relative to any of the other
      sets' levels. Of these, children with allergies had serum T(H)2 cytokine levels
      significantly higher and T(H)1 cytokine levels significantly lower than their
      healthy counterparts. Oddly, though having elevated Pb levels, healthy refinery
      students did not display altered T(H)1 or T(H)2 cytokine levels relative to
      control student values. From this, we conclude that substantively increased whole
      blood Pb levels may promote T(H) cell dysregulation and alter the availability of
      key T(H)1 and T(H)2 cytokines, effects that could ultimately contribute to
      development of pulmonary allergic diseases.

PMID- 21726183
TI  - Present situation of the development of cellular-type hemoglobin-based oxygen
      carrier (hemoglobin-vesicles).
AB  - Many researchers have tested a hemoglobin (Hb) solution as a possible oxygen
      carrier after discovering that one Hb molecule contains four hemes that bind and
      release oxygen reversibly, and that blood type antigens are expressed on the
      surface of red blood cells (RBCs). However, various side effects emerged during
      the long development of Hb-based oxygen carriers (HBOCs). The physiological
      significance of the RBC structure is undergoing reconsideration. Fundamentally,
      excessive native Hb molecules are toxic, but encapsulation can shield this toxic
      effect. So-called liposomeencapsulated Hb or Hb-vesicles that mimic the cellular
      structure of RBCs have been developed for clinical applications.

PMID- 21726184
TI  - Practical considerations in the development of hemoglobin-based oxygen
      therapeutics.
AB  - The development of hemoglobin based oxygen therapeutics (HBOCs) requires
      consideration of a number of factors. While the enabling technology derives from
      fundamental research on protein biochemistry and biological interactions,
      translation of these research insights into usable medical therapeutics demands
      the application of considerable technical expertise and consideration and
      reconciliation of a myriad of manufacturing, medical, and regulatory
      requirements. The HBOC development challenge is further exacerbated by the
      extremely high intravenous doses required for many of the indications
      contemplated for these products, which in turn implies an extremely high level of
      purity is required. This communication discusses several of the important product
      configuration and developmental considerations that impact the translation of
      fundamental research discoveries on HBOCs into usable medical therapeutics.

PMID- 21726185
TI  - Systems biology of HBOC-induced vasoconstriction.
AB  - Vasoconstriction is a major adverse effect of HBOCs. The use of a single drug for
      attenuating HBOC-induced vasoconstriction has been tried with limited success.
      Since HBOC causes disruptions at multiple levels of organization in the vascular
      system, a systems approach is helpful to explore avenues to counteract the
      effects of HBOC at multiple levels by targeting multiple sites in the system. A
      multi-target approach is especially appropriate for HBOC-induced
      vasoconstriction, because HBOC disrupts the cascade of amplification by NO-cGMP
      signaling and protein phosphorylation, ultimately resulting in vasoconstriction.
      Targeting multiple steps in the cascade may alter the overall gain of
      amplification, thereby limiting the propagation of disruptive effects through the
      cascade. As a result, targeting multiple sites may accomplish a relatively high
      overall efficacy at submaximal drug doses. Identifying targets and doses for
      developing a multi-target combination HBOC regimen for oxygen therapeutics
      requires a detailed understanding of the systems biology and phenotypic
      heterogeneity of the vascular system at multiple layers of organization, which
      can be accomplished by successive iterations between experimental studies and
      mathematical modeling at multiple levels of vascular systems and organ systems.
      Towards this goal, this article addresses the following topics: a) NO-scavenging
      by HBOC, b) HBOC autoxidation-induced reactive oxygen species generation and
      endothelial barrier dysfunction, c) NO- cGMP signaling in vascular smooth muscle
      cells, d) NO and cGMP-dependent regulation of contractile filaments in vascular
      smooth muscle cells, e) phenotypic heterogeneity of vascular systems, f) systems
      biology as an approach to developing a multi-target HBOC regimen.

PMID- 21726186
TI  - Adverse HBOC-endothelial dysfunction synergism: a possible contributor to adverse
      clinical outcomes?
AB  - Adverse outcomes in clinical trials on Hemoglobin Based Oxygen Carriers (HBOCs)
      appear to have occurred more frequently in HBOC treated than in control treated
      subjects. The differential may be related to many factors, including study
      complexity and compliance issues. Adverse outcomes also appear to be related to
      chronic comorbidities in subjects undergoing elective surgery. Frequently
      occurring comorbidities in these populations are those related to aging,
      cardiovascular and metabolic disease (hypertension, atherosclerosis, diabetes,
      etc.). These are highly prevalent among many population subsets. These conditions
      have been extensively studied and are characterized by dysfunction of important
      endothelial vasoregulatory mechanisms, including impaired nitric oxide
      bioavailability, excessive generation of reactive oxygen species (ROS) and
      possibly enhanced vasoconstrictor mechanisms. Although less extensively studied,
      HBOCs have properties that may have an important amplifying effect upon
      mechanisms operating in endothelial dysfunction, by scavenging nitric oxide,
      generating further excess of ROS which in turn react with nitric oxide, inhibit
      nitric oxide synthase and possibly stimulate the release of vasoconstrictors such
      as endothelin. It is likely that amplification of vasoconstrictor effects is not
      uniformly operative in all vascular beds, and that some protective autoregulatory
      mechanisms maintain sufficient blood flow in vital organs as long as sufficient
      vasodilator reserve is available. When the latter is exhausted in the presence of
      arterial disease with physical obstructions, blood flow to vital organs may
      become compromised. This paper suggests avenues of further exploration to
      elucidate whether the combination of HBOC and endothelial dysfunction is a
      contributing factor in HBOC related adverse outcomes.

PMID- 21726187
TI  - Kinetic and thermodynamic approaches to the drug targeting phenomena.
AB  - The effectiveness of many promising drug candidates (e.g. anticancer agents)
      awaits the development of drug forms capable of delivery of their drug load
      specifically to particular sites of an organism or a cell. To make universal and
      efficient drug carriers, administered drug-loaded vehicles should be able to
      reach the pathologic zone, recognize and bind their targets at a therapeutic
      concentration before clearance from the organism. Numerous methods have been
      developed to couple drug vehicles with active targeting substances - including
      monoclonal antibodies and substrates or ligands for pathologic cell receptors.
      Other approaches have included the use of such factors as decreased pH and
      elevated activity of enzymes in tumor tissues and the hypoxic environment inside
      the tumor core. This review makes an attempt to analyze the main factors that
      influence targeting on the kinetic or thermodynamic level that may provide the
      basis for a strategy to develop and improve drug delivery systems.

PMID- 21726188
TI  - Rheological approach to targeting phenomena of lipoplexes.
AB  - Lipoplexes, the complexes of plasmid DNA with cationic lipids, are considered as
      an attractive alternative to viral delivery systems. However, synthesized
      lipoplexes showed several limitations including insufficient transfection, low
      reproducibility and low stability. Here we attempt to delineate the relationships
      between the synthesis process, morphology (e.g., shape and liquid crystal
      structure), and the transfection efficiency of lipoplexes with rheological
      technology. Mini-capillary viscometers with automatic measurement and control
      components were designed and used to study the morphology of lipoplexes at a
      macroscopical scale. In such a dilute macromolecule suspension system, the shape
      factor of lipoplex was correlated with the viscosity measurement. The results
      showed that the shape factors of lipoplexes were different with various molecular
      structures of cationic lipid and helper lipid. A quantitative relation was set up
      between the shape factors and the length of DNA/polyelectrolytes, which may help
      better explain lipoplexes formation. To improve the stability and reproducibility
      of lipoplexes, an incubation period was suggested before the use of lipoplex. A
      rheological method was introduced to fix the hydromechanical parameters so that
      the entire preparation and incubation process was carried out consistently. A
      laminar flow incubation environment was showed suitable for lipoplex preparation
      and helped improve lipoplex stability and minimize aggregation. Other flow
      incubations, such as turbulent flow or impinging flow, were more complicated and
      further study is necessary to fully understand them. In brief, the rheological
      methods can help reveal the mechanisms of lipoplex formation and advance the
      rational design of lipoplexes for pharmaceutical applications.

PMID- 21726189
TI  - Physicochemical properties of pDNA/chitosan complexes as gene delivery systems.
AB  - Successful gene therapy depends on the development of effective gene carriers.
      Naturally occurring chitosan has been employed widely as a non-viral gene carrier
      because of its low toxicity, low immunogenicity, biocompatibility, and
      biodegradability. In this review, we summarize the utilization of chitosan,
      modified chitosan, and chitosan-containing ternary complexes as gene carriers. In
      particular, we discuss the influence of the physicochemical features of
      pDNA/chitosan complexes on their functions, such as stability and gene transfer
      into cells.

PMID- 21726191
TI  - High content pharmacophores from molecular fields: a biologically relevant method
      for comparing and understanding ligands.
AB  - The question of how and why a small molecule binds to a protein is central to
      ligand-based drug discovery. The traditional way of approaching these questions
      is pharmacophore analysis. However, pharmacophores as usually applied lack
      quantitation and subtlety. An improvement is to consider the electrostatic and
      steric fields of the ligand directly. Molecular fields provide a rich view of the
      potential interactions that a molecule can make and can be validated through
      experimental data on molecular interactions and through quantum mechanics
      calculations. A technique is presented in this review for comparing molecules
      using molecular fields and assigning similarity scores. This high information
      content method can be used to align molecules for SAR analysis, to determine the
      bioactive conformation from ligand data, and to screen large libraries of
      compounds for structurally unrelated actives. An extension to allow interactive
      exploration of chemistry space via bioisostere analysis is also reviewed.
      Examples from the literature showing the success of these methods are presented,
      and future directions discussed.

PMID- 21726192
TI  - Receptor-based pharmacophore and pharmacophore key descriptors for virtual
      screening and QSAR modeling.
AB  - The intuitive nature of the pharmacophore concept has made it widely accepted by
      the medicinal chemistry community, evidenced by the past 3 decades of development
      and application of computerized pharmacophore modeling tools. On the other hand,
      shape complementarity has been recognized as a critical factor in molecular
      recognition between drugs and their receptors. Recent development of fast and
      accurate shape comparison tools has facilitated the wide spread use of shape
      matching technologies in drug discovery. However, pharmacophore and shape
      technologies, if used separately, often lead to high false positive rate. Thus,
      integrating pharmacophore matching and shape matching technologies into one
      program has the potential to reduce the false positive rates in virtual
      screening. Other issues of current pharmacophore technologies include sometimes
      high false negative rate and non-quantitative prediction. In this article, we
      first focus on a recently implemented method (Shape4) that combines receptor
      based shape matching and pharmacophore comparison in a single algorithm to create
      shape pharmacophore models for virtual screening. We also examine a recent
      example that utilizes multi-complex information to develop receptor-based
      pharmacophore models that promises to reduce false negative rate. Finally, we
      review several methods that employ receptor-based pharmacophore map and
      pharmacophore key descriptors for QSAR modeling. We conclude by emphasizing the
      concept of receptor-based shape pharmacophore and its roles in future drug
      discovery.

PMID- 21726193
TI  - New features that improve the pharmacophore tools from Accelrys.
AB  - Generating a pharmacophore is often the first step towards understanding the
      interactions between a receptor and a ligand and can be pivotal to a successful
      drug discovery project. The pharmacophore tools at Accelrys have been used to
      assist in many different projects over the years, such as lead generation,
      scaffold hopping, mining ligand databases as well as many more. In this article,
      we will review the pharmacophore tools that have been developed at Accelrys.
      These will include the often used and well validated ligand based algorithms,
      HipHop and HypoGen and as well as extensions of these algorithms, HipHopRefine
      and HypoGenRefine. Recently we also developed new pharmacophore tools in the area
      of structure based design - deriving pharmacophores from the receptor as well as
      the receptor-ligand complex - which will also be discussed in this paper.

PMID- 21726194
TI  - Simplified receptor based pharmacophore approach to retrieve potent PTP-LAR
      inhibitors using apoenzyme.
AB  - The design of biological active compounds from the apoenzyme is still a
      challenging task. Herein a simple yet efficient technique is reported to generate
      a receptor based pharmacophore solely using a ligand-free protein crystal
      structure. Human leukocyte antigen-related phosphatase (PTP-LAR) is an apoenzyme
      and a receptor like transmembrane phosphatase that has emerged as a drug target
      for diabetes, obesity and cancer. The prior knowledge of the active residues
      responsible for the mechanism of action of the protein was used to generate the
      LUDI interaction map. Then, the complement negative image of the binding site was
      used to generate the pharmacophore features. A unique strategy was followed to
      design a pharmacophore query maintaining crucial interactions with all the active
      residues, essential for the enzyme inhibition. The same query was used to screen
      several databases consisting of the Specs, IBS, MiniMaybridge, NCI and an in
      house PTP inhibitor databases. In order to overcome the common bioavailability
      problem associated with phosphatases, the hits obtained were filtered by
      Lipinski's Rule of Five, SADMET properties and validated by docking studies in
      Glide and GOLD. These docking studies not only suggest the essential ligand
      binding interactions but also the binding patterns necessary for the LAR
      inhibition. The ligand pharmacophore mapping studies further validated the
      screened protocol and supported that the final screened molecules, presumably,
      showed potent inhibitory activity. Subsequently, these molecules were subjected
      to Derek toxicity predictions and nine new molecules with different scaffold were
      obtained as non-toxic PTP-LAR inhibitors. The present prospective strategy is a
      powerful technique to identify potent inhibitors using the protein 3D structure
      alone and is a valid alternative to other structure-based and random docking
      approaches.

PMID- 21726195
TI  - Pharmacophore modeling in drug design: recent advances.

PMID- 21726196
TI  - Varying dependency of periplasmic peptidylprolyl cis-trans isomerases in
      promoting Yersinia pseudotuberculosis stress tolerance and pathogenicity.
AB  - Periplasmic PPIases (peptidylprolyl cis-trans isomerases) catalyse the cis-trans
      isomerization of peptidyl-prolyl bonds, which is a rate-limiting step during
      protein folding. We demonstrate that the surA, ppiA, ppiD, fkpA and fklB alleles
      each encode a periplasmic PPIase in the bacterial pathogen Yersinia
      pseudotuberculosis. Of these, four were purified to homogeneity. Purified SurA,
      FkpA and FklB, but not PpiD, displayed detectable PPIase activity in vitro.
      Significantly, only Y. pseudotuberculosis lacking surA caused drastic alterations
      to the outer membrane protein profile and FA (fatty acid) composition. They also
      exhibited aberrant cellular morphology, leaking LPS (lipopolysaccharide) into the
      extracellular environment. The SurA PPIase is therefore most critical for
      maintaining Y. pseudotuberculosis envelope integrity during routine culturing. On
      the other hand, bacteria lacking either surA or all of the genes ppiA, ppiD, fkpA
      and fklB were sensitive to hydrogen peroxide and were attenuated in mice
      infections. Thus Y. pseudotuberculosis exhibits both SurA-dependent and 
      independent requirements for periplasmic PPIase activity to ensure in vivo
      survival and a full virulence effect in a mammalian host.

PMID- 21726197
TI  - Reconstitution in liposomes of the functionally active human OCTN1 (SLC22A4)
      transporter overexpressed in Escherichia coli.
AB  - The hOCTN1 (human organic cation transporter 1) overexpressed in Escherichia coli
      and purified by Ni-chelating chromatography has been reconstituted in liposomes
      by detergent removal with a batch-wise procedure. The reconstitution was
      optimized with respect to the protein concentration, the detergent/phospholipid
      ratio and the time of incubation with Amberlite XAD-4 resin. Time-dependent
      [(14)C]tetraethylammonium, [(3)H]carnitine or [(3)H]ergothioneine uptake was
      measured in proteoliposomes with activities ratios of 8:1.3:1 respectively.
      Optimal activity was found at pH 8.0. The transport depended on intraliposomal
      ATP. [(14)C]tetraethylammonium transport was inhibited by several compounds. The
      most effective were acetyl-choline and gamma-butyrobetaine, followed by
      acetylcarnitine and tetramethylammonium. Reagents such as pyridoxal 5-phosphate,
      MTSES [sodium (2-sulfonatoethyl) methanethiosulfonate] and mercurials strongly
      inhibited the transport. From kinetic analysis of tetraethylammonium transport a
      K(m) of 0.77 mM was calculated. Acetylcholine and gamma-butyrobetaine behaved as
      competitive inhibitors of TEA (tetraethylammonium) transport with K(i) values of
      0.44 and 0.63 mM respectively.

PMID- 21726198
TI  - Targeting the regulation of CFTR channels.
AB  - In this issue of the Biochemical Journal, Zhang et al. reveal a new strategy for
      modifying the regulated function of CFTR (cystic fibrosis transmembrane
      conductance regulator) on the apical surface of epithelial cells. Simply stated,
      these authors tested the idea that the cAMP-dependent channel activity of CFTR
      could be effectively enhanced by disruption of a protein-protein interaction
      which is normally inhibitory for the production of cAMP. This particular protein
      protein interaction [between the PDZ motif of LPA2 (type 2 lysophosphatidic acid
      receptor) and the scaffold protein Nherf2 (Na+/H+ exchanger regulatory factor 2)]
      is localized in the CFTR interactome on the apical membrane of epithelial cells.
      Hence disruption of the LPA2-Nherf2 interaction should lead to a localized
      elevation in cAMP and, consequently, increased cAMP-dependent CFTR activity on
      the surface of epithelial cells. Zhang et al. confirmed these expectations for a
      small-molecule compound targeting the LPA2-Nherf2 interaction using relevant
      cultures and tissues thought to model the human respiratory epithelium. The
      success of this strategy depended on previous knowledge regarding the role for
      multiple PDZ-motif-mediated interactions in signalling (directly or indirectly)
      to CFTR. Given the number and diversity of such PDZ-mediated interactions, future
      structural and computational studies will be essential for guiding the design of
      specific pharmacological interventions.

PMID- 21726199
TI  - Assessing mitochondrial dysfunction in cells.
AB  - Assessing mitochondrial dysfunction requires definition of the dysfunction to be
      investigated. Usually, it is the ability of the mitochondria to make ATP
      appropriately in response to energy demands. Where other functions are of
      interest, tailored solutions are required. Dysfunction can be assessed in
      isolated mitochondria, in cells or in vivo, with different balances between
      precise experimental control and physiological relevance. There are many methods
      to measure mitochondrial function and dysfunction in these systems. Generally,
      measurements of fluxes give more information about the ability to make ATP than
      do measurements of intermediates and potentials. For isolated mitochondria, the
      best assay is mitochondrial respiratory control: the increase in respiration rate
      in response to ADP. For intact cells, the best assay is the equivalent
      measurement of cell respiratory control, which reports the rate of ATP
      production, the proton leak rate, the coupling efficiency, the maximum
      respiratory rate, the respiratory control ratio and the spare respiratory
      capacity. Measurements of membrane potential provide useful additional
      information. Measurement of both respiration and potential during appropriate
      titrations enables the identification of the primary sites of effectors and the
      distribution of control, allowing deeper quantitative analyses. Many other
      measurements in current use can be more problematic, as discussed in the present
      review.

PMID- 21726200
TI  - Transcriptional regulation of the intestinal luminal Na+ and Cl- transporters.
AB  - The epithelial apical membrane Na+/H+ exchangers [NHE (sodium hydrogen
      exchanger)2 and NHE3] and Cl-/HCO3- exchangers [DRA (down-regulated in adenoma)
      and PAT-1 (putative anion transporter 1)] are key luminal membrane transporters
      involved in electroneutral NaCl absorption in the mammalian intestine. During the
      last decade, there has been a surge of studies focusing on the short-term
      regulation of these electrolyte transporters, particularly for NHE3 regulation.
      However, the long-term regulation of the electrolyte transporters, involving
      transcriptional mechanisms and transcription factors that govern their basal
      regulation or dysregulation in diseased states, has only now started to unfold
      with the cloning and characterization of their gene promoters. The present review
      provides a detailed analysis of the core promoters of NHE2, NHE3, DRA and PAT-1
      and outlines the transcription factors involved in their basal regulation as well
      as in response to both physiological (butyrate, protein kinases and probiotics)
      and pathophysiological (cytokines and high levels of serotonin) stimuli. The
      information available on the transcriptional regulation of the recently
      identified NHE8 isoform is also highlighted. Therefore the present review bridges
      a gap in our knowledge of the transcriptional mechanisms underlying the
      alterations in the gene expression of intestinal epithelial luminal membrane Na+
      and Cl- transporters involved in electroneutral NaCl absorption. An understanding
      of the mechanisms of the modulation of gene expression of these transporters is
      important for a better assessment of the pathophysiology of diarrhoea associated
      with inflammatory and infectious diseases and may aid in designing better
      management protocols.

PMID- 21726201
TI  - Aminoaciduria, but normal thyroid hormone levels and signalling, in mice lacking
      the amino acid and thyroid hormone transporter Slc7a8.
AB  - LAT2 (system L amino acid transporter 2) is composed of the subunits Slc7a8/Lat2
      and Slc3a2/4F2hc. This transporter is highly expressed along the basolateral
      membranes of absorptive epithelia in kidney and small intestine, but is also
      abundant in the brain. Lat2 is an energy-independent exchanger of neutral amino
      acids, and was shown to transport thyroid hormones. We report in the present
      paper that targeted inactivation of Slc7a8 leads to increased urinary loss of
      small neutral amino acids. Development and growth of Slc7a8(-/-) mice appears
      normal, suggesting functional compensation of neutral amino acid transport by
      alternative transporters in kidney, intestine and placenta. Movement co
      ordination is slightly impaired in mutant mice, although cerebellar development
      and structure remained inconspicuous. Circulating thyroid hormones, thyrotropin
      and thyroid hormone-responsive genes remained unchanged in Slc7a8(-/-) mice,
      possibly because of functional compensation by the thyroid hormone transporter
      Mct8 (monocarboxylate transporter 8), which is co-expressed in many cell types.
      The reason for the mild neurological phenotype remains unresolved.

PMID- 21726202
TI  - Natural killer cell subsets in man and rodents.
AB  - NK cells are important contributors to the early immune defence against infected
      or transformed cells. They are rapidly activated in response to cytokines,
      whereby they exert their effector functions. NK cell responses are controlled by
      a multitude of receptors, which are expressed by subpopulations of NK cells with
      distinct phenotypes and functionalities. Direct comparisons between species are
      often difficult because of differences in the expression of NK cell receptors and
      other markers. In addition, NK cells change their phenotype and effector
      functions during differentiation, by tissue-specific factors, or upon activation,
      complicating interpretations. We will here review the similarities and
      differences between the major NK cell subsets in man and two well-characterized
      rodent models.

PMID- 21726203
TI  - Plasma soluble HLA-G is a potential biomarker for diagnosis of colorectal,
      gastric, esophageal and lung cancer.
AB  - Human leukocyte antigen-G (HLA-G) is a novel tumor marker and its soluble
      isoforms produce secretory proteins. Increased soluble HLA-G (sHLA-G) levels have
      been reported in patients with melanoma, neuroblastoma, lymphoproliferative
      disorders, breast, ovarian and colorectal carcinoma when compared to healthy
      controls or subjects with benign neoplasms. The aim of this study is to
      investigate whether or not plasma sHLA-G can be used as a potential biomarker for
      cancer diagnosis. We measured plasma sHLA-G levels in 166 patients with early
      stages of colorectal cancer (CRC, n = 37), gastric cancer (GC, n = 28),
      esophageal squamous cell carcinoma (ESCC, n = 58) and non-small cell lung cancer
      (NSCLC, n = 43), and compared them to healthy controls (n = 260) by using a
      specific HLA-G enzyme-linked immunosorbent assay (ELISA). We found that plasma
      sHLA-G levels were significantly higher in cancer patients than in healthy
      controls (all P < 0.0001). The areas under the receiver-operating characteristic
      (ROC) curves for sHLA-G were 0.97, 0.91, 0.98 and 0.80 for healthy controls vs
      CRC, GC, ESCC and NSCLC, respectively. At 100% specificity, the highest
      sensitivity achieved to detect CRC, GC, ESCC and NSCLC was 94% [95% confidence
      interval (CI), 89-99], 85% (95% CI, 76-94), 91% (95% CI, 88-94) and 51% (95% CI,
      43-59) at a cutoff value of 49 U/ml, respectively. These findings suggest that
      plasma sHLA-G may be a useful molecule in the differential diagnosis of these
      malignancies against healthy controls.

PMID- 21726204
TI  - KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic
      leukemia and the clinical course of disease.
AB  - The aim of this study was to analyze the association between gene polymorphisms
      of killer-cell immunoglobulin-like receptors (KIRs) and their human leukocyte
      antigen (HLA) ligands and susceptibility to B-cell chronic lymphocytic leukemia
      (B-CLL) and the clinical course of disease. The distribution of individual KIR
      genes in 197 B-CLL patients and 200 controls was similar, except for a tendency
      for lower frequencies of the KIR2DS3 and KIR2DL5 genes among B-CLL patients
      (26.9% vs 35.5%, P = 0.06, 46.2% vs 55.5%, P = 0.06). The associations between
      KIR2DS3 and B-CLL reached statistical significance in women (P = 0.05). Moreover,
      we found a trend toward a lower frequency of genotypes with the presence of five
      or six activating KIR genes in B-CLL patients compared to controls (20.8% vs
      29.0%, P = 0.06), and a significantly higher frequency of individuals possessing
      genotypes with a prevalence of inhibitory over activating KIR genes (ratio <
      0.71) among B-CLL patients (P = 0.04). The HLA-Bw4 specificity was significantly
      reduced among B-CLL patients (48.7% vs 63.0%, P = 0.005), which resulted from a
      decreased frequency of HLA-Bw4(Thr80) (21.6% vs 32.0%, P = 0.02). Moreover, among
      HLA-Bw4-positive individuals, progression-free survival (PFS) tended to be higher
      in the presence of KIR3DS1 (77% +/- 9% vs 39% +/- 13%, P = 0.07). However, in B
      CLL patients, the presence of HLA-C2 was associated with decreased PFS (49% +/-
      9% vs 75% +/- 7%, P = 0.02), and among HLA-C2-positive patients, the probability
      of PFS was significantly reduced in the absence of KIR2DS1 (34% +/- 11% vs 77% +/
      7%, P = 0.007). Our results indicate that the pattern of inhibitory/activating
      KIR genes, together with their HLA ligands, is associated with susceptibility to
      B-CLL and affects the clinical course of this disease.

PMID- 21726205
TI  - A novel HLA-DRB1 allele: DRB1*15:02:08.
AB  - The HLA-DRB1* 15:02:08 allele differs from the closest allele HLA-DRB1* 15:02:01
      by a single synonymous nucleotide change at position 116 in exon 2 from C to T.

PMID- 21726206
TI  - Milestones in umbilical cord blood transplantation.
AB  - Much has been learned about umbilical cord blood (UCB) since the first human cord
      blood transplant was performed back in 1988. Cord blood banks have been
      established worldwide for the collection, cryopreservation and distribution of
      UCB for allogeneic haematopoietic stem cell transplantation. UCB has now become
      one of the most commonly used sources of haematopoietic stem cells for allogeneic
      transplantation. Today, a global network of cord blood banks and transplant
      centres has been established with a large common inventory, allowing for more
      than 20000 transplants worldwide in children and adults with severe
      haematological diseases. Several studies have been published on UCB transplant,
      assessing risk factors such as cell dose and human leucocyte antigen mismatch.
      New strategies are ongoing to facilitate engraftment and reduce transplant
      related mortality and include the use of reduced-intensity conditioning regimen,
      intra-bone injection of cord blood cells, double cord blood transplants or ex
      vivo expansion of cord blood cells. The absence of ethical concern and the
      unlimited supply of cells explain the increasing interest of using UCB for
      developing regenerative medicine.

PMID- 21726207
TI  - The challenge of haemoglobinopathies in resource-poor countries.
AB  - The haemoglobinopathies, inherited disorders of the structure or synthesis of
      haemoglobin, are the commonest monogenic diseases. Approximately 80% of the
      annual births of babies with these conditions occur in low-or middle-income
      countries, many of which have extremely limited facilities for their control and
      management. Given that the population size of many of them is growing and, as
      social and public health facilities improve, increasing numbers of these babies
      will survive to present for diagnosis and treatment. Hence, the
      haemoglobinopathies will constitute an increasing global health burden. Hitherto,
      they have been largely ignored by governments of high-frequency countries and by
      the international health agencies. However, a start has been made in developing
      control programmes in some low-income countries and there is already considerable
      evidence that much can be done to improve the situation by the development of
      partnerships between groups in richer countries and centres in low-income
      countries. The natural extension of this approach is the further development of
      partnerships between countries where expertise in this field has been developed
      and adjacent countries where no such expertise exists. It is vital that the
      haematology community of the richer countries becomes involved in programmes of
      this type while, at the same time, putting pressure on their governments and on
      international health agencies for support for this work. 

PMID- 21726208
TI  - Haematology in Africa.

PMID- 21726209
TI  - Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, protects
      dopaminergic neurons from neurotoxin-induced damage.
AB  - BACKGROUND AND PURPOSE: Prevention or disease-modifying therapies are critical
      for the treatment of neurodegenerative disorders such as Alzheimer's disease,
      Parkinson's disease and Huntington's disease. However, no such intervention is
      currently available. Growing evidence has demonstrated that administration of
      histone deacetylase (HDAC) inhibitors ameliorates a wide range of neurologic and
      psychiatric disorders in experimental models. Suberoylanilide hydroxamic acid
      (SAHA) was the first HDAC inhibitor approved by the Food and Drug Administration
      for the sole use of cancer therapy. The purpose of this study was to explore the
      potential new indications of SAHA for therapy of neurodegenerative diseases in in
      vitro Parkinson's disease models. EXPERIMENTAL APPROACH: Mesencephalic neuron
      glia cultures and reconstituted cultures were used to investigate neurotrophic
      and neuroprotective effects of SAHA. We measured toxicity in dopaminergic
      neurons, using dopamine uptake assay and morphological analysis and expression of
      neurotrophic substances by enzyme-linked immunosorbent assay and real-time RT
      PCR. KEY RESULTS: In mesencephalic neuron-glia cultures, SAHA displayed dose- and
      time-dependent prolongation of the survival and protection against neurotoxin
      induced neuronal death of dopaminergic neurons. Mechanistic studies revealed that
      the neuroprotective effects of SAHA were mediated in part by promoting release of
      neurotrophic factors from astroglia through inhibition of histone deacetylation.
      CONCLUSION AND IMPLICATIONS: The novel neurotrophic and neuroprotective effects
      of SAHA demonstrated in this study suggest that further study of this HDAC
      inhibitor could provide a new therapeutic approach to the treatment of
      neurodegenerative diseases.

PMID- 21726210
TI  - Azithromycin distinctively modulates classical activation of human monocytes in
      vitro.
AB  - BACKGROUND AND PURPOSE: Azithromycin has been reported to modify activation of
      macrophages towards the M2 phenotype. Here, we have sought to identify the
      mechanisms underlying this modulatory effect of azithromycin on human monocytes,
      classically activated in vitro. EXPERIMENTAL APPROACH: Human blood monocytes were
      primed with IFN-gamma for 24 h and activated with LPS for 24 h. Azithromycin,
      anti-inflammatory and lysosome-affecting agents were added 2 h before IFN-gamma.
      Cytokine and chemokine expression was determined by quantitative PCR and protein
      release by ELISA. Signalling molecules were determined by Western blotting and
      transcription factor activation quantified with a DNA-binding ELISA kit. KEY
      RESULTS: Azithromycin (1.5-50 uM) dose-dependently inhibited gene expression
      and/or release of M1 macrophage markers (CCR7, CXCL 11 and IL-12p70), but
      enhanced CCL2, without altering TNF-alpha or IL-6. Azithromycin also enhanced the
      gene expression and/or release of M2 macrophage markers (IL-10 and CCL18), and
      the pan-monocyte marker CD163, but inhibited that of CCL22. The Toll-like
      receptor (TLR) 4 signalling pathway was modulated, down-regulating NF-kappaB and
      STAT1 transcription factors. The inhibitory profile of azithromycin differed from
      that of dexamethasone, the phosphodiesterase-4 inhibitor roflumilast and the p38
      kinase inhibitor SB203580 but was similar to that of the lysosomotropic drug
      chloroquine. Effects of concanamycin and NH4Cl, which also act on lysosomes,
      differed significantly. CONCLUSIONS AND IMPLICATIONS: Azithromycin modulated
      classical activation of human monocytes by inhibition of TLR4-mediated signalling
      and possible effects on lysosomal function, and generated a mediator expression
      profile that differs from that of monocyte/macrophage phenotypes so far
      described.

PMID- 21726212
TI  - Successful treatment of disseminated superficial actinic porokeratosis with
      calcipotriol.

PMID- 21726211
TI  - CD4(+) T cells defined by their Vbeta T cell receptor expression are associated
      with immunoregulatory profiles and lesion size in human leishmaniasis.
AB  - Leishmaniasis is caused by infection with the protozoan parasite, Leishmania,
      that parasitizes human cells, and the cellular immune response is essential for
      controlling infection. In order to measure the host T cell response to Leishmania
      infection, we have measured the expansion, activation state and functional
      potential of specific T cells as identified by their T cell receptor Vbeta region
      expression. In a group of cutaneous leishmaniasis (CL) patients, we evaluated
      these characteristics in nine different T cell subpopulations as identified by
      their Vbeta region expression, before and after specific Leishmania antigen
      stimulation. Our results show: (1) an increase in CD4(+) T cells expressing Vbeta
      5.2 and Vbeta 24 in CL compared to controls; (2) a Leishmania antigen-induced
      increase in CD4(+) T cells expressing Vbeta 5.2, 11, 12 and 17; (3) a profile of
      previous activation of CD4(+) Vbeta 5.2-, 11- and 24-positive T cells, with
      higher expression of CD45RO, HLA-DR, interferon-gamma, tumour necrosis factor
      alpha and interleukin-10 compared to other Vbeta-expressing subpopulations; (4) a
      positive correlation between higher frequencies of CD4(+) Vbeta5.2(+) T cells and
      larger lesions; and (5) biased homing of CD4(+) T cells expressing Vbeta 5.2 to
      the lesion site. Given that CL disease involves a level of pathology (ulcerated
      lesions) and is often followed by long-lived protection and cure, the
      identification of specific subpopulations active in this form of disease could
      allow for the discovery of immunodominant Leishmania antigens important for
      triggering efficient host responses against the parasite, or identify cell
      populations most involved in pathology.

PMID- 21726213
TI  - Erythema gyratum repens-like eruptions with large cell transformation in a
      patient with mycosis fungoides.

PMID- 21726215
TI  - Idiopathic scrotal calcinosis: report of two cases and review of literature.

PMID- 21726216
TI  - Leprosy: forgotten, but not gone (yet).

PMID- 21726217
TI  - Assessing the incremental value of diagnostic and prognostic markers: a review
      and illustration.
AB  - BACKGROUND: New markers may improve prediction of diagnostic and prognostic
      outcomes. We review various measures to quantify the incremental value of markers
      over standard, readily available characteristics. METHODS: Widely used
      traditional measures include the improvement in model fit or in the area under
      the receiver operating characteristic (ROC) curve (AUC). New measures include the
      net reclassification index (NRI) and decision-analytic measures, such as the
      fraction of true-positive classifications penalized for false-positive
      classifications [net benefit (NB)]. For illustration, we discuss a case study on
      the presence of residual tumour vs. benign tissue in 544 patients with testicular
      cancer. We assessed three tumour markers [Alpha-fetoprotein (AFP), Human
      chorionic gonadotropin (HCG) and Lactate dehydrogenase (LDH)] for their
      incremental value over currently standard clinical predictors. RESULTS: AUC and
      R(2) values suggested adding continuous LDH and AFP whereas NB only favoured HCG
      as a potentially promising marker at a clinically defendable decision threshold
      of 20% risk. The NRI suggested reclassification potential of all three markers.
      CONCLUSIONS: The improvement in standard discrimination measures, which focus on
      finding variables that might be promising across all decision thresholds, may not
      detect the most informative markers at a specific threshold of particular
      clinical relevance. When a marker is intended to support decision-making,
      calculation of the improvement in a decision-analytic measure, such as NB, is
      preferable over an overall judgment as obtained from the AUC in ROC analysis.

PMID- 21726219
TI  - Restorative, regenerative and revelatory.

PMID- 21726218
TI  - The interleukin-17 cytokine family: critical players in host defence and
      inflammatory diseases.
AB  - The interleukin-17 (IL-17) cytokines, IL-17A to IL-17F, are emerging as critical
      players in host defence responses and inflammatory diseases. Substantial data
      support the role of these proteins in innate and adaptive immunity. Of these
      family members, IL-17A, IL-17F and IL-17E have been the best studied. Both IL-17A
      and IL-17F contribute to the host response to extracellular bacteria and fungi,
      and IL-17E has been shown to play a role in parasitic infections. In addition,
      numerous pre-clinical and clinical studies link these proteins to the
      pathogenesis of inflammatory diseases, and a number of therapeutic programmes
      targeting these family members are in clinical development. This review will
      highlight the cellular sources, receptors/target cells, and role in inflammation
      of these and the less-characterized family members, IL-17B, IL-17C and IL-17D.

PMID- 21726220
TI  - Where is dentistry in regenerative medicine?
AB  - Where does dentistry fit into the field of regenerative medicine? Based on the
      fact that the goal of regenerative medicine is to restore function to damaged
      organs and tissues, it is apparent that dentistry, which has long embraced the
      concept of restoring function of damaged teeth, has embraced this goal from the
      very beginning. In this brief review we present the opinion that if you take as
      the primary criterion the restoration of tissue and organ function, dentistry has
      not only been at the forefront of restorative medicine but actually predates it
      in practice. We illustrate the depth and breadth of dental regenerative medicine
      using examples of therapies or potential therapies from our laboratories. These
      begin with an example from a historical area of strength, dental implant design
      and fabrication, progress to a more high tech bone scaffold fabrication project,
      and finish with a stem cell-based soft tissue engineering project. In the final
      analysis we believe that the restorative nature of dentistry will keep it at the
      forefront of regenerative medicine.

PMID- 21726221
TI  - Dental caries pathogenicity: a genomic and metagenomic perspective.
AB  - In this review we address the subject of dental caries pathogenicity from a
      genomic and metagenomic perspective. The application of genomic technologies is
      certain to yield novel insights into the relationship between the bacterial
      flora, dental health and disease. Three primary attributes of bacterial species
      are thought to have direct impact on caries development, these include: adherence
      on tooth surfaces (biofilm formation), acid production and acid tolerance.
      Attempts to define the specific aetiological agents of dental caries have proven
      to be elusive, supporting the notion that caries aetiology is perhaps complex and
      multi-faceted. The recently introduced Human Microbiome Project (HMP) that
      endeavors to characterise the micro-organisms living in and on the human body is
      likely to shed new light on these questions and improve our understanding of
      polymicrobial disease, microbial ecology in the oral cavity and provide new
      avenues for therapeutic and molecular diagnostics developments.

PMID- 21726222
TI  - Regenerative endodontics in light of the stem cell paradigm.
AB  - Stem cells play a critical role in development and in tissue regeneration. The
      dental pulp contains a small sub-population of stem cells that are involved in
      the response of the pulp to caries progression. Specifically, stem cells replace
      odontoblasts that have undergone cell death as a consequence of the cariogenic
      challenge. Stem cells also secrete factors that have the potential to enhance
      pulp vascularisation and provide the oxygen and nutrients required for the
      dentinogenic response that is typically observed in teeth with deep caries.
      However, the same angiogenic factors that are required for dentine regeneration
      may ultimately contribute to the demise of the pulp by enhancing vascular
      permeability and interstitial pressure. Recent studies focused on the biology of
      dental pulp stem cells revealed that the multipotency and angiogenic capacity of
      these cells could be exploited therapeutically in dental pulp tissue engineering.
      Collectively, these findings suggest new treatment paradigms in the field of
      endodontics. The goal of this review is to discuss the potential impact of dental
      pulp stem cells to regenerative endodontics.

PMID- 21726223
TI  - Emerging technologies for the prevention of dental caries. Are current methods of
      prevention sufficient for the high risk patient?
AB  - Fluorides and chlorhexidine are technologies that are 65 and 40 years old,
      respectively. This overview argues that current methods of caries prevention are
      not effective for the high caries risk patient. In this review examples,
      arguments and recommendations are provided to address the high caries risk
      patient that include: failure of comprehensive chemical modalities treatments to
      address the high caries risk patient; ecological alteration - would this be an
      effective approach?; and biomaterials and oral microbiome research to address the
      high caries risk patient.

PMID- 21726224
TI  - Children with very early onset obsessive-compulsive disorder: clinical features
      and treatment outcome.
AB  - BACKGROUND: There is emerging evidence that early onset obsessive-compulsive
      disorder (OCD) may be a phenomenologically distinct subtype of the disorder.
      Previous research has shown that individuals who report an early onset display
      greater severity and persistence of symptoms, and they may be less responsive to
      treatment. To date, this question has been investigated solely in adult samples.
      The present study represents the first investigation into the effect of age at
      onset of OCD on clinical characteristics and response to treatment in a
      paediatric sample. METHOD: A total of 365 young people referred to a specialist
      OCD clinic were included in the study. Clinical records were used to examine
      potential differences in key clinical characteristics between those who had a
      very early onset of the disorder (before 10 years) and those who had a late onset
      (10 years or later). Group differences in treatment responsiveness were also
      examined within a subgroup that received cognitive behaviour therapy (CBT) alone
      or CBT plus medication (n = 109). RESULTS: The very early onset group were
      characterised by a longer duration of illness, higher rates of comorbid tics,
      more frequent ordering and repeating compulsions and greater parent-reported
      psychosocial difficulties. There were no differences in treatment response
      between the groups, and when age at onset was examined as a continuous variable,
      it did not correlate with treatment response. CONCLUSIONS: Very early onset OCD
      may be associated with different symptoms and comorbidities compared with late
      onset OCD. However, these differences do not appear to impact on responsiveness
      to developmentally tailored CBT alone or in combination with medication. These
      findings further indicate the value in early detection and treatment of OCD in
      childhood.

PMID- 21726226
TI  - Impact of Porphyromonas gingivalis inoculation on ligature-induced alveolar bone
      loss. A pilot study in rats.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis is a polymicrobial infection
      characterized by the loss of connective tissue attachment, periodontal ligament
      and alveolar bone. The aim of this study was to evaluate the impact of
      Porphyromonas gingivalis inoculation on the ligature-induced alveolar bone loss
      (ABL) model in rats. MATERIAL AND METHODS: Forty male Wistar rats were randomly
      assigned to the following groups: G1, control (n = 10); G2, ligature-induced ABL
      (n = 15); and G3, ligature-induced ABL + P. gingivalis inoculation (n = 15). Rats
      in G2 and G3 were killed 15, 21 and 30 d after ligature placement, and the
      following parameters were assessed: microbiological load; ABL; and interleukin
      (IL)-1beta (Il1beta)/Il1ra, Il6/Il10 and Rankl/osteoprotegerin (Opg) mRNA ratios
      in the gingival tissues, as determined by quantitative PCR. RESULTS:
      Microbiological analyses demonstrated that rats in G1, G2 and G3 were positive
      for the presence of bacteria (determined using PCR amplification of the 16S
      gene), but that only the treatment sites of rats in G3 were positive for P.
      gingivalis at all time-points investigated. Histometrically, significant bone
      loss (p<0.001) was observed for both ligated groups (G2 and G3) compared with the
      nonligated group (G1), with higher ABL observed for G2 at all the experimental
      time-points. Furthermore, gene-expression analysis demonstrated that the presence
      of P. gingivalis in the dentogingival area significantly decreased the
      Il1beta/Il1ra, Il6/Il10 and Rankl/Opg mRNA ratios compared with ligature alone.
      CONCLUSION: Within the limits of this pilot study, it was concluded that
      inoculation of P. gingivalis affected the ligature-induced ABL model by the
      induction of an anti-inflammatory and antiresorptive host response.

PMID- 21726225
TI  - Do callous-unemotional traits moderate the relative importance of parental
      coercion versus warmth in child conduct problems? An observational study.
AB  - BACKGROUND: Research suggests that parenting has little influence on the
      development of antisocial behavior in children with callous-unemotional (CU)
      traits. We aimed to extend and improve on prior studies examining the moderating
      role of CU traits on associations between parenting and conduct problems, by
      using independent observations of two key dimensions of parenting: coercion and
      warmth. METHODS: The participants included clinic-referred conduct-disordered
      boys (4-12 years; N = 95) and their families. Coercive parenting was coded from
      observations of family interaction and parental warmth was coded from Five-Minute
      Speech Samples. CU traits and conduct problems were rated by multiple informants.
      RESULTS: In both mothers and fathers, CU traits moderated links between observed
      parenting and conduct problems. Specifically, coercive parenting was more
      strongly positively associated with conduct problems in boys with lower levels of
      CU traits, whereas parental warmth was more strongly negatively associated with
      conduct problems in boys with higher levels of CU traits. CONCLUSIONS: These
      findings suggest that different dimensions of parenting may need to be targeted
      in the treatment of early onset conduct problems in children high and low on CU
      traits.

PMID- 21726227
TI  - WSAVA - a global phenomenon.

PMID- 21726228
TI  - Canine tonsillar squamous cell carcinoma -- a multi-centre retrospective review
      of 44 clinical cases.
AB  - OBJECTIVES: To review the presenting clinical signs, treatment and survival of
      dogs with tonsillar squamous cell carcinoma and, if possible, to identify useful
      prognostic indicators. METHODS: Medical records of 44 dogs were reviewed
      retrospectively. Clinical signs, clinical stage, time of diagnosis, treatment and
      outcome were recorded. Data were analysed using the Kaplan-Meier, log-rank,
      Student's t test, Kruskal-Wallis test and Chi-square/Fisher Exact test as
      appropriate. RESULTS: The most frequent clinical signs were cough (12 dogs, 27%),
      enlarged lymph nodes (11 dogs, 25%) and dysphagia (11 dogs, 25%). Anorexia and
      lethargy were less common but were significantly associated with a poor outcome.
      No matter what treatment modalities were used, survival times were short and
      median survival time for all the dogs in the study was 179 days. However, there
      were a small number of long-term survivors. CLINICAL SIGNIFICANCE: Dogs with
      tonsillar squamous cell carcinoma that suffered anorexia and lethargy had shorter
      survival times than patients without these clinical signs. Although surgery,
      chemotherapy and radiotherapy seem to increase the median survival time of dogs
      diagnosed with tonsillar squamous cell carcinoma, there is no highly effective
      treatment for canine tonsillar squamous cell carcinoma.

PMID- 21726229
TI  - Alteration in blood gases in cats naturally infected with Aelurostrongylus
      abstrusus.
AB  - Four cats were presented with respiratory signs and first-stage larvae of
      Aelurostrongylus abstrusus were found in faecal samples. Anthelmintic treatment
      was given to the infected cats and venous blood gases were analysed during the
      treatment period. Blood gas analysis suggested hypoventilation and respiratory
      acidosis in infected cats. Hypoventilation may be the result of airway
      obstruction by adults and larvae in respiratory bronchioles and the alveolar
      canals. The blood gas values had returned close to the physiological range by two
      months after treatment. Assessment of respiratory acidosis may aid development of
      additional treatment methods in cats infected with A. abstrusus.

PMID- 21726230
TI  - Use of collagen shields for treatment of chronic bilateral corneal ulcers in a
      pet rabbit.
AB  - A four-year-old, 1.3-kg entire male Holland Lop pet rabbit (Oryctolagus
      cuniculus) was presented with a two-day history of bilateral epiphora and
      blepharospasm. Fluorescein staining revealed bilateral medio-ventral corneal
      ulceration. Initial topical treatment included ophthalmic broad-spectrum
      antibiotics and artificial tear solutions. Over a six-month period, antibiotics
      were changed based on corneal culture and sensitivity test results, and periodic
      corneal debridement was performed. With little to no improvement, and recurrence
      of the previous clinical signs, surgical intervention was considered but withheld
      because of individual pet consideration and owner's reluctance. Hydrophilic
      contact lenses were placed for corneal support but failed and caused a severe
      ocular response. Corneal collagen shields were placed bilaterally in order to
      promote corneal healing. Recheck examination performed seven days after placement
      revealed complete resolution of the ulcer in one eye and major reduction of the
      corneal ulcer in the contra-lateral eye.

PMID- 21726231
TI  - Bell's palsy with concomitant idiopathic cranial nerve polyneuropathy in seven
      dogs.

PMID- 21726232
TI  - Crucial role of (homo)glutathione in nitrogen fixation in Medicago truncatula
      nodules.
AB  - Legumes form a symbiotic interaction with bacteria of the Rhizobiaceae family to
      produce nitrogen-fixing root nodules under nitrogen-limiting conditions. We
      examined the importance of glutathione (GSH) and homoglutathione (hGSH) during
      the nitrogen fixation process. Spatial patterns of the expression of the genes
      involved in the biosynthesis of both thiols were studied using promoter-GUS
      fusion analysis. Genetic approaches using the nodule nitrogen-fixing zone
      specific nodule cysteine rich (NCR001) promoter were employed to determine the
      importance of (h)GSH in biological nitrogen fixation (BNF). The (h)GSH synthesis
      genes showed a tissue-specific expression pattern in the nodule. Down-regulation
      of the gamma-glutamylcysteine synthetase (gammaECS) gene by RNA interference
      resulted in significantly lower BNF associated with a significant reduction in
      the expression of the leghemoglobin and thioredoxin S1 genes. Moreover, this
      lower (h)GSH content was correlated with a reduction in the nodule size.
      Conversely, gammaECS overexpression resulted in an elevated GSH content which was
      correlated with increased BNF and significantly higher expression of the sucrose
      synthase-1 and leghemoglobin genes. Taken together, these data show that the
      plant (h)GSH content of the nodule nitrogen-fixing zone modulates the efficiency
      of the BNF process, demonstrating their important role in the regulation of this
      process.

PMID- 21726233
TI  - Environment-dependent intralocus sexual conflict in a dioecious plant.
AB  - Intralocus sexual conflict is a form of conflict that does not involve direct
      interactions between males and females. It arises when selection on a shared
      trait with a common genetic basis differs between the sexes. Environmental
      factors, such as resource availability, may influence the expression and
      evolutionary outcome of such conflict. We quantified the genetic variance
      covariance matrix, G, for both sexes of Silene latifolia for floral and leaf
      traits, as well as the between-sex matrix, B. We also quantified selection on the
      sexes via survival for 2 yr in four natural populations that varied in water
      availability. Environment-dependent intralocus sexual conflict exists for
      specific leaf area, a trait that is genetically correlated between the sexes.
      Males experienced significant negative selection, but only in populations with
      relatively limited water availability. Females experienced weakly positive or
      significant stabilizing selection on the same trait. Specific leaf area is
      genetically correlated with flower size and number, which are sexually dimorphic
      in this species. The extent of intralocus sexual conflict varied with the
      environment. Resolution of such conflict is likely to be confounded, given that
      specific leaf area is highly genetically integrated with other traits that are
      also divergent between the sexes.

PMID- 21726234
TI  - Maternal cytokine profiles during pregnancy - predictors for later allergy or
      just reading the tea leaves?

PMID- 21726236
TI  - Effects of enrofloxacin on cytochromes P4501A and P4503A in Carassius auratus
      gibelio (crucian carp).
AB  - Currently, although enrofloxacin (EF) as a widely used veterinary medicine has
      begun to apply to treating fish bacterial infections, the researches on the
      effects of EF on their main drug metabolic enzymes are limited. To investigate
      the effects of EF on fish cytochromes P450 (CYPs) 1A and 3A, the enzymatic
      activities and expressions (mRNA and protein) of crucian carp CYP1A and CYP3A
      after EF administration were examined. For CYP1A, in the in vivo experiments, EF
      exhibited potent inhibition on the CYP1A-related ethoxyresorufin-O-deethylase
      (EROD) activity, as well as CYP1A expressions at both protein and mRNA levels, at
      24 h after administration with different EF dosages (3, 10, 30, and 60 mg/kg);
      Furthermore, CYP1A enzymatic activity and expressions at both protein and mRNA
      levels decreased more with increasing EF dosages. Additionally, the in vitro
      experimental results showed that, after incubated with microsomes, EF did not
      change the EROD activity through interacting directly with CYP1A. For CYP3A, the
      in vitro and in vivo experimental results demonstrated that EF could inhibit the
      CYP3A-related erythromycin N-demethylase activity in a time- and dose-dependent
      manner, while it did not suppress CYP3A expressions at both protein and mRNA
      levels after administration with EF for a short period (no more than 24 h);
      however, after injection with EF at a high dose (10 mg/kg) for a long period, the
      CYP3A protein and mRNA reached their lowest levels at 96 and 48 h, respectively.
      These results indicate that EF can suppress CYP1A expressions in a dose-dependent
      manner, thereby inhibiting further its catalytic activity; meanwhile, both the
      interactions of EF with CYP3A and the expressions decrease (protein and mRNA)
      caused by EF contribute to the CYP3A inhibition.

PMID- 21726235
TI  - Primary brain tumours and specific serum immunoglobulin E: a case-control study
      nested in the European Prospective Investigation into Cancer and Nutrition
      cohort.
AB  - BACKGROUND: Case-control studies suggest that patients with allergic diseases
      have a lower risk of developing glioma but not meningioma or schwannoma. However,
      those data can be differentially biased. Prospective studies with objective
      measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood
      obtained before cancer diagnosis could help to clarify whether an aetiological
      association exists. METHODS: The present case-control study nested within the
      European Prospective Investigation into Cancer and Nutrition (EPIC) measured
      specific serum IgE as a biomarker for the most common inhalant allergens in 275
      glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the
      ImmunoCAP specific IgE test. Subjects with an IgE level >=0.35 kUA/l (kilo
      antibody units per litre) were classified as sensitized by allergens. Odds ratios
      (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional
      logistic regression models for each tumour subtype. The effect of dose-response
      relationship was assessed in five increasing IgE level categories to estimate P
      values for trend. RESULTS: The risk of glioma was inversely related to allergic
      sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR =
      0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the
      lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04).
      No association was seen for meningioma and schwannoma. CONCLUSION: The results,
      based on serum samples prospectively collected in a cohort study, provide some
      support for the hypothesis that individuals with allergic sensitization are at
      reduced risk of glioma and confirm results from previous case-control studies.

PMID- 21726237
TI  - A paralog of the MtN3/saliva family recessively confers race-specific resistance
      to Xanthomonas oryzae in rice.
AB  - Approximately one third of the identified 34 rice major disease resistance (R)
      genes conferring race-specific resistance to different strains of Xanthomonas
      oryzae pv. oryzae (Xoo), which causes rice bacterial blight disease, are
      recessive genes. However, only two of the recessive resistance genes have been
      characterized thus far. Here we report the characterization of another recessive
      resistance gene, xa25, for Xoo resistance. The xa25, localized in the centromeric
      region of chromosome 12, mediates race-specific resistance to Xoo strain PXO339
      at both seedling and adult stages by inhibiting Xoo growth. It encodes a protein
      of the MtN3/saliva family, which is prevalent in eukaryotes, including mammals.
      Transformation of the dominant Xa25 into a resistant rice line carrying the
      recessive xa25 abolished its resistance to PXO339. The encoding proteins of
      recessive xa25 and its dominant allele Xa25 have eight amino acid differences.
      The expression of dominant Xa25 but not recessive xa25 was rapidly induced by
      PXO339 but not other Xoo strain infections. The nature of xa25-encoding protein
      and its expression pattern in comparison with its susceptible allele in rice-Xoo
      interaction indicate that the mechanism of xa25-mediated resistance appears to be
      different from that conferred by most of the characterized R proteins.

PMID- 21726239
TI  - Photosynthetic photon flux density and phytochrome B interact to regulate
      branching in Arabidopsis.
AB  - Branching is regulated by environmental signals including phytochrome B (phyB)
      mediated responses to the ratio of red to far red light. While the mechanisms
      associated with phytochrome regulation of branching are beginning to be
      elucidated, there is little information regarding other light signals, including
      photosynthetic photon flux density (PPFD) and how it influences phytochrome
      mediated responses. This study shows that Arabidopsis (Arabidopsis thaliana)
      branching is modified by both varying PPFD and phyB status and that significant
      interactions occur between these variables. While phyB deficiency decreased
      branching when the PPFD was low, the effect was suppressed by high PPFD and some
      branching aspects were actually promoted. Photosynthesis measurements showed that
      PPFD may influence branching in phyB-deficient plants at least partially through
      a specific signalling pathway rather than directly through energy effects on the
      shoot. The expression of various genes in unelongated buds of phyB-deficient and
      phyB-sufficient plants grown under high and low PPFD demonstrated potential roles
      for several hormones, including auxin, cytokinins and ABA, and also showed
      imperfect correlation between expression of the branching regulators BRC1 and
      BRC2 and bud fate. These results may implicate additional undiscovered bud
      autonomous mechanisms and/or components contributing to bud outgrowth regulation
      by environmental signals.

PMID- 21726238
TI  - Safeners recruit multiple signalling pathways for the orchestrated induction of
      the cellular xenobiotic detoxification machinery in Arabidopsis.
AB  - Safeners enhance herbicide tolerance in crop plants but not in target weeds, thus
      improving herbicide selectivity. The safeners isoxadifen-ethyl and mefenpyr
      diethyl protect cereal crops from sulfonyl urea herbicides in postemergence
      application. The two safeners were shown here to induce the cellular xenobiotic
      detoxification machinery in Arabidopsis thaliana when applied to leaves in a way
      mimicking field application. Gene expression profiling revealed the induction of
      446 genes potentially involved in the detoxification process. Transgenic
      Arabidopsis plants expressing a reporter gene under control of a safener
      responsive maize promoter were used as a model system to study the safener
      signalling pathway. Reporter gene analysis in the tga2/3/5/6, sid2-2 and npr1
      mutants as compared with the wild-type background showed that safener
      inducibility required TGA transcription factors and salicylic acid (SA) in a NON
      EXPRESSOR of PR-1 (NPR1)-independent pathway converging on two as-1 promoter
      elements. For the majority of the safener-responsive Arabidopsis genes, a similar
      dependence on TGA transcription factors and/or SA was shown by gene expression
      profiling in wild-type plants as compared with the tga2/3/5/6 and sid2-2 mutants.
      Thirty-eight percent of the genes, however, were induced by safeners in a TGA/SA
      independent manner. These genes are likely to be controlled by WRKY transcription
      factors and cognate W-boxes in their promoters.

PMID- 21726240
TI  - Fluoride-containing nanoporous calcium-silicate MTA cements for endodontics and
      oral surgery: early fluorapatite formation in a phosphate-containing solution.
AB  - AIM: To test the chemical-physical properties and apatite-forming ability of
      experimental fluoride-doped calcium silicate cements designed to create novel
      bioactive materials for use in endodontics and oral surgery. METHODOLOGY: A
      thermally treated calcium silicate cement (wTC) containing CaCl(2) 5%wt was
      modified by adding NaF 1%wt (FTC) or 10%wt (F10TC). Cements were analysed by
      environmental scanning electron microscopy with energy-dispersive X-ray analysis,
      IR and micro-Raman spectroscopy in wet conditions immediately after preparation
      or after ageing in a phosphate-containing solution (Dulbecco's phosphate-buffered
      saline). Calcium and fluoride release and pH of the storage solution were
      measured. The results obtained were analysed statistically (Tukey's HSD test and
      two-way anova). RESULTS: The formation of calcium phosphate precipitates
      (spherulites) was observed on the surface of 24 h-aged cements and the formation
      of a thick bone-like B-type carbonated apatite layer (biocoating) on 28 day-aged
      cements. The rate of apatite formation was FTC>F10TC>wTC. Fluorapatite was
      detected on FTC and F10TC after 1 day of ageing, with a higher fluoride content
      on F10TC. All the cements released calcium ions. At 5 and 24 h, the wTC had the
      significantly highest calcium release (P<0.001) that decreased significantly over
      the storage time. At 3-28 days, FTC and F10TC had significantly higher calcium
      release than wTC (P<0.05). The F10TC had the significantly highest fluoride
      release at all times (P<0.01) that decreased significantly over storage time. No
      significant differences were observed between FTC and wTC. All the cements had a
      strong alkalinizing activity (OH(-) release) that remained after 28 days of
      storage. CONCLUSIONS: The addition of sodium fluoride accelerated apatite
      formation on calcium silicate cements. Fluoride-doped calcium silicate cements
      had higher bioactivity and earlier formation of fluorapatite. Sodium fluoride may
      be introduced in the formulation of mineral trioxide aggregate cements to enhance
      their biological behaviour. F-doped calcium silicate cements are promising bone
      cements for clinical endodontic use.

PMID- 21726241
TI  - Mechanical assistance by intra-aortic balloon pump counterpulsation during
      reperfusion increases coronary blood flow and mitigates the no-reflow phenomenon:
      an experimental study.
AB  - The effects of the intra-aortic balloon pump (IABP) counterpulsation on the
      extent of myocardial infarction (MI), the no-reflow phenomenon (NRP), and
      coronary blood flow (CBF) during reperfusion in an ischemia-reperfusion
      experimental model have not been clarified. Eleven pigs underwent occlusion of
      the mid left anterior descending coronary artery for 1 h, followed by reperfusion
      for 2 h. CBF, distal to the occlusion site, was measured. In six experiments,
      IABP support began 10 min before, and continued throughout reperfusion (IABP
      Group). Five pigs without IABP support served as controls. At the end of each
      experiment, the myocardial area at risk (MAR) of infarction and the extent of MI
      and NRP were measured. Hemodynamic measurements at baseline and during coronary
      occlusion were similar in both groups. During reperfusion, systolic aortic blood
      pressure was significantly lower in the IABP Group than in controls. In the IABP
      Group, CBF reached a peak at 5 min of reperfusion, gradually decreased, but
      remained higher than at baseline, and significantly higher than in controls
      throughout the 2 h of reperfusion. In controls, CBF increased significantly above
      baseline immediately after the onset of reperfusion, then returned to baseline
      within 90 min. The extent of NRP (37 +/- 25% vs. 68 +/- 17%, P = 0.047) and MI
      (39 +/- 23% vs. 67 +/- 13%, P = 0.036), both expressed as percentage of MAR, was
      significantly less in the IABP group than in controls. After prolonged myocardial
      ischemia, IABP assistance started just 10 min before and throughout reperfusion
      increased CBF and limited infarct size and extent of NRP.

PMID- 21726242
TI  - Hybrid model analysis of intra-aortic balloon pump performance as a function of
      ventricular and circulatory parameters.
AB  - We investigated the effects of the intra-aortic balloon pump (IABP) on
      endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and
      end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and
      ventricular energetics (external work [EW], pressure-volume area [PVA]) under
      different ventricular (E(max) and diastolic stiffness) and circulatory (arterial
      compliance) parameters. We derived a hybrid model from a computational model,
      which is based on merging computational and hydraulic submodels. The lumped
      parameter computational submodel consists of left and right hearts and systemic,
      pulmonary, and coronary circulations. The hydraulic submodel includes part of the
      systemic arterial circulation, essentially a silicone rubber tube representing
      the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and
      ventricular energetics (EW, PVA) were analyzed against the ranges of left
      ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness)
      (~0.08 and ~0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant)
      and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were
      performed comparing the selected variables before and during IABP assistance.
      Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance
      producing lower percentage changes in the selected variables. The changes in
      ventricular diastolic stiffness strongly influence both absolute value of EVR and
      its variations during IABP (71 and 65% for lower and higher arterial compliance,
      respectively). V(ed) and V(es) changes are rather small but higher for lower
      E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in
      higher TCBF and CO during IABP assistance (~35 and 10%, respectively). The use of
      this hybrid model allows for testing real devices in realistic, stable, and
      repeatable circulatory conditions. Specifically, the presented results show that
      IABP performance is dependent, at least in part, on left ventricular filling,
      ejection characteristics, and arterial compliance. It is possible in this way to
      simulate patient-specific conditions and predict the IABP performance at
      different values of the circulatory or ventricular parameters. Further work is
      required to study the conditions for heart recovery modeling, baroreceptor
      controls, and physiological feedbacks.

PMID- 21726243
TI  - Assessment of right pump outflow banding and speed changes on pulmonary
      hemodynamics during biventricular support with two rotary left ventricular assist
      devices.
AB  - The absence of an effective, easily implantable right ventricular assist device
      (RVAD) significantly diminishes long-term treatment options for patients with
      biventricular heart failure. The implantation of a second rotary left ventricular
      assist device (LVAD) for right heart support is therefore being considered;
      however, this approach exhibits technical challenges when adapting current
      devices to produce the lower pressures required of the pulmonary circulation.
      Hemodynamic adaptation may be achieved by either reducing the rotational speed of
      the right pump impeller or reducing the diameter of the right outflow cannula by
      the placement of a restricting band; however, the optimal value and influence of
      changes to each parameter are not well understood. Hemodynamics were therefore
      investigated using different banding diameters of the right outflow cannula (3
      6.5 mm) and pump speeds (500-4500 rpm), using two identical rotary blood pumps
      coupled to a pulsatile mock circulation loop. Reducing the speed of the right
      pump from 4900 rpm (for left ventricle support) to 3500 rpm, or banding the O10
      mm (area 78.5 mm2) right outflow graft to O5.4 mm (22.9 mm2) produced suitable
      hemodynamics. Pulmonary pressures were most sensitive to banding diameters,
      especially when RVAD flow exceeded LVAD flow. This occurred between O5.3 and O6.5
      mm (22.05-38.5 mm2) and speeds between 3200 and 4400 rpm, with the flow imbalance
      potentially leading to pulmonary congestion. Total flow was not affected by
      banding diameters and speeds below this range, and only increased slightly at
      higher values. Both right outflow banding or right pump speed reduction were
      found to be effective techniques to allow a rotary LVAD to be used directly for
      right heart support. However, the observed sensitivity to diameter and speed
      indicate that challenges may be presented when setting appropriate values for
      each patient, and control over these parameters is desirable.

PMID- 21726244
TI  - Planctomycetes diversity associated with macroalgae.
AB  - Planctomycetes associated with 12 macroalgae from the north coast of Portugal
      were isolated, using an improved method. A total of 138 isolates were found to
      comprise 10 operational taxonomic units (OTUs), with 65% of the strains being
      closely related to the species Rhodopirellula baltica. The other strains are
      probably new species or genera related to Rhodopirellula, Blastopirellula and
      Planctomyces. Some of the OTUs isolated are unique and have never been found
      before in previous studies. Catalyzed reporter deposition-FISH confirmed the
      presence of Planctomycetes on macroalgal surfaces. This study provides the first
      report of the cultured diversity of Planctomycetes on the epiphytic macroalgae
      community and presents clear evidence of their nutritional and intimate
      relationship.

PMID- 21726245
TI  - Functional adaptation of microbial communities from jet fuel-contaminated soil
      under bioremediation treatment: simulation of pollutant rebound.
AB  - To investigate the link between the functionality and the diversity of microbial
      communities under strong selective pressure from pollutants, two types of
      mesocosms that simulate natural attenuation and phytoremediation were generated
      using soil from a site highly contaminated with jet fuel and under air-sparging
      treatment. An increase in the petroleum hydrocarbon concentration from 4900 to
      18,500 mg kg(-1) dw soil simulated a pollutant rebound (postremediation pollutant
      reversal due to residual contamination). Analysis of soil bacterial communities
      by denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA gene
      fragments showed stronger changes and selection for a phylogenetically diverse
      microbial population in the mesocosms with pollutant-tolerant willow trees.
      Enumeration of the main subfamilies of catabolic genes characteristic to the site
      detected a rapid increase in the degradation potential of both systems. A marked
      increase in the abundance of genes encoding extradiol dioxygenases with a high
      affinity towards various catecholic substrates was found in the planted
      mesocosms. The observed adaptive response to the simulated pollutant rebound,
      characterized by increased catabolic gene abundance, but with different changes
      in the microbial structure, can be explained by functional redundancy in
      biodegrading microbial communities.

PMID- 21726246
TI  - Genetic diversity study of Chromobacterium violaceum isolated from Kolli Hills by
      amplified ribosomal DNA restriction analysis (ARDRA) and random amplified
      polymorphic DNA (RAPD).
AB  - AIM: Chromobacterium are saprophytes that cause highly fatal opportunistic
      infections. Identification and strain differentiation were performed to identify
      the strain variability among the environmental samples. We have evaluated the
      suitability of individual and combined methods to detect the strain variations of
      the samples collected in different seasons. METHODS AND RESULTS: Amplified
      ribosomal DNA restriction analysis (ARDRA) and random amplified polymorphic DNA
      (RAPD) profiles were obtained using four different restriction enzyme digestions
      (AluI, HaeIII, MspI and RsaI) and five random primers. A matrix of dice
      similarity coefficients was calculated and used to compare these restriction
      patterns. ARDRA showed rapid differentiation of strains based on 16S rDNA, but
      the combined RAPD and ARDRA gave a more reliable differentiation than when either
      of them was analysed individually. CONCLUSION: A high level of genetic diversity
      was observed, which indicates that the Kolli Hills' C. violaceum isolates would
      fall into at least three new clusters. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Results showed a noteworthy bacterial variation and genetic diversity of C.
      violaceum in the unexplored, virgin forest area.

PMID- 21726247
TI  - Physicochemical characterization and antioxidant activity of melanin from a novel
      strain of Aspergillus bridgeri ICTF-201.
AB  - AIMS: The aim of the study is to isolate and characterize a melanin pigment from
      a new strain of Aspergillus bridgeri isolated from rhizosphere soil of Eucalyptus
      tree and to investigate its antioxidant activity. METHODS AND RESULTS: The
      extracellular pigment was alkali soluble, acid-resistant and insoluble in organic
      solvents and water. The pigment was precipitated on treatment with FeCl(3),
      ammoniacal AgNO(3) and potassium ferricyanide and was bleached in the presence of
      oxidants and reductants. It was confirmed as melanin based on the Fourier
      transform infrared and electron paramagnetic resonance spectroscopy techniques
      apart from chemical analysis. Inhibition of melanin production by inhibitors like
      tricyclazole, 6-hydroxyflavanone, 4-hydroxy-7-methoxy-3-phenyl-coumarin, 7
      hydroxy-4-phenyl-coumarin and 7-hydroxy-3,4,8-trimethylcoumarin confirmed that
      melanin produced by A. bridgeri is synthesized by 1,8-dihydroxynaphthalene (DHN)
      melanin pathway. The melanin showed good free radical scavenging activity by DPPH
      method with an EC(50) of 54.12 MUg ml(-1). CONCLUSIONS: The results of the study
      indicate that the melanin produced by the newly isolated A. bridgeri strain is a
      member of DHN melanin family and exhibited significant free radical scavenging
      activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on
      characterization of DHN melanin produced by a novel strain of A. bridgeri and may
      find potential application as a natural antioxidant in the cosmetic and
      pharmaceutical industries.

PMID- 21726248
TI  - Increased health burden associated with Clostridium difficile diarrhoea in
      inflammatory bowel disease.

PMID- 21726250
TI  - Dried plums, constipation and the irritable bowel syndrome.

PMID- 21726252
TI  - IL28B rs12979860 C/T polymorphism in elderly chronic hepatitis C patients treated
      with pegylated-interferon and ribavirin.

PMID- 21726253
TI  - Every fourth patient with Crohn's disease has anti-TNF dependency.

PMID- 21726254
TI  - Incidence of acute severe infusion reactions to infliximab depends on definition
      used rather than assay.

PMID- 21726256
TI  - Use of tacrolimus in the treatment of autoimmune hepatitis: a single centre
      experience.

PMID- 21726258
TI  - The effects of a weakly acidic meal on gastric buffering and postprandial gastro
      oesophageal reflux.
AB  - BACKGROUND: Exclusion of the meal during ambulatory pH monitoring presumes that a
      meal completely buffers gastric acid and reflux of acidic food content cannot be
      distinguished from gastric acid. However, the ability of a meal to completely
      buffer gastric acid remains unclear. AIM: To determine the effect of a weakly
      acid meal on gastric buffering and oesophageal acid exposure. METHODS: Patients
      undergoing multichannel intraluminal impedance pH studies were given a standard
      weakly acidic meal (pH = 5.9). Gastric and oesophageal pH was measured during the
      meal and in 15 min intervals for 2 h postprandially. RESULTS: The study included
      30 patients, with pathological acid reflux detected in 18 patients. Complete
      gastric buffering occurred in seven patients (23%) and was lost in all patients
      within 75 min of the meal. Oesophageal acid was detected in 33% of patients
      within 30 min of the meal and 81% of patients during the 2 h postprandial period.
      Postprandial oesophageal acid exposure was greater in patients with pathological
      acid reflux (9 +/- 2.7% vs. 1.7 +/- 0.8% P = 0.05) with a trend towards more
      incomplete gastric acid buffering and significant differences when measuring weak
      acid reflux (pH 4-5). Acid reflux rarely occurred in the absence of gastric acid,
      with gastric acid present in 74 of 79 (94%) fifteen minute postprandial intervals
      with acid reflux. CONCLUSIONS: The ability of a meal to buffer gastric acid is
      poor. Early postprandial oesophageal acid reflux occurs in a substantial
      proportion of patients. Addition of a weakly acidic or pH neutral meal to
      ambulatory pH monitoring may unmask early postprandial acid reflux and provide
      data on gastric acid buffering.

PMID- 21726257
TI  - Randomised clinical trial: rabeprazole plus aspirin is not inferior to
      rabeprazole plus clopidogrel for the healing of aspirin-related peptic ulcer.
AB  - BACKGROUND: Clopidogrel does not inhibit prostaglandin synthesis. As a result,
      clopidogrel's incidence of peptic ulcer disease (PUD) and ulcer bleeding is lower
      than aspirin's. AIM: To compare the healing rate in aspirin-related dyspeptic
      ulcer patients who were given proton pump inhibitor (PPI) plus aspirin or PPI
      plus clopidogrel. METHODS: Patients with aspirin-related nonbleeding symptomatic
      ulcers were randomised to receive rabeprazole (20 mg/day) plus aspirin (100
      mg/day) or rabeprazole (20 mg/day) plus clopidogrel (75 mg/day) for 12 weeks. The
      primary endpoint was the successful treatment of PUD as characterised by
      intention-to-treat at the end of therapy. RESULTS: Two hundred and eighteen
      patients (109 in the aspirin group and 109 in the clopidogrel group) were
      enrolled. There were no statistical demographic differences between the group
      that received aspirin and the group that received clopidogrel. The PUD treatment
      success rate was also statistically equal between the clopidogrel and aspirin
      groups (86.2% vs. 90.0%, P = 0.531). Neither group experienced ulcer-related
      bleeding. Multivariate logistic regression analysis showed that large ulcer size
      (>10 mm) (OR: 6.29, 95% CI: 2.58-15.37) and past history of PUD (OR: 3.69, 95%
      CI: 1.24-10.97) were important predictors of unsuccessful therapy for aspirin
      related PUD. CONCLUSIONS: Rabeprazole plus aspirin is not inferior to rabeprazole
      plus clopidogrel in treating aspirin-related symptomatic PUD. Large ulcer size
      (>10 mm) and past history of PUD are important predictors of unsuccessful therapy
      (NCT 01037491).

PMID- 21726259
TI  - Use or refuse reproductive genetic technologies: which would a 'good parent' do?
AB  - A number of authors have objected to potential parents' use of reproductive
      genetic technologies on the grounds that the use of these technologies reflects a
      morally problematic attitude toward parenting. More specifically, proponents of
      this view have argued that such a choice is inconsistent with the unconditional
      acceptance that lies at the heart of praiseworthy parental attitudes. This paper
      offers a rebuttal of this view by arguing that it is possible for a parent to
      exhibit unconditional acceptance of the child herself without accepting each of
      that child's traits. If this is true, the use of reproductive genetic
      technologies does not inherently undermine appropriate parental attitudes.
      Further, by working to change some of a child's specific traits, a parent may
      instead exemplify an aspirational aspect of praiseworthy parenting and so
      demonstrate appropriate parental attitudes.

PMID- 21726260
TI  - No ethical bypass of moral status in stem cell research.
AB  - Recent advances in reprogramming technology do not bypass the ethical challenge
      of embryo sacrifice. Induced pluripotent stem cell (iPS) research has been and
      almost certainly will continue to be conducted within the context of embryo
      sacrifice. If human embryos have moral status as human beings, then participation
      in iPS research renders one morally complicit in their destruction; if human
      embryos have moral status as mere precursors of human beings, then advocacy of
      iPS research policy that is inhibited by embryo sacrifice concerns renders one
      morally complicit in avoidable harms to persons. Steps may be taken to address
      these complicity concerns, but in the final analysis there is no alternative to
      achieving clarity with respect to the moral status of the human embryo.

PMID- 21726261
TI  - Is payment a benefit?
AB  - What I call 'the standard view' claims that IRBs should not regard financial
      payment as a benefit to subjects for the purpose of risk/benefit assessment.
      Although the standard view is universally accepted, there is little defense of
      that view in the canonical documents of research ethics or the scholarly
      literature. This paper claims that insofar as IRBs should be concerned with the
      interests and autonomy of research subjects, they should reject the standard view
      and adopt 'the incorporation view.' The incorporation view is more consistent
      with the underlying soft-paternalist justification for risk-benefit assessment
      and demonstrates respect for the autonomy of prospective subjects. Adoption of
      the standard view precludes protocols that advance the interests of subjects,
      investigators, and society. After considering several objections to the argument,
      I consider several arguments for the standard view that do not appeal to the
      interests and autonomy of research subjects.

PMID- 21726262
TI  - Understanding doctors' ethical challenges as role virtue conflicts.
AB  - This paper argues that doctors' ethical challenges can be usefully conceptualised
      as role virtue conflicts. The hospital environment requires doctors to be
      simultaneously good doctors, good team members, good learners and good employees.
      I articulate a possible set of role virtues for each of these four roles, as a
      basis for a virtue ethics approach to analysing doctors' ethical challenges.
      Using one junior doctor's story, I argue that understanding doctors' ethical
      challenges as role virtue conflicts enables recognition of important moral
      considerations that are overlooked by other approaches to ethical analysis.

PMID- 21726263
TI  - Narratives of 'terminal sedation', and the importance of the intention-foresight
      distinction in palliative care practice.
AB  - The moral importance of the 'intention-foresight' distinction has long been a
      matter of philosophical controversy, particularly in the context of end-of-life
      care. Previous empirical research in Australia has suggested that general
      physicians and surgeons may use analgesic or sedative infusions with ambiguous
      intentions, their actions sometimes approximating 'slow euthanasia'. In this
      paper, we report findings from a qualitative study of 18 Australian palliative
      care medical specialists, using in-depth interviews to address the use of
      sedation at the end of life. The majority of subjects were agnostic or atheistic.
      In contrast to their colleagues in acute medical practice, these Australian
      palliative care specialists were almost unanimously committed to distinguishing
      their actions from euthanasia. This commitment appeared to arise principally from
      the need to maintain a clear professional role, and not obviously from an
      ideological opposition to euthanasia. While some respondents acknowledged that
      there are difficult cases that require considered reflection upon one's
      intention, and where there may be some 'mental gymnastics,' the nearly unanimous
      view was that it is important, even in these difficult cases, to cultivate an
      intention that focuses exclusively on the relief of symptoms. We present four
      narratives of 'terminal' sedation--cases where sedation was administered in
      significant doses just before death, and may well have hastened death.
      Considerable ambiguities of intention were evident in some instances, but the
      discussion around these clearly exceptional cases illustrates the importance of
      intention to palliative care specialists in maintaining their professional roles.

PMID- 21726264
TI  - Uncertain translation, uncertain benefit and uncertain risk: ethical challenges
      facing first-in-human trials of induced pluripotent stem (ips) cells.
AB  - The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a
      major breakthrough in stem cell research. Since then, progress in iPS cell
      technology has paved the way towards clinical application, particularly cell
      replacement therapy, which has refueled debate on the ethics of stem cell
      research. However, much of the discourse has focused on questions of moral status
      and potentiality, overlooking the ethical issues which are introduced by the
      clinical testing of iPS cell replacement therapy. First-in-human trials, in
      particular, raise a number of ethical concerns including informed consent,
      subject recruitment and harm minimisation as well as the inherent uncertainty and
      risks which are involved in testing medical procedures on humans for the first
      time. These issues, while a feature of any human research, become more complex in
      the case of iPS cell therapy, given the seriousness of the potential risks, the
      unreliability of available animal models, the vulnerability of the target patient
      group, and the high stakes of such an intensely public area of science. Our paper
      will present a detailed case study of iPS cell replacement therapy for
      Parkinson's disease to highlight these broader ethical and epistemological
      concerns. If we accept that iPS cell technology is fraught with challenges which
      go far beyond merely refuting the potentiality of the stem cell line, we conclude
      that iPS cell research should not replace, but proceed alongside embryonic and
      adult somatic stem cell research to promote cross-fertilisation of knowledge and
      better clinical outcomes.

PMID- 21726265
TI  - The ethics of uterus transplantation.
AB  - Human uterus transplantation (UTx) is currently under investigation as a
      treatment for uterine infertility. Without a uterus transplant, the options
      available to women with uterine infertility are adoption or surrogacy; only the
      latter has the potential for a genetically related child. UTx will offer
      recipients the chance of having their own pregnancy. This procedure occurs at the
      intersection of two ethically contentious areas: assisted reproductive
      technologies (ART) and organ transplantation. In relation to organ
      transplantation, UTx lies with composite tissue transplants such as face and limb
      grafts, and shares some of the ethical concerns raised by these non-life saving
      procedures. In relation to ART, UTx represents one more avenue by which a woman
      may seek to meet her reproductive goals, and as with other ART procedures, raises
      questions about the limits of reproductive autonomy. This paper explores the
      ethical issues raised by UTx with a focus on the potential gap between women's
      desires and aspirations about pregnancy and the likely functional outcomes of
      successful UTx.

PMID- 21726266
TI  - Increased prevalence of impaired fasting glucose in MEN1 gene mutation carriers.
AB  - OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome
      characterized by parathyroid, gastroenteropancreatic, pituitary and adrenal
      tumours. Cardiovascular disease has been identified as an important cause of
      death in MEN1 patients. Menin, the product of the MEN1 gene, is a co-activator
      for peroxisome proliferator-activated receptor-gamma and the vitamin D receptor,
      which are involved in glucose metabolism. We aimed to compare insulin sensitivity
      and prevalence of impaired fasting glucose and diabetes mellitus between MEN1
      patients and controls. DESIGN: Cross-sectional study. PATIENTS: Sixty-three MEN1
      gene mutation carriers (44% men, mean age 41 years) from 22 kindreds and 126
      unrelated controls matched for gender, age and BMI. MEASUREMENTS: Fasting glucose
      levels were categorized and compared using WHO criteria. Homeostasis model
      assessment (HOMA) was used as a measure of insulin resistance. RESULTS:
      Homeostasis model assessment was significantly increased in MEN1 patients
      compared with controls (3.0 +/- 2.0 vs 2.0 +/- 1.0, P < 0.05). In MEN1 patients,
      HOMA was associated with BMI, but not with age, calcium and gastrin levels. Using
      logistic regression analysis, the presence of hyperparathyroidism, pancreatic
      lesions and various other manifestations was not associated with HOMA. Impaired
      fasting glucose was more prevalent in MEN1 compared with controls (17%vs 6%, P <
      0.05). Three MEN1 patients (5%) compared with four controls (3%) were diabetic
      (not significant). CONCLUSIONS: Multiple endocrine neoplasia type 1 patients had
      decreased insulin sensitivity and higher prevalence of impaired fasting glucose
      compared with controls, which was unrelated to MEN1 manifestations. Impaired
      glucose metabolism may result in increased risk of cardiovascular disease in MEN1
      patients.

PMID- 21726267
TI  - A meta-analysis of the association of adiponectin gene polymorphisms with
      coronary heart disease in Chinese Han population.
AB  - OBJECTIVE:   Variants of adiponectin gene have been reported to be associated
      with coronary heart disease (CHD), but the available data on this relationship
      are inconsistent. A meta-analysis was performed to quantitatively analyse the
      association of adiponectin gene polymorphisms with coronary artery disease using
      previous case-control studies in Chinese Han populations. METHODS:   Several
      electronic databases were searched for relevant articles up to January 2011.
      After data collection and gene loci selection, a meta-analysis was performed to
      assess heterogeneity, combine results and evaluate variations. Publication bias
      was examined by the Egger's linear regression test. Hardy-Weinberg equilibrium
      (HWE) test and by omitting one study at a time was employed for the sensitivity
      analysis. RESULTS:   Eleven studies covering 4303 subjects focusing on two
      polymorphisms [+45T->G (rs2241766) and +276G->T (rs1501299)] in the adiponectin
      gene and risk of CHD were included in the meta-analysis. Combined analyses of
      studies of the SNP+45 showed no significant overall association with CHD,
      yielding ORs of 1.03 (0.80, 1.34) and 1.32 (0.86, 2.03) under a dominant and
      recessive model, respectively, with strong evidence of heterogeneity. Similar
      results were also obtained in other genetic models. Concerning SNP+276, a
      significantly decreased CHD risk was observed under a dominant model, a
      codominant model and a allele contrast model, with an odds ratio of 0.67 (0.54,
      0.83), 0.77 (0.62, 0.94) and 0.69 (0.55, 0.86), respectively. Sensitivity
      analysis confirmed the reliability and stability of this meta-analysis.
      CONCLUSIONS:   The accumulated evidence suggested that the adiponectin gene
      polymorphism, SNP+45, is not associated with CHD, but the SNP+276T allele might
      be associated with decreased risk of CHD in the Chinese Han population. More well
      designed large studies are required for the validation of this association.

PMID- 21726268
TI  - Dentists' use of caries risk assessment and individualized caries prevention for
      their adult patients: findings from The Dental Practice-Based Research Network.
AB  - OBJECTIVES: Few studies have examined dentists' subjective ratings of importance
      of caries risk factors or tested whether dentists use this information in
      treatment planning. This study tested several hypotheses related to caries risk
      assessment (CRA) and individualized caries prevention (ICP). METHODS: Data were
      collected as part of a questionnaire entitled 'Assessment of Caries Diagnosis and
      Caries Treatment', completed by 547 practitioners who belong to The Dental
      Practice-Based Research Network (DPBRN), a consortium of participating practices
      and dental organizations. RESULTS: Sixty-nine percent of DPBRN dentists perform
      CRA on their patients. Recently graduated dentists, dentists with busier
      practices, and those who believe a dentist can predict future caries were the
      most likely to use CRA. The association between CRA and individualized prevention
      was weaker than expected (r = 0.21). Dentists who perform CRA provide ICP to 57%
      of their patients, compared with 42% for dentists who do not perform CRA. Based
      on their responses to radiographic and clinical scenarios in the questionnaire,
      dentists who use CRA appear to use this information in restorative decisions.
      CONCLUSION: A substantial percentage of DPBRN dentists do not perform CRA, and
      there is not a strong linkage between its use and use of individualized
      preventive regimens for adult patients. More progress in the implementation of
      current scientific evidence in this area is warranted.

PMID- 21726269
TI  - Low inhibin B levels alone are not a reliable marker of dysfunctional
      spermatogenesis in childhood cancer survivors.
AB  - Hormone and semen analyses were carried out to examine the diagnostic value of
      hormones and hormone combinations as markers of spermatogenesis in male patients
      who had received oncological treatment in childhood. Hormone analyses from 73
      participants and spermiograms from 42 participants were evaluated. Spearman's
      correlation coefficients and measures of diagnostic accuracy were calculated for
      the hormone and semen analysis values. Inhibin B levels of <80 ml/ml, follicle
      stimulating hormone (FSH) levels of >10 IU l(-1) and a combination of the two
      parameters showed positive predictive values for azoospermia of 0.423, 0.6154 and
      0.6667 respectively. While 32% of the 73 participants showed a combination of
      abnormal inhibin B and FSH values, which strongly indicates impaired
      spermatogenesis, 31% of the 42 spermiogram results revealed azoospermia. The
      hormone and semen analyses showed that approximately one-third of the
      participants had fertility impairment. Inhibin B alone thus does not reflect
      spermatogenesis as well as inhibin B in combination with FSH in patients who have
      undergone cancer treatment in childhood. Both parameters should therefore be
      evaluated in paediatric cancer follow-up programmes to allow better
      identification of treatment regimens that cause persistent azoospermia in male
      childhood cancer survivors.

PMID- 21726270
TI  - Hirano body-rich subtypes of Creutzfeldt-Jakob disease.
AB  - BACKGROUND: In definite Creutzfeldt-Jakob disease (CJD), morphological and
      immunohistochemical patterns are useful to identify molecular subtypes. Severe
      cerebellar pathology and hippocampal involvement helps to identify VV subtypes.
      The rare VV1 variant (<1%), more frequent in young individuals, is additionally
      characterized by the presence of ballooned neurones in affected areas. In 1985,
      Cartier et al. described a family cluster of three individuals with an ataxic CJD
      form, showing, in addition to severe cerebellar and hippocampal involvement, the
      presence of frequent Hirano bodies (HB) in CA1 pyramidal neurones. HB are
      frequently found in aged individuals with Alzheimer pathology although they are
      not a specific finding. AIMS AND METHODS: In this study, we evaluated the
      presence of HB in hippocampi of 54 genetically and molecularly characterized CJD
      cases, aiming to elucidate whether additional morphological features could be
      helpful to point to molecular subtypes. RESULTS: We identified nine cases (four
      VV1, one out of three MV2K, three out of six MV2K+2C and one MV carrying a 96
      base pair insertion) with abundant, partly bizarre and clustered HB in CA1
      sector, not observed in other subtypes. The presence of HB was independent of
      hippocampal involvement by the disease itself. CONCLUSIONS: Clusters of abundant
      HB might be found in rare CJD subtypes such as VV1, MV2K/MV2K+2C and some genetic
      cases. In addition to histopathological and PrP immunohistochemical deposition
      patterns, their presence might be a useful additional morphologic feature that
      could point to the molecular subtype, especially when genetic and/or Western blot
      analyses are not available.

PMID- 21726271
TI  - Frontotemporal lobar degeneration in a very young patient is associated with
      fused in sarcoma (FUS) pathological changes.

PMID- 21726272
TI  - Eating difficulties among patients 3 months after stroke in relation to the acute
      phase.
AB  - AIM: This paper is a report of a study comparing eating difficulties among
      patients 3 months after stroke in relation to the acute phase. BACKGROUND: There
      is limited knowledge of patients with eating problems early after stroke, hence
      the progress of eating abilities needs to be further explored. METHOD: From March
      2007 to June 2008 36 stroke patients with 2-7 eating difficulties or problems
      with reduced alertness or swallowing in the acute phase were included. Eating
      difficulties were detected using a structured protocol of observation of meals.
      In addition, stroke severity (National Institute of Health Stroke Scale),
      functional status (Barthel Index), unilateral neglect (Line Bisection test and
      Letter Cancellation test), psychological well-being (The Well-being Questionnaire
      12), nutritional status (Mini Nutritional Assessment) and oral status (Revised
      Oral Assessment Guide) were assessed. RESULTS: There were 36 participants (58%
      female) with a median age of 74.5 years. The proportion of eating difficulties
      decreased significantly from the acute phase to the 3-month follow-up in 'sitting
      position', 'managing food on the plate' and 'manipulating food in the mouth' and
      increased regarding inadequate food consumption. Improvements were shown at 3
      months in stroke severity, functional status, nutritional status and neglect.
      Oral status and psychological well-being remained unchanged. CONCLUSION: The
      majority of eating problems persisted 3 months after stroke despite a marked
      improvement in most of the physical functions. The unchanged psychological well
      being and sustained problems with food consumption indicate that factors other
      than physical function should be taken into account regarding eating difficulties
      poststroke.

PMID- 21726273
TI  - Nocturnal masseter electromyographic activity of complete denture wearers.
AB  - OBJECTIVE: Collection of normative data on activity patterns of the masseter
      during sleep in elderly denture wearers by portable electromyography (EMG)
      recorders. BACKGROUND: Complete denture wearers might suffer from orofacial pain
      caused by myoarthropathies of the masticatory system. Indeed, denture instability
      may precipitate parafunctional habits and consequently muscle soreness and/or
      temporomandibular pain. MATERIALS AND METHODS: We collected normative masseter
      EMG data during sleep in 15 complete denture wearers (five women, 10 men, 56-88
      years) by portable recorders in their natural environment. Activity periods (AP)
      were signal portions including subthreshold intervals <=5 s. Signal amplitude was
      expressed in per cent of maximum voluntary contraction (%MVC). For this reason,
      maximum bite force was assessed. Twenty age-matched dentate controls were also
      recorded for the maximum bite force. RESULTS: We found 157.2 +/- 86.5 AP per
      night, i.e. 24.0 +/- 12.2 AP/h. Mean amplitude was 15.1 +/- 4.3%MVC. AP lasted
      6.8 +/- 4.1 s, and their time integral was 126.3 +/- 112.5%MVC*s. Maximum bite
      force was 116.8 +/- 69.6 N in the edentulous, significantly lower than in
      controls (344.8 +/- 150.4 N). CONCLUSIONS: Healthy complete denture wearers
      showed intermittent periods of nocturnal masseter activity of very low intensity
      and short duration.

PMID- 21726274
TI  - Oral and general health status in patients treated in a dental consultation
      clinic of a geriatric ward in Bern, Switzerland.
AB  - INTRODUCTION: This audit reports on the oral and general health of patients who
      were treated in a dental consultation clinic of a geriatric hospital. MATERIAL
      AND METHODS: Dental and medical records were obtained from 112 female and 80 male
      patients (mean age, 83.7 +/- 8.2 years) who attended a dental consultation. Data
      analysis included the general health [American Society of Anesthesiologists (ASA)
      classification, number of diagnoses, cognitive function] and dental state in the
      age strata 60-69, 70-79, 80-89 and 90-99 years. RESULTS: Seventy-four per cent of
      patients were aged over 80 years. The prevalence of ASA-P4 and P3 varied between
      age groups. Most patients (>86%) had more than three chronic diseases. Cognitive
      impairment was present in almost half of both older age cohorts (43 and 50%).
      Half of the patients (52%) were edentulous. In dentate patients, the average
      number of teeth was 12 +/- 6 and differed in the maxilla significantly between
      age groups (p = 0.005). There was no significant association between dental
      state, ASA classification and systemic conditions. CONCLUSIONS: The profile of
      this cohort reflects a poor oral and general health status. The results underline
      the importance of an interdisciplinary consultation in a geriatric ward where
      oral health care is an integral part.

PMID- 21726275
TI  - Trigeminal neuralgia: a retrospective study of 188 Thai cases.
AB  - OBJECTIVE: To describe the clinical characteristics and treatment of trigeminal
      neuralgia (TN) in a group of Thai patients. MATERIALS AND METHODS: Records of 188
      patients with TN were reviewed retrospectively for patient demographics, the
      characteristics of the pain and treatment modalities. RESULTS: Of the 188
      patients, 37.2% were men and 62.8% were women. The peak incidence (46.8%) was in
      the age range of 50-69 years. Pain occurred on the right side of the face more
      often than on the left (1.8:1). The mandibular division of the trigeminal nerve
      was the most frequently affected (30.3%), followed by the combined maxillary and
      mandibular divisions (29.3%) and the maxillary division alone (25%). The majority
      described their attack as a sharp pain (77.6%), and the most common primary
      locations were at previous extraction sites (40.5%). The most common triggers
      were chewing (61.2%) and speaking (47.3%). Carbamazepine was the most common
      prescribed drug (76.1%) for the initial treatment. Combination drug therapy was
      introduced when the monotherapy failed to control the pain. Surgical intervention
      was the alternative choice of treatment in refractory cases. CONCLUSION: TN
      affected women more than men, and this disorder occurred most frequently in
      patients aged 50 years and older. The mandibular division of the trigeminal nerve
      was most commonly involved.

PMID- 21726276
TI  - The effect of attachment type and implant number on satisfaction and quality of
      life of mandibular implant-retained overdenture wearers.
AB  - OBJECTIVE: The aim of this study was to compare the quality of life and patient
      satisfaction outcomes of two attachment systems in mandibular overdentures with
      different numbers of supporting implants. MATERIALS AND METHODS: Sixty-two
      edentulous patients with either splinted or single attachments in mandibular
      implant overdentures with different numbers of supporting interforaminal implants
      were investigated for patient satisfaction and quality of life in this
      retrospective study. Comparisons between groups were perceived by the Mann
      Whitney U test. Relations among the parameters were investigated by Spearman's
      rho correlation analysis. The results were evaluated statistically at a
      significance level of p < 0.05. RESULTS: No statistically significant association
      is found between visual analogue scales scores and attachment type as well as
      implant number (p > 0.05), whereas Oral Health Impact Profile (OHIP)-14 total
      scores for patients with 4-implant-supported bars were significantly lower than
      all the other attachment types (p < 0.05). Additionally, a negative (rate =
      32.2%), statistically significant association between period of edentulism and
      total OHIP-14 scores was detected (p < 0.05). CONCLUSIONS: A mandibular implant
      retained overdenture supported with four implants and bar attachments shows the
      highest 'quality of life' score and patient satisfaction is not influenced by the
      number of implants or attachment type.

PMID- 21726277
TI  - Presentation and clinical course of Wolfram (DIDMOAD) syndrome from North India.
AB  - AIMS: Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited
      neurodegenerative disorder, first evident in childhood as an association of
      juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes
      insipidus and deafness. The aim of the study was to examine the clinical profile
      of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north
      India. METHODS: Clinical presentation of juvenile-onset diabetes mellitus
      fulfilling the diagnosis of Wolfram syndrome was studied using a prepared
      standardized form. RESULTS: Subjects with juvenile-onset non-autoimmune diabetes
      mellitus attending the diabetic clinic at a tertiary care centre in north India
      were followed for 10 years and a diagnosis of fully developed Wolfram syndrome
      was confirmed in seven individuals. The series consisted of five male and two
      female patients with a mean age of 17.5 +/-7.34 years. Two subjects had
      consanguinity and none had any other family member affected. Optic atrophy was
      present in all, sensorineural hearing loss in 4/7, central diabetes insipidus in
      4/7 and nephrogenic diabetes insipidus in 2/7 subjects. The new associations
      found were: spastic myoclonus, short stature with pancreatic malabsorption,
      nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis
      with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene
      in all the cases studied. CONCLUSIONS: The present clinical series of Wolfram
      syndrome reveals a varied clinical presentation of the syndrome and some new
      associations.

PMID- 21726278
TI  - Cut-off values of fasting and post-load plasma glucose and HbA1c for predicting
      Type 2 diabetes in community-dwelling Japanese subjects: the Hisayama Study.
AB  - AIMS: We examined the optimal cut-off values of fasting plasma glucose, 2-h post
      load glucose and HbA(1c) for predicting Type 2 diabetes in community-dwelling
      Japanese subjects. METHODS: A total of 1982 subjects without diabetes aged 40-79
      years who underwent a 75-g oral glucose tolerance test were followed
      prospectively for 14 years by annual health examination. RESULTS: During the
      follow-up, 295 subjects developed Type 2 diabetes. Compared with the first
      decile, the crude hazard ratio for incident Type 2 diabetes was significantly
      higher in the fifth fasting plasma glucose decile [5.4-5.4 mmol/l (97-98 mg/dl)]
      or higher, in the seventh 2-h post-load glucose decile [6.9-7.2 mmol/l (124-131
      mg/dl)] or higher, and in the fifth HbA(1c) decile [34-36 mmol/mol (5.3-5.4%)] or
      higher. These associations remained substantially unchanged even after adjustment
      for confounding factors. The receiver operating characteristic curve analysis
      showed that the optimal cut-off values for predicting Type 2 diabetes were 5.6
      mmol/l (101 mg/dl) for fasting plasma glucose, 6.9 mmol/l (124 mg/dl) for 2-h
      post-load glucose and 37 mmol/mol (5.5%) for HbA(1c). In a stratified analysis,
      the cut-off values were approximately 5.6 mmol/l (101 mg/dl) for fasting plasma
      glucose and 37 mmol/mol (5.5%) for HbA(1c), and these values were unchanged over
      BMI quartile levels, whereas the 2-h post-load glucose cut-off values declined
      with decreasing BMI levels. CONCLUSIONS: Our findings suggest that the cut-off
      value for predicting Type 2 diabetes in the Japanese population is 5.6 mmol/l
      (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), while
      the 2-h post-load glucose cut-off value is lower than the diagnostic criterion
      for impaired glucose tolerance.

PMID- 21726279
TI  - Association between vitamin D and diabetic neuropathy in a nationally
      representative sample: results from 2001-2004 NHANES.
AB  - AIMS: To evaluate the association between vitamin D insufficiency and peripheral
      neuropathy in a nationally representative sample of adults with diagnosed
      diabetes. METHODS: Vitamin D concentrations, medical examination variables and
      questionnaire results from the 2001-2004 National Health and Nutrition
      Examination Survey were analysed for adults >= 40 years old with diagnosed
      diabetes (unweighted n = 591, weighted n = 8.82 million). Neuropathy was defined
      as self report of peripheral neuropathy symptoms of painful sensation, tingling,
      numbness or loss of feeling in hands or feet. Additionally, Semmes-Weinstein
      monofilament test results were used as an indicator of neuropathy. Insufficient
      vitamin D was characterized as < 30 ng/ml. RESULTS: In the weighted population,
      81% of adults with diabetes had vitamin D insufficiency. Vitamin D insufficiency
      was more common among Hispanics (92%) and non-Hispanic black people (98%) than
      among non-Hispanic white people (76%). Within the 3 months preceding the
      questionnaire, 50% reported experiencing pain or numbness (paresthesia) in their
      hands or feet; 37% reported pain or tingling in hands or feet; and 38% reported
      numbness or loss of feeling in hands or feet. Eight per cent had 4-6 insensate
      areas on their feet as determined by the Semmes-Weinstein monofilament test.
      Logistic regressions demonstrate vitamin D insufficiency is associated with the
      adjusted composite paresthesia measure (odds ratio 2.12; 95% CI 1.17-3.85) and
      the adjusted numbness measure (odds ratio 2.04; 95% CI 1.18-3.52). CONCLUSIONS:
      Vitamin D insufficiency is associated with self-reported peripheral neuropathy
      symptoms even after adjusting for demographic factors, obesity, co-morbidities,
      use of medications for neuropathy and diabetes duration and control.

PMID- 21726280
TI  - Effect of exercise intensity on albuminuria in adolescents with Type 1 diabetes
      mellitus.
AB  - AIMS: Exercise may be useful to detect patients with diabetes prone to develop
      persistent microalbuminuria. We studied the relationship between exercise
      intensity, measured as maximal oxygen consumption (VO(2)max), and
      microalbuminuria in patients with Type 1 diabetes mellitus patients. METHODS: We
      studied 10 patients, age range 10-18 years, with Type 1 diabetes who were
      normotensive and normoalbuminuric, with less than 10 years since diagnosis.
      Patients had normal renal function, without infections or clinical evidence of
      complications. Metabolic control was intensively adjusted in all patients. They
      underwent three consecutive physical exercise tests, reaching 100, 80 and 60% of
      the maximal cardiac frequency response. RESULTS: Eight patients had adequate to
      regular metabolic control. All patients had lower than predicted VO(2)max values.
      At 60%, only three patients showed microalbuminuria in excess of 20 MUg/min, two
      of them had inadequate metabolic control. Post-exercise microalbuminuria exceeded
      normal values in nine, seven and three patients when submitted to 100, 80 and 60%
      of exercise intensity, respectively. CONCLUSIONS: Microalbuminuria increased with
      exercise intensity. Sex, body composition and VO(2)max were the main factors
      associated with microalbuminuria. The prognostic significance of albuminuria
      induced by intense exercise in these subjects with Type 1 diabetes is not yet
      known.

PMID- 21726281
TI  - Serum adiponectin, bone mineral density and bone turnover markers in post
      menopausal women with newly diagnosed Type 2 diabetes: a 12-month follow-up.
AB  - OBJECTIVE: During a period of 12 months, we evaluated the longitudinal impact of
      metabolic control of diabetes on selected bone turnover markers, bone mineral
      density and serum adiponectin concentrations in post-menopausal women with newly
      diagnosed Type 2 diabetes. METHODS: Serum total adiponectin, bone alkaline
      phosphatase, HbA(1c), urinary deoxypyridinoline excretion, bone mineral density
      of the total body, lumbar spine and total hip were measured in 57 women aged 50
      78 years with newly diagnosed Type 2 diabetes. RESULTS: At baseline, women had
      normal bone-specific alkaline phosphatase, deoxypyridinoline and bone mineral
      density, as evaluated by t- and z-scores. After 12 months of treatment, a
      significant decrease in body weight, waist circumference and HbA(1c) was
      observed. Bone mineral density of the total body, lumbar spine and total hip
      decreased by 0.4, 0.2 and 1.0% (P = 0.018) per year, respectively. Adiponectin
      was inversely correlated with bone mineral density at three sites (R = -0.28, 
      0.24 and -0.19, respectively). There was a transient increase (P < 0.05) in serum
      adiponectin within the first 6 months, followed by a slow decrease toward the
      baseline value during the next 6 months. An improvement in diabetes control had
      no impact on bone turnover marker levels, which did not change significantly
      during the entire study period. CONCLUSIONS: Bone turnover markers, bone mineral
      density and the rate of bone loss are within normal ranges in post-menopausal
      women with newly diagnosed Type 2 diabetes. Bone mineral density of the total
      body, lumbar spine and total hip is inversely correlated with total adiponectin.

PMID- 21726282
TI  - Maternal and neonatal factors associated with poor early weight gain and later
      retinopathy of prematurity.
AB  - AIM: To identify factors associated with poor early weight gain as reflected in
      an alarm system, WINROP, and risk of later proliferative retinopathy of
      prematurity (ROP) in infants with gestational age (GA) < 28 weeks. METHODS:
      Infants with a WINROP alarm and proliferative ROP, the 'alarm group' (n = 23),
      were matched to GA and gender to a 'no alarm group' (n = 23) with no WINROP alarm
      and no or mild ROP. Retrospectively maternal variables, birth characteristics and
      neonatal factors, during the first three postnatal weeks, were compared. RESULTS:
      The 'alarm group' had lower birth weight (BW) and BW standard deviation score,
      longer stay in ventilator, more insulin and corticosteroid treatments, and lower
      white blood cell count. In a logistic regression model, BW standard deviation
      score, insulin, low white blood cell count, absence of both elevated C-reactive
      protein and premature rupture of membranes were associated with proliferative ROP
      and WINROP alarm (p = 0.000, r(2) = 0.704). CONCLUSIONS: This study shows that
      prenatal factors resulting in low BW have persisting effects on early postnatal
      growth, metabolism and inflammatory response. Future prospective studies will
      focus on the link between these factors and pathological retinal vessel
      development in the early postnatal period to find possible preventive strategies.

PMID- 21726283
TI  - Impact of infancy duration on adult size in 22 subsistence-based societies.
AB  - AIM: Humans evolved to withstand harsh environments by adaptively decreasing
      their body size. Thus, adaptation to a hostile environment defers the infancy
      childhood transition age (ICT), culminating in short stature. In natural
      fertility human societies, this transition is associated with weaning from
      breastfeeding and the mother's new pregnancy. We therefore used the interbirth
      interval (IBI) as a surrogate for the ICT. METHODS: We hypothesized that long IBI
      will be associated with smaller body size. The sample used is 22 subsistence
      based societies of foragers, horticulturalists and pastorals from Africa, South
      America, Australia and Southeast Asia. RESULTS: The IBI correlated negatively
      with the average adult bodyweight but not height. After correction for 'pubertal
      spurt takeoff' and 'weight at age 5', the IBI explains 81% of 'average adult
      weight' variability. CONCLUSIONS: This inter-population study confirms that body
      weight is adaptively smaller in hostile environments and suggests that the
      selected trait for this adaptation is the ICT age.

PMID- 21726284
TI  - Reliability of energy cost calculations in children with cerebral palsy, cystic
      fibrosis and healthy controls.
AB  - AIM: To study test-retest reliability of physiological cost index (PCI) and total
      cost index (TCI) in three groups of children. TCI modified PCI by excluding rest
      heart rate in calculation. METHODS: Energy cost was evaluated from two
      consecutive walking tests, and results were compared between methods, tests and
      groups. Thirty-nine children, eight with cerebral palsy, 11 with cystic fibrosis
      and 20 healthy controls, aged 5-16 years participated in the study conducted at
      the Clinical Nutrition and Metabolism laboratory, University Hospital, Uppsala,
      Sweden. Heart rate was recorded during sitting and walking at self-selected
      speed. PCI and TCI were calculated using both non-steady-state and steady-state
      work heart rates. Test-retest reliability was analysed by mean of differences,
      pooled SD, coefficient of variation (CV%) and correlation coefficients. RESULTS:
      Reliability was high for PCI and TCI. TCI showed consistently lower variation
      between tests than PCI for all groups. In the group with cerebral palsy, using
      non-steady-state showed highest reliability. CONCLUSION: Both PCI and TCI were
      reliable methods when calculating energy cost in children with cerebral palsy,
      cystic fibrosis and controls. TCI seemed to be a suitable alternative in the
      evaluation of gait efficiency in children.

PMID- 21726285
TI  - Does routine analysis of subgingival microbiota in periodontitis contribute to
      patient benefit?
AB  - In clinical periodontology it is common practice to sample subgingival plaque
      from periodontitis patients and to search for the presence of alleged periodontal
      pathogens using routine laboratory techniques such as culture, DNA-DNA
      hybridization or real-time PCR. Usually, special attention is given to the
      recognition of 'red complex' microorganisms and to Aggregatibacter
      actinomycetemcomitans. Recently, molecular open-ended techniques have been
      introduced which are distinct from the more 'classical' approaches in that they
      do not preselect for certain species. In this study, we investigated to what
      extent the outcome of these techniques has changed our insight into the
      composition of the subgingival microbiota and whether this has consequences on
      clinical decision making. The open-ended approaches showed that the composition
      of subgingival plaque is much more complex than previously thought. Next to the
      'classical' putative periodontal pathogens, several non-culturable and fastidious
      species are now recognized as being associated with periodontitis, thus enlarging
      the group of suspected periodontal pathogens. We conclude that routine analyses
      of subgingival plaque in the clinic are not necessarily of benefit to the
      patient.

PMID- 21726286
TI  - Morphogenesis and bone integration of the mouse mandibular third molar.
AB  - The mouse third molar (M3) develops postnatally and is thus a unique model for
      studying the integration of a non-mineralized tooth with mineralized bone. This
      study assessed the morphogenesis of the mouse M3, related to the alveolar bone,
      comparing M3 development with that of the first molar (M1), the most common model
      in odontogenesis. The mandibular M3 was evaluated from initiation to eruption by
      morphology and by assessing patterns of proliferation, apoptosis, osteoclast
      distribution, and gene expression. Three-dimensional reconstruction and explant
      cultures were also used. Initiation of M3 occurred perinatally, as an extension
      of the second molar (M2) which grew into a region of soft mesenchymal tissue
      above the M2, still far away from the alveolar bone. The bone-free M3 bud
      gradually became encapsulated by bone at the cap stage at postnatal day 3.
      Osteoclasts were first visible at postnatal day 4 when the M3 came into close
      contact with the bone. The number of osteoclasts increased from postnatal day 8
      to postnatal day 12 to form a space for the growing tooth. The M3 had erupted by
      postnatal day 26. The M3, although smaller than the M1, passed through the same
      developmental stages over a similar time span but showed differences in
      initiation and in the timing of bone encapsulation.

PMID- 21726287
TI  - Clozapine-induced salivation: interaction with N-desmethylclozapine and
      amisulpride in an experimental rat model.
AB  - Many drugs (e.g. amisulpride) have been used to treat troublesome clozapine
      induced salivation; however, varying success has been achieved in this respect,
      probably because, until recently, the salivatory action of clozapine has been
      largely unexplained. In the rat, clozapine and its main metabolite, N
      desmethylclozapine, were found to exert mixed secretory actions: excitatory,
      through muscarinic acetylcholine M1-receptors giving rise to a long-lasting, low
      level flow of saliva; and inhibitory, through muscarinic M3-receptors and
      alpha(1) -adrenoceptors reducing the parasympathetically and sympathetically
      nerve-evoked flow of saliva. The aim of the present study was to define the
      interactions between clozapine and N-desmethylclozapine, and clozapine and
      amisulpride, with respect to the excitatory response. Submandibular glands,
      sensitized by chronic parasympathetic preganglionic denervation, were studied in
      pentobarbitone-anaesthetized rats. To prevent clozapine from being metabolized to
      N-desmethylclozapine by hepatic enzymes, the liver was, under terminal
      anaesthesia, excluded from the circulation. The weak receptor-stimulating
      clozapine prevented the strong receptor-stimulating N-desmethylclozapine, at
      specific ratios in humans and in rats, from exerting its full agonistic action.
      In conclusion, the contribution of N-desmethylclozapine to the clozapine-induced
      sialorrhoea was, at most, only partly additive. Furthermore, the present
      experimental set-up failed to demonstrate any anti-salivatory action of
      amisulpride on the clozapine-induced flow of saliva.

PMID- 21726288
TI  - The validity of self-reported dental agenesis.
AB  - The optimal tools for obtaining a diagnosis of dental agenesis (DA) among adults
      are childhood dental records and radiographs. However, these are often not
      available, and therefore the present study aimed to assess whether DA in adults
      could be validly assessed by self-reported information guided by a questionnaire.
      A questionnaire eliciting information on DA of permanent teeth was constructed,
      pilot-tested, and subsequently posted to a case group consisting of 334 young
      adults, for whom the DA status had been ascertained in the period from 1992 to
      2002. A control group, consisting of 258 young adults randomly selected from the
      population from which the cases originated, was also approached with
      questionnaires. The response rate was 53.7% among cases and 46.4% among controls.
      The sensitivity and specificity of self-reported DA were estimated to be at least
      0.88 (95% CI = 0.82-0.92) and 0.95 (95% CI = 0.89-0.98), respectively. These
      diagnostic test parameters are clearly inadequate for population-screening
      purposes. However, when screening patient groups with a higher occurrence of DA
      than is characteristic of the background population, the self-reported DA status
      may be a useful tool for identifying risk groups for conditions associated with
      the presence of DA.

PMID- 21726289
TI  - Exploring the associations between somatization and dental fear and dental
      visiting.
AB  - While somatization has been investigated as an important variable in relation to
      excessive health-service utilization, its role in relation to dental visiting and
      dental fear has received limited attention. It was hypothesized that an excessive
      focus on physical symptoms might lead somatizers to experience dental treatment
      as more traumatic, resulting in greater dental fear. The aims of this study were
      to determine whether somatization was associated with dental fear, reduced dental
      visiting, and symptomatic visiting. Questionnaire data were collected from 5,806
      dentate Finnish adults, with somatization measured using 12 items from the
      Symptom Check List (SCL-90). Dental fear was measured using a single-item
      question and dental visiting was assessed by questions relating to time since
      last dental visit and the usual reason for dental visiting. Multinomial logistic
      regression analyses indicated that somatization has a statistically significant
      positive association with both dental fear and symptomatic dental visiting after
      controlling for age, gender, and education. However, the association between
      dental-visiting frequency and somatization was not statistically significant. The
      results were consistent with the hypothesized role of somatization in the
      development of dental fear. Further investigation of how somatization is related
      to dental fear and dental-service utilization appears warranted.

PMID- 21726290
TI  - Does regional socioeconomic context affect the dental caries experience? A
      multilevel study of Korean adults.
AB  - Recent thinking about the role of regional socioeconomic context in generating
      health inequalities has argued for the collection of true 'area' data that
      accurately reflect the characteristics of a region. We investigated whether a
      range of attributes of regional environments, constructed from factor analysis of
      various regional socioeconomic indices, is associated with the dental caries
      experience of adults, and whether the nature of this association changes
      according to age. A linked data set comprising information on 6,402 individuals
      from the Korean National Oral Health Survey of 2000 and regional information from
      118 districts where our study population lived, were examined using multilevel
      analysis. The regional contextual variables, 'density of service and medical
      facilities' and 'dependence on manufacturing industry', were negatively
      associated with dental caries experience after controlling for individual
      characteristics, and these associations differed by age groups, especially in the
      older age group. Our findings suggest that hypotheses about specific chains of
      causation which might link service affluence or industrialization with dental
      caries need to be investigated further using more detailed indices.

PMID- 21726291
TI  - Influence of five neutralizing products on intra-oral pH after rinsing with
      simulated gastric acid.
AB  - The aetiology of dental erosion may be of both extrinsic and intrinsic origin.
      The aim of the present study was to test the ability of various neutralizing
      products to raise the low intra-oral pH after an erosive exposure, in this case
      to gastric acid, which was simulated using hydrochloric acid (HCl). Eleven adults
      participated. They rinsed with 10 ml of 10 mM HCl (pH 2) or 10 ml of 100 mM HCl
      (pH 1) for 1 min, after which the pH was measured intra-orally for up to 30 min
      at four sites (two approximal, one buccal, and the dorsum of the tongue). After
      rinsing with the two acid solutions (pH 1 and pH 2), the following products were
      used: (i) antacid tablet; (ii) gum arabic lozenge; (iii) mineral water; (iv)
      milk; and (v) tap water (positive control). The negative control was no product
      use. The five test products were used for 2 min after the erosive challenge. All
      the products produced an initially higher pH compared with the negative control.
      The antacid tablet resulted in the greatest and most rapid increase in pH,
      followed by the lozenge. In dental practice, the use of any of the neutralizing
      products tested, especially the antacid tablet, could be recommended in order to
      increase the intra-oral pH after an erosive challenge.

PMID- 21726292
TI  - 2-Hydroxyethyl methacrylate (HEMA) promotes IgG but not IgM antibody production
      in vivo in mice.
AB  - Individuals working in a dental clinic are exposed to 2-hydroxyethyl methacrylate
      (HEMA). HEMA has been found to have several effects on the immune system,
      including acting as an adjuvant in mice and stimulating the production of human
      IgG1 in vitro. In this study we continued to explore the immunomodulatory
      properties of HEMA in mice. Mice were co-injected subcutaneously with the
      following: HEMA + ovalbumin (OVA) in bicarbonate buffer, OVA in bicarbonate
      buffer, HEMA in bicarbonate buffer, or bicarbonate buffer alone. Mice immunized
      with OVA were killed 2 wk after a booster injection. Mice exposed to HEMA only
      were killed 6 d after the last injection with HEMA. Serum and spleens were
      collected. The activities of anti-OVA IgG and anti-OVA IgM were determined using
      ELISAs, as was the in vitro production of tumour necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) by splenocytes after 2 d of incubation.
      Splenocyte proliferation was analyzed using [(3) H]thymidine decomposition. Mice
      exposed twice to HEMA in vivo had a higher baseline and a higher concanavalin A
      stimulated proliferation of splenocytes, and produced less TNF-alpha in relation
      to IL-6, compared with controls. Immunization of mice with OVA/HEMA resulted in a
      higher anti-OVA IgG activity, relative to anti-OVA IgM activity, compared with
      controls. In conclusion, HEMA has selective effects on cytokine and antibody
      production in mice.

PMID- 21726293
TI  - Effect of ethanol-wet bonding with hydrophobic adhesive on caries-affected
      dentine.
AB  - Frequently encountered in clinical practice, caries-affected dentine (CAD) is the
      most challenging bonding substrate. This study evaluated the effect of ethanol
      wet bonding with hydrophobic adhesive to sound dentine and to CAD. In the control
      groups, prepared sound dentine and CAD were bonded with Adper Single Bond 2 using
      a traditional water-wet bonding technique. In the experimental groups, the
      specimens were treated as follows: Group 1, rinsed with stepwise ethanol
      dehydration; Group 2, immersion in 100% ethanol, three times, for 20 s each time;
      and Group 3, immersion in 100% ethanol for 20 s. Microtensile bond strength
      (MUTBS) testing was used to evaluate the effects of the different protocols on
      bonding. The microhardness of debonded dentine surfaces was measured to ensure
      the presence of CAD. Interfacial nanoleakage was evaluated by field-emission
      scanning electron microscopy. Treatment significantly improved the MUTBS in CAD
      in Groups 1 and 2, but had no effect on Group 3. Conversely, treatment
      significantly reduced the MUTBS in sound dentine in Groups 2 and 3, but had no
      effect in Group 1. The presence of nanoleakage varied with the ethanol-wet
      protocol used. In conclusion, ethanol-wet bonding can potentially improve bond
      efficacy to CAD when an appropriate protocol is used.

PMID- 21726294
TI  - Role of bonding agents in the repair of composite resin restorations.
AB  - Six commonly used composite resin materials and recommended bonding systems were
      tested to assess shear bond strength at the interface between aged and new
      composites with and without bonding. Test specimens were aged in water for 60 d
      before new composite was placed. Shear bond strength was assessed after 22 +/- 2
      h (Test 1) and after additional ageing by thermocycling (5-55 degrees C/5,000
      cycles) (Test 2). After an additional 180 d in water, the aged specimens were
      randomly divided into three groups to blind the test with respect to the aged
      composite. New composites were placed on aged specimens (two groups with and one
      without bonding agent) and thermocycled (Test 3). After 24 h (Test 1), the mean
      shear bond strength of the test specimens was 21-26 MPa when bonding agents were
      used, as opposed to 10-15 MPa without bonding agents. After thermocycling (Test
      2), the mean shear bond strength was 16-23 MPa with a bonding agent and 17 MPa
      without a bonding agent. After 180 d in water and subsequent thermocycling (Test
      3), the mean shear bond strength was 9-13 MPa with bonding agent and 2-3 MPa when
      no bonding agent was used. The results of this study therefore indicate that the
      use of bonding agents significantly improves the quality of composite repair.

PMID- 21726295
TI  - Effect of implant connection and restoration design (screwed vs. cemented) in
      reliability and failure modes of anterior crowns.
AB  - The mechanical performance of cemented or screw-retained implant-supported crowns
      with an internal or external configuration is yet to be understood. This in vitro
      study evaluated the effect of screw-retained and cement-retained prostheses on
      internal and external implant-abutment connections. Thereby, the reliability and
      failure modes of crowns were investigated. Eighty-four implants (Emfils; Colosso
      Evolution system) were divided into four groups (n=21 each): screw-retained and
      internal connection (Si), screw-retained and external connection (Se), cement
      retained and internal connection (Ci), and cement-retained and external
      connection (Ce). Ti-6Al-4V abutments were torqued (30 Ncm) to the implants, and
      maxillary central incisor metal crowns were torqued (30 Ncm) or cemented (Rely X
      Unicem; 3M-ESPE) and subjected to accelerated life-testing in water. Use-level
      probability Weibull curves and reliability for 50,000 cycles at 150 N were
      calculated. The beta values for Si (1.72), Se (1.50), Ci (1.34), and Ce (1.77)
      groups indicated that fatigue/damage accumulation accelerated their failure. The
      Ci group presented the highest reliability, the Se group presented the lowest
      reliability, and Si and Ce groups presented intermediate reliability. Screw
      retained restorations presented mainly abutment fracture. Cement-retained
      restorations resulted in failures of the screw in the Ce group, but implant/screw
      fracture in the Ci group.

PMID- 21726297
TI  - Addressing malnutrition: is it time for new approaches?

PMID- 21726301
TI  - Manual or semi-automated edge detection of the maximal far wall common carotid
      intima-media thickness: a direct comparison.
AB  - BACKGROUND: Automated edge detection is thought to be superior to manual edge
      detection in quantification of the far wall common carotid intima-media thickness
      (CIMT), yet published evidence making a direct comparison is not available.
      METHODS: Data were used from the METEOR study, a randomized placebo-controlled
      trial among 984 individuals showing that rosuvastatin attenuated the rate of
      change of 2 year change in CIMT among low-risk individuals with subclinical
      atherosclerosis. For this post hoc analysis, CIMT images of the far wall of the
      common carotid artery were evaluated using manual and semi-automated edge
      detection and reproducibility, relation to cardiovascular risk factors, rates of
      change over time and effects of lipid-lowering therapy were assessed. RESULTS:
      Reproducibility was high for both reading methods. Direction, magnitude and
      statistical significance of risk factor relations were similar across methods.
      Rate of change in CIMT in participants assigned to placebo was 0.0066 mm per year
      (SE: 0.0027) for manually and 0.0072 mm per year (SE: 0.0029) for semi
      automatically read images. The effect of lipid-lowering therapy on CIMT changes
      was -0.0103 mm per year (SE: 0.0032) for manual reading and -0.0111 mm per year
      (SE: 0.0034) for semi-automated reading. CONCLUSION: Manual and semi-automated
      readings of the maximal far wall of the common CIMT images both result in high
      reproducibility, show similar risk factor relations, rates of change and
      treatment effects. Hence, choices between semi-automated and manual reading
      software for CIMT studies likely should be based on logistical and cost
      considerations rather than differences in expected data quality when the choice
      is made to use far wall common CIMT measurements.

PMID- 21726302
TI  - Combined clopidogrel and proton pump inhibitor therapy is associated with higher
      cardiovascular event rates after percutaneous coronary intervention: a report
      from the BASKET trial.
AB  - OBJECTIVE: To investigate whether there is an increased risk of cardiac events
      with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after
      percutaneous coronary intervention (PCI). DESIGN: In the BAsel Stent Kosten
      Effektivitats Trial (BASKET), all patients undergoing PCI received 6 months of
      clopidogrel and were analysed for the use of PPI therapy. Endpoints were major
      adverse cardiac events (MACE), myocardial infarction (MI), death and target
      vessel revascularization (TVR) after 36 months. RESULTS: Of 801 patients with
      available discharge medication data, 109 (14%) received PPIs. Patients who
      received PPIs were older (66.5 +/- 10.5 vs. 63.3 +/- 11.3 years, P = 0.006), more
      likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6%
      vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P =
      0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs.
      2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin
      (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients
      who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027)
      and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P =
      0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By
      multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07
      3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the
      only independent risk factors for MI. CONCLUSION: In a real-world PCI population,
      the combination of PPIs and clopidogrel was associated with a doubling of MI
      rates after 3 years. Even after correction for confounding factors, concomitant
      PPI use remained an independent predictor of outcome emphasizing the clinical
      importance of this drug-drug interaction.

PMID- 21726303
TI  - Trouble with translational medicine and bad news for mice.

PMID- 21726304
TI  - Screening for hepatocellular carcinoma in acute intermittent porphyria.

PMID- 21726305
TI  - Haemoglobin A1c in donor erythrocytes.

PMID- 21726306
TI  - Alcohol, the heart and the cardiovascular system: what do we know and where
      should we go?

PMID- 21726307
TI  - Stress-coping morbidity among family members of addiction patients in Singapore.
AB  - INTRODUCTIONS AND AIMS: Research from western countries indicates that family
      members of addiction patients report heightened stress and psychological
      morbidity. This current study aimed to examine stress, coping behaviours, related
      morbidity and subsequent resource utilisation among family members of patients
      attending a national treatment program in Singapore. DESIGN AND METHODS: The
      study used a matched case-control design. One hundred family members of addiction
      patients attending treatment and 100 matched controls completed a semi-structured
      interview with a researcher. This included the Beck Depression Inventory-II,
      Short-Form Health Survey-36, General Health Questionnaire-28, Perceived Stress
      Scale, Family Member Impact Scale and Coping Questionnaire, and also assessed
      service utilisation. RESULTS: T-tests revealed significantly greater depression,
      stress and psychiatric morbidity and poorer overall well-being (Short-Form Health
      Survey-36) among family members compared with controls. Despite the apparent
      negative impact on mental health, their physical morbidity did not differ from
      controls and services utilisation was low. Tolerant-inactive coping was found to
      be most strongly correlated with psychological well-being. Multivariate analysis
      indicated that perceived stress was the strongest predictor of overall strain
      (General Health Questionnaire), but this was not moderated by coping style.
      DISCUSSION AND CONCLUSIONS: Subjective appraisal of stress and coping responses
      are essential factors affecting the morbidity of family members. Family members
      demonstrated a need and willingness to engage in formal treatment/counselling for
      their own problems that were attributed to living with an addiction patient. This
      provides an opportunity for stress management and brief interventions to modify
      coping styles, thereby minimizing the potential negative mental health impact on
      family members.

PMID- 21726308
TI  - Methadone prescribing under supervised consumption on premises: a Scottish
      clinician's perspective on prescribing practice.
AB  - INTRODUCTION AND AIMS: Specialist services have increased their capacity
      considerably in recent years to initiate and/or provide ongoing treatment for
      drug misuse. Consequently, methadone prescribing has substantially increased and
      over 17,000 patients are currently receiving methadone. Clinical guidance
      promotes consumption on the premises (COP) initially to ensure patients take
      medication as prescribed and also to prevent diversion. Diversion poses two
      risks: the patient may remain under-treated and continue illicit heroin use;
      diverted drugs put others at risk. However, COP can be restrictive. Current UK
      guidance is vague and not evidence-based recommending 'around three months
      subject to assessment of compliance and individual circumstances'. The overall
      aim of this study was to describe clinical practice regarding prescribing
      methadone under COP in Scotland, and reasons for this. Design and Methods. A
      structured, postal questionnaire was sent to all lead clinicians in specialist
      drug treatment centres in Scotland in 2009 (n=42). The questionnaire explored
      current practice, influence of supervision on retention, views of best practice
      and contingency management. RESULTS: The response rate was 76% (n=32). Clinicians
      usually supervise for a minimum of three months with patient-centred criteria
      used to determine when to reduce or stop COP. Employment, clinical stability,
      family support and concerns for the safety of children in the home influenced
      decision making. Contingency management approaches to supervision were widely
      used (62%). DISCUSSION AND CONCLUSION: In Scotland, clinicians' practice is
      variable and individualised to patients, but generally cautious regarding
      relaxing supervision conditions. This may reflect the lack of evidence-based
      guidance.

PMID- 21726309
TI  - A spatial analysis of the moderating effects of land use on the association
      between alcohol outlet density and violence in urban areas.
AB  - AIMS: While there is substantial evidence of an association between alcohol
      outlet density and assault, it is unlikely this association is constant across
      the urban environment. This study tested the moderating influence of land use on
      the outlet-violence association. DESIGN: Cross-sectional ecological study that
      controlled for spatial autocorrelation. SETTING, PARTICIPANTS AND MEASUREMENTS:
      Police-recorded data on simple and aggravated assaults were obtained for all 302
      block groups (mean population = 1038) in Cincinnati, Ohio, USA. Addresses of
      alcohol outlets for Cincinnati were obtained from the Ohio Division of Liquor
      Control, geocoded to the street level, and aggregated to census block groups.
      Data on eight categories of land use were obtained from the Cincinnati Area
      Geographic Information System, with location quotients computed for each block
      group. FINDINGS: We found substantial evidence that the impact of total alcohol
      outlet density, bar density and carryout density on assault density was moderated
      by land use. CONCLUSIONS: By taking into account local characteristics, policy
      makers can make more informed decisions when regulating the placement and density
      of alcohol licenses in urban areas. Similarly, more systematic knowledge of how
      the association between alcohol outlet density and assault varies across the
      urban landscape should reduce harm and promote responsible retailing.
      Nevertheless, ours is one of the first studies to address the moderating effect
      of land use and we encourage further research to test the stability and
      generalisability of our results.

PMID- 21726310
TI  - The nature and strength of the relationship between expenditure on alcohol and
      food: an analysis of adult-only households in the UK.
AB  - INTRODUCTION AND AIMS: Unhealthy lifestyle behaviours can cluster to produce more
      detrimental overall health consequences than expected with a simple additive
      effect. This study aims to expand current knowledge of the nature and strength of
      the relationship between two such health behaviours, alcohol and diet, through
      analysis of household expenditure on food and drink from a nationally
      representative UK sample. DESIGN AND METHODS: Data from the Expenditure and Food
      Survey for 2005-2006 was used to analyse expenditure on alcohol and diet for 3146
      UK households. The classification of a food as healthy or unhealthy was
      determined using dietary advice provided by the Food Standards Agency. Alcohol
      expenditure was disaggregated into spending in pubs, bars, clubs and restaurants
      (on-trade expenditure) and spending in off-licenses and supermarkets (off-trade
      expenditure). Analyses were stratified according to household disposable income
      quintile and household beverage preference. RESULTS: As household expenditure on
      alcohol increases, spending on both healthy and unhealthy food decreases. Higher
      income households spend proportionately more on on-trade alcohol and healthy food
      than lower income households, and less on unhealthy food. Off-trade alcohol
      expenditure does not differ significantly according to household income.
      Households that prefer to purchase wine have healthier expenditure patterns than
      those that prefer to buy beer or spirits, even after controlling for income.
      DISCUSSION AND CONCLUSIONS: Low-income households and those that purchase more
      beer or spirits than wine could be targeted for health promotion interventions to
      reduce their risk of negative health outcomes from the clustering of alcohol
      consumption and unhealthy diet.

PMID- 21726311
TI  - Predisposed violent drug users versus drug users who commit violence: does the
      order of onset translate to differences in the severity of violent offending?
AB  - INTRODUCTION AND AIMS: To determine whether there were differences in drug use
      profiles, psychopathology, and severity of violence among regular illicit drug
      users in respect to the order of onset of drug use and violence. DESIGN AND
      METHODS: A cross-sectional survey utilising self-report data was administered to
      327 regular illicit drug users in Sydney, Australia. RESULTS: Those who first
      committed violent crime prior to illicit drug use were found to have more serious
      offending patterns (greater frequency, arrest for more serious violence, earlier
      age of onset, and more weapon use). Being male, having a history of child abuse
      and greater severity of conduct disorder were independent predictors of
      committing violence before drug use. DISCUSSION AND CONCLUSIONS: Whilst the
      nature of the data does not permit causative conclusions, it appears that the
      order of onset of illicit drug use and violent crime is associated with
      heterogeneous offending patterns. Early onset violence was associated with more
      severe violent crimes in later adulthood, whereas violence which proceeded drug
      use was more strongly linked to systemic risks. The findings have implications
      for early intervention among children with conduct disorder and also for using
      drug and alcohol treatment services to reduce specific risks associated with
      violence.

PMID- 21726312
TI  - Brief alcohol screening in a clinical psychiatric population: special attention
      needed.
AB  - INTRODUCTION AND AIMS: Abbreviated versions of the Alcohol Use Disorders
      Identification Test (AUDIT) and single-item screeners show promising results but
      have not previously been investigated in a clinical psychiatric setting. The aim
      of the present study was to investigate the capacity of three brief screening
      methods to detect hazardous drinking in a psychiatric treatment-seeking
      population. DESIGN AND METHODS: Data were collected from consecutive patients (n
      = 1811) visiting a general psychiatric clinic. The screening capacity of the
      heavy episodic drinking (HED) screener, AUDIT item # 3 (AUDIT-3) and the three
      consumption items of AUDIT (AUDIT-C) was compared to the result of the full 10
      item AUDIT with cut-off points 6 for women and 8 for men. RESULTS: The HED
      screener and AUDIT-3 with recommended cut-offs captured low rates of hazardous
      drinkers when compared to the full AUDIT. Lowering the cut-offs created rates far
      above those of the full AUDIT. AUDIT-C with recommended cut-off limits
      categorised nearly the same rates of men as the full AUDIT but much higher rates
      of women. Raising the cut-off for women approached the detection rate of AUDIT-C
      closely to that of the full AUDIT. DISCUSSION AND CONCLUSIONS: The findings of
      this study suggest that the HED screener is not sensitive enough in the clinical
      psychiatric setting. When designing alcohol screening measures to be used all
      over health-care organisations, special attention should be paid to psychiatric
      patients. If a somewhat more extensive screening tool is used, the full AUDIT is
      recommended.

PMID- 21726313
TI  - A literature review of the impact of a diagnosis of cancer of the vulva and
      surgical treatment.
AB  - AIMS AND OBJECTIVES: This paper examines the evidence available regarding the
      physical, psychological and sexual consequences for women following a diagnosis
      and treatment for cancer of the vulva. BACKGROUND: Cancer of the vulva is a rare
      condition affecting approximately 1000 women in the UK each year. However, little
      is known about the impact of the condition as there is a limited research base to
      inform clinical practice. DESIGN: Review. METHOD: This paper critiques the 15
      studies identified in the English language literature relating to carcinoma of
      the vulva from 1983 to the present. Collectively these involved less than 400
      women with this condition. RESULTS: The review highlighted a paucity of published
      studies on this patient group. There are weaknesses in the design and analytical
      methods of the studies and a lack of clarity in the analysis of the published
      data. However, the review has enabled a picture to be built up of the challenges
      these women face postoperatively. The lack of recent evidence to support care
      practices offers limited help in contemporary health care today. CONCLUSION:
      There is a clear need for further research to explore the issues for women facing
      treatment for carcinoma vulva. RELEVANCE TO CLINICAL PRACTICE: An awareness of
      the issues facing women following a diagnosis and subsequent treatment, usually
      surgery, for cancer of the vulva will allow nurses and other health care
      professionals to have a greater understanding of the needs of these women and
      thus impact on care planning.

PMID- 21726314
TI  - Nursing research capacity building in a Spanish hospital: an intervention study.
AB  - AIMS AND OBJECTIVES: To evaluate a contextually framed intervention to increase
      nursing research capacity among clinical nurses in a Spanish hospital.
      BACKGROUND: In Spain, there has been a paucity of nursing research and a lack of
      nursing research culture. Currently, with the European Convergence of educational
      programmes and qualifications, there is a growing interest in promoting nursing
      research in this country. DESIGN: A quasi-experimental design. METHODS: Using a
      control (n = 81) and an intervention group (n = 89) of nurses, pre- and
      postintervention data were collected from both groups to evaluate the impact of
      the intervention at three times. The intervention, implemented over one year,
      consisted of the establishment of a mentors' network and an educational programme
      with research courses and journal clubs. Data collection methods included
      questionnaires, objective tests and scales. RESULTS: The nursing research
      capacity of the hospital developed moderately after the intervention, with an
      increase in participants' research capability (knowledge, skills and attitudes)
      and a decrease in some of the inhibiting factors identified in the context.
      CONCLUSIONS: A new comprehensive and contextually framed intervention to develop
      nursing research capacity has been designed, implemented and evaluated in a
      hospital. It contributed to the development of the nursing research culture in
      the context. Relevance to clinical practice.  An increase in nursing research
      activity could improve the quality of nursing care through the incorporation of
      research evidence in practice. This intervention could be used as a model in
      other hospitals, and it should be evaluated in other contexts.

PMID- 21726315
TI  - Parental report of sleep problems in Down syndrome.
AB  - BACKGROUND: Children with Down syndrome (DS) suffer from sleep problems,
      including sleep maintenance problems, as well as snoring, and other symptoms of
      disordered breathing. To examine sleep in DS, we gave parents a questionnaire
      assessing their child's sleep. MATERIALS AND METHODS: The parents of 35 children
      with DS (mean age = 12.65 years, range = 7-18 years) completed the 33-item
      Children's Sleep Habits Questionnaire. RESULTS: Eighty-five per cent of our
      sample had sleep disturbance scores in the clinical range (mean = 48.63, SD =
      7.15, range = 34-64). Our sample also had significantly elevated scores on the
      Bedtime Resistance, Sleep Anxiety, Night Wakings, Parasomnias, Sleep Disordered
      Breathing and Daytime Sleepiness subscales. CONCLUSIONS: Children with DS are at
      risk for developing symptoms of sleep disordered breathing, and may have
      additional sleep problems that are unrelated to sleep disordered breathing.

PMID- 21726316
TI  - The impact of health checks for people with intellectual disabilities: a
      systematic review of evidence.
AB  - BACKGROUND: Health checks for people with intellectual disabilities (ID) have
      been recommended as one component of health policy responses to the poorer health
      of people with ID. This review summarises evidence on the impact of health checks
      on the health and well-being of people with ID. METHODS: Electronic literature
      searches and email contacts were used to identify literature relevant to the
      impact of health checks for people with ID. RESULTS: A total of 38 publications
      were identified. These involved checking the health of over 5000 people with ID
      from a range of countries including a full range of people with ID. Health checks
      consistently led to detection of unmet health needs and targeted actions to
      address health needs. CONCLUSIONS: Health checks are effective in identifying
      previously unrecognised health needs, including life-threatening conditions.
      Future research should consider strategies for optimising the cost-effectiveness
      or efficiency of health checks.

PMID- 21726317
TI  - BMI and attitudes and beliefs about physical activity and nutrition of parents of
      adolescents with intellectual disabilities.
AB  - BACKGROUND: The purpose of this study was: (1) to evaluate the beliefs, attitudes
      and behaviours associated with nutrition and physical activity of parents with
      adolescents with intellectual disabilities (ID); (2) to determine if these
      variables related to the body mass index (BMI) of the adolescents and the
      parents' BMI; and (3) to investigate if the parents' perception of their child's
      weight status was accurate. METHODS: A survey was used to collect information on
      BMI and attitudes and beliefs about nutrition and physical activity from parents
      (n = 207) of adolescents with ID attending schools participating in the Best
      Buddies Program. RESULTS: Approximately 45% of the adolescents were overweight or
      obese and over two-thirds of the parents were either overweight or obese. There
      was a significant difference in child's BMI by parents' description, F(3,158) =
      72.75, P < 0.001. Factor analysis on questions on physical activity and nutrition
      revealed three factors (Factor 1 - Family Healthy Habits, Factor 2 - Parental
      Role and Factor 3 - Parental Activity) extracting 63% of the variance. The BMI of
      the adolescents significantly correlated with Factors 2 and 3. Children
      categorised as having a lower BMI had parents who agreed significantly more (r = 
      0.22, P < 0.005) with questions about being role models. There was a significant
      correlation between BMI for both the parents and adolescents and frequency of
      fast foods purchased. CONCLUSION: Efforts need to be made to provide parents of
      adolescents with ID tailored information about how they can assist their child in
      managing their weight. This information should emphasise to parents the important
      part they play as role models and as providers for healthy choices for physical
      activity as well as nutrition.

PMID- 21726318
TI  - The relationship between challenging behaviour, burnout and cognitive variables
      in staff working with people who have intellectual disabilities.
AB  - BACKGROUND: There is evidence to suggest a relationship between the way in which
      staff perceive challenging behaviour and burnout in staff working with people
      with intellectual disabilities (ID) and challenging behaviour. However, the
      evidence of a direct link is equivocal and it is possible that a number of
      different variables mediate this relationship. The aim of the study is to confirm
      whether there is a relationship between challenging behaviour and staff burnout,
      and in addition, to test whether staff perceptions about challenging behaviour
      mediate this relationship. METHOD: Seventy-eight staff completed measures of
      burnout, challenging behaviour and perceptions about challenging behaviour. The
      perceptions explored included beliefs about the timeline of behaviour, staff's
      perception of whether they themselves have control over the behaviour, beliefs
      about clients' ability to control the behaviour and staff's negative emotional
      responses. RESULTS: Significant positive correlations were found between
      challenging behaviour and burnout, challenging behaviour and cognitive variables,
      and cognitive variables and burnout. Regression analyses demonstrated that
      negative emotions mediate the relationship between challenging behaviour and
      burnout. CONCLUSIONS: The results show evidence that there is a relationship
      between challenging behaviour and burnout that is mediated by negative emotion,
      namely the fear of potential assault.

PMID- 21726319
TI  - The impact of living arrangements and deinstitutionalisation in the health status
      of persons with intellectual disability in Europe.
AB  - BACKGROUND: Despite progress in the process of deinstitutionalisation, very
      little is known about the health conditions of people with intellectual
      disability (PWID) who live in large institutions and PWID living in small
      residential services, family homes or independent living within the community.
      Furthermore, there are no international comparison studies at European level of
      the health status and health risk factors of PWID living in fully staffed
      residential services with formal support and care compared with those living in
      unstaffed family homes or independent houses with no formal support. METHODS: A
      total of 1269 persons with ID and/or their proxy respondents were recruited and
      face-to-face interviewed in 14 EU countries with the P15, a multinational
      assessment battery for collecting data on health indicators relevant to PWID.
      Participants were grouped according to their living arrangements, availability of
      formal support and stage of deinstitutionalisation. RESULTS: Obesity and
      sedentary lifestyle along with a number of illnesses such as epilepsy, mental
      disorders, allergies or constipation were highly prevalent among PWID. A
      significantly higher presence of myocardial infarctions, chronic bronchitis,
      osteoporosis and gastric or duodenal ulcers was found among participants in
      countries considered to be at the early stage of deinstitutionalisation.
      Regardless of deinstitutionalisation stage, important deficits in variables
      related to such medical health promotion measures as vaccinations, cancer
      screenings and medical checks were found in family homes and independent living
      arrangements. Age, number of people living in the same home or number of places
      in residential services, presence of affective symptoms and obesity require
      further attention as they seem to be related to an increase in the number of
      illnesses suffered by PWID. DISCUSSION: Particular illnesses were found to be
      highly prevalent in PWID. There were important differences between different
      living arrangements depending on the level of formal support available and the
      stage of deinstitutionalisation. PWID are in need of tailored primary health
      programs that guarantee their access to quality health and health promotion and
      the preventative health actions of vaccination programs, systematic health
      checks, specific screenings and nutritional controls. Extensive national health
      surveys and epidemiological studies of PWID in the EC member states are urgently
      needed in order to reduce increased morbidity rates among this population.

PMID- 21726320
TI  - Utility of the Brief Symptom Inventory (BSI) in psychiatric outpatients with
      intellectual disabilities.
AB  - BACKGROUND: Diagnostics and care for people with intellectual disabilities (ID)
      and psychiatric disorders need to be improved. This can be done by using
      assessment instruments to routinely measure the nature and severity of
      psychiatric symptoms. Up until now, in the Netherlands, assessment measures are
      seldom used in the psychiatric care for this population. The objective of the
      present paper is to evaluate the use of the Brief Symptom Inventory (BSI), a
      widely used standardised questionnaire in general psychiatry, in a well-defined
      sample of people with borderline intellectual functioning or mild ID diagnosed
      with one or more psychiatric disorders. METHODS: A total of 224 psychiatric
      outpatients with either borderline intellectual functioning or mild ID
      participated in this study. All participants were new patients of Kristal, Centre
      for Psychiatry and Intellectual Disability in the Netherlands, in the period
      between 1 April 2008 and 1 October 2009. All participants were assessed by a
      multidisciplinary team, including a certified psychiatrist. Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV-TR) criteria were applied. The
      mean total intelligence quotient was measured with the Wechsler Adult
      Intelligence Scale (WAIS-III). The BSI was administered in an assisted fashion.
      Utility and psychometric properties of the BSI were investigated. Internal
      consistency coefficients (Cronbach's alphas) were computed. Bivariate
      correlations between the sub-scales were computed to assess differentiation
      between the scales. Mean sub-scale scores were compared between different DSM-IV
      TR subgroups to investigate the discriminant abilities of the scales. A
      confirmatory factor analysis was conducted. RESULTS: The results suggest that the
      BSI is practically useful. Internal consistencies ranged from 0.70 to 0.96 and
      thus are considered good to adequate. Sub-scale inter-correlations showed there
      is a degree of differentiation between the sub-scales. Discriminant validity was
      shown for the sub-scales depression, anxiety and phobic anxiety. Confirmatory
      factor analysis showed that the underlying structure of the BSI could be
      described by the same nine-factor model as reported in previous studies.
      CONCLUSIONS: As a result of the psychometric properties illustrated, this study
      supports the use of the BSI as a screener for psychopathology and a general
      outcome measure in people with ID.

PMID- 21726321
TI  - Children born to women with intellectual disabilities - 5-year incidence in a
      Swedish county.
AB  - BACKGROUND: Families with parental intellectual disabilities (ID) are likely to
      need support in achieving a decent family life. In order to accurately plan for
      such support services, society needs data regarding the occurrence of those
      parents and their children. The aim of this study was to investigate the 5-year
      incidence of children born to women with ID in a county in Sweden. METHODS: Women
      born between 1975 and 1989 were identified from school registers for children and
      adolescents with ID in the county of Blekinge. The women's personal
      identification numbers were, in 2010, linked and matched with the Swedish Medical
      Birth Register. RESULTS: In total, 98 women with ID were identified. Nine of
      these had given birth to children; one woman to two children and eight women to
      one child each. The 10 children were born between 2004 and 2008. CONCLUSION: The
      incidence rate calculated as a result of the present study indicates that
      approximately 2.12 per 1000 children are born per year to women with ID. For the
      whole of Sweden that rate indicates an incidence of approximately 225 children
      each year. On the basis of this, the prevalence of children (aged 0-18 years)
      being born to women with ID is estimated at about 4050.

PMID- 21726322
TI  - Variability of self-regulatory strategies in children with intellectual
      disability and typically developing children in pretend play situations.
AB  - OBJECTIVE: This study has examined whether or not self-regulatory strategies vary
      depending on pretend play situations in 40 children with intellectual disability
      and 40 typically developing children. METHOD: Their cognitive, linguistic and
      individual symbolic play levels were assessed in order to match the children of
      the two groups. During two dyadic pretend play sessions (Itinerary, Creativity),
      their abilities in dyadic pretend play and in self-regulation were assessed by
      coding their behaviour via two validated grids. RESULTS: The results showed
      similar overall levels in dyadic pretend play in both groups but a lower
      involvement was observed in disabled children. Some specific deficits and
      strengths in self-regulatory strategies were highlighted in children with
      intellectual disability. In both groups, non-structured Creativity situation
      induced weaker abilities in pretend play, and better self-evaluation strategy
      than in the structured Itinerary situation. In both groups, positive links
      between specific self-regulation strategies (identification of objective,
      planning, self-regulated attention, self-motivation, self-evaluation) and
      specific dyadic pretend play abilities (involvement, roles, actions, objects,
      social participation) are more numerous and higher in the structured Itinerary
      situation than in the Creativity situation.

PMID- 21726323
TI  - Working memory in Down syndrome: is there a dual task deficit?
AB  - BACKGROUND: Recent studies have shown that individuals with Down syndrome (DS)
      are poorer than controls in performing verbal and visuospatial dual tasks. The
      present study aims at better investigating the dual task deficit in working
      memory in individuals with DS. METHOD: Forty-five individuals with DS and 45
      typically developing children matched for verbal mental age completed a series of
      verbal and visuospatial working memory tasks, involving conditions that either
      required the combination of two tasks in the same modality (verbal or visual) or
      of cross-modality pairs of tasks. RESULTS AND CONCLUSIONS: Two distinct deficits
      were found in individuals with DS: impairment in verbal tasks and further
      impairment in all dual task conditions. The results confirm the hypothesis of a
      central executive impairment in individuals with DS.

PMID- 21726324
TI  - Duty of care and autonomy: how support workers managed the tension between
      protecting service users from risk and promoting their independence in a
      specialist group home.
AB  - BACKGROUND: In the UK those paid to support adults with intellectual disabilities
      must manage two potentially conflicting duties that are set out in policy
      documents as being vital to their role: protecting service users (their duty of
      care) and recognising service users' autonomy. This study focuses specifically on
      the support of people with the genetically determined condition, Prader-Willi
      syndrome (PWS). Due to the behaviours associated with PWS, the support of this
      group of people vividly illustrates the tension between respect for autonomy and
      duty of care. This article explores how support workers working in a residential
      group home managed their competing duties of managing risk and promoting
      independence in practice. METHODS: An ethnographic study, comprising of
      qualitative observations, semi-structured interviews and documentary analysis,
      was undertaken to investigate the work of support workers in a UK residential
      group home specialising in the support of adults diagnosed with PWS. The study
      focused on how support workers attempted to reconcile the tension between
      protecting service users from the risks associated with the syndrome and
      acknowledging service users' autonomy by enabling independence. RESULTS: Findings
      demonstrate that risk was central to the structure of care delivery at the group
      home and support workers often adhered to standardised risk management
      procedures. The organisation also required support workers to promote service
      users' independence and many thought acknowledging service users' autonomy
      through the promotion of their independence was important. To manage tensions
      between their differing duties, some support workers deviated from standardised
      risk management procedures to allow service users a degree of independence.
      CONCLUSIONS: There is a tension between the duty of care and the duty to
      recognise autonomy at the level of service delivery in residential homes. Support
      workers attempt to manage this tension; however, further work needs to be done by
      both residential services and policy makers to facilitate the reconciliation of
      the duty of care with the duty to recognise service users' autonomy in practice.

PMID- 21726325
TI  - Social integration of people with intellectual disability: insights from a social
      psychological research programme.
AB  - BACKGROUND: Social integration of people with intellectual disability (ID) moving
      into regular neighbourhoods tends to be studied and evaluated without detailed
      knowledge about the social psychological aspects of everyday interaction between
      neighbours with and without ID. The goal of the present paper is to show how the
      authors' social psychological research programme may contribute to this field of
      inquiry. METHODS: The different ways in which societies respond to features and
      behaviours that may be perceived as deviant are theoretically analysed. Results
      of empirical studies are reported to clarify how social responses to people with
      ID are special in terms of perceptions, emotions and interaction desires of
      people with and without ID during a pre-contact and contact phase. RESULTS: On
      the basis of the theoretical analysis, it is concluded that regular neighbouring
      in modern Western society often takes the form of benevolent tolerance, rather
      than stigmatisation and prejudice. However, empirical studies reveal that, prior
      to getting people with ID as new neighbours, prospective neighbours without ID
      experience a specific pattern of emotions that are associated with specific
      desires (e.g. with respect to information supply or a caring relationship). These
      anticipatory reactions are dependent on the expected size of the group moving in
      and on the severity of ID. Furthermore, while actually engaging in neighbouring,
      neighbours with and without ID appear to have experiences related to behaviour of
      residents, staff and features of housing facilities that are perceived as
      (in)congruent with regular neighbouring. CONCLUSIONS: It is concluded that
      interpersonal relationships between neighbours with and without ID should not be
      simplified in terms of attitudes that would be primarily prejudiced/stigmatising
      versus entirely accepting. Rather, our studies paint a more complex picture of
      sometimes ambivalent thoughts, feelings and interaction needs that all should be
      taken into account to make social integration a success.

PMID- 21726326
TI  - The prevalence of low self-esteem in an intellectually disabled forensic
      population.
AB  - BACKGROUND: This was a quantitative study to measure the prevalence low self
      esteem in an intellectually disabled forensic population. The dependent variables
      used were the adapted six-item Rosenberg Self-Esteem Scale and the adapted
      Evaluative Beliefs Scale. It had a repeated measures design with independent
      variables including consideration of differences between the low and medium
      secure parts of the service, the influences of types of offences and the effects
      of disrupted childhood attachments. METHODS: Forty-four male clients, with mild
      to borderline intellectual disabilities, were recruited. Data were collected by
      one key researcher during individual research interviews using the two structured
      instruments to measure self-esteem. Further data were then obtained from
      routinely recorded clinical information held on the hospital computer system.
      RESULTS: Unexpectedly, the majority of clients scored as having moderate or high
      self-esteem on both self-esteem measures. There was a statistically significant
      positive correlation between the two scales. In all, 64% of the population
      studied had committed either sexual offences or fire setting offences. Contrary
      to expectation, those who had evidence of disrupted attachments had slightly
      higher self-esteem than those who had not experienced disrupted attachments.
      CONCLUSIONS: Self-esteem is a complex personal concept with many influencing
      factors. Cognitive behaviour therapy has a unique role in realising and
      overcoming negative core beliefs and feelings of low self-worth. The offence
      types concurred with previously noted patterns of offending within the
      intellectually disabled forensic population.

PMID- 21726327
TI  - Staff interactive style during multisensory storytelling with persons with
      profound intellectual and multiple disabilities.
AB  - BACKGROUND: Multisensory storytelling (MSST) is an individualised activity for
      people with profound intellectual and multiple disabilities (PIMD) in which a
      story is being told with an emphasis on sensory experiences and social
      interaction. MSST is a promising approach, but needs more empirical research
      evidence. In general, there is a lack of research about staff interaction during
      specific activities with people with PIMD. In the present study, we explored the
      possibility to describe staff interactive style during MSST making use of a
      global coding instrument. METHODS: Twenty dyads of a person with PIMD and a
      professional caregiver participated in an observation study. The caregivers
      received training in MSST and told a multisensory story to their client once a
      week, for a period of 10 weeks. The first, fifth and last session were recorded
      on video. Staff interactive style was coded using an adapted version of the
      Maternal Behavior Rating Scale, with a consensus rating procedure. RESULTS:
      Professional caregivers scored moderately on the Maternal Behavior Rating Scale.
      Repeated measures analyses showed no change in time. We did not find a
      relationship between staff interactive style and client or staff characteristics.
      CONCLUSIONS: The Maternal Behavior Rating Scale contributes to our understanding
      of staff interactive style during activities with people with PIMD. Specifically
      for MSST, the moderate scores on the interactive style dimensions were
      unexpected, because the individualised MSST activity created an optimal situation
      for high-quality interaction with people with PIMD. Because the interactive style
      did not improve through the repetition of the activity either, these results
      might point to a need for staff training in achieving high-quality interaction
      during activities like MSST.

PMID- 21726328
TI  - Determinants of distribution and prevalence of avian malaria in blue tit
      populations across Europe: separating host and parasite effects.
AB  - Although avian malarial parasites are globally distributed, the factors that
      affect the geographical distribution and local prevalence of different parasite
      lineages across host populations or species are still poorly understood. Based on
      the intense screening of avian malarial parasites in nine European blue tit
      populations, we studied whether distribution ranges as well as local adaptation,
      host specialization and phylogenetic relationships can determine the observed
      prevalences within populations. We found that prevalence differed consistently
      between parasite lineages and host populations, indicating that the transmission
      success of parasites is lineage specific but is partly shaped by locality
      specific effects. We also found that the lineage-specific estimate of prevalence
      was related to the distribution range of parasites: lineages found in more host
      populations were generally more prevalent within these populations. Additionally,
      parasites with high prevalence that were also widely distributed among blue tit
      populations were also found to infect more host species. These findings suggest
      that parasites reaching high local prevalence can also realize wide distribution
      at a global scale that can have further consequences for host specialization.
      Although phylogenetic relationships among parasites did not predict prevalence,
      we detected a close match between a tree based on the geographic distance of the
      host populations and the parasite phylogenetic tree, implying that neighbouring
      host populations shared a related parasite fauna.

PMID- 21726329
TI  - The effect of a population bottleneck on the evolution of genetic
      variance/covariance structure.
AB  - It is well known that standard population genetic theory predicts decreased
      additive genetic variance (V(a) ) following a population bottleneck and that
      theoretical models including interallelic and intergenic interactions indicate
      such loss may be avoided. However, few empirical data from multicellular model
      systems are available, especially regarding variance/covariance (V/CV)
      relationships. Here, we compare the V/CV structure of seventeen traits related to
      body size and composition between control (60 mating pairs/generation) and
      bottlenecked (2 mating pairs/generation; average F = 0.39) strains of mice.
      Although results for individual traits vary considerably, multivariate analysis
      indicates that V(a) in the bottlenecked populations is greater than expected.
      Traits with patterns and amounts of epistasis predictive of enhanced V(a) also
      show the largest deviations from additive expectations. Finally, the correlation
      structure of weekly weights is not significantly different between control and
      experimental lines but correlations between necropsy traits do differ, especially
      those involving the heart, kidney and tail length.

PMID- 21726330
TI  - Using creation science to demonstrate evolution 2: morphological continuity
      within Dinosauria.
AB  - Creationist literature claims that sufficient gaps in morphological continuity
      exist to classify dinosaurs into several distinct baramins ('created kinds').
      Here, I apply the baraminological method called taxon correlation to test for
      morphological continuity within and between dinosaurian taxa. The results show
      enough morphological continuity within Dinosauria to consider most dinosaurs
      genetically related, even by this creationist standard. A continuous
      morphological spectrum unites the basal members of Saurischia, Theropoda,
      Sauropodomorpha, Ornithischia, Thyreophora, Marginocephalia, and Ornithopoda with
      Nodosauridae and Pachycephalosauria and with the basal ornithodirans Silesaurus
      and Marasuchus. Morphological gaps in the known fossil record separate only seven
      groups from the rest of Dinosauria. Those groups are Therizinosauroidea +
      Oviraptorosauria + Paraves, Tazoudasaurus + Eusauropoda, Ankylosauridae,
      Stegosauria, Neoceratopsia, basal Hadrosauriformes and Hadrosauridae. Each of
      these seven groups exhibits within-group morphological continuity, indicating
      common descent for all the group's members, even according to this creationist
      standard.

PMID- 21726331
TI  - Postmating isolation and genetically variable host use in ecologically divergent
      host forms of Neochlamisus bebbianae leaf beetles.
AB  - Ecological speciation studies have more thoroughly addressed premating than
      postmating reproductive isolation. This study examines multiple postmating
      barriers between host forms of Neochlamisus bebbianae leaf beetles that
      specialize on Acer and Salix trees. We demonstrate cryptic isolation and reduced
      hybrid fitness via controlled matings of these host forms. These findings reveal
      host-associated postmating isolation, although a nonecological, 'intrinsic' basis
      for these patterns cannot be ruled out. Host preference and performance results
      among cross types further suggest sex-linked maternal effects on these traits,
      whereas family effects indicate their genetic basis and associated variation.
      Genes of major effect appear to influence these traits. Together with previous
      findings of premating isolation and adaptive differentiation in sympatry, our
      results meet many assumptions of 'speciation with gene flow' models. Here, such
      gene flow is likely asymmetric, with consequences for the dynamics of future
      ecological divergence and potential ecological speciation of these host forms.

PMID- 21726332
TI  - Marcus Wallenberg International Symposium in Comparative Reproductive Immunology,
      "Immunology at the fetal maternal interface: Basic science and clinical
      applications", July 7-8th, 2011, Linkoping University, Sweden. Editorial.

PMID- 21726333
TI  - Peri-conceptual cytokines--setting the trajectory for embryo implantation,
      pregnancy and beyond.
AB  - PROBLEM: The peri-conceptual environment influences the early embryo to impart
      long-term consequences for the fetus and neonate; however, the underlying
      mechanisms are not well defined. METHOD OF STUDY: We argue that the cytokine
      network acting in the female reproductive tract during the pre- and peri
      implantation period integrates environmental information to program the embryo
      and fine-tune the maternal immune response and endometrial remodelling to
      determine implantation success. RESULTS: As well as sex steroid hormones and male
      seminal fluid factors, female tract cytokines are influenced by agents signalling
      via the Toll-like receptors including the microbiome and a plethora of metabolic,
      chemical and other stressors. In mouse models, an altered peri-conceptual
      cytokine environment induced by cytokine deficiency, inflammatory insults or
      dysregulated seminal fluid signalling is associated with adverse effects on
      embryo development, pregnancy viability and reproductive outcome. CONCLUSION: The
      cytokine network provides a pivotal mechanism through which environmental factors
      influence both embryo development and receptivity of the uterus.

PMID- 21726334
TI  - Seminal plasma proteins: what role do they play?
AB  - PROBLEM: Semen is a heterogeneous and complex cell suspension in a protein-rich
      fluid with different functions, some of them well known, others still obscure.
      METHOD OF STUDY: This paper reviews, comparatively, our current knowledge on the
      growing field of proteomics of the SP and its relevance in relation to the in
      vivo situation, for the sake of reproductive biology, diagnostics and treatment.
      RESULTS: Ejaculated spermatozoa, primarily bathing in cauda epididymal fluid, are
      (in vitro) bulky, exposed to most, if not all, secretions from the accessory
      sexual glands. In vivo, however, not all spermatozoa are necessarily exposed to
      all secretions from these glands, because sperm cohorts are delivered in
      differential order and bathe in seminal plasma (SP) with different concentrations
      of constituents, including peptides and proteins. Proteins are relevant for sperm
      function and relate to sperm interactions with the various environments along the
      female genital tract towards the oocyte vestments. Specific peptides and proteins
      act as signals for the female immune system to modulate sperm rejection or
      tolerance, perhaps even influencing the relative intrinsic fertility of the male
      and/or couple by attaining a status of maternal tolerance towards embryo and
      placental development. CONCLUSIONS: Proteins of the seminal plasma have an ample
      panorama of action, and some appear responsible for establishing fertility.

PMID- 21726335
TI  - Endometrial receptivity and human embryo implantation.
AB  - PROBLEM: The pre-requisite of successful implantation involves an intricate
      cascade of molecular interactions which plays a crucial role in preparing
      receptive endometrium and implanting blastocyst. METHOD OF STUDY: Data are hereby
      presented for a better understanding of endometrial receptivity in women, hoping
      to provide a comprehensive picture of the process and identify new areas of basic
      and translational research in the biology of blastocyst implantation. RESULTS:
      Timely regulation of the expression of a number of complex molecules like
      hormones, cytokines and growth factors, and their crosstalk from embryonic and
      maternal endometrial side play a major role in determining the fate of the
      embryo. The molecular basis of endometrial receptivity and the mechanisms by
      which the blastocyst first adheres to the luminal epithelium and then penetrates
      into the stroma are only just beginning to be resolved. CONCLUSION: Advances in
      the development of implantation models and 'omics' technologies, particularly
      proteomics and metabolomics, are set to have a major impact on the development of
      this field.

PMID- 21726336
TI  - Regulatory T helper cells in pregnancy and their roles in systemic versus local
      immune tolerance.
AB  - PROBLEM: During pregnancy, the maternal immune system needs to adapt in order not
      to reject the semi-allogenic fetus. METHOD: In this review, we describe and
      discuss the role of regulatory T (Treg) cells in fetal tolerance. RESULTS: Treg
      cells constitute a T helper lineage that is derived from thymus (natural Treg
      cells) or is induced in the periphery (induced Treg cells). Treg cells are
      enriched at the fetal-maternal interface, showing a suppressive phenotype. In
      contrast, Treg cells are not increased in the circulation of pregnant women, and
      the suppressive capacity is similar to that in non-pregnant women. However,
      aberrations in Treg frequencies and functions, both systemically and in the
      uterus, may be involved in the complications of pregnancy. CONCLUSION: Treg cells
      seem to have distinguished roles locally versus systemically, based on their
      distribution and phenotype.

PMID- 21726337
TI  - Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations
      are enriched in human early normal pregnancy decidua: a phenotypic study of
      paired decidual and peripheral blood samples.
AB  - PROBLEM: Regulatory T cells (Treg cells), a small subset of CD4(+) T cells
      maintaining tolerance by immunosuppression, are proposed contributors to the
      survival of the fetal semiallograft. We investigated Treg cells in paired
      decidual and peripheral blood (PB) samples from healthy women in early pregnancy
      and PB samples from non-pregnant women. METHOD OF STUDY: Distribution, location,
      cytokine mRNA, and phenotype were assessed in CD4(+) CD25(+) Treg cells from
      paired samples using immunohistochemistry, immunofluorescence, flow cytometry,
      and real-time quantitative RT-PCR. RESULTS: The presence and in situ distribution
      of CD4(+) Foxp3(+) Treg cells in decidua are hereby demonstrated for the first
      time. Three Foxp3(+) cell populations, CD4(+) CD25(++) Foxp3(+), CD4(+) CD25(+)
      Foxp3(+), and CD4(+) CD25(-) Foxp3(+), were enriched locally in decidua. In
      contrast, no statistically significant difference in numbers of circulating Treg
      cells between pregnant and non-pregnant women was found. The Foxp3(+) cells
      expressed the surface molecules CD45RO, CTLA-4, CD103, Neuropilin-1, LAG-3,
      CD62L, and TGFbeta1 mRNA consistent with Treg phenotype. The population of CD4(+)
      CD25(-) Foxp3(+) cells, not described in human decidua before, was enriched 10
      fold compared with PB in paired samples. Their cytokine expression was often
      similar to Th3 profile, and the Foxp3 mRNA expression level in CD4(+) CD25(-)
      cells was stable and comparable to that of CD4(+) CD25(+) Treg cells implying
      that the majority of CD4(+) CD25(-) Foxp3(+) cells might be naive Treg cells.
      CONCLUSION: (i) There is a local enrichment of Treg cells in decidua (ii) The
      exclusive accumulation of decidual CD4(+) CD25(-) Foxp3(+) cells suggests an
      additional reservoir of Foxp3(+) naive Treg cells that can be converted to
      'classical' Treg cells in uterus.

PMID- 21726338
TI  - Reduction in miR-141 is induced by leukemia inhibitory factor and inhibits
      proliferation in choriocarcinoma cell line JEG-3.
AB  - PROBLEM: Starting from the peri-implantation period, leukemia inhibitory factor
      (LIF) is a major regulator of trophoblast functions. Micro-RNAs (miRNA) are short
      non-coding RNA sequences, which regulate expression of genes at post
      transcriptional level. The influence of LIF on miRNA expression in trophoblastic
      cells has not yet been analyzed and was focus of this investigation. METHOD OF
      STUDY: JEG-3 choriocarcinoma cells have been stimulated with LIF for 1, 2, 4, 6,
      and 24 hr. The expression of miR-9, miR-141, miR-21, miR-93, and let-7 g has been
      analyzed by real-time PCR. Subsequently, miR-141 has been silenced and over
      expressed to test its role in the proliferation of JEG-3 cells after 24 and 48
      hr. RESULTS: MiR-141 has been significantly downregulated by more than 50% after
      LIF stimulation, while miR-21 and miR-93 expression has been significantly
      upregulated. Silencing of miR-141 completely inhibited the proliferation of JEG-3
      cells, while over-expression had no effect. CONCLUSION: LIF regulates expression
      of miRNA in trophoblastic cells, which may be responsible for several functional
      effects induced by LIF.

PMID- 21726339
TI  - Innate immunity in the human endometrium and ovary.
AB  - PROBLEM: Microbial infections of the upper female genital tract perturb the
      function of the endometrium and ovary. Defense of these tissues is predominantly
      dependent on innate immunity. This review gives a perspective on innate immunity
      in the non-pregnant upper female genital tract of women. METHOD OF STUDY:
      Literature review of innate immunity in the human endometrium and ovary. RESULTS:
      The endometrium is defended against microbes by physical barriers, antimicrobial
      peptides, complement, Toll-like receptors (TLRs), and other pattern recognition
      receptors. Endometrial epithelial and stromal cells express TLRs, which sense
      pathogen-associated molecular patterns (PAMPs), leading to an inflammatory
      response with the influx of neutrophils and macrophages. Innate immunity in the
      endometrium is regulated by steroids, eicosanoids, and cytokines. Granulosa cells
      also express TLRs and respond to PAMPs. CONCLUSION: Pattern recognition receptors
      have roles in endometrial and ovarian inflammation, and innate immunity is
      central to the defense of the endometrium against pathogens.

PMID- 21726340
TI  - Epigenetics--the key to understand immune responses in health and disease.
AB  - PROBLEM: Development of alternative CD4(+) T cells provides flexibility to the
      immune system. This is crucial for the initiation of appropriate effector
      mechanisms to protect against various pathogens such as bacteria, viruses,
      tumors, and parasites. METHOD OF STUDY: Review of research on the epigenetic
      regulation of T-cell subsets. RESULTS: Studies of the epigenetic modulation of T
      cell subset function/dysfunction during the past years have increased our
      understanding of how the alternative effector populations arise and how their
      identity is maintained during clonal expansion. CONCLUSIONS: The recent advances
      in epigenetic research within the field of immunology have also raised questions
      on how immunology is regulated during pregnancy and early life and how epigenetic
      regulation of the immune system during prenatal development is related to
      diseases later in life such as autoimmunity and allergy.

PMID- 21726341
TI  - Childhood immune maturation and allergy development: regulation by maternal
      immunity and microbial exposure.
AB  - PROBLEM: The increasing allergy prevalence in affluent countries may be caused by
      reduced microbial stimulation, resulting in an abnormal post-natal immune
      maturation. Most studies investigating the underlying mechanisms have focused on
      post-natal microbial exposure. Also, the maternal microbial environment during
      pregnancy may program the immune development of the child, however. METHOD OF
      STUDY: This review focuses on how maternal immunity and microbial exposures
      regulate childhood immune and allergy development. RESULTS: Prenatal
      environmental exposures may alter gene expression via epigenetic mechanisms,
      aiming to induce physiological adaptations to the anticipated post-natal
      environment, but potentially also increasing disease susceptibility in the
      offspring. Although the importance of fetal programming mostly has been studied
      in cardiovascular and metabolic disease, this hypothesis is also very attractive
      in the context of environmentally influenced immune-mediated diseases.
      CONCLUSION: Efficacious preventive measures, required to combat the allergy
      epidemic, may be identified by determining how the immune interaction between
      mother and child is influenced by microbial factors.

PMID- 21726342
TI  - Long-term consequences of non-optimal birth characteristics.
AB  - PROBLEM: The intrauterine milieu, gestational length as well as size at birth
      have a profound impact on the individual's mental, physical health and
      development both in childhood as well as in adult life. METHOD OF STUDY: This
      paper reviews the associations between preterm birth and restricted fetal growth
      with neuro-developmental sequelae, including increased symptoms of psychiatric
      disorder in childhood and early adulthood. There is also evidence that physical
      morbidity such as the metabolic syndrome is more common in adult life. In
      addition, preterm birth and restricted fetal growth have been shown to be related
      to respiratory disease, infectious disease, and even malignancy. Morbidity,
      mental and physical as well as personality/intellectual traits hugely impact on
      family planning and reproductive performance in adults. As restricted fetal
      growth may alter organ structure and functions, it is likely to also influence
      subsequent fertility and/or reproductive health. RESULTS: Individuals with non
      optimal birth characteristics appears to have a reduction in childbearing and a
      deviant reproduction pattern compared to controls. CONCLUSION: Future studies
      with sophisticated models for measuring the most vulnerable period of birth for
      children who have a low birth weight or who are at risk for being born preterm
      are needed to be able to explore the underlying biological mechanisms and also to
      plan for prevention as well as for interventions during pregnancy.

PMID- 21726343
TI  - Uterine Regulatory T cells, IL-10 and hypertension.
AB  - PROBLEM: Regulatory T cells (T(reg) ) are a vital immune cellular population at
      the maternal-fetal interface. They are likely to aid in immune tolerance by
      dampening the harmful effects of other immune cellular populations through cell
      cell-mediated interactions as well as by producing IL-10 and TGF-beta. In
      addition to the anti-inflammatory properties, IL-10 has emerged as an important
      vascular cytokine choreographing endovascular interactions and angiogenesis and
      regulates hypertension. METHOD OF STUDY: Review of innovative concepts to
      understand the temporal role of T(regs) in both mouse and human pregnancy,
      particularly whether uterine T(reg) play a potential role in regulating vascular
      homeostasis and blood flow during pregnancy. RESULTS: T(reg) guard immune
      tolerance, getting cytotoxically activated under certain conditions, leading to
      adverse pregnancy outcome. CONCLUSION: Despite increasing evidence of T(reg)
      tissue-specific expansion and functional plasticity, their role in vascular
      activity, pre-eclampsia or gestational diabetes is obscure and needs closer
      investigation to delineate its role later during pregnancy.

PMID- 21726344
TI  - Anti-HY responses in pregnancy disorders.
AB  - PROBLEM: Cellular and humoral immune responses against male-specific minor
      histocompatibility (HY) antigens are important in the pathogenesis of graft
      versus-host reactions and can be detected in women who have previously given
      birth to a boy. However, the importance of these responses for pregnancy outcome
      is unclear. METHOD OF STUDY: Review of the current knowledge about the impact of
      anti-HY immunity on pregnancy outcome in terms of risk of miscarriage, placental
      abruption and low birth weight. RESULTS: Women with secondary recurrent
      miscarriage (RM) more often have given birth to a boy compared with a girl prior
      to a series of miscarriages (P<0.0001) and a firstborn boy seems significantly to
      reduce the chance of a subsequent live in these patients (P=0.0003). Human
      leukocyte antigen (HLA) class II alleles known to restrict CD4 T-cell-mediated
      anti-HY responses were investigated among 358 patients with secondary RM and 203
      of their children born prior to the miscarriages. The chance of a subsequent live
      birth in secondary RM patients with firstborn boys compared with firstborn girls
      was significantly lower in women with HY-restricting HLA class II alleles [OR:
      0.17 (0.1-0.4), P=0.0001]. In patients without these alleles, the chance of live
      birth was similar in those with firstborn boys and girls, respectively. In early
      pregnancy, both antibodies against HLA and HY antigens were found with increased
      prevalence in secondary patients with RM and in particular in those with a
      firstborn boy compared with controls (P=0.005). The presence of these antibodies
      was associated with a low subsequent live birth rate, and the presence of HY
      antibodies was associated with a low male/female ratio (12% boys versus 88%
      girls) in subsequent live births (P=0.03). Register-based population studies
      suggested that births of boys also are associated with subsequent adverse
      obstetric outcomes also in the background population. CONCLUSION: Findings
      strongly indicate that aberrant maternal immune reactions against fetal HY
      antigens playing a role in secondary RM and other pregnancy complications. We
      propose pathogenetic pathways for these conditions that in our view best explain
      the findings.

PMID- 21726345
TI  - Immunological aspects of endometriosis: an update.
AB  - PROBLEM: Endometriosis is a very complex disease that profoundly affects the
      quality of life of many women. METHOD OF STUDY: A review of the relationships
      between the female immune system and the occurrence and development of
      endometriosis. RESULTS: Function and dysfunction of the female immune system
      plays important roles in the initiation and progression of the disease and its
      relation to infertility and cancer. CONCLUSIONS: Owing to obvious associations
      between endometriosis and the immune system, future treatment strategies might be
      based on immunological concepts and methods.

PMID- 21726347
TI  - Age and associated fibrocystic changes are prognostically significant in patients
      with small node-negative (T1a,bN0) invasive breast cancer.
AB  - Some patients with small (<=1.0 cm) node-negative (T1a,bN0) invasive breast
      cancer (IBC) who undergo only local therapy experience recurrences. There is
      limited information on prognostic factors in these patients. We sought to
      identify prognostic factors associated with disease-free survival (DFS) and
      overall survival (OS) in patients with T1a,bN0 IBC. Histologic sections from 273
      T1a,bN0 IBC patients treated at M. D. Anderson Cancer Center (MDACC) between 1980
      and 1999 were reviewed. Microscopic tumor size; multifocality; histologic type,
      grade of tumor; presence, type, grade of associated ductal carcinoma in situ
      (DCIS); presence of fibrocystic changes (FCC) with/without atypia; and
      lymphovascular invasion were identified. The Kaplan-Meier method was used to
      evaluate DFS and OS. Median patient age was 58 years, median follow-up period was
      10.8 years, and median tumor size was 0.8 cm. Multifocal disease was identified
      in 26% of cases. At 10 years, the DFS and OS rates were 91% and 88%,
      respectively. Twenty-one percent of patients had extensive (>50%), and 30% had
      grade 3 DCIS. Nonproliferative FCC and proliferative FCC with/without atypia were
      present in 80%, 36%, and 38% of patients, respectively. In univariate analysis,
      age at diagnosis (p < 0.0001), grade (p = 0.015), and percent (p = 0.046) of DCIS
      were significantly associated with DFS; presence of FCC was associated with
      longer DFS and OS. In multivariable models, age and presence of FCC remained
      significantly associated with survival. Age at diagnosis and associated FCC are
      significant factors in predicting recurrence in patients with T1a,bN0 IBC.
      Adjuvant systemic therapy should be discussed with and considered for young
      patients with T1a,bN0 IBC.

PMID- 21726348
TI  - Capecitabine (and 5 fluorouracil) cardiotoxicity. Metabolic considerations.

PMID- 21726349
TI  - Primary phyllodes tumor of the axilla: DCE-MRI findings with 1.5T breast
      dedicated system and pathological correlation.

PMID- 21726350
TI  - Surviving metastatic breast cancer for 18 years: a case report and review of the
      literature.
AB  - We report a case of a 93-year-old woman who was diagnosed with estrogen receptor
      (ER)-positive, progesterone receptor-positive, T2N0M0 (stage I) breast cancer
      (BC) at the age of 45. Twenty-two years later, she was diagnosed with metastatic
      lesions to the lungs consistent with the breast primary. Her disease was stable
      on tamoxifen, anastrozole, and exemestane for 14 years. Subsequently, she was
      found to have metastatic lesions to thoracic spine as well as progressively
      increasing bilateral pleural effusions. At that time, she was deemed not to be a
      good candidate for chemotherapy and therapy was changed to fulvestrant. Two years
      later (38 years after initial diagnosis of BC), she was diagnosed with new
      metastatic liver lesions; although her pulmonary and bone metastases remained
      stable. Therefore, she was started on palliative chemotherapy with single-agent
      capecitabine. The treatment was discontinued after the second cycle upon the
      patient's request owing to grade 2 hand and foot syndrome. She expired 2 years
      later after fighting BC for four decades. She survived for 18 years after the
      diagnosis of metastatic breast cancer (MBC) while maintaining a good quality of
      life. To the authors' knowledge, this is the first reported case in the
      literature with the longest overall survival in a patient with MBC. We provide a
      detailed clinical analysis in conjunction with a brief literature review.

PMID- 21726351
TI  - Post-transplant lymphoproliferative disorder at the site of recurrent breast
      abscesses.

PMID- 21726352
TI  - Characterizing the behavior of children emerging with delirium from general
      anesthesia.
AB  - BACKGROUND: Emergence delirium (ED) frequently occurs in young children awakening
      from general anesthesia (GA). To date, research is limited by scales that are
      unable to discriminate the condition from other forms of agitation. AIM: The
      primary aim of this study was to determine the core behaviors of ED that
      discriminate the condition from pain and tantrum in young children and to cluster
      these behaviors according to the DSM-IV/V core diagnostic criteria and associated
      behaviors of delirium. METHOD: Children aged 18 months to 6 years (n=198) were
      observed upon awakening from GA following surgical or nonsurgical procedures to
      determine which behaviors categorize ED. Behaviors were recorded via a structured
      behavioral observation. Clinical opinion was sought to determine whether the
      child presented ED, pain, or tantrum. RESULTS: A chi-square analysis revealed
      children with ED were significantly more likely to display activity,
      nonpurposefulness, eyes averted, stared or closed, no language, and
      nonresponsivity. These behaviors were not significantly associated with pain or
      tantrum. A logistic regression showed eyes averted or stared and
      nonpurposefulness were significant predictors of ED, while no language and
      activity were not significant predictors of ED. CONCLUSIONS: Children with ED are
      significantly more likely to display nonpurposefulness, eyes averted, stared or
      closed, and nonresponsivity. These behaviors were not significantly associated
      with pain or tantrum and are believed to reflect the DSM-IV/V diagnostic criteria
      for delirium. Associated behaviors of ED identified by this research are
      irrelevant language, activity, and vocalization.

PMID- 21726353
TI  - Is microsporidial keratitis a seasonal infection in India?
AB  - Microsporidia are emerging ocular pathogens. In this study, we describe the
      seasonal trends of microsporidial keratitis. The incidence of microsporidial
      keratitis is increasing in India, with a seasonal trend towards disease onset
      during the monsoon.

PMID- 21726354
TI  - Low-dose hydrocortisone treatment for patients with septic shock: a pilot study
      comparing 3days with 7days.
AB  - BACKGROUND AND OBJECTIVE: Although there is controversy regarding the benefit of
      low-dose corticosteroid therapy in patients with septic shock, the Surviving
      Sepsis Campaign has advocated that low-dose intravenous hydrocortisone be used to
      treat adult septic shock patients. This study investigated the effect of the
      duration of a stress dose of hydrocortisone on survival of septic shock patients
      with relative adrenal insufficiency. METHODS: One hundred and thirty consecutive
      patients who met the American College of Chest Physicians/Society of Critical
      Care Medicine criteria for septic shock were included in the study. An additional
      inclusion criterion was vasopressor support after fluid resuscitation. The
      primary end-point was 28-day mortality, and the secondary end-points were shock
      reversal and mortality in the intensive care unit and hospital. All eligible
      patients were prospectively randomized to receive hydrocortisone treatment for 3
      or 7days. Hydrocortisone treatment was started at a dose of 50mg every 6h.
      RESULTS: Baseline data at recruitment did not differ between the two groups.
      After 28days, mortality did not differ between the 3- and 7-day treatment groups
      (33.8% vs 36.9%, P=0.629). Mortality rates in the intensive care unit and
      hospital did not differ significantly between the two groups. The median time to
      withdrawal of vasopressor therapy was 5.0days in the 3-day treatment group and
      6.4days in the 7-day treatment group (P=0.102). CONCLUSIONS: This pilot study
      showed that in patients with septic shock and relative adrenal insufficiency, 28
      day mortality did not differ between those treated with low-dose hydrocortisone
      for 3 or 7days.

PMID- 21726355
TI  - A novel CB receptor GPR55 and its ligands are involved in regulation of gut
      movement in rodents.
AB  - BACKGROUND: This study was to investigate the effects of the novel cannabinoid
      receptor - G protein-coupled receptor 55 (GPR55) - and its ligands O-1602 and
      cannabidiol (CBD) on gastrointestinal (GI) motility in rodents. METHODS:
      Lipopolysaccharide (LPS) was used in vivo to produce the model of septic ileus.
      The intestinal motility was measured by recording myoelectrical activity of
      jejunum in rats, and by measuring GI transit with a charcoal marker in mice, in
      presence of O-1602 or CBD. Inflammatory response was assessed serologically and
      histologically. The expression and distribution of GPR55 in the different parts
      of rat intestine were investigated by real-time PCR and immunohistochemistry. In
      vitro, the effects of the drugs on the GI movement were investigated by measuring
      the contraction of the intestinal muscle strips in organ bath, and the
      intracellular responses of the muscle cells with microelectrode technique. KEY
      RESULTS: G protein-coupled receptor 55 was expressed in different parts of rat
      intestine. Lipopolysaccharide significantly inhibited the intestinal motility,
      increased inflammatory cytokines and GPR55 expression. Pretreatment with CBD
      normalized LPS-induced hypomotility and improved the inflammatory responses
      serologically and histologically. Both O-1602 and CBD counteracted LPS-induced
      disturbances of the gut contraction, but had no effect on the membrane potential
      of the muscle cells, while cannabinoid type 1 receptor antagonist AM251 and
      cannabinoid type 2 receptor antagonist AM630 increased the potential. CONCLUSIONS
      & INFERENCES: G protein-coupled receptor 55 existed throughout the whole
      intestine of rats. O-1602 or CBD selectively normalized the motility
      disturbances. Possible mechanisms involved systemic anti-inflammation and the
      regulation of myoelectrical activity of the intestine.

PMID- 21726356
TI  - Evaluate symptomatic therapy in MS: can clinical trials be fine-tuned?

PMID- 21726357
TI  - Repeated infusions of VWF/FVIII concentrate: impact of VWF:FVIII ratio on FVIII
      trough and peak levels in a rabbit model.
AB  - The ratio of von Willebrand factor (VWF) to FVIII differs among available
      VWF/FVIII concentrates. Repeated infusions of concentrates with a low VWF:FVIII
      ratio may expose patients with von Willebrand disease to supranormal FVIII
      levels. The aim of this study was to determine the effects of repeated infusions
      with two VWF/FVIII concentrates differing in VWF:FVIII ratio on attained FVIII
      trough and peak levels as well as other pharmacokinetic parameters. Rabbits were
      randomized to receive multiple 150 IU kg-1 VWF:RCo infusions at 4 h intervals
      with VWF/FVIII concentrates of a high (Haemate(r) P/Humate-P(r)) or low
      (Wilate(r)) VWF:FVIII ratio. Trough plasma FVIII and VWF levels were measured
      after each infusion. Pharmacokinetic analysis was performed using samples
      collected frequently after infusion. Mean FVIII trough level after the first
      Wilate infusion was 50.6 IU dL-1 with a 95% confidence interval (CI) of 43.1-58.2
      IU dL-1, compared with 31.8 IU dL-1 (CI, 24.4-39.1 IU dL-1) for Haemate P
      (P<0.001). Trough levels progressively increased over the 24 h treatment period
      in both groups. After the final infusion, mean trough FVIII remained
      significantly higher (P = 0.002) in recipients of Wilate. Mean peak FVIII
      concentration after infusion was 67% higher in the Wilate group (167 vs. 100 IU
      dL-1 , respectively; P = 0.002). Mean cumulative exposure to FVIII, as measured
      by area under the curve, was 84% greater in Wilate-treated animals. Half-life did
      not differ between the two concentrates. Animal model data suggest that exposure
      to elevated FVIII levels can be reduced through use of VWF/FVIII concentrates
      with higher VWF:FVIII ratios.

PMID- 21726358
TI  - Influence of class I and II HLA alleles on inhibitor development in severe
      haemophilia A patients from the south of Brazil.
AB  - Congenital haemophilia A is a chromosome-linked recessive disorder caused by the
      deficiency or reduction of factor VIII (FVIII) pro-coagulant activity. During
      treatment, some patients develop alloantibodies (FVIII inhibitors) that
      neutralize the action of exogenously administered FVIII. Currently, the presence
      of these inhibitors is the most serious adverse event found in replacement
      therapy. Some studies have suggested that genetic factors influence the
      development of the FVIII coagulation inhibitors. To identify the class I and II
      alleles that may be influencing the formation of inhibitors in severe haemophilic
      patients. Genotyping of the class I (HLA-A, -B and -C) and class II (HLA-DRB1, 
      DQA1 and -DQB1) alleles of 122 patients with severe haemophilia A, including 36
      who had developed antibodies to factor VIII, was performed. After the comparison
      of the group without inhibitors and the group with inhibitors, HLA-C*16 [Odds
      ratio (OR) = 7.73; P = 0.0092] and HLA-DRB1*14 (OR = 4.52; P = 0.0174) were found
      to be positively associated with the formation of the inhibitors. These results
      confirm that HLA alleles are involved in inhibitor production and could be used
      as a tool for recognition of groups at high risk of possible inhibitor
      development in Southern Brazilian haemophilic patients.

PMID- 21726359
TI  - Reducing interrater variability and improving health care: a meta-analytical
      review.
AB  - OBJECTIVES: In the scientific literature about reliability, the main approach to
      increasing reliability seems to involve increasing the number of observers and
      improving the instrument used. Other aspects for improving reliability - like the
      training of raters - seem to receive less notice. It is worth asking whether this
      technical approach could be complemented by training the user of the instrument.
      A systematic meta-analytical review of the research literature was performed to
      answer this question and examine the effectiveness of planned interventions for
      improving interrater reliability of health care professionals. METHOD: The
      databases of PubMed (MEDLINE), Embase, Omega and PsycINFO were searched. The
      inclusion criteria were met by 57 studies. Details extracted from the studies
      included the study design, the number of observers and the number of observed
      cases, the intervention, the type of instrument (whether or not it was highly
      technical), and statistical information about the agreement before and after the
      intervention. Interventions were categorized into three groups: training of
      professionals, improving the diagnostic instrument and a combination of training
      and improving the instrument. A meta-analysis was performed by means of linear
      regression. RESULTS: The interventions were arranged according to their
      effectiveness in improving the diagnostic instrument (mean change: beta = 0.13),
      training combined with improving the instrument (mean change: beta = 0.10) and
      training (mean change: beta = 0.09). CONCLUSION: On average, although all types
      of interventions are effective, improving the diagnostic instrument seems to be
      the most effective. Especially when highly technical instruments were concerned,
      improvement proved to be very effective (beta = 0.52). Because instrumental
      variables constitute a major source of error, improving the instrument is an
      important approach. However, this review offers solid arguments that can
      complement the literature and practice, with a focus on training the user of the
      instrument.

PMID- 21726360
TI  - Selective inhibition of Erwinia amylovora by the herbicidally active germination
      arrest factor (GAF) produced by Pseudomonas bacteria.
AB  - AIMS:  The germination-arrest factor (GAF) produced by Pseudomonas fluorescens
      WH6, and identified as 4-formylaminooxyvinylglycine, specifically inhibits the
      germination of a wide range of grassy weeds. This study was undertaken to
      determine whether GAF has antimicrobial activity in addition to its inhibitory
      effects on grass seed germination. METHODS AND RESULTS: Culture filtrate from Ps.
      fluorescens WH6 had little or no effect on 17 species of bacteria grown in Petri
      dish lawns, but the in vitro growth of Erwinia amylovora, the causal agent of the
      disease of orchard crops known as fire blight, was strongly inhibited by the
      filtrate. The anti-Erwinia activity of WH6 culture filtrate was shown to be due
      to its GAF content, and a commercially available oxyvinylglycine, 4
      aminoethoxyvinylglycine (AVG), exhibited anti-Erwinia activity similar to that of
      GAF. The effects of GAF on Erwinia were reversed by particular amino acids.
      CONCLUSIONS: The biological properties of GAF include a rather specific
      antimicrobial activity against Erw. amylovora. This may be a general property of
      oxyvinylglycines as AVG exhibited similar activity. The ability of particular
      amino acids to reverse GAF inhibition is consistent with a potential effect of
      this compound on the activity of aminotransferases. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The results presented here demonstrate a novel antimicrobial activity
      of oxyvinylglycines and suggest that GAF and/or GAF-producing bacteria may have
      potential for the control of fire blight.

PMID- 21726361
TI  - Improved pectinase production in Penicillium griseoroseum recombinant strains.
AB  - AIMS: To obtain recombinant strains of Penicillium griseoroseum that produce high
      levels of pectin lyase (PL) and polygalacturonase (PG) simultaneously. METHODS
      AND RESULTS: A strain with high production of PL was transformed with the plasmid
      pAN52pgg2, containing the gene encoding PG of P. griseoroseum, under control of
      the gpd promoter gene from Aspergillus nidulans. Southern blot analysis
      demonstrated that all strain had at least one copy of pAN52pgg2 integrated into
      the genome. The recombinant strain P. griseoroseum T20 produced levels of PL and
      PG that were 266- and 27-fold greater, respectively, than the wild-type strain.
      Furthermore, the extracellular protein profile of recombinant T20 showed two
      protein bands of c. 36 and 38 kDa, associated with PL and PG, respectively.
      CONCLUSIONS: This recombinant strain T20 produces PL and PG using carbon sources
      of low costs, and an enzyme preparation that is free of cellulolytic and
      proteolytic activities. SIGNIFICANCE AND IMPACT OF THE STUDY: PL and PG play an
      important role in the degradation of pectin. Owing to their use in the juice and
      wines industries, there is a growing interest in the inexpensive production of
      these enzymes. This work describes an efficient system of protein expression and
      secretion using the fungus P. griseoroseum.

PMID- 21726362
TI  - Do treatment preferences for patients with angina change? An 18-month follow-up
      study.
AB  - OBJECTIVES: To assess whether preferences for patients with angina changed at 18
      month follow-up using the Patient Preferences Questionnaire for Angina treatment
      (PPQA). BACKGROUND: Evidence suggests that patients want information about
      treatment options. Reliable measurement of patient preferences for treatment is
      important for empowering patients. DESIGN: Postal self-administered questionnaire
      survey at baseline and follow-up. The preference questionnaire comprised 18 items
      about the main treatments for angina: medication, angioplasty and coronary artery
      bypass grafting (CABG). SETTING AND PARTICIPANTS: Patients with diagnosed angina
      from seven participating general practices across England. The sample comprised
      222 patients with angina who responded to both baseline and follow-up treatment
      preference questionnaires. RESULTS: Most patients' condition and preferences
      scores for treatment remained stable over 18 months. An exception was angioplasty
      preference scores, which indicated more negative attitudes towards this procedure
      over time. People aged over 75 years least preferred angioplasty. There were no
      associations between any changes in condition and changes in preferences.
      However, within-subject agreement could vary by +/- 5 to 7 points between
      baseline and follow-up, with stability apparently worst for the medication and
      best for surgery sub-scales, raising the question of what represents reasonable
      stability. CONCLUSION: These results suggest preferences are relatively stable,
      even where there are changes in health, and provide further evidence of the
      utility (in particular, reliability) of the PPQA. However, this stability in
      scores did mask some movement in scale scores and in patients' first-ranked
      treatment choices, showing changing preferences largely from angioplasty to CABG
      and vice versa, indicating the complexity of preferences.

PMID- 21726363
TI  - What Australian women want and when they want it: cervical screening testing
      preferences, decision-making styles and information needs.
AB  - BACKGROUND: New testing technologies and human papillomavirus (HPV) vaccines have
      recently brought changes to cervical cancer screening. In 2006, the Australian
      government also changed the protocol for managing abnormal Pap smears. Australian
      women's attitudes and preferences to these changes are largely unknown.
      Quantitative data on information needs and community attitudes to informed
      decision making in screening in Australia are also limited. OBJECTIVE: This
      national study measures women's preferences for testing and management of
      abnormal screening results, preferred decision-making styles and information
      needs for cervical cancer screening. DESIGN: A randomly selected sample of
      Australian women aged 18-70 participated in a structured telephone questionnaire,
      exploring testing preferences, information and decision-making needs. RESULTS: A
      total of 1279, of 1571 eligible women, participated in the study with an overall
      response rate of 81.4%. Half of the women (n = 637) preferred having their Pap
      smears at least annually, and 85% wanted concurrent HPV testing. A large
      proportion of women preferred to be involved in decision making for both routine
      Pap smears (87%) and follow-up for abnormal results (89%). The majority of women
      wanted information on screening risks (70%) and benefits (77%); of these 81 (85%)
      wanted this information before screening. However, 63% of women only wanted
      information about follow-up examinations if they had an abnormal Pap test result.
      CONCLUSION: Australian women want to be involved in decision making for cervical
      cancer screening and require information on the risks and benefits of Pap testing
      prior to undergoing any screening.

PMID- 21726364
TI  - Pseudomonas syringae pv. phaseolicola: from 'has bean' to supermodel.
AB  - Pseudomonas syringae pv. phaseolicola causes halo blight of the common bean,
      Phaseolus vulgaris, worldwide and remains difficult to control. Races of the
      pathogen cause either disease symptoms or a resistant hypersensitive response on
      a series of differentially reacting bean cultivars. The molecular genetics of the
      interaction between P. syringae pv. phaseolicola and bean, and the evolution of
      bacterial virulence, have been investigated in depth and this research has led to
      important discoveries in the field of plant-microbe interactions. In this review,
      we discuss several of the areas of study that chart the rise of P. syringae pv.
      phaseolicola from a common pathogen of bean plants to a molecular plant-pathogen
      supermodel bacterium. TAXONOMY: Bacteria; Proteobacteria, gamma subdivision;
      order Pseudomonadales; family Pseudomonadaceae; genus Pseudomonas; species
      Pseudomonas syringae; Genomospecies 2; pathogenic variety phaseolicola.
      MICROBIOLOGICAL PROPERTIES: Gram-negative, aerobic, motile, rod-shaped, 1.5 um
      long, 0.7-1.2 um in diameter, at least one polar flagellum, optimal temperatures
      for growth of 25-30 degrees C, oxidase negative, arginine dihydrolase negative,
      levan positive and elicits the hypersensitive response on tobacco. HOST RANGE:
      Major bacterial disease of common bean (Phaseolus vulgaris) in temperate regions
      and above medium altitudes in the tropics. Natural infections have been recorded
      on several other legume species, including all members of the tribe Phaseoleae
      with the exception of Desmodium spp. and Pisum sativum. DISEASE SYMPTOMS: Water
      soaked lesions on leaves, pods, stems or petioles, that quickly develop greenish
      yellow haloes on leaves at temperatures of less than 23 degrees C. Infected seeds
      may be symptomless, or have wrinkled or buttery-yellow patches on the seed coat.
      Seedling infection is recognized by general chlorosis, stunting and distortion of
      growth. EPIDEMIOLOGY: Seed borne and disseminated from exudation by water-splash
      and wind occurring during rainfall. Bacteria invade through wounds and natural
      openings (notably stomata). Weedy and cultivated alternative hosts may also
      harbour the bacterium. DISEASE CONTROL: Some measure of control is achieved with
      copper formulations and streptomycin. Pathogen-free seed and resistant cultivars
      are recommended. USEFUL WEBSITES: Pseudomonas-plant interaction
      http://www.pseudomonas-syringae.org/; PseudoDB http://xbase.bham.ac.uk/pseudodb/;
      Plant Associated and Environmental Microbes Database (PAMDB)
      http://genome.ppws.vt.edu/cgi-bin/MLST/home.pl; PseudoMLSA Database
      http://www.uib.es/microbiologiaBD/Welcome.html.

PMID- 21726365
TI  - Pantoea stewartii subsp. stewartii: lessons learned from a xylem-dwelling
      pathogen of sweet corn.
AB  - Pantoea stewartii subsp. stewartii is a Gram-negative enteric bacterium that
      primarily infects sweet corn. Studies of this bacterium have provided useful
      insight into how xylem-dwelling bacteria establish themselves and incite disease
      in their hosts. Pantoea stewartii subsp. stewartii is a remarkable bacterial
      system for laboratory studies because of its relative ease of propagation and
      genetic manipulation, and the fact that it appears to employ a minimal number of
      pathogenicity mechanisms. In addition, P. stewartii subsp. stewartii produces
      copious amounts of its quorum sensing (QS) signal, acyl-homoserine lactone (AHL),
      making it an excellent organism for studying QS-controlled gene regulation in a
      plant-pathogenic bacterium. In fact, P. stewartii subsp. stewartii has become the
      microbial paradigm for QS control of gene expression by both repression and
      activation via a QS regulator that binds DNA in the absence and dissociates in
      the presence of the signal ligand. Moreover, P. stewartii subsp. stewartii is a
      member of the Enterobacteriaceae, and lessons learned from its interaction with
      plants may be extrapolated to other plant-associated enterics, such as Erwinia,
      Dickeya and Pectobacterium spp., or enteric human pathogens associated with
      plants, such as Escherichia coli and Salmonella spp. TAXONOMY: Bacteria;
      Gammaproteobacteria; family Enterobacteriaceae; genus Pantoea; species stewartii
      (Mergaert et al., 1993). MICROBIOLOGICAL PROPERTIES: Gram-negative, motile,
      yellow pigmented, mucoid, facultative anaerobe. HOST RANGE: Pantoea stewartii
      subsp. stewartii (Smith, 1898) Dye causes Stewart's wilt of corn (Zea mays).
      Early-maturing sweet corn varieties and some elite inbred maize lines are
      particularly susceptible. DISEASE SYMPTOMS: There are two major phases of
      Stewart's wilt disease: (i) wilt and (ii) leaf blight. The wilt phase occurs when
      young seedlings are infected with P. stewartii subsp. stewartii (Fig. 1A). Water
      soaked lesions first appear on the young expanding leaves and, later, seedlings
      may become severely wilted (Fig. 1B). The plants usually die when infected at the
      seedling stage. The leaf blight phase occurs when mature plants are infected
      (Fig. 1C). The bacteria enter the xylem and cause long linear yellow-grey lesions
      with a wavy margin that run parallel to the leaf veins. These lesions later turn
      necrotic and dark in colour. The leaf blight phase is most apparent after
      tasselling and does not generally cause death of the plant. In addition, the
      bacteria can sometimes break out of the xylem and cause pith rot in mature sweet
      corn plants. In resistant varieties, lesions are usually limited to only a few
      centimetres depending on the level of resistance of the particular hybrid
      (Claflin, 2000; Pataky, 2003). USEFUL WEBSITES:
      http://www.apsnet.org/publications/apsnetfeatures/Pages/StewartsWilt.aspx.

PMID- 21726366
TI  - Garlic virus X 11-kDa protein granules move within the cytoplasm and traffic a
      host protein normally found in the nucleolus.
AB  - The subcellular localization of the 11-kDa protein (p11) encoded by ORF3 of
      Garlic virus X (GarVX; genus Allexivirus, family Alphaflexiviridae) was examined
      by confocal microscopy. Granules with intense fluorescence were visible on the
      endoplasmic reticulum when p11 fused with green or red fluorescent protein (GFP
      or RFP) was expressed in epidermal cells of Nicotiana benthamiana. Moreover, the
      p11-RFP granules moved in the cytoplasm, along the cell periphery and through the
      cell membranes to adjacent cells. A 17-kDa protein (p17) of garlic interacting
      with p11 was identified by yeast two-hybridization and bimolecular fluorescence
      complementation assay. When p17 fused to GFP was expressed in epidermal cells of
      N. benthamiana, it localized to the nucleolus. However, in the presence of GarVX
      p11, the distribution of p17 changed to that of p11, but did not appear to affect
      the pattern of movement of p11.

PMID- 21726367
TI  - RNAi-mediated resistance to Cassava brown streak Uganda virus in transgenic
      cassava.
AB  - Cassava brown streak disease (CBSD), caused by Cassava brown streak Uganda virus
      (CBSUV) and Cassava brown streak virus (CBSV), is of new epidemic importance to
      cassava (Manihot esculenta Crantz) production in East Africa, and an emerging
      threat to the crop in Central and West Africa. This study demonstrates that at
      least one of these two ipomoviruses, CBSUV, can be efficiently controlled using
      RNA interference (RNAi) technology in cassava. An RNAi construct targeting the
      near full-length coat protein (FL-CP) of CBSUV was expressed constitutively as a
      hairpin construct in cassava. Transgenic cassava lines expressing small
      interfering RNAs (siRNAs) against this sequence showed 100% resistance to CBSUV
      across replicated graft inoculation experiments. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) analysis showed the presence of CBSUV in leaves and some
      tuberous roots from challenged controls, but not in the same tissues from
      transgenic plants. This is the first demonstration of RNAi-mediated resistance to
      the ipomovirus CBSUV in cassava.

PMID- 21726368
TI  - The SLT2 mitogen-activated protein kinase-mediated signalling pathway governs
      conidiation, morphogenesis, fungal virulence and production of toxin and melanin
      in the tangerine pathotype of Alternaria alternata.
AB  - Fungi respond and adapt to different environmental stimuli via signal
      transduction systems. We determined the function of a yeast SLT2 mitogen
      activated protein (MAP) kinase homologue (AaSLT2) in Alternaria alternata, the
      fungal pathogen of citrus. Analysis of the loss-of-function mutant indicated that
      AaSLT2 is required for the production of a host-selective toxin, and is crucial
      for fungal pathogenicity. Moreover, the A. alternata slt2 mutants displayed
      hypersensitivity to cell wall-degrading enzymes and chemicals such as Calcofluor
      white and Congo red. This implicates an important role of AaSLT2 in the
      maintenance of cell wall integrity in A. alternata. The A. alternata slt2 mutants
      were also hypersensitive to a heteroaromatic compound, 2-chloro-5
      hydroxypyridine, and a plant growth regulator, 2,3,5-triiodobenzoic acid.
      Developmentally, the AaSLT2 gene product was shown to be critical for conidial
      formation and hyphal elongation. Compared with the wild-type, the mutants
      produced fewer but slightly larger conidia with less transverse septae. The
      mutants also accumulated lower levels of melanin and chitin. Unlike the wild-type
      progenitor, the A. alternata slt2 mutants produced globose, swollen hyphae that
      did not elongate in a straight radial direction. All defective phenotypes in the
      mutant were restored by transformation and expression of a wild-type copy of
      AaSLT2 under the control of its endogenous promoter. This study highlights an
      important role of the AaSLT2 MAP kinase-mediated signalling pathway, regulating
      diverse physiological, developmental and pathological functions, in the tangerine
      pathotype of A. alternata.

PMID- 21726369
TI  - Invertases involved in the development of the parasitic plant Phelipanche ramosa:
      characterization of the dominant soluble acid isoform, PrSAI1.
AB  - Phelipanche ramosa L. parasitizes major crops, acting as a competitive sink for
      host photoassimilates, especially sucrose. An understanding of the mechanisms of
      sucrose utilization in parasites is an important step in the development of new
      control methods. Therefore, in this study, we characterized the invertase gene
      family in P. ramosa and analysed its involvement in plant development. Invertase
      encoded cDNAs were isolated using degenerate primers corresponding to highly
      conserved regions of invertases. In addition to enzyme assays, gene expression
      was analysed using real-time quantitative reverse transcriptase-polymerase chain
      reaction during overall plant development. The dominant isoform was purified and
      sequenced using electrospray ionization-liquid chromatography-tandem mass
      spectrometry (ESI-LC-MS/MS). Five invertase-encoded cDNAs were thus
      characterized, including PrSai1 which encodes a soluble acid invertase (SAI). Of
      the five invertases, PrSai1 transcripts and SAI activity were dominant in growing
      organs. The most active invertase corresponded to the PrSai1 gene product. The
      purified PrSAI1 displayed low pI and optimal pH values, specificity for beta
      fructofuranosides and inhibition by metallic ions and competitive inhibition by
      fructose. PrSAI1 is a typical vacuolar SAI that is actively involved in growth
      following both germination and attachment to host roots. In addition, germinated
      seeds displayed enhanced cell wall invertase activity (PrCWI) in comparison with
      preconditioned seeds, suggesting the contribution of this activity in the sink
      strength of infected roots during the subsequent step of root penetration. Our
      results show that PrSAI1 and, possibly, PrCWI constitute good targets for the
      development of new transgenic resistance in host plants using proteinaceous
      inhibitors or silencing strategies.

PMID- 21726370
TI  - Mapping studies of the Peach latent mosaic viroid reveal novel structural
      features.
AB  - Knowledge of the structure of a viroid is critically important to elucidate the
      roles played by the various RNA motifs in the steps of the viroid's life cycle. A
      new technique, RNA-selective 2'-hydroxyl acylation analysed by primer extension
      (SHAPE), has recently been shown to be fast, reliable and applicable to the study
      of various RNA molecules. Consequently, this method was used to probe sequence
      variants of Peach latent mosaic viroid (PLMVd). Initially, probing data from RNA
      strands of both polarities of the Siberian C variant confirmed the secondary
      structures previously determined using both conventional and fastidious
      approaches. Subsequently, analysis of an Alberta variant showed an identical
      structure for the strand of (-) polarity, but the (+) polarity strand exhibited
      two differences from the Siberian C variant: the P11-L11 stem-loop domain formed
      a cruciform structure, and nucleotides from loops L1 and L11 were involved in the
      formation of a pseudoknot. The existence of both of these motifs was confirmed by
      site-directed mutagenesis. The subsequent probing of 12 natural sequence variants
      led to the elucidation of the criteria governing the formation of this novel
      pseudoknot. Importantly, this study revealed that the heterogeneity of a viroid
      is not limited to its nucleotide sequence, but may also occur at the structural
      level.

PMID- 21726371
TI  - Physical association of pattern-triggered immunity (PTI) and effector-triggered
      immunity (ETI) immune receptors in Arabidopsis.
AB  - Plants possess two distinct types of immune receptor. The first type, pattern
      recognition receptors (PRRs), recognizes microbe-associated molecular patterns
      (MAMPs) and initiates pattern-triggered immunity (PTI) on recognition. FLS2 is a
      PRR, which recognizes a part of bacterial flagellin. The second type, resistance
      (R) proteins, recognizes pathogen effectors and initiates effector-triggered
      immunity (ETI) on recognition. RPM1, RPS2 and RPS5 are R proteins. Here, we
      provide evidence that FLS2 is physically associated with all three R proteins.
      Our findings suggest that signalling interactions occur between PTI and ETI at
      very early stages and/or that FLS2 forms a PTI signalling complex, some
      components of which are guarded by R proteins.

PMID- 21726372
TI  - Degeneration of hrpZ gene in Pseudomonas syringae pv. tabaci to evade tobacco
      defence: an arms race between tobacco and its bacterial pathogen.
AB  - The HrpZ harpin of Pseudomonas syringae is known to induce a hypersensitive
      response (HR) in some plants. In P. syringae pv. tabaci (Pta), the harpin gene
      hrpZ has been spontaneously disrupted by an internal deletion in its open reading
      frame and a frame shift. The loss of the ability of the recombinant harpin
      polypeptide of Pta to induce HR despite the high sensitivity of tobacco plants to
      harpin led us to investigate the meaning of the disrupted hrpZ gene in the
      virulence of Pta 6605. The hrpZ gene from P. syringae pv. pisi was introduced
      into wild-type (WT) Pta. The hrpZ-complemented Pta secreted harpin into the
      culture medium, but failed to cause disease symptoms by both infiltration and
      spray inoculation. Inoculation with the hrpZ-complemented Pta induced defence
      responses in tobacco plants, whereas the defence responses of tobacco plants were
      not prominent on inoculation with WT Pta. These results indicate that an ancestor
      of Pta might have disrupted hrpZ by an internal deletion to evade plant defences
      and confer the ability to cause disease in tobacco plants.

PMID- 21726373
TI  - Comparative analysis of the XopD type III secretion (T3S) effector family in
      plant pathogenic bacteria.
AB  - XopD is a type III effector protein that is required for Xanthomonas campestris
      pathovar vesicatoria (Xcv) growth in tomato. It is a modular protein consisting
      of an N-terminal DNA-binding domain, two ethylene-responsive element binding
      factor-associated amphiphilic repression (EAR) transcriptional repressor motifs
      and a C-terminal small ubiquitin-related modifier (SUMO) protease. In tomato,
      XopD functions as a transcriptional repressor, resulting in the suppression of
      defence responses at late stages of infection. A survey of available genome
      sequences for phytopathogenic bacteria revealed that XopD homologues are limited
      to species within three genera of Proteobacteria--Xanthomonas, Acidovorax and
      Pseudomonas. Although the EAR motif(s) and SUMO protease domain are conserved in
      all XopD-like proteins, variation exists in the length and sequence identity of
      the N-terminal domains. Comparative analysis of the DNA sequences surrounding
      xopD and xopD-like genes led to revised annotation of the xopD gene. Edman
      degradation sequence analysis and functional complementation studies confirmed
      that the xopD gene from Xcv encodes a 760-amino-acid protein with a longer N
      terminal domain than previously predicted. None of the XopD-like proteins studied
      complemented Xcv DeltaxopD mutant phenotypes in tomato leaves, suggesting that
      the N-terminus of XopD defines functional specificity. Xcv DeltaxopD strains
      expressing chimeric fusion proteins containing the N-terminus of XopD fused to
      the EAR motif(s) and SUMO protease domain of the XopD-like protein from X.
      campestris pathovar campestris strain B100 were fully virulent in tomato,
      demonstrating that the N-terminus of XopD controls specificity in tomato.

PMID- 21726374
TI  - Type III secretion-dependent host defence elicitation and type III secretion
      independent growth within leaves by Xanthomonas campestris pv. campestris.
AB  - In many plant-bacterial interactions, loss of the type III secretion system
      (T3SS) severely reduces bacterial growth, symptom causation and suppression of
      defences in host plants. In the present study of Xanthomonas campestris pv.
      campestris (Xcc), Xcc strain B305 grew better than strain B186 in Arabidopsis
      thaliana after hydathode inoculation, and B305 strains mutated to the loss of
      T3SS (DeltahrcC and/or DeltahrpE; also DeltahrcCDeltaflgBC) grew similarly to
      wild-type B305 in Arabidopsis leaves. Unlike Xcc strain B186, wild-type B305 was
      relatively inefficient in secreting the exogenous T3S effector AvrBsT, but
      DeltahrcC and/or DeltahrpE attenuated the disease symptoms caused by Xcc B305,
      showing that the partially compromised T3SS of this strain still promotes
      necrotic leaf symptoms. In contrast with the T3SS-dependent defence suppression
      that has been observed for some other plant pathogenic bacteria, the Xcc B186 and
      B305 wild-type strains (which are virulent on Arabidopsis) caused greater
      elicitation of host PR-1 and PR-5 expression and callose deposition in comparison
      with their respective T3SS mutants. A defence-suppressing/virulence-enhancing
      activity of the Xcc T3SS effector suite was detectable when co-inoculation with
      wild-type Xcc B186 increased the growth of DeltahrcC Xcc, but this activity did
      not prevent the above defence elicitation. Experiments using T3SS mutants and
      Arabidopsis fls2 mutants suggested that FLS2 does not play a prominent role in
      restriction of the examined Xcc strains. However, ectopic overexpression of the
      Pseudomonas syringae effector AvrPto promoted in planta growth of wild-type and
      DeltahrcC Xcc. In summary, the T3SS components or effector suite from virulent
      Xcc strains elicit some host defence responses, but suppress other defences and
      stimulate more severe disease symptoms, AvrPto-disruptable elements other than
      FLS2 apparently contribute to the host restriction of Xcc, and in some virulent
      Xcc strains the T3SS is not absolutely required for wild-type levels of bacterial
      growth within the plant.

PMID- 21726375
TI  - Negative regulation of defence signalling pathways by the EDR1 protein kinase.
AB  - The enhanced disease resistance 1 (edr1) mutant of Arabidopsis confers enhanced
      resistance to bacterial and fungal pathogens. To better understand how edr1
      mediated resistance occurs, we performed transcriptome analyses on wild-type and
      edr1 plants inoculated with the fungal pathogen Golovinomyces cichoracearum
      (powdery mildew). The expression of many known and putative defence-associated
      genes was more rapidly induced, and to higher levels, in edr1 plants relative to
      the wild-type. Many of the genes with elevated expression encoded WRKY
      transcription factors and there was enrichment for their binding sites in
      promoters of the genes upregulated in edr1. Confocal microscopy of transiently
      expressed EDR1 protein showed that a significant fraction of EDR1 was localized
      to the nucleus, suggesting that EDR1 could potentially interact with
      transcription factors in the nucleus. Analysis of gene ontology annotations
      revealed that genes associated with the endomembrane system, defence, reactive
      oxygen species (ROS) production and protein kinases were induced early in the
      edr1 mutant, and that elevated expression of the endomembrane system, defence and
      ROS-related genes was maintained for at least 4 days after infection.

PMID- 21726376
TI  - Altered trichothecene biosynthesis in TRI6-silenced transformants of Fusarium
      culmorum influences the severity of crown and foot rot on durum wheat seedlings.
AB  - An RNA silencing construct was used to alter mycotoxin production in the plant
      pathogenic fungus Fusarium culmorum, the incitant of crown and foot rot on wheat.
      The transformation of a wild-type strain and its nitrate reductase-deficient
      mutant with inverted repeat transgenes (IRTs) containing sequences corresponding
      to the trichothecene regulatory gene TRI6 was achieved using hygromycin B
      resistance as a selectable marker. Southern analysis revealed a variety of
      integration patterns of the TRI6 IRT. One transformant underwent homologous
      recombination with deletion of the endogenous TRI6 gene, whereas, in another
      transformant, the TRI6 IRT was not integrated into the genome. The TRI6 IRT did
      not alter the physiological characteristics, such as spore production,
      pigmentation or growth rate, on solid media. In most transformants, a high TRI6
      amplification signal was detected by quantitative reverse transcription
      polymerase chain reaction, corresponding to a TRI6-hybridizing smear of degraded
      fragments by Northern analysis, whereas TRI5 expression decreased compared with
      the respective nontransformed strain. Four transformants showed increased TRI5
      expression, which was correlated with a dramatic (up to 28-fold) augmentation of
      deoxynivalenol production. Pathogenicity assays on durum wheat seedlings
      confirmed that impairment of deoxynivalenol production in the TRI6 IRT
      transformants correlated with a loss of virulence, with decreased disease indices
      ranging from 40% to 80% in nine silenced strains, whereas the overproducing
      transformants displayed higher virulence compared with the wild-type.

PMID- 21726377
TI  - Evidence for involvement of Dicer-like, Argonaute and histone deacetylase
      proteins in gene silencing in Phytophthora infestans.
AB  - Gene silencing may have a direct or indirect impact on many biological processes
      in eukaryotic cells, and is a useful tool for the determination of the roles of
      specific genes. In this article, we report silencing in Phytophthora infestans,
      an oomycete pathogen of potato and tomato. Gene silencing is known to occur in P.
      infestans, but its genetic basis has yet to be determined. Genes encoding the
      major components of the RNA interference (RNAi) pathway, Dicer-like (Pidcl1),
      Argonaute (Piago1-5) and RNA-directed RNA polymerase (Pirdr1), were identified in
      the P. infestans genome by comparative genomics, together with families of other
      genes potentially involved in gene silencing, such as histone deacetylases,
      histone methyltransferases, DEAD helicases, chromodomain proteins and a class 1
      RNaseIII. Real-time reverse transcription-polymerase chain reaction demonstrated
      transcript accumulation for all candidate genes throughout the asexual lifecycle
      and plant infection, but at different levels of mRNA abundance. A functional
      assay was developed in which silencing of the sporulation-associated Picdc14 gene
      was released by the treatment of protoplasts with in vitro-synthesized double
      stranded RNAs homologous to Pidcl1, Piago1/2 and histone deacetylase Pihda1.
      These results suggest that the components of gene silencing, namely Dicer-like,
      Argonaute and histone deacetylase, are functional in P. infestans. Our data
      demonstrate that this oomycete possesses canonical gene silencing pathways
      similar to those of other eukaryotes.

PMID- 21726378
TI  - Applications of flow cytometry in plant pathology for genome size determination,
      detection and physiological status.
AB  - Flow cytometers are probably the most multipurpose laboratory devices available.
      They can analyse a vast and very diverse range of cell parameters. This technique
      has left its mark on cancer, human immunodeficiency virus and immunology
      research, and is indispensable in routine clinical diagnostics. Flow cytometry
      (FCM) is also a well-known tool for the detection and physiological status
      assessment of microorganisms in drinking water, marine environments, food and
      fermentation processes. However, flow cytometers are seldom used in plant
      pathology, despite FCM's major advantages as both a detection method and a
      research tool. Potential uses of FCM include the characterization of genome sizes
      of fungal and oomycete populations, multiplexed pathogen detection and the
      monitoring of the viability, culturability and gene expression of plant
      pathogens, and many others. This review provides an overview of the history,
      advantages and disadvantages of FCM, and focuses on the current applications and
      future possibilities of FCM in plant pathology.

PMID- 21726379
TI  - Expression of coordinately regulated defence response genes and analysis of their
      role in disease resistance in Medicago truncatula.
AB  - Microarray technology was used to identify the genes associated with disease
      defence responses in the model legume Medicago truncatula. Transcript profiles
      from M. truncatula cv. Jemalong genotype A17 leaves inoculated with
      Colletotrichum trifolii and Erysiphe pisi and roots infected with Phytophthora
      medicaginis were compared to identify the genes expressed in response to all
      three pathogens and genes unique to an interaction. The A17 genotype is resistant
      to C. trifolii and E. pisi, exhibiting a hypersensitive response after
      inoculation, and is moderately susceptible to P. medicaginis. Among the most
      strongly up-regulated genes in all three interactions were those encoding a
      hevein-like protein, thaumatin-like protein (TLP) and members of the pathogenesis
      response (PR)10 family. Transcripts of genes for enzymes in the phenylpropanoid
      pathway leading to the production of isoflavonoid phytoalexins increased
      dramatically in response to inoculation with the foliar pathogens. In P.
      medicaginis-inoculated roots, transcripts of genes in the phenylpropanoid pathway
      peaked at 5 days post-inoculation, when symptoms became visible. Transcript
      accumulation of three PR10 family members, a TLP and chalcone synthase (CHS) was
      assessed in M. truncatula genotype R108 plants. The R108 plants are resistant to
      C. trifolii and moderately susceptible to E. pisi and P. medicaginis. Transcript
      accumulation paralleled the stages of pathogen development. To evaluate the role
      of a TLP, a PR10 family member and CHS in disease resistance, transgenic R108
      plants containing interfering RNA (RNAi) constructs were produced. Reduced
      expression of PR10 and TLP had no effect on the disease phenotype, whereas
      reduced expression of CHS resulted in increased susceptibility to necrotrophic
      pathogens.

PMID- 21726380
TI  - Application of high-throughput genome sequencing to intrapathovar variation in
      Pseudomonas syringae.
AB  - One reason for the success of Pseudomonas syringae as a model pathogen has been
      the availability of three complete genome sequences since 2005. Now, at the
      beginning of 2011, more than 25 strains of P. syringae have been sequenced and
      many more will soon be released. To date, published analyses of P. syringae have
      been largely descriptive, focusing on catalogues of genetic differences among
      strains and between species. Numerous powerful statistical tools are now
      available that have yet to be applied to P. syringae genomic data for robust and
      quantitative reconstruction of evolutionary events. The aim of this review is to
      provide a snapshot of the current status of P. syringae genome sequence data
      resources, including very recent and unpublished studies, and thereby demonstrate
      the richness of resources available for this species. Furthermore, certain
      specific opportunities and challenges in making the best use of these data
      resources are highlighted.

PMID- 21726381
TI  - Amino acid changes in P3, and not the overlapping pipo-encoded protein, determine
      virulence of soybean mosaic virus on functionally immune Rsv1-genotype soybean.
AB  - A small open reading frame, termed 'pipo', is embedded in the P3 cistron of
      potyviruses. Currently, knowledge on pipo and its role(s) in the life cycle of
      potyviruses is limited. The P3 and helper-component proteinase (HC-Pro) cistrons
      of Soybean mosaic virus (SMV) harbour determinants affecting virulence on
      functionally immune Rsv1-genotype soybeans. Interestingly, a key virulence
      determinant of SMV on Rsv1-genotype soybeans (i.e. soybeans containing the Rsv1
      resistance gene) that resides at polyprotein codon 947 overlaps both P3 and a
      pipo-encoded codon. This raises the question of whether PIPO or P3 is the
      virulence factor. To answer this question, the corresponding pipo of an avirulent
      and two virulent strains of SMV were studied by comparative genomics, followed by
      syntheses and analyses of site-directed mutants. Our data demonstrate that the
      virulence of SMV on Rsv1-genotype soybeans is affected by P3 and not the
      overlapping pipo-encoded protein.

PMID- 21726382
TI  - The biocontrol bacterium Pseudomonas fluorescens Pf29Arp strain affects the
      pathogenesis-related gene expression of the take-all fungus Gaeumannomyces
      graminis var. tritici on wheat roots.
AB  - The main effects of antagonistic rhizobacteria on plant pathogenic fungi are
      antibiosis, fungistasis or an indirect constraint through the induction of a
      plant defence response. To explore different biocontrol mechanisms, an in vitro
      confrontation assay was conducted with the rhizobacterium Pseudomonas fluorescens
      Pf29Arp as a biocontrol agent of the fungus Gaeumannomyces graminis var. tritici
      (Ggt) on wheat roots. In parallel with the assessment of disease extension,
      together with the bacterial and fungal root colonization rates, the transcript
      levels of candidate fungal pathogenicity and plant-induced genes were monitored
      during the 10-day infection process. The bacterial inoculation of wheat roots
      with the Pf29Arp strain reduced the development of Ggt-induced disease expressed
      as attack frequency and necrosis length. The growth rates of Ggt and Pf29Arp,
      monitored through quantitative polymerase chain reaction of DNA amounts with a
      part of the Ggt 18S rDNA gene and a specific Pf29Arp strain detection probe,
      respectively, increased throughout the interactions. Bacterial antagonism and
      colonization had no significant effect on root colonization by Ggt. The
      expression of fungal and plant genes was quantified in planta by quantitative
      reverse transcription-polymerase chain reaction during the interactions thanks to
      the design of specific primers and an innovative universal reference system.
      During the early stages of the tripartite interaction, several of the fungal
      genes assayed were down-regulated by Pf29Arp, including two laccases, a beta-1,3
      exoglucanase and a mitogen-activated protein kinase. The plant host glutathione-S
      transferase gene was induced by Ggt alone and up-regulated by Pf29Arp bacteria in
      interaction with the pathogen. We conclude that Pf29Arp antagonism acts through
      the alteration of fungal pathogenesis and probably through the activation of host
      defences.

PMID- 21726383
TI  - p2 of rice stripe virus (RSV) interacts with OsSGS3 and is a silencing
      suppressor.
AB  - A rice cDNA library was screened by a galactosidase 4 (Gal4)-based yeast two
      hybrid system with Rice stripe virus (RSV) p2 as bait. The results revealed that
      RSV p2 interacted with a rice protein exhibiting a high degree of identity with
      Arabidopsis thaliana suppressor of gene silencing 3 (AtSGS3). The interaction was
      confirmed by bimolecular fluorescence complementation assay. SGS3 has been shown
      to be involved in sense transgene-induced RNA silencing and in the biogenesis of
      trans-acting small interfering RNAs (ta-siRNAs), possibly functioning as a
      cofactor of RNA-dependent RNA polymerase 6 (RDR6). Given the intimate
      relationships between virus and RNA silencing, further experiments were conducted
      to show that p2 was a silencing suppressor. In addition, p2 enhanced the
      accumulation and pathogenicity of Potato virus X in Nicotiana benthamiana. Five
      genes that have been demonstrated to be targets of TAS3-derived ta-siRNAs were up
      regulated in RSV-infected rice. The implications of these findings are discussed.

PMID- 21726384
TI  - Arabidopsis thaliana cdd1 mutant uncouples the constitutive activation of
      salicylic acid signalling from growth defects.
AB  - Arabidopsis genotypes with a hyperactive salicylic acid-mediated signalling
      pathway exhibit enhanced disease resistance, which is often coupled with growth
      and developmental defects, such as dwarfing and spontaneous necrotic lesions on
      the leaves, resulting in reduced biomass yield. In this article, we report a
      novel recessive mutant of Arabidopsis, cdd1 (constitutive defence without defect
      in growth and development1), that exhibits enhanced disease resistance associated
      with constitutive salicylic acid signalling, but without any observable
      pleiotropic phenotype. Both NPR1 (NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES1)
      dependent and NPR1-independent salicylic acid-regulated defence pathways are
      hyperactivated in cdd1 mutant plants, conferring enhanced resistance against
      bacterial pathogens. However, a functional NPR1 allele is required for the cdd1
      conferred heightened resistance against the oomycete pathogen Hyaloperonospora
      arabidopsidis. Salicylic acid accumulates at elevated levels in cdd1 and cdd1
      npr1 mutant plants and is necessary for cdd1-mediated PR1 expression and disease
      resistance phenotypes. In addition, we provide data which indicate that the cdd1
      mutation negatively regulates the npr1 mutation-induced hyperactivation of
      ethylene/jasmonic acid signalling.

PMID- 21726385
TI  - Durable broad-spectrum powdery mildew resistance in pea er1 plants is conferred
      by natural loss-of-function mutations in PsMLO1.
AB  - Loss-of-function alleles of plant-specific MLO (Mildew Resistance Locus O) genes
      confer broad-spectrum powdery mildew resistance in monocot (barley) and dicot
      (Arabidopsis thaliana, tomato) plants. Recessively inherited powdery mildew
      resistance in pea (Pisum sativum) er1 plants is, in many aspects, reminiscent of
      mlo-conditioned powdery mildew immunity, yet the underlying gene has remained
      elusive to date. We used a polymerase chain reaction (PCR)-based approach to
      amplify a candidate MLO cDNA from wild-type (Er1) pea. Sequence analysis of the
      PsMLO1 candidate gene in two natural er1 accessions from Asia and two er1
      containing pea cultivars with a New World origin revealed, in each case,
      detrimental nucleotide polymorphisms in PsMLO1, suggesting that PsMLO1 is Er1. We
      corroborated this hypothesis by restoration of susceptibility on transient
      expression of PsMLO1 in the leaves of two resistant er1 accessions. Orthologous
      legume MLO genes from Medicago truncatula and Lotus japonicus likewise
      complemented the er1 phenotype. All tested er1 genotypes showed unaltered
      colonization with the arbuscular mycorrhizal fungus, Glomus intraradices, and
      with nitrogen-fixing rhizobial bacteria. Our data demonstrate that PsMLO1 is Er1
      and that the loss of PsMLO1 function conditions durable broad-spectrum powdery
      mildew resistance in pea.

PMID- 21726386
TI  - The YopJ superfamily in plant-associated bacteria.
AB  - Bacterial pathogens employ the type III secretion system to secrete and
      translocate effector proteins into their hosts. The primary function of these
      effector proteins is believed to be the suppression of host defence responses or
      innate immunity. However, some effector proteins may be recognized by the host
      and consequently trigger a targeted immune response. The YopJ/HopZ/AvrRxv family
      of bacterial effector proteins is a widely distributed and evolutionarily diverse
      family, found in both animal and plant pathogens, as well as plant symbionts. How
      can an effector family effectively promote the virulence of pathogens on hosts
      from two separate kingdoms? Our understanding of the evolutionary relationships
      among the YopJ superfamily members provides an excellent opportunity to address
      this question and to investigate the functions and virulence strategies of a
      diverse type III effector family in animal and plant hosts. In this work, we
      briefly review the literature on YopJ, the archetypal member from Yersinia
      pestis, and discuss members of the superfamily in species of Pseudomonas,
      Xanthomonas, Ralstonia and Rhizobium. We review the molecular and cellular
      functions, if known, of the YopJ homologues in plants, and highlight the
      diversity of responses in different plant species, with a particular focus on the
      Pseudomonas syringae HopZ family. The YopJ superfamily provides an excellent
      foundation for the study of effector diversification in the context of wide
      ranging, co-evolutionary interactions.

PMID- 21726387
TI  - Targets of selection in a disease resistance network in wild tomatoes.
AB  - Studies combining comparative genomics and information on biochemical pathways
      have revealed that protein evolution can be affected by the amount of pleiotropy
      associated with a particular gene. The amount of pleiotropy, in turn, can be a
      function of the position at which a gene operates in a pathway and the pathway
      structure. Genes that serve as convergence points and have several partners (so
      called hubs) often show the greatest constraint and hence the slowest rate of
      protein evolution. In this article, we have studied five genes (Pto, Fen, Rin4,
      Prf and Pfi) in a defence signalling network in a wild tomato species, Solanum
      peruvianum. These proteins operate together and contribute to bacterial
      resistance in tomato. We predicted that Prf (and possibly Pfi), which serves as a
      convergence point for upstream signals, should show greater evolutionary
      constraint. However, we found instead that two of the genes which potentially
      interact with pathogen ligands, Rin4 and Fen, have evolved under strong
      evolutionary constraint, whereas Prf and Pfi, which probably function further
      downstream in the network, show evidence of balancing selection. This
      counterintuitive observation may be probable in pathogen defence networks,
      because pathogens may target positions throughout resistance networks to
      manipulate or nullify host resistance, thereby leaving a molecular signature of
      host-parasite co-evolution throughout a single network.

PMID- 21726388
TI  - Transcriptomic profiling of citrus fruit peel tissues reveals fundamental effects
      of phenylpropanoids and ethylene on induced resistance.
AB  - Penicillium spp. are the major postharvest pathogens of citrus fruit in
      Mediterranean climatic regions. The induction of natural resistance constitutes
      one of the most promising alternatives to avoid the environmental contamination
      and health problems caused by chemical fungicides. To understand the bases of the
      induction of resistance in citrus fruit against Penicillium digitatum, we have
      used a 12k citrus cDNA microarray to study transcriptional changes in the outer
      and inner parts of the peel (flavedo and albedo, respectively) of elicited
      fruits. The elicitor treatment led to an over-representation of biological
      processes associated with secondary metabolism, mainly phenylpropanoids and
      cellular amino acid biosynthesis and methionine metabolism, and the down
      regulation of genes related to biotic and abiotic stresses. Among
      phenylpropanoids, we detected the over-expression of a large subset of genes
      important for the synthesis of flavonoids, coumarins and lignin, especially in
      the internal tissue. Furthermore, these genes and those of ethylene biosynthesis
      showed the highest induction. The involvement of both phenylpropanoid and
      ethylene pathways was confirmed by examining changes in gene expression and
      ethylene production in elicited citrus fruit. Therefore, global results indicate
      that secondary metabolism, mainly phenylpropanoids, and ethylene play important
      roles in the induction of resistance in citrus fruit.

PMID- 21726389
TI  - Ectopic expression of the p23 silencing suppressor of Citrus tristeza virus
      differentially modifies viral accumulation and tropism in two transgenic woody
      hosts.
AB  - Citrus tristeza virus (CTV), a phloem-restricted closterovirus infecting citrus,
      encodes three different silencing suppressors (p25, p20 and p23), one of which
      (p23) is a pathogenicity determinant that induces aberrations resembling CTV
      symptoms when expressed ectopically in transgenic citrus hosts. In this article,
      the effect of p23 ectopic expression on virus infection was examined in sweet
      orange (SwO), a highly susceptible host, and sour orange (SO), which severely
      restricts CTV cell-to-cell movement. Transgenic plants of both species
      ectopically expressing p23, or transformed with an empty vector, were graft
      inoculated with the mild CTV isolate T385 or with CTV-BC1/GFP, a clonal strain
      derived from the severe isolate T36 carrying the gene for the green fluorescent
      protein (GFP). CTV distribution in infected tissues was assessed by direct tissue
      blot immunoassay and fluorescence emission, and virus accumulation was estimated
      by quantitative real-time reverse transcriptase-polymerase chain reaction. CTV
      accumulation in p23-expressing and control SwO plants was similar, whereas the
      viral load in transgenic SO expressing p23 was 10-10(5)  times higher than in the
      cognate control plants. Although few infection foci composed of a single cell
      were observed in the phloem of CTV-infected control SO, the number of foci in p23
      expressing plants was higher and usually comprised two to six cells, indicating
      viral cell-to-cell movement. CTV was detected in mesophyll protoplasts and cells
      from infected SO and SwO expressing p23, but not in similar protoplasts and cells
      from infected control plants. Our results show that the ectopic expression of p23
      enables CTV to escape from the phloem and, in addition, facilitates systemic
      infection of the resistant SO host. This is the first report of a viral-encoded
      protein that enhances virus accumulation and distribution in woody hosts.

PMID- 21726390
TI  - 454-pyrosequencing of Coffea arabica leaves infected by the rust fungus Hemileia
      vastatrix reveals in planta-expressed pathogen-secreted proteins and plant
      functions in a late compatible plant-rust interaction.
AB  - Coffee (Coffea arabica L.), one of the key export and cash crops in tropical and
      subtropical countries, suffers severe losses from the rust fungus Hemileia
      vastatrix. The transcriptome of H. vastatrix was analysed during a compatible
      interaction with coffee to obtain an exhaustive repertoire of the genes expressed
      during infection and to identify potential effector genes. Large-scale sequencing
      (454-GS-FLEX Titanium) of mixed coffee and rust cDNAs obtained from 21-day rust
      infected leaves generated 352 146 sequences which assembled into 22 774 contigs.
      In the absence of any reference genomic sequences for Coffea or Hemileia,
      specific trinucleotide frequencies within expressed sequence tags (ESTs) and
      blast homology against a set of dicots and basidiomycete genomes were used to
      distinguish pathogen from plant sequences. About 30% (6763) of the contigs were
      assigned to H. vastatrix and 61% (13 951) to C. arabica. The majority (60%) of
      the rust sequences did not show homology to any genomic database, indicating that
      they were potential novel fungal genes. In silico analyses of the 6763 H.
      vastatrix contigs predicted 382 secreted proteins and identified homologues of
      the flax rust haustorially expressed secreted proteins (HESPs) and bean rust
      transferred protein 1 (RTP1). These rust candidate effectors showed conserved
      amino-acid domains and conserved patterns of cysteine positions suggestive of
      conserved functions during infection of host plants. Quantitative reverse
      transcription-polymerase chain reaction profiling of selected rust genes revealed
      dynamic expression patterns during the time course of infection of coffee leaves.
      This study provides the first valuable genomic resource for the agriculturally
      important plant pathogen H. vastatrix and the first comprehensive C. arabica EST
      dataset.

PMID- 21726391
TI  - Genetic background matters: a plant-virus gene-for-gene interaction is strongly
      influenced by genetic contexts.
AB  - Evolutionary processes responsible for parasite adaptation to their hosts
      determine our capacity to manage sustainably resistant plant crops. Most plant
      parasite interactions studied so far correspond to gene-for-gene models in which
      the nature of the alleles present at a plant resistance locus and at a pathogen
      pathogenicity locus determine entirely the outcome of their confrontation. The
      interaction between the pepper pvr2 resistance locus and Potato virus Y (PVY)
      genome-linked protein VPg locus obeys this kind of model. Using synthetic
      chimeras between two parental PVY cDNA clones, we showed that the viral genetic
      background surrounding the VPg pathogenicity locus had a strong impact on the
      resistance breakdown capacity of the virus. Indeed, recombination of the
      cylindrical inclusion (CI) coding region between two PVY cDNA clones multiplied
      by six the virus capacity to break down the pvr2(3) -mediated resistance. High
      throughput sequencing allowed the exploration of the diversity of PVY populations
      in response to the selection pressure of the pvr2(3)  resistance. The CI chimera,
      which possessed an increased resistance breakdown capacity, did not show an
      increased mutation accumulation rate. Instead, selection of the most frequent
      resistance-breaking mutation seemed to be more efficient for the CI chimera than
      for the parental virus clone. These results echoed previous observations, which
      showed that the plant genetic background in which the pvr2(3)  resistance gene
      was introduced modified strongly the efficiency of selection of resistance
      breaking mutations by PVY. In a broader context, the PVY CI coding region is one
      of the first identified genetic factors to determine the evolvability of a plant
      virus.

PMID- 21726392
TI  - Analysis of the role of the coat protein N-terminal segment in Potato virus X
      virion stability and functional activity.
AB  - Previously, we have reported that intact Potato virus X (PVX) virions cannot be
      translated in cell-free systems, but acquire this capacity by the binding of PVX
      specific triple gene block protein 1 (TGBp1) or after phosphorylation of the
      exposed N-terminal segment of intravirus coat protein (CP) by protein kinases.
      With the help of in vitro mutagenesis, a nonphosphorylatable PVX mutant (denoted
      ST PVX) was prepared in which all 12 S and T residues in the 20-residue-long N
      terminal CP segment were substituted by A or G. Contrary to expectations, ST PVX
      was infectious, produced normal progeny and was translated in vitro in the
      absence of any additional factors. We suggest that the N-terminal PVX CP segment
      somehow participates in virion assembly in vivo and that CP subunits in ST
      virions may differ in structure from those in the wild-type (UK3 strain). In the
      present work, to test this suggestion, we performed a comparative tritium
      planigraphy study of CP structure in UK3 and ST virions. It was found that the
      profile of tritium incorporation into ST mutant virions in some CP segments
      differed from that of normal UK3 virions and from UK3 complexed with the PVX
      movement protein TGBp1. It is proposed that amino acid substitutions in ST CP and
      the TGBp1-driven remodelling of UK3 virions induce structural alterations in
      intravirus CPs. These alterations affect the predicted RNA recognition motif of
      PVX CP, but in different ways: for ST PVX, labelling is increased in alpha
      helices 6 and 7, whereas, in remodelled UK3, labelling is increased in the beta
      sheet strands beta3, beta4 and beta5.

PMID- 21726393
TI  - CorA, the magnesium/nickel/cobalt transporter, affects virulence and
      extracellular enzyme production in the soft rot pathogen Pectobacterium
      carotovorum.
AB  - Pectobacterium carotovorum (formerly Erwinia carotovora ssp. carotovora) is a
      phytopathogenic bacterium that causes soft rot disease, characterized by water
      soaked soft decay, resulting from the action of cell wall-degrading exoenzymes
      secreted by the pathogen. Virulence in soft rot bacteria is regulated by
      environmental factors, host and bacterial chemical signals, and a network of
      global and gene-specific bacterial regulators. We isolated a mini-Tn5 mutant of
      P. carotovorum that is reduced in the production of extracellular pectate lyase,
      protease, polygalacturonase and cellulase. The mutant is also decreased in
      virulence as it macerates less host tissues than its parent and is severely
      impaired in multiplication in planta. The inactivated gene responsible for the
      reduced virulent phenotype was identified as corA. CorA, a
      magnesium/nickel/cobalt membrane transporter, is the primary magnesium
      transporter for many bacteria. Compared with the parent, the CorA(-)  mutant is
      cobalt resistant. The mutant phenotype was confirmed in parental strain P.
      carotovorum by marker exchange inactivation of corA. A functional corA(+)  DNA
      from P. carotovorum restored exoenzyme production and pathogenicity to the
      mutants. The P. carotovorum corA(+)  clone also restored motility and cobalt
      sensitivity to a CorA(-)  mutant of Salmonella enterica. These data indicate that
      CorA is required for exoenzyme production and virulence in P. carotovorum.

PMID- 21726394
TI  - Analysis of Arabidopsis JAZ gene expression during Pseudomonas syringae
      pathogenesis.
AB  - The jasmonates (JAs) comprise a family of plant hormones that regulate several
      developmental processes and mediate responses to various abiotic and biotic
      stresses, including pathogens. JA signalling is manipulated by several strains of
      the bacterial pathogen Pseudomonas syringae, including P. syringae strain DC3000,
      using the virulence factor coronatine (COR) as a mimic of jasmonyl-L-isoleucine
      (JA-Ile). To better understand the JA-Ile-mediated processes contributing to P.
      syringae disease susceptibility, it is important to investigate the regulation of
      JA signalling during infection. In Arabidopsis thaliana, JASMONATE ZIM-DOMAIN
      (JAZ) proteins are negative regulators of JA signalling. The transcription factor
      JASMONATE INSENSITIVE1 (JIN1/ATMYC2) has been implicated in the regulation of JAZ
      gene expression. To investigate the regulation of JAZ genes during P. syringae
      pathogenesis, we examined JAZ gene expression during infection of Arabidopsis by
      DC3000. We found that eight of the 12 JAZ genes are induced during infection in a
      COR-dependent manner. Unexpectedly, the induction of the majority of JAZ genes
      during infection was not dependent on JIN1, indicating that JIN1 is not the only
      transcription factor regulating JAZ genes. A T-DNA insertion mutant and an RNA
      interference line disrupted for the expression of JAZ10, one of the few JAZ genes
      regulated by JIN1 during infection, exhibited enhanced JA sensitivity and
      increased susceptibility to DC3000, with the primary effect being increased
      disease symptom severity. Thus, JAZ10 is a negative regulator of both JA
      signalling and disease symptom development.

PMID- 21726395
TI  - Grapevine powdery mildew (Erysiphe necator): a fascinating system for the study
      of the biology, ecology and epidemiology of an obligate biotroph.
AB  - Few plant pathogens have had a more profound effect on the evolution of disease
      management than Erysiphe necator, which causes grapevine powdery mildew. When the
      pathogen first spread from North America to England in 1845, and onwards to
      France in 1847, 'germ theory' was neither understood among the general populace
      nor even generally accepted within the scientific community. Louis Pasteur had
      only recently reported the microbial nature of fermentation, and it would be
      another 30 years before Robert Koch would publish his proofs of the microbial
      nature of certain animal diseases. However, within 6 years after the arrival of
      the pathogen, nearly 6 million grape growers in France were routinely applying
      sulphur to suppress powdery mildew on nearly 2.5 million hectares of vineyards
      (Campbell, 2006). The pathogen has remained a focus for disease management
      efforts ever since. Because of the worldwide importance of the crop and its
      susceptibility to the disease, and because conventional management with modern,
      organic fungicides has been compromised on several occasions since 1980 by the
      evolution of fungicide resistance, there has also been a renewed effort worldwide
      to explore the pathogen's biology and ecology, its genetics and molecular
      interactions with host plants, and to refine current and suggest new management
      strategies. These latter aspects are the subject of our review. TAXONOMY: The
      most widely accepted classification follows. Family Erysiphaceae, Erysiphe
      necator Schw. [syn. Uncinula necator (Schw.) Burr., E. tuckeri Berk., U.
      americana Howe and U. spiralis Berk. & Curt; anamorph Oidium tuckeri Berk.].
      Erysiphe necator var. ampelopsidis was found on Parthenocissus spp. in North
      America according to Braun (1987), although later studies revealed isolates whose
      host range spanned genera, making the application of this taxon somewhat
      imprecise (Gadoury and Pearson, 1991). The classification of the genera before
      1980 was based on features of the mature ascocarp: (i) numbers of asci; and (ii)
      morphology of the appendages, in particular the appendage tips. The foregoing has
      been supplanted by phylogeny inferred from the internal transcribed spacer (ITS)
      of ribosomal DNA sequences (Saenz and Taylor, 1999), which correlates with
      conidial ontogeny and morphology (Braun et al., 2002). HOST RANGE: The pathogen
      is obligately parasitic on genera within the Vitaceae, including Vitis, Cissus,
      Parthenocissus and Ampelopsis (Pearson and Gadoury, 1992). The most economically
      important host is grapevine (Vitis), particularly the European grape, V.
      vinifera, which is highly susceptible to powdery mildew. Disease symptoms and
      signs: In the strictest sense, macroscopically visible mildew colonies are signs
      of the pathogen rather than symptoms resulting from its infection, but, for
      convenience, we describe the symptoms and signs together as the collective
      appearance of colonized host tissues. All green tissues of the host may be
      infected. Ascospore colonies are most commonly found on the lower surface of the
      first-formed leaves near the bark of the vine, and may be accompanied by a
      similarly shaped chlorotic spot on the upper surface. Young colonies appear
      whitish and those that have not yet sporulated show a metallic sheen. They are
      roughly circular, ranging in size from a few millimetres to a centimetre or more
      in diameter, and can occur singly or in groups that coalesce to cover much of the
      leaf. Senescent colonies are greyish, and may bear cleistothecia in various
      stages of development. Dead epidermal cells often subtend the colonized area, as
      natural mortality in the mildew colony, the use of fungicides, mycoparasites or
      resistance responses in the leaf result in the deaths of segments of the mildew
      colony and infected epidermal cells. Severely affected leaves usually senesce,
      develop necrotic blotches and fall prematurely. Infection of stems initially
      produces symptoms similar to those on leaves, but colonies on shoots are
      eventually killed as periderm forms, producing a dark, web-like scar on the cane
      (Gadoury et al., 2011). Inflorescences and berries are most susceptible when
      young, and can become completely coated with whitish mildew. The growth of the
      berry epidermal tissue stops when severely infected, which may result in
      splitting as young fruit expand. Berries in a transitional stage between
      susceptible and resistant (generally between 3 and 4 weeks after anthesis)
      develop diffuse, nonsporulating mildew colonies only visible under magnification.
      Diffuse colonies die as berries continue to mature, leaving behind a network of
      necrotic epidermal cells (Gadoury et al., 2007). Survival over winter as mycelium
      in buds results in a distinctive foliar symptom. Shoots arising from these buds
      may be heavily coated with fungal growth, stark white in colour and stand out
      like white flags in the vine, resulting in the term 'flag shoots'. More commonly,
      colonization of a flag shoot is less extensive, and infection of a single leaf,
      or of leaves on one side of the shoot only, is observed (Gadoury et al., 2011).

PMID- 21726396
TI  - Plasmodiophora brassicae: a review of an emerging pathogen of the Canadian canola
      (Brassica napus) crop.
AB  - Plasmodiophora brassicae causes clubroot disease in cruciferous plants, and is an
      emerging threat to Canadian canola (Brassica napus) production. This review
      focuses on recent studies into the pathogenic diversity of P. brassicae
      populations, mechanisms of pathogenesis and resistance, and the development of
      diagnostic tests for pathogen detection and quantification. TAXONOMY:
      Plasmodiophora brassicae is a soil-borne, obligate parasite within the class
      Phytomyxea (plasmodiophorids) of the protist supergroup Rhizaria. DISEASE
      SYMPTOMS: Clubroot development is characterized by the formation of club-shaped
      galls on the roots of affected plants. Above-ground symptoms include wilting,
      stunting, yellowing and premature senescence. DISEASE CYCLE: Plasmodiophora
      brassicae first infects the root hairs, producing motile zoospores that invade
      the cortical tissue. Secondary plasmodia form within the root cortex and, by
      triggering the expression of genes involved in the production of auxins,
      cytokinins and other plant growth regulators, divert a substantial proportion of
      plant resources into hypertrophic growth of the root tissues, resulting in the
      formation of galls. The secondary plasmodia are cleaved into millions of resting
      spores and the root galls quickly disintegrate, releasing long-lived resting
      spores into the soil. A serine protease, PRO1, has been shown to trigger resting
      spore germination. PHYSIOLOGICAL SPECIALIZATION: Physiological specialization
      occurs in populations of P. brassicae, and various host differential sets,
      consisting of different collections of Brassica genotypes, are used to
      distinguish among pathotypes of the parasite. DETECTION AND QUANTIFICATION: As P.
      brassicae cannot be cultured, bioassays with bait plants were traditionally used
      to detect the pathogen in the soil. More recent innovations for the detection and
      quantification of P. brassicae include the use of antibodies, quantitative
      polymerase chain reaction (qPCR) and qPCR in conjunction with signature fatty
      acid analysis, all of which are more sensitive than bioassays. RESISTANCE IN
      CANOLA: Clubroot-resistant canola hybrids, recently introduced into the Canadian
      market, represent an important new tool for clubroot management in this crop.
      Genetic resistance must be carefully managed, however, as it has been quickly
      overcome in other regions. At least three resistance genes and one or two
      quantitative trait loci are involved in conferring resistance to P. brassicae.
      Root hair infection still occurs in resistant cultivars, but secondary plasmodia
      often remain immature and unable to produce resting spores. Fewer cell wall
      breakages occur in resistant hosts, and spread of the plasmodium through cortical
      tissue is restricted. More information on the genetics of clubroot resistance in
      canola is needed to ensure more effective resistance stewardship. USEFUL
      WEBSITES: http://www.canolacouncil.org/clubroot/resources.aspx, http://tu
      dresden.de/die_tu_dresden/fakultaeten/fakultaet_mathematik_und_naturwissenschafte
      /fachrichtung_biologie/botanik/pflanzenphysiologie/clubroot,
      http://www.ohio.edu/people/braselto/plasmos/

PMID- 21726397
TI  - The role of lipopolysaccharide and peptidoglycan, two glycosylated bacterial
      microbe-associated molecular patterns (MAMPs), in plant innate immunity.
AB  - In an environment that is rich in potentially pathogenic microorganisms, the
      survival of higher eukaryotic organisms depends on efficient pathogen sensing and
      rapidly mounted defence responses. Such protective mechanisms are found in all
      multicellular organisms, and are collectively referred to as 'innate immunity'.
      Innate immunity is the first line of defence against invading microorganisms in
      vertebrates and the only line of defence in invertebrates and plants. Bacterial
      glycoconjugates, such as lipopolysaccharides (LPSs) from the outer membrane of
      Gram-negative bacteria and peptidoglycan (PGN) from the cell walls of both Gram
      positive and Gram-negative bacteria, have been found to act as elicitors of plant
      innate immunity. These conserved, indispensable, microbe-specific molecules are
      also referred to as 'microbe-associated molecular patterns' (MAMPs). MAMPs are
      recognized by the plant innate immune system through the action of pattern
      recognition receptors (PRRs). A greater insight into the mechanisms of MAMP
      recognition and the description of PRRs for different microbial glycoconjugates
      will have considerable impact on the improvement of plant health and disease
      resistance. Here, the current knowledge about LPS and PGN as MAMPs is reviewed.

PMID- 21726398
TI  - Building a mutant resource for the study of disease resistance in rice reveals
      the pivotal role of several genes involved in defence.
AB  - In Arabidopsis, gene expression studies and analysis of knock-out (KO) mutants
      have been instrumental in building an integrated view of disease resistance
      pathways. Such an integrated view is missing in rice where shared tools,
      including genes and mutants, must be assembled. This work provides a tool kit
      consisting of informative genes for the molecular characterization of the
      interaction of rice with the major fungal pathogen Magnaporthe oryzae. It also
      provides for a set of eight KO mutants, all in the same genotypic background, in
      genes involved in key steps of the rice disease resistance pathway. This study
      demonstrates the involvement of three genes, OsWRKY28, rTGA2.1 and NH1, in the
      establishment of full basal resistance to rice blast. The transcription factor
      OsWRKY28 acts as a negative regulator of basal resistance, like the orthologous
      barley gene. Finally, the up-regulation of the negative regulator OsWRKY28 and
      the down-regulation of PR gene expression early during M. oryzae infection
      suggest that the fungus possesses infection mechanisms that enable it to block
      host defences.

PMID- 21726399
TI  - Rice WRKY45 plays important roles in fungal and bacterial disease resistance.
AB  - Plant 'activators', such as benzothiadiazole (BTH), protect plants from various
      diseases by priming the plant salicylic acid (SA) signalling pathway. We have
      reported previously that a transcription factor identified in rice, WRKY45
      (OsWRKY45), plays a pivotal role in BTH-induced disease resistance by mediating
      SA signalling. Here, we report further functional characterization of WRKY45.
      Different plant activators vary in their action points, either downstream (BTH
      and tiadinil) or upstream (probenazole) of SA. Rice resistance to Magnaporthe
      grisea, induced by both types of plant activator, was markedly reduced in WRKY45
      knockdown (WRKY45-kd) rice, indicating a universal role for WRKY45 in chemical
      induced resistance. Fungal invasion into rice cells was blocked at most attempted
      invasion sites (pre-invasive defence) in WRKY45-overexpressing (WRKY45-ox) rice.
      Hydrogen peroxide accumulated within the cell wall underneath invading fungus
      appressoria or between the cell wall and the cytoplasm, implying a possible role
      for H(2)O(2) in pre-invasive defence. Moreover, a hypersensitive reaction-like
      reaction was observed in rice cells, in which fungal growth was inhibited after
      invasion (post-invasive defence). The two levels of defence mechanism appear to
      correspond to Type I and II nonhost resistances. The leaf blast resistance of
      WRKY45-ox rice plants was much higher than that of other known blast-resistant
      varieties. WRKY45-ox plants also showed strong panicle blast resistance. BTH
      induced resistance to Xanthomonas oryzae pv. oryzae was compromised in WRKY45-kd
      rice, whereas WRKY45-ox plants were highly resistant to this pathogen. However,
      WRKY45-ox plants were susceptible to Rhizoctonia solani. These results indicate
      the versatility and limitations of the application of this gene.

PMID- 21726401
TI  - Facilitative and antagonistic interactions between plant viruses in mixed
      infections.
AB  - Mixed infections of plant viruses are common in nature, and a number of important
      virus diseases of plants are the outcomes of interactions between causative
      agents. Multiple infections lead to a variety of intrahost virus-virus
      interactions, many of which may result in the generation of variants showing
      novel genetic features, and thus change the genetic structure of the viral
      population. Hence, virus-virus interactions in plants may be of crucial
      significance for the understanding of viral pathogenesis and evolution, and
      consequently for the development of efficient and stable control strategies. The
      interactions between plant viruses in mixed infections are generally categorized
      as synergistic or antagonistic. Moreover, mixtures of synergistic and
      antagonistic interactions, creating usually unpredictable biological and
      epidemiological consequences, are likely to occur in plants. The mechanisms of
      some of these are still unknown. This review aims to bring together the current
      knowledge on the most commonly occurring facilitative and antagonistic
      interactions between related or unrelated viruses infecting the same host plant.
      The best characterized implications of these interactions for virus-vector-host
      relationships are included. The terms 'synergism' and 'helper dependence' for
      facilitative virus-virus interactions, and 'cross-protection' and 'mutual
      exclusion' for antagonistic interactions, are applied in this article.

PMID- 21726400
TI  - Analysis of polymorphism and transcription of the effector gene Avr1b in
      Phytophthora sojae isolates from China virulent to Rps1b.
AB  - The effector gene Avr1b-1 of Phytophthora sojae determines the efficacy of the
      resistance gene Rps1b in soybean. The sequences of the Avr1b-1 locus in 34
      Chinese isolates of P. sojae were obtained and analysed by polymerase chain
      reaction (PCR) and inverse PCR. Four different alleles and a complete deletion
      mutation of the Avr1b-1 gene were identified. Molecular analysis of the deletion
      breakpoints in the Avr1b-1 locus revealed that an 8-kb DNA sequence containing
      Avr1b-1 was deleted and a 12.7-kb DNA sequence was inserted at the same locus. A
      truncated transposase gene was found and five transposable elements were
      predicted in the inserted sequence, suggesting that the deletion of Avr1b-1 might
      be attributed to transposon movement. The transcription of Avr1b-1 was analysed
      in virulent isolates containing four alleles of Avr1b-1 by real-time reverse
      transcription-PCR. In all virulent isolates, only those isolates containing the
      second allele transcripted Avr1b-1.

PMID- 21726402
TI  - The tomato UV-damaged DNA-binding protein-1 (DDB1) is implicated in pathogenesis
      related (PR) gene expression and resistance to Agrobacterium tumefaciens.
AB  - Plants defend themselves against potential pathogens via the recognition of
      pathogen-associated molecular patterns (PAMPs). However, the molecular mechanisms
      underlying this PAMP-triggered immunity (PTI) are largely unknown. In this study,
      we show that tomato HP1/DDB1, coding for a key component of the CUL4-based
      ubiquitin E3 ligase complex, is required for resistance to Agrobacterium
      tumefaciens. We found that the DDB1-deficient mutant (high pigment-1, hp1) is
      susceptible to nontumorigenic A. tumefaciens. The efficiency of callus generation
      from the hp1 cotyledons was extremely low as a result of the necrosis caused by
      Agrobacterium infection. On infiltration of nontumorigenic A. tumefaciens into
      leaves, the hp1 mutant moderately supported Agrobacterium growth and developed
      disease symptoms, but the expression of the pathogenesis-related gene SlPR1a1 and
      several PTI marker genes was compromised at different levels. Moreover, exogenous
      application of salicylic acid (SA) triggered SlPR1a1 gene expression and enhanced
      resistance to A. tumefaciens in wild-type tomato plants, whereas these SA
      regulated defence responses were abolished in hp1 mutant plants. Thus, HP1/DDB1
      may function through interaction with the SA-regulated PTI pathway in resistance
      against Agrobacterium infection.

PMID- 21726403
TI  - Mitochondrial quality control during inheritance is associated with lifespan and
      mother-daughter age asymmetry in budding yeast.
AB  - Fluorescence loss in photobleaching experiments and analysis of mitochondrial
      function using superoxide and redox potential biosensors revealed that
      mitochondria within individual yeast cells are physically and functionally
      distinct. Mitochondria that are retained in mother cells during yeast cell
      division have a significantly more oxidizing redox potential and higher
      superoxide levels compared to mitochondria in buds. Retention of mitochondria
      with more oxidizing redox potential in mother cells occurs to the same extent in
      young and older cells and can account for the age-associated decline in total
      cellular mitochondrial redox potential in yeast as they age from 0 to 5
      generations. Deletion of Mmr1p, a member of the DSL1 family of tethering proteins
      that localizes to mitochondria at the bud tip and is required for normal
      mitochondrial inheritance, produces defects in mitochondrial quality control and
      heterogeneity in replicative lifespan (RLS). Long-lived mmr1Delta cells exhibit
      prolonged RLS, reduced mean generation times, more reducing mitochondrial redox
      potential and lower mitochondrial superoxide levels compared to wild-type cells.
      Short-lived mmr1Delta cells exhibit the opposite phenotypes. Moreover, short
      lived cells give rise exclusively to short-lived cells, while the majority of
      daughters of long-lived cells are long lived. These findings support the model
      that the mitochondrial inheritance machinery promotes retention of lower
      functioning mitochondria in mother cells and that this process contributes to
      both mother-daughter age asymmetry and age-associated declines in cellular
      fitness.

PMID- 21726404
TI  - Vaccination-induced changes in human B-cell repertoire and pneumococcal IgM and
      IgA antibody at different ages.
AB  - It is well known that older people are more susceptible to morbidity and
      mortality from infectious diseases, particularly from pulmonary diseases such as
      pneumococcal pneumonia where vaccines do not provide efficient protection as in
      younger populations. We have previously shown that the B-cell repertoire in the
      old is reduced and hypothesise that this may contribute to the impaired humoral
      responses of the elderly. Here, we investigated the repertoire and antibody
      responses to winter vaccination in two age groups, aged 18-49 and 65-89. We found
      that the serum IgM and IgA pneumococcal responses were significantly impaired in
      the older group, with no difference in IgG levels. IGHM spectratype analysis
      seems to be the most promising in terms of its predictive ability for vaccine
      responses. Spectratypes showed a clear change in the repertoire at day 7 after
      vaccination, with a return to the baseline levels at day 28. The changes at day 7
      reflected expansion of IGH sequences that have smaller, more hydrophilic, CDR3
      regions, and these changes were attenuated in the older group. The older group
      was more likely to have spectratypes indicative of a reduced diversity at day 0
      and day 28. On average, the baseline repertoire in the older group was comprised
      of larger CDR3 regions than in the younger group. In conclusion, IgA and IgM
      responses are significantly impaired in the elderly pneumococcal response and are
      likely key mediators of protection. Hydrophilicity and/or small size of the IGH
      CDR3 appear to be important in these responses.

PMID- 21726405
TI  - Platelet reactive conformation and multimeric pattern of von Willebrand factor in
      acquired thrombotic thrombocytopenic purpura during acute disease and remission.
AB  - BACKGROUND: Binding of von Willebrand factor (VWF) multimers of ultra-large size
      to platelets is considered the triggering mechanism of microvascular thrombosis
      in thrombotic thrombocytopenic purpura (TTP). OBJECTIVE: To assess the potential
      of VWF-related measurements as markers of disease activity and severity in TTP.
      METHODS: VWF antigen (VWF:Ag), platelet glycoprotein-Ib-alpha binding
      conformation (GPIb-alpha/BC) and multimeric pattern were investigated in 74
      patients with acquired TTP during acute disease, remission or both and 73 healthy
      controls. In patients with both acute and remission samples available, VWF
      ristocetin co-factor activity (VWF:RCo) and collagen binding (VWF:CB) were also
      measured. The relationships of study measurements with the presence of acute
      disease and remission and with markers of disease severity were assessed.
      RESULTS: VWF:Ag and VWF-GPIb-alpha/BC were higher in TTP patients than controls
      (P < 0.001 and 0.004). However, there was no statistically significant difference
      in VWF-GPIb-alpha/BC between samples obtained during acute TTP and remission.
      Larger VWF multimers were frequently lacking in acute TTP patients, who displayed
      ultra-large multimers at remission. The degree of loss of larger VWF multimers
      correlated with the degree of abnormality of hemoglobin, platelet counts and
      serum lactate dehydrogenase (LDH) and was associated with low levels of both
      VWF:RCo/Ag and VWF:CB/Ag ratios. CONCLUSIONS: In TTP the platelet-binding
      conformation of VWF is not exclusively present in acute disease, nor is it
      associated with its clinical and laboratory severity. The loss of larger VWF
      multimers, accompanied by low VWF:RCo/Ag and VWF:CB/Ag ratio values, represents
      an index of disease activity and severity of acute TTP in patients with severe
      ADAMTS-13 deficiency.

PMID- 21726406
TI  - Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial
      cells.
AB  - Candida glabrata owes its success as a pathogen, in part, to a large repertoire
      of adhesins present on the cell surface. Our current knowledge of C. glabrata
      adhesins and their role in the interaction between host and pathogen is limited
      to work with only a single family of epithelial adhesins (Epa proteins). Here, we
      report on the identification and characterization of a family of
      glycosylphosphatidylinositol-anchored cell wall proteins in C. glabrata. These
      proteins are absent in both Saccharomyces cerevisiae and Candida albicans,
      suggesting that C. glabrata has evolved different mechanism(s) for interaction
      with host cells. In the current study, we present data on the characterization of
      Pwp7p (PA14 domain containing Wall Protein) and Aed1p (Adherence to Endothelial
      cells) of this family in the interaction of C. glabrata with human umbilical vein
      endothelial cells. The deletion of C. glabrata genes PWP7 and AED1 results in a
      significant reduction in adherence to endothelial cells compared with the wild
      type parent. These data indicate that C. glabrata utilizes these proteins for
      adherence to endothelial cells in vitro.

PMID- 21726407
TI  - Identification of a Zds-like gene ZDS3 as a new mediator of stress resistance,
      capsule formation and virulence of the human pathogenic yeast Cryptococcus
      neoformans.
AB  - The fungal Zds proteins are regulators of the serine/threonine phosphatase 2A
      (PP2A) and the protein kinase A. Here, we characterize a Zds-like gene ZDS3 that
      plays a broad range of roles in the basidiomycetous pathogenic yeast Cryptococcus
      neoformans. ZDS3 harbors the conserved activation domain ZDS_C of Zds proteins.
      By gene disruption, ZDS3 is shown to play roles in capsule production, cell wall
      integrity, growth at a high temperature, resistance to H(2)O(2) stress, osmotic
      pressures and glucose-dependent invasive growth on the agar. As a consequence,
      the disruption of ZDS3 resulted in complete loss of virulence in a mouse
      cryptococcosis model. The data suggest that ZDS3 is a novel mediator of the
      virulence of C. neoformans. Zds3 may serve as an antifungal drug target as no
      homologs are found in mammals.

PMID- 21726408
TI  - Rotundifolone-induced relaxation is mediated by BK(Ca) channel activation and
      Ca(v) channel inactivation.
AB  - Rotundifolone is the major constituent of the essential oil of Mentha x villosa
      Hudson. In preliminary studies, rotundifolone induced significant hypotensive,
      bradycardic and vasorelaxant effects in rats. Thus, to gain more insight into the
      pharmacology of rotundifolone, the aim of this study was to characterize the
      molecular mechanism of action involved in relaxation produced by rotundifolone.
      The relaxant effect was investigated in rat superior mesenteric arteries by using
      isometric tension measurements and whole-cell patch-clamp techniques.
      Rotundifolone relaxed phenylephrine-induced contractions in a concentration
      dependent manner. Pre-treatment with KCl (20 mM), charybdotoxin (10(-7) M) or
      tetraethylammonium (TEA 10(-3) or 3 * 10(-3) M) significantly attenuated the
      relaxation effect induced by rotundifolone. Additionally, whole-cell patch-clamp
      recordings were made in mesenteric smooth muscle cells and showed that
      rotundifolone significantly increased K(+) currents, and this effect was
      abolished by TEA (10(-3)  M), suggesting the participation of BK(Ca) channels.
      Furthermore, rotundifolone inhibited the vasoconstriction induced by CaCl(2) in
      depolarizing nominally Ca(2+) -free medium and antagonized the contractions
      elicited by an L-type Ca(2+) channel agonist, S(-)-Bay K 8644 (2 * 10(-7)  M),
      indicating that the vasodilatation involved inhibition of Ca(2+) influx through L
      type voltage-dependent calcium channels (Ca(v) type-L). Additionally,
      rotundifolone inhibited L-type Ca(2+) currents (I(Ca) L), affecting the voltage
      dependent activation of I(Ca) L and steady-state inactivation. Our findings
      suggest that rotundifolone induces vasodilatation through two distinct but
      complementary mechanisms that clearly depend on the concentration range used.
      Rotundifolone elicits an increase in the current density of BK(Ca) channels and
      causes a shift in the steady-state inactivation relationship for Ca(v) type-L
      towards more hyperpolarized membrane potentials.

PMID- 21726409
TI  - Life-threatening bupropion ingestion: is there a role for intravenous fat
      emulsion?
AB  - Intravenous fat emulsion (IFE) is emerging as a novel antidote in clinical
      toxicology. Its current usage is extending beyond local anaesthetic toxicity into
      management of severe toxicity from some lipophilic drugs. We present a 51-year
      old woman with severe bupropion toxicity whose haemodynamic status transiently
      improved after IFE. Serum analysis demonstrated an increase in serum
      concentration of hydroxybupropion, an active metabolite of bupropion, after IFE
      administration, lending support to one of the proposed mechanisms of IFE. A 51
      year-old woman presented to the emergency department with generalised tonic
      clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on
      her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium
      bicarbonate therapy, the patient developed profound hypotension refractory to
      high-dose norepinephrine. IFE was administered with haemodynamic improvement over
      the course of 30 min., followed by a significant decrease in norepinephrine
      requirement. The patient had an episode of ventricular tachycardia 24 hr after
      presentation, and received a second infusion of IFE. Analysis of serum for a
      panel of myocardial sodium channel blocking drugs revealed that significant
      bupropion ingestion had occurred. Bupropion poisoning may produce life
      threatening clinical effects, and IFE may be considered in cases of severe
      haemodynamic instability. Further studies would be instrumental in determining
      the optimal clinical situations for utilisation of IFE.

PMID- 21726410
TI  - Effects of the CYP2C9*1/*13 genotype on the pharmacokinetics of lornoxicam.
AB  - Lornoxicam is extensively metabolized by CYP2C9, and a CYP2C9*13 is one of the
      principal variant alleles in East Asian populations. The aim of this study was to
      evaluate the effects of CYP2C9*1/*13 on the pharmacokinetic parameters of
      lornoxicam in healthy individuals. A single oral dose of 8 mg lornoxicam was
      given to 22 Korean volunteers with different CYP2C9 genotypes (8, 8 and 6
      carriers of CYP2C9*1/*1, *1/*3 and *1/*13 genotypes, respectively). Lornoxicam
      and 5'-hydroxylornoxicam levels were analysed using HPLC-UV in plasma samples
      collected up to 24 hr after taking the drug. In individuals with CYP2C9*1/*13,
      lornoxicam had a higher C(max) (p < 0.001), a longer half-life (p < 0.001), a
      lower oral clearance (p < 0.001) and a higher area under the plasma concentration
      time curve from zero to infinity (AUC(inf) ) than in CYP2C9*1/*1 individuals (p <
      0.001). The C(max) and AUC(inf) of 5'-hydroxylornoxicam were lower in
      CYP2C9*1/*13 individuals than in CYP2C9*1/*1 individuals, but the half-life of 5'
      hydroxylornoxicam did not differ between the two groups. The half-life, oral
      clearance and AUC(inf) of lornoxicam were similar in individuals with
      CYP2C9*1/*13 and those with CYP2C9*1/*3. The C(max) , half-life and AUC(inf) of
      5'-hydroxylornoxicam were also similar in both groups, although C(max) was higher
      in CYP2C9*1/*13 individuals (p < 0.01). A CYP2C9*1/*13 genotype markedly reduced
      the conversion of lornoxicam to 5'-hydroxylornoxicam, to a similar extent as that
      observed with the CYP2C9*1/*3 genotype.

PMID- 21726411
TI  - Rosiglitazone decreases plasma levels of osteoprotegerin in a randomized clinical
      trial with type 2 diabetes patients.
AB  - Cardiovascular disease is the leading cause of death in patients with type 2
      diabetes mellitus (T2DM). We suggested that plasma osteoprotegerin (OPG), a
      strong, independent predictor of cardiovascular disease, could discriminate
      between anti-diabetic treatments depending on their benefits regarding
      cardiovascular disease. The South Danish Diabetes Study, an investigator-driven,
      randomized, controlled clinical trial lasting 2 years, was used to test this
      hypothesis in patient groups with different medication strategies (insulin aspart
      or NPH insulin, added either metformin/placebo or rosiglitazone/placebo). A total
      of 371 individuals were eligible for the study. Basic variables were analysed
      along with measurement of plasma OPG and HbA(1c) at the beginning and end of the
      study. Only rosiglitazone treatment caused a significant decrease in plasma OPG
      concentrations (p = 0.003), while no significant change was seen in the other
      treatment groups. The effect of rosiglitazone on plasma OPG remained significant
      in a univariate analysis adjusted for change in HbA(1c) (p = 0.013). Of note, the
      change in plasma OPG significantly correlated with HbA(1c) improvement in
      rosiglitazone-treated patients (R = 0.29, p = 0.0002), while this correlation was
      poor in those not receiving rosiglitazone (R = 0.06, p =0.48). Treatment with
      rosiglitazone among patients with T2DM reduces the concentration of plasma OPG.
      This is not seen with metformin despite similar reductions in HbA(1c) .
      Alteration in the OPG/RANKL pathway by glitazones may have implications for the
      understanding of both cardiovascular effects and bone side effects of the drug.

PMID- 21726412
TI  - Effect of age on systemic exposure and haematological toxicity of carboplatin in
      advanced non-small cell lung cancer patients.
AB  - The aim of this study was to evaluate systemic exposure to carboplatin and its
      haematological toxicity in patients with advanced non-small cell lung cancer both
      older and younger than 70 years when the target area under the curve (AUC) in
      elderly patients was reduced by 20%. For this purpose, a population
      pharmacokinetic model was developed and the haematological toxicity of the drug
      was assessed. A total of 33 patients received carboplatin on day 1 and
      gemcitabine (1250 mg/m(2) ) on days 1 and 8. This schedule was repeated every 21
      days. The Calvert-Crokcoft-Gault formula was employed to calculate a dose of
      carboplatin with a target AUC of 5 mg/min./mL in patients under 70 years and 4
      mg/min./mL in patients aged 70 or older. The data of 24 patients were treated for
      population modelling performed with the nonmem (University of California, San
      Francisco, CA, USA) approach. Haematological toxicity was evaluated for all 33
      patients enrolled in the study. The carboplatin systemic exposure measured by the
      AUC (mg/min./mL) was 5.98 (5.45; 6.51) and 5.36 (5.02; 5.69) for the younger
      patients and older groups, respectively. No significant differences were observed
      between the two groups with respect to rates of grade 3+ anaemia, neutropenia or
      thrombocytopenia. In clinical practice, a target AUC of 4 mg/min./mL carboplatin
      is applied to patients aged 70 and over, but the actual systemic exposure to the
      drug is higher. This supports a target AUC of 4 mg/min./mL carboplatin for
      patients older than 70 years when the dose is calculated by means of the Calvert
      Crokcoft-Gault formula.

PMID- 21726413
TI  - Effect of common exon variant (p.P364L) on drug glucuronidation by the human UDP
      glucuronosyltransferase 1 family.
AB  - The UDP-glucuronosyltransferases (UGTs) comprise a major excretion pathway for
      diverse endogenous and exogenous substrates. Relations are reported between
      polymorphisms of exon 1 of UGT1 and drug side effects or carcinogenesis, but few
      studies exist of common exon polymorphisms that exert influence throughout UGT1
      isoforms. We analysed the polymorphism c.1091C>T, resulting in the amino acid
      substitution of p.P364L, found on common exon 4. We studied 187 healthy, adult
      Japanese volunteers. The allele frequency was 0.0053. We investigated the effect
      of p.P364L on glucuronidation of beta-estradiol, acetaminophen, propofol,
      lamotrigine, imipramine and cyproheptadine in an in vitro expression study. The
      V(max)  values for beta-estradiol of p.P364L-UGT1A1, 1A3, 1A7, 1A8 and 1A10 were
      36.6%, 82.1%, 26.8%, 29.2% and 22.5%, respectively, of the corresponding wild
      type. Glucuronidation activity towards acetaminophen of p.P364L-UGT1A1, 1A6, 1A7,
      1A8, 1A9 and 1A10 was 50.3%, 46.4%, 17.2%, 44.1%, 5.0% and 42.8%, respectively,
      of wild-type. Glucuronidation activity towards propofol of p.P364L-UGT1A7, 1A8,
      1A9 and 1A10 was 44.0%, 49.8%, 29.0% and 71.1%, respectively, of wild-type.
      Substrate inhibition was observed in lamotrigine, cyproheptadine and imipramine
      glucuronidation by wild-type UGT1A4 but vanished for p.P364L. The presence of
      p.P364L near the UDP-glucuronic acid binding site could lead to extensive
      reduction of enzyme activity of many UGT1s. Our results suggest that p.P364L is
      an important mutation that could give rise to adverse effects of various drugs,
      or carcinogenesis. It is important to study common exon mutations because these
      can reduce activity of all UGT1 isoforms.

PMID- 21726414
TI  - Immunogenetics of ageing.
AB  - The ageing process is very complex. Human longevity is a multifactorial trait
      which is determined by genetic and environmental factors. Twin and family studies
      imply that up to 25% of human lifespan is heritable. The longevity gene
      candidates have generally fallen into the following categories: inflammatory and
      immune-related factors, stress response elements, mediators of glucose and lipid
      metabolism, components of DNA repair and cellular proliferation and mitochondrial
      DNA haplogroups. Because of the central role of HLA molecules in the development
      of protective immunity and the extraordinary degree of polymorphism of HLA genes,
      many studies have addressed the possible impact of these genes on human
      longevity. Most of the data available so far demonstrated a possible role of HLA
      class II specificities in human longevity but definitive evidence has remained
      elusive. Although the data are limited and controversial, it has been
      hypothesized that longevity could be associated with cytokine gene polymorphisms
      correlating with different levels of cytokine production, thereby modulating
      immune responses in health and disease. Because of the essential role of
      cytokines in immune responses, the regulation of cytokine gene expression and
      their polymorphic nature, the genetic variations of these loci with functional
      significance could be appropriate immunogenetic candidate markers implicated in
      the mechanism of successful ageing and longevity. In addition, several other
      genes such as Toll-like receptor genes, Cycloxygenases (COX)/Lipoxygenases (LOX),
      CCR5, NK receptor genes and MBL2 have been assessed as a possible biomarkers
      associated with ageing. This review will summarize the data on the role of these
      immune genes in human longevity.

PMID- 21726415
TI  - Crystal structures of Candida albicans dihydrofolate reductase bound to propargyl
      linked antifolates reveal the flexibility of active site loop residues critical
      for ligand potency and selectivity.
AB  - Candida albicans and Candida glabrata cause fungal bloodstream infections that
      are associated with significant mortality. As part of an effort to develop potent
      and selective antifolates that target dihydrofolate reductase (DHFR) from Candida
      species, we report three ternary crystal structures of C. albicans DHFR (CaDHFR)
      bound to novel propargyl-linked analogs. Consistent with earlier modeling
      results, these structures show that hydrophobic pockets in the binding site may
      be exploited to increase ligand potency. The crystal structures also confirm that
      loop residues Thr 58- Phe 66, which flank the active site and influence ligand
      potency and selectivity, adopt multiple conformations. To aid the development of
      a dual Candida spp. inhibitor, three new crystal structures of C. glabrata DHFR
      (CgDHFR) bound to similar ligands as those bound in the ternary structures of
      CaDHFR are also reported here. Loop residues 58-66 in CgDHFR and human DHFR are 1
      and 3 A closer to the folate binding site, respectively, than loop residues in
      CaDHFR, suggesting that a properly size ligand could be a potent and selective
      dual inhibitor of CaDHFR and CgDHFR.

PMID- 21726416
TI  - Identification of agents that induce apoptosis of multicellular tumour spheroids:
      enrichment for mitotic inhibitors with hydrophobic properties.
AB  - Cell-based anticancer drug screening generally utilizes rapidly proliferating
      tumour cells grown as monolayer cultures. Hit compounds from such screens are not
      necessarily effective on hypoxic and slowly proliferating cells in 3-D tumour
      tissue. The aim of this study was to examine the potential usefulness of 3-D
      cultured tumour cells for anticancer drug screening. We used colon carcinoma
      multicellular spheroids containing hypoxic and quiescent cells in core areas for
      this purpose. Three libraries (~11 000 compounds) were screened using
      antiproliferative activity and/or apoptosis as end-points. Screening of monolayer
      and spheroid cultures was found to identify different sets of hit compounds.
      Spheroid screening enriched for hydrophobic compounds: median XLogP values of 4.3
      and 4.4 were observed for the hits in two independent screening campaigns.
      Mechanistic analysis revealed that the majority of spheroid screening hits were
      microtubuli inhibitors. One of these inhibitors was examined in detail and found
      to be effective against non-dividing cells in the hypoxic centres of spheroids.
      Spheroid screening represents a conceptually new strategy for anticancer drug
      discovery. Our findings have implications for drug library design and hit
      selection in projects aimed to develop drugs for the treatment of solid tumours.

PMID- 21726417
TI  - Amyotrophic lateral sclerosis immunoglobulins G enhance the mobility of
      Lysotracker-labelled vesicles in cultured rat astrocytes.
AB  - AIM: We examined the effect of purified immunoglobulins G (IgG) from patients
      with amyotrophic lateral sclerosis (ALS) on the mobility and exocytotic release
      from Lysotracker-stained vesicles in cultured rat astrocytes. METHODS: Time-lapse
      confocal images were acquired, and vesicle mobility was analysed before and after
      the application of ALS IgG. The vesicle counts were obtained to assess cargo
      exocytosis from stained organelles. RESULTS: At rest, when mobility was monitored
      for 2 min in bath with Ca(2+), two vesicle populations were discovered: (1) non
      mobile vesicles (6.1%) with total track length (TL) < 1 MUm, averaging at 0.33 +/
      0.01 MUm (n = 1305) and (2) mobile vesicles (93.9%) with TL > 1 MUm, averaging
      at 3.03 +/- 0.01 MUm (n = 20,200). ALS IgG (0.1 mg mL(-1)) from 12 of 13 patients
      increased the TL of mobile vesicles by approx. 24% and maximal displacement (MD)
      by approx. 26% within 4 min, while the IgG from control group did not alter the
      vesicle mobility. The mobility enhancement by ALS IgG was reduced in
      extracellular solution devoid of Ca(2+), indicating that ALS IgG vesicle mobility
      enhancement involves changes in Ca(2+) homeostasis. To examine whether enhanced
      mobility relates to elevated Ca(2+) activity, cells were stimulated by 1 mm ATP,
      a cytosolic Ca(2+) increasing agent, in the presence (2 mm) and in the absence of
      extracellular Ca(2+). ATP stimulation triggered an increase in TL by approx. 7%
      and 12% and a decrease in MD by approx. 11% and 1%, within 4 min respectively.
      Interestingly, none of the stimuli triggered the release of vesicle cargo.
      CONCLUSION: Amyotrophic lateral sclerosis-IgG-enhanced vesicle mobility in
      astrocytes engages changes in calcium homeostasis.

PMID- 21726418
TI  - Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their
      potential relevance to gastrointestinal inflammation.
AB  - AIM: Plant cannabinoids, like Delta(9)-tetrahydrocannabinol (THC) and cannabidiol
      (CBD), activate/desensitize thermosensitive transient receptor potential (TRP)
      channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether
      cannabinoids also activate/desensitize two other 'thermo-TRP's', the TRP channels
      of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive
      cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the
      gastrointestinal tract. METHODS: TRP activity was assessed by evaluating
      elevation of [Ca(2+)](i) in rat recombinant TRPV3- and TRPV4-expressing HEK-293
      cells. TRP channel mRNA expression was measured by quantitative RT-PCR in the
      jejunum and ileum of mice treated with vehicle or the pro-inflammatory agent
      croton oil. RESULTS: (i) CBD and tetrahydrocannabivarin (THCV) stimulated TRPV3
      mediated [Ca(2+)](i) with high efficacy (50-70% of the effect of ionomycin) and
      potency (EC(50~) 3.7 MUm), whereas cannabigerovarin (CBGV) and cannabigerolic
      acid (CBGA) were significantly more efficacious at desensitizing this channel to
      the action of carvacrol than at activating it; (ii) cannabidivarin and THCV
      stimulated TRPV4-mediated [Ca(2+)](i) with moderate-high efficacy (30-60% of the
      effect of ionomycin) and potency (EC(50) 0.9-6.4 MUm), whereas CBGA, CBGV,
      cannabinol and cannabigerol were significantly more efficacious at desensitizing
      this channel to the action of 4-alpha-phorbol 12,13-didecanoate (4alpha-PDD) than
      at activating it; (iii) CBC reduced TRPV1beta, TRPV3 and TRPV4 mRNA in the
      jejunum, and TRPV3 and TRPV4 mRNA in the ileum of croton oil-treated mice.
      CONCLUSIONS: Cannabinoids can affect both the activity and the expression of
      TRPV1-4 channels, with various potential therapeutic applications, including in
      the gastrointestinal tract.

PMID- 21726419
TI  - Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia
      induced pulmonary vasoconstriction in a porcine model.
AB  - AIM: Our aim was to test the hypothesis that dual endothelin receptor blockade
      with tezosentan attenuates hypoxia-induced pulmonary vasoconstriction. METHODS:
      Fourteen anaesthetized, ventilated pigs, with a mean +/- SEM weight of 30.5 +/-
      0.6 kg, were studied, in normoxia (FiO(2) 0.21) and with tezosentan (5 mg kg(-1))
      infusion during (n = 7) or before (n = 7) hypoxia (FiO(2) 0.10). RESULTS:
      Compared to normoxia, hypoxia increased (P < 0.05) pulmonary vascular resistance
      (PVR) by 3.4 +/- 0.7 WU, mean pulmonary artery pressure by 13.7 +/- 1.3 mmHg,
      mean right atrial pressure by 1.9 +/- 0.4 mmHg and decreased (P < 0.02) systemic
      vascular resistance (SVR) by 5.2 +/- 2.1 WU. Pulmonary capillary wedge pressure
      (PCWP), mean aortic blood pressure, heart rate, cardiac output, stroke volume and
      blood-O(2)-consumption were unaltered (P = ns). Tezosentan infused during
      hypoxia, normalized PVR, decreased (P < 0.05) maximally mean pulmonary artery
      pressure by 7.5 +/- 0.8 mmHg, SVR by 5.8 +/- 0.7 WU, mean aortic blood pressure
      by 10.8 +/- 3.0 mmHg and increased (P < 0.04) stroke volume by 8.5 +/- 1.8 mL.
      Mean right atrial pressure, PCWP, heart rate, cardiac output and blood-O(2) 
      consumption were unaltered (P = ns). Tezosentan infused before hypoxia
      additionally attenuated approx. 70% of the initial mean pulmonary artery pressure
      increase and abolished the PVR increase, without additionally affecting the other
      parameters. CONCLUSION: Dual endothelin receptor blockade during hypoxia
      attenuates the 'sustained' acute pulmonary vasoconstrictor response by reducing
      the mean pulmonary artery pressure increase by approx. 62% and by normalizing
      PVR. Pre-treatment with tezosentan before hypoxia, additionally attenuates the
      initial hypoxia-induced mean pulmonary artery pressure rise by approx. 70% and
      abolishes the PVR increase, during stable circulatory conditions, without
      affecting oxygenation.

PMID- 21726420
TI  - Myeloperoxidase staining with diluted Giemsa with phosphate buffer of pH 6.8 as a
      counterstain.

PMID- 21726421
TI  - Three-year outcome of phase-specific early intervention for first-episode
      psychosis: a cohort study in Hong Kong.
AB  - AIM: Although phase-specific early intervention for first-episode psychosis has
      been implemented in many different parts of the world, limited medium-term
      outcome data are available in non-Western populations with relatively low mental
      health resources. The study aimed to determine the effectiveness of phase
      specific early intervention in first-episode psychosis. METHOD: In this cohort
      study, we compared the 3-year outcome of 700 first-episode psychosis patients who
      received phase-specific early intervention with that of 700 patients matched for
      age, sex and diagnosis who received standard psychiatric care prior to early
      intervention. Using a structured data acquisition procedure, we determined
      functional outcome, symptom levels, relapse, recovery, suicidal behaviour and
      service utilization from clinical records. RESULTS: Patients in the early
      intervention group had longer full-time employment or study (P<0.001), fewer days
      of hospitalization (P<0.001), less severe positive symptoms (P=0.006), less
      severe negative symptoms (P =0.001), fewer suicides (P=0.009) and fewer
      disengagements (P=0.002) than the historical control group. Additionally, more
      patients in the early intervention group experienced a period of recovery
      (P=0.001), but the two groups had similar rates of relapse (P=0.08) and durations
      of untreated psychosis (P=0.72). CONCLUSIONS: The 3-year outcome in phase
      specific early intervention compared favourably with that of standard psychiatric
      care, particularly with respect to functional outcome and reduction in
      hospitalizations, suicides and disengagements. However, intervention did not
      appear to reduce the rate of relapse.

PMID- 21726422
TI  - Social cognition deficits and the 'ultra high risk' for psychosis population: a
      review of literature.
AB  - AIM: A number of risk factors for developing a psychotic disorder have been
      investigated in the 'ultra high risk' (UHR) population, including neurocognitive
      abilities, social functioning and, more recently, social cognition. We aimed to
      review the literature on social cognition in the UHR population. METHODS:
      Literature was restricted to English articles and identified using Pubmed,
      Medline, PsychINFO and CINAHLplus, as well as the reference lists of published
      studies and reviews. Search terms included social cognition, theory of mind,
      emotion recognition, attributional style, social knowledge, social perception,
      'at risk mental state', psychosis prodrome 'clinical high risk' and 'ultra high
      risk'. Inclusion criteria were an outcome measure of a social cognition task and
      an UHR population defined by a structured validated instrument. RESULTS: Seven
      original research articles met the inclusion criteria, one of which was a
      conference abstract. One of the two studies that assessed theory of mind, two of
      the four studies that assessed emotion recognition and both the two studies that
      assessed social perception/knowledge found significant deficits in UHR patients.
      The single study that assessed attributional bias also reported differences in
      UHR patients compared with healthy controls. CONCLUSIONS: There is limited
      published literature on social cognitive performance in the UHR population.
      Despite this, deficits in certain social cognitive abilities do appear to be
      present, but further research with more reliable cross-cultural measures is
      needed. The characterization of social cognitive deficits in the UHR populations
      may aid in the identification of potential markers for development of a
      subsequent psychotic disorder, as well as targets for early intervention.

PMID- 21726423
TI  - Anterior capsule haptic fixation: a new technique for recentring subluxated IOLs.

PMID- 21726424
TI  - Corneal curvature, pachymetry, and endothelial cell density in Marfan syndrome.
AB  - PURPOSE: To evaluate corneal curvature, pachymetry, and endothelial cell density
      (ECD) in Marfan syndrome (MFS). METHODS: A case-control study in which K values,
      pachymetry, and ECD were compared in 39 MFS eyes and 40 control eyes matched for
      age and refraction was conducted. MFS eyes with lens subluxation also were
      compared with eyes without subluxation. RESULTS: The mean K(med) value in MFS
      eyes was lower than in the control eyes, 42.2 +/- 1.9 versus 43.4 +/- 1.4
      dioptres (D), respectively (p = 0.02). Fifteen MFS eyes (38%) and three control
      eyes (8%) had K(med) values below 41.5 D (p = 0.0012). MFS eyes had generally
      more corneal astigmatism than control eyes, 1.1 +/- 0.9 versus 0.8 +/- 0.4 D (p =
      0.035), and MFS eyes with lens subluxation had more corneal astigmatism than
      those without, 1.6 +/- 1.1 versus 0.6 +/- 0.3 D (p = 0.0002). Nine MFS eyes with
      corneal astigmatism exceeding 1.5 D also had a subluxated lens. No eyes had
      keratoconus. The mean pachymetry value was lower in MFS eyes compared to the
      controls, 485 +/- 54.5 versus 514 +/- 37.3 MUm (p = 0.007); 24 MFS eyes (62%) and
      10 control eyes (25%) had measurements below 500 MUm (p = 0.01). The mean ECD
      values were similar in MFS and control eyes, 2815 +/- 430 versus 2858 +/- 458
      cells/mm(2) (p = 0.66). The mean K value, pachymetry, and ECD values did not
      differ between MFS eyes with and without lens subluxation. CONCLUSION: Decreased
      K values and pachymetry could indicate MFS regardless of subluxation. High
      corneal astigmatism is associated with subluxation in MFS. Subluxation should be
      identified in MFS eyes with high corneal astigmatism.

PMID- 21726425
TI  - Scleral buckling in rhegmatogenous retinal detachment with concomitant full
      thickness macular hole.

PMID- 21726426
TI  - Tear meniscus measurement in nasolacrimal duct obstruction patients with Fourier
      domain optical coherence tomography: novel three-point capture method.
AB  - PURPOSE: Fourier-domain optical coherence tomography (FD ODT) for the evaluation
      of marginal tear film has not been performed in patients with watery eye or in a
      controlled study. We used FD OCT to evaluate the height of the lower lid tear
      film at three points in normal adults and compared it with two watery eye groups.
      METHODS: We prospectively evaluated with FD OCT 25 normal subjects and 44
      patients with a watery eye. Twenty-three patients with primary acquired
      nasolacrimal duct obstruction (PANDO) and 21 patients with functional
      nasolacrimal duct obstruction (FNLDO) were enrolled. Three images were obtained
      by three vertical FD OCT scans centred on the lower eyelid and inferior cornea,
      the medial limbus and the lateral limbus. The tear meniscus height (TMH), tear
      meniscus depth (TMD) and tear meniscus area (TMA) were measured with computer
      calipers and compared at three points between the two groups. RESULTS: Watery
      eyes have significantly greater median TMHs at three points (medial: 584 MUm,
      central: 592 MUm, lateral: 470 MUm) than controls (274, 291, 205 MUm, p < 0.001).
      Medial and central TMHs were higher than lateral TMH in controls and watery eyes.
      TMD and TMA also increased significantly in watery eyes (p < 0.001). There was a
      significant increase in central TMH compared to medial TMH in FNLDOs than in
      PANDOs (p < 0.05). CONCLUSION: Fourier-domain OCT is a valuable clinical tool in
      the evaluation of TMH in normal and watery eyes. TMH at three points can be a
      useful clinical parameter that investigates changes of lower tear meniscus
      pattern in both PANDO and FNLDO groups.

PMID- 21726427
TI  - Panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab for
      high-risk proliferative diabetic retinopathy.
AB  - PURPOSE: To evaluate the effects of panretinal photocoagulation (PRP) compared
      with PRP plus intravitreal injection of 0.5 mg of ranibizumab (IVR) in patients
      with high-risk proliferative diabetic retinopathy (PDR). METHODS: Prospective
      study included patients with high-risk PDR and no prior laser treatment randomly
      assigned to receive PRP (PRP group) or PRP plus IVR (PRPplus group). PRP was
      administered in two sessions (weeks 0 and 2), and IVR was administered at the end
      of the first laser session in the PRPplus group. Standardized ophthalmic
      evaluations including best-corrected visual acuity (BCVA) measured according to
      the methods used in the Early Treatment Diabetic Retinopathy Study (BCVA),
      fluorescein angiography to measure area of fluorescein leakage (FLA) and optical
      coherence tomography (OCT) for the assessment of central subfield macular
      thickness (CSMT), were performed at baseline and at weeks 16 (+/- 2), 32 (+/- 2)
      and 48 (+/- 2). RESULTS: Twenty-nine of 40 patients (n = 29 eyes) completed the
      48-week study follow-up period. At baseline, mean +/- SE FLA (mm(2)) was 9.0 +/-
      1.3 and 11.7 +/- 1.3 (p = 0.1502); BCVA (logMAR) was 0.31 +/- 0.05 and 0.27 +/-
      0.06 (p = 0.6645); and CSMT (MUm) was 216.3 +/- 10.7 and 249.4 +/- 36.1 (p =
      0.3925), in the PRP and PRPplus groups, respectively. There was a significant (p
      < 0.05) FLA reduction at all study visits in both groups, with the reduction
      observed in the PRPplus group significantly larger than that in the PRP group at
      week 48 (PRP = 2.9 +/- 1.3 mm(2) ; PRPplus = 5.8 +/- 1.3 mm(2) ; p = 0.0291).
      Best-corrected visual acuity worsening was observed at 16, 32 and 48 weeks after
      treatment in the PRP group (p < 0.05), while no significant BCVA changes were
      observed in the PRPplus group. A significant CSMT increase was observed in the
      PRP group at all study visits, while a significant decrease in CSMT was observed
      in the PRPplus group at week 16, and no significant difference in CSMT from
      baseline was observed at weeks 32 and 48. CONCLUSIONS: Intravitreal ranibizumab
      after PRP was associated with a larger reduction in FLA at week 48 compared with
      PRP alone in eyes with high-risk PDR, and the adjunctive use of IVR appears to
      protect against the modest visual acuity loss and macular swelling observed in
      eyes treated with PRP alone.

PMID- 21726428
TI  - Topical treatment for 1 week with latanoprost but not diclofenac reduces the
      diameter of dilated retinal arterioles in patients with type 1 diabetes mellitus
      and mild retinopathy.
AB  - PURPOSE: Diabetic retinopathy is characterised by morphological lesions secondary
      to retinal vascular impairment, and it is assumed that changes in the diameter
      regulation of retinal arterioles are involved in the disease pathogenesis. It has
      previously been shown that prostaglandin F2alpha can constrict retinal arterioles
      in vitro. In the present study, we investigated whether a similar effect could be
      achieved by topical administration in diabetic patients with dilated retinal
      arterioles and retinopathy. METHODS: Twenty-two type 1 diabetic patients with
      mild retinopathy and twenty-four matched normal controls were randomized to
      topical treatment with the prostaglandin F2alpha agonist latanoprost twice daily
      for 1 week, followed by similar treatment with the cyclo-oxygenase inhibitor
      diclofenac, or to receive the two medications in the reverse order. The Dynamic
      Vessel Analyzer was used to assess the effect of the interventions on the resting
      diameter of retinal vessels and on the diameter response of retinal arterioles to
      increased blood pressure (BP) induced by isometric exercise and flicker
      stimulation. RESULTS: Latanoprost reduced the resting diameter of retinal
      arterioles significantly in patients with diabetes (p = 0.01), but had no effect
      on normal persons. Diclofenac had no effect on the resting diameter of arterioles
      in either of the groups. The diameter responses to increased BP and flicker
      stimulation were not significantly changed by any of the treatments. CONCLUSION:
      Long-term prospective studies are needed to study the effect of topical treatment
      with latanoprost on the consequences of retinal hyperperfusion in retinal
      vascular diseases such as diabetic retinopathy.

PMID- 21726429
TI  - Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed
      TGFbeta1-signaling and increased Galectin-3 expression: a histological study on
      biopsies.
AB  - BACKGROUND: Bisphosphonate associated osteonecrosis of the jaw (BRONJ) implies an
      impairment in oral hard- and soft tissue repair. An understanding of the signal
      transduction alterations involved can inform therapeutic strategies. Transforming
      growth factor beta1 (TGFbeta1) is a critical regulator of tissue repair; galectin
      3 mediates tissue differentiation and specifically modulates periodontopathic
      bacterial infection. The aim of this study was to compare the expression of
      TGFbeta1-related signaling molecules and Galectin-3 in BRONJ-affected and healthy
      mucosal tissues. To discriminate between BRONJ-specific impairments in TGFbeta1
      signaling and secondary inflammatory changes, the results were compared to the
      expression of TGFbeta1 and Galectin-3 in mucosal tissues with osteoradionecrosis.
      METHODS: Oral mucosal tissue samples with histologically-confirmed BRONJ (n =
      20), osteoradionecrosis (n = 20), and no lesions (normal, n = 20) were processed
      for immunohistochemistry. Automated staining with an alkaline phosphatase-anti
      alkaline phosphatase kit was used to detect TGFbeta1, Smad-2/3, Smad-7, and
      Galectin-3. We semiquantitatively assessed the ratio of stained cells/total
      number of cells (labeling index, Bonferroni-adjustment). RESULTS: TGFbeta1 and
      Smad-2/3 were significantly decreased (p < 0.032 and p(0.028, respectively) in
      the BRONJ samples and significantly increased (p < 0.04 and p <0.043,
      respectively) in the osteoradionecrosis samples compared to normal tissue. Smad-7
      was significantly increased (p < 0.031) in the BRONJ group and significantly
      decreased (p < 0.026) in the osteoradionecrosis group. Galectin-3 staining was
      significantly (p < 0.025) increased in both the BRONJ and the osteoradionecrosis
      (p < 0.038) groups compared to the normal tissue group. However, Galectin-3
      expression was significantly higher in the BRONJ samples than in the
      osteoradionecrosis samples (p < 0.044). CONCLUSION: Our results showed that
      disrupted TGFbeta1 signaling was associated with delayed periodontal repair in
      BRONJ samples. The findings also indicated that impairments in TGFbeta1-signaling
      were different in BRONJ compared to osteoradionecrosis. BRONJ appeared to be
      associated with increased terminal osseous differentiation and decreased soft
      tissue proliferation. The increase in Galectin-3 reflected the increase in
      osseous differentiation of mucoperiosteal progenitors, and this might explain the
      inflammatory anergy observed in BRONJ-affected soft tissues. The results
      substantiated the clinical success of treating BRONJ with sequestrectomy,
      followed by strict mucosa closure. BRONJ can be further elucidated by
      investigating the specific intraoral osteoimmunologic status.

PMID- 21726430
TI  - Robustness of genome-wide scanning using archived dried blood spot samples as a
      DNA source.
AB  - BACKGROUND: The search to identify disease-susceptible genes requires access to
      biological material from numerous well-characterized subjects. Archived residual
      dried blood spot (DBS) samples, also known as Guthrie cards, from national
      newborn screening programs may provide a DNA source for entire populations.
      Combined with clinical information from medical registries, DBS samples could
      provide a rich source for productive research. However, the amounts of DNA which
      can be extracted from these precious samples are minute and may be prohibitive
      for numerous genotypings. Previously, we demonstrated that DBS DNA can be whole
      genome amplified and used for reliable genetic analysis on different platforms,
      including genome-wide scanning arrays. However, it remains unclear whether this
      approach is workable on a large sample scale. We examined the robustness of using
      DBS samples for whole-genome amplification following genome-wide scanning, using
      arrays from Illumina and Affymetrix. RESULTS: This study is based on 4,641 DBS
      samples from the Danish Newborn Screening Biobank, extracted for three separate
      genome-wide association studies. The amount of amplified DNA was significantly (P
      < 0.05) affected by the year of storage and storage conditions. Nine (0.2%) DBS
      samples failed whole-genome amplification. A total of 4,586 (98.8%) samples met
      our criterion of success of a genetic call-rate above 97%. The three studies used
      different arrays, with mean genotyping call-rates of 99.385% (Illumina Infinium
      Human610-Quad), 99.722% (Illumina Infinium HD HumanOmni1-Quad), and 99.206%
      (Affymetrix Axiom Genome-Wide CEU). We observed a concordance rate of 99.997% in
      the 38 methodological replications, and 99.999% in the 27 technical replications.
      Handling variables such as time of storage, storage conditions and type of filter
      paper were shown too significantly (P < 0.05) affect the genotype call-rates in
      some of the arrays, although the effect was minimal. CONCLUSION: Our study
      indicates that archived DBS samples from the Danish Newborn Screening Biobank
      represent a reliable resource of DNA for whole-genome amplification and
      subsequent genome-wide association studies. With call-rates equivalent to high
      quality DNA samples, our results point to new opportunities for using the
      neonatal biobanks available worldwide in the hunt for genetic components of
      disease.

PMID- 21726431
TI  - Global Health Initiatives and aid effectiveness: insights from a Ugandan case
      study.
AB  - BACKGROUND: The emergence of Global Health Initiatives (GHIs) has been a major
      feature of the aid environment of the last decade. This paper seeks to examine in
      depth the behaviour of two prominent GHIs in the early stages of their operation
      in Uganda as well as the responses of the government. METHODS: The study adopted
      a qualitative and case study approach to investigate the governance of aid
      transactions in Uganda. Data sources included documentary review, in-depth and
      semi-structured interviews and observation of meetings. Agency theory guided the
      conceptual framework of the study. RESULTS: The Ugandan government had a stated
      preference for donor funding to be channelled through the general or sectoral
      budgets. Despite this preference, two large GHIs opted to allocate resources and
      deliver activities through projects with a disease-specific approach. The mixed
      motives of contributor country governments, recipient country governments and GHI
      executives produced incentive regimes in conflict between different aid
      mechanisms. CONCLUSION: Notwithstanding attempts to align and harmonize donor
      activities, the interests and motives of the various actors (GHIs and different
      parts of the government) undermine such efforts.

PMID- 21726432
TI  - MIA is a potential biomarker for tumour load in neurofibromatosis type 1.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a frequent genetic disease
      characterized by multiple benign tumours with increased risk for malignancy.
      There is currently no biomarker for tumour load in NF1 patients. METHODS: In situ
      hybridization and quantitative real-time polymerase reaction were applied to
      investigate expression of cartilage-specific genes in mice bearing conditional
      inactivation of NF1 in the developing limbs. These mice do not develop tumours
      but recapitulate aspects of NF1 bone dysplasia, including deregulation of
      cartilage differentiation. It has been recently shown that NF1 tumours require
      for their growth the master regulator of cartilage differentiation SOX9. We thus
      hypothesized that some of the cartilage-specific genes deregulated in an Nf1Prx1
      mouse model might prove to be relevant biomarkers of NF1 tumours. We tested this
      hypothesis by analyzing expression of the SOX9 target gene product melanoma
      inhibitory activity/cd-rap (MIA) in tumour and serum samples of NF1 patients.
      RESULTS: Increased expression of Mia was found in Nf1-deficient cartilage in
      mice. In humans, MIA was expressed in all NF1-related tumours and its serum
      levels were significantly higher in NF1 patients than in healthy controls. Among
      NF1 patients, MIA serum levels were significantly higher in those with plexiform
      neurofibromas and in those with large number of cutaneous (> 1,000) or
      subcutaneous (> 100) neurofibromas than in patients without such tumours. Most
      notably, MIA serum levels correlated significantly with internal tumour burden.
      CONCLUSIONS: MIA is a potential serum biomarker of tumour load in NF1 patients
      which could be useful in following the disease course and monitoring the efficacy
      of therapies.

PMID- 21726433
TI  - Experience of sexual coercion and risky sexual behavior among Ugandan university
      students.
AB  - BACKGROUND: Growing worldwide evidence shows that the experience of sexual
      coercion is fairly prevalent among young people and is associated with risky
      sexual behavior thereafter. The causal mechanisms behind this are unclear but may
      be dependent on specific contextual determinants. Little is known about factors
      that could buffer the negative effects of coercion. The aim of this study was to
      assess the association between the experience of sexual coercion and risky sexual
      behavior among university students of both sexes in Uganda. METHODS: In 2005, 980
      (80%) out of a total of 1,220 students enrolled in Mbarara University of Science
      and Technology in Uganda participated in a self-administered questionnaire
      covering socio-demographic and religious factors, social capital, mental health,
      alcohol use, and sexual behavior. A validated scale of six items was used to
      assess the experience of sexual coercion. Logistic regression analyses were
      applied to control for confounders. Potential buffering factors were analyzed by
      testing for effect modification. RESULTS: Fifty-nine percent of those who
      responded had previously had sexual intercourse. Among the male students 29.0%,
      and among the female students 33.1% reported having had some experience of sexual
      coercion. After controlling for age, gender, and educational level of household
      of origin, role of religion and trust in others sexual coercion was found to be
      statistically significantly associated with previously had sex (OR 1.6, 95% CI;
      1.1-2.3), early sexual debut (OR 2.4, 95% CI; 1.5-3.7), as well as with having
      had a great number of sexual partners (OR 1.9, 95% CI; 1.2-3.0), but not with
      inconsistent condom use.Scoring low on an assessment of mental health problems,
      reporting high trust in others, or stating that religion played a major role in
      one's family of origin seemed to buffer the negative effect that the experience
      of sexual coercion had on the likelihood of having many sexual partners.
      CONCLUSION: The findings of this study suggest that the experience of sexual
      coercion is common among youth/young adults in Uganda and is subsequently
      associated with risky sexual behavior in both sexes. The existence of individual
      and contextual factors that buffer the effects mentioned was also demonstrated.
      In the Ugandan context, this has implications for policy formulation and the
      implementation of preventive strategies for combating HIV/AIDS.

PMID- 21726434
TI  - Framing international trade and chronic disease.
AB  - There is an emerging evidence base that global trade is linked with the rise of
      chronic disease in many low and middle-income countries (LMICs). This linkage is
      associated, in part, with the global diffusion of unhealthy lifestyles and health
      damaging products posing a particular challenge to countries still facing high
      burdens of communicable disease. We developed a generic framework which depicts
      the determinants and pathways connecting global trade with chronic disease. We
      then applied this framework to three key risk factors for chronic disease:
      unhealthy diets, alcohol, and tobacco. This led to specific 'product pathways',
      which can be further refined and used by health policy-makers to engage with
      their country's trade policy-makers around health impacts of ongoing trade treaty
      negotiations, and by researchers to continue refining an evidence base on how
      global trade is affecting patterns of chronic disease. The prevention and
      treatment of chronic diseases is now rising on global policy agendas, highlighted
      by the UN Summit on Noncommunicable Diseases (September 2011). Briefs and
      declarations leading up to this Summit reference the role of globalization and
      trade in the spread of risk factors for these diseases, but emphasis is placed on
      interventions to change health behaviours and on voluntary corporate
      responsibility. The findings summarized in this article imply the need for a more
      concerted approach to regulate trade-related risk factors and thus more
      engagement between health and trade policy sectors within and between nations. An
      explicit recognition of the role of trade policies in the spread of
      noncommunicable disease risk factors should be a minimum outcome of the September
      2011 Summit, with a commitment to ensure that future trade treaties do not
      increase such risks.

PMID- 21726435
TI  - A comprehensive introduction to the genetic basis of non-syndromic hearing loss
      in the Saudi Arabian population.
AB  - BACKGROUND: Hearing loss is a clinically and genetically heterogeneous disorder.
      Mutations in the DFNB1 locus have been reported to be the most common cause of
      autosomal recessive non-syndromic hearing loss worldwide. Apart from DFNB1, many
      other loci and their underlying genes have also been identified and the basis of
      our study was to provide a comprehensive introduction to the delineation of the
      molecular basis of non-syndromic hearing loss in the Saudi Arabian population.
      This was performed by screening DFNB1 and to initiate prioritized linkage
      analysis or homozygosity mapping for a pilot number of families in which DFNB1
      has been excluded. METHODS: Individuals from 130 families of Saudi Arabian tribal
      origin diagnosed with an autosomal recessive non-syndromic sensorineural hearing
      loss were screened for mutations at the DFNB1 locus by direct sequencing. If
      negative, genome wide linkage analysis or homozygosity mapping were performed
      using Affymetrix GeneChip(r) Human Mapping 250K/6.0 Arrays to identify regions
      containing any known-deafness causing genes that were subsequently sequenced.
      RESULTS: Our results strongly indicate that DFNB1 only accounts for 3% of non
      syndromic hearing loss in the Saudi Arabian population of ethnic ancestry.
      Prioritized linkage analysis or homozygosity mapping in five separate families
      established that their hearing loss was caused by five different known-deafness
      causing genes thus confirming the genetic heterogeneity of this disorder in the
      kingdom. CONCLUSION: The overall results of this study are highly suggestive that
      underlying molecular basis of autosomal recessive non-syndromic deafness in Saudi
      Arabia is very genetically heterogeneous. In addition, we report that the
      preliminary results indicate that there does not seem to be any common or more
      prevalent loci, genes or mutations in patients with autosomal recessive non
      syndromic hearing loss in patients of Saudi Arabian tribal origin.

PMID- 21726436
TI  - Nano-electrospray tandem mass spectrometric analysis of the acetylation state of
      histones H3 and H4 in stationary phase in Saccharomyces cerevisiae.
AB  - BACKGROUND: The involvement of histone acetylation in facilitating gene
      expression is well-established, particularly in the case of histones H3 and H4.
      It was previously shown in Saccharomyces cerevisiae that gene expression was
      significantly down-regulated and chromatin more condensed in stationary phase
      compared to exponential phase. We were therefore interested in establishing the
      acetylation state of histone H3 and H4 in stationary and in exponential phase,
      since the regulation of this modification could contribute to transcriptional
      shut-down and chromatin compaction during semi-quiescence. RESULTS: We made use
      of nano-spray tandem mass spectrometry to perform a precursor ion scan to detect
      an m/z 126 immonium ion, diagnostic of an Nepsilon-acetylated lysine residue that
      allowed unambiguous identification of acetylated as opposed to tri-methylated
      lysine. The fragmentation spectra of peptides thus identified were searched with
      Mascot against the Swiss-Prot database, and the y-ion and b-ion fragmentation
      series subsequently analyzed for mass shifts compatible with acetylated lysine
      residues. We found that K9, K14 and K36 of histone H3 and K12 and K16 of histone
      H4 were acetylated in exponential phase (bulk histones), but could not detect
      these modifications in histones isolated from stationary phase cells at the
      sensitivity level of the mass spectrometer. The corresponding un-acetylated
      peptides were, however, observed. A significantly higher level of acetylation of
      these residues in exponential phase was confirmed by immuno-blotting. CONCLUSION:
      H4K16 acetylation was previously shown to disrupt formation of condensed
      chromatin in vitro. We propose that de-acetylation of H4K16 allowed formation of
      condensed chromatin in stationary phase, and that acetylation of H3K9, H3K14,
      H3K36, and H4K12 reflected the active transcriptional state of the yeast genome
      in exponential phase.

PMID- 21726437
TI  - Loss of density-dependence and incomplete control by dominant breeders in a
      territorial species with density outbreaks.
AB  - BACKGROUND: A territory as a prerequisite for breeding limits the maximum number
      of breeders in a given area, and thus lowers the proportion of breeders if
      population size increases. However, some territorially breeding animals can have
      dramatic density fluctuations and little is known about the change from density
      dependent processes to density-independence of breeding during a population
      increase or an outbreak. We suggest that territoriality, breeding suppression and
      its break-down can be understood with an incomplete-control model, developed for
      social breeders and social suppression. RESULTS: We studied density dependence in
      an arvicoline species, the bank vole, known as a territorial breeder with cyclic
      and non-cyclic density fluctuations and periodically high densities in different
      parts of its range. Our long-term data base from 38 experimental populations in
      large enclosures in boreal grassland confirms that breeding rates are density
      regulated at moderate densities, probably by social suppression of subordinate
      potential breeders. We conducted an experiment, were we doubled and tripled this
      moderate density under otherwise the same conditions and measured space use,
      mortality, reproduction and faecal stress hormone levels (FGM) of adult females.
      We found that mortality did not differ among the densities, but the regulation of
      the breeding rate broke down: at double and triple densities all females were
      breeding, while at the low density the breeding rate was regulated as observed
      before. Spatial overlap among females increased with density, while a minimum
      territory size was maintained. Mean stress hormone levels were higher in double
      and triple densities than at moderate density. CONCLUSIONS: At low and moderate
      densities, breeding suppression by the dominant breeders, But above a density
      threshold (similar to a competition point), the dominance of breeders could not
      be sustained (incomplete control). In our experiment, this point was reached
      after territories could not shrink any further, while the number of intruders
      continued to increase with increasing density. Probably suppression becomes too
      costly for the dominants, and increasing number of other breeders reduces the
      effectiveness of threats. In wild populations, crossing this threshold would
      allow for a rapid density increase or population outbreaks, enabling territorial
      species to escape density-dependency.

PMID- 21726438
TI  - Colonization of Phlebotomus papatasi changes the effect of pre-immunization with
      saliva from lack of protection towards protection against experimental challenge
      with Leishmania major and saliva.
AB  - BACKGROUND: Sand fly saliva has been postulated as a potential vaccine or as a
      vaccine component within multi component vaccine against leishmaniasis. It is
      important to note that these studies were performed using long-term colonized
      Phlebotomus papatasi. The effect of sand flies colonization on the outcome of
      Leishmania infection is reported. RESULTS: While pre-immunization of mice with
      salivary gland homogenate (SGH) of long-term colonized (F5 and beyond) female
      Phlebotomus papatasi induced protection against Leishmania major co-inoculated
      with the same type of SGH, pre-immunization of mice with SGH of recently
      colonized (F2 and F3) female P. papatasi did not confer protection against L.
      major co-inoculated with the same type of SGH. Our data showed for the first time
      that a shift from lack of protection to protection occurs at the fourth
      generation (F4) during the colonization process of P. papatasi. CONCLUSION: For
      the development of a sand fly saliva-based vaccine, inferences based on long-term
      colonized populations of sand flies should be treated with caution as
      colonization of P. papatasi appears to modulate the outcome of L. major infection
      from lack of protection to protection.

PMID- 21726439
TI  - Development and validation of a short version of the Assessment of Chronic
      Illness Care (ACIC) in Dutch disease management programs.
AB  - BACKGROUND: In the Netherlands the extent to which chronically ill patients
      receive care congruent with the Chronic Care Model is unknown. The main
      objectives of this study were to (1) validate the Assessment of Chronic Illness
      Care (ACIC) in the Netherlands in various Disease Management Programmes (DMPs)
      and (2) shorten the 34-item ACIC while maintaining adequate validity,
      reliability, and sensitivity to change. METHODS: The Dutch version of the ACIC
      was tested in 22 DMPs with 218 professionals. We tested the instrument by means
      of structural equation modelling, and examined its validity, reliability and
      sensitivity to change. RESULTS: After eliminating 13 items, the confirmatory
      factor analyses revealed good indices of fit with the resulting 21-item ACIC
      (ACIC-S). Internal consistency as represented by Cronbach's alpha ranged from
      'acceptable' for the 'clinical information systems' subscale to 'excellent' for
      the 'organization of the healthcare delivery system' subscale. Correlations
      between the ACIC and ACIC-S subscales were also good, ranging from .87 to 1.00,
      indicating acceptable coverage of the core areas of the CCM. The seven subscales
      were significantly and positively correlated, indicating that the subscales were
      conceptually related but also distinct. Paired t-tests results show that the ACIC
      scores of the original instrument all improved significantly over time in regions
      that were in the process of implementing DMPs (all components at p < 0.0001).
      CONCLUSION: We conclude that the psychometric properties of the ACIC and the ACIC
      S are good and the ACIC-S is a promising alternate instrument to assess chronic
      illness care.

PMID- 21726440
TI  - The serious mental illness health improvement profile [HIP]: study protocol for a
      cluster randomised controlled trial.
AB  - BACKGROUND: The serious mental illness Health Improvement Profile [HIP] is a
      brief pragmatic tool, which enables mental health nurses to work together with
      patients to screen physical health and take evidence-based action when variables
      are identified to be at risk. Piloting has demonstrated clinical utility and
      acceptability. METHODS/DESIGN: A single blind parallel group cluster randomised
      controlled trial with secondary economic analysis and process observation. Unit
      of randomisation: mental health nurses [MHNs] working in adult community mental
      health teams across two NHS Trusts. SUBJECTS: Patients over 18 years with a
      diagnosis of schizophrenia, schizoaffective or bipolar disorder on the caseload
      of participating MHNs. PRIMARY OBJECTIVE: To determine the effects of the HIP
      programme on patients' physical wellbeing assessed by the physical component
      score of the Medical Outcome Study (MOS) 36 Item Short Form Health Survey version
      2 [SF-36v2]. SECONDARY OBJECTIVES: To determine the effects of the HIP programme
      on: cost effectiveness, mental wellbeing, cardiovascular risk, physical health
      care attitudes and knowledge of MHNs and to determine the acceptability of the
      HIP Programme in the NHS. Consented nurses (and patients) will be randomised to
      receive the HIP Programme or treatment as usual. Outcomes will be measured at
      baseline and 12 months with a process observation after 12 months to include
      evaluation of patients' and professionals' experience and observation of any
      effect on care plans and primary-secondary care interface communication. Outcomes
      will be analysed on an intention-to-treat (ITT) basis. DISCUSSION: The results of
      the trial and process observation will provide information about the
      effectiveness of the HIP Programme in supporting MHNs to address physical
      comorbidity in serious mental illness. Given the current unacceptable prevalence
      of physical comorbidity and mortality in the serious mental illness population,
      it is hoped the HIP trial will provide a timely contribution to evidence on
      organisation and delivery of care for patients, clinicians and policy makers.
      TRIAL REGISTRATION:  ISRCTN: ISRCTN41137900.

PMID- 21726441
TI  - "Fighting the system": families caring for ventilator-dependent children and
      adults with complex health care needs at home.
AB  - BACKGROUND: An increasing number of individuals with complex health care needs
      now receive life-long and life-prolonging ventilatory support at home. Family
      members often take on the role of primary caregivers. The aim of this study was
      to explore the experiences of families giving advanced care to family members
      dependent on home mechanical ventilation. METHODS: Using qualitative research
      methods, a Grounded Theory influenced approach was used to explore the families'
      experiences. A total of 15 family members with 11 ventilator-dependent
      individuals (three children and eight adults) were recruited for 10 in-depth
      interviews. RESULTS: The core category, "fighting the system," became the central
      theme as family members were asked to describe their experiences. In addition, we
      identified three subcategories, "lack of competence and continuity", "being
      indispensable" and "worth fighting for". This study revealed no major differences
      in the families' experiences that were dependent on whether the ventilator
      dependent individual was a child or an adult. CONCLUSIONS: These findings show
      that there is a large gap between family members' expectations and what the
      community health care services are able to provide, even when almost unlimited
      resources are available. A number of measures are needed to reduce the burden on
      these family members and to make hospital care at home possible. In the future,
      the gap between what the health care can potentially provide and what they can
      provide in real life will rapidly increase. New proposals to limit the extremely
      costly provision of home mechanical ventilation in Norway will trigger new
      ethical dilemmas that should be studied further.

PMID- 21726442
TI  - 1.5 Decades Later: Bearing fruits from the ACR/EULAR exchange Program.

PMID- 21726443
TI  - Is the Beck Anxiety Inventory a good tool to assess the severity of anxiety? A
      primary care study in the Netherlands Study of Depression and Anxiety (NESDA).
AB  - BACKGROUND: Appropriate management of anxiety disorders in primary care requires
      clinical assessment and monitoring of the severity of the anxiety. This study
      focuses on the Beck Anxiety Inventory (BAI) as a severity indicator for anxiety
      in primary care patients with different anxiety disorders (social phobia, panic
      disorder with or without agoraphobia, agoraphobia or generalized anxiety
      disorder), depressive disorders or no disorder (controls). METHODS: Participants
      were 1601 primary care patients participating in the Netherlands Study of
      Depression and Anxiety (NESDA). Regression analyses were used to compare the mean
      BAI scores of the different diagnostic groups and to correct for age and gender.
      RESULTS: Patients with any anxiety disorder had a significantly higher mean score
      than the controls. A significantly higher score was found for patients with panic
      disorder and agoraphobia compared to patients with agoraphobia only or social
      phobia only. BAI scores in patients with an anxiety disorder with a co-morbid
      anxiety disorder and in patients with an anxiety disorder with a co-morbid
      depressive disorder were significantly higher than BAI scores in patients with an
      anxiety disorder alone or patients with a depressive disorder alone. Depressed
      and anxious patients did not differ significantly in their mean scores.
      CONCLUSIONS: The results suggest that the BAI may be used as a severity indicator
      of anxiety in primary care patients with different anxiety disorders. However,
      because the instrument seems to reflect the severity of depression as well, it is
      not a suitable instrument to discriminate between anxiety and depression in a
      primary care population.

PMID- 21726444
TI  - Molecular characterization and phylogenetic study of peste des petits ruminants
      viruses from north central states of Nigeria.
AB  - BACKGROUND: Peste des petits ruminants is an endemic disease of sheep and goats
      in Nigeria and vaccination has been the method of control but sporadic outbreaks
      have been reported. This study was carried out to characterize PPR viruses from
      outbreaks in 2007 and 2009 from Kaduna and Plateau States. RESULTS: Of the 33
      clinical samples analysed, 51.52% (n = 17) were positive for F protein gene
      primers (F1/F2). All the samples had a sequence similarity of 98-100% among them
      and 92-97% with the reference vaccine (Nig 75/1) strain. The deduced amino acid
      homology ranges between 96.3-99.7%. Phylogenetically all the Nigerian sequences
      cluster with Nig 75/1 and Nig 76/1 in lineage 1. CONCLUSIONS: PPR is still a
      problem in Kaduna and Plateau States of Nigeria. The strains involved were
      genetically closely related to the vaccine strain (Nig 75/1) used in the country.
      Based on this study, the continued outbreaks in the Country is not due to the
      efficacy of the vaccine. Therefore, to achieve effective control and possibly
      eradication of PPR in Nigeria, the current control strategies should be
      revisited.

PMID- 21726445
TI  - A randomised controlled trial of extended brief intervention for alcohol
      dependent patients in an acute hospital setting (ADPAC).
AB  - BACKGROUND: Alcohol dependence affects approximately 3% of the English
      population, and accounts for significant medical and psychiatric morbidity. Only
      5.6% of alcohol-dependent individuals ever access specialist treatment and only a
      small percentage ever seek treatment. As people who are alcohol dependent are
      more likely to have experienced health problems leading to frequent attendance at
      acute hospitals it would seem both sensible and practical to ensure that this
      setting is utilised as a major access point for treatment, and to test the
      effectiveness of these treatments. METHODS/DESIGN: This is a randomised
      controlled trial with a primary hypothesis that extended brief interventions
      (EBI) delivered to alcohol-dependent patients in a hospital setting by an Alcohol
      Specialist Nurse (ASN) will be effective when compared to usual care in reducing
      overall alcohol consumption and improving on the standard measures of alcohol
      dependence. Consecutive patients will be screened for alcohol misuse in the
      Emergency Department (ED) of a district general hospital. On identification of an
      alcohol-related problem, following informed written consent, we aim to randomize
      130 patients per group. The ASN will discharge to usual clinical care all control
      group patients, and plan a programme of EBI for treatment group patients. Follow
      up interview will be undertaken by a researcher blinded to the intervention at 12
      and 24 weeks. The primary outcome measure is level of alcohol dependence as
      determined by the Severity of Alcohol Dependence Questionnaire (SADQ) score.
      Secondary outcome measures include; Alcohol Use Disorders Identification Test
      (AUDIT) score, quantity and frequency of alcohol consumption, health-related
      quality of life measures, service utilisation, and patient experience. The trial
      will also allow an assessment of the cost-effectiveness of EBI in an acute
      hospital setting. In addition, patient experience will be assessed using
      qualitative methods. DISCUSSION: This paper presents a protocol for a RCT of EBI
      delivered to alcohol dependent patients by an ASN within an ED. Importantly; the
      trial will also seek to understand patients' perceptions and experiences of being
      part of a RCT and of receiving this form of intervention. TRIAL REGISTRATION
      NUMBER: ISRCTN: ISRCTN78062794.

PMID- 21726446
TI  - Self-reported health status and access to health services in a sample of
      prisoners in Italy.
AB  - BACKGROUND: Self-reported health status in underserved population of prisoners
      has not been extensively explored. The purposes of this cross-sectional study
      were to assess self-reported health, quality of life, and access to health
      services in a sample of male prisoners of Italy. METHODS: A total of 908
      prisoners received a self-administered anonymous questionnaire pertaining on
      demographic and detention characteristics, self-reported health status and
      quality of life, access to health services, lifestyles, and participation to
      preventive, social, and rehabilitation programs. A total of 650 prisoners agreed
      to participate in the study and returned the questionnaire. RESULTS:
      Respectively, 31.6% and 43.5% of prisoners reported a poor perceived health
      status and a poor quality of life, and 60% admitted that their health was
      worsened or greatly worsened during the prison stay. Older age, lower education,
      psychiatric disorders, self-reported health problems on prison entry, and suicide
      attempts within prison were significantly associated with a perceived worse
      health status. At the time of the questionnaire delivery, 30% of the prisoners
      self-reported a health problem present on prison entry and 82% present at the
      time of the survey. Most frequently reported health problems included dental
      health problems, arthritis or joint pain, eye problems, gastrointestinal
      diseases, emotional problems, and high blood pressure. On average, prisoners
      encountered general practitioners six times during the previous year, and the
      frequency of medical encounters was significantly associated with older age,
      sentenced prisoners, psychiatric disorders, and self-reported health problems on
      prison entry. CONCLUSIONS: The findings suggest that prisoners have a perceived
      poor health status, specific care needs and health promotion programs are seldom
      offered. Programs for correction of risk behaviour and prevention of long-term
      effects of incarceration on prisoners' health are strongly needed.

PMID- 21726447
TI  - Detection of lineage-specific evolutionary changes among primate species.
AB  - BACKGROUND: Comparison of the human genome with other primates offers the
      opportunity to detect evolutionary events that created the diverse phenotypes
      among the primate species. Because the primate genomes are highly similar to one
      another, methods developed for analysis of more divergent species do not always
      detect signs of evolutionary selection. RESULTS: We have developed a new method,
      called DivE, specifically designed to find regions that have evolved either more
      or less rapidly than expected, for any clade within a set of very closely related
      species. Unlike some previous methods, DivE does not rely on rates of synonymous
      and nonsynonymous substitution, which enables it to detect evolutionary events in
      noncoding regions. We demonstrate using simulated data that DivE compares
      favorably to alternative methods, and we then apply DivE to the ENCODE regions in
      14 primate species. We identify thousands of regions in these primates, ranging
      from 50 to >10000 bp in length, that appear to have experienced either
      constrained or accelerated rates of evolution. In particular, we detected 4942
      regions that have potentially undergone positive selection in one or more primate
      species. Most of these regions occur outside of protein-coding genes, although we
      identified 20 proteins that have experienced positive selection. CONCLUSIONS:
      DivE provides an easy-to-use method to predict both positive and negative
      selection in noncoding DNA, that is particularly well-suited to detecting lineage
      specific selection in large genomes.

PMID- 21726448
TI  - Efficacy of tension-free vaginal tape compared with transobturator tape in the
      treatment of stress urinary incontinence in women: analysis of learning curve,
      perioperative changes of voiding function.
AB  - BACKGROUND: In this study, by comparing TVT surgery and TOT surgery for stress
      urinary incontinence in women, the characteristics and learning curves of both
      operative methods were studied. METHODS: A total of 83 women with stress urinary
      incontinence treated with tension-free vaginal tape (TVT) (n = 38) or
      transobturator tape (TOT) (n = 45) at Saiseikai Central Hospital between April
      2004 and September 2009 were included. We compare the outcomes and learning
      curves between TVT surgery and TOT surgery. In statistical analysis, Student's t
      test, Fisher's exact test, and Mann-Whitney's U test were used. RESULTS: The
      surgical durations were 37.4 +/- 15.7 minutes with TVT surgery and 31.0 +/- 8.3
      minutes with TOT surgery. A longer period of time was required for TVT surgery (p
      = 0.025). The residual urine at post-operative day 1 was higher in TVT surgery
      (25.9 +/- 44.2 ml) than in TOT surgery (10.6 +/- 19.2 ml) (p = 0.0452). The
      surgical duration of TVT surgery was shortened after the operator had performed
      15 operations (p = 0.019). CONCLUSIONS: In comparison of TVT surgery and TOT
      surgery, the surgical duration of TVT surgery was longer and the residual urine
      of TVT surgery was higher at post-operative day 1. Surgical experience could
      shorten the duration of TVT surgery.

PMID- 21726449
TI  - Matrix metalloproteinases and their inhibitors in canine mammary tumors.
AB  - BACKGROUND: Malignant canine mammary tumors represent 50% of all neoplasms in
      female dogs. Matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) are thought to be involved in tumor progression, and
      they are also associated with the reactive stroma, which provides structural and
      vascular support for tumor growth. RESULTS: MMP-2, MMP-9 and MT1-MMP were
      expressed at both the mRNA and protein levels in tumor samples. MMP-2 and MMP-9
      immunohistochemical reactions were evident both in the epithelial tumor cells and
      in the stromal compartment to varying degrees; in particular, the intensity of
      the MMP-2 staining was stronger in the stromal fibroblasts close to epithelial
      tumor cells in simple carcinomas than in adenomas. These data were supported by
      gelatin-zymography; bands for the active form of MMP-2 were found in 94% of
      carcinoma samples, compared with 17% of benign tumor samples. The gene expression
      and immunohistochemical results for MT1-MMP were comparable to those for MMP-2.
      The immunoreactivity for MMP-13 and TIMP-2 was lower in carcinomas than in
      adenomas, confirming the mRNA data for MMP-13 and the other MMP inhibitors that
      were evaluated. The active form of MMP-9, but not the active form of MMP-2, was
      identified in the plasma of all of the tested dogs. CONCLUSIONS: Our findings
      suggest that MMP-9, MMP-2 and MT1-MMP, which are synthesized by epithelial cancer
      cells and cancer-associated fibroblasts, play an important role in malignant
      canine mammary tumors. The reduction of MMP-13 and TIMP-2 could also be a
      significant step in malignant transformation. MMP-2 and MT1-MMP could be further
      evaluated as future biomarkers for predicting the progression and prognosis of
      canine mammary tumors.

PMID- 21726450
TI  - Contrast-enhanced CMR in patients after percutaneous closure of the left atrial
      appendage: a pilot study.
AB  - BACKGROUND: To evaluate the feasibility and value of first-pass contrast-enhanced
      dynamic and post-contrast 3D CMR in patients after transcatheter occlusion of
      left atrial appendage (LAA) to identify incorrect placement and persistent leaks.
      METHODS: 7 patients with different occluder systems (n = 4 PLAATO; n = 2
      Watchman; n = 1 ACP) underwent 2 contrast-enhanced (Gd-DOTA) CMR sequences (2D
      TrueFISP first-pass perfusion and 3D-TurboFLASH) to assess localization, artifact
      size and potential leaks of the devices. Perfusion CMR was analyzed visually and
      semi-quantitatively to identify potential leaks. RESULTS: All occluders were
      positioned within the LAA. The ACP occluder presented the most extensive artifact
      size. Visual assessment revealed a residual perfusion of the LAA apex in 4 cases
      using first-pass perfusion and 3D-TurboFLASH indicating a suboptimal LAA
      occlusion.By assessing signal-to-time-curves the cases with a visually detected
      leak showed a 9-fold higher signal-peak in the LAA apex (567 +/- 120% increase
      from baseline signal) than those without a leak (61 +/- 22%; p < 0.03). In
      contrast, the signal increase in LAA proximal to the occluder showed no
      difference (leak 481 +/- 201% vs. no leak 478 +/- 125%; p = 0.48). CONCLUSION:
      This CMR pilot study provides valuable non-invasive information in patients after
      transcatheter occlusion of the LAA to identify correct placement and potential
      leaks. We recommend incorporating CMR in future clinical studies to evaluate new
      device types.

PMID- 21726451
TI  - Immunogenicity of autoantigens.
AB  - BACKGROUND: Autoantibodies against self-antigens have been associated not only
      with autoimmune diseases, but also with cancer and are even found in healthy
      individuals. The mechanism causing the autoantibody response remains elusive for
      the majority of the immunogenic antigens. To deepen the understanding of
      autoantibody responses, we ask whether natural-occurring, autoimmunity-associated
      and tumor-associated antigens have structural or biological features related to
      the immune response. To this end, we have carried out the most comprehensive in
      silicio study of different groups of autoantigens including large antigen sets
      identified by our groups combined with publicly available antigen sets. RESULTS:
      We found evidence for an enrichment of genes with a larger exon length increasing
      the probability of the occurrence of potential immunogenic features such as
      mutations, SNPs, immunogenic sequence patterns and structural epitopes, or
      alternative splicing events. While SNPs seem to play a more central role in
      autoimmunity, somatic mutations seem to be stronger enriched in tumor-associated
      antigens. In addition, antigens of autoimmune diseases are different from other
      antigen sets in that they appear preferentially secreted, have frequently an
      extracellular location, and they are enriched in pathways associated with the
      immune system. Furthermore, for autoantibodies in general, we found enrichment of
      sequence-based properties including coiled-coils motifs, ELR motifs, and Zinc
      finger DNA-binding motifs. Moreover, we found enrichment of proteins binding to
      proteins or nucleic acids including RNA and enrichment of proteins that are part
      of ribosome or spliceosome. Both, homologies to proteins of other species and an
      enrichment of ancient protein domains indicate that immunogenic proteins are
      evolutionary conserved and that mimicry might play a central role. CONCLUSIONS:
      Our results provide evidence that proteins which i) are evolutionary conserved,
      ii) show specific sequence motifs, and iii) are part of cellular structures show
      an increased likelihood to become autoimmunogenic.

PMID- 21726452
TI  - Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with
      CoVaccine HTTM and Montanide ISA 51 in rhesus macaques.
AB  - BACKGROUND: Increasing the breadth of the functional antibody response through
      immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1) multi
      allele vaccine formulations has been demonstrated in several rodent and rabbit
      studies. This study assesses the safety and immunogenicity of three PfAMA1
      Diversity-Covering (DiCo) vaccine candidates formulated as an equimolar mixture
      (DiCo mix) in CoVaccine HTTM or Montanide ISA 51, as well as that of a PfAMA1
      MSP119 fusion protein formulated in Montanide ISA 51. METHODS: Vaccine safety in
      rhesus macaques was monitored by animal behaviour observation and assessment of
      organ and systemic functions through clinical chemistry and haematology
      measurements. The immunogenicity of vaccine formulations was assessed by enzyme
      linked immunosorbent assays and in vitro parasite growth inhibition assays with
      three culture-adapted P. falciparum strains. RESULTS: These data show that both
      adjuvants were well tolerated with only transient changes in a few of the
      chemical and haematological parameters measured. DiCo mix formulated in CoVaccine
      HTTM proved immunologically and functionally superior to the same candidate
      formulated in Montanide ISA 51. Immunological data from the fusion protein
      candidate was however difficult to interpret as four out of six immunized animals
      were non-responsive for unknown reasons. CONCLUSIONS: The study highlights the
      safety and immunological benefits of DiCo mix as a potential human vaccine
      against blood stage malaria, especially when formulated in CoVaccine HTTM, and
      adds to the accumulating data on the specificity broadening effects of DiCo mix.

PMID- 21726453
TI  - Two-color fluorescent in situ hybridization in the embryonic zebrafish brain
      using differential detection systems.
AB  - BACKGROUND: Whole-mount in situ hybridization (WISH) is extensively used to
      characterize gene expression patterns in developing and adult brain and other
      tissues. To obtain an idea whether a novel gene might be involved in
      specification of a distinct brain subdivision, nucleus or neuronal lineage, it is
      often useful to correlate its expression with that of a known regional or
      neuronal marker gene. Two-color fluorescent in situ hybridization (FISH) can be
      used to compare different transcript distributions at cellular resolution.
      Conventional two-color FISH protocols require two separate rounds of horseradish
      peroxidase (POD)-based transcript detection, which involves tyramide signal
      amplification (TSA) and inactivation of the first applied antibody-enzyme
      conjugate before the second detection round. RESULTS: We show here that the
      alkaline phosphatase (AP) substrates Fast Red and Fast Blue can be used for
      chromogenic as well as fluorescent visualization of transcripts. To achieve high
      signal intensities we optimized embryo permeabilization properties by hydrogen
      peroxide treatment and hybridization conditions by application of the viscosity
      increasing polymer dextran sulfate. The obtained signal enhancement allowed us to
      develop a sensitive two-color FISH protocol by combining AP and POD reporter
      systems. We show that the combination of AP-Fast Blue and POD-TSA
      carboxyfluorescein (FAM) detection provides a powerful tool for simultaneous
      fluorescent visualization of two different transcripts in the zebrafish brain.
      The application of different detection systems allowed for a one-step antibody
      detection procedure for visualization of transcripts, which significantly reduced
      working steps and hands-on time shortening the protocol by one day. Inactivation
      of the first applied reporter enzyme became unnecessary, so that false-positive
      detection of co-localization by insufficient inactivation, a problem of
      conventional two-color FISH, could be eliminated. CONCLUSION: Since POD activity
      is rather quickly quenched by substrate excess, less abundant transcripts can
      often not be efficiently visualized even when applying TSA. The use of AP-Fast
      Blue fluorescent detection may provide a helpful alternative for fluorescent
      transcript visualization, as the AP reaction can proceed for extended times with
      a high signal-to-noise ratio. Our protocol thus provides a novel alternative for
      comparison of two different gene expression patterns in the embryonic zebrafish
      brain at a cellular level. The principles of our method were developed for use in
      zebrafish but may be easily included in whole-mount FISH protocols of other model
      organisms.

PMID- 21726454
TI  - Perspectives on key principles of generalist medical practice in public service
      in sub-Saharan Africa: a qualitative study.
AB  - BACKGROUND: The principles and practice of Family Medicine that arose in
      developed Western countries have been imported and adopted in African countries
      without adequate consideration of their relevance and appropriateness to the
      African context. In this study we attempted to elicit a priori principles of
      generalist medical practice from the experience of long-serving medical officers
      in a variety of African counties, through which we explored emergent principles
      of Family Medicine in our own context. METHODS: A descriptive study design was
      utilized, using qualitative methods. 16 respondents who were clinically active
      medical practitioners, working as generalists in the public services or non
      profit sector for at least 5 years, and who had had no previous formal training
      or involvement in academic Family Medicine, were purposively selected in 8
      different countries in southern, western and east Africa, and interviewed.
      RESULTS: The respondents highlighted a number of key issues with respect to the
      external environment within which they work, their collective roles, activities
      and behaviours, as well as the personal values and beliefs that motivate their
      behaviour. The context is characterized by resource constraints, high workload,
      traditional health beliefs, and the difficulty of referring patients to the next
      level of care. Generalist clinicians in sub-Saharan Africa need to be competent
      across a wide range of clinical disciplines and procedural skills at the level of
      the district hospital and clinic, in both chronic and emergency care. They need
      to understand the patient's perspective and context, empowering the patient and
      building an effective doctor-patient relationship. They are also managers,
      focused on coordinating and improving the quality of clinical care through
      teamwork, training and mentoring other health workers in the generalist setting,
      while being life-long learners themselves. However, their role in the community,
      was found to be more aspirational than real. CONCLUSIONS: The study derived a set
      of principles for the practice of generalist doctors in sub-Saharan Africa based
      on the reported activities and approaches of the respondents. Patient-centred
      care using a biopsychosocial approach remains as a common core principle despite
      wide variations in context. Procedural and hospital care demands a higher level
      of skills particularly in rural areas, and a community orientation is desirable,
      but not widely practiced. The results have implications for the postgraduate
      training of family physicians in sub-Saharan Africa, and highlight questions
      regarding the realization of community-orientated primary care.

PMID- 21726455
TI  - Characterization of the age-dependent intervertebral disc changes in rabbit by
      correlation between MRI, histology and gene expression.
AB  - BACKGROUND: The present study was conducted to address whether the intervertebral
      disc of rabbit could be considered (i) as a valuable model to provide new
      insights into the tissue and cellular changes of Nucleus pulposus aging and (ii)
      as an appropriate tool to investigate the efficacy of Nucleus pulposus cell-based
      biotherapies. METHODS: Lumbar intervertebral disc from rabbits with increasing
      ages (1, 6 and 30 month-old) were compared by MRI and histological observation
      using Pfirrmann's grading and Boos' scoring respectively. The expression of
      transcripts (COL2A1, AGC1, COL1A1, MMP13, BMP2, MGP and p21) in Nucleus pulposus
      cells were analysed by quantitative real-time PCR. RESULTS: MRI analysis
      indicated an early age-dependent increase in the Pfirrmann's grading.
      Histological Boos' scoring was also increased. The analysis of transcript
      expression levels showed that COL2A1 and AGC1 were down-regulated as a function
      of age. Conversely, COL1A1, MMP-13, BMP-2, MGP and p21 were significantly up
      regulated in the Nucleus pulposus cells of aged rabbit intervertebral disc.
      CONCLUSIONS: Our study describes the consistency of the rabbit as a model of
      intervertebral disc changes as a function of age by correlating tissue alteration
      with cellular modification measured.

PMID- 21726456
TI  - Predator-induced changes of female mating preferences: innate and experiential
      effects.
AB  - BACKGROUND: In many species males face a higher predation risk than females
      because males display elaborate traits that evolved under sexual selection, which
      may attract not only females but also predators. Females are, therefore,
      predicted to avoid such conspicuous males under predation risk. The present study
      was designed to investigate predator-induced changes of female mating preferences
      in Atlantic mollies (Poecilia mexicana). Males of this species show a pronounced
      polymorphism in body size and coloration, and females prefer large, colorful
      males in the absence of predators. RESULTS: In dichotomous choice tests predator
      naive (lab-reared) females altered their initial preference for larger males in
      the presence of the cichlid Cichlasoma salvini, a natural predator of P.
      mexicana, and preferred small males instead. This effect was considerably weaker
      when females were confronted visually with the non-piscivorous cichlid Vieja
      bifasciata or the introduced non-piscivorous Nile tilapia (Oreochromis
      niloticus). In contrast, predator experienced (wild-caught) females did not
      respond to the same extent to the presence of a predator, most likely due to a
      learned ability to evaluate their predators' motivation to prey. CONCLUSIONS: Our
      study highlights that (a) predatory fish can have a profound influence on the
      expression of mating preferences of their prey (thus potentially affecting the
      strength of sexual selection), and females may alter their mate choice behavior
      strategically to reduce their own exposure to predators. (b) Prey species can
      evolve visual predator recognition mechanisms and alter their mate choice only
      when a natural predator is present. (c) Finally, experiential effects can play an
      important role, and prey species may learn to evaluate the motivational state of
      their predators.

PMID- 21726457
TI  - A cross-sectional assessment of population demographics, HIV risks and human
      rights contexts among men who have sex with men in Lesotho.
AB  - BACKGROUND: Evidence is increasing of high HIV risks among southern African men
      who have sex with men (MSM). This represents the first study of HIV risks and
      human rights contexts among MSM in Lesotho. METHODS: Two hundred and fifty-two
      men who reported ever having anal sex with another man were accrued with snowball
      sampling and were administered a structured quantitative instrument in October
      and November 2009. RESULTS: Of the participants, 96.4% (240/249) were ethnic
      Basotho with a mean age of 26.3 years (range 18-56), 49.6% (124/250) were
      currently employed, and 95.2% (238/250) had at least a secondary-level education.
      Self-reported HIV prevalence was 11.6% (22/190); 54.5% (128/235) reported being
      tested for HIV in the last year. HIV knowledge was low; only 3.7% (8/212) of MSM
      knew that receptive anal intercourse was the highest risk for HIV and that a
      water-based lubricant was most appropriate to use with condoms.Bivariate
      associations of wearing condoms during last intercourse with men include: having
      easy access to condoms (OR 3.1, 95% CI 1.2-8.5, p < 0.05); being older than 26
      years (OR 2.3, 95% CI 1.3-4.2, p < 0.01); knowing that receptive anal intercourse
      is higher risk than insertive anal intercourse (OR 2.6, 95% CI 1.2-5.9, p <
      0.05); wearing condoms with female sexual partners (OR 3.5, 95% 1.4-8.3, p <
      0.01); using water-based lubricants (OR 2.8, 95% CI 1.4-5.5, p < 0.01); being
      less likely to report having been diagnosed with a sexually transmitted infecton
      (OR 0.21, 95% CI 0.06-0.76, p < 0.05); and being more likely to have been tested
      for HIV in the last year (OR 2.0, 95% CI 1.2-3.6, p > 0.05).Human rights abuses
      were common: 76.2% (170/223) reported at least one abuse, including rape (9.8%,
      22/225), blackmail (21.3%, 47/221), fear of seeking healthcare (22.2%, 49/221),
      police discrimination (16.4%, 36/219), verbal or physical harassment (59.8%,
      140/234), or having been beaten (18.9%, 43/228). CONCLUSIONS: MSM in Lesotho are
      at high risk for HIV infection and human rights abuses. Evidence-based and rights
      affirming HIV prevention programmes supporting the needs of MSM should be
      developed and implemented.

PMID- 21726458
TI  - Severe isolated thrombocytopenia after clopidogrel and pentoxifylline therapy: a
      case report.
AB  - INTRODUCTION: Clopidogrel is frequently associated with thrombotic
      thrombocytopenic purpura, however this drug is rarely related to severe isolated
      thrombocytopenia. Pentoxifylline has previously been associated with
      thrombocytopenia only once. To the best of our knowledge, this is the first
      report of severe isolated thrombocytopenia after therapy with both clopidogrel
      and pentoxyfilline. CASE PRESENTATION: We report the case of a 79-year-old
      Caucasian man who presented to our facility with intermittent claudication. He
      had obliterative arterial disease and started therapy with clopidogrel and
      pentoxifylline. His basal platelet count was 194 * 109 cells/L. At three days
      after the start of treatment, our patient had lower limb petechia and stopped
      taking clopidogrel and pentoxifylline. His platelet count lowered to 4 * 109
      cells/L and our patient was admitted to hospital. Our patient had purpura with no
      other hemorrhages or splenomegaly. Results of a blood smear were normal, and a
      bone marrow study showed dysmegakaryopoiesis. Antiplatelet antibody test results
      were negative, as were all viral serology tests. Imaging study results were
      normal. Our patient was given immunoglobulin but there was no sustained platelet
      increase, so corticotherapy was started as the next treatment step. At five
      months after clopidogrel and pentoxifylline were discontinued, his platelet count
      continued increasing even after prednisolone was tapered. CONCLUSIONS: Severe
      isolated thrombocytopenia may appear as a side effect when using clopidogrel and
      pentoxifylline. These drugs are widely used by general physicians, internists,
      cardiologists and vascular surgeons. We hope this report will raise awareness of
      the need to monitor the platelet count in patients taking these drugs.

PMID- 21726459
TI  - Phylogeographic divergence in the widespread delicate skink (Lampropholis
      delicata) corresponds to dry habitat barriers in eastern Australia.
AB  - BACKGROUND: The mesic habitats of eastern Australia harbour a highly diverse
      fauna. We examined the impact of climatic oscillations and recognised
      biogeographic barriers on the evolutionary history of the delicate skink
      (Lampropholis delicata), a species that occurs in moist habitats throughout
      eastern Australia. The delicate skink is a common and widespread species whose
      distribution spans 26 degrees  of latitude and nine major biogeographic barriers
      in eastern Australia. Sequence data were obtained from four mitochondrial genes
      (ND2, ND4, 12SrRNA, 16SrRNA) for 238 individuals from 120 populations across the
      entire native distribution of the species. The evolutionary history and
      diversification of the delicate skink was investigated using a range of
      phylogenetic (Maximum Likelihood, Bayesian) and phylogeographic analyses (genetic
      diversity, PhiST, AMOVA, Tajima's D, Fu's F statistic). RESULTS: Nine
      geographically structured, genetically divergent clades were identified within
      the delicate skink. The main clades diverged during the late Miocene-Pliocene,
      coinciding with the decline and fragmentation of rainforest and other wet forest
      habitats in eastern Australia. Most of the phylogeographic breaks within the
      delicate skink were concordant with dry habitat or high elevation barriers,
      including several recognised biogeographic barriers in eastern Australia
      (Burdekin Gap, St Lawrence Gap, McPherson Range, Hunter Valley, southern New
      South Wales). Genetically divergent populations were also located in high
      elevation topographic isolates inland from the main range of L. delicata
      (Kroombit Tops, Blackdown Tablelands, Coolah Tops). The species colonised South
      Australia from southern New South Wales via an inland route, possibly along the
      Murray River system. There is evidence for recent expansion of the species range
      across eastern Victoria and into Tasmania, via the Bassian Isthmus, during the
      late Pleistocene. CONCLUSIONS: The delicate skink is a single widespread, but
      genetically variable, species. This study provides the first detailed
      phylogeographic investigation of a widespread species whose distribution spans
      virtually all of the major biogeographic barriers in eastern Australia.

PMID- 21726460
TI  - Low-molecular-weight heparin reduces hyperoxia-augmented ventilator-induced lung
      injury via serine/threonine kinase-protein kinase B.
AB  - BACKGROUND: High-tidal-volume mechanical ventilation and hyperoxia used in
      patients with acute lung injury (ALI) can induce the release of cytokines,
      including high-mobility group box-1 (HMGB1), oxygen radicals, neutrophil
      infiltration, and the disruption of epithelial and endothelial barriers.
      Hyperoxia has been shown to increase ventilator-induced lung injury, but the
      mechanisms regulating interaction between high tidal volume and hyperoxia are
      unclear. We hypothesized that subcutaneous injections of enoxaparin would
      decrease the effects of hyperoxia on high-tidal-volume ventilation-induced HMGB1
      production and neutrophil infiltration via the serine/threonine kinase/protein
      kinase B (Akt) pathway. METHODS: Male C57BL/6, either wild type or Akt+/-, aged
      between 6 and 8 weeks, weighing between 20 and 25 g, were exposed to high-tidal
      volume (30 ml/kg) mechanical ventilation with room air or hyperoxia for 2 to 8
      hours with or without 4 mg/kg enoxaparin administration. Nonventilated mice
      served as a control group. Evan blue dye, lung wet-to-dry weight ratio, free
      radicals, myeloperoxidase, Western blot of Akt, and gene expression of HMGB1 were
      measured. The expression of HMGB1 was studied by immunohistochemistry. RESULTS:
      High-tidal-volume ventilation using hyperoxia induced microvascular permeability,
      Akt activation, HMGB1 mRNA expression, neutrophil infiltration, oxygen radicals,
      HMGB1 production, and positive staining of Akt in bronchial epithelium. Hyperoxia
      induced augmentation of ventilator-induced lung injury was attenuated with Akt
      deficient mice and pharmacological inhibition of Akt activity by enoxaparin.
      CONCLUSION: These data suggest that enoxaparin attenuates hyperoxia-augmented
      high-tidal-volume ventilation-induced neutrophil influx and HMGB1 production
      through inhibition of the Akt pathway. Understanding the protective mechanism of
      enoxaparin related with the reduction of HMGB1 may help further knowledge of the
      effects of mechanical forces in the lung and development of possible therapeutic
      strategies involved in acute lung injury.

PMID- 21726461
TI  - Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the
      interleukin-1beta gene in healthy adults.
AB  - BACKGROUND: Recently, hypothalamus-pituitary-adrenal (HPA) axis function assessed
      with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test
      has been shown to be associated with response to antidepressant treatment. A
      polymorphism (rs16944) in the interleukin-1beta (IL-1beta) gene has also been
      reported to be associated with the medication response in depression. These
      findings prompted us to examine the possible association between IL-1beta gene
      polymorphisms and HPA axis function assessed with the DEX/CRH test. METHODS:
      DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 +/-
      15.8 years; 134 females: mean age 47.1 +/- 13.2 years). Five tagging single
      nucleotide polymorphisms (SNPs) of IL-1beta gene (rs2853550, rs1143634,
      rs1143633, rs1143630, rs16944) were selected at an r2 threshold of 0.80 with a
      minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic
      discrimination assay. A two-way factorial analysis of variance (ANOVA) was
      performed with the DEX/CRH test results as the dependent variable and genotype
      and gender as independent variables. To account for multiple testing, P values <
      0.01 were considered statistically significant for associations between the
      genotypes and the cortisol levels. RESULTS: The cortisol levels after DEX
      administration (DST-Cortisol) showed significant associations with the genotypes
      of rs16944 (P = 0.00049) and rs1143633 (P = 0.0060), with no significant gender
      effect or genotype * gender interaction. On the other hand, cortisol levels after
      CRH administration (DEX/CRH-Cortisol) were affected by gender but were not
      significantly influenced by the genotype of the examined SNPs, with no
      significant genotype * gender interaction. CONCLUSIONS: Our results suggest that
      genetic variations in the IL-1beta gene contribute to the HPA axis alteration
      assessed by DST-Cortisol in healthy subjects. On the other hand, no significant
      associations of the IL-1beta gene polymorphisms with the DEX/CRH-Cortisol were
      observed. Confirmation of our findings in futures studies may add new insight
      into the communication between the immune system and the HPA axis.

PMID- 21726462
TI  - Matrix-assisted laser desorption/ionisation mass spectrometry imaging and its
      development for plant protein imaging.
AB  - Matrix-Assisted Laser Desorption/Ionisation (MALDI) mass spectrometry imaging
      (MSI) uses the power of high mass resolution time of flight (ToF) mass
      spectrometry coupled to the raster of lasers shots across the cut surface of
      tissues to provide new insights into the spatial distribution of biomolecules
      within biological tissues. The history of this technique in animals and plants is
      considered and the potential for analysis of proteins by this technique in plants
      is discussed. Protein biomarker identification from MALDI-MSI is a challenge and
      a number of different approaches to address this bottleneck are discussed. The
      technical considerations needed for MALDI-MSI are reviewed and these are
      presented alongside examples from our own work and a protocol for MALDI-MSI of
      proteins in plant samples.

PMID- 21726463
TI  - EXACT: exercise or advice after ankle fracture. Design of a randomised controlled
      trial.
AB  - BACKGROUND: Ankle fractures are common. Management of ankle fractures generally
      involves a period of immobilisation followed by rehabilitation to reduce pain,
      stiffness, weakness and swelling. The effects of a rehabilitation program are
      still unclear. However, it has been shown that important components of
      rehabilitation programs may not confer additional benefits over exercise alone.
      The primary aim of this trial is to determine the effectiveness and cost
      effectiveness of an exercise-based rehabilitation program after ankle fracture,
      compared to advice alone. METHODS/DESIGN: A pragmatic randomised trial will be
      conducted. Participants will be 342 adults with stiff, painful ankles after ankle
      fracture treated with immobilisation. They will be randomly allocated using a
      concealed randomisation procedure to either an Advice or Rehabilitation group.
      Participants in the Advice group will receive verbal and written advice about
      exercise at the time of removal of immobilisation. Participants in the
      Rehabilitation group will be provided with a 4-week rehabilitation program that
      is designed, monitored and progressed by a physiotherapist, in addition to verbal
      and written advice. Outcomes will be measured by a blinded assessor at 1, 3 and 6
      months. The primary outcomes will be activity limitation and quality-adjusted
      life years. DISCUSSION: This pragmatic trial will determine if a rehabilitation
      program reduces activity limitation and improves quality of life, compared to
      advice alone, after immobilisation for ankle fracture.

PMID- 21726464
TI  - Chronic kidney disease of unknown aetiology in Sri Lanka: is cadmium a likely
      cause?
AB  - BACKGROUND: The rising prevalence of chronic kidney disease (CKD) and subsequent
      end stage renal failure necessitating renal replacement therapy has profound
      consequences for affected individuals and health care resources. This community
      based study was conducted to identify potential predictors of microalbuminuria in
      a randomly selected sample of adults from the North Central Province (NCP) of Sri
      Lanka, where the burden of CKD is pronounced and the underlying cause still
      unknown. METHODS: Exposures to possible risk factors were determined in randomly
      recruited subjects (425 females and 461 males) from selected areas of the NCP of
      Sri Lanka using an interviewer administered questionnaire. Sulphosalicylic acid
      and the Light Dependent Resister microalbumin gel filtration method was used for
      initial screening for microalbuminuria and reconfirmed by the Micral strip test.
      RESULTS: Microalbumnuria was detected in 6.1% of the females and 8.5% of the
      males. Smoking (p < 0.001), alcohol use (p = 0.003), hypertension (p < 0.001),
      diabetes (p < 0.001), urinary tract infection (UTI) (p = 0.034) and consumption
      of water from wells in the fields (p = 0.025) were associated with
      microalbuminuria. In the binary logistic regression analysis, hypertension,
      diabetes mellitus, UTI, drinking well water in the fields, smoking and pesticide
      spraying were found to be significant predictors of microalbuminuria.
      CONCLUSIONS: Hypertension, diabetes mellitus, UTI, and smoking are known risk
      factors for microalbuminuria. The association between microalbuminuria and
      consumption of well water suggests an environmental aetiology to CKD in NCP. The
      causative agent is yet to be identified. Investigations for cadmium as a
      potential causative agent needs to be initiated.

PMID- 21726466
TI  - Generation of polyclonal antibody with high avidity to rosuvastatin and its use
      in development of highly sensitive ELISA for determination of rosuvastatin in
      plasma.
AB  - In this study, a polyclonal antibody with high avidity and specificity to the
      potent hypocholesterolaemic agent rosuvastatin (ROS) has been prepared and used
      in the development of highly sensitive enzyme-linked immunosorbent assay (ELISA)
      for determination of ROS in plasma. ROS was coupled to keyhole limpt hemocyanin
      (KLH) and bovine serum albumin (BSA) using carbodiimide reagent. ROS-KLH
      conjugate was used for immunization of female 8-weeks old New Zealand white
      rabbits. The immune response of the rabbits was monitored by direct ELISA using
      ROS-BSA immobilized onto microwell plates as a solid phase. The rabbit that
      showed the highest antibody titer and avidity to ROS was scarified and its sera
      were collected. The IgG fraction was isolated and purified by avidity
      chromatography on protein A column. The purified antibody showed high avidity to
      ROS; IC50 = 0.4 ng/ml. The specificity of the antibody for ROS was evaluated by
      indirect ELISA using various competitors from the ROS-structural analogues and
      the therapeutic agents used with ROS in a combination therapy. The proposed ELISA
      involved a competitive binding reaction between ROS, in plasma sample, and the
      immobilized ROS-BSA for the binding sites on a limited amount of the anti-ROS
      antibody. The bound anti-ROS antibody was quantified with horseradish peroxidase
      labeled second anti-rabbit IgG antibody (HRP-IgG) and 3,3',5,5'
      tetramethylbenzidine (TMB) as a substrate for the peroxidase enzyme. The
      concentration of ROS in the sample was quantified by its ability to inhibit the
      binding of the anti-ROS antibody to the immobilized ROS-BSA and subsequently the
      color intensity in the assay wells. The assay enabled the determination of ROS in
      plasma at concentrations as low as 40 pg/ml.

PMID- 21726465
TI  - Modulation of growth and angiogenic potential of oral squamous carcinoma cells in
      vitro using salvianolic acid B.
AB  - BACKGROUND: Our previous studies showed that Salvianolic acid B (Sal B) inhibited
      7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and
      such anti-cancer effects might be related to the inhibition of angiogenesis. This
      study was aimed to further investigate the anti-proliferative effect of Sal B on
      the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the
      possible mechanisms of action with respect to angiogenesis inhibition. METHODS:
      Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4,
      and premalignant leukoplakia cells were treated with different concentrations of
      Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to
      evaluate the expression of 96 genes known to be involved in modulating the
      biological processes of angiogenesis. Real-time reverse transcription-polymerase
      chain reaction analysis was conducted to confirm the cDNA microarray data.
      RESULTS: Sal B induced growth inhibition in OSCC cell lines but had limited
      effects on premalignant cells. A total of 17 genes showed a greater than 3-fold
      change when comparing Sal B treated OSCC cells to the control. Among these genes,
      HIF-1alpha, TNFalpha and MMP9 are specifically inhibited, expression of THBS2 was
      up-regulated. CONCLUSIONS: Sal B has inhibitory effect on OSCC cell growth. The
      antitumor effect can be attributed to anti-angiogenic potential induced by a
      decreased expression of some key regulator genes of angiogenesis. Sal B may be a
      promising modality for treating oral squamous cell carcinoma.

PMID- 21726467
TI  - 'Pregnancy comes accidentally--like it did with me': reproductive decisions among
      women on ART and their partners in rural Uganda.
AB  - BACKGROUND: As highly active antiretroviral therapy (ART) restores health,
      fertility and sexual activity among HIV-infected adults, understanding how ART
      influences reproductive desires and decisions could inform interventions to
      reduce sexual and vertical HIV transmission risk. METHODS: We performed a
      qualitative sub-study among a Ugandan cohort of 1,000 adults on ART with four
      purposively selected categories of participants: pregnant, not pregnant,
      delivered, and aborted. In-depth interviews examined relationships between HIV,
      ART and pregnancy, desire for children, perceived risks and benefits of
      pregnancy, decision-making regarding reproduction and family planning (FP) among
      29 women and 16 male partners. Analysis focused on dominant explanations for
      emerging themes across and within participant groups. RESULTS: Among those who
      had conceived, most couples stated that their pregnancy was unintentional, and
      often occurred because they believed that they were infertile due to HIV.
      Perceived reasons for women not getting pregnant included: ill health (included
      HIV infection and ART), having enough children, financial constraints, fear of
      mother-to-child HIV transmission or transmission to partner, death of a child,
      and health education. Most women reported FP experiences with condoms and
      hormonal injections only. Men had limited FP information apart from condoms.
      CONCLUSIONS: Counselling at ART initiation may not be sufficient to enable women
      who do not desire children to adopt relevant family planning practices. On-going
      reproductive health education and FP services, with emphasis on the restoration
      of fertility after ART initiation, should be integrated into ART programs for men
      and women.

PMID- 21726468
TI  - Decrease of energy spilling in Escherichia coli continuous cultures with rising
      specific growth rate and carbon wasting.
AB  - BACKGROUND: Growth substrates, aerobic/anaerobic conditions, specific growth rate
      (MU) etc. strongly influence Escherichia coli cell physiology in terms of cell
      size, biomass composition, gene and protein expression. To understand the
      regulation behind these different phenotype properties, it is useful to know
      carbon flux patterns in the metabolic network which are generally calculated by
      metabolic flux analysis (MFA). However, rarely is biomass composition determined
      and carbon balance carefully measured in the same experiments which could
      possibly lead to distorted MFA results and questionable conclusions. Therefore,
      we carried out both detailed carbon balance and biomass composition analysis in
      the same experiments for more accurate quantitative analysis of metabolism and
      MFA. RESULTS: We applied advanced continuous cultivation methods (A-stat and D
      stat) to continuously monitor E. coli K-12 MG1655 flux and energy metabolism
      dynamic responses to change of MU and glucose-acetate co-utilisation.
      Surprisingly, a 36% reduction of ATP spilling was detected with increasing MU and
      carbon wasting to non-CO2 by-products under constant biomass yield. The apparent
      discrepancy between constant biomass yield and decline of ATP spilling could be
      explained by the rise of carbon wasting from 3 to 11% in the carbon balance which
      was revealed by the discovered novel excretion profile of E. coli pyrimidine
      pathway intermediates carbamoyl-phosphate, dihydroorotate and orotate. We found
      that carbon wasting patterns are dependent not only on MU, but also on glucose
      acetate co-utilisation capability. Accumulation of these compounds was coupled to
      the two-phase acetate accumulation profile. Acetate overflow was observed in
      parallel with the reduction of TCA cycle and glycolysis fluxes, and induction of
      pentose phosphate pathway. CONCLUSIONS: It can be concluded that acetate
      metabolism is one of the major regulating factors of central carbon metabolism.
      More importantly, our model calculations with actual biomass composition and
      detailed carbon balance analysis in steady state conditions with -omics data
      comparison demonstrate the importance of a comprehensive systems biology approach
      for more advanced understanding of metabolism and carbon re-routing mechanisms
      potentially leading to more successful metabolic engineering.

PMID- 21726469
TI  - Exploring the selective constraint on the sizes of insertions and deletions in 5'
      untranslated regions in mammals.
AB  - BACKGROUND: Small insertions and deletions ("indels" with size >/= 100 bp) whose
      lengths are not multiples of three (non-3n) are strongly constrained and depleted
      in protein-coding sequences. Such a constraint has never been reported in
      noncoding genomic regions. In 5'untranslated regions (5'UTRs) in mammalian
      genomes, upstream start codons (uAUGs) and upstream open reading frames (uORFs)
      can regulate protein translation. The presence of non-3n indels in uORFs can
      potentially disrupt the functions of these regulatory elements. We thus
      hypothesize that natural selection disfavors non-3n indels in 5'UTRs when these
      regulatory elements are present. RESULTS: We design the Indel Selection Index to
      measure the selective constraint on non-3n indels in 5'UTRs. The index controls
      for the genomic compositions of the analyzed 5'UTRs and measures the probability
      of non-3n indel depletion downstream of uAUGs. By comparing the experimentally
      supported transcripts of human-mouse orthologous genes, we demonstrate that non
      3n indels downstream of two types of uAUGs (alternative translation initiation
      sites and the uAUGs of coding sequence-overlapping uORFs) are underrepresented.
      The results hold well regardless of differences in alignment tool, gene
      structures between human and mouse, or the criteria in selecting alternatively
      spliced isoforms used for the analysis. CONCLUSIONS: To our knowledge, this is
      the first study to demonstrate selective constraints on non-3n indels in 5'UTRs.
      Such constraints may be associated with the regulatory functions of uAUGs/uORFs
      in translational regulation or the generation of protein isoforms. Our study thus
      brings a new perspective to the evolution of 5'UTRs in mammals.

PMID- 21726470
TI  - A computational procedure for functional characterization of potential marker
      genes from molecular data: Alzheimer's as a case study.
AB  - BACKGROUND: A molecular characterization of Alzheimer's Disease (AD) is the key
      to the identification of altered gene sets that lead to AD progression. We rely
      on the assumption that candidate marker genes for a given disease belong to
      specific pathogenic pathways, and we aim at unveiling those pathways stable
      across tissues, treatments and measurement systems. In this context, we analyzed
      three heterogeneous datasets, two microarray gene expression sets and one protein
      abundance set, applying a recently proposed feature selection method based on
      regularization. RESULTS: For each dataset we identified a signature that was
      successively evaluated both from the computational and functional
      characterization viewpoints, estimating the classification error and retrieving
      the most relevant biological knowledge from different repositories. Each
      signature includes genes already known to be related to AD and genes that are
      likely to be involved in the pathogenesis or in the disease progression. The
      integrated analysis revealed a meaningful overlap at the functional level.
      CONCLUSIONS: The identification of three gene signatures showing a relevant
      overlap of pathways and ontologies, increases the likelihood of finding potential
      marker genes for AD.

PMID- 21726471
TI  - Dementia.
AB  - INTRODUCTION: Dementia is characterised by chronic, global, non-reversible
      deterioration in memory, executive function, and personality. Speech and motor
      function may also be impaired. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical question: What are the effects
      of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or
      vascular)? What are the effects of treatments on behavioural and psychological
      symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to April 2008
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      33 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions:
      acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine),
      antidepressants (clomipramine, fluoxetine, imipramine, sertraline),
      antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy,
      benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT),
      cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers
      (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal
      anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and
      statins.

PMID- 21726472
TI  - Subarachnoid haemorrhage (spontaneous aneurysmal).
AB  - INTRODUCTION: Subarachnoid haemorrhage (SAH) may arise spontaneously or as a
      result of trauma. Spontaneous SAH accounts for about 5% of all strokes. Ruptured
      aneurysms are the cause of 85% of spontaneous SAH. The most characteristic
      clinical feature is sudden-onset severe headache. Other features include
      vomiting, photophobia, and focal neurological deficit or seizures, or both. As
      the headache may have insidious onset in some cases, or may even be absent, a
      high degree of suspicion is required to diagnose SAH with less typical
      presentations. METHODS AND OUTCOMES: We conducted a systematic review and aimed
      to answer the following clinical questions: What are the effects of surgical
      treatments for people with confirmed aneurysmal subarachnoid haemorrhage? What
      are the effects of medical treatments to prevent delayed cerebral ischaemia in
      people with confirmed aneurysmal subarachnoid haemorrhage? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to March 2009
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      6 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions:
      endovascular coiling; surgical clipping; timing of surgery; and oral and
      intravenous nimodipine.

PMID- 21726473
TI  - Genital prolapse in women.
AB  - INTRODUCTION: Prolapse of the uterus or vagina is usually the result of loss of
      pelvic support, and causes mainly non-specific symptoms. It may affect over half
      of women aged 50 to 59 years, but spontaneous regression may occur. Risks of
      genital prolapse increase with advancing parity and age, increasing weight of the
      largest baby delivered, and hysterectomy. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of non-surgical treatments in women with genital prolapse? What are
      the effects of surgical treatments in women with anterior vaginal wall prolapse?
      What are the effects of surgical treatments in women with posterior vaginal wall
      prolapse? What are the effects of surgical treatments in women with upper vaginal
      wall prolapse? What are the effects of using different surgical materials in
      women with genital prolapse? We searched: Medline, Embase, The Cochrane Library,
      and other important databases up to June 2009 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 14 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: abdominal Burch colposuspension; abdominal
      sacral colpopexy; abdominal sacrohysteropexy; anterior colporrhaphy with mesh
      reinforcement; laparoscopic surgery; mesh or synthetic grafts; native
      (autologous) tissue; open abdominal surgery; pelvic floor muscle exercises;
      posterior colporrhaphy (with or without mesh reinforcement); posterior
      intravaginal slingplasty (infracoccygeal sacropexy); sacrospinous colpopexy
      (vaginal sacral colpopexy); sutures; traditional anterior colporrhaphy; transanal
      repair; ultralateral anterior colporrhaphy alone or with cadaveric fascia patch;
      vaginal hysterectomy; vaginal oestrogen; vaginal pessaries; and vaginal
      sacrospinous colpopexy.

PMID- 21726474
TI  - Diabetes: treating hypertension.
AB  - INTRODUCTION: Among people with diabetes, about 40% of those aged 45 years, and
      more than 60% of those aged 75 years and over, will have a blood pressure over
      140/90 mmHg. Major cardiac events occur in approximately 5% of people with
      diabetes and untreated hypertension each year, and the risk is higher in those
      with other risk factors, such as diabetic nephropathy. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of antihypertensives in people with diabetes and
      hypertension? What are the effects of different blood pressure targets in people
      with diabetes and hypertension? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to February 2009 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 22
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. CONCLUSIONS: In this systematic review, we present information relating
      to the effectiveness and safety of the following interventions: alpha-blockers;
      angiotensin II receptor antagonists; angiotensin-converting enzyme (ACE)
      inhibitors; beta-blockers; blood pressure targets (lower or higher); calcium
      channel blockers; and diuretics.

PMID- 21726476
TI  - Tinnitus.
AB  - INTRODUCTION: Up to 18% of people in industrialised societies are mildly affected
      by chronic tinnitus, and 0.5% report tinnitus having a severe effect on their
      daily life. Tinnitus can be associated with hearing loss, acoustic neuromas, drug
      toxicity, ear diseases, and depression. Tinnitus can last for many years, and can
      interfere with sleep and concentration. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical question: What are
      the effects of treatments for chronic tinnitus? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to May 2009 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 27
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions:
      acamprosate; acupuncture; antidepressant drugs; benzodiazepines; carbamazepine;
      cinnarizine; electromagnetic stimulation; ginkgo biloba; hearing aids; hypnosis;
      psychotherapy; tinnitus-masking devices; and tinnitus retraining therapy.

PMID- 21726477
TI  - HIV: treating tuberculosis.
AB  - INTRODUCTION: In people infected with both HIV and Mycobacterium tuberculosis,
      the annual risk of developing active tuberculosis is 5% to 10% - more than 10
      times the rate for HIV-negative people with M tuberculosis infection. Untreated,
      mortality from tuberculosis in people with HIV is likely to be high, and over 5%
      of people relapse after successful treatment. METHODS AND OUTCOMES: We conducted
      a systematic review and aimed to answer the following clinical questions: What
      are the effects of first-line treatments for tuberculosis in HIV-positive people?
      What are the effects of second-line treatments for tuberculosis in HIV-positive
      people? We searched: Medline, Embase, The Cochrane Library, and other important
      databases up to July 2009 (Clinical Evidence reviews are updated periodically;
      please check our website for the most up-to-date version of this review). We
      included harms alerts from relevant organisations such as the US Food and Drug
      Administration (FDA) and the UK Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: We found 23 systematic reviews, RCTs, or observational
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review we
      present information relating to the effectiveness and safety of the following
      interventions: adjuvant immunotherapy (with corticosteroids, or Mycobacterium
      vaccae); antimycobacterial treatment combinations; conventional antituberculous
      treatment (short course, long course, including rifabutin [3 or 5 months],
      quinolones, or thiacetazone); directly observed therapy (short course); highly
      active antiretroviral treatment (early initiation or delayed initiation);
      rifampicin (3 months or less); secondary prophylaxis with antituberculous
      treatment; and unsupervised treatment.

PMID- 21726475
TI  - Hay fever in adolescents and adults.
AB  - INTRODUCTION: Hay fever is found throughout the world. Epidemiological evidence
      suggests considerable geographical variation in its prevalence. Symptoms are
      caused by an IgE-mediated type 1 hypersensitivity reaction to airborne allergens
      such as pollen or fungal spores, and may also cause eye, sinus, respiratory, and
      systemic problems. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical question: What are the effects of
      treatments for hay fever in adolescents and adults? We searched: Medline, Embase,
      The Cochrane Library, and other important databases up to April 2008 (Clinical
      Evidence reviews are updated periodically; please check our website for the most
      up-to-date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 211
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions:
      intranasal corticosteroids, oral antihistamines, intranasal antihistamines, oral
      leukotriene receptor antagonists, systemic corticosteroids, intranasal
      ipratropium bromide, oral decongestants, and combinations of these treatments.

PMID- 21726478
TI  - Warts (non-genital).
AB  - INTRODUCTION: Warts are caused by the human papillomavirus (HPV), of which there
      are over 100 types, which probably infects the skin via areas of minimal trauma.
      Risk factors include use of communal showers, occupational handling of meat, and
      immunosuppression. In immunocompetent people, warts are harmless and resolve as a
      result of natural immunity within months or years. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      question: What are the effects of treatments for warts (non-genital)? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to June 2008 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 12 systematic reviews, RCTs, or observational studies that met
      our inclusion criteria. We performed a GRADE evaluation of the quality of
      evidence for interventions. CONCLUSIONS: In this systematic, review we present
      information relating to the effectiveness and safety of the following
      interventions: intralesional bleomycin; cimetidine; contact immunotherapy;
      cryotherapy; duct tape occlusion; formaldehyde, glutaraldehyde; homeopathy;
      photodynamic treatment; pulsed dye laser; surgical procedures; topical salicylic
      acid; and zinc sulphate.

PMID- 21726479
TI  - Hepatitis B (prevention).
AB  - INTRODUCTION: Nearly a third of the world's population has been infected by
      hepatitis B at some point, and at least 350 million people have become chronic
      carriers. Progressive liver damage occurs in up to 25% of carriers. In areas of
      high endemicity, transmission occurs largely in childhood; from an infected
      mother to her baby, or between members of a household. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of vaccination against hepatitis B infection in
      countries with high endemicity? What are the effects of vaccination against
      hepatitis B infection in countries with low endemicity? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to June 2008
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations, such as the US Food and Drug Administration (FDA), and
      the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We
      found 51 systematic reviews, RCTs, or observational studies that met our
      inclusion criteria. We performed a GRADE evaluation of the quality of evidence
      for interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions:
      selective vaccination of high-risk individuals; selective vaccination of people
      with chronic liver disease not caused by hepatitis B; universal vaccination of
      adolescents; and universal vaccination of infants.

PMID- 21726480
TI  - Amblyopia.
AB  - INTRODUCTION: Amblyopia is commonly associated with squint (strabismus) or
      refractive errors resulting in different visual inputs to each eye during the
      sensitive period of visual development (<7-8 years of age). The cumulative
      incidence is estimated at 2% to 4% in children aged up to 15 years. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of interventions to detect amblyopia
      early? What are the effects of medical treatments for amblyopia? We searched:
      Medline, Embase, The Cochrane Library, and other important databases up to May
      2008 (Clinical Evidence reviews are updated periodically; please check our
      website for the most up-to-date version of this review). We included harms alerts
      from relevant organisations, such as the US Food and Drug Administration (FDA)
      and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS:
      We found 16 systematic reviews, RCTs, or observational studies that met our
      inclusion criteria. We performed a GRADE evaluation of the quality of evidence
      for interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions: active
      vision therapy; glasses alone or with occlusion; or penalisation to treat
      amblyopia; and screening to detect amblyopia early.

PMID- 21726481
TI  - Gastroenteritis in children.
AB  - INTRODUCTION: Acute gastroenteritis results from infection of the
      gastrointestinal tract, most commonly with a virus. It is characterised by rapid
      onset of diarrhoea with or without vomiting, nausea, fever, and abdominal pain.
      Diarrhoea is defined as the frequent passage of unformed, liquid stools.
      Regardless of the cause, the mainstay of management of acute gastroenteritis is
      provision of adequate fluids to prevent and treat dehydration. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of interventions to prevent acute
      gastroenteritis in children? What are the effects of treatments for acute
      gastroenteritis in children? We searched: Medline, Embase, The Cochrane Library,
      and other important databases up to August 2007 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 20 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of: rotavirus vaccines for the prevention of gastroenteritis; enteral
      rehydration solutions (oral or gastric), lactose-free feeds, and loperamide for
      the treatment of gastroenteritis; and ondansetron for the treatment of vomiting.

PMID- 21726482
TI  - Herpes labialis.
AB  - INTRODUCTION: Herpes simplex virus type 1 infection usually causes a mild, self
      limiting painful blistering around the mouth, with 20% to 40% of adults affected
      at some time. Primary infection usually occurs in childhood, after which the
      virus is thought to remain latent in the trigeminal ganglion. Recurrence may be
      triggered by factors such as exposure to bright light, stress, and fatigue.
      METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the
      following clinical questions: What are the effects of antiviral treatments for
      the first attack of herpes labialis? What are the effects of interventions aimed
      at preventing recurrent attacks of herpes labialis? What are the effects of
      treatments for recurrent attacks of herpes labialis? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to February 2009
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      27 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: oral
      antiviral agents, sunscreen, topical anaesthetic agents, topical antiviral
      agents, and zinc oxide cream.

PMID- 21726483
TI  - Hip fracture.
AB  - INTRODUCTION: Between 12% and 37% of people will die in the year after a hip
      fracture, and 10% to 20% of survivors will move into a more dependent residence.
      METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the
      following clinical questions: What are the effects of surgical interventions in
      people with hip fracture? What are the effects of perisurgical medical
      interventions on surgical outcome and prevention of complications in people with
      hip fracture? What are the effects of rehabilitation interventions and programmes
      after hip fracture? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to April 2009 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 55 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: anaesthesia (general, regional); antibiotic
      regimens; arthroplasty; choice of implant for internal fixation; conservative
      treatment; co-ordinated multidisciplinary approaches for inpatient rehabilitation
      of older people; cyclical compression of the foot or calf; early supported
      discharge followed by home-based rehabilitation; extramedullary devices; fixation
      (external, internal); graduated elastic compression; intramedullary devices;
      mobilisation strategies; nerve blocks for pain control; nutritional
      supplementation (oral multinutrient feeds, nasogastric feeds); perioperative
      prophylaxis with antibiotics, with antiplatelet agents, or with heparin (low
      molecular weight or unfractionated); preoperative traction to the injured limb;
      and systematic multicomponent home-based rehabilitation.

PMID- 21726484
TI  - Sleep apnoea.
AB  - INTRODUCTION: Sleep apnoea is the popular term for obstructive sleep apnoea
      hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes
      recurrent arousals, sleep fragmentation, excessive daytime sleepiness, and
      nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of
      inspiratory effort, or "obstructive", in which inspiratory efforts continue but
      are ineffective because of upper airway obstruction. OSAHS affects up to 4% of
      men and 2% of women in the USA, with obesity being a major determinant. METHODS
      AND OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of treatment for severe obstructive
      sleep apnoea-hypopnoea syndrome? What are the effects of treatment for non-severe
      obstructive sleep apnoea-hypopnoea syndrome? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to May 2008 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 43
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: nasal
      continuous positive airway pressure (CPAP); measures aimed at improving
      compliance with CPAP; oral appliances; and weight loss.

PMID- 21726485
TI  - Nausea and vomiting in early pregnancy.
AB  - INTRODUCTION: More than half of pregnant women suffer from nausea and vomiting,
      which typically begins by the 4th week and disappears by the 16th week of
      pregnancy. The cause of nausea and vomiting in pregnancy is unknown, but may be
      due to the rise in human chorionic gonadotrophin concentration. In 1 in 200
      women, the condition progresses to hyperemesis gravidarum, which is characterised
      by prolonged and severe nausea and vomiting, dehydration, and weight loss.
      METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the
      following clinical questions: What are the effects of treatment for nausea and
      vomiting in early pregnancy? What are the effects of treatments for hyperemesis
      gravidarum? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to May 2008 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 30 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: acupressure; acupuncture; antihistamines;
      corticosteroids; corticotrophins; diazepam; dietary interventions other than
      ginger; domperidone; ginger; metoclopramide; ondansetron; phenothiazines; and
      pyridoxine (vitamin B6).

PMID- 21726487
TI  - Primary prevention of CVD: physical activity.
AB  - INTRODUCTION: Increasing physical activity has been associated with reduced risk
      of mortality and of cardiovascular disease (CVD). The proportion of people doing
      no physical activity in a week varies between countries, but can reach nearly 25%
      in Europe and the Americas. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical questions: Does counselling
      people to increase physical activity lead to increased physical activity in
      healthy people without existing CVD? What are the health benefits of increasing
      physical activity in relation to cardiovascular outcomes in healthy people
      without existing CVD? We searched: Medline, Embase, The Cochrane Library, and
      other important databases up to September 2008 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 21 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: counselling people to increase physical
      activity, and to perform higher-intensity exercise programmes.

PMID- 21726486
TI  - Sids.
AB  - INTRODUCTION: By definition, the cause of sudden infant death syndrome (SIDS) is
      not known. Observational studies have found an association between SIDS and
      several risk factors, including prone sleeping position, prenatal or postnatal
      exposure to tobacco smoke, soft sleeping surfaces, hyperthermia/overwrapping, bed
      sharing (particularly with mothers who smoke), lack of breastfeeding, and lack of
      soother use. The risk of SIDS is increased in families in which there has been a
      prior sudden infant death. METHODS AND OUTCOMES: We conducted a systematic review
      and aimed to answer the following clinical question: What are the effects of
      interventions to reduce the risk of SIDS? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to April 2007 (Clinical
      Evidence reviews are updated periodically; please check our website for the most
      up-to-date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 28
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions: advice
      to avoid prone sleeping; advice to avoid tobacco-smoke exposure; advice to avoid
      soft sleeping surfaces; advice to avoid overheating or overwrapping; advice to
      avoid bed sharing; advice to breastfeed; advice to promote soother/pacifier use;
      and advice to promote room sharing (without bed sharing).

PMID- 21726488
TI  - Hodgkin's lymphoma.
AB  - INTRODUCTION: People with Hodgkin's lymphoma usually present with a lump in the
      neck or upper chest, but a quarter of people also have fever, sweating, weight
      loss, fatigue, and itch. Almost all people with localised disease can be cured,
      and, even among people with relapsed advanced disease, almost 80% survive event
      free for 4 years or more. METHODS AND OUTCOMES: We conducted a systematic review
      and aimed to answer the following clinical questions: What are the effects of:
      single-regimen chemotherapy treatments; combined chemotherapy and radiotherapy
      treatments compared with radiotherapy alone; and combined chemotherapy and
      radiotherapy treatments compared with the same chemotherapy agent alone, for
      first presentation stage I or II non-bulky disease? What are the effects of:
      specific combined chemotherapy and radiotherapy treatments versus each other; or
      different radiotherapy treatment strategies in stage I or II non-bulky disease?
      What are the effects of: single-regimen chemotherapy treatments; dose-intensified
      chemotherapy treatments; or combined chemotherapy plus radiotherapy treatments
      compared with chemotherapy alone, for first presentation stage II (bulky)
      disease, III, or IV disease? We searched: Medline, Embase, The Cochrane Library,
      and other important databases up to September 2008 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 40 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: ABVD (with or without radiotherapy); ABVPP
      plus radiotherapy; ChlVPP-EVA; COPP-ABVD plus radiotherapy; CVPP plus
      radiotherapy; EBVP plus radiotherapy; escalating-dose BEACOPP; extended-field
      radiotherapy; increased-dose regimens; involved-field radiotherapy; MOPP (with or
      without radiotherapy); MOPP-ABV plus radiotherapy; and VBM plus radiotherapy.

PMID- 21726489
TI  - Hypothyroidism (primary).
AB  - INTRODUCTION: Hypothyroidism is six times more common in women, affecting up to
      40/10,000 each year (compared with 6/10,000 men). METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of treatments for clinical (overt)
      hypothyroidism? What are the effects of treatments for subclinical
      hypothyroidism? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to September 2009 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found six systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: levothyroxine, and levothyroxine plus
      liothyronine.

PMID- 21726491
TI  - Effects of surgery and chronic disease states on the concentrations and phenotype
      distribution of alpha1-acid glycoprotein: studies in patients with breast cancer
      and patients with chronic inflammatory disease.
AB  - OBJECTIVE: Although the concentration of alpha1-acid glycoprotein (AGP) in serum
      increases under some conditions, the behavior of the individual genetic variants
      is not well understood. Therefore, we studied the relative changes in AGP
      variants pre- and postoperatively in patients with cancer and patients with
      chronic inflammatory disease states, as well as the distribution of AGP
      phenotypes in a Japanese population. METHODS: Serum samples were taken before and
      after surgery from 25 female patients with early breast cancer. Serum samples
      were also obtained from 134 patients with rheumatoid arthritis (RA) and 33 with
      systemic lupus erythematosus (SLE), and from 103 healthy subjects. The relative
      concentrations of the individual genetic variants in the serum samples were
      determined by isoelectric focusing after desialylation with neuraminidase.
      RESULTS: The postoperative AGP concentrations in patients with early breast
      cancer were 2-fold higher than before surgery. The relative concentrations of the
      F1 and S variants were significantly increased, whereas that of the A variant was
      not changed significantly. The relative concentrations of all the AGP variants in
      patients with RA and SLE were significantly higher than those in healthy
      subjects. The distribution of the AGP phenotypes did not differ significantly
      among the groups examined in this study. CONCLUSIONS: The F1/S variants of AGP,
      but not the A variant, were significantly increased after early breast cancer
      surgery, but all the variants were increased in patients with chronic
      inflammatory states such as RA and SLE. The distribution of the AGP phenotypes
      did not differ significantly among the disease groups studied.

PMID- 21726490
TI  - Serotonin at the level of the amygdala and orbitofrontal cortex modulates
      distinct aspects of positive emotion in primates.
AB  - Impaired top-down regulation of the amygdala, and its modulation by serotonin (5
      HT), is strongly implicated in the dysregulation of negative emotion that
      characterizes a number of affective disorders. However, the contribution of these
      mechanisms to the regulation of positive emotion is not well understood. This
      study investigated the role of 5-HT within the amygdala and the orbitofrontal
      cortex (OFC), on the expression of appetitive Pavlovian conditioned emotional
      responses and their reversal in a primate, the common marmoset. Its effects were
      compared to those of the amygdala itself. Having developed conditioned autonomic
      and behavioural responses to an appetitive cue prior to surgery, marmosets with
      excitotoxic amygdala lesions failed to display such conditioned autonomic arousal
      at retention, but still displayed intact cue-directed conditioned behaviours. In
      contrast, 5,7-DHT infusions into the amygdala, reducing extracellular 5-HT
      levels, selectively enhanced the expression of appetitive conditioned behaviour
      at retention. Similar infusions into the OFC, producing marked reductions in post
      mortem 5-HT tissue levels, had no overall effect on autonomic or behavioural
      responses, either at retention or during reversal learning, but caused an
      uncoupling of these responses, thereby fractionating emotional output. These data
      demonstrate the critical role of the amygdala in the expression of appetitive
      autonomic conditioning, and the region-selective contribution of 5-HT in the
      amygdala and OFC, respectively, to the expression of conditioned behaviour and
      the overall coordination of the emotional response. They provide insight into the
      neurochemical mechanisms underlying the regulation of positive emotional
      responses, advancing our understanding of the neural basis of pathologically
      dysregulated emotion. 

PMID- 21726492
TI  - In vitro kinetics of delivery of tobramycin and ofloxacin from osmotic hydro gel
      expanders.
AB  - OBJECTIVE: High-hydrophilic osmotic self-inflating hydro gel expanders are well
      accepted for implantation to achieve tissue expansion in defined parts of the
      body like skin, breast and orbital soft tissue. To prevent post-implantation
      infections effective antibiotic prophylaxis might be helpful. The suitability of
      this hydro gel consisting of a co-polymer of N-vinyl-pyrolidone and methyl
      methacrylate as a drug delivery system for antibiotics was investigated in a
      laboratory setting simulating the orbit in a newborn. METHODS: In a first setting
      the dry expanders were incubated in a 0.3% solution (5 ml) of tobramycin and
      ofloxacin for 24 h (n = 10 for each substance, adsorbing 2.4 ml of the 0.3%
      solution, i.e. 7,200 MUg antibiotic). Addressing the release of both antibiotics,
      the concentrations in 15 ml elution medium (0.9% sodium chloride, renewed after
      every sampling) were measured after 0.25, 1, 2, 6, 24, 48 and 72 h of elution. To
      simulate the clinical use in a second setting the expanders were dried after
      incubation in a 0.3% and 0.03% solution of tobramycin (n = 5 for each
      concentration) before measuring the release. RESULTS: The cumulative amount of
      tobramycin released after 72 h reached 7,157 MUg, i.e. 99% of the initially
      loaded antibiotic. The cumulatively released amount of ofloxacin was 5,505 MUg
      (76% of loading dose). Main fraction of release (about two thirds) was detected
      for both antibiotics for a elution period 0 - 24 h. In the periods 24 - 48 and 48
      - 72 h the released amount of tobramycin was significantly higher than for
      ofloxacin. The release from expander dried after loading tobramycin was
      comparable: The cumulatively released amount of 0.3% and 0.03% incubation
      solution was 99% and 79% of loading dose, respectively. CONCLUSIONS: The
      investigated hydro gel expanders soaked in antibiotic solution can store and
      further on release sufficient amounts of tobramycin or ofloxacin to produce
      antimicrobial effective concentrations in vitro in the surrounding environment
      according to the breakpoints reported by EUCAST [14]. This principle, when used
      in a clinical setting, might help to eliminate post-implantation infection, which
      is one of the major complications in clinical use.

PMID- 21726493
TI  - Factors influencing carbamazepine pharmacokinetics in children and adults:
      population pharmacokinetic analysis.
AB  - OBJECTIVE: The aim of the present study was to build population pharmacokinetic
      models for the clearance of carbamazepine (CBZ) in two separate populations of
      Serbian patients with epilepsy, children and adults. METHODS: Analysis was
      performed using 114 and 53 steady-state concentrations of CBZ collected from 98
      children and 53 adult epileptic patients, respectively. Mean values of total body
      weight and age were 31 +/- 13 kg and 8 +/- 3 years in the population of children,
      and 67 +/- 13 kg and 32 +/- 15 years in the population of adults. The one
      compartment model with first order elimination and without absorption was used
      from the PREDPP (Prediction for Observation Population Pharmacokinetics) library
      of NONMEM software. RESULTS: The derived final models of CBZ clearance were
      similar in the target populations. The most important factors which affected
      typical mean value of CBZ clearance in both populations studied were age of the
      patients and total daily dose; the CBZ clearance linearly followed increase of
      these factors. However, the influence of the patients' age was almost 3.4 times
      higher in the pediatric population than that in adults while the influence of
      total daily dose of CBZ is similar. On the other hand, final model in the adult
      population revealed also influence of concomitant therapy with phenobarbital
      (PB). The magnitude of this effect was +1.61 l h-1. The pharmacokinetic models
      obtained were validated in groups of 18 children and 13 adults with epilepsy.
      CONCLUSIONS: The derived models describe well CBZ clearance in terms of Serbian
      pediatric and adult epileptic patient characteristics, offering a basis for
      rational individualization of CBZ dosage regimens.

PMID- 21726494
TI  - Hyponatremia associated with selective serotonin reuptake inhibitors,
      mirtazapine, and venlafaxine in Korean patients with major depressive disorder.
AB  - OBJECTIVE: Several reports of hyponatremia associated with the use of
      antidepressants such as selective serotonin reuptake inhibitors (SSRIs) have been
      published. This study compared the incidence of hyponatremia associated with
      SSRIs to that associated with mirtazapine and with venlafaxine in patients with
      major depressive disorder (MDD). MATERIAL AND METHODS: This retrospective study
      examined MDD in patients treated with an antidepressant over at least 4 weeks.
      Using medical records of 93 patients treated with an SSRI (paroxetine,
      sertraline, escitalopram, and fluoxetine), 76 patients treated with mirtazapine,
      and 71 patients treated with venlafaxine, we analyzed demographic variables and
      changes in serum sodium levels (at baseline and Week 4). RESULTS: Eight SSRIs
      group patients (8.6%) and three venlafaxine group patients (4.2%) exhibited mild
      hyponatremia during the study period. The SSRIs group's serum sodium level
      decreased only slightly, but significantly during treatment; however serum sodium
      levels in the mirtazapine and venlafaxine groups did not change significantly.
      The risk of developing hyponatremia while on an SSRI was greater in elderly
      subjects (60 years and older). CONCLUSION: These results indicate that, among
      patients with MDD, SSRIs treatment may be associated with decreased serum sodium
      levels, and the elderly patients are at greater risk for hyponatremia. Further
      prospective studies would help clarify the relative risks of hyponatremia among
      various antidepressants.

PMID- 21726495
TI  - Pharmacokinetic-pharmacodynamic equivalence of three gliclazide formulations in
      healthy human male subjects.
AB  - AIMS: To find out the pharmacokinetic (PK) and pharmacodynamic (PD) parameters
      for assessing the bioequivalence of three marketed products. To study the
      relationship between the pharmacokinetics of gliclazide and pharmacodynamic
      effect in healthy male volunteers. METHODS: This was an open label, balanced,
      randomized, 3-treatment, 3-sequence, 3 period, single-dose, cross-over
      bioavailability study in which 18 healthy adults were randomized to receive
      gliclazide 80 mg with 7 days wash out between treatments. The drug was
      administered with 240 ml of 20% glucose solution after a 10 h overnight fasting.
      Pharmacokinetic parameters like t(max), C(max), AUC(0-t), AUC(0-infinity), AUC(0
      t) / AUC(0-infinity) and t(1/2) and pharmacodynamic parameters like maximum
      effect (minimum glucose level in the body, C(minglu)), time to minimum glucose
      level in the body (T(cminglu)) and partial AUC were calculated for all the
      products. RESULTS: The values for mean +/- SD for age, height and weight of the
      volunteers were 28.00 +/- 22.68, 165.78 +/- 5.56 and 56.78 +/- 13.37
      respectively. There were total 4 withdrawn subjects and 1 drop out. Within batch
      accuracy of the method were in the range of 95.5 - 101.7%, 99.1 - 106.1% and 96.2
      - 104.2% for three consecutive batches. The 90% CI for log transformed data of
      the PK and PD were within the acceptance range of 80.0 - 125.0%. CONCLUSIONS:
      This population PKPD analysis has characterized the relationship between the
      exposure to gliclazide and its hypoglycemic effect. The test products A & B
      compared to reference product R were bioequivalent on the basis of
      pharmacokinetic and pharmacodynamic parameters. Finally it is recommended that
      the more costly product R can be safely switched with less costly products i.e. A
      and B.

PMID- 21726496
TI  - Study investigating pharmacokinetic interaction between theophylline and
      roflumilast in healthy adults.
AB  - OBJECTIVE: To investigate whether a pharmacokinetic drug-drug interaction exists
      between theophylline (THEO), a CYP1A2 substrate with a narrow therapeutic index,
      and the concomitant substrate roflumilast (ROF), a novel selective PDE4 inhibitor
      partially metabolized by CYP1A2. MATERIALS AND METHODS: In an open-label, 2
      period, crossover study, Treatment A (oral ROF 500 MUg q.d. on Days 6 - 10 in
      addition to oral THEO 375 mg b.i.d. on Days 1 - 10) and treatment B (oral ROF 500
      MUg q.d. on Days 1 - 5) were administered consecutively in random order to each
      of 24 healthy adult subjects. Both periods were separated by a wash-out phase of
      at least 10 days. Plasma samples for pharmacokinetic evaluation (AUC, Cmax, t1/2,
      tmax) including percent peak-trough fluctuation (%PTF) of THEO were taken. Point
      estimates and the 90% confidence interval of the geometric mean ratios were
      calculated for AUC and Cmax and descriptive statistics for other pharmacokinetic
      parameters. RESULTS: Concomitant administration of ROF did not alter
      pharmacokinetics of THEO. With coadministered THEO, only steady-state total
      exposure to ROF (AUC) was increased by 28% whereas other pharmacokinetic
      parameters (t1/2, Cmax, tmax) of ROF and of the active metabolite roflumilast-N
      oxide (R-NO), its main contributor to the pharmacodynamic effects, remained
      unchanged. CONCLUSIONS: Neither ROF nor its main metabolite had any impact on the
      metabolism of the concomitant CYP1A2 substrate THEO in humans. Though co
      administration of THEO resulted in a minor increase (28%) in total ROF exposure,
      no safety or tolerability concerns and no altered total PDE4 inhibition of both
      ROF and R-NO, were observed.

PMID- 21726498
TI  - Silymarin as a potential novel addition to the limited anti-vitiligo weaponry: an
      untested hypothesis.

PMID- 21726497
TI  - Successful treatment of erlotinib-induced acute hepatitis and acute interstitial
      pneumonitis with high-dose corticosteroid: a case report and literature review.
AB  - Erlotinib, a kind of epidermal growth factor receptor tyrosine kinase inhibitor,
      is a target therapy and approved for the treatment of metastatic non-small cell
      lung cancer (NSCLC) and advanced pancreatic cancer. Among these EGFR-TKI agents,
      including gefitinib and erlotinib, the common dose-limiting toxicities are
      diarrhea, mucositis and skin rash (Acneform eruptions). In addition to the above
      adverse effects, infrequent but potentially fatal and lethal entity complications
      include acute interstitial lung disease (ILD) and acute hepatitis. The incidence
      of EGFR-TKI agents (gefitinib and erlotinib) induced acute hepatitis is rare and
      hepatotoxicity of EGFR-TKI agent was rarely discussed. The treatment of EGFR-TKI
      agents induced acute hepatitis remains uncertain and cessation medication is
      current policy. Here we reported a case of erlotinib induced interstitial
      pneumonitis and acute hepatitis with clinical appearance of hypoxemia and general
      weakness, treated with high dose pulse therapy and showed good recovery.

PMID- 21726499
TI  - Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters
      of two formulations of clindamycin.
AB  - OBJECTIVE: The purpose of this study was to compare the pharmacokinetic
      parameters and determine the bioequivalence of a generic formulation of
      clindamycin that is sold in the local markets in the Middle East (Clindox(r) 150
      mg capsule; test) with a reference formulation (Dalacin C(r) 150 mg capsule) in
      healthy adult male volunteers. METHODS: A single-dose, open-label, 2-period
      crossover study was conducted. Healthy male volunteers were randomly assigned to
      oral administration of a single treatment of the reference and test formulations.
      The same groups were given the alternate formulation. After dosing, serial blood
      samples were withdrawn for a period of 24 h. Serum harvested from the blood
      samples was analyzed for clindamycin by high performance liquid chromatography
      (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC(0
      infinity), AUC(0-t), C(max), K(e), tmax and t(1/2) were determined from the serum
      concentrations for both formulations (test and reference). The products were
      tested for bioequivalence after log-transformation of the data. RESULTS: 24
      healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range
      19 - 45 years); height, 175.8 (10.6) cm (range 159.0 - 192.0 cm); weight, 75.6
      (11.0) kg (range 58 - 101 kg); and body mass index, 24.4 (1.8) kg/m2 (range 21.3 
      28 kg/m2) were enrolled in and completed the study. The 13C NMR spectra for both
      Dalacin C(r) and Clindox(r) showed 18 distinct lines associated with the 18
      different carbon atoms. CONCLUSION: The statistical comparison suggested that
      Clindox(r) capsules are bioequivalent to Dalacin C(r) capsules. The 13C CPMAS
      results confirmed that the two drugs exhibit typical clindamycin spectra.

PMID- 21726500
TI  - Clinical neuropathology, vol. 30 - no. 4/2011.

PMID- 21726501
TI  - Neuropathological work-up of focal cortical dysplasias using the new ILAE
      consensus classification system - practical guideline article invited by the Euro
      CNS Research Committee.
AB  - FCDs are increasingly recognized in patients with drug-resistant epilepsies, and
      many patients benefit from tailored resection strategies. Yet, postsurgical
      seizure control cannot be sufficiently predicted and specification of FCD
      variants remains difficult during presurgical monitoring. The International
      League against Epilepsy (ILAE) has published a new consensus classification
      system for focal cortical dysplasias (FCDs). Based on a review of imaging data,
      electroclinical features and postsurgical seizure control correlation with
      neuropathological findings specify three clinico-pathological FCD subtypes: FCD
      Type I is characterized by aberrant radial (FCD Type Ia) or tangential lamination
      of the neocortex (FCD Type Ib) affecting one or multiple lobes. FCD Type II is
      characterized by cortical dyslamination and dysmorphic neurons without (Type IIa)
      or with balloon cells (Type IIb). It is important to note, that these types
      should not be associated with any other structural brain lesion (isolated FCD).
      In contrast, a new FCD Type III is introduced, which occurs in combination with
      hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD
      Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas
      FCD Type IIId can be diagnosed in association with other epileptogenic lesions
      obtained in early life (i.e., traumatic injury, ischemic injury or encephalitis).
      Histopathological features are very similar to those observed in FCD Type I, but
      likely present postnatal development and maturation failures acquired by the
      principal lesion. This first international consensus classification may encourage
      neuropathologists to focus their attention onto this important histopathological
      group. Addressing more precisely defined clinico-pathological entities will also
      help to clarify underlying pathomechanisms and, thereby, improve treatment
      strategies for patients with difficult-to-treat epilepsies.

PMID- 21726502
TI  - Leptomeningeal melanocytosis in an adult male without large congenital nevi: a
      rare and atypical case of neurocutaneous melanosis.
AB  - Leptomeningeal melanocytosis is a primary melanocytic lesion of the central
      nervous system that is characterized by diffuse melanocytic infiltration of the
      leptomeninges. It is seen almost exclusively in children with large congenital
      nevi and together the findings form a dermatologic syndrome known as
      neurocutaneous melanosis. We report a rare and atypical case of a 31-year-old
      adult male with no evident congenital melanocytic lesions who presented with
      neurologic symptoms and was found to have leptomeningeal melanocytosis. The brain
      biopsy demonstrated a conspicuous but benign-appearing melanocytic infiltrate
      that was discordant with the severity of the patient's symptoms. Ultimately, the
      patient was suspected to represent a case of former fruste neurocutaneous
      melanosis. Herein the relevant clinical and histopathologic features are
      discussed along with a brief review of the literature.

PMID- 21726503
TI  - Ossification of arachnoid granulations with associated hydrocephalus.
AB  - An autopsy was performed on a 26-year-old female with clinical history of
      hydrocephalus since birth. The dissection of the head and the histopathological
      examination demonstrated ossification of the arachnoid granulations and
      hydrocephalus. Arachnoid ossification usually involves the meninges covering
      spinal cord and rarely occurs within the cranial cavity. Intracranial arachnoid
      ossification is not reported causing any complications. To our knowledge, this is
      the first case of ossification of the arachnoid granulations complicated with
      hydrocephalus.

PMID- 21726504
TI  - Tumefactive demyelination and glioblastoma: a rare collision lesion.
AB  - OBJECTIVE: Inflammatory demyelination occasionally forms a solitary mass lesion
      clinically and radiographically indistinguishable from glioma, replete with
      enhancement and mass effect. Termed "tumefactive demyelination" it often prompts
      a brain biopsy. DESIGN: We undertook neuroimaging and morphologic analysis of a
      unifocal demyelinating lesion intimately associated with glioblastoma. MRI
      characteristics of the lesion were assessed as were biopsy and resection
      specimens by both histological and immunohistochemical methods. RESULTS: The
      patient, a 49-year-old woman, presented with subacute onset headaches. An MRI T1W
      scan revealed a hemispheric mass with centrally reduced signal and ring
      enhancement. T2W images showed increased central signal with a rim of reduced
      signal co-localized to the enhancing ring. A biopsy was initially misinterpreted
      as demyelination alone, given abundance of histiocytes, the presence of
      hypertrophic astrocytes with micronuclei ("Creutzfeldt-Peters cells"), and
      occasional mitoses. Upon consultative review, two histologically distinct
      components, one inflammatory demyelination and the other an anaplastic
      astrocytoma were revealed. Subsequent complete resection of the abnormality
      demonstrated a WHO grade IV astrocytoma (glioblastoma multiforme). CONCLUSION:
      Our experience underscores the importance of adequate tissue sampling during
      biopsy for suspected glioma, and confirms the fact that active inflammatory
      demyelination may coexist with a high-grade glioma. Despite detailed study, the
      basis for the association remains elusive.

PMID- 21726505
TI  - Prolactin-cell adenoma with signet-ring cells: a case report.
AB  - OBJECTIVE: Signet-ring cell changes in the pituitary adenomas are extremely rare.
      To date, there have been only two reports documenting signet-ring cells in
      pituitary adenomas, one in a growth-hormone cell adenoma and the other in a
      nullcell adenoma. This report describes, for the first time, signet-ring cells in
      a prolactincell adenoma. CASE HISTORY: The patient is a 46-year-old male who
      presented with severe headache and acute on chronic visual loss. Radiographic
      studies demonstrated a large cystic pituitary lesion with evidence of pituitary
      apoplexy. Laboratory values were consistent with a prolactin-cell adenoma. The
      patient underwent transsphenoidal resection of the prolactin-cell adenoma with
      significant post-operative improvement. RESULTS: The tumor was composed of sheets
      of monomorphic round cells with conspicuous nuclei and granular cytoplasm,
      consistent with pituitary adenoma. Many cells had eccentric, often crescentic
      shaped nuclei, imparting a signet-ring appearance and immunostaining was positive
      for prolactin, denoting an atypical prolactin-cell adenoma. The MIB-1 labeling
      index was slightly elevated. Electron microscopy demonstrated the presence of
      vacuolated areas in the cytoplasm that were not membrane bound and did not have
      specific inclusions. DISCUSSION: This case augments the literature on pituitary
      adenomas with signet-ring cells. The clinical significance of signet-ring cells
      in pituitary adenomas is unknown. Accumulation of clinical cases, together with
      the advances in molecular techniques and experimental models, may yield further
      insight.

PMID- 21726506
TI  - Dysembryoplastic neuroepithelial tumor and calcifying pseudoneoplasms of the
      neuraxis: a collision of two seizure-associated lesions.
AB  - Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm
      typically associated with intractable, partial complex seizures in children and
      young adults. The authors present a case in which a DNET in a 45-year-old male
      was accompanied by a so-called "calcifying pseudoneoplasm of the neural axis"
      (CPNA), a rare tumefactive lesion considered reactive in nature. An MRI scan of
      the brain revealed a right temporal lobe abnormality with characteristics of DNT
      but no apparent calcification. Histologically, it exhibited classic features of
      DNET and an overlying meningeal- based, partially ossified, chondrocalcific
      lesion morphologically characteristic of CPNA. The association of DNET and CPNA
      has not been previously reported. The literature relevant to these two seizure
      associated lesions is reviewed.

PMID- 21726507
TI  - Brain metastases as first clinical manifestation of ovarian carcinoma.

PMID- 21726508
TI  - A multinodular ganglioglioma with ependymal differentiation.

PMID- 21726509
TI  - Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis
      in the United States.
AB  - BACKGROUND & AIMS: The relative frequency of nonalcoholic steatohepatitis (NASH)
      as an indication for liver transplantation and comparative outcomes following
      transplantation are poorly understood. METHODS: We analyzed the Scientific
      Registry of Transplant Recipients for primary adult liver transplant recipients
      from 2001 to 2009. RESULTS: From 2001 to 2009, 35,781 patients underwent a
      primary liver transplant, including 1959 for who NASH was the primary or
      secondary indication. The percentage of patients undergoing a liver transplant
      for NASH increased from 1.2% in 2001 to 9.7% in 2009. NASH is now the third most
      common indication for liver transplantation in the United States. No other
      indication for liver transplantation increased in frequency during the study
      period. Compared with other indications for liver transplantation, recipients
      with NASH are older (58.5+/-8.0 vs 53.0+/-8.9 years; P<.001), have a larger body
      mass index (>30 kg/m2) (63% vs 32%; P<.001), are more likely to be female (47% vs
      29%; P<.001), and have a lower frequency of hepatocellular carcinoma (12% vs 19%;
      P<.001). Survival at 1 and 3 years after liver transplantation for NASH was 84%
      and 78%, respectively, compared with 87% and 78% for other indications (P=.67).
      Patient and graft survival for liver recipients with NASH were similar to values
      for other indications after adjusting for level of creatinine, sex, age, and body
      mass index. CONCLUSIONS: NASH is the third most common indication for liver
      transplantation in the United States and is on a trajectory to become the most
      common. Outcomes for patients undergoing a liver transplant for NASH are similar
      to those for other indications.

PMID- 21726510
TI  - Chronic intestinal inflammation induces stress-response genes in commensal
      Escherichia coli.
AB  - BACKGROUND & AIMS: Intestinal microbes induce homeostatic mucosal immune
      responses, but can also cause inappropriate immune activation in genetically
      susceptible hosts. Although immune responses to bacterial products have been
      studied extensively, little is known about how intestinal inflammation affects
      functions of commensal luminal microbes. METHODS: Microarrays and real-time
      polymerase chain reaction were used to profile transcriptional changes in luminal
      bacteria from wild-type and IL-10(-/-) mice monoassociated with a nonpathogenic,
      murine isolate of Escherichia coli (NC101, which causes colitis in gnotobiotic IL
      10(-/-) mice). Colonic inflammation and innate and adaptive immune responses were
      measured in wild-type and IL-10(-/-) mice monoassociated with mutant NC101 that
      lack selected, up-regulated genes, and in IL-10(-/-) mice that were colonized
      with a combination of mutant and parental NC101. We measured intracellular
      survival of bacteria within primary macrophages from mice and resulting
      production of tumor necrosis factor. RESULTS: Bacteria from IL-10(-/-) mice with
      colitis had significant up-regulation of the stress-response regulon, including
      the small heat shock proteins IbpA and IbpB that protect E coli from oxidative
      stress, compared to healthy, wild-type controls. In IL-10(-/-) mice, expression
      of ibpAB reduced histologic signs of colon inflammation, secretion of interleukin
      12/23p40 in colonic explant cultures, serologic reactivity to NC101 antigens, and
      secretion of interferon-gamma by stimulated mesenteric lymph node cells.
      Infection of primary macrophages by bacteria that express ibpAB was associated
      with decreased intracellular survival and reduced secretion of tumor necrosis
      factor. CONCLUSIONS: Chronic intestinal inflammation causes functional
      alterations in gene expression in commensal gut bacterium (E coli NC101). Further
      studies of these expression patterns might identify therapeutic targets for
      patients with inflammatory bowel diseases.

PMID- 21726511
TI  - Host response to translocated microbial products predicts outcomes of patients
      with HBV or HCV infection.
AB  - BACKGROUND & AIMS: Chronic infection with hepatitis B or C virus (HBV or HCV) is
      a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation
      of gut microbial products into the systemic circulation might increase because of
      increased intestinal permeability, bacterial overgrowth, or impaired clearance of
      microbial products by Kupffer cells. We investigated whether the extent and
      progression of liver disease in patients with chronic HBV or HCV infection are
      associated with microbial translocation and subsequent activation of monocytes.
      METHODS: In a retrospective study, we analyzed data from 16 patients with minimal
      fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma
      levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and
      interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS)
      by the limulus amebocyte lysate assay, at presentation and after antiviral
      treatment. RESULTS: Compared with uninfected individuals, HCV- and HBV-infected
      individuals had higher plasma levels of LPS, intestinal fatty acid binding
      protein (indicating enterocyte death), sCD14 (produced upon LPS activation of
      monocytes), and interleukin-6. Portal hypertension, indicated by low platelet
      counts, was associated with enterocyte death (P=.045 at presentation, P<.0001
      after therapy). Levels of sCD14 correlated with markers of hepatic inflammation
      (P=.02 for aspartate aminotransferase, P=.002 for ferritin) and fibrosis (P<.0001
      for gamma-glutamyl transpeptidase, P=.01 for alkaline phosphatase, P<.0001 for
      alpha-fetoprotein). Compared to subjects with minimal fibrosis, subjects with
      severe fibrosis at presentation had higher plasma levels of sCD14 (P=.01) and
      more hepatic CD14+ cells (P=.0002); each increased risk for disease progression
      (P=.0009 and P=.005, respectively). CONCLUSIONS: LPS-induced local and systemic
      inflammation is associated with cirrhosis and predicts progression to end-stage
      liver disease in patients with HBV or HCV infection.

PMID- 21726513
TI  - Characterization of Sry-related HMG box group F genes in zebrafish hematopoiesis.
AB  - OBJECTIVE: The roles of Sry-related HMG box (Sox) genes in zebrafish
      hematopoiesis are not clearly defined. In this study, we have characterized the
      sequence homology, gene expression, hematopoietic functions, and regulation of
      sox genes in F group (SoxF) in zebrafish embryos. MATERIALS AND METHODS:
      Expression of zebrafish SoxF genes were analyzed by whole-mount in situ
      hybridization, reverse transcription polymerase chain reaction, and real-time
      reverse transcription polymerase chain reaction of erythroid cells obtained from
      Tg(gata1:GFP) embryos by fluorescence-activated cell sorting. Roles of SoxF genes
      were analyzed in zebrafish embryos using morpholino knockdown and analyzed by
      whole-mount in situ hybridization and real-time reverse transcription polymerase
      chain reaction. Embryo patterning and vascular development were analyzed.
      RESULTS: All members, except sox17, contained a putative beta-catenin binding
      site. sox7 and 18 expressed primarily in the vasculature. sox17 expressed in the
      intermediate cell mass and its knockdown significantly reduced primitive
      erythropoiesis at 18 hours post-fertilization (hpf). Definitive hematopoiesis was
      unaffected. Concomitant sox7 and sox18 knockdown disrupted vasculogenesis and
      angiogenesis, but not hematopoiesis. sox32 knockdown delayed medial migration of
      hematopoietic and endothelial progenitors at 18 hpf and abolished cmyb expression
      at the caudal hematopoietic tissue at 48 hpf. These defects could be prevented by
      delaying its knockdown using a caged sox32 morpholino uncaged at 10 hpf.
      Knockdown of SoxF genes significantly upregulated their own expression and that
      of sox32 also upregulated sox18 expression. CONCLUSIONS: sox17 helped to maintain
      primitive hematopoiesis, whereas sox7 and sox18 regulated angiogenesis and
      vasculogenesis. sox32 affected both vascular and hematopoietic development
      through its effects on medial migration of the hematopoietic and endothelial
      progenitors.

PMID- 21726512
TI  - Hepatic overexpression of abcb11 promotes hypercholesterolemia and obesity in
      mice.
AB  - BACKGROUND & AIMS: ABCB11 is a canalicular transport protein that controls the
      rate-limiting step in hepatic bile acid secretion. Its expression levels vary in
      humans, and it is not clear how these variations affect lipid metabolism. We
      investigated whether overexpression of Abcb11 in mice increases lipid absorption
      in the intestine and affects the development of obesity or hypercholesterolemia.
      METHODS: Transgenic mice that overexpress Abcb11 in liver (TTR-Abcb11) and FVB/NJ
      mice (controls) were fed a high-cholesterol or high-fat diet for 12 weeks.
      Intestinal lipid absorption was measured by the dual fecal isotope method. Energy
      expenditure was measured by indirect calorimetry. The bile acid pool was analyzed
      by high-performance liquid chromatography. RESULTS: TTR-Abcb11 mice had a nearly
      2-fold increase in intestinal cholesterol absorption compared with controls. TTR
      Abcb11 mice fed a high-cholesterol diet had greater increases in plasma and
      hepatic levels of cholesterol and became more obese than controls; they also had
      increased intestinal absorption of fatty acids and decreased energy expenditure.
      In the TTR-Abcb11 mice, the sizes of plasma and total bile acid pools were
      reduced; the bile acid pool contained more species of hydrophobic bile acids
      compared with controls. CONCLUSIONS: Hepatic overexpression of Abcb11 in mice
      promotes diet-induced obesity and hypercholesterolemia; increased intestinal
      cholesterol absorption by hydrophobic bile acids might cause these features.
      Increased absorption of fatty acids in the intestine and reduced expenditure of
      energy could increase weight gain in TTR-Abcb11 mice. In humans, variations in
      expression of ABCB11 might confer genetic susceptibility to diet-induced
      hyperlipidemia and obesity.

PMID- 21726514
TI  - Kinase suppressor of Ras (KSR1) modulates multiple kit-ligand-dependent mast cell
      functions.
AB  - The intricately regulated Ras pathway coordinates multiple kit-ligand-induced
      mast cell functions, including chemotaxis, proliferation, and degranulation.
      However, the intracellular proteins that modulate the intensity and duration of
      stem cell factor-induced signals and the consequent cellular response are
      incompletely understood. Scaffolding proteins coordinate the spatial organization
      of mitogen-activated protein kinase proteins that may potentiate and/or inhibit
      cell functions. The kinase suppressor of Ras (KSR1) protein is known to function
      as a molecular scaffold and coordinates the organization of Raf/Mek/Erk in
      response to receptor tyrosine kinases. However, the impact of KSR1 in myeloid
      mast cell functions and in response to stem cell factor remains unknown. In the
      present study, we investigated the role of KSR1 in regulating cellular functions
      of bone marrow-derived mast cells of KSR1-deficient ((-/-)) mice. Genetic
      disruption of KSR1 resulted in both striking reductions in kit-ligand-mediated
      proliferation and degranulation, which are commonly attributed to mitogen
      activated protein kinase signals. Surprisingly, disruption of the KSR1 scaffold
      also resulted in a decline in migration that is generally not linked to Raf-Erk
      signals. We found that loss of KSR1 does impact the biochemical activation of p21
      activated kinase, a kinase that is known to modulate Raf-Erk signals and also F
      actin polymerization key to mast cell migration. Collectively, these studies
      demonstrate that the scaffolding protein KSR1 has an important role in multiple
      kit-ligand-mediated mast cell functions. This study elucidates varied mast cell
      physiological functions for KSR1, including those related to cytoskeletal
      organization, and it suggests a novel molecular target for attenuating mast cell
      mediated inflammation.

PMID- 21726515
TI  - Differential outcomes in prediabetic vs. overtly diabetic NOD mice
      nonmyeloablatively conditioned with costimulatory blockade.
AB  - OBJECTIVE: Autoimmune diabetes can be reversed with mixed chimerism. However, the
      myelotoxic agents currently required to establish chimerism have prevented the
      translation of this approach to the clinic. Here, we investigated whether
      multimodal costimulatory blockade would enhance chimerism and promote islet
      allograft tolerance in spontaneously diabetic nonobese diabetic (NOD) mice.
      MATERIALS AND METHODS: Prediabetic and spontaneously diabetic NOD mice were
      preconditioned with anti-CD8 monoclonal antibody before conditioning with 500 cGy
      total body irradiation and transplantation with 30 * 10(6) B10.BR bone marrow
      cells. Overtly diabetic animals were conditioned similarly and transplanted with
      300 to 400 B10.BR islets. After irradiation, both groups of recipients were
      treated with anti-CD154, anti-OX40L, and anti-inducible T-cell costimulatory
      monoclonal antibodies. Urine, blood glucose levels, and chimerism were monitored.
      RESULTS: Conditioning of NOD mice with costimulatory blockade significantly
      enhanced engraftment, with 61% of mice engrafting at 1 month. Eleven of 12
      chimeric animals with engraftment at 1 month remained diabetes-free over a 12
      month follow-up, whereas nonchimeric animals progressed to diabetes. In contrast,
      similar conditioning prolonged islet allograft survival in only 2 of 11 overtly
      diabetic NOD recipients. Chimerism levels in the 9 islet rejector animals were
      0%. CONCLUSIONS: Although nonmyeloablative conditioning reversed the autoimmune
      process in prediabetic NOD mice, the same regimen was significantly less
      effective in establishing chimerism and reversing autoimmune diabetes in
      spontaneously diabetic NOD mice.

PMID- 21726517
TI  - Re: Yann Neuzillet, Xavier Tillou, Romain Mathieu, et al. Renal cell carcinoma
      (RCC) in patients with end-stage renal disease exhibits many favourable clinical,
      pathologic, and outcome features compared with RCC in the general population. Eur
      urol 2011; 60: 366-73.

PMID- 21726518
TI  - Re:Altaf Mangera, Jacob M. Patterson, Christopher R. Chapple. A systematic review
      of graft augmentation urethroplasty techniques for the treatment of anterior
      urethral strictures. Eur urol 2011; 59: 797-814.

PMID- 21726519
TI  - Postablation asymptomatic cerebral lesions: long-term follow-up using magnetic
      resonance imaging.
AB  - BACKGROUND: Catheter ablation of atrial fibrillation (AF) is complicated by
      cerebral emboli resulting in acute ischemia. Recently, cerebral ischemic
      microlesions have been identified with diffusion-weighted magnet resonance
      imaging (MRI). OBJECTIVE: The clinical course and longer-term characteristics of
      these lesions are not known and were investigated in this study. METHODS: Of 86
      patients, 33 (38%) had new asymptomatic cerebral lesions documented on MRI after
      catheter ablation for AF; 14 of these 33 (42%) underwent repeat MRI at different
      time intervals (2 weeks to 1 year) during follow-up, and clinical symptoms as
      well as size and number of residual lesions were documented. RESULTS: In
      postablation cerebral MRI, 50 new lesions were identified (3.6 lesions/patient)
      in 14 patients. No patient presented any neurological symptoms. Distribution of
      the lesions was predominantly in the left hemisphere (60%) and the cerebellum
      (26%); 52% of the lesions were small (<=3 mm maximum diameter), 42% were medium
      (4 to 10 mm) and 3 lesions (6%) had a maximum diameter >10 mm. Follow-up MRI
      after a median of 3 months revealed 3 residual lesions in 3 of 14 patients
      corresponding to the large acute postablation lesions (>10 mm). The remaining 47
      of 50 (94%) of the small or medium-sized lesions were not detectable at follow-up
      evaluation. CONCLUSIONS: Most asymptomatic cerebral lesions observed acutely
      after AF ablation procedures were <=10 mm in diameter. 94% of all lesions healed
      without scarring at follow-up >2 weeks after ablation. The larger acute lesions
      produced chronic glial scars. Neither chronic nor acute lesions were associated
      with neurological symptoms.

PMID- 21726520
TI  - Mapping of Wuchereria bancrofti infection in children and adolescents in an
      endemic area of Brazil.
AB  - A parasitological survey was conducted among children and adolescents in the
      municipality of Jaboatao dos Guararapes, Brazil to describe the occurrence and
      spatial distribution of lymphatic filariasis. Microfilaraemia was investigated
      through the thick smear technique, using 50 MUl of capillary blood that was
      collected at night. The spatial analysis used a digital base map of the
      municipality, divided into districts, which were classified as hypoendemic,
      mesoendemic or hyperendemic. 8670 children were examined and 96 cases of
      microfilaraemia were identified (1.1%). The prevalence rate did not differ
      significantly between the sexes. Occurrences of filarial infection increased with
      increasing age: the greatest prevalence was recorded between 15 and 18 years of
      age (P<0.05). There were 49 reports of clinical manifestations. The spatial
      distribution of microfilaraemia according to residential district showed that 13
      (54.2%) of the 24 districts investigated were positive. Approximately 33% of the
      districts were hyperendemic. The results demonstrated that the pediatric
      population had intense early exposure to the parasite, thus characterizing
      filariasis as endemic in the municipality. The spatial analysis allowed
      identification of areas with greater occurrence of infection among children, and
      showed localities where the populations most exposed to transmission were
      concentrated. Epidemiological surveillance of microfilaraemia among children and
      spatial analysis are important local transmission indicators and form instruments
      for planning actions within the Global Program to Eliminate Lymphatic Filariasis,
      since they make it possible to identify priority areas.

PMID- 21726521
TI  - Affinity characterization-mass spectrometry methodology for quantitative analyses
      of small molecule protein binding in solution.
AB  - Affinity characterization by mass spectrometry (AC-MS) is a novel LC-MS
      methodology for quantitative determination of small molecule ligand binding to
      macromolecules. Its most distinguishing feature is the direct determination of
      all three concentration terms of the equilibrium binding equation, i.e., (M),
      (L), and (ML), which denote the macromolecule, ligand, and the corresponding
      complex, respectively. Although it is possible to obtain the dissociation
      constant from a single mixing experiment, saturation analyses are still valuable
      for assessing the overall binding phenomenon based on an established formalism.
      In addition to providing the prerequisite dissociation constant and binding
      stoichiometry, the technique also provides valuable information about the actual
      solubility of both macromolecule and ligand upon dilution and mixing in binding
      buffers. The dissociation constants and binding mode for interactions of DNA
      primase and thymidylate synthetase (TS) with high and low affinity small molecule
      ligands were obtained using the AC-MS method. The data were consistent with the
      expected affinity of TS for these ligands based on dissociation constants
      determined by alternative thermal-denaturation techniques: TdF or TdCD, and also
      consistent enzyme inhibition constants reported in the literature. The validity
      of AC-MS was likewise extended to a larger set of soluble protein-ligand systems.
      It was established as a valuable resource for counter screen and structure
      activity relationship studies in drug discovery, especially when other classical
      techniques could only provide ambiguous results.

PMID- 21726522
TI  - Fluorescence-based evaluation of shRNA efficacy.
AB  - RNA interference is a cellular mechanism regulating levels of mRNAs. It has been
      widely exploited to knock down specific protein targets. The selected interfering
      RNA sequence greatly influences its ability to knock down the target. Here we
      present a method for constructing multiple testing plasmids which express small
      hairpin RNAs (shRNA) targeting different regions of an mRNA. A simple
      fluorescence test in cultured cells allows convenient evaluation of mRNA
      knockdown by many different shRNAs on 96-well plates. We show that software
      predicted shRNAs have varying efficacies and only 2 of the 7 tested shRNAs
      significantly knocked down their targets.

PMID- 21726523
TI  - Amplification of agonist stimulation of human G-protein-coupled receptor
      signaling in yeast.
AB  - G-protein-coupled receptors (GPCRs) are considered as important targets for drug
      discovery. The yeast Saccharomyces cerevisiae is an attractive host for high
      throughput screening of agonistic ligands for human GPCRs because it can simplify
      the complicated signaling pathways that are present in mammalian cell lines.
      Unfortunately, many human GPCRs induce only partial signal activation in yeast
      cells depending on their coupling efficiency with yeast G-proteins. This problem
      often results in unsatisfactory detection sensitivity, thereby resulting in a
      limitation to yeast-based detection systems. Here we introduce a new highly
      sensitive detection method that provides robust agonist detection of human GPCRs.
      Our strategy is designed to invoke feedback activation of signals within yeast G
      protein signaling pathways. Briefly, agonist stimulation of human GPCRs triggers
      expression of an artificial signal activator that amplifies signaling. We chose
      human somatostatin receptor subtype 5 (hSSTR5) as a model of a human GPCR.
      Investigation of the response of hSSTR5-expressing yeast to various
      concentrations of somatostatin demonstrated that feedback activation of the
      signal can successfully improve the detection limit and the maximum level of
      signaling. This novel approach will enhance the usefulness of yeast-based
      screening of agonistic ligands for a variety of human GPCRs.

PMID- 21726524
TI  - Development of a novel DnaE intein-based assay for quantitative analysis of G
      protein-coupled receptor internalization.
AB  - G-protein-coupled receptor (GPCR) internalization provides a G-protein-subtype
      independent method for assaying agonist-stimulated activation of receptors. We
      have developed a novel assay that allows quantitative analysis of GPCR
      internalization based on the interaction between activated GPCRs and beta
      arrestin2 and on Nostoc punctiforme DnaE intein-mediated reconstitution of
      Renilla luciferase fragments. This assay system was validated using four
      functionally divergent GPCRs treated with agonists and antagonists. The EC(50)
      values obtained for the known agonists and antagonists are in close agreement
      with the results of previous reports, indicating that this assay system is
      sensitive enough to permit quantification of GPCR internalization. This rapid and
      quantitative assay, therefore, could be used universally as a functional cell
      based assay for GPCR high-throughput screening during drug discovery.

PMID- 21726525
TI  - Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in
      vascular smooth muscle cells.
AB  - Naphthoquinone derivatives have been reported to possess various pharmacological
      activities, such as antiplatelet, anticancer, antifungal, and antiviral
      properties. In this study, we investigated the effects of a newly-synthesized
      naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2
      decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the
      underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited
      PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2
      decylamino-DMNQ did not affect PDGF-Rbeta or Akt, it did inhibit the
      phosphorylation of Erk1/2 and PLCgamma1 induced by PDGF. Moreover, 2-decylamino
      DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the
      G(0)/G(1) phase, including the suppression of pRb phosphorylation and a decrease
      in PCNA expression, which was related to the downregulation of cell cycle
      regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that
      both U0126, an Erk1/2 inhibitor, and U73122, a PLCgamma inhibitor, increased the
      proportion of cells in the G(0)/G(1) phase of the cell cycle. Thus, these results
      suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC
      proliferation and the mechanism of this action is through cell cycle arrest at
      the G(0)/G(1) phase. This may be a useful tool for studying interventions for
      vascular restenosis in coronary revascularization procedures and stent
      implantation.

PMID- 21726526
TI  - Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage
      dependent sodium channel.
AB  - Mutations in the neuronal Nav1.1 voltage-gated sodium channel are responsible for
      mild to severe epileptic syndromes. The ubiquitous calcium sensor calmodulin
      (CaM) bound to rat brain Nav1.1 and to the human Nav1.1 channel expressed by a
      stably transfected HEK-293 cell line. The C-terminal region of the channel, as a
      fusion protein or in the yeast two-hybrid system, interacted with CaM via a
      consensus C-terminal motif, the IQ domain. Patch clamp experiments on HEK1.1
      cells showed that CaM overexpression increased peak current in a calcium
      dependent way. CaM had no effect on the voltage-dependence of fast inactivation,
      and accelerated the inactivation kinetics. Elevating Ca(++) depolarized the
      voltage-dependence of fast inactivation and slowed down the fast inactivation
      kinetics, and for high concentrations this effect competed with the acceleration
      induced by CaM alone. Similarly, the depolarizing action of calcium antagonized
      the hyperpolarizing shift of the voltage-dependence of activation due to CaM
      overexpression. Fluorescence spectroscopy measurements suggested that Ca(++)
      could bind the Nav1.1 C-terminal region with micromolar affinity.

PMID- 21726527
TI  - FBN1 isoform expression varies in a tissue and development-specific fashion.
AB  - Mutations in FBN1 cause Marfan syndrome, a heritable disorder of connective
      tissue. FBN1 encodes the extracellular matrix protein, fibrillin. Our objective
      was to elucidate the extent that variation in RNA splicing contributes to FBN1
      isoforms. To identify FBN1 splice variants, we scanned each of its 64 internal
      exons in a set of pooled human brain cDNA samples. FBN1 splicing is generally
      efficient as we identified only two variants. Neither variant has previously been
      reported in the literature and include (i) an isoform which contains a cryptic
      105 basepair exon between exons 54 and 55 (54A-FBN1) and (ii) an isoform which
      contains a cryptic 62 basepair exon between exons 57 and 58 (57A-FBN1). We
      compared 57A-FBN1 and FBN1 expression in multiple human tissues, including adult
      skeletal muscle and brain, as well as fetal skeletal muscle, brain, liver, aorta,
      lung, skin, and heart. 57A-FBN1 represents 8-44% of FBN1 mRNA and varies in a
      tissue- and development-specific fashion. In adult brain, 57A-FBN1 represented
      39+/-3 (%, mean+/-SD) of total FBN1 expression. In contrast, 57A-FBN1 represented
      19+/-2 (%, mean+/-SD) of FBN1 expression in skeletal muscle. In fetal tissue, the
      57A-FBN1 proportion was highest in brain (27%) and low elsewhere, e.g., skin,
      aorta and lung (9-13%). In summary, a significant proportion of FBN1 is expressed
      as 57A-FBN1 and this proportion varies in a tissue- and development-specific
      fashion. Since the 57A insertion creates a premature stop codon that mimics
      Marfan-associated mutations, the protein encoded by 57A-FBN1 is likely to not be
      functional. These results suggest that altered splicing may modulate disease
      severity, regulate FBN1 expression, and potentially represent a therapeutic
      target.

PMID- 21726528
TI  - Colonization of collagen scaffolds by adipocytes derived from mesenchymal stem
      cells of the common marmoset monkey.
AB  - In regenerative medicine, human cell replacement therapy offers great potential,
      especially by cell types differentiated from immunologically and ethically
      unproblematic mesenchymal stem cells (MSCs). In terms of an appropriate carrier
      material, collagen scaffolds with homogeneous pore size of 65MUm were optimal for
      cell seeding and cultivating. However, before clinical application and
      transplantation of MSC-derived cells in scaffolds, the safety and efficiency, but
      also possible interference in differentiation due to the material must be
      preclinically tested. The common marmoset monkey (Callithrix jacchus) is a
      preferable non-human primate animal model for this aim due to its genetic and
      physiological similarities to the human. Marmoset bone marrow-derived MSCs were
      successfully isolated, cultured and differentiated in suspension into adipogenic,
      osteogenic and chondrogenic lineages by defined factors. The differentiation
      capability could be determined by FACS. Specific marker genes for all three cell
      types could be detected by RT-PCR. Furthermore, MSCs seeded on collagen I
      scaffolds differentiated in adipogenic lineage showed after 28days of
      differentiation high cell viability and homogenous distribution on the material
      which was validated by calcein AM and EthD staining. As proof of adipogenic
      cells, the intracellular lipid vesicles in the cells were stained with Oil Red O.
      The generation of fat vacuoles was visibly extensive distinguishable and
      furthermore determined on the molecular level by expression of specific marker
      genes. The results of the study proved both the differential potential of
      marmoset MSCs in adipogenic, osteogenic and chondrogenic lineages and the
      suitability of collagen scaffolds as carrier material undisturbing
      differentiation of primate mesenchymal stem cells.

PMID- 21726529
TI  - Regulation of gap junction function and Connexin 43 expression by cytochrome P450
      oxidoreductase (CYPOR).
AB  - Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring
      enzyme containing both FAD and FMN as co-factors, which provides the reducing
      equivalents to various redox partners, such as cytochromes P450 (CYPs), heme
      oxygenase (HO), cytochrome b(5) and squalene monooxygenase. Human patients with
      severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial
      synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS).
      To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple
      osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR
      decreased the expression of Connexin 43 (Cx43), known to play a critical role in
      bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap
      Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter
      luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock
      down cells was due to transcriptional repression. Primary osteoblasts isolated
      from bone specific Por knock-down mice calvariae confirmed the findings in the
      cell lines. Taken together, our study provides novel insights into the regulation
      of gap junction function by CYPOR and suggests that Cx43 may play an important
      role(s) in CYPOR-mediated bone defects seen in patients.

PMID- 21726530
TI  - A partially folded structure of amyloid-beta(1-40) in an aqueous environment.
AB  - Aggregation of the Abeta(1-40) peptide is linked to the development of
      extracellular plaques characteristic of Alzheimer's disease. While previous
      studies commonly show the Abeta(1-40) is largely unstructured in solution, we
      show that Abeta(1-40) can adopt a compact, partially folded structure. In this
      structure (PDB ID: 2LFM), the central hydrophobic region of the peptide forms a
      3(10) helix from H13 to D23 and the N- and C-termini collapse against the helix
      due to the clustering of hydrophobic residues. Helical intermediates have been
      predicted to be crucial on-pathway intermediates in amyloid fibrillogenesis, and
      the structure presented here presents a new target for investigation of early
      events in Abeta(1-40) fibrillogenesis.

PMID- 21726531
TI  - Single particle analysis of tau oligomer formation induced by metal ions and
      organic solvents.
AB  - Pathological aggregates of tau protein are found in several neurodegenerative
      diseases termed 'tauopathies'. Increasing evidence indicates that tau oligomer
      species rather than the large amyloid cytoplasmic inclusions relevant for
      histopathological diagnosis might be crucial for cellular damage and
      neurodegeneration. Trivalent metal ions and polyanionic structures like heparin
      or arachidonic acid have been shown to induce tau aggregation. However, little is
      known about early processes of tau aggregation. In this study, we applied
      fluorescence correlation spectroscopy (FCS) and scanning for intensely
      fluorescent targets (SIFT) to investigate oligomer formation of tau protein at
      nanomolar protein concentrations at the single-particle level. Our results
      indicate that the formation of distinct tau oligomers is induced by the trivalent
      metal ions Fe(3+) and Al(3+) and by organic solvents like DMSO, respectively. In
      contrast, bivalent metal ions (Cu(2+), Zn(2+), Mn(2+), Ca(2+), Mg(2+)) had no
      effect. While DMSO-induced small tau oligomers are relatively stable in solution,
      dynamic remodeling can be initiated by non-ionic detergents. Moreover Al(3+)
      induces rapid formation of a different oligomer species of larger size. Our
      results provide further insights into early tau oligomerization and aggregation
      dynamics.

PMID- 21726532
TI  - A novel protein kinase C target site in protein kinase D is phosphorylated in
      response to signals for cardiac hypertrophy.
AB  - Protein kinase D (PKD) regulates cardiac myocyte growth and contractility through
      phosphorylation of proteins such as class IIa histone deacetylases (HDACs) and
      troponin I (TnI). In response to agonists that activate G-protein-coupled
      receptors (GPCRs), PKD is phosphorylated by protein kinase C (PKC) on two serine
      residues (Ser-738 and Ser-742 in human PKD1) within an activation loop of the
      catalytic domain, resulting in stimulation of PKD activity. Here, we identify a
      novel PKC target site located adjacent to the auto-inhibitory pleckstrin homology
      (PH) domain in PKD. This site (Ser-412 in human PKD1) is conserved in each of the
      three PKD family members and is efficiently phosphorylated by multiple PKC
      isozymes in vitro. Employing a novel anti-phospho-Ser-412-specific antibody, we
      demonstrate that this site in PKD is rapidly phosphorylated in primary cardiac
      myocytes exposed to hypertrophic agonists, including norepinephrine (NE) and
      endothelin-1 (ET-1). Differential sensitivity of this event to pharmacological
      inhibitors of PKC, and data from in vitro enzymatic assays, suggest a predominant
      role for PKCdelta in the control of PKD Ser-412 phosphorylation. Together, these
      data suggest a novel, signal-dependent mechanism for controlling PKD function in
      cardiac myocytes.

PMID- 21726533
TI  - Sustained expression of lipocalin-type prostaglandin D synthase in the antisense
      direction positively regulates adipogenesis in cloned cultured preadipocytes.
AB  - Adipocytes express preferentially lipocalin-type prostaglandin (PG)D synthase (L
      PGDS) that is responsible for the biosynthesis of PGD(2) and other related
      prostanoids with pro-adipogenic or anti-adipogenic effects. To evaluate the role
      of L-PGDS in cultured adipocytes and the precursor cells, we attempted to
      interfere the intracellular expression of L-PGDS in cultured 3T3-L1 preadipocytes
      by stable transfection with a mammalian expression vector having the full-length
      cDNA of L-PGDS oriented in the antisense direction. The cloned transfectants with
      antisense L-PGDS exhibited the reduction in the transcript and protein levels of
      L-PGDS, resulting in the significant inhibition of the PGD(2) synthesis from
      exogenous and endogenous arachidonic acid. By contrast, the synthesis of PGE(2)
      was not influenced appreciably, indicating no interfering effects on
      cyclooxygenases and PGE synthases. The stable transfection with antisense L-PGDS
      induced markedly the stimulation of fat storage in cultured adipocytes during the
      maturation phase. In addition, the spontaneous accumulation of fats occurred in
      the transfectants with antisense L-PGDS without undergoing the stimulation with
      inducing factors. The gene expression studies revealed the enhanced expression of
      adipocyte-specific markers in the transfectants with antisense L-PGDS, indicating
      the up-regulation of adipogenesis program. The stimulated adipogenesis was
      significantly reversed by anti-adipogenic prostanoids including PGE(2) and
      PGF(2alpha), while the storage of fats was additionally enhanced by pro
      adipogenic 15-deoxy- Delta(12,14)-prostaglandin J(2). These results suggest that
      the stably reduced expression levels of L-PGDS regulates positively adipogenesis
      program in a cellular mechanism independent of pro-adipogenic action of PGJ(2)
      series.

PMID- 21726534
TI  - Liberation of desmosine and isodesmosine as amino acids from insoluble elastin by
      elastolytic proteases.
AB  - The development of atherosclerotic lesions and abdominal aortic aneurysms
      involves degradation and loss of extracellular matrix components, such as
      collagen and elastin. Releases of the elastin cross-links desmosine (DES) and
      isodesmosine (IDE) may reflect elastin degradation in cardiovascular diseases.
      This study investigated the production of soluble elastin cross-linking
      structures by proteinases implicated in arterial diseases. Recombinant MMP-12 and
      neutrophil elastase liberated DES and IDE as amino acids from insoluble elastin.
      DES and IDE were also released from insoluble elastin exposed to
      monocyte/macrophage cell lines or human primary macrophages derived from
      peripheral blood monocytes. Elastin oxidized by reactive oxygen species (ROS)
      liberated more unconjugated DES and IDE than did non-oxidized elastin when
      incubated with MMP-12 or neutrophil elastase. These results support the
      exploration of free DES and IDE as biomarkers of elastin degradation.

PMID- 21726535
TI  - Ibuprofen and warfarin modulate allosterically ferrous human serum heme-albumin
      nitrosylation.
AB  - Ferrous human serum heme-albumin (HSA-heme-Fe(II)) displays globin-like
      properties. Here, the effect of ibuprofen and warfarin on kinetics of HSA-heme
      Fe(II) nitrosylation is reported. Values of the second-order rate constant for
      HSA-heme-Fe(II) nitrosylation (k(on)) decrease from 6.3 * 10(6)M(-1)s(-1) in the
      absence of drugs, to 4.1 * 10(5)M(-1)s(-1) and 4.8 * 10(5)M(-1)s(-1), in the
      presence of saturating amounts of ibuprofen and warfarin, respectively, at pH 7.0
      and 20.0 degrees C. From the dependence of k(on) on the drug concentration,
      values of the dissociation equilibrium constant for ibuprofen and warfarin
      binding to HSA-heme-Fe(II) (i.e., K=3.2 * 10(-3)M and 2.6 * 10(-4)M,
      respectively) were determined. The observed allosteric effects could indeed
      reflect ibuprofen and warfarin binding to the regulatory fatty acid binding site
      FA2, which brings about an alteration of heme coordination, slowing down HSA-heme
      Fe(II) nitrosylation. Present data highlight the allosteric modulation of HSA
      heme-Fe(II) reactivity by heterotropic effectors.

PMID- 21726536
TI  - The Saccharomyces cerevisiae ubiquitin E3 ligase Asr1p targets calmodulin for
      ubiquitylation.
AB  - Yeast calmodulin known to be ubiquitylated in vivo in a Ca(2+) dependent manner
      has long remained an orphan substrate. Here we identify Saccharomyces cerevisiae
      Asr1p as an ubiquitin E3 ligase for yeast calmodulin, a protein involved in
      calcium signaling. A short region within Asr1p-C harboring two putative
      calmodulin-binding motifs is sufficient and necessary for interaction with
      calmodulin. The interaction is direct, occurs in vivo and depends on
      physiological concentrations of Ca(2+). A minimal set of purified proteins
      including Asr1p E3 ligase was sufficient for in vitro ubiquitylation of
      calmodulin, a reaction that required a functional Asr1p Ring domain. We propose a
      role of the Asr1p E3 ligase activity in coping with stress.

PMID- 21726537
TI  - Creating a flexible multiple microRNA expression vector by linking precursor
      microRNAs.
AB  - MicroRNAs (miRNAs) are ~22nt non-coding RNA molecules that usually function as
      endogenous repressors of target genes. Many biological processes depend on
      faithful miRNA expression and miRNA profiling has revealed dysregulation of many
      miRNAs in neurological, and cardiovascular diseases, and in cancer. Despite this
      finding, most studies have focused on the function of single miRNAs or miRNA
      clusters. To better address physiologically relevant collaborative miRNA
      interactions, we developed a simple and flexible platform which expresses several
      miRNAs that have different genomic locations from a single transcript using
      endogenous pre-miRNA sequences. As a proof of principle we cloned the miR-34
      tumor suppressor family and showed that the miR-34a/34b/34c vector expresses each
      miRNA at similar levels to individual miRNA containing vectors. Moreover, the miR
      34a/34b/34c vector suppressed cell growth more than the individual miRNA vectors.
      We expect that this platform will be invaluable as a tool to study the complex
      and synergistic interactions of aberrantly expressed miRNAs in human diseases and
      may have applications for use in gene therapy.

PMID- 21726538
TI  - Up-regulation of K(ir)2.1 by ER stress facilitates cell death of brain capillary
      endothelial cells.
AB  - Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to
      maintain brain homeostasis. Cell turnover of BCECs by the balance of cell
      proliferation and cell death is critical for maintaining the integrity of BBB.
      Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress
      inducer, up-regulated inward rectifier K(+) channel (K(ir)2.1) and facilitated
      cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of
      K(ir) channels contributed to the establishment of deeply negative resting
      membrane potential in t-BBEC117. The deep resting membrane potential increased
      the resting intracellular Ca(2+) concentration due to Ca(2+) influx through non
      selective cation channels and thereby partly but significantly regulated cell
      death in t-BBEC117. The present results suggest that the up-regulation of
      K(ir)2.1 is, at least in part, responsible for cell death/cell turnover of BCECs
      induced by a variety of cellular stresses, particularly ER stress, under
      pathological conditions.

PMID- 21726539
TI  - Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on
      proliferation in brain tumor cell models.
AB  - We have investigated in vitro effects of anticancer therapy with the histone
      deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor
      tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of
      glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with
      individual effects of these drugs, combined treatment with gefitinib/4-PB or
      vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival
      in both cell lines. Our results suggest that combined treatment using HDACi and
      RTKi may beneficially affect the outcome of cancer therapy.

PMID- 21726540
TI  - Metabolic depletion of sphingolipids enhances the mobility of the human
      serotonin1A receptor.
AB  - Sphingolipids are essential components of eukaryotic cell membranes. We recently
      showed that the function of the serotonin(1A) receptor is impaired upon metabolic
      depletion of sphingolipids using fumonisin B(1) (FB(1)), a specific inhibitor of
      ceramide synthase. Serotonin(1A) receptors belong to the family of G-protein
      coupled receptors and are implicated in the generation and modulation of various
      cognitive, behavioral and developmental functions. Since function and dynamics of
      membrane receptors are often coupled, we monitored the lateral dynamics of the
      serotonin(1A) receptor utilizing fluorescence recovery after photobleaching
      (FRAP) under these conditions. Our results show an increase in mobile fraction of
      the receptor upon sphingolipid depletion, while the diffusion coefficient of the
      receptor did not exhibit any significant change. These novel results constitute
      the first report on the effect of sphingolipid depletion on the mobility of the
      serotonin(1A) receptor. Our results assume greater relevance in the broader
      context of the emerging role of receptor mobility in understanding cellular
      signaling.

PMID- 21726541
TI  - Drug metabolism by CYP2C8.3 is determined by substrate dependent interactions
      with cytochrome P450 reductase and cytochrome b5.
AB  - Genetic polymorphisms in CYP2C8 can influence the metabolism of important
      therapeutic agents and cause interindividual variation in drug response and
      toxicity. The significance of the variant CYP2C8*3 has been controversial with
      reports of higher in vivo but lower in vitro activity compared to CYP2C8*1. In
      this study, the contribution of the redox partners cytochrome P450 reductase
      (CPR) and cytochrome b5 to the substrate dependent activity of CYP2C8.3 (R139K,
      K399R) was investigated in human liver microsomes (HLMs) and Escherichia coli
      expressed recombinant CYP2C8 proteins using amodiaquine, paclitaxel,
      rosiglitazone and cerivastatin as probe substrates. For recombinant CYP2C8.3,
      clearance values were two- to five-fold higher compared to CYP2C8.1. CYP2C8.3's
      higher k(cat) seems to be dominated by a higher, but substrate specific affinity,
      towards cytochrome b5 and CPR (K(D) and K(m,red)) which resulted in increased
      reaction coupling. A stronger binding affinity of ligands to CYP2C8.3, based on a
      two site binding model, in conjunction with a five fold increase in amplitude of
      heme spin change during binding of ligands and redox partners could potentially
      contribute to a higher k(cat). In HLMs, carriers of the CYP2C8*1/*3 genotype were
      as active as CYP2C8*1/*1 towards the CYP2C8 specific reaction amodiaquine N
      deethylation. Large excess of cytochrome b5 compared to CYP2C8 in recombinant
      systems and HLMs inhibited metabolic clearance, diminishing the difference in
      k(cat) between the two enzymes, and may provide an explanation for the
      discrepancy to in vivo data. In silico studies illustrate the genetic differences
      between wild type and variant on the molecular level.

PMID- 21726542
TI  - Role of DNA damage in atherosclerosis--bystander or participant?
AB  - Atherosclerosis leading to cardiovascular disease is the leading cause of death
      among western populations. Atherosclerosis in characterised by the development of
      a fibrofatty lesion that consists of a diverse cell population, including
      inflammatory cells that create an intensely oxidising environment within the
      vessel. Coupled with normal replication, the local intracellular and
      extracellular environment causes damage to cellular DNA that is recognised and
      repaired by the DNA damage response (DDR) pathway. The role of DNA damage and the
      resulting deregulation of 'normal' cellular behaviour and subsequent loss of cell
      cycle control checkpoints have been widely studied in cancer. However, despite
      the extensive evidence for DNA damage in atherosclerosis, it is only over the
      past two decades that a causative link between DNA damage and atherosclerosis has
      been hypothesised. Whilst atherosclerosis is a feature of human disease
      characterised by defects in DNA damage, currently the role of DNA damage in the
      initiation and progression of atherosclerosis remains highly debated, as a
      'chicken and egg' situation. This review will analyse the evidence for, the
      causes of, and consequences of DNA damage in atherosclerosis, detail the DNA
      damage response pathway that results in these consequences, and highlight
      therapeutic opportunities in this area. We also outline the evidence that DNA
      damage is a cause of both initiation and progression of atherosclerosis, and not
      just a consequence of disease.

PMID- 21726543
TI  - Dimethoxycurcumin, a metabolically stable analogue of curcumin, exhibits anti
      inflammatory activities in murine and human lymphocytes.
AB  - The aim of this study was to investigate whether dimethoxycurcumin (DiMC), a
      synthetic curcumin analogue having higher metabolic stability over curcumin,
      could exhibit anti-inflammatory activity in murine and human lymphocytes. Both
      curcumin and DiMC suppressed mitogen as well as antigen driven proliferation of
      murine splenic lymphocytes. Further, mitogen and antigen-stimulated cytokine (IL
      2, IL-4, IL-6 and IFN-gamma) secretion by T cells was also abrogated by curcumin
      and DiMC. Interestingly, curcumin and DiMC suppressed B cell proliferation
      induced by lipopolysaccharide. Curcumin and DiMC also inhibited Con A-induced
      activation of early and late T cell activation markers. They scavenged basal
      reactive oxygen species and depleted GSH levels in lymphocytes. The suppression
      of mitogen-induced T cell proliferation and cytokine secretion by curcumin and
      DiMC was significantly abrogated by thiol containing antioxidants suggesting a
      role for redox in their anti-inflammatory activity. Further, the possibility of
      curcumin and DiMC directly interacting with thiol-containing antioxidant GSH was
      monitored by changes in absorbance. Both curcumin and DiMC inhibited Con A
      induced activation of NF-kappaB and MAPK. More importantly, curcumin and DiMC
      inhibited phytohaemagglutinin induced proliferation and cytokine secretion by
      human peripheral blood mononuclear cells. To explore their therapeutic efficacy,
      they were added to lymphocytes post-Con A stimulation and we observed a
      significant suppression of IL-2, IL-6 and IFN-gamma. The present study for the
      first time demonstrates the potent anti-inflammatory activity of DiMC. Further,
      DiMC could find application as an alternative to curcumin, which is currently
      used in several clinical studies, due to its superior bioavailability and
      comparable efficacy.

PMID- 21726544
TI  - ChREBP gene polymorphisms are associated with coronary artery disease in Han
      population of Hubei province.
AB  - BACKGROUND: ChREBP regulates lipogenesis and glucose utilization in the liver.
      Current reports suggest a contradictive association between rs3812316 of this
      gene and triglyceride level. We hypothesized the polymorphisms in ChREBP gene
      were associated with CAD in Chinese population. METHODS: The ChREBP gene
      polymorphisms were analyzed by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) methods in 200 controls and 310 CAD patients.
      Serum lipids and glucose concentrations were measured in all subjects. Haplotypes
      were constructed based on rs3812316, rs7798357 and rs1051921. All the data were
      analyzed using SPSS14.0, PLINK1.07 and SHEsis software. RESULTS: The rare allele
      G of rs3812316 was significantly lower in the CAD group after adjusting for age,
      sex, BMI, SBP and DBP (OR(a)=0.589, 95%CI=0.361-0.961, P=0.034). No significant
      differences between cases and controls were found in genotype or allele
      distributions of rs7798357, rs17145750 and rs1051921. Haplotype CGC was
      significant higher in CAD group (P<0.01, OR=2.364, 95%CI=1.608-3.474), while
      haplotypes GGC, CGT, CCC were significant lower in CAD group (P<0.05).
      CONCLUSIONS: The rs3812316 and the haplotypes in ChREBP gene appeared to be
      related to high susceptibility to CAD.

PMID- 21726545
TI  - Serum amylase and risk of the metabolic syndrome in Korean adults.
AB  - BACKGROUND: Serum amylase has recently been shown to be associated with ghrelin
      and adiponectin as well as obesity. We investigated the relationship between
      total amylase and metabolic syndrome in adults. METHODS: 4495 adults were
      enrolled. All subjects denied any medical history or status of a disorder that
      could influence their serum amylase. Anthropometry, metabolic risk factors and
      total amylase concentration were measured. Each participant was categorized into
      one of 4 subgroups according to their total amylase concentration. Multiple
      logistic regression analysis was used to assess the independent association
      between amylase concentration and metabolic syndrome. Receiver-operating
      characteristics (ROC) curves analyses were used for comparison of the diagnostic
      value of amylase and other biomarkers for metabolic syndrome. RESULTS: The
      prevalence of metabolic syndrome by the National Cholesterol Education Program
      criteria was 13.4%, 15.3%, 19.3%, and 24.2% of those in the fourth, third,
      second, and lowest quartile of amylase concentration (P for trend <0.001). After
      adjusting for age, sex, and body mass index, the odds ratios of the lower
      quartiles were significantly higher compared to the fourth quartile for the
      presence of metabolic syndrome. In ROC curve analysis, amylase was similar to
      uric acid as a significant diagnostic indicator for metabolic syndrome, but it
      had lower diagnostic value than alanine aminotransferase, gamma
      glutamyltransferase or C-reactive protein. CONCLUSIONS: Lower amylase
      concentration is associated with an increased prevalence of metabolic syndrome.
      Amylase may contribute to identifying metabolic syndrome, although further
      research is needed to understand the mechanism behind these associations.

PMID- 21726546
TI  - Evolution and development of polarized germ cell cysts: new insights from a
      polychaete worm, Ophryotrocha labronica.
AB  - Polarized oogenic cysts are clonal syncytia of germ cells in which some of the
      sister cells (cystocytes) differentiate not as oocytes, but instead as nurse
      cells: polyploid cells that support oocyte development. The intricate machinery
      required to establish and maintain divergent cell fates within a syncytium, and
      the importance of associated oocyte patterning for subsequent embryonic
      development, have made polarized cysts valuable subjects of study in
      developmental and cell biology. Nurse cell/oocyte specification is best
      understood in insects, particularly Drosophila melanogaster. However, polarized
      cysts have evolved independently in several other animal phyla. We describe the
      differentiation of female cystocytes in an annelid worm, the polychaete
      Ophryotrocha labronica. These worms are remarkable for their elegantly simple
      cysts, which comprise a single oocyte and nurse cell, making them an appealing
      complement to insects as subjects of study. To elucidate the process of cystocyte
      differentiation in O. labronica, we have constructed digital 3D models from
      electron micrographs of serially sectioned ovarian tissue. These models show that
      2-cell cysts arise by fragmentation of larger "parental" cysts, rather than as
      independent units. The parental cysts vary in size and organization, are produced
      by asynchronous, indeterminate mitotic divisions of progenitor cystoblasts, and
      lack fusome-like organizing organelles. All of these characteristics represent
      key cytological differences from "typical" cyst development in insects like D.
      melanogaster. In light of such differences and the plasticity of female cyst
      structure among other animals, we suggest that it is time to reassess common
      views on the conservation of oogenic cysts and the importance of cysts in animal
      oogenesis generally.

PMID- 21726547
TI  - Shroom3 and a Pitx2-N-cadherin pathway function cooperatively to generate
      asymmetric cell shape changes during gut morphogenesis.
AB  - The cytoskeletal protein Shroom3 is a potent inducer of epithelial cell shape
      change and is required for lens and neural plate morphogenesis. Analysis of gut
      morphogenesis in Shroom3 deficient mouse embryos revealed that the direction of
      gut rotation is also disrupted. It was recently established that Pitx2-dependent,
      asymmetrical cellular behaviors in the dorsal mesentery (DM) of the early mid
      gut, a structure connecting the gut-tube to the rest of the embryo, contribute to
      the direction of gut rotation in chicken embryos by influencing the direction of
      the dorsal mesenteric tilt. Asymmetric cell shapes in the DM epithelium are
      hypothesized to contribute to the tilt, however, it is unclear what lies
      downstream of Pitx2 to alter epithelial cell shape. The cells of the left DM
      epithelium in either Pitx2 or Shroom3 deficient embryos are shorter and wider
      than those in control embryos and resemble the shape of those on the right,
      demonstrating that like Pitx2, Shroom3 is required for cell shape asymmetry and
      the leftward DM tilt. Because N-cadherin expression is specific to the left side
      and is Pitx2 dependent, we determined whether Shroom3 and N-cadherin function
      together to regulate cell shape in the left DM epithelium. Analysis of mouse
      embryos lacking one allele of both Shroom3 and N-cadherin revealed that they
      possess shorter and wider left epithelial DM cells when compared with Shroom3 or
      N-cadherin heterozygous embryos. This indicates a genetic interaction. Together
      these data provide evidence that Shroom3 and N-cadherin function cooperatively
      downstream of Pitx2 to directly regulate cell shape changes necessary for early
      gut tube morphogenesis.

PMID- 21726548
TI  - The Hem protein mediates neuronal migration by inhibiting WAVE degradation and
      functions opposite of Abelson tyrosine kinase.
AB  - In the nervous system, neurons form in different regions, then they migrate and
      occupy specific positions. We have previously shown that RP2/sib, a well-studied
      neuronal pair in the Drosophila ventral nerve cord (VNC), has a complex migration
      route. Here, we show that the Hem protein, via the WAVE complex, regulates
      migration of GMC-1 and its progeny RP2 neuron. In Hem or WAVE mutants, RP2 neuron
      either abnormally migrates, crossing the midline from one hemisegment to the
      contralateral hemisegment, or does not migrate at al and fail to send out its
      axon projection. We report that Hem regulates neuronal migration through
      stabilizing WAVE. Since Hem and WAVE normally form a complex, our data argues
      that in the absence of Hem, WAVE, which is presumably no longer in a complex,
      becomes susceptible to degradation. We also find that Abelson tyrosine kinase
      affects RP2 migration in a similar manner as Hem and WAVE, and appears to operate
      via WAVE. However, while Abl negatively regulates the levels of WAVE, it
      regulates migration via regulating the activity of WAVE. Our results also show
      that during the degradation of WAVE, Hem function is opposite to that of and
      downstream of Abl.

PMID- 21726549
TI  - Anti-diabetic effects of pentamethylquercetin in neonatally streptozotocin
      induced diabetic rats.
AB  - Pentamethylquercetin (PMQ), a methylated quercetin derivative, was screened for
      anti-diabetic effects in neonatally streptozotocin (STZ)-induced diabetic rats (n
      STZ diabetic rats). Streptozotocin (90 mg/kg) was administered intraperitoneally
      to 2-day-old male pups to induce diabetes. PMQ was administered at doses of 2.5,
      5, 10 and 20mg/kg/day orally when the rats were 6 weeks old and continued for 10
      consecutive weeks. Body weights were followed. Fasting and fed glucose,
      triglyceride and insulin levels were monitored periodically at the 6th and 10th
      week after PMQ treatment. At the end of the study, oral glucose tolerance test
      was performed, and kidney and liver function parameters were assayed. It was
      found that PMQ intervention dose-dependently reduced postprandial glucose and
      triglyceride levels, prevented the onset of overt diabetes, ameliorated
      polydipsia symptom induced by diabetes, attenuated glucose intolerance, enhanced
      insulin sensitivity indices and decreased endogenous creatinine clearance rate,
      urinary albumin excretion rate and blood alanine aminotransferase levels of n-STZ
      diabetic rats in comparison to their diabetic counterparts. The results from the
      present study thus suggest that PMQ exhibits great potential as an antidiabetic
      agent by improving hyperglycemia and reducing the incidence of peripheral
      complications.

PMID- 21726550
TI  - A C-terminal PDZ binding domain modulates the function and localization of Kv1.3
      channels.
AB  - The voltage-gated potassium channel, Kv1.3, plays an important role in regulating
      membrane excitability in diverse cell types ranging from T-lymphocytes to
      neurons. In the present study, we test the hypothesis that the C-terminal PDZ
      binding domain modulates the function and localization of Kv1.3. We created a
      mutant form of Kv1.3 that lacked the last three amino acids of the C-terminal PDZ
      binding domain (Kv1.3DeltaTDV). This form of Kv1.3 did not bind the PDZ domain
      containing protein, PSD95. We transfected wild type and mutant Kv1.3 into HEK293
      cells and determined if the mutation affected current, Golgi localization, and
      surface expression of the channel. We found that cells transfected with
      Kv1.3DeltaTDV had greater current and lower Golgi localization than those
      transfected with Kv1.3. Truncation of the C-terminal PDZ domain did not affect
      surface expression of Kv1.3. These findings suggest that PDZ-dependent
      interactions affect both Kv1.3 localization and function. The finding that
      current and Golgi localization changed without a corresponding change in surface
      expression suggests that PDZ interactions affect localization and function via
      independent mechanisms.

PMID- 21726551
TI  - Heritability of ocular component dimensions in mice phenotyped using depth
      enhanced swept source optical coherence tomography.
AB  - The range of genetic and genomic resources available makes the mouse a powerful
      model for the genetic dissection of complex traits. Because accurate, high
      throughput phenotypic characterisation is crucial to the success of such
      endeavours, we recently developed an optical coherence tomography (OCT) system
      with extended depth range scanning capability for measuring ocular component
      dimensions in mice. In order to test whether the accuracy and reproducibility of
      our OCT system was sufficient for gene mapping studies, we carried out an
      experiment designed to estimate the heritability of mouse ocular component
      dimensions. High-resolution, two dimensional tomograms were obtained for both
      eyes of 11 pairs of 8 week-old outbred MF1 mice. Subsequently, images were
      obtained when their offspring were aged 8 weeks. Biometric data were extracted
      after image segmentation, reconstruction of the geometric shape of each surface,
      and calculation of intraocular distances. The repeatability of measurements was
      evaluated for 12 mice scanned on consecutive days. Heritability estimates were
      calculated using variance components analysis. Sets of tomograms took ~2 s to
      acquire. Biometric data could be obtained for 98% of the 130 eyes scanned. The
      95% limits of repeatability ranged from +/-6 to +/-16 MUm for the axial ocular
      component dimensions. The heritability of the axial ocular components was 0.6
      0.8, except for corneal thickness, which had a heritability not significantly
      different from zero. In conclusion, axial ocular component dimensions are highly
      heritable in mice, as they are in humans. OCT with extended depth range scanning
      can be used to rapidly phenotype individual mice with sufficient accuracy and
      precision to permit gene mapping studies.

PMID- 21726552
TI  - An NGF mimetic, MIM-D3, stimulates conjunctival cell glycoconjugate secretion and
      demonstrates therapeutic efficacy in a rat model of dry eye.
AB  - The aim of this study was to evaluate the efficacy of MIM-D3, a small molecule
      nerve growth factor (NGF) peptidomimetic, as a therapeutic agent in rats with
      scopolamine induced dry eye. NGF plays an important role in ocular surface
      maintenance and corneal wound healing and was recently shown to have mucin
      secretagogue activity in conjunctival cells. We investigated whether MIM-D3
      increased glycoconjugate secretion in conjunctival cells in vitro and in rat tear
      fluids in vivo. Primary rat conjunctival cell cultures were treated with
      increasing concentrations of MIM-D3 and evaluated for glycoconjugate secretion,
      proliferation and MAPK1/2 activation. Glycoconjugates were quantitated in tear
      fluids from normal rats treated topically with increasing doses of MIM-D3 (0.4%,
      1% and 2.5%). Dry eye was induced in rats by subcutaneous scopolamine treatment,
      administered by surgically implanted osmotic pumps for 14 or 28 days. Aqueous
      tear production, tear clearance, fluorescein corneal staining and tear break-up
      time (tBUT) were evaluated. Glycoconjugates and NGF were quantitated in the tear
      fluids by enzyme-linked lectin assay (ELLA) and enzyme-linked immunosorbant assay
      (ELISA), respectively. We found that 50 MUM MIM-D3 statistically significantly
      induced a 1.3-fold increase in glycoconjugate secretion and a 2.3-fold increase
      in MAPK1/2 activation without increasing proliferation from conjunctival cell
      cultures. Application of 2.5% MIM-D3 in normal rat eyes statistically
      significantly increased tear glycoconjugate concentration by 2.3-fold. In the
      experimental dry eye model, application of 1% MIM-D3 to rat eyes for either 1 or
      17 consecutive days, followed by 1 week of no dosing produced a statistically
      significant decrease in corneal staining (p < 0.001), a slight increase in tBUT,
      and increases in tear glycoconjugates (p < 0.05) compared to vehicle. Scopolamine
      treatment also caused a statistically significant increase of endogenous NGF in
      tears (p < 0.005). We concluded that the increase in glycoconjugate concentration
      by the 1% MIM-D3 dose may have improved the quality and stability of the tear
      film, and thereby improved healing on the ocular surface in dry eye. Therefore,
      MIM-D3 may have therapeutic potential as a topical agent for the treatment of dry
      eye.

PMID- 21726553
TI  - Longitudinal functional magnetic resonance imaging of cognition in preclinical
      Huntington's disease.
AB  - Neuropsychological and functional neuroimaging studies have revealed early
      changes of cognition and brain function in individuals with the Huntington's
      disease (HD) gene mutation who are presymptomatic for the motor symptoms of the
      disease (preHD). However, little is known about whether changes of neural
      function progress over time. In this study, we used neuropsychological tests of
      attention, working memory and executive function, functional magnetic resonance
      imaging and voxel-based analyses of high-resolution structural data to explore
      the temporal dynamics of potential cognitive, functional and structural
      biomarkers in far from onset preHD (n=13, mean time to the estimated motor
      symptom onset=19.5 years) and healthy controls (n=13) followed over a 2-year
      period. Behavioral measures were similar in preHD individuals and controls at
      baseline and remained normal 2 years later. At both time points, the left
      dorsolateral prefrontal cortex was less active in preHD than in controls during
      working memory performance. The left dorsolateral prefrontal cortex did not
      exhibit further loss of activity over time. Regions showing less gray matter
      volume in preHD at baseline did not show further volume loss over time. These
      data indicate that the activity in brain regions contributing to working memory
      processing differs consistently in HD expansion mutation carriers while cognitive
      performance remains normal. However, the present data do not support the notion
      of a progressive decline of left prefrontal cortex activity in far from onset
      preHD followed over a 2-year period.

PMID- 21726554
TI  - Deep brain stimulation of the subthalamic nucleus transiently enhances loss
      chasing behaviour in patients with Parkinson's disease.
AB  - Dopaminergic treatments are associated with impulse control disorders such as
      pathological gambling in a subset of patients with Parkinson's Disease. While
      deep brain stimulation of the subthalamic nucleus has been reported to reduce
      symptoms of impulse control disorders in some Parkinson's Disease patients,
      little is known about its specific effects on gambling behaviour. In this
      experiment, we investigated the effects of deep brain stimulation of the
      subthalamic nucleus on one of the central features of pathological gambling: the
      tendency to chase losses. Loss-chasing is associated with impaired control over
      gambling behaviour and it is one of the most salient features of pathological
      gambling as it presents in the clinic. Twenty two patients with advanced
      idiopathic Parkinson's Disease and chronically implanted subthalamic nucleus
      electrodes for deep brain stimulation completed a simple laboratory model of loss
      chasing behaviour twice: once with and once without stimulation. Exploratory
      analysis indicated that deep brain stimulation of the subthalamic nucleus
      increased the value of losses chased by patients with Parkinson's Disease when
      shifting from off- to on-stimulation. These effects were not attributable to
      changes in state affect or to the motor impairments produced by the withdrawal of
      deep brain stimulation of the subthalamic nucleus. The effects of the stimulation
      on the value of losses chased were more pronounced in female than in male
      patients and reduced in patients taking dopamine receptor agonists. Collectively,
      these results suggest that deep brain stimulation of the subthalamic nucleus can
      transiently alter the evaluation of accumulated losses during gambling episodes
      in idiopathic Parkinson's Disease.

PMID- 21726555
TI  - Recovery of primary sporocysts in vivo in the Schistosoma mansoni/Biomphalaria
      glabrata model using a simple fixation method suitable for extraction of genomic
      DNA and RNA.
AB  - Detailed studies of host/parasite interactions are currently limited because in
      situ gene sequencing or monitoring of parasite gene expression is so far limited
      to genes presenting a high loci copy number in the Schistosome genome or a high
      level of expression. Indeed, how to investigate the host parasite molecular
      interplay when parasites are not directly accessible in vivo? Here we describe a
      method to circumvent this problem and to analyze DNA and RNA of Schistosoma
      mansoni during the interaction with its intermediate snail host Biomphalaria
      glabrata. We propose a technique for improved DNA and RNA extraction from the
      intra-molluscan stage of the parasite recovered after fixation of infected snails
      in Raillet-Henry solution. The extractions can be used for genetic analysis,
      transcription studies and microsatellite genotyping.

PMID- 21726556
TI  - The emerging role of Mule and ARF in the regulation of base excision repair.
AB  - The ARF (Alternative Reading Frame) protein is encoded in the Ink4a locus of
      human chromosome 9 that is frequently mutated in cancer cells. It was recently
      demonstrated that ARF is induced in response to DNA damage and inhibits, by
      direct interaction, the E3 ubiquitin ligase Mule that regulates p53 protein
      levels. Mule inhibition leads to p53 accumulation and activates cellular DNA
      damage responses. Mule has also recently been identified as a major E3 ubiquitin
      ligase involved in the regulation of DNA base excision repair. In this review, we
      will summarise the major properties of Mule and ARF and their roles in the
      coordination of DNA repair and DNA replication.

PMID- 21726557
TI  - FSH acts on the proliferation of type A spermatogonia via Nur77 that increases
      GDNF expression in the Sertoli cells.
AB  - The molecular mechanism responsible for the regulation of GDNF in Sertoli cells
      remains largely unknown. In the present study, FSH induced the expression of
      Nur77 and GDNF in mouse testis tissue and human fetal Sertoli cells. Moreover,
      FSH increased the number of A spermatogonia co-cultured with Sertoli cells. In
      the additional assays, Nur77 was observed to directly regulate GDNF
      transcription. Furthermore, overexpression of Nur77 and siRNA-mediated knockdown
      of Nur77 affected levels of GDNF mRNA and protein in primary human fetal Sertoli
      cells. These results indicate that FSH-induced Nur77 regulates the expression of
      GDNF in Sertoli cells to stimulate the proliferation of A spermatogonia in vitro.

PMID- 21726558
TI  - Rising fecal glucocorticoid concentrations track reproductive activity in the
      female giant panda (Ailuropoda melanoleuca).
AB  - To better understand the adaptive significance of adrenal glucocorticoid (GC)
      variation in the giant panda, we assessed patterns of fecal GC excretion over
      time as well as during estrus, parturient and non-parturient luteal phases,
      lactation and acyclicity in 17 adult females. Fecal estrogen and GC patterns were
      positively correlated (P<0.05) in four of five periestrual females (r = 0.57
      0.92). Among all reproductive states, fecal GC was highest (P<0.05) during
      periestrus (non-parturient, 495.9 +/- 100.7 ng/g [mean +/- SE]; parturient, 654.1
      +/- 10 6.5 ng/g; P>0.05). Concentrations of GC metabolites were lower (P<0.05)
      during the later stage of the luteal phase in non-parturient (334.8 +/- 24.8
      ng/g) compared to parturient (470.4 +/- 54.0 ng/g) females. Although fecal GC
      concentrations in cyclic, non-parturient females did not differ (P>0.05) across
      all seasons, there were seasonal variations (P<0.05) in females that were acyclic
      and non-lactational. However, the overall lack of difference (P>0.05) in GC
      values between reproductively cyclic and acyclic females did not support the
      hypothesis that ovarian acyclicity is due to increased adrenal activity (related
      or unrelated to physiological stress). Furthermore, GCs may play an important
      role in the normal endocrine milieu associated with sexual receptivity and late
      pregnancy. These data demonstrate that both reproductive status and seasonal
      factors are important modulators of adrenal function in this endangered species.

PMID- 21726559
TI  - RpL10A regulates oogenesis progression in the banana prawn Fenneropenaeus
      merguiensis and Drosophila melanogaster.
AB  - To develop banana prawn (Fenneropenaeus merguiensis) aquaculture, the mechanism
      of ovarian maturation is under investigation. In a previous study, we reported
      the RpL10A protein as an ovarian maturation stimulator. To further investigate
      the function of RpL10A, we turned to the fruit fly (Drosophila melanogaster) to
      take advantage of the genetic tools available. Here, we elucidate the expression
      and function of RpL10A in the D. melanogaster ovary. RpL10A is expressed in the
      cytoplasm of both nurse and follicle cells throughout oogenesis. While shrimp
      have one RpL10A gene, D. melanogaster has two genes, RpL10Aa and RpL10Ab. RpL10Ab
      displays more similarity with shrimp RpL10A and was further investigated. RpL10Ab
      homozygous mutants are lethal and germline clone analysis showed that RpL10Ab is
      an essential gene in oogenesis. Moreover, RpL10Ab(-) germline clones resulted in
      premature death of the follicle cells. This phenotype is reminiscent of some
      insulin pathway mutants, suggesting that RpL10Ab may be involved in the insulin
      signaling pathway. In addition, RpL10Ab(-) follicle cells showed abnormal nuclei
      and membranes. Shrimp RpL10A rescued RpL10Ab homozygous mutants, revealing their
      functional conservation. Surprisingly, we found cell death in multiple tissues
      when RpL10A was over-expressed, suggesting that proper RpL10A levels are
      important. This research reveals novel findings about the role of RpL10A during
      oogenesis and may, in the future, lead to new approaches to stimulate ovarian
      development in shrimp.

PMID- 21726560
TI  - New insights into the signaling system and function of insulin in fish.
AB  - Fish have provided essential information about the structure, biosynthesis,
      evolution, and function of insulin (INS) as well as about the structure,
      evolution, and mechanism of action of insulin receptors (IR). INS, insulin-like
      growth factor (IGF)-1, and IGF-2 share a common ancestor; INS and a single IGF
      occur in Agnathans, whereas INS and distinct IGF-1 and IGF-2s appear in
      Chondrichthyes. Some but not all teleost fish possess multiple INS genes, but it
      is not clear if they arose from a common gene duplication event or from multiple
      separate gene duplications. INS is produced by the endocrine pancreas of fish as
      well as by several other tissues, including brain, pituitary, gastrointestinal
      tract, and adipose tissue. INS regulates various aspects of feeding, growth,
      development, and intermediary metabolism in fish. The actions of INS are mediated
      through the insulin receptor (IR), a member of the receptor tyrosine kinase
      family. IRs are widely distributed in peripheral tissues of fish, and multiple IR
      subtypes that derive from distinct mRNAs have been described. The IRs of fish
      link to several cellular effector systems, including the ERK and IRS-PI3k-Akt
      pathways. The diverse effects of INS can be modulated by altering the production
      and release of INS as well as by adjusting the production/surface expression of
      IR. The diverse actions of INS in fish as well as the diverse nature of the
      neural, hormonal, and environmental factors known to affect the INS signaling
      system reflects the various life history patterns that have evolved to enable
      fish to occupy a wide range of aquatic habitats.

PMID- 21726561
TI  - Comparison of detection methods for cell surface globotriaosylceramide.
AB  - The cell surface-expressed glycosphingolipid (GSL), globotriaosylceramide
      (Gb(3)), is becoming increasingly important and is widely studied in the areas of
      verotoxin (VT)-mediated cytotoxicity, human immunodeficiency virus (HIV)
      infection, immunology and cancer. However, despite its diverse roles and
      implications, an optimized detection method for cell surface Gb(3) has not been
      determined. GSLs are differentially organized in the plasma membrane which can
      affect their availability for protein binding. To examine various detection
      methods for cell surface Gb(3), we compared four reagents for use in flow
      cytometry analysis. A natural ligand (VT1B) and three different monoclonal
      antibodies (mAbs) were optimized and tested on various human cell lines for Gb(3)
      detection. A differential detection pattern of cell surface Gb(3) expression,
      which was influenced by the choice of reagent, was observed. Two mAb were found
      to be suboptimal. However, two other methods were found to be useful as defined
      by their high percentage of positivity and mean fluorescence intensity (MFI)
      values. Rat IgM anti-Gb(3) mAb (clone 38-13) using phycoerythrin-conjugated
      secondary antibody was found to be the most specific detection method while the
      use of VT1B conjugated to Alexa488 fluorochrome was found to be the most
      sensitive; showing a rare crossreactivity only when Gb(4) expression was highly
      elevated. The findings of this study demonstrate the variability in detection of
      Gb(3) depending on the reagent and cell target used and emphasize the importance
      of selecting an optimal methodology in studies for the detection of cell surface
      expression of Gb(3).

PMID- 21726562
TI  - Development of sandwich ELISA for detection and quantification of human and
      murine a disintegrin and metalloproteinase17.
AB  - ADAM17 (a disintegrin and metalloproteinase-containing protein 17) is a membrane
      bound metalloproteinase, implicates in many physiological processes, including
      cell migration and proliferation. Of particular note, most of the studies so far
      are restricted on the analysis of ADAM17 mRNA levels. In this study we generated,
      utilizing hybridoma technology, three monoclonal antibodies (mAbs) (A 300, A 309
      and A 318) against the extracellular domain of human ADAM17 to enable
      quantification of protein expression. The specificity of these mAbs against
      ADAM17 was tested by enzyme-linked immunoadsorbent assay (ELISA), flourescence
      activated cell sorting (FACS) and western blotting. In order to quantify human
      and murine ADAM17 expression two pairs of these mAbs (biotinylated A 309 in
      combination with A 300 and biotinylated A 300 in combination with A 318), were
      used to develop sandwich ELISA. A panel of monoclonal antibodies was generated
      for first time to measure mouse ADAM17 with a sensitivty of 2 ng/ml. Such systems
      provide a useful tool to quantify protein levels of ADAM17 and are valuable tools
      for diagnostic purposes.

PMID- 21726563
TI  - A phloem-sap feeder mixes phloem and xylem sap to regulate osmotic potential.
AB  - Phloem-sap feeders (Hemiptera) occasionally consume the dilute sap of xylem, a
      behaviour that has previously been associated with replenishing water balance
      following dehydration. However, a recent study reported that non-dehydrated
      aphids ingested xylem sap. Here, we tested the hypothesis that the consumption of
      xylem sap, which has a low osmolality, is a general response to osmotic stresses
      other than dehydration. Alate aphids were subjected to different treatments and
      subsequently transferred onto a plant, where electrical penetration graph (EPG)
      was used to estimate durations of passive phloem sap consumption and active
      sucking of xylem sap. The proportion of time aphids fed on xylem sap (i.e., time
      spent feeding on xylem sap/total time spent feeding on phloem plus xylem sap) was
      used as a proxy of the solute concentration of the uptake. The proportion of time
      alate aphids fed on xylem sap increased: (1) with the time spent imbibing an
      artificial diet containing a solution of sucrose, which is highly concentrated in
      phloem sap and is mainly responsible for the high osmotic potential of phloem
      sap; (2) with the osmotic potential of the artificial diet, when osmotic
      potential excess was not related to sucrose concentration; and (3) when aphids
      were deprived of primary symbionts, a condition previously shown to lead to a
      higher haemolymph osmotic potential. All our results converge to support the
      hypothesis that xylem sap consumption contributes to the regulation of the
      osmotic potential in phloem-sap feeders.

PMID- 21726565
TI  - The neurodegenerative-disease-related protein sacsin is a molecular chaperone.
AB  - Various human neurodegenerative disorders are associated with processes that
      involve misfolding of polypeptide chains. These so-called protein misfolding
      disorders include Alzheimer's and Parkinson's diseases and an increasing number
      of inherited syndromes that affect neurons involved in motor control circuits
      throughout the central nervous system. The reasons behind the particular
      susceptibility of neurons to misfolded proteins are currently not known. The main
      function of a class of proteins known as molecular chaperones is to prevent
      protein misfolding and aggregation. Although neuronal cells contain the major
      known classes of molecular chaperones, central-nervous-system-specific chaperones
      that maintain the neuronal proteome free from misfolded proteins are not well
      defined. In this study, we assign a novel molecular chaperone activity to the
      protein sacsin responsible for autosomal recessive spastic ataxia of Charlevoix
      Saguenay, a degenerative disorder of the cerebellum and spinal cord. Using
      purified components, we demonstrate that a region of sacsin that contains a
      segment with homology to the molecular chaperone Hsp90 is able to enhance the
      refolding efficiency of the model client protein firefly luciferase. We show that
      this region of sacsin is highly capable of maintaining client polypeptides in
      soluble folding-competent states. Furthermore, we demonstrate that sacsin can
      efficiently cooperate with members of the Hsp70 chaperone family to increase the
      yields of correctly folded client proteins. Thus, we have identified a novel
      chaperone directly involved in a human neurodegenerative disorder.

PMID- 21726564
TI  - Two-step aminoacylation of tRNA without channeling in Archaea.
AB  - Catalysis of sequential reactions is often envisaged to occur by channeling of
      substrate between enzyme active sites without release into bulk solvent. However,
      while there are compelling physiological rationales for direct substrate
      transfer, proper experimental support for the hypothesis is often lacking,
      particularly for metabolic pathways involving RNA. Here, we apply transient
      kinetics approaches developed to study channeling in bienzyme complexes to an
      archaeal protein synthesis pathway featuring the misaminoacylated tRNA
      intermediate Glu-tRNA(Gln). Experimental and computational elucidation of a
      kinetic and thermodynamic framework for two-step cognate Gln-tRNA(Gln) synthesis
      demonstrates that the misacylating aminoacyl-tRNA synthetase (GluRS(ND)) and the
      tRNA-dependent amidotransferase (GatDE) function sequentially without channeling.
      Instead, rapid processing of the misacylated tRNA intermediate by GatDE and
      preferential elongation factor binding to the cognate Gln-tRNA(Gln) together
      permit accurate protein synthesis without formation of a binary protein-protein
      complex between GluRS(ND) and GatDE. These findings establish an alternate
      paradigm for protein quality control via two-step pathways for cognate aminoacyl
      tRNA formation.

PMID- 21726566
TI  - Crystal structure of the eukaryotic light-driven proton-pumping rhodopsin,
      Acetabularia rhodopsin II, from marine alga.
AB  - Acetabularia rhodopsin (AR) is a rhodopsin from the marine plant Acetabularia
      acetabulum. The opsin-encoding gene from A. acetabulum, ARII, was cloned and
      found to be novel but homologous to that reported previously. ARII is a light
      driven proton pump, as demonstrated by the existence of a photo-induced current
      through Xenopus oocytes expressing ARII. The photochemical reaction of ARII
      prepared by cell-free protein synthesis was similar to that of bacteriorhodopsin
      (BR), except for the lack of light-dark adaptation and the different proton
      release and uptake sequence. The crystal structure determined at 3.2 A resolution
      is the first structure of a eukaryotic member of the microbial rhodopsin family.
      The structure of ARII is similar to that of BR. From the cytoplasmic side to the
      extracellular side of the proton transfer pathway in ARII, Asp92, a Schiff base,
      Asp207, Asp81, Arg78, Glu199, and Ser189 are arranged in positions similar to
      those of the corresponding residues directly involved in proton transfer by BR.
      The side-chain carboxyl group of Asp92 appears to interact with the sulfhydryl
      group of Cys218, which is unique to ARII and corresponds to Leu223 of BR and to
      Asp217 of Anabaena sensory rhodopsin. The orientation of the Arg78 side chain is
      opposite to the corresponding Arg82 of BR. The putative absence of water
      molecules around Glu199 and Arg78 may disrupt the formation of the low-barrier
      hydrogen bond at Glu199, resulting in the "late proton release".

PMID- 21726568
TI  - Inactivation of EphA2 promotes tight junction formation and impairs angiogenesis
      in brain endothelial cells.
AB  - Eph receptor tyrosine kinases and ephrin ligands participate in the regulation of
      a wide variety of biological processes, such as axon guidance, synaptic
      plasticity, angiogenesis, and tumorigenesis. The role of Eph receptors and ephrin
      ligands in brain endothelial cells remains unknown. Here, we examined the
      expression profile of EphA receptors and ephrin-A ligands in human brain
      microvascular endothelial cell line (HBMEC). Our results showed that multiple
      EphA receptors and ephrin-A ligands are expressed in HBMEC. We found that the
      phosphorylation of EphA2, but not other EphA receptors, was significantly
      increased in HBMEC treated with recombinant ephrin-A1/Fc. Meanwhile, elevated
      EphA2 phosphorylation was accompanied by disassembly of tight junctions in HBMEC.
      Furthermore, EphA2 RNAi in HBMEC could promote tight junction formation and
      prevent the ephrin-A1-induced tight junction disruption. Also, when a kinase
      inactive mutant of EphA2 (EphA2-K646M) was expressed in HBMEC, the tight junction
      was enhanced and the ephrin-A1-induced tight junction disruption was blocked. In
      addition, EphA2 RNAi and expression of EphA2-K646M in HBMEC inhibited in vitro
      cell migration and angiogenesis of HBMEC. These data indicated an important role
      of EphA2 in regulating both tight junction formation and angiogenesis in brain
      endothelial cells.

PMID- 21726567
TI  - Multiple factors insulate Msh2-Msh6 mismatch repair activity from defects in Msh2
      domain I.
AB  - DNA mismatch repair (MMR) is a highly conserved mutation avoidance mechanism that
      corrects DNA polymerase misincorporation errors. In initial steps in MMR, Msh2
      Msh6 binds mispairs and small insertion/deletion loops, and Msh2-Msh3 binds
      larger insertion/deletion loops. The msh2Delta1 mutation, which deletes the
      conserved DNA-binding domain I of Msh2, does not dramatically affect Msh2-Msh6
      dependent repair. In contrast, msh2Delta1 mutants show strong defects in Msh2
      Msh3 functions. Interestingly, several mutations identified in patients with
      hereditary non-polyposis colorectal cancer map to domain I of Msh2; none have
      been found in MSH3. To understand the role of Msh2 domain I in MMR, we examined
      the consequences of combining the msh2Delta1 mutation with mutations in two
      distinct regions of MSH6 and those that increase cellular mutational load (pol3
      01 and rad27). These experiments reveal msh2Delta1-specific phenotypes in Msh2
      Msh6 repair, with significant effects on mutation rates. In vitro assays
      demonstrate that msh2Delta1-Msh6 DNA binding is less specific for DNA mismatches
      and produces an altered footprint on a mismatch DNA substrate. Together, these
      results provide evidence that, in vivo, multiple factors insulate MMR from
      defects in domain I of Msh2 and provide insights into how mutations in Msh2
      domain I may cause hereditary non-polyposis colorectal cancer.

PMID- 21726570
TI  - The fastest (and simplest), the earliest: the locus of processing of rapid forms
      of motion aftereffect.
AB  - Adaptation to directional motion has been shown to bias the perceived direction
      of a subsequently presented stationary or flickering test stimulus toward the
      opposite direction with respect to that of adaptation. This phenomenon, called
      motion aftereffect, is usually generated with adaptation periods of tens of
      seconds or minutes and has been shown to depend upon the functional integrity of
      visual area V5/MT. Rapid forms of MAE, arising and decaying within half a second
      (rMAE), can also be generated with sub-second adaptation durations. In order to
      investigate the neural substrate underlying the rMAE, repetitive transcranial
      magnetic stimulation (rTMS) has been used just after the adaptation stimulus over
      areas V1/V2, V5/MT, or over the vertex. Results showed that, besides some
      reduction in strength of the rMAE when rTMS was delivered over V5/MT, it was
      maximally disrupted when stimulation was delivered over early visual areas V1/V2.
      This is the first study where a causal role of early visual cortices in MAE is
      demonstrated. Moreover, this finding supports the existence of multiple loci
      along the visual stream in which gain control takes place and generates the MAE
      as a byproduct. The specific locus is likely to depend on the specific stimulus
      used.

PMID- 21726571
TI  - Moderate noise induced cognition impairment of mice and its underlying
      mechanisms.
AB  - Noise pollution is recognized as a serious human health problem in modern
      society. The aim of the present study was to explore the effects of moderate
      intensity white noise exposure on learning and memory of mice, and the underlying
      mechanisms. The learning and memory ability of mice were evaluated by water maze
      and step-down inhibitory avoidance experiments respectively, following 1, 3, and
      6 weeks noise exposure (80 dB SPL, 2h/day). To explore potential mechanisms, we
      determined levels of oxidative stress in the inferior colliculus (IC), auditory
      cortex (AC), and hippocampus (the structures comprising the critical encephalic
      region associated with the acoustic lemniscal ascending pathway), the
      phosphorylation of microtubule-associated protein tau in the hippocampus
      (important role in learning and memory), and the basic auditory response
      properties of neurons in the IC. Moderate-intensity noise exposure impaired the
      learning and memory ability of mice in both water maze and step-down inhibitory
      avoidance experiments, and the longer the noise exposure time the greater the
      impairment. At 6 weeks after noise exposure, there was also evidence of oxidative
      damage in the IC, AC, and hippocampus, hyperphosphorylated tau protein in the
      hippocampus, and significant changes in the auditory response properties of
      neurons in the IC. These data results suggest that moderate-intensity noise can
      progressively impair the learning and memory ability of mice, which may result
      from peroxidative damage, tau hyperphosphorylation, and auditory coding
      alteration.

PMID- 21726572
TI  - Ammodytoxin: a window into understanding presynaptic toxicity of secreted
      phospholipases A(2) and more.

PMID- 21726569
TI  - Mouse pharmacological models of cognitive disruption relevant to schizophrenia.
AB  - Schizophrenia is a debilitating cognitive disorder. The link between cognitive
      debilitation and functional outcome in patients with schizophrenia has prompted
      research to develop procognitive therapies. It is hoped that by improving
      cognition in these patients, their functional outcome will also improve. Although
      no established treatments exist as yet, progress has been made toward
      understanding how to evaluate putative compounds in the clinic. Genetic mouse
      models and pharmacological rat models of cognitive disruption are being developed
      that may help to evaluate these putative compounds preclinically. Considering the
      increased number of genetic mouse models relevant to schizophrenia, there is a
      need to evaluate pharmacological manipulations on cognition in mice. Here we
      review the current literature on mouse pharmacological models relevant to
      schizophrenia. In this review, we discuss where different pharmacological effects
      between rats and mice on cognitive tasks are observed and assess the validity
      offered by these models. We conclude that the predictive validity of these models
      is currently difficult to assess and that much more needs to be done to develop
      useful mouse pharmacological models of cognitive disruption in schizophrenia.

PMID- 21726573
TI  - The role of NPY in hypothalamic mediated food intake.
AB  - Neuropeptide Y (NPY) is a highly conserved neuropeptide with orexigenic actions
      in discrete hypothalamic nuclei that plays a role in regulating energy
      homeostasis. NPY signals via a family of high affinity receptors that mediate the
      widespread actions of NPY in all hypothalamic nuclei. These actions are also
      subject to tight, intricate regulation by numerous peripheral and central energy
      balance signals. The NPY system is embedded within a densely-redundant network
      designed to ensure stable energy homeostasis. This redundancy may underlie
      compensation for the loss of NPY or its receptors in germline knockouts,
      explaining why conventional knockouts of NPY or its receptors rarely yield a
      marked phenotypic change. We discuss insights into the hypothalamic role of NPY
      from studies of its physiological actions, responses to genetic manipulations and
      interactions with other energy balance signals. We conclude that numerous
      approaches must be employed to effectively study different aspects of NPY action.

PMID- 21726574
TI  - Association between tryptophan hydroxylase-2 genotype and the antidepressant
      effect of citalopram and paroxetine on immobility time in the forced swim test in
      mice.
AB  - Tryptophan hydroxylase-2 (TPH2) is the rate limiting enzyme of serotonin
      synthesis in the brain. The 1473G allele of the C1473G polymorphism in mTPH2 gene
      is associated with reduced enzyme activity and serotonin synthesis rate in the
      mouse brain. Here, the influence of the 1473G allele on the antidepressant effect
      of selective serotonin reuptake inhibitors (SSRIs), citalopram (2.5 or 5.0mg/kg)
      and paroxetine (5.0 or 10.0mg/kg), in the forced swim test was studied using B6
      1473G and B6-1473C congenic mouse lines with the 1473G (decreased TPH2 activity)
      or 1473C (normal TPH2 activity) alleles, respectively, transferred to the genome
      of C57BL/6 mouse strain. Paroxetine (5.0 or 10.0mg/kg) and citalopram (2.5 or
      5.0mg/kg) decreased immobility time in B6-1473C mice, while both doses of
      paroxetine and 2.5mg/kg of citaloprame did not alter immobility time in B6-1473G
      mice. However, 5.0mg/kg of citalopram reduced immobility in B6-1473G mice. The
      results provided genetic evidence of moderate association between 1473G allele
      and reduced sensitivity to SSRIs in mice.

PMID- 21726575
TI  - Adverse childhood experiences and smoking status in five states.
AB  - OBJECTIVE: Our objective was to examine the associations between adverse
      childhood experiences (ACEs) and smoking behavior among a random sample of adults
      living in five U.S. states. METHODS: We used data from 25,809 participants of the
      2009 Behavioral Risk Factor Surveillance System to assess the relationship of
      each of the 8 adverse childhood experiences and the adverse childhood experience
      score to smoking status. RESULTS AND CONCLUSIONS: Some 59.4% of men and women
      reported at least one adverse childhood experience. Each of the eight adverse
      childhood experiences measures was significantly associated with smoking status
      after adjustment for demographic variables. The prevalence ratios for current and
      ever smoking increased in a positive graded fashion as the adverse childhood
      experience score increased. Among adults who reported no adverse childhood
      experiences, 13.0% were currently smoking and 38.3% had ever smoked. Compared to
      participants with an adverse childhood experience score of 0, those with an
      adverse childhood experience score of 5 or more were more likely to be a current
      smoker (adjusted prevalence ratio (aPR): 2.22, 95% confidence interval [CI]: 1.92
      2.57) and to have ever smoked (aPR: 1.80, 95% CI: 1.67-1.93). Further research is
      warranted to determine whether the prevention of and interventions for adverse
      childhood experiences might reduce the burden of smoking-related illness in the
      general population.

PMID- 21726577
TI  - Feasibility and efficacy of pairing fecal immunochemical testing with mammography
      for increasing colorectal cancer screening among uninsured Latinas in northern
      Manhattan.
AB  - OBJECTIVES: We evaluated the feasibility and efficacy of a program to promote
      colorectal cancer screening (CRC) among uninsured Latinas receiving mammography
      through a cancer screening clinic in northern Manhattan. METHODS: Between August
      2009 and March 2010, unscreened, average CRC risk, uninsured Latinas, aged 50-64
      years, undergoing mammography received a screening recommendation, education, and
      fecal immunochemical test (FIT). Socio-demographic information and level of
      acculturation was collected. Screening compliance was assessed. RESULTS: Of 651
      Latinas evaluated, 210 were eligible and, of these, 94% (n=197) consented to
      participate; 441 were excluded because they were up-to-date with CRC screening
      (n=130), < 50 (n=285) or >64 (n=26) years of age. After intervention, 177 (90%)
      completed FIT. Within 2 weeks, 87% completed the FIT, and 69% did so with no
      reminder calls. Acculturation was significantly lower among screeners (p=0.014).
      Compared with non-screeners, screeners were more likely to be foreign-born
      (p=0.009), to speak only Spanish (p=0.043), and to prefer to read (p=0.037), and
      think (p=0.015) in Spanish. CONCLUSION: This study suggests that pairing CRC
      education and screening with mammography is both feasible and efficacious.

PMID- 21726576
TI  - Do social inequalities in cervical cancer screening persist among patients who
      use primary care? The Paris Prevention in General Practice survey.
AB  - OBJECTIVE: Social inequalities in cervical cancer screening may be related to
      either lack of access to care or inadequate delivery of preventive care by
      providers. We sought to characterize social inequalities among women consulting
      general practitioners with a wide range of social position indicators. METHODS:
      In 2005-06, 59 randomly recruited general practitioners from the Paris
      metropolitan area enrolled every woman aged 50-69 years seen during a two-week
      period. Cervical cancer screening status (overdue if the last cervical cancer
      screening had been more than 3 years earlier) was analyzed for 858 women in a
      logistic mixed model that considered: occupational class (in 5 levels, based on
      last occupation), education, income, characteristics related to family, housing,
      neighborhood, household wealth (social allocations, perceived financial
      difficulties in 4 levels, income tax), employment status, supplementary health
      insurance, and social network (4 levels). RESULTS: The rate of overdue patients
      did not vary between general practitioners (21%). social position indicators
      associated with overdue status (odds ratio between 2 adjacent decreasing social
      levels) were occupational class (1.20, 95% CI: 1.03-1.41), social network (1.52,
      95% CI: 1.18-1.94), financial difficulties (1.42, 95% CI: 1.07-1.88),
      neighborhood safety (2.15, 95% CI: 1.10-4.20), and allocations (3.34, 95% CI:
      1.12-9.96). CONCLUSIONS: Even among women visiting general practitioners we
      observed marked social inequalities that persist above and beyond occupational
      class.

PMID- 21726578
TI  - Grouper (Epinephelus coioides) CXCR4 is expressed in response to pathogens
      infection and early stage of development.
AB  - Chemokine (C-X-C motif) receptor 4 (CXCR4) from orange-spotted grouper
      (Epinephelus coioides) was identified and characterized in this study. gCXCR4
      shared common features in protein sequence and predicted structure of CXCR4
      family. This suggested that gCXCR4 is a member of G protein-coupled receptors
      with seven transmembrane domains. The expression patterns revealed that gCXCR4
      may play a key role in early development of grouper. Furthermore, overexpression
      of gCXCR4-GFP for 48 h had significant effects on the GF-1 cell viability. gCXCR4
      protein was mainly expressed in the marginal zone of head kidney and on the
      surface of intestinal villi. gCXCR4 expression can be detected in all the
      examined tissues and significantly up-regulated in eye and brain, which are the
      main targets for nervous necrosis virus (NNV) infection and replication. gCXCR4
      gene expression can be induced in the spleen and eye by lipopolysaccharide and
      NNV, respectively. Our data suggested that gCXCR4 may not only play a role in the
      early immune response to microbial infection but also restrain to the immune
      system and central nervous system.

PMID- 21726579
TI  - Neonatal injections of methoxychlor decrease adult rat female reproductive
      behavior.
AB  - Methoxychlor (MXC), a commonly used pesticide, has been labeled as an endocrine
      disruptor. To evaluate the impact of neonatal exposure to MXC on female
      reproduction, female Sprague-Dawley rats were given subcutaneous injections on
      postnatal days 1, 3, and 5. The injections contained 1.0mg MXC, 2.0mg MXC, 10 MUg
      17beta-estradiol benzoate (positive control), or sesame oil (vehicle). The
      injections of MXC had no effect on anogenital distance or day of vaginal opening.
      Treatment with either 2.0mg MXC or estradiol significantly increased the total
      number of days with vaginal keratinization. Treatment with MXC had no effect on
      ability to exhibit a mating response as an adult female, although the high dose
      MXC (2.0) and the positive control (estradiol) animals demonstrated a decrease in
      degree of receptivity, a decrease in proceptive behavior and an increase in
      rejection behavior. These data suggest that higher doses of MXC given directly to
      pups during the neonatal period can act as an estrogen and alter aspects of the
      nervous system, impacting adult reproductive characteristics.

PMID- 21726580
TI  - A horizontal slice preparation for examining the functional connectivity of
      dorsal column fibres in mouse spinal cord.
AB  - In spinal cord injury (SCI) research, axon regeneration across spinal lesions is
      most often assessed using anatomical methods. It would be extremely advantageous,
      however, to examine the functional synaptic connectivity of regenerating fibres,
      using high-resolution electrophysiological methods. We have therefore developed a
      mouse horizontal spinal cord slice preparation that permits detailed analysis of
      evoked dorsal column (DCol) synaptic inputs on spinal neurons, using whole-cell
      patch clamp electrophysiology. This preparation allows us to characterise
      postsynaptic currents and potentials in response to electrical stimulation of
      DCol fibres, along with the intrinsic properties of spinal neurons. In addition,
      we demonstrate that low magnification calcium imaging can be used effectively to
      survey the spread of excitation from DCol stimulation in horizontal slices. This
      preparation is a potentially valuable tool for SCI research where confirmation of
      regenerated, functional synapses across a spinal lesion is critical.

PMID- 21726582
TI  - A two-culture method for exposure of human brain organotypic slice cultures to
      replicating human immunodeficiency virus type 1.
AB  - To evaluate the effect of HIV-1 virus on neural cells, we have developed a method
      to culture human fetal organotypic brain slices in the presence of live virus.
      Brain slices were placed on semipermeable hydrophilic membrane inserts, resting
      on top of wells that contain cultured H9 T-cells chronically producing HIV-1.
      This system allows free exposure of the brain slices to HIV-1, HIV-1 proteins,
      and other molecules released by the infected T-cells. After specific lengths of
      time in culture, slices were stained for viability with Calcein-AM and propidium
      iodide, for neural cell markers such as GFAP, nestin and beta-III-tubulin, tested
      for cell proliferation, and analyzed by fluorescent and confocal microscopy. When
      cultured in the presence of neural progenitor medium lacking serum, slices were
      viable and maintained active cell replication for at least 3 weeks in culture,
      without significant cell death. By comparison with slices co-cultured with
      uninfected T-cells or with medium alone, slices cultured in the presence of HIV-1
      showed increased nestin and GFAP. Moreover, in slices exposed to HIV-1-producing
      H9 cells, regions of nestin stain were, over time in culture, replaced with GFAP
      stain. This suggested the process of gliosis often found in brains of HIV-1
      infected individuals. This co-culture method can be used to model the dynamics
      and the microenvironment of brain tissue exposed to HIV-1 and can potentially be
      used to test therapies directed at preventing HIV-1-induced neural damage.

PMID- 21726583
TI  - Characterization of a fully human monoclonal antibody against extracellular
      domain of matrix protein 2 of influenza A virus.
AB  - The extra-cellular domain of the influenza virus matrix protein 2 (M2e) is highly
      conserved between influenza A virus strains compared to hemagglutinin and
      neuraminidase, and has long been viewed as a potential and universal vaccine
      target. M2e induces no or only weak and transient immune responses following
      infection, making it difficult to detect M2e-specific antibodies producing B
      cells in human peripheral blood lymphocytes. Recently, using a single-cell
      manipulation method, immunospot array assay on a chip (ISAAC), we obtained an M2e
      specific human antibody (Ab1-10) from the peripheral blood of a healthy
      volunteer. In this report, we have demonstrate that Ab1-10 reacted not only to
      seasonal influenza A viruses, but also to pandemic (H1N1) 2009 virus (2009 H1N1)
      and highly pathogenic avian influenza A virus, and that the antibody-bound M2e of
      2009 H1N1 inactivated the virus with high affinity (~10(-10)M). More importantly,
      it inhibited 2009 H1N1 viral propagation in vitro. These results suggest that Ab1
      10 might be a potential candidate for antibody therapeutics for a wide range of
      influenza A viruses.

PMID- 21726581
TI  - Long-term vascular access ports as a means of sedative administration in a rodent
      fMRI survival model.
AB  - The purpose of this study is to develop a rodent functional magnetic resonance
      imaging (fMRI) survival model with the use of heparin-coated vascular access
      devices. Such a model would ease the administration of sedative agents, reduce
      the number of animals required in survival experiments and eliminate animal-to
      animal variability seen in previous designs. Seven male Sprague-Dawley rats
      underwent surgical placement of an MRI-compatible vascular access port, followed
      by implantable electrode placement on the right median nerve. Functional MRI
      during nerve stimulation and resting-state functional connectivity MRI (fcMRI)
      were performed at times 0, 2, 4, 8 and 12 weeks postoperatively using a 9.4T
      scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed
      using atipamezole. There were no fatalities or infectious complications during
      this study. All vascular access ports remained patent. Blood oxygen level
      dependent (BOLD) activation by electrical stimulation of the median nerve using
      implanted electrodes was seen within the forelimb sensory region (S1FL) for all
      animals at all time points. The number of activated voxels decreased at time
      points 4 and 8 weeks, returning to a normal level at 12 weeks, which is
      attributed to scar tissue formation and resolution around the embedded electrode.
      The applications of this experiment extend far beyond the scope of peripheral
      nerve experimentation. These vascular access ports can be applied to any survival
      MRI study requiring repeated medication administration, intravenous contrast, or
      blood sampling.

PMID- 21726585
TI  - Evidence for suppressant effects of testosterone on sex-typical ethanol intake in
      male Sprague-Dawley rats.
AB  - Previous studies have shown that adult female rats consume more ethanol than
      adult males. Castration of male rats has been found to increase their ethanol
      intake and preference to levels significantly elevated above their sham
      gonadectomized counterparts and similar to levels observed in females. The
      purpose of the present experiment was to examine whether testosterone replacement
      in castrated adult male rats would be sufficient to restore the relatively low
      levels of ethanol drinking characteristic of intact adult male rats. Males were
      either gonadectomized and implanted with a testosterone propionate pellet (RPL),
      gonadectomized and implanted with a placebo pellet (GX), sham-gonadectomized and
      implanted with a placebo pellet (SH), or were left non-manipulated (NM).
      Voluntary ethanol intake was measured using a 2h limited-access drinking
      paradigm, with access to two bottles: one containing water, and the other a
      sweetened ethanol solution. Hormone replacement was sufficient to return ethanol
      intake and preference of castrates to levels comparable to both SH and NM control
      males. Ethanol preference of RPL males was also significantly suppressed compared
      to GX males by the end of the measurement period, whereas these group comparisons
      did not reach statistical significance for g/kg ethanol intake. These data
      suggest that testosterone serves to suppress ethanol preference in male rats, and
      may contribute to the sex differences in ethanol preference and consumption
      commonly reported in adult rats.

PMID- 21726584
TI  - Mapping vocalization-related immediate early gene expression in echolocating
      bats.
AB  - Recent studies of spontaneously vocalizing primates, cetaceans, bats and rodents
      suggest these animals possess a limited but meaningful capacity to manipulate the
      timing and acoustic structure of their vocalizations, yet the neural substrate
      for even the simplest forms of vocal modulation in mammals remains unknown.
      Echolocating bats rapidly and routinely manipulate the acoustic structure of
      their outgoing vocalizations to improve echolocation efficiency, reflecting
      cognitive rather than limbic control of the vocal motor pathways. In this study,
      we used immunohistochemical localization of immediate early gene (c-fos)
      expression to map neural activity in the brains of spontaneously echolocating
      stationary Mexican free-tailed bats. Our results support the current model of
      vocal control obtained largely through microstimulation studies, but also provide
      evidence for the contributions of two novel regions, the dorsolateral caudate
      nucleus and mediodorsal thalamic nucleus, which together suggest a
      striatothalamic feedback loop may be involved in the control of echolocation
      pulse production. Additionally, we found evidence of a motivation pathway,
      including the lateral habenula, substantia nigra pars compacta, and raphe nuclei.
      These data provide novel insights into where and how mammalian vocalizations may
      be regulated by sensory, contextual and motivational cues.

PMID- 21726586
TI  - Comparison of coherence, amplitude, and eLORETA patterns during Transcendental
      Meditation and TM-Sidhi practice.
AB  - This random-assignment study compared coherence, amplitude, and eLORETA patterns
      during practice of the Transcendental Meditation (TM) and the TM-Sidhi programs.
      The TM technique involves systematic transcending of contents of experience to a
      state of pure consciousness. The TM-Sidhi program involves sanyama-the
      simultaneous experience of dharana (fixity), dhyana (transcending) and samadhi
      (pure consciousness). Thirty-two channel EEG was recorded from experienced TM
      subjects randomly assigned to two consecutive 10-min TM sessions or to a 10-min
      TM session followed by 10-min TM-Sidhi practice. Compared to TM practice, TM
      Sidhi practice was characterized by higher frontal alpha1 and beta1 amplitudes,
      and eLORETA-identified sources of alpha1 EEG in right-hemisphere object
      recognition areas including the right parahippocampus gyrus, right fusiform
      gyrus, lingual gyrus, and inferior and medial temporal cortices. These cortical
      areas are involved in specific/holistic representation of words. The observed
      brain patterns support the descriptions of sanyama as including both specificity
      (sutras or verses), as suggested by higher frontal beta1 EEG amplitude and by
      eLORETA sources in right-hemisphere object-recognition areas, and holistic
      experience (pure consciousness) as suggested by higher frontal alpha1 EEG
      amplitude. These EEG patterns fit the complex description of sanyama.

PMID- 21726587
TI  - Physiological responses to simulated and on-road driving.
AB  - Driving simulators have become an increasingly popular tool to study and assess
      drivers. Physiological measurements not only provide an important index of an
      individual's presence in the virtual environment, but they also permit us to
      compare simulated and on-road experiences. However, at this point, few studies
      examining the ecological validity of simulated driving have included
      physiological variables. In a first study, we embedded three surprising events
      into a typical simulated road circuit. The first event consisted of a car pulling
      out suddenly from the shoulder of the road, while the remaining two events
      consisted of a green traffic light changing to amber as the driver approached the
      intersection. We noted statistically significant elevations in the mean heart
      rate (MHR) response to virtual events of about 4beats per minute (bpm) during the
      15s immediately following the events. In a second study, we directly compared
      heart rate, oxygen consumption (VO(2)), and mean ventilation (MV(E)) responses to
      similar simulated and on-road drives. The change in physiological variables from
      baseline to driving was similar between simulated and on-road conditions, and a
      very strong correlation between simulated and on-road driving values for MV(E)
      (r=0.90) was observed. MHR and maximum heart rate (HR(max)) were nonetheless
      significantly higher during on-road drives. These studies suggest that the level
      of immersion of a fixed base simulator is great enough to elicit presence, and
      achieve both relative and absolute validity for certain physiological parameters.
      Nonetheless, the absolute responses between virtual and real world experiences
      remain different. For both research and evaluation purposes, it is critical that
      we better understand the impact of the driver's perceived level of risk or
      difficulty during simulation on their driving behaviour and physiological
      responses.

PMID- 21726588
TI  - Effects of corticotropin releasing factor on spontaneous burst activity in the
      piriform-amygdala complex of in vitro brain preparations from newborn rats.
AB  - The amygdala is an important higher regulatory center of the autonomic nervous
      system, involved in respiratory and cardiovascular control, and it also plays a
      role in the formation of emotions. Corticotropin-releasing factor (CRF) is a
      neuropeptide involved in stress responses. We have examined the effects of CRF on
      the spontaneous burst activity in the piriform-amygdala complex of rat brain
      preparations in vitro. Limbic-brainstem-spinal cord preparations of 0- to 1-day
      old Wistar rats were isolated under deep ether anesthesia, and were superperfused
      in a modified Krebs solution. Bath application of 50nM CRF substantially
      increased the frequency of burst activity in the piriform-amygdala complex,
      whereas this polypeptide exerted only minor effects on C4 inspiratory activity.
      The excitatory effect of CRF on the amygdala burst was effectively blocked by the
      CRF1 antagonist, antalarmin, but not the CRF2 antagonist, astressin-2B,
      suggesting that CRF1 mediated the excitatory effect. The spatio-temporal pattern
      of the burst activity according to optical recordings was basically identical to
      the controls; the burst activity initially appeared in the piriform cortex and
      then propagated to the amygdala. The present experimental model could be useful
      for the study of role of the limbic system, including the amygdala, in stress
      responses.

PMID- 21726589
TI  - Glycine inhibits startle-mediating neurons in the caudal pontine reticular
      formation but is not involved in synaptic depression underlying short-term
      habituation of startle.
AB  - The mammalian startle response is controlled by glycine inhibition in the spinal
      cord. Evidence for additional glycine inhibition on the level of the brainstem,
      namely in the caudal pontine reticular nucleus (PnC), is controversial. Startle
      mediating PnC neurons receive fast input from sensory pathways and project to
      cranial and spinal motoneurons. Synaptic depression in the sensory synapses in
      the PnC has been indicated as underlying mechanism of short-term habituation of
      startle. We here performed patch-clamp recordings of PnC giant neurons in rat
      brain slices to test the hypothesis that the activation of glycine receptors
      inhibits PnC neurons and that this inhibition is involved in synaptic depression
      in the PnC. Glycine strongly inhibited PnC neuron activity and synaptic
      signalling, indicating that functional glycine receptors mediate a powerful
      inhibition of PnC neurons over a wide range of glycine concentrations. Strychnine
      reversed all glycine effects, but had no effect on PnC neurons itself. Thus, we
      found no evidence for a tonic glycine inhibition or for glycine activation within
      the primary startle pathway indicating that baseline startle reactions are
      unlikely to be controlled by glycine in the PnC. Most importantly, synaptic
      depression underlying short-term habituation was not affected by glycine or
      strychnine.

PMID- 21726590
TI  - Agreement between two methods of dietary data collection in female adolescent
      netball players.
AB  - The accuracy of a combined dietary data collection method (self-reported, weighed
      food diary and 24-h recall technique) in 13 female, adolescent netball players
      (14-16 years) was explored. The girls were observed for a 12 h period (08:00
      20:00), during which food and drink items were available ad libitum throughout
      the day and for the period between 20:00 and 08:00 the following morning. All
      items were covertly weighed before and after consumption to calculate observed
      energy intake. To calculate participant reported energy intake, food and drink
      items were weighed and recorded in a food diary by the participants, which was
      then supplemented with information from the 24-h recall the following morning.
      Agreement between observed and participant reported energy intake was calculated
      using the Bland and Altman technique. The mean difference between observed and
      participant reported energy intake was 0.46 MJ d(-1) (change in mean of 4.2%)
      indicating a slight bias towards over-reporting using the combined dietary data
      collection method. There was good agreement at the group level with the
      confidence interval for bias ranging from 0.00 to 0.92 MJ d(-1). The combined
      dietary data collection method is an effective technique to employ in 14-16-year
      old, female adolescent netball players when quantifying energy intake.

PMID- 21726591
TI  - Effect of rice-expressed amyloid beta in the Tg2576 Alzheimer's disease
      transgenic mouse model.
AB  - One of the main hallmarks of Alzheimer's disease (AD) is senile plaques composed
      of amyloid beta (Abeta). We developed a new edible vaccine: rice expressing GFP
      Abeta42. In a previous report, we described the production of anti-Abeta
      antibodies in B6 mice fed Abeta rice mixed with cholera toxin B subunit (CTB). In
      this report, we investigated whether Abeta rice had therapeutic effects in the
      Tg2576 AD model mice. The anti-Abeta antibody titer was increased and levels of
      intracerebral Abeta (soluble and insoluble) and serum Abeta decreased. Because
      the value of IgG1/IgG2a in the Abeta feeding group was >1, immunization via Abeta
      rice may induce a non-inflammatory Th2 reaction. We also found that the Abeta
      vaccine improved memory, as assessed in a Y-maze test. The number of arm entries
      in the Y-maze test was lower in the Abeta feeding group than in the control
      group. These results suggest that the new edible vaccine Abeta rice may have
      therapeutic effects in AD.

PMID- 21726592
TI  - The FEMA GRAS assessment of aliphatic and aromatic terpene hydrocarbons used as
      flavor ingredients.
AB  - This publication is the thirteenth in a series of safety evaluations performed by
      the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In
      1993, the Panel initiated a comprehensive program to re-evaluate the safety of
      more than 1700 GRAS flavoring substances under conditions of intended use. Since
      then, the number of flavoring substances has grown to more than 2600 substances.
      Elements that are fundamental to the safety evaluation of flavor ingredients
      include exposure, structural analogy, metabolism, pharmacokinetics and
      toxicology. Flavor ingredients are evaluated individually and in the context of
      the available scientific information on the group of structurally related
      substances. Scientific data relevant to the safety evaluation of the use of
      aliphatic and aromatic terpene hydrocarbons as flavoring ingredients are
      evaluated. The group of aliphatic and aromatic terpene hydrocarbons was
      reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as
      flavoring substances in food; their rapid absorption, metabolic detoxication, and
      excretion in humans and other animals; their low level of flavor use; the wide
      margins of safety between the conservative estimates of intake and the no
      observed-adverse effect levels determined from subchronic and chronic studies and
      the lack of significant genotoxic potential.

PMID- 21726593
TI  - Effect of vitamin E on hepatic cell proliferation and apoptosis in mice deficient
      in the p50 subunit of NF-kappaB after treatment with phenobarbital.
AB  - Phenobarbital (PB) is an efficacious and well-studied hepatic tumor promoting
      agent. Nuclear factor-kappaB (NF-kappaB) is a transcription factor activated by
      reactive oxygen and is involved in cell proliferation and apoptosis. We
      previously found that PB activates NF-kappaB and that dietary vitamin E is
      effective in decreasing PB-induced NF-kappaB DNA binding. We therefore
      hypothesized that dietary vitamin E influences PB-induced changes in cell
      proliferation and apoptosis through its action on NF-kappaB. NF-kappaB1 deficient
      mice (p50-/-) and wild-type B6129 mice were fed a purified diet containing 10 or
      250ppm vitamin E (alpha-tocopherol acetate) for 28days. At that time, half of the
      wild-type and half of the p50-/- mice were placed on the same diet with 0.05% PB
      for 10days. Compared to wild-type mice, the p50-/- mice had higher levels of cell
      proliferation and apoptosis. Cell proliferation was significantly increased by
      PB, but vitamin E did not affect hepatic cell proliferation. Apoptosis was not
      changed in mice fed PB, and there was no significant difference in apoptosis
      between control and high vitamin E treated mice. Thus, vitamin E does not appear
      to influence cell growth parameters in either wild-type or p50-/- mice.

PMID- 21726594
TI  - Benzocaine-induced methemoglobinemia in an acute-exposure rat model.
AB  - Tricaine methanesulfonate, a sedative for temporarily immobilizing fish, has a 21
      day withdrawal time. Benzocaine has been proposed as an alternative sedative
      because a withdrawal period may not be required. Since benzocaine is known to
      induce methemoglobinemia, the potential for orally administered benzocaine to
      induce methemoglobin was assessed in rats. Sprague-Dawley rats were given a
      single gavage administration of 64mg benzocaine hydrochloride per kg bw and then
      euthanized at intervals up to 120min. Plasma levels of benzocaine were relatively
      low at all times, whereas methemoglobin peaked at 24min. Additional rats were
      orally gavaged with 0-1024mg benzocaine hydrochloride per kg bw and euthanized
      after 24min. Plasma levels of benzocaine increased from 0.01MUM at 2mg per kg bw
      to 2.9MUM at 1024mg per kg bw. Methemoglobin levels did not differ from controls
      at doses up to 32mg per kg bw in females and 64mg per kg bw in males, whereupon
      the value increased to ~80% at 1024mg per kg bw. These data were used to estimate
      the potential impact of benzocaine residues in fish and suggest that the
      consumption of fish treated with benzocaine hydrochloride will not cause
      methemoglobinemia in humans.

PMID- 21726595
TI  - Effect of 2,2',4,4'-tetrahydroxybenzophenone (BP2) on steroidogenesis in
      testicular Leydig cells.
AB  - Endocrine disruptors (EDs) affect the function of animal reproductive systems.
      Recently, 2,2',4,4'-tetrahydroxybenzophenone (BP2), which is a component of UV
      protection products, was found to be an ED that interferes with the thyroid
      hormone (TH) axis. However, BP2 activity in the testis has not been well
      addressed. In this study, we have examined the effects of BP2 on steroidogenesis
      in testicular Leydig cells in connection with thyroid hormone signaling, which is
      known to play an important role in testicular development and function. Our study
      showed that BP2 affected the expression of steroidogenic enzyme genes in
      testicular Leydig cells, which is differentially regulated by thyroid
      hormone/thyroid hormone receptor (TR) signaling. In MA-10 Leydig cell line, TR/T3
      signaling increased the expression of P450c17 and P450scc, while it decreased the
      expression of StAR and 3beta-HSD. Interestingly, BP2 affected the expression of
      steroidogenic enzyme genes in a manner opposite to that of T3 signaling. BP2
      downregulated the TRalpha/T3-activation of P450c17 and P450scc expression while
      enhancing the TRalpha/T3-repression of StAR and 3beta-HSD expression. Transient
      transfection analyses with promoter-reporter constructs revealed that BP2 altered
      the expression of steroidogenic enzyme genes by affecting the cAMP and Nur77
      activated promoter activity of P450c17, StAR, and 3beta-HSD. Animal experiments
      with mice revealed that BP2 decreased the production of testosterone in the
      testis by affecting the expression of some steroidogenic enzyme genes in vivo.
      Together, these findings elucidate a molecular mechanism of BP2 action underlying
      testicular steroidogenesis and also suggest that BP2 acts, in part, as a thyroid
      antagonist that affects steroidogenesis in the testis.

PMID- 21726596
TI  - Influence of tooth-surface hydration conditions on optical coherence-tomography
      imaging.
AB  - OBJECTIVES: This study examined the influence of tooth-surface hydration
      conditions on optical coherence tomography (OCT) imaging. METHODS: Emitted light
      was coupled in a single-mode fibre-optic Michelson interferometer, and delivered
      to a sample and a reference mirror mounted on a linearly translating galvanometer
      driven by a triangular voltage waveform at a fringe-modulation frequency of 1kHz.
      Backscattered light from the sample was coupled back to the system, digitised and
      used to create two-dimensional images together with beam scanning. OCT imaging of
      the occlusal surfaces of 10 extracted human teeth was performed soon after
      mounting ('wet' condition), immediately after air blowing for 10s ('air-blow'
      condition), and at intervals thereafter ('1-min', '5-min' and '10-min'
      conditions, respectively). RESULTS: For the wet condition, three distinct peaks
      indicated the water surface, tooth surface and dentino-enamel junction.
      Backscattered light was detected at levels above noise, possibly causing grainy
      OCT images. By contrast, two distinct peaks indicating the tooth surface and
      dentino-enamel junction were observed for the air-blow and 10-min conditions,
      with greater signal intensities for the latter. The intensity was lower for the
      air-blow condition than the wet condition. The signal intensities decreased
      during storage in air at room temperature. CONCLUSION: Tooth-substrate hydration
      conditions thus appeared to influence time domain-OCT imaging.

PMID- 21726597
TI  - Effect of 3-year water storage on the performance of one-step self-etch adhesives
      applied actively on dentine.
AB  - OBJECTIVES: To evaluate the effect of the application method on the immediate and
      3-year resin-dentine bond strength (MUTBS) and nanoleakage (NL) for 3 one-step
      self-etch adhesives (Adper Prompt L-Pop; Clearfil S(3) Bond and Xeno III).
      METHODS: The occlusal enamel of 42 human molars were removed to expose a flat
      dentine surface. The adhesives were applied under inactive or active application.
      After light-curing (600mW/cm(2) for 10s), composite buildups were constructed
      incrementally and sectioned to obtain bonded sticks (0.8mm(2)) to be tested in
      tension immediately or after 3 years of water storage of water storage. For NL, 2
      bonded sticks from each tooth at each time were coated with nail varnish, placed
      in silver nitrate and polished down with SiC paper. The MUTBS data was submitted
      to a two-way repetead mesures ANOVA and Tukey's test for each adhesive
      (alpha=0.05). RESULTS: The active application showed higher immediate and 3-year
      MUTBS than the inactive application (p<0.05). An increase in the silver nitrate
      deposition was seen for all conditions after 3 years; however this was more
      pronounced for all materials under inactive application (p<0.05). CONCLUSIONS:
      The active application improves the immediate bonding performance of the adhesive
      systems. Reductions of the bond strength were observed for all materials after 3
      years, however reduced degradation rate was observed when the materials are
      applied actively in dentine.

PMID- 21726598
TI  - Cytotoxicity of 45S5 bioglass paste used for dentine hypersensitivity treatment.
AB  - OBJECTIVES: 45S5 bioglass mixed with 50% phosphoric acid has been suggested to
      treat dentine hypersensitivity and incipient enamel caries. This study is going
      to evaluate the biocompatibility of using the aforementioned technique with the
      rat pulpal cells. METHODS: The relative cytotoxicity of 45S5 bioglass on rat
      dental pulp cells was compared to the cytotoxicity of a temporary filling
      material (Caviton; GC, Japan), Type 1 glass ionomer cement (Fuji I; GC, Tokyo,
      Japan) and commercial desensitising agent (SuperSeal; Phoenix Dental, Fenton, MI,
      USA) using a transwell insert model. Cell viability was measured by means of a 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      number of viable cell counts were compared using one way ANOVA (p<0.05). The
      morphological alterations of the pulp cells were observed directly by phase
      contrast microscope. RESULTS: The results of this study indicated that cell
      viability recorded by the 45S5 bioglass paste group did not differ significantly
      from those of the Caviton, glass ionomer or superseal, moreover pulpal cells
      microscopic analysis revealed that 45S5 bioglass elicited minimal toxic effect.
      CONCLUSIONS: 45S5 bioglass paste can serve as a biocompatible material that can
      potentially be used safely on dentine.

PMID- 21726599
TI  - Electrophysiological correlates of emotional processing in sensation seeking.
AB  - Previous studies have consistently reported a relationship between sensation
      seeking and emotional reactivity. However, little is known about the neural
      correlates and the time course of emotional processing in sensation seeking. The
      present study addressed these issues by recording event-related potentials (ERPs)
      during an emotional oddball task. Valence effect was significant at N2, P3 and
      LPP whereas arousal effect was significant at P3 and LPP. More importantly, low
      sensation seekers (LSSs) exhibited an increased emotional N2 whereas high
      sensation seekers (HSSs) showed an enhanced emotional P3. Furthermore, the
      arousal effect was similar across the two groups, but the valence effect at N2
      stage was significant in LSSs instead of HSSs. These findings suggest that LSSs
      tend to show a more active general alerting system toward emotional stimuli,
      particularly for negative stimuli, whereas HSSs tend to display a stronger
      preference for intense stimulation irrespective of the emotional valence.

PMID- 21726600
TI  - Vitamin D metabolism and biological activities.

PMID- 21726601
TI  - Lactoferrin a multiple bioactive protein: an overview.
AB  - BACKGROUND: Lactoferrin (Lf) is an 80kDa iron-binding glycoprotein of the
      transferrin family. It is abundant in milk and in most biological fluids and is a
      cell-secreted molecule that bridges innate and adaptive immune function in
      mammals. Its protective effects range from anticancer, anti-inflammatory and
      immune modulator activities to antimicrobial activities against a large number of
      microorganisms. This wide range of activities is made possible by mechanisms of
      action involving not only the capacity of Lf to bind iron but also interactions
      of Lf with molecular and cellular components of both hosts and pathogens. SCOPE
      OF REVIEW: This review summarizes the activities of Lf, its regulation and
      potential applications. MAJOR CONCLUSIONS: The extensive uses of Lf in the
      treatment of various infectious diseases in animals and humans has been the
      driving force in Lf research however, a lot of work is required to obtain a
      better understanding of its activity. GENERAL SIGNIFICANCE: The large potential
      applications of Lf have led scientists to develop this nutraceutical protein for
      use in feed, food and pharmaceutical applications. This article is part of a
      Special Issue entitled Molecular Mechanisms of Iron Transport and Disorders.

PMID- 21726603
TI  - Inhibition of mitochondrial Na+-dependent Ca2+ efflux by 17beta-estradiol in the
      rat hippocampus.
AB  - Our results, as well as those of others, have indicated that 17beta-estradiol
      (E2) exerts its nongenomic effects in neuronal cells by affecting plasma membrane
      Ca(2+) flux. In neuronal cells mitochondria possess Ca(2+) buffering properties
      as they both sequester and release Ca(2+). The goal of this study was to examine
      the rapid non-genomic effect of E2 on mitochondrial Ca(2+) transport in
      hippocampal synaptosomes from ovariectomised rats. In addition, we aimed to
      determine if, and to what extent, E2 receptors participated in mitochondrial
      Ca(2+) transport modulation by E2 in vitro. E2-specific binding and Ca(2+)
      transport was monitored. At physiological E2 concentrations (0.1-1.5 nmol/L),
      specific E2 binding to mitochondria isolated from hippocampal synaptosomes was
      detected with a B(max.) and K(m) of 37.6+/-2.6 fmol/mg protein and 0.69+/-0.14
      nmol/L of free E2, respectively. The main mitochondrial Ca(2+) influx mechanism
      is the Ruthenium Red-sensitive uniporter driven by mitochondrial membrane
      potential. Despite no effect of E2 on Ca(2+) influx, a physiological E2
      concentration (0.5 nmol/L) protected mitochondrial membrane potential and
      consequently Ca(2+) influx from the uncoupling agent carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone (1 MUmol/L). In neuronal cells the predominant
      mitochondrial Ca(2+) efflux mechanism is the Na(+)/Ca(2+) exchanger. E2 caused
      Ca(2+) efflux inhibition (by 46%) coupled with increased affinity of the
      Na(+)/Ca(2+) exchanger for Na(+). Using E2 receptor (ERalpha and ERbeta)
      antagonists and agonists, we confirmed ERbeta's involvement in E2-induced
      mitochondrial membrane potential protection as well as Ca(2+) efflux inhibition.
      In summary, our results indicate that the non-genomic neuromodulatory role of E2
      in rat hippocampus is achieved by affecting mitochondrial Ca(2+) transport via,
      in part, mitochondrial ERbeta.

PMID- 21726602
TI  - Transferrin as a model system for method development to study structure, dynamics
      and interactions of metalloproteins using mass spectrometry.
AB  - BACKGROUND: Transferrin (Tf) is a paradigmatic metalloprotein, which has been
      extensively studied in the past and still is a focal point of numerous
      investigation efforts owing to its unique role in iron homeostasis and enormous
      promise as a component of a wide range of therapies. SCOPE OF REVIEW:
      Electrospray ionization mass spectrometry (ESI MS) is a potent analytical tool
      that has been used successfully to study various properties of Tf and Tf-based
      products, ranging from covalent structure and metal binding to conformation and
      interaction with their physiological partners. MAJOR CONCLUSIONS: Various ESI MS
      based techniques produce unique information on Tf properties and behavior that is
      highly complementary to information provided by other experimental techniques.
      GENERAL SIGNIFICANCE: The experimental ESI MS-based techniques developed for Tf
      studies are not only useful for understanding of fundamental aspects of the iron
      binding properties of this protein and optimizing Tf-based therapeutic products,
      but can also be applied to study a range of other metalloproteins. This article
      is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron
      transport and disorders.

PMID- 21726604
TI  - Expression, distribution and glutamate uptake activity of high affinity
      excitatory aminoacid transporters in in vitro cultures of embryonic rat dorsal
      root ganglia.
AB  - Glutamate is the major mediator of excitatory signalling in the mammalian central
      nervous system, but it has recently been shown to play a role in the transduction
      of sensory input at the periphery and in peripheral neuropathies. New advances in
      research have demonstrated that rat peripheral sensory terminals and dorsal root
      ganglia (DRG) express molecules involved in glutamate signalling, including high
      affinity membrane-bound glutamate transporters (GLAST [glutamate aspartate
      transporter], GLT1 [glutamate transporter 1], EAAC1 [excitatory aminoacid
      transporter 1]) and that alterations in their expression and/or functionality can
      be implicated in several models of peripheral neuropathy, neuropathic pain and
      hyperalgesia. Here we describe, through immunoblotting, immunofluorescence assays
      and beta-counter analysis of [(3)H] l-glutamate uptake, the expression,
      distribution and activity of the glutamate transporters in in vitro cultures of
      embryonic dorsal root ganglia sensory neurons, sensory neurons+satellite cells
      and satellite cells. In this work we demonstrated that glutamate transporters are
      expressed in all cultures with a peculiar pattern of distribution. Even if GLAST
      is strongly detected in satellite cells, it is slightly expressed also in sensory
      neurons. GLT1 immunostaining is very weak in DRG neurons, but it was evident in
      the satellite cells. Finally, EAAC1 is localized in the soma and in the neuritis
      of sensory neurons, while it is not detectable in satellite cells. Moreover, all
      the cell cultures showed a strong sodium-energy-dependent glutamate uptake
      activity and it is more marked in neurons alone or in co-culture with satellite
      cells compared to satellite cells alone. Finally, we show that the complete or
      partial pharmacological inhibition of glutamate transporters virtually completely
      or partially abolish glutamate uptake in all cell culture. These results, that
      demonstrate that functionally active glutamate transporters can be studied in
      dorsal root ganglia cell cultures, provide further evidence for a role of
      glutamatergic transport in the peripheral nervous system and will be useful for
      testing whether any changes occur in in vitro models of peripheral nervous system
      damage.

PMID- 21726605
TI  - Effects of conditioning history on selective stimulus control by elements of
      compound discriminative stimuli.
AB  - Effects of prior discrimination training on stimulus control by color and shape
      dimensions of compound stimuli were studied with college students. In Phase 1,
      single-stimulus discrimination training was conducted for two values of color and
      shape. Phase 2 discrimination training employed two 2-dimensional compound
      stimuli composed of the color and shape stimuli trained in Phase 1. For conflict
      compound stimuli, the stimulus-response-consequence contingency was altered
      between phases for one stimulus dimension (target dimension), but not for the
      other, non-target, dimension. Level of congruence (100%, 25%, and 0%) of the
      contingency for the target dimension between phases was manipulated across
      groups. When each stimulus value was tested in Phase 3, level of Phase-2
      consistent responding to the target dimension varied with level of Phase-1-to
      Phase-2 congruence. In Experiment 2, training history for the non-target
      dimension was altered across three conditions: (a) Correlated with reinforcement,
      as in Experiment 1, (b) No-Training, or (c) Not-Correlated. Phase-2-consistent
      responding to the target cue in Phase 3 was lower under the latter conditions
      than under the Correlated condition, indicating that the non-target dimension
      modulated control by the target dimension, consistent with stimulus competition.
      The data suggest elemental, rather than configural processing of the compound
      stimuli during Phase 2.

PMID- 21726606
TI  - Behavioral responses to physical vs. social novelty in male and female laboratory
      rats.
AB  - Most behavioral tests used with laboratory rodents involve measuring behavioral
      responses to physical novelty. However, laboratory rodents are often derived from
      highly social species for which novel social stimuli may induce different levels
      of fear or curiosity compared to novel physical objects. We hypothesized that
      behavioral responses will differ in response to novel physical vs. social cues,
      and that females may show more exploration of social novelty, based on prior
      studies indicating that females more actively seek social support during duress
      compared to males. We compared young (55-day-old) Sprague-Dawley rats' responses
      to an arena filled with novel objects ("physical") or a novel same-sex caged
      conspecific ("social"). Rats were more active and spent twice as much time in
      contact with the novel social stimulus compared to novel physical stimuli.
      Although females were more active than males, females were not particularly more
      exploratory in the social arena compared to males. The results indicate that a
      novel social partner (even a caged one with limited ability to interact) elicits
      more exploration than novel objects for both male and female rats.

PMID- 21726607
TI  - TGF-beta1 inhibits the growth and metastasis of tongue squamous carcinoma cells
      through Smad4.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that
      regulates cell growth, differentiation, migration, apoptosis and extracellular
      matrix remodeling. TGF-beta1 transduces signals from the cell membrane to the
      cell nucleus through serine/threonine kinase receptors and their downstream
      effectors, Smad molecules. Although many studies have been focused on TGF-beta1
      Smad signaling pathway, the role of TGF-beta1/Smad in tongue squamous cell
      carcinoma is not fully understood. In the present study, we used a series of cell
      function assays to examine the role of TGF-beta-Smad4 signaling in tongue
      squamous cell carcinoma. We observed the effects of TGF-beta1 on the growth and
      metastatic potential of the tongue squamous cell carcinoma cell line Ts, which
      expresses lower level of Smad4 protein. We found that Smad4 could decrease TGF
      beta1-induced cell proliferation, and that Smad4 overexpression promoted Ts cell
      apoptosis. In Ts vector control cells, TGF-beta1 increased the expression of
      TbetaRII, as well as MMP-2, and enhanced cell invasion through the basement
      membrane, and then induced cell metastasis. However in Ts cells stably expressing
      Smad4, Smad4 mediated TGF-beta1-induced p21 expression promoted cell apoptosis
      and inhibited cell proliferation, delayed MMP-2 expression, and decreased cell
      metastasis. Therefore, TGF-beta1 plays distinct roles in the Smad4-dependent and 
      independent signaling pathways.

PMID- 21726608
TI  - HI 6 human serum albumin nanoparticles--development and transport over an in
      vitro blood-brain barrier model.
AB  - The standard treatment of intoxication with organophosphorus (OP) compounds
      includes the administration of oximes acting as acetylcholinesterase (AChE)
      reactivating antidotes. However, the blood-brain barrier (BBB) restricts the
      rapid transport of these drugs from the blood into the brain in therapeutically
      relevant concentrations. Since human serum albumin (HSA) nanoparticles enable the
      delivery of a variety of drugs across the BBB into the brain, HI 6
      dimethanesulfonate and HI 6 dichloride monohydrate were bound to these
      nanoparticles in the present study. The resulting sorption isotherms showed a
      better fit to Freundlich's empirical adsorption isotherm than to Langmuir's
      adsorption isotherm. At the pH of 8.3 maximum drug binding capacities of 344.8
      MUg and 322.6 MUg per mg of nanoparticles were calculated for HI 6
      dimethanesulfonate and HI 6 dichloride monohydrate, respectively. These
      calculated values are higher than the adsorption capacity of 93.5 MUg/mg for
      obidoxime onto HSA nanoparticles determined in a previous study. In vitro testing
      of the nanoparticulate oxime formulations in primary porcine brain capillary
      endothelial cells (pBCEC) demonstrated an up to two times higher reactivation of
      OP-inhibited AChE than the free oximes. These findings show that nanoparticles
      made of HSA may enable a sufficient antidote OP-poisoning therapy with HI 6
      derivatives even within the central nervous system (CNS).

PMID- 21726609
TI  - The role of miR-506 in transformed 16HBE cells induced by anti-benzo[a]pyrene
      trans-7,8-dihydrodiol-9,10-epoxide.
AB  - Growing evidence indicates that the alteration of microRNA (miRNA) expression in
      tumors that is induced by chemical carcinogens plays an important role in tumor
      development and progression. However, the mechanism underlying miRNA involvement
      in lung carcinogenesis induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10
      epoxide (anti-BPDE) remains unclear. In our study, we used the malignant
      transformation of human bronchial epithelial cells (16HBE-T) induced by anti-BPDE
      to explore the mechanisms of human lung carcinogenesis. We found that expression
      of miR-506 was reduced in 16HBE-T transformed malignant human bronchial
      epithelial cells compared with 16HBE normal human bronchial epithelial cells.
      Restoration of miR-506 in 16HBE-T cells led to a decrease in cell proliferation,
      G0/G1 phase cell cycle arrest, as well as significantly suppressed anchorage
      dependent growth in vitro and tumor growth inhibition in a nude mouse xenograft
      model. In addition, we provided novel evidence regarding the role miR-506
      potentially plays in negatively regulating the protein and mRNA expression level
      of N-Ras in cancer cells. Together, these findings revealed that miR-506 acts as
      an anti-oncogenic miRNA (anti-oncomir) in malignantly transformed cells. The
      identification of tumor suppressive miRNAs could provide new insight into the
      molecular mechanisms of chemical carcinogenesis.

PMID- 21726610
TI  - Toluene exposure during brain growth spurt and adolescence produces differential
      effects on N-methyl-D-aspartate receptor-mediated currents in rat hippocampus.
AB  - Toluene, an industrial organic solvent, is voluntarily inhaled as drug of abuse.
      Because inhibition of N-methyl-d-aspartate (NMDA) receptors is one of the
      possible mechanisms underlying developmental neurotoxicity of toluene, the
      purpose of the present study was to examine the effects of toluene exposure
      during two major neurodevelopmental stages, brain growth spurt and adolescence,
      on NMDA receptor-mediated current. Rats were administered with toluene (500
      mg/kg, i.p.) or corn oil daily over postnatal days (PN) 4-9 (brain growth spurt)
      or PN 21-26 (early adolescence). Intracellular electrophysiological recordings
      employing in CA1 pyramidal neurons in the hippocampal slices were performed
      during PN 30-38. Toluene exposure during brain growth spurt enhanced NMDA
      receptor-mediated excitatory postsynaptic currents (EPSCs) by electrical
      stimulation, but impaired the paired-pulse facilitation and NMDA response by
      exogenous application of NMDA. Toluene exposure during adolescence resulted in an
      increase in NMDA receptor-mediated EPSCs and a decrease in exogenous NMDA-induced
      currents, while lack of any effect on paired-pulse facilitation. These findings
      suggest that toluene exposure during brain growth spurt and adolescence might
      result in an increase in synaptic NMDA receptor responsiveness and a decrease in
      extrasynaptic NMDA receptor responsiveness, while only toluene exposure during
      brain growth spurt can produce presynaptic modulation in CA1 pyramidal neurons.
      The functional changes in NMDA receptor-mediated transmission underlying
      developmental toluene exposure may lead to the neurobehavioral disturbances.

PMID- 21726611
TI  - Up-regulation of cyclin D1 by JNK1/c-Jun is involved in tumorigenesis of human
      embryo lung fibroblast cells induced by a low concentration of arsenite.
AB  - Inorganic arsenic, a ubiquitous environmental contaminant, is associated with an
      increased risk of cancer. There are several hypotheses regarding arsenic-induced
      carcinogenesis. The mechanism of action remains obscure, although hyper
      proliferation of cells is involved. In the present study, the molecular
      mechanisms underlying the proliferation and malignant transformation of human
      embryo lung fibroblast (HELF) cells induced by a low concentration of arsenite
      were investigated. The results reveal that a low concentration of arsenite
      induces cell proliferation and promotes cell cycle transition from the G(1) to
      the S phase. Moreover, arsenite activates the JNK1/c-Jun signal pathway, but not
      JNK2, which up-regulates the expression of cyclin D1/CDK4 and phosphorylates the
      retinoblastoma (Rb) protein. Blocking of the JNK1/c-Jun signal pathway suppresses
      the increases of cyclin D1 expression and Rb phosphorylation, which attenuates
      cell proliferation, reduces the transition from the G1 to the S phase, and
      thereby inhibits the neoplastic transformation of HELF cells induced by a low
      concentration of arsenite. Thus, activation of the JNK1/c-Jun pathway up
      regulates the expression of cyclin D1, which is involved in the tumorigenesis
      caused by a low concentration of arsenite.

PMID- 21726612
TI  - Differential effects of female sex hormones on cellular recruitment and tracheal
      reactivity after formaldehyde exposure.
AB  - Female sex hormones (FSHs) exert profound regulatory effects on the course of
      lung inflammation due to allergic and non-allergic immune responses. As pollution
      is one of the pivotal factors to induce lung dysfunction, in this study we
      investigated the modulatory role of FSHs on lung inflammation after a
      formaldehyde (FA) exposure. For this purpose, lung and systemic inflammatory
      responses were evaluated in terms of leukocytes countings in bronchoalveolar
      lavage (BAL), peripheral blood and bone marrow lavage from 7-day ovariectomized
      (OVx) and Sham-OVx rats subjected to FA inhalation for 3 consecutive days. The
      hypothesized link between effects of FSHs on expression of adhesion molecules and
      mast cells degranulation was also studied. Once exposed to FA, Sham-OVx rats
      increased the number of total cells recovered in BAL and of leukocytes in
      peripheral blood, and decreased the counts in bone marrow. By contrast, in OVx
      rats upon FA exposure there was a reduction of the total cells counts in BAL and
      of blood leukocytes; lung expressions of ICAM-1 and Mac-1 were depressed, but the
      number of bone marrow cells did not vary. Estradiol treatment of OVx rats
      increased the total cells in BAL and decreased the number of blood leukocytes,
      whereas the number of bone marrow cell remained unaltered. Progesterone
      treatment, in turn increased the total cells in BAL and blood leukocytes, but
      decreased the number of bone marrow cells. OVx rats exposed to FA developed
      tracheal hyperresponsiveness to methacholine (MCh). A similarly altered response
      was found between the tracheal segments of Sham-OVx rats after FA exposure and
      that found in tracheae of naive rats. Estradiol treatment prevented FA-induced
      tracheal hyperresponsiveness to MCh whereas progesterone was ineffective in this
      regard. In addition, OVx rats upon FA exposure significantly increased both, the
      ability of mast cell degranulation and serum corticosterone levels. In
      conclusion, it was found that FSHs act by distinct control mechanisms on FA
      induced lung inflammation and tracheal hyperresponsiveness, since at low
      circulating levels of FSHs (such as those after OVx) there is some resistance to
      the development of a lung inflammatory response, but the cholinergic tracheal
      responsiveness is exacerbated. Our data also help to understand the involvement
      of FSHs on mast cells activity after pollutants exposure and add information
      regarding the role of FSHs on the mechanisms related to endothelium-leukocyte
      interactions.

PMID- 21726613
TI  - Reference material development for calibration and verification of image-based
      particle analyzers.
AB  - The need is well recognized for suitable reference populations for calibrating
      and verifying the size and concentration accuracy of particle analysis
      instruments for use in the measurement of suspended protein particles in
      biopharmaceuticals. Polystyrene bead standards are normally used as a reference
      material for calibrating and validating particle analyzers. However, these
      standards, unlike protein particles, are easily detected and do not challenge the
      sensitivity of optical instruments. Groups of instruments verified only with
      beads can still exhibit significant differences in measuring concentrations of
      more challenging protein particles. To minimize these and obtain consistent
      concentration measurements between instruments, reference populations must
      closely resemble protein aggregates in possessing high transparency and a
      refractive index close to typical protein matrix fluids. This paper describes
      work on evaluating a promising reference candidate and the use of this to
      harmonize the performance of Micro-Flow Imaging instruments. Results show that
      use of a suitable reference population can significantly increase measurement
      consistency when multiple instruments are used to characterize the same protein
      particle suspension.

PMID- 21726614
TI  - A priori performance predictions in the pharmaceutical sciences.

PMID- 21726615
TI  - Antibacterial electrospun poly(E-caprolactone)/ascorbyl palmitate nanofibrous
      materials.
AB  - The one-step incorporation of ascorbyl palmitate (AP), a widely used derivative
      of vitamin C, into nanofibrous mats of poly(E-caprolactone) (PCL) by
      electrospinning was demonstrated. The incorporation of AP was attested by IR
      spectroscopy; the AP content was determined by thermogravimetric analysis (TGA);
      and the surface composition of the mats: by X-ray photoelectron spectroscopy
      (XPS). The possibility for deposition of silver nanoparticles onto PCL/AP mats
      using the ability of AP to reduce silver ions was demonstrated. The silver
      content was determined by TGA, and the silver nanoparticles were observed by
      transmission electron microscopy (TEM). The nanoparticles were composed of
      elemental silver, as verified by XPS analyses. The UV-vis spectrophotometric
      analyses, study on quenching of the free 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      radicals and microbiological tests against the pathogenic microorganism
      Staphylococcus aureus showed that AP preserved its stability and its antioxidant
      and antibacterial activity when incorporated in the nanofibrous mats.

PMID- 21726616
TI  - Development of mini-tablets with 1mm and 2mm diameter.
AB  - The feasibility of formulating mini-tablets with 1mm diameter on a rotary-die
      press in comparison to mini-tablets of 2mm was investigated. To gain insight into
      the production of 1mm mini-tablets, three model drugs of different compression
      characteristics were chosen, namely quinine hydrochloride, ibuprofen and spray
      dried gentian extract. A high drug load in combination with robust and
      reproducible mechanical properties was requested. Depending on the individual
      drug substance, mini-tablets were produced by direct compression or after roll
      compaction/dry granulation. The tensile strength, mass, and their variation
      coefficients were determined to assess the mechanical properties of the tablets.
      The content uniformity and the dissolution behavior of selected batches were
      analyzed. For the first time 1mm mini-tablets could be successfully produced by
      direct compression (90% quinine hydrochloride; 90% dried gentian extract) and
      after roll compaction (70% ibuprofen). Depending on the applied compression
      pressure, 1mm mini-tablets with quinine hydrochloride exhibited robust mechanical
      properties (e.g. median tensile strength of 2.02N/mm(2)) with equal or lower
      variance of distribution compared to the 2mm compacts. With respect to content
      uniformity of dosage forms, 1mm mini-tablets containing 80% quinine hydrochloride
      met the requirements of the European Pharmacopeia (AV=6.8).

PMID- 21726617
TI  - In vivo imaging of DNA lipid nanocapsules after systemic administration in a
      melanoma mouse model.
AB  - The biodistribution of intravenously injected DNA lipid nanocapsules (DNA LNCs),
      encapsulating pHSV-tk, was analysed by in vivo imaging on an orthotopic melanoma
      mouse model and by a subsequent treatment with ganciclovir (GCV), using the gene
      directed enzyme prodrug therapy (GDEPT) approach. Luminescent melanoma cells,
      implanted subcutaneously in the right flank of the mice, allowed us to follow
      tumour growth and tumour localisation with in vivo bioluminescence imaging (BLI).
      In parallel, DNA LNCs or PEG DNA LNCs (DNA LNCs recovered with PEG(2000))
      encapsulating a fluorescent probe, DiD, allowed us to follow their
      biodistribution with in vivo biofluorescence imaging (BFI). The BF-images
      confirmed a prolonged circulation-time for PEG DNA LNCs as was previously
      observed on an ectotopic model of glioma; comparison with BL-images evidenced the
      colocalisation of PEG DNA LNCs and melanoma cells. After these promising results,
      treatment with PEG DNA LNCs and GCV on a few animals was performed and the
      treatment efficacy measured by BLI. The first results showed tumour growth
      reduction tendency and, once optimised, this therapy strategy could become a new
      option for melanoma treatment.

PMID- 21726618
TI  - Improved intestinal delivery of salmon calcitonin by water-in-oil microemulsions.
AB  - Therapeutic peptides are highly potent and specific in their functions, but
      difficulties in their oral administration require parallel development of viable
      delivery systems to improve their oral bioavailability. The objective of this
      study was to explore the feasibility of water-in-oil (w/o) microemulsions for
      improving the absorption of intraduodenally administered salmon calcitonin (sCT).
      The w/o microemulsions were prepared from medium chain triglyceride, Tween 80 and
      Span 80 or soybean phosphatidylcholine, propylene glycol and phosphate saline,
      and characterized by particle size and in vitro physical stability under dilution
      with different physiologically relevant diluents. The effects of addition of
      polymers such as hydroxypropylmethylcellulose and Carbomer into aqueous phase on
      the properties of microemulsions were assessed. sCT was efficiently encapsulated
      into microemulsions with nanoscaled diameter ranged from about 6 to 134nm. As
      expected from the non-ionic nature of the investigated microemulsions, the
      physical stability, evaluated by visual inspection, the particle size and leakage
      percent under dilution, was found to be unaffected by pH and/or ionic strength of
      diluents and it was opposite for the microemulsions with ionic components. In
      addition, the dilution extent had a pronounced effect on the physical stability
      of the diluted microemulsions. The effect of polymers added into aqueous phase of
      the microemulsions on the absorption of the drug entrapped in microemulsions with
      different components was investigated. The optimized microemulsions were shown to
      generate substantial enhancement (up to 4-fold) of relative pharmacological
      activity of sCT with regard to the control solution of the drug. This indicated
      that the w/o microemulsions could offer the potential to significantly improve
      intestinal absorption of sCT.

PMID- 21726619
TI  - Development of a mucoadhesive nanoparticulate drug delivery system for a targeted
      drug release in the bladder.
AB  - PURPOSE: Purpose of the present study was the development of a mucoadhesive
      nanoparticulate drug delivery system for local use in intravesical therapy of
      interstitial cystitis, since only a small fraction of drug actually reaches the
      affected site by conventional treatment of bladder diseases via systemic
      administration. METHODS: Chitosan-thioglycolic acid (chitosan-TGA) nanoparticles
      (NP) and unmodified chitosan NP were formed via ionic gelation with
      tripolyphosphate (TPP). Trimethoprim (TMP) was incorporated during the
      preparation process of NP. Thereafter, the mucoadhesive properties of NP were
      determined in porcine urinary bladders and the release of TMP among simulated
      conditions with artificial urine was evaluated. RESULTS: The particles size
      ranged from 183nm to 266nm with a positive zeta potential of +7 to +13mV. Under
      optimized conditions the encapsulation efficiency of TMP was 37%. The adhesion of
      prehydrated chitosan-TGA NP on the urinary bladder mucosa under continuous urine
      voiding was 14-fold higher in comparison to unmodified chitosan NP. Release
      studies indicated a more sustained TMP release from covalently cross linked
      particles in comparison to unmodified chitosan-TPP NP over a period of 3h in
      artificial urine at 37 degrees C. CONCLUSION: Utilizing the method described
      here, chitosan-TGA NP might be a useful tool for local intravesical drug delivery
      in the urinary bladder.

PMID- 21726620
TI  - Effect of storage on microstructural changes of Carbopol polymers tracked by the
      combination of positron annihilation lifetime spectroscopy and FT-IR
      spectroscopy.
AB  - Different types of Carbopols are frequently applied excipients of various dosage
      forms. Depending on the supramolecular structure, their water sorption behaviour
      could significantly differ. The purpose of the present study was to track the
      supramolecular changes of two types of Carbopol polymers (Carbopol 71G and Ultrez
      10NF) alone and in their physical mixture with a water-soluble drug, vitamin
      B(12), as a function of storage time. The combination of FT-IR spectroscopy,
      positron annihilation lifetime spectroscopy (PALS) and Doppler-broadening
      spectroscopy was applied to follow the effect of water uptake on the structural
      changes. Our results indicate that water-induced interactions between polymeric
      chains can be sensitively detected. This enables the prediction of stability of
      dosage forms in the course of storage.

PMID- 21726621
TI  - Age-dependent vasorelaxation of Casimiroa edulis and Casimiroa pubescens extracts
      in rat caudal artery in vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leaf and seed decoctions of Casimiroa spp. are
      used in Mexican traditional medicine to treat high blood pressure. Previous
      researches showed as Casimiroa extracts are able to induce relaxation of rat
      aortic and caudal arteries. To study the influence of the aging, we determined
      the vascular effect induced by extracts of Casimiroa edulis and Casimiroa
      pubescens in arterial tissues from young and old rats. MATERIALS AND METHODS: The
      activity of Casimiroa edulis extracts: hexanic-leaf (Ce5), methanolic-leaf (Ce6),
      hexanic-seed (Ce7) and methanolic-seed (Ce8), and Casimiroa pubescens: hexanic
      leaf (Cp9), methanolic-leaf (Cp10), hexanic-seed (Cp11) and methanolic-seed
      (Cp12) were investigated in precontracted caudal arteries of young (4 months) and
      old (20 months) rats. RESULTS: The Casimiroa extracts tested at 20 MUg/ml induced
      vasorelaxation in phenylephrine-precontracted arterial tissues both in young and
      old arterial tissues. Methanolic seed extracts of Casimiroa edulis (Ce8) and
      Casimiroa pubescens (Cp12) caused a higher relaxation in young than in old
      arterial tissues. Nifedipine (0.01 MUM) did not change the vasorelaxation induced
      by Casimiroa edulis extract either in young and old rat arterial tissues.
      CONCLUSIONS: The vasorelaxation induced by Casimiroa edulis and Casimiroa
      pubescens extracts is decreased from aging since the effects were higher in young
      than in old rat arterial tissues. However, the methanolic-seed extracts of both
      plant species induced a relevant vasorelaxation also in old arterial tissues.
      Thus the results support the traditional use of Casimiroa decoctions as
      antihypertensive, also in elderly.

PMID- 21726622
TI  - Icaritin induces cell death in activated hepatic stellate cells through
      mitochondrial activated apoptosis and ameliorates the development of liver
      fibrosis in rats.
AB  - AIM OF THE STUDY: Icaritin is an active ingredient extracted from the plant Herba
      Epimedium Sagittatum (Sieb. et Zucc.) Maxim. The purpose of this study is to
      investigate the effects and mechanisms of icaritin-induced cell death in
      activated hepatic stellate cells (HSCs) and ameliorating the development of liver
      fibrosis in rats. MATERIALS AND METHODS: : In vitro, icaritin-induced cell death
      rates in HSC-T6 (rat) and LX-2 (human) HSC lines as well as normal hepatocyte
      cell lines HL-7702 (L02) and WRL-68 were assayed by MTT method, and the apoptotic
      ratios were detected by both flow cytometry and the Annexin-V-FITC Apoptosis
      Detection Kit. A Whole Rat Genome Microarray Kit was used to identify expression
      of interest genes through fold-change screening. In vivo study, experimental
      liver fibrosis models were built by carbon tetrachloride (CCl(4)) or common bile
      duct ligation (CBDL) in Wistar rats. Icaritin (1mg/kg/day, three days a week) was
      administered by gastric gavage for four weeks (n=6 per group). At the end of the
      study, serum levels of aspartate aminotransferase (AST), alanine aminotransferase
      (ALT) as well as the contents of hydroxyproline and collagen I in liver tissues
      were measured. Histopathological changes and the distribution of activated HSCs
      were observed in the liver tissues using hematoxyline-eosin (HE) staining and
      immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA). RESULTS:
      Icaritin induced apoptosis in HSC-T6 and LX-2 in a concentration- and time
      dependent manner with little toxicity to normal hepatocyte cell lines. The IC(50)
      of icaritin in HSC-T6 was 12.83 MUM at 48 h. Apoptotic ratio of HSC-T6 treated
      with 24 MUM icaritin was 20.19%, and the G2 phase of the cell cycle did not occur
      (P<0.05). Gene analysis showed that icaritin up-regulated Bak-1, Bmf and Bax
      expression while significantly down-regulated Bcl-2 expression (vs. control
      group, P<0.01). These results suggested that mitochondrial pathway played an
      important role in icaritin-induced apoptosis in activated HSCs. In vivo results
      showed that icaritin reduced the number of activated HSCs, and brought the
      elevated levels of AST, ALT, hydroxyproline and collagen I to normal or near
      normal values (vs. model group, P<0.05). CONCLUSIONS: Icaritin can induce cell
      death in activated HSCs through mitochondria-mediated apoptosis, ameliorate the
      progression of hepatic fibrosis in rats, and could be a promising drug for
      treating liver fibrosis.

PMID- 21726623
TI  - Downstream processing of stevioside and its potential applications.
AB  - Stevioside is a natural sweetener extracted from leaves of Stevia rebaudiana
      Bertoni, which is commercially produced by conventional (chemical/physical)
      processes. This article gives an overview of the stevioside structure, various
      analysis technique, new technologies required and the advances achieved in recent
      years. An enzymatic process is established, by which the maximum efficacy and
      benefit of the process can be achieved. The efficiency of the enzymatic process
      is quite comparable to that of other physical and chemical methods. Finally, we
      believe that in the future, the enzyme-based extraction will ensure more cost
      effective availability of stevioside, thus assisting in the development of more
      food-based applications.

PMID- 21726624
TI  - Stem cell cultivation in bioreactors.
AB  - Cell-based therapies have generated great interest in the scientific and medical
      communities, and stem cells in particular are very appealing for regenerative
      medicine, drug screening and other biomedical applications. These unspecialized
      cells have unlimited self-renewal capacity and the remarkable ability to produce
      mature cells with specialized functions, such as blood cells, nerve cells or
      cardiac muscle. However, the actual number of cells that can be obtained from
      available donors is very low. One possible solution for the generation of
      relevant numbers of cells for several applications is to scale-up the culture of
      these cells in vitro. This review describes recent developments in the
      cultivation of stem cells in bioreactors, particularly considerations regarding
      critical culture parameters, possible bioreactor configurations, and integration
      of novel technologies in the bioprocess development stage. We expect that this
      review will provide updated and detailed information focusing on the systematic
      production of stem cell products in compliance with regulatory guidelines, while
      using robust and cost-effective approaches.

PMID- 21726625
TI  - Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in
      myelination of the rodent brain: lessons from PACAP-deficient mice.
AB  - Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of
      its effect on the elevation of intracellular cAMP level, strongly influences
      brain development including myelination. While proliferation of oligodendroglial
      progenitors is stimulated by PACAP applied in vitro, their differentiation is
      inhibited. However, the in vivo role of PACAP on myelination has never been
      examined. In the present study the role of endogenous PACAP in myelination was
      examined in PACAP-deficient mice, in several areas of the brain with a special
      attention to the cerebral cortex. In young postnatal and adult mice myelination
      was studied with immunohistochemistry detecting a protein present in the myelin
      sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron
      microscopy. Results obtained in PACAP-deficient mice were compared to age-matched
      wild type controls. We found that the sequence of myelination in the PACAP
      deficient animals was similar to that observed in controls. According to this, in
      both PACAP-deficient and wild type mice, the somatosensory cortex was myelinated
      before motor areas that preceded the myelination of associational cortical areas.
      Archicortical associational areas such as the cingulate cortex were myelinated
      before neocortical areas. Myelination in the corpus callosum followed the known
      rostro-caudal direction in both PACAP-deficient and wild type animals, and the
      ventrolateral part of the corpus callosum was myelinated earlier than the
      dorsomedial part in both groups. In contrast to the similarity in its sequence,
      striking difference was found in the onset of myelination that started earlier in
      PACAP-deficient mice than in wild type controls in all of the examined brain
      regions, including cerebral archi- and neocortex. The first myelinated axons in
      each of the examined brain regions were observed earlier in the PACAP-deficient
      mice than in controls. When age-matched animals of the two groups were compared,
      density of myelinated fibers in the PACAP-deficient mice was higher than in
      controls in all of the examined areas. We propose that endogenous PACAP exerts an
      inhibitory role on myelination in vivo. Since myelin sheath of the central
      nervous system contains several factors blocking neurite outgrowth, inhibition of
      myelination by PACAP gives time for axonal development and synapse formation, and
      therefore, strengthens neuronal plasticity.

PMID- 21726626
TI  - Zebrafish embryos as an alternative to animal experiments--a commentary on the
      definition of the onset of protected life stages in animal welfare regulations.
AB  - Worldwide, the zebrafish has become a popular model for biomedical research and
      (eco)toxicology. Particularly the use of embryos is receiving increasing
      attention, since they are considered as replacement method for animal
      experiments. Zebrafish embryos allow the analysis of multiple endpoints ranging
      from acute and developmental toxicity determination to complex functional genetic
      and physiological analysis. Particularly the more complex endpoints require the
      use of post-hatched eleutheroembryo stages. According to the new EU Directive
      2010/63/EU on the protection of animals used for scientific purposes, the
      earliest life-stages of animals are not defined as protected and, therefore, do
      not fall into the regulatory frameworks dealing with animal experimentation.
      Independent feeding is considered as the stage from which free-living larvae are
      subject to regulations for animal experimentation. However, despite this
      seemingly clear definition, large variations exist in the interpretation of this
      criterion by national and regional authorities. Since some assays require the use
      of post-hatched stages up to 120 h post fertilization, the literature and
      available data are reviewed in order to evaluate if this stage could still be
      considered as non-protected according to the regulatory criterion of independent
      feeding. Based on our analysis and by including criteria such as yolk
      consumption, feeding and swimming behavior, we conclude that zebrafish larvae can
      indeed be regarded as independently feeding from 120 h after fertilization.
      Experiments with zebrafish should thus be subject to regulations for animal
      experiments from 120 h after fertilization onwards.

PMID- 21726627
TI  - Prolactin-stimulated activation of ERK1/2 mitogen-activated protein kinases is
      controlled by PI3-kinase/Rac/PAK signaling pathway in breast cancer cells.
AB  - There is strong evidence that deregulation of prolactin (PRL) signaling
      contributes to pathogenesis and chemoresistance of breast cancer. Therefore,
      understanding cross-talk between distinct signal transduction pathways triggered
      by activation of the prolactin receptor (PRL-R), is essential for elucidating the
      pathogenesis of metastatic breast cancer. In this study, we applied a sequential
      inhibitory analysis of various signaling intermediates to examine the hierarchy
      of protein interactions within the PRL signaling network and to evaluate the
      relative contributions of multiple signaling branches downstream of PRL-R to the
      activation of the extracellular signal-regulated kinases ERK1 and ERK2 in T47D
      and MCF-7 human breast cancer cells. Quantitative measurements of the
      phosphorylation/activation patterns of proteins showed that PRL simultaneously
      activated Src family kinases (SFKs) and the JAK/STAT, phosphoinositide-3 (PI3)
      kinase/Akt and MAPK signaling pathways. The specific blockade or siRNA-mediated
      suppression of SFK/FAK, JAK2/STAT5, PI3-kinase/PDK1/Akt, Rac/PAK or Ras
      regulatory circuits revealed that (1) the PI3-kinase/Akt pathway is required for
      activation of the MAPK/ERK signaling cascade upon PRL stimulation; (2) PI3-kinase
      mediated activation of the c-Raf-MEK1/2-ERK1/2 cascade occurs independent of
      signaling dowstream of STATs, Akt and PKC, but requires JAK2, SFKs and FAK
      activities; (3) activated PRL-R mainly utilizes the PI3-kinase-dependent Rac/PAK
      pathway rather than the canonical Shc/Grb2/SOS/Ras route to initiate and sustain
      ERK1/2 signaling. By interconnecting diverse signaling pathways PLR may enhance
      proliferation, survival, migration and invasiveness of breast cancer cells.

PMID- 21726628
TI  - Suppression of Polo like kinase 1 (PLK1) by p21(Waf1) mediates the p53-dependent
      prevention of caspase-independent mitotic death.
AB  - Polo-like kinase 1 (Plk1) plays key roles in many aspects of mitosis. We have
      previously shown that induction of p21(Waf1) by p53 is responsible for protection
      of cells against adriamycin-induced polyploidy formation and mitotic catastrophe.
      Here we show that adriamycin treatment suppressed Plk1 expression in a p53- and
      p21(Waf1)-dependent manner. Ablation of p21(Waf1) inhibited the adriamycin
      induced p53 activation, and this inhibition was alleviated by knockdown of Plk1,
      suggesting that p21(Waf1)-dependent suppression of Plk1 expression is responsible
      for maintaining p53 activation during stress response. Plk1 associated with p53
      and disrupted its interaction with target gene promoters in cells treated with
      adriamycin. Overexpression of Plk1 inhibited the p53-mediated prevention of
      caspase-independent mitotic death, but not polyploidy formation, in adriamycin
      treated cells. Together our results indicate that suppression of Plk1 by
      p21(Waf1) is responsible for p53-dependent protection against adriamycin-induced
      caspase-independent mitotic death.

PMID- 21726629
TI  - Phosphorylation of Y372 is critical for Jak2 tyrosine kinase activation.
AB  - Jak2 tyrosine kinase plays an important role in cytokine mediated signal
      transduction. There are 49 tyrosine residues in Jak2 and phosphorylation of some
      of these are known to play important roles in the regulation of Jak2 kinase
      activity. Here, using mass spectrometry, we identified tyrosine residues Y372 and
      Y373 as novel sites of Jak2 phosphorylation. Mutation of Y372 to F (Y372F)
      significantly inhibited Jak2 phosphorylation, including that of Y1007, whereas
      the Jak2-Y373F mutant displayed only modest reduction in phosphorylation.
      Relative to Jak2-WT, the ability of Jak2-Y372F to bind to and phosphorylate STAT1
      was decreased, resulting in reduced Jak2-mediated downstream gene transcription.
      While the Y372F mutation had no effect on receptor-independent, hydrogen peroxide
      mediated Jak2 activation, it impaired interferon-gamma (IFNgamma) and epidermal
      growth factor (EGF)-dependent Jak2 activation. Interestingly however, the Y372F
      mutant exhibited normal receptor binding properties. Finally, co-expression of
      SH2-Bbeta only partially restored the activation of the Jak2-Y372F mutant
      suggesting that the mechanism whereby phosphorylation of Y372 is important for
      Jak2 activation is via dimerization. As such, our results indicate that Y372
      plays a critical yet differential role in Jak2 activation and function via a
      mechanism involving Jak2 dimerization and stabilization of the active
      conformation.

PMID- 21726631
TI  - Antibiotic and metal resistance among hospital and outdoor strains of Pseudomonas
      aeruginosa.
AB  - Phenotypic analyses of antibiotic and metal resistance of a collection of 130
      strains of Pseudomonas aeruginosa from various outdoor (i.e. soil, water,
      animals) and hospital (environment, patients, individuals with cystic fibrosis)
      settings were performed. Resistance was scored according to the origin of the
      strains and their likely exposure to antibiotics and chemicals. Most of the 76
      outdoor strains showed a wild-type antibiotic resistance phenotype, i.e.
      resistance to minocycline and trimethoprim-sulfamethoxazole. Sixty percent of
      hospital strains showed a multiresistance phenotype (from 3 to 16 antibiotics)
      and confirmed that frequent exposure to antibiotics favored selection and
      maintenance of antibiotic resistance in P. aeruginosa. Twelve percent of outdoor
      strains naturally exposed to antiseptics and hydrocarbons showed significant
      resistance profiles, suggesting that chemical contaminants could contribute to
      selection of antibiotic resistance. For metal resistance, outdoor strains were
      more frequently resistant to zinc and cadmium, whereas hospital strains were more
      frequently resistant to mercury and copper. Differences in metal resistance
      between the 130 strains investigated were not related to previously characterized
      processes such as those implicating czcA, involved in cadmium, zinc, and cobalt
      resistance, or copA and copB, involved in copper resistance. Regulatory or new
      processes were likely to have contributed to the observed variations. Strains
      showing strong resistance to antibiotics were the least resistant to metals, and
      inversely. The lack of significant correlations between antibiotic and metal
      resistance suggests involvement of distinct processes that are rarely co
      selected. The effects of the P. aeruginosa collection size and multi-factorial
      selective pressure on data sets are discussed.

PMID- 21726630
TI  - Nuclear presence of nuclear factor of activated T cells (NFAT) c3 and c4 is
      required for Toll-like receptor-activated innate inflammatory response of
      monocytes/macrophages.
AB  - Nuclear factor of activated T cells (NFATs) are crucial transcription factors
      that tightly control proinflammatory cytokine expression for adaptive immunity in
      T and B lymphocytes. However, little is known about the role of NFATs for innate
      immunity in macrophages. In this study, we report that NFAT is required for Toll
      like receptor (TLR)-initiated innate immune responses in bone marrow-derived
      macrophages (BMMs). All TLR ligand stimulation including LPS, a TLR4 ligand, and
      Pam(3)CSK(4), a TLR1/2 ligand, induced expression of TNF which was inhibited by
      VIVIT, an NFAT-specific inhibitor peptide. BMMs from NFATc4 knock-out mouse
      expressed less TNF than wild type. Despite apparent association between NFAT and
      TNF, LPS did not directly activate NFAT based on NFAT-luciferase reporter assay,
      whereas NF-kappaB was inducibly activated by LPS. Instead, macrophage exhibited
      constitutive NFAT activity which was not increased by LPS and was decreased by
      VIVIT. Immunocytochemical examination of NFATc1-4 of BMMs exhibited nuclear
      localization of NFATc3/c4 regardless of LPS stimulation. LPS stimulation did not
      cause nuclear translocation of NFATc1/c2. Treatment with VIVIT resulted in
      nuclear export of NFATc3/c4 and inhibited TLR-activated TNF expression,
      suggesting that nuclear residence of NFATc is required for TLR-related innate
      immune response. Chromatin immunoprecipitation (ChIP) assay using anti-RNA
      polymerase II (PolII) antibody suggested that VIVIT decreased PolII binding to
      TNF gene locus, consistent with VIVIT inhibition of LPS-induced TNF mRNA
      expression. This study identifies a novel paradigm of innate immune regulation
      rendered by NFAT which is a well known family of adaptive immune regulatory
      proteins.

PMID- 21726632
TI  - Regulation of Wolbachia ankyrin domain encoding genes in Drosophila gonads.
AB  - The maternally inherited obligatory intracellular bacterium Wolbachia is a
      reproductive parasite of many insect species. Wolbachia evades the host immune
      system, uses the mitotic apparatus to ensure infection of daughter cells,
      migrates through the host to the gonads and causes reproductive phenotypes, most
      commonly cytoplasmic incompatibility (CI), i.e. incompatibility of sperm from
      infected males and eggs from uninfected females. Due to the interconnected facts
      that Wolbachia is not ex vivo culturable and that no established transformation
      system exists, virtually nothing is known about Wolbachia-host interactions at
      the macromolecular level. Intriguingly, the Wolbachia genome codes for an
      unusually high number of ankyrin repeat (ANK) proteins. ANKs mediate protein
      protein interactions in many different contexts. More common in eukaryotes, they
      also occur in prokaryotes. Some intracellular pathogenic bacteria export ANK
      effector proteins to the host cytoplasm. This makes the Wolbachia ANK genes
      candidates for mediating interactions with host cells. We quantified expression
      of ANK genes of Wolbachia strain wMel in adult gonads and detected host sex
      specific regulation of two wMel ANK genes in the gonads in two different
      backgrounds. Regulation was tissue-specific and independent of host background.
      We further analyzed expression of their homologues in strains wAu and wRi and
      found regulation only in wAu. Regulation was tissue-specific and there was no
      correlation between regulation of these genes and the ability of a strain to
      induce CI.

PMID- 21726633
TI  - Characterisation of a large family of polymorphic collagen-like proteins in the
      endospore-forming bacterium Pasteuria ramosa.
AB  - Collagen-like proteins containing glycine-X-Y repeats have been identified in
      several pathogenic bacteria potentially involved in virulence. Recently, a
      collagen-like surface protein, Pcl1a, was identified in Pasteuria ramosa, a spore
      forming parasite of Daphnia. Here we characterise 37 novel putative P. ramosa
      collagen-like protein genes (PCLs). PCR amplification and sequencing across 10 P.
      ramosa strains showed they were polymorphic, distinguishing genotypes matching
      known differences in Daphnia/P. ramosa interaction specificity. Thirty PCLs could
      be divided into four groups based on sequence similarity, conserved N- and C
      terminal regions and G-X-Y repeat structure. Group 1, Group 2 and Group 3 PCLs
      formed triplets within the genome, with one member from each group represented in
      each triplet. Maximum-likelihood trees suggested that these groups arose through
      multiple instances of triplet duplication. For Group 1, 2, 3 and 4 PCLs, X was
      typically proline and Y typically threonine, consistent with other bacterial
      collagen-like proteins. The amino acid composition of Pcl2 closely resembled
      Pcl1a, with X typically being glutamic acid or aspartic acid and Y typically
      being lysine or glutamine. Pcl2 also showed sequence similarity to Pcl1a and
      contained a predicted signal peptide, cleavage site and transmembrane domain,
      suggesting that it is a surface protein.

PMID- 21726634
TI  - Analysis of infant isolates of Bifidobacterium breve by comparative genome
      hybridization indicates the existence of new subspecies with marked infant
      specificity.
AB  - A total of 20 Bifidobacterium strains were isolated from fecal samples of 4
      breast- and bottle-fed infants and all were characterized as Bifidobacterium
      breve based on 16S rRNA gene sequence and metabolic analysis. These isolates were
      further characterized and compared to the type strains of B. breve and 7 other
      Bifidobacterium spp. by comparative genome hybridization. For this purpose, we
      constructed and used a DNA-based microarray containing over 2000 randomly cloned
      DNA fragments from B. breve type strain LMG13208. This molecular analysis
      revealed a high degree of genomic variation between the isolated strains and
      allowed the vast majority to be grouped into 4 clusters. One cluster contained a
      single isolate that was virtually indistinguishable from the B. breve type
      strain. The 3 other clusters included 19 B. breve strains that differed
      considerably from all type strains. Remarkably, each of the 4 clusters included
      strains that were isolated from a single infant, indicating that a niche
      adaptation may contribute to variation within the B. breve species. Based on
      genomic hybridization data, the new B. breve isolates were estimated to contain
      approximately 60-90% of the genes of the B. breve type strain, attesting to the
      existence of various subspecies within the species B. breve. Further
      bioinformatic analysis identified several hundred diagnostic clones specific to
      the genomic clustering of the B. breve isolates. Molecular analysis of
      representatives of these revealed that annotated genes from the conserved B.
      breve core encoded mainly housekeeping functions, while the strain-specific genes
      were predicted to code for functions related to life style, such as carbohydrate
      metabolism and transport. This is compatible with genetic adaptation of the
      strains to their niche, a combination of infants and diet.

PMID- 21726635
TI  - Lipophilicity of zwitterions and related species: a new insight.
AB  - The experimental determination of microscopic partition coefficients for
      protonation isomers is elaborated for the first time, and applied for niflumic
      acid, an ampholytic, mainly zwitterionic drug for pains in joints and muscles.
      The acid-base microequilibria of niflumic acid are also characterized by NMR-pH
      and deductive methods using auxiliary compounds of reduced complexity. The
      results show that 16 times as many zwitterionic than non-charged microspecies
      exist in aqueous solution. Partition of the individual microspecies was mimicked
      by model compounds of the closest possible similarity, then correction factors
      were also determined and introduced. Thus the long-awaited intrinsic partition
      coefficients of the non-charged vs. zwitterionic species could be calculated. The
      non-charged microspecies is 390 times as lipophilic as its zwitterionic
      protonation isomer. The microscopic partition coefficients are also in line with
      the experimentally determined distribution coefficients. These results make
      evident that contribution of the zwitterionic microspecies to the overall
      lipophilicity is not negligible, especially at the isoelectric pH region of the
      compound.

PMID- 21726636
TI  - Chemoembolization agents for cancer treatment.
AB  - Chemoembolization has been used in the field of interventional oncology. Although
      practiced widely, it has only recently been demonstrated that the use of
      transarterial chemoembolization (TACE) provides a survival benefit based on
      randomized controlled trials. TACE combines the effect of targeted chemotherapy
      with the effect of ischemic necrosis induced by arterial embolization. Most of
      the TACE procedures have been based on iodized oil utilizing its microembolic and
      drug-carrying characteristics. Recently, there have been efforts to improve the
      delivery of chemotherapeutic agents to a tumor, which leads to the development of
      drug-eluting particles. In this review, we will describe the properties and
      efficacy of some chemoembolization agents which are commercially available and/or
      currently under clinical investigations. The potential and future of this new
      form of transcatheter arterial therapy for liver cancer will be discussed.

PMID- 21726637
TI  - Perfusion calorimetry in the characterization of solvates forming isomorphic
      desolvates.
AB  - In this study, the potential of perfusion calorimetry in the characterization of
      solvates forming isomorphic desolvates was investigated. Perfusion calorimetry
      was used to expose different hydrates forming isomorphic desolvates (emodepside
      hydrates II-IV, erythromycin A dihydrate and spirapril hydrochloride monohydrate)
      to stepwise increasing relative vapour pressures (RVP) of water and methanol,
      respectively, while measuring thermal activity. Furthermore, the suitability of
      perfusion calorimetry to distinguish the transformation of a desolvate into an
      isomorphic solvate from the adsorption of solvent molecules to crystal surfaces
      as well as from solvate formation that is accompanied by structural rearrangement
      was investigated. Changes in the samples were confirmed using FT-Raman and FT-IR
      spectroscopy. Perfusion calorimetry indicates the transformation of a desolvate
      into an isomorphic solvate by a substantial exothermic, peak-shaped heat flow
      curve at low RVP which reflects the rapid incorporation of solvent molecules by
      the desolvate to fill the structural voids in the lattice. In contrast,
      adsorption of solvent molecules to crystal surfaces is associated with distinctly
      smaller heat changes whereas solvate formation accompanied by structural changes
      is characterized by an elongated heat flow. Hence, perfusion calorimetry is a
      valuable tool in the characterization of solvates forming isomorphic desolvates
      which represents a new field of application for the method.

PMID- 21726638
TI  - Improvement of an encapsulation process for the preparation of pro- and
      prebiotics-loaded bioadhesive microparticles by using experimental design.
AB  - The purpose of this study was to design a new vaginal bioadhesive delivery system
      based on pectinate-hyaluronic acid microparticles for probiotics and prebiotics
      encapsulation. Probiotic strains and prebiotic were selected for their abilities
      to restore vaginal ecosystem. Microparticles were produced by
      emulsification/gelation method using calcium as cross-linking agent. In the first
      step, preliminary experiments were conducted to study the influence of the main
      formulation and process parameters on the size distribution of unloaded
      microparticles. Rheological measurements were also performed to investigate the
      bioadhesive properties of the gels used to obtain the final microparticles.
      Afterwards an experimental design was performed to determine the operating
      conditions suitable to obtain bioadhesive microparticles containing probiotics
      and prebiotics. Experimental design allowed us to define two important parameters
      during the microencapsulation process: the stirring rate during the
      emulsification step and the pectin concentration. The final microparticles had a
      mean diameter of 137MUm and allowed a complete release of probiotic strains after
      16h in a simulated vaginal fluid at +37 degrees C.

PMID- 21726639
TI  - Structural properties of so-called NSAID-phospholipid-complexes.
AB  - So-called NSAID-phospholipid-complexes have been recently reported in literature
      to reduce local gastrointestinal toxicity. The present work was dedicated to the
      structural characterization of so-called drug-phospholipid-complexes on the
      example of diclofenac sodium, ibuprofen and piroxicam complexes with
      dipalmitoylphosphatidylcholine (DPPC) at different stages of preparation. The
      applied techniques include (1)H/2D ROESY NMR for the structural characterization
      in organic solvents, FT-IR and X-ray diffraction for the structural
      characterization in the solid state and PCS, (31)P NMR, as well as MAS (1)H/2D
      NOESY NMR for the structural characterization in aqueous media following
      hydration. Whereas the formation of isolated 1:1 drug-phospholipid-complexes with
      a preferential location of diclofenac and ibuprofen at the polar head group,
      stabilized by cation-pi interaction, seems reasonable in organic solvents, it was
      found that mainly liposomal and micellar structures are formed upon hydration of
      the drug-phospholipid-complexes. Hence the term "NSAID-phospholipid-complex" may
      be misleading in the context with physiologically relevant aqueous media.
      Piroxicam did not show significant interaction with DPPC.

PMID- 21726640
TI  - Product and process understanding of a novel pediatric anti-HIV tenofovir
      niosomes with a high-pressure homogenizer.
AB  - A variety of factors were systemically evaluated in order to establish the
      characteristics of the niosomes obtained with a high-pressure homogenizer. The
      vesicular sizing parameters, electrical properties, drug entrapment data and drug
      release characteristics were investigated using two groups of factors. The first
      group presented the physical process variables such as pressure of the
      homogenizer and the times that the samples were processed (cycles). The second
      group encompassed the compositional variables such as the drug loading,
      surfactant chain length, cholesterol level and the level of the charge imparting
      agent. The obtained data showed that the drug distributed within both the aqueous
      and lipid phases of the formed niosomes. Saturation-like behaviors for both the
      effect of homogenization cycles on the produced size and the effect of the
      pressure on the size homogeneity were recorded. In contrast to the drug
      entrapment and conductivity of the niosomal suspension, the vesicular size
      parameters as well as the zeta potential were inversely proportional with the
      homogenization parameters. Drug release was significantly affected by the
      compositional factors rather than the physical ones. The current study
      demonstrated the usefulness of the microfluidization for the production and
      further scale-up of anti-HIV niosomes with very small mean vesicular sizes.

PMID- 21726641
TI  - Understanding the mechanism of protamine in solid lipid nanoparticle-based
      lipofection: the importance of the entry pathway.
AB  - The aim of our study was to evaluate the effect of protamine on the transfection
      capacity of solid lipid nanoparticles (SLNs) by correlating it to the
      internalization mechanisms and intracellular trafficking of the vectors. Vectors
      were prepared with SLN, DNA, and protamine. ARPE-19 and HEK-293 cells were used
      for the evaluation of the formulations. Protamine induced a 6-fold increase in
      the transfection of SLNs in retinal cells due to the presence of nuclear
      localization signals (NLS), its protection capacity, and a shift in the
      internalization mechanism from caveolae/raft-mediated to clathrin-mediated
      endocytosis. However, protamine produced an almost complete inhibition of
      transfection in HEK-293 cells. In spite of the high DNA condensation capacity of
      protamine and its content in NLS, this does not always lead to an improvement in
      cell transfection since it may impair some of the limiting steps of the
      transfection processes.

PMID- 21726642
TI  - The suppressive effect of mesenchymal stromal cells on T cell proliferation is
      conserved in old age.
AB  - Mesenchymal stromal cells (MSC) have become a useful tool in curing graft versus
      host disease (GVHD) after transplantation. No information is presently available
      whether the immunosuppressive properties of this cell type are maintained in old
      age. It was therefore the aim of our study to analyze the immunoregulatory effect
      of MSC on peripheral blood mononuclear cells (PBMC) in old age. We studied the
      proliferation, activation and cytokine production of PBMC following co-culture
      with MSC from young (<30 years) and old (>61 years) donors. Our results
      demonstrate that MSC from elderly donors exhibit the same suppressive effects on
      T cell proliferation as their young counterparts. In both age groups T cell
      activation was not influenced by co-culture with MSC from young and elderly
      donors. With the exception of IL-6, cytokine production by unstimulated or
      stimulated PBMC was also not affected by MSC from either age group. IL-6
      production was increased during co-culture of PBMC and MSC and was higher when
      MSC from elderly donors were used. After PHA stimulation, however, this age
      specific difference was balanced and appeared even. As high IL-6 production is a
      prerequisite for an effective suppression of T cell proliferation, MSC can be
      considered a powerful tool for immunoregulatory therapies in old age.

PMID- 21726643
TI  - Substance P receptor activation induces downregulation of the AMPA receptor
      functionality in cortical neurons from a genetic model of Amyotrophic Lateral
      Sclerosis.
AB  - Substance P (SP), a neuropeptide member of the tachykinin (TK) family, has a
      functional role both in physiological and pathological conditions, including
      Amyotrophic Lateral Sclerosis disease. One hypothesis of the selective motor
      neuron death in ALS involves the excitatory neurotransmitter glutamate, because
      these neurons are extremely susceptible to excessive stimulation of AMPA
      receptors. It has been reported that SP exerts its action against a variety of
      insults including excitotoxicity, and that altered levels of SP have been
      observed in the cerebrospinal fluid (CSF) of patients with ALS. Here we have
      analyzed the interaction between SP and AMPA receptor functionality, both in
      Control cortical neurons in culture and in those obtained from a genetic mouse
      model of ALS (G93A). Our studies demonstrate that SP reduces the kainate
      activated currents in Control and G93A neurons and that this reduction is
      significantly higher in the mutated neurons. SP effect is mediated by its
      receptor NK1 because GR 82334 (5 MUM), a NK1 competitive antagonist, is able to
      suppress the current reduction. Analysis of miniature excitatory postsynaptic
      currents (mEPSCs) in Control and G93A neurons indicates that SP (200 nM) is able
      to significantly decrease the mEPSC amplitudes in G93A neurons, whereas it is
      ineffective on Control mEPSCs. Western blotting experiments in cultures and
      cortical tissues show a higher NK1 expression level in G93A mice compared to that
      of Control. This is also confirmed by immunocytochemistry experiments in cultured
      neurons. In addition, the amount of GluR1 subunit AMPA receptors is not modified
      following SP exposure, indicating a non internalization of the AMPA receptors.
      Finally, toxicity experiments have revealed that SP is able to rescue G93A
      cortical cells whereas it is ineffective on those of Control. These findings
      provide the first evidence of SP having a physiological and protective role in
      the G93A mouse model of ALS, and may suggest the possible use of SP as a clinical
      therapeutic treatment.

PMID- 21726644
TI  - Dysregulation of SREBP2 induces BACE1 expression.
AB  - beta-Amyloid hyperproduction has been observed in response to alterations in
      neuronal intracellular cholesterol storage, efflux, and synthesis, induced in
      rats by a high-fat diet. It has been suggested that cholesterol homeostasis is
      altered in Alzheimer's disease resulting in higher beta- and gamma-secretase
      activity. In the current study the neuronal activation status of sterol
      regulatory element binding protein 2 (SREBP2) as well as its involvement in beta
      secretase BACE1 activity was investigated in high-fat fed rats (26% fat and 4%
      cholesterol for 20 weeks), and in SK-N-BE neuroblastoma cells exposed to 20 MUM
      cholesterol. This work demonstrates that in the brain a hyperlipidic diet is able
      to induce a hyper-expression of BACE1 and determine an unbalance in cerebral
      cholesterol homeostasis so that SREBP2 is activated. In addition, we show for the
      first time the involvement of SREBP2 on expression of BACE1 in SK-N-BE cells
      exposed to high cholesterol. Although the enhanced risk of Alzheimer's disease in
      metabolic syndrome is related to several factors, our results suggest that
      SREBP2, which can be modulated by the impairment of cerebral cholesterol
      homeostasis, has a direct role on BACE1 expression and may be involved in
      Alzheimer's disease progression.

PMID- 21726645
TI  - Obesity and downregulated hypothalamic leptin receptors in male metallothionein-3
      null mice.
AB  - In the present study, we examined whether metallothionein-3 (Mt3), a zinc-binding
      protein that is specifically enriched in a brain, plays a role in obesity and
      hypothalamic leptin signaling in mice. Upon aging, male Mt3-null mice gained more
      body weight than male wild-type mice; however, the daily amount of food intake
      was little different. Rather, the obesity in male Mt3-null mice was likely the
      result of decreased metabolic rates, as indicated by lower oxygen consumption and
      carbon dioxide production. Consistent with this, mRNA levels for the
      mitochondrial proton carrier UCP1 were reduced in brown adipose tissue of Mt3
      null mice. Although Mt3-null mice showed increases in serum leptin levels,
      probably due to increased fat mass, the level of the leptin receptor (Lepr) in
      the hypothalamus of these mice was significantly reduced. In addition, levels of
      phosphorylated extracellular signal-regulated kinase (p-Erk-1/2) were also
      reduced in the hypothalamus of Mt3-null mice. Because zinc released from Mt3 may
      activate Erk-1/2, we examined whether zinc is involved in the upregulation of
      Lepr levels through the activation of Erk-1/2. Consistent with this possibility,
      exposure of hypothalamic cells to zinc activated Erk-1/2 and induced Lepr
      expression in an Erk-dependent manner. The present results demonstrate that Mt3
      in the brain of male mice, particularly in the hypothalamus, may be involved in
      central leptin signaling and the consequent increase in peripheral energy
      expenditure. In addition to providing insight into the role of zinc and
      metallothioneins in the development of obesity, this new information may help
      design ways to overcome the pervasive problem of obesity.

PMID- 21726646
TI  - Developmental profile and regulation of the glycolytic enzyme hexokinase 2 in
      normal brain and glioblastoma multiforme.
AB  - Highly proliferating cells, normal or transformed, undergo aerobic glycolysis
      whereby glucose is metabolized to lactate rather than by oxidative metabolism,
      even in the presence of oxygen. This metabolic adaptation provides a survival
      advantage and facilitates synthesis of biosynthetic precursors required for
      continued cellular proliferation. An important mediator of aerobic glycolysis is
      our demonstration that in malignant gliomas there is over-expression of the
      glycolytic enzyme hexokinase 2 (HK2), phosphorylating glucose as the first step
      of the glycolytic pathway. In contrast, normal brain preferentially expresses HK1
      and undergoes oxidative glucose metabolism. In this study, we examine whether
      this switch in HK isoform also occurs in the developing embryo and central
      nervous system (CNS). Bioinformatic analysis of available microarray data,
      including that of The Cancer Genome Atlas, demonstrated a ~17% overlap in
      metabolic-related genes in blastocyst stage embryo and human GBM tissue,
      including upregulation of HK2 and downregulation of HK1. Quantitative RT-PCR on
      mouse brains isolated at different embryonic and postnatal development time
      points demonstrated HK2 expression was highest in the early embryo, while HK1
      expression increased with CNS maturation. The downstream glycolytic enzymes PKM2
      and LDHA had similar temporal profiles as HK2. Expression of the HK2 isoform was
      due in part to epigenetic regulation of HK2. In support, adult normal human brain
      and the few human GBM cell lines with low HK2 expression had methylation of CpG
      islands within intron 1 of HK2. In contrast, developing human fetal brain and GBM
      tissue expressing HK2 demonstrated significantly lower percent methylation.
      Furthermore, treatment of GBM cells lacking HK2 with 5-aza-2-deoxycytidine
      restored HK2 transcript expression. Overall, our results demonstrate that
      proliferative states including the developing embryo and malignant gliomas, which
      rely on aerobic glycolysis, preferentially express the HK2 isoform, found to be
      regulated in part epigenetically.

PMID- 21726647
TI  - AAV-mediated netrin-1 overexpression increases peri-infarct blood vessel density
      and improves motor function recovery after experimental stroke.
AB  - Apart from its role in axon guidance, netrin-1 is also known to be pro
      angiogenic. The aim of this study is to determine whether adeno-associated viral
      (AAV) mediated overexpression of netrin-1 improves post-stroke neurovascular
      structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of 1*10(10) genome
      copies each was injected medial and posterior to ischemic lesion at one hour
      following reperfusion using the distal middle cerebral artery occlusion (MCAO)
      method. Quantitative RT-PCR revealed that the expression of netrin-1 transgene
      began as early as one day and increased dramatically about 3 weeks following
      vector injection. Western blot analysis and confocal microscopy suggested that
      both the endogenous and transduced netrin-1 were expressed in the neurons of the
      peri-infarct cortex after MCAO. AAV-mediated netrin-1 overexpression
      significantly increased vascular density in the peri-infarct cortex and promoted
      the migration of immature neurons into the peri-infarct white matter, but it did
      not significantly reduce infarct size. Netrin-1 overexpression also enhanced post
      stroke locomotor activity, improved exploratory behavior, and reduced ischemia
      induced motor asymmetry in forelimb usage. However, it had little effect on post
      stroke spatial learning and memory. Our results suggest that AAV mediated netrin
      1 overexpression improves peri-infarct vascular density and post stroke motor
      function.

PMID- 21726648
TI  - An MEG signature corresponding to an axiomatic model of reward prediction error.
AB  - Optimal decision-making is guided by evaluating the outcomes of previous
      decisions. Prediction errors are theoretical teaching signals which integrate two
      features of an outcome: its inherent value and prior expectation of its
      occurrence. To uncover the magnetic signature of prediction errors in the human
      brain we acquired magnetoencephalographic (MEG) data while participants performed
      a gambling task. Our primary objective was to use formal criteria, based upon an
      axiomatic model (Caplin and Dean, 2008a), to determine the presence and timing
      profile of MEG signals that express prediction errors. We report analyses at the
      sensor level, implemented in SPM8, time locked to outcome onset. We identified,
      for the first time, a MEG signature of prediction error, which emerged
      approximately 320 ms after an outcome and expressed as an interaction between
      outcome valence and probability. This signal followed earlier, separate signals
      for outcome valence and probability, which emerged approximately 200 ms after an
      outcome. Strikingly, the time course of the prediction error signal, as well as
      the early valence signal, resembled the Feedback-Related Negativity (FRN). In
      simultaneously acquired EEG data we obtained a robust FRN, but the win and loss
      signals that comprised this difference wave did not comply with the axiomatic
      model. Our findings motivate an explicit examination of the critical issue of
      timing embodied in computational models of prediction errors as seen in human
      electrophysiological data.

PMID- 21726649
TI  - Assessing language and visuospatial functions with one task: a "dual use"
      approach to performing fMRI in children.
AB  - In order to increase the rate of successful functional MR studies in children it
      is helpful to shorten the time spent in the scanner. To this effect, assessing
      two cognitive functions with one task seems to be a promising approach. The
      hypothesis of this study was that the control condition of an established
      language task (vowel identification task, VIT) requires visuospatial processing
      and that the control condition (VIT(CC)) therefore may also be applicable to
      localize visuospatial functions. As a reference task, a visual search task (VST,
      previously established for use in children) was employed. To test this
      hypothesis, 43 children (19 f, 24 m; 12.0+/-2.6, range 7.9 to 17.8 years) were
      recruited and scanned using both tasks. Second-level random effects group
      analyses showed activation of left inferior-frontal cortex in the active
      condition of the VIT, as in previous studies. Additionally, analysis of the
      VIT(CC) demonstrated activation in right-dominant superior parietal and high
      frontal brain regions, classically associated with visuospatial functions;
      activation seen in the VST was similar with a substantial overlap. However,
      lateralization in the parietal lobe was significantly more bilateral in the VST
      than in the VIT(CC). This suggests that the VIT can not only be applied to assess
      language functions (using the active>control contrast), but also that the
      control>active condition is useful for assessing visuospatial functions. Future
      task design may benefit from such a "dual use" approach to performing fMRI not
      only, but also particularly in children.

PMID- 21726650
TI  - Mirtazapine antagonises the subjective, hormonal and neuronal effects of m
      chlorophenylpiperazine (mCPP) infusion: a pharmacological-challenge fMRI (phMRI)
      study.
AB  - Aberrant signalling through central 5-HT(2C) receptor pathways has been
      implicated in various psychiatric disorders but this has not been amenable to
      experimental investigation in the absence of a valid in-vivo biomarker of
      functional 5-HT(2C) neurotransmission. One approach is drug-challenge pharmaco
      magnetic resonance imaging (phMRI). We have previously shown that intravenous
      administration of the 5-HT(2C) agonist m-chlorophenylpiperazine (mCPP) elicits
      increases in blood oxygenation dependent signal (BOLD) in regions consistent with
      the distribution of 5-HT(2C) receptors. In the current study we determined
      whether BOLD signal responses to mCPP could be blocked by pre-treatment with a 5
      HT(2C) antagonist. Healthy male volunteers received oral mirtazapine, 5-HT(2)/5
      HT(3) receptor antagonist, or placebo 90min prior to intravenous mCPP challenge
      phMRI. BOLD signal increases following mCPP infusion occurred in areas known to
      be rich in 5-HT(2C) receptors such as the substantia nigra, hypothalamus,
      pallidum and amygdala. These responses were attenuated by mirtazapine pre
      treatment. The results suggest that mCPP-challenge phMRI produces reliable
      patterns of response that are mediated by 5-HT(2C) receptors; these responses may
      therefore be useful in-vivo measures of 5-HT(2C) function in psychiatric
      disorders.

PMID- 21726651
TI  - Maturation of obligatory auditory responses and their neural sources: evidence
      from EEG and MEG.
AB  - Neural auditory responses are known to change from childhood to adulthood. The
      most prominent components of the event-related potentials (ERPs) found in
      children are the P1 and N2, while the P1 and N1 are strongest in adults. Previous
      dipole localizations showed regions of the auditory cortex (AC) underlying these
      responses. An N1 in children, however, has only been observed in older age or
      under certain experimental conditions different than commonly applied in adults.
      The current study aimed to further elucidate on auditory processing and related
      components in school-aged children. To do this, MEG and EEG was recorded in
      adults and 9 to 10year old children, while presenting pure tones either
      repetitively or randomly among tones of different pitch. Furthermore, the current
      paradigm was explicitly designed to not only investigate the P1 and N2 in
      children, but moreover to examine N1 modulations based on different refractory
      states caused by the two conditions. Our results are clear cut. In adults, P1(m)
      and N1(m) components were localized in AC regions, with the N1(m) largely
      attenuated for repetitive tones. The P1(m) and N2(m) components observed in
      children were also localized in AC regions. Most importantly, ERP modulations in
      the N1 time window (i.e., larger responses for random than repetitive tones) were
      remarkably similar for adults and children, both in amplitude and latency. This
      effect indicates that the N1 sub-component reflecting frequency-specific
      refractoriness is fully developed in 9 to 10year old children. Thus, previous
      interpretations on the function and maturation of the N1 need reconsideration.

PMID- 21726652
TI  - Parcellation of human amygdala in vivo using ultra high field structural MRI.
AB  - Histological studies show that human amygdala is subdivided into several nuclei
      with specific connections to other brain areas. One such study has been recently
      used as the basis of a probabilistic amygdala map, to enable in vivo
      identification of specifically located functions within the amygdala and
      connections to it. The involvement of the amygdala in cognition, emotion and
      action, which may underlie several psychiatric disorders, points to a need for
      discrimination of these nuclei in living human brains using different techniques.
      Structural MRI scans of the human amygdala at standard field strengths (<=3 T)
      have shown a region of generally featureless gray matter. Apparently homogeneous
      regions may reveal internal structure, however, when improved imaging strategies
      and better SNR are available. The goal of this study is the in vivo anatomical
      segmentation of the amygdala using high resolution structural MR data. The use of
      different MRI tissue contrast mechanisms at high field strengths has been little
      explored so far. Combining two different contrasts, and using cutting-edge image
      analysis, the following study provides a robust clustering of three amygdala
      components in vivo using 7 T structural imaging.

PMID- 21726653
TI  - Model-based dynamical analysis of functional disconnection in schizophrenia.
AB  - Schizophrenia is shown to be associated with impaired interactions in functional
      macro-networks of the brain. The focus of our study was if there is an impairment
      of cognitive control of learning during schizophrenia. To investigate this
      question, we collected fMRI data from a group of stable schizophrenia patients
      and controls performing an object-location associative learning task in which the
      learning performance of the patient group was significantly worse. We applied
      Dynamic Causal Modeling to analyze the fMRI data. A set of causal models of BOLD
      signal generation was defined to evaluate connections between five regions
      material to the task (Primary Visual Cortex, Superior Parietal and Inferior
      Temporal Cortex, Hippocampus and Dorsal Prefrontal Cortex). Bayesian model
      selection was used to investigate hypotheses on differences in model architecture
      across groups, and indicated fundamental differences in model architecture in
      patients compared to controls. Models lacking connections related to cognitive
      control were more probable in the patient group. Hypotheses on differences in
      effective connectivity between groups were tested by comparing estimates of
      neural coupling parameters in winning model structures. This analysis indicated
      reduced fronto-hippocampal and hippocampo-inferior temporal coupling in patients,
      and reduced excitatory modulation of these pathways by learning. These findings
      may account for the documented reductions in learning performance of
      schizophrenia patients.

PMID- 21726654
TI  - Identification and analysis of the Shewanella oneidensis major oxygen-independent
      coproporphyrinogen III oxidase gene.
AB  - Shewanella oneidenesis MR-1 is a facultative anaerobe that can use a large number
      of electron acceptors including metal oxides. During anaerobic respiration, S.
      oneidensis MR-1 synthesizes a large number of c cytochromes that give the
      organism its characteristic orange color. Using a modified mariner transposon, a
      number of S. oneidensis mutants deficient in anaerobic respiration were
      generated. One mutant, BG163, exhibited reduced pigmentation and was deficient in
      c cytochromes normally synthesized under anaerobic condition. The deficiencies in
      BG163 were due to insertional inactivation of hemN1, which exhibits a high degree
      of similarity to genes encoding anaerobic coproporphyrinogen III oxidases that
      are involved in heme biosynthesis. The ability of BG163 to synthesize c
      cytochromes under anaerobic conditions, and to grow anaerobically with different
      electron acceptors was restored by the introduction of hemN1 on a plasmid.
      Complementation of the mutant was also achieved by the addition of hemin to the
      growth medium. The genome sequence of S. oneidensis contains three putative
      anaerobic coproporphyrinogen III oxidase genes. The protein encoded by hemN1
      appears to be the major enzyme that is involved in anaerobic heme synthesis of S.
      oneidensis. The other two putative anaerobic coproporphyrinogen III oxidase genes
      may play a minor role in this process.

PMID- 21726655
TI  - Effect of non-thermal processing by High Hydrostatic Pressure on the survival of
      probiotic microorganisms: study on Bifidobacteria spp.
AB  - High Hydrostatic Pressure (HP) processing has been suggested as an alternative
      method to improve textural attributes of dairy products. Since, the global market
      seeks improved functional foods, it is important to investigate whether HP
      processing can be applied to fermented dairy probiotic products. The inactivation
      kinetics of Bifidobacterium spp. in a model system of acid pH value under high
      pressure (100-400 MPa) combined with moderate temperature (20-35 degrees C) was
      investigated. Bifidobacterium spp. inactivation followed first order kinetics at
      all pressure-temperature combinations used. Pressure and temperature were found
      to act synergistically on the viability loss of the bacterium. The corresponding
      z(T) and z(P) values of inactivation were also estimated and, values of 41.5
      degrees C and 93.5 MPa at reference pressure of 200 MPa and reference temperature
      of 25 degrees C were estimated, respectively. HP treatment of 200 MPa at 20-25
      degrees C for 10-15 min, recommended for textural modification, is not
      detrimental to the viability of the studied probiotic culture and would be
      suitable for respective fermented probiotic products.

PMID- 21726657
TI  - Aerobic training stimulates growth and promotes disease resistance in Atlantic
      salmon (Salmo salar).
AB  - Improving fish robustness is of utmost relevance to reducing fish losses in
      farming. Although not previously examined, we hypothesized that aerobic training,
      as shown for human studies, could strengthen disease resistance in Atlantic
      salmon (Salmo salar). Thus, we exercised salmon pre-smolts for 6 weeks at two
      different aerobic training regimes; a continuous intensity training (CT; 0.8bls(
      1)) and an interval training (IT; 0.8bl s(-1) 16h and 1.0bl s(-1) 8h) and
      compared them with untrained controls (C; 0.05bl s(-1)). The effects of endurance
      training on disease resistance were evaluated using an IPN virus challenge test,
      while the cardiac immune modulatory effects were characterized by qPCR and
      microarray gene expression analyses. In addition, swimming performance and growth
      parameters were investigated. Survival after the IPN challenge was higher for IT
      (74%) fish than for either CT (64%) or C (61%) fish. While both CT and IT groups
      showed lower cardiac transcription levels of TNF-alpha, IL-1beta and IL-6 prior
      to the IPN challenge test, IT fish showed the strongest regulation of genes
      involved in immune responses and other processes known to affect disease
      resistance. Both CT and IT regimes resulted in better growth compared with
      control fish, with CT fish developing a better swimming efficiency during
      training. Overall, interval aerobic training improved growth and increased
      robustness of Atlantic salmon, manifested by better disease resistance, which we
      found was associated with a modulation of relevant gene classes on the cardiac
      transcriptome.

PMID- 21726656
TI  - Non-toxigenic Clostridium sordellii: clinical and microbiological features of a
      case of cholangitis-associated bacteremia.
AB  - Toxigenic Clostridium sordellii strains are increasingly recognized to cause
      highly lethal infections in humans that are typified by a toxic shock syndrome
      (TSS). Two glucosylating toxins, lethal toxin (TcsL) and hemorrhagic toxin (TcsH)
      are believed to be important in the pathogenesis of TSS. While non-toxigenic
      strains of C. sordellii demonstrate reduced cytotoxicity in vitro and lower
      virulence in animal models of infection, there are few data regarding their
      behavior in humans. Here we report a non-TSS C. sordellii infection in the
      context of a polymicrobial bacterial cholangitis. The C. sordellii strain
      associated with this infection did not carry either the TcsL-encoding tcsL gene
      or the tcsH gene for TcsH. In addition, the strain was neither cytotoxic in vitro
      nor lethal in a murine sepsis model. These results provide additional correlative
      evidence that TcsL and TcsH increase the risk of mortality during C. sordellii
      infections.

PMID- 21726658
TI  - The Omega-3 Index as a risk factor for cardiovascular diseases.
AB  - The Omega-3 Index has been defined as eicosapentaenoic plus docosahexaenoic acids
      in erythrocytes. Integral part of the definition is a standardized analytical
      procedure, which conforms to the standards of Clinical Chemistry. This resulted
      in more than 90 collaborative research projects, concluded and ongoing, and 64
      publications so far. The Omega-3 Index is emerging as a risk factor for fatal and
      non-fatal cardiovascular events. This standardized analysis of fatty acid
      patterns adds incremental information to standard risk factor algorithms, and it
      correctly reclassifies persons from intermediate to high or low risk.
      Circumstantial evidence indicates that determining the Omega-3 Index has a
      therapeutic consequence. Thus, the Omega-3 Index fulfils important criteria for
      novel biomarkers, set forth by the American Heart Association and others, and
      compares well to other novel biomarkers. Future results will add precision to the
      value of the Omega-3 Index in cardiology, and probably expand its application to
      other areas, like psychiatry and pregnancy.

PMID- 21726659
TI  - The combined use of Paracoccidioides brasiliensis Pb40 and Pb27 recombinant
      proteins enhances chemotherapy effects in experimental paracoccidioidomycosis.
AB  - Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis
      (PCM), a chronic granulomatous mycosis prevalent in Latin America, and cell
      mediated immunity represents the main mode of protection against this fungal
      infection. The conventional treatment for this mycosis involves long periods of
      therapy resulting in sequels and a high frequency of relapse. The search for new
      alternative methods of treatment is thus necessary. With this aim, the objective
      of this work was to evaluate the potential of rPb27 and rPb40 immunization to
      reduce treatment length and the frequency of relapse when used as an adjuvant to
      fluconazole chemotherapy in experimental PCM. Combined treatment with the drug
      and the two proteins reduced CFUs in the lung, liver and spleen to undetectable
      levels and largely preserved the tissue structure of these organs. At the same
      time, IFN-gamma and TNF-alpha levels were higher in mice treated as described
      above than in infected-only mice, while very low production of IL-10 and TGF-beta
      was observed in this treated group. Thus, the combined treatment, using
      immunization with the two recombinant proteins in addition to fluconazole
      chemotherapy, showed an additive protective effect after intratracheal challenge.
      These results provide new prospects for immunotherapy as a treatment for PCM.

PMID- 21726660
TI  - Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease.
AB  - Trypanosoma cruzi the cause of Chagas disease persists in tissues of infected
      experimental animals and humans. Here we demonstrate the persistence of the
      parasite in adipose tissue from of three of 10 elderly seropositive patients with
      chronic chagasic heart disease. Nine control patients had no parasites in the
      fat. We also demonstrate that T. cruzi parasitizes primary adipocytes in vitro.
      Thus, in humans as in mice the parasite may persist in adipose tissue for decades
      and become a reservoir of infection.

PMID- 21726661
TI  - The HepaRG cell line is suitable for bioartificial liver application.
AB  - For bioartificial liver application, cells should meet the following minimal
      requirements: ammonia elimination, drug metabolism and blood protein synthesis.
      Here we explore the suitability of HepaRG cells, a human cell line reported to
      differentiate into hepatocyte clusters and surrounding biliary epithelial-like
      cells at high density and after exposure to dimethyl sulfoxide (DMSO). The effect
      of carbamoyl-glutamate (CG), an activator of urea cycle enzyme carbamoylphosphate
      synthetase (CPS) was studied additionally. The effects of DMSO and/or CG were
      assessed in presence of (15)NH(4)Cl on HepaRG cells in monolayer. We tested
      hepatocyte-specific functions at transcript and biochemical level, cell damage
      parameters and performed immunostainings. Ureagenesis, ammonia/galactose
      elimination and albumin, glutamine synthetase and CPS transcript levels were
      higher in -DMSO than +DMSO cultures, probably due to a higher cell content and/or
      cluster-neighbouring regions contributing to their functionality. DMSO treatment
      increased cytochrome P450 (CYP) transcript levels and CYP3A4 activity, but also
      cell damage and repressed hepatic functionality in cluster-neighbouring regions.
      The levels of ammonia elimination, apolipoprotein A-1 production, and
      transcription of CYP3A4, CYP2B6 and albumin reached those of primary hepatocytes
      in either the + or -DMSO cultures. Preconditioning with CG increased conversion
      of (15)NH(4)Cl into (15)N-urea 4-fold only in -DMSO cultures. Hence, HepaRG cells
      show high metabolic and synthetic functionality in the absence of DMSO, however,
      their drug metabolism is only high in the presence of DMSO. An unparalleled broad
      hepatic functionality, suitable for bioartificial liver application, can be
      accomplished by combining CG treated -DMSO cultures with +DMSO cultures.

PMID- 21726662
TI  - Comparison of the Kato-Katz and FLOTAC techniques for the diagnosis of soil
      transmitted helminth infections.
AB  - Decisions on individual or community treatment and evaluation of chemotherapy
      based control programs depend on parasitological diagnostic techniques. The aim
      of this study was to compare the accuracy of a single Kato-Katz thick smear and a
      single FLOTAC for the determination of the prevalence and intensity of soil
      transmitted helminth infections. A total of 271 faecal specimens were collected
      from schoolchildren in Ethiopia, and microscopically examined using the Kato-Katz
      method (41.7 mg stool per slide) and the FLOTAC technique. The combined results
      from the Kato-Katz and FLOTAC methods were used as diagnostic 'gold' standard for
      reference in the analysis. Agreement between the two methods showed kappa values
      of 0.74, 0.73 and 0.28 for Ascaris lumbricoides, Trichuris trichiura and
      hookworm, respectively. A single FLOTAC revealed significantly more infections
      than a single Kato-Katz for each of the three soil-transmitted helminths
      (p<0.01). The sensitivities of a single Kato-Katz for diagnosis of T. trichiura,
      A. lumbricoides and hookworm infections were 76.6%, 67.8% and 19.6%,
      respectively, while the sensitivity of FLOTAC was 100% for all the three soil
      transmitted helminth species. A single Kato-Katz yielded considerably higher mean
      faecal egg counts (FECs) (729.1, 145.2 and 60.7 eggs per gram of stool (EPG) for
      A. lumbricoides, T. trichiura and hookworm, respectively) compared with a single
      FLOTAC (142.5, 54.5 and 14.6 EPG, respectively) (p<0.05). Our study confirms that
      a single FLOTAC is more sensitive than a single Kato-Katz for the diagnosis of
      soil-transmitted helminth infections, but results in lower FECs. Further
      standardization and validation are still required in different epidemiological
      settings with varying levels of intensity of infections before recommending
      FLOTAC for large-scale community diagnosis.

PMID- 21726663
TI  - Genomic changes in gliomas detected using single nucleotide polymorphism array in
      formalin-fixed, paraffin-embedded tissue: superior results compared with
      microsatellite analysis.
AB  - Deletion or loss of heterozygosity (LOH) in chromosomes 1p and 19q in
      oligodendrogliomas (ODGs) have diagnostic, prognostic, and therapeutic
      implications. Current clinical assays are limited because the probes or primers
      interrogate only limited genomic segments. We investigated the use of single
      nucleotide polymorphism (SNP) arrays for identifying genomic changes in gliomas
      from FFPE tissues. DNA was extracted from FFPE tissues of 30 brain tumor cases
      (15 ODGs and 15 non-ODGs) and assayed on the Illumina array with 300,000 markers.
      SNP results were compared with standard short tandem repeat (STR) assays of
      chromosomes 1p and 19q. Fifteen ODGs had LOH by STR and deletion by array on both
      1p and 19q. Ten non-ODGs had no evidence of LOH on 1p and 19q by STR, seven of
      which had no abnormalities for these chromosomes; three had partial deletions by
      SNP array. Five non-ODG cases had partial LOH or deletion by both assays. No
      major discordance was found between SNP array and STR results. Advantages of SNP
      arrays include no need for an accompanying normal sample, the ability to find
      small segmental deletions, the potential to distinguish between deletions and
      copy neutral LOH, and whole-genome screening to allow discovery of new,
      significant loci. Assessment of genomic changes in routine glioma specimens using
      SNP arrays is feasible and has great potential as an accurate clinical diagnostic
      test.

PMID- 21726664
TI  - Multiplex mutation screening by mass spectrometry evaluation of 820 cases from a
      personalized cancer medicine registry.
AB  - There is an immediate and critical need for a rapid, broad-based genotyping
      method that can evaluate multiple mutations simultaneously in clinical cancer
      specimens and identify patients most likely to benefit from targeted agents now
      in use or in late-stage clinical development. We have implemented a prospective
      genotyping approach to characterize the frequency and spectrum of mutations
      amenable to drug targeting present in urothelial, colorectal, endometrioid, and
      thyroid carcinomas and in melanoma. Cancer patients were enrolled in a
      Personalized Cancer Medicine Registry that houses both clinical information and
      genotyping data, and mutation screening was performed using a multiplexed assay
      panel with mass spectrometry-based analysis to detect 390 mutations across 30
      cancer genes. Formalin fixed, paraffin-embedded specimens were evaluated from 820
      Registry patients. The genes most frequently mutated across multiple cancer types
      were BRAF, PIK3CA, KRAS, and NRAS. Less common mutations were also observed in
      AKT1, CTNNB1, FGFR2, FGFR3, GNAQ, HRAS, and MAP2K1. Notably, 48 of 77 PIK3CA
      mutant cases (62%) harbored at least one additional mutation in another gene,
      most often KRAS. Among melanomas, only 54 of 73 BRAF mutations (74%) were the
      V600E substitution. These findings demonstrate the diversity and complexity of
      mutations in druggable targets among the different cancer types and underscore
      the need for a broad-spectrum, prospective genotyping approach to personalized
      cancer medicine.

PMID- 21726665
TI  - Three new loci for determining x chromosome inactivation patterns.
AB  - The analysis of X chromosome inactivation (XCI) patterns is a widely used
      diagnostic tool in clinical practice when investigating X-linked diseases. The
      most commonly used assay to determine XCI patterns takes advantage of a locus
      within the androgen receptor (AR) gene. This PCR-based assay relies on two
      differentially methylated restriction enzyme sites (HpaII) and a polymorphic
      repeat located within this locus. Although highly informative, this locus is not
      always sufficient to evaluate the X-inactivation status in X-linked disorders. We
      have identified three new loci that can be used to determine XCI patterns in a
      methylation-sensitive PCR-based assay. All three loci contain polymorphic repeats
      and a methylation-sensitive restriction enzyme (HpaII) site, methylation of which
      was shown to correlate with XCI. DNA from 60 females was used to estimate the
      heterozygosity of these new loci. The reliability of the loci was validated by
      showing a high correlation between the results obtained by employing the new loci
      and the AR locus using DNA from 15 females who were informative for all four
      loci. Altogether, we show that these loci can be applied easily in molecular
      diagnostic laboratories, either as a supplement or as an alternative to the
      existing AR assay.

PMID- 21726666
TI  - A locked nucleic acid clamp-mediated PCR assay for detection of a p53 codon 249
      hotspot mutation in urine.
AB  - Hepatocellular carcinoma (HCC) has a 5-year survival rate of <10% because it is
      difficult to diagnose early. Mutations in the TP53 gene are associated with
      approximately 50% of human cancers. A hotspot mutation, a G:C to T:A transversion
      at codon 249 (249T), may be a potential DNA marker for HCC screening because of
      its exclusive presence in HCC and its detection in the circulation of some
      patients with HCC. A locked nucleic acid clamp-mediated PCR assay, followed by
      melting curve analysis (using the SimpleProbe), was developed to detect the TP53
      249T mutation. In this assay, the locked nucleic acid clamp suppressed 10(7)
      copies of wild-type templates and permitted detection of 249T-mutated template,
      with a sensitivity of 0.1% (1:1000) of the mutant/wild-type ratio, assessed by a
      reconstituted standard within 2 hours. With an amplicon size of 41 bp, it detects
      target DNA sequences in short fragmented DNA templates. The detected mutations
      were validated by DNA sequencing analysis. We then tested DNA isolated from urine
      samples of patients with HCC for p53 mutations and identified positive TP53
      mutations in 9 of 17 samples. The possibility of using this novel TP53 249T assay
      to develop a urine or blood test for HCC screening is discussed.

PMID- 21726667
TI  - Effects of cadmium on carbohydrate and protein metabolisms in the freshwater crab
      Sinopotamon yangtsekiense.
AB  - The physiological impact of Cd(2+) on Sinopotamon yangtsekiense was evaluated
      through changes of selected parameters considered as key elements of carbohydrate
      and protein metabolisms. Crab were exposed to 0.725, 1.45, 2.9mg.L(-1) Cd(2+) for
      7, 14 and 21 days. A time- and/or concentration- dependent decrease in muscle
      glycogen and increase in LDH activity suggested that glycolysis was accelerated
      during the treatments. Increased protease activity, lowering of FAA and the
      initially increased and subsequently decreased aminotransferase activities
      suggest an enhanced protein mobilization during early Cd(2+) exposure followed by
      a metabolic impairment during late exposure. Decreased hemolymph glucose level
      was observed in the crabs treated with 2.9mg.L(-1) Cd(2+) for 21d, suggesting an
      impaired gluconeogenesis. Ammonia level barely changed during the 14d Cd(2+)
      exposure most likely due to the increased urea and glutamine production; After
      1.45 and 2.9mg.L(-1) Cd(2+) treatment for 21d, ammonia was observed increased
      followed by an exclusive increase in glutamine. Taken together, our results
      indicate that carbohydrate and protein are mobilized to a varying degree as a
      compensatory metabolism to response to the energy stress during acute Cd(2+)
      exposure. As the time lapsed, some symptoms on metabolism obstacle reflect the
      toxic effect of sublethal Cd(2+).

PMID- 21726668
TI  - The challenges of implementing pathogen control strategies for fishes used in
      biomedical research.
AB  - Over the past several decades, a number of fish species, including the zebrafish,
      medaka, and platyfish/swordtail, have become important models for human health
      and disease. Despite the increasing prevalence of these and other fish species in
      research, methods for health maintenance and the management of diseases in
      laboratory populations of these animals are underdeveloped. There is a growing
      realization that this trend must change, especially as the use of these species
      expands beyond developmental biology and more towards experimental applications
      where the presence of underlying disease may affect the physiology animals used
      in experiments and potentially compromise research results. Therefore, there is a
      critical need to develop, improve, and implement strategies for managing health
      and disease in aquatic research facilities. The purpose of this review is to
      report the proceedings of a workshop entitled "Animal Health and Disease
      Management in Research Animals" that was recently held at the 5th Aquatic Animal
      Models for Human Disease in September 2010 at Corvallis, Oregon to discuss the
      challenges involved with moving the field forward on this front.

PMID- 21726669
TI  - Cloning and spatiotemporal expression of RIC-8 in Xenopus embryogenesis.
AB  - RIC-8 is a highly conserved protein that promotes G protein signaling as it acts
      as a Guanine nucleotide Exchanging Factor (GEF) over a subset of Galpha subunits.
      In invertebrates, RIC-8 plays crucial roles in synaptic transmission as well as
      in asymmetric cell division. As a first step to address further studies on RIC-8
      function in vertebrates, here we have cloned a ric-8 gene from Xenopus tropicalis
      (xtric-8) and determined its spatiotemporal expression pattern throughout
      embryogenesis. The xtric-8 transcript is expressed maternally and zygotically
      and, as development proceeds, it shows a dynamic expression pattern. At early
      developmental stages, xtric-8 is expressed in the animal hemisphere, whereas its
      expression is later restricted to neural tissues, such as the neural tube and the
      brain, as well as in the eye and neural crest-derived structures, including those
      of the craniofacial region. Together, our findings suggest that RIC-8 functions
      are related to the development of the nervous system.

PMID- 21726670
TI  - Toll-like receptor 4 gene polymorphism and giant cell arteritis susceptibility: a
      cumulative meta-analysis.
AB  - OBJECTIVE: Toll-like receptor (TLR) 4 (+896 A/G) gene polymorphism has been
      reported to be associated with susceptibility to giant cell arteritis (GCA) with
      inconsistent results. To provide a more definitive conclusion, a cumulative meta
      analysis of the association of TLR4 (+896 A/G) polymorphism with GCA
      susceptibility combining previous studies was performed. METHODS: The cumulative
      meta-analysis included 3 case-control studies which provided a total of 437
      patients and 1023 controls. Meta-analysis was conducted by fitting random effects
      models and checked for heterogeneity and publication bias. Combined odds ratio
      (OR) and associated 95% confidence intervals (CI) were obtained by using a
      DerSimonian and Laird random effects model. RESULTS: Three studies, all from a
      South European ancestry, were identified through a literature search and included
      in this meta-analysis. The cumulative meta-analysis showed that the pooled random
      effects OR was non significant (OR: 1.46, 95% CI: 0.95-2.25; p = 0.082). There is
      some evidence suggestive of moderate-high heterogeneity between the three
      studies, I2 34.2% (95% CI: 0-55.2). CONCLUSION: This cumulative meta-analysis
      does not demonstrate an association of TLR4 (+896 A/G) gene polymorphism with
      susceptibility to GCA. Further studies using larger samples and in populations
      from different geographic origins are needed to determine the exact role of TLR4
      gene polymorphisms in GCA.

PMID- 21726671
TI  - Inhibition of pre-B cell colony-enhancing factor attenuates inflammation and
      apoptosis induced by pandemic H1N1 2009 in lung endothelium.
AB  - The recent pandemic influenza A (H1N1 2009) virus infection has caused acute lung
      injury in susceptible population resulting in high mortality in ICU patients. In
      this report, we observed the effect of pre-B cell colony-enhancing factor (PBEF)
      on the inflammation and apoptosis in H1N1-infected human pulmonary microvascular
      endothelial cells (HPMECs). We constructed an in vitro HPMEC monolayer model. The
      results showed that H1N1 2009 induced the increased expression of inflammatory
      cytokines (IL-6/IL-8/TNF-alpha/IP-10) and apoptosis factors (FasL/TRAIL) in
      infected HPMECs. However, PBEF silencing with siRNA inhibited the expression of
      some inflammatory cytokines and decreased the apoptosis mediated by FasL. We
      conclude that PBEF might be partially responsible for the localized inflammatory
      response to H1N1 2009 in the lung microvascular endothelium and the H1N1-induced
      endothelial cell apoptosis probably through the FasL-mediated pathway.

PMID- 21726672
TI  - The transition of the European Proteomics Association into the future.
AB  - The following report provides an overview of the discussions and outcome of the
      EuPA General Council meeting that took place in Estoril 20-21 October 2010.
      During the annual meeting future policy and action plans in a variety of areas
      are decided. Several important points were decided upon during this meeting
      including the expansion of the EuPA Executive Committee by introducing a new EuPA
      committee - EuPA Developments - that will initially spearhead activities in
      standardisation, imaging ms and biobanking. The EuPA General Council also invited
      Russia as its 17th member. More details about these and additional activities are
      presented in the article.

PMID- 21726673
TI  - The use of a novel quantitation strategy based on Reductive Isotopic Di
      Ethylation (RIDE) to evaluate the effect of glufosinate on the unicellular algae
      Ostreococcus tauri.
AB  - We report a novel stable-isotope labeling strategy for quantitative proteomics
      analysis. The method consists of labeling N-termini and lysine epsilon-amino
      groups through reductive amination using acetaldehyde. This allows isotope
      labeling using pairs of either 2H/1H or 13C/12C without mass spectrum overlap.
      Our labeling procedure, which is significantly different than that developed for
      dimethylation, can be completed with little trace of partial ethylation; non
      labeled peptides represent less than 0.05% of all peptides. Co-elution of both
      isotopic 13C/12C peptide pairs was observed in all cases, simplifying data
      analysis, which can be performed using standard commercial software such as
      Mascot Distiller. A 13C/12C labeled mix in a 1:1 ratio from a complex extract
      digest of the unicellular algae Ostreococcus tauri, showed a relative standard
      deviation of less than 14%. This quantitative method was used to characterize O.
      tauri in the presence of glufosinate, an herbicide which inhibits glutamine
      synthetase. Blocking glutamine synthetase significantly reduced the expression of
      several enzymes and transporters involved in nitrogen assimilation and the
      expression of a number of proteins involved in various stresses including
      oxidative damage response were up-regulated.

PMID- 21726675
TI  - Valproic acid synergistically enhances the cytotoxicity of gossypol in DU145
      prostate cancer cells: an iTRTAQ-based quantitative proteomic analysis.
AB  - Gossypol (GOS), a BH3 mimetic, has been investigated as a sensitizing co-therapy
      to radiation and chemotherapy in treatment of metastatic prostate cancer. In this
      study, we found that valproic acid (VPA), a histone deacetylase inhibitor
      (HDACI), counteracted the suppressive effect of GOS on histone H3 acetylation and
      enhanced the cytotoxicity of GOS to DU145 prostate cancer cells. Significant
      synergistic effects were observed in combined GOS and VPA treatment, culminating
      in more DNA damage and cell death. The iTRAQ-based quantitative proteomic
      analysis revealed differential proteomic profiles in cells treated with VPA, GOS
      or their combination. In GOS-treated cells, oxidative phosphorylation-related
      proteins were depressed and endoplasmic reticulum stress markers were
      upregulated. In the presence of VPA, the GOS-induced mitochondrial stress was
      further enhanced since glycolysis- and hypoxia-associated proteins were
      upregulated, suggesting a disruption of energy metabolism in these cells.
      Furthermore, the DNA damage repair ability of cells co-treated with GOS and VPA
      was also decreased, as evidenced by the downregulation of DNA damage repair
      proteins and the enhancement of DNA fragmentation and cell death. These findings
      suggest that GOS in combination with an HDACI has the potential to increase its
      clinical efficacy in the treatment of prostate cancer.

PMID- 21726674
TI  - Proteomic identification of specifically carbonylated brain proteins in
      APP(NLh)/APP(NLh) * PS-1(P264L)/PS-1(P264L) human double mutant knock-in mice
      model of Alzheimer disease as a function of age.
AB  - Alzheimer disease (AD) is the most common type of dementia and is characterized
      pathologically by the presence of neurofibrillary tangles (NFTs), senile plaques
      (SPs), and loss of synapses. The main component of SP is amyloid-beta peptide
      (Abeta), a 39 to 43 amino acid peptide, generated by the proteolytic cleavage of
      amyloid precursor protein (APP) by the action of beta- and gamma-secretases. The
      presenilins (PS) are components of the gamma-secretase, which contains the
      protease active center. Mutations in PS enhance the production of the Abeta42
      peptide. To date, more than 160 mutations in PS1 have been identified. Many PS
      mutations increase the production of the beta-secretase-mediated C-terminal (CT)
      99 amino acid-long fragment (CT99), which is subsequently cleaved by gamma
      secretase to yield Abeta peptides. Abeta has been proposed to induce oxidative
      stress and neurotoxicity. Previous studies from our laboratory and others showed
      an age-dependent increase in oxidative stress markers, loss of lipid asymmetry,
      and Abeta production and amyloid deposition in the brain of APP/PS1 mice. In the
      present study, we used APP (NLh)/APP(NLh) * PS-1(P246L)/PS-1(P246L) human double
      mutant knock-in APP/PS-1 mice to identify specific targets of brain protein
      carbonylation in an age-dependent manner. We found a number of proteins that are
      oxidatively modified in APP/PS1 mice compared to age-matched controls. The
      relevance of the identified proteins to the progression and pathogenesis of AD is
      discussed.

PMID- 21726676
TI  - Parathyroid hormone receptor signaling in osteocytes increases the expression of
      fibroblast growth factor-23 in vitro and in vivo.
AB  - Mice with constitutive activation of parathyroid hormone (PTH) receptor signaling
      in osteocytes (DMP1-caPTHR1 transgenic mice) exhibit increased bone mass and
      remodeling, two of the recognized skeletal actions of PTH. Moreover, similar to
      PTH administration, DMP1-caPTHR1 mice exhibit decreased expression of the
      osteocyte-derived Wnt antagonist Sost/sclerostin. We now report that PTH receptor
      activation also regulates in vivo and in vitro the expression of fibroblast
      growth factor 23 (FGF23), an osteocyte product involved in inorganic phosphate
      (Pi) homeostasis and bone mineralization. Whole bones and osteocytes, but not
      osteoblasts, from DMP1-caPTHR1 mice exhibit elevated FGF23 expression, which is
      corrected in double transgenic mice overexpressing Sost in osteocytes. PTH, PTH
      related protein (PTHrP), or a cAMP stable analog, increase FGF23 transcripts in a
      time- and dose-dependent manner in osteocyte-containing calvarial cell cultures.
      Circulating FGF23 is also elevated in DMP1-caPTHR1 mice; however, plasma Pi or
      renal Pi reabsorption is not altered. Furthermore, the FGF23 receptor complex
      comprising FGFR1 and KLOTHO is expressed in osteoblastic cells; and FGFR1,
      GALNT3, as well as downstream targets of FGF23 signaling, are increased in
      osteocytes but not in osteoblasts from DMP1-caPTHR1 mice. Thus, PTH receptor
      signaling has the potential to modulate the endocrine and auto/paracrine
      functions of osteocytes by regulating FGF23 through cAMP- and Wnt-dependent
      mechanisms.

PMID- 21726677
TI  - Loss of transcription factor early growth response gene 1 results in impaired
      endochondral bone repair.
AB  - Transcription factors that play a role in ossification during development are
      expected to participate in postnatal fracture repair since the endochondral bone
      formation that occurs in embryos is recapitulated during fracture repair.
      However, inherent differences exist between bone development and fracture repair,
      including a sudden disruption of tissue integrity followed by an inflammatory
      response. This raises the possibility that repair-specific transcription factors
      participate in bone healing. Here, we assessed the consequence of loss of early
      growth response gene 1 (EGR-1) on endochondral bone healing because this
      transcription factor has been shown to modulate repair in vascularized tissues.
      Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice.
      Differences in tissue morphology and composition between these two animal groups
      were followed over 28 post fracture days (PFDs). In wt mice, bone healing
      occurred in healing phases characteristic of endochondral bone repair. A similar
      healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations.
      A persistent accumulation of fibrin between the disconnected bones was observed
      on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14
      callus was abnormally enlarged and showed increased deposition of mineralized
      tissue. Cartilage ossification in the callus was associated with hyper
      vascularity and -proliferation. Moreover, cell deposits located in proximity to
      the callus within skeletal muscle were detected on PFD14. Despite these
      impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is
      not essential for healing. Together, this study provides genetic evidence that
      EGR-1 is a pleiotropic regulator of endochondral fracture repair.

PMID- 21726679
TI  - Technological advances in dentistry and oral surgery. Preface.

PMID- 21726678
TI  - Effects of 50 Hz sinusoidal electromagnetic fields of different intensities on
      proliferation, differentiation and mineralization potentials of rat osteoblasts.
AB  - Electromagnetic fields (EMFs) have been used clinically to slow down osteoporosis
      and promote fracture healing for many years. However, the underlying action
      mechanisms and optimal parameters of the EMF applications are unclear. In this
      study, we investigated the effects of treatment for different durations with 50
      Hz sinusoidal electromagnetic fields (SEMFs) at different intensities on
      proliferation, differentiation and mineralization potentials of rat osteoblasts.
      Osteoblasts isolated from neonatal rats were treated with SEMFs (50 Hz at 0.9 mT
      4.8 mT, 0.3 mT interval, 30 min/day up to 15 days). Compared to untreated
      control, SEMFs inhibited osteoblast proliferation (after 3 days' treatment) but
      increased alkaline phosphatase (ALP) activity (after treatment for 9 days) from
      0.9 mT to 1.8 mT, declined from 1.8 mT until 3.0 mT, and then increased again
      from 3.0 mT to 3.6 mT and decreased once again from 3.6 mT to 4.8 mT. Numbers of
      colonies stained positive for ALP after 8 days and mineralized nodules stained by
      Alizarin red after 10 days showed the same bimodal tendency as with the ALP
      activity, with two peaks at 1.8 mT and 3.6 mT. SEMFs also bimodally increased
      Runx-2, Col1alpha2 and Bmp-2 mRNA expression levels in osteoblasts at 12, 24 and
      96 h after exposure. The results indicated that while exposure to 50 Hz SEMFs
      inhibits the osteoblast proliferation, it significantly promotes differentiation
      and mineralization potentials of osteoblasts in an intensity-dependent manner
      with peak activity at 1.8 mT and 3.6 mT.

PMID- 21726680
TI  - Advances in pediatric dentistry.
AB  - This article addresses advances in 4 key areas related to pediatric dentistry:
      (1) caries detection tools, (2) early interventions to arrest disease
      progression, (3) caries-risk assessment tools, and (4) trends in pediatric
      procedures and dental materials.

PMID- 21726681
TI  - Hemostatic agents.
AB  - Hemostasis is an integral and very important aspect of surgical practice. As a
      rule, most bleeding from dental surgery can be controlled by pressure. When the
      application of pressure does not yield satisfactory results, or where more
      effective hemostasis is required, hemostatic agents are used. These agents act to
      stop bleeding either mechanically or by augmenting the coagulation cascade. Some
      of the newer agents that are available to the dental profession have been
      presented.

PMID- 21726682
TI  - Technological advances in caries diagnosis.
AB  - Understanding the nature of the caries lesion, disease activity, and the
      patient's caries risk are all used in determining the nature of dental care to be
      delivered. An examination should include a health and social history and clinical
      examination using appropriate technologies. This allows proper assessment and
      suggests a logical management intervention. Minimally invasive dentistry is a
      concept based on an assessment of a patient's caries risk and the application of
      the current therapies to prevent, control, and treat the disease. The history of
      the dental examination and the variety of current technologies are discussed.

PMID- 21726683
TI  - Advanced techniques in bone grafting procedures.
AB  - Technological advancement in bone grafting procedures using purified proteins or
      stem cells to induce osteogenesis is a significant contribution to patient care.
      Patients who would otherwise not have been suitable candidates for major
      autologous bone grafting procedures can continue to benefit from implant
      reconstruction, with a less debilitating bone reconstructive procedure.

PMID- 21726684
TI  - Technologic advances in endodontics.
AB  - This article addresses technologic advances in endodontics pertaining to new and
      emerging technology. Cone-beam computed tomography and optical occurrence
      tomography are 2 new imaging technologies that can assist the practitioner in the
      diagnosis of pulpal disease. The self-adjusting file and the Apexum device can be
      used for instrumentation and bulk debridement of an apical lesion, respectively.
      Neodymium:yttrium-aluminum-garnet laser, erbium:chromium:yttrium-scandium-gallium
      garnet laser, EndoActivator, EndoVac, and light-activated disinfection may assist
      the practitioner in cleaning the root canal system. Computed tomography-guided
      surgery shows promise in making endodontic surgery easier, as does mineral
      trioxide aggregate cement for regenerative endodontic procedures.

PMID- 21726685
TI  - Advances in local anesthesia in dentistry.
AB  - Local pain management is the most critical aspect of patient care in dentistry.
      The improvements in agents and techniques for local anesthesia are probably the
      most significant advances that have occurred in dental science. This article
      provides an update on the most recently introduced local anesthetic agents along
      with new technologies used to deliver local anesthetics. Safety devices are also
      discussed, along with an innovative method for reducing the annoying numbness of
      the lip and tongue following local anesthesia.

PMID- 21726686
TI  - Technological advances in extraction techniques and outpatient oral surgery.
AB  - There have been several exciting technological advances in extraction techniques
      and outpatient oral surgery within the last decade. A variety of new instruments
      and techniques are revolutionizing the fields of oral and maxillofacial surgery
      and dentistry. This article reviews the newer innovations in dentistry including
      the powered periotome, piezosurgery, the Physics Forceps, laser therapy,
      orthodontic techniques, and use of polyurethane foam.

PMID- 21726687
TI  - Cone beam computed tomography-assisted treatment planning concepts.
AB  - Computed tomography (CT) and cone-beam CT (CBCT) technology allows three
      dimensional evaluation of each patient's individual anatomy. This article
      highlights the presurgical planning phase of dental implant procedures that
      benefit from lower dose CBCT technology so that educated treatment decisions can
      be accurately determined. Clinicians should gain an understanding of how each
      view can be individually significant, with unique levels of detail helping to
      provide a comprehensive overview of the patient's anatomic presentation. This
      article outlines the benefits of using CBCT technology for dental implant
      applications for increased accuracy and avoidance of potential surgical and
      restorative complications.

PMID- 21726688
TI  - Oral cancer detection.
AB  - There are approximately 21,000 new cases of oral cancer every year. Although the
      oral cavity is relatively accessible to examination, malignant processes tend to
      present late with poor prognosis. To improve tumor outcome, early detection and
      treatment is essential. This article reviews the realms of oral cancer and its
      causes, as well as early detection methods and screening technologies that may be
      used. Currently available screening tools may help in visualizing an existing
      lesion or its borders, but they add little in discriminating between a
      premalignant, malignant, or inflammatory process.

PMID- 21726689
TI  - Office computer systems for the dental office.
AB  - The role of computers in dental practice has dramatically changed over the past
      30 years. We have witnessed the progression from administrative roles to complete
      integration leading to chartless offices. As the dental community gradually
      adopts this contemporary development, the move to electronic health records is
      imminent because of upcoming changes in the health care system. The past,
      present, and future of dental office computer systems is explored in this
      article. An understanding of the benefits and current challenges of contemporary
      dental practice software is also reviewed.

PMID- 21726690
TI  - The use of CAD/CAM in dentistry.
AB  - Computer-aided design (CAD) and computer-aided manufacturing (CAM) have become an
      increasingly popular part of dentistry over the past 25 years. The technology,
      which is used in both the dental laboratory and the dental office, can be applied
      to inlays, onlays, veneers, crowns, fixed partial dentures, implant abutments,
      and even full-mouth reconstruction. This article discusses the history of CAD/CAM
      in dentistry and gives an overview of how it works. It also provides information
      on the advantages and disadvantages, describes the main products available,
      discusses how to incorporate the new technology into your practice, and addresses
      future applications.

PMID- 21726691
TI  - Technological advances in nontraditional orthodontics.
AB  - New technological advances have helped the orthodontic profession progress in
      traditional and surgical methods of treatment. The profession has seen
      transitions from traditional braces to self-ligating brackets, lingual braces,
      removable aligners, and more advanced technology, which have helped to address
      concerns that include but are not limited to better diagnostics, anchorage
      control, length of treatment, and esthetics. An increase in the number of adult
      patients seeking orthodontic treatment and the need for a timely efficient care
      will continue to drive technology and the use of cone beam computed tomography,
      miniscrews, piezocision, distraction osteogenesis, and bioengineering.

PMID- 21726692
TI  - Lasers and radiofrequency devices in dentistry.
AB  - Advances in technology are changing the ways that patients experience dental
      treatment. Technology helps to decrease treatment time and makes the treatment
      more comfortable for the patient. One technological advance is the use of lasers
      in dentistry. Lasers are providing more efficient, more comfortable, and more
      predictable outcomes for patients. Lasers are used in all aspects of dentistry,
      including operative, periodontal, endodontic, orthodontic, and oral and
      maxillofacial surgery. Lasers are used for soft and hard tissue procedures in the
      treatment of pathologic conditions and for esthetic procedures. This article
      discusses how lasers work and their application in the various specialties within
      dentistry.

PMID- 21726693
TI  - Treatment of dentin hypersensitivity.
AB  - Dentinal hypersensitivity is exemplified by brief, sharp, well-localized pain in
      response to thermal, evaporative, tactile, osmotic, or chemical stimuli that
      cannot be ascribed to any other form of dental defect or pathology. Pulpal pain
      is usually more prolonged, dull, aching, and poorly localized and lasts longer
      than the applied stimulus. Up to 30% of adults have dentinal hypersensitivity at
      some time. Current techniques for treatment may be only transient in nature and
      results are not always predictable. Two methods of treatment of dentin
      hypersensitivity are tubular occlusion and blockage of nerve activity. A
      differential diagnosis needs to be accomplished before any treatment.

PMID- 21726694
TI  - Current treatments and advances in pain and anxiety management.
AB  - In light of preoperative and postoperative mortality and morbidity, continued
      advancement in pain and anxiety management would benefit millions. Although
      significant strides have been made in the past few decades, it is imperative that
      research and development continue. This article discusses types of pain and
      anxiety, the relationship between pain and anxiety, the physiology of pain and
      anxiety, and current trends in pain and anxiety management.

PMID- 21726695
TI  - Advances in dental materials.
AB  - The use of materials to rehabilitate tooth structures is constantly changing.
      Over the past decade, newer material processing techniques and technologies have
      significantly improved the dependability and predictability of dental material
      for clinicians. The greatest obstacle, however, is in choosing the right
      combination for continued success. Finding predictable approaches for successful
      restorative procedures has been the goal of clinical and material scientists.
      This article provides a broad perspective on the advances made in various classes
      of dental restorative materials in terms of their functionality with respect to
      pit and fissure sealants, glass ionomers, and dental composites.

PMID- 21726696
TI  - Technological updates in dental photography.
AB  - Digital photography is a constantly evolving medium that can be used in dentistry
      for a number of applications including documentation and patient education. In
      the past 5 years, it has become standard professional practice for photographers
      to shoot in raw format, organize and edit in Adobe Photoshop Lightroom, and
      archive files using portable hard drives and off-site storage. Concurrently,
      cameras have increased resolution, improved antidust technology, and added
      versatile flash accessories for macro imaging. Adopting professional photographic
      practices and taking advantage of technological developments in a dental practice
      can be an invaluable tool in education and documentation.

PMID- 21726697
TI  - Technological advances in minimally invasive TMJ surgery.
AB  - The technologic advances in temporomandibular joint arthroscopy and
      arthrocentesis have given oral surgeons a treatment for patients who have not
      responded to conservative and pharmacologic treatment without the surgical risks
      and long-term recovery of open joint surgery.

PMID- 21726698
TI  - Letter from the editor: lung cancer screening: what do you know?

PMID- 21726699
TI  - Letter from the guest editor: lung cancer.

PMID- 21726700
TI  - Case of the season: primary pulmonary collision tumor consisting of carcinoid and
      high-grade spindle-cell sarcoma.

PMID- 21726701
TI  - Epidemiology of lung cancer.

PMID- 21726702
TI  - Classification of lung cancer.

PMID- 21726704
TI  - Imaging characteristics of lung cancer.

PMID- 21726703
TI  - Lung cancer staging: an overview of the new staging system and implications for
      radiographic clinical staging.

PMID- 21726705
TI  - 18F-2-Deoxy-d-Glucose positron emission tomography-computed tomography in lung
      cancer.

PMID- 21726706
TI  - Radiofrequency ablation: treatment of primary lung cancer.

PMID- 21726707
TI  - Lung cancer screening: achieving a reduction in mortality.

PMID- 21726708
TI  - Recent trends in application of multivariate curve resolution approaches for
      improving gas chromatography-mass spectrometry analysis of essential oils.
AB  - Essential oils (EOs) are valuable natural products that are popular nowadays in
      the world due to their effects on the health conditions of human beings and their
      role in preventing and curing diseases. In addition, EOs have a broad range of
      applications in foods, perfumes, cosmetics and human nutrition. Among different
      techniques for analysis of EOs, gas chromatography-mass spectrometry (GC-MS) is
      the most important one in recent years. However, there are some fundamental
      problems in GC-MS analysis including baseline drift, spectral background, noise,
      low S/N (signal to noise) ratio, changes in the peak shapes and co-elution.
      Multivariate curve resolution (MCR) approaches cope with ongoing challenges and
      are able to handle these problems. This review focuses on the application of MCR
      techniques for improving GC-MS analysis of EOs published between January 2000 and
      December 2010. In the first part, the importance of EOs in human life and their
      relevance in analytical chemistry is discussed. In the second part, an insight
      into some basics needed to understand prospects and limitations of the MCR
      techniques are given. In the third part, the significance of the combination of
      the MCR approaches with GC-MS analysis of EOs is highlighted. Furthermore, the
      commonly used algorithms for preprocessing, chemical rank determination, local
      rank analysis and multivariate resolution in the field of EOs analysis are
      reviewed.

PMID- 21726709
TI  - Very low optical absorptions and analyte concentrations in water measured by
      Optimized Thermal Lens Spectrometry.
AB  - Thermal Lens Spectrometry has traditionally been carried out in the single-beam
      and the mode-mismatched dual-beam configurations. Recently, a much more sensitive
      dual-beam TL setup was developed, where the probe beam is expanded and
      collimated. This feature optimizes Thermal Lens (TL) signal and allows the use of
      thicker samples, further improving the sensitivity. In this paper, we have made
      comparisons between the conventional and optimized TL configurations, and
      presented applications such as measurements of very low absorptions and
      concentrations in water and Cr(III) aqueous solution in the UV-vis range. For
      pure water we found linear absorption coefficients as low as the Raman scattering
      one due to the stretching vibrational modes of OH group. The detection limit was
      estimated 1 * 10(-6)cm(-1) with a 180-mW excitation power using a 100-mm cell
      length. This sensitivity is very high, considering that water has a photothermal
      enhancement factor ~ 33 times smaller than CCl(4), for example. For Cr(III)
      species in aqueous solution, the limit of detection (LOD) was estimated in ~ 40
      ng mL(-1) at 514 nm, or ~ 10 ng mL(-1) at 405 nm, which is ~ 30 times smaller
      than the LOD achieved with conventional transmission techniques. The more recent
      TL configuration is very attractive to obtain absorption spectra, since the
      result does not depend critically on the beam parameters, unlike the other
      configurations. The main drawbacks of this optimized TL configuration are the
      longer acquisition time and the need for larger samples.

PMID- 21726710
TI  - Development and validation of an assay method for the determination of
      trifluoroacetic acid in a cyclosporin-like drug.
AB  - An improved method for the assay of trifluoroacetic acid (TFA) in a cyclosporin
      like drug substance is presented, based on ion chromatography with suppressed
      conductivity detection. Column fouling by the drug molecule is avoided by use of
      a sample preparation method in which the drug substance is precipitated at
      alkaline pH whilst the TFA remains in solution. The new method requires a smaller
      sample mass than a previous method based on headspace-GC-FID whilst achieving an
      improvement in sensitivity. During validation, the method's performance was found
      to be consistent with usual acceptance criteria, and the method was found to be
      robust in routine use.

PMID- 21726711
TI  - Optimization of a Dynamic Headspace-Thermal Desorption-Gas Chromatography/Mass
      Spectrometry procedure for the determination of furfurals in vinegars.
AB  - The use of a Dynamic Headspace System (DHS) device combined with a Thermal
      Desorption Unit (TDU) interfaced to a Gas Chromatography/Mass Spectrometry
      (GC/MS) system is proposed for the determination of furfurals in oenological
      products. An experimental design protocol has been employed for the optimization
      of the instrumental settings concerning DHS and TDU extraction and desorption
      steps. It has been possible to individuate the following optimized conditions:
      incubation temperature 40 degrees C, purge volume 800 mL, dry volume 1500 mL, TDU
      hold time 5 min and incubation time 10 min. The performance of two different SPE
      sorbents, namely Tenax TA and Tenax GR used for the furfurals trapping, was
      investigated too. The developed DHS sampling procedure showed good
      reproducibility values with a RSD% lower than 10% for all the monitored species.
      The optimized experimental settings have been used to determine furfurals in
      several vinegar samples obtained by traditional procedure starting from cooked
      grape musts, i.e. in Aceto Balsamico Tradizionale di Modena (ABTM). In fact, the
      control of these species is extremely important for quality and safety issues.

PMID- 21726712
TI  - Selective determination of homocysteine levels in human plasma using a silver
      nanoparticle-based colorimetric assay.
AB  - The first use of silver nanoparticles (AgNPs) for the rapid, simple, and
      selective determination of homocysteine (Hcy) levels in human plasma was studied.
      Hcy and five other amino acids, including cysteine (Cys), could be distinguished
      by their different aggregation kinetics, which caused a change in the visible
      color and a shift in the UV-vis absorption spectra. The difference in the cross
      linking (aggregation) rate between Hcy and Cys was used as the basis for
      developing a selective probe for Hcy and allowed the detection of Hcy in the
      linear range of 2-12 MUM (R(2)=0.9936). The limits of detection and
      quantification were found to be 0.5 MUM and 1.7 MUM, respectively. To investigate
      its selectivity and potential applicability, this AgNP-based method was
      successfully applied for the determination of Hcy levels in actual biological
      (human plasma) samples, where the determined levels of Hcy were within the error
      range of the measured level using the traditional chemiluminescence microparticle
      immunoassay (CMIA). Thus, the use of AgNPs is a feasible and potentially reliable
      method for the determination of Hcy levels in biological samples.

PMID- 21726713
TI  - Non-target screening of organic contaminants in marine salts by gas
      chromatography coupled to high-resolution time-of-flight mass spectrometry.
AB  - Gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF MS) has
      been applied to characterize the organic pollution pattern of marine salt samples
      collected in saltworks from the Spanish Mediterranean coast. After dissolving the
      samples in water, a solid-phase extraction was applied reaching with a 250
      preconcentration factor. The screening methodology allowed the detection of
      sample components without any kind of pre-selection of target pollutants. The
      identity of components detected was established by accurate mass measurements and
      comparison of experimental full-acquisition spectra with theoretical MS
      libraries. Several organic pollutants were identified in the samples, like
      plasticizers - potentially toxic to humans - and fragrances -included within the
      group of pharmaceuticals and personal care products-, among others. Our results
      indicate that these contaminants can be found in the marine salt after the
      crystallization process. GC-TOF MS is a powerful technique for wide-scope
      screening of (semi)volatile, low-polar organic contaminants, able to investigate
      the presence of a large number of compounds. Searching of contaminants is not
      restricted to a target list of compounds. Therefore, unexpected contaminants can
      be discovered in an efficient way, with better sensitivity and selectivity than
      other conventional analytical techniques, and making use of the powerful
      qualitative information provided by full-spectrum acquisition at accurate mass.

PMID- 21726714
TI  - Development of a novel method combining HPLC fingerprint and multi-ingredients
      quantitative analysis for quality evaluation of traditional Chinese medicine
      preparation.
AB  - A novel method combining high performance liquid chromatography (HPLC)
      fingerprint and simultaneous quantitative analysis of multiple active components
      was developed and validated for quality evaluation of one type of traditional
      Chinese medicine preparations: Shuang-huang-lian (SHL) oral liquid formulation.
      For fingerprint analysis, 45 peaks were selected as the common peaks to evaluate
      the similarities among several different SHL oral liquid preparations collected
      from manufacturers. Additionally, simultaneous quantification of eleven markers,
      including chlorogenic acid, caffeic acid, rutin, forsythiaside, scutellarin,
      baicalin, forsythin, luteoloside, apigenin, baicalein and wogonin, was performed.
      Statistical analysis of the obtained data demonstrated that our method has
      achieved desired linearity, precision and accuracy. Finally, concentrations of
      these eleven markers in SHL oral liquid prepared by different manufacturers in
      China were determined. These results demonstrated that the combination of HPLC
      chromatographic fingerprint and simultaneous quantification of multi-ingredients
      offers an efficient and reliable approach for quality evaluation of SHL oral
      liquid preparations.

PMID- 21726715
TI  - Development of cloud point extraction using pH-sensitive hydrogel for
      preconcentration and determination of malachite green.
AB  - A novel and sensitive cloud point extraction procedure using pH-sensitive
      hydrogel was developed for preconcentration and spectrophotometric determination
      of trace amounts of malachite green (MG). In this extraction method, appropriate
      amounts of poly(styrene-alt-maleic acid), as a pH-sensitive hydrogel, and HCl
      were added respectively into the aqueous sample so a cloudy solution was formed.
      The cloudy phase consists of hydrogel particles distributed entirely into the
      aqueous phase. Organic or inorganic compounds having the potential to interact
      with polymer particles (chemical interaction or physical adsorption) could be
      extracted to cloudy phase. After centrifuging, these particles of hydrogel were
      sedimented in the bottom of sample tube. The sedimented hydrogel-rich phase was
      diluted with acetonitrile and its absorbance was measured at 617 nm (lambda(max)
      of malachite green in hydrogel). Central composite design and response surface
      method were applied to design the experiments and optimize the experimental
      parameters such as, concentration of hydrogel and HCl, extraction time and
      salting out effect. Under the optimum conditions, the linear range was 1 * 10(-8)
      5 * 10(-7)mol L(-1) malachite green with a correlation coefficient of 0.992. The
      limit of detection (S/N=3) was 4.1 * 10(-9) mol L(-1). Relative standard
      deviation (RSD) for 7 replicate determinations of 10(-7) mol L(-1) malachite
      green was 3.03%. In this work, the concentration factor of 20 was reached. Also
      the improvement factor of the proposed method was 23. The advantages of this
      method are simplicity of operation, rapidity and low cost.

PMID- 21726716
TI  - Investigation of plant hormone level changes in shoot tips of longan (Dimocarpus
      longan Lour.) treated with potassium chlorate by liquid chromatography
      electrospray ionization mass spectrometry.
AB  - The endogenous levels of indole-3-acetic acid (IAA), gibberellins (GAs), abscisic
      acid (ABA) and cytokinins (CKs) and their changes were investigated in shoot tips
      of ten longan (Dimocarpus longan Lour.) trees for off-season flowering until 60
      days after potassium chlorate treatment in comparison with those of ten control
      (untreated) longan trees. These analytes were extracted and interfering matrices
      removed with a single mixed-mode solid phase extraction under optimum conditions.
      The recoveries at three levels of concentration were in the range of 72-112%. The
      endogenous plant hormones were separated and quantified by liquid chromatography
      electrospray ionization-mass spectrometry (LC-ESI-MS). Detection limits based on
      the signal-to-noise ratio ranged from 10 ng mL(-1) for gibberellin A4 (GA4) to
      200 ng mL(-1) for IAA. Within the first week after potassium chlorate treatment,
      dry weight (DW) amounts in the treated longan shoot tips of four gibberellins,
      namely: gibberellin A1(GA1), gibberellic acid (GA3), gibberellin A19 (GA19) and
      gibberellin A20 (GA20), were found to increase to approximately 25, 50, 20 and 60
      ng g(-1) respectively, all of which were significantly higher than those of the
      controls. In contrast, gibberellin A8 (GA8) obtained from the treated longan was
      found to decrease to approximately 20 ng g(-1)DW while that of the control
      increased to around 80 ng g(-1)DW. Certain CKs which play a role in leaf bud
      induction, particularly isopentenyl adenine (iP), isopentenyl adenosine (iPR) and
      dihydrozeatin riboside (DHZR), were found to be present in amounts of
      approximately 20, 50 and 60 ng g(-1)DW in the shoot tips of the control longan.
      The analytical results obtained from the two-month off-season longan flowering
      period indicate that high GA1, GA3, GA19 and GA20 levels in the longan shoot tips
      contribute to flower bud induction while high levels of CKs, IAA and ABA in the
      control longan contribute more to the vegetative development.

PMID- 21726717
TI  - High throughput method for the analysis of cetrizine hydrochloride in
      pharmaceutical formulations and in biological fluids using a tris(2,2'
      bipyridyl)ruthenium(II)-peroxydisulphate chemiluminescence system in a two-chip
      device.
AB  - A fast, economic and sensitive chemiluminescence (CL) method has been developed
      for the analysis of cetrizine hydrochloride (CET) in pharmaceutical formulations
      and in biological fluids. The CL method is based on the oxidation of tris(2,2'
      bipyridyl)ruthenium(II) (Ru (bipy)(3)(2+)) by peroxydisulphate in a two-chip
      device. Up to 180 samples can be analysed per hour, consuming only minute
      quantities of reagents. Three instrumental setups were tested to find the most
      economical, sensitive and high throughput setup. In the first setup, a continuous
      flow of sample and CL reagents was used, whereas in the second setup, a fixed
      volume (2 MUL) of (Ru (bipy)(3)(2+)) was introduced into a continuous infusion of
      peroxydisulphate and the sample. In the third design, a fixed volume of sample (2
      MUL) was injected while the CL reagents were continuously infused. Compared to
      the first setup, a 200% signal enhancement was observed in the third setup.
      Various parameters that influence the CL signal intensity, including pH, flow
      rates and reagent concentrations, were optimized. A linear response was observed
      over the range of 50 MUg L(-1) to 6400 MUg L(-1) (R(2)=0.9959) with RSD values of
      1.1% (n=15) for 1000 MUg L(-1). The detection limit was found to be 15 MUg L(-1)
      (S/N=3). The amount of consumed sample was only 2 MUL, from which the detected
      amount of CET was found to be 6.5 * 10(-14)mol. This procedure was successfully
      applied to the analysis of CET in pharmaceutical formulations and biological
      fluids.

PMID- 21726718
TI  - Comparative study of 2-hydroxy propyl beta cyclodextrin and calixarene as
      ionophores in potentiometric ion-selective electrodes for neostigmine bromide.
AB  - Three novel neostigmine bromide (NEO) selective electrodes were investigated with
      2-nitrophenyl octyl ether as a plasticiser in a polymeric matrix of polyvinyl
      chloride (PVC). Sensor 1 was fabricated using tetrakis(4-chlorophenyl)borate
      (TpClPB) as an anionic exchanger without incorporation of an ionophore. Sensor 2
      used 2-hydroxy propyl beta-cyclodextrin as an ionophore while sensor 3 was
      constructed using 4-sulfocalix-8-arene as an ionophore. Linear responses of NEO
      within the concentration ranges of 10(-5) to 10(-2), 10(-6) to 10(-2) and 10(-7)
      to 10(-2) mol L(-1) were obtained using sensors 1, 2 and 3, respectively.
      Nernstian slopes of 51.6 +/- 0.8, 52.9 +/- 0.6 and 58.6 +/- 0.4 mV/decade over
      the pH range of 4-9 were observed. The selectivity coefficients of the developed
      sensors indicated excellent selectivity for NEO. The utility of 2-hydroxy propyl
      beta-cyclodextrin and 4-sulfocalix[8]arene as ionophores had a significant
      influence on increasing the membrane sensitivity and selectivity of sensors 2 and
      3 compared to sensor 1. The proposed sensors displayed useful analytical
      characteristics for the determination of NEO in bulk powder, different
      pharmaceutical formulations, and biological fluids (plasma and cerebrospinal
      fluid (CSF)) and in the presence of its degradation product (3
      hydroxyphenyltrimethyl ammonium bromide) and thus could be used for stability
      indicating methods.

PMID- 21726719
TI  - Determination of polycyclic aromatic hydrocarbons (PAHs) from organic aerosols
      using hollow fiber micro-porous membrane liquid-liquid extraction (HF-MMLLE)
      followed by gas chromatography-mass spectrometry analysis.
AB  - A method for determination of polycyclic aromatic hydrocarbons (PAHs) from
      aerosols was developed. Instead of conventionally used non-polar or slightly
      polar phenylmethylpolysiloxane column a highly polar, highly substituted,
      cyanopropyl column (VF-23 MS) was used for separation of PAHs. Based on hollow
      fiber micro-porous membrane liquid-liquid extraction (HF-MMLLE) a method was
      developed for sample clean up and pretreatment. An enrichment factor of 617-1022
      was obtained with extraction efficiency 10.2-18.9% for different PAHs analyzed in
      this study. The optimized method was successfully applied to aerosol samples and
      limits of detection between 1.2 pg m(-3) and 180 pg m(-3) was obtained. Almost
      all PAHs were found in most of the aerosol samples.

PMID- 21726720
TI  - Electrochemical impedance spectroscopy as a highly sensitive tool for a dynamic
      interaction study between heparin and antithrombin: a novel antithrombin sensor.
AB  - Specific recognition between two biological partners is widely exploited in
      biosensors nowadays. To explore this avenue, a novel biosensor for antithrombin
      (AT) detection was constructed. Heparin was used as the affinity ligand. A well
      known acrylic monomer (butyl methacrylate) was polymerized and grafted onto the
      heparin polysaccharide by the use of ceric ammonium nitrate as a redox initiator
      in aqueous nitric acid medium. Polymers were deposited as a thin layer onto
      surface of stainless steel electrode (SS316L). The obtained polymers were studied
      by Fourier transform infrared spectroscopy (FTIR) and analyzed by differential
      scanning calorimetry (DSC). Moreover, the films were characterized by
      electrochemical impedance spectroscopy (EIS), contact-angle measurements and AFM.
      EIS was used to study the biosensor affinity to AT and the relationship between
      functionalization growth of modified electrode and the response of the sensor.
      The proposed approach appears to be simple, sensitive and correlated with methods
      that analyse the detection of antithrombin.

PMID- 21726721
TI  - Synthesis and cell uptake of a novel dualmodality (188)Re-HGRGD (D) F-CdTe QDs
      probe.
AB  - A novel dualmodality probe was prepared by linking (188)Re-HGRGD (D) F with CdTe
      QDs, which was monitored using radio-thin layer chromatography (TLC) and -high
      performance liquid chromatography (HPLC). The (188)Re-HGRGD (D) F-CdTe QDs probe
      possesses a radiochemistry yield of 92.1% and strong photoluminescence (PL)
      stability. However, the radiochemical purity of (188)Re-HGRGD (D) F-QDs would
      reduce to 74.8%, which should be further improved, after incubation with newborn
      calf serum (NCF) for 24h. Human glioblastoma U87MG cells, known to express a high
      affinity to RGD, were used to assess the in vitro cell binding of probe. The
      results showed that the radio-signal was in accord with the change of PL
      intensity, which meant the successful integration of (188)Re and QDs.

PMID- 21726722
TI  - Low-temperature growth of ZnO nanoparticles: photocatalyst and acetone sensor.
AB  - Well-crystalline ZnO nanoparticles (NPs) were synthesized in large-quantity via
      simple hydrothermal process using the aqueous mixtures of zinc chloride and
      ammonium hydroxide. The detailed structural properties were examined using X-ray
      diffraction pattern (XRD) and field emission scanning electron microscope (FESEM)
      which revealed that the synthesized NPs are well-crystalline and possessing
      wurtzite hexagonal phase. The NPs are almost spherical shape with the average
      diameters of ~ 50 +/- 10 nm. The quality and composition of the synthesized NPs
      were obtained using Fourier transform infrared (FTIR) and electron dispersed
      spectroscopy (EDS) which confirmed that the obtained NPs are pure ZnO and made
      with almost 1:1 stoichiometry of zinc and oxygen, respectively. The optical
      properties of ZnO NPs were investigated by UV-vis absorption spectroscopy.
      Synthesized ZnO NPs were extensively applied as a photocatalyst for the
      degradation of acridine orange (AO) and as a chemi-sensor for the electrochemical
      sensing of acetone in liquid phase. Almost complete degradation of AO has taken
      place after 80 min of irradiation time. The fabricated acetone sensor based on
      ZnO NPs exhibits good sensitivity (~ 0.14065 MUA cm(-2) mM(-1)) with lower
      detection limit (0.068 +/- 0.01 mM) in short response time (10s).

PMID- 21726724
TI  - Potentiometric determination of free acidity in presence of hydrolysable ions and
      a sequential determination of hydrazine.
AB  - A simple potentiometric method for the determination of free acidity in presence
      of hydrolysable ions and sequential determination of hydrazine is developed and
      described. Both free acid and hydrazine are estimated from the same aliquot. In
      this method, free acid is titrated with standard sodium carbonate solution after
      the metal ions in solutions are masked with EDTA. Once the end point for the free
      acid is determined at pH 3.0, an aliquot of formaldehyde is added to liberate the
      acid equivalent to hydrazine which is then titrated with the same standard sodium
      carbonate solution using an automatic titration system. The described method is
      simple, accurate and reproducible. This method is especially applicable to all
      ranges of nitric acid and heavy metal ion concentration relevant to Purex process
      used for nuclear fuel reprocessing. The overall recovery of nitric acid is 98.9%
      with 1.2% relative standard deviation. Hydrazine content has also been determined
      in the same aliquot with a recovery of nitric acid is 99% with 2% relative
      standard deviation. The major advantage of the method is that generation of
      corrosive analytical wastes containing oxalate or sulphate is avoided. Valuable
      metals like uranium and plutonium can easily be recovered from analytical waste
      before final disposal.

PMID- 21726723
TI  - Development of a molecularly imprinted polymer for selective extraction followed
      by liquid chromatographic determination of sitagliptin in rat plasma and urine.
AB  - A novel water-compatible molecularly imprinted solid-phase extraction (MISPE)
      combined with zwitterionic hydrophilic interaction liquid chromatography (ZIC
      HILIC) method for selective extraction and determination of sitagliptin in rat
      serum and urine was developed and validated. The effects of progenic solvents,
      pH, cross linker and amount of monomer were studied to optimize the efficiency
      and selectivity. The adsorption kinetics and isotherms were measured. The
      molecularly imprinted polymer (MIP) showed good specific adsorption capacity with
      an optimum of 180 mg/g at pH 7.5 and selective extraction of sitagliptin from rat
      plasma and urine. The recovery of sitagliptin from rat urine and plasma was >98%.
      The limits of detection (LOD) and quantification (LOQ) were 0.03 and 0.10 MUg/L
      respectively. The proposed method overcomes the matrix effects of phospholipids
      generally encountered while preparation of plasma samples by precipitation of
      proteins.

PMID- 21726725
TI  - Copper nanoparticles entrapped in SWCNT-PPy nanocomposite on Pt electrode as NOx
      electrochemical sensor.
AB  - A highly sensitive NO(x) sensor was designed and developed by electrochemical
      incorporation of copper nanoparticles (CuNP) on single-walled carbon nanotubes
      (SWCNT)-polypyrrole (PPy) nanocomposite modified Pt electrode. The modified
      electrodes were characterized by scanning electron microscopy and energy
      dispersive X-ray analysis. Further, the electrochemical behavior of the CuNP
      SWCNT-PPy-Pt electrode was investigated by cyclic voltammetry. It exhibited the
      characteristic CuNP reversible redox peaks at -0.15 V and -0.3 V vs. Ag/AgCl
      respectively. The electrocatalytic activity of the CuNP-SWCNT-PPy-Pt electrode
      towards NO(x) is four-fold than the CuNP-PPy-Pt electrode. These results clearly
      revealed that the SWCNT-PPy nanocomposite facilitated the electron transfer from
      CuNP to Pt electrode and provided an electrochemical approach for the
      determination of NO(x). A linear dependence (r(2)=0.9946) on the NO(x)
      concentrations ranging from 0.7 to 2000 MUM, with a sensitivity of 0.22 +/- 0.002
      MUA MUM(-1)cm(-2) and detection limit of 0.7 MUM was observed for the CuNP-SWCNT
      PPy-Pt electrode. In addition, the sensor exhibited good reproducibility and
      retained stability over a period of one month.

PMID- 21726726
TI  - Anion recognition through amide-based dendritic molecule: a poly(vinyl chloride)
      based sensor for nitrate ion.
AB  - Poly(vinyl chloride) (PVC)-based membranes of N,N-bis-succinamide-based dendritic
      molecule with tetrabutyl ammonium bromide (TBAB) as a cation inhibitor and
      dibutylphthalate (DBP), dioctylphthalate (DOP), dibutyl (butyl) phosphonate
      (DBBP) and 1-chloronaphthalene (CN) as plasticizing solvent mediators were
      prepared and used as nitrate ion-selective electrodes. Optimum performance was
      observed with the membrane having I-PVC-TBAB-DBP in the ratio 1:33:1:65 (w/w).
      The electrode has a linear response to nitrate with a detection limit of 3.9 *
      10(-5) +/- 0.07 M and Nernstian compliance (57.0 +/- 0.2 mV/decade) between pH
      2.8 and 9.6 with a fast response time of about 20s. The selectivity coefficient
      values of the order of 0.001 for mono-; bi- and trivalent anions; indicate high
      selectivity for nitrate ions over these anions. The preparation procedure of the
      electrode is very easy and inexpensive. The electrodes were used over a period of
      45 days with good reproducibility. The analytical usefulness of the proposed
      electrode has been evaluated by its application in the determination of nitrate
      ions in waste water samples.

PMID- 21726727
TI  - Determination of 48 pesticides and their main metabolites in water samples by
      employing sonication and liquid chromatography-tandem mass spectrometry.
AB  - In this work, a rapid and sensitive analytical multiresidue method has been
      developed for the simultaneous determination of 48 pesticides and 19 metabolites
      in waters (tap, leaching and sewage), using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) with triple quadrupole in selected reaction monitoring
      (SRM) mode. The procedure involves initial single phase extraction of samples
      with acetonitrile by sonication, followed by liquid-liquid partition aided by
      "salting out" process using NaCl. Matrix influence on recoveries was evaluated
      for the three waters. More than 50% of the compound presented very low signal
      suppression. The method presents good linearity over the range assayed 10-500 MUg
      L(-1) and the most frequent detection limits was 0.05 ng mL(-1). The average
      recovery by the LC-MS/MS method obtained for these compounds varied from 74.6 to
      111.2% with a relative standard deviation between 2.5 and 8.9%. The proposed
      method was used to determine pesticides levels in leaching water samples from 5
      lysimeters from an experimental greenhouse located in Murcia.

PMID- 21726728
TI  - A magnesium hydroxide preconcentration/matrix reduction method for the analysis
      of rare earth elements in water samples using laser ablation inductively coupled
      plasma mass spectrometry.
AB  - This paper describes a simple method for simultaneous preconcentration and matrix
      reduction during the analysis of rare earth elements (REEs) in water samples
      through laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).
      From a systematic investigation of the co-precipitation of REEs using magnesium
      hydroxide, we optimized the effects of several parameters - the pH, the amount of
      magnesium, the shaking time, the efficiency of Ba removal, and the sample matrix 
      to ensure quantitative recoveries. We employed repetitive laser ablation to
      remove the dried-droplet samples from the filter medium and introduce them into
      the ICP-MS system for determinations of REEs. The enrichment factors ranged from
      8 to 88. The detection limit, at an enrichment factor of 32, ranged from 0.03 to
      0.20 pg mL(-1). The relative standard deviations for the determination of REEs at
      a concentration of 1 ng mL(-1) when processing 40 mL sample solution were 2.0
      4.8%. We applied this method to the satisfactory determination of REEs in lake
      water and synthetic seawater samples.

PMID- 21726729
TI  - Quantification of anthelmintic drug residues in milk and muscle tissues by liquid
      chromatography coupled to Orbitrap and liquid chromatography coupled to tandem
      mass spectrometry.
AB  - A simple method for the determination of some anthelmintic drugs and
      phenylbutazone residues in milk and muscle was developed. Following a fast and
      easy extraction and evaporation procedure, the extract was injected into an ultra
      performance liquid chromatography system coupled to a single stage Orbitrap
      detector. The high mass resolution of 50,000 full width at half maximum and
      corresponding narrow mass windows permitted a very selective and sensitive
      detection of analytes without requiring fragmentation of the observed [M+H](+) or
      [M+Na](+) ions. This eliminated some difficulties which have plagued the analysis
      of compounds belonging to the group of avermectins. The analytical method was
      validated according to the EU commission decision for Orbitrap based, but also
      for more traditional tandem mass spectrometry based detection and quantification.
      Equal repeatability but significantly higher sensitivity for critical compounds
      (avermectins) was obtained for the Orbitrap based detection. A result of this
      study was the conclusion that analytes with poor fragmentation properties (e.g.
      sodium-cationized molecules) can be more easily quantified by single stage high
      resolution mass spectrometry than by tandem mass spectrometry.

PMID- 21726730
TI  - Hydrazide-functionalized magnetic microspheres for the selective enrichment of
      digested tryptophan-containing peptides in serum.
AB  - The extreme complexity of protein samples is becoming a great challenge for
      proteomic analysis, especially for those having large dynamic range of protein
      abundance. To solve this problem, and to overcome the limitation of the current
      proteomic technologies, a new method using hydrazide-functionalized magnetic
      microspheres was established in this study. With this method, tryptophan (Trp)
      containing peptides can be selectively and sensitively enriched from complex and
      low-volume samples. Furthermore, combined with 1D-LC-MS/MS analysis, the strategy
      was successfully applied to the proteomic study of mouse serum. The proportion of
      Trp-containing peptides was increased from 19.4% to 80.2% through enrichment, and
      the complexity of the sample was reduced more than two times. An additional 113
      Trp-containing peptides and 48 novel proteins were detected compared to the
      conventional method. This enrichment method provides a means for identifying more
      proteins as potential biomarkers in serum and other complex samples.

PMID- 21726731
TI  - Hippocampal metabolomics reveals 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity
      associated with ageing in Sprague-Dawley rats.
AB  - Metabolomics, the exponentially developing technique, could provide a systemic
      mapping in toxicology by directly measuring small molecular metabolites. 2,3,7,8
      Tetrachlorodibenzo-p-dioxin (TCDD) was found to be neurotoxic in mammalian
      animals. In this study, we employed liquid chromatography/quadrupole time-of
      flight mass spectrometry for non-targeted analysis of metabolic profiling in
      hippocampal sample sets of the rats exposed to TCDD. Hippocampal metabolome from
      different ages of the healthy rats (4-week, 12-week and 20-week) was also
      deciphered. The relationship between the two tested cases was unlocked to
      delineate TCDD toxicity associated with ageing. Tandem mass spectrometry
      fragmentation in conjunction with metabolic database searching and compared to
      authentic standards was utilized for metabolite identification. As a consequence,
      the reduced levels of phenylalanine and leucine/isoleucine as well as the up
      regulation of inosine and hypoxanthine were highlighted for understanding of TCDD
      toxicity related to age in rats and the trajectory was depicted by principal
      components analysis.

PMID- 21726732
TI  - Visual detection of melamine in milk samples based on label-free and labeled gold
      nanoparticles.
AB  - Melamine that can cause serious damage to the organs of animal or human beings
      was found to bind to polythymine via hydrogen bonding. With this novel discovery,
      colorimetric detection of melamine based on label-free and labeled gold
      nanoparticles was developed, respectively. Both of the methods revealed good
      selectivity for melamine over other components that may exist in milk and good
      anti-influence ability. The raw milk samples were pretreated according to the
      National standard method combined with a solid phase extraction monolithic
      column. The accurate quantification of melamine as low as 41.7 nM and 46.5 nM was
      obtained, respectively. It also guarantees fast and reliable readout with naked
      eyes, making visual detection possible. Further comparison between label-free and
      labeled based methods was discussed in this paper.

PMID- 21726733
TI  - Square wave voltammetry based on determination of copper (II) ions by
      polyluteolin- and polykaempferol-modified electrodes.
AB  - Applicability of square wave voltammetry for the determination of Cu(II) ions by
      PolyLut/GC and PolyKae/GC electrodes was evaluated in this study. For this
      luteolin and kaempferol were electrochemically polymerized on glassy carbon (GC)
      electrode surface in order to get polyluteolin and polykaempferol-modified glassy
      carbon electrodes (PolyLut/GC and PolyKae/GC, correspondingly). The formation of
      polyphenol layer on the GC electrode surface was evidenced by atomic force
      microscopy. Square wave voltammetry was found to be more sensitive in comparison
      with differential pulse voltammetry. It was determined that PolyLut/GC and
      PolyKae/GC electrodes offered great sensitivity towards Cu(II) ions with very low
      limit of detection, good reproducibility, sufficient stability and excellent
      selectivity of analytical signal.

PMID- 21726734
TI  - Determination of methyltin compounds in urine of occupationally exposed and
      general population by in situ ethylation and headspace SPME coupled with GC-FPD.
AB  - A method for the determination of methyltin compounds in human urine samples was
      developed using headspace solid-phase microextration (HS-SPME) coupled with gas
      chromatographic separation and flame photometric detection. Three methyltin
      compounds, monomethyltin (MMT), dimethyltin (DMT), and trimethyltin (TMT) were in
      situ ethylated by sodium tetraethylborate (NaBEt(4)) for SPME and GC-FPD
      analysis. Under the optimized condition, the detection limits of MMT, DMT, and
      TMT were 8.1, 2.5 and 5.6 ng Sn L(-1), and the relative standard deviations were
      11.0%, 7.3% and 4.0%, respectively. Methyltin compounds in thirteen urine samples
      from occupationally exposed population and two from general population were
      analyzed by the proposed method. The concentrations of total methyltin in the
      tested urine samples of occupationally exposed population ranged from 26.0 to
      7892 ng Sn L(-1), and the average level is higher than those of the two non
      occupationally exposed individuals. The methyltins in urine were adjusted by
      osmolality in order to enhance the comparability of different urine samples and
      the feasibility of this correction method was validated.

PMID- 21726735
TI  - Preparation of an efficient sorbent by washing then pyrolysis of olive wood for
      simultaneous solid phase extraction of chloro-phenols and nitro-phenols from
      water.
AB  - Simultaneous preconcentration of phenol, 2-chlorophenol, 3-chlorophenol, 4
      chlorophenol, 2-nitrophenol, 4-nitrophenol, and 2,4-dinitrophenol was improved by
      using olive wood (OW) washed with ethanol then pyrolyzed at 200 degrees C as
      preconcentrating sorbent. Various OW sorbents were prepared by either washing OW
      (with ethanol, ether, dichloromethane, tetrahydrofuran or n-hexane); or by
      pyrolysis (at 100, 150, 200, 250 or 300 degrees C); or by combined
      pyrolysis/washing. The adsorbents were characterized by elemental analysis, total
      acidity/basicity, methylene blue relative surface area, point of zero charge,
      distribution coefficients of the phenols, and sample loading flow rate. It seems
      that washing and pyrolysis have removed compounds covering the OW pores, which
      improved the OW porosity and exposed more acidic groups on the OW surface. The
      pores and the surface acidic groups seem to play major role in phenols sorption.
      Ethanol-washed OW then pyrolyzed at 200 degrees C gave the best preconcentration
      performance towards phenols (300 mg sorbent, 150 mL of the sample (pH 7), and
      elution with 3 mL of acetonitrile). The method was linear up to 100 MUg L(-1);
      limit of quantification: 0.20-0.48 MUg L(-1). The method could detect phenol and
      2,4-dinitrophenol in industrial wastewater with spiked recovery range from 80.2%
      to 91.4% (+/- 1.1 to 5.5%RSD) for all the phenols.

PMID- 21726736
TI  - Optimization of carrier-mediated three-phase hollow fiber microextraction
      combined with HPLC-UV for determination of propylthiouracil in biological
      samples.
AB  - Carrier-mediated three-phase hollow fiber microextraction combined with high
      performance liquid chromatography-ultra violet detection (HPLC-UV) was applied
      for the extraction and determination of propylthiouracil in biological samples.
      Propylthiouracil (PTU) was extracted from 7.5 mL of the basic solution (the
      source phase) with pH 12 into an organic phase (n-octanol containing 6% (w/v) of
      Aliquat 336 as the carrier) impregnated in the pores of a hollow fiber, and
      finally was back extracted into 24 MUL of the acidic solution located inside the
      lumen of the hollow fiber (the receiving phase). The extraction was performed
      through the gradient of counter ion from the source to the receiving phase. The
      effects of different variables on the extraction efficiency were studied
      simultaneously using an experimental design. A half-fractional factorial design
      was employed for screening to determine the variables significantly affecting the
      extraction efficiency. Then, the factors with significant effect were optimized
      using a central composite design (CCD) and the response surface equations were
      developed. The optimal experimental conditions obtained from this statistical
      evaluation included: source phase, pH 12; temperature, 25 degrees C; extraction
      time, 40 min; counter ion concentration, 2 mol L(-1) of NaClO(4); organic solvent
      6% of Aliquat in octanol and without salt addition in the source phase. Under the
      optimized conditions, the preconcentration factors were between 125 and 198 and
      also the limit of detections (LODs) ranged from 0.1 MUg L(-1) to 0.4 MUg L(-1) in
      different biological samples. The calibration curve was linear (r(2)=0.998) in
      the concentration range of 0.5-1000 MUg L(-1). Finally, the feasibility of the
      proposed method was successfully confirmed by extraction and determination of PTU
      in human plasma and urine as well as the bovine milk and meat samples in
      microgram per liter, and suitable results were obtained (RSDs<6.3%).

PMID- 21726737
TI  - Ferrocene based chemosensor for Cu2+--a dual channel signaling system.
AB  - A new ferrocene based molecule behaves as a dual channel signaling chemosensor
      for Cu(2+) over other metal ions. The perturbations in the absorption pattern and
      electrochemical behavior of the chemosensor are presented. These have been
      proposed to be caused by the interaction of Cu(2+) with the d-electrons and the
      electron rich pi-system of the ferrocenyl derivative. The sensing event is
      manifested by a high energy shift in the ligand centered pi-pi* absorption and
      appearance of a new redox wave at more positive potential, in addition to
      Fe(II)/Fe(III) couple wave (two wave electrochemical behavior).

PMID- 21726738
TI  - In situ copper oxide modified molecularly imprinted polypyrrole film based
      voltammetric sensor for selective recognition of tyrosine.
AB  - Organic-inorganic hybrids are promising functional materials as they combine the
      special characteristics of both organic (polymer) and inorganic phases. Among
      different existing approaches for the preparation of such polymer-inorganic
      hybrid coatings, in situ electrochemical methods are very advantageous because of
      their high sensitivity and simplicity. In the present study, voltammetric sensors
      for tyrosine are designed and developed via various modifications on glassy
      carbon electrode such as polypyrrole coated GCE, molecularly imprinted
      polypyrrole coated GCE (MIPPy) and in situ copper oxide modified MIPPy coated
      GCE. Of these, in situ copper oxide modified MIPPy coated GCE sensor responds to
      tyrosine concentrations in the range 1 * 10(-8) to 1 * 10(-6) and 2 * 10(-6) to 8
      * 10(-6)M with a very low detection limit of 4.0 * 10(-9)M and by far the most
      sensitive one. Detailed linear sweep voltammetric and chronoamperometric
      experiments were undertaken to investigate the electrocatalytic behavior of
      tyrosine. The electron transfer coefficient, diffusion coefficient and charge
      transfer rate constants involved in the sensing process using in situ copper
      oxide modified MIPPy film coated GCE are 0.47, 1.88 * 10(-6)cm(2)s(-1), 4.7 *
      10(6) L mol(-1)s(-1), respectively. Furthermore, the designed sensor is highly
      selective and has been applied successfully for the analysis of synthetic and
      real samples of human urine.

PMID- 21726739
TI  - Determination of arsenic based on quenching of CdS quantum dots fluorescence
      using the gas-diffusion flow injection method.
AB  - A sequential injection analysis system for determination of arsenic based on
      hydride generation and fluorescence quenching of mercaptoacetic acid capped
      cadmium sulfide quantum dots (CdS-MAA QDs) is described. The generated arsine
      diffused across the PTFE membrane in a gas-diffusion unit and subsequently
      interacted with CdS-MAA QDs. The parameters affecting the arsine generation and
      the fluorescence quenching of QDs were studied. Under the optimum conditions, it
      was observed that a increase in the concentration of As(III) corresponded well to
      a decrease in fluorescence intensity according to the Stern-Volmer relationship.
      The extent of quenching was dependent on the concentration of arsenic in the
      range of 0.08-3.20 mmol L(-1), with the detection limit of 0.07 mg L(-1). The
      precision (%RSD) from eight replicates of the determination of As(III) 1.0 mg L(
      1) was found to be 1.4%. The proposed method was applied to the determination of
      arsenic in ground water samples with satisfactory recoveries.

PMID- 21726740
TI  - An ultrasensitive immunosensor array for determination of staphylococcal
      enterotoxin B.
AB  - Staphylococcal enterotoxin B (SEB) is a potent gastrointestinal toxin and is heat
      resistant. SEB is also a potential bioterrorism agent. The ability to measure
      accurately very low amounts of staphylococcal enterotoxin B in food and other
      samples is very important. A highly sensitive and stable sandwich fluorescence
      immunoassay based on a pair of monoclonal antibodies against SEB which were
      produced by us was developed. Classical sandwich immunoassay was adopted and the
      glass slides were used as the base of the immunologic reaction. The
      functionalized fluorescent core-shell silica nanoparticles were used as labels.
      The fluorescence issued from the labels was detected by a laser-induced
      fluorescence millimeter sensor array detection platform. The fluorescence
      intensity has a linear relationship with the amount of SEB in the range of 50
      pg/mL-5 ng/mL, and the detection limit of SEB was 20 pg/mL (the absolute
      detection limit was 0.02 pg). The relative standard deviation (RSD) for 5
      parallel measurements of SEB (1 ng/mL) was 9.2%.

PMID- 21726741
TI  - Fluorometric method for the determination of hydrogen peroxide and glucose with
      Fe3O4 as catalyst.
AB  - In this paper, we utilized the instinct peroxidase-like property of Fe(3)O(4)
      magnetic nanoparticles (MNPs) to establish a new fluorometric method for
      determination of hydrogen peroxide and glucose. In the presence of Fe(3)O(4) MNPs
      as peroxidase mimetic catalyst, H(2)O(2) was decomposed into radical that could
      quench the fluorescence of CdTe QDs more efficiently and rapidly. Then the
      oxidization of glucose by glucose oxidase was coupled with the fluorescence
      quenching of CdTe QDs by H(2)O(2) producer with Fe(3)O(4) MNPs catalyst, which
      can be used to detect glucose. Under the optimal reaction conditions, a linear
      correlation was established between fluorescence intensity ratio I(0)/I and
      concentration of H(2)O(2) from 1.8 * 10(-7) to 9 * 10(-4)mol/L with a detection
      limit of 1.8 * 10(-8)mol/L. And a linear correlation was established between
      fluorescence intensity ratio I(0)/I and concentration of glucose from 1.6 * 10(
      6) to 1.6 * 10(-4)mol/L with a detection limit of 1.0 * 10(-6)mol/L. The proposed
      method was applied to the determination of glucose in human serum samples with
      satisfactory results.

PMID- 21726742
TI  - Ultrasonic nebulization extraction coupled with headspace single-drop
      microextraction of volatile and semivolatile compounds from the seed of Cuminum
      cyminum L.
AB  - Ultrasonic nebulization extraction (UNE) coupled with headspace single-drop
      microextraction (HS-SDME) was developed. In the UNE process, the analytes were
      transferred from the aqueous phase to the gas phase. Then the analytes were
      transferred from the gas phase to the solvent phase by the carrier gas and
      extracted and enriched with suspended microdrop solvent. Finally, the microdrop
      solvent injected into GC-MS system. The parameters affecting extraction
      performance, such as type of suspended solvent, microdrop volume, flow rate of
      carrier gas, temperature of extraction vessel and extraction time were
      investigated and optimized. The proposed method can be applied for the extraction
      and enrichment of the volatile and semivolatile compounds simultaneously. The
      extraction efficiency of the proposed method was compared with that of ultrasonic
      extraction (UE) and UE-HS-SDME. Compared with UE-HS-SDME, the contents of
      constituents in the extract obtained by the proposed method were closer to those
      obtained by hydrodistillation (HD), which is a standard extraction method.

PMID- 21726743
TI  - Identification and determination of carboxylic acids in food samples using 2-(2
      (anthracen-10-yl)-1H-phenanthro[9,10-d]imidazol-1-yl)ethyl 4
      methylbenzenesulfonate (APIETS) as labeling reagent by HPLC with FLD and APCI/MS.
AB  - A new labeling reagent for carboxylic acids, 2-(2-(anthracen-10-yl)-1H
      phenanthro[9,10-d]imidazol-1-yl)ethyl 4-methylbenzenesulfonate (APIETS) has been
      designed and synthesized. It was used to label eight fatty acids (lauric acid,
      myristic acid, palmitic acid, stearic acid, arachidic acid, oleic acid, linoleic
      acid and linolenic acid) and four hydroxy pentacyclic triterpene acids (oleanolic
      acid, ursolic acid, betulinic acid and maslinic acid), successfully. APIETS could
      easily and quickly label carboxylic acids in the presence of K(2)CO(3) catalyst
      at 85 degrees C for 35 min in N,N-dimethylformamide solvent. The carboxylic acids
      derivatives were separated on a C(8) reversed-phase column with gradient elution
      and fluorescence detection at lambda(ex)/lambda(em)=315/435 nm. Identification of
      these derivatives was carried out by online mass spectrometry with atmospheric
      pressure chemical ionization in positive ion mode. The detection limits obtained
      were 13.37-30.26fmol (signal-to-noise ratio of 3). The proposed method has been
      applied to the quantification of carboxylic acids in sultana raisin (Thompson
      seedless), hawthorn flake (Crataegus pinnatifida Bge.), Lycium barbarum seed oil
      and Microula sikkimensis seed oil with recoveries over 95.3%. It has been
      demonstrated that APIETS is a prominent labeling reagent for determining
      carboxylic acids with high performance liquid chromatography.

PMID- 21726744
TI  - Directly suspended droplet microextraction in combination with microvolume UV-vis
      spectrophotometry for determination of phosphate.
AB  - A miniaturized methodology for the determination of phosphate in waters has been
      developed by combining directly suspended droplet microextraction (DSDME) with
      microvolume spectrophotometry. The method is based on the extraction of the ion
      pair formed between 12-molybdophosphate and malachite green onto a microdrop of
      methyl isobutyl ketone and subsequent spectrophotometric determination with no
      dilution. An enrichment factor of 325 was obtained after 7.5 min of
      microextraction. The detection limit was 6.1 nM phosphate and the repeatability,
      expressed as relative standard deviation, was 2.7% (n=6). The method was
      successfully applied to the determination of dissolved reactive phosphorus in
      different freshwater samples.

PMID- 21726745
TI  - Humidity sensing properties of ZnO-based fibers by electrospinning.
AB  - Zinc oxide (ZnO) based fibers with a diameter of 80-100 nm were prepared by
      electrospinning. Polyvinyl alcohol (PVA) and zinc acetate dihydrate were
      dissolved in water and the polymer/salt solution was electrospun at 2.5 kV cm(
      1). The resulting electrospun fibers were subjected to calcination at 500 degrees
      C for 2h to obtain ZnO-based fibers. Humidity sensing properties of the fiber
      mats were investigated by quartz crystal microbalance (QCM) method and electrical
      measurements. The adsorption kinetics under constant relative humidity (RH)
      between 10% and 90% were explained using Langmuir adsorption model. Results of
      the measurements showed that ZnO-based fibers were found to be promising
      candidate for humidity sensing applications at room temperature.

PMID- 21726746
TI  - Ecosystem discrimination and fingerprinting of Romanian propolis by hierarchical
      fuzzy clustering and image analysis of TLC patterns.
AB  - The fingerprinting capacity of thin layer chromatography (TLC) and image analysis
      in the case of propolis samples collected in different area in Romania has been
      investigated. Fuzzy divisive hierarchical clustering approach was used as a
      powerful tool of samples discrimination and fingerprinting according to the
      geographical origin and local flora. The fuzzy partition and patterns obtained by
      membership degrees plot were in a very good agreement with floral origin and
      geographic location of Romanian propolis samples, and clearly illustrate the
      fuzziness concerning their similarities and difference. The results obtained
      strongly support that TLC via image analysis can be successfully employed in the
      fingerprinting methodologies if they are combined with appropriate fuzzy
      clustering method. The method developed in this paper might be also extended in
      the authenticity and origin control of fruits, herbs or derived products.

PMID- 21726747
TI  - Influence of one- and two-dimensional gel electrophoresis procedure on metal
      protein bindings examined by electrospray ionization mass spectrometry,
      inductively coupled plasma mass spectrometry, and ultrafiltration.
AB  - Three independent methods, (i) electrospray ionization mass spectrometry (ESI
      MS), (ii) carrying out the complete protein preparation procedure required for
      protein gel electrophoresis (GE) including extraction, precipitation, washing,
      and desalting with subsequent microwave digestion of the produced protein
      fractions for metal content quantification, and (iii) ultrafiltration for
      separating protein-bound and unbound metal fractions, were employed to elucidate
      the influences of protein sample preparation and GE running conditions on metal
      protein bindings. A treatment of the protein solution with acetone instead of
      trichloroacetic acid or ammonium sulfate for precipitate formation led to a
      strongly enhanced metal binding capacity. The desalting step of the resolubilized
      protein sample caused a metal loss between 10 and 35%. The omission of some
      extraction buffer additives led to a diminished metal binding capacity of protein
      fractions obtained from the sample preparation procedure for GE, whereas a
      tenside addition to the protein solution inhibited metal-protein bindings. The
      binding stoichiometry of Cu and Zn-protein complexes determined by ESI-MS was
      influenced by the type of the metal salt which was applied to the protein
      solution. A higher pH value of the sample solution promoted the metal ion
      complexation by the proteins. Ultrafiltration experiments revealed a higher Cu-
      and Zn-binding capacity of the model protein lysozyme in both resolubilization
      buffers for 1D- and 2D-GE compared to the protein extraction buffer. Strongly
      diminished metal binding capacities of lysozyme were recorded in the running
      buffer of 1D-GE and in the gel staining solutions.

PMID- 21726748
TI  - Enhanced capabilities of separation in Sequential Injection Chromatography--fused
      core particle column and its comparison with narrow-bore monolithic column.
AB  - In the Sequential Injection Chromatography (SIC) only monolithic columns for
      chromatographic separations have been used so far. This article presents the
      first use of fused-core particle packed column in an attempt to extend of the
      chromatographic capabilities of the SIC system. A new fused-core particle column
      (2.7 MUm) Ascentis((r)) Express C18 (SupelcoTM Analytical) 30 mm * 4.6 mm brings
      high separation efficiency within flow rates and pressures comparable to
      monolithic column Chromolith((r)) Performance RP-18e 100-3 (Merck((r))) 100 mm *
      3 mm. Both columns matches the conditions of the commercially produced SIC system
      - SIChromTM (8-port high-pressure selection valve and medium-pressure SapphireTM
      syringe pump with 4 mL reservoir - maximal work pressure 1000 PSI) (FIAlab((r)),
      USA). The system was tested by the separation of four estrogens with similar
      structure and an internal standard - ethylparaben. The mobile phase composed of
      acetonitrile/water (40/60 (v/v)) was pumped isocratic at flow rate 0.48 mL min(
      1). Spectrophotometric detection was performed at wavelength of 225 nm and
      injected volume of sample solutions was 10 MUL. The chromatographic
      characteristics of both columns were compared. Obtained results and conclusions
      have shown that both fused-core particle column and longer narrow shaped
      monolithic column bring benefits into the SIC method.

PMID- 21726749
TI  - Development of a new microextraction method based on a dynamic single drop in a
      narrow-bore tube: application in extraction and preconcentration of some organic
      pollutants in well water and grape juice samples.
AB  - A novel sample preparation technique, the microextraction method based on a
      dynamic single drop in a narrow-bore tube, coupled with gas chromatography-flame
      ionization detection (GC-FID) is presented in this paper. The most important
      features of this method are simplicity and high enrichment factors. In this
      method, a microdrop of an extraction solvent assisted by an air bubble was
      repeatedly passed through a narrow-bore closed end tube containing aqueous
      sample. It has been successfully used for the analysis of some pesticides as
      model analytes in aqueous samples. Parameters affecting the method's performance
      such as selection of extraction solvent type and volume, number of extractions,
      volume of aqueous sample (tube length), and salt effect were studied and
      optimized. Under the optimal conditions, the enrichment factors (EFs) for
      triazole pesticides were in the range of 141-214 and the limits of detection
      (LODs) were between 2 and 112 MUg L(-1). The relative standard deviations (C=1000
      MUg L(-1), n=6) were obtained in the range of 2.9-4.5%. The recoveries obtained
      for the spiked well water and grape juice samples were between 71 and 106%. Low
      cost, relatively short sample preparation time and less solvent consumption are
      other advantages of the proposed method.

PMID- 21726750
TI  - Predicting methylation status of human DNA sequences by pseudo-trinucleotide
      composition.
AB  - DNA methylation plays a key role in the regulation of gene expression. The most
      common type of DNA modification consists of the methylation of cytosine in the
      CpG dinucleotide. The detections of DNA methylation have been determined mostly
      by experimental methods; however, these methods were time-consuming, expensive,
      and difficult to meet the requirements of modern large-scale sequencing
      technology. Accordingly, it is necessary to develop automatic and reliable
      prediction methods for DNA methylation. In this study, the pseudo-trinucleotide
      composition was proposed, and a novel method was developed by support vector
      machine (SVM) with the pseudo-trinucleotide composition as input parameter to
      represent DNA sequence for DNA methylation prediction. The model was evaluated on
      two datasets, including a dataset of Rollins (dataset_1) and a dataset collected
      healthy human records from the MethDB database (dataset_2). For dataset_1, the
      Matthews correlation coefficient (MCC) and accuracy (ACC) by jackknife validation
      were 0.8051 and 0.6098, respectively. For dataset_2, the MCC and ACC were 0.8500
      and 0.7203, respectively. The good prediction results reveal that the pseudo
      trinucleotide composition is an effective representation method for DNA sequence
      and plays a very important role in the prediction of DNA function.

PMID- 21726751
TI  - Electrosorption-enhanced solid-phase microextraction of trace anions using a
      platinum plate coated with single-walled carbon nanotubes.
AB  - A platinum plate coated with single-walled carbon nanotubes (SWCNTs@Pt) was
      prepared by means of electrophoretic deposition. Using the SWCNTs@Pt plate, an
      electrosorption-enhanced solid-phase microextraction (EE-SPME) technique was
      proposed for the extraction of trace anions in water, described as follows: a
      positive potential was applied to the SWCNTs@Pt plate to extract F(-), Cl(-), Br(
      ), NO(3)(-) and SO(4)(2-) from water using electrosorption, and then a negative
      potential was applied to the plate placed in ultra-pure water for the desorption
      of the absorbed anions, and finally the desorbed anions were analyzed using ion
      chromatography (IC). The EE-SPME parameters, including extraction potential and
      time as well as desorption potential and time, were investigated. An analytical
      method based on the above procedures, i.e., EE-SPME-IC, was established and used
      for the analysis of trace anions in water. The results showed that the
      application of potential on the SWCNTs@Pt plate significantly enhanced the ion
      extraction efficiency, and an enrichment factor of 15-38 was achieved. The
      SWCNTs@Pt plate could be used more than 50 times without significant decay. The
      linear range, the limit of detection (S/N=3), the limit of quantification
      (S/N=10) and repeatability (n=7) of our EE-SPME-IC method were 1.0-150.0 MUg/L,
      0.06-0.26 MUg/L, 0.19-0.85 MUg/L and 2.1-8.0%, respectively. The proposed method
      was successfully applied for the analysis of trace anions in deionized water, and
      acceptable recoveries between 65.3 and 121.1% were obtained for the spiked
      deionized water samples.

PMID- 21726752
TI  - Improvements in monitoring the N-terminal valine adduct in human globin after
      exposure to sulfur mustard and synthesis of reference chemicals.
AB  - The N-terminal valine adduct (HETE-Val) in globin is believed to behave as a long
      lived biomarker after exposure to sulfur mustard (HD). Development of a highly
      sensitive method for monitoring HETE-Val, particularly at low HD exposure levels
      or for retrospective detection, would be a significant achievement. In this
      study, by improving the sample preparation method, a sensitive NCI-GC/MS method
      was established for the analysis of HETE-Val in globin after HD exposure. To
      optimize and investigate the sample preparation method, all the relevant HETE-Val
      chemicals were synthesized, purified, and characterized. By carrying out
      optimized solid phase extraction (SPE) cleanup followed by modified Edman
      degradation results in a low detection level and clean baseline. The minimum
      detectable exposure level of human blood (in vitro) to HD is 20 nmol/L (S/N>3).
      The interday and intraday precisions of the proposed method were found to be
      acceptable with less than a 15% relative standard deviation (RSD). A nearly
      linear dose-effect relationship was observed between HETE-Val and a HD exposure
      concentration range of 0.1-120 MUmol/L. The percentage of HD that reacted with N
      terminal valine in globin obtained from human blood (in vitro) was quantified
      using the proposed method.

PMID- 21726753
TI  - Simultaneous detection of five antibiotics in milk by high-throughput suspension
      array technology.
AB  - A new suspension array technology is proposed for the simultaneous quantitative
      determination of five antibiotics-tylosin, tetracycline, gentamicin,
      streptomycin, and chloramphenicol in milk. A novel treatment of milk samples for
      suspension array with diethyl ether was performed which greatly reduced the
      interference of the disturbing components in milk on the reaction results with no
      significant effect on detection sensitivity. Compared with using biotin labeled
      monoclonal antibody, using of secondary antibody-biotin make the detection
      sensitivity further improved. The minimum detectable concentration in samples of
      tylosin, tetracycline, gentamicin, streptomycin, and chloramphenicol were 0.3,
      1.5, 4, 20, and 25 ng/ml, respectively, and the working ranges of samples were 6
      400, 7-300, 8-200, 90-3000 and 70-8000 ng/ml, respectively. The mean recovery was
      89.38-113.73% with a standard deviation within 16.62%. The suspension assay
      technology is powerful for the fast quantitative analysis of multi-antibiotics
      residue in milk.

PMID- 21726754
TI  - Thermo-responsive polymer coated fiber-in-tube capillary microextraction and its
      application to on-line determination of Co, Ni and Cd by inductively coupled
      plasma mass spectrometry (ICP-MS).
AB  - The poly(N-isopropylacrylamide) (PNIPA) gel is a widely studied thermo-responsive
      material that exhibits discontinuous change in volume when the external
      temperature is increased. In this paper, PNIPA gel was prepared and applied as a
      novel polymer coating for fiber-in-tube capillary microextraction of trace Co, Ni
      and Cd followed by on-line ICP-MS detection. The PNIPA coating was synthesized by
      using ethylene triethoxysilane (ETEOS) as the cross-linking agent under acidic
      conditions. This siloxane incorporated PNIPA gel achieves a dramatically rapid
      response rate when the external temperature is changed. The micro-structure of
      PNIPA coating was examined by scanning electron micrograph (SEM). Various
      experimental parameters including pH, temperature, sample flow rate and volume,
      elution solution and interfering ions affecting the extraction of the target
      analytes have been carefully investigated and optimized. Under the optimized
      conditions, the limits of detection were 0.45, 4.6 and 6.9 ng L(-1) for Co, Ni
      and Cd, respectively. With a sampling frequency of 13 h(-1), the relative
      standard deviations (RSDs) for Co, Ni and Cd were 4.8, 5.1 and 6.4% (C=1 MUg L(
      1), n=7), respectively. The proposed method had been successfully applied to the
      determination of Co, Ni and Cd in human urine. To validate the proposed method,
      certified reference materials of NIES No. 10-b rice flour and GBW07601 (GSH-1)
      human hair were analyzed and the determined values were in a good agreement with
      the certified values. The PNIPA coated fiber-in-tube capillary can be reused for
      more than 150 times without decreasing the extraction efficiency.

PMID- 21726755
TI  - Bio-electrocatalysis of NADH and ethanol based on graphene sheets modified
      electrodes.
AB  - Characterization and application of graphene sheets modified glassy carbon
      electrodes (graphene/GC) have been presented for the electrochemical bio-sensing.
      A probe molecule, potassium ferricyanide is employed to study the electrochemical
      response at the graphene/GC electrode, which shows better electron transfer than
      graphite modified (graphite/GC) and bare glassy carbon (GC) electrodes. Based on
      the highly enhanced electrochemical activity of NADH, alcohol dehydrogenase (ADH)
      is immobilized on the graphene modified electrode and displays a more desirable
      analytical performance in the detection of ethanol, compared with graphite/GC or
      GC based bio-electrodes. It also exhibits good performance of ethanol detection
      in the real samples. From the results of electrochemical investigation, graphene
      sheets with a favorable electrochemical activity could be an advanced carbon
      electrode materials for the design of electrochemical sensors and biosensors.

PMID- 21726756
TI  - Preparation of poly(N-isopropylacrylamide)-grafted well-controlled 3D skeletal
      monolith based on E-51 epoxy resin for protein separation.
AB  - A novel type of poly(N-isopropylacrylamide) grafted E-51 epoxy-based monoliths in
      a 100 mm * 4.6mm I.D. stainless steel column with well-controlled three
      dimensional skeletal structures has been prepared and proposed for the separation
      of proteins. The grafted PNIPAAm chain via surface-initiated atom transfer
      radical polymerization was successfully performed. The proposed method provided a
      new route to modify the E-51 epoxy-based monoliths for widening their
      applications. Meanwhile, the temperature and the salt concentration responses of
      the grafted monolithic columns were investigated. Under the salt gradient, six
      proteins were well separated in hydrophobic interaction mode. Moreover, for
      further confirming the application of the prepared monolith was meaningful for
      proteome analysis in actual system, the separation of human serum sample was
      performed.

PMID- 21726757
TI  - Rhodamine B aggregation in self-assembled multilayers induced by polyelectrolyte
      and interfacial fluorescence recognition for DNA.
AB  - Photophysical properties of Rhodamine B bound to water-soluble polyanion sodium
      poly(4-styrenesulfonate) (PSS) in solution and Quartz/APES/PSS/RB SAMs were
      investigated. Experiments showed that Rhodamine B aggregated in
      Quartz/APES/PSS/RB SAMs and its fluorescence behavior was different from that in
      Quartz/APES/RB SAMs without PSS. The constructed Quartz/APES/PSS/RB SAMs were
      applied for label-free interfacial fluorescence sensing of DNA with extremely
      high sensitivity.

PMID- 21726758
TI  - Investigation of temperature-responsivity and aqueous chromatographic
      characteristics of a thermo-responsive monolithic column.
AB  - A thermo-responsive and macroporous monolithic cryogel was directly prepared by
      in situ free-radical redox cryo-polymerization in a stainless steel
      chromatographic column (100 mm * 4.6mm i.d.) using N-isopropylacrylamide (NIPAAm)
      as functional monomer and PEG-20,000 as porogen at -12 degrees C. The internal
      morphology of resulting monolithic cryogel was estimated by scanning electron
      microscopy (SEM). Based on that, a submicron skeleton structure was observed.
      Besides, the gravimetrically determined rates of swelling/deswelling for thermo
      responsive monolithic cryogel were much higher than that of hydrogel adopting the
      same component proportion via conventional method (25 degrees C for 24h).
      Simultaneously, a temperature-dependent resolution of steroids was also achieved
      using only water as a mobile phase. The theoretical plate number of every analyte
      was more than 2000.

PMID- 21726759
TI  - Use of ionic liquid aggregates of 1-hexadecyl-3-butyl imidazolium bromide in a
      focused-microwave assisted extraction method followed by high-performance liquid
      chromatography with ultraviolet and fluorescence detection to determine the 15+1
      EU priority PAHs in toasted cereals ("gofios").
AB  - A focused-microwave assisted extraction method using aggregates of the ionic
      liquid (IL) 1-hexadecyl-3-butylimidazolium bromide (HDBIm-Br) followed by high
      performance liquid chromatography (HPLC) with ultraviolet (UV) detection and
      single-channel fluorescence detection (FLD) has been developed for the
      determination of polycyclic aromatic hydrocarbons (PAHs) in toasted cereals
      ("gofios") of different nature (wheat, barley, rye, and maize corn) from the
      Canary Islands, Spain. The optimized HPLC-UV-vis/single-channel FLD method takes
      40 min for the chromatographic run with limits of detection varying between 0.02
      and 4.01 ng mL(-1) for the fluorescent PAHs from the European Union (EU) priority
      list in foods, and 20.5 ng mL(-1) for the non-fluorescent PAH
      cyclopenta[c,d]pyrene (CPP). The optimized microwave step presented extractions
      recoveries ranging from 70.1 to 109% and precision values lower than 12.6% (as
      relative standard deviation), using an extraction time of 14 min. The extraction
      method also utilizes low amounts of sample (0.1g), and low amounts of IL (77 mg),
      avoiding completely the use of organic solvents.

PMID- 21726760
TI  - A new amperometric bienzymatic biosensor based on biocomposites for the
      determination of gluconic acid in wines.
AB  - A new amperometric bienzymatic biosensor for gluconic acid based on the
      coimmobilization of gluconokinase (EC 2.7.1.12) and phosphogluconate
      dehydrogenase (EC 1.1.1.44) by polysulfone membrane entrapment onto the surface
      of a graphite-epoxy composite is reported. This biosensor represents an
      alternative to gluconate dehydrogenase (EC 1.1.99.3) based methods, which is no
      longer commercially available. Measurements were done at an applied potential of
      +0.800 V, room temperature and phosphate buffer pH 7.50; obtaining a linear
      response range for gluconic acid extended from 7.0 * 10(-6) to 2.5 * 10(-4)M.
      Constructed biosensors showed good reproducibility for calibrations using
      different electrodes (RSD of 1.74%). Finally, biosensor was applied to real wine
      samples, and the results obtained were validated by comparison with those
      provided by a reference laboratory. Good correlation was found when the biosensor
      results were plotted vs. the reference values (slope=1.03 +/- 0.04,
      intercept=0.01 +/- 0.02, r(2)=0.995).

PMID- 21726761
TI  - Application of manganese (II) phthalocyanine synthesized in situ in the SiO2/SnO2
      mixed oxide matrix for determination of dissolved oxygen by electrochemical
      techniques.
AB  - This work describes the in situ immobilization of Mn(II) phthalocyanine (MnPc) in
      a porous SiO(2)/SnO(2) mixed oxide matrix obtained by the sol gel processing
      method. The chemically modified matrix SiO(2)/SnO(2)/MnPc, possessing an
      estimated amount of 8 * 10(-10) mol cm(-2) of MnPc on the surface, was used to
      prepare an electrode to analyze dissolved oxygen in water by an electrochemical
      technique. The electrode was prepared by mixing the material with ultrapure
      graphite and evaluated using differential pulse voltammetry. Dissolved O(2) was
      reduced at -0.31 V with a limit of detection (LOD) equal to 7.0 * 10(-4) mmol L(
      1). A mechanism involving four electrons in O(2) reduction was determined by the
      rotating disk electrode technique.

PMID- 21726762
TI  - Extractive spectrophotometric determination of palladium with N,N,N',N'-tetra(2
      ethylhexyl)-thiodiglycolamide T(2EH)TDGA.
AB  - A precise, sensitive and selective method for the spectrophotometric
      determination of palladium (II) using N,N,N',N'-tetra(2-ethylhexyl)
      thiodiglycolamide T(2EH)TDGA as an extractant is described. Palladium (II) forms
      yellow colored complex with T(2EH)TDGA which exhibits an absorption maximum at ~
      300 nm. The colored complex obeys Beer's law in the concentration range 1.0-15.0
      MUg ml(-1) of palladium with a molar absorptivity of 1.29 * 10(5)M(-1)cm(-1). The
      effects of various experimental parameters have been studied to establish the
      optimum conditions for the extraction and determination of palladium. The
      precision of the method has been evaluated and the relative standard deviation
      has been found to be less than 0.5%. The method has been successfully applied to
      the determination of palladium in simulated high level liquid waste (SHLW)
      solution.

PMID- 21726763
TI  - Development and validation of an HPLC-PDA method for the determination of
      myrsinoic acid B in the extracts of Rapanea ferruginea Mez.
AB  - New, simple, rapid and precise HPLC-PDA method has been developed and validated
      for quantification of biomarker myrsinoic acid B in stem bark extracts of Rapanea
      ferruginea Mez. The method employs a Phenomenex C18 column (250 mm * 4.6mm I.D.,
      5 MUm) with acetonitrile:methanol:water (pH 2.6 with phosphoric acid) at 48:30:22
      as mobile phase, at a flow rate of 0.7 mL min(-1) and photo diode array (PDA)
      detection at 270 nm. The validation data show that the method is specific,
      accurate, precise and robust. The method was linear, over a range of 5-100.0 MUg
      mL(-1), with a limit of detection of 0.369 MUg mL(-1) and limit of quantification
      of 1.233 MUg mL(-1). The method has also shown consistent recoveries (average of
      101.3% and 0.12% RSD) of the biomarker, with low intra and inter-day relative
      standard deviation (1.26% and 1.62%, respectively). The evaluated hydroethanolic
      extract and dry extract presented MAB values of 63.53 and 36.07 mg g(-1),
      respectively.

PMID- 21726764
TI  - Use of 3-D plots to avoid mutual interference in bianalyte ASV determinations:
      application to cadmium and lead detection.
AB  - We have examined the anodic stripping voltammetry (ASV) of Cd and Pb at carbon
      screen printed electrodes modified by an in situ deposited Bi film, and have
      demonstrated significant cross talk between the stripping peaks of the two
      metals. A simple and generally applicable method for dealing with this problem is
      described, based on curve-fitting three-dimensional calibration plots using
      MATLAB. Non-linear fitting to the calibrations produced coefficients of
      determination R(2)>0.99 for both metals. We have illustrated use of the plots in
      conjunction with Bi-plated electrodes by measuring 15 randomly selected mixtures
      of Cd and Pb of known concentration.

PMID- 21726765
TI  - Photocytotoxic activity of a nitrosyl phthalocyanine ruthenium complex--a system
      capable of producing nitric oxide and singlet oxygen.
AB  - The synthesis, structural aspects, pharmacological assays, and in vitro
      photoinduced cytotoxic properties of [Ru(NO)(ONO)(pc)] (pc=phthalocyanine) are
      described. Its biological effect on the B16F10 cell line was studied in the
      presence and absence of visible light irradiation. At comparable irradiation
      levels, [Ru(NO)(ONO)(pc)] was more effective than [Ru(pc)] at inhibiting cell
      growth, suggesting that occurrence of nitric oxide release following singlet
      oxygen production upon light irradiation may be an important mechanism by which
      the nitrosyl ruthenium complex exhibits enhanced biological activity in cells.
      Following visible light activation, the [Ru(NO)(ONO)(pc)] complex displayed
      increased potency in B16F10 cells upon modifications to the photoinduced dose;
      indeed, enhanced potency was detected when the nitrosyl ruthenium complex was
      encapsulated in a drug delivery system. The liposome containing the
      [Ru(NO)(ONO)(pc)] complex was over 25% more active than the corresponding
      ruthenium complex in phosphate buffer solution. The activity of the complex was
      directly proportional to the ruthenium amount present inside the cell, as
      determined by inductively coupled plasma mass spectroscopy. Flow cytometry
      analysis revealed that the photocytotoxic activity was mainly due to apoptosis.
      Furthermore, the vasorelaxation induced by [Ru(NO)(ONO)(pc)], proposed as NO
      carrier, was studied in rat isolated aorta. The observed vasodilation was
      concentration-dependent. Taken together, the present findings demonstrate that
      the [Ru(NO)(ONO)(pc)] complex induces vascular relaxation and could be a potent
      anti-tumor agent. Nitric oxide release following singlet oxygen production upon
      visible light irradiation on a nitrosyl ruthenium complex produces two radicals
      and may elicit phototoxic responses that may find useful applications in
      photodynamic therapy.

PMID- 21726766
TI  - A protective protein matrix improves the discrimination of nitroxyl from nitric
      oxide by MnIII protoporphyrinate IX in aerobic media.
AB  - The selectivity of MnIII/II porphyrinates toward nitroxyl or nitric oxide donors
      provides a convenient starting point for the development of new materials for the
      speciation of these nitrogen-containing redox relatives. In the present report,
      we describe the insertion of MnIII protoporphyrinate IX in apomyoglobin and its
      chemical behavior toward HNO or NO donors, either under anaerobic or aerobic
      conditions. For comparison and discussion, the MnIII porphyrinate, devoid of the
      protein matrix, was studied in parallel. The MnIII reconstituted globin
      successfully reacted with the nitroxyl donor trioxodinitrate, while it was
      unreactive toward NO or NO donors, in good agreement with previously reported
      data on water soluble MnIII porphyrinates. The estimated association rate
      constant for the reaction with the nitroxyl donor was of the same order of
      magnitude for the reconstituted globin and the free porphyrinate, suggesting that
      the protein environment is not involved in the reaction mechanism. In contrast,
      the reaction product exhibited enhanced stability in the presence of dioxygen
      only when the porphyrinate was included in the protein matrix; this feature is
      ascribed to the role of the distal residues on the metal centered reactivity.
      This behavior is required for spectroscopic detection under biologically relevant
      conditions.

PMID- 21726767
TI  - Comparative genomics analysis of metallothioneins in twelve Drosophila species.
AB  - Metallothioneins (MTs) are a superfamily of Cys-rich polypeptides that bind heavy
      metal ions, both for physiological and detoxification purposes. They are present
      in all organisms, but their origin is probably polyphyletic, so that MT
      evolutionary studies are rather scarce. We present a thorough search and analysis
      of the MT coding sequences in the 12 Drosophila genomes completely sequenced,
      taking as reference the features reported for D. melanogaster, where four
      isogenes (MtnA to MtnD) are known and deeply characterized. We include a fifth
      isoform in this study, named MtnE, and recently annotated. The MTs polymorphism
      pattern is essentially the same for the 12 Drosophila species. Invariably, a MtnA
      form and an MtnB-cluster, comprising the MtnB-to-MtnE forms in tandem array, are
      observed. The whole set of genes are kept in the same synteny element (Muller E),
      but implicated in rearrangement events (mainly inversions), encompassing all or
      some of the isogenes. Gene exon/intron architecture, and cDNA and protein
      sequences appear highly conserved through Drosophila speciation, concordantly
      with an essential function for MT isoforms in flies, even for those previously
      considered as minor products. Data presented here will be comprehensively
      analyzed to provide a valuable guide for future MT evolutionary, structure and
      function studies.

PMID- 21726768
TI  - Optimization of a biomimetic bone cement: role of DCPD.
AB  - We previously proposed a biomimetic alpha-tricalcium phosphate (alpha-TCP) bone
      cement where gelatin controls the transformation of alpha-TCP into calcium
      deficient hydroxyapatite (CDHA), leading to improved mechanical properties. In
      this study we investigated the setting and hardening processes of biomimetic
      cements containing increasing amounts of CaHPO(4).2H2O (DCPD) (0, 2.5, 5, 10, 15
      wt.%), with the aim to optimize composition. Both initial and final setting times
      increased significantly when DCPD content accounts for 10 wt.%, whereas cements
      containing 15 wt.% DCPD did not set at all. Differential scanning calorimetry
      (DSC), X-ray diffraction (XRD), thermogravimetry (TG) and scanning electron
      microscopy (SEM) investigations were performed on samples maintained in
      physiological solution for different times. DCPD dissolution starts soon after
      cement preparation, but the rate of transformation decreases on increasing DCPD
      initial content in the samples. The rate of alpha-TCP to CDHA conversion during
      hardening decreases on increasing DCPD initial content. Moreover, the presence of
      DCPD prevents gelatin release during hardening. The combined effects of gelatin
      and DCPD on the rate of CDHA formation and porosity lead to significantly
      improved mechanical properties, with the best composition displaying a
      compressive strength of 35 MPa and a Young modulus of 1600 MPa.

PMID- 21726769
TI  - Physiological cholesterol concentration is a neuroprotective factor against beta
      amyloid and beta-amyloid-metal complexes toxicity.
AB  - Alzheimer's disease is one of the most common forms of dementia in the elderly.
      One of its hallmarks is the abnormal aggregation and deposition of beta-amyloid
      (Abeta). Endogenous and exogenous metal ions seem to influence beta-amyloid
      folding process, aggregation and deposition. Besides these variables other
      elements appear to affect beta-amyloid behavior, such as cholesterol. The
      physiological concentration of cholesterol in the cerebrospinal fluid (CSF) was
      used in order to determine the extent in which Abeta and Abeta-metal complexes in
      vitro aggregation and their toxicity on human neuroblastoma cell cultures is
      affected. Cholesterol did not appear to influence Abeta and Abeta-metal complexes
      aggregation, but it was effective in protecting neuroblastoma cells against Abeta
      complexes' toxicity. The Abeta-Al complex seemed to be the most effective in
      disrupting and damaging membrane external layer, and simultaneously it appears to
      increase its toxicity on cell cultures; both of these effects are preventable by
      cholesterol. The presence in physiological concentrations of cholesterol seemed
      to compensate membrane damage that occurred to neuroblastoma cells. These
      findings appear to contradict some data reported in literature. We believe that
      our results might shed some light on the role played by cholesterol at
      physiological concentrations in both cellular balance and membrane protection.

PMID- 21726770
TI  - Molecular recognition patterns of 2-aminopurine versus adenine: a view through
      ternary copper(II) complexes.
AB  - In contrast to the comprehensive structural information about metal complexes
      with adenine, the corresponding to its isomer 2-aminopurine (H2AP) is extremely
      poor. With the aim to rationalize the metal binding pattern of H2AP, we report
      the molecular and/or crystal structure of four novel compounds with various
      iminodiacetate-like (IDA-like) copper(II) chelates: [Cu(IDA)(H2AP)(H2O)].H2O (1),
      [Cu(MIDA)(H2AP)(H2O)].3H2O (2), {[Cu(NBzIDA)(H2AP)].1.5H2O}n (3) and
      [Cu(MEBIDA)(H2AP)(H2O)].3.5 H2O (4), where IDA, MIDA, NBzIDA and MEBIDA are R=H,
      CH3, benzyl- and p-tolyl- in R-N-(CH2-COO-)2 ligands, respectively. Synthesis
      strategies include direct reactions of copper(II) chelates with H2AP (alone, for
      1 and 3) and/or with the base pairs H2AP:thymine (1-4) or H2AP:cytosine (3).
      Moreover, these compounds have been also investigated by spectral and thermal
      methods. Regardless of the N-derivative of the IDA chelator, molecular
      recognition between H2AP and the referred Cu(II)-chelates only displays the
      formation of the Cu-N7(purine-like) bond what is clearly in contrast to what was
      previously reported for adenine. The metal binding pattern of 2-aminopurine is
      discussed on the basis of the electronic effects and steric hindrance of the 2
      amino exocyclic group.

PMID- 21726771
TI  - A new salicylic acid-derivatized kojic acid vanadyl complex: synthesis,
      characterization and anti-diabetic therapeutic potential.
AB  - The molecular mechanisms of vanadium toxicity suggest that incorporation of
      antioxidant groups in the structure of vanadium complexes could be a preferable
      strategy in designing novel hypoglycemic vanadium complexes with proper efficacy
      and safety. By conjugating a pyrone skeleton to provide a coordination group and
      antioxidative motifs, we synthesized a novel complex of bis ((5-hydroxy-4-oxo-4H
      pyran-2-yl) methyl 2-hydroxy- benzoatato) oxovanadium (IV) (BSOV). Evaluation of
      the anti-diabetic effects of BSOV using streptozotocin (STZ)-induced diabetic
      rats with bis (maltolato) oxovanadium (BMOV) as a positive control showed that
      BSOV effectively lowered blood glucose level, ameliorated damages of hepatic and
      renal function in diabetic rats and improved lipid metabolism. The signs of
      potential alteration of renal function caused by BSOV and BMOV were observed and
      are discussed. Overall, the experimental results suggest BSOV as a potent
      hypoglycemic agent and further studies using this strategy for anti-diabetic
      agents.

PMID- 21726772
TI  - Remarkable photocytotoxicity in hypoxic HeLa cells by a dipyridophenazine
      copper(II) Schiff base thiolate.
AB  - Copper(II) complexes [Cu(satp)(L)] (1-3) of a Schiff base thiolate (salicylidene
      2-aminothiophenol, H2satp) and phenanthroline bases (L), viz. 1,10-phenanthroline
      (phen in 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2) and dipyrido[3,2
      a:2',3'-c]phenazine (dppz in 3), were prepared, characterized and their anaerobic
      DNA photocleavage activity and hypoxic photocytotoxicity studied. The redox
      active complexes show the Cu(II)-Cu(I) couple near -0.5 V for 1 and near 0.0 V
      vs. SCE (saturated calomel electrode) for 2 and 3. The one-electron paramagnetic
      complexes (~1.85 MUB) are avid DNA binders giving Kb values within 1.0*10(5)
      8.0*10(5) M(-1). Thermal melting and viscosity data along with molecular docking
      calculations suggest DNA groove and/or partial intercalative binding of the
      complexes. The complexes show anaerobic DNA cleavage activity in red light under
      argon via type-I pathway, while DNA photocleavage in air proceeds via hydroxyl
      radical pathway. The DFT (density functional theory) calculations reveal a thyil
      radical pathway for the anaerobic DNA photocleavage activity and suggest the
      possibility of generation of a transient copper(I) species due to bond breakage
      between the copper and sulfur to generate the thyil radical. An oxidation of the
      copper(I) species is likely by oxygen in an aerobic medium or by the buffer
      medium in an anaerobic condition. Complex 3 exhibits significant
      photocytotoxicity in HeLa cells (IC50=8.3(+/-1.0) MUM) in visible light, while
      showing lower dark toxicity (IC50=17.2(+/-1.0) MUM). A significant reduction in
      the dark toxicity is observed under hypoxic cellular conditions (IC50=30.0(+/
      1.0) MUM in dark), while retaining its photocytotoxicity (IC50=8.0(+/-1.0) MUM).

PMID- 21726773
TI  - Antitumor activities and interaction with DNA of oxaliplatin-type platinum
      complexes with linear or branched alkoxyacetates as leaving groups.
AB  - Five oxaliplatin-typed platinum complexes containing trans-1R, 2R
      diaminocyclohexane chelating platinum cores, characteristic of linear or branched
      alkoxycarboxylates as leaving groups, were biologically evaluated. These
      compounds showed higher antitumor activity, lower toxicity in vivo than cisplatin
      or oxaliplatin. And the results revealed that the antitumor activity and
      interaction with DNA of these compounds were highly related to the nature of
      leaving groups. Among these complexes, 5a, cis-(trans-1R, 2R-diaminocyclohexane)
      bis (2-tert-butoxyacetate) platinum(II), showed the highest antitumor activity
      and the lowest toxicity.

PMID- 21726774
TI  - Biological activity and structure dependent properties of cuprous iodide
      complexes with phenanthrolines and water soluble tris (aminomethyl) phosphanes.
AB  - This paper presents the biological activity of copper(I) iodide complexes with
      1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (dmp) and three
      tris (aminomethyl) phosphanes: P(CH2N(CH2CH2)2NCH3)3 (1), P(CH2N(CH2CH2)2O)3 (2)
      and P (CH2N(CH3)CH2CH2OH)3 (3). Crystallographic and DFT data indicate a
      significantly stronger binding ability of 3 in the complexes [CuI (phen) P (CH2N
      (CH3)CH2CH2OH)3] (3P) and [CuI(dmp)P(CH2N(CH3)CH2CH2OH)3] (3N) in comparison to
      the 1 or 2 ligands. Most probably, this is caused by the relatively small steric
      requirements of 3. The complexes with dmp exhibit a very high in vitro activity
      against the Staphylococcus aureus strain (MIC - minimal inhibitory concentration:
      2.5-5 MUg/mL) and Candida albicans diploid fungus (MIC: 1.25-2.5 MUg/mL). All the
      tested complexes also show a strong in vitro antitumor activity against human
      ovarian carcinoma cell lines: MDAH 2774 (IC50: 7-2 MUM) and cisplatin-resistant
      SCOV3 (IC50: 3-2 MUM). Interestingly, the complexes with dmp of higher biological
      activity more weakly interact with bovine serum albumin (BSA) and less
      efficiently cleave the pBluescriptSK+ plasmid.

PMID- 21726775
TI  - Systematic coordination chemistry and cytotoxicity of copper(II) complexes with
      methyl substituted 4-nitropyridine N-oxides.
AB  - Three new nitrato copper(II) complexes of dimethyl substituted 4-nitropyridine N
      oxide were synthesized and characterized by elemental analysis, magnetic,
      spectroscopic, thermal and X-ray methods, respectively. They were isolated as
      trans isomers, mononuclear (MU=1.70-1.88 BM), five (1-2) and four (3) coordinate
      species of general formula [Cu(NO3)2(H2O)L2] where L=2,3-dimethyl-, 2,5-dimethyl
      4-nitropyridine N-oxide and [Cu (NO3)2L2], L=3,5-dimethyl-4-nitropyridine N
      oxide, respectively. The X-ray crystal structure of (1) (L=2,3-dimethyl-4
      nitropyridine N-oxide) was determined. The organic ligands, the complexes and
      copper hexaqua ion as a reference were tested in vitro on the cytotoxic activity
      against human cancer cell lines: MCF-7 (breast), SW-707 (colon) and P-388 (murine
      leukemia). The complexes are relatively strong cytotoxic agents towards P-388
      cell line. Comparative analysis was performed for all known copper(II) complexes
      containing methyl derivatives of the 4-nitropyridine N-oxide on the basis of
      their composition, structure and cytotoxic activities. To obtain the typical
      structure for these species (i.e., 4-coordinate mononuclear of the type trans
      [Cu(inorganic anion)2L2]), two methyl groups must be situated on both sides of
      nitrogen atom(s) (i.e., NO and NO2) in the ligand. The biological activity was
      found to be strongly dependent upon the number of the methyl groups and the type
      of cell line. The best cytotoxic results were found for the complexes without
      substituents or with one methyl group. Generally, for all cell lines, the
      complexation increased cytotoxicity when compared with the free ligands.

PMID- 21726776
TI  - Cyberbullying: the virtual threat.

PMID- 21726777
TI  - Faculty leadership development: concept or reality?

PMID- 21726778
TI  - Effectiveness of a simulation-based educational program in a pediatric cardiac
      intensive care unit.
AB  - Optimal staff performance of resuscitation skills is best achieved through
      regular effective training. However, providing this teaching in a busy high
      acuity pediatric cardiac intensive care unit (ICU) had become a challenge due to
      time and logistical constraints. A program to effectively and efficiently teach
      ICU nurses the skills necessary in patient resuscitation was developed using
      simulation training to better meet staff learning needs. Training via simulation
      provides an ideal learning environment with hands-on experience with the roles
      required in patient resuscitation. A simulation training program incorporating
      simulation training was developed for ICU nursing staff. All staff nurses in the
      ICU were required to attend over a year's time. The program involved mock
      resuscitation scenarios in which participants performed various resuscitation
      roles, followed by video review and group debriefing. All participants completed
      a survey prior to and immediately following participation in the training and
      again at 1 year. Data collected included self-report of knowledge, skill, and
      comfort related to patient resuscitation. Data revealed statistically significant
      improvement in scores pre and post training and at 1 year for self-reported
      knowledge, skills, and comfort related to resuscitation. Nursing staff reported
      that simulation training in resuscitation skills was helpful and positively
      impacted their knowledge, comfort, and skills. Feedback from nursing staff
      continues to be very positive, and performance of actual resuscitations on the
      unit has improved anecdotally.

PMID- 21726779
TI  - Children's experiences of living with asthma: fear of exacerbations and being
      ostracized.
AB  - The aim of the study was to explore children's experiences of asthma to tailor a
      learning program based on their perspectives. Fifteen children (7-10 years) were
      interviewed, and they narrated the meaning behind their drawings; a
      phenomenological hermeneutical approach was used in the analysis. The findings
      are described in two themes with five subthemes: fear of exacerbation (bodily
      sensations, frightening experiences, and loss of control) and fear of being
      ostracized (experiences of being excluded and dilemma of keeping the asthma
      secret or being open about it). Drawings are a good tool for initiating a
      dialogue with children.

PMID- 21726780
TI  - Engaging fathers in behavioral parent training: listening to fathers' voices.
AB  - This is a qualitative study documenting the experiences of fathers who
      participated in the Helping Our Toddlers, Developing Our Children's Skills (HOT
      DOCS) behavioral parent training (BPT) series and later agreed to participate in
      a focus group. Focus groups methodology was used to capture the voices and
      perspectives of fathers regarding the benefits and barriers to their
      participation in BPT. The focus group interviews were conducted in both English
      and in Spanish, with three cohorts of male caregivers who were participants in
      HOT DOCS from 2006 to 2008. An analysis of their responses coded from transcripts
      of the focus groups identified five major themes, which are discussed as (a)
      motivational factors for joining BPT, (b) fathers' experiences with BPT, (c)
      barriers regarding fathers' participation, (d) changes in parenting as a result
      of BPT, and (e) perceived changes in children's behavior as a result of BPT. In
      addition, recommendations for improvement of BPT are presented. This research may
      be helpful in improving efforts to engage male caregivers in BPT and thereby
      reduce children's challenging behavior problems and improve program outcomes.

PMID- 21726781
TI  - Development of an evidence-based clinical practice guideline on linear growth
      measurement of children.
AB  - Growth is an important indicator of child health; however, measurements are
      frequently inaccurate and unreliable. This article reviews the literature on
      linear growth measurement error and describes methods used to develop and
      evaluate an evidence-based clinical practice guideline on the measurement of
      recumbent length and stature of infants, children, and adolescents. Systematic
      methods were used to identify evidence to answer clinical questions about growth
      measurement. A multidisciplinary team critically appraised and synthesized the
      evidence to develop clinical practice recommendations using an evidence-based
      practice rating scheme. The guideline was prospectively evaluated through
      internal and external reviews and a pilot study to ensure its validity and
      reliability. Adoption of the clinical practice guideline can improve the accuracy
      and reliability of growth measurement data.

PMID- 21726782
TI  - Maslow's needs hierarchy as a framework for evaluating hospitality houses'
      resources and services.
AB  - As hospitality houses welcome greater numbers of families and families requiring
      longer stays, they do so in the absence of a widely accepted theory to guide
      their understanding of guests' needs and evaluations of how well they meet those
      needs. We propose A. Maslow's (1970) Hierarchy of Needs as a conceptual framework
      for understanding what makes a hospitality house a home for families of pediatric
      patients and for guiding the activities of hospitality houses' boards of
      directors, staff, volunteers, and donors. This article presents findings from a
      theory-driven evaluation of one hospitality house's ability to meet guests'
      needs, describes the house's best practice standards for addressing guests'
      needs, and suggests areas for future research.

PMID- 21726783
TI  - Understanding hospitality house guests' needs: a brief case report.
AB  - A.E. Kazak's (2006) call to develop theory-driven and empirically supported
      programs aimed at strengthening the competencies of families affected by
      pediatric illness applies to both medical and nonmedical facilities and
      institutions that care for pediatric patients and their loved ones. M.K.W. Duncan
      and A. Blugis (in press, this issue) note that despite the intuitive and
      practical nature of Maslow's Hierarchy of Needs, no theory translates into an
      infallible understanding of any individual guest's needs or a program of
      universally applied best practice standards for meeting those needs. Using
      Maslow's theory as a framework, this brief report describes the complexity and
      fluidity of one mother's needs during her stay at a hospitality house following
      the birth of her premature twin babies.

PMID- 21726784
TI  - Developmental surveillance of infants and toddlers by maternal and child health
      nurses in an Australian community-based setting: promoting the early
      identification of autism spectrum disorders.
AB  - Although signs of autism spectrum disorders (ASDs) are evident during the first
      year of life, few children are diagnosed prior to 3 years. The objective in this
      article is to highlight the role that primary health care professionals can play
      in the early identification of ASDs by briefly outlining the successful
      implementation of The Social Attention and Communication Study. Maternal and
      child health nurses were trained on the early signs of ASDs, which enabled them
      to identify these children prior to 2 years. The training procedure used will be
      outlined, and the early signs that were monitored will be explained in detail. It
      is recommended that routine monitoring for ASDs in infancy and toddlerhood become
      standard practice among all primary health care professionals.

PMID- 21726785
TI  - Developing guidelines for child health care nurses to prevent nonsynostotic
      plagiocephaly: searching for the evidence.
AB  - The aim of the project was to develop guidelines for nurses that can be
      incorporated into the Swedish child health care program to prevent nonsynostotic
      plagiocephaly in infants while still following sudden infant death syndrome
      preventive measures. Guidelines were developed by reviewing the literature,
      compiling evidence, appraising recommendations, and formulating a condensed
      version of relevant information for nurses. The guidelines were tested clinically
      in a Swedish pilot project.

PMID- 21726786
TI  - Health Fairs as a forum to pique young children's interest in nursing.
AB  - Kids into Health Career (KIHC) initiatives largely have focused on the
      recruitment of high school- and middle school-age students. Little attention has
      been given to informing young children and their parents about health professions
      careers. The career development literature supports that career development is a
      lifelong process beginning in early childhood. The purpose of this article is to
      offer practical ideas to introduce preschool-age and elementary school-age
      children to health careers in nursing. The value of health fairs as a forum to
      pique interest is discussed. Outcome measures to determine the success of KIHC
      strategies for younger children are needed.

PMID- 21726787
TI  - Consequences of the "back to sleep" program in infants.
AB  - Sudden infant death syndrome (SIDS) is the third leading cause of infant
      mortality in the United States and the leading cause of death among infants 28
      364 days of age. The "Back to Sleep" program was implemented in 1992 to promote
      supine sleeping in efforts to prevent SIDS. Along with this implementation came
      several consequences that are avoidable in infants. The purposes of this article
      are to describe the Back to Sleep program and its intended purpose, to identify
      the adverse consequences, and to develop a teaching program for nurse
      practitioners to use with parents that will both promote safe sleeping and reduce
      the untoward consequences of the back to sleep program while maintaining the
      integrity of the SIDS prevention advice.

PMID- 21726788
TI  - Best evidence: nasogastric tube placement verification.
AB  - Further research on cost-effective techniques to verify enteral tube placement is
      warranted using a variety of pediatric populations with differing conditions that
      may impact gastric pH. It is imperative that clinical facilities review current
      policies and procedures to ensure that evidence-based findings are guiding
      nursing practice. Many nurses continue to rely on auscultation to verify NGT
      placement. Education and competency validation can assist with current practices
      for NGT placement being consistently incorporated by all personnel in the health
      care setting. Continuing to search for evidence related to nursing care will
      guide the direct care RN in providing best practice.

PMID- 21726789
TI  - New screening guidelines for eating disorders.

PMID- 21726790
TI  - Nanotechnology in pediatrics: science fiction or reality?

PMID- 21726791
TI  - Research commentary-evaluating educational programs in pediatric nursing:
      translating research outcomes to improve practice.

PMID- 21726792
TI  - Effects of Echinaforce(r) treatment on ex vivo-stimulated blood cells.
AB  - The herb Echinacea purpurea, also called purple coneflower, is regarded as an
      immune modulator. This study examined changes in cytokine production in blood
      samples from 30 volunteers before and during 8-day oral administration with an
      ethanolic extract of fresh Echinacea purpurea (Echinaforce((r))). Daily blood
      samples were ex vivo stimulated by LPS/SEB or Zymosan and analysed for a series
      of cytokines and haematological and metabolic parameters. Treatment reduced the
      proinflammatory mediators TNF-alpha and IL-1beta by up to 24% (p<0.05) and
      increased anti-inflammatory IL-10 levels by 13% (p<0.05) in comparison to
      baseline. This demonstrated a substantial overall anti-inflammatory effect of
      Echinaforce((r)) for the whole group (n=28). Chemokines MCP-1 and IL-8 were
      upregulated by 15% in samples from subjects treated with Echinaforce((r))
      (p<0.05). An analysis of a subgroup of volunteers who showed low pre-treatment
      levels of the cytokines MCP-1, IL-8, IL-10 or IFN-gamma (n=8) showed significant
      stimulation of these factors upon Echinaforce((r)) treatment (30-49% increases;
      p<0.05), whereas the levels in subjects with higher pre-treatment levels remained
      unaffected. We chose the term "adapted immune-modulation" to describe this
      observation. Volunteers who reported high stress levels (n=7) and more than 2
      colds per year experienced a significant transient increase in IFN-gamma upon
      Echinaforce((r)) treatment (>50%). Subjects with low cortisol levels (n=11)
      showed significant down-regulation of the acute-phase proteins IL1-beta, IL-6, IL
      12 and TNF-alpha by Echinaforce((r)) (range, 13-25%), while subjects with higher
      cortisol levels showed no such down-regulation. This is the first ex vivo study
      to demonstrate adapted immune-modulation by an Echinacea preparation. While
      Echinaforce((r)) did not affect leukocyte counts, we speculate that the
      underlying therapeutic mechanism is based on differential multi-level modulation
      of the responses of the different types of leukocytes. Echinaforce((r)) thus
      regulates the production of chemokines and cytokines according to current immune
      status, such as responsiveness to exogenous stimuli, susceptibility to viral
      infection and exposure to stress.

PMID- 21726793
TI  - Three courses of microbes and metabolism.

PMID- 21726794
TI  - Introduction to a new series: advanced topics in evidence-based urologic
      oncology.

PMID- 21726795
TI  - Advanced topics in evidence-based urologic oncology: surrogate endpoints.
AB  - Clinical trials often report surrogate endpoint data. A surrogate endpoint is a
      biological marker or clinical sign that can be substituted for a patient
      important outcome. Using surrogate endpoints correctly may facilitate and
      expedite clinical trials and may improve medical decisions. However, rigorous
      criteria must be met for an endpoint to be considered a valid surrogate. The
      purpose of this article is to review the topic of surrogate endpoints in the
      context of a urologic encounter.

PMID- 21726796
TI  - Advanced topics in evidence-based urologic oncology: economic analysis.
AB  - Urologists, regardless of whether they practice in the community or in an
      academic institution, make decisions not only about their individual patients but
      also about hospital and health care policy by providing input to various
      committees that influence the adoption of new diagnostic and therapeutic
      technology. In an era of increasing awareness of healthcare costs, economic
      analyses that consider not only the potential benefit and harm of a given
      intervention but also the costs of the intervention, are increasingly important.
      This review article introduces a framework to critically appraise an economic
      analysis for its validity, impact, and applicability to patient care using an
      example from the urologic literature.

PMID- 21726797
TI  - Advanced topics in evidence-based urological oncology: using results of a
      subgroup analysis.
AB  - BACKGROUND: Randomized, controlled trials are the cornerstone of evaluation for
      therapies in urologic oncology. Clinicians and investigators are frequently
      interested in whether treatment effects differ among subgroups of patients
      defined by clinically relevant characteristics. METHODS: The evidence-based
      approach to subgroup analysis is explored using an example from the urologic
      literature. Potential reasons why the results of subgroup analyses may not be
      reliable are reviewed. Criteria for assessing the validity of a subgroup effect
      are described. RESULTS: The likelihood of observing clinically important
      differences in treatment results by chance increases with each additional
      comparison of groups. Ideally, subgroup comparisons should be specified a priori
      and few in number. The probability of observing the difference in outcomes due to
      chance should be low and, ideally, the difference will be large. Finally,
      external evidence or biologic data should support the hypothesized difference in
      subgroup outcomes. CONCLUSION: Use of these criteria for subgroup analyses will
      promote a more evidence-based management for oncologic diseases within urology.
      Understanding appropriate use of subgroup analyses will help clinicians target
      therapies towards those patients most likely to benefit, and avoid both limiting
      potentially beneficial therapies or utilizing ineffective therapies when observed
      subgroup treatment effects are likely due to chance.

PMID- 21726803
TI  - S-Nitrosylation at the interface of autophagy and disease.
AB  - In this issue of Molecular Cell, Sarkar et al. (2011) provide the first evidence
      for involvement of nitric oxide bioactivity in autophagy and suggest new insight
      into the role of aberrant S-nitrosylation in the pathogenesis of
      neurodegeneration.

PMID- 21726804
TI  - Reversible acetylation of metabolic enzymes celebration: SIRT2 and p300 join the
      party.
AB  - Compelling evidence suggests that metabolic pathways are coordinated through
      reversible acetylation of metabolic enzymes in response to nutrient availability.
      In this issue of Molecular Cell, Jiang et al. (2011) show that the rate-limiting
      enzyme in gluconeogenesis, phosphoenolpyruvate carboxykinase 1, is regulated
      through reversible acetylation by SIRT2 and p300.

PMID- 21726805
TI  - The United States of histone ubiquitylation and methylation.
AB  - In this issue of Molecular Cell, Wu et al. (2011) reveal that ubiquitylation of
      histone 2B lysine 34 stimulates histone methyltransferase activity on
      nucleosomes, a finding with implications for the general mechanism by which
      monoubiquitylation may influence subsequent modification activities.

PMID- 21726806
TI  - A diversity of assembly mechanisms of a generic amyloid fold.
AB  - Protein misfolding and amyloid assembly have long been recognized as being
      responsible for many devastating human diseases. Recent findings indicate that
      amyloid assemblies may facilitate crucial biological processes from bacteria to
      mammals. This review focuses on the mechanistic understanding of amyloid
      formation, including the transformation of initially innocuous proteins into
      oligomers and fibrils. The result is a competing folding and assembly energy
      landscape, which contains a number of routes by which the polypeptide chain can
      convert its primary sequence into functional structures, dysfunctional
      assemblies, or epigenetic entities that provide both threats and opportunities in
      the evolution of life.

PMID- 21726808
TI  - Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via
      recruiting the UBR5 ubiquitin ligase.
AB  - Protein acetylation has emerged as a major mechanism in regulating cellular
      metabolism. Whereas most glycolytic steps are reversible, the reaction catalyzed
      by pyruvate kinase is irreversible, and the reverse reaction requires
      phosphoenolpyruvate carboxykinase (PEPCK1) to commit for gluconeogenesis. Here,
      we show that acetylation regulates the stability of the gluconeogenic rate
      limiting enzyme PEPCK1, thereby modulating cellular response to glucose. High
      glucose destabilizes PEPCK1 by stimulating its acetylation. PEPCK1 is acetylated
      by the P300 acetyltransferase, and this acetylation stimulates the interaction
      between PEPCK1 and UBR5, a HECT domain containing E3 ubiquitin ligase, therefore
      promoting PEPCK1 ubiquitinylation and degradation. Conversely, SIRT2 deacetylates
      and stabilizes PEPCK1. These observations represent an example that acetylation
      targets a metabolic enzyme to a specific E3 ligase in response to metabolic
      condition changes. Given that increased levels of PEPCK are linked with type II
      diabetes, this study also identifies potential therapeutic targets for diabetes.

PMID- 21726807
TI  - Complex inhibitory effects of nitric oxide on autophagy.
AB  - Autophagy, a major degradation process for long-lived and aggregate-prone
      proteins, affects various human processes, such as development, immunity, cancer,
      and neurodegeneration. Several autophagy regulators have been identified in
      recent years. Here we show that nitric oxide (NO), a potent cellular messenger,
      inhibits autophagosome synthesis via a number of mechanisms. NO impairs autophagy
      by inhibiting the activity of S-nitrosylation substrates, JNK1 and IKKbeta.
      Inhibition of JNK1 by NO reduces Bcl-2 phosphorylation and increases the Bcl-2
      Beclin 1 interaction, thereby disrupting hVps34/Beclin 1 complex formation.
      Additionally, NO inhibits IKKbeta and reduces AMPK phosphorylation, leading to
      mTORC1 activation via TSC2. Overexpression of nNOS, iNOS, or eNOS impairs
      autophagosome formation primarily via the JNK1-Bcl-2 pathway. Conversely, NOS
      inhibition enhances the clearance of autophagic substrates and reduces
      neurodegeneration in models of Huntington's disease. Our data suggest that
      nitrosative stress-mediated protein aggregation in neurodegenerative diseases may
      be, in part, due to autophagy inhibition.

PMID- 21726809
TI  - SHP2 tyrosine phosphatase converts parafibromin/Cdc73 from a tumor suppressor to
      an oncogenic driver.
AB  - Deregulation of SHP2 is associated with malignant diseases as well as
      developmental disorders. Although SHP2 is required for full activation of RAS
      signaling, other potential roles in cell physiology have not been elucidated.
      Here we show that SHP2 dephosphorylates parafibromin/Cdc73, a core component of
      the RNA polymerase II-associated factor (PAF) complex. Parafibromin is known to
      act as a tumor suppressor that inhibits cyclin D1 and c-myc by recruiting SUV39H1
      histone methyltransferase. However, parafibromin can also act in the opposing
      direction by binding beta-catenin, thereby activating promitogenic/oncogenic Wnt
      signaling. We found that, on tyrosine dephosphorylation by SHP2, parafibromin
      acquires the ability to stably bind beta-catenin. The parafibromin/beta-catenin
      interaction overrides parafibromin/SUV39H1-mediated transrepression and induces
      expression of Wnt target genes, including cyclin D1 and c-myc. Hence, SHP2
      governs the opposing functions of parafibromin, deregulation of which may cause
      the development of tumors or developmental malformations.

PMID- 21726810
TI  - Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop.
AB  - Caspase-2 is an evolutionarily conserved caspase, yet its biological function and
      cleavage targets are poorly understood. Caspase-2 is activated by the p53 target
      gene product PIDD (also known as LRDD) in a complex called the Caspase-2
      PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy
      resistance by a mechanism that depends on Caspase-2 and wild-type p53. PIDD
      induced Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367,
      leading to loss of the C-terminal RING domain responsible for p53 ubiquitination.
      As a consequence, N-terminally truncated Mdm2 binds p53 and promotes its
      stability. Upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a
      positive feedback loop that inhibits Mdm2 and reinforces p53 stability and
      activity, contributing to cell survival and drug resistance. These data establish
      Mdm2 as a cleavage target of Caspase-2 and provide insight into a mechanism of
      Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress.

PMID- 21726812
TI  - Recruitment of TIF1gamma to chromatin via its PHD finger-bromodomain activates
      its ubiquitin ligase and transcriptional repressor activities.
AB  - The interplay between sequence-specific DNA-binding transcription factors,
      histone-modifying enzymes, and chromatin-remodeling enzymes underpins
      transcriptional regulation. Although it is known how single domains of chromatin
      "readers" bind specific histone modifications, how combinations of histone marks
      are recognized and decoded is poorly understood. Moreover, the role of histone
      binding in regulating the enzymatic activity of chromatin readers is not known.
      Here we focus on the TGF-beta superfamily transcriptional repressor
      TIF1gamma/TRIM33/Ectodermin and demonstrate that its PHD finger-bromodomain
      constitutes a multivalent histone-binding module that specifically binds histone
      H3 tails unmethylated at K4 and R2 and acetylated at two key lysines. TIF1gamma's
      ability to ubiquitinate its substrate Smad4 requires its PHD finger-bromodomain,
      as does its transcriptional repressor activity. Most importantly, TIF1gamma's E3
      ubiquitin ligase activity is induced by histone binding. We propose a model of
      TIF1gamma activity in which it dictates the residence time of activated Smad
      complexes at promoters of TGF-beta superfamily target genes.

PMID- 21726811
TI  - Opposing effects of glutamine and asparagine govern prion formation by
      intrinsically disordered proteins.
AB  - Sequences rich in glutamine (Q) and asparagine (N) residues often fail to fold at
      the monomer level. This, coupled to their unusual hydrogen-bonding abilities,
      provides the driving force to switch between disordered monomers and amyloids.
      Such transitions govern processes as diverse as human protein-folding diseases,
      bacterial biofilm assembly, and the inheritance of yeast prions (protein-based
      genetic elements). A systematic survey of prion-forming domains suggested that Q
      and N residues have distinct effects on amyloid formation. Here, we use cell
      biological, biochemical, and computational techniques to compare Q/N-rich protein
      variants, replacing Ns with Qs and Qs with Ns. We find that the two residues have
      strong and opposing effects: N richness promotes assembly of benign self
      templating amyloids; Q richness promotes formation of toxic nonamyloid
      conformers. Molecular simulations focusing on intrinsic folding differences
      between Qs and Ns suggest that their different behaviors are due to the enhanced
      turn-forming propensity of Ns over Qs.

PMID- 21726814
TI  - siRNA repositioning for guide strand selection by human Dicer complexes.
AB  - The human ribonuclease Dicer and its double-stranded RNA (dsRNA)-binding protein
      (dsRBP) partners TRBP and PACT play important roles in the biogenesis of
      regulatory RNAs. Following dicing, one dsRNA product strand is preferentially
      assembled into an RNA-induced silencing complex (RISC). The mechanism of strand
      selection in humans and the possible role of Dicer in this process remain
      unclear. Here we demonstrate that dsRNAs undergo significant repositioning within
      Dicer complexes following dicing. This repositioning enables directional binding
      of RNA duplexes, thereby biasing their orientation for guide strand selection
      according to the thermodynamic properties of the helix. Our findings indicate
      that Dicer is itself capable of sensing siRNA thermodynamic asymmetry regardless
      of the dsRBP to which it is bound. These results support a model in which Dicer
      employs two distinct RNA-binding sites-one for dsRNA processing and the other for
      sensing of siRNA thermodynamic asymmetry-during RISC loading in humans.

PMID- 21726813
TI  - Mammalian hyperplastic discs homolog EDD regulates miRNA-mediated gene silencing.
AB  - MicroRNAs (miRNAs) regulate gene expression through translation repression and
      mRNA destabilization. However, the molecular mechanisms of miRNA silencing are
      still not well defined. Using a genetic screen in mouse embryonic stem (ES)
      cells, we identify mammalian hyperplastic discs protein EDD, a known E3 ubiquitin
      ligase, as a key component of the miRNA silencing pathway. ES cells deficient for
      EDD are defective in miRNA function and exhibit growth defects. We demonstrate
      that E3 ubiquitin ligase activity is dispensable for EDD function in miRNA
      silencing. Instead, EDD interacts with GW182 family proteins in the Argonaute
      miRNA complexes. The PABC domain of EDD is essential for its silencing function.
      Through the PABC domain, EDD participates in miRNA silencing by recruiting
      downstream effectors. Among the PABC-interactors, DDX6 and Tob1/2 are both
      required and sufficient for silencing mRNA targets. Taken together, these data
      demonstrate a critical function for EDD in miRNA silencing.

PMID- 21726815
TI  - Failure of origin activation in response to fork stalling leads to chromosomal
      instability at fragile sites.
AB  - Perturbed DNA replication in early stages of cancer development induces
      chromosomal instability preferentially at fragile sites. However, the molecular
      basis for this instability is unknown. Here, we show that even under normal
      growth conditions, replication fork progression along the fragile site, FRA16C,
      is slow and forks frequently stall at AT-rich sequences, leading to activation of
      additional origins to enable replication completion. Under mild replication
      stress, the frequency of stalling at AT-rich sequences is further increased.
      Strikingly, unlike in the entire genome, in the FRA16C region additional origins
      are not activated, suggesting that all potential origins are already activated
      under normal conditions. Thus, the basis for FRA16C fragility is replication fork
      stalling at AT-rich sequences and inability to activate additional origins under
      replication stress. Our results provide a mechanism explaining the replication
      stress sensitivity of fragile sites and thus, the basis for genomic instability
      during early stages of cancer development.

PMID- 21726816
TI  - The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B
      K34 and is involved in crosstalk with H3 K4 and K79 methylation.
AB  - We demonstrate that RING finger protein MSL2 in the MOF-MSL complex is a histone
      ubiquitin E3 ligase. MSL2, together with MSL1, has robust histone ubiquitylation
      activity that mainly targets nucleosomal H2B on lysine 34 (H2B K34ub), a site
      within a conserved basic patch on H2B tail. H2B K34ub by MSL1/2 directly
      regulates H3 K4 and K79 methylation through trans-tail crosstalk both in vitro
      and in cells. The significance of MSL1/2-mediated histone H2B ubiquitylation is
      underscored by the facts that MSL1/2 activity is important for transcription
      activation at HOXA9 and MEIS1 loci and that this activity is evolutionarily
      conserved in the Drosophila dosage compensation complex. Altogether, these
      results indicate that the MOF-MSL complex possesses two distinct chromatin
      modifying activities (i.e., H4 K16 acetylation and H2B K34 ubiquitylation)
      through MOF and MSL2 subunits. They also shed light on how an intricate network
      of chromatin-modifying enzymes functions coordinately in gene activation.

PMID- 21726818
TI  - Comorbidity in lung cancer: important but neglected. a review of the current
      literature.
AB  - INTRODUCTION: Treatment and survival rates for patients with lung cancer in
      Scotland appear lower than in many other European countries. Five-year survival
      is quoted at 6% to 7% compared with 8% to 15% in other European countries and
      America. There also appear to be variations in treatment rates within Scotland.
      Although this variation in treatment and survival is popularly interpreted as
      evidence of variation in facilities, access to care, and clinical practice, it is
      possible that the increased comorbidity and poor performance status of the
      Scottish population may contribute to the observed disparities in treatment and
      outcomes, although this has never been proven. The demonstration that comorbidity
      influences treatment and survival rates will have important implications for the
      targeting of health services resources, screening, interpretation of cancer
      statistics, and the assessment and management of patients with lung cancer.
      METHODS: In this article we have reviewed the tools currently available for
      assessing comorbidity and in addition have identified published works which study
      the effect of comorbidity in lung cancer. CONCLUSION: There is no currently
      validated measurement tool applicable specifically to lung cancer and thus there
      remains a significant need for further work in this important area. STATEMENT OF
      SEARCH STRATEGIES USED AND SOURCES OF INFORMATION: Literature searches were
      undertaken via PubMed and Google Scholar using various arrays of the following
      keywords: cancer, comorbidity, lung lancer, performance status, survival, and
      tools. The search was limited to articles published in peer-review journals with
      English as the language.

PMID- 21726817
TI  - Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid
      receptor binding.
AB  - Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor
      (GR) is mediated by interactions with coregulators. The role of these
      interactions in determining selective binding of GR to regulatory elements
      remains unclear. Recent findings indicate that a large fraction of genomic GR
      binding coincides with chromatin that is accessible prior to hormone treatment,
      suggesting that receptor binding is dictated by proteins that maintain chromatin
      in an open state. Combining DNaseI accessibility and chromatin
      immunoprecipitation with high-throughput sequencing, we identify the activator
      protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1
      is critical for GR-regulated transcription and recruitment to co-occupied
      regulatory elements, illustrating an extensive AP1-GR interaction network.
      Importantly, the maintenance of baseline chromatin accessibility facilitates GR
      recruitment and is dependent on AP1 binding. We propose a model in which the
      basal occupancy of transcription factors acts to prime chromatin and direct
      inducible transcription factors to select regions in the genome.

PMID- 21726819
TI  - Long-term safety and tolerability of sorafenib in patients with advanced non
      small-cell lung cancer: a case-based review.
AB  - BACKGROUND: Sorafenib, a small-molecule inhibitor of multiple kinases involved in
      tumor growth and progression, is approved for the treatment of advanced renal
      cell carcinoma and advanced hepatocellular carcinoma. Encouraging activity and
      good tolerability of daily oral sorafenib, either as a single agent or in
      combination with gefitinib, have been demonstrated in phase I-II trials in
      patients with advanced non-small-cell lung cancer (NSCLC). Currently, minimal
      data are available describing the long-term safety and tolerability of sorafenib
      in patients with NSCLC. MATERIALS AND METHODS: We describe a series of 12
      patients with advanced NSCLC (derived from 1 phase I and 2 phase II trials) who
      achieved long-term (ie, > 12 months) disease control and continued to receive
      sorafenib alone or in combination with gefitinib beyond the end of the study in
      which they were enrolled. RESULTS: The safety profile of sorafenib administered
      on a long-term basis did not differ significantly from that seen previously in
      the shorter term. The majority of adverse events (AEs) were Grade 1-2 in
      severity. Five of the 12 patients experienced no >= Grade 3 AEs. There was no
      evidence of increased frequency or severity of AEs over time, or of late AEs, and
      no patient in this series discontinued study treatment because of AEs.
      CONCLUSION: In patients with advanced NSCLC who achieve a prolonged response or
      stable disease with sorafenib given as a single agent or as part of a combination
      regimen, sorafenib treatment could be continued until disease progression without
      major long-term safety or tolerability problems.

PMID- 21726820
TI  - Analysis of lung cancer patients enrolled in CTEP (cancer therapy evaluation
      program)-sponsored phase I trials.
AB  - INTRODUCTION: A recent review of phase I trials suggests that participation in
      these trials can be associated with clinical benefit and the rate of drug-related
      deaths is low. We conducted an analysis of the Cancer Therapy Evaluation Program
      (CTEP)-sponsored phase I trials to assess the outcomes of lung cancer patients
      enrolled in phase I trials. MATERIALS AND METHODS: Data from all CTEP-sponsored
      adult phase I trials conducted between 1997 and 2008 were analyzed. An analysis
      of demographics, rates of toxicities, and clinical benefit rate among patients
      with non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and other
      cancers was conducted. RESULTS: Of the 3560 patients enrolled in 136 phase I
      trials, 301 (8.5%) had NSCLC and 40 (1.1%) had SCLC. The median age of lung
      cancer patients, at 60 years, was significantly higher than patients with other
      cancers. The rest of the demographics were similar among the groups. The rate of
      Grade 3-5 toxicities was higher among NSCLC patients (54% versus 46%). The
      toxicity-related death rate was <= 1% among all groups. The clinical benefit rate
      and median duration in study of approximately 2 months were similar among all
      groups of patients. CONCLUSION: An analysis of the CTEP-sponsored phase I trials
      shows that lung cancer patients enrolled in these trials have a similar incidence
      of toxicity-related deaths and a similar probability of clinical benefit as
      patients with other cancers. These data suggest that patients with progressive
      lung cancer following approved therapies should be considered for phase I trials.

PMID- 21726821
TI  - Chemotherapy-induced neutropenia does not correlate with DNA repair gene
      polymorphisms and treatment efficacy in advanced non-small-cell lung cancer
      patients.
AB  - BACKGROUND: Platinum doublets are standard chemotherapy for advanced non-small
      cell lung cancer (NSCLC). The aim of this study was to assess whether neutropenia
      is: (1) an indicator for treatment efficacy, or (2) associated with specific
      polymorphisms. PATIENTS AND METHODS: Four hundred ninety-four patients, treated
      with cisplatin-docetaxel were retrospectively analyzed. Relative dose intensity
      (RDI) was assessed for both drugs. Neutrophil counts were assessed only on Day 21
      of each cycle. Genotyping was performed for 4 different polymorphisms in ERCC1,
      XRCC3, XPD-23, and XPD-10. RESULTS: The median overall survival was 9 months. The
      mean RDI was 0.94 for cisplatin and 0.93 for docetaxel. Four hundred three
      patients received >= 3 cycles of chemotherapy, and 239 received >= 6 cycles.
      Thirty-one percent developed neutropenia, and 19% had Grade (G)3-4 neutropenia.
      RDI was lower in patients with neutropenia (G1-4; 0.87-0.93) when compared with
      those without (G0; 0.94-0.95; P < .02). Male patients (P = .02) had inferior
      survival when compared with female patients, and ECOG (Eastern Cooperative
      Oncology Group) 1-2 patients (P < .001) had worse survival when compared with
      ECOG 0. There was no significant survival difference with respect to Grade of
      neutropenia (G0, 8.7 vs. G1-2, 11.6 vs. G3-4, 9.6 months; P = .41). In ECOG 0
      patients, survival was significantly better for neutropenic G1-4 (hazard ratio
      [HR], 0.55; 95% confidence interval [CI], 0.31-0.96; P = .034) when compared with
      non-neutropenic (G0) patients. No association was observed between examined
      polymorphisms and neutropenia. CONCLUSION: RDI was significantly higher in
      patients who did not develop neutropenia during treatment, but as the nadir
      period was not explored in our study, the low occurrence of neutropenia in our
      cohort is considered underestimated. There was no significant survival difference
      with respect to grade of neutropenia. Finally, none of the examined single
      nucleotide polymorphisms (SNPs) were associated with the presence of neutropenia,
      disease characteristics, response rates, or survival.

PMID- 21726822
TI  - A phase I trial of bexarotene in combination with docetaxel in patients with
      advanced solid tumors.
AB  - BACKGROUND: The purpose of this study was to identify dose-limiting toxicity
      (DLT) and maximum tolerated dose (MTD) of docetaxel with a fixed-dose of
      bexarotene. PATIENTS AND METHODS: This was a phase I, single-center and open
      label trial of dose-escalating docetaxel with a fixed-dose oral bexarotene.
      Successive cohorts of 3 patients (pts), with confirmed solid tumors refractory to
      standard therapy or for whom no standard therapy existed, received fixed-dose
      oral bexarotene (400 mg/m(2) daily) with escalating doses of docetaxel weekly
      (25, 30, or 35 mg/m(2)) for 3 weeks on a 4-week cycle. Cohorts were expanded to 6
      pts if a DLT was noted. The MTD was determined based on the occurrence of DLT in
      at least 2 of 6 pts during the first cycle. RESULTS: Nineteen pts were enrolled.
      Seven pts were treated at 25 mg/m(2), 6 at 30 mg/m(2), and 6 at 35 mg/m(2) of
      docetaxel. The MTD for docetaxel was 30 mg/m(2) with 400 mg/m(2) of daily
      bexarotene. Hypothyroidism, hypertriglyceridemia, and fatigue were common
      toxicities. Three pts developed pulmonary toxicity (possible radiation recall
      pneumonitis [n = 2] and pulmonary hypertension because of tumor emboli [n = 1]).
      Two pts withdrew consent because of Grade 3 fatigue. Ten of 19 pts were noted to
      have stable disease and received more than 2 cycles of therapy. Of the 10 pts
      with stable disease, 5 had non-small-cell lung cancer (NSCLC), and of those 5
      pts, 1 had a partial response that persisted for eight cycles. conclusion: The
      MTD of docetaxel was 30 mg/m(2) in combination with daily bexarotene at
      400mg/m(2). Careful monitoring may be indicated in pts with previously irradiated
      lung tumors.

PMID- 21726824
TI  - Acute esophagitis and late lung toxicity in concurrent chemoradiotherapy trials
      in patients with locally advanced non-small-cell lung cancer: analysis of the
      radiation therapy oncology group (RTOG) database.
AB  - BACKGROUND: We analyzed time course and factors associated with acute esophagitis
      (ES) and late lung toxicity (PN), as well as any association between ES and PN in
      patients (pts) with non-small-cell lung cancer (NSCLC) treated with concurrent
      chemoradiation (chemo-RT) on the Radiation Therapy Oncology Group (RTOG) trials.
      MATERIALS AND METHODS: Multivariable analysis was used to investigate factors
      associated with ES or PN. RESULTS: Patients (n = 528) received standard
      fractionated (SFX; 63 Gy) or hyperfractionated (HFX; 69.6 Gy) radiation therapy
      (RT) with cisplatin-based chemotherapy. Grade > 2 ES developed in 75% of pts;
      Grade > 3 ES, in 34%. Nineteen percent of pts developed ES by the first, 32% by
      the second, and 33% by the third month (and for Grade > 3 PN, 9% by 6 months, 15%
      by year 1, and 18% by year 2). Any PN developed in 59% of pts; Grade > 2, in 39%;
      Grade > 3, in 18%; and lethal PN, in 2%. Grade > 2 PN was associated with
      increasing RT dose and Grade > 3 PN, with HFX RT. No association was seen with
      ES. Grade > 3 ES was less likely to occur in non-whites and more likely, in pts
      treated with HFX RT. CONCLUSION: Most (95%) pts developed ES, and 33% had severe
      ES, peaking within the first or second month of RT. PN developed in 57% of pts,
      with 18% experiencing Grade > 3 PN, with most diagnosed by 1 year from RT. No
      relationship was observed between 1 toxicity (ES or PN) as predictor of the
      other. HFX RT was associated with more severe PN or ES.

PMID- 21726823
TI  - Downregulation of EMX2 is associated with clinical outcomes in lung
      adenocarcinoma patients.
AB  - BACKGROUND: The 5-year survival rate for stage I non-small-cell lung cancer
      (NSCLC) of 50% to 70% indicates that our current staging methods do not
      adequately predict outcome. Empty spiracles homeobox 2 (EMX2) is a homeo-domain
      containing transcription factor that regulates a key developmental pathway known
      to promote lung tumorigenesis. This study assessed the significance of EMX2 as a
      prognostic biomarker in lung adenocarcinoma including bronchioloalveolar
      carcinoma (BAC). PATIENTS AND METHODS: 144 patients with lung adenocarcinoma
      undergoing surgical resection were studied. Quantitative real-time reverse
      transcriptase polymerase chain reaction and Immunohistochemistry were used to
      analyze EMX2 mRNA and protein expression, respectively. Association of EMX2 mRNA
      expression levels with clinical outcomes was evaluated using the Kaplan-Meier
      method and a multivariate Cox proportional hazards regression model. RESULTS:
      EMX2 mRNA expression was significantly downregulated in lung adenocarcinoma
      compared with matched adjacent normal tissue (P < .001). EMX2 protein expression
      was similarly found to be downregulated in lung adenocarcinoma. The EMX2-high
      mRNA expressing group had statistically significant better overall survival (OS)
      than the EMX2-low mRNA expressing group (P = .005). Subgroup analysis also
      demonstrated improved survival in stage I patients (P = .01) and patients with
      BAC (P = .03). Lastly, the EMX2-high mRNA expressing group had statistically
      significant better recurrence-free survival (RFS) than the EMX2-low mRNA
      expression group in patients with adenocarcinoma (P < .001). CONCLUSION: EMX2
      expression is downregulated in lung adenocarcinoma. Low EMX2 mRNA expression is
      significantly associated with decreased OS and RFS in patients with lung
      adenocarcinoma, particularly with stage I disease and BAC.

PMID- 21726826
TI  - Wnt to notch relay signaling induces definitive hematopoiesis.
AB  - The molecular mechanisms specifying hematopoietic stem cells (HSCs) in the
      vertebrate embryo remain poorly understood. Recently in Nature, Traver and
      colleagues demonstrate that timed wnt to Notch relay signaling across multiple
      cell types serves as an early upstream mechanism of HSC induction in zebrafish
      (Clements et al., 2011).

PMID- 21726825
TI  - Proton radiation therapy offers reduced normal lung and bone marrow exposure for
      patients receiving dose-escalated radiation therapy for unresectable stage iii
      non-small-cell lung cancer: a dosimetric study.
AB  - INTRODUCTION: The purpose of this study was to determine the potential benefit of
      proton radiation therapy over photon radiation therapy in patients with
      unresectable stage III non-small-cell lung cancer. MATERIALS AND METHODS:
      Optimized 3-dimensional conformal photon (3DCRT), intensity-modulated radiation
      therapy (IMRT) and proton therapy (PT) plans were generated for 8 consecutive
      patients with unresectable stage III non-small-cell lung cancer using the same
      target goals and normal tissue constraints. The radiation exposure to non
      targeted normal structures, including lung, bone marrow, esophagus, heart, and
      spinal cord, were compared. Photon doses are expressed in gray (Gy). Proton doses
      are expressed in cobalt gray equivalents (CGE). RESULTS: In all patients, 3DCRT,
      IMRT, and PT plans, achieved the dose goals for the target volumes. Compared with
      the 3DCRT plans, proton plans offered a median 29% reduction in normal lung V(20)
      Gy (CGE), a median 33% reduction in mean lung dose (MLD), and a median 30%
      reduction in the volume of bone marrow receiving a dose of 10 Gy (CGE). Compared
      with the IMRT plans, the proton plans offered a median 26% reduction in normal
      lung V(20) Gy (CGE), a median 31% reduction in MLD, and a median 27% reduction in
      the volume of bone marrow receiving a dose of 10 Gy (CGE). CONCLUSION: By
      reducing the volumes of normal structures irradiated, protons can potentially
      improve the therapeutic index for patients with unresectable stage III non-small
      cell lung cancer receiving combined radiation therapy and chemotherapy.

PMID- 21726827
TI  - Pluripotency without Max.
AB  - Myc/Max complexes are thought to be essential for maintaining pluripotency and
      self-renewal of embryonic stem cells (ESCs). In this issue of Cell Stem Cell,
      Hishida et al. (2011) provide genetic evidence that this requirement can be
      bypassed in well-defined culture conditions.

PMID- 21726828
TI  - Funding translational work in cell-based therapy.
AB  - The cell therapy branch of the regenerative medicine field has been innovative in
      developing new models of delivery and development and identifying alternative
      sources of funding. We discuss the implications of these changes for
      pharmaceutical companies and the opportunities they offer to a new entrepreneur.

PMID- 21726829
TI  - The MSC: an injury drugstore.
AB  - Now that mesenchymal stem cells (MSCs) have been shown to be perivascular in
      vivo, the existing traditional view that focuses on the multipotent
      differentiation capacity of these cells should be expanded to include their
      equally interesting role as cellular modulators that brings them into a broader
      therapeutic scenario. We discuss existing evidence that leads us to propose that
      during local injury, MSCs are released from their perivascular location, become
      activated, and establish a regenerative microenvironment by secreting bioactive
      molecules and regulating the local immune response. These trophic and
      immunomodulatory activities suggest that MSCs may serve as site-regulated
      "drugstores" in vivo.

PMID- 21726830
TI  - Epigenetic memory and preferential lineage-specific differentiation in induced
      pluripotent stem cells derived from human pancreatic islet beta cells.
AB  - Human induced pluripotent stem cells (HiPSCs) appear to be highly similar to
      human embryonic stem cells (HESCs). Using two genetic lineage-tracing systems, we
      demonstrate the generation of iPSC lines from human pancreatic islet beta cells.
      These reprogrammed cells acquired markers of pluripotent cells and differentiated
      into the three embryonic germ layers. However, the beta cell-derived iPSCs
      (BiPSCs) maintained open chromatin structure at key beta-cell genes, together
      with a unique DNA methylation signature that distinguishes them from other PSCs.
      BiPSCs also demonstrated an increased ability to differentiate into insulin
      producing cells both in vitro and in vivo, compared with ESCs and isogenic non
      beta iPSCs. Our results suggest that the epigenetic memory may predispose BiPSCs
      to differentiate more readily into insulin producing cells. These findings
      demonstrate that HiPSC phenotype may be influenced by their cells of origin, and
      suggest that their skewed differentiation potential may be advantageous for cell
      replacement therapy.

PMID- 21726831
TI  - Cell fate potential of human pluripotent stem cells is encoded by histone
      modifications.
AB  - Human embryonic stem cells (hESCs) expressing pluripotency markers are assumed to
      possess equipotent developmental potential. However, disparate responses to
      differentiation stimuli functionally illustrate that hESCs generate a spectrum of
      differentiated cell types, suggestive of lineage bias. Here, we reveal specific
      cell surface markers that allow subfractionation of hESCs expressing hallmark
      markers of pluripotency. By direct de novo isolation of these subsets, we
      demonstrate that propensities for lineage differentiation are balanced with
      reduced clonogenic self-renewal. Histone modification marks of gene loci
      associated with pluripotency versus lineage specificity predicted cell fate
      potential of these subfractions, thereby supporting the absence of uniform
      bivalency as a molecular paradigm to describe cell fate determination of
      pluripotent cells. Our study reveals that cell fate potential is encoded within
      cells comprising hESC cultures, highlighting them as a means to understand the
      mechanisms of lineage specification of pluripotent cells.

PMID- 21726832
TI  - Indefinite self-renewal of ESCs through Myc/Max transcriptional complex
      independent mechanisms.
AB  - Embryonic stem cells (ESCs) can self-renew indefinitely under the governance of
      ESC-specific transcriptional circuitries in which each transcriptional factor
      regulates distinct or overlapping sets of genes with other factors. c-Myc is a
      key player that is crucially involved in maintaining the undifferentiated state
      and the self-renewal of ESCs. However, the mechanism by which c-Myc helps
      preserve the ESC status is still poorly understood. Here we addressed this
      question by performing loss-of-function studies with the Max gene, which encodes
      the best-characterized partner protein for all Myc family proteins. Although
      Myc/Max complexes are widely regarded as crucial regulators of the ESC status,
      our data revealed that ESCs do not absolutely require these complexes in certain
      contexts and that this requirement is restricted to empirical ESC culture
      conditions without a MAPK inhibitor.

PMID- 21726833
TI  - CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation
      through STAT3-mediated NANOG regulation.
AB  - Tumor-initiating cells (T-ICs) are a subpopulation of chemoresistant tumor cells
      that have been shown to cause tumor recurrence upon chemotherapy. Identification
      of T-ICs and their related pathways are therefore priorities for the development
      of new therapeutic paradigms. We established chemoresistant hepatocellular
      carcinoma (HCC) xenograft tumors in immunocompromised mice in which an enriched T
      IC population was capable of tumor initiation and self-renewal. With this model,
      we found CD24 to be upregulated in residual chemoresistant tumors when compared
      with bulk tumor upon cisplatin treatment. CD24(+) HCC cells were found to be
      critical for the maintenance, self-renewal, differentiation, and metastasis of
      tumors and to significantly impact patients' clinical outcome. With a lentiviral
      based knockdown approach, CD24 was found to be a functional liver T-IC marker
      that drives T-IC genesis through STAT3-mediated NANOG regulation. Our findings
      point to a CD24 cascade in liver T-ICs that may provide an attractive therapeutic
      target for HCC patients.

PMID- 21726835
TI  - Enhanced perception of various linguistic features by musicians: a cross
      linguistic study.
AB  - Two cross-linguistic experiments comparing musicians and non-musicians were
      performed in order to examine whether musicians have enhanced perception of
      specific acoustical features of speech in a second language (L2). These
      discrimination and identification experiments examined the perception of various
      speech features; namely, the timing and quality of Japanese consonants, and the
      quality of Dutch vowels. We found that musical experience was more strongly
      associated with discrimination performance rather than identification
      performance. The enhanced perception was observed not only with respect to L2,
      but also L1. It was most pronounced when tested with Japanese consonant timing.
      These findings suggest the following: 1) musicians exhibit enhanced early
      acoustical analysis of speech, 2) musical training does not equally enhance the
      perception of all acoustic features automatically, and 3) musicians may enjoy an
      advantage in the perception of acoustical features that are important in both
      language and music, such as pitch and timing.

PMID- 21726834
TI  - All hematopoietic cells develop from hematopoietic stem cells through Flk2/Flt3
      positive progenitor cells.
AB  - While it is clear that a single hematopoietic stem cell (HSC) is capable of
      giving rise to all other hematopoietic cell types, the differentiation paths
      beyond HSC remain controversial. Contradictory reports on the lineage potential
      of progenitor populations have questioned their physiological contribution of
      progenitor populations to multilineage differentiation. Here, we established a
      lineage tracing mouse model that enabled direct assessment of differentiation
      pathways in vivo. We provide definitive evidence that differentiation into all
      hematopoietic lineages, including megakaryocyte/erythroid cell types, involves
      Flk2-expressing non-self-renewing progenitors. A Flk2+ stage was used during
      steady-state hematopoiesis, after irradiation-induced stress and upon HSC
      transplantation. In contrast, HSC origin and maintenance do not include a Flk2+
      stage. These data demonstrate that HSC specification and maintenance are Flk2
      independent, and that hematopoietic lineage separation occurs downstream of Flk2
      upregulation.

PMID- 21726836
TI  - Comparison of differential expression of P2Y12 receptor in culprit coronary
      plaques in patients with acute myocardial infarction versus stable angina
      pectoris.
AB  - P2Y12 receptor antagonists may have pleiotropic benefits. Little is known,
      however, about the expression of P2Y12 receptors in coronary atherosclerotic
      plaques. We investigated the expression of P2Y12 receptor in coronary atherectomy
      tissues retrieved from patients with acute myocardial infarction (AMI) or stable
      angina pectoris (SAP). Tissue specimens were collected from 35 patients with AMI
      and 19 with SAP who underwent directional coronary atherectomy. Specimens were
      analyzed immunohistochemically using antibodies specific to P2Y12 receptor and to
      markers of endothelial cells, macrophages, and smooth muscle cells. The 2 groups
      had similar baseline clinical characteristics. Plaque types were more likely to
      be cellular in the AMI group. The proportion of areas immunopositive for alpha
      smooth muscle actin was smaller but those positive for CD31 and CD68 were larger
      in the AMI than in the SAP group. In addition, the relative area immunopositive
      for P2Y12 receptor was significantly larger for AMI than SAP (1.1 +/- 0.9% vs 0.5
      +/- 0.4%, respectively, p < 0.001). P2Y12 receptor positivity coincided with
      areas positive for CD31 and alpha-smooth muscle actin. In conclusion, P2Y12
      receptor is present in coronary atherosclerotic plaques and is increased in
      culprit plaques of patients with AMI. P2Y12 receptor may play a role in plaque
      destabilization.

PMID- 21726837
TI  - Comparison of efficacy and safety of a standard versus a loading dose of
      clopidogrel for acute myocardial infarction in patients >= 75 years of age (from
      the FAST-MI registry).
AB  - Data are lacking on the efficacy and safety of a loading dose (LD) of clopidogrel
      in elderly patients with acute myocardial infarction (AMI). FAST-MI is a
      nationwide registry that was carried out over a 1-month period in 2005 and
      included consecutive patients with AMI admitted to intensive care units <48 hours
      from symptom onset in 223 participating centers. We assessed the impact of a
      clopidogrel LD (>=300 mg) compared to a conventional dose (<300 mg) on bleeding,
      need for blood transfusion, and 30-day and 12-month survivals in 791 elderly
      patients (>=75 years old, mean age 81 +/- 4 years, 48% women, 35% with ST-segment
      elevation MI) included in this registry. Fifty-nine percent (466 patients)
      received a clopidogrel LD. Follow-up was >99% complete. Major bleeding and blood
      transfusions were not significantly different in patients who received a
      clopidogrel LD (3.2% vs 3.7%, p = 0.72; 5.4% vs 6.2%, p = 0.64, respectively).
      Early mortality was also not significantly different (10.1 vs 10.8, p = 0.76).
      Using multivariate analyses, clopidogrel LD did not significantly affect major
      bleeding or transfusion (odds ratio 1.03, 95% confidence interval 0.49 to 2.17, p
      = 0.94) and 12-month mortality (hazard ratio 1.00, 95% confidence interval 0.72
      to 1.40, p = 0.98). In conclusion, the present data showed that in elderly
      patients admitted for AMI, use of a LD of clopidogrel compared to a conventional
      dose was not associated with increased in-hospital bleeding, need for
      transfusion, or mortality. Large-scale randomized trials are still needed to
      identify the optimal LD of clopidogrel for elderly patients admitted for AMI.

PMID- 21726838
TI  - Diagnosing acute myocardial infarction in patients with left bundle branch block.
AB  - We compared the clinical features, laboratory and coronary angiographic findings,
      treatments, and outcomes among patients with ST-segment elevation myocardial
      infarction (MI) with and without left bundle branch block (LBBB). We examined
      5,742 patients with ST-segment elevation MI with and without LBBB treated with
      primary percutaneous coronary intervention in the Assessment of Pexelizumab in
      Acute Myocardial Infarction trial. The main outcome measures were obstructive
      coronary disease, MI, positive cardiac biomarkers, angiographic Thrombolysis In
      Myocardial Infarction flow, and death, MI, or congestive heart failure at 90
      days. LBBB was present in 98 patients (1.7%). According to the protocol, patients
      with LBBB were eligible only if they had >=1 mm concordant ST-segment elevation.
      Obstructive coronary artery disease was present in >87% of the patients with
      LBBB. Documented MI (elevated biomarkers) with an initially occluded infarct
      artery was more common in patients with LBBB with concordant ST-segment elevation
      (71.4%) than in patients without (44.1%; p = 0.027). The use of ST-segment
      elevation concordance criteria in the presence of LBBB was more often associated
      with documented MI with an identifiable culprit vessel with an initially occluded
      infarct-related artery. In conclusion, because a substantial proportion of
      patients with LBBB have acute MI with a culprit lesion and positive biomarkers,
      these data support immediate catheterization with the intent for primary
      percutaneous coronary intervention for all patients presenting with suspected ST
      segment elevation myocardial infarction, ischemic symptoms, and presumed new
      LBBB, particularly if concordant ST-segment elevation is present.

PMID- 21726839
TI  - Percutaneous double-valve interventions for aortic stenosis and pure mitral
      regurgitation.
AB  - Percutaneous interventions for valvular heart disease are rapidly gaining
      momentum. Transcatheter aortic valve implantation for aortic stenosis in patients
      with high surgical risk and percutaneous mitral valve repair with the MitraClip
      have been shown to be noninferior to surgery. Little is known about the
      combination of these interventions in patients with mixed valvular disease. The
      investigators present 2 patients, both with acute device successes but
      contrasting outcomes, and attempt to glean some insights from these patients.

PMID- 21726840
TI  - Comparison of gender-specific mortality in patients < 70 years versus >= 70 years
      old with acute myocardial infarction.
AB  - The aim of the present study was to investigate the gender-specific mortality
      after acute myocardial infarction in those aged < 70 years versus >= 70 years.
      The present study consisted of 2,677 consecutive patients with acute myocardial
      infarction who had undergone coronary angiography within 24 hours after the onset
      of symptoms. The patients were divided into 2 groups: 1,810 patients < 70 years
      old and 867 patients >= 70 years old. Women were older and had a greater
      incidence of hypertension and diabetes mellitus and a lower incidence of current
      smoking and previous myocardial infarction in both groups. The in-hospital
      mortality rate was significantly greater in women >= 70 years old age than in men
      >= 70 years old (16.2% vs 9.3%, respectively; p = 0.003) but was comparable
      between women and men in patients < 70 years old (5.7% vs 4.9%, respectively; p =
      0.59). On multivariate analysis, the association between female gender and in
      hospital mortality in patients >= 70 years old remained significant (odds ratio
      1.78, 95% confidential interval 1.05 to 3.00), but the gender difference was not
      observed in patients < 70 years old (odds ratio 1.09, 95% confidence interval
      0.53 to 2.24). In conclusion, female gender was associated with in-hospital
      mortality after acute myocardial infarction in patients >= 70 years old but not
      in patients < 70 years old.

PMID- 21726841
TI  - Comparison of effectiveness and safety of ranolazine versus amiodarone for
      preventing atrial fibrillation after coronary artery bypass grafting.
AB  - Atrial fibrillation (AF) is common after coronary artery bypass grafting (CABG)
      and increases the morbidity and cost. Amiodarone reduces AF after CABG.
      Ranolazine, an antianginal agent, also prolongs atrial refractoriness and
      inhibits after depolarizations and triggered activity; effects that could
      decrease AF after CABG. The present study compared amiodarone versus ranolazine
      for the prevention of AF after CABG. A retrospective cohort study of patients
      undergoing CABG at Aspirus Hospital from June 2008 to April 2010. The patients
      received either amiodarone (400 mg preoperatively followed by 200 mg twice daily
      for 10 to 14 days) or ranolazine (1,500 mg preoperatively followed by 1,000 mg
      twice daily for 10 to 14 days). The primary end point was any identified AF after
      CABG. A total of 393 consecutive patients undergoing CABG (mean age 65 +/- 10
      years, 72% men) received either amiodarone (n = 211 [53.7%]) or ranolazine (n =
      182 [46.3%]). AF occurred in 26.5% of the amiodarone-treated patients compared to
      17.5% of the ranolazine-treated patient (p = 0.035). The univariate predictors of
      AF included amiodarone use, age, chronic lung disease, and congestive heart
      failure. The multivariate predictors of AF included amiodarone use (odds ratio
      1.7, 95% confidence interval 1.01 to 2.91, p = 0.045 vs ranolazine), age (odds
      ratio 2.2 per 10 years, 95% confidence interval 1.63 to 2.95, p <0.001), and
      chronic lung disease (odds ratio 1.86, 95% confidence interval 1.00 to 3.43, p =
      0.049). No difference was found in the risk of adverse events between the 2
      therapies. In conclusion, ranolazine was independently associated with a
      significant reduction of AF compared to amiodarone after CABG, with no difference
      in the incidence of adverse events. Randomized studies should be conducted to
      confirm these results.

PMID- 21726842
TI  - Diagnostic classification of retinal nerve fiber layer measurement in myopic
      eyes: a comparison between time-domain and spectral-domain optical coherence
      tomography.
AB  - PURPOSE: To evaluate and compare the diagnostic classification of retinal nerve
      fiber layer (RNFL) measurement between time-domain and spectral-domain optical
      coherence tomography (OCT) in myopic eyes. DESIGN: Prospective, observational
      study. METHODS: A total of 97 eyes from 97 healthy myopic subjects were included.
      The RNFL in each eye was imaged sequentially with the Stratus OCT and the Cirrus
      HD-OCT (Carl Zeiss Meditec). With reference to the built-in normative database,
      the number of abnormal diagnostic classifications (borderline or outside normal
      limits) in each OCT device was analyzed and compared using the likelihood ratio
      chi-square test. Multiple logistic regression analysis was performed to evaluate
      factors associated with abnormal diagnostic classification. RESULTS: The Cirrus
      HD-OCT classified a significantly higher percentage of eyes as outside normal
      limits/borderline in at least 1 clock hour (Stratus, 14.4%/24.8%; Cirrus,
      21.6%/34.1%; all P < .01). RNFL measurement at 1 (23.6%) and 2 o'clock (23.5%) of
      all eyes was the most frequent location classified as abnormal by the Cirrus HD
      OCT and the Stratus OCT, respectively. Eyes with smaller optic disc and longer
      axial length were more likely to have abnormal diagnostic classification.
      CONCLUSIONS: In myopic eyes, Cirrus HD-OCT was more likely to have abnormal
      diagnostic classification than the Stratus OCT.

PMID- 21726843
TI  - 23-Gauge transconjunctival pars plana vitrectomy for removal of retained lens
      fragments.
AB  - PURPOSE: To examine the usefulness of 23-gauge pars plana vitrectomy (PPV) in
      removing retained lens fragments and to determine which cases require 20-gauge
      ultrasonic fragmentation. DESIGN: Retrospective comparative case series. METHODS:
      Twenty eyes in 20 consecutive patients who had 23-gauge PPV for retained lens
      fragments after complicated cataract surgery at Wills Eye Institute were
      retrospectively reviewed. Retained lens fragments were graded based on percentage
      of total nuclear size. Every surgical case started with 23-gauge PPV, but 1
      sclerotomy was enlarged to facilitate 20-gauge ultrasonic fragmentation if all
      lens material could not be adequately removed. RESULTS: Twelve patients (60%)
      were successfully managed with 23-gauge PPV alone while 8 patients (40%) required
      20-gauge ultrasonic fragmentation. The 23-gauge cases had a lower percentage of
      retained lens fragments (median 10%, range 0% to 75%) compared to the 20-gauge
      cases (median 90%, range 10% to 100%). CONCLUSION: 23-Gauge PPV is a feasible
      approach in the surgical management of select cases of retained lens fragments.

PMID- 21726844
TI  - Transient corneal thinning in eyes undergoing corneal cross-linking.
AB  - PURPOSE: To report the corneal thinning during and after corneal cross-linking
      (CXL). DESIGN: Prospective, nonrandomized, single-center observational study.
      METHODS: Thirty patients (30 eyes; 9 female, 21 male; age, 38 +/- 12 years) were
      consecutively scheduled for CXL between January 23 and July 6, 2009. Twenty-four
      eyes had progressive keratoconus, 2 had pellucid marginal degeneration, 3 eyes
      had progressive keratectasia after a LASIK operation, and 1 eye had pseudophakic
      bullous keratopathy. Riboflavin-ultraviolet A (UVA)-induced CXL included the
      instillation of 0.1% riboflavin drops for 30 minutes followed by riboflavin
      instillation combined with UVA irradiation for another 30 minutes. Corneal
      thickness was measured preoperatively, during CXL, and after 1 and 6 months using
      an ultrasound pachymeter. Changes in the endothelial cell count, corneal
      steepness, refraction, and visual performance are also given. RESULTS: On
      average, the corneas thinned 87 +/- 40 MUm (range, 37-206 MUm; 19% +/- 7%) during
      a 60-minute CXL treatment. In 1 patient, the cornea did not swell, even with
      hypotonic solution such that CXL would be safe. After 1 month, the corneal
      thickness was lower than the preoperative thickness, but after 6 months, the
      corneas had regained their original thicknesses. The endothelial cell count and
      corneal steepness were unchanged after CXL. The UCVA (uncorrected visual acuity)
      and BSCVA (best spectacle-corrected visual acuity) were improved 6 months after
      CXL. CONCLUSIONS: Corneal thickness decreases significantly during CXL, even to a
      level where the health of the endothelium and cornea is jeopardized. Visual
      performance is improved 6 months after CXL.

PMID- 21726845
TI  - Evidence of endothelial cell migration after descemet membrane endothelial
      keratoplasty.
AB  - PURPOSE: To investigate the hypothesis that adult corneal endothelial cells can
      migrate after Descemet membrane endothelial keratoplasty (DMEK). DESIGN:
      Prospective observational study. METHODS: Five patients with Fuchs endothelial
      dystrophy were examined 1 year after uneventful DMEK. These patients had been
      selected on the basis of slightly decentered grafts and/or large descemetorrhexis
      showing areas of denuded corneal stroma, which were covered by neither the
      patients' Descemet membrane (DM) nor the graft. These areas were investigated by
      in vivo confocal laser scanning microscopy using a specially designed Heidelberg
      Retina Tomograph II and Rostock cornea module equipped with custom-made software.
      Source data (frame rate 30 Hz, 384 * 384 pixels, 400 * 400 MUm) were used to
      create large-scale maps of the scanned area in automatic real-time composite
      mode. In each case an on-line mapping with maximum size up to 3.2 * 3.2 mm (3072
      * 3072 pixels) was performed. RESULTS: Corneal stroma overlying areas devoid of
      DM was transparent. In vivo confocal laser scanning microscopy of stroma devoid
      of DM revealed a monolayer of endothelial cells in all patients observed. The
      morphologic pattern of these cells was similar to that of endothelial cells on DM
      grafts but different from the morphology of the patients' own endothelium,
      suggesting migration of donor endothelial cells from DMEK grafts. CONCLUSIONS:
      The results strongly support the hypothesis that adult corneal endothelial cells
      are able to migrate in the human eye. Furthermore, we provide evidence to support
      the hypothesis that grafted endothelium migrates onto the host tissue,
      repopulating the corneal stroma with a regular endothelial phenotype.

PMID- 21726846
TI  - Soluble vascular endothelial growth factor receptor-2 and inflammatory factors in
      macular edema with branch retinal vein occlusion.
AB  - PURPOSE: To investigate relationships among vitreous fluid levels of soluble
      vascular endothelial growth factor receptor-2 (sVEGFR-2), vascular endothelial
      growth factor (VEGF), and soluble intercellular adhesion molecule 1 (sICAM-1) in
      patients with branch retinal vein occlusion (BRVO) and macular edema or patients
      with idiopathic macular hole. DESIGN: Retrospective case-control study. METHODS: 
      SETTING: Tokyo Women's Medical University and Eguchi Eye Hospital. PATIENT
      POPULATION: Forty-nine Japanese patients who underwent unilateral vitrectomy (27
      with BRVO and 22 with macular hole). OBSERVATION PROCEDURES: Vitreous fluid
      samples were obtained during vitreoretinal surgery to measure the levels of
      sVEGFR-2, VEGF, and sICAM-1. Retinal ischemia was evaluated from capillary
      nonperfusion on fluorescein angiography. Macular edema was examined by optical
      coherence tomography. MAIN OUTCOME MEASURES: Vitreous fluid levels of the 3
      molecules and severity of macular edema. RESULTS: BRVO patients had a
      significantly higher vitreous fluid level of sVEGFR-2 (median, 1670 pg/mL;
      interquartile range [IQL], 1205 to 2225 pg/mL) than macular hole patients
      (median, 1265 pg/mL; IQR, 731 to 1800 pg/mL; P = .017), as was the case for VEGF
      (median, 237 pg/mL; IQR, 42.2 to 1305 pg/mL; vs median, 15.6 pg/mL; IQR, 15.6 to
      15.6 pg/mL; P < .001) and sICAM-1 (median, 10.1 ng/mL; IQR, 6.3 to 22.5 ng/mL; vs
      median, 4.1 ng/mL; IQR, 3.3 to 6.0 ng/mL; P < .001). In BRVO patients, there was
      a significant positive correlation between vitreous fluid levels of sVEGFR-2 or
      VEGF and sICAM-1, but not between sVEGFR-2 and VEGF. Vitreous fluid levels of all
      3 molecules were correlated significantly the with severity of macular edema in
      BRVO patients. CONCLUSIONS: sVEGFR-2 may induce an increase of vascular
      permeability together with or via sICAM-1, or both with and via sICAM-1, in BRVO
      patients with macular edema.

PMID- 21726847
TI  - A randomized comparison of pupil-centered versus vertex-centered ablation in
      LASIK correction of hyperopia.
AB  - PURPOSE: To compare visual and optical outcomes of pupil-centered vs vertex
      centered ablation in patients undergoing laser-assisted in situ keratomileusis
      (LASIK) for hyperopia. DESIGN: Randomized, double-masked, prospective, single
      center trial. METHODS:  SETTING: Institutional practice. STUDY POPULATION: Sixty
      eyes of 30 patients with low and moderate hyperopia. Intervention procedure: Eyes
      underwent LASIK (Allegretto excimer laser). In 30 eyes, the ablation was centered
      on the pupil, while in the 30 other eyes the ablation was centered on the corneal
      reflex. MAIN OUTCOME MEASURES: Primary outcome measure was the safety index. Main
      secondary outcome measures were efficacy index, manifest refraction, uncorrected
      visual acuity, best spectacle-corrected visual acuity (BCVA), and ocular high
      order aberrations for a 6-mm pupil size. RESULTS: At 3 months postoperatively,
      the safety index was 0.99 +/- 0.04 in the pupil-centered group and 0.99 +/- 0.08
      in the vertex-centered group (P = .97). The efficacy index was also similar for
      both groups: 0.96 +/- 0.05 in pupil-centered eyes and 0.93 +/- 0.09 in vertex
      centered eyes (P = .31). Optical aberrations were similar for pupil-centered and
      vertex-centered eyes. Considering only eyes showing large pupil decentration, we
      found a tendency for better visual results in favor of pupil-centered eyes in
      terms of safety index and a slight but significant increase of coma in vertex
      centered eyes. CONCLUSION: LASIK is an effective procedure for treatment of
      hyperopia. Pupil-centered and vertex-centered treatments provide similar visual
      and optical outcomes. However, in eyes showing large temporal pupil decentration,
      pupil-centered ablation seemed to produce a lower amount of coma and, as a
      consequence, a reduced loss of BCVA compared with vertex-centered patients.

PMID- 21726848
TI  - Structural and functional correlation in sickle cell retinopathy using spectral
      domain optical coherence tomography and scanning laser ophthalmoscope
      microperimetry.
AB  - PURPOSE: To correlate macular structural changes by spectral-domain optical
      coherence tomography (SD-OCT) with functional changes by scanning laser
      ophthalmoscope (SLO) microperimetry testing in patients with sickle cell
      hemoglobinopathies. DESIGN: Prospective, investigational study. METHODS: Patients
      with electrophoretic confirmation of sickle cell hemoglobinopathies and normal
      subjects underwent SD-OCT and microperimetry testing with the OPKO Spectral
      OCT/SLO instrument. Based on SD-OCT findings, patients were grouped into those
      with focal macular thinning (Group A) and those without (Group B). Main outcome
      measure were mean retinal sensitivities measured by microperimetry and mean
      macular thicknesses in the 9 Early Treatment Diabetic Retinopathy Study (ETDRS)
      like subfields. RESULTS: Thirty-seven eyes of 19 patients with sickle cell
      hemoglobinopathies (SS, SC, and S-thalassemia) and 34 eyes of 34 age-similar
      normal controls were included. Mean age and mean logMAR best-corrected visual
      acuity between Groups A and B were not statistically different (39.7 years vs
      36.5 years, P = .64 and 0.015 vs 0.016, P = .93, respectively). Group A had
      significantly thinner retinas compared to Group B in the parafoveal superior (P =
      .019), parafoveal temporal (P < .004), parafoveal inferior (P = .003), perifoveal
      superior (P = .04), perifoveal temporal (P = .0005), and perifoveal inferior (P =
      .045) subfields. The overall mean microperimetry retinal sensitivities of Group A
      were significantly less than those of Group B (14.2 dB vs 16.5 dB, P = .00005).
      However, there was no statistical difference between Group B and controls (16.5
      dB vs 16.7 dB, P = .63). CONCLUSION: Sickle cell patients with focal macular
      thinning present on SD-OCT have significantly decreased retinal sensitivities
      compared to those without focal thinning or normal controls based on mean
      microperimetry sensitivities, despite similar age and visual acuity.
      Microperimetry is a sensitive measurement of macular function in patients with
      sickle cell hemoglobinopathies.

PMID- 21726849
TI  - Patterns of corneal endothelialization and corneal clearance after descemet
      membrane endothelial keratoplasty for fuchs endothelial dystrophy.
AB  - PURPOSE: To describe various endothelial migration healing patterns after
      Descemet membrane endothelial keratoplasty (DMEK), and to determine the
      contribution of the donor and host endothelium in the clearance of a transplanted
      cornea. DESIGN: Nonrandomized, prospective clinical study. METHODS: In a total of
      150 consecutive eyes that underwent DMEK (ie, transplantation of an isolated
      Descemet graft, for Fuchs endothelial dystrophy), re-endothelialization patterns
      were studied. Of these eyes, 36 showed a "stromal gap" between the
      "descemetorhexis edge" and the graft, or (partial) graft detachment.
      Endothelialization patterns of the host posterior stroma were documented at 1, 3,
      6, 9, 12, and 24 months after surgery with Pentacam imaging, specular microscopy,
      optical coherence tomography, confocal microscopy, and slit-lamp biomicroscopy.
      RESULTS: Complete corneal clearance was seen in 28 of 36 eyes (78%) with a
      stromal gap, or (partial) detachment, progressing from the periphery toward the
      center; and 27 of 34 eyes (79%) with normal visual potential reached a visual
      acuity of >=20/40 (>=0.5) or better. In 3 eyes that had the Descemet graft
      implanted upside-down, a "reversed corneal clearance pattern" was observed (ie,
      persistent edema where the graft was attached), while the area overlying the
      detachment cleared. One case that had a "descemetorhexis" performed without
      endothelial graft implantation showed persistent stromal edema. CONCLUSION: The
      presence of donor endothelium in the recipient anterior chamber may be required
      for endothelial migration and/or recovery of corneal clarity. Re
      endothelialization may be associated with massive endothelial migration and some
      form of cell signaling to draw donor endothelial cells toward the recipient
      posterior stroma ("homing").

PMID- 21726850
TI  - Prognostic indicators for no light perception after open-globe injury: eye injury
      vitrectomy study.
AB  - PURPOSE: To describe ocular characteristics, surgical interventions, and anatomic
      and visual outcomes of traumatized eyes with no light perception (NLP) following
      open-globe injury and to investigate prognostic predictors for NLP cases after
      open-globe injury. DESIGN: Interventional case series study. METHODS: Thirty
      three traumatized eyes with NLP were selected from the Eye Injury Vitrectomy
      Study database, a hospital-based multicenter prospective cohort study. Inclusion
      criteria were NLP cases following open-globe injury with outcomes of anatomic
      restoration, phthisis bulbi, or enucleation. Exclusion criteria were cases with
      missing records, undergoing vitrectomy after injury at nonparticipating
      hospitals, direct optic head injury, endophthalmitis, and hypotonous or silicone
      oil-sustained eyes. All cases underwent vitreoretinal surgery or enucleation
      after exploratory surgery and were followed up for at least 6 months. Two
      outcomes were assessed: favorable outcome (anatomically restored eye globes with
      light perception [LP] or better vision) and unfavorable outcome (NLP, phthisis
      bulbi, or enucleation). RESULTS: The following 7 risk factors were significant
      between the 2 groups: rupture (P = .021); open globe III (P = .046); scleral
      wound >=10 mm (P = .001); ciliary body damage (P < .001); severe intraocular
      hemorrhage (P = .005); closed funnel retinal detachment or retinal prolapse (P =
      .005); and choroidal damage (P = .001). CONCLUSIONS: These 7 risk factors are
      possible predictors of poor prognosis. Traumatized eyes with NLP can be
      anatomically restored with LP or better vision if vitreoretinal surgery is
      attempted, and a favorable anatomic and visual outcome is increased by having a
      decreased number of these risk factors.

PMID- 21726851
TI  - Split cornea transplantation for 2 recipients - review of the first 100
      consecutive patients.
AB  - PURPOSE: To evaluate the feasibility of split cornea transplantation for 2
      recipients by combining deep anterior lamellar keratoplasty (DALK) and Descemet
      membrane endothelial keratoplasty (DMEK). DESIGN: Interventional case series.
      METHODS: Fifty consecutive eyes with anterior stromal disease suitable for DALK
      and 50 eyes with endothelial disease suitable for DMEK were scheduled for split
      cornea transplantation combining both procedures within 72 hours. Main outcome
      measures included success of using a single donor cornea for 2 recipients, best
      spectacle-corrected visual acuity (BSCVA), and complication rates within 6
      months' follow-up. RESULTS: A single donor cornea could be used for 2 recipients
      in 47 cases (94%). In 3 eyes (6%), the DALK procedure had to be converted to
      penetrating keratoplasty (PK) requiring a full-thickness corneal graft. Thereby,
      47 donor corneas (47%) could be saved. Six months after surgery, mean BSCVA was
      20/36 in the 47 eyes that underwent successful DALK, 20/50 in the 3 eyes that
      underwent conversion from DALK to PK, and 20/29 in the 50 eyes that underwent
      DMEK. Postoperative complications after DALK included Descemet folds in 5 eyes
      (11%) and epitheliopathy in 3 eyes (6%). After DMEK, partial graft detachment
      occurred in 26 eyes (52%) and was managed successfully with intracameral air
      reinjection. All corneas remained clear up to 6 months after surgery. No
      intraocular infections occurred. CONCLUSION: Split use of donor corneal tissue
      for combined DALK and DMEK procedures in 2 recipients within 3 subsequent days is
      a feasible approach to reduce donor shortage in corneal transplantation in the
      future.

PMID- 21726852
TI  - A visual ergonomics intervention in mail sorting facilities: effects on eyes,
      muscles and productivity.
AB  - Visual requirements are high when sorting mail. The purpose of this visual
      ergonomics intervention study was to evaluate the visual environment in mail
      sorting facilities and to explore opportunities for improving the work situation
      by reducing visual strain, improving the visual work environment and reducing
      mail sorting time. Twenty-seven postmen/women participated in a pre-intervention
      study, which included questionnaires on their experiences of light, visual
      ergonomics, health, and musculoskeletal symptoms. Measurements of lighting
      conditions and productivity were also performed along with eye examinations of
      the postmen/women. The results from the pre-intervention study showed that the
      postmen/women who suffered from eyestrain had a higher prevalence of
      musculoskeletal disorders (MSD) and sorted slower, than those without eyestrain.
      Illuminance and illuminance uniformity improved as a result of the intervention.
      The two post-intervention follow-ups showed a higher prevalence of MSD among the
      postmen/women with eyestrain than among those without. The previous differences
      in sorting time for employees with and without eyestrain disappeared. After the
      intervention, the postmen/women felt better in general, experienced less work
      induced stress, and considered that the total general lighting had improved. The
      most pronounced decreases in eyestrain, MSD, and mail sorting time were seen
      among the younger participants of the group.

PMID- 21726853
TI  - Effects of four types of non-obtrusive feedback on computer behaviour, task
      performance and comfort.
AB  - This study investigated the effects of non-obtrusive feedback on continuous
      lifted hand/finger behaviour, task performance and comfort. In an experiment with
      24 participants the effects of two visual and two tactile feedback signals were
      compared to a no-feedback condition in a computer task. Results from the
      objective measures showed that all types of feedback were equally effective to
      reduce lifted hand/finger behaviour (effectiveness) compared to absence of
      feedback, while task performance was not affected (efficiency). In contrast to
      objective measures, subjective user experience was significantly different for
      the four types of feedback signals. Continuous tactile feedback appeared to be
      the best signal; not only the effectiveness and efficiency were rated reasonable,
      it also scored best on perceived match between signal and required action. This
      study shows the importance of including user experiences when investigating
      usability of feedback signals. Non-obtrusive feedback embedded in products and
      environments may successfully be used to support office workers to adopt healthy,
      productive and comfortable working behaviour.

PMID- 21726854
TI  - Characterization of posture and comfort in laptop users in non-desk settings.
AB  - Laptop computers may be used in a variety of postures not coupled to the office
      workstation. Using passive motion analysis, this study examined mean joint angles
      during a short typing/editing task in college students (n=20), in up to seven
      positions. Comfort was assessed after task execution through a body map. For
      three required postures, joint angles in a prone posture were different than
      those while seated at a couch with feet either on floor or on ottoman.
      Specifically, the prone posture was characterized by comparatively non-neutral
      shoulders, elbows and wrists, and pronounced neck extension. Significantly
      greater intensity and more regions of discomfort were marked for the prone
      posture than for the seated postures. It is recommended that the prone posture
      only be assumed briefly during laptop use. Exposure to laptops outside of the
      office setting should be assessed in future epidemiologic studies of
      musculoskeletal complaints and computer use.

PMID- 21726855
TI  - Mirror gazing in body dysmorphic disorder and healthy controls: effects of
      duration of gazing.
AB  - Cognitive-behavioural models of body dysmorphic disorder (BDD) suggest that
      mirrors can act as a trigger for individuals with BDD, resulting in a specific
      mode of cognitive processing, characterised by an increase in self-focussed
      attention and associated distress. The aim of the current study was to
      investigate these factors experimentally by exposing participants with BDD (n=25)
      and without BDD (n=25) to a mirror in a controlled setting. An additional aim was
      to ascertain the role of duration of mirror gazing in the maintenance of distress
      and self-consciousness by manipulating the length of gazing (short check vs. long
      gazing). Findings demonstrated that contrary to what was predicted, not only
      participants with BDD, but also those without BDD experienced an increase in
      distress and self-focused attention upon exposure to the mirror. In addition,
      people without BDD, unlike those with BDD, experienced more distress when looking
      in the mirror for a long period of time as opposed to a short period of time.
      This lends some support to the idea that, for people with BDD, gazing in a
      mirror, regardless of duration, might act as an immediate trigger for an abnormal
      mode of processing and associated distress, and that this association has
      developed from past excessive mirror gazing. Further theoretical implications of
      these findings, as well as subsidiary research questions relating to additional
      cognitive factors are discussed.

PMID- 21726856
TI  - Continuous visual cues trigger automatic spatial target updating in dynamic
      scenes.
AB  - Dynamic tasks often require fast adaptations to new viewpoints. It has been shown
      that automatic spatial updating is triggered by proprioceptive motion cues. Here,
      we demonstrate that purely visual cues are sufficient to trigger automatic
      updating. In five experiments, we examined spatial updating in a dynamic
      attention task in which participants had to track three objects across scene
      rotations that occurred while the objects were temporarily invisible. The objects
      moved on a floor plane acting as a reference frame and unpredictably either were
      relocated when reference frame rotations occurred or remained in place. Although
      participants were aware of this dissociation they were unable to ignore
      continuous visual cues about scene rotations (Experiments 1a and 1b). This even
      held when common rotations of floor plane and objects were less likely than a
      dissociated rotation (Experiments 2a and 2b). However, identifying only the
      spatial reference direction was not sufficient to trigger updating (Experiment
      3). Thus we conclude that automatic spatial target updating occurs with pure
      visual information.

PMID- 21726857
TI  - The influence of Bone Morphogenic Protein-2 on the consolidation phase in a
      distraction osteogenesis model.
AB  - We asked whether locally applied recombinant-Bone Morphogenic Protein-2 (rh-BMP
      2) with an absorbable Type I collagen sponge (ACS) carrier could enhance the
      consolidation phase in a callotasis model. We performed unilateral transverse
      osteotomy of the tibia in 21 immature male rabbits. After a latency period of 7
      days, a 3-weeks distraction was begun at a rate of 0.5mm/12h. At the end of the
      distraction period (Day 28) animals were randomly divided into three groups and
      underwent a second surgical procedure: 6 rabbits in Group I (Control group; the
      callus was exposed and nothing was added), 6 rabbits in Group II (ACS group;
      receiving the absorbable collagen sponge soaked with saline) and 9 rabbits in
      Group III (rh-BMP-2/ACS group; receiving the ACS soaked with 100MUg/kg of rh-BMP
      2, Inductos((r)), Medtronic). Starting at Day 28 we assessed quantitative and
      qualitative radiographic parameters as well as densitometric parameters every two
      weeks (Days 28, 42, 56, 70 and 84). Animals were sacrificed after 8 weeks of
      consolidation (Day 84). Qualitative radiographic evaluation revealed hypertrophic
      calluses in the Group III animals. The rh-BMP-2/ACS also influenced the
      development of the cortex of the calluses as shown by the modified radiographic
      patterns in Group III when compared to Groups I and II. Densitometric analysis
      revealed the bone mineral content (BMC) was significantly higher in the rh-BMP
      2/ACS treated animals (Group III).

PMID- 21726858
TI  - Minimal injury of the descending aorta secondary to blunt trauma.

PMID- 21726859
TI  - Femoral-shaft fractures and nonunions treated with intramedullary nails: the role
      of dynamisation.
AB  - Dynamisation of a previously interlocked intramedullary nail is believed to
      stimulate an osteogenic response due to increased load across the fracture site.
      The purpose of this study was to retrospectively investigate fracture patterns
      that could tolerate dynamisation without the risk of major complications. Thirty
      patients (24 males) with an average age of 33 years (17-90) were studied. As many
      as 21 suffered from a fresh femoral fracture, whereas the remaining nine patients
      suffered from femoral nonunions. Four patterns of osseous lesion were recognised
      in terms of mechanical stability under a dynamic nail and biological activity at
      the fracture/nonunion site: stable/hypertrophic, stable/atrophic,
      unstable/hypertrophic and unstable/atrophic osseous lesions. Complete union
      (within 6 months) occurred in 21 patients. Six fractures united within the 7th
      11th post-dynamisation month and, in the remaining three cases, a nonunion
      developed. Significant femur shortening (>20 mm) was noticed in four patients and
      rotational malalignment in one patient. Logistic regression analysis revealed
      high odds ratio (OR=70, 95% confidence interval (CI) 2.5-1998) for the
      unstable/atrophic pattern of osseous lesion to develop major complications. In
      the unstable/atrophic pattern of osseous lesion, dynamisation should never be
      done, as it could lead to significant complications.

PMID- 21726860
TI  - Risk factors for cervical spine injury.
AB  - INTRODUCTION: The early recognition of cervical spine injury remains a top
      priority of acute trauma care. Missed diagnoses can lead to exacerbation of an
      existing injury and potentially devastating consequences. We sought to identify
      predictors of cervical spine injury. METHODS: Trauma registry records for blunt
      trauma patients cared for at a Level I Trauma Centre from 1997 to 2002 were
      examined. Cervical spine injury included all cervical dislocations, fractures,
      fractures with spinal cord injury, and isolated spinal cord injuries. Univariate
      and adjusted odds ratios (ORs) were calculated to identify potential risk
      factors. Variables and two-way interaction terms were subjected to multivariate
      analysis using backward conditional stepwise logistic regression. RESULTS: Data
      from 18,644 patients, with 55,609 injuries, were examined. A total of 1255
      individuals (6.7%) had cervical spine injuries. Motor Vehicle Collision (MVC)
      (odds ratio (OR) of 1.61 (1.26, 2.06)), fall (OR of 2.14 (1.63, 2.79)), age <40
      (OR of 1.75 (1.38-2.17)), pelvic fracture (OR of 9.18 (6.96, 12.11)), Injury
      Severity Score (ISS) >15 (OR of 7.55 (6.16-9.25)), were all significant
      individual predictors of cervical spine injury. Neither facial fracture nor head
      injury alone were associated with an increased risk of cervical spine injury.
      Significant interactions between pelvic fracture and fall and pelvic fracture and
      head injury were associated with a markedly increased risk of cervical spine (OR
      19.6 (13.1, 28.8)) and (OR 27.2 (10.0-51.3)). CONCLUSIONS: MVC and falls were
      independently associated with cervical spine injury. Pelvic fracture and fall and
      pelvic fracture and head injury, had a greater than multiplicative interaction
      and high risk for cervical spine injury, warranting increased vigilance in the
      evaluation of patients with this combination of injuries.

PMID- 21726861
TI  - PPARgamma in coronary atherosclerosis: in vivo expression pattern and
      correlations with hyperlipidemic status and statin treatment.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is
      involved in regulation of macrophage inflammation and in atherosclerosis. Herein
      we investigate the influence of statin treatment on PPARgamma expression in
      coronary artery disease. METHOD: PPARgamma expression was investigated in
      coronary atherosclerotic atherectomies (N=48) and arteries (N=12) from patients
      with stable or unstable coronary syndromes or undergoing cardiac transplantation
      for end-stage ischemic cardiomyopathy, respectively, by immunohistochemistry.
      Plaque components and tissue factor immunoreactivity were also investigated.
      Atherectomies were obtained from de novo culprit lesions of hypercholesterolemic
      (16 statin-treated and 16 untreated) and normolipidemic (N=16) patients.
      Furthermore, PPARgamma expression was evaluated in patients peripheral blood
      monocytes and in monocytic U937 cells after atorvastatin incubation, by Western
      blot analysis. RESULT: PPARgamma expression was higher in coronary plaques and
      peripheral blood monocytes of statin-treated patients, and it significantly
      increased in monocytes after 24h atorvastatin incubation (p<0.05). Intra-plaque
      macrophage content, atheroma, neoangiogenesis and hemorrhage, and circulating CRP
      levels were lower in statin-treated than untreated hypercholesterolemic patients
      and comparable with normolipidemic subjects. PPARgamma immunoreactivity was
      localized to neointima and media, its distribution pattern being different from
      that of tissue factor. CONCLUSION: PPARgamma expression was enhanced in statin
      treated patients with different distribution and behavior as compared to
      atheroma, macrophage content, tissue factor immunoreactivity and serum CRP. In
      vitro studies showed increased PPARgamma expression in monocytes after
      atorvastatin incubation. These findings provide further evidence as to the
      protective role of statins in coronary artery disease and their influence on
      PPARgamma expression in coronary plaques and on the inflammatory status of
      patients.

PMID- 21726862
TI  - Associations of cardiovascular risk factors, carotid intima-media thickness and
      left ventricular mass with inter-adventitial diameters of the common carotid
      artery: the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Common carotid artery inter-adventitial diameter (IAD) and intima
      media thickness (IMT) are measurable by ultrasound. IAD may be associated with
      left ventricular mass (LV mass) while IMT is a marker of subclinical
      atherosclerosis. It is not clear if IAD is associated with LV mass after
      accounting for IMT and traditional cardiovascular risk factors. METHODS: IAD and
      IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis
      (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814
      MESA participants were studied. LV mass was measured by magnetic resonance
      imaging. Multivariable linear regression was used with IAD as the outcome and
      adjustment for risk factors, as well as IMT and LV mass. RESULTS: Traditional
      cardiovascular risk factors, height, weight and ethnicity were significantly
      associated with IAD. After adjustment for risk factors, a 1mm difference in IMT
      was associated with a 1.802mm (95% CI: 1.553, 2.051) higher mean IAD. A 1g
      difference in LV mass was associated with a 0.006mm (95% CI: 0.005, 0.007) higher
      mean IAD. After adjusting for cardiovascular risk factors and IMT, a 1g
      difference in LV mass was associated with a 0.006mm (95% CI: 0.005, 0.008) higher
      mean IAD for women and 0.004mm (95% CI: 0.003, 0.005) higher IAD for men.
      CONCLUSIONS: Inter-adventitial diameters are associated with left ventricular
      mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as
      a surrogate for left ventricular mass and have predictive value for
      cardiovascular outcomes.

PMID- 21726863
TI  - The NFKB1 ATTG ins/del polymorphism and risk of coronary heart disease in three
      independent populations.
AB  - AIM: Inflammation is a risk factor for coronary heart disease (CHD). A common
      deletion-allele in the promoter region of NFKB1 results in lower protein levels
      of the NF-kappaB p50 subunit. Recent evidence suggests that the NF-kappaB p50
      dimer has anti-inflammatory effects. We aimed to investigate the association of
      the functional ATTG NFKB1 insertion/deletion variant with risk of CHD in three
      independent prospective studies of generally healthy men and women. METHODS AND
      RESULTS: The NFKB1 ins/del polymorphism was genotyped in studies of CHD nested
      within the Diet, Cancer and Health (DCH) study, the Health Professionals Follow
      up (HPFS) and the Nurses' Health (NHS) studies, totaling 1008, 428 and 439 cases,
      respectively. The minor allele frequency in the combined sample was 0.38 among
      controls. In a pooled analysis, the relative risk (RR) among heterozygous men and
      women was 1.22 (95% CI: 1.07-1.40), compared to the most common ins/ins genotype.
      The RR among homozygotes was 1.20 (95% CI: 0.94-1.53). There was no evidence of
      an allele-dosage effect, and in a dominant model the RR among del-allele carriers
      was 1.22 (95% CI: 1.07-1.39). The risk was similar in women and men (RR was 1.20
      in women and 1.23 in men, respectively). The NFKB1 variant was not associated
      with plasma lipid levels, but del-carriers had lower levels of C-reactive
      protein. CONCLUSIONS: The NFKB1 promoter variant, previously shown to cause
      partial depletion of NF-kappaB p50, was associated with a higher risk of CHD in
      three independent prospective studies of generally healthy Caucasians.

PMID- 21726864
TI  - Elevated plasma asymmetric dimethylarginine level in acute myocardial infarction
      patients as a predictor of poor prognosis and angiographic impaired reperfusion.
AB  - OBJECTIVES: We aimed to investigate the effects of admission asymmetric
      dimethylarginine (ADMA) levels on myocardial perfusion and prognosis in ST
      segment elevation myocardial infarction (STEMI) patients undergoing primary
      percutaneous coronary intervention (PCI). BACKGROUND: ADMA, an endogenous
      inhibitor of endothelial nitric oxide synthase, was found to be elevated in
      plasma of patients with cardiovascular risk factors. METHODS: 168 consecutive
      patients undergoing primary PCI for STEMI <12 h after symptom onset and 75
      healthy age and sex matched volunteer controls were enrolled in the study.
      Patients with STEMI were grouped into tertiles according to their admission
      plasma ADMA levels. Major adverse cardiac events during hospitalization or at one
      year clinical follow-up were evaluated. Also angiographic impaired reperfusion
      was assessed by 3 different methods after PCI: angiographic thrombolysis in
      myocardial infarction (TIMI) flow, TIMI frame count and TIMI myocardial perfusion
      grade (TMPG). RESULTS: Plasma level of L-arginine were lower in patients with
      STEMI than in the control group subjects, whereas plasma ADMA levels were
      increased in the STEMI patient group. The rate of impaired angiographic
      reperfusion increased across the tertile groups. Also one-year mortality rates
      showed a significant increase across the tertile groups (4% vs. 10% vs. 20%,
      p<0.01). Using multiple Cox regression analysis, only TIMI risk score, left
      ventricle ejection fraction (LVEF), abnormal TMPG, and increased ADMA values on
      admission emerged as independent predictors of one-year mortality. The ROC
      analysis indicated an optimal cut-point of >=1.37 MUmol/L, which detects one-year
      mortality with a negative predictive value of 96%. CONCLUSIONS: In STEMI patients
      undergoing primary PCI, high admission ADMA levels were found to be associated
      with impaired myocardial perfusion and increased one-year mortality. Therefore
      admission ADMA level detection may be helpful in identifying the patients at a
      greater risk of impaired myocardial perfusion and poor prognosis.

PMID- 21726865
TI  - Effects of reduced plantar cutaneous afferent feedback on locomotor adjustments
      in dynamic stability during perturbed walking.
AB  - This study examined the effects of reduced plantar cutaneous afferent feedback on
      predictive and feedback adaptive locomotor adjustments in dynamic stability
      during perturbed walking. Twenty-two matched participants divided between an
      experimental-group and a control-group performed a gait protocol, which included
      surface alterations to one covered exchangeable gangway-element (hard/soft). In
      the experimental-group, cutaneous sensation in both foot soles was reduced to the
      level of sensory peripheral neuropathy by means of intradermal injections of an
      anaesthetic solution, without affecting foot proprioception or muscles. The gait
      protocol consisted of baseline trials on a uniformly hard surface and an
      adaptation phase consisting of nineteen trials incorporating a soft gangway
      element, interspersed with three trials using the hard surface-element (2nd, 8th
      and 19th). Dynamic stability was assessed by quantifying the margin of stability
      (MS), which was calculated as the difference between the base of support (BS) and
      the extrapolated centre of mass (CM). The horizontal velocity of the CM and its
      vertical projection in the anterior-posterior direction and the eigenfrequency of
      an inverted pendulum determine the extrapolated-CM. Both groups increased the BS
      at the recovery step in response to the first unexpected perturbation. These
      feedback corrections were used more extensively in the experimental-group, which
      led to a higher MS compared to the control-group, i.e. a more stable body
      position. In the adaptation phase the MS returned to baseline similarly in both
      groups. In the trial on the hard surface directly after the first perturbation,
      both groups increased the MS at touchdown of the disturbed leg compared to
      baseline trials, indicating rapid predictive adjustments irrespective of plantar
      cutaneous input. Our findings demonstrate that the locomotor adaptational
      potential does not decrease due to the loss of plantar sensation.

PMID- 21726866
TI  - Capillary zone electrophoresis for the analysis of glycoforms of
      cellobiohydrolase.
AB  - Cellobiohydrolase (CBH) is an important enzyme for the conversion of
      lignocellulosic biomass to ethanol. This work separated the glycoforms of CBH
      possessing different numbers of neutral mannoses using capillary zone
      electrophoresis (CZE) in a 50 mM, pH 7.5 phosphate buffer. The method analysed
      CBH in an intact form using a polyacrylamide coated fused silica capillary
      without requiring additives or labelling of the enzyme. The migration time of the
      major peak was found to be 21.6+/-0.1 min (n=3) and the approach is suitable for
      testing of batch-to-batch consistency of CBH. Ease-of-use, automation and speed
      are the other benefits due to which the use of CZE for analysing glycoforms of
      CBH was concluded to be ideal.

PMID- 21726867
TI  - A study of mass transfer kinetics of alanyl-alanine on a chiral crown ether
      stationary phase.
AB  - The mass transfer kinetics of alanyl-alanine enantiomers in a column packed with
      a chiral stationary phase (CSP) ChiroSil RCA(+) was studied by means of the
      moment method. Methanol-water solutions acidified with sulphuric acid were used
      as the mobile phase. It was shown that the spreading of peaks in the column was
      strongly affected by abnormal eddy diffusion. This effect was well described
      within the framework of the Giddings coupling theory. The comprehensive four-term
      Giddings equation for eddy diffusion was applied, considering simultaneous
      contribution of the trans-column, trans-channel, short-range inter-channel, and
      long-range inter-channel dispersion factors. Through these calculations, a
      predominant importance of the trans-column flow velocity bias was revealed.
      Besides eddy diffusion, the adsorption kinetic resistance to mass transfer plays
      a noticeable role in band broadening, all the other contributions (from
      longitudinal molecular diffusion, external and intraparticle mass transfer) being
      of minor significance. A relative importance of the mass transfer kinetics
      increases correlatively with a growth of the retention factor. Both the retention
      and kinetics of the adsorption of alanyl-alanine on the CSP in study are
      enantioselective. The influence of the column pressure on retention as well as
      corrections required because of this influence are also discussed.

PMID- 21726868
TI  - The impact of extra-column band broadening on the chromatographic efficiency of 5
      cm long narrow-bore very efficient columns.
AB  - Small columns packed with core-shell and sub-2 MUm totally porous particles and
      monolith columns are very popular to conduct fast and efficient chromatographic
      separations. In order to carry out fast separations, short (2-5 cm) and narrow
      bore (2-2.1 mm) columns are used to decrease the analyte retention volume. Beside
      the column efficiency, another significant issue is the extra-column band
      spreading. The extra-column dispersion of a given LC system can dramatically
      decrease the performance of a small very efficient column. The aim of this study
      was to compare the extra-column peak variance contribution of several
      commercially available LC systems. The efficiency loss of three different type 5
      cm long narrow bore, very efficient columns (monolith, sub-2 MUm fully porous and
      sub-2 MUm core-shell packing) as a function of extra-column peak variance, and as
      a function of flow rate and also kinetic plots (analysis time versus apparent
      column efficiency) are presented.

PMID- 21726869
TI  - Multiple headspace solid-phase microextraction of ethyl carbamate from different
      alcoholic beverages employing drying agent based matrix modification.
AB  - Multiple headspace solid-phase microextraction (MHS-SPME) combined with gas
      chromatography-nitrogen phosphorus detector is proposed to determine the toxic
      contaminant ethyl carbamate (EC) in various alcoholic beverages after matrix
      modification. The remarkable feature of this method is that matrix effect, which
      commonly appears in SPME-based analysis, is avoided by determining the total
      amount of the analyte in the sample. To increase the sensitivity of the method, a
      novel polyethylene glycol/hydroxy-terminated silicone oil fiber was developed by
      sol-gel technique and applied for the analysis. Owing to the high polarity and
      hydrophilia of EC, an important problem still remains because the adsorption by
      sample matrix causes low transport of EC to the headspace and thus invalidates
      MHS-SPME for quantification. Mixing with anhydrous sodium sulphate, the
      sensitivity of the method can be improved. A Taguchi's L(16) (4(5)) orthogonal
      array design was employed to evaluate potentially significant factors and screen
      the optimum conditions for MHS-SPME of EC. Under the optimized conditions, limit
      of detection of 0.034 mg L(-1) was obtained. Relative standard deviation of
      replicate samples (n=6) was 2.19%. The proposed method was linear in the range of
      0.04-100 mg L(-1), and the coefficient of determination was 0.9997. The method
      was used to determine EC in various alcoholic beverages. The concentrations
      obtained were compared with those obtained by standard addition method and no
      statistically significant differences were observed.

PMID- 21726870
TI  - Computational modeling of capillary electrophoretic behavior of primary amines
      using dual system of 18-crown-6 and beta-cyclodextrin.
AB  - Using capillary electrophoresis (CE) three chiral primary amine compounds 1
      aminoindan (AI), 1-(1-naphthyl)ethylamine (NEA) and 1,2,3,4-tetrahydro-1
      naphthylamine (THAN), exhibited only partial or no separation when beta
      cyclodextrin (betaCD) was used as chiral selector. The use of 18-crown-6 (18C6)
      as a second additive with betaCD resulted in an enhanced separation. A molecular
      modeling study, using molecular mechanics and the semiempirical PM6 calculations,
      was used to help explaining the mechanism of the enantiodifferentiation and to
      predict the separation process. Optimization of the structures of the complexes
      by the PM6 method indicate that the poor separation obtained in the presence of
      the betaCD chiral selector alone is due to the small binding energy differences
      (DeltaDeltaE) of 4.7, 1.1 and 1.2 kcal mol(-1) for AI, NEA and THAN,
      respectively. In the presence of 18C6 it was suggested that a sandwich compound
      between 18C6, amine and betaCD is formed. Theoretical calculations show that a
      significant increase in the binding energy is obtained for the sandwich compounds
      indicating strong hydrophobic and van der Waals interactions that show enhanced
      enantiodifferentiation.

PMID- 21726871
TI  - Static and dynamic binding capacities of human immunoglobulin G on
      polymethacrylate based mixed-modal, thiophilic and hydrophobic cation exchangers.
AB  - The aim of this study was to investigate functional increments of ion exchange
      type ligands, which may improve the performance of mixed-modal ligands for
      antibody capture out of feed solutions with pH above 6.0 and containing sodium
      chloride concentrations of 150 mM and higher. For this purpose several functional
      groups such as sulfonyl, sulfanyl, amide, methoxy, short alkyl and aromatic
      moieties were tested in combination with a strong sulfonic acid and/or a weak
      carboxylic acid group. Therefore a series of ligands were synthesized and
      subsequently coupled onto epoxide activated Fractogel((r)) EMD. In the first
      instance, all materials were tested by static binding capacity measurements (SBC)
      under test conditions, comprising a wide variety of different sodium chloride
      concentrations and differing pH values ranging from 4.5 to 7.5. From these
      preliminary experiment it was found that especially the aromatic groups improved
      the binding of human immunoglobulin G (h-IgG) under isotonic conditions, while
      other increments, e.g. thiophilic or amide groups, were not able to increase the
      capacity significantly. Taking the SBC results into account, the most promising
      materials were investigated under dynamic binding conditions (DBC) with a reduced
      selection of test conditions (pH 5.5, 6.5 and 7.4 at 75 and 150mM NaCl). N
      benzoyl-homocysteine (material J) and 3,5-dimethoxybenzoyl-homocysteine (material
      K) showed 100% DBCs of 37 mg/mL and 32 mg/mL in the presence of 75 mM NaCl and pH
      6.5. Material L carrying mercaptobenzoic acid as a ligand and tested with the
      same solution provided a 100% DBC of 68 mg/mL. The influence of Pluronic F68 in a
      mock feed solution as well as in cell culture supernatant was investigated with
      the best performing bio-affinity type adsorbent, material L. For the real sample
      feed subsequent SDS-PAGE was conducted for the collected fractions.

PMID- 21726872
TI  - Downstream processing of Vero cell-derived human influenza A virus (H1N1) grown
      in serum-free medium.
AB  - A downstream processing was examined for Vero cell-derived human influenza virus
      (H1N1) grown in serum free medium. Vero cell banks were established in serum free
      medium and characterized according to regulatory requirements. Serum free Vero
      cells were grown on Cytodex 3 microcarriers in 5L bioreactor and infected with
      influenza A virus (A/New Caledonia/99/55). The harvests were processed with the
      sequence of inactivation, clarification, anion exchange chromatography (DEAE FF),
      Cellufine Sulfate Chromatography (CSC) and size exclusion chromatography
      (Sepharose 6FF). Host cell DNA (hcDNA) was mainly removed with DEAE FF column and
      CSC by 40 and 223 fold, respectively. Most of Vero cell proteins were eliminated
      in CSC and Sepharose 6FF unit operation by about 13 fold. The overall scheme
      resulted in high recovery of hemagglutinin (HA) activity and the substantial
      removal of total protein, host protein and DNA. The total protein content and DNA
      content per 15 MUg HA protein in final product was 89 MUg and 33 pg,
      respectively, which complied with regulatory requirements for single strain
      influenza vaccines. SDS-PAGE analysis and Western blotting confirmed the purity
      of the final product. In conclusion, the suggested downstream process is suitable
      for the purification of microcarrier-based cell-derived influenza vaccine.

PMID- 21726873
TI  - Morphological analysis of physically reconstructed capillary hybrid silica
      monoliths and correlation with separation efficiency.
AB  - We report an experimental study on the structural (especially radial)
      heterogeneity of eleven 100 MUm i.d. capillary tetramethoxysilane
      methyltrimethoxysilane hybrid silica monoliths with different pore and skeleton
      sizes, which were imaged by an optimized confocal laser scanning microscopy
      method. This method allows the optical sectioning of the monoliths, which is a
      prerequisite for quantitative morphological image analysis. Both radial porosity
      profiles and chord length distributions were calculated in the macropore domain
      for each column from at least 100 complete cross-sectional views along the column
      axis. The statistical approach visualized radial heterogeneities on different
      length scales in the monolithic structures. Chord length distributions followed a
      simplified k-gamma function, and a structural parameter obtained from this
      function is introduced to provide a scalar measure of column heterogeneity. It
      enables the comparison of monoliths with different pore sizes and helps to
      establish correlations between the microscopic properties of a column, eddy
      dispersion, and its separation efficiency.

PMID- 21726874
TI  - Determination of suspected fragrance allergens in cosmetics by matrix solid-phase
      dispersion gas chromatography-mass spectrometry analysis.
AB  - An effective low cost sample preparation methodology for the determination of
      regulated fragrance allergens in leave-on and rinse-off cosmetics has been
      developed applying, for the first time, matrix solid-phase dispersion (MSPD) to
      this kind of analytes and samples. The selection of the most suitable extraction
      conditions was made using statistical tools such as ANOVA, as well as a factorial
      multifactor experimental design. These studies were carried out using real
      cosmetic samples. In the final conditions, 0.5 of sample, previously mixed with
      1g of anhydrous Na(2)SO(4), were blended with 2g of dispersive sorbent
      (Florisil), and the MSPD column was eluted with 5 mL of hexane/acetone (1:1). The
      extract was then analyzed by GC-MS without any further clean-up or concentration
      step. Accuracy, precision, linearity and detection limits (LODs) were evaluated
      to assess the performance of the proposed method. Quantitative recoveries (>75%)
      were obtained and RSD values were lower than 10% in all cases. The quantification
      limits were well below those set by the international cosmetic regulations,
      making this multi-component analytical method suitable for routine control. In
      addition, the MSPD method can be implemented in any laboratory at low cost since
      it does not require special equipment. Finally, a wide variety of cosmetic
      products were analyzed. All the samples contained several of the target cosmetic
      ingredients, with and average number of seven. The total fragrance allergen
      content was in general quite high, even in baby care products, with values close
      to or up to 1%, for several samples, although the actual European Cosmetic
      Regulation was fulfilled.

PMID- 21726875
TI  - Oxidized multi-walled carbon nanotubes for the dispersive solid-phase extraction
      of quinolone antibiotics from water samples using capillary electrophoresis and
      large volume sample stacking with polarity switching.
AB  - In this work, a new method for the determination of eleven quinolone antibiotics
      (moxifloxacin, lomefloxacin, danofloxacin, ciprofloxacin, levofloxacin,
      marbofloxacin, enrofloxacin, difloxacin, pefloxacin, oxolinic acid and
      flumequine) in different water samples using dispersive solid-phase extraction
      (dSPE) and capillary zone electrophoresis with diode-array detection was
      developed. Oxidized multi-walled carbon nanotubes (o-MWCNTs) were used for the
      first time as stationary phases for the off-line preconcentration by dSPE of the
      antibiotics. A 65 mM phosphate buffer at pH 8.5 was found adequate for analyte
      separation while large volume sample stacking with polarity switching of the
      analytes dissolved in water containing 10% (v/v) of acetonitrile was carried out
      in order to improve the sensitivity. dSPE parameters, such as sample volume and
      pH, o-MWCNT amount, volume and type of eluent in dSPE were optimized. Application
      of the developed method to the analysis of spiked Milli-Q, mineral, tap, and
      wastewater samples resulted in good recoveries values ranging from 62.3 to 116%
      with relative standard deviation values lower than 7.7% in all cases. Limits of
      detection were in the range of 28-94 ng/L. The proposed method is very fast,
      simple, repeatable, accurate and highly selective.

PMID- 21726876
TI  - Capillary electrophoresis with LED-induced native fluorescence detection for
      determination of isoquinoline alkaloids and their cytotoxicity in extracts of
      Chelidonium majus L.
AB  - In this study, we introduced a simple and sensitive method of capillary
      electrophoresis with ultraviolet light-emitting diode-induced native fluorescence
      (UV-LEDIF) detection for the determination of isoquinoline alkaloids in extracts
      of Chelidonium majus L. Samples were extracted with acidic methanol and the
      extracts were directly analysed by CE. Simultaneous determination of protopine,
      chelidonine, coptisine, sanguinarine, allocryptopine, chelerythrine and stylopine
      was performed in 20mM phosphate buffer (pH 3.1). The baseline separation of these
      alkaloids was finished within 20 min. As these alkaloids have native
      fluorescence, they were directly detected using the commercially available UV
      light emitting diode without troublesome fluorescent derivatisation. Satisfactory
      LOD values were obtained for the studied compounds considering their appearance
      in natural extracts. Lower limits of detection were 0.05 MUg/mL for protopine,
      0.06 MUg/mL for stylopine and allocryptopine, 0.07 MUg/mL for chelidonine, 0.22
      MUg/mL for sanguinarine, 1.7 MUg/mL for chelerythrine and 5.5 MUg/mL for
      coptisine. The developed method was successfully applied to determine the
      contents of seven alkaloids in the aerial parts of Chelidonium majus L, which
      varied from 0.025 to 0.763% (w/w). Also, to demonstrate the potential of the
      proposed CE method, an estimation of the cytotoxic properties of selected
      Celandine alkaloids in a natural extract was carried out.

PMID- 21726877
TI  - The influence of the memory effect on preparative separations using the amylose
      tris(3,5-dimethylphenylcarbamate) stationary phase.
AB  - Acid/base mobile phase modifiers affect enantioseparations in ways that are not
      yet understood for the lack of systematic studies, which makes the scale-up of
      preparative separations difficult to predict. Shifts of the selectivity of
      certain pairs of enantiomers upon exposure of the column to these modifiers is
      amply documented. Furthermore, once the modifier has been removed from the mobile
      phase, the improved selectivity remains, this phenomenon has been named the
      memory effect. We selected four enantiomeric pairs for a systematic study of this
      memory effect. The selectivity of 4-chlorophenylalanine ethyl ester (4CPEE)
      improves after a solution of ethanesulfonic acid (ESA) is percolated through the
      column. The selectivity of propranolol HCl and Troger's base increases after a
      solution of diiospropylethylamine is percolated through the column. The
      selectivity of these three pairs of enantiomers is inversely affected by
      percolation of the opposite acid/base solution. Each of these four compounds
      reached an equilibrium concentration that maintained the separation of the
      enantiomeric pairs. In contrast, the selectivity of trans-stilbene oxide (TSO) is
      not affected by either acid/base modifier. Preparative separations can be used to
      detect changes in the active surface of the chiral polymer stationary phase by
      measuring the change in selectivity and resolution when modifiers are used.
      Preparative method development was carried out on analytical columns and scale-up
      to 1cm ID columns were performed in this study.

PMID- 21726878
TI  - The effect of FTY720 in the Theiler's virus model of multiple sclerosis.
AB  - FTY720 (fingolimod) has demonstrated efficacy in multiple sclerosis (MS). We
      evaluated the effects of FTY720 on progressive disability, viral load, and
      antibody responses in mice infected with Theiler's murine encephalomyocarditis
      virus (TMEV). FTY720 and phosphorylated FTY720 (FTY720-P) were detected in the
      brain after intraperitoneal injection of the drug. Bioactivity of FTY720 was
      confirmed by reduced numbers of mononuclear cells in the spleen and blood after
      treatment. No significant differences were found in disability progression, viral
      load, and serum antibody responses between the FTY720-treated versus the PBS
      treated mice. There was less production of IgG within the CNS in the FTY-treated
      group on some measures.

PMID- 21726879
TI  - Unilateral parotid electron beam radiotherapy as palliative treatment for
      sialorrhea in amyotrophic lateral sclerosis.
AB  - When ALS patients experience oropharyngeal weakness, sialorrhea can become a
      considerable challenge. Drooling has a profound negative impact in patient's
      quality of life causing embarrassing social situations. Several therapeutic
      modalities, including anticholinergic drugs, botulinum toxin injection, and
      radiotherapy have emerged as treatments for drooling in ALS. This retrospective
      case series study examined the effect of palliative radiotherapy in controlling
      problematic oral secretions in 10 ALS patients refractory to medical management.
      External electron beam radiation was targeted to a single parotid gland
      unilaterally with a total dose of 1500 cGy in 3 fractions at a depth determined
      by CT scanning. One patient received additional radiotherapy to the contralateral
      parotid due to persistent secretions. All patients reported improvement with a
      reduction in the intensity and amount of drooling. In 5 of 10 patients,
      anticholinergics were discontinued and were reduced in another two. There were no
      major side effects of treatment. We conclude that unilateral parotid electron
      radiotherapy provides satisfactory relief from sialorrhea in ALS patients and
      should be considered as a therapeutic option for patients who are refractory to
      medical management.

PMID- 21726880
TI  - Metabolite profiling of Arabidopsis seedlings in response to exogenous sinalbin
      and sulfur deficiency.
AB  - In order to determine how plant uptake of a sulfur-rich secondary metabolite,
      sinalbin, affects the metabolic profile of sulfur-deficient plants, gas
      chromatography time-of-flight mass spectrometry (GC-TOF-MS), in combination with
      liquid chromatography-mass spectrometry (LC-MS), was used to survey the
      metabolome of Arabidopsis seedlings grown in nutrient media under different
      sulfur conditions. The growth media had either sufficient inorganic sulfur for
      normal plant growth or insufficient inorganic sulfur in the presence or absence
      of supplementation with organic sulfur in the form of sinalbin (p
      hydroxybenzylglucosinolate). A total of 90 metabolites were identified by GC-TOF
      MS and their levels were compared across the three treatments. Of the identified
      compounds, 21 showed similar responses in plants that were either sulfur
      deficient or sinalbin supplemented compared to sulfur-sufficient plants, while 12
      metabolites differed in abundance only in sulfur-deficient plants. Twelve
      metabolites accumulated to higher levels in sinalbin-supplemented than in the
      sulfur-sufficient plants. Secondary metabolites such as flavonol conjugates,
      sinapinic acid esters and glucosinolates, were identified by LC-MS and their
      corresponding mass fragmentation patterns were determined. Under sinalbin
      supplemented conditions, sinalbin was taken up by Arabidopsis and contributed to
      the endogenous formation of glucosinolates. Additionally, levels of flavonol
      glycosides and sinapinic acid esters increased while levels of flavonol
      diglycosides with glucose attached to the 3-position were reduced. The
      exogenously administered sinalbin resulted in inhibition of root and hypocotyl
      growth and markedly influenced metabolite profiles, compared to control and
      sulfur-deficient plants. These results indicate that, under sulfur deficient
      conditions, glucosinolates can be a sulfur source for plants. This investigation
      defines an opportunity to elucidate the mechanism of glucosinolate degradation in
      vivo.

PMID- 21726881
TI  - Effects of sterol-binding agent nystatin on wheat roots: the changes in membrane
      permeability, sterols and glycoceramides.
AB  - Plant sterols are important multifunctional lipids, which are involved in
      determining membrane properties. Biophysical characteristics of model lipid and
      isolated animal membranes with altered sterol component have been intensively
      studied. In plants however, the precise mechanisms of involvement of sterols in
      membrane functioning remain unclear. In present work the possible interactions
      between sterols and other membrane lipids in plant cells were studied. A useful
      experimental approach for elucidating the roles of sterols in membrane activity
      is to use agents that specifically bind with endogenous sterols, for example the
      antibiotic nystatin. Membrane characteristics and the composition of membrane
      lipids in the roots of wheat (Triticum aestivum L.) seedlings treated with
      nystatin were analyzed. The application of nystatin greatly increased the
      permeability of the plasma membrane for ions and SH-containing molecules and
      decreased the total sterol level mainly as a consequence of a reduction in the
      amount of beta-sitosterol and campesterol. Dynamic light-scattering was used to
      confirm the in vitro formation of stable complexes between nystatin and beta
      sitosterol or cholesterol. Sterol depletion was accompanied by a significant rise
      in total glycoceramide (GlCer) content after 2h treatment with nystatin. Analysis
      of the GlCer composition using mass spectrometry with electrospray ionization
      demonstrated that nystatin induced changes in the ratio of molecular species of
      GlCer. Our results suggest that changes in the sphingolipid composition can
      contribute to the changes in plasma membrane functioning induced by sterol
      depletion.

PMID- 21726883
TI  - National men's health policies in Ireland and Australia: what are the challenges
      associated with transitioning from development to implementation?
AB  - The recent publication of national men's health policies in Ireland and Australia
      marks the first attempts by state governments anywhere in the world to target men
      as a specific population group for the strategic planning of health. The impetus
      for policy action in both countries can be traced to an increasing concern about
      sex differences in health status between men and women; a growing awareness of
      the need for a more gender-specific approach to health policy; and an expanding
      men's health field at a research, advocacy and community/voluntary level. This
      paper will describe the background to men's health policy development in Ireland
      and Australia; outline the aims, methodologies and key principles used for policy
      development; and highlight the principal priorities for policy action. It will
      pay particular attention to the challenges associated with transitioning from
      policy development to implementation, and reflect on some of the key lessons
      learned to date.

PMID- 21726882
TI  - The pre-adoption demographic and health profiles of men participating in a
      programme of men's health delivered in English Premier League football clubs.
AB  - OBJECTIVES: To investigate the pre-adoption demographic and health profiles of
      men participating in a programme of men's health delivered in English Premier
      League (EPL) football clubs. STUDY DESIGN: A series of match day and programmed
      health promotion interventions held in EPL clubs (n = 16), including awareness
      raising activity days for supporters, weekly healthy lifestyle classes, and
      outreach activities targeted in local communities. Interventions were delivered
      at football stadia, club training venues and community facilities. Interventions
      were run by health trainers who received specific training in men's health and
      behavioural change activities. METHODS: Participants completed self-report
      measures for demographics and lifestyle behaviours, including physical activity,
      consumption of fruit and vegetables, smoking, height, weight, consumption of
      alcohol and perception of health. Measurement occurred before the interventions.
      Data were independently analysed and used to assess adoption of the interventions
      and pre-intervention health profiles of participants. RESULTS: Nine hundred and
      forty-six men adopted the interventions, but the mode of engagement led to
      variations in the sample size. Demographics showed that 89% (n = 783/875) were
      aged 18-44 years and 78% (n = 685/878) were White British. In a subsample, the
      percentages of men failing to meet health guidelines were as follows: physical
      activity, 79% (n = 351/440); consumption of fruit and vegetables, 82% (n =
      315/380); smoking, 28% (n = 103/373); high body weight, 67% (n = 245/358); and
      high alcohol consumption, 40% (n = 112/279). Sixty-nine percent of men (n =
      242/348) considered that they had no health problems, but 67% (n = 208/310)
      presented with three or more risk factors for coronary heart disease. Over 40% (n
      = 125/307) reported never going to see their general practitioner. CONCLUSION: A
      national programme of men's health promotion interventions delivered in EPL
      football clubs was effective in reaching target audiences. Interventions were
      predominantly adopted by men not meeting health guidelines.

PMID- 21726884
TI  - Screening for methicillin-resistant staphylococci in dogs admitted to a
      veterinary teaching hospital.
AB  - This study investigated the nasal carriage of methicillin-resistant staphylococci
      (MRS) in dogs (n=177) prior to medical examination or surgery in a veterinary
      teaching hospital. Nasal swab samples were collected after induction of
      anaesthesia and incubated overnight in salt enriched trypticase-soy broth.
      Cultures were analysed on two different agar media containing cefoxitin.
      Suspected MRS isolates were genotypically identified and characterised by
      antimicrobial susceptibility testing and staphylococcal cassette chromosome mec
      (SCCmec)-typing. Methicillin-resistant Staphylococcus aureus (MRSA) isolates were
      additionally characterised by spa-typing and multilocus sequence typing. The
      presence of Panton-Valentine leukocidin (pvl) genes was determined by PCR. MRS
      carriage was compared between animals with or without an infectious process. Two
      MRSA were isolated, both belonging to typical Belgian human hospital clones and
      lacking pvl. Additionally a methicillin-resistant Staphylococcus haemolyticus
      carrying a type V SCCmec was detected. No relationship was observed between MRS
      carriage and presence of infections. The results suggest that MRS are present in
      dogs originating from the community, albeit at a low prevalence. This could pose
      risks for cross contamination of dogs and their owners.

PMID- 21726885
TI  - [Toxic leucoencephalopathy after use of sniffed heroin, an unrecognized form of
      beneficial evolution].
AB  - INTRODUCTION: Serious leukoencephalopathy can be related to heroin injection or
      inhalation. OBSERVATION: We report the first case of leukoencephalopathy observed
      three weeks after a 46-year-old man sniffed heroin. The clinical presentation
      included cognitive and behaviour disorders, pyramidal irritation and slight gait
      instability. Blood and cerebrospinal fluid analyse were normal. Brain magnetic
      resonance imaging showed diffuse, symmetrical supratentorial white matter lesions
      producing high intense signals on FLAIR and b1000-weighted sequences. Proton
      spectroscopy revealed an increased rate of cholin, in favour of active
      demyelinated lesions. Brain biopsy showed intramyelinic oedema with reactive
      gliosis. After two and a half years, moderate attentional fluctuations and
      difficulties in initiating activities persisted. Repeated MRI showed a reduction
      of the leukoencephalopathy. CONCLUSION: Heroin could be a cause more common than
      thought of leukoencephalopathy. The clinical and radiological expression and
      prognosis could be related to the mode of consummation (inhalation, intravenous
      injection, sniffing). This parameter may modulate severity and localization of
      brain lesions. More systematic use of MRI for patients with psychiatric symptoms
      after heroin intoxications could lead to a better evaluation of heroin-related
      neurotoxicity and potentially improve prevention.

PMID- 21726886
TI  - Effects of UVA irradiation, aryl azides, and reactive oxygen species on the
      orthogonal inactivation of the human immunodeficiency virus (HIV-1).
AB  - Previously we reported that hydrophobic aryl azides partition into hydrophobic
      regions of the viral membrane of enveloped viruses and inactivate the virus upon
      UVA irradiation for 2 min. Prolonged irradiation (15 min) resulted in viral
      protein aggregation as visualized via Western blot analysis, due to reactive
      oxygen species (ROS) formation, with preservation of the surface antigenic
      epitopes. Herein, we demonstrate that these aggregates show detergent resistance
      and that this property may be useful towards the creation of a novel orthogonal
      virus inactivation strategy for use in preparing experimental vaccines. When ROS
      modified HIV virus preparations were treated with 1% Triton X-100, there was an
      increase in the percent of viral proteins (gp41, p24) in the viral pellet after
      ultracentrifugation through sucrose. Transmission electron microscopy (TEM) of
      these detergent-resistant pellets shows some recognizable virus fragments, and
      immunoprecipitation studies of the gp41 aggregates suggest the aggregation is
      covalent in nature, involving short-range interactions.

PMID- 21726887
TI  - Accuracy and precision of Legionella isolation by US laboratories in the ELITE
      program pilot study.
AB  - A pilot study for the Environmental Legionella Isolation Techniques Evaluation
      (ELITE) Program, a proficiency testing scheme for US laboratories that culture
      Legionella from environmental samples, was conducted September 1, 2008 through
      March 31, 2009. Participants (n=20) processed panels consisting of six sample
      types: pure and mixed positive, pure and mixed negative, pure and mixed variable.
      The majority (93%) of all samples (n=286) were correctly characterized, with
      88.5% of samples positive for Legionella and 100% of negative samples identified
      correctly. Variable samples were incorrectly identified as negative in 36.9% of
      reports. For all samples reported positive (n=128), participants underestimated
      the cfu/ml by a mean of 1.25 logs with standard deviation of 0.78 logs, standard
      error of 0.07 logs, and a range of 3.57 logs compared to the CDC re-test value.
      Centering results around the interlaboratory mean yielded a standard deviation of
      0.65 logs, standard error of 0.06 logs, and a range of 3.22 logs. Sampling
      protocol, treatment regimen, culture procedure, and laboratory experience did not
      significantly affect the accuracy or precision of reported concentrations.
      Qualitative and quantitative results from the ELITE pilot study were similar to
      reports from a corresponding proficiency testing scheme available in the European
      Union, indicating these results are probably valid for most environmental
      laboratories worldwide. The large enumeration error observed suggests that the
      need for remediation of a water system should not be determined solely by the
      concentration of Legionella observed in a sample since that value is likely to
      underestimate the true level of contamination.

PMID- 21726888
TI  - Comparison of endotoxin levels and gram-negative bacteria under different
      conditions in microbial laboratories and a biowaste site.
AB  - In this study, we assessed airborne endotoxin levels in university laboratories,
      hospital diagnostic laboratories, and a biowaste site. We also investigated
      indoor and outdoor sampling, sampling site, type of ventilation system, presence
      of open biowaste boxes, weather, and detection of Gram-negative bacteria (GNB). A
      total of 69 air samples were collected from 11 facilities in three institutions.
      Average total airborne endotoxin levels ranged from <0.01 to 10.02 EU m(-3), with
      an overall mean of 1.03 EU m(-3). Endotoxin levels were high in window-ventilated
      facilities, in facilities in which GNB were detected; levels were also high when
      it was rainy (all ps<0.05). Endotoxin levels were significantly correlated with
      humidity (r=0.70, p<0.01). The presence of HVAC; humidity; and the presence of
      open biowaste boxes affect endotoxin levels in laboratories.

PMID- 21726889
TI  - Evaluation of atmospheric sources of PCDD/Fs, PCBs and PBDEs around a steel
      industrial complex in northeast China using passive air samplers.
AB  - The concern about emissions of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) polychlorinated biphenyls (PCBs), and polybrominated
      diphenyl ethers (PBDEs) from steel industrial parks has increased in the past
      decades. In this study, polyurethane foam (PUF)-disk based passive air samples
      were collected in and around a big steel industrial park of Anshan, Northeast
      China from June 2008 to March 2009. The levels, seasonal variations and potential
      sources of PCDD/Fs, PCBs and PBDEs in the atmosphere around the steel industrial
      complex were investigated, and potential contribution of these three groups of
      persistent organic pollutants (POPs) from iron and steel production was also
      assessed. The air concentrations of ?(17)PCDD/Fs (summer: 0.02-2.77 pg m(-3);
      winter: 0.20-9.79 pg m(-3)), ?(19)PCBs (summer: 23.5-155.8 pg m(-3); winter: 14.6
      81.3 pg m(-3)) and ?(13)PBDEs (summer: 2.91-10.7 pg m(-3); winter: 1.10-3.89 pg
      m(-3)) in this targeted industrial park were relatively low in comparison to
      other studies, which implied that the industrial activities of iron and steel had
      not resulted in serious contamination to the ambient air in this area. On the
      whole, the air concentrations of PCDD/Fs in winter were higher than those of
      summer, whereas the concentrations of PCBs and PBDEs showed opposite trends. The
      result from principal component analysis indicated that coal combustion might be
      the main contributor of PCDD/F sources in this area.

PMID- 21726890
TI  - Organochlorine concentrations in franciscana dolphins, Pontoporia blainvillei,
      from Brazilian waters.
AB  - Blubber samples were collected from ten franciscana dolphins either incidentally
      captured in fishing operations or stranded on Sao Paulo (SP) and Parana (PR)
      states littoral, Southeastern and Southern Brazilian coast, respectively.
      Determination of PCB, DDT and HCB concentrations were performed by capillary gas
      chromatograph coupled to electron capture detector (ECD). SigmaDDT, SigmaPCB and
      HCB concentrations ranged from 264 ng g(-1) to 5811 ng g(-1) lipid, from 909 ng
      g(-1) to 5849 ng g(-1) lipid and from 10 ng g(-1) to 61 ng g(-1) lipid,
      respectively. Regarding DDTs, the distribution of the mean percentages decreased
      in the following order: p,p'-DDE>p,p'-DDD>p,p'-DDT. The SigmaDDT/SigmaPCB ratio
      varied between 0.27 and 0.42 in Northern and Central SP coast, while in Southern
      SP and PR coast the values were 1.6 and 1.9, respectively. Dissimilarities in
      SigmaDDT/SigmaPCB ratios point to different sources of organochlorine compounds
      to franciscana dolphins in the study area. Considering the endocrine disruptive
      action of organochlorine compounds, the concentrations found in franciscana
      dolphins from Brazilian waters may represent an additional obstacle to the
      conservation of this endangered cetacean species.

PMID- 21726891
TI  - Molten salt oxidation: a versatile and promising technology for the destruction
      of organic-containing wastes.
AB  - Molten salt oxidation (MSO), a robust thermal but non-flame process, has the
      inherent capability of destroying organic constituents in wastes, while retaining
      inorganic and radioactive materials in situ. It has been considered as an
      alternative to incineration and may be a solution to many waste disposal
      problems. The present review first describes the history and development of MSO,
      as well as design and engineering details, and then focuses on reaction
      mechanisms and its potential applications in various wastes, including hazardous
      wastes, medical wastes, mixed wastes, and energetic materials. Finally, the
      current status of and prospects for the MSO process and directions for future
      research are considered.

PMID- 21726892
TI  - Air quality assessment by tree bark biomonitoring in urban, industrial and rural
      environments of the Rhine Valley: PCDD/Fs, PCBs and trace metal evidence.
AB  - Tree barks were used as biomonitors to evaluate past atmospheric pollution within
      and around the industrial zones of Strasbourg (France) and Kehl (Germany) in the
      Rhine Valley. The here estimated residence time for trace metals, PCBs and
      PCDD/Fs in tree bark is >10 years. Thus, all pollution observed by tree bark
      biomonitoring can be older than 10 years. The PCB baseline concentration (sum of
      seven PCB indicators (Sigma(7)PCB(ind))) determined on tree barks from a remote
      area in the Vosges mountains is 4 ng g(-1) and corresponds to 0.36 * 10(-3)ng
      toxic equivalent (TEQ) g(-1) for the dioxin-like PCBs (DL-PCBs). The northern
      Rhine harbor suffered especially from steel plant, waste incinerator and thermal
      power plant emissions. The polychlorinated dibenzo-p-dioxin and dibenzofuran
      (PCDD/Fs) concentrations analyzed in tree barks from this industrial area range
      between 392 and 1420 ng kg(-1) dry-weight (dw) corresponding to 3.9 ng
      TEQ(PCDD/Fs) kg(-1) to 17.8 ng TEQ(PCDD/Fs) kg(-1), respectively. Highest PCDD/F
      values of 7.2 ng TEQ kg(-1) to 17.8 ng TEQ kg(-1) have been observed close to and
      at a distance of <2 km southwest of the chemical waste incinerator. However, very
      close to this incinerator lowest TEQ dioxin-like PCB (TEQ(DL-PCB)) values of
      0.006 ng TEQ g(-1) have been found. On the other hand close to and southwest and
      northeast of the steel plant the values are comparatively higher and range
      between 0.011 ng TEQ g(-1) and 0.026 ng TEQ g(-1). However, even stronger
      Sigma(7)PCB(ind) enrichments have been observed at a few places in the city
      center of Kehl, where SigmaDL-PCB values of up to 0.11 ng TEQ g(-1) have been
      detected. These enrichments, however, are the result of ancient pollutions since
      recent long-term measurements at the same sites indicate that the atmospheric PCB
      concentrations are close to baseline. Emissions from an old landfill of waste
      and/or great fires might have been the reasons of these PCB enrichments. Other
      urban environments of the cities of Kehl and Strasbourg show significantly lower
      Sigma(7)PCB(ind) concentrations. They suffer especially from road and river
      traffic and have typically Sigma(7)PCB(ind) concentrations ranging from 11 ng g(
      1) to 29 ng g(-1). The PCB concentration of 29 ng g(-1) has been found in tree
      bark close to the railway station of Strasbourg. Nevertheless, the corresponding
      TEQ(DL-PCB) are low and range between 0.2 * 10(-3) ng TEQ g(-1) and 7 * 10(-3) ng
      TEQ g(-1). Samples collected near road traffic are enriched in Fe, Sb, Sn and Pb.
      Cd enrichments were found close to almost all types of industries. Rural
      environments not far from industrial sites suffered from organic and inorganic
      pollution. In this case, TEQ(DL-PCB) values may reach up to 58 * 10(-3) ng TEQ g(
      1) and the corresponding V, Cr, Co, Ni, and Cd concentrations are comparatively
      high.

PMID- 21726893
TI  - Which persistent organic pollutants can we map in soil using a large spacing
      systematic soil monitoring design? A case study in Northern France.
AB  - Persistent organic pollutants (POPs) impact upon human and animal health and the
      wider environment. It is important to determine where POPs are found and the
      spatial pattern of POP variation. The concentrations of 90 molecules which are
      members of four families of POPs and two families of herbicides were measured
      within a region of Northern France as part of the French National Soil Monitoring
      Network (RMQS: Reseau de Mesures de la Qualite des Sols). We also gather
      information on five covariates (elevation, soil organic carbon content, road
      density, land cover and population density) which might influence POP
      concentrations. The study region contains 105 RMQS observation sites arranged on
      a regular square grid with spacing of 16 km. The observations include hot-spots
      at sites of POP application, smaller concentrations where POPs have been
      dispersed and observations less than the limit of quantification (LOQ) where the
      soil has not been impacted by POPs. Fifty nine of the molecules were detected at
      less than 50 sites and hence the data were unsuitable for spatial analyses. We
      represent the variation of the remaining 31 molecules by various linear mixed
      models which can include fixed effects (i.e. linear relationships between the
      molecule concentrations and covariates) and spatially correlated random effects.
      The best model for each molecule is selected by the Akaike Information Criterion.
      For nine of the molecules, spatial correlation is evident and hence they can
      potentially be mapped. For four of these molecules, the spatial correlation
      cannot be wholly explained by fixed effects. It appears that these molecules have
      been transported away from their application sites and are now dispersed across
      the study region with the largest concentrations found in a heavily populated
      depression. More complicated statistical models and sampling designs are required
      to explain the distribution of the less dispersed molecules.

PMID- 21726894
TI  - Promoter methylation analysis of WNT/beta-catenin signaling pathway regulators to
      detect adenocarcinoma or its precursor lesion of the cervix.
AB  - OBJECTIVE: Cervical adenocarcinoma (AdCA) and adenocarcinoma in situ (ACIS) are
      frequently missed in cytology-based screening programs. Testing for high-risk
      human papillomavirus (hrHPV) improves their detection, but novel ACIS/AdCA
      specific biomarkers are needed to increase specificity for these lesions. Novel
      markers may be deduced from the WNT/beta-catenin signaling pathway, which is
      aberrantly activated during cervical carcinogenesis. METHODS: Promoter
      methylation of nine WNT-antagonists (APC, AXIN2, DKK3, SFRP2, SFRP4, SFRP5,
      SOX17, WIF1 and WNT5A) was evaluated by methylation-specific PCR (MSP) on a small
      series of cervical tissue specimens, including AdCA and SCC. To estimate the
      diagnostic potential of the genes most frequently methylated in AdCA an extended
      series of ACIS, AdCA, CIN3, SCC, and normal cervical tissue specimens (n=131) as
      well as 49 hrHPV-positive scrapings were analyzed by quantitative MSP (qMSP).
      RESULTS: The frequency of DKK3 and SFRP2 methylation was significantly higher in
      AdCA compared to SCC, i.e. 82% vs. 18% (p<0.01) and 84% vs. 39% (p<0.01),
      respectively, while SOX17 methylation frequency was significantly higher in SCC
      than AdCA, i.e. 89% vs. 62% (p<0.05). Methylation of WIF1 was common in both AdCA
      (71%) and SCC (54%). Methylation frequencies ranged from 4% to 55% in precursor
      lesions and from 0% to 5% in normal biopsies. When tested on HPV-positive
      cervical scrapings, qMSP of the best ACIS/AdCA discriminator genes, i.e. DKK3 and
      SFRP2, detected all women with underlying ACIS/AdCA, compared to 3% of controls.
      CONCLUSIONS: DKK3 and SFRP2 promoter methylation is highly indicative for the
      presence of ACIS/AdCA, thereby providing promising triage markers for HPV
      positive women at risk of ACIS/AdCA.

PMID- 21726895
TI  - The insulin-like growth factor 1 pathway is a potential therapeutic target for
      low-grade serous ovarian carcinoma.
AB  - OBJECTIVE: To validate the overexpression of insulin-like growth factor 1 (IGF-1)
      and its receptor (IGF-1R) in low-grade serous ovarian carcinoma (SOC), and to
      investigate whether the IGF-1 pathway is a potential therapeutic target for low
      grade SOC. METHODS: Gene expression profiling was performed on serous borderline
      ovarian tumors (SBOTs) and low-grade SOC, and overexpression of IGF-1 in low
      grade SOC was validated by RT-PCR and immunohistochemistry. The effect of
      exogenous IGF-1 on cell proliferation was determined in cell lines by cell
      proliferation assays, cell migration assays, and Western blot. Signaling pathways
      downstream of IGF-1 and the effects of the AKT inhibitor MK-2206 were
      investigated by Western blot analysis and by generating IGF-1R short hairpin RNA
      stable knockdown cell lines. Low- and high-grade cell lines were treated with the
      dual IGF-1R- and insulin receptor-directed tyrosine kinase inhibitor OSI-906, and
      cellular proliferation was measured. RESULTS: mRNA analysis and immunostaining
      revealed significantly higher IGF-1 expression in low-grade SOCs than in SBOTs or
      high-grade SOCs. In response to exogenous treatment with IGF-1, low-grade cell
      lines exhibited more intense upregulation of phosphorylated AKT than did high
      grade cell lines, an effect that was diminished with IGF-1R knockdown and MK-2206
      treatment. Low-grade SOC cell lines were more sensitive to growth inhibition with
      OSI-906 than were high-grade cell lines. CONCLUSIONS: IGF-1 is overexpressed in
      low-grade SOCs compared with SBOTs and high-grade SOCs. Additionally, low-grade
      SOC cell lines were more responsive to IGF-1 stimulation and IGF-1R inhibition
      than were high-grade lines. The IGF-1 pathway is therefore a potential
      therapeutic target in low-grade SOC.

PMID- 21726896
TI  - Prospective analysis of the transition to sexual experience and changes in sexual
      self-esteem among adolescents attending therapeutic schools.
AB  - Given increased sexual risk-taking among youth with mental health problems, this
      study sought to understand the developmental trajectory of sexual self-esteem
      (SSE) among this vulnerable population and how it is impacted by sexual
      experiences. Participants were 185 adolescents who attended
      therapeutic/alternative schools in southern New England. Changes in five domains
      of SSE identified by Zeanah and Schwarz (1996) were examined across adolescents
      who either: 1) were sexually active at baseline, 2) transitioned to activity
      during the study, and 3) remained inexperienced at follow-up. In support of the
      hypothesis that changes in SSE precede onset of experience, youth who
      transitioned reported higher baseline scores in the Skills domain than those who
      remained inexperienced. SSE was subsequently impacted by sexual activity, with
      differences in several domains found at baseline and follow-up across level of
      experience. Changes in SSE following sexual experience depended, in part, on the
      percentage of casual partners teens reported.

PMID- 21726897
TI  - Altered feeding habits and strategies of a benthic forage fish (Fundulus
      heteroclitus) in chronically polluted tidal salt marshes.
AB  - Responses in feeding ecology of a benthic forage fish, mummichogs (Fundulus
      heteroclitus), to altered prey resources were investigated in chronically
      polluted salt marshes (the Arthur Kill-AK, New York, USA). The diet niche breadth
      of the AK populations of mummichogs was significantly lower than that of the
      reference population, reflecting reduced benthic macroinfaunal species diversity.
      Most of the AK populations also had 2-3 times less food in their gut than the
      reference population. This disparity in gut fullness among the populations
      appeared to be partly due to ingested prey size shifts; some of the AK
      populations ingested fewer large prey than the reference population. Furthermore,
      benthic assemblages were strongly associated with sediment-associated mercury;
      gut fullness of the AK populations also significantly decreased with increasing
      mercury body burdens. These results indicate that chronic pollution may have
      directly (chemical bioaccumulation) and indirectly (reduced prey availability)
      altered the feeding ecology of mummichogs.

PMID- 21726898
TI  - Modulation of the immune-related gene responses to protect mice against Japanese
      encephalitis virus using the antimicrobial peptide, tilapia hepcidin 1-5.
AB  - Japanese encephalitis virus (JEV), a neurotropic flavivirus, is one of the major
      causes of acute encephalitis in humans. After infection, it is commonly
      associated with inflammatory reactions and neurological disease. There is still
      no effective antiviral drug available against Japanese encephalitis virus
      infection. Recently, a number of investigators found that antimicrobial peptide
      (AMPs) present a broad range of biological activities including antimicrobial and
      immunomodulatory activities. In this study, we found that an AMP, tilapia
      hepcidin (TH)1-5, caused no harm to either cells or test animals during the test
      course and could control JEV viral infection in BHK-21 cells. Mice co-injected
      with TH1-5/JEV and subsequently subjected to JEV re-challenge survived and
      behaved normally. The neuroprotective effects were associated with marked
      decreases in: (i) the viral load and viral replication within the brain, (ii)
      neuronal death, and (iii) secondary inflammation resulting from microglial
      activation. TH1-5 was also determined to enhance adaptive immunity by elevating
      levels of anti-JEV-neutralizing antibodies in the serum. The microarray data also
      showed that TH1-5 modulated Socs-6, interleukin (IL)-6, Toll-like receptor (TLR)
      1, TLR-7, caspase-4, interferon (IFN)-beta1, ATF-3, and several immune-responsive
      genes to protect mice against JEV infection. In addition, TH1-5 was confirmed to
      modulate the expressions of several proinflammatory and immune-responsive genes,
      such as IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-alpha,
      IFN-gamma and monocyte chemoattractant protein (MCP)-1 at both the
      transcriptional and translational levels in JEV-infected mice. In conclusion, our
      findings provide mechanistic insights into the actions of TH1-5 against JEV.
      Results from our in vivo and in vitro experiments clearly indicate that TH1-5 has
      antiviral, neuroprotective, anti-inflammatory, and immunomodulatory activities.
      Furthermore, TH1-5 successfully reduced the severity of disease induced by JEV.
      Our results point out that TH1-5 is a promising candidate for further development
      as an antiviral agent against JEV infection.

PMID- 21726899
TI  - Dual docetaxel/superparamagnetic iron oxide loaded nanoparticles for both
      targeting magnetic resonance imaging and cancer therapy.
AB  - Theragnostics polymer nanoparticles (NPs) loaded simultaneously with anticancer
      drug docetaxel (Dtxl) and superparamagnetic iron oxide (SPIO) nanocrystals were
      developed for both cancer therapy and ultrasensitive MRI. These multifunctional
      polymer vesicles were formed by carboxy-terminated poly(lactic-co-glycolic) acid
      using a single emulsion evaporation method. The active tumor-targeting single
      chain prostate stem cell antigen antibodies (scAb(PSCA)) were conjugated on the
      surface of polymer vesicles by using functional poly(ethylene glycol). The
      diameter of NPs was about 147 nm and the SPIO and drug encapsulation efficacy was
      23% and 6.02%, respectively. Vibration simple magnetometer and X-ray diffraction
      proved that the superparamagnetic behavior of SPIO was not changed during NPs
      formation and modification. The NPs exhibited a triphasic drug release pattern in
      vitro over 30 days. Enhanced cellular uptake ability and antiproliferative effect
      of the targeted NPs in prostate cancer PC3 cell line by using the confocal laser
      scanning microscopy and cytotoxicity assay were observed. Moreover, the Prussian
      blue staining and the MRI assay in vitro demonstrated that the NPs have a high
      SPIO clustering effect. Therefore, these stable and tumor-targeting polymer NPs
      could be promising multifunctional vesicles for simultaneous targeting imaging,
      drug delivery and real time monitoring of therapeutic effect.

PMID- 21726900
TI  - Expression patterns of Notch receptors and their ligands Jagged and Delta in
      human placenta.
AB  - The establishment of an appropriate fetomaternal vessel system is a prerequisite
      for prevention of pregnancy associated pathologies. Notch receptors and ligands
      are manifoldly involved in vascular development and angiogenesis. To further
      characterize the process of human placental vasculo- and angiogenesis we
      investigated the expression pattern of Notch receptors and their ligands during
      pregnancy. Real time RT-PCR, immunohistochemistry and flow cytometry analysis
      were performed in early (6-12) weeks of gestation (w.o.g.) and late placenta (37
      41 w.o.g.). To specify the exact cellular localization immunofluorescent
      labelling of epithelial and endothelial cells (EC), respectively, with
      cytokeratin-7 and vonWillebrand factor (vWF) was done. One placenta from a
      patient with Alagille syndrome (AGS) was examined with real time RT-PCR and
      immunohistochemistry. The receptors Notch2, -3, -4 and their ligands Jagged1, -2
      and Delta1, -4 were detected at both the mRNA and protein level in early and late
      placenta. Notch1 was only detected at protein level. The expression was found
      mainly in the stromal compartment: placental EC expressed Notch1, Delta4, Jagged1
      and Delta1. A strong Jagged1 expression was found in the endothelium of arteries
      and veins supporting a role in differentiation of capillaries. Hofbauer cells
      (HC) primarily displayed the receptors Notch2, -3 and -4. Placental stromal cells
      (SC) were positive for Jagged2. The syncytiotrophoblast (ST) and cytotrophoblast
      (CT) cells revealed a weak but detectable co-localization with cytokeratin-7 and
      Notch1, -3 and Delta1. These results were verified by flow cytometry of freshly
      isolated placental cells of placental tissue. Interestingly Jagged1 expression
      was absent in endothelial cells from an AGS placenta. The Notch receptors and
      their ligands are expressed in human placental ST, CT, EC, SC and HC. The
      distribution pattern of Notch receptors and their ligands suggests their
      involvement in the process of placental vasculo- and angiogenesis via cell-cell
      communication between trophoblast, -stroma and endothelial cells.

PMID- 21726901
TI  - Interrelationships between cadmium, zinc and antioxidants in the liver of the rat
      exposed orally to relatively high doses of cadmium and zinc.
AB  - Zinc (Zn) reduces cadmium (Cd)-induced toxicity in the liver although it
      increases Cd tissue burden in some conditions; hence, the present study is
      designed to study the relationships between Cd, Zn and antioxidants in the liver
      of rats exposed to Cd. Livers of male rats which received orally relatively high
      doses of Cd (200 mg Cd/L as Cd chloride or Cd (200 mg/L)+Zn (500 mg Zn as Zn
      chloride) during five weeks, were investigated. Cd induced an accumulation of Cd
      and Zn in parallel to depletion in important variables (GSH, GSH/GSSG, CuZn-SOD
      and GPx activities) and to elevation in others (Cd/Zn and GSSG). Cd, did not
      affect CuZn SOD/GPx, nor Mn-SOD in the liver. Cd accumulation, Cd/Zn, CuZn SOD
      activity and CuZn SOD/GPx, was increased remarkably under Zn action. Zn supply
      ameliorated GSH level and partially reversed the decrease in GSH/GSSG, but it did
      not ameliorate GPx activity. Analysis showed high correlations between Cd and the
      majority of the variables, while Zn was positively correlated with only GSSG. We
      suggest from our results that Zn has indirect ameliorative effects on Cd-induced
      toxicity in the liver and that the increase in Cd retention is probably the key
      mechanism modulating, in the case of relatively high doses of Cd, the antioxidant
      response during exposure to Cd and Zn.

PMID- 21726902
TI  - [Superficial siderosis, an underestimated entity].
AB  - OBJECTIVE: To review the clinical and MRI aspects in a series of cases with
      superficial siderosis of the central nervous system. METHODS: We retrospectively
      reviewed the patients with imaging evidence of superficial siderosis,
      investigated in two radiological centers between January 2006 and January 2010.
      The patients with aneurysms or arterio-venous malformations were excluded from
      this study. RESULTS: Cortical hemosiderin deposits were present in 25 (0.2%) of
      the 5904 MRIs with a T2-weighted gradient echo sequence. The classic association
      bilateral hypoacousia, ataxia and pyramidal signs were rarely found (two cases -
      8%). Seven patients (28%) had a bilateral hearing impairment, seven (28%) a
      cerebellar syndrome and two (8%) a pyramidal syndrome. Sixteen patients (64%) had
      only supratentorial hemosiderin deposits. A cause of subarachnoid bleeding was
      identified in 76% of cases: amyloid angiopathy (40%), trauma (16%), cranio-spinal
      surgery (8%), cavernomas (8%) and brain tumors (4%). CONCLUSION: Superficial
      siderosis seems to be more frequent than previously thought. The classic clinical
      triad is rare, although the asymptomatic cases are frequent. A source of
      subarachnoid bleeding is generally found. Amyloid angiopathy is a frequent
      etiology of superficial siderosis in elderly patients. In the absence of other
      causes of subarachnoid bleeding, superficial siderosis may become a magnetic
      resonance marker for amyloid angiopathy.

PMID- 21726903
TI  - Induction of circulating monocyte chemoattractant protein-1 in women with
      gonadotropin-releasing hormone agonist.
AB  - The aim of the present study was to determine the influence of acute estrogen
      deficiency induced by administration of a gonadotropin-releasing hormone (GnRH)
      agonist on circulating levels of cytokines and chemokines. Eighty-three women
      with uterine leiomyoma were assigned in open, parallel-group fashion to a no
      treatment (control) group and a GnRH-agonist group. Serum levels of nine
      cytokines and chemokines as well as vascular inflammatory markers were measured.
      Serum levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis
      factor-alpha (TNFalpha) in the GnRH-agonist group were increased significantly at
      6 months. There were also significant differences in percentage changes in
      interleukin (IL)-6, IL8, MCP1, and macrophage inflammatory protein-1beta
      (MIP1beta) between the control and GnRH agonist groups. Soluble intercellular
      adhesion molecule-1 (sICAM1) and E-selectin levels showed significant increases
      in the GnRH agonist group at 6 months. Serum MCP1 concentrations showed weak
      correlations with levels of sICAM and E-selectin. We conclude that a hypo
      estrogenic state due to administration of a GnRH agonist increases circulating
      levels of cytokines and chemokines, especially MCP1.

PMID- 21726904
TI  - Innate immune responses of temperamental and calm cattle after transportation.
AB  - The objective was to investigate measures of cellular innate immune responses
      among calm and temperamental Brahman bulls in response to handling and
      transportation. Sixteen Brahman bulls (344 +/- 37 d of age; 271.6 +/- 45.5 kg BW)
      classified as either calm (n=8) or temperamental (n=8) were loaded onto a
      trailer, transported for 4h to a novel facility, rested 16 h overnight, and then
      were returned to their original facility after a 4h transport. Blood samples were
      collected immediately prior to (time 0) and at 24, 48, and 96 h after initial
      loading for analyses of innate immune and blood parameters. Leukocyte counts did
      not differ (P>0.05) due to temperament before or after transportation, but
      neutrophil:mononuclear cell ratios were greater in temperamental bulls compared
      to calm bulls at 24h. At 24h, expression of peripheral neutrophil beta(2)
      integrin decreased among all bulls compared with 0 h (P<0.01). Temperamental
      bulls had greater glucose and cortisol than calm bulls (P<0.01) at 48 h; whereas
      calm bulls had elevated neutrophil L-selectin expression, and phagocytic and
      oxidative burst activity compared with temperamental bulls (P<0.10) at 48 h. The
      supernatant collected from endotoxin-stimulated whole blood cultures had greater
      TNF-alpha concentrations at 48 h than at the other time points (P<0.05), but no
      temperament effect was observed (P>0.05). In contrast, 96 h after initial loading
      the supernatant TNF-alpha concentrations were lower (P<0.05) among all cattle.
      Lastly, transportation increased neutrophil phagocytosis, oxidative burst, and
      cell adhesion molecule expression 96 h post-transportation and the effect was
      more pronounced among calm bulls. These data suggest that neutrophils from calm
      bulls are more likely to resist microbial invasion at 96 h after transportation
      than neutrophils from temperamental bulls.

PMID- 21726905
TI  - Time-dependent in-vivo effects of interleukin-2 on neurotransmitters in various
      cortices: relationships with depressive-related and anxiety-like behaviour.
AB  - We investigated the impact of systemically injected IL-2 (2.5 MUg/kg, i.p.) on
      serotonergic and dopaminergic neurotransmission in various cortical areas by in
      vivo microdialysis. IL-2 lastingly reduced extracellular 5-HT levels in the
      medial prefrontal (-75%), occipital (-70%), and temporal cortices (-45%), whereas
      dopamine was only moderately reduced in the medial prefrontal cortex. Based on
      the serotonergic time profile, we conducted further experiments to test for acute
      and delayed (2 h post injection) depressive-related effects of systemic IL-2 (0
      5.0 MUg/kg) in a forced swim test and delayed effects on anxiety-like behaviour
      in the elevated plus-maze. IL-2 had dose-dependent effects on depressive-related
      behaviour after delayed but not acute testing, but no effects on anxiety-like
      behaviour.

PMID- 21726906
TI  - Management of supraglottic dysgenesis presenting as laryngomalacia.
AB  - Laryngomalacia is a common source of stridor and can lead to significant upper
      airway obstruction and feeding disturbances in infants. We describe a unique case
      of supraglottic dysgenesis presenting as laryngomalacia featuring a prominent "s
      shaped" epiglottis with both posterior edges fused to the right aryepiglottic
      fold/arytenoid complex. Although this anomaly is not accounted for in any of the
      current laryngomalacia classification schemes, modified laser supraglottoplasty
      was a satisfactory approach leading to successful decannulation. Laryngeal
      embryology and possible timing of the pathogenesis of this rare occurrence are
      reviewed as well.

PMID- 21726907
TI  - The effectiveness of a self-management program on quality of life for knee
      osteoarthritis (OA) patients.
AB  - PURPOSE: To evaluate the effectiveness of the Taipei Osteoarthritis Program
      (TOAP) for community elderly persons who suffer from knee OA. METHODS: A quasi
      experimental study was conducted between January 2008 and December 2008. Two
      hundred and five community-dwelling individuals aged 67+/-10 years with knee OA
      were recruited from four districts in Taipei City and randomized. By a clustered
      randomization according to the districts, 114 participants were in the
      intervention group (IG) with a 4-week TOAP program and 91 participants were in
      the control group (CG) with routine care. The main outcome measures included
      health-related quality of life (HRQOL) and disability level, which were assessed
      by the Short Form-36 Taiwan Version (T-SF36) and the Western Ontario McMaster
      Universities Arthritis Index Taiwan Version (T-WOMAC), respectively, and were
      repeatedly measured at the baseline, post invention (4 weeks after baseline), and
      follow-up (8 weeks after baseline). RESULTS: Subjects in the IG increased their
      changes of GH scores from baseline to post-intervention and follow-up, which were
      significantly more than those of subjects in the CG (p=0.011 and 0.005,
      respectively). Significant difference of changes was also found at follow-up for
      the mental component scale between the groups (p=0.013). There was no change in
      disability level. CONCLUSIONS: The arthritis self-management program improved the
      psychological outcomes among the participants, but it had no significant effect
      on a self-reported disability level.

PMID- 21726908
TI  - Identifying patients at risk of death or hospitalisation due to worsening heart
      failure using decision tree analysis: evidence from the Trans-European Network
      Home-Care Management System (TEN-HMS) study.
AB  - OBJECTIVES: To stratify patients recently discharged from hospital with heart
      failure (HF) according to their risk of death and/or hospitalisation for
      worsening HF (WHF), to enable timely and appropriate monitoring and intervention.
      METHODS: Data from the TEN-HMS study were used in this analysis. Chi-square
      automatic interaction detector (CHAID) decision trees were constructed using a 10
      fold cross-validation to predict events at 1-year and compared with logistic
      regression (LR) models using ROC curve analysis. RESULTS: 284 patients were used
      for training and 160 patients available at 4-month for validation. Amino-terminal
      pro-brain natriuretic peptide (NT-proBNP) was the strongest predictor of
      mortality identifying groups with high (>13,492 pg/ml), medium (3127-13,492
      pg/ml) and low (<= 3127 pg/ml) risk, followed by MI, systolic blood pressure,
      age, heart rhythm, study randomisation group and serum sodium. NT-proBNP was also
      the strongest predictor for death or hospitalization for WHF identifying groups
      with high (>13,492 pg/ml), medium (584-13,492 pg/ml), and low (<= 584 pg/ml),
      followed by MI, creatinine, heart rhythm, potassium and urea. CHAID trees tended
      to perform better than LR-models (prediction of the composite outcome: ROC area
      with 95% CI, 0.797 (0.745-0.849) for CHAID and 0.738 (0.680-0.796) for LR-model;
      p=0.041; prediction of mortality: 0.892 (0.853-0.931) for CHAID and 0.858 (0.813
      0.904) for LR; p=0.15). CONCLUSIONS: Decision trees are an alternative
      classification method used to differentiate risk in patients with HF. The
      resultant models are concise, free of subjective variables and understood easily
      by clinicians. Further exploration of their potential and validation in other
      data-sets is justified.

PMID- 21726909
TI  - Atrial fibrillation, arrhythmia burden and thrombogenesis.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, which is
      associated with substantial risk of stroke and thromboembolism. The epidemiology
      and health care burden associated with AF have increased significantly, and will
      continue to rise. Until recently, the concept and/or quantification of disease
      burden in AF tended to be ignored nor its consequences recognised. However, AF
      burden can now be assessed more accurately and reliably with the aid of cardiac
      rhythm management devices. There is a lot of interest on the issue of 'how much
      AF is needed to cause thromboembolism?' and this article summarises the available
      literature on this topic, with the aim of providing a better understanding of the
      clinical importance of device-detected atrial high-rate episodes and an overview
      of arrhythmia burden on thrombogenesis and clinical thromboembolism.

PMID- 21726910
TI  - The impact of body mass index on the efficacy and safety of catheter ablation of
      atrial fibrillation.
AB  - BACKGROUND: Obesity is a well established risk factor for atrial fibrillation
      (AF) development. Our purpose was to determine the impact of body mass index
      (BMI) on the safety and efficacy of radiofrequency catheter ablation of AF.
      METHODS: Two hundred and twenty-six consecutive patients with symptomatic, drug
      refractory paroxysmal (59.3%) and persistent (40.7%) AF underwent wide
      circumferential electrical pulmonary vein isolation. Patients were classified
      according to BMI as normal (<25kg/m(2)); overweight (25 to 29.9kg/m(2)); and
      obese (>=30kg/m(2)). RESULTS: Patients with high BMI were younger and displayed a
      higher rate of hypertension, increased left atrial diameter, increased left
      ventricular end-diastolic and end-systolic diameters, and increased levels of
      several conventional markers of inflammation and oxidative stress including white
      blood cell count, fibrinogen, uric acid, alanine aminotransferase, and gamma
      glutamyltransferase (p<0.05). After a mean follow-up period of 432.32+/
      306.09days from the index procedure, AF recurrence rate was 34.9% for normal
      weight, 46.2% for overweight, and 46.2% for obese patients (p: 0.258). Subjects
      classified above the 50th percentile for BMI displayed a trend toward a higher AF
      recurrence rate (p: 0.08). In univariate Cox regression survival analysis, BMI
      was not predictive of AF recurrence. Radiation exposure was significantly higher
      in overweight and obese patients in relation to normal weight patients (p:
      0.003). No significant differences regarding major complications were observed
      among BMI groups. CONCLUSIONS: In this study population, BMI was not an
      independent predictor of AF recurrence following left atrial catheter ablation.

PMID- 21726911
TI  - Daytime sleepiness does not predict sleep apnoea in patients with coronary artery
      disease.

PMID- 21726912
TI  - Allostery in trypsin-like proteases suggests new therapeutic strategies.
AB  - Trypsin-like proteases (TLPs) are a large family of enzymes responsible for
      digestion, blood coagulation, fibrinolysis, development, fertilization, apoptosis
      and immunity. A current paradigm posits that the irreversible transition from an
      inactive zymogen to the active protease form enables productive interaction with
      substrate and catalysis. Analysis of the entire structural database reveals two
      distinct conformations of the active site: one fully accessible to substrate (E)
      and the other occluded by the collapse of a specific segment (E*). The allosteric
      E*-E equilibrium provides a reversible mechanism for activity and regulation in
      addition to the irreversible zymogen to protease conversion and points to new
      therapeutic strategies aimed at inhibiting or activating the enzyme. In this
      review, we discuss relevant examples, with emphasis on the rational engineering
      of anticoagulant thrombin mutants.

PMID- 21726913
TI  - Dosimetric consequences of rotational errors in radiation therapy of pediatric
      brain tumor patients.
AB  - PURPOSE: To quantify the rotational offsets and estimate the dose effect of
      rotation on the target volume and normal tissues in children with brain tumor.
      METHODS: Twenty-one pediatric patients with brain tumors were included in this
      study. Cone-beam CT was performed before each treatment and at the end of every
      other treatment. Translational offsets were corrected before the treatment. An
      offline analysis was performed to quantify rotational errors. The treatment plans
      were altered and recalculated to simulate a rotation of 2 degrees  and 4 degrees
      , and the dose changes were quantified. RESULTS: 1016 CBCT datasets were analyzed
      for this report. The mean of the rotations were not meaningfully different from
      zero. 18.1% of the fractions had rotations with a magnitude >=2 degrees , 5.0%
      had rotations >=3 degrees  and 0.9% had rotations >=4 degrees . For the 2 degrees
      rotational simulation, the gEUD values of the PTV and critical structures
      changed by less than 2%. For the 4 degrees  simulation, parallel type normal
      structures had minor changes (<2%), but serial type normal structures and the PTV
      had changes of 10% and 5%, respectively. CONCLUSIONS: The majority of rotational
      errors observed were less than 1 degrees . A rotational error of 2 degrees 
      produced negligible changes in the gEUD to critical structures or target volumes.
      Rotational errors >=4 degrees  produced undesirable results, therefore, at a
      minimum, errors >2 degrees  should be corrected.

PMID- 21726914
TI  - Investigations into the role of inflammation in normal tissue response to
      irradiation.
AB  - PURPOSE: Radiation-induced inflammation and production of reactive oxygen species
      (ROS) play a critical role in normal tissue response. In this study we have
      examined some aspects of these effects in lung and skin. METHODS: The superoxide
      dismutase (SOD) catalase mimetic, EUK-207, and genistein, an isoflavone with anti
      inflammatory properties, were given post-irradiation and micronuclei (MN)
      formation was determined in cells derived from irradiated lung and skin. Changes
      in breathing rate were measured using a plethysmograph following irradiation of
      C57Bl6 mice knocked out for tumor necrosis factor (TNF)-alpha or its receptors,
      TNFR1/2, or treated with endotoxin (lipopolysaccharide - LPS). RESULTS: Both EUK
      207 and genistein given after irradiation caused a large reduction in MN levels
      observed in lung cells during 14 weeks post-irradiation but ceasing treatment
      resulted in a rebound in MN levels at 28 weeks post-irradiation. In contrast,
      treatment with EUK-207 was largely ineffective in reducing MN observed in skin
      cells post-irradiation. Knock-out of TNF-alpha resulted in a reduced increase in
      breathing rate (peak at 12 weeks post-irradiation) relative to wild-type and
      TNFR1/2 knock-out. Treatment with LPS 1 h post-irradiation also reduced the
      increase in breathing rate. CONCLUSIONS: The increase in MN in lung cells after
      treatment with EUK-207 or genistein was stopped suggests that continuing ROS
      production contributes to DNA damage in lung cells over prolonged periods. That
      this effect was not seen in skin suggests this mechanism is less prominent in
      this tissue. The reduced level of radiation pneumonitis (as monitored by
      breathing rate changes) in animals knocked out for TNF-alpha suggests that this
      cytokine plays a significant role in inducing inflammation in lung following
      irradiation. The similar effect observed following LPS given post-irradiation
      suggests the possibility that such treatment modifies the long-term cyclic
      inflammatory response following irradiation in lungs.

PMID- 21726916
TI  - Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel
      endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus.
AB  - AIM: The renal and cerebral protective effects of pioglitazone were assessed in
      normoalbuminuric patients with type 2 diabetes mellitus (DM). METHODS: A total of
      68 normoalbuminuric type 2 DM patients were enrolled in a one-year open-label
      randomized controlled trial: 34 patients (pioglitazone-metformin) vs. 34 patients
      (glimepiride-metformin). All patients were assessed concerning urinary albumin:
      creatinine ratio (UACR), urinary alpha1-microglobulin, urinary beta2
      microglobulin, plasma asymmetric dymethyl-arginine (ADMA), GFR, hsC-reactive
      protein, fibrinogen, HbA1c; pulsatility index, resistance index in the internal
      carotid artery and middle cerebral artery, intima-media thickness in the common
      carotid artery; cerebrovascular reactivity was evaluated through the breath
      holding test. RESULTS: At 1 year there were differences between groups regarding
      ADMA, urinary beta2-microglobulin, urinary alpha1-microglobulin, parameters of
      inflammation, serum creatinine, GFR, UACR, the cerebral haemodynamic indices.
      Significant correlations were found between alpha 1-microglobulin-UACR
      (R(2)=0.143; P=0.001) and GFR (R(2)=0.081; P=0.01); beta2-microglobulin-UACR
      (R(2)=0.241; P=0.0001) and GFR (R(2)=0.064; P=0.036); ADMA-GFR (R(2)=0.338;
      P=0.0001), parameters of inflammation, HbA1c, duration of DM, cerebral indices.
      There were no correlations between ADMA-UACR, urinary alpha1-microglobulin and
      beta2-microglobulin. CONCLUSION: Proximal tubule (PT) dysfunction precedes
      albuminuria and is dissociated from endothelial dysfunction in patients with type
      2 DM. Pioglitazone delays PT dysfunction and improves cerebral vessels
      endothelial dysfunction in normoalbuminuric patients with type 2 DM.

PMID- 21726915
TI  - DNA double-strand break - induced pro-survival signaling.
AB  - Radiation and other types of DNA damaging agents induce a plethora of signaling
      events simultaneously originating from the nucleus, cytoplasm, and plasma
      membrane. As a result, this presents a dilemma when seeking to determine causal
      relationships and better insight into the intricacies of stress signaling. ATM
      plays critical roles in both nuclear and cytoplasmic signaling, of which, the DNA
      damage response (DDR) is the best characterized. We have recently created
      experimental conditions where the DNA damage signal alone can be studied while
      minimizing the influence from the extranuclear compartment. We have been able to
      document pro-survival and growth promoting signaling (via ATM-AKT-ERK) resulting
      from low levels of DSBs (equivalent to <=2 Gy). More extensive DSBs (>2 Gy eq.)
      result in phosphatase-mediated ERK dephosphorylation, and thus shutdown of ERK
      signaling. In contrast, radiation does not result in such dephosphorylation even
      at very high doses. We propose that phosphatases are inactivated perhaps as a
      result of reactive oxygen species, which does not occur in response to 'pure' DNA
      damage. Our findings suggest that clinically relevant radiation doses, which are
      intended to halt tumor growth and induce cell death, are unable to inhibit tumor
      pro-survival signaling via ERK dephosphorylation.

PMID- 21726918
TI  - Stereotactic body radiation therapy for lung metastases.
AB  - INTRODUCTION: Stereotactic body radiation therapy (SBRT) has an emerging role in
      patients affected with pulmonary metastases. Purpose of this study was to
      evaluate efficacy and tolerability of SBRT in a cohort of patients treated
      between 2003 and 2009 at our institution. METHODS: A total of 61 patients with
      oligometastatic lung tumors (single pulmonary nodules in 73.7%) were included in
      the study. SBRT was performed with a stereotactic body frame and a 3D-conformal
      technique. Fifty-one patients received 26 Gy in 1 fraction, 22 a dose of 45 Gy in
      3 fractions and 3 a dose of 36 Gy in 4 fractions. Primary tumor was lung cancer
      in 45.7% of patients, colorectal cancer in 21.3% and a variety of other origins
      in 33%. The primary endpoint was local control, secondary endpoints were survival
      and toxicity. RESULTS: After a median follow-up interval of 20.4 months, local
      control rates at 2 and 3 years were 89% and 83.5%, overall survival 66.5% and
      52.5%, cancer-specific survival 75.4% and 67%, progression-free survival 32.4%
      and 22.3%. Tumor volume was significantly associated to survival, with highest
      rates in patients with single small tumors. Median survival time was 42.8 months,
      while median progression-free survival time was 11.9 months. Toxicity profiles
      were good, with just one case of grade III toxicity (pneumonitis). CONCLUSION:
      This study shows that SBRT is an effective and safe local treatment option for
      patients with lung metastases. Definitive results are strictly correlated to
      clinical selection of patients.

PMID- 21726917
TI  - Promoter methylation of BRMS1 correlates with smoking history and poor survival
      in non-small cell lung cancer patients.
AB  - PURPOSE: To investigate whether methylation of BRMS1 is associated with clinical
      outcomes in patients with NSCLC. METHODS: Methylation status of BRMS1 was
      examined in 325 NSCLC patients who were treated with surgery. We analyzed
      associations between the methylation of BRMS1 genes separately and available
      epidemiologic and clinical information including smoking status, gender, age, and
      histological type, or the stage of the tumor. RESULTS: In the cohort of 325 NSCLC
      cases, 152 samples were identified as methylated (46.77%). Promoter methylation
      of BRMS1 was present only in 6 specimens (8.42%) in adjacent non-cancerous
      tissues (P=2.257 * 10(-14)). Patient smoking history had a positive correlation
      with methylation rate of BRMS1 (OR=2.508, 95%CI(1.516, 4.151)). Compared with
      unmethylated group, methylated group showed the lower level of BRMS1 mRNA
      (P=0.013). And patients with a high level of BRMS1 mRNA expression had
      significantly better overall survival than those with low expression (P=0.002).
      Multivariate Cox proportional hazard regression analysis also showed that
      promoter methylation of BRMS1 was significantly unfavorable prognostic factors
      (hazard ratio, 1.912; 95% CI, and 1.341-2.726). CONCLUSIONS: These results
      provide clinical evidence to support the notion that BRMS1 is a NSCLC metastasis
      suppressor gene. Measuring methylation status of BRMS1 promotor is a useful
      marker for identifying NSCLC patients with worse disease-free survival.

PMID- 21726919
TI  - CR1 genotype is associated with entorhinal cortex volume in young healthy adults.
AB  - Gene-brain structure associations of 3 recently discovered risk genes for
      Alzheimer's disease, CLU (rs11136000C>T), CR1 (rs6656401G>A), and PICALM
      (rs3851179G>A), were investigated in 2 independent cohorts of young healthy
      adults (n = 430 and n = 492, respectively). We assessed structural differences in
      2 core structures of Alzheimer pathology, entorhinal cortex and hippocampus, by
      voxel-based morphometry using high-resolution magnetic resonance imaging (MRI)
      data. For CLU and PICALM no significant genotype-related differences in local
      gray matter volume were found. CR1 risk allele (A) carriers showed smaller local
      gray matter volume in the entorhinal cortex, as confirmed in both cohorts. This
      association, apparent in young healthy adults, might mediate susceptibility for
      Alzheimer's disease later in life.

PMID- 21726920
TI  - [Microbiology of transplants].
AB  - Infections are one of the main complications that decisively affect the final
      outcome of transplants. Clinical microbiology laboratory has a key role in
      diagnosis, treatment and prevention of these complications. Centres with
      transplant programs must be technically supported with a well developed
      laboratory with special emphasis in rapid diagnostic techniques. In this article,
      we review the clinical background for the laboratory, its role in the evaluation
      of both donors and recipients, and the diagnostic methods for the main pathogens
      infecting transplant patients.

PMID- 21726921
TI  - Discovery of 6-substituted indole-3-glyoxylamides as lead antiprion agents with
      enhanced cell line activity, improved microsomal stability and low toxicity.
AB  - A series of highly potent indole-3-glyoxylamide based antiprion agents was
      previously characterized, focusing on optimization of structure-activity
      relationship (SAR) at positions 1-3 of the indole system. New libraries
      interrogating the SAR at indole C-4 to C-7 now demonstrate that introducing
      electron-withdrawing substituents at C-6 may improve biological activity by up to
      an order of magnitude, and additionally confer higher metabolic stability. For
      the present screening libraries, both the degree of potency and trends in SAR
      were consistent across two cell line models of prion disease, and the large
      majority of compounds showed no evidence of toxic effects in zebrafish. The
      foregoing observations thus make the indole-3-glyoxylamides an attractive lead
      series for continuing development as potential therapeutic agents against prion
      disease.

PMID- 21726922
TI  - Metronidazole prodrugs: synthesis, physicochemical properties, stability, and ex
      vivo release studies.
AB  - The aim of the present study was to develop a colon targeted delivery system for
      metronidazole using polymeric prodrug formulation. Two chitosan amide conjugates
      of metronidazole were prepared by using two different spacers to covalently link
      the drug to the amino group of the chitosan glucosamine units. Glutaric and
      succinic hemiesters of metronidazole were thus prepared and then coupled to
      chitosan to obtain metronidazole-glutaryl- and metronidazole-succinyl-chitosan
      conjugates. Polymeric prodrugs were characterized by solid state NMR method,
      namely carbon 13 cross polarization magic angle spinning ((13)C NMR CPMAS).
      Prodrug stability study was carried out in acid (pH = 1.2) and in alkaline (pH =
      7.4) buffers in a thermostatic bath at 37  degrees C. Drug release from the two
      prodrugs was studied by incubating each of them with 10% w/v cecal and colonic
      content of rats. Obtained results showed that both prodrugs were adequately
      stable in acid environment, while the succinyl conjugate was more stable than the
      glutaryl one in alkaline buffer. Both the prodrugs released the drug in cecal and
      colonic content, showing that the two systems could serve as colon specific
      delivery systems of metronidazole.

PMID- 21726923
TI  - Ecotoxicological assessment of TiO2 byproducts on the earthworm Eisenia fetida.
AB  - The increasing production of nanomaterials will in turn increase the release of
      nanosized byproducts to the environment. The aim of this study was to evaluate
      the behaviour, uptake and ecotoxicity of TiO(2) byproducts in the earthworm
      Eisenia fetida. Worms were exposed to suspensions containing 0.1, 1 and 10 mg/L
      of byproducts for 24 h. Size of TiO(2) byproducts showed aggregation of particles
      up to 700 MUm with laser diffraction. Only worms exposed at 10 mg/L showed
      bioaccumulation of titanium (ICP-AES), increasing expression of metallothionein
      and superoxide dismutase mRNA (Real-time PCR) and induction of apoptotic activity
      (Apostain and TUNEL). TiO(2) byproducts did not induce cytotoxicity on
      coelomocytes, but a significant decrease of phagocytosis was observed starting
      from 0.1 mg/L. In conclusion, bioaccumulation of byproducts and their production
      of reactive oxygen species could be responsible for the alteration of the
      antioxidant system in worms.

PMID- 21726924
TI  - Estimating mercury concentrations and fluxes in the water column and sediment of
      Lake Ontario with HERMES model.
AB  - The HERMES model-predicted Hg concentrations and fluxes in Lake Ontario were
      based on twelve lake and drainage basin variables (i.e., water temperature,
      precipitation rate, air Hg, surface area, mean depth, water volume, water inflow
      rate, inflow water Hg, inflow and lake suspended particulate matter, air-water
      and water-air mass transfer coefficients, and sedimentation rate). The HERMES
      model-predicted Hg water and surface sediment concentrations were found to be
      significantly correlated (+/-20%) with measured values (r(2) = 0.94, p < 0.0001,
      n = 13) and mechanistic model predictions (LOTOX2-Hg, r(2) = 0.95, p < 0.0001, n
      = 10). The predictive capacity of HERMES was previously tested on smaller (<=1
      km(2)) lakes in Nova Scotia and Ontario, Canada (i.e., water and sediment Hg
      concentrations were +/-15% of measured data). Results suggest that HERMES could
      be applicable to a broad range of lake sizes. Uncertainty analyses on HERMES
      model input variables indicated a larger atmospheric Hg contribution for Lake
      Ontario when compared to previous predictions for smaller lakes.

PMID- 21726925
TI  - NitroScape: a model to integrate nitrogen transfers and transformations in rural
      landscapes.
AB  - Modelling nitrogen transfer and transformation at the landscape scale is relevant
      to estimate the mobility of the reactive forms of nitrogen (N(r)) and the
      associated threats to the environment. Here we describe the development of a
      spatially and temporally explicit model to integrate N(r) transfer and
      transformation at the landscape scale. The model couples four existing models, to
      simulate atmospheric, farm, agro-ecosystem and hydrological N(r) fluxes and
      transformations within a landscape. Simulations were carried out on a theoretical
      landscape consisting of pig-crop farms interspersed with unmanaged ecosystems.
      Simulation results illustrated the effect of spatial interactions between
      landscape elements on N(r) fluxes and losses to the environment. More than 10% of
      the total N(2)O emissions were due to indirect emissions. The nitrogen budgets
      and transformations of the unmanaged ecosystems varied considerably, depending on
      their location within the landscape. The model represents a new tool for
      assessing the effect of changes in landscape structure on N(r) fluxes.

PMID- 21726926
TI  - From consent to institutions: designing adaptive governance for genomic biobanks.
AB  - Biobanks are increasingly hailed as powerful tools to advance health research.
      The social and ethical challenges associated with the implementation and
      operation of biobanks are equally well-documented. One of the proposed solutions
      to these challenges involves trading off a reduction in the specificity of
      informed consent protocols with an increased emphasis on governance. However,
      little work has gone into formulating what such governance might look like. In
      this paper, we suggest four general principles that should inform biobank
      governance and illustrate the enactment of these principles in a proposed
      governance model for a particular population-scale biobank, the British Columbia
      (BC) Generations Project. We begin by outlining four principles that we see as
      necessary for informing sustainable and effective governance of biobanks: (1)
      recognition of research participants and publics as a collective body, (2)
      trustworthiness, (3) adaptive management, and (4) fit between the nature of a
      particular biobank and the specific structural elements of governance adopted.
      Using the BC Generations Project as a case study, we then offer as a working
      model for further discussion the outlines of a proposed governance structure
      enacting these principles. Ultimately, our goal is to design an adaptive
      governance approach that can protect participant interests as well as promote
      effective translational health sciences.

PMID- 21726927
TI  - Environmental justice and health: a study of multiple environmental deprivation
      and geographical inequalities in health in New Zealand.
AB  - There is an increasing interest in the unequal socio-spatial distribution of
      environmental 'goods' and 'bads' and the associated implications for geographical
      inequalities in health. Until recently, research in this area has focused on
      solitary environmental characteristics and has been hindered by the absence of
      geographically-specific measures that recognise the multifactorial nature of the
      physical environment. However, recent work in the United Kingdom has developed an
      area-level multivariate index of health-related physical environmental
      deprivation that captures both pathogenic and salutogenic environmental
      characteristics. Applications of this index have demonstrated that, at the
      national level, multiple environmental deprivation increased as the degree of
      income deprivation rose. Further, after adjusting for key confounders, there was
      a significant association between multiple environmental deprivation and the
      health outcomes of local residents. In the current study we tested the methods
      developed in the UK to create the New Zealand Multiple Environmental Deprivation
      Index (NZ-MEDIx) for small areas across the country (n = 1860). We considered
      whether socially disadvantaged places in New Zealand had higher levels of
      multiple environmental deprivation, and if environmental disadvantage exerted an
      influence on health after adjustment for key confounders such as socioeconomic
      status. We found that although neighbourhoods with higher levels of multiple
      environmental deprivation tended to have greater social disadvantage, this
      association was not linear. Further, multiple environmental deprivation tended to
      exert a modest effect on health that was independent of the age, sex and
      socioeconomic structure of the population. These findings demonstrate that it is
      possible to develop an index of multiple environmental deprivation in an
      alternative national context which has utility in epidemiological investigations.

PMID- 21726928
TI  - Replacing GnRH agonists with GnRH antagonists in oocyte recipient cycle did not
      adversely affect the pregnancy rates.
AB  - The synchronization of the donor stimulation with the endometrial preparation of
      the recipient is usually done by downregulating the recipient's pituitary with a
      GnRH analog. OBJECTIVE: The aim of this study is to compare pregnancy and
      implantation rates among premenopausal oocyte recipients synchronized by
      pituitary suppression with GnRH agonist (Group AGO) or antagonist (Group ANTAG)
      and standard endometrial preparation with estrogen and gestagen. STUDY DESIGN:
      Prospective, observational, transversal, comparative study. Consecutive
      recipients treated at Institut Universitari Dexeus between July 2008 and December
      2009. RESULTS: One hundred and eighty-three premenopausal women were included. No
      differences were found regarding the age of donors nor the age of recipients,
      fertilization rates, number of embryos transferred and embryo quality. No
      differences were found in clinical pregnancy rates (56.1% Group AGO vs. 52.4%
      Group ANTAG). CONCLUSION: The administration of GnRH antagonists during
      endometrial preparation in oocyte recipients facilitates synchronization without
      affecting the pregnancy rate.

PMID- 21726929
TI  - MRKH syndrome with endometriosis: case report and literature review.

PMID- 21726930
TI  - Is endometrial polyp formation associated with increased expression of vascular
      endothelial growth factor and transforming growth factor-beta1?
AB  - OBJECTIVE: Endometrial polyp is a common cause of abnormal uterine bleeding, but
      the etiology and pathogenesis remain unclear. Vascular endothelial growth factor
      (VEGF) is angiogenic, related to thick walled vessels and transforming growth
      factor-beta1 (TGF-beta1) is related to fibrotic tissue, which are characteristics
      of endometrial polyps. The primary objective of this study was to find out if
      endometrial polyp formation is associated with increased expression of VEGF or
      TGF-beta1, or both. A secondary objective is to determine if the changes are
      related to steroid receptor expression. STUDY DESIGN: This prospective study
      compared VEGF and TGF-beta1 expression of endometrial polyps and adjacent
      endometrial tissue in 70 premenopausal women. The comparison of results was
      separately made for endometrium specimens obtained in the proliferative and
      secretory phases. The results were correlated with the steroid receptors
      (estrogen receptor and progesterone receptor) expression. RESULTS: The score of
      VEGF in glandular cells of endometrial polyps was significantly higher than the
      score in adjacent endometrium, both in the proliferative phase (P<0.001) and the
      secretory phase (P=0.03); the score of VEGF in stromal cells of endometrial
      polyps was significantly higher than the score in adjacent endometrium only in
      proliferative phase (P=0.006). The score of TGF-beta1 in glandular cells of
      endometrial polyps was significantly higher than the score in adjacent
      endometrium in proliferative phase (P=0.02); whereas the score of TGF-beta1 in
      stromal cells of endometrial polyps was significantly higher than the score in
      adjacent endometrium, both in the proliferative phase (P=0.006) and the secretory
      phase (P=0.008). There was a significant correlation between the expression of
      steroid receptors and VEGF and TGF-beta1 (Spearman's correlation P<0.001 and
      P<0.05, respectively). CONCLUSIONS: There was increased expression of TGF-beta1
      and VEGF in polyps compared to adjacent normal endometrial tissue. It suggested
      that these cytokines might play a role in endometrial polyp formation. In
      addition, there was a significant correlation between steroid receptor expression
      and VEGF and TGF-beta1 expression.

PMID- 21726931
TI  - Paradoxes in sexual risk-taking among non-medical related university students in
      Szeged, Hungary.

PMID- 21726932
TI  - Controlling urban air pollution caused by households: uncertainty, prices, and
      income.
AB  - We examine the control of air pollution caused by households burning wood for
      heating and cooking in the developing world. Since the problem is one of
      controlling emissions from nonpoint sources, regulations are likely to be
      directed at household choices of wood consumption and combustion technologies.
      Moreover, these choices are subtractions from, or contributions to, the pure
      public good of air quality. Consequently, the efficient policy design is not
      independent of the distribution of household income. Since it is unrealistic to
      assume that environmental authorities can make lump sum income transfers part of
      control policies, efficient control of air pollution caused by wood consumption
      entails a higher tax on wood consumption and a higher subsidy for more efficient
      combustion technologies for higher income households. Among other difficulties,
      implementing a policy to promote the adoption of cleaner combustion technologies
      must overcome the seemingly paradoxical result that efficient control calls for
      higher technology subsidies for higher income households.

PMID- 21726933
TI  - Treatment of localised renal cell carcinoma.
AB  - CONTEXT: The increasing incidence of localised renal cell carcinoma (RCC) over
      the last 3 decades and controversy over mortality rates have prompted
      reassessment of current treatment. OBJECTIVE: To critically review the recent
      data on the management of localised RCC to arrive at a general consensus.
      EVIDENCE ACQUISITION: A Medline search was performed from January 1, 2004, to May
      3, 2011, using renal cell carcinoma, nephrectomy (Medical Subject Heading [MeSH]
      major topic), surgical procedures, minimally invasive (MeSH major topic), nephron
      sparing surgery, cryoablation, radiofrequency ablation, surveillance, and
      watchful waiting. EVIDENCE SYNTHESIS: Initial active surveillance (AS) should be
      a first treatment option for small renal masses (SRMs) <4 cm in unfit patients or
      those with limited life expectancy. SRMs that show fast growth or reach 4 cm in
      diameter while on AS should be considered for treatment. Partial nephrectomy (PN)
      is the established treatment for T1a tumours (<4 cm) and an emerging standard
      treatment for T1b tumours (4-7 cm) provided that the operation is technically
      feasible and the tumour can be completely removed. Radical nephrectomy (RN)
      should be limited to those cases where the tumour is not amenable to nephron
      sparing surgery (NSS). Laparoscopic radical nephrectomy (LRN) has benefits over
      open RN in terms of morbidity and should be the standard of care for T1 and T2
      tumours, provided that it is performed in an advanced laparoscopic centre and NSS
      is not applicable. Open PN, not LRN, should be performed if minimally invasive
      expertise is not available. At this time, there is insufficient long-term data
      available to adequately compare ablative techniques with surgical options.
      Therefore ablative therapies should be reserved for carefully selected high
      surgical risk patients with SRMs <4 cm. CONCLUSIONS: The choice of treatment for
      the patient with localised RCC needs to be individualised. Preservation of renal
      function without compromising the oncologic outcome should be the most important
      goal in the decision-making process.

PMID- 21726934
TI  - Critical analysis of the relationship between sexual dysfunctions and lower
      urinary tract symptoms due to benign prostatic hyperplasia.
AB  - CONTEXT: This review focuses on the relationship among sexual dysfunction (SD),
      lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH),
      and related therapies. OBJECTIVE: We reviewed the current literature to provide
      an overview of current data regarding epidemiology and pathophysiology of SD and
      LUTS. Moreover, we analysed the impact of currently available therapies of
      LUTS/BPH on both erectile dysfunction (ED) and ejaculatory dysfunction and the
      effect of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with ED and
      LUTS. EVIDENCE ACQUISITION: We conducted a Medline search to identify original
      articles, reviews, editorials, and international scientific congress abstracts by
      combining the following terms: benign prostatic hyperplasia, lower urinary tract
      symptoms, sexual dysfunction, erectile dysfunction, and ejaculatory dysfunction.
      EVIDENCE SYNTHESIS: We conducted a comprehensive analysis of more relevant
      general population-based and BPH/LUTS or SD clinic-based trials and evaluated the
      common pathophysiologic mechanisms related to both conditions. In a further step,
      the overall impact of current BPH/LUTS therapies on sexual life, including
      phytotherapies, novel drugs, and surgical procedures, was scrutinized. Finally,
      the usefulness of PDE5-Is in LUTS/BPH was critically analysed, including
      preclinical and clinical research data as well as possible mechanisms of action
      that may contribute to the efficacy of PDE5-Is with LUTS/BPH. CONCLUSIONS:
      Community-based and clinical data demonstrate a strong and consistent association
      between LUTS and ED, suggesting that elderly men with LUTS should be evaluated
      for SD and vice versa. Pathophysiologic hypotheses regarding common basics of
      LUTS and SD as discussed in the literature are (1) alteration of the nitric oxide
      (NO)-cyclic guanosine monophosphate (cGMP) pathway, (2) enhancement of RhoA-Rho
      kinase (ROCK) contractile signalling, (3) autonomic adrenergic hyperactivity, and
      (4) pelvic atherosclerosis. The most important sexual adverse effects of medical
      therapies are ejaculation disorders after the use of some alpha-blockers and
      sexual desire impairment, ED, and ejaculatory disorders after the use of alpha
      reductase inhibitors. Minimally invasive, conventional, and innovative surgical
      treatments for BPH may induce both retrograde ejaculation and ED. PDE5-Is have
      demonstrated significant improvements in both LUTS and ED in men with BPH;
      combination therapy with PDE5-Is and alpha1-adrenergic blockers seems superior to
      PDE5-I monotherapy.

PMID- 21726935
TI  - Re: Jean-Nicolas Cornu,Geraldine Cancel-Tassin, Valerie Ondet, et Al. Olfactory
      detection of prostate cancer by dogs sniffing urine: a step forward in early
      diagnosis. Eur urol 2011; 59: 197-201.

PMID- 21726936
TI  - Hepatitis B virus X protein stimulates the Hedgehog-Gli activation through
      protein stabilization and nuclear localization of Gli1 in liver cancer cells.
AB  - Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver
      diseases, which frequently results in hepatits, cirrhosis, fibrosis, and
      ultimately hepatocellular carcinoma (HCC). Recent studies have shown the
      activation of Hedgehog signaling in HCC. Here, we provide evidences that HBV
      induces Gli-directed gene transactivation. HBx increases the protein stability of
      Gli proteins, which are key transcription factors of the Hedgehog signaling
      pathway, and nucleus translocation of Gli1 through direct protein interaction of
      HBx and Gli1. This functional synergism of Gli1 protein by HBx increases the
      Hedgehog activation-directed gene expression. Taken together, these results
      suggest that HBV infection might induce hepatocellular carcinoma by modulating
      post-translational activation of the hedgehog signaling components.

PMID- 21726937
TI  - Preoperative analysis of 11q loss using circulating tumor-released DNA in serum:
      a novel diagnostic tool for therapy stratification of neuroblastoma.
AB  - Allelic deletion of the long arm of chromosome 11 (11q loss) is closely
      associated with the prognosis of neuroblastoma (NB). Here we examined 11q loss
      using tumor-released DNA fragments in the sera of 24 cases. The allelic intensity
      score of a panel of polymorphic markers in 11q23 in serum DNA was significantly
      different between the 11q loss-positive group and the11q loss-negative group. The
      11q loss-positive and -negative groups did not overlap when a cut-off value of
      0.5 was chosen for the allelic intensity score. Our serum-based 11q loss analysis
      could predict the allelic status of 11q in tumors.

PMID- 21726938
TI  - Sensitive bioassay for detection of PPARalpha potentially hazardous ligands with
      gold nanoparticle probe.
AB  - There are so many kinds of peroxisome proliferator-activated receptor alpha
      (PPARalpha) ligands with hazardous effect for human health in the environment,
      such as certain herbicides, plasticizers and drugs. Among these agonists,
      perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and mono-(2
      ethylhexyl) phthalate (MEHP) are mostly investigated due to their persistence and
      accumulation in environment and their potential toxicity via PPARalpha. This
      investigation aims at developing a bioassay method to detect PPARalpha ligands
      based on the ligand-receptor interaction on microplate. PPARalpha, which formed
      heterodimers with retinoid X receptor-alpha (RXRalpha), were activated by
      PPARalpha ligands to form ligands-PPARalpha-RXRalpha complexes. Then the
      complexes were transferred into a microplate and captured via monoclonal anti
      PPARalpha antibody. The PPARalpha responsive elements (PPRE) modified-gold
      nanoparticle probes were captured by the ligand-PPARalpha-RXRalpha complexes
      immobilized on the microplate, and then could be quantified through measuring the
      optical density after silver enhancement. The results showed that PFOS was
      quantified with a linear range from 100 pM to 1 MUM and the detection limit was
      10 pM. In addition to PFOS, PFOA and MEHP were also quantified within a proper
      range through the proposed bioassay. This bioassay was compared with that of
      liquid chromatography tandem-mass spectrometry (LC-MS) for water spiked samples
      with a significant correlation (r = 0.9893). This study provides a high
      throughput detection method for PPARalpha ligands in microplate with high
      sensitivity and wide linear range. It may serve as an assistant of LC-MS for
      prescreening of PPARalpha ligands like PFOS.

PMID- 21726939
TI  - Clinically important difference thresholds of the visual analog scale: a
      conceptual model for identifying meaningful intraindividual changes for pain
      intensity.
AB  - The aim of this study was to estimate a range of clinically important difference
      (CID) values of the visual analog scale for pain intensity (VAS-PI), and to
      assess the effect of patient baseline characteristics on VAS change scores. Data
      from a prospective cohort study with 678 patients with subacute and chronic
      temporomandibular disorder pain were analyzed. Patients were divided into 9
      cohorts on the basis of the baseline VAS score and the duration of pain. The CID
      was estimated over a 12-week period, and 2 different methods were used: (1) mean
      change scores, and (2) optimal cutoff point in receiver operator characteristic
      curves. The patient's global impression of change was used as an external
      criterion. The general linear model univariate analysis was applied to assess the
      effect of baseline pain level and duration of pain on the raw VAS change scores,
      while adjusting for age and sex. The CID mean change ranged from 20.9 to 57.5 mm
      (64.1-76.3%), and the CID optimal cutoff point from 11.5 to 28.5 mm (29.9-47.7%).
      For the VAS change scores, the main effect of the variable baseline pain level
      was significant (F=107.09, P<.001). However, there was no significant baseline
      pain level by duration of pain interaction effect (F=1.13, P=.340). On the basis
      of the results, we advocate the choice of a single CID value according to the
      context of the patient's baseline level of pain.

PMID- 21726940
TI  - Haemosporidian infection in captive masked bobwhite quail (Colinus virginianus
      ridgwayi), an endangered subspecies of the northern bobwhite quail.
AB  - The avian haemosporidian parasites (phylum Apicomplexa) are taxonomically diverse
      and cosmopolitan in distribution; infecting most bird families. Sources of
      concern are reports of clinical haemosporidian infections in birds kept as part
      of zoo and aviary collections. Recently, severe and acute mortality episodes have
      been reported in masked bobwhite quail (Colinus virginianus ridgwayi), an
      endangered subspecies from the American Southwest. Two hundred and five eggs of
      the captive flock held in Arivaca, Arizona, were hatched at a zoo in the American
      Southwest. Thirty-four sub-adult or adult animals had lesions associated with
      tissue phases of haemoparasites, especially vasculitis, ventricular leiomyositis
      and ulcerative pododermatitis. Molecular techniques applied to blood collected
      from the zoo's last twelve remaining animals resulted in the detection of a
      Plasmodium juxtanucleare-like and Haemoproteus sp. parasites. A Raven (Corvus
      corax), in a contiguous exhibit, was positive for the same P. juxtanucleare-like
      parasite, but remained asymptomatic for three years following detection. These
      findings indicate that other birds in the exhibit within the zoo premises could
      act as reservoirs. We conclude that haemosporidian infections could be a factor
      in the demise of the captive masked bobwhite quails housed at the zoo. We suggest
      that active surveillance for haemoporidian parasites should be incorporated as a
      precaution to ex situ conservation efforts of susceptible endangered species.

PMID- 21726941
TI  - Influence of protein supplementation during late pregnancy and lactation on the
      resistance of Santa Ines and Ile de France ewes to Haemonchus contortus.
AB  - This experiment aimed to evaluate the effect of periparturient metabolizable
      protein (MP) nutrition on resistance to Haemonchus contortus in single rearing
      Ile de France and Santa Ines ewes. The restriction-fed iso-energetic diet was
      calculated to provide either 0.8 (low MP diet) or 1.3 (high MP diet) times MP,
      from three weeks before parturition until eight weeks into lactation. The ewes
      were experimentally infected with 1000 H. contortus infective larvae (L3) three
      times a week (Mondays, Wednesdays and Fridays), starting five weeks before the
      predicted date for parturition until a total of 15,000 L3 had been administered.
      While both breeds showed elevated fecal egg counts (FEC), these values were
      significantly lower for Santa Ines ewes than Ile de France ewes, but were
      independent of level of MP feeding. The latter also did not affect lamb weight
      gain and ewe body weight variation in each breed. Packed cell volume and total
      plasma protein for Santa Ines in all periods were significantly higher than those
      for Ile de France ewes (P<0.01) but were not affected by nutrition. In contrast,
      levels of serum IgG and IgA antibodies against somatic H. contortus infective
      larvae and adult antigens were similar between breeds but higher in animals that
      received high MP diets (P<0.05). The reduced body score of ewes at the beginning
      of the experiment probably influenced their high susceptibility to incoming
      larvae. Since, unexpectedly, MP scarcity was not achieved in this experiment, our
      data support the view that Santa Ines ewes are more resistant to H. contortus
      than Ile de France ewes.

PMID- 21726942
TI  - Condensed tannins act against cattle nematodes.
AB  - The use of natural plant anthelmintics was suggested as a possible alternative
      control of gastrointestinal nematodes (GIN) in ruminants. Direct anthelmintic
      effects of tannin-containing plants have already been shown in sheep and goat
      GIN. These anthelmintic properties are mainly associated with condensed tannins.
      In the present study, we evaluated possible in vitro effects of three tannin
      containing plants against bovine GIN. Effects of Onobrychis viciifolia, Lotus
      pedunculatus and Lotus corniculatus condensed tannin (CT) extracts on Cooperia
      oncophora and Ostertagia ostertagi were determined by a larval feeding inhibition
      assay (LFIA) and a larval exsheathment assay (LEA). In the LFIA, all three plant
      extracts significantly inhibited larval feeding behaviour of both C. oncophora
      and O. ostertagi first stage larvae in a dose-dependent manner. The L.
      pedunculatus extract, based on EC(50) (effective concentration for 50%
      inhibition), was the most effective against both nematodes, followed by O.
      viciifolia and L. corniculatus. The effect of CT extracts upon larval feeding
      behaviour correlates with CT content and procyanidin/prodelphidin ratio. Larval
      exsheathment of C. oncophora and O. ostertagi L3 larvae (third stage larvae) was
      also affected by CT extracts from all three plants. In both in vitro assays,
      extracts with added polyvinylpolypyrrolidone, an inhibitor of tannins, generated
      almost the same values as the negative control; this confirms the role of CT in
      the anthelmintic effect of these plant extracts. Our results, therefore,
      indicated that tannin-containing plants could act against cattle nematodes.

PMID- 21726944
TI  - In vitro destruction of Eimeria oocysts by essential oils.
AB  - This study aims to assess the ability of essential oils (EOs) to destroy Eimeria
      oocyst in vitro using microscopic counting and 273 nm absorbing material release.
      A screening for the ability of ten EOs to destroy Eimeria oocyst was carried out
      in liquid medium. Out of these ten, artemisia, tea tree, thyme and clove EOs were
      identified as being the most effective. The treatment of Eimeria oocyst with
      these EOs leads to their lysis as shown by the release of substances absorbing at
      273 nm. These results were obtained after approximately three hours contact. Four
      EOs were proven to destroy Eimeria oocysts in a few hours at low concentration.
      This destructive effect is a consequence of their lysis. This work is a
      preliminary contribution aiming to develop a new generation of natural efficient
      agents for destroying Eimeria oocyst to fight coccidiosis in broiler chicken.

PMID- 21726946
TI  - A web-based educational module increases burn prevention knowledge over time.
AB  - Unfortunately, burn prevention knowledge is low among nurses. Establishing
      efficient ways in which to increase burn prevention knowledge in nurses is
      warranted. The current multi-center study evaluated whether a web-based
      educational module was successful at increasing burn prevention immediately and
      whether the knowledge was retained over time. A valid, reliable burn prevention
      knowledge exam was administered to nurse at three time points (prior to receiving
      the educational module, immediately following receiving the educational module,
      and at least a minimum of two weeks after receiving the educational module).
      Generalized linear mixed effects modeling methods were used to evaluate whether
      scores on the burn prevention knowledge exam increased over time, while adjusting
      for traditional covariates (e.g., specialty area, years as a nurse, and years in
      current work area). Mean scores on the burn prevention knowledge exam increased
      over time (p=0.003); establishing that the educational module significantly
      improves scores over time. Mean score prior to receiving the educational module
      was 82.3%; the mean score was 83.8% immediately following receiving the
      educational module, and 86.1% two weeks after receiving the educational module.
      The educational module developed by the authors (www.burnpreventionstudy.org) is
      an efficient way in which to increase burn prevention knowledge and is available
      at their convenience. This education module could be used as a training module
      with nurses involved in burn prevention outreach, and with nurse practitioners,
      physicians, and emergency responders involved in primary care across the life
      span.

PMID- 21726947
TI  - Epidemiology of children admitted to the Dutch burn centres. Changes in referral
      influence admittance rates in burn centres.
AB  - BACKGROUND: In the Beverwijk Burn Centre a remarkable rise has been noted in the
      number of paediatric admissions since 2000. To investigate if this is a national
      trend and, if so, what may have caused it, a retrospective epidemiological study
      has been undertaken. MATERIALS AND METHODS: The databases of the three Dutch burn
      centres were combined. Data on the population at risk for admission in a burn
      centre and data on burns related hospital admissions were added. Two age groups,
      0-4 years and 5-17 years and two time periods, 1995-1999 and 2000-2007, were
      compared. RESULTS: The mean number of paediatric admissions in the Dutch burn
      centres per year increased by 44.0% and 44.3% for the younger children (0-4
      years) and the older children (5-17 years), respectively, whereas the number of
      paediatric burn admissions in other hospitals in the Netherlands decreased. The
      percentage of children that was referred from other hospitals increased in both
      age groups, and for the younger children this was significant. CONCLUSION: There
      has been a shift in paediatric burn care towards a greater volume of admissions
      in specialized burn care of especially young children with less severe burns. A
      possible explanation for the increased number of referred children may be the
      introduction of the EMSB course in 1998, since EMSB guidelines dictate stricter
      and generally accepted referral criteria.

PMID- 21726948
TI  - Self-inflicted burns in the Irish National Burns Unit.
AB  - We carried out a review of self-inflicted burns presenting to the National Burns
      Unit in the Republic of Ireland. 87 self-inflicted burns were identified over a
      12-year period accounting for 4.2% of total Burns Unit admissions. Patient
      demographics were identified. The majority of patients had a history of mental
      illness and deliberate self harm. We also examined the motivation behind the self
      immolation, the total body surface area involved and the mortality rates.

PMID- 21726949
TI  - Sustainable effect of skin stretching for burn scar excision: long-term results
      of a multicenter randomized controlled trial.
AB  - PURPOSE: Primary wound closure of large defects after burn scar excision may be
      facilitated by intraoperative stretching of the adjacent skin. In a randomized
      controlled trial (RCT), the effect of skin stretching for wound closure after
      scar excision (SS) was compared to scar excision without additional techniques
      (SE). Short-term results already showed that in the SS group larger scars could
      be excised in a one-step procedure. In this paper, the long-term scar outcome
      using reliable and valid measurement tools was evaluated. BASIC PROCEDURES: The
      percentage of total remaining scar area (i.e. remaining scar compared to
      preoperative scar), the percentage of linear scarring (i.e. surface area of
      linear scar compared to excised scar) and scar hypertrophy was measured at 3 and
      12 months postoperatively. MAIN FINDINGS: At 12 months postoperatively, the
      percentage of total remaining scar area was significantly lower in the SS group
      (26%) compared to the SE group (43%). The percentage of linear scarring (SS: 21%,
      SE: 25%) and the incidence of hypertrophy (SS: 29%, SE: 40%) were not
      significantly different between the treatment groups. CONCLUSIONS: This RCT
      demonstrates the long-term beneficial and sustainable effect skin stretching for
      wound closure after scar excision without leading to wider linear scars or more
      scar hypertrophy.

PMID- 21726950
TI  - Return to German professional soccer league (Bundesliga) 6 months after severe
      burn: a case report.

PMID- 21726951
TI  - Molten copper inhalation.

PMID- 21726952
TI  - Reimbursement of burns by DRG in four European countries: an analysis.
AB  - PURPOSE: To analyze the German, Austrian, Italian and Spanish Diagnosis-Related
      Group (DRG)-systems regarding burns. METHODS: We analyzed 78 cases of inpatients
      with burns which were processed by national DRG-groupers. DRGs were linked to
      thresholds concerning length of stay as well as reimbursement tables of the
      respective countries. MAIN FINDINGS: Fifty-one % of cases showed higher
      reimbursement in Germany compared to Austria, 55% compared to Italy and 67% as
      against Spain. Total proceeds are highest in Austria with 1,577,000 ?, followed
      by Italy with 1,569,000 ?, Germany with 1,502,000 ? and Spain with 902,596 ?. No
      correlation was found between macroeconomic key figures and our data.
      CONCLUSIONS: International comparison of reimbursement of burns by DRG could be a
      useful instrument for benchmarking while not depending solely on political
      decisions or country-specific cost data. For better comparability, hospital
      indices based on healthcare baskets should be discussed.

PMID- 21726953
TI  - Epidemiological study of burns in Komfo Anokye Teaching Hospital, 2006-2009.
AB  - AIM: To identify and describe the patterns of burns reported at the Komfo Anokye
      Teaching Hospital (KATH) from 2006 to 2009 and their outcomes on the various age
      groups and genders. METHODS: Patients' records from admission and discharge books
      of the Burns Intensive Care Unit, Polyclinic Casualty Consulting Rooms and from
      the Statistical Department of KATH were reviewed to obtain the necessary data for
      this retrospective study. Data entry and analysis were done by using SPSS version
      17.0. RESULTS: A total of 731 patients' records were reviewed, with male to
      female ratio of 1.2:1. The mean age was 15.83 years; range was 0-79 years.
      Children less than 10 years were the most frequently admitted group (53.5%). Most
      of the burns occurred in domestic settings (88.5%), whiles, majority of the burns
      were accidental (98.8%). Scalds (57.4%) were the most frequent cause of burns
      followed by open flame (38.2%). The mortality rate was 13.1% for the period under
      review. Majority (71.4%) of the patients spent less than 10 days on admission.
      The mean total body surface area (TBSA) was 24.79%, and there was significant
      correlation between TBSA, age group, outcome and duration of hospital admission.
      CONCLUSION: Children less than 10 years were the most vulnerable victims to
      burns; males dominated the number of victims. The commonest aetiological factor
      was scalds, with most of them related to inattention from parents. More dedicated
      burn surgeons and properly trained nurses are needed at KATH. Ambulance and pre
      hospital services should be increased with adequate number of paramedics.
      Coordination between district hospitals and tertiary burn centres should also be
      established, for the proper transfer of burn cases to the tertiary burn centres,
      especially KATH.

PMID- 21726956
TI  - A response to: "Air ambulance transfer of adult patients to a UK regional burns
      centre: who needs to fly".

PMID- 21726958
TI  - An audit of patients' experiences and opinions concerning mirrors in a UK burns
      service.
AB  - Patients' experiences of and opinions concerning the presence of mirrors in burns
      services are unknown. The prevalence of mirrors and associated nursing practice
      in UK burns services is also unclear. Recently discharged burns patients (n=60)
      completed a questionnaire and representatives from all 18 adult burns inpatient
      services in the UK were surveyed. Results suggested that 90% of patients with
      facial burns viewed their injuries in a mirror before discharge compared to 15%
      of patients with burns elsewhere. Thirty-six percent of patients reported they
      were informed that they could request a mirror if desired and 30% were asked
      whether they would like a mirror. Only 22% of patients reported that they would
      not have liked mirrors in their rooms/ward area and 14% reported that this would
      have distressed them. It was patients who most often decided to view their
      injuries for the first time and nurses were most commonly present. Mirrors were
      present in most UK burns services but none had protocols to guide staff in
      helping patients view their injuries. In conclusion, concealable mirrors should
      be present in burns services but patients should be psychologically prepared
      about their presence. Protocols should be developed to provide optimal burn care.

PMID- 21726959
TI  - Activity and resistance of trastuzumab according to different clinical settings.
AB  - Trastuzumab, a humanized monoclonal antibody directed against HER2, has shown
      efficacy in breast cancers; however many patients do not respond to this reagent.
      Here, we discuss the potential mechanisms of trastuzumab efficacy and resistance
      in different clinical settings as a step toward optimizing the appropriate
      application of this antibody. The three major antitumor mechanisms of
      trastuzumab, i.e., inhibition of proliferation, antibody-dependent cell
      cytotoxicity (ADCC) and inhibition of DNA repair, appear to be differentially
      operative in different clinical settings. ADCC appears to be the prevalent
      mechanism in trastuzumab neoadjuvant monotherapy, whereas in neoadjuvant,
      adjuvant or metastatic settings in which trastuzumab is combined with
      chemotherapy, the relative role of ADCC is probably small, considering the
      compromising effects of chemotherapy on the immune cells that mediate this
      mechanism. In neoadjuvant and adjuvant settings involving concomitant use of
      trastuzumab and chemotherapy, the primary mechanism at play is presumably
      inhibition of DNA repair by the antibody, while in sequential protocols, the
      antibody acts mostly by exerting cytostatic activity through inhibition of HER2
      mediated tumor cell proliferation. According to the ability of the antibody to
      induce cytotoxic or cytostatic antitumor effects depending on the clinical
      setting, different criteria, i.e., RECIST for cytotoxic effect, OS, and DFS for
      cytostatic, must be considered in accurately estimating antibody efficacy.
      Moreover, since trastuzumab resistance likely depends directly on the mechanisms
      responsible for its antitumor activity, resistance mechanisms must also be
      considered with respect to the different clinical settings.

PMID- 21726960
TI  - Locoregional radiological treatment for hepatocellular carcinoma; Which, when and
      how?
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest cancers
      worldwide. Liver transplantation, surgical resection or local ablation offer the
      best survival advantages but most patients either present when the tumor is in an
      advanced stage or the degree of underlying liver disease precludes these options.
      Several therapies have been proposed for these patients with proven survival
      benefits. These therapies comprise the locoregional treatment for HCC, and
      include percutaneous ethanol injection (PEI), radiofrequency ablation (RFA),
      transarterial chemoembolization (TACE), transarterial radioembolization (TARE),
      and drug-eluting bead (DEB). PEI and RFA are considered curative treatments for
      early stage HCC; whereas TACE is a standard of care for intermediate stages.
      Additionally, evaluation of response to locoregional treatment in HCC is
      important, as objective response may become a surrogate marker for improved
      survival. Currently, there are several criteria for response assessment,
      including the World Health Organization (WHO), the Response Evaluation Criteria
      in Solid Tumors (RECIST), the European Association for the Study of the Liver
      Criteria (EASL), and the modified RECIST (mRECIST); however, there has been poor
      correlation between the clinical benefit provided by locoregional interventional
      therapies and conventional methods of response assessment. The aim of our study
      was to review and analyze the current evidence for radiological interventions in
      HCC, and to propose evidence based recommendations to improve the management of
      these patients.

PMID- 21726961
TI  - Normal-tension glaucoma and Alzheimer's disease: retinal vessel signs as a
      possible common underlying risk factor.

PMID- 21726962
TI  - The "somatic-spread" hypothesis for sporadic neurodegenerative diseases.
AB  - The major neurodegenerative diseases (Alzheimer's disease, Parkinson's disease
      and amyotrophic lateral sclerosis) share in common a mostly sporadic occurrence,
      a focal onset of pathology, and spread from the initial site of injury to
      adjacent regions of the nervous system. The sporadic nature and focal onset of
      these diseases can be explained either by somatic mutations (arising in either of
      two models of cell lineage) or environmental agents, both of which affect a small
      number of neurons. The genetic or environmental agent then changes the
      conformation of a vital protein in these neurons. Spread of the diseases occurs
      by the misfolded proteins being transferred to adjacent neurons. Clinical and
      pathological details of one neurodegenerative disorder, amyotrophic lateral
      sclerosis, are presented to show how the pathogenesis of a typical
      neurodegenerative disease can be explained by this "somatic-spread" hypothesis.
      Ultrasensitive techniques will be needed to detect the initiating genetic or
      environmental differences that are predicted to be present in only a few cells.

PMID- 21726963
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9
      (MMP-9) prognostic value in stage I colorectal carcinoma.
AB  - The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been
      suggested to behave like a negative prognostic marker in stage I colorectal
      carcinoma. In the aim of clarifying whether its association with adverse outcome
      may descend from NGAL's ability to regulate matrix metallo-proteinase-9 (MMP-9),
      we analyzed the correlation, prognostic value, and association with neo
      angiogenesis of NGAL and MMP-9 immunohistochemical expression in a series of
      stage I colorectal carcinomas. A variable NGAL immunoexpression was demonstrated
      in 17 of the 48 analyzed cases with a significantly higher frequency of positive
      cases among patients showing disease progression. NGAL expression was also
      positively correlated with VEGF expression detected in the same cases. MMP-9
      immunostaining was present in the cytoplasm of the neoplastic cells in 30 cases;
      no significant correlations were evidenced with NGAL expression, as well as with
      the various clinico-pathological parameters or with progression of the colorectal
      carcinomas. By contrast, NGAL expression was confirmed as a significant
      independent negative prognostic marker related to a shorter disease-free survival
      in stage I colorectal carcinoma. Our preliminary results suggest that the
      association of NGAL with poor outcome might be independent from MMP-9 regulation,
      thus highlighting its prognostic value in this neoplasia. If our findings are
      confirmed in further analyses, NGAL assessment might be used in order to select
      those patients with a higher progression risk and to submit them to adjuvant
      therapies useful to prevent adverse outcome.

PMID- 21726964
TI  - Smoking-related prospective memory deficits in a real-world task.
AB  - BACKGROUND: Smokers, previous smokers and a never smoked group were compared on
      self-reported and real world prospective memory (PM - the cognitive ability of
      remembering to carry out particular actions at some future point in time).
      METHODS: Twenty-seven current smokers, 24 people who had never smoked and 18
      previous smokers were compared using an existing groups design. Scores on the
      long and short term PM subscales of the Prospective and Retrospective Memory
      Questionnaire (PRMQ) and scores on a Real World Prospective Memory Task (RWPMT)
      constituted the dependent measures. Smoking and other drug use were assessed by a
      Recreational Drug Use Questionnaire. The Hospital Anxiety and Depression Scale
      gauged levels of anxiety and depression. The National Adult Reading Test measured
      IQ, and retrospective memory was measured using the PRMQ. Gender, age, anxiety
      and depression, IQ, alcohol use and the retrospective memory scores, were
      measured as covariates and controlled for in the analysis. RESULTS: A series of
      univariate ANCOVAs were applied to the main PM data across the three groups,
      controlling for variations in age, gender, mood, IQ, alcohol use and
      retrospective memory scores. These revealed no significant between-group
      differences on self-reported PM; however smokers recalled significantly fewer
      action-location combinations than the never smoked and previous smoker groups on
      the objective RWPMT. CONCLUSIONS: Existing smokers showed reduced performance on
      RWPMT when compared to the never smoked group and previous smokers. Real-world PM
      impairments should be added to a growing list of neuropsychological sequelae
      associated with persistent smoking.

PMID- 21726965
TI  - Susceptibility of rapidly growing mycobacteria and Nocardia isolates from cats
      and dogs to pradofloxacin.
AB  - Rapidly growing mycobacteria (RGM) and Nocardiae can cause severe or refractory
      infections in cats and dogs. Prolonged antibacterial therapy is required to cure
      these infections. As fluoroquinolones have been used in combination therapy for
      treating RGM infections, isolates from the Mycobacterium smegmatis cluster
      (n=64), Mycobacterium fortuitum cluster (n=17), and M. mageritense cluster (n=2),
      collected from feline and canine patients, underwent susceptibility testing to
      pradofloxacin. The MIC(50), MIC(90) and tentative epidemiological cut-off (ECOFF)
      values as determined by microbroth dilution susceptibility testing that inhibited
      growth of the M. smegmatis and M. fortuitum clusters were 0.063, 0.125 and <=
      0.25; and 0.125, 0.250 and <= 1.0 MUg/mL, respectively. E-Test results showed
      similar trends but MICs were lower than those for microbroth dilution. In
      summary, pradofloxacin demonstrated effective in vitro activity against RGM
      isolates. Additionally, veterinary isolates of Nocardia nova (n=18), Nocardia
      farcinica (n=3) and Nocardia cyriacigeorgica (n=1) underwent microbroth dilution
      testing to ciprofloxacin, enrofloxacin and pradofloxacin. The MIC(50) and MIC(90)
      of pradofloxacin, ciprofloxacin and enrofloxacin that inhibited growth of
      Nocardia nova isolates were 2 (4), 8 (16), 16 (32) MUg/mL, respectively. The
      tentative ECOFF values for pradofloxacin and ciprofloxacin were 32 MUg/mL and for
      enrofloxacin 64 MUg/mL. The MIC or MIC range for the three N. farcinica isolates
      of pradofloxacin, ciprofloxacin and enrofloxacin were 0.25-0.5, 2 and 2 MUg/mL
      and for the single N. cyriacigeorgica isolate were 1, 4 and 4 MUg/mL,
      respectively. On the basis on these results, fluoroquinolones appear to have
      limited therapeutic potential for most Nocardia infections.

PMID- 21726966
TI  - Development of a bead-based multiplex PCR assay for the simultaneous detection of
      multiple Mycoplasma species.
AB  - We describe the development and analytical validation of a 7-plex polymerase
      chain reaction assay coupled to a bead-based liquid suspension array for
      detection of multiple ruminant Mycoplasma spp. The assay employs a combination of
      newly designed and previously validated primer-probe sets that target genetic
      loci specific for Mycoplasma bovis, Mycoplasma mycoides cluster, Mycoplasma
      mycoides subsp. mycoides SC (MmmSC) and Mycoplasma capricolum subspecies
      capripneumoniae (Mccp). Analytical sensitivity for the targeted Mycoplasma
      species ranged from 10 fg to 1 pg of purified gDNA extracted from broth cultures
      (approximately 8-800 MmmSC genome equivalents). In silico comparison of primers
      and probes, and analytical assessment with a range of near-neighbor Mycoplasma
      species and multiple bacterial respiratory pathogens demonstrated 100% analytical
      specificity of the assay. To assess assay performance and diagnostic specificity,
      192 bovine respiratory samples were analyzed by incorporating a high throughput
      DNA extraction platform. The assay correctly classified all samples as negative
      for MmmSC or Mccp. All 33 field samples confirmed as positive for M. bovis by
      sequencing the uvrC gene were positive in the assay. The results from this study
      indicate that the bead-based liquid suspension array will provide a reliable,
      analytically sensitive and specific platform to simultaneously interrogate
      ruminant respiratory samples for multiple Mycoplasma species, including M.
      mycoides cluster organisms that are exotic to the United States. Sequential
      addition of primer-probe sets to the assay did not significantly impact
      analytical sensitivity of individual primer-probe combinations, suggesting that
      expanding the assay to include more Mycoplasma species will not compromise
      overall performance.

PMID- 21726967
TI  - The effect of zinc chloride, humidity and the substrate on the reaction of 1,2
      indanedione-zinc with amino acids in latent fingermark secretions.
AB  - Anecdotal evidence from forensic practitioners and studies conducted under
      controlled conditions have indicated that the reaction between 1,2-indanedione
      and the amino acids present in latent fingermark deposits is highly susceptible
      to ambient humidity. The addition of catalytic amounts of zinc chloride to the
      1,2-indanedione working solution--usually in the order of 1:25 to 1:4 molar ratio
      (indanedione:zinc)--significantly improves the colour and luminescence of
      fingermarks treated under dry conditions but appears to have a negligible effect
      on fingermarks treated in humid environments. The results presented in this paper
      confirmed that zinc(II) ions added to the 1,2-indanedione working solution act as
      a Lewis acid catalyst, stabilising a key intermediate during a rate-limiting
      hydrolysis step. Furthermore, studying the reaction using a chromatography-grade
      cellulose substrate method previously reported confirmed that cellulose
      substrates play a major role in facilitating the indanedione-amino acid reaction
      by acting as a surface catalyst in the early stages of the reaction and by
      directing the formation of the desired luminescent product (Joullie's Pink).

PMID- 21726968
TI  - A complete passive blind image copy-move forensics scheme based on compound
      statistics features.
AB  - Since most sensor pattern noise based image copy-move forensics methods require a
      known reference sensor pattern noise, it generally results in non-blinded passive
      forensics, which significantly confines the application circumstances. In view of
      this, a novel passive-blind image copy-move forensics scheme is proposed in this
      paper. Firstly, a color image is transformed into a grayscale one, and wavelet
      transform based de-noising filter is used to extract the sensor pattern noise,
      then the variance of the pattern noise, the signal noise ratio between the de
      noised image and the pattern noise, the information entropy and the average
      energy gradient of the original grayscale image are chosen as features, non
      overlapping sliding window operations are done to the images to divide them into
      different sub-blocks. Finally, the tampered areas are detected by analyzing the
      correlation of the features between the sub-blocks and the whole image.
      Experimental results and analysis show that the proposed scheme is completely
      passive-blind, has a good detection rate, and is robust against JPEG compression,
      noise, rotation, scaling and blurring.

PMID- 21726969
TI  - Severe muscle damage following viral infection in patients with Fukuyama
      congenital muscular dystrophy.
AB  - Fukuyama congenital muscular dystrophy (FCMD), which is characterized by cortical
      migration defect and eye abnormalities, is the most common subtype of CMD in
      Japan. Fukutin (FKTN), the responsible gene for FCMD, encodes a protein involved
      in the glycosylation of alpha-dystroglycan. We have experienced some patients
      with FCMD who showed sudden exacerbation of muscle weakness with marked elevation
      of serum creatine kinase (CK) and urinary myoglobin levels a few days after a
      febrile episode of viral infection, occasionally leading to death. To describe
      this peculiar phenomenon, we focused on 12 patients who developed a sudden
      exacerbation of muscle weakness among 96 genetically defined FCMD patients and
      hospitalized because of a febrile illness at Tokyo Women's Medical University
      between 1997 and 2008. All the 12 patients were homozygous for a 3-kb insertion
      mutation of FKTN. The patients developed exacerbation of muscle weakness ranging
      from paralysis to loss of head control. The onset was concentrated in summer, and
      coxsackieviruses and enteroviruses were most often detected, especially in
      infantile patients. Eight of the 12 patients were treated with corticosteroids
      and recovered within 2 weeks. Four patients were treated without steroid, and
      needed 18.5 days on mean for improvement. None developed renal failure. The
      reason for muscle damage induced by viral infection remains unknown; however,
      physicians should consider its risk, sometimes leading to death, and draw it to
      parents' attention, especially in the defervescent stage.

PMID- 21726970
TI  - Higher precontrast CT density of the carotid plaque in the symptomatic patients.
AB  - PURPOSE: The purpose of this study was to determine if there is a significant
      difference in the CT Hounsfield Unit (CTHU) of the carotid atherosclerotic plaque
      (CAP) on CTpre and CTartery depending on the presence of symptomatology. METHODS:
      Quantitative analysis of the CTHUs for the CAP was performed in 43 arteries (11
      symptomatic arteries, 32 asymptomatic arteries). The CTHUs were measured using
      the manual ROI method for each CAP. Group differences in the CTHU of the CAP
      depending on the symptomatology were evaluated by using the independent t-test.
      RESULTS: The CTHUs of CAP on CTpre were significantly higher in the symptomatic
      arteries than those of the asymptomatic arteries (P=0.036). The CTHUs of CAP on
      CTartery were not significantly different regardless of symptomatology.
      CONCLUSION: The CTHUs of the CAP on CT(pre) may be used as one of the biomarkers
      to distinguish the vulnerable CAP.

PMID- 21726971
TI  - Radiological aspects of prenatal-onset cortical hyperostosis [Caffey Dysplasia].
AB  - OBJECTIVE: Cortical hyperostosis is a bone disease that may, at times, occur with
      a prenatal onset. This study seeks to present the characteristic patterns of
      prenatal-onset cortical hyperostosis (PCH) with regard to the radiographic
      features, and tries to ascertain whether PCH is a separate entity from infantile
      cortical hyperostosis (ICH), known as classic Caffey Disease. MATERIALS AND
      METHODS: This retrospective study identified cases with PCH based upon abnormal
      radiographic and chondro-osseous morphological and clinical findings, as
      available, from the International Skeletal Dysplasia Registry between 1987 and
      2009. Outcomes and clinical information were also identified from medical
      records. RESULTS: Based upon radiographic results, we found 20 individuals with
      PCH, of whom 10 neonatally survived, and 10 died. Hyperostosis of the mandible
      was found in 18/20, and of the skull base in 16/20 cases. Hyperostosis of the
      ribs was found in 17/20 cases, of the scapulae in 14/20, and of the clavicles in
      4/20. Hyperostosis of the ileum was found in 11/20 cases, and of the long bones
      in all 20/20 cases, of which three cases had fibula sparing. No hyperostosis of
      the hands, feet, and spine was found. CONCLUSIONS: Our results suggest that,
      based upon clinical features and radiographic expression, ICH and PCH represent
      two separate entities, and that ICH should continue to be referred to as Caffey
      Disease and that PCH should be called Caffey Dysplasia. The findings of
      symmetrical hyperostosis of the mandible, ribs, scapulae, ilea, and long bones in
      any combination should suggest the diagnosis of PCH.

PMID- 21726972
TI  - Nonenhanced ECG-gated time-resolved 4D steady-state free precession (SSFP) MR
      angiography (MRA) of cerebral arteries: comparison at 1.5T and 3T.
AB  - PURPOSE: To compare image quality of nonenhanced time-resolved 4D steady-state
      free precession MR angiography (4D SSFP MRA) of cerebral arteries at 1.5T and 3T.
      MATERIALS AND METHODS: 12 healthy subjects (mean age 29.4+/-6.9 years) were
      studied at both 1.5T and 3T. Two different positions of the acquisition slab were
      evaluated; in one acquisition the imaging slab included the carotid siphon
      ("S(low)"), in the other acquisition the imaging slab was placed superior to the
      carotid siphon ("S(high)"). Subjective image quality of cerebral arteries was
      assessed independently by two readers on a 4-point scale. Relative Signal-to
      Noise-Ratio (SNR) was determined for the M1 segment of the middle cerebral
      artery. RESULTS: Subjective image quality of the anterior cerebral artery
      (segments A1, A2) was significantly higher at 1.5T as compared to 3T, while 3T
      provided significantly higher image quality for segment P3 of the posterior
      cerebral artery. For the middle cerebral artery (segments M1-M3), image quality
      was significantly higher at 1.5T than at 3T when the carotid siphon was included
      in the acquisition slab ("S(low)"), while no significant difference was found
      between 1.5T and 3T with "S(high)". Relative SNR was significantly higher at 1.5T
      (23.1+/-5.1) as compared to 3T (12.1+/-7.8) for "S(low)" and significantly higher
      at 3T (29.8+/-5.9) than at 1.5T (24.2+/-3.6) for "S(high)". CONCLUSION: Our
      results indicate that 4D SSFP MRA should preferably be performed at 1.5T with
      inclusion of the carotid siphon in the acquisition slab, which might be required
      for the assessment of intracranial collateral flow.

PMID- 21726973
TI  - In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction
      injury following mesenchymal stem cell transplantation.
AB  - OBJECTIVE: To assess the continuous process of nerve regeneration in acute
      peripheral nerve traction injury treated with mesenchymal stem cells (MSCs)
      transplantation using MRI. MATERIALS AND METHODS: 1 week after acute nerve
      traction injury was established in the sciatic nerve of 48 New Zealand white
      rabbits, 5*10(5) MSCs and vehicle alone were grafted to the acutely distracted
      sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the
      injured nerves were performed with a 1.5-T scanner and functional recovery was
      recorded over a 10-week follow-up period, with histological assessments performed
      at regular intervals. RESULTS: Compared with vehicle control, nerves grafted with
      MSCs had better functional recovery and showed improved nerve regeneration, with
      a sustained increase of T1 and T2 values during the phase of regeneration.
      CONCLUSION: MRI could be used to monitor the enhanced nerve regeneration in acute
      peripheral nerve traction injury treated with MSC transplantation, reflected by a
      prolonged increase in T1 and T2 values of the injured nerves.

PMID- 21726974
TI  - Identification of a new sildenafil analogue in a health supplement.
AB  - A sildenafil analogue was detected and isolated from a health supplement claimed
      for human use. The structure of this new analogue was elucidated using LC-UV, LC
      Orbitrap-MS, IR spectroscopy, 1D and 2D NMR. It was characterized as dithio
      desmethylcarbodenafil containing 2 thiocarbonyl groups instead of 2 carbonyl
      groups, and 4-methyl substitution, on the piperazine ring, rather than 4-ethyl
      substitution, when compared to sildenafil.

PMID- 21726975
TI  - Validation of the new AJCC TNM staging system for gastric cancer in a large
      cohort of patients (n = 2,155): focus on the T category.
AB  - BACKGROUND: The prognostic value of T subclassification in patients with gastric
      carcinoma has been just implemented in the new AJCC TNM staging system, which has
      reclassified T2a and T2b into T2 and T3 tumors, respectively. The aim of the
      present study was to validate the prognostic significance of the new T
      categorization within the frame of the latest TNM staging system. METHODS: We
      retrospectively reviewed the records of 686 T2/T3 patients among 2155 subjects
      who underwent radical resection for gastric carcinoma at six Italian centers from
      1988 through 2006. RESULTS: Upon multivariate analysis, the new T categories,
      extent of lymph node dissection (D) and patient's age were retained by the
      survival model as independent prognostic factors. In particular, the death risk
      for patients with T3 tumors was higher than that of patients with T2 tumors (HR:
      1.42, P = 0.005). Among the 686 patients previously classified as having T2
      tumors, patients with T2 and T3 disease were 270 (39.4%) and 416 (60.6%),
      respectively. After a median follow-up of 55 months, the 5-year overall survival
      rates were 67.3% and 52.3% for patients with T2 and T3 tumors, respectively (P <
      0.001). The survival advantage for the T2 as compared to T3 category was
      maintained even when N0 and N+ patients were separately considered (P = 0.0154
      and P < 0.001, respectively). CONCLUSIONS: Our data confirm the prognostic
      difference between the newly proposed T2 and T3 categories, which should be
      implemented in the routine clinical practice to improve risk stratification of
      patients with gastric cancer.

PMID- 21726976
TI  - The value of post-neoadjuvant therapy PET-CT in the detection of interval
      metastases in esophageal carcinoma.
AB  - BACKGROUND: PET-CT scanning is increasingly applied in the primary work-up of
      esophageal cancer patients. The additional value of a second PET-CT after
      completion of neoadjuvant therapy (NT) prior to surgery is presently unclear.
      Therefore, a consecutive series of esophageal cancer patients underwent PET-CT
      scanning after completion of NT for evaluation of metastatic disease that became
      manifest under NT. METHODS: A consecutive series of patients planned for curative
      esophagectomy who underwent a PET-CT prior to and after NT were included in this
      study. Neoadjuvant therapy consisted of 5FU and cisplatinum combined with 50.4Gy
      radiotherapy. The first PET-CT was performed as part of the diagnostic work-up,
      the second PET-CT was performed after completion of NT and prior to surgery.
      Median interval between NT and second PETCT was 6 weeks. In case of metastatic
      disease on the post-neoadjuvant therapy PET-CT confirmed by a biopsy, patients
      were excluded from surgical resection. RESULTS: Between November 2008 and July
      2010 a total of 50 patients underwent first and second PET-CT scanning. 80% of
      patients was diagnosed with adenocarcinoma, 18% with squamous cell carcinoma.
      Confirmed metastatic disease on the second PET-CT was present in 4/50 patients
      (8%). These patients were excluded from resection. A false-positive diagnosis
      concerning a pulmonary lesion was present in 1 patient (2%); this infiltrate had
      disappeared on follow up imaging. DISCUSSION: This study showed development of
      metastatic disease during NT detected by PET-CT in 8% of esophageal cancer
      patients, suggesting an additional value of a second PET-CT in order to prevent
      unnecessary surgical resections.

PMID- 21726977
TI  - LVQ algorithm with instance weighting for generation of prototype-based rules.
AB  - Crisp and fuzzy-logic rules are used for comprehensible representation of data,
      but rules based on similarity to prototypes are equally useful and much less
      known. Similarity-based methods belong to the most accurate data mining
      approaches. A large group of such methods is based on instance selection and
      optimization, with the Learning Vector Quantization (LVQ) algorithm being a
      prominent example. Accuracy of LVQ depends highly on proper initialization of
      prototypes and the optimization mechanism. This paper introduces prototype
      initialization based on context dependent clustering and modification of the LVQ
      cost function that utilizes additional information about class-dependent
      distribution of training vectors. This approach is illustrated on several
      benchmark datasets, finding simple and accurate models of data in the form of
      prototype-based rules.

PMID- 21726978
TI  - Modeling the role of basal ganglia in saccade generation: is the indirect pathway
      the explorer?
AB  - We model the role played by the Basal Ganglia (BG) in the generation of voluntary
      saccadic eye movements. The BG model explicitly represents key nuclei like the
      striatum (caudate), Substantia Nigra pars reticulata (SNr) and compata (SNc), the
      Subthalamic Nucleus (STN), the two pallidal nuclei and Superior Colliculus. The
      model is cast within the Reinforcement Learning (RL) framework, with the dopamine
      representing the temporal difference error, the striatum serving as the critic,
      and the indirect pathway playing the role of the explorer. Performance of the
      model is evaluated on a set of tasks such as feature and conjunction searches,
      directional selectivity and a successive saccade task. Behavioral phenomena such
      as independence of search time on number of distractors in feature search and
      linear increase in search time with number of distractors in conjunction search
      are observed. It is also seen that saccadic reaction times are longer and search
      efficiency is impaired on diminished BG contribution, which corroborates with
      reported data obtained from Parkinson's Disease (PD) patients.

PMID- 21726979
TI  - Implications of dietary alpha-linolenic acid in bone health.
AB  - Recent evidence implies the benefit of omega-3 polyunsaturated fatty acids in
      bone health. Although eicosapentaenoic acid and docosahexaenoic acid, present in
      fish oil, have been extensively researched, much less is known about the
      influence of alpha-linolenic acid (ALA; present in flaxseeds), a metabolic
      precursor of eicosapentaenoic acid and docosahexaenoic acid, on bone. Our
      objective was to evaluate the published literature and distinguish between the
      individual effects of flaxseed oil and flax lignans on bone to elucidate the
      exact role of ALA in skeletal biology. The search was conducted in several
      databases resulting in 129 articles of which 30 were eligible for inclusion in
      this review. The studies showed that consumption of whole flaxseeds did not lead
      to a marked improvement of osteoporotic bones in humans and animals. However,
      when combined with estrogen therapy, flaxseed supplementation offered an extra
      benefit to bone in animal models. Similar results were found in studies conducted
      with flaxseed oil (predominantly ALA), but the favorable role of flaxseed oil was
      more obvious in various pathologic conditions (kidney disease, obesity with
      insulin resistance), resulting in improved bone properties. In contrast, despite
      a marginal estrogenic effect, the consumption of flax lignans resulted in little
      benefit to bone and the effect was limited to early life of females only in
      animal models. Based on the available studies, it could be concluded that
      supplementation with flaxseeds may contribute to some improvement in osteoporotic
      bone properties but the bone-protective effect may be attributed to ALA, not to
      the lignan fraction of flaxseeds.

PMID- 21726980
TI  - The sleep-deprived brain in normals and patients with juvenile myoclonic
      epilepsy: a perturbational approach to measuring cortical reactivity.
AB  - Simultaneous electroencephalography-transcranial magnetic stimulation (EEG-TMS)
      investigates cortical reactivity to external perturbations. TMS evoked potentials
      (TEPs) have been described in normals during sleep and wake but not after sleep
      deprivation or in pathologically enhanced excitability, i.e., epilepsy. The aim
      of our study was to identify TEPs and their modifications via EEG-TMS co
      registration in healthy controls and patients with juvenile myoclonic epilepsy
      (JME) during wake, sleep deprivation and sleep conditions. Focal TMS was
      administered to the primary motor cortex in 12 healthy controls and 10 patients
      with JME. At least 150 TMS were delivered randomly every 8-15s during wake, sleep
      deprivation and sleep conditions. EEG was simultaneously acquired from 32 scalp
      electrodes. A significant increase in late peak amplitudes (P100 and N190) was
      observed in all subjects during the sleep-deprived condition, with a marked
      anterior increase and overall higher amplitude potentials in the JME patients. We
      demonstrated an overall higher cortical excitability in the JME patients,
      particularly over the anterior cortex after sleep deprivation and rebound sleep.
      This phenomenon could be related to the cortico-thalamic circuit dysfunctions
      believed to cause myoclonic epilepsy and a higher susceptibility of the frontal
      and prefrontal areas to the effects of sleep deprivation.

PMID- 21726981
TI  - Using structural equations to test for a direct effect of some antipsychotics on
      triglyceride levels in drug-naive first-episode psychosis patients.
AB  - Some antipsychotics probably increase the risk of metabolic syndrome.
      Antipsychotics may differentially influence some elements of metabolic syndrome
      (obesity, hyperlipidemia, hyperglycemia or hypertension) through various
      pharmacological mechanisms. In a published study of all first psychotic episodes
      in a Spanish hospital's catchment area population in Cantabria (Spain), patients
      were randomly assigned to receive haloperidol (3-9 mg/day), olanzapine (5
      20mg/day) or risperidone (3-6 mg/day). In this article, a structural-equation
      modeling approach tested the mechanistic hypothesis that olanzapine directly
      (without the mediation of weight gain) increases triglyceride levels, whereas
      risperidone and haloperidol do not have these effects. A structural equation
      model was built using the 110 patients whose assigned antipsychotic was not
      changed during the first 3 months of treatment, and who provided both
      triglyceride and body mass index (BMI) measurements at baseline and at the end of
      the 3rd month of treatment. A second structural equation included 72 patients
      whose antipsychotic was not changed during the first year. After 3 months and
      controlling for confounders, olanzapine patients had triglyceride levels that
      were 29.2mg/dL higher [95% confidence interval, (10.9, 47.5)] than those of
      risperidone patients with comparable baseline triglyceride levels. After 12
      months, they were 63.1mg/dL higher (18.6, 107.6) than those of patients with a
      comparable history of triglyceride values during the first 3 months. Haloperidol
      effects on triglyceride levels and BMI were no different from those of
      risperidone. In conclusion, olanzapine increased triglyceride levels without the
      mediation of weight gain during a one-year study in naive patients.

PMID- 21726982
TI  - L-3-Phosphoserine phosphatase (PSPH) regulates cutaneous squamous cell carcinoma
      proliferation independent of L-serine biosynthesis.
AB  - BACKGROUND: L-3-Phosphoserine phosphatase (PSPH) is a highly conserved and widely
      expressed member of the haloacid dehalogenase superfamily and the rate-limiting
      enzyme in l-serine biosynthesis. We previously found Psph expression to be
      uniquely upregulated in a alpha6beta4 integrin transgenic mouse model that is
      predisposed to epidermal hyperproliferation and squamous cell carcinoma (SCC)
      formation implicating a role for Psph in epidermal homeostasis. OBJECTIVE: We
      examined the status of PSPH in normal skin epidermis and skin tumors along with
      its sub-cellular localization in epidermal keratinocytes and its requirement for
      squamous cell carcinoma (SCC) proliferation. METHODS: First, an
      immunohistochemical study was performed for PSPH in normal skin and skin cancer
      specimens and in cultured keratinocytes. Next, biochemical analyses were
      performed to confirm localization of PSPH and to identify candidate binding
      proteins. Finally, proliferation and apoptosis studies were performed in human
      SCC and normal keratinocytes, respectively, transduced with vectors encoding
      small hairpin RNAs targeting PSPH or overexpressing a phosphatase-deficient PSPH
      mutant. RESULTS: PSPH is expressed throughout the proliferative layer of the
      epidermis and hair follicles in rodent and human skin and is highly induced in
      SCC. In keratinocytes, PSPH is a cytoplasmic protein that primarily localizes to
      endosomes and is present primarily as a homodimer. Knock down of PSPH
      dramatically diminished SCC cell proliferation and cyclin D1 levels in the
      presence of exogenous of l-serine production suggesting a non-canonical role for
      PSPH in epithelial carcinogenesis. CONCLUSIONS: Psph is highly induced in
      proliferative normal keratinocytes and in skin tumors. PSPH appears to be
      critical for the proliferation of SCC cells; however, this phenomenon may not
      involve the phosphoserine metabolic pathway.

PMID- 21726983
TI  - In vitro and in vivo antibacterial activities of garenoxacin against group G
      Streptococcus dysgalactiae subsp. equisimilis.
AB  - In this study, garenoxacin showed potent in vitro activity against clinical
      isolates of group G Streptococcus dysgalactiae subsp. equisimilis [minimum
      inhibitory concentration for 90% of the organisms (MIC(90)) = 0.125 MUg/mL] and
      was superior to levofloxacin (MIC(90) = 1 MUg/mL) and moxifloxacin (MIC(90)=0.25
      MUg/mL). In experimental pneumonia caused by group G S. dysgalactiae subsp.
      equisimilis in mice, the effective dose for 50% survival (ED(50)) of garenoxacin
      following single oral administration was 1.87 mg/kg, >10.7-fold and 4.6-fold less
      than the ED(50) values of levofloxacin (>20 mg/kg) and moxifloxacin (8.54 mg/kg),
      respectively. The area under the free serum concentration-time curve from 0-24 h
      (fAUC(0-24))/MIC ratio of garenoxacin in serum following oral administration of
      20 mg/kg was 73.2, which was 8.7-11.4-fold and 1.4-fold greater than that of
      levofloxacin (6.44-8.46) and moxifloxacin (51.4), respectively. These results
      suggest that garenoxacin has potential for the treatment of infectious diseases
      caused by S. dysgalactiae subsp. equisimilis.

PMID- 21726984
TI  - Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia
      and bacteraemia.
AB  - The bactericidal activity of beta-lactams is determined by the time that
      concentrations in tissue and serum are above the minimum inhibitory concentration
      (T>MIC) for the pathogen. The aim of this study was to compare the probability of
      target attainment (PTA) and the cumulative fraction of response (CFR) for
      meropenem between administration by bolus injection and a 3-h infusion. The study
      was a randomised, three-way, cross-over design in eight febrile neutropenic
      patients with bacteraemia. Each subject received meropenem in three regimens
      consecutively: (i) a bolus injection of 1g every 8 h (q8h) for 24 h; (ii) a 3-h
      infusion of 1 g q8h for 24 h; and (iii) a 3-h infusion of 2 g q8h for 24h. For
      pathogens with an MIC of 4 MUg/mL, the PTA of achieving 40% T>MIC following
      administration of meropenem by a bolus injection of 1g q8h, a 3-h infusion of 1 g
      q8h and a 3-h infusion of 2g q8h was 75.7%, 99.24% and 99.96%, respectively. Only
      the 3-h infusion of 2 g q8h achieved a PTA >99% for 40% T>MIC for a MIC of
      8MUg/mL. By referral to the European Committee on Antimicrobial Susceptibility
      Testing (EUCAST) MIC distributions, the three regimens of meropenem were
      predicted to achieve a CFR>=90% against Escherichia coli and Klebsiella spp. In
      conclusion, a 3-h infusion of 2 g of meropenem q8h resulted in the highest PTA
      rates. The three regimens of meropenem had high probabilities of achieving
      optimal impact against E. coli and Klebsiella spp.

PMID- 21726985
TI  - Investigating the effect of an arterial hypertension drug on the structural
      properties of plasma protein.
AB  - Propanolol is a betablocker drug used in the treatment of arterial hypertension
      related diseases. In order to achieve an optimal performance of this drug it is
      important to consider the possible interactions of propanolol with plasma
      proteins. In this work, we have used several experimental techniques to
      characterise the effect of addition of the betablocker propanolol on the
      properties of bovine plasma fibrinogen (FB). Differential scanning calorimeter
      (DSC), circular dichroism (CD), dynamic light scattering (DLS), surface tension
      techniques and atomic force microscopy (AFM) measurements have been combined to
      carry out a detailed physicochemical and surface characterization of the mixed
      system. As a result, DSC measurements show that propranolol can play two opposite
      roles, either acting as a structure stabilizer at low molar concentrations or as
      a structure destabilizer at higher concentrations, in different domains of
      fibrinogen. CD measurements have revealed that the effect of propanolol on the
      secondary structure of fibrinogen depends on the temperature and the drug
      concentration and the DLS analysis showed evidence for protein aggregation.
      Interestingly, surface tension measurements provided further evidence of the
      conformational change induced by propanolol on the secondary structure of FB by
      importantly increasing the surface tension of the system. Finally, AFM imaging of
      the fibrinogen system provided direct visualization of the protein structure in
      the presence of propanolol. Combination of these techniques has produced
      complementary information on the behavior of the mixed system, providing new
      insights into the structural properties of proteins with potential medical
      interest.

PMID- 21726986
TI  - Highly sensitive voltammetric sensor based on catechol-derivative-multiwall
      carbon nanotubes for the catalytic determination of captopril in patient human
      urine samples.
AB  - A new catechol-derivative compound, N-(3,4-dihydroxyphenethyl)-3,5
      dinitrobenzamide, was synthesized and used to construct a modified-carbon
      nanotubes paste electrode. The electro-oxidation of captopril at the surface of
      the modified electrode was studied using cyclic voltammetry, chronoamperometry,
      and electrochemical impedance spectroscopy. Under the optimized conditions, the
      differential pulse voltammetric peak current of captopril increased linearly with
      captopril concentration in the ranges of 6.4*10(-8) to 3.2*10(-48) mol L(-1). The
      detection limit was 3.4*10(-8) mol L(-1) captopril. The diffusion coefficient and
      kinetic parameters (such as electron transfer coefficient and the heterogeneous
      rate constant) for captopril oxidation were also determined. The RSD% for 0.5 and
      10.0 MUmol L(-1) captopril were 2.1% and 1.6%, respectively. The proposed sensor
      was successfully applied for the determination of captopril in human patient
      urine and tablet samples.

PMID- 21726987
TI  - Spectroscopic approach of the interaction study of amphiphilic drugs with the
      serum albumins.
AB  - The interaction of the amphiphilic drugs, i.e., amitriptyline hydrochloride (AMT)
      and promethazine hydrochloride (PMT), with serum albumins (i.e., human serum
      albumin (HSA) and bovine serum albumin (BSA)), has been examined by the various
      spectroscopic techniques, like fluorescence, UV-vis, and circular dichroism (CD).
      Fluorescence results indicate that in case of HSA-drug complexes the quenching of
      fluorescence intensity at 280 nm is less effective as compared to at 295 nm while
      in case of BSA-drug complexes both have almost same effect and for most of drug
      serum albumin complexes there is only one independent class of binding. For all
      drug-serum albumin complexes the quenching rate constant (K(q)) values suggest
      the static quenching procedure. The UV-vis results show that the change in
      protein conformation of PMT-serum albumin complexes was more prominent as
      compared to AMT-serum albumin complexes. The CD results also explain the
      conformational changes in the serum albumins on binding with drugs. The increase
      in alpha-helical structure for AMT-serum albumin complexes is found to be more as
      compared to PMT-serum albumin complexes. Hence, the various spectroscopic
      techniques provide a quantitative understanding of the binding of amphiphilic
      drugs with serum albumins.

PMID- 21726988
TI  - A Markov decision process approach to multi-category patient scheduling in a
      diagnostic facility.
AB  - OBJECTIVES: To develop a mathematical model for multi-category patient scheduling
      decisions in computed tomography (CT), and to investigate associated tradeoffs
      from economic and operational perspectives. METHODS: We modeled this decision
      problem as a finite-horizon Markov decision process (MDP) with expected net CT
      revenue as the performance metric. The performance of optimal policies was
      compared with five heuristics using data from an urban hospital. In addition to
      net revenue, other patient-throughput and service-quality metrics were also used
      in this comparative analysis. RESULTS: The optimal policy had a threshold
      structure in the two-scanner case - it prioritized one type of patient when the
      queue-length for that type exceeded a threshold. The net revenue gap between the
      optimal policy and the heuristics ranged from 5% to 12%. This gap was 4% higher
      in the more congested, single-scanner system than in the two-scanner system. The
      performance of the net revenue maximizing policy was similar to the heuristics,
      when compared with respect to the alternative performance metrics in the two
      scanner case. Under the optimal policy, the average number of patients that were
      not scanned by the end of the day, and the average patient waiting-time, were
      both nearly 80% smaller in the two-scanner case than in the single-scanner case.
      The net revenue gap between the optimal policy and the priority-based heuristics
      was nearly 2% smaller as compared to the first-come-first-served and random
      selection schemes. Net revenue was most sensitive to inpatient (IP) penalty costs
      in the single-scanner system, whereas to IP and outpatient revenues in the two
      scanner case. CONCLUSIONS: The performance of the optimal policy is competitive
      with the operational and economic metrics considered in this paper. Such a policy
      can be implemented relatively easily and could be tested in practice in the
      future. The priority-based heuristics are next-best to the optimal policy and are
      much easier to implement.

PMID- 21726989
TI  - Impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cutaneous wound healing.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a representative of a large group
      of polyhalogenated aromatic hydrocarbons that are widespread environmental
      contaminants. Administration of TCDD to laboratory animals or cultured cells
      results in a number of adverse effects that are well documented. For example, the
      effects of TCDD observed in developing organisms indicate that exposure to this
      class of environmental contaminants significantly alters embryo morphogenesis.
      However, it is not clear whether tissue regeneration in adult animals may be
      similarly affected. With this in mind, we examined the impact of TCDD exposure on
      wound healing using a murine cutaneous wound healing model. Our results indicate
      that TCDD exposure did not significantly alter the time needed for wound closure.
      However, in the TCDD-treated mice, a significant decrease in tensile strength in
      the healed wounds was observed which is indicative of an aberrantly healed wound.
      Immunostaining revealed that exposure to TCDD increased the population of
      macrophages detected within the wounded tissue at the latter stages of wound
      healing. Our findings support the idea that exposure to environmental
      contaminants such as TCDD is proinflammatory in the wounded tissue, disrupts
      normal healing and ultimately produces in a poorly healed wound.

PMID- 21726990
TI  - A delicate dance: host response to mycobacteria.
AB  - Mycobacterium tuberculosis is an enormously successful human pathogen that can
      infect its host for decades without causing clinical disease, only to reactivate
      when host immunity is compromised. A normal immune response thus contains
      bacterial spread without inducing sterilizing immunity, therefore benefitting
      both host and pathogen. Recent work has begun to outline the complexity of this
      host-pathogen interaction and to reveal how the homeostatic balance between the
      two is achieved. This review focuses on two significant aspects of this delicate
      dance: the host's initial innate response and the mature granuloma that later
      contains the pathogen. Here, we review the fine balance of inflammatory events
      triggered or controlled by both the host and bacteria and implications for the
      survival of each.

PMID- 21726991
TI  - Salmonella typhimurium diarrhea: switching the mucosal epithelium from
      homeostasis to defense.
AB  - The mammalian intestine is a complex biological system composed of the
      epithelium, the gut associated immune system, a commensal microbial community of
      approx. 10(10) cells per gram of content ('microbiota') and an occasional
      onslaught by pathogens. The mechanisms governing homeostasis and immune defense
      are of great importance, but incompletely understood. This is explained by the
      system's sheer complexity. So far, no single study has considered all relevant
      parameters, that is (i) innate and adaptive mucosal immune responses; (ii) mucosa
      cell gene expression; (iii) community composition of the microbiota; (iv)
      microbiota gene expression; (v) genetic profiling of the host; (vi) the virulence
      complement expressed by the pathogen in vivo. This exquisite complexity explains
      why simplified model systems have fuelled much recent progress on the system's
      regulating principles. Here, we focus on one particular model, the streptomycin
      pretreated mouse model for Salmonella diarrhea, to illustrate novel concepts in
      microbe-mucosa interaction, that is how this system switches from homeostasis to
      disease.

PMID- 21726992
TI  - The effect of caffeinated coffee on airway response to methacholine and exhaled
      nitric oxide.
AB  - BACKGROUND: The bronchoprotective effect of caffeine on histamine challenge
      testing (HCT) has been studied with equivocal results. Current guidelines for
      bronchoprovocation testing recommend exclusion of caffeine the day of testing.
      The effects of caffeine on methacholine challenge testing (MCT), now more
      commonly performed than histamine challenge, are unknown. METHODS: Sixteen well
      controlled asthmatics with a forced expiratory volume in 1 s (FEV(1)) > 65%
      predicted and methacholine provocation concentration causing a 20% fall in FEV(1)
      (PC(20)) <= 16 mg/ml participated in a randomized single-blind crossover study.
      The two treatments included 16 ounces of caffeinated and decaffeinated coffee
      given on two separate days. The fraction of exhaled nitric oxide (eNO) and FEV(1)
      were measured before and 1 h after each treatment. One hour post treatment blood
      was drawn for serum caffeine level and the MCT was done. RESULTS: Fourteen
      subjects completed the study; there were no adverse events. No significant
      bronchodilation was seen between the mean FEV(1) values before and after the
      caffeinated treatment (3.31 +/- 0.75 L and 3.36 +/- 0.74 L, respectively). No
      significant bronchoprotection was seen between the caffeinated and decaffeinated
      treatment's geometric mean PC(20) values (1.35 mg/ml and 1.36 mg/ml,
      respectively). Mean eNO values before and after caffeinated treatment were not
      significantly different (31.2 +/- 19.6 ppb and 31.5 +/- 20.4 ppb). CONCLUSION:
      The amount of caffeine in a normal dietary serving of a 16 oz cup of coffee is
      not enough to cause significant bronchoprotection, bronchodilation, or decrease
      eNO values. Registered at http://clinicaltrials.gov: NCT01057875.

PMID- 21726993
TI  - An artificial enzyme-based assay: DNA detection using a peroxidase-like copper
      creatinine complex.
AB  - We report an artificial enzyme-based DNA assay using a peroxidase-like copper
      (Cu)-creatinine complex as a catalyst for 3,3',5,5'-tetramethylbenzidine (TMB)
      oxidation. The assay employs double signal amplification and a homogeneous
      catalytic reaction: (i) fast catalytic growth of Cu on a gold (Au) nanoparticle
      (NP) label forms a thick Cu layer (first amplification); (ii) dissolution of the
      Cu layer generates many Cu-creatinine complexes per NP (generation of homogeneous
      catalysts); (iii) peroxidase-like Cu-creatinine complexes rapidly convert TMB
      into a colored product (second amplification). To investigate the effect of
      ligand on the catalytic activities of Cu complexes, the kinetics of catalytic TMB
      oxidation is tested with and without using imidazole ring-containing ligands
      (creatinine, imidazole, and poly(l-histidine)). Both fast oxidation of TMB and
      slow further oxidation of the colored product are required for high signal-to
      background ratios. Cu-creatinine complex allows relatively fast oxidation and
      slow further oxidation. Fast seed-mediated Cu growth on Au NP and slow Cu
      autonucleation (i.e., slow formation of Cu NP in the absence of Au NP) are also
      required for high signal-to-background ratios. In tris-EDTA
      (tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetic acid) buffer (pH 7.7)
      containing high concentrations of Cu(2+) (90 mM), ascorbic acid (50mM), and
      Mg(2+) (200 mM), Cu growth on Au NP is very fast and autonucleation is
      significantly suppressed. Fast catalytic oxidation by Cu-creatinine complex along
      with fast Cu growth on Au NP allows a detection limit of 0.1 pM for DNA in a
      simple microplate format.

PMID- 21726994
TI  - Microscale mesoarrays created by dip-pen nanolithography for screening of protein
      protein interactions.
AB  - Using microarrays to probe protein-protein interactions is becoming increasingly
      attractive due to their compatibility with highly sensitive detection techniques,
      selectivity of interaction, robustness and capacity for examining multiple
      proteins simultaneously. The major drawback to using this approach is the
      relatively large volumes and high concentrations necessary. Reducing the protein
      array spot size should allow for smaller volumes and lower concentrations to be
      used as well as opening the way for combination with more sensitive detection
      technologies. Dip-Pen Nanolithography (DPN) is a recently developed technique for
      structure creation on the nano to microscale with the capacity to create
      biological architectures. Here we describe the creation of miniaturised
      microarrays, 'mesoarrays', using DPN with protein spots 400* smaller by area
      compared to conventional microarrays. The mesoarrays were then used to probe the
      ERK2-KSR binding event of the Ras/Raf/MEK/ERK signalling pathway at a physical
      scale below that previously reported. Whilst the overall assay efficiency was
      determined to be low, the mesoarrays could detect KSR binding to ERK2 repeatedly
      and with low non-specific binding. This study serves as a first step towards an
      approach that can be used for analysis of proteins at a concentration level
      comparable to that found in the cellular environment.

PMID- 21726995
TI  - Non-immunoglobulin based protein scaffolds.
AB  - Non-immunoglobulin based protein scaffolds have been reported as promising
      alternatives to traditional monoclonal antibodies for over a decade and are often
      mentioned as part of the next-generation immunotherapeutics. Today, this class of
      biologics is beginning to demonstrate its potential for therapeutic applications
      and several are currently in preclinical or clinical development. A common
      denominator for most of these new scaffolds is the attractive properties that
      differentiate them from monoclonal antibodies including small size, cysteine-free
      sequence, flexible pharmacokinetic properties, and ease of generating
      multispecific molecules. In addition to therapeutic applications, substantial
      evidence point to superior performance of several of these scaffolds in molecular
      imaging compared to full-length antibodies. Here we review the most recent
      progress using alternative protein scaffolds for therapy and medical imaging.

PMID- 21726996
TI  - Immuno-imaging using nanobodies.
AB  - Immuno-imaging is a developing technology that aims at studying disease in
      patients using imaging techniques such as positron emission tomography in
      combination with radiolabeled immunoglobulin derived targeting probes. Nanobodies
      are the smallest antigen-binding antibody-fragments and show fast and specific
      targeting in vivo. These probes are currently under investigation as therapeutics
      but preclinical studies indicate that nanobodies could also become the next
      generation of magic bullets for immuno-imaging. Initial data show that imaging
      can be performed as early as 1 hour post-injection enabling the use of short
      lived radio-isotopes. These unique properties should enable patient friendly and
      safe imaging protocols. This review focuses on the current status of radiolabeled
      nanobodies as targeting probes for immuno-imaging.

PMID- 21726997
TI  - Death receptor 5 and cellular FLICE-inhibitory protein regulate pemetrexed
      induced apoptosis in human lung cancer cells.
AB  - Pemetrexed is a clinically available anti-folate therapeutic agent used in
      combination with cisplatin for the management of patients with malignant pleural
      mesothelioma and advanced non-small cell lung cancer. Pemetrexed inhibits three
      enzymes in purine and pyrimidine synthesis necessary for precursor DNA
      nucleotides which in turn disrupts growth and survival of normal and cancer
      cells. The mechanism by which pemetrexed induces apoptosis remains largely
      uncharacterised. In the current study, we examined the downstream effect of
      pemetrexed in inducing apoptosis in lung cancer cells. We showed that pemetrexed
      induced apoptosis via up-regulation of Death Receptor 5 (DR5), an important death
      receptor for tumour necrosis factor (TNF)-related apoptosis inducing ligand
      (TRAIL). In addition, we discovered a synergistic effect of combination
      pemetrexed and recombinant TRAIL in inducing apoptosis. Modulating DR5 induction
      by small interfering RNA abrogated the ability of pemetrexed to induce apoptosis.
      In addition, silencing of C/EBP homologous protein (CHOP) expression reduced DR5
      expression, demonstrating that the transcriptional factor CHOP has a pivotal role
      on DR5 up-regulation following pemetrexed treatment. In addition, enforced
      expression of cellular FLICE-inhibitory protein (c-FLIP), a known inhibitor of
      caspase 8, protected neoplastic cells from apoptosis despite pemetrexed and/or
      TRAIL therapy. Thus, our findings demonstrate the efficacy and mechanistic
      underpinnings of pemetrexed-induced apoptosis, and they suggest pemetrexed may
      have clinical utility when used in combination with TRAIL for the management of
      patients with lung cancer.

PMID- 21726998
TI  - Radiochemotherapy versus surgery plus radio(chemo)therapy for stage T3/T4 larynx
      and hypopharynx cancer - results of a matched-pair analysis.
AB  - The standard treatment for non-metastatic T3/T4 larynx and hypopharynx cancer
      varies. This study compared definitive radiochemotherapy to surgery followed by
      radio(chemo)therapy. Forty-four patients treated with radiochemotherapy were
      matched to 88 patients receiving surgery plus radio(chemo)therapy. Groups were
      matched 1:2 for eight factors including age, gender, performance status, tumour
      site, histologic grade, T-/N-category and AJCC stage. Groups were compared for
      loco-regional control, metastases-free survival, overall survival and toxicity.
      Two-year loco-regional control rates were 75% after surgery plus
      radio(chemotherapy) and 66% after radiochemotherapy (p=0.39). Metastases-free
      survival rates were 76% and 77%, respectively (p=0.76). Overall survival rates
      were 67% and 63%, respectively (p=0.95). During follow up, 60% and 9% of the
      patients, respectively, received a total laryngectomy (p=0.004). Grade >=3 oral
      mucositis and haematologic toxicity rates were higher with radiochemotherapy.
      Other toxicities were similar. Outcomes of radiochemotherapy appeared similar to
      those of surgery plus radio(chemo)therapy. The larynx preservation rate was
      higher after radiochemotherapy.

PMID- 21726999
TI  - Swedish lung cancer radiation study group: predictive value of histology for
      radiotherapy response in patients with non-small cell lung cancer.
AB  - The aim of the present study was to evaluate the potential predictive value of
      histology in non-small cell lung cancer (NSCLC) treated with curatively intended
      radiotherapy. In a collaborative effort among all the Swedish Oncology
      Departments, clinical data were collected for 1146 patients with a diagnosed non
      small cell lung cancer subjected to curatively intended irradiation (?50 Gy)
      during the years 1990 to 2000. The included patients were identified based on a
      manual search of all medical and radiation charts at the oncology departments
      from which the individual patient data were collected. Only patients who did not
      have a histological diagnosis date and death date/last follow-up date were
      excluded (n=141). Among the 1146 patients with non-small cell carcinoma eligible
      for analysis, 919 were diagnosed with either adenocarcinoma (n=323) or squamous
      cell carcinoma (n=596) and included in this study. The median survival for the
      919 patients was 14.8 months, while the 5-year survival rate was 9.5%. Patients
      with adenocarcinoma had a significantly better overall survival compared with
      patients with squamous cell carcinoma (p=0.0062, log-rank test). When comparing
      different stages, this survival benefit was most pronounced for stages IIA-IIB
      (p<0.0001, log-rank test). The difference in survival between the two
      histological groups was statistically significant in a univariate Cox analysis
      (p=0.0063) as well as in two multivariate Cox analyses including demographic and
      treatment variables (p=0.037 and p=0.048, respectively). In this large population
      based retrospective study we describe for the first time that patients with
      adenocarcinoma have a better survival after curatively intended radiation therapy
      in comparison with squamous cell carcinoma patients, particularly those with
      clinical stages IIA-IIB.

PMID- 21727000
TI  - Isolation and characterization of a fungus able to degrade pyrethroids and 3
      phenoxybenzaldehyde.
AB  - Fungal strain HU, isolated from activated sludge and identified as a member of
      the genus Cladosporium based on morphology and sequencing of 28S rRNA, was shown
      to degrade 90% of fenvalerate, fenpropathrin, beta-cypermethrin, deltamethrin,
      bifenthrin, and permethrin (100 mgL(-1)) within 5 days. Fenvalerate was utilized
      as sole carbon and energy source and co-metabolized in the presence of sucrose.
      Degradation of fenvalerate occurred at pH 5-10 at 18-38 degrees C. The fungus
      first hydrolyzed the carboxylester linkage to produce alpha-hydroxy-3-phenoxy
      benzeneacetonitrile and 3-phenoxybenzaldehyde, and subsequently degraded these
      two compounds with a q(max), K(s) and K(i) of 1.73 d(-1), 99.20 mgL(-1) and
      449.75 mgL(-1), respectively. Degradation followed first-order kinetics. These
      results show that the fungal strain may possess potential to be used in
      bioremediation of pyrethroid-contaminated environments.

PMID- 21727001
TI  - Enhanced resistance of Saccharomyces cerevisiae to vanillin by expression of lacA
      from Trametes sp. AH28-2.
AB  - Saccharomyces cerevisiae is affected by the presence of certain phenolic
      compounds such as vanillin during fermentation of pretreated lignocellulosic
      hydrolysates. Since vanillin can be polymerized in the presence of laccase into
      compounds with lower toxicity, the laccase gene, lacA, from Trametes sp. AH28-2
      was fused to the alpha-factor signal sequence and transferred into S. cerevisiae
      CEN.PK strains for secretory expression. Furthermore, the chaperone gene, KAR2,
      was overexpressed to promote the translocation of laccase. In the presence of 8
      mmol/L vanillin, a shorter lag phase was observed in the lacA gene expressing
      strains. The vanillin-specific conversion rate of the lacA-expressing strain
      BSJX0A2 was 0.069 g g(-1)biomass h(-1), while it was 0.065 g g(-1)biomass h(-1)
      in the reference strain.

PMID- 21727002
TI  - Biogas production and saccharification of Salix pretreated at different steam
      explosion conditions.
AB  - Different steam explosion conditions were applied to Salix chips and the effect
      of this pretreatment was evaluated by running both enzymatic hydrolysis and
      biogas tests. Total enzymatic release of glucose and xylose increased with
      pretreatment harshness, with maximum values being obtained after pretreatment for
      10 min at 210 degrees C. Harsher pretreatment conditions did not increase glucose
      release, led to degradation of xylose and to formation of furfurals. Samples
      pretreated at 220 and 230 degrees C initially showed low production of biogas,
      probably because of inhibitors produced during the pretreatment, but the
      microbial community was able to adapt and showed high final biogas production.
      Interestingly, final biogas yields correlated well with sugar yields after
      enzymatic hydrolysis, suggesting that at least in some cases a 24h enzymatic
      assay may be developed as a quick method to predict the effects of pretreatment
      of lignocellulosic biomass on biogas yields.

PMID- 21727003
TI  - Effect of feeding and sludge age on acclimated bacterial community and fate of
      slowly biodegradable substrate.
AB  - The study investigated the effect of feeding regime and sludge age on starch
      utilization. For this purpose, parallel sequencing batch reactors were operated
      with pulse and continuous feeding of soluble starch at sludge ages of 8 and 2
      days. Pulse feeding induced almost complete conversion of starch to glycogen,
      while storage was lowered and accompanied with direct growth under continuous
      feeding, regardless of sludge age. Low sludge age did not alter simultaneous
      storage and utilization for direct growth but it slightly favoured direct
      utilization due to faster growing biomass. Experimental results suggested
      adsorption of starch onto biomass as a preliminary removal mechanism prior to
      hydrolysis at sludge age of 8 days. Adsorption was not noticeable as substrate
      removal, glycogen generation and dissolved oxygen decrease were synchronous at
      sludge age of 2 days. Bacterial community always included fractions storing
      glycogen although sludge age only affected the relative magnitude of filamentous
      growth.

PMID- 21727004
TI  - Microwave, ultrasonic and chemo-mechanical pretreatments for enhancing methane
      potential of pulp mill wastewater treatment sludge.
AB  - Microwave (2450 MHz, 1250 W), ultrasonic (20 kHz, 400 W) and chemo-mechanical
      (MicroSludge(r) with 900 mg/L NaOH followed by 83,000 kPa) pretreatments were
      applied to pulp mill waste sludge to enhance methane production and reduce
      digester sludge retention time. The effects of four variables (microwave
      temperature in a range of 50-175 degrees C) and sonication time (15-90 min),
      sludge type (primary or secondary) and digester temperature (mesophilic and
      thermophilic) were investigated. Microwave pretreatment proved to be the most
      effective, increasing specific methane yields of WAS samples by 90% compared to
      controls after 21 days of mesophilic digestion. Sonication solubilized the sludge
      samples better, but resulted in soluble non-biodegradable compounds. Based on the
      laboratory scale data, MicroSludge(r) was found the least energy intensive
      pretreatment followed by sonication for 15 min alternative with net energy
      profits of 1366 and 386 kWh/tonne of total solids (TS), respectively.
      Pretreatment benefits were smaller for thermophilic digesters.

PMID- 21727005
TI  - Intragenic rearrangements in LARGE and POMGNT1 genes in severe
      dystroglycanopathies.
AB  - Dystroglycanopathies are a heterogeneous group of muscular dystrophies with
      autosomal recessive inheritance characterized by abnormal glycosylation of alpha
      dystroglycan. The most severe phenotypes are Walker-Warburg Syndrome (WWS) and
      muscle-eye-brain disease (MEB) presenting with lissencephaly type II (LIS II) and
      in which muscular dystrophy is associated with mental retardation and eye
      abnormalities. To date, six distinct genes, POMT1, POMT2, POMGNT1, FKTN, FKRP,
      LARGE and recently in one case DPM3, have been shown to be involved in
      dystroglycanopathies. Genomic sequencing alone is still frequently used for
      diagnosis purpose, not allowing detection of intragenic rearrangements at the
      heterozygous state contrarily to RNA analysis, quantitative PCR and CGH array
      analysis. These latter methods enabled us to identify four new intragenic
      rearrangements in the LARGE gene in three fetuses with WWS, born to two unrelated
      families: deletion of exons 9-10 and duplication of introns 1-4 for the first
      family and deletion of exons 4 and 7 for the second one; and a deletion of the
      last six exons of the POMGNT1 gene in two unrelated MEB patients. Genomic dosage
      studies using emerging tools such as CGH array should be included in routine
      molecular analysis of dystroglycanopathies, not only for the screening of the
      LARGE gene in which this kind of mutation seems to be more frequent than point
      mutations, but also for the other involved genes, especially in severe clinical
      cases.

PMID- 21727006
TI  - Renal safety of ibandronate 6 mg infused over 15 min versus 60 min in breast
      cancer patients with bone metastases: a randomized open-label equivalence trial.
AB  - PURPOSE: The aim of this study was to demonstrate the renal safety equivalence of
      ibandronate 6 mg infused over 15 min versus 60 min, in patients with bone
      metastases of breast cancer. PATIENTS AND METHODS: Patients were females having
      breast cancer with at least one bone metastasis. Exclusion criteria were renal
      failure (creatinine clearance < 30 mL/min), tooth/jaw disorder or uncontrolled
      severe disease. Eligible patients were randomly assigned to receive nine
      ibandronate 6 mg i.v. infusions over either 15 min or 60 min. The primary outcome
      was the 95% confidence interval (CI) of the difference in creatinine clearance
      between groups, 28 days after the last infusion. The equivalence margin was +/-8
      mL/min. RESULTS: Overall 334 patients were randomized (165-15 min infusions vs.
      169 to 60 min infusions, 325 (159 vs. 166) were analyzed by intent-to-treat, and
      312 (151 vs. 161) were analyzed per protocol. Per protocol, the 15 min-60 min
      difference in creatinine clearance [95% CI] was -3.00 [-8.18, 2.18]. By intent-to
      treat, this difference was-2.91 [-7.99, 2.16]. Death and serious adverse event
      rates did not differ between groups. Three serious adverse events were considered
      related to ibandronate: an osteonecrosis of the jaw (15-min group), a pain in jaw
      and an enamel cracking (60-min group). Two renal failures, reported in the 60 min
      group, were not considered related to ibandronate. None occurred in the 15 min
      group. CONCLUSION: Ibandronate may be infused over 15 min without clinically
      significant consequence on renal safety.

PMID- 21727008
TI  - On the filtering of intersegmental loads during running.
AB  - When performing inverse dynamics analysis, smoothing kinematic and force platform
      data at different cutoff frequencies creates an "impact" like artifact that is
      visible in the joint moments during impulsive activity. Here we illustrate a
      processing technique in which inverse dynamics analysis is performed on the raw
      kinematic and force platform data and the joint reaction forces and moments are
      subsequently smoothed based on the frequency content of the distal reaction
      force. The effectiveness of this technique is illustrated on forward dynamics
      simulation data with known intersegmental loads. We then apply the technique to
      an experimental data set of 10 subjects running at three prescribed speeds. We
      show that performing inverse dynamics on the raw data and subsequently smoothing
      the intersegmental loads results in minimal attenuation of the joint reaction
      force and avoids impact artifacts in the joint moments. Artifacts that occur
      using a traditional filtering technique are systematic, become more pronounced
      with speed, and are most noticeable at the hip joint.

PMID- 21727007
TI  - Biological hydrogels as selective diffusion barriers.
AB  - The controlled exchange of molecules between organelles, cells, or organisms and
      their environment is crucial for life. Biological gels such as mucus, the
      extracellular matrix (ECM), and the biopolymer barrier within the nuclear pore
      are well suited to achieve such a selective exchange, allowing passage of
      particular molecules while rejecting many others. Although hydrogel-based filters
      are integral parts of biology, clear concepts of how their barrier function is
      controlled at a microscopic level are still missing. We summarize here our
      current understanding of how selective filtering is established by different
      biopolymer-based hydrogels. We ask if the modulation of microscopic particle
      transport in biological hydrogels is based on a generic filtering principle which
      employs biochemical/biophysical interactions with the filtered molecules rather
      than size-exclusion effects.

PMID- 21727009
TI  - Bonner sphere spectrometer for characterization of BNCT beam.
AB  - The characterization of the epithermal beam is performed by different dosimetry
      techniques that give information on neutron flux as well as neutron and photon
      doses. One of the possible methods is based on the measurement of thermal
      neutrons in a moderation environment, which enables the evaluation of neutron
      flux in a group structure and also neutron dose. The advantage of such a
      spectrometer consists of the fact that 90% response intervals of the spheres
      continuously cover the epithermal part of the neutron energy range. The method
      has been applied to characterize the epithermal neutron beams at several research
      centers in USA, Finland, the Netherlands and Czech Republic. The comparison of
      the MIT FCB, HFR HB11, VTT FiR, and LVR-15 beam parameters is presented in this
      paper.

PMID- 21727010
TI  - Simplified two media method: a modified approach for measuring linear attenuation
      coefficient of odd shaped archaeological samples of unknown thickness.
AB  - Linear attenuation coefficients of regular as well as irregular shaped
      archaeological samples of FaLG (flyash-lime-gypsum) of unknown thickness have
      been measured employing 'simplified two media' method. Seven different liquid
      materials plus air have been used as media to measure attenuation coefficient of
      these samples. Obtained results have been compared with those for regular shaped
      samples. Experimental values have also been compared with theoretical values
      calculated from FFAST and XCOM. A good agreement has been observed between
      experimental and theoretical values. Present measurements employing 'simplified
      two media' method have been reported for the first time for checking its
      validation and reliability.

PMID- 21727011
TI  - The evaluation of the nasal morphologic changes after bimaxillary surgery in
      skeletal class III maloccusion by using the superimposition of cone-beam computed
      tomography (CBCT) volumes.
AB  - BACKGROUND: The purpose of this study was to evaluate nasal morphologic and
      maxillary skeletal changes occurring after bimaxillary surgery in skeletal class
      III patients, using a new method entailing superimposition of cone-beam computed
      tomography (CBCT) volumes. MATERIALS & METHODS: The subjects consisted of 30
      adults (15 males and 15 females) who had presented with skeletal class III
      deformities. The subjects underwent Le Fort I advancement and impaction osteotomy
      and mandibular setback surgery. For closure of the maxillary vestibular incision,
      alar cinch suture and V-Y closure were performed. The pre- and post-operative
      CBCT data were superimposed and evaluated by voxel-by-voxel registration.
      RESULTS: After surgery, the nasolabial angle, nasal tip angle, nasal tip
      inclination and columellar angle showed significant increases (P < 0.01). The
      nasal tip protrusion and nasal height, meanwhile, had significantly decreased (P
      < 0.01), and the alar base width had increased (P < 0.01). The columellar length
      and nostril axis angle also had decreased, but the nostril area did not show any
      significant change. CONCLUSIONS: After surgery, as the maxilla had been moved
      upward and forward, the nasal tip was shifted antero-superiorly and the alar base
      width and nostrils were widened. CBCT superimposition, enabling 3D assessment of
      nasal morphologic changes, can be an effective tool for simultaneous measurement
      of skeletal and soft-tissue changes.

PMID- 21727012
TI  - Outcome and survival analysis of pulmonary metastasectomy for hepatocellular
      carcinoma.
AB  - OBJECTIVE: The lung is the most common site for extrahepatic metastasis from
      hepatocellular carcinoma (HCC). We previously reported in a series of 20 patients
      that pulmonary metastasectomy for HCC is feasible in selected patients. The
      objective of this study was to re-evaluate the long-term outcomes and prognostic
      factors with an additional 25 patients. METHODS: We retrospectively analyzed the
      records of 45 consecutive patients who underwent pulmonary metastasectomy due to
      HCC at our institution between 1990 and 2010. RESULTS: Thirty-nine patients
      underwent hepatectomy or liver transplantation, whereas six patients underwent
      locoregional therapy for primary liver lesions. Twenty-seven patients died during
      a median 17.6-month follow-up period. The 2-year disease-free survival (DFS) was
      19.5%. The 5-year overall survival (OS) was 40.9%. History of recurrence and
      serum des-gamma-carboxy prothrombin (DCP) level >40 mAU ml(-1) at initial
      pulmonary resection were unfavorably associated with OS in univariate analysis.
      CONCLUSIONS: Pulmonary metastasectomy for HCC in selected patients resulted in
      relatively good outcomes with regard to OS. History of recurrence and serum DCP
      levels were shown to be candidates of prognostic factors for OS.

PMID- 21727013
TI  - Selection against canine hip dysplasia: success or failure?
AB  - Canine hip dysplasia (CHD) is a multifactorial skeletal disorder which is very
      common in pedigree dogs and represents a huge concern for canine welfare. Control
      schemes based on selective breeding have been in operation for decades. The aim
      of these schemes is to reduce the impact of CHD on canine welfare by selecting
      for reduced radiographic evidence of CHD pathology as assessed by a variety of
      phenotypes. There is less information regarding the genotypic correlation between
      these phenotypes and the impact of CHD on canine welfare. Although the phenotypes
      chosen as the basis for these control schemes have displayed heritable phenotypic
      variation in many studies, success in achieving improvement in the phenotypes has
      been mixed. There is significant room for improvement in the current schemes
      through the use of estimated breeding values (EBVs), which can combine a dog's
      CHD phenotype with CHD phenotypes of relatives, other phenotypes as they are
      proven to be genetically correlated with CHD (especially elbow dysplasia
      phenotypes), and information from genetic tests for population-relevant DNA
      markers, as such tests become available. Additionally, breed clubs should be
      encouraged and assisted to formulate rational, evidenced-based breeding
      recommendations for CHD which suit their individual circumstances and dynamically
      to adjust the breeding recommendations based on continuous tracking of CHD
      genetic trends. These improvements can assist in safely and effectively reducing
      the impact of CHD on pedigree dog welfare.

PMID- 21727014
TI  - Biomechanical evaluation of a novel nucleus pulposus prosthesis in canine
      cadaveric spines.
AB  - Partial disc replacement is a new surgical technique aimed at restoring
      functionality to degenerated intervertebral discs (IVDs). The aim of the present
      study was to assess biomechanically the behaviour of a novel nucleus pulposus
      prosthesis (NPP) in situ and its ability to restore functionality to the canine
      IVD after nuclectomy alone or after combined dorsal laminectomy and nuclectomy.
      Nine canine T13-L5 specimens (L2L3 group) and 10 L5-Cd1 specimens (LS group) were
      tested biomechanically in the native state, after nuclectomy (L2L3 group) or
      after combined dorsal laminectomy and nuclectomy (LS group), and after insertion
      of the NPP. Range of motion (ROM), neutral zone (NZ), and neutral zone stiffness
      (NZS) were determined in flexion/extension, lateral bending, and axial rotation.
      Nuclectomy alone and combined dorsal laminectomy and nuclectomy caused
      significant instability in all motion directions. Implantation of the NPP
      resulted in significant restoration of the parameters (ROM, NZ, and NZS) towards
      the native state; however, fragmentation/herniation of the NPP occurred in 47% of
      the cases. In conclusion, the NPP has the ability to improve functionality of the
      nuclectomized canine IVD. The high rate of NPP failure requires modifications
      directed at the integrity of the NPP and its confinement to the nuclear cavity.

PMID- 21727015
TI  - Role of the omega loop in specificity determination in subsite 2 of the D
      alanine:D-alanine (D-lactate) ligase from Leuconostoc mesenteroides: a molecular
      docking study.
AB  - The synthesis of D-ala-D-lactate in Leuconostoc mesenteroides is catalyzed by D
      alanine:D-alanine (D-lactate) ligase (ADP). The ability to assemble this
      depsipeptide as well as D-ala-D-ala provides a mechanism for the organism's
      intrinsic resistance to vancomycin. Mutation of Phe261 to Tyr261 in the Omega
      loop of this ligase showed a complete loss of the ability to make D-ala-D-lactate
      (Park and Walsh, J. Biol. Chem. 272 (1997) 9210-9214). Phe261 is a key
      specificity determinant in the alpha-helical cap of the Omega-loop when folded
      into the closed conformation. A molecular docking study of the closed ligase
      using AutoDock 4.2 defines additional specificity constraints promoted by the
      Omega-loop capping the catalytic center. Attaining productive orientations of D
      lactate with favorable ligation chemistry requires the flexibilities of Phe261
      and Arg301 in the docking protocol. These are in addition to the optimization of
      van der Waals contacts with Lys260, Met326, and Ser327. The location of Phe261
      and Lys260 in the alpha-helical cap of the Omega-loop over subsite 2 is an
      essential part of the folding process ensuring depsipeptide formation in the
      hydrophobic environment of the catalytic center. The importance of the F261Y
      mutation suggests that the hydroxyl of Tyr261 plays an instrumental role in
      determining non-productive docking orientations of D-lactate. Two of these are
      presented: (A) D-lactate-OH as an H-bond donor to the Tyr261-OH; (B) D-lactate as
      an H-bond donor to the phosphoryl of the intermediate D-alanyl phosphate, and the
      D-lactate-COO- as an H-bond acceptor for the Tyr261-OH. Neither orientation, A or
      B, show the bifurcated H-bonding with Arg301 recently proposed for the activation
      of the nucleophilic D-lactate for D-ala-D-lactate formation. Insights into the
      role of the Omega-loop and its K(F/Y) signature provide additional background for
      inhibitor design targeted to subsite 2 of the D-alanine:D-alanine (D-X) ligases.

PMID- 21727016
TI  - Sacroiliac edema by MRI does not always indicate spondylarthritis.

PMID- 21727017
TI  - Mechanic's hands.

PMID- 21727018
TI  - Buschke-Ollendorf syndrome in a patient with terminal renal failure.

PMID- 21727019
TI  - Decreased bone mineral density in adult patients with muscular dystrophy.

PMID- 21727020
TI  - Factors associated with rapid progression to knee arthroplasty: complete analysis
      of three-year data from the osteoarthritis initiative.
AB  - OBJECTIVES: Only a few studies have identified prognostic factors indicating risk
      of future knee arthroplasty in patients with osteoarthritis (OA) of the knee. The
      Osteoarthritis Initiative (OAI) is a National Institutes of Health and privately
      funded cohort study of 4796 persons with or at high risk of knee OA. The OAI is
      ideally suited to a more extensive study of knee arthroplasty prognostic factors
      than has been undertaken. The purpose of our study was to identify patient
      factors which predict rapid progression to knee arthroplasty, defined as
      arthroplasty within three years of baseline data collection. METHODS: We used
      alternating logistic regression models to analyze complete three year follow-up
      data from the OAI on 4670 persons with, or at risk for knee OA, aged 45 to 79
      years during the years 2004 to 2008. RESULTS: A total of 128 knees (116 persons)
      underwent knee arthroplasty during the study period. After adjusting for known
      prognostic factors, several previously unidentified predictors of future knee
      arthroplasty were found including past history of knee surgery (RR=2.04, 95%
      CI=1.33, 3.13), knee flexion contracture in degrees (RR=1.06, 95% CI=1.02, 1.11)
      and pain, on a 0 to 10 scale, with active knee flexion (RR=1.58, 95% CI=1.04,
      2.39). DISCUSSION/CONCLUSIONS: This study identifies new and easily measured
      clinical variables that are associated with more rapid progression to
      arthroplasty. The data may help to inform both physicians and patients of medical
      history and clinical examination findings most highly associated with short-term
      arthroplasty.

PMID- 21727021
TI  - A novel polyol method to synthesize colloidal silver nanoparticles by ultrasonic
      irradiation.
AB  - A polyol synthesis of silver nanoparticles in the presence of ultrasonic
      irradiation was compared with other configurations (at ambient temperature, 120
      degrees  C, and 120  degrees C with injected solutions) in the absence of
      ultrasonic irradiation in order to obtain systematic results for morphology and
      size distribution. For applying ultrasonic irradiation, rather fine and uniform
      spherical silver particles (21+/-3.7 nm) were obtained in a simple (at ambient
      temperature without mechanical stirring) and fast (within 4 min, 3.61*10(-3) mol
      min(-1)) manner than other cases (at ambient temperature (for 8 h, 0.03*10(-3)
      mol min(-1)): 86+/-16.8 nm, 120  degrees C (for 12 min, 1.16*10(-3) mol min(-1)):
      64+/-14.9 nm, and 120  degrees C with injected solutions (during 12 min): 35+/
      6.8 nm; all other cases contained anisotropic shaped particles). Even though the
      temperature of polyol reaction reached only at 80  degrees C (<120  degrees C) in
      the presence of ultrasonic irradiation, a uniform mixing (i.e. enhanced collision
      between silver particle and surrounding components) by ultrasonic irradiation
      might induce a better formation kinetics and morphological uniformity.

PMID- 21727022
TI  - Out-of-hospital births and the supply of maternity units in France.
AB  - Maternity unit closures in France have increased distances that women travel to
      deliver in hospital. We studied how the supply of maternity units influences the
      rate of out-of-hospital births using birth certificate data. In 2005-6, 4.3 per
      1000 births were out-of-hospital. Rates were more than double for women living
      30km or more from their nearest unit and were even higher for women of high
      parity. These associations persisted in multilevel analyses adjusting for other
      maternal characteristics. Long distances to maternity units should be a concern
      to health planners because of the maternal and infant health risks.

PMID- 21727023
TI  - Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion
      of activin A.
AB  - Myofibroblasts are essential during wound healing and are often found in the
      stroma of oral squamous cell carcinomas (OSCC). Although the molecular mechanisms
      by which myofibroblasts influence OSCC remain largely unknown, previous studies
      demonstrated that presence of myofibroblast in OSCC stroma is an important risk
      factor of patient's shortened survival. Here we showed that some growth factors
      are produced in higher levels by tumor-associated myofibroblasts compared to
      tumor-associated fibroblasts, including activin A. Myofibroblast-conditioned
      media containing activin A significantly increased OSCC cell proliferation and
      tumor volume, whereas down-regulation of activin A in the conditioned media
      decreased proliferation. In addition, myofibroblasts induced in vitro invasion of
      OSCC cells, which was accompanied by an increased production of matrix
      metalloproteinases (MMP). In vivo, a significant correlation between presence of
      myofibroblasts and activities of MMP-2 and MMP-9 was observed in OSCC samples.
      However, blockage of activin A synthesis by myofibroblasts did not affect
      invasion and MMP production by OSCC cells. Together, our data demonstrate that
      activin A is required for the proliferative effects of myofibroblasts on OSCC
      cells. We conclude that myofibroblasts in the stroma of OSCC may influence
      proliferation and invasion, resulting in more aggressive tumor.

PMID- 21727024
TI  - Elective versus therapeutic neck dissection in the clinically node negative neck
      in early oral cavity cancers: do we have the answer yet?

PMID- 21727025
TI  - Interictal high frequency oscillations (HFOs) in patients with focal epilepsy and
      normal MRI.
AB  - OBJECTIVE: We aim to analysis the relationship between HFOs-generating regions
      and the seizure onset zone (SOZ) in epileptic patients without a visible lesion
      on MRI. METHODS: Intracerebral EEGs were recorded in 17 patients with intractable
      focal seizures and normal MRIs. The rates of interictal HFOs and spikes inside
      and outside the SOZ were analyzed as well as the specificity, sensitivity and
      accuracy of HFOs and spikes to determine the SOZ. RESULTS: The mean rate of
      spikes, ripples and fast ripples (FR) was higher in the SOZ than in the non-SOZ
      channels. In regard to the identification of the SOZ the sensitivity was 91% for
      spikes, 91% for ripples and 66% for FR, the specificity was 30% for spikes, 42%
      for ripples and 80% for FR, and the accuracy was 44% for spikes, 54% for ripples
      and 76% for FR. CONCLUSIONS: The rates of spikes and HFOs were higher inside than
      outside the SOZ. However, HFOs are also more specific and accurate than spikes to
      delineate the SOZ. SIGNIFICANCE: Analysis of interictal HFOs during 5-10 min of
      sleep recording is a good tool to localize the SOZ in patients with epilepsy and
      normal MRI, and could potentially reduce the duration of chronic intracerebral
      EEG recordings.

PMID- 21727026
TI  - G-protein coupled receptors regulating cough.
AB  - Cough is a protective mechanism but can occur excessively in disease. Cough can
      be modulated by a range of GPCRs which can be either inhibitory or excitatory.
      Prostaglandin E2 and bradykinin can activate airway sensory nerves via EP3 and B2
      receptors receptively and have both been shown to mediate their effects though
      TRPV1 and TRPA1 receptors. Activation of the beta2-adrenoceptor and cannabinoid
      CB2 receptors can inhibit sensory nerves and prevent cough. It is currently
      thought that activation of the beta2-adrenoceptor causes c-AMP dependent
      activation of PKA; however, recent research has suggested that the pathway
      involves PKG-mediated opening of the BKCa channel leading to hyperpolarization.

PMID- 21727027
TI  - Endectocides for malaria control.
AB  - Systemic endectocidal drugs, used to control nematodes in humans and other
      vertebrates, can be toxic to Anopheles spp. mosquitoes when they take a blood
      meal from a host that has recently received one of these drugs. Recent laboratory
      and field studies have highlighted the potential of ivermectin to control malaria
      parasite transmission if this drug is distributed strategically and more often.
      There are important theoretical benefits to this strategy, as well as caveats. A
      better understanding of drug effects against vectors and malaria ecologies are
      needed. In the near future, ivermectin and other endectocides could serve as
      potent and novel malaria transmission control tools that are directly linked to
      the control of neglected tropical diseases in the same communities.

PMID- 21727028
TI  - Risk factors for adverse events during collection of peripheral blood stem cells.
AB  - We retrospectively reviewed peripheral blood stem cell (PBSCs) collections
      following 528 mobilization cycles over a 10-year period. A total of 206 (13.1%)
      AEs occurred in association with the 1572 procedures. One hundred and ninety-one
      (12.15%) of the AEs were classified as clinical AEs and 15 (0.95%) were
      classified as apheresis instrument related AEs. The most common clinical AE was
      numbness of the lips, tongue, or extremities (161 procedures, 10.2%) related to
      the infusion of acid citrate dextrose-A (ACD). Multivariate analysis revealed
      high amounts of ACD/weight (odds ratio [OR]=1.11, p=0.009), high numbers of
      procedures (OR=1.33, p<0.001) and female gender (OR=2.83, p<0.001) as being
      significantly associated with clinical AEs. Female gender was shown to be the
      most important risk factor for clinical AEs. Females who have a significantly
      increased risk of AEs would benefit from prophylactic calcium before and/or
      during PBSC collection.

PMID- 21727029
TI  - Use of cytarabine and idarubicin in a newly diagnosed AML patient with a severe
      wound.
AB  - Acute myeloid leukemia (AML) is malignant tumor of haemopoietic precursor cells
      of non-lymphoid lineage. AML can atypically present with non-spesific cutaneous
      lesions or wounds. There are rare acute leukemia cases which present with genital
      ulcerations or pyoderma gangrenosum in the literature. The effect of acute
      leukemia on wound healing is not known, but it is thought that cytopenias and
      chemotherapy can impair wound healing in patients with leukemia. The effects of
      chemotherapeutic agents on wound healing are arguable. Here we present wound care
      strategies and simultaneously applied chemotherapy in an AML patient.

PMID- 21727030
TI  - Successful management of urethro-ileal pouch fistula by cynoacrylate glue
      instillation.
AB  - Uro-enteric fistulae are difficult clinical conditions that have a significant
      bearing on the patient's quality of life. Surgical correction, though
      challenging, is the usual mode of treatment offered to these patients. We
      describe a case of urethro-ileal pouch fistula which could be managed
      successfully without surgery with the help of cynoacrylate glue instillation.

PMID- 21727031
TI  - Behavior problems in children at time of first recognized seizure and changes
      over the following 3 years.
AB  - OBJECTIVES: The purposes of this 36-month study of children with first recognized
      seizures were: (1) to describe baseline differences in behavior problems between
      children with and without prior unrecognized seizures; (2) to identify
      differences over time in behavior problems between children with seizures and
      their healthy siblings; (3) to identify the proportions of children with seizures
      and healthy siblings who were consistently at risk for behavior problems for 36
      months; and (4) to identify risk factors for behavior problems 36 months
      following the first recognized seizure. Risk factors explored included
      demographic (child age and gender, caregiver education), neuropsychological (IQ,
      processing speed), seizure (epileptic syndrome, use of antiepileptic drug,
      seizure recurrence), and family (family mastery, satisfaction with family
      relationships, parent response) variables. METHODS: Participants were 300
      children aged 6 through 14 years with a first recognized seizure and 196 healthy
      siblings. Data were collected from medical records, structured interviews, self
      report questionnaires, and neuropsychological testing. Behavior problems were
      measured using the Child Behavior Checklist and the Teacher's Report Form. Data
      analyses included descriptive statistics and linear mixed models. RESULTS:
      Children with prior unrecognized seizures were at higher risk for behavior
      problems at baseline. As a group, children with seizures showed a steady
      reduction in behavior problems over time. Children with seizures were found to
      have significantly more behavior problems than their siblings over time, and
      significantly more children with seizures (11.3%) than siblings (4.6%) had
      consistent behavior problems over time. Key risk factors for child behavior
      problems based on both caregivers and teachers were: less caregiver education,
      slower initial processing speed, slowing of processing speed over the first 36
      months, and a number of family variables including lower levels of family mastery
      or child satisfaction with family relationships, lower parent support of the
      child's autonomy, and lower parent confidence in their ability to discipline
      their child. CONCLUSIONS: Children with new-onset seizures who are otherwise
      developing normally have higher rates of behavior problems than their healthy
      siblings; however, behavior problems are not consistently in the at-risk range in
      most children during the first 3 years after seizure onset. When children show
      behavior problems, family variables that might be targeted include family
      mastery, parent support of child autonomy, and parents' confidence in their
      ability to handle their children's behavior.

PMID- 21727032
TI  - Four-year results using balloon-based brachytherapy to deliver accelerated
      partial breast irradiation with a 2-day dose fractionation schedule.
AB  - PURPOSE: We present 4-year results from a Phase I/II trial using balloon-based
      brachytherapy to deliver accelerated partial breast irradiation in 2 days.
      MATERIALS/METHODS: Forty-five patients received breast-conserving surgery
      followed by adjuvant radiation therapy using a balloon-based brachytherapy
      applicator delivering 2800 cGy in four fractions over 2 days. Outcomes analyzed
      include toxicities scored using the NCI Common Toxicity Criteria v3.0 scale,
      ipsilateral breast tumor recurrence, regional nodal failure, distant metastasis,
      disease-free survival, cause-specific survival, and overall survival. RESULTS:
      Median age was 66 years (range, 48-83 years) and median tumor size was 0.6 cm
      (range, 0.2-2.3 cm). Five percent of patients were node positive (n=2), whereas
      73% was estrogen receptor positive (n=33). Median followup was 3.7 years (2.4-7.0
      years) with greater than 2 years of followup for all patients. Only Grades 1 and
      2 chronic toxicities were noted with fat necrosis (18%) and asymptomatic seromas
      (42%) being the most common toxicities. Seven percent of patients developed
      ipsilateral rib fractures (n=3), although this was not statistically associated
      with maximum rib dose (p=0.31). Ninety-eight percent of patients had a good or
      excellent radiation-related cosmetic outcome at the time of last followup. There
      were no ipsilateral breast tumor recurrences or regional nodal failures; however,
      2 patients developed distant metastases. Four-year actuarial disease-free
      survival, cause-specific survival, and overall survival were 96%, 100%, and 93%,
      respectively. CONCLUSIONS: Treatment of early-stage breast cancer patients with
      breast-conserving therapy using a 2-day radiation dose schedule resulted in
      acceptable chronic toxicity and similar clinical outcomes as standard 5-day
      fractionation.

PMID- 21727033
TI  - Biochemical and clinical experience with real-time intraoperatively planned
      permanent prostate brachytherapy.
AB  - PURPOSE: To evaluate patient characteristics and dosimetric parameters that
      predict biochemical failure (BCF) after real-time planned low-dose-rate prostate
      brachytherapy. METHODS: From 1998 to 2008, a low-risk cohort by National
      Comprehensive Cancer Network criteria of 341 men with a median followup of 41.6
      months was analyzed. This cohort had a median age of 65.1 years, prostate volume
      of 35.8cc, and pretreatment prostate-specific antigen of 5.6ng/mL. Patients had
      predominately Gleason 6 (95.9%) and T1c (81.3%) disease. About 3.6% of the
      patients received androgen deprivation therapy. Kaplan-Meier and Cox proportional
      hazards survival analysis methods were used to analyze predictors of BCF (Phoenix
      definition). RESULTS: At 72 months, freedom from BCF was 91.1% (95% confidence
      interval=85.0-94.8). The median D(90) was 145.9Gy, and the median V(100) was
      90.3%. Because of infrequent BCF, the following prostate volume groups were
      examined: 15-<25, 25-<35, 35-<45, and 45+cc. Of all possible predictors, only
      small prostate volume (15-<25cc group) was significantly associated with BCF
      (hazard ratio=8.44, 95% confidence interval=1.82-39.14, p=0.007). Using Kaplan
      Meier analysis, time to BCF was also significantly increased in the lowest
      prostate volume 15-<25cc group with 24.1% failing at 48 months compared with 1.6
      5.1% among the other groups. CONCLUSIONS: Real-time planned low-dose-rate
      prostate brachytherapy provides excellent biochemical control as a single-agent
      treatment for low-risk prostate cancer with 91.1% freedom from BCF at 72 months.
      Only prostate volume less than 25cc was an independent predictor of BCF.

PMID- 21727034
TI  - Work environment and recent suicidal thoughts among male university hospital
      physicians in Sweden and Italy: the health and organization among university
      hospital physicians in Europe (HOUPE) study.
AB  - BACKGROUND: Male and female physicians are at elevated suicide risk. The work
      environment has become a focus of attention as a possible contributor to this
      risk. The potential association between work environment and suicidal thoughts
      has been examined among female physicians in several countries, and significant
      findings have been reported. OBJECTIVE: The purpose of this study was to examine
      the role of the work environment in relation to suicidal thoughts among male
      university hospital physicians in 2 European countries. METHODS: Cross-sectional
      multivariate analysis was performed to identify significant associations between
      work-related factors and suicide risk among male physicians from the Health and
      Organization among University Hospital Physicians in Europe (HOUPE) study. The
      dependent variable was termed recent suicidal thoughts, which includes having
      thought about suicide and/or having thought about specific ways to commit suicide
      within the previous year. Adjusted odds ratios (ORs) and CIs are reported.
      RESULTS: Of the 456 Swedish (56%) and 241 Italian (39%) male physicians who
      participated, 12% of the physicians from each country reported affirmatively
      regarding recent suicidal thoughts. Degrading work experiences were associated
      with recent suicidal thoughts for the Swedish and Italian physicians (OR = 2.1;
      95% CI, 1.01-4.5; OR = 3.3; 95% CI, 1.3-8.0, respectively). Role conflict was
      associated with recent suicidal thoughts among the Swedish physicians (OR = 1.6;
      95% CI, 1.1-2.2). Support at work when difficulties arose appeared to be
      protective for the Swedish physicians (OR = 0.7; 95% CI, 0.5-0.96). Italian
      physicians with little control over working conditions had an increased risk of
      recent suicidal thoughts, whereas confidential discussions about work experiences
      appeared to be protective (OR = 0.6; 95% CI, 0.4-0.9). CONCLUSION: Attention
      should be paid to the work environment as it relates to suicide risk among male
      university hospital physicians, particularly to bolstering social support and
      preventing harassment.

PMID- 21727035
TI  - DNA repair and replication influence the number of mutations per adduct of
      polycyclic aromatic hydrocarbons in mammalian cells.
AB  - Polycyclic aromatic hydrocarbons (PAH) are an important class of environmental
      contaminants many of which require metabolic activation to DNA-reactive bay or
      fjord region diolepoxides (DE) in order to exert their mutagenic and carcinogenic
      effects. In this study, the mutagenicity of the bay region diolepoxides (+)-anti
      7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and (+/-)-anti
      1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrodibenzo[a,h]anthracene (DBADE) and the
      fjord region diolepoxides (+/-)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14
      tetrahydrodibenzo[a,l]-pyrene (DBPDE) and (+/-)-anti-3,4-dihydroxy-1,2-epoxy
      1,2,3,4-tetrahydrobenzo[c]-phenanthrene (BPhDE) was compared in nucleotide
      excision repair (NER) proficient and deficient hamster cell lines. The (32)P
      postlabelling assay was applied to analyze DNA adduct levels and the Hprt gene
      mutation assay for monitoring mutations. Previously, we found that the
      mutagenicity per adduct was four times higher for DBPDE compared to BPDE in NER
      proficient cells. In these same cells, the mutagenicity of DBADE and BPhDE
      adducts was now found to be significantly lower compared to that of BPDE. In NER
      deficient cells the highest mutagenicity per adduct was found for BPDE and there
      was a tenfold and fivefold difference when comparing the BPDE data with the DBADE
      and BPhDE data, respectively. In order to investigate to what extent the
      mutagenicity of the different adducts in NER proficient cells was influenced by
      repair or replication bypass, we measured the overall NER incision rate, the rate
      of adduct removal, the rate of replication bypass and the frequency of induced
      recombination in the Hprt gene. Since NER turned out to be an important pathway
      for the yield of mutations, we further analyzed the role of transcription coupled
      NER versus global genome NER. However, our data demonstrate that neither of these
      pathways seems to be the sole factor determining the mutation frequency of the
      four PAH-DE and that the differences in the repair efficiency of these compounds
      could not be related to the presence of a bay or fjord region in the parent PAH.

PMID- 21727037
TI  - The simple and sensitive measurement of malondialdehyde in selected specimens of
      biological origin and some feed by reversed phase high performance liquid
      chromatography.
AB  - A method for the determination of malondialdehyde (MDA) concentrations in
      specimens of animal tissues and feed has been developed using high performance
      liquid chromatography. The MDA concentration in acidified urine samples was
      determined after its conversion with 2,4-dinitrophenylhydrazine (DNPH) to a
      hydrazone (MDA-DNPH). Samples of blood plasma, muscle, liver and feed were
      prepared by saponification followed by derivatisation with DNPH to MDA-DNPH. The
      MDA concentration in chicken and hen feed samples was analysed after
      saponification and derivatisation followed by extractions with hexane. The free
      MDA in plasma samples was determined after deproteinization followed by
      derivatisation of MDA with DNPH. The chromatographic separation of MDA-DNPH
      samples was conducted using Phenomenex C(18)-columns (Synergi 2.5 MUm, Hydro-RP,
      100 A, the length of 100mm) with an inner diameter of 2 or 3mm. MDA in processed
      biological samples was analysed using a linear gradient of acetonitrile in water,
      and the photodiode detector was set to 307 or 303 nm for detection. The current
      method that was utilised was based on the high-efficient derivatisation of MDA
      and was more sensitive compared to previously used methods. The selective and
      sensitive photodetection of the column effluent was found to be suitable for the
      routine analysis of MDA in urine, plasma, muscles and liver of animals and some
      feed samples. Because urine or blood plasma samples can be derivatised in a
      simple manner, the proposed method can also be suitable for the routine, non
      invasive evaluation of oxidative stress in animals and humans.

PMID- 21727036
TI  - Incidence and persistence of 8-oxo-7,8-dihydroguanine within a hairpin
      intermediate exacerbates a toxic oxidation cycle associated with trinucleotide
      repeat expansion.
AB  - The repair protein 8-oxo-7,8-dihydroguanine glycosylase (OGG1) initiates base
      excision repair (BER) in mammalian cells by removing the oxidized base 8-oxo-7,8
      dihydroguanine (8-oxoG) from DNA. Interestingly, OGG1 has been implicated in
      somatic expansion of the trinucleotide repeat (TNR) sequence CAG/CTG.
      Furthermore, a 'toxic oxidation cycle' has been proposed for age-dependent
      expansion in somatic cells. In this cycle, duplex TNR DNA is (1) oxidized by
      endogenous species; (2) BER is initiated by OGG1 and the DNA is further processed
      by AP endonuclease 1 (APE1); (3) a stem-loop hairpin forms during strand
      displacement synthesis by polymerase beta (pol beta); (4) the hairpin is ligated
      and (5) incorporated into duplex DNA to generate an expanded CAG/CTG region. This
      expanded region is again subject to oxidation and the cycle continues. We
      reported previously that the hairpin adopted by TNR repeats contains a hot spot
      for oxidation. This finding prompted us to examine the possibility that the
      generation of a hairpin during a BER event exacerbates the toxic oxidation cycle
      due to accumulation of damage. Therefore, in this work we used mixed-sequence and
      TNR substrates containing a site-specific 8-oxoG lesion to define the kinetic
      parameters of human OGG1 (hOGG1) activity on duplex and hairpin substrates. We
      report that hOGG1 activity on TNR duplexes is indistinguishable from a mixed
      sequence control. Thus, BER is initiated on TNR sequences as readily as non
      repetitive DNA in order to start the toxic oxidation cycle. However, we find that
      for hairpin substrates hOGG1 has reduced affinity and excises 8-oxoG at a
      significantly slower rate as compared to duplexes. Therefore, 8-oxoG is expected
      to accumulate in the hairpin intermediate. This damage-containing hairpin can
      then be incorporated into duplex, resulting in an expanded TNR tract that now
      contains an oxidative lesion. Thus, the cycle restarts and the DNA can
      incrementally expand.

PMID- 21727038
TI  - Characterization of odor-active compounds of various cherry wines by gas
      chromatography-mass spectrometry, gas chromatography-olfactometry and their
      correlation with sensory attributes.
AB  - To characterize the aroma of cherry wine, five samples were analyzed by
      quantitative descriptive sensory analysis, gas chromatography-mass spectrometry
      (GC-MS) and gas chromatography-olfactometry (GC-O). The aroma of cherry wines was
      described by 6 sensory terms as fruity, sour, woody, fermentation, cameral and
      floral. Fifty-one odor-active (OA) compounds were detected by GC-O and quantified
      by GC-MS, and 45 of them were identified. Twenty-nine OA compounds having more
      than 50% detection frequency were selected as specific compounds correlated to
      sensory attributes by partial least squares regression (PLSR). The correlation
      result showed ethyl 2-methyl propionate, 2,3-butanedione, ethyl butyrate, ethyl
      pentanoate, 3-methyl-1-butanol, ethyl hexanoate, 3-hydroxy-2-butanone, ethyl
      lactate, 1-hexanol, (Z)-3-hexen-1-ol, ethyl hydroxyacetate, acetic acid,
      furfural, 2-ethyl-1-hexanol, benzaldehyde, propanoic acid, butanoic acid,
      guaiacol, beta-citronellol, hexanoic acid, 2-methoxy-4-methylphenol, 2-ethyl-3
      hydroxy-4H-pyran-4-one, ethyl cinnamate, 2-methoxy-4-vinylphenol were typical OA
      compounds, which covaried with characteristic aroma of cherry wines.

PMID- 21727039
TI  - Gas chromatography-negative ion chemical ionisation mass spectrometry using o
      (pentafluorobenzyloxycarbonyl)-2,3,4,5-tetrafluorobenzoyl derivatives for the
      quantitative determination of methylphenidate in human plasma.
AB  - A novel electrophoric derivatisation procedure using o
      (pentafluorobenzyloxycarbonyl)-2,3,4,5-tetrafluorobenzoyl chloride for the
      quantitative determination of methylphenidate in human plasma is described. The
      drug can be quantitatively measured down to 0.006 pg/mL plasma due to the
      extraordinary sensitivity of the derivatives under negative ion chemical
      ionisation mass spectrometry. Plasma samples were made alkaline with carbonate
      buffer and treated with extraction solvent (n-hexane) and reagent solution for 15
      min, which, after concentration was measured by GC-NICI-MS. The method is rapid
      as extraction and derivatisation occur in one single step. A stable isotope
      labelled internal standard was used. Validation data are given to demonstrate the
      usefulness of the assay, including selectivity, linearity, accuracy and
      precision, autosampler stability, aliquot analysis, robustness, and prospective
      analytical batch size accuracy. The method has been successfully applied to
      pharmacokinetic profiling of the drug after oral administration.

PMID- 21727040
TI  - Direct injection of human serum and pharmaceutical formulations for glucosamine
      determination by CE-C(4)D method.
AB  - A simple CE-C(4)D method has been developed for the determination of glucosamine
      by direct injection of human serum and pharmaceutical samples. Glucosamine was
      electrokinetically injected and analysed in its protonated form using 20mM
      MES/His (pH 6) as background electrolyte in order to separate it from the matrix
      and to provide a better response to the C(4)D detector. Separation of glucosamine
      in human serum and pharmaceutical samples was performed in 3 min without the need
      for protein precipitation or matrix removal. Good precision in terms of %RSD for
      the migration time and peak area were less than 1.91% (n = 10). The conductivity
      signal was linear with glucosamine concentration in the range 0.10-2.50mg/mL,
      with a detection limit of 0.03 mg/mL. Recoveries of glucosamine in serum and
      pharmaceutical samples were 86.5-104.78%. The method was successfully applied for
      the determination of the glucosamine content in pharmaceutical formulations and
      validated with high performance liquid chromatography (HPLC). Good agreements
      were observed between the developed method, label values and the HPLC method.
      Glucosamine could be detected in spiked serum sample by direct injection. This
      was not possible by HPLC due to co-eluting interferences.

PMID- 21727041
TI  - Simultaneous determination of 3,3',4',5,7-pentamethylquercetin and its possible
      metabolite 3,3',4',7-tetramethylquercetin in dog plasma by liquid chromatography
      tandem mass spectrometry and its application to preclinical pharmacokinetic
      study.
AB  - A sensitive, simple and rapid ultra fast liquid chromatography (UFLC)-ESI-MS/MS
      method was established for the simultaneous determination of 3,3',4',5,7
      pentamethylquercetin (PMQ) and its possible metabolite 3,3',4',7
      tetramethylquercetin (TMQ) in dog plasma using 4',5,7-trimethylapigenin (TMA) as
      the internal standard. The plasma sample was pretreated with acetonitrile for
      protein precipitation and the analytes were separated on an Ultimate XB-CN column
      (5 MUm, 2.1 mm * 150 mm) with the mobile phase consisting of acetonitrile and
      water (2:1, v/v). Detection was performed on a triple-quadrupole tandem mass
      spectrometer under a positive multiple reaction-monitoring mode (MRM). The mass
      transition ion-pair was followed as m/z 373.1-312.1 for PMQ, 359.1-344.0 for TMQ
      and 313.1-298.1 for TMA. The validated concentration ranged from 1.272 to 3060
      ng/mL for PMQ and from 10.35 to 1725 ng/mL for TMQ. The lower limit of
      quantifications for PMQ and TMQ were 1.272 ng/mL and 10.35 ng/mL, respectively.
      The developed-method was successfully applied for the pharmacokinetic study of
      PMQ and its metabolite TMQ in dogs following a single oral dose.

PMID- 21727042
TI  - Determination of uremic solutes in biological fluids of chronic kidney disease
      patients by HPLC assay.
AB  - During chronic kidney disease (CKD), solutes called uremic solutes, accumulate in
      blood and tissues of patients. We developed an HPLC method for the simultaneous
      determination of several uremic solutes of clinical interest in biological
      fluids: phenol (Pol), indole-3-acetic acid (3-IAA), p-cresol (p-C), indoxyl
      sulfate (3-INDS) and p-cresol sulfate (p-CS). These solutes were separated by ion
      pairing HPLC using an isocratic flow and quantified with a fluorescence
      detection. The mean serum concentrations of 3-IAA, 3-INDS and p-CS were 2.12,
      1.03 and 13.03 MUM respectively in healthy subjects, 3.21, 17.45 and 73.47 MUM in
      non hemodialyzed stage 3-5 CKD patients and 5.9, 81.04 and 120.54 MUM in
      hemodialyzed patients (stage 5D). We found no Pol and no p-C in any population.
      The limits of quantification for 3-IAA, 3-INDS, and p-CS were 0.83, 0.72, and 3.2
      MUM respectively. The within-day CVs were between 1.23 and 3.12% for 3-IAA, 0.98
      and 2% for 3-INDS, and 1.25 and 3.01% for p-CS. The between-day CVs were between
      1.78 and 5.48% for 3-IAA, 1.45 and 4.54% for 3-INDS, and 1.19 and 6.36% for p-CS.
      This HPLC method permits the simultaneous and quick quantification of several
      uremic solutes for daily analysis of large numbers of samples.

PMID- 21727043
TI  - Development and validation of a selective and sensitive LC-MS/MS method for
      determination of cycloserine in human plasma: application to bioequivalence
      study.
AB  - A selective and sensitive liquid chromatography-tandem mass spectrometry (LC
      MS/MS) assay for the determination of cycloserine in human plasma is developed
      using niacin as internal standard (IS). The analyte and IS were extracted from
      500 MUL of human plasma via solid phase extraction on Waters Oasis MCX
      cartridges. Chromatographic separation was achieved on a Peerless Basic C18 (100
      mm * 4.6mm, 3 MUm) column under isocratic conditions. Detection of analyte and IS
      was done by tandem mass spectrometry, operating in positive ion and multiple
      reaction monitoring (MRM) acquisition mode. The protonated precursor to product
      ion transitions monitored for cycloserine and niacin were at m/z 103.1 -> 75.0
      and 124.1 -> 80.1 respectively. The method was fully validated for its
      selectivity, interference check, sensitivity, carryover check, linearity,
      precision and accuracy, reinjection reproducibility, recovery, matrix effect, ion
      suppression/enhancement, stability and dilution integrity. The limit of detection
      (LOD) and lower limit of quantitation of the method were 0.0013 and 0.20 MUg/mL
      respectively with a linear dynamic range of 0.20-30.00 MUg/mL for cycloserine.
      The intra-batch and inter-batch precision (%CV) across six quality control levels
      was less than 8.0% for cycloserine. The method was successfully applied to a
      bioequivalence study of 250 mg cycloserine capsule formulation in 24 healthy
      Indian male subjects under fasting condition.

PMID- 21727044
TI  - An ultra-high sensitive bioanalytical method for plasma melatonin by liquid
      chromatography-tandem mass spectrometry using water as calibration matrix.
AB  - For the endogenous substances with an ultra-low level in biological fluids, such
      as melatonin, the blank biological matrix is obviously not "blank". This problem
      leads to a serious issue of the bioanalytical methods development and validation
      by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). This
      work developed and validated an ultra-high sensitive bioanalytical method for
      plasma melatonin by LC-MS/MS using water as calibration matrix. The lower limit
      of quantitation of the method was verified to be 1.0 pg/mL and the method
      exhibited a linear range of 1-5000 pg/mL. Potential matrix effects, accuracy and
      precision were fully monitored and validated by two complementary quality control
      approaches respectively using water and the pooled plasma as matrix. The intra
      run and inter-run precisions were less than 11.5% and 12.2%, respectively, and
      the relative error was below +/- 13.8% for all of 5 quality control levels. The
      method was successfully applied to investigate the daytime (8:00 AM-8:00 PM)
      baseline level of endogenous plasma melatonin, as well as the pharmacokinetic
      profiles of exogenous melatonin after oral administration in beagle dogs.

PMID- 21727045
TI  - Determination of unbound ticagrelor and its active metabolite (AR-C124910XX) in
      human plasma by equilibrium dialysis and LC-MS/MS.
AB  - Ticagrelor is the first direct acting reversibly binding oral platelet P2Y(12)
      receptor antagonist. The parent molecule and the main metabolite (AR-C124910XX)
      are both able to block adenosine diphosphate-induced receptor signaling with
      similar potency. Drug binding to plasma proteins reduces free drug available for
      pharmacologic activity. Therefore, assessing unbound drug is important for
      interpretation of pharmacokinetic/pharmacodynamic findings. This paper describes
      the development and validation of an equilibrium dialysis/LC-MS/MS method for
      measuring unbound ticagrelor and AR-C124910XX in human plasma. Plasma samples
      (200MUl) were dialysed against phosphate buffered saline (37  degrees C, 24h) in
      96-well dialysis plates to separate unbound analytes. Drug-protein binding
      alterations during dialysis were minimized by maintaining physiologic conditions
      (pH 7.4, 37  degrees C). Ticagrelor and AR-C124910XX were quantified in
      dialysates (unbound fraction), retentates and plasma (total concentration) using
      liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) methods.
      Calibration curves were established for the retentate and plasma (total
      concentration) in the ranges 5-5000 ng/ml (ticagrelor) and 2.5-2500 ng/ml (AR
      C124910XX), and for the dialysate in the range 0.25-100 ng/ml (both analytes).
      Both ticagrelor and AR-C124910XX were highly protein bound (>99.8%), i.e. unbound
      fraction <0.2%. Yet, the methodology was successfully applied to determine
      unbound concentrations of ticagrelor and AR-C124910XX in clinical samples.

PMID- 21727046
TI  - Separation of fingerprint constituents using magnetic silica nanoparticles and
      direct on-particle SALDI-TOF-mass spectrometry.
AB  - Two types of amorphous, silica nanoparticles have been produced and used as
      surface assisting agents during laser desorption/ionisation time-of flight-mass
      spectrometry (SALDI-TOF-MS). The first is hydrophilic possessing surface
      aminopropyl groups and the second hydrophobic containing surface phenyl groups.
      Each particle type acts as a solid phase adsorbent, adsorbing analytes according
      to their charge and hydrophobicity. The adsorbed analytes can be directly
      analysed on the particles using SALDI-TOF-MS. Intrinsically magnetisable versions
      of the hydrophobic particles act as magnetic solid phase extraction (MSPE)
      materials which are used to selectively adsorb analytes within a mixture
      deposited onto a surface, transfer the adsorbed components using a magnetic wand
      and to deposit the particles at a site adjacent to that of the original mixture.
      Non-adsorbed components remain at the original site. The extracted and residual
      analytes are then directly analysed on the surface by SALDI-TOF-MS. Using
      fingerprints as an example of a complex biological matrix, this new approach has
      been used to separate polar (amino acids) and non-polar constituents (squalene
      and fatty acids) within latent fingerprints deposited on a surface and for their
      subsequent direct analysis on the surface by SALDI-TOF-MS. Alanine, ornithine,
      lysine and aspartic acid which were undetected or poorly detected prior to
      separation showed improved signal detection after separation.

PMID- 21727047
TI  - Separation of lysozyme using superparamagnetic carboxymethyl chitosan
      nanoparticles.
AB  - Functionalized Fe(3)O(4) nanoparticles conjugated with polyethylene glycol (PEG)
      and carboxymethyl chitosan (CM-CTS) were developed and used as a novel magnetic
      absorbing carrier for the separation and purification of lysozyme from the
      aqueous solution and chicken egg white, respectively. The morphology of magnetic
      CM-CTS nanoparticles was observed by transmission electron microscope (TEM). It
      was found that the diameter of superparamagnetic carboxymethyl chitosan
      nanoparticles (Fe(3)O(4) (PEG+CM-CTS)) was about 15 nm, and could easily
      aggregate by a magnet when suspending in the aqueous solution. The adsorption
      capacity of lysozyme onto the superparamagnetic Fe(3)O(4) (PEG+CM-CTS)
      nanoparticles was determined by changing the medium pH, temperature, ionic
      strength and the concentration of lysozyme. The maximum adsorption loading
      reached 256.4 mg/g. Due to the small diameter, the adsorption equilibrium of
      lysozyme onto the nanoparticles reached very quickly within 20 min. The
      adsorption equilibrium of lysozyme onto the superparamagnetic nanoparticles
      fitted well with the Langmuir model. The nanoparticles were stable when subjected
      to six repeated adsorption-elution cycles. Separation and purification were
      monitored by determining the lysozyme activity using Micrococcus lysodeikticus as
      substrate. The lysozyme was purified from chicken egg white in a single step had
      higher purity, as determined by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). Considering that the superparamagnetic nanoparticles
      possess the advantages of high efficiency, cost-effectiveness and excellent
      binding of a larger amount of lysozyme and easier separation from the reaction
      system, thus this type of superparamagnetic nanoparticles would bring advantages
      to the conventional separation techniques of lysozyme from chicken egg white.

PMID- 21727048
TI  - HPLC determination of fumonisin mycotoxins in maize: a comparative study of
      naphthalene-2,3-dicarboxaldehyde and o-phthaldialdehyde derivatization reagents
      for fluorescence and diode array detection.
AB  - Fumonisins are mycotoxins produced by various species of Fusarium and occur
      naturally in contaminated maize and maize-based foods. Ingestion of fumonisins
      has considerable health implications for humans and animals. Since fumonisins
      lack a useful chromophore or fluorophore, their determination in maize is
      routinely achieved via HPLC with fluorescence detection (FLD) after precolumn
      derivatization. This study optimized naphthalene-2,3-dicarboxaldehyde (NDA)
      derivatization of fumonisins in naturally contaminated maize following strong
      anion exchange (SAX) solid phase extraction (SPE) clean-up and utilizing diode
      array detection (DAD) as a practical alternative simultaneously to FLD. The limit
      of detection (LOD) for fumonisin B(1) (FB(1)), fumonisin B(2) (FB(2)) and
      fumonisin B(3) (FB(3)) with FLD was 0.11 ng, 0.50 ng and 0.27 ng, respectively,
      and with DAD it was 13.8 ng, 12.5 ng and 6.6 ng, respectively injected on column.
      The coefficient of variation (CV, n = 6) for FB(1), FB(2) and FB(3) in a
      naturally contaminated samples obtained with FLD was 2.6%, 1.8% and 5.3%,
      respectively, compared to 6.0%, 3.4% and 9.5%, respectively, obtained with DAD.
      Subsequently the optimized NDA derivatization was compared to the widely used o
      phthaldialdehyde (OPA) derivatization agent as well as alternative sample clean
      up with immunoaffinity column (IAC) by analyzing naturally contaminated maize
      samples (n = 15) ranging in total fumonisin (TFB = FB(1)+FB(2)+FB(3)) levels from
      106 to 6000 MUg/kg. After immunoaffinity column clean-up of extracted samples,
      the recoveries of spiked maize samples for NDA-FLD of FB(1), FB(2) and FB(3) were
      62%, 94% and 64%, respectively. NDA proved to be an effective derivatization
      reagent of fumonisin in naturally contaminated maize samples following IAC clean
      up, except for DAD at TFB levels below 1000 MUg/kg. In contrast NDA
      derivatization following SAX clean-up produced results comparable to OPA only for
      levels below 1000 MUg/kg. Aside from the difference in detection limits, FLD and
      DAD produced comparable results irrespective of the clean-up method or the
      derivatization agent.

PMID- 21727049
TI  - Quantification of trimesic acid in liver, spleen and urine by high-performance
      liquid chromatography coupled to a photodiode-array detection.
AB  - The quantification of trimesic acid, a constitutive organic linker from the
      biodegradable porous iron(III) trimesate MIL-100(Fe) (MIL stands for Materials
      from Institut Lavoisier), has been performed in different biological complex
      media (liver, spleen and urine) using a liquid-liquid extraction procedure. A
      recovery exceeding 92 wt% was achieved from rat tissues and urine spiked with
      trimesic acid. After extraction, the determination of the trimesic acid
      concentration was realised by using a simple and accurate high-performance liquid
      chromatography (HPLC) method using photodiode-array detection (PDA) and
      aminosalicylic acid, as internal standard. Linearity of this method was kept from
      0.01 to 100mg of trimesic acid per liter of urine and from 0.05 to 5.00 wt% of
      trimesic acid per tissue weight. The limit of detection of the method was 0.01
      MUg per injection. This method was finally applied to analyze and quantify the
      amount of trimesic acid in rat urine and tissue samples at the different stages
      of degradation of MIL-100(Fe).

PMID- 21727050
TI  - Determination of temozolomide in serum and brain tumor with micellar
      electrokinetic capillary chromatography.
AB  - Micellar electrokinetic capillary chromatographic (MEKC) with photodiode-array
      detection was applied to determine temozolomide (TMZ) in human serum and brain
      tumor. The limit of quantitation (LOQ) was 0.096 MUg/mL using 325 nm as detection
      wavelength. The method made possible that the TMZ could be detected in in vivo
      serum samples without sample pretreatment. In order to detect TMZ at lower
      concentration, an extraction with ethyl acetate was applied to preconcentrate the
      analyte. Small amount of brain tumor tissues (less than 1g) were lyophilized and
      pretreated using extraction as a clean up and concentrating step. After removing
      the organic solvent a final sample volume of only 10 MUL was analyzed. The
      obtained peak concentrations (8.2-10.1 MUg/mL) and T(max) (44-65 min) of TMZ in
      serum were similar to the data reported by others, the in vivo TMZ concentrations
      found in brain tumor ranged between 0.061 and 0.117 MUg/g.

PMID- 21727051
TI  - Therapeutic drug monitoring of tacrolimus by liquid chromatography-tandem mass
      spectrometry: is it truly a routine test?
AB  - Therapeutic drug monitoring of tacrolimus by high-performance liquid
      chromatography-tandem mass spectrometry has become standard practice. We report
      on the long-term (4.5 years) use of one such method. Whole blood samples (25 MUL)
      were treated with zinc sulphate (100 MUL) and acetonitrile containing ascomycin
      (internal standard, 250 MUL). A high-performance liquid chromatography-tandem
      mass spectrometer operating in positive ion mode with an electrospray interface
      was used. Chromatography was performed on a TDM C(18) cartridge column (10 mm *
      2.1 mm, 10 MUm, Waters) using a switch gradient. A total of 4029 batches were
      analyzed for tacrolimus; this comprised of 81950 analyses of which 61027 were
      patient samples. Calibration curves (1.0-50 MUg/L) were run on 1765 occasions
      (mean r(2)=0.999; range r(2)=0.988-0.999). Inter-batch accuracy and imprecision
      of the method (2.5, 12.5 and 30.0 MUg/L), when in routine use, was 97.6-98.5% and
      <8.0%, respectively (n=4031). Evaluation of the method against other methods in
      an external quality control scheme revealed good agreement by linear regression
      analysis (y=0.924x+0.196, r(2)=0.985). The percentage difference between our
      results and that of all methods revealed a mean bias of -6.3% and a range of 
      33.3% to 11.1%. During the evaluation period, four batch failures occurred (0.1%
      failure rate) and greater than 1000 samples per analytical column was achieved.
      In conclusion, the described method is ideally suited as a routine test for
      tacrolimus in the clinical setting.

PMID- 21727052
TI  - Deus ex machina: the use of technology in type 1 diabetes.
AB  - Deus ex machina: in ancient Greek theatre, towards the end of a performance, a
      crane-like device was often used to lower an actor playing a god onto the stage
      in order to solve an apparently intractable problem in a plot-line. Nowadays,
      perceived wisdom believes that difficult clinical scenarios in diabetes can be
      alleviated by the introduction of technologies such as insulin pump therapy and
      glucose sensing. This "God from the Machine" approach to problem solving has been
      enthusiastically embraced by a small number of enthusiasts within the diabetes
      care community but access to these technologies is still very limited in the UK.
      The question is can the use of technology reduce or even eliminate the biological
      and psychological variables that prevent people living with diabetes achieving
      the standard of blood glucose control desired and if so should availability be
      more widespread?

PMID- 21727053
TI  - The Israel DNA database--the establishment of a rapid, semi-automated analysis
      system.
AB  - The Israel Police DNA database, also known as IPDIS (Israel Police DNA Index
      System), has been operating since February 2007. During that time more than
      135,000 reference samples have been uploaded and more than 2000 hits reported. We
      have developed an effective semi-automated system that includes two automated
      punchers, three liquid handler robots and four genetic analyzers. An inhouse LIMS
      program enables full tracking of every sample through the entire process of
      registration, pre-PCR handling, analysis of profiles, uploading to the database,
      hit reports and ultimately storage. The LIMS is also responsible for the future
      tracking of samples and their profiles to be expunged from the database according
      to the Israeli DNA legislation. The database is administered by an in-house
      developed software program, where reference and evidentiary profiles are
      uploaded, stored, searched and matched. The DNA database has proven to be an
      effective investigative tool which has gained the confidence of the Israeli
      public and on which the Israel National Police force has grown to rely.

PMID- 21727054
TI  - Evaluation of three DNA extraction protocols for forensic STR typing after laser
      capture microdissection.
AB  - In forensic sciences, short tandem repeat (STR) analysis is a valuable tool in
      identifying the donor(s) of biological stains. Laser capture microdissection
      (LCM) can be used as a cell separating technique to isolate specific cell types
      in mixed samples. An important challenge lies in the development of a DNA
      isolation method appropriate for laser microdissected cells, as these samples
      usually contain minute amounts of cells. In this study three different DNA
      isolation methods for LCM collected cells were compared. The PicoPure DNA
      extraction method outperformed both other methods (IQTM system and short alkaline
      method). Consequently, the minimal number of LCM collected cells necessary for
      STR typing was determined. Using the PicoPure DNA extraction method, full DNA
      profiles could be obtained from as little as 10 cells. Nevertheless, despite the
      occurrence of allelic drop out in some of the samples, lower amounts of cells
      gave rise to useful DNA profiles.

PMID- 21727055
TI  - Ruptured aneurysm of the inferior thyroid artery, which treatment?

PMID- 21727057
TI  - Mixed neurothekeoma of the upper limb.

PMID- 21727056
TI  - Acute myopathy and acne fulminans triggered by isotretinoin therapy.

PMID- 21727058
TI  - Effects of cyclosporine on pruritus and serum IL-31 levels in patients with
      atopic dermatitis.

PMID- 21727059
TI  - [Node negative breast cancer. Beyond international consensus: a pragmatic
      approach].
AB  - Apart from therapeutic advances related to new treatments, our practices in the
      management of early breast cancer have been modified by to key organizational
      settings (1) mass screening, substantially altering the presentation and
      epidemiology of breast cancer and (2) the development of guidelines to ensure
      that any patient management is in agreement with the demonstrated impact in the
      adjuvant treatment. In daily practice, the impact of screening and guidelines
      recommendations has put us now in a paradoxical situation: while the majority of
      non-metastatic breast cancers treated in the hexagon are node negative, most of
      the results of clinical studies on chemotherapy and targeted therapies today
      arise from populations predominantly node positive. Therefore, it seemed
      legitimate to convene a working group around a reflection on the directions of
      adjuvant chemotherapy in a growing node negative population in order to better
      respond to the questions of the field oncologists, trying to address the
      discrepancies between different existing guidelines.

PMID- 21727060
TI  - Interleukin-1 beta, interleukin-6 and TGF-beta in follicular tissue of impacted
      third molars.
AB  - The clinical evaluation and management of impacted third molars remain
      challenging. The aim of the present study was to investigate possible
      associations between follicular tissue cytokines and radiographic manifestations
      of impacted third molar. The population included 72 patients who underwent
      surgical extraction of impacted third molars. All these patients underwent a
      preliminary panoramic radiograph. Levels of interleukin-1 beta (IL-1beta),
      interleukin-6 (IL-6) and transforming growth factor beta (TGF-beta) in tissue
      extracts were determined using ELISA. There were no significant differences
      between bony and tissue impaction as regards IL-1beta, IL-6 and TGF-beta levels.
      Moreover, the same results were obtained as far as the amount of pericoronal
      space and the presence or absence of a history of pericoronitis are concerned.
      These results suggest that radiographic findings or a history of pericoronitis
      are not associated with levels of expression of pro-inflammatory cytokines in
      patients undergoing surgical removal of impacted third molars. However, further
      studies are needed to address the possibility of variability during disease
      progression.

PMID- 21727061
TI  - Detection of urease-negative Bordetella bronchiseptica from the field.
AB  - Four urease-negative Bordetella bronchiseptica isolates originating from pigs
      were examined by phenotypic and molecular methods. The phenotypic properties of
      the isolates were in harmony with the data of the literature, except for the lack
      of urease activity in conventional tube test, API 20 NE and DiatabsTM assays.
      Using genotypic methods, the urease-negative isolates did not differ from the
      urease-positive reference strain. They were positive in species-specific and ureC
      PCR, and all strains showed uniform bands in PCR-RFLP studies of flaA genes. The
      reason for the lack of urease activity, a characteristic considered species
      specific for B. bronchiseptica, needs to be studied further. The finding
      underlines the significance of genotyping when the phenotypic identification of
      B. bronchiseptica seems questionable.

PMID- 21727062
TI  - Effect of dietary electrolyte balance on production, immune response and mineral
      concentrations of the femur in broilers.
AB  - The aim of this study was to assess the age-related effects of dietary
      electrolyte balance (DEB) on the performance, immune response (from day 0 to 42)
      and macromineral content of femur ash of broilers. The DEB values of the
      purchased commercial broiler diets were modified with the addition of NH4Cl or
      NaHCO3 to formulate the diets (DEB 325, 250, 175, 100, 25 and -50 mmol/kg) for
      this investigation. A total of 396 chickens were divided into 6 treatment groups
      and fed with the experimental diets for 6 weeks. During the first two weeks of
      life, DEB did not influence feed intake and body weight gain; however, by the
      21st day of age DEB 175 and between 22 and 42 days of age DEB 250 mmol/kg gave
      significantly better results than the control. DEB did not affect the
      macromineral concentrations of bone ash. The immune response of broilers on low
      DEB (< 175 mmol/kg) was faster and more intensive than that of chickens on diets
      with medium or high DEB (> 175 mmol/kg). It can be concluded that the optimal DEB
      value required for the best body weight gain is significantly influenced by the
      age of broilers. Our results call attention to the discrepancy between the
      decreasing DEB level of commercial broiler diets and the age-related increase of
      'electrolyte requirements' of broilers. It is also interesting that DEB may
      influence not only the performance but also the immune response of broilers.

PMID- 21727063
TI  - Experimentally induced melanin-like pigmentation (thesaurismosis) related to
      acorn ingestion in Nero Siciliano pigs.
AB  - In this study, an experimental challenge was carried out by feeding Nero
      Siciliano pigs with acorn to evoke melanin-like pigmentation and support the
      hypothesis that it is caused by ingested material. Twelve pigs were studied, 6
      fed with acorns and 6 fed commercial feed. At slaughter, all the animals fed on
      acorns showed black discolouration of almost all lymph nodes. The lymph nodes
      were normal in size and shape. Histochemical tests performed on tissues allowed
      us to identify and differentiate the pigment. Immunohistochemical staining for
      macrophage markers showed macrophages containing a variable amount of melanin
      like granules. Our data, and the well-known steps of melanin formation, confirm
      that swine enzymes could act on phenolic substances found in acorns.

PMID- 21727064
TI  - A case of hepatic carcinoid in a red deer hind (Cervus elaphus).
AB  - A carcinoid tumour in the liver of a red deer hind (Cervus elaphus) is described.
      Macroscopically, the liver was considerably enlarged with multifocal, firm,
      yellow and red nodular neoplastic masses, which were histopathologically
      diagnosed as hepatic carcinoids. The diagnosis was confirmed by modified
      Grimelius staining, which demonstrated numerous small argyrophilic granules in
      the cytoplasm of neoplastic cells, and by immunohistochemistry. The neoplastic
      cells gave a strong positive reaction for neuron-specific enolase (NSE) and
      synaptophysin and a weak positive reaction for chromogranin A. To our knowledge,
      this is the first report of a hepatic carcinoid in red deer.

PMID- 21727065
TI  - Assessment of the cardiotoxicity of tulathromycin in rabbits.
AB  - The aim of this study was to determine the cardiotoxic potency of tulathromycin.
      Tulathromycin (10 mg/kg, SC) was administered to ten adult male rabbits, and
      blood samples were obtained before and after drug administration (0 and 6 hours).
      Serum cardiac damage markers (troponin I, creatine kinase-MB, myoglobin, lactate
      dehydrogenase, aspartate aminotransferase), routine serum biochemical values
      (alkaline phosphatase, alanine aminotransferase, gamma-glutamyltransferase,
      creatinine, blood urea nitrogen, cholesterol, triglyceride, high-density
      lipoprotein, amylase, total protein, albumin, glucose, calcium, ionised calcium,
      sodium, potassium), white blood cell (WBC) and red blood cell (RBC) counts,
      arterial blood gas parameters (pH, partial carbon dioxide pressure, partial
      oxygen pressure, actual bicarbonate, standard bicarbonate, total carbon dioxide,
      base excess in vivo, base excess in vitro, oxygen saturation, packed cell volume,
      haemoglobin) and serum oxidative status (malondialdehyde, nitric oxide,
      superoxide dismutase, retinol, beta-carotene) were measured. Increased levels of
      troponin I, creatine kinase-MB and creatinine, and decreased WBC counts, ionised
      calcium and potassium levels were observed after drug administration.
      Tulathromycin treatment may cause cardiotoxicity, but its effects may be less
      dramatic than those of other macrolide antibiotics frequently used in veterinary
      medicine.

PMID- 21727066
TI  - Effect of cadmium injected in ovo on hatching results and the activity of plasma
      hydrolytic enzymes in newly hatched chicks.
AB  - The aim of the study was to determine the toxicity of cadmium ions in chick
      embryos, using plasma hydrolytic enzyme as its biomarker. Hatching eggs (n = 300)
      from Ross 308 broilers were incubated under standard conditions. On day 4 of
      incubation, 50 MUl of saline solution, containing Cd ions at a concentration from
      0 (control group) to 24 MUg, was injected in ovo into the egg albumen. The
      results indicate that the administration of cadmium at doses exceeding 1 MUg/egg
      caused a gradual decrease in hatchability, with an LD50 of 3.9 MUg/egg. The
      greatest differences between the groups in the enzymatic activities studied were
      found for N-acetyl-beta-D-glucosaminidase (NAG), beta-D-mannosidase (beta-MAN)
      and arylsulphatase (ARYL). Compared to the control group, in the blood serum of
      chicks from the groups receiving 3, 6 and 12 MUg Cd/egg the NAG activity
      increased by 79, 108 and 54% and beta-MAN activity by 33, 119 and 108%,
      respectively. Exposure to cadmium at a dose of 1 to 6 MUg per egg caused an about
      60% increase in ARYL activity while a dose of 12 MUg decreased the activity by
      about 35% below the level observed in the control group. These findings show that
      cadmium has a similar toxicity mechanism in mammals and birds, which opens the
      possibility of using NAG activity as a biomarker of the cytotoxic effect of
      cadmium in birds.

PMID- 21727067
TI  - Relationship between milk somatic cell count and postpartum ovarian cyclicity and
      fertility in dairy cows.
AB  - The main objective of the study was to describe the relationship of high somatic
      cell count (SCC) with the incidence of abnormal postpartum resumption of ovarian
      cyclicity and reproductive performance in dairy cows. The factors influencing SCC
      were also investigated. Four hundred and forty-seven cows from six dairy herds in
      Japan were monitored for SCC and postpartum resumption of ovarian cyclicity. Cows
      with high SCC (200,000 to 500,000) had a higher incidence of prolonged luteal
      phase (P < 0.01) than cows with an SCC of 50,000 to 100,000. The high SCC cows (>
      500,000) also showed a higher incidence of delayed first ovulation post partum
      than cows with an SCC <=500,000 (P < 0.05) during the first month post partum.
      Cows with an SCC of 200,000 to 500,000 showed lower conception and pregnancy
      rates, and more days from calving to conception than cows with an SCC of less
      than 200,000 (P < 0.05). Cows in parity 5 or more had a higher incidence of high
      SCC than cows in the first and second parities (P < 0.05). It is concluded that
      cows with a high SCC have a higher incidence of abnormal postpartum resumption of
      ovarian cyclicity, leading to reduced reproductive performance.

PMID- 21727068
TI  - Artificial reproduction of wild and cultured barbel (Barbus barbus, Cyprinidae)
      under controlled conditions.
AB  - The aim of this work was to compare the effects of controlled reproduction of
      cultured and wild common barbel, Barbus barbus (L.). Preparations containing
      different GnRH analogues and dopamine receptor antagonists (Ovopel, Ovaprim) as
      well as human chorionic gonadotropin (hCG) (in the case of cultured fish) were
      applied and their influence on ovulation, spermiation and quality of gametes
      obtained was determined. No differences in the qualitative or quantitative
      parameters of semen were found between fish stimulated with different hormonal
      preparations and those not receiving hormonal stimulation. The high suitability
      of Ovaprim for ovulation induction in (cultured and wild) barbel was confirmed.
      The highest synchronisation of ovulation was obtained after the application of
      Ovopel (18 +/- 3 h), but the best results of controlled reproduction (expressed
      as the percentage of ovulations and survival of embryos) were obtained by
      applying Ovaprim (83.2 +/- 4.1). A significantly higher percentage of ovulation
      was obtained in cultured fish (80-90%) than in wild fish (< 25%).

PMID- 21727069
TI  - Experimental results of using autologous rectus fascia sheath for venous patch
      grafts in dogs.
AB  - Autologous vascular patch grafts developed from the internal rectus sheath were
      implanted onto the bilateral common iliac vein and jugular vein of 4 experimental
      beagle dogs. During the development and implanting of the grafts no technical
      difficulties or perioperative complications were encountered. The follow-up
      lasted 6 months and 3 months in the case of the common iliac vein grafts and the
      jugular grafts, respectively. In the postoperative period, the morphological and
      functional characteristics of the implanted venous sections were examined by
      Doppler ultrasonography and CT angiography. Normal patency was detected, and none
      of these check-ups showed obturation or stenosis. The histological survey showed
      no mesothelial cell layer, but the insides of the grafts showed total
      restructuring and were covered by a normal endothelial layer. No difference could
      be detected between samples harvested 3 and 6 months after implanting. The
      immunohistochemical examinations using anti-claudin-5 and anti-CD31 antibodies
      confirmed the preliminary results of the histological examinations that the
      luminal surfaces of the implanted grafts developed a differentiated monolayer
      endothelium which was free of degenerative and inflammatory signs. The control
      examinations show the suitability of the internal rectus sheath as a venous wall
      donor.

PMID- 21727070
TI  - Field efficacy of different vaccines against infectious bursal disease in broiler
      flocks.
AB  - A field study was performed to determine the efficacy of three commercially
      available vaccines against infectious bursal disease (IBD) in commercial broilers
      raised in a high IBD virus (IBDV) risk area. Live attenuated intermediate and
      intermediate plus vaccines were used in four flocks. Birds were vaccinated orally
      at the estimated vaccination time. Three broiler flocks were vaccinated
      subcutaneously with a turkey herpesvirus (HVT)-IBD vector vaccine at one day old.
      Evaluation of the efficacy of different vaccines was focused on humoral immune
      response, bursa/body weight (B/Bw) ratio, molecular detection of IBDV in
      ileocaecal tonsils and bursa of Fabricius, and production parameters. The
      serological results showed that although the uptake of all three vaccine strains
      was confirmed in the lymphoid organs, no significant antibody response to
      vaccination was detected in flocks vaccinated with intermediate and intermediate
      plus vaccines. A significant increase in antibody titres detected in flocks
      vaccinated with the vector vaccine indicated its ability to induce an immune
      response in birds with a high level of maternally derived antibodies.
      Observations obtained in this field trial did not confirm the expected reduction
      of the B/Bw ratio in flocks vaccinated with less attenuated vaccines. No
      significant differences were observed between birds vaccinated with the vector
      vaccine and those immunised with the intermediate plus vaccine. Very virulent
      IBDV was confirmed in the flock vaccinated with the intermediate vaccine. The
      infection induced reduced B/Bw and moderate mortality but did not affect the
      production parameters. Field infection was not detected in broilers vaccinated
      with the intermediate plus vaccine and the vector vaccine.

PMID- 21727071
TI  - Serological evidence for BVDV-1 infection in goats in Poland - short
      communication.
AB  - A serological survey was conducted in 2007 in the breeding goat population in
      Poland to gain insights into the epidemiology of pestivirus infection. All
      breeding herds were included in the study and representative serum samples were
      taken in each herd to evaluate herd-level seroprevalence at 10% expected
      individual-level prevalence and 95% level of confidence. Altogether 1060 serum
      samples from 49 herds were tested with blocking ELISA and then the positive and
      inconclusive results were confirmed in a serum neutralisation test, which also
      allowed us to determine the pestivirus species responsible for seroconversion.
      Herd-level seroprevalence proved to be 10.2% and bovine viral diarrhoea virus
      type 1 (BVDV-1) was responsible for the seroconversion in seven out of eight
      cases. In the remaining serum sample the causative virus could not be identified
      due to a pronounced cross-neutralising activity possibly derived from multiple
      infections. This is the first report on the diagnosis of BVDV-1 infection in
      Polish goats.

PMID- 21727072
TI  - Attempts to detect West Nile virus in wild birds in Poland.
AB  - The aim of the study was to attempt the detection of West Nile virus (WNV) in
      wild birds in Poland. Forty-eight species of 1912 wild birds were used for the
      investigations. The birds were derived from various locations in Poland from
      early spring till late autumn of the years 2009-2011. The brain samples were
      homogenised and cellular RNA was isolated. Two methods (RT-PCR and nested RT-PCR)
      were used. The presence of WNV RNA was not detected in the samples examined.
      Additionally, a short analysis of the epizootiological situation regarding the
      presence of WNV in Poland is presented.

PMID- 21727074
TI  - Screening obese students for acanthosis nigricans and other diabetes risk factors
      in the urban school-based health center.
AB  - OBJECTIVE: To determine the prevalence of acanthosis nigricans (AN) and other
      diabetes risk factors in urban school health clinics. METHODS: During the period
      2006-2009 nurse practitioners (NPs) screened students who had a BMI >= 95th
      percentile and 1 additional diabetes risk factor. Blood glucose (BG) was measured
      by finger stick. NPs were trained on how to ascertain the presence of AN on the
      neck area. RESULTS: NPs screened 854 students (mean age 11.4 years, 60.5% female,
      and 73.3% black). AN and elevated BG were found among 26% and 6.4% of students,
      respectively. Females and minorities were respectively 50% and 4 times more
      likely to have AN. Youth with AN were twice as likely to have elevated glucose.
      CONCLUSION: AN can be easily identified by trained health care professionals even
      in busy school-based clinic settings. Checking for AN and appropriate education
      and counseling should become a routine part of electronic documentation in
      overweight youth.

PMID- 21727075
TI  - Thrombocytopenia in a 3-year-old well-appearing child.

PMID- 21727076
TI  - The lived experience of UK street-based sex workers and the health consequences:
      an exploratory study.
AB  - The complex, difficult lives and subsequent health issues of street-based female
      sex workers are well documented. This paper explores the health needs of a group
      of sex workers in one geographical locality in the north-west of England.
      Interviews were conducted with a number of women currently engaged in sex work,
      with the aim of identifying factors maintaining them in this work and examining
      their experience of health and health-related services. A thematic analysis
      revealed considerable life circumstance complexity, with violence, drugs, alcohol
      and housing problems being prevalent factors. The combination of such factors
      compounds the likelihood of the women's social exclusion. Other themes related to
      the casual perception the women had of their own health needs, their generally
      poor experience of services and the demonstrable impact of one specific service
      in supporting a group so reluctant to engage. The study suggests poor
      understanding of the complex needs of street-based sex workers by both services
      and professionals, particularly a failure to engage with the reality of these
      women's lives and the factors that maintain them in this work.

PMID- 21727079
TI  - Importance of ventricular longitudinal function in chronic heart failure.
AB  - AIMS: Despite its immediate relevance, cardiopulmonary exercise testing (CPET) is
      infrequently performed in the presence of chronic heart failure (CHF). Previous
      studies of patients suffering from CHF have found a closer correlation between
      exercise capacity and measurements of diastolic than systolic
      ventricularfunction. We examined the correlation between echocardiographic
      measurements and (i) results of CPET and (ii) cardiovascular prognosis. METHODS
      AND RESULTS: We performed resting two-dimensional echocardiograms and CPET in 140
      patients with CHF (mean age = 61 +/- 13 years, 111 men). The underlying heart
      disease was ischaemic in 48 patients (34%). They were followed for a mean of 38
      months (range 28-52). The mean left ventricular (LV) ejection fraction (EF) was
      30 +/- 9% and peak VO2 17.2 +/- 6.5 mL/kg/min. LVEF correlated weakly with peak
      VO2 (r = 0.21), while systolic and early diastolic LV longitudinal function
      correlated best [early diastolic peak velocity at the mitral annulus (E'): r =
      0.38; global longitudinal strain (GLS): r = -0.4; P <0.001 for both]. By multiple
      variable regression analysis, the best prediction of peak VO2 was derived from a
      model based on age, mitral annulus end-diastolic peak velocity (A'), GLS, right
      ventricular (RV) systolic strain, and left atrial systolic strain (r2 = 0.57; P
      <0.0001). The two best independent predictors of adverse cardiovascular events at
      28 months were GLS (odds ratio 1.31, P <0.001; prognostic cut-off = -8%) and RV
      systolicstrain (odds ratio 1.05, P =0.01; prognostic cut-off = -22%). CONCLUSION:
      Resting RV and LV longitudinal functions were reliable predictors of adverse
      cardiovascular events and correlated moderately with, but not took to the place
      of, CPET measurements.

PMID- 21727078
TI  - Factors contributing to the success of folic acid public health campaigns.
AB  - BACKGROUND: Studies in the 1990s have found that periconceptional dietary folate,
      supplementation of folic acid or supplemental multivitamins containing folic
      acid, help prevent neural tube defect (NTDs) if taken at the right time. This
      literature review assesses the extant folic acid public health campaigns
      literature and identifies some common variables used in folic acid consumption
      campaign evaluations. METHODS: This review was part of a larger study that
      searched PUBMED, PsycINFO and Embase from 1976 to 2010 to identify articles
      related to the psychosocial and economic impact of NTDs (especially spina bifida)
      on patients and caregivers. RESULTS: Awareness of folic acid levels prior to
      conception improved post-campaign from 6 to 41%. Knowledge about consumption and
      correct periconceptional use of folic acid also improved. However, in most
      studies more than 50% of women did not take folic acid as prescribed. Many
      factors were associated with or without taking folic acid post-campaign,
      including incomplete outreach, prior awareness and knowledge, closeness to
      pregnancy, demographics and other personal characteristics. CONCLUSIONS:
      Sustained campaigning to maintain awareness about and promote periconceptional
      consumption of folic acid in order to reduce the incidence of NTDs is clearly
      needed. Additional initiatives could complement existing public health
      strategies.

PMID- 21727080
TI  - Pushed to the limit: consequences of climate change for the Araucariaceae: a
      relictual rain forest family.
AB  - BACKGROUND AND AIMS: Under predicted climate change scenarios, increased
      temperatures are likely to predispose trees to leaf and other tissue damage,
      resulting in plant death and contraction of already narrow distribution ranges in
      many relictual species. The effects of predicted upward temperatures may be
      further exacerbated by changes in rainfall patterns and damage caused by frosts
      on trees that have been insufficiently cold-hardened. The Araucariaceae is a
      relictual family and the seven species found in Australia have limited natural
      distributions characterized by low frost intensity and frequency, and warm summer
      temperatures. The temperature limits for these species were determined in order
      to help understand how such species will fare in a changing climate. METHODS:
      Experiments were conducted using samples from representative trees of the
      Araucariaceae species occurring in Australia, Agathis (A. atropurpurea, A.
      microstachya and A. robusta), Arauacaria (A. bidwilli, A. cunninghamii and A.
      heterophylla) and Wollemia nobilis. Samples were collected from plants grown in a
      common garden environment. Lower and higher temperature limits were determined by
      subjecting detached winter-hardened leaves to temperatures from 0 to -17  degrees
      C and summer-exposed leaves to 25 to 63  degrees C, then measuring the efficiency
      of photosystem II (F(v)/F(m)) and visually rating leaf damage. The exotherm, a
      sharp rise in temperature indicating the point of ice nucleation within the cells
      of the leaf, was measured on detached leaves of winter-hardened and summer
      temperature-exposed leaves. KEY RESULTS: Lower temperature limits (indicated by
      FT(50), the temperature at which PSII efficiency is 50 %, and LT(50) the
      temperature at which 50 % visual leaf damage occurred) were approx. -5.5 to -7.5 
      degrees C for A. atropurpurea, A. microstachya and A. heterophylla, approx. -7 to
      -9  degrees C for A. robusta, A. bidwillii and A. cunninghamii, and -10.5 to -11 
      degrees C for W. nobilis. High temperature damage began at 47.5  degrees C for W.
      nobilis, and occurred in the range 48.5-52  degrees C for A. bidwillii and A.
      cunninghamii, and in the range 50.5-53.5  degrees C for A. robusta, A.
      microstachya and A. heterophylla. Winter-hardened leaves had ice nucleation
      temperatures of -5.5  degrees C or lower, with W. nobilis the lowest at -6.8 
      degrees C. All species had significantly higher ice nucleation temperatures in
      summer, with A. atropurpurea and A. heterophylla forming ice in the leaf at
      temperatures >3  degrees C higher in summer than in winter. Wollemia nobilis had
      lower FT(50) and LT(50) values than its ice nucleation temperature, indicating
      that the species has a degree of ice tolerance. CONCLUSIONS: While lower
      temperature limits in the Australian Araucariaceae are generally unlikely to
      affect their survival in wild populations during normal winters, unseasonal
      frosts may have devastating effects on tree survival. Extreme high temperatures
      are not common in the areas of natural occurrence, but upward temperature shifts,
      in combination with localized radiant heating, may increase the heat experienced
      within a canopy by at least 10  degrees C and impact on tree survival, and may
      contribute to range contraction. Heat stress may explain why many landscape
      plantings of W. nobilis have failed in hotter areas of Australia.

PMID- 21727081
TI  - Factors associated with successful resuscitation of out-of-hospital cardiac
      arrest at Rajavithi Hospital's Narenthorn Emergency Medical Service Center,
      Thailand.
AB  - The objective of this study is to determine factors associated with successful
      resuscitation of out-of-hospital cardiac arrest (OHCA) patients by Narenthorn
      Emergency Medical Service Center (EMS), Thailand. A retrospective observational
      study was conducted with 73 OHCA patients who were resuscitated from December
      2004 to January 2007. Inferential statistics, univariate (chi(2)) and
      multivariate analyses (logistic regression) were applied for data analysis. A
      total of 73 OHCA patients were included. The mean age was 58.3 years; 86.3% were
      >=40 years, 72.6% were male. The causes of arrest were cardiac problem 53.4%. In
      all, 46.6% were witnessed arrest; 53.4% had response time (RT) >=10 minutes, and
      27.4% had bystander cardiopulmonary resuscitation (CPR). Overall, 79.5% were
      found in the residence. Initial electrocardiogram showed that 74% were
      nonshockable rhythm. A total of 34.2% were resuscitated by an EMS team with <4
      members, and 53.4% had return of spontaneous circulation, survival to admission
      was 61.5% and survival to discharge was 7.7%. Witnessed arrest (odds ratio [OR] =
      7.403; 95% confidence interval [CI] = 2.169-24.683) and bystander CPR (OR =
      5.619; 95% CI = 1.014-36.170) had correlation with successful resuscitation of
      OHCA patients. RT showed a trend toward statistical significance (OR = 1.051; 95%
      CI = 0.765-16.083). This study found that witnessed arrest and bystander CPR were
      major factors associated with successful resuscitation of OHCA patients. Our
      findings will be useful for the development of community programs to decrease the
      mortality from OHCA.

PMID- 21727082
TI  - The cost-effectiveness of HIV voluntary counseling and testing in China.
AB  - China has experienced a dramatic increase in the number of HIV infections. To
      control the AIDS epidemic, free HIV voluntary counseling and testing has been
      made available in China. This study compared the cost-effectiveness of this
      program for 2 populations-the general population and men who have sex with men
      (MSM), to examine the value for money of this program. A Bernoulli-process model
      has been used to translate the changes in sexual behaviors to the number of HIV
      infections averted. Costs are estimated from a societal perspective. The outcomes
      are measured in terms of the incremental cost per HIV infection averted and the
      incremental cost per disability-adjusted life-year averted. The study found that
      the voluntary counseling and testing for the general population is not cost
      effective based on the threshold adopted, whereas the same HIV prevention program
      for MSM is cost-saving. These results suggest that the efficiency of resources
      used could be substantially improved by appropriately targeting high-risk
      population groups. Therefore measures should be taken to increase the uptake of
      this intervention among high-risk groups.

PMID- 21727083
TI  - Impact of morbidity and life events on successful aging.
AB  - The purpose of this study was to examine the risks of the incidence of chronic
      conditions and life events on successful aging. Longitudinal data from a 10-year
      follow-up health survey were used. Successful aging indicators included basic and
      advanced physical function, depressive symptoms, cognitive function, emotional
      support, participation in productive activities, and life satisfaction. The
      stressors included life events and morbidity years of 10 chronic conditions. Loss
      of offspring increased the risk to physical health, psychological health, and
      life satisfaction. Being newly widowed was related to depressive symptoms,
      whereas being newly divorced increased the risk of poor social support. Morbidity
      years increased the risk of failure in successful aging, especially for stroke,
      respiratory system disease, diabetes, and cancer. Emotional health of the elderly
      should be carefully monitored after onset of life events and incidences of
      chronic conditions.

PMID- 21727084
TI  - Delivering diabetes care in the Philippines and Vietnam: policy and practice
      issues.
AB  - The aim of this study is the comparison of 2 studies looking at the barriers to
      access of diabetes care and medicines in the Philippines and Vietnam. These
      studies used the Rapid Assessment Protocol for Insulin Access. Diabetes care is
      provided in specialized facilities and appropriate referral systems are lacking.
      In Vietnam, no problems were reported with regard to diagnostic tools, whereas
      this was a concern in the public sector in the Philippines. Both countries had
      high prices for medicines in comparison to international standards. Availability
      of medicines was better in Vietnam than in the Philippines, especially with
      regard to insulin. This affected adherence as did a lack of patient education. As
      countries aim to provide health care to the majority of their populations through
      universal coverage, the challenge of diabetes cannot be neglected. Trying to
      achieve universal coverage in parallel to decentralization, national and local
      governments need adapted guidance for this.

PMID- 21727085
TI  - Modulation of the stability of the Salmonella fourU-type RNA thermometer.
AB  - RNA thermometers are translational control elements that regulate the expression
      of bacterial heat shock and virulence genes. They fold into complex secondary
      structures that block translation at low temperatures. A temperature increase
      releases the ribosome binding site and thus permits translation initiation. In
      fourU-type RNA thermometers, the AGGA sequence of the SD region is paired with
      four consecutive uridines. We investigated the melting points of the wild-type
      and mutant sequences. It was decreased by 5 degrees C when a stabilizing GC
      basepair was exchanged by an AU pair or increased by 11 degrees C when an
      internal AG mismatch was converted to a GC pair, respectively. Stabilized or
      destabilized RNA structures are directly correlated with decreased or increased
      in vivo gene expression, respectively. Mg(2+) also affected the melting point of
      the fourU thermometer. Variations of the Mg(2+) concentration in the
      physiological range between 1 and 2 mM translated into a 2.8 degrees C shift of
      the melting point. Thus, Mg(2+) binding to the hairpin RNA is regulatory
      relevant. Applying three different NMR techniques, two Mg(2+) binding sites were
      found in the hairpin structure. One of these binding sites could be identified as
      outer sphere binding site that is located within the fourU motif. Binding of the
      two Mg(2+) ions exhibits a positive cooperativity with a Hill coefficient of
      1.47. Free energy values DeltaG for Mg(2+) binding determined by NMR are in
      agreement with data determined from CD measurements.

PMID- 21727087
TI  - A genome wide study in fission yeast reveals nine PPR proteins that regulate
      mitochondrial gene expression.
AB  - Pentatricopeptide repeat (PPR) proteins are particularly numerous in plant
      mitochondria and chloroplasts, where they are involved in different steps of RNA
      metabolism, probably due to the repeated 35 amino acid PPR motifs that are
      thought to mediate interactions with RNA. In non-photosynthetic eukaryotes only a
      handful of PPR proteins exist, for example the human LRPPRC, which is involved in
      a mitochondrial disease. We have conducted a systematic study of the PPR proteins
      in the fission yeast Schizosaccharomyces pombe and identified, in addition to the
      mitochondrial RNA polymerase, eight proteins all of which localized to the
      mitochondria, and showed some association with the membrane. The absence of all
      but one of these PPR proteins leads to a respiratory deficiency and modified
      patterns of steady state mt-mRNAs or newly synthesized mitochondrial proteins.
      Some cause a general defect, whereas others affect specific mitochondrial RNAs,
      either coding or non-coding: cox1, cox2, cox3, 15S rRNA, atp9 or atp6, sometimes
      leading to secondary defects. Interestingly, the two possible homologs of LRPPRC,
      ppr4 and ppr5, play opposite roles in the expression of the cox1 mt-mRNA, ppr4
      being the first mRNA-specific translational activator identified in S. pombe,
      whereas ppr5 appears to be a general negative regulator of mitochondrial
      translation.

PMID- 21727086
TI  - Ubiquitination of human AP-endonuclease 1 (APE1) enhanced by T233E substitution
      and by CDK5.
AB  - Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene
      regulatory protein in mammalian cells, and was recently reported to be
      phosphorylated at Thr233 by CDK5. We here report that ubiquitination of T233E
      APE1, a mimicry of phospho-T233 APE1, was markedly increased in multiple cell
      lines. Expression of CDK5 enhanced monoubiquitination of endogenous APE1.
      Polyubiquitinated APE1 was decreased when K48R ubiquitin was expressed,
      suggesting that polyubiquitination was mediated mainly through Lys48 of
      ubiquitin. The ubiquitination activity of MDM2, consistent in its role for APE1
      ubiquitination, was increased for T233E APE1 compared to the wild-type APE1. In
      mouse embryonic fibroblasts lacking the MDM2 gene, ubiquitination of T233E APE1
      was still observed probably because of the decreased degradation activity for
      monoubiquitinated APE1 and because of backup E3 ligases in the cells.
      Monoubiquitinated APE1 was present in the nucleus, and analyzing global gene
      expression profiles with or without induction of a ubiquitin-APE1 fusion gene
      suggested that monoubiquitination enhanced the gene suppression activity of APE1.
      These data reveal a delicate balance of ubiquitination and phosphorylation
      activities that alter the gene regulatory function of APE1.

PMID- 21727088
TI  - Broad-spectrum aptamer inhibitors of HIV reverse transcriptase closely mimic
      natural substrates.
AB  - A detailed understanding of how aptamers recognize biological binding partners is
      of considerable importance in the development of oligonucleotide therapeutics.
      For antiviral nucleic acid aptamers, current models predict a correlation between
      broad-spectrum inhibition of viral proteins and suppression of emerging viral
      resistance, but there is little understanding of how aptamer structures
      contribute to recognition specificity. We previously established that two
      independent single-stranded DNA aptamers, R1T and RT1t49(-5), are potent
      inhibitors of reverse transcriptases (RTs) from diverse branches of the primate
      lentiviral family, including HIV-1, HIV-2 and SIV(cpz). In contrast, class 1 RNA
      pseudoknots, such as aptamer T1.1, are specific for RTs from only a few viral
      clades. Here, we map the binding interfaces of complexes formed between RT and
      aptamers R1T, RT1t49(-5) and T1.1, using mass spectrometry-based protein
      footprinting of RT and hydroxyl radical footprinting of the aptamers. These
      complementary methods reveal that the broad-spectrum aptamers make contacts
      throughout the primer-template binding cleft of RT. The double-stranded stems of
      these aptamers closely mimic natural substrates near the RNase H domain, while
      their binding within the polymerase domain significantly differs from RT
      substrates. These results inform our perspective on how sustained, broad-spectrum
      inhibition of RT can be achieved by aptamers.

PMID- 21727089
TI  - Temperature-induced melting of double-stranded DNA in the absence and presence of
      covalently bonded antitumour drugs: insight from molecular dynamics simulations.
AB  - The difference in melting temperature of a double-stranded (ds) DNA molecule in
      the absence and presence of bound ligands can provide experimental information
      about the stabilization brought about by ligand binding. By simulating the
      dynamic behaviour of a duplex of sequence 5'-d(TAATAACGGATTATT).5'
      d(AATAATCCGTTATTA) in 0.1 M NaCl aqueous solution at 400 K, we have characterized
      in atomic detail its complete thermal denaturation profile in <200 ns. A striking
      asymmetry was observed on both sides of the central CGG triplet and the strand
      separation process was shown to be strongly affected by bonding in the minor
      groove of the prototypical interstrand crosslinker mitomycin C or the
      monofunctional tetrahydroisoquinolines trabectedin (Yondelis), Zalypsis and
      PM01183. Progressive helix unzipping was clearly interspersed with some
      reannealing events, which were most noticeable in the oligonucleotides containing
      the monoadducts, which maintained an average of 6 bp in the central region at the
      end of the simulations. These significant differences attest to the demonstrated
      ability of these drugs to stabilize dsDNA, stall replication and transcription
      forks, and recruit DNA repair proteins. This stabilization, quantified here in
      terms of undisrupted base pairs, supports the view that these monoadducts can
      functionally mimic a DNA interstrand crosslink.

PMID- 21727090
TI  - Predicting the functional impact of protein mutations: application to cancer
      genomics.
AB  - As large-scale re-sequencing of genomes reveals many protein mutations,
      especially in human cancer tissues, prediction of their likely functional impact
      becomes important practical goal. Here, we introduce a new functional impact
      score (FIS) for amino acid residue changes using evolutionary conservation
      patterns. The information in these patterns is derived from aligned families and
      sub-families of sequence homologs within and between species using combinatorial
      entropy formalism. The score performs well on a large set of human protein
      mutations in separating disease-associated variants (~19 200), assumed to be
      strongly functional, from common polymorphisms (~35 600), assumed to be weakly
      functional (area under the receiver operating characteristic curve of ~0.86). In
      cancer, using recurrence, multiplicity and annotation for ~10 000 mutations in
      the COSMIC database, the method does well in assigning higher scores to more
      likely functional mutations ('drivers'). To guide experimental prioritization, we
      report a list of about 1000 top human cancer genes frequently mutated in one or
      more cancer types ranked by likely functional impact; and, an additional 1000
      candidate cancer genes with rare but likely functional mutations. In addition, we
      estimate that at least 5% of cancer-relevant mutations involve switch of
      function, rather than simply loss or gain of function.

PMID- 21727092
TI  - Enhanced activation of p21-activated kinase 1 in heart failure contributes to
      dephosphorylation of connexin 43.
AB  - AIMS: We previously showed decreased cellular coupling and dephosphorylation of
      the gap junctional protein connexin 43 (Cx43) in left ventricular (LV) myocytes
      from an arrhythmogenic rabbit model of non-ischaemic heart failure (HF) that was
      associated with a 2.5-fold increase in the amount of protein phosphatase type 2A
      (PP2A) co-localized with Cx43. Here, we further explore the molecular mechanisms
      of enhanced dephosphorylation of Cx43 in HF. p21-activated kinase 1 (PAK1) is a
      serine-threonine protein kinase that has been shown to activate PP2A. METHODS AND
      RESULTS: We found that total PAK1 and activated PAK1 (PAK1-P(Thr423)) were both
      increased in HF rabbit LV (vs. controls). PAK1 co-immunoprecipitated (co-IP'd)
      with Cx43 protein and, with HF, co-IP'd PAK1 and PAK1-P(Thr423) were increased.
      With failing human LV, PAK1 total protein and PAK1-P(Thr423) were also increased
      globally and locally (co-IP'd with Cx43). To further explore the role of PAK1 in
      modulating Cx43 dephosphorylation and intercellular coupling, we overexpressed
      active PAK1 in isolated LV myocytes from control rabbits and in HEK293 cells with
      genetically modified overexpression of Cx43 (HEK293-Cx43). PAK1 overexpression in
      both rabbit myocytes and HEK293-Cx43 cells significantly increased PP2A activity
      (globally and at the level of Cx43), increased dephosphorylated Cx43, and
      markedly reduced intercellular dye coupling. These effects were attenuated with
      PP2A inhibition using okadaic acid (10 nM). CONCLUSIONS: PAK1 and PP2A are
      integral components of a macromolecular complex with cardiac Cx43, and increased
      activation of associated PAK1 can contribute to enhanced Cx43 dephosphorylation
      and impaired intercellular coupling that may underlie slow conduction in HF.

PMID- 21727093
TI  - The value of a family history of sudden death in patients with diagnostic type I
      Brugada ECG pattern.
AB  - AIMS: We sought to investigate the value of a family history of sudden death (SD)
      in Brugada syndrome (BS). METHODS AND RESULTS: Two hundred and eighty consecutive
      patients (mean age: 41 +/- 18 years, 168 males) with diagnostic type I Brugada
      ECG pattern were included. Sudden death occurred in 69 (43%) of 157 families. One
      hundred and ten SDs were analysed. During follow-up VF (ventricular fibrillation)
      or SD-free survival rate was not different between patients with or without a
      family history of SD of a first-degree relative, between patients with or without
      a family history of multiple SD of a first-degree relative at any age and between
      patients with or without a family history of SD in first-degree relatives <=35
      years. One patient had family history of SD of two first-degree relative <=35
      years with arrhythmic event during follow-up. In univariate analysis male gender
      (P = 0.01), aborted SD (P < 0.001), syncope (P = 0.04), spontaneous type I ECG (P
      < 0.001), and inducibility during electrophysiological (EP) study (P < 0.001)
      were associated with worse prognosis. The absence of syncope, aborted SD,
      spontaneous type I ECG, and inducibility during EP study was associated with a
      significantly better prognosis (P < 0.001). CONCLUSION: Family history of SD is
      not predictive for future arrhythmic events even if considering only SD in first
      degree relatives or SD in first-degree relatives at a young age. The absence of
      syncope, aborted SD, spontaneous type I ECG, and inducibility during EP study is
      associated with a good five-year prognosis.

PMID- 21727091
TI  - ASF1A and ATM regulate H3K56-mediated cell-cycle checkpoint recovery in response
      to UV irradiation.
AB  - Successful DNA repair within chromatin requires coordinated interplay of histone
      modifications, chaperones and remodelers for allowing access of repair and
      checkpoint machineries to damaged sites. Upon completion of repair, ordered
      restoration of chromatin structure and key epigenetic marks herald the cell's
      normal function. Here, we demonstrate such a restoration role of H3K56
      acetylation (H3K56Ac) mark in response to ultraviolet (UV) irradiation of human
      cells. A fast initial deacetylation of H3K56 is followed by full renewal of an
      acetylated state at ~24-48 h post-irradiation. Histone chaperone, anti-silencing
      function-1 A (ASF1A), is crucial for post-repair H3K56Ac restoration, which in
      turn, is needed for the dephosphorylation of gamma-H2AX and cellular recovery
      from checkpoint arrest. On the other hand, completion of DNA damage repair is not
      dependent on ASF1A or H3K56Ac. H3K56Ac restoration is regulated by ataxia
      telangiectasia mutated (ATM) checkpoint kinase. These cross-talking molecular
      cellular events reveal the important pathway components influencing the
      regulatory function of H3K56Ac in the recovery from UV-induced checkpoint arrest.

PMID- 21727094
TI  - Double mechanical prosthesis, correct international normalized ratio, and giant
      atrial mass.

PMID- 21727095
TI  - Porcelain aorta.

PMID- 21727096
TI  - Heart health when life is satisfying: evidence from the Whitehall II cohort
      study.
AB  - AIMS: Negative psychological states such as stress and depression are associated
      with increased risk of coronary heart disease (CHD), but it is unclear whether
      some positive states are protective. We investigated satisfaction with specific
      life domains as predictors of incident CHD. METHODS AND RESULTS: Coronary risk
      factors and satisfaction within seven life domains (e.g. job and family) were
      assessed in 7956 initially healthy members of the Whitehall II cohort. Incident
      CHD (angina, non-fatal myocardial infarction, or death from CHD) was ascertained
      from medical screening, hospital data, and registry linkage over five person
      years of follow-up. Satisfaction averaged across domains was associated with
      reduced CHD risk (HR: 0.87; 95% CI: 0.78-0.98), controlling for demographic
      characteristics, health behaviours, blood pressure, and metabolic functioning.
      Associations with CHD risk were evident for satisfaction in four life domains
      one's job, family, sex life, and self, but not one's love relationship, leisure
      activities, or standard of living. When examining CHD outcomes separately,
      average domain satisfaction was associated with angina but not myocardial
      infarction or coronary death. CONCLUSIONS: Satisfaction in most life domains was
      associated with reduced CHD risk, with definite angina being mostly responsible
      for this association. These findings suggest that satisfaction with life may
      promote heart health. Further research should examine whether interventions to
      enhance life satisfaction in specific domains reduce CHD risk and whether life
      satisfaction is primarily associated with atherosclerosis rather than thrombotic
      factors associated with plaque rupture.

PMID- 21727098
TI  - Dopamine-dependent reinforcement of motor skill learning: evidence from Gilles de
      la Tourette syndrome.
AB  - Reinforcement learning theory has been extensively used to understand the neural
      underpinnings of instrumental behaviour. A central assumption surrounds dopamine
      signalling reward prediction errors, so as to update action values and ensure
      better choices in the future. However, educators may share the intuitive idea
      that reinforcements not only affect choices but also motor skills such as typing.
      Here, we employed a novel paradigm to demonstrate that monetary rewards can
      improve motor skill learning in humans. Indeed, healthy participants
      progressively got faster in executing sequences of key presses that were
      repeatedly rewarded with 10 euro compared with 1 cent. Control tests revealed
      that the effect of reinforcement on motor skill learning was independent of
      subjects being aware of sequence-reward associations. To account for this
      implicit effect, we developed an actor-critic model, in which reward prediction
      errors are used by the critic to update state values and by the actor to
      facilitate action execution. To assess the role of dopamine in such computations,
      we applied the same paradigm in patients with Gilles de la Tourette syndrome, who
      were either unmedicated or treated with neuroleptics. We also included patients
      with focal dystonia, as an example of hyperkinetic motor disorder unrelated to
      dopamine. Model fit showed the following dissociation: while motor skills were
      affected in all patient groups, reinforcement learning was selectively enhanced
      in unmedicated patients with Gilles de la Tourette syndrome and impaired by
      neuroleptics. These results support the hypothesis that overactive dopamine
      transmission leads to excessive reinforcement of motor sequences, which might
      explain the formation of tics in Gilles de la Tourette syndrome.

PMID- 21727099
TI  - Original technique to close the transrectal viscerotomy access in a NOTES
      transrectal and transgastric segmental colectomy.
AB  - Segmental colectomy is an ideal procedure for natural orifice transluminal
      endoscopic surgery (NOTES). Transanal endoscopic approaches have enabled
      rectosigmoid colectomy through a viscerotomy that is resected with the specimen.
      To extend NOTES segmental colectomy to the entire colon and beyond, a rectal
      viscerotomy will have to be safely and effectively closed at the end of the
      procedure. A new technique for rectal viscerotomy closure using a circular EEA
      hemorrhoid and prolapse stapler with DST series technology (Covidien) is
      described.

PMID- 21727097
TI  - Socio-demographic predictors of dimensions of the AUDIT score in a population
      sample of working-age men in Izhevsk, Russia.
AB  - AIMS: To investigate the relationship between socio-demographic factors and
      alcohol drinking patterns identified through a formal analysis of the factor
      structure of the Alcohol Use Disorders Identification Test (AUDIT) score in a
      population sample of working-age men in Russia. METHODS: In 2008-2009, a sample
      of 1005 men aged 25-59 years living in Izhevsk, Russia were interviewed and
      information collected about socio-demographic circumstances. Responses to the
      AUDIT questions were obtained through a self-completed questionnaire. Latent
      dimensions of the AUDIT score were determined using confirmatory factor analysis
      and expressed as standard deviation (SD) units. Structural equation modelling was
      used to estimate the strength of association of these dimensions with socio
      demographic variables. RESULTS: The AUDIT was found to have a two-factor
      structure: alcohol consumption and alcohol-related problems. Both dimensions were
      higher in men who were unemployed seeking work compared with those in regular
      paid employment. For consumption, there was a difference of 0.59 SDs, (95%
      confidence interval (CI): 0.23, 0.88) and for alcohol-related problems one of
      0.66 SD (95% CI: 0.31, 1.00). Alcohol-related problems were greater among less
      educated compared with more educated men (P-value for trend = 0.05), while
      consumption was not related to education. Similar results were found for
      associations with an amenity index based on car ownership and central heating.
      Neither dimension was associated with marital status. While we found evidence
      that the consumption component of AUDIT was underestimated, this did not appear
      to explain the associations of this dimension with socio-demographic factors.
      CONCLUSIONS: Education and amenity index, both measures of socio-economic
      position, were inversely associated with alcohol-related problems but not with
      consumption. This discordance suggests that self-reported questions on frequency
      and volume may be less sensitive markers of socio-economic variation in drinking
      than are questions about dependence and harm. Further investigation of the
      validity of the consumption component of AUDIT in Russia is warranted as it
      appears that the concept of a standard 'drink' as used in the instrument is not
      understood.

PMID- 21727100
TI  - Sustaining and spreading the reduction of adverse drug events in a multicenter
      collaborative.
AB  - OBJECTIVES: Adverse drug events (ADEs) occur more frequently in pediatric
      patients than adults. ADEs frequently cause serious harm to children and increase
      the cost of care. The purpose of this study was to decrease ADEs by targeting the
      entire medication-delivery system for all high-risk medications. METHODS:
      Thirteen freestanding children's hospitals participated in this ADE
      collaborative. An advisory panel developed a change package of interventions that
      consisted of standardization of medication-ordering (eg, consensus-based
      protocols and order sets and high-alert medication protocols), reliable
      medication-dispensing processes (eg, automated dispensing cabinets and redesign
      of floor stock procedures), reliable medication-administration processes (eg,
      safe pump use and reducing interruptions), improvement of patient safety culture
      (eg, safety-culture changes and reduction of staff intimidation), and clinical
      decision support (eg, increase ADE detection and redesign care systems). ADE
      rates were compared from the 3-month baseline period to quarters of the 12-month
      intervention phase. ADE rates were categorized further as opioid related and
      other medication related. RESULTS: From baseline to the final quarter, the
      collaborative resulted in a 42% decrease in total ADEs, a 51% decrease in opioid
      related ADEs, and a 41% decrease in other medication ADEs. CONCLUSION: A
      pediatric collaborative that targeted the medication-delivery system decreased
      the rate of ADEs at participating institutions.

PMID- 21727101
TI  - Identification of developmental-behavioral problems in primary care: a systematic
      review.
AB  - CONTEXT: Recent mandates and recommendations for formal screening programs are
      based on the claim that pediatric care providers underidentify children with
      developmental-behavioral disorders, yet the research to support this claim has
      not been systematically reviewed. OBJECTIVE: To review research literature for
      studies regarding pediatric primary care providers' identification of
      developmental-behavioral problems in children. METHODS: On the basis of a Medline
      search conducted on September 22, 2010, using relevant key words, we identified
      539 articles for review. We included studies that (1) were conducted in the
      United States, (2) were published in peer-reviewed journals, (3) included data
      that addressed pediatric care providers' identification of developmental
      behavioral problems in individual patients, (4) included an independent
      assessment of patients' developmental-behavioral problems, such as diagnostic
      interviews or validated screening instruments, and (5) reported data sufficient
      to calculate sensitivity and specificity. Studies were not limited by sample
      size. Eleven articles met these criteria. We used Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS) criteria to evaluate study quality. Although
      the studies were similar in many ways, heterogeneous methodology precluded a meta
      analysis. RESULTS: Sensitivities for pediatric care providers ranged from 14% to
      54%, and specificities ranged from 69% to 100%. The authors of 1 outlier study
      reported a sensitivity of 85% and a specificity of 61%. CONCLUSIONS:
      Pediatricians are often the first point of entry into developmental and mental
      health systems. Knowing their accuracy in identifying children with developmental
      behavioral disabilities is essential for implementing optimal evaluation programs
      and achieving timely identification. Moreover, these statistics are important to
      consider when planning large-scale screening programs.

PMID- 21727102
TI  - Dermatophytid in tinea capitis: rarely reported common phenomenon with clinical
      implications.
AB  - Tinea capitis may be associated with a dermatophytid, which appears as a
      disseminated eczematous eruption. This phenomenon may occur before or after
      initiation of systemic antifungal drug therapy and is not an indication for
      stopping medication. We present here a series of cases that involve 5 children
      with tinea capitis who developed a dermatophytid before or during the course of
      their management. In each child, the eruption resolved despite continuation of
      oral antifungal therapy. Our experience suggests that dermatophytid secondary to
      tinea capitis is much more common than reported. Furthermore, parents and
      clinicians frequently mistake dermatophytid for drug allergy. Recognition of this
      phenomenon, distinction of dermatophytid from drug allergy, and continuation of
      systemic treatment is essential for clearing the infection and dermatophytid.

PMID- 21727103
TI  - Accuracy of a novel system for oxygen delivery to small children.
AB  - OBJECTIVE: Oxygen therapy for infants and small children in developing countries
      is often not available. Entrainment devices may provide an accurate and precise
      concentration of oxygen when used at the flow rates appropriate for infants and
      small children. METHODS: A continuously adjustable entrainment device was tested
      to determine the concentrations and flows of oxygen delivered by using low inlet
      flow rates suitable for therapy for infants and small children and 3 distinct
      oxygen delivery systems that varied in their resistive load. RESULTS: The use of
      long and large bore, low resistance tubing (similar to a mask) resulted in the
      delivery of oxygen concentrations that tracked closely (accurate and precise) to
      values indicated by the entrainment device. The directly connected system with
      lower resistance (similar to a hood) produced a similar profile of concentrations
      and flow rates to the large bore tubing but with even greater accuracy. The use
      of a long and narrow tubing with higher resistance (similar to a cannula) did not
      deliver accurate oxygen concentrations. In fact, this high-resistance system
      failed to work as intended, and instead of entraining air, a large proportion
      (sometimes >50%) of the oxygen delivered to the entrainment device was ejected
      through its vents. CONCLUSIONS: Entrainment devices can deliver accurate oxygen
      concentrations at low flow rates if used with low resistance delivery systems;
      however, entrainment devices are not suitable for use with high resistance
      delivery systems such as a standard nasal cannula.

PMID- 21727104
TI  - Longitudinal changes in active transportation to school in Canadian youth aged 6
      through 16 years.
AB  - BACKGROUND: Concern has been raised regarding the increased prevalence of
      physical inactivity among children. Active transportation, such as walking and
      cycling to school, is an opportunity for children to be physically active.
      OBJECTIVE: To identify the sociodemographic predictors of active transportation
      to schools across time among school-aged children participating in the Canadian
      National Longitudinal Survey of Children and Youth (NLSCY). METHODS: The sample
      included 7690 school-aged children attending public schools who were drawn from
      cycle 2 (1996 and 1997) of the Canadian NLSCY. Data were collected through
      interviews with the person most knowledgeable about the child. Parents were asked
      how their child usually gets to school. Responses were dichotomized into active
      (walking or bicycling) or inactive (school bus, public transit, is driven, or
      multiple) modes. Using 3 waves of data from the Canadian NLSCY (1996-2001), we
      estimated the effect of sociodemographic factors on the likelihood of active
      transportation to school across time using random-effects models. RESULTS:
      Longitudinal analyses indicated that as children aged, the likelihood of using
      active transportation to school increased, peaked at the age of 10 years, and
      then decreased. Urban settings (odds ratio [OR]: 3.66 [95% confidence interval
      (CI): 3.23-4.15]), households with inadequate income (OR: 1.21 [95% CI: 1.06
      1.38]), living with 1 parent (OR: 1.46 [95% CI: 1.29-1.65]), and having an older
      sibling living at home (OR: 1.14 [95% CI: 1.04-1.25]) were significant predictors
      of active transportation to school at baseline and carried through across time.
      CONCLUSIONS: Understanding the factors that influence active transportation may
      support its adoption by children, which in turn may contribute to meeting
      physical activity guidelines.

PMID- 21727105
TI  - Composite measures quantify households' obesogenic potential and adolescents'
      risk behaviors.
AB  - OBJECTIVE: The aims of this study were to generate composite measures quantifying
      a household's obesogenic potential and to examine the relationship of the
      composite variables with older children's eating, physical activity (PA), and
      small screen recreation. METHODS: Data were from surveys with 1685 child-parent
      pairs in which the child was in grade 6, 8, or 10 (mean age: 14 years). Composite
      measures of the obesogenic household environment were generated from 11 measures
      using nonlinear principal components analysis. Associations between the composite
      measures and the children's healthy and unhealthy food intake, PA, and screen
      time were tested (adjusting for demographic characteristics). RESULTS: Two scales
      were generated: (1) obesogenic control, which clustered together factors that
      mitigate risk; and (2) obesogenic risk. Higher scores on the control scale were
      associated with higher adolescent intake of healthy foods, lower intake of
      unhealthy foods, higher PA, and less screen time. Higher scores on the risk scale
      were associated with lower adolescent intake of healthy foods, higher intake of
      unhealthy foods, lower PA, and more screen time. There were significant 2-way
      interactions between the scales for soft drink consumption and PA. CONCLUSIONS:
      Household obesogenic potential may be quantified as 2 factors reflecting
      cumulative risk and control practices. These factors have both additive
      associations with obesogenic behaviors and, in some cases, modify each other,
      suggesting that a healthy home environment requires attention to both. Health
      promotion messages could incorporate these 2 different but interacting factors
      that parents can use to modify the obesogenic potential of their household.

PMID- 21727106
TI  - Late talking and the risk for psychosocial problems during childhood and
      adolescence.
AB  - OBJECTIVE: Although many toddlers with expressive vocabulary delay ("late
      talkers") present with age-appropriate language skills by the time they are of
      school age, little is known about their broader behavioral and emotional profile.
      The aim of this study was to determine whether late talkers are at increased risk
      for behavioral and emotional problems during childhood and adolescence. PATIENTS
      AND METHODS: Participants were from the Western Australian Pregnancy Cohort
      Study. Early expressive vocabulary was measured by parent report at age 2 years
      using the Language Development Survey. Late talkers were defined as toddlers who
      scored at or below the 15th percentile on the Language Development Survey for
      their gender but were screened not to have any other developmental delays. The
      Child Behavior Checklist was used to measure problem child behavior with
      continuous z scores and clinical thresholds at ages 2, 5, 8, 10, 14, and 17
      years. Potential confounders included maternal and family sociodemographic
      characteristics as well as prenatal smoking and alcohol exposure. RESULTS: At age
      2 years, late talkers (n = 142) had higher Child Behavior Checklist scores
      (representing poorer behavior) than control toddlers (n = 1245) in total,
      internalizing, and externalizing scales and higher risk for clinically
      significant internalizing and externalizing problems. Regression models,
      incorporating the confounding variables, revealed no association between late
      talking status at age 2 years and behavioral and emotional problems at the 5-, 8
      , 10-, 14-, and 17-year follow-ups. CONCLUSIONS: Expressive vocabulary delay at
      the age of 2 years is not in itself a risk factor for later behavioral and
      emotional disturbances.

PMID- 21727107
TI  - Hepatitis A infection in recent international adoptees and their contacts in
      Minnesota, 2007-2009.
AB  - OBJECTIVE: The goal of this study was to describe hepatitis A-infected adoptees
      and the risk of transmission to their contacts. METHODS: This was a retrospective
      review of adoptee-associated cases of hepatitis A and hepatitis A-infected
      adoptees identified in Minnesota from 2007 through 2009. RESULTS: From 2007
      through 2009 in Minnesota, 10 cases of hepatitis A, including 1 fulminant case,
      were associated with international adoptees. Eight cases were direct contacts of
      a hepatitis A-infected adoptee, and 2 other cases secondary contacts of an
      adoptee. During the same period, hepatitis A infection was identified in 21
      recently arrived foreign-born adoptees; all were younger than 60 months of age,
      and only 6 were symptomatic. CONCLUSIONS: Clinicians should be aware that
      transmission of hepatitis A may occur among both direct and secondary contacts of
      young children recently adopted from hepatitis A-endemic areas and that infected
      young children may be asymptomatic. Household members and other close contacts of
      international adoptees should be counseled about hepatitis A prevention,
      including vaccination. In addition, screening for hepatitis A should be
      considered for recently arrived adoptees from endemic areas.

PMID- 21727109
TI  - Novel protagonists in autoinflammatory arthritis of familial Mediterranean fever.
AB  - To clarify mechanisms responsible for the self-limiting and nonerosive features
      of autoinflammatory joint disease in familial Mediterranean fever (FMF), we
      performed a study on synovial tissue obtained surgically from an acutely inflamed
      hip joint from a boy feared to have septic arthritis but later found to be
      homozygous for mutation M694I in pyrin/marenostrin. We defined by immunohistology
      the infiltrating cells and examined the in situ expression of plausible
      protagonists in synovitis of FMF: myeloperoxidase, lysozyme, galectin 1, galectin
      3, p65 (RelA)/nuclear factor kappaB, inducible nitric-oxide synthase,
      cyclooxygenase 2, and cleaved caspase 3. Neutrophils deficient in myeloperoxidase
      and lysozyme, macrophages, and mast cells outnumbered T and B lymphocytes as well
      as plasma cells. Among cells of adaptive immunity, B lymphocytes were
      predominant. Galectin 1 was detected in numerous cells of the innate immune
      system throughout the synovial tissue, whereas expression of galectin 3 was less
      abundant and scattered. p65 (RelA)/nuclear factor kappaB and inducible nitric
      oxide synthase were both upregulated in most of the infiltrating cells.
      Cyclooxygenase 2 expression was low, and cleaved caspase 3 was undetectable. We
      conclude that the exquisitely inflammatory yet nondestructive character of FMF
      arthritis could correlate with the presence of nonpathogenic neutrophils lacking
      effector molecules and the widespread expression of anti-inflammatory galectin 1
      in regulatory cells of the innate immune system. Intrinsic apoptosis seemed
      irrelevant for confining synovial autoinflammation, but regulation through
      pyroptosis or the adaptive immune system remains possible.

PMID- 21727108
TI  - Immunization of preterm infants with 10-valent pneumococcal conjugate vaccine.
AB  - OBJECTIVE: The safety and immunogenicity of the 10-valent pneumococcal
      nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in
      preterm infants were assessed in this study. METHODS: Three parallel groups of
      infants received 3-dose primary immunization with PHiD-CV at 2, 4, and 6 months
      of age and a booster dose at 16 to 18 months: preterm I (gestation period >= 27
      and <31 weeks, N = 50); preterm II (>=31 and <37 weeks, N = 87); and term (>=37
      weeks, N = 149). Solicited symptoms and adverse events were recorded. Immune
      responses to PHiD-CV and coadministered vaccine antigens were measured. RESULTS:
      The incidence of solicited general symptoms was similar across groups, and the
      frequency of grade 3 general symptoms was low. Incidences of redness and swelling
      were generally lower in preterm infants. PHiD-CV was immunogenic for each of the
      10 vaccine pneumococcal serotypes (postprimary, >=92.7% of infants reached enzyme
      linked immunosorbent assay antibody concentrations >= 0.2 MUg/mL and postbooster,
      >=97.6%) and for protein D, with a trend for lower postprimary geometric mean
      antibody concentrations and opsonophagocytic activity (OPA) titers in preterm
      infants for some pneumococcal serotypes. Postbooster, >=91.9% of subjects in each
      group had an OPA titer >= 8 for each of the vaccine serotypes. Pneumococcal
      antibody concentrations and OPA titers after priming and booster vaccination were
      comparable between the 2 preterm groups. CONCLUSIONS: PHiD-CV was well tolerated
      and immunogenic in preterm infants when given as a 3-dose primary vaccination,
      with robust enzyme-linked immunosorbent assay antibody and OPA booster responses
      in the second year of life.

PMID- 21727110
TI  - Subcutaneous fat necrosis after moderate therapeutic hypothermia in neonates.
AB  - Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy
      is rapidly becoming standard clinical practice. We report here 12 cases of
      subcutaneous fat necrosis among 1239 cases registered with a national registry of
      newborns treated with moderate whole-body hypothermia. All the infants suffered
      from perinatal asphyxia and hypoxic-ischemic encephalopathy. Moderate-to-severe
      hypercalcemia was identified in 8 of 10 infants with blood calcium measurements.
      In all cases the skin lesions appeared after completion of the cooling treatment.
      Our data suggest that prolonged moderate hypothermia is an actual risk factor for
      subcutaneous fat necrosis. Because the lesions often develop several days after
      birth, physicians need to be aware of this condition as a possible complication
      in infants treated with moderate hypothermia after asphyxia. Blood calcium levels
      need to be monitored in affected infants.

PMID- 21727111
TI  - The need for vigilance: the case of a false-negative newborn screen for cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is the most common life-limiting recessive genetic disorder
      in the white population. CF is caused by abnormalities in the gene that codes for
      the cystic fibrosis transmembrane conductance regulator protein (CFTR) and may
      result in severe chronic lung disease, poor growth, and malnutrition. Physicians
      often do not consider CF in the differential diagnosis of an infant with failure
      to thrive in the presence of a negative newborn screening (NBS) result. In
      Minnesota, newborn infants are screened for CF by immunoreactive trypsinogen
      (IRT) testing followed by DNA analysis if the IRT screen result is abnormal. All
      positive NBS results are followed by confirmatory sweat-testing by pilocarpine
      iontophoresis. We present here the case of a 1-month-old white boy with failure
      to thrive, chronic diarrhea, and severe malnutrition. Minnesota state CF NBS
      results were negative at birth (IRT: 43 ng/mL [96% cutoff value: 52 ng/mL]).
      Clinical symptoms resulted in sweat-testing by Gibson-Cooke pilocarpine
      iontophoresis at 1 month of age, and the result was positive (102 mmol Cl(-)/L
      [normal: <=30 mmol Cl(-)/L]). CFTR mutation analysis confirmed a homozygous
      f508del genotype, and stool pancreatic elastase testing revealed severe exocrine
      pancreatic insufficiency. This case represents the first known false-negative
      result in Minnesota since the initiation of NBS for CF in 2006, which illustrates
      the importance of considering CF in the evaluation of an infant with failure to
      thrive and symptoms of malabsorption, regardless of NBS results.

PMID- 21727112
TI  - New directions in spintronics.
AB  - Conventional microelectronics exploits only the charge degree of freedom of the
      electron. Bringing the spin degree of freedom to bear on sensing, radio
      frequency, memory and logic applications opens up new possibilities for 'more
      than Moore' devices incorporating magnetic components that can couple to an
      external field, store a bit of data or represent a Boolean state. Moreover, the
      electron spin is an archetypal two-state quantum system that is an excellent
      candidate for a solid-state realization of a qubit.

PMID- 21727113
TI  - Tunnel magnetoresistance effect and magnetic damping in half-metallic Heusler
      alloys.
AB  - Some full-Heusler alloys, such as Co(2)MnSi and Co(2)MnGe, are expected to be
      half-metallic ferromagnetic material, which has complete spin polarization. They
      are the most promising materials for realizing half-metallicity at room
      temperature owing to their high Curie temperature. We demonstrate a huge tunnel
      magnetoresistance effect in a magnetic tunnel junction using a Co(2)MnSi Heusler
      alloy electrode. This result proves high spin polarization of the Heusler alloy.
      We also demonstrate a small magnetic damping constant in Co(2)FeAl epitaxial
      film. The very high spin polarization and small magnetic constant of Heusler
      alloys will be a great advantage for future spintronic device applications.

PMID- 21727114
TI  - Organic spintronics.
AB  - Organic semiconductors are emerging materials in the field of spintronics.
      Successful achievements include their use as a tunnel barrier in magnetoresistive
      tunnelling devices and as a medium for spin-polarized current in transport
      devices. In this paper, we give an overview of the basic concepts of spin
      transport in organic semiconductors and present the results obtained in the
      field, highlighting the open questions that have to be addressed in order to
      improve devices performance and reproducibility. The most challenging
      perspectives will be discussed and a possible evolution of organic spin devices
      featuring multi-functional operation is presented.

PMID- 21727115
TI  - Multi-ferroic and magnetoelectric materials and interfaces.
AB  - The existence of multiple ferroic orders in the same material and the coupling
      between them have been known for decades. However, these phenomena have mostly
      remained the theoretical domain owing to the fact that in single-phase materials
      such couplings are rare and weak. This situation has changed dramatically
      recently for at least two reasons: first, advances in materials fabrication have
      made it possible to manufacture these materials in structures of lower
      dimensionality, such as thin films or wires, or in compound structures such as
      laminates and epitaxial-layered heterostructures. In these designed materials,
      new degrees of freedom are accessible in which the coupling between ferroic
      orders can be greatly enhanced. Second, the miniaturization trend in conventional
      electronics is approaching the limits beyond which the reduction of the
      electronic element is becoming more and more difficult. One way to continue the
      current trends in computer power and storage increase, without further size
      reduction, is to use multi-functional materials that would enable new device
      capabilities. Here, we review the field of multi-ferroic (MF) and magnetoelectric
      (ME) materials, putting the emphasis on electronic effects at ME interfaces and
      MF tunnel junctions.

PMID- 21727116
TI  - Antiferromagnetic metal spintronics.
AB  - In this brief review, we explain the theoretical basis for the notion that spin
      transfer torques (STTs) and giant-magnetoresistance effects can, in principle,
      occur in circuits containing only normal and antiferromagnetic (AFM) materials,
      and for the notion that antiferromagnets can play a role in STT phenomena in
      circuits containing both ferromagnetic and AFM elements. We review the
      experimental literature that provides partial evidence for these AFM spintronic
      effects but demonstrates that, like exchange-bias effects, they are sensitive to
      details of interface structure that are not always under experimental control.
      Finally, we speculate briefly on some strategies that might advance progress.

PMID- 21727117
TI  - Ultrafast magnetization dynamics of spintronic nanostructures.
AB  - The ultrafast (sub-nanosecond) magnetization dynamics of ferromagnetic thin films
      and elements that find application in spintronic devices is reviewed. The major
      advances in the understanding of magnetization dynamics in the two decades since
      the discovery of giant magnetoresistance and the prediction of spin-transfer
      torque are discussed, along with the plethora of new experimental techniques
      developed to make measurements on shorter length and time scales. Particular
      consideration is given to time-resolved measurements of the magneto-optical Kerr
      effect, and it is shown how a succession of studies performed with this technique
      has led to an improved understanding of the dynamics of nanoscale magnets. The
      dynamics can be surprisingly rich and complicated, with the latest studies of
      individual nanoscale elements showing that the dependence of the resonant mode
      spectrum upon the physical structure is still not well understood. Finally, the
      article surveys the prospects for development of high-frequency spintronic
      devices and highlights areas in which further study of fundamental properties
      will be required within the coming decade.

PMID- 21727118
TI  - Manipulation of spin currents in metallic systems.
AB  - The transport properties of diffusive spin currents have been investigated in
      lateral ferromagnetic/non-magnetic metal hybrid structures. The spin diffusion
      processes were found to be strongly dependent on the magnitude of the spin
      resistances of connected materials. Efficient spin injection and detection are
      accomplished by optimizing the junction structures on the basis of the spin
      resistance circuitry. The magnetization switching of a nanoscale ferromagnetic
      particle and also room temperature spin Hall effect measurements were realized by
      using an efficient pure-spin-current injection.

PMID- 21727119
TI  - Single electron spintronics.
AB  - Single electron electronics is now well developed, and allows the manipulation of
      electrons one-by-one as they tunnel on and off a nanoscale conducting island. In
      the past decade or so, there have been concerted efforts in several laboratories
      to construct single electron devices incorporating ferromagnetic components in
      order to introduce spin functionality. The use of ferromagnetic electrodes with a
      non-magnetic island can lead to spin accumulation on the island. On the other
      hand, making the dot also ferromagnetic introduces new physics such as tunnelling
      magnetoresistance enhancement in the cotunnelling regime and manifestations of
      the Kondo effect. Such nanoscale islands are also found to have long spin
      lifetimes. Conventional spintronics makes use of the average spin-polarization of
      a large ensemble of electrons: this new approach offers the prospect of accessing
      the quantum properties of the electron, and is a candidate approach to the
      construction of solid-state spin-based qubits.

PMID- 21727120
TI  - Current-induced spin-orbit torques.
AB  - The ability to reverse the magnetization of nanomagnets by current injection has
      attracted increased attention ever since the spin-transfer torque mechanism was
      predicted in 1996. In this paper, we review the basic theoretical and
      experimental arguments supporting a novel current-induced spin torque mechanism
      taking place in ferromagnetic (FM) materials. This effect, hereafter named spin
      orbit (SO) torque, is produced by the flow of an electric current in a
      crystalline structure lacking inversion symmetry, which transfers orbital angular
      momentum from the lattice to the spin system owing to the combined action of SO
      and exchange coupling. SO torques are found to be prominent in both FM metal and
      semiconducting systems, allowing for great flexibility in adjusting their
      orientation and magnitude by proper material engineering. Further directions of
      research in this field are briefly outlined.

PMID- 21727121
TI  - Nanopillar junctions.
AB  - The fabrication of nanopillar devices has been essential to the understanding and
      development of metallic spin electronics. This paper discusses the processes that
      can be used for the fabrication of such structures and the challenges in which
      they present, with particular emphasis on extreme sub-micrometre pillar
      structures suitable for the study of spin-transfer torque effects.

PMID- 21727122
TI  - Nanowire spintronics for storage class memories and logic.
AB  - Patterned magnetic nanowires are extremely well suited for data storage and logic
      devices. They offer non-volatile storage, fast switching times, efficient
      operation and a bistable magnetic configuration that are convenient for
      representing digital information. Key to this is the high level of control that
      is possible over the position and behaviour of domain walls (DWs) in magnetic
      nanowires. Magnetic random access memory based on the propagation of DWs in
      nanowires has been released commercially, while more dynamic shift register
      memory and logic circuits have been demonstrated. Here, we discuss the present
      standing of this technology as well as reviewing some of the basic DW effects
      that have been observed and the underlying physics of DW motion. We also discuss
      the future direction of magnetic nanowire technology to look at possible
      developments, hurdles to overcome and what nanowire devices may appear in the
      future, both in classical information technology and beyond into quantum
      computation and biology.

PMID- 21727123
TI  - Quantum control in spintronics.
AB  - Superposition and entanglement are uniquely quantum phenomena. Superposition
      incorporates a phase that contains information surpassing any classical mixture.
      Entanglement offers correlations between measurements in quantum systems that are
      stronger than any that would be possible classically. These give quantum
      computing its spectacular potential, but the implications extend far beyond
      quantum information processing. Early applications may be found in entanglement
      enhanced sensing and metrology. Quantum spins in condensed matter offer promising
      candidates for investigating and exploiting superposition and entanglement, and
      enormous progress is being made in quantum control of such systems. In gallium
      arsenide (GaAs), individual electron spins can be manipulated and measured, and
      singlet-triplet states can be controlled in double-dot structures. In silicon,
      individual electron spins can be detected by ionization of phosphorus donors, and
      information can be transferred from electron spins to nuclear spins to provide
      long memory times. Electron and nuclear spins can be manipulated in nitrogen
      atoms incarcerated in fullerene molecules, which in turn can be assembled in
      ordered arrays. Spin states of charged nitrogen vacancy centres in diamond can be
      manipulated and read optically. Collective spin states in a range of materials
      systems offer scope for holographic storage of information. Conditions are now
      excellent for implementing superposition and entanglement in spintronic devices,
      thereby opening up a new era of quantum technologies.

PMID- 21727124
TI  - The evolving biology of cell reprogramming.
AB  - Modern stem cell biology has achieved a transformation that was thought by many
      to be every bit as unattainable as the ancient alchemists' dream of transforming
      base metals into gold. Exciting opportunities arise from the process known as
      'cellular reprogramming' in which cells can be reliably changed from one tissue
      type to another. This is enabling novel approaches to more deeply investigate the
      fundamental basis of cell identity. In addition, new opportunities have also been
      created to study (perhaps even to treat) human genetic and degenerative diseases.
      Specific cell types that are affected in inherited disease can now be generated
      from easily accessible cells from the patient and compared with equivalent cells
      from healthy donors. The differences in cellular phenotype between the two may
      then be identified, and assays developed to establish therapies that prevent the
      development or progression of disease symptoms. Cellular reprogramming also has
      the potential to create new cells to replace those whose death or dysfunction
      causes disease symptoms. For patients suffering from inherited cases of
      degenerative diseases like Parkinson's disease or amyotrophic lateral sclerosis
      (also known as motor neuron disease), the future realization of such cell-based
      therapies would truly be worth its weight in gold. However, before this enormous
      potential can become a reality, several significant biological and technical
      challenges must be overcome. Furthermore, to maintain the credibility of the
      scientific community with the general public, it is important that hope-inspiring
      advances are not over-hyped. The papers in this issue of the Philosophical
      Transactions of the Royal Society B: Biological Sciences cover many areas
      relevant to this topic. In this Introduction, we provide an overall context in
      which to consider these individual papers.

PMID- 21727125
TI  - Induced pluripotent stem cells: opportunities and challenges.
AB  - Somatic cells have been reprogrammed into pluripotent stem cells by introducing a
      combination of several transcription factors, such as Oct3/4, Sox2, Klf4 and c
      Myc. Induced pluripotent stem (iPS) cells from a patient's somatic cells could be
      a useful source for drug discovery and cell transplantation therapies. However,
      most human iPS cells are made by viral vectors, such as retrovirus and
      lentivirus, which integrate the reprogramming factors into the host genomes and
      may increase the risk of tumour formation. Several non-integration methods have
      been reported to overcome the safety concern associated with the generation of
      iPS cells, such as transient expression of the reprogramming factors using
      adenovirus vectors or plasmids, and direct delivery of reprogramming proteins.
      Although these transient expression methods could avoid genomic alteration of iPS
      cells, they are inefficient. Several studies of gene expression, epigenetic
      modification and differentiation revealed the insufficient reprogramming of iPS
      cells, thus suggesting the need for improvement of the reprogramming procedure
      not only in quantity but also in quality. This report will summarize the current
      knowledge of iPS generation and discuss future reprogramming methods for medical
      application.

PMID- 21727126
TI  - The evolving biology of small molecules: controlling cell fate and identity.
AB  - Small molecules have been playing important roles in elucidating basic biology
      and treatment of a vast number of diseases for nearly a century, making their use
      in the field of stem cell biology a comparatively recent phenomenon. Nonetheless,
      the power of biology-oriented chemical design and synthesis, coupled with
      significant advances in screening technology, has enabled the discovery of a
      growing number of small molecules that have improved our understanding of stem
      cell biology and allowed us to manipulate stem cells in unprecedented ways. This
      review focuses on recent small molecule studies of (i) the key pathways governing
      stem cell homeostasis, (ii) the pluripotent stem cell niche, (iii) the directed
      differentiation of stem cells, (iv) the biology of adult stem cells, and (v)
      somatic cell reprogramming. In a very short period of time, small molecules have
      defined a perhaps universally attainable naive ground state of pluripotency, and
      are facilitating the precise, rapid and efficient differentiation of stem cells
      into somatic cell populations relevant to the clinic. Finally, following the
      publication of numerous groundbreaking studies at a pace and consistency unusual
      for a young field, we are closer than ever to completely eliminating the need for
      genetic modification in reprogramming.

PMID- 21727127
TI  - Switching on pluripotency: a perspective on the biological requirement of Nanog.
AB  - Pluripotency is a transient cellular state during early development which can be
      recreated in vitro by direct reprogramming. The molecular mechanisms driving
      entry into and exit from the pluripotent state are the subject of intense
      research interest. Here, we review the role of the homeodomain-containing
      transcription factor Nanog in mammalian embryology and induced pluripotency.
      Nanog was originally thought to be confined to the maintenance of pluripotency,
      but recent insights from genetic studies uncovered a new biological function.
      Embryonic stem cells deficient in Nanog alleles are more prone to differentiate
      but do not lose pluripotency per se. Instead, Nanog is transiently required for
      the specification of the naive pluripotent epiblast and development of primordial
      germ cells. Nanog is also essential to finalize somatic cell reprogramming during
      induction of pluripotency. We propose that this unique transcription factor acts
      as a molecular switch to turn on the naive pluripotent programme in mammalian
      cells. In this context, the capacity of Nanog to resist differentiation can be
      regarded as recapitulation of effects normally associated with the specification
      of pluripotency. Pertinent questions are how Nanog specifies naive pluripotency
      and whether this mechanism is evolutionarily conserved.

PMID- 21727128
TI  - Transcription factor heterogeneity and epiblast pluripotency.
AB  - Stem cells are defined by the simultaneous possession of the seemingly
      incongruent properties of self-renewal and multi-lineage differentiation
      potential. To maintain a stem cell population, these opposing forces must be
      balanced. Transcription factors that function to direct pluripotent cell identity
      are not all equally distributed throughout the pluripotent cell population. While
      Oct4 levels are relatively homogeneous, other transcription factors, such as
      Nanog, are more heterogeneously expressed. Moreover, Oct4 positive cells
      fluctuate between states of high Nanog expression associated with a high
      probability of self-renewal and low Nanog expression associated with an increased
      propensity to differentiate. As embryonic stem (ES) cells transit to the more
      developmentally advanced epiblast stem cell (EpiSC) state, the levels of
      pluripotency transcription factors are modulated. Such modulations are blunted in
      cells that overexpress Nanog and this may underlie the resistance of Nanog
      overexpressing cells to transit to an EpiSC state. Interestingly, increasing the
      levels of Nanog in EpiSC can facilitate reversion to the ES cell state. Together
      these observations suggest that Nanog lies close to the top of the hierarchy of
      pluripotent transcription factor regulation.

PMID- 21727129
TI  - Mapping the networks for pluripotency.
AB  - There has been an immense interest in embryonic stem cells owing to their
      pluripotent property, which refers to the ability to differentiate into all cell
      types of an embryo. In the maintenance of this pluripotent nature, transcription
      factors play essential roles, and signalling pathways also act to sustain the
      undifferentiated state. Recent studies have unravelled multiple forms of
      interconnection and crosstalk between these two regulatory aspects of
      pluripotency. With the discovery of epiblast stem cells, there is an emerging
      concept that different pluripotent states could exist, and knowledge of both
      transcriptional networks and signalling pathways has been vital in dissecting the
      properties of these different states. Similar to classical reprogramming
      methodologies, various combinations of transcription factor transduction and the
      modulation of intracellular signalling have enabled the interconversion between
      pluripotent states. These studies provide an insight into the defining
      characteristics as well as the plasticity of pluripotent cells.

PMID- 21727130
TI  - Systems biology of stem cells: three useful perspectives to help overcome the
      paradigm of linear pathways.
AB  - Stem cell behaviours, such as stabilization of the undecided state of
      pluripotency or multipotency, the priming towards a prospective fate, binary fate
      decisions and irreversible commitment, must all somehow emerge from a genome-wide
      gene-regulatory network. Its unfathomable complexity defies the standard mode of
      explanation that is deeply rooted in molecular biology thinking: the reduction of
      observables to linear deterministic molecular pathways that are tacitly taken as
      chains of causation. Such culture of proximate explanation that uses qualitative
      arguments, simple arrow-arrow schemes or metaphors persists despite the ceaseless
      accumulation of 'omics' data and the rise of systems biology that now offers
      precise conceptual tools to explain emergent cell behaviours from gene networks.
      To facilitate the embrace of the principles of physics and mathematics that
      underlie such systems and help to bridge the gap between the formal description
      of theorists and the intuition of experimental biologists, we discuss in
      qualitative terms three perspectives outside the realm of their familiar linear
      deterministic view: (i) state space (ii), high-dimensionality and (iii)
      heterogeneity. These concepts jointly offer a new vista on stem cell regulation
      that naturally explains many novel, counterintuitive observations and their
      inherent inevitability, obviating the need for ad hoc explanations of their
      existence based on natural selection. Hopefully, this expanded view will
      stimulate novel experimental designs.

PMID- 21727131
TI  - Using heterokaryons to understand pluripotency and reprogramming.
AB  - Reprogramming differentiated cells towards pluripotency can be achieved by
      different experimental strategies including the forced expression of specific
      'inducers' and nuclear transfer. While these offer unparalleled opportunities to
      generate stem cells and advance disease modelling, the relatively low levels of
      successful reprogramming achieved (1-2%) makes a direct analysis of the molecular
      events associated with productive reprogramming very challenging. The generation
      of transient heterokaryons between human differentiated cells (such as
      lymphocytes or fibroblasts) and mouse pluripotent stem cell lines results in a
      much higher frequency of successful conversion (15% SSEA4 expressing cells) and
      provides an alternative approach to study early events during reprogramming.
      Under these conditions, differentiated nuclei undergo a series of remodelling
      events before initiating human pluripotent gene expression and silencing
      differentiation-associated genes. When combined with genetic or RNAi-based
      approaches and high-throughput screens, heterokaryon studies can provide
      important new insights into the factors and mechanisms required to reprogramme
      unipotent cells towards pluripotency.

PMID- 21727132
TI  - Epigenetic reprogramming in the germline: towards the ground state of the
      epigenome.
AB  - Epigenetic reprogramming in the germline provides a developmental model to study
      the erasure of epigenetic memory as it occurs naturally in vivo in the course of
      normal embryonic development. Our data show that germline reprogramming comprises
      both active DNA demethylation and extensive chromatin remodelling that are
      mechanistically linked through the activation of the base excision DNA repair
      pathway involved in the DNA demethylation process. The observed molecular
      hallmarks of the germline reprogramming exhibit intriguing similarities to other
      dedifferentiation or regeneration systems, pointing towards the existence of
      unifying molecular pathways underlying cell fate reversal. Elucidation of
      molecular processes involved in the resetting of epigenetic information in vivo
      will thus add to our ability to manipulate cell fate and to restore pluripotency
      in in vitro settings.

PMID- 21727133
TI  - Induced pluripotent stem cells for modelling human diseases.
AB  - Research into the pathophysiological mechanisms of human disease and the
      development of targeted therapies have been hindered by a lack of predictive
      disease models that can be experimentally manipulated in vitro. This review
      describes the current state of modelling human diseases with the use of human
      induced pluripotent stem (iPS) cell lines. To date, a variety of
      neurodegenerative diseases, haematopoietic disorders, metabolic conditions and
      cardiovascular pathologies have been captured in a Petri dish through
      reprogramming of patient cells into iPS cells followed by directed
      differentiation of disease-relevant cells and tissues. However, realizing the
      true promise of iPS cells for advancing our basic understanding of disease and
      ultimately providing novel cell-based therapies will require more refined
      protocols for generating the highly specialized cells affected by disease,
      coupled with strategies for drug discovery and cell transplantation.

PMID- 21727134
TI  - Modelling familial dysautonomia in human induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells have considerable promise as a novel tool
      for modelling human disease and for drug discovery. While the generation of
      disease-specific iPS cells has become routine, realizing the potential of iPS
      cells in disease modelling poses challenges at multiple fronts. Such challenges
      include selecting a suitable disease target, directing the fate of iPS cells into
      symptom-relevant cell populations, identifying disease-related phenotypes and
      showing reversibility of such phenotypes using genetic or pharmacological
      approaches. Finally, the system needs to be scalable for use in modern drug
      discovery. Here, we will discuss these points in the context of modelling
      familial dysautonomia (FD, Riley-Day syndrome, hereditary sensory and autonomic
      neuropathy III (HSAN-III)), a rare genetic disorder in the peripheral nervous
      system. We have demonstrated three disease-specific phenotypes in FD-iPS-derived
      cells that can be partially rescued by treating cells with the plant hormone
      kinetin. Here, we will discuss how to use FD-iPS cells further in high throughput
      drug discovery assays, in modelling disease severity and in performing
      mechanistic studies aimed at understanding disease pathogenesis. FD is a rare
      disease but represents an important testing ground for exploring the potential of
      iPS cell technology in modelling and treating human disease.

PMID- 21727135
TI  - Stem cells for skeletal muscle repair.
AB  - Skeletal muscle is a highly specialized tissue composed of non-dividing, multi
      nucleated muscle fibres that contract to generate force in a controlled and
      directed manner. Skeletal muscle is formed during embryogenesis from a subset of
      muscle precursor cells, which generate both differentiated muscle fibres and
      specialized muscle-forming stem cells known as satellite cells. Satellite cells
      remain associated with muscle fibres after birth and are responsible for muscle
      growth and repair throughout life. Failure in satellite cell function can lead to
      delayed, impaired or failed recovery after muscle injury, and such failures
      become increasingly prominent in cases of progressive muscle disease and in old
      age. Recent progress in the isolation of muscle satellite cells and elucidation
      of the cellular and molecular mediators controlling their activity indicate that
      these cells represent promising therapeutic targets. Such satellite cell-based
      therapies may involve either direct cell replacement or development of drugs that
      enhance endogenous muscle repair mechanisms. Here, we discuss recent
      breakthroughs in understanding both the cell intrinsic and extrinsic regulators
      that determine the formation and function of muscle satellite cells, as well as
      promising paths forward to realizing their full therapeutic potential.

PMID- 21727136
TI  - Using stem cells to study and possibly treat type 1 diabetes.
AB  - Stem cells with the potential to form many different cell types are actively
      studied for their possible use in cell replacement therapies for several
      diseases. In addition, the differentiated derivatives of stem cells are being
      used as reagents to test for drugs that slow or correct disease phenotypes found
      in several degenerative diseases. This paper explores these approaches in the
      context of type 1 or juvenile diabetes, pointing to recent successes as well as
      the technical and theoretical challenges that lie ahead in the path to new
      treatments and cures.

PMID- 21727137
TI  - Immunological considerations for embryonic and induced pluripotent stem cell
      banking.
AB  - Recent advances in stem cell technology have generated enthusiasm for their
      potential to study and treat a diverse range of human disease. Pluripotent human
      stem cells for therapeutic use may, in principle, be obtained from two sources:
      embryonic stem cells (hESCs), which are capable of extensive self-renewal and
      expansion and have the potential to differentiate into any somatic tissue, and
      induced pluripotent stem cells (iPSCs), which are derived from differentiated
      tissue such as adult skin fibroblasts and appear to have the same properties and
      potential, but their generation is not dependent upon a source of embryos. The
      likelihood that clinical transplantation of hESC- or iPSC-derived tissues from an
      unrelated (allogeneic) donor that express foreign human leucocyte antigens (HLA)
      may undergo immunological rejection requires the formulation of strategies to
      attenuate the host immune response to transplanted tissue. In clinical practice,
      individualized iPSC tissue derived from the intended recipient offers the
      possibility of personalized stem cell therapy in which graft rejection would not
      occur, but the logistics of achieving this on a large scale are problematic owing
      to relatively inefficient reprogramming techniques and high costs. The creation
      of stem cell banks comprising HLA-typed hESCs and iPSCs is a strategy that is
      proposed to overcome the immunological barrier by providing HLA-matched
      (histocompatible) tissue for the target population. Estimates have shown that a
      stem cell bank containing around 10 highly selected cell lines with conserved
      homozygous HLA haplotypes would provide matched tissue for the majority of the UK
      population. These simulations have practical, financial, political and ethical
      implications for the establishment and design of stem cell banks incorporating
      cell lines with HLA types that are compatible with different ethnic populations
      throughout the world.

PMID- 21727138
TI  - The business of exploiting induced pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPS cells) can be exploited for both research and
      clinical applications. The first part of this review seeks to provide an
      understanding of the financial drivers and key elements of a successful business
      strategy that underpin a company focused on developing iPS-related products and
      services targeted at the research market. The latter part of the review
      highlights some of the reasons as to why the reprogramming of somatic cells is
      currently being used to develop cell-based models to screen for small molecules
      with drug-like properties rather than to develop cell-based regenerative
      medicines per se. The latter may be used to repair or replace a patient's damaged
      cells and thereby have the potential to 'cure' a disease and, in doing so,
      prevent or delay the onset of associated medical conditions. However, the cost of
      an expensive regenerative medicine and time to accrue any benefit linked to a
      decrease in co-morbidity expenditure may not outweigh the benefit for a
      healthcare community that has finite resources. The implications of this are
      discussed together with evidence that the UK National Institute for Health and
      Clinical Excellence (NICE) and the National Health Service (NHS) have established
      a precedent for a cost-sharing strategy with the pharmaceutical industry.

PMID- 21727139
TI  - StochKit2: software for discrete stochastic simulation of biochemical systems
      with events.
AB  - SUMMARY: StochKit2 is the first major upgrade of the popular StochKit stochastic
      simulation software package. StochKit2 provides highly efficient implementations
      of several variants of Gillespie's stochastic simulation algorithm (SSA), and tau
      leaping with automatic step size selection. StochKit2 features include automatic
      selection of the optimal SSA method based on model properties, event handling,
      and automatic parallelism on multicore architectures. The underlying structure of
      the code has been completely updated to provide a flexible framework for
      extending its functionality. AVAILABILITY: StochKit2 runs on Linux/Unix, Mac OS X
      and Windows. It is freely available under GPL version 3 and can be downloaded
      from http://sourceforge.net/projects/stochkit/. CONTACT:
      petzold@engineering.ucsb.edu.

PMID- 21727140
TI  - ModeRNA server: an online tool for modeling RNA 3D structures.
AB  - SUMMARY: The diverse functional roles of non-coding RNA molecules are determined
      by their underlying structure. ModeRNA server is an online tool for RNA 3D
      structure modeling by the comparative approach, based on a template RNA structure
      and a user-defined target-template sequence alignment. It offers an option to
      search for potential templates, given the target sequence. The server also
      provides tools for analyzing, editing and formatting of RNA structure files. It
      facilitates the use of the ModeRNA software and offers new options in comparison
      to the standalone program. AVAILABILITY AND IMPLEMENTATION: ModeRNA server was
      implemented using the Python language and the Django web framework. It is freely
      available at http://iimcb.genesilico.pl/modernaserver. CONTACT:
      iamb@genesilico.pl.

PMID- 21727141
TI  - Simple Neurite Tracer: open source software for reconstruction, visualization and
      analysis of neuronal processes.
AB  - MOTIVATION: Advances in techniques to sparsely label neurons unlock the potential
      to reconstruct connectivity from 3D image stacks acquired by light microscopy. We
      present an application for semi-automated tracing of neurons to quickly annotate
      noisy datasets and construct complex neuronal topologies, which we call the
      Simple Neurite Tracer. AVAILABILITY: Simple Neurite Tracer is open source
      software, licensed under the GNU General Public Licence (GPL) and based on the
      public domain image processing software ImageJ. The software and further
      documentation are available via http://fiji.sc/Simple_Neurite_Tracer as part of
      the package Fiji, and can be used on Windows, Mac OS and Linux. Documentation and
      introductory screencasts are available at the same URL. CONTACT:
      longair@ini.phys.ethz.ch; longair@ini.phys.ethz.ch.

PMID- 21727142
TI  - The history of female genital tract malformation classifications and proposal of
      an updated system.
AB  - BACKGROUND: A correct classification of malformations of the female genital tract
      is essential to prevent unnecessary and inadequate surgical operations and to
      compare reproductive results. An ideal classification system should be based on
      aetiopathogenesis and should suggest the appropriate therapeutic strategy.
      METHODS: We conducted a systematic review of relevant articles found in PubMed,
      Scopus, Scirus and ISI webknowledge, and analysis of historical collections of
      'female genital malformations' and 'classifications'. Of 124 full-text articles
      assessed for eligibility, 64 were included because they contained original
      general, partial or modified classifications. RESULTS: All the existing
      classifications were analysed and grouped. The unification of terms and concepts
      was also analysed. Traditionally, malformations of the female genital tract have
      been catalogued and classified as Mullerian malformations due to agenesis, lack
      of fusion, the absence of resorption and lack of posterior development of the
      Mullerian ducts. The American Fertility Society classification of the late 1980s
      included seven basic groups of malformations also considering the Mullerian
      development and the relationship of the malformations to fertility. Other
      classifications are based on different aspects: functional, defects in vertical
      fusion, embryological or anatomical (Vagina, Cervix, Uterus, Adnex and Associated
      Malformation: VCUAM classification). However, an embryological-clinical
      classification system seems to be the most appropriate. CONCLUSIONS: Accepting
      the need for a new classification system of genitourinary malformations that
      considers the experience gained from the application of the current
      classification systems, the aetiopathogenesis and that also suggests the
      appropriate treatment, we proposed an update of our embryological-clinical
      classification as a new system with six groups of female genitourinary anomalies.

PMID- 21727143
TI  - Treatment of refractory chronic cluster headache by chronic occipital nerve
      stimulation.
AB  - BACKGROUND: Greater occipital nerve stimulation (ONS) has been recently proposed
      to treat severe chronic cluster headache patients (CCH) refractory to medical
      treatment. We report the results of a French multidisciplinary cohort study.
      METHODS: Thirteen CCH patients were operated and data were collected
      prospectively. All of them suffered from CCH according to the International
      Headache Society classification, lasting for more than 2 years, refractory to
      pharmacological prophylactic treatment with adequate trials, with at least one
      daily attack. Chronic ONS was delivered through a subcutaneous occipital
      electrode connected to an implanted generator, in order to induce paraesthesias
      perceived locally in the lower occipital region. RESULTS: After surgery (mean
      follow-up 14,6 months), the mean attack frequency and intensity decreased by 68%
      and 49%, respectively. At last follow-up, 10/13 patients were considered as
      responders (improvement >50%). Prophylactic treatment could be stopped or reduced
      in 8/13 cases. Local infection occurred in one patient, leading to hardware
      removal. CONCLUSIONS: Our data confirmed the results of the 36 similar cases
      reported in the literature, suggesting that ONS may act as a prophylactic
      treatment in chronic CH. Considering their respective risks, ONS should be
      proposed before deep brain stimulation in severe refractory CCH patients.

PMID- 21727144
TI  - Ketogenic diet in migraine treatment: a brief but ancient history.

PMID- 21727145
TI  - Perceptual illusions provide clues to excitatory: inhibitory balance in migraine
      neocortex.

PMID- 21727146
TI  - Post-ban self-reports on economic impact of smoke-free bars and restaurants are
      biased by pre-ban attitudes. A longitudinal study among employees.
AB  - INTRODUCTION: Objective sales data have indicated that the Norwegian indoor smoke
      free regime implemented in June 2004 did not affect the hospitality business
      negatively. This paper investigates whether self-reports on the economic impact
      of the smoking ban from employees in the hospitality sector gave similar results,
      and whether post-ban self-reports on the economic impact of the ban were
      influenced by pre-ban attitudes towards smoke-free policies. METHODS: A random
      sample of 516 employees in bars and restaurants stated their attitudes towards
      smoke-free policies shortly before the ban became effective. One year later, the
      same respondents gave their perceptions of changes in patronage for their
      workplace. Data were collected using self-administered questionnaires and
      telephone interviews. RESULTS: 56.4% of the hospitality workers stated that the
      ban on smoking had led to a large reduction (28.2%) or some reduction (28.2%) in
      the number of patrons, a result inconsistent with analysis of sales data. After
      adjusting for demographic and smoking-related variables, a negative pre-ban
      attitude significantly increased the odds for reporting a negative economic
      impact post ban (odds ratio 2.48, confidence interval 1.48-4.14). CONCLUSIONS:
      Subjective reports of the economic impact from an indoor ban on smoking are
      influenced by attitudes towards smoke-free policies and should not be considered
      as a valid measure of the economic effect.

PMID- 21727147
TI  - Lack of support structures in prioritization decision making concerning patients
      and resources. Interviews with Swedish physicians.
AB  - AIM: To investigate physicians' experiences in relation to prioritization and
      financing in health care in order to gain a deeper understanding of the reasons
      behind their standpoints. METHODS: Eighteen physicians, seven women and eleven
      men, aged 30 to 69 years were interviewed and the text was analyzed using an
      inductive approach, also described as conventional qualitative content analysis.
      RESULTS: Experience of setting healthcare priorities and difficult decision
      making differed widely among the physicians and seemed to be related to the
      number of years in professional practice. Their view of how resources should be
      allocated between disciplines/patients showed that they wanted politicians to
      make the decisions, with support from medical professions. The overwhelming
      impression of their reasoning showed that they lacked support structures for
      their decision making and could be understood under the following categories:
      prioritisation, easier in theory than in practice, and increasing costs threaten
      the Swedish welfare model. CONCLUSIONS: The findings of this study highlight the
      importance of practical national guidelines concerning vertical prioritization,
      also as an important measure to make prioritization more distinct and
      transparent. The physicians further had a need for tools to increase patients'
      awareness of their health. The findings of this study also showed that an
      awareness of the actual costs involved might increase the responsibility among
      both physicians and patients. The physicians' lack of support structures implies
      an urgent need for practical national guidelines, especially concerning vertical
      prioritization. This will also make prioritization appear clear and transparent
      for citizens.

PMID- 21727148
TI  - Oral fingolimod (FTY720) in relapsing multiple sclerosis: impact on health
      related quality of life in a phase II study.
AB  - BACKGROUND: Health-related quality of life (HRQoL) worsens with multiple
      sclerosis (MS) relapses and disease progression. Common symptoms including
      depression and fatigue may contribute to poor HRQoL. OBJECTIVES: To report
      exploratory analyses assessing the impact of fingolimod (FTY720) on HRQoL and
      depression in a phase II study of relapsing MS. METHODS: The Hamburg Quality of
      Life Questionnaire in MS (HAQUAMS) and Beck Depression Inventory second edition
      (BDI-II) scores were assessed during a 6-month, placebo-controlled study and
      optional extension. RESULTS: HAQUAMS total score improved with fingolimod and
      worsened with placebo. Mean score change from baseline to month 6 was -0.02 with
      fingolimod 1.25 mg (p < 0.05 versus placebo), -0.01 with fingolimod 5.0 mg and +
      0.12 with placebo. Categorical data supported a clinically important effect of
      fingolimod on HRQoL. Fingolimod 1.25 mg was also beneficial over placebo in the
      fatigue/thinking HAQUAMS sub-domain (p < 0.05 versus placebo). Change in mean BDI
      II scores from baseline to month 6 and the proportion of patients with BDI-II
      scores indicative of clinical depression favored fingolimod 1.25 mg over placebo
      (p < 0.05 for both). At month 4, mean BDI-II and HAQUAMS total scores appeared to
      be maintained in fingolimod-treated patients. CONCLUSION: Fingolimod 1.25 mg may
      improve HRQoL and depression at 6 months compared with placebo in patients with
      relapsing MS.

PMID- 21727149
TI  - Best practices for the nonpharmacological treatment of depression at the end of
      life.
AB  - This literature review summarizes the current research on nonpharmacological
      management of depressive symptoms for patients nearing the end of their lives.
      Research suggests that major depressive disorder may affect terminally ill adults
      at a disproportionately high rate. Psychotherapy has not been shown to have
      consistent benefits among patients in the final months of life. Semi
      psychotherapeutic (life review) techniques are likely most effective in patients
      in the final weeks of life. Non-psychotherapeutic techniques such as hypnotherapy
      have not been studied sufficiently to be recommended as first-line treatments.
      Based on the current research, it is our recommendation that psychotherapy be
      used first-line in patients with approximately 6 months or more to live, and that
      semi-psychotherapeutic techniques be first-line in patients with 6 months or less
      to live.

PMID- 21727150
TI  - Improving cultural competency among hospice and palliative care volunteers:
      recommendations for social policy.
AB  - This case study of 14 hospice and palliative care volunteers looked for
      recommendations and suggestions on how to increase cultural competency among
      hospice volunteers. In-depth interviews were conducted with a hospice in Toronto,
      Canada, and findings reveal that volunteers have very specific and diverse
      recommendations on how they prefer to be briefed and educated on cultural
      competency issues surrounding their patients. Findings also reveal hospice
      volunteers want more cultural competency training and acknowledge the importance
      of being culturally competent. This article concludes with a precis on
      recommendations for increasing cultural competency in hospice and palliative care
      for both volunteers and agencies and discusses the top 4 future trends in
      cultural competency for hospice care.

PMID- 21727151
TI  - Usefulness of the 6-minute walk test and the 200-metre fast walk test to
      individualize high intensity interval and continuous exercise training in
      coronary artery disease patients after acute coronary syndrome: a pilot
      controlled clinical study.
AB  - OBJECTIVE: To study the effects of three individualized exercise training
      prescriptions using either a percentage of maximal heart rate (HR), maximal 6
      minute walk test (6MWT) HR, or maximal 200-metre fast walk test (200-mFWT) HR, on
      walking performance and exercise capacity in coronary artery disease (CAD)
      patients. DESIGN: Controlled clinical study. PARTICIPANTS: Twenty-seven
      outpatients enrolled in a rehabilitation programme after an acute coronary
      syndrome. SETTING: Cardiac rehabilitation unit. INTERVENTIONS: Three groups: (A):
      moderate intensity continuous exercise (MICE) at 70% of the maximal HR of the
      graded maximal exercise test (n = 10); (B): MICE at the maximal 6MWT HR (n = 8);
      (C): high intensity interval training (HIIT) based on the 6MWT and the 200-mFWT
      maximal HR (n = 9). Group B and C performed walk tests every 2 weeks, to readjust
      training HR (THR) if needed. MEASURES: 6MWT and 200-mFWT performances, peak VO(2)
      and peak power (Pmax). RESULTS: 6MWT and 200-mFWT performances improved
      significantly and similarly in all groups (P < 0.05). Peak VO(2) improved
      significantly in all groups (P < 0.05), this improvement being higher in group C
      (HIIT) versus A (P < 0.05). Group B was closer to the recommended THR during
      exercise sessions compared to group A. CONCLUSION: This pilot study showed that
      using the 6MWT and 200-mFWT HR to individualize MICE or HIIT prescription is
      feasible in CAD patients, and could lead them closer to THR objective, to similar
      improvements in walking performance, and greater peak VO(2) increase for HIIT.
      Future randomised studies should investigate long-term effects of programmes
      prescribed from walk tests HR, especially for HIIT modality.

PMID- 21727152
TI  - Nationwide quality improvement of cholecystectomy: results from a national
      database.
AB  - OBJECTIVE: To evaluate whether quality improvements in the performance of
      cholecystectomy have been achieved in Denmark since 2006, after revision of the
      Danish National Guidelines for treatment of gallstones. DESIGN: A national
      database that monitors the quality of cholecystectomy was established, and
      registration of all cholecystectomies in Denmark was mandatory since 1 January
      2006. Indicators describing the operation, the postoperative course, the surgical
      outcome and various risk factors were followed for 4 years. RESULTS: from 2006
      were defined as reference values and indicator values, and covariates were
      stratified by year and tested for trend. Logistic regression models were used to
      adjust for changes in the prevalence of risk factors/covariates in the study
      period. SETTING: Nationwide, prospective clinical database in Denmark. Data from
      2006 to 2009. PARTICIPANTS: 23,672 patients undergoing cholecystectomy where a
      laparoscopic procedure was considered the standard operation according to
      national guidelines. MAIN OUTCOME MEASURES: The rate of conversion from
      laparoscopic to open operation, the frequency of primary open operations where
      laparoscopic procedure was the standard, length of postoperative stay including
      frequency of same-day surgery, additional surgical procedures within 30 days,
      readmission and mortality. Results Conversion rate and frequency of primary open
      cholecystectomy were reduced in the study period. Same-day surgery increased by
      14.6%, without an increase in readmission rate (9.4%). The frequency of
      'additional procedures within 30 days' was also reduced (2.8%). The frequency of
      injuries requiring reconstructive bile-duct surgery was unaffected (0.15%).
      CONCLUSION: The study demonstrates nationwide quality improvements of
      cholecystectomy in Denmark from 2006 to 2009.

PMID- 21727153
TI  - Prolonged exposure to GH impairs insulin signaling in the heart.
AB  - Acromegaly is associated with cardiac hypertrophy, which is believed to be a
      direct consequence of chronically elevated GH and IGF1. Given that insulin is
      important for cardiac growth and function, and considering that GH excess induces
      hyperinsulinemia, insulin resistance, and cardiac alterations, it is of interest
      to study insulin sensitivity in this tissue under chronic conditions of elevated
      GH. Transgenic mice overexpressing GH present cardiomegaly and perivascular and
      interstitial fibrosis in the heart. Mice received an insulin injection, the heart
      was removed after 2  min, and immunoblotting assays of tissue extracts were
      performed to evaluate the activation and abundance of insulin-signaling
      mediators. Insulin-induced tyrosine phosphorylation of the insulin receptor (IR)
      was conserved in transgenic mice, but the phosphorylation of IR substrate 1
      (IRS1), its association with the regulatory subunit of the phosphatidylinositol 3
      kinase (PI3K), and the phosphorylation of AKT were decreased. In addition, total
      content of the glucose transporter GLUT4 was reduced in transgenic mice. Insulin
      failed to induce the phosphorylation of the mammalian target of rapamycin (mTOR).
      However, transgenic mice displayed increased basal activation of the
      IR/IRS1/PI3K/AKT/mTOR and p38 signaling pathways along with higher serine
      phosphorylation of IRS1, which is recognized as an inhibitory modification. We
      conclude that GH-overexpressing mice exhibit basal activation of insulin
      signaling but decreased sensitivity to acute insulin stimulation at several
      signaling steps downstream of the IR in the heart. These alterations may be
      associated with the cardiac pathology observed in these animals.

PMID- 21727154
TI  - Correlates of HIV testing among abused women in South Africa.
AB  - Gender-based violence increases a woman's risk for HIV but little is known about
      her decision to get tested. We interviewed 97 women seeking abuse-related
      services from a nongovernmental organization (NGO) in Johannesburg, South Africa.
      Forty-six women (47%) had been tested for HIV. Caring for children (odds ratio
      [OR] = 0.27, 95% confidence interval [CI] = [0.07, 1.00]) and conversing with
      partner about HIV (OR = 0.13, 95% CI = [0.02, 0.85]) decreased odds of testing.
      Stronger risk-reduction intentions (OR = 1.27, 95% CI = [1.01, 1.60]) and seeking
      help from police (OR = 5.51, 95% CI = [1.18, 25.76]) increased odds of testing.
      Providing safe access to integrated services and testing may increase testing in
      this population. Infection with HIV is highly prevalent in South Africa where an
      estimated 16.2% of adults between the ages of 15 and 49 have the virus. The
      necessary first step to stemming the spread of HIV and receiving life-saving
      treatment is learning one's HIV serostatus through testing. Many factors may
      contribute to someone's risk of HIV infection and many barriers may prevent
      testing. One factor that does both is gender-based violence.

PMID- 21727155
TI  - The cumulative impact of sexual revictimization on emotion regulation
      difficulties: an examination of female inmates.
AB  - The present study examined associations between child sexual abuse (CSA), adult
      sexual victimization, and emotion regulation difficulties in a sample of 168
      incarcerated women. Approximately 50% of the participants reported CSA, 54%
      reported adult sexual victimization, and 38% reported sexual revictimization
      (i.e., CSA and adult victimization). Revictimized women reported significantly
      greater difficulties with several facets of emotion regulation when compared to
      singly victimized and nonvictimized women. Interestingly, singly victimized women
      did not demonstrate greater emotion regulation deficits when compared to
      nonvictims. Findings suggest that the negative impact of victimization
      experiences on adult emotion regulation abilities may be cumulative. Furthermore,
      they highlight the potential importance of assessing and targeting emotion
      regulation difficulties among child abuse and adult sexual victimization
      survivors.

PMID- 21727156
TI  - Static foot disorders: a major risk factor for chronic venous disease?
AB  - OBJECTIVE: To study the relationship between the static foot disorders (SFDs) and
      chronic venous disease (CVD). MATERIAL AND METHODS: A retrospective study of 824
      feet in unselected 412 patients seen by one phlebologist using a standardized
      record form. A complete clinical, aetiological, anatomical and pathological
      elements (CEAP) classification was determined. Alleged venous symptoms were
      recorded using a 10-point visual analogue scale and scored using a customized
      questionnaire. A standardized measurement of the Djian-Annonier angle was used to
      quantify and identify the presence of any static disorder of the foot. RESULTS:
      There were 156 men (37.8%) and 256 women (62.2%) who were included in this study.
      A majority of patients (59.3%) had a CEAP classification of C3 or greater. Static
      disorders of the feet were found to be very common in the study population: 137
      feet were hollow feet (16.6%) and 120 flat feet (14.5%). Thus, 31% of all of the
      feet had some form of SFD. A significant correlation was found between the
      incidence of SFD and body mass index (P < 0.01), the presence of symptoms
      (P<0.001) and prolonged standing during the day (>5 hours, P < 0.05). The
      severity of the CVD, represented by the CEAP clinical classes, was also found to
      be very significantly related to the SFD (P < 0.001). This correlation was found
      to be independent of age. CONCLUSION: Static disorders of the foot can be
      considered as an important risk factor that negatively affects CVD. In daily
      practice, it is often underestimated. This emphasizes the crucial importance of
      the detection of SFD during the clinical exam of all CVD patients. Correction of
      static disorders of the feet will improve symptoms due to the SFD, as well as
      those related to venous stasis. These results can easily be explained by
      improvement of foot pump efficacy during walking.

PMID- 21727157
TI  - Bringing in the target audience in bystander social marketing materials for
      communities: suggestions for practitioners.
AB  - The Know Your PowerTM social marketing campaign images model active bystander
      behaviors that target audience members can use in situations where sexual and
      relationship violence and stalking are occurring, have occurred, or have the
      potential to occur. In this practitioner note, we describe strategies that we
      have used to engage target audience members in the development of the social
      marketing campaign that we hope can be used by practitioners. We give examples
      from the development and evaluation of the Know Your Power(TM) social marketing
      campaign that used focus group and other types of feedback from the target
      audience to inform the direction of the campaign.

PMID- 21727159
TI  - Stillbirth and neonatal mortality in monochorionic and dichorionic twins: a
      population-based study.
AB  - BACKGROUND: Chorionicity is one of the main predictors of higher perinatal
      mortality in twins. The aim of this large population-based study was to analyse
      stillbirth and neonatal mortality by cause of death and chorionicity and to
      quantify the risk of stillbirth by gestational age in dichorionic (DC) and
      monochorionic (MC) twins. METHODS: We used data on twin maternities delivered in
      the North of England from 1998 to 2007 and notified to the Northern Survey of
      Twin and Multiple Pregnancy. Prospective risk of stillbirth by gestational age at
      death was calculated using number of stillborn fetuses at or beyond a given
      gestational period per 1000 fetuses in ongoing pregnancies. RESULTS: There were
      4565 twin maternities (9130 twins) with an overall twinning rate of 14.9 per 1000
      maternities. The overall stillbirth and neonatal mortality rates in twins during
      1998-2007 were 18.0/1000 births and 23.0/1000 live births, respectively.
      Stillbirth and neonatal mortality rates were significantly higher in MC than DC
      twins: 44.4 versus 12.2 per 1000 births [relative risk (RR): 3.6; 95% CI: 2.6
      5.1], and 32.4 versus 21.4 per 1000 live births (RR: 1.5; 95% CI: 1.04-2.2),
      respectively. There was no significant improvement over time in either stillbirth
      or neonatal mortality rates in either group. The prospective risk of antepartum
      stillbirth was higher for MC than DC twins at all preterm gestations and the
      highest risk was before 28 weeks' gestation. CONCLUSIONS: MC twins have higher
      rates of stillbirth and neonatal mortality than DC twins, and rates did not
      improve over 1998-2007. The prospective risk of antepartum stillbirth is much
      higher for MC twins at all gestational ages.

PMID- 21727160
TI  - The impact of shame and self-judgment on psychopathology in infertile patients.
AB  - BACKGROUND: Little is known about psychological processes of infertile couples
      pursuing medical treatment in comparison with fertile couples and adoption
      candidates who also suffer from infertility but are not seeking medical help.
      This study aims to contribute to a better understanding of these individuals in
      terms of psychological processes (such as external shame, internal shame and self
      judgment) and their association with psychopathology, also attending to gender
      differences. METHODS: One hundred control couples without known fertility
      problems [fertile group (FG)], 100 couples with an infertility diagnosis and
      pursuing medical treatment [infertile group (IG)], and 40 couples with an
      infertility diagnosis who are applying for adoption [adoption group (AG)]
      completed the instruments: Beck Depression Inventory, Spielberger State-Trait
      Anxiety Inventory, Others as Shamer, Experience of Shame Scale and the Self
      compassion Scale. One-way analysis of variances were used to compare the three
      groups demographic and study variables. Pearson correlations and linear multiple
      regression analysis were performed to investigate the associations between shame,
      self-judgment, depression and anxiety. To explore gender differences, T-tests
      were used. RESULTS: The IG group scored higher than FG and AG in measures of
      depression, anxiety, external shame, internal shame and self-judgment. In
      infertile couples, self-judgment, external shame and internal shame emerged as
      significant predictors of depressive symptomatology. Women with an infertility
      diagnosis tend to present higher levels of depressive and anxiety symptoms in
      comparison with fertile controls and adoption candidates. CONCLUSIONS: This study
      highlights the importance of emotional regulation processes such as internal and
      external shame, and self-judgment, to the understanding of psychopathological
      symptomatology associated with infertility. Our results suggest that these issues
      should be addressed in a therapeutic context with these couples. Nevertheless,
      the heterogeneity of the infertile group, in what concerns different stages of
      medical diagnosis and treatment, might represent a limitation in the
      interpretation of our findings.

PMID- 21727161
TI  - Does gender moderate the relationship between childhood maltreatment and adult
      depression?
AB  - Although considerable evidence demonstrates that adults who report childhood
      maltreatment are at increased risk of depression in adulthood, little is known
      about whether gender moderates risk. In a sample of 5,673 adult Health
      Maintenance Organization (HMO) patients, the authors employed the Patient Health
      Questionnaire-8 (PHQ-8) to assess major depressive disorder (MDD) and the
      Childhood Trauma Questionnaire (CTQ) to assess five different types of childhood
      maltreatment: emotional, physical, and sexual abuse, as well as emotional and
      physical neglect. Logistic regression models tested the main and interactive
      effects of gender and childhood maltreatment. Consistent with previous studies,
      men and women with histories of each type of childhood adversity were
      significantly more likely to meet criteria for MDD. However, the authors found no
      evidence that gender moderates the risk of depression. These findings suggest
      that men and women reporting history of childhood maltreatment are equally likely
      to suffer major depression in adulthood.

PMID- 21727162
TI  - Infection with polyomavirus JC.

PMID- 21727163
TI  - Interpreting and reporting clinical trials with results of borderline
      significance.

PMID- 21727164
TI  - Otitis media with effusion ("glue ear").

PMID- 21727165
TI  - Commercial sector has much to offer in improving health, says England's chief
      medical officer.

PMID- 21727166
TI  - NSAIDs and atrial fibrillation.

PMID- 21727167
TI  - Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or
      flutter: population based case-control study.
AB  - OBJECTIVES: To examine the risk of atrial fibrillation or flutter associated with
      use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or selective
      cyclo-oxygenase (COX) 2 inhibitors. DESIGN: Population based case-control study
      using data from medical databases. SETTING: Northern Denmark (population 1.7
      million). PARTICIPANTS: 32 602 patients with a first inpatient or outpatient
      hospital diagnosis of atrial fibrillation or flutter between 1999 and 2008; 325
      918 age matched and sex matched controls based on risk-set sampling. MAIN OUTCOME
      MEASURES: Exposure to NSAID use at the time of admission (current use) or before
      (recent use). Current use was further classified as new use (first ever
      prescription redemption within 60 days before diagnosis date) or long term use.
      We used conditional logistic regression to compute odds ratios as unbiased
      estimates of the incidence rate ratios. RESULTS: 2925 cases (9%) and 21 871
      controls (7%) were current users of either non-selective NSAIDs or COX 2
      inhibitors. Compared with no use, the incidence rate ratio associating current
      drug use with atrial fibrillation or flutter was 1.33 (95% confidence interval
      1.26 to 1.41) for non-selective NSAIDs and 1.50 (1.42 to 1.59) for COX 2
      inhibitors. Adjustments for age, sex, and risk factors for atrial fibrillation or
      flutter reduced the incidence rate ratio to 1.17 (1.10 to 1.24) for non-selective
      NSAIDs and 1.27 (1.20 to 1.34) for COX 2 inhibitors. Among new users, the
      adjusted incidence rate ratio was 1.46 (1.33 to 1.62) for non-selective NSAIDs
      and 1.71 (1.56 to 1.88) for COX 2 inhibitors. Results for individual NSAIDs were
      similar. CONCLUSIONS: Use of non-aspirin NSAIDs was associated with an increased
      risk of atrial fibrillation or flutter. Compared with non-users, the association
      was strongest for new users, with a 40-70% increase in relative risk (lowest for
      non-selective NSAIDs and highest for COX 2 inhibitors). Our study thus adds
      evidence that atrial fibrillation or flutter needs to be added to the
      cardiovascular risks to be considered when prescribing NSAIDs.

PMID- 21727168
TI  - The association between venous thromboembolism and physical inactivity in
      everyday life.

PMID- 21727169
TI  - Physical inactivity and idiopathic pulmonary embolism in women: prospective
      study.
AB  - OBJECTIVES: To determine the association between physical inactivity (that is, a
      sedentary lifestyle) and incident idiopathic pulmonary embolism. DESIGN:
      Prospective cohort study. SETTING: Nurses' Health Study. PARTICIPANTS: 69 950
      female nurses who completed biennial questionnaires from 1990 to 2008. Main
      outcome measures The primary outcome was idiopathic pulmonary embolism confirmed
      in medical records. Multivariable Cox proportional hazards models controlled for
      age, body mass index (BMI), energy intake, smoking, pack years, race, spouse's
      educational attainment, parity, menopause, non-aspirin non-steroidal anti
      inflammatory drugs, warfarin, multivitamin supplements, hypertension, coronary
      heart disease, rheumatological disease, and dietary patterns. The primary
      exposure was physical inactivity, measured in hours of sitting each day. The
      secondary exposure was physical activity, measured in metabolic equivalents a
      day. RESULTS: Over the 18 year study period, there were 268 cases of incident
      idiopathic pulmonary embolism. There was an association between time of sitting
      and risk of idiopathic pulmonary embolism (41/104 720 v 16/14 565 cases in most
      inactive v least inactive in combined data; P<0.001 for trend). The risk of
      pulmonary embolism was more than twofold in women who spent the most time sitting
      compared with those who spent the least time sitting (multivariable hazard ratio
      2.34, 95% confidence interval 1.30 to 4.20). There was no association between
      physical activity and pulmonary embolism (P=0.53 for trend). CONCLUSIONS:
      Physical inactivity is associated with incident pulmonary embolism in women.
      Interventions that decrease time sitting could lower the risk of pulmonary
      embolism.

PMID- 21727170
TI  - Russia declares "total war" on the country's drug problem.

PMID- 21727172
TI  - Obama administration wins first appeal court ruling on health reform.

PMID- 21727173
TI  - Per patient funding would end inequalities in palliative care provision, says
      review.

PMID- 21727176
TI  - Politics, primary healthcare and health: was Virchow right?

PMID- 21727175
TI  - Comparison of the use of minimized cardiopulmonary bypass with conventional
      techniques on the incidence of retinal microemboli during aortic valve
      replacement surgery.
AB  - OBJECTIVES: Minimized cardiopulmonary bypass (MCPB) circuits have been shown to
      reduce cerebral and retinal microembolisation during coronary artery bypass graft
      (CABG) surgery compared to conventional CPB (CCPB) circuits. Our aim was to
      evaluate whether the reduction of microembolisation is sustained in aortic valve
      surgery, as well as to evaluate the effects of MCPB on inflammatory, endothelial,
      and platelet activation markers. MATERIAL AND METHODS: Patients were randomized
      to undergo aortic valve replacement (AVR), with or without CABG, with MPCB (n=20)
      or CCPB (n=20). After anaesthesia induction and termination of CPB, standardized
      digital retinal fluorescein angiography images were obtained on both eyes and
      analyzed in a blinded fashion. Blood samples were collected at eight time points
      until the third postoperative day. RESULTS: Fewer patients in the MCPB group
      showed evidence of microembolic perfusion defects on postperfusion retinal
      fluorescein angiographs compared to the CCPB group (37% vs. 63%, absolute
      difference 26%, 95% CI -5% -51%, P = 0.194). Polymorphonuclear leukocyte (PMN)
      elastase and von Willebrand factor release were statistically significantly
      reduced in the MCPB group, but there were no significant differences in other
      markers of inflammation, coagulation or endothelial activation. A significantly
      higher three-fold increase in the amount of shed blood was collected to the cell
      saver with a higher rate of intraoperative platelet transfusion in the MCPB group
      compared to CCPB. CONCLUSIONS: The use of MCPB was associated statistically
      insignificantly with less retinal microemboli compared to CCPB. MCPB was
      complicated by excess bleeding and need for transfusion. The feasibility of MCPB
      techniques in valve surgery requires further studies.

PMID- 21727177
TI  - Excessive amounts of mu heavy chain block B-cell development.
AB  - Antigen-independent B-cell development occurs in several stages that depend on
      the expression of Ig heavy and light chain. We identified a line of mice that
      lacked mature B cells in the spleen. This mouse line carried approximately 11
      copies of a transgene of the murine heavy chain constant region locus, and B
      lineage cells expressed excessive amounts of the intracellular MU heavy chain. B
      cell development failed in the bone marrow at the pro/pre B-cell transition, and
      examination of other lines with various copy numbers of the same transgene
      suggested that deficiencies in B-cell development increased with increased
      transgene copy number. Expression of a transgenic (Tg) light chain along with the
      Tg MU heavy chain led to minimal rescue of B-cell development in the bone marrow
      and B cells in the spleen. There are several potential mechanisms for the death
      of pro/pre B cells as a consequence of excess heavy chain expression.

PMID- 21727178
TI  - From host immunity to pathogen invasion: the effects of helminth coinfection on
      the dynamics of microparasites.
AB  - Concurrent infections with multiple parasites are ubiquitous in nature.
      Coinfecting parasites can interact with one another in a variety of ways,
      including through the host's immune system via mechanisms such as immune trade
      offs and immunosuppression. These within-host immune processes mediating
      interactions among parasites have been described in detail, but how they scale up
      to determine disease dynamic patterns at the population level is only beginning
      to be explored. In this review, we use helminth-microparasite coinfection as a
      model for examining how within-host immunological effects may influence the
      ecological outcome of microparasitic diseases, with a specific focus on disease
      invasion. The current literature on coinfection between helminths and major
      microparasitic diseases includes many studies documenting the effects of
      helminths on individual host responses to microparasites. In many cases, the
      observed host responses map directly onto parameters relevant for quantifying
      disease dynamics; however, there have been few attempts at integrating data on
      individual-level effects into theoretical models to extrapolate from the
      individual to the population level. Moreover, there is considerable variability
      in the particular combination of disease parameters affected by helminths across
      different microparasite systems. We develop a conceptual framework identifying
      some potential sources of such variability: Pathogen persistence and severity,
      and resource availability to hosts. We also generate testable hypotheses
      regarding diseases and the environmental contexts when the effects of helminths
      on microparasite dynamics should be most pronounced. Finally, we use a case study
      of helminth and mycobacterial coinfection in the African buffalo to illustrate
      both progress and challenges in understanding the population-level consequences
      of within-host immunological interactions, and conclude with suggestions for
      future research that will help improve our understanding of the effects of
      coinfection on dynamics of infectious diseases.

PMID- 21727179
TI  - A review of self-medication in physicians and medical students.
AB  - BACKGROUND: There is a culture within medicine that doctors do not expect
      themselves or their colleagues to be sick. Thus, the associated complexities of
      self-diagnosis, self-referral and self-treatment among physicians are significant
      and may have repercussions for both their own health and, by implication, for the
      quality of care delivered to patients. AIMS: To collate what is known about the
      self-treatment behaviour of physicians and medical students. METHODS: The
      following databases were searched: PubMed, PsychInfo, EBSCO, Medline, BioMed
      central and Science Direct. Inclusion criteria specified research assessing self
      treatment and self-medicating of prescription drugs among physicians and/or
      medical students. Only peer-reviewed English language empirical studies published
      between 1990 and 2009 were included. RESULTS: Twenty-seven studies were
      identified that fitted the inclusion criteria. Self-treatment and self-medicating
      was found to be a significant issue for both physicians and medical students. In
      76% of studies, reported self-treatment was >50% (range: 12-99%). Overall, only
      one of two respondents was registered with a general practitioner or primary care
      physician (mean = 56%, range = 21-96). Deeper analysis of studies revealed that
      physicians believed it was appropriate to self-treat both acute and chronic
      conditions and that informal care paths were common within the medical
      profession. CONCLUSIONS: Self-treatment is strongly embedded within the culture
      of both physicians and medical students as an accepted way to enhance/buffer work
      performance. The authors believe that these complex self-directed care behaviours
      could be regarded as an occupational hazard for the medical profession.

PMID- 21727180
TI  - Systematic review: occupational physical activity and low back pain.
AB  - BACKGROUND: Although various occupational physical activities are suspected of
      contributing to low back pain (LBP), causal relationships have not been
      confirmed, complicating adjudication of work injuries, return to work
      instructions and preventive efforts. AIMS: To summarize eight systematic review
      (SR) reports that examined evidence supporting causal relationships between
      bending/twisting, awkward postures, sitting, standing/walking, carrying,
      pushing/pulling, lifting and manual handling/assisting patients and LBP. METHODS:
      A literature search was conducted to identify eligible studies. Methodological
      quality was assessed using a modified Newcastle-Ottawa Scale (NOS). Levels of
      evidence supporting factors for causation were examined using a Bradford Hill
      framework. Results were presented in eight SR reports, each focused on one or
      more related physical activities. This study summarizes findings from those
      reports and offers clinicians an overview. RESULTS: Collectively, the eight SR
      reports included 99 studies. None found strong evidence supporting a causal
      relationship between any occupational physical activity considered and LBP.
      Conflicting evidence was found between LBP and bending, twisting, lifting or
      pushing/pulling, but only for statistical association, not causation. Strong
      evidence against a causal relationship was found between LBP and manual
      handling/assisting patients, awkward postures, carrying, sitting, standing or
      walking. CONCLUSIONS: Although occupational physical activities are suspected of
      causing LBP, findings from the eight SR reports did not support this hypothesis.
      This may be related to insufficient or poor quality scientific literature, as
      well as the difficulty of establishing causation of LBP. These population-level
      findings do not preclude the possibility that individuals may attribute their LBP
      to specific occupational physical activities.

PMID- 21727181
TI  - Methyl jasmonate induces ATP biosynthesis deficiency and accumulation of proteins
      related to secondary metabolism in Catharanthus roseus (L.) G. hairy roots.
AB  - Jasmonates are specific signal molecules in plants that are involved in a diverse
      set of physiological and developmental processes. However, methyl jasmonate
      (MeJA) has been shown to have a negative effect on root growth and, so far, the
      biochemical mechanism for this is unknown. Using Catharanthus roseus hairy roots,
      we were able to observe the effect of MeJA on growth inhibition, cell
      disorganization and cell death of the root cap. Hairy roots treated with MeJA
      induced the perturbation of mitochondrial membrane integrity and a diminution in
      ATP biosynthesis. Furthermore, several proteins were identified that were
      involved in energy and secondary metabolism; the changes in accumulation of these
      proteins were observed with 100 MUM MeJA. In conclusion, our results suggest that
      a switch of the metabolic fate of hairy roots in response to MeJA could cause an
      increase in the accumulation of secondary metabolites. This is likely to have
      important consequences in the production of specific alkaloids important for the
      pharmaceutical industry.

PMID- 21727182
TI  - An essential protective role of IL-10 in the immunological mechanism underlying
      resistance vs. susceptibility to lupus induction by dendritic cells and dying
      cells.
AB  - OBJECTIVE: To define the role of IL-10 in lupus pathogenesis, and to understand
      the immunological mechanisms underlying resistance vs susceptibility to lupus
      disease induction by dendritic cells (DCs) and dying cells. METHODS: Groups of IL
      10-deficient and normal C57BL/6 mice were injected with syngenic DCs that had
      ingested necrotic cells prepared by either freeze-thaw cycle (DC/nec(F/T)) or
      heat shock (DC/nec(H/S)) procedures, or with DC or necrotic cells alone, or with
      PBS only. Disease development, including proteinuria and renal pathological
      changes, was monitored. Levels of autoantibodies against different lupus
      associated nuclear antigens were measured by ELISAs, and IC deposition in the
      kidneys was confirmed by immunostaining. RESULTS: No significant proteinuria was
      detected in the mice. However, striking renal pathological changes typical of IC
      mediated GN were consistently observed in the DC/nec(F/T)-treated IL-10(-/-)
      mice. These included glomerular hypercellularity and macrophage infiltration,
      renal IC deposition, circulating kidney-reactive autoantibodies and the presence
      of immunoglobulin G2 isotype-specific antibody complexes in the diseased kidneys.
      We demonstrated further that host-derived IL-10 was primarily responsible for
      protecting against the induction of pathogenic Th1 type of autoantibody responses
      in the mice. CONCLUSION: IL-10 protects against the induction of lupus-like renal
      end-organ damage by down-regulating pathogenic Th1 responses.

PMID- 21727183
TI  - The use of mathematical models to inform influenza pandemic preparedness and
      response.
AB  - Influenza pandemics have occurred throughout history and were associated with
      substantial excess mortality and morbidity. Mathematical models of infectious
      diseases permit quantitative description of epidemic processes based on the
      underlying biological mechanisms. Mathematical models have been widely used in
      the past decade to aid pandemic planning by allowing detailed predictions of the
      speed of spread of an influenza pandemic and the likely effectiveness of
      alternative control strategies. During the initial waves of the 2009 influenza
      pandemic, mathematical models were used to track the spread of the virus, predict
      the time course of the pandemic and assess the likely impact of large-scale
      vaccination. While mathematical modeling has made substantial contributions to
      influenza pandemic preparedness, its use as a realtime tool for pandemic control
      is currently limited by the lack of essential surveillance information such as
      serological data. Mathematical modeling provided a useful framework for analyzing
      and interpreting surveillance data during the 2009 influenza pandemic, for
      highlighting limitations in existing pandemic surveillance systems, and for
      guiding how these systems should be strengthened in order to cope with future
      epidemics of influenza or other emerging infectious diseases.

PMID- 21727184
TI  - Structural basis and sequence co-evolution analysis of the hemagglutinin protein
      of pandemic influenza A/H1N1 (2009) virus.
AB  - Severe pandemic influenza A H1N1 (2009) infection, especially in the lower
      respiratory tract, is often associated with the virus carrying a D222G
      substitution in the hemagglutinin (HA) protein of the virus. The mechanism for
      this association has not been fully explored. In the in vitro binding assay, it
      was found that clinical isolates carrying D222G substitution exhibit higher
      binding avidity to 2,3-linked sialic acids than the wild-type virus. The receptor
      binding pocket of the pandemic influenza (H1N1) HA was found to be smaller than
      those of other influenza A strains, allowing tighter binding of the virus with
      the receptor, yet also inducing steric stress for the binding. Our homology
      modeling and molecular docking calculations implicated that residue 222 may
      affect the positioning of the conserved Q223 residue, hence modulating
      flexibility of the binding pocket and steric hindrance during receptor binding.
      The molecular property of residue 222 can also directly influence the 'lysine
      fence' via the polarity of the amino acid residue where D222G substitution will
      enhance the electrostatic interactions between the receptor and the protein. The
      potential importance of residue 222 was illustrated by evolutionary analysis,
      which showed that this site is under intense selection pressure during adaptation
      of the virus to human host. Our findings provide a useful reference for follow-up
      studies in monitoring the ongoing evolution of the pandemic influenza A H1N1
      (2009) virus.

PMID- 21727185
TI  - Genome-wide screening using RNA interference to study host factors in viral
      replication and pathogenesis.
AB  - With the recent development of short interfering RNA and short hairpin RNA
      expression libraries, RNA interference (RNAi) technology has been extensively
      employed to identify genes involved in diverse cellular processes, such as signal
      transduction, cell cycle, cancer biology and host-pathogen interactions. In the
      field of viral infection, this approach has already identified hundreds of new
      genes not previously known to be important for various virus lifecycles. In this
      brief review, we focus on recent studies performed using genome-wide RNAi-based
      screens in mammalian cells for the identification of essential host factors for
      viral infection and pathogenesis.

PMID- 21727186
TI  - Oxalate nephropathy in a laboratory colony of common marmoset monkeys (Callithrix
      jacchus) following the ingestion of Eucalyptus viminalis.
AB  - Seven common marmoset monkeys (Callithrix jacchus) from a laboratory colony of 17
      died over a period of eight months. Death of six of these monkeys was attributed
      to kidney failure from an oxalate-induced nephropathy. The epidemiology of this
      outbreak suggested an exogenous source and there was strong evidence that the
      source was bark and leaves from an Eucalyptus viminalis tree. Branches of this
      tree were introduced one month before the first death. The branches were removed
      one month after deaths commenced, but deaths continued for another five months.
      Urinalysis of all surviving marmosets at 80 and 122 days after initial contact
      with the E viminalis branches suggested that these monkeys had renal impairment.
      In the cases described here, the eating behaviour of common marmosets apparently
      exposed the animals to toxic levels of oxalate in the bark and leaves of an E
      viminalis tree.

PMID- 21727187
TI  - Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell
      acute lymphoblastic leukemia.
AB  - The MYC oncogenic transcription factor is overexpressed in most human cases of T
      cell acute lymphoblastic leukemia (T-ALL), often downstream of mutational NOTCH1
      activation. Genetic alterations in the PTEN-PI3K-AKT pathway are also common in T
      ALL. We generated a conditional zebrafish model of T-ALL in which 4
      hydroxytamoxifen (4HT) treatment induces MYC activation and disease, and
      withdrawal of 4HT results in T-ALL apoptosis and tumor regression. However, we
      found that loss-of-function mutations in zebrafish pten genes, or expression of a
      constitutively active Akt2 transgene, rendered tumors independent of the MYC
      oncogene and promoted disease progression after 4HT withdrawal. Moreover, MYC
      suppresses pten mRNA levels, suggesting that Akt pathway activation downstream of
      MYC promotes tumor progression. Our findings indicate that Akt pathway activation
      is sufficient for tumor maintenance in this model, even after loss of survival
      signals driven by the MYC oncogene.

PMID- 21727188
TI  - Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic
      mucocutaneous candidiasis.
AB  - Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal
      dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency.
      Here, using whole-exome sequencing, we identified heterozygous germline mutations
      in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described
      heterozygous STAT1 mutant alleles are loss-of-function and cause AD
      predisposition to mycobacterial disease caused by impaired STAT1-dependent
      cellular responses to IFN-gamma. Other loss-of-function STAT1 alleles cause AR
      predisposition to intracellular bacterial and viral diseases, caused by impaired
      STAT1-dependent responses to IFN-alpha/beta, IFN-gamma, IFN-lambda, and IL-27. In
      contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of
      function and increase STAT1-dependent cellular responses to these cytokines, and
      to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of
      these mutations affect the coiled-coil domain and impair the nuclear
      dephosphorylation of activated STAT1, accounting for their gain-of-function and
      dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors
      IFN-alpha/beta, IFN-gamma, and IL-27, and stronger STAT1 activation in response
      to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T
      cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles
      therefore cause AD CMCD by impairing IL-17 immunity.

PMID- 21727189
TI  - The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive
      immune responses.
AB  - DAP12, an immunoreceptor tyrosine-based activation motif-bearing adapter protein,
      is involved in innate immunity mediated by natural killer cells and myeloid
      cells. We show that DAP12-deficient mouse B cells and B cells from a patient with
      Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12,
      showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid
      associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated
      immune receptor. Like DAP12-deficient B cells, MAIR-II-deficient B cells were
      hyperresponsive. Expression of a chimeric receptor composed of the MAIR-II
      extracellular domain directly coupled to DAP12 into the DAP12-deficient or MAIR
      II-deficient B cells suppressed B cell receptor (BCR)-mediated proliferation. The
      chimeric MAIR-II-DAP12 receptor recruited the SH2 domain-containing protein
      tyrosine phosphatase 1 (SHP-1) after BCR stimulation. DAP12-deficient mice showed
      elevated serum antibodies against self-antigens and enhanced humoral immune
      responses against T cell-dependent and T cell-independent antigens. Thus, DAP12
      coupled MAIR-II negatively regulates B cell-mediated adaptive immune responses.

PMID- 21727190
TI  - Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity.
AB  - B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a
      broad range of nonhematopoietic organs, suggesting a role in maintaining
      peripheral tolerance. As endogenous B7x protein is expressed in pancreatic
      islets, we investigated whether the molecule inhibits diabetogenic responses.
      Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a
      more aggressive form of diabetes than in wild-type animals. This exacerbation of
      disease correlated with higher frequencies of islet-infiltrating Th1 and Th17
      cells. Conversely, local B7x overexpression inhibited the development of
      autoimmunity, as crossing diabetes-susceptible BDC2.5/B6(g7) mice to animals
      overexpressing B7x in pancreatic islets abrogated disease induction. This
      protection was caused by the inhibition of IFN-gamma production by CD4 T cells
      and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive
      function of B7x was also supported by observations from another autoimmune model,
      experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed
      exacerbated disease in comparison with wild-type animals. Analysis of central
      nervous system-infiltrating immune cells revealed that the loss of endogenous B7x
      resulted in expanded Th1 and Th17 responses. Data from these two autoimmune
      models provide evidence that B7x expression in the periphery acts as an immune
      checkpoint to prevent tissue-specific autoimmunity.

PMID- 21727192
TI  - Transient binding of an activator BH3 domain to the Bak BH3-binding groove
      initiates Bak oligomerization.
AB  - The mechanism by which the proapoptotic Bcl-2 family members Bax and Bak release
      cytochrome c from mitochondria is incompletely understood. In this paper, we show
      that activator BH3-only proteins bind tightly but transiently to the Bak
      hydrophobic BH3-binding groove to induce Bak oligomerization, liposome
      permeabilization, mitochondrial cytochrome c release, and cell death. Analysis by
      surface plasmon resonance indicated that the initial binding of BH3-only proteins
      to Bak occurred with similar kinetics with or without detergent or mitochondrial
      lipids, but these reagents increase the strength of the Bak-BH3-only protein
      interaction. Point mutations in Bak and reciprocal mutations in the BH3-only
      proteins not only confirmed the identity of the interacting residues at the Bak
      BH3-only protein interface but also demonstrated specificity of complex formation
      in vitro and in a cellular context. These observations indicate that transient
      protein-protein interactions involving the Bak BH3-binding groove initiate Bak
      oligomerization and activation.

PMID- 21727191
TI  - Integrating mechanisms of pulmonary fibrosis.
AB  - Pulmonary fibrosis is a highly heterogeneous and lethal pathological process with
      limited therapeutic options. Although research on the pathogenesis of pulmonary
      fibrosis has frequently focused on the mechanisms that regulate the
      proliferation, activation, and differentiation of collagen-secreting
      myofibroblasts, recent studies have identified new pathogenic mechanisms that are
      critically involved in the initiation and progression of fibrosis in a variety of
      settings. A more detailed and integrated understanding of the cellular and
      molecular mechanisms of pulmonary fibrosis could help pave the way for effective
      therapeutics for this devastating and complex disease.

PMID- 21727193
TI  - Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC-spindle
      interaction to ensure proper microtubule dynamics.
AB  - Dynamic microtubules facilitate chromosome arrangement before anaphase, whereas
      during anaphase microtubule stability assists chromosome separation. Changes in
      microtubule dynamics at the metaphase-anaphase transition are regulated by Cdk1.
      Cdk1-mediated phosphorylation of Sli15/INCENP promotes preanaphase microtubule
      dynamics by preventing chromosomal passenger complex (CPC; Sli15/INCENP,
      Bir1/Survivin, Nbl1/Borealin, Ipl1/Aurora) association with spindles. However,
      whether Cdk1 has sole control over microtubule dynamics, and how CPC-microtubule
      association influences microtubule behavior, are unclear. Here, we show that
      Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP modulates microtubule
      dynamics by preventing CPC binding to the preanaphase spindle and to the central
      spindle until late anaphase, facilitating spatiotemporal control of microtubule
      dynamics required for proper metaphase centromere positioning and anaphase
      spindle elongation. Decreased Ipl1-dependent Sli15 phosphorylation drives direct
      CPC binding to microtubules, revealing how the CPC influences microtubule
      dynamics. We propose that Cdk1 and Ipl1/Aurora cooperatively modulate microtubule
      dynamics and that Ipl1/Aurora-dependent phosphorylation of Sli15 controls spindle
      function by excluding the CPC from spindle regions engaged in microtubule
      polymerization.

PMID- 21727194
TI  - Sorting of GPI-anchored proteins into ER exit sites by p24 proteins is dependent
      on remodeled GPI.
AB  - Glycosylphosphatidylinositol (GPI) anchoring of proteins is a posttranslational
      modification occurring in the endoplasmic reticulum (ER). After GPI attachment,
      proteins are transported by coat protein complex II (COPII)-coated vesicles from
      the ER. Because GPI-anchored proteins (GPI-APs) are localized in the lumen, they
      cannot interact with cytosolic COPII components directly. Receptors that link GPI
      APs to COPII are thought to be involved in efficient packaging of GPI-APs into
      vesicles; however, mechanisms of GPI-AP sorting are not well understood. Here we
      describe two remodeling reactions for GPI anchors, mediated by PGAP1 and PGAP5,
      which were required for sorting of GPI-APs to ER exit sites. The p24 family of
      proteins recognized the remodeled GPI-APs and sorted them into COPII vesicles.
      Association of p24 proteins with GPI-APs was pH dependent, which suggests that
      they bind in the ER and dissociate in post-ER acidic compartments. Our results
      indicate that p24 complexes act as cargo receptors for correctly remodeled GPI
      APs to be sorted into COPII vesicles.

PMID- 21727195
TI  - Cytoplasmic gamma-actin and tropomodulin isoforms link to the sarcoplasmic
      reticulum in skeletal muscle fibers.
AB  - The sarcoplasmic reticulum (SR) serves as the Ca(2+) reservoir for muscle
      contraction. Tropomodulins (Tmods) cap filamentous actin (F-actin) pointed ends,
      bind tropomyosins (Tms), and regulate F-actin organization. In this paper, we use
      a genetic targeting approach to examine the effect of Tmod1 deletion on the
      organization of cytoplasmic gamma-actin (gamma(cyto)-actin) in the SR of skeletal
      muscle. In wild-type muscle fibers, gamma(cyto)-actin and Tmod3 defined an SR
      microdomain that was distinct from another Z line-flanking SR microdomain
      containing Tmod1 and Tmod4. The gamma(cyto)-actin/Tmod3 microdomain contained an
      M line complex composed of small ankyrin 1.5 (sAnk1.5), gamma(cyto)-actin, Tmod3,
      Tm4, and Tm5NM1. Tmod1 deletion caused Tmod3 to leave its SR compartment, leading
      to mislocalization and destabilization of the Tmod3-gamma(cyto)-actin-sAnk1.5
      complex. This was accompanied by SR morphological defects, impaired Ca(2+)
      release, and an age-dependent increase in sarcomere misalignment. Thus, Tmod3
      regulates SR-associated gamma(cyto)-actin architecture, mechanically stabilizes
      the SR via a novel cytoskeletal linkage to sAnk1.5, and maintains the alignment
      of adjacent myofibrils.

PMID- 21727196
TI  - The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail,
      Slug, and Sip1.
AB  - A small group of core transcription factors, including Twist, Snail, Slug, and
      Sip1, control epithelial-mesenchymal transitions (EMTs) during both embryonic
      development and tumor metastasis. However, little is known about how these
      factors are coordinately regulated to mediate the requisite behavioral and fate
      changes. It was recently shown that a key mechanism for regulating Snail proteins
      is by modulating their stability. In this paper, we report that the stability of
      Twist is also regulated by the ubiquitin-proteasome system. We found that the
      same E3 ubiquitin ligase known to regulate Snail family proteins, Partner of
      paired (Ppa), also controlled Twist stability and did so in a manner dependent on
      the Twist WR-rich domain. Surprisingly, Ppa could also target the third core EMT
      regulatory factor Sip1 for proteasomal degradation. Together, these results
      indicate that despite the structural diversity of the core transcriptional
      regulatory factors implicated in EMT, a common mechanism has evolved for
      controlling their stability and therefore their function.

PMID- 21727197
TI  - POM121 and Sun1 play a role in early steps of interphase NPC assembly.
AB  - Nuclear pore complexes (NPCs) assemble at the end of mitosis during nuclear
      envelope (NE) reformation and into an intact NE as cells progress through
      interphase. Although recent studies have shown that NPC formation occurs by two
      different molecular mechanisms at two distinct cell cycle stages, little is known
      about the molecular players that mediate the fusion of the outer and inner
      nuclear membranes to form pores. In this paper, we provide evidence that the
      transmembrane nucleoporin (Nup), POM121, but not the Nup107-160 complex, is
      present at new pore assembly sites at a time that coincides with inner nuclear
      membrane (INM) and outer nuclear membrane (ONM) fusion. Overexpression of POM121
      resulted in juxtaposition of the INM and ONM. Additionally, Sun1, an INM protein
      that is known to interact with the cytoskeleton, was specifically required for
      interphase assembly and localized with POM121 at forming pores. We propose a
      model in which POM121 and Sun1 interact transiently to promote early steps of
      interphase NPC assembly.

PMID- 21727198
TI  - 1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung
      cancer.
AB  - The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland
      on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of
      leading professionals in pathology and molecular diagnostics and medical,
      surgical and radiation oncology. Before the conference, the expert panel prepared
      clinically relevant questions concerning five areas as follows: early and locally
      advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second
      /third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung
      cancer (SCLC) to be addressed through discussion at the Consensus Conference. All
      relevant scientific literature for each question was reviewed in advance. During
      the Consensus Conference, the panel developed recommendations for each specific
      question. The consensus agreement in SCLC is reported in this article. The
      recommendations detailed here are based on an expert consensus after careful
      review of published data. All participants have approved this final update.

PMID- 21727199
TI  - Identifying continuous quality improvement publications: what makes an
      improvement intervention 'CQI'?
AB  - BACKGROUND: The term continuous quality improvement (CQI) is often used to refer
      to a method for improving care, but no consensus statement exists on the
      definition of CQI. Evidence reviews are critical for advancing science, and
      depend on reliable definitions for article selection. METHODS: As a preliminary
      step towards improving CQI evidence reviews, this study aimed to use expert panel
      methods to identify key CQI definitional features and develop and test a
      screening instrument for reliably identifying articles with the key features. We
      used a previously published method to identify 106 articles meeting the general
      definition of a quality improvement intervention (QII) from 9427 electronically
      identified articles from PubMed. Two raters then applied a six-item CQI screen to
      the 106 articles. RESULTS: Per cent agreement ranged from 55.7% to 75.5% for the
      six items, and reviewer-adjusted intra-class correlation ranged from 0.43 to
      0.62. 'Feedback of systematically collected data' was the most common feature
      (64%), followed by being at least 'somewhat' adapted to local conditions (61%),
      feedback at meetings involving participant leaders (46%), using an iterative
      development process (40%), being at least 'somewhat' data driven (34%), and using
      a recognised change method (28%). All six features were present in 14.2% of QII
      articles. CONCLUSIONS: We conclude that CQI features can be extracted from QII
      articles with reasonable reliability, but only a small proportion of QII articles
      include all features. Further consensus development is needed to support
      meaningful use of the term CQI for scientific communication.

PMID- 21727200
TI  - Comparison of the characteristics of fire and non-fire households in the 2004
      2005 survey of fire department-attended and unattended fires.
AB  - OBJECTIVE: Comparison of characteristics of fire with non-fire households to
      determine factors differentially associated with fire households (fire risk
      factors). DESIGN, SETTING AND SUBJECTS: National household telephone survey in
      2004-2005 by the US Consumer Product Safety Commission with 916 fire households
      and a comparison sample of 2161 non-fire households. There were an estimated 7.4
      million fires (96.6% not reported to fire departments) with 130,000 injuries.
      MAIN OUTCOME MEASURE: Bivariate analysis and multivariate logistic regression
      analyses to assess differences in household characteristics. RESULTS: Significant
      factors associated with fire households were renting vs. owning (OR 1.988
      p<0.0001); household members under 18 year of age (OR 1.277 p<0.0001); lack of
      residents over 64 years old (OR 0.552 p=0.0007); and college or higher education
      (some college OR 1.444 p=0.0360, college graduate OR 1.873, p<0.0001,
      postgraduate OR 2.156 p<0.0001). Not significant were age of house; race;
      ethnicity; and income. Number of smokers was borderline significant (OR 1.132
      p=0.1019) but was significant in the subset of fire households with non-cooking
      fires (OR 1.383 p=0.0011). Single family houses were associated with non-fire
      households in the bivariate analysis but not in the multivariate analyses.
      CONCLUSION: Renting, household members under 18 years old and smokers are risk
      factors for unattended fires, similar to the literature for fatal and injury
      fires. Differences included household members over 65 years old (associated with
      non-fire households), college/postgraduate education (associated with fire
      households) and lack of significance of income. Preventing cooking fires (64% of
      survey incidents), smoking prevention efforts and fire prevention education for
      families with young children have the potential for reducing unattended fires and
      injuries.

PMID- 21727201
TI  - Early measurements of plasma matrix metalloproteinase-2 predict infarct size and
      ventricular dysfunction in ST-elevation myocardial infarction.
AB  - BACKGROUND: Immediate reopening of the acutely occluded infarct-related artery
      via primary PCI is the preferred treatment in ST-elevation myocardial infarction
      (STEMI). However, the sudden reinitiation of blood flow can lead to a local acute
      inflammatory response with further endothelial and myocardial damage, so-called
      reperfusion injury. The activation of matrix metalloproteinases (MMPs) is
      suggested to be a key event in this process. OBJECTIVES: To investigate
      circulating MMPs, tissue inhibitors of metalloproteinases (TIMPs) and
      myeloperoxidase (MPO) in relation to infarct size, left ventricular dysfunction
      and remodelling in a STEMI population undergoing PCI. METHODS: 58 Patients with
      STEMI undergoing primary PCI were included. Blood samples were collected at
      baseline before PCI and at 12, 24 and 48 h for later analysis of MMPs, TIMPs and
      MPO by ELISA. Infarct size, left ventricular (LV) dysfunction and remodelling
      were assessed by cardiac MRI at 5 days and 4 month after STEMI. RESULTS: Plasma
      MMP-2 at 0 and 12 h showed a consistent and significant correlation with infarct
      size and LV dysfunction measured both at 5 days and at 4 months and correlated
      well with troponin I measurements. For TIMP-1 and TIMP-2 some support was found
      for associations with infarct size and LV dysfunction, but these were not as
      consistent as for MMP-2. MMP-8, MMP-9 and MPO did not overall correlate with
      measures of infarct size, LV dysfunction or remodelling. CONCLUSIONS: In patients
      with STEMI, circulating levels of MMP-2, measured early and even before
      reperfusion therapy, are strongly associated with infarct size and LV
      dysfunction. This provides further evidence for the role of MMP-2 in ischaemia
      reperfusion injury.

PMID- 21727202
TI  - Pathophysiological changes after cardiac transplantation: the role of chronic
      inflammation and rejection.

PMID- 21727203
TI  - Population-based proband-oriented pedigree information system: application to
      hypertension with population-based screening data (KCIS No. 25).
AB  - OBJECTIVE: To develop a population-based proband-oriented pedigree information
      system that can be easily applied to various diseases in genetic epidemiological
      studies, making allowance for the capture of theoretical family relationships.
      DESIGNS AND MEASUREMENTS: A population-based proband-oriented pedigree
      information system with ties of consanguinity based on both population-based
      household registry data and Keelung Community Integrated Screening data was
      proposed to build a comprehensive extended family pedigree structure to
      accommodate a series of genetic studies on different diseases. We also developed
      an algorithm to efficiently assess how well theoretical family relationships
      affecting the occurrence of diseases across three generations with respect to the
      relative relationship score, a quantitative indicator of genetic influence, were
      captured. RESULTS: We applied this population-based proband-oriented pedigree
      information system to estimate the rate of hypertension with various relative
      relationships given the selection of probands. The degree of capturing complete
      familial relationships was assessed for three generations. The risk for early
      onset of hypertension was proportional to the proband-oriented relative
      relationship score with 2% increased risk and 1% correction for incomplete
      capture. CONCLUSIONS: The population-based proband-oriented pedigree information
      system is powerful and can support various genetic descriptive and analytic
      epidemiological studies.

PMID- 21727204
TI  - Reconciliation of the cloud computing model with US federal electronic health
      record regulations.
AB  - Cloud computing refers to subscription-based, fee-for-service utilization of
      computer hardware and software over the Internet. The model is gaining acceptance
      for business information technology (IT) applications because it allows capacity
      and functionality to increase on the fly without major investment in
      infrastructure, personnel or licensing fees. Large IT investments can be
      converted to a series of smaller operating expenses. Cloud architectures could
      potentially be superior to traditional electronic health record (EHR) designs in
      terms of economy, efficiency and utility. A central issue for EHR developers in
      the US is that these systems are constrained by federal regulatory legislation
      and oversight. These laws focus on security and privacy, which are well
      recognized challenges for cloud computing systems in general. EHRs built with the
      cloud computing model can achieve acceptable privacy and security through
      business associate contracts with cloud providers that specify compliance
      requirements, performance metrics and liability sharing.

PMID- 21727205
TI  - There is no neutral position on fraud!
AB  - In 2005, Dr David Brailer, our first National Coordinator for Health Information
      Technology, had a vision of widespread adoption of electronic health records
      connected through networks run by regional health-information organizations. An
      advisory panel recommended at that time that proactive fraud management functions
      be embedded in this emerging information infrastructure. This has not occurred.
      Currently, the agencies responsible for fraud need the assistance of the Office
      of the National Coordinator for Health Information Technology in order to most
      effectively manage the growing problem of fraud related to the adoption of
      electronic health records and health-information exchanges.

PMID- 21727206
TI  - Commercial off-the-shelf consumer health informatics interventions:
      recommendations for their design, evaluation and redesign.
AB  - OBJECTIVE: The goal of this paper is to describe the successful application of a
      use case-based evaluation approach to guide the effective design, evaluation and
      redesign of inexpensive, commercial, off-the-shelf consumer health informatics
      (CHI) interventions. DESIGN: Researchers developed four CHI intervention use
      cases representing two distinct patient populations (patients with diabetes with
      high blood pressure, post-bariatric surgery patients), two commercial off-the
      shelf CHI applications (Microsoft HealthVault, Google Health), and related
      devices (blood pressure monitor, pedometer, weight scale). Three patient proxies
      tested each intervention for 10 days. MEASUREMENTS: The patient proxies recorded
      their challenges while completing use case tasks, rating the severity of each
      challenge based on how much it hindered their use of the intervention. Two
      independent evaluators categorized the challenges by human factors domain
      (physical, cognitive, macroergonomic). RESULTS: The use case-based approach
      resulted in the identification of 122 challenges, with 12% physical, 50%
      cognitive and 38% macroergonomic. Thirty-nine challenges (32%) were at least
      moderately severe. Nine of 22 use case tasks (41%) accounted for 72% of the
      challenges. LIMITATIONS: The study used two patient proxies and addressed two
      specific patient populations and low-cost, off-the-shelf CHI interventions, which
      may not perfectly generalize to a larger number of proxies, actual patient
      populations, or other CHI interventions. CONCLUSION: CHI designers can employ the
      use case-based evaluation approach to assess the fit of a CHI intervention with
      patients' health work, in the context of their daily activities and environment,
      which would be difficult or impossible to evaluate by laboratory-based studies.

PMID- 21727207
TI  - Evolution of mouse models for studying CNS cancer: a decade of progress.

PMID- 21727208
TI  - Report from the fifth National Cancer Institute Mouse Models of Human Cancers
      Consortium Nervous System Tumors Workshop.
AB  - Cancers of the nervous system are clinically challenging tumors that present with
      varied histopathologies and genetic etiologies. While the prognosis for the most
      malignant of these tumors is essentially unchanged despite decades of basic and
      translational science research, the past few years have witnessed the
      identification of numerous targetable molecular alterations in these cancers.
      With the advent of advanced genomic sequencing methodologies and the development
      of accurate small-animal models of these nervous system cancers, we are now
      ideally positioned to develop personalized therapies that target the unique
      cellular and molecular changes that define their formation and drive their
      continued growth. Recently, the National Cancer Institute convened a workshop to
      advance our understanding of nervous system cancer mouse models and to inform
      clinical trials by reconsidering these neoplasms as complex biological systems
      characterized by heterogeneity at all levels.

PMID- 21727209
TI  - Local delivery of rapamycin: a toxicity and efficacy study in an experimental
      malignant glioma model in rats.
AB  - Rapamycin, an anti-proliferative agent, is effective in the treatment of renal
      cell carcinoma and recurrent breast cancers. We proposed that this potent
      mammalian target of rapamycin inhibitor may be useful for the treatment of
      gliomas as well. We examined the cytotoxicity of rapamycin against a rodent
      glioma cell line, determined the toxicity of rapamycin when delivered
      intracranially, and investigated the efficacy of local delivery of rapamycin for
      the treatment of experimental malignant glioma in vivo. We also examined the dose
      dependent efficacy of rapamycin and the effect when locally delivered rapamycin
      was combined with radiation therapy. Rapamycin was cytotoxic to 9L cells, causing
      34% growth inhibition at a concentration of 0.01 ug/mL. No in vivo toxicity was
      observed when rapamycin was incorporated into biodegradable caprolactone
      glycolide (35:65) polymer beads at 0.3%, 3%, and 30% loading doses and implanted
      intracranially. Three separate efficacy studies were performed to test the
      reproducibility of the effect of the rapamycin beads as well as the validity of
      this treatment approach. Animals treated with the highest dose of rapamycin beads
      tested (30%) consistently demonstrated significantly longer survival durations
      than the control and placebo groups. All dose-escalating rapamycin bead treatment
      groups (0.3%, 3% and 30%), treated both concurrently with tumor and in a delayed
      manner after tumor placement, experienced a significant increase in survival,
      compared with controls. Radiation therapy in addition to the simultaneous
      treatment with 30% rapamycin beads led to significantly longer survival duration
      than either therapy alone. These results suggest that the local delivery of
      rapamycin for the treatment of gliomas should be further investigated.

PMID- 21727210
TI  - Protein kinase D2 is a novel regulator of glioblastoma growth and tumor
      formation.
AB  - Glioblastoma multiforme, a highly aggressive tumor of the central nervous system,
      has a dismal prognosis that is due in part to its resistance to radio- and
      chemotherapy. The protein kinase C (PKC) family of serine threonine kinases has
      been implicated in the formation and proliferation of glioblastoma multiforme.
      Members of the protein kinase D (PKD) family, which consists of PKD1, -2 and, -3,
      are prominent downstream targets of PKCs and could play a major role in
      glioblastoma growth. PKD2 was highly expressed in both low-grade and high-grade
      human gliomas. The number of PKD2-positive tumor cells increased with glioma
      grading (P < .001). PKD2 was also expressed in CD133-positive glioblastoma stem
      cells and various glioblastoma cell lines in which the kinase was found to be
      constitutively active. Inhibition of PKDs by pharmacological inhibitors resulted
      in substantial inhibition of glioblastoma proliferation. Furthermore, specific
      depletion of PKD2 by siRNA resulted in a marked inhibition of anchorage-dependent
      and -independent proliferation and an accumulation of glioblastoma cells in
      G0/G1, accompanied by a down-regulation of cyclin D1 expression. In addition,
      PKD2-depleted glioblastoma cells exhibited substantially reduced tumor formation
      in vivo on chicken chorioallantoic membranes. These findings identify PKD2 as a
      novel mediator of glioblastoma cell growth in vitro and in vivo and thereby as a
      potential therapeutic target for this devastating disease.

PMID- 21727211
TI  - Is there a common upstream link for autophagic and apoptotic cell death in human
      high-grade gliomas?
AB  - The prognosis of patients with human high-grade gliomas (HGGs) remains dismal
      despite major advances in their management, due mainly to the high resistance of
      these infiltrative tumor cells to programmed cell death (PCD). Most therapeutic
      strategies for HGGs are aimed to maximize PCD type I, apoptosis or type II,
      autophagy. These are predominantly distinctive processes, but many studies
      suggest a cross-talk between the two. A better understanding of the link between
      PCD types I and II might allow development of more effective therapies for HGGs.
      In this study, we examined whether there is a common upstream signaling event
      responsible for both apoptotic and autophagic PCD using 3 chemotherapeutic agents
      in human HGG cells. Our study shows that each agent caused a significant decrease
      in cell viability in each of the HGG cell lines tested. The increase rate of
      apoptosis and autophagy varied among cell lines and chemotherapeutic agents used.
      Increased expression of cytidine-cytidine-adenosine-adenosine-thymidine
      (C)/enhancer binding protein (EBP) homologous transcription factor C/EBP
      homologous protein (CHOP)/growth arrest and DNA damage-inducible gene 153
      (GADD153) was documented after use of either pro-autophagic or pro-apoptotic
      agents. The involvement of CHOP/GADD153 in both type I and type II PCD was
      confirmed by overexpression and gene-silencing studies. Gene silencing by small
      interfering RNA-mediated CHOP/GADD153 resulted in increased cell viability,
      decreased upregulation of microtubule-associated protein light-chain 3' type II
      (LC3II) and cleaved caspase-3, and inhibition of apoptosis and autophagy.
      Exogenous expression of CHOP/GADD153 triggered apoptosis and autophagy in the
      absence of other stimuli. The clinical significance of these findings was
      supported by the evidence that celecoxib, a nonsteroidal anti-inflammatory drug
      known to induce GADD153-mediated apoptosis, strongly increases both type I and
      type II PCD in HGG cells when combined with another inducer of GADD153. These
      data suggest that CHOP/GADD153 should be investigated as a novel targetable
      signaling step to improve therapies for HGGs.

PMID- 21727212
TI  - Nilotinib alone or in combination with selumetinib is a drug candidate for
      neurofibromatosis type 2.
AB  - Loss of the tumor suppressor merlin is a cause of frequent tumors of the nervous
      system, such as schwannomas, meningiomas, and ependymomas, which occur
      spontaneously or as part of neurofibromatosis type 2 (NF2). Because there is
      medical need for drug therapies for these tumors, our aim is to find therapeutic
      targets. We have studied the pathobiology of schwannomas, because they are the
      most common merlin-deficient tumors and are a model for all merlin-deficient
      tumors. With use of a human schwannoma in vitro model, we previously described
      strong overexpression/activation of platelet-derived growth factor receptor-beta
      (PDGFR-beta) leading to strong, long-lasting activation of extracellular-signal
      regulated kinase (ERK1/2) and AKT and increased schwannoma growth, which we
      successfully inhibited using the PDGFR/Raf inhibitor sorafenib. However, the
      benign character of schwannomas may require long-term treatment; thus, drug
      tolerability is an issue. With the use of Western blotting, proliferation assays,
      viability assays, and a primary human schwannoma cell in vitro model, we tested
      the PDGFR/c-KIT inhibitors imatinib (Glivec(;) Novartis) and nilotinib
      (Tasigna(;) Novartis). Imatinib and nilotinib inhibited PDGF-DD-mediated ERK1/2
      activation, basal and PDGF-DD-mediated activation of PDGFR-beta and AKT, and
      schwannoma proliferation. Nilotinib is more potent than imatinib, exerting its
      maximal inhibitory effect at concentrations lower than steady-state trough plasma
      levels. In addition, nilotinib combined with the MEK1/2 inhibitor selumetinib
      (AZD6244) at low concentrations displayed stronger efficiency toward tumor growth
      inhibition, compared with nilotinib alone. We suggest that therapy with nilotinib
      or combinational therapy that  simultaneously inhibits PDGFR and the downstream
      Raf/MEK1/2/ERK1/2 pathway could represent an effective treatment for schwannomas
      and other merlin-deficient tumors.

PMID- 21727213
TI  - Peri-ictal pseudoprogression in patients with brain tumor.
AB  - Recent advances in the treatment of malignant gliomas have highlighted the fact
      that the appearance of new contrast-enhancing lesions on magnetic resonance
      imaging (MRI) is not always indicative of tumor recurrence. It has been suggested
      that transient seizure-related MRI changes could mimic disease progression (peri
      ictal pseudoprogression [PIPG]). However, the clinical and MRI features
      associated with this situation have not been well described. Here, we consulted
      the databases of 6 institutions to identify patients with brain tumor who
      presented during the follow-up period transient MRI lesions wrongly suggesting
      tumor progression in a context of epileptic seizures. Ten patients were
      identified. All patients but 1 were long-term survivors who had initially been
      treated with radiotherapy. The PIPG episode occurred after a median interval of
      11 years after radiotherapy. MRI features were highly similar across patients and
      consisted of transient focal cortical and/or leptomeningeal enhancing lesions
      that erroneously suggested tumor progression. All patients improved after
      adjustment of their antiepileptic drugs and transient oral corticosteroids, and
      MRI findings were normalized 3 months after the PIPG episode. Two patients
      demonstrated several seizure relapses with the same clinicoradiological pattern.
      After a median follow-up period of 3.5 years after the initial PIPG episode, only
      1 patient presented with a tumor recurrence. In conclusion, in patients with
      brain tumor, especially in long-term survivors of radiotherapy, the appearance of
      new cortical and/or leptomeningeal contrast-enhancing lesions in a context of
      frequent seizures should raise the suspicion of PIPG. This phenomenon is
      important to recognize in order to avoid futile therapeutic escalation.

PMID- 21727214
TI  - A multicenter study of primary brain tumor incidence in Australia (2000-2008).
AB  - There are conflicting reports from Europe and North America regarding trends in
      the incidence of primary brain tumor, whereas the incidence of primary brain
      tumors in Australia is currently unknown. We aimed to determine the incidence in
      Australia with age-, sex-, and benign-versus-malignant histology-specific
      analyses. A multicenter study was performed in the state of New South Wales (NSW)
      and the Australian Capital Territory (ACT), which has a combined population of >7
      million with >97% rate of population retention for medical care. We
      retrospectively mined pathology databases servicing neurosurgical centers in NSW
      and ACT for histologically confirmed primary brain tumors diagnosed from January
      2000 through December 2008. Data were weighted for patient outflow and data
      completeness. Incidence rates were age standardized and trends analyzed using
      joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed.
      The overall US-standardized incidence of primary brain tumors was 11.3 cases 100
      000 person-years (+/-0.13; 95% confidence interval, 9.8-12.3) during the study
      period with no significant linear increase. A significant increase in primary
      malignant brain tumors from 2000 to 2008 was observed; this appears to be largely
      due to an increase in malignant tumor incidence in the >=65-year age group. This
      collection represents the most contemporary data on primary brain tumor incidence
      in Australia. Whether the observed increase in malignant primary brain tumors,
      particularly in persons aged >=65 years, is due to improved detection, diagnosis,
      and care delivery or a true change in incidence remains undetermined. We
      recommend a direct, uniform, and centralized approach to monitoring primary brain
      tumor incidence that can be independent of multiple interstate cancer registries.

PMID- 21727215
TI  - Pitx2 regulates myosin heavy chain isoform expression and multi-innervation in
      extraocular muscle.
AB  - Extraocular muscle is fundamentally distinct from other skeletal muscle and
      demonstrates specific anatomical divisions, unique innervation, diverse myosin
      isoform expression patterns, a distinct genomic profile and differential
      involvement in neuromuscular disorders. The paired-like homeodomain transcription
      factor 2 (Pitx2) is known to regulate the formation of extraocular muscle
      development and in this report we show that its expression in adulthood also
      defines certain extraocular muscle traits. We found that expression of slow-MyHC
      and slow-tonic MyHC, along with contractile regulatory proteins troponin I and
      troponin T, is reduced during the first 3 weeks after birth in mice with
      conditional knockout of Pitx2, designated Pitx2(Deltaflox/Deltaflox). En grappe
      endplates, which are normally only found on slow-MyHC expressing fibres, were not
      identified in the Pitx2(Deltaflox/Deltaflox) extraocular muscle, suggesting that
      altered innervation was responsible for the loss in slow-MyHC expression.
      Extraocular muscle (EOM)-specific MyHC expressing fibres were dramatically
      reduced at P14 and rarely detected at 3 months in the Pitx2(Deltaflox/Deltaflox)
      mice. 2A-MyHC fibres, which are excluded from mid-belly region in wild-type mice,
      dominated the orbital layer with no apparent longitudinal variation in the
      Pitx2(Deltaflox/Deltaflox) mice. Pure 2X-MyHC fibres, only present at distal ends
      in the wild-type mice, populated the outer global layer in the mid-belly region
      of the Pitx2(Deltaflox/Deltaflox) mice. Pitx2 influences slow-MyHC, slow-tonic
      MyHC and EOM-MyHC expression in extraocular muscle and its absence leads to
      increased expression of 2X-MyHC and 2A-MyHC. Precise definition of the regulation
      of MyHC isoforms in extraocular muscle may allow their rational manipulation, in
      order to alter muscle contractility for therapeutic purposes.

PMID- 21727218
TI  - Intracellular energy status regulates activity in hypocretin/orexin neurones: a
      link between energy and behavioural states.
AB  - The hypocretin/orexin (Hcrt)-containing neurones within the lateral hypothalamus
      integrate nutritional, energetic and behavioural cues to generate the final
      output in order to exert their functions. It is still not clear how Hcrt neurones
      monitor changes in energy status in animals. In brain slices from transgenic mice
      expressing green fluorescent protein (GFP) exclusively in Hcrt neurones, we
      examined the roles of intracellular levels of ATP ([ATP](i)) in regulating
      activities in these cells with conventional and perforated whole-cell recording.
      By using 'ATP clamp' we demonstrated that membrane potential (V(m)) correlated
      with the [ATP](i) in Hcrt neurones. Perforated recording revealed a V(m) of -46.1
      +/- 1.6 mV (n = 18), close to the level measured with an [ATP](i) equal to 5-6 mm
      (-48.7 +/- 1.4 mV, n = 16, 5 mm ATP), suggesting that a unique demand for energy
      is required to maintain normal functionality in Hcrt cells. A direct disruption
      of ATP production or reduction in ambient glucose levels resulted in an
      inhibition of activity in Hcrt neurones. The V(m) was significantly depolarized
      in Hcrt neurones in sleep-deprived mice as compared with controls (P < 0.01, t
      test), which was eliminated by experimental manipulations causing the same level
      of [ATP](i) and K(ATP) channel opening in both groups, suggesting a decrease
      during sleep and an increase during sustained wakefulness in [ATP](i) in Hcrt
      cells. In summary, these data demonstrate that a delicate control of activity by
      monitoring the availability of intracellular energy stores in Hcrt cells may
      serve as a novel mechanism regulating energy expenditure and behavioural state
      dependent upon the energy state in animals.

PMID- 21727219
TI  - Allodynia mediated by C-tactile afferents in human hairy skin.
AB  - We recently showed a contribution of low-threshold cutaneous mechanoreceptors to
      vibration-evoked changes in the perception of muscle pain. Neutral-touch
      stimulation (vibration) of the hairy skin during underlying muscle pain evoked an
      overall increase in pain intensity, i.e. allodynia. This effect appeared to be
      dependent upon cutaneous afferents, as allodynia was abolished by intradermal
      anaesthesia. However, it remains unclear whether allodynia results from
      activation of a single class of cutaneous afferents or the convergence of inputs
      from multiple classes. Intriguingly, no existing human study has examined the
      contribution of C-tactile (CT) afferents to allodynia. Detailed psychophysical
      observations were made in 29 healthy subjects (18 males and 11 females).
      Sustained muscle pain was induced by infusing hypertonic saline (HS: 5%) into
      tibialis anterior muscle (TA). Sinusoidal vibration (200 Hz-200 MUm) was applied
      to the hairy skin overlying TA. Pain ratings were recorded using a visual
      analogue scale (VAS). In order to evaluate the role of myelinated and
      unmyelinated cutaneous afferents in the expression of vibration-evoked allodynia,
      compression block of the sciatic nerve, and low-dose intradermal anaesthesia
      (Xylocaine 0.25%) were used, respectively. In addition, the modulation of muscle
      pain by gentle brushing (1.0 and 3.0 cm s(-1))--known to excite CT fibres--was
      examined. Brushing stimuli were applied to the hairy skin with all fibres intact
      and following the blockade of myelinated afferents. During tonic muscle pain (VAS
      4-6), vibration evoked a significant and reproducible increase in muscle pain
      (allodynia) that persisted following compression of myelinated afferents. During
      compression block, the sense of vibration was abolished, but the vibration-evoked
      allodynia persisted. In contrast, selective anaesthesia of unmyelinated cutaneous
      afferents abolished the allodynia, whereas the percept of vibration remained
      unaffected. Furthermore, allodynia was preserved in the adjacent non
      anaesthetized skin. Conformingly, gentle brushing produced allodynia (at both
      brushing speeds) that persisted during the blockade of myelinated afferents.
      Prior to the induction and following cessation of muscle pain, all subjects
      reported vibration and brushing as non-painful (VAS = 0). These results
      demonstrate that CT fibres in hairy skin mediate allodynia, and that CT-mediated
      inputs have a pluripotent central effect.

PMID- 21727220
TI  - Frontal cerebral cortex blood flow, oxygen delivery and oxygenation during
      normoxic and hypoxic exercise in athletes.
AB  - During maximal hypoxic exercise, a reduction in cerebral oxygen delivery may
      constitute a signal to the central nervous system to terminate exercise. We
      investigated whether the rate of increase in frontal cerebral cortex oxygen
      delivery is limited in hypoxic compared to normoxic exercise. We assessed frontal
      cerebral cortex blood flow using near-infrared spectroscopy and the light
      absorbing tracer indocyanine green dye, as well as frontal cortex oxygen
      saturation (S(tO2)%) in 11 trained cyclists during graded incremental exercise to
      the limit of tolerance (maximal work rate, WRmax) in normoxia and acute hypoxia
      (inspired O2 fraction (F(IO2)), 0.12). In normoxia, frontal cortex blood flow and
      oxygen delivery increased (P < 0.05) from baseline to sub-maximal exercise,
      reaching peak values at near-maximal exercise (80% WRmax: 287 +/- 9 W; 81 +/- 23%
      and 75 +/- 22% increase relative to baseline, respectively), both leveling off
      thereafter up to WRmax (382 +/- 10 W). Frontal cortex S(tO2)% did not change from
      baseline (66 +/- 3%) throughout graded exercise. During hypoxic exercise, frontal
      cortex blood flow increased (P = 0.016) from baseline to sub-maximal exercise,
      peaking at 80% WRmax (213 +/- 6 W; 60 +/- 15% relative increase) before declining
      towards baseline at WRmax (289 +/- 5 W). Despite this, frontal cortex oxygen
      delivery remained unchanged from baseline throughout graded exercise, being at
      WRmax lower than at comparable loads (287 +/- 9 W) in normoxia (by 58 +/- 12%; P
      = 0.01). Frontal cortex S(tO2)% fell from baseline (58 +/- 2%) on light and
      moderate exercise in parallel with arterial oxygen saturation, but then remained
      unchanged to exhaustion (47 +/- 1%). Thus, during maximal, but not light to
      moderate, exercise frontal cortex oxygen delivery is limited in hypoxia compared
      to normoxia. This limitation could potentially constitute the signal to limit
      maximal exercise capacity in hypoxia.

PMID- 21727221
TI  - Short-term plasticity impacts information transfer at glutamate synapses onto
      parvocellular neuroendocrine cells in the paraventricular nucleus of the
      hypothalamus.
AB  - Glutamatergic synaptic inputs onto parvocellular neurosecretory cells (PNCs) in
      the paraventricular nucleus of the hypothalamus (PVN) regulate the hypothalamic
      pituitary-adrenal (HPA) axis responses to stress and undergo stress-dependent
      changes in their capacity to transmit information. In spite of their pivotal role
      in regulating PNCs, relatively little is known about the fundamental rules that
      govern transmission at these synapses. Furthermore, since salient information in
      the nervous system is often transmitted in bursts, it is also important to
      understand the short-term dynamics of glutamate transmission under basal
      conditions. To characterize these properties, we obtained whole-cell patch clamp
      recordings from PNCs in brain slices from postnatal day 21-35 male Sprague-Dawley
      rats and examined EPSCs. EPSCs were elicited by electrically stimulating
      glutamatergic afferents along the periventricular aspect. In response to a paired
      pulse stimulation protocol, EPSCs generally displayed a robust short-term
      depression that recovered within 5 s. Similarly, trains of synaptic stimuli (5-50
      Hz) resulted in a frequency-dependent depression until a near steady state was
      achieved. Application of inhibitors of AMPA receptor (AMPAR) desensitization or
      the low-affinity, competitive AMPAR antagonist failed to affect the depression
      due to paired-pulse and trains of synaptic stimulation indicating that this use
      dependent short-term synaptic depression has a presynaptic locus of expression.
      We used cumulative amplitude profiles during trains of stimulation and variance
      mean analysis to estimate synaptic parameters. Finally, we report that these
      properties contribute to hamper the efficiency with which high frequency synaptic
      inputs generate spikes in PNCs, indicating that these synapses operate as
      effective low-pass filters in basal conditions.

PMID- 21727222
TI  - Subcortical input heterogeneity in the mouse inferior colliculus.
AB  - Simultaneous intracellular recordings of nearby neocortical neurons have
      demonstrated that their membrane potentials are highly correlated. The
      correlation between the spiking activity of nearby neocortical neurons may be
      much smaller, suggesting that inputs are more similar than outputs. Much less is
      known about the similarity of inputs in subcortical sensory areas. Here we
      investigate this question by making simultaneous whole-cell recordings from
      neighbouring neurons in the dorsal cortex of the mouse inferior colliculus. No
      evidence for monosynaptic connections between neighbouring cells was observed,
      suggesting that integration of afferent signals plays a more important role than
      local processing. The correlation between frequency response areas of
      neighbouring cells varied but, surprisingly, neighbouring cells were on average
      not more similar in their responses to tones than non-neighbouring neurons. This
      large micro-heterogeneity suggests a sparse representation of acoustic features
      within the dorsal cortex.

PMID- 21727223
TI  - Delayed-onset rhabdomyolysis after intense exercise.

PMID- 21727224
TI  - Polypharmacy, multiple natural health products and hepatotoxicity.

PMID- 21727228
TI  - Reprocessing single-use devices: an international perspective.

PMID- 21727225
TI  - Risk of serious adverse cardiovascular events associated with varenicline: a
      systematic review and meta-analysis.
AB  - BACKGROUND: There have been postmarketing reports of adverse cardiovascular
      events associated with the use of varenicline, a widely used smoking cessation
      drug. We conducted a systematic review and meta-analysis of randomized controlled
      trials to ascertain the serious adverse cardiovascular effects of varenicline
      compared with placebo among tobacco users. METHODS: We searched MEDLINE, EMBASE,
      the Cochrane Database of Systematic Reviews, websites of regulatory authorities
      and registries of clinical trials, with no date or language restrictions, through
      September 2010 (updated March 2011) for published and unpublished studies. We
      selected double-blind randomized controlled trials of at least one week's
      duration involving smokers or people who used smokeless tobacco that reported on
      cardiovascular events (ischemia, arrhythmia, congestive heart failure, sudden
      death or cardiovascular-related death) as serious adverse events asociated with
      the use of varenicline. RESULTS: We analyzed data from 14 double-blind randomized
      controlled trials involving 8216 participants. The trials ranged in duration from
      7 to 52 weeks. Varenicline was associated with a significantly increased risk of
      serious adverse cardiovascular events compared with placebo (1.06% [52/4908] in
      varenicline group v. 0.82% [27/3308] in placebo group; Peto odds ratio [OR] 1.72,
      95% confidence interval [CI] 1.09-2.71; I(2) = 0%). The results of various
      sensitivity analyses were consistent with those of the main analysis, and a
      funnel plot showed no publication bias. There were too few deaths to allow
      meaningful comparisons of mortality. INTERPRETATION: Our meta-analysis raises
      safety concerns about the potential for an increased risk of serious adverse
      cardiovascular events associated with the use of varenicline among tobacco users.

PMID- 21727229
TI  - Varenicline for smoking cessation: is it a heartbreaker?

PMID- 21727230
TI  - Being smarter with smartphones.

PMID- 21727232
TI  - Changes in neuropsychological functioning following treatment for late-life
      generalised anxiety disorder.
AB  - BACKGROUND: Generalised anxiety disorder (GAD) in older adults is associated with
      neuropsychological impairment. Aims We examined neuropsychological functioning in
      older adults with GAD in comparison with psychiatrically healthy older adults at
      baseline, and we examined changes following a 12-week placebo-controlled trial of
      escitalopram. METHOD: A total of 160 participants without dementia aged >=60 with
      current GAD and 37 individuals in a comparison group without psychiatric history
      underwent neuropsychological assessment. Of these, 129 participants with GAD were
      reassessed post-treatment (trial registration: NCT00105586). RESULTS: The
      participants with GAD performed worse than the comparison group in information
      processing speed, working memory, inhibition, problem-solving (including concept
      formation and mental flexibility) and immediate and delayed memory.
      Neuropsychological functioning was correlated with everyday functioning. After
      treatment, those with low cognitive scores experienced working memory, delayed
      memory and visuospatial ability improvement and those who reported clinical
      improvement in anxiety exhibited improvement in the ability to engage inhibition
      and episodic recall. These improvements were modest and of similar magnitude in
      both treatment conditions. CONCLUSIONS: Generalised anxiety disorder in older
      adults is associated with neuropsychological impairments, which are associated
      with functional impairment. Those with GAD who either have a low cognitive
      performance or report clinical improvement in anxiety post-treatment, show
      improvement in multiple cognitive domains. These findings underscore the
      importance of treatments that aid cognition as well as anxiety symptoms.

PMID- 21727233
TI  - Cognitive interpersonal maintenance model of eating disorders: intervention for
      carers.
AB  - BACKGROUND: Carers of people with eating disorders report high levels of
      distress. In addition, carers' responses to the illness may perpetuate eating
      disorder symptoms. A cognitive interpersonal maintenance model of eating
      disorders is proposed and interventions for carers may improve well-being in both
      carers and patients. Aims To examine an interpersonal maintenance model of eating
      disorders, using a self-help intervention for carers. METHOD: A pre-test-post
      test design was used with carers randomised into self-help or guided self-help,
      which included the Expert Carers Helping Others (ECHO) intervention. Carers'
      distress, well-being, proposed maintenance factors, and carer reports on the
      status of the patient were measured. RESULTS: Carers' distress reduced and
      secondary outcomes improved. Improvement in carers' status and perceived
      improvements in patients were associated with reductions in expressed emotion and
      in accommodating and enabling behaviours. Self-help and guided self-help versions
      were comparable. CONCLUSIONS: Changes in maintenance factors from the theoretical
      model were associated with a reduction in carers' distress and improvement in
      perceived patient functioning. Interventions which specifically target
      maintaining factors may be of benefit.

PMID- 21727234
TI  - Neural correlates of cognitive impairment in schizophrenia.
AB  - BACKGROUND: Cognitive impairment is an established feature of schizophrenia.
      However, little is known about its relationship to the structural and functional
      brain abnormalities that characterise the disorder. Aims To identify structural
      and/or functional brain abnormalities associated with schizophrenic cognitive
      impairment. METHOD: We carried out structural magnetic resonance imaging (MRI)
      and voxel-based morphometry in 26 participants who were cognitively impaired and
      23 who were cognitively preserved, all with schizophrenia, plus 39 matched
      controls. Nineteen of those who were cognitively impaired and 18 of those who
      were cognitively preserved plus 34 controls also underwent functional MRI during
      performance of a working memory task. RESULTS: No differences were found between
      the participants who were cognitively intact and those who were cognitively
      impaired in lateral ventricular volume or whole brain volume. Voxel-based
      morphometry also failed to reveal clusters of significant difference in grey and
      white matter volume between these two groups. However, during performance of the
      n-back task, the participants who were cognitively impaired showed hypoactivation
      compared with those who were cognitively intact in the dorsolateral prefrontal
      cortex among other brain regions. CONCLUSIONS: Cognitive impairment in
      schizophrenia is not a function of the structural brain abnormality that
      accompanies the disorder but has correlates in altered brain function.

PMID- 21727235
TI  - Antenatal depression and offspring psychopathology: the influence of childhood
      maltreatment.
AB  - BACKGROUND: Antenatal depression and childhood maltreatment have each been
      associated with offspring psychopathology, but have never been examined in the
      same sample. AIMS: To determine whether childhood maltreatment influences the
      association between antenatal depression and offspring psychopathology. METHOD:
      Prospectively collected data on antenatal depression, offspring maltreatment (age
      11) and offspring psychopathology (age 11 and 16) were analysed in 120 mother
      offspring dyads from the community-based South London Child Development Study.
      RESULTS: Antenatal depression increased the risk of maltreatment in the offspring
      by almost four times. Children exposed only to antenatal depression or only to
      childhood maltreatment were no more at risk of developing psychopathology;
      however, children exposed to both antenatal depression and childhood maltreatment
      were at almost 12 times greater risk of developing psychopathology than offspring
      not so exposed. CONCLUSIONS: Research investigating exposure to adverse events in
      utero and offspring psychopathology should take account of postnatal adverse
      events such as maltreatment.

PMID- 21727236
TI  - Hamstrings are most susceptible to injury during the late swing phase of
      sprinting.

PMID- 21727237
TI  - Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with enhanced cardiovascular
      (CV) risk and subclinical vascular disease. The proinflammatory milieu has been
      linked to premature atherosclerosis and endothelial dysfunction in RA. While
      interleukin 17 (IL-17) is considered pathogenic in RA, its role in determining
      vascular dysfunction in this disease has not been systematically assessed.
      OBJECTIVES: To analyse candidate variables that might determine endothelial
      function in various vascular territories in a cohort of patients with RA
      receiving treatment with biological agents, with minimal traditional CV risk
      factors and low disease activity score. METHODS: Patients with RA (n=50)
      receiving stable treatment with biological agents underwent measurement of
      conduit artery endothelial function by brachial artery flow-mediated dilatation;
      arterial compliance by pulse wave velocity (PWV) assessment; and endothelium
      dependent microvascular testing with Endo-Pat2000 device to assess the reactive
      hyperaemia index (RHI). IL-17 was quantified by ELISA and disease activity was
      assessed by 28-joint count Disease Activity Score. RESULTS: IL-17 was the main
      determinant of lower RHI in univariate and multivariate analysis. Traditional and
      non-traditional CV risk variables determined PWV, with a significant positive
      association with IL-17 in univariate and multivariate analysis. In contrast,
      conduit endothelial function was mainly determined by rheumatoid factor titres in
      univariate and multivariate analysis. Anti-cyclic citrullinated peptide titres,
      specific disease-modifying antirheumatic drugs or biological agents and disease
      activity did not determine vascular function. CONCLUSION: In patients with RA
      treated with biological agents, IL-17 is a main predictor of microvascular
      function and arterial compliance. This study suggests that IL-17 may play a
      significant role in development of endothelial dysfunction and cardiovascular
      disease in RA.

PMID- 21727238
TI  - Independent subtilases expansions in fungi associated with animals.
AB  - Many socially important fungi encode an elevated number of subtilisin-like serine
      proteases, which have been shown to be involved in fungal mutualisms with grasses
      and in parasitism of insects, nematodes, plants, other fungi, and mammalian skin.
      These proteins have endopeptidase activities and constitute a significant part of
      fungal secretomes. Here, we use comparative genomics to investigate the
      relationship between the quality and quantity of serine proteases and the ability
      of fungi to cause disease in invertebrate and vertebrate animals. Our screen of
      previously unexamined fungi allowed us to annotate and identify nearly 1000
      subtilisin-containing proteins and to describe six new categories of serine
      proteases. Architectures of predicted proteases reveal novel combinations of
      subtilisin domains with other, co-occurring domains. Phylogenetic analysis of the
      most common clade of fungal proteases, proteinase K, showed that gene family size
      changed independently in fungi, pathogenic to invertebrates (Hypocreales) and
      vertebrates (Onygenales). Interestingly, simultaneous expansions in the S8 and
      S53 families of subtilases in a single fungal species are rare. Our analysis
      finds that closely related systemic human pathogens may not show the same gene
      family expansions, and that related pathogens and nonpathogens may show the same
      type of gene family expansion. Therefore, the number of proteases does not appear
      to relate to pathogenicity. Instead, we hypothesize that the number of fungal
      serine proteases in a species is related to the use of the animal as a food
      source, whether it is dead or alive.

PMID- 21727239
TI  - Extensive chordate and annelid macrosynteny reveals ancestral homeobox gene
      organization.
AB  - Genes with the homeobox motif are crucial in developmental biology and widely
      implicated in the evolution of development. The Antennapedia (ANTP)-class is one
      of the two major classes of animal homeobox genes, and includes the Hox genes,
      renowned for their role in patterning the anterior-posterior axis of animals. The
      origin and evolution of the ANTP-class genes are a matter of some debate. A
      principal guiding hypothesis has been the existence of an ancient gene Mega
      cluster deep in animal ancestry. This hypothesis was largely established from
      linkage data from chordates, and the Mega-cluster hypothesis remains to be
      seriously tested in protostomes. We have thus mapped ANTP-class homeobox genes to
      the chromosome level in a lophotrochozoan protostome. Our comparison of gene
      organization in Platynereis dumerilii and chordates indicates that the Mega
      cluster, if it did exist, had already been broken up onto four chromosomes by the
      time of the protostome-deuterostome ancestor (PDA). These results not only
      elucidate an aspect of the genome organization of the PDA but also reveal high
      levels of macrosynteny between P. dumerilii and chordates. This implies a very
      low rate of interchromosomal genome rearrangement in the lineages leading to P.
      dumerilii and the chordate ancestor since the time of the PDA.

PMID- 21727240
TI  - Adolescent girls undergoing medical abortion have lower risk of haemorrhage,
      incomplete evacuation or surgical evacuation than women above 18 years old.

PMID- 21727241
TI  - Episodic physical and sexual activity increase risk for acute cardiac events.

PMID- 21727243
TI  - Restoring point-of-care testing during parathyroidectomy with a newer parathyroid
      hormone assay.
AB  - OBJECTIVE: Intraoperative parathyroid hormone (IOPTH) monitoring has emerged as a
      useful adjunct in parathyroidectomy. Originally performed within the operating
      room, removal of the Nichols assay from the market forced many surgeons to rely
      on testing done in central laboratories, reducing convenience and prolonging
      operative times. The authors hypothesized that PTH assessment with a newer point
      of-care (POC) assay would reduce results reporting time compared with central
      laboratory PTH assays. STUDY DESIGN: Cross-sectional study with planned data
      collection. SETTING: Academic medical center. SUBJECTS AND METHODS: Patients
      underwent parathyroidectomy for primary or recurrent hyperparathyroidism.
      Intraoperative monitoring of serum PTH levels was used to confirm biochemical
      cure following adenoma excision. Samples were run in duplicate using both a POC
      PTH assay (Future Diagnostics) located within the operating room and a laboratory
      based assay (Turbo PTH). Samples were taken at incision and at 5-, 10-, and 15
      minute intervals following removal of suspected parathyroid adenomas. Results
      reporting time was recorded and compared by nonparametric Wilcoxon rank sum test.
      RESULTS: Sixty-six serum samples were assayed. There was excellent correlation
      between POC and central-laboratory IOPTH results (r = 0.880, P < .001). The POC
      IOPTH results were available faster than corresponding central-laboratory
      results, with a mean of 14.4 minutes compared with 30.7 minutes, respectively (P
      < .001). All patients (100%) demonstrated a biochemical cure by the end of the
      procedure. CONCLUSION: Use of a rapid POC IOPTH assay results in a significant
      decrease in the amount of time for laboratory results to be communicated to the
      surgical team. This reduces operative times for parathyroidectomy and improves
      patient care.

PMID- 21727242
TI  - Diagnosis and management of ectopic pregnancy.

PMID- 21727244
TI  - Characterization and optimization of mTHPP nanoparticles for photodynamic therapy
      of head and neck cancer.
AB  - OBJECTIVES: To characterize the properties of polymeric micelles containing
      different loading percentages of mTHPP, a photosensitizer for photodynamic
      therapy (PDT), with respect to fluorescence, singlet oxygen ((1)O(2)) yield, and
      in vitro cytotoxicity in head and neck cancer cells. STUDY DESIGN: Laboratory
      study. SETTING: Polymer chemistry laboratory. SUBJECTS AND METHODS: Absorption
      and emission spectroscopy was used to characterize the mTHPP-loaded micelles. The
      (1)O(2) yield was measured to determine the efficiency of reactive oxygen species
      (ROS) generation. In vitro studies were conducted using the HN5 cells and
      confirmed with H2009 cells to determine the photodynamic efficacy. DNA assay and
      confocal microscopy was used to measure intracellular fluorescence. RESULTS: The
      mTHPP micelles demonstrated the highest fluorescence intensity at 0.5% loading.
      The (1)O(2) generation of the micelles in solution peaked at 2% loading.
      Phototoxicity and dark toxicity experiments in HN5 and H2009 cells demonstrated
      that the best therapeutic index was achieved with the 2% loaded micelles with
      100% cell cytotoxicity at a micelle concentration of 10 ug/mL and less than 10%
      dark cytotoxicity. In comparison, 10% loaded micelles demonstrated 100% cell
      cytotoxicity at a concentration of 20 ug/mL under both light and dark conditions.
      Confocal microscopy demonstrated increasing intracellular fluorescence with
      higher loading. CONCLUSIONS: The 2% mTHPP-loaded micelles generated greater
      (1)O(2), and 0.5% loading led to the most efficient generation of fluorescence in
      solution. Higher mTHPP loading density led to increased cellular fluorescence and
      dark cytotoxicity. Overall, 2% mTHPP-loaded micelles provided the optimal
      composition for photodynamic therapy with the largest therapeutic window.

PMID- 21727245
TI  - Superantigen-induced glucocorticoid insensitivity in the recurrence of chronic
      rhinosinusitis with nasal polyps.
AB  - OBJECTIVE: To investigate a potential mechanism by which superantigens could
      induce glucocorticoid insensitivity in chronic rhinosinusitis (CRS) patients.
      STUDY DESIGN: Prospective cohort study. SETTING: Tertiary medical center.
      SUBJECTS AND METHODS: Sinonasal polyps were obtained from CRS patients with nasal
      polyps (CRSwNP; 20 without recurrence, 18 with recurrent NP followed for 1.5-2.0
      years) and nasal mucosa from 16 CRS patients without nasal polyps (CRSsNP).
      Specimens were tested by enzyme-linked immunosorbent assay for staphylococcal
      exotoxins (SEs) including SEA, SEB, SEC, SED, and toxic shock syndrome toxin type
      1 (TSST-1) and assessed by immunohistochemistry for glucocorticoid receptor (GR)
      alpha and beta, and the GRbeta/GRalpha ratio was analyzed. RESULTS: In CRSwNP, 13
      of 18 (72.22%) subjects with subsequently recurrent NP, 11 of 20 (55.00%)
      subjects without NP recurrence, and 1 of 16 (6.25%) CRSsNP subjects with positive
      reactions for SEs were obtained. There were no positive results in controls. The
      expressions of GRbeta in 3 CRS groups and controls were significantly different
      (all P < .05), and a similar increasing tendency of the GRbeta/GRalpha ratio was
      found among groups besides the comparison of CRSwNP versus recurrent NP groups (P
      = .053). Furthermore, there was a clear trend of increased GRbeta expression in
      the enzyme-linked immunosorbent assay (ELISA)-positive samples compared with
      ELISA-negative samples. Concerning GRalpha, the expression was enhanced
      significantly just in toxin-positive recurrent NP versus controls (P = .048), but
      the relative induction of GRbeta was much higher, thereby leading to a higher
      GRbeta/GRalpha ratio. CONCLUSIONS: Bacterial superantigens may contribute to
      glucocorticoid insensitivity through induction of GRbeta, which appears to be a
      marker of steroid insensitivity in CRSwNP.

PMID- 21727246
TI  - Ethics: the joy of practice.
AB  - Dr John J. Conley was an integral part of the house of surgery in the latter part
      of the 20th century. Conley placed the ethical values of practice at the
      forefront of his teachings and transcribed many valuable lessons in his writings.
      In 1993, he wrote his version of the Hippocratic Oath outlining 12 important
      principles. Those principles are revisited here as a way to celebrate the joy of
      the calling that is medical practice. In addition, 7 new elements are added as a
      way to enhance that joy in the light of 21st-century medicine. The uplifting
      experience found in a career filled with ethical conduct is the legacy we should
      all strive to achieve.

PMID- 21727247
TI  - Antidepressant use during pregnancy and childhood autism spectrum disorders.
AB  - CONTEXT: The prevalence of autism spectrum disorders (ASDs) has increased over
      recent years. Use of antidepressant medications during pregnancy also shows a
      secular increase in recent decades, prompting concerns that prenatal exposure may
      contribute to increased risk of ASD. OBJECTIVE: To systematically evaluate
      whether prenatal exposure to antidepressant medications is associated with
      increased risk of ASD. DESIGN: Population-based case-control study. Medical
      records were used to ascertain case children and control children and to derive
      prospectively recorded information on mothers' use of antidepressant medications,
      mental health history of mothers, and demographic and medical covariates.
      SETTING: The Kaiser Permanente Medical Care Program in Northern California.
      PARTICIPANTS: A total of 298 case children with ASD (and their mothers) and 1507
      randomly selected control children (and their mothers) drawn from the membership
      of the Kaiser Permanente Medical Care Program in Northern California. MAIN
      OUTCOME MEASURES: ASDs. RESULTS: Prenatal exposure to antidepressant medications
      was reported for 20 case children (6.7%) and 50 control children (3.3%). In
      adjusted logistic regression models, we found a 2-fold increased risk of ASD
      associated with treatment with selective serotonin reuptake inhibitors by the
      mother during the year before delivery (adjusted odds ratio, 2.2 [95% confidence
      interval, 1.2-4.3]), with the strongest effect associated with treatment during
      the first trimester (adjusted odds ratio, 3.8 [95% confidence interval, 1.8
      7.8]). No increase in risk was found for mothers with a history of mental health
      treatment in the absence of prenatal exposure to selective serotonin reuptake
      inhibitors. CONCLUSION: Although the number of children exposed prenatally to
      selective serotonin reuptake inhibitors in this population was low, results
      suggest that exposure, especially during the first trimester, may modestly
      increase the risk of ASD. The potential risk associated with exposure must be
      balanced with the risk to the mother or fetus of untreated mental health
      disorders. Further studies are needed to replicate and extend these findings.

PMID- 21727248
TI  - Persistence of addictive disorders in a first-offender driving while impaired
      population.
AB  - CONTEXT: We compared the prevalence of alcohol use and other psychiatric
      disorders in offenders 15 years after a first conviction for driving while
      impaired with a general population sample. OBJECTIVE: To determine whether high
      rates of addictive and other psychiatric disorders previously demonstrated in
      this sample remain disproportionately higher compared with a matched general
      population sample. DESIGN: Point-in-time cohort study. SETTING: Pacific Institute
      for Research and Evaluation, Albuquerque, New Mexico. PARTICIPANTS: We
      interviewed convicted first offenders using the Composite International
      Diagnostic Interview 15 years after referral to a screening program in Bernalillo
      County, New Mexico. We calculated rates of diagnoses for non-Hispanic white and
      Hispanic women (n = 362) and men (n = 220) adjusting for missing data using
      multiple imputation and compared psychiatric diagnoses with findings from the
      National Comorbidity Survey Replication by sex and Hispanic ethnicity. RESULTS:
      Eleven percent of non-Hispanic white women and 12.8% of Hispanic women in the
      driving while impaired sample reported 12-month alcohol abuse or dependence,
      compared with 1.0% and 1.8%, respectively, in the National Comorbidity Survey
      Replication (comparison) sample. Almost 12% of non-Hispanic white men and 17.5%
      of Hispanic men in the driving while impaired sample reported 12-month alcohol
      abuse or dependence, compared with to 2.0% and 1.8%, respectively, in the
      comparison sample. These differences were statistically significant. Rates of
      drug use disorders and nicotine dependence were also elevated compared with the
      general population sample, while rates of major depressive disorder and
      posttraumatic stress disorder were similar. CONCLUSION: In this sample, high
      rates of addictive disorders persisted over 10 years among first offenders and
      greatly exceeded those found in a general population sample.

PMID- 21727249
TI  - Genetic heritability and shared environmental factors among twin pairs with
      autism.
AB  - CONTEXT: Autism is considered the most heritable of neurodevelopmental disorders,
      mainly because of the large difference in concordance rates between monozygotic
      and dizygotic twins. OBJECTIVE: To provide rigorous quantitative estimates of
      genetic heritability of autism and the effects of shared environment. DESIGN,
      SETTING, AND PARTICIPANTS: Twin pairs with at least 1 twin with an autism
      spectrum disorder (ASD) born between 1987 and 2004 were identified through the
      California Department of Developmental Services. MAIN OUTCOME MEASURES:
      Structured diagnostic assessments (Autism Diagnostic Interview-Revised and Autism
      Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance
      rates were calculated and parametric models were fitted for 2 definitions, 1
      narrow (strict autism) and 1 broad (ASD). RESULTS: For strict autism, probandwise
      concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence
      interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43);
      for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28
      0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the
      probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI,
      0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins,
      the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for
      13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in
      liability can be explained by shared environmental factors (55%; 95% CI, 9%-81%
      for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic
      heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD).
      CONCLUSION: Susceptibility to ASD has moderate genetic heritability and a
      substantial shared twin environmental component.

PMID- 21727250
TI  - Bruegel's Landscape With Fall of Icarus.

PMID- 21727252
TI  - Structural neuroimaging studies in major depressive disorder. Meta-analysis and
      comparison with bipolar disorder.
AB  - CONTEXT: Although differences in clinical characteristics exist between major
      depressive disorder (MDD) and bipolar disorder (BD), consistent structural brain
      abnormalities that distinguish the disorders have not been identified.
      OBJECTIVES: To investigate structural brain changes in MDD using meta-analysis of
      primary studies; assess the effects of medication, demographic, and clinical
      variables; and compare the findings with those of a meta-analysis of studies on
      BD. DATA SOURCES: The MEDLINE, EMBASE, and PsycINFO databases were searched for
      studies from January 1, 1980, to February 2, 2010. STUDY SELECTION: Two hundred
      twenty-five studies that used magnetic resonance imaging or x-ray computed
      tomography to compare brain structure in patients with MDD with that of controls
      were included in an online database, and 143 that measured common brain
      structures were selected for meta-analysis. DATA EXTRACTION: Twenty-five
      variables, including demographic and clinical data, were extracted from each
      study, when available. For the meta-analysis, mean structure size and standard
      deviation were extracted for continuous variables, and the proportion of patients
      and controls with an abnormality in brain structure was extracted for categorical
      variables. DATA SYNTHESIS: Compared with the structure of a healthy brain, MDD
      was associated with lateral ventricle enlargement; larger cerebrospinal fluid
      volume; and smaller volumes of the basal ganglia, thalamus, hippocampus, frontal
      lobe, orbitofrontal cortex, and gyrus rectus. Patients during depressive episodes
      had significantly smaller hippocampal volume than patients during remission.
      Compared with BD patients, those with MDD had reduced rates of deep white matter
      hyperintensities, increased corpus callosum cross-sectional area, and smaller
      hippocampus and basal ganglia. Both disorders were associated with increased
      lateral ventricle volume and increased rates of subcortical gray matter
      hyperintensities compared with healthy controls. CONCLUSIONS: The meta-analyses
      revealed structural brain abnormalities in MDD that are distinct from those
      observed in BD. These findings may aid investigators attempting to discriminate
      mood disorders using structural magnetic resonance imaging data.

PMID- 21727253
TI  - Cognitive therapy vs interpersonal psychotherapy in social anxiety disorder: a
      randomized controlled trial.
AB  - CONTEXT: Cognitive therapy (CT) focuses on the modification of biased information
      processing and dysfunctional beliefs of social anxiety disorder (SAD).
      Interpersonal psychotherapy (IPT) aims to change problematic interpersonal
      behavior patterns that may have an important role in the maintenance of SAD. No
      direct comparisons of the treatments for SAD in an outpatient setting exist.
      OBJECTIVE: To compare the efficacy of CT, IPT, and a waiting-list control (WLC)
      condition. DESIGN: Randomized controlled trial. SETTING: Two academic outpatient
      treatment sites. Patients  Of 254 potential participants screened, 117 had a
      primary diagnosis of SAD and were eligible for randomization; 106 participants
      completed the treatment or waiting phase. INTERVENTIONS: Treatment comprised 16
      individual sessions of either CT or IPT and 1 booster session. Twenty weeks after
      randomization, posttreatment assessment was conducted and participants in the WLC
      received 1 of the treatments. MAIN OUTCOME MEASURES: The primary outcome was
      treatment response on the Clinical Global Impression Improvement Scale as
      assessed by independent masked evaluators. The secondary outcome measures were
      independent assessor ratings using the Liebowitz Social Anxiety Scale, the
      Hamilton Rating Scale for Depression, and patient self-ratings of SAD symptoms.
      RESULTS: At the posttreatment assessment, response rates were 65.8% for CT, 42.1%
      for IPT, and 7.3% for WLC. Regarding response rates and Liebowitz Social Anxiety
      Scale scores, CT performed significantly better than did IPT, and both treatments
      were superior to WLC. At 1-year follow-up, the differences between CT and IPT
      were largely maintained, with significantly higher response rates in the CT vs
      the IPT group (68.4% vs 31.6%) and better outcomes on the Liebowitz Social
      Anxiety Scale. No significant treatment * site interactions were noted.
      CONCLUSIONS: Cognitive therapy and IPT led to considerable improvements that were
      maintained 1 year after treatment; CT was more efficacious than was IPT in
      reducing social phobia symptoms.

PMID- 21727251
TI  - Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in
      schizophrenia and genetic association with schizophrenia endophenotypes.
AB  - CONTEXT: Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan
      degradation, is an antagonist at N-methyl-d-aspartate and alpha7 nicotinic
      acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine
      signaling. Cortical kynurenic acid concentrations are elevated in the brain and
      cerebrospinal fluid of schizophrenia patients. The proximal cause may be an
      impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the
      branching point of the kynurenine pathway. OBJECTIVES: To examine KMO messenger
      RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye
      field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared
      with healthy control individuals and to explore the relationship between KMO
      single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes.
      DESIGN: Case-control postmortem and clinical study. SETTING: Maryland Brain
      Collection, outpatient clinics. PARTICIPANTS: Postmortem specimens from
      schizophrenia patients (n = 32) and control donors (n = 32) and a clinical sample
      of schizophrenia patients (n = 248) and healthy controls (n = 228). MAIN OUTCOME
      MEASURES: Comparison of quantitative KMO messenger RNA expression and KMO enzyme
      activity in postmortem FEF tissue between schizophrenia patients and controls and
      association of KMO single-nucleotide polymorphisms with messenger RNA expression
      in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth
      pursuit eye movements and oculomotor delayed response). RESULTS: In postmortem
      tissue, we found a significant and correlated reduction in KMO gene expression
      and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical
      sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but
      showed modest effects on predictive pursuit and visuospatial working memory
      endophenotypes. CONCLUSION: Our results provide converging lines of evidence
      implicating reduced KMO activity in the etiopathophysiology of schizophrenia and
      related neurocognitive deficits.

PMID- 21727254
TI  - The neurobiological role of the dorsolateral prefrontal cortex in recovery from
      trauma. Longitudinal brain imaging study among survivors of the South Korean
      subway disaster.
AB  - CONTEXT: A multiwave longitudinal neuroimaging study in a cohort of direct
      survivors of a South Korean subway disaster, most of whom recovered from
      posttraumatic stress disorder 5 years after trauma, provided a unique opportunity
      to investigate the brain correlates of recovery from a severe psychological
      trauma. OBJECTIVES: To investigate region-specific brain mobilization during
      successful recovery from posttraumatic stress disorder by assessing cortical
      thickness multiple times from early after trauma to recovery, and to examine
      whether a brain-derived neurotrophic factor gene polymorphism was associated with
      this brain mobilization. DESIGN: Five-year follow-up case-control study conducted
      from 2003-2007. SETTING: Seoul National University and Hospital. PARTICIPANTS:
      Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched
      control group members recruited from the disaster registry and local community,
      respectively, who contributed 156 high-resolution brain magnetic resonance images
      during 3 waves of assessments. MAIN OUTCOME MEASURES: Cerebral cortical thickness
      measured in high-resolution anatomic magnetic resonance images using a validated
      cortical thickness analysis tool and its prospective changes from early after
      trauma to recovery in trauma-exposed individuals and controls. RESULTS: Trauma
      exposed individuals had greater dorsolateral prefrontal cortical (DLPFC)
      thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal
      cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P <= .01])
      relative to controls. Thicknesses gradually normalized over time during recovery.
      We found a positive linear trend, with trauma-exposed individuals with a
      valine/valine genotype having the greatest DLPFC cortical thickness, followed by
      those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC
      thickness was associated with greater posttraumatic stress disorder symptom
      reductions and better recovery. CONCLUSION: The DLPFC region might play an
      important role in psychological recovery from a severely traumatic event in
      humans.

PMID- 21727255
TI  - Mortality rates in patients with anorexia nervosa and other eating disorders. A
      meta-analysis of 36 studies.
AB  - CONTEXT: Morbidity and mortality rates in patients with eating disorders are
      thought to be high, but exact rates remain to be clarified. OBJECTIVE: To
      systematically compile and analyze the mortality rates in individuals with
      anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise
      specified (EDNOS). DATA SOURCES: A systematic literature search, appraisal, and
      meta-analysis were conducted of the MEDLINE/PubMed, PsycINFO, and Embase
      databases and 4 full-text collections (ie, ScienceDirect, Ingenta Select, Ovid,
      and Wiley-Blackwell Interscience). STUDY SELECTION: English-language, peer
      reviewed articles published between January 1, 1966, and September 30, 2010, that
      reported mortality rates in patients with eating disorders. DATA EXTRACTION:
      Primary data were extracted as raw numbers or confidence intervals and corrected
      for years of observation and sample size (ie, person-years of observation).
      Weighted proportion meta-analysis was used to adjust for study size using the
      DerSimonian-Laird model to allow for heterogeneity inclusion in the analysis.
      DATA SYNTHESIS: From 143 potentially relevant articles, we found 36 quantitative
      studies with sufficient data for extraction. The studies reported outcomes of AN
      during 166 642 person-years, BN during 32 798 person-years, and EDNOS during 22
      644 person-years. The weighted mortality rates (ie, deaths per 1000 person-years)
      were 5.1 for AN, 1.7 for BN, and 3.3 for EDNOS. The standardized mortality ratios
      were 5.86 for AN, 1.93 for BN, and 1.92 for EDNOS. One in 5 individuals with AN
      who died had committed suicide. CONCLUSIONS: Individuals with eating disorders
      have significantly elevated mortality rates, with the highest rates occurring in
      those with AN. The mortality rates for BN and EDNOS are similar. The study found
      age at assessment to be a significant predictor of mortality for patients with
      AN. Further research is needed to identify predictors of mortality in patients
      with BN and EDNOS.

PMID- 21727256
TI  - Neonatal head ultrasound abnormalities in preterm infants and adolescent
      psychiatric disorders.
AB  - CONTEXT: Infants born prematurely are at risk for a perinatal encephalopathy
      characterized by white and gray matter injuries that affect subsequent cortical
      development and neural connectivity and potentially increase risk for later
      psychiatric disorder. OBJECTIVE: To determine the relation of perinatal brain
      injury, as detected by neonatal head ultrasound, to psychiatric disorders in
      adolescents who were born prematurely. DESIGN: Prospective cohort. SETTING:
      Community. PARTICIPANTS: Adolescent survivors of a population-based low-birth
      weight (<2000 g; 96% preterm; born 1984-1987) cohort (n = 1105) screened as
      neonates with serial head ultrasounds. Neonatal head ultrasound abnormalities
      were categorized as either (1) germinal matrix and/or intraventricular hemorrhage
      or (2) parenchymal lesions and/or ventricular enlargement. Of 862 eligible
      survivors, 628 (72.9%) were assessed at age 16 years. The sample consisted of 458
      nondisabled survivors assessed in person. Main Outcome Measure  Adolescent
      current and lifetime psychiatric disorders assessed with parent report on the
      Diagnostic Interview Schedule for Children-IV. RESULTS: Compared with no
      abnormality, germinal matrix/intraventricular hemorrhage increased risk for
      current major depressive disorder (odds ratio, 2.7; 95% confidence interval, 1.0
      6.8) and obsessive-compulsive disorder (9.5; 3.0-30.1). Parenchymal
      lesions/ventricular enlargement increased risk for current attention
      deficit/hyperactivity disorder-inattentive type (odds ratio, 7.6; 95% confidence
      interval, 2.0-26.5), tic disorders (8.4; 2.4-29.6), and obsessive-compulsive
      disorder (7.6; 1.39-42.0). Parenchymal lesions/ventricular enlargement were not
      related to lifetime attention-deficit/hyperactivity disorder-inattentive type,
      but all other relations were similar for lifetime disorders. Control for other
      early risk factors did not alter these relations. Most of these relations
      persisted with control for concurrent cognitive or motor problems. CONCLUSION: In
      preterm infants, 2 distinct types of perinatal brain injury detectable with
      neonatal head ultrasound selectively increase risk in adolescence for psychiatric
      disorders in which dysfunction of subcortical-cortical circuits has been
      implicated.

PMID- 21727257
TI  - Family study of borderline personality disorder and its sectors of
      psychopathology.
AB  - CONTEXT: The familiality of borderline personality disorder (BPD) and its sectors
      of psychopathology are incompletely understood. OBJECTIVES: To assess the
      familial aggregation of BPD and its 4 major sectors (affective, interpersonal,
      behavioral, and cognitive) and test whether the relationship of the familial and
      nonfamilial associations among these sectors can be accounted for by a latent BPD
      construct. DESIGN: Family study, with direct interviews of probands and
      relatives. SETTING: A psychiatric hospital (McLean Hospital) and the Boston-area
      community. PARTICIPANTS: A total of 368 probands (132 with BPD, 134 without BPD,
      and 102 with major depressive disorder) and 885 siblings and parents of probands.
      MAIN ASSESSMENTS: The Diagnostic Interview for DSM-IV Personality Disorders and
      the Revised Diagnostic Interview for Borderlines (DIB-R) were used to assess
      borderline psychopathology, and the Structured Clinical Interview for DSM-IV was
      used to assess major depressive disorder. RESULTS: Borderline personality
      disorder meeting both DSM-IV and DIB-R criteria showed substantial familial
      aggregation for BPD in individuals with a family member with BPD vs those without
      a family member with BPD, using proband-relative pairs (risk ratio, 2.9; 95%
      confidence interval, 1.5-5.5) as well as using all pairs of family members (3.9;
      1.7-9.0). All 4 sectors of BPD psychopathology aggregated significantly in
      families, using both DSM-IV and DIB-R definitions (correlation of traits among
      all pairs of family members ranged from 0.07 to 0.27), with the affective and
      interpersonal sectors showing the highest levels; however, the level of familial
      aggregation of BPD was higher than that of the individual sectors. The
      relationship among the sectors was best explained by a common pathway model in
      which the sectors represent manifestations of a latent BPD construct.
      CONCLUSIONS: Familial factors contribute to BPD and its sectors of
      psychopathology. Borderline personality disorder may arise from a unitary
      liability that finds expression in its sectors of psychopathology.

PMID- 21727258
TI  - Deployment and mental health diagnoses among children of US Army personnel.
AB  - OBJECTIVE: To characterize the risk of mental health diagnoses among children of
      US military personnel associated with parental deployment in support of Operation
      Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). DESIGN: Nonrandomized,
      retrospective cohort study (2003-2006). SETTING: Electronic medical record data
      for outpatient care. PARTICIPANTS: Children (N = 307 520) aged 5 to 17 years with
      at least 1 active-duty US Army parent. MAIN EXPOSURE: Number of months of
      parental deployment for OIF and OEF. MAIN OUTCOME MEASURES: A mental health
      diagnosis was defined as having at least 1 mental health-related International
      Classification of Diseases, Ninth Revision, code out of 4 possible codes for a
      given outpatient medical visit. Diagnoses were further classified into 1 of 17
      disorder categories. RESULTS: Overall, children with parental deployment
      represented an excess of 6579 mental health diagnoses during the 4-year period
      compared with children whose parents did not deploy. After the children's age,
      sex, and mental health history were adjusted for, excess mental health diagnoses
      associated with parental deployment were greatest for acute stress
      reaction/adjustment, depressive, and pediatric behavioral disorders and increased
      with total months of parental deployment. Boys and girls showed similar patterns
      within these same categories, with more diagnoses observed in older children
      within sex groups and in boys relative to girls within age groups. CONCLUSIONS: A
      dose-response pattern between deployment of a parent for OIF and OEF and
      increased mental health diagnoses was observed in military children of all ages.
      Findings may be used to inform policy, prevention, and treatment efforts for
      military families facing substantial troop deployments.

PMID- 21727259
TI  - Recidivism in the child protection system: identifying children at greatest risk
      of reabuse among those remaining in the home.
AB  - OBJECTIVE: To identify risk clusters that are associated with higher or lower
      risk of new abuse reports (rereports) and substantiated rereports (reabuse) in
      children who remain in the home after an abuse report. DESIGN: A 5-year
      prospective cohort study. SETTING: National Survey of Child and Adolescent Well
      Being. PARTICIPANTS: Children reported to the child protection system for child
      abuse. MAIN EXPOSURE: Remaining in the home after an abuse report. MAIN OUTCOME
      MEASURE: Incidence of rereports and reabuse. RESULTS: A total of 2578 children
      remained in the home following an abuse report, and 44% were rereported within
      the follow-up period. In bivariate analyses, children with behavior problems (49%
      vs 38%), caregivers with an abuse history (33% vs 16%) or a child welfare history
      (38% vs 25%), and families with an annual income lower than $20 000 (70% vs 60%)
      were more likely to be rereported. Forty-five percent of rereports were
      substantiated reabuse, but 2 risk clusters had a higher incidence: (1) the
      cluster with a substantiated index report, having a caregiver without parenting
      class, non-African American race/ethnicity, and caregiver younger than 41.5 years
      (54%); and (2) the cluster with a substantiated index report, a caregiver with
      parenting class, and child age younger than 8.5 years (60%). The lowest risk
      group for reabuse had a substantiated index report, a caregiver without parenting
      class, non-African American race/ethnicity, and a caregiver 41.5 years or older
      (26%). CONCLUSIONS: Among children remaining in the home following an abuse
      report, specific risk groups have higher and lower incidence of rereports and
      reabuse. These risk-group categories may be useful to child protection services
      and others in identifying at-risk children and making decisions about placement
      and services.

PMID- 21727260
TI  - Effectiveness of interventions aimed at reducing screen time in children: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the impact of interventions focused on reducing screen
      time. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled
      Trials, PsycINFO, ERIC, and CINAHL through April 21, 2011. STUDY SELECTION:
      Included studies were randomized controlled trials of children aged 18 years or
      younger with interventions that focused on reducing screen time. INTERVENTION:
      Efforts to reduce screen time. MAIN OUTCOME MEASURES: The primary outcome was
      body mass index (BMI); the secondary outcome was screen time (hours per week).
      RESULTS: A total of 1120 citations were screened, and 13 studies were included in
      the systematic review. Study samples ranged in age (3.9-11.7 years) and size (21
      1295 participants). Interventions ranged in length (1-24 months) and recruitment
      location (5 in schools, 2 in medical clinics, 1 in a community center, and 5 from
      the community). For the primary outcome, the meta-analysis included 6 studies,
      and the difference in mean change in BMI in the intervention group compared with
      the control group was -0.10 (95% confidence interval [CI], -0.28 to 0.09) (P =
      .32). The secondary outcome included 9 studies, and the difference in mean change
      from baseline in the intervention group compared with the control group was -0.90
      h/wk (95% CI, -3.47 to 1.66 h/wk) (P = .49). A subgroup analysis of preschool
      children showed a difference in mean change in screen time of -3.72 h/wk (95% CI,
      -7.23 to -0.20 h/wk) (P = .04). CONCLUSIONS: Our systematic review and meta
      analysis did not demonstrate evidence of effectiveness of interventions aimed at
      reducing screen time in children for reducing BMI and screen time. However,
      interventions in the preschool age group hold promise.

PMID- 21727261
TI  - Children of military service members: raising national awareness of the family
      health consequences of combat deployment.

PMID- 21727262
TI  - School-based body mass index screening and parent notification: a statewide
      natural experiment.
AB  - OBJECTIVE: To assess the impact of body mass index (BMI) screening with parental
      notification on weight status for California public school students. DESIGN: A
      natural experiment wherein nearly all California school districts conducted
      annual BMI screening in the fifth, seventh, and ninth grades, but parental
      notification of BMI screening results was optional. SETTING: Data from mandatory
      fitness testing in California public schools for 2001 through 2008. PARTICIPANTS:
      A total of 6 967 120 fifth-, seventh-, and ninth-grade youth (73% of enrolled
      students). INTERVENTION: School-based BMI screening with optional parent
      notification. MAIN OUTCOME MEASURE: Body mass index z score was the main outcome
      in adjusted mixed-effects linear regression models, assessing whether notifying
      parents of their child's BMI in a given year predicted BMI z score 2 years hence.
      RESULTS: Rates of parental notification of BMI screening results increased from
      35% in 2001 to 52% in 2008. Body mass index notification in fifth and/or seventh
      grade had no impact on subsequent BMI z scores (95% confidence interval, -0.03 to
      0.01) compared with no notification. No differences in the impact of notification
      were seen by race/ethnicity. Results did not vary with sensitivity analyses.
      CONCLUSIONS: These findings suggest that while BMI screening itself could have
      benefits, parental notification in its current form may not reduce pediatric
      obesity. Until effective methods of notification are identified, schools should
      consider directing resources to policies and programs proven to improve student
      health.

PMID- 21727263
TI  - Clinical Reasoning: An encephalopathic 3-day-old infant.

PMID- 21727264
TI  - Teaching NeuroImages: Glutaric aciduria type 1 (glutaryl-CoA dehydrogenase
      deficiency).

PMID- 21727267
TI  - Opioid withdrawal due to Twiddler syndrome.

PMID- 21727268
TI  - Licorice-associated reversible cerebral vasoconstriction with PRES.

PMID- 21727269
TI  - Sensory ganglionopathy due to gluten sensitivity.

PMID- 21727270
TI  - Hidden in the sixties: newborn screening programs and state authority.

PMID- 21727271
TI  - Arguments for and against standardized mean differences (effect sizes).

PMID- 21727272
TI  - Physical activity awareness of British adolescents.
AB  - OBJECTIVES: To assess adolescent physical activity (PA) awareness and to
      investigate associations with biologic and psychosocial factors. DESIGN: Cross
      sectional study from November 1, 2005, through July 31, 2007 (the ROOTS study).
      SETTING: Population-based sample recruited from Cambridgeshire and Suffolk
      schools (United Kingdom). PARTICIPANTS: Of 799 participants, 43.6% were male. The
      mean (SD) age was 14.5 (0.5) years. MAIN EXPOSURES: Self-rated PA perception,
      self-reported psychosocial factors, and measured anthropometry. MAIN OUTCOME
      MEASURES: We measured PA with accelerometry for 5 days. Inactive was defined as
      less than 60 minutes per day of moderate and vigorous PA (MVPA) measured by
      accelerometry. Associations between awareness (agreement between self-rated and
      accelerometry-measured active/inactive) and potential correlates were
      investigated using multinomial logistic regression. RESULTS: Approximately 70.1%
      of adolescents were inactive (81.2% of girls and 55.8% of boys; odds ratio [OR],
      3.41; 95% confidence interval [CI], 2.41-4.82). There were 52.6% of all girls
      (64.8% of inactive girls) and 33.6% of all boys (60.3% of inactive boys) who
      inaccurately rated themselves as active (overestimators). Compared with girls
      accurately describing themselves as inactive (28.6%), girl overestimators had
      lower fat mass (OR, 0.84; 95% CI, 0.70-0.99), higher socioeconomic status (high
      vs low OR, 2.38; 95% CI, 1.07-5.32), more parent support (OR, 1.57; 95% CI, 1.12
      2.22), and better family relationships (OR, 0.25; 95% CI, 0.09- 0.67). Among boys
      accurately describing themselves as inactive (22.1%), overestimators had lower
      fat mass (OR, 0.86; 95% CI, 0.77-0.96) and reported more peer support (OR, 1.75;
      95% CI, 1.32-2.30) and less teasing (OR, 0.75; 95% CI, 0.61-0.92). CONCLUSIONS: A
      substantial number of adolescents believe themselves to be more physically active
      than they really are. They may be unaware of potential health risks and unlikely
      to participate in PA promotion programs. Increasing information of PA health
      benefits beyond weight control might encourage behavior change.

PMID- 21727273
TI  - Prediction of adolescents' glycemic control 1 year after diabetes-specific family
      conflict: the mediating role of blood glucose monitoring adherence.
AB  - OBJECTIVE: To test adherence to blood glucose monitoring (BGM) as a mediator
      between diabetes-specific family conflict and glycemic control (hemoglobin A(1c)
      [HbA(1c)] levels) for 1 year. DESIGN: Three waves of prospective data spanning 1
      year. SETTING: Diabetes clinic in a large tertiary care children's hospital in
      the Midwestern United States. PARTICIPANTS: One hundred forty-five dyads composed
      of an adolescent (aged 13-18 years) with type 1 diabetes mellitus and a parent.
      MAIN EXPOSURES: Adolescent- and parent-rated diabetes-specific family conflict
      and mean daily BGM frequency obtained through meter downloads. MAIN OUTCOME
      MEASURE: Levels of HbA(1c), abstracted from the medical record. RESULTS: In
      separate general linear models, higher adolescent-rated family conflict scores at
      baseline predicted less frequent BGM at 6 months (beta = -0.08 [P = .01]) and
      higher HbA(1c) levels at 12 months (beta = 0.08 [P = .02]). In the multivariate
      model including baseline conflict and BGM as predictors of HbA(1c) levels, BGM
      was a significant predictor (beta = -0.24 [P = .007]) and conflict was no longer
      significant (beta = 0.05 [P = .11]), supporting the mediation hypothesis. Post
      hoc probing showed that BGM explained 24% of the variance in the conflict-HbA(1c)
      link. The mediation between parent-reported conflict and HbA(1c) levels via BGM
      adherence was partially supported (conflict predicting HbA(1c) in the zero-order
      equation, beta = -0.24 [P = .004]; multivariate equation, beta = 0.06 [P = .02]),
      and BGM frequency explained 16% of the conflict-HbA(1c) link. CONCLUSIONS:
      Diabetes-specific family conflict in adolescence predicts deteriorations in BGM
      and subsequent glycemic control for at least 1 year. Results support ongoing
      intervention research designed to reduce family conflict and thus prevent a
      trajectory of declining adherence and glycemic control across adolescence.

PMID- 21727274
TI  - How infants die in the neonatal intensive care unit: trends from 1999 through
      2008.
AB  - OBJECTIVE: To determine whether trends toward decreasing use of cardiopulmonary
      resuscitation at the time of death and increasing frequency of forgoing life
      sustaining treatment had continued, as few studies quantifying mode of death for
      hospitalized infants have been conducted in the last 10 years. DESIGN:
      Retrospective descriptive study. SETTING: Regional referral neonatal intensive
      care unit. PARTICIPANTS: Infants who died from January 1, 1999, to December 31,
      2008. Infants were categorized into following categories: (1) very preterm (<=32
      weeks' gestation); (2) congenital anomaly; and (3) other. MAIN OUTCOME MEASURES:
      The primary outcome was level of clinical service provided at the end of life
      (care withheld, care withdrawn, or full resuscitation). RESULTS: For 10 years,
      414 neonatal patients died. Of these, 61.6% had care withdrawn, 20.8% had care
      withheld, and 17.6% received cardiopulmonary resuscitation. The percentage of
      deaths that followed withholding of treatment rose by 1% per year (P = .01). Most
      of this change was accounted for by withholding of therapy in the very premature
      group. CONCLUSION: During the 10-year period, the primary mode of death in this
      regional referral neonatal intensive care unit was withdrawal of life-sustaining
      support. When death is imminent or medical care is considered futile, the
      approach is thought to provide a peaceful, controlled setting. Significant
      increase in withholding of care suggests improved recognition of medical futility
      and desire to provide a peaceful death.

PMID- 21727275
TI  - Sterile cerebrospinal fluid pleocytosis in young febrile infants with urinary
      tract infections.
AB  - OBJECTIVES: To determine the prevalence of and to identify risk factors for
      sterile cerebrospinal fluid (CSF) pleocytosis in a large sample of febrile young
      infants with urinary tract infections (UTIs) and to describe the clinical courses
      of those patients. DESIGN: Secondary analysis of a multicenter retrospective
      review. SETTING: Emergency departments of 20 North American hospitals. Patients
      Infants aged 29 to 60 days with temperatures of 38.0 degrees C or higher and
      culture-proven UTIs who underwent a nontraumatic lumbar puncture from January 1,
      1995, through May 31, 2006. MAIN EXPOSURE: Febrile UTI. OUTCOME MEASURES:
      Presence of sterile CSF pleocytosis defined as CSF white blood cell count of
      10/MUL or higher in the absence of bacterial meningitis and clinical course and
      treatment (ie, presence of adverse events, time to defervescence, duration of
      parenteral antibiotic treatment, and length of hospitalization). RESULTS: A total
      of 214 of 1190 infants had sterile CSF pleocytosis (18.0%; 95% confidence
      interval, 15.9%-20.3%). Only the peripheral white blood cell count was
      independently associated with sterile CSF pleocytosis, and patients with a
      peripheral white blood cell count of 15/MUL or higher had twice the odds of
      having sterile CSF pleocytosis (odds ratio, 1.97; 95% confidence interval, 1.32
      2.94; P = .001). In the subset of patients at very low risk for adverse events
      (ie, not clinically ill in the emergency department and without a high-risk
      medical history), patients with and without sterile CSF pleocytosis had similar
      clinical courses; however, patients with CSF pleocytosis had longer parenteral
      antibiotics courses (median length, 4 days [interquartile range, 3-6 days] vs 3
      days [interquartile range, 3-5 days]) (P = .04). CONCLUSION: Sterile CSF
      pleocytosis occurs in 18% of young infants with UTIs. Patients with CSF
      pleocytosis at very low risk for adverse events may not require longer treatment
      with antibiotics.

PMID- 21727277
TI  - Infant pertussis epidemiology and implications for tetanus toxoid, reduced
      diphtheria toxoid, and acellular pertussis (Tdap) vaccination: King County,
      Washington, 2002 through 2007.
AB  - OBJECTIVES: To describe the epidemiology of infant pertussis in King County,
      Washington, and to better understand the implications for tetanus toxoid, reduced
      diphtheria toxoid, and acellular pertussis (Tdap) vaccination among older
      children, adolescents, and adults. DESIGN: Retrospective analysis of reported
      pertussis cases among infants younger than 1 year, January 1, 2002, through
      December 31, 2007. SETTING: King County, Washington. PARTICIPANTS: Reported
      pertussis cases among infants younger than 1 year between 2002 and 2007. MAIN
      OUTCOME MEASURES: Bordetella pertussis from a household member or close contact
      was the primary exposure. The main outcome measures were age and vaccination
      status, incidence by race/ethnicity, suspected exposure, and Tdap eligibility of
      household members and close contacts. RESULTS: Among 176 confirmed cases of
      infants with pertussis, the median age was 3 months (age range, 0-11 months);
      80.1% were younger than 6 months. Seventy-seven percent were age-appropriately
      vaccinated. Between 2002 and 2007, the overall mean annual incidence was 136
      cases per 100,000 infant population. Compared with a mean annual incidence of 73
      cases per 100,000 infant population among whites, the incidence was 246 cases per
      100,000 infant population among blacks (rate ratio [RR], 3.37; 95% confidence
      interval [CI], 2.59-4.44) and 194 cases per 100,000 infant population among
      Hispanics (RR, 2.66; 95% CI, 2.02-3.53). Households were the suspected exposure
      location for 70.0% of cases. Case households had a median of 3 (range, 1-15) Tdap
      eligible persons. CONCLUSIONS: The burden of infant pertussis in King County,
      Washington, was high between 2002 and 2007, especially among racial/ethnic
      minorities. Tdap vaccination of eligible household members and close contacts
      should be promoted as an additional means of protecting infants from pertussis.

PMID- 21727278
TI  - Development in toddlers with and without deformational plagiocephaly.
AB  - OBJECTIVE: To determine whether the heightened risk of developmental delays seen
      in infancy in patients with deformational plagiocephaly (DP) continues into the
      toddler years. DESIGN: Longitudinal study comparing the development of children
      with and without DP, with assessments in infancy (mean age, 7 months) and at age
      18 months. SETTING: Infants with DP were recruited from a large craniofacial
      center, and unaffected infants were recruited from a research registry.
      PARTICIPANTS: The study included 227 children with DP and 232 children without
      previously diagnosed DP. MAIN EXPOSURE: Diagnosis of DP by a craniofacial
      specialist. MAIN OUTCOME MEASURES: Bayley Scales of Infant and Toddler
      Development, Third Edition, scores. RESULTS: Toddlers with DP scored lower than
      did unaffected children on all the scales of the Bayley Scales of Infant and
      Toddler Development, Third Edition. Motor score differences were smaller and
      cognitive and language score differences were greater than those observed in
      infancy. CONCLUSIONS: Toddlers with DP continue to exhibit evidence of
      developmental delays relative to toddlers without DP. These findings do not
      necessarily imply a causal relationship between DP and development because
      children with delays may be more likely to develop DP. Nonetheless, it seems that
      increased developmental surveillance is warranted in this population.

PMID- 21727279
TI  - Picture of the month--quiz case. Crohn disease.

PMID- 21727276
TI  - Effects of prophylactic indomethacin in extremely low-birth-weight infants with
      and without adequate exposure to antenatal corticosteroids.
AB  - OBJECTIVE: To examine whether treatment with antenatal corticosteroids modifies
      the immediate and long-term effects of prophylactic indomethacin sodium
      trihydrate in extremely low-birth-weight infants. DESIGN: Post hoc subgroup
      analysis of data from the Trial of Indomethacin Prophylaxis in Preterms. SETTING:
      Thirty-two neonatal intensive care units in Canada, the United States, Australia,
      New Zealand, and Hong Kong. PARTICIPANTS: A total of 1195 infants with birth
      weights of 500 to 999 g and known exposure to antenatal corticosteroids. We
      defined as adequate any exposure to antenatal corticosteroids that occurred at
      least 24 hours before delivery. INTERVENTION: Indomethacin or placebo
      intravenously once daily for the first 3 days. OUTCOME MEASURES: Death or
      survival to 18 months with cerebral palsy, cognitive delay, severe hearing loss,
      or bilateral blindness; severe periventricular and intraventricular hemorrhage;
      patent ductus arteriosus; and surgical closure of a patent ductus arteriosus.
      RESULTS: Of the 1195 infants in this analysis cohort, 670 had adequate and 525
      had inadequate exposure to antenatal corticosteroids. There was little
      statistical evidence of heterogeneity in the effects of prophylactic indomethacin
      between the subgroups for any of the outcomes. The adjusted P values for
      interaction were as low as .15 for the outcome of death or impairment at 18
      months and as high as .80 for the outcome of surgical duct closure. CONCLUSION:
      We find little evidence that the effects of prophylactic indomethacin vary in
      extremely low-birth-weight infants with and without adequate exposure to
      antenatal corticosteroids. Trial Registration clinicaltrials.gov Identifier:
      NCT00009646.

PMID- 21727281
TI  - How to measure secondhand smoke exposure in a pediatric clinic setting.

PMID- 21727282
TI  - Reference range for cerebrospinal fluid protein concentration in children and
      adolescents.

PMID- 21727283
TI  - Access to autism evaluation appointments with developmental-behavioral and
      neurodevelopmental subspecialists.

PMID- 21727284
TI  - Alcohol brand preference and binge drinking among adolescents.

PMID- 21727285
TI  - Media influence on adolescent alcohol use.

PMID- 21727286
TI  - Summaries for patients. A comparison of massage therapy and usual medical care
      for chronic low back pain.

PMID- 21727287
TI  - In the clinic. Osteoporosis.

PMID- 21727288
TI  - A comparison of the effects of 2 types of massage and usual care on chronic low
      back pain: a randomized, controlled trial.
AB  - BACKGROUND: Few studies have evaluated the effectiveness of massage for chronic
      low back pain. OBJECTIVE: To compare the effectiveness of 2 types of massage and
      usual care for chronic back pain. DESIGN: Parallel-group randomized, controlled
      trial. Randomization was computer-generated, with centralized allocation
      concealment. Participants were blinded to massage type but not to assignment to
      massage versus usual care. Massage therapists were unblinded. The study personnel
      who assessed outcomes were blinded to treatment assignment. (ClinicalTrials.gov
      registration number: NCT00371384) SETTING: An integrated health care delivery
      system in the Seattle area. PATIENTS: 401 persons 20 to 65 years of age with
      nonspecific chronic low back pain. INTERVENTION: Structural massage (n = 132),
      relaxation massage (n = 136), or usual care (n = 133). MEASUREMENTS: Roland
      Disability Questionnaire (RDQ) and symptom bothersomeness scores at 10 weeks
      (primary outcome) and at 26 and 52 weeks (secondary outcomes). Mean group
      differences of at least 2 points on the RDQ and at least 1.5 points on the
      symptom bothersomeness scale were considered clinically meaningful. RESULTS: The
      massage groups had similar functional outcomes at 10 weeks. The adjusted mean RDQ
      score was 2.9 points (95% CI, 1.8 to 4.0 points) lower in the relaxation group
      and 2.5 points (CI, 1.4 to 3.5 points) lower in the structural massage group than
      in the usual care group, and adjusted mean symptom bothersomeness scores were 1.7
      points (CI, 1.2 to 2.2 points) lower with relaxation massage and 1.4 points (CI,
      0.8 to 1.9 points) lower with structural massage. The beneficial effects of
      relaxation massage on function (but not on symptom reduction) persisted at 52
      weeks but were small. LIMITATION: Participants were not blinded to treatment.
      CONCLUSION: Massage therapy may be effective for treatment of chronic back pain,
      with benefits lasting at least 6 months. No clinically meaningful difference
      between relaxation and structural massage was observed in terms of relieving
      disability or symptoms. PRIMARY FUNDING SOURCE: National Center for Complementary
      and Alternative Medicine.

PMID- 21727289
TI  - Personalizing mammography by breast density and other risk factors for breast
      cancer: analysis of health benefits and cost-effectiveness.
AB  - BACKGROUND: Current guidelines recommend mammography every 1 or 2 years starting
      at age 40 or 50 years, regardless of individual risk for breast cancer.
      OBJECTIVE: To estimate the cost-effectiveness of mammography by age, breast
      density, history of breast biopsy, family history of breast cancer, and screening
      interval. DESIGN: Markov microsimulation model. DATA SOURCES: Surveillance,
      Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and
      the medical literature. TARGET POPULATION: U.S. women aged 40 to 49, 50 to 59, 60
      to 69, and 70 to 79 years with initial mammography at age 40 years and breast
      density of Breast Imaging Reporting and Data System (BI-RADS) categories 1 to 4.
      TIME HORIZON: Lifetime. PERSPECTIVE: National health payer. INTERVENTION:
      Mammography annually, biennially, or every 3 to 4 years or no mammography.
      OUTCOME MEASURES: Costs per quality-adjusted life-year (QALY) gained and number
      of women screened over 10 years to prevent 1 death from breast cancer. RESULTS OF
      BASE-CASE ANALYSIS: Biennial mammography cost less than $100,000 per QALY gained
      for women aged 40 to 79 years with BI-RADS category 3 or 4 breast density or aged
      50 to 69 years with category 2 density; women aged 60 to 79 years with category 1
      density and either a family history of breast cancer or a previous breast biopsy;
      and all women aged 40 to 79 years with both a family history of breast cancer and
      a previous breast biopsy, regardless of breast density. Biennial mammography cost
      less than $50,000 per QALY gained for women aged 40 to 49 years with category 3
      or 4 breast density and either a previous breast biopsy or a family history of
      breast cancer. Annual mammography was not cost-effective for any group,
      regardless of age or breast density. RESULTS OF SENSITIVITY ANALYSIS: Mammography
      is expensive if the disutility of false-positive mammography results and the
      costs of detecting nonprogressive and nonlethal invasive cancer are considered.
      LIMITATION: Results are not applicable to carriers of BRCA1 or BRCA2 mutations.
      CONCLUSION: Mammography screening should be personalized on the basis of a
      woman's age, breast density, history of breast biopsy, family history of breast
      cancer, and beliefs about the potential benefit and harms of screening. PRIMARY
      FUNDING SOURCE: Eli Lilly, Da Costa Family Foundation for Research in Breast
      Cancer Prevention of the California Pacific Medical Center, and Breast Cancer
      Surveillance Consortium.

PMID- 21727290
TI  - Cardiovascular hospitalizations and mortality among recipients of hematopoietic
      stem cell transplantation.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is increasingly used
      to treat multiple malignant and nonmalignant conditions. The risk for
      cardiovascular disease after the procedure has not been well-described.
      OBJECTIVE: To compare rates and hazards of cardiovascular-related hospitalization
      and death among persons who were still alive at least 2 years after HSCT with
      those in a population-based sample. DESIGN: Retrospective cohort study. SETTING:
      Comprehensive cancer center. PATIENTS: 1491 patients who had survived 2 years or
      longer after HSCT received between 1985 and 2006, and frequency-matched persons
      who were randomly selected from drivers' license files in the state of
      Washington. MEASUREMENTS: Cardiovascular hospitalizations and death, as
      determined from statewide hospital discharge records and death registries in
      Washington. RESULTS: Compared with the general population, transplant recipients
      experienced increased cardiovascular death (adjusted incidence rate difference,
      3.6 per 1000 person-years [95% CI, 1.7 to 5.5]). Recipients also had an increased
      cumulative incidence of ischemic heart disease, cardiomyopathy or heart failure,
      stroke, vascular diseases, and rhythm disorders and an increased incidence of
      related conditions that predispose toward more serious cardiovascular disease
      (hypertension, renal disease, dyslipidemia, and diabetes). No consistent
      differences in hazards were observed after total-body irradiation or receipt of
      an allogeneic versus an autologous graft, aside from an increased rate of
      hypertension among recipients of allogeneic grafts. Disease relapse after
      transplantation was associated with an increased hazard of cardiovascular death
      (hazard ratio, 2.3 [CI, 1.1 to 4.8]). LIMITATION: All patients received HSCT at a
      single institution, and no information was available on pretransplantation
      treatment and lifestyle factors that may influence risk for cardiovascular
      disease. CONCLUSION: Increased rates of cardiovascular disease should be taken
      into account when caring for patients who have received HSCT. Future efforts
      should be directed toward improved screening and controlling of factors that
      predispose toward cardiovascular disease. PRIMARY FUNDING SOURCE: The American
      Society for Blood and Marrow Transplantation, the Leukemia and Lymphoma Society,
      and the Seattle Children's Research Institute.

PMID- 21727292
TI  - Single-center trials show larger treatment effects than multicenter trials:
      evidence from a meta-epidemiologic study.
AB  - BACKGROUND: A recent study suggested that results of single-center trials are
      frequently contradicted when similar trials are performed in multicenter
      settings. PURPOSE: To perform a meta-epidemiologic study to evaluate whether
      estimates of treatment effect differ between single-center and multicenter
      randomized, controlled trials (RCTs). DATA SOURCES: MEDLINE was searched via
      PubMed for meta-analyses of RCTs with binary outcomes that were published between
      August 2008 and January 2009 and in the first 6 months of 2010 in the 10 leading
      journals of each medical specialty. One issue of the Cochrane Database of
      Systematic Reviews was also searched. STUDY SELECTION: All individual RCTs
      included in the meta-analyses were selected. DATA EXTRACTION: Data were extracted
      and their quality was assessed by use of the risk of bias tool of the Cochrane
      Collaboration. DATA SYNTHESIS: The primary outcome was the ratio of odds ratios
      (ROR), used to quantify the difference in estimated intervention effect between
      single-center and multicenter RCTs. An ROR less than 1 would indicate larger
      estimates of the intervention effect in single-center trials. Sensitivity
      analyses were performed with adjustment for sample size, risk of bias within
      RCTs, and variance of the log odds ratio to take publication bias into account.
      Forty-eight meta-analyses were selected, including 421 RCTs (223 were single
      center and 198 were multicenter). Single-center RCTs showed a larger intervention
      effect than did multicenter RCTs (combined ROR, 0.73 [95% CI, 0.64 to 0.83]),
      with low heterogeneity across individual meta-analyses (I(2) = 12.0%; P = 0.24).
      Adjustment for sample size yielded consistent results (ROR, 0.85 [CI, 0.74 to
      0.97]), as did adjustment for risk of bias within RCTs, such as allocation
      concealment (ROR, 0.76 [CI, 0.67 to 0.86]), and variance of log odds ratio (ROR,
      0.83 [CI, 0.72 to 0.96]). LIMITATION: Despite sensitivity analyses, meta
      confounding cannot be fully excluded. CONCLUSION: Single-center RCTs showed
      larger treatment effects than did multicenter RCTs, a finding that was consistent
      in all sensitivity analyses. These results suggest that this item should be
      considered when the results of RCTs and meta-analyses are interpreted. PRIMARY
      FUNDING SOURCE: Academic grant Recherche sur la Recherche from the Delegation
      Interregionale a la Recherche Clinique (DIRC), Ile de France, Assistance Publique
      Hopitaux de Paris (APHP).

PMID- 21727291
TI  - Is pocket mobile echocardiography the next-generation stethoscope? A cross
      sectional comparison of rapidly acquired images with standard transthoracic
      echocardiography.
AB  - BACKGROUND: A pocket mobile echocardiography (PME) device is commercially
      available for clinical use, but public data documenting its accuracy compared
      with standard transthoracic echocardiography (TTE) are not available. OBJECTIVE:
      To compare the accuracy of rapidly acquired PME images with those acquired by
      standard TTE. DESIGN: Cross-sectional study. At the time of referral for TTE,
      ultrasonographers acquired PME images first in 5 minutes or less.
      Ultrasonographers were not blinded to the clinical indication for imaging or to
      the PME image results when obtaining standard TTE images. Two experienced
      echocardiographers and 2 cardiology fellows who were blinded to the indication
      for the study and TTE results but not to the device source interpreted the PME
      images. SETTING: Scripps Clinic Torrey Pines and Scripps Green Hospital, La
      Jolla, California. PATIENTS: Convenience sample of 97 patients consecutively
      referred for echocardiography. MEASUREMENTS: Visualizability and accuracy (the
      sum of proportions of true-positive and true-negative readings and observer
      variability) for ejection fraction, wall-motion abnormalities, left ventricular
      end-diastolic dimension, inferior vena cava size, aortic and mitral valve
      pathology, and pericardial effusion. RESULTS: Physician-readers could visualize
      some but not all echocardiographic measurements obtained with the PME device in
      every patient (highest proportions were for ejection fraction and left
      ventricular end-diastolic dimension [95% each]; the lowest proportion was for
      inferior vena cava size [75%]). Accuracy also varied by measurement (aortic valve
      was 96% [highest] and inferior vena cava size was 78% [lowest]) and decreased
      when nonvisualizability was accounted for (aortic valve was 91% and inferior vena
      cava size was 58%). Observer agreement was fair to moderate for some measurements
      among less-experienced readers. LIMITATION: The study was conducted at a single
      setting, there was no formal estimate of accuracy given the small convenience
      sample of patients, and few abnormal echocardiographic measurements occurred.
      CONCLUSION: The rapid acquisition of images by skilled ultrasonographers who use
      PME yields accurate assessments of ejection fraction and some but not all cardiac
      structures in many patients. Further testing of the device in larger patient
      cohorts with diverse cardiac abnormalities and with untrained clinicians
      obtaining and interpreting images is required before wide dissemination of its
      use can be recommended. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 21727293
TI  - Update in women's health: evidence published in 2010.

PMID- 21727294
TI  - To screen or not to screen women in their 40s for breast cancer: is personalized
      risk-based screening the answer?

PMID- 21727295
TI  - Metabias: a challenge for comparative effectiveness research.

PMID- 21727296
TI  - The lucky one.

PMID- 21727297
TI  - Autologous mesenchymal stem cells foster revascularization of ischemic limbs in
      systemic sclerosis.

PMID- 21727298
TI  - Actinomyces-induced inflammatory pseudotumor of the lymph node mimicking
      scrofula.

PMID- 21727299
TI  - Self-regulatory strength depletion and muscle-endurance performance: a test of
      the limited-strength model in older adults.
AB  - Self-regulation consumes a form of strength or energy. The authors investigated
      aftereffects of self-regulation depletion on muscle-endurance performance in
      older adults. Participants (N = 61, mean age = 71) were randomized to a self
      regulation-depletion or control group and completed 2 muscle-endurance
      performance tasks involving isometric handgrip squeezing that were separated by a
      cognitive-depletion task. The depletion group showed greater deterioration of
      muscle-endurance performance than controls, F(1, 59) = 7.31, p = .009. Results
      are comparable to those of younger adults in a similar study and support
      Baumeister et al.'s limited-strength model. Self-regulation may contribute to
      central-nervous-system fatigue; however, biological processes may allow aging
      muscle to offset depletion of self-regulatory resources affecting muscle
      endurance performance.

PMID- 21727300
TI  - Predicting habitual physical activity using coping strategies in older fallers
      engaged in falls-prevention exercise.
AB  - One third of adults over 65 yr old fall each year. Wide-ranging consequences
      include fracture, reduced activity, and death. Research synthesis suggests that
      falls-prevention programs can be effective in reducing falls by about 20%.
      Strength and balance training is the most efficacious component, and the assumed
      method of effect is an improvement in these performance domains. There is some
      evidence for this, but the authors have previously proposed an alternative
      method, activity restriction, leading to a reduction in subsequent falls through
      a reduction in exposure. The aim of this study was to examine physical activity
      in older fallers, applying a theory of adaptation, to ascertain predictors of
      habitual physical activity. Referrals to hospital- and community-based exercise
      programs were assessed for (a) habitual walking steps and (b) coping strategies,
      falls self-efficacy, social support, and balance mobility. There was no average
      group change in physical activity. There was high interindividual variability.
      Two coping strategies, loss-based selection and optimization, best explained the
      change in physical activity between baseline and follow-up. Notwithstanding some
      limitations, this work suggests further use of adaptation theory in falls
      research. A potential application is the creation of a profiling tool to enable
      clinicians to better match treatment to patient.

PMID- 21727301
TI  - Enhancing strength and postocclusive calf blood flow in older people with
      training with blood-flow restriction.
AB  - The response of calf-muscle strength, resting blood flow, and postocclusive blood
      flow (PObf) were investigated after 4 wk of low-load resistance training (LLRT)
      with and without blood-flow restriction in a matched-leg design. Ten untrained
      older individuals age 62-73 yr performed unilateral plantar-flexion LLRT at 25% 1
      repetition maximum (1RM). One limb was trained with normal blood flow and the
      other had blood flow restricted using a pressure cuff above the knee. 1RM,
      isometric maximal voluntary contraction, and isokinetic strength at 0.52 rad/s
      increased (p < .05) more after LLRT with blood-flow restriction than with normal
      blood flow. Peak PObf increased (p < .05) after LLRT with blood-flow restriction,
      compared with no change after LLRT with normal blood flow. These results suggest
      that 4 wk of LLRT with blood-flow restriction may be beneficial to older
      individuals to improve strength and blood-flow parameters.

PMID- 21727302
TI  - Validation of the OMNI-cycle scale of perceived exertion in the elderly.
AB  - This study examined the concurrent and construct validity of the OMNI-Cycle
      Rating of Perceived Exertion (RPE) Scale, using elderly men and women. Seventy
      six participants performed a load-incremented cycle-ergometer exercise test.
      Concurrent validity was determined by correlating OMNI-RPE responses with oxygen
      uptake, relative peak oxygen uptake, pulmonary ventilation, heart rate,
      respiratory rate, and respiratory-exchange ratio during a load-incremented cycle
      ergometer protocol. Construct validity was established by correlating RPE derived
      from the OMNI-Cycle Scale with RPE from the Borg (6-20) Scale. Multilevel, mixed
      linear-regression models indicated that OMNI-RPE distributed as a significant (p
      < .05) positive linear function (r = .81-.92) for all physiological measures.
      OMNI-RPE was positively (p < .01) and linearly related to Borg-RPE in elderly men
      (r = .97) and women (r = .96). This study demonstrates both concurrent and
      construct validity of the OMNI-Cycle RPE Scale. These findings support the use of
      this scaling metric with elderly men and women to estimate RPE during cycle
      ergometer exercise.

PMID- 21727303
TI  - Older patient-physician discussions about exercise.
AB  - This cross-sectional observational study examined the frequency of older patient
      physician discussions about exercise, who initiates discussions, and the quality
      of questioning, informing, and support about exercise. The study used a
      convenience sample of 396 follow-up visits at 3 community-based practice sites,
      with 376 community-dwelling older patients and 43 primary-care physicians.
      Audiotapes were analyzed using the Multi-Dimensional Interaction Analysis coding
      system. Results demonstrate that exercise was discussed in 13% of visits and the
      subject was raised equally by patients and physicians. Exercise was significantly
      more likely to be discussed in dyadic visits (14.7%) than in triadic visits
      (4.1%). Patient level of education, patient overall physical health, and the
      physician's being female were significant predictors of the occurrence of
      exercise discussion. Given the importance of exercise for maintaining health and
      independence in older adults, more clinical and research attention is needed to
      address barriers to effective discussions in this area.

PMID- 21727304
TI  - Item-response-theory analysis of two scales for self-efficacy for exercise
      behavior in people with arthritis.
AB  - Benefits of physical activity for those with arthritis are clear, yet physical
      activity is difficult to initiate and maintain. Self-efficacy is a key modifiable
      psychosocial determinant of physical activity. This study examined two scales for
      self-efficacy for exercise behavior (SEEB) to identify their strengths and
      weaknesses using item response theory (IRT) from community-based randomized
      controlled trials of physical activity programs in adults with arthritis. The 2
      SEEB scales included the 9-item scale by Resnick developed with older adults and
      the 5-item scale by Marcus developed with employed adults. All IRT analyses were
      conducted using the graded-response model. IRT assumptions were assessed using
      both exploratory and confirmatory factor analysis. The IRT analyses indicated
      that these scales are precise and reliable measures for identifying people with
      arthritis and low SEEB. The Resnick SEEB scale is slightly more precise at lower
      levels of self-efficacy in older adults with arthritis.

PMID- 21727305
TI  - Synergistic effect of social support and self-efficacy on physical exercise in
      older adults.
AB  - The purpose of the current study was to examine whether the effects of social
      support on physical exercise in older adults depend on individual perceptions of
      self-efficacy. Three hundred nine older German adults (age 65-85) were assessed
      at 3 points in time (3 months apart). In hierarchical-regression analyses,
      support received from friends and exercise self-efficacy were specified as
      predictors of exercise frequency while baseline exercise, sex, age, and physical
      functioning were controlled for. Besides main effects of self-efficacy and social
      support, an interaction between social support and self-efficacy emerged. People
      with low self-efficacy were less likely to be active in spite of having social
      support. People with low support were less likely to be active even if they were
      high in self-efficacy. This points to the importance of both social support and
      self-efficacy and implies that these resources could be targets of interventions
      to increase older adults' exercise.

PMID- 21727306
TI  - Strength-training behavior and perceived environment among Japanese older adults.
AB  - The authors examined the relationship between strength-training behavior and
      perceived environment in older Japanese adults. An Internet-based survey was
      conducted of 293 adults age 68.2 +/- 2.8 yr. The dependent variable was regular
      strength-training behavior. The IPAQ environment module, access to facilities for
      strength training, and home equipment for strength training were environmental
      factors. Logistic-regression analysis was employed. After demographic variables
      (gender, age, educational background, household income, body-mass index, self
      rated health status, smoking habit, and residential area) were adjusted for, home
      equipment for strength training (OR = 2.14, 95% CI = 1.50-3.06), access to
      facilities for strength training (OR = 2.53, 95% CI = 1.32-4.85), and observing
      active people (OR = 2.20, 95% CI = 1.06-4.58) were positively correlated with
      regular strength-training behavior. In conclusion, environmental factors
      associated with strength-training behavior were access to facilities for strength
      training, having home equipment for strength training, and observing active
      people.

PMID- 21727307
TI  - Uniaxial spin-transfer torque in an exchange-biased spin valve.
AB  - We study the effects of uniaxial spin-transfer torque (USTT) on the ferromagnetic
      (F) as well as antiferromagnetic (AF) layers in an exchange-biased (EB) spin
      valve. By analytically treating the free-energy functional of the F/AF bilayer
      and numerically solving the Landau-Lifshitz-Gilbert equation for magnetic
      moments, we can reproduce and explain two existing experimental facts relevant to
      USTT: one is that the EB field can be reversed by both positive and negative
      pulsed currents, and the other is that the critical current to excite the F
      moments is greatly increased in the presence of an AF layer and independent of
      external fields. We also derive the angular dependence of the critical currents
      to excite AF and F moments, which suggests a possible way to quantitatively
      determine USTT in experiments.

PMID- 21727308
TI  - Early-time particle dynamics and non-affine deformations during microstructure
      selection in solids.
AB  - Solid-solid transitions are invariably associated with groups of particles whose
      deformations cannot be expressed as an affine strain about a reference
      configuration. The dynamics of these non-affine zones (NAZ) determine the
      subsequent microstructure, i.e. the mesoscale patterning resulting from the
      structural transition. Here, we focus on early-time dynamics of individual
      particles within an NAZ associated with a nucleation event. We show that the
      early-time behavior of these particles have distinctive characteristics depending
      on the transition temperature. The dynamics is heterogeneous, consisting of a few
      active particles exhibiting complex intermittent jamming and flow in response to
      internal stresses generated during the transformation. At low temperatures, the
      dynamics of these active particles is ballistic and the structural transformation
      proceeds via string-like correlated movement of active particles, along ridges in
      the potential energy topography set up by inactive particles. On increasing
      temperature, the dynamics of active particles show an abrupt transition from
      ballistic to diffusive behavior with a diffusion coefficient which appears to be
      independent of temperature. This dynamical transition in the nature of the
      trajectories of particles is coincident with a discontinuous transition in the
      microstructure of the solid. Finally, we characterize this transition in terms of
      a dynamical order parameter in the space of trajectories and discuss its
      connection with the glass transition and rheology of soft and granular matter.

PMID- 21727309
TI  - Quantum criticality in organic conductors? Fermi liquid versus non-Fermi-liquid
      behaviour.
AB  - Organic metals exhibit unusual electronic properties in their charge and spin
      degrees of freedom that have puzzled physicists for decades. By now this
      behaviour is established as intrinsic and related to electronic interactions.
      Like other correlated electron systems, such as heavy fermions or transition
      metal oxides, organic conductors are located next to some ordered phase in the
      spin or charge sectors. Theory predicts quantum fluctuations to become important
      at low temperatures and quantum critical behaviour present in most physical
      properties. Here we survey the experimental evidence of quantum criticality in
      well-established organic model compounds and look for indications of non-Fermi
      liquid behaviour.

PMID- 21727310
TI  - First-principles study of stability of the bcc and omega phases of a low Al
      concentration Nb1-xAlx alloy.
AB  - The phase stability and site occupancy of bcc (body centered cubic) Nb(5)Al and
      slightly rearranged atomic structures have been examined by means of first
      principles calculations. In order to use first-principles methods, a periodic
      cell is required and we used ordered Nb(5)Al compounds as a tractable example of
      a low Al concentration Nb(1 - x)Al(x) alloy (in this case, for about 17 at.% Al).
      The instability against an omega-structure atomic displacement was also studied,
      since this structure is detrimental to ductility. Mulliken population analysis
      was used to provide an understanding of the hybridization between the atoms and
      the electronic origin of the site occupancy and instability of the underlying bcc
      structures. By making calculations for several different configurations of the Nb
      Al system we estimated the strengths of the Nb-Nb and Nb-Al bonds. It is shown
      that the stability of the underlying bcc phases is directly related to Nb-Nb and
      Nb-Al first-nearest-neighbor interactions. The first-principles calculations were
      extended to finite temperature by including various contributions to the free
      energy. In particular, the vibrational free energy was calculated within the
      quasiharmonic approximation, and it is shown that the contribution of the low
      energy modes to the lattice entropy helps to stabilize ordered bcc phases against
      omega-type phase transformations. Semi-quasi-random structures were employed to
      study the stability of the ordered and disordered bcc phases. Our study showed,
      in agreement with experiment, that the omega, ordered, and disordered phases can
      coexist in a nonequilibrium state at finite temperature.

PMID- 21727311
TI  - Magnetic and electronic properties of NpFeGa5.
AB  - NpFeGa(5) single crystals prepared by the Ga-flux method have been investigated
      by magnetisation, specific heat and (237)Np Mossbauer spectroscopy measurements.
      An antiferromagnetic (AF) transition has been observed at T(N) ~114 K. The second
      AF transition which takes place at T* ~74 K has only been detected in the
      magnetisation data. A saturated ordered Np moment of 1.00(5) MU(B) and the
      occurrence of an Np(3 + ) charge state were inferred from the Mossbauer data. The
      angle between the Np ordered moment and the basal plane was shown to be ~17
      degrees , in good agreement with the value observed by neutron diffraction in the
      low temperature AF phase. The absence of change of the quadrupole interaction
      parameters at T* did not allow us to gain information on the Np moment
      reorientation at T*. The trend of the isomer shift along the NpTGa(5) series and
      the discrepancy between the Np moments determined by neutron diffraction and
      Mossbauer spectroscopy indicated a partial spatial delocalisation of the 5f
      electrons in NpFeGa(5).

PMID- 21727312
TI  - Fabrication of three-dimensional scaffolds using precision extrusion deposition
      with an assisted cooling device.
AB  - In the field of biofabrication, tissue engineering and regenerative medicine,
      there are many methodologies to fabricate a building block (scaffold) which is
      unique to the target tissue or organ that facilitates cell growth, attachment,
      proliferation and/or differentiation. Currently, there are many techniques that
      fabricate three-dimensional scaffolds; however, there are advantages, limitations
      and specific tissue focuses of each fabrication technique. The focus of this
      initiative is to utilize an existing technique and expand the library of
      biomaterials which can be utilized to fabricate three-dimensional scaffolds
      rather than focusing on a new fabrication technique. An expanded library of
      biomaterials will enable the precision extrusion deposition (PED) device to
      construct three-dimensional scaffolds with enhanced biological, chemical and
      mechanical cues that will benefit tissue generation. Computer-aided motion and
      extrusion drive the PED to precisely fabricate micro-scaled scaffolds with
      biologically inspired, porosity, interconnectivity and internal and external
      architectures. The high printing resolution, precision and controllability of the
      PED allow for closer mimicry of tissues and organs. The PED expands its library
      of biopolymers by introducing an assisting cooling (AC) device which increases
      the working extrusion temperature from 120 to 250  degrees C. This paper
      investigates the PED with the integrated AC's capabilities to fabricate three
      dimensional scaffolds that support cell growth, attachment and proliferation.
      Studies carried out in this paper utilized a biopolymer whose melting point is
      established to be 200  degrees C. This polymer was selected to illustrate the
      newly developed device's ability to fabricate three-dimensional scaffolds from a
      new library of biopolymers. Three-dimensional scaffolds fabricated with the
      integrated AC device should illustrate structural integrity and ability to
      support cell attachment and proliferation.

PMID- 21727313
TI  - pH-sensitive photoluminescence for aqueous thiol-capped CdTe nanocrystals.
AB  - pH-sensitive photoluminescence (PL) is an important property of aqueous
      nanocrystals (NCs) towards NCs-based intelligent applications. Previous works
      mainly focused on the effect of pH during NC growth process on PL of the aqueous
      NCs. The effect of pH during application process on PL of as-prepared NCs is
      still not fully understood. In this work, we brought out a general mechanism for
      the pH-sensitive PL behaviors of as-prepared aqueous CdTe NCs capped by aqueous
      thiol ligands, such as carboxylic-acid-terminated 3-mercaptopropionic acid (MPA)
      and thioglycolic acid (TGA) ligands, hydroxyl-terminated 1-thioglycerol (TG)
      ligands and amine-terminated 2-mercaptoethylamine (MA) ligands. A major
      contribution of this work is finding the key role of ligand terminal groups in
      the diffuse process of free Cd-ligand complexes toward NCs. This terminal group
      effect is the main reason for PL alteration of NCs during pH adjustment process.
      Besides the terminal group effect, PL of aqueous NCs is also affected by the
      aggregation effect, the thiol group effect and the counter ion effect. These
      effects make different contributions to PL of NCs at different pH ranges. By
      using this mechanism, we successfully explained the complex pH-sensitive PL
      behaviors of MPA, TGA, TG and MA-capped CdTe NCs.

PMID- 21727314
TI  - Electrochemical growth of high-aspect ratio nanostructured silver chloride on
      silver and its application to miniaturized reference electrodes.
AB  - The sensitivity of many biological and chemical sensors is critically dependent
      on the stability of the potential of the reference electrode being used. The
      stability of a reference electrode's potential is highly influenced by the
      properties of its surface. In this paper, for the first time, the formation of
      nanosheets of silver chloride on silver wire is observed and controlled using
      high anodic constant potential (>0.5 V) and pulsed electrodeposition. The
      resulting nanostructured morphology substantially improves the electrode's
      potential stability in comparison with the conventional globular surface
      structure. The increased stability is attributed to the increase in the surface
      area of the silver chloride produced by the nanosheet formation.

PMID- 21727315
TI  - Increasing the efficiency of polymer solar cells by silicon nanowires.
AB  - Silicon nanowires have been introduced into P3HT:[60]PCBM solar cells, resulting
      in hybrid organic/inorganic solar cells. A cell efficiency of 4.2% has been
      achieved, which is a relative improvement of 10% compared to a reference cell
      produced without nanowires. This increase in cell performance is possibly due to
      an enhancement of the electron transport properties imposed by the silicon
      nanowires. In this paper, we present a novel approach for introducing the
      nanowires by mixing them into the polymer blend and subsequently coating the
      polymer/nanowire blend onto a substrate. This new onset may represent a viable
      pathway to producing nanowire-enhanced polymer solar cells in a reel to reel
      process.

PMID- 21727316
TI  - Tunning pore filling of anodic alumina templates by accurate control of the
      bottom barrier layer thickness.
AB  - The role of the alumina barrier layer thickness (delta(b)) on the growth of Ni
      nanowires (NWs) in porous anodic alumina (PAA) has been revealed. By varying the
      final anodization voltage to form dendrites at the bottom of the nanoporous
      structure, we are able to optimize delta(b) (in the 2-16 nm range), allowing us
      to obtain a Ni pore filling percentage (f(p)) of almost 100% for delta(b) = 10
      nm. However, deviations from this optimal delta(b)-value led to a strong decrease
      of f(p). Moreover, an increase of the electrodeposition efficiency (EE) and NW
      homogeneity was also verified for delta(b) up to 10 nm. Such increase in nominal
      delta(b) leads to a consistent growth rate in all pores and consequently a
      complete and uniform nanopore filling. On the other hand, the decrease in
      electrodeposition efficiency visible for delta(b) > 10 nm is related with
      hydrogen evolution and dielectric breakdown of the insulator layer due to the
      required high deposition voltages. Non-uniform NW growth is then visible, with
      the consequent decrease in f(p). The control of the pore filling and length
      homogeneity of the fabricated 1D metallic nanostructures, combined with the
      ability to adjust the pore dimensions of PAA, can bring novel approaches for the
      fabrication of nano-objects and thus exciting new applications.

PMID- 21727317
TI  - Wettability changes of TiO2 nanotube surfaces.
AB  - This study examines the effect of environmental and experimental conditions, such
      as temperature and time, on the wettability properties of titania nanotube (TNT)
      surfaces fabricated by anodization. The fabricated TNTs are 60-130 nm inner
      diameter and 7-10 um height. One-microliter water droplets were used to define
      the wettability of the TNT surfaces by measuring the contact angles. A digital
      image analysis algorithm was developed to obtain contact angles, contact radii
      and center heights of the droplets on the TNT surfaces. Bare titanium foil is
      inherently less hydrophilic with approximately 60 degrees -80 degrees  contact
      angle. The as-anodized TNT surfaces are more hydrophilic and annealing further
      increases this hydrophilic property. Furthermore, it was found that the TNT
      surface became more hydrophobic when aged in air over a period of three months.
      It is believed that the surface wettability can be changed due to alkane
      contamination and organic contaminants in an ambient atmosphere. This work can
      provide guidelines to better specify the environmental conditions that changes
      surface properties of TNT surfaces and therefore affect their desirable function
      in specific applications such as orthopedic implants.

PMID- 21727318
TI  - Indirect identification and compensation of lateral scanner resonances in atomic
      force microscopes.
AB  - Improving the imaging speed of atomic force microscopy (AFM) requires accurate
      nanopositioning at high speeds. However, high speed operation excites resonances
      in the AFM's mechanical scanner that can distort the image, and therefore typical
      users of commercial AFMs elect to operate microscopes at speeds below which
      scanner resonances are observed. Although traditional robust feedforward
      controllers and input shaping have proven effective at minimizing the influence
      of scanner distortions, the lack of direct measurement and use of model-based
      controllers have required disassembling the microscope to access lateral scanner
      motion with external sensors in order to perform a full system identification
      experiment, which places excessive demands on routine microscope operators.
      Further, since the lightly damped instrument dynamics often change from
      experiment to experiment, model-based controllers designed from offline system
      identification experiments must trade off high speed performance for robustness
      to modeling errors. This work represents a new way to automatically characterize
      the lateral scanner dynamics without addition of lateral sensors, and shape the
      commanded input signals in such a way that disturbing dynamics are not excited.
      Scanner coupling between the lateral and out-of-plane directions is exploited and
      used to build a minimal model of the scanner that is also sufficient to describe
      the nature of the distorting resonances. This model informs the design of an
      online input shaper used to suppress spectral components of the high speed
      command signals. The method presented is distinct from alternative approaches in
      that neither an information-complete system identification experiment nor
      microscope modification are required. Because the system identification is
      performed online immediately before imaging, no tradeoff of performance is
      required. This approach has enabled an increase in the scan rates of unmodified
      commercial AFMs from 1-4 lines s(-1) to over 40 lines s(-1).

PMID- 21727319
TI  - Thermal boundary resistance between the end of an individual carbon nanotube and
      a Au surface.
AB  - The thermal boundary resistance between an individual carbon nanotube and a Au
      surface was measured using a microfabricated hot-film sensor. We used both closed
      and open-ended multi-walled carbon nanotubes and obtained thermal boundary
      resistance values of 0.947-1.22 * 10(7) K W(-1) and 1.43-1.76 * 10(7) K W(-1),
      respectively. Considering all uncertainties, including the contact area, the
      thermal boundary conductances per unit area were calculated to be 8.6 * 10(7)-2.2
      * 10(8) W m(-2) K(-1) for c-axis orientation and 4.2 * 10(8)-1.2 * 10(9) W m(-2)
      K(-1) for the a-axis. The trend in these values agrees with the predicted
      conductance dependence on the interface orientation of anisotropic carbon-based
      materials. However, the measured thermal boundary conductances are found to be
      much larger than the reported results.

PMID- 21727320
TI  - Characterization of functionalized nanoporous supports for protein confinement.
AB  - Here we characterize a highly efficient approach for protein confinement and
      enzyme immobilization in NH(2)- or HOOC- functionalized mesoporous silica (FMS)
      with pore sizes as large as tens of nanometres. We observed a dramatic increase
      of enzyme loading in both enzyme activity and protein amount when using
      appropriate FMS in comparison with unfunctionalized mesoporous silica and normal
      porous silica. With different protein loading density in NH(2)-FMS, the
      negatively charged glucose oxidase (GOX) displayed an immobilization efficiency
      (I(e), the ratio of the specific activity of the immobilized enzyme to the
      specific activity of the free enzyme in stock solution) in a range from 30% to
      160%, while the same charged glucose isomerase (GI) showed an I(e) of 100% to
      120%, and the positively charged organophosphorus hydrolase (OPH) exhibited I(e)
      of more than 200% in HOOC-FMS. The enzyme-FMS composite was stained with the
      charged gold nanoparticles and imaged by transmission electron microscopy (TEM).
      Fourier transform infrared (FTIR) spectroscopy showed no major secondary
      structural change for the enzymes entrapped in FMS. Thanks to the large, rigid,
      open pore structure of FMS, the reaction rate and K(m) of the entrapped enzymes
      in FMS were comparable to those of the free enzymes in solution. In principle,
      the general approach described here should be applicable to many enzymes,
      proteins, and protein complexes since both pore sizes and functional groups of
      FMS are controllable.

PMID- 21727321
TI  - Fabrication of Fe(3)O(4) nanoparticle arrays via patterned template assisted self
      assembly.
AB  - Magnetic nanoparticle arrays have been fabricated by combining chemically
      synthesized Fe(3)O(4) nanoparticles with a diblock copolymer template substrate
      consisting of self-assembled polystyrene (PS) dots in a polymethylmethacrylate
      (PMMA) matrix. The influence of the volume fraction of the Fe(3)O(4) suspending
      solution and the withdrawal speed of the template on the formation of array
      structures was investigated. A small volume fraction of the nanoparticles and low
      withdrawal speed play an important role in the fabrication of the patterned
      arrays of nanoparticles via template assisted self-assembly. Below a withdrawal
      speed of 0.5 mm s(-1) and a nanoparticle volume fraction below 0.05 vol% (in
      particular, at extremely high dilutions of less than 0.01 vol%), the selective
      deposition of one to several nanoparticles on every single PS dot becomes
      possible.

PMID- 21727322
TI  - Chemical vapour deposition of oriented diamond nanocrystallites by a bias
      enhanced nucleation method.
AB  - A microwave plasma chemical vapour deposition (MPCVD) system has been used to
      deposit nanometre-sized single-crystalline diamonds on 1 * 1 cm(2) Si(100)
      substrates. The distribution of deposited diamonds has good uniformity over the
      whole Si substrate surface by using a dome-shaped Mo anode which allows the
      application of bias-enhanced nucleation. The morphology and crystallinity of the
      deposits on Si were characterized by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) with electron diffraction and lattice
      images. SEM and TEM observations show that oriented diamond nuclei as single
      crystals with facets can form on self-formed Si cones through epitaxial SiC
      within a short bias period. After a longer bias time, it has been observed that
      polycrystalline diamonds formed as a result of secondary nucleation.

PMID- 21727323
TI  - Growth mechanisms of one-dimensional zinc oxide hierarchical structures.
AB  - One-dimensional (1D) zinc oxide (ZnO) hierarchical structures have been self
      assembled on amorphous carbons using thermal chemical vapour transport and
      condensation. Three typical micro- and nanostructures consisting of micrometre
      sized rods and nanometre-sized needles were observed. Growth mechanisms were
      established to elucidate the growth properties of 1D ZnO hierarchical structures.

PMID- 21727324
TI  - Wurtzite ZnSe nanowires: growth, photoluminescence, and single-wire Raman
      properties.
AB  - Wurtzite ZnSe nanowires were prepared on GaAs substrates in a metal-organic
      chemical vapour deposition system. Electron microscopy shows that they are smooth
      and uniform in size. Both transmission electron microscopy and x-ray diffraction
      reveal the wurtzite structure of the nanowires, which grows along the [Formula:
      see text] direction. Raman scattering studies on individual nanowires were
      performed in the back-scattering geometry at room temperature. Besides the
      commonly observed longitudinal and transverse optical phonon modes, a possible
      surface mode located at 233 cm(-1) is also observed in the Raman spectrum. A peak
      located at 2.841 eV was clearly observed in the photoluminescence spectra of the
      nanowires, which can be assigned to near band edge emissions of wurtzite ZnSe.

PMID- 21727325
TI  - Optically transparent magnetic nanocomposites based on encapsulated Fe(3)O(4)
      nanoparticles in a sol-gel silica network.
AB  - Composite Fe(3)O(4)-SiO(2) materials were prepared by the sol-gel method with
      tetraethoxysilane and aqueous-based Fe(3)O(4) ferrofluids as precursors. The
      monoliths obtained were crack free and showed both optical and magnetic
      properties. The structural properties were determined by infrared spectroscopy, x
      ray diffractometry and transmission electron microscopy. Fe(3)O(4) particles of
      20 nm size lie within the pores of the matrix without any strong Si-O-Fe bonding.
      The well established silica network provides effective confinement to these
      nanoparticles. The composites were transparent in the 600-800 nm regime and the
      field dependent magnetization curves suggest that the composite exhibits
      superparamagnetic characteristics.

PMID- 21727326
TI  - Fabrication and field emission property of a Si nanotip array.
AB  - Using a Si-based porous anodic alumina membrane as a mask, we demonstrate a way
      to pattern Si surface. After removing the SiO(2) nanoislands formed during
      anodization of the Al/Si interface, we obtain a Si nanotip array on the surface
      of a Si wafer. This array shows an excellent field emission property with a low
      turn-on field of 8.5 V um(-1). The Fowler-Nordheim plot obtained is linearly
      dependent, indicating that the emission current arises from the quantum
      tunnelling effect. The Si nanotip array can be expected to have important
      applications in nanoelectronic devices.

PMID- 21727327
TI  - Fabrication and electrical characterization of circuits based on individual tin
      oxide nanowires.
AB  - Two- and four-probe electrical measurements on individual tin oxide (SnO(2))
      nanowires were performed to evaluate their conductivity and contact resistance.
      Electrical contacts between the nanowires and the microelectrodes were achieved
      with the help of an electron- and ion-beam-assisted direct-write nanolithography
      process. High contact resistance values and the nonlinear current-bias (I-V)
      characteristics of some of these devices observed in two-probe measurements can
      be explained by the existence of back-to-back Schottky barriers arising from the
      platinum-nanowire contacts. The nanoscale devices described herein were
      characterized using impedance spectroscopy, enabling the development of an
      equivalent circuit. The proposed methodology of nanocontacting and measurements
      can be easily applied to other nanowires and nanometre-sized materials.

PMID- 21727328
TI  - Preparation and characterization of rare-earth bulks with controllable
      nanostructures.
AB  - The preparation and characterization of pure rare-earth-metal bulks with
      controllable nanostructures are reported in this paper. A novel 'oxygen-free' in
      situ synthesis technique that combines inert-gas condensation with spark plasma
      sintering (SPS) technology is proposed. Taking into account the special
      mechanisms of SPS consolidation and the scale effects of nanoparticles, we
      introduced practical procedures for preparing rare-earth bulks of amorphous,
      mixed amorphous and nanocrystals, and nanocrystalline microstructures,
      respectively. Compared with the conventional polycrystalline bulk, these
      nanostructured bulks exhibit substantially improved physical and mechanical
      properties. This technique enables comprehensive studies on the microstructures
      and properties of a large variety of nanostructured metallic materials that are
      highly reactive in the air.

PMID- 21727329
TI  - An approach for synthesizing various types of tungsten oxide nanostructure.
AB  - Various types of tungsten oxide nanostructures, including nanowires, nanobundles,
      and three-dimensional nanowire networks, have been synthesized on large-area
      silicon substrates by simply heating an array of tungsten filaments in a vacuum
      chamber. The fine structure and components of as-prepared products can been
      controlled by changing the tungsten filament temperature. This approach is free
      of catalysts and templates, and provides an economical method for large-scale
      preparation of various types of tungsten oxide nanostructures for applications.

PMID- 21727330
TI  - Deposition of metallic nanoparticles on carbon nanotubes via a fast evaporation
      process.
AB  - A new technique was developed for the deposition of colloidal metal nanoparticles
      on carbon nanotubes. It involves fast evaporation of a suspension containing
      sonochemically functionalized carbon nanotubes and colloidal nanoparticles. It
      was demonstrated that metallic nanoparticles with different sizes and
      concentrations can be deposited on the carbon nanotubes with only a few
      agglomerates. The technique does not seem to be limited by what the nanoparticles
      are, and therefore would be applicable to the deposition of other nanoparticles
      on carbon nanotubes. PtPd and CoPt(3) alloy nanoparticles were used to
      demonstrate the deposition process. It was found that the surfactants used to
      disperse the nanoparticles can hinder the nanoparticle deposition. When the
      nanoparticles were washed with ethanol, they could be well deposited on the
      carbon nanotubes. The obtained carbon nanotube supported metal nanoparticles were
      characterized by transmission electron microscopy, energy dispersive x-ray
      spectroscopy, x-ray photoelectron spectroscopy, and cyclic voltammetry.

PMID- 21727331
TI  - Modification of multi-walled carbon nanotubes by plasma treatment and further use
      as templates for growth of CdS nanocrystals.
AB  - In this study, we present a novel method for preparing multi-walled carbon
      nanotubes (MWCNTs) grafted with a poly(2-methacrylic acid 3-(bis
      carboxymethylamino)-2-hydroxy-propyl ester) (GMA-IDA)-cadmium sulfide complex
      (CNTs-G-ICdS complex) through plasma-induced grafting polymerization. The
      characteristics of the MWCNTs after being grafted with the GMA-IDA polymer were
      monitored by a Fourier transform infrared (FT-IR) spectroscope. Scanning
      electronic microscopy (SEM) shows that the amount of GMA-IDA grafted onto the
      MWCNTs increases with the concentration of GMA-IDA monomer. The complex resulting
      from GMA-IDA polymer grafting onto the MWCNTs, CNTs-G-I (15%), shows excellent
      dispersion properties in aqueous solution and has high Zeta potential values over
      a wide range of pH values, from 2 to 12. Moreover, Raman spectroscopy was used to
      confirm the successful chemical modification of MWCNTs through the plasma
      treatment. The chelating groups, -N(CH(2)COO(-))(2) in the GMA-IDA polymer
      grafted on the surface of the CNTs-G-I, are the coordination sites for chelating
      cadmium ions, and are further used as nano-templates for the growth of CdS
      nanocrystals (quantum dots). Moreover, TEM microscopy reveals that the size of
      the CdS nanocrystals on the CNT surfaces increases with increasing S(2-)
      concentration. In addition, high resolution x-ray photoelectron (XPS)
      spectroscopy was used to characterize the functional groups on the surface of the
      MWCNTs after chemical modification by the plasma treatment and grafting with GMA
      IDA polymer.

PMID- 21727332
TI  - Solution-phase synthesis of germanium nanoclusters using sulfur.
AB  - Sulfur is used to promote the formation of germanium nanocrystals from the robust
      organometallic precursor, triphenylgermanium chloride, at elevated temperatures
      (300  degrees C) in the surfactant/solvent hexadecylamine. Transmission electron
      microscopy shows that 8 nm germanium nanocrystals are produced that self-assemble
      into uniform-sized 60 nm germanium nanoclusters after purification. Electron
      diffraction studies show that the germanium nanoclusters have a diamond germanium
      crystal structure and energy dispersive x-ray spectroscopy shows that the
      nanoclusters are primarily composed of pure germanium.

PMID- 21727333
TI  - Mechanical properties of amorphous nanosprings.
AB  - Helical amorphous nanosprings have attracted particular interest due to their
      special mechanical properties. In this work we present a simple model, within the
      framework of the Kirchhoff rod model, for investigating the structural properties
      of nanosprings having asymmetric cross section. We have derived expressions that
      can be used to obtain the Young's modulus and Poisson's ratio of the nanospring
      material composite. We also address the importance of the presence of a catalyst
      in the growth process of amorphous nanosprings in terms of the stability of
      helical rods.

PMID- 21727334
TI  - Comparative analysis of cavity length-dependent temperature sensitivity of
      GaInNAs quantum dot lasers and quantum well lasers.
AB  - Self-assembled GaInNAs/GaAsN single-layer quantum dot (QD) lasers, grown using
      solid source molecular beam epitaxy, have been fabricated and characterized. A
      high output power of 40.76 mW/facet was obtained from a GaInNAs QD laser with
      dimensions of 50 * 700 um(2) at 10  degrees C. Temperature-dependent measurements
      were carried out on the GaInNAs QD lasers of different cavity lengths. For
      comparison, temperature-dependent measurements were also performed on GaInNAs
      single quantum well (SQW) and triple QW (TQW) lasers. Unlike the relationship
      between cavity length and T(0) in GaInNAs SQW/TQW lasers, longer-cavity GaInNAs
      QD lasers (50 * 1700 um(2)) showed a lower T(0) of 65.1 K, which is believed to
      be due to non-uniformity of the GaInNAs QD layer. Furthermore, compared to
      GaInNAs SQW lasers, a significant improvement in temperature sensitivity was
      observed in the TQW GaInNAs lasers. This is attributed to a reduction in the
      relative contribution of the Auger recombination current and suppression of heavy
      hole leakage in the TQW laser structures.

PMID- 21727335
TI  - Conductance of carbon nanotubes in a transverse electric field and an arbitrary
      magnetic field.
AB  - The electronic and transport properties of carbon nanotubes subject to the
      influences of a transverse electric field and an arbitrary magnetic field are
      studied by the tight-binding model. The external fields would modify the energy
      dispersions, destroy the state degeneracy, change the symmetry characteristics,
      alter the energy gap, modulate the electron effective mass, and create extra band
      edge states. The energy gap and the electron effective mass exhibit a rich
      dependence on the field strength, the magnetic field direction, and the types of
      carbon nanotubes. A semiconductor-metal transition would be allowed for certain
      field strengths and magnetic field directions. The variations of energy
      dispersions with the external fields will also be reflected in the conductance.
      Special features of the conductance, such as single-shoulder, multi-shoulder, and
      spike structures, are predicted.

PMID- 21727336
TI  - Morphological transition of gold nanostructures induced by continuous ultraviolet
      irradiation.
AB  - Gold nanoparticles were synthesized through a continuous UV irradiation method
      using citric acid as a reducer and protective agent. After a period of continuous
      UV irradiation, the nanoparticles transformed into two-dimensional (2D)
      nanonetworks, porous nanoplates and compact nanoplates with hexagonal, triangular
      or truncated triangular pores through a self-assembly process which was dependent
      on the citric acid concentration. Selected area electron diffraction (SAED)
      patterns indicated that both the nanonetworks and the porous nanoplates were
      single crystalline. The influence of citric acid concentration and irradiation
      time on the morphological transition of Au nanostructures was investigated. The
      process of morphological transition was presumably discussed.

PMID- 21727337
TI  - Direct synthesis of single-walled carbon nanotubes selectively suspended on tips
      of vertically aligned silicon nanostructures fabricated by hydrogen plasma
      etching.
AB  - Here we present a method to synthesize single-walled carbon nanotubes (SWNTs)
      selectively suspended on tips of silicon-based nanostructure (Si-ns) templates.
      The Si-ns templates vertically aligned to the substrates are fabricated via an
      anisotropic etch process using reactive hydrogen plasmas, in which the etch
      resistive nanomasks are the nanosized particles formed by thermal annealing of
      multi-layered catalytic thin films. After plasma etching, the nanosized self
      masks remaining at the tips of the Si-ns directly serve as the catalysts for SWNT
      growth by thermal chemical vapour deposition. Consequently, the synthesized SWNTs
      are selectively suspended on the tips of the Si-ns, as revealed by
      characterizations using scanning electron microscopy and resonance Raman
      spectroscopy. This methodology provides a simple and straightforward approach to
      assemble two different nanomaterials, i.e., Si-ns and suspended SWNTs, together
      as a building block for constructing nanodevices for possible applications.

PMID- 21727338
TI  - Determination of the strain generated in InAs/InP quantum wires: prediction of
      nucleation sites.
AB  - The compositional distribution in a self-assembled InAs(P) quantum wire grown by
      molecular beam epitaxy on an InP(001) substrate has been determined by electron
      energy loss spectrum imaging. We have determined the strain and stress fields
      generated in and around this wire capped with a 5 nm InP layer by finite element
      calculations using as input the compositional map experimentally obtained.
      Preferential sites for nucleation of wires grown on the surface of this InP
      capping layer are predicted, based on chemical potential minimization, from the
      determined strain and stress fields on this surface. The determined preferential
      sites for wire nucleation agree with their experimentally measured locations. The
      method used in this paper, which combines electron energy loss spectroscopy, high
      resolution Z contrast imaging, and elastic theory finite element calculations, is
      believed to be a valuable technique of wide applicability for predicting the
      preferential nucleation sites of epitaxial self-assembled nano-objects.

PMID- 21727339
TI  - Molecular transport in a crowded volume created from vertically aligned carbon
      nanofibres: a fluorescence recovery after photobleaching study.
AB  - Rapid and selective molecular exchange across a barrier is essential for
      emulating the properties of biological membranes. Vertically-aligned carbon
      nanofibre (VACNF) forests have shown great promise as membrane mimics, owing to
      their mechanical stability, their ease of integration with microfabrication
      technologies and the ability to tailor their morphology and surface properties.
      However, quantifying transport through synthetic membranes having micro- and
      nanoscale features is challenging. Here, fluorescence recovery after
      photobleaching (FRAP) is coupled with finite difference and Monte Carlo
      simulations to quantify diffusive transport in microfluidic structures containing
      VACNF forests. Anomalous subdiffusion was observed for FITC (hydrodynamic radius
      of 0.54 nm) diffusion through both VACNFs and SiO(2)-coated VACNFS (oxVACNFs).
      Anomalous subdiffusion can be attributed to multiple FITC-nanofibre interactions
      for the case of diffusion through the VACNF forest. Volume crowding was
      identified as the cause of anomalous subdiffusion in the oxVACNF forest. In both
      cases the diffusion mode changes to a time-independent, Fickian mode of transport
      that can be defined by a crossover length (R(CR)). By identifying the space-and
      time-dependent transport characteristics of the VACNF forest, the dimensional
      features of membranes can be tailored to achieve predictable molecular exchange.

PMID- 21727340
TI  - Resistance switch employing a simple metal nanogap junction.
AB  - In recent years, several researchers have reported the occurrence of reversible
      resistance switching effects in simple metal nanogap junctions. A large negative
      resistance is observed in the I-V characteristics of such a junction when high
      bias voltages are applied. This phenomenon is characteristic behaviour on the
      nanometre scale; it only occurs for gap widths slightly under 13 nm. Furthermore,
      such a junction exhibits a non-volatile resistance hysteresis when the bias
      voltage is reduced very rapidly from a high level to around 0 V, and when the
      bias voltage is reduced slowly. This non-volatile resistance change occurs as a
      result of changes in the gap width between the metal electrodes, brought about by
      the applied bias voltage.

PMID- 21727341
TI  - Radiation hardness of the electrical properties of carbon nanotube network field
      effect transistors under high-energy proton irradiation.
AB  - The effect of high-energy proton irradiation on the physical properties of carbon
      nanotubes (CNTs) was investigated. The focus of the study was on the electrical
      properties of single-walled carbon nanotube (SWNT) network devices exposed to
      proton beams. Field-effect transistors (FETs) of network type were fabricated
      using SWNTs and were then irradiated by high-energy proton beams of 10-35 MeV
      with a fluence of 4 * 10(10)-4 * 10(12) cm(-2) that are comparable to the
      aerospace radiation environment. The electrical properties of both metallic and
      semiconducting CNT network FET devices underwent no significant change after the
      high-energy proton irradiation, indicating that the CNT network devices are very
      tolerant in proton beams. Raman spectra confirm the proton-radiation hardness of
      CNT network FET devices. The radiation hardness of CNT network FET devices
      promises therefore the potential usefulness of CNT-based electronics for future
      space application.

PMID- 21727342
TI  - 'One-step' controllable synthesis of Ag and Ag(2)S nanocrystals on a large scale.
AB  - Ag and Ag(2)S nanocrystals (NCs) were synthesized by a simple 'one-step' process.
      Dodecanethiol played three important roles in the synthesis: as the capping
      reagent, reducer (for the synthesis of Ag) and S(2-) source (for the synthesis of
      Ag(2)S). Due to the multifunctional characteristic of dodecanethiol, only two
      reactants (silver nitrate and dodecanethiol) are needed in the synthesis,
      avoiding the use of toxic organic solvents and a complex reaction procedure. X
      ray powder diffraction and transmission electron microscopy studies indicated
      that both the phase (Ag or Ag(2)S) and the particle size were controlled by
      reaction parameters. The infrared spectra studies indicated that the
      nanoparticles were stabilized by dodecanethiol. As a result, the particles were
      stable (no irreversible conglomeration) in the solid state and in solution for
      several months. In addition, a large quantity of Ag and Ag(2)S NCs could be
      readily obtained. A possible formation and size evolution mechanism for Ag and
      Ag(2)S NCs was proposed.

PMID- 21727343
TI  - Simple template-free solution route for the synthesis of Ni(SO(4))(0.3)(OH)(1.4)
      nanobelts and their thermal degradation.
AB  - Nanobelts of nickel hydroxyl sulfate have been prepared on a large scale via a
      simple template-free hydrothermal reaction on the basis of a complex
      [Ni(NH(3))(6)](2+) formed with Ni(2+) and ammonia in an ethanol-water solution.
      The as-synthesized nanobelts were single crystals, with several tens of microns
      in length and 50-150 nm in width. The nanobelts were enclosed by top surfaces
      (100) and side surfaces (001) and their growth direction was parallel to [010].
      The function of aqueous ammonia and ethanol was discussed. Furthermore,
      nanostructures of a mixture of crystralline NiO and amorphous nickel sulfate with
      various morphologies, such as nanobelts, porous nanobelts, and nanoparticles,
      were obtained by the thermal treatment of the as-synthesized
      Ni(SO(4))(0.3)(OH)(1.4) nanobelts at different temperatures.

PMID- 21727344
TI  - Large-scale submicron horizontally aligned single-walled carbon nanotube surface
      arrays on various substrates produced by a fluidic assembly method.
AB  - Single-walled carbon nanotube (CNT) arrays have been assembled on various
      substrates over mm-scale surface areas by combining fluidic alignment with soft
      lithography (micropatterning in capillaries) techniques. The feature size of the
      nanotube patterns reaches down to submicrometre scale. To this end, tailored
      substrate surface modification and pre-alignment of chopped CNTs in suspension
      are highly critical.

PMID- 21727345
TI  - The large-scale synthesis and characterization of carbon nanotubes filled with
      long continuous inorganic nanowires in supercritical CS(2).
AB  - Large-scale long continuous FeS(2) nanowire filled carbon nanotubes (CNTs) were
      one-step synthesized in the presence of NaN(3) in supercritical CS(2) at 500 
      degrees C using ferrocene as the iron source. The CNTs have outer diameters in
      the range of 15-25 nm and the core FeS(2) nanowires inside CNTs are characterized
      as single crystals, with an average diameter of 8 nm and up to several
      micrometres in length. The band gap of FeS(2) nanowire filled CNTs was determined
      as 5.69 eV from the ultraviolet and visible light absorption spectrum, showing
      its promise for application in reversible conversion between solar energy and
      electrical or chemical energy.

PMID- 21727346
TI  - Modelling the formation of high aspect CdSe quantum wires: axial-growth versus
      oriented-attachment mechanisms.
AB  - Following the recent low temperature synthesis of high quality and single crystal
      CdSe quantum nanowires, we have used a thermodynamic model to investigate the
      plausibility of axial-growth and oriented-attachment formation mechanisms. Using
      surface energies for clean and alkylamine-passivated CdSe surfaces reported
      elsewhere by Manna et al (2005 J. Phys. Chem. B 109 6183), we have compared
      equilibrium and metastable shapes of CdSe nanowires as a function of aspect ratio
      and axial orientation for different degrees of surface passivation. In general,
      the theoretical results support the oriented-attachment of low aspect quantum
      dots or nanorods, followed by coalescence to form high aspect [Formula: see text]
      quantum wires.

PMID- 21727347
TI  - Atomic force microscopy study of the structure-function relationships of the
      biofilm-forming bacterium Streptococcus mutans.
AB  - Atomic force microscopy (AFM) has garnered much interest in recent years for its
      ability to probe the structure, function and cellular nanomechanics inherent to
      specific biological cells. In particular, we have used AFM to probe the important
      structure-function relationships of the bacterium Streptococcus mutans. S. mutans
      is the primary aetiological agent in human dental caries (tooth decay), and is of
      medical importance due to the virulence properties of these cells in biofilm
      initiation and formation, leading to increased tolerance to antibiotics. We have
      used AFM to characterize the unique surface structures of distinct mutants of S.
      mutans. These mutations are located in specific genes that encode surface
      proteins, thus using AFM we have resolved characteristic surface features for
      mutant strains compared to the wild type. Ultimately, our characterization of
      surface morphology has shown distinct differences in the local properties
      displayed by various S. mutans strains on the nanoscale, which is imperative for
      understanding the collective properties of these cells in biofilm formation.

PMID- 21727348
TI  - Vertically aligned carbon nanotube probes for monitoring blood cholesterol.
AB  - Detection of blood cholesterol is of great clinical significance. The
      amperometric detection technique was used for the enzymatic assay of total
      cholesterol. Multiwall carbon nanotubes (MWNTs), vertically aligned on a silicon
      platform, promote heterogeneous electron transfer between the enzyme and the
      working electrode. Surface modification of the MWNT with a biocompatible polymer,
      polyvinyl alcohol (PVA), converted the hydrophobic nanotube surface into a highly
      hydrophilic one, which facilitates efficient attachment of biomolecules. The
      fabricated working electrodes showed a linear relationship between cholesterol
      concentration and the output signal. The efficacy of the multiwall carbon
      nanotubes in promoting heterogeneous electron transfer was evident by distinct
      electrochemical peaks and higher signal-to-noise ratio as compared to the Au
      electrode with identical enzyme immobilization protocol. The selectivity of the
      cholesterol sensor in the presence of common interferents present in human blood,
      e.g. uric acid, ascorbic acid and glucose, is also reported.

PMID- 21727349
TI  - On electron transport in 3D quantum waveguides of variable cross-sections.
AB  - We consider three-dimensional axially symmetric quantum wires with circular cross
      sections whose radius may vary along the axis of the waveguide. In the narrows,
      there arise barriers to the longitudinal motion of an electron. Varying the
      radius, one can create barriers and provide conditions for resonant tunnelling of
      electrons. We suggest a method for numerically studying such phenomena. The
      method can be applied to wires not possessing axial symmetry as well. Besides
      this, we discuss some possible applications.

PMID- 21727350
TI  - Electrochemical characterization of parylene-embedded carbon nanotube
      nanoelectrode arrays.
AB  - A novel parylene-embedded carbon nanotube nanoelectrode array is presented for
      use as an electrochemical detector working electrode material. The fabrication
      process is compatible with standard microfluidic and other MEMS processing
      without requiring chemical mechanical polishing. Electrochemical studies of the
      nanoelectrodes showed that they perform comparably to platinum. Electrochemical
      pretreatment for short periods of time was found to further improve performance
      as measured by cathodic and anodic peak separation of K(3)Fe(CN)(6). A lower
      detection limit below 0.1 uM was measured and with further fabrication
      improvements detection limits between 100 pM and 10 nM are possible. This makes
      the nanoelectrode arrays particularly suitable for trace electrochemical
      analysis.

PMID- 21727351
TI  - Self-aligned immobilization of proteins utilizing PEG patterns.
AB  - A novel self-aligned method to selectively immobilize proteins on a silicon
      dioxide surface is developed in conjunction with a standard lift-off patterning
      technique of a PEG layer. The approach is designed to photolithographically
      pattern regions that specifically bind target proteins and particles, surrounded
      by regions that suppress non-specific attachment of bio-species. The physical and
      biological properties of the derivatized surfaces at the end of the fabrication
      process are characterized.

PMID- 21727352
TI  - Towards ferrofluidics for MU-TAS and lab on-a-chip applications.
AB  - In this paper, we show that ferrofluids can be pumped very effectively in closed
      channel geometries both in the macro- and micro-scales using spatially
      travelling, sinusoidally time-varying magnetic fields. The results from numerical
      modelling demonstrate that the optimum pumping frequency is the reciprocal of the
      Brownian relaxation time constant of the magnetic nanoparticles inside the
      ferrofluid. Since the Brownian time constant depends in part on the overall
      hydrodynamic volume of the magnetic nanoparticles, this work has been carried
      with a view to developing functionalized ferrofluids that can be used as
      sensitive pathogen detectors in the context of ferrohydrodynamic pumping via
      travelling magnetic fields. A micro-ferrofluidic device has been designed and
      fabricated in order to demonstrate the potential development of this technology
      for pathogen detection. A cost-effective fabrication process combining insulated
      metal substrate etching and soft lithography is used to realize the prototype
      micro-ferrofluidic device. Results show good agreement between simulation and
      experiment. We finally propose a ferrofluid-based pathogen detection scheme that
      is expected to be insensitive to temperature and viscosity differences between
      the ferrofluid and the sample to be tested.

PMID- 21727353
TI  - Selective nanoprobes for 'signalling gases'.
AB  - The use of arrays of chemical detectors has been realized in electronic nose
      applications. Recently attention has been focused on the application of e-Noses
      in the medical arena. These are electronic devices that typically employ non
      selective gas sensitive elements for the monitoring of odours and other gaseous
      analytes. Currently, the lack of relative specificity to a mixture of gaseous
      analytes for these sensing elements makes the use of pattern recognition
      algorithms to process the signal and match the acquired data profile to a known
      pattern necessary, thus identifying the signature of the odour or gas detected.
      An alternative approach to chemical detection through the use of small arrays
      (two or three elements) of selective gas sensors made of nanostructured
      semiconducting films and membranes is described in this work. Sensor selectivity
      is defined here as higher sensitivity to a given gas or class of gases in the
      presence of interfering gaseous species. Transition metal oxides are key sensing
      elements of resistive type chemical detectors. A given oxide may be found in
      several polymorph phases, each having a distinct structural configuration. Gas
      oxide interactions are strongly dependent on the 'structure sensitivity' of the
      polymorph used in sensing. This paper reviews the effect of polymorphism on the
      gas specificity and the importance of nanoscale processing for stabilizing the
      desirable oxide phases, and it introduces a gas-polymorph selection library for
      building the next generation of gas sensing systems with inherent selectivity to
      be used as non-invasive disease diagnosis tools.

PMID- 21727354
TI  - A cellular nonlinear network: real-time technology for the analysis of
      microfluidic phenomena in blood vessels.
AB  - A new approach to the observation and analysis of dynamic structural and
      functional parameters in the microcirculation is described. The new non-invasive
      optical system is based on cellular nonlinear networks (CNNs), highly integrated
      analogue processor arrays whose processing elements, the cells, interact directly
      within a finite local neighbourhood. CNNs, thanks to their parallel processing
      feature and spatially distributed structure, are widely used to solve high-speed
      image processing and recognition problems and in the description and modelling of
      biological dynamics through the solution of time continuous partial differential
      equations (PDEs). They are therefore considered extremely suitable for spatial
      temporal dynamic characterization of fluidic phenomena at micrometric to
      nanometric scales, such as blood flow in microvessels and its interaction with
      the cells of the vessel wall. A CNN universal machine (CNN-UM) structure was used
      to implement, via simulation and hardware (ACE16k), the algorithms to determine
      the functional capillarity density (FCD) and red blood cell velocity (RBCV) in
      capillaries obtained by intravital microscopy during in vivo experiments on
      hamsters. The system exploits the moving particles to distinguish the functional
      capillaries from the stationary background. This information is used to
      reconstruct a map and to calculate the velocity of the moving objects.

PMID- 21727355
TI  - Electrolysis-based diaphragm actuators.
AB  - This work presents a new electrolysis-based microelectromechanical systems (MEMS)
      diaphragm actuator. Electrolysis is a technique for converting electrical energy
      to pneumatic energy. Theoretically electrolysis can achieve a strain of 136 000%
      and is capable of generating a pressure above 200 MPa. Electrolysis actuators
      require modest electrical power and produce minimal heat. Due to the large volume
      expansion obtained via electrolysis, small actuators can create a large force. Up
      to 100 um of movement was achieved by a 3 mm diaphragm. The actuator operates at
      room temperature and has a latching and reversing capability.

PMID- 21727356
TI  - A nanoscanning platform for bio-engineering: an in-plane probe with switchable
      stiffness.
AB  - Scanning probe microscopy (SPM) has been one of the most important tools to image
      and, hopefully, to manipulate bio-structures at micro/nanoscales. However, the
      current out-of-plane cantilever design makes it very difficult to extend the
      spectrum of the current SPM technology to meet many new functionalities arising
      from bio-engineering applications. An in-plane scanning probe concept is
      developed to accommodate the new functional requirements. It is designed to have
      a single-strand multi-walled carbon nanotube (CNT) tip assembled at the end of
      the probe, a built-in actuator and a tip deflection sensor, all in the same
      plane. The coplanar design is compatible with most of the standard MEMS processes
      and would facilitate the assembly of a carbon nanotube tip to the micromachined
      probe. The in-plane design features a switchable stiffness which adapts the
      scanning probe's stiffness to the changing surface hardness of the sample. This
      paper describes how the variable stiffness is accomplished by engaging or
      disengaging electrostatically actuated clutches, in addition to the discussions
      on many possible benefits of the in-plane scanning platform.

PMID- 21727357
TI  - Synthesis of and recognition by ribonuclease A imprinted polymers.
AB  - Ribonuclease (RNase), an enzyme which degrades RNA, is ubiquitous in living
      organisms, can renature after autoclaving, and is difficult to inactivate. The
      removal of RNase is especially necessary for the reverse transcription-polymerase
      chain reaction (RT-PCR) and for in vitro transcription and translation.
      Typically, RNase inhibitors must be added to these reactions nowadays.
      Molecularly imprinted polymers (MIPs) could offer many advantages for removal of
      undesired enzymes, including high binding selectivity, stability, low cost, and
      facile synthesis. Surface imprinting, employing immobilized RNase, was used in
      this study to make the most effective use of the template molecules-clearly,
      inaccessible binding sites, no matter how well imprinted, are not useful for
      target binding. Different monomers and cross-linkers were used to synthesize
      RNase-templated MIPs, and the rebinding capacity of each composition was
      characterized. We found that using polyethylene glycol 400 dimethacrylate
      (PEG400DMA) gave the highest imprinting effectiveness (i.e. the highest RNase
      binding ratio between imprinted and non-imprinted polymers). However, including
      styrene monomer (50 wt%) gave polymers with the highest overall affinity for
      ribonuclease A (RNase A). Finally, isothermal titration calorimetry was used as
      an auxiliary tool to help elucidate the mechanisms of the binding of monomers to
      templates, and ligands to MIPs.

PMID- 21727358
TI  - Molecular dynamics simulation of the enhancement of cobra cardiotoxin and E6
      protein binding on mixed self-assembled monolayer molecules.
AB  - Molecular dynamics simulations are performed on n-alkinethiol self-assembled
      monolayers (SAMs) and their mixture on a gold surface so that the orientations of
      the binding of cobra cardiotoxin and E6 protein molecules can be selected using
      the mixing ratio of CH3-terminated SAMs with different chain lengths. The
      simulations suggest that a SAM surface with different mixing ratios may provide a
      possible platform for aligning protein molecules with a desired orientation and
      for enhancing the binding energy of the protein on the designed surface.

PMID- 21727359
TI  - MEMS based hair flow-sensors as model systems for acoustic perception studies.
AB  - Arrays of MEMS fabricated flow sensors inspired by the acoustic flow-sensitive
      hairs found on the cerci of crickets have been designed, fabricated and
      characterized. The hairs consist of up to 1 mm long SU-8 structures mounted on
      suspended membranes with normal translational and rotational degrees of freedom.
      Electrodes on the membrane and on the substrate form variable capacitors,
      allowing for capacitive read-out. Capacitance versus voltage, frequency
      dependence and directional sensitivity measurements have been successfully
      carried out on fabricated sensor arrays, showing the viability of the concept.
      The sensors form a model system allowing for investigations on sensory acoustics
      by their arrayed nature, their adaptivity via electrostatic interaction
      (frequency tuning and parametric amplification) and their susceptibility to noise
      (stochastic resonance).

PMID- 21727360
TI  - Comparative modelling of human beta tubulin isotypes and implications for drug
      binding.
AB  - The protein tubulin is a target for several anti-mitotic drugs, which affect
      microtubule dynamics, ultimately leading to cell cycle arrest and apoptosis. Many
      of these drugs, including the taxanes and Vinca alkaloids, are currently used
      clinically in the treatment of several types of cancer. Another tubulin binding
      drug, colchicine, although too toxic to be used as a chemotherapeutic agent, is
      commonly used for the treatment of gout. The main disadvantage that all of these
      drugs share is that they bind tubulin indiscriminately, leading to the death of
      both cancerous and healthy cells. However, the broad cellular distribution of
      several tubulin isotypes provides a platform upon which to construct novel
      chemotherapeutic drugs that could differentiate between different cell types,
      reducing the undesirable side effects associated with current chemotherapeutic
      treatments. Here, we report an analysis of ten human beta tubulin isotypes and
      discuss differences within each of the previously characterized paclitaxel,
      colchicine and vinblastine binding sites.

PMID- 21727361
TI  - A hybrid mask-mould lithography scheme and its application in nanoscale organic
      thin film transistors.
AB  - Nanoimprint lithography (NIL) has stimulated great interest in both academic
      research and industrial development due to its high resolution, high throughput
      and low cost advantages. Though NIL has been demonstrated to be very successful
      in replicating nanoscale features, it also has its limitations as a general
      lithography technique. Its fundamental moulding characteristics (i.e. physically
      displacing polymer materials) frequently lead to pattern defects when replicating
      arbitrary patterns, especially patterns with broad size distribution. To solve
      this problem, we have developed a combined nanoimprint and photolithography
      technique that uses a hybrid mould to achieve good pattern definitions. In this
      work, we applied this technique to fabricate finger-shaped nanoelectrodes, and
      demonstrated nanoscale pentacene organic thin film transistors (OTFTs). Methods
      of the hybrid mask-mould (HMM) fabrication and results on the device electrical
      characteristics are provided. With combined advantages of both photolithography
      and NIL, and the applicability to general nanoscale device and system
      fabrication, this method can become a valuable choice for low cost mass
      production of micro- and nanoscale structures, devices and systems.

PMID- 21727362
TI  - AFM image reconstruction for deformation measurements by digital image
      correlation.
AB  - The scanner drift of the atomic force microscope (AFM) is a great disadvantage to
      the application of digital image correlation to micro/nano-scale deformation
      measurements. This paper has addressed the image distortion induced by the
      scanner drifts and developed a method to reconstruct AFM images for the
      successful use of AFM image correlation. It presents such a method, that is to
      generate a corrected image from two correlated AFM images scanned at the angle of
      0 degrees  and 90 degrees  respectively. The proposed method has been validated
      by the zero-deformation test. A buckling test of a thin plate under AFM has also
      been demonstrated. The in-plane displacement field at the centre point of the
      buckling plate has been successfully characterized by the application of the
      image correlation technique on reconstructed AFM images.

PMID- 21727363
TI  - Low-pressure detachment nanolithography.
AB  - A simple, one-step method is developed to fabricate various nanostructures such
      as nanoholes and nanolines based on the detachment of an organic polymer film in
      contact with a patterned polyurethane acrylate mould under a low physical
      pressure (1-2 bar) at ambient conditions. Calculation of the work of adhesion
      based on contact angle measurements indicates that the adhesion strength at the
      organic/mould interface is greater than that at the organic/substrate interface,
      resulting in a successful detachment without any surface modifications. 4,4(')
      bis[N-1-napthyl-N-phenyl-amino]biphenyl (NPB) is used as the organic film owing
      to its low cohesion energy and stability in air. Nanoholes as small as 150 nm and
      nanolines as small as 50 nm have been fabricated using this approach. These
      nanostructures are used as a template for selective deposition of silver
      nanoparticles and a wet/dry etch resist for further pattern transfer.

PMID- 21727364
TI  - Novel dandelion-like beta-manganese dioxide microstructures and their magnetic
      properties.
AB  - Single-crystalline dandelion-like beta-MnO(2) three-dimensional microstructures
      have been successfully prepared for the first time via a simple hydrothermal
      process based on the direct reaction between Mn(NO(3))(2) and H(2)O(2). H(2)O(2)
      plays an important role in the formation of the dandelion-like morphology. The
      formation mechanism of the dandelion-like nanostructures was investigated and
      discussed based on the experimental results. Magnetic measurements show that the
      Neel temperature of the as-obtained product is 100 K, which is about 6 K higher
      than that of the corresponding bulk beta-MnO(2) crystals.

PMID- 21727365
TI  - Optical properties of GaN nanorods grown by molecular-beam epitaxy; dependence on
      growth time.
AB  - The growth and optical properties of GaN nanorods grown on Si(111) substrates by
      rf plasma assisted molecular-beam epitaxy are investigated by means of field
      emission scanning electron microscopy and photoluminescence measurements as a
      function of growth time. It is clearly demonstrated that the rate of growth of
      the nanorod diameter starts to increase after ~90 min because of the coalescence
      of neighbouring nanorods. And the optical properties of the samples grown at a
      high growth rate are dramatically changed due to induced defects. The critical
      diameter for defect-free GaN nanorods is determined as below ~140 nm under N-rich
      conditions.

PMID- 21727366
TI  - Highly efficient luminescence from a hybrid state found in strongly quantum
      confined PbS nanocrystals.
AB  - We report that high quality PbS nanocrystals, synthesized in the strong quantum
      confinement regime, have quantum yields as high as 70% at room temperature. We
      use a combination of modelling and photoluminescence up-conversion to show that
      we obtain a nearly monodisperse size distribution. Nevertheless, the emission
      displays a large nonresonant Stokes shift. The magnitude of the Stokes shift is
      found to be directly proportional to the degree of quantum confinement, from
      which we establish that the emission results from the recombination of one
      quantum confined charge carrier with one localized or surface-trapped charge
      carrier. Furthermore, the surface state energy is found to lie outside the bulk
      bandgap so that surface-related emission only commences for strongly quantum
      confined nanocrystals, thus highlighting a regime where improved surface
      passivation becomes necessary.

PMID- 21727367
TI  - Relationships between phase morphology and deformation mechanisms in polymer
      nanocomposite nanofibres prepared by an electrospinning process.
AB  - Relationships between phase morphology and mechanical deformation processes in
      various electrospun polymer nanocomposite nanofibres (PNCNFs) containing
      different types of one-, two- and three-dimensional nanofiller have been
      investigated by transmission electron microscopy using in situ tensile
      techniques. From the study of the phase structure of electrospun PNCNFs, two
      morphological standard types are classified for the analysis of deformation
      mechanisms: the binary system (polymer matrix and nanofillers), and the ternary
      system (polymer matrix, nanofillers and nanopores on the fibres surface).
      According to these categories, deformation processes have been characterized, and
      different schematic models for these processes are proposed. The finding of
      importance in the present work is a brittle-to-ductile transition in polymer
      nanocomposite fibres during in situ tensile deformation processes. This unique
      feature in the deformation behaviour of electrospun PNCNFs provides an optimal
      balance of stiffness, strength and toughness for use as reinforcing elements in a
      polymer based composite of a new kind.

PMID- 21727368
TI  - Enhanced and stable green emission of ZnO nanoparticles by surface segregation of
      Mg.
AB  - The effects of Mg addition on the emission of green photons from ZnO
      nanoparticles were studied. Energy dispersive x-ray spectroscopy (EDS) and Auger
      electron spectroscopy (AES) data demonstrated that ZnO nanoparticles with surface
      segregation of MgO (ZnO:MgO) were precipitated from colloidal reactions between
      Zn(2+),Mg(2+) and OH(-) ions suspended in ethanol. The photoluminescence emission
      spectra showed stronger green emission from suspended ZnO:MgO versus ZnO
      nanoparticles. ZnO:MgO also exhibited a stable green emission colour, which was
      slightly red-shifted from 495 to 520 nm with 168 days of ageing. It was
      postulated that the presence of MgO on the surface of ZnO prevented both the
      aggregation of ZnO nanoparticles via electrostatic stabilization of the
      suspension, and the formation of non-radiative recombination states on the
      surface, resulting in more intense, stable photoemission from ZnO. The red shift
      of the green emission from suspended ZnO nanoparticles with extended ageing was
      attributed to filling of radiative surface trap states in the bandgap.

PMID- 21727369
TI  - NiO nanorings and their unexpected catalytic property for CO oxidation.
AB  - Nickel oxide (NiO) nanorings were synthesized by controllable thermal
      decomposition of precursor Ni(OH)(2) nanoplates obtained via the reaction between
      Ni(NO(3)).6H(2)O and NaOH under hydrothermal conditions. The process of their
      formation was investigated and an unexpected catalytic property of this novel
      shaped material is reported for CO oxidation.

PMID- 21727370
TI  - Tailoring the growth of p-6P nanofibres using ultrathin Au layers: an organic
      metal-dielectric model system.
AB  - The influence of ultrathin Au cluster films on the growth of para-hexaphenyl (p
      6P) fibres is investigated. Whereas p-6P at elevated temperatures forms long,
      mutually parallel fibres on plain mica, these fibres become shorter but taller on
      Au covered mica, up to a Au film thickness of approximately 8 nm. The degree to
      which fibres are mutually parallel decreases with increasing Au thickness. For
      thicker Au films the length of the fibres increases again, and their morphology
      changes from flat to faceted; for Au film thicknesses above 20 nm, fibre networks
      are formed. The spectroscopic properties of the fibres are not modified by the Au
      layer, enabling independent control of the fibre morphology by means of the
      intermediate metallic layer.

PMID- 21727371
TI  - Fabrication and mechanical properties of suspended one-dimensional polymer
      nanostructures: polypyrrole nanotube and helical polyacetylene nanofibre.
AB  - Mechanical properties of suspended quasi-one-dimensional polymer nanostructures
      were investigated using atomic force microscopy (AFM). A recently developed new
      acid-free etch method combined with electron beam lithography was used to
      fabricate suspended polypyrrole (PPy) nanotubes and helical polyacetylene (HPA)
      nanofibres. The elastic modulus of each suspended structure was obtained by AFM
      force-distance measurements. The estimated modulus value of the PPy nanotube (HPA
      nanofibre) was 0.96 GPa (0.5 GPa). Using this acid-free method, all-organic
      flexible NEMS devices can be fabricated in the future.

PMID- 21727372
TI  - Synthesis of framework-substituted Fe-HMS and its catalytic performance for
      phenol hydroxylation.
AB  - The iron-incorporated mesoporous silica material Fe-HMS was successfully
      synthesized at ambient temperature by using dodecylamine as the template agent,
      and it was characterized by XRD, SEM, FT-IR, UV-vis, ESR and N(2) adsorption
      measurements. Its catalytic performance was studied for phenol hydroxylation with
      H(2)O(2) in a fixed-bed reactor. The results show that Fe(3+) ions have been
      successfully incorporated into the framework of HMS, and Fe-HMS has a uniform
      mesoporous structure with about 2.7 nm pore diameter. After Fe-HMS is calcined,
      most of the Fe(3+) ions remain in the tetrahedral coordinated framework, and only
      a small part of Fe species migrate to the extraframework. Fe-HMS has high
      catalytic activity and very high selectivity to dihydroxybenzene for the
      hydroxylation of phenol. Over the Fe-HMS catalyst, the product distribution of
      phenol hydroxylation is different from that over the microporous TS-1 zeolite.
      The solvents have great influence on the catalytic activity of Fe-HMS, and water
      is the best solvent.

PMID- 21727373
TI  - A structural mechanics study of single-walled carbon nanotubes generalized from
      atomistic simulation.
AB  - A new structural mechanics model is developed to closely duplicate the atomic
      configuration and behaviours of single-walled carbon nanotubes (SWCNTs). The
      SWCNTs are effectively represented by a space frame, where primary and secondary
      beams are used to bridge the nearest and next-nearest carbon atoms, to mimic
      energies associated with bond stretching and angle variation, respectively. The
      elastic properties of the frame components are generalized from molecular
      dynamics (MD) simulation based on an accurate ab initio force field, and
      numerical analyses of tension, bending, and torsion are carried out on nine
      different SWCNTs. The space-frame model also closely duplicates the buckling
      behaviours of SWCNTs in torsion and bending. In addition, by repeating the same
      process with continuum shell and beam models, new elastic and section parameters
      are fitted from the MD benchmark experiments. As an application, all three models
      are employed to study the thermal vibration behaviours of SWCNTs, and excellent
      agreements with MD analyses are found. The present analysis is a systematic
      structural mechanics attempt to fit SWCNT properties for several basic
      deformation modes and applicable to a variety of SWCNTs. The continuum models and
      fitted parameters may be used to effectively simulate the overall deformation
      behaviours of SWCNTs at much larger length- and timescales than pure MD analysis.

PMID- 21727374
TI  - Electric field induced growth of well aligned carbon nanotubes from ethanol
      flames.
AB  - This paper introduces a process to synthesize well aligned carbon nanotubes
      (CNTs) from ethanol flames by using a uniform electric field generated from a DC
      power supply. It has been found that (1) comparing with the other processes a
      small electric field is enough to align CNTs; (2) the synthesis process becomes
      more controllable and repeatable; (3) the electric field also improves the
      diameter uniformity and the crystallinity of graphite sheets. It is thought that
      the alignment mechanism is due to the electrostatic force acting upon the
      catalyst particles at the tips of CNTs. The present process has advantages such
      as convenience of applying electric field, simple experiment set-up, and large
      area synthesis of well aligned CNTs.

PMID- 21727375
TI  - Aligned silica nanowires on the inner wall of bubble-like silica film: the growth
      mechanism and photoluminescence.
AB  - Large area, aligned amorphous silica nanowires grow on the inner wall of bubble
      like silica film, which is prepared by thermal evaporation of a molten gallium
      silicon alloy in a flow of ammonia. These nanowires are 10-20 nm in diameter and
      0.5-1.5 um in length. The bubble-like silica film functions as a substrate,
      guiding the growth of silica nanowires by a vapour-solid process. This work helps
      us to clearly elucidate the growth mechanism of aligned amorphous silica
      nanowires, ruling out the possibility of liquid gallium acting as a nucleation
      substrate for the growth of the aligned silica nanowires. A broad emission band
      from 290 to 600 nm is observed in the photoluminescence (PL) spectrum of these
      nanowires. There are seven PL peaks: two blue emission peaks at 430 nm (2.88 eV)
      and 475 nm (2.61 eV); and five ultraviolet emission peaks at 325 nm (3.82 eV),
      350 nm (3.54 eV), 365 nm (3.40 eV), 385 nm (3.22 eV) and 390 nm (3.18 eV), which
      may be related to various oxygen defects.

PMID- 21727376
TI  - Electrospinning processed nanofibrous TiO(2) membranes for photovoltaic
      applications.
AB  - We have recently fabricated dye-sensitized solar cells (DSSCs) comprising
      nanofibrous TiO(2) membranes as electrode materials. A thin TiO(2) film was pre
      deposited on fluorine doped tin oxide (FTO) coated conducting glass substrate by
      immersion in TiF(4) aqueous solution to reduce the electron back-transfer from
      FTO to the electrolyte. The composite polyvinyl acetate (PVac)/titania
      nanofibrous membranes can be deposited on the pre-deposited thin TiO(2) film
      coated FTO by electrospinning of a mixture of PVac and titanium isopropoxide in
      N,N-dimethylformamide (DMF). The nanofibrous TiO(2) membranes were obtained by
      calcining the electrospun composite nanofibres of PVac/titania as the precursor.
      Spectral sensitization of the nanofibrous TiO(2) membranes was carried out with a
      ruthenium (II) complex, cis-dithiocyanate-N,N(')-bis(2,2(')-bipyridyl-4,4(')
      dicarboxylic acid) ruthenium (II) dihydrate. The results indicated that the
      photocurrent and conversion efficiency of electrodes can be increased with the
      addition of the pre-deposited TiO(2) film and the adhesion treatment using DMF.
      Additionally, the dye loading, photocurrent, and efficiency of the electrodes
      were gradually increased by increasing the average thickness of the nanofibrous
      TiO(2) membranes. The efficiency of the fibrous TiO(2) photoelectrode with the
      average membrane thickness of 3.9 um has a maximum value of 4.14%.

PMID- 21727377
TI  - Energy exchanges in carbon nanotube oscillators.
AB  - Energy exchanges between orderly intertube axial motion and vibrational modes are
      studied for isolated systems of two coaxial carbon nanotubes at temperatures
      ranging from 300 to 500 K. It is found that the excess intertube van der Waals
      energy, depleted from the intertube axial motion, is primarily stored in low
      frequency mechanical modes of the oscillator for an extended period of time. This
      constitutes the first computer simulation of a nanomechanical device that
      exhibits negative friction.

PMID- 21727378
TI  - Growth of ZnO nanowires on modified well-aligned carbon nanotube arrays.
AB  - Single-crystal ZnO nanowires were successfully grown on modified well-aligned
      carbon nanotube (CNT) arrays by a hydrothermal process. The pre-deposited ZnO
      grains on the CNTs served as the nucleation sites for the growth of ZnO
      nanowires. The attached growth of ZnO nanowires on the well-aligned CNT arrays
      formed a 3D configuration. The 3D hybrid nanostructured material could find
      application in sensors and other electronic or optoelectronic devices.

PMID- 21727379
TI  - Step-shaped bismuth nanowires with metal-semiconductor junction characteristics.
AB  - Uniform and step-shaped Bi nanowire (NW) arrays have been synthesized by
      electrochemical deposition inside the uniform and step-shaped nanochannels of an
      anodic aluminium oxide template. These Bi NWs are highly oriented and single
      crystalline. The current-voltage characteristics of the parallel uniform Bi
      nanowires show that the contacts between Bi NWs and gold film do not make
      significant contributions to the I-V characteristics of the step-shaped Bi NWs.
      The diameters of the thick segment and the thin segment of the step-shaped Bi NWs
      are about 70 and 40 nm, respectively. Their current-voltage characteristics show
      conventional metal-semiconductor junction behaviour. The approach can be
      exploited to produce one-dimensional metal-semiconductor junctions using step
      shaped NWs consisting of other semi-metals without any external doping, which may
      find various applications in nanotechnology.

PMID- 21727380
TI  - Deterministic shape-selective synthesis of nanowires, nanoribbons and nanosaws by
      steady-state vapour-transport.
AB  - We demonstrate the deterministic shape-selective synthesis and growth of CdSe
      nanowires, nanosaws and nanoribbons by a simple vapour-transport process in a
      tube furnace. The key step, in order to achieve reproducible shape selectivity
      for a given set of deposition parameters, is to exclude any effects of the
      temperature ramping. We prove that an efficient precursor-flow shutter is
      achieved just by varying the total furnace pressure. We then present a shape
      diagram linking the different nanocrystals morphologies to only two parameters:
      powder and substrate temperature. These are varied in the 550-700  degrees C and
      400-600  degrees C range, respectively. A model explaining the shape control is
      discussed.

PMID- 21727381
TI  - Resistor-logic demultiplexers for nanoelectronics based on constant-weight codes.
AB  - The voltage margin of a resistor-logic demultiplexer can be improved
      significantly by basing its connection pattern on a constant-weight code. Each
      distinct code determines a unique demultiplexer, and therefore a large family of
      circuits is defined. We consider using these demultiplexers for building
      nanoscale crossbar memories, and determine the voltage margin of the memory
      system based on a particular code. We determine a purely code-theoretic criterion
      for selecting codes that will yield memories with large voltage margins, which is
      to minimize the ratio of the maximum to the minimum Hamming distance between
      distinct codewords. For the specific example of a 64 * 64 crossbar, we discuss
      what codes provide optimal performance for a memory.

PMID- 21727382
TI  - A self-assembled synthesis of carbon nanotubes for interconnects.
AB  - We report a novel approach to grow highly oriented, freestanding and structured
      carbon nanotubes (CNTs) between two substrates, using microwave plasma chemical
      vapour deposition. Sandwiched, multi-layered catalyst structures are employed to
      generate such structures. The as-grown CNTs adhere well to both the substrate and
      the top contact, and provide a low-resistance electric contact between the two.
      High-resolution scanning electron microscope (SEM) images show that the CNTs grow
      perpendicular to these surfaces. This presents a simple way to grow CNTs in
      different, predetermined directions in a single growth step. The overall
      resistance of a CNT bundle and two CNT-terminal contacts is measured to be about
      14.7 k Omega. The corresponding conductance is close to the quantum limit
      conductance G(0). This illustrates that our new approach is promising for the
      direct assembly of CNT-based interconnects in integrated circuits (ICs) or other
      micro-electronic devices.

PMID- 21727383
TI  - Catalyst-nanostructure interaction and growth of ZnS nanobelts.
AB  - Details of the vapour-liquid-solid Au droplet catalysed growth of ZnS nanobelts
      are elucidated in this work. The inclination of the Au droplet after
      solidification shows that it is indeed in the liquid state during nanobelt
      growth. Numerous stacking faults are observed when (0001) wurtzite is the side
      surface of the nanobelt. Compressive stress at the droplet-nanobelt-atmosphere
      triple interface is the cause of the stacking faults. Sawteeth-like structures
      are observed on the Zn-terminated polar (0001) side surface only. These surfaces
      are chemically active, while S-terminated [Formula: see text] surfaces and non
      polar surfaces are not. On these active surfaces, autocatalysed vapour-solid
      growth leads to the formation of the observed sawteeth.

PMID- 21727384
TI  - Synthesis of Tb(OH)(3) nanowire arrays via a facile template-assisted
      hydrothermal approach.
AB  - Hexagonal wurtzite structure Tb(OH)(3) nanowires with a uniform diameter of about
      70-80 nm and lengths of up to several micrometres have been synthesized on a
      large scale via a hydrothermal treatment based on the use of an anodic aluminium
      membrane as the template. Aligned Tb(OH)(3) nanowire arrays can be obtained by
      dissolving the template. Field emission scanning electron microscopy,
      transmission electron microscopy, high resolution transmission electron
      microscopy, selected area electron diffraction, x-ray diffraction, and
      photoluminescence (PL) spectra have been employed to characterize the as-prepared
      samples. The PL spectrum of Tb(OH)(3) under 350 nm excitation consists of four
      main peaks at 489.9, 543, 584 and 621 nm, among which that for the electric
      dipole transition (5)D(4) to (7)F(5) (at 543 nm) is the strongest. Furthermore, a
      preliminary suggestion for the mechanism of growth of the Tb(OH)(3) nanowires
      using the hydrothermal-template synthesis technique has been proposed.

PMID- 21727385
TI  - Fabrication and photoluminescence of high-quality ternary CdSSe nanowires and
      nanoribbons.
AB  - Ternary alloy CdSSe nanowires and nanoribbons were successfully grown through a
      one-step thermal evaporation route using Au as a catalyst. The nanostructures
      obtained are uniform in diameter, and have smooth surfaces. High-resolution
      transmission electron microscopy, energy dispersive x-ray spectra and x-ray
      diffraction showed that both the nanowires and the nanoribbons have high-quality
      single-crystalline nature, and their compositions can be determined as
      CdS(0.6)Se(0.4) and CdS(0.3)Se(0.7), respectively. The mechanisms of formation of
      these two different nanostructures were discussed. The photoluminescence
      measurements showed very strong band-edge emission for both samples, which
      further demonstrates the single-crystal nature of the as-obtained CdSSe alloys.
      This finding may be extended for fabricating other composition-tunable 1D ternary
      alloy nanostructures.

PMID- 21727386
TI  - Establishing Ohmic contacts for in situ current-voltage characteristic
      measurements on a carbon nanotube inside the scanning electron microscope.
AB  - Multi-walled carbon nanotubes (CNTs), either on an SiO(2) substrate or suspended
      above the substrate, were contacted to W, Au and Pt tips using a nanoprobe
      system, and current-voltage (I-V) characteristics were measured inside a scanning
      electron microscope. Linear I-V curves were obtained when Ohmic contacts were
      established to metallic CNTs. Methods for establishing Ohmic contacts on a CNT
      have been developed using the Joule heating effect when the tips are clean and e
      beam exposing the contacting area of the tip when the tips are covered by a very
      thin contamination layer. When the contact is not good, non-linear I-V curves are
      obtained even though the CNTs that have been contacted are metallic. The
      resistance measured from the metal tip-CNT-metal tip system ranges from 14 to 200
      k Omega. When the CNT was contacted via with Ohmic contacts the total resistance
      of the CNT was found to change roughly linearly with the length of the CNTs
      between the two tips. Field effect measurements were also carried out using a
      third probe as the gate, and field effects were found on certain CNTs with non
      linear I-V characteristics.

PMID- 21727387
TI  - Size effect on the electron-phonon coupling in CuO nanocrystals.
AB  - CuO is the prototype compound of cuprate superconductors, so understanding its
      electronic structures will facilitate the study of the pairing mechanism and
      miscellaneous states of high-temperature superconductors. We prepared uniform CuO
      nanocrystals (7-100 nm) and studied their size-dependent Raman scattering
      spectra. The relative variation between the two-phonon scattering band (2B(g))
      and the one-phonon band (B(g)) indicates a decreasing electron-phonon coupling
      with reducing size, which unveils the dominant Frohlich electron-phonon coupling,
      as indicated by Devreese, but not the small polaron in CuO. Moreover, the
      anomalous enhancement of the multi-phonon band at a critical size and 1D
      structure at room temperature is attributable to an enhanced electron-phonon
      coupling accompanied by phonon-plasmon coupling, i.e., the 'plasphon' proposed by
      Alexandrov et al in 1981.

PMID- 21727388
TI  - On elastic nanoindentation of coated half-spaces by point indenters of non-ideal
      shapes.
AB  - The elastic contact of non-ideal conical and Berkovich indenters with bi-layer
      half-spaces is investigated. Blunted tips are simulated as smooth surfaces. The
      boundary element method is employed to carry out the numerical simulations of
      nanoindentation. An analytical analysis of the influence of the coating thickness
      and the tip bluntness magnitude on the nanoindentation loading curve is realized.
      The dimensionless compression force is introduced in order to describe the
      nanoindentation at different approaches between the indenter and the coated half
      space. A practical technique for determining the Young's modulus of coatings is
      proposed. The technique is based on the modelling of indentation of the blunted
      indenter tip into the coating/substrate composite. This technique is applied to
      the nanoindentation study of nanocrystalline Cr coatings on silicon and glass
      substrates being tested by a diamond Berkovich indenter with a blunted tip.

PMID- 21727389
TI  - Iron changes in natural and Fe(III) loaded montmorillonite during carbon nanotube
      growth.
AB  - A detailed elaboration of the transformations of iron species, present in natural
      and Fe(NO(3))(3) loaded montmorillonite, during carbon deposition and carbon
      nanotube growth is described. According to transmission electron microscopy
      results, deposited carbon atoms form fibres in the case of pristine
      montmorillonite and multiwalled carbon nanotubes in the case of Fe(III) loaded
      montmorillonite. Mossbauer and x-ray diffraction analysis results point to an
      extensive reduction of structural and intercalated Fe(III) cations to Fe(II) with
      the latter migrating from the interlayer space to the vacant octahedral sites of
      the mineral's lattice. Such migration of the non-structural iron catalyst
      prohibits extensive contamination of the final composite with various metal
      catalyst impurities. The crucial role of the active catalytic centres in the
      formation of carbon nanotubes is ascribed to a minor quantity of iron, found
      entrapped in the carbon nanostructures, which, at the end of the reaction, is
      identified as iron carbide. The interesting formation of a nanometric gamma-iron
      precipitate is also detected, which is probably stabilized through strong
      interactions with the lattice of montmorillonite. Finally, it is demonstrated
      that iron-rich natural clay minerals can serve as direct catalysts for carbon
      nanotube growth.

PMID- 21727390
TI  - Finite element characterization of the size-dependent mechanical behaviour in
      nanosystems.
AB  - Mechanical behaviour analysis plays an important role in the design of micro/nano
      electromechanical system (MEMS/NEMS) devices for reliability. In this paper, the
      size-dependent mechanical properties of nanostructures are numerically studied
      with the finite element method (FEM) by developing a kind of surface element to
      take into account the surface elastic effect. This method is then applied to the
      investigation of the interaction between two pressurized nanovoids and the
      effective moduli of two-dimensional nanoporous material. The numerical results
      indicate that surface elasticity can significantly alter the nature of
      interaction forms and the effective moduli by inducing a strong size dependence
      in conventional results.

PMID- 21727391
TI  - Electrospinning of polymer nanofibres from multiple jets on a porous tubular
      surface.
AB  - A novel method for the electrospinning of multiple polymer jets into nanofibres
      is presented. In this work, 20 wt% nylon 6 solution was electrified and pushed by
      air pressure through the walls of a porous polyethylene tube. Multiple jets
      formed on the porous surface and electrospun into nanoscale fibres. The length
      weighted fibre diameters have a similar mean diameter to those from a single jet
      but broader in distribution. The mass production rate from the porous tube is 250
      times greater than from a typical single jet.

PMID- 21727392
TI  - Effect of material anisotropy on the self-positioning of nanostructures.
AB  - An experimental and numerical investigation of the effect of material anisotropy
      on the self-positioning of epitaxial nanostructures has been performed. The self
      positioning occurs due to a lattice mismatch between two epitaxial material
      layers (GaAs and In(0.2)Ga(0.8)As) of a hinge. Both materials have cubic crystal
      symmetry and possess anisotropic mechanical properties. The dependence of the
      hinge curvature radius on the material orientation angle was obtained
      experimentally by creating self-positioning hinges with different angles between
      the hinge axis and material crystallographic axes. The same self-positioning
      structures were modelled by solving geometrically nonlinear problems with the
      help of the finite element method. Experimental and numerical values of the hinge
      curvature radius are in qualitative agreement. It is found that material
      anisotropy significantly affects the shape of self-positioning structures.

PMID- 21727393
TI  - Template synthesis and forming electrical contacts to single Au nanowires by
      focused ion beam techniques.
AB  - Metallic Au nanowires were electrochemically synthesized in 20 um thick ion track
      etched polycarbonate membranes with the nominal pore diameter of 200 nm. Scanning
      and transmission electron microscopy analysis and x-ray diffraction of samples
      revealed that the nanowires are dense with a fcc [Formula: see text] texturing.
      The I-V characteristics of a single Au nanowire were investigated using a four
      point microprobe set-up. The Au nanowire was placed in electrical contact with
      electrodes patterned on planar substrates using a dual-beam focused ion beam
      technique. The resistivity of the Au nanowires was found to be 2.8 * 10(-4) Omega
      cm.

PMID- 21727394
TI  - Corrugated surfaces formed on GaAs(331)A substrates: the template for laterally
      ordered InGaAs nanowires.
AB  - Morphology evolution of high-index GaAs(331)A surfaces during molecular beam
      epitaxy (MBE) growth has been investigated in order to achieve regularly
      distributed step-array templates and fabricate spatially ordered low-dimensional
      nano-structures. Atomic force microscope (AFM) measurements have shown that the
      step height and terrace width of GaAs layers increase monotonically with
      increasing substrate temperature. By using the step arrays formed on GaAs(331)A
      surfaces as the templates, we have fabricated highly ordered InGaAs nanowires.
      The improved homogeneity and the increased density of the InGaAs nanowires are
      attributed to the modulated strain field caused by vertical multi-stacking, as
      well as the effect of corrugated surface of the template. Photoluminescence (PL)
      tests confirmed remarkable polarization anisotropy.

PMID- 21727395
TI  - A controllable synthesis of multi-armed CdTe nanorods.
AB  - A simple, productive and low-cost route has been developed to synthesize multi
      armed CdTe nanorods using myristic acid (MA) as a complex agent. The yield of
      this approach can reach 75%. The dimension of the multi-armed nanorods can be
      controlled by tuning the molar ratios of Cd/Te and Cd/MA; the diameter can be
      changed from 2 to 7 nm while the length from 15 to 60 nm. The hexagonal structure
      was confirmed in x-ray diffraction analysis. However, it was assumed that one
      crystal is composed of the dominant hexagonal structure along with a cubic
      structure in the core.

PMID- 21727396
TI  - Correlation between photoluminescence and Fourier transform infrared spectra in
      tetra-ethyl-ortho-silicate thin films.
AB  - We report strong visible photoluminescence (PL) from thermally treated tetra
      ethyl-ortho-silicate (TEOS) thin films at room temperature. High-resolution
      transmission electron microscope (HRTEM) studies showed that the PL originated
      from nanocrystalline-Si (nc-Si). HRTEM images showed that as-grown TEOS thin
      films had quasi-static amorphous (QSA) SiO(2) phases instead of the typical
      amorphous (TA) SiO(2) phases, and that they divided into small pieces of nc-Si
      after thermal treatment. In addition, Fourier transform infrared (FTIR)
      investigations showed that the QSA-SiO(2) phases were composed of three types of
      bonding modes (i.e., Si-O-Si bending, Si-O bending, and Si-O-Si stretching),
      which play important roles in the formation of the nc-Si at relatively lower
      annealing temperatures.

PMID- 21727397
TI  - Titanium monomers and wires adsorbed on carbon nanotubes: a first principles
      study.
AB  - In this work a theoretical study of Ti monomers and wires interacting with an (8,
      0) semiconductor single-wall carbon nanotube (SWNT), by inside as well as outside
      faces, is presented. Spin-polarized total-energy ab initio calculations, based on
      the density functional theory, are used to describe the structural, electronic
      and magnetic properties of the studied systems. The most stable configurations
      for monomers are found to be over the centre of a C-C bond for inside and over
      the midpoint of the centre of the hexagonal site for outside. Considering that
      the Ti atoms on the tube surface tend to form continuous wires, to allow a
      comprehensive view of the interaction of the Ti wires with the SWNT surface, we
      present a complete understanding, both from inside and outside the nanotube. Our
      calculations have shown that the most stable configuration is with the wire
      inside the tube, with the resulting electronic structures showing a metallic
      system with high hybridization between the Ti and C atoms and a large charge
      transfer from Ti to C atoms. For Ti wire adsorbed inside the tube the low spin
      configuration is shown to be more stable than high spin configuration and the
      opposite behaviour is observed for the corresponding outside case. These novel
      results are relevant for the understanding of Ti atoms covering and filling
      SWNTs, demonstrating the high stability of these systems and suggesting that they
      can be useful for future use in nanodevices, in particular for spintronics and
      nanosensors.

PMID- 21727398
TI  - Nanopatterned self-assembled monolayers.
AB  - We report on the fabrication of chemically nanopatterned gold surfaces by
      combining electron-beam lithography with gas and liquid phase thiolization. The
      line-edge roughness of the patterns is ~4 nm, corresponding to a limiting feature
      size in the range of 15 nm. Indications for a lower packing density of the self
      assembled monolayers grown in the nanofeatures are given, and evidences for the
      bleeding of thiols along the grain boundaries of the gold substrate are
      displayed. A comparison is provided between nanopatterned thiol and silane
      monolayers on gold and on silicon wafers, respectively. The line-edge roughnesses
      are shown to be close to each other for these two systems, indicating that the
      limiting step is currently the lithography step, suggesting possible improvement
      of the resolution. The advantages and drawbacks of thiol versus silane monolayers
      are finally discussed with respect to the formation of chemically nanopatterned
      surfaces.

PMID- 21727399
TI  - Towards creation of iron nanodots using metastable atom lithography.
AB  - Iron structures with dimensions of the order of the minimum domain size (~50 nm
      at room temperature) may provide us with a new high-density data storage method.
      Limitations have been observed in existing depositional atom lithography schemes
      for producing these structures. We present a proof-in-principle experiment using
      an alternative scheme based upon direct exposure metastable neon-atom
      lithography. Iron structures with dimensions of the order of 7.5 um are produced
      by this method. Extension of this work to the application of standing-wave atom
      lithography and laser cooling flux enhancement techniques is discussed as a
      method for reducing dimensions to a size equating to a dot array density of
      around 0.1 Gbit mm(-2).

PMID- 21727400
TI  - Frequency modulated atomic force microscopy on MgO(001) thin films:
      interpretation of atomic image resolution and distance dependence of tip-sample
      interaction.
AB  - Atomically resolved images on a MgO(001) thin film deposited on Ag(001) obtained
      in ultrahigh vacuum by frequency modulated atomic force microscopy at low
      temperature are presented and analysed. Images obtained in the attractive regime
      show a different type of contrast formation from those acquired in the repulsive
      regime. For the interpretation of the image contrast we have investigated the tip
      sample interaction. Force and energy were recovered from frequency shift versus
      distance curves. The derived force curves have been compared to the force laws of
      long-range, short-range and contact forces. In the attractive regime close to the
      minimum of the force-distance curve elastic deformations have been confirmed. The
      recovered energy curve has been scaled to the universal Rydberg model, yielding a
      decay length of l = 0.3 nm and DeltaE = 4.2 aJ (26 eV) for the maximum adhesion
      energy. A universal binding-energy-distance relation is confirmed for the
      MgO(001) thin film.

PMID- 21727401
TI  - Ordered growth and local workfunction measurements of tris(8-hydroxyquinoline)
      aluminium on ultrathin KBr films.
AB  - In this work we investigate the growth of tris(8-hydroxyquinoline) aluminium
      (Alq(3)) on single-crystal Ag(111) substrates partially covered by an ultrathin
      KBr film. Noncontact atomic force microscopy is used to determine the molecular
      ordering of 0.8 monolayer Alq(3) evaporated onto these substrates. The
      simultaneous measurement of the local surface potential by means of Kelvin probe
      force microscopy yields the local workfunction difference between the pure
      Ag(111) surface and the one covered by an ultrathin KBr film, by pure Alq(3), or
      by both (KBr|Alq(3)). The molecular ordering and the interface dipole formation
      are discussed with respect to experiments described in the literature in which
      electron diffraction and photoelectron spectroscopy were used, respectively.

PMID- 21727402
TI  - Differentiation of molecules in a mixed self-assembled monolayer of H-and Cl
      terminated bicyclo[2.2.2]octane derivatives.
AB  - H- and Cl-terminal groups of bicyclo[2.2.2]octane (BCO) derivatives in a mixed
      self-assembled monolayer (SAM) on Au(111) were imaged using a modified Si tip
      with a CaF(2) nanocluster to differentiate the two terminals, which have
      different electronegativities. In order to achieve this we fabricated a new
      sample holder, on which a CaF(2) single crystal and the mixed SAM on Au(111)
      could be mounted side by side. We transferred the holder with the two samples
      into a ultrahigh vacuum (UHV) atomic force microscopy (AFM) chamber. Upon
      cleaving the CaF(2) single crystal under UHV, a fresh and clean CaF(2)(111)
      surface parallel with the SAM surface appeared within 2 mm of the separation. The
      modified Si tip was prepared by repeatedly making contact between a Si tip and
      the CaF(2)(111) surface. The resulting modified tip could image the atomic
      periodicity of a Ca(2+) and an F(-) sublattice on the CaF(2)(111) surface
      depending on the sign of the tip-terminating ion, i.e. an F(-) and a Ca(2+) ion,
      respectively, as reported previously (Foster et al 2002 Phys. Rev. B 66 235417).
      Using the modified Si tip with the known tip-terminating ion, we observed the Cl
      terminal in the surrounding H-terminals in the mixed SAM by noncontact (NC) AFM.
      Here, the Cl-terminal is negatively charged due to its electronegativity and thus
      the BCO moiety with the Cl-terminal is terminated by a C(delta+)-Cl(delta-)
      permanent dipole, while the H-terminal is almost neutral. The Cl-terminal
      appeared brighter (more attractive) and darker (more repulsive) than the
      surrounding H-terminals in NC-AFM images depending on the sign of the tip
      terminating ion, i.e. a Ca(2+) and an F(-) on the modified tip, respectively,
      although the relationship between the image contrast and the sign of the tip
      terminating ion was not always perfect because of the instability of the tip
      terminating ion on the nanocluster. The present method can be used to distinguish
      terminal groups with different electronegativities.

PMID- 21727403
TI  - Imaging nanoclusters in the constant height mode of the dynamic SFM.
AB  - For the first time, high quality images of metal nanoclusters which were recorded
      in the constant height mode of a dynamic scanning force microscope (dynamic SFM)
      are shown. Surfaces of highly ordered pyrolytic graphite (HOPG) were used as a
      test substrate since metal nanoclusters with well defined and symmetric shapes
      can be created by epitaxial growth. We performed imaging of gold clusters with
      sizes between 5 and 15 nm in both scanning modes, constant Deltaf mode and
      constant height mode, and compared the image contrast. We notice that clusters in
      constant height images appear much sharper, and exhibit more reasonable lateral
      shapes and sizes in comparison to images recorded in the constant Deltaf mode.
      With the help of numerical simulations we show that only a microscopically small
      part of the tip apex (nanotip) is probably the main contributor for the image
      contrast formation. In principle, the constant height mode can be used for
      imaging surfaces of any material, e.g. ionic crystals, as shown for the system
      Au/NaCl(001).

PMID- 21727404
TI  - Nanodomain manipulation for ultrahigh density ferroelectric data storage.
AB  - Nanosized inverted domain dots in ferroelectric materials have potential
      application in ultrahigh density rewritable data storage systems. Herein, a data
      storage system is presented based on scanning non-linear dielectric microscopy
      and a thin film of ferroelectric single-crystal lithium tantalite. Through domain
      engineering, we succeeded in forming our smallest artificial nanodomain single
      dot at 5.1 nm diameter and an artificial nanodomain dot array with a memory
      density of 10.1 Tbit inch(-2) and a bit spacing of 8.0 nm, representing the
      highest memory density for rewritable data storage reported to date.
      Subnanosecond (500 ps) domain switching speed has also been achieved. Next,
      actual information storage with a low bit error and high memory density was
      performed. A bit error ratio of less than 1 * 10(-4) was achieved at an areal
      density of 258 Gbit inch(-2). Moreover, actual information storage is
      demonstrated at a density of 1 Tbit inch(-2).

PMID- 21727405
TI  - Non-contact atomic force microscopy study of atomic manipulation on an insulator
      surface by nanoindentation.
AB  - Experimental results on vertical manipulation on an insulator surface using non
      contact atomic force microscopy are presented. Cleaved ionic KCl(100) single
      crystal is used as an insulator surface. With the nanoindentation method used,
      the vertical manipulation of a single atom in an ionic crystal surface is more
      difficult than in a semiconductor surface. Therefore, in many cases, more than
      one surface atom is manipulated while, in rare cases, single-atom manipulation is
      successfully performed. Lateral manipulation of a vacancy has occasionally
      succeeded on the KCl(100) surface. We have presumed that the lateral manipulation
      was induced by pulling.

PMID- 21727406
TI  - Lateral manipulation of atomic size defects on the CaF(2)(111) surface.
AB  - Atomic scale manipulation on insulating surfaces is one of the great challenges
      of non-contact atomic force microscopy. Here we demonstrate lateral manipulation
      of defects occupying single ionic sites on a calcium fluoride (111)-surface.
      Defects stem from the interaction of the residual gas with the surface. The
      process of surface degradation is briefly discussed. Manipulation is performed
      over a wide range of path lengths ranging from tens of nanometres down to a few
      lattice constants. We introduce a simple manipulation protocol based on line-by
      line scanning of a surface region containing defects to be manipulated, and
      record tip-surface distance and cantilever resonance frequency detuning as a
      function of the manipulation pathway in real time. We suggest a hopping model to
      describe manipulation where the tip-defect interaction is governed by repulsive
      forces.

PMID- 21727407
TI  - Kelvin probe force microscopy on surfaces of UHV cleaved ionic crystals.
AB  - Force spectroscopy and Kelvin probe force microscopy (KPFM) measurements taken on
      (001) surfaces of UHV cleaved NaCl, KCl and MgO are presented for the first time.
      With the help of force spectroscopy we show first that the charging of (001)
      surfaces of alkali halide crystals, which generally occurs after UHV cleavage,
      vanishes after a couple of days due to their sufficiently high ionic conductivity
      at room temperature. KPFM images of these (001) surfaces show that the surface
      potential is not uniform but exhibits variations of up to 1 V at a nanometre
      length scale. Variations on terraces as well as a strong contrast at step edges
      can be observed, of which the latter is probably due to trapped charges. On
      MgO(001), we observe strong changes in the surface potential, especially at
      previously reported adstructures. These changes explain why imaging MgO(001) is
      difficult.

PMID- 21727408
TI  - Three-dimensional observation of nanoscale ferroelectric domains using scanning
      nonlinear dielectric microscopy with electric field correction by Kelvin probe
      force microscopy.
AB  - An advanced technique for the measurement of three-dimensional ferroelectric
      domain structure is described. Scanning nonlinear dielectric microscopy is used
      to measure the polarization components both perpendicular and parallel to the
      specimen surface. A nanoscale electric field correction is devised and performed
      using Kelvin probe force microscopy to allow more precise measurement of the
      nanoscale polarization component parallel to the specimen surface. Using this
      electric field correction, three-dimensional imaging of the ferroelectric
      polarization orientation is demonstrated.

PMID- 21727409
TI  - Measuring phase shifts and energy dissipation with amplitude modulation atomic
      force microscopy.
AB  - By recording the phase angle difference between the excitation force and the tip
      response in amplitude modulation AFM it is possible to image compositional
      variations in heterogeneous samples. In this contribution we address some of the
      experimental issues relevant to perform phase contrast imaging measurements.
      Specifically, we study the dependence of the phase shift on the tip-surface
      separation, interaction regime, cantilever parameters, free amplitude and tip
      surface dissipative processes. We show that phase shift measurements can be
      converted into energy dissipation values. Energy dissipation curves show a
      maximum (~10 eV/cycle) with the amplitude ratio. Furthermore, energy dissipation
      maps provide a robust method to image material properties because they do not
      depend directly on the tip-surface interaction regime. Compositional contrast
      images are illustrated by imaging conjugated molecular islands deposited on
      silicon surfaces.

PMID- 21727410
TI  - Novel amplitude and frequency demodulation algorithm for a virtual dynamic atomic
      force microscope.
AB  - Frequency-modulated atomic force microscopy (FM-AFM; also called non-contact
      atomic force microscopy) is the prevailing operation mode in (sub-)atomic
      resolution vacuum applications. A major obstacle that prohibits a wider
      application range is the low frame capture rate. The speed of FM-AFM is limited
      by the low bandwidth of the automatic gain control (AGC) and frequency
      demodulation loops. In this work we describe a novel algorithm that can be used
      to overcome these weaknesses. We analysed the settling times of the proposed
      loops and that of the complete system, and we found that an approximately 70-fold
      improvement can be achieved over the existing real and virtual atomic force
      microscopes. We show that proportional-integral-differential controllers perform
      better in the frequency demodulation loop than conventional proportional-integral
      controllers. We demonstrate that the signal to noise ratio of the proposed system
      is 5.7 * 10(-5), which agrees with that of the conventional systems; thus, the
      new algorithm would improve the performance of FM-AFMs without compromising the
      resolution.

PMID- 21727411
TI  - A study of the topographic and electrical properties of self-assembled islands of
      alkylsilanes on mica using a combination of non-contact force microscopy
      techniques.
AB  - We use a combination of non-contact scanning force microscope operation modes to
      study the changes in topographic and electrostatic properties of self-assembled
      monolayer islands of alkylsilanes on mica. The combined technique uses
      simultaneous electrical and mechanical modulation and feedback modes to produce
      four images that reveal the topography, phase, surface potential and dielectric
      constant. The results show significant advantages with this combined method. As
      an example we show that the interaction of water with self-assembled monolayer
      islands of alkylsilanes produces changes in the surface potential of the system
      but not in the topography.

PMID- 21727412
TI  - Visualization of charges stored in the floating gate of flash memory by scanning
      nonlinear dielectric microscopy.
AB  - By applying scanning nonlinear dielectric microscopy (SNDM), we succeeded in
      clarifying that electrons existed in the poly-Si layer of the floating gate of a
      flash memory. The charge accumulated in the floating gate can be detected by SNDM
      as a change in the capacitance of the poly-Si (floating gate) by scanning the
      surface of the SiO(2)-SiN(4)-SiO(2) (ONO) film covering the floating gate. There
      was a clear black contrast region in the SNDM image of the floating gate area,
      where electrons were injected. However, no clear contrast appeared in the
      floating gate where electrons were not injected. We confirmed that SNDM is one of
      the most useful methods of observing the charge accumulated in flash memory.

PMID- 21727413
TI  - Force microscopy experiments with ultrasensitive cantilevers.
AB  - Force microscopy experiments with the pendulum geometry are performed with
      attonewton sensitivity (Rugar et al 2004 Nature 43 329). Single-crystalline
      cantilevers with sub-millinewton spring constants were annealed under ultrahigh
      vacuum conditions. It is found that annealing with temperatures below 500 
      degrees C can improve the quality factor by an order of magnitude. The high force
      sensitivity of these ultrasoft cantilevers is used to characterize small magnetic
      and superconductive particles, which are mounted on the end of the cantilever.
      Their magnetic properties are analysed in magnetic fields as a function of
      temperature. The transition of a superconducting sample mounted on a cantilever
      is measured by the detection of frequency shifts. An increase of dissipation is
      observed below the critical temperature. The magnetic moment of ferromagnetic
      particles is determined by real time frequency detection with a phase-locked loop
      (PLL) as a function of the magnetic field. The dissipation between the probing
      tip and the sample is another important ingredient for ultrasensitive force
      measurements. It is found that dissipation increases at separations of 30 nm. The
      origins of this type of dissipation are poorly understood. However, it is
      predicted theoretically that adsorbates can increase this dissipation channel
      (Volokitin and Persson 2005 Phys. Rev. Lett. 94 086104). First experiments are
      performed under ultrahigh vacuum to investigate this type of dissipation. Long
      range dissipation is closely related to long-range forces. The distance
      dependence of the contact potential is found to be an important aspect.

PMID- 21727414
TI  - Possibility of imaging lateral profiles of individual tetrahedral hybrid orbitals
      in real space.
AB  - The imaging mechanism of scanning tunnelling microscopy (STM) and non-contact
      atomic force microscopy (NC-AFM) has the same origin, that is, the interaction
      between the electronic states of the tip and the electronic states of the sample.
      Therefore, using a well-characterized sample, the tip electronic states become
      the object to be probed by both STM and AFM. In this paper, we will present an
      analytic approach to compute the force distribution and the tunnelling
      conductance distribution. As an example, we predict the possibility of resolving
      the lateral profiles of the tetrahedral hybrid orbitals, which are the foundation
      of many important materials essential to industry and life. We will discuss the
      conditions under which it could be observed, together with the issue of
      reproducibility.

PMID- 21727415
TI  - Shear-mode magnetic force microscopy with a quartz tuning fork in ambient
      conditions.
AB  - We have demonstrated high-resolution shear-mode magnetic force microscopy (MFM)
      using a quartz tuning fork in ambient conditions. A commercial magnetic
      cantilever tip was attached to one prong of the tuning fork to realize shear-mode
      MFM operation. We have obtained MFM images with a spatial resolution of less than
      100 nm and demonstrated a frequency resolution of ~1 mHz, values which are
      achieved by phase shift detection methods.

PMID- 21727416
TI  - Models of atomic scale contrast in dissipation images of binary ionic surfaces in
      non-contact atomic force microscopy.
AB  - Using model ionic systems and the recently proposed theory of dynamical response
      at close approach (Kantorovich and Trevethan 2004 Phys. Rev. Lett. 93 236102) in
      non-contact atomic force microscopy (NC-AFM), we present the results of
      calculations performed to investigate the formation of atomic scale contrast in
      dissipation images. The accessible energy states and barriers of the microscopic
      tip-surface system are determined as a function of tip position above the
      surface. These are then used along with typical experimental parameters to
      investigate the dynamical response of the system and mechanisms of atomic scale
      contrast. We show how the damping signal contrast can appear either correlated or
      anti-correlated with the topography depending on the distance of closest approach
      and the system temperature. The dependence of the dissipated energy, and the
      reversibility of a structural change, on the tip frequency and system temperature
      is investigated and the relevance of this to single-atom manipulation with the NC
      AFM is discussed.

PMID- 21727417
TI  - Chaos in dynamic atomic force microscopy.
AB  - In tapping mode atomic force microscopy (AFM) the highly nonlinear tip-sample
      interaction gives rise to a complicated dynamics of the microcantilever. Apart
      from the well-known bistability under typical imaging conditions the system
      exhibits a complex dynamics at small average tip-sample distances, which are
      typical operation conditions for mechanical dynamic nanomanipulation. In order to
      investigate the dynamics at small average tip sample gaps experimental time
      series data are analysed employing nonlinear analysis tools and spectral
      analysis. The correlation dimension is computed together with a bifurcation
      diagram. By using statistical correlation measures such as the Kullback-Leibler
      distance, cross-correlation and mutual information the dataset can be segmented
      into different regimes. The analysis reveals period-3, period-2 and period-4
      behaviour, as well as a weakly chaotic regime.

PMID- 21727418
TI  - Imaging of biomaterials in liquids: a comparison between conventional and Q
      controlled amplitude modulation ('tapping mode') atomic force microscopy.
AB  - Lambda phage DNA and DPPC thin films are imaged in liquids by atomic force
      microscopy applying the amplitude modulation mode ('tapping mode') with active
      enhancement of the Q-factor by a 'Q-control' electronics. The topography of the
      resulting images is compared with images obtained without active Q-control. To
      enable a meaningful comparison, individual scan lines are alternately recorded
      with and without Q-factor enhancement using scan parameters optimized for each
      mode separately. As the major finding, significant height differences of
      topographical features are observed between the two modes. The heights measured
      with active Q-control are reproducibly higher compared to the ones observed
      without Q enhancement. This effect is attributed to the reduction of tip-sample
      forces by Q-control.

PMID- 21727419
TI  - Labelling of cells with quantum dots.
AB  - Colloidal quantum dots are semiconductor nanocrystals well dispersed in a
      solvent. The optical properties of quantum dots, in particular the wavelength of
      their fluorescence, depend strongly on their size. Because of their reduced
      tendency to photobleach, colloidal quantum dots are interesting fluorescence
      probes for all types of labelling studies. In this review we will give an
      overview on how quantum dots have been used so far in cell biology. In particular
      we will discuss the biologically relevant properties of quantum dots and focus on
      four topics: labelling of cellular structures and receptors with quantum dots,
      incorporation of quantum dots by living cells, tracking the path and the fate of
      individual cells using quantum dot labels, and quantum dots as contrast agents.

PMID- 21727420
TI  - Time-resolved photoluminescence spectroscopy of ligand-capped PbS nanocrystals.
AB  - PbS nanocrystals are synthesized using colloidal techniques and have their
      surfaces capped with oleic acid. The absorption band edge of the PbS nanocrystals
      is tuned between 900 and 580 nm. The PbS nanocrystals exhibit tuneable
      photoluminescence with large non-resonant Stokes shifts of up to 500 meV. The
      magnitude of the Stokes shift is found to be dependent upon the size of PbS
      nanocrystals. Time-resolved photoluminescence spectroscopy of the PbS
      nanocrystals reveals that the photoluminescence has an extraordinarily long
      lifetime of 1 us. This long fluorescence lifetime is attributed to the effect of
      dielectric screening similar to that observed in other IV-VI semiconductor
      nanocrystals.

PMID- 21727421
TI  - Spindly cobalt ferrite nanocrystals: preparation, characterization and magnetic
      properties.
AB  - In this paper we describe the preparation of homogeneously needle-shaped cobalt
      ferrite (CoFe(2)O(4)) nanocrystals on a large scale through the smooth
      decomposition of urea and the resulting co-precipitation of Co(2+) and Fe(3+) in
      oleic acid micelles. Furthermore, we found that other ferrite nanocrystals with a
      needle-like shape, such as zinc ferrite (ZnFe(2)O(4)) and nickel ferrite
      (NiFe(2)O(4)), can be prepared by the same process. Needle-shaped CoFe(2)O(4)
      nanocrystals dispersed in an aqueous solution containing oleic acid exhibit
      excellent stability and the formed colloid does not produce any precipitations
      after two months, which is of prime importance if these materials are applied in
      magnetic fluids. X-ray diffraction (XRD) measurements were used to characterize
      the phase and component of the co-precipitation products, and demonstrate that
      they are spinel ferrite with a cubic symmetry. Transmission electron microscopy
      (TEM) observation showed that all the nanocrystals present a needle-like shape
      with a 22 nm short axis and an aspect ratio of around 6. Varying the
      concentration of oleic acid did not bring about any obvious influence on the size
      distribution and shapes of CoFe(2)O(4). The magnetic properties of the needle
      shaped CoFe(2)O(4) nanocrystals were evaluated by using a vibrating sample
      magnetometer (VSM), electron paramagnetic resonance (EPR), and a Mossbauer
      spectrometer, and the results all demonstrated that CoFe(2)O(4) nanocrystals were
      superparamagnetic at room temperature.

PMID- 21727422
TI  - The oscillatory damped behaviour of incommensurate double-walled carbon
      nanotubes.
AB  - The mechanical properties of sliding carbon nanotubes have been investigated by
      classical molecular dynamics simulations in the canonical ensemble. In particular
      we have studied damped oscillations in the separation between the centres of mass
      of the inner and outer tubes of double-walled carbon nanotubes (DWCN).
      Incommensurate DWCNs forming (7, 0)@(9, 9) structures were simulated for systems
      at 298.15 K with axial lengths from 12.21 to 98.24 nm. The oscillations exhibited
      frequencies in the range of gigahertz with the frequency decreasing as the length
      of the system increases. The time until oscillations become negligible exhibited
      a nearly linear dependence on the length of the system. Two macroscopic models
      were developed in order to understand the forces involved in terms of macroscopic
      properties like friction and shear. The first model considered constant restoring
      forces during the whole event, while in the second the value of these constant
      restoring forces depended on the initial conditions of each oscillation. Both
      models reproduced the oscillations quite well, while the second model allows us
      to predict the dynamic shear strength in terms of the axial length of the system
      for tubes with the same diameters. The calculated dynamic shear strength
      exhibited monotonic behaviour with an inverse dependence on the length of the
      system. For systems with unequal axial lengths, the restoring force, which drives
      the oscillation, is reduced compared to the system with equal lengths, regardless
      of whether the outer nanotube is longer or shorter.

PMID- 21727423
TI  - Contact force identification using the subharmonic resonance of a contact-mode
      atomic force microscopy.
AB  - We propose a step-by-step experimental procedure for characterization of the
      nonlinear contact stiffness on surfaces using contact-mode atomic force
      microscopy. Our approach directly estimates the first-, second-, and third-order
      coefficients of the contact stiffness. It neither uses nor requires the
      underlying assumptions of the Hertzian contact theory. We use a primary resonance
      excitation of the probe to estimate the linear coefficient of the contact
      stiffness. We use the method of multiple scales to obtain closed-form expressions
      approximating the response of the probe to a subharmonic resonance excitation of
      order one-half. We utilize these expressions and higher-order spectral
      measurements to independently estimate the quadratic and cubic coefficients of
      the contact stiffness.

PMID- 21727424
TI  - Structure and properties of electrospun PLLA single nanofibres.
AB  - An electrospinning method was used to spin semi-crystalline poly(L-lactide)
      (PLLA) nanofibres. Processing parameter effects on the internal molecular
      structure of electrospun PLLA fibres were investigated by x-ray diffraction (XRD)
      and differential scanning calorimetry (DSC). Take-up velocity was found as a
      dominant parameter to induce a highly ordered molecular structure in the
      electrospun PLLA fibres compared to solution conductivity and polymer
      concentration, although these two parameters played an important role in
      controlling the fibre diameter. A collecting method of a single nanofibre by an
      electrospinning process was developed for the tensile tests to investigate
      structure-property relationships of the polymer nanofibres. The tensile test
      results indicated that higher take-up velocity caused higher tensile modulus and
      strength due to the ordered structure developed through the process.

PMID- 21727425
TI  - Nanostructure and magnetic properties of the MnZnO system, a room temperature
      magnetic semiconductor?
AB  - The magnetic properties of the system MnZnO prepared by conventional ceramic
      procedures using ZnO and MnO(2) starting powders are studied and related to the
      nanostructure. Thermal treatment at 500  degrees C produces a ferromagnetic
      phase, although this temperature is not high enough to promote proper sintering;
      thus the thermally treated compact shows brittle characteristics of unreacted and
      poorly densified ceramic samples. Scanning electron microscopy and x-ray analysis
      reveal the appearance of a new phase, most probably related to the diffusion of
      Zn into MnO(2) oxide nanocrystals. The magnetic properties deviate considerably
      from what would be expected of an unreacted mixture of ZnO (diamagnetic) and
      MnO(2) particles (paramagnetic above 100 K and anti-ferromagnetic below that
      temperature), exhibiting a ferromagnetic like behaviour from 5 to 300 K and
      beyond mixed with a paramagnetic component. The ferromagnetic phase seems to be
      originated by diffusion at the nanoscale of Zn into MnO(2) grains. The Curie
      temperature of the ferromagnetic phase, once the paramagnetic component has been
      subtracted from the hysteresis loops, is measured to be 450 K. EPR resonance
      experiments from 100 to 600 K confirm a ferromagnetic to paramagnetic like
      transition above room temperature for these materials.

PMID- 21727426
TI  - Transport and photodetection in self-assembled semiconductor quantum dots.
AB  - A great step forward in science and technology was made when it was discovered
      that lattice mismatch can be used to grow highly ordered, artificial atom-like
      structures called self-assembled quantum dots. Several groups have in the
      meantime successfully demonstrated useful infrared photodetection devices which
      are based on this technology. The new physics is fascinating, and there is no
      doubt that many new applications will be found when we have developed a better
      understanding of the underlying physical processes, and in particular when we
      have learned how to integrate the exciting new developments made in nanoscopic
      addressing and molecular self-assembly methods with semiconducting dots. In this
      paper we examine the scientific and technical questions encountered in current
      state of the art infrared detector technology and suggest ways of overcoming
      these difficulties. Promoting simple physical pictures, we focus in particular on
      the problem of high temperature detector operation and discuss the origin of dark
      current, noise, and photoresponse.

PMID- 21727427
TI  - Electronic transport properties of carbon nanotube based
      metal/semiconductor/metal intramolecular junctions.
AB  - The electronic structure and the conductance of a carbon nanotube based
      metal/semiconductor/metal intramolecular junction is investigated numerically.
      The nature of electronic states at the interfaces and in the semiconductor
      section is analysed. The quantum conductance of the system is calculated in the
      coherent regime and its variations with energy and length are shown to be related
      to contributions from different kinds of electronic state.

PMID- 21727428
TI  - Calibration of silicon atomic force microscope cantilevers.
AB  - We present a comparison of three different methods to calibrate the spring
      constant of two different types of silicon beam shaped atomic force microscope
      (AFM) cantilevers to determine each method's accuracy, ease of use and potential
      destructiveness. The majority of research in calibrating AFM cantilevers has been
      concerned with contact mode levers. The two types of levers we have studied are
      used in force modulation and tapping mode in air. Not only can these types of
      cantilevers have spring constants an order of magnitude greater than contact mode
      levers, but also their geometries can be quite different from the standard V
      shape contact lever. In this work we experimentally determine the correction
      factors for two of the calibration methods when applied to the tapping mode
      cantilevers and also demonstrate that the force modulation levers can be
      calibrated easily and accurately using these same techniques.

PMID- 21727429
TI  - First-principles calculation of the conductance of a single 4,4 bipyridine
      molecule.
AB  - The conductance of a single 4,4 bipyridine (44BPD) molecule connected to two gold
      electrodes is calculated using a density functional theory based Green function
      method. The atomic geometry of such a molecular junction is constructed from the
      optimized structure of a gold trimer-44BPD-gold trimer complex. Resonant
      conduction is the main feature of its transport properties. The magnitude of the
      transmission coefficient at the Fermi level is determined to be T = 1.01 * 10(
      2), which is in excellent agreement with the experimental value. The dependence
      of the transmission on the Au-N bond length and the torsion angle is also
      discussed.

PMID- 21727430
TI  - Synthesis of single-crystal manganese dioxide nanowires by a soft chemical
      process.
AB  - alpha- and beta-MnO(2) single-crystal nanowires have been successfully
      synthesized through a soft chemical process, which involves no catalysts or
      templates. The diameters of the nanowires are about 10-40 nm and the lengths up
      to several tens of micrometres. Experimental results showed that MnO(2)
      polymorphic forms can be synthesized by selected-control reaction temperatures
      and their crystal phases in the nanowires were confirmed by XRD and TEM
      measurement. Further, the formation process of nanowires is discussed.

PMID- 21727431
TI  - An investigation into the melting of silicon nanoclusters using molecular
      dynamics simulations.
AB  - Using the Stillinger-Weber (SW) potential model, we have performed molecular
      dynamics (MD) simulations to investigate the melting of silicon nanoclusters
      comprising a maximum of 9041 atoms. This study investigates the size, surface
      energy and root mean square displacement (RMSD) characteristics of the silicon
      nanoclusters as they undergo a heating process. The numerical results reveal that
      an intermediate nanocrystal regime exists for clusters with more than 357 atoms.
      Within this regime, a linear relationship exists between the cluster size and its
      melting temperature. It is found that melting of the silicon nanoclusters
      commences at the surface and that T(m,N) = T(m,Bulk)-alphaN(-1/3). Therefore, the
      extrapolated melting temperature of the bulk with a surface decreases from
      T(m,Bulk) = 1821 K to a value of T(m,357) = 1380 K at the lower limit of the
      intermediate nanocrystal regime.

PMID- 21727432
TI  - Redox-active monolayers on nano-scale silicon electrodes.
AB  - Uniform arrays of nano-scale electrolyte-molecule-silicon capacitors have been
      successfully fabricated. This was done by a combination of reactive ion etch and
      a selective wet etch through an anodic aluminium oxide mask to form nano-holes in
      silicon oxide/silicon nitride insulator layers on silicon. Self-assembled
      monolayers of 4-ferrocenylbenzyl alcohol were then attached to the exposed
      silicon surfaces at the bottom of the nano-holes. Characterization by
      conventional capacitance and conductance techniques showed very high capacitance
      and conductance peaks near -0.6 V, that were attributed to the charging and
      discharging of electrons into and from discrete levels in the monolayer owing to
      the presence of the redox-active ferrocenes.

PMID- 21727433
TI  - High-voltage SPM oxidation of ZrN: materials for multiscale applications.
AB  - Scanning probe microscope (SPM) oxidation was used to form zirconium oxide
      features on 200 nm thick ZrN films. The features exhibit rapid yet controlled
      growth kinetics, even in contact mode with 70 V dc applied between the probe tip
      and substrate. The features grown for times longer than 10 s are higher than 200
      nm, and reach more than 1000 nm in height after 300 s. Long-time oxidation
      experiments and selective etching of the oxides and nitrides lead us to propose
      that as the oxidation reaches the silicon substrate, delamination occurs with the
      simultaneous formation of a thin layer of new material at the ZrN/Si interface.
      High-voltage oxide growth on ZrN is fast and sustainable, and the robust oxide
      features are promising candidates for multiscale (nanometre-to-micrometre)
      applications.

PMID- 21727434
TI  - Morphologies and microstructures of nano-sized Cu(2)O particles using a
      cetyltrimethylammonium template.
AB  - Hollow polyhedra and cubes of nanostructured Cu(2)O particles have been
      synthesized by reduction of CuSO(4) with ascorbate acid in the solution phase.
      The nanostructures were obtained when the cetyltrimethylammonium (CTAB)
      concentration ranged from 0 to 0.03 M in the presence of NaOH. Structural
      characterizations, by means of x-ray photoelectron spectroscopy (XPS) for
      measuring Cu valence states and by electron microscopy for microstructure and
      chemical analyses, suggest that most Cu(2)O nanoparticles are covered with a thin
      CuO shell arising possibly from reaction of the adsorbed oxygen on the Cu(2)O
      particle surface. The blue shift is observed as microstructures of Cu(2)O
      nanoparticles changed from cubic to hollow in ultraviolet and visible (UV
      visible) absorption spectra. Both the Cu(2)O hollow and cubic nanostructures show
      certain quantum-confined effects. A cationic CTAB template mechanism is proposed
      to interpret the formation of the Cu(2)O nanoparticles.

PMID- 21727435
TI  - On the thermal annealing conditions for self-synthesis of tungsten carbide
      nanowires from WC(x) films.
AB  - The thermal annealing conditions in nitrogen ambient for the self-synthesis of
      tungsten carbide nanowires from sputter-deposited WC(x) films were investigated.
      Experimental results show that the temperature window for the growth of nanowires
      lies in the range of 500-750  degrees C with the corresponding annealing time
      interval ranging from 2.5 to 0.25 h. The diameter, length, and density of the
      grown nanowires are in the range of 10-15 nm, 0.1-0.3 um, and 210-410 um(-2),
      respectively. The degree of carbon depletion in the annealed WC(x) films plays a
      crucial role in determining both the shape and density of the self-synthesized
      nanowires. Nanowires synthesized at lower temperatures were seen to be smaller in
      dimension but higher in density. Material analysis reveals that the phase
      transition from WC to W(2)C arising from decarburization of the WC(x) film during
      thermal annealing should be responsible for the self-synthesis of nanowires.

PMID- 21727436
TI  - Selective etching of metallic single-wall carbon nanotubes with hydrogen plasma.
AB  - We present Raman scattering and scanning tunnelling microscopy (STM) measurements
      on hydrogen plasma etched single-wall carbon nanotubes (SWNTs). Interestingly,
      both the STM and Raman spectroscopy show that the metallic SWNTs are dramatically
      altered and highly defected by the plasma treatment. In addition, structural
      characterizations show that metal catalysts are detached from the ends of the
      SWNT bundles. For semiconducting SWNTs we observe no feature of defects or
      etching along the nanotubes. Raman spectra in the radial breathing mode region of
      plasma-treated SWNT material show that most of the tubes are semiconducting.
      These results show that hydrogen plasma treatment favours etching of metallic
      nanotubes over semiconducting ones and therefore could be used to tailor the
      electronic properties of SWNT raw materials.

PMID- 21727437
TI  - Controlled synthesis of LaPO(4) and CePO(4) nanorods/nanowires.
AB  - LaPO(4) and CePO(4) nanorods/nanowires with controlled aspect ratios have been
      successfully synthesized using a hydrothermal microemulsion method under mild
      conditions. It has been shown that the obtained LaPO(4) has a monoclinic
      structure, while CePO(4) exists in the hexagonal structure. Uniform
      nanorods/nanowires with diameters of 20-60 nm and lengths ranging from several
      hundreds of nanometres to several micrometres were obtained. The aspect ratios of
      the obtained 1D nanostructures can be fine-tuned by simply changing the [H(2)O
      ]/[surfactant] molar ratios. The possible growth mechanism of LaPO(4) and CePO(4)
      nanorods/nanowires was explored in detail.

PMID- 21727438
TI  - Synthesis of CoPt nanoparticles by a modified polyol method: characterization and
      magnetic properties.
AB  - CoPt nanoparticles with an average size of 3 nm and narrow distribution were
      synthesized by chemical reduction of Co(CH(3)COO)(2) and Pt(acac)(2) by
      polyethyleneglycol-200. The as-prepared nanoparticles have a disordered fcc
      structure which transformed after thermal treatment to an ordered fct structure,
      which results in coercivity up to 6 kOe at room temperature and 9 kOe at 5 K
      because of the high magnetocrystalline anisotropy of the tetragonal structure
      [Formula: see text].

PMID- 21727439
TI  - Orientation-enhanced growth and optical properties of ZnO nanowires grown on
      porous silicon substrates.
AB  - ZnO nanowires have been synthesized on porous silicon substrates with different
      porosities via the vapour-liquid-solid method. The texture coefficient analysed
      from the XRD spectra indicates that the nanowires are more highly orientated on
      the appropriate porosity of porous silicon substrate than on the smooth surface
      of silicon. The Raman spectrum reveals the high quality of the ZnO nanowires.
      From the temperature-dependent photoluminescence spectra, we deduced the
      activation energies of free and bound excitons.

PMID- 21727440
TI  - The influence of the tip structure and the electric field on BN nanocones.
AB  - Different configurations for BN nanocones with 240 degrees  disclination are
      analysed through first-principles calculations based on the density-functional
      theory. The studied cone tips involve either four pentagons with two homonuclear
      bonds or two squares and two hexagons with no homonuclear bonds. The structures
      are both terminated by two three-coordinated atoms. Cohesive energy results show
      that the cone terminated in pentagons is slightly energetically preferred. The
      influence of a 1.7 V A(-1) external electric field, applied along the axis, on
      the structural changes and charge distributions is analysed. The responses of the
      charge distributions to the external electric field demonstrate the main role
      played by the B atoms for the applications of BN cones as probes in electronic
      microscopy as well as field emitters.

PMID- 21727441
TI  - Longitudinal photocurrent spectroscopy of a single GaAs/AlGaAs v-groove quantum
      wire.
AB  - Modulation-doped GaAs v-groove quantum wires (QWRs) have been fabricated with
      novel electrical contacts made to two-dimensional electron-gas (2DEG) reservoirs.
      Here, we present longitudinal photocurrent (photoconductivity/PC) spectroscopy
      measurements of a single QWR. We clearly observe conductance in the ground-state
      one-dimensional subbands; in addition, a highly temperature-dependent response is
      seen from other structures within the v-groove. The latter phenomenon is
      attributed to the effects of structural topography and localization on carrier
      relaxation. The results of power-dependent PC measurements suggest that the QWR
      behaves as a series of weakly interacting localized states, at low temperatures.

PMID- 21727442
TI  - Electro-orientation in particle light valves.
AB  - Electro-orientation of rod-like particles in liquids, under the application of an
      external AC field, is analysed. A rod shape is suitable for particle light valve
      (PLV) applications. When they are aligned with their long axes parallel to the
      electric field (and the direction of light is assumed to be parallel to the
      applied electric field), then it can lead to good transmission of light. Various
      criteria to arrive at appropriate parameters for PLV applications are proposed.
      It is found that good electric conductors are excellent rod materials for PLV
      applications. They lead to an appropriate orientation of the rods and at the same
      time result in maximum orientational torque. Water-like liquids with higher
      values of permittivity are appropriate choices as suspending liquids since the
      Brownian dispersion in the presence of the electric field is minimized. The time
      it takes the rods to fully diffuse in the orientational space, once the electric
      field is turned off, decreases with decreasing liquid viscosity.

PMID- 21727443
TI  - Electrochemical growth of ZnO nanoplates.
AB  - ZnO films were grown on polycrystalline Zn foil by cathodic electrodeposition in
      an aqueous zinc chloride/calcium chloride solution at 80  degrees C. Variation in
      the electrochemical parameters resulted in a variation in growth morphology from
      1D (nanorods), 2D ('nanoplates') to 3D crystal growth. An as-received or
      mechanically polished substrate proved the most suitable substrate finish and
      allowed more highly aligned, dense structures to be grown; in contrast,
      electropolished substrates formed inhomogeneous deposits. Substrate annealing
      gave rise to large homogenous areas of nanorod deposition. Two-dimensional sheet
      growth was found to occur in conjunction with nanorods under specific
      electrochemical conditions. Hexagonal 'plates' approximately 50 nm in thickness
      and several microns in diameter were formed normal to the substrate.

PMID- 21727444
TI  - [Formula: see text] <-> (3 * 3) phase transition in Pb/Ge(111) and Sn/Ge(111): a
      phenomenological study on the phase transition anomalies and the role of defects.
AB  - A phenomenological study of the [Formula: see text] phase transitions occurring
      in the adsorption systems Pb/Ge(111) and Sn/Ge(111) is presented. The starting
      point of such a study is the Landau theory. The critical behaviour expected
      theoretically for the two interfaces, and the corresponding influence of defects,
      are discussed in detail. Symmetry arguments show that, contrary to general
      belief, the critical behaviours of Pb/Ge(111) and Sn/Ge(111) are essentially
      different. The Landau-like approach employed to study the influence of defects
      provides a consistent and general manner to interpret the existing experimental
      data. Special attention is paid to the influence of hopping defects in
      Sn/Ge(111).

PMID- 21727445
TI  - A photochemical method for controlling the size of CdS nanoparticles.
AB  - The optical and electrical properties of semiconductor nanoparticles are strongly
      dependent on their size. A flexible control of the size of the nanoparticles is
      of interest for tuning their properties for different applications. Here we use a
      coupled method to control the size of CdS nanoparticles. The method involves the
      photochemical growth of CdS nanoparticles together with the use of a capping
      agent as an inhibiting factor. CdS nanoparticles were formed through a
      photoinduced reaction of CdSO(4) and Na(2)S(2)O(3) in an aqueous solution.
      Mercaptoethanol (C(2)H(6)OS) was used as the capping agent, and we investigated
      the effect of illumination time, illumination intensity and the concentration of
      capping agent on the nanoparticle size. Transmission electron microscopy (TEM)
      shows crystalline nanoparticles with relatively low dispersion. Optical
      absorption spectroscopy was mainly used to measure the band gap and size of the
      nanoparticles. Increasing the illumination time or illumination intensity
      increases the nanoparticle size, while higher capping agent concentration leads
      to smaller nanoparticle size. A band gap range of 2.75-3.4 eV was possible with
      our experimental conditions, corresponding to a 3.2-6.0 nm size range.

PMID- 21727446
TI  - Electrochemical machining with ultrashort voltage pulses: modelling of charging
      dynamics and feature profile evolution.
AB  - A two-dimensional computational model is developed to describe electrochemical
      nanostructuring of conducting materials with ultrashort voltage pulses. The model
      consists of (1) a transient charging simulation to describe the evolution of the
      overpotentials at the tool and workpiece surfaces and the resulting dissolution
      currents and (2) a feature profile evolution tool which uses the level set method
      to describe either vertical or lateral etching of the workpiece. Results
      presented include transient currents at different separations between tool and
      workpiece, evolution of overpotentials and dissolution currents as a function of
      position along the workpiece, and etch profiles as a function of pulse duration.

PMID- 21727447
TI  - Detection and identification of nucleic acid engineered fluorescent labels in
      submicrometre fluidic channels.
AB  - Nucleic acid engineers have created nanoscale fluorescent labels that are
      uniquely identifiable by the number of conjugated fluorophores, and with binding
      characteristics that permit recognition of individual specific biomolecules. The
      viability of this technology for use in multi-analyte homogeneous assays depends
      on the ability to optically detect individual labels, and distinguish the
      fluorescence emission of each label. We describe the use of fluidic channels with
      submicrometre dimensions to rapidly detect individual labels in solution. Labels
      with small differences in fluorophore composition were differentiated with
      varying degrees of accuracy. Labels were synthesized at the molecular level from
      dendrimer-like DNA, with the identity encoded into the number of Alexa Fluor 488
      and BODIPY 630/650 fluorophores conjugated with the structure. To explore the
      decoding resolution limit, labels with a single fluorophore of each colour were
      detected, and were found to be distinguishable as a group, but not individually,
      from labels with one additional red fluorophore. Labels with one green and three
      red fluorophores were individually distinguishable with greater than 80% accuracy
      from labels with one red and three green fluorophores. Photon counting histograms
      were analysed to differentiate the various labels, and fluorescence correlation
      spectroscopy was used to measure their mobilities. Fluidic channels were
      fabricated in fused silica with a 500 nm square cross section, resulting in a
      focal volume of approximately 500 al. Because the entire channel width was
      illuminated, every fluorescent molecule in solution passing through the channel
      was uniformly excited and analyzed. Flow control enabled a balance of rapid data
      acquisition and efficient fluorescence collection with these nanoscale systems.

PMID- 21727448
TI  - Graphoepitaxy of cylinder-forming block copolymers for use as templates to
      pattern magnetic metal dot arrays.
AB  - We report a method to fabricate high-quality patterned magnetic dot arrays using
      block copolymer lithography, metal deposition, and a dry lift-off technique. Long
      range order of cylindrical domains oriented perpendicular to the substrate and in
      hexagonal arrays was induced in the block copolymer films by prepatterning the
      substrate with topographic features and chemically modifying the surface to
      exhibit neutral wetting behaviour towards the blocks of the copolymer. The
      uniformity of the domain size and row spacing of block copolymer templates
      created in this way was improved compared to those reported in previous studies
      that used graphoepitaxy of sphere-forming block copolymers. The pattern of block
      copolymer domains was transferred to a pattern of magnetic metal dots,
      demonstrating the potential of this technology for the fabrication of patterned
      magnetic recording media.

PMID- 21727449
TI  - Computational modelling of multiscale morphologies in polymer-liquid crystal
      blends.
AB  - Simulations of material architectures in polymer-liquid crystal blends driven by
      phase separation-phase ordering-texturing processes are presented. The study
      shows that mixtures of polymers and liquid crystals result in blend morphologies
      that organize at several scales. For thermally driven instabilities, morphologies
      of polymer droplets embedded in a liquid crystal matrix show colloidal
      crystallinity. Large polymer drops strongly affect the orientation of the matrix,
      producing textures consisting of defect lattices. This work shows that thermally
      driven phase separation-phase ordering-texturing processes can result in
      multiscale materials, with length scales cascading down from droplets to
      interfaces, and finally to nanoscale defects.

PMID- 21727450
TI  - Anti-reflective optical coatings incorporating nanoparticles.
AB  - This paper presents a simple approach for forming anti-reflective film stacks on
      plastic substrates employing aqueous colloidal dispersions of metal oxide
      nanoparticles. Results demonstrate that it is possible to fabricate a polymeric
      thin film of continuously tunable refractive index over a wide range by loading
      the film with varying concentrations of metal oxide nanoparticles. Specifically,
      the refractive index for the polymer film was tuned from 1.46 to 1.54 using
      silica nanoparticle loadings from 50 to 0 wt% and from 1.54 to 1.95 using ceria
      nanoparticle loadings from 0 to 90 wt%, respectively. The low and high refractive
      index layers are then combined to create an anti-reflective coating which
      exhibits a reflectance spectrum, abrasion resistance, haze and transmission
      values that compare well with those produced using state-of-the-art vacuum based
      techniques. Furthermore, the results show that it is possible to begin with
      aqueous dispersions and then dilute them with organic solvents for use in a spin
      coating method to prepare the polymer-metal oxide nanoparticle composite films.

PMID- 21727451
TI  - Size- and shape-controlled synthesis of colloidal gold through autoreduction of
      the auric cation by poly(ethylene oxide)-poly(propylene oxide) block copolymers
      in aqueous solutions at ambient conditions.
AB  - Gold nanoparticles with an average diameter in the range 5-20 nm have been
      synthesized from hydrogen tetrachloroaureate (III) hydrate (HAuCl(4).3H(2)O) in
      air-saturated aqueous PEO-PPO-PEO block copolymer solutions at ambient
      temperature in the absence of any other reducing agent (PEO: poly(ethylene
      oxide), PPO: poly(propylene oxide)). The particle size was controlled by the
      block copolymer concentration and PEO and PPO block lengths. Our findings
      indicate that longer PEO blocks lead to an increase in particle size because of
      an increase in reaction activity. Adsorption of PO segments on gold nanoparticles
      seems to prevent particle growth from aggregation, and results in small particle
      size and high colloidal stability. An increase of the HAuCl(4) concentration
      causes a change in the particle shape from spherical to triangular or hexagonal
      nanoplates.

PMID- 21727452
TI  - Formation of nanoparticles in flames; measurement by particle mass spectrometry
      and numerical simulation.
AB  - The size distributions of nanoparticles in flames are measured using a novel
      particle mass spectrometer (PMS), which is developed for the size range between
      0.3 and 50 nm and for number concentrations between 10(9) and 10(13). Using this
      instrument the particles are sampled without prior dilution from the flame into a
      molecular beam. The charged nanoparticles are then deflected by an electric
      field, to determine the mass according to the time-of-flight principle. The PMS
      is installed in a low pressure combustion chamber operated at 30 mbar.
      Measurements are made on primary soot particles and iron oxide particles in a
      laminar, premixed acetylene/oxygen flame. The soot particles increase in size as
      a function of the height above the burner and the C/O ratio from 2 up to 10 nm.
      Iron oxide particles of 3-5 nm are detected as a function of burner height. The
      soot particles form more rapidly than the iron oxide particles. A model
      calculation for the formation of silica and iron oxide in hydrogen/oxygen flames
      is developed, based on previously published reaction mechanisms. On adding a mono
      disperse particle coagulation scheme, the time history of the particle number
      concentration and the particle size is calculated. In agreement with experimental
      data, the calculations show that iron oxide particles are formed more slowly than
      silica particles.

PMID- 21727453
TI  - Carbon microtubes: tuning internal diameters and conical angles.
AB  - In this paper, we report a synthesis strategy for a new class of hollow, curved
      carbon morphologies, 'carbon microtubes' (CMTs), with absolute control over their
      conical angles and internal diameters. Our synthesis methodology employs nitrogen
      or oxygen dosing to change the wetting behaviour of gallium metal with the
      growing carbon walls to tune the conical angles. Increasing N(2) concentrations
      in the gas phase during growth increases the conical angles of CMTs from +25
      degrees  to about -20 degrees . A methodology using the timing of oxygen or
      nitrogen dosing during CMT growth is shown to tune the internal diameters
      anywhere from a few nanometres to a few microns. The walls of the carbon
      microtubes are characterized using transmission electron microscopy (TEM) and
      Raman spectroscopy and are found to consist of aligned graphite nanocrystals (2-5
      nm in size). Furthermore, dark field images of CMTs showed that the graphite
      nanocrystals are aligned with their c-axes perpendicular to the wall surface and
      that the crystals themselves are oriented with respect to the wall surface
      depending upon the conical angle of the CMT.

PMID- 21727454
TI  - Direct growth of core-shell SiC-SiO(2) nanowires and field emission
      characteristics.
AB  - A simple, direct synthesis method was used to grow core-shell SiC-SiO(2)
      nanowires by heating NiO-catalysed silicon substrates. A carbothermal reduction
      of WO(3) provided a reductive environment and carbon source to synthesize
      crystalline SiC nanowires covered with SiO(2) sheaths at the growth temperature
      of 1000-1100  degrees C. Transmission electron microscopy showed that the SiC
      core was 15-25 nm in diameter and the SiO(2) shell layer was an average of 20 nm
      in thickness. The thickness of the SiO(2) shell layer could be controlled using
      hydrofluoric acid (HF) etching. Field emission results of core-shell SiC-SiO(2)
      and bare SiC nanowires showed that the SiC nanowires coated with an optimum
      SiO(2) thickness (10 nm) have a higher field emission current than the bare SiC
      nanowires.

PMID- 21727455
TI  - Conformal nanocoating of zirconia nanoparticles by atomic layer deposition in a
      fluidized bed reactor.
AB  - Primary zirconia nanoparticles were conformally coated with alumina ultrathin
      films using atomic layer deposition (ALD) in a fluidized bed reactor. Alternating
      doses of trimethylaluminium and water vapour were performed to deposit Al(2)O(3)
      nanolayers on the surface of 26 nm zirconia nanoparticles. Transmission Fourier
      transform infrared spectroscopy was performed ex situ. Bulk Al(2)O(3) vibrational
      modes were observed for coated particles after 50 and 70 cycles. Coated
      nanoparticles were also examined with transmission electron microscopy, high
      resolution field emission scanning electron microscopy and energy dispersive
      spectroscopy. Analysis revealed highly conformal and uniform alumina nanofilms
      throughout the surface of zirconia nanoparticles. The particle size distribution
      and surface area of the nanoparticles are not affected by the coating process.
      Primary nanoparticles are coated individually despite their high aggregation
      tendency during fluidization. The dynamic aggregation behaviour of zirconia
      nanoparticles in the fluidized bed plays a key role in the individual coating of
      nanoparticles.

PMID- 21727456
TI  - Preparation of biocatalytic nanofibres with high activity and stability via
      enzyme aggregate coating on polymer nanofibres.
AB  - We have developed a unique approach for the fabrication of enzyme aggregate
      coatings on the surfaces of electrospun polymer nanofibres. This approach employs
      covalent attachment of seed enzymes onto nanofibres consisting of a mixture of
      polystyrene and poly(styrene-co-maleic anhydride), followed by a glutaraldehyde
      (GA) treatment that cross-links additional enzyme molecules and aggregates from
      the solution onto the covalently attached seed enzyme molecules. These cross
      linked enzyme aggregates, covalently attached to the nanofibres via the linkers
      of seed enzyme molecules, are expected to improve the enzyme activity due to
      increased enzyme loading, and also the enzyme stability. To demonstrate the
      principle, we coated alpha-chymotrypsin (CT) on nanofibres electrospun from a
      mixture of polystyrene and poly(styrene-co-maleic anhydride). The initial
      activity of CT-aggregate-coated nanofibres was nine times higher than nanofibres
      with just a layer of covalently attached CT molecules. The enzyme stability of CT
      aggregate-coated nanofibres was greatly improved with essentially no measurable
      loss of activity over a month of observation under rigorous shaking conditions.
      This new approach of enzyme coating on nanofibres, yielding high activity and
      stability, creates a useful new biocatalytic immobilized enzyme system with
      potential applications in bioconversion, bioremediation, and biosensors.

PMID- 21727457
TI  - Synthesis of germanium nanocrystals in high temperature supercritical CO(2).
AB  - Germanium nanocrystals were synthesized in supercritical (sc) CO(2) by
      thermolysis of diphenylgermane (DPG) or tetraethylgermane (TEG) with octanol as a
      capping ligand at 500  degrees C and 27.6 MPa. The Ge nanocrystals were
      characterized with high resolution transmission electron microscopy (HRTEM),
      energy-dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD). On the
      basis of TEM, the mean diameters of the nanocrystals made from DPG and TEG were
      10.1 and 5.6 nm, respectively. The synthesis in sc-CO(2) produced much less
      organic contamination compared with similar reactions in organic supercritical
      fluids. When the same reaction of DPG with octanol was performed in the gas phase
      without CO(2) present, bulk Ge crystals were formed instead of nanocrystals.
      Thus, the solvation of the hydrocarbon ligands by CO(2) was sufficient to provide
      steric stabilization. The presence of steric stabilization in CO(2) at a reduced
      temperature of 2.5, with a reduced solvent density of only 0.4, may be attributed
      to a reduction in the differences between ligand-ligand interactions and ligand
      CO(2) interactions relative to thermal energy.

PMID- 21727458
TI  - Deposition of platinum nanoparticles on organic functionalized carbon nanotubes
      grown in situ on carbon paper for fuel cells.
AB  - Deposition of small Pt nanoparticles of the order of 2-2.5 nm on carbon nanotubes
      (CNTs) grown directly on carbon paper is demonstrated in this work. Sulfonic acid
      functionalization of CNTs is used as a means to facilitate the uniform deposition
      of Pt on the CNT surface. The organic molecules attached covalently to the CNT
      surface via electrochemical reduction of corresponding diazonium salts are
      treated with concentrated sulfuric acid and the sulfonic acid sites thus attached
      are used as molecular sites for Pt ion adsorption, which are subsequently reduced
      to yield the small Pt nanoparticles. Cyclic voltammograms reveal that, after
      removal of the organic groups during high temperature reduction, these Pt
      nanoparticles are in electrical contact with the carbon paper backing. A typical
      Pt loading of 0.09 mg cm(-2) is achieved, that shows higher specific surface area
      of Pt than an E-TEK electrode with Pt loading of 0.075 mg cm(-2). A membrane and
      electrode assembly (MEA) is prepared with a Pt/CNT electrode as cathode and an E
      TEK electrode as anode, and it offers better performance than a conventional E
      TEK MEA.

PMID- 21727459
TI  - Engineering high-temperature stable nanocomposite materials.
AB  - The low thermal stability of nanoparticles typically restricts their use in
      catalytic and other applications to low- to moderate-temperature conditions. We
      present a novel approach to the stabilization of nanosized noble metal particles
      by embedding them in a high-temperature stabilized hexa-aluminate matrix. The
      simple 'one-pot' approach is based on a microemulsion-templated sol-gel synthesis
      and yields mesoporous nanocomposite materials with pure textural porosity and
      excellent high-temperature stability up to about 1200  degrees C. To our
      knowledge, this is the first time that metal nanoparticles have been stabilized
      to such high temperatures. We furthermore find that the microemulsion templating
      allows a tailoring of the ceramic matrix without influencing the size of the
      embedded Pt particle. This opens up the possibility of a true multiscale
      engineering of nanocomposite materials. We see these novel materials therefore
      not only as very promising candidates for a broad range of high-temperature
      catalytic applications, but generally view this versatile synthesis route as a
      first step towards expanding the parameter range for nanoparticle applications.

PMID- 21727460
TI  - Brownian dynamics study of polymer-stabilized nanoparticles.
AB  - A Brownian dynamics simulation was carried out for a spherical nanoparticle with
      polymer chains tethered to its surface. These simulations are relevant to
      understanding the transport properties of polymer-stabilized nanoparticles in
      environmental and other applications. Hydrodynamic interactions (HI) were taken
      into account to properly describe the diffusion properties of a stabilized
      particle. HI are important in this context because of the close proximity of the
      surface-tethered polymer chains. HI were implemented using a method introduced by
      Fixman (1986 Macromolecules 19 1204), which uses a Chebyshev polynomial expansion
      to calculate the square root of the diffusion tensor. Simulation predictions were
      compared to published experimental data for the hydrodynamic radius of a silica
      particle stabilized by polystyrene tethered chains, and good agreement was
      achieved. A relationship that allows polymer-stabilized particles with arbitrary
      polymer-chain densities to be modelled is developed.

PMID- 21727461
TI  - Design of water-soluble, thiol-reactive polymers of controlled molecular weight:
      a novel multivalent scaffold.
AB  - Multivalent molecules, i.e. scaffolds presenting multiple copies of a suitable
      ligand, constitute an emerging class of nanoscale therapeutics. We present a
      novel approach for the design of multivalent ligands, which allows the
      biofunctionalization of polymers with proteins or peptides in a controlled
      orientation. It consists of the synthesis of water-soluble, activated polymer
      scaffolds of controlled molecular weight, which can be biofunctionalized with
      various thiolated ligands in aqueous media under mild conditions. These polymers
      were synthesized by ring-opening metathesis polymerization (ROMP) and further
      modified to make them water-soluble. The incorporation of chloride groups
      activated the polymers to react with thiol-containing peptides or proteins, and
      the formation of multivalent ligands in aqueous media was demonstrated. This
      strategy represents a convenient route for synthesizing multivalent ligands of
      controlled dimensions and valency.

PMID- 21727462
TI  - Layer-by-layer deposition of polyelectrolyte nanolayers on natural fibres:
      cotton.
AB  - The layer-by-layer (LbL) deposition of poly(sodium 4-styrene sulfonate) (PSS) and
      poly(allylamine hydrochloride) (PAH) over cotton fibres is reported. Cotton
      fibres offer unique challenges to the deposition of nanolayers because of their
      unique cross section as well as the chemical heterogeneity of their surface.
      Cationic cotton substrates were produced by using 2,3
      epoxypropyltrimethylammonium chloride. Attenuated total reflectance FTIR, x-ray
      photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) were
      used to validate the presence of the nanolayers as well as to corroborate their
      self-organized structure. TEM images indicated conformal and uniform coating of
      the cotton fibres. XPS spectral data were found to be in quantitative agreement
      with previous published work that studied the LbL deposition of PSS and PAH over
      synthetic substrates.

PMID- 21727463
TI  - Size and distribution prediction for nanoparticles produced by microemulsion
      precipitation: A Monte Carlo simulation study.
AB  - A Monte Carlo simulation approach for BaSO(4) nanoparticle precipitation in
      microemulsions has been applied to a semi-batch reactor experiment. The
      simulation includes two technical process parameters, the feed rate and the
      initial volume ratio of the two reactants. A set of experiments with different
      initial reactant concentrations of BaCl(2) and K(2)SO(4) showed a significant
      change in the particle size. It was compared to the simulated final particle size
      and with an adaptation of one internal parameter of the Monte Carlo simulation a
      good agreement between simulated and experimental data was achieved. Using this
      set of parameters the feed rate and the initial volume ratio is varied. It is
      shown how these process parameters influence the particle size and the size
      distribution. The simulation results may help in finding appropriate control
      parameters in a scale-up approach of the microemulsion technology for
      nanoparticle production.

PMID- 21727464
TI  - Improved metal cluster deposition on a genetically engineered tobacco mosaic
      virus template.
AB  - Improved depositions of various metal clusters onto a biomolecular template were
      achieved using a genetically engineered tobacco mosaic virus (TMV). Wild-type TMV
      was genetically altered to display multiple solid metal binding sites through the
      insertion of two cysteine residues within the amino-terminus of the virus coat
      protein. Gold, silver, and palladium clusters synthesized through in situ
      chemical reductions could be readily deposited onto the genetically modified
      template via the exposed cysteine-derived thiol groups. Metal cluster coatings on
      the cysteine-modified template were more densely deposited and stable than
      similar coatings on the unmodified wild-type template. Combined, these results
      confirm that the introduction of cysteine residues onto the outer surface of the
      TMV coat protein enhances the usefulness of this virus as a biotemplate for the
      deposition of metal clusters.

PMID- 21727465
TI  - Testing the consistency of the Maxwell-Stefan formulation when predicting self
      diffusion in zeolites with strong adsorption sites.
AB  - The Maxwell-Stefan (MS) formulation, as applied to zeolites that contain both
      weak and strong adsorption sites, such as ZSM-5, is compared to dynamic Monte
      Carlo simulations, for the limiting case of single-component self-diffusion. This
      study is intended as a consistency check, and as a step towards an analytical or
      semi-analytical theory for self-diffusion in zeolites with multiple types of
      sites. In its original form, when it is assumed that zeta, the ratio of the self
      exchange coefficient to the corrected diffusivity, is equal to 1, the MS
      formulation performs well for silicalite, the all-Si version of ZSM-5. However,
      when there are lattice heterogeneities or the topology of the pore network
      differs from that of silicalite, it is necessary to assume [Formula: see text].
      Because zeta is generally occupancy dependent, the theory is unsuited as a fully
      predictive theory for self-diffusion in heterogeneous microporous solids, unless
      a theory for zeta is derived. However, since several studies have demonstrated
      that the MS formulation is able to predict multi-component diffusivities from
      single-component diffusivities for zeolites with one type of site, an extension
      to zeolites with multiple types of sites would be very valuable.

PMID- 21727466
TI  - Adhesion of Pseudomonas fluorescens onto nanophase materials.
AB  - Nanobiotechnology is a growing area of research, primarily due to the potentially
      numerous applications of new synthetic nanomaterials in engineering/science.
      Although various definitions have been given for the word 'nanomaterials' by many
      different experts, the commonly accepted one refers to nanomaterials as those
      materials which possess grains, particles, fibres, or other constituent
      components that have one dimension specifically less than 100 nm. In biological
      applications, most of the research to date has focused on the interactions
      between mammalian cells and synthetic nanophase surfaces for the creation of
      better tissue engineering materials. Although mammalian cells have shown a
      definite positive response to nanophase materials, information on bacterial
      interactions with nanophase materials remains elusive. For this reason, this
      study was designed to assess the adhesion of Pseudomonas fluorescens on nanophase
      compared to conventional grain size alumina substrates. Results provide the first
      evidence of increased adhesion of Pseudomonas fluorescens on alumina with
      nanometre compared to conventional grain sizes. To understand more about the
      process, polymer (specifically, poly-lactic-co-glycolic acid or PLGA) casts were
      made of the conventional and nanostructured alumina surfaces. Results showed
      similar increased Pseudomonas fluorescens capture on PLGA casts of nanostructured
      compared to conventional alumina as on the alumina itself. For these reasons, a
      key material property shown to enhance bacterial adhesion was elucidated in this
      study for both polymers and ceramics: nanostructured surface features.

PMID- 21727467
TI  - Engineering nanospaces: ordered mesoporous silicas as model substrates for
      building complex hybrid materials.
AB  - This contribution summarizes investigations of organic-inorganic hybrid materials
      wherein the inorganic phase is ordered mesoporous silica such as MCM-41 and SBA
      15. The review, which covers work performed in the last three years, emphasizes
      studies of: (1) covalently attached functional groups, (2) new approaches to
      functionalization, (3) approaches for achieving high densities of uniform
      functional groups, (4) periodic mesoporous organosilicas (PMOs) with hierarchical
      ordering, (5) new functional chemistries, and (6) the application of new
      materials to enantioselective catalysis and emerging areas. The review concludes
      with the authors outlining some outstanding problems in the field.

PMID- 21727468
TI  - Single-wall carbon nanotube synthesis by CO disproportionation on nickel
      incorporated MCM-41.
AB  - Both Ni- and Co-MCM-41 may be used for the synthesis of single-wall carbon
      nanotubes (SWNT). We present a comparative investigation that demonstrates that
      smaller diameter SWNT with a narrower distribution of diameters are produced
      using Co-MCM-41. Temperature-programmed reduction and x-ray absorption
      spectroscopy were used to measure the reducibility and metal cluster growth of Ni
      and Co-MCM-41 in He, H(2) and under CO disproportionation reaction. The
      differences between these two catalysts can be attributed to a greater
      reducibility of and a greater CO affinity for Ni relative to Co.

PMID- 21727469
TI  - Polymeric worm micelles as nano-carriers for drug delivery.
AB  - Nanoscale carriers of active compounds, especially drugs, need not be spherical
      in shape. Worm micelles as blends of degradable polylactic acid (PLA) and inert
      block copolymer amphiphiles were prepared for controlled release and initial
      study of carrier transport through nano-porous media. The loading capacity of a
      typical hydrophobic drug, Triamterene, and the release of hydrophobic dyes were
      evaluated together with morphological changes of the micelles. Degradation of PLA
      by hydrolysis led to the self-shortening of worms and a clear transition towards
      spherical micelles, correlating with the release of hydrophobic dyes. Perhaps
      equally important for application is the flexibility of worm micelles, which we
      show allows them to penetrate nanoporous gels where 100 nm sized vesicles cannot
      enter. Such gels have served as tissue models, and so the results here
      collectively suggest a new class of hydrophobic drug nano-carriers that are
      capable of tissue permeation as well as controlled release.

PMID- 21727470
TI  - Dendrimer-mediated synthesis of platinum nanoparticles: new insights from
      dialysis and atomic force microscopy measurements.
AB  - In this work, we use AFM measurements in conjunction with dialysis experiments to
      study the synthesis mechanism and physical state of dendrimer-stabilized platinum
      nanoparticles. For characterizing particle size distributions by high resolution
      transmission electron microscopy and AFM, sample preparation by drop evaporation
      presumably minimizes the risk of sample bias that might be found in spin coating
      or dip-and-rinse methods. However, residual synthesis by-products (mainly salts)
      must be removed from solutions of dendrimer-stabilized metal nanoparticles prior
      to AFM imaging. Purification by dialysis is effective for this purpose. We
      discovered, by UV-visible spectrophotometry and atomic absorption (AA)
      spectroscopy, that dialysis using 'regular' cellulose dialysis tubing (12 000 Da
      cut-off) used in all previous work leads to substantial losses of
      poly(amidoamine) (PAMAM) dendrimer (G4OH), PAMAM-Pt(+2) complex, and PAMAM
      stabilized Pt nanoparticles. Use of benzoylated dialysis tubing (1200 Da cut-off)
      shows no losses of G4OH or G4OH-Pt mixtures. We use AFM to see whether selective
      filtration during dialysis introduces sampling bias in the measurement of
      particle size distributions. We compare results (UV-visible spectra, AA results,
      and AFM-based particle size distributions) for a sample of G4OH-Pt(40) divided
      into two parts, one part dialysed with regular dialysis tubing and the other with
      benzoylated tubing. Exhaustive dialysis using benzoylated tubing may lead to the
      loss of colloidal Pt nanoparticles stabilized by adsorbed dendrimer, but not Pt
      nanoparticles encapsulated by the dendrimer. The comparisons also lead to new
      insights concerning the underlying synthesis mechanisms for PAMAM-stabilized Pt
      nanoparticles.

PMID- 21727471
TI  - Large- and small-nanopore silica prepared with a short-chain cationic fluorinated
      surfactant.
AB  - A cationic partially fluorinated surfactant with four carbons in the chain 1
      (3,3,4,4,4-pentafluorobutyl)pyridinium chloride is employed as a structure
      directing agent to synthesize nanoporous silica. Samples are prepared in dilute
      ammonia solutions at room temperature with a range of surfactant:Si ratios. The
      sample with the largest surfactant:Si ratio forms particles with wormhole-like
      micropores with an average diameter of 1.6 nm, which corresponds to the
      anticipated small size of the surfactant aggregates. On the other hand, the
      sample with the smallest surfactant:Si ratio forms a gel that, upon drying, has
      uniform 11.1 nm pores. The formation and stabilization of the latter large
      mesopore structure is unusual for a sample prepared and dried under ambient
      conditions, and may reflect favourable roles of the surfactant both in inducing
      gelation and in stabilizing the pore structure during drying.

PMID- 21727472
TI  - Structure and melt rheology of polystyrene-based layered silicate nanocomposites.
AB  - The melt-state viscoelastic properties of exfoliated in situ polymerized and
      intercalated solution-blended polystyrene (PS) and organically modified
      montmorillonite nanocomposites were investigated and compared. The PS
      nanocomposites prepared by nitroxide-mediated polymerization (NMP) exhibit a
      stable exfoliated structure whereas the PS nanocomposites prepared by solution
      mixing exhibit an intercalated structure. The linear viscoelastic properties were
      strongly correlated with the dispersion state of the nanocomposites. On the other
      hand, the non-linear oscillatory shear properties exhibited shear thinning
      character and were consistent with the weak interactions between the polymer and
      the layered silicate.

PMID- 21727473
TI  - Diffusion of water and sodium counter-ions in nanopores of a beta-lactoglobulin
      crystal: a molecular dynamics study.
AB  - The dynamics of water and sodium counter-ions (Na(+)) in a C222(1) orthorhombic
      beta-lactoglobulin crystal is investigated by means of 5 ns molecular dynamics
      simulations. The effect of the fluctuation of the protein atoms on the motion of
      water and sodium ions is studied by comparing simulations in a rigid and in a
      flexible lattice. The electrostatic interactions of sodium ions with the
      positively charged LYS residues inside the crystal channels significantly
      influence the ionic motion. According to our results, water molecules close to
      the protein surface undergo an anomalous diffusive motion. On the other hand, the
      motion of water molecules further away from the protein surface is normal
      diffusive. Protein fluctuations affect the diffusion constant of water, which
      increases from 0.646 +/- 0.108 to 0.887 +/- 0.41 nm(2) ns(-1), when protein
      fluctuations are taken into account. The pore size (0.63-1.05 nm) and the water
      diffusivities are in good agreement with previous experimental results. The
      dynamics of sodium ions is disordered. LYS residues inside the pore are the main
      obstacles to the motion of sodium ions. However, the simulation time is still too
      short for providing a precise description of anomalous diffusion of sodium ions.
      The results are not only of interest for studying ion and water transport through
      biological nanopores, but may also elucidate water-protein and ion-protein
      interactions in protein crystals.

PMID- 21727474
TI  - Rheological behaviour and mechanical characterization of injectable
      poly(propylene fumarate)/single-walled carbon nanotube composites for bone tissue
      engineering.
AB  - This work investigated the effects of the use of a surfactant or the
      functionalization of single-walled carbon nanotubes (SWNTs) on their dispersion
      in uncrosslinked poly(propylene fumarate) (PPF) and the mechanical reinforcement
      of crosslinked composites as a function of the SWNT concentration. Rheological
      measurements showed good dispersion of SWNTs in uncrosslinked PPF at low
      concentrations of 0.05 wt% and SWNT aggregation for higher concentrations for all
      formulations examined. Mechanical testing demonstrated significant reinforcement
      in the compressive and flexural mechanical properties of crosslinked
      nanocomposites which peaked for low SWNT concentrations of the order of 0.05 wt%.
      For example, a 74% increase was recorded for the compressive modulus and a 69%
      increase for the flexural modulus of nanocomposites with functionalized SWNTs at
      a 0.05 wt% loading. Nevertheless, this reinforcement was not related to the use
      of a surfactant or the functionalization of the SWNTs tested. Scanning electron
      microscopy examinations of fractured nanocomposite surfaces revealed the
      formation of SWNT aggregates at higher concentrations corroborating the
      rheological and mechanical data. These results suggest that the dispersion of
      individual SWNTs in a uncrosslinked formulation is pivotal to the development of
      injectable nanocomposites for bone tissue engineering applications.

PMID- 21727475
TI  - Cutting single-walled carbon nanotubes.
AB  - A two-step process is utilized for cutting single-walled carbon nanotubes
      (SWNTs). The first step requires the breakage of carbon-carbon bonds in the
      lattice while the second step is aimed at etching at these damage sites to create
      short, cut nanotubes. To achieve monodisperse lengths from any cutting strategy
      requires control of both steps. Room-temperature piranha and ammonium persulfate
      solutions have shown the ability to exploit the damage sites and etch SWNTs in a
      controlled manner. Despite the aggressive nature of these oxidizing solutions,
      the etch rate for SWNTs is relatively slow and almost no new sidewall damage is
      introduced. Carbon-carbon bond breakage can be introduced through fluorination to
      ~C(2)F, and subsequent etching using piranha solutions has been shown to be very
      effective in cutting nanotubes. The final average length of the nanotubes is
      approximately 100 nm with carbon yields as high as 70-80%.

PMID- 21727476
TI  - Effect of interfacial reaction rate on the morphogenesis of nanostructured
      coatings in a simulated electrodeposition process.
AB  - Brownian dynamics simulations (BDSs) are performed to investigate the influence
      of interfacial electrochemical reaction rate on the evolution of coating
      morphology on circular fibres. The boundary condition for the fluid phase
      concentration, representing the balance between the rates of interfacial reaction
      and transport of ions by bulk diffusion, is incorporated into the BDS by using a
      reaction probability, P(s). Different modes of growth, ranging from diffusion
      limited ([Formula: see text]) to reaction controlled [Formula: see text], are
      studied. It is found that, consistent with experimental observations, two
      distinct morphological regimes exist, with a dense and uniform structure for
      [Formula: see text] (reaction limited deposition (RLD)) and an open and porous
      one as [Formula: see text] (diffusion limited deposition (DLD)). An analysis of
      the fractal dimension indicates that this morphological transition occurs at
      P(s)~0.3. Long-time power-law scalings for the evolution of thickness [Formula:
      see text] and roughness (xi) of the coating exist, i.e. [Formula: see text] with
      0.86<=alpha<=0.91 and 0.56<=beta<=0.93 for 0.01<=P(s)<=1. These values are
      different from those reported for sequential, pseudo-time lattice simulations on
      planar surfaces, signifying the importance of multiparticle dynamics and surface
      curvature. The internal structure and porosity of the coating are characterized
      quantitatively by the radial density profile, pair correlation function, two
      point probability function, void distribution function and pore area
      distribution. For RLD the radial density, rho(n), remains nearly constant, while
      for DLD rho(n) follows a power law, [Formula: see text]. The coating exhibits
      short ranged order in the RLD regime while a long range order is created by DLD.
      The void distribution function becomes broader with increasing P(s), indicating
      that in the RLD regime the coating consists of small and spherical pores, while
      in the DLD regime large and elongated pores are obtained. The pore area
      distribution shows narrower distributions in DLD for small pores, while the area
      of the largest pore increases by nearly three orders of magnitude as one moves
      from the RLD to the DLD regime. Such morphological diversity could be potentially
      exploited for applications such as percolation, catalysis and surface protection.

PMID- 21727477
TI  - Synthesis of magnetic nanocomposites and alloys from platinum-iron oxide core
      shell nanoparticles.
AB  - This paper presents a systematic study on the generation of iron platinum
      containing magnetic nanocomposites and alloys from Pt@Fe(2)O(3) core-shell
      nanoparticle precursors. These core-shell nanoparticles were made using a
      sequential synthetic approach. They could form FePt alloys and alloy-containing
      nanocomposites through a solid-state reaction at >400  degrees C. The chemical
      compositions of FePt alloys were controllable by using Pt@Fe(2)O(3) core-shell
      nanoparticles that had the designed Pt core diameter and iron oxide shell
      thickness. We show that face-centred tetragonal (fct) FePt@Fe core-shell
      nanoparticles could be made from Pt@Fe(2)O(3) core-shell nanoparticles with 5%
      hydrogen in argon (v/v). Furthermore, various FePt alloys and alloy-containing
      nanocomposites including metastable intermediate phases could be obtained. The
      materials were characterized by high resolution scanning transmission electron
      microscopy (HR-STEM), energy dispersive x-ray (EDX) spectroscopy, powder x-ray
      diffraction (PXRD), parallel electron energy loss spectroscopy (PEELS), and
      superconducting quantum interference device (SQUID) magnetometry. These materials
      could have potential applications as permanent hard magnets and data storage
      media.

PMID- 21727478
TI  - Predictive control of crystal size distribution in protein crystallization.
AB  - This work focuses on the modelling, simulation and control of a batch protein
      crystallization process that is used to produce the crystals of tetragonal hen
      egg-white (HEW) lysozyme. First, a model is presented that describes the
      formation of protein crystals via nucleation and growth. Existing experimental
      data are used to develop empirical models of the nucleation and growth mechanisms
      of the tetragonal HEW lysozyme crystal. The developed growth and nucleation rate
      expressions are used within a population balance model to simulate the batch
      crystallization process. Then, model reduction techniques are used to derive a
      reduced-order moments model for the purpose of controller design. Online
      measurements of the solute concentration and reactor temperature are assumed to
      be available, and a Luenberger-type observer is used to estimate the moments of
      the crystal size distribution based on the available measurements. A predictive
      controller, which uses the available state estimates, is designed to achieve the
      objective of maximizing the volume-averaged crystal size while respecting
      constraints on the manipulated input variables (which reflect physical
      limitations of control actuators) and on the process state variables (which
      reflect performance considerations). Simulation results demonstrate that the
      proposed predictive controller is able to increase the volume-averaged crystal
      size by 30% and 8.5% compared to constant temperature control (CTC) and constant
      supersaturation control (CSC) strategies, respectively, while reducing the number
      of fine crystals produced. Furthermore, a comparison of the crystal size
      distributions (CSDs) indicates that the product achieved by the proposed
      predictive control strategy has larger total volume and lower polydispersity
      compared to the CTC and CSC strategies. Finally, the robustness of the proposed
      method (achieved due to the presence of feedback) with respect to plant-model
      mismatch is demonstrated. The proposed method is demonstrated to successfully
      achieve the task of maximizing the volume-averaged crystal size in the presence
      of plant-model mismatch, and is found to be robust in comparison to open-loop
      optimal control strategies.

PMID- 21727479
TI  - Understanding catalysed growth of single-wall carbon nanotubes.
AB  - Classical molecular dynamics simulations using a reactive force field, which
      allows simulation of bond-breaking and bond-forming, are carried out to
      investigate the several stages of a catalysed synthesis process of single-wall
      carbon nanotubes. The simulations assume instantaneous catalysis of a precursor
      gas on the surface of metallic nanoclusters, illustrating how carbon atoms
      dissolve in the metal cluster and then precipitate on its surface, evolving into
      various carbon structures, finally forming a cap which eventually grows to a
      single-wall nanotube. The results are discussed in the context of experimental
      synthesis results.

PMID- 21727480
TI  - The nature of 'overexchanged' copper and platinum on zeolites.
AB  - The uptake of platinum and copper tetra-ammine (PTA and CTA, [(NH(3))(4)Pt](2+)
      and [(NH(3))(4)Cu](2+)) into zeolites was compared over silica and three zeolites
      (Y, MOR and MFI) with different points of zero charge and aluminium content.
      Adsorption was determined as a function of pH at several metal concentrations,
      and pH shifts relative to metal free control experiments were carefully
      monitored. The uptake of both metal ammine complexes onto silica is well
      described by electrostatic adsorption. We suggest that the metal cations interact
      with zeolites by two mechanisms, ion exchange at the Al exchange sites and
      electrostatic adsorption at silanol groups. The former is the dominant mechanism
      at low to mid pH, and the latter at high pH. This effect is most clearly
      manifested in zeolites with low aluminium content such as ZSM5; electrostatic
      adsorption at high pH in ZSM5 yields metal loadings much in excess of the ion
      exchange capacity and so gives rise to 'overexchange'. Differences between PTA
      and CTA can be explained by the weaker stability of the CTA complex and its
      response to the decrease in local pH near the adsorption plane of low PZC
      zeolites. This change in local pH near oxide surfaces is characteristic of
      electrostatic adsorption. As the local pH decreases, the CTA ion is probably
      converted to a dimerized copper complex, perhaps Cu(2)(OH)(2)(2+). A portion of
      the released ammonia is protonated, increasing the solution pH. In high PZC, high
      aluminium zeolites with high ion exchange capacity, there is relatively little
      contribution from electrostatic adsorption.

PMID- 21727481
TI  - Silver carboxylate nanostructure nucleation and growth on AgBr crystals.
AB  - The initial stage of the reaction between sodium stearate (NaSt) and AgNO(3)
      produces silver stearate (AgSt) micelles, [(C(18)H(35)O(2))(x)(Na(x
      y))(Ag(y))(H(2)O)(z)], and aggregations of these AgSt micelles in the form of
      cubic pre-AgSt crystals. When cubic grains of 50 nm AgBr are added to the NaSt
      dispersion prior to the AgNO(3), the reaction proceeds to form the silver
      stearate micelles, but not the aggregation of those micelles. Instead, the {111}
      silver ion planes of the cubic AgBr crystal corners provide nucleation sites for
      silver stearate micelle deposition and crystal growth. After nucleation, the AgSt
      micelles evolve into nanostructured bud-like formations via an epitaxial
      interface on one or several corners of each AgBr cubic crystal. Over time,
      additional AgSt micelle deposition enables the buds to grow longer into strand
      like structures, which then connect to form the beginnings of the ultimate silver
      stearate crystal plates.

PMID- 21727482
TI  - Increased osteoblast functions on nanophase titania dispersed in poly-lactic-co
      glycolic acid composites.
AB  - The design of nanophase titania/poly-lactic-co-glycolic acid (PLGA) composites
      offers an exciting approach to combine the advantages of a degradable polymer
      with nano-size ceramic grains to optimize physical and biological properties for
      bone regeneration. Importantly, nanophase titania mimics the size scale of
      constituent components of bone since it is a nanostructured composite composed of
      nanometre dimensioned hydroxyapatite well dispersed in a mostly collagen matrix.
      For these reasons, the objective of the present in vitro study was to investigate
      osteoblast (bone-forming cell) adhesion and long-term functions on nanophase
      titania/PLGA composites. Since nanophase titania tended to significantly
      agglomerate when added to polymers, different sonication output powers were
      applied in this study to improve titania dispersion. Results demonstrated that
      the dispersion of titania in PLGA was enhanced by increasing the intensity of
      sonication and that greater osteoblast adhesion correlated with improved
      nanophase titania dispersion in PLGA. Moreover, results correlated better
      osteoblast long-term functions, such as alkaline phosphatase activity and calcium
      containing mineral deposition, on nanophase titania/PLGA composites compared to
      plain PLGA. In fact, the greatest collagen production by osteoblasts occurred
      when cultured on nanophase titania sonicated in PLGA at the highest powers. In
      this manner, the present study demonstrates that PLGA composites with well
      dispersed nanophase titania can enhance osteoblast functions necessary for
      improved bone tissue engineering applications.

PMID- 21727483
TI  - Morphology and composition of spray-flame-made yttria-stabilized zirconia
      nanoparticles.
AB  - Homogeneous yttria-stabilized zirconia (YSZ) with 8-31 nm average crystallite and
      particle diameter containing 3-10 mol% yttria are made by flame spray pyrolysis
      (FSP) of various yttrium and zirconium precursors at production rates up to 350 g
      h(-1). Product particles are characterized by N(2) adsorption (BET), transmission
      electron microscopy (TEM), energy-dispersive x-ray spectroscopy (EDS) and x-ray
      diffraction (XRD). The effect of liquid precursor composition on product particle
      morphology, composition and crystallinity is investigated. The yttria content
      does not affect the product primary particle and crystal sizes of homogeneous
      YSZ. These are determined, in turn, by the process enthalpy content and overall
      metal concentration. Flame-made YSZ nanoparticles of homogeneous composition and
      morphology are formed when using either only organometallic zirconium and yttrium
      precursors or 2-ethylhexanoic acid as solvent and inexpensive zirconium carbonate
      and yttrium nitrate hexahydrate as precursors. In contrast, and consistent with
      the literature, hollow or inhomogeneous YSZ particles are made when
      organometallic zirconium and yttrium nitrate precursors of high water content are
      employed, especially at high production rate. The ratio of XRD-determined small
      to large sizes for inhomogeneous crystalline particles is an effective
      quantitative measure of their degree of inhomogeneity. For such inhomogeneous
      particles nitrogen adsorption is not a reliable technique for the average grain
      size as it relies on integral properties of the particle size distribution.

PMID- 21727484
TI  - Synthesis and agglomeration of gold nanoparticles in reverse micelles.
AB  - Reverse micelles prepared in the system water, sodium bis-(2-ethylhexyl)
      sulfoccinate (AOT), and isooctane were investigated as a templating system for
      the production of gold nanoparticles from Au(III) and the reducing agent sulfite.
      A core-shell Mie model was used to describe the optical properties of gold
      nanoparticles in the reverse micelles. Dynamic light scattering of gold colloids
      in aqueous media and in reverse micelle solution indicated agglomeration of
      micelles containing particles. This was verified theoretically with an analysis
      of the total interaction energy between pairs of particles as a function of
      particle size. The analysis indicated that particles larger than about 8 nm in
      diameter should reversibly flocculate. Transmission electron microscopy
      measurements of gold nanoparticles produced in our reverse micelles showed
      diameters of 8-10 nm. Evidence of cluster formation was also observed. Time
      correlated UV-vis absorption measurements showed a red shift for the peak
      wavelength. This was interpreted as the result of multiple scattering and plasmon
      interaction between particles due to agglomeration of micelles with particles
      larger than 8 nm.

PMID- 21727485
TI  - Molecular dynamics simulations of the straining of nanoparticle chain aggregates:
      the case of copper.
AB  - Previous studies in our laboratory have shown that individual nanoparticle chain
      aggregates (NCAs) exhibit unusual mechanical behaviour when under strain inside
      the transmission electron microscope. NCAs made of various materials (e.g.
      carbon, metal oxides and metals) were strained by as much as 100% under tension.
      The nanoparticles that compose the chains were 5-10 nm in diameter and the chains
      of the order of 1 um in length. Such aggregates are of technological importance
      in the manufacture of nanocomposite materials (e.g. rubber), aggregate break-up
      (e.g. sampling diesel emissions) and chemical-mechanical planarization. The goal
      of this study was to simulate the mechanical behaviour of chain aggregates with
      morphological properties similar to those of technological interest. Molecular
      dynamics (MD) and energy minimization computer simulations are employed to
      investigate, at the atomic scale, the behaviour of short nanoparticle aggregates
      under strain and to obtain quantitative information on the forces involved in
      aggregate straining and fracturing. The interaction potential used is that of
      copper obtained with the embedded atom method (EAM). Two seven-nanoparticle
      aggregates are studied, one linear and the other kinked. The seven nanoparticles
      in both aggregates are single crystals and about 2.5 nm in diameter each. The
      aggregates are strained along their longest dimension, to the breaking point, at
      strain rates spanning from 2.5 * 10(7) to 8.0 * 10(8) s(-1) (MD simulations). The
      linear aggregate yield strain is about 0.1. The kinked aggregate elastic limit is
      also about 0.1, but only one-third of the stress develops along the straining
      direction compared to the linear aggregate. The kinked aggregate breaks at a
      strain of about 0.5, five times higher than the breaking strain of the linear
      aggregate. The ability of the kinked aggregate to straighten through combined
      nanoparticle interface sliding and rotation accounts for the extra strain
      accommodation. Simulation strain rates are orders of magnitude higher than the
      experimental ones. However, aggregate behaviour is independent of strain rates
      over the range studied here. The MD and energy minimization straining gave very
      similar results. In the elastic regime, the 1/S(11) modulus for the seven
      nanoparticle kinked aggregate is about one-fifth of the bulk value. This is due
      to a combined effect of the small primary particle diameter and the aggregate
      kinked structure. If this softening behaviour also occurs for nanoparticle
      aggregates of other materials (e.g. carbon, silica), nanoparticle aggregates, in
      some cases, may be strained along with the nanocomposite they reinforce.

PMID- 21727486
TI  - Au and NiO nanocrystals doped into porous sol-gel SiO(2) films and the effect on
      optical CO detection.
AB  - Thin-film composites comprised of NiO and NiO/Au nanoparticles in a porous SiO(2)
      matrix have been prepared using the sol-gel technique. When at elevated
      temperatures (200  degrees C< T<350  degrees C) and exposed to carbon monoxide,
      the films undergo reversible changes in optical transmittance at wavelengths in
      the visible-near IR region. For NiO composite films heated at 330  degrees C and
      exposed to 1% CO in air, there is an increase in transmittance which approaches 2
      4% over most of the visible range. For NiO/Au composite films the transmittance
      increase exhibits a wavelength dependence, with a maximum change which is close
      to 6% at lambda~630 nm and which is close to zero in the Au plasmon resonance
      range (lambda~550 nm).

PMID- 21727487
TI  - Pick-and-place nanomanipulation using microfabricated grippers.
AB  - Microfabricated grippers could be useful for the manipulation of nanoscopic and
      microscopic samples. A survey is presented of the force requirements for a
      microgripper to complete pick-and-place nanomanipulation tasks. We then
      demonstrate in situ pick-and-place operations of nanowires inside a scanning
      electron microscope using microfabricated electrostatically actuated grippers,
      and compare the theoretically estimated force requirements with the results of
      experimental tests of picking up nanowires to evaluate how grippers and
      strategies for nanomanipulation can be optimized.

PMID- 21727488
TI  - Effects of fill fraction on the capture efficiency of nanoscale molecular
      transducers.
AB  - We study the effects of nanotransducer fill fraction on the molecular capture
      efficiency contribution to overall sensor response. Contrary to expectation, we
      show that the relative capture efficiency can exceed the fill fraction in the
      transient regime. However, at thermodynamic equilibrium, the relative efficiency
      equals the fill fraction in the probe-limited case. When the number of target
      molecules in solution is the limiting factor in capture, then gains in capture
      efficiency can be obtained even at thermodynamic equilibrium. The important
      implication of these results is that significant intrinsic nanotransducer
      enhancement is necessary in order to provide net gain in sensor response, but
      that nanotransducer enhancement does not need to exceed the inverse fill
      fraction. In addition, net gain in overall sensor response is more readily
      achievable at low target concentrations.

PMID- 21727489
TI  - Cell adhesion and related phenomena on the surface-modified Au-deposited nerve
      microelectrode examined by total impedance measurement and cell detachment tests.
AB  - This study investigated alkanethiolate self-assembled monolayers (SAMs) of varied
      chain lengths adsorbed upon novel Au-coated microelectrodes, of which the surface
      properties were quantitatively evaluated by surface characterization and 3T3
      fibroblast cell adhesion, total impedance and cell detachment tests. Thin-film
      SAMs adsorbed upon Au/PI/Si provided a hydrophobic or passive surface with
      increased water contact angle and initial total impedance. From cell adhesion
      tests, we can observe that the film formed as a dense-packed spacer resulted in
      incomplete cell sealing of 3T3 cells upon the surface-modified microelectrode.
      Thus the decrease in cell coverage rate and in the slope in association with
      total impedance as a function of cell-surface reaction time can be found. To
      study the adhesion force of a comparable single cell attached upon varied
      modified surfaces, a cell detachment test using a triangular probe tip of a well
      defined cantilever was carried out in medium containing fibroblast cells.
      Overall, both the peak force and the work required to detach a comparable single
      cell from the anchoring domain corresponded well to the increased length of alkyl
      chains adsorbed upon Au/PI/Si. Both measurements on the SAM modified surfaces
      demonstrated much smaller values than those on the pristine Au/PI/Si surface.
      These results concluded that a cell-repulsive characteristic was clearly formed
      on the SAM modified microelectrode surface. The non-adhering properties of
      surface-modified microelectrodes should provide better sensitivity for
      neuromuscular stimulation as well as for the recording of infinitesimal neural
      signals in future applications of neural prostheses.

PMID- 21727490
TI  - Synthesis and characterization of water-soluble multiwalled carbon nanotubes
      grafted by a thermoresponsive polymer.
AB  - Water-soluble multiwalled carbon nanotubes (MWNTs) with temperature-responsive
      shells were successfully prepared by grafting poly (N-isopropylacrylamide)
      (PNIPAM) from the sidewalls of MWNTs, via surface reversible addition
      fragmentation chain transfer (RAFT) polymerization using RAFT agent
      functionalized MWNTs as the chain transfer agent. Thermogravimetric analysis
      (TGA) measurements showed that the weight composition of the as-grown PNIPAM
      polymers on the MWNTs can be well controlled by the feed ratio (in weight) of
      NIPAM to RAFT agent functionalized MWNTs (MWNT-SC(S)Ph). The MWNT-g-PNIPAM has
      good solubility in water, chloroform, and tetrahydrofuran (THF). Transmission
      electron microscope (TEM) and scanning electron microscope (SEM) images also
      showed that the MWNT-g-PNIPAM was dispersed individually and eventually bonded
      with the polymer layer by surface RAFT polymerization. The PNIPAM shell is very
      sensitive to a change of temperature. This method could find potential
      applications by grafting other functional polymer chains onto MWNTs.

PMID- 21727491
TI  - Defect tolerance in resistor-logic demultiplexers for nanoelectronics.
AB  - Since defect rates are expected to be high in nanocircuitry, we analyse the
      performance of resistor-based demultiplexers in the presence of defects. The
      defects observed to occur in fabricated nanoscale crossbars are stuck-open, stuck
      closed, stuck-short, broken-wire, and adjacent-wire-short defects. We analyse the
      distribution of voltages on the nanowire output lines of a resistor-logic
      demultiplexer, based on an arbitrary constant-weight code, when defects occur.
      These analyses show that resistor-logic demultiplexers can tolerate small numbers
      of stuck-closed, stuck-open, and broken-wire defects on individual nanowires, at
      the cost of some degradation in the circuit's worst-case voltage margin. For
      stuck-short and adjacent-wire-short defects, and for nanowires with too many
      defects of the other types, the demultiplexer can still achieve error-free
      performance, but with a smaller set of output lines. This design thus has two
      layers of defect tolerance: the coding layer improves the yield of usable output
      lines, and an avoidance layer guarantees that error-free performance is achieved.

PMID- 21727492
TI  - Concept of nonvolatile memory based on multiwall carbon nanotubes.
AB  - In this study, a novel concept is proposed for molecular electronics that uses
      vertically aligned multiwall carbon nanotubes as nonvolatile memory elements.
      Nanotubes grown on a patterned substrate may be opened by partially deleting the
      outer molecular layer or layers, so that the inner core is able to move along the
      vertical tube axis. Mounting another dielectric plate above the nanotube forest
      at a specific distance from the tube caps can provide two stable van der Waals
      states of the inner core, providing for nonvolatile data storage. A device built
      using this architecture can function as a two-dimensional memory array. At each
      cross point in the array, a multiwall carbon nanotube exists in either the
      separated off-state or in the contact on-state, and can be switched between these
      states by applying voltage pulses at the corresponding electrodes. A theoretical
      memory density as high as 10(13) memory elements per square centimetre is
      possible, with an operation frequency exceeding 100 GHz. Significant physical
      characteristics of such a device are bi-stability and reversibility. Such a
      device can function both as nonvolatile random access memory and as terabit solid
      state storage.

PMID- 21727493
TI  - Growth of multi-amine terminated poly(amidoamine) dendrimers on the surface of
      carbon nanotubes.
AB  - An in situ repetitive divergent polymerization strategy was employed to grow
      multi-amine poly(amidoamine) dendritic macromolecules on the surfaces of
      multiwalled carbon nanotubes (MWNTs), affording novel three-dimensional (3D)
      molecular nanocomposites. The crude MWNTs were oxidized using H(2)SO(4)/HNO(3) =
      3:1 (v/v) and then reacted with thionyl chloride, resulting in MWNTs
      functionalized with chlorocarbonyl groups (MWNT-COCl). MWNT-COCl, when reacted
      with an excess of ethylenediamine, produced amine-functionalized MWNT supported
      initiators (MWNT-NH(2)). Using the MWNT-NH(2) as the growth supporter and
      methylacrylate/ethylenediamine as building blocks, multi-amine dendritic
      poly(amidoamine) macromolecules were covalently grafted onto the sidewalls and
      ends of MWNTs via Michael addition reaction and amidation. Thermal gravimetric
      analysis (TGA) measurements showed that the weight ratio of the as-grown
      dendritic polymers on the MWNT surfaces lay in the 10%-50% range. The products
      were also characterized by Fourier transform infrared (FTIR), Raman, nuclear
      magnetic resonance (NMR), and transmission electron microscopy (TEM) analysis.
      The results indicate that the dendrimers are grafted onto the surface of MWNTs.
      The as-prepared nanocomposites exhibit excellent dispersibility in water.

PMID- 21727494
TI  - Visible-light-responsive nano-TiO(2) with mixed crystal lattice and its
      photocatalytic activity.
AB  - Ultraviolet- and visible-light-responsive titania-based photocatalysts were
      synthesized and employed in the photocatalytic oxidation of NO(x). Sol-gel
      processes using tetrabutyl orthotitanate and ethanol under acid catalyzed
      condition and controlled calcination were performed to synthesize titanium
      dioxide with a mixed crystal lattice of anatase, brookite and rutile phases. The
      TiO(2) prepared under calcination at 200  degrees C exhibited high photocatalytic
      activity for degradation of NO(x) under both ultraviolet (UV) and visible-light
      illumination. The experimental results showed that up to 70% removal of NO(x)
      could be obtained in a continuous flow type reaction system under irradiation
      with visible light. The calcination temperature has an important influence on the
      particle size and lattice structure of TiO(2). It is also found that the peculiar
      mixed-phase structure of TiO(2), evidenced from Raman, x-ray diffractometry
      (XRD), and UV-vis spectroscopy, was inferred to be an important factor for
      visible-light absorption and NO(x) removal activity under a wide range of visible
      light illumination.

PMID- 21727495
TI  - Design and fabrication of nanofluidic devices by surface micromachining.
AB  - Using surface micromachining technology, we fabricated nanofluidic devices with
      channels down to 10 nm deep, 200 nm wide and up to 8 cm long. We demonstrated
      that different materials, such as silicon nitride, polysilicon and silicon
      dioxide, combined with variations of the fabrication procedure, could be used to
      make channels both on silicon and glass substrates. Critical channel design
      parameters were also examined. With the channels as the basis, we integrated
      equivalent elements which are found on micro total analysis (MUTAS) chips for
      electrokinetic separations. On-chip platinum electrodes enabled electrokinetic
      liquid actuation. Micro-moulded polydimethylsiloxane (PDMS) structures bonded to
      the devices served as liquid reservoirs for buffers and sample. Ionic conductance
      measurements showed Ohmic behaviour at ion concentrations above 10 mM, and
      surface charge governed ion transport below 5 mM. Low device to device
      conductance variation (1%) indicated excellent channel uniformity on the wafer
      level. As proof of concept, we demonstrated electrokinetic injections using an
      injection cross with volume below 50 attolitres (10(-18) l).

PMID- 21727496
TI  - Plasmon resonances of gold nanoparticles incorporated inside an optical fibre
      matrix.
AB  - Metallic nanoparticles were incorporated into the core of standard
      telecommunication grade optical fibres. This creates a simple, yet robust,
      platform which can be used to investigate the properties of nanoparticles, for
      sensing, spectroscopy, and optical switching applications. The optical response
      of gold nanoparticles embedded in the optical fibre matrix was evaluated as a
      function of temperature and the use of the structure as an inline fibre-optic
      temperature sensor is described. A redshift in the localized surface plasmon
      (LSP) resonance related peak, as well as broadening of the plasmon resonance, was
      observed upon increasing the temperature of the nanoparticle containing fibre.
      The shift and broadening of the plasmon resonance were attributed to the
      temperature dependence of dielectric constants of metallic nanoparticles and the
      silica matrix and to plasmon-phonon interactions.

PMID- 21727497
TI  - Magnetically assembled 30 nm diameter nickel nanowire with ferromagnetic
      electrodes.
AB  - Facile, cost-effective, and manufacturable techniques to create single-nanowire
      based devices with good electrical interconnects is demonstrated by combining
      template directed electrodeposition, magnetic assembly, and a post-annealing in a
      reducing environment. Nickel nanowires with a diameter of approximately 30 nm
      were electrodeposited from low-stress nickel sulfamate baths at room temperature
      using in-house made anodized alumina as a nanotemplate. After electrodeposition,
      nanowires were released from the template, efficiently positioned, trapped, and
      assembled on ferromagnetic electrodes using the magnetic interaction between the
      nanowires and the electrodes. By annealing the interconnect in a reducing
      environment of 5%H(2)+95%N(2) at 300  degrees C for 30 min, the interconnect's
      resistance was dramatically reduced from >10 M Omega to 835 Omega.
      Magnetotransport studies at 300 K on a single nickel interconnect with diameters
      ranging from 30 to 200 nm show a strong diameter dependent magnetoresistance,
      which might be attributed to different domain structure within the interconnect.

PMID- 21727498
TI  - Swift heavy ion induced formation of nanocolumns of C clusters in a Si based
      polymer.
AB  - The formation of nanocolumns of C clusters in thin films of a Si based inorganic
      polymer, allylhydridopolycarbosilane (HPCS), as a result of irradiation of the
      films with 100 MeV Au ions at fluences of 2 * 10(12) and 5 * 10(12) ions cm(-2)
      is demonstrated. The evolution and arrangement of the C clusters while subjected
      to the irradiation fluence is investigated by energy filtered cross-sectional
      transmission electron microscopy. Irradiation results in evolution of C clusters
      of sizes <=5 nm, and their alignment along channels of ~10 nm diameter, which are
      essentially the latent tracks created by the Au ions in the polymer. At the
      fluence of 5 * 10(12) ions cm(-2), these clusters become densely packed in the
      channels. The growth of such C cluster filled nanocolumns is shown to be a
      consequence of two simultaneous diffusion processes taking place during the
      transient molten phase of the latent tracks.

PMID- 21727499
TI  - Effect of nanoparticles on sessile droplet contact angle.
AB  - This paper investigates the change in contact angle of droplets of fluid
      containing dispersed nanoparticles (nanofluid) functionalized with thioglycolic
      acid molecules as a function of the concentration and size of nanoparticles, and
      the quality and composition of the substrate material. Bismuth telluride
      nanoparticles with an average size ranging from 2.5 to 10.4 nm and functionalized
      with thioglycolic acid groups were grown by a microemulsion method and dispersed
      in water. Experimental measurements of the contact angle of nanofluid droplets
      cast on smooth glass and silicon substrates show that the contact angle depends
      strongly on nanoparticle concentration. Moreover, smaller size nanoparticles lead
      to larger changes in contact angle at the same mass concentration. These findings
      contribute to understanding the role of functionalized nanoparticles in surface
      wettability.

PMID- 21727500
TI  - Co(3)O(4) nanoparticles produced by mechanochemical reactions.
AB  - Co(3)O(4) nanoparticles have been produced by mechanochemical reactions involving
      cobalt carbonate, sodium oxide and sodium carbonate. The mechanochemical
      reactions are carried out during milling at room temperature and the
      nanoparticles have been obtained without the need for any thermal treatment after
      the milling operation. The CoO phase is produced in the first 30 min of the
      mechanochemical process, followed by a second stage of oxidation to Co(3)O(4)
      which lasts for several hours. Under proper milling conditions the final products
      were soft agglomerates of ultrafine particles with average sizes between 15 and
      20 nm.

PMID- 21727501
TI  - Nanostructure patterns of piezoelectric and ferroelectric complex oxides with
      various shapes, obtained by natural lithography and pulsed laser deposition.
AB  - A variety of patterns of well-ordered perovskite-type complex oxide
      nanostructures were obtained by pulsed laser deposition (PLD) on conductive
      single crystalline substrates through latex sphere monolayer and double-layer
      masks. Patterns obtained via deposition through hexagonally close packed (hcp)
      latex sphere monolayers include the usual arrays of hexagonally ordered
      nanoislands, hexagonal arrays of nanorings of much lower height coexisting with
      hexagonal nanoislands, hcp shell-like structures, and hexagonally interconnected
      nanocrown arrays. The formation of the nanopatterns depends on the ambient gas
      pressure during PLD, with well-separated nanoislands obtained at low pressures,
      and interconnected nanocrowns formed at high pressures. After annealing, the
      obtained BaTiO(3) and SrBi(2)Ta(2)O(9) nanopatterns were examined by
      piezoresponse force microscopy using conductive scanning probes. Under an
      external biasing electric field, polarization domain reversal was observed in the
      nanopatterns with deep submicron lateral dimensions. BaTiO(3) nanocrowns ~9 nm
      high are ferroelectric, while SrBi(2)Ta(2)O(9) nanorings of ~5 nm thickness show
      at least piezoelectric activity. In addition to the patterns of hexagonally
      ordered nanostructure arrays, a pattern of rhombohedrally ordered nanostructure
      arrays was also fabricated by deposition through latex sphere double layers.

PMID- 21727502
TI  - Geometrically tuned and chemically switched wetting properties of silicon
      nanotips.
AB  - The wetting properties of silicon nanotips (SiNTs) are discussed. SiNTs were
      prepared by single step dry etching of silicon wafers in an electron cyclotron
      resonance plasma of silane, methane, argon and hydrogen and water contact angles
      were measured as a function of their aspect ratio (alpha) and the inter-tip
      distance. The hydrophilic nature of the SiNTs is tunable with alpha and the inter
      tip distance. Super-hydrophilicity with water contact angles close to 2 degrees 
      was observed with alpha>12 (length ~1500 nm). Upon coating a 1500 nm long SiNT
      with TiO(2), the water contact angle jumped from 2 degrees  to ~140 degrees ,
      demonstrating a switchover from super-hydrophilic to hydrophobic surface
      properties.

PMID- 21727503
TI  - Enhanced cellular uptake of a glutathione selective fluorogenic probe
      encapsulated in nanoparticles.
AB  - Selective fluorogenic probes for the labelling of intracellular reduced
      glutathione (GSH), i.e. ortho-phthaldialdehyde (OPA) and naphthalene-2,3
      dicarboxaldehyde (NDA), have been encapsulated in polymeric nanoparticles (NPs)
      and the ability of the NPs to enhance uptake of the probe by microbial cells has
      been evaluated. Preparation of the probe-loaded NPs composed of Eudragit((r)) E
      was based on an oil-in-water emulsification solvent evaporation method using an
      ultrasonic probe and polyvinyl alcohol as the surfactant. The encapsulation
      efficiency of the probes in lyophilized NPs was determined using high performance
      liquid chromatography (HPLC). A higher encapsulation rate of NDA than OPA was
      found: 47.6 +/- 9.9 (n = 6) and 2.1 +/- 0.2% (n = 3), respectively. The NDA
      loaded particle diameter and zeta potential were 224.6 +/- 14.7 nm and +40.9 +/-
      6.5 mV, respectively. After 20 min incubation of cultured Candida albicans yeast
      cells with either free NDA or NDA-loaded NPs (final NDA concentration 100 uM),
      cells were harvested and corresponding lysates were analysed using HPLC coupled
      with spectrofluorimetric detection. Incubation of cells with NDA-loaded NPs
      increased intracellular levels of NDA-GSH adduct by about nine-fold in comparison
      with the free probe. Adhesion on the cells and the penetration behaviour of NPs
      loaded with either NDA or fluorescent label (Nile Red) were characterized
      qualitatively by confocal laser scanning microscopy.

PMID- 21727504
TI  - Crystal and electrochemical properties of water dispersed CdS nanocrystals
      obtained via reverse micelles and arrested precipitation.
AB  - Different methods of synthesis for the production of electroactive nanocrystals
      (NCs) for use as labels in DNA sensing systems are presented. They are based on
      two general ways of controlling the formation and growth of the nanoparticles:
      (a) physical restriction of the volume available for the growth of the individual
      nanoparticles by using templates such as reverse micelles; (b) arrested
      precipitation that depends on exhaustion of one of the reactants. The water
      dispersed nanocrystals thus obtained are then characterized by optical or
      electrochemical techniques so as to evaluate the quality of the prepared NCs. A
      novel direct electrochemical stripping detection protocol that involves the use
      of a bismuth modified graphite epoxy composite electrode is developed and applied
      so as to quantify the CdS NCs. The electrochemical study revealed a linear
      dependency of the stripping current upon the concentration of CdS NCs with a
      detection limit of around 10(15) CdS NCs cm(-3). The obtained NCs are of great
      interest for future applications in electrochemical genosensors.

PMID- 21727505
TI  - Vanadium pentoxide nanobelts and nanorolls: from controllable synthesis to
      investigation of their electrochemical properties and photocatalytic activities.
AB  - Uniform V(2)O(5). xH(2)O nanobelts with high aspect ratios and ultra-long
      V(2)O(5). xH(2)O nanorolls with novel scroll-like structures were synthesized on
      a large scale by a simple hydrothermal growth route using NH(4)VO(3) as the raw
      material in the presence of different acids at 180  degrees C for 24 h. Their
      morphologies were observed by scanning electron microscopy (SEM). X-ray powder
      diffraction measurement and thermal gravimetric analysis revealed the composition
      of nanobelts and nanorolls to be V(2)O(5).0.9H(2)O and V(2)O(5).0.6H(2)O,
      respectively. The possible mechanisms of formation of the nanobelts and nanorolls
      were schematically elucidated based on the layered structure of vanadium
      pentoxide. In addition, corresponding anhydrous V(2)O(5) nanostructures with
      better crystallinity were obtained by calcining the precursors of
      V(2)O(5).0.9H(2)O nanobelts or V(2)O(5).0.6H(2)O nanorolls. Furthermore, we have
      investigated the electrochemical intercalation properties with Li(+) and the
      photocatalytic activities of the synthesized V(2)O(5).0.9H(2)O nanobelts,
      V(2)O(5).0.6H(2)O nanorolls and their corresponding post-annealing products. It
      was observed that the morphologies and compositions of the synthesized products
      had an evident influence on the electrochemical intercalation properties with
      Li(+) and photocatalytic activities.

PMID- 21727506
TI  - Dielectrophoretic fabrication and characterization of a ZnO nanowire-based UV
      photosensor.
AB  - Wide-gap semiconductors with nanostructures such as nanoparticles, nanorods,
      nanowires are promising as a new type of UV photosensor. Recently, ZnO (zinc
      oxide) nanowires have been extensively investigated for electronic and
      optoelectronic device applications. ZnO nanowires are expected to have good UV
      response due to their large surface area to volume ratio, and they might enhance
      the performance of UV photosensors. In this paper, a new fabrication method of a
      UV photosensor based on ZnO nanowires using dielectrophoresis is demonstrated.
      Dielectrophoresis (DEP) is the electrokinetic motion of dielectrically polarized
      materials in non-uniform electric fields. ZnO nanowires, which were synthesized
      by nanoparticle-assisted pulsed-laser deposition (NAPLD) and suspended in
      ethanol, were trapped in the microelectrode gap where the electric field became
      higher. The trapped ZnO nanowires were aligned along the electric field line and
      bridged the electrode gap. Under UV irradiation, the conductance of the DEP
      trapped ZnO nanowires exponentially increased with a time constant of a few
      minutes. The slow UV response of ZnO nanowires was similar to that observed with
      ZnO thin films and might be attributed to adsorption and photodesorption of
      ambient gas molecules such as O(2) or H(2)O. At higher UV intensity, the
      conductance response became larger. The DEP-fabricated ZnO nanowire UV
      photosensor could detect UV light down to 10 nW cm(-2) intensity, indicating a
      higher UV sensitivity than ZnO thin films or ZnO nanowires assembled by other
      methods.

PMID- 21727507
TI  - Multi-level assemblies of lead sulphide nanorods.
AB  - A new concept of multi-level assemblies of nanorod-based structures has been
      proposed, which could give new insight into the construction of nanorod-based
      complex structures from the bottom up. Multi-level architectures of complex lead
      sulphide (PbS) nanorod-based structures have been realized by a simple and
      general amino acid-mediated approach. First-level structure (multi-arm horn-like
      structure), second-level structure (bi-pyramid structure formed by several horn
      like structures), and third-level structure (multi-pyramid structure formed by
      several pyramid-like structures) can be synthesized with the assistance of
      different amino acids: aspartic acid, serine, and histidine, respectively. The
      amino acids have several functional groups, such as -NH(2) and -COOH, which have
      strong abilities for coordination with the metal ions, and might provide reaction
      sites by coordinating with metal ions to initiate and then confine the assemblies
      of the PbS nanorods. This amino acid-mediated method provides a possibility of
      studying the formation and assembly mechanisms from the bottom up and might open
      a door to constructing complex nanorod-based structures at different levels.

PMID- 21727508
TI  - Two-dimensional stick-slip on a soft elastic polymer: pattern generation using
      atomic force microscopy.
AB  - It has been demonstrated that it is possible to create laterally differentiated
      frictional patterning and three-dimensional structures using an atomic force
      microscope (AFM) probe on the surface of a soft elastic polymer,
      poly(dimethylsiloxane) (PDMS). The resulting effect of contact mode imaging at
      low loading forces (<100 nN), observed in the lateral force mode, revealed a
      homogeneous pattern on the PDMS surface exhibiting higher friction. With higher
      loading forces ([Formula: see text] nN) the effect is non-uniform, resulting in
      structures with depths on the nanometre scale. The topographic and frictional
      data revealed stick-slip responses in both the fast (orthogonal to the long axis
      of the lever) and slow (parallel to the long axis of the lever) directions of
      probe travel from scanning in a raster pattern. The stick-slip events are
      manifested in the form of a series of shallow channels spaced evenly apart on the
      polymer surface. Detailed friction loop analysis acquired during the manipulation
      process showed that the lateral force changed according to the strength of
      trapping of the tip with the polymer surface exhibiting significant in-plane
      deformation due to lateral forces being imposed. An incremental increase in the
      initial loading force resulted in an increase in in-plane displacement and a
      greater spacing between the stick lines/channels in the slow-scan direction. A
      decrease in channel length in the fast-scan direction is also observed as a
      result of an increase in static friction with normal force, resulting in greater
      surface deformation and shorter track length for sliding friction.

PMID- 21727509
TI  - Integration of single-crystalline nanocolumns into highly ordered nanopore
      arrays.
AB  - The arrangement of nanostructures into desired well-ordered architectures is
      crucial for the realization of functional nanodevices and has been the focus of
      current nanotechnology. Existing physical and chemical approaches have the
      ability to assemble nanostructures, but it is still a challenge to arrange basic
      nanostructures into a highly ordered designed pattern. Here, we report a novel
      method to integrate tin-doped indium oxide single-crystalline nanocolumns into
      highly ordered two-dimensional nanopore patterns through radio-frequency
      magnetron sputtering by the aid of porous alumina membranes (PAMs). We have
      further demonstrated that the morphology of the assembled nanopore arrays is
      controllable by adjusting either the PAM configurations or sputtering conditions.
      Our present method provides the possibility of a general approach for nanounit
      integration, and these assembled regular nanopore arrays pave the way for the
      application of novel filters and sensors.

PMID- 21727510
TI  - Utilizing nanofabrication to construct strong, luminescent materials.
AB  - Luminescent materials have been utilized widely in applications from lighting to
      sensing. The new development of technologies based on luminescence requires the
      materials to have high luminescence efficiency and mechanical strength. In this
      paper, we report the fabrication of luminescent materials possessing high
      mechanical strength by nanofabrication with polyvinyl alcohol used as a
      stabilizer or coupling agent. X-ray diffraction and high-resolution transmission
      microscope observations reveal that the nanocomposite sample contains ZnS and ZnO
      nanoparticles as well as kozoite and sodium nitrate. The mechanical strength and
      hardness of these nanocomposites are reasonably high, higher than polycarbonate
      and some carbon nanotube reinforced nanocomposites. Strong luminescence is
      observed in the new nanocomposites and the luminescence intensity does not
      degrade following up to 30 min of x-ray irradiation. Our results indicate that
      nanofabrication may provide a good method to improve the mechanical strength of
      luminescent materials for some applications in which high-strength luminescent
      materials are needed.

PMID- 21727511
TI  - Influence of Si interdiffusion on carbon-induced growth of Ge quantum dots: a
      strategy for tuning island density.
AB  - We have studied the epitaxial growth of self-assembled Ge quantum dots when a
      submonolayer of carbon is deposited on a Ge wetting layer (WL) prior to the
      growth of the dots. Using atomic-force microscopy combined with optical
      techniques like Raman and ellipsometry, we performed a systematic study of the
      role played by thermally activated Si interdiffusion on dot density, composition
      and morphology, by changing only the growth temperature T(WL) of the WL.
      Strikingly, we observe that higher dot densities and a narrower size distribution
      are achieved by increasing the deposition temperature T(WL), i.e. by enhancing Si
      interdiffusion from the substrate. We suggest a two-stage growth procedure for
      fine tuning of dot topography (density, shape and size) useful for possible
      optoelectronic applications.

PMID- 21727512
TI  - Optical properties and carrier dynamics of self-assembled GaN/Al(0.11)Ga(0.89)N
      quantum dots.
AB  - GaN quantum dots were grown on an Al(0.11)Ga(0.89)N buffer layer by using flow
      rate modulation epitaxy. The Stranski-Krastanov growth mode was identified by an
      atomic force microscopy study. The thickness of the wetting layer is about 7.2
      monolayers. The temperature dependent photoluminescence studies showed that at
      low temperature the localization energy, which accounts for de-trapping of
      excitons, decreases with the reducing dot size. The decrease in emission
      efficiency at high temperature is attributed to the activation of carriers from
      the GaN dot to the nitrogen vacancy (V(N)) state of the Al(0.11)Ga(0.89)N barrier
      layer. The activation energy decreases with reducing dot size.

PMID- 21727513
TI  - Sonochemical synthesis of PbWO(4) crystals with dendritic, flowery and star-like
      structures.
AB  - Lead tungstate single crystals with dendritic, flowery and star-like structures
      have been prepared via a facile, ethylene glycol (EG)-assisted sonochemical
      method. The concentrations of EG and ultrasound irradiation were found to play
      crucial roles in the morphology control of the final products. The growth process
      was investigated by carefully following time-dependent experiments, and the
      oriented attachment process accompanying Ostwald ripening was proposed for the
      possible formation mechanism. The optical properties, such as the Raman spectra
      and photoluminescence (PL) spectra, of the obtained PbWO(4) crystals were
      studied.

PMID- 21727514
TI  - Rare earth ions and Ge nanocrystals in SiO(2).
AB  - Experimental studies of Ge nanocrystals embedded in SiO(2) films doped with Er
      and Yb deposited by rf-magnetron sputtering are presented. Although inter-band
      photoluminescence (PL) from the Ge nanocrystals is not observed, it is
      nevertheless found that the presence of Ge nanocrystals is crucial for obtaining
      light emission from Er(3+) and Yb(3+). For both kinds of rare earth ions, the
      intensity of the related PL line has a maximum after heat treatment at 800 
      degrees C, and the PL excitation spectra for the two cases are very similar. This
      suggests that the presence and the structure of the nanocrystals are important
      for the efficiency of PL from Er(3+) and Yb(3+). Experiments performed with
      multilayer structures of Ge nanocrystals and SiO(2) show that the optically
      active rare earth ions are located in the SiO(2) layers, and not inside the Ge
      nanocrystals. The mechanism of energy transfer from Ge nanocrystals to the rare
      earth ions is found to be non-optical.

PMID- 21727515
TI  - Nanostructured mesoporous tungsten oxide films with fast kinetics for
      electrochromic smart windows.
AB  - A potential driven self-assembly of sodium dodecyl sulfate/tungsten oxide
      aggregates at the electrolyte-electrode interface followed by template extraction
      and annealing yielded mesoporous thin films of electrochromic tungsten oxide
      (WO(3)). Electron microscopy images revealed that the films are characterized by
      a hitherto unreported hybrid structure comprising nanoparticles and nanorods with
      a tetragonal crystalline phase of WO(3) with the measured lattice parameters: a =
      0.53 nm and c = 0.37 nm. In addition to pentagonal voids characteristic of the
      tetragonal WO(3) phase at the lattice scale, open channels and pores of 5-10 nm
      in diameter lie between the nanoparticles, which cumulatively promote rapid
      charge transport through the film. This resulted in colouration efficiency
      (eta(max)~90 cm(2) C(-1) at lambda = 900 nm) and switching kinetics (colouration
      time =  3 s and bleaching time =  2 s for a 50% change in transmittance) higher
      and faster than previously reported values for mesoporous WO(3) films. Repetitive
      cycling between the clear and blue states has no deleterious effect on the
      electrochromic performance of the film, which is suggestive of its potential as a
      cathode in practical electrochromic windows.

PMID- 21727516
TI  - Fabrication of zinc oxide nanostructures using solvent-assisted capillary
      lithography.
AB  - We present a simple solvent-assisted capillary molding method to fabricate zinc
      oxide (ZnO) nanostructures using an ultraviolet (UV) curable polyurethane
      acrylate (PUA) mold. A thin film of the ZnO sol-gel precursor solution in methyl
      alcohol was prepared by spin coating on a solid substrate and subsequently a
      nanopatterned PUA mold was brought into conformal contact with the substrate
      under slight physical pressure (~3.5 bar). After annealing at 230  degrees C for
      4 h, well-defined ZnO nanostructures formed with feature size down to ~50 nm,
      aided by capillary rise and solvent evaporation. It was found that the height of
      capillary rise depended highly on the applied pressure. A simple experimental
      setup was devised to examine the effects of pressure, revealing that the optimum
      pressure ranged from 3.5 bar to 5 bar. Also, ZnO nanorods could be selectively
      grown on patterned regions using the seed layer as a pseudocatalyst when the
      width of the seed layer was larger than ~200 nm.

PMID- 21727517
TI  - ZnO nanoparticles embedded in sapphire fabricated by ion implantation and
      annealing.
AB  - ZnO nanoparticles were fabricated in sapphire (alpha-Al(2)O(3) single crystal) by
      Zn ion implantation (48 keV) at an ion fluence of 1 * 10(17) cm(-2) and
      subsequent thermal annealing in a flowing oxygen atmosphere. Transmission
      electron microscopy (TEM) analysis revealed that metallic Zn nanoparticles of 3
      10 nm in dimensions formed in the as-implanted sample and that ZnO nanoparticles
      of 10-12 nm in dimensions formed after annealing at 600  degrees C. A broad
      absorption band, peaked at 280 nm, appeared in the as-implanted crystal, due to
      surface plasma resonance (SPR) absorption of metallic Zn nanoparticles. After
      annealing at 600  degrees C, ZnO nanoparticles resulted in an exciton absorption
      peak at 360 nm. The photoluminescence (PL) of the as-implanted sample was very
      weak when using a He-Cd 325 nm line as the excitation source. However, two
      emission peaks appeared in the PL spectrum of ZnO nanopraticles, i.e., one
      ultraviolet (UV) peak at 370 nm and the other a green peak at 500 nm. The
      emission at 500 nm is stronger and has potential applications in green/blue light
      emitting devices.

PMID- 21727518
TI  - Controlled synthesis of 2D Au nanostructure assembly with the assistance of
      sulfonated polyaniline nanotubes.
AB  - A wet chemical approach is used successfully to produce nanostructured Au
      material by the reduction of sulfonated polyaniline (SPANI) nanotubes. The Au
      nanostructures obtained are composed of single crystal Au nanoplates, which are
      aggregated layer-by-layer into stacks or edge-on-face into clusters at various
      conditions. The Au nanoplate diameter and thickness can be conveniently
      controlled in the range of 100 nm to 2 um and 10 to 30 nm, respectively, with no
      accompanying single Au nanoparticles being observed. The formation of the Au
      nanostructures was controlled by the degradation of SPANI. The gradually and
      slowly released segments of SPANI served as the reductant during the growth of
      the 2D Au nanostructures.

PMID- 21727519
TI  - Effects of annealing on the structural and mechanical properties of electrospun
      polymeric nanofibres.
AB  - Biodegradable polymeric nanofibres produced by electrospinning have been used as
      scaffolds for tissue engineering. Before these nanofibrous scaffolds can be
      implanted into the human body, it is important to know if the individual
      nanofibres are strong enough to withstand the forces exerted by the cells as they
      grow and migrate on the scaffold. However, due to the small size of the
      nanofibres, it is a challenge to characterize the mechanical properties of
      individual nanofibres. Therefore, we aim to mechanically characterize a single
      nanofibre using both a tensile test and a nanoscale three-point bend test. As
      some scaffolds may be heat-treated by annealing to enhance the stiffness and
      strength of the nanofibres, we also investigate the effects of annealing on the
      structural and mechanical properties of single nanofibres. The material
      properties of as-spun and annealed nanofibres were studied using differential
      scanning calorimetry and atomic force microscopy. Annealing was found to increase
      the Young's modulus of the nanofibre mainly due to the increase in crystallinity
      and the change in morphology from a purely fibrillar structure to a mixture of
      fibrillar and nano-granular structure with enhanced interfibrillar bonding.

PMID- 21727520
TI  - Thermally assisted tunnelling in ambipolar field-effect transistors based on
      fullerene peapod bundles.
AB  - We report the first detailed studies of the electrical transport behaviour of
      C(70) fullerene peapod bundles at various temperatures from 400 K down to 4 K.
      With electrical breakdown, we have prepared ambipolar (i.e. both p- and n-type)
      field-effect transistors (FETs) using fullerene peapod bundles with high levels
      of performance. This paper focuses on the role of the Schottky barrier and the
      thermal activation energy in the transport behaviour of fullerene bundles. The
      temperature dependence of our measurements reveals that transport is dominated by
      thermally assisted tunnelling in fullerene bundles at low temperature.

PMID- 21727521
TI  - DNA-directed synthesis of zinc oxide nanowires on carbon nanotube tips.
AB  - This paper describes a class of three component hybrid nanowires templated by DNA
      directed self-assembly. Through the modification of carbon nanotube (CNT) termini
      with synthetic DNA oligonucleotides, gold nanoparticles are delivered, via DNA
      hybridization, to CNT tips that then serve as growth sites for zinc oxide (ZnO)
      nanowires. The structures we have generated using DNA templating represent an
      advance toward building higher order sequenced one dimensional nanostructures
      with rational control.

PMID- 21727522
TI  - Galvanic deposition of nanocrystalline ZnO thin films from a ZnO-Zn(OH)(2) mixed
      phase precursor on p-Si substrate.
AB  - A galvanic technique for the deposition of ZnO thin films is reported. The
      depositions were carried out on p-type single-crystal silicon substrates at room
      temperature, from a solution of ZnSO(4), where the Zn rod acted as a sacrificing
      anode and p-Si was the cathode. The deposition of ZnO by this method is pH
      sensitive, and a pH between 4 and 5 is found to be optimum for film deposition.
      This deposition technique is simple, inexpensive and can be carried out at room
      temperature. X-ray diffraction (XRD), scanning electron microscopy (SEM) and
      atomic force microscopy (AFM) studies revealed the nanocrystalline structure of
      the films. The resistivity of the annealed ZnO films was determined by the Van
      der Pauw measurement technique.

PMID- 21727523
TI  - Aligned silver nanorod arrays for surface-enhanced Raman scattering.
AB  - Silver nanorods were prepared by a seed-mediated growth approach, and self
      assembled into two-dimensional ordered arrays on glass substrates. The
      polarization-dependent optical responses of the rods were measured, which
      indicated ordered alignment. These arrays were evaluated as potential surface
      enhanced Raman spectroscopy (SERS) substrates using trans-bis(4-pyridyl)ethylene
      molecules. The SERS signals were observed to be enhanced with the increase of the
      aspect ratio of the Ag nanorod, and this was mainly attributed to the local field
      enhancement. The lateral arrangement of the Ag nanorod arrays was also partially
      responsible for the SERS enhancement.

PMID- 21727524
TI  - Effect of reducing atmosphere on the magnetism of Zn(1-x)Co(x)O (0<=x<=0.10)
      nanoparticles.
AB  - We report the crystal structure and magnetic properties of Zn(1-x)Co(x)O
      (0<=x<=0.10) nanoparticles synthesized by heating metal acetates in organic
      solvent. The nanoparticles were crystallized in the wurtzite ZnO structure after
      annealing in air and in a forming gas (Ar95% + H5%). The x-ray diffraction and x
      ray photoemission spectroscopy (XPS) data for different Co content show clear
      evidence for the Co(2+) ions in tetrahedral symmetry, indicating the substitution
      of Co(2+) in the ZnO lattice. However, samples with x = 0.08 and higher cobalt
      content also indicate the presence of Co metal clusters. Only those samples
      annealed in the reducing atmosphere of the forming gas, that showed the presence
      of oxygen vacancies, exhibited ferromagnetism at room temperature. The air
      annealed samples remained non-magnetic down to 77 K. The essential ingredient in
      achieving room temperature ferromagnetism in these Zn(1-x)Co(x)O nanoparticles
      was found to be the presence of additional carriers generated by the presence of
      the oxygen vacancies.

PMID- 21727525
TI  - Standing [111] gold nanotube to nanorod arrays via template growth.
AB  - Standing [111]-oriented crystalline gold nanotube (AuNT) and nanorod (AuNR)
      arrays using electrochemical deposition through template growth are reported.
      Segments of single crystal and bamboo-like crystalline AuNR arrays with growing
      direction of [111], having a diameter of 100-150 nm and a length of 10 um,
      standing perpendicular to Ti metal foil substrates, are synthesized. The as
      synthesized AuNTs and AuNRs are characterized by powder and five circle x-ray
      diffractometry, UV-visible molecular absorption spectrometry, field emission
      scanning electron microscopy, and transmission electron microscopy. AuNRs and
      AuNTs are formed by starting with a tube and the wall of the tube gets
      progressively thicker and eventually sealed up to form nanorods. Optical
      absorption at 548 and 578 nm wavelength for gold nanotubes and nanorods,
      respectively, caused by the transverse (width) mode is identified.

PMID- 21727526
TI  - Fabrication, structural characterization and photoluminescence of Q-1D
      semiconductor ZnS hierarchical nanostructures.
AB  - Quasi-one-dimensional semiconductor ZnS hierarchical nanostructures have been
      fabricated by thermal evaporation of a mixture of ZnS nanopowders and Sn powders.
      Sn nanoparticles are located at or close to the tips of the nanowires (or
      nanoneedles) and served as the catalyst for quasi-one-dimensional ZnS
      nanostructure growth by a vapour-liquid-solid mechanism. The morphology and
      microstructure of the ZnS hierarchical nanostructures were measured by scanning
      electron microscopy and high-resolution transmission electron microscopy. The
      results show that a large number of ZnS nanoneedles were formed on the outer
      shells of a long and straight ZnS axial nanowire. The ZnS axial nanowires grow
      along the [001] direction, and ZnS nanoneedles are aligned over the surface of
      the ZnS nanowire in the radial direction. The room temperature photoluminescence
      spectrum exhibits a UV weak emission centred at 337 nm and one blue emission
      centred at 436 nm from the as-synthesized single-crystalline semiconductor ZnS
      hierarchical nanostructures.

PMID- 21727527
TI  - Stamp design effect on 100 nm feature size for 8 inch NanoImprint lithography.
AB  - Sub-100 nm resolution on a 200 mm silicon stamp has been hot embossed into
      commercial Sumitomo NEB 22 resist. A single pattern, exposed with electron beam
      lithography, has been considered to define the stamp and thus make it possible to
      point out the impact of stamp design on the printing. These results may be
      considered as a first attempt to define rules to solve the proximity printing
      effects (PPEs). Moreover, a large range of initial resist thickness, from 56 to
      506 nm, has been spin coated to assess the effect of polymer flow properties for
      the stamp cavity filling and the printed defects. A detailed analysis of the
      printed resist in dense hole patterns showed that the application volume
      conservation is enough to calculate the residual layer thickness as the height of
      the printed resist feature. Good accordance has been obtained between the
      theoretical approach and experimental results. Moreover, the impact of the
      pattern symmetry breakdown on mould deformation is clearly shown in this paper in
      the printed areas as well as in the unprinted areas.

PMID- 21727528
TI  - AFM study of glucagon fibrillation via oligomeric structures resulting in
      interwoven fibrils.
AB  - Glucagon is a 29-residue amphiphatic hormone involved in the regulation of blood
      glucose levels in conjunction with insulin. In concentrated aqueous solutions,
      glucagon spontaneously aggregates to form amyloid fibrils, destroying its
      biological activity. In this study we utilize the atomic force microscope (AFM)
      to elucidate the fibrillation mechanism of glucagon at the nanoscale under acidic
      conditions (pH 2.0) by visualizing the nanostructures of fibrils formed at
      different stages of the incubation. Hollow disc-shaped oligomers form at an early
      stage in the process and subsequently rearrange to more solid oligomers. These
      oligomers co-exist with, and most likely act as precursors for, protofibrils,
      which subsequently associate to form at least three different classes of higher
      order fibrils of different heights. A repeat unit of around 50 nm along the main
      fibril axis suggests a helical arrangement of interwoven protofibrils. The
      diversity of oligomeric and fibrillar arrangements formed at pH 2.0 complements
      previous spectroscopic analyses that revealed that fibrils formed under different
      conditions can differ substantially in stability and secondary structure.

PMID- 21727529
TI  - Interface study on heterostructured GaP-GaAs nanowires.
AB  - The interface chemical composition of heterostructured GaP-GaAs nanowire segments
      was studied by the use of energy-dispersive x-ray analysis. An arsenic-rich tail
      in the GaP segments following GaAs could be minimized by reducing the AsH(3)
      molar fraction and the growth rate. For the temperature regime used for vapour
      liquid-solid growth, we observe the opposite trend on interface sharpness
      compared to high-temperature layer-by-layer growth, that is, the sharpness of the
      interface improves with reducing temperature.

PMID- 21727530
TI  - Application of spectromicroscopy tools to explore local origins of sensor
      activity in quasi-1D oxide nanostructures.
AB  - We have tested a range of imaging and spectroscopic techniques to address their
      ability to locally explore the interplay between surface reactivity and transport
      properties of the metal oxide nanostructure wired as a chemiresistor and chemi
      FET. In particular, we used scanning surface potential microscopy (SSPM) to
      monitor the spatial and temporal particularities of the dc potential
      distributions in an operating device. We also successfully implemented
      synchrotron radiation-based photoelectron emission microscopy (PEEM) to explore
      submicron lateral compositional and electronic (work function) inhomogeneity on
      the surface of an individual nanowire sensor. These results open new avenues to
      visualize and spectroscopically address the chemical phenomena on an individual
      quasi-1D nanostructure both in real time and at nano- and mesoscopic level.

PMID- 21727531
TI  - Synthesis of silver nanoparticles using the polyol process and the influence of
      precursor injection.
AB  - Spherical silver nanoparticles with various sizes and standard deviations were
      synthesized by the polyol process. Two different synthesis methods were compared
      in order to investigate the influence of reaction parameters on the resulting
      particle size and its distribution. In the precursor heating method, wherein a
      solution containing silver nitrate was heated to the reaction temperature, the
      ramping rate was determined to be a critical parameter affecting the particle
      size. In contrast, in the precursor injection method, in which a silver nitrate
      aqueous solution was injected into hot ethylene glycol, because of rapid
      nucleation, the injection rate and the reaction temperature were important
      factors in terms of reducing the particle size and attaining monodispersity.
      Silver nanoparticles with a size of 17 +/- 2 nm were obtained at an injection
      rate of 2.5 ml s(-1) and a reaction temperature of 100  degrees C.

PMID- 21727532
TI  - Temperature conditions for GaAs nanowire formation by Au-assisted molecular beam
      epitaxy.
AB  - Molecular beam epitaxial growth of GaAs nanowires using Au particles as a
      catalyst was investigated. Prior to the growth during annealing, Au alloyed with
      Ga coming from the GaAs substrate, and melted. Phase transitions of the resulting
      particles were observed in situ by reflection high-energy electron diffraction
      (RHEED). The temperature domain in which GaAs nanowire growth is possible was
      determined. The lower limit of this domain (320  degrees C) is close to the
      observed catalyst solidification temperature. Below this temperature, the
      catalyst is buried by GaAs growth. Above the higher limit (620  degrees C), the
      catalyst segregates on the surface with no significant nanowire formation. Inside
      this domain, the influence of growth temperature on the nanowire morphology and
      crystalline structure was investigated in detail by scanning electron microscopy
      and transmission electron microscopy. The correlation of the nanowire morphology
      with the RHEED patterns observed during the growth was established. Wurtzite GaAs
      was found to be the dominant crystal structure of the wires.

PMID- 21727533
TI  - Growth of SnO(2) nanocrystals controlled by erbium doping in silica.
AB  - We investigate the effects of erbium doping on SnO(2) nanoclustering in Sn-doped
      silica. Vibrational spectroscopy data from Raman and infrared absorption
      measurements show nanostructuring effects on the SnO(2) nanophase. Ultraviolet
      absorption spectra evidence a gap shift ascribable to size-dependent quantum
      confinement, also suggesting a role of erbium doping in determining cluster sizes
      and the amount of localized states on the nanophase boundary. Transmission
      electron microscopy confirms and details the spectroscopic data. As a result of
      these measurements, we find that the nanocrystal size distribution becomes
      narrower, increasing the erbium concentration, while the density of localized
      states at the nanocrystal surface decreases. The distribution of erbium ions
      among the possible environments is then examined through simultaneous
      spectroscopy of luminescence excited by nanocrystal-to-erbium energy transfer and
      the absorption of nanocrystal luminescence by erbium ions. This analysis shows
      that erbium behaves as an extrinsic nucleation centre of the SnO(2) nanophase at
      low doping levels, whereas at high concentrations it modifies the matrix,
      hindering the growth of SnO(2) crystals and passivating the interface.

PMID- 21727534
TI  - Observation of Ga droplet formation on (311)A and (511)A GaAs surfaces.
AB  - Using (100) GaAs substrates as a reference, we present a study of the formation
      of Ga droplets on (311)A and (511)A GaAs substrates in which the effect of both
      the substrate temperature and the amount of Ga supplied on the droplet density
      and height for the three different surfaces have been investigated. Droplets on
      (100) substrates show a round shape; however, they appear as elongated balls with
      tails along the [Formula: see text] direction of the (311)A substrate and the
      [Formula: see text] direction of the (511)A substrate. It has been found that the
      Ga droplets on (511)A surfaces have lower densities and higher heights than those
      on (100) substrates. In contrast, Ga droplets on (311)A surfaces have lower
      heights and much higher densities compared to those for both (100) and (511)A. We
      observed that the decrease in the droplet density with increasing growth
      temperature for both (311)A and (511)A is more than twice that for the (100)GaAs
      surface due to the larger drop in the nucleation rate. Based on these
      observations, we offer a physical explanation based on the thermodynamics and the
      anisotropy of the high-index surfaces.

PMID- 21727535
TI  - Hybrid nanocrystal/polymer solar cells based on tetrapod-shaped CdSe(x)Te(1-x)
      nanocrystals.
AB  - A series of ternary tetrapodal nanocrystals of CdSe(x)Te(1-x) with x = 0 (CdTe),
      0.23, 0.53, 0.78, 1 (CdSe) were synthesized and used to fabricate hybrid
      nanocrystal/polymer solar cells. Herein, the nanocrystals acted as electron
      acceptors, and poly(2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene) (MEH
      PPV) was used as an electron donor. It was found that the open circuit voltage
      (V(oc)), short-circuit current (J(sc)) and power conversion efficiency (eta) of
      the devices all increased with increasing Se content in the CdSe(x)Te(1-x)
      nanocrystals under identical experimental conditions. The solar cell based on the
      blend of tetrapodal CdSe nanocrystals and MEH-PPV (9:1 w/w) showed the highest
      power conversion efficiency of 1.13% under AM 1.5, 80 mW cm(-2), and the maximum
      incident photon to converted current efficiency (IPCE) of the device reached 47%
      at 510 nm. The influence of nanocrystal composition on the photovoltaic
      properties of the hybrid solar cells was explained by the difference of the band
      level positions between MEH-PPV and the nanocrystals.

PMID- 21727536
TI  - Luminescent properties and characterization of one dimensional Gd(2)O(3):Eu(3+)
      phosphor nano-wire for field emission application.
AB  - Gd(2)O(3):Eu(3+) nano-wire phosphors embedded in SBA-15 silica templates were
      synthesized using a combination of the sol-gel method and hydrothermal reactions
      followed by a sintering process at 1000  degrees C. The crystal structure of
      Gd(2)O(3):Eu(3+) was confirmed using x-ray diffraction. Observation using
      transmission electron microscopy shows that the nano-wire diameters were very
      uniform in the 7-9 nm range. In comparison with bulk Gd(2)O(3):Eu(3+) materials,
      we found that the photo-luminescent property of the nano-wire was different. The
      analysis shows that the main nano-wire emission peaks were at 585, 597, 613 and
      620 nm. The CIE value (x = 0.62, y = 0.38) indicates that the nano-wire emitted a
      pink colour and not red as for the bulk material. The field emission experimental
      results agreed well with the photo-luminescent analysis results.

PMID- 21727537
TI  - Formation of a nanogroove-striped NiO surface using atomic steps.
AB  - A nanogroove-striped pattern was formed on a NiO film surface. The periodic
      nanopattern was successfully obtained over the entire surface via high
      temperature annealing of the epitaxial NiO thin film, which was grown on an
      atomically stepped sapphire substrate at low temperature. The depth, width and
      interval of straight nanogrooves were about 3 nm, 35 nm and about 100 nm,
      respectively. The periodicity of the stripe agrees well with that of the atomic
      steps of the substrate.

PMID- 21727538
TI  - Sustained release of doxorubicin from zeolite-magnetite nanocomposites prepared
      by mechanical activation.
AB  - Nanocomposites consisting of magnetite and FAU zeolite with a high surface area
      and adsorption capacity have been prepared by mechanical activation using high
      energy milling at room temperature. FTIR results, as well as HRTEM, EFTEM, and
      XPS measurements, show that the resulting magnetic nanoparticles are covered by a
      thin aluminosilicate coating. A saturation magnetization as high as 16 emu g(-1)
      and 94.2 Oe of coercivity were observed for the obtained composites. The main
      advantages of this synthesis procedure are (i) simplicity of the preparation
      procedure, (ii) prevention of agglomeration of the magnetite nanoparticles to a
      large extent, and (iii) absence of free magnetite outside the zeolitic matrix. In
      addition, in vitro experiments revealed that the nanoparticles prepared were able
      to store and release substantial amounts of doxorubicin. In view of these
      advantages, these magnetic nanoparticles can be considered as potential
      candidates for drug-delivery applications.

PMID- 21727539
TI  - Controlling semiconductor nanoparticle size distributions with tailored
      ultrashort pulses.
AB  - The laser generation of size-controlled semiconductor nanoparticle formation
      under gas phase conditions is investigated. It is shown that the size
      distribution can be changed if picosecond pulse sequences of tailored ultra short
      laser pulses (<200 fs) are employed. By delivering the laser energy in small
      packages, a temporal energy flux control at the target surface is achieved, which
      results in the control of the thermodynamic pathway the material takes. The
      concept is tested with silicon and germanium, both materials with a predictable
      response to double pulse sequences, which allows deduction of the materials'
      response to complicated pulse sequences. An automatic, adaptive learning
      algorithm was employed to demonstrate a future strategy that enables the
      definition of more complex optimization targets such as particle size on
      materials less predictable than semiconductors.

PMID- 21727540
TI  - Structural and optical properties of single-crystalline ZnO nanorods grown on
      silicon by thermal evaporation.
AB  - The growth of perfectly hexagonal-shaped ZnO nanorods, with Zn-terminated (0001)
      facets bounded with [Formula: see text] surfaces, has been performed on nickel
      coated Si(100) substrate via thermal evaporation using metallic zinc powder and
      oxygen. Detailed structural investigations confirmed that the synthesized
      nanorods are single crystalline with the wurtzite hexagonal phase and
      preferentially grow along the c-axis direction. Raman spectra of the as-grown ZnO
      nanorods showed an optical-phonon E(2) mode at 438 cm(-1), indicating that as
      grown nanostructures are in good crystallinity with the wurtzite hexagonal phase.
      The ZnO nanorods were found to show strong band edge emission with very weak or
      no deep-level emission, as shown by photoluminescence measurements. The clear
      observation of free excitons at low temperatures (13-50 K) indicates that the as
      grown ZnO nanorods are of high quality.

PMID- 21727541
TI  - Charge trapping phenomena of tetraethylorthosilicate thin film containing Si
      nanocrystals synthesized by solid-state reaction.
AB  - In this work, we report on the fabrication of tetraethylorthosilicate (TEOS) thin
      dielectric film containing silicon nanocrystals (Si nc), synthesized by solid
      state reaction, in a capacitor structure. A metal-insulator-semi-conductor (MIS)
      capacitor, with 28 nm thick Si nc in a TEOS thin film, has been fabricated. For
      this MIS, both electron and hole trapping in the Si nc are possible, depending on
      the polarity of the bias voltage. A V(FB) shift greater than 1 V can be
      experienced by a bias voltage of 16 V applied to the metal electrode for 1 s.
      Though there is no top control oxide, the discharge time for 10% of charges can
      be up to 4480 s when it is biased at 16 V for 1 s. It is further demonstrated
      that charging and discharging mechanisms are due to the Si nc rather than the
      TEOS oxide defects. This form of Si nc in a TEOS thin film capacitor provides the
      possibility of memory applications at low cost.

PMID- 21727542
TI  - Influence of the molecular weight and imprint conditions on the formation of
      capillary bridges in nanoimprint lithography.
AB  - Sub-100 nm patterns can be duplicated by nanoimprint lithography with high
      reproducibility, even on 200 mm wafers. Nevertheless, several problems have to be
      solved before this technique reaches a mature state for industrial applications.
      Several kinds of defect appear frequently in printed polymers. Some of them are
      induced by capillary effects and are related to mould deformation. Capillary
      bridges are observed on the flat surfaces around the pattern areas, or inside the
      printed structures. In this paper, the influence of the polymer molecular weight
      (M(w)) on the capillary bridge distribution is presented. It will be shown that
      for smaller M(w), they appear first around the pattern areas and move towards the
      structures more rapidly. It is also demonstrated that this evolution depends
      directly on the printing temperature and pattern filling related to the feature
      density and the film thickness. Finally, it is shown that the influence of these
      parameters is related to the polymer viscosity, which is the dominant property of
      the capillary effects, and a trade-off has to be made between the limitation due
      to the capillary bridges, the decrease of the temperature, which is important to
      reduce the cycle time, and the sticking defects.

PMID- 21727543
TI  - Silicon adsorption in defective carbon nanotubes: a first principles study.
AB  - The electronic and structural properties of an (8, 0) single-walled carbon
      nanotube (SWNT) with a single vacancy and interacting with a Si atom are studied
      using first principles calculations based on the density-functional theory.
      Initially, the Si atom is positioned in the site above the vacancy, with its
      position fixed until the nanotube geometry is fully relaxed. After that, the Si
      atom approaches the tube and it is shown that one C atom is displaced outwards
      forming a bump. The final configuration, as well as each step of the process, is
      studied in detail and the resulting band structures and the total charge
      densities are systematically analysed.

PMID- 21727544
TI  - Electronic excitation energies of Zn(i)S(i) nanoparticles.
AB  - The excitation energies of small ZnS nanoclusters characterized in previous
      studies have been calculated using TDDFT. The relativistic pseudopotentials of
      Stevens et al have been used, including Zn 4s(2) electrons and S 3s(2) and 3p(4)
      electrons as valence electrons. Results obtained with these pseudopotentials are
      compared to those obtained considering also Zn 3s(2)3p(6)3d(10) electrons in the
      valence part, and demonstrated to be consistent. The results show that spheroid
      like bubble structures have absorption energies in the range of 5-5.3 eV for
      small sizes, which decreases to 5 eV with increasing particle size.

PMID- 21727545
TI  - Particle growth mechanisms in Ag-ZrO(2) and Au-ZrO(2) granular films obtained by
      pulsed laser deposition.
AB  - Thin films consisting of Ag and Au nanoparticles embedded in amorphous ZrO(2)
      matrix were grown by pulsed laser deposition in a wide range of metal volume
      concentrations in the dielectric regime (0.08<x(Ag)<0.28 and 0.08<x(Au)<0.52).
      High resolution transmission electron microscopy (TEM) showed regular
      distribution of spherical Au and Ag nanoparticles having very sharp interfaces
      with the amorphous matrix. Mean particle size determined from x-ray diffraction
      agreed with direct TEM observation. The silver mean diameter increases more
      abruptly with metal volume content than that corresponding to gold particles
      prepared under the same conditions. Two mechanisms of particle growth are
      observed: nucleation and particle coalescence, their relative significance being
      different in both granular systems, which yields very different values of the
      percolation threshold (x(c)(Ag)~0.28 and x(c)(Au)~0.52).

PMID- 21727546
TI  - The effect of potassium on the adsorption of gold on the TiO(2)(110)-1 * 1
      surface.
AB  - Density functional theory (DFT) total-energy calculations have been used to
      investigate the effect of potassium on the adsorption geometry of gold on a
      TiO(2)(110)- 1 * 1 surface. The gold prefers to sit between the two bridge oxygen
      atoms above the sixfold titanium atom. The addition of potassium significantly
      affects the bonding geometry of the gold. Potassium displaces gold from the
      bridge site and causes its migration to the top of the fivefold titanium atom.
      Our calculations suggest that potassium is bonded to the bridging oxygen atoms,
      and to the sixfold titanium atom as well as to gold. This excludes the formation
      of a K(2)O-like compound at the surface.

PMID- 21727547
TI  - Emission properties of colloidal quantum dots on polyelectrolyte multilayers.
AB  - We present steady state and time-resolved photoluminescence (PL) characteristics
      of differently charged CdTe quantum dots (QDs) adsorbed onto a polyelectrolyte
      (PE) multilayer. The PE multilayer is built up using a layer-by-layer assembly
      technique. We find that the diffusion of the QDs into the PE multilayer is an
      important factor in the case of 3-mercapto-1, 2-propanediol stabilized QDs
      (neutral surface charge), resulting in a ~31-fold enhancement in PL intensity
      accompanied by a blue shift in the PL spectra and an increase in decay lifetime
      from 3.74 ns to a maximum of 11.65 ns. These modified emission properties are
      attributed to the enhanced surface related emission resulting from the
      interaction of the QD's surface with the PE. We find that diffusion does not
      occur for thioglycolic acid (TGA) stabilized QDs (negative surface charge) or 2
      mercaptoethylamine stabilized QDs (positive surface charge), indicating
      localization of the QDs on top of the PE multilayer. However, the PL lifetime of
      the TGA stabilized QDs decreases from 9.58 to 5.78 ns with increasing PE
      multilayer thickness. This provides evidence for increased intrinsic exciton
      recombination relative to surface related emission, which results in an overall
      reduction in the average lifetime. Our studies indicate the importance of the QD
      surface charge in determining the interaction with the PE multilayers and the
      subsequent modification of the QD emission properties.

PMID- 21727548
TI  - Flexible carbon nanotube sensors for nerve agent simulants.
AB  - Chemiresistor-based vapour sensors made from network films of single-walled
      carbon nanotube (SWNT) bundles on flexible plastic substrates (polyethylene
      terephthalate, PET) can be used to detect chemical warfare agent simulants for
      the nerve agents Sarin (diisopropyl methylphosphonate, DIMP) and Soman (dimethyl
      methylphosphonate, DMMP). Large, reproducible resistance changes (75-150%), are
      observed upon exposure to DIMP or DMMP vapours, and concentrations as low as 25
      ppm can be detected. Robust sensor response to simulant vapours is observed even
      in the presence of large equilibrium concentrations of interferent vapours
      commonly found in battle-space environments, such as hexane, xylene and water (10
      000 ppm each), suggesting that both DIMP and DMMP vapours are capable of
      selectively displacing other vapours from the walls of the SWNTs. Response to
      these interferent vapours can be effectively filtered out by using a 2 um thick
      barrier film of the chemoselective polymer polyisobutylene (PIB) on the SWNT
      surface. These network films are composed of a 1-2 um thick non-woven mesh of
      SWNT bundles (15-30 nm diameter), whose sensor response is qualitatively and
      quantitatively different from previous studies on individual SWNTs, or a network
      of individual SWNTs, suggesting that vapour sorption at interbundle sites could
      be playing an important role. This study also shows that the line patterning
      method used in device fabrication to obtain any desired pattern of films of SWNTs
      on flexible substrates can be used to rapidly screen simulants at high
      concentrations before developing more complicated sensor systems.

PMID- 21727549
TI  - Thermally assisted semiconductor-like to insulator transition in gold-poly(methyl
      methacrylate) nanocomposites.
AB  - Gold-polymethylmethacrylate (PMMA) nanocomposites were fabricated by mixing gold
      nanoparticles capped with oleylamine in polymethylmethacrylate. The samples were
      analysed using UV-vis absorption spectroscopy, transmission electron microscopy,
      small angle x-ray scattering, Fourier transform infrared spectrometry (FTIR) and
      x-ray photoelectron spectroscopy (XPS). Electrical resistivity of nanocomposite
      samples was measured by a four-probe technique in the 70-300 K range. The
      nanocomposites showed a transition with an onset at ~160-165 K. They exhibited a
      semiconductor-like conductivity at higher temperatures and nearly temperature
      independent conductivity at lower temperatures. The interfacial interaction of Au
      nanoparticles and PMMA polymer is investigated using FTIR and XPS. A ligand
      exchange process occurs when capped gold nanoparticles are incorporated in PMMA
      polymer.

PMID- 21727550
TI  - Transport properties of hybrid nanoparticle-nanowire systems and their
      application to gas sensing.
AB  - Experimental data and theoretical modelling of the I-V characteristics of a gas
      sensor constructed from a mat of Au nanoparticle-coated GaN nanowires are
      presented. The principal mechanism for the response of the gas sensor to methane
      is explained in terms of the formation of a depletion layer within the nanowires
      due to the presence of the gold nanoparticles. The depth of the depletion layer
      is modulated by the potential induced by the physisorption of gas molecules onto
      the Au nanoparticles. A statistical model of the temperature-dependent I-V
      characteristics of bare and Au nanoparticle-decorated mats of GaN nanowires based
      on Poisson's equation has been used to determine the depth of the depletion
      layers of the nanowires. The room-temperature carrier concentration for the GaN
      nanowires was determined to be approximately 2.2 * 10(17) cm(-3). The induced
      potential due to methane physisorption onto the Au nanoparticles that decorate
      the GaN nanowires was determined to be approximately -37 mV.

PMID- 21727551
TI  - Synthesis and electronic properties of ferrocene-filled double-walled carbon
      nanotubes.
AB  - Double-walled carbon nanotubes (DWNTs) are filled with ferrocene molecules by a
      vapour diffusion method for the first time. The as-synthesized ferrocene-filled
      DWNTs are characterized by transmission electron microscopy (TEM), energy
      dispersive x-ray spectrometry (EDX) and Raman spectroscopy. Electronic properties
      of double-walled carbon nanotubes (DWNTs) filled with ferrocene molecules are
      studied by fabricating them as the channels of field-effect transistor (FET)
      devices. Our results reveal that electronic properties of ferrocene-filled DWNTs
      are greatly modified due to the charge transfer between ferrocene molecules and
      DWNTs. In addition, after ferrocene molecules are decomposed inside DWNTs,
      electronic properties of DWNTs exhibit a further change due to Fe encapsulation,
      and unipolar n-type semiconducting DWNTs are consequently obtained.

PMID- 21727552
TI  - Transferrin-mediated PEGylated nanoparticles for delivery of DNA/PLL.
AB  - The purpose of this work was to determine the stability of pDNA/poly(L-lysine)
      complex (DNA/PLL) during microencapsulation, prepare transferrin (TF) conjugated
      PEGylated nanoparticles (TF-PEG-NP) loading DNA/PLL, and assess its
      physicochemical characteristics and in vitro transfection efficiency. The DNA/PLL
      was prepared by mixing plasmid DNA (pDNA) in deionized water with various amounts
      of PLL. PEGylated nanoparticles (PEG-NP) loading DNA/PLL were prepared by a water
      oil-water double emulsion solvent evaporation technique. TF-PEG-NP was prepared
      by coupling TF with PEG-NP. The physicochemical characteristics of TF-PEG-NP and
      in vitro transfection efficiency on K562 cells were measured. The results showed
      that free pDNA reserved its double supercoiled form (dsDNA) for only on average
      25.7% after sonification, but over 70% of dsDNA was reserved after pDNA was
      contracted with PLL. The particle size range of TF-PEG-NP loading DNA/PLL was 150
      450 nm with entrapment efficiency over 70%. TF-PEG-NP exhibited the low burst
      effect (<10%) within 1 day. After the first phase, DNA/PLL displayed a sustained
      release. The amount of cumulated DNA/PLL release from TF-PEG-NP with 2% polymer
      over 7 days was 85.4% for DNA/PLL (1:0.3 mass ratio), 59.8% and 43.1% for DNA/PLL
      (1:0.6) and DNA/PLL (1:1.0), respectively. To TF-PEG-NP loading DNA/PLL without
      chloroquine, the percentage of EGFP expressing cells was 28.9% for complexes
      consisting of DNA/PLL (1:0.3), 38.5% and 39.7% for DNA/PLL (1:0.6) and DNA/PLL
      (1:1.0), respectively. In TF-PEG-NP loading DNA/PLL with chloroquine, more cells
      were transfected, the percentage of positive cells was 37.6% (DNA/PLL, 1:0.3),
      47.1% (DNA/PLL, 1:0.6) and 45.8% (DNA/PLL, 1:1.0), which meant that the
      transfection efficiency of pDNA was increased by over 50 times when PLL and TF
      PEG-NP were jointly used as a plasmid DNA carrier, in particular, the maximal
      percentage of positive cells (47.1%) from TF-PEG-NP loading DNA/PLL (1:0.6) was
      about 70 times the transfection efficiency of free plasmid DNA. The average cell
      viability of TF-PEG-NP loading DNA/PLL was about 90%, which meant that TF-PEG-NP
      appeared to be safer than PLL alone. As a result, TF-PEG-NP loading DNA/PLL could
      be a more effective non-viral vector for the delivery of pDNA.

PMID- 21727553
TI  - Synthesis of metallic nanoparticles protected with N,N,N-trimethyl chitosan
      chloride via a relatively weak affinity.
AB  - A water-soluble cationic chitosan derivative, N,N,N-trimethyl chitosan chloride
      (TMC), was synthesized and used as a stabilizing reagent for the synthesis of
      highly stable Au, Ag and Pt nanoparticles in a single-phase of neutral aqueous
      solution. The morphology and stability of metallic nanoparticles were evaluated
      by transmission electron microscopy and UV-vis spectroscopy. The results showed
      that well-dispersed metallic nanoparticles have a spherical morphology with
      diameters of about 3 +/- 0.5 nm. The prepared gold nanoparticles are stable in
      the aqueous solution (no significant changes in their morphology and size within
      10 months) due to repulsion between the charged polymer shell coatings around the
      metallic nanoparticles. The relatively low affinity of TMC on gold nanoparticles
      was confirmed by using a ligand exchange experiment. The mechanism stabilizing
      the chitosan derivative and the neighbouring gold nanoparticles was identified by
      FTIR, (1)H NMR and (13)C NMR measurements.

PMID- 21727554
TI  - Formation of uniform and square nanopore arrays on (100) InP surfaces by a two
      step etching method.
AB  - Uniform and square single-crystal InP nanopore arrays have been successfully
      fabricated on a (100) n-InP surface by a two-step etching method. The
      characteristic of slow etching rates in four equivalent crystalline (011) facets
      of (100) n-InP in a mixture of pure HCl and pure H(3)PO(4) has been found, which
      is the main reason for the formation of square single-crystal InP nanopores. The
      distribution of nanopores can be closely associated with the distribution of
      carriers in the semiconductor during the electrochemical etching process. An
      oscillating behaviour of current has been observed, which can probably be
      attributed to the oscillations in concentration of the electrolyte at the pore
      tips caused by diffusion of the electrolyte in the nanopore channels.

PMID- 21727555
TI  - Silica coated, water dispersible and photoluminescent Y (V,P)O(4):Eu(3+),Bi(3+)
      nanophosphors.
AB  - We propose an approach for silica encapsulation of YV((0.7))P((0.3))O(4):Eu(3+),
      Bi(3+) nanophosphors through a microemulsion process. The resulting
      YV((0.7))P((0.3))O(4):Eu(3+), Bi(3+)@SiO(2) core-shell nanophosphors were
      characterized by transmission electron microscopy, UV/vis absorption and
      photoluminescence spectroscopy, energy-dispersive x-ray analysis (EDAX), selected
      area electron diffraction and zeta-potential measurements. The obtained
      nanocomposites have quite a uniform spherical shape and diameters of about 15 nm.
      Zeta-potential measurements show that coated particles are stable at high volume
      fractions and can endure large variations in pH and electrolyte concentration
      without coalescence. These core-shell nanophosphors could also be used as
      ultrasensitive biological labels, because they are obtained in nanoscale and well
      dispersible in water.

PMID- 21727556
TI  - Aqueous nickel-nitrilotriacetate modified Fe(3)O(4)-NH(3)(+) nanoparticles for
      protein purification and cell targeting.
AB  - A comprehensive totally aqueous phase synthesis of nickel-nitrilotriacetate (Ni
      NTA) modified superparamagnetic Fe(3)O(4) nanoparticles is presented. The
      Fe(3)O(4)-NTA-Ni nanoparticles are able to perform efficient and specific
      purification of 6-His tagged proteins from crude cell lysates, as evidenced by
      sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western
      blot analysis. The average binding capacity, as demonstrated by streptopain (M(W)
      42 kDa), is 0.23 mg/mg (protein/Fe(3)O(4)-NTA-Ni). Considering the high affinity
      and specificity of the binding between hexahistidine motif and Ni-NTA, Ni-NTA
      modified nanoparticles could act as a module to carry 6-His tagged proteins on
      the particle surface with molecular orientation control, since only the 6-His
      domain could be attached. These modularly designed functional nanoparticles
      enhance cancer cell targeting, as supported by the in vitro receptor mediated
      targeting assay using RGD-4C-6-His fusion peptide. The nanoparticles show no
      significant hemolysis for human blood and could be investigated further for their
      in vivo functional imaging applications.

PMID- 21727557
TI  - Detection of magnetic nanoparticles in tissue using magneto-motive ultrasound.
AB  - The purpose of this study was to demonstrate the magneto-motive ultrasonic
      detection of superparamagnetic iron oxide (SPIO) nanoparticles as a marker of
      macrophage recruitment in tissue. The capability of ultrasound to detect SPIO
      nanoparticles (core diameter ~20 nm) taken up by murine liver macrophages was
      investigated. Eight mice were sacrificed two days after the intravenous
      administration of four SPIO doses (1.5, 1.0, 0.5, and 0.1 mmol Fe/kg body
      weight). In the iron-laden livers, ultrasound Doppler measurements showed a
      frequency shift in response to an applied time-varying magnetic field. M-mode
      scan and colour power Doppler images of the iron-laden livers also demonstrated
      nanoparticle movement under focused magnetic field excitation. In the livers of
      two saline injected control mice, no movement was observed using any ultrasound
      imaging modes. The results of our experiments indicate that ultrasound imaging of
      magneto-motive excitation is a candidate imaging modality to identify tissue
      based macrophages containing SPIO nanoparticles.

PMID- 21727558
TI  - Morphology-controllable fabrication of ordered platinum nanoshells with reduced
      symmetry.
AB  - This paper presents a novel method for fabricating an ordered array of metallic
      nanoshells with a controllable shape by a combination of a porous polymer
      template and a nanocrystal-seeded electroless plating technique. The morphology
      of hollow particles has a strong dependence on the seed-deposition time onto the
      surfaces of the original colloidal template. Using this method, ordered Pt
      nanobowls (bowl-shaped shells) and, alternatively, nanocups (cup-shaped shells)
      are prepared. These materials show some intriguing properties: (i) reduced
      symmetry of the building blocks; (ii) a well-ordered structure; and (iii) a high
      ratio of surface area to volume, all of which are useful in many areas such as
      catalysts, sensors, and photonic crystals.

PMID- 21727559
TI  - Ni(3)Si(Al)/a-SiO(x) core-shell nanoparticles: characterization, shell formation,
      and stability.
AB  - We have used an electrochemical selective phase dissolution method to extract
      nanoprecipitates of the Ni(3)Si-type intermetallic phase from two-phase Ni-Si and
      Ni-Si-Al alloys by dissolving the matrix phase. The extracted nanoparticles are
      characterized by transmission electron microscopy, energy-dispersive x-ray
      spectrometry, x-ray powder diffraction, and electron powder diffraction. It is
      found that the Ni(3)Si-type nanoparticles have a core-shell structure. The core
      maintains the size, the shape, and the crystal structure of the precipitates that
      existed in the bulk alloys, while the shell is an amorphous phase, containing
      only Si and O (SiO(x)). The shell forms around the precipitates during the
      extraction process. After annealing the nanoparticles in nitrogen at 700  degrees
      C, the tridymite phase recrystallizes within the shell, which remains partially
      amorphous. In contrast, on annealing in air at 1000  degrees C, no changes in the
      composition or the structure of the nanoparticles occur. It is suggested that the
      shell forms after dealloying of the matrix phase, where Si atoms, the main
      constituents of the shell, migrate to the surface of the precipitates.

PMID- 21727560
TI  - Mapping van der Waals forces with frequency modulation dynamic force microscopy.
AB  - Nanometre-size gold clusters supported on MoS(2)(0001) are investigated by means
      of ultrahigh-vacuum frequency modulation dynamic force microscopy. Topography and
      frequency shift images are simultaneously obtained using the average tunnelling
      current to regulate the tip-substrate distance. Two families of clusters are
      observed, giving different frequency shift images. While the topographic and
      frequency shift profiles have similar shapes on small clusters (size [Formula:
      see text] nm), they are quite different near the top of large clusters (size
      [Formula: see text] nm): the topographic profile is rounded, but the frequency
      shift profile exhibits rather steep edges and a depression near the centre of the
      island. It is demonstrated that these differences result from the finite range of
      van der Waals forces. On small islands, the frequency shift is dominated by the
      interaction of the tip with the substrate. On large islands, it is dominated by
      the interaction with the island. The particular observed shape results from the
      geometry of the island. These interpretations are comforted by analytical and
      numerical calculations. In particular, the characteristic shape of the frequency
      shift profiles on large islands can be reproduced by introducing realistic
      parameters and considering only the contribution of van der Waals forces.

PMID- 21727561
TI  - In situ electrostatic assembly of CdS nanoparticles onto aligned multiwalled
      carbon nanotubes in aqueous solution.
AB  - A simple method is described for the electrostatic assembly of CdS nanoparticles
      onto oxidized aligned multiwalled carbon nanotubes (MWCNTs) in aqueous solution.
      The method is convenient to control and allows the formation of a stable, water
      soluble suspension of CdS/aligned-MWCNT heterostructures. The prepared
      CdS/aligned-MWCNT heterostructures are characterized by transmission electron
      microscopy (TEM), high-resolution TEM (HRTEM), energy dispersive x-ray
      spectroscopy (EDS), x-ray diffraction (XRD) and Fourier transform infrared
      spectrometry (FT-IR). The fluorescence and UV absorption spectral properties of
      the hybrid material demonstrate electron transfer from CdS nanoparticles to
      aligned-MWCNTs, which implies its potential applications in photovoltaic cells,
      photocatalysis, and solar energy conversion.

PMID- 21727562
TI  - Facile sonochemical synthesis of CePO(4):Tb/LaPO(4) core/shell nanorods with
      highly improved photoluminescent properties.
AB  - A simple, efficient and quick method has been established for the synthesis of
      CePO(4):Tb nanorods and CePO(4):Tb/LaPO(4) core/shell nanorods via ultrasound
      irradiation of inorganic salt aqueous solution under ambient conditions for 2 h.
      The as-prepared products were characterized by means of powder x-ray diffraction
      (PXRD), transmission electron microscopy (TEM), high-resolution transmission
      electron microscopy (HRTEM), selected area electron diffraction (SAED), x-ray
      photoelectron spectroscopy (XPS), photoluminescence (PL) spectra and lifetimes.
      TEM micrographs show that all of the as-prepared cerium phosphate products have
      rod-like shape, and have a relatively high degree of crystallinity and
      uniformity. HRTEM micrographs and SAED results prove that these nanorods are
      single crystalline in nature. The emission intensity and lifetime of the
      CePO(4):Tb/LaPO(4) core/shell nanorods increased significantly with respect to
      those of CePO(4):Tb core nanorods under the same conditions. A substantial
      reduction in reaction time as well as reaction temperature is observed compared
      with the hydrothermal process.

PMID- 21727563
TI  - Self-assembly of charged microclusters of CdSe/ZnS core/shell nanodots and
      nanorods into hierarchically ordered colloidal arrays.
AB  - A thermodynamically driven self-organization of microclusters of semiconductor
      nanocrystals with a narrow size distribution into periodic two-dimensional (2D)
      arrays is an attractive low-cost technique for the fabrication of 2D photonic
      crystals. We have found that CdSe/ZnS core/shell quantum dots or quantum rods,
      transferred in aqueous phase after capping with the bifunctional surface-active
      agent DL-cysteine, form on a poly-L-lysine coated surface homogeneously sized
      micro-particles, droplet-like spheroid clusters and hexagon-like colloidal
      crystals self-organized into millimetre-sized 2D hexagonal assemblies. The
      presence of an organic molecular layer around the micro-particles prevents
      immediate contact between them, forming an interstitial space which may be varied
      in thickness by changing the origin of the molecular layer capping nanocrystals.
      Due to the high refractive index of CdSe and the low refractive index of the
      interstitial spaces, these structures are expected to have deep gaps in their
      photonic band, forming hierarchically ordered 2D arrays of potentially photonic
      materials.

PMID- 21727564
TI  - Robust nanopatterning by laser-induced dewetting of metal nanofilms.
AB  - We have observed nanopattern formation with robust and controllable spatial
      ordering by laser-induced dewetting in nanoscopic metal films. Pattern evolution
      in Co film of thickness 1<=h<=8 nm on SiO(2) was achieved under multiple pulse
      irradiation using a 9 ns pulse laser. Dewetting leads to the formation of
      cellular patterns which evolve into polygons that eventually break up into
      nanoparticles with unimodal size distribution and short range ordering in nearest
      neighbour spacing R. Spatial ordering was attributed to a hydrodynamic thin film
      instability and resulted in a predictable variation of R and particle diameter D
      with h. The length scales R and D were found to be independent of the laser
      energy. These results suggest that spatially ordered metal nanoparticles can be
      robustly assembled by laser-induced dewetting.

PMID- 21727565
TI  - Highly resolved non-contact atomic force microscopy images of the Sn/Si(111)
      ([Formula: see text]) surface.
AB  - The Sn/Si(111)-([Formula: see text]) surface is observed by using non-contact
      atomic force microscopy (NC-AFM) at room temperature. The images at relatively
      far tip-surface distances show four protrusions in each ([Formula: see text])
      unit cell, which are similar to previously reported scanning tunnelling
      microscopy (STM) images. On the other hand, it is found that, at closer tip
      surface distances, eight protrusions are clearly resolved, which indicates that
      the spatial resolution of NC-AFM is higher than that of STM as far as imaging
      this surface is concerned. Our high-resolution NC-AFM images are in good
      agreement with a recently proposed model based on 13 Sn atoms per unit cell.

PMID- 21727566
TI  - Bennett clocking of quantum-dot cellular automata and the limits to binary logic
      scaling.
AB  - We examine power dissipation in different clocking schemes for molecular quantum
      dot cellular automata (QCA) circuits. 'Landauer clocking' involves the adiabatic
      transition of a molecular cell from the null state to an active state carrying
      data. Cell layout creates devices which allow data in cells to interact and
      thereby perform useful computation. We perform direct solutions of the equation
      of motion for the system in contact with the thermal environment and see that
      Landauer's Principle applies: one must dissipate an energy of at least k(B)T per
      bit only when the information is erased. The ideas of Bennett can be applied to
      keep copies of the bit information by echoing inputs to outputs, thus embedding
      any logically irreversible circuit in a logically reversible circuit, at the cost
      of added circuit complexity. A promising alternative which we term 'Bennett
      clocking' requires only altering the timing of the clocking signals so that bit
      information is simply held in place by the clock until a computational block is
      complete, then erased in the reverse order of computation. This approach results
      in ultralow power dissipation without additional circuit complexity. These
      results offer a concrete example in which to consider recent claims regarding the
      fundamental limits of binary logic scaling.

PMID- 21727567
TI  - Microstructure and superconductivity of highly ordered YBa(2)Cu(3)O(7-delta)
      nanowire arrays.
AB  - In order to explore the fundamental properties of one-dimensional nanostructured
      high-temperature superconductors and enhance their promising applications, a
      universal and general method for the synthesis of high-quality YBa(2)Cu(3)O(7
      delta) (YBCO) nanowire arrays is developed, which involves the combination of a
      novel sol-gel process to lower the crystallization temperature of YBCO, and
      porous anodic alumina (PAA) as an effective morphology-directing hard template.
      Field-emission scanning electron microscopy (FE-SEM) and transmission electron
      microscopy (TEM) results indicate that the as-prepared YBCO nanowires have
      average diameters of about 50 nm and lengths up to several microns. The
      structures of the samples were analysed by x-ray diffraction (XRD), high
      resolution transmission electron microscopy (HRTEM), energy-dispersive x-ray
      spectroscopy (EDX) and inductively coupled plasma (ICP) analysis, which indicate
      that the nanowires are well crystallized with orthorhombic YBCO-123 structure.
      The magnetization measurement under zero-field-cooled (ZFC) mode indicates that
      the superconducting transition temperature (T(c)) of the nanowires is about 92 K,
      which is in agreement with that of a bulk YBCO sample.

PMID- 21727568
TI  - Solid solubility limit in alloying nanoparticles.
AB  - In order to gain a better thermodynamic understanding of the phase diagram of
      alloying nanoparticles, we establish a size-dependent solid solubility model of
      binary metallic systems to elucidate the anomalous solid solubility in nanometre
      sized alloying particles. It is found that a diameter of 20 nm seems a threshold
      value of the size of alloying nanoparticles for the unusual solid solubility,
      i.e. the solubility is greatly promoted with decreasing grain size when the size
      of alloying nanoparticles is less than 20 nm. Taking the Pb-Sn system as an
      example, we show that the theoretical predictions are consistent with
      experimental data.

PMID- 21727569
TI  - Fractionation of SWNT/nucleic acid complexes by agarose gel electrophoresis.
AB  - We show that aqueous dispersions of single-walled carbon nanotubes (SWNTs),
      prepared with the aid of nucleic acids (NAs) such as RNA or DNA, can be separated
      into fractions using agarose gel electrophoresis. In a DC electric field, SWNT/NA
      complexes migrate in the gel in the direction of positive potential to form well
      defined bands. Raman spectroscopy as a function of band position shows that
      nanotubes having different spectroscopic properties possess different
      electrophoretic mobilities. The migration patterns for SWNT/RNA and SWNT/DNA
      complexes differ. Parallel elution of the SWNT/NA complexes from the gel during
      electrophoresis and subsequent characterization by AFM reveals differences in
      nanotube diameter, length and curvature. The results suggest that fractionation
      of nanotubes can be achieved by this procedure. We discuss factors affecting the
      mobility of the nanotube complexes and propose analytical applications of this
      technique.

PMID- 21727570
TI  - The effect of Mn doping in FePt nanoparticles on the magnetic properties of the
      L1(0) phase.
AB  - FePtMn nanoparticles with a narrow size distribution and an average diameter of 3
      nm were synthesized by the chemical reduction of Fe(acac)(3) and Pt(acac)(2) by
      NaBH(4) and the thermal decomposition of Mn(2)(CO)(10) in phenyl ether. The as
      made nanoparticles have a disordered face-centred cubic (fcc) structure, which
      transformed after thermal treatment at 650  degrees C to an ordered face-centred
      tetragonal (fct) structure, possessing coercivity values up to 13.7 kOe at room
      temperature. The coercivity of the annealed samples depends on the amount of Mn
      added to the reaction mixture, with the coercive field increasing significantly
      with the partial substitution of Pt by Mn, while the partial substitution of Fe
      by Mn does not affect the magnetic properties strongly.

PMID- 21727571
TI  - Enhancement of optical nonlinearity in periodic gold nanoparticle arrays.
AB  - Linear and nonlinear optical properties of periodic triangular Au nanoparticle
      arrays were investigated. We compared the optical nonlinearity of periodic Au
      nanoparticle arrays with that of the ultra-thin gold film consisting of randomly
      distributed spheroidal clusters. A pronounced enhancement of the third-order
      nonlinear optical susceptibility chi((3)) in Au arrays was observed, and the
      figure of merit, chi((3))/alpha, of the periodic nanoparticle arrays is one order
      of magnitude larger than that of the ultra-thin film. Such an enhancement of the
      optical nonlinearity could be due to the strong local field near the triangular
      nanoparticles.

PMID- 21727572
TI  - One-step synthesis of spherical alpha-Ni(OH)(2) nanoarchitectures.
AB  - We report the synthesis of sphere-like alpha-Ni(OH)(2) nanoarchitecture by self
      assembly with the aid of hexamethylenetetramine (HMT). The alpha-Ni(OH)(2)
      nanoarchitectures, with a diameter of several micrometres, are composed of many
      nanoflakelets about 10 nm in thickness. The influences of the reaction
      temperature, time, reagent, nickel salt and pH value on the morphology and
      structure of the alpha-Ni(OH)(2) were studied, the chemical and thermal stability
      are discussed, and the formation mechanism is proposed. The alpha-Ni(OH)(2)
      nanoarchitectures display a good electrochemical capacity.

PMID- 21727573
TI  - Drying induced upright sliding and reorganization of carbon nanotube arrays.
AB  - Driven by capillary force, wet carbon nanotube (CNT) arrays have been found to
      reorganize into cellular structures upon drying. During the reorganization
      process, individual CNTs are firmly attached to the substrate and have to lie
      down on the substrate at cell bottoms, forming closed cells. Here we demonstrate
      that by modifying catalyst structures, the adhesion of CNTs to the substrate can
      be weakened. Upon drying such CNT arrays, CNTs may slide away from their original
      sites on the surface and self-assemble into cellular patterns with bottoms open.
      It is also found that the sliding distance of CNTs increases with array height,
      and drying millimetre tall arrays leads to the sliding of CNTs over a few hundred
      micrometres and the eventual self-assembly into discrete islands. By introducing
      regular vacancies in CNT arrays, CNTs may be manipulated into different patterns.

PMID- 21727574
TI  - Reduced-temperature ethanol sensing characteristics of flower-like ZnO nanorods
      synthesized by a sonochemical method.
AB  - Flower-like ZnO nanorods with diameters less than 15 nm were synthesized by a
      sonochemical method. The sensors fabricated from the nanorods exhibited excellent
      ethanol sensing properties. At the working temperature of 300  degrees C, their
      sensitivity was 176.8-100 ppm ethanol vapour. While the working temperature was
      reduced to 140  degrees C, they were still able to detect ethanol vapour at the
      ppm level. The reduced working temperature may be attributed to the small sizes
      of the nanorods.

PMID- 21727575
TI  - Growth of carbon nanotubes on cobalt catalyst film using electron cyclotron
      resonance chemical vapour deposition without thermal heating.
AB  - This paper demonstrates that carbon nanotubes (CNTs) can be synthesized on a
      cobalt coated silicon substrate using electron cyclotron chemical vapour
      deposition and without intentionally heating the substrate. With the mixed gases
      of C(3)H(8)/N(2), CNTs with a multi-walled structure and a diameter up to 70 nm
      have been observed. Results show that the diameter of the CNTs increases with the
      thickness of the cobalt catalyst film and the amount of nitrogen incorporated in
      the CNT films considerably influences the structures of the CNTs. Vertically
      aligned CNTs can be fabricated with a microwave power as low as 300 W and the
      flow rate ratio of C(3)H(8)/N(2) = 20/20 sccm. The CNTs exhibit a turn-on field
      of 0.2 V um(-1) determined at the emission current density of 10 uA cm(-2).

PMID- 21727576
TI  - The effect of Ge implantation dose on the optical properties of Ge nanocrystals
      in SiO(2).
AB  - Ge nanocrystallites (Ge-nc) embedded in a SiO(2) matrix are investigated using
      Raman spectroscopy, photoluminescence and Fourier transform infrared
      spectroscopy. The samples were prepared by ion implantation with different
      implantation doses (0.5, 0.8, 1, 2, 3 and 4) * 10(16) cm(-2) using 250 keV
      energy. After implantation, the samples were annealed at 1000  degrees C in a
      forming gas atmosphere for 1 h. All samples show a broad Raman spectrum centred
      at w~304 cm(-1) with a slight shift depending on the implantation doses. The
      Raman intensity also depends on the Ge(74+) dose. A maximum photoluminescence
      intensity is observed for the sample implanted at room temperature with a dose of
      2 * 10(16) cm(-2) at 3.2 eV. Infrared spectroscopy shows that the SiO(2) films
      moved off stoichiometry due to Ge(74+) ion implantation, and Ge oxides are formed
      in it. This result is shown as a reduction of GeO(x) at exactly the dose
      corresponding to the maximum blue-violet PL emission and the largest Raman
      emission at 304 cm(-1). Finally, the Raman spectra were fitted with a theoretical
      expression to evaluate the average size, full-width at half-maximum (FWHM) and
      dispersion of Ge-nc size.

PMID- 21727577
TI  - Preparation of photosensitized nanocrystalline TiO(2) hydrosol by nanosized CdS
      at low temperature.
AB  - A new method was developed for the fabrication of CdS-TiO(2) semiconductor
      nanoparticles as visible-light-excitable photocatalyst at low temperatures.
      Nanosized CdS acting as an effective and stable sensitizer was incorporated into
      TiO(2) by microemulsion-mediated solvothermal hydrolyzation followed by acidic
      peptization of the precipitate under 70  degrees C. The new method avoided the
      calcination or other pyrochemical treatments involved in traditional
      preparations, and thus eliminated the unwanted agglomeration of nanoparticles or
      the oxidation of CdS by oxygen. Compared to traditional methods, it was highly
      simplified, bypassing those miscellaneous steps like filtration, sintering,
      milling and redispersion in solutions. The crystal structure, configuration,
      element composition, as well as the light-absorption properties of the obtained
      CdS-TiO(2) hydrosol were characterized in detail. The hydrosol consisting of
      uniform and small crystalline particles of about 2 nm in diameter was
      thermodynamically stable and showed good dispersibility. The photocatalytic
      activity of the 'coupled' material was confirmed through the photocatalytic
      degradation of methylene blue (MB) dye under visible light irradiation, and the
      cooperative photocatalytic mechanism is discussed.

PMID- 21727578
TI  - Photoelectric response mechanisms dependent on RuN3 and CuPc sensitized ZnO
      nanoparticles to oxygen gas.
AB  - ZnO nanoparticles were synthesized by a simple mild solution method. Spectral
      sensitization of nanocrystalline ZnO was carried out with [Ru(dcbpy)(2)(NCS)(2)
      (dcbyp = 2,2'-bipyridyl-4,4'-dicarboxylate)] (RuN3) and CuPc. The electron
      transfer behaviours at the surface and interface in ZnO/RuN3 and ZnO/CuPc were
      investigated using a surface photocurrent technique. When exposed to oxygen gas,
      the surface photocurrent (I(SPC)) responses of ZnO/RuN3 and ZnO/CuPc decreased
      and increased, respectively. The results demonstrated through the adsorption of
      oxygen gas that there are different microscopic mechanisms for the surface
      charges. The microscopic processes of electron transfer between oxygen molecules
      and dye-sensitized ZnO are discussed in detail in this paper. Such research
      should be valuable for fundamental science and optoelectronic device application
      of ZnO nanoparticles.

PMID- 21727579
TI  - Cross-talk compensation of hyperfine control in donor-qubit architectures.
AB  - We theoretically investigate cross-talk in hyperfine gate control of donor-qubit
      quantum computer architectures, in particular the Kane proposal. By solving the
      Poisson and Schrodinger equations numerically for the gated donor system, we
      calculate the change in hyperfine coupling and thus the error in spin-rotation
      for the donor nuclear-electron spin system, as the gate-donor distance is varied.
      We thus determine the effect of cross-talk-the inadvertent effect on non-target
      neighbouring qubits-which occurs due to closeness of the control gates (20-30
      nm). The use of compensation protocols is investigated, whereby the extent of
      cross-talk is limited by the application of compensation bias to a series of
      gates. In the light of these factors, architectural implications are then
      considered.

PMID- 21727580
TI  - Nanoscale capacitance imaging with attofarad resolution using ac current sensing
      atomic force microscopy.
AB  - Nanoscale capacitance imaging with attofarad resolution (~1 aF) of a nano
      structured oxide thin film, using ac current sensing atomic force microscopy, is
      reported. Capacitance images are shown to follow the topographic profile of the
      oxide closely, with nanometre vertical resolution. A comparison between
      experimental data and theoretical models shows that the capacitance variations
      observed in the measurements can be mainly associated with the capacitance probed
      by the tip apex and not with positional changes of stray capacitance
      contributions. Capacitance versus distance measurements further support this
      conclusion. The application of this technique to the characterization of samples
      with non-voltage-dependent capacitance, such as very thin dielectric films, self
      assembled monolayers and biological membranes, can provide new insight into the
      dielectric properties at the nanoscale.

PMID- 21727581
TI  - Optical evidence for reactive processes when embedding Cu nanoparticles in
      Al(2)O(3) by pulsed laser deposition.
AB  - The optical response of nanocomposite thin films formed by Cu nanoparticles (NPs)
      embedded in amorphous aluminium oxide (Al(2)O(3)) prepared by pulsed laser
      deposition (PLD) in vacuum is studied in order to investigate the possible
      existence of reactive processes on the Cu NPs during their covering with
      Al(2)O(3). The study is performed as a function of the laser fluence on the
      Al(2)O(3) target (0.6-4.6 J cm(-2)), while the laser fluence for Cu ablation is
      kept constant (1.8 J cm(-2)). The structural analysis of the films shows that
      they are formed by a high density of NPs with average dimensions in the 4.9-5.9
      nm range. The optical response of the films has been followed in situ by real
      time reflectivity measurements at 633 nm and after deposition by transmission
      measurements as a function of wavelength around the surface plasmon resonance
      (SPR). For low laser fluences on the Al(2)O(3) target, the absorption spectrum is
      dominated by a well-defined SPR absorption band at 1.9 eV. As the laser fluence
      is increased, the intensity of the absorption band associated with the SPR
      decreases and shifts to 2.1 eV. The films deposited at low fluences contain
      metallic Cu NPs and, as the laser fluence increases sputtering of Cu from the NPs
      and mixing of the species from the Al(2)O(3) deposition with the Cu from the NPs
      surface takes place. The latter process leads to the formation of an Al-Cu oxide
      cover on the Cu NPs. The present results provide evidence for mixing of species
      from the host and Cu at the surface of the NPs, and it is shown how the degree of
      mixing depends on the laser fluence used to ablate the Al(2)O(3) host target.

PMID- 21727582
TI  - Design at the nanometre scale of multifunctional materials using supercritical
      fluid chemical deposition.
AB  - Recent developments in multifunctional devices show the interest in combining
      different materials to obtain specific properties. Through supercritical fluid
      chemical deposition (SFCD), silica spheres, used as a model support, were coated
      with copper nanoparticles (5-17 nm) with a tuneable amount of coverage (40-80%).
      The coating process is based on the reduction of metal precursors with hydrogen
      in a supercritical CO(2)/isopropanol mixture in a temperature range between 100
      and 150  degrees C at 24 MPa. Several parameters were studied such as
      temperature, residence time or mass ratio of precursor/silica spheres, allowing
      control of the size of the copper nanoparticles and of the amount of coverage
      from metal nanoparticles scattered onto the surface to a metal nanoparticle thin
      film.

PMID- 21727583
TI  - Tuning the absorptions of Au nanospheres on a microshell by photo-deformation.
AB  - We report the design, modelling, fabrication, and testing of a photo-tunable
      particulate medium that comprises photo-responsible polymeric microshells covered
      by Au nanospheres. The microshells were formed by a layer-by-layer method. The
      charged Au nanospheres were coated on outer surfaces of the microshells. The
      polymeric shells contain azobenzene moieties and shrink upon ultraviolet
      irradiation; therefore, the interparticle spaces between the nanospheres are
      tunable by UV light. The absorption spectrum of the Au nanosphere modified
      microshells changed drastically after the shrinkage. A decreased absorption peak
      of Au nanospheres and an enhanced absorption in the near-infrared region were
      clearly observed. The results of theoretical modelling suggest that the overall
      spectral changes stem mainly from the enhanced particle interactions and also
      from the field enhancements in the space among the nanospheres.

PMID- 21727584
TI  - Selective growth of silica nanowires in silicon catalysed by Pt thin film.
AB  - Selective growth of amorphous silica nanowires on a silicon wafer deposited with
      Pt thin film is reported. The mechanism of nanowire growth has been established
      to follow the vapour liquid solid (VLS) model via the PtSi phase acting as the
      catalyst. Nanowires grow with diameters ranging from 50 to 500 nm. These bottom
      up grown nanowires exhibit photoluminescence with a stable emission of blue light
      at 430 nm under excitation. The effect of varying the seed layer thickness (Pt
      film) from 2 to 100 nm has been studied. It is observed that, above 10 nm
      thickness, a continuous layer of Pt(2)Si re-solidifies on the surface, inhibiting
      the growth of nanowires. The selectivity to the Pt thickness has been exploited
      to create regions of nanowires connected to conducting silicide (Pt(2)Si)
      simultaneously in a single furnace treatment. This novel approach has opened the
      gateways for realizing hybrid interconnects in silicon for various nano-optical
      applications such as the localization of light, low-dimensional waveguides for
      functional microphotonics, scanning near-field microscopy, and nanoantennae.

PMID- 21727585
TI  - Fabrication of a nanocrystalline Ni-Co/CoO functionally graded layer with
      excellent electrochemical corrosion and tribological performance.
AB  - Nanocrystalline (NC) Ni-Co/CoO functionally graded materials with excellent
      lubricating, high anti-corrosion and anti-wear performance were fabricated by
      electrodeposition and subsequent cyclic thermal oxidation and quenching.
      Transmission electron microscopy and energy dispersive x-ray spectroscopy
      investigations show that bulk Ni-Co gradient deposits with an average grain size
      in the range of 13-40 nm demonstrated a graded structure transition from face
      centred cubic to hexagonal close packed and graded composition changes from Ni
      rich to Co-rich regions with the increase in deposit thickness. X-ray diffraction
      and x-ray photoelectron spectroscopy analysis indicated the surface layer of NC
      Ni-Co graded materials to be mainly composed of dense and ultrafine CoO with a
      (111) preferred orientation. The NC Ni-Co/CoO functionally graded materials
      exhibited significantly enhanced corrosion resistance in both NaOH and NaCl
      solutions and remarkably improved wear resistance and dry self-lubricating
      performance when compared with the NC Ni and Ni-Co graded deposits under dry
      sliding wear conditions. The higher corrosion and tribological performance of NC
      Ni-Co/CoO graded materials can be attributed to the graded microstructure within
      the deposits, the anti-corrosion barrier of a dense oxide layer and the solid
      lubrication effect of CoO-rich tribo-surface films.

PMID- 21727586
TI  - Charge-induced strains in single-walled carbon nanotubes.
AB  - This paper investigates the electromechanical coupling in single-walled carbon
      nanotubes. In the model system, the extra electric charge of the nanotube is
      assumed to be uniformly distributed on carbon atoms. The electrostatic
      interactions between charged carbon atoms are calculated using the Coulomb law.
      The deformation of the charged nanotube is obtained by using the molecular
      structural mechanics method and considering the electrostatic interactions as an
      external loading acting on carbon atoms. The axial strain is found to be a
      symmetric function of applied charge, and our predictions are in very good
      agreement with those from ab initio calculations. The present results indicate
      that the nanotube aspect ratio has a strong effect on the axial strain when the
      ratio is less than 10 and the general trend is that the strain increases with the
      aspect ratio. The peak axial and radial strains occur at nanotube diameters of
      around 1.2-1.5 nm.

PMID- 21727587
TI  - Synthesis of carbon nanofibres from a liquid solution containing both catalyst
      and polyethylene glycol.
AB  - Carbon nanofibres (CNFs) exhibiting bamboo-like, hollow fibril morphology were
      prepared from a mixture of polyethylene glycol (PEG) and iron-based compounds
      such as Fe(2)(SO(4))(3).nH(2)O, Fe(NO(3)).9H(2)O or FeO(OH) by a thermal process.
      These materials were well mixed in distilled water prior to thermal treatment in
      an air/nitrogen atmosphere. With increasing temperature, the mixture underwent
      solvent removal, dehydrogenation, thermal decomposition, carbonization and
      catalytic graphitization to form CNFs. Results show that CNFs can be formed with
      different PEG/catalyst ratios (100/1-1000/1 by weight) at 750  degrees C. The
      catalyst effect is discussed for the formation of bamboo-like CNFs. The diameter
      of the CNFs was about 30-50 nm while the length was a few micrometres.

PMID- 21727588
TI  - Micromachined silicon transmission electron microscopy grids for direct
      characterization of as-grown nanotubes.
AB  - Transmission electron microscopy (TEM) is a key technique in the structural
      characterization of carbon nanotubes. For device applications, carbon nanotubes
      are typically grown by chemical vapour deposition (CVD) on silicon substrates.
      However, TEM requires very thin samples, which are electron transparent.
      Therefore, for TEM analysis, CVD grown nanotubes are typically deposited on
      commercial TEM grids by post-processing. However, this procedure can damage the
      nanotubes, and it does not work reliably if the nanotube density is too low. The
      ability to do TEM directly on as-grown nanotubes on the silicon substrate would
      solve these problems. For this purpose, we have fabricated micromachined silicon
      TEM grids with narrow open slits on them. Since the nanotubes grown on these
      substrates are suspended freely over the open slits, the micromachined substrates
      form a natural TEM grid for direct imaging of CVD grown nanotubes. Furthermore,
      the background noise is significantly reduced during micro-Raman spectroscopy,
      resulting in a better signal-to-noise ratio. As a result, these micromachined Si
      substrates provide a low cost, mass producible, efficient, and reliable platform
      for direct TEM, SEM, AFM, and Raman characterization of as-grown nanotubes. These
      grids can be used for characterizing a wide range of other nanomaterials,
      including peapods, nanowires, and nanofibres.

PMID- 21727589
TI  - Self-assembled Al(x)Ga(1-x)N nanorods grown on Si(001) substrates by using plasma
      assisted molecular beam epitaxy.
AB  - Hexagonal Al(x)Ga(1-x)N nanorods were grown by plasma-assisted molecular beam
      epitaxy (PAMBE) on Si(001) substrates. The Al mole fraction was determined from x
      ray diffraction (XRD) measurement and its value was varied from 0 to 15. It is
      found that, under group III-rich conditions, the growth rate of the Al(x)Ga(1-x)N
      nanorods decreases and the diameter increases due to the possibility of
      incorporation of aluminium and gallium. In order to study structural and optical
      properties, x-ray diffraction and cathodoluminescence (CL) measurements were
      carried out. The Al content (x) is calculated from these measurements and their
      values are compared.

PMID- 21727590
TI  - Fabrication, structural characterization and photoluminescence of single-crystal
      Zn(x)Cd(1-x)S zigzag nanowires.
AB  - Large-scale synthesis of ternary Zn(x)Cd(1-x)S zigzag nanowires was achieved in a
      one-step metal-organic chemical vapour deposition (MOCVD) process with co-fed
      single precursors of ZnS and CdS. Their morphologies, structures and optical
      properties were characterized and confirmed by scanning electron microscopy, high
      resolution transmission electron microscopy, x-ray spectroscopy, and
      photoluminescence. The Zn(x)Cd(1-x)S zigzag nanowires are single crystalline,
      with axis [001], by changing the growth direction from [Formula: see text] to
      [Formula: see text]. Regarding the formation of zigzag nanowires, we suggest that
      the shear strain and slight fluctuation of the reaction conditions may be the
      major factors that make the nanowires change growth direction. In addition,
      because of the lower temperature and versatility, this new fabrication method
      might present a new and facile way to form other ternary nanomaterials.
      Furthermore, the green emission of the nanowires may have potential applications
      in electronic/optical nanodevices.

PMID- 21727591
TI  - Improved photoluminescence of silicon nanocrystals in silicon nitride prepared by
      ammonia sputtering.
AB  - In the present work we investigated the photoluminescence property of silicon
      nanocrystals in silicon nitride prepared by ammonia sputtering. Silicon
      nanocrystals were demonstrated to form even after thermal annealing at 700 
      degrees C. Compared with the control sample using N(2) as the reactive gas, the
      luminescence intensity of silicon nanocrystals in silicon nitride prepared by
      NH(3) sputtering was greatly increased. The improvement in photoluminescence was
      attributed to the introduction of hydrogen-related bonds, which could well
      passivate the nonradiative defects existing at the interface between silicon
      nanocrystals and the silicon nitride matrix.

PMID- 21727592
TI  - Modelling of C(2) addition route to the formation of C(60).
AB  - To understand the phenomenon of fullerene growth during its synthesis, an attempt
      is made to model a minimum energy growth route using a semi-empirical quantum
      mechanics code. C(2) addition leading to C(60) was modelled and three main
      routes, i.e. cyclic ring growth, pentagon and fullerene road, were studied. The
      growth starts with linear chains and, at n = 10, ring structures begins to
      dominate. The rings continue to grow and, at some point n>30, they transform into
      close-cage fullerenes and the growth is shown to progress by the fullerene road
      until C(60) is formed. The computer simulations predict a transition from a C(38)
      ring to fullerene. Other growth mechanisms could also occur in the energetic
      environment commonly encountered in fullerene synthesis, but our purpose was to
      identify a minimal energy route which is the most probable structure. Our results
      also indicate that, at n = 20, the corannulene structure is energetically more
      stable than the corresponding fullerene and graphene sheet, however a ring
      structure has lower energy among all the structures up to n<=40. Additionally, we
      have also proved that the fullerene road is energetically more favoured than the
      pentagon road. The overall growth leading to cage closure for n = 60 may not
      occur by a single route but by a combination of more than one route.

PMID- 21727593
TI  - Fabrication of fluorine-doped diamond-like carbon stamps for UV nanoimprint
      lithography.
AB  - Two fluorine-doped diamond-like carbon (F-DLC) stamps with sub-100 nm line
      patterns were fabricated using a direct etching method. These were applied
      successfully to ultraviolet (UV) nanoimprint lithography without requiring an
      anti-adhesion layer coating. Tests were performed to determine the optimum
      fluorine concentration for the F-DLC stamps. The ideal stamp material consisted
      of 25 at.% F-DLC with a contact angle of 85 degrees , UV transmittance of 16.4
      26.8%, and hardness of 4.5 GPa. The O(2) plasma etch rate of the DLC was
      increased considerably by the fluorine doping, making it comparable to the etch
      rate of polymethyl methacrylate (PMMA). Thus, only PMMA was used as the etch mask
      in the fabrication of the stamps.

PMID- 21727594
TI  - Argon-plasma-induced InAs/InGaAs/InP quantum dot intermixing.
AB  - We report the first study of argon (Ar)-plasma-enhanced intermixing of
      InAs/InGaAs/InP self-assembled quantum dots (QDs) in an inductively coupled
      plasma reactive ion etch system. The Ar-plasma exposure creates point defects,
      which propagate into the QD structure and enhance the intermixing between the QDs
      and their barrier layers, hence tuning the energy bandgap of the QDs. By
      optimizing the plasma exposure time and the annealing temperature, we observe (i)
      a blueshift of 160 nm and an increase in the photoluminescence (PL) intensity of
      the QD samples immediately after Ar-plasma exposure for 90 s, and (ii) a further
      increase in the blueshift of 330 nm, accompanied by 2.5-times increase in the PL
      intensity and 37 nm narrowing in the PL linewidth after subsequent rapid thermal
      annealing at 720  degrees C. The ability to generate a large blueshift without
      degrading the material quality shows that Ar-plasma exposure is an efficient post
      growth technique for tuning the energy bandgap of QD structures.

PMID- 21727595
TI  - Dependence of the cytotoxicity of multi-walled carbon nanotubes on the culture
      medium.
AB  - This study examined the influence of multi-walled carbon nanotubes (MWNTs) on the
      growth of the unicellular protozoan Tetrahymena pyriformis. Contrary to the
      findings from most other investigations, our experiment indicated that MWNTs
      stimulated growth of the cells cultured in proteose peptone yeast extract medium
      (PPY). Atomic force microscopy images and thermogravimetric analysis showed the
      spontaneous formation of peptone-MWNT conjugates in the medium by noncovalent
      binding. Uptake of large amounts of the conjugates by Tetrahymena pyriformis was
      responsible for growth stimulation, evidenced by images with fluorescently
      labelled peptone. After the PPY medium was replaced by a filtrated pond water
      medium (FPW), however, inhibition of the growth of cells exposed to MWNTs
      occurred. Measurements of the level of malondialdehyde and superoxide dismutase
      activity demonstrated further that MWNTs might be either toxic or nontoxic,
      depending on the medium used to cultivate Tetrahymena pyriformis. The biological
      effects of the interaction of MWNTs with some composites in culture media would
      be helpful for understanding the mechanisms of the toxicity of carbon nanotubes
      to living systems.

PMID- 21727596
TI  - Encapsulation of bacteria and viruses in electrospun nanofibres.
AB  - Bacteria and viruses were encapsulated in electrospun polymer nanofibres. The
      bacteria and viruses were suspended in a solution of poly(vinyl alcohol) (PVA) in
      water and subjected to an electrostatic field of the order of 1 kV cm(-1).
      Encapsulated bacteria in this work, (Escherichia coli, Staphylococcus albus) and
      bacterial viruses (T7, T4, lambda) managed to survive the electrospinning process
      while maintaining their viability at fairly high levels. Subsequently the
      bacteria and viruses remain viable during three months at -20 and -55  degrees C
      without a further decrease in number. The present results demonstrate the
      potential of the electrospinning process for the encapsulation and immobilization
      of living biological material.

PMID- 21727597
TI  - Growth mechanisms of SnO(2)/Sn nanocables.
AB  - SnO(2)/Sn nanocables have been grown on single-crystal Si substrates by metal
      catalyst assisted thermal evaporation of SnO powders. The morphologies and
      structures of the prepared nanocables were determined on the basis of field
      emission scanning electron microscopy (FESEM), high-resolution transmission
      electron microscopy (HRTEM), x-ray diffraction (XRD), Raman and photoluminescence
      (PL) spectra analyses. The microstructures and compositions of the top and bottom
      regions of the SnO(2)/Sn nanocables were identified by HRTEM in detail, which
      revealed some basic physical and chemical processes involved in the formation of
      the nanocables. A growth model was proposed to address the formation of SnO(2)/Sn
      nanocables on the basis of the vapour-liquid-solid (VLS) process.

PMID- 21727598
TI  - Synthesis of highly faceted multiply twinned gold nanocrystals stabilized by
      polyoxometalates.
AB  - A novel and facile chemical synthesis of highly faceted multiply twinned gold
      nanocrystals is reported. The gold nanocrystals are hexagonal in transmission
      electron microscopy and icosahedral in scanning electron microscopy.
      Phosphotungstic acid (PTA), which was previously reduced, serves as a reductant
      and stabilizer for the synthesis of gold nanocrystals. The PTA-gold
      nanocomposites are quite stable in aqueous solutions, and electrochemically
      active towards the hydrogen evolution reaction.

PMID- 21727599
TI  - Sol-gel assisted ZnO nanorod array template to synthesize TiO(2) nanotube arrays.
AB  - A TiO(2) nanotube array with a large surface area is fabricated on a glass
      substrate using a ZnO nanorod array and sol-gel process, and the structural
      characteristics of the TiO(2) nanotube array are investigated. The well-aligned
      ZnO nanorod array, which is deposited on ZnO seed layer coated glass substrates
      by the wet-chemical route, is used as a template to synthesize TiO(2)/ZnO
      composite nanostructures through the sol-gel process. Then, by selectively
      removing the ZnO template, a TiO(2) nanotube with contours of the ZnO nanorods is
      fabricated on the ZnO seed layer coated glass. The resultant TiO(2) nanotubes are
      1.5 um long and 100-120 nm in inner diameter, with a wall thickness of ~10 nm. In
      addition, by adjusting the experimental parameters, such as the dip-coating cycle
      number or heating rate, porous TiO(2) thick films can also be obtained.

PMID- 21727600
TI  - Properties of short channel ballistic carbon nanotube transistors with ohmic
      contacts.
AB  - We present self-consistent, non-equilibrium Green's function calculations of the
      characteristics of short channel carbon nanotube transistors, focusing on the
      regime of ballistic transport with ohmic contacts. We first establish that the
      band line-up at the contacts is renormalized by charge transfer, leading to
      Schottky contacts for small diameter nanotubes and ohmic contacts for large
      diameter nanotubes, in agreement with recent experiments. For short channel ohmic
      contact devices, source-drain tunnelling and drain-induced barrier lowering
      significantly impact the current-voltage characteristics. Furthermore, the ON
      state conductance shows a temperature dependence, even in the absence of phonon
      scattering or Schottky barriers. This last result also agrees with recently
      reported experimental measurements.

PMID- 21727601
TI  - Transmission electron microscope imaging of single-walled carbon nanotube
      interactions and mechanics on nitride grids.
AB  - A method for analysing systems of isolated single-walled carbon nanotubes is of
      paramount importance if their structural characteristics are to be fully
      understood and utilized. Here we offer a simple technique for analysing such
      systems, with unprecedented contrast, using transmission electron microscope
      imaging of carbon nanotubes suspended over large holes in a silicon nitride grid.
      The nanotubes are grown directly on the viewing grids, using the chemical vapour
      deposition process, thus avoiding the use of chemicals or aggressive treatments.
      This method is simultaneously non-invasive, reusable, allows the analysis of
      multiple structures based on carbon nanotubes and is quickly implemented.

PMID- 21727602
TI  - Synthesis and bandgap oscillation of uncapped, ZnO clusters by electroporation of
      vesicles.
AB  - A convenient preparation is reported for subnanometre size uncapped ZnO quantum
      dots, which permits the previously inaccessible live observation of the growth of
      the clusters in the molecular size regime. The preparation method utilizes
      electric field-induced transient pore formation (electroporation) in synthetic
      unilamellar vesicles. This condition allows for facile monitoring of the time
      dependent UV spectra associated with the growth of the clusters which are found
      to initially exhibit novel, oscillating red and blue shifts of the characteristic
      absorption band, ultimately followed by a monotonic red shift-the latter
      reflecting cluster growth beyond a size of ~10 A. Through a comparison of the
      observed oscillating transition energies with the corresponding trends found
      theoretically by others, the wavelengths of the sequential spectral peaks can be
      assigned to the (ZnO)(1) monomer (5.66 eV), dimer (ZnO)(2) (5.19 eV), (ZnO)(5)
      (6.21 eV), (ZnO)(12) (5.76 eV), and (ZnO)(15) (6.01 eV). Growth beyond (ZnO)(15)
      is associated with the customary monotonic red shift of the absorption band (5.59
      and 4.95 eV). The reason for oscillation of red and blue shift of the HOMO-LUMO
      gaps was explained by the structural differences of Zn(i)O(i) (i = 1-15). Under
      the experimental conditions used, a stable system is reached after 12 days. This
      solution is estimated to contain 1.4 * 10(17) (ZnO)(15) particles, each with a
      greatest dimension of ~10 A.

PMID- 21727603
TI  - Biomimetic approach to the formation of gold nanoparticle/silica core/shell
      structures and subsequent bioconjugation.
AB  - The encapsulation of individual nanoparticles has gained great attention as a
      method for both stabilizing nanoparticles and tailoring their surface properties.
      In particular, the encapsulation of nanoparticles with silica shells is
      advantageous for bioconjugation and applications to (nano)biotechnology. Herein
      we report a method for constructing gold nanoparticle (AuNP)/silica core/shell
      hybrid structures by biomimetic silicification of silicic acids. The procedure
      consists of surface-initiated, atom transfer radical polymerization of 2
      (dimethylamino)ethyl methacrylate (DMAEMA) from AuNPs and biomimetic
      polycondensation of silicic acids by using poly(DMAEMA) as a synthetic
      counterpart for silaffins that are found in diatoms. The resulting AuNP/silica
      hybrids were characterized by Fourier transform infrared spectroscopy, energy
      dispersive x-ray spectroscopy, UV-vis spectroscopy and transmission electron
      microscopy. In addition, the immobilization of biological ligands onto the
      hybrids was investigated for potential applications to biotechnology. As a model
      ligand, biotin was attached onto the AuNP/silica hybrids through substitution
      reaction and Michael addition reaction, and the attachment was confirmed by
      fluorescence microscopy after complexation with fluorescein-conjugated
      streptavidin.

PMID- 21727604
TI  - Structural transformation of partially confined copper nanowires inside defected
      carbon nanotubes.
AB  - The encapsulated copper atoms inside a defected single-walled carbon nanotube
      escape from the tube through the defect hole as the temperature increases. This
      causes the partially confined copper nanowires (CNWs) to undergo special
      structural transformations from a solid to a distinguishable helical layered
      structure and finally to the liquid state. The defect has a vital function in
      automatically adjusting the internal pressure and copper atom density. The
      critical structural transformation temperature of the CNW is significantly
      influenced by the confinement conditions of the carbon nanotube.

PMID- 21727605
TI  - A simple solution route to controlled synthesis of ZnS submicrospheres,
      nanosheets and nanorods.
AB  - ZnS nanostructures with different morphologies of submicrospheres, nanosheets and
      nanorods were synthesized by solution precipitation of thiourea with Zn(NO(3))(2)
      in the presence of block copolymer at low temperature. The sizes and morphologies
      of ZnS can be controlled simply by changing the processing parameters. The
      results show that the ZnS submicrospheres are of 250-500 nm in diameter,
      nanosheets are 2.5 um * 5.5 um with an estimated thickness of 20-30 nm, and
      nanorods are 2-5 nm in diameter and 10-30 nm in length. Keeping the precursor
      system in an autoclave at 105  degrees C results in the formation of ZnS
      submicrospheres; ultrasonication and keeping the system at room temperature leads
      to the formation of ZnS nanosheets; and long-time continuous ultrasonication and
      keeping the system in an autoclave at 105  degrees C induces the formation of
      uniform ZnS nanorods. We argue that the reaction temperature and P123 may play
      crucial roles in the formation of three ZnS structures in this work. The
      morphologically controllable synthesis strategies may be extended to the shape
      controlled production of nanostructures of other inorganic materials.

PMID- 21727606
TI  - Synthesis of high quality zinc-blende CdSe nanocrystals and their application in
      hybrid solar cells.
AB  - Oleic acid (OA) modified zinc-blende cadmium selenium nanocrystals (NCs) with
      different diameters, 3-5 nm, have been prepared. We find that the morphology and
      fluorescent properties of the samples are related to the preparation conditions
      such as the chain-length and concentration of the cadmium precursor as well as
      the concentration of OA. The hybrid solar cells based on the obtained spherical
      CdSe NCs as an acceptor and Poly(2-methoxy-5-(2'-ethylhexoxy)-p
      phenylenevinylene) (MEH-PPV) as a donor show an energy conversion efficiency
      (ECE) as high as 0.85%, three times higher than that reported before for
      spherical CdSe NCs/conjugated polymer hybrid solar cells. When poly(3
      hexylthiophene) (P3HT) is used as the donor phase instead of MEH-PPV, the energy
      conversion efficiency increases up to 1.08%. The solar cell based on CdSe
      NCs/conjugated polymer has the potential to open up new production technologies
      for hybrid solar cells based on semiconductor NCs.

PMID- 21727607
TI  - Effect of the growth rate on the morphology and structural properties of hut
      shaped Ge islands in Si(001).
AB  - The effect of Ge deposition rate on the morphology and structural properties of
      self-assembled Ge/Si(001) islands was studied. Ge/Si(001) layers were grown by
      solid-source molecular-beam epitaxy at 500  degrees C. We adjusted the Ge
      coverage, 6 monolayers (ML), and varied the Ge growth rate by a factor of 100, R
      = 0.02-2 ML s(-1), to produce films consisting of hut-shaped Ge islands. The
      samples were characterized by scanning tunnelling microscopy, Raman spectroscopy,
      and Rutherford backscattering measurements. The mean lateral size of Ge
      nanoclusters decreases from 14.1 nm at R = 0.02 ML s(-1) to 9.8 nm at R = 2 ML s(
      1). The normalized width of the size distribution shows non-monotonic behaviour
      as a function of R and has a minimum value of 19% at R = 2 ML s(-1). Ge
      nanoclusters fabricated at the highest deposition rate demonstrate the best
      structural quality and the highest Ge content (~0.9).

PMID- 21727608
TI  - The effect of added oversized elements on the microstructure of binary alloy
      nanoparticles.
AB  - Molecular dynamics simulations are used to investigate the microstructures of Cu
      Ni nanoparticles with different concentrations of oversized atoms added to them.
      A many body second moment tight binding approximation potential is adopted to
      model the interatomic interactions. The Honeycutt-Anderson (HA) pair analysis
      technique is adopted to analyse in detail the transformation between local
      structures at different temperatures. From the simulation results, at
      temperatures higher than the melting point, the nanoparticles are in a liquid
      state and an icosahedral local structure is most frequently found inside the
      nanoparticles. At temperatures beneath the melting point, the fraction of FCC
      local structure increases with decreasing concentrations of the larger size
      atoms, whereas a larger fraction of amorphous structure still remains in the
      solid state for higher concentrations of oversized atoms. This is because the
      effects of distortion and misfit are more significant for a nanoparticle having a
      higher concentration of oversized atoms.

PMID- 21727609
TI  - Seed-mediated synthesis of branched gold nanoparticles with the assistance of
      citrate and their surface-enhanced Raman scattering properties.
AB  - We report an easy synthesis of highly branched gold particles through a seed
      mediated growth approach in the presence of citrate. The addition of citrate in
      the growth solution is found to be crucial for the formation of these branched
      gold particles. Their size can be varied from 47 to 185 nm. The length of the
      thumb-like branch is estimated to be between about 5 and 20 nm, and changes
      slightly as the particle size increases. Owing to these obtuse and short
      branches, their surface plasmon resonance displays a marked red-shift with
      respect to the normal spherical particles. These branched gold particles exhibit
      stronger SERS activity than the non-branched ones, which is most likely related
      to these unique branching features.

PMID- 21727610
TI  - Evidence for intergranular tunnelling in polyaniline passivated alpha-Fe
      nanoparticles.
AB  - Nanoparticles are of immense importance both from the fundamental and application
      points of view. They exhibit quantum size effects which are manifested in their
      improved magnetic and electric properties. Mechanical attrition by high energy
      ball milling (HEBM) is a top down process for producing fine particles. However,
      fineness is associated with high surface area and hence is prone to oxidation
      which has a detrimental effect on the useful properties of these materials.
      Passivation of nanoparticles is known to inhibit surface oxidation. At the same
      time, coating polymer film on inorganic materials modifies the surface properties
      drastically. In this work a modified set-up consisting of an RF plasma
      polymerization technique is employed to coat a thin layer of a polymer film on Fe
      nanoparticles produced by HEBM. Ball-milled particles having different particle
      size ranges are coated with polyaniline. Their electrical properties are
      investigated by measuring the dc conductivity in the temperature range 10-300 K.
      The low temperature dc conductivity (I-V) exhibited nonlinearity. This
      nonlinearity observed is explained on the basis of the critical path model. There
      is clear-cut evidence for the occurrence of intergranular tunnelling. The results
      are presented here in this paper.

PMID- 21727611
TI  - One-step formation of core-shell sulfide-oxide nanorod arrays from a single
      precursor.
AB  - Densely packed and well-aligned coaxial (core-shell) CdS-CdO and ZnS-ZnO nanorod
      arrays were prepared with a one-step, non-catalytic, template-free metalorganic
      chemical vapour deposition (MOCVD) process by using single-source molecular
      precursors Cd(O-EtXan)(2) and Zn(O-EtXan)(2), respectively (O-EtXan =
      S(2)COCH(2)CH(3)). Data from pyrolysis gas chromatography/mass spectrometry of
      the precursors revealed the sequence of formation, namely sulfide core first and
      oxide shell later, with the first formed sulfide nanorods serving as the template
      for subsequent in situ oxide shell coating. The coaxial CdS-CdO and ZnS-ZnO
      nanorod arrays were formed at collection temperatures of 180 and 200  degrees C,
      respectively. At a slightly higher collection temperature of 250  degrees C,
      coaxial ZnS-ZnO nanowires were also obtained. The coaxial nanostructure was
      characterized and confirmed with high-resolution transmission electron
      microscopy. In a photoluminescence study, near band edge emissions at around 530
      nm, a composite emission of the two near band edge emissions of 524 nm of CdS and
      551 nm of CdO, were observed for the coaxial CdS-CdO nanorod sample, while defect
      induced emissions at around 470 nm were observed for both coaxial ZnS-ZnO nanorod
      and nanowire samples. A more stable oxide shell not only protects the sulfide
      core but also provides possible surface passivation beneficial to enhanced
      photoluminescence. The present work demonstrates the feasibility of growth of
      coaxial one-dimensional nanostructures from single-source precursors that contain
      all the necessary constituent elements in one compound.

PMID- 21727612
TI  - Ba3Y2B6O15, a novel cubic borate.
AB  - Single crystals of tribarium diyttrium hexaborate, which crystallized in the
      cubic system, have been obtained by spontaneous crystallization from a high
      temperature melt using Li(2)O-BaO-B(2)O(3) as flux. Its structure is composed of
      isolated [B(2)O(5)](4-) groups, irregular BaO(9) polyhedra and regular YO(6)
      polyhedra which occupy alternate sites running along the [111] direction.
      Irregular BaO(9) polyhedra and regular YO(6) polyhedra construct a three
      dimensional framework, which is reinforced by [B(2)O(5)](4-) groups.

PMID- 21727613
TI  - A new rhombohedral modification of EuNi5In.
AB  - A rhombohedral modification of europium pentanickel indide, r-EuNi(5)In,
      crystallizes in the R 3m space group and adopts the UCu(5)In structure type. The
      structure is closely related to the hexagonal, h-EuNi(5)In, form (CeNi(5)Sn
      type). Both EuNi(5)In modifications are composed of CaCu(5) (EuNi(5))-, MgCu(2)
      (InNi(2))- and NiAs (EuNi)-type slabs in a 1:2:1 ratio. The atoms in the
      structure have high coordination numbers, viz. 20 and 18 for europium, 14 for
      indium, and 12 and 10 for nickel. The structure features a two-dimensional
      network of (2)(infinity)[Ni(8)] tetrahedral clusters arranged in the ab plane.

PMID- 21727614
TI  - Bis(tert-butyl isocyanide-kappaC)[4-fluoro-N-({2-[N-(4
      fluorophenyl)carboximidoyl]cyclopenta-2,4-dien-1-ylidene}methyl)anilinido
      kappa2N,N']copper(I).
AB  - The solid-state structure of the title compound,
      [Cu(C(19)H(13)F(2)N(2))(C(5)H(9)N)(2)], shows that the Cu(I) centre adopts a
      distorted tetrahedral coordination geometry, being coordinated by two N atoms of
      the 6-aminofulvene-2-aldimine (AFA) chelating ligand and by the bridgehead C
      atoms of the two isocyanide ligands. The cyclopentadienyl and imine components of
      the AFA ligand are approximately coplanar, with an angle between the planes of
      5.00 (3) degrees . The Cu atom lies 0.6460 (3) A above the imine plane defined by
      the N and C atoms of the seven-membered metallocycle. There is also an uncommon C
      H...Cu anagostic interaction, with an intramolecular Cu...H distance of 2.67 A,
      which is less than the sum of the van der Waals radii.

PMID- 21727615
TI  - A two-dimensional undulating Ag(I) coordination polymer constructed of Ag-C and
      Ag-O bonds: poly[[[MU3-(5,6-eta):kappaO(2):kappaO(2)-(+/-)-(1S,2S,3R,4R)-3
      carboxy-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylato]silver(I)] monohydrate].
AB  - The title coordination polymer, {[Ag(C(8)H(7)O(5))].H(2)O}(n), is built from
      Ag(+) cations and singly protonated dehydronorcantharidin (SP-DNC) anions, with a
      distorted trigonal-planar geometry at the metal centre. The coordination number
      of Ag(I) is three (with one Ag-pi bond and two Ag-O bonds, one from each of three
      different SP-DNC ligands), if only formal Ag-ligand bonds are considered, but can
      be regarded as five if longer weak Ag...O interactions are also included. The two
      dimensional corrugated-sheet coordination polymer forms a non-interpenetrating
      framework with (4.8(2)) topology. Disordered water molecules are sandwiched
      between the sheets.

PMID- 21727616
TI  - [Cl5Ta(MU-O)TaCl3{(i)PrS(CH2)2S(i)Pr}] and [(TaCl4)2(MU-O)(MU-Me2Se2)]: two
      chalcogenoether complexes of Ta2OCl8 with very different geometries.
AB  - The title compounds, [1,2-bis(isopropylsulfanyl)ethane-2kappa(2)S,S']octachlorido
      1kappa(5)Cl,2kappa(3)Cl-MU-oxido-ditantalum(V), [Ta(2)Cl(8)O(C(8)H(18)S(2))],
      (I), and MU-dimethyldiselane-kappa(2)Se:Se'-MU-oxido
      bis[tetrachloridotantalum(V)], [Ta(2)Cl(8)O(C(2)H(6)Se(2))], (II), contain six
      coordinate Ta(V) centres linked by a nonlinear oxide bridge. Compound (I)
      contains one Ta(V) centre bonded to a chelating dithioether and three terminal
      chloride ligands, with the second Ta(V) centre bonded to five terminal chloride
      ligands. In (II), two tetrachloridotantalum(V) residues are bridged by the
      diselenide, giving a puckered five-membered Ta/O/Ta/Se/Se ring. The Ta-O
      distances in the bridges are short in both compounds, indicating that significant
      multiple-bond character is retained despite the deviation from linearity, and the
      bond lengths reveal a clear trans influence order of O > Cl > S > Se on the hard
      Ta(V) centre. The structures are compared with the [Ta(2)Cl(10)O](2-) anion,
      which contains a linear oxide bridge.

PMID- 21727617
TI  - Poly[aqua[MU2-1,4-bis(imidazol-1-ylmethyl)benzene-kappa2N3:N3'](MU2-5
      hydroxybenzene-1,3-dicarboxylato-kappa4O1,O1':O3,O3')cadmium(II)], a twofold
      interpenetrated CdSO4-like metal-organic polymer.
AB  - In the title cadmium(II) complex, [Cd(C(8)H(4)O(5))(C(14)H(14)N(4))(H(2)O)](n),
      the 5-hydroxybenzene-1,3-dicarboxylate (5-OH-1,3-bdc) and 1,4-bis(imidazol-1
      ylmethyl)benzene (1,4,-bix) ligands bridge water-coordinated Cd(II) atoms to
      generate a three-dimensional network. Two carboxylate groups from different
      ligands function as O,O'-chelates, while two imidazole N atoms from different
      ligands coordinate in a monodentate fashion, and one water molecule completes the
      seven-coordinate pentagonal bipyramid around the Cd(II) atom, in which the N
      atoms occupy the axial sites and the O atoms occupy the equatorial sites. The
      overall architecture is a twofold interpenetrated CdSO(4)-type framework. The two
      crystallographically equivalent frameworks are linked by O-H...O hydrogen bonds
      between the water, hydroxy and carboxylate groups.

PMID- 21727618
TI  - A chiral interdigitated supramolecular network assembled from single-stranded
      helical tubes.
AB  - The amino-functionalized helical chiral one-dimensional coordination polymer
      catena-poly[[bis(pyridine-kappaN)zinc(II)]-MU-2-aminobenzene-1,4-dicarboxylato
      kappa(4)O(1),O(1'):O(4),O(4')], [Zn(C(8)H(5)NO(4))(C(5)H(5)N)(2)](n), has an
      extended structure that is assembled from 2-aminobenzene-1,4-dicarboxylate anions
      and Zn(2+) cations and which presents a left-handed 4(3) helix with a pitch of
      25.6975 (9) A. All the pyridine rings and all the amino groups point away from
      the helix to generate a hollow tube with a cross-section of approximately 8 * 8 A
      running parallel to the crystallographic c direction. Each single-stranded helix
      is interdigitated with four neighbouring helices via N-H...O hydrogen bonds,
      which gives rise to a dense homochiral three-dimensional supramolecular network.

PMID- 21727619
TI  - catena-Poly[[[(di-2-pyridylamine-kappa2N2,N2')copper(II)]-MU-benzene-1,3
      dicarboxylato-kappa3O1,O1':O3] monohydrate], a zigzag coordination polymer with
      strong pi-pi interactions.
AB  - The novel title coordination polymer,
      {[Cu(C(8)H(4)O(4))(C(10)H(9)N(3))].H(2)O}(n), synthesized by the slow-diffusion
      method, takes the form of one-dimensional zigzag chains built up of Cu(II)
      cations linked by benzene-1,3-dicarboxylate (ipht) anions. An exceptional
      characteristic of this structure is that it belongs to a small group of metal
      organic polymers where ipht is coordinated as a bridging tridentate ligand with
      monodentate and chelate coordination of individual carboxylate groups. The Cu(II)
      cation has a highly distorted square-pyramidal geometry formed by three O atoms
      from two ipht anions and two N atoms from a di-2-pyridylamine (dipya) ligand. The
      zigzag chains, which run along the b axis, further construct a three-dimensional
      metal-organic framework via strong face-to-face pi-pi interactions and hydrogen
      bonds. A solvent water molecule is linked to the different carboxylate groups via
      hydrogen bonds. Thermogravimetric and differential scanning calorimetric analyses
      confirm the strong hydrogen bonding.

PMID- 21727620
TI  - Di-MU-chlorido-bis[dichloridobis(methylamido-kappaN)bis(methylamine
      kappaN)titanium(IV)].
AB  - The title compound, [Ti(2)Cl(6)(C(2)H(6)N)(2)(C(2)H(7)N)(2)], is a binuclear
      octahedral complex lying about an inversion centre. There are four different
      chloride environments, two terminal [Ti-Cl = 2.2847 (5) and 2.3371 (5) A] and two
      bridging [Ti-Cl = 2.4414 (5) and 2.6759 (5) A], with the Ti-Cl distances being
      strongly influenced by both the ligand trans to the chloride and whether or not
      the chloride anion is bridging between the two Ti(IV) centres. The compound forms
      a two-dimensional network in the solid state, with weak intermolecular C-H...Cl
      interactions giving rise to a planar network in the (10 2) plane.

PMID- 21727621
TI  - Mercury(II) thiolate complexes of two flexible benzimidazole-based ligands.
AB  - The structure of catena-poly[[{bis[4-(trimethylammonio)benzenethiolate
      kappaS]mercury(II)}-MU-1,1'-(ethane-1,2-diyl)bis(1H-benzimidazole)
      kappa(2)N(3):N(3')] bis(hexafluoridophosphate) 0.25-hydrate],
      {[Hg(C(16)H(14)N(4))(C(9)H(13)NS)(2)](PF(6))(2).0.25H(2)O}(n), contains a one
      dimensional zigzag chain. The Hg(II) cation is coordinated by two S atoms of two
      4-(trimethylammonio)benzenethiolate (Tab) ligands and by two N atoms from two
      different 1,1'-(ethane-1,2-diyl)bis(1H-benzimidazole) ligands, forming a
      distorted seesaw-shaped coordination geometry. The F atoms of the
      hexafluoridophosphate anion interact with the H atoms of the Tab ligand,
      generating a two-dimensional network. Furthermore, this layer is connected to
      neighbouring layers via H...pi interactions, thereby forming a three-dimensional
      hydrogen-bonded structure. In catena-poly[[{[4-(trimethylammonio)benzenethiolate
      kappaS]mercury(II)}bis[MU-4-(trimethylammonio)benzenethiolate-kappa(2)S:S]{[4
      (trimethylammonio)benzenethiolate-kappaS]mercury(II)}-MU-1,1'-(hexane-1,6
      diyl)bis(1H-benzimidazole)-kappa(2)N(3):N(3')] tetrakis(hexafluoridophosphate)],
      {[Hg(2)(C(20)H(22)N(4))(C(9)H(13)NS)(4)](PF(6))(4)}(n), each Hg(II) cation is
      coordinated by two S atoms of two Tab ligands and one N atom of the 1,1'-(hexane
      1,6-diyl)bis(1H-benzimidazole) (hbbm) ligand, forming a distorted T-shaped
      coordination geometry, while longer secondary Hg...S bonds join two such units
      across a centre of inversion to give the tetravalent cation. Adjacent
      {[Hg(Tab)(2)](2)(MU-hbbm)}(4+) cations are linked through the centrosymmetric
      hbbm ligands to afford a one-dimensional chain extending along the b axis.
      Several F atoms interact with the H atoms of the Tab and hbbm ligands, while the
      S atom interacts with an aromatic H atom of a different Tab ligand, to afford a
      complex intra- and intermolecular hydrogen-bonding arrangement in a three
      dimensional structure.

PMID- 21727622
TI  - Bis(acetonitrile-kappaN)bis[hydridotris(3,5-dimethylpyrazol-1-yl
      kappaN2)borato]di-MU3-sulfido-tetra-MU2-sulfido-di-MU2-thiocyanato
      kappa2N:S;kappa2S:N-tetracopper(I)ditungsten(VI).
AB  - Reactions of (Et(4)N)[Tp*WS(3)] [Tp* is hydridotris(3,5-dimethylpyrazol-1
      yl)borate] with CuSCN in MeCN in the presence of melamine afforded the title
      neutral dimeric cluster [Cu(4)W(2)(C(15)H(22)BN(6))(2)(NCS)(2)S(6)(C(2)H(3)N)(2)]
      or [Tp*W(MU(2)-S)(2)(MU(3)-S)Cu(MU(2)-SCN)(CuMeCN)](2), which has two butterfly
      shaped [Tp*WS(3)Cu(2)] cores bridged across a centre of inversion by two (CuSCN)(
      ) anions. The S atoms of the bridging thiocyanate ligands interact with the H
      atoms of the methyl groups of the Tp* units of a neighbouring dimer to form a C
      H...S hydrogen-bonded chain. The N atoms of the thiocyanate anions interact with
      the H atoms of the methyl groups of the Tp* units of neighbouring chains,
      affording a two-dimensional hydrogen-bonded network.

PMID- 21727623
TI  - The Knoevenagel product of indolin-2-one and ferrocene-1,1'-dicarbaldehyde.
AB  - Indolin-2-one (oxindole), (I), undergoes a Knoevenagel condensation with
      ferrocene-1,1'-dicarbaldehyde, (II), to afford the title complex 3,3'-[(E,E)
      ferrocene-1,1'-diyldimethylidyne]diindolin-2-one dichloromethane disolvate,
      [Fe(C(28)H(20)N(2)O(2))].2CH(2)Cl(2), (IV). The structure of (IV) contains two
      ferrocene complex molecules in the asymmetric unit and displays, as expected,
      intermolecular hydrogen bonding (N-H...O=C) between the indolin-2-one units.
      Intermolecular pi-pi stacking interactions are also observed.

PMID- 21727624
TI  - A new polymeric alkyl/alkoxide magnesium-sodium inverse crown complex.
AB  - Poly[bis(MU(3)-trimethylsilylmethanolato)tetrakis(MU(2)
      trimethylsilylmethyl)dimagnesiumdisodium],
      [Na(2)Mg(2)(C(4)H(11)OSi)(2)(C(4)H(11)Si)(4)](n), was obtained from the
      controlled exposure to oxygen of the unsolvated sodium magnesate
      [NaMg(CH(2)SiMe)(3)](n). Exhibiting a centrosymmetric (Z' = 1/2) dimeric core of
      a heterobimetallic eight-membered cationic ring, hosting two alkoxide ligands at
      its core, the title compound forms a two-dimensional coordination polymer in the
      crystallographic bc plane through Na...Me contacts. These contacts from Na to
      formally uncharged groups are only 0.06 longer than those between Na and the
      formally charged CH(2)R anions. The coordination polymers stack along the a
      direction to give a layer structure with alternating hydrophobic and hydrophilic
      regions.

PMID- 21727625
TI  - A MU4-oxide-containing a dimeric variant of a sodium dialkyl(amido)zincate
      reagent.
AB  - Post-metallation derivatives of the sodium dialkyl(amido)zincate reagent
      (TMEDA)Na(MU-TMP)Zn((t)Bu)(2) (TMEDA is N,N,N',N'-tetramethylethylenediamine and
      TMP is 2,2,6,6-tetramethylpiperidide) have been of structural interest due to the
      insight they give into aromatic metallation mechanisms. Here, the aromatic
      substrate is formally replaced with [ZnO](2) to give tetra-tert-butyldi-MU(4)
      oxido-bis(tetramethylethylenediamine-kappa(2)N,N')bis(MU(2)-2,2,6,6
      tetramethylpiperidin-1-ido-kappa(2)N:N)disodiumtetrazinc hexane 0.59-solvate,
      [Na(2)Zn(4)(C(4)H(9))(4)(C(9)H(18)N)(2)O(2)(C(6)H(16)N(2))(2)].0.59C(6)H(14). The
      crystallographically centrosymmetric complex retains many of the structural
      features of its parent monomer but has an unusual dimeric structure, with a
      central planar Zn-O-Zn-O ring joined to two orthogonal near-planar Zn-O-Na-N
      rings through the distorted tetrahedral geometries of the oxide ions.

PMID- 21727626
TI  - Structural trends in a series of isostructural lanthanide-copper metallacrown
      sulfates (Ln(III) = Pr, Nd, Sm, Eu, Gd, Dy and Ho): hexaaquapentakis[MU3
      glycinehydroxamato(2-)]sulfatopentacopper(II)lanthanide(III)
      heptaaquapentakis[MU3-glycinehydroxamato(2
      )]sulfatopentacopper(II)lanthanide(III) sulfate hexahydrate.
AB  - The seven isostructural complexes,
      [Cu(5)Ln(C(2)H(4)N(2)O(2))(5)(SO(4))(H(2)O)(6.5)](2)(SO(4)).6H(2)O, where Ln(III)
      = Pr, Nd, Sm, Eu, Gd, Dy and Ho, are representatives of the 15-metallacrown-5
      family. Each dianion of glycinehydroxamic acid (GlyHA) links two Cu(II) cations
      forming a cyclic [CuGlyHA](5) frame. The Ln(III) cations are located at the
      centre of the [CuGlyHA](5) rings and are bound by the five hydroxamate O atoms in
      the equatorial plane. Five water molecules are coordinated to Cu(II) cations, and
      one further water molecule, located close to an inversion centre between two
      adjacent [Cu(5)Ln(GlyHA)(5)](2+) cations, is disordered around this inversion
      centre and coordinated to a Cu(II) cation of either the first or second
      metallacrown ether. Another water molecule and one of the two
      crystallographically independent sulfate anions are coordinated, the latter in a
      bidentate fashion, to the Ln(III) cation in the axial positions. The second
      sulfate anion is not coordinated to the cation, but is located in an interstitial
      position on a crystallographic inversion centre, thus leading to disorder of the
      O atoms around the centre of inversion. The Ln-O bond distances follow the trend
      of the lanthanide contraction. The apical Ln-O bond distances are very close to
      the sums of the ionic radii. However, the Ln-O distances within the metallacrown
      units are slightly compressed and the Ln(III) cations protrude significantly from
      the plane of the otherwise flat metallacrown ligand, thus indicating that the
      cavity is somewhat too small to accommodate the Ln(III) ions comfortably. This
      effect decreases with the size of the lanthanide cation from complex (I) (Ln(III)
      = Pr; 0.459) to complex (VII) (Ln(III) = Ho; 0.422), which indicates that the
      smaller lanthanide cations fit the cavity of the pentacopper metallacrown ring
      better than the larger ones. The diminished contraction of Ln-O distances within
      the metallacrown planes leads to an aniostropic contraction of the unit-cell
      parameters, with a, c and V following the trend of the lanthanide contraction.
      The b axes, which are mostly aligned with the rigid planes of the metallacrown
      units, show only a little variation between the seven compounds.

PMID- 21727627
TI  - New coordination modes in potassium edta salts: K2[H2edta]2H2O, K3[Hedta]2H2O and
      K4[edta].3.92H2O.
AB  - Three potassium edta (edta is ethylenediaminetetraacetic acid, H(4)Y) salts which
      have different degrees of ionization of the edta anion, namely dipotassium 2-({2
      [bis(carboxylatomethyl)azaniumyl]ethyl}(carboxylatomethyl)azaniumyl)acetate
      dihydrate, 2K(+).C(10)H(14)N(2)O(8)(2-).2H(2)O, (I), tripotassium 2,2'-({2
      [bis(carboxylatomethyl)amino]ethyl}ammonio)diacetate dihydrate,
      3K(+).C(10)H(13)N(2)O(8)(3-).2H(2)O, (II), and tetrapotassium 2,2',2'',2'''
      (ethane-1,2-diyldinitrilo)tetraacetate 3.92-hydrate, 4K(+).C(10)H(12)N(2)O(8)(4
      ).3.92H(2)O, (III), were obtained in crystalline form from water solutions after
      mixing edta with potassium hydroxide in different molar ratios. In (II), a new
      mode of coordination of the edta anion to the metal is observed. The HY(3-) anion
      contains one deprotonated N atom coordinated to K(+) and the second N atom is
      involved in intramolecular bifurcated N-H...O and N-H...N hydrogen bonds. The
      overall conformation of the HY(3-) anions is very similar to that of the Y(4-)
      anions in (III), although a slightly different spatial arrangement of the 
      CH(2)COO(-) groups in relation to (III) is observed, whereas the H(2)Y(2-) anions
      in (I) adopt a distinctly different geometry. The preferred synclinal
      conformation of the -NCH(2)CH(2)N- moiety was found for all edta anions. In all
      three crystals, the anions and water molecules are arranged in three-dimensional
      networks linked via O-H...O and C-H...O [and N-H...O in (I) and (II)] hydrogen
      bonds. K...O interactions also contribute to the three-dimensional polymeric
      architecture of the salts.

PMID- 21727628
TI  - Bis(methyltri-o-tolylphosphonium) octaiodide.
AB  - In the crystal structure of the title compound, 2C(22)H(24)P(+).I(8)(2-), the
      I(8)(2-) anion is located on a crystallographic inversion centre and consists of
      two tri-iodide anions linked by di-iodine at angles of 89.92 4) degrees  to form
      a planar 'Z'-shaped dianion. The octaiodides are linked via long-range
      interactions [3.877 11) ] into infinite polyiodide ribbons. This is the first
      example of a structure containing an [(o-tolyl)(3)PMe](+) cation, and the C(Me)-P
      C-C(Me) torsion angles of -54.0 11), -51.3 11) and -48.2 11) degrees  indicate
      that the configuration is exo(3).

PMID- 21727629
TI  - 1-(9H-Carbazol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol
      hemihydrate: a carvedilol solvatomorph.
AB  - In the title racemic hemihydrated solvatomorph of carvedilol (carv),
      C(24)H(26)N(2)O(4).0.5H(2)O, the asymmetric unit contains two independent organic
      moieties and one water molecule. Within this 2(carv).H(2)O unit, the molecular
      components are strongly linked by hydrogen bonds and the unit acts as the basic
      building block for the crystal structure. Interactions parallel to (10 1)
      generate hydrogen-bonded layers which are further linked by much weaker C-H...N/O
      interactions. The conformations of the organic molecules, as well as the hydrogen
      bonding interactions connecting them, are compared with other related structures
      in the literature.

PMID- 21727630
TI  - The discrete role of chlorine substitutions in the conformation and
      supramolecular architecture of arylsulfonamides.
AB  - Two arylsulfonamide derivatives, N-(4-acetylphenyl)benzenesulfonamide,
      C(14)H(13)NO(3)S, and N-(4-acetylphenyl)-2,5-dichlorobenzenesulfonamide,
      C(14)H(11)Cl(2)NO(3)S, differing by the absence or presence of two chloro
      substituents on one of the phenyl rings, were synthesized and characterized in
      order to establish structural relationships and the role of chloro substitution
      on the molecular conformation and crystal assembly. Both arylsulfonamides form
      inversion-related dimers through C-H...pi and pi-pi interactions. These dimers
      pack in a similar way in the two structures. The substitution of two H atoms at
      the 2- and 5-positions of one phenyl ring by Cl atoms did not substantially alter
      the molecular conformation or the intermolecular architecture displayed by the
      unsubstituted sulfonamide. The structural information controlling the assembly of
      such compounds in their crystal phases is in the (phenyl)benzenesulfonamide
      molecular framework.

PMID- 21727631
TI  - A structural and theoretical study of the intermolecular interactions in 8
      hydroxyquinolinium-7-carboxylate monohydrate.
AB  - In the title compound, C(10)H(7)NO(3).H(2)O, the zwitterionic organic molecules
      and the water molecules are connected by N-H...O and O-H...O hydrogen bonds to
      form ribbons, and pi-pi stacking interactions expand these ribbons into a three
      dimensional net. The energies of these hydrogen bonds adopt values typical for
      mildly weak interactions (3.33-7.75 kcal mol(-1); 1 kcal mol(-1) = 4.184 kJ mol(
      1)). The total pi-pi stacking interactions between aromatic molecules can be
      classified as mildly strong (energies of 15.3 and 33.9 kcal mol(-1)), and they
      are made up of multiple constituent pi-pi interactions between six-membered
      rings. The short intermolecular C-H...O contact between two zwitterionic
      molecules is nonbonding in character.

PMID- 21727632
TI  - Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic
      activity. III. Mono- and diesters of 3-(pyrazin-2-ylcarbonyl)dithiocarbazic acid.
AB  - Methyl 2-(pyrazin-2-ylcarbonyl)hydrazinecarbodithioate, C(7)H(8)N(4)OS(2), (E1),
      N'-[bis(methylsulfanyl)methylidene]pyrazine-2-carbohydrazide, C(8)H(10)N(4)OS(2),
      (F1), N'-[bis(methylsulfanyl)methylidene]-6-methoxypyrazine-2-carbohydrazide,
      C(9)H(12)N(4)O(2)S(2), (F2), and methyl 1-methyl-2-(pyrazin-2
      ylcarbonyl)hydrazinecarbodithioate, C(8)H(10)N(4)OS(2), (G1), can be considered
      as derivatives of classical (thio)amide-type tuberculostatics, and all are
      moderately active against Mycobacterium tuberculosis. This study was undertaken
      in a search for relationships between activity and specific intramolecular
      interactions, especially conjugations and hydrogen-bond contacts, and the
      molecular structures were compared with respective amine analogues, also active
      against the pathogen. Despite the differences between the amine and carbonyl
      groups with opposite functions in the hydrogen bond, the two types of structure
      show a surprisingly similar planar geometry, mostly due to the conjugations aided
      by the bifurcated intramolecular hydrogen-bond contact between the N-H group of
      the central hydrazide group as donor and a pyrazine N atom and an S atom of the
      dithio function as acceptors. Planarity was suggested to be crucial for the
      tuberculostatic activity of these compounds. The N-methylated derivative (G1)
      showed a significant twist at the N-N bond [torsion angle = -121.9 (3) degrees ]
      due to the methyl substitution, which precludes an intramolecular N-H...S contact
      and the planarity of the whole molecule. Nonetheless, the compound shows moderate
      tuberculostatic activity.

PMID- 21727633
TI  - beta-Carboline (norharman).
AB  - The structure of beta-carboline, also called norharman (systematic name: 9H
      pyrido[3,4-b]indole), C(11)H(8)N(2), has been determined at 110 K. Norharman is
      prevalent in the environment and the human body and is of wide biological
      interest. The structure exhibits intermolecular N-H...N hydrogen bonding, which
      results in a one-dimensional herringbone motif. The three rings of the norharman
      molecule collectively result in a C-shaped curvature of 3.19 (13) degrees 
      parallel to the long axis. The diffraction data show shorter pyridyl C-C bonds
      than those reported at the STO-3G level of theory.

PMID- 21727634
TI  - Supramolecular structures constructed by 3-(2-amino-6-chloropyrimidin-4-yl)-1,1
      dimethylprop-2-yn-1-ol monohydrate and 3-[2-amino-6-(3-hydroxy-3,3-dimethylprop-1
      yn-1-yl)pyrimidin-4-yl]-1,1-dimethylprop-2-yn-1-ol.
AB  - The molecule of 3-(2-amino-6-chloropyrimidin-4-yl)-1,1-dimethylprop-2-yn-1-ol
      monohydrate, C(9)H(10)ClN(3)O.H(2)O, (I), shows a very polarized molecular
      electronic structure, while the polarization is slight for 3-[2-amino-6-(3
      hydroxy-3,3-dimethylprop-1-yn-1-yl)pyrimidin-4-yl]-1,1-dimethylprop-2-yn-1-ol,
      C(14)H(17)N(3)O(2), (II). In the supramolecular structure of (I), a combination
      of hard N-H...N hydrogen bonds and soft C-H...N hydrogen bonds creates a
      molecular column. Aromatic pi-pi stackings between the pyrimidine rings stabilize
      the column with perpendicular and centroid-centroid distances of 3.283 (3) and
      3.588 (1) A, respectively. Short Cl...Cl contacts further link neighbouring
      molecular columns, creating a hydrophilic tube in which water molecules are fixed
      by various hydrogen bonds. In the packing of (II), a one-dimensional molecular
      chain is formed through several contacts involving hard N-H...O(N) and O-H...O(N)
      and soft C-H...O hydrogen bonds. Interchain O-H...O hydrogen bonds link the
      chains giving a two-dimensional stepped network. It is anticipated that study of
      the influence of hydrogen bonding on the patterns of base pairing and molecular
      packing in aminopyrimidine structures will shed significant light on nucleic acid
      structures as well as their functions.

PMID- 21727635
TI  - Polysulfonylamines. CXCI. The 'almost' polymorphs rac-trans-2-aminocyclohexan-1
      aminium di(methanesulfonyl)azanide and its 0.11-hydrate.
AB  - The title compound, C(6)H(15)N(2)(+).C(2)H(6)NO(4)S(2)(-), crystallizes as a 0.11
      hydrate, (I), in the space group C2; the asymmetric unit consists of two cations
      (one of each enantiomer), one anion on a general position, two half anions, each
      with the N atom on a twofold axis, and approximately one fifth of a water
      molecule. The general anion departs significantly from the usual conformation: it
      lacks one of the typical 'W'-shaped sequence of O-S-N-S-O atoms. The compound
      also crystallizes in the solvent-free form, (II), in the space group P2(1)/c,
      with one formula unit in the asymmetric unit. Both compounds form ribbons of
      hydrogen-bonded cation dimers parallel to the b axis. In (I), there are two
      independent ribbons of opposite chirality, each involving one anion on a special
      position, and these ribbons are connected by hydrogen bonds to the anion on a
      general position, resulting in a layer structure parallel to (100). In (II), the
      chains are connected by hydrogen bonds, and again a layer structure parallel to
      (100) results.

PMID- 21727636
TI  - Two hydration products of 3,4,5,6-tetrachloro-N-(methyl-2-pyridyl)phthalmic
      acids.
AB  - In 2-amino-6-methylpyridin-1-ium 2-carboxy-3,4,5,6-tetrachlorobenzoate,
      C(6)H(9)N(2)(+).C(8)HCl(4)O(4)(-), there are two perpendicular chains of hydrogen
      bonded ions, one arising from the interaction between 2-carboxy-3,4,5,6
      tetrachlorobenzoate ions and the other from the interaction between the 2-amino-6
      methylpyridin-1-ium and 2-carboxy-3,4,5,6-tetrachlorobenzoate ions. These chains
      combine to form a two-dimensional network of hydrogen-bonded ions. Cocrystals of
      bis(2-amino-3-methylpyridin-1-ium) 3,4,5,6-tetrachlorophthalate-3,4,5,6
      tetrachlorophthalic acid (1/1), 2C(6)H(9)N(2)(+).C(8)Cl(4)O(4)(2
      ).C(8)H(2)Cl(4)O(4), form finite aggregates of hydrogen-bonded ions. pi-pi
      interactions are observed between 2-amino-3-methylpyridin-1-ium cations. Both
      structures exhibit the characteristic R(2)(2)(8) motif as a result of the
      hydrogen bonding between the 2-aminopyridinium and carboxylate units.

PMID- 21727637
TI  - Proton-transfer compounds of isonipecotamide with the aromatic dicarboxylic acids
      4-nitrophthalic, 4,5-dichlorophthalic, 5-nitroisophthalic and terephthalic acid.
AB  - The structures of the 1:1 proton-transfer compounds of isonipecotamide
      (piperidine-4-carboxamide) with 4-nitrophthalic acid [4-carbamoylpiperidinium 2
      carboxy-4-nitrobenzoate, C(6)H(13)N(2)O(8)(+).C(8)H(4)O(6)(-), (I)], 4,5
      dichlorophthalic acid [4-carbamoylpiperidinium 2-carboxy-4,5-dichlorobenzoate,
      C(6)H(13)N(2)O(8)(+).C(8)H(3)Cl(2)O(4)(-), (II)] and 5-nitroisophthalic acid [4
      carbamoylpiperidinium 3-carboxy-5-nitrobenzoate,
      C(6)H(13)N(2)O(8)(+).C(8)H(4)O(6)(-), (III)], as well as the 2:1 compound with
      terephthalic acid [bis(4-carbamoylpiperidinium) benzene-1,2-dicarboxylate
      dihydrate, 2C(6)H(13)N(2)O(8)(+).C(8)H(4)O(4)(2-).2H(2)O, (IV)], have been
      determined at 200 K. All salts form hydrogen-bonded structures, viz. one
      dimensional in (II) and three-dimensional in (I), (III) and (IV). In (I) and
      (III), the centrosymmetric R(2)(2)(8) cyclic amide-amide association is found,
      while in (IV) several different types of water-bridged cyclic associations are
      present [graph sets R(4)(2)(8), R(4)(3)(10), R(4)(4)(12), R(3)(3)(18) and
      R(6)(4)(22)]. The one-dimensional structure of (I) features the common 'planar'
      hydrogen 4,5-dichlorophthalate anion, together with enlarged cyclic R(3)(3)(13)
      and R(4)(3)(17) associations. In the structures of (I) and (III), the presence of
      head-to-tail hydrogen phthalate chain substructures is found. In (IV), head-to
      tail primary cation-anion associations are extended longitudinally into chains
      through the water-bridged cation associations, and laterally by piperidinium
      carboxylate N-H...O and water-carboxylate O-H...O hydrogen bonds. The structures
      reported here further demonstrate the utility of the isonipecotamide cation as a
      synthon for the generation of stable hydrogen-bonded structures. An additional
      example of cation-anion association with this cation is also shown in the
      asymmetric three-centre piperidinium-carboxylate N-H...O,O' interaction in the
      first-reported structure of a 2:1 isonipecotamide-carboxylate salt.

PMID- 21727638
TI  - Different cyclic motifs in phosphoric triamides containing a C(O)NHP(O)(NH)2
      skeleton and an R(2)(2)(10) graph set in three new compounds: a database analysis
      of hydrogen-bond strengths based on motifs.
AB  - In the crystal networks of N,N'-bis(2-chlorobenzyl)-N''-(2,6
      difluorobenzoyl)phosphoric triamide, C(21)H(18)Cl(2)F(2)N(3)O(2)P, (I), N-(2,6
      difluorobenzoyl)-N',N''-bis(4-methoxybenzyl)phosphoric triamide,
      C(23)H(24)F(2)N(3)O(4)P, (II), and N-(2-chloro-2,2-difluoroacetyl)-N',N''-bis(4
      methylphenyl)phosphoric triamide, C(16)H(17)ClF(2)N(3)O(2)P, (III), C=O...H
      N(C(O)NHP(O)) and P=O...H-N(amide) hydrogen bonds are responsible for the
      aggregation of the molecules. This is the opposite result from that commonly
      observed for carbacylamidophosphates, which show a tendency for the phosphoryl
      group, rather than the carbonyl counterpart, to form hydrogen bonds with the NH
      group of the C(O)NHP(O) skeleton. This hydrogen-bond pattern leads to cyclic
      R(2)(2)(10) motifs in (I)-(III), different from those found for all previously
      reported compounds of the general formula RC(O)NHP(O)[NR(1)R(2)](2) with the syn
      orientation of P=O versus NH [R(2)(2)(8)], and also from those commonly observed
      for RC(O)NHP(O)[NHR(1)](2) [a sequence of alternate R(2)(2)(8) and R(2)(2)(12)
      motifs]. In these cases, the R(2)(2)(8) and R(2)(2)(12) graph sets are formed
      through similar kinds of hydrogen bond, i.e. a pair of P=O...H-N(C(O)NHP(O))
      hydrogen bonds for the former and two C=O...H-N(amide) hydrogen bonds for the
      latter. This article also reviews 102 similar structures deposited in the
      Cambridge Structural Database and with the International Union of
      Crystallography, with the aim of comparing hydrogen-bond strengths in the above
      mentioned cyclic motifs. This analysis shows that the strongest N-H...O hydrogen
      bonds exist in the R(2)(2)(8) rings of some molecules. The phosphoryl and
      carbonyl groups in each of compounds (I)-(III) are anti with respect to each
      other and the P atoms are in a tetrahedral coordination environment. In the
      crystal structures, adjacent molecules are linked via the above-mentioned
      hydrogen bonds in a linear arrangement, parallel to [010] for (I) and (III) and
      parallel to [100] for (II). Formation of the N(C(O)NHP(O))-H...O=C instead of the
      N(C(O)NHP(O))-H...O=P hydrogen bond is reflected in the higher N(C(O)NHP(O))-H
      vibrational frequencies for these molecules compared with previously reported
      analogous compounds.

PMID- 21727639
TI  - Comparative sequence, antigenic and phylogenetic analysis of avian influenza
      (H9N2) surface proteins isolated in Pakistan between 1999 and 2008.
AB  - INTRODUCTION: Influenza A viruses possess a unique genomic structure which leads
      to genetic instability, especially in products of neuraminidase and hemagglutinin
      genes. These surface proteins play major roles in viral entry and release, and in
      the activation of the host immune system. METHODOLOGY: This study involved an in
      silico sequence, phylogenetic and antigenic analyses of hemagglutinin and
      neuraminidase proteins of avian influenza A (H9N2) strains that circulated in
      Pakistan's poultry flocks from 1999 to 2008 and determined variations among these
      sequences at different levels. RESULTS: Sequence and phylogenetic analysis
      revealed a large number of similar substitution mutations and close evolutionary
      relation among sequences of both proteins. Changes were observed in the N
      glycosylation sites of both surface proteins, along with the appearance of a new
      glycosylation site in the neuraminidase sequence isolated in 2007. Epitopes for
      hemagglutinin remained conserved, whereas for neuraminidase, epitopes from older
      strains reappeared in present sequences. CONCLUSIONS: Because of the rapid
      mutating nature of avian influenza subtype H9N2, constant surveillance of annual
      sequence variations is important. Preventive measures and vaccine products can be
      evaluated by keeping track of changes that may lead to reassortment among
      different circulating strains in Pakistan's commercial poultry flocks or in
      humans.

PMID- 21727640
TI  - Enteroaggregative E. coli O104 from an outbreak of HUS in Germany 2011, could it
      happen again?
AB  - Enterohaemorrhagic E. coli (EHEC) particularly O157:H7 (Sequence type 11
      complex), is the best documented and most well-known of E. coli that cause
      diarrhoea. The importance of EHEC lies in the severity of disease. Outbreaks can
      infect thousands of people causing bloody diarrhoea and haemolytic uremic
      syndrome (HUS) that in turn can result in protracted illness or even death. The
      ability of EHEC to colonise the human gut is normally associated with the
      presence of genes from another group of diarrhoeagenic E. coli, the
      enteropathogenic E. coli (EPEC), via the locus of enterocyte effacement. However,
      the massive outbreak in Germany was caused by an EHEC which had acquired
      virulence genes from yet another group of diarrhoeagenic E. coli, the
      enteroaggregative E. coli (EAEC). In reality EAEC is probably the most common
      bacterial cause of diarrhoea but is not identified in most diagnostic
      laboratories. This outbreak emphasises the importance of being able to detect all
      diarrhoeagenic E. coli and not to focus on E. coli O157:H7 alone. Routine
      surveillance systems for EAEC, a once ignored global pathogen, would go a long
      way to reaching this goal. This review describes methods for identifying non-O157
      EHEC and describes the key genetic features of EHEC and EAEC. Our aim is to
      provide information for laboratories and policy makers which enables them to make
      informed decisions about the best methods available for detecting newly emergent
      strains of diarrhoeagenic E. coli.

PMID- 21727641
TI  - Escherichia coli (STEC) serotype O104 outbreak causing haemolytic syndrome (HUS)
      in Germany and France.
AB  - At the beginning of May an outbreak of bloody diarrhoea and haemolytic uraemic
      syndrome (HUS) began in Germany. During the succeeding months following the
      initial outbreak in Germany, thousands of infections occurred resulting in 877
      cases of haemolytic uraemic syndrome (HUS) with 32 deaths and 3,043 cases of
      enterohaemorrhagic Escherichia coli (EHEC) with 16 deaths.

PMID- 21727642
TI  - Outbreak of Chikungunya in the Republic of Congo and the global picture.
AB  - Chikungunya fever is a crippling disease caused by an arthropod-borne virus
      (arbovirus) transmitted to humans through mosquitoes. Although Chikungunya virus
      is not often associated with mortality, the effects of virus outbreaks are often
      devastating, causing significant economic loss due to the strain on health care.
      Chikungunya is quickly spreading globally as a result of viral genetic mutations
      leading to the adaptation of new vector hosts and insecticide resistance. The
      recent outbreak of Chikungunya fever in the republic of Congo has reported
      thousands of people affected. Here we review the past Chikungunya fever
      epidemiology and new reports aimed at therapeutic intervention of this disease.

PMID- 21727643
TI  - Device-associated infections rates in pediatrics and neonatal intensive care
      units in El Salvador: findings of the INICC.
AB  - INTRODUCTION: This study aimed to determine the rate of device-associated, health
      care-associated infection (DA-HAI), the excess in length of stay, the mortality,
      and the hand hygiene compliance in a pediatric intensive care unit (PICU) and a
      neonatal ICU (NICU) in a hospital member of the International Infection Control
      Consortium (INICC) in El Salvador. METHODOLOGY: A prospective cohort, active DA
      HAI surveillance study was conducted on patients admitted in the pediatric and
      neonatal ICUs from January 2007 to November 2009. The protocol and methodology
      implemented were developed by INICC. Data were collected in the participating
      ICUs, and analyzed at INICC headquarters by proprietary software. DA-HAI rates
      were recorded by applying the definitions of the Centers for Disease Control and
      Prevention National Healthcare Safety Network. RESULTS: Of 1,145 patients
      hospitalized in the PICU for 9,517 days, 177 acquired DA-HAIs (overall rate
      15.5%), and 18.6 DA-HAIs per 1,000 ICU-days. Furthermore, 1,270 patients
      hospitalized in the NICU for 30,663 days acquired 302 DA-HAIs (overall rate
      23.8%), and 9.8 DA-HAIs per 1,000 ICU-days. The central line-associated
      bloodstream infection (CLA-BSI) rates in the NICU and PICU were 9.9 and 10.0 per
      1,000 catheter-days respectively. The ventilator-associated pneumonia (VAP) rate
      was 16.1 per 1,000 ventilator-days in the NICU and 12.1 in the PICU.The catheter
      associated urinary tract infection (CAUTI) rate was 5.8 per 1,000 catheter-days
      in the PICU. CONCLUSIONS: DA-HAI rates in the PICU and NICU of our hospital were
      higher than international standards; infection control programs including
      surveillance and antibiotic policies must be a priority in El Salvador. 

PMID- 21727644
TI  - Intravascular catheter-related infections in an Indian tertiary care hospital.
AB  - INTRODUCTION: This study had two objectives: 1) to determine the clinical and
      microbiological profiles of patients developing intravascular catheter-related
      local (localized catheter colonization and exit site) and systemic infections and
      their predisposing factors; 2) to study the antibiotic sensitivity patterns of
      the organisms isolated. METHODOLOGY: This case-control study was conducted over
      19 months involving 232 patients at a tertiary care hospital. Non-tunneled
      central venous catheters and midline catheters were the two types studied.
      Catheter tips were processed using Maki's roll plate and endoluminal flush
      techniques. Blood cultures were drawn under strict aseptic precautions and
      processed by the BacT ALERT system. A "case" was any patient with proven
      localized catheter colonization, exit site infection or blood-stream infection
      and a "control" was any patient from whom the intravascular catheter yielded no
      organism in semi-quantitative cultures. RESULTS AND CONCLUSIONS: The incidence of
      catheter-related blood-stream infections (CRBSI) in our institute was 8.75 per
      1,000 catheter days. The commonest organisms causing local infections were
      coagulase-negative Staphylococci, and those causing CRBSI were Staphylococcus
      aureus. Multidrug-resistant organisms accounted for 30.2% of the infections. Risk
      factors for development of catheter-related infections included an immune
      compromised state, duration of the catheter in situ, femoral venous cannulation,
      and triple lumen catheters. Choice of venous cannulation to minimize the risk of
      catheter-related infection in ascending order for risk of infection is the
      subclavian vein, jugular vein, basilic vein and then the femoral vein. There was
      no role for empirical antibiotic therapy to prevent intravascular catheter
      related local or systemic infections. 

PMID- 21727645
TI  - The presence of Mycoplasma pneumoniae infection and GM1 ganglioside antibodies in
      Guillain-Barre syndrome.
AB  - INTRODUCTION: Guillain-Barre syndrome (GBS) is an autoimmune disorder affecting
      the peripheral nervous system, usually triggered by an acute infection. GBS
      patients are known to have antecedent bacterial infections associated with auto
      antibodies to various gangliosides. This investigation aimed to evaluate GBS
      patients for serological evidence of Mycoplasma pneumoniae infection and anti GM1
      ganglioside antibodies. METHODOLOGY: This cross-sectional study included 57
      pediatric GBS patients, 42 neurological controls (i.e., non-GBS Acute Flaccid
      Paralysis cases) and 35 non-neurological controls. Enzyme linked immune sorbent
      assay (ELISA) was performed on the sera of the subjects to detect IgM and IgG
      antibodies against Mycoplasma (M.) pneumoniae and GM1 gangliosides. RESULTS: The
      results showed that 15.79% and 21.05% GBS patients were positive for IgG and IgM
      antibodies against M. pneumoniae as compared to 2.38% (P < 0.05) and 14.2% in non
      GBS-AFP and 5.7% and 14.2% in non-neurological controls respectively.
      Additionally, 43.85% and 38.54% GBS patients were positive for IgG and IgM
      antibodies against GM1 gangliosides as compared to 38.09% and 28.57% in non-GBS
      AFP and 14.2% and 2.84% in non-neurological controls respectively (P < 0.05).
      CONCLUSIONS: Significant difference in levels of IgG antibodies against M.
      pneumoniae was observed between GBS patients and neurological controls,
      suggesting M. pneumoniae to be an important antecedent to GBS. Significant
      difference in levels of anti GM1 ganglioside antibodies (IgG & IgM) was seen
      between GBS patients and non-neurological controls, highlighting its possible
      role in the pathogenesis of GBS.

PMID- 21727646
TI  - Phylogenetic relationship of Salmonella enterica strains in Tehran, Iran, using
      16S rRNA and gyrB gene sequences.
AB  - INTRODUCTION: We assessed whether 16S rDNA and gyrB gene sequences, alone or
      combined, were suitable for determining the phylogenetic relationship among
      Salmonella enterica strains isolated from Tehran, Iran. Patients over five years
      of age enrolled in an acute diarrheal surveillance project in Tehran province
      between May 2004 and October 2006 were selected as our study group. METHODOLOGY:
      16S ribosomal DNA (rDNA) and gyrB genes from 40 Salmonella isolates obtained from
      patients with acute diarrhea were sequenced and the data was used to generate
      phylogenetic trees that facilitated isolate comparison. RESULTS: Salmonella
      strains clustered into five to seven phylogenetic groups, dependent on analysis
      of 16S rDNA (1546 bp), gyrB (1256 bp) or a combination of the two genes. By 16S
      rDNA sequence analysis, only strains of Salmonella enterica serovar Typhi ( S.
      Typhi) clustered exclusively together. gyrB sequences permitted clustering of all
      the S. Typhi and S. Paratyphi A isolates, and clustering of S. Enteritidis into
      two separate but exclusive groups. Concatenation of the two data sets did not
      significantly improve the resolution of the strains compared to the gyrB gene.
      None of the analyses completely resolved S. enterica Paratyphi B and C into
      mutually exclusive groups. CONCLUSION: Sequencing of gyrB represents a
      potentially useful tool for determining the phylogenetic relationship of S.
      enterica strains in Tehran, Iran. Genetic analysis of the 16S rRNA gene alone or
      in combination with gyrB did not increase the resolution between serotypes of S.
      enterica. We speculate that inclusion of additional genetic markers would improve
      the sensitivity of the analysis.

PMID- 21727647
TI  - Analysis of interleukin-10 gene polymorphisms and hepatitis C susceptibility in
      Pakistan.
AB  - INTRODUCTION: Hepatitis C virus (HCV) commonly causes a chronic infection but few
      of patients are able to clear the virus naturally. Interleukin-10 (IL-10) is an
      anti-inflammatory cytokine that can suppress the immune response against HCV.
      Interindividual variations in IL-10 production are genetically contributed by
      polymorphisms within the IL-10 promoter region. This study aimed to investigate
      the association of the IL-10 gene promoter -1082 G/A, -819 C/T, and -592 C/A
      polymorphisms with HCV infection susceptibility in Pakistani individuals.
      METHODOLOGY: Eighty-nine chronically infected patients and 99 controls were
      enrolled in the study. IL-10 (-1,082 G/A, -819 C/T, -592 C/A) genotyping was
      performed by amplification refractory mutation system-polymerase chain reaction
      (ARMS-PCR). RESULTS: A suggestive evidence of association with hepatitis C was
      obtained for the IL-10 -819 C/T (-592 C/A) (p: 0.03) promoter polymorphism at the
      allele level  but not in genotype distribution. The IL-10 -1082 allele showed no
      association while positive association of GG (p: 0.001) gene and negative
      association for GA (0.001) gene were observed.  Higher frequencies were observed
      for GTA (p: 0.02), ACC (p: 0.01) haplotype and GCC/GTA (p: 0.005) diplotype in
      HCV patients than controls while diplotype GCC/ATA showed protective effect
      against HCV. CONCLUSIONS: Our findings suggest that different IL-10 gene
      polymorphisms may lead to an imbalance between the pro-inflammatory and anti
      inflammatory cytokine responses which may in turn influence the susceptibility to
      HCV infection.

PMID- 21727648
TI  - Identification of feline immunodeficiency virus subtype-B on St. Kitts, West
      Indies by quantitative PCR.
AB  - INTRODUCTION: Although antibodies to the feline immunodeficiency virus (FIV) have
      been detected by SNAP assay in cats from St. Kitts, there have been no molecular
      studies to further confirm the infection and determine the FIV subtypes present.
      METHODOLOGY: Total nucleic acids were extracted from EDTA whole blood specimens
      from 35 cats, followed by quantitative fluorescence resonance energy transfer
      (FRET) PCR under a six-channel LightCycler 2.0 Instrument with Software version
      4.1. RESULTS: Four of 11 stray cats (36 %) but none of 24 owned cats were FIV
      positive by real-time PCR.  High-resolution melting curve analysis indicated that
      all four positive cats were infected with FIV subtype-B. CONCLUSIONS: This is the
      first molecular characterization of FIV subtypes on St. Kitts and the results
      confirm the high prevalence of FIV infection in stray cats on the island.

PMID- 21727649
TI  - Human T Lymphotropic virus-1 associated gastrointestinal histoplasmosis in Peru.
AB  - We report a 72-year-old patient with chronic diarrhoea and histologic evidence of
      gastrointestinal histoplasmosis. He had no history of HIV or of taking
      immunosuppressive drugs. The patient was found to be a carrier of Human T
      lymphotropic virus-1, a condition associated with inflammatory,
      lymphoproliferative, and opportunistic infectious diseases. To our knowledge,
      there are only three previous cases reporting this coinfection and this is the
      first documented case with gastrointestinal involvement.

PMID- 21727650
TI  - Neonatal Plasmodium vivax malaria: an overlooked entity.
AB  - Although malaria is endemic in India, neonatal disease is considered rare. We
      report a case of neonatal malaria in a 26-day-old neonate with fever and
      splenomegaly who was diagnosed after a long and unsuccessful battery of tests for
      splenomegaly. Routine screening for malaria is essential for all neonates with
      fever in endemic areas. Early diagnosis and treatment of malaria could
      effectively prevent infant mortality.

PMID- 21727651
TI  - Saccharomyces cerevisiae oesophagitis in a patient with oesophageal carcinoma.
AB  - Saccharomyces species are emerging opportunistic fungal pathogens that can cause
      bloodstream infections in humans. These infections have often been associated
      with the ingestion of probiotics. Saccharomyces oesophagitis is a rare condition
      which has been described so far in only two publications. Here we report the case
      of a patient who was diagnosed with Saccharomyces oesophagitis. The clinical
      picture was indistinguishable from that of Candida oesophagitis. The
      Saccharomyces isolate was shown to be susceptible to fluconazole by both CLSI M27
      A and disk diffusion methods. In contrast to cases of fungaemia, Saccharomyces
      oesophagitis does not seem to follow probiotic use. Due to the potential for
      antifungal resistance among emerging fungal pathogens, proper mycological
      identification at the species level is essential.

PMID- 21727652
TI  - Plasmid-mediated quinolone resistance by genes qnrA1 and qnrB19 in Salmonella
      strains isolated in Brazil.
AB  - Considering the importance of the mechanisms involved in quinolone resistance,
      this study evaluate the presence of PMQR in 126 epidemic and not epidemic strains
      of Salmonella spp. It was noted that presence of PMQR, by itself, did not
      generate resistance to ciprofloxacin; but detection of qnr genes in Salmonella
      spp. and the identification of the qnrB19 variant in a strain of poultry origin
      alert for the indiscriminate use of quinolones in poultry production, that can
      result in a pressure for mutant selection of resistant strains with a clinical
      limitation use of FQs in the near future. And last but not least, is the need to
      continued study of resistance mechanisms and to monitor the microbial resistance
      profile of epidemiological strains.

PMID- 21727653
TI  - Isolation frequency and susceptibility patterns of Nocardia species at a tertiary
      hospital laboratory in Karachi, Pakistan.

PMID- 21727654
TI  - More blood, more life? Reflections on World Blood Donor Day-2011.

PMID- 21727655
TI  - Association of gene polymorphisms with development of cancer risk or their
      protective role associated with some mutant alleles.

PMID- 21727656
TI  - Endometriosis, a modern syndrome.
AB  - The identification of endometriosis has been a subject of intense debate over the
      last decade. There is, however, no doubt that Thomas Cullen was the first to
      describe endometriosis and adenomyosis as one disease characterized by the
      presence of endometrium-like tissue outside the uterine cavity. With the
      introduction of laparoscopy in the early 1960s three different clinical
      presentations of endometriosis were distinguished: peritoneal, deep adenomyotic
      and cystic ovarian. As soon as synthetic steroids became available, pioneer
      clinicians started utilizing these in an attempt to replace radical surgery by a
      medical treatment. While medical therapy may resort in relief, in most cases the
      current approach consists of a combination of medical and surgical therapy. While
      the pathogenesis of endometriosis is still enigmatic and complex, there is
      increasing evidence that endometriosis is part of a uterine reproductive
      dysfunction syndrome. For prevention of complications, it is very important that
      diagnosis is made as early as possible in a woman's life.

PMID- 21727657
TI  - Club drugs: review of the 'rave' with a note of concern for the Indian scenario.
AB  - 'Club drugs' which include Ecstasy, gamma-hydroxybutyrate (GHB), ketamine, and
      Rohypnol (flunitrazepam) have become popular with participants in 'raves',
      because they are perceived to enhance energy, endurance, sociability and sexual
      arousal. These drugs vary in their pharmacologic properties, physiological and
      psychological effects, and potential consequences. The use of club drugs by young
      people has increased in the last decade, and continue to get modified and evolve,
      making them very difficult to monitor. Further, these drugs are not picked up by
      routine drugs screening procedures, thereby making these popular with the
      criminals. India, which is in a phase of social transition, also faces this
      rising menace. Despite the nature and extent of this problem, this area has been
      under-researched. Data from India are sparse barring a few newspaper and police
      reports. Keeping abreast of current trends in club drug use prepares the
      clinician to recognize the clinical effects of club drug use, to manage club drug
      related emergencies, and to generate social awareness.

PMID- 21727658
TI  - Protective association exhibited by the single nucleotide polymorphism (SNP)
      rs1052133 in the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of
      squamous cell carcinomas of the head & neck (SCCHN) among north Indians.
AB  - BACKGROUND & OBJECTIVES: Imbalances in compactly regulated DNA repair pathways in
      the form of single nucleotide polymorphisms (SNPs) within vital DNA repair genes
      may result in insufficient DNA repair and increase in DNA breaks thus rendering
      the human system vulnerable to the debilitatory effects of grave diseases like
      cancers. The present study involves investigation of association of the non
      synonymous SNP rs1052133 (C8069G/Ser326Cys) located in the exonic region of the
      gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell
      carcinomas of the head and neck (SCCHN). METHODS: Case-control based genetic
      association study was performed among 575 (250 SCCHN cases and 325 normal healthy
      controls) sub-population cluster-matched (Indo-Europeans linguistic subgroup +
      Caucasoid morphological subtype) samples from the north Indian States of Uttar
      Pradesh and Uttarakhand using polymerase chain reaction followed by restriction
      fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis. RESULTS: Our
      results demonstrated statistically significant protective association for the
      heterozygous CG [Odds Ratio (OR) 0.6587, 95% Confidence Interval (CI) 0.4615 to
      0.9402, P=0.0238], homozygous mutant GG (OR 0.2570, 95% CI 0.1070 to 0.6175,
      P=0.0013) and combined mutant CG + GG (OR 0.6057, 95% CI 0.4272 to 0.8586,
      P=0.0059) genotypes. INTERPRETATION & CONCLUSIONS: The results indicate that the
      polymorphism rs1052133 is strongly associated with SCCHN susceptibility and the
      mutant (G) allele might be a protective factor for SCCHN among north Indian
      subpopulations.

PMID- 21727659
TI  - Pulmonary tuberculosis among health care workers at two designated DOTS Centers
      in urban city of Ibadan, Nigeria.
AB  - BACKGROUND & OBJECTIVES: Tuberculosis (TB) infection control interventions are
      not routinely implemented in many Sub-Saharan African countries including
      Nigeria. This study was carried out to ascertain the magnitude of occupationally
      acquired pulmonary TB (PTB) among health care workers (HCWs) at two designated
      DOTS centers in Ibadan, Nigeria. METHODS: One year descriptive study (January
      December 2008) was carried out at the University College Hospital and Jericho
      Chest Hospital, both located in Ibadan, Nigeria. A pre-tested questionnaire was
      used to obtain socio-demographic data and other relevant information from the
      subjects. Three sputum samples were collected from each subject. This was
      processed using Zeihl-Neelsen (Z-N) stains. One of the sputum was cultured on
      modified Ogawa egg medium incubated at 37  degrees  C for six weeks.
      Mycobacterium tuberculosis was confirmed by repeat Z-N staining and biochemical
      tests. RESULTS: A total of 271 subjects, 117 (43.2%) males and 154 (56.8%)
      females were studied. Nine (3.3%) had their sputum positive for acid fast bacilli
      (AFB) while six (2.2%) were positive for culture. The culture contamination rate
      was 1.8 per cent. Significantly, all the six culture positive samples were from
      males while none was obtained from their female counterparts. About half of the
      AFB positive samples were from subjects who have spent five years in their
      working units. Eight AFB positive cases were from 21-50 yr age group while
      students accounted for seven AFB positive cases. INTERPRETATION & CONCLUSIONS:
      The study shows that occupationally-acquired PTB is real in Ibadan. Further
      studies are needed to ascertain and address the magnitude of the problem.

PMID- 21727660
TI  - Molecular typing of Mycobacterium leprae strains from northern India using short
      tandem repeats.
AB  - BACKGROUND & OBJECTIVES: Due to the inability to cultivate Mycobacterium leprae
      in vitro and most cases being paucibacillary, it has been difficult to apply
      classical genotyping methods to this organism. The objective of this study was
      therefore, to analyze the diversity among M. leprae strains from Uttar Pradesh,
      north India, by targeting ten short tandem repeats (STRs) as molecular markers.
      METHODS: Ninety specimens including 20 biopsies and 70 slit scrappings were
      collected in TE buffer from leprosy patients, who attended the OPD of National
      JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, and
      from villages of Model Rural Health Research Unit (MRHRU) at Ghatampur, Kanpur,
      Uttar Pradesh. DNA was extracted from these specimens and ten STRs loci were
      amplified by using published and in-house designed primers. The copy numbers were
      determined by electrophoretic mobility as well as sequence analysis. Phylogenetic
      analysis was done on variable number of tandem repeats (VNTRs) data sets using
      start software. RESULTS: Diversity was observed in the cross-sectional survey of
      isolates obtained from 90 patients. Allelic index for different loci was found to
      vary from 0.7 to 0.8 except for rpoT for which allelic index was 0.186.
      Similarity in fingerprinting profiles observed in specimens from the cases from
      same house or nearby locations indicated a possible common source of infection.
      Such analysis was also found to be useful in discriminating the relapse from
      possible reinfection. INTERPRETATION & CONCLUSIONS: This study led to
      identification of STRs eliciting polymorphism in north Indian strains of M.
      leprae. The data suggest that these STRs can be used to study the sources and
      transmission chain in leprosy, which could be very important in monitoring of the
      disease dynamics in high endemic foci.

PMID- 21727661
TI  - Smoking cessation support in Iran: availability, sources & predictors.
AB  - BACKGROUND & OBJECTIVES: Smoking cessation advice is known as an important factor
      in motivating smokers to quit smoking. We investigated the extent, sources and
      predictors of receiving unsolicited advice and seeking active advice for smoking
      cessation in Iran. METHODS: A cross-sectional study was performed as a part of
      Isfahan Healthy Heart Program (IHHP) on 9093 adult individuals (both men and
      women) in 2004-2005. Demographic characteristics, smoking status, sources and
      preferences for smoking cessation support were recorded. RESULTS: In the studied
      population, 66.8 and 14.4 per cent had received and asked for cessation support,
      respectively. Smokers had received advice from family (92.2%), friends (48.9%),
      physician (27.9%) and other health care providers (16.2%). Smokers had asked for
      cessation help more frequently from family (64.5%) and friends (42.0%). Women
      (OR: 0.59, 95% CI: 0.37-0.94) and singles (OR: 0.51, 95% CI: 0.36-0.71) received
      less advice. Hookah smokers received (OR: 0.23; 95% CI: 0.14-0.38) and asked (OR:
      0.21; 95% CI: 0.06-0.68) for cessation help less than cigarette smokers.
      Receiving advice increased the odds of seeking support (OR: 7.98; 95% CI: 4.37
      14.57). INTERPRETATION & CONCLUSIONS: Smokers' family and friends were more
      frequent sources for smoking cessation support. Tobacco control programmes can
      count on smokers' family and friends as available sources for smoking cessation
      support in countries where smoking cessation counselling services are less
      available. However, the role of physicians and health care workers in the smoking
      cessation counselling needs to be strengthened.

PMID- 21727662
TI  - Evaluation of effect of isoflavone on thyroid economy & autoimmunity in
      oophorectomised women: a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: The potential of soy isoflavones to interfere with
      thyroid function has been reported. However, there are limited data regarding
      their effect on thyroid function and autoimmunity in surgical menopausal women.
      The present study aimed to evaluate the effect of isoflavones on thyroid function
      and autoimmunity, menopausal symptoms, serum follicle stimulating hormone (FSH)
      and estradiol levels in oophorectomised women. METHODS: A randomized, double
      blind, placebo-controlled trial was conducted in 43 oophorectomised women to
      evaluate the effect of soy isoflavones (75 mg/day for 12 wk) on serum thyroid
      profile (free T3, free T4, TSH, TBG and anti-TPO antibody titres) assessed at
      baseline, 6 and 12 wk after randomization. Assessment was also done for menopause
      symptom score (MSS) three weekly, and FSH and estradiol levels at baseline and at
      study completion. RESULTS: There was a significant alteration in free T3 levels
      in the group receiving isoflavones (4.05 +/- 0.36, 4.12 +/- 0.69 and 3.76 +/-
      0.55 pmol/l at baseline, 6 and 12 wk, respectively; P=0.02). However, the mean
      change in various thyroid parameters at 12 wk from baseline was not significantly
      different between the two groups. MSS was also significantly decreased at 9 and
      12 wk from baseline with isoflavones (12.47 +/- 8.15, 9.35 +/- 5.23 and 9 +/-
      5.14 at baseline, 9 and 12 wk respectively; P=0.004) with significant improvement
      in urogenital symptoms compared to placebo. Isoflavones did not significantly
      affect other parameters during study period. There were no serious adverse events
      reported and the proportion of patients experiencing adverse events was similar
      between the two groups. INTERPRETATION AND CONCLUSIONS: Modest reduction in serum
      free T3 levels in the isoflavone group in the absence of any effect on other
      thyroid parameters might be considered clinically unimportant.

PMID- 21727663
TI  - Quality of life after electroconvulsive therapy in persons with treatment
      resistant schizophrenia.
AB  - BACKGROUND & OBJECTIVES: In recent years, health-related quality of life (QOL)
      has been regarded as the most important dimension of outcome in schizophrenia.
      Recent research has shown that atypical antipsychotics improve QOL in patients
      with schizophrenia. Importance of electroconvulsive therapy (ECT) has been
      demonstrated in restoring function and health related quality of life in
      depressed patients. However, there are no data on patients of schizophrenia. The
      objective of the present study was therefore, to assess the improvement in
      quality of life after ECT in treatment resistant schizophrenia. METHODS: Thirty
      consecutive patients of treatment resistant schizophrenia were given ECT sessions
      twice a week and assessments were made with Positive and Negative Syndrome Scale
      of Schizophrenia (PANSS), WHO QOL Bref, Global Assessment of Functioning Scale
      and Clinical Global Impressions. RESULTS: The group improved significantly on all
      the domains of quality of life scale except the domain named satisfaction with
      social relations. There was also significant change in the total score of PANSS
      after 6 ECT sessions (mean at baseline = 86.7, mean after 6 ECT = 65.5, P< 0.001)
      as well as on different subscales of PANSS. The score on the global assessment of
      functioning also changed significantly (mean 26.3 at baseline to 44.5 after 6 ECT
      sessions). INTERPRETATION & CONCLUSIONS: The present findings showed that ECT in
      addition to improvement in symptomatology led to improvement in QOL in patients
      of treatment resistant schizophrenia.

PMID- 21727664
TI  - Validation of bedside methods in evaluation of diabetic peripheral neuropathy.
AB  - BACKGROUND & OBJECTIVES: Vibration perception threshold (VPT) is considered as a
      gold standard for diagnosis of diabetic peripheral neuropathy. However, the data
      are sparse comparing the VPT with commonly used bedside modalities. This study
      was carried out to evaluate the usefulness of simple bed side screening
      modalities for peripheral neuropathy in patients with diabetes mellitus. METHODS:
      A total of 1044 patients with diabetes mellitus attending the Diabetes clinic
      from January 2007 to May 2008, were included in this study. All subjects had a
      detailed clinical assessment including Diabetic Neuropathy Symptom (DNS) score,
      Diabetic Neuropathy Examination (DNE) score, ankle reflex, vibration sensation
      with a 128 Hz tuning fork, 10 g Semmes-Weinstein monofilament and vibration
      perception threshold (VPT). RESULTS: The prevalence of peripheral neuropathy was
      34.9 per cent with VPT. Foot care practices were followed by only 214 (20.5%) of
      the study population. When compared with VPT, ankle reflex was the most sensitive
      (90.7%) but least specific (37.3%). The tuning fork and monofilament tests
      respectively had lower sensitivity (62.5 and 62.8%) but better specificity (95.3
      and 92.9%) and accuracy (78.9 and 77.9%). Significant correlations were observed
      between the VPT score and the DNE (r = 0.532, P<0.001) and DNS (r = 0.546,
      P<0.001) scores and absent tuning fork sensation (r = 0.590; P<0.001),
      monofilament sensation (r = 0.573; P<0.001) and ankle reflex (r = 0.377, P =
      0.01). INTERPRETATION & CONCLUSIONS: The present findings show that simple bed
      side tests are useful for assessing peripheral diabetic neuropathy, even in those
      subjects in whom foot care practices are not followed.

PMID- 21727665
TI  - Development of a controlled release formulation of an indigenous insect growth
      regulator, DPE-28, a substituted diphenylether, for controlling the breeding of
      Culex quinquefasciatus.
AB  - BACKGROUND & OBJECTIVES: DPE-28, a substituted diphenyl ether (2,6
      ditertiarybutyl phenyl-2',4'-dinitro phenyl ether) was reported to exhibit
      promising insect growth regulating activity against Culex quinquefasciatus, the
      vector of lymphatic filariasis. A controlled release formulation (CRF) of DPE-28
      has been developed to control Cx. quinquefasciatus in its breeding habitats.
      Toxicity of DPE-28, safety to non-target mosquito predators and the release
      profile of the CRF of DPE-28 are studied and discussed. METHODS: The acute oral
      and dermal toxicity was tested in male and female Wistar rats as per the
      Organization for Economic Cooperation and Development (OECD) guidelines 425 and
      402 respectively. The toxicity of DPE-28 to non-target predators was tested as
      per the reported procedure from this laboratory. The CRF of DPE-28 was prepared
      by following the reported procedure developed at this laboratory earlier. The
      concentration of DPE-28 released from the CRF was monitored by HPLC by
      constructing a calibration graph by plotting the peak area in the Y-axis and the
      concentration of DPE-28 in the X-axis. RESULTS: DPE-28 has been tested for acute
      oral toxicity and found to be moderately toxic with LD 50 value of 1098 mg/kg
      body weight (b.w). The results of the acute dermal toxicity and skin irritation
      studies reveal that DPE-28 is safe and non-irritant. DPE-28 when tested at 0.4
      mg/litre against non-target mosquito predators did not produce any mortality. The
      release profile of the active ingredient DPE-28 from the CRF by HPLC technique
      showed that the average daily release (ADR) of DPE-28 ranged from 0.07 to 5.0
      mg/litre during first four weeks. Thereafter the matrix started eroding and the
      ADR ranged from 5 to 11 mg/litre during the remaining 5 wk. The cumulative
      release of active ingredient showed that > 90 per cent of the active ingredient
      was released from the matrix. INTERPRETATION & CONCLUSIONS: The controlled
      release matrix of DPE-28 was thus found to inhibit the adult emergence (>80%) of
      Cx. quinquefasciatus for a period of nine weeks. The CRF of DPE-28 may play a
      useful role in field and may be recommended for mosquito control programme after
      evaluating the same under field conditions.

PMID- 21727666
TI  - Seasonal prevalence & resting behaviour of Anopheles minimus Theobald & An.
      fluviatilis James (Diptera: Culicidae) in east-central India.
AB  - BACKGROUND & OBJECTIVES: Anopheles minimus has recently been reported to have re
      appeared in Keonjhar district of Orissa after a period of about 45 years of
      launching the malaria eradication programme. An. minimus and An. fluviatilis were
      the incriminated major malaria vectors in the district, endemic for falciparum
      malaria. The information on seasonal prevalence and resting behaviour of the
      vectors is crucial for implementing appropriate malaria control measures.
      Therefore, a study was undertaken on seasonal prevalence and resting behaviour of
      An. minimus and An. fluviatilis in this district. METHODS: Seven randomly
      selected villages of Keonjhar district, Orissa, were studied during August 2005
      to November 2007. Daytime resting collections indoors and outdoors were made
      covering three seasons of the year. The Anopheles mosquitoes obtained from
      different habitats were identified. Collections were maintained separately
      according to different sites as well as heights of the walls in human dwellings.
      RESULTS: Among the indoor collections, the densities of An. minimus and An.
      fluviatilis were higher in human dwellings than cattle sheds. An. fluviatilis was
      the predominant (41.5%) species followed by An. minimus (26.3%) in human
      dwellings. The density of both the vector species in human dwellings peaked
      during rainy and winter seasons followed by summer. Walls were the most preferred
      site by these vectors for resting and the maximum number was collected at a
      height of 3 to 4 ft. INTERPRETATION & CONCLUSIONS: The resting behaviour of the
      vector species increases their contact with the sprayed walls and therefore, a
      quality residual spraying of human dwellings focusing indoor walls could
      interrupt the malaria transmission in this area.

PMID- 21727667
TI  - Anaemia & expression levels of CD35, CD55 & CD59 on red blood cells in Plasmodium
      falciparum malaria patients from India.
AB  - BACKGROUND & OBJECTIVES: Severe anaemia in Plasmodium falciparum (Pf) associated
      malaria is a leading cause of death despite low levels of parasitaemia. In an
      effort to understand the pathogenesis of anaemia we studied expression level of
      RBC complement regulatory proteins, CR1 (CD35), CD55 and CD59 with haemoglobin
      status in a group of malaria cases from Assam, Goa and Chennai, and in healthy
      controls. METHODS: Flowcytometry was used to study expression of CR1, CD55 and
      CD59 in 50 Pf cases and 30 normal healthy volunteers. Giemsa stained thick and
      thin blood films were used for microscopic detection and identification of
      malarial parasites and parasite count. RESULTS: No correlation was found between
      degree of expression of RBC surface receptors CR1, CD55 and CD59 with haemoglobin
      level. However, expression of CD55 was less in malaria cases than in healthy
      controls. INTERPRETATION & CONCLUSIONS: The present findings indicate that
      malaria infection changes the expression profile of complement regulatory protein
      CD55 irrespective of severity status of anaemia. Further studies are needed to
      explore the pathophysiology of anaemia in malaria cases in Assam where expression
      of RBC complement receptors appears to be low even in normal healthy population.

PMID- 21727668
TI  - Malaria incidence among paramilitary personnel in an endemic area of Tripura.
AB  - BACKGROUND & OBJECTIVES: Paramilitary operations along the Indo-Bangladesh border
      are adversely affected by malaria induced morbidity and mortality. Villages
      surrounding the paramilitary installations often serve as disease reservoirs.
      Malaria incidence in Tripura State Rifles (TSR) units in Dhalai District of
      Tripura was studied and the role of the village population in disease
      transmission was also assessed. METHODS: Mass blood surveys were carried out
      among TSR personnel and villagers during 2007 to 2009. Malaria diagnosis through
      blood smear examination and rapid detection kits was done, and percentage
      parasitaemia was determined. Activity of malaria vectors was monitored using CDC
      light traps. RESULTS: Slide positivity rates (SPR) in the neighbouring villages
      (51.4%) was significantly higher than that in TSR (27.7%) (P<0.0001). Malaria
      incidence in villages did not show seasonal variability while it was lowest
      during post-monsoon season in TSR (P<0.325; OR = 0.74). Per cent Pf parasitaemia
      was high in TSR (0.29) as compared to villagers (0.20) (P<0.0001). Anopheles
      minimus and An. dirus were the major malaria vectors observed. INTERPRETATION &
      CONCLUSIONS: Paramilitary and public health authorities should adopt targeted
      measures to reduce the malaria incidence in the villages surrounding the
      paramilitary installations as the village populations play a major role in
      disease transmission.

PMID- 21727669
TI  - Entomological study of chikungunya infections in the State of Kelantan, Malaysia.
AB  - BACKGROUND & OBJECTIVES: Chikungunya infection has become a public health threat
      in Malaysia since the 2008 nationwide outbreaks. Aedes albopictus Skuse has been
      identified as the chikungunya vector in Johor State during the outbreaks. In
      2009, several outbreaks had been reported in the State of Kelantan. Entomological
      studies were conducted in Kelantan in four districts, namely Jeli, Tumpat, Pasir
      Mas and Tanah Merah to identify the vector responsible for the virus
      transmission. METHODS: CHIKV cases records were obtained from State Health
      Department, Kelantan and localities involved were identified. Larva survey was
      conducted to collect the immature mosquito stages. Modified aspirators were used
      to collect the adult mosquitoes. All samples on dry ice were transferred to
      laboratory and the presence of the virus was detected using reverse transcriptase
      PCR. RESULTS: A total of 1,245 mosquito larvae were collected during larval
      survey and 2,019 adult mosquitoes were collected using aspirator. From these
      collections, 640 mosquito pools were tested for the presence of CHIKV by RT-PCR
      but none found positive. Ae. albopictus was the most abundant mosquito collected,
      followed by Culex sp., Armigeres sp. and Anopheles sp. A total of 2, 814
      artificial containers were inspected during the study. INTERPRETATION &
      CONCLUSIONS: Since none of the mosquito samples was found to be positive for
      chikungunya virus, the vector(s) of chikungunya virus in these localities could
      not be identified.

PMID- 21727670
TI  - Virulence potential of Group A streptococci isolated from throat cultures of
      children from north India.
AB  - BACKGROUND & OBJECTIVES: Rheumatic fever (RF)/rheumatic heart disease (RHD)
      caused by Group A streptococcus (GAS) are more prevalent in north India as
      compared to the western world, where invasive diseases are common. This could be
      due to variation in the virulence of GAS in different geographic locations.
      Hence, we studied the virulence potential of GAS isolated from the throat of
      children from north India. METHODS: Fifty GAS isolated consecutively, from
      children with mild pharyngitis (20), severe pharyngitis (24) and asymptomatic
      pharyngeal carriers (6), were characterized by emm typing and opacity factor
      (OF). Adherence and internalization of GAS in HEp-2 cells and opsonophagocytosis
      in convalescent serum samples were studied. RESULTS: Twenty emm types, six
      sequence types, and one non-typeable GAS were circulating in the community. emm
      type 74, 11, 68, StI129 and NS292 were most prevalent. Twenty seven (54%) GAS
      isolates were OF negative. Sixty five per cent of the most prevalent emm types
      were OF negative indicating their rheumatogenic potential. Adhesion of GAS ranged
      from 0.1 to 100 per cent. Forty eight per cent of GAS were highly adherent.
      Invasion of GAS in HEp-2 cells ranged between 0 to 30 per cent. Only 20 per cent
      isolates exhibited highest invasion. GAS were opsonophagocytosed with highly
      divergent efficiency ranging from 0 to 91.7 per cent. Nineteen GAS were not
      opsonophagocytosed and 15 multiplied during the assay. Isolates of the same emm
      type also varied in their virulence potential. INTERPRETATION & CONCLUSIONS: GAS
      isolates from the throat of children from north India belonged to several emm
      types, majority were OF negative, excellent adherents but poor invaders. This
      explains why throat infections in these children tend to lead to ARF/RHD rather
      than invasive diseases. A few isolates exhibiting high invasion efficiency
      indicate that GAS throat cultures can also lead to invasive diseases.

PMID- 21727671
TI  - Emergence of tigecycline & colistin resistant Acinetobacter baumanii in patients
      with complicated urinary tract infections in north India.

PMID- 21727672
TI  - Economic growth & health of poor children in India.

PMID- 21727673
TI  - Evidence-based preventive interventions for targeting under-nutrition in the
      Indian context.

PMID- 21727674
TI  - Understanding the current status and exploring the potential for distance
      education in public health in India.
AB  - Continuing education of health care providers plays an important role in
      producing a health work force that is efficient and effective. In India public
      health education has primarily relied on conventional methods of training.
      However, such methods have limitations in equipping the health workforce of a
      vast and varied country like India. This paper analyzes the current status of
      distance education in public health and lists the various courses that are
      presently available in India through the distance education mode. Presently 25
      institutions in India are offering 69 courses in various domains of public health
      through distance education. The providers of these programs comprised both
      government and private educational institutions. This paper also points out the
      role and importance of various stakeholders in the design and delivery of
      distance education programs in public health and raises key areas that need
      attention in the governance of such programs. It urges the use of digital
      technology in the delivery of distance education programs and points out how
      distance education that is designed and delivered using the latest technology
      could address the current gap in training human resources for health in India.

PMID- 21727675
TI  - Risk factors associated with MDR-TB at the onset of therapy among new cases
      registered with the RNTCP in Mumbai, India.
AB  - BACKGROUND: Multidrug - resistant TB (MDR - TB) has emerged as a major threat to
      global TB control efforts in recent years. Facilities for its diagnosis and
      treatment are limited in many high - burden countries, including India. In hyper 
      endemic areas like Mumbai, screening for newly diagnosed cases at a higher risk
      of acquiring MDR - TB is necessary, for initiating appropriate and timely
      treatment, to prevent its further spread. OBJECTIVE: To assess risk factors
      associated with MDR - TB among Category I, new sputum smear-positive cases, at
      the onset of therapy. MATERIALS AND METHODS: The study applied an unmatched case 
      control design for 514 patients (106 cases with MDR - TB strains and 408
      controls with non - MDR - TB strains). The patients were registered with the
      Revised National Tuberculosis Control Program (RNTCP) in four selected wards of
      Mumbai during April 2004 - January 2007. Data were collected through semi -
      structured interviews and drug susceptibility test results. RESULTS: Multivariate
      analysis indicated that infection with the Beijing strain (OR = 3.06; 95% C.I. =
      1.12 - 8.38; P = 0.029) and female gender (OR = 1.68; 95% C.I. = 1.02 - 2.87; P =
      0.042) were significant predictors of MDR-TB at the onset of therapy. CONCLUSION:
      The study provides a starting point to further examine the usefulness of these
      risk factors as screening tools in identifying individuals with MDR-TB, in
      settings where diagnostic and treatment facilities for MDR-TB are limited.

PMID- 21727676
TI  - A study on visual outcomes after cataract surgery with intraocular lens implants
      at the rural health training center, Paithan, Maharashtra.
AB  - A study was conducted to assess the visual outcomes of patients after cataract
      surgery with intraocular lens implants with reference to visual acuity (VA) and
      visual function (VF) and to assess patient satisfaction with surgical outcome.
      The retrospective study was carried out using operation theatre records at the
      Rural Health Training Centre (RHTC), Paithan, during 2007. Out of 819 cataract
      surgery patients operated in 2007 a total of 50 were selected randomly. Door-to
      door visits were paid by investigator and multipurpose worker to previously
      operated patients for VA examination and to fill predesigned questionnaire.
      Statistical analysis was done by using SPSS 17.0 Version; 50% patients had VA in
      fair vision range of <6/18-6/60 and 52% showed the VF in the range of 76-100. Of
      the 32 satisfied patients, majority were in the age group 70-79 years. The
      patients with good visual outcomes achieved after surgery would act as pamphlets
      for the community.

PMID- 21727677
TI  - Geriatric health: need to make it an essential element of primary health care.
AB  - Within the next few decades, we will see an extraordinary increase in the number
      of older people worldwide. The public health benefit of preventive medicine in
      old age comes from the compression of the time spent in dependency to a minimum.
      A community-based, cross-sectional study was conducted to assess the morbidity
      profile of the geriatric population in a rural area of Maharashtra. A total of
      214 subjects, of age 60 years and above, were examined. Data were collected by
      structured interviews and clinical and laboratory examinations. Out of the total
      of 214 subjects, 190 were suffering from some or the other diseases and the major
      morbidities were visual (56%), musculoskeletal (38.3%), respiratory (32.7%), and
      hypertension (28%). Anemia was present in 62.6%, 5.61% had Diabetes Mellitus and
      22.5% were found to be overweight. The average morbidity load was 2.61. The
      rising morbidities clearly showed that a regular, complete health checkup of the
      elderly should be embedded in the essential elements of the Primary Health Care.
      This would reduce the morbidity, improve the quality of life, and facilitate
      'Active Aging'.

PMID- 21727678
TI  - Performance of audio-assisted confidential voting interview for assessment of
      sexual behavior among young adults in Chandigarh Union Territory.
AB  - A cross-sectional study was conducted in Chandigarh Union Territory to evaluate
      the performance of an audio-assisted confidential voting interview (AVI), for
      assessing the sexual behavior among young adults aged 20 - 34 years. Using
      systematic random sampling 625 males and 630 females were interviewed
      alternately, either by AVI or by face-to-face interview (FFI). More men revealed
      having sex with men in AVI (2.6%) than FFI (0.6%) (P 0.06). Women reported having
      sex with non-regular partners more often in AVI (4.8%) compared to FFI (0.3%) (P
      < 0.001). AVI performed better than FFI for eliciting sensitive sexual behaviors.

PMID- 21727679
TI  - Glucose indices, frank and undetected diabetes in relation to hypertension and
      anthropometry in a South Indian rural population.
AB  - Diabetes has emerged as one of the world's biggest health problems and its
      prevalence is increasing at an alarming rate. This study was conducted to find
      out the magnitude of frank and undetected diabetes mellitus, including impaired
      glucose tolerance (IGT) among persons in rural Karnataka, and its relationship
      with associated risk factors like hypertension and anthropometry. This was a
      population-based, cross-sectional study on 1370 participants in the field
      practice area of KBN Medical College, conducted from April 2009 to March, 2010.
      Diabetes mellitus was noted among 19.78% of the participants, with an additional
      12.04% with impaired glucose tolerance. Hypertension observed among participants
      with diabetes and impaired glucose tolerance was 65.13 and 53.94%, respectively.
      Effective primary prevention strategies have to be intensified among high-risk
      population groups, to promote awareness through behavior change communication.

PMID- 21727680
TI  - Prevalence and health-seeking behavior of reproductive tract infection/sexually
      transmitted infections symptomatics: a cross-sectional study of a rural community
      in the Hooghly district of West Bengal.
AB  - A community-based, descriptive, cross-sectional study was conducted in
      Purushottampur village of the Singur block, Hooghly, using a pre-tested, semi
      structured questionnaire, to find out the prevalence of RTI / STI symptomatics
      among the general population aged 15 to 49 years, and to assess their profiles
      and health-seeking behaviors. Prevalence of (Reproductive tract infection) RTI /
      STI (Sexually transmitted infections) symptoms in the last 12 months was found to
      be 13.9 and 13.6% among males and females, respectively. The most common symptom
      was dysuria and vaginal discharge among males and females, respectively. Almost
      half of the STI symptomatics (52% male, 50% female) did nothing for their
      symptoms. Better health-seeking behavior was observed among females. About 9.4%
      of the males and 47% of the females sought advice from the clinic / hospital /
      health workers. Strengthening of activities of the existing national program
      among the general population is needed to build a positive health-seeking
      behavior that will ensure success of the syndromic management of RTI / STI.

PMID- 21727681
TI  - Prevalence of substance use among male adolescents in an urban slum area of
      Karimnagar district, Andhra Pradesh.
AB  - In recent years substance use has increased greatly throughout the world.
      Adolescence is the critical period when the first initiation of substance use
      takes place. Interventions at the adolescent age are effective to bring about
      lifestyle modifications. A community-based, cross-sectional study was carried out
      among 260 randomly selected adolescents in an urban slum area, with the objective
      of studying the prevalence and determinants of substance use among adolescents.
      The adolescent age group was selected as defined by the World Health Organization
      (WHO) (10 - 19 years). The overall prevalence of substance use was 32.7%. About
      31% initiated substance use at 13 - 15 years of age, and the reason was peer
      pressure in 52.9%. Education of the study subject, education of parents, and
      substance use by parents and by peers were significantly associated with
      substance use. Children and parents should be educated to prevent substance use.
      There was a need to change the social environment.

PMID- 21727682
TI  - Structural and qualitative evaluation of microscopy and directly observed
      treatment centers under revised national tuberculosis control programme in Nanded
      city of Maharashtra.
AB  - Structural and qualitative evaluation of Revised National Tuberculosis Control
      Programme (RNTCP) is important to determine actual status of the programme in the
      field settings and to uncover the concealed gaps. The present cross-sectional
      study assessed the infrastructural facilities and quality of services provided
      through microscopy and directly observed treatment (DOT) centers at Nanded city
      of Maharashtra. The investigator made on spot observation on the activities at
      microscopy and DOT centers and assessed the infrastructural facilities using an
      observational checklist. Expert microbiologist cross checked the microscopy
      report done by the laboratory technicians. It revealed that retrieval mechanism
      was not functioning in more than half of the DOT centers. Only 5 DOT providers
      were trained in RNTCP. Stock of sputum containers, methylene blue, and carbol
      fuchsin was found to be inadequate at some microscopy centers. Half of the
      laboratory technicians reported high false positive result in spite of being
      trained. Improvement of infrastructural and logistic support along with the
      refreshing training for the workers are needed for effective implementation of
      RNTCP.

PMID- 21727683
TI  - Sanitation: the hygienic means of promoting health.

PMID- 21727684
TI  - A mercury free health care organization: a must.

PMID- 21727685
TI  - Validity of results obtained from thirty clusters on "prevalence of iodine
      deficiency disorders" drawn from a large state in India.

PMID- 21727686
TI  - Community medicine departments and public health education in India at
      crossroads!

PMID- 21727687
TI  - What is new in autoimmune vesicobullous disorders?

PMID- 21727688
TI  - Skin in aviation and space environment.
AB  - The aerospace environment is a dynamic interaction between man, machine and the
      environment. Skin diseases are not particularly significant aeromedically, yet
      they could permanently affect an aviator's status for continued flying duty. A
      number of dermatological conditions lend themselves to flying restrictions for
      the aviator. Aircrew and ground crew are exposed to a myriad of elements that
      could also adversely impact their flying status. Inflight stresses during flights
      as well as space travel could impact certain behaviors from a dermatological
      standpoint. With the advent of space tourism, dermatological issues would form an
      integral part of medical clearances. With limited literature available on this
      subject, the review article aims to sensitize the readers to the diverse
      interactions of dermatology with the aerospace environment.

PMID- 21727689
TI  - Lichenoid tissue reaction/interface dermatitis: recognition, classification,
      etiology, and clinicopathological overtones.
AB  - Lichenoid tissue reaction or interface dermatitis embrace several clinical
      conditions, the prototype of which is lichen planus and its variants, drug
      induced lichenoid dermatitis, special forms of lichenoid dermatitis, lichenoid
      dermatitis in lupus erythematosus, and miscellaneous disorders showing lichenoid
      dermatitis, the salient clinical and histological features of which are described
      to facilitate their diagnosis. Background of lichenoid reaction pattern has been
      briefly outlined to enlighten those interested in this entity.

PMID- 21727690
TI  - Epidermolysis bullosa: where do we stand?
AB  - Epidermolysis bullosa, a genetically determined skin fragility disorder can
      severely incapacitate the life of the afflicted patient. Although the clinical
      features are multiple and varied, treatment still remains a major challenge.
      There have been major changes in the classification of the disease recently.
      Although there is still a long way to go, good nursing care, and gene therapy
      could possibly significantly alleviate the suffering of the patients in the
      future.

PMID- 21727691
TI  - Pemphigus in India.
AB  - Pemphigus is a chronic epidermal immunobullous disease with potentially fatal
      outcome. The journey of literature on pemphigus in India has come a long way in
      last five decades. Pemphigus in Indian patients has unique genetic, clinical, and
      epidemiological differences from those in the Western countries. Corticosteroids
      remain the mainstay of treatment for pemphigus. Dexamethasone-cyclophosphamide
      pulse therapy has revolutionized the management of pemphigus in India and abroad
      for nearly 3 decades now. Corticosteroid-based treatment, along with adjuvants,
      has significantly brought down the high mortality rates that had been observed in
      precorticosteroid era. Present day research is largely based on elucidating the
      pathogenesis beyond the antidesmoglein antibodies, and newer diagnostic and
      treatment approaches. In this article, we review various aspects of literature on
      pemphigus in India, on Indians abroad, or literature from other countries that
      are considered relevant to the topic.

PMID- 21727692
TI  - Bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is a relatively common autoimmune vesicobullous disease
      encountered in India. It is a subepidermal bullous disorder most commonly seen in
      the elderly and manifests as tense blisters on urticarial base, predominantly
      over flexures, and is associated with pruritus. The diagnosis can be confirmed by
      histology, direct and indirect immunofluorescence. Several new diagnostic
      techniques have also been developed. Treatment of BP is based on the extent and
      rate of progression of the disease. Several topical and systemic anti
      inflammatory and immunosuppressive agents have been used with variable results.

PMID- 21727693
TI  - Evidence-based treatments for pemphigus vulgaris, pemphigus foliaceus, and
      bullous pemphigoid: a systematic review.
AB  - BACKGROUND: Pemphigus, bullous pemphigoid, and epidermolysis bullosa acquisita
      are autoimmune diseases of skin associated with considerable morbidity and
      sometimes mortality. There is no cure for these diseases. AIMS: To summarize
      evidence-based treatments for these diseases by performing a systematic review.
      METHODS: The research protocol included the following steps: identification of
      databases to be searched, defining search strategy, searching the databases for
      references, first-stage screening of the abstracts, second-stage screening of
      full texts of articles identified after the first-stage screening, data
      extraction from the identified articles after second-stage screening, quality
      appraisal of the studies using the Delphi list, and summarizing the findings.
      RESULTS: No randomized controlled trials of interventions in pemphigus vegetans,
      pemphigus erythematosus, and epidermolysis bullosa acquisita could be found.
      After the second-stage screening, 12 randomized controlled trials were analyzed,
      which included patients with pemphigus vulgaris or pemphigus vulgaris and
      pemphigus foliaceus, and 7 which included patients with bullous pemphigoid.
      CONCLUSIONS: Number of high-quality randomized controlled trials conducted on
      pemphigus and bullous pemphigoid is small. Oral corticosteroid along with a
      steroid-sparing agent appears to be the most effective treatment for pemphigus.
      Azathioprine may be most effective as a steroid-sparing agent. Topical
      corticosteroid therapy (as studied) is effective for bullous pemphigoid and
      appears to be superior to oral corticosteroid for extensive disease. Some
      suggestions about future research are made.

PMID- 21727694
TI  - Dermatoses in the first 72 h of life: a clinical and statistical survey.
AB  - BACKGROUND: The neonatal period is generally regarded as the first 28 days of
      extrauterine life. Skin disorders are commonly seen in the neonatal period, most
      of which are transient and limited to the first days or weeks of life. In spite
      of being so frequent, these transient conditions usually escape dermatologist's
      observations, and consequently few have been studied. AIMS: The study was
      designed to identify the dermatoses in the first 72 h of life; to report the
      relationship among the most common dermatoses with the newborn's features; and to
      verify how often dermatoses are reported by the neonatologist. METHODS: The
      authors carried out a cross-sectional study on newborn's dermatoses in a
      brazilian public hospital, including 203 healthy neonates, until 72 h of age,
      with skin disorders. RESULTS: Out of 34 different skin diagnosed conditions,
      hypertrichosis lanuginosa, Mongolian spot, sebaceous hyperplasia, epidermal
      hyperpigmentation, erythema toxicum, and salmon patch were the most frequent
      ones. The dermatoses with statistical significance were: Mongolian spot and
      epidermal hyperpigmentation with the non-white newborns; erythema toxicum and
      cutis marmorata with the white newborns; salmon patch with the female sex;
      physiologic desquamation with the cesarean section; acrocyanosis with the first
      pregnancy birth and Bohn's nodules with the vaginal delivery. CONCLUSIONS: Thirty
      four different types of dermatological alterations were identified in the healthy
      newborn within 3 days of life at the Maternity School of the Federal University
      of Rio de Janeiro. Underreporting of dermatoses with serious medical significance
      shows the importance of a dermatologist in the neonatal unit of a hospital.

PMID- 21727695
TI  - Chronic urticaria in patients with autoimmune thyroiditis: significance of
      severity of thyroid gland inflammation.
AB  - BACKGROUND: There is a clear association between autoimmune thyroiditis (AT) and
      chronic urticaria/angioedema (CUA). However, not all patients with AT demonstrate
      urticaria. AIMS: The aim of the study was to investigate in which patients with
      AT did CUA become a problem. A sensitive inflammation marker, neopterine (NP) was
      used to confirm whether the severity of inflammation in the thyroid gland was
      responsible for urticaria or not. METHODS: Neopterine levels were assessed in
      patients with AT with urticaria and without urticaria. Furthermore, levels were
      compared in relation to pre and post levothyroxine treatment. Twenty-seven
      patients with urticaria (Group 1) and 28 patients without urticaria (Group 2)
      were enrolled in the study. A course of levothyroxine treatment was given to all
      patients, and urine neopterine levels before and after the trial were obtained.
      RESULTS: All patients completed the trial. Mean age in Group 1 and Group 2 was
      similar (35.70 +/- 10.86 years and 38.36 +/- 10.38 years, respectively)
      (P=0.358). Pre-treatment urine neopterine levels were significantly higher in
      Group 1 (P=0.012). Post-treatment levels decreased in each group, as expected.
      However, the decrease in the neopterine level was insignificant in the patients
      of Group 2 (P=0.282). In Group 1, a significant decrease in post-treatment
      neopterine levels (P=0.015) was associated with the remission of urticaria.
      CONCLUSION: In patients with CUA and AT, pre-treatment elevated levels of NP, and
      its decrease with levothyroxine treatment along with symptomatic relief in
      urticaria, may be evidence of the relationship between the degree of inflammation
      in thyroid and presence of urticaria.

PMID- 21727696
TI  - Spectrum of seborrheic keratoses in South Indians: a clinical and dermoscopic
      study.
AB  - BACKGROUND: Even though seborrheic keratoses (SK) have been well characterized
      clinically and histopathologically, data regarding clinical and dermoscopic
      correlation of different types of SK are inadequate. AIMS: We carried out a study
      to establish any correlation between the clinical and dermoscopic appearance of
      SK and its variants. METHODS: This was a descriptive study conducted in the
      Department of Dermatology, a tertiary care institute, from August 2008 to June
      2010. Patients with SK were evaluated with respect to age, sex, age of onset,
      duration, site of lesions, number of lesions, and morphology. Dermoscopy was
      performed in all cases. RESULTS: A total of 250 cases of SK were recruited. A
      male-to-female ratio was 1:1.04. The most common age group affected by SK was 60
      years and above (40%). The most common clinical variant was common seborrheic
      keratosis (CSK) (60%). Comedo-like openings (CL) (80%), fissures and ridges (FR)
      (52%), and sharp demarcation (SD) (83%) were consistent finding on dermoscopy in
      CSK. Dermatosis papulosa nigra (DPN) and pedunculated seborrheic keratoses (PSK)
      had characteristic CL and FR in both of them. Fingerprint (FP) (55%) and network
      like (NL) (88%) structures were commonly seen in flat SK. Stucco keratoses
      demonstrated SD (100%) and NL structures (100%). CONCLUSIONS: The most common
      clinical variant of SK was CSK, followed by DPN, PSK, Flat SK, and stucco
      keratoses. Dermoscopic findings were consistent with those described in the
      literature.

PMID- 21727697
TI  - Clinical profile and impact on quality of life: seven years experience with
      patients of alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is the most common cause of localized, non
      scarring alopecia. Stress and other psychological factors have been implicated in
      the causation of the disease, and it is also found to alter the course of the
      disease process. Unfortunately no one has studied the impact of AA on the quality
      of life, which includes the social life of the patients. AIM: To study the
      clinical profile and impact of alopecia areata on the quality of life, including
      the social life of adult patients with severe forms of the disease. METHODS: The
      present study determined the clinical pattern of AA and its impact on the quality
      of life (QOL) in all the patients with severe forms of alopecia areata attending
      the Dermatology Outpatient Department. RESULTS: The male : female ratio was 1.86
      : 1. Most (58.03%) of the patients were between 21 and 40 years of age. Almost
      40% of the patients had associated systemic disease or other dermatological
      disorders. A family history of AA was found in 593 (20.02%) of the patients. Nail
      changes were observed in 297 (10%) of the patients. There were significant
      differences between the mean Dermatology Life Quality Index (DLQI) score in cases
      with severe forms of AA and controls ( P < 0.001). CONCLUSIONS: Severe forms of
      alopecia areata had a major impact on the psychosocial well-being of the
      patients. These individuals had to be treated early, and they required more than
      just prescription drugs. Educational and psychological support in addition to
      medical therapy for AA could improve their long-term physical outcomes.

PMID- 21727698
TI  - Isolated distal cutaneous thrombosis: an unusual presentation and an interesting
      etiology.
AB  - A middle-aged hypertensive male, with a fatty liver and chronic alcohol intake,
      relocated to a high altitude of 2100 m above sea level; in the first winter
      season, he developed bluish skin lesions over the tip of the nose, margins of
      both ear lobes, both knees, and subungual location. Systemic examination was
      unremarkable. Skin biopsy showed thrombi in dermal vessels without any evidence
      of vasculitis; immunofluorescence was negative. Investigations revealed mild
      elevation in plasma homocysteine levels, weakly positive antinuclear antibodies
      and elevated antiphospholipid antibodies, methylene tetrahydrofolate reductase
      C677T heterozygosity, and protein S deficiency. The patient received prednisolone
      for 2 weeks, aspirin and pentoxyphylline for 3 months, and continues to be on
      folic acid and vitamin B6. After 3 months, antiphospholipid antibodies and
      antinuclear antibody levels were normal. Isolated distal cutaneous thrombosis is
      an uncommon entity and precipitation by extreme cold in a hypertensive male with
      three thrombophilic states - one transient, one hereditary, and one acquired - is
      fascinating.

PMID- 21727699
TI  - Generalized eruptive histiocytosis mimicking leprosy.
AB  - Generalized eruptive histiocytosis (GEH) is a rare cutaneous histiocytosis that
      mainly affects adults and presents with multiple symmetric papules on face,
      trunk, and proximal extremities. GEH is included in type IIa (histiocytes
      involving cells of dermal dendrocyte lineage) of histiocytic disorders. Clinical
      and pathological correlations are required for differentiating GEH from other
      histiocytic disorders and from lepromatous leprosy which clinically mimic GEH and
      is prevalent in India. We report a case of a middle-aged woman who presented with
      generalized asymptomatic papules and nodules and was treated for leprosy but was
      finally diagnosed to have GEH after clinical, histopathological, and
      immunohistochemical correlation. Furthermore, the newer lesions also showed
      features of progressive nodular histiocytosis.

PMID- 21727700
TI  - Ectodermal dysplasia-skin fragility syndrome.
AB  - Ectodermal dysplasia-skin fragility (EDSF) syndrome is a rare and first described
      inherited disorder of desmosomes. It occurs due to loss-of-function mutations in
      PKP1 gene resulting in poorly formed desmosomes and loss of desmosomal and
      epidermal integrity. We report a case of a 2-year-old Indian male child who
      presented with palmoplantar hyperkeratosis with fissuring, short, sparse, and
      easily pluckable scalp hair, nail dystrophy, and multiple erosions over the skin.
      Skin biopsy showed epidermal hyperplasia with widening of intercellular spaces.
      His developmental milestones were delayed but intelligence was normal.
      Echocardiography, X-ray chest, and electrocardiogram were normal. Very few cases
      of this syndrome have been reported in the literature. We consider this as the
      first case report from India.

PMID- 21727701
TI  - Spontaneous regression of a congenital melanocytic nevus.
AB  - Congenital melanocytic nevus (CMN) may rarely regress which may also be
      associated with a halo or vitiligo. We describe a 10-year-old girl who presented
      with CMN on the left leg since birth, which recently started to regress
      spontaneously with associated depigmentation in the lesion and at a distant site.
      Dermoscopy performed at different sites of the regressing lesion demonstrated
      loss of epidermal pigments first followed by loss of dermal pigments.
      Histopathology and Masson-Fontana stain demonstrated lymphocytic infiltration and
      loss of pigment production in the regressing area. Immunohistochemistry staining
      (S100 and HMB-45), however, showed that nevus cells were present in the
      regressing areas.

PMID- 21727702
TI  - Epidemiological trends in contact dermatitis to hair dye: Comparing para
      phenylenediamine positivity after a decade long interval.

PMID- 21727703
TI  - Retrospective study of spectrum of cutaneous lymphoma presenting to dermatology.

PMID- 21727704
TI  - Perforating lichen planus.

PMID- 21727705
TI  - Gigantic cutaneous rhinosporidiosis with giant cells bloated with sporangia.

PMID- 21727706
TI  - Multiple eruptive milia over both external ears.

PMID- 21727707
TI  - Co-existent acquired perforating collagenosis and lepromatous leprosy with
      erythema nodosum leprosum: response to treatment.

PMID- 21727708
TI  - Extralesional vitiligo over knee following halo nevus with poliosis on the scalp.

PMID- 21727709
TI  - The oral and skin pathergy test.

PMID- 21727710
TI  - Perifollicular nodule on the face of a young man.

PMID- 21727711
TI  - Ethionamide-induced pellagroid dermatitis resembling lichen simplex chronicus: a
      report of two cases.
AB  - Pellagra is a niacin deficiency disorder characterized clinically by diarrhea,
      dermatitis, and dementia. However, few drugs also cause pellagroid dermatitis.
      Recently, we encountered two cases of pellagroid dermatitis; both were on second
      line of antituberculosis drugs. Case 1 was of multidrug-resistant pulmonary
      tuberculosis. Patient was on ethionamide since one year before developing
      pellagroid dermatitis. Case 2 was of central nervous system tuberculoma and was
      on second line of antitubercular drugs. This patient was on ethionamide and
      isoniazid (INH) since six months before developing pellagroid dermatitis. This
      patient had previously taken first line of antituberculous therapy, inclusive of
      INH, for 1 year without any dermatitis. The skin lesions in both patients were
      symmetric hyperpigmented thickened plaques with prominent skin markings
      resembling lichen simplex chronicus. Nicotinamide 300 mg in three divided doses
      healed the lesions completely within 4 weeks and 3 weeks in first and second
      patient, respectively.

PMID- 21727712
TI  - Pemphigus and pregnancy: a 23-year experience.
AB  - BACKGROUND: Studies on the interaction of pemphigus and pregnancy are limited to
      case reports and small case series. Pregnancy is not rare in Iranian pemphigus
      patients due to lower age at onset of the disease. AIM: We sought to investigate
      the outcome of pregnancy and the course of pemphigus in pemphigus patients in a
      retrospective study. METHODS: The files of 779 pemphigus women younger than 50
      presenting to our center from 1984 till 2006 were examined for any mention of
      pregnancy. Data related to outcome of pregnancy and the course of the disease
      were collected. RESULTS: Sixty-six patients with a history of pregnancy were
      identified. Forty-eight known pemphigus patients experienced one or more
      pregnancies during their disease (total pregnancy number: 52). The course of
      pemphigus was as follows in this group: 28 cases (54%) of exacerbation, 15 cases
      (31%) with no alteration, and 9 cases (17%) showing improvement. The rate of
      abortion was 9.6% (5 cases). In 18 cases, the disease had started during
      pregnancy, 2 of them (11%) ended in an abortion. Overall, postpartum flare was
      seen in 33 cases (47.1%). CONCLUSION: Pemphigus may be exacerbated during or
      after pregnancy, but often to a mild degree. Although the rate of stillbirth was
      not as high as previously reported, the rate of abortion was considerable.
      Pregnancy may have an uneventful course, especially in patients in clinical
      remission; nevertheless, careful monitoring of the high risk mother and fetus is
      mandatory.

PMID- 21727713
TI  - Tufted hair folliculitis with linear arrangement.

PMID- 21727714
TI  - Frequency of birthmarks and transient skin lesions in newborns according to
      maternal factors (diseases, drugs, dietary supplements, and tobacco).

PMID- 21727715
TI  - Human leukocyte antigen in patients with psoriasis.

PMID- 21727716
TI  - Sporotrichoid nocardiosis with cutaneous dissemination.
AB  - Dissemination of primary cutaneous nocardiosis is a rare event. A 37-year-old man
      working as farmer presented with multiple painful suppurative nodular and
      ulcerative skin lesions over left lower extremities, in a linear pattern, with
      duration of five months and single painful nodule over right elbow since last
      three months. We found the presence of beaded filamentous bacteria in Gram stain
      smear and partial acid fast stain, from the smear taken from pus. Patient
      responded well to cotrimoxazole therapy. Hence, we confirm our diagnosis of
      sporotrichoid pattern of cutaneous nocardiosis with dissemination to other
      cutaneous area.

PMID- 21727717
TI  - Systemic (allergic) contact dermatitis to diclofenac.

PMID- 21727718
TI  - Laugier-Hunziker syndrome.

PMID- 21727719
TI  - "Paradoxical" adverse effects caused by anti-tumor necrosis factor-alpha
      biological drugs: appearance of psoriasis in a patient treated with infliximab
      for rheumatoid arthritis.

PMID- 21727720
TI  - Treatment of recalcitrant granulomatous rosacea with ALA-PDT: report of a case.

PMID- 21727721
TI  - Idiopathic sporadic tumoral calcinosis in an Indian girl.

PMID- 21727722
TI  - Disseminated asymptomatic yellowish papules on the face, trunk and limbs in a 3
      year-old boy.

PMID- 21727723
TI  - Cutaneous metastasis of the small cell lung cancer.

PMID- 21727724
TI  - Vancomycin-induced linear IgA bullous dermatosis mimicking toxic epidermal
      necrolysis.

PMID- 21727725
TI  - Laparoscopic versus open appendectomy.

PMID- 21727726
TI  - How can we reduce the burden of Hepatitis C?

PMID- 21727727
TI  - Short bowel syndrome: a review of management options.
AB  - Extensive resection of the intestinal tract frequently results in inadequate
      digestion and/or absorption of nutrients, a condition known as short bowel
      syndrome (SBS). This challenging condition demands a dedicated multidisciplinary
      team effort to overcome the morbidity and mortality in these patients. With
      advances in critical care management, more and more patients survive the
      immediate morbidity of massive intestinal resection to present with SBS. Several
      therapies, including parenteral nutrition (PN), bowel rehabilitation and surgical
      procedures to reconstruct bowel have been used in these patients. Novel dietary
      approaches, pharmacotherapy and timely surgical interventions have all added to
      the improved outcome in these patients. However, these treatments only partially
      correct the underlying problem of reduced bowel function and have limited success
      resulting in 30% to 50% mortality rates. However, increasing experience and
      encouraging results of intestinal transplantation has added a new dimension to
      the management of SBS. Literature available on SBS is exhaustive but
      inconclusive. We conducted a review of scientific literature and electronic media
      with search terms 'short bowel syndrome, advances in SBS and SBS' and attempted
      to give a comprehensive account on this topic with emphasis on the recent
      advances in its management.

PMID- 21727728
TI  - Laparoscopic versus open appendectomy: a comparison of primary outcome measures.
AB  - BACKGROUND/AIM: The aim of the study was to compare laparoscopic and open
      appendectomy (OA) in terms of primary outcome measures. STUDY DESIGN: A
      randomized controlled trial. Place and duration of the study: Khyber Teaching
      Hospital, Peshawar, Pakistan, February 2008 to December 2009. PATIENTS AND
      METHODS: A total of 160 patients were divided into two groups, A and B. Group A
      patients were subjected to laparoscopic appendectomy (LA), whereas Group B
      patients were subjected to OA. Data regarding age, gender, and primary outcome
      measures, such as hospital stay, operative duration, and postoperative
      complication, were recorded and analyzed. Percentages were calculated for
      categorical data, whereas numerical data were represented as mean +/- SD. Chi
      square test and t test were used to compare categorical and numerical variables,
      respectively. Probability <= 0.05 (P <= 0.05) was considered significant.
      RESULTS: After randomization, 72 patients in group A and 75 patients in group B
      were analyzed. The mean age of patients in groups A and B was 23.09 +/- 8.51 and
      23.12 +/- 10.42 years, respectively, (P = 0.981). The mean hospital stay was 1.52
      +/- 0.76 days in group A and 1.70 +/- 1.06 days in group B (P = 0.294). The mean
      operative duration in group A and B were 47.54 +/- 12.82 min and 31.36 +/- 11.43
      min, respectively (P < 0.001). Pain (overall level) was significantly less in
      group A compared with group B (P = 0.004). The two groups were comparable in
      terms of other postoperative complications, such as hematoma (P = 0.87),
      paralytic ileus (P = 0.086), urinary retention (P = 0.504), and wound infection
      (P = 0.134). CONCLUSION: LA is an equivalent procedure and not superior to OA in
      terms of primary outcome measures.

PMID- 21727729
TI  - Diversity of genotype and mode of spread of Hepatitis C virus in Northern India.
AB  - BACKGROUND/AIM: Hepatitis C is caused by hepatitis C virus (HCV), which is
      classified into 6 genotypes. It leads to chronic hepatitis in 80% of the cases.
      Genotype of the virus helps in predicting response to antiviral therapy and also
      the duration of treatment. Therefore, it is important to know the prevalence of
      each genotype. Knowledge regarding the route of entry of HCV in the blood is also
      necessary to formulate a strategy to prevent its spread. PATIENTS AND METHODS:
      One hundred and two newly diagnosed patients with chronic hepatitis C, having
      anti-HCV antibody-positive were included in the study. Their HCV RNA viral load
      and genotype were determined by Reverse Transcriptase PCR assay on Roche Cobas
      Ampliprep analyzer. RESULTS: Genotype 3 was commonly detected in 58.8% patients
      followed by genotype 1 in 20.6%. Twelve patients had genotype 4 (11.8%) and 9 had
      mixed infection with genotypes 3 and 4. Among these patients, 43.1% of patients
      had a history of multiple injection exposure. Blood transfusion received by 6.9%
      and 2.9% had donated blood. Only 1 patient had a history of drug abuse.
      CONCLUSION: The distribution of genotypes varies in different regions and
      therefore its knowledge is important, as it determines the response of the
      patient to the treatment. The use of autodisabled syringes, their proper
      disposal, following biomedical waste management guidelines, and organizing
      continued medical education and workshops will help in preventing the spread of
      HCV infection.

PMID- 21727730
TI  - Insulin resistance, steatosis, and fibrosis in Egyptian patients with chronic
      Hepatitis C virus infection.
AB  - BACKGROUND/AIM: Both nonalcoholic fatty liver disease (NAFLD) and chronic
      hepatitis C virus (HCV) infection are common in Egypt, and their coexistence is
      expected. There is controversy regarding the influence of NAFLD on chronic HCV
      disease progression. This study evaluates the effect of NAFLD on the severity of
      chronic hepatitis C (CHC) (necroinflammation and fibrosis) and assesses the
      relative contribution of insulin resistance syndrome to the occurrence of NAFLD
      in patients with chronic HCV infection. PATIENTS AND METHODS: Untreated
      consecutive adults with chronic HCV infection admitted for liver biopsy were
      included in this study. Before liver biopsy, a questionnaire for risk factors was
      completed prospectively, and a blood sample was obtained for laboratory analysis.
      RESULTS: Our study included 92 male patients. Their mean +/- SD age and aspartate
      aminotransferase (AST) level were 42 +/- 7.7 years (range 20-56) and 68 +/- 41.7
      U/L (range 16-214), respectively. The mean insulin level and insulin resistance
      index were 15.6 +/- 18.3 mIU/mL (range 5.1-137.4) and 5.9 +/- 15.2 (range 0.9
      136.2), respectively. Fifty four percent of patients had steatosis and 65% had
      fibrosis. In multivariate analyses, steatosis was associated with insulin
      resistance and fibrosis was associated with high AST level, age >=40 years, and
      steatosis. CONCLUSIONS: Steatosis is a histopathologic feature in >50% of
      patients with chronic HCV infection. Insulin resistance has an important role in
      the pathogenesis of steatosis, which represents a significant determinant of
      fibrosis together with high serum AST level and older age.

PMID- 21727731
TI  - Pattern of liver function tests in morbidly obese Saudi patients undergoing
      bariatric surgery.
AB  - BACKGROUND/AIM: Morbidly obese patients have a high prevalence of fatty liver
      disease and its serious complications, and high prevalence of abnormal liver
      function tests (LFT). The LFT can give a clue to the liver damage and correlate
      with activity. We aim to study the pattern of LFT in morbidly obese Saudi
      patients undergoing bariatric surgery in Eastern region. PATIENTS AND METHODS:
      Medical records of patients undergoing bariatric surgery were reviewed.
      Demographic data, comorbid conditions, and medications taken were recorded.
      Intraoperative liver appearance was noted. Patients with alcohol intake or
      without LFT were excluded. RESULTS: Out of 113 patients, 15 patients were
      excluded, and of the remaining 98 patients analyzed, 58.2% were females. Mean age
      was 33.1 +/- 8.87 years. Mean body mass index (BMI) was 53.7 +/- 1.27 kg/m 2 .
      Abnormal LFT (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST)
      alkaline phosphatase (ALK), and Gamma glutamyl transpeptidase (GTT) were observed
      in 17.3%, with 1.5 to 2 times the upper limit of normal. ALT was most elevated in
      12.2%. Abdominal ultrasonography was done in 67 (68.4%) patients, of whom 51
      (76%) had fatty liver. Comorbid conditions including diabetes mellitus,
      hypertension, hyperlipidemia, bronchial asthma, and obstructive sleep apnea were
      observed in 51 (51.50%) patients, eight of them (16.3%) had abnormal LFT. No
      intraoperative changes of cirrhosis were observed. CONCLUSION: The prevalence of
      abnormal LFT is low in morbidly obese patients from the eastern region of Saudi
      Arabia. A prospective study with a larger sample and liver biopsy, is needed to
      clarify the findings.

PMID- 21727732
TI  - Prevalence of alpha-1-antitrypsin gene mutations in Saudi Arabia.
AB  - BACKGROUND/AIM: alpha-1 antitrypsin (AAT) deficiency results from mutations of
      the protease inhibitor (PI). The AAT gene is mapped on chromosome 14 and has been
      associated with chronic liver disease and chronic obstructive pulmonary disease
      (COPD). OBJECTIVE: To determine the frequency of AAT mutations on S and Z carrier
      alleles in healthy Saudi individuals from Qassim Province in Saudi Arabia.
      PATIENTS AND METHODS: A total of 158 healthy, unrelated participants from Qassim
      Province were recruited. They were genotyped for the two AAT-deficiency alleles,
      PIFNx01S and PIFNx01Z, using polymerase chain reaction, with primers designed
      throughout to mediate site-directed mutagenesis. RESULTS: Of the 158 subjects,
      11.39% were carriers for the S mutation (i.e., had the MS genotype), whereas
      2.53% were carriers for the Z mutation (i.e., had the MZ genotype). The SZ
      genotype was present in 3.8% of subjects, while the homozygous genotype SS was
      present in 1.9% of subjects. No subjects showed the ZZ mutant genotype.
      Accordingly, frequency of the mutant S and Z alleles of AAT gene was 9.49% and
      3.19%, respectively. CONCLUSION: The results obtained showed a high prevalence of
      the AAT deficiency allele in the Saudi population. This probably warrants
      adoption of a screening program for at-risk individuals, so that they might
      initiate adequate prophylactic measures.

PMID- 21727733
TI  - Antibiotic susceptibility profile of Helicobacter pylori isolated from the
      dyspepsia patients in Tehran, Iran.
AB  - BACKGROUND/AIM: Helicobacter pylori is an important pathogen for gastroduodenal
      diseases. Infection with H. pylori can be limited by regimens of multiple
      antimicrobial agents. However, antibiotic resistance is a leading cause of
      treatment failure. The aim of this study has been to determine the resistance
      patterns of H. pylori strains isolated from gastric biopsies of patients with
      dyspepsia by agar dilution method, in Tehran, Iran. PATIENTS AND METHODS: H.
      pylori isolates from patients with gastrointestinal diseases were evaluated for
      susceptibility testing by agar dilution method. Susceptibility testing was
      performed to commonly used antibiotics including clarithromycin, tetracycline,
      amoxicillin, metronidazole and ciprofloxacin. RESULTS: Among 92 patients with
      dyspepsia, H. pylori strains were isolated from 42 patients. Seventeen (40.5%) of
      the isolates were resistant to metronidazole (MICs >= 8 MUg/l), whereas one
      isolate (2.4%) was resistant to amoxicillin (MICs <= 0. 5 MUg/ml) and
      ciprofloxacin (MICs <= 1MUg/ml). The resistance rates to other antibiotics in H.
      pylori isolates are recorded as follows: clarithromycin 6 (14.3 %), tetracycline
      2 (4.8%). In 5 of 42 resistant cases, combined resistance was found. CONCLUSIONS:
      These data suggest that metronidazole should be used among Iranian patients in
      first-line therapy with caution, and ciprofloxacin in association with
      amoxicillin and a proton pump inhibitor is more recommended.

PMID- 21727734
TI  - Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian
      children.
AB  - BACKGROUND/AIM: Polymorphisms in the promoter of microsomal triglyceride transfer
      protein (MTP) lead to decreased MTP transcription, less export of triglyceride
      from hepatocytes, and greater intracellular triglyceride accumulation. Therefore,
      functional polymorphisms in MTP may be involved in determining susceptibility to
      nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the
      effect of some genetic influences among a group of obese Egyptian children.
      PATIENTS AND METHODS: A cross-sectional study was conducted on 76 overweight and
      obese children presenting to the Pediatric Endocrinology Unit, Cairo University
      Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric
      measurements were taken for all the patients and they underwent clinical
      examination, ultrasonographic examination of the liver, and liver biopsy when
      appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid
      profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven
      NASH patients and controls were analyzed by polymerase chain reaction (PCR) and
      restriction fragment length polymorphism for the -493 G/T polymorphism in the
      promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting
      sequence of manganese superoxide dismutase (MnSOD). RESULTS: Eight had biopsy
      proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence
      of the MTP G/G genotype (P = 0.002, CI: 2.9-392) compared with the controls. NASH
      patients also had a 100% prevalence of the MnSOD T/T genotype. CONCLUSION:
      Certain genotypes in MTP and MnSOD are significantly more prevalent among obese
      children with NASH and may be responsible for such a phenotype.

PMID- 21727735
TI  - Feasibility and outcome of proximal catheter ileostomy - a pilot study.
AB  - BACKGROUND/AIM: Loop ileostomy has high complication rates and causes much
      patient inconvenience. This study was carried out to evaluate the feasibility and
      outcome of a proximal catheter ileostomy in place of loop ileostomy in patients
      treated by intestinal repair and/or resection-anastomosis. DESIGN: Prospective
      study. SETTING: J. N. Medical College Hospital, Aligarh Muslim University,
      Aligarh, India. PATIENTS AND METHODS: From November 2006 to November 2009, in all
      patients treated surgically by primary repair and/or resection-anastomosis of
      small and/or large bowel, we constructed a catheter ileostomy when a
      defunctioning proximal protective loop ileostomy was considered advisable.
      Catheter ileostomy was constructed in the fashion of catheter jejunostomy, with
      postoperative saline irrigation. RESULTS: Catheter ileostomy was performed in 20
      patients in the 3-year period. The mean age of the subjects was 28.6 years and
      the male: female ratio was 1.86:1. Four patients died of septicemia and multiple
      organ failure unrelated to catheter ileostomy in the immediate postoperative
      period. Catheter ileostomy started functioning within 48 hours of the operation,
      and twice-daily irrigation was found sufficient in 81.25% of the surviving
      patients. Only one patient developed peritubal leak with mild skin excoriation
      that cleared within 5 days. Another patient with Koch's abdomen underwent
      conversion to loop colostomy on re-exploration for postoperative adhesive
      obstruction. There was no instance of intestinal leak. Ileostomy wounds closed
      spontaneously within 7-14 days of catheter removal, and none required formal
      closure. Hospital stay ranged from 12-35 days (mean: 23 days). CONCLUSIONS:
      Catheter ileostomy is effective in protecting intestinal anastomosis/repair;
      there is minimal morbidity and no catheter-related leak/mortality, and we
      recommend the procedure.

PMID- 21727737
TI  - Mediastinal seroma post laparoscopic repair of type IV paraesophageal hernia.
AB  - Laparoscopic repair of paraesophageal hernia is safe and feasible and can provide
      comparable results for patients with type IV paraesophageal hernia. We report a
      rare case of mediastinal seroma in an 80-year-old gentleman who had a giant type
      IV paraesophageal hernia and was eventually admitted to our hospital for elective
      laparoscopic repair and recovered very well after surgery with resolution of the
      atelectatic lungs and air-fluid collection in his chest.

PMID- 21727736
TI  - Laparoscopic cholecystectomy as a day surgery procedure: is it safe?--an egyptian
      experience.
AB  - BACKGROUND/AIM: Major surgery performed as a day surgery procedure is not
      uncommon. The aim of this study is to evaluate the feasibility of day surgery
      procedures in laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: A total of
      210 patients scheduled for elective LC between 2006 and 2008 were included in our
      study. The mean age was 40.63 years (range, 25 - 70 years). The indication for
      surgery was symptomatic cholelithiasis confirmed by ultrasonography without
      clinical or radiological evidence of acute cholecystitis. All patients were
      informed about the same-day discharge policy and received the postoperative
      instruction form on discharge. Preoperative work-up included history taking and
      physical examination in addition to standard laboratory and radiological tests.
      Patients above 35 years of age had an ECG done. All patients were examined in the
      outpatient clinic by a consultant anesthesiologist the night before surgery.
      Operative time, hospital stay, and complications were recorded. Telephonic
      feedback, on the morning after surgery was routinely done as an early follow-up.
      RESULTS: Out of the total number of patients, 140 patients were ASA (I) and 70
      were ASA (II) (40 patients were controlled hypertensives and 30 were controlled
      diabetics). Conversion rate was 1.4%. The mean hospital stay was 6.7 hours
      (range, 6 - 8 hours). The mean operative time was 31.2 minutes (range, 20 - 60
      minutes). None of the patients required an abdominal drain. No morbidities or
      mortalities were reported in this series. CONCLUSION: LC may be done as a day
      surgery procedure with optimal patient satisfaction and without complications.

PMID- 21727738
TI  - Outcome of combination antiviral therapy in chronic hepatitis C virus infection
      during therapy of acute lymphoblastic leukemia.
AB  - Chronic hepatitis C virus (HCV) infection is not uncommon in patients with acute
      leukemia due to frequent blood transfusions. The treatment of HCV in patients
      with acute leukemia can produce profound immune dysfunction with the risk of
      severe cytopenia. We report the case of a young man who was treated with combined
      therapy of peginterferon alpha 2a and ribavirin for HCV while he was on
      maintenance anti-leukemic treatment. The patient required reduction in the dose
      of peginterferon alpha 2a and the addition of filgrastim due to neutropenia.
      Therapy for HCV was continued for 72 weeks and at the end of therapy, the patient
      had undetectable HCV RNA. The patient maintained a sustained viral response two
      years after the end of therapy and developed complete remission of leukemia,
      whereupon his anti-leukemic therapy was also discontinued. We recommend
      conducting further large prospective studies in HCV patients treated for leukemia
      to determine the safety and efficacy of antiviral therapy in this group of
      patients.

PMID- 21727739
TI  - Tuberculous appendicitis.
AB  - Gastrointestinal tuberculosis is quite rare, representing only 3% of all
      extrapulmonary cases. Involvement of the appendix is rare, only occurring in
      about 1% of cases. It is usually secondary to tuberculosis elsewhere in the
      abdomen. A prompt diagnosis depends on a high index of suspicion as clinical
      signs may be nonspecific and microbiological confirmation is difficult.
      Histopathologic examination is often the only way to reach a diagnosis and to
      establish specific antibiotic therapy. In these cases, due to the absence of
      specific symptoms and signs, the diagnosis is delayed until after surgery.

PMID- 21727740
TI  - Unsedated colonoscopy: is it feasible?
AB  - Unsedated colonoscopy has been an evolving subject ever since its initial
      description four decades ago. Failure in unsedated diagnostic cases due to
      patient pain led to the introduction of sedation. Extension to screening cases,
      albeit logical, created a sedation-related barrier to colonoscopy screening. In
      recent years a water method has been developed to combat the pain during
      unsedated colonoscopy in the US. In randomized controlled trials the water method
      decreases pain, increases cecal intubation success, and enhances the proportion
      of patients who complete unsedated colonoscopy. The salvage cleansing of
      suboptimal bowel preparation by the water method serendipitously may have
      increased the detection of adenoma in both unsedated and sedated patients. The
      state-of-the-art lecture concludes that unsedated colonoscopy is feasible. The
      hypothesis is that recent advances, such as the development of the water method,
      may contribute to reviving unsedated colonoscopy as a potentially attractive
      option for colon cancer screening and deserves to be tested.

PMID- 21727741
TI  - A rare retroperitoneal tumor.

PMID- 21727742
TI  - Chronic abdominal pain in a child.

PMID- 21727743
TI  - SMAD4 promoter hypermethylation in Kashmiri colorectal cancer cases.

PMID- 21727744
TI  - Massive rectal bleeding: rare presentation of circumferential solitary rectal
      ulcer syndrome.

PMID- 21727745
TI  - Double inferior vena cava mimicking lymphadenopathy.

PMID- 21727746
TI  - Acute myeloid leukemia post-allogeneic peripheral stem cell transplant with
      gastric chloroma.

PMID- 21727748
TI  - Glycogen hepatopathy in a 13-year-old male with type 1 diabetes.
AB  - Glycogenic hepatopathy (GH ) is a rare cause of serum transaminase elevations in
      type 1 diabetes mellitus. We describe a 13-year-old male with a history of poorly
      controlled type 1 diabetes mellitus who presented with hepatomegaly and severe
      transaminase flares. Liver histology confirmed GH. Treatment consists of
      improving glycemic control. Hepatomegaly due to excess glycogen storage in poorly
      controlled type 1 diabetics has been associated with younger patients with poor
      glycemic control, occurring about 2-4 weeks after starting insulin treatment, and
      resolving upon glucose stabilization. We conclude that glycogenic hepatopathy can
      cause hepatomegaly and significant transaminase elevations in individuals with
      type I diabetes mellitus, The recovery of severe transaminase elevations in this
      patient illustrates the more benign course of GH, which is a condition with a far
      better prognosis. Clinician awareness of GH should prevent diagnostic delay and
      will provide better insight into the prevalence of GH.

PMID- 21727749
TI  - Diabetes and Ramadan: an update on use of glycemic therapies during fasting.
AB  - The fasting of Ramadan is observed by a large proportion of Muslims with
      diabetes. Recommendations for the management of diabetes during Ramadan were last
      published in 2005 by the American Diabetes Association. Several studies in this
      field have since been published, some addressing the use of new pharmacological
      agents in managing diabetes during Ramadan. The incritin memetics are potentially
      safe during Ramadan; the DPP4 inhibitors vildagliptin and sitagliptin provide an
      effective and safe therapeutic option, administered either alone or in
      combination with metformin or sulfonylureas. There are no published studies on
      the use of GLP-1 receptor agonists during Ramadan. Among the sulfonylureas,
      gliclazide MR (modified release) and glimepride can be safely used during
      Ramadan, but glibenclamide should be avoided due to the associated risk of
      hypoglycemia. In selected patients with type 1 and type 2 diabetes, the long
      acting insulin analogues glargine and detemir, as well as the premixed insulin
      analogues, can be used with minimal risk of metabolic derangement or
      hypoglycemia; the risk is higher in type 1 diabetes. Insulin pumps can
      potentially empower patients with diabetes and enable safe fasting during the
      month of Ramadan. Further clinical trials are needed to evaluate the safety and
      efficacy of new antidiabetic agents and new diabetes-related technologies during
      Ramadan.

PMID- 21727750
TI  - Remote ischemic preconditioning. -Is it time to introduce it in clinical
      practice?-.

PMID- 21727751
TI  - Critical myocardial ischemia. -Visually homogeneous but heterogeneous through
      "21st century echo eyes"-.

PMID- 21727752
TI  - Is hypertensive disorder a unique risk factor for peripartum cardiomyopathy and
      pregnancy-associated cardiomyopathy?

PMID- 21727753
TI  - Improving quality of care and outcomes for heart failure. -Role of registries-.
AB  - Heart failure (HF) results in substantial morbidity, mortality, and costs, yet
      quality of care varies widely and is frequently inadequate. Performance
      improvement registries have been developed to improve the quality of care and
      outcomes for patients with HF in both the inpatient and outpatient settings. HF
      registries in the United States include ADHERE, OPTIMIZE-HF, GWTG-HF, and IMPROVE
      HF. These registries collect data on clinical characteristics, admission,
      hospital, discharge, and/or outpatient care, as well as outcomes. Web-based tools
      that provide real-time feedback of performance and other quality measures
      benchmarked to other sites and national data are frequently utilized. Process-of
      care improvement tools, including evidence-based clinical decision support,
      customizable order sets, and patient education are also used. Participation in
      performance improvement registries has been associated with substantial
      improvements in the use of guideline-recommended therapies for HF in both the
      inpatient and outpatient settings. Conformity with HF quality measures has also
      been shown to improve and disparities in care have also been reduced or
      eliminated. There have also been improvements in clinical outcomes. This paper
      reviews the evidence that participation in HF performance improvement registries
      is associated with improved use of guideline-recommended HF therapies, better
      conformity with quality measures, and improved outcomes in patients with HF.

PMID- 21727754
TI  - Correlation of intrinsic in vitro and in vivo clearance for drugs metabolized by
      hepatic UDP-glucuronosyltransferases in rats.
AB  - A method for quantitatively predicting the hepatic clearance of drugs by UDP
      glucuronosyltransferases (UGTs) from in vitro data has not yet been established.
      We examined the relationship between in vitro and in vivo intrinsic clearance by
      rat hepatic UGTs using 10 drugs. For these 10 drugs, the in vitro intrinsic
      clearance by UGTs (CL(int, in vitro)) measured using alamethicin-activated rat
      liver microsomes was in the range 0.10-4500 ml/min/kg. Microsomal binding (f(u,
      mic)) was determined to be in the range 0.29-0.95 and the unbound intrinsic
      clearance (CL(uint, in vitro)) to be in the range 0.11-9600 ml/min/kg. The
      contribution of rat hepatic glucuronidation to drug elimination was 12.0%-76.6%
      and in vivo intrinsic clearance by UGTs was 5.7-9000 ml/min/kg. To evaluate the
      discrepancy between the in vitro and in vivo values, a scaling factor was
      calculated (CL(int, in vivo)/CL(int, in vitro)); the values were found to be in
      the range 0.89-110. The average fold error of the scaling factor values
      incorporating f(u, mic) was closer to unity than that without f(u, mic). The
      scaling factor values incorporating f(u, mic) were <10 in 8/10 drugs and <2 in
      6/10 drugs, indicating a small discrepancy between in vitro and in vivo values.
      Thus, using alamethicin-activated liver microsomes, incorporating f(u, mic) into
      CL(int, in vitro), and considering the contribution of glucuronidation may enable
      us to quantitatively predict in vivo hepatic glucuronidation from in vitro data.

PMID- 21727755
TI  - Effect of genetic polymorphisms of SLC28A1, ABCG2, and ABCC4 on bioavailability
      of mizoribine in healthy Japanese males.
AB  - The aim of the present study was to investigate the genetic factors responsible
      for the interindividual variability in the bioavailability of mizoribine. Thirty
      healthy Japanese men aged 20-49 years and weighing 53-75 kg participated in the
      present study and took 150 mg of mizoribine. Urine samples were collected
      periodically for 12 h after the dose, and the bioavailability of mizoribine was
      calculated from the estimated total urinary excretion from time zero to infinity.
      The bioavailability of mizoribine in the 30 subjects ranged from 60.3% to 99.4%.
      The mean bioavailability of mizoribine in subjects with the concentrative
      nucleoside transporter 1 (SLC28A1) 565-A/A allele (75.4%) was significantly lower
      than that in subjects with the SLC28A1 565-G/G allele (90.1%). On the other hand,
      the bioavailability of mizoribine was not affected by polymorphisms of breast
      cancer resistance protein (ABCG2) C421A and multidrug resistance-associated
      protein 4 (ABCC4) G2269A. The findings in the present prospective study suggested
      that the genetic test for the SLC28A1 G565A polymorphism is promising for
      predicting the Japanese subjects with lower bioavailability of mizoribine.

PMID- 21727756
TI  - An alternative protein standard to measure activity of LOX-1 ligand containing
      apoB (LAB) - utilization of anti-LOX-1 single- chain antibody fused to apoB
      fragment.
AB  - AIM: We have recently demonstrated that the circulating level of LOX-1 ligand
      containing apoB (LAB) predicts the risk of cardiovascular events; however, as is
      the case in other assays measuring oxidized LDL (oxLDL), chemical unstability and
      inter-lot variance of standard oxLDL may limit the utility of measuring LAB. This
      study aimed to develop an alternative protein standard that is simultaneously
      recognized by LOX-1 and anti-apoB antibody instead of copper-oxidized LDL.
      METHODS AND RESULTS: cDNAs encoding the variable regions of anti-LOX-1 monoclonal
      antibody were cloned from hybridomas and reorganized to express anti-LOX-1 single
      chain variable fragment (Fv). cDNAs of four regions of human apoB (B1 to B4),
      which were reported to be epitopes of many anti-apoB antibodies, were also
      cloned. After confirming the respective reactivity of Fv and apoB fragments to
      LOX-1 and anti-apoB antibodies, cDNAs of Fv and apoB fragments were connected to
      express Fv-ApoB chimeric proteins. These fusion proteins were found to be
      recognized by both LOX-1 and anti-apoB antibodies. Among them, the fusion
      proteins of Fv-B1 and Fv-B3 gave saturable binding curves against immobilized LOX
      1 when detected by anti-apoB antibodies. The binding curves of different Fv-B1
      preparations to LOX-1 were almost identical while those of oxLDL varied among the
      preparations, suggesting better quality control of Fv-B1 preparations.
      CONCLUSIONS: The fusion proteins composed of Fv-form anti-LOX-1 antibody and apoB
      fragment are useful alternatives to copper-oxidized LDL in determining LAB, which
      would facilitate the application of modified LDL analyses to the clinical
      diagnosis and risk evaluation of cardiovascular disease.

PMID- 21727757
TI  - Effect of recovery from obesity on cardiovascular risk factors among Japanese
      schoolchildren: the Iwata population-based follow-up study.
AB  - BACKGROUND: The effect of recovery from obesity on cardiovascular risk factors is
      not well understood in Japanese children. METHODS: We analyzed follow-up data
      from the Iwata city population-based study of schoolchildren in Japan. The Iwata
      Board of Education conducted health screenings of children aged 10 and 14 years.
      A total of 914 children aged 10 years (451 boys and 463 girls, 87.1% of all
      children in the city in 1997) were followed until 14 years of age and classified
      by pattern of obesity as Normal, Recovered, Worsened, or Persistent. RESULTS: Of
      the 914 children, 111 (12%) were obese at 10 years of age. Of those children, 44
      (40%) were no longer obese at 14 years (ie, Recovered). At follow-up, Recovered
      boys had the greatest decrease in non-HDL cholesterol (mean +/- SE, -21.3 +/- 3.6
      mg/dL) among the 4 groups, and Recovered girls had a significantly lower level of
      non-HDL cholesterol (Recovered, 107.1 +/- 5.4 mg/dL vs. Persistent, 126.1 +/- 4.5
      mg/dL). The Recovered boys also had a significantly higher level of HDL
      cholesterol at age 14 (Recovered, 67.2 +/- 2.7 mg/dL vs. Persistent, 53.3 +/- 2.1
      mg/dL). In the Recovered group, 68% of children who were dyslipidemic at baseline
      had normal cholesterol levels at age 14. The recovery rate from dyslipidemia was
      significantly higher in the Recovered group (cumulative incidence rate ratio,
      2.5; 95% confidence interval, 1.4-4.7) as compared with the Persistent group.
      CONCLUSIONS: Dyslipidemia was reversed in children who recovered from obesity.
      Our findings suggest that reducing obesity is beneficial to the health of
      Japanese schoolchildren.

PMID- 21727758
TI  - Long-term effects of home-based bench-stepping exercise training on healthcare
      expenditure for elderly Japanese.
AB  - BACKGROUND: We examined the long-term effects of home-based bench-stepping
      exercise training on total healthcare expenditure (TOHEX) and number of
      outpatient visits (NOVIS) in elderly adults. METHODS: A total of 189 elderly
      Japanese (age 73 +/- 4 years) participated in this study. They were randomly
      assigned to either an exercise or control group. TOHEX, NOVIS, and outpatient
      expenditure (OPEX) were evaluated every 6 months from 1 year before the start to
      the end of the intervention period, as well as 1 year after the end of the
      intervention. The exercise group was encouraged to perform home-based bench
      stepping exercise training on most, and preferably all, days of the week for 18
      months. RESULTS: The exercise group showed significant increases in lactate
      threshold as compared with pre-intervention values. There were no significant
      differences in TOHEX, OPEX, or NOVIS between the exercise and control groups 1
      year before the start of the intervention, and the values remained similar during
      the first 12 months of the intervention period. However, at 18 months, TOHEX,
      NOVIS, and OPEX were significantly lower in the exercise group than in the
      control group (TOHEX: 170 007 +/- 192 072 vs. 294 705 +/- 432 314 yen, P = 0.008;
      NOVIS: 19.2 +/- 26.3 vs. 28.2 +/- 32.1 days, P = 0.012; OPEX: 132 973 +/- 132 016
      vs. 187 799 +/- 158 167 yen, P = 0.005). CONCLUSIONS: The data indicate that a
      long-term home-based bench-stepping exercise program can reduce healthcare
      expenditure in elderly Japanese.

PMID- 21727759
TI  - Molecular characterization of soil bacterial community in a perhumid, low
      mountain forest.
AB  - Forest disturbance often results in changes in soil properties and microbial
      communities. In the present study, we characterized a soil bacterial community
      subjected to disturbance using 16S rRNA gene clone libraries. The community was
      from a disturbed broad-leaved, low mountain forest ecosystem at Huoshaoliao (HSL)
      located in northern Taiwan. This locality receives more than 4,000 mm annual
      precipitation, one of the highest precipitations in Taiwan. Based on the Shannon
      diversity index, Chao1 estimator, richness and rarefaction curve analysis, the
      bacterial community in HSL forest soils was more diverse than those previously
      investigated in natural and disturbed forest soils with colder or less humid
      weather conditions. Analysis of molecular variance also revealed that the
      bacterial community in disturbed soils significantly differed from natural forest
      soils. Most of the abundant operational taxonomic units (OTUs) in the disturbed
      soil community at HSL were less abundant or absent in other soils. The
      disturbances influenced the composition of bacterial communities in natural and
      disturbed forests and increased the diversity of the disturbed forest soil
      community. Furthermore, the warmer and humid weather conditions could also
      increase community diversity in HSL soils.

PMID- 21727760
TI  - Effects of angiotensin receptor blocker and calcium channel blocker on
      experimental abdominal aortic aneurysms in a hamster model.
AB  - Remodeling in the abdominal aortic wall results in abdominal aortic aneurysm
      (AAA) formation. Many patients with AAA are prescribed antihypertensive drugs.
      However, the effects of antihypertensive drugs other than their effects on blood
      pressure control are rarely reported. In this study, we investigated the effects
      of these drugs on changes in the levels of matrix metalloproteinases (MMPs) and
      on AAA formation. Experimental AAAs were created in a hamster model by wrapping
      the abdominal aorta with elastase gauze. Olmesartan medoxomil (angiotensin II
      receptor antagonist) or azelnidipine (calcium channel antagonist) was
      administered to the hamsters and then we evaluated the aortic diameter, performed
      histological analysis, and analyzed the production of MMP-2 and MMP-9 by gelatin
      zymography. The expansion rate of the aortic diameter was smaller in both
      treatment groups than in the control group. Elastica van Gieson (EVG) staining
      showed structural preservation of elastin lamellae in both treatment groups. The
      active MMP-9 level decreased in both the olmesartan group and the azelnidipine
      group. Reducing MMP-9 production is important for suppression of AAA formation.
      Both olmesartan medoxomil and azelnidipine decreased MMP-9 activity, which
      suppressed degradation of the MMPs and inhibited AAA formation. There are
      different cascades that determine the production of MMP-9.

PMID- 21727761
TI  - Analysis of subendothelial leukocyte infiltration in the trabecular veins of
      septic spleen.
AB  - The splenic white pulp (WP) consists of CD20-positive lymph follicles (LFs) and
      CD3-positive periarteriolar lymphoid sheaths. Atrophy of the WP associated with a
      prolonged period of sepsis is a well-known pathological finding at autopsy. On
      the other hand, dense subendothelial leukocyte infiltration in the trabecular
      veins is also commonly observed in autopsy specimens of septic spleen. However,
      the characteristics and significance of this finding have not yet been well
      studied. In this study, autopsy spleens obtained from 55 sepsis and 45 non-sepsis
      patients were compared to determine the clinicopathological characteristics of
      subendothelial leukocyte infiltration in the trabecular veins, and its
      pathological significance was discussed. Severe and mild subendothelial leukocyte
      infiltration in the trabecular veins was observed in 45.5% of sepsis patients,
      but was absent in non-sepsis patients. Several clinicopathological
      characteristics of subendothelial leukocyte infiltration were identified.
      Firstly, the majority of infiltrated cells were lymphocytes. Secondly, both
      incidence and degree of infiltration were decreased at the late phase of sepsis
      accompanied by atrophy of the WP. Thirdly, types and compositions of infiltrated
      leukocytes reflected the histological findings of the spleen. Thus, the
      percentage of CD20-positive cells in the infiltrating cells into the
      subendothelium was proportional to the relative size of the CD20-positive area in
      the specimen, and the percentage of MUM1-p-positive cells in the infiltrating
      cells was proportional to the frequency of appearance of MUM1-p-positive cells in
      the red pulp. The CD20-positive area approximated the relative size of the WP in
      the septic cases, while the frequency of appearance of MUM1-p-positive cells was
      indicative of the differentiation levels of LFs into plasma cells upon antigen
      stimulation. Lastly, the intense subendothelial infiltration of CD20-positive
      cells was specific for the early stage of sepsis, and the morphological
      characteristics of these CD20-positive cells suggested their association with the
      marginal zone. Based on these clinicopathological characteristics and the fact
      that leukocyte infiltration into the subendothelium of trabecular veins became
      undetectable as atrophy of the WP progressed, it was suggested that the
      infiltrating cells had migrated from the WP, and this cell infiltration is an
      early activated immunological reaction in the spleen. Furthermore, the presence
      of possible efflux or drainage routes in the subendothelial spaces of trabecular
      veins was suggested.

PMID- 21727762
TI  - Cerebrospinal fluid following cerebral ischemia accelerates the proliferation of
      bone marrow stromal cells in vitro.
AB  - The central nervous system in the embryo develops around the cerebrospinal fluid
      (CSF), which regulates cell proliferation and differentiation. Neurogenesis has
      been also reported in the subventricular zone (SVZ), which is close to CSF, after
      stroke in rats. In this study, CSF extracted following stroke in rats was added
      to bone marrow stromal cell (MSC) culture in vitro, and the proliferation and
      differentiation of MSCs were studied. Primary cultures of MSCs were obtained from
      7-week-old Lewis rats and incubated in a plastic tissue culture flask. CSF was
      retrieved from other rats 48 hrs after 0, 15 and 75 min after middle cerebral
      artery occlusion (MCAO). CSF from these three groups were added to respective MSC
      culture solutions, and the cells were then incubated for 72 hrs. Western blots of
      the extracellular signal-regulated kinase-1 and -2 (Erk1/2) were obtained just
      after the CSF induction. The expressions of CD34, CD45, CD90 and CD108 were
      assessed by flow cytometric analysis. The proliferation of MSCs was accelerated
      by the addition of post-stroke CSF, especially in the 15-min MCAO, in a dose
      dependent manner. The morphology and surface antigens of the cells were
      maintained in all groups. Phosphorylated-Erk1/2 was elevated in all the CSF
      treated groups, although this effect was more enhanced in the 15-min MCAO group.
      Our data indicate that the addition of post-stroke CSF to the primary medium
      stimulated the proliferation of MSCs, and that these MSCs maintained their
      characteristics through the p-Erk1/2 pathway. These results suggest that use of
      post-stroke CSF as a component of culture media could facilitate the autologous
      transplantation of MSCs.

PMID- 21727763
TI  - Methylphenidate enhances inhibitory synaptic transmission by increasing the
      content of norepinephrine in the locus coeruleus of juvenile rats.
AB  - The present study examined the effect of methylphenidate (MPH), a
      psychostimulant, on nor-adrenergic transmission in the locus coeruleus (LC) of
      juvenile rats. Intracellular recordings showed that MPH (>3 uM) produced a
      hyperpolarizing response associated with a decrease in the rate of spontaneously
      firing action potentials. MPH (1 uM) enhanced the amplitude of the inhibitory
      postsynaptic potential (IPSP) mediated by norepinephrine (NE), but did not change
      the excitatory postsynaptic potential (EPSP) mediated by excitatory amino acids.
      Whole-cell patch-clamp recordings showed that MPH (0.3-30 uM) produced an outward
      current (I(MPH)) and enhanced the inhibitory postsynaptic current (IPSC) in
      neurons of the juvenile rat LC. MPH (30 uM) enhanced the NE-induced outward
      current (I(NE)). Bath-application of yohimbine (1 uM) produced an inward current
      and blocked the MPH-induced enhancement of the IPSC. Yohimbine (1 uM) depressed
      not only the I(NE) but also the I(MPH) in juvenile rat LC neurons. The current
      voltage relationship of the I(MPH) showed inward rectification and reversed
      polarity at -91.1+/-4.3 mV (n=5). Ba(2+) (100 uM) blocked the I(MPH), indicating
      that the I(MPH) is mediated by Ba(2+)-sensitive inward rectifier K(+) current.
      These results suggest that MPH enhances inhibitory synaptic transmission by
      increasing the concentration of NE at noradrenergic synapses in juvenile rat LC
      neurons.

PMID- 21727764
TI  - A case of brain metastasis from pulmonary giant cell carcinoma.
AB  - A 74-year old female was admitted to our hospital due to sudden right
      hemiparesis. Precontrast brain computed tomography (CT) revealed multiple high
      density masses consistent with multiple hemorrhage, and chest CT scan
      demonstrated a mass in the left lung field without hemorrhage. Follow-up CT
      showed enlargement of the multiple intracerebral hemorrhages. A diagnosis was
      made of brain metastasis from a rare pure giant cell carcinoma (GCC) of the lung.

PMID- 21727765
TI  - Viral-associated thrombotic microangiopathies.
AB  - Thrombotic microangiopathies encompass a group of disorders characterized by
      microangiopathic hemolytic anemia, thrombocytopenia associated with hyaline
      thrombi (comprised primarily of platelet aggregates in the microcirculation), and
      varying degrees of end-organ failure. Many primary (genetic) and secondary
      etiological predisposing factors have been described-namely pregnancy, autoimmune
      disorders, cancer, drugs and antineoplastic therapy, bone marrow
      transplantation/solid organ transplantation, and infections. In the setting of
      infectious diseases, the association with Shiga or Shiga-like exotoxin of
      Escherichia coli 0157:h7 or Shigella dysenteriae type 1-induced typical hemolytic
      uremic syndrome is well known. Recently however, an increasing body of evidence
      suggests that viruses may also play an important role as trigger factors in the
      pathogenesis of thrombotic microangiopathies. This is a comprehensive review
      focusing on the current understanding of viral associated/induced endothelial
      stimulation and damage that ultimately leads to the development of this life
      threatening multisystemic disorder.

PMID- 21727766
TI  - Arsenic trioxide plus cisplatin/interferon alpha-2b/doxorubicin/capecitabine
      combination chemotherapy for unresectable hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The failure of existing treatments for liver cancer
      has recently been attributed to the existence of cancer stem cells, which are
      difficult to kill using current drugs due to their chemoresistant properties as
      well as their ability to stimulate neoangiogenesis. The aim of the current study
      was to evaluate in vitro the antitumor efficacy of arsenic trioxide in
      combination with conventional chemotherapy, as proposed by the concept of
      "differentiation therapy" in anticancer research. MATERIALS AND METHODS: Cancer
      stem cells showed enhanced chemoresistance to cancer drugs (carboplatin and
      doxorubicin) and had the ability to exclude rhodamine 123 dye, proving the
      existence of the multidrug resistance efflux pump. Arsenic trioxide was added
      prior to a tyrosine kinase inhibitor or to a slightly modified PIAF regimen with
      capecitabine replacing 5-fluorouracil. We also compared both cancer and normal
      stem cell lines with the hepG2 non-stem liver cancer cell line to investigate the
      differences between differentiated and more anaplastic cells. Molecular
      characterization (immunocytochemistry and RT-PCR analysis) of all the cell lines
      was carried out. RESULTS: Initially, the cells had a high proliferative
      potential, even when cultured in a medium supplemented with cytostatics,
      eliminated rhodamine 123 immediately in culture and also formed spheroids in
      suspension. The molecular characterization showed the expression of albumin,
      alpha1-antitrypsin, alpha-fetoprotein, citokeratin-18, telomerase, CD90 and
      CD133. Low concentrations of arsenic trioxide lead to morphologic differentiation
      and differentiation-associated cytochemical features, like increased sensitivity
      to cytostatic drugs. CONCLUSION: Our study suggests that arsenic trioxide
      sensitizes liver stem-like cancer cells to conventional chemotherapy. Still,
      further studies on animal models will be needed before we implement this idea in
      human clinical trials.

PMID- 21727767
TI  - Cytomegalovirus infections in unrelated cord blood transplantation in pediatric
      patients: incidence, risk factors, and outcomes.
AB  - BACKGROUND AND OBJECTIVES: Stem cells from umbilical cord blood (CB) have
      increasingly become a viable alternate source of progenitor cells for
      hematopoietic cell transplantation (HSCT). Cytomegalovirus (CMV) is thought to
      contribute significantly to HSCT morbidity and mortality. DESIGN AND SETTING:
      Retrospective case-control study in patients at tertiary care center. PATIENTS
      AND METHODS: We determined the incidence, risk factors and outcomes for CMV
      infection and disease after unrelated cord blood transplantation (UCBT) in
      children. RESULTS: Between 2003 and 2007, 73 pediatric patients underwent UCBT
      and 68% of recipients were CMV seropositive. The overall incidence of CMV
      infection, early and late CMV infection was 58.9% (43/73), 62.8% (27/43), and
      37.4% (16/43), respectively. in patients with early CMV infection, 6 of 27 (22%)
      patients progressed to develop CMV end-organ disease including pneumonitis and
      retinitis. High levels CMV antigenemia >=70 infected cells by pp65 antigenemia
      assay + PMNs, P=.237) were associated with a higher risk of progression to CMV
      disease. The development of CMV infections was higher in CMV-seropositive
      recipients (P<.001) and in those who developed graft-versus-host-diseases (GVhD)
      (P<.001). other risk factors for CMV infection include the use of high-dose
      corticosteroids (P<.001) and older age of the recipient at the time of transplant
      (P<.002). Late CMV infection was strongly associated with a previous history of
      early CMV infection (P<.001). CONCLUSION: CMV infection is a significant
      complication in UCBT recipients in pediatric patients and is associated with an
      increase in transplant-related morbidity and mortality. Risk factors for CMV
      infections after UCBT include GvHD, use of corticosteroids, underlying diseases
      (hematologic malignancies) and older age. Late CMV infection was strongly
      associated with a previous history of CMV infection.

PMID- 21727768
TI  - Very late onset lymphoproliferative disorders occurring over 10 years post-renal
      transplantation: PTLD.Int. Survey.
AB  - BACKGROUND AND OBJECTIVES: Knowledge of the significance of post-transplant
      lymphoproliferative disorders (PTLD) that occur "very late" or more 10 years
      after renal transplantation is limited. thus, we analysed and compared
      characteristics and prognosis of the disease in renal transplant patients with
      very late onset PTLD vs. early- and late-onset PTLD. DESIGN AND SETTING:
      Retrospective study of data obtained from comprehensive search of medical
      literature PATIENTS AND METHODS: We searched for available data using the Pubmed
      and Google scholar search engines for reports of lymphoproliferative disorders
      occurring in renal transplant patients by disease presentation time. RESULTS: We
      analyzed data from 27 studies that included 303 patients with lymphoproliferative
      disorders after renal transplantation. Renal graft recipients with very late
      onset PTLD were significantly less likely to be under mycophenolate mofetil (MMF)
      and/or tacrolimus (FK-506) (vs. azathioprine) -based immunosuppression (P=.035)
      and less likely to have a history of antibody induction immunosuppression
      (P<.001). Compared to "early onset" disease, "very late" onset PTLD is more
      likely to develop in older patients (P=.032). Survival analysis did not show any
      difference in outcome (P=.5). no organ involvement priority was found for this
      patient group (P>.1 for all). CONCLUSIONS: Older renal transplant patients are at
      increased risk for development of very late onset PTLD, and should be strictly
      followed. further multi-institutional prospective studies are needed to confirm
      our results.

PMID- 21727769
TI  - Hematopoietic stem cell transplantation in the Eastern Mediterranean Region
      (EMRO) 2008-2009: report on behalf of the Eastern Mediterranean Bone Marrow
      Transplantation (EMBMT) Group.
AB  - BACKGROUND: The Eastern Mediterranean Bone Marrow Transplantation (EMBMT) Group
      has accumulated over 25 years of data and experience in hematopoietic stem cell
      transplantation (HSCT), most particularly in hemoglobinopathies, severe aplastic
      anemia (SAA), and inherited metabolic and immune disorders, in addition to
      hematologic malignancies peculiar to the region and where recent updates in
      trends in activities are warranted. OBJECTIVES: To study trends in HSCT
      activities in the World Health Organization-Eastern Mediterranean (EM) region
      surveyed by EMBMT between 2008 and 2009. STUDY DESIGN: Retrospective analysis of
      the survey data, mainly of the cumulative number of transplants, types of
      transplants (autologous vs. allogeneic), types of conditioning as myeloablative
      (MAC) vs. reduced intensity conditioning (RIC) and trends in leukemias,
      hemoglobinopathies, SAA, inherited bone marrow failure syndromes amongst others.
      RESULTS AND DISCUSSION: Fourteen teams from ten Eastern Mediterranean Region
      Organization (EMRO) countries reported their data (100% return rate) to the EMBMT
      for the years 2008-2009 with a total of 2608 first HSCT (1286 in 2008; 1322 in
      2009). Allogeneic HSCT represented the majority (63%) in both years. The main
      indications for allogeneic HSCT were acute leukemias (732; 44%), bone marrow
      failure syndromes (331, 20%), hemoglobinopathies (255; 15%) and immune
      deficiencies (90; 5%). There was a progressive increase in the proportions of
      chronic myeloid leukemia (CML) cases transplanted beyond the first chronic phase
      (3; 7% of all CML cases in 2008 vs 13; 29% in 2009). The main indications for
      autologous transplants were plasma cell disorders (345; 36%) Hodgkin disease
      (256; 27%), non-Hodgkin lymphoma (207; 22%) and solid tumors (83; 9%). RIC
      continued to show a progressive increase over the years (7% in 2007, 11% in 2008
      and 13% in 2009), yet remained relatively low compared to contemporary practices
      in Europe published by EBMT. The vast majority (95%) of allo-HSCT sources were
      from sibling donors with a continued dominance of peripheral blood (PB) (1076;
      63%), while cord blood transplant (CBT) increased to 83 (5% of allo-HSCT),
      matched unrelated donor (MUD) remained underutilized (1; 0%) and there were no
      haploidentical transplants reported. Large centers with >50 HSCT/year showed a
      plateau of the total number of allo-HSCT over the last 5 years that may be
      related to capacity issues and needs further study. CONCLUSIONS AND
      RECOMMENDATIONS: There is an overall increased rate of HSCT in the EMRO region
      with a significant increase in utilization of CBT and allogeneic PB-HSCT as a
      valuable source. However, further research on outcome data and development of
      regional donor banks (CB and MUD) may help facilitate future planning to satisfy
      the regional needs and increase collaboration within the group and globally.

PMID- 21727770
TI  - Rosai-Dorfman disease of the paranasal sinuses and orbit.
AB  - Rosai-Dorfman disease, also known as sinus histiocytosis with massive
      lymphadenopathy, is a benign indolent disorder, characterized by enlarged lymph
      nodes filled with histiocytes. Extranodal involvement is uncommon. The disease
      rarely affects the nose and paranasal sinuses. We report a case that presented
      with a right nasal mass, extending into all the paranasal sinuses and right orbit
      without any accompanying lymphadenopathy. Because of the absence of
      lymphadenopathy it posed a diagnostic challenge until the pathology was confirmed
      on histopathological examination.

PMID- 21727771
TI  - Complete recovery following sudden sensorineural hearing loss in a patient with
      sickle cell disease.
AB  - A sickle cell disease (SCD) patient with vaso-occlusive crisis (VOC) developed
      sudden senserinural hearing loss (SNHL), which responded well to a rapid course
      of corticosteroids along with exchange transfusions. The otolaryngologist should
      be aware of the otologic manifestations of SCD such as SNHL. A good response to
      steroids, which averted a permanent hearing loss, warrants further studies to
      define the augmentive benefits of such therapy along with exchange transfusions
      in patients with SCD in VOC who develop sudden SNHL.

PMID- 21727772
TI  - Successful treatment of steroid-refractory autoimmune thrombocytopenia associated
      with Castleman disease with anti-CD-20 antibody (rituximab).
AB  - Multicentric Castleman disease (MCD) is a lymphoproliferative disorder of
      incompletely understood etiology and with various clinical presentations. The
      best therapeutic option for this disease is not well established. MCD is known to
      be associated with autoimmune phenomena. A 70-year-old female patient of MCD with
      progressive nodal disease associated with autoimmune thrombocytopenia failed
      steroid treatment and showed a transient response to intravenous immunoglobulin.
      The patient achieved complete recovery of her platelet count and a very good
      response in nodal disease after 3 weekly doses of anti-CD-20 antibody
      (rituximab). Anti-CD20 antibody treatment could be a good therapeutic option for
      MCD, mainly when associated with immune-related disorders.

PMID- 21727773
TI  - Untreated primary thyroid lymphoma in an elderly woman.

PMID- 21727774
TI  - Hepatocellular carcinoma to renal cell carcinoma metastasis: a rare phenomenon
      with diagnostic challenges.

PMID- 21727775
TI  - CD123 monoclonal antibody in myelodysplastic syndrome.

PMID- 21727776
TI  - How do eating disorder patients eat after treatment? Dietary habits and eating
      behaviour three years after entering treatment.
AB  - OBJECTIVE: Improvements in psychological symptoms and weight have often been
      demonstrated following eating disorder (ED) treatment, but it is not clear to
      what extent eating behaviour itself is normalised. This cross-sectional study
      aimed to investigate dietary habits and eating behaviour in ED patients three
      years after entering treatment. METHOD: ED patients (N=70) were divided into
      those who had recovered (N=36), and those who still suffered from bulimic (N=18)
      or anorexic (N=16) psychopathology. Patients were compared to a female normal
      control group of similar age (N=61), and assessments were made on a dietary
      questionnaire, as well as the BDI, EDI-2, SASB and SCL-90. RESULTS: With some
      notable exceptions eating patterns in recovered patients resembled those of
      controls. Dieting was most evident in recovered and current bulimic patients,
      while restrictive eating and vegetarianism was found in recovered or current
      anorexic patients. A majority of the patients with ongoing EDs avoided fatty
      foods. DISCUSSION: Risk behaviours such as restrictive eating, dieting and food
      avoidance, may have an important impact on relapse rates, and it may therefore be
      imperative to continue to monitor eating behaviour in ED patients following
      treatment termination to ensure better long-term outcome.

PMID- 21727777
TI  - Coping responses as mediators in the relationship between perceived weight stigma
      and depression.
AB  - The prejudice and discrimination that overweight and obese individuals experience
      as a result of their weight (i.e. weight stigma) often leads to psychological
      consequences, such as depression. The present study examined whether coping with
      stigmatizing experiences mediated the relationship between perceived weight
      stigma and depression among overweight/obese treatment seeking adults. Fifty-four
      overweight and obese (mean BMI=37.2) weight loss treatment seeking participants
      (87.3% Caucasian, 79.6% female) participated in the study. Results from this
      study indicate that greater stigmatizing experiences were significantly related
      to depression. Both adaptive and maladaptive coping significantly mediated the
      relationship between weight stigma and depression. Surprisingly however, greater
      adaptive coping was positively related to depression. Coping responses appear to
      mediate the association between experiencing bias and discrimination because of
      one's weight and adverse psychological outcomes. Results suggest that obese
      individuals are at considerable risk for psychological complications secondary to
      weight-based mistreatment by others and their responses to cope with the
      mistreatment.

PMID- 21727778
TI  - Evaluation of alexithymia and depression in severe obese patients not affected by
      eating disorders.
AB  - OBJECTIVE: The main purpose of this study is to evaluate the different aspects of
      the construct of alexithymia in a group of severe obese patients not affected by
      eating disorders. Moreover, we tested if in the same patients there was a
      relationship between alexithymic traits and depressive symptoms. METHOD: Forty
      nine severe obese patients were evaluated through the Toronto Alexithymia Scale
      (TAS-20) and the Beck Depression Inventory (BDI). The results were compared with
      those of a normal weight control group. RESULTS: Obese patients were less able
      than control subjects in recognizing and labeling their own emotions. This
      deficit was positively associated with depressive symptoms. CONCLUSIONS: The data
      suggest that severe obese patients have more difficulties in recognizing their
      emotions and have more depressive symptoms than control subjects have.

PMID- 21727779
TI  - Threshold and subthreshold post-traumatic stress disorder in bulimic patients:
      prevalences and clinical correlates.
AB  - OBJECTIVE: Post-traumatic stress disorder (PTSD) is believed to impact the
      clinical presentation and treatment response in bulimia nervosa (BN), but
      available data do not clarify the clinical implications of subthreshold forms of
      PTSD, believed to affect a sizable proportion of bulimic women. METHOD: In 78
      women with BN and 61 women who ate normally, we assessed lifetime rates of
      threshold and subthreshold PTSD, and examined clinical correlates. RESULTS: Among
      bulimic women, rate of threshold PTSD was 17.9% and rate of a formally-defined,
      subthreshold PTSD syndrome was 41.0%. Bulimic women with subthreshold PTSD did
      not differ from women with threshold PTSD on any clinical indices (except
      generalized anxiety disorder) and both groups with a PTSD-spectrum syndrome
      displayed worse psychiatric symptoms than did bulimic women without PTSD
      symptoms. DISCUSSION: Threshold and subthreshold variants of PTSD occur
      substantially more frequently among bulimic women than they do among normal-eater
      women. Intriguingly, bulimic women with subthreshold PTSD appear to be at similar
      risk for psychiatric morbidity as are those with threshold PTSD. The preceding
      suggests that formal, categorical concepts of PTSD may not fully reflect
      important trauma correlates seen in women with BN.

PMID- 21727780
TI  - Perfectionism as a mediator between perceived criticism and eating disorders.
AB  - OBJECTIVE: In this work we aimed to test the hypothesis that perfectionism plays
      a third variable role in the psychological process leading from perceived
      criticism to eating disorders (ED). METHOD: Forty-nine individuals with ED and 49
      controls completed the Concern over Mistakes subscale of the Multidimensional
      Perfectionism Scale, the Perceived Criticism Inventory, and the Drive for
      Thinness, Bulimia, and Body Dissatisfaction subscales of the Eating Disorders
      Inventory. Mediational and moderational models were tested. RESULTS: Analyses
      revealed that perfectionism mediates between perceived criticism and drive for
      thinness. Results for bulimia and body dissatisfaction were controversial.
      Moderational models were rejected. DISCUSSION: Results suggest that restrictive
      dieting is related to a process in which perceived criticism is the initial
      factor and perfectionism is an intervening mediator.

PMID- 21727781
TI  - Immediate cognitive effects of repetitive Transcranial Magnetic Stimulation in
      eating disorders: a pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of high frequency
      repetitive Transcranial Magnetic Stimulation (rTMS), delivered to the
      dorsolateral prefrontal cortex, on selective attention in people with a bulimic
      disorder. METHOD: Participants (N=33) were randomised to a single session of real
      or sham rTMS. They performed a Stroop colour word task before and after the rTMS
      intervention. Interference scores were calculated as the time difference between
      completing cards with congruent and incongruent stimuli. RESULTS: Analysis of
      covariance comparing the interference scores post-rTMS with the pre-rTMS scores
      as covariates showed no differences between the real and sham groups
      [F(1,32)=1.110; p=0.301]. DISCUSSION: While methodological issues warrant a
      cautious interpretation, these pilot data suggest that selective attention is
      unaffected by a single session of rTMS.

PMID- 21727782
TI  - Dysfunctional metacognitions in anorexia nervosa.
AB  - OBJECTIVE: The aim was to compare women with anorexia nervosa (AN) and without AN
      in terms of dysfunctional metacognitions. METHOD: 167 Australian women with AN
      (N=74; mean age 24.3 yrs) and without AN (N=93; mean age 27.3 yrs) completed the
      Metacognitions Questionnaire-30. RESULTS: Multivariate analyses revealed that
      relative to controls, AN patients had higher scores on metacognitive dysfunction:
      they exhibited low confidence in their cognitive competence, reported obsessively
      monitoring and striving to control their thoughts, and held negative beliefs
      about the danger of worrying. Furthermore, this was not due to starvation
      effects. However, patients did not exhibit significantly more positive beliefs
      about worry than controls once body mass index had been controlled. CONCLUSION:
      Metacognitive dysfunction may play a key role in the maintenance of AN;
      therefore, metacognitive therapy may be usefully applied to its treatment.

PMID- 21727783
TI  - Adolescent development and eating disorder related quality of life in Indian
      females.
AB  - OBJECTIVE: To study the relationship of adolescent development and eating
      disorder related quality of life in Indian females. METHOD: 461 female school
      students (aged 12-17 yrs) were recruited from middle to high socio-economic
      status (SES), English speaking schools in Delhi, India. Adolescent development
      was measured by Tanner stage and months since menarche. Subjects completed the
      Quality of Life for Eating Disorders questionnaire (QOL ED), which included six
      subscores. Correlation and partial correlation coefficient analysis to control
      for Body Mass Index (BMI) were performed. RESULTS: After controlling for BMI, all
      adolescent development measures were correlated with the psychological feelings
      (PSY) subscore. This subscore contained items relating to confusion, social
      unease, sadness, difficulty coping, desiring perfection and loss of control.
      Tanner breast stage was correlated with the eating behaviour (EB) subscore.
      DISCUSSION: During adolescent development, Indian girls became more aware of
      their psychological feelings and emotions. Only those reporting breast
      development were using behaviours to control their body, weight and shape. These
      behaviours are not associated with the presence of disordered eating thoughts,
      such as preoccupation with food, eating, body weight or shape.

PMID- 21727784
TI  - Is being underweight associated with impairments in quality of life in the
      absence of significant eating disorder pathology?
AB  - Few studies have compared low-weight individuals with eating disorder (ED)
      pathology with similar-weight individuals without significant pathology despite
      the fact that body weight is often used as a key outcome within ED research. This
      study compared quality of life (QoL) in one group with high levels of ED
      pathology to a group with low ED pathology, matched by body mass index (BMI). The
      high ED group reported significantly lower ED-specific quality of life (EDQoL)
      than the low ED group. These findings suggest that young women with high levels
      of ED pathology report significantly more impaired QoL than comparable young
      women with no ED pathology, and that being underweight alone is not a primary
      contributor to poorer EDQoL.

PMID- 21727785
TI  - An exploratory study of eating disorder psychopathology among Overeaters
      Anonymous members.
AB  - Overeaters Anonymous (OA) is a widely available, 12-step, self-help treatment
      program primarily used for weight loss that also offers to address eating
      disorder (ED) symptoms. However, because of OA's tradition of avoiding contact
      with "outside enterprises," little research has examined eating pathology among
      OA members. The present, uncontroled study examined current, self-reported ED
      psychopathology with the Eating Disorder Examination Questionnaire among 20 self
      selected OA members. Consistent with OA's aim to address compulsive overeating,
      rates of subjective and objective bulimic episodes and eating concern were
      significantly elevated among OA members relative to norms for adult women,
      demonstrating medium effects, and restraint showed a significant, small effect.
      Other ED symptoms, including weight concern and compensatory behaviors, were not
      statistically different from norms, yet demonstrated small effect sizes. We
      conclude that many OA members may experience ED psychopathology that extends
      beyond binge eating.

PMID- 21727787
TI  - Maggie's maladies.

PMID- 21727786
TI  - The mediational significance of negative/depressive affect in the relationship of
      childhood maltreatment and eating disorder features in adolescent psychiatric
      inpatients.
AB  - OBJECTIVE: Childhood maltreatment is a risk factor for eating disorder and
      negative/depressive affect appears to mediate this relation. However, the
      specific elements of eating- and body-related psychopathology that are influenced
      by various forms of childhood maltreatment remain unclear, and investigations
      among adolescents and men/boys have been limited. This study investigated the
      mediating role of negative affect/depression across multiple types of childhood
      maltreatment and eating disorder features in hospitalized adolescent boys and
      girls. METHOD: Participants were 148 adolescent psychiatric inpatients who
      completed an assessment battery including measures of specific forms of childhood
      maltreatment (sexual, emotional, and physical abuse), negative/depressive affect,
      and eating disorder features (dietary restriction, binge eating, and body
      dissatisfaction). RESULTS: Findings suggest that for girls, negative/depressive
      affect significantly mediates the relationships between childhood maltreatment
      and eating disorder psychopathology, although effects varied somewhat across
      types of maltreatment and eating disorder features. Generalization of mediation
      effects to boys was limited.

PMID- 21727788
TI  - Nutrition in the care of patients with cancer cachexia.
AB  - Cancer cachexia, a progressive wasting syndrome experienced by approximately 80%
      of patients, is characterized by loss of adipose tissue and lean body mass. This
      complex metabolic process reflects both reduced nutrient availability and
      increased nutritional demand. Though cachexia is most commonly associated with
      particular tumours, no patient or tumour are excluded. This article provides an
      overview of cachexia and its pathophysiology and the factors contributing to its
      development before considering its impact on individuals. Emphasis is placed on
      the nutritional aspects of its management.

PMID- 21727789
TI  - Eczema: causes, symptoms and treatment in the community.
AB  - The most common diseases encountered by health professionals are those associated
      with skin disorders. There are thousands of skin diseases, accurate diagnosis of
      which is critical to appropriate management and patient outcomes. Diseases of the
      skin are the most common group of occupational health problems that lead to
      absence from work in the general population. Eczema describes a variety of
      inflammatory skin disorders; it is a chronic, widespread, non-infective
      inflammatory condition that causes severe pruritus, erythema and scaling. The
      condition can impact at any age; generally it occurs during infancy or early
      childhood. The cause of atopic eczema is complex and not fully understood. This
      article describes the pathophysiology associated with eczema focusing upon atopic
      eczema. Signs and symptoms are described; methods of diagnosis and treatment
      options are outlined. The most up-to-date clinical evidence is used to inform the
      community nurse. The active involvement of the informed patient in their therapy
      is critical to success and this is advocated. The role of the nurse is central to
      enhancing health and wellbeing of people with atopic eczema.

PMID- 21727790
TI  - Recruiting newly qualified nurses: why student placements matter.

PMID- 21727791
TI  - Safer care at home: use of simulation training to improve standards.
AB  - One of the fundamental problems facing providers and commissioners of health
      services is how to maintain the skills and knowledge of the workforce during the
      initial development and implementation of home care services. This small-scale
      project sought to ascertain if it was possible to use human patient simulation
      scenarios to educate community nurses about how to recognize when care at home is
      appropriate and when it is not. A series of scenarios were developed and
      delivered to small groups of community nursing staff. A total of 18 qualified
      nurses took part in the project. Participants were asked to report their level of
      confidence in the diagnosis, management and recognition of patient deterioration
      for each of the scenarios prior to and after the session. The results show
      increased confidence across all participants in each of the scenarios.

PMID- 21727792
TI  - Rheumatoid arthritis: bringing care closer to home.

PMID- 21727793
TI  - Care in the community: what would happen if the lights went out?
AB  - This article reports on a student nurse project carried out on a community
      placement in respect to patients dependent on medical devices in the event of
      power cuts. The project was designed to identify relevant literature to establish
      what emergency and preparatory procedures and protocols are in place in a primary
      care trust for this type of emergency and to identify what action a nurse in the
      community should take to ensure the safety and welfare of their patients if a
      there was a prolonged power failure. The literature and knowledge of community
      staff for the correct procedures to follow in the event of a power cut in the
      community established that there was some cause for concern, and identified that
      a loss of power to a patient with a medical device poses a serious risk.
      Recommendations are that an initial risk assessment of power failure needs to be
      undertaken and included in the appropriate documentation and guidance plans
      prepared for community staff and should include the listing of the patient as
      vulnerable. The limited research identified within this project also indicates
      that contingency plans to ensure the safety and well-being of patients in the
      community clearly need to be included in disaster and emergency planning.

PMID- 21727794
TI  - Elderly still hungry to be heard: a nutrition update from Age UK.

PMID- 21727795
TI  - Leg Clubs: helping nurses improve patient outcomes.

PMID- 21727796
TI  - Modernizing public health law.
AB  - The rapid spread of a mutant strain of Escherichia coli throughout Europe
      highlights the need for modern and flexible public health laws to identify,
      control and treat infections and contamination that give significant concern for
      the health of the population. In this article, Richard Griffith and Cassam
      Tengnah outline the amendments to the Public Health (Control of Disease) Act 1984
      that adopt an all-hazards approach to threats to public health.

PMID- 21727797
TI  - Promoting healthy ageing.

PMID- 21727803
TI  - Primary bone tumours from the vertebral column.

PMID- 21727804
TI  - Epilepsy and its neuropsychiatric complications in older adults.

PMID- 21727805
TI  - Imaging of the liver: pictorial review of the most common pathologies.

PMID- 21727806
TI  - General surgery: allow its extinction or begin its revival?

PMID- 21727807
TI  - Fluid resuscitation 'post Boldt': throwing out the baby with the bathwater?

PMID- 21727809
TI  - Convex probe endobronchial ultrasound: pitfalls, training and service issues.
AB  - Convex probe endobronchial ultrasound is an evolving technology allowing real
      time transbronchial needle aspiration used for lung cancer staging and diagnosis
      of cancer or unexplained mediastinal or hilar lymphadenopathy. This article
      focuses on setting up a service, pitfalls and training issues.

PMID- 21727810
TI  - Tracheobronchial stenting.
AB  - Airway stenting can be a life-preserving intervention in patients with critical
      airway obstruction. It may be safely performed using flexible bronchoscopy under
      conscious sedation as a day-case procedure in selected patients, but a high
      incidence of complications limits its use to palliation of malignancy or bridging
      treatment in benign disease.

PMID- 21727811
TI  - Thoracic ultrasound for beginners: utility and training issues for clinicians.
AB  - Bedside thoracic ultrasound is gaining popularity among non-radiologists, because
      of its advantages in the diagnosis and management of pleural disease. However, it
      has significant potential pitfalls and formal training is essential to avoid
      harm. This review gives an overview of the utility of ultrasound and discusses
      training.

PMID- 21727812
TI  - Pleural procedures: intercostal chest drains and indwelling pleural catheters.
AB  - Drainage of pleural effusions is often necessary to keep patients symptom free.
      This article describes two methods of removing pleural fluid and outlines the
      insertion procedure. Indications, potential complications and post-procedure
      management are also discussed.

PMID- 21727813
TI  - Antimicrobial prophylaxis for the prevention of infective endocarditis.
AB  - National and international guidelines on antimicrobial prophylaxis to prevent
      infective endocarditis have provoked controversy and consternation among many
      doctors and patients. This article addresses the evidence that underlies these
      guidelines.

PMID- 21727814
TI  - Clinical leadership: the challenge of making the most of doctors in management.
AB  - The need to develop the leadership and management capability of clinicians is
      deemed fundamental to address the cost and quality issues associated with health
      care provision. The challenge facing the NHS is how best to bring this about.

PMID- 21727815
TI  - Medical leadership and the medical student.
AB  - As leadership and management are increasingly seen as a vital part of the
      doctor's daily repertoire, medical schools are starting to implement leadership
      development programmes as a routine part of the curriculum with opportunities for
      some students to take extended study in leadership.

PMID- 21727816
TI  - From symptoms to causes: progress in the treatment of neurological disease.

PMID- 21727817
TI  - Angelchik prosthesis revisited: radiological appearance mimicking a foreign body.

PMID- 21727818
TI  - Perineal hernia following abdominoperineal excision of rectum.

PMID- 21727819
TI  - Metastatic cerebral calcification.

PMID- 21727820
TI  - Camille Guerin: the 'G' in BCG.

PMID- 21727822
TI  - Management of drugs of misuse: do not forget solvents.

PMID- 21727824
TI  - Should foundation year doctors rotate through anaesthetics and critical care?

PMID- 21727829
TI  - Nanotechnology: science fiction or a future reality?

PMID- 21727830
TI  - Telehealth care - where is it going?

PMID- 21727831
TI  - Cultural diversity and dementia in Scottish care homes.
AB  - BACKGROUND: theoretical guidance and policy directives emphasize the necessity of
      considering the culturally-specific needs of health and social care service users
      as part of 'person-centred' approaches to care. This article outlines the ideas
      underpinning an ongoing PhD study of the interactions between care staff and
      residents which is aimed at gaining insights into how person-centred care is
      fulfilled for people with dementia in Scottish care homes. DISCUSSION: certain
      dynamics may constrain the deployment of culturally-meaningful care approaches
      for certain service users in Scottish care homes. These include limited
      understandings of the nature of cultural diversity in modern Scotland, failure to
      recognize the import of 'inter-generational' cultural change, lack of research
      around the interactions between staff and service users from different cultural
      backgrounds, and a sketchy demographic picture of the ethnic/cultural composition
      of Scottish care home populations. Groups of service users in particular settings
      (such as older people with dementia in long-term care) may be especially
      vulnerable to the effects of care processes constituted under such circumstances.
      CONCLUSION: poorly recognized gaps in understanding of the sociocultural and
      historical influences which help constitute 'the person' in many Scottish care
      home residents may exist. If these are found to constrain 'knowing the person',
      can the term 'person-centred' be meaningfully applied to care?

PMID- 21727832
TI  - Incontinence in patients with dementia.
AB  - The high prevalence of incontinence in dementia sufferers will only increase as
      the population ages (Alzheimer's Society, 2007), but the evidence-based knowledge
      for management of these long-term disorders combined is lacking (Hagglund, 2010).
      Management techniques for incontinence need to be developed to ensure that
      dementia patients receive the best care, as current methods such as behavioural
      techniques may not be appropriate for people with limited cognitive function.
      This article will address issues that arise with current incontinence management
      for dementia sufferers and possible courses of action to tailor them more
      specifically to those people with cognitive impairment. Quite often, incontinence
      is just managed with incontinence pads and treatment is not discussed, which can
      have detrimental effects on the patient (Omli et al, 2010). Nurses have an
      important role in incontinence treatment and can change this misuse of
      incontinence pads and ensuring a holistic approach to care will help when
      treating a patient with dementia. Ethical and legal issues will also be discussed
      as they must be considered when providing holistic care.

PMID- 21727833
TI  - Alzheimer's or the normal course of ageing?

PMID- 21727835
TI  - Communicating news of a patient's death to relatives.
AB  - Breaking the news of the death of a patient to their relatives is one of the most
      difficult and dreaded aspects of nursing. While it is not an aspect of the job
      that nurses relish, it is key that nursing staff have full understanding of their
      role during this time to allow them to communicate this difficult news in a
      sensitive manner. This article will examine the role of the nurse in
      communicating the news of a patient's death to their next of kin and relatives.
      Staff education and training to deal with the bereaved will be assessed, as will
      the nurse's perceptions of their role. The impact of the nurse's presence on the
      bereaved will be looked at, and finally the role of the nurse in bereavement
      follow up will conclude this article.

PMID- 21727834
TI  - Rheumatology helpline: challenges in the biologic therapy era.
AB  - For rheumatology patients, telephone helplines can provide rapid access to
      management, advice, information and support. In many cases, the provision of a
      telephone helpline reflects an attempt to make care more flexible and patient
      based. The 'direct' mode advice delivery can only be informally compared with the
      traditional route of patient access to advice, which often travelled a complex
      route via overworked medical secretaries or receptionists toward the final
      destination of medical staff, sometimes engaged in other activities. This article
      will discuss the challenges facing the rheumatology helpline and how these can be
      tackled.

PMID- 21727836
TI  - Spirituality in nursing: a systematic review of the literature from 2006-10.
AB  - Spirituality in nursing care has been discussed for many years in the nursing
      press. There has been no literature review that explores only UK literature, and
      this article updates a literature review carried out in 2006 (Ross, 2006). aIM:
      The review was designed to investigate the current nursing evidence underpinning
      the concept of spirituality and its application. METHOD: A systematic review of
      the literature was undertaken and a thematic analysis performed following a
      search for literature using defined dates, databases and search terms. RESULTS:
      Four major themes emerged from the literature: concept clarification; spiritual
      care-giving; religion and spirituality; and nurse education. CONCLUSION:
      Definitions of spiritual care vary, and the concept of spirituality in nursing is
      still under development. However, until a common language of spirituality is
      developed, models of spiritual care developed through research involving mainly
      nursing staff will be difficult for nurses to apply.

PMID- 21727837
TI  - Perceptions of a clinical psychology support group for spinal injury.
AB  - BACKGROUND: A service evaluation was performed exploring nurses' perceptions of a
      clinical psychology facilitated peer support group in a spinal injury
      rehabilitation setting. AIMS: To determine whether staff found the meetings
      useful while, more broadly, to highlight the need to support and supervise
      nursing staff in psychological care appropriately. METHOD: A questionnaire was
      developed and distributed to the 30 members of staff who worked on the ward.
      Seventeen questionnaires were returned (57%). Data was analysed using thematic
      analysis. RESULTS: The meetings were viewed as a place to discuss issues, and a
      safe protected space to share stresses. Staff felt the meetings aided team
      cohesion and helped them share ideas and draw up clinical strategies. Meetings
      aided stress management and confidence building. Staff considered the meetings to
      increase their psychological awareness and understanding. CONCLUSION: Staff
      involved in the acute care and rehabilitation of spinal injured patients are
      consistently exposed to highly demanding and stressful clinical environments.
      Support meetings where staff can discuss patient and ward issues are invaluable.
      Other clinical nursing areas would benefit from similar support systems.

PMID- 21727838
TI  - Writing for publication made easy for nurses: an evaluation.
AB  - AIM: The purpose of the project was to encourage and support nurses to write
      papers for publication in a peer-reviewed journal. BACKGROUND: Writing for
      publication is an important nursing role as it is a means of communicating
      knowledge, skills and experiences to improve patient outcomes. Despite the
      importance, nurses have limited confidence and experiences with publishing
      nursing developments. METHODS: A comprehensive development programme was designed
      to provide direction and leadership on how to write for publication. Fifty
      participants attended the programme and it was led and supported by two
      experienced facilitators. RESULTS: A multi-method approach to evaluation was
      undertaken including attendance, an evaluation questionnaire, a focus group and a
      review of writing outcomes. By one year from commencement of programme, 25% had
      submitted a paper for peer review publication. The programme created and
      sustained motivation to write and participants valued the taught focused sessions
      as well as the unstructured group discussion sessions. CONCLUSION: The writing
      for publication programme for nurses, midwives and allied health professionals
      was successful.

PMID- 21727839
TI  - The state of health care and adult social care in England.

PMID- 21727840
TI  - Are young people welcome in the health service?

PMID- 21727841
TI  - Supporting self and others: from staff nurse to nurse consultant. Part 4:
      mentoring.
AB  - This series of articles explores various ways of supporting staff who work in the
      fast-moving and ever-changing health service. In previous articles, John Fowler
      an experienced nursing lecturer, author and consultant, examined the importance
      of developing a supportive working culture, learning from experience and the role
      of preceptorship. This article examines how the principles of mentoring, as
      practiced in the business world, can be applied to nursing.

PMID- 21727842
TI  - 'Missing links' in venous leg ulcer management.

PMID- 21727843
TI  - Effect of nutrition on wound healing in older people: a case study.
AB  - Wound healing requires an increase in the energy intake of the patient due to an
      increase in metabolic demand. Nutrition plays a vital role in the wound healing
      process, as various nutrients have specific functions related to wound healing.
      Adequate nutrition is required to maintain healthy skin integrity, and
      malnourished patients often experience delayed wound healing as a result of this.
      Additionally, older people may have difficulty meeting their nutritional
      requirements owing to a diminished dietary intake. Effective management of
      malnourished patients with wounds depends on accurate early diagnosis and
      treatment. This short case study critically analyses the care that was provided
      in one NHS trust to a malnourished older patient with a wound. Recommendations
      for improving practice include early identification of malnourished patients,
      early referral for dietetic assessment and tissue viability intervention, and
      education for health professionals.

PMID- 21727844
TI  - Interim advice on silver dressings in paediatric wound and skin care.

PMID- 21727845
TI  - The assessment and management of skin tears in care homes.
AB  - This article discusses a project conducted in Worcestershire nursing homes to
      review current practices in the management of skin tears and the subsequent
      development and implementation of guidelines resulting in a standardised client
      care package. An initial audit in five care homes was followed by an in-depth
      audit in 52 homes over a 12-week period. This led to the development of resources
      and the 'STAR box' to assist with implementation of timely and appropriate care
      delivery.

PMID- 21727846
TI  - Debridement--is it time to revisit clinical practice?
AB  - Debridement is the removal of non-viable tissue from a wound bed. It is an
      essential procedure in order to achieve wound healing and symptom control. The
      clinical presentation of non-viable tissue varies in content, appearance, depth
      and level of hydration. There may be a risk of systemic infection if non-viable
      tissue is not removed in a timely fashion. There are various methods of
      debridement each with its own advantages and limitations. The competence of the
      practitioner undertaking the debridement is crucial and is a key consideration
      along with availability of the necessary equipment and the provision of the
      optimal environment. Client choice and involvement are vital to the debridement
      process. There should be no hierarchy of debridement methods and the chosen
      method should achieve timely optimal pain-free removal of non-viable tissue.
      There is a need to question the current situation in which the specialist nurse
      is highly skilled in the debridement process while the generalist nurse
      potentially carries a higher caseload of patients who require this procedure.

PMID- 21727847
TI  - Now is the time for tissue viability.
AB  - Tissue viability nurses (TVNs) have always been interested in pressure ulcers.
      Many found our way into the specialism because of this interest and passion. We
      have always believed most of them could be prevented and our desire, our goal has
      been to prevent all avoidable pressure ulcers.

PMID- 21727848
TI  - Evaluation of patient outcomes: pressure ulcer prevention mattresses.
AB  - This article reports the findings of a small evaluation audit which compares the
      Dyna-Form Mercury Advance Mattress to that of the Softform Premier Active
      Mattress (a foam mattress with dynamic underlay). A small group of patients with
      similar co-morbidities who were an emergency admission were recruited to an
      evaluation audit. Their median age and Waterlow score indicated that these
      patients were at high risk of pressure ulcer development. All patients were given
      the same nursing care on the two mattresses and all were moved, handled and
      repositioned 2-4 hourly. Of the patients nursed on the Dyna-Form Mercury Advance
      mattress, three did not develop pressure ulcers. The two who already had pressure
      ulcers when they were recruited appeared to have healed within four days. Of the
      patients nursed on the Softform Premier Active mattress, three patients did not
      develop ulcers and two did. Although the sample size was small, the comprehensive
      assessment gave interesting results, particularly on the Dyna-Form Mercury
      Advance. A larger study may be of benefit to demonstrate efficacy of these
      products further.

PMID- 21727849
TI  - Abusing the privelege to care--shame on us.

PMID- 21727850
TI  - Remembering Florence Nightingale.

PMID- 21727851
TI  - The lived experiences of newly qualified children's nurses.
AB  - AIM: This paper reports a study that explored the lived experiences of newly
      qualified registered children's nurses (RCN) in their transition from
      postgraduate student nurse to staff nurse. RESEARCH QUESTION: What are the
      experiences of newly qualified RCNs in their transition from postgraduate student
      nurse to staff nurse? METHODS: A qualitative phenomenological approach was chosen
      for the study and six newly qualified RCNs were interviewed. Data analysis was
      based on the work of Coliazzi (1978) who devised a seven-step approach to assist
      the analysis within phenomenological inquiry. RESULTS: Findings indicate that
      support is the most important aspect of the transition experience for these
      nurses. Mentorship and preceptorship programmes facilitate support during the
      transition period and previous experience prescribes the amount of support
      required by the newly qualified RCN. CONCLUSION: In highlighting the experiences
      of newly qualified RCNs in their transition from postgraduate student nurse to
      staff nurse, this study raises awareness among children's nurses, children's
      nurse educators and children's nursing managers about this unique group of
      nurses.

PMID- 21727852
TI  - Introducing evidence into nursing practice: using the IOWA model.
AB  - Evidence-based practice has gained increasing popularity in all healthcare
      settings. Nurses are urged to use up-to-date research evidence to ensure better
      patient outcomes and inform decisions, actions and interactions with patients, to
      deliver the best possible care. Within the practice setting, there is an
      increasing challenge to provide clearly measurable care of the highest quality,
      which is evidence-based. In order for nurses to operate from an evidence-based
      perspective, they need to be aware of how to introduce, develop and evaluate
      evidence-based practice. This article presents how evidence may be introduced
      into practice using the Iowa model, offering practical advice and explanation of
      the issues concerning nurses in practice.

PMID- 21727853
TI  - The nature of leadership style in nursing management.
AB  - The purpose of this study was to explore the nature of leadership styles used by
      nurse managers, and describe staff nurses' perceptions of leadership styles.
      Effective leadership among nurse managers has been associated with staff nurse
      job satisfaction and retention. Twenty staff nurses from two hospitals in Ghana
      responded to tape-recorded interview questions. Four themes emerged from
      inductive analysis of the data. Findings suggest that nurse managers employed
      intimidation and minimal consultation to control their employees. The study
      further indicated that nurse managers were perceived as 'figure-heads', who are
      weak and inarticulate at the level of policy planning and implementation. It was
      therefore concluded that staff nurses in the study site hospitals lack
      confidence, trust and satisfaction with the current style of leadership. Staff
      nurses preferred a more proactive, articulate and independent nursing leadership
      at the top level. It is recommended that effective leadership training be
      instituted for prospective nurse managers before appointments are made into
      management and administrative positions.

PMID- 21727854
TI  - Compression bandaging: types and skills used in practical application.
AB  - This article discusses long- and short-stretch compression bandages and the
      theory underpinning their practical application. The Laplace equation is outlined
      to estimate sub-bandage pressures. Challenges associated with applying
      therapeutic levels of compression include bandage tension, number of layers, limb
      circumference and bandage width. Multi-layer bandaging is important for the
      management of chronic oedema. As poor bandaging techniques can lead to tissue
      damage, pain, oedema and necrosis, practitioners should be skilled in their
      application. Through collaboration between specialists and generalists and
      ongoing practice development, patient outcomes can be improved.

PMID- 21727855
TI  - Cleaning the hospital environment--a focus on Difficil-S.
AB  - Providing a healthcare environment that is aesthetically clean and
      microbiologically safe, remains a key component to combating the spread of
      healthcare-associated infections (HCAIs). Patients now demand to be cared for in
      an environment that is conducive to healing without the fear of contracting an
      HCAI. The number of 'superbugs' are escalating, posing a challenge when cleaning
      and disinfecting surfaces. There has been little regard paid to the products used
      within the clinical setting and how these may affect the quality of cleaning and
      disinfection. The variety of patient equipment now present within wards and the
      pace staff are exposed to requires a simplified cleaning regime. One such way
      forward may be the use of Difficil-S(r), which is a sporicidal and cleaning agent
      providing an opportunity to simplify the cleaning process within the clinical
      setting.

PMID- 21727856
TI  - International patient safety experience: sharing the lessons.
AB  - John Tingle discusses two recent patient safety reports from Canada and Australia
      that contain important lessons for health professionals worldwide.

PMID- 21727858
TI  - Supporting self and others: from staff nurse to nurse consultant. Part 3:
      preceptorship.
AB  - This series of articles explores different ways of supporting staff who work in
      the fast-moving and ever-changing health service. In the first two articles, John
      Fowler, an experienced nursing lecturer, author and consultant, examined the
      importance of developing a supportive working culture and how learning from
      experience can result in both positive and negative consequences. This article
      examines the importance of preceptorship for all staff taking on new roles.

PMID- 21727857
TI  - Demonstrating and measuring achievement.
AB  - Professor Alan Glasper discusses the Government's listening exercise and
      consultation into the modernization of the NHS, launched at the beginning of
      April 2011.

PMID- 21727860
TI  - Poetry in nursing.

PMID- 21727859
TI  - The creation of modern-day nursing.
AB  - The publication of a lecture in the BJN 100years ago highlighted the fact that as
      science was advancing at that time so medical men have had to be drawn from a
      higher intellectual and social stratum than ever before, and nurses 'as their
      collaborators, equally so!'. This was the opinion of a French Physician called
      Dr. Rist in a key lecture he gave at the Sorbonne in Paris.

PMID- 21727874
TI  - Industry, teach us about research!
AB  - At the time of writing, it is barely a week since the European Wound Management
      Association conference in Brussels. For me, one of the highlights of these events
      is the opportunity to meet so many readers and get feedback on the journal. It
      was also great to see EWMA and other wound-care associations, industry
      representatives and practitioners all working together to achieve the shared goal
      of disseminating information on best practice. A perfect example of tripartite
      working.

PMID- 21727875
TI  - Minor amputation in patients with diabetes mellitus and severe foot ulcers
      achieves good outcomes.
AB  - OBJECTIVE: To analyse the outcome of minor amputations (through, or distal to,
      the ankle joint) in patients with diabetes. METHOD: All diabetic patients in a
      defined population undergoing one or more minor amputation between 1982 and 2006
      were investigated according to a standardised protocol and were followed until
      final outcome (healing or death). A total of 410 consecutive amputations in 309
      patients with a median age of 73 (32-93) years were identified. RESULTS: In 94%
      of amputations, deep infection (39%) and/or gangrene (55%) was present. Severe
      peripheral vascular disease or critical limb ischaemia was present in 61% of
      amputations. 261/410 (64%) of the amputations healed at a level below the ankle
      joint; 69/410 (17%) healed after a re-amputation above the ankle joint; in 76/410
      of amputations (19%), the patient died before healing could occur. In surviving
      patients, 79% of the amputations healed below the ankle. Median healing time for
      amputations that healed below the ankle was 26 (2-250) weeks; 21% of amputations
      required a re-amputation above the ankle. None of the analysed parameters
      excluded the possibility of healing below the ankle. CONCLUSION: In this
      population-based survey, the goal of avoiding major amputation was achieved in
      almost two thirds of minor amputations, but at the price of long healing times.
      In almost all amputations, the patient had deep infection and/or gangrene. In
      spite of this, 64% of all amputations, and 79% of amputations in surviving
      patients, healed at a level below the ankle. This indicates that minor
      amputations in these patients are worthwhile. DECLARATION OF INTEREST: None.

PMID- 21727876
TI  - The use of acellular dermal regeneration template for recalcitrant pilonidal
      disease.
AB  - Numerous techniques have been described for the treatment of pilonidal disease,
      yet there remains no consensus on the optimal management of recurrent pilonidal
      disease. Pilonidal wounds often lack the structural integrity to heal over and
      Integra provides a scaffold for the regrowth of an autogenous dermis from the
      patient's own fibroblasts and collagen. Postoperative negative pressure wound
      therapy (NPWT) may speed vascularisation of Integra, re-epithelialisation, and
      wound closure. This case report concerns two patients with chronic pilonidal
      sinuses who underwent wide excision and placement of Integra with postoperative
      NPWT. Postoperatively, the patients were assessed for complications and
      recurrence. Both patients went on to heal and did not require further surgical
      treatment after a median follow-up of 29 months. Integra may help prevent pocket
      or cyst formation during the closure process and provides a neodermis, allowing
      for full re-epithelialisation. More research and a longer follow-up are needed to
      evaluate the role of Integra and NPWT in recurrent pilonidal disease.

PMID- 21727877
TI  - Clinical evaluation of a PHMB-impregnated biocellulose dressing on paediatric
      lacerations.
AB  - OBJECTIVE: To evaluate the clinical benefits, primarily tolerability and
      reduction in pain levels, associated with the use of a PHMB-impregnated
      biosynthetic cellulose dressing (Suprasorb X + PHMB) on paediatric heel
      lacerations. METHOD: These lacerations were caused when children, who were being
      transported on their parents' bicycles, got their heels trapped in the wheel
      spokes. Where these injuries just comprised skin contusion and laceration,
      treatment had previously comprised cleansing followed by application of
      conventional dressings and moist wound healing dressings. However, the high
      incidence of infection necessitated regular dressing changes, which caused
      parents and children stress and anxiety. This clinical evaluation assessed the
      benefits of a new treatment protocol, where the PHMB-impregnated biocellulose
      dressing was applied and left in situ until epithelialisation occurred. A cork
      splint was used for 3 days to prevent pes equinus and to let the ankle joint
      rest. Change in wound size (cm2), incidence of local infection, wound bed
      characteristics and pain levels (measured on a 0-10 paediatric pain scale) were
      assessed at 3-day intervals during the 14-day treatment period. Satisfaction with
      the dressing was also evaluated. RESULTS: Twenty children (mean age 5.6 years (+/
      1.33) were recruited into the study and included in the analysis. The mean
      baseline wound area was 8.60cm2 (+/- 6.57). The mean time to complete wound
      closure was 12.95 days (+/- 7.69) with a mean total of 4.70 visits (+/- 1.56).
      The mean VAS pain score was 9.55 (+/- 0.69), compared with 0.15 (+/- 0.37) on day
      14 (p<0.003). At the second visit (after 3 days) 17 of the 20 children were
      reported to be free of pain. No cases of local infection were noted. CONCLUSION:
      The dressing was found to be child and parent friendly. The evaluation also
      showed that it was well tolerated and achieved good healing outcome. It has now
      been incorporated into the clinic's treatment protocol for these wounds. CONFLICT
      OF INTEREST: None. The authors have no relevant financial interest in this
      article. All authors were involved in the critical revision of the manuscript for
      important intellectual content.

PMID- 21727878
TI  - Silver debate continue.

PMID- 21727879
TI  - Vitamins and cutaneous wound healing.
AB  - BACKGROUND: Vitamins have long been thought to modulate the various stages of
      wound healing through a variety of proposed mechanisms. Our goal was to
      investigate relevant studies examining the role of different vitamins in wound
      healing. METHODS: MEDLINE, Cochrane Database of Systematic Reviews, and Google
      Scholar were searched for basic science and clinical studies examining the role
      of vitamins as adjuncts in wound healing. RESULTS: Mechanisms of action for each
      of the vitamins are reviewed. It was suggested by many of the studies that the
      major vitamins A, C, E, D, K, and B have demonstrated utility as adjuncts in
      wound care in basic science and clinical trials. CONCLUSION: There is a vast
      amount of literature on the effect of vitamins on wound healing at the basic
      science level. Further understanding and controlled trials will help better
      understand how to utilize vitamins in wound care. DECLARATION OF INTEREST: None.

PMID- 21727880
TI  - Green foam, black foam or gauze for NWPT: effects on granulation tissue
      formation.
AB  - OBJECTIVE: To compare the effects of green foam with black foam and gauze during
      negative pressure wound therapy (NPWT), with regard to wound bed appearance and
      granulation tissue formation, and monitoring of wound exudate. METHOD: Wounds on
      the backs of eight pigs underwent 72 hours of NPWT plus either green polyurethane
      foam with an open pore structure, black polyurethane foam with an open pore
      structure or saline-moistened AMD gauze. Sections of biopsies from the wound bed,
      including the overlying dressing, were examined histologically with regard to
      microdeformation of the wound bed and granulation tissue formation. The force
      required to remove the wound fillers was measured. RESULTS: Wound exudate and
      bleeding could be easily seen when using gauze and green foam, but were not
      visible under the black foam. Such visibility facilitates monitoring of the wound
      status. No difference was found in the quantity or characteristics of the
      granulation tissue formed under the green foam or black foam. Both green foam and
      black foam resulted in more pronounced granulation tissue formation than gauze
      under negative pressure. There was also more leucocyte infiltration and tissue
      disorganisation under green foam and black foam than under gauze. All three wound
      fillers created microdeformation within the wound bed surface. Similar forces
      were required to remove green foam and black foam (5.0 +/- 0.6 N for green foam
      and 4.0 +/- 0.4 N for black foam), while less force was needed for gauze (2.1 +/-
      0.2 N). This may be a result of tissue ingrowth into the foam (357 +/- 12um for
      green foam and 362 +/- 14um for black foam), but not into gauze (0um), as shown
      by examination of biopsy sections from the wound bed. CONCLUSION: Green foam and
      black foam have similar biological effects on the wound bed. Bleeding and exudate
      can be more easily monitored when using green foam or gauze. Differences in the
      wound bed tissue morphology when using foam or gauze plus NPWT support clinical
      observations that granulation tissue under foam is thick but fragile, whereas
      that under foam is thinner but denser. CONFLICT OF INTEREST: The study was
      supported by Molnlycke Health Care AB.

PMID- 21727881
TI  - Are postoperative dressings necessary?
AB  - OBJECTIVE: To determine whether or not the routine use of postoperative dressings
      prevents surgical site infection and wound dehiscence. MATERIAL AND METHODS:
      Patients with clean or clean-contaminated (e.g. hernia, orchidectomy
      cystolithotomy, ureterolithotomy, appendectomy) sutured surgical wounds were
      randomised into two groups: those who did not receive postoperative dressings
      (the study group) and those who did (the control group). Variables like adequate
      haemostasis, sterile techniques, obliteration of all wound cavities, and
      approximation of divided structures were not controlled for. Wounds were assessed
      after 6 and 24 hours, and on the third and fifth postoperative days for clinical
      signs of infection and dehiscence. RESULTS: A total of 123 patients with 124
      clean surgical wounds were recruited into the study. The mean age and ratio of
      men and women in each group were comparable. There was no significant difference
      in the rate of wound complications between the two groups: 4.76% for the study
      group and 4.92% for control. CONCLUSION: Based on these preliminary data,
      surgical wounds left open do not have an increased incidence of surgical site
      infection and wound dehiscence, compared with similar types of wounds dressed
      postoperatively. In a large teaching hospital, the extrapolated cost savings of
      dressing materials alone can be significant. Larger studies are needed to confirm
      these results. CONFLICT OF INTEREST: None.

PMID- 21727882
TI  - Reaching out: doing 'good' in the name of palliative care.

PMID- 21727884
TI  - Nursing students' concerns about end of life in California, Norway, and Sweden.
AB  - AIM: To investigate concerns about dying for newly admitted nursing students from
      California, Norway, and Sweden. METHOD: A total of 389 undergraduate nursing
      students who had just started their nursing programme participated. Data was
      collected with a questionnaire that included two instruments-the Concerns about
      Dying instrument and the Sense of Coherence instrument-and background questions.
      The data was analysed using statistical and content analysis. RESULTS: There were
      statistically significant differences between the three groups of students in
      terms of their age, their experience in health care, whether they had previously
      attended a dying patient, the age at which they first encountered the death of a
      loved one, and their concerns about dying. Two main categories emerged from the
      analysis of the open questions: 'attending to dying and grieving persons' and
      'thinking about one's own death'. CONCLUSION: The study provides important
      insights into the concerns that newly admitted students bring to the nursing
      programme.

PMID- 21727883
TI  - Nurses' participation in the end-of-life process in two paediatric intensive care
      units in Brazil.
AB  - The aim of this study was to evaluate the medical and nursing care provided to
      children in the last 24 hours of life in two Brazilian paediatric intensive care
      units and analyse the nurses' participation in the decision-making process for
      life support limitation (LSL). The study was based on an analysis of the
      patients' medical charts, looking at the medical and nursing care provided in the
      last 24 hours of life during a 6-month period in the two units, and on semi
      structured interviews with 20 nurses to evaluate their participation in LSL
      decisions. The children were classified into two groups: those who were to
      receive full cardiopulmonary resuscitation (CPR) and a non-CPR group. A total of
      34 deaths occurred during the study period. Of these, 17 (50%) were children that
      had been in the non-CPR group; there were only 10 recorded LSL plans in their
      medical charts. In the interviews, only 30% of the nurses mentioned active
      participation in LSL decisions. In conclusion, the paediatric intensive care
      nurses in these two Brazilian units did not participate much in LSL decisions,
      and the care offered in the last hours of life to children with terminal and
      irreversible illness was not primarily directed toward comfort and alleviating
      suffering.

PMID- 21727885
TI  - Anticipating emotion: a qualitative study of advance care planning in the
      community setting.
AB  - Advance care planning at the end of life is high on the political agenda across
      the UK. The aim is to deliver patient-centred care for all patients, whenever
      possible in their preferred place of care. It is widely acknowledged that
      discussions about the end of life are sensitive and often difficult for health
      professionals, particularly those in the community setting. The aim of this
      qualitative study was to determine the factors that assist or hinder the primary
      care health professionals having these discussions. The sample included one GP
      and one district nurse (DN) from each of three GP practices. Semi-structured
      interviews were conducted with the participants, and the data was analysed using
      a thematic approach. The findings clearly depict two of the challenges faced by
      the GPs and DNs in the community: emotional labour, and balancing patients' and
      families' expectations about care provision in the community with the limited
      resources available. This study contributes to the knowledge base of advance care
      planning by providing insight into the experiences of the GPs and DNs who care
      for patients at the end of life. Further research is required to more fully
      understand the emotional impact on the health professionals having these
      sensitive discussions.

PMID- 21727886
TI  - An exploration of the concerns of patients with inoperable lung cancer.
AB  - Appraisal of the literature suggests that patients with lung cancer report more
      unmet supportive care needs and greater psychological distress than patients with
      other cancers. This study aimed to explore the concerns of patients with
      inoperable lung cancer and to interpret those concerns to inform specialist
      palliative care nursing practice. A descriptive qualitative study was undertaken
      using semi-structured interviews with six participants on a single site. Three
      main themes were identified: steadfastly living life, family support and
      separation, and trust in professionals. The latter is crucial for enabling
      patients to express their concerns, which in turn allows support to be directed
      appropriately and from a patient-centred perspective.

PMID- 21727887
TI  - A nation's pain: the current state of palliative care provision in Ukraine.

PMID- 21727888
TI  - What are patients' priorities when facing the end of life? A critical review.
AB  - This critical review aimed to investigate what patients' priorities are when
      facing the end of life, in order to gain further understanding of this issue.
      Academic databases were searched using key terms, and through a method of
      elimination and deduction using specific inclusion/exclusion criteria, suitable
      research studies were found. These articles were then assessed for their quality,
      and specific data was extracted from the final selection using appropriate
      information-gathering tools. In these final four articles the methodological
      processes used to explore terminally ill patients' needs were generally
      appropriate, although there was a lack of reflexivity (researcher reflection on
      the experience). Useful narrative themes were produced from all four papers for
      further discussion. The patients had similar priorities across all four articles,
      which were related to understanding and accepting their changing health status,
      the need to hold on to some normality in life, the need to feel supported by
      friends and family and to know they will be taken care of after the death, and
      the need to have good and trusting relationships with health professionals.

PMID- 21727889
TI  - UK telehealth initiatives in palliative care: a review.
AB  - This review paper explores the use of telehealth in relation to palliative care
      in the UK. Information technology (IT) developments are being harnessed
      throughout society, and there is growing interest in the ways in which they can
      be used to meet and support patients' health needs in the community. The aim of
      the literature review was to scope the information available from published and
      unpublished research, with particular reference to older people. The evidence
      suggests that, despite the challenges, there are numerous examples of good
      practice in relation to telehealth, palliative and end-of-life care, and older
      people. Developments in technology that have increased the capacity to improve
      care, through reaching greater numbers of people of all age groups, mean that
      telehealth has much to offer people living with and dying from advanced illness.
      However, some of the evaluative evidence is limited and further rigour is needed
      when evaluating future telehealth innovations.

PMID- 21727892
TI  - Lianqiaoxinoside B, a novel caffeoyl phenylethanoid glycoside from Forsythia
      suspensa.
AB  - Chemical investigation of the 70% ethanol extract of the unripe fruits of
      Forsythia suspensa resulted in the isolation of a novel caffeoyl phenylethanoid
      glycoside, lianqiaoxinoside B, together with the known compound forsythoside H.
      The new compound was elucidated to be 1'',2''-[beta-(3,4,-dihydroxylphenyl)
      alpha,beta-dioxoethanol]-3''-O-caffeoyl-O-alpha-rhamnopyranosyl-(1->6)-O-beta
      glucopyranoside by extensive spectroscopic and chemical studies. Lianqiaoxinoside
      B and forsythoside H showed strong antioxidant and antimicrobial activities in
      vitro by the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonate (ABTS) radical
      scavenging assay and plate method. This study can be further extended to exploit
      for the possible application of caffeoyl phenylethanoid glycosides as the
      alternative antioxidants and antimicrobial agents of natural origin.

PMID- 21727893
TI  - Synthesis and anticancer activity of some new s-glycosyl and s-alkyl 1,2,4
      triazinone derivatives.
AB  - A series of S-glycosyl and S-alkyl derivatives of 4-amino-3-mercapto-6-(2-(2
      thienyl)vinyl)-1,2,4-triazin-5(4H)-one (1) were synthesized using different halo
      compounds such as preacetylated sugar bromide, 4-bromobutylacetate, 2
      acetoxyethoxy-methyl bromide, 3-chloropropanol, 1,3-dichloro-2-propanol,
      epichlorohydrin, allyl bromide, propargyl bromide, phthalic and succinic acids in
      POCl3. The structures of the synthesized compounds have been deduced from their
      elemental analysis and spectral (IR, 1H-NMR, and 13C-NMR) data. Some of the
      synthesized compounds were screened as anticancer agents. Significant anticancer
      activities were observed in vitro for some members of the series, and compounds 4
      Amino-3-(3-hydroxypropylthio)-6-(2-(2-thienyl)vinyl)-1,2,4-triazin-5(4H)-one (12)
      and 3-(4-Oxo-3-(2-(2-thienyl)vinyl)-4H-[1,3,4]thiadiazolo-[2,3-c][1,2,4]tr-iazin
      7-yl)propanoic acid (18) are active cytotoxic agents against different cancer
      cell lines.

PMID- 21727894
TI  - Conserved properties of human and bovine prion strains on transmission to guinea
      pigs.
AB  - The first transmissions of human prion diseases to rodents used guinea pigs (Gps,
      Cavia porcellus). Later, transgenic mice expressing human or chimeric human/mouse
      PrP replaced Gps, but the small size of the mouse limits some investigations. To
      investigate the fidelity of strain-specific prion transmission to Gps, we
      inoculated 'type 1' and 'type 2' prion strains into Gps, and we measured the
      incubation times and determined the strain-specified size of the unglycosylated,
      protease-resistant (r) PrP(Sc) fragment. Prions passaged once in Gps from cases
      of sporadic (s) Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler
      Scheinker (GSS) disease caused by the P102L mutation were used, as well as human
      prions from a variant (v) CJD case, bovine prions from bovine spongiform
      encephalopathy (BSE) and mouse-passaged scrapie prions. Variant CJD and BSE
      prions transmitted to all the inoculated Gps with incubation times of 367 +/- 4
      and 436 +/- 28 days, respectively. On second passage in Gps, vCJD and BSE prions
      caused disease in 287 +/- 4 and 310 +/- 4 days, whereas sCJD and GSS prions
      transmitted in 237 +/- 4 and 279 +/- 19 days, respectively. Although hamster
      Sc237 prions transmitted to two of three Gps after 574 and 792 days, mouse
      passaged RML and 301V prion strains, the latter derived from BSE prions, failed
      to transmit disease to Gps. Those Gps inoculated with vCJD or BSE prions
      exhibited 'type 2' unglycosylated, rPrP(Sc) (19 kDa), whereas those receiving
      sCJD or GSS prions displayed 'type 1' prions (21 kDa), as determined by western
      blotting. Such strain-specific properties were maintained in Gps as well as mice
      expressing a chimeric human/mouse transgene. Gps may prove particularly useful in
      further studies of novel human prions such as those causing vCJD.

PMID- 21727895
TI  - Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.
AB  - The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in
      Wnt-driven proliferative compartments. We find that conditional deletion of both
      genes in the mouse gut impairs Wnt target gene expression and results in the
      rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass
      spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt
      receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can
      bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals
      initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but
      abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re
      expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal
      crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway
      activation. Lgr5 homologues are facultative Wnt receptor components that mediate
      Wnt signal enhancement by soluble R-spondin proteins. These results will guide
      future studies towards the application of R-spondins for regenerative purposes of
      tissues expressing Lgr5 homologues.

PMID- 21727896
TI  - Aging and functional brain networks.
AB  - Aging is associated with changes in human brain anatomy and function and
      cognitive decline. Recent studies suggest the aging decline of major functional
      connectivity hubs in the 'default-mode' network (DMN). Aging effects on other
      networks, however, are largely unknown. We hypothesized that aging would be
      associated with a decline of short- and long-range functional connectivity
      density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting
      state data sets corresponding to 913 healthy subjects from a public magnetic
      resonance imaging database using functional connectivity density mapping (FCDM),
      a voxelwise and data-driven approach, together with parallel computing. Aging was
      associated with pronounced long-range FCD decreases in DMN and dorsal attention
      network (DAN) and with increases in somatosensory and subcortical networks. Aging
      effects in these networks were stronger for long-range than for short-range FCD
      and were also detected at the level of the main functional hubs. Females had
      higher short- and long-range FCD in DMN and lower FCD in the somatosensory
      network than males, but the gender by age interaction effects were not
      significant for any of the networks or hubs. These findings suggest that long
      range connections may be more vulnerable to aging effects than short-range
      connections and that, in addition to the DMN, the DAN is also sensitive to aging
      effects, which could underlie the deterioration of attention processes that
      occurs with aging.

PMID- 21727897
TI  - Air pollution impairs cognition, provokes depressive-like behaviors and alters
      hippocampal cytokine expression and morphology.
AB  - Particulate matter air pollution is a pervasive global risk factor implicated in
      the genesis of pulmonary and cardiovascular disease. Although the effects of
      prolonged exposure to air pollution are well characterized with respect to
      pulmonary and cardiovascular function, comparatively little is known about the
      impact of particulate matter on affective and cognitive processes. The central
      nervous system may be adversely affected by activation of reactive oxygen species
      and pro-inflammatory pathways that accompany particulate matter pollution. Thus,
      we investigated whether long-term exposure to ambient fine airborne particulate
      matter (<2.5 MUm (PM(2.5))) affects cognition, affective responses, hippocampal
      inflammatory cytokines and neuronal morphology. Male mice were exposed to either
      PM(2.5) or filtered air (FA) for 10 months. PM(2.5) mice displayed more
      depressive-like responses and impairments in spatial learning and memory as
      compared with mice exposed to FA. Hippocampal pro-inflammatory cytokine
      expression was elevated among PM(2.5) mice. Apical dendritic spine density and
      dendritic branching were decreased in the hippocampal CA1 and CA3 regions,
      respectively, of PM(2.5) mice. Taken together, these data suggest that long-term
      exposure to particulate air pollution levels typical of exposure in major cities
      around the globe can alter affective responses and impair cognition.

PMID- 21727898
TI  - Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA
      signature in peripheral blood mononuclear cells.
AB  - MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and
      are important for coordinating nervous system development and neuronal function
      in the mature brain. We have recently identified schizophrenia-associated
      alteration of cortical miRNA biogenesis and expression in post-mortem brain
      tissue with implications for the dysregulation of schizophrenia candidate genes.
      Although these changes were observed in the central nervous system, it is
      plausible that schizophrenia-associated miRNA expression signatures may also be
      detected in non-neural tissue. To explore this possibility, we investigated the
      miRNA expression profile of peripheral blood mononuclear cells (PBMCs) from 112
      patients with schizophrenia and 76 non-psychiatric controls. miRNA expression
      analysis of total RNA conducted using commercial miRNA arrays revealed that 33
      miRNAs were significantly downregulated after correction for multiple testing
      with a false discovery rate (FDR) of 0%, which increased to 83 when we considered
      miRNA with an FDR<5%. Seven miRNAs altered in microarray analysis of
      schizophrenia were also confirmed to be downregulated by quantitative real-time
      reverse transcription-polymerase chain reaction. A large subgroup consisting of
      17 downregulated miRNAs is transcribed from a single imprinted locus at the
      maternally expressed DLK1-DIO3 region on chromosome 14q32. This pattern of
      differentially expressed miRNA in PBMCs may be indicative of significant
      underlying genetic or epigenetic alteration associated with schizophrenia.

PMID- 21727899
TI  - Targeting the BH3-interacting domain death agonist to develop mechanistically
      unique antidepressants.
AB  - The BH3-interacting domain death agonist (Bid) is a pro-apoptotic member of the B
      cell lymphoma-2 (Bcl-2) protein family. Previous studies have shown that stress
      reduces levels of Bcl-2 in brain regions implicated in the pathophysiology of
      mood disorders, whereas antidepressants and mood stabilizers increase Bcl-2
      levels. The Bcl-2 protein family has an essential role in cellular resilience as
      well as synaptic and neuronal plasticity and may influence mood and affective
      behaviors. This study inhibited Bid in mice using two pharmacological antagonists
      (BI-11A7 and BI-2A7); the selective serotonin reuptake inhibitor citalopram was
      used as a positive control. These agents were studied in several well-known
      rodent models of depression-the forced swim test (FST), the tail suspension test
      (TST), and the learned helplessness (LH) paradigm-as well as in the female urine
      sniffing test (FUST), a measure of sex-related reward-seeking behavior.
      Citalopram and BI-11A7 both significantly reduced immobility time in the FST and
      TST and attenuated escape latencies in mice that underwent the LH paradigm. In
      the FUST, both agents significantly improved duration of female urine sniffing in
      mice that had developed helplessness. LH induction increased the activation of
      apoptosis-inducing factor (AIF), a caspase-independent cell death constituent
      activated by Bid, and mitochondrial AIF expression was attenuated by chronic BI
      11A7 infusion. Taken together, the results suggest that functional perturbation
      of apoptotic proteins such as Bid and, alternatively, enhancement of Bcl-2
      function, is a putative strategy for developing novel therapeutics for mood
      disorders.

PMID- 21727901
TI  - Clinical and radiographic evaluation of the shoulder of spinal cord injured
      patients undergoing rehabilitation program.
AB  - STUDY DESIGN: Clinical and radiographic evaluation of the shoulders of
      tetraplegic and paraplegic patients who attend rehabilitation program.
      OBJECTIVES: The objective of this study is to establish the usefulness of
      radiography as a trial exam for shoulder pain in spinal cord injured patients.
      SETTING: Hospital das Clinicas-UNICAMP. Campinas, Sao Paulo, Brazil. METHODS:
      Thirty-two shoulders of 16 patients were evaluated by clinical exam and
      radiography. Patients were divided into two groups: paraplegic and tetraplegic. A
      control group of 16 normal volunteer subjects was selected. RESULTS: Shoulder
      pain was reported in 88.89% of tetraplegic and 42.85% of paraplegic. The time of
      injury ranged from 1.5-22 years (mean 7.88 years); patients had a mean age of
      34.68 years (range, 21-57 years). The acromioclavicular joint (ACJ) space ranged
      from 0.03-0.7 cm on the right side and 0.15-0.7 cm on the left side, with a mean
      of 0.37 and 0.41 cm, respectively. No correlation was found between shoulder pain
      and gender, age or time since injury. There was a trend to correlation between
      shoulder pain and type of injury with tetraplegic having a tendency to pain
      symptoms. On average, tetraplegic had smaller ACJ. CONCLUSIONS: The small number
      of patients in this study did not allow us to confirm the hypothesis that X-ray
      finding may indicate risk for shoulder pain in spinal cord injury patients. A
      work with a greater number of subjects could demonstrate association between
      shoulder pain and the reduced acromioclavicular distance, making plain
      radiography a trial exam for spinal cord-injured patients.

PMID- 21727900
TI  - Bone marrow stem cell mobilization in stroke: a 'bonehead' may be good after all!
AB  - Mobilizing bone cells to the head, astutely referred to as 'bonehead' therapeutic
      approach, represents a major discipline of regenerative medicine. The last decade
      has witnessed mounting evidence supporting the capacity of bone marrow (BM)
      derived cells to mobilize from BM to peripheral blood (PB), eventually finding
      their way to the injured brain. This homing action is exemplified in BM stem cell
      mobilization following ischemic brain injury. Here, I review accumulating
      laboratory studies implicating the role of therapeutic mobilization of
      transplanted BM stem cells for brain plasticity and remodeling in stroke.

PMID- 21727902
TI  - Relative vulnerability of various spinal tracts in C3-4 cervical spondylotic
      myelopathy: multi-modal spinal cord evoked potentials.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the progression of
      spinal tract lesions in cervical spondylotic myelopathy (CSM) at C3-4
      intervertebral level using spinal cord-evoked potensials (SCEPs). SETTING: This
      study was conducted at the Department of Orthopaedic Surgery, Yamaguchi
      University Graduate School of Medicine, Japan. METHODS: A total of 30 patients
      with CSM were investigated in this study. In all patients, only the C3-4
      intervertebral level was symptomatic, as shown by examination of SCEPs. SCEPs
      were recorded following median nerve stimulation (MN-SCEPs), transcranial
      electric stimulation (TES-SCEPs) and spinal cord stimulation (spinal-SCEPs).
      RESULTS: The incidence of abnormalities varied in the order of MN-SCEPs (100%),
      TES-SCEPs (90%) and spinal-SCEPs (67%). Patients were grouped into three types
      according to SCEPs: transverse (all SCEPs abnormal), post-erolateral
      (abnormalities in the MN-SCEPs and TES-SCEPs) and upper limbs sensory (abnormal
      only for MN-SCEPs). In all, 20 of the 30 patients (67%) were the transverse type,
      7 (23%) the post-erolateral type and 3 (10%) the upper limbs sensory type.
      CONCLUSION: The present study showed the lateral part of the posterior funiculus
      mediating upper limb sensory function was more vulnerable than the lateral
      corticospinal tract, which is consistent with numbness tending to appear at an
      early stage of mild CSM.

PMID- 21727903
TI  - Epigenomics: Reprogramming in transition.

PMID- 21727904
TI  - Control of macrophage lineage populations by CSF-1 receptor and GM-CSF in
      homeostasis and inflammation.
AB  - There is recent interest in the role of monocyte/macrophage subpopulations in
      pathology. How the hemopoietic growth factors, macrophage-colony stimulating
      factor (M-CSF or CSF-1) and granulocyte macrophage (GM)-CSF, regulate their in
      vivo development and function is unclear. A comparison is made here on the effect
      of CSF-1 receptor (CSF-1R) and GM-CSF blockade/depletion on such subpopulations,
      both in the steady state and during inflammation. In the steady state,
      administration of neutralizing anti-CSF-1R monoclonal antibody (mAb) rapidly
      (within 3-4 days) lowered, specifically, the number of the more mature Ly6C(lo)
      peripheral blood murine monocyte population and resident peritoneal macrophages;
      it also reduced the accumulation of murine exudate (Ly6C(lo)) macrophages in two
      peritonitis models and alveolar macrophages in lung inflammation, consistent with
      a non-redundant role for CSF-1 (or interleukin-34) in certain inflammatory
      reactions. A neutralizing mAb to GM-CSF also reduced inflammatory macrophage
      numbers during antigen-induced peritonitis and lung inflammation. In GM-CSF gene
      deficient mice, a detailed kinetic analysis of monocyte/macrophage and neutrophil
      dynamics in antigen-induced peritonitis suggested that GM-CSF was acting, in
      part, systemically to maintain the inflammatory reaction. A model is proposed in
      which CSF-1R signaling controls the development of the macrophage lineage at a
      relatively late stage under steady state conditions and during certain
      inflammatory reactions, whereas in inflammation, GM-CSF can be required to
      maintain the response by contributing to the prolonged extravasation of immature
      monocytes and neutrophils. A correlation has been observed between macrophage
      numbers and the severity of certain inflammatory conditions, and it could be that
      CSF-1 and GM-CSF contribute to the control of these numbers in the ways proposed.

PMID- 21727905
TI  - Blood lipid levels and prostate cancer risk; a cohort study.
AB  - It has been hypothesized that blood lipid levels might be associated with
      prostate cancer risk. The aim of the present study was to evaluate the
      association between serum total cholesterol, high-density lipoprotein (HDL)
      cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and
      prostate cancer risk in a cohort study among 2842 Dutch men. By the end of follow
      up, 64 incident cases of prostate cancer were identified. Serum total
      cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were evaluated as
      potential risk factors for prostate cancer using multivariable Cox proportional
      hazards regression models. These analyses were restricted to men who never used
      cholesterol-lowering drugs (2118 men, 43 cases). Higher total and higher LDL
      cholesterol were significantly associated with an increased risk of prostate
      cancer (hazards ratios (HR) and 95% confidence interval (CI) per mmol l(-1) were
      1.39 (95% CI 1.03-1.88) and 1.42 (95% CI 1.00-2.02), respectively). Similar
      results were observed for aggressive prostate cancer, whereas for non-aggressive
      prostate cancer a significant association with HDL cholesterol was found (HR
      4.28, 95% CI 1.17-15.67). The results of this study suggest that blood lipid
      levels may influence risk of prostate cancer. However, the exact roles of
      different cholesterol fractions on prostate cancer aggressiveness should be
      further evaluated.

PMID- 21727906
TI  - Predictive value of digital rectal examination for prostate cancer detection is
      modified by obesity.
AB  - The American Cancer Society's updated screening guidelines for prostate cancer
      (CaP) render digital rectal examination (DRE) optional. We investigated the
      impact of DRE on CaP detection among obese men. Data from 2794 men undergoing
      initial prostate biopsy at three centers were analyzed to assess CaP risk
      attributed to abnormal DRE across body mass index (BMI) categories. Predictive
      accuracies of a combination of PSA, age, race, center and biopsy year including
      or excluding DRE findings were compared by areas under the receiver-operating
      characteristics curves. In all cohorts, obese men were less likely to have
      abnormal DREs diagnosed than non-obese men. As BMI category increased, abnormal
      DREs became stronger predictors for overall CaP in individual (P-trends <= 0.05)
      and combined (P-trend<0.001) cohorts, and for high-grade CaP in the Italian (P
      trend=0.03) and combined (P-trend=0.03) cohorts. DRE inclusion improved the
      predictive accuracy for overall and high-grade CaP detection among all obese men
      (P <= 0.032) but not normal-weight men (P >= 0.198). DRE inclusion also near
      significantly improved overall CaP detection in obese men with PSA<4 ng ml(-1)
      (P=0.081). In conclusion, the predictive value of DRE is dependent on obesity and
      is significantly higher among obese men than normal-weight men.

PMID- 21727907
TI  - Lithium, an anti-psychotic drug, greatly enhances the generation of induced
      pluripotent stem cells.
AB  - Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by
      defined factors. The low efficiency of reprogramming and genomic integration of
      oncogenes and viral vectors limited the potential application of iPSCs. Here we
      report that Lithium (Li), a drug used to treat mood disorders, greatly enhances
      iPSC generation from both mouse embryonic fibroblast and human umbilical vein
      endothelial cells. Li facilitates iPSC generation with one (Oct4) or two factors
      (OS or OK). The effect of Li on promoting reprogramming only partially depends on
      its major target GSK3beta. Unlike other GSK3beta inhibitors, Li not only
      increases the expression of Nanog, but also enhances the transcriptional activity
      of Nanog. We also found that Li exerts its effect by promoting epigenetic
      modifications via downregulation of LSD1, a H3K4-specific histone demethylase.
      Knocking down LSD1 partially mimics Li's effect in enhancing reprogramming. Our
      results not only provide a straightforward method to improve the iPSC generation
      efficiency, but also identified a histone demethylase as a critical modulator for
      somatic cell reprogramming.

PMID- 21727909
TI  - DNA methylation: a new twist in the tail.

PMID- 21727908
TI  - Identification and expansion of cancer stem cells in tumor tissues and peripheral
      blood derived from gastric adenocarcinoma patients.
AB  - Gastric cancer is the fourth most common cancer worldwide, with a high rate of
      death and low 5-year survival rate. To date, there is a lack of efficient
      therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem
      cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and
      resistance to anticancer therapies. Thus, therapies that target gastric CSCs are
      attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been
      described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC
      patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and
      peripheral blood of patients carried CD44 and CD54 surface markers, generated
      tumors that highly resemble the original human tumors when injected into
      immunodeficient mice, differentiated into gastric epithelial cells in vitro, and
      self-renewed in vivo and in vitro. Our findings suggest that effective
      therapeutic protocols must target GCSCs. The capture of GCSCs from the
      circulation of GAC patients also shows great potential for identification of a
      critical cell population potentially responsible for tumor metastasis, and
      provides an effective protocol for early diagnosis and longitudinal monitoring of
      gastric cancer.

PMID- 21727910
TI  - Pharmacotherapy: SSRIs and congenital abnormalities.

PMID- 21727911
TI  - Autoimmunity: thyroid autoantibodies and pregnancy risk.

PMID- 21727912
TI  - Development: disorders of sex development-the tip of the iceberg?

PMID- 21727913
TI  - Bone: osteoporosis therapy--time to consider renal function.

PMID- 21727915
TI  - Venous thromboembolism: outpatient care is noninferior to inpatient care for low
      risk patients with acute pulmonary embolism.

PMID- 21727914
TI  - Familial forms of diabetes insipidus: clinical and molecular characteristics.
AB  - Over the past two decades, the genetic and molecular basis of familial forms of
      diabetes insipidus has been elucidated. Diabetes insipidus is a clinical syndrome
      characterized by the excretion of abnormally large volumes of diluted urine
      (polyuria) and increased fluid intake (polydipsia). The most common type of
      diabetes insipidus is caused by lack of the antidiuretic hormone arginine
      vasopressin (vasopressin), which is produced in the hypothalamus and secreted by
      the neurohypophysis. This type of diabetes insipidus is referred to here as
      neurohypophyseal diabetes insipidus. The syndrome can also result from resistance
      to the antidiuretic effects of vasopressin on the kidney, either at the level of
      the vasopressin 2 receptor or the aquaporin 2 water channel (which mediates the
      re-absorption of water from urine), and is referred to as renal or nephrogenic
      diabetes insipidus. Differentiation between these two types of diabetes insipidus
      and primary polydipsia can be difficult owing to the existence of partial as well
      as complete forms of vasopressin deficiency or resistance. Seven different
      familial forms of diabetes insipidus are known to exist. The clinical
      presentation, genetic basis and cellular mechanisms responsible for them vary
      considerably. This information has led to improved methods of differential
      diagnosis and could provide the basis of new forms of therapy.

PMID- 21727916
TI  - Coronary artery disease: how should the STICH trial results affect clinical
      practice?
AB  - The STICH trial showed that CABG surgery does not necessarily improve
      cardiovascular outcomes in patients with coronary artery disease and left
      ventricular dysfunction who are receiving optimal medical therapy. However,
      surgical revascularization should still be considered if the coronary artery
      disease is severe and viable myocardium can be identified.

PMID- 21727921
TI  - Short-term international migration trends in England and Wales from 2004 to 2009.
AB  - Short-term migration estimates for England and Wales are the latest addition to
      the Office for National Statistics (ONS) migration statistics. This article
      discusses definitions of short-term migration and the methodology that is used to
      produce the estimates. Some of the estimates and the changes in the estimates
      over time are then discussed. The article includes previously unpublished short
      term migration statistics and therefore helps to give a more complete picture of
      the size and characteristics of short-term international migration for England
      and Wales than has previously been possible. ONS have identified a clear user
      requirement for short-term migration estimates at local authority (LA) level.
      Consequently, attention is also paid to the progress that has been made and
      future work that is planned to distribute England and Wales short-term migration
      estimates to LA level.

PMID- 21727917
TI  - Arterial thrombus formation in cardiovascular disease.
AB  - The pathogenesis of arterial thrombosis is complex and dynamic. Unlike venous
      thrombi, arterial thrombi typically form under conditions of high blood flow and
      are mainly composed of platelet aggregates, giving them the appearance of 'white
      clots'. Strong evidence suggests that arterial thrombi originate as a consequence
      of an injured atherosclerotic plaque, and that their formation involves the
      release of prothrombotic material (such as tissue factor), platelet aggregation,
      and platelet adhesion to the vascular wall. The initially labile platelet plaque
      is then stabilized by insoluble fibrin produced upon activation of the
      coagulation cascade. Inherited genetic factors (gene polymorphisms) and acquired
      predisposing conditions (such as the concentration and activity of clotting
      factors) can influence both the composition and the size of an arterial thrombus.
      Further research is needed to elucidate the functions of blood coagulation
      proteins and cellular elements that are critical to the pathogenesis of arterial
      thrombosis. This Review explains mechanisms of pathological arterial thrombus
      formation and discusses genetic and acquired risk factors of atherothrombosis.

PMID- 21727918
TI  - Dietary factors associated with hypertension.
AB  - Hypertension is one of the major risk factors for cardiovascular disease, with an
      impact on global health. Multiple studies have suggested that various dietary
      factors are associated with blood pressure (BP) and hypertension. The purpose of
      this Review is to provide up-to-date knowledge on the impact of dietary factors
      on BP and hypertension, to compare types and recommended intakes of dietary
      factors in hypertension management and prevention guidelines from different
      countries and organizations, and to outline global population-based healthy-diet
      strategies for hypertension control. Of the 27 dietary factors we evaluated on
      the basis of specified review criteria, 17 have been proposed to have protective
      effects against hypertension, six were proposed to be risk factors for
      hypertension, and the association between BP and the remaining factors was
      considered inconclusive. Excessive sodium intake is a causal risk factor for
      hypertension, whereas a diet rich in fruit, vegetables, and low-fat dairy
      products, and low in sodium and saturated fat has been recommended to prevent and
      reduce hypertension on the basis of strong evidence. Notable differences exist in
      the recommended types and intakes of dietary factors among available hypertension
      management and prevention guidelines. Available evidence supports the vigorous
      implementation of dietary strategies against hypertension through population
      based, national action plans.

PMID- 21727922
TI  - Estimating fertility rates using the ONS Longitudinal Study--what difference does
      the inclusion of non-continually resident members make?
AB  - Among datasets available for fertility research in England and Wales, the Office
      for National Statistics (ONS) Longitudinal Study (LS) is unique in its
      construction and scale. The large number of individuals who are part of the study
      means that it is an important dataset for estimating fertility trends in England
      and Wales by age and parity. This article uses the LS to estimate age-specific
      fertility rates (ASFRs) for England and Wales between 1991 and 2001. This
      necessitates great care to ensure that the exposure to risk of birth for female
      LS members is fully understood. To achieve this, two forms of residential history
      are defined - consistent cases where the residential information for the LS
      member is potentially complete for the whole decade and inconsistent cases where
      there is certainly some form of incompleteness in the residence information. By
      considering 'all consistent cases', that is both the continuously resident plus
      those who are not continuously resident but appear to have a complete residential
      history, we obtain ASFRs which are slightly lower than official statistics
      figures, but closer to these official figures than ASFRs produced when
      restricting the sample to LS members who remain continuously resident between
      1991 and 2001. The fertility of those consistent cases who are not continuously
      resident is substantially higher than the rates of continuously resident cases.

PMID- 21727923
TI  - Who reports address changes through the healthcare system? The characteristics of
      laggers and non-reporters using the Northern Ireland Longitudinal Study.
AB  - Address information from health service professionals is already important for
      the delivery of health care and population monitoring and screening. It is also
      important for statistical purposes such as the estimation of migration and small
      area populations and its importance could increase as the decade progresses and
      alternatives are sought to the traditional census. Because of this, it is
      important to understand more about the accuracy of address information provided
      through the health care system.This article considers the characteristics of
      'laggers' - those who delay in reporting address changes - and 'non-reporters' -
      those who on occasion fail to report their addresses.The article finds that, as
      might be expected, laggers and non-reporters tend to be male and resident in
      urban and deprived areas. However, less expectedly, older people tend to be
      laggers, as are owner occupiers, those who are not ill, those who have some
      educational qualifications, and those who are self-employed. Some non-reporters
      are also more likely to be employed in professional jobs and to be unmarried (for
      example single, remarried and divorced). This suggests that poor address
      information is not just a problem associated with the socially deprived and the
      young but also with some more affluent groups such as those not experiencing
      limiting long-term illness. The article concludes by arguing that the checking of
      patients' address information should be collected under the Quality and Outcomes
      Framework (QOF) as a performance indicator.

PMID- 21727924
TI  - Cardiovascular disease: CKD increases the risk of atrial fibrillation.

PMID- 21727927
TI  - Acute kidney injury: Is it possible to predict recovery from acute kidney injury?

PMID- 21727925
TI  - What are the anticoagulation options for intermittent hemodialysis?
AB  - Prevention of clotting in the extracorporeal circuit was one of the major hurdles
      that had to be overcome to enable the expansion of routine outpatient
      hemodialysis to free-standing satellite centers and the home. Unfractionated
      heparin, the anticoagulant of choice for many years, is now being replaced by low
      molecular-weight heparins (LMWHs) in an expanding number of countries. This trend
      is attributable to the ease and convenience of the administration of LMWHs
      coupled with their reliability and predictability of dosing. However, the choice
      of which LMWH to use depends on the duration and frequency of the dialysis
      sessions. For patients who are allergic to heparin or have heparin-induced
      thrombocytopenia, alternative anticoagulants--the direct thrombin inhibitors and
      heparinoids--are now available. These agents either have short half-lives (and
      therefore need to be delivered by infusions), or prolonged half-lives, which
      allows simple bolus administration, but increases the risk of drug accumulation,
      overdosage and hemorrhage. In patients at risk of bleeding, regional
      anticoagulants enable anticoagulation to be limited to the extracorporeal
      circuit. Prostanoids and nafamostat mesilate are expensive regional
      anticoagulants, and citrate infusions add complexity to the procedure. A citrate
      based dialyzate has now been introduced that might enable heparin-free dialysis
      or reduce systemic anticoagulant requirements.

PMID- 21727929
TI  - Immunotherapy: Novel approach for universal adoptive cell transfer therapy with
      improved outcome.

PMID- 21727928
TI  - New era for drug discovery and development in renal disease.
AB  - Drug discovery and development is a lengthy and expensive process. Testing new
      agents in humans at an early stage could reduce the time and costs involved in
      identifying drugs that are likely to succeed in clinical studies. New guidance
      has outlined the concept of exploratory clinical trials, which provide important
      information on a drug's distribution as well as its physiological and
      pharmacological effects in humans. This strategy reduces the need for preclinical
      testing by limiting the dose and duration of exposure to a new drug in humans to
      below those required by the traditional testing of investigational new drugs.
      Exploratory, first-in-man studies should provide insights into human physiology
      and pharmacology, identify therapeutic targets relevant to disease and increase
      our knowledge of a drug's characteristics. Implementation of a new drug also
      requires the development of useful biomarkers of disease and of the drug's
      efficacy, as well as sensitive molecular imaging techniques. In this Review, we
      outline the benefits of exploratory clinical trials, especially in academia, and
      provide an overview of the experimental tools necessary for rational drug
      discovery and development.

PMID- 21727930
TI  - Chemotherapy: Metastatic pancreatic cancer--is FOLFIRINOX the new standard?

PMID- 21727931
TI  - Immunotherapy: Tumor-infiltrating T cells--ready for prime time in melanoma?

PMID- 21727932
TI  - Prevention: MAPping out breast cancer chemoprevention.

PMID- 21727933
TI  - Genetics of monogenic autoinflammatory diseases: past successes, future
      challenges.
AB  - The term autoinflammation was initially coined to distinguish disorders
      characterized by recurrent episodes of inflammation in the absence of high-titer
      autoantibodies and antigen-specific T cells from the more common autoimmune
      diseases. Although this concept originally applied to monogenic hereditary
      recurrent fevers, it has expanded over time to include polygenic (complex)
      autoinflammatory diseases. Understanding of the pathogenesis of autoinflammatory
      diseases has grown rapidly in the past decade owing to advances in genome
      research and technology. Genome-wide linkage analysis, positional cloning,
      homozygosity mapping and candidate gene screening have led to the identification
      of mutations in 12 genes that are associated with monogenic diseases. Genome-wide
      association studies have begun to elucidate the molecular basis of complex
      autoinflammatory diseases. The discovery of disease-causing genetic variants has
      defined autoinflammation as disorder within the innate immune system, implicating
      IL-1 as a master cytokine, and has led to a breakthrough in therapy, with IL-1
      inhibitors producing rapid and sustained amelioration of symptoms. Despite major
      advances, however, a substantial number of patients have no mutations in the
      known autoinflammatory genes. The challenge now is to find the undiscovered
      genes, considering that most cases are sporadic or occur within small families.
      New approaches and tools such as next-generation sequencing are discussed.

PMID- 21727934
TI  - Pediatric rheumatology: Improving the assessment of children with JIA.

PMID- 21727936
TI  - Surgical approaches to the treatment of obesity.
AB  - Bariatric surgery, through its efficacy and improved safety, is emerging as an
      important and broadly available treatment for people with severe and complex
      obesity that has not responded adequately to other therapy. Established
      procedures, such as Roux-en-Y gastric bypass and adjustable gastric banding,
      account for more than 80% of bariatric surgical procedures globally. Sleeve
      gastrectomy has emerged as a stand-alone procedure. Truly malabsoptive
      procedures, such as biliopancreatic diversion and its duodenal switch variant,
      have a diminishing role as primary procedures, but remain an option for patients
      who do not respond adequately to less disruptive procedures. The procedures vary
      considerably in their postoperative morbidity and mortality; pattern and extent
      of weight loss; nature and severity of long-term complications; and nutritional
      requirements and risks. There is no perfect procedure--an informed risk and
      benefit assessment should be made by each patient. Gastroenterologists also need
      to be familiar with the risks and benefits of current and emerging procedures as
      they are likely to be increasingly involved in the integrated care of these
      patients.

PMID- 21727937
TI  - Pancreas: Postoperative pancreatic fistula: use of enteral nutrition.

PMID- 21727938
TI  - Virtual imaging laboratories for marker discovery in neurodegenerative diseases.
AB  - The unprecedented growth, availability and accessibility of imaging data from
      people with neurodegenerative conditions has led to the development of
      computational infrastructures, which offer scientists access to large image
      databases and e-Science services such as sophisticated image analysis algorithm
      pipelines and powerful computational resources, as well as three-dimensional
      visualization and statistical tools. Scientific e-infrastructures have been and
      are being developed in Europe and North America that offer a suite of services
      for computational neuroscientists. The convergence of these initiatives
      represents a worldwide infrastructure that will constitute a global virtual
      imaging laboratory. This will provide computational neuroscientists with a
      virtual space that is accessible through an ordinary web browser, where image
      data sets and related clinical variables, algorithm pipelines, computational
      resources, and statistical and visualization tools will be transparently
      accessible to users irrespective of their physical location. Such an experimental
      environment will be instrumental to the success of ambitious scientific
      initiatives with high societal impact, such as the prevention of Alzheimer
      disease. In this article, we provide an overview of the currently available e
      infrastructures and consider how computational neuroscience in neurodegenerative
      disease might evolve in the future.

PMID- 21727939
TI  - Multiple sclerosis: MS treatment adherence--how to keep patients on medication?

PMID- 21727940
TI  - Integration and analysis of genome-scale data from gliomas.
AB  - Primary brain tumors are a leading cause of cancer-related mortality among young
      adults and children. The most common primary malignant brain tumor, glioma,
      carries a median survival of only 14 months. Two major multi-institutional
      programs, the Glioma Molecular Diagnostic Initiative and The Cancer Genome Atlas,
      have pursued a comprehensive genomic characterization of a large number of
      clinical glioma samples using a variety of technologies to measure gene
      expression, chromosomal copy number alterations, somatic and germline mutations,
      DNA methylation, microRNA, and proteomic changes. Classification of gliomas on
      the basis of gene expression has revealed six major subtypes and provided
      insights into the underlying biology of each subtype. Integration of genome-wide
      data from different technologies has been used to identify many potential protein
      targets in this disease, while increasing the reliability and biological
      interpretability of results. Mapping genomic changes onto both known and inferred
      cellular networks represents the next level of analysis, and has yielded proteins
      with key roles in tumorigenesis. Ultimately, the information gained from these
      approaches will be used to create customized therapeutic regimens for each
      patient based on the unique genomic signature of the individual tumor. In this
      Review, we describe efforts to characterize gliomas using genomic data, and
      consider how insights gained from these analyses promise to increase
      understanding of the biological underpinnings of the disease and lead the way to
      new therapeutic strategies.

PMID- 21727941
TI  - The placebo effect in overactive bladder syndrome.
AB  - Overactive bladder syndrome (OAB) is a condition that involves urinary urgency
      and affected individuals are usually treated with behavioral therapy and
      antimuscarinic agents as first-line therapies. Existing evidence from clinical
      trial data suggests that a positive placebo effect occurs in patients receiving
      treatment for OAB. In our systematic Review of placebo-controlled, randomized
      trials in OAB, we show statistically significant improvements in three patient
      reported outcomes-incontinence episodes per day, micturition episodes per day and
      mean micturition volume from baseline-after placebo in randomized studies for
      OAB. The findings could highlight the brain's role in the pathophysiology of OAB
      or the role of additional bladder training conducted as part of OAB clinical
      trials. More research is needed to determine the underlying mechanisms of the
      placebo effect in OAB.

PMID- 21727943
TI  - Isostructural copper-zinc mixed metal complexes for single source deposition of
      Cu-ZnO composite thin films.
AB  - The mixed metal complex [Zn(TFA)(3)(MU-OH)Cu(3)(dmae)(3)Br].THF (1) and its
      isostructural analogues ([Zn(TFA)(3)(MU-OH)Cu(3)(dmae)(3)Cl].THF (2) and
      [Zn(TFA)(3)(MU-OH)Cu(3)(dmae)(3)Cl/Br].THF (3)) have been prepared by a simple
      metal ligand assembly method and were characterized by their melting points,
      elemental analysis, IR spectroscopy, thermogravimetry and single crystal X-ray
      structures. The compounds are distinguished only by the nature of the halide ions
      and are made up of the same [Zn(TFA)(3)(MU-OH)Cu(3)(dmae)(3)X].THF molecular
      building block with Cu(3)ZnO(4) cubane moieties as the central core in which the
      four metal ions and four oxygen atoms are joined together in alternate positions
      of the cuboid. All the complexes crystallize with similar packing and
      crystallographically related symmetry settings, distinguished mainly by the
      degree of disorder within the complexes and the ordering of the complexes in the
      structures. The triclinic cell of (1) emulates the monoclinic cell of (2) and is
      pseudomerohedrally twinned by a symmetry operation of the monoclinic cell. The
      molecules in (2) are 1:1 disordered around a crystallographic mirror plane. The
      structure of the mixed halogen compound (3) in turn is a superstructure of the
      less symmetric structures of (1) and (2) formed by ordering of the complexes
      along the longest axis of (3). Aerosol-assisted chemical vapour deposition
      (AACVD) experiments showed that they are promising precursors to deposit thin
      films of crystalline Cu/ZnO composites. The surface morphology, microstructure,
      chemical composition and crystallinity of the resulting Cu/ZnO composite thin
      films were analysed by scanning electron microscopy (SEM), X-ray diffraction
      (XRD) and energy dispersive X-ray analysis (EDAX), which suggest that the films
      are thin, crystalline, uniform, smooth and tightly adherent to the substrates
      with average crystallite sizes in a range between 40.2 and 80.0 nm. Particle
      sizes, shapes and film morphology were investigated as a function of precursor
      and decomposition temperature.

PMID- 21727942
TI  - Prognostic factors for upper urinary tract urothelial carcinoma.
AB  - Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, which means
      there are little evidence-based data available to guide clinical decision-making.
      Although diagnosis and treatment of UTUC have improved significantly over the
      last 5 years, accurate risk stratification remains a challenge owing to the
      difficulty of clinical staging. A number of potential prognostic factors have
      been identified, encompassing clinical characteristics, pathological factors and
      molecular markers. Tumor stage and lymph node status are the most important
      predictors of survival in patients with UTUC. Preoperative evaluation for
      hydronephrosis can identify patients at risk of non-organ-confined disease. In
      the subgroup of patients with stage >=pT2 disease, a longer interval between
      diagnosis and radical nephroureterectomy is associated with a higher risk of
      disease recurrence and cancer-specific mortality. Extensive tumor necrosis,
      sessile tumor architecture and lymphovascular invasion are independent predictors
      of clinical outcomes for patients with UTUC treated with radical
      nephroureterectomy. The incorporation of such prognosticators into clinical
      prediction models might help to guide decision-making with regard to timing of
      surveillance, type of treatment, performance of lymphadenectomy, and
      consideration of neoadjuvant or adjuvant systemic therapies.

PMID- 21727953
TI  - Extraction of silver(I) from aqueous solutions in the absence and presence of
      copper(II) with a methimazole-based ionic liquid.
AB  - The ionic liquid (IL) 2-butylthiolonium bis(trifluoromethanesulfonyl)amide,
      [mimSBu][NTf(2)], facilitates the efficient extraction of silver(I) from aqueous
      media via interaction with both the cation and anion components of the IL.
      Studies with a conventional aqueous-IL two phase system as well as
      microextraction of silver(I) by a thick IL film adhered to an electrode monitored
      in situ by cyclic voltammetry, established that [mimSBu][NTf(2)] can extract
      electroactive silver(I) ions from an aqueous solution. The pH of the aqueous
      phase decreases upon addition of [mimSBu](+), which is attributed to partial
      release of the hydrogen attached to the N(3) nitrogen atom of the imidazolium
      ring. The presence of silver(I) further increase the acidity of the aqueous phase
      as a consequence of coordination with the IL cation component. Voltammetric and
      (1)H and (13)C NMR techniques have been used to establish the nature of the
      silver(I) complexes extracted, and show that the form of interaction with the IL
      differs from that outlined previously for the extraction of copper(II). Insights
      on the competition established when silver(I) is extracted in the presence of
      copper(II) are provided. Finally, it is noted that metallic silver can be
      directly electrodeposited at the electrode surface after extraction of silver(I)
      into [mimSBu][NTf(2)] and that back extraction of silver(I) into aqueous media is
      achieved by addition of an acidic aqueous solution.

PMID- 21727954
TI  - Transfer hydrogenation of unfunctionalised alkenes using N-heterocyclic carbene
      ruthenium catalyst precursors.
AB  - Transfer hydrogenation of unfunctionalised and aliphatic alkenes in iPrOH/KOH is
      efficiently catalysed by an olefin-tethered N-heterocyclic carbene ruthenium
      complex, which also catalyses double bond migration as a competitive and
      considerably faster process.

PMID- 21727955
TI  - Comparison of electrode materials for the detection of rapid hydrogen peroxide
      fluctuations using background-subtracted fast scan cyclic voltammetry.
AB  - Hydrogen peroxide (H(2)O(2)) is a critically important signaling molecule.
      Endogenous H(2)O(2) mediates diverse physiological processes both intra- and
      intercellularly; and enzymatically generated H(2)O(2) is a widely used reporter
      molecule at biosensors that rely on enzymes to detect non-electroactive species.
      However, the development and application of electroanalytical methods for the
      direct detection of this molecule has been challenging because the electron
      transfer kinetics for the irreversible oxidation of H(2)O(2) are slow. We
      comparatively characterize the electrochemical oxidation of H(2)O(2) on bare and
      Nafion((r))-coated platinum and carbon-fiber microdisc electrodes using fast-scan
      cyclic voltammetry (FSCV). Using a waveform ranging from +0.2 to +1.3 V at 400 V
      s(-1), the electrocatalytic properties of the platinum surface were not readily
      apparent, and the carbon-fiber microelectrode demonstrated greater sensitivity
      and selectivity toward H(2)O(2). Nafion((r))-coating further enhanced detection
      on carbon electrodes. These results confirm that platinum electrodes, with or
      without Nafion((r)), will not work acceptably with this approach, and confirm the
      value of carbon-fiber microelectrodes relative to more traditionally used
      platinum electrodes in the direct detection of rapid H(2)O(2) fluctuations using
      FSCV.

PMID- 21727956
TI  - Synthesis of epoxybenzo[d]isothiazole 1,1-dioxides via a reductive-Heck,
      metathesis-sequestration protocol.
AB  - An atom-economical purification protocol, using solution phase processing via
      ring-opening metathesis polymerization (ROMP) has been developed for the
      synthesis of tricyclic sultams. This chromatography-free method allows for
      convenient isolation of reductive-Heck products and reclamation of excess
      starting material via sequestration involving metathesis catalysts and a catalyst
      armed Si-surface.

PMID- 21727957
TI  - A label-free, direct and noncompetitive FRET immunoassay for ochratoxin A based
      on intrinsic fluorescence of an antigen and antibody complex.
AB  - A label-free, direct and noncompetitive homogeneous immunoassay, in which
      ochratoxin A (OTA) coupled with the anti-OTA antibody participates in
      fluorescence resonance energy transfer (FRET), was developed for the detection of
      OTA with great specificity and a detection limit of 1 ng mL(-1).

PMID- 21727958
TI  - Dual functions of a novel low-gap polymer for near infra-red photovoltaics and
      light-emitting diodes.
AB  - We have synthesised and characterised a new low-gap conjugated polymer, with a
      broad absorption profile. In blends with a C(70) derivative we demonstrate power
      conversion efficiencies of 0.76%. We show electroluminescence from the polymer
      peaking at 956 nm, and quantum efficiency of 0.02% in a blend.

PMID- 21727959
TI  - One-pot synthesis of hollow/porous Mn-based nanoparticles via a controlled ion
      transfer process.
AB  - A general one-pot protocol is reported to prepare hollow or porous manganese (Mn)
      oxide, phosphate, sulfide nanoparticles (NPs) via a controlled ion transfer
      process.

PMID- 21727960
TI  - Synthesis of an insulated molecular wire by click polymerization.
AB  - We developed a new method for the synthesis of an organic-soluble insulated
      molecular wire (IMW) with permethylated cyclodextrin (PMCD); this method involves
      click polymerization of linked [2]rotaxane containing azide and alkynyl groups at
      both ends of a pi-conjugated guest.

PMID- 21727961
TI  - The continuous-flow cycloaddition of azomethine ylides to carbon nanotubes.
AB  - This communication demonstrates a straightforward continuous-flow method for
      efficient exohedral functionalisation of carbon nanotubes which affords soluble
      samples in a much shorter time over conventional batch processing.

PMID- 21727962
TI  - Copper-catalyzed N-arylation of amines with part-per-million catalyst loadings
      under air at room temperature.
AB  - An efficient copper-catalyzed method for N-arylation of amines has been developed
      with part-per-million catalyst loadings at room temperature under air. Reactions
      of substituted (E)-1-(2-halophenyl)alkanone oximes with aliphatic amines or
      aromatic amines provided the N-arylation products in good to excellent yields.

PMID- 21727963
TI  - Correlation between composition and hydrogen storage behaviors of the Li2NH-MgNH
      combination system.
AB  - Hydrogen storage performances of a Li(2)NH-xMgNH combination system (x = 0, 0.5,
      1 and 2) are investigated for the first time. It is found that the hydrogenated
      samples with MgNH exhibit a significant reduction in the dehydrogenation
      temperatures. Mechanistic investigations reveal that there is a strong dependence
      of the hydrogen storage reaction process on the molar ratio between MgNH and
      Li(2)NH. As a consequence, tuning of thermodynamics is achieved for hydrogen
      storage in the Li(2)NH-xMgNH system by changing the reaction routes, which is
      ascertained to be the primary reason for the reduction in the operating
      temperature for hydrogen desorption. Specifically, it is found that under 105 atm
      hydrogen (140-280  degrees C) 5.6 wt% hydrogen is reversibly stored in the
      Li(2)NH-0.5MgNH combination system, which is greater than in the well
      investigated Mg(NH(2))(2)-2LiH system.

PMID- 21727964
TI  - Amido-based potassium-alkaline earth metallates--synthesis and structures of
      heterobimetallic complexes of heavy s-block elements.
AB  - The metathesis reaction of potassium N-isopropylanilide with alkaline earth metal
      diiodides of calcium, strontium and barium in a molar ratio of 4:1 yields the
      corresponding alkaline earth metalates of the type [(THF)(n)K(MU-NPhiPr)(2)Ae(MU
      NPhiPr)(2)K(THF)(n)] (1: Ae = Ca, n = 2). Stabilization and crystallization of
      such derivatives succeeds after exchange of the THF ligands by multidentate amino
      bases such as tetramethylethylenediamine (TMEDA) or pentamethyldiethylenetriamine
      (PMDETA). The influence of the size and hardness of the alkaline earth metal
      center on the molecular structures is studied with [(L)K(MU-NPhiPr)(2)Ae(MU
      NPhiPr)(2)K(L)] (2: Ae = Ca, L = TMEDA; 3: Ae = Sr, L = TMEDA; 4: Ae = Sr, L =
      PMDETA; and 5: Ae = Ba, L = PMDETA). The molecular structures are dominated by
      (attractive and repulsive) electrostatic and steric factors leading to a
      shortening of the non-bonding AeK distances from calcium to barium.

PMID- 21727965
TI  - Dynamics of steroid estrogen daily concentrations in hospital effluent and
      connected waste water treatment plant.
AB  - Hospital effluent and connected waste water treatment plant (WWTP) influent and
      effluent were sampled daily to determine the levels and inter-day variations of
      three naturally occurring steroid estrogens: estrone, 17beta-estradiol, estriol,
      and synthetic 17alpha-ethinylestradiol. After solid phase extraction,
      interferences were removed with a silica gel clean-up step and the samples
      analysed using gas chromatography with mass selective detection (GC-MSD). The
      determined inter-day concentrations in hospital effluent were between 8.6 to 31.3
      ng L(-1) for estrone, <LOD (limit of detection) to 4.2 ng L(-1) for 17beta
      estradiol and 6.4 to 385.5 ng L(-1) for estriol. In the WWTP influent
      concentrations were 18.9 to 49.7 ng L(-1) for estrone, 2.4 to 12.7 ng L(-1), for
      17beta-estradiol and <LOQ (limit of quantitation) to 63.9 ng L(-1) for estriol.
      Reduced levels were found in the WWTP effluent: <7.1 ng L(-1) for estrone, <LOQ
      for 17beta-estradiol and <5.2 ng L(-1) for estriol. 17alpha-ethinylestradiol was
      detected in only one influent sample. Calculated estradiol equivalents (EEQ) were
      33.4, 22.4, 1.7 ng (EEQ) L(-1) in the hospital effluent, WWTP influent and WWTP
      effluent, respectively. Interestingly, the estrone: 17beta-estradiol:estriol
      ratio in the hospital effluent (1:0.1:9.4) is comparable to that found in the
      urine of pregnant women (1:0.3:20) indicating the most likely source of steroid
      estrogens. In WWTP influent the ratio was similar to that found in the non
      pregnant population. Our result recognise estriol as being one of the most
      important steroid estrogens, accounting for up to 92% of the total EEQ present in
      hospital samples and 37% and 46% in WWTP influent and effluent samples,
      respectively. The study reveals how concentrations of steroid estrogens vary on a
      daily basis and concludes that careful sampling strategies must be adopted when
      making a risk assessment. In addition, the low potency steroid estrogens that
      contribute towards overall estrogenicity of the sample, e.g. estriol, should be
      incorporated into environmental monitoring programs.

PMID- 21727966
TI  - Disposable microfluidic substrates: transitioning from the research laboratory
      into the clinic.
AB  - As more microfluidic applications emerge for clinical diagnostics, the choice of
      substrate and production method must be considered for eventual regulatory
      approval. In this review, we survey recent developments in disposable
      microfluidic substrates and their fabrication methods. We note regulatory
      approval for disposable microfluidic substrates will be more forthcoming if the
      substrates are developed with the United States Pharmacopeia's biocompatibility
      compliance guidelines in mind. We also review the recent trend in microfluidic
      devices constructed from a hybrid of substrates that takes advantage of each
      material's attributes.

PMID- 21727967
TI  - Assembly of glucagon (proto)fibrils by longitudinal addition of oligomers.
AB  - The process of glucagon peptide aggregation was studied with high resolution
      atomic force microscopy (AFM). The statistical analysis of ex situ AFM images in
      combination with in situ AFM observation suggests that it is more likely that
      (proto)fibrils are formed via direct longitudinal growth of oligomers, instead of
      the lateral association of two or more filaments.

PMID- 21727968
TI  - Seed-less amino-sugar mediated synthesis of gold nanostars.
AB  - By using aminosugars, a series of multipodal gold nanostructures has been
      obtained via a one-pot chemical reduction method in aqueous solution and at room
      temperature. The size and shape of these NPs were controlled either by adjusting
      the amount of reducing agent or by quenching the reaction at a given time.

PMID- 21727969
TI  - Chemoenzymatic synthesis of biotin-appended analogues of gangliosides GM2, GM1,
      GD1a and GalNAc-GD1a for solid-phase applications and improved ELISA tests.
AB  - Biotinylated analogues of gangliosides GM2, GM1, GD1a and GalNAc-GD1a were
      synthesized in high yields using glycosyltransferases from Campylobacter jejuni.
      The presence of a biotin moiety in the aglycone part of these mimics allows for
      attachment of these materials onto various streptavidin-coated surfaces. Analysis
      of the interaction of biotin-appended GM1 with the B subunit of Escherichia coli
      heat-labile enterotoxin performed in a modified ELISA procedure shows the
      potential of this compound to replace the natural GM1 in toxin detection.

PMID- 21727970
TI  - A synergistic approach to polycyclics via a strategic utilization of Claisen
      rearrangement and olefin metathesis.
AB  - Olefin metathesis promoted by a well-defined metal carbene complex has evolved
      into an efficient method for the construction of a broad range of carbocyclic and
      heterocyclic rings of varying size. The synthetic potential of the olefin
      metathesis has been further increased by combining various other C-C bond forming
      processes either in tandem or in sequence. Herein, application of Claisen
      rearrangement and olefin metathesis to prepare various intricate and/or
      biologically important targets has been described.

PMID- 21727971
TI  - Co-ligand-directed structural and magnetic diversities in an anisotropic Co(II)
      triazolate system.
AB  - Three novel 3,5-diamino-1,2,4-triazole (Hdatrz)-based Co(II) coordination
      complexes, [Co(Hdatrz)(0.5)(H(2)O)(2)(btec)(0.5)](n) (1),
      {[Co(Hdatrz)(Hbtc)].H(2)O}(n) (2) and [Co(2)(datrz)(2)(nb)(2)](n) (3) (H(4)btec =
      1,2,4,5-benzenetetracarboxylic acid, H(3)btc = 1,3,5-benzenetricarboxylic acid
      and Hnb = 4-nitrobenzoic acid), were synthesized by incorporating different
      carboxylate-containing co-ligands and then were structurally and magnetically
      characterized. Complex 1 is a 3D pillared-layer framework with corrugated Co(II)
      btec(4-) layers supported by neutral MU(2)-N1, N4-Hdatrz ligands. In contrast,
      the other two complexes are chiral (4, 4)- and racemic (4, 8(2))-topological
      layers with asymmetric MU(2)-N1, N4-Hdatrz-bridged helical chains extended by bis
      monodentate Hbtc(2-) ligands for 2 and with a MU(3)-N1, N2, N4-datrz((-))
      aggregated Shastry-Sutherland magnetic layer for 3. More interestingly, different
      magnetic phenomena with a field-induced metamagnetic transition from
      antiferromagnetic ordering to a ferromagnetic state for 1, spin-canted
      antiferromagnetism with a T(N) lower than 2.0 K for 2, as well as the coexistence
      of spin frustration and spin-flop transitions for 3 were observed, which,
      significantly, are governed by the local low-dimensional magnetic motifs mediated
      by the carboxylate and/or triazolate heterobridges in the anisotropic Co(II)
      triazolate system.

PMID- 21727972
TI  - Modification of the magnetic properties of a heterometallic wheel by inclusion of
      a Jahn-Teller distorted Cu(II) ion.
AB  - An investigation into the physical consequences of including a Jahn-Teller
      distorted Cu(II) ion within an antiferromagnetically coupled ring,
      [R(2)NH(2)][Cr(7)CuF(8)((O(2)C(t)Bu)(16))] is reported. Inelastic neutron
      scattering (INS) and electron paramagnetic resonance (EPR) spectroscopic data are
      simulated using a microscopic spin Hamiltonian, and show that the two Cr-Cu
      exchange interactions must be inequivalent. One Cr-Cu exchange is found to be
      antiferromagnetic and the other ferromagnetic. The geometry of the Jahn-Teller
      elongation is deduced from these results, and shows that a Jahn-Teller elongation
      axis must lie in the plane of the Cr(7)Cu wheel; the elongation is not observed
      by X-ray crystallography, due to positional disorder of the Cu site within the
      wheel. An electronic structure calculation confirms the structural distortion of
      the Cu site.

PMID- 21727977
TI  - Update on selective oxidation using gold.
AB  - This critical review aims to update the recent development in the selective
      oxidation of organic compounds by gold catalysis, highlighting the progress in
      the last three years. Following the impressive developments in the last decades,
      several protocols for catalytic oxidation are today available, which are based on
      the extraordinary properties of gold in terms of catalytic activity, selectivity,
      reusability and resistance to poisons. Beside many other applications, gold can
      be recommended for green processes dedicated to fine chemicals, pharmaceuticals
      and the food industry owing to its recognized bio-compatibility. The collected
      literature is focused on experiments concerning the oxidation of different
      chemical groups and could be of interest, in the wide area of organic chemistry,
      for improving previous processes or for exploring new catalytic pathways (174
      references).

PMID- 21727978
TI  - Identification of cytoplasmic and membrane-associated complexes in human
      embryonic stem cells using blue native PAGE.
AB  - Human embryonic stem cells (hESCs) have great potential for use in developmental
      biology studies, functional genomics applications, drug screening, and
      regenerative medicine. A detailed understanding of the molecular mechanisms that
      are responsible for maintaining the undifferentiated and pluripotent nature of
      hESCs is essential for their effective therapeutic application. It has become
      evident that many complex cellular processes are carried out by assemblies of
      protein molecules (protein complexes). Blue native polyacrylamide gel
      electrophoresis (BN-PAGE) has been used to separate protein complexes from whole
      cell lysates. Using BN-PAGE, we resolved cytoplasmic and membrane-associated
      complexes from hESCs and characterised their composition, stoichiometry, and
      dynamics by denaturing SDS-PAGE. The reliability of the fractionation was
      examined by western blot analysis of membrane and cytosolic markers. MALDI
      TOF/TOF mass spectrometry identified 119 cytosolic and 69 membrane proteins from
      the BN-PAGE proteome maps. Potential protein complexes were validated by
      computational prediction of possible protein-protein interactions using the
      Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.
      Based on BN-PAGE gels and validation by databases, 82 heteromultimeric and 47
      homomultimeric protein complexes have been found in hESCs. Resolving some of the
      protein complexes provided insight into the function of previously
      uncharacterised complexes in hESCs.

PMID- 21727979
TI  - A microfluidic system for fast detection of mitochondrial DNA deletion.
AB  - This study reports an integrated microfluidic system capable of automatic
      extraction and analysis of mitochondrial DNA (mtDNA). Mitochondria are the energy
      production and metabolism centres of human and animal cells, which supply most of
      the energy for maintaining physiological functions and play an important role in
      the process of cell death. Because it lacks an effective repair system, mtDNA
      suffers much higher oxidative damage and usually harbours more mutations than
      nuclear DNA. Alterations of mtDNA have been reported to be strongly associated
      with mitochondrial dysfunction, mitochondria-related diseases, aging, and many
      important human diseases such as diabetes and cancers. Thus, an effective tool
      for automatic detection of mtDNA deletion is in great need. This study,
      therefore, proposed a microfluidic system integrating three enabling modules to
      perform the entire protocol for the detection of mtDNA deletion. Crucial
      processes which included mtDNA extraction, nucleic acid amplification, separation
      and detection of the target genes were automatically performed. When compared
      with traditional assays, the developed microfluidic system consumed fewer samples
      and reagents, achieved a higher mtDNA extraction rate, and could automate all the
      processes within a shorter period of time (150 minutes). It may provide a
      powerful tool for the analysis of mitochondria mutations in the near future.

PMID- 21727980
TI  - Candida tenuis xylose reductase catalysed reduction of acetophenones: the effect
      of ring-substituents on catalytic efficiency.
AB  - The catalytic efficiencies of Candida tenuis xylose reductase catalysed
      reductions of mono-substituted acetophenones are in reasonable correlation with
      the sigma-Hammett coefficients of the substituted phenyl groups. Variations of
      the substrate transformation rates are hence mainly caused by mesomeric and
      inductive effects of the substituents, while differences in substrate binding
      have a secondary relevance. Some substrate (1)H NMR chemical shifts and carbonyl
      IR absorption bands are in reasonable accordance with the catalytic activities
      and allow the estimation of the transformation rates with good accuracy. The
      resulting substituted (S)-1-phenyl ethanols are generated in very high
      enantiomeric excess.

PMID- 21727981
TI  - Measuring gas-liquid partition coefficients of aroma compounds by solid phase
      microextraction, sampling either headspace or liquid.
AB  - Hydrophobic compounds are important odorants and nutrients in foods and
      beverages, as well as environmental contaminants and pharmaceuticals. Factors
      influencing their partitioning within multi-component systems and/or from the
      bulk liquid phase to the air are critical for understanding aroma quality and
      nutrient bioavailability. The equilibrium partitioning of hydrophobic analytes
      between air and water was analyzed using solid phase microextraction (SPME) in
      the headspace (HS-SPME) and via direct immersion in the liquid (DI-SPME). The
      compounds studied serve as models for hydrophobic aroma compounds covering a
      range of air-water partition coefficients that extends over four orders of
      magnitude. By varying the total amount of analyte as well as the ratio of vapor
      to liquid in the closed, static system, the partition coefficient, K(vl), can be
      determined without the need for an external calibration, eliminating many
      potential systematic errors. K(vl) determination using DI-SPME in this manner has
      not been demonstrated before. There was good agreement between results determined
      by DI-SPME and by HS-SPME over the wide range of partitioning behavior studied.
      This shows that these two methods are capable of providing accurate,
      complementary measurements. Precision in K(vl) determination depends strongly on
      K(vl) magnitude and the ratio of the air and liquid phases.

PMID- 21727982
TI  - Highly efficient electroosmotic flow through functionalized carbon nanotube
      membranes.
AB  - Carbon nanotube membranes with inner diameter ranging from 1.5-7 nm were examined
      for enhanced electroosmotic flow. After functionalization via electrochemical
      diazonium grafting and carbodiimide coupling reaction, it was found that neutral
      caffeine molecules can be efficiently pumped via electroosmosis. An
      electroosmotic velocity as high as 0.16 cm s(-1) V(-1) has been observed. Power
      efficiencies were 25-110 fold improved compared to related nanoporous materials,
      which has important applications in chemical separations and compact medical
      devices. Nearly ideal electroosmotic flow was seen in the case where the mobile
      cation diameter nearly matched the inner diameter of the single-walled carbon
      nanotube resulting in a condition of using one ion is to pump one neutral
      molecule at equivalent concentrations.

PMID- 21727983
TI  - Sized controlled synthesis, purification, and cell studies with silicon quantum
      dots.
AB  - This article describes the size control synthesis of silicon quantum dots with
      simple microemulsion techniques. The silicon nanocrystals are small enough to be
      in the strong confinement regime and photoluminesce in the blue region of the
      visible spectrum and the emission can be tuned by changing the nanocrystal size.
      The silicon quantum dots were capped with allylamine either a platinum catalyst
      or UV-radiation. An extensive purification protocol is reported and assessed
      using (1)H NMR to produce ultra pure silicon quantum dots suitable for biological
      studies. The highly pure quantum dots were used in cellular uptake experiments
      and monitored using confocal microscopy. The results showed that the amine
      terminated silicon nanocrystals accumulated in lysosome but not in nuclei and
      could be used as bio-markers to monitor cancer cells over long timescales.

PMID- 21727984
TI  - Photoreversible fragmentation of a liquid interface for micro-droplet generation
      by light actuation.
AB  - We describe a method to induce by light a reversible switch from a continuous two
      phase laminar flow to a droplet generating regime, in microfluidic devices with a
      usual water-in-oil flow focusing geometry. It consists in adding a photosensitive
      surfactant to the aqueous phase to modulate using light the interfacial energy
      between flowing liquids and the microfluidic substrate. We show that UV
      irradiation induces liquid fragmentation into monodisperse water microdroplets
      and that many cycles of reversible and rapid switches (<2 s) between continuous
      laminar flows and stable droplet regimes can be realized. By spatially
      controlling the application of the light stimulus, we also demonstrate the first
      spatially resolved remote induction of droplet generation.

PMID- 21727985
TI  - Experimental studies of surface reactions among OH radicals that yield H2O and
      CO2 at 40-60 K.
AB  - We investigated the OH-related formation routes of two astrophysically important
      molecules, H(2)O and CO(2), under relatively warm astrophysical conditions. OH
      radicals, together with other neutral species such as H, O, H(2), and O(2), were
      produced in H(2)O microwave-discharge plasma and cooled to 100 K before being
      deposited on an Al substrate at 40-60 K. H(2)O formed at 40 and 50 K, but not at
      60 K. Taking the experimental conditions into account, a possible route of H(2)O
      formation is via reactions involving OH + OH, which yield H(2)O(2) as the main
      reaction product. The present study is the first to show experimentally that
      surface reactions of two OH radicals can yield H(2)O at low temperatures. The
      products' branching ratio was 0.2 and 0.8 for H(2)O and H(2)O(2), respectively.
      When CO was co-deposited with neutral species that formed in the H(2)O plasma,
      CO(2) was formed at 40-60 K. H(2)CO(3) formed at 40 and 50 K. The present results
      may suggest that chemical reactions related to OH radicals are effective at
      yielding various molecules in relatively warm astrophysical environments, such as
      protostars.

PMID- 21727986
TI  - Structure-related variable responses of calcium sensitive MRI probes.
AB  - A new series of Gd(3+) complexes based on DO3A (GdL(1)-GdL(4)) was synthesized
      and investigated. They possess side chains with different structures which
      determine their varying binding properties and response towards endogenous metal
      ions, measured by changes in the longitudinal relaxivity (r(1)). GdL(4) exhibits
      the highest selectivity toward Ca(2+) in comparison to the other complexes, with
      up to a 63% increase of the r(1). GdL(2) and GdL(3) also respond to different
      Ca(2+) concentration ranges, however with a lower selectivity since the r(1)
      changes are also observed in the presence of other cations such as Mg(2+), Zn(2+)
      or Cu(2+). Assessment of the hydration number (q) via luminescence lifetime
      measurements confirmed that the change in q is responsible for the r(1) response
      for all the complexes.

PMID- 21727987
TI  - Synthesis of the proposed structure of phaeosphaeride A.
AB  - The first total synthesis of the proposed structure of phaeosphaeride A has been
      achieved via six-membered-ring formation by means of an intramolecular vinyl
      anion aldol reaction as the key step. This synthesis suggests a revised
      configurational assignment for phaeosphaeride A.

PMID- 21727988
TI  - Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression
      through a suppression of PPAR alpha/gamma activity in microvascular endothelial
      cells.
AB  - Microvascular dysfunction occurs in insulin resistance and/or hyperinsulinaemia.
      Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins
      (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting
      with CD36, a PPARalpha/gamma-regulated scavenger receptor and long-chain FFA
      transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake
      before and after insulin treatment in human dermal microvascular endothelial
      cells (HMVECs), +/- different types of fatty acids (FA), including palmitic,
      oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA)
      acids. Insulin (10(-8) and 10(-7) M) time-dependently increased DiI-oxLDL uptake
      and CD36 surface expression (by 30 +/- 13%, p<0.05 vs. untreated control after 24
      hours incubation), as assessed by ELISA and flow cytometry, an effect that was
      potentiated by the PI3-kinase inhibitor wortmannin and reverted by the ERK1/2
      inhibitor PD98059 and the PPARalpha/gamma antagonist GW9662. A >= 24 hour
      exposure to 50 MUM DHA or EPA, but not other FA, blunted both the constitutive
      (by 23 +/- 3% and 29 +/- 2%, respectively, p<0.05 for both) and insulin-induced
      CD36 expressions (by 45 +/- 27 % and 12 +/- 3 %, respectively, p<0.05 for both),
      along with insulin-induced uptake of DiI-oxLDL and the downregulation of
      phosphorylated endothelial nitric oxide synthase (P-eNOS). At gel shift assays,
      DHA reverted insulin-induced basal and oxLDL-stimulated transactivation of PPRE
      and DNA binding of PPARalpha/gamma and NF-kappaB. In conclusion, omega-3 fatty
      acids blunt the increased CD36 expression and activity promoted by high
      concentrations of insulin. Such mechanisms may be the basis for the use of omega
      3 fatty acids in diabetic microvasculopathy.

PMID- 21727989
TI  - [Optimization of the fine needle aspiration biopsy (FNAB) of thyroid nodules-
      automatic aspirator versus manual technique].
AB  - OBJECTIVE: Optimization of a specially developed automatic microaspirator for
      fine-needle aspiration of suspicious thyroid nodules. PATIENTS, METHOD: In a
      preliminary test biopsy effectiveness was evaluated in 20 native resected thyroid
      glands in vitro with both a Cameco(r) gun and a specially designed microaspirator
      respectively. In addition in both techniques two different needles (21-G and 27
      G) were used to evaluate the influence of these two cannula. Subsequently, 103
      thyroid nodules were biopsied in vivo and compared the results with a preliminary
      series of the same physician. In the workup and evaluation of the cytology the
      ThinPrep(r) technology was used. RESULTS: In vitro the automatic microaspirator
      was superior to Cameco gun in both when using the 21-Gauge and the 27-Gauge
      needle. In terms of needle sizes a statistically significant difference at the
      95% confidence level was evident for both comparisons in favor of 21-gauge
      needle. In vivo, 91% of punctures with the microaspirator were usable, while in
      the pre-series only 84% were usable (p>0.05). CONCLUSION: The automatic
      microaspirator is superior to the manual aspiration. Moreover, under sonographic
      control it is more convenient, to biopsy even very small nodules and lesiosn
      (down to 4 mm in diameter).

PMID- 21727990
TI  - Preoperative risk stratification using (18)F-FDG PET/CT in women with endometrial
      cancer.
AB  - The aim of this study is to evaluate the usefulness of (18)F-FDG PET/CT for
      preoperative stratification of high-risk and low-risk carcinomas in patients with
      endometrial cancer. PATIENTS, METHODS: 60 women (mean age 53.8+/-9.9 years) with
      endometrial cancer, who underwent (18)F-FDG PET/CT for preoperative staging work
      up, followed by primary cytoreductive surgery, were enrolled in this study.
      Maximum and mean standardized uptake values (SUVmax, SUVmean) of endometrial
      tumors were measured, and compared with the various clinicopathologic findings
      obtained after surgery. Tumour aggressiveness was classified as high-risk and low
      risk carcinomas. Patients with stage I or II, endometrioid adenocarcinoma,
      histologic grade 1 or 2, invasion of less than half of the myometrium, maximum
      tumor size less than 2.0 cm, and absence of cervical invasion and lymphovascular
      space involvement (LVSI) were classified as the low-risk carcinoma group. The
      remaining patients were classified as the high-risk carcinoma group. RESULTS: In
      univariate analysis, SUVmax of the primary endometrial tumor was significantly
      higher in patients who were in a postmenopausal state (p=0.047), large (>2 cm)
      primary tumor (p<0.001), nonendometrioid subtype (p=0.024), invasion of more than
      half of the myometrium (p=0.020), or LVSI (p=0.004). SUVmax differed
      significantly according to FIGO stage (p=0.013) and histologic grade (p<0.001).
      In multivariate analysis, FIGO stage, histologic grade, LVSI, and maximum tumor
      size demonstrated a significant association with SUVmax (p<0.001; r=0.843,
      r(2)=0.711). SUVmean showed similar results. Forty-one (68.3%) patients were
      diagnosed postoperatively as high-risk and 19 patients (31.7%) as low-risk
      carcinoma. Patients with high-risk carcinoma (12.1+/-6.1) showed significantly
      higher SUVmax than patients with low-risk carcinoma (5.8+/-2.8, p<0.001). The
      optimal SUVmax cut-off value of 8.7, determined by ROC analysis, revealed 75.6%
      sensitivity, 89.5% specificity, and 81.7% accuracy for risk stratification.
      CONCLUSION: High-risk endometrial cancer might be differentiated by means of
      higher SUVmax from low-risk endometrial cancer. (18)F-FDG FDG PET/CT can be
      applied preoperatively for stratification of risk in patients with endometrial
      cancer.

PMID- 21727991
TI  - Occupational social class and disability retirement among municipal employees-
      the contribution of health behaviors and working conditions.
AB  - OBJECTIVES: The mechanisms through which a low socioeconomic position leads to
      disability retirement are not yet established. We examined, on the one hand, the
      associations between occupational social class and disability retirement due to
      all causes, musculoskeletal diseases, and mental disorders and, on the other
      hand, the contribution of health behaviors and working conditions to these
      associations. METHODS: Middle-aged municipal employees from the Helsinki Health
      Study cohort baseline surveys in 2000-2002 (N=6516) were followed up until the
      end of 2010 for disability retirement. Retirement data were obtained from the
      registers of the Finnish Centre for Pensions and social class and covariates from
      the baseline surveys. Social class was categorized into managers and
      professionals, semi-professionals, routine non-manual employees, and manual
      workers. Cox regression analysis was used to calculate hazard ratios and their
      95% confidence intervals. RESULTS: The risk of disability retirement was
      generally higher among those in lower social classes with a strong gradient for
      all causes, an even stronger gradient for musculoskeletal diseases, and a weaker
      non-linear association for mental disorders. These associations were largely
      mediated through physical workload among both women and men and hazardous
      exposures particularly among men. In mental disorders, job control also mediated
      the association. Strenuous desktop work and job demands widened the social class
      differences particularly among men and in mental disorders. The contribution of
      health behaviors was modest. CONCLUSIONS: Improvements particularly in the
      physical working conditions but also the job control of those in lower social
      classes are likely to reduce socioeconomic differences in disability retirement.

PMID- 21727992
TI  - A fatal case of hot air sauna burn in an elderly patient initially misdiagnosed
      as bullous pemphigoid.

PMID- 21727993
TI  - Antimicrobial effects of plasma-mediated bipolar radiofrequency ablation on
      bacteria and fungi relevant for wound infection.
AB  - Infection constitutes an important part of wound pathology and impedes wound
      healing. Plasma-mediated bipolar radiofrequency ablation (Coblation((r))) is a
      tissue-removal technique suggested for use in wound treatment. The aims of this
      study were to determine the antimicrobial effect of ablation exposure on bacteria
      and fungi relevant to wound infection, and how exposure time, temperature and
      aerobic/anaerobic growth influence the effect. Suspensions of 10(6) colony
      forming units/ml of Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas
      aeruginosa, Escherichia coli and Candida albicans were exposed to ablation or
      thermal control for 500, 1000 or 2000 ms, or left untreated, and incubated
      aerobically. E. coli was also incubated anaerobically. Ablation was significantly
      (p < 0.0001) microbicidal on all strains compared with untreated and thermal
      control. The reductions compared with untreated control were 99.87-99.99% for all
      strains. In conclusion, plasma-mediated bipolar radio-frequency ablation has a
      general microbicidal effect in vitro on microbes relevant to wound infection
      independent of aerobic/anaerobic growth and thermal effect.

PMID- 21727994
TI  - Signet-Ring Cell Carcinoma of the Gallbladder after Gastric Bypass.

PMID- 21727995
TI  - Serum levels of fatty acid synthase in colorectal cancer patients are associated
      with tumor stage.
AB  - PURPOSE: Fatty acid synthase is a common phenotype to various human cancers
      including those of prostate, colon, lung, endometrium, and stomach. Increased
      fatty acid synthase levels have been detected in serum from patients with breast
      and pancreatic cancer. In this study, serum levels of fatty acid synthase were
      measured in colorectal cancer patients at different stages of disease. METHODS:
      Consecutive 67 patients with colorectal cancer were enrolled in the study. Serum
      levels of fatty acid synthase were examined by ELISA test. The Kruskal-Wallis
      test and the chi (2) method for trend have been used to analyze data. RESULTS:
      Serum fatty acid synthase levels of patients belonging to three groups of stage
      disease are statistically different. The patients with stage III and IV have
      significantly higher serum levels of fatty acid synthase than patients with stage
      I-II. There is a positive trend in serum fatty acid synthase levels from stage I
      II to stage III and IV of disease. CONCLUSIONS: Fatty acid synthase levels are
      associated with the stage of disease in patients with colorectal cancer.

PMID- 21727996
TI  - Direct quantification of cannabinoids and cannabinoid glucuronides in whole blood
      by liquid chromatography-tandem mass spectrometry.
AB  - The first method for quantifying cannabinoids and cannabinoid glucuronides in
      whole blood by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was
      developed and validated. Solid-phase extraction followed protein precipitation
      with acetonitrile. High-performance liquid chromatography separation was achieved
      in 16 min via gradient elution. Electrospray ionization was utilized for
      cannabinoid detection; both positive (Delta(9)-tetrahydrocannabinol [THC] and
      cannabinol [CBN]) and negative (11-hydroxy-THC [11-OH-THC], 11-nor-9-carboxy-THC
      [THCCOOH], cannabidiol [CBD], THC-glucuronide, and THCCOOH-glucuronide) polarity
      were employed with multiple reaction monitoring. Calibration by linear regression
      analysis utilized deuterium-labeled internal standards and a 1/x(2) weighting
      factor, yielding R(2) values >0.997 for all analytes. Linearity ranged from 0.5
      to 50 MUg/L (THC-glucuronide), 1.0-100 MUg/L (THC, 11-OH-THC, THCCOOH, CBD, and
      CBN), and 5.0-250 MUg/L (THCCOOH-glucuronide). Imprecision was <10.5% CV,
      recovery was >50.5%, and bias within +/-13.1% of target for all analytes at three
      concentrations across the linear range. No carryover and endogenous or exogenous
      interferences were observed. This new analytical method should be useful for
      quantifying cannabinoids in whole blood and further investigating cannabinoid
      glucuronides as markers of recent cannabis intake.

PMID- 21727997
TI  - Improved prediction of fellow-eye response in one-eye trials using multiple
      intraocular pressure measurements.
AB  - PURPOSE: To examine the effects of multiple intraocular pressure (IOP)
      measurements on the correlation of response to glaucoma medication between fellow
      eyes. METHODS: Latanoprost was applied to the first eye and then to both eyes of
      16 patients with either primary open-angle glaucoma or ocular hypertension. IOP
      measurements were performed twice on different days for each of three periods: at
      baseline, during treatment of the first eye only and for both eyes. IOP decreases
      in the first and second eyes were evaluated with ?IOP 1 (=IOP at baseline - IOP
      after treatment) and ?IOP 2 (=?IOP 1 - IOP fluctuation of the contralateral eye).
      The correlation of IOP decreases between the fellow eyes was analyzed by linear
      regression analysis using the Pearson correlation coefficient, r. RESULTS: No
      significant correlations of ?IOP1 between fellow eyes were found regardless of
      the number of IOP measurements. ?IOP2 was significantly correlated between fellow
      eyes using two post-treatment IOP measurements, but not with a single post
      treatment IOP. CONCLUSIONS: Using multiple post-treatment IOP measurements may
      improve the prediction of a fellow eye's response to glaucoma medication in one
      eye trials.

PMID- 21727998
TI  - Effective palliation and quality of life outcomes in studies of surgery for
      advanced, non-curative gastric cancer: a systematic review.
AB  - BACKGROUND: Relief of symptoms should be the primary focus of palliative
      treatment as defined by the World Health Organization. Evaluating the
      effectiveness of palliative interventions should incorporate this goal and
      include quality of life (QOL) outcome assessments. A systematic review of the
      surgical gastric cancer literature was performed to summarize the effectiveness
      of palliative surgical interventions in addressing QOL. METHODS: An electronic
      literature search of EMBASE, Medline, and the Cochrane Database of Controlled
      Trials was performed from January 1, 1985 to December 1, 2009. English language
      abstracts and articles were reviewed independently by two reviewers. A systematic
      approach to data abstraction and presentation was followed. RESULTS: No articles
      were identified as reporting true QOL outcomes using reliable, validated QOL
      instruments in surgically managed, advanced gastric cancer patients. Nine
      articles were identified as reporting outcomes measuring effectiveness of
      palliation. Commonly reported pre-procedure symptoms were weight loss, abdominal
      pain, vomiting, obstruction, and bleeding. Time to oral intake was reported in 5
      of 9 studies, ranging from a mean of 2.9 days (laparoscopic gastrojejunostomy) to
      8 days (surgical bypass). Length of postoperative inpatient stay ranged from a
      mean of 7 days (gastrojejunostomy) to 28 days (surgical bypass). Other measures
      of effective palliation included measures of clinical success, hospital re
      admission rates, and post-procedure analgesic intake. CONCLUSION: A paucity of
      literature exists regarding the QOL of surgically managed gastric cancer
      patients. Prospectively designed studies using credible QOL measures are
      necessary to better inform the treatment decision-making process for these
      patients.

PMID- 21727999
TI  - Evaluation of the combined use of adiponectin and C-reactive protein levels as
      biomarkers for predicting the deterioration in glycaemia after a median of 5.4
      years.
AB  - AIMS/HYPOTHESIS: Hypoadiponectinaemia and raised C-reactive protein (CRP) level
      are obesity-related biomarkers associated with glucose dysregulation. We
      evaluated the combined use of these two biomarkers in predicting the
      deterioration of glycaemia in a prospective study after a median of 5.4 years.
      METHODS: In total 1,288 non-diabetic participants from the Hong Kong
      Cardiovascular Risk Factor Prevalence Study-2, with high-sensitivity CRP (hsCRP)
      and total adiponectin levels measured were included. OGTT was performed in all
      participants. Two hundred and six participants had deterioration of glycaemia at
      follow-up, whereas 1,082 participants did not. RESULTS: Baseline age, hsCRP and
      adiponectin levels were significant independent predictors of the deterioration
      of glycaemia in a Cox regression analysis after adjusting for baseline age, sex,
      BMI, hypertension, triacylglycerols, 2 h post-OGTT glucose and homeostasis model
      assessment of insulin resistance index (all p < 0.01). The introduction of hsCRP
      or adiponectin level to a regression model including the other biomarker improved
      the prediction of glycaemic progression significantly in all participants,
      especially in women (all p < 0.01). The combined inclusion of the two biomarkers
      resulted in a modest improvement in model discrimination, compared with the
      inclusion of either one alone. Among participants with impaired fasting
      glucose/impaired glucose tolerance (IFG/IGT) at baseline, hsCRP and adiponectin
      levels were not predictive of progression or improvement of glycaemic status.
      CONCLUSIONS/INTERPRETATION: Adiponectin and hsCRP levels are independent factors
      in predicting the deterioration of glycaemia, supporting the role of adiposity
      related inflammation in the development of type 2 diabetes. Their combined use as
      predictive biomarkers is especially useful in women, but not in participants with
      IFG/IGT.

PMID- 21728002
TI  - Curative-intent stereotactic body radiation therapy for residual breast cancer
      liver metastasis after systemic chemotherapy.
AB  - Liver metastases from breast cancer are generally treated with systemic therapy
      such as chemotherapy or hormonotherapy. However, local treatment options such as
      resection, radiofrequency ablation (RFA), and radiotherapy can also be considered
      to treat oligometastases. We report the case of a 45-year-old female treated with
      stereotactic body radiotherapy (SBRT) after chemotherapy against a solitary liver
      metastasis from primary breast cancer. A liver metastasis with diameter of 35 mm
      developed 3.5 years after surgery for primary breast cancer in 2004. Fourteen
      courses of triweekly docetaxel treatments considerably decreased the metastatic
      lesion, but there still remained a tiny lesion radiographically. Chemotherapy was
      stopped because of the side-effects of docetaxel, and then SBRT was selected for
      additional treatment, aiming at complete cure of metastasis. X-ray irradiation
      (52.8 Gy/4 fractions) was applied to the remaining metastatic lesion, and
      magnetic resonance imaging (MRI) showed no evidence of residual tumor 4 months
      after irradiation. Neither regrowth nor recurrences have been found until now, 24
      months after SBRT. SBRT for oligometastases of breast cancer may be one of the
      possible curative-intent options, being less invasive than surgical resection or
      RFA.

PMID- 21728000
TI  - Gastrointestinal stem cells in self-renewal and cancer.
AB  - The gastrointestinal epithelium is a unique model for the study of mammalian stem
      cells. Not only does it have a highly stereotypical organization, its remarkable
      rate of self-renewal provides a daily readout of stem cell activity. The past
      decade has seen a major investment in developing technologies dedicated to
      revealing the identity of the long-elusive gastrointestinal stem cells. An array
      of purported stem cell biomarkers is now available for the mouse, including
      surface-expressed proteins that hold great promise as antibody targets for use in
      isolating human stem cells. Here we critically appraise the validity of these
      biomarkers and discuss their likely impact on our understanding of stem cell
      roles in self-renewal and cancer in the gastrointestinal tract.

PMID- 21728003
TI  - The different expression of immune-related cytokine genes in response to
      velogenic and lentogenic Newcastle disease viruses infection in chicken
      peripheral blood.
AB  - Newcastle disease virus (NDV) is an important pathogen hazardous to poultry
      industry, and the pathogenicity of NDV strains varies with different virulence.
      Peripheral blood serves as an important producer and carrier of viruses and
      cytokines in NDV infection. In order to explore the difference of cytokine
      expression in the peripheral blood between velogenic strain and lentogenic strain
      infection, NDV virulent strain F48E9 and vaccine strain Lasota were used to
      infect specific-pathogen-free (SPF) chickens separately, and peripheral blood was
      collected on 0, 3, 7, 10, 14, and 21 days post-infection (d.p.i.). Real-time PCR
      was then used to detect the expression of six kinds of immune-related cytokine
      genes. For the F48E9 group, a sharp increase of the expression of interferon
      alpha (IFN-alpha), interferon-gamma (IFN-gamma), interleukin-16 and IL-18 was
      observed on 3 d.p.i. before the NDV blood peak (7 d.p.i.), followed by a rapid
      decline to the level lower than that of control group, then the expression of IFN
      alpha increased slowly and reached or exceeded the level of control group in the
      later phase of the infection, while the expression of IFN-gamma, IL-16, and IL-18
      fluctuated at the level of control group for the rest of study period. The
      increase of IL-2 expression was not obvious, and no increase of IL-15 expression
      was noted. For the Lasota (vaccine) group, the picture was quite different, a
      sharp increase of IFN-gamma (but not IFN-alpha), IL-2 was observed on 7 d.p.i.
      before the NDV blood peak (10 d.p.i.). On the contrary, there was no dramatic
      increase of IL-16 and IL-18. Interestingly, in contrast to the F48E9 group, there
      was an increase of IL-15 on day 10 d.p.i., but it remained modest. There was also
      an increase of IFN-alpha on day 21 d.p.i. Our results revealed that infection
      with NDV strains of different virulence was associated with distinct cytokine
      expression patterns in peripheral blood, modulation of cytokine responses may
      play a key role in mediation of NDV pathogenesis.

PMID- 21728004
TI  - Berbamine overcomes imatinib-induced neutropenia and permits cytogenetic
      responses in Chinese patients with chronic-phase chronic myeloid leukemia.
AB  - During imatinib therapy, many patients with chronic myeloid leukemia (CML)
      develop severe neutropenia, leading to treatment interruptions, and potentially
      compromising response to imatinib. Berbamine (a bisbenzylisoquinoline alkaloid)
      has been widely used in Asian countries for managing leukopenia associated with
      chemotherapy. To investigate whether berbamine shows clinical benefit in
      reversing imatinib-associated neutropenia, we analyzed 63 chronic-phase CML
      patients who had developed grade >=2 neutropenia and were treated with (n = 34,
      berbamine group) or without (n = 29, control group) berbamine. Among those
      patients with grade 2 neutropenia, five of 13 (38.5%) progressed to grade 3
      neutropenia without berbamine support, while in the berbamine group, the rate
      decreased to 3/20 (15%) (p = 0.213). Although the rate of recovery from grade >=3
      neutropenia was similar in the two groups (94.1 vs. 90.5%, p = 0.559), berbamine
      markedly shortened the recovery time (median, 11 vs. 24 days, p = 0.006), and
      prevented recurrence of grade >=3 neutropenia (18.8 vs. 52.6%, p = 0.039).
      Moreover, with berbamine support, the time to achieve complete cytogenetic
      response was significantly shorter (median, 6.5 vs. 10 months, p = 0.007). There
      were no severe adverse events associated with berbamine treatment. In conclusion,
      the present study reveals the potential clinical value of berbamine in the
      treatment of CML with imatinib-induced neutropenia. The use of berbamine may
      improve response to imatinib by stimulating normal hematopoiesis and faster
      neutropenia recovery.

PMID- 21728006
TI  - [Algorithm for the treatment of anastomotic failure after laparoscopic
      prostatectomy].
AB  - Laparoscopic (transperitoneal) radical prostatectomy is a standard procedure for
      surgical management of locally advanced prostate cancer. Disagreement still
      prevails over how long the catheter should remain in place and whether
      cystography is indicated before catheter removal. Until recovery, the urine is
      drained through a transurethral indwelling catheter. Serious complications due to
      anastomotic leakage could be avoided in our patient cohort by applying the
      algorithm presented.

PMID- 21728005
TI  - Renal amyloidosis caused by apolipoprotein A-II without a genetic mutation in the
      coding sequence.
AB  - Although the majority of renal amyloidosis is caused by either acquired
      monoclonal immunoglobulin light-chain amyloidosis or reactive systemic amyloid A,
      some cases are caused by hereditary amyloidosis. Apolipoprotein A-II (apoAII)
      amyloidosis is a rare form of hereditary amyloidosis and cannot be diagnosed by a
      routine examination. Thus, the prevalence and etiology of apoAII amyloidosis are
      uncertain. In humans, a genetic mutation in the stop codon of apoAII is
      considered to be a cause of amyloid fibril formation. We report on a 68-year-old
      man who presented with proteinuria by apoAII amyloidosis without family history.
      His proteinuria gradually increased to 6 g/day within 1 year. A renal biopsy
      showed amyloid deposition in the glomeruli, however, acquired monoclonal
      immunoglobulin light-chain amyloidosis and reactive systemic amyloid A were ruled
      out. Immunohistochemistry revealed apoAII deposition in the glomeruli, but DNA
      sequencing did not identify any genetic mutation in the coding sequence of
      apoAII. Here, we report a case of apoAII amyloidosis without a genetic mutation
      in the coding sequence and discuss the etiology of apoAII amyloidosis.

PMID- 21728007
TI  - [Intestinal neobladder fistula after radical cystectomy and orthotopic ileal
      neobladder].
AB  - Intestinal neobladder fistula is one of the rare complications following radical
      cystectomy which is described in about 1.5-2% of all patients. We report on 2 of
      267 consecutive patients who underwent radical cystectomy with an orthotopic
      neobladder who developed such a fistula. Both patients presented initially with
      recurrent urinary tract infections, fever and chills. In both cases the final
      diagnosis was made after oral intake of poppy seeds. Imaging studies of choice to
      identify the anatomical localisation of the fistula and to exclude accompanying
      intra-abdominal fluid collections were made by computed tomography and magnetic
      resonance imaging. The treatment of choice consists of surgical excision of the
      fistula, double-layer closure of the neobladder and small bowel resection or
      double-layer closure depending on the size of the fistula. A conservative
      approach only seems to be justified in patients with significant comorbidities or
      very small fistulas without systemic symptoms.

PMID- 21728009
TI  - [Introduction of interdisciplinary prostate cancer centers based on the
      recommendations of the German Cancer Society. A cost-benefit analysis 3 years
      after accreditation].
AB  - The introduction of prostate cancer treatment centers according to the criteria
      of the German Cancer Society ("Deutsche Krebsgesellschaft", DKG) aims at
      improving the quality of care for patients with prostate cancer. Systematic
      analyses of the effects and costs are lacking as yet. Three years after
      certification of the Interdisciplinary Prostate Cancer Center at the Charite
      Hospital Berlin we observed a decrease in the rate of positive surgical margins
      (tumor stage pT2), but other parameters of treatment quality including patient
      satisfaction remained unchanged. A survey among urologists of the region showed a
      high acceptance of prostate cancer centers in general. The majority of
      participating urologists appreciated the work of the Charite center, in
      particular the treatment recommendations given by the center were mostly followed
      and the majority of urologists regularly use educational activities of the
      center. However, only 30% of the participating urologists confirmed short-term
      improvements in the quality of patient care. Yearly additional costs for the
      Charite prostate cancer center are estimated at 205,000 euro (precertification
      phase and certification) and 138,000 euro (monitoring phase), despite the initial
      drop in mean treatment costs per case (radical prostatectomy). The introduction
      of prostate cancer treatment centers certified by the DKG is cost intensive,
      increases in treatment efficiency notwithstanding. Short-term improvements in
      quality of care cannot be unequivocally demonstrated. Prostate cancer centers
      serve an important role in counseling and medical education and may thus help
      disseminate evidence-based treatment strategies.

PMID- 21728008
TI  - [From tumor tissue via primary cultures to xenograft models: a functional
      approach in prostate cancer research].
AB  - The clinical course of prostate cancer, the most common cancer in men, is very
      variable. Despite intense research activities over the years and besides
      histopathological criteria, prognostic markers that reliably predict tumor
      behavior and the necessity for treatment are still missing. A likely explanation
      for this fact is the lack of good tumor models, mimicking the in vivo situation.
      These models are not only essential for a better understanding of the
      pathogenesis of prostate cancer but also play an important role in the
      development of new therapeutic strategies. Since results of permanent cell
      culture experiments reflect only in part real tumor behavior and primary cultures
      from patient material cannot be grown indefinitely, novel approaches need to be
      developed to achieve reliable and clinically relevant prostate cancer research.In
      this work the development of several approaches for culturing primary prostate
      cancer tissue is illustrated and a forecast of future research plans utilizing
      xenograft models in mice is made.

PMID- 21728010
TI  - [Robotic surgery in paediatric urology: current status and perspectives].
AB  - The increasing experience obtained through laparoscopy has resulted in the
      evolution of ablative and reconstructive procedures in the field of paediatric
      urology. Apart from the established methods of laparoscopic nephrectomy and
      orchidopexy, nowadays laparoscopic hemi-nephrectomy and pyeloplasty have become
      standard therapeutic surgical alternatives. Nevertheless, many of these
      procedures require a high level of experience in laparoscopic preparation and
      stitching techniques and are thus performed in institutions with greater
      laparoscopic experience. With the introduction and evolution of the robotic
      assisted technique and the availability of smaller instruments and ports (8 and 5
      mm), there has been an evolution in the spectrum of complex ablative and
      reconstructive procedures in the field of paediatric urology as well.
      Nevertheless, there is a lack of randomised trails and the literature available
      in this area consists manly of case reports. The purpose of this article is to
      present the current status and perspectives of robotic-assisted surgery in the
      field of paediatric urology.

PMID- 21728011
TI  - [Treatment for overactive bladder].
AB  - BACKGROUND: Epidemiological data demonstrate an increasing prevalence of symptoms
      of overactive bladder (OAB) with age not only in women, but especially in men.
      Despite a comparable prevalence, however, men are still highly underrepresented
      in most large randomized studies on the effect of antimuscarinic drugs. QUESTION:
      In this subgroup analysis of the CAP Study the efficacy and tolerability of
      solifenacin was examined in 111 men with symptoms of OAB. The study was performed
      in a network between general practitioners and urologists under routine
      conditions over a period of 12 months. RESULTS: Treatment with solifenacin
      reduced all symptoms of OAB significantly, and the use of pads decreased by more
      than half. The tolerability of therapy was judged as "excellent" or "good" by
      over 95% of doctors and patients. CONCLUSION: This subgroup analysis of the CAP
      Study confirms the good efficacy and tolerability of solifenacin in male OAB in
      daily practice over a treatment period of 1 year.

PMID- 21728012
TI  - Erratum to: Treating rheumatoid arthritis to target: an international initiative.

PMID- 21728013
TI  - Robotic assisted total hip arthroplasty using the MAKO platform.
AB  - Surgeons want to perform a perfect total hip replacement (THR) with every
      operation. Human performance has limitations, especially when performing a
      mechanical operation in a biological environment. Recent suggested changes to
      improve outcomes have been large femoral heads and anterior incisions, but
      unfortunately neither has resulted in any scientific data that change has been
      effected. The scientific data does tell us that poor component positions and
      impingement are the source of increasing mechanical complications. Therefore,
      attempts to improve the surgeon's performance by precise quantitative knowledge
      in the operating room have been used. We discuss robotic guided navigation as a
      solution. This technology provides predictable and reproducible results.

PMID- 21728014
TI  - Egomotion estimation with optic flow and air velocity sensors.
AB  - We develop a method that allows a flyer to estimate its own motion (egomotion),
      the wind velocity, ground slope, and flight height using only inputs from onboard
      optic flow and air velocity sensors. Our artificial algorithm demonstrates how it
      could be possible for flying insects to determine their absolute egomotion using
      their available sensors, namely their eyes and wind sensitive hairs and antennae.
      Although many behaviors can be performed by only knowing the direction of travel,
      behavioral experiments indicate that odor tracking insects are able to estimate
      the wind direction and control their absolute egomotion (i.e., groundspeed). The
      egomotion estimation method that we have developed, which we call the opto
      aeronautic algorithm, is tested in a variety of wind and ground slope conditions
      using a video recorded flight of a moth tracking a pheromone plume. Over all test
      cases that we examined, the algorithm achieved a mean absolute error in height of
      7% or less. Furthermore, our algorithm is suitable for the navigation of aerial
      vehicles in environments where signals from the Global Positioning System are
      unavailable.

PMID- 21728015
TI  - Biodegradation kinetics of 4-fluorocinnamic acid by a consortium of Arthrobacter
      and Ralstonia strains.
AB  - Arthrobacter sp. strain G1 is able to grow on 4-fluorocinnamic acid (4-FCA) as
      sole carbon source. The organism converts 4-FCA into 4-fluorobenzoic acid (4-FBA)
      and utilizes the two-carbon side-chain for growth with some formation of 4
      fluoroacetophenone as a dead-end side product. We also have isolated Ralstonia
      sp. strain H1, an organism that degrades 4-FBA. A consortium of strains G1 and H1
      degraded 4-FCA with Monod kinetics during growth in batch and continuous
      cultures. Specific growth rates of strain G1 and specific degradation rates of 4
      FCA were observed to follow substrate inhibition kinetics, which could be modeled
      using the kinetic models of Haldane-Andrew and Luong-Levenspiel. The mixed
      culture showed complete mineralization of 4-FCA with quantitative release of
      fluoride, both in batch and continuous cultures. Steady-state chemostat cultures
      that were exposed to shock loadings of substrate responded with rapid degradation
      and returned to steady-state in 10-15 h, indicating that the mixed culture
      provided a robust system for continuous 4-FCA degradation.

PMID- 21728016
TI  - Revascularization for unprotected left main coronary artery disease: an evolution
      in clinical decision making.
AB  - Coronary artery bypass grafting (CABG) has been considered the standard therapy
      for unprotected (nonrevascularized) left main coronary disease (ULM). However,
      increasing experience with ULM percutaneous coronary intervention (PCI) has
      resulted in high procedural success and favorable early and late clinical
      outcomes. In particular, reduction in clinical restenosis with drug-eluting
      stents, evolution of procedural technique, and demonstration of favorable
      outcomes from comparative trials with CABG have promoted consideration of PCI as
      an alternative revascularization strategy in selected patients with ULM disease.
      This review summarizes the results from comparative studies examining PCI versus
      CABG for ULM disease, discusses changing indications for ULM PCI and identifies
      outstanding issues that must be considered before further advancing treatment
      recommendations.

PMID- 21728017
TI  - JAK inhibition in rheumatoid arthritis.

PMID- 21728018
TI  - Treatment of memory loss with herbal remedies.
AB  - OPINION STATEMENT: Increased rates of dementia throughout the world are creating
      an emergent need for successful preventive and treatment strategies. Despite a
      lack of any significant scientific basis, herbal remedies and other types of
      "complementary and alternative medicine" (CAM) are being aggressively marketed
      for both prophylactic and therapeutic effects in regard to memory disorders. In
      the past few years, a small number of controlled studies have explored the
      effectiveness of some of the more popular herbal and CAM remedies, including
      gingko biloba, phosphatidylcholine, phosphatidylserine, and omega-3 fatty acids.
      To date, the bulk of evidence suggests that such approaches are not successful in
      preventing or delaying cognitive decline or dementia, and there is little reason
      to prescribe these remedies for the treatment of established cognitive
      impairment. Some very preliminary evidence suggests that Gingko biloba may be
      useful in treating behavioral problems in demented people. It is likely that the
      absence of regulatory controls on the sale of herbal and CAM preparations will
      foster continued use of these agents and perhaps even accelerated use as the
      dementia epidemic increases, assuming no imminent breakthroughs in
      pharmacotherapy.

PMID- 21728019
TI  - Treating obstructive sleep apnea with positive pressure therapy.
AB  - OPINION STATEMENT: Obstructive sleep apnea (OSA), a highly prevalent disorder,
      has historically been under-recognized. As its diagnosis and recognition
      increases, physicians other than sleep specialists will need to gain familiarity
      with the management of this disorder, which is so closely tied to increased
      morbidity, mortality, and an overall health care burden. Most patients with OSA
      have been managed primarily with positive airway pressure, which is the focus of
      this review. The technology of positive airway pressure devices has advanced in
      order to improve adherence. For example, devices are now more compact and lighter
      in weight, less noisy, have heated humidification capability to diminish nasal
      dryness and congestion, have an increased variety of mask interfaces, and have
      modalities to minimize issues of pressure intolerance. In our practice, a
      multifaceted management model consisting of behavioral modification incorporating
      weight loss education, sleep hygiene education, and avoidance of exacerbating
      factors such as alcohol is usually employed in addition to positive airway
      pressure. A key component to effective treatment is close follow-up with
      troubleshooting if positive airway pressure adherence issues arise. Observance of
      early adherence issues is key, so that problems can be addressed sooner and long
      term compliance is assured. Also crucial in managing patients with OSA is
      education regarding potentially improved cardiovascular morbidity and mortality
      and better quality of life with improved alertness and less drowsy driving. Other
      therapies specific to OSA, such as oral appliances or upper airway surgery, are
      discussed as alternatives to positive airway pressure, but these are typically
      pursued only if the patient has a strong preference or if positive airway
      pressure therapy is unsuccessful. As current therapies improve and emerging
      therapies continue to develop into viable treatment strategies, the successful
      management of OSA will likely demonstrate further progress.

PMID- 21728020
TI  - Now you see it, now you don't?

PMID- 21728021
TI  - First case of posterior reversible encephalopathy syndrome associated with
      vinflunine.

PMID- 21728022
TI  - Novel dichlorophenyl urea compounds inhibit proliferation of human leukemia HL-60
      cells by inducing cell cycle arrest, differentiation and apoptosis.
AB  - Two novel dichlorophenyl urea compounds, SR4 and SR9, were synthesized in our
      laboratory and evaluated for anti-cancer activities. Specifically, we
      investigated the antiproliferative properties of these new compounds on
      promyelocytic HL-60 leukemia cells by analyzing their effects on cell
      differentiation, cell cycle progression and apoptosis. SR4 and SR9 were both
      cytotoxic to HL-60 cells in a dose-and time-dependent manner, with IC(50) of 1.2
      MUM and 2.2 MUM, respectively, after 72 h treatment. Both compounds strongly
      suppressed growth of HL-60 cells by promoting cell cycle arrest at the G0/G1
      transition, with concomitant decrease in protein levels of cyclins D1 and E2 and
      cyclin-dependent kinases (CDK 2 and CDK 4), and increased protein expression of
      CDK inhibitors p21(WAF1/Cip1) and p27(Kip1). In addition, either compounds induce
      cell differentiation as detected by increased NBT staining and expression of
      CD11b and CD14. Treatment with SR compounds also promoted mitochondrial-dependent
      apoptosis as confirmed by Annexin V-FITC double staining, DNA fragmentation,
      increased expression of caspase 3, 7 and 9, cytochrome c release, PARP
      degradation, and collapse in mitochondrial membrane potential (DeltaPsi(MT)).
      Collectively, these results provide evidence that SR4 and SR9 have the potential
      for the treatment of human leukemia and merit further investigation as
      therapeutic agents against other types of cancer.

PMID- 21728023
TI  - Phase II study of NK105, a paclitaxel-incorporating micellar nanoparticle, for
      previously treated advanced or recurrent gastric cancer.
AB  - PURPOSE: NK105 is a new drug delivery system formulation for paclitaxel (PTX)
      whose recommended dose (RD) is 150 mg PTX equivalent/m(2) administered every 3
      weeks, as determined in a phase I trial. This study aimed to evaluate the
      efficacy and safety of NK105 in patients with advanced gastric cancer after
      failure of first-line chemotherapy. EXPERIMENTAL DESIGN: Eligible patients had
      measurable disease and one chemotherapeutic regimen except taxane. NK105 (150 mg
      PTX equivalent/m(2)) was administered by a 30-minute intravenous infusion every 3
      weeks without anti-allergic premedication until disease progression, unacceptable
      toxicity or patient refusal. The primary efficacy endpoint was best overall
      response rate (ORR) post baseline. The secondary endpoints were progression-free
      survival (PFS), time to treatment failure (TTF) and overall survival (OS). All
      adverse events were reported using CTCAE v3.0. RESULTS: Between November 2007 and
      July 2009, 57 patients were enrolled and 56 were evaluable for efficacy. Two
      complete responses and 12 partial responses were observed for an ORR of 25%. The
      median PFS was 3.0 months, the median TTF was 2.8 months, and the median OS was
      14.4 months. Drug related toxicity was mainly mild (grades 1-2) to severe (grades
      3-4); other data: neutropenia (64.9%); leukopenia (17.5%); lymphopenia (8.8%);
      neuropathy-sensory (1.8%); fatigue (3.5%); and stomatitis (1.8%). There were no
      treatment-related deaths. CONCLUSIONS: This study of NK105 (150 mg PTX
      equivalent/m(2)) proves the concept for the modest activity and tolerability of a
      new drug delivery system formulation for PTX. A phase III trial will be evaluated
      to clarify survival benefit.

PMID- 21728024
TI  - The emerging role of interleukin-1beta in autoinflammatory diseases.
AB  - The autoinflammatory syndromes are a group of multisystem disorders characterized
      by recurrent episodes of fever and systemic inflammation affecting the eyes,
      joints, skin, and serosal surfaces in the absence of an immune reaction. Recent
      advances have revealed the importance of interleukin-1beta, not only in the
      pathogenesis of many of these rare inherited diseases, but also in acquired
      diseases. The development and availability of anti-interleukin-1beta therapeutics
      have introduced the possibility of proof-of-concept studies, which are likely to
      further widen this field.

PMID- 21728025
TI  - Relatively high-substrate consistency hydrolysis of steam-pretreated sweet
      sorghum bagasse at relatively low cellulase loading.
AB  - Sweet sorghum bagasse (SSB) was steam pretreated in the conditions of 190 
      degrees C for 5 min to assess its amenability to the pretreatment and enzymatic
      hydrolysis. Results showed that pretreatment conditions were robust enough to
      pretreat SSB with maximum of 87% glucan and 72% xylan recovery. Subsequent
      enzymatic hydrolysis showed that the pretreated SSB at 2% substrate consistency
      resulted in maximum of 70% glucan-glucose conversion. Increasing substrate
      consistency from 2% to 16% led to a significant reduction in glucan conversion.
      However, the decrease ratio of glucan-glucose conversion was the minimum when the
      consistency increased from 2% to 12%. When the pretreated SSB consistency of 12%
      was applied for hydrolysis, increase in cellulase loading from 7.5 up to 20
      filter paper units (FPU)/g glucan resulted only in 14% increase in glucan-glucose
      conversion compared to 20% increase with cellulase loading varying from 2.5 to
      7.5 FPU/g glucan. More than 10 cellobiase units (CBU)/g glucan beta-glucosidase
      supplementation had no noticeable improvement on glucan-glucose conversion.
      Additionally, supplementation of xylanase was found to significantly increase
      glucan-glucose conversion from 50% to 80% with the substrate consistency of 12%,
      when the cellulase and beta-glucosidase loadings were at relatively low enzyme
      loadings (7.5 FPU/g and 10 CBU/g glucan). It appeared that residual xylan played
      a critical role in hindering the ease of hydrolysis of SSB. A proper xylanase
      addition was suggested to achieve a high hydrolysis yield at relatively high
      substrate consistency with relatively low enzyme loadings.

PMID- 21728026
TI  - Plasma-assisted pretreatment of wheat straw for ethanol production.
AB  - The potential of wheat straw for ethanol production after pretreatment with O(3)
      generated in a plasma at atmospheric pressure and room temperature followed by
      fermentation was investigated. We found that cellulose and hemicellulose remained
      unaltered after ozonisation and a subsequent washing step, while lignin was
      degraded up to 95% by O(3). The loss of biomass after washing could be explained
      by the amount of lignin degraded. The washing water of pretreated samples (0-7 h)
      was analyzed for potential fermentation inhibitors. Approximately 30 lignin
      degradation products and a number of simple carboxylic acids and phenolic
      compounds were found, e.g., vanillic acid, acetic acid, and formic acid. Some
      components had the highest concentration at the beginning of the ozonisation
      process (0.5, 1 h), e.g., 4-hydroxybenzladehyde, while the concentration of
      others increased during the entire pretreatment (0-7 h), e.g., oxalic acid and
      acetovanillon. Interestingly, washing had no effect on the ethanol production
      with pretreatment times up to 1 h. Washing improved the glucose availability with
      pretreatment times of more than 2 h. One hour of ozonisation was found to be
      optimal for the use of washed and unwashed wheat straw for ethanol production
      (maximum ethanol yield, 52%). O(3) cost estimations were made for the production
      of ethanol at standard conditions.

PMID- 21728027
TI  - Improving the thermostability of a methyl parathion hydrolase by adding the ionic
      bond on protein surface.
AB  - The thermostability of the methyl parathion hydrolase (MPH_OCH) from Ochrobactrum
      sp. M231 was improved using site-directed mutagenesis. Two prolines (Pro76 and
      Pro78) located on the protein surface were selected for mutations after
      inspection of the sequence alignment of MPH_OCH and OPHC2, a thermostable
      organophosphorus hydrolase from Pseudomonas pseudoalcaligenes C2-1. The
      temperature of the double-point mutant (P76D/P78K) at which the mutant lost 50%
      of its activity (T50) was approximately 68  degrees C, which is higher than that
      of WT enzyme (64  degrees C), P76D (67  degrees C), and P78K (59  degrees C).
      Structural analysis of P76D/P78K indicated that the substituted residues (Asp76
      and Lys78) could generate an ionic bond and increase the structural electrostatic
      energy, which could then increase the stability of the protein. These results
      also suggest that the thermal stability of proteins could be improved by adding
      the ionic bond on protein surface.

PMID- 21728028
TI  - Differential proteins of the optic ganglion in octopus vulgaris under methanol
      stress revealed using proteomics.
AB  - An analytical approach using the two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) technique separated the proteome from the optic ganglia
      of Octopus vulgaris (OVOG). Approximately 600 protein spots were detected from
      the extraction when applying 150 MUg protein to a 2D-PAGE gel in the pH range 5.0
      8.0. Compared to the control, significant changes of 18 protein spots were
      observed in OVOG under the stress of native seawater containing 2% methanol for
      72 h. Among these spots, we found that eight were down-regulated and ten were up
      regulated in the gels, which were further identified using both peptide mass
      fingerprinting and database searches. Significant proteins such as glyceraldehyde
      3-phosphate dehydrogenase, alpha subunit of succinyl-CoA synthetase, alcohol
      dehydrogenase, and long-chain specific acyl-CoA dehydrogenase were up-regulated
      proteins, whereas putative ABC transporter was a down -regulated protein. These
      differential proteins at the level of subcellular localization were further
      classified using LOCtree software with a hierarchical system of support vector
      machines. We found that most of the differential proteins in the gel could be
      identified as mitochondrial proteins, suggesting that these protective or marker
      proteins might help to prevent methanol poisoning via the mitochondria in the
      optical ganglia. The results indicated that both beta-tubulin and beta-actin were
      potential biomarkers as up-regulated proteins for monitoring methanol toxicosis
      associated with fish foods such as octopus and shark.

PMID- 21728029
TI  - Isolation, characterization, and catalytic properties of a novel lipase which is
      activated in ionic liquids and organic solvents.
AB  - A novel extracellular lipase with organic solvent tolerance was isolated from a
      local Pseudomonas species. The lipase gene was cloned and expressed in
      Escherichia coli as a heterologous host and purified by affinity chromatography.
      The activity of purified lipase was investigated in the presence of imidazolium
      based ionic liquids (ILs) such as EMIM[Cl], BMIM[Cl], and HMIM[Cl]. It has been
      found that the activity of treated lipase with ILs was higher than untreated
      control in the hydrolysis reaction. Also, the results indicated that the
      enzymatic activity strongly depends on IL concentration in reaction media. The
      best concentration of the IL was 30%, 45%, and 50% (v/v) for HMIM[Cl], BMIM[Cl],
      and EMIM[Cl], respectively. Additionally, the enzyme exhibited excellent
      stability in the presence of 25% of n-hexane, toluene, acetone, and t-butanol.
      The optimum values of pH and temperature were determined 10 and 55  degrees C,
      respectively. The K (m) and V (max) values were calculated 0.4 mM and 1.92 U/ml,
      respectively, using p-nitrophenyl palmitate as substrate. With respect to the
      biochemical properties of the newly isolated lipase such as high-level stability
      and noticeable activity in the presence of organic solvents and ionic liquids,
      the newly isolated lipase seems to be a good candidate for environmental and
      industrial processes carried out in non-aqueous media.

PMID- 21728030
TI  - Recurrence rates and factors for recurrence after radiofrequency ablation
      combined with transarterial chemoembolization for hepatocellular carcinoma: a
      retrospective cohort study.
AB  - PURPOSE: There have been reports that radiofrequency ablation (RFA) combined with
      transarterial chemoembolization (TACE) is as equally effective as surgical
      resection for the treatment of hepatocellular carcinoma (HCC). This study aimed
      to evaluate recurrence rate and risk factor of recurrence after RFA combined with
      TACE for early stage HCC. METHODS: We reviewed the medical records of the
      patients who were diagnosed with early stage HCC between March 2006 and August
      2008 at Korea University Medical Center and treated with RFA combined with TACE
      for curative intent (n = 65). RESULTS: Recurrence rate was 40% (26 cases) and the
      time to recurrence was 14.9 months. Cumulative recurrence rate at 1 year was 20%
      (13 cases) and at 2 years was 33.8% (22 cases). Significant variables for
      recurrence were: (1) RFA repeated more than one session at initial therapy (P <
      0.001) and (2) size of main lesion >=2 cm (P = 0.047). CONCLUSIONS: The
      recurrence rate of combination therapy was considerably high. Regardless of the
      therapy used, careful post-RFA follow-up is needed, especially if additional
      treatment is required after the first session or if the main lesion is >=2 cm at
      the time of RFA.

PMID- 21728031
TI  - Development of a quantitative real-time nucleic acid sequence-based amplification
      assay with an internal control using molecular beacon probes for selective and
      sensitive detection of human rhinovirus serotypes.
AB  - Evidence demonstrating that human rhinovirus (HRV) disease is not exclusively
      limited to the upper airways and may cause lower respiratory complications,
      together with the frequency of HRV infections and the increasing number of
      immunocompromised patients underline the need for rapid and accurate diagnosis of
      HRV infections. In this study, we developed the first quantitative real-time
      nucleic acid sequence-based amplification assay with an internal control using
      molecular beacon probes for selective and sensitive detection of human rhinovirus
      serotypes. We described a simple method to accurately quantify RNA target by
      computing the time to positivity (TTP) values for HRV RNA. Quantification
      capacity was assessed by plotting these TTP values against the starting number of
      target molecules. By using this simple method, we have significantly increased
      the diagnostic accuracy, precision, and trueness of real-time NASBA assay.
      Specificity of the method was verified in both in silico and experimental
      studies. Moreover, for assessment of clinical reactivity of the assay, NASBA has
      been validated on bronchoalveolar lavage (BAL) specimens. Our quantitative NASBA
      assay was found to be very specific, accurate, and precise with high
      repeatability and reproducibility.

PMID- 21728032
TI  - Maternal relationship instability influences on children's emotional and
      behavioral functioning in low-income families.
AB  - The present study investigated associations between maternal relationship
      instability patterns and children's behavioral and emotional functioning in
      middle childhood in a representative sample of low-income urban families (N =
      891). Data from the Three-City Study tracked maternal partnerships through the
      child's life, assessing total marital and cohabiting relationship transitions and
      delineating transitions by developmental timing, and by directionality (i.e.,
      entrances into versus exits from partnerships). Analyses linking instability to
      child behaviors at age 8 found that a greater total number of maternal
      relationship transitions predicted higher anxious, somatic, and conduct problems,
      with recent transitions (in the prior 2 years) driving these results.
      Consideration of partnership formations versus dissolutions indicated that recent
      entrances into new partnerships, and entrances into cohabitations, were most
      consistently associated with problematic functioning across numerous aspects of
      children's emotional and behavioral functioning. Policy implications of these
      findings are discussed.

PMID- 21728033
TI  - Immunosuppressive effects of opioids--clinical relevance.
AB  - Opioid-induced immunosuppression has been demonstrated in cell culture
      experiments and in animal models. This is in striking contrast to the paucity of
      confirmatory studies in humans. This review describes the basic pharmacokinetics
      and -dynamics of opioid use in patients. It summarizes the major findings on
      opioid use and infectious complications in intensive care unit (ICU) patients, in
      patients with acute or chronic non-malignant pain, and in intravenous drug users
      (IDU). The limitations of studies in each area are discussed. For example,
      ethical concerns may complicate randomized placebo-controlled trials (RCT) in
      acute postoperative pain and for a large part of ICU patients. Importantly, most
      studies in patients with chronic (non-malignant) pain only inadequately report
      infectious complications in relation to opioid use since their incidence is
      usually not considered to be drug related. Infectious complications in IDUs are
      very frequent but cannot easily be distinguished from risk behavior or risk
      environment. In summary, convincing clinical evidence is lacking that opioids per
      se increase the rate of infectious complications in most patient categories. From
      a clinical standpoint, important unresolved issues are i) selection of relevant
      animal models, ii) opioid selection and discontinuation, and iii) the role of
      coexisting diseases and concomitant other medications.

PMID- 21728036
TI  - Regional assessment of groundwater quality for drinking purpose.
AB  - Owing to limited surface water during a long-term drought, this work attempted to
      locate clean and safe groundwater in the Choushui River alluvial fan of Taiwan
      based on drinking-water quality standards. Because aquifers contained several
      pollutants, multivariate indicator kriging (MVIK) was adopted to integrate the
      multiple pollutants in groundwater based on drinking- and raw-water quality
      standards and to explore spatial uncertainty. According to probabilities
      estimated by MVIK, safe zones were determined under four treatment conditions--no
      treatment; ammonium-N and iron removal; manganese and arsenic removal; and
      ammonium-N, iron, manganese, and arsenic removal. The analyzed results reveal
      that groundwater in the study area is not appropriate for drinking use without
      any treatments because of high ammonium-N, iron, manganese, and/or arsenic
      concentrations. After ammonium-N, iron, manganese, and arsenic removed, about
      81.9-94.9% of total areas can extract safe groundwater for drinking. The proximal
      fan, central mid-fan, southern mid-fan, and northern regions are the excellent
      locations to pump safe groundwater for drinking after treatment. Deep aquifers of
      exceeding 200 m depth have wider regions to obtain excellent groundwater than
      shallow aquifers do.

PMID- 21728037
TI  - Active methanotrophs in two contrasting North American peatland ecosystems
      revealed using DNA-SIP.
AB  - The active methanotroph community was investigated in two contrasting North
      American peatlands, a nutrient-rich sedge fen and nutrient-poor Sphagnum bog
      using in vitro incubations and (13)C-DNA stable-isotope probing (SIP) to measure
      methane (CH(4)) oxidation rates and label active microbes followed by
      fingerprinting and sequencing of bacterial and archaeal 16S rDNA and methane
      monooxygenase (pmoA and mmoX) genes. Rates of CH(4) oxidation were slightly, but
      significantly, faster in the bog and methanotrophs belonged to the class
      Alphaproteobacteria and were similar to other methanotrophs of the genera
      Methylocystis, Methylosinus, and Methylocapsa or Methylocella detected in, or
      isolated from, European bogs. The fen had a greater phylogenetic diversity of
      organisms that had assimilated (13)C, including methanotrophs from both the Alpha
      and Gammaproteobacteria classes and other potentially non-methanotrophic
      organisms that were similar to bacteria detected in a UK and Finnish fen. Based
      on similarities between bacteria in our sites and those in Europe, including
      Russia, we conclude that site physicochemical characteristics rather than
      biogeography controlled the phylogenetic diversity of active methanotrophs and
      that differences in phylogenetic diversity between the bog and fen did not relate
      to measured CH(4) oxidation rates. A single crenarchaeon in the bog site appeared
      to be assimilating (13)C in 16S rDNA; however, its phylogenetic similarity to
      other CO(2)-utilizing archaea probably indicates that this organism is not
      directly involved in CH(4) oxidation in peat.

PMID- 21728035
TI  - Tumor necrosis factor-alpha and the roles it plays in homeostatic and
      degenerative processes within the central nervous system.
AB  - Tumor Necrosis Factor-alpha (TNF-alpha) is a prototypic pro-inflammatory cytokine
      involved in the innate immune response. TNF-alpha ligation and downstream
      signaling with one of its cognate receptors, TNF-RI or TNF-RII, modulates
      fundamental processes in the brain including synapse formation and regulation,
      neurogenesis, regeneration, and general maintenance of the central nervous system
      (CNS). During states of chronic neuroinflammation, extensive experimental
      evidence implicates TNF-alpha as a key mediator in disease progression, gliosis,
      demyelination, inflammation, blood-brain-barrier deterioration, and cell death.
      This review explores the complex roles of TNF-alpha in the CNS under normal
      physiologic conditions and during neurodegeneration. We focus our discussion on
      Multiple Sclerosis, Parkinson's disease, and Alzheimer's disease, relaying the
      outcomes of preclinical and clinical testing of TNF-alpha directed therapeutic
      strategies, and arguing that despite the wealth of functions attributed to this
      central cytokine, surprisingly little is known about the cell type- and stage
      specific roles of TNF-alpha in these debilitating disorders.

PMID- 21728034
TI  - Methamphetamine-associated psychosis.
AB  - Methamphetamine (METH) is a frequent drug of abuse in U.S. populations and
      commonly associated with psychosis. This may be a factor in frequent criminal
      justice referrals and lengthy treatment required by METH users. Persecutory
      delusions and auditory hallucinations are the most consistent symptoms of METH
      associated psychosis (MAP). MAP has largely been studied in Asian populations and
      risk factors have varied across studies. Duration, frequency and amount of use as
      well as sexual abuse, family history, other substance use, and co-occurring
      personality and mood disorders are risk factors for MAP. MAP may be unique with
      its long duration of psychosis and recurrence without relapse to METH. Seven
      candidate genes have been identified that may be associated with MAP. Six of
      these genes are also associated with susceptibility, symptoms, or treatment of
      schizophrenia and most are linked to glutamatergic neurotransmission. Animal
      studies of pre-pulse inhibition, attenuation of social interaction, and
      stereotypy and alterations in locomotion are used to study MAP in rodents.
      Employing various models, rodent studies have identified neuroanatomical and
      neurochemical changes associated with METH use. Throughout this review, we
      identify key gaps in our understanding of MAP and suggest potential directions
      for future research.

PMID- 21728038
TI  - Phylogenetic diversity of bacteria associated with the marine sponge Gelliodes
      carnosa collected from the Hainan Island coastal waters of the South China Sea.
AB  - Several molecular techniques were employed to document the bacterial diversity
      associated with the marine sponge Gelliodes carnosa. Cultivation-dependent and
      cultivation-independent methods were used to obtain the 16S rRNA gene sequences
      of the bacteria. Phylogenetic analysis based on the 16S rRNA gene sequences
      showed that the bacterial community structure was highly diverse with
      representatives of the high G + C Gram-positive bacteria, cyanobacteria, low G +
      C Gram-positive bacteria, and proteobacteria (alpha-, beta-, and gamma-), most of
      which were also found in other marine environments, including in association with
      other sponges. Overall, 300 bacterial isolates were cultivated, and a total of 62
      operational taxonomic units (OTUs) were identified from these isolates by
      restriction fragment length polymorphism (RFLP) analysis and DNA sequencing of
      the 16S rRNA genes. Approximately 1,000 16S rRNA gene clones were obtained by the
      cultivation-independent method. A total of 310 clones were randomly selected for
      RFLP analysis, from which 33 OTUs were acquired by further DNA sequencing and
      chimera checking. A total of 12 cultured OTUs (19.4% of the total cultured OTUs)
      and 13 uncultured OTUs (39.4% of the total uncultured OTUs) had low sequence
      identity (<=97%) with their closest matches in GenBank and were probably new
      species. Our data provide strong evidence for the presence of a diverse variety
      of unidentified bacteria in the marine sponge G. carnosa. A relatively high
      proportion of the isolates exhibited antimicrobial activity, and the deferred
      antagonism assay showed that over half of the active isolates exhibited a much
      stronger bioactivity when grown on medium containing seawater. In addition to
      demonstrating that the sponge-associated bacteria could be a rich source of new
      biologically active natural products, the results may have ecological
      implications. This study expands our knowledge of the diversity of sponge
      associated bacteria and contributes to the growing database of the bacterial
      communities within sponges.

PMID- 21728039
TI  - A new insight into allelopathic effects of Alexandrium minutum on photosynthesis
      and respiration of the diatom Chaetoceros neogracile revealed by photosynthetic
      performance analysis and flow cytometry.
AB  - The allelopathic effects of Alexandrium minutum, a toxic dinoflagellate, on the
      diatom Chaetoceros neogracile were evaluated using unialgal cultures evaluated by
      flow cytometry (FCM) and photosynthetic-performance analysis. Using FCM, we
      demonstrated that red chlorophyll fluorescence, relative cell size (Forward
      scatter of blue laser light, FSC) and cell complexity (Side scatter, 90 degrees 
      angle scatter of blue laser light, SSC) significantly and rapidly decreased in C.
      neogracile cells exposed to A. minutum. Cells of C. neogracile exposed to A.
      minutum had fewer active photosynthetic reaction centers and sharply decreased
      photosynthetic efficiency. These effects were intensified with advancing A.
      minutum batch culture age and cell density. The supernatant of A. minutum
      contained the majority of the putative allelopathic compounds, and the biological
      activity of these compounds remained active less than 9 h after release. This
      paper describes for the first time specific effects of allelochemicals produced
      by A. minutum on the photosynthetic apparatus of microalgal target cells. The
      biochemical composition of A. minutum allelopathic agents, however, remains
      unknown and still needs to be investigated.

PMID- 21728040
TI  - Olfactory sulcal depth and olfactory bulb volume in patients with schizophrenia:
      an MRI study.
AB  - The current report used structural magnetic resonance imaging (MRI) to
      objectively measure olfactory bulb volume and olfactory sulcal depth in patients
      diagnosed with chronic schizophrenia and healthy controls. Additional measures
      were obtained to assess olfactory function. The olfactory bulb and sulcus were
      manually traced on structural 3T MRIs for 25 right-handed male patients diagnosed
      with chronic schizophrenia and 25 matched male healthy controls. A sub-set of
      subjects received the University of Pennsylvania Smell Identification Test
      (UPSIT). Olfactory bulb volume was significantly decreased in patients with
      schizophrenia compared to healthy controls, as was their performance on the
      UPSIT. Additionally, a positive correlation was seen in patients between right
      bulb volume and UPSIT scores. Overall, our findings support earlier research
      studies showing morphometric and functional changes in the olfactory system in
      patients with schizophrenia.

PMID- 21728041
TI  - Oxidative damage of lysozyme and human serum albumin and their mixtures: a
      comparison of photosensitized and peroxyl radical promoted processes.
AB  - Oxidative modifications of lysozyme (Lyso) and human serum albumin (HSA) mediated
      by photoinduced processes and peroxyl radicals were studied. Both oxidative
      conditions were applied to the separate proteins and their mixtures. Dimerization
      and fragmentation of the proteins do not correlate with the formation of
      carbonyls or peroxides, implying that evaluation of these changes is not an index
      of the overall oxidative modification of a protein. The results obtained also
      show that the hypothesis that the electrostatic interactions of Lyso and HSA
      could facilitate the formation of Lyso-HSA dimers in the presence of a source of
      reactive oxygen species was verified in both ROS-producing systems.

PMID- 21728042
TI  - MicroRNAs as regulators of neural stem cell-related pathways in glioblastoma
      multiforme.
AB  - MicroRNAs are endogenous non-coding small RNAs that have been described as highly
      conserved regulators of gene expression. They are involved in cancer and in the
      regulation of neural development and stem cell function. Recent studies suggest
      that a small subpopulation of cancer stem cells (CSCs) has the capacity to
      repopulate solid tumours such as glioblastoma (GBM), drive malignant progression
      and mediate radio- and chemoresistance. GBM-derived CSCs share the fundamental
      stem cell properties of self-renewal and multipotency with neural stem cells
      (NSCs) and may be regulated by miRNAs. In this review, we will summarize the
      current knowledge regarding the role of miRNAs in GBM development with a focus on
      the regulation of GBM-CSCs. We propose a list of miRNAs that could serve as
      molecular classifiers for GBMs and/or as promising therapeutic targets for such
      brain tumours.

PMID- 21728043
TI  - Potentiation of regulatory volume decrease by a p2-like receptor and arachidonic
      acid in american alligator erythrocytes.
AB  - This study examined the role of a P2 receptor and arachidonic acid (AA) in
      regulatory volume decrease (RVD) by American alligator red blood cells (RBCs).
      Osmotic fragility was determined optically, mean cell volume was measured by
      electronic sizing, and changes in intracellular Ca(2+) concentration were
      visualized using fluorescence microscopy. Gadolinium (50 MUM), hexokinase (2.5
      U/ml), and suramin (100 MUM) increased osmotic fragility, blocked volume recovery
      after hypotonic shock, and prevented a rise in intracellular Ca(2+) that normally
      occurs during cell swelling. The P2X antagonists PPADS (50 MUM) and TNP-ATP (10
      MUM) also increased fragility and inhibited volume recovery. In contrast,
      ATPgammaS (10 MUM), alpha,beta-methylene-ATP (50 MUM) and Bz-ATP (50 MUM) had the
      opposite effect, whereas 2-methylthio-ATP (50 MUM) and UTP (10 MUM) had no
      effect. In addition, the phospholipase A(2) (PLA(2)) inhibitors ONO-RS-082 (10
      MUM), chlorpromazine (10 MUM), and isotetrandrine (10 MUM) increased osmotic
      fragility and blocked volume recovery, whereas AA (10 MUM) and its
      nonhydrolyzable analog eicosatetraynoic acid (ETYA, 10 MUM) had the reverse
      effect. Further, AA (10 MUM), but not ATPgammaS (10 MUM), prevented the
      inhibitory effect of a low Ca(2+)-EGTA Ringer on RVD, whereas both AA (10 MUM)
      and ATPgammaS (10 MUM) caused cell shrinkage under isosmotic conditions. In
      conclusion, our results are consistent with the presence of a P2-like receptor
      whose activation stimulated RVD. In addition, AA also was important for volume
      recovery.

PMID- 21728045
TI  - [Retraction Note: Pathophysiology and pathogens of sepsis.]

PMID- 21728046
TI  - Molybdenum-99/technetium-99m management: race against time.
AB  - Molybdenum-99 is a parent of diagnostic nuclear medicine. It decays to technetium
      99m, which used in over 30 million investigations per year around the world.
      Supplies of Tc-99m remained fragile in the last few years, which may occur again
      in the short and long term. Few suggestions have been registered in this letter
      to cope inadequate supply of the most wanted radionuclide for patient care.

PMID- 21728044
TI  - The life and death of breast cancer cells: proposing a role for the effects of
      phytoestrogens on potassium channels.
AB  - Changes in the regulation of potassium channels are increasingly implicated in
      the altered activity of breast cancer cells. Increased or reduced expression of a
      number of K(+) channels have been identified in numerous breast cancer cell lines
      and cancerous tissue biopsy samples, compared to normal tissue, and are
      associated with tumor formation and spread, enhanced levels of proliferation, and
      resistance to apoptotic stimuli. Through knockout or silencing of K(+) channel
      genes, and use of specific or more broad pharmacologic K(+) channel blockers, the
      growth of numerous cell lines, including breast cancer cells, has been modified.
      In this manner it has been proposed that in MCF7 breast cancer cells
      proliferation appears to be regulated by the activity of a number of K(+)
      channels, including the Ca(2+) activated K(+) channels, and the voltage-gated
      K(+) channels hEAG and K(v)1.1. The effect of phytoestrogens on K(+) channels has
      not been extensively studied but yields some interesting results. In a number of
      cell lines the phytoestrogen genistein inhibits K(+) current through several
      channels including K(v)1.3 and hERG. Where it has been used, structurally similar
      daidzein has little or no effect on K(+) channel activity. Since many K(+)
      channels have roles in proliferation and apoptosis in breast cancer cells, the
      impact of K(+) channel regulation by phytoestrogens is of potentially great
      relevance.

PMID- 21728047
TI  - [Uncooperative children during induction of anesthesia : theory and practice].
AB  - Perioperative anxiety and the resulting lack of cooperation during induction of
      anesthesia is a common problem in pediatric anesthesia. The extent of anxiety
      depends on a variety of factors concerning the child, the parents, the anesthesia
      team and the hospital's friendly atmosphere and infrastructure. Apart from
      premedication there are a number of non-pharmacological means to improve the
      child's cooperation and thereby facilitate the induction of anesthesia. If the
      child is still uncooperative despite an optimal preparation, the anesthetist has
      to decide whether to postpone the operation or to perform induction of anesthesia
      under physical restraint in consideration of various criteria.

PMID- 21728048
TI  - [Silexan and narcosis : case report and possibilities of preoperative and
      perioperative management].
AB  - The increased use of phytotherapeutic drugs means that anesthetists are more
      often confronted with these drugs. In this case report possible problems which
      can occur are demonstrated exemplified by silexan. Silexan is a phytotherapeutic
      anxiolytic which is used in anxiety disorders. Because of its potential mechanism
      of action via the neurotransmitter gamma-aminobutyric acid (GABA) receptors
      interactions with narcotic drugs are possible. The case of an 18-year-old girl
      who underwent an operation under general anesthesia while taking silexan as long
      term medication is presented. The desired depth of narcosis could only be reached
      by inhalative induction with sevoflurane after unsuccessful induction attempts
      using intravenous propofol and thiopental. Possible explanations for this route
      and inhalative induction as a possible alternative are discussed.

PMID- 21728049
TI  - [Severe airway distress following cervical spine operation: retrospective
      breakdown of the chain of errors].
AB  - A 71-year-old female patient received a prothesis due to a cervical disc
      prolapsed and bleeding into the collar soft tissues occurred postoperatively.
      Following a computed tomography examination severe peracute respiratory
      decompensation occurred while administering topical anesthesia to the pharynx in
      order to perform fiber optic intubation. Endotracheal intubation using
      conventional laryngoscopy was unsuccessful and the patient required immediate
      cricothyroidotomy. As an on-site cricothyrotomy set to establish a secure airway
      was not available the decision was taken to perform surgical cricothyroidotomy.
      As a conclusion to this life-threatening event in the case of symptoms, such as
      dyspnea, dysphonia and dysphagia after operations of the cervical spine the
      airway has to be secured early and according to the local algorithm.

PMID- 21728050
TI  - [Fluorescein aspiration during induction of anaesthesia : complication preceding
      surgical treatment of cerebrospinal fluid fistula].
AB  - This case history deals with an 85-year-old patient who underwent surgery to
      treat rhinoliquorrhea. The patient aspirated a lutescent fluid shortly after
      anesthesia was administered. However, this fluid was not gastric juice but
      cerebrospinal fluid (CSF) running down the nasopharynx. The CSF had been stained
      with fluorescein prior to surgery in order to help localize the CSF fistula. This
      case of top down aspiration is discussed and preventive measures which can be
      employed in order to avoid similar complications in patients with rhinoliquorrhea
      are presented.

PMID- 21728051
TI  - A Halsted mastectomy 21 years before Halsted.

PMID- 21728052
TI  - COX-2 expression predicts worse breast cancer prognosis and does not modify the
      association with aspirin.
AB  - Some previous studies have found worse prognosis among cyclooxygenase-2 (COX-2)
      expressing breast cancers. Aspirin and NSAIDs inhibit COX-2. Three studies,
      including ours, have reported a survival advantage among women with breast cancer
      who take either aspirin or NSAIDs. Through this study we hypothesized that in the
      Nurses' Health Study (NHS), COX-2 expression would be associated with worse
      prognosis, and aspirin use would be associated with better survival particularly
      among women with COX-2 positive tumors. In this study we investigated 2,001 women
      presenting with invasive breast cancers stained for COX-2 by
      immunohistochemistry. Tumor prognostic factors were from medical records. Aspirin
      use was assessed at least 12 months after diagnosis and updated. Cause of death
      was identified from death certificates. Statistical analyses included logistic
      regression of prognostic factors with COX-2 status as the outcome, and
      proportional hazards regression with breast cancer death as the outcome. Tumor
      COX-2 expression was associated with higher diagnostic stage. Compared with stage
      I, the RR(95% CI) for stages II-IV were 1.16 (0.93-1.45), 1.68 (1.27-2.22), and
      1.76 (0.93-3.32). COX-2 expression was associated with lobular compared with
      ductal histology (1.40 [1.02-1.92]), and estrogen receptor positive compared with
      negative (2.22 [1.66-2.95]). The RR(95% CI) of breast cancer death for current
      aspirin use was similar for women with COX-2-positive and COX-2-negative tumors;
      0.64 (0.43-0.96) and 0.57 (0.44-0.74), respectively. In the NHS, COX-2 breast
      cancer expression was associated with higher stage at diagnosis. The survival
      benefit associated with aspirin use did not differ by COX-2 status. COX-2 breast
      cancer expression is associated with worse prognosis. If aspirin truly impacts
      breast cancer survival, then it is not solely via COX-2.

PMID- 21728053
TI  - Demand feeding and welfare in farmed fish.
AB  - Following the development of demand-feeding systems, many experiments have been
      conducted to explore feeding motivation and feed intake in farmed fish. This work
      aims to review a selection of studies in the field, focusing on three key
      factors, related to demand feeding and fish welfare. Firstly, we outline how
      demand feeders should be considered when developing feed management strategies
      for improving welfare in production conditions. Secondly, via laboratory demand
      feeding experiments, we show self-feeding activities depend not only on feeding
      motivation and social organisation, but also on individual learning capacity and
      risk-taking behaviour. Thirdly, we report encouraging results demonstrating that
      when presented with two or more self-feeders containing complementary foods, fish
      select a diet according to their specific nutritional requirements, suggesting
      that demand feeders could be used to improve welfare by allowing fish to meet
      their nutritional needs.

PMID- 21728054
TI  - Temperature and dietary starch level affected protein but not starch
      digestibility in gilthead sea bream juveniles.
AB  - A study was carried out with gilthead sea bream juveniles to assess the effect of
      water temperature (18 and 25 degrees C) and dietary pregelatinized starch level
      (10, 20 and 30%) on digestibility of protein and starch and on the activity of
      proteolytic and amylolytic enzymes. ADC of pregelatinized starch was very high
      (>99%) irrespectively of dietary inclusion level, and it was not affected by
      water temperature. ADC of protein was also high (>90%) but improved at the higher
      water temperature. Dietary starch interacted with protein digestibility, which
      decreased as dietary starch level increased. Temperature affected both acid and
      basic protease activities, with acid protease activity being higher at 25 degrees
      C and basic protease activity being higher at 18 degrees C. However, total
      proteolytic activity and amylase activities were not affected by water
      temperature. Dietary carbohydrate exerted no effect on proteolytic or amylolitic
      activities. It is concluded that gilthead sea bream juveniles digest
      pregelatinized starch very efficiently irrespective of water temperature, due to
      adjustments of amylase activity to cope with temperature differences.
      Pregelatinized starch interacts negatively with protein digestibility, with the 
      ADC of protein decreasing as dietary starch levels increase.

PMID- 21728055
TI  - Dietary calcium and magnesium intake in relation to cancer incidence and
      mortality in a German prospective cohort (EPIC-Heidelberg).
AB  - To prospectively evaluate the associations of dietary calcium and magnesium
      intake with cancer incidence and mortality, data of 24,323 participants of the
      Heidelberg cohort of the European Prospective Investigation into Cancer and
      Nutrition (EPIC-Heidelberg), who were aged 35-64 years and cancer-free at
      recruitment (1994-1998), were analyzed using multivariate Cox regression models.
      After an average follow-up time of 11 years, 2,050 incident cancers were
      diagnosed and 513 cancer deaths occurred. Dietary calcium intake was inversely
      but not statistically significantly associated with colorectal cancer risk
      (hazard ratio [HR] for per 100 mg increase in intake: 0.95; 95% confidence
      interval [CI]: 0.88, 1.02) and lung cancer risk (HR for per 100 mg increase in
      intake: 0.94; 95% CI: 0.87, 1.02). No statistically significant associations were
      observed between dietary calcium intake and site-specific or overall cancer
      incidence or mortality. Dietary magnesium intake was not statistically
      significantly associated with any of the investigated outcomes. This prospective
      cohort study provides no strong evidence to support that high dietary calcium and
      magnesium intake in the intake range observed in a German population may reduce
      cancer incidence or mortality.

PMID- 21728056
TI  - Prevalence and implications of multiple cancer screening needs among Hispanic
      community health center patients.
AB  - OBJECTIVES: To examine adherence rates for multiple cancer screening tests, which
      will inform prevention efforts in community health centers (CHCs). METHODS: We
      report on the prevalence of screening for multiple cancers (cervical, breast and
      colorectal) among 43,000 patients who are predominantly Hispanic, in four CHC
      sites that share an integrated electronic medical record. RESULTS: Among the
      20,057 patients eligible for at least one test, 43% of the population was current
      on all screening targets; 15,887 additional screening tests were needed among
      11,526 individuals. CONCLUSIONS: Expanding use of health information technology
      in community health centers provides an opportunity to create an electronic
      infrastructure for addressing multiple screening needs from a patient-centered
      perspective.

PMID- 21728057
TI  - Adoption of anesthesia information management systems by US anesthesiologists.
AB  - OBJECTIVE: Electronic medical records (EMR) may increase the safety and
      efficiency of healthcare. Anesthesia care is a significant component of the
      perioperative period, yet little is known about the adoption of anesthesia
      information management systems (AIMS) by US anesthesiologists, particularly in
      non-academic settings. Herein, we report the results of a survey of US
      anesthesiologists regarding adoption of AIMS and anesthesiologist-perceived
      advantages and barriers to AIMS adoption. METHODS: Using the e-mail database of
      the American Society of Anesthesiologists, we solicited randomly selected US
      anesthesiologists to participate in a survey of their AIMS adoption, perceived
      advantages and barriers to AIMS. Two and then 3 weeks after the initial mailing,
      a follow-up e-mail was sent to each anesthesiologist. The study was closed 4
      weeks after the initial mailing. RESULTS: Five thousand anesthesiologists were
      solicited; 615 (12.3%) responses were received. Twenty-four percent of
      respondents had installed an AIMS, while 13% were either installing a system now
      or had selected one, and an additional 13% were actively searching. Larger
      anesthesiology groups with large case loads, urban settings, and government
      affiliated or academic institutions were more likely to have adopted AIMS.
      Initial cost was the most frequently cited AIMS barrier. The most commonly cited
      benefit was more accurate clinical documentation (79%), while unanticipated need
      for ongoing information technology support (49%) and difficult integration of
      AIMS with an existing EMR (61%) were the most commonly cited problems. There were
      no barriers cited significantly more often by non-adopters than adopters.
      CONCLUSIONS: At least 50% of our survey respondents were currently using,
      installing, planning to install, or searching for an AIMS. However, the strength
      of any conclusion is undermined by a low survey response rate and potential bias
      as respondents using or searching for an AIMS may be more likely to participate.
      Nonetheless, challenges exist for anesthesiologists considering AIMS adoption
      including cost. Furthermore, important questions remain regarding payment for
      anesthesia services and the relationship of AIMS and "meaningful use" as defined
      by the Centers for Medicare & Medicaid Services.

PMID- 21728058
TI  - Ixodid ticks of road-killed wildlife species in southern Italy: new tick-host
      associations and locality records.
AB  - The present study aimed to identify ticks collected from road-killed wildlife
      species retrieved in several localities of southern Italy and to assess the
      presence of Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum and
      Rickettsia spp. DNA in ticks. Collections were carried out from January 2000 to
      December 2009 on wild animals found dead within the territories of 11
      municipalities from three regions (i.e., Apulia, Basilicata, and Calabria). In
      total, 189 carcasses of wild animals belonging to 10 species were checked for
      tick infestation, and 40 animals belonging to seven species were found
      parasitized. One hundred and twenty-five ixodid ticks (11 larvae, 14 nymphs, 77
      males, and 23 females) were collected and identified as belonging to nine
      species, namely Dermacentor marginatus, Haemaphysalis erinacei, Hyalomma
      marginatum, Ixodes acuminatus, Ixodes canisuga, Ixodes hexagonus, Ixodes ricinus,
      Rhipicephalus bursa, and Rhipicephalus turanicus. None of the 36 tick specimens
      tested by PCR was positive for tick-borne pathogens. The results add new
      information on the tick fauna associated with wild animals in Italy, reporting
      new tick-host associations. Further field studies are still needed to ascertain
      the suitability of certain wildlife species as hosts for some tick species,
      particularly for those implicated in the transmission of pathogens to domestic
      animals and humans. Finally, from a conservation perspective, it would be
      interesting to assess whether these wild animals (e.g., Lepus corsicanus) are
      exposed to tick-borne pathogens, investigating the possible implications for
      their health and behavior.

PMID- 21728059
TI  - [Importance of sagittal balance of the spinal column : X-ray cosmetics or key to
      success?].

PMID- 21728060
TI  - An association study of the genetic polymorphisms in 13 neural plasticity-related
      genes with semantic and episodic memories.
AB  - Semantic and episodic memories were two different attributes of long-term memory.
      In the past few years, plenty of physiological evidence has indicated that neural
      plasticity is involved in the formation of long-term memory. In the present
      study, we hypothesized that some functional variants of neural plasticity-related
      genes were related to episodic and semantic memories. To confirm this hypothesis,
      we examined the relationship of 13 plasticity-related genes with episodic and
      semantic memories. The results indicated that there was a statistically
      significant difference in semantic memory scores among the three genotype groups
      of T267C in 5-HT ( 6 ) (chi (2) = 16.638, p = 0.0002). However, the functional
      variations in BDNF, COMT, DBH, DRD ( 2 ), DRD ( 3 ), DRD ( 4 ), MAOA, TPH ( 2 ),
      5-HT ( 2A ), GRM ( 1 ), and GRIN2B had no observable effects on the memories. Our
      preliminary results confirm the hypothesis that a small number of functional
      variants of the neural plasticity-related genes, such as T267C in 5-HT ( 6 ),
      play important roles in human specific memory.

PMID- 21728061
TI  - Effects of nitric oxide on the survival and neuritogenesis of cerebellar Purkinje
      neurons.
AB  - Nitric oxide has been investigated widely both during neurodevelopment and in
      neurological diseases. However, whilst it has been established that nitric oxide
      producing enzymes of nitric oxide synthase family are expressed in cerebellar
      Purkinje neurons, the effects of nitric oxide on the viability and morphology of
      these neurons remain unknown. Here, we have demonstrated that the activity of
      neuronal nitric oxide synthase, but not the inducible or endothelial forms of
      this enzyme, is required to support the survival of a proportion of cerebellar
      Purkinje neurons in vitro. We discovered that donation of high concentrations of
      exogenous nitric oxide reduces Purkinje neuron survival in culture and that
      peroxynitrite is also toxic to these cells. Finally, we demonstrated that
      exogenous nitric oxide and peroxynitrite reduce both the magnitude and the
      complexity of the neurite arbour extended by cerebellar Purkinje neurons. Taken
      together, these findings reveal that whilst a low level of endogenous nitric
      oxide, released by the activity of neuronal nitric oxide synthase, is beneficial
      to cerebellar Purkinje neurons in vitro, high levels of exogenous nitric oxide
      and peroxynitrite are detrimental to both the survival of these neurons and to
      their ability to extend processes and form functional neural networks.

PMID- 21728062
TI  - c-Abl in neurodegenerative disease.
AB  - The c-Abl tyrosine kinase participates in a variety of cellular functions,
      including regulation of the actin cytoskeleton, regulation of the cell cycle, and
      the apoptotic/cell cycle arrest response to stress, and the Abl family of kinases
      has been shown to play a crucial role in development of the central nervous
      system. Recent studies have shown c-Abl activation in human Alzheimer's and
      Parkinson's diseases and c-Abl activation in mouse models and neuronal culture in
      response to amyloid beta fibrils and oxidative stress. Overexpression of active c
      Abl in adult mouse neurons results in neurodegeneration and neuroinflammation.
      Based on this evidence, a potential role for c-Abl in the pathogenesis of
      neurodegenerative disease is discussed, and we attempt to place activation of c
      Abl in context with other known contributors to neurodegenerative pathology.

PMID- 21728063
TI  - Role of autophagy in early brain injury after experimental subarachnoid
      hemorrhage.
AB  - Autophagy is a self-degradative process and it plays a housekeeping role in
      removing misfolded or aggregated proteins, clearing damaged organelles, and
      eliminating intracellular pathogens. Previous studies have demonstrated that
      autophagy pathway was activated in brain after experimental subarachnoid
      hemorrhage (SAH); however, the role of autophagy in the pathogenesis of early
      brain injury (EBI) following SAH remains unknown. Experiment 1 aimed to
      investigate the time-course of the autophagy in the cortex following SAH. In
      experiment 2, we chose the maximum time point of autophagy activation and
      assessed the effects of rapamycin (RAP, autophagy activator) and 3-methyladenine
      (3-MA, autophagy inhibitor) on regulation of EBI. All SAH animals were subjected
      to injection of 0.3 ml fresh arterial, nonheparinized blood into prechiasmatic
      cistern in 20 s. As a result, microtubule-associated protein light chain-3 (LC3),
      a biomarker of autophagosome, and beclin-1, a Bcl-2-interacting protein required
      for autophagy, were significantly increased at the early stage of SAH and their
      expressions peaked at 24 h after SAH. In RAP-treated group, the early brain
      damage such as brain edema, blood-brain barrier (BBB) impairment, cortical
      apoptosis, and clinical behavior scale was significantly ameliorated in
      comparison with vehicle-treated SAH rats. Conversely, 3-MA decreased expression
      of LC3 and beclin-1, increased the average value of brain edema and BBB
      disfunction, and aggravated neurological deficits. Our results suggest that
      autophagy pathway is activated in the brain after SAH and may play a beneficial
      role to EBI development.

PMID- 21728064
TI  - Changes in Pirh2 and p27kip1 expression following traumatic brain injury in adult
      rats.
AB  - Pirh2, a p53-induced ubiquitin-protein ligase, has been reported to promote
      ubiquitin-dependent degradation of p27(kip1), which plays an essential role in
      mammalian cell cycle regulation and neurogenesis in the developing central
      nervous system (CNS). However, their distributions and functions in the nervous
      system lesion and repair remain unclear. In this study, we observed that the up
      regulated expression of Pirh2 was concomitant with decreased p27(kip1) level
      after traumatic brain injury by Western blot and immunohistochemistry.
      Immunofluorescence double-labeling revealed that Pirh2 was mainly co-expressed
      with GFAP and CD11b. Meanwhile, we also examined the expression profiles of
      proliferating cell nuclear antigen (PCNA) whose changes were correlated with the
      expression of Pirh2. In addition, Pirh2 colocalized with p27(kip1) and PCNA.
      Immunoprecipitation further showed that they interacted with each other in the
      pathophysiology process. In summary, our data indicated Pirh2 might be a negative
      regulator of p27(kip1) and associated with glial proliferation.

PMID- 21728065
TI  - A new method to include the gravitational forces in a finite element model of the
      scoliotic spine.
AB  - The distribution of stresses in the scoliotic spine is still not well known
      despite its biomechanical importance in the pathomechanisms and treatment of
      scoliosis. Gravitational forces are one of the sources of these stresses.
      Existing finite element models (FEMs), when considering gravity, applied these
      forces on a geometry acquired from radiographs while the patient was already
      subjected to gravity, which resulted in a deformed spine different from the
      actual one. A new method to include gravitational forces on a scoliotic trunk FEM
      and compute the stresses in the spine was consequently developed. The 3D geometry
      of three scoliotic patients was acquired using a multi-view X-ray 3D
      reconstruction technique and surface topography. The FEM of the patients' trunk
      was created using this geometry. A simulation process was developed to apply the
      gravitational forces at the centers of gravity of each vertebra level. First the
      "zero-gravity" geometry was determined by applying adequate upwards forces on the
      initial geometry. The stresses were reset to zero and then the gravity forces
      were applied to compute the geometry of the spine subjected to gravity. An
      optimization process was necessary to find the appropriate zero-gravity and
      gravity geometries. The design variables were the forces applied on the model to
      find the zero-gravity geometry. After optimization the difference between the
      vertebral positions acquired from radiographs and the vertebral positions
      simulated with the model was inferior to 3 mm. The forces and compressive
      stresses in the scoliotic spine were then computed. There was an asymmetrical
      load in the coronal plane, particularly, at the apices of the scoliotic curves.
      Difference of mean compressive stresses between concavity and convexity of the
      scoliotic curves ranged between 0.1 and 0.2 MPa. In conclusion, a realistic way
      of integrating gravity in a scoliotic trunk FEM was developed and stresses due to
      gravity were explicitly computed. This is a valuable improvement for further
      biomechanical modeling studies of scoliosis.

PMID- 21728066
TI  - Voiding dysfunction in the female patient: is the "syndrome" paradigm valid?
AB  - Voiding dysfunction in the female patient significantly affects the patient's
      quality of life. The condition is poorly understood, has varied etiology and
      clinical presentation, and lacks standard definitions with no consensus on
      diagnostic criteria. It consists of a constellation of symptoms involving both
      phases of the micturition cycle. Appropriate diagnosis and treatment of female
      lower urinary tract symptoms (LUTS) is of paramount importance. However, the
      differentiation of female LUTS into various syndromes is currently controversial.
      This article comprehensively reviews the commonly encountered female non
      neurogenic LUTS (overactive bladder, interstitial cystitis, and painful bladder
      syndrome); discusses the contemporary management of these syndromes; and
      emphasizes a syndromic approach to the condition.

PMID- 21728067
TI  - Comments on "well-differentiated thyroid carcinoma with concomitant Hashimoto's
      thyroiditis present with less aggressive clinical stage and low recurrence".

PMID- 21728068
TI  - Integration of a pump and an electrical sensor into a membrane-based PDMS
      microbioreactor for cell culture and drug testing.
AB  - To the extent possible, artificial organs should have characteristics that match
      those of the in vivo system. To this end, microfabrication techniques allow us to
      create microenvironments that can help maintain cell organization and
      functionality in in vitro cultures. We present three new microbioreactors, each
      of which allows cells to be cultured in a perfused microenvironment similar to
      that found in vivo. Our microbioreactors use new technology that permits
      integration onto the chip (35 mm * 20 mm) of an electrical sensor, in addition to
      one or more pumping systems and associated perfusion circuitry. The monitoring of
      Caco-2 cell cultures using electrical impedance spectroscopy (EIS) has allowed us
      to measure the effects of cell growth, cellular barrier formation and the
      presence of chemical compounds and/or toxins. Specifically, we have investigated
      the ability of the electrical sensor to maintain appropriate sensitivity and
      precision. Our results show that the sensor was very sensitive not only to the
      presence or the absence of the cells, but also to changes in cell state. Our
      perfused microbioreactors are highly efficient miniaturized tools that are easy
      to operate. We anticipate that they will offer promising new opportunities in
      many types of cell culture research, including drug screening and tissue
      engineering.

PMID- 21728069
TI  - Strengthening prevention program theories and evaluations: contributions from
      social network analysis.
AB  - A majority of school-based prevention programs target the modification of setting
      level social dynamics, either explicitly (e.g., by changing schools'
      organizational, cultural or instructional systems that influence children's
      relationships), or implicitly (e.g., by altering behavioral norms designed to
      influence children's social affiliations and interactions). Yet, in outcome
      analyses of these programs, the rich and complicated set of peer network dynamics
      is often reduced to an aggregation of individual characteristics or assessed with
      methods that do not account for the interdependencies of network data. In this
      paper, we present concepts and analytic methods from the field of social network
      analysis and illustrate their great value to prevention science--both as a source
      of tools for refining program theories and as methods that enable more
      sophisticated and focused tests of intervention effects. An additional goal is to
      inform discussions of the broader implications of social network analysis for
      public health efforts.

PMID- 21728072
TI  - [Infections of the fingers].

PMID- 21728071
TI  - Pleasure in medical practice.
AB  - It is time to challenge the issue of pleasure associated with the core of medical
      practice. Its importance is made clear through its opposite: unhappiness-
      something which affects doctors in a rather worrying way. The paper aims to
      provide a discussion on pleasure on reliable grounds. Plato's conception of
      techne is a convenient model that offers insights into the unique practice of
      medicine, which embraces in a single purposive action several heterogeneous
      dimensions. In Aristotle's Ethics, pleasure appears to play a central role for
      action's assessment and intensification. Pleasure is also tightly associated with
      the Kantian faculty of reflective judgment, which operates at the heart of
      clinical reasoning. Indeed, practicing medicine means to deal with the particular
      and the manifold, requiring clinical judgment, but also relying on embodied
      habitus. With Bourdieu's notion of habitus, pleasure is the mark of a happy
      practice, which presupposes a deep involvement in one's field. Throughout our
      inquiry, the question of pleasure comes to offer a critical reappraisal of real
      medical practice and leads to consider ethics more as a component of techne than
      as a separate realm of concern.

PMID- 21728070
TI  - The PCa Tumor Microenvironment.
AB  - The tumor microenvironment (TME) is a very complex niche that consists of
      multiple cell types, supportive matrix and soluble factors. Cells in the TME
      consist of both host cells that are present at tumor site at the onset of tumor
      growth and cells that are recruited in either response to tumor- or host-derived
      factors. PCa (PCa) thrives on crosstalk between tumor cells and the TME.
      Crosstalk results in an orchestrated evolution of both the tumor and
      microenvironment as the tumor progresses. The TME reacts to PCa-produced soluble
      factors as well as direct interaction with PCa cells. In return, the TME produces
      soluble factors, structural support and direct contact interactions that
      influence the establishment and progression of PCa. In this review, we focus on
      the host side of the equation to provide a foundation for understanding how
      different aspects of the TME contribute to PCa progression. We discuss immune
      effector cells, specialized niches, such as the vascular and bone marrow, and
      several key protein factors that mediate host effects on PCa. This discussion
      highlights the concept that the TME offers a potentially very fertile target for
      PCa therapy.

PMID- 21728073
TI  - Hypervolemia rather than arterial calcification and extracoronary atherosclerosis
      is the main determinant of pulse pressure in hemodialysis patients.
AB  - INTRODUCTION: Pulse pressure (PP) has been reported as an independent predictor
      of cardiovascular mortality in hemodialysis patients. In this study, we aimed to
      investigate association of PP with echocardiographic and vascular structural
      changes such as atherosclerosis and arterial calcifications in HD patients.
      PATIENTS AND METHODS: In this cross-sectional study, 108 chronic hemodialysis
      patients (49 male, 59 female, mean age: 46 +/- 13 years) were included.
      Biochemical analyses, echocardiographic and high-resolution carotid Doppler
      examinations were done. Aortic wall and coronary artery calcifications were
      measured with electron beam computed tomography. The degree of carotid artery
      stenosis was measured at four different sites (communis, bulbus, interna and
      externa) in both carotid arteries. RESULTS: PP was strongly correlated with
      systolic (r: 0.82) and diastolic (r: 0.33) blood pressure, left ventricular mass
      index (r: 0.58), left ventricle end diastolic diameter (r: 0.38) and weakly
      correlated with aortic wall calcification score (r: 0.26) and carotid plaque
      score (r: 0.27), but not with coronary artery calcification score. Patients with
      carotid plaque had higher PP than patients without plaque (50 +/- 16 mmHg versus
      44 +/- 14 mmHg, P = 0.05). Patients were divided into three groups according to
      aortic wall calcification score. PP was significantly higher in patients with
      higher aortic wall calcification (54 +/- 16 mmHg) than patients with lower aortic
      wall calcification (44 +/- 15 mmHg, P = 0.04). However, on multivariate linear
      regression analysis for predicting PP, the only significant factor retained was
      left ventricle end diastolic diameter. CONCLUSION: PP was weakly associated with
      large vessel calcification and atherosclerosis in hemodialysis patients. The bulk
      of the effect on PP seems to be due to hypervolemia.

PMID- 21728074
TI  - Intraindividual variability of homocysteine and related thiols concentrations in
      follicular fluid.
AB  - PURPOSE: To determine intraindividual variability in concentrations of
      homocysteine and related thiols in follicular fluids of particular follicles
      after ovarian stimulation and assess the differences between follicles with/or
      without oocytes. METHODS: HPLC-FD analysis of plasma and follicular fluid
      cysteine, homocysteine, cysteinylglycine and glutathione in women undergoing IVF.
      RESULTS: In blood plasma, the homocysteine, cysteine, and cysteinylglycine
      concentrations decreased significantly during stimulation with rec FSH (p<0.001).
      We found significant differences in concentrations of cysteine and glutathione
      between follicles with or without retrieved oocytes. High intraindividual
      variability in concentrations of thiols was determined. CONCLUSIONS: The
      concentration variability of thiols between single follicles is very high and we
      recommend mean at least from 3 follicles with/or without oocytes for
      characterization of each woman. It is the best to examine individual follicles
      for further research and analysis of fertility outcomes.

PMID- 21728075
TI  - Analysis of failure following anterior screw fixation of Type II odontoid
      fractures in geriatric patients.
AB  - Anterior screw fixation of Type II odontoid fractures has been recommended. Only
      few publications analyse the mechanism of failure in geriatric patients. We
      reviewed 18 male and 15 female patients aged 65 and above for parameters that
      influence the development of postoperative loss of correction, delayed union or
      non-union. Patients were stratified in two groups: 21 cases in Group A (union)
      and 12 patients in Group B (loss of correction, delayed union, non-union,
      revision surgery). Statistically significant correlation (p < 0.05) could be
      detected between failure to heal and: (1) degenerative changes in the atlanto
      odontoid joint, (2) severity of osteoporosis in the odontoid process, (3)
      posterior oblique fracture type, (4) suboptimal fracture reduction, (5)
      suboptimal position of implant following demanding intraoperative conditions, (6)
      quality of fracture compression and (7) severity of fracture comminution. The
      overall morbidity and mortality rates were 29.0 and 8.6%, respectively. Our
      results indicate that these factors should be addressed regarding the selection
      of the operative treatment method in the geriatric patient.

PMID- 21728076
TI  - Frequency of fragmented QRS on ECG is increased in patients with rheumatoid
      arthritis without cardiovascular disease: a pilot study.
AB  - Myocardial fibrosis causes the fragmentation of QRS complexes (fQRS) on ECGs. We
      hypothesized that the frequency of fQRS could be more common in patients with
      rheumatoid arthritis (RA) than in control subjects. A total of 56 patients with
      RA were compared with 35 age- and gender-matched fibromyalgia subjects for fQRS.
      The fQRS was defined as the presence of an additional R wave, or notching of the
      R or S wave, or the presence of fragmentation in 2 contiguous leads corresponding
      to the territory of a major coronary artery. Patients with bundle block on ECG
      and cardiovascular disease were excluded. Twenty-one patients (37.5%) in the RA
      group had fQRS, while two patients in the control group (5.7%) had fQRS (p =
      0.001). No differences were found between the groups in terms of age, gender, or
      drug use. Duration of disease--years (interquartile range [IQR])--was 10 (8) in
      the fQRS (+) group, while it was 5 (2) in the fQRS (-) group (p < 0.001).
      Multivariate logistic regression analysis revealed that duration of disease was
      associated with the presence of fQRS (B = 1.5, odds ratio = 4.5, p = 0.004, 95%
      confidence interval = 1.6-12.7). We found that fQRS on ECG was more common in
      patients with RA without cardiovascular disease than in age- and gender-matched
      control subjects.

PMID- 21728077
TI  - The contribution of chromosomal abnormalities to congenital heart defects: a
      population-based study.
AB  - We aimed to assess the frequency of chromosomal abnormalities among infants with
      congenital heart defects (CHDs) in an analysis of population-based surveillance
      data. We reviewed data from the Metropolitan Atlanta Congenital Defects Program,
      a population-based birth-defects surveillance system, to assess the frequency of
      chromosomal abnormalities among live-born infants and fetal deaths with CHDs
      delivered from January 1, 1994, to December 31, 2005. Among 4430 infants with
      CHDs, 547 (12.3%) had a chromosomal abnormality. CHDs most likely to be
      associated with a chromosomal abnormality were interrupted aortic arch (type B
      and not otherwise specified; 69.2%), atrioventricular septal defect (67.2%), and
      double-outlet right ventricle (33.3%). The most common chromosomal abnormalities
      observed were trisomy 21 (52.8%), trisomy 18 (12.8%), 22q11.2 deletion (12.2%),
      and trisomy 13 (5.7%). In conclusion, in our study, approximately 1 in 8 infants
      with a CHD had a chromosomal abnormality. Clinicians should have a low threshold
      at which to obtain testing for chromosomal abnormalities in infants with CHDs,
      especially those with certain types of CHDs. Use of new technologies that have
      become recently available (e.g., chromosomal microarray) may increase the
      identified contribution of chromosomal abnormalities even further.

PMID- 21728078
TI  - The relative rates of thiol-thioester exchange and hydrolysis for alkyl and aryl
      thioalkanoates in water.
AB  - This article reports rate constants for thiol-thioester exchange (k (ex)), and
      for acid-mediated (k (a)), base-mediated (k (b)), and pH-independent (k (w))
      hydrolysis of S-methyl thioacetate and S-phenyl 5-dimethylamino-5-oxo
      thiopentanoate-model alkyl and aryl thioalkanoates, respectively-in water.
      Reactions such as thiol-thioester exchange or aminolysis could have generated
      molecular complexity on early Earth, but for thioesters to have played important
      roles in the origin of life, constructive reactions would have needed to compete
      effectively with hydrolysis under prebiotic conditions. Knowledge of the kinetics
      of competition between exchange and hydrolysis is also useful in the optimization
      of systems where exchange is used in applications such as self-assembly or
      reversible binding. For the alkyl thioester S-methyl thioacetate, which has been
      synthesized in simulated prebiotic hydrothermal vents, k (a) = 1.5 * 10(-5) M(-1)
      s(-1), k (b) = 1.6 * 10(-1) M(-1) s(-1), and k (w) = 3.6 * 10(-8) s(-1). At pH 7
      and 23 degrees C, the half-life for hydrolysis is 155 days. The second-order rate
      constant for thiol-thioester exchange between S-methyl thioacetate and 2
      sulfonatoethanethiolate is k (ex) = 1.7 M(-1) s(-1). At pH 7 and 23 degrees C,
      with [R"S(H)] = 1 mM, the half-life of the exchange reaction is 38 h. These
      results confirm that conditions (pH, temperature, pK (a) of the thiol) exist
      where prebiotically relevant thioesters can survive hydrolysis in water for long
      periods of time and rates of thiol-thioester exchange exceed those of hydrolysis
      by several orders of magnitude.

PMID- 21728079
TI  - The activity of Rubisco's molecular chaperone, Rubisco activase, in leaf
      extracts.
AB  - Rubisco frequently undergoes unproductive interactions with its sugar-phosphate
      substrate that stabilize active sites in an inactive conformation. Restoring
      catalytic competence to these sites requires the "molecular chiropractic"
      activity of Rubisco activase (activase). To make the study of activase more
      routine and physiologically relevant, an assay was devised for measuring activase
      activity in leaf extracts based on the ATP-dependent activation of inactive
      Rubisco. Control experiments with an Arabidopsis activase-deficient mutant
      confirmed that the rate of Rubisco activation was dependent on the concentration
      of activase in the extracts. Activase catalyzed Rubisco activation at rates
      equivalent to 9-14% catalytic sites per min in desalted extracts of Arabidopsis,
      camelina, tobacco, cotton, and wheat. Faster rates were observed in a transgenic
      line of Arabidopsis that expresses only the beta-isoform of activase, whereas no
      activity was detected in a line that expresses only the alpha-isoform. Activase
      activity was also low or undetectable in rice, maize, and Chlamydomonas,
      revealing differences in the stability of the enzyme in different species. These
      differences are discussed in terms of the ability of activase subunits to remain
      associated or to reassociate into active oligomers when the stromal milieu is
      diluted by extraction. Finally, the temperature response of activase activity in
      leaf extracts differed for Arabidopsis, camelina, tobacco, and cotton,
      corresponding to the respective temperature responses of photosynthesis for each
      species. These results confirmed the exceptional thermal lability of activase at
      physiological ratios of activase to Rubisco.

PMID- 21728080
TI  - Comparison of postoperative pharyngeal morbidity using the Macintosh laryngoscope
      or AirWay Scope after mastectomy.
AB  - We compared the characteristics of postoperative pharyngeal morbidity in
      intubation between the AirWay Scope (AWS) and Macintosh laryngoscope in 68 ASA I
      II female patients aged 35-77 years in a randomized, double-blinded, controlled
      fashion. After induction of general anesthesia, the patient's trachea was
      intubated using the AWS or Macintosh laryngoscope by five anesthesiologists.
      Before leaving the operating room, postoperative sore throat, hoarseness, and
      dysphagia were assessed, and oral bleeding was evaluated by observation of the
      extubated tracheal tube. On the day after surgery, pharyngeal complications were
      evaluated again, and patients were questioned on delay of oral intake. Incidence
      of sore throat with the AWS (27.2%) was significantly lower than that with the
      Macintosh laryngoscope (52.9%) on the day of surgery. Severity of sore throat
      with the AWS was also significantly less compared with the Macintosh
      laryngoscope. Incidence of oral bleeding with the AWS (6.1%) was significantly
      lower than that with the Macintosh laryngoscope (23.5%). Pharyngeal morbidity on
      the day after surgery did not differ between groups, and no patient complained of
      delayed oral intake. In female patients, the AWS successfully reduced the
      incidence and severity of sore throat on the day of surgery in comparison with
      the Macintosh laryngoscope.

PMID- 21728081
TI  - Preface. Guidelines for diagnosis and treatment of anaerobic infections.

PMID- 21728082
TI  - Preface. Guidelines for diagnosis and treatment of anaerobic infections.

PMID- 21728084
TI  - Chapter 1-1. Anaerobic infections (General): epidemiology of anaerobic
      infections.

PMID- 21728085
TI  - Chapter 1-2. Anaerobic infections (general): testing anaerobic infections.

PMID- 21728086
TI  - Chapter 1-3. Anaerobic infections (general): drug susceptibility tests.

PMID- 21728087
TI  - Chapter 1-4. Anaerobic infections (general): selection of appropriate anti
      anaerobic agents--internal medicine.

PMID- 21728088
TI  - Chapter 1-5. Anaerobic infections (general): selection of appropriate anti
      anaerobic agents--surgery.

PMID- 21728089
TI  - Chapter 1-6. Anaerobic infections (general): care needed when dealing with
      patients who have underlying diseases or complications.

PMID- 21728090
TI  - Chapter 2-1. Anaerobic infections (individual fields): respiratory infections.

PMID- 21728091
TI  - Chapter 2-2. Anaerobic infections (individual fields): blood stream infections
      with anaerobic bacteria.

PMID- 21728092
TI  - Chapter 2-3. Anaerobic infections (individual fields): central nervous system
      infections (brain abscess, subdural abscess, epidural abscess and bacterial
      meningitis).

PMID- 21728093
TI  - Chapter 2-4. Anaerobic infections (individual fields): infections in the
      pediatric field.

PMID- 21728094
TI  - Chapter 2-5-1. Anaerobic infections (individual fields): prevention and treatment
      of postoperative infections.

PMID- 21728095
TI  - Chapter 2-5-2. Anaerobic infections (individual fields): anaerobic infections of
      the head and neck.

PMID- 21728096
TI  - Chapter 2-5-3a. Anaerobic infections (individual fields): skin and soft tissue
      infections.

PMID- 21728097
TI  - Chapter 2-5-3b. Anaerobic infections (individual fields): skin and soft tissue
      infections--bite infections.

PMID- 21728098
TI  - Chapter 2-5-3c. Anaerobic infections (individual fields): skin and soft tissue
      infections--foot infection.

PMID- 21728099
TI  - Chapter 2-5-4. Anaerobic infections (individual fields): intraperitoneal
      infections (acute peritonitis, hepatobiliary infections, etc.).

PMID- 21728100
TI  - Chapter 2-6-1. Anaerobic infections (individual fields): female genital
      infections.

PMID- 21728101
TI  - Chapter 2-6-2. Anaerobic infections (individual fields): bacterial vaginosis.

PMID- 21728102
TI  - Chapter 2-7. Anaerobic infections (individual fields): urogenital infections.

PMID- 21728103
TI  - Chapter 2-8. Anaerobic infections (individual fields): infections in the field of
      orthopedics (primarily bone and joint infections).

PMID- 21728104
TI  - Chapter 2-9. Anaerobic infections (individual fields): ophthalmologic infections.

PMID- 21728105
TI  - Chapter 2-10. Anaerobic infections (individual fields): dental and oral
      infections.

PMID- 21728106
TI  - Chapter 2-11. Anaerobic infections (individual fields): otorhinolaryngological
      infections.

PMID- 21728107
TI  - Chapter 2-12-1. Anaerobic infections (individual fields): actinomycosis.

PMID- 21728108
TI  - Chapter 2-12-2. Anaerobic infections (individual fields): necrotizing
      enterocolitis (neonatal necrotizing enterocolitis).

PMID- 21728109
TI  - Chapter 2-12-3. Anaerobic infections (individual fields): botulism.

PMID- 21728110
TI  - Chapter 2-12-4. Anaerobic infections (individual fields): tetanus.

PMID- 21728112
TI  - Chapter 2-12-6. Anaerobic infections (individual fields): food poisoning due to
      Clostridium perfringens.

PMID- 21728111
TI  - Chapter 2-12-5. Anaerobic infections (individual fields): necrotizing fasciitis.

PMID- 21728113
TI  - Chapter 2-12-7. Anaerobic infections (individual fields): antibiotic-associated
      diarrhea and enterocolitis.

PMID- 21728114
TI  - Chapter 3-1. Appendix: Latest classification and nomenclature for anaerobes.

PMID- 21728115
TI  - Chapter 3-2. Appendix: Anaerobes constituting the indigenous flora.

PMID- 21728116
TI  - Chapter 3-3. Appendix: Drug-resistant anaerobes.

PMID- 21728117
TI  - Chapter 3-4. Appendix: Antimicrobial agents indicated for anaerobes (listed by
      dosing route and chemical class).

PMID- 21728118
TI  - Chapter 3-5. Appendix: Pharmacokinetics of antimicrobial agents indicated for
      anaerobic infections.

PMID- 21728119
TI  - Delay in I(min) channel activation induced by dissociation of Homer proteins in
      A431 cells.

PMID- 21728120
TI  - The combined antidiabetogenic and anticoagulation effecta of tripeptide Gly-Pro
      Arg as estimated in the model of persistent hyperglycemia in rats.

PMID- 21728121
TI  - The role of membrane cholesterol in neurotransmitter release from motor nerve
      terminals.

PMID- 21728122
TI  - Specific isoforms of plasminogen in patients with prostate cancer.

PMID- 21728123
TI  - Epigenetic and pharmacological regulation of the amyloid-degrading enzyme
      neprilysin results in modulation of cognitive functions in mammals.

PMID- 21728124
TI  - The biochemical aspects of the relationship in the parasite-host system as
      exemplified by Kittiwake and cestodes from different systematic groups.

PMID- 21728125
TI  - A new vibrissa group in insectivores (Mammalia, Insectivora) and its role in
      orientation.

PMID- 21728126
TI  - Annual dynamics of the body temperature in musk oxen (Ovibos moschatus) under the
      conditions of Yakutia.

PMID- 21728127
TI  - Ejection of specialized electric discharges during prey pursuit and unspecialized
      electric activity related to respiratory behavior of the clariid catfish Clarias
      macrocephalus (Clariidae, Siluriformes).

PMID- 21728128
TI  - Specific features of ABA-dependent gene expression in spring wheat during cold
      adaptation.

PMID- 21728129
TI  - Development of the bony skeleton in two salamander species (Mertensiella
      caucasica and Chioglossa lusitanica: Salamandridae) with partial embryonization.

PMID- 21728130
TI  - Contrasts in syntax of the advertising songs of closely related warbler species
      (Phylloscopus, Sylviidae).

PMID- 21728131
TI  - Alternative modes of reproduction in populations of Lymnaea stagnalis
      (Gastropoda, Pulmonata) as a factor of temperature adaptation.

PMID- 21728132
TI  - Influence of microphase stratification of soil gels on catalase activity of
      soils.

PMID- 21728133
TI  - Structural differences between the shafts of mammalian vibrissae and hairs and
      their causes.

PMID- 21728135
TI  - Dynamic combinatorial self-replicating systems.
AB  - Thanks to their intrinsic network topologies, dynamic combinatorial libraries
      (DCLs) represent new tools for investigating fundamental aspects related to self
      organization and adaptation processes. Very recently the first examples
      integrating self-replication features within DCLs have pushed even further the
      idea of implementing dynamic combinatorial chemistry (DCC) towards minimal
      systems capable of self-construction and/or evolution. Indeed, feedback loop
      processes - in particular in the form of autocatalytic reactions - are keystones
      to build dynamic supersystems which could possibly approach the roots of
      "Darwinian" evolvability at mesoscale. This topic of current interest also shows
      significant potentialities beyond its fundamental character, because truly smart
      and autonomous materials for the future will have to respond to changes of their
      environment by selecting and by exponentially amplifying their fittest
      constituents.

PMID- 21728134
TI  - ADAR proteins: double-stranded RNA and Z-DNA binding domains.
AB  - Adenosine deaminases acting on RNA (ADAR) catalyze adenosine to inosine editing
      within double-stranded RNA (dsRNA) substrates. Inosine is read as a guanine by
      most cellular processes and therefore these changes create codons for a different
      amino acid, stop codons or even a new splice-site allowing protein diversity
      generated from a single gene. We review here the current structural and molecular
      knowledge on RNA editing by the ADAR family of protein. We focus especially on
      two types of nucleic acid binding domains present in ADARs, namely the dsRNA and
      Z-DNA binding domains.

PMID- 21728136
TI  - Synthesis of pyrrole and carbazole alkaloids.
AB  - An overview of recent transition metal-catalyzed syntheses of pyrroles and
      carbazoles is presented. The focus is on methods which have been applied to the
      preparation of biologically active naturally occurring pyrrole and carbazole
      alkaloids. For pyrroles, special attention is paid to silver(I)-catalyzed
      cyclization reactions. For carbazoles, iron(0)-mediated and palladium(0/II)
      catalyzed cyclization reactions are highlighted and their broad range of
      applications is discussed.

PMID- 21728137
TI  - Bismuth salts in catalytic alkylation reactions.
AB  - Alkylation reactions utilizing nontoxic Lewis acid catalysts and "green"
      alkylating reagents are of high interest due to the continuous need for
      environmentally benign C-C and C-X bond formation. This article shows recent
      advances in Bi(III)-catalyzed alkylations of arenes, 2,4-pentanediones and
      various oxygen- and nitrogen-containing nucleophiles. Instead of toxic alkyl
      halides, the electrophilic components for these transformations were benzyl and
      propargyl alcohols as well as substrates with activated double bonds such as
      styrenes. The fact that Bi(III) salts are capable of activating both sigma- and
      pi-donors highlights their unique character as versatile catalysts for catalytic
      alkylation reactions. In addition, Bi(III) salts are less toxic and cheaper than
      other Lewis acids that have been described for similar transformations.

PMID- 21728138
TI  - The PrP-like proteins Shadoo and Doppel.
AB  - An almost unique place within protein databases, twenty-five years of study has
      underscored the enigmatically subtle role of PrP(C) in normal cell biology. It
      seems that PrP has evolved (and survived) to perform a function that does not
      have a precedent amongst transmembrane cell-surface proteins, perhaps
      representing a new type of plasma membrane ecosystem. In a context where we await
      a clarifying insight to unify a panoply of PrP(C) data into logical molecular
      framework, the GPI-anchored N-glycosylated Doppel and Sho proteins are
      tantalizing in that they correspond roughly to the front and back halves of
      PrP(C) itself. These molecules may be simpler - and more "understandable" -
      entities that can be pursued in parallel to PrP(C), and could open up the biology
      of mammalian prion proteins from fresh directions. Dpl has a profound role in
      successful gametogenesis that warrants close scrutiny and a case for deeper study
      can be made for Sho, a recently discovered CNS-expressed protein with many
      parallels to established facets of PrP biochemistry. In an aerial view of
      biomedical research, Sho and Dpl can be considered as adjacent islands in a prion
      protein archipelago. As such, the coming years of molecular exploration should be
      extremely interesting.

PMID- 21728139
TI  - Epigenetics: genetics versus life experiences.
AB  - Epigenetics is the field of research that examines alterations in gene expression
      caused by mechanisms other than changes in DNA sequence. ADHD is highly
      heritable; however, epigenetics are considered relevant in potentially explaining
      the variance not accounted for by genetic influence. In this chapter, some of the
      well-known processes of epigenetics, such as chromosome organization, DNA
      methylation, and effects of transcriptional factors are reviewed along with
      studies examining the role of these processes in the pathophysiology of ADHD.
      Potential epigenetic factors conferring risk for ADHD at various developmental
      stages, such as alcohol, tobacco, toxins, medications, and psychosocial stressor
      are discussed. Animal studies investigating ADHD medications and changes in CNS
      Gene/Protein Expression are also explored since they provide insight into the
      neuronal pathways involved in ADHD pathophysiology. The current limited data
      suggest that identification of the epigenetic processes involved in ADHD is
      extremely important and may lead to potential interventions that may be applied
      to modify the expression of deleterious, as well as protective, genes.

PMID- 21728140
TI  - Discovery and molecular mapping of a new gene conferring resistance to stem rust,
      Sr53, derived from Aegilops geniculata and characterization of spontaneous
      translocation stocks with reduced alien chromatin.
AB  - This study reports the discovery and molecular mapping of a resistance gene
      effective against stem rust races RKQQC and TTKSK (Ug99) derived from Aegilops
      geniculata (2n = 4x = 28, U(g)U(g)M(g)M(g)). Two populations from the crosses
      TA5599 (T5DL-5M(g)L.5M(g)S)/TA3809 (ph1b mutant in Chinese Spring background) and
      TA5599/Lakin were developed and used for genetic mapping to identify markers
      linked to the resistance gene. Further molecular and cytogenetic characterization
      resulted in the identification of nine spontaneous recombinants with shortened
      Ae. geniculata segments. Three of the wheat-Ae. geniculata recombinants (U6154
      124, U6154-128, and U6200-113) are interstitial translocations (T5DS.5DL-5M(g)L
      5DL), with 20-30% proximal segments of 5M(g)L translocated to 5DL; the other six
      are recombinants (T5DL-5M(g)L.5M(g)S) have shortened segments of 5M(g)L with
      fraction lengths (FL) of 0.32-0.45 compared with FL 0.55 for the 5M(g)L segment
      in the original translocation donor, TA5599. Recombinants U6200-64, U6200-117,
      and U6154-124 carry the stem rust resistance gene Sr53 with the same infection
      type as TA5599, the resistance gene donor. All recombinants were confirmed to be
      genetically compensating on the basis of genomic in situ hybridization and
      molecular marker analysis with chromosome 5D- and 5M(g)-specific SSR/STS-PCR
      markers. These recombinants between wheat and Ae. geniculata will provide another
      source for wheat stem rust resistance breeding and for physical mapping of the
      resistance locus and crossover hot spots between wheat chromosome 5D and
      chromosome 5M(g)L of Ae. geniculata.

PMID- 21728141
TI  - Neurospora crassa homologue of Neuronal Calcium Sensor-1 has a role in growth,
      calcium stress tolerance, and ultraviolet survival.
AB  - NCU04379 gene encodes a conserved Ca(2+) and/or calmodulin binding protein that
      possesses a consensus signal for N-terminal myristoylation and four EF-hands,
      characteristics of Neuronal Calcium Sensor-1proteins. The NCU04379.2 knockout
      mutant shows slow growth rate, increased sensitivity to calcium and ultraviolet
      (UV) irradiation, and a wild-type fragment carrying NCU04379 gene complements the
      mutant. Therefore, NCU04379 gene has a role in growth, calcium stress tolerance,
      and UV survival. Crosses homozygous for DeltaNCU04379.2 mutant strains were fully
      fertile; however, we found evidence for involvement of Ca(2+)/calmodulin
      dependent protein kinase encoding genes NCU02283 and NCU09123 in sexual
      development.

PMID- 21728142
TI  - [Non-purulent meningoencephalitis in children].

PMID- 21728143
TI  - [Challenges in the differential diagnosis of aseptic meningo-encephalitis in
      children].

PMID- 21728144
TI  - [Air conducted ocular VEMP: II. First clinical investigations].
AB  - BACKGROUND: Vestibular-evoked myogenic potentials (VEMP) are widely used to
      assess vestibular function. Air conducted (AC) cervical VEMP (cVEMP) reflect
      sacculus and inferior vestibular nerve function. Ocular VEMP (oVEMP) however has
      been hardly examined up to now. In recent studies it has been assumed that AC
      oVEMP probably reflects superior vestibular nerve function. The aim of this pilot
      study was to evaluate clinical application of the AC oVEMP. MATERIAL AND METHODS:
      AC oVEMP were recorded in patients with peripheral vestibular disorders (n=21).
      In addition thermal irritation and head impulse test were performed and AC cVEMP
      were recorded. For intense AC-sound stimulation tone bursts (500 Hz) with 100 dB
      nHL were used. RESULTS: In peripheral vestibular disorders AC oVEMP and AC cVEMP
      could be classified into: * type 1 (inferior vestibular neuritis) with loss of AC
      oVEMP but normal AC cVEMP, * type 2, probable type of superior vestibular
      neuritis, showing present AC cVEMP but loss of AC oVEMP, * type 3, probable
      complete vestibular neuritis, without AC oVEMP and AC cVEMP. CONCLUSIONS: AC
      oVEMP may be used as an appropriate test for clinical investigation in patients
      with vestibular disorders. AC oVEMP is an additional, essential test for
      assessing otolith function beside AC cVEMP. Further vestibular test are necessary
      for precise clinical interpretation.

PMID- 21728145
TI  - [Intraductal application of Levovist(r) in salivary glands of animals].
AB  - BACKGROUND: Several methods are well established for the imaging of salivary
      glands. Excluding the invasive method sialendoscopy all other methods show the
      salivary duct system inadequately. The aim of this study is to demonstrate a
      method to visualize the salivary duct system by B-mode ultrasound. MATERIAL AND
      METHODS: In 10 parotid glands of common pig cadavers the ultrasound contrast
      agent Levovist ((r)), which is galactose stabilized by palmitic acid was applied
      into the main salivary ducts while simultaneously performing a transcutaneous B
      mode ultrasound. RESULTS: In all cadavers a visualization of the salivary duct
      system could be achieved by the application of Levovist ((r)) because of contrast
      enhancement. This effect arises as a result of an increased reflection of
      ultrasound waves on the surface of the microbubbles contained in the contrast
      agent. CONCLUSION: A reproducible visualization of the salivary duct system with
      B-mode ultrasound is possible by an intraductal application of an ultrasound
      contrast agent. In future this could be established as a reliable and fast method
      for imaging of the salivary ducts without ionizing radiation for the patient.

PMID- 21728146
TI  - [Benefits and importance of tonsillectomy in children and youth with PFAPA
      syndrome].
AB  - BACKGROUND: PFAPA syndrome is characterized by periodic fever, aphthous
      stomatitis, pharyngitis and cervical adenitis. Tonsillectomy and
      adenotonsillectomy are surgical treatment options for this periodic fever
      syndrome, the significance of which will be discussed. MATERIAL AND METHODS:
      Between 2004 and 2010 we collected data of 36 patients with the diagnosis of
      PFAPA syndrome. Data analysis was carried out on the basis of structured
      questionnairs, patients' files as well as a systematic evaluation of
      international literature up to April 2011. RESULTS: The average age for the
      appearance of PFAPA episodes was 22 months and they recurred for an average
      duration of 3-5 days every 14-33 days. During a PFAPA attack, aphthous stomatitis
      was present in 70% of the patients, pharyngitis was present in 93% and cervical
      adenitis in 96%. The family history for recurrent fever was positive in 4 of the
      patients. In 85% cortikosteroids were the only effective medicative treatment
      with no further symptoms until the next attack. Surgery (tonsillectomy+/
      adenoidectomy) aborted the PFAPA episodes in 10 of 16 patients, in 2 patients the
      frequency of episodes decreased, 3 patients had no noticeable change and 1
      patient died as a result of postsurgical bleeding at another institution. After
      an average duration of illness of 4 years the PFAPA syndrome was in spontaneous
      remission in 8 patients. CONCLUSION: Tonsillectomy is an effective treatment
      option for the PFAPA syndrome. Contrary to a general indication the decision
      should be personalized considering the benefit vs. the risk of operation with the
      advice of an ENT specialist.

PMID- 21728147
TI  - Protocatechualdehyde synergizes with aspirin at the platelet cyclooxygenase-1
      level.
AB  - Polyphenol-aspirin interactions were recently identified; however, the
      interaction mode and underlying mechanisms remained elusive. Here, we
      quantitatively assessed the potential interactions among two important
      polyphenolic compounds, caffeic acid (CA) and protocatechualdehyde (Pro), and
      aspirin in the AA-induced platelet aggregation model by applying the isobologram
      and universal response surface approach (URSA) methods. A molecular docking
      approach and an originally developed platelet-associated aspirin clearance
      approach (PAACA) were then applied to explore the potential interaction
      mechanisms. Although Pro and CA themselves exhibited weak inhibitory effect on
      arachidonic acid (AA)-induced platelet aggregation and the production of
      thromboxane B2 (TXB2), both Pro and CA potentiated aspirin action in a
      synergistic manner. The most prominent synergism was found between Pro and
      aspirin. Pro formed a stable complex into the cyclooxygenase-1 (COX-1) channel by
      in silico docking and significantly promoted the platelet-associated aspirin
      clearance, suggesting that the Pro interaction with COX-1 was favorable to the
      binding of aspirin with COX-1. Taken together, our findings suggest that the
      capacity of Pro and potentially other structurally similar polyphenolic compounds
      on promoting the binding of aspirin on platelet COX-1 might be the main mechanism
      of their synergism with aspirin.

PMID- 21728148
TI  - Metabolic characterization of Withania somnifera from different regions of India
      using NMR spectroscopy.
AB  - Withania somnifera (L.) Dun. (Solanaceae), known as Indian ginseng, is one of the
      most popular medicinal plants in India. Considering the importance and common use
      of this plant, it is necessary to investigate its holistic metabolite profile.
      However, with existing analytical methods which are based on TLC and HPLC-UV (or
      MS), it is difficult to obtain information of the whole range of compounds
      appropriately. In this study, the metabolic characterization of Withania
      somnifera leaves, stems, and roots collected in six different regions in India
      was performed using 1H NMR spectroscopy followed by principal component analysis
      (PCA) and hierarchical clustering analysis (HCA). Of the parts of Withania
      somnifera analyzed in this study, the leaf was found to have the widest range of
      metabolites, including amino acids, flavonoids, lipids, organic acids,
      phenylpropanoids, and sugars, as well as the main secondary metabolites of the
      plant, withanolides. The 1H NMR spectra revealed the presence of two groups of
      withanolides: 4-OH and 5,6-epoxy withanolides (withaferin A-like steroids) and 5-
      OH and 6,7-epoxy withanolides (withanolides Alike steroids). The ratio of these
      two withanolides was found to be a key discriminating feature of Withania
      somnifera leaf samples from different origins.

PMID- 21728149
TI  - Isolation and biological activities of phenanthroindolizidine and septicine
      alkaloids from the Formosan Tylophora ovata.
AB  - An investigation of alkaloids present in the leaves and stems of Tylophora ovata
      led to the isolation of two new septicine alkaloids and one new
      phenanthroindolizidine alkaloid, tylophovatines A, B, C (1, 2, and 5),
      respectively, together with two known septicine and six known
      phenanthroindolizidine alkaloids. The structures of the new alkaloids 1, 2, and 5
      were established by means of spectroscopic analyses. These eleven alkaloids show
      in vitro anti-inflammatory activities with IC50 values ranging from 84 nM to 20.6
      MUM through their suppression of nitric oxide production in RAW264.7 cells
      stimulated by lipopolysaccharide and interferon-gamma. Moreover, these substances
      display growth inhibition in HONE-1, NUGC-3, HepG2, SF-268, MCF-7, and NCI-H460
      cancer cell lines, with GI50 values ranging from 4 nM to 24.2 MUM. In addition,
      tylophovatine C (5) and 13a(S)-(+)-tylophorine (7) were found to exhibit potent
      in vivo anti-inflammation activities in a rat paw edema model. Finally, structure
      activity relationships were probed by using the isolated phenanthroindolizidines
      and septicines. Phenanthroindolizidines are suggested to be divided into
      cytotoxic agents (e.g., 10 and 11) and anti-inflammation based anticancer agents
      (e.g., 5-9).

PMID- 21728150
TI  - Antimicrobial, cytotoxic lignans and terpenoids from the twigs of Pseudolarix
      kaempferi.
AB  - Seven new compounds, including four lignans, (+)-(8S,8'S)-9,9'
      dibenzoylsecoisolariciresinol (1), (+)-(8S*,8'R*)-4,4'-dimethyloxomatairesinol
      (2), (+)-(7S*,8R*,8'R*,9'S*)-9'-n-butoxytsugacetal (3), and pseudolarkaemin A
      (4), a pyronane glycoside, pseudolarkaemin B (5), an ent-beyerene glycoside,
      pseudolarkaemin C (6), and a triterpene, 25-epi-pseudolarolide Q (7), along with
      25 known compounds (8-32) were isolated from the twigs of Pseudolarix kaempferi.
      Their structures were elucidated mainly by the analysis of their NMR and MS data.
      Pseudolarolide C acid (24) was isolated for the first time as a natural product.
      All compounds were evaluated for antimicrobial activity against Candida albicans
      and Staphylococcus aureus, and cytotoxic activity against K562, HT-29, B16, BGC
      823, BEL-7402, SGC-7901, U251, and A549 cancer cell lines were assayed. Results
      indicated that the new compounds 3, 7, and some known compounds showed
      antimicrobial and cytotoxic activities.

PMID- 21728151
TI  - Kaempferol regulates the lipid-profile in high-fat diet-fed rats through an
      increase in hepatic PPARalpha levels.
AB  - The aim of this study was to investigate the antiobesity and antihyperlipidemic
      effects of the flavonoid kaempferol (3,5,7,4'-tetrahydroxyflavone). After being
      fed a high-fat diet (HFD) for two weeks, rats were dosed orally with kaempferol
      (75, 150, or 300 mg/kg) or fenofibrate (100 mg/kg) once daily for eight weeks.
      Fenofibrate is an antilipemic agent that exerts its therapeutic effects through
      activation of peroxisome proliferator-activated receptor alpha (PPAR alpha).
      Kaempferol (300 mg/kg/day) produced effects similar to fenofibrate in reducing
      body weight gain, visceral fat-pad weights, plasma lipid levels, as well as the
      coronary artery risk and atherogenic indices of HFD-fed rats. Kaempferol also
      caused dose-related reductions in hepatic triglyceride and cholesterol content
      and lowered hepatic lipid droplet accumulation and the size of epididymal
      adipocytes in HFD-fed rats. Kaempferol and fenofibrate reversed the HFD-induced
      downregulation of hepatic PPAR alpha. HFD-induced reductions in the hepatic
      levels of acyl-CoA oxidase (ACO), and cytochrome P450 isoform 4A1 (CYP4A1)
      proteins were reversed by kaempferol and fenofibrate. The elevated expression of
      hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats were
      lowered by kaempferol and fenofibrate. These results suggest that kaempferol
      reduced the accumulation of visceral fat and improved hyperlipidemia in HFD-fed
      obese rats by increasing lipid metabolism through the downregulation of SREBPs
      and promoting the hepatic expression of ACO and CYP4A1, secondary to a direct
      upregulation hepatic PPAR alpha expression.

PMID- 21728152
TI  - [The global importance of tuberculosis].
AB  - In the western industrialized world tuberculosis has receded from its peak with
      an annual mortality of 1 % some 150 to 250 years ago to currently 10 to 20 new
      cases annually per 100,000 population. The introduction of chemotherapy in the
      1950s reduced case fatality from some 70 % to a small fraction. Nowadays, the
      indigenous elderly and immigrants from high-prevalence countries contribute most
      of tuberculosis morbidity in the industrialized world. In contrast, tuberculosis
      remains a major public health problem in most resource-constrained countries and
      has substantially increased in sub-Saharan Africa as a result of the impact of
      HIV infection. The World Health Organization estimates that each year over 9
      million new cases emerge in the world. Because of weak infrastructures low-income
      countries continue to experience shortages in the drug supply, facilitating the
      emergence of strains resistant to first-line drugs which are difficult or
      impossible to treat. The primordial task for the international community is to
      assist in strengthening the necessary infrastructures and to help ensuring that
      patients have unrestricted and uninterrupted access to antituberculosis
      medications and antiretroviral drugs.

PMID- 21728153
TI  - [Tuberculosis in Switzerland].
AB  - Tuberculosis (TB) is currently a rare disease in Switzerland (2.8 per 100'000
      native Swiss), but is still more prevalent in some population groups especially
      among migrants. After more than a century on the decrease, from 2007 to 2009 the
      TB cases have increased from 478 to 556 for unknown reasons. The occurrence of
      multidrug-resistant forms (1.4 % MDR- TB) and the frequently late diagnosis
      represent challenges for the medical profession and the public health
      authorities. The Swiss Lung Associations are engaged with contact examinations
      and therapy of TB cases and support a "TB Manual" with guidelines and a TB
      Hotline.

PMID- 21728154
TI  - [Diagnosing pulmonary tuberculosis].
AB  - Unexplained cough for more than 2 - 3 weeks or patients considered to be at high
      risk for tuberculosis (TB) should be investigated in a timely manner: Chest
      radiography and 3 sputum examinations for detection acid-fast bacilli and TB
      cultures are essential first diagnostic steps. Pending sputum results an
      antibiotic trial (avoiding fluorochinolones) is warranted and if symptoms do not
      resolve and the diagnosis remains unclear then additional investigations are
      required to confirm or rule out pulmonary tuberculosis: sputum provocation by
      inhalation of hypertonic saline or alternatively bronchoscopy may provide samples
      to confirm TB or lead to an alternative diagnosis. Immunologic and molecular
      tests are useful in specific situations to identify previous contact with
      specific mycobacteria or identify drug-resistant strains. Prompt diagnosis and
      treatment are important epidemiologic measures to prevent transmission of
      mycobacteria to contacts including the medical personnel. Isolation measures take
      into account the transmission by aerosol and the viability of the mycobacteria
      and specific criteria need to be met before these precautions can be abandoned.

PMID- 21728155
TI  - [Microbiological diagnosis of tuberculosis].
AB  - Tuberculosis continuous to be the world's most important infectious disease in
      addition to malaria and AIDS. One-third of world's population is infected with
      Mycobacterium tuberculosis. Every tenth of those people will develop active
      tuberculosis in his or her lifetime. The global tuberculosis incidence rate is
      falling; however, the rate of decline is less than 1 %. While microscopy and
      culture are still the gold standard in laboratory diagnostic, remarkable
      technical progress has recently been made, upgrading the speed and quality of
      mycobacteriology diagnostic services. The development of improved nucleic acid
      amplification tests enables the detection of M. tuberculosis-DNA as well as the
      determination of drug resistance pattern direct from the specimen. Another
      advance is the implementation of ex vivo interferon-gamma release assays for the
      detection of latent tuberculosis. This paper includes a brief summary of current
      state-of-the-art diagnostic tools which are applied for laboratory diagnosis of
      tuberculosis and drug susceptibility testing.

PMID- 21728156
TI  - [Tuberculosis control].
AB  - Tuberculosis control activities focus on identification and treatment of sputum
      smear positive tuberculosis patients. As soon as these patients can be treated,
      they not only have an optimal chance for cure, they also no longer spread
      Mycobacterium tuberculosis (M.tb) in the community. Screening is a systematic
      search for tuberculosis disease, often performed by radiological or by sputum
      smear examinations. On the other hand, Screening for Infection with M.tb is with
      immunological tests. Persons infected with M.tb have an increased risk to develop
      active tuberculosis in the future. Screening for infection is recommended in
      tuberculosis contact tracing and in several risk groups for the progression to
      tuberculosis disease, specifically before the start of immunosuppressive therapy
      with tumor necrosis factor antagonists or in transplant recipients. Several
      immunological tests are available. If compared to the traditional in vivo Mantoux
      tuberculin skin test, in vitro blood tests called Interferon Gamma Release Assays
      (IGRA) are more specific because the cell wall antigens used for the tests are
      not present in the wall of Bacille Calmitte Guerin BCG and most atypical
      mycobacteria. Another advantage of IGRA is the mitogen positive control, which
      detects unreliable tests in immunodeficiency. Persons found to be infected with
      M.tb are treated with prophylactic isoniacid for 9 months.

PMID- 21728157
TI  - [Tuberculosis and HIV - features of the co-infection].
AB  - The human immunodeficiency virus (HIV) epidemic has allowed the incidence of
      tuberculosis to rise globally and particularly in sub-Saharan Africa. Diagnosis
      and treatment of tuberculosis is more complex in patients with HIV/AIDS. Sputum
      smear microscopy is performing poorly in HIV-infected individuals, who are often
      started on antituberculosis treatment on clinical grounds. The treatment of
      coinfected patients requires antituberculosis and antiretroviral drugs to be
      administered concomittantly; challenges include pill burden and patient
      compliance, drug interactions, overlapping toxic effects, and immune
      reconstitution inflammatory syndrome. Current guidelines recommend starting
      antiretroviral treatment within a few weeks of antituberculosis therapy for
      patients with CD4 cell counts < 350 cells/ul.

PMID- 21728158
TI  - [Medical treatment of tuberculosis - update 2011].
AB  - Tuberculosis is the second most common cause of death from an infectious disease
      after HIV/AIDS and the leading cause of death from an infectious disease in HIV
      co-infected patients. Currently, drug susceptible TB is treated with a four drug
      regimen given over a period of two months followed by two drugs for four months.
      Drug resistant tuberculosis requires more complex and longer treatment with
      alternative substances. New antituberculosis drugs are currently being developed
      and investigated and are urgently needed to treat drug susceptible and drug
      resistant TB.

PMID- 21728159
TI  - [Nontuberculous mycobacterial infections of the lung].
AB  - Nontuberculous mycobacterium (NTM) species are mycobacterial species other than
      those belonging to the Mycobacterium tuberculosis complex and M. leprae. NTM are
      generally free-living organisms that are ubiquitous in the environment. Pulmonary
      disease, especially in older persons with and without underlying lung disease, is
      caused primarily by M. avium complex (MAC) and M. kansasii. The symptoms and
      signs of MAC lung disease are variable and not specific, but include cough,
      malaise, weakness, dyspnoea, chest discomfort and occasionally hemoptoe. Two
      major clinical presentations include disease in those with underlying lung
      disease, primarily white, middle-aged or elderly men - often alcoholics and/or
      smokers with underlying chronic obstructive lung disease, patients in whom MAC
      develops in areas of prior bronchiectasis, and patients with cystic fibrosis; and
      those without known underlying lung disease, including non-smoking women over age
      50 who have interstitial patterns on chest radiography. M. kansasii infections
      are endemic in cities with infected tap water. Symptoms of the M. kansasii lung
      disease resemble to tuberculosis. M. abszessus is the most pathogenic rapid
      growing Mycobacterium which causes pulmonary infection. The American Thoracic
      Society and Infectious Disease Society of America's diagnostic criteria for
      nontuberculous mycobacterial pulmonary infections include both imaging studies
      consistent with pulmonary disease and recurrent isolation of mycobacteria from
      sputum or isolated from at least one bronchial wash in a symptomatic patient. For
      treatment of MAC lung disease we recommend depending on severity and
      susceptibility testing a three to four drug treatment with a macrolide,
      rifampicin and ethambutol and for M. kansasii a treatment with Isoniazid,
      rifampicin and ethambutol. Surgical management only plays a role in rare and
      special cases. Treatment should be continued until sputum cultures are
      consecutively negative for at least one year.

PMID- 21728160
TI  - [Impact of surgical intervention in the treatment of pulmonary tuberculosis].
AB  - The different modalities in the treatment of tuberculosis (TB) changed within the
      last century. With the beginning of the era of effective antibiotic treatment,
      indication for surgical methods became rare. The combination of different classes
      of antibiotics to treat TB is most often effective but several multi-drug
      resistant germs were created, leading to the need of surgical resection as
      adjuvant treatment. The aim of this review is to summarize the current role of
      surgical therapy in treating TB.

PMID- 21728161
TI  - Computed tomography of the abdomen in Saanen goats: I. reticulum, rumen and
      omasum.
AB  - Computed tomography (CT) of the reticulum, rumen and omasum was carried out in 30
      healthy goats and the images were compared to corresponding body sections
      obtained at postmortem. A multidetector CT was used to examine goats in sternal
      recumbency. A setting of 120 KV and 270 mA was used to produce 1.5-mm transverse
      slices from the fifth thoracic vertebra to the sacrum. Soft tissue structures
      were assessed in a soft tissue with a window width (W) of 400 Hounsfield Units
      (HU), and a window level (L) of 40 HU. The layering of the ruminal contents was
      assessed in an ingesta window with a W of 1500 HU and an L of 30 HU. After
      subjective evaluation, the size of the rumen and omasum, the thickness of the
      walls of the reticulum, rumen and omasum and the height of the gas cap and fibre
      and liquid phases of the rumen were measured. Fifteen goats were euthanised after
      CT examination, placed in sternal recumbency and frozen at -18 oC for three to 10
      days. Thirteen goats were then cut into 1.0- to 1.5-cm-thick transverse slices.
      One goat was cut in dorsal-plane slices and another in sagittal slices. The
      structures in the CT images were identified by using the corresponding anatomical
      slices.

PMID- 21728162
TI  - Computed tomography of the abdomen in Saanen goats: II. liver, spleen, abomasum,
      and intestine.
AB  - This study describes the results of computed tomography (CT) of the liver,
      spleen, abomasum, small intestine and large intestine in 30 healthy Saanen goats.
      CT examination and anatomical slice preparation postmortem were performed as
      described in the first communication. After subjective evaluation of the CT
      images, various variables including the length/size, volume and density of the
      liver, spleen and gallbladder, the wall thickness of the abomasum, small
      intestine and large intestine and the diameter of the intestine were measured.
      The liver, spleen, abomasum, small intestine and large intestine could be
      accurately visualised using CT.

PMID- 21728163
TI  - Computed tomography of the abdomen in Saanen goats: III. kidneys, ureters and
      urinary bladder.
AB  - This study describes the findings of computed tomography (CT) of the kidneys,
      ureters, urinary bladder and adrenal glands in 28 healthy female Saanen goats. CT
      examination and anatomical slice preparation postmortem was performed as
      described in the first communication. After subjective evaluation of the CT
      images, various variables including the size, volume and density of the kidneys,
      the diameter of the ureters and the size of the adrenal glands were measured. The
      targeted organs could be accurately visualised using CT and there was very good
      topographical agreement between the CT images and the anatomical preparations.
      The kidneys, renal vessels, ureters, urinary bladder and adrenal glands were seen
      in all goats.

PMID- 21728164
TI  - [Transportation of veal calves in Switzerland].
AB  - The analysis and optimization of transportation routes of calves to
      slaughterhouses by means of a GIS (geographical information system) route
      planning and time limitation software for the fleet management in transportation
      industry was performed. As basic data the farms (last locations of the calves)
      and the slaughterhouses were available in each case with addresses and
      coordinates. 150 data records from 258 veal calves could be evaluated. None of
      the calves was transported longer than 6 hours. Therefore, in all cases the Swiss
      law for animal protection was obeyed concerning maximum length of transportation
      time. In the road model, 82% of calves were transported too far.

PMID- 21728165
TI  - [In commemoration of Herman Keller 1936-2011].

PMID- 21728167
TI  - [Employment termination without notice - part 2].

PMID- 21728168
TI  - [Regional purchasing power differences].

PMID- 21728169
TI  - Differential requirement of IKK2 for CYLD-dependent representation of thymic and
      peripheral T-cell populations.
AB  - The cylindromatosis tumor suppressor gene (Cyld) encodes an enzyme (CYLD) with
      deubiquitinating activity that has been implicated in the regulation of thymocyte
      selection in an NF-kappaB-essential-modulator (NEMO)-dependent manner. The main
      known molecular defects in thymocytes with inactive CYLD (LckCre-Cyld(flx9/flx9)
      ) are the aberrant hyperactivation of NF-kappaB and JNK pathways. In order to
      dissect further the molecular mechanism of CYLD-dependent thymocyte selection and
      address the role of NF-kappaB specifically, we generated double mutant mice
      (LckCre-Cyld(flx9/flx9) -Ikk2(flx/flx) ) in which CYLD was inactivated
      concomitantly with IKK2 (IkappaB-kinase 2) in thymocytes. Interestingly, thymic
      development and NF-kappaB activity in double mutant mice were fully restored,
      indicating that an IKK2-dependent function of CYLD that leads to the
      hyperactivation of the NF-kappaB pathway is primarily responsible for the
      defective selection of thymocytes. Intriguingly, we observed a greater reduction
      of CD4(+)  and CD8(+)  T cells in the periphery of LckCre-Cyld(flx9/flx9) 
      Ikk2(flx/flx)  mice compared with LckCre-Ikk2(flx/flx)  mice. Collectively, our
      data establish CYLD as a critical regulator of thymocyte selection in a manner
      that depends on IKK2 and NF-kappaB activation. In addition, our data uncover an
      IKK2-independent role for CYLD in the establishment of physiological T-cell
      populations in the periphery.

PMID- 21728170
TI  - Polyclonal Treg cells modulate T effector cell trafficking.
AB  - In this study, we have analyzed the in vivo dynamics of the interaction between
      polyclonal Foxp3(+)  Treg cells, effector T (Teff) cells, and DCs in order to
      further our understanding of the mechanisms of Treg cell-mediated suppression.
      Cotransfer of polyclonal activated Treg cells into healthy mice attenuated the
      induction of EAE. Suppression of disease strongly correlated with a reduced
      number of Teff cells in the spinal cord, but not with Treg cell-mediated
      inhibition of Th1/Th17 differentiation. Cotransfer of Treg cells with TCR-Tg Teff
      cells followed by immunization by multiple routes resulted in an enhanced number
      of Teff cells in the lymph nodes draining the site of immunization without an
      inhibition of Teff-cell differentiation. Fewer Teff cells could be detected in
      the blood in the presence of Treg cells and fewer T cells could access a site of
      antigen exposure in a modified delayed-type hypersensitivity assay. Teff cells
      recovered from LNs in the presence of Treg cells expressed decreased levels of
      CXCR4, syndecan, and the sphingosine phosphate receptor, S1P1 (sphingosine 1
      phosphate receptor 1). Thus, polyclonal Treg cells influence Teff-cell responses
      by targeting trafficking pathways, thus allowing immunity to develop in lymphoid
      organs, but limiting the number of potentially auto-aggressive cells that are
      allowed to enter the tissues.

PMID- 21728171
TI  - Immunogenic cell death of human ovarian cancer cells induced by cytosolic
      poly(I:C) leads to myeloid cell maturation and activates NK cells.
AB  - Owing to high rates of tumor relapse, ovarian cancer remains a fatal disease for
      which new therapeutic approaches are urgently needed. Accumulating evidence
      indicates that immune stimulation may delay or even prevent disease recurrence in
      ovarian cancer. In order to elicit proinflammatory signals that induce or amplify
      antitumor immune reactivity, we mimicked viral infection in ascites-derived
      ovarian cancer cells. By transfection or electroporation we targeted the
      synthetic double-stranded RNA poly(I:C) intracellularly in order to activate
      melanoma differentiation-associated gene-5 (MDA-5), a sensor of viral RNA in the
      cytosol of somatic cells. Cancer cells reacted with enhanced expression of HLA
      class I, release of CXCL10, IL-6, and type I IFN as well as tumor cell apoptosis.
      Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells,
      and subsequently upregulated HLA-class I/II and costimulatory molecules, and
      secreted CXCL10 and IFN-alpha. Further, this proinflammatory milieu promoted
      cytolytic activity and IFN-gamma secretion of NK cells. Thus, our data suggest
      that the engagement of MDA-5 in a whole tumor cell vaccine is a promising
      approach for the immunotherapy of ovarian cancer.

PMID- 21728172
TI  - Double- and monofunctional CD4+ and CD8+ T-cell responses to Mycobacterium
      tuberculosis DosR antigens and peptides in long-term latently infected
      individuals.
AB  - More than 2 billion individuals are latently infected with Mycobacterium
      tuberculosis (Mtb). Knowledge of the key Mtb antigens and responding T-cell
      subsets mediating protection against Mtb is critical for developing improved
      tuberculosis (TB) vaccines. We previously reported that Mtb DosR-regulon-encoded
      antigens are recognized well by human T cells in association with control of Mtb
      infection. The characteristics of the responding T-cell subsets, however,
      remained unidentified. We have therefore studied the cytokine production and
      memory phenotypes of Mtb DosR-regulon-encoded antigen-specific T cells from
      individuals who had been infected with Mtb decades ago, yet never developed TB
      (long-term latent Mtb-infected individuals). Using multi-parameter flow cytometry
      and intracellular cytokine staining for IFN-gamma, TNF-alpha and IL-2, we found
      double and single cytokine-producing CD4(+)  as well as CD8(+)  T cells to be the
      most prominent subsets, particularly IFN-gamma(+)  TNF-alpha(+)  CD8(+)  T cells.
      The majority of these T cells comprised effector memory and effector T cells.
      Furthermore, CFSE labeling revealed strong CD4(+)  and CD8(+)  T-cell
      proliferative responses induced by several "immunodominant" Mtb DosR antigens and
      their specific peptide epitopes. These findings demonstrate the prominent
      presence of double- and monofunctional CD4(+)  and CD8(+)  T-cell responses in
      naturally protected individuals and support the possibility of designing Mtb DosR
      antigen-based TB vaccines.

PMID- 21728173
TI  - CLEC-2 signaling via Syk in myeloid cells can regulate inflammatory responses.
AB  - Myeloid cells express a plethora of C-type lectin receptors (CLRs) that can
      regulate immune responses. CLEC-2 belongs to the Dectin-1 sub-family of CLRs that
      possess an extracellular C-type lectin-like domain and a single intracellular
      hemITAM motif. CLEC-2 is highly expressed on mouse and human platelets where it
      signals via Syk to promote aggregation. We generated a monoclonal antibody (mAb)
      against mouse CLEC-2 and found that CLEC-2 is additionally widely expressed on
      leukocytes and that its expression is upregulated during inflammation. MAb
      mediated crosslinking of CLEC-2 leads to hemITAM-dependent signaling via Syk,
      Ca(2+)  and NFAT and, in myeloid cells, modulates the effect of toll-like
      receptor (TLR) agonists to selectively potentiate production of IL-10. A
      macrophage/dendritic cell-dependent increase in IL-10 is also observed in mice
      given anti-CLEC-2 mAb together with LPS. Collectively, these data indicate that
      CLEC-2 is expressed in myeloid cells and acts as a Syk-coupled CLR able to
      modulate TLR signaling and inflammatory responses.

PMID- 21728174
TI  - TGF-beta signaling via Smad4 drives IL-10 production in effector Th1 cells and
      reduces T-cell trafficking in EAE.
AB  - Effector Th1 cells perpetuate inflammatory damage in a number of autoimmune
      diseases, including MS and its animal model EAE. Recently, a self-regulatory
      mechanism was described in which effector Th1 cells produce the immunomodulatory
      cytokine IL-10 to dampen the inflammatory response in both normal and autoimmune
      inflammation. While the presence of TGF-beta has been suggested to enhance and
      stabilize an IFN-gamma(+) IL-10(+)  phenotype, the molecular mechanism is poorly
      understood. Additionally, in the context of adoptive transfer EAE, it is unclear
      whether IL-10 acts on the transferred Th1 cells or on endogenous host cells. In
      the present study, using myelin-specific TCR-Tg mice, we show that repetitive Ag
      stimulation of effector Th1 cells in the presence of TGF-beta increases the
      population of IFN-gamma(+) IL-10(+)  cells, which correlates with a decrease in
      EAE severity. Additionally, TGF-beta signaling causes binding of Smad4 to the IL
      10 promoter, providing molecular evidence for TGF-beta-mediated IL-10 production
      from Th1 effector cells. Finally, this study demonstrates that IL-10 not only
      reduces encephalitogenic markers such as IFN-gamma and T-bet on Th1 effector
      cells expressing the IL-10R but also prevents recruitment of both transferred and
      host-derived inflammatory T cells. These data establish a regulatory mechanism by
      which highly activated Th1 effector cells modulate their pathogenicity through
      the induction of IL-10.

PMID- 21728175
TI  - Delayed type hypersensitivity-induced myeloid-derived suppressor cells regulate
      autoreactive T cells.
AB  - Mild but efficient treatments of autoimmune diseases are urgently required. One
      such therapy, long-term maintenance of chronic delayed type hypersensitivity, has
      been described for alopecia areata (AA), a hair follicle-affecting autoimmune
      disease. The molecular mechanisms underlying the therapeutic efficacy are
      unknown, but may involve myeloid-derived suppressor cells (MDSCs). AA-affected
      mice were treated with squaric acid dibutyl ester (SADBE). The immunoreactivity
      of SADBE-treated AA lymphocytes and of AA lymphocytes co-cultured with SADBE
      induced MDSCs was analyzed. The curative effect of SADBE was abolished by all
      transretinoic acid, which drives MDSCs into differentiation, confirming a central
      role for MDSCs in therapeutic SADBE treatment. SADBE and SADBE-induced MDSCs
      strongly interfered with sustained autoreactive T-cell proliferation in response
      to AA skin lysate (autoantigen), which was accompanied by weak zeta-chain down
      regulation and strongly impaired Lck activation. In contrast, activation of the
      mitochondrial apoptosis pathway and blockade of the anti-apoptotic PI3K/Akt
      pathway by SADBE-induced MDSCs did not require T-cell receptor engagement.
      Apoptosis induction correlated with high TNF-alpha expression in SADBE-induced
      MDSCs and elevated TNFRI levels in AA lymphocytes. SADBE-induced MDSCs interfere
      with persisting autoreactive T-cell proliferation and promote apoptosis of these
      T cells, which qualifies MDSCs induced and maintained by chronic delayed type
      hypersensitivity reactions as promising therapeutics in organ-related autoimmune
      diseases.

PMID- 21728176
TI  - Fine tuning of IRF-4 expression by SWAP-70 controls the initiation of plasma cell
      development.
AB  - The generation of plasma cells (PCs) is key for proper humoral immune responses.
      The transcription factors IRF-4 and BLIMP-1 (B-lymphocyte induce maturation
      protein-1) control PC commitment, but the underlying regulatory mechanisms are
      incompletely understood. Here we have identified SWAP-70 as being critically
      involved in Toll-like receptor (TLR)-triggered PC differentiation. Upon
      activation through various TLRs, Swap-70(-/-)  B cells were activated and
      proliferated normally. However, expression of BLIMP-1 was markedly reduced and PC
      differentiation was impaired. Four hours of LPS stimulation were sufficient to
      drive PC differentiation, and SWAP-70 was required during this initial period.
      Swap-70(-/-)  B cells pre-activated in vitro failed to efficiently differentiate
      into PCs upon adoptive transfer into recipient mice. Re-introduction of SWAP-70
      into Swap-70(-/-)  B cells rescued their development into PCs, and SWAP-70 over
      expression in wild-type (WT) B cells increased PC generation. In the absence of
      SWAP-70, IRF-4 protein levels were reduced and the IRF-4(high)  B220(+)  CD138(-)
      compartment, including PC precursors, was strongly diminished. Ectopic
      expression of SWAP-70 increases IRF-4 protein levels and PC differentiation in WT
      and Swap-70(-/-)  B cells, and IRF-4 over-expression in Swap-70(-/-)  B cells
      elevates PC differentiation to WT levels. Thus, in a dose-dependent manner, SWAP
      70 controls IRF-4 protein expression and thereby regulates the initiation of PC
      differentiation.

PMID- 21728178
TI  - CE methods for analysis of isoforms of prostate-specific antigen compatible with
      online derivatization for LIF detection.
AB  - Prostate-specific antigen (PSA) is the usual biomarker for prostate cancer (PCa).
      However, its lack of selectivity has lead to the search for new biomarkers. PSA
      glycosylation seems to depend on the pathophysiological conditions of the
      individual. Thus, methods to separate PSA isoforms (peaks) to study their role as
      PCa markers are needed. In this work, CE methods for PSA isoforms separation,
      based on the use of different dynamic coatings, are developed using UV detection.
      Three complementary CE methods allowing the separation of 8 or 9 PSA isoforms are
      selected. The longest method takes only 17 min, while the shortest one separates
      9 isoforms in < 8 min. Depending on the isoforms of interest for their use as PCa
      biomarker, the CE method to be used can be chosen or various of them can be
      combined. A remarkable aspect of these methods is that the BGEs employed are
      devoid of compounds with primary amino groups, making the CE methods compatible
      with fluorescent on-column derivatization through amino residues. As a proof-of
      concept, a preliminary result shows that LIF detection of labeled PSA analyzed by
      one of the three developed methods permits detection of glycoprotein isoforms.

PMID- 21728179
TI  - Protein expression patterns associated with advanced stage ovarian cancer.
AB  - This is a comparative proteomic study on biopsies from patients with ovarian
      cancer to identify potential diagnostic/prognostic biomarkers in both healthy and
      tumor tissue, interstitial fluid (normal interstitial fluid and tumoral
      interstitial fluid and peritoneal effusion. Protein expression/identification was
      evaluated by 2-DE and MS analysis: six proteins showed differential expression in
      tumoral interstitial fluid and tumor tissue compared to normal interstitial fluid
      and healthy tissue: five were found to be downregulated and identified as
      galectin 3, glutathione S-transferase A-2, retinol binding protein 1,
      phosphatidylethanolamine-binding protein and annexin 5, while the calgranulin,
      was significantly upregulated in all pathological samples, including the ascitic
      fluid. Validation of S100A8 overexpression in carcinoma tissue was obtained by
      immunohistochemistry. To our knowledge, this is the first study to report an over
      expression of calgranulin by 2-DE associated with MS/MS analysis on surgical
      biopsy. The reduced expression of galectin 3 and retinol binding protein 1 in
      cystic fluid and serum of patients with early stage disease is confirmed in this
      study. The results highlight alterations in proteins that control cell-cycle
      progression and apoptosis, as well as factors that modulate the activity of
      signal transduction pathways. Moreover, this study suggests that calgranulin
      expression may be used as a diagnostic and/or prognostic biomarker.

PMID- 21728180
TI  - MyMolDB: a micromolecular database solution with open source and free components.
AB  - BACKGROUND: To manage chemical structures in small laboratories is one of the
      important daily tasks. Few solutions are available on the internet, and most of
      them are closed source applications. The open-source applications typically have
      limited capability and basic cheminformatics functionalities. In this article, we
      describe an open-source solution to manage chemicals in research groups based on
      open source and free components. It has a user-friendly interface with the
      functions of chemical handling and intensive searching. RESULTS: MyMolDB is a
      micromolecular database solution that supports exact, substructure, similarity,
      and combined searching. This solution is mainly implemented using scripting
      language Python with a web-based interface for compound management and searching.
      Almost all the searches are in essence done with pure SQL on the database by
      using the high performance of the database engine. Thus, impressive searching
      speed has been archived in large data sets for no external Central Processing
      Unit (CPU) consuming languages were involved in the key procedure of the
      searching. AVAILABILITY: MyMolDB is an open-source software and can be modified
      and/or redistributed under GNU General Public License version 3 published by the
      Free Software Foundation (Free Software Foundation Inc. The GNU General Public
      License, Version 3, 2007. Available at: http://www.gnu.org/licenses/gpl.html).
      The software itself can be found at http://code.google.com/p/mymoldb/.

PMID- 21728181
TI  - A high-sensitivity UPLC-MS/MS method for simultaneous determination and
      confirmation of triptolide in zebrafish embryos.
AB  - A high-sensitivity ultra-performance liquid-chromatography (UPLC) coupled with
      tandem mass spectrometric method was developed for simultaneous quantification
      and confirmation of triptolide in both zebrafish embryos and the aqueous-exposure
      solution on a tandem quadrupole mass spectrometer (TQ-MS). This was achieved by
      performing quantification using the multiple reaction monitoring (MRM)
      acquisition with simultaneous characterization of the MRM peak using product ion
      confirmation (PIC) acquisition as it elutes from the chromatographic system.
      Separation was achieved on a 1.7 um C(18) UPLC column using 0.1% formic acid
      water-acetonitrile mobile phase with a cycle time of 6 min. The linear range of
      0.115-360 ng/mL, and lower limits of detection of 0.02 ng/mL and quantification
      of 0.064 ng/mL were established. This method was successfully applied to
      determine the time course of triptolide absorption by zebrafish embryos and the
      amount of triptolide remaining in the culture medium after administration of two
      triptolide dosages at three time points. This coupled MRM with PIC approach could
      provide both qualitative and quantitative results without the need for repetitive
      analyses. This resulted in the reduction of further confirmative experiments and
      analytical time, and ultimately increased laboratory productivity.

PMID- 21728182
TI  - Effects of neferine on the pharmacokinetics of amiodarone in rats.
AB  - Amiodarone, an iodinated benzofuran derivative with predominantly class III anti
      arrhythmic effects, is used to treat supraventricular and ventricular
      arrhythmias. The purpose of this study was to assess the potential of neferine,
      an effective anti-pulmonary fibrosis drug isolated from the embryo of Nelumbo
      nucifera Gaertner's seeds, to alter the pharmacokinetic profile of amiodarone.
      Experimental Sprague-Dawley rats were randomly divided into two groups. In groups
      1 and 2, amiodarone was given to rats by intragastric and intravenous
      administration, respectively, while neferine was co-administratered by
      intragastric administration. Blood samples were collected from the orbital venous
      plexus at indicated time points and were analyzed for amiodarone concentration
      using RP-HPLC. The geometric mean ratio for C(max) and AUC(0-96) was calculated.
      There were no significant differences between the pharmacokinetics parameters of
      amiodarone administered intravenously or intragastrically and the control
      (without neferine) group (with ratios of 0.7-1.4 in all experimental groups),
      suggesting that neferine had no effect on amiodarone plasma pharmacokinetics. The
      dosage regimen of amiodarone does not need to be taken into consideration when
      combined with neferine.

PMID- 21728183
TI  - Mixed treatment comparison of repeated measurements of a continuous endpoint: an
      example using topical treatments for primary open-angle glaucoma and ocular
      hypertension.
AB  - Mixed treatment comparison (MTC) meta-analyses estimate relative treatment
      effects from networks of evidence while preserving randomisation. We extend the
      MTC framework to allow for repeated measurements of a continuous endpoint that
      varies over time. We used, as a case study, a systematic review and meta-analysis
      of intraocular pressure (IOP) measurements from randomised controlled trials
      evaluating topical ocular hypotensives in primary open-angle glaucoma or ocular
      hypertension because IOP varies over the day and over the treatment course, and
      repeated measurements are frequently reported. We adopted models for conducting
      MTC in WinBUGS (The BUGS Project, Cambridge, UK) to allow for repeated IOP
      measurements and to impute missing standard deviations of the raw data using the
      predictive distribution from observations with standard deviations. A flexible
      model with an unconstrained baseline for IOP variations over time and time
      invariant random treatment effects fitted the data well. We also adopted repeated
      measures models to allow for class effects; assuming treatment effects to be
      exchangeable within classes slightly improved model fit but could bias estimated
      treatment effects if exchangeability assumptions were not valid. We enabled all
      timepoints to be included in the analysis, allowing for repeated measures to
      increase precision around treatment effects and avoid bias associated with
      selecting timepoints for meta-analysis.The methods we developed for modelling
      repeated measures and allowing for missing data may be adapted for use in other
      MTC meta-analyses.

PMID- 21728184
TI  - A randomized controlled trial of a Functioning Improvement Tool home-visit
      program and its effect on cognitive function in older persons.
AB  - OBJECTIVE: The aim was to determine whether mini mental state examination (MMSE)
      scores improved in older participants of a Functioning Improvement Tool (FIT)
      home-visit program. METHODS: Two hundred fifty-two participants aged 65 years or
      older living at home and receiving preventive services or a community long-term
      care prevention project according to the Japanese social long-term care insurance
      system were enrolled and randomly assigned to an intervention group (n = 128) or
      a control group (n = 124). Intervention group subjects received a 60-min FIT home
      visit program for 3 months, which included guidance, assistance, and help in
      writing and teaching calculation in order to complete the FIT. Control subjects
      did not receive any home visits. Cognitive function was evaluated by MMSE.
      Analysis of covariance was used to examine the effects of the FIT adjusting for
      baseline MMSE scores, age, and sex. RESULTS: Fifty-three subjects were excluded
      because of withdrawal, hospitalization, death, relocation, or missing data of
      MMSE; 199 subjects (60 men, 139 women; age 78.6 +/- 7.4 years) were analyzed. The
      baseline MMSE scores did not differ between the intervention and control groups
      (24.2 +/- 4.3 vs. 24.1 +/- 4.7, p = 0.90). After the study period, the change in
      the MMSE score was significantly better in the intervention group than in the
      control group (0.8 +/- 0.3 vs. -0.1 +/- 0.2, p = 0.04). Stratified analyses
      showed that the intervention strategy was most effective in subjects with mild
      cognitive decline, with baseline MMSE scores from 18 to 23 points (1.9 +/- 0.5
      vs. -0.1 +/- 2.8, p = 0.04). CONCLUSIONS: Our FIT home-visit program improved
      MMSE scores in older participants with mild cognitive decline.

PMID- 21728185
TI  - Measures of genotoxicity in Gulf war I veterans exposed to depleted uranium.
AB  - Exposure to depleted uranium (DU), an alpha-emitting heavy metal, has prompted
      the inclusion of markers of genotoxicity in the long-term medical surveillance of
      a cohort of DU-exposed Gulf War veterans followed since 1994. Using urine U (uU)
      concentration as the measure of U body burden, the cohort has been stratified
      into low-u (<0.10 MUg U/g creatinine) and high-u groups (>= 0.10 MUg U/g
      creatinine). Surveillance outcomes for this cohort have historically included
      markers of mutagenicity and clastogenicity, with past results showing generally
      nonsignificant differences between low- vs. high-U groups. However, mean
      hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutant frequencies (MFs)
      have been almost 50% higher in the high-U group. We report here results of a more
      comprehensive protocol performed in a 2009 evaluation of a subgroup (N = 35) of
      this cohort. Four biomarkers of genotoxicity [micronuclei (MN), chromosome
      aberrations, and MFs of HPRT and PIGA] were examined. There were no statistically
      significant differences in any outcome measure when results were compared between
      the low- vs. high-U groups. However, modeling of the HPRT MF results suggests a
      possible threshold effect for MFs occurring in the highest U exposed cohort
      members. Mutational spectral analysis of HPRT mutations is underway to clarify a
      potential clonal vs. a threshold uU effect to explain this observation. This
      study provides a comprehensive evaluation of a human population chronically
      exposed to DU and demonstrates a relatively weak genotoxic effect of the DU
      exposure. These results may explain the lack of clear epidemiologic evidence for
      U carcinogenicity in humans. Environ. Mol. Mutagen., 2011. (c) 2011 Wiley-Liss,
      Inc.

PMID- 21728186
TI  - In vitro evaluation of the genotoxic and cytotoxic effects of artesunate, an
      antimalarial drug, in human lymphocytes.
AB  - Artesunate is one of the main antimalarial drugs used in several countries. It is
      a semisynthetic compound derived from artemisinin, a substance extracted from the
      Chinese plant, Artemisia annua L. Despite the widespread use of artesunate as an
      antimalarial drug, there is a lack of data regarding its genotoxic effects in
      human lymphocytes. Therefore, in this study, we used the comet assay and
      micronucleus test to evaluate the possible genotoxic effects of artesunate in
      cultured human lymphocytes. In addition, cell death by necrosis and apoptosis was
      also assessed. Cells exposed to different concentrations of artesunate showed a
      significant concentration-dependent increase (P < 0.05) in DNA damage index and
      micronuclei frequency. A significant increase in the frequency of apoptotic and
      necrotic cells was also observed. Our results showed that artesunate is a
      genotoxic and cytotoxic compound in cultured human lymphocytes.

PMID- 21728187
TI  - Dense carbide/metal composite membranes for hydrogen separations without platinum
      group metals.

PMID- 21728188
TI  - Boundary lubricants with exceptionally low friction coefficients based on 2D
      close-packed phosphatidylcholine liposomes.

PMID- 21728189
TI  - Buckled, stretchable polypyrrole electrodes for battery applications.

PMID- 21728190
TI  - High-efficiency solution-processed small molecule electrophosphorescent organic
      light-emitting diodes.

PMID- 21728191
TI  - Control of graphene field-effect transistors by interfacial hydrophobic self
      assembled monolayers.

PMID- 21728192
TI  - Inking elastomeric stamps with micro-patterned, single layer graphene to create
      high-performance OFETs.

PMID- 21728193
TI  - Rapid construction of three-dimensional multilayered tissues with endothelial
      tube networks by the cell-accumulation technique.

PMID- 21728194
TI  - Macroscale elastomeric conductors generated from hydrothermally synthesized metal
      polymer hybrid nanocable sponges.

PMID- 21728197
TI  - Isolated supramolecular [Ru(bpy)3]-viologen-[Ru(bpy)3] complexes with trapped
      CB[7,8] and photoinduced electron-transfer study in nonaqueous solution.
AB  - The synthesis of two supramolecular diruthenium complexes, 1?CB[7] and 1?CB[8]
      (CB[n]=cucurbit[n]uril), which contain the respective host CB[7] and CB[8], were
      synthesized and isolated. In the case of host CB[8], the desired supramolecular
      complex was obtained by utilizing dihydroxynapthalene as a template during the
      synthesis. The (1)H NMR spectra, electrochemistry, and photochemistry of these
      supramolecular complexes were performed in nonaqueous solution. The results show
      that both CB[7,8] hosts mainly bind to the linker part in solution in
      acetonitrile. This binding also lowers the oxidation potential of the ruthenium
      metal center and hinders the quenching effect by the viologen moiety. It has also
      been shown that external methylviologen can be included into 1?CB[8]. Analysis
      with NMR spectroscopy, electrochemistry, and photochemistry clearly shows a
      viologen radical dimer formation between the bound viologen and free
      methylviologen, thereby showing that the unique abilities of the CB[8] host can
      be utilized even in nonaqueous solution.

PMID- 21728198
TI  - Design and synthesis of sphingomyelin-cholesterol conjugates and their formation
      of ordered membranes.
AB  - A lipid raft is a cholesterol (Chol)-rich microdomain floating in a sea of lipid
      bilayers. Although Chol is thought to interact preferentially with sphingolipids
      such as sphingomyelin (SM), rather than with glycerophospholipids, the origin of
      the specific interaction has remained unresolved, primarily because of the high
      mobility of lipid molecules and weak intermolecular interactions. In this study,
      we synthesized SM-Chol conjugates with functionally designed linker portions to
      restrain Chol mobility and examined their formation of ordered membranes by a
      detergent insolubility assay, fluorescence anisotropy experiments, and
      fluorescence-quenching assay. In all of the tests, membranes prepared from the
      conjugates showed properties of ordered domains comparable to a SM-Chol (1:1)
      membrane. To gain insight into the structure of bilayers composed from the
      conjugates, we performed molecular dynamics simulations with 64 molecules of the
      conjugates, which suggested that the conjugates form a stable bilayer structure
      by bending at the linker portion and, mostly, reproduce the hydrogen bonds
      between the SM and Chol portions. These results imply that the molecular
      recognition between SM and Chol in an ordered domain is essentially reproduced by
      the conjugated molecules and, thus, demonstrates that these conjugate molecules
      could potentially serve as molecular probes for understanding molecular
      recognition in lipid rafts.

PMID- 21728199
TI  - Formation of quaternary carbon centers by highly regioselective hydroformylation
      with catalytic amounts of a reversibly bound directing group.

PMID- 21728200
TI  - Imidazole to NHC rearrangements at molybdenum centers: an experimental and
      theoretical study.
AB  - Both manganese and rhenium complexes of the type [M(bipy)(CO)(3)(N-RIm)](+)
      (bipy=2,2'-bipyridine) undergo deprotonation of the central CH group of the N
      alkylimidazole (N-RIm) ligand when treated with a strong base. However, the
      outcome of the reaction is very different for either metal. For Mn, the addition
      of the equimolar amount of an acid to the product of the deprotonation affords an
      N-heterocyclic carbene (NHC) complex, whereas for Re, once the deprotonation of
      the central imidazole CH group has occurred, the bipy ligand undergoes a
      nucleophilic attack on an ortho carbon, affording the C-C coupling product. The
      extension of these studies to pseudo-octahedral [Mo(eta(3)-allyl)(bipy)(CO)(2)(N
      RIm)](+) complexes has allowed us to isolate cationic NHC complexes (Mn(I)-type
      behavior), as well as their neutral imidazol-2-yl precursors. Theoretical studies
      of the reaction mechanisms using DFT computations were carried out on the
      deprotonation of [Mn(bipy)(CO)(3)(N-PhIm)](+), [Re(bipy)(CO)(3) (N-MesIm)](+),
      and [Mo(eta(3)-C(4)H(7))(bipy)(CO)(2) (N-MesIm)](+) complexes (Mes=mesityl) at
      the B3LYP/6-31G(d) (LANL2DZ for Mn, Re, and Mo) level of theory. Our results
      explain why different products have been found experimentally for Mn, Mo, and Re
      complexes. For Re, the process leading to a C-C coupling product is clearly more
      favored than those forming an imidazol-2-yl product. In contrast, for Mn and Mo
      complexes, the lower stabilizing interaction between the central imidazole and
      ortho bipy C atoms, along with the higher lability of the ligands, make the
      formation of an NHC-type product kinetically more accessible, in good agreement
      with experimental findings.

PMID- 21728201
TI  - Straightforward uranium-catalyzed dehydration of primary amides to nitriles.

PMID- 21728202
TI  - Quercetin 3-rhamnoside exerts antiinfluenza A virus activity in mice.
AB  - Our previous report showed that quercetin 3-rhamnoside (Q3R) possessed antiviral
      activity against influenza A/WS/33 virus in vitro. The present study evaluated
      the effect of Q3R on influenza A/WS/33 virus infected mice. Mice orally treated
      with Q3R (6.25 mg/kg per dose) at 2 h before and once daily for 6 days after
      influenza virus infection showed significant decreases in weight loss, and
      decreased mortality. Lung virus titers of mice killed at 6 days after infection
      were about 2000 times lower than that of the placebo-treated control mice and
      about two times lower than that for the oseltamivir-treated mice. Furthermore,
      histological evaluation showed that administration of Q3R delayed the development
      and progression of pulmonary lesions. Therefore, Q3R could be an attractive lead
      for the development of antiviral agents against influenza virus.

PMID- 21728203
TI  - Protective effects of aucubin on H2O2-induced apoptosis in PC12 cells.
AB  - The present study investigated the neuroprotective effects of aucubin on hydrogen
      peroxide (H2O2)-induced apoptosis in PC12 cells. Exposure of PC12 cells to 0.25
      mm H2O2 induced a leakage of lactate dehydrogenase and decreased cell viability,
      as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
      In a dose over 0.1 mm, aucubin increased PC12 cellular viability and markedly
      attenuated H2O2-induced apoptotic cell death. Quantitation of apoptosis by flow
      cytometry indicated that aucubin inhibited H2O2-induced apoptosis in PC12 cells.
      Nuclear damage was alleviated by aucubin, as shown by Hoechst staining. In
      addition, the levels of malondialdehyde were reduced and the activity of
      superoxide dismutase, catalase and glutathione peroxidase was augmented in these
      cells. These results indicated that aucubin inhibited H2O2-induced apoptosis in
      PC12 cells through regulation of the endogenous oxidant-antioxidant balance. Our
      results suggest that aucubin is a potential protective agent for the treatment of
      oxidative-stress-induced neurodegenerative disease.

PMID- 21728204
TI  - Direct detection of a single evoked action potential with MRS in Lumbricus
      terrestris.
AB  - Functional MRI (fMRI) measures neural activity indirectly by detecting the signal
      change associated with the hemodynamic response following brain activation. In
      order to alleviate the temporal and spatial specificity problems associated with
      fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs)
      with MRI directly, but have thus far provided conflicting results. In this study,
      we used MR to detect axonal NMFs in the median giant fiber of the earthworm,
      Lumbricus terrestris, by examining the free induction decay (FID) with a sampling
      interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature
      and stimulated at the threshold of action potential generation. FIDs were
      acquired shortly after the stimulation, and simultaneous field potential
      recordings identified the presence or absence of single evoked action potentials.
      FIDs acquired when the stimulus did not evoke an action potential were summed as
      background. The phase of the background-subtracted FID exhibited a systematic
      change, with a peak phase difference of (-1.2 +/- 0.3) * 10(-5) radians occurring
      at a time corresponding to the timing of the action potential. In addition, we
      calculated the possible changes in the FID magnitude and phase caused by a
      simulated action potential using a volume conductor model. The measured phase
      difference matched the theoretical prediction well in both amplitude and temporal
      characteristics. This study provides the first evidence for the direct detection
      of a magnetic field from an evoked action potential using MR.

PMID- 21728205
TI  - Pubic bone injuries in primiparous women: magnetic resonance imaging in detection
      and differential diagnosis of structural injury.
AB  - OBJECTIVE: To evaluate the utility of magnetic resonance imaging (MRI) in
      diagnosing structural injury in primiparous women at risk for pelvic floor
      injury. METHODS: This was an observational study of 77 women who underwent 3T MRI
      after delivery. Women were operationally defined as high risk (n = 45) for
      levator ani muscle tears (risk factors: second-stage labor > 150 min or < 30 min,
      anal sphincter tear, forceps, maternal age > 35 years and birth weight > 4000 g)
      or low risk (n = 32): vaginally delivered without these risk factors (n = 12);
      delivered by Cesarean section after second-stage labor > 150 min (n = 14) or
      delivered by Cesarean section without labor (n = 6). All women were imaged using
      fluid-sensitive MRI sequences. Two musculoskeletal radiologists reviewed images
      for bone marrow edema, fracture, pubic symphysis measurements and levator ani
      tear. RESULTS: MRI showed pubic bone fractures in 38% of women at high risk for
      pelvic floor injury and in 13% of women at low risk for pelvic floor injury
      (chi(2) (3) = 9.27, P = 0.03). Levator ani muscle tears were present in 44% of
      the high-risk women and in 9% of the low-risk women (chi(2) (3) = 11.57, P =
      0.010). Bone marrow edema in the pubic bones was present in 61% of women studied
      across delivery categories. Complex patterns of injury included combinations of
      bone marrow edema, fractures, levator ani tears and pubic symphysis injuries. No
      MRI-documented injuries were present in 18% of women at high risk and 44% at low
      risk for pelvic floor injury (chi(2) (1) = 6.2, P = 0.013). CONCLUSIONS: Criteria
      identifying primiparous women at risk for pelvic floor injury can predict
      increased risk of bone and soft tissue changes at the pubic symphysis. Fluid
      sensitive MRI has utility for differential diagnosis of structural injury in
      postpartum women.

PMID- 21728206
TI  - Evaluation of the perianal muscular complex in the prenatal diagnosis of
      anorectal atresia in a high-risk population.
AB  - OBJECTIVES: To investigate whether sonographic identification of the fetal
      perianal muscular complex (PAMC) is of value in the prenatal detection of
      anorectal atresia in a high-risk population. METHODS: During an 8-year study
      period, a total of 189 pregnancies at high risk for fetal anorectal atresia were
      prospectively examined for the presence/absence of the PAMC on axial ultrasound
      views of the fetal perineum. The prenatal findings were confirmed postnatally or
      at the time of postmortem examination. RESULTS: The median gestational age at
      examination was 27 (range, 15-37) weeks. The PAMC was identified in 175 fetuses,
      all of which had a normal anorectal canal at the time of delivery or at
      postmortem examination. The PAMC was not identified prenatally in the 14
      remaining cases, and the anus was absent in 11 fetuses with anorectal atresia and
      in two with urorectal septum malformation sequence. There was one false-positive
      case, in which the anus was anatomically and functionally normal but ectopically
      located, opening into the vaginal vestibule. Among these 14 cases of anorectal
      malformation, prenatal dilatation of the distal bowel was seen in nine (64.3%)
      and intraluminal calcified meconium or enterolithiasis in five (35.7%). Overall,
      absent PAMC on prenatal sonography in this high-risk population had a sensitivity
      of 100%, specificity of 99%, true-positive rate of 93% and false-positive rate of
      7% for the diagnosis of anorectal atresia. CONCLUSIONS: In a high-risk
      population, the absence of PAMC seems to be a highly sensitive and specific
      sonographic marker for anorectal atresia. The role of routine sonographic
      identification of the PAMC at the second-trimester scan to screen for cases of
      isolated anal atresia remains to be determined.

PMID- 21728207
TI  - Elastography for differentiation of subchorionic hematoma and placenta previa.

PMID- 21728208
TI  - Single umbilical artery in twin pregnancies.
AB  - OBJECTIVE: Our purpose was to evaluate the antenatal incidence of single
      umbilical artery (SUA) in twin pregnancies according to chorionicity and to
      assess its relationship with outcome. METHODS: Consecutive twin pregnancies
      undergoing ultrasound evaluation at our institutions were included. A targeted
      sonographic evaluation of the umbilical cord and vessels was performed in all
      cases. Chorionicity was determined according to standard ultrasound criteria.
      RESULTS: A total of 174 twin pregnancies, 100 dichorionic (DC) and 74
      monochorionic (MC), were included in the study. An SUA was identified in 17
      (9.8%) pregnancies, and in 18 (5.2%) fetuses. No difference was found in the
      incidence of SUA in DC and MC twins. Among affected pregnancies, all but one DC
      twin pregnancy were discordant for SUA. Structural and/or chromosomal
      abnormalities were present in 27.8% of fetuses with SUA. The prevalence of small
      for-gestational-age fetuses and of discordant birth weight (> 20% discordance)
      was higher in the SUA group than in the rest of the population, although these
      differences were not statistically significant. Twin pairs discordant for SUA had
      significantly higher weight discordance than those with normal umbilical cords.
      The sonographic cross-sectional area of the SUA did not appear to show the
      typical adaptive dilatation usually seen in singleton pregnancies with SUA.
      CONCLUSIONS: The incidence of SUA in twins is higher than in singletons, with no
      difference between MC and DC twins. Intrapair discordance for SUA in identical
      twins provides evidence against an exclusively genetic origin of this anomaly.
      The apparent failure of compensatory dilatation of the umbilical artery in twins
      with SUA may explain in part the higher risk for fetal growth restriction in
      these cases.

PMID- 21728209
TI  - Prenatal diagnosis of fetal left ventricular non-compaction cardiomyopathy.
AB  - Isolated left ventricular non-compaction (LVNC) is a rare disorder, classified as
      a primary genetic cardiomyopathy by the American Heart Association or as an
      unclassified cardiomyopathy by the European Society of Cardiology Working Group
      on Myocardial and Pericardial Diseases. The key features are the prominent
      trabeculae and deep intratrabecular recesses resulting in thickened myocardium
      with the two layers consisting of compacted and non-compacted myocardium. These
      recesses are in continuity with the left ventricular cavity and are filled with
      blood without evidence of communication to the epicardial coronary artery system.
      We present a case of LVNC detected prenatally at 25 + 4 weeks of gestation.

PMID- 21728210
TI  - Fetal left modified myocardial performance index: technical refinements in
      obtaining pulsed-Doppler waveforms.
AB  - OBJECTIVE: To assess the influence of machine settings (wall motion filter (WMF),
      angle of insonation, Doppler aliasing) and phase of valve clicks on repeatability
      of measurement of the fetal left modified myocardial performance index (Mod-MPI).
      METHODS: Fetal left Mod-MPI was evaluated prospectively in 157 morphologically
      normal fetuses at 19-36 weeks' gestation. In a baseline cohort, a previously
      published technique and settings were used for measurement of Mod-MPI. In a
      second cohort, the influence of WMF, angle of insonation, Doppler aliasing and
      selection of the phase of the valve clicks on repeatability of measurement of Mod
      MPI was assessed. RESULTS: The intraclass correlation coefficient (ICC) for
      measurement repeatability in the baseline cohort was 0.22. Increase in WMF to 300
      Hz or 500 Hz was associated with an increase in ICC to 0.60 and 0.55,
      respectively. An angle of insonation of < 15 degrees  was associated with an
      increase in ICC to 0.79 and 0.78 at a WMF of 300 and 500 Hz, respectively. A WMF
      of 300 Hz, angle of insonation of < 15 degrees  and absence of aliasing was
      associated with an increase in ICC to 0.85 and 0.87 at the beginning and peak of
      the valve click, respectively. Mod-MPI ranged from 0.35 to 0.48. An increase in
      calculated MPI was associated with increasing WMF, selection of the beginning vs.
      peak of the valve clicks and increase in angle of insonation. The presence or
      absence of aliasing had no effect. CONCLUSIONS: Refinement of machine settings
      improves repeatability of Mod-MPI, as does selection of the peak of the valve
      click. We suggest a consensus be reached as to the precise measurement of MPI,
      but for the moment would suggest: WMF, 300 Hz; angle of insonation, < 15 degrees
      ; avoiding Doppler aliasing; and selection of valve click peak. Systematic
      variation in measurement of time intervals may be responsible for the widely
      varying published normal ranges for Mod-MPI.

PMID- 21728211
TI  - Workplace smoking ban effects on unhappy smokers.
AB  - Economists usually draw a distinction between smokers. They distinguish 'happy
      addicts' a la Becker-Murphy from 'unhappy addicts' who state that smoking is a
      mistake and call for some help to quit. When evaluating tobacco control policies,
      it might be important to distinguish their effects on those two types of
      population. Indeed, such policies are welfare improving only if they help unhappy
      addicts to quit. We investigate the effect of the French workplace smoking ban on
      a sample of presumably 'unhappy addicts', smokers who consult tobacco cessation
      services. We show that the ban caused an increase in the demand for such
      services, and that this increase was larger in cold and rainy areas. It also
      induced an increase in the percentage of successful attempts to quit. Workplace
      smoking bans might be welfare improving since they seem to help 'unhappy addicts'
      to reconcile their behavior with their preferences.

PMID- 21728212
TI  - Do French low-income GPs choose to work less?
AB  - In France, a significant number of General Practitioners (GPs) earn less than 1.5
      times the French minimum salary. Using a representative panel of self-employed
      GPs over the years 1993-2004, this paper tests whether these low-income GPs
      choose to work less than all other GPs or whether they are constrained to do so.
      The test is based on measuring reactions to positive and negative demand shocks.
      As low-income GPs do not increase activity in response to a positive demand shock
      but decrease activity in response to a negative demand shock, it appears that
      their low-income status is attributable to a strong preference for leisure.

PMID- 21728215
TI  - Fluorescent nanowires self-assembled through host-guest interactions in modified
      calcein.

PMID- 21728216
TI  - Expanding the enzyme toolbox for biocatalysis.

PMID- 21728217
TI  - Using a photoacid generator to switch the direction of electronic energy transfer
      in a molecular triad.

PMID- 21728218
TI  - Highly enantioselective [3+2] annulation of Morita-Baylis-Hillman adducts
      mediated by L-threonine-derived phosphines: synthesis of 3-spirocyclopentene-2
      oxindoles having two contiguous quaternary centers.

PMID- 21728219
TI  - Isolation of azomethine ylides and their complexes: iridium(III)-mediated
      cyclization of nitrone substrates containing alkynes.

PMID- 21728220
TI  - Photoinduced symmetry-breaking charge separation: the direction of the charge
      transfer.

PMID- 21728221
TI  - A stable derivative of the global minimum on the Si6H6 potential energy surface.

PMID- 21728222
TI  - A simple reducing approach using amine to give dual functional EuSe nanocrystals
      and morphological tuning.

PMID- 21728223
TI  - Younan Xia.

PMID- 21728224
TI  - Self-propelled microrockets to capture and isolate circulating tumor cells.

PMID- 21728225
TI  - Synthesis and structural characterization of 2'-fluoro-alpha-L-RNA-modified
      oligonucleotides.
AB  - We describe the synthesis and binding properties of oligonucleotides that contain
      one or more 2'-fluoro-alpha-L-RNA thymine monomer(s). Incorporation of 2'-fluoro
      alpha-L-RNA thymine into oligodeoxynucleotides decreased thermal binding
      stability slightly upon hybridization with complementary DNA and RNA with the
      smallest destabilization towards RNA. Thermodynamic data show that the duplex
      formation with 2'-fluoro-alpha-L-RNA nucleotides is enthalpically disfavored but
      entropically favored. 2'-Fluoro-alpha-L-RNA nucleotides exhibit very good base
      pairing specificity following Watson--Crick rules. The 2'-fluoro-alpha-L-RNA
      monomer was designed as a monocyclic mimic of the bicyclic alpha-L-LNA, and
      molecular modeling showed that this indeed is the case as the 2'-fluoro monomer
      adopts a C3'-endo/C2'-exo sugar pucker. Molecular modeling of modified duplexes
      show that the 2'-fluoro-alpha-L-RNA nucleotides partake in Watson--Crick base
      pairing and nucleobase stacking when incorporated in duplexes while the unnatural
      alpha-L-ribo configured geometry of the sugar is absorbed by changes in the sugar
      phosphate backbone torsion angles. The duplex behavior of our new nucleotide
      follows that of alpha-L-LNA, by and large.

PMID- 21728226
TI  - Facile construction of nanofibers as a functional template for surface boron
      coordination reaction.
AB  - A facile strategy to perform the boron coordination reaction on a template of
      nanofibers is developed. Peptides with phenylboronic acid tails (peptidyl boronic
      acids) are designed and prepared as building blocks that can self-assemble into
      nanofibers. After the addition of vicinal diol structural motifs to the self
      assembling system, matrix-assisted laser desorption-ionization time-of-flight
      mass spectrometry indicates that the boron coordination reaction occurs on the
      template of nanofibers, which results in the increase of the width and roughness
      of the nanofibers as demonstrated by transmission electron microscopy and atomic
      force microscopy measurements. Because the surface-bound vicinal diol structural
      motifs have an ability to form hydrogen bonds with the peptide segments on the
      nanofibers, which restrain and disturb the hydrogen-bonding interaction among the
      nanofibers, the network structure formed based on the entanglement of nanofibers
      via hydrogen-bonding interaction is destroyed, which leads to a gel-sol
      transition. The novel concept of post-self-assembly modification demonstrated
      here could lead to a new technique for using self-assembled nanostructures in the
      emerging fields of nanoscience and nanotechnology.

PMID- 21728227
TI  - Solution-liquid-solid synthesis of semiconductor nanowires using clusters as
      single-source precursors.
AB  - CdSe clusters react with liquid Bi- nanocatalysts to form one-dimensional CdSe
      nanowires in solution. The use of cluster precursors as compared to molecular
      precursors leads to a high local CdSe concentration, which favors the growth of
      nanowires with thin diameters and a narrow diameter distribution. 

PMID- 21728228
TI  - Modulation of electron tunneling in a nanoparticle array by sound waves: an
      avenue to high-speed, high-sensitivity sensors.
AB  - Using an electrostatic self-assembly process, metal nanoparticles are deposited
      on polyelectrolyte fibers such that the interparticle distance between the
      nanoparticles is comparable to the polyelectrolyte's molecular width. By
      modulating the dielectric properties of the interparticle polymer layer, a highly
      sensitive, reversible humidity sensor with an ultrafast response time of ~3 ms is
      demonstrated. The higher sensitivity at low humidity shows a conductivity
      increase by over two orders of magnitude in response to a change in relative
      humidity from 21 to 1%. 

PMID- 21728229
TI  - Efficient roll-on transfer technique for well-aligned organic nanofibers.
AB  - A transfer technique enabling efficient device integration of fragile organic
      nanostructures is presented. The technique is capable of transferring organic
      nanofibers to arbitrary substrates, the preservation of nanofiber morphology is
      demonstrated, and the optical properties are unaffected or even improved by the
      transfer. 

PMID- 21728230
TI  - Development and validation according to European Union Decision 2002/657/EC of an
      HPLC-DAD method for milk multi-residue analysis of penicillins and amphenicols
      based on dispersive extraction by QuEChERS in MSPD format.
AB  - A precise and reliable method for milk residue analysis regarding five
      penicillins and three amphenicols by HPLC-diode array detection has been
      developed herein. The chromatographic separation was performed using a mobile
      phase of CH3 COONH4 (0.05 M) and ACN delivered by gradient program on a
      Kinetex(TM) -C18 core-shell, 2.6 MUm column, starting at a volume ratio of 95:5
      and ending at 60:40 after 17 min, remaining stable for 3 more min. A modified
      matrix solid phase dispersion procedure was applied for the extraction and clean
      up procedure of antibiotics using a mixture of Strata by Phenomenex and QuEChERS
      as a sorbent. The method was validated at the respective 0.5* MRL, MRL and 1.5
      *MRL level for each compound. Results were quantitated against the internal
      standard paracetamol (2 ng/MUL) according to the matrix-matched approach. The
      method was validated in line with the EC guidelines as cited in the Decision
      2002/657/EC. The within-laboratory reproducibility, expressed as a RSD, never
      exceeded 16%. All decision limit (CCalpha) values lay in the range between 35.2
      and 56.3 MUg/kg and the corresponding results for detection capability (CCbeta)
      were 39.9 and 61.9 MUg/kg. Ruggedness was estimated according to the Youden
      approach. 

PMID- 21728231
TI  - Retention of beta blockers on native titania stationary phase.
AB  - In recent years, metal oxides such as titania have been commercially available as
      chromatographic beds that can potentially be used to achieve novel separations of
      polar compounds. For example beta blockers, which are more often encountered in
      environmental sciences, have a wide range of polarity, and their basic character
      leads to difficult sample treatment and separation on conventional silica-based
      sorbents. The contribution of titania to the selective analysis of nine beta
      blockers was evaluated in terms of retention mechanisms observed in hydrophilic
      interaction LC using acetonitrile/water mobile phases with various additives. The
      mobile phase additives enabled to control the beta blocker charge as well as the
      titania surface charge. Depending on their respective ionic state, various
      retention mechanisms were identified at low water contents (<40%), including
      mainly adsorption mixed with hydrophilic interaction LC partition, ion exchange
      and ion exclusion. An unexpected retention was also observed for high water
      content and high pH, changing the selectivity of the support. 

PMID- 21728232
TI  - Phosphoprotein electrophoresis in the presence of Fe(III) ions.
AB  - Preparation of affinity polyacrylamide gels containing immobilized Fe(III) ions
      for the separation of proteins exhibiting metal ion binding properties is
      described. The presented method enables uniform distribution of immobilized metal
      ions in the affinity part of the polyacrylamide separating gel. Affinity gels
      prepared by this way are suitable to follow the effect of different
      concentrations of metal ions immobilized in polyacrylamide gel on a protein
      electrophoretic behavior. Polyacrylamide gels containing immobilized Fe(III) ions
      were used to study the electrophoretic behavior of two model proteins differing
      in their phosphate group content: chicken ovalbumin and bovine alpha-casein. For
      the electrophoretic separation, both the native and the denaturating conditions
      were used. 

PMID- 21728233
TI  - Polysulfone/pyrene membranes: a new microwell assay platform for bioapplications.
AB  - The use of PSU-Py prepared by click chemistry as a platform in membrane-bottom
      microwell plates for oxidase and hydrolase/oxidase-based enzyme assays is
      studied. For the GOx assay, the postulated fluorescence mechanism is based on the
      consumption of glucose by dissolved oxygen and GOx in the microwell plates
      covered with the PSU-Py membrane. For the AG-GOx assay, maltose is used as AG
      substrate and hydrolyzed to glucose which is then oxidized by the GOx activity.
      It is shown that the PSU-Py membrane acts as a fluorescence indicator of the
      enzymatic reactions, and both GOx and AG/GOx enzyme assays are successfully
      applied for glucose, maltose and acorbose analysis in the range 0.125-2.0 * 10(
      3) M glucose, 0.05-0.5 * 10(-3) M maltose, and 0.0125-0.1 mg . mL(-1) acorbose,
      respectively.

PMID- 21728234
TI  - In vitro characterization of an electroactive carbon-nanotube-based nanofiber
      scaffold for tissue engineering.
AB  - In an effort to reduce organ replacement and enhance tissue repair, there has
      been a tremendous effort to create biomechanically optimized scaffolds for tissue
      engineering applications. In contrast, the development and characterization of
      electroactive scaffolds has attracted little attention. Consequently, the
      creation and characterization of a carbon nanotube based poly(lactic acid)
      nanofiber scaffold is described herein. After 28 d in physiological solution at
      37  degrees C, a change in the mass, chemical properties and polymer morphology
      is seen, while the mechanical properties and physical integrity are unaltered. No
      adverse cytotoxic affects are seen when mesenchymal stem cells are cultured in
      the presence of the scaffold. Taken together, these data auger well for
      electroactive tissue engineering.

PMID- 21728235
TI  - Covalent heparin modification of a polysulfone flat sheet membrane for selective
      removal of low-density lipoproteins: a simple and versatile method.
AB  - A simple, convenient and economical method for the heparinization of PSf
      membranes is described, with the aim of preparing an LDL adsorber for
      simultaneous LDL apheresis and hemodialysis. An atmospheric pressure glow
      discharge generator is used to activate the PSf membrane surface, with subsequent
      chemical binding of heparin in the presence of EDC and NHS. ATR-FTIR spectroscopy
      and XPS measurements confirm successful surface modification. The PSf-Hep
      membrane shows good blood compatibility, with a relatively low amount and normal
      morphology of adherent platelets. ELISA results indicate that the PSf-Hep
      membrane exhibits excellent selective affinity for LDL in single and binary
      protein solutions, suggesting potential applications in hemodialysis with
      simultaneous LDL removal.

PMID- 21728236
TI  - Size-controlled nanoassemblies based on cyclodextrin-modified dextrans.
AB  - Nanoassemblies formed by host/guest interactions between two polymers in aqueous
      media are studied. Two types of polymers with the same dextran backbone are
      modified with adamantyl or betaCD groups. The sizes of the spontaneously formed
      nanoassemblies depend on the betaCD:Ada ratio and on the total concentration and
      composition of the mixtures. The results can be rationalized by assuming a
      core/shell structure of the nanoassemblies, the core resulting from associative
      phase separation of the two polymers and being stabilized by an external shell
      made of Ada-grafted dextran and containing ions adsorbed from the solution.
      Hydrophobic compounds such as benzophenone can be incorporated efficiently
      without inducing changes in properties of the nanoassemblies.

PMID- 21728237
TI  - Functionalization of nanofibrillated cellulose with silver nanoclusters:
      fluorescence and antibacterial activity.
AB  - Native cellulose nanofibers are functionalized using luminescent metal
      nanoclusters to form a novel type of functional nanocellulose/nanocluster
      composite. Previously, various types of cellulose fibers have been functionalized
      with large, non-luminescent metal nanoparticles. Here, mechanically strong native
      cellulose nanofibers, also called nanofibrillatedcellulose (NFC),
      microfibrillatedcellulose (MFC) ornanocellulose, disintegrated from macroscopic
      cellulose pulp fibers are used as support for small and fluorescent silver
      nanoclusters. The functionalization occurs in a supramolecular manner, mediated
      by poly(methacrylic acid) that protects nanoclusters while it allows hydrogen
      bonding with cellulose, leading to composites with fluorescence and antibacterial
      activity.

PMID- 21728238
TI  - Truly nonionic polymer shells for the encapsulation of living cells.
AB  - Engineering surfaces of living cells with natural or synthetic compounds can
      mediate intercellular communication and provide a protective barrier from hostile
      agents. We report on truly nonionic hydrogen-bonded LbL coatings for cell surface
      engineering. These ultrathin, highly permeable polymer membranes are constructed
      on living cells without the cationic component typically employed to increase the
      stability of LbL coatings. Without the cytotoxic cationic PEI pre-layer, the
      viability of encapsulated cells drastically increases to 94%, in contrast to 20%
      viability in electrostatically-bonded LbL shells. Moreover, the long-term growth
      of encapsulated cells is not affected, thus facilitating efficient function of
      protected cells in hostile environment.

PMID- 21728241
TI  - Editorial: Synthetic Biology - applying new paradigms at the interface of
      fundamental research and innovation.

PMID- 21728244
TI  - Meeting report: 7th HIC/RPC Bioseparation conference.

PMID- 21728245
TI  - Bis(metallo) capsules based on two ionic diphosphines.
AB  - Self-assembly and characterization of heterodimeric diphosphine capsules formed
      by multiple ionic interactions are described. The first type of capsules is
      composed of one novel tetrasulfonato-xantphos ligand and one complementary
      tetraammonium calix[4]arene. Encapsulation of a transition metal is achieved by
      self-assembly of a rhodium complex containing the tetraanionic diphosphine ligand
      and a tetracationic calix[4]arene. The second type of capsules is composed of two
      oppositely charged diphosphine ligands: one tetrasulfonato-xantphos and one
      tetraammonium-diphosphine (of the xantphos-, DPEphos-, and 1,2
      bis(diphenylphosphino)ethane (dppe)-type). Bis(metallo) capsules, that is,
      simultaneous encapsulation of two different transition metals, are created by
      self-assembly of a palladium or platinum complex containing a tetracationic
      ligand and a rhodium complex containing a tetraanionic ligand. Diphosphine
      ligands with different flexibilities and shapes assemble into metallocapsules
      with a proper capsular structure, as is indicated by (1)H NMR and 1D-NOESY
      spectroscopy, ESIMS, and modeling studies.

PMID- 21728246
TI  - Synthesis of a titanium-containing Prussian-blue analogue with a well-defined
      cube structure and its thermal conversion into a nanoporous titanium-iron-based
      oxide.

PMID- 21728247
TI  - "Design" of boron-based compounds as pro-nucleophiles and co-catalysts for
      indium(I)-catalyzed allyl transfer to various Csp3-type electrophiles.
AB  - We have recently uncovered a general indium(I)-catalyzed method for allylations
      and propargylation of acetals and ketals with a water- and air-stable allyl
      boronate. By using a more reactive allyl borane, we have successfully extended
      this methodology to the more challenging C-C coupling with ethers. Herein, we
      report an improved methodology for the indium(I)-catalyzed allylation of acetals
      and ethers, through combination of the allyl boronate with a commercially
      available "hard" Lewis acid, B-methoxy-9-BBN (BBN=borabicyclo[3.3.1]nonane), as
      an effective co-catalyst. Significantly, our work highlights for the first time
      the correlation between the Lewis acidity of "electrophilic" boron-based
      compounds and their "nucleophilic" reactivity in Csp(3)-Csp(3) couplings,
      catalyzed by a "soft" low-oxidation main group metal. In addition, we also report
      several applications of these methodologies to the selective synthesis of various
      carbohydrate derivatives.

PMID- 21728248
TI  - Biorefining: heterogeneously catalyzed reactions of carbohydrates for the
      production of furfural and hydroxymethylfurfural.
AB  - Furfurals are important intermediates in the chemical industry. They are
      typically produced by homogeneous catalysis in aqueous solutions. However,
      heterogeneously catalyzed processes would be beneficial in view of the principles
      of green chemistry: the elimination of homogeneous mineral acids makes the
      reaction mixtures less corrosive, produces less waste, and facilitates easy
      separation and recovery of the catalyst. Finding an active and stable water
      tolerant solid acid catalyst still poses a challenge for the production of
      furfural (furan-2-carbaldehyde) and 5-(hydroxymethyl)-2-furaldehyde (HMF).
      Furfural is produced in the dehydration of xylose, and HMF is formed from glucose
      and fructose in the presence of an acidic catalyst. Bases are not active in
      dehydration reaction but do catalyze the isomerization of monosaccharides, which
      is favorable when using glucose as a raw material. In addition to the desired
      dehydration of monosaccharides, many undesired side reactions take place,
      reducing the selectivity and deactivating the catalyst. In addition, the catalyst
      properties play an important role in the selectivity. In this Review, catalytic
      conversion approaches are summarized, focusing on the heterogeneously catalyzed
      formation of furfural. The attractiveness of catalytic concepts is evaluated,
      keeping in mind productivity, sustainability, and environmental footprint.

PMID- 21728249
TI  - Designing photobioreactors based on living cells immobilized in silica gel for
      carbon dioxide mitigation.
AB  - Atmospheric carbon dioxide levels have been rising since the industrial
      revolution, with the most dramatic increase occurring since the end of World War
      II. Carbon dioxide is widely regarded as one of the major factors contributing to
      the greenhouse effect, which is of major concern in today's society because it
      leads to global warming. Photosynthesis is Nature's tool for combating elevated
      carbon dioxide levels. In essence, photosynthesis allows a cell to harvest solar
      energy and convert it into chemical energy through the assimilation of carbon
      dioxide and water. Therefore photosynthesis is regarded as an ideal way to
      harness the abundance of solar energy that reaches Earth and convert
      anthropologically generated carbon dioxide into useful carbohydrates, providing a
      much more sustainable energy source. This Minireview aims to tackle the idea of
      immobilizing photosynthetic unicellular organisms within inert silica frameworks,
      providing protection both to the fragile cells and to the external ecosystem, and
      to use this resultant living hybrid material in a photobioreactor. The viability
      and activity of various unicellular organisms are summarized alongside design
      issues of a photobioreactor based on living hybrid materials.

PMID- 21728250
TI  - A brief summary of carbon nanotubes science and technology: a health and safety
      perspective.
AB  - Engineered nanomaterials, particularly carbon nanotubes (CNTs), hold great
      promise for a variety of industrial, consumer, and biomedical applications, due
      to their outstanding and novel properties. Over the last two decades many
      different types of CNTs have been produced at the industrial scale. Therefore,
      the exposure risk to humans associated with such a mass scale production has also
      increased substantially. This has led to increased concerns about the potential
      adverse health effects that may be associated with human exposure to CNTs,
      predominantly because of to their size, their shape, and chemistry. CNTs are also
      intended for use in many biomedical applications, and therefore their
      biocompatibility, biodistribution, and fate needs to be carefully assessed. This
      Minireview intends to highlight the current state of the assessment of potential
      adverse human health effects possibly associated with CNT exposure, as well as
      the challenges related to and posed by CNT safety research. The importance of
      reliability and comparison within and between different studies, as regards the
      test systems employed, is discussed as well as many other essential aspects
      relative to CNT safety research, for example efficient and comprehensive
      characterization, are discussed in the view of an improvement in data collection.

PMID- 21728251
TI  - [The French are wary of their drugs].

PMID- 21728252
TI  - Management of ruptured retinal arterial macroaneurysm with intravitreal
      bevacizumab.
AB  - The authors report the management of a ruptured retinal arterial macroaneurysm
      and associated hemorrhages with intravitreal injections of bevacizumab. A 79-year
      old woman presented with a history of systemic arterial hypertension and a
      ruptured retinal arterial macroaneurysm with pre-retinal, intraretinal, and
      subretinal hemorrhages extending into the macula. Visual acuity at presentation
      was 20/400. The patient was treated with two intravitreal injections of
      bevacizumab at 4-week intervals. Steady clearing of the pre-retinal,
      intraretinal, and subretinal hemorrhages was observed with restoration of final
      visual acuity to 20/20 in the 12 months after the initial presentation. It
      appears that the novel application of intravitreal bevacizumab may be used in the
      treatment of ruptured retinal arterial macroaneurysm.

PMID- 21728253
TI  - Highlights of the new WHO Report on Newborn and Infant Hearing Screening and
      implications for developing countries.
AB  - The Report summarizes the outcome of a recent informal consultation convened by
      the World Health Organization (WHO) in 2009 pursuant to the 1995 resolution of
      the World Health Assembly (WHA) urging Member States to promote programs for
      early hearing detection in babies and infants. The consultation was geared
      towards reaching global consensus on key principles on this subject based on the
      experiences and contributions of leading experts from various world regions and
      across relevant disciplines. After reviewing the current evidence on early
      hearing detection in babies and infants the Report outlined guiding principles
      for action by Member States covering issues such as etiology, case definition of
      hearing impairment, options for screening, program implementation, cost
      effectiveness as well as policy and legislation. The need for context-specific
      adaptations of current practices in the developed world to facilitate the
      development of effective and culturally appropriate early hearing detection
      programs in developing countries was emphasized. The potential role of private
      public partnerships including non-governmental organizations in designing and
      implementing hearing screening programs was highlighted while recognizing the
      necessity to develop requisite support services for infants detected with hearing
      impairment. Overall, the Report is likely to stimulate greater interest and
      progress towards early hearing detection initiatives particularly in countries
      where necessary actions are yet to be taken to implement the WHA resolution.
      However, any effort in this direction must be backed by greater professional
      engagement, appropriate national policies and strong involvement of WHO regional
      offices in developing countries.

PMID- 21728254
TI  - [Postoperative correction of the methabolism of the single  lung after
      pulmonectomy].

PMID- 21728255
TI  - [Local medicamentous treatment of wounds].

PMID- 21728256
TI  - [Subtotal intestinal resection for the thrombosis of the initial  part of the
      superior mesenteric artery].

PMID- 21728257
TI  - For love of Eisner. Thomas Eisner (1929-2011).

PMID- 21728258
TI  - Retraction notice to: Modification of hectorite by organofunctionalization for
      use in removing U(VI) from aqueous media: thermodynamic approach.

PMID- 21728259
TI  - [Flu immunization in pregnant women: protection of mothers and children].

PMID- 21728260
TI  - [Encephalitis: the English point of view].

PMID- 21728261
TI  - [Artemether-lumefantrine: another choice for the treatment of malaria in pregnant
      women].

PMID- 21728262
TI  - Militarization of nursing in the war on terror: perspective by Jane Koziol
      Mclain, PHD, RN and Emma Davies, PHD.

PMID- 21728263
TI  - Militarization of nursing in the war on terror: perspective by Elizabeth
      Tornquist, MA.

PMID- 21728264
TI  - Militarization of nursing in the war on terror: perspective by Geraldine Gorman,
      RN, PHD.

PMID- 21728265
TI  - Going viral: the Pentagon takes on a new enemy: swine flu.

PMID- 21728266
TI  - Does football have a future? The N.F.L. and the concussion crisis.

PMID- 21728267
TI  - The peanut puzzle: could the conventional wisdom on children and allergies be
      wrong?

PMID- 21728268
TI  - Low immunoglobulin E response in gastroallergic anisakiasis could be associated
      with impaired expulsion of larvae.

PMID- 21728269
TI  - Benefit of post PCI medical checklist to improve adhering with best practice
      guidelines in the patients with coronary artery disease undergoing percutaneous
      coronary intervention (PCI).
AB  - OBJECTIVE: To evaluate the effectiveness of medical and health education
      checklist according to ACC/AHA guidelines for improving compliance in the
      patients with coronary heart disease who underwent percutanoeus coronary
      intervention (PCI). MATERIAL AND METHOD: This study was a prospective cohort
      study between control group (historical coronary artery disease (CAD) cases who
      underwent PCI between October 2008 and May 2009) and a case group (CAD cases who
      underwent PCI between May 2009 and January 2010) at Her Majesty Cardiac Center
      floor 8th and Cardiac Care Unit, Faculty of Medicine, Siriraj Hospital, Mahidol
      University. In the control group, basic care proceed. In the case group, usual
      cares plus medical and health educational checklists proceed at 24 hours Post
      PCI, before discharge and at 6 months follow-up at PCI clinic. RESULTS: The study
      consisted of 160 patients, 79 patients in the control group and 81 patients in
      the case group. In the case group, patient received more frequent use of in
      hospital ACE-I (100% vs. 72%, p < 0.001), beta blockers (100% vs. 61.5%, p <
      0.001). At 6 month follow-up, the use of ACE-I (100% vs. 84.6%, p < 0.001) and
      beta blockers (100% vs. 82.1%, p < 0.001), remain higher in the case group.
      Comparing case group and control group,using the applied post PCI medical
      checklist correlated with more frequent use of in hospital angiotensin-converting
      enzyme inhibitors (100% vs. 71.8%, p < 0.001), beta blockers (100% vs. 61.5%, p <
      0.001). When looking at the quality of care indicators between two groups at 6
      month followup, the patients with DM, CKD in the case group have better blood
      pressure control according to the guidelines (64.5% vs. 35.1%, p < 0.001). Six
      month readmission rates were higher in control group as compared to case group
      (12.7% versus 5.2%, p < 0.005). CONCLUSION: We found that applied medical and
      health educational checklists improve both adhering to the best practice
      guideline and clinical outcome in the patients with CAD underwent PCI.

PMID- 21728270
TI  - Early experience of catheter directed thrombolysis for acute limb ischemia of
      native vessels and bypass graft thrombosis in Thai patients.
AB  - OBJECTIVE: We assessed the efficacy and safety of catheter directed thrombolysis
      in the patients with acute limb ischemia who have been treated with catheter
      directed thrombolysis. BACKGROUND: From the ACC/AHA 2005 Practice Guidelines for
      the Management of Patients with Peripheral Arterial Disease, Catheter-based
      thrombolysis is an effective and beneficial therapy and is indicated for patients
      with acute limb ischemia (Rutherford categories I and IIa) of less than 14
      days'duration. To date, there is no data concerning such treatment in Thai
      patients. MATERIAL AND METHOD: We retrospectively reviewed data of 66 patients
      with acute limb ischemia who underwent catheter directed thrombolysis (CDT) at
      Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj
      Hospital between January 2005 and January 2010. RESULTS: Sites of target vessel
      for CDT were at vascular bypass graft thrombosis (59%) followed by the native
      vessels artery (41%). Overall technical success rate was 92%. Re-establishment of
      blood flow was successful from catheter only directed thrombolysis in 41 patients
      (65%). The other 22 patients needed additional mechanical thrombectomy. Five
      patients (8%) could not reestablish blood flow after catheter directed
      thrombolysis with mechanical thrombectomy and underwent bypass surgery. After
      successful CDT ulcer improvement occurred in 71.42%. ABI improved from 0.45 to
      0.93. Major bleeding complications occurred in 4 cases (6%), 1 case due to
      retroperitoneal bleeding and the other 3 cases due to hemorrhagic stroke (4.5%).
      The predictor for hemorrhagic stroke was being in the higher age group (72 +/-
      1.2 vs. 66.7 +/- 1.8, p = 0.02). CONCLUSION: Catheter directed thrombolysis for
      treatment of acute limb ischemia in native artery occlusion or bypass graft
      thrombosis in Thai population has a 92% success rate with an acceptable bleeding
      complication rate similar to prior published studies. However, the incidence of
      hemorrhagic stroke is higher in patients older than 70 years.

PMID- 21728271
TI  - Correlation between peripheral arterial disease and stage of chronic kidney
      disease.
AB  - BACKGROUND: Atherosclerotic disease is the most common disease in clinical
      practice. Risk factors for the disease include diabetes, hypertension,
      dyslipidemia, smoking and chronic kidney disease (CKD). However, few studies have
      reported the correlation between peripheral arterial disease (PAD) and stages of
      CKD. Ankle brachial index (ABI) is a non-invasive method for detecting PAD with
      high sensitivity and specificity. OBJECTIVE: We studied the prevalence of
      asymptomatic PAD in patients with each stage of CKD using ABI measurement.
      MATERIAL AND METHOD: We conducted a study of patients with CKD classified by the
      Kidney Disease Outcomes Quality Initiative classification (K/DOQI classification)
      who attended at outpatient clinics. The patients with symptomatic PAD will be
      excluded. The participants will be sent to ABI measurement for the diagnosis of
      PAD, defined as ABI less than 0.9 RESULTS: The total number of patients who had
      been enrolled in the study was 201; Male 55%. Mean age was 65.16 +/- 11.3 years.
      22.4% of the patients have ABI less than 0.9 which was associated with older age,
      being female, and having lower diastolic blood pressure (p = 0.002, < 0.001, <
      0.0001, respectively) . Diabetes and coronary artery disease were higher in
      patients with abnormal ABI but with no statistical significance. No difference in
      other risk factors, for example, hypertension, dyslipidemia and smoking, was
      detected. Abnormal ABI was frequently seen in the patients with more advanced CKD
      and mean ABI was lower in patients with more advanced CKD stage. The meanABI of
      stage 4 and 5 CKD patients was lower than that of stage 1 and 2 (p < 0.05).
      CONCLUSION: The prevalence of asymptomatic PAD increased with more advanced stage
      of CKD.

PMID- 21728272
TI  - Bronchodilator effect of Ipraterol on methacholine-induced bronchoconstriction in
      asthmatic patients.
AB  - BACKGROUND: The addition of ipratropium, a synthetic cholinergic antagonist, to
      beta2-agonist therapy provides an additive improvement in adult with acute severe
      asthma and COPD because of increased vagal tone in the airways. We asked whether
      ipratropium in combination with fenoterol (Ipraterol) improved pulmonary function
      in comparison with original Berodual. MATERIAL AND METHOD: In order to determine
      the effects of nebulized a single dose of Ipraterol, the study was conducted in a
      double-blind, randomized and crossover manner by comparing the effect of
      nebulized a single dose of Berodual on methacholine-induced bronchoconstriction.
      The study consisted of an 1-week run-in phase and two study visits separated by a
      washout period of 7 days. PATIENTS: We studied 20 patients who ranged from 18 to
      80 years of age and had mild to moderate persistent asthma. RESULTS: Nebulized
      Ipraterol provided a rapid onset of bronchodilation effect similar to nebulized
      Berodual within 5 minutes by significantly increasing FEV, from 1.19 L to 1.73 L
      (p < 0.001) and from 1.19 to 1.69 L (p = 0.0001), respectively. This effect of
      Ipraterol lasted as long (up to 6 hours) and was similar to that of Berodual. The
      absolute FEV1 values at 360 min after Ipraterol treatment was still higher than
      the baseline values. We also found that there were no significant differences in
      the degree of improvement in FEV1 and hypokalemia following treatment with
      Ipraterol and Berodual. CONCLUSION: Our data suggest that nebulized Ipraterol
      offers a statistically significant improvement in pulmonary function without
      significant systemic absorption causing hypokalemia, with the improvement being
      comparable to that achieved with nebulized Berodual.

PMID- 21728273
TI  - Relationship between ankle brachial index (ABI), high sensitivity C-reactive
      protein (hs-CRP) and initial disability level in acute ischemic stroke.
AB  - BACKGROUND: Relationship between high sensitivity C-reactive protein (hs-CRP),
      Ankle Brachial index (ABI), severity of atherosclerosis and risk of ischemic
      stroke has been well documented. Studies concerning the association of ABI, hs
      CRP and initial disability level in acute ischemic stroke are scarce. OBJECTIVE:
      This study aimed to investigate the relationship between hs-CRP, ABI and level of
      initial disability in acute stroke setting. MATERIAL AND METHOD: We conducted a
      prospective observational study in patients with acute ischemic stroke within 48
      hours of onset. Initial ABI, hs-CRP were measured. Disability level was assessed
      at admission and 3 months using the modified Rankin scale (mRS) and the National
      Institue of Health Stroke scale (NIHSS). Statistical analysis was performed using
      Pearson's correlation coefficient. RESULTS: This study included 36 patients with
      a mean +/-SD age of 67.8 +/- 9.3 years. Sixteen (44.4%) were male. Median NIHSS
      and mRS were 10 and 4 respectively. Correlation between initial ABI and hs-CRP
      was poor (r(s) = -0.11, p = 0.57). There was a significant negative relationship
      between ABI and mRS at 0 and 3 months with a correlation coefficient of -0.45 (p
      = 0.006) and -0.41 (p = 0.02), respectively. CONCLUSION: There was a significant
      inverse relationship between ABI and initial stroke disability. However,
      correlation coefficient indicated only fair agreement beyond chance. This
      findings suggest that ABI may be used as a clinical predictor of initial
      disability level in acute stroke.

PMID- 21728275
TI  - Context is key for sequence data.

PMID- 21728276
TI  - Assessing equitable access to urban green space: the role of engineered water
      infrastructure.
AB  - Urban green space and water features provide numerous social, environmental, and
      economic benefits, yet disparities often exist in their distribution and
      accessibility. This study examines the link between issues of environmental
      justice and urban water management to evaluate potential improvements in green
      space and surface water access through the revitalization of existing engineered
      water infrastructures, namely stormwater ponds. First, relative access to green
      space and water features were compared for residents of Tampa, Florida, and an
      inner-city community of Tampa (East Tampa). Although disparities were not found
      in overall accessibility between Tampa and East Tampa, inequalities were apparent
      when quality, diversity, and size of green spaces were considered. East Tampa
      residents had significantly less access to larger, more desirable spaces and
      water features. Second, this research explored approaches for improving
      accessibility to green space and natural water using three integrated stormwater
      management development scenarios. These scenarios highlighted the ability of
      enhanced water infrastructures to increase access equality at a variety of
      spatial scales. Ultimately, the "greening" of gray urban water infrastructures is
      advocated as a way to address environmental justice issues while also
      reconnecting residents with issues of urban water management.

PMID- 21728274
TI  - Abhorring the vacuum: use of Alzheimer's disease medications in frontotemporal
      dementia.
AB  - There is no dedicated therapy for frontotemporal dementia (FTD). In order to
      treat the often devastating behavioral disturbances that interfere with both
      normal social functioning and the ability of caregivers to provide needed
      support, off-label medication usage is frequent. In addition to antidepressant
      and antipsychotic medications, which afford some benefits, US FDA-approved
      treatments for Alzheimer's disease are often used, including both cholinesterase
      inhibitors and memantine. Here, we review the various clinical manifestations of
      FTD, a general approach to treatment and the goals of any potential therapies. We
      review all of the existing literature on the use of cholinesterase inhibitors and
      memantine in FTD. While cholinesterase inhibitors do not currently have a place
      in FTD treatment, memantine may be helpful, although the results of two placebo
      controlled trials with this agent are not yet available. Finally, we discuss our
      view that such approaches will probably become supplanted by rational,
      molecularly-based therapies currently in development.

PMID- 21728277
TI  - Structural consequences of ferroelectric nanolithography.
AB  - Domains of remnant polarization can be written into ferroelectrics with nanoscale
      precision using scanning probe nanolithography techniques such as piezoresponse
      force microscopy (PFM). Understanding the structural effects accompanying this
      process has been challenging due to the lack of appropriate structural
      characterization tools. Synchrotron X-ray nanodiffraction provides images of the
      domain structure written by PFM into an epitaxial Pb(Zr,Ti)O(3) thin film and
      simultaneously reveals structural effects arising from the writing process. A
      coherent scattering simulation including the superposition of the beams
      simultaneously diffracted by multiple mosaic blocks provides an excellent fit to
      the observed diffraction patterns. Domains in which the polarization is reversed
      from the as-grown state have a strain of up to 0.1% representing the
      piezoelectric response to unscreened surface charges. An additional X-ray
      microdiffraction study of the photon-energy dependence of the difference in
      diffracted intensity between opposite polarization states shows that this
      contrast has a crystallographic origin. The sign and magnitude of the intensity
      contrast between domains of opposite polarization are consistent with the
      polarization expected from PFM images and with the writing of domains through the
      entire thickness of the ferroelectric layer. The strain induced by writing
      provides a significant additional contribution to the increased free energy of
      the written domain state with respect to a uniformly polarized state.

PMID- 21728278
TI  - High efficiency dye-sensitized solar cells based on hierarchically structured
      nanotubes.
AB  - Dye-sensitized solar cells (DSSCs) based on hierarchically structured TiO(2)
      nanotubes prepared by a facile combination of two-step electrochemical
      anodization with a hydrothermal process exhibited remarkable performance.
      Vertically oriented, smooth TiO(2) nanotube arrays fabricated by a two-step
      anodic oxidation were subjected to hydrothermal treatment, thereby creating
      advantageous roughness on the TiO(2) nanotube surface (i.e., forming
      hierarchically structured nanotube arrays-nanoscopic tubes composed of a large
      number of nanoparticles on the surface) that led to an increased dye loading.
      Subsequently, these nanotubes were exploited to produce DSSCs in a backside
      illumination mode, yielding a significantly high power conversion efficiency, of
      7.12%, which was further increased to 7.75% upon exposure to O(2) plasma.

PMID- 21728279
TI  - Influencing attitudes toward carbon capture and sequestration: a social marketing
      approach.
AB  - Carbon capture and sequestration (CCS), while controversial, is seen as promising
      because it will allow the United States to continue using its vast fossil fuel
      resources in a carbon-constrained world. The public is an important stakeholder
      in the national debate about whether or not the U.S. should include CCS as a
      significant part of its climate change strategy. Understanding how to effectively
      engage with the public about CCS has become important in recent years, as
      interest in the technology has intensified. We argue that engagement efforts
      should be focused on places where CCS will first be deployed, i.e., places with
      many "energy veteran" (EV) citizens. We also argue that, in addition to
      information on CCS, messages with emotional appeal may be necessary in order to
      engage the public. In this paper we take a citizen-guided social marketing
      approach toward understanding how to (positively or negatively) influence EV
      citizens' attitudes toward CCS. We develop open-ended interview protocols, and a
      "CCS campaign activity", for Wyoming residents from Gillette and Rock Springs. We
      conclude that our participants believed expert-informed CCS messages, embedded
      within an emotionally self-referent (ESR) framework that was relevant to Wyoming,
      to be more persuasive than the expert messages alone. The appeal to core values
      of Wyomingites played a significant role in the citizen-guided CCS messages.

PMID- 21728280
TI  - Multielementary (Cd, Cu, Pb, Zn, Ni) Stable Isotopic Exchange Kinetic (SIEK)
      method to characterize polymetallic contaminations.
AB  - A new method is proposed to precisely and simultaneously quantify the
      exchangeable pool of metals in soils and to describe its reactivity at short- and
      long-term. It is based on multielementary Stable Isotopic Exchange Kinetics
      (multi-SIEK), first validated by a comparison between two monoelementary
      radioactive ((109)Cd*, (65)Zn*) IEK experiments, a mono- ((106)Cd) and multi-
      ((62)Ni, (65)Cu, (67)Zn, (106)Cd, (204)Pb) SIEK. These experiments were performed
      on a polluted soil located near the Zn smelter plant of Viviez (Lot watershed,
      France). The IEK results obtained for Cd and Zn were consistent across the
      experiments. (109)Cd*, (65)Zn* IEK, and multi-SIEK were then applied on 3 non-
      and moderate impacted soils that also provided consistent results for Cd and Zn.
      Within these experimental conditions, it can be concluded that no competition
      occurs between Cd, Zn, and the other metals during SIEK. Multi-SIEK results
      indicate that the isotopically exchangeable pool of Ni, Zn, and Cu are small
      (E(Ni), E(Zn), and E(Cu) values up to 17%) whatever the pollution degree of the
      soils considered in this study and whatever the duration of the interaction. On
      the contrary, Cd displays the highest E values (from 35% to 61% after 1 week),
      and E(Pb) displays a maximum value of 26% after 1 week. The multi-SIEK provides
      useful information on metal sources and reactivity relationship. Ni would be
      located in stable pedogenic phases according to its very low enrichment factor.
      The low E(Zn) and E(Cu) are consistent with location of Zn and Cu in stable
      phases coming from tailings erosion. Though Pb enrichments in soils may also be
      attributed to tailings particles, its larger exchangeable pool suggests that the
      Pb-bearing phases are more labile than those containing Zn and Cu. The high
      mobility of Cd in upstream soils indicates that it has been mostly emitted as
      reactive atmospheric particles during high temperature ore-treatment.

PMID- 21728282
TI  - Relativistic effects and gold site distributions: synthesis, structure, and
      bonding in a polar intermetallic Na6Cd16Au7.
AB  - Na(6)Cd(16)Au(7) has been synthesized via typical high-temperature reactions, and
      its structure refined by single crystal X-ray diffraction as cubic, Fm 3m, a =
      13.589(1) A, Z = 4. The structure consists of Cd(8) tetrahedral star (TS)
      building blocks that are face capped by six shared gold (Au2) vertexes and
      further diagonally bridged via Au1 to generate an orthogonal, three-dimensional
      framework [Cd(8)(Au2)(6/2)(Au1)(4/8)], an ordered ternary derivative of
      Mn(6)Th(23). Linear muffin-tin-orbital (LMTO)-atomic sphere approximation (ASA)
      electronic structure calculations indicate that Na(6)Cd(16)Au(7) is metallic and
      that ~76% of the total crystal orbital Hamilton populations (-ICOHP) originate
      from polar Cd-Au bonding with 18% more from fewer Cd-Cd contacts.
      Na(6)Cd(16)Au(7) (45 valence electron count (vec)) is isotypic with the older
      electron-richer Mg(6)Cu(16)Si(7) (56 vec) in which the atom types are switched
      and bonding characteristics among the network elements are altered considerably
      (Si for Au, Cu for Cd, Mg for Na). The earlier and more electronegative element
      Au now occupies the Si site, in accord with the larger relativistic bonding
      contributions from polar Cd-Au versus Cu-Si bonds with the neighboring Cd in the
      former Cu positions. Substantial electronic differences in partial densities-of
      states (PDOS) and COHP data for all atoms emphasize these. Strong contributions
      of nearby Au 5d(10) to bonding states without altering the formal vec are the
      likely origin of these effects.

PMID- 21728281
TI  - Multinozzle emitter arrays for nanoelectrospray mass spectrometry.
AB  - Mass spectrometry (MS) is the enabling technology for proteomics and
      metabolomics. However, dramatic improvements in both sensitivity and throughput
      are still required to achieve routine MS-based single cell proteomics and
      metabolomics. Here, we report the silicon-based monolithic multinozzle emitter
      array (MEA) and demonstrate its proof-of-principle applications in high
      sensitivity and high-throughput nanoelectrospray mass spectrometry. Our MEA
      consists of 96 identical 10-nozzle emitters in a circular array on a 3 in.
      silicon chip. The geometry and configuration of the emitters, the dimension and
      number of the nozzles, and the micropillar arrays embedded in the main channel
      can be systematically and precisely controlled during the microfabrication
      process. Combining electrostatic simulation and experimental testing, we
      demonstrated that sharpened-end geometry at the stem of the individual
      multinozzle emitter significantly enhanced the electric fields at its protruding
      nozzle tips, enabling sequential nanoelectrospray for the high-density emitter
      array. We showed that electrospray current of the multinozzle emitter at a given
      total flow rate was approximately proportional to the square root of the number
      of its spraying-nozzles, suggesting the capability of high MS sensitivity for
      multinozzle emitters. Using a conventional Z-spray mass spectrometer, we
      demonstrated reproducible MS detection of peptides and proteins for serial MEA
      emitters, achieving sensitivity and stability comparable to the commercial
      capillary emitters. Our robust silicon-based MEA chip opens up the possibility of
      a fully integrated microfluidic system for ultrahigh-sensitivity and ultrahigh
      throughput proteomics and metabolomics.

PMID- 21728283
TI  - 'Old' clusters with new function: oxidation catalysis by high oxidation state
      manganese and cerium/manganese clusters using O2 gas.
AB  - The family of polynuclear manganese clusters of formula
      [Mn(12)O(12)(O(2)CR)(16)(H(2)O)(4)] (R = Et, Ph, etc.) has been investigated in
      great detail over the years for their ability to function as single-molecule
      magnets (SMMs), but they have not been employed as oxidation catalysts. In the
      present report, the ability is described of these clusters to act as catalysts in
      the selective oxidation of benzyl alcohol to benzaldehyde using molecular O(2) as
      the primary oxidant and the nitroxyl radical TEMPO as a cocatalyst. A systematic
      investigation of Mn clusters varied in their R group, oxidation state, and size
      was conducted in order to realize the electronic requirements that will lead to
      the best catalytic activity. The best reactivity (>99%) was obtained when the
      catalyst was the mixed-metal cluster [CeMn(6)O(9)(O(2)CMe)(9)(NO(3))(H(2)O)(2)],
      which contains Ce(4+)Mn(4+)(6) ions; in this case, lower loadings of catalysts
      (cluster and TEMPO) are required and the reaction can proceed even without a
      solvent. In addition, it has been demonstrated that the high efficiency can be
      only achieved when both high oxidation Ce(4+) and Mn(4+) ions are present within
      the same cluster.

PMID- 21728284
TI  - Photophysical properties of charged cyclometalated Ir(III) complexes: a joint
      theoretical and experimental study.
AB  - The photophysical properties of a series of charged biscyclometalated
      [Ir(ppy)(2)(N^N)](1+) complexes, where ppyH is 2-phenylpyridine and N^N is 2,2'
      bipyridine (bpy), 6-phenyl-2,2'-bipyridine (pbpy), and 6,6'-diphenyl-2,2'
      bipyridine (dpbpy) for complexes 1, 2, and 3, respectively, have been
      investigated in detail. The photoluminescence performance in solution decreases
      from 1 to 3 upon attachment of phenyl groups to the ancillary ligand. The
      absorption spectra recorded over time suggest that complex 3 is less stable
      compared to complexes 1 and 2 likely due to a nucleophilic-assisted ancillary
      ligand-exchange reaction. To clarify this behavior, the temperature dependence of
      the experimental intrinsic deactivation rate constant, k(in) = 1/tau, has been
      investigated from 77 K to room temperature. Temperature-dependent studies show
      that nonemitting metal-centered (MC) states are accessible at room temperature
      for complex 3. The experimental results are interpreted with the help of
      theoretical calculations performed within the density functional theory (DFT)
      approach. Calculations suggest that attachment of a phenyl group to the ancillary
      ligand (2) promotes the temperature-independent deactivation pathways, whereas
      attachment of a second phenyl group (3) also makes the temperature-dependent ones
      accessible through population of nonradiative (3)MC excited states.

PMID- 21728285
TI  - On the decoupling of relaxation modes in a molecular liquid caused by isothermal
      introduction of 2 nm structural inhomogeneities.
AB  - To support a new interpretation of the origin of the dynamic heterogeneity
      observed pervasively in fragile liquids as they approach their glass transition
      temperatures T(g), we demonstrate that the introduction of ~2 nm structural
      inhomogeneities into a homogeneous glass former leads to a decoupling of
      diffusion from viscosity similar to that observed during the cooling of
      orthoterphenyl (OTP) below T(A,) where Arrhenius behavior is lost. Further, the
      decoupling effect grows stronger as temperature decreases (and viscosity
      increases). The liquid is cresol, and the ~2 nm inhomogeneities are cresol
      soluble asymmetric derivatized tetrasiloxy-based (polyhedral oligomeric
      silsesquioxane (POSS)) molecules. The decoupling is the phenomenon predicted by
      Onsager in discussing the approach to a liquid-liquid phase separation with
      decreasing temperature. In the present case the observations support the notion
      of a polyamorphic transition in fragile liquids that is hidden below the glass
      transition. A similar decoupling can be expected as a globular protein is
      dissolved in dilute aqueous solutions or in protic ionic liquids.

PMID- 21728286
TI  - NMR-NOE and MD simulation study on phospholipid membranes: dependence on membrane
      diameter and multiple time scale dynamics.
AB  - Motional correlation times between the hydrophilic and hydrophobic terminal
      groups in lipid membranes are studied over a wide range of curvatures using the
      solution-state (1)H NMR-nuclear Overhauser effect (NOE) and molecular dynamics
      (MD) simulation. To enable (1)H NMR-NOE measurements for large vesicles, the
      transient NOE method is combined with the spin-echo method, and is successfully
      applied to a micelle of 1-palmitoyl-lysophosphatidylcholine (PaLPC) with diameter
      of 5 nm and to vesicles of dipalmitoylphosphatidylcholine (DPPC) with diameters
      ranging from 30 to 800 nm. It is found that the NOE intensity increases with the
      diameter up to ~100 nm, and the model membrane is considered planar on the
      molecular level beyond ~100 nm. While the NOE between the hydrophilic terminal
      and hydrophobic terminal methyl groups is absent for the micelle, its intensity
      is comparable to that for the neighboring group for vesicles with larger
      diameters. The origin of NOE signals between distant sites is analyzed by MD
      simulations of PaLPC micelles and DPPC planar bilayers. The slow relaxation is
      shown to yield an observable NOE signal even for the hydrophilic and hydrophobic
      terminal sites. Since the information on distance and dynamics cannot be
      separated in the experimental NOE alone, the correlation time in large vesicles
      is determined by combining the experimental NOE intensity and MD-based distance
      distribution. For large vesicles, the correlation time is found to vary by 2
      orders of magnitude over the proton sites. This study shows that NOE provides
      dynamic information on large vesicles when combined with MD, which provides
      structural information.

PMID- 21728288
TI  - Aggregation of silica nanoparticles directed by adsorption of lysozyme.
AB  - The interaction of the globular protein lysozyme with silica nanoparticles of
      diameter 20 nm was studied in a pH range between the isoelectric points (IEPs) of
      silica and the protein (pH 3-11). The adsorption affinity and capacity of
      lysozyme on the silica particles is increasing progressively with pH, and the
      adsorbed protein induces bridging aggregation of the silica particles. Structural
      properties of the aggregates were studied as a function of pH at a fixed protein
      to-silica concentration ratio which corresponds to a surface concentration of
      protein well below a complete monolayer in the complete-binding regime at pH > 6.
      Sedimentation studies indicate the presence of compact aggregates at pH 4-6 and a
      loose flocculated network at pH 7-9, followed by a sharp decrease of aggregate
      size near the IEP of lysozyme. The structure of the bridged silica aggregates was
      studied by cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray
      scattering. The structure factor S(q) derived from the scattering profiles
      displays characteristic features of particles interacting by a short-range
      attractive potential and can be represented by the square-well Percus-Yevick
      potential model, with a potential depth not exceeding 3k(B)T.

PMID- 21728289
TI  - JBIR-56 and JBIR-57, 2(1H)-pyrazinones from a marine sponge-derived Streptomyces
      sp. SpD081030SC-03.
AB  - Strain SpD081030SC-03, representing a novel species of Streptomyces, was isolated
      from a marine sponge. Two 3,5,6-trisubstituted 2(1H)-pyrazinones, JBIR-56 (1) and
      JBIR-57 (2), were isolated from a culture of SpD081030SC-03. The planar
      structures of 1 and 2 were assigned on the basis of extensive NMR and MS
      analyses. In addition, analyses of the methylated derivative of 1 confirmed a
      3,5,6-trisubstituted 2(1H)-pyrazinone moiety. The absolute configurations of the
      amino acid residues were determined by application of Marfey's method. Because 1
      did not appear to comprise the normal connection of amino acid units, we
      confirmed its structure by the total synthesis of 1. Biosynthetically, 1 consists
      of a unique skeleton connected to the peptide chain at C-5 of the pyrazinone
      ring.

PMID- 21728290
TI  - Quantum dots for electro-optic devices.
AB  - We discuss the use of quantum dots (QDs) in electro-optic devices. The focus of
      the article is on key problems in this area: the electronic and optical
      properties of QDs, dispersing QDs in polymers and the requirements for both, and
      QDs and polymer composites in devices such as solar cells, light-emitting
      devices, and detectors. The accompanying article by Geyer et al. in this issue of
      ACS Nano demonstrates an excellent example of a detector device, which also
      points to future directions for research in this field.

PMID- 21728291
TI  - Preparation of peptide-functionalized gold nanoparticles using one pot EDC/sulfo
      NHS coupling.
AB  - Although carbodiimides and succinimides are broadly employed for the formation of
      amide bonds (i.e., in amino acid coupling), their use in the coupling of peptides
      to water-soluble carboxylic-terminated colloidal gold nanoparticles remains
      challenging. In this article, we present an optimization study for the successful
      coupling of the KPQPRPLS peptide to spherical and rodlike colloidal gold
      nanoparticles. We show that the concentration, reaction time, and chemical
      environment are all critical to achieving the formation of robust, peptide-coated
      colloidal nanoparticles. Agarose gel electrophoresis was used for the
      characterization of conjugates.

PMID- 21728292
TI  - Thiol-ene click reaction as a general route to functional trialkoxysilanes for
      surface coating applications.
AB  - Functionalized trialkoxysilanes are widely used to modify the surface properties
      of materials and devices. It will be shown that the photoinitiated radical-based
      thiol-ene "click" reaction provides a simple and efficient route to diverse
      trialkoxysilanes. A total of 15 trialkoxysilanes were synthesized by reacting
      either alkenes with 3-mercaptopropyltrialkoxysilane or thiols with
      allyltrialkoxysilanes in the presence of a photoinitiator. The functionalized
      trialkoxysilanes were obtained in quantitative to near-quantitative yields with
      high purity. The photochemical reactions can be run neat in standard borosilicate
      glassware using a low power 15-W blacklight. A wide range of functional groups is
      tolerated in this approach, and even complex alkenes click with the silane
      precursors. To demonstrate that these silanes can be used as surface coating
      agents, several were reacted with iron oxide superparamagnetic nanoparticles and
      the loadings quantified. The photoinitiated thiol-ene reaction thus offers a
      facile and efficient method for preparing surface-active functional
      trialkoxysilanes.

PMID- 21728293
TI  - Small heat shock protein as a multifunctional scaffold: integrated tumor
      targeting and caspase imaging within a single cage.
AB  - Protein cages have the potential to serve as biomaterials for the targeted
      therapeutic and imaging systems. As an effort to exploit small heat shock protein
      (Hsp) cages as multifunctional biomaterials, we demonstrate that chemically and
      genetically modified Hsp cages permeate the cells via cancer cell binding and
      subsequent endocytic internalization and can image caspase activity in the live
      cells. Moreover, we report here that these functional Hsp cages can be
      specifically accumulated to tumor tissues of tumor-bearing mice when administered
      intravenously through the lateral tail vein. These tumor-targeting properties
      could be explained by the prolonged in vivo circulation and enhanced permeability
      and retention (EPR) effect as well as the ligand-mediated binding to cancer
      cells. Furthermore, when combined with the caspase sensing ability, our Hsp cage
      allows us to monitor the therapeutic evaluation after anticancer drug treatment
      by imaging the caspase activity within tumors. Therefore, we demonstrate that the
      Hsp cages have multifunctional scaffolds amenable to genetic and chemical
      modifications without loss of the cagelike architecture and can be exploited as
      biomedical materials including drug or imaging agent carriers.

PMID- 21728294
TI  - Direct sub-micrometer patterning of nanostructured conducting polymer films via a
      low-energy infrared laser.
AB  - Despite the many attractive properties of conjugated polymers, their practical
      applications are often limited by the lack of a simple, scalable, and
      nondisruptive patterning method. Here, a direct, scalable, high-resolution
      patterning technique for conducting polymers is demonstrated that does not
      involve photoresists, masks, or postprocessing treatment. Complex, well-defined
      patterns down to sub-micrometer scales can be created from nanofibrous films of a
      wide variety of conducting polymers by photothermally welding the nanofibers
      using a low-energy infrared laser. The welding depth, structural robustness, and
      optical properties of the films are readily controlled. In addition, the
      electrical properties such as conductivity can be precisely tuned over a 7-order
      of magnitude range, while maintaining the characteristic tunable electronic
      properties in the nonwelded polyaniline regions.

PMID- 21728295
TI  - Large-scale similarity search profiling of ChEMBL compound data sets.
AB  - A large-scale similarity search investigation has been carried out on 266 well
      defined compound activity classes extracted from the ChEMBL database. The
      analysis was performed using two widely applied two-dimensional (2D) fingerprints
      that mark opposite ends of the current performance spectrum of these types of
      fingerprints, i.e., MACCS structural keys and the extended connectivity
      fingerprint with bond diameter four (ECFP4). For each fingerprint, three nearest
      neighbor search strategies were applied. On the basis of these search
      calculations, a similarity search profile of the ChEMBL database was generated.
      Overall, the fingerprint search campaign was surprisingly successful. In 203 of
      266 test cases (~76%), a compound recovery rate of at least 50% was observed with
      at least the better performing fingerprint and one search strategy. The
      similarity search profile also revealed several general trends. For example,
      fingerprint searching was often characterized by an early enrichment of active
      compounds in database selection sets. In addition, compound activity classes have
      been categorized according to different similarity search performance levels,
      which helps to put the results of benchmark calculations into perspective.
      Therefore, a compendium of activity classes falling into different search
      performance categories is provided. On the basis of our large-scale
      investigation, the performance range of state-of-the-art 2D fingerprinting has
      been delineated for compound data sets directed against a wide spectrum of
      pharmaceutical targets.

PMID- 21728296
TI  - Flueggines A and B, two new dimeric indolizidine alkaloids from Flueggea virosa.
AB  - Two unprecedented C,C-linked dimeric indolizidine alkaloids, flueggines A (1) and
      B (2), were isolated from the twigs and leaves of Flueggea virosa. The structures
      and absolute configurations were elucidated by means of NMR, single-crystal X-ray
      diffraction, and CD analyses. Compound 1 is the first example of Securinega
      alkaloids bearing an isoxazolidine ring, the plausible biogenetic pathway of
      which is also proposed. Compound 2 exhibited growth inhibitory activity against
      MCF-7 and MDA-MB-231 human breast cancer cells.

PMID- 21728297
TI  - Ru-catalyzed asymmetric hydrogenation of 3-oxoglutaric acid derivatives via
      solvent-assisted pinpoint recognition of carbonyls in close chemical propinquity.
AB  - Upon comparison of hydrogenation rates of various beta-ketocarboxylic acid
      derivatives, beta-ketoamides were found to be hydrogenated slightly faster than
      beta-ketoesters in EtOH in the presence of [RuCl(benzene)(S)-SunPhos]Cl at 70 
      degrees C with 20 bar of hydrogen. In THF these differences were so sharpened
      that beta-ketoamides were hydrogenated even faster than in EtOH while the esters
      were extremely slow. Based on these findings, a series of 3-oxoglutaric acid
      derived with ester and amide moieties on the two ends were hydrogenated to 3
      hydroxyl products with high enantioselectivities.

PMID- 21728298
TI  - Effects of substituents upon the P...N noncovalent interaction: the limits of its
      strength.
AB  - Previous work has documented the ability of the P atom to form a direct
      attractive noncovalent interaction with a N atom, based in large measure on the
      charge transfer from the N lone pair into the sigma* antibonding orbital of the P
      H that is turned away from the N atom. As the systems studied to date include
      only hydrides, the present work considers how substituents affect the interaction
      and examines whether P...N might compete with other attractive forces such as H
      bonds. It is found that the addition of electron-withdrawing substituents greatly
      strengthens the P...N interaction to the point where it exceeds that of the
      majority of H-bonds. The highest interaction energy occurs in the
      FH(2)P...N(CH(3))(3) complex, amounting to 11 kcal/mol. A breakdown of the
      individual forces involved attributes the stability of the interaction to
      approximately equal parts electrostatic and induction energy, with a smaller
      contribution from dispersion.

PMID- 21728299
TI  - Palladium-catalyzed cross-coupling of benzyl thioacetates and aryl halides.
AB  - A method for preparing benzyl aryl thioethers utilizing an in situ deprotection
      of benzyl thioacetates as an alternative to free thiols as starting materials has
      been developed and optimized. Good to excellent yields of diverse benzyl aryl
      thioethers are obtained with air-stable, odor-free, and easy to prepare
      thioesters. A one-pot protocol for forming benzyl aryl thioethers from a benzyl
      halide, potassium thioacetate, and an aryl bromide has also been demonstrated.

PMID- 21728300
TI  - Structure and thermodynamics of lipid bilayers on polyethylene glycol cushions:
      fact and fiction of PEG cushioned membranes.
AB  - In developing well hydrated polymer cushioned membranes, structural studies are
      often neglected. In this work, neutron and X-ray reflectivity studies reveal that
      hybrid bilayer/polyethylene glycol (PEG) systems created from mixtures of
      phospholipids and PEG conjugated lipopolymers do not yield a hydrated cushion
      beneath the bilayer unless the terminal ends of the lipopolymers are
      functionalized with reactive end groups and can covalently bind (tether) to the
      underlying support surface. While reactive PEG tethered systems yielded bilayers
      with near complete surface coverage, a bimodal distribution of heights with sub
      micrometer lateral dimensions was observed consisting of cushioned membrane
      domains and uncushioned regions in close proximity to the support. The membrane
      fraction cushioned by the hydrated polymer could be controlled by adjusting the
      molar ratio of lipopolymer in the bilayer. A general phase diagram based on the
      free energy of the various configurations is derived that qualitatively predicts
      the observed behavior and the resulting structure of such systems a priori. As
      further evidenced by ellipsometry, atomic force and fluorescence microscopy, the
      tethered system provides a simple means for fabricating small cushioned domains
      within a membrane.

PMID- 21728301
TI  - Total synthesis of a CD-ring: side-chain building block for preparing 17-epi
      calcitriol derivatives from the Hajos-Parrish dione.
AB  - An efficient synthesis of the key building block for 17-epi-calctriol from the
      Hajos-Parrish dione involving a sequence of diastereoselective transformation of
      the azulene core and the side-chain construction is presented.

PMID- 21728302
TI  - Kinetically controlled seeded growth synthesis of citrate-stabilized gold
      nanoparticles of up to 200 nm: size focusing versus Ostwald ripening.
AB  - Monodisperse citrate-stabilized gold nanoparticles with a uniform quasi-spherical
      shape of up to ~200 nm and a narrow size distribution were synthesized following
      a kinetically controlled seeded growth strategy via the reduction of HAuCl(4) by
      sodium citrate. The inhibition of any secondary nucleation during homogeneous
      growth was controlled by adjusting the reaction conditions: temperature, gold
      precursor to seed particle concentration, and pH. This method presents improved
      results regarding the traditional Frens method in several aspects: (i) it
      produces particles of higher monodispersity; (ii) it allows better control of the
      gold nanoparticle size and size distribution; and (iii) it leads to higher
      concentrations. Gold nanoparticles synthesized following this method can be
      further functionalized with a wide variety of molecules, hence this method
      appears to be a promising candidate for application in the fields of biomedicine,
      photonics, and electronics, among others.

PMID- 21728303
TI  - Limitation of time-of-flight resolution in the ultra high mass range.
AB  - In this work, we have examined the reason for the deterioration of resolution and
      mass accuracy of time-of-flight mass analyzers with increasing mass after the
      expansion-induced kinetic energy has been eliminated by collisional cooling in an
      ion guide. Theoretically, removing the expansion-induced kinetic energy by
      collisional cooling permits the ions to travel along the ion guide axes without
      significant deviation so that they can be injected into the analyzer in a well
      collimated ion beam with well-defined kinetic energy. If the ions can be injected
      into an orthogonal acceleration time-of-flight mass analyzer (oa-TOF) in this
      manner, high-resolution mass analysis can be obtained regardless of mass or m/z.
      Unfortunately, high resolution did not result. It is our contention that the
      effusive expansion out of the first ion guide yields dispersive axial ejection
      that reduces TOF resolving power with increasing mass not m/z.

PMID- 21728304
TI  - Pleckstrin homology-phospholipase C-delta1 interaction with phosphatidylinositol
      4,5-bisphosphate containing supported lipid bilayers monitored in situ with dual
      polarization interferometry.
AB  - We have determined the kinetics and affinity of binding of PH-PLCdelta(1) to the
      PIP(2) headgroup lipids using an optical surface-sensitive technique in a time
      resolved manner. The use of dual polarization interferometry to probe supported
      lipid bilayers (SLBs) of different compositions allowed determination of accurate
      affinity constants and a layer structure of the peptide binding to the model
      membrane platform. In addition, the platform enabled us to monitor the detailed
      adsorption kinetics characterized by a strong initial electrostatic attraction of
      the peptide to the SLB surface followed by rearrangement and loss of possibly
      clustered peptides upon specific binding to the phosphoinositide headgroup. These
      kinetics differed substantially from adsorption kinetics for nonspecific binding
      to similarly charged control SLBs.

PMID- 21728305
TI  - A bicontinuous mesophase geometry with hexagonal symmetry.
AB  - We report that a specific realization of Schwarz's triply periodic hexagonal
      minimal surface is isotropic with respect to the Doi-Ohta interface tensor and
      simultaneously has minimal packing and stretching frustration similar to those of
      the commonly found cubic bicontinuous mesophases. This hexagonal surface, of
      symmetry P6(3)/mmc with a lattice ratio of c/a = 0.832, is therefore a likely
      candidate geometry for self-assembled lipid/surfactant or copolymer mesophases.
      Furthermore, both the peak position ratios in its powder diffraction pattern and
      the elastic moduli closely resemble those of the cubic bicontinuous phases. We
      therefore argue that a genuine possibility of experimental misidentification
      exists.

PMID- 21728307
TI  - Minimally invasive surface-enhanced Raman scattering detection with depth
      profiles based on a surface-enhanced Raman scattering-active acupuncture needle.
AB  - To obtain depth profiles of surface-enhanced Raman scattering (SERS) information
      in living systems, a SERS-active needle was structured by acupuncture needles,
      gold nanoshells (GNSs), and polystyrene, which were used as carriers, SERS-active
      elements to be absorbed on the carriers, and coatings to protect the absorbed
      GNSs from being erased during insertion, respectively. The SERS-active needle is
      minimally invasive for entering and exiting the body. The interspaces between the
      GNSs became vessels to collect diffused fluids at different depths after a SERS
      active needle was inserted into an agarose gel, and the SERS intensity profile on
      the SERS-active needle coincided with the concentration profile of Nile Blue A
      (NBA) in the gel. SERS detection in vitro avoided the signal attenuation in gels,
      and the SERS detection at different spots of the SERS-active needle provided a
      depth profile of the NBA molecule in the gel. In vivo experiments of NBA and 6
      mercaptopurine confirmed that the SERS-active needle could collect fluids in
      living systems easily with minimal invasion and provide information about depth
      profiles of target molecules in tissues.

PMID- 21728306
TI  - CSAR benchmark exercise of 2010: selection of the protein-ligand complexes.
AB  - A major goal in drug design is the improvement of computational methods for
      docking and scoring. The Community Structure Activity Resource (CSAR) aims to
      collect available data from industry and academia which may be used for this
      purpose ( www.csardock.org ). Also, CSAR is charged with organizing community
      wide exercises based on the collected data. The first of these exercises was
      aimed to gauge the overall state of docking and scoring, using a large and
      diverse data set of protein-ligand complexes. Participants were asked to
      calculate the affinity of the complexes as provided and then recalculate with
      changes which may improve their specific method. This first data set was selected
      from existing PDB entries which had binding data (K(d) or K(i)) in Binding MOAD,
      augmented with entries from PDB bind. The final data set contains 343 diverse
      protein-ligand complexes and spans 14 pK(d). Sixteen proteins have three or more
      complexes in the data set, from which a user could start an inspection of
      congeneric series. Inherent experimental error limits the possible correlation
      between scores and measured affinity; Pearson R is limited to ~ 0.91 (Pearson R2
      0.83) when fitting to the data set without over parameterizing. Pearson R is
      limited to ~ 0.83(Pearson R2 ~ 0.70) when scoring the data set with a method
      trained on outside data [corrected]. The details of how the data set was
      initially selected, and the process by which it matured to better fit the needs
      of the community are presented. Many groups generously participated in improving
      the data set, and this underscores the value of a supportive, collaborative
      effort in moving our field forward.

PMID- 21728308
TI  - Protein labeling enhances aptamer selection by methods of kinetic capillary
      electrophoresis.
AB  - Methods of kinetic capillary electrophoresis (KCE) facilitate highly efficient
      selection of DNA aptamers for protein targets. The inability to detect native
      proteins at low concentrations in capillary electrophoresis creates, however, a
      significant obstacle for many important protein targets. Here we suggest that
      protein labeling with new Chromeo dyes can help to overcome this obstacle. By
      labeling a number of proteins with Chromeo P503, we show that the labeling
      procedure enables accurate detection of proteins in CE without significantly
      affecting their electrophoretic mobility or their ability to bind DNA. Moreover,
      Chromeo P503 does not appear to label the amino-groups of buffer components to a
      significant extent, making the labeling procedure compatible with a large number
      of selection and run buffers. Fluorescent labeling of protein targets with
      Chromeo dyes empowers selection of aptamers by KCE methods and promises to
      increase the rate at which aptamers for new targets are being developed and
      introduced in various applications.

PMID- 21728309
TI  - Transport of charged Aerosol OT inverse micelles in nonpolar liquids.
AB  - Surfactants such as Aerosol OT (AOT) are commonly used to stabilize and
      electrically charge nonpolar colloids in devices such as electronic ink displays.
      The electrical behavior of such devices is strongly influenced by the presence of
      charged inverse micelles, formed by excess surfactant that does not cover the
      particles. The presence of charged inverse micelles results in increased
      conductivity of the solution, affecting both the energy consumption of the device
      and its switching characteristics. In this work, we use transient current
      measurements to investigate the electrical properties of suspensions of the
      surfactant Aerosol OT in dodecane. No particles are added, to isolate the effect
      of excess surfactant. The measured currents upon application of a voltage step
      are found to be exponentially decaying, and can be described by an analytical
      model based on an equivalent electric circuit. This behavior is physically
      interpreted, first by the high generation rate of charged inverse micelles giving
      the suspension resistor like properties, and second by the buildup of layers of
      charged inverse micelles at both electrodes, acting as capacitors. The model
      explains the measurements over a large range of surfactant concentrations,
      applied voltages, and device thicknesses.

PMID- 21728311
TI  - Probing the early events associated with liquid ammonia pretreatment of native
      crystalline cellulose.
AB  - Various chemicals are being explored for catalyzing efficient lignocellulose
      deconstruction. In particular, when liquid ammonia is used to convert the
      naturally occurring cellulose crystalline phase I(beta), to cellulose III(I), the
      rearrangement of the hydrogen bond network in cellulose III(I) results in
      enhanced hydrolysis yields. We use molecular dynamics simulations to analyze the
      interaction between a cellulose I(beta) fibril and ammonia. Our simulations
      reveal that early structural changes in the fibril are driven by the rapid
      formation of an extended hydrogen bond network between the solvent-exposed
      surface chains and ammonia that precedes ammonia penetration into the fibril. The
      emergence of this hydrogen bond network causes relative shifting of the cellulose
      layers within the fibril that in turn leads to the formation of channels
      orthogonal to the (100) and (-100) fibril surfaces. The channels allow ammonia
      molecules to penetrate into the cellulose fibril. These findings provide avenues
      for improving existing chemical pretreatments to make them more effective and
      economical.

PMID- 21728310
TI  - Single-monomer formulation of polymerized polyethylene glycol diacrylate as a
      nonadsorptive material for microfluidics.
AB  - Nonspecific adsorption in microfluidic systems can deplete target molecules in
      solution and prevent analytes, especially those at low concentrations, from
      reaching the detector. Polydimethylsiloxane (PDMS) is a widely used material for
      microfluidics, but it is prone to nonspecific adsorption, necessitating complex
      chemical modification processes to address this issue. An alternative material to
      PDMS that does not require subsequent chemical modification is presented here.
      Poly(ethylene glycol) diacrylate (PEGDA) mixed with photoinitiator forms on
      exposure to ultraviolet (UV) radiation a polymer with inherent resistance to
      nonspecific adsorption. Optimization of the polymerized PEGDA (poly-PEGDA)
      formula imbues this material with some of the same properties, including optical
      clarity, water stability, and low background fluorescence, that make PDMS so
      popular. Poly-PEGDA demonstrates less nonspecific adsorption than PDMS over a
      range of concentrations of flowing fluorescently tagged bovine serum albumin
      solutions, and poly-PEGDA has greater resistance to permeation by small
      hydrophobic molecules than PDMS. Poly-PEGDA also exhibits long-term (hour scale)
      resistance to nonspecific adsorption compared to PDMS when exposed to a low (1
      MUg/mL) concentration of a model adsorptive protein. Electrophoretic separations
      of amino acids and proteins resulted in symmetrical peaks and theoretical plate
      counts as high as 4 * 10(5)/m. Poly-PEGDA, which displays resistance to
      nonspecific adsorption, could have broad use in small volume analysis and
      biomedical research.

PMID- 21728312
TI  - Hydrogenated/fluorinated catanionic surfactants as potential templates for
      nanostructure design.
AB  - The structure and physicochemical properties of the nanoparticles spontaneously
      formed within aqueous mixtures of the hydrogenated/fluorinated catanionic
      surfactant cetyltrimetylammonium perfluorooctanoate in the absence of counterions
      as a function of its concentration are investigated by a combined
      experimental/computational study at room temperature. Apparent molar volumes,
      isentropic apparent molar compressibilities, and dynamic light scattering
      measurements together with transmission and cryo-scanning electron as well as
      confocal laser microscopy images, and computational molecular dynamics
      simulations indicate that a variety of structures of different sizes coexist in
      solution with vesicles of ~160 nm diameter. Interestingly, the obtained
      nanostructures were observed to self-assemble from a random distribution of
      monomers in a time scale easily accessible by atomistic classical molecular
      dynamics simulations, allowing to provide a comprehensive structural and dynamic
      characterization of the surfactant molecules at atomic level within the different
      aggregates. Overall, it is demonstrated that the use of mixed fluorinated
      hydrogenated surfactant systems represents an easy strategy for the design of
      specific nanoscale structures. The detailed structural analysis provided in the
      present work is expected to be useful as a reference to guide the design of new
      nanoparticles based on different hydrogenated/fluorinated catanionic surfactants.

PMID- 21728313
TI  - Sulfur-substituted tetrahedranes.
AB  - The stable sulfur-substituted tetrahedrane derivatives 2-4 were synthesized by
      the reaction of tris(trimethylsilyl)tetrahedranyllithium 1 with diphenyl
      disulfide, bis(4-nitrophenyl) disulfide, and bis(2,4-dinitrophenyl) disulfide,
      respectively, and characterized by both NMR spectroscopy and X-ray
      crystallography. Phenylsulfonyltetrahedrane 5 was prepared by the reaction of 2
      and m-chloroperbenzoic acid. The UV-vis absorption spectra of 2-4 suggested an
      interaction of the sigma orbital of the tetrahedrane core and the lone-pair
      electrons on the sulfur atom, whereas no interaction for 5 was found. Thermal
      reactions of 2 and 5 are also reported; 2 underwent fragmentation into two
      acetylene molecules, whereas 5 gave the corresponding cyclobutadiene.

PMID- 21728314
TI  - pH-responsive hydrogel/liposome soft nanocomposites for tuning drug release.
AB  - A novel liposome/hydrogel soft nanocomposite was explored as a controlled drug
      delivery system. A P2VP-PAA-PnBMA biocompatible, pH-responsive triblock
      terpolymer was used as an injectable gelator, entrapping PC/Chol liposomes loaded
      with calcein as hydrophilic model drug. The composite hydrogel was formed in
      vitro through a pH-induced sol-gel transition by dialysis against buffer under
      physiological conditions and at polymer concentration as low as 1 wt %. Excellent
      control of the calcein release was achieved just by adjusting the gelator
      concentration; that is, from 1 to 1.5 wt %, the drug release period was
      significantly prolonged from 14 to 32 days.

PMID- 21728315
TI  - Conformational changes of trialanine induced by direct interactions between
      alanine residues and alcohols in binary mixtures of water with glycerol and
      ethanol.
AB  - Despite the increasing relevance of characterizing local conformational
      distributions in the unfolded state, an unambiguous description of the role that
      solvation and the addition of certain cosolvents play in altering this ensemble
      has yet to emerge. Alcohol cosolvents, and specifically glycerol, are known to
      act as protein stabilizers. The underlying mechanism of this effect is, however,
      still debated. Short alanine-based peptides provide a suitable model system for
      exploring the influence of cosolvents on backbone conformations, as ample
      experimental evidence now indicates that alanine does not exhibit a true
      statistical coil behavior but rather shows strong preference for sampling the
      polyproline II (PPII) region of the Ramachadran map when solvated in water. To
      explore the effect glycerol and ethanol cosolvents have on the conformational
      distribution of trialanine, we combined UV-CD and H NMR spectroscopies. The
      temperature dependence of the conformationally sensitive maximum dichroism
      (Deltaepsilon) and (3)J(H(alpha)H(N)) coupling constants of two amide protons (N-
      and C-terminal) was subjected to a global thermodynamic analysis based on simple
      two-state PPII<->beta models. Interestingly, our results show that even small
      admixtures of alcohol (5% v/v) considerably change the spectral parameters,
      Deltaepsilon(PPII) and Deltaepsilon(beta), as well as the enthalpic and entropic
      differences between the two states. For the central residue of trialanine in 5%
      glycerol, we obtained a gain in enthalpy favoring PPII of DeltaDeltaH(n) = -4.80
      kJ/mol and a compensating increase in entropy favoring the beta-strand of
      DeltaDeltaS(n) = -13.53[J/mol K]. This causes increases in -DeltaG and slight
      increases in PPII content. Further addition of alcohol, however, reverses the
      trend in that it causes a destabilization of the hydration shell and a shift
      toward beta-strand conformations. The combined manifold of DeltaH and DeltaS
      values obtained for the investigated binary mixtures and the pure aqueous solvent
      exhibits an excellent linear correlation, which reflects enthalpy-entropy
      compensation and a common transition temperature. The latter can be considered an
      indication of a weak binding between cosolvent and peptide. A comparison of
      infrared and Raman spectra of trialanine in water and in water-alcohol mixtures
      indeed reveals a close proximity between aliphatic side chains of alanine
      residues and alcohol molecules even for 5% (v/v) alcohol-water mixtures. Hence,
      our results provide the first experimental evidence for direct interactions
      between, e.g., glycerol and peptides in aqueous solutions, in line with the
      result of recent calculations by Vagenende et al. (Biochemistry 2009, 48, 11084
      11096) but at variance with preferential exclusion theories.

PMID- 21728316
TI  - Theory of gas hydrates: effect of the approximation of rigid water lattice.
AB  - One of the assumptions of the van der Waals and Platteeuw theory for gas hydrates
      is that the host water lattice is rigid and not distorted by the presence of
      guest molecules. In this work, we study the effect of this approximation on the
      triple-point lines of the gas hydrates. We calculate the triple-point lines of
      methane and ethane hydrates via Monte Carlo molecular simulations and compare the
      simulation results with the predictions of van der Waals and Platteeuw theory.
      Our study shows that even if the exact intermolecular potential between the guest
      molecules and water is known, the dissociation temperatures predicted by the
      theory are significantly higher. This has serious implications to the modeling of
      gas hydrate thermodynamics, and in spite of the several impressive efforts made
      toward obtaining an accurate description of intermolecular interactions in gas
      hydrates, the theory will suffer from the problem of robustness if the issue of
      movement of water molecules is not adequately addressed.

PMID- 21728317
TI  - Dendritic MRI contrast agents: an efficient prelabeling approach based on CuAAC.
AB  - The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) allows the efficient and
      complete functionalization of dendrimers with preformed Gd chelates (prelabeling)
      to give monodisperse macromolecular contrast agents (CAs) for magnetic resonance
      imaging (MRI). This monodispersity contrasts with the typical distribution of
      materials obtained by classical routes and facilitates the characterization and
      quality control demanded for clinical applications. The potential of a new family
      of PEG-dendritic CA based on a gallic acid-triethylene glycol (GATG) core
      functionalized with up to 27 Gd complexes has been explored in vitro and in vivo,
      showing contrast enhancements similar to those of Gadomer-17, which reveals them
      to be a promising platform for the development of CA for MRI.

PMID- 21728318
TI  - Enhanced photocurrent generation by photosynthetic bacterial reaction centers
      through molecular relays, light-harvesting complexes, and direct protein-gold
      interactions.
AB  - The utilization of proteins as nanodevices for solar cells, bioelectronics, and
      sensors generally necessitates the transfer of electrons to or from a conducting
      material. Here we report on efforts to maximize photocurrent generation by
      bacterial photosynthetic reaction center pigment-protein complexes (RCs)
      interfaced with a metal electrode. The possibility of adhering RCs to a bare gold
      electrode was investigated with a view to minimizing the distance for electron
      tunneling between the protein-embedded electron-transfer cofactors and the metal
      surface. Substantial photocurrents were achieved despite the absence of coating
      layers on the electrode or engineered linkers to achieve the oriented deposition
      of RCs on the surface. Comparison with SAM-covered gold electrodes indicating
      enhanced photocurrent densities was achieved because of the absence of an
      insulating layer between the photoactive pigments and the metal. Utilizing RCs
      surrounded by light-harvesting 1 complex resulted in higher photocurrents,
      surprisingly not due to enhanced photoabsorption but likely due to better surface
      coverage of uniformly oriented RC-LH1 complexes and the presence of a tetraheme
      cytochrome that could act as a connecting wire. The introduction of cytochrome-c
      (cyt-c) as a molecular relay also produced increases in current, probably by
      intercalating between the adhered RCs or RC-LH1 complexes and the electrode to
      mediate electron transfer. Varying the order in which components were introduced
      to the electrode indicated that dynamic rearrangements of RCs and cyt-c occurred
      at the bare metal surface. An upper limit for current generation could not be
      detected within the range of the illumination power available, with the maximum
      current density achieved by RC-LH1 complexes being on the order of 25 MUA/cm(2).
      High currents could be generated consecutively for several hours or days under
      ambient conditions.

PMID- 21728319
TI  - Nanosized silica modified with carboxylic acid as support for controlled release
      of herbicides.
AB  - Hexagonal mesoporous silica modified with carboxylic acid (SiAc) has been
      obtained by reaction between chloroacetic acid and 3-aminopropyltrimethoxysilane,
      which was immobilized on porous material by a sol-gel process in the presence of
      an n-dodecylamine template. SiAc was characterized by TG, FT-IR, (29)Si NMR,
      (13)C NMR, SEM, surface charge density, surface area and porous diameter, which
      proved that the carboxylic group was chemically bonded to an inorganic structure,
      and the material presented a nanometric structure with spheres <50 nm and porous
      diameter of 10 nm. Herbicides 2,4-D and picloram were anchored on SiAc porous gel
      to produce the materials named SiD and SiPi, respectively. The controlled release
      of picloram from the SiAc was less than that of 2,4-D. After 26 days of
      releasing, 4.43 * 10(-5) mol L(-1) of picloram was delivered by SiPi, and 5.0 *
      10(-5) L(-1) was released from the SiD in 30 days.

PMID- 21728320
TI  - Galacto-configured aminocyclitol phytoceramides are potent in vivo invariant
      natural killer T cell stimulators.
AB  - A new class of alpha-galactosylceramide (alphaGC) nonglycosidic analogues bearing
      galacto-configured aminocyclitols as sugar surrogates have been obtained. The
      aminocyclohexane having a hydroxyl substitution pattern similar to an alpha
      galactoside is efficiently obtained by a sequence involving Evans aldol reaction
      and ring-closing metathesis with a Grubbs catalyst to give a key intermediate
      cyclohexene, which has been converted in galacto-aminocyclohexanes that are
      linked through a secondary amine to a phytoceramide lipid having a cerotyl N-acyl
      group. Natural Killer T (NKT) cellular assays have resulted in the identification
      of an active compound, HS161, which has been found to promote NKT cell expansion
      in vitro in a similar fashion but more weakly than alphaGC. This compound
      stimulates the release of Interferon-gamma (IFNgamma) and Interleukin-4 (IL-4) in
      iNKT cell culture but with lower potency than alphaGC. The activation of
      Invariant Natural Killer T (iNKT) cells by this compound has been confirmed in
      flow cytometry experiments. Remarkably, when tested in mice, HS161 selectively
      induces a very strong production of IFN-gamma indicative of a potent Th1 cytokine
      profile. Overall, these data confirm the agonist activity of alphaGC lipid
      analogues having charged amino-substituted polar heads and their capacity to
      modulate the response arising from iNKT cell activation in vivo.

PMID- 21728321
TI  - A theoretical study on the enhancement of functionally relevant electron
      transfers in biomimetic models of [FeFe]-hydrogenases.
AB  - Recent advances aimed at modeling the chemistry of the active site of [FeFe]
      hydrogenases (the H-cluster, composed by a catalytic Fe(2)S(2) subcluster and an
      Fe(4)S(4) portion) have led to the synthesis of binuclear coordination compounds
      containing a noninnocent organophosphine ligand [2,3-bis(diphenylphosphino)maleic
      anhydride, bma] that is able to undergo monoelectron reduction, analogously to
      the tetranuclear Fe(4)S(4) subcluster portion of the H-cluster. However, such a
      synthetic model was shown to feature negligible electronic communication between
      the noninnocent ligand and the remaining portion of the cluster, at variance with
      the enzyme active site. Here, we report a theoretical investigation that shows
      why the electron transfer observed in the enzyme upon protonation of the
      catalytic Fe(2)S(2) subsite cannot take place in the bma-containing cluster. In
      addition, we show that targeted modifications of the bma ligand are sufficient to
      restore the electronic communication within the model, such that electron density
      can be more easily withdrawn from the noninnocent ligand, as a result of
      protonation of the iron centers. Similar results were also obtained with a ligand
      derived from cobaltocene. The relevance of our findings is discussed from the
      perspective of biomimetic reproduction of proton reduction to yield molecular
      hydrogen.

PMID- 21728323
TI  - Higher oxidation states of americium: preparation, characterization and use for
      separations.

PMID- 21728322
TI  - Carbon nanotube microwell array for sensitive electrochemiluminescent detection
      of cancer biomarker proteins.
AB  - This paper describes fabrication of a novel electrochemiluminescence (ECL)
      immunosensor array featuring capture-antibody-decorated single-wall carbon
      nanotube (SWCNT) forests residing in the bottoms of 10-MUL wells with hydrophobic
      polymer walls. Silica nanoparticles containing [Ru(bpy)(3)](2+) and secondary
      antibodies (RuBPY-silica-Ab(2)) are employed in this system for highly sensitive
      two-analyte detection. Antibodies to prostate specific antigen (PSA) and
      interleukin-6 (IL-6) were attached to the same RuBPY-silica-Ab(2) particle. The
      array was fabricated by forming the wells on a conductive pyrolytic graphite chip
      (1 in. * 1 in.) with a single connection to a potentiostat to achieve ECL. The
      sandwich immunoassay protocol employs antibodies attached to SWCNTs in the wells
      to capture analyte proteins. Then RuBPY-silica-Ab(2) is added to bind to the
      captured proteins. ECL is initiated in the microwells by electrochemical
      oxidation of tripropyl amine (TprA), which generates excited state
      [Ru(bpy)(3)](2+) in the 100-nm particles, and is measured with a charge-coupled
      device (CCD) camera. Separation of the analytical spots by the hydrophobic wall
      barriers enabled simultaneous immunoassays for two proteins in a single sample
      without cross-contamination. The detection limit (DL) for PSA was 1 pg mL(-1) and
      for IL-6 was 0.25 pg mL(-1) (IL-6) in serum. Array determinations of PSA and IL-6
      in patient serum were well-correlated with single-protein ELISAs. These microwell
      SWCNT immunoarrays provide a simple, sensitive approach to the detection of two
      or more proteins.

PMID- 21728324
TI  - Copper(I) thiocyanate-amine networks: synthesis, structure, and luminescence
      behavior.
AB  - A series of metal-organic networks of CuSCN were prepared by direct reactions
      with substituted pyridine and aliphatic amine ligands, L. Thiocyanate bridging is
      seen in all but 1 of 11 new X-ray structures. Structures are reported for
      (CuSCN)L sheets (L = 3-chloro- and 3-bromopyridine, N-methylmorpholine), ladders
      (L = 2-ethylpyridine, N-methylpiperidine), and chains (L = 2,4,6-collidine). X
      ray structures of (CuSCN)L(2) are chains (L = 4-ethyl- and 4-t-butylpyridine,
      piperidine, and morpholine). A unique N-thiocyanato monomer structure, (CuSCN)(3
      ethylpyridine)(3), is also reported. In most cases, amine ligands are thermally
      released at temperatures <100  degrees C. Strong yellow-to-green luminescence at
      ambient temperature is observed for the substituted pyridine complexes. High
      solid state quantum efficiencies are seen for many of the CuSCN-L complexes.
      Microsecond phosphorescence lifetimes seen for CuSCN-L are in direct contrast to
      the nanosecond-lifetime emission of CuSCN. MLCT associated with pyridine pi*
      orbitals is proposed as the excitation mechanism.

PMID- 21728325
TI  - Spin canting and metamagnetism in 2D and 3D cobalt(II) coordination networks with
      alternating double end-on and double end-to-end azido bridges.
AB  - By employing an N,N'-ditopic spacer 2-aminopyrazine (ampyz), two-dimensional (2D)
      (1) and three-dimensional (3D) (2) azido-bridged cobalt(II) coordination networks
      with the identical formula [Co(N(3))(2)(ampyz)](n) have been synthesized and
      characterized structurally and magnetically. Compound 1 was prepared by the layer
      diffusion method in ambient temperature and crystallized in the high symmetric
      space group Immm. The 2D square-grid structure of 1 contains the perfect
      symmetric linear of alternating double end-on (EO) and double end-to-end (EE)
      azido-bridged Co(II) chains which are linked together by an ampyz spacer in trans
      arrangement. The intralayer pi-pi stacking interactions among ampyz spacers
      additionally stabilize this layer. The adjacent 2D layers are assembled by the
      intermolecular hydrogen bonding between the NH(2) of the ampyz and the EE azido
      ligands building a 3D structure. Compound 2 was prepared by a hydrothermal
      technique and shows a 3D framework containing a zigzag chain of similarly
      alternating double EO and double EE azido-bridged Co(II) center. In contrast,
      this chain is linked by two ampyz spacers in cis-fashion giving rise to a 3D
      structure. The magnetic investigation of 1 shows the coexistence of a big spin
      canting angle and metamagnetism having magnetic ordering at 10 K, whereas the
      magnetic behavior of 2 simply exhibits spin-canted antiferromagnetism below T(N)
      of 16 K.

PMID- 21728326
TI  - Motion of liquid drops on surfaces induced by asymmetric vibration: role of
      contact angle hysteresis.
AB  - Hysteresis of wetting, like the Coulombic friction at solid/solid interface,
      impedes the motion of a liquid drop on a surface when subjected to an external
      field. Here, we present a counterintuitive example, where some amount of
      hysteresis enables a drop to move on a surface when it is subjected to a periodic
      but asymmetric vibration. Experiments show that a surface either with a
      negligible or high hysteresis is not conducive to any drop motion. Some finite
      hysteresis of contact angle is needed to break the periodic symmetry of the
      forcing function for the drift to occur. These experimental results are
      consistent with simulations, in which a drop is approximated as a linear harmonic
      oscillator. The experiment also sheds light on the effect of the drop size on
      flow reversal, where drops of different sizes move in opposite directions due to
      the difference in the phase of the oscillation of their center of mass.

PMID- 21728327
TI  - Functionalizing metal nanostructured film with graphene oxide for ultrasensitive
      detection of aromatic molecules by surface-enhanced Raman spectroscopy.
AB  - Surface-enhanced Raman spectroscopy (SERS) as a powerful analytical tool has
      gained extensive attention. Despite of many efforts in the design of SERS
      substrates, it remains a grand challenge for creating a general substrate that
      can detect diverse target analytes. Herein, we report our attempt to address this
      issue by constructing a novel metal-graphene oxide nanostructured film as SERS
      substrate. Taking advantages of the high affinity of graphene oxide (GO) toward
      aromatic molecules and the SERS property of nanostructured metal, this structure
      exhibits great potential for diverse aromatic molecules sensing, which is
      demonstrated by using crystal violet (CV) with positive charge, amaranth with
      negative charge, and neutral phosphorus triphenyl (PPh(3)) as model molecules.

PMID- 21728328
TI  - Fluoroalkyl-functionalized silica particles: synthesis, characterization, and
      wetting characteristics.
AB  - Fluoroalkyl-functionalized silica particles for use in nonwetting surfaces were
      prepared by treatment of silica particles with fluoroalkyl-functional
      chlorosilanes. Both fumed and precipitated silica were studied, as well as the
      efficiency of surface coverage using mono-, di-, and trifunctional chlorosilanes.
      The most effective surface treatment was accomplished via the surface grafting of
      monofunctional chlorosilanes in the presence of preadsorbed dimethylamine under
      anhydrous conditions at room temperature. Confirmation of covalent attachment was
      accomplished via Fourier transform infrared (FT-IR) spectroscopy, while elemental
      analysis, thermogravimetric analysis, and nitrogen adsorption isotherms were used
      to determine grafting densities and additional key geometric characteristics of
      the grafted layer. The effect of residual silanol content on the moisture uptake
      properties of the modified silica particles was determined by measuring the water
      uptake of unbound particles, while liquid wetting properties were determined by
      dynamic contact angle analysis of elastomeric composites. Although residual
      silanol content was shown to effect wetting properties, results suggest that
      surface geometry dominates the performance of liquid-repellent surfaces. The
      potential use of fluoroalkyl-functionalized silica particles for hydrophobic and
      oleophobic applications is discussed.

PMID- 21728329
TI  - Stepwise formation of a molecular square with bridging NH,O-substituted dicarbene
      building blocks.
AB  - The beta,beta'-bis(triisopropylsiloxy)phenyl-1,4-diisocyanide 3 and
      [Ir(Cp*)Cl(2)](2) were used for the stepwise assembly of the [Ir(Cp*)Cl] cornered
      molecular square [6](Cl)(4). Synthesis of the tetrakis(diisocyanide) bridged
      molecular square [Ir(Cp*)Cl(3)](4)(BF(4))(4) [5](BF(4))(4) followed by cleavage
      of the O-Si(i-Pr)(3) bonds of the diisocyanide bridges with HCl/i-PrOH led to an
      intramolecular attack of the liberated hydroxyl groups at the isocyanide carbon
      atoms with formation of molecular square [6](Cl)(4) featuring four dicarbene
      linkers.

PMID- 21728330
TI  - Predicting the migration rate of dialkyl organotins from PVC pipe into water.
AB  - Organotins (OTs) are additives widely used as thermal and light stabilizers in
      polyvinyl chloride (PVC) plastics. OTs can leach into water flowing through PVC
      pipes. This work examines the leaching rates of two potentially neurotoxic OTs,
      dimethyl tin (DMT) and dibutyl tin (DBT), from PVC pipe. Water was circulated in
      a closed loop laboratory PVC pipe system. Using a gas chromatograph-pulsed flame
      photometric detector (GC-PFPD), the change in concentrations of DMT and DBT in
      the water in the system was monitored over time and allowed to reach equilibrium.
      OT concentration as a function of time was analyzed using a mechanistic leaching
      rate model. The diffusion coefficient for OT in the PVC pipe material, the only
      unknown model parameter, was found to be 9 * 10(-18) m(2)/s. This value falls
      within with the range of values estimated from the literature (2 * 10(-18) to 2 *
      10(-17) m(2)/s) thus increasing confidence in the leaching rate model.

PMID- 21728331
TI  - Thermochemical property estimation of hydrogenated silicon clusters.
AB  - The thermochemical properties for selected hydrogenated silicon clusters
      (Si(x)H(y), x = 3-13, y = 0-18) were calculated using quantum chemical
      calculations and statistical thermodynamics. Standard enthalpy of formation at
      298 K and standard entropy and constant pressure heat capacity at various
      temperatures, i.e., 298-6000 K, were calculated for 162 hydrogenated silicon
      clusters using G3//B3LYP. The hydrogenated silicon clusters contained ten to
      twenty fused Si-Si bonds, i.e., bonds participating in more than one three- to
      six-membered ring. The hydrogenated silicon clusters in this study involved
      different degrees of hydrogenation, i.e., the ratio of hydrogen to silicon atoms
      varied widely depending on the size of the cluster and/or degree of
      multifunctionality. A group additivity database composed of atom-centered groups
      and ring corrections, as well as bond-centered groups, was created to predict
      thermochemical properties most accurately. For the training set molecules, the
      average absolute deviation (AAD) comparing the G3//B3LYP values to the values
      obtained from the revised group additivity database for standard enthalpy of
      formation and entropy at 298 K and constant pressure heat capacity at 500, 1000,
      and 1500 K were 3.2%, 1.9%, 0.40%, 0.43%, and 0.53%, respectively. Sensitivity
      analysis of the revised group additivity parameter database revealed that the
      group parameters were able to predict the thermochemical properties of molecules
      that were not used in the training set within an AAD of 3.8% for standard
      enthalpy of formation at 298 K.

PMID- 21728332
TI  - Preferential binding of a novel polyhistidine peptide dendrimer ligand on quantum
      dots probed by capillary electrophoresis.
AB  - Fluorescence detection coupled to capillary electrophoresis (CE-FL) effectively
      separates molecules in solution and at the same time allows monitoring of the
      fluorescence spectrum of each individual species. The integration of separation
      and fluorescence detection results in a powerful method superior to the ensemble
      in-cuvette fluorescence measurement, in probing the binding interaction between
      ligands and quantum dots (QDs) in complex solutions. Forster resonance energy
      transfer (FRET) between fluorescent ligands and QDs could be readily detected by
      CE-FL, which together with the migration times of the fluorescent peaks provides
      an indication of the binding interaction between ligands and QDs. In the present
      study, the binding interaction between a multivalent ligand, polyhistidine
      peptide denderimer (PHPD), and CdSe-ZnS QDs was probed by CE-FL using the
      monovalent hexahistidine peptide as a control. Cy5 labeled PHPD assembles on
      glutathione capped QDs, showing a higher FRET signal than that of the assembly
      between Cy5 labeled hexahistidine peptide and QDs. Capillary electrophoresis
      further revealed that PHPD outcompetes other QD binding small molecules,
      peptides, and proteins in cell lysate. Our study demonstrates the power of CE-FL
      in analyzing the binding interaction between ligands and QDs in a complex binding
      solution. It also shows that clustering surface binding motifs yields multivalent
      ligands that can preferentially assemble with nanoparticles.

PMID- 21728333
TI  - Adulticidal activity of phthalides identified in Cnidium officinale rhizome to B-
      and Q-biotypes of Bemisia tabaci.
AB  - The residual contact toxicity of three benzofuranoids (Z)-butylidenephthalide
      (1), (3S)-butylphthalide (2), and (Z)-ligustilide (3) identified in the rhizome
      of Cnidium officinale (Apiaceae) to B- and Q-biotype females of Bemisia tabaci
      was evaluated using a leaf-dip bioassay. Results were compared with those of
      eight conventional insecticides. Based on 24 h LC(50) values, (Z)
      butylidenephthalide (254 ppm) and (Z)-ligustilide (268 ppm) were more toxic than
      (3S)-butylphthalide (339 ppm) against B-biotype females, whereas (Z)-ligustilide
      (254 ppm) and (3S)-butylphthalide (338 ppm) were more toxic than (Z)
      butylidenephthalide (586 ppm) against Q-biotype females. Thiamethoxam,
      imidacloprid, and acetamiprid differ significantly in toxicity between the B- and
      Q-biotype females (LC(50), 1.7 to 11.6 vs 364.5 to >3000 ppm). This original
      finding indicates that the phthalides and the neonicotinoids do not share a
      common mode of action or elicit cross-resistance. Structure-activity relationship
      indicates that the presence of conjugation rather than aromaticity appeared to
      play an important role for phthalide toxicities to the B-biotype females. Global
      efforts to reduce the level of highly toxic synthetic insecticides in the
      agricultural environment justify further studies on C. officinale rhizome-derived
      materials as potential insecticides for the control of B. tabaci populations.

PMID- 21728334
TI  - UV and IR spectroscopic studies of cold alkali metal ion-crown ether complexes in
      the gas phase.
AB  - We report UV photodissociation (UVPD) and IR-UV double-resonance spectra of
      dibenzo-18-crown-6 (DB18C6) complexes with alkali metal ions (Li(+), Na(+), K(+),
      Rb(+), and Cs(+)) in a cold, 22-pole ion trap. All the complexes show a number of
      vibronically resolved UV bands in the 36,000-38,000 cm(-1) region. The Li(+) and
      Na(+) complexes each exhibit two stable conformations in the cold ion trap (as
      verified by IR-UV double resonance), whereas the K(+), Rb(+), and Cs(+) complexes
      exist in a single conformation. We analyze the structure of the conformers with
      the aid of density functional theory (DFT) calculations. In the Li(+) and Na(+)
      complexes, DB18C6 distorts the ether ring to fit the cavity size to the small
      diameter of Li(+) and Na(+). In the complexes with K(+), Rb(+), and Cs(+), DB18C6
      adopts a boat-type (C(2v)) open conformation. The K(+) ion is captured in the
      cavity of the open conformer thanks to the optimum matching between the cavity
      size and the ion diameter. The Rb(+) and Cs(+) ions sit on top of the ether ring
      because they are too large to enter the cavity of the open conformer. According
      to time-dependent DFT calculations, complexes that are highly distorted to hold
      metal ions open the ether ring upon S(1)-S(0) excitation, and this is confirmed
      by extensive low-frequency progressions in the UVPD spectra.

PMID- 21728335
TI  - New anthranilic acid based antagonists with high affinity and selectivity for the
      human cholecystokinin receptor 1 (hCCK1-R).
AB  - The anthranilic acid diamides represent the most recent class of nonpeptide
      CCK(1) receptor (CCK(1)-R) antagonists. Herein we describe the second phase of
      the anthranilic acid C-terminal optimization using nonproteinogenic amino acids
      containing a phenyl ring in their side chain. The Homo-Phe derivative 2 (VL-0797)
      enhanced 12-fold the affinity for the rat CCK(1)-R affinity and 15-fold for the
      human CCK(1)-R relative to the reference compound 12 (VL-0395). The eutomer of 2
      (6) exhibited a nanomolar range affinity toward the human CCK(1)-R and was at
      least 400-fold selective for the CCK(1)-R over the CCK(2)-R. Molecular docking in
      the modeled CCK(1)-R and its validation by site-directed mutagenesis experiments
      showed that the 6 binding site overlaps that occupied by the C-terminal bioactive
      region of the natural agonist CCK. Owing to their interesting properties, new
      compounds provided by this study represent a solid basis for further advances
      aimed at synthesis of clinically valuable CCK(1)-R antagonists.

PMID- 21728336
TI  - Anti-Markovnikov hydroalkylation of allylic amine derivatives via a palladium
      catalyzed reductive cross-coupling reaction.
AB  - Palladium-catalyzed hydroalkylation of allylic amine derivatives by alkylzinc
      reagents is reported. This reductive cross-coupling reaction yields anti
      Markovnikov products using a variety of allylic amine protecting groups.
      Preliminary mechanistic studies suggest that a reversible beta-hydride
      elimination/hydride insertion process furnishes the primary Pd-alkyl
      intermediate, which then undergoes transmetalation followed by reductive
      elimination to form a new sp(3)-sp(3) carbon-carbon bond.

PMID- 21728337
TI  - Accurate predictions of nonpolar solvation free energies require explicit
      consideration of binding-site hydration.
AB  - Continuum solvation methods are frequently used to increase the efficiency of
      computational methods to estimate free energies. In this paper, we have evaluated
      how well such methods estimate the nonpolar solvation free-energy change when a
      ligand binds to a protein. Three different continuum methods at various levels of
      approximation were considered, viz., the polarized continuum model (PCM), a
      method based on cavity and dispersion terms (CD), and a method based on a linear
      relation to the solvent-accessible surface area (SASA). Formally rigorous double
      decoupling thermodynamic integration was used as a benchmark for the continuum
      methods. We have studied four protein-ligand complexes with binding sites of
      varying solvent exposure, namely the binding of phenol to ferritin, a biotin
      analogue to avidin, 2-aminobenzimidazole to trypsin, and a substituted
      galactoside to galectin-3. For ferritin and avidin, which have relatively hidden
      binding sites, rather accurate nonpolar solvation free energies could be obtained
      with the continuum methods if the binding site is prohibited to be filled by
      continuum water in the unbound state, even though the simulations and experiments
      show that the ligand replaces several water molecules upon binding. For the more
      solvent exposed binding sites of trypsin and galectin-3, no accurate continuum
      estimates could be obtained, even if the binding site was allowed or prohibited
      to be filled by continuum water. This shows that continuum methods fail to give
      accurate free energies on a wide range of systems with varying solvent exposure
      because they lack a microscopic picture of binding-site hydration as well as
      information about the entropy of water molecules that are in the binding site
      before the ligand binds. Consequently, binding affinity estimates based upon
      continuum solvation methods will give absolute binding energies that may differ
      by up to 200 kJ/mol depending on the method used. Moreover, even relative
      energies between ligands with the same scaffold may differ by up to 75 kJ/mol. We
      have tried to improve the continuum solvation methods by adding information about
      the solvent exposure of the binding site or the hydration of the binding site,
      and the results are promising at least for this small set of complexes.

PMID- 21728338
TI  - Multidrug resistance-associated protein 1 mediates 15-deoxy-Delta(12,14)
      prostaglandin J2-induced expression of glutamate cysteine ligase expression via
      Nrf2 signaling in human breast cancer cells.
AB  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a representative J
      series cyclopentenone prostaglandin bearing an electrophilic alpha,beta
      unsaturated carbonyl group. In the present study, treatment of human breast
      cancer MCF-7 cells with 15d-PGJ(2) caused the up-regulation of the glutamate
      cysteine ligase catalytic (GCLC) subunit, the rate-limiting enzyme in glutathione
      (GSH) synthesis. 15d-PGJ(2) treatment caused nuclear translocation and
      transactivation of Nrf2, a redox-sensitive transcription factor responsible for
      induced expression of antioxidant and other cytoprotective genes. siRNA knockdown
      of Nrf2 abrogated 15d-PGJ(2)-induced GCLC expression. Following 15d-PGJ(2)
      treatment, the intracellular GSH level was initially diminished but eventually
      enhanced even above the basal level. The reactive oxygen species (ROS) scavenger
      N-acetylcysteine (NAC) abolished the 15d-PGJ2-induced Nrf2 activation and GCLC
      expression. Pharmacologic inhibition or siRNA knockdown of Akt, the target of
      phosphoinositide 3-kinase (PI3-K), attenuated 15d-PGJ(2)-induced Nrf2 activation
      and GCLC expression, and NAC treatment inhibited phosphorylation of Akt, and
      subsequently Nrf2 activation and GCLC upregulation. 9,10-Dihydro-15-PGJ2, a
      nonelectrophilic analogue of 15d-PGJ(2) that lacks the ability to form a
      conjugate with GSH, failed to induce activation of Akt and Nrf2 as well as ROS
      generation. These findings, taken all together, suggest that intracellular
      accumulation of ROS formed as a consequence of initial depletion of GSH can
      activate Akt, which in turn induces Nrf2 activation and subsequently the
      expression of GCLC, leading to the restoration of GSH. Interestingly, the
      extracellular GSH level was increased, concomitantly with the depletion of the
      intracellular GSH following 15d-PGJ(2) treatment. However, 15d-PGJ(2) was unable
      to influence both intra- and extra-cellular GSH levels when multidrug resistance
      associated protein 1 (MRP1), the efflux pump for GSH conjugates, was blocked by
      its antagonist, MK571. Moreover, 15d-PGJ(2)-induced GCLC expression was
      attenuated by the MK571 and also by siRNA knockdown of MRP1, suggesting that MRP1
      contributes to 15d-PGJ(2)-mediated up-regulation of GCLC by pumping out the 15d
      PGJ(2)-GSH conjugate. It is speculated that 15d-PGJ(2), once effluxed through
      MRP, liberates from the GSH conjugate, and the free 15d-PGJ(2) re-enters the cell
      and forms the GSH conjugate again. In conclusion, MRP1 mediates Nrf2-dependent up
      regulation of GCLC in 15d-PGJ(2)-treated MCF-7 cells, possibly via a putative
      recycling loop of 15d-PGJ(2)-GSH conjugation.

PMID- 21728339
TI  - Strong inclusion of inorganic anions into beta-cyclodextrin immobilized to gold
      electrode.
AB  - The inclusion of inorganic anions such as SO(4)(2-), NO(3)(-), and HPO(4)(2-)
      into the cavity of beta-cyclodextrin monolayers on Au was examined by X-ray
      photoelectron spectroscopy (XPS), a quartz crystal microbalance (QCM), and
      chronocoulometric measurements of the competitive inclusion with ferrocene. The
      inclusion amounts of ferrocence in 0.2 M Na(2)SO(4), NaNO(3), and Na(2)HPO(4)
      solutions were less than 6% of the adsorption amount of beta-cyclodextrin on Au,
      resulting in the apparent inhibition of the ferrocene redox reaction. The surface
      association constants of these anions reached about 10 on a logarithmic scale and
      were much higher than those for the inclusion of common organic guest compounds.
      A stronger anion inclusion was also demonstrated by the QCM response
      corresponding to the replacement of a preincluded organic guest with sulfate upon
      the injection of the sulfate solution. Quantitative analysis of the XPS data
      suggested a 1:1 association for each of these anions per surface beta
      cyclodextrin. There was no detectable inclusion for ClO(4)(-), Cl(-), and Br(-).

PMID- 21728340
TI  - Changes in conformation at the cytoplasmic ends of the fifth and sixth
      transmembrane helices of a yeast G protein-coupled receptor in response to ligand
      binding.
AB  - The third intracellular loop (IL3) of G protein-coupled receptors (GPCRs) is an
      important contact domain between GPCRs and their G proteins. Previously, the IL3
      of Ste2p, a Saccharomyces cerevisiae GPCR, was suggested to undergo a
      conformational change upon activation as detected by differential protease
      susceptibility in the presence and absence of ligand. In this study using
      disulfide cross-linking experiments we show that the Ste2p cytoplasmic ends of
      helix 5 (TM5) and helix 6 (TM6) that flank the amino and carboxyl sides of IL3
      undergo conformational changes upon ligand binding, whereas the center of the IL3
      loop does not. Single Cys substitution of residues in the middle of IL3 led to
      receptors that formed high levels of cross-linked Ste2p, whereas Cys substitution
      at the interface of IL3 and the contiguous cytoplasmic ends of TM5 and TM6
      resulted in minimal disulfide-mediated cross-linked receptor. The alternating
      pattern of residues involved in cross-linking suggested the presence of a 3(10)
      helix in the middle of IL3. Agonist (WHWLQLKPGQPNleY) induced Ste2p activation
      reduced cross-linking mediated by Cys substitutions at the cytoplasmic ends of
      TM5 and TM6 but not by residues in the middle of IL3. Thus, the cytoplasmic ends
      of TM5 and TM6 undergo conformational change upon ligand binding. An alpha-factor
      antagonist (des-Trp, des-His-alpha-factor) did not influence disulfide-mediated
      Ste2p cross-linking, suggesting that the interaction of the N-terminus of alpha
      factor with Ste2p is critical for inducing conformational changes at TM5 and TM6.
      We propose that the changes in conformation revealed for residues at the ends of
      TM5 and TM6 are affected by the presence of G protein but not G protein
      activation. This study provides new information about role of specific residues
      of a GPCR in signal transduction and how peptide ligand binding activates the
      receptor.

PMID- 21728343
TI  - Use of olive biomass fly ash in the preparation of environmentally friendly
      mortars.
AB  - The incorporation of fly ash from olive biomass (FAOB) combustion in cogeneration
      plants into cement based mortars was explored by analyzing the chemical
      composition, mineralogical phases, particle size, morphology, and IR spectra of
      the resulting material. Pozzolanic activity was detected and found to be related
      with the presence of calcium aluminum silicates phases. The preparation of new
      olive biomass fly ash content mortars is effective by replacing either CaCO(3)
      filler or cement with FAOB. In fact, up to 10% of cement can be replaced without
      detracting from the mechanical properties of a mortar. This can provide an
      alternative way to manage the olive biomass fly ash as waste produced in thermal
      plants and reduce cement consumption in the building industry, and hence an
      economically and environmentally attractive choice.

PMID- 21728342
TI  - Palytoxin induces cell lysis by priming a two-step process in mcf-7 cells.
AB  - The cytolytic action of palytoxin (PlTX) was recognized long ago, but its
      features have remained largely undetermined. We used biochemical, morphological,
      physiological, and physical tools, to study the cytolytic response in MCF-7
      cells, as our model system. Cytolysis represented a stereotyped response induced
      by the addition of isotonic phosphate buffer (PBS) to cells that had been exposed
      to PlTX, after toxin removal and under optimal and suboptimal experimental
      conditions. Cytolysis was sensitive to osmolytes present during cell exposure to
      PlTX but not in the course of the lytic phase. Fluorescence microscopy showed
      that PlTX caused cell rounding and rearrangement of the actin cytoskeleton.
      Atomic force microscopy (AFM) was used to monitor PlTX effects in real time, and
      we found that morphological and mechanical properties of MCF-7 cells did not
      change during toxin exposure, but increased cell height and decreased stiffness
      at its surface were observed when PBS was added to PlTX-treated cells. The
      presence of an osmolyte during PlTX treatment prevented the detection of changes
      in morphological and mechanical properties caused by PBS addition to toxin
      treated cells, as detected by AFM. By patch-clamp technique, we confirmed that
      PlTX action involved the transformation of the Na(+),K(+)-ATPase into a channel
      and found that cell membrane capacitance was not changed by PlTX, indicating that
      the membrane surface area was not greatly affected in our model system. Overall,
      our findings show that the cytolytic response triggered by PlTX in MCF-7 cells
      includes a first phase, which is toxin-dependent and osmolyte-sensitive, priming
      cells to lytic events taking place in a separate phase, which does not require
      the presence of the toxin and is osmolyte-insensitive but is accompanied by
      marked reorganization of actin-based cytoskeleton and altered mechanical
      properties at the cell's surface. A model of the two-step process of PlTX-induced
      cytolysis is presented.

PMID- 21728341
TI  - A folate receptor-targeting nanoparticle minimizes drug resistance in a human
      cancer model.
AB  - Resistance to chemotherapy is a major obstacle in cancer therapy. The main
      purpose of this study is to evaluate the potential of a folate receptor-targeting
      nanoparticle to overcome/minimize drug resistance and to explore the underlying
      mechanisms. This is accomplished with enhanced cellular accumulation and
      retention of paclitaxel (one of the most effective anticancer drugs in use today
      and a well-known P-glycoprotein (P-gp) substrate) in a P-gp-overexpressing cancer
      model. The folate receptor-targeted nanoparticle, HFT-T, consists of a heparin
      folate-paclitaxel (HFT) backbone with an additional paclitaxel (T) loaded in its
      hydrophobic core. In vitro analyses demonstrated that the HFT-T nanoparticle was
      superior to free paclitaxel or nontargeted nanoparticle (HT-T) in inhibiting
      proliferation of P-gp-overexpressing cancer cells (KB-8-5), partially due to its
      enhanced uptake and prolonged intracellular retention. In a subcutaneous KB-8-5
      xenograft model, HFT-T administration enhanced the specific delivery of
      paclitaxel into tumor tissues and remarkably prolonged retention within tumor
      tissues. Importantly, HFT-T treatment markedly retarded tumor growth in a
      xenograft model of resistant human squamous cancer. Immunohistochemical analysis
      further indicated that increased in vivo efficacy of HFT-T nanoparticles was
      associated with a higher degree of microtubule stabilization, mitotic arrest,
      antiangiogenic activity, and inhibition of cell proliferation. These findings
      suggest that when the paclitaxel was delivered as an HFT-T nanoparticle, the drug
      is better retained within the P-gp-overexpressing cells than the free form of
      paclitaxel. These results indicated that the targeted HFT-T nanoparticle may be
      promising in minimizing P-gp related drug resistance and enhancing therapeutic
      efficacy compared with the free form of paclitaxel.

PMID- 21728344
TI  - Kinetic and chemical mechanism of malate synthase from Mycobacterium
      tuberculosis.
AB  - Malate synthase catalyzes the Claisen-like condensation of acetyl-coenzyme A
      (AcCoA) and glyoxylate in the glyoxylate shunt of the citric acid cycle. The
      Mycobacterium tuberculosis malate synthase G gene, glcB, was cloned, and the N
      terminal His(6)-tagged 80 kDa protein was expressed in soluble form and purified
      by metal affinity chromatography. A chromogenic 4,4'-dithiodipyridine assay did
      not yield linear kinetics, but the generation of an active site-directed mutant,
      C619S, gave an active enzyme and linear kinetics. The resulting mutant exhibited
      kinetics comparable to those of the wild type and was used for the full kinetic
      analysis. Initial velocity studies were intersecting, suggesting a sequential
      mechanism, which was confirmed by product and dead-end inhibition. The inhibition
      studies delineated the ordered binding of glyoxylate followed by AcCoA and the
      ordered release of CoA followed by malate. The pH dependencies of k(cat) and
      k(cat)/K(gly) are both bell-shaped, and catalysis depends on a general base (pK =
      5.3) and a general acid (pK = 9.2). Primary kinetic isotope effects determined
      using [C(2)H(3)-methyl]acetyl-CoA suggested that proton removal and carbon-carbon
      bond formation were partially rate-limiting. Solvent kinetic isotope effects on
      k(cat) suggested the hydrolysis of the malyl-CoA intermediate was also partially
      rate-limiting. Multiple kinetic isotope effects, utilizing D(2)O and [C(2)H(3)
      methyl]acetyl-CoA, confirmed a stepwise mechanism in which the step exhibiting
      primary kinetic isotope effects precedes the step exhibiting the solvent isotope
      effects. We combined the kinetic data and the pH dependence of the kinetic
      parameters with existing structural and mutagenesis data to propose a chemical
      mechanism for malate synthase from M. tuberculosis.

PMID- 21728345
TI  - Mechanism of inhibition of fatty acid amide hydrolase by sulfonamide-containing
      benzothiazoles: long residence time derived from increased kinetic barrier and
      not exclusively from thermodynamic potency.
AB  - Fatty acid amide hydrolase (FAAH) has emerged as a potential target for
      developing analgesic, anxiolytic, antidepressant, sleep-enhancing, and anti
      inflammatory drugs, and tremendous efforts have been made to discover potent and
      selective inhibitors of FAAH. Most known potent FAAH inhibitors described to date
      employ covalent mechanisms, inhibiting the enzyme either reversibly or
      irreversibly. Recently, a benzothiazole-based analogue (1) has been described
      possessing a high potency against FAAH yet lacking a structural feature
      previously known to interact with FAAH covalently. However, covalent inhibition
      of FAAH by 1 has not been fully ruled out, and the issue of reversibility has not
      been addressed. Confirming previous reports, 1 inhibited recombinant human FAAH
      (rhFAAH) with high potency with IC(50) ~2 nM. It displayed an apparently
      noncompetitive and irreversible inhibition, titrating rhFAAH stoichiometrically
      within normal assay times. The inhibition appeared to be time dependent, but the
      time dependence only improved potency by a small degree (from ~8 to ~2 nM).
      However, mass spectrometric analyses of the reaction mixture failed to reveal any
      cleavage product or covalent adduct and showed full recovery of the parent
      compound, ruling out covalent, irreversible inhibition. Dialysis revealed
      recovery of enzyme activity from enzyme-inhibitor complex over a prolonged time
      (>10 h), demonstrating that 1 is indeed a reversible, albeit slowly dissociating
      inhibitor of FAAH. Molecular docking indicated that the sulfonamide group of 1
      could form hydrogen bonds with several residues involved in catalysis, thereby
      mimicking the transition state. The long residence time displayed by 1 does not
      appear to derive exclusively from great thermodynamic potency and is consistent
      with an increased kinetic energy barrier that prevents dissociation from
      happening quickly.

PMID- 21728346
TI  - Coupled isotachophoretic preconcentration and electrophoretic separation using
      bidirectional isotachophoresis.
AB  - We present a novel technique for coupling isotachophoretic preconcentration and
      electrophoretic separation using bidirectional isotachophoresis (ITP).
      Bidirectional ITP simultaneously sets up sharp ITP interfaces between relatively
      high- and low-mobility cations and high- and low-mobility anions. These two
      interfaces can migrate toward each other and be described as ion concentration
      shock waves. We here demonstrate a bidirectional ITP process in which we use the
      interaction of these anionic and cationic ITP shock waves to trigger a
      transformation from ITP preconcentration to electrophoretic separation. We use
      anionic ITP to focus anionic sample species prior to shock interaction. The
      interaction of the counter-propagating anionic and cationic ITP shocks then
      changes the local pH (and ionic strength) of the focused analyte zones. Under
      this new condition, the analytes no longer focus and begin to separate
      electrophoretically. The method provides faster and much less dispersive
      transition from ITP preconcentration to electrophoretic separation compared with
      traditional (unidirectional) transient ITP. It eliminates the need for
      intermediate steps between focusing and separation, such as manual buffer
      exchanges. We illustrate the technique with numerical simulations of species
      transport equations. We have validated our simulations with experimental
      visualization of bidirectional ITP zones. We then show the effectiveness of the
      technique by coupling ITP preconcentration and high-resolution separation of a 1
      kbp DNA ladder via shock interaction in bidirectional ITP.

PMID- 21728347
TI  - Pure rotational spectrum and ring inversion tunnelling of silacyclobutane.
AB  - The ground state pure rotational spectrum of silacyclobutane (SCB) (c
      SiH(2)C(3)H(6)) has been investigated using both Fourier transform microwave
      (FTMW) and chirped pulse Fourier transform microwave (cp-FTMW) spectroscopies.
      Spectra of the (13)C, (29)Si, and (30)Si singly substituted isotopologues, in
      natural abundance, were recorded in the 6-24 GHz region along with those of the
      normal species. The ring inversion tunnelling splitting in the ground vibrational
      state was resolved and analyzed to determine the energy splitting of the two
      states: 75.7260(19) MHz. Structural analysis based on heavy atom substitution
      provided accurate geometric parameters including the bond lengths, bond angles,
      and ring puckering angle of the SCB ring backbone.

PMID- 21728348
TI  - Effect of fluorocarbon molecules confined between sliding self-mated PTFE
      surfaces.
AB  - We report on the frictional response and atomic process that occur when molecular
      fluorocarbon molecules of varying lengths are sheared between two
      polytetrafluoroethylene (PTFE) surfaces. The thicknesses of the molecular layers
      are also varied. The approach is classical molecular dynamics simulations using a
      reactive bond-order potential parametrized for fluorocarbons. The results
      indicate that the presence of the molecules has a significant impact on the
      measured friction and wear of the surfaces, and that this impact depends on the
      nature of the fluorocarbon molecules and the thickness of the molecular film. The
      molecular mechanisms responsible for these differences are presented.

PMID- 21728349
TI  - Negative thermal expansion coefficient of graphene measured by Raman
      spectroscopy.
AB  - The thermal expansion coefficient (TEC) of single-layer graphene is estimated
      with temperature-dependent Raman spectroscopy in the temperature range between
      200 and 400 K. It is found to be strongly dependent on temperature but remains
      negative in the whole temperature range with a room temperature value of (-8.0 +/
      0.7) * 10(-6) K(-1). The strain caused by the TEC mismatch between graphene and
      the substrate plays a crucial role in determining the physical properties of
      graphene, and hence its effect must be accounted for in the interpretation of
      experimental data taken at cryogenic or elevated temperatures.

PMID- 21728350
TI  - Dynamics on the electronically excited state surface of the bioluminescent
      firefly luciferase-oxyluciferin system.
AB  - Dynamics of the firefly luciferase-oxyluciferin complex in its electronic ground
      and excited states are studied using various theoretical approaches. By mimicking
      the physiological conditions with realistic models of the chromophore
      oxyluciferin, the enzyme luciferase, and solvating water molecules and by
      performing real time simulations with a molecular dynamics technique on the model
      surfaces, we reveal that the local chromophore-surrounding interaction patterns
      differ rather severely in the two states. Because of the presence of protein, the
      solvation dynamics of water around the chromophore is also peculiar and shows
      widely different time scales on the two terminal oxygen atoms. In addition,
      simulations of the emission with the quantum-mechanics/molecular-mechanics
      approach show a close relationship between the emission color variation and the
      environmental dynamics, mostly through electrostatic effects from the chromophore
      surrounding interaction. We also discuss the importance of considering the time
      scales of the luminescence and the dynamics of the interaction.

PMID- 21728351
TI  - Mesoporous coaxial titanium nitride-vanadium nitride fibers of core-shell
      structures for high-performance supercapacitors.
AB  - In this study, titanium nitride-vanadium nitride fibers of core-shell structures
      were prepared by the coaxial electrospinning, and subsequently annealed in the
      ammonia for supercapacitor applications. These core-shell (TiN-VN) fibers
      incorporated mesoporous structure into high electronic conducting transition
      nitride hybrids, which combined higher specific capacitance of VN and better rate
      capability of TiN. These hybrids exhibited higher specific capacitance (2 mV s(
      1), 247.5 F g(-1)) and better rate capability (50 mV s(-1), 160.8 F g(-1)), which
      promise a good candidate for high-performance supercapacitors. It was also
      revealed by electrochemical impedance spectroscopy (EIS) and X-ray photoelectron
      spectroscopy (XPS) characterization that the minor capacitance fade originated
      from the surface oxidation of VN and TiN.

PMID- 21728352
TI  - Aircraft emissions of methane and nitrous oxide during the alternative aviation
      fuel experiment.
AB  - Given the predicted growth of aviation and the recent developments of alternative
      aviation fuels, quantifying methane (CH(4)) and nitrous oxide (N(2)O) emission
      ratios for various aircraft engines and fuels can help constrain projected
      impacts of aviation on the Earth's radiative balance. Fuel-based emission indices
      for CH(4) and N(2)O were quantified from CFM56-2C1 engines aboard the NASA DC-8
      aircraft during the first Alternative Aviation Fuel Experiment (AAFEX-I) in 2009.
      The measurements of JP-8 fuel combustion products indicate that at low thrust
      engine states (idle and taxi, or 4% and 7% maximum rated thrusts, respectively)
      the engines emit both CH(4) and N(2)O at a mean +/- 1sigma rate of 170 +/- 160 mg
      CH(4) (kg Fuel)(-1) and 110 +/- 50 mg N(2)O (kg Fuel)(-1), respectively. At
      higher thrust levels corresponding to greater fuel flow and higher engine
      temperatures, CH(4) concentrations in engine exhaust were lower than ambient
      concentrations. Average emission indices for JP-8 fuel combusted at engine
      thrusts between 30% and 100% of maximum rating were -54 +/- 33 mg CH(4) (kg
      Fuel)(-1) and 32 +/- 18 mg N(2)O (kg Fuel)(-1), where the negative sign indicates
      consumption of atmospheric CH(4) in the engine. Emission factors for the
      synthetic Fischer-Tropsch fuels were statistically indistinguishable from those
      for JP-8.

PMID- 21728353
TI  - Chemical characterization and redox potential of coarse and fine particulate
      matter (PM) in underground and ground-level rail systems of the Los Angeles
      Metro.
AB  - A campaign was conducted to assess personal exposure of coarse (2.5 MUm < d(p) <
      10 MUm) and fine (d(p) < 2.5 MUm) PM for two lines of the L.A. Metro-a subway
      (red) and light-rail (gold) line. Concurrent measurements were taken at
      University of Southern California (USC) to represent ambient conditions. A
      comprehensive chemical analysis was performed including total and water-soluble
      metals, inorganic ions, elemental and organic carbon, and organic compounds. Mass
      balance showed that in coarse PM, iron makes up 27%, 6%, and 2% of gravimetric
      mass for the red line, the gold line, and USC, respectively; in fine PM, iron
      makes up 32%, 3%, and 1%. Ambient air is the primary source of inorganic ions and
      organic compounds for both lines. Noncrustal metals, particularly Cr, Mn, Co, Ni,
      Mo, Cd, and Eu, were elevated for the red line and, to a lesser degree, the gold
      line. Mo exhibited the greatest crustal enrichment factors. The enriched species
      were less water-soluble on the red line than corresponding species on the gold
      line. Bivariate analysis showed that reactive oxygen species (ROS) activity is
      strongly correlated with water-soluble Fe (R(2) = 0.77), Ni (R(2 )= 0.95), and OC
      (R(2 )= 0.92). A multiple linear regression model (R(2) = 0.94, p < 0.001) using
      water-soluble Fe and OC as predictor variables was developed to explain the
      variance in ROS. In addition, PM from the red line generates 65% and 55% more ROS
      activity per m(3) of air than PM from USC and the gold line, respectively;
      however, one unit of PM mass from the gold line may be as intrinsically toxic as
      one unit of PM from the red line.

PMID- 21728354
TI  - Applying the brakes to multisite SR protein phosphorylation: substrate-induced
      effects on the splicing kinase SRPK1.
AB  - To investigate how a protein kinase interacts with its protein substrate during
      extended, multisite phosphorylation, the kinetic mechanism of a protein kinase
      involved in mRNA splicing control was investigated using rapid quench flow
      techniques. The protein kinase SRPK1 phosphorylates ~10 serines in the arginine-
      serine-rich domain (RS domain) of the SR protein SRSF1 in a C- to N-terminal
      direction, a modification that directs this essential splicing factor from the
      cytoplasm to the nucleus. Transient-state kinetic experiments illustrate that the
      first phosphate is added rapidly onto the RS domain of SRSF1 (t(1/2) = 0.1 s)
      followed by slower, multisite phosphorylation at the remaining serines (t(1/2) =
      15 s). Mutagenesis experiments suggest that efficient phosphorylation rates are
      maintained by an extensive hydrogen bonding and electrostatic network between the
      RS domain of the SR protein and the active site and docking groove of the kinase.
      Catalytic trapping and viscosometric experiments demonstrate that while the
      phosphoryl transfer step is fast, ADP release limits multisite phosphorylation.
      By studying phosphate incorporation into selectively pre-phosphorylated forms of
      the enzyme-substrate complex, the kinetic mechanism for site-specific
      phosphorylation along the reaction coordinate was assessed. The binding affinity
      of the SR protein, the phosphoryl transfer rate, and ADP exchange rate were found
      to decline significantly as a function of progressive phosphorylation in the RS
      domain. These findings indicate that the protein substrate actively modulates
      initiation, extension, and termination events associated with prolonged,
      multisite phosphorylation.

PMID- 21728355
TI  - Photoreactivity of 5-fluorouracil under UVB light: photolysis and cytotoxicity
      studies.
AB  - The photodegradation of the chemotherapeutic agent 5-fluorouracil (5-FU) under
      UVB light was studied both in aqueous and methanol solutions and in systemic and
      topical formulations. As monitored by HPLC, photodegradation in solution takes
      place in a concentration dependent manner; thus, the solution for parenteral
      administration (10(-1) M) showed negligible loss of the active principle. On the
      contrary, the commercial cream containing 5% of 5-FU showed low stability under
      UVB exposure. When dissolved either in water or methanol, 5-FU yields two
      photoproducts which have been characterized as two isomers coming from the
      addition of the solvent to the 5,6 double bond of the drug. As a consequence,
      photomodified 5-FU loses its antiproliferative activity on HCT-15 and HeLa cells.
      MS analysis showed that photoaddition occurred with nucleophilic amino acids,
      such as cysteine and serine, while susceptible amino acids (cysteine and
      methionine) were oxidized. In fact, high production of the superoxide anion under
      UVB light as well as photooxidation of BSA suggests protein photodamage as a
      mechanism of photosensitization. Indeed, some phototoxicity was shown in
      experiments on NCTC keratinocytes and MCF-7 resistant cells irradiated with UVB
      light. The interactions with these biological targets may contribute to skin
      phototoxicity and photoallergy induced by 5-FU in vivo.

PMID- 21728356
TI  - Aqueous-solution-processed hybrid solar cells from poly(1,4-naphthalenevinylene)
      and CdTe nanocrystals.
AB  - Poly(1,4-naphthalenevinylene), prepared from a water-soluble precursor, was used
      to fabricate hybrid solar cells by blending with water-soluble CdTe nanocrystals
      (NCs) to act as the photoactive layer. In composites with CdTe NCs as the
      electron acceptors in a bulk heterojunction configuration, the devices exhibited
      a short-circuit current density of -6.14 mA/cm(2), an open-circuit voltage of
      0.44 V, a fill factor of 0.32, and a power conversion efficiency of 0.86% under
      AM1.5G conditions. Because the devices were fabricated from water-soluble
      materials, the procedure was generally simple and environmentally friendly in
      comparison to the conventional devices fabricated from oil-soluble materials.

PMID- 21728358
TI  - Structural and biochemical insights into the mechanism of fosfomycin
      phosphorylation by fosfomycin resistance kinase FomA.
AB  - We present here the crystal structures of fosfomycin resistance protein (FomA)
      complexed with MgATP, with ATP and fosfomycin, with MgADP and fosfomycin
      vanadate, with MgADP and the product of the enzymatic reaction, fosfomycin
      monophosphate, and with ADP at 1.87, 1.58, 1.85, 1.57, and 1.85 A resolution,
      respectively. Structures of these complexes that approximate different reaction
      steps allowed us to distinguish the catalytically active conformation of ATP and
      to reconstruct the model of the MgATP.fosfomycin complex. According to the model,
      the triphosphate tail of the nucleotide is aligned toward the phosphonate moiety
      of fosfomycin, in contest to the previously published MgAMPPNP complex, with the
      attacking fosfomycin oxygen positioned 4 A from the gamma-phosphorus of ATP. Site
      directed mutagenesis studies and comparison of these structures with that of
      homologous N-acetyl-l-glutamate and isopentenyl phosphate kinases allowed us to
      propose a model of phosphorylation of fosfomycin by FomA enzyme. A Mg cation
      ligates all three phosphate groups of ATP and together with positively charged
      K216, K9, K18, and H58 participates in the dissipation of negative charge during
      phosphoryl transfer, indicating that the transferred phosphate group is highly
      negatively charged, which would be expected for an associative mechanism. K216
      polarizes the gamma-phosphoryl group of ATP. K9, K18, and H58 participate in
      stabilization of the transition state. D150 and D208 play organizational roles in
      catalysis. S148, S149, and T210 participate in fosfomycin binding, with T210
      being crucial for catalysis. Hence, it appears that as in the homologous enzymes,
      FomA-catalyzed phosphoryl transfer takes place by an in-line predominantly
      associative mechanism.

PMID- 21728357
TI  - The flexible loop of Staphylococcus aureus IsdG is required for its degradation
      in the absence of heme.
AB  - Degradation of specific native proteins allows bacteria to rapidly adapt to
      changing environments when the activity of those proteins is no longer required.
      Although these processes are vital to bacterial survival, relatively little is
      known regarding how bacterial proteins are recognized and targeted for
      degradation. Staphylococcus aureus is an important human pathogen that requires
      iron for growth and pathogenesis. In the vertebrate host, S. aureus fulfills its
      iron requirement by obtaining heme iron from host hemoproteins via IsdG- and IsdI
      mediated heme degradation. IsdG and IsdI are structurally and mechanistically
      analogous but are differentially regulated by iron and heme availability.
      Specifically, IsdG is targeted for degradation in the absence of heme. Therefore,
      we utilized the differential regulation of IsdG and IsdI to investigate the
      mechanism of regulated proteolysis. In contrast to canonical protease recognition
      sequences, we show that IsdG is targeted for degradation by internally coded
      sequences. Specifically, a flexible loop near the heme-binding pocket is required
      for IsdG degradation in the absence of heme.

PMID- 21728359
TI  - A local entropic signature of specific ion hydration.
AB  - Monovalent ion hydration entropies are analyzed via energetic partitioning of the
      potential distribution theorem free energy. Extensive molecular dynamics
      simulations and free energy calculations are performed over a range of
      temperatures to determine the electrostatic and van der Waals components of the
      entropy. The far-field electrostatic contribution is negative and small in
      magnitude, and it does not vary significantly as a function of ion size,
      consistent with dielectric models. The local electrostatic contribution, however,
      varies widely as a function of ion size; the sign yields a direct indication of
      the kosmotropic (strongly hydrated) or chaotropic (weakly hydrated) nature of the
      ion hydration. The results provide a thermodynamic signature for specific ion
      effects in hydration and are consistent with experiments that suggest minimal
      perturbations of water structure outside the first hydration shell. The hydration
      entropies are also examined in relation to the corresponding entropies for the
      isoelectronic rare gas pairs; an inverse correlation is observed, as expected
      from thermodynamic hydration data.

PMID- 21728360
TI  - Support vector regression scoring of receptor-ligand complexes for rank-ordering
      and virtual screening of chemical libraries.
AB  - The community structure-activity resource (CSAR) data sets are used to develop
      and test a support vector machine-based scoring function in regression mode
      (SVR). Two scoring functions (SVR-KB and SVR-EP) are derived with the objective
      of reproducing the trend of the experimental binding affinities provided within
      the two CSAR data sets. The features used to train SVR-KB are knowledge-based
      pairwise potentials, while SVR-EP is based on physicochemical properties. SVR-KB
      and SVR-EP were compared to seven other widely used scoring functions, including
      Glide, X-score, GoldScore, ChemScore, Vina, Dock, and PMF. Results showed that
      SVR-KB trained with features obtained from three-dimensional complexes of the
      PDBbind data set outperformed all other scoring functions, including best
      performing X-score, by nearly 0.1 using three correlation coefficients, namely
      Pearson, Spearman, and Kendall. It was interesting that higher performance in
      rank ordering did not translate into greater enrichment in virtual screening
      assessed using the 40 targets of the Directory of Useful Decoys (DUD). To remedy
      this situation, a variant of SVR-KB (SVR-KBD) was developed by following a target
      specific tailoring strategy that we had previously employed to derive SVM-SP. SVR
      KBD showed a much higher enrichment, outperforming all other scoring functions
      tested, and was comparable in performance to our previously derived scoring
      function SVM-SP.

PMID- 21728361
TI  - Polymer/polymer blend solar cells with 2.0% efficiency developed by thermal
      purification of nanoscale-phase-separated morphology.
AB  - We have fabricated polymer/polymer blend solar cells consisting of poly(3
      hexylthiophene) as the electron donor and poly{2,7-(9,9-didodecylfluorene)-alt
      5,5-[4',7'-bis(2-thienyl)-2',1',3'-benzothiadiazole]} as the acceptor. The power
      conversion efficiency (PCE) was strongly dependent on solvents employed for spin
      coating. The best PCE of 2.0% was obtained for thermally annealed devices
      prepared from a chloroform solution, in contrast to devices fabricated from
      chlorobenzene and o-dichlorobenzene solutions. On the basis of the morphology
      performance relationship in the polymer blends examined by atomic force
      microscopy and the photoluminescence quenching measurements, we conclude that the
      highly efficient performance is achieved by thermal purification of nanoscale
      phase-separated domains formed by spin coating from chloroform.

PMID- 21728362
TI  - Free energies of the ion equilibrium partition of KCl into nanofiltration
      membranes based on transmembrane electrical potential and rejection.
AB  - The free energies of ion equilibrium partition between an aqueous KCl solution
      and nanofiltration (NF) membranes were investigated on the basis of the
      relationship of the transmembrane electrical potential (TMEP) and rejection. The
      measurements of TMEP and rejection were performed for Filmtec NF membranes in KCl
      solutions over a wide range of salt concentrations (1-60 mol.m(-3)) and pH values
      (3-10) at the feed side, with pressure differences in the range 0.1-0.6 MPa. The
      reflection coefficient and transport number, which were used to obtain the
      distribution coefficients on basis of irreversible thermodynamics, were fitted by
      the two-layer model with consideration of the activity coefficient. Evidence for
      dielectric exclusion under the experimental conditions was obtained by analyzing
      the rejection of KCl at the isoelectric point. The free energies were calculated,
      and the contribution of the electrostatic effect, dielectric exclusion, steric
      hindrance, and activity coefficient on the ion partitioning is elucidated. It is
      clearly demonstrated that the dielectric exclusion plays a central role.

PMID- 21728363
TI  - Facile fabrication of transparent superhydrophobic surfaces by spray deposition.
AB  - Herein, we present a one-step facile spray-deposition process for fabricating a
      new superhydrophobic surface with a novel statistical copolymer. The polymeric
      material is relatively inexpensive, easily prepared, transparent, solvent
      processable, very simple, and applicable to rugged substrates. The materials
      presented herein also feature a near-perfect superhydrophobic surface with a
      static water contact angle of 178 degrees  and a transmittance of higher than 75%
      at 550 nm wavelength.

PMID- 21728364
TI  - Quantification of 4-beta-hydroxycholesterol in human plasma using automated
      sample preparation and LC-ESI-MS/MS analysis.
AB  - It has recently been proposed that plasma levels of 4beta-hydroxycholesterol
      (4betaHC) may be indicative of cytochrome P450 3A4 (P450 3A) activity and
      therefore could be used to probe for P450 3A-mediated drug-drug interactions.
      With this in mind, we describe a highly sensitive and precise liquid
      chromatography-electrospray ionization-tandem mass spectrometry method for the
      measurement of 4betaHC in human plasma with a lower limit of quantification
      established at 2 ng/mL using 50 MUL of plasma. The entire sample preparation
      scheme including saponification and derivatization of 4betaHC to the
      corresponding dipicolinyl ester (DPE) was completed in less than 8 h using an
      automated sample preparation scheme enabling higher-throughput capabilities.
      Chromatographic resolution of 4betaHC from 4alpha-hydroxycholesterol and other
      endogenous isobaric species was achieved in 11-min using an isocratic gradient on
      a C18 column. Because of endogenous concentrations of 4betaHC in plasma, a stable
      isotope labeled (SIL) analogue, d7-4betaHC, was used as a surrogate analyte and
      measured in the standard curve and quality control samples prepared in plasma. A
      second SIL analogue, d4-4betaHC, was used as the internal standard. The intraday
      and interday accuracy for the assay was within 6% of nominal concentrations, and
      the precision for these measurements was less than 5% relative standard
      deviation. Rigorous stability assessments demonstrated adequate stability of
      endogenous 4betaHC in plasma and the corresponding DPE derivative for the
      analysis of clinical study samples. The results from clinical samples following
      treatment with a potent P450 3A inducer (rifampin) or inhibitor (ketoconazole)
      are reported and demonstrate the potential future application for this highly
      precise and robust analytical assay.

PMID- 21728365
TI  - Poly(vinyl alcohol) physical hydrogels: noncryogenic stabilization allows nano-
      and microscale materials design.
AB  - Physical hydrogels based on poly(vinyl alcohol), PVA, have an excellent safety
      profile and a successful history of biomedical applications. However, highly
      inhomogeneous and macroporous internal organization of these hydrogels as well as
      scant opportunities in bioconjugation with PVA have largely ruled out micro- and
      nanoscale control and precision in materials design and their use in
      (nano)biomedicine. To address these shortcomings, herein we report on the
      assembly of PVA physical hydrogels via "salting-out", a noncryogenic method. To
      facilitate sample visualization and analysis, we employ surface-adhered
      structured hydrogels created via microtransfer molding. The developed approach
      allows us to assemble physical hydrogels with dimensions across the length
      scales, from ~100 nm to hundreds of micrometers and centimeter sized structures.
      We determine the effect of the PVA molecular weight, concentration, and "salting
      out" times on the hydrogel properties, i.e., stability in PBS, swelling, and
      Young's modulus using exemplary microstructures. We further report on RAFT
      synthesized PVA and the functionalization of polymer terminal groups with RITC, a
      model fluorescent low molecular weight cargo. This conjugated PVA-RITC was then
      loaded into the PVA hydrogels and the cargo concentration was successfully varied
      across at least 3 orders of magnitude. The reported design of PVA physical
      hydrogels delivers methods of production of functionalized hydrogel materials
      toward diverse applications, specifically surface mediated drug delivery.

PMID- 21728366
TI  - Carotenoids and beta-cyclodextrin inclusion complexes: Raman spectroscopy and
      theoretical investigation.
AB  - In the present study, the inclusion processes of beta-carotene, astaxanthin,
      lycopene, and norbixin (NOR) into the beta-cyclodextrin (beta-CD) cavity were
      investigated by means of Raman spectroscopy and quantum mechanics calculations.
      The Raman nu(1) band assigned to C?C stretching was sensitive to the host-guest
      interaction and in general undergoes a blue shift (3-13 cm(-1)) after inclusion
      takes place, which is the consequence of the localization of single and double
      bonds. This is supported by the molecular modeling prediction, which inclusion
      complexes show the nu(1) band blue shifted by 1-8 cm(-1). The calculated
      complexation energies was small for most of derivatives and was found to be -11.1
      kcal mol(-1) for inclusion of AST and +0.27 kcal mol(-1) for NOR. The stability
      order was qualitatively correlated to topological parameters accounting for the
      opening angle of the chain. This means that after inclusion the guest molecules
      assume a slightly more extended conformation, which enhances the host-guest
      contact, improving the interaction energy. The results discussed here clearly
      demonstrate the matrix effect on the carotenes' spectroscopic profile and should
      contribute to fully characterize the raw samples.

PMID- 21728367
TI  - Two-dimensional chirped-pulse Fourier transform microwave spectroscopy.
AB  - Two-dimensional (2D) correlation techniques are developed for chirped-pulse
      Fourier transform microwave (CP-FTMW) spectroscopy. The broadband nature of the
      spectrometer coupled with fast digital electronics permits the generation of
      arbitrary pulse sequences and simultaneous detection of the 8-18 GHz region of
      the microwave spectrum. This significantly increases the number of rotation
      transitions that can be simultaneously probed, as well as the bandwidth in both
      frequency dimensions. We theoretically and experimentally evaluate coherence
      transfer of three- and four-level systems to relate the method with previous
      studies. We then extend the principles of single-quantum and autocorrelation to
      incorporate broadband excitation and detection. Global connectivity of the
      rotational energy level structure is demonstrated through the transfer of
      multiple coherences in a single 2D experiment. Additionally, open-system effects
      are observed from irradiating many-level systems. Quadrature detection in the
      indirectly measured frequency dimension and phase cycling are also adapted for 2D
      CP-FTMW spectroscopy.

PMID- 21728368
TI  - Stabilization of superparamagnetic iron oxide nanoclusters in concentrated brine
      with cross-linked polymer shells.
AB  - Iron oxide nanoparticles, in the form of sub-100-nm clusters, were synthesized in
      the presence of poly(acrylic acid) (PAA) or poly(styrene sulfonate-alt-maleic
      acid) (PSS-alt-MA) to provide electrosteric stabilization. The superparamagnetic
      nanoclusters were characterized using a superconducting quantum interference
      device (SQUID), transmission electron microscopy (TEM), dynamic light scattering
      (DLS), thermogravimetric analysis (TGA), and zeta potential measurements. To
      anchor the polymer shell on the nanoparticle surface, the polymer was cross
      linked for a range of cross-linking densities. For nanoclusters with only 12%
      (w/w) PSS-alt-MA, electrosteric stabilization was sufficient even in 8 wt % NaCl.
      For PAA, the cross-linked polymer shell was essentially permanent and did not
      desorb even upon dilution of the nanoparticles for iron oxide concentrations down
      to 0.014 wt %. Without cross-linking, over half of the polymer desorbed from the
      particle surfaces. This general approach of the adsorption of polymer stabilizers
      onto nanoparticles followed by cross-linking may be utilized for a wide variety
      of cross-linkable polymers without the need to form covalent bonds between the
      nanoparticles and polymer stabilizer. Thus, this cross-linking approach is an
      efficient and inexpensive method of stabilizing nanoparticles for large-scale
      applications, including the electromagnetic imaging of subsurface reservoirs,
      even at high salinity.

PMID- 21728369
TI  - Increasing the speed limit for hole transport in DNA.
AB  - Transport of positive charge or holes in DNA occurs via a thermally activated
      multi-step hopping mechanism. The fastest hopping rates reported to date are
      those for repeating poly(purine) sequences in which hopping occurs via a random
      walk mechanism with rate constants of k(hop) = 4.3 * 10(9) s(-1) for poly(dG) and
      1.2 * 10(9) s(-1) for poly(dA). We report here the dynamics of charge separation
      in DNA conjugates possessing repeating 7-deazaadenine (dzA) sequences. These data
      provide an estimated value of k(hop) = 4.2 * 10(10) s(-1) for poly(dzA), an order
      of magnitude faster than for poly(dG).

PMID- 21728370
TI  - An exceptional 54-fold interpenetrated coordination polymer with 10(3)-srs
      network topology.
AB  - Entanglement is one of the most important features of coordination polymer
      frameworks and has attracted considerable attention due to its aesthetic and
      topological interest. Among entangled systems, interpenetrating frameworks
      represent an intriguing subset; however, there are few examples of materials
      containing very high levels of interpenetration. In this work a coordination
      polymer with 10(3)-srs topology, constructed from a star-like tridentate ligand,
      tri(4-imidazolylphenyl)amine, and Ag(I) ions, has been hydrothermally
      synthesized. It contains a record 54 interpenetrating networks.

PMID- 21728371
TI  - A biomimetic approach to enhancing interfacial interactions: polydopamine-coated
      clay as reinforcement for epoxy resin.
AB  - A facile biomimetic method was developed to enhance the interfacial interaction
      in polymer-layered silicate nanocomposites. By mimicking mussel adhesive
      proteins, a monolayer of polydopamine was constructed on clay surface by a
      controllable coating method. The modified clay (D-clay) was incorporated into an
      epoxy resin, it is found that the strong interfacial interactions brought by the
      polydopamine benefits not only the dispersion of the D-clay in the epoxy but also
      the effective interfacial stress transfer, leading to greatly improved
      thermomechanical properties at very low inorganic loadings. Rheological and
      infrared spectroscopic studies show that the interfacial interactions between the
      D-clay and epoxy are dominated by the hydrogen bonds between the catechol
      enriched polydopamine and the epoxy.

PMID- 21728372
TI  - Adhesion promotion via noncovalent interactions in self-healing polymers.
AB  - Dimethylnorbornene ester (DNE) is successfully used as a noncovalent adhesion
      promoter. DNE was confirmed to copolymerize with dicyclopentadiene (DCPD) to
      yield a copolymer with better adhesion to an EPON 828 epoxy matrix relative to
      poly(DCPD) alone. The mechanical properties of the copolymer were comparable to
      that of poly(DCPD) alone. An optimized blend of the monomers was encapsulated
      using a urea-formaldheyde microencapsulation procedure and the resulting capsules
      were used for in situ self-healing experiments. Improved healing efficiency was
      observed for samples containing the DCPD/DNE capsules under conditions in which
      the monomers were efficiently polymerized.

PMID- 21728373
TI  - NaBH4-induced assembly of immobilized Au nanoparticles into chainlike structures
      on a chemically modified glass surface.
AB  - A facile method of obtaining chainlike assemblies of gold nanoparticles (AuNPs)
      on a chemically modified glass surface based on NaBH(4) treatment is developed.
      Citrate-stabilized AuNPs (17 nm) are immobilized on a glutaraldehyde
      functionalized glass surface and assembled into chainlike structures after
      treatment with aqueous sodium borohydride (NaBH(4)) solution. The production and
      morphology of the AuNP chainlike assemblies are controlled by the density of the
      immobilized NPs, the concentration of NaBH(4) solution, and the treatment time.
      The AuNP assemblies are stable in water and can undergo drying. X-ray
      photoelectron spectroscopic data show that the number of citrate ions on the
      AuNPs decreased by 43% after treatment with 5 mg/mL NaBH(4) solution. The NaBH(4)
      induced partial removal of the citrate ions and the roughness of the glass
      surface greatly affect the binding force of AuNPs on the substrate. The
      immobilized AuNPs begin to move at the solid-liquid interface without desorbing
      when the strength of the binding force was decreased. These mobile NPs form
      chainlike assemblies under the driving force of van der Waals interaction and
      diffusion. This interface-based formation of chainlike assemblies of AuNPs may
      provide a simple protocol for the 1D assembly of other Au-coated colloidal
      nanoparticles.

PMID- 21728374
TI  - Facile synthesis of thick films of poly(methyl methacrylate), poly(styrene), and
      poly(vinyl pyridine) from Au surfaces.
AB  - Atom transfer radical polymerization (ATRP) is commonly used to grow polymer
      brushes from Au surfaces, but the resulting film thicknesses are usually
      significantly less than with ATRP from SiO(2) substrates. On Au, growth of
      poly(methyl methacrylate) (PMMA) blocks from poly(tert-butyl acrylate) brushes
      occurs more rapidly than growth of PMMA from initiator monolayers, suggesting
      that the disparity between growth rates from Au and SiO(2) stems from the Au
      surface. Radical quenching by electron transfer from Au is probably not the
      termination mechanism because polymerization from thin, cross-linked initiators
      gives film thicknesses that are essentially the same as the thicknesses of films
      grown from SiO(2) under the same polymerization conditions. However, this result
      is consistent with termination through desorption of thiols from noncross-linked
      films, and reaction of these thiols with growing polymer chains. The enhanced
      stability of cross-linked initiators allows ATRP at temperatures up to ~100 
      degrees C and enables the growth of thick films of PMMA (350 nm), polystyrene
      (120 nm) and poly(vinyl pyridine) (200 nm) from Au surfaces in 1 h. At
      temperatures >100  degrees C, the polymer brush layers delaminate as large area
      films.

PMID- 21728375
TI  - Three-dimensional type II ZnO/ZnSe heterostructures and their visible light
      photocatalytic activities.
AB  - We report a method for synthesizing three distinct type II 3D ZnO/ZnSe
      heterostructures through simple solution-based surface modification reactions in
      which polycrystalline ZnSe nanoparticles formed on the surfaces of single
      crystalline ZnO building blocks of 3D superstructures. The experimental results
      suggested a possible formation mechanism for these heterostructures. The
      formation of the ZnO/ZnSe heterostructures was assumed to result from a
      dissolution-recrystallization mechanism. The optical properties of the 3D
      ZnO/ZnSe heterostructures were probed by UV-vis diffuse reflectance spectroscopy.
      The 3D ZnO/ZnSe heterostructures exhibited absorption in the visible spectral
      region. The visible photocatalytic activities of 3D ZnO/ZnSe heterostructures
      were much higher than those of the 3D pure ZnO structures. The activities of the
      3D ZnO/ZnSe heterostructures varied according to the structures under visible
      light. The morphologies and exposed crystal faces of pure ZnO building blocks
      prior to surface modification had a significant effect on the visible light
      photocatalytic processes of ZnO/ZnSe heterostructures after surface modification.

PMID- 21728376
TI  - Control of superhydrophilicity/superhydrophobicity using silicon nanowires via
      electroless etching method and fluorine carbon coatings.
AB  - Surface roughness is promotive of increasing their hydrophilicity or
      hydrophobicity to the extreme according to the intrinsic wettability determined
      by the surface free energy characteristics of a base substrate. Top-down etched
      silicon nanowires are used to create superhydrophilic surfaces based on the
      hemiwicking phenomenon. Using fluorine carbon coatings, surfaces are converted
      from superhydrophilic to superhydrophobic to maintain the Cassie-Baxter state
      stability by reducing the surface free energy to a quarter compared with
      intrinsic silicon. We present the robust criteria by controlling the height of
      the nanoscale structures as a design parameter and design guidelines for
      superhydrophilic and superhydrophobic conditions. The morphology of the silicon
      nanowires is used to demonstrate their critical height exceeds several hundred
      nanometers for superhydrophilicity, and surpasses a micrometer for
      superhydrophobicity. Especially, SiNWs fabricated with a height of more than a
      micrometer provide an effective means of maintaining superhydrophilic (<10
      degrees ) long-term stability.

PMID- 21728377
TI  - Smart nanotoxicity testing for biodiversity conservation.

PMID- 21728378
TI  - Binding of alpha,alpha-disubstituted amino acids to arginase suggests new avenues
      for inhibitor design.
AB  - Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to
      form L-ornithine and urea, and aberrant arginase activity is implicated in
      various diseases such as erectile dysfunction, asthma, atherosclerosis, and
      cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful.
      Continuing our efforts to expand the chemical space of arginase inhibitor design
      and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase
      I, we now report the first study of the binding of alpha,alpha-disubstituted
      amino acids to arginase. Specifically, we report the design, synthesis, and assay
      of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2
      (difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and
      Plasmodium falciparum arginase complexed with these inhibitors reveal the
      exclusive binding of the L-stereoisomer; the additional alpha-substituent of each
      inhibitor is readily accommodated and makes new intermolecular interactions in
      the outer active site of each enzyme. Therefore, this work highlights a new
      region of the protein surface that can be targeted for additional affinity
      interactions, as well as the first comparative structural insights on inhibitor
      discrimination between a human and a parasitic arginase.

PMID- 21728379
TI  - The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest
      acetylation coordinates organ-specific fuel switching.
AB  - The elucidation of extra-nuclear lysine acetylation has been of growing interest,
      as the cosubstrate for acetylation, acetyl CoA, is at a key metabolic
      intersection. Our hypothesis was that mitochondrial and cytoplasmic protein
      acetylation may be part of a fasted/re-fed feedback control system for the
      regulation of the metabolic network in fuel switching, where acetyl CoA would be
      provided by fatty acid oxidation, or glycolysis, respectively. To test this, we
      characterized the mitochondrial and cytoplasmic acetylome in various organs that
      have a high metabolic rate relative to their mass, and/or switch fuels, under
      fasted and re-fed conditions (brain, kidney, liver, skeletal muscle, heart
      muscle, white and brown adipose tissues). Using immunoprecipitation, coupled with
      LC-MS/MS label free quantification, we show there is a dramatic variation in
      global quantitative profiles of acetylated proteins from different organs. In
      total, 733 acetylated peptides from 337 proteins were identified and quantified,
      out of which 31 acetylated peptides from the metabolic proteins that may play
      organ-specific roles were analyzed in detail. Results suggest that fasted/re-fed
      acetylation changes coordinated by organ-specific (de)acetylases in insulin
      sensitive versus -insensitive organs may underlie fuel use and switching.
      Characterization of the tissue-specific acetylome should increase understanding
      of metabolic conditions wherein normal fuel switching is disrupted, such as in
      Type II diabetes.

PMID- 21728380
TI  - Stereoselective construction of quaternary carbon stereocenters via a semipinacol
      rearrangement strategy.
AB  - Quaternary carbon stereocenters are found in a broad range of organic compounds,
      including important bioactive natural products and medicinal agents. Given their
      ubiquity and the significant synthetic challenges they present, quaternary carbon
      stereocenters have long attracted great interest from synthetic organic chemists.
      Numerous efforts have been devoted to their construction, leading to a spectrum
      of strategies for creating stereogenic quaternary carbon centers. In this
      context, the semipinacol rearrangement has proven successful. In this extension
      of the pinacol rearrangement, the 1,2-carbon-to-carbon migration in a 1,2-diol
      has been expanded to include leaving groups other than the hydroxyl group.  Over
      the past decade, our laboratory has explored the semipinacol rearrangement
      strategy for the stereoselective construction of quaternary carbon stereocenters.
      We have investigated various substrates, including 2,3-epoxy alcohols (also
      termed alpha-hydroxy epoxides), 2,3-aziridino alcohols, and allylic alcohols.
      Several promoters that effect the semipinacol rearrangement have been identified,
      including Lewis acids based on Al, Sm, B, Zn, and Ti for the rearrangement of
      alpha-hydroxy epoxides and 2,3-aziridino alcohols; cationic halogen species for
      the rearrangement of allylic alcohols; and cinchona alkaloids and chiral
      phosphoric acid for the asymmetric semipinacol rearrangement. Our research
      efforts have led to a series of valuable synthetic methods, including (1) a
      tandem semipinacol rearrangement and Meerwein-Ponndorf-Verley reduction, (2) a
      tandem semipinacol rearrangement and Tishchenko reaction, (3) a tandem
      semipinacol rearrangement with either an allylation or a propargylation, (4) a
      tandem semipinacol rearrangement and Schmidt reaction, (5) a semipinacol
      rearrangement of 2,3-aziridino alcohols, (6) a semipinacol rearrangement of
      allylic alcohols induced by halogen cation, (7) a tandem aziridination and
      semipinacol rearrangement of allylic alcohols, and (8) asymmetric semipinacol
      rearrangements with chiral organic catalysts. One hallmark of these reactions is
      the creation of stereogenic quaternary carbon centers with high levels of
      stereocontrol. In this Account, we describe the development of these
      synthetically useful methodologies and their successful application to the total
      syntheses of natural products.  Our results demonstrate that the semipinacol
      rearrangement of carefully designed substrates constitutes an efficient approach
      to the stereoselective construction of quaternary carbon centers. These reactions
      have produced a broad array of useful compounds that lend themselves to further
      elaboration. Furthermore, the total synthesis of a series of alkaloids, with
      significant bioactivity and intriguing molecular architecture, was achieved
      through these semipinacol rearrangement strategies, highlighting their synthetic
      value.

PMID- 21728381
TI  - Preparation of a 12-membered open-cage fullerendione through silane/borane
      promoted formation of ketal moieties and oxidation of a vicinal fullerendiol.
AB  - [60]Fullerene mixed peroxide C(60) (OH)(Cl)(OOtBu) reacts with
      PhMe(2)SiH/B(C(6)F(5))(3) to give oxahomofullerene. Mechanistic investigation
      indicates that the hydroxyl group in the central pentagon ring is essential to
      convert the tert-butylperoxo group into a ketal moiety. Migration of the silyl
      group and transformation of the siloxy group into a phenyl group are observed in
      the deprotection of the fullerene bound siloxy group. A 12-membered open-cage
      fullerendione was obtained through oxidation of a [6,6]-fullerendiol. This
      orifice could be closed to form ketal/hemiketal moieties by BF(3)-catalyzed
      reaction with methanol. All of the new fullerene derivatives were characterized
      by spectroscopic data, and structure of the open-cage fullerendione was also
      confirmed by single-crystal X-ray analysis.

PMID- 21728382
TI  - Second-order Moller-Plesset calculations of total ground-state energies of
      tetrahedral and octahedral molecules at equilibrium, confronted with some model
      dependent scaling properties.
AB  - Using second-order Moller-Plesset (MP2) optimized geometries, calculations of
      total energies of some 20 tetrahedral and octahedral molecules have been carried
      out. We have then confronted these first-principles results, which of course
      include a fraction of the electronic correlation energy, with some model
      dependent scaling properties. In particular, one scaling relation emerging from
      the semiclassical Thomas-Fermi electron density method relates the known nuclear
      nuclear potential energy, V(nn), at equilibrium to the electron-nuclear term,
      V(en), and the total kinetic energy.

PMID- 21728383
TI  - Studying the role of common membrane surface functionalities on adsorption and
      cleaning of organic foulants using QCM-D.
AB  - Adsorption of organic foulants on nanofiltration (NF) and reverse osmosis (RO)
      membrane surfaces strongly affects subsequent fouling behavior by modifying the
      membrane surface. In this study, impact on organic foulant adsorption of specific
      chemistries including those in commercial thin-film composite membranes was
      investigated using self-assembled monolayers with seven different ending chemical
      functionalities (-CH(3), -O-phenyl, -NH(2), ethylene-glycol, -COOH, -CONH(2), and
      -OH). Adsorption and cleaning of protein (bovine serum albumin) and
      polysaccharide (sodium alginate) model foulants in two solution conditions were
      measured using quartz crystal microbalance with dissipation monitoring, and were
      found to strongly depend on surface functionality. Alginate adsorption correlated
      with surface hydrophobicity as measured by water contact angle in air; however,
      adsorption of BSA on hydrophilic -COOH, -NH(2), and -CONH(2) surfaces was high
      and dominated by hydrogen bond formation and electrostatic attraction. Adsorption
      of both BSA and alginate was the fastest on -COOH, and adsorption on -NH(2) and 
      CONH(2) was difficult to remove by surfactant cleaning. BSA adsorption kinetics
      was shown to be markedly faster than that of alginate, suggesting its importance
      in the formation of the conditioning layer. Surface modification to render -OH or
      ethylene-glycol functionalities are expected to reduce membrane fouling.

PMID- 21728384
TI  - Reversible tunability of the near-infrared valence band plasmon resonance in Cu(2
      x)Se nanocrystals.
AB  - We demonstrate that colloidal Cu(2-x)Se nanocrystals exhibit a well-defined
      infrared absorption band due to the excitation of positive charge carrier
      oscillations (i.e., a valence band plasmon mode), which can be tuned reversibly
      in width and position by varying the copper stoichiometry. The value of x could
      be incrementally varied from 0 (no plasmon absorption, then a broad peak at 1700
      nm) to 0.4 (narrow plasmon band at 1100 nm) by oxidizing Cu(2)Se nanocrystals
      (upon exposure either to oxygen or to a Ce(IV) complex), and it could be
      incrementally restored back to zero by the addition of a Cu(I) complex. The
      experimentally observed plasmonic behavior is in good agreement with calculations
      based on the electrostatic approximation.

PMID- 21728385
TI  - G protein-coupled receptor kinase 5 phosphorylation of hip regulates
      internalization of the chemokine receptor CXCR4.
AB  - Regulation of the magnitude, duration, and localization of G protein-coupled
      receptor (GPCR) signaling responses is controlled by desensitization,
      internalization, and downregulation of the activated receptor. Desensitization is
      initiated by the phosphorylation of the activated receptor by GPCR kinases (GRKs)
      and the binding of the adaptor protein arrestin. In addition to phosphorylating
      activated GPCRs, GRKs have been shown to phosphorylate a variety of additional
      substrates. An in vitro screen for novel GRK substrates revealed Hsp70
      interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and
      stoichiometrically phosphorylated Hip in vitro. The primary binding domain of
      GRK5 was mapped to residues 303-319 on Hip, while the major site of
      phosphorylation was identified to be Ser-346. GRK5 also bound to and
      phosphorylated Hip on Ser-346 in cells. While Hip was previously implicated in
      chemokine receptor trafficking, we found that the phosphorylation of Ser-346 was
      required for proper agonist-induced internalization of the chemokine receptor
      CXCR4. Taken together, Hip has been identified as a novel substrate of GRK5 in
      vitro and in cells, and phosphorylation of Hip by GRK5 plays a role in modulating
      CXCR4 internalization.

PMID- 21728386
TI  - Ultra-fast digital tomosynthesis reconstruction using general-purpose GPU
      programming for image-guided radiation therapy.
AB  - The purpose of this work is to demonstrate an ultra-fast reconstruction technique
      for digital tomosynthesis (DTS) imaging based on the algorithm proposed by
      Feldkamp, Davis, and Kress (FDK) using standard general-purpose graphics
      processing unit (GPGPU) programming interface. To this end, the FDK-based DTS
      algorithm was programmed "in-house" with C language with utilization of 1) GPU
      and 2) central processing unit (CPU) cards. The GPU card consisted of 480
      processing cores (2 x 240 dual chip) with 1,242 MHz processing clock speed and
      1,792 MB memory space. In terms of CPU hardware, we used 2.68 GHz clock speed,
      12.0 GB DDR3 RAM, on a 64-bit OS. The performance of proposed algorithm was
      tested on twenty-five patient cases (5 lung, 5 liver, 10 prostate, and 5 head-and
      neck) scanned either with a full-fan or half-fan mode on our cone-beam computed
      tomography (CBCT) system. For the full-fan scans, the projections from 157.5
      degrees -202.5 degrees  (45 degrees -scan) were used to reconstruct coronal DTS
      slices, whereas for the half-fan scans, the projections from both 157.5 degrees 
      202.5 degrees  and 337.5 degrees -22.5 degrees  (2 x 45 degrees -scan) were used
      to reconstruct larger FOV coronal DTS slices. For this study, we chose 45 degrees
      -scan angle that contained ~80 projections for the full-fan and ~160 projections
      with 2 x 45 degrees -scan angle for the half-fan mode, each with 1024 x 768
      pixels with 32-bit precision. Absolute pixel value differences, profiles, and
      contrast-to-noise ratio (CNR) calculations were performed to compare and evaluate
      the images reconstructed using GPU- and CPU-based implementations. The time
      dependence on the reconstruction volume was also tested with (512 x 512) x 16,
      32, 64, 128, and 256 slices. In the end, the GPU-based implementation achieved,
      at most, 1.3 and 2.5 seconds to complete full reconstruction of 512 x 512 x 256
      volume, for the full-fan and half-fan modes, respectively. In turn, this meant
      that our implementation can process > 13 projections-per-second (pps) and > 18
      pps for the full-fan and half-fan modes, respectively. Since commercial CBCT
      system nominally acquires 11 pps (with 1 gantry-revolution-per-minute), our GPU
      based implementation is sufficient to handle the incoming projections data as
      they are acquired and reconstruct the entire volume immediately after completing
      the scan. In addition, on increasing the number of slices (hence volume) to be
      reconstructed from 16 to 256, only minimal increases in reconstruction time were
      observed for the GPU-based implementation where from 0.73 to 1.27 seconds and
      1.42 to 2.47 seconds increase were observed for the full-fan and half-fan modes,
      respectively. This resulted in speed improvement of up to 87 times compared with
      the CPU-based implementation (for 256 slices case), with visually identical
      images and small pixel-value discrepancies (< 6.3%), and CNR differences (<
      2.3%). With this achievement, we have shown that time allocation for DTS image
      reconstruction is virtually eliminated and that clinical implementation of this
      approach has become quite appealing. In addition, with the speed achievement,
      further image processing and real-time applications that was prohibited prior due
      to time restrictions can now be tempered with.

PMID- 21728387
TI  - Feasibility of non-coplanar tomotherapy for lung cancer stereotactic body
      radiation therapy.
AB  - To quantify the dosimetric gains from non-coplanar helical tomotherapy (HT) arcs
      for stereotactic body radiation therapy (SBRT) of lung cancer, we created oblique
      helical arcs by rotating patient's CT images. Ten, 20 and 30 degrees of yaws were
      introduced in the treatment planning for a patient with a hypothetical lung tumor
      at the upper, middle and lower portion of the right lung, and the upper and
      middle left lung. The planning target volume (PTV) was 43 cm(3). 60 Gy was
      prescribed to the PTV. Dose to organs at risk (OARs), which included the lungs,
      heart, spinal cord and chest wall, was optimized using a 2.5 cm jaw, 0.287 pitch
      and modulation factor of 2.5. Composite plans were generated by dose summation of
      the resultant plans. These plans were evaluated for its conformity index (R(x))
      and percentile volume of lung receiving radiation dose of x Gy (V(x)). Conformity
      index was defined by the ratio of x percent isodose volume and PTV. The results
      show that combination of non-coplanar arcs reduced R(50) by 4.5%, R(20) by 26%
      and R(10) by 30% on average. Non-coplanar arcs did not affect V(20) but reduced
      V(10) and V(5) by 10% and 24% respectively. Composite of the non-coplanar arcs
      also reduced maximum dose to the spinal cord by 20-39%. Volume of chest wall
      receiving higher than 30 Gy was reduced by 48% on average. Heart dose reduction
      was dependent on the location of the PTV and the choice of non-coplanar
      orientations. Therefore we conclude that non-coplanar HT arcs significantly
      improve critical organ sparing in lung SBRT without changing the PTV dose
      coverage.

PMID- 21728388
TI  - Protons safely allow coverage of high-risk nodes for patients with regionally
      advanced non-small-cell lung cancer.
AB  - Our objective was to determine if protons allow for the expansion of treatment
      volumes to cover high-risk nodes in patients with regionally advanced non-small
      cell lung cancer. In this study, 5 consecutive patients underwent external-beam
      radiotherapy treatment planning. Four treatment plans were generated for each
      patient: 1) photons (x-rays) to treat positron emission tomography (PET)-positive
      gross disease only to 74 Gy (XG); 2) photons (x-rays) to treat high-risk nodes to
      44 Gy and PET-positive gross disease to 74 Gy (XNG); 3) protons to treat PET
      positive gross disease only to 74 cobalt gray equivalent (PG); and 4) protons to
      treat high-risk nodes to 44 CGE and PET-positive gross disease to 74 CGE (PNG).
      We defined high-risk nodes as mediastinal, hilar, and supraclavicular lymph nodal
      stations anatomically adjacent to the foci of PET-positive gross disease. Four
      dimensional computed tomography was utilized for all patients to account for
      tumor motion. Standard normal-tissue constraints were utilized. Our results
      showed that proton plans for all patients were isoeffective with the
      corresponding photon (x-ray) plans in that they achieved the desired target doses
      while respecting normal-tissue constraints. In spite of the larger volumes
      covered, median volume of normal lung receiving 10 CGE or greater (V10Gy/CGE),
      median V20Gy/CGE, and mean lung dose were lower in the proton plans (PNG)
      targeting gross disease and nodes when compared with the photon (x-ray) plans
      (XG) treating gross disease alone. In conclusion, proton plans demonstrated the
      potential to safely include high-risk nodes without increasing the volume of
      normal lung irradiated when compared to photon (x-ray) plans, which only targeted
      gross disease.

PMID- 21728389
TI  - Assessment of pulmonary fibrosis after radiotherapy (RT) in breast conserving
      surgery: comparison between conventional external beam RT (EBRT) and
      intraoperative RT with electrons (ELIOT).
AB  - The aim of this study was to assess the frequency and the grade of RT-induced
      pulmonary fibrosis in patients who underwent EBRT compared to patients who
      underwent ELIOT. One-hundred-seventy-eight patients enrolled in a prospective
      randomized phase III trial to compare the efficacy of ELIOT (a single dose of 21
      Gy prescribed at the 90% isodose) versus EBRT (50 Gy to the whole breast plus a
      10 Gy boost to the tumour bed), underwent a spiral 16-detector row Computed
      Tomography (CT) examination to assess RT-induced pulmonary fibrosis: 83 patients
      in the EBRT arm and 95 in the ELIOT arm. All patients (age range 48-75 years)
      were affected by unicentric infiltrating carcinoma of the breast with diameter <
      2.5 cm. This study was approved by our Institutional Ethical Committee and
      informed consent was obtained from each patient. Two observers, blinded to
      patient's randomization, independently evaluated each CT examination and assigned
      a fibrosis score (Grades 0 to 3). Inter-observer agreement for the fibrosis score
      was evaluated and a consensus between observers was obtained. Differences in
      fibrosis score between the two arms were evaluated by Chi Square test and Odds
      Ratio (OR) with 95% Confidence Intervals (CI). Pulmonary fibrosis was diagnosed
      in 42 patients (23.6%): 38 (90%) were in the EBRT arm and 4 (10%) in the ELIOT
      arm (p < 0.0001); twenty-six of them were Grade 1 (one ELIOT), fifteen were Grade
      2 (three ELIOT) and one was Grade 3. The post-radiotherapy risk in the EBRT arm
      to develop at least Grade 1 fibrosis was 19 times higher than in the ELIOT one
      (OR: 19.20; 95%CI: 6.46-57.14) and 6 times higher to develop at least Grade 2
      (OR: 5.70; 95%CI: 1.56-20.76). In conclusion, CT detected pulmonary fibrosis in
      patients treated with ELIOT is significantly less frequent compared to patients
      treated with EBRT.

PMID- 21728390
TI  - A two-step optimization method for improving multiple brain lesion treatments
      with robotic radiosurgery.
AB  - Planning robotic radiosurgery treatments for multiple (n > 3) metastatic brain
      lesions is challenging due to the need of satisfying a large number of dose
      volume constraints and the requirement of prescribing different dose levels to
      individual targets. In this study, we developed a sequential two-step
      optimization technique to improve the planning quality of such treatments. In
      contrast to the conventional approach of where all targets are simultaneously
      planned, we have developed a two-step optimization method. In this method, the
      first step was to create treatment plans for individual targets. In the second
      step, the 3D dose matrices associated with each plan were exported to Dicom-RT
      digital files and subsequently optimized. For the optimization, a singular-value
      decomposition (SVD) algorithm was implemented to minimize the dose interferences
      among different targets. Finally, we compared the optimized treatment plans with
      the treatment plans created using the conventional method to determine the
      effectiveness of the new method. Large improvements in target dose distributions
      as well as normal brain sparing were found for the two-step optimization
      treatment plans as compared with the conventional treatment plans. The two-step
      optimization significantly lowered the volume of normal brain receiving
      relatively low doses. For example, the normal brain volume receiving 12-Gy was
      reduced by averaged 42% (range 34%-47%) with the two-step optimization. Such
      improvements generally enlarged with increasing number of targets being treated
      regardless of target sizes. Of note, normal brain dose was found to increase non
      linearly with increasing number of targets. In summary, a two-step optimization
      technique is demonstrated to significantly improve the treatment plan quality as
      well as reduce the planning effort for multi-target robotic radiosurgery.

PMID- 21728391
TI  - Cryosurgery for treatment of subcutaneously xenotransplanted tumors in rats and
      its effect on cellular immunity.
AB  - Cryosurgery has shown encouraging therapeutic effects on some solid tumors but
      its effect on the cellular immunity remains unclear. We developed a
      subcutaneously xenotransplanted tumor model in SD rats to directly evaluate the
      immune response by detecting the serum cytokine levels, T-cell responses to tumor
      derived antigens, and the cytolytic activity of peripheral blood mononuclear
      cells against the W256 cancer line with apoptosis of cells being detected using
      TUNEL method. 66 SD rats were divided into 2 groups with group A having 36 rats
      and group B having 30 rats. 30 rats in group B were equally divided into 3
      groups, tumor group B, cryosurgery group B and surgery group B, with 10 rats
      each. 36 rats in group A were equally divided into 2 groups, cryosurgery group A
      and tumor group A and treatment was done accordingly. The results showed that
      cryosurgery induced not only destruction of the tumor cells but also cell
      apoptosis around the cryosurgery foci. The apoptosis ratio reached the peak 12 h
      after cryosurgery, with an apoptosis rate of (68.28 +/- 7.85)% .Compared with
      surgical resection that caused significant reduction in CD31 and CD41 cell
      percentages, cryosurgery resulted in significantly increased percentages of CD31
      and CD41 cells (P < 0.05) with a relative increase of the CD41/CD81 cell ratio.
      However, sIL-2R level of peripheral blood of rats in cryosurgery group which
      decreased more rapidly than that in surgery group over time was significantly
      different 3 and 5 weeks after treatment compared to surgery group (P < 0.01).
      Moreover, cytotoxicity of mononuclear cell was significantly enhanced after
      cryosurgery, which is significantly higher in cryosurgery group (P = 0.05). These
      results demonstrate that in addition to tumor cell destruction, cryosurgery also
      results in enhanced cellular immunity and antitumor immune response of the rats
      with subcutaneously xenotransplanted tumor, suggesting the great potential of
      argon-helium cryosurgery in clinical management.

PMID- 21728392
TI  - The improvement of irreversible electroporation therapy using saline-irrigated
      electrodes: a theoretical study.
AB  - Irreversible electroporation (IRE) is a novel therapy used to ablate tumors with
      high-field electric pulses applied in short durations. It is important to reduce
      the generation of heat in IRE to avoid the harmful effects of thermal damage. The
      objective of this simulation study was to examine the effects of saline
      irrigation in the reduction of heat upon electrodes used in IRE treatment of
      hepatocellular carcinoma. We used a two dimensional Finite Element Model of a
      tumor in a liver with electrodes placed at the center of the tumor. We simulated
      a typical electroporation protocol with varying thicknesses and conductivities of
      the saline layer, and we observed the maximum temperature and the distribution of
      the electric field and temperature in the tissue. Our results showed that the
      maximum temperature in the tissue decreases with the use of saline, but the
      surface area of the tumor that could potentially be thermally damaged may
      increase with the thickness and conductivity of the saline. With the use of
      saline, one can achieve upwards of a 17% reduction of the maximum temperature at
      the electrodes. Also, the distribution of temperature and the electric field
      becomes more homogenous between the electrodes as the conductivity of the saline
      layer increases for all thicknesses of saline. We conclude that irrigating
      electrodes with saline may be an effective measure to enhance the efficacy of
      irreversible electroporation by reducing the maximum temperature at the
      electrodes and also improving the extent and distribution of the electric field
      in the tissue. However, the properties of the saline should be adjusted so as to
      limit the increase of thermal damage propagated in the tissue.

PMID- 21728393
TI  - Anti-angiogenesis by lentivirus-mediated small interfering RNA silencing of
      angiopoietin-2 gene in pancreatic carcinoma.
AB  - Angiopoietin-2 (Ang2) has been shown highly expressed in resected human
      pancreatic carcinoma samples, but the role of it is less clear. We were,
      therefore, interested in exploring the effects of Ang2 silencing on the
      angiogenesis and growth of pancreatic carcinoma. Lentivirus mediated Ang2 small
      hairpin RNA (LV-RNAi) were transfected into pancreatic carcinoma cell line MIA
      PaCa-2. Three groups were designed in this study: the control group (Mia PaCa-2
      cells), the LV-NC group (cells transfected with the control GFP-lentivirus) and
      the LV-RNAi group (cells transfected with LV-RNAi). The mRNA and protein level of
      Ang2 gene were detected by real-time polymerase chain reaction and Western blot
      respectively. MTT assay and Flow Cytometry were used to detect the cell growth
      and apoptosis. Anti-angiogenesis effect was measured by chick embryo
      chorioallantoic membrane (CAM) assay. In nude mice bearing tumors, after
      treatment with intratumoral injection of LV-RNAi, mice growth and tumor volume
      were observed, and the expression of Ang2, VEGF and CD34 were measured by
      immunohistochemistry. Compared with the control group and the LV-NC group, the
      mRNA and protein level of Ang2 gene were successfully knocked down in LV- RNAi
      group. Also the vessel count was decreased in CAM assay after LV-RNAi
      transfection. Meanwhile, no obvious cell viability and apoptosis changes were
      found in MTT assay and Flow Cytometry, respectively. LV-RNAi inhibited pancreatic
      carcinoma angio- genesis and growth by downregulating the expression of VEGF and
      CD34. These findings demonstrate that Ang2 gene silencing may exert a anti
      angiogenesis effect in vitro and in vivo, and Ang2 targeted gene therapy has the
      potential to serve as a novel way for pancreatic carcinoma treatment.

PMID- 21728394
TI  - Cost-effective and non-invasive automated benign and malignant thyroid lesion
      classification in 3D contrast-enhanced ultrasound using combination of wavelets
      and textures: a class of ThyroScanTM algorithms.
AB  - Ultrasound has great potential to aid in the differential diagnosis of malignant
      and benign thyroid lesions, but interpretative pitfalls exist and the accuracy is
      still poor. To overcome these difficulties, we developed and analyzed a range of
      knowledge representation techniques, which are a class of ThyroScanTM algorithms
      from Global Biomedical Technologies Inc., California, USA, for automatic
      classification of benign and malignant thyroid lesions. The analysis is based on
      data obtained from twenty nodules (ten benign and ten malignant) taken from 3D
      contrast-enhanced ultrasound images. Fine needle aspiration biopsy and histology
      confirmed malignancy. Discrete Wavelet Transform (DWT) and texture algorithms are
      used to extract relevant features from the thyroid images. The resulting feature
      vectors are fed to three different classifiers: K-Nearest Neighbor (K-NN),
      Probabilistic Neural Network (PNN), and Decision Tree (DeTr). The performance of
      these classifiers is compared using Receiver Operating Characteristic (ROC)
      curves. Our results show that combination of DWT and texture features coupled
      with K-NN resulted in good performance measures with the area of under the ROC
      curve of 0.987, a classification accuracy of 98.9%, a sensitivity of 98%, and a
      specificity of 99.8%. Finally, we have proposed a novel integrated index called
      Thyroid Malignancy Index (TMI), which is made up of texture features, to diagnose
      benign or malignant nodules using just one index. We hope that this TMI will help
      clinicians in a more objective detection of benign and malignant thyroid lesions.

PMID- 21728395
TI  - Expression of IGF-1R in colorectal polyps and its role in colorectal
      carcinogenesis.
AB  - Insulin-like Growth Factor Receptor 1 (IGF-1R) may play a role in the neoplastic
      progression of colorectal cancer because it is related to both cellular
      proliferation and differentiation. The aim of this study was to further elucidate
      the role of IGF-1R in colorectal carcinogenesis by evaluating IGF-1R expression
      in different types of precancerous colorectal polyps and comparing its expression
      to normal mucosa and colorectal carcinoma. A total of 47 colorectal polyps and
      their respective adjacent normal mucosa were collected from 32 patients. In
      addition, 20 colorectal adenocarcinoma tissues were obtained from patients
      undergoing colorectal resection, and 12 normal non-malignant colorectal mucosal
      tissues collected from outpatients served as the control group. The pit patterns
      of polyps were classified by the Kudo classification scheme through magnifying
      chromoendoscopy. Immunohistochemistry and quantitative real-time RT-PCR were
      utilized for expression analysis of IGF-1R in colorectal mucosa, polyps, and
      adenocarcinoma tissue. The results of immunohistochemistry showed no significant
      differences in IGF-1R expression in inflammatory polyps compared with their
      surrounding normal mucosa by the Mann-Whitney U test (p=0.251); however, tubular
      adenoma and villous adenoma tissues exhibited significantly higher levels of IGF
      1R expression (p=0.000). The results of real-time RT-PCR showed that IGF-1R was
      transcribed at a high level in colorectal adenomatous polyps and adenocarcinoma
      compared with their respective paired normal mucosa. Spearman's rank correlation
      two-variable analysis was used to demonstrate a significant correlation between
      the expression of IGF-1R and neoplastic progression from normal mucosa to
      adenomatous polyps and finally to colorectal cancer (r=0.574, p=0.000). This
      study suggests that the expression of IGF-1R correlates with the degree of
      carcinogenesis. In addition, these results demonstrated that there is a
      significant correlation between the level of IGF-1R expression and pit patterns
      of polyps (r=0.432, p=0.002). Thus, IGF-1R might be a factor in the morphological
      change of colorectal mucosal crypts, and it may play an important role in the
      growth and malignant transformation of precancerous polyps. These results suggest
      that IGF-1R can be considered a biomarker for the stage and risk of
      carcinogenesis during neoplastic initiation and progression along the colorectal
      normal mucosa-polyp-cancer sequence. Inhibitors of IGF-1R are not only a
      promising targeted anticancer strategy, but also a possible option for the
      chemoprevention of colorectal cancer.

PMID- 21728396
TI  - Emotion-cognition interaction in people at familial high risk for schizophrenia:
      the impact of sex differences.
AB  - Cognitive deficits are fundamental to schizophrenia, and research suggests that
      negative emotion abnormally interferes with certain cognitive processes in those
      with the illness. To a lesser extent, cognitive impairment is found in persons at
      risk for schizophrenia, but there is limited research on the impact of emotion on
      cognitive processing in at-risk groups. It is unknown whether interference of
      negative emotion precedes illness and contributes to vulnerability for the
      disorder. We studied the extent to which negative emotional information
      interferes with working memory in 21 adolescent and young adult first-degree
      relatives of people with schizophrenia and 22 community controls. Groups were
      comparable in age, sex, education, ethnicity, and socioeconomic status. Primary
      measures were n-back tasks varying in cognitive load (1-back, 2-back, 3-back)
      with emotional faces (neutral, happy, fearful) as stimuli. The control group's
      response times (RTs) and the women's RTs, regardless of group, differed depending
      on the emotion condition. In contrast, the RTs of the relatives and of the men,
      regardless of group, did not differ by emotion. This study is the first to
      examine emotion-cognition interactions in relatives of individuals with
      schizophrenia. Reduced efficiency in processing emotional information may
      contribute to a greater vulnerability for schizophrenia that may be heightened in
      men. Additional research with larger samples of men and women is needed to test
      these preliminary findings.

PMID- 21728397
TI  - Reaping the benefits of task conflict in teams: the critical role of team
      psychological safety climate.
AB  - Past research suggests that task conflict may improve team performance under
      certain conditions; however, we know little about these specific conditions. On
      the basis of prior theory and research on conflict in teams, we argue that a
      climate of psychological safety is one specific context under which task conflict
      will improve team performance. Using evidence from 117 project teams, the present
      research found that psychological safety climate moderates the relationship
      between task conflict and performance. Specifically, task conflict and team
      performance were positively associated under conditions of high psychological
      safety. The results support the conclusion that psychological safety facilitates
      the performance benefits of task conflict in teams. Theoretical implications and
      suggestions for future research are discussed.

PMID- 21728398
TI  - When feeling bad leads to feeling good: guilt-proneness and affective
      organizational commitment.
AB  - The authors posit that higher levels of guilt-proneness are associated with
      higher levels of affective organizational commitment. To explain this
      counterintuitive link, the authors suggest that a dispositional tendency to feel
      guilt motivates individuals to exert greater effort on their work-related tasks
      that, in turn, strengthens their affinity for the organization. The authors
      tested this idea using a laboratory study and field data from 2 samples of
      working adults. Individuals who are more guilt-prone reported higher levels of
      organizational attachment compared with less guilt-prone individuals.
      Furthermore, mediation analyses indicate that the link between guilt-proneness
      and affective commitment is driven by greater task effort. The authors discuss
      the implications of these findings for understanding the affective drivers of
      commitment in organizations.

PMID- 21728399
TI  - A meta-analysis of the effect of cognitive bias modification on anxiety and
      depression.
AB  - Cognitive biases have been theorized to play a critical role in the onset and
      maintenance of anxiety and depression. Cognitive bias modification (CBM), an
      experimental paradigm that uses training to induce maladaptive or adaptive
      cognitive biases, was developed to test these causal models. Although CBM has
      generated considerable interest in the past decade, both as an experimental
      paradigm and as a form of treatment, there have been no quantitative reviews of
      the effect of CBM on anxiety and depression. This meta-analysis of 45 studies
      (2,591 participants) assessed the effect of CBM on cognitive biases and on
      anxiety and depression. CBM had a medium effect on biases (g = 0.49) that was
      stronger for interpretation (g = 0.81) than for attention (g = 0.29) biases. CBM
      further had a small effect on anxiety and depression (g = 0.13), although this
      effect was reliable only when symptoms were assessed after participants
      experienced a stressor (g = 0.23). When anxiety and depression were examined
      separately, CBM significantly modified anxiety but not depression. There was a
      nonsignificant trend toward a larger effect for studies including multiple
      training sessions. These findings are broadly consistent with cognitive theories
      of anxiety and depression that propose an interactive effect of cognitive biases
      and stressors on these symptoms. However, the small effect sizes observed here
      suggest that this effect may be more modest than previously believed.

PMID- 21728400
TI  - Effectiveness of motivational interviewing interventions for adolescent substance
      use behavior change: a meta-analytic review.
AB  - OBJECTIVE: This study was designed to quantitatively evaluate the effectiveness
      of motivational interviewing (MI) interventions for adolescent substance use
      behavior change. METHOD: Literature searches of electronic databases were
      undertaken in addition to manual reference searches of identified review
      articles. Databases searched include PsycINFO, PUBMED/MEDLINE, and Educational
      Resources Information Center. Twenty-one independent studies, representing 5,471
      participants, were located and analyzed. RESULTS: An omnibus weighted mean effect
      size for all identified MI interventions revealed a small, but significant,
      posttreatment effect size (mean d = .173, 95% CI [.094, .252], n = 21). Small,
      but significant, effect sizes were observed at follow-up suggesting that MI
      interventions for adolescent substance use retain their effect over time. MI
      interventions were effective across a variety of substance use behaviors, varying
      session lengths, and different settings, and for interventions that used
      clinicians with different levels of education. CONCLUSIONS: The effectiveness of
      MI interventions for adolescent substance use behavior change is supported by
      this meta-analytic review. In consideration of these results, as well as the
      larger literature, MI should be considered as a treatment for adolescent
      substance use.

PMID- 21728401
TI  - Associations among experiential avoidance, couple adjustment, and interpersonal
      aggression in returning Iraqi war veterans and their partners.
AB  - OBJECTIVE: The purpose of the present study was to examine the role of
      experiential avoidance (EA) in relationship adjustment, psychological aggression,
      and physical aggression among military couples. METHOD: The sample was composed
      of 49 male soldiers who recently returned from deployment to Iraq and their
      female partners. As part of a larger study, participants completed self-report
      measures of emotional avoidance (EA; Acceptance and Action Questionnaire-II),
      relationship adjustment (Dyadic Adjustment Scale), and conflict (Conflict Tactics
      Scale-2). Data from men and women were simultaneously modeled with the actor
      partner interdependence model. RESULTS: Men's EA was associated with decreases in
      relationship adjustment and increases in physical aggression perpetration and
      victimization. For women, relationship adjustment was not associated with EA, but
      greater EA among women was associated with decreased relationship adjustment for
      male partners. Associations among EA and psychological aggression were
      nonsignificant. CONCLUSIONS: These data provide evidence that EA may play a
      critical role in the relationships of couples following deployment and highlight
      the importance of targeting EA in couple therapy.

PMID- 21728402
TI  - Extensions of the picture superiority effect in associative recognition.
AB  - Previous research has shown that the picture superiority effect (PSE) is seen in
      tests of associative recognition for random pairs of line drawings compared to
      pairs of concrete words (Hockley, 2008). In the present study we demonstrated
      that the PSE for associative recognition is still observed when subjects have
      correctly identified the individual items of each pair as old (Experiment 1), and
      that this effect is not due to rehearsal borrowing (Experiment 2). The PSE for
      associative recognition also is shown to be present but attenuated for mixed
      picture-word pairs (Experiment 3), and similar in magnitude for pairs of simple
      black and white line drawings and coloured photographs of detailed objects
      (Experiment 4). The results are consistent with the view that the semantic
      meaning of nameable pictures is activated faster than that of words thereby
      affording subjects more time to generate and elaborate meaningful associations
      between items depicted in picture form.

PMID- 21728403
TI  - [Variations of encoding and false memories in recall].
AB  - This article presents two experiments using the DRM paradigm and examining the
      effects of variations in the depth of processing on the occurrence of false
      memories at recall. Contrary to what is generally observed, the results of the
      first experiment indicate that deep processing, maximizing the possibility of
      implication of distinctive characteristics, leads to an increase of the recall of
      hits without increasing the recall of lures. The second experiment uses
      instructions of inclusion requiring participants to recall not only the presented
      items but also all the words that were activated in memory both during the
      encoding and retrieval phases. These instructions, which deactivate the strategy
      of control of the source, support the notion that deep processing favours the
      activation of distinctive characteristics that facilitate the process of
      discrimination during the identification of the source.

PMID- 21728404
TI  - Lack of power enhances visual perceptual discrimination.
AB  - Powerless individuals face much challenge and uncertainty. As a consequence, they
      are highly vigilant and closely scrutinize their social environments. The aim of
      the present research was to determine whether these qualities enhance performance
      in more basic cognitive tasks involving simple visual feature discrimination. To
      test this hypothesis, participants performed a series of perceptual matching and
      search tasks involving colour, texture, and size discrimination. As predicted,
      those primed with powerlessness generated shorter reaction times and made fewer
      eye movements than either powerful or control participants. The results indicate
      that the heightened vigilance shown by powerless individuals is associated with
      an advantage in performing simple types of psychophysical discrimination. These
      findings highlight, for the first time, an underlying competency in perceptual
      cognition that sets powerless individuals above their powerful counterparts, an
      advantage that may reflect functional adaptation to the environmental challenge
      and uncertainty that they face.

PMID- 21728405
TI  - Semantic priming with product verification but not production.
AB  - Campbell and Reynvoet (2009) found that time to name a single-digit target was
      about 8 ms faster if preceded by a near prime (+/-1) compared to a far prime (at
      least +/-3) when prime-digit pairs were interleaved with number comparisons (9?3;
      name larger) and not when they were interleaved with multiplication problems
      (9*3; state product). This is consistent with the claim by previous researchers
      that magnitude comparison can enable a semantic pathway for digit naming whereas
      number-fact retrieval can inhibit it. To pursue this, the current study compared
      priming in the context of multiplication production (9*3=?) versus multiplication
      verification (e.g., 9*3=24, true or false). Multiplication production, but not
      verification, may inhibit semantic digit naming to reduce naming-related
      interference with verbal number production. Indeed, semantic priming of digit
      naming occurred only in verification and not production blocks. This supports the
      conclusion that multiplication production can inhibit semantic mediation of digit
      naming, which is enabled in other number processing tasks (e.g., comparison,
      verification) that do not compete with naming for verbal number production
      processes.

PMID- 21728406
TI  - Sharing morphemes without sharing meaning: production and comprehension of German
      verbs in the context of morphological relatives.
AB  - We investigated the impact of derived German verbs on the production and
      recognition of morphologically related simple verbs. In order to disentangle
      effects of morphological, semantic, and phonological relatedness, target verbs
      were combined (e.g., zahlen--to count) with four context verbs: Two
      morphologically related context verbs that were either semantically transparent
      (verzahlen--to miscount) or semantically opaque (erzahlen--to tell), a
      semantically related (rechnen--to calculate) and a phonologically related (zahmen
      -to tame) context verb. Morphologically related complex verbs reduced picture
      naming latencies as well as lexical decision latencies. Semantically related
      verbs did not show any reliable effects. In production, morphological
      facilitation was almost four times larger than phonological facilitation. In
      comprehension, pure form overlap produced inhibition. We argue that in German,
      production and comprehension processes operate on morphologically decomposed
      lexical form representations. Independent from semantic transparency, complex
      verbs are broken down into their morphemes during comprehension and are assembled
      during production.

PMID- 21728407
TI  - Revisiting Fitts and Peterson (1964): width and amplitude manipulations to the
      reaching environment elicit dissociable movement times.
AB  - The classic theorem of Fitts (1954) asserts that the combined effects of movement
      amplitude and target width (index of difficulty: ID) define movement times (MTs)
      for goal-directed reaches. Moreover, Fitts' theorem states that reaches yielding
      the same ID produce equivalent MTs regardless of the response's amplitude and
      width combination. However, most work providing direct support for Fitts' theorem
      has employed short movement amplitudes and small target widths. Thus, no direct
      evidence supports the unitary nature of MT/ID relations across a range of
      amplitudes and widths used in contemporary studies of goal-directed reaching. To
      that end, we contrasted MT/ID relations for discrete reaches equated for movement
      ID but differing with respect to their amplitude (15.5, 19, 25.5, and 38 cm) and
      width (2, 3, 4, and 5 cm) requirements. Results show that amplitude and width
      manipulations yielded robust linear MT/ID relations; however, the slope of the
      MT/ID function was markedly steeper in the former (amplitude=92 ms; width=13 ms).
      Such findings indicate that the constituent elements of movement ID are
      dissociable and that the fixed parameter nature of Fitts' theorem cannot be
      applied to a continuous range of veridical movement amplitudes and target widths.

PMID- 21728408
TI  - Can balance efficacy be manipulated using verbal feedback?
AB  - Verbal feedback was used to alter balance efficacy to examine its effects on
      perceived and actual balance in young adults. Participants (N=61) completed a
      stance task, were randomized to either a high or low balance efficacy or control
      group, and then completed the same task. The results showed that balance efficacy
      was manipulated as the low balance efficacy group had decreases in balance
      efficacy. Although verbal feedback did not alter balance efficacy in the high
      balance efficacy group, perceptions of stability increased for these
      participants. No changes in actual balance were found. The nature of verbal
      feedback may differentially influence balance-related cognitions during a
      challenging stance task in young adults.

PMID- 21728409
TI  - Distinctiveness and repetition in item recognition.
AB  - We scrutinized the hypothesis that the distinctiveness of unrepeated stimuli
      yields an enhancement of their memorability, when contrasted with repeated
      stimuli. In three conditions of a variant of von Restorff's (1933) isolation
      paradigm, unrepeated stimuli were respectively rendered either distinctive, by
      intermixing them with repeated stimuli from a different category, or
      nondistinctive, by having both unrepeated and repeated items originate in the
      same category or categories. The recognition-memory strength difference between
      unrepeated and repeated stimuli, in terms of a signal-detection measure of
      sensitivity, was less when the unrepeated stimuli were distinctive than when they
      were not distinctive. This implies that the relative weakness of unrepeated
      stimuli may be offset by distinctiveness that accrues from their infrequency.
      These findings are considered with reference to contemporary theoretical
      treatments of distinctiveness.

PMID- 21728410
TI  - Inferential reasoning by exclusion in children (Homo sapiens).
AB  - The cups task is the most widely adopted forced-choice paradigm for comparative
      studies of inferential reasoning by exclusion. In this task, subjects are
      presented with two cups, one of which has been surreptitiously baited. When the
      empty cup is shaken or its interior shown, it is possible to infer by exclusion
      that the alternative cup contains the reward. The present study extends the
      existing body of comparative work to include human children (Homo sapiens). Like
      chimpanzees (Pan troglodytes) that were tested with the same equipment and near
      identical procedures, children aged three to five made apparent inferences using
      both visual and auditory information, although the youngest children showed the
      least-developed ability in the auditory modality. However, unlike chimpanzees,
      children of all ages used causally irrelevant information in a control test
      designed to examine the possibility that their apparent auditory inferences were
      the product of contingency learning (the duplicate cups test). Nevertheless, the
      children's ability to reason by exclusion was corroborated by their performance
      on a novel verbal disjunctive syllogism test, and we found preliminary evidence
      consistent with the suggestion that children used their causal-logical
      understanding to reason by exclusion in the cups task, but subsequently treated
      the duplicate cups information as symbolic or communicative, rather than causal.
      Implications for future comparative research are discussed.

PMID- 21728411
TI  - Exploring actor-partner interdependence in family therapy: whose view (parent or
      adolescent) best predicts treatment progress?
AB  - Predictions of family therapy outcome consistently vary depending on which client
      rates the alliance. We used the actor-partner interdependence model (Kenny,
      Kashy, & Cook, 2006) to test the interdependence of parents' and adolescents'
      ratings of alliance, session depth/value, and improvement-so-far after Sessions
      3, 6, and 9. Initial analyses found trivial between-therapists variance;
      therefore, a 3-level hierarchical model partitioned the variance in these
      variables into between families, between family members, and between session
      components. For alliance and session depth, results showed a significant parent
      actor effect and a significant adolescent partner effect. Specifically, when
      parents saw a stronger alliance, they also saw the session as more valuable, but
      when adolescents saw a stronger alliance, their parents saw the session as less
      valuable. Both the parents' and the adolescents' improvement scores showed
      significant linear growth over time, and adolescents' alliance ratings were
      positively associated with their own and their parents' views of therapeutic
      progress.

PMID- 21728412
TI  - Development and validation of the Internalized Racial Oppression Scale for Black
      individuals.
AB  - This article describes the development and validation of the Internalized Racial
      Oppression Scale (IROS) for Black individuals in 2 studies using a total sample
      of 468 Black college students. The IROS is intended to measure the degree to
      which racial oppression is internalized and replicated by Black individuals in
      the United States. An exploratory factor analysis suggested a five-factor
      solution: Belief in the Biased Representation of History (BRH), Devaluation of
      the African Worldview and Motifs (DAW), Alteration of Physical Appearance (APA),
      Internalization of Negative Stereotypes (INS), and Hair Change (HC). Confirmatory
      factory analysis supported an adequate model fit of a four-factor model: BRH,
      APA, INS, and HC. All factors of the IROS were positively correlated with the Pre
      Encounter subscale of the Racial Identity Attitude Scale (RIAS-B; J. E. Helms &
      T. A. Parham, 1996), and 4 of the factors were negatively correlated with the
      Immersion/Emersion subscale of the RIAS-B. Four factors of the IROS were
      negatively correlated with all subscales and total scores of the African Self
      Consciousness Scale (J. A. Baldwin & Y. R. Bell, 1985). These results provide
      some support of the validity of the IROS.

PMID- 21728413
TI  - When feeling bad is expected to be good: emotion regulation and outcome
      expectancies in social conflicts.
AB  - According to the instrumental approach to emotion regulation, people may want to
      experience even unpleasant emotions to attain instrumental benefits. Building on
      value-expectancy models of self-regulation, we tested whether people want to feel
      bad in certain contexts specifically because they expect such feelings to be
      useful to them. In two studies, participants were more likely to try to increase
      their anger before a negotiation when motivated to confront (vs. collaborate
      with) a negotiation partner. Participants motivated to confront (vs. collaborate
      with) their partner expected anger to be more useful to them, and this
      expectation in turn, led them to try to increase their anger before negotiating.
      The subsequent experience of anger, following random assignment to emotion
      inductions (Study 1) or engagement in self-selected emotion regulation activities
      (Study 2), led participants to be more successful at getting others to concede to
      their demands, demonstrating that emotional preferences have important pragmatic
      implications.

PMID- 21728414
TI  - Pleasing frowns, disappointing smiles: an ERP investigation of counterempathy.
AB  - The biological predisposition to resonate emotionally with another person is
      regarded as a critical aspect of social interaction. There are, however,
      situations in which the emotional response to others is discordant with their
      emotional experience. Using event-related potentials, the present study
      investigated the neural underpinnings of this phenomenon, termed
      "counterempathy." Participants played a card game under the belief that they were
      playing jointly with another player who sat in an adjoining room and whose smiles
      and frowns in response to winning or losing in the game they could observe on a
      computer screen. Depending upon the experimental setting, the other player's
      facial expressions conveyed either of two opposing values to the participant. In
      the empathic setting, his emotional expressions were congruent with the
      participant's outcome (win or loss), whereas in the counterempathic setting, they
      indicated incongruent outcomes. Results revealed a reversed pattern of brain
      responses to facial expressions between congruent and incongruent conditions at
      ~170 ms (N170) over the temporal cortex. That is, N170 was sensitive to frowns in
      the congruent condition and to smiles in the incongruent condition, both
      indicating losses for the participant. Furthermore, frowns in the incongruent
      condition yielded larger medial frontal negativity (MFN) over the medial
      prefrontal cortex, which correlated with the subjective pleasantness about one's
      own winning in the incongruent condition. These findings demonstrate that (1)
      counterempathic responses are associated with modulation of early sensory
      processing of emotional cues, (2) that MFN is sensitive to the detection of
      another person's loss during positive inequity, and (3) that MFN is associated
      with a pleasant feeling during positive inequity, which is possibly related to
      "Schadenfreude."

PMID- 21728415
TI  - The effect of self-distancing on adaptive versus maladaptive self-reflection in
      children.
AB  - Although children and adolescents vary in their chronic tendencies to adaptively
      versus maladaptively reflect over negative feelings, the psychological mechanisms
      underlying these different types of self-reflection among youngsters are unknown.
      We addressed this issue in the present research by examining the role that self
      distancing plays in distinguishing adaptive versus maladaptive self-reflection
      among an ethnically and socioeconomically diverse sample of fifth-grade public
      schoolchildren. Children were randomly assigned to analyze their feelings
      surrounding a recent anger-related interpersonal experience from either a self
      immersed or self-distanced perspective. They then rated their negative affect and
      described in writing the stream of thoughts they experienced when they analyzed
      their feelings. Children's stream-of-thought essays were content analyzed for the
      presence of recounting statements, reconstruing statements, and blame
      attributions. Path analyses indicated that children who analyzed their feelings
      from a self-distanced perspective focused significantly less on recounting the
      "hot," emotionally arousing features of their memory (i.e., what happened to me?)
      and relatively more on reconstruing their experience. This shift in thought
      content--less recounting and more reconstruing--led children in the self
      distanced group to blame the other person involved in their recalled experience
      significantly less, which in turn led them to display significantly lower levels
      of emotional reactivity. These findings help delineate the psychological
      mechanisms that distinguish adaptive versus maladaptive forms of self-reflection
      over anger experiences in children. Their basic findings and clinical
      implications are discussed.

PMID- 21728416
TI  - We feel, therefore we are: emotion as a basis for self-categorization and social
      action.
AB  - Building on intergroup emotion research, we test the idea that intergroup emotion
      influences self-categorization. We report two studies using minimal (Study 1) and
      natural (Study 2) groups in which we measured participants' emotional reactions
      to a group-relevant event before manipulating the emotional reactions of other
      ingroup members and outgroup members (anger vs. happiness in Study 1; anger vs.
      indifference in Study 2). Results supported the hypotheses that (a) the fit
      between participants' own emotional reactions and the reactions of ingroup
      members would influence self-categorization, and (b) the specific content of
      emotional reactions would shape participants' willingness to engage in collective
      action. This willingness was greater when emotional reactions were not only
      shared with other group members, but were of anger (consistent with group-based
      action) rather than happiness or indifference (inconsistent with group-based
      action). Implications for the relationship between emotion and social identities
      are discussed.

PMID- 21728418
TI  - Workplace Triple P: A controlled evaluation of a parenting intervention for
      working parents.
AB  - This paper examined the effects of a parenting intervention targeting working
      parents called Workplace Triple P. The intervention targeted both parenting and
      work factors, focusing on key transition times (e.g., from home to work) and
      trained parents to more effectively manage these transitions. One-hundred-and
      twenty-one working parents with children ranging in age from 1-16 years were
      randomly assigned to either a Workplace Triple P condition (WPTP) or to a
      waitlist control condition (WLC). Results showed that parents who had received
      the intervention reported significantly lower levels on measures of personal
      distress and dysfunctional parenting; and higher levels of work commitment, work
      satisfaction, and self-efficacy. Implications for the delivery of parenting
      interventions as employee assistance programs are discussed along with how such
      interventions can enhance work and family life.

PMID- 21728419
TI  - Predicting married and cohabiting couples' futures from their descriptions of
      stepfamily life.
AB  - Stepfamily couples experience specific challenges early in their relationships,
      (e.g., reaching agreement on the role of the stepparent in parenting). The Oral
      History Interview for Stepfamilies (OHI-S) was developed to assess spouses'
      cognitive representations of their adaptation to these challenges. It was
      hypothesized that their responses would predict future relationship satisfaction
      and stability. One-hundred and 22 stepfamily couples completed the OHI-S and were
      assessed on relationship satisfaction and stability at Time 1 and 2.5 years later
      (Time 2). Time 2 relationship satisfaction and stability were both predicted by
      the OHI-S at Time 1. Couples' perceptions of the stepfamily and couple
      relationship predict separation, and suggest there is an opportunity for early
      intervention to enhance stepfamily couple relationships.

PMID- 21728420
TI  - Postplacement relationships between birth mothers and their romantic partners.
AB  - Using a mixed-methods approach, the understudied population of birth mothers who
      placed their infants for adoption 12-20 years ago was explored in the context of
      their romantic relationships. In a semistructured interview, 104 birth mothers
      answered detailed questions about their romantic relationships and adoption
      related experiences. All birth mothers had disclosed the adoption placement to
      their romantic partners, and most had done so early because they wanted to be
      truthful about their past. On average, the birth mothers were satisfied with
      their romantic relationships and almost half did not believe that the adoption
      had affected it. Regarding contact in the adoption, a majority of the birth
      mothers' romantic partners (63.5%) were not directly involved in contact with the
      adoptive family or adopted youth. Implications about how adoption is perceived
      and processed within intimate relationships are discussed.

PMID- 21728421
TI  - Identification of distinct depressive symptom trajectories in women following
      surgery for breast cancer.
AB  - OBJECTIVE: Depressive symptoms, common in breast cancer patients, may increase,
      decrease, or remain stable over the course of treatment. Most longitudinal
      studies have reported mean symptom scores that tend to obscure interindividual
      heterogeneity in the symptom experience. The identification of different
      trajectories of depressive symptoms may help identify patients who require an
      intervention. This study aimed to identify distinct subgroups of breast cancer
      patients with different trajectories of depressive symptoms in the first six
      months after surgery. METHOD: Among 398 patients with breast cancer, growth
      mixture modeling was used to identify latent classes of patients with distinct
      depressive symptom profiles. These profiles were identified based on Center for
      Epidemiological Studies-Depression (CES-D) scale scores completed just prior to
      surgery, and 1, 2, 3, 4, 5, and 6 months after surgery. RESULTS: Four latent
      classes of breast cancer patients with distinct depressive symptom trajectories
      were identified: Low Decelerating (38.9%), Intermediate (45.2%), Late
      Accelerating (11.3%), and Parabolic (4.5%) classes. Patients in the Intermediate
      class were younger, on average, than those in the Low Decelerating class. The
      Intermediate, Late Accelerating, and Parabolic classes had higher mean baseline
      anxiety scores compared to the Low Decelerating class. CONCLUSIONS: Breast cancer
      patients experience different trajectories of depressive symptoms after surgery.
      Of note, over 60% of these women were classified into one of three distinct
      subgroups with clinically significant levels of depressive symptoms.
      Identification of phenotypic and genotypic predictors of these depressive symptom
      trajectories after cancer treatment warrants additional investigation.

PMID- 21728422
TI  - Is self-concealment associated with acute and chronic pain?
AB  - OBJECTIVE: Self-concealment is the predisposition to hide negative personal
      information. The present research examined whether self-concealment was
      associated with acute and chronic pain. METHODS: In Study 1, undergraduate
      students (N = 44) completed an online questionnaire packet and then completed a
      cold-pressor task in the laboratory. In Study 2, individuals with chronic pain (N
      = 85) completed an online survey. RESULTS: Study 1: Trait self-concealment was
      negatively associated with pain tolerance. Study 2: Self-concealment of chronic
      pain (hiding aspects of one's chronic pain condition from others) was associated
      with higher levels of self-reported pain and lower psychological well-being,
      independent of disclosure of feelings regarding pain. Furthermore, this
      association was mediated by autonomy and competence needs. CONCLUSIONS: Self
      concealment was found to be associated with higher levels of pain in both healthy
      and chronic pain samples. Moreover, the findings also suggest that intervention
      methods using the self-determination theory framework (i.e., autonomy and
      competence supportive) might be effective for individuals with chronic pain.

PMID- 21728423
TI  - Choosing the number of clusters in Kappa-means clustering.
AB  - Steinley (2007) provided a lower bound for the sum-of-squares error criterion
      function used in K-means clustering. In this article, on the basis of the lower
      bound, the authors propose a method to distinguish between 1 cluster (i.e., a
      single distribution) versus more than 1 cluster. Additionally, conditional on
      indicating there are multiple clusters, the procedure is extended to determine
      the number of clusters. Through a series of simulations, the proposed methodology
      is shown to outperform several other commonly used procedures for determining
      both the presence of clusters and their number.

PMID- 21728424
TI  - Identifying a distinctive familial frequency band in reaction time fluctuations
      in ADHD.
AB  - OBJECTIVE: Patients with ADHD are typically more variable in their reaction times
      (RT) than control children. Signal processing analyses have shown that time
      series RT data of children with ADHD have a distinctive low frequency periodic
      structure suggestive of a pattern of occasional spontaneous performance lapses.
      Here we use a fine-grained analysis of spectral power across a broader frequency
      range to differentiate the periodic qualities of ADHD time series RT data from
      (a) 1/frequency noise, and (b) control performance. We also assess the
      familiality of these frequencies by using a proband-sibling design. METHOD:
      Seventy-one children with ADHD, one of their siblings, and 50 control
      participants completed a simple RT task. Power across the RT frequency spectrum
      was calculated. The frequencies significantly differentiating the two groups were
      identified. Familiality was assessed in two ways: first, by comparing probands
      with their unaffected siblings and controls, and, second, by investigating the
      siblings of neuropsychologically impaired and unimpaired children with ADHD.
      RESULTS: Analyses converged to highlight the potential importance of the .20-.26
      Hz band in differentiating the periodic structure of ADHD RT time series data
      from both 1/frequency noise and control performance. This frequency band also
      showed the strongest evidence of familiality. CONCLUSIONS: RT performance of
      children with ADHD had a distinctive periodic structure. The band identified as
      most differentiating and familial was at a higher frequency than in most previous
      reports. This highlights the importance of employing tasks with faster
      interstimulus intervals that will allow a larger portion of the frequency
      spectrum to be examined.

PMID- 21728425
TI  - Hearing loss and cognition in the Baltimore Longitudinal Study of Aging.
AB  - OBJECTIVE: To determine the relationship between hearing loss and cognitive
      function as assessed with a standardized neurocognitive battery. We hypothesized
      a priori that greater hearing loss is associated with lower cognitive test scores
      on tests of memory and executive function. METHOD: A cross-sectional cohort of
      347 participants >= 55 years in the Baltimore Longitudinal Study of Aging without
      mild cognitive impairment or dementia had audiometric and cognitive testing
      performed in 1990-1994. Hearing loss was defined by an average of hearing
      thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear. Cognitive testing
      consisted of a standardized neurocognitive battery incorporating tests of mental
      status, memory, executive function, processing speed, and verbal function.
      Regression models were used to examine the association between hearing loss and
      cognition while adjusting for confounders. RESULTS: Greater hearing loss was
      significantly associated with lower scores on measures of mental status (Mini
      Mental State Exam), memory (Free Recall), and executive function (Stroop Mixed,
      Trail Making B). These results were robust to analyses accounting for potential
      confounders, nonlinear effects of age, and exclusion of individuals with severe
      hearing loss. The reduction in cognitive performance associated with a 25 dB
      hearing loss was equivalent to the reduction associated with an age difference of
      6.8 years. CONCLUSION: Hearing loss is independently associated with lower scores
      on tests of memory and executive function. Further research examining the
      longitudinal association of hearing loss with cognitive functioning is needed to
      confirm these cross-sectional findings.

PMID- 21728426
TI  - Finding the self in metacognitive evaluations: metamemory and agency in
      nondemented elders.
AB  - OBJECTIVE: Metacognitive methodologies are used to examine the integrity of self
      referential processing in healthy adults and have been implemented to study
      disorders of the self-concept in neurologic and psychiatric populations. However,
      the extent to which metacognitive evaluations assess a uniquely self-evaluative
      capacity that cannot be explained fully by primary cognitive functions,
      demographics, or mood is not clear. The objective of the current study was to
      examine whether metamemory and a metacognitive test of agency shared a self
      referential association that would not be explained by cognition, demographics,
      or mood. METHOD: Thirty-eight nondemented older adults (Mini Mental State
      Examination [MMSE] >=24 and mean age = 68.13) participated in metacognitive
      testing and completed cognitive testing and mood questionnaires. Bivariate
      correlations were used to evaluate the association between metamemory and agency,
      and to determine the cognitive (memory, attention, and executive functioning),
      demographic (age and education), and mood (anxiety and depression) correlates of
      each. Correlates of metamemory and agency were then entered into linear
      regression models to determine whether any association between metacognitive
      measures remained. RESULTS: Metamemory was associated with agency judgments (n =
      27), specifically those on self-controlled rather than computer-controlled trials
      (r = .41, p = .03). Regression results supported a role for agency in predicting
      metamemory, above and beyond memory and education (beta = .39, p = .034).
      Metamemory was also an independent predictor of agency judgments (beta = .36, p =
      .049). CONCLUSIONS: The interrelation between metamemory and agency judgments
      suggests that metacognitive testing captures an important aspect of self
      referential processing not otherwise assessed in a standard cognitive evaluation
      and may provide unique information about self-evaluative capacities in clinical
      populations.

PMID- 21728427
TI  - Is the apolipoprotein e genotype a biomarker for mild cognitive impairment?
      Findings from a nationally representative study.
AB  - OBJECTIVE: Although the epsilon4 allele of the apolipoprotein E (APOE) genotype
      is a known risk factor for Alzheimer's dementia (AD), prior findings on whether
      it is also a risk factor for mild cognitive impairment (MCI) have been
      inconsistent. We tested two contrasting explanations: (a) an epsilon4-AD
      specificity hypothesis, and (b) a measurement insensitivity hypothesis. METHOD:
      The frequency of the epsilon4 allele was investigated in older adults (mean age >
      70) with various types of cognitive impairment (including MCI) and various types
      of dementia (including AD) with the aging, demographics, and memory study (ADAMS)
      of the National Institute on Aging's Health and Retirement Study (HRS). The ADAMS
      controls sources of Type I and Type II error that are posited in the epsilon4-AD
      specificity hypothesis and the measurement insensitivity hypothesis, and it is
      the only nationally representative data set on aging and cognitive impairment.
      RESULTS: epsilon4 was a reliable predictor of MCI, with a frequency of 32% in MCI
      subjects versus 20% in healthy control subjects. This link was specific to MCI
      because epsilon4 was not a risk factor for other forms of cognitive impairment
      without dementia. CONCLUSIONS: The results support the measurement insensitivity
      hypothesis rather than the epsilon4-AD specificity hypothesis and are consistent
      with recent research showing modest reductions in cognitive performance among
      normal functioning epsilon4 carriers.

PMID- 21728428
TI  - Interference from retrieval cues in Parkinson's disease.
AB  - OBJECTIVE: Existing studies on memory interference in Parkinson's disease (PD)
      patients have provided mixed results and it is unknown whether PD patients have
      problems in overcoming interference from retrieval cues. We investigated this
      issue by using a part-list cuing paradigm. In this paradigm, after the study of a
      list of items, the presentation of some of these items as retrieval cues hinders
      the recall of the remaining ones. METHOD: We tested PD patients' (n = 19) and
      control participants' (n = 16) episodic memory in the presence and absence of
      part-list cues, using initial-letter probes, and following either weak or strong
      serial associative encoding of list items. RESULTS: Both PD patients and control
      participants showed a comparable and significant part-list cuing effect after
      weak associative encoding (13% vs. 12% decrease in retrieval in part-list cuing
      vs. no part-list cuing -control- conditions in PD patients and control
      participants, respectively), denoting a similar effect of cue-driven interference
      in the two populations when a serial retrieval strategy is hard to develop.
      However, only PD patients showed a significant part-list cuing effect after
      strong associative encoding (20% vs. 5% decrease in retrieval in patients and
      controls, respectively). CONCLUSIONS: When encoding promotes the development of
      an effective serial retrieval strategy, the presentation of part-list cues has a
      specifically disruptive effect in PD patients. This indicates problems in
      strategic retrieval, probably related to PD patients' increased tendency to rely
      on external cues. Findings in control conditions suggest that less effective
      encoding may have contributed to PD patients' memory performance.

PMID- 21728429
TI  - Evidence for deficits on different components of theory of mind in Huntington's
      disease.
AB  - OBJECTIVE: The main aim of this study was to investigate the effects of
      Huntington's disease (HD) on cognitive and affective Theory of Mind (ToM)
      abilities. The relation of ToM performance and executive functions was also
      examined. METHOD: Eighteen HD patients, early in the course of the disease, and
      18 healthy volunteers matched for age and educational levels, were given two
      tasks: a nonverbal cognitive ToM task assessing attribution of intentions to
      others and a revised version of the 'Reading the Mind in the Eyes' test, which is
      an affective ToM task assessing the understanding of other people's mental states
      from their eyes. Participants were also given various executive tests. RESULTS:
      The two ToM tasks revealed a significant impairment of ToM abilities in HD
      patients. Executive functioning was impaired in the HD group and ToM performance
      on the attribution of intentions task was dependent on several executive
      processes. CONCLUSIONS: Our results are consistent with the idea that both
      cognitive and affective aspects of ToM could be impaired in HD patients,
      indicating that cortico-subcortical circuits are underlying higher social
      functions such as ToM. The results are also consistent with the idea that only a
      few executive mechanisms regulate the ToM abilities we tested in this work. They
      also provide a basis for the understanding of the disorganized behavior and the
      breakdown of interpersonal relationships in daily life after HD.

PMID- 21728430
TI  - Examining the nature of impairment in visual paired associate learning in
      amnestic mild cognitive impairment.
AB  - OBJECTIVE: Visual spatial learning is impaired in mild cognitive impairment (MCI)
      although the nature of this impairment is not clear. This study investigated the
      nature and magnitude of errors made by adults with amnestic MCI (aMCI) when
      learning pattern-location paired associations in a continuous manner. METHOD:
      Visual associate learning was measured using the Continuous Paired Associate
      Learning (CPAL) task in which 30 adults who met clinical criteria for aMCI and 30
      matched controls were required to learn a set of associations between patterns
      and locations across increasing memory loads (two, four, six, and eight).
      RESULTS: As hypothesized, the aMCI group made more total errors than controls for
      all memory loads above two. However, the rate of increase in errors with memory
      load in the aMCI group was approximately twice that for controls. CONCLUSIONS: In
      controls, errors on the CPAL task reflected almost exclusively difficulty in
      memory. In the aMCI group, errors on the CPAL reflected limitations in
      associative learning but also in short-term memory and response monitoring. These
      results suggest that impairments in specific aspects of executive function and
      working memory might contribute to poor performance on visual paired associate
      learning in aMCI.

PMID- 21728431
TI  - Evidence for selective inhibitory impairment in individuals with autism spectrum
      disorder.
AB  - OBJECTIVE: The social and communicative challenges faced by individuals with
      autism spectrum disorder (ASD) are often compounded by additional difficulties
      with executive function. It remains unclear, however, to what the extent
      individuals with ASD experienced impairment in inhibitory control. The objective
      of the present study was to assess the three main subtypes of executive
      inhibitory control within a single ASD sample thus providing new insight into the
      unique ASD-related pattern of sparing and impairment observed across different
      aspects of inhibitory control. METHOD: A sample of 28 children with ASD (mean age
      = 13.1 years) and a comparison group of 49 neurologically uncompromised children
      (mean age = 13.3 years) participated. A prepotent response inhibition task, a
      flanker visual filtering task, and a proactive interference memory task were used
      to evaluate prepotent response inhibition, resistance to distracter interference,
      and resistance to proactive interference, respectively. RESULTS: After accounting
      for individual differences in noninhibition abilities (e.g., processing speed)
      and overall level of functioning, there was no evidence of group-related
      differences in inhibitory performance on the prepotent response inhibition test
      or proactive interference test. ASD-related impairments in inhibitory control
      were evident, however, on the flanker visual filtering task. CONCLUSIONS: Taken
      together, the present findings indicate that ASD is associated with impairments
      in some, but not all, aspects of inhibitory control. Individuals with ASD appear
      to have difficulty ignoring distracting visual information, but prepotent
      response inhibition and resistance to proactive interference are relatively
      intact. The current findings also provide support for a multitype model of
      inhibitory control.

PMID- 21728432
TI  - Action and object processing in brain-injured speakers of Chinese.
AB  - OBJECTIVE: To see whether action and object processing across different tasks and
      modalities differs in brain-injured speakers of Chinese with varying fluency and
      lesion locations within the left hemisphere. METHOD: Words and pictures
      representing actions and objects were presented to a group of 33 participants
      whose native and/or dominant language was Mandarin Chinese: 23 patients with left
      hemisphere lesions due to stroke and 10 language-, age- and education-matched
      healthy control participants. A set of 120 stimulus items was presented to each
      participant in three different forms: as black and white line drawings (for
      picture-naming), as written words (for reading) and as aurally presented words
      (for word repetition). Patients were divided into groups for two separate
      analyses: Analysis 1 divided and compared patients based on fluency (Fluent vs.
      Nonfluent) and Analysis 2 compared patients based on lesion location (Anterior
      vs. Posterior). RESULTS: Both analyses yielded similar results: Fluent,
      Nonfluent, Anterior, and Posterior patients all produced significantly more
      errors when processing action (M = 0.73, SD = 0.45) relative to object (M = 0.79,
      SD = 0.41) stimuli, and this effect was strongest in the picture-naming task.
      CONCLUSIONS: As in our previous study with English-speaking participants using
      the same experimental design (Arevalo et al., 2007, Arevalo, Moineau, Saygin,
      Ludy, & Bates, 2005), we did not find evidence for a double-dissociation in
      action and object processing between groups with different lesion and fluency
      profiles. These combined data bring us closer to a more informed view of
      action/object processing in the brain in both healthy and brain-injured
      individuals.

PMID- 21728434
TI  - Relationships between work-home segmentation and psychological detachment from
      work: the role of communication technology use at home.
AB  - Employees can have difficulty mentally distancing themselves from work during off
      job time due to increasing use of communication technologies (e.g., e-mail, cell
      phone, etc.). However, psychological detachment from work during nonwork time is
      important for employee recovery and health. This study examined several
      antecedents of psychological detachment: work-home segmentation preference,
      perceived segmentation norm, and the use of communication technology at home.
      Results indicate that segmentation preference and segmentation norm were
      positively associated with psychological detachment. Further, technology use at
      home partially mediated these relationships. Findings indicate that segmenting
      work and nonwork roles can help employees detach and recover from work demands.
      In addition, findings show that the segmentation norm within a work group is
      associated with employee experiences outside of work. (PsycINFO Database Record
      (c) 2011 APA, all rights reserved).

PMID- 21728433
TI  - The PHLAME (Promoting Healthy Lifestyles: Alternative Models' Effects)
      firefighter study: testing mediating mechanisms.
AB  - This paper examines the mechanisms by which PHLAME (Promoting Healthy Lifestyles:
      Alternative Models' Effects), a health promotion intervention, improved healthy
      eating and exercise behavior among firefighters, a population at high risk for
      health problems due to occupational hazards. In a randomized trial, 397
      firefighters participated in either the PHLAME team intervention with their work
      shift or a control condition. Intervention sessions taught benefits of a healthy
      diet and regular exercise, and sought to improve social norms and social support
      from coworkers for healthy behavior. At posttest, team intervention participants
      had increased their fruit and vegetable consumption as compared to control
      participants. An increase in knowledge of fruit and vegetable benefits and
      improved dietary coworker norms partially mediated these effects. Exercise habits
      and VO2 max were related to targeted mediators but were not significantly changed
      by the team intervention. Partial support was found for both the action and
      conceptual theories underlying the intervention. Our findings illustrate how an
      effective program's process can be deconstructed to understand the underpinnings
      of behavior change and refine interventions. Further, fire stations may improve
      the health of firefighters by emphasizing the benefits of healthy diet and
      exercise behaviors while also encouraging behavior change by coworkers as a
      whole.

PMID- 21728435
TI  - Effects of psychological hardiness, job demands, and job control on sickness
      absence: a prospective study.
AB  - This study prospectively investigated the effects of psychological hardiness, job
      control, and job demands on medically certified sickness absence. Data from a
      questionnaire survey were combined with archival data for sickness absence among
      7,239 civilian and military employees of the Norwegian Armed Forces (84.3% male,
      69.8% military). A 2-component hurdle regression was used in the statistical
      analyses of the sickness absence data. After controlling for age, sex, and
      baseline absence, hardiness predicted both the likelihood of having any sickness
      absence (odds ratio = 0.97) and the number of absence spells (a 6.5% decrease in
      the expected count for 1 standard deviation change in hardiness). In addition, an
      interaction was found among hardiness, job control, and psychological demands.
      When demands were high, high job control was associated with more absence among
      employees with low levels of hardiness. Together, these findings point to
      hardiness as an important individual resource in relation to health, and that it
      is necessary to consider individual differences when examining the effects of
      work characteristics.

PMID- 21728436
TI  - Why do overqualified incumbents deviate? Examining multiple mediators.
AB  - In the modern marketplace, especially when unemployment is high, more and more
      Americans find themselves overqualified (i.e., possessing more competencies than
      the job requires). Using and extending person-environment fit theory and the
      stressor-emotion model of counterproductive work behaviors (CWBs), we examine
      whether overqualified employees are more likely to display CWBs than employees
      who feel their positions match their qualification levels. Further, we examine
      why overqualified employees may behave in counterproductive ways and compare the
      empirical viability of several theoretically derived competing mediators. Based
      on data from a sample of full-time employees (n = 215), we found that consistent
      with the theoretical frameworks, overqualified incumbents display nondesirable
      counterproductive work behaviors because they become cynical about the
      meaningfulness of their activities. We further show that although poor person-job
      fit or inadequate psychological contracts can motivate such misbehavior, cynicism
      dominates as a reason for why overqualified employees engage in counterproductive
      work behaviors.

PMID- 21728437
TI  - Work-family enrichment and job performance: a constructive replication of
      affective events theory.
AB  - Based on affective events theory (AET), we hypothesize a four-step model of the
      mediating mechanisms of positive mood and job satisfaction in the relationship
      between work-family enrichment and job performance. We test this model for both
      directions of enrichment (work-to-family and family-to-work). We used two samples
      to test the model using structural equation modeling. Results from Study 1, which
      included 240 full-time employees, were replicated in Study 2, which included 189
      matched subordinate-supervisor dyads. For the work-to-family direction, results
      from both samples support our conceptual model and indicate mediation of the
      enrichment-performance relationship for the work-to-family direction of
      enrichment. For the family-to-work direction, results from the first sample
      support our conceptual model but results from the second sample do not. Our
      findings help elucidate mixed findings in the enrichment and job performance
      literatures and contribute to an understanding of the mechanisms linking these
      concepts. We conclude with a discussion of the practical and theoretical
      implications of our findings.

PMID- 21728438
TI  - The moderating role of cognitive control deficits in the link from emotional
      dissonance to burnout symptoms and absenteeism.
AB  - The present study examines whether cognitive control deficits (CCDs) as a
      personal vulnerability factor amplify the relationship between emotional
      dissonance (ED; perceived discrepancy between felt and expressed emotions) and
      burnout symptoms (emotional exhaustion and depersonalization) as well as
      absenteeism. CCDs refer to daily failures and impairments of attention
      regulation, impulse control, and memory. The prediction of the moderator effect
      of CCDs draws on the argument that portraying emotions which are not genuinely
      felt is a form of self-regulation taxing and depleting a limited resource
      capacity. Interindividual differences in the resource capacity are reflected by
      the measure of CCDs. Drawing on two German samples (one cross-sectional and one
      longitudinal sample; NTOTAL = 645) of service employees, the present study
      analyzed interactive effects of ED and CCDs on exhaustion, depersonalization, and
      two indicators of absenteeism. As was hypothesized, latent moderated structural
      equation modeling revealed that the adverse impacts of ED on both burnout
      symptoms and absence behavior were amplified as a function of CCDs. Theoretical
      and practical implications of the present results will be discussed.

PMID- 21728439
TI  - Adaptation and readaptation to different shift work schedules measured with sleep
      diary and actigraphy.
AB  - In this study we examine sleep during adaptation and readaptation to different
      shift work schedules in the offshore oil industry. The sleep of 19 offshore
      workers was assessed daily for 1 week before, during the work period, and for 1
      week after 3 different work schedules: (1) day (14 consecutive days of work), (2)
      night (14 consecutive nights of work), and (3) swing shift work (first 7 nights
      with night work then 7 days of day work). The workers' sleep was assessed for 84
      days. Actigraphy and sleep diary estimates of sleep was applied assessing: (1)
      adaptation to offshore shift work, (2) sleep across the 2 offshore work weeks,
      and (3) readaptation after the work period. Regarding adaptation, sleep
      efficiency was higher when working day than night and swing shift the first week
      of work. Sleep quality was better during swing than regular day/night shifts the
      first week of work. Total sleep time was longer during day and night shift than
      swing shift across the 2 work weeks. Sleep efficiency, based on sleep diaries,
      was higher during day than night and swing shift during the 2 work weeks. There
      were no significant differences between the shifts in readaptation in terms of
      sleep. To conclude, adaptation to swing shift was more difficult than adaptation
      to regular day and night shifts in terms of sleep. Readaptation to day work after
      1 week of night work affected sleep negatively. There were no differences between
      the shift schedules the week after the work period.

PMID- 21728440
TI  - A 35-year follow-up study on burnout among Finnish employees.
AB  - This three-wave 35-year prospective study used the Job Demands-Resources model
      and life course epidemiology to examine how life conditions in adolescence (1961
      1963) through achieved educational level and working conditions in early
      adulthood (1985) may be indirectly related to job burnout 35 years later (1998).
      We used data (N = 511) from the Finnish Healthy Child study (1961-1963) to
      investigate the hypothesized relationships by employing structural equation
      modeling analyses. The results supported the hypothesized model in which both
      socioeconomic status and cognitive ability in adolescence (1961-1963) were
      positively associated with educational level (measured in 1985), which in turn
      was related to working conditions in early adulthood (1985). Furthermore, working
      conditions (1985) were associated with job burnout (1998) 13 years later.
      Moreover, adult education (1985) and skill variety (1985) mediated the
      associations between original socioeconomic status and cognitive ability, and
      burnout over a 35-year time period. The results suggest that socioeconomic,
      individual, and work-related resources may accumulate over the life course and
      may protect employees from job burnout.

PMID- 21728441
TI  - On the costs and benefits of emotional labor: a meta-analysis of three decades of
      research.
AB  - This article provides a quantitative review of the link of emotional labor
      (emotion-rule dissonance, surface acting, and deep acting) with well-being and
      performance outcomes. The meta-analysis is based on 494 individual correlations
      drawn from a final sample of 95 independent studies. Results revealed substantial
      relationships of emotion-rule dissonance and surface acting with indicators of
      impaired well-being (rhos between .39 and .48) and job attitudes (rhos between 
      .24 and -.40) and a small negative relationship with performance outcomes (rhos
      between -.20 and -.05). Overall, deep acting displayed weak relationships with
      indicators of impaired well-being and job attitudes but positive relationships
      with emotional performance and customer satisfaction (rhos .18 and .37). A meta
      analytic regression analysis provides information on the unique contribution of
      emotion-rule dissonance, surface acting, and deep acting in statistically
      predicting well-being and performance outcomes. Furthermore, a mediation analysis
      confirms theoretical models of emotional labor which suggest that surface acting
      partially mediates the relationship of emotion-rule dissonance with well-being.
      Implications for future research as well as pragmatic ramifications for
      organizational practices are discussed in conclusion.

PMID- 21728442
TI  - Violate my beliefs? Then you're to blame! Belief content as an explanation for
      causal attribution biases.
AB  - We examined the extent to which the content of beliefs about appropriate behavior
      in social situations influences blame attributions for negative outcomes in
      relationship situations. Young, middle-aged, and older adults indicated their
      level of agreement to a set of traditional and nontraditional beliefs. Five
      months later, we assessed the degree to which these same individuals blamed
      traditional and nontraditional characters who violated their beliefs in 12 social
      conflict situations. Older adults held more traditional beliefs regarding
      appropriate relationship behaviors (e.g., the acceptability of premarital sex).
      Individual differences in the content of one's beliefs were needed to understand
      age-related patterns in blame attributions; for example, adherence to traditional
      beliefs about appropriate relationship behaviors led to higher responsibility and
      blame attributions toward characters behaving in ways that were inconsistent with
      these beliefs. Structural regression models showed that beliefs fully mediated
      the effects of working memory and need for closure on causal attributions and
      partially mediated the effects of age and religiosity on attributions. Personal
      identification with the characters had additional, independent effects on
      attributions. Findings are discussed from the theoretical perspective of a belief
      based explanation of social judgment biases.

PMID- 21728443
TI  - Aging and the structure and long-term stability of the internalizing spectrum of
      personality and psychopathology.
AB  - Structural psychopathology research has identified two broad factors-
      internalizing and externalizing--that account for comorbidity among many common
      mental disorders. Evaluating the utility of these factors for nosology, research,
      and treatment entails expanding beyond a cross-sectional understanding to how
      these factors evolve over time. We tested factorial invariance of internalizing
      in three age cohort groups--35 years and under (n = 1,729), 36-50 years (n =
      2,719), and over 50 years (n = 2,601)--as well as the long-term stability of
      internalizing within individuals. Internalizing showed a notable degree of
      invariance between cohorts and within cohorts over time; long-term internalizing
      stability was equivalently moderate-to-high in each cohort.

PMID- 21728444
TI  - Aging attitudes moderate the effect of subjective age on psychological well
      being: evidence from a 10-year longitudinal study.
AB  - Older subjective age is often associated with lower psychological well-being
      among middle-aged and older adults. We hypothesize that attitudes toward aging
      moderate this relationship; specifically, feeling older will predict lower well
      being among those with less favorable attitudes toward aging but not those with
      more favorable aging attitudes. We tested this with longitudinal data from the
      National Survey of Midlife Development in the United States-II assessing
      subjective age and psychological well-being over 10 years. As hypothesized older
      subjective age predicted lower life satisfaction and higher negative affect when
      aging attitudes were less favorable but not when aging attitudes were more
      favorable. Implications and future research directions are discussed.

PMID- 21728445
TI  - The moderating role of executive functioning in older adults' responses to a
      reminder of mortality.
AB  - In previous research, older adults responded to mortality salience (MS) with
      increased tolerance, whereas younger persons responded with increased
      punitiveness. One possible explanation for this is that many older adults adapt
      to challenges of later life, such as the prospect of mortality, by becoming more
      flexible. Recent studies suggest that positively oriented adaptation is more
      likely for older adults with high levels of executive functioning. Thus, we
      hypothesized that the better an older adult's executive functioning, the more
      likely MS would result in increased tolerance. Older and younger adults were
      randomly assigned to MS or control conditions, and then evaluated moral
      transgressors. As in previous research, younger adults were more punitive after
      reminders of mortality; executive functioning did not affect their responses.
      Among older adults, high functioning individuals responded to MS with increased
      tolerance rather than intolerance, whereas those low in functioning became more
      punitive.

PMID- 21728446
TI  - Tobacco psychopharmacology and public health policy: it takes a community.
AB  - This commentary is based upon the author's lecture given as the 2010 recipient of
      the award named in honor of Drs. Joseph V. Brady and Charles R. Schuster, given
      by the Psychopharmacology and Substance Abuse Division (Division 28) of the
      American Psychological Association (APA). The focus is on the contributions of
      many behavioral pharmacology researchers who collaborated very much in the spirit
      of an interactive community dedicated to the common cause of advancing science in
      service of public health. Division 28 and its members hold a prominent place in
      this account because, throughout the 1980s and 1990s, the Division was the lead
      scientific forum for bringing together researchers addressing the behavioral
      pharmacology of tobacco and nicotine. The commentary provides an overview of how
      advances utilizing animal and human models of dependence and withdrawal came to
      inform public health policy and more recently, tobacco product regulation. The
      commentary also recounts how efforts by the tobacco industry collided with those
      of nonindustry researchers, including Division 28 members, and how this was taken
      up in congressional hearings that addressed behavioral pharmacology research on
      tobacco. The review concludes with an overview of current challenges to
      behavioral pharmacology researchers to assist in guiding the regulation of
      tobacco products by the United States Food and Drug Administration and other
      national regulatory authorities, as well as guiding the implementation of the
      international tobacco treaty-the World Health Organization Framework Convention
      on Tobacco Control.

PMID- 21728447
TI  - Perspective taking as a means to overcome motivational barriers in negotiations:
      when putting oneself into the opponent's shoes helps to walk toward agreements.
AB  - Previous negotiation research predominantly focused on psychological factors that
      lead to suboptimal compromises as opposed to integrative agreements. Few studies
      systematically analyzed factors that impact the emergence of hurtful partial
      impasses (i.e., nonagreements on part of the issues). The present research
      investigates negotiators' egoistic motivation as a determinant for the emergence
      of partial impasses. In addition, the authors seek to demonstrate that
      perspective taking serves as a powerful tool to avoid impasses and to overcome
      egoistic impediments. Specifically, it was predicted that within an integrative
      context perspective-takers succeed to exchange concessions on low- versus high
      preference issues (i.e., logroll), thereby increasing their individual profits
      without inflicting hurtful losses upon their counterparts. Three studies were
      conducted to test these predictions. Study 1 reveals that whereas negotiators'
      egoistic motivation increases the risk of partial impasses, perspective taking
      alleviates this risk. Study 2 demonstrates that this beneficial effect of a
      perspective-taking mindset is limited to integrative negotiations and does not
      emerge in a distributive context, in which negotiators are constrained to achieve
      selfish goals by inflicting hurtful losses on their counterparts. Study 3
      confirms the assumption that in an integrative context egoistic perspective
      takers overcome the risk of impasses by means of logrolling. The findings of the
      present studies are discussed with respect to their contribution to research on
      negotiations, social motivation, and perspective taking.

PMID- 21728448
TI  - Self-esteem development from age 14 to 30 years: a longitudinal study.
AB  - We examined the development of self-esteem in adolescence and young adulthood.
      Data came from the Young Adults section of the National Longitudinal Survey of
      Youth, which includes 8 assessments across a 14-year period of a national
      probability sample of 7,100 individuals age 14 to 30 years. Latent growth curve
      analyses indicated that self-esteem increases during adolescence and continues to
      increase more slowly in young adulthood. Women and men did not differ in their
      self-esteem trajectories. In adolescence, Hispanics had lower self-esteem than
      Blacks and Whites, but the self-esteem of Hispanics subsequently increased more
      strongly, so that at age 30 Blacks and Hispanics had higher self-esteem than
      Whites. At each age, emotionally stable, extraverted, and conscientious
      individuals experienced higher self-esteem than emotionally unstable,
      introverted, and less conscientious individuals. Moreover, at each age, high
      sense of mastery, low risk taking, and better health predicted higher self
      esteem. Finally, the results suggest that normative increase in sense of mastery
      accounts for a large proportion of the normative increase in self-esteem.

PMID- 21728449
TI  - Friends with benefits: on the positive consequences of pet ownership.
AB  - Social support is critical for psychological and physical well-being, reflecting
      the centrality of belongingness in our lives. Human interactions often provide
      people with considerable social support, but can pets also fulfill one's social
      needs? Although there is correlational evidence that pets may help individuals
      facing significant life stressors, little is known about the well-being benefits
      of pets for everyday people. Study 1 found in a community sample that pet owners
      fared better on several well-being (e.g., greater self-esteem, more exercise) and
      individual-difference (e.g., greater conscientiousness, less fearful attachment)
      measures. Study 2 assessed a different community sample and found that owners
      enjoyed better well-being when their pets fulfilled social needs better, and the
      support that pets provided complemented rather than competed with human sources.
      Finally, Study 3 brought pet owners into the laboratory and experimentally
      demonstrated the ability of pets to stave off negativity caused by social
      rejection. In summary, pets can serve as important sources of social support,
      providing many positive psychological and physical benefits for their owners.

PMID- 21728450
TI  - Affective mediators of intergroup contact: a three-wave longitudinal study in
      South Africa.
AB  - Intergroup contact (especially cross-group friendship) is firmly established as a
      powerful strategy for combating group-based prejudice (Pettigrew & Tropp, 2006).
      Great advances have been made in understanding how contact reduces prejudice
      (Brown & Hewstone, 2005), highlighting the importance of affective mediators
      (Pettigrew & Tropp, 2008). The present study, a 3-wave longitudinal study
      undertaken among minority-status Colored high school children in South Africa (N
      = 465), explored the full mediation of the effects of cross-group friendships on
      positive outgroup attitudes, perceived outgroup variability, and negative action
      tendencies via positive (affective empathy) and negative (intergroup anxiety)
      affective mediators simultaneously. The target group was the majority-status
      White South African outgroup. As predicted, a bidirectional model described the
      relationship between contact, mediators, and prejudice significantly better over
      time than either autoregressive or unidirectional longitudinal models. However,
      full longitudinal mediation was only found in the direction from Time 1 contact
      to Time 3 prejudice (via Time 2 mediators), supporting the underlying tenet of
      the contact hypothesis. Specifically, cross-group friendships were positively
      associated with positive outgroup attitudes (via affective empathy) and perceived
      outgroup variability (via intergroup anxiety and affective empathy) and were
      negatively associated with negative action tendencies (via affective empathy).
      Following Pettigrew and Tropp (2008), we compared two alternative hypotheses
      regarding the relationship between intergroup anxiety and affective empathy over
      time. Time 1 intergroup anxiety was indirectly negatively associated with Time 3
      affective empathy, via Time 2 cross-group friendships. We discuss the theoretical
      and empirical contributions of this study and make suggestions for future
      research.

PMID- 21728451
TI  - Relationship-specific identification and spontaneous relationship maintenance
      processes.
AB  - Attractive alternative partners pose a relational threat to people in romantic
      relationships. Given that people are often limited in their time and energy,
      having the capacity to effortlessly respond to such relational threats is
      extremely useful. In 4 studies, we explored how people's identity in terms of
      their romantic relationship--their relationship-specific identity--affects their
      relationship-protective behaviors. We predicted that once a relationship becomes
      a part of one's sense of self, relationship maintenance responses are exhibited
      in a relatively fluid, spontaneous manner. In Study 1, we assessed the convergent
      and divergent validity of relationship-specific identification, demonstrating how
      it is associated with other relationship constructs. In Study 2, we found that
      less identified participants mentioned their relationship less than those high in
      relationship-specific identification, but only when interacting with an
      attractive member of their preferred sex. In Study 3, using a dot-probe visual
      cuing task, we found that when primed with an attractive member of their
      preferred sex, those low in relationship-specific identification gazed longer at
      attractive preferred-sex others compared to those high in relationship-specific
      identification. In Study 4, we found that relationship-specific identification
      was associated with relationship survival 1-3 years after the initial assessment.
      The present results demonstrate that relationship-specific identification
      predicts relatively spontaneous, pro-relationship responses in the face of
      relational threat.

PMID- 21728452
TI  - Anticipating evaluative social interactions involving persons with disabilities.
AB  - PURPOSE: Similar to other types of social interactions, the expected outcomes of
      interactions between persons with and without disabilities likely are influenced
      by global self-esteem such that individuals with high self-esteem should fare
      better than those with low self-esteem. The present set of laboratory studies
      examined whether simple and complex evaluative situations affect the role of self
      esteem when anticipating interactions with individuals who have a physical
      disability. DESIGN: In Study 1, participants completed a measure of global self
      esteem and then were randomly assigned to expect either a brief (5 minutes) or
      extended (45 minutes) interaction with a confederate in a wheelchair.
      Participants then completed measures of state affect and meta-evaluations
      (expected evaluations from the partner). Study 2 replicated the design of Study 1
      and additionally randomly assigned participants to be outcome-dependent on the
      partner or not. RESULTS: Study 1 found that individuals reported affective
      experiences and expected meta-evaluations that were consistent with global self
      esteem when expecting a brief interaction but not an extended interaction with
      the partner. Study 2 replicated and extended the results from Study 1,
      demonstrating that self-esteem resumed a priority when participants expected an
      extended interaction that also placed the participant in an outcome-dependent
      role. IMPLICATIONS: Taken together, the results seem to support a dilution of the
      role of self-esteem in simple evaluative situations but not in situations that
      are nonevaluative or situations with combined evaluative factors.

PMID- 21728453
TI  - Both trace and delay conditioned eyeblink responding can be dissociated from
      outcome expectancy.
AB  - Squire and colleagues have proposed that trace and delay eyeblink conditioning
      are fundamentally different kinds of learning: trace conditioning requires
      acquisition of a conscious declarative memory for the stimulus contingencies
      whereas delay conditioning does not. Declarative memory in trace conditioning is
      thought to generate conditioned responding through the activation of a conscious
      expectancy for when the unconditioned stimulus (US) is going to occur. Perruchet
      (1985) has previously shown that in a 50% partial reinforcement design it is
      possible to dissociate single cue delay eyeblink conditioning from conscious
      expectancy for the US by examining performance over runs of reinforced and
      nonreinforced trials. Clark, Manns, and Squire (2001) claim that this
      dissociation does not occur in trace eyeblink conditioning. In the present
      experiment we examined the Perruchet effect for short, moderate, and long trace
      intervals (600, 1000, and 1400 ms) and for the equivalent interstimulus intervals
      (ISIs) in a delay conditioning procedure. We found evidence for a dissociation of
      eyeblink CRs and US expectancy over runs regardless of whether there was a delay
      or a trace arrangement of cues. The reasons for the Perruchet effect are still
      unclear, but the present data suggest that it does not depend on a separate
      nondeclarative system of the type proposed by Squire and colleagues.

PMID- 21728454
TI  - Boosting wisdom: distance from the self enhances wise reasoning, attitudes, and
      behavior.
AB  - Although humans strive to be wise, they often fail to do so when reasoning over
      issues that have profound personal implications. Here we examine whether
      psychological distance enhances wise reasoning, attitudes and behavior under such
      circumstances. Two experiments demonstrate that cueing people to reason about
      personally meaningful issues (Study 1: Career prospects for the unemployed during
      an economic recession; Study 2: Anticipated societal changes associated with
      one's chosen candidate losing the 2008 U.S. Presidential election) from a
      distanced perspective enhances wise reasoning (dialecticism; intellectual
      humility), attitudes (cooperation-related attitude assimilation), and behavior
      (willingness to join a bipartisan group).

PMID- 21728455
TI  - The spatial distribution of attention within and across objects.
AB  - Attention operates to select both spatial locations and perceptual objects.
      However, the specific mechanism by which attention is oriented to objects is not
      well understood. We examined the means by which object structure constrains the
      distribution of spatial attention (i.e., a "grouped array"). Using a modified
      version of the Egly et al. object cuing task, we systematically manipulated
      within-object distance and object boundaries. Four major findings are reported:
      1) spatial attention forms a gradient across the attended object; 2) object
      boundaries limit the distribution of this gradient, with the spread of attention
      constrained by a boundary; 3) boundaries within an object operate similarly to
      across-object boundaries: we observed object-based effects across a discontinuity
      within a single object, without the demand to divide or switch attention between
      discrete object representations; and 4) the gradient of spatial attention across
      an object directly modulates perceptual sensitivity, implicating a relatively
      early locus for the grouped array representation.

PMID- 21728456
TI  - Multiple systems for cognitive control: evidence from a hybrid prime-Simon task.
AB  - Cognitive control resolves conflicts between appropriate and inappropriate
      response tendencies. Is this achieved by a unitary all-purpose conflict control
      system, or do independent subsystems deal with different aspects of conflicting
      information? In a fully factorial hybrid prime-Simon task, participants responded
      to the identity of targets displayed at different nominally irrelevant screen
      locations, preceded by nominally irrelevant, consciously or nonconsciously
      perceived primes. The response required by the target's identity could match or
      mismatch (a) the target's location, and (b) the prime's identity, resulting in
      potential conflict (a) across and (b) within stimulus domains. Conflict effects
      were investigated within and across trials. Results suggest that (i)
      nonconsciously perceived information elicits within-trial control, but--unlike
      consciously perceived information--no across-trial behavioral modulation; (ii)
      separate subsystems deal with conflicts arising from different stimulus domains;
      and (iii) occasional apparent interactions between domains reflect a particular
      difficulty in reactivating a just-discarded response (reactivation aversion
      effect, RAE).

PMID- 21728457
TI  - Frequency-shift detectors bind binaural as well as monaural frequency
      representations.
AB  - Previous psychophysical work provided evidence for the existence of automatic
      frequency-shift detectors (FSDs) that establish perceptual links between
      successive sounds. In this study, we investigated the characteristics of the FSDs
      with respect to the binaural system. Listeners were presented with sound
      sequences consisting of a chord of pure tones followed by a single test tone. Two
      tasks were performed. In the "present/absent" task, the test tone was either
      identical to one of the chord components or positioned halfway in frequency
      between two components, and listeners had to discriminate between these two
      possibilities. In the "up/down" task, the test tone was slightly different in
      frequency from one of the chord components and listeners had to identify the
      direction (up or down) of the corresponding shift. When the test tone was a pure
      tone presented monaurally, either to the same ear as the chord or to the opposite
      ear, listeners performed the up/down task better than the present/absent task.
      This paradoxical advantage for directional frequency shifts, providing evidence
      for FSDs, persisted when the test tone was replaced by a dichotic stimulus
      consisting of noise but evoking a pitch sensation as a consequence of binaural
      processing. Performance in the up/down task was similar for the dichotic stimulus
      and for a monaural narrow-band noise matched in pitch salience to it. Our results
      indicate that the FSDs are insensitive to sound localization mechanisms and
      operate on central frequency representations, at or above the level of
      convergence of the monaural auditory pathways.

PMID- 21728458
TI  - Attention misplaced: the role of diagnostic features in the face-inversion
      effect.
AB  - Inversion disproportionately impairs recognition of face stimuli compared to
      nonface stimuli arguably due to the holistic manner in which faces are processed.
      A qualification is put forward in which the first point fixated on is different
      for upright and inverted faces and this carries some of the face-inversion
      effect. Three experiments explored this possibility by using fixation crosses to
      guide attention to the eye or mouth region of the to-be-presented faces in
      different orientations. Recognition was better when the fixation cross appeared
      at the eye region than at the mouth region. The face-inversion effect was smaller
      when the eyes were cued than when the mouth was cued or when there was no cueing.
      The results suggest that the first facial feature attended to is important for
      accurate face recognition and this may carry some of the effects of inversion.

PMID- 21728460
TI  - Taking a hands-on approach: apparent grasping ability scales the perception of
      object size.
AB  - We examined whether the apparent size of an object is scaled to the morphology of
      the relevant body part with which one intends to act on it. To be specific, we
      tested if the visually perceived size of graspable objects is scaled to the
      extent of apparent grasping ability for the individual. Previous research has
      shown that right-handed individuals perceive their right hand as larger and
      capable of grasping larger objects than their left. In the first 2 experiments,
      we found that objects looked smaller when placed in or judged relative to their
      right hand compared to their left. In the third experiment, we directly
      manipulated apparent hand size by magnifying the participants' hands.
      Participants perceived objects to be smaller when their hand was magnified than
      when their hand was unmagnified. We interpret these results as demonstrating that
      perceivers use the extent of their hands' grasping abilities as "perceptual
      rulers" to scale the apparent size of graspable objects. Furthermore, hand size
      manipulations did not affect the perceived size of objects too big to be grasped,
      which suggests that hand size is only used as a scaling mechanism when the object
      affords the relevant action, in this case, grasping.

PMID- 21728459
TI  - Individual differences in visual word recognition: insights from the English
      Lexicon Project.
AB  - Empirical work and models of visual word recognition have traditionally focused
      on group-level performance. Despite the emphasis on the prototypical reader,
      there is clear evidence that variation in reading skill modulates word
      recognition performance. In the present study, we examined differences among
      individuals who contributed to the English Lexicon Project
      (http://elexicon.wustl.edu), an online behavioral database containing nearly 4
      million word recognition (speeded pronunciation and lexical decision) trials from
      over 1,200 participants. We observed considerable within- and between-session
      reliability across distinct sets of items, in terms of overall mean response time
      (RT), RT distributional characteristics, diffusion model parameters (Ratcliff,
      Gomez, & McKoon, 2004), and sensitivity to underlying lexical dimensions. This
      indicates reliably detectable individual differences in word recognition
      performance. In addition, higher vocabulary knowledge was associated with faster,
      more accurate word recognition performance, attenuated sensitivity to stimuli
      characteristics, and more efficient accumulation of information. Finally, in
      contrast to suggestions in the literature, we did not find evidence that
      individuals were trading-off their utilization of lexical and nonlexical
      information.

PMID- 21728461
TI  - The education of attention as explanation of variability of practice effects:
      learning the final approach phase in a flight simulator.
AB  - The present study reports two experiments in which a total of 20 participants
      without prior flight experience practiced the final approach phase in a fixed
      base simulator. All participants received self-controlled concurrent feedback
      during 180 practice trials. Experiment 1 shows that participants learn more
      quickly under variable practice conditions than under constant practice
      conditions. This finding is attributed to the education of attention to the more
      useful informational variables: Variability of practice reduces the usefulness of
      initially used informational variables, which leads to a quicker change in
      variable use, and hence to a larger improvement in performance. In the practice
      phase of Experiment 2 variability was selectively applied to some experimental
      factors but not to others. Participants tended to converge toward the variables
      that were useful in the specific conditions that they encountered during
      practice. This indicates that an explanation for variability of practice effects
      in terms of the education of attention is a useful alternative to traditional
      explanations based on the notion of the generalized motor program and to
      explanations based on the notions of noise and local minima.

PMID- 21728462
TI  - Modeling the tendency for music to induce movement in humans: first correlations
      with low-level audio descriptors across music genres.
AB  - Groove is often described as the experience of music that makes people tap their
      feet and want to dance. A high degree of consistency in ratings of groove across
      listeners indicates that physical properties of the sound signal contribute to
      groove (Madison, 2006). Here, correlations were assessed between listeners'
      ratings and a number of quantitative descriptors of rhythmic properties for one
      hundred music examples from five distinct traditional music genres. Groove was
      related to several different rhythmic properties, some of which were genre
      specific and some of which were general across genres. Two descriptors
      corresponding to the density of events between beats and the salience of the
      beat, respectively, were strongly correlated with groove across domains. In
      contrast, systematic deviations from strict positions on the metrical grid, so
      called microtiming, did not play any significant role. The results are discussed
      from a functional perspective of rhythmic music to enable and facilitate
      entrainment and precise synchronization among individuals.

PMID- 21728463
TI  - Grouping and emergent features in vision: toward a theory of basic Gestalts.
AB  - Gestalt phenomena are often so powerful that mere demonstrations can confirm
      their existence, but Gestalts have proven hard to define and measure. Here we
      outline a theory of basic Gestalts (TBG) that defines Gestalts as emergent
      features (EFs). The logic relies on discovering wholes that are more
      discriminable than are the parts from which they are built. These wholes contain
      EFs that can act as basic features in human vision. As context is added to a
      visual stimulus, a hierarchy of EFs appears. Starting with a single dot and
      adding a second yields the first two potential EFs: the proximity (distance) and
      orientation (angle) between the two dots. A third dot introduces two more
      potential EFs: symmetry and linearity; a fourth dot produces surroundedness. This
      hierarchy may extend to collinearity, parallelism, closure, and more. We use the
      magnitude of Configural Superiority Effects to measure the salience of EFs on a
      common scale, potentially letting us compare the strengths of various grouping
      principles. TBG appears promising, with our initial experiments establishing and
      quantifying at least three basic EFs in human vision.

PMID- 21728464
TI  - Perceptual load alters visual excitability.
AB  - Increasing perceptual load reduces the processing of visual stimuli outside the
      focus of attention, but the mechanism underlying these effects remains unclear.
      Here we tested an account attributing the effects of perceptual load to
      modulations of visual cortex excitability. In contrast to stimulus competition
      accounts, which propose that load should affect simultaneous, but not sequential,
      stimulus presentations, the visual excitability account makes the novel
      prediction that load should affect detection sensitivity for both simultaneous
      and sequential presentations. Participants fixated a stimulus stream, responding
      to targets defined by either a color (low load) or color and orientation
      conjunctions (high load). Additionally, detection sensitivity was measured for a
      peripheral critical stimulus (CS) presented occasionally. Increasing load at
      fixation reduced sensitivity to the peripheral CSs; this effect was similar
      regardless of whether CSs were presented simultaneously with central stimuli or
      during the (otherwise empty) interval between them. Controls ruled out
      explanations of the results in terms of strategic task prioritization. These
      findings support a cortical excitability account for perceptual load, challenging
      stimulus competition accounts.

PMID- 21728465
TI  - Temporal ventriloquism in a purely temporal context.
AB  - This study examines how audiovisual signals are combined in time for a temporal
      analogue of the ventriloquist effect in a purely temporal context, that is, no
      spatial grounding of signals or other spatial facilitation. Observers were
      presented with two successive intervals, each defined by a 1250-ms tone, and
      indicated in which interval a brief audiovisual stimulus (visual flash + noise
      burst) occurred later. In "test" intervals, the audiovisual stimulus was
      presented with a small asynchrony, while in "probe" intervals it was synchronous
      and presented at various times guided by an adaptive staircase to find the
      perceived temporal location of the asynchronous stimulus. As in spatial
      ventriloquism, and consistent with maximum likelihood estimation (MLE), the
      asynchronous audiovisual signal was shifted toward the more reliably localized
      component (audition, for all observers). Moreover, these temporal shifts could be
      forward or backward in time, depending on the asynchrony order, suggesting
      perceived timing is not entirely determined by physical timing. However, the
      critical signature of MLE combination--better bimodal than unimodal precision-
      was not found. Regardless of the underlying model, these results demonstrate
      temporal ventriloquism in a paradigm that is defined in a purely temporal
      context.

PMID- 21728466
TI  - Conflict adaptation by means of associative learning.
AB  - Cognitive control is responsible for adapting information processing in order to
      carry out tasks more efficiently. Contrasting global versus local control
      accounts, it has recently been proposed that control operates in an associative
      fashion, that is, by binding stimulus-response associations after detection of
      conflict (Verguts & Notebaert, 2009). Here, this prediction is explicitly tested
      for the first time. In a task-switching study where both tasks use the same
      relevant information, we previously reported conflict adaptation over tasks
      (Notebaert & Verguts, 2008). In the current experiment, we demonstrate that this
      is restricted to conditions where both tasks use the same effectors, thereby
      supporting the associative control account.

PMID- 21728467
TI  - Testing probability matching and episodic retrieval accounts of response
      repetition effects in task switching.
AB  - This study takes inventory of available evidence on response repetition (RR)
      effects in task switching, in particular the evidence for RR cost when the task
      switches. The review reveals that relatively few task-switching studies in which
      RR effects were addressed have shown statistical support for RR cost, and that
      almost all are affected by 1 of 2 potential artifacts, either a response bias
      caused by disallowing stimulus repetitions or the effect of including stimulus
      repetitions in data analysis. New results with these factors controlled support
      an episodic retrieval model in which features of the retrieved trace, including
      the stimulus but also the task, task cue, and response, facilitate or interfere
      with performance depending on whether they match or mismatch the current
      processing context.

PMID- 21728468
TI  - Selective attention and distractor frequency in naming performance: comment on
      Dhooge and Hartsuiker (2010).
AB  - E. Dhooge and R. J. Hartsuiker (2010) reported experiments showing that picture
      naming takes longer with low- than high-frequency distractor words, replicating
      M. Miozzo and A. Caramazza (2003). In addition, they showed that this distractor
      frequency effect disappears when distractors are masked or preexposed. These
      findings were taken to refute models like WEAVER++ (A. Roelofs, 2003) in which
      words are selected by competition. However, Dhooge and Hartsuiker do not take
      into account that according to this model, picture-word interference taps not
      only into word production but also into attentional processes. Here, the authors
      indicate that WEAVER++ contains an attentional mechanism that accounts for the
      distractor-frequency effect (A. Roelofs, 2005). Moreover, the authors demonstrate
      that the model accounts for the influence of masking and preexposure, and does so
      in a simpler way than the response exclusion through self-monitoring account
      advanced by Dhooge and Hartsuiker.

PMID- 21728469
TI  - Clarifying the advantage of small samples: as it relates to statistical Wisdom
      and Cahan's (2010) normative intuitions.
AB  - On the basis of earlier findings, we (Fiedler & Kareev, 2006) presented a
      statistical decision model that explains the conditions under which small samples
      of information about choice alternatives inform more correct choices than large
      samples. Such a small-sample advantage (SSA) is predicted for choices, not
      estimations. It is contingent on high constant decision thresholds. The model was
      harshly criticized by Cahan (2010), who argued that the SSA disappears when the
      threshold decreases with increasing sample size and when the costs of incorrect
      decisions are higher than the benefits of correct decisions. We refute Cahan's
      critique, which confuses normative and descriptive arguments. He neither
      questioned our theoretical reasoning nor presented empirical counterevidence.
      Instead, he discarded our model as statistically invalid because the threshold
      does not decrease with increasing sample size. Contrary to this normative
      intuition, which presupposes a significance-testing rationale, we point out that
      decisions are often insensitive to sample size. We also refute Cahan's intuition
      that ignoring the potential asymmetry of gains and losses creates a serious bias
      in favor of the SSA. We regret any misunderstandings resulting from our linking
      the SSA to Bernoulli's law of large numbers.

PMID- 21728470
TI  - An extension to the constructivist coding hypothesis as a learning model for
      selective feedback when the base rate is high.
AB  - Elwin, Juslin, Olsson, and Enkvist (2007) and Henriksson, Elwin, and Juslin
      (2010) offered the constructivist coding hypothesis to describe how people code
      the outcomes of their decisions when availability of feedback is conditional on
      the decision. They provided empirical evidence only for the .5 base rate
      condition. This commentary argues that the constructivist coding hypothesis
      imposes an ever-declining selection rate and overestimates base rate bias for
      high base rate conditions. We provide support based on a simulation model of
      learning under selective feedback with different base rates. Then we discuss
      possible extensions to constructivist coding that can help overcome the problem.

PMID- 21728472
TI  - Exact solution of the nonconsensus opinion model on the line.
AB  - The nonconsensus opinion model (NCO) introduced recently by Shao et al. [Phys.
      Rev. Lett. 103, 018701 (2009)] is solved exactly on the line. Although, as
      expected, the model exhibits no phase transition in one dimension, its study is
      interesting because of the possible connection with invasion percolation with
      trapping. The system evolves exponentially fast to the steady state, rapidly
      developing long-range correlations: The average cluster size in the steady state
      scales as the square of the initial cluster size, of the (uncorrelated) initial
      state. We also discuss briefly the NCO model on Bethe lattices, arguing that its
      phase transition diagram is different than that of regular percolation.

PMID- 21728473
TI  - Solidification along the interface between demixed liquids in monotectic systems.
AB  - The steady-state solidification along the liquid-liquid interface in the
      monotectic system is discussed. A boundary-integral formulation describing the
      diffusion in the two liquid phases is given and the corresponding equations for
      the three interfaces (two solid-liquid interfaces and one liquid-liquid
      interface) are solved. Scaling relations are extracted from the results and
      supported by analytic arguments in the limit of small deviation from the
      monotectic temperature. We present also a complementary phase-field simulation,
      which proves the stability of the process.

PMID- 21728474
TI  - First-order layering and critical wetting transitions in nonadditive hard-sphere
      mixtures.
AB  - Using fundamental-measure density functional theory we investigate entropic
      wetting in an asymmetric binary mixture of hard spheres with positive
      nonadditivity. We consider a general planar hard wall, where preferential
      adsorption is induced by a difference in closest approach of the different
      species and the wall. Close to bulk fluid-fluid coexistence, the phase rich in
      the minority component adsorbs either through a series of first-order layering
      transitions, where an increasing number of liquid layers adsorbs sequentially, or
      via a critical wetting transition, where a thick film grows continuously.

PMID- 21728475
TI  - Aging in glassy polymer-liquid-crystal layers.
AB  - We present in this Rapid Communication experimental evidence of an acceleration
      of the zenithal easy-axis dynamics of a nematic liquid crystal (NLC) with the age
      of a NLC-polymer layer. The comparison with other hard alignment layers strongly
      indicates that the polymer softness and its ability to reorient in the nematic
      ordering field is at the origin of the measured dynamics. The unusual
      acceleration of the dynamics with the polymer age is discussed in terms of this
      unique coupling with the NLC order. The NLC behaves like a physical plasticizer
      as a result of the coupling between the NLC and the polymer orders.

PMID- 21728476
TI  - Free-energy barrier for electric-field-driven polymer entry into nanoscale
      channels.
AB  - Free-energy barrier for entry of a charged polymer into a nanoscale channel by a
      driving electric field is studied theoretically and using molecular dynamics
      simulations. Dependence of the barrier height on the polymer length, the driving
      field strength, and the channel entrance geometry is investigated. Squeezing
      effect of the electric field on the polymer before its entry to the channel is
      taken into account. It is shown that lateral confinement of the polymer prior to
      its entry changes the polymer length dependence of the barrier height noticeably.
      Our theory and simulation results are in good agreement and reasonably describe
      related experimental data.

PMID- 21728477
TI  - Effective free energy for pinned membranes.
AB  - We consider membranes adhered through specific receptor-ligand bonds. Thermal
      undulations of the membrane induce effective interactions between adhesion sites.
      We derive an upper bound to the free energy that is independent of interaction
      details. To the lowest order in a systematic expansion we obtain two-body
      interactions that allow us to map the free energy onto a lattice gas with a
      constant density. The induced interactions alone are not strong enough to lead to
      a condensation of individual adhesion sites. A measure of the thermal roughness
      is shown to depend on the inverse square root of the density of adhesion sites,
      which is in good agreement with previous computer simulations.

PMID- 21728478
TI  - Cooperative crosslink (un)binding in slowly driven bundles of semiflexible
      filaments.
AB  - Combining simulations and theory I study the interplay between bundle elastic
      degrees of freedom and crosslink binding propensity. By slowly driving bundles
      into a deformed configuration, and depending on the mechanical stiffness of the
      crosslinking agent, the binding affinity is shown to display a sudden and
      discontinuous drop. This indicates a cooperative unbinding process that involves
      the crossing of a free-energy barrier. Choosing the proper crosslinker therefore
      not only allows us to change the composite elastic properties of the bundle but
      also the relevant time scales which can be tuned from the single crosslink
      binding rate to the much longer escape time over the free-energy barrier.

PMID- 21728479
TI  - Statistical mechanics of nucleosome ordering by chromatin-structure-induced two
      body interactions.
AB  - One-dimensional arrays of nucleosomes (DNA-bound histone octamers separated by
      stretches of linker DNA) fold into higher-order chromatin structures which
      ultimately make up eukaryotic chromosomes. Chromatin structure formation leads to
      10-11 base pair (bp) discretization of linker lengths caused by the smaller free
      energy cost of packaging nucleosomes into regular chromatin fibers if their
      rotational setting (defined by the DNA helical twist) is conserved. We describe
      nucleosome positions along the fiber using a thermodynamic model of finite-size
      particles with both intrinsic histone-DNA interactions and an effective two-body
      potential. We infer one- and two-body energies directly from high-throughput maps
      of nucleosome positions. We show that higher-order chromatin structure helps
      explains in vitro and in vivo nucleosome ordering in transcribed regions, and
      plays a leading role in establishing well-known 10-11 bp genome-wide periodicity
      of nucleosome positions.

PMID- 21728480
TI  - Viscosity of bacterial suspensions: hydrodynamic interactions and self-induced
      noise.
AB  - The viscosity of a suspension of swimming bacteria is investigated analytically
      and numerically. We propose a simple model that allows for efficient computation
      for a large number of bacteria. Our calculations show that long-range
      hydrodynamic interactions, intrinsic to self-locomoting objects in a viscous
      fluid, result in a dramatic reduction of the effective viscosity. In agreement
      with experiments on suspensions of Bacillus subtilis, we show that the viscosity
      reduction is related to the onset of large-scale collective motion due to
      interactions between the swimmers. The simulations reveal that the viscosity
      reduction occurs only for relatively low concentrations of swimmers: Further
      increases of the concentration yield an increase of the viscosity. We derive an
      explicit asymptotic formula for the effective viscosity in terms of known
      physical parameters and show that hydrodynamic interactions are manifested as
      self-induced noise in the absence of any explicit stochasticity in the system.

PMID- 21728481
TI  - Adaptation reduces variability of the neuronal population code.
AB  - Sequences of events in noise-driven excitable systems with slow variables often
      show serial correlations among their intervals of events. Here, we employ a
      master equation for generalized non-renewal processes to calculate the interval
      and count statistics of superimposed processes governed by a slow adaptation
      variable. For an ensemble of neurons with spike-frequency adaptation, this
      results in the regularization of the population activity and an enhanced
      postsynaptic signal decoding. We confirm our theoretical results in a population
      of cortical neurons recorded in vivo.

PMID- 21728482
TI  - Driving denaturation: nanoscale thermal transport as a probe of DNA melting.
AB  - DNA denaturation has been a subject of intense study due to its relationship to
      DNA transcription and its fundamental importance as a nonlinear structural
      transition. Many aspects of this phenomenon, however, remain poorly understood.
      Existing models fit quite well with experimental results on the fraction of
      unbound base pairs versus temperature, but yield incorrect results for other
      essential quantities such as the base pair fluctuation time scales. Here we
      demonstrate that nanoscale thermal transport can serve as a sensitive probe of
      the underlying microscopic physics responsible for the dynamics of DNA
      denaturation. Specifically, we show that the heat transport properties of DNA are
      altered significantly as it denatures, and this alteration encodes detailed
      information on the dynamics of thermal fluctuations and their interaction along
      the strand. This finding allows for the discrimination between models of DNA
      denaturation and will help shed new light on the nonlinear vibrational dynamics
      of this important molecule.

PMID- 21728483
TI  - Ethanol enhances collective dynamics of lipid membranes.
AB  - From inelastic neutron-scattering experiments and all atom molecular dynamics
      simulations we present evidence for a low-energy dynamical mode in the fluid
      phase of a 1,2-dimyristoyl-sn-glycero-3-phoshatidylcholine (DMPC) bilayer
      immersed in a 5% water/ethanol solution. In addition to the well-known phonon
      that shows a liquidlike dispersion with energies up to 4.5 meV, we observe an
      additional mode at smaller energies of 0.8 meV, which shows little or no
      dispersion. Both modes show transverse properties and might be related to
      molecular motion perpendicular to the bilayer.

PMID- 21728484
TI  - Aspect-ratio dependence of thermodynamic Casimir forces.
AB  - We consider the three-dimensional Ising model in a L(?)*L(?)*L(?) cuboid geometry
      with a finite aspect ratio rho=L(?)/L(?) and periodic boundary conditions along
      all directions. For this model the finite-size scaling functions of the excess
      free energy and thermodynamic Casimir force are evaluated numerically by means of
      Monte Carlo simulations. The Monte Carlo results compare well with recent field
      theoretical results for the Ising universality class at temperatures above and
      slightly below the bulk critical temperature T(c). Furthermore, the excess free
      energy and Casimir force scaling functions of the two-dimensional Ising model are
      calculated exactly for arbitrary rho and compared to the three-dimensional case.
      We give a general argument that the Casimir force vanishes at the critical point
      for rho=1 and becomes repulsive in periodic systems for rho>1.

PMID- 21728485
TI  - Experimental evidence of the role of compound counting processes in random walk
      approaches to fractional dynamics.
AB  - We present dielectric spectroscopy data obtained for gallium-doped
      Cd(0.99)Mn(0.01)Te:Ga mixed crystals, which exhibit a very special case of the
      two-power-law relaxation pattern with the high-frequency power-law exponent equal
      to 1. We explain this behavior, which cannot be fitted by any of the well-known
      empirical relaxation functions, in a subordinated diffusive framework. We propose
      a diffusion scenario based on a renormalized clustering of a random number of
      spatio-temporal steps in the continuous-time random walk. Such a construction
      substitutes the renewal counting process, which is used in the classical
      continuous time random walk methodology, with a compound counting one. As a
      result, we obtain an appropriate relaxation function governing the observed
      nonstandard pattern, and we show the importance of the compound counting
      processes in studying fractional dynamics of complex systems.

PMID- 21728486
TI  - Real-space renormalization group for the transverse-field Ising model in two and
      three dimensions.
AB  - The two- and three-dimensional transverse-field Ising models with ferromagnetic
      exchange interactions are analyzed by means of the real-space renormalization
      group method. The basic strategy is a generalization of a method developed for
      the one-dimensional case, which exploits the exact invariance of the model under
      renormalization and is known to give the exact values of the critical point and
      critical exponent nu. The resulting values of the critical exponent nu in two and
      three dimensions are in good agreement with those for the classical Ising model
      in three and four dimensions. To the best of our knowledge, this is the first
      example in which a real-space renormalization group on (2+1)- and (3+1)
      dimensional Bravais lattices yields accurate estimates of the critical exponents.

PMID- 21728487
TI  - Zero-temperature relaxation of three-dimensional Ising ferromagnets.
AB  - We investigate the properties of the Ising-Glauber model on a periodic cubic
      lattice of linear dimension L after a quench to zero temperature. The resulting
      evolution is extremely slow, with long periods of wandering on constant energy
      plateaus, punctuated by occasional energy-decreasing spin-flip events. The
      characteristic time scale tau for this relaxation grows exponentially with the
      system size; we provide a heuristic and numerical evidence that tau~exp(L(2)).
      For all but the smallest-size systems, the long-time state is almost never
      static. Instead, the system contains a small number of "blinker" spins that
      continue to flip forever with no energy cost. Thus, the system wanders ad
      infinitum on a connected set of equal-energy blinker states. These states are
      composed of two topologically complex interwoven domains of opposite phases. The
      average genus g(L) of the domains scales as L(gamma), with gamma~1.7; thus,
      domains typically have many holes, leading to a "plumber's nightmare" geometry.

PMID- 21728488
TI  - Swarms with canonical active Brownian motion.
AB  - We present a swarm model of Brownian particles with harmonic interactions, where
      the individuals undergo canonical active Brownian motion, i.e., each Brownian
      particle can convert internal energy to mechanical energy of motion. We assume
      the existence of a single global internal energy of the system. Numerical
      simulations show amorphous swarming behavior as well as static configurations.
      Analytic understanding of the system is provided by studying stability properties
      of equilibria.

PMID- 21728489
TI  - Particle diode: rectification of interacting Brownian ratchets.
AB  - Transport of Brownian particles interacting with each other via the Morse
      potential is investigated in the presence of an ac driving force applied locally
      at one end of the chain. By using numerical simulations, we find that the system
      can behave as a particle diode for both overdamped and underdamped cases. For low
      frequencies, the transport from the free end to the ac acting end is prohibited,
      while the transport from the ac acting end to the free end is permitted. However,
      the polarity of the particle diode will reverse for medium frequencies. There
      exists an optimal value of the well depth of the interaction potential at which
      the average velocity takes its maximum. The average velocity upsilon decreases
      monotonically with the system size N by a power law upsilon ? N(-1).

PMID- 21728490
TI  - Slow relaxation and aging kinetics for the driven lattice gas.
AB  - We numerically investigate the long-time behavior of the density-density
      autocorrelation function in driven lattice gases with particle exclusion and
      periodic boundary conditions in one, two, and three dimensions using precise
      Monte Carlo simulations. In the one-dimensional asymmetric exclusion process on a
      ring with half the lattice sites occupied, we find that correlations induce
      extremely slow relaxation to the asymptotic power law decay. We compare the
      crossover functions obtained from our simulations with various analytic results
      in the literature and analyze the characteristic oscillations that occur in
      finite systems away from half-filling. As expected, in three dimensions
      correlations are weak and consequently the mean-field description is adequate. We
      also investigate the relaxation toward the nonequilibrium steady state in the two
      time density-density autocorrelations, starting from strongly correlated initial
      conditions. We obtain simple aging scaling behavior in one, two, and three
      dimensions, with the expected power laws.

PMID- 21728491
TI  - Saddles, arrows, and spirals: deterministic trajectories in cyclic competition of
      four species.
AB  - Population dynamics in systems composed of cyclically competing species has been
      of increasing interest recently. Here we investigate a system with four or more
      species. Using mean field theory, we study in detail the trajectories in
      configuration space of the population fractions. We discover a variety of orbits,
      shaped like saddles, spirals, and straight lines. Many of their properties are
      found explicitly. Most remarkably, we identify a collective variable that evolves
      simply as an exponential: Q ? e(lambdat), where lambda is a function of the
      reaction rates. It provides information on the state of the system for late times
      (as well as for t->-infinity). We discuss implications of these results for the
      evolution of a finite, stochastic system. A generalization to an arbitrary number
      of cyclically competing species yields valuable insights into universal
      properties of such systems.

PMID- 21728492
TI  - Record statistics for biased random walks, with an application to financial data.
AB  - We consider the occurrence of record-breaking events in random walks with
      asymmetric jump distributions. The statistics of records in symmetric random
      walks was previously analyzed by Majumdar and Ziff [Phys. Rev. Lett. 101, 050601
      (2008)] and is well understood. Unlike the case of symmetric jump distributions,
      in the asymmetric case the statistics of records depends on the choice of the
      jump distribution. We compute the record rate P(n)(c), defined as the probability
      for the nth value to be larger than all previous values, for a Gaussian jump
      distribution with standard deviation sigma that is shifted by a constant drift c.
      For small drift, in the sense of c/sigma ? n(-1/2), the correction to P(n)(c)
      grows proportional to arctan(?n) and saturates at the value c/(?2)sigma. For
      large n the record rate approaches a constant, which is approximately given by 1
      (sigma/?(2pi)c)exp(-c(2)/2sigma(2)) for c/sigma ? 1. These asymptotic results
      carry over to other continuous jump distributions with finite variance. As an
      application, we compare our analytical results to the record statistics of 366
      daily stock prices from the Standard & Poor's 500 index. The biased random walk
      accounts quantitatively for the increase in the number of upper records due to
      the overall trend in the stock prices, and after detrending the number of upper
      records is in good agreement with the symmetric random walk. However the number
      of lower records in the detrended data is significantly reduced by a mechanism
      that remains to be identified.

PMID- 21728493
TI  - Universal features of the free-energy functional at the freezing transition for
      repulsive potentials.
AB  - The free-energy difference between coexisting solid and liquid phases is studied
      in the context of classical density functional theory (DFT). A bridge function is
      used to represent the higher-order (n>2) terms in the perturbative expansion of
      the excess Helmholtz free energy, and the values of this bridge function within
      the solid lattice are determined by inversion using literature Monte Carlo
      simulation results. Four potential models, specifically hard-sphere and inverse
      twelfth-, sixth-, and fourth-power repulsive, are studied. The face-centered
      cubic (fcc) solid is considered for the hard-sphere and inverse twelfth- and
      sixth-power potentials, while the body-centered cubic (bcc) solid is considered
      for the inverse sixth- and fourth-power potentials. For a given solid structure
      there is a remarkable similarity among the bridge functions for different
      potentials that is analogous to the universality in the sum of elementary
      diagrams, or bridge functions, of liquid-state theory as originally observed by
      Rosenfeld and Ashcroft [Phys. Rev. A 20, 1208 (1979)]. In further analogy with
      liquid-state theory, the bridge functions in the present problem are plotted as
      functionals of the second-order convolution term in the perturbative expansion.
      In each case, the plot indicates a unique functionality in the dense regions of
      the solid near the lattice sites but a scattered and nonunique behavior in the
      void regions. Interestingly, knowledge of the functional relationship in the
      unique region near the lattice sites seems to be sufficient to quantitatively
      model the solid-fluid phase transition. These qualitative observations are true
      for both fcc and bcc solid phases, although there are some quantitative
      differences between them. The findings suggest that pursuit of a closure-based
      DFT of solid-fluid transitions may be profitable.

PMID- 21728494
TI  - Out-of-equilibrium phase transitions in the Hamiltonian mean-field model: a
      closer look.
AB  - We provide a detailed discussion of out-of-equilibrium phase transitions in the
      Hamiltonian mean-field (HMF) model in the framework of Lynden-Bell's statistical
      theory of the Vlasov equation. For two-level initial conditions, the caloric
      curve beta(E) only depends on the initial value f(0) of the distribution
      function. We evidence different regions in the parameter space where the nature
      of the phase transitions between magnetized and nonmagnetized states changes: (i)
      For f(0)>0.10965, the system displays a second-order phase transition; (ii) for
      0.109497<f(0)<0.10965, the system displays a second-order phase transition and a
      first-order phase transition; (iii) for 0.10947<f(0)<0.109497, the system
      displays two second-order phase transitions; and (iv) for f(0)<0.1047, there is
      no phase transition. The passage from a first-order to a second-order phase
      transition corresponds to a tricritical point. The sudden appearance of two
      second-order phase transitions from nothing corresponds to a second-order
      azeotropy. This is associated with a phenomenon of phase reentrance. When
      metastable states are taken into account, the problem becomes even richer. In
      particular, we find another situation of phase reentrance. We consider both
      microcanonical and canonical ensembles and report the existence of a tiny region
      of ensemble inequivalence. We also explain why the use of the initial
      magnetization M(0) as an external parameter, instead of the phase level f(0), may
      lead to inconsistencies in the thermodynamical analysis. Finally, we mention
      different causes of incomplete relaxation that could be a limitation to the
      application of Lynden-Bell's theory.

PMID- 21728495
TI  - Information-based detection of nonlinear Granger causality in multivariate
      processes via a nonuniform embedding technique.
AB  - We present an approach, framed in information theory, to assess nonlinear
      causality between the subsystems of a whole stochastic or deterministic dynamical
      system. The approach follows a sequential procedure for nonuniform embedding of
      multivariate time series, whereby embedding vectors are built progressively on
      the basis of a minimization criterion applied to the entropy of the present state
      of the system conditioned to its past states. A corrected conditional entropy
      estimator compensating for the biasing effect of single points in the quantized
      hyperspace is used to guarantee the existence of a minimum entropy rate at which
      to terminate the procedure. The causal coupling is detected according to the
      Granger notion of predictability improvement, and is quantified in terms of
      information transfer. We apply the approach to simulations of deterministic and
      stochastic systems, showing its superiority over standard uniform embedding.
      Effects of quantization, data length, and noise contamination are investigated.
      As practical applications, we consider the assessment of cardiovascular
      regulatory mechanisms from the analysis of heart period, arterial pressure, and
      respiration time series, and the investigation of the information flow across
      brain areas from multichannel scalp electroencephalographic recordings.

PMID- 21728496
TI  - Boundary conditions of normal and anomalous diffusion from thermal equilibrium.
AB  - Infiltration of diffusing particles from one material to another, where the
      diffusion mechanism is either normal or anomalous, is a widely observed
      phenomenon. Starting with an underlying continuous-time random-walk model, we
      derive the boundary conditions for the diffusion equations describing this
      problem. We discuss a simple method showing how the boundary conditions can be
      determined from equilibrium experiments. When the diffusion processes are close
      to thermal equilibrium, the boundary conditions are determined by a thermal
      Boltzmann factor, which in turn controls the solution of the problem.

PMID- 21728497
TI  - Quantum heat transfer: a Born-Oppenheimer method.
AB  - We develop a Born-Oppenheimer-type formalism for the description of quantum
      thermal transport across hybrid nanoscale objects. Our formalism is suitable for
      treating heat transfer in the off-resonant regime, where, e.g., the relevant
      vibrational modes of the interlocated molecule are high relative to typical bath
      frequencies, and at low temperatures when tunneling effects dominate. A general
      expression for the thermal energy current is accomplished in the form of a
      generalized Landauer formula. In the harmonic limit this expression reduces to
      the standard Landauer result for heat transfer. In the presence of
      nonlinearities, multiphonon effects are realized.

PMID- 21728498
TI  - First-passage and first-exit times of a Bessel-like stochastic process.
AB  - We study a stochastic process X(t) which is a particular case of the Rayleigh
      process and whose square is the Bessel process, with various applications in
      physics, chemistry, biology, economics, finance, and other fields. The stochastic
      differential equation is dX(t)=(nD/X(t))dt+?(2D)dW(t), where W(t) is the Wiener
      process. The drift term can arise from a logarithmic potential or from taking
      X(t) as the norm of a multidimensional random walk. Due to the singularity of the
      drift term for X(t)=0, different natures of boundary at the origin arise
      depending on the real parameter n: entrance, exit, and regular. For each of them
      we calculate analytically and numerically the probability density functions of
      first-passage times or first-exit times. Nontrivial behavior is observed in the
      case of a regular boundary.

PMID- 21728499
TI  - Universality classes of first-passage-time distribution in confined media.
AB  - We study the first-passage time (FPT) distribution to a target site for a random
      walker evolving in a bounded domain. We show that in the limit of large volume of
      the confining domain, this distribution falls into universality classes indexed
      by the walk dimension d(w) and the fractal dimension d(f) of the medium, which
      have been recently identified previously [Benichou et al., Nat. Chem. 2, 472
      (2010)]. We present in this paper a complete derivation of these universal
      distributions, discuss extensively the range of applicability of the results, and
      extend the method to continuous-time random walks. This analysis puts forward the
      importance of the geometry, and in particular the position of the starting point,
      in first-passage statistics. Analytical results are validated by numerical
      simulations, applied to various models of transport in disordered media, which
      illustrate the universality classes of the FPT distribution.

PMID- 21728500
TI  - Indirect control of transport and interaction-induced negative mobility in an
      overdamped system of two coupled particles.
AB  - One-dimensional transport of an overdamped Brownian particle biased by an
      external constant force does not exhibit negative mobility. However, when the
      particle is coupled to another particle, negative mobility can arise. We present
      a minimal model and propose a scenario in which only one (say, the first)
      particle is dc biased by a constant force and ac driven by an unbiased harmonic
      signal. In this way we intend to achieve two aims at once: (i) negative mobility
      of the first particle, which is exclusively induced by coupling to the second
      particle and (ii) indirect control of the transport properties of the second
      particle by manipulating the first particle only. For instance, the sign and
      amplitude of the averaged stationary velocity of the second particle can be
      steered by the driving applied to the first particle. As an experimentally
      realizable system, we propose two coupled resistively shunted Josephson
      junctions.

PMID- 21728501
TI  - Nonequilibrium transport on a quantum molecular chain in terms of the complex
      Liouvillian spectrum.
AB  - The transport process in a molecular chain in a nonequilibrium stationary state
      is theoretically investigated. The molecule is interacting at both ends with
      thermal baths of different temperatures, while no dissipation mechanism is
      contained inside the molecular chain. We have first obtained the nonequilibrium
      stationary state outside the Hilbert space in terms of the complex spectral
      representation of Liouvillian. The nonequilibrium stationary state is obtained as
      an eigenstate of the Liouvillian, which is constructed through the collision
      invariant of the kinetic equation. The eigenstate of the Liouvillian contains
      information on the spatial correlation between the molecular chain and the
      thermal baths. While energy flow in the nonequilibrium state which is due to the
      first-order correlation can be described by the Landauer formula, the particle
      current due to the second-order correlation cannot be described by the Landauer
      formula. The present method provides a simple way to evaluate the energy
      transport in a molecular chain in a nonequilibrium situation.

PMID- 21728502
TI  - Random sequential adsorption of polyatomic species on fractal substrates.
AB  - Random sequential adsorption of k-mers of different sizes and shapes deposited on
      two types of fractal surfaces (deterministic and statistical) is studied. These
      kinds of substrates present intrinsic heterogeneities. As a consequence, the
      average coordination number depends on the topology that characterizes the
      adsorbent. For discrete models, at the late stage the surface coverage evolves
      according to theta(t)=theta(j)-Aexp[-t/sigma], where theta(j) is the jamming
      coverage while A and sigma are fitting parameters. A detailed analysis of how
      these main quantities [theta(j), sigma] depend on the relationship between the
      geometry of the adsorbate and the adsorbent is presented. The results obtained
      suggest that the symmetry of the substrate may exert a decisive influence on the
      adsorption kinetics of polyatomic species.

PMID- 21728503
TI  - Brownian motor with competing spatial and temporal asymmetry of potential energy.
AB  - A Brownian motor is considered which operates due to asymmetric dichotomic
      fluctuations of the spatially periodic asymmetric potential energy. As shown, the
      motion direction and stopping points of this motor are dictated by the
      competition between the spatial and temporal asymmetry of the potential energy
      (or solely by temporal asymmetry in the case that the potential energy sign
      fluctuates). For an asymmetric sawtooth potential, the Brownian-particle average
      velocity is calculated numerically as a function of certain parameters of the
      model, whereas the low-frequency and low-energy approximations allow the
      corresponding analytical relationships to be derived for an arbitrarily shaped
      potential profile. It is shown that temporal asymmetry is not necessary for
      stopping point occurrence provided that the potential profile fluctuates not only
      in amplitude but in shape as well. This inference is illustrated by photoinduced
      fluctuations of the potential energy for a number of substituted arylpyrene
      molecules on a substrate with symmetrically distributed charge density.

PMID- 21728504
TI  - Boundary effect correction in k-nearest-neighbor estimation.
AB  - The problem of the boundary effect for the k-nearest-neighbor (kNN) estimation is
      addressed, and a correction method is suggested. The correction is proposed for
      bounded distributions, but it can be used for any set of bounded samples. We
      apply the proposed correction to entropy estimation of multidimensional
      distributions and time series, and this correction reduces considerably the bias
      and statistical errors in the estimation. For a small sample size or high
      dimensional data, the corrected estimator outperforms the uncorrected estimator
      significantly. This advantage makes the kNN method applicable to more real-life
      situations, e.g., the analysis of biological and molecular data.

PMID- 21728505
TI  - Momentary information transfer as a coupling measure of time series.
AB  - We propose a method to analyze couplings between two simultaneously measured time
      series. Our approach is based on conditional mutual sorting information. It is
      related to other concepts for detecting coupling directions: the old idea of
      Marko for directed information and the more recent concept of Schreiber's
      transfer entropy. By setting suitable conditions we first of all consider
      momentary information in both time series. This enables the detection not only of
      coupling directions but also delays. Sorting information refers to ordinal
      properties of time series, which makes the analysis robust with respect to
      strictly monotonous distortions and thus very useful in the analysis of proxy
      data in climatology. Fortunately, ordinal analysis is easy and fast to compute.
      We consider also the problem of reliable estimation from finite time series.

PMID- 21728506
TI  - High-dimensional inference with the generalized Hopfield model: principal
      component analysis and corrections.
AB  - We consider the problem of inferring the interactions between a set of N binary
      variables from the knowledge of their frequencies and pairwise correlations. The
      inference framework is based on the Hopfield model, a special case of the Ising
      model where the interaction matrix is defined through a set of patterns in the
      variable space, and is of rank much smaller than N. We show that maximum
      likelihood inference is deeply related to principal component analysis when the
      amplitude of the pattern components xi is negligible compared to ?N. Using
      techniques from statistical mechanics, we calculate the corrections to the
      patterns to the first order in xi/?N. We stress the need to generalize the
      Hopfield model and include both attractive and repulsive patterns in order to
      correctly infer networks with sparse and strong interactions. We present a simple
      geometrical criterion to decide how many attractive and repulsive patterns should
      be considered as a function of the sampling noise. We moreover discuss how many
      sampled configurations are required for a good inference, as a function of the
      system size N and of the amplitude xi. The inference approach is illustrated on
      synthetic and biological data.

PMID- 21728507
TI  - Ballistic, diffusive, and localized transport in surface-disordered systems: two
      mode waveguide.
AB  - This paper presents an analytical study of the coexistence of different transport
      regimes in quasi-one-dimensional surface-disordered waveguides (or electron
      conductors). To elucidate main features of surface scattering, the case of two
      open modes (channels) is considered in great detail. Main attention is paid to
      the transmission in dependence on various parameters of the model with two types
      of rough-surface profiles (symmetric and antisymmetric). It is shown that
      depending on the symmetry, basic mechanisms of scattering can be either enhanced
      or suppressed. As a consequence, different transport regimes can be realized.
      Specifically, in the two-mode waveguide with symmetric rough boundaries, there
      are ballistic, localized and coexistence transport regimes. In the waveguide with
      antisymmetric roughness of lateral walls, another regime of the diffusive
      transport can arise. Our study allows to reveal the interplay between all
      relevant scattering mechanisms, in particular, the role of the so-called square
      gradient scattering which is typically neglected in literature, however, can give
      a strong impact to the transmission.

PMID- 21728508
TI  - Statistical mechanics of structural and temporal credit assignment effects on
      learning in neural networks.
AB  - Neural networks can learn flexible input-output associations by changing their
      synaptic weights. The representational performance and learning dynamics of
      neural networks are intensively studied in several fields. Neural networks face
      the "credit assignment problem" in situations in which only incomplete
      performance evaluations are available. The credit assignment problem is that a
      network should assign credit or blame for its behaviors according to the
      contribution to the network performance. In reinforcement learning, a scalar
      evaluation signal is delivered to a network. The two main types of credit
      assignment problems in reinforcement learning are structural and temporal, that
      is, which parameters of the network (structural) and which past network
      activities (temporal) are related to an evaluation signal given from an
      environment. In this study, we apply statistical mechanical analysis to the
      learning processes in a simple neural network model to clarify the effects of two
      kinds of credit assignments and their interactions. Our model is based on node
      perturbation learning with eligibility trace. Node perturbation is a stochastic
      gradient learning method that can solve structural credit assignment problems by
      introducing a perturbation into the system output. The eligibility trace
      preserves the past network activities with a temporal credit to deal with the
      delay of an instruction signal. We show that both credit assignment effects
      mutually interact and the optimal time constant of the eligibility trace varies
      not only for the evaluation delay but also the network size.

PMID- 21728509
TI  - Collapse transition of randomly branched polymers: renormalized field theory.
AB  - We present a minimal dynamical model for randomly branched isotropic polymers,
      and we study this model in the framework of renormalized field theory. For the
      swollen phase, we show that our model provides a route to understand the well
      established dimensional-reduction results from a different angle. For the
      collapse theta transition, we uncover a hidden Becchi-Rouet-Stora supersymmetry,
      signaling the sole relevance of tree configurations. We correct the long-standing
      one-loop results for the critical exponents, and we push these results on to two
      loop order. For the collapse theta' transition, we find a runaway of the
      renormalization group flow, which lends credence to the possibility that this
      transition is a fluctuation-induced first-order transition. Our dynamical model
      allows us to calculate for the first time the fractal dimension of the shortest
      path on randomly branched polymers in the swollen phase as well as at the
      collapse transition and related fractal dimensions.

PMID- 21728510
TI  - Percolation in networks composed of connectivity and dependency links.
AB  - Networks composed from both connectivity and dependency links were found to be
      more vulnerable compared to classical networks with only connectivity links.
      Their percolation transition is usually of a first order compared to the second
      order transition found in classical networks. We analytically analyze the effect
      of different distributions of dependencies links on the robustness of networks.
      For a random Erdos-Renyi (ER) network with average degree k that is divided into
      dependency clusters of size s, the fraction of nodes that belong to the giant
      component P(infinity) is given by P(infinity)=p(s-1)[1-exp(-kpP(infinity))](s),
      where 1-p is the initial fraction of removed nodes. Our general result coincides
      with the known Erdos-Renyi equation for random networks for s=1. For networks
      with Poissonian distribution of dependency links we find that P(infinity) is
      given by P(infinity)=f(k,p)(P(infinity))e(([s]-1)[pf(k,p)(P(infinity))-1]), where
      f(k,p)(P(infinity))=1-exp(-kpP(infinity)) and [s] is the mean value of the size
      of dependency clusters. For networks with Gaussian distribution of dependency
      links we show how the average and width of the distribution affect the robustness
      of the networks.

PMID- 21728511
TI  - Dynamical analysis of the exclusive queueing process.
AB  - Recently, the stationary state of a parallel-update totally asymmetric simple
      exclusion process with varying system length, which can be regarded as a queueing
      process with excluded-volume effect (exclusive queueing process), was obtained [C
      Arita and D Yanagisawa, J. Stat. Phys. 141, 829 (2010)]. In this paper, we
      analyze the dynamical properties of the number of particles [N(t)] and the
      position of the last particle (the system length) [L(t)], using an analytical
      method (generating function technique) as well as a phenomenological description
      based on domain-wall dynamics and Monte Carlo simulations. The system exhibits
      two phases corresponding to linear convergence or divergence of [N(t)] and
      [L(t)]. These phases can both further be subdivided into high-density and maximal
      current subphases. The predictions of the domain-wall theory are found to be in
      very good agreement quantitively with results from Monte Carlo simulations in the
      convergent phase. On the other hand, in the divergent phase, only the prediction
      for [N(t)] agrees with simulations.

PMID- 21728512
TI  - Self-organized criticality as Witten-type topological field theory with
      spontaneously broken Becchi-Rouet-Stora-Tyutin symmetry.
AB  - Here, a scenario is proposed, according to which a generic self-organized
      critical (SOC) system can be looked upon as a Witten-type topological field
      theory (W-TFT) with spontaneously broken Becchi-Rouet-Stora-Tyutin (BRST)
      symmetry. One of the conditions for the SOC is the slow driving noise, which
      unambiguously suggests Stratonovich interpretation of the corresponding
      stochastic differential equation (SDE). This, in turn, necessitates the use of
      Parisi-Sourlas-Wu stochastic quantization procedure, which straightforwardly
      leads to a model with BRST-exact action, i.e., to a W-TFT. In the parameter space
      of the SDE, there must exist full-dimensional regions where the BRST symmetry is
      spontaneously broken by instantons, which in the context of SOC are essentially
      avalanches. In these regions, the avalanche-type SOC dynamics is liberated from
      overwise a rightful dynamics-less W-TFT, and a Goldstone mode of Fadeev-Popov
      ghosts exists. Goldstinos represent moduli of instantons (avalanches) and being
      gapless are responsible for the critical avalanche distribution in the low
      energy, long-wavelength limit. The above arguments are robust against moderate
      variations of the SDE's parameters and the criticality is "self-tuned." The
      proposition of this paper suggests that the machinery of W-TFTs may find its
      applications in many different areas of modern science studying various physical
      realizations of SOC. It also suggests that there may in principle exist a
      connection between some SOC's and the concept of topological quantum computing.

PMID- 21728513
TI  - Transmission of information between complex systems: 1/f resonance.
AB  - We study the transport of information between two complex systems with similar
      properties. Both systems generate non-Poisson renewal fluctuations with a power
      law spectrum 1/f(3-MU), the case MU=2 corresponding to ideal 1/f noise. We denote
      by MU(S) and MU(P) the power-law indexes of the system of interest S and the
      perturbing system P, respectively. By adopting a generalized fluctuation
      dissipation theorem (FDT) we show that the ideal condition of 1/f noise for both
      systems corresponds to maximal information transport. We prove that to make the
      system S respond when MU(S)<2 we have to set the condition MU(P)<2. In the latter
      case, if MU(P)<MU(S), the system S inherits the relaxation properties of the
      perturbing system. In the case where MU(P)>2, no response and no information
      transmission occurs in the long-time limit. We consider two possible
      generalizations of the fluctuation dissipation theorem and show that both lead to
      maximal information transport in the condition of 1/f noise.

PMID- 21728514
TI  - Three-phase coexistence with sequence partitioning in symmetric random block
      copolymers.
AB  - We inquire into the possible coexistence of macroscopic and microstructured
      phases in random Q-block copolymers built of incompatible monomer types A and B
      with equal average concentrations. In our microscopic model, one block comprises
      M identical monomers. The block-type sequence distribution is Markovian and
      characterized by the correlation lambda. Upon increasing the incompatibility chi
      (by decreasing temperature) in the disordered state, the known ordered phases
      form: for lambda>lambda(c), two coexisting macroscopic A- and B-rich phases, for
      lambda<lambda(c), a microstructured (lamellar) phase with wave number k(lambda).
      In addition, we find a fourth region in the lambda-chi plane where these three
      phases coexist, with different, non-Markovian sequence distributions
      (fractionation). Fractionation is revealed by our analytically derived multiphase
      free energy, which explicitly accounts for the exchange of individual sequences
      between the coexisting phases. The three-phase region is reached, either from the
      macroscopic phases, via a third lamellar phase that is rich in alternating
      sequences, or, starting from the lamellar state, via two additional homogeneous,
      homopolymer-enriched phases. These incipient phases emerge with zero volume
      fraction. The four regions of the phase diagram meet in a multicritical point
      (lambda(c),chi(c)), at which A-B segregation vanishes. The analytical method,
      which for the lamellar phase assumes weak segregation, thus proves reliable
      particularly in the vicinity of (lambda(c),chi(c)). For random triblock
      copolymers, Q=3, we find the character of this point and the critical exponents
      to change substantially with the number M of monomers per block. The results for
      Q=3 in the continuous-chain limit M->infinity are compared to numerical self
      consistent field theory (SCFT), which is accurate at larger segregation.

PMID- 21728515
TI  - Condensate fluctuations of interacting Bose gases within a microcanonical
      ensemble.
AB  - Based on counting statistics and Bogoliubov theory, we present a recurrence
      relation for the microcanonical partition function for a weakly interacting Bose
      gas with a finite number of particles in a cubic box. According to this
      microcanonical partition function, we calculate numerically the distribution
      function, condensate fraction, and condensate fluctuations for a finite and
      isolated Bose-Einstein condensate. For ideal and weakly interacting Bose gases,
      we compare the condensate fluctuations with those in the canonical ensemble. The
      present approach yields an accurate account of the condensate fluctuations for
      temperatures close to the critical region. We emphasize that the interactions
      between excited atoms turn out to be important for moderate temperatures.

PMID- 21728516
TI  - Anomalous local coordination, density fluctuations, and void statistics in
      disordered hyperuniform many-particle ground states.
AB  - We provide numerical constructions of one-dimensional hyperuniform many-particle
      distributions that exhibit unusual clustering and asymptotic local number density
      fluctuations growing more slowly than the volume of an observation window but
      faster than the surface area. Hyperuniformity, defined by vanishing infinite
      wavelength local density fluctuations, provides a quantitative metric of global
      order within a many-particle configuration and signals the onset of an "inverted"
      critical point in which the direct correlation function becomes long ranged. By
      targeting a specified form of the structure factor at small wavenumbers
      (S(k)~k(alpha) for 0<alpha<1) using collective density variables, we are able to
      tailor the form of asymptotic local density fluctuations while simultaneously
      measuring the effect of imposing weak and strong constraints on the available
      degrees of freedom within the system. This procedure is equivalent to finding the
      (possibly disordered) classical ground state of an interacting many-particle
      system with up to four-body interactions. Even in one dimension, the long-range
      effective interactions induce clustering and nontrivial phase transitions in the
      resulting ground-state configurations. We provide an analytical connection
      between the fraction of constrained degrees of freedom within the system and the
      disorder-order phase transition for a class of target structure factors by
      examining the realizability of the constrained contribution to the pair
      correlation function. Our results explicitly demonstrate that disordered
      hyperuniform many-particle ground states, and therefore also point distributions,
      with substantial clustering can be constructed. We directly relate the local
      coordination structure of our point patterns to the distribution of the void
      space external to the particles, and we provide a scaling argument for the
      configurational entropy (analogous to spin-frustated system) of the disordered
      ground states. By emphasizing the intimate connection between geometrical
      constraints on the particle distribution and structural regularity, our work has
      direct implications for higher-dimensional systems, including an understanding of
      the appearance of hyperuniformity and quasi-long-range pair correlations in
      maximally random strictly jammed packings of hard spheres.

PMID- 21728517
TI  - Heterogeneous k-core versus bootstrap percolation on complex networks.
AB  - We introduce the heterogeneous k-core, which generalizes the k-core, and contrast
      it with bootstrap percolation. Vertices have a threshold r(i), that may be
      different at each vertex. If a vertex has fewer than r(i) neighbors it is pruned
      from the network. The heterogeneous k-core is the subgraph remaining after no
      further vertices can be pruned. If the thresholds r(i) are 1 with probability f,
      or k >= 3 with probability 1-f, the process can be thought of as a pruning
      process counterpart to ordinary bootstrap percolation, which is an activation
      process. We show that there are two types of transitions in this heterogeneous k
      core process: the giant heterogeneous k-core may appear with a continuous
      transition and there may be a second discontinuous hybrid transition. We compare
      critical phenomena, critical clusters, and avalanches at the heterogeneous k-core
      and bootstrap percolation transitions. We also show that the network structure
      has a crucial effect on these processes, with the giant heterogeneous k-core
      appearing immediately at a finite value for any f>0 when the degree distribution
      tends to a power law P(q)~q(-gamma) with gamma<3.

PMID- 21728518
TI  - Entropic particle transport: higher-order corrections to the Fick-Jacobs
      diffusion equation.
AB  - Transport of point-size Brownian particles under the influence of a constant and
      uniform force field through a planar three-dimensional channel with smoothly
      varying, axis-symmetric periodic side walls is investigated. Here we employ an
      asymptotic analysis in the ratio between the difference of the widest and the
      most narrow constriction divided through the period length of the channel
      geometry. We demonstrate that the leading-order term is equivalent to the Fick
      Jacobs approximation. By use of the higher-order corrections to the probability
      density we show that in the diffusion-dominated regime the average transport
      velocity is obtained as the product of the zeroth-order Fick-Jacobs result and
      the expectation value of the spatially dependent diffusion coefficient D(x),
      which substitutes the constant diffusion coefficient in the common Fick-Jacobs
      equation. The analytic findings are corroborated with the precise numerical
      results of a finite element calculation of the Smoluchowski diffusive particle
      dynamics occurring in a reflection symmetric sinusoidal-shaped channel.

PMID- 21728519
TI  - Critical scaling near jamming transition for frictional granular particles.
AB  - The critical rheology of sheared frictional granular materials near jamming
      transition is numerically investigated. It is confirmed that there exists a true
      critical density which characterizes the onset of the yield stress and two
      fictitious critical densities which characterize the scaling laws of rheological
      properties. We find the existence of a hysteresis loop between two of the
      critical densities for each friction coefficient. It is noteworthy that the
      critical scaling law for frictionless jamming transition seems to be still valid
      even for frictional jamming despite using fictitious critical density values.

PMID- 21728520
TI  - Droplet and cluster formation in freely falling granular streams.
AB  - Particle beams are important tools for probing atomic and molecular interactions.
      Here we demonstrate that particle beams also offer a unique opportunity to
      investigate interactions in macroscopic systems, such as granular media.
      Motivated by recent experiments on streams of grains that exhibit liquid-like
      breakup into droplets, we use molecular dynamics simulations to investigate the
      evolution of a dense stream of macroscopic spheres accelerating out of an opening
      at the bottom of a reservoir. We show how nanoscale details associated with
      energy dissipation during collisions modify the stream's macroscopic behavior. We
      find that inelastic collisions collimate the stream, while the presence of short
      range attractive interactions drives structure formation. Parameterizing the
      collision dynamics by the coefficient of restitution (i.e., the ratio of relative
      velocities before and after impact) and the strength of the cohesive interaction,
      we map out a spectrum of behaviors that ranges from gaslike jets in which all
      grains drift apart to liquid-like streams that break into large droplets
      containing hundreds of grains. We also find a new, intermediate regime in which
      small aggregates form by capture from the gas phase, similar to what can be
      observed in molecular beams. Our results show that nearly all aspects of stream
      behavior are closely related to the velocity gradient associated with vertical
      free fall. Led by this observation, we propose a simple energy balance model to
      explain the droplet formation process. The qualitative as well as many
      quantitative features of the simulations and the model compare well with
      available experimental data and provide a first quantitative measure of the role
      of attractions in freely cooling granular streams.

PMID- 21728521
TI  - Critical role of friction for a single particle falling through a funnel.
AB  - We investigate a single frictional, inelastic, spherical particle falling under
      gravity through a symmetric funnel. A recent study showed that, for a
      frictionless particle in such a system, several anomalous phenomena occur: The
      particle can stay longer, lose more energy, and exert more impulsive force in a
      funnel with steeper walls. For frictionless particles, such phenomena exist for
      many small ranges of funnel angles and are a consequence of the many possible
      repeated patterns in particle trajectories. However, in reality, friction always
      exists and it is a natural question whether the anomalous phenomena still exist
      for frictional particles in such systems. We show that, surprisingly, the
      inclusion of friction in the dynamics actually dramatically enhances the
      anomalous phenomena. For frictional particles, the anomalous phenomena exist for
      all funnel angles steeper than 45^{ degrees } and are thus more robust than the
      frictionless case. Furthermore, instead of many possible complicated repeated
      patterns in particle trajectories, there is a unique repeated pattern for
      frictional particles. Moreover, this is the simplest possible repeated pattern.
      We derive an analytical expression for this unique repeated pattern and provide a
      theoretical explanation for the anomalous phenomena observed in frictional
      particle systems. We further show that the friction, no matter how small, plays a
      critical role in the dynamics, that is, the dynamics of the frictionless particle
      system is singular.

PMID- 21728522
TI  - Hysteresis in a hydrodynamic model of dense granular flows.
AB  - A hydrodynamic model for dense granular flows, previously developed for confined
      flows, has been extended to address free surface flow down an inclined chute.
      Results show that the model can predict the existence of two critical inclination
      angles, namely, the avalanche starting angle theta(start) above which the
      granular bed begins flowing from an initially jammed configuration, and an
      avalanche stopping angle theta(stop), which is the minimum to maintain flowing
      conditions, in agreement with experiments and numerical simulations available
      from the literature. The dependence of these critical angles on the bed depth is
      also analytically formulated, reflecting the expected qualitative behavior. Such
      a hysteretic behavior is specific of granular flow and its prediction provides
      indications of consistence of the modeling approach. The improved model also
      captures the scaling of the velocity profiles down the bed depth.

PMID- 21728523
TI  - Defining random loose packing for nonspherical grains.
AB  - The concept of "random loose packing" (RLP) has evolved through extensive study
      of loose packings of spheres, which has resulted in an accepted definition as the
      loosest packing that can be obtained by pouring grains. We extend this
      consideration to packings of nonspherical grains (ellipsoids) formed by slow
      settling in a viscous liquid, and perform a detailed analysis of the structural
      properties of the resulting packings. We find that as in the case of spheres the
      loosest ellipsoid packings are generated for grains with high interparticle
      friction. However, unlike spheres, these packings cannot be considered random as
      they have a significant degree of orientational ordering that increases with the
      grain's aspect ratio. This demonstrates that applying sedimentation or pouring
      techniques that have become part of the commonly held definition of RLP, will not
      generate random packings of ellipsoids. The consequences for the accepted
      definition of RLP and its applicability to nonspherical grains is discussed.

PMID- 21728524
TI  - Approximate hard-sphere method for densely packed granular flows.
AB  - The simulation of granular media is usually done either with event-driven codes
      that treat collisions as instantaneous but have difficulty with very dense
      packings, or with molecular dynamics (MD) methods that approximate rigid grains
      using a stiff viscoelastic spring. There is a little-known method that combines
      several collision events into a single timestep to retain the instantaneous
      collisions of event-driven dynamics, but also be able to handle dense packings.
      However, it is poorly characterized as to its regime of validity and failure
      modes. We present a modification of this method to reduce the introduction of
      overlap error, and test it using the problem of two-dimensional (2D) granular
      Couette flow, a densely packed system that has been well characterized by
      previous work. We find that this method can successfully replicate the results of
      previous work up to the point of jamming, and that it can do so a factor of 10
      faster than comparable MD methods.

PMID- 21728525
TI  - Flowers in flour: avalanches in cohesive granular matter.
AB  - We report on the intermittent dynamics of the free surface of a cohesive granular
      material during a silo discharge. In absence of cohesion, one observes the
      formation and the growth of a conical crater whose angle is well defined and
      constant in time. When the cohesion is involved the free surface exhibits a
      complex dynamics and the crater, resulting from a series of individual
      avalanches, is no longer axisymmetric. However, in spite of the intermittent
      behavior of the free surface, the flow rate is observed to remain constant
      throughout the discharge.

PMID- 21728526
TI  - Hyperuniformity, quasi-long-range correlations, and void-space constraints in
      maximally random jammed particle packings. I. Polydisperse spheres.
AB  - Hyperuniform many-particle distributions possess a local number variance that
      grows more slowly than the volume of an observation window, implying that the
      local density is effectively homogeneous beyond a few characteristic length
      scales. Previous work on maximally random strictly jammed sphere packings in
      three dimensions has shown that these systems are hyperuniform and possess
      unusual quasi-long-range pair correlations decaying as r(-4), resulting in
      anomalous logarithmic growth in the number variance. However, recent work on
      maximally random jammed sphere packings with a size distribution has suggested
      that such quasi-long-range correlations and hyperuniformity are not universal
      among jammed hard-particle systems. In this paper, we show that such systems are
      indeed hyperuniform with signature quasi-long-range correlations by
      characterizing the more general local-volume-fraction fluctuations. We argue that
      the regularity of the void space induced by the constraints of saturation and
      strict jamming overcomes the local inhomogeneity of the disk centers to induce
      hyperuniformity in the medium with a linear small-wave-number nonanalytic
      behavior in the spectral density, resulting in quasi-long-range spatial
      correlations scaling with r(-(d+1)) in d Euclidean space dimensions. A numerical
      and analytical analysis of the pore-size distribution for a binary maximally
      random jammed system in addition to a local characterization of the n-particle
      loops governing the void space surrounding the inclusions is presented in support
      of our argument. This paper is the first part of a series of two papers
      considering the relationships among hyperuniformity, jamming, and regularity of
      the void space in hard-particle packings.

PMID- 21728527
TI  - Hyperuniformity, quasi-long-range correlations, and void-space constraints in
      maximally random jammed particle packings. II. Anisotropy in particle shape.
AB  - We extend the results from the first part of this series of two papers by
      examining hyperuniformity in heterogeneous media composed of impenetrable
      anisotropic inclusions. Specifically, we consider maximally random jammed (MRJ)
      packings of hard ellipses and superdisks and show that these systems both possess
      vanishing infinite-wavelength local-volume-fraction fluctuations and quasi-long
      range pair correlations scaling as r(-(d+1)) in d Euclidean dimensions. Our
      results suggest a strong generalization of a conjecture by Torquato and
      Stillinger [Phys. Rev. E 68, 041113 (2003)], namely, that all strictly jammed
      saturated packings of hard particles, including those with size and shape
      distributions, are hyperuniform with signature quasi-long-range correlations. We
      show that our arguments concerning the constrained distribution of the void space
      in MRJ packings directly extend to hard-ellipse and superdisk packings, thereby
      providing a direct structural explanation for the appearance of hyperuniformity
      and quasi-long-range correlations in these systems. Additionally, we examine
      general heterogeneous media with anisotropic inclusions and show unexpectedly
      that one can decorate a periodic point pattern to obtain a hard-particle system
      that is not hyperuniform with respect to local-volume-fraction fluctuations. This
      apparent discrepancy can also be rationalized by appealing to the irregular
      distribution of the void space arising from the anisotropic shapes of the
      particles. Our work suggests the intriguing possibility that the MRJ states of
      hard particles share certain universal features independent of the local
      properties of the packings, including the packing fraction and average contact
      number per particle.

PMID- 21728528
TI  - Asymptotic analysis of stresses near a crack tip in a two-dimensional colloidal
      packing saturated with liquid.
AB  - The consolidation of colloidal particles in drying colloidal dispersions is
      influenced by various factors such as particle size and shape, and interparticle
      potential. The capillary pressure induced by the menisci, formed between the top
      layer of particles in the packed bed, compresses the bed of particles while the
      constraints imposed by the boundaries result in tensile stresses in the packing.
      Presence of flaws or defects in the bed determines its ultimate strength under
      such circumstances. In this study, we determine the asymptotic stress
      distribution around a flaw in a two-dimensional colloidal packing saturated with
      liquid and compare the results with those obtained from the full numerical
      solution of the problem. Using the Griffith's criterion for equilibrium cracks,
      we relate the critical capillary pressure at equilibrium to the crack size and
      the mechanical properties of the packed bed. The analysis also gives the maximum
      allowable flaw size for obtaining a crack-free packing.

PMID- 21728529
TI  - Self-diffusion of biomolecules in solution.
AB  - A simple soft-core model potential is proposed to discuss the self-diffusion of
      biomolecules in solution. Extensive Brownian-dynamics simulations are performed
      to obtain the long-time self-diffusion coefficient. Then the simulation results
      are compared with the experimental data from a unified point of view recently
      obtained for suspensions of hard spheres. Thus, it is shown that the proposed
      potential can qualitatively well describe the experimental data.

PMID- 21728530
TI  - Aggregation of frictional particles due to capillary attraction.
AB  - Capillary attraction between identical millimeter-sized spheres floating at a
      liquid-air interface and the resulting aggregation are investigated at low
      Reynolds number. We show that the measured capillary forces between two spheres
      as a function of distance can be described by expressions obtained using the
      Nicolson approximation at low Bond numbers for far greater particle sizes than
      previously assumed. We find that viscous hydrodynamic interactions between the
      spheres needs to be included to describe the dynamics close to contact. We then
      consider the aggregates formed when a third sphere is added after the initial two
      spheres are already in contact. In this case, we find that linear superposition
      of capillary forces describes the observed approach qualitatively but not
      quantitatively. Further, we observe an angular dependence of the structure due to
      a rapid decrease of capillary force with distance of separation, which has a
      tendency to align the particles before contact. When the three particles come
      into contact, they may preserve their shape or rearrange to form an equilateral
      triangle cluster-the lowest-energy state-depending on the competition between
      attraction between particles and friction. Using these observations, we
      demonstrate that a linear particle chain can be built from frictional particles
      with capillary attraction.

PMID- 21728531
TI  - Density invariant vibrational modes in disordered colloidal crystals.
AB  - We experimentally measure the density of states (DOS) and dynamical structure
      factor (DSF) arising from the thermal fluctuations in a colloidal crystal
      composed of thermally sensitive micron-sized hydrogel particles at several
      different particle volume fractions, phi's. Particle positions are tracked over
      long times using optical microscopy and particle tracking algorithms in a single
      two-dimensional (2D) [111] plane of a 3D face-centered-cubic single crystal. The
      dynamical fluctuations are spatially heterogeneous while the lattice itself is
      highly ordered. At all phi's, the DOS exhibits an excess of low frequency modes,
      a so-called boson peak (BP), and the DSF exhibits a cross-over from propagating
      to nonpropagating behavior, a so-called Ioffe-Regel crossover, at a frequency
      somewhat below the BP for both longitudinal and transverse modes. As we tune phi
      from 0.64 to 0.56, the Lindemann parameter grows from ~3% to ~8%; however, the
      shape of the DOS and DSF remain largely unchanged when rescaled by the Debye
      level. This invariance indicates that the effective degree of disorder remains
      essentially constant even in the vicinity of melting.

PMID- 21728532
TI  - Seed- and wall-induced heterogeneous nucleation in charged colloidal model
      systems under microgravity.
AB  - Understanding the process that drives an undercooled fluid to the crystal state
      is still a challenging issue for condensed matter physics and plays a key role in
      designing new materials. The crystallization kinetics and the resulting
      polycrystalline morphology are given by a complex interplay of crystal
      nucleation, growth, and ripening. A great deal of progress has been made in
      recent years using colloidal suspensions as model systems in the study of
      crystallization. Close analogies to atomic systems are observed which can be
      exploited to address questions not accessible in atomic solidification. Here we
      present systematic measurements of the crystallization kinetics of a charged
      colloidal model system adding small amounts of seeds using time resolved
      scattering techniques. Large seeds show strong sedimentation under gravity even
      on the time scale of the crystallization process. To avoid this problem we
      performed our measurements under microgravity during parabolic flights. We report
      how the seed size and structure affect crystal nucleation and growth as functions
      of metastability giving the possibility to modify the crystallization process and
      the resulting microstructure of the polycrystal.

PMID- 21728533
TI  - Three-dimensional arrays of submicron particles generated by a four-beam optical
      lattice.
AB  - Using an optical lattice formed by four laser beams, we obtain three-dimensional
      light-induced crystals of 490-nm-diameter polystyrene spheres in solution. The
      setup yields face-centered orthorhombic optical crystals of a packing density of
      about 40%. An alignment procedure is developed in which the crystals are first
      prepared near a sample wall, and then in the bulk of the sample. A series of
      tests is performed that demonstrate particle trapping in all three dimensions.
      For one case, the trapping force is measured, and good agreement with a simple
      theoretical model is found. Possible applications are discussed.

PMID- 21728534
TI  - Analysis of a growing dynamic length scale in a glass-forming binary hard-sphere
      mixture.
AB  - We examine a length scale that characterizes the spatial extent of heterogeneous
      dynamics in a glass-forming binary hard-sphere mixture up to the mode-coupling
      volume fraction phi(c). First, we characterize the system's dynamics. Then, we
      utilize a method [Phys. Rev. Lett. 105, 217801 (2010)] to extract and analyze the
      ensemble-independent dynamic susceptibility chi(4)(t) and the dynamic correlation
      length xi(t) for a range of times between the beta and alpha relaxation times. We
      find that in this time range the dynamic correlation length follows a volume
      fraction-independent master curve xi(t)~ln(t). For longer times, xi(t) departs
      from this master curve and remains constant up to the largest time at which we
      can determine the length accurately. In addition to the previously established
      correlation tau(alpha)~exp[xi(tau(alpha))] between the alpha relaxation time,
      tau(alpha), and the dynamic correlation length at this time, xi(tau(alpha)), we
      also find a similar correlation for the diffusion coefficient
      D~exp[xi(tau(alpha))(theta)] with theta~0.6. We discuss the relevance of these
      findings for different theories of the glass transition.

PMID- 21728535
TI  - Nanoscale domains with nematic order in supercooled vitamin-A acetate: molecular
      dynamics studies.
AB  - Vitamin-A acetate is one of the most versatile vitamins. It is applied in
      medicine because of its antioxidative properties, in tumor therapy because of its
      cytostatic activity, and in cosmetics because of its nutritional additives.
      Herein, using broadband dielectric spectroscopy, the molecular dynamics of
      supercooled and glassy vitamin-A acetate was investigated. It was shown that
      dielectric measurements carried out at ambient and elevated pressures reveal a
      number of relaxation processes associated with different types of molecular
      motions: alpha, delta, and nu processes-observed above the glass transition
      temperature and the next two modes: beta and gamma identified in the glassy
      state. The occurrence of the delta mode in the dielectric spectrum may imply the
      existence of nanoscale domains with nematic order. This hypothesis is further
      checked by atomic force microscopy measurements. Finally, we have determined the
      value of the glass transition temperature (T(g)) as well as the steepness index
      (m(P)) at various T-P conditions.

PMID- 21728536
TI  - Systematic study of the glass transition in polyhydric alcohols.
AB  - We have investigated the glass transitions of trihydric alcohols using broadband
      dielectric spectroscopy, and compare the results with those previously reported
      for sugar alcohols. Although a systematic glass transition feature related to
      molecular size has been reported for sugar alcohols, the essential factor
      governing this feature is still unclear because the number of carbon atoms (N(C))
      and the number of OH groups (N(OH)) per molecule are identical in sugar alcohols.
      By examining trihydric alcohols (N(C)?N(OH)), we conclude that N(OH) is dominant
      for the characteristics of the slow dynamics, such as fragility and glass
      transition temperature. This result suggests that the topological structure of
      the hydrogen-bonding network (coordination number) plays an important role in the
      glass transition of polyhydric alcohols. Furthermore, the orientational
      correlation factor evaluated using the Kirkwood-Frohlich theory reveals a
      similarity in hydrogen bond formation among a variety of polyhydric alcohols.
      Based on these two experimental results, we discuss a possible physical picture
      of the glass transition of polyhydric alcohols.

PMID- 21728537
TI  - Effect of particle size on the glass transition.
AB  - The glass transition temperature of a broad class of molecules is shown to depend
      on molecular size. This dependency results from the size dependence of the pair
      potential. A generalized equation of state is used to estimate how the volume
      fraction at the glass transition depends on the size of the molecule, for rigid
      molecule glass-formers. The model shows that at a given pressure and temperature
      there is a size-induced glass transition: For molecules larger than a critical
      size, the volume fraction required to support the effective pressure due to
      particle attractions is above that which characterizes the glassy state. This
      observation establishes the boundary between nanoparticles, which exist in liquid
      form only as dispersions in low molecular weight solvents and large molecules
      which form liquids that have viscosities below those characterized by the glassy
      state.

PMID- 21728538
TI  - Locally preferred structures and many-body static correlations in viscous
      liquids.
AB  - The influence of static correlations beyond the pair level on the dynamics of
      selected model glass formers is investigated. The pair structure, angular
      distribution functions, and statistics of Voronoi polyhedra of two well-known
      Lennard-Jones mixtures as well as of the corresponding Weeks-Chandler-Andersen
      variants, in which the attractive part of the potential is truncated, are
      compared. By means of the Voronoi construction, the atomic arrangements
      corresponding to the locally preferred structures of the models are identified.
      It is found that the growth of domains formed by interconnected locally preferred
      structures signals the onset of the slow-dynamics regime and allows the
      rationalization of the different dynamic behaviors of the models. At low
      temperature, the spatial extension of the structurally correlated domains,
      evaluated at fixed relaxation time, increases with the fragility of the models
      and is systematically reduced by truncating the attractions. In view of these
      results, proper inclusion of many-body static correlations in theories of the
      glass transition appears crucial for the description of the dynamics of fragile
      glass formers.

PMID- 21728539
TI  - Free-energy functional for freezing transitions: hard-sphere systems freezing
      into crystalline and amorphous structures.
AB  - A free-energy functional that contains both the symmetry-conserved and symmetry
      broken parts of the direct pair correlation function has been used to investigate
      the freezing of a system of hard spheres into crystalline and amorphous
      structures. The freezing parameters for fluid-crystal transition have been found
      to be in very good agreement with the results found from simulations. We
      considered amorphous structures found from molecular dynamics simulations at
      packing fractions eta lower than the glass close packing fraction eta(J) and
      investigated their stability compared to that of a homogeneous fluid. The
      existence of a free-energy minimum corresponding to a density distribution of
      overlapping Gaussians centered around an amorphous lattice depicts a deeply
      supercooled state with a heterogeneous density profile.

PMID- 21728540
TI  - Droplet evolution in expanding flow of warm dense matter.
AB  - We propose a simple, self-consistent kinetic model for the evolution of a mixture
      of droplets and vapor expanding adiabatically in vacuum after rapid, almost
      isochoric heating. We study the evolution of the two-phase fluid at intermediate
      times between the molecular and the hydrodynamic scales, focusing on out-of
      equilibrium and surface effects. We use the van der Waals equation of state as a
      test bed to implement our model and study the phenomenology of the upcoming
      second neutralized drift compression experiment (NDCX-II) at Lawrence Berkeley
      National Laboratory (LBNL) that uses ion beams for target heating. We find an
      approximate expression for the temperature difference between the droplets and
      the expanding gas and we check it with numerical calculations. The formula
      provides a useful criterion to distinguish the thermalized and nonthermalized
      regimes of expansion. In the thermalized case, the liquid fraction grows in a
      proportion that we estimate analytically, whereas, in case of too rapid
      expansion, a strict limit for the evaporation of droplets is derived. The range
      of experimental situations is discussed.

PMID- 21728541
TI  - Mesoscale modeling of the water liquid-vapor interface: a surface tension
      calculation.
AB  - We report a mesoscale modeling of the liquid-vapor interface of water. A
      mesoscopic model of water has been established in dissipative particle dynamics
      (DPD) to reproduce the interfacial properties of water. The surface tension and
      coexisting densities are compared between atomistic and mesoscopic simulations.
      Simple scaling relations have been established to link the atomistic and
      mesoscopic length and time scales. Our study demonstrates the capability of the
      DPD method to explore the interfacial properties of a planar water liquid-vapor
      interface and a water nanodroplet. This constitutes an important step toward the
      calculation of the surface tension of larger and more complex interfacial
      systems.

PMID- 21728542
TI  - Order-of-magnitude increase in flow velocity driven by mass conservation during
      the evaporation of sessile drops.
AB  - We report on a dramatic order-of-magnitude increase in flow velocity within
      pinned evaporating droplets toward the end of their lifetime. The measurements
      were performed using high-speed microparticle image velocimetry. The study
      revealed interesting observations about the spatial and temporal evolution of the
      velocity field. The profile along the radius of the droplet is found to exhibit a
      maximum toward the three phase contact line with flow oscillations in time in
      this region. Additional optical measurements allowed further analysis of the
      observed trends. Analysis of the potential mechanisms responsible for the flow
      within the droplet demonstrated that these observations can be satisfactorily
      explained and accounted for by mass conservation within the droplet to compensate
      for evaporation.

PMID- 21728543
TI  - Interplay of internal stresses, electric stresses, and surface diffusion in
      polymer films.
AB  - We investigate two destabilization mechanisms for elastic polymer films and put
      them into a general framework: first, instabilities due to in-plane stress and,
      second, due to an externally applied electric field normal to the film's free
      surface. As shown recently, polymer films are often stressed due to out-of
      equilibrium fabrication processes such as, e.g., spin coating. Via an Asaro
      Tiller-Grinfeld mechanism as known from solids, the system can decrease its
      energy by undulating its surface by surface diffusion of polymers and thereby
      relaxing stresses. On the other hand, application of an electric field is widely
      used experimentally to structure thin films; when the electric Maxwell surface
      stress overcomes surface tension and elastic restoring forces, the system
      undulates with a wavelength determined by the film thickness. We develop a theory
      taking into account both mechanisms simultaneously and discuss their interplay
      and the effects of the boundary conditions both at the substrate and at the free
      surface.

PMID- 21728544
TI  - Morphologies from slippery ballistic deposition model: a bottom-up approach for
      nanofabrication.
AB  - We report pattern formation using a slippery ballistic deposition (SBD) model
      where growth germinates from a single site or from sites distributed periodically
      on a lattice. By changing the sticking probability p(s) and choosing systems with
      different lattice constants and symmetries, we demonstrate that a variety of
      patterns can be generated. These patterns can be further used as scaffolds for
      nanofabrication. We also demonstrate that by choosing a lateral sticking
      probability p(l) at the base that is different than p(s), one can control both
      the early and late time morphologies originating from a seed. Furthermore, we
      indicate a possible generalization of preparing patterns to higher dimensions
      that in principle can have potential technological applications for preparing
      grooves and scaffolds of specific shapes and periodicities.

PMID- 21728545
TI  - Structural reordering in monolayers of gold nanoparticles during transfer from
      water surface to solid substrate.
AB  - Structural reordering in monolayers of gold nanoparticles during transfer from
      water surface to solid substrate has been studied by synchrotron x-ray scattering
      techniques. Grazing incidence diffraction (GID) and grazing incidence x-ray off
      specular scattering (GIXOS) measurements were performed as a function of time to
      track the in-plane and out-of-plane structural reordering in the transferred
      monolayers. GID measurements show shift in the in-plane particle-particle
      correlation peak toward the lower in-plane momentum transfer value, signifying
      possible expansion of triangular lattice formed on the water surface. However,
      GIXOS data and supportive microscopy measurements clearly show compactification
      in the in-plane structure and associated out-of-plane movements. A model that
      assumes the possibility of a two-dimensional short-range structural reordering
      from triangular to square-like lattice as a function of time could explain all
      the data. The observed change in the electron densities of the nanoparticles
      before and after the structural reordering matches well with the expected change
      in the calculated electron densities of the nanoparticles arranged in triangular
      (pretransition) and square-like (post-transition) symmetry.

PMID- 21728546
TI  - Lipid aggregate formation at an oscillating bubble surface: a simulation study.
AB  - We perform a molecular dynamics simulation study of the behavior of a lipid
      coating layer on an oscillating bubble surface. Micrometer sized bubbles,
      stabilized with a lipid monolayer coating, are used in acoustic imaging as a
      contrast agent. The coating layer is expected to be strongly influenced by the
      oscillation of the bubble in the high frequency sound field, with a period of a
      microsecond. The typical time scale of molecular motion, however, is of the order
      of femtoseconds. One of the challenges is to bridge this nine decade gap in time
      scales. To this end we have developed a model that is highly coarse grained, but
      still features the essential mechanisms determining lipid dynamics, with time
      scales of picoseconds. This approach allows us to severely restrict the computing
      times, although we make use of very modest computing equipment. We show in our
      simulation that the amphiphilic monolayer folds upon contraction of the bubble,
      and forms micellar aggregates at the air-water interface. Some micellar
      structures survive consecutive re-expansion and indeed remain persistent over
      several cycles. These structures may add to the anisotropic behavior of the
      bubbles under oscillating conditions. We also investigated temperature and
      frequency dependence.

PMID- 21728547
TI  - Aggregation according to classical kinetics: from nucleation to coarsening.
AB  - A previous paper [Y. Farjoun and J. C. Neu, Phys. Rev. E 78, 051402 (2008)]
      presents a simple kinetic model of the initial creation transient, starting from
      pure monomer. During this transient the majority of clusters are created, and the
      distribution of cluster sizes that emerges from it is predicted to be
      discontinuous at the largest cluster size. It is well known that the further
      evolution according to the Lifshitz-Slyozov model of coarsening preserves this
      discontinuity. The result is at odds with the original proposal of Lifshitz and
      Slyozov, that the physical late-stage coarsening distribution is the smooth one.
      The current paper presents an analytic-numerical solution of the Lifshitz-Slyozov
      equations, starting from the discontinuous creation distribution. Of course, this
      analysis selects the discontinuous late-stage coarsening distribution, but there
      is much more. It resolves the intermediate stages between the creation transient
      and late-state coarsening and provides specific scales of time and cluster size
      that characterize the onset of coarsening.

PMID- 21728548
TI  - Theoretical and numerical study of lamellar eutectic three-phase growth in
      ternary alloys.
AB  - We investigate lamellar three-phase patterns that form during the directional
      solidification of ternary eutectic alloys in thin samples. A distinctive feature
      of this system is that many different geometric arrangements of the three phases
      are possible, contrary to the widely studied two-phase patterns in binary
      eutectics. Here, we first analyze the case of stable lamellar coupled growth of a
      symmetric model ternary eutectic alloy, using a Jackson-Hunt-type calculation in
      thin film geometry, for arbitrary configurations, and derive expressions for the
      front undercooling as a function of velocity and spacing. Next, we carry out
      phase-field simulations to test our analytic predictions and to study the
      instabilities of the simplest periodic lamellar arrays. For large spacings, we
      observe different oscillatory modes that are similar to those found previously
      for binary eutectics and that can be classified using the symmetry elements of
      the steady-state pattern. For small spacings, we observe a new instability that
      leads to a change in the sequence of the phases. Its onset can be well predicted
      by our analytic calculations. Finally, some preliminary phase-field simulations
      of three-dimensional growth structures are also presented.

PMID- 21728549
TI  - Bubble nucleation in stout beers.
AB  - Bubble nucleation in weakly supersaturated solutions of carbon dioxide-such as
      champagne, sparkling wines, and carbonated beers-is well understood. Bubbles grow
      and detach from nucleation sites: gas pockets trapped within hollow cellulose
      fibers. This mechanism appears not to be active in stout beers that are
      supersaturated solutions of nitrogen and carbon dioxide. In their canned forms
      these beers require additional technology (widgets) to release the bubbles which
      will form the head of the beer. We extend the mathematical model of bubble
      nucleation in carbonated liquids to the case of two gases and show that this
      nucleation mechanism is active in stout beers, though substantially slower than
      in carbonated beers and confirm this by observation. A rough calculation suggests
      that despite the slowness of the process, applying a coating of hollow porous
      fibers to the inside of a can or bottle could be a potential replacement for
      widgets.

PMID- 21728550
TI  - Nonlinear smectic elasticity of helical state in cholesteric liquid crystals and
      helimagnets.
AB  - General symmetry arguments, dating back to de Gennes, dictate that at scales
      longer than the pitch, the low-energy elasticity of a chiral nematic liquid
      crystal (cholesteric) and of a Dzyaloshinskii-Morya (DM) spiral state in a
      helimagnet with negligible crystal symmetry fields (e.g., MnSi, FeGe) is
      identical to that of a smectic liquid crystal, thereby inheriting its rich
      phenomenology. Starting with a chiral Frank free energy (exchange and DM
      interactions of a helimagnet) we present a transparent derivation of the fully
      nonlinear Goldstone mode elasticity, which involves an analog of the Anderson
      Higgs mechanism that locks the spiral orthonormal (director or magnetic moment)
      frame to the cholesteric (helical) layers. This shows explicitly the reduction of
      three orientational modes of a cholesteric down to a single-phonon Goldstone mode
      that emerges on scales longer than the pitch. At a harmonic level our result
      reduces to that derived many years ago by Lubensky and collaborators.

PMID- 21728551
TI  - Geometrical content of Leslie coefficients.
AB  - In this work, we will study how the effective geometry acquired by nematic
      molecules under thermal vibration contribute to the determination of the Leslie
      coefficients. To do this, we will divide this work in two sections. In the first
      section, we present the geometrical fundamentals of the so-called Hess-Baalss
      (HB) approach [D. Baalss and S. Hess, Phys. Rev. Lett. 57, 86 (1986)] where we
      show that its basic assumptions can be understood as a geometrical interpretation
      of de Gennes' passage from the microscopic to the macroscopic order parameter. In
      the second section, we use an extended version of the HB approach [M. Simoes, K.
      Yamaguti, and A. J. Palangana, Phys. Rev. E 80, 061701 (2009)] to obtain the
      geometrical contribution to each Leslie coefficient. Our results will be compared
      with experimental data, and we will show that the Miesowicz's coefficients are
      connected as long as the ratio alpha(3)/alpha(4) between these Leslie
      coefficients can be considered small.

PMID- 21728552
TI  - Modeling and simulation of liquid-crystal elastomers.
AB  - We consider a continuum model describing the dynamic behavior of nematic liquid
      crystal elastomers (LCEs) and implement a numerical scheme to solve the governing
      equations. In the model, the Helmholtz free energy and Rayleigh dissipation are
      used, within a Lagrangian framework, to obtain the equations of motion. The free
      energy consists of both elastic and liquid crystalline contributions, each of
      which is a function of the material displacement and the orientational order
      parameter. The model gives dynamics for the material displacement, the scalar
      order parameter and the nematic director, the latter two of which correspond to
      the orientational order parameter tensor. Our simulations are carried out by
      solving the governing equations using an implicit-explicit scheme and the
      Chebyshev polynomial method. The simulations show that the model can successfully
      capture the shape changing dynamics of LCEs that have been observed in
      experiments, and also track the evolution of the order parameter tensor.

PMID- 21728553
TI  - Role of stringlike, supramolecular assemblies in reentrant supernematic liquid
      crystals.
AB  - Using a combination of isothermal-isobaric Monte Carlo and microcanonical
      molecular dynamics we investigate the relation between structure and self
      diffusion in various phases of a model liquid crystal using the Gay-Berne-Kihara
      potential. These molecules are confined to a mesoscopic slit pore with atomically
      smooth substrate surfaces. As reported recently [seeM. G. Mazza et al., Phys.
      Rev. Lett. 105, 227802 (2010)], a reentrant nematic (RN) phase may form at
      sufficiently high pressures and densities. This phase is characterized by a high
      degree of nematic order and a substantially enhanced self-diffusivity in the
      direction of the director n that exceeds that of the lower-density nematic and an
      intermittent smectic-A phase by about an order of magnitude. Here we demonstrate
      that the unique transport behavior in the RN phase may be linked to a confinement
      induced packing effect that causes the formation of supramolecular, stringlike
      conformations. The strings consist of several molecules traveling in the
      direction of n as individual "trains" consisting of chains of molecular "cars."

PMID- 21728554
TI  - Biaxial-uniaxial transition in a self-assembled nematic liquid crystal by field
      induced molecular conformation.
AB  - A cylindrical uniaxial liquid crystal was hydrogen-bonded with a tripod-shaped
      molecule. As the molecular number ratio of cylindrical liquid crystal to tripod
      molecule converges to 2:1, |s| = 1/2 disclination defects, which are a necessary
      condition of biaxial nematic phase, appeared predominantly. After the application
      of an electric field, the |s| = 1/2 disclinations converted to |s| = 1
      disclinations which imply a transition from a biaxial to uniaxial state. IR
      dichroism measurements support the hypothesis that the liquid crystal-tripod
      molecule complex undergoes a molecular conformation change from bent shape to
      parallel shape, and this conformation change is thought to be related to a field
      induced biaxial-uniaxial transition.

PMID- 21728555
TI  - Flexoelectricity and pattern formation in nematic liquid crystals.
AB  - We present in this paper a detailed analysis of the flexoelectric instability of
      a planar nematic layer in the presence of an alternating electric field
      (frequency omega), which leads to stripe patterns (flexodomains) in the plane of
      the layer. This equilibrium transition is governed by the free energy of the
      nematic, which describes the elasticity with respect to the orientational degrees
      of freedom supplemented by an electric part. Surprisingly the limit omega->0 is
      highly singular. In distinct contrast to the dc case, where the patterns are
      stationary and time independent, they appear at finite, small omega periodically
      in time as sudden bursts. Flexodomains are in competition with the intensively
      studied electrohydrodynamic instability in nematics, which presents a
      nonequilibrium dissipative transition. It will be demonstrated that omega is a
      very convenient control parameter to tune between flexodomains and convection
      patterns, which are clearly distinguished by the orientation of their stripes.

PMID- 21728556
TI  - Direct nanomechanical measurement of layer thickness and compressibility of
      smectic liquid crystals.
AB  - Using an atomic force microscope (AFM) we confined a smectic-A liquid crystal
      (LC) between a flat glass plate and a 10-MUm glass sphere attached to the free
      end of the AFM cantilever. Both surfaces were treated with a surfactant that
      induces normal alignment of the LC molecules. We measured the force F acting on
      the cantilever while varying the plate-sphere distance D with subnanometer
      precision. For D < 50 nm, the force was periodically oscillating and decayed as D
      was increased. Analyzing the force in the framework of a simple model of elastic
      deformation of the smectic layers, we have evaluated the undeformed layer
      thickness a(0) and compressibility modulus B. Compared to other techniques used
      to determine a(0) and B, AFM measurements are faster and require a much smaller
      amount (microliters) of LC. Moreover, they are based on purely mechanical
      deformations of the LC structure and do not require any static or radiative
      electromagnetic field.

PMID- 21728557
TI  - Cooperative liquid-crystal alignment generated by overlaid topography.
AB  - Nematic and smectic liquid crystals were introduced into MUm-scale gaps between
      plates coated with polymer films nanoimprinted with parallel arrays of
      rectangular channels. Overlaying the channels on the two plates close enough at a
      slight angle produces a mosaic of alternating planar and homeotropic alignments
      and hybrid alignment, showing that complex liquid-crystal orientation patterns
      can be achieved by combining two simple topographic patterns. These alignment
      patterns are attributed to spatial variation of surface roughness and 3D
      topographic structure created by a sufficient proximity of the two patterns.

PMID- 21728558
TI  - Numerical evidence for nematic and smectic behavior of two-dimensional hard
      models.
AB  - The mesophases of two infinitely hard models with chiral and anisotropic
      characteristics in two dimensions are studied. Evidence for nematic and smectic
      behavior is provided via Monte Carlo simulations using restrictive values of the
      molecular parameters. Both models are geometrically chiral; one has polar
      structure. The concept of smectic phase considered in this work requires
      translational disorder in one direction and signs of translational order in the
      perpendicular one. The models presented in this paper show these characteristics.
      The isotropic-nematic phase transition satisfies the features of the Kosterlitz
      Thouless type. The smectic phase shows signs of quasi-long-range order.

PMID- 21728559
TI  - Computational analysis of molecular properties and spectral characteristics of
      cyano-containing liquid crystals: role of alkyl chains.
AB  - The electronic transitions in the uv-visible range of 4'-n-alkyl-4-cyanobiphenyl
      (nCB) with propyl, pentyl, and heptyl groups, which are of commercial and
      application interests, have been studied. The uv-visible and circular dichroism
      spectra of nCB (n = 3,5,7) molecules have been simulated using the time dependent
      density functional theory Becke3-Lee-Yang-Parr hybrid functional-6-31 + G (d)
      method. Mulliken atomic charges for each molecule have been compared with Loewdin
      atomic charges to analyze the molecular charge distribution and phase stability.
      The highest occupied molecular orbital and lowest unoccupied molecular orbital
      energies corresponding to the electronic transitions in the uv-visible range have
      been reported. Excited states have been calculated via the configuration
      interaction single level with a semiempirical Hamiltonian (intermediate neglect
      of differential overlap method, as parametrized by Zerner and co-workers).
      Further, two types of calculations have been performed for model systems
      containing single and double molecules of nCB. Furthermore, the dimer complexes
      during the different modes of molecular interactions have also been studied. The
      interaction energies of dimer complexes have been taken into consideration in
      order to investigate the most energetically stable configuration. These studies
      are helpful for understanding the role and flexibility of end chains, in
      particular, phase behavior and stability.

PMID- 21728560
TI  - Surface electroclinic effect near the first-order smectic-A*-smectic-C*
      transition.
AB  - We analyze the surface electroclinic effect (SECE) in a material that exhibits a
      first-order bulk smectic-A* (Sm-A*)-smectic-C* (Sm-C*) transition. The effect of
      a continuously varying degree of enantiomeric excess on the SECE is also
      investigated. We show that due to the first-order nature of the bulk Sm-A*-Sm-C*
      transition, the SECE can be unusually strong and that as enantiomeric excess is
      varied, a jump in surface induced tilt is expected. A theoretical state map, in
      enantiomeric excess-temperature space, features a critical point which terminates
      a line of first-order discontinuities in the surface induced tilt. This critical
      point is analogous to that found for the phase diagram (in electric field
      temperature space) for the bulk electroclinic effect. Analysis of the decay of
      the surface induced tilt, as one moves from surface into bulk, shows that for
      sufficiently high-surface tilt the decay will exhibit a well-defined spatial kink
      within which it becomes especially rapid. We also propose that the SECE is
      additionally enhanced by the de Vries nature (i.e., small layer shrinkage at the
      bulk Sm-A*-Sm-C* transition) of the material. As such, the SECE provides a new
      means to characterize the de Vries nature of a material. We discuss the
      implications for using these materials in device applications and propose ways to
      investigate the predicted features experimentally.

PMID- 21728561
TI  - Collision of polymers in a vacuum.
AB  - In a number of experimental situations, single-polymer molecules can be suspended
      in a vacuum. Here collisions between such molecules are considered. The limit of
      high collision velocity is investigated numerically for a variety of conditions.
      The distribution of contact times, scattering angles, and final velocities are
      analyzed. In this limit, self-avoiding chains are found to become highly
      stretched as they collide with each other and have a distribution of scattering
      times that depends on the scattering angle. The velocity of the molecules after
      the collisions is similar to predictions of a model assuming thermal
      equilibration of molecules during the collision. The most important difference is
      a significant subset of molecules that inelastically scatter but do not
      substantially change direction.

PMID- 21728562
TI  - Self-organized stiffness in regular fractal polymer structures.
AB  - We investigated membrane-like polymer structures of fractal connectivity such as
      Sierpinski gaskets and Sierpinski carpets applying the bond fluctuation model in
      three dimensions. Without excluded volume (phantom), both polymeric fractals obey
      Gaussian elasticity on larger scales determined by their spectral dimension. On
      the other hand, the swelling effect due to excluded volume is rather distinct
      between the two polymeric fractals: Self-avoiding Sierpinski gaskets can be
      described using a Flory-type mean-field argument. Sierpinski carpets having a
      spectral dimension closer to perfect membranes are significantly more strongly
      swollen than predicted. Based on our simulation results it cannot be excluded
      that Sierpinski carpets in athermal solvent show a flat phase on larger scales.
      We tested the self-consistency of Flory predictions using a virial expansion to
      higher orders. From this we conclude that the third virial coefficient
      contributes marginally to Sierpinski gaskets, but higher order virial
      coefficients are relevant for Sierpinski carpets.

PMID- 21728563
TI  - Network structure of polyfluorene sheets as a function of alkyl side chain
      length.
AB  - The formation of self-organized structures in poly(9,9-di-n-alkylfluorene)s ~1
      vol % methylcyclohexane (MCH) and deuterated MCH (MCH-d(14)) solutions was
      studied at room temperature using neutron and x-ray scattering (with the overall
      q range of 0.00058-4.29 A(-1)) and optical spectroscopy. The number of side chain
      carbons (N) ranged from 6 to 10. The phase behavior was rationalized in terms of
      polymer overlap, cross-link density, and blending rules. For N=6-9, the system
      contains isotropic areas and lyotropic areas where sheetlike assemblies (lateral
      size of >400 A) and free polymer chains form ribbonlike agglomerates
      (characteristic dimension of >1500 A) leading to a gel-like appearance of the
      solutions. The ribbons are largely packed together with surface fractal
      characteristics for N=6-7 but become open networklike structures with mass
      fractal characteristics for N=8-9, until the system goes through a transition to
      an isotropic phase of overlapping rodlike polymers for N=10. The polymer order
      within sheets varies allowing classification for loose membranes and ordered
      sheets, including the so-called beta phase. The polymers within the ordered
      sheets have restricted motion for N=6-7 but more freedom to vibrate for N=8-9.
      The nodes in the ribbon network are suggested to contain ordered sheets cross
      linking the ribbons together, while the nodes in the isotropic phase appear as
      weak density fluctuations cross-linking individual chains together. The
      tendencies for macrophase separation and the formation of non beta sheets
      decrease while the proportion of free chains increases with increasing N. The
      fraction of beta phase varies nonlinearly, reaching its maximum at N = 8.

PMID- 21728564
TI  - Role of diffusion in scaling of polymer chain aggregates found in vapor
      deposition polymerization.
AB  - Polymer chain aggregates grown by (1+1)-dimensional Monte Carlo simulations of
      vapor deposition polymerization (VDP) were studied. The dynamic scaling behavior
      of polymer chain length distribution n(s)(t) was studied as a function of chain
      length (s), deposition time (t), and the ratio G=D/F of deposition rate (F) and
      free monomer diffusion (D). The dynamic scaling approach was employed to
      highlight the dependence of n(s)(t) on t, s, and G. With an increase in t, we
      found a power law increase in n(s)(t) and total number of polymer chains
      N(total)(t), given by N(total)(t)~t(omega) and n(s)(t)~t(omega) with exponent
      omega=1.01(2) that was invariant for a range of G=10 to 10^{4}. For small s and
      t=10^{3}, 5*10^{3}, and 10^{4}, n_{s}(t) decreased according to n(s)(t)~s(-tau)
      with tau=0.58(2). As G was increased from 10 to 10(4), we observed a systematic
      influence of G on the rescaled n(s)(t) data that prevented the manifestation of
      unique scaling function for polymer chain aggregates. The dependence of scaling
      functions of n(s)(t) on G elucidates the sensitivity of polymer chain aggregates
      to G and is thought to be a characteristic of VDP.

PMID- 21728565
TI  - Temperature dependence on free volume in cured natural rubber and styrene
      butadiene rubber blends.
AB  - A systematic study on the evolution of free volume as a function of the
      temperature in vulcanized at 433 K natural rubber (NR) and styrene butadiene
      rubber (SBR) in 25-75, 50-50, 75-25 NR-SBR (percent content of pure NR and SBR,
      respectively) blends was studied by positron annihilation lifetime spectroscopy.
      All samples were prepared with sulfur and TBBS (n-t-butyl-2-benzothiazole
      sulfenamide) as accelerator. The glass transition temperatures of the samples
      studied were determined by differential scanning calorimetry (DSC) and from
      lifetime data. In general, a sigmoidal-like complex behavior of the long-lived
      lifetime component, linked to the nanohole free volume, as a function of the
      temperature was found. For SBR, the slope of the ortho-positronium lifetime
      against temperature curves could be well-fitted using a linear function. For
      blends and also for NR, two different linear functions were necessary. This last
      behavior is explained in terms of the supercooled process involving a
      reconfiguration of the elastomeric chains. In the case of blends, the state of
      cure of NR and SBR in each NR-SBR sample was also taken into account in the
      discussion of the results obtained. Besides, thermal expansion coefficients of
      the free volumes in the transition and glassy region of all compounds were
      estimated. The differences observed in the values of this parameter are discussed
      by taking into account the morphology and formulation of each blend, the
      crosslink densities, and the role of the interphases formed between both NR and
      SBR elastomers.

PMID- 21728566
TI  - Bistability and resonance in the periodically stimulated Hodgkin-Huxley model
      with noise.
AB  - We describe general characteristics of the Hodgkin-Huxley neuron's response to a
      periodic train of short current pulses with Gaussian noise. The deterministic
      neuron is bistable for antiresonant frequencies. When the stimuli arrive at the
      resonant frequency the firing rate is a continuous function of the current
      amplitude I(0) and scales as (I(0)-I(th))(1/2), characteristic of a saddle-node
      bifurcation at the threshold I(th). Intervals of continuous irregular response
      alternate with integer mode-locked regions with bistable excitation edge. There
      is an even-all multimodal transition between the 2 : 1 and 3 : 1 states in the
      vicinity of the main resonance, which is analogous to the odd-all transition
      discovered earlier in the high-frequency regime. For I(0)<I(th) and small noise
      the firing rate has a maximum at the resonant frequency. For larger noise and
      subthreshold stimulation the maximum firing rate initially shifts toward lower
      frequencies, then returns to higher frequencies in the limit of large noise. The
      stochastic coherence antiresonance, defined as a simultaneous occurrence of (i)
      the maximum of the coefficient of variation and (ii) the minimum of the firing
      rate vs the noise intensity, occurs over a wide range of parameter values,
      including monostable regions. Results of this work can be verified
      experimentally.

PMID- 21728567
TI  - Viscoelastic response of contractile filament bundles.
AB  - The actin cytoskeleton of adherent tissue cells often condenses into filament
      bundles contracted by myosin motors, so-called stress fibers, which play a
      crucial role in the mechanical interaction of cells with their environment.
      Stress fibers are usually attached to their environment at the endpoints, but
      possibly also along their whole length. We introduce a theoretical model for such
      contractile filament bundles which combines passive viscoelasticity with active
      contractility. The model equations are solved analytically for two different
      types of boundary conditions. A free boundary corresponds to stress fiber
      contraction dynamics after laser surgery and results in good agreement with
      experimental data. Imposing cyclic varying boundary forces allows us to calculate
      the complex modulus of a single stress fiber.

PMID- 21728568
TI  - Competition for hydrogen-bond formation in the helix-coil transition and protein
      folding.
AB  - The problem of the helix-coil transition of biopolymers in explicit solvents,
      such as water, with the ability for hydrogen bonding with a solvent is addressed
      analytically using a suitably modified version of the Generalized Model of
      Polypeptide Chains. Besides the regular helix-coil transition, an additional coil
      helix or reentrant transition is also found at lower temperatures. The reentrant
      transition arises due to competition between polymer-polymer and polymer-water
      hydrogen bonds. The balance between the two types of hydrogen bonding can be
      shifted to either direction through changes not only in temperature, but also by
      pressure, mechanical force, osmotic stress, or other external influences. Both
      polypeptides and polynucleotides are considered within a unified formalism. Our
      approach provides an explanation of the experimental difficulty of observing the
      reentrant transition with pressure and underscores the advantage of pulling
      experiments for studies of DNA. Results are discussed and compared with those
      reported in a number of recent publications with which a significant level of
      agreement is obtained.

PMID- 21728569
TI  - Three synaptic components contributing to robust network synchronization.
AB  - Robust synchronized activity is widely observed in real neural systems. However,
      a mechanism for robust synchronization that can be understood analytically, and
      has a clear physical meaning, remains elusive. This paper considers such a
      mechanism by formalizing three synaptic components contributing to robust
      synchronization in networks with heterogeneous external drive currents and
      conductance-based synapses. The first component arises from the assumption that
      the aggregate post-synaptic potential of a neuron decays more if it fires later
      within a spike volley. The second component results because neurons with smaller
      drives have reached a lower membrane potential at the time when the volley of
      inputs arrives than that reached by neurons with larger drives. The third
      component arises from the assumption that neurons firing later in the previous
      volley have had less time to integrate their drives than neurons firing earlier
      have had, again causing a lower membrane potential at the time when the volley of
      inputs arrives. Because of the voltage-dependent properties of synaptic currents,
      either of the last two components will cause smaller inhibitions for the later
      firing neurons if the synapses are inhibitory. This smaller inhibition causes the
      later-firing neurons to fire earlier in the next cycle, thereby forcing them
      toward synchrony. With these three synaptic components, we discuss the
      relationship between the robustness of the synchrony and the parameters, search
      for the optimal parameter set for the robust network synchronization of a certain
      frequency band, and demonstrate the key role of the voltage-dependent properties
      of synaptic currents in robust or stable synchronization.

PMID- 21728570
TI  - Formation of morphogen gradients: local accumulation time.
AB  - Spatial regulation of cell differentiation in embryos can be provided by
      morphogen gradients, which are defined as the concentration fields of molecules
      that control gene expression. For example, a cell can use its surface receptors
      to measure the local concentration of an extracellular ligand and convert this
      information into a corresponding change in its transcriptional state. We
      characterize the time needed to establish a steady-state gradient in problems
      with diffusion and degradation of locally produced chemical signals. A relaxation
      function is introduced to describe how the morphogen concentration profile
      approaches its steady state. This function is used to obtain a local accumulation
      time that provides a time scale that characterizes relaxation to steady state at
      an arbitrary position within the patterned field. To illustrate the approach we
      derive local accumulation times for a number of commonly used models of morphogen
      gradient formation.

PMID- 21728571
TI  - Communication-induced multistability and multirhythmicity in a synthetic
      multicellular system.
AB  - Traditionally, the main role of cell-to-cell communication was thought of as
      synchronizing a population of cells, thereby coordinating cellular behavior. Here
      we show that cell density, which quantifies cellular communication, can induce
      multistability and multirhythmicity in a synthetic multicellular system, where
      individual oscillators are a combination of repressillator and hysteresis-based
      oscillators and are coupled through a quorum-sensing mechanism. Specifically, for
      moderately small cell densities, the coupled system can exhibit multistability
      including stable homogenous and inhomogeneous steady states. For moderately large
      cell densities, it has the potential to generate multirhythmicity including
      multimode oscillations such as an in-phase periodic solution, antiphase periodic
      solution, asymmetric periodic solution, mixed-mode oscillations, coexistence of
      periodic orbits of several different modes, and bursting oscillations such as
      periodic bursting, torus quasiperiodic bursting, and chaotic bursting. Such
      versatility of cell-to-cell communication would be beneficial for cells or
      organisms to live in diversely changeable environments.

PMID- 21728572
TI  - Interaction between connectivity and oscillatory currents in a heterogeneous
      neuronal network.
AB  - Intrinsic oscillations are thought to play important and distinct roles in
      cognitive processes across nearly all regions of the brain. Their specific roles
      are highly dependent on their properties: low-frequency theta is thought to be
      important in the gating of cognitive processes, while high-frequency gamma is
      believed to be essential for binding and spike-timing-dependent plasticity. We
      investigated the role of an oscillatory drive for pattern formation of
      heterogeneous networks. Network heterogeneities were implemented as network
      regions having increased connectivity as compared to the rest of the network. We
      varied the properties of the oscillatory drive as well as network connectivity.
      We observed that the disparity in spatiotemporal patterning of activity between
      the structurally enhanced region and rest of the network was highly dependent on
      the frequency and amplitude of the oscillatory drive as well as network
      connectivity, generally favoring bigger enhancement of activity for high
      frequency oscillations and phase locking with moderate enhancement of activity
      for lower-frequency oscillations. Thus, these results indicate that the specific
      role of the observed oscillations may depend on their dynamical interactions with
      the heterogeneous network.

PMID- 21728573
TI  - Phase description of spiking neuron networks with global electric and synaptic
      coupling.
AB  - Phase models are among the simplest neuron models reproducing spiking behavior,
      excitability, and bifurcations toward periodic firing. However, coupling among
      neurons has been considered only using generic arguments valid close to the
      bifurcation point, and the differentiation between electric and synaptic coupling
      remains an open question. In this work we aim to address this question and derive
      a mathematical formulation for the various forms of coupling. We construct a
      mathematical model based on a planar simplification of the Morris-Lecar model.
      Based on geometric arguments we then derive a phase description of a network of
      the above oscillators with biologically realistic electric coupling and
      subsequently with chemical coupling under fast synapse approximation. We
      demonstrate analytically that electric and synaptic coupling are differently
      expressed on the level of the network's phase description with qualitatively
      different dynamics. Our mathematical analysis shows that a breaking of the
      translational symmetry in the phase flows is responsible for the different
      bifurcations paths of electric and synaptic coupling. Our numerical
      investigations confirm these findings and show excellent correspondence between
      the dynamics of the full network and the network's phase description.

PMID- 21728574
TI  - Deterministic microfluidic ratchet based on the deformation of individual cells.
AB  - We present a microfluidic ratchet that exploits the deformation of individual
      cells through microscale funnel constrictions. The threshold pressure required to
      transport single cells through such constrictions is greater against the
      direction of taper than along the direction of taper. This physical asymmetry
      combined with an oscillatory excitation can enable selective and irreversible
      transport of individual cells in low Reynolds number flow. We devised a
      microfluidic device to measure the pressure asymmetry across various geometries
      of funnel constrictions. Using a chain of funnel constrictions, we showed that
      oscillatory pressure enables ratcheting transport when the pressure amplitude and
      oscillation period exceeds the threshold required to transport single cells.
      These experiments demonstrate the potential of using this mechanism to
      selectively transport biological cells based on their internal mechanics, and the
      potential to separate cells based on cell morphology or disease state.

PMID- 21728575
TI  - Equivalence of quantum and classical coherence in electronic energy transfer.
AB  - To investigate the effect of quantum coherence on electronic energy transfer,
      which is the subject of current interest in photosynthesis, we solve the problem
      of transport for the simplest model of an aggregate of monomers interacting
      through dipole-dipole forces using both quantum and classical dynamics. We
      conclude that for realistic coupling strengths quantum and classical coherent
      transport are identical. This is demonstrated by numerical calculations for a
      linear chain and for the photosynthetic Fenna-Matthews-Olson complex.

PMID- 21728576
TI  - Neuron dynamics in the presence of 1/f noise.
AB  - Interest in understanding the interplay between noise and the response of a
      nonlinear device cuts across disciplinary boundaries. It is as relevant for
      unmasking the dynamics of neurons in noisy environments as it is for designing
      reliable nanoscale logic circuit elements and sensors. Most studies of noise in
      nonlinear devices are limited to either time-correlated noise with a Lorentzian
      spectrum (of which the white noise is a limiting case) or just white noise. We
      use analytical theory and numerical simulations to study the impact of the more
      ubiquitous "natural" noise with a 1/f frequency spectrum. Specifically, we study
      the impact of the 1/f noise on a leaky integrate and fire model of a neuron. The
      impact of noise is considered on two quantities of interest to neuron function:
      The spike count Fano factor and the speed of neuron response to a small steplike
      stimulus. For the perfect (nonleaky) integrate and fire model, we show that the
      Fano factor can be expressed as an integral over noise spectrum weighted by a
      (low-pass) filter function given by F(t,f)=sinc(2)(pift). This result elucidates
      the connection between low-frequency noise and disorder in neuron dynamics. Under
      1/f noise, spike dynamics lacks a characteristic correlation time, inducing the
      leaky and nonleaky models, to exhibit nonergodic behavior and the Fano factor,
      increasing logarithmically as a function of time. We compare our results to
      experimental data of single neurons in vivo [Teich, Heneghan, Lowen, Ozaki, and
      Kaplan, J. Opt. Soc. Am. A 14, 529 (1997)] and show how the 1/f noise model
      provides much better agreement than the usual approximations based on Lorentzian
      noise. The low-frequency noise, however, complicates the case for an information
      coding scheme based on interspike intervals by introducing variability in the
      neuron response time. On a positive note, the neuron response time to a step
      stimulus is, remarkably, nearly optimal in the presence of 1/f noise. An
      explanation of this effect elucidates how the brain can take advantage of noise
      to prime a subset of the neurons to respond almost instantly to sudden stimuli.

PMID- 21728577
TI  - Relation between cooperative molecular motors and active Brownian particles.
AB  - Active Brownian particles (ABPs), obeying a nonlinear Langevin equation with
      speed-dependent drift and noise amplitude, are well-known models used to describe
      self-propelled motion in biology. In this paper we study a model describing the
      stochastic dynamics of a group of coupled molecular motors (CMMs). Using two
      independent numerical methods, one based on the stationary velocity distribution
      of the motors and the other one on the local increments (also known as the
      Kramers-Moyal coefficients) of the velocity, we establish a connection between
      the CMM and the ABP models. The parameters extracted for the ABP via the two
      methods show good agreement for both symmetric and asymmetric cases and are
      independent of N, the number of motors, provided that N is not too small. This
      indicates that one can indeed describe the CMM problem with a simpler ABP model.
      However, the power spectrum of velocity fluctuations in the CMM model reveals a
      peak at a finite frequency, a peak which is absent in the velocity spectrum of
      the ABP model. This implies richer dynamic features of the CMM model which cannot
      be captured by an ABP model.

PMID- 21728578
TI  - Sequentially firing neurons confer flexible timing in neural pattern generators.
AB  - Neuronal networks exhibit a variety of complex spatiotemporal patterns that
      include sequential activity, synchrony, and wavelike dynamics. Inhibition is the
      primary means through which such patterns are implemented. This behavior is
      dependent on both the intrinsic dynamics of the individual neurons as well as the
      connectivity patterns. Many neural circuits consist of networks of smaller
      subcircuits (motifs) that are coupled together to form the larger system. In this
      paper, we consider a particularly simple motif, comprising purely inhibitory
      interactions, which generates sequential periodic dynamics. We first describe the
      dynamics of the single motif both for general balanced coupling (all cells
      receive the same number and strength of inputs) and then for a specific class of
      balanced networks: circulant systems. We couple these motifs together to form
      larger networks. We use the theory of weak coupling to derive phase models which,
      themselves, have a certain structure and symmetry. We show that this structure
      endows the coupled system with the ability to produce arbitrary timing
      relationships between symmetrically coupled motifs and that the phase
      relationships are robust over a wide range of frequencies. The theory is
      applicable to many other systems in biology and physics.

PMID- 21728579
TI  - Effects of surface roughness and film thickness on the adhesion of a bioinspired
      nanofilm.
AB  - Inspired by the gecko's climbing ability, adhesion between an elastic nanofilm
      with finite length and a rough substrate with sinusoidal roughness is studied in
      the present paper, considering the effects of substrate roughness and film
      thickness. It demonstrates that the normal adhesion force of the nanofilm on a
      rough substrate depends significantly on the geometrical parameters of the
      substrate. When the film length is larger than the wavelength of the sinusoidal
      roughness of the substrate, the normal adhesion force decreases with increasing
      surface roughness, while the normal adhesion force initially decreases then
      increases if the wavelength of roughness is larger than the film length. This
      finding is qualitatively consistent with a previously interesting experimental
      observation in which the adhesion force of the gecko spatula is found to reduce
      significantly at an intermediate roughness. Furthermore, it is inferred that the
      gecko may achieve an optimal spatula thickness not only to follow rough surfaces,
      but also to saturate the adhesion force. The results in this paper may be helpful
      for understanding how geckos overcome the influence of natural surface roughness
      and possess such adhesion to support their weights.

PMID- 21728580
TI  - Multiphoton fluorescence recovery after photobleaching in bounded systems.
AB  - Multiphoton fluorescence recovery after photobleaching (MP-FRAP) is a laser
      microscopy technique used to measure diffusion coefficients of macromolecules in
      biological systems. The three-dimensional resolution and superior depth
      penetration within scattering samples offered by MP-FRAP make it an important
      tool for investigating both in vitro and in vivo systems. However, biological
      systems frequently confine diffusion within solid barriers, and to date the
      effect of such barriers on the measurement of absolute diffusion coefficients via
      MP-FRAP has not been studied. We have used Monte Carlo simulations of diffusion
      and MP-FRAP to understand the effect of barriers of varying geometries and
      positions relative to the two-photon focal volume. Furthermore, we supply ranges
      of barrier positions within which MP-FRAP can confidently be employed to measure
      accurate diffusion coefficients. Finally, we produce two new MP-FRAP models that
      can produce accurate diffusion coefficients in the presence of a single plane
      boundary or parallel infinite plane boundaries positioned parallel to the optical
      axis, up to the resolution limit of the multiphoton laser scanning microscope.

PMID- 21728581
TI  - Direct determination of the refractive index of natural multilayer systems.
AB  - It is well known that the metal-like strong reflection observed in the elytra of
      some kinds of beetles is produced by multilayer thin-film interference. For the
      quantitative analyses of the structural colors in these elytra, it is necessary
      to know accurate values of the refractive indices of the materials that comprise
      the multilayer structure. However, index determination is not an easy task: The
      elytron surface is not flat but curved and usually contains many irregular bumps,
      which cause scattering loss. These structural characteristics prevent us from
      directly applying conventional optical techniques for index determination, such
      as ellipsometry, since these techniques require a perfectly specular surface. In
      this paper, we report a new experimental procedure that can directly determine
      the refractive indices of individual layers in natural multilayer systems. This
      procedure involves semi-frontal thin-sectioning of the sample and subsequent
      optical examinations using a microspectrophotometer. We demonstrate that the
      complex refractive index and its wavelength dependence can be successfully
      determined for one kind of beetle.

PMID- 21728582
TI  - Alternate measure of information useful for DNA sequences.
AB  - We propose an alternate measure of information, called superinformation, which
      has been found to be very effective for analyzing the coding and noncoding
      regions of the DNA. This superinformation is actually a measure of the
      "randomness of randomness." It has been found to be highly accurate in
      classifying coding and noncoding regions of human DNA. In the proposed method, no
      prior training is required. This technique exhibits higher accuracy than
      previously reported techniques in distinguishing between the coding and the
      noncoding portions of the DNA. Superinformation can also be used to analyze the
      untranslated regions in various genes.

PMID- 21728583
TI  - beta-Connectin studies by small-angle x-ray scattering and single-molecule force
      spectroscopy by atomic force microscopy.
AB  - The three-dimensional structure and the mechanical properties of a beta-connectin
      fragment from human cardiac muscle, belonging to the I band, from I(27) to I(34),
      were investigated by small-angle x-ray scattering (SAXS) and single-molecule
      force spectroscopy (SMFS). This molecule presents an entropic elasticity
      behavior, associated to globular domain unfolding, that has been widely studied
      in the last 10 years. In addition, atomic force microscopy based SMFS experiments
      suggest that this molecule has an additional elastic regime, for low forces,
      probably associated to tertiary structure remodeling. From a structural point of
      view, this behavior is a mark of the fact that the eight domains in the I(27)
      I(34) fragment are not independent and they organize in solution, assuming a well
      defined three-dimensional structure. This hypothesis has been confirmed by SAXS
      scattering, both on a diluted and a concentrated sample. Two different models
      were used to fit the SAXS curves: one assuming a globular shape and one
      corresponding to an elongated conformation, both coupled with a Coulomb repulsion
      potential to take into account the protein-protein interaction. Due to the
      predominance of the structure factor, the effective shape of the protein in
      solution could not be clearly disclosed. By performing SMFS by atomic force
      microscopy, mechanical unfolding properties were investigated. Typical sawtooth
      profiles were obtained and the rupture force of each unfolding domain was
      estimated. By fitting a wormlike chain model to each peak of the sawtooth
      profile, the entropic elasticity of octamer was described.

PMID- 21728584
TI  - Cytoskeleton fluidization versus resolidification: prestress effect.
AB  - The differential elastic modulus of an active actomyosin network is computed as a
      function of applied stress, taking into account both thermal and motor
      contributions to filament compliance in the low-frequency domain. It is shown
      that, due to a dual nature of motor activity, increasing motor concentration may
      either stiffen the network due to stronger prestress or soften it due to motor
      agitation, in accordance with experimental data. Prestress anisotropy, which may
      be induced by redistribution of motors triggered by external force, causes
      anisotropy of the elastic moduli. This helps to explain the contradictory
      phenomena of cell fluidization and resolidification in response to transient
      stretch observed in recent experiments.

PMID- 21728585
TI  - Interface-mediated interactions: entropic forces of curved membranes.
AB  - Particles embedded in a fluctuating interface experience forces and torques
      mediated by the deformations and by the thermal fluctuations of the medium.
      Considering a system of two cylinders bound to a fluid membrane, we show that the
      entropic contribution enhances the curvature-mediated repulsion between the two
      cylinders. This is contrary to the usual attractive Casimir force in the absence
      of curvature-mediated interactions. For a large distance between the cylinders,
      we retrieve the renormalization of the surface tension of a flat membrane due to
      thermal fluctuations.

PMID- 21728586
TI  - Corrected mean-field models for spatially dependent advection-diffusion-reaction
      phenomena.
AB  - In the exclusion-process literature, mean-field models are often derived by
      assuming that the occupancy status of lattice sites is independent. Although this
      assumption is questionable, it is the foundation of many mean-field models. In
      this work we develop methods to relax the independence assumption for a range of
      discrete exclusion-process-based mechanisms motivated by applications from cell
      biology. Previous investigations that focused on relaxing the independence
      assumption have been limited to studying initially uniform populations and
      ignored any spatial variations. By ignoring spatial variations these previous
      studies were greatly simplified due to translational invariance of the lattice.
      These previous corrected mean-field models could not be applied to many important
      problems in cell biology such as invasion waves of cells that are characterized
      by moving fronts. Here we propose generalized methods that relax the independence
      assumption for spatially inhomogeneous problems, leading to corrected mean-field
      descriptions of a range of exclusion-process-based models that incorporate (i)
      unbiased motility, (ii) biased motility, and (iii) unbiased motility with agent
      birth and death processes. The corrected mean-field models derived here are
      applicable to spatially variable processes including invasion wave-type problems.
      We show that there can be large deviations between simulation data and
      traditional mean-field models based on invoking the independence assumption.
      Furthermore, we show that the corrected mean-field models give an improved match
      to the simulation data in all cases considered.

PMID- 21728587
TI  - Coupled radial and longitudinal displacements and stresses within the arterial
      wall in pulsatile flow under tethered and free-wall conditions.
AB  - An analytical solution is presented of the governing equations for the coupled
      radial and longitudinal displacements and stresses within the finite thickness of
      the arterial wall in pulsatile flow. The results are used to examine the extent
      of coupling between the radial and longitudinal dynamics within the vessel wall,
      particularly when the wall is fully tethered. In the case of a free wall, it is
      found that the dynamics in the two directions are fairly decoupled from each
      other when the wavelength is at least of the order of 100 times the vessel
      radius. At 10 times the vessel radius, however, there is strong coupling between
      the two. These findings are consistent with expectations in the case of a free
      wall where the long-wave approximation has been applied in the past. In the case
      of a tethered wall, however, the results indicate that in general the long-wave
      approximation is strictly valid only when the combination of wall material and
      tethering allow the wave to be long.

PMID- 21728588
TI  - Force generation in bacteria without nucleotide-dependent bending of cytoskeletal
      filaments.
AB  - Binary cell division in bacteria occurs via the formation and subsequent
      contraction of a polymeric ring, the so-called Z ring, at the middle of the cell.
      This ring is made of filamenting temperature-sensitive Z (FtsZ) proteins and it
      shrinks in radius to generate a contractile radial force on the cell membrane.
      Although a few models have been proposed, the ring contraction mechanism still
      remains a mystery. The models rely on various physical properties of the FtsZ
      filaments, some of which have been verified through in vitro experiments and some
      of which remain unclear. A feature common to all these models is the hydrolysis
      driven transition of FtsZ filaments from straight to curved conformations. While
      the intrinsic curvature of FtsZ filaments has been experimentally established
      beyond doubt, evidence has been mounting against the existence of any transition
      between the straight FtsZ-GTP and the curved FtsZ-GDP conformations. Preliminary
      results from our earlier work [B. Ghosh and A. Sain, Phys. Rev. Lett. 101, 178101
      (2008)] indicated that hydrolysis-induced bending is not necessary for Z-ring
      contraction. Since then many new experimental observations have been reported on
      this subject and in view of these here we argue that our model appears even more
      plausible than before. In addition, we have explored more realistic features,
      such as how the length distribution of FtsZ filaments in the cytoplasm may
      influence the contraction dynamics, and we have also demonstrated that the Z ring
      retains approximately the same number of monomers, although not the same
      monomers, during the course of contraction as reported by fluorescence
      experiments.

PMID- 21728589
TI  - Measurement of the nonlinear elasticity of red blood cell membranes.
AB  - The membranes of human red blood cells (RBCs) are a composite of a fluid lipid
      bilayer and a triangular network of semiflexible filaments (spectrin). We perform
      cellular microrheology using the dynamic membrane fluctuations of the RBCs to
      extract the elastic moduli of this composite membrane. By applying known osmotic
      stresses, we measure the changes in the elastic constants under imposed strain
      and thereby determine the nonlinear elastic properties of the membrane. We find
      that the elastic nonlinearities of the shear modulus in tensed RBC membranes can
      be well understood in terms of a simple wormlike chain model. Our results show
      that the elasticity of the spectrin network can mostly account for the area
      compression modulus at physiological osmolality, suggesting that the lipid
      bilayer has significant excess area. As the cell swells, the elastic contribution
      from the now tensed lipid membrane becomes dominant.

PMID- 21728590
TI  - Charge density and bending rigidity of a rodlike polyelectrolyte: effects of
      multivalent counterions.
AB  - We study line charge density and bending persistence length of a semiflexible
      polyelectrolyte rod typified by DNA in a z:1 electrolyte with or without pre
      existing 1:1 salt. We use a wormlike chain model, where the effective Hamiltonian
      incorporates bending energy, as well as where the Coulomb interaction between
      charged segments is screened and mediated by the ions in the solution. By
      analytically evaluating the free energy associated with the contour undulation
      and charge density fluctuation affected by the adsorbed ions, we find
      renormalized mean line-charge-density and persistence length. Multivalent
      counterions bind to the polyelectrolyte more readily than monovalent counterions,
      due to electrostatic attraction dominant over the entropy. Also, our results show
      that at physiological conditions the electrostatic interaction gives no
      appreciable change on the persistence length from its bare value, against the
      implications of earlier studies. This is because the mean-field and charge
      fluctuation effects largely cancel each other in the rodlike conformation.

PMID- 21728591
TI  - Approaching the ground states of the random maximum two-satisfiability problem by
      a greedy single-spin flipping process.
AB  - In this brief report we explore the energy landscapes of two spin glass models
      using a greedy single-spin flipping process, Gmax. The ground-state energy
      density of the random maximum two-satisfiability problem is efficiently
      approached by Gmax. The achieved energy density e(t) decreases with the evolution
      time t as e(t)-e(infinity)=h(log(10)t)(-z) with a small prefactor h and a scaling
      coefficient z>1, indicating an energy landscape with deep and rugged funnel-shape
      regions. For the +/-J Viana-Bray spin glass model, however, the greedy single
      spin dynamics quickly gets trapped to a local minimal region of the energy
      landscape.

PMID- 21728592
TI  - Double negative differential thermal resistance induced by nonlinear on-site
      potentials.
AB  - We study heat conduction through one-dimensional homogeneous lattices in the
      presence of the nonlinear on-site potentials containing the bounded and unbounded
      parts, and the harmonic interaction potential. We observe the occurrence of
      double negative differential thermal resistance (NDTR); namely, there exist two
      regions of temperature difference, where the heat flux decreases as the applied
      temperature difference increases. The nonlinearity of the bounded part
      contributes to NDTR at low temperatures and NDTR at high temperatures is induced
      by the nonlinearity of the unbounded part. The nonlinearity of the on-site
      potentials is necessary to obtain NDTR for the harmonic interaction homogeneous
      lattices. However, for the anharmonic homogeneous lattices, NDTR even occurs in
      the absence of the on-site potentials, for example, the rotator model.

PMID- 21728593
TI  - Scaling behaviors of the voltage distribution in dielectric breakdown networks.
AB  - We study the distribution of voltage drops across bonds in dielectric breakdown
      networks and its qth moments in the two-dimensional Euclidean space. Performing
      numerical simulations, we find that the distribution is composed of three
      different power-law regimes which are distinguished by two crossover voltages
      V(1) and V(2). The scaling behaviors of these crossover voltages with respect to
      the system size govern those of the qth moments of the voltage distribution. This
      feature differs from the multifractal behavior of the qth moment in random
      resistor networks. We discuss the implications of these scaling behaviors in
      relation to the application of the dielectric breakdown network to memory
      devices.

PMID- 21728594
TI  - Energy-transfer process in gas models of Lennard-Jones interactions.
AB  - We perform simulations to investigate how the energy carried by a molecule
      transfers to others in an equilibrium gas model. For this purpose we consider a
      microcanonical ensemble of equilibrium gas systems; each of them contains a
      tagged molecule located at the same position initially. The ensuing transfer
      process of the energy initially carried by the tagged molecule is then exposed in
      terms of the ensemble-averaged energy density distribution. In both a two- and a
      three-dimensional gas model with Lennard-Jones interactions at room temperature,
      it is found that the energy carried by a molecule propagates in the gas
      ballistically, in clear contrast with the Gaussian diffusion widely assumed in
      previous studies. A possible scheme of experimental study of this issue is also
      proposed.

PMID- 21728595
TI  - Generalized Eden model with a screening effect.
AB  - We generalize the Eden model to take into account the screening effect, i.e., the
      end point grows much faster than the interior points do. Highly anisotropic
      clusters are obtained in our generalized Eden model. It is found that the length
      in the long direction scales differently than that in the short direction does as
      the number of sites increases.

PMID- 21728596
TI  - Subdiffusion on a fractal comb.
AB  - Subdiffusion on a fractal comb is considered. A mechanism of subdiffusion with a
      transport exponent different from 1/2 is suggested. It is shown that the
      transport exponent is determined by the fractal geometry of the comb.

PMID- 21728597
TI  - Chemotaxis can provide biological organisms with good solutions to the travelling
      salesman problem.
AB  - The ability to find good solutions to the traveling salesman problem can benefit
      some biological organisms. Bacterial infection would, for instance, be eradicated
      most promptly if cells of the immune system minimized the total distance they
      traveled when moving between bacteria. Similarly, foragers would maximize their
      net energy gain if the distance that they traveled between multiple dispersed
      prey items was minimized. The traveling salesman problem is one of the most
      intensively studied problems in combinatorial optimization. There are no
      efficient algorithms for even solving the problem approximately (within a
      guaranteed constant factor from the optimum) because the problem is
      nondeterministic polynomial time complete. The best approximate algorithms can
      typically find solutions within 1%-2% of the optimal, but these are
      computationally intensive and can not be implemented by biological organisms.
      Biological organisms could, in principle, implement the less efficient greedy
      nearest-neighbor algorithm, i.e., always move to the nearest surviving target.
      Implementation of this strategy does, however, require quite sophisticated
      cognitive abilities and prior knowledge of the target locations. Here, with the
      aid of numerical simulations, it is shown that biological organisms can simply
      use chemotaxis to solve, or at worst provide good solutions (comparable to those
      found by the greedy algorithm) to, the traveling salesman problem when the
      targets are sources of a chemoattractant and are modest in number (n < 10). This
      applies to neutrophils and macrophages in microbial defense and to some
      predators.

PMID- 21728598
TI  - Observation of the stabilizing effect of a laminated ablator on the ablative
      Rayleigh-Taylor instability.
AB  - A laminated ablator is explored as an alternative concept for stabilizing the
      ablative Rayleigh-Taylor instability which develops in inertial fusion targets.
      Experiments measuring the growth of the Rayleigh-Taylor instability of laminated
      planar foils are reported. Consistent with both theory and simulations, a
      significant reduction of the perturbation growth is experimentally observed for
      laminated ablators in comparison to what is observed for classical uniform
      ablators. Such an enhanced hydrodynamic stability opens opportunities for the
      design of high-gain inertial fusion targets.

PMID- 21728599
TI  - Quantification of deviations from rationality with heavy tails in human dynamics.
AB  - The dynamics of technological, economic and social phenomena is controlled by how
      humans organize their daily tasks in response to both endogenous and exogenous
      stimulations. Queueing theory is believed to provide a generic answer to account
      for the often observed power-law distributions of waiting times before a task is
      fulfilled. However, the general validity of the power law and the nature of other
      regimes remain unsettled. Using anonymized data collected by Google at the World
      Wide Web level, we identify the existence of several additional regimes
      characterizing the time required for a population of Internet users to execute a
      given task after receiving a message. Depending on the under- or over-utilization
      of time by the population of users and the strength of their response to
      perturbations, the pure power law is found to be coextensive with an exponential
      regime (tasks are performed without too much delay) and with a crossover to an
      asymptotic plateau (some tasks are never performed).

PMID- 21728600
TI  - Theory of volumetric capacitance of an electric double-layer supercapacitor.
AB  - Electric double-layer supercapacitors are a fast-rising class of high-power
      energy storage devices based on porous electrodes immersed in a concentrated
      electrolyte or ionic liquid. As yet there is no microscopic theory to describe
      their surprisingly large capacitance per unit volume (volumetric capacitance) of
      ~100 F/cm(3), nor is there a good understanding of the fundamental limits on
      volumetric capacitance. In this paper we present a non-mean-field theory of the
      volumetric capacitance of a supercapacitor that captures the discrete nature of
      the ions and the exponential screening of their repulsive interaction by the
      electrode. We consider analytically and via Monte Carlo simulations the case of
      an electrode made from a good metal and show that in this case the volumetric
      capacitance can reach the record values. We also study how the capacitance is
      reduced when the electrode is an imperfect metal characterized by some finite
      screening radius. Finally, we argue that a carbon electrode, despite its
      relatively large linear screening radius, can be approximated as a perfect metal
      because of its strong nonlinear screening. In this way the experimentally
      measured capacitance values of ~100 F/cm(3) may be understood.

PMID- 21728601
TI  - Selective advantage of tolerant cultural traits in the Axelrod-Schelling model.
AB  - The Axelrod-Schelling model incorporates into the original Axelrod's model of
      cultural dissemination the possibility that cultural agents placed in culturally
      dissimilar environments move to other places, the strength of this mobility being
      controlled by an intolerance parameter. By allowing heterogeneity in the
      intolerance of cultural agents, and considering it as a cultural feature, i.e.,
      susceptible of cultural transmission (thus breaking the original symmetry of
      Axelrod-Schelling dynamics), we address here the question of whether tolerant or
      intolerant traits are more likely to become dominant in the long-term cultural
      dynamics. Our results show that tolerant traits possess a clear selective
      advantage in the framework of the Axelrod-Schelling model. We show that the
      reason for this selective advantage is the development, as time evolves, of a
      positive correlation between the number of neighbors that an agent has in its
      environment and its tolerant character.

PMID- 21728602
TI  - Unified framework for quasispecies evolution and stochastic quantization.
AB  - In this paper we provide a unified framework for quasispecies evolution and
      stochastic quantization. We map the biological evolution described by the
      quasispecies equation to the stochastic dynamics of an ensemble of particles
      undergoing a creation-annihilation process. We show that this mapping identifies
      a natural decomposition of the probability that an individual has a certain
      genotype into eigenfunctions of the evolutionary operator. This alternative
      approach to study the quasispecies equation allows for a generalization of the
      Fisher theorem equivalent to the Price equation. According to this relation the
      average fitness of an asexual population increases with time proportional to the
      variance of the eigenvalues of the evolutionary operator. Moreover, from the
      present alternative formulation of stochastic quantization a novel scenario
      emerges to be compared with existing approaches. The evolution of an ensemble of
      particles undergoing diffusion and a creation-annihilation process is
      parametrized by a variable beta that we call the inverse temperature of the
      stochastic dynamics. We find that the evolution equation at high temperatures is
      simply related to the Schrodinger equation, but at low temperature it strongly
      deviates from it. In the presence of additional noise in scattering processes
      between the particles, the evolution reaches a steady state described by the Bose
      Einstein statistics.

PMID- 21728603
TI  - Locally optimal heuristic for modularity maximization of networks.
AB  - Community detection in networks based on modularity maximization is currently
      done with hierarchical divisive or agglomerative as well as partitioning
      heuristics, hybrids, and, in a few papers, exact algorithms. We consider here the
      case of hierarchical networks in which communities should be detected and propose
      a divisive heuristic which is locally optimal in the sense that each of the
      successive bipartitions is done in a provably optimal way. This heuristic is
      compared with the spectral-based hierarchical divisive heuristic of Newman [Proc.
      Natl. Acad. Sci. USA 103, 8577 (2006).] and with the hierarchical agglomerative
      heuristic of Clauset, Newman, and Moore [Phys. Rev. E 70, 066111 (2004).].
      Computational results are given for a series of problems of the literature with
      up to 4941 vertices and 6594 edges. They show that the proposed divisive
      heuristic gives better results than the divisive heuristic of Newman and than the
      agglomerative heuristic of Clauset et al.

PMID- 21728604
TI  - Keyword extraction by nonextensivity measure.
AB  - The presence of a long-range correlation in the spatial distribution of a
      relevant word type, in spite of random occurrences of an irrelevant word type, is
      an important feature of human-written texts. We classify the correlation between
      the occurrences of words by nonextensive statistical mechanics for the word
      ranking process. In particular, we look at the nonextensivity parameter as an
      alternative metric to measure the spatial correlation in the text, from which the
      words may be ranked in terms of this measure. Finally, we compare different
      methods for keyword extraction.

PMID- 21728605
TI  - Cascades on a class of clustered random networks.
AB  - We present an analytical approach to determining the expected cascade size in a
      broad range of dynamical models on the class of random networks with arbitrary
      degree distribution and nonzero clustering introduced previously in [M. E. J.
      Newman, Phys. Rev. Lett. 103, 058701 (2009)]. A condition for the existence of
      global cascades is derived as well as a general criterion that determines whether
      increasing the level of clustering will increase, or decrease, the expected
      cascade size. Applications, examples of which are provided, include site
      percolation, bond percolation, and Watts' threshold model; in all cases
      analytical results give excellent agreement with numerical simulations.

PMID- 21728606
TI  - Scaling mobility patterns and collective movements: deterministic walks in
      lattices.
AB  - Scaling mobility patterns have been widely observed for animals. In this paper,
      we propose a deterministic walk model to understand the scaling mobility
      patterns, where walkers take the least-action walks on a lattice landscape and
      prey. Scaling laws in the displacement distribution emerge when the amount of
      prey resource approaches the critical point. Around the critical point, our model
      generates ordered collective movements of walkers with a quasiperiodic
      synchronization of walkers' directions. These results indicate that the
      coevolution of walkers' least-action behavior and the landscape could be a
      potential origin of not only the individual scaling mobility patterns but also
      the flocks of animals. Our findings provide a bridge to connect the individual
      scaling mobility patterns and the ordered collective movements.

PMID- 21728607
TI  - Social network dynamics of face-to-face interactions.
AB  - The recent availability of data describing social networks is changing our
      understanding of the "microscopic structure" of a social tie. A social tie indeed
      is an aggregated outcome of many social interactions such as face-to-face
      conversations or phone calls. Analysis of data on face-to-face interactions shows
      that such events, as many other human activities, are bursty, with very
      heterogeneous durations. In this paper we present a model for social interactions
      at short time scales, aimed at describing contexts such as conference venues in
      which individuals interact in small groups. We present a detailed analytical and
      numerical study of the model's dynamical properties, and show that it reproduces
      important features of empirical data. The model allows for many generalizations
      toward an increasingly realistic description of social interactions. In
      particular, in this paper we investigate the case where the agents have intrinsic
      heterogeneities in their social behavior, or where dynamic variations of the
      local number of individuals are included. Finally we propose this model as a very
      flexible framework to investigate how dynamical processes unfold in social
      networks.

PMID- 21728608
TI  - Opinion dynamics of random-walking agents on a lattice.
AB  - The opinion dynamics of random-walking agents on finite two-dimensional lattices
      is studied. In the model, the opinion is continuous, and both the lattice and the
      opinion can be either periodic or nonperiodic. At each time step, all agents move
      randomly on the lattice, and update their opinions based on those of neighbors
      with whom the differences of opinion are not greater than a given threshold. Due
      to the effect of repeated averaging, opinions first converge locally, and
      eventually reach steady states. As in other models with bounded confidence,
      steady states in general are those with one or more opinion groups in which all
      agents have the same opinion. When both the lattice and the opinion are periodic,
      however, metastable states can emerge, in which the whole spectrum of location
      dependent opinions can coexist. This result shows that, when a set of continuous
      opinions forms a structure like a circle, unlike the typically used linear
      opinions, rich dynamic behavior can arise. When there are geographical
      restrictions in real situations, a complete consensus is rarely reached, and
      metastable states here might be one of the explanations for these situations,
      especially when opinions are not linear.

PMID- 21728609
TI  - Dynamics and complexity of the Schelling segregation model.
AB  - In this paper we consider the Schelling social segregation model for two
      different populations. In Schelling's model, segregation appears as a consequence
      of discrimination, measured by the local difference between two populations. For
      that, the model defines a tolerance criterion on the neighborhood of an
      individual, indicating wether the individual is able to move to a new place or
      not. Next, the model chooses which of the available unhappy individuals really
      moves. In our work, we study the patterns generated by the dynamical evolution of
      the Schelling model in terms of various parameters or the initial condition, such
      as the size of the neighborhood of an inhabitant, the tolerance, and the initial
      number of individuals. As a general rule we observe that segregation patterns
      minimize the interface of zones of different people. In this context we introduce
      an energy functional associated with the configuration which is a strictly
      decreasing function for the tolerant people case. Moreover, as far as we know, we
      are the first to notice that in the case of a non-strictly-decreasing energy
      functional, the system may segregate very efficiently.

PMID- 21728610
TI  - Path integral approach to the pricing of timer options with the Duru-Kleinert
      time transformation.
AB  - In this paper, a time substitution as used by Duru and Kleinert in their
      treatment of the hydrogen atom with path integrals is performed to price timer
      options under stochastic volatility models. We present general pricing formulas
      for both the perpetual timer call options and the finite time-horizon timer call
      options. These general results allow us to find closed-form pricing formulas for
      both the perpetual and the finite time-horizon timer options under the 3/2
      stochastic volatility model as well as under the Heston stochastic volatility
      model. For the treatment of timer options under the 3/2 model we will rely on the
      path integral for the Morse potential, with the Heston model we will rely on the
      Kratzer potential.

PMID- 21728611
TI  - Structural and functional networks in complex systems with delay.
AB  - Functional networks of complex systems are obtained from the analysis of the
      temporal activity of their components, and are often used to infer their unknown
      underlying connectivity. We obtain the equations relating topology and function
      in a system of diffusively delay-coupled elements in complex networks. We solve
      exactly the resulting equations in motifs (directed structures of three nodes)
      and in directed networks. The mean-field solution for directed uncorrelated
      networks shows that the clusterization of the activity is dominated by the in
      degree of the nodes, and that the locking frequency decreases with increasing
      average degree. We find that the exponent of a power law degree distribution of
      the structural topology gamma is related to the exponent of the associated
      functional network as alpha=(2-gamma)(-1) for gamma<2.

PMID- 21728612
TI  - Inference and learning in sparse systems with multiple states.
AB  - We discuss how inference can be performed when data are sampled from the
      nonergodic phase of systems with multiple attractors. We take as a model system
      the finite connectivity Hopfield model in the memory phase and suggest a cavity
      method approach to reconstruct the couplings when the data are separately sampled
      from few attractor states. We also show how the inference results can be
      converted into a learning protocol for neural networks in which patterns are
      presented through weak external fields. The protocol is simple and fully local,
      and is able to store patterns with a finite overlap with the input patterns
      without ever reaching a spin-glass phase where all memories are lost.

PMID- 21728613
TI  - Optimal topology for parallel discrete-event simulations.
AB  - The effect of shortcuts on the task completion landscape in parallel discrete
      event simulation (PDES) is investigated. The morphology of the task completion
      landscape in PDES is known to be described well by the Langevin-type equation for
      nonequillibrium interface growth phenomena, such as the Kardar-Parisi-Zhang
      equation. From the numerical simulations, we find that the root-mean-squared
      fluctuation of task completion landscape, W(t,N), scales as W(t->infinity,N)~N
      when the number of shortcuts, l, is finite. Here N is the number of nodes. This
      behavior can be understood from the mean-field type argument with effective
      defects when l is finite. We also study the behavior of W(t,N) when l increases
      as N increases and provide a criterion to design an optimal topology to achieve a
      better synchronizability in PDES.

PMID- 21728614
TI  - Grain reconstruction of porous media: application to a Bentheim sandstone.
AB  - The two-point correlation measured on a thin section can be used to derive the
      probability density of the radii of a population of penetrable spheres. The
      geometrical, transport, and deformation properties of samples derived by this
      method compare well with the properties of the digitized real sample and of the
      samples generated by the standard grain reconstruction method.

PMID- 21728615
TI  - Continuous-space automaton model for pedestrian dynamics.
AB  - An off-lattice automaton for modeling pedestrian dynamics is presented.
      Pedestrians are represented by disks with variable radius that evolve following
      predefined rules. The key feature of our approach is that although positions and
      velocities are continuous, forces do not need to be calculated. This has the
      advantage that it allows using a larger time step than in force-based models. The
      room evacuation problem and circular racetrack simulations quantitatively
      reproduce the available experimental data, both for the specific flow rate and
      for the fundamental diagram of pedestrian traffic with an outstanding
      performance. In this last case, the variation of two free parameters (r(min) and
      r(max)) of the model accounts for the great variety of experimental fundamental
      diagrams reported in the literature. Moreover, this variety can be interpreted in
      terms of these model parameters.

PMID- 21728616
TI  - Radical-ion-pair reactions are the biochemical equivalent of the optical double
      slit experiment.
AB  - Radical-ion-pair reactions were recently shown to represent a rich biophysical
      laboratory for the application of quantum measurement theory methods and
      concepts. Here we show that radical-ion-pair reactions essentially form a
      nonlinear biochemical double-slit interferometer. Quantum coherence effects are
      visible when "which-path" information is limited, and the incoherent limit is
      approached when measurement-induced decoherence sets in. Based on this analogy
      with the optical double-slit experiment we derive and elaborate on the
      fundamental master equation of spin-selective radical-ion-pair reactions that
      covers the continuous range from complete incoherence to maximum singlet-triplet
      coherence.

PMID- 21728617
TI  - Tolerating the community detection resolution limit with edge weighting.
AB  - Communities of vertices within a giant network such as the World Wide Web are
      likely to be vastly smaller than the network itself. However, Fortunato and
      Barthelemy have proved that modularity maximization algorithms for community
      detection may fail to resolve communities with fewer than ?L/2 edges, where L is
      the number of edges in the entire network. This resolution limit leads modularity
      maximization algorithms to have notoriously poor accuracy on many real networks.
      Fortunato and Barthelemy's argument can be extended to networks with weighted
      edges as well, and we derive this corollary argument. We conclude that weighted
      modularity algorithms may fail to resolve communities with less than ?Wepsilon/2
      total edge weight, where W is the total edge weight in the network and epsilon is
      the maximum weight of an intercommunity edge. If epsilon is small, then small
      communities can be resolved. Given a weighted or unweighted network, we describe
      how to derive new edge weights in order to achieve a low epsilon, we modify the
      Clauset, Newman, and Moore (CNM) community detection algorithm to maximize
      weighted modularity, and we show that the resulting algorithm has greatly
      improved accuracy. In experiments with an emerging community standard benchmark,
      we find that our simple CNM variant is competitive with the most accurate
      community detection methods yet proposed.

PMID- 21728618
TI  - Mechanics of three-dimensional, nonbonded random fiber networks.
AB  - The mechanical behavior of an ensemble of athermal fibers forming a nonbonded
      network subjected to triaxial compression is studied using a numerical model. The
      response exhibits a power law dependence of stress on the dilatation strain and
      hysteresis upon loading and unloading. A stable hysteresis loop results after the
      first loading and unloading cycle. In the early stages of compaction, strain
      energy is associated primarily with the bending of fibers, while at higher
      densities, it is stored primarily in the axial deformation mode. It is shown that
      the exponent of the power law, and the partition of energy in the axial and
      bending modes depends on the ratio of the bending to axial stiffness of the
      fibers. Accounting for interfiber friction does not change the functional form of
      the stress-strain relationship or the exponent. The central feature that
      distinguishes the mechanics of this system from that of bonded random networks is
      the relative sliding at contacts and the ensuing fiber rearrangements. We show
      that suppressing sliding leads to a much stiffer response. The results indicate
      that the value of the exponent of the stress-strain power law is determined not
      only by fiber bending and the formation of new contacts, but also by the relative
      sliding and axial deformation of fibers.

PMID- 21728619
TI  - Multiple epidemic waves in delayed susceptible-infected-recovered models on
      complex networks.
AB  - We consider a delayed susceptible-infected-recovered epidemic model on an
      uncorrelated complex network and address the effect of time lag on the shape and
      multiple waves of epidemic curves. We show that when the transmission rate is
      above a threshold, a large delay can cause multiple waves with larger amplitudes
      in the second and subsequent waves.

PMID- 21728620
TI  - Direct, physically motivated derivation of the contagion condition for spreading
      processes on generalized random networks.
AB  - For a broad range of single-seed contagion processes acting on generalized random
      networks, we derive a unifying analytic expression for the possibility of global
      spreading events in a straightforward, physically intuitive fashion. Our
      reasoning lays bare a direct mechanical understanding of an archetypal spreading
      phenomena that is not evident in circuitous extant mathematical approaches.

PMID- 21728621
TI  - Coarse graining for synchronization in directed networks.
AB  - Coarse-graining model is a promising way to analyze and visualize large-scale
      networks. The coarse-grained networks are required to preserve statistical
      properties as well as the dynamic behaviors of the initial networks. Some methods
      have been proposed and found effective in undirected networks, while the study on
      coarse-graining directed networks lacks of consideration. In this paper we
      proposed a path-based coarse-graining (PCG) method to coarse grain the directed
      networks. Performing the linear stability analysis of synchronization and
      numerical simulation of the Kuramoto model on four kinds of directed networks,
      including tree networks and variants of Barabasi-Albert networks, Watts-Strogatz
      networks, and Erdos-Renyi networks, we find our method can effectively preserve
      the network synchronizability.

PMID- 21728622
TI  - Vertical cultural transmission effects on demic front propagation: theory and
      application to the Neolithic transition in Europe.
AB  - It is shown that Lotka-Volterra interaction terms are not appropriate to describe
      vertical cultural transmission. Appropriate interaction terms are derived and
      used to compute the effect of vertical cultural transmission on demic front
      propagation. They are also applied to a specific example, the Neolithic
      transition in Europe. In this example, it is found that the effect of vertical
      cultural transmission can be important (about 30%). On the other hand, simple
      models based on differential equations can lead to large errors (above 50%).
      Further physical, biophysical, and cross-disciplinary applications are outlined.

PMID- 21728623
TI  - Communities and beyond: mesoscopic analysis of a large social network with
      complementary methods.
AB  - Community detection methods have so far been tested mostly on small empirical
      networks and on synthetic benchmarks. Much less is known about their performance
      on large real-world networks, which nonetheless are a significant target for
      application. We analyze the performance of three state-of-the-art community
      detection methods by using them to identify communities in a large social network
      constructed from mobile phone call records. We find that all methods detect
      communities that are meaningful in some respects but fall short in others, and
      that there often is a hierarchical relationship between communities detected by
      different methods. Our results suggest that community detection methods could be
      useful in studying the general mesoscale structure of networks, as opposed to
      only trying to identify dense structures.

PMID- 21728624
TI  - Intrinsic stickiness and chaos in open integrable billiards: tiny border effects.
AB  - Rounding border effects at the escape point of open integrable billiards are
      analyzed via the escape-time statistics and emission angles. The model is the
      rectangular billiard and the shape of the escape point is assumed to have a
      semicircular form. Stickiness, chaos, and self-similar structures for the escape
      times and emission angles are generated inside "backgammon" like stripes of
      initial conditions. These stripes are born at the boundary between two different
      emission angles but with the same escape times and when rounding effects increase
      they start to overlap generating a very rich dynamics. Tiny rounded borders
      (around 0.1% from the whole billiard size) are shown to be sufficient to generate
      the sticky motion with power-law decay gamma(esc)=1.27, while borders larger than
      10% are enough to produce escape times related to the chaotic motion. Escape
      exponents in the interval 1<gamma(esc)<2 are generated due to marginal unstable
      periodic orbits trapping alternately (in time) regular and chaotic trajectories.

PMID- 21728625
TI  - Quantum entanglement between a nonlinear nanomechanical resonator and a microwave
      field.
AB  - We consider a theoretical model for a nonlinear nanomechanical resonator coupled
      to a superconducting microwave resonator. The nanomechanical resonator is driven
      parametrically at twice its resonance frequency, while the superconducting
      microwave resonator is driven with two tones that differ in frequency by an
      amount equal to the parametric driving frequency. We show that the semiclassical
      approximation of this system has an interesting fixed-point bifurcation
      structure. In the semiclassical dynamics a transition from stable fixed points to
      limit cycles is observed as one moves from positive to negative detuning. We show
      that signatures of this bifurcation structure are also present in the full
      dissipative quantum system and further show that the bifurcation structure leads
      to mixed-state entanglement between the nanomechanical resonator and the
      microwave cavity in the dissipative quantum system that is a maximum close to the
      semiclassical bifurcation. Quantum signatures of the semiclassical limit cycles
      are presented.

PMID- 21728626
TI  - Chaotic saddles in a gravitational field: the case of inertial particles in
      finite domains.
AB  - The motion of inertial particles is investigated numerically in a time-periodic
      flow in the presence of gravity. The flow is restricted to a finite (or semi
      infinite) vertical column, and the dynamics is therefore transiently chaotic. The
      long-term motion of the center of mass is a uniform settling. The settling
      velocity is found to differ from the one that would characterize a still fluid,
      and the distribution of an ensemble of settling particles spreads with a well
      defined diffusion coefficient. The underlying chaotic saddle appears to have a
      height-dependent fractal dimension. The coarse-grained density of both the
      natural measure and the conditionally invariant measure (defined along the
      unstable manifold) of the saddle is smooth, and exhibits a local maximum as a
      function of the height. The latter density corresponds to the eigenfunction of
      the first eigenvalue of an effective Fokker-Planck equation subject to an
      absorbing boundary condition at the bottom. The transport coefficients can be
      determined as averages taken with respect to the conditionally invariant measure.

PMID- 21728627
TI  - Pattern formation in oscillatory complex networks consisting of excitable nodes.
AB  - Oscillatory dynamics of complex networks has recently attracted great attention.
      In this paper we study pattern formation in oscillatory complex networks
      consisting of excitable nodes. We find that there exist a few center nodes and
      small skeletons for most oscillations. Complicated and seemingly random
      oscillatory patterns can be viewed as well-organized target waves propagating
      from center nodes along the shortest paths, and the shortest loops passing
      through both the center nodes and their driver nodes play the role of oscillation
      sources. Analyzing simple skeletons we are able to understand and predict various
      essential properties of the oscillations and effectively modulate the
      oscillations. These methods and results will give insights into pattern formation
      in complex networks and provide suggestive ideas for studying and controlling
      oscillations in neural networks.

PMID- 21728628
TI  - Wave packet dynamics in one-dimensional linear and nonlinear generalized
      Fibonacci lattices.
AB  - The spreading of an initially localized wave packet in one-dimensional linear and
      nonlinear generalized Fibonacci (GF) lattices is studied numerically. The GF
      lattices can be classified into two classes depending on whether or not the
      lattice possesses the Pisot-Vijayaraghavan property. For linear GF lattices of
      the first class, both the second moment and the participation number grow with
      time. For linear GF lattices of the second class, in the regime of a weak on-site
      potential, wave packet spreading is close to ballistic diffusion, whereas in the
      regime of a strong on-site potential, it displays stairlike growth in both the
      second moment and the participation number. Nonlinear GF lattices are then
      investigated in parallel. For the first class of nonlinear GF lattices, the
      second moment of the wave packet still grows with time, but the corresponding
      participation number does not grow simultaneously. For the second class of
      nonlinear GF lattices, an analogous phenomenon is observed for the weak on-site
      potential only. For a strong on-site potential that leads to an enhanced
      nonlinear self-trapping effect, neither the second moment nor the participation
      number grows with time. The results can be useful in guiding experiments on the
      expansion of noninteracting or interacting cold atoms in quasiperiodic optical
      lattices.

PMID- 21728629
TI  - Extreme multistability in a chemical model system.
AB  - Coupled systems can exhibit an unusual kind of multistability, namely, the
      coexistence of infinitely many attractors for a given set of parameters. This
      extreme multistability is demonstrated to occur in coupled chemical model systems
      with various types of coupling. We show that the appearance of extreme
      multistability is associated with the emergence of a conserved quantity in the
      long-term limit. This conserved quantity leads to a "slicing" of the state space
      into manifolds corresponding to the value of the conserved quantity. The state
      space "slices" develop as t->infinity and there exists at least one attractor in
      each of them. We discuss the dependence of extreme multistability on the coupling
      and on the mismatch of parameters of the coupled systems.

PMID- 21728630
TI  - Chaotic motion of propagating pulses in the Gray-Scott model.
AB  - Transition routes of propagating pulses in the Gray-Scott model from oscillatory
      to chaotic motion are investigated by numerical studies. Global bifurcation of
      the Gray-Scott model gives us information about the onset mechanism of transient
      dynamics, such as the splitting and extinction of pulses. However, the
      instability mechanism of oscillatory pulses has not been clarified, even
      numerically. Global bifurcation analysis of time periodic oscillatory traveling
      pulses, called traveling breathers, enables us to find chaotic motions of
      oscillatory pulse solutions. Two types of transitions to chaos, namely, period
      doubling sequences and breakdown of quasiperiodic solutions, are found near the
      bifurcation points of traveling breathers.

PMID- 21728631
TI  - Robustness of multilayer oscillator networks.
AB  - We consider the robustness of multilayer networks composed of active and inactive
      oscillators from the viewpoint of interlayer coupling effects through the aging
      transition [H. Daido and K. Nakanishi, Phys. Rev. Lett. 93, 104101 (2004)]. We
      show in detail that two-layer networks increase or decrease their robustness
      depending on interlayer coupling schemes compared with single-layer networks. In
      addition, we find that an increase of mismatches of oscillator types (active or
      inactive) among interlayer-connected oscillators reduces the robustness of the
      networks with mean-field, chain, and diffusive interlayer couplings in two-layer
      networks. Moreover, we discuss the robustness of networks with more than two
      layers.

PMID- 21728632
TI  - Order parameter for bursting polyrhythms in multifunctional central pattern
      generators.
AB  - We examine multistability of several coexisting bursting patterns in a central
      pattern generator network composed of three Hodgkin-Huxley type cells coupled
      reciprocally by inhibitory synapses. We establish that the control of switching
      between bursting polyrhythms and their bifurcations are determined by the
      temporal characteristics, such as the duty cycle, of networked interneurons and
      the coupling strength asymmetry. A computationally effective approach to the
      reduction of dynamics of the nine-dimensional network to two-dimensional Poincare
      return mappings for phase lags between the interneurons is presented.

PMID- 21728633
TI  - Nonmonotonic short-time decay of the Loschmidt echo in quasi-one-dimensional
      systems.
AB  - We study the short-time stability of quantum dynamics in quasi-one-dimensional
      systems with respect to small localized perturbations of the potential. To this
      end, we analytically and numerically address the decay of the Loschmidt echo (LE)
      during times that are short compared to the Ehrenfest time. We find that the LE
      is generally a nonmonotonic function of time and exhibits strongly pronounced
      minima and maxima at the instants when the corresponding classical particle
      traverses the perturbation region. We also show that, under general conditions,
      the envelope decay of the LE is well approximated by a Gaussian, and we derive
      explicit analytical formulas for the corresponding decay time. Finally, we
      demonstrate that the observed nonmonotonic nature of the LE decay is only
      pertinent to one-dimensional (and, more generally, quasi-one-dimensional)
      systems, and that the short-time decay of the LE can be monotonic in a higher
      number of dimensions.

PMID- 21728634
TI  - Mismatch and synchronization: influence of asymmetries in systems of two delay
      coupled lasers.
AB  - We study the synchronization properties of the delay dynamics of two identical
      semiconductor lasers coupled through a semitransparent mirror. Via an analytical
      and numerical approach, we investigate the influence of asymmetries, in
      particular mismatches of self- and cross-coupling strength and differences in
      self- and cross-coupling delay. We show that the former mismatch affects the
      stability of the zero-lag state but not the dynamics within the synchronization
      manifold, while the latter mismatch does not affect the quality of
      synchronization but alters the dynamics significantly. Our results are extended
      to different unidirectional coupling schemes. This is highly relevant for
      communication schemes utilizing chaotic dynamics. Finally, the influence of
      nonlinear gain saturation on the dynamics and stability of synchronization is
      discussed.

PMID- 21728635
TI  - Defects in spatiotemporal diagrams and their relations to phase coherence and
      lack of observability.
AB  - Spatiotemporal systems are commonly investigated in terms of spatiotemporal
      diagrams and, most often, the analysis is limited to the first instabilities. Due
      to the lack of a Takens-like theorem for spatiotemporal systems, the resulting
      dynamics is almost never interpreted using phase portraits reconstructed from one
      variable locally recorded. This work is an attempt to make an explicit link
      between reconstructed phase portraits and spatiotemporal diagrams. Defects
      distributions are interpreted in terms of a lack of phase coherence. The lack of
      a simple structure--as a torus characterized by a closed curve for Poincare
      section when a quasiperiodic regime is identified--is tentatively interpreted in
      terms of observability. A first link is thus made between the defects
      distribution and the nature of the underlying dynamics.

PMID- 21728636
TI  - Spiral defect drift in the wave fields of multiple excitation patterns.
AB  - Spiral waves in excitable systems decay to drifting defects if forced by high
      frequency wave trains. Using the Barkley model we analyze the drift velocity in
      planar wave trains as a function of wave frequency. Within two antiparallel,
      planar wave trains of equal frequency a defect is pushed into the collision
      region where it stops. Within two circular wave fields, however, it continues its
      drift in a direction perpendicular to the axis connecting the pacemakers.
      Depending on the forcing frequency and the initial position, this motion occurs
      either away from or toward the pacemaker axis. Three circular wave fields can be
      used to position the defect at a unique point close to the center of the
      pacemaker triangle. The results are also observed in experiments with the
      Belousov-Zhabotinsky reaction.

PMID- 21728637
TI  - Exploding dissipative solitons: the analog of the Ruelle-Takens route for
      spatially localized solutions.
AB  - We investigate the route to exploding dissipative solitons in the complex cubic
      quintic Ginzburg-Landau equation, as the bifurcation parameter, the distance from
      linear onset, is increased. We find for a large class of initial conditions the
      sequence: stationary localized solutions, oscillatory localized solutions with
      one frequency, oscillatory localized solutions with two frequencies, and
      exploding localized solutions. The transition between localized solutions with
      one and with two frequencies, respectively, is analyzed in detail. It is found to
      correspond to a forward Hopf bifurcation for these localized solutions as the
      bifurcation parameter is increased. In addition, we make use of power spectra to
      characterize all time-dependent states. On the basis of all information
      available, we conclude that the sequence oscillatory localized solutions with one
      frequency, oscillatory localized solutions with two frequencies, and exploding
      dissipative solitons can be interpreted as the analog of the Ruelle-Takens
      Newhouse route to chaos for spatially localized solutions.

PMID- 21728638
TI  - Stochastic bifurcations in a bistable Duffing-Van der Pol oscillator with colored
      noise.
AB  - This paper aims to investigate Gaussian colored-noise-induced stochastic
      bifurcations and the dynamical influence of correlation time and noise intensity
      in a bistable Duffing-Van der Pol oscillator. By using the stochastic averaging
      method, theoretically, one can obtain the stationary probability density function
      of amplitude for the Duffing-Van der Pol oscillator and can reveal interesting
      dynamics under the influence of Gaussian colored noise. Stochastic bifurcations
      are discussed through a qualitative change of the stationary probability
      distribution, which indicates that system parameters, noise intensity, and noise
      correlation time, respectively, can be treated as bifurcation parameters. They
      also imply that the effects of multiplicative noise are rather different from
      that of additive noise. The results of direct numerical simulation verify the
      effectiveness of the theoretical analysis. Moreover, the largest Lyapunov
      exponent calculations indicate that P and D bifurcations have no direct
      connection.

PMID- 21728639
TI  - Fidelity decay in interacting two-level boson systems: freezing and revivals.
AB  - We study the fidelity decay in the k-body embedded ensembles of random matrices
      for bosons distributed in two single-particle states, considering the reference
      or unperturbed Hamiltonian as the one-body terms and the diagonal part of the k
      body embedded ensemble of random matrices and the perturbation as the residual
      off-diagonal part of the interaction. We calculate the ensemble-averaged fidelity
      with respect to an initial random state within linear response theory to second
      order on the perturbation strength and demonstrate that it displays the freeze of
      the fidelity. During the freeze, the average fidelity exhibits periodic revivals
      at integer values of the Heisenberg time t(H). By selecting specific k-body terms
      of the residual interaction, we find that the periodicity of the revivals during
      the freeze of fidelity is an integer fraction of t(H), thus relating the period
      of the revivals with the range of the interaction k of the perturbing terms.
      Numerical calculations confirm the analytical results.

PMID- 21728640
TI  - Fractal scattering in a radiation field.
AB  - We examine the transfer matrix and the stepping times for chaotic scattering of
      the excess electron in the chlorine ion Cl(-) from the chlorine atom. We use this
      information to determine the fraction of incident trajectories that are reflected
      and transmitted for those electrons caught in the tendrils of the chaotic
      scattering process.

PMID- 21728641
TI  - Separation of deformable particles in deterministic lateral displacement devices.
AB  - Using numerical simulations, we study the separation of deformable bodies, such
      as capsules, vesicles, and cells, in deterministic lateral displacement devices,
      also known as bump arrays. These arrays comprise regular rows of obstacles such
      as micropillars whose arrangements are shifted between adjacent rows by a fixed
      amount. We show that, in addition to the zigzag and laterally displaced
      trajectories that have been observed experimentally, there exists a third type of
      trajectory which we call dispersive, characterized by seemingly random bumpings
      off the micropillars. These dispersive trajectories are observed only for large
      and rigid particles whose diameters are approximately more than half the gap size
      between micropillars and whose stiffness exceeds approximately 500 MPa. We then
      map out the regions in phase space, spanned by the row shift, row separation,
      particle diameter, and particle deformability, in which the different types of
      trajectories are expected. We also show that, in this phase space, it is possible
      to transition from zigzag to dispersive trajectories, bypassing lateral
      displacement. Experimentally, this is undesirable because it limits the ability
      of the device to sort particles according to size. Finally, we discuss how our
      numerical simulations may be of use in device prototyping and optimization.

PMID- 21728642
TI  - Simulation of an ac electro-osmotic pump with step microelectrodes.
AB  - Pumps with step microelectrodes subjected to an ac voltage are known to have
      faster pumping rates than those with planar asymmetric microelectrodes. The
      driving force for pumping in these systems is ac electro-osmosis. This paper aims
      to understand the flow behaviors of pumps with step microelectrodes by using a
      realistic model applicable to high external voltages. This model takes the steric
      effect due to the finite sizes of ions into account and copes with the
      exponential sensitivity of the counterion concentration to voltage. The effects
      on the pumping flow rate of varying the pump parameters were investigated. The
      geometrical parameters were optimized, and the effects of varying the ac
      frequency and amplitude were examined. The electrical potential of the fluid and
      the electrical charge at the electrode surface were solved simultaneously, and
      the Stokes equation was used to describe the fluid flow.

PMID- 21728643
TI  - Elastic vibrations of a fiber due to impact of an aerosol particle and their
      influence on the efficiency of fibrous filters.
AB  - The excitation of sound vibrations of a cylindrical fine fiber due to the impact
      of a spherical aerosol particle is investigated. The equations describing the
      dynamics of impact are derived for an arbitrary shooting parameter. The
      coefficient of restitution is calculated, and its analytical approximation is
      obtained. It is shown, for the case of long fibers, that the coefficient of
      restitution depends upon a single parameter lambda(c). The parameter lambda(c)
      depends on the particle radial velocity component near the fiber surface, the
      mass of the particle, the density of the fiber, the modulus of elasticity, and
      the geometric parameters of the fiber and the particle. The inertial deposition
      of submicron aerosol particles on fine fibers in a filter is considered. The
      efficiency of filtration is studied as a function of the gas flow velocity. The
      existence of a critical flow velocity U(*), below which the losses of particle
      energy during collision have no effect on the efficiency, is demonstrated. For
      velocities higher than the critical velocity, the filtration efficiency is
      dependent on the mechanisms of nonelastic losses of the particle's energy. Its
      value can be significantly lower than that estimated when particle rebound
      effects are neglected. After they have rebounded, some particles are not able to
      attain the initial high velocities in the stream, thus depositing on neighboring
      fibers. The dynamics of these particles is investigated. For this case, it is
      shown that the filtration efficiency is dependent on the velocity distribution of
      the rebounded particles and that it increases with the packing density of fibers.
      A qualitative difference between the asymptotic behavior of a fiber and that of a
      flat plate is found long after the initial impulse.

PMID- 21728644
TI  - 100-Watt sonoluminescence generated by 2.5-atmosphere-pressure pulses.
AB  - A Xenon gas bubble introduced into a vertically suspended steel cylinder is
      driven to sonoluminescence by impacting the apparatus against a solid steel base.
      This produces a 150-ns flash of broadband light that exceeds 100-W peak intensity
      and has a spectral temperature of 10,200 K. This bubble system, which yields
      light with a single shot, emits very powerful sonoluminescence. A jet is visible
      following bubble collapse, which demonstrates that spherical symmetry is not
      necessary to produce sonoluminescence.

PMID- 21728645
TI  - Unexpected water flow through Nafion-tube punctures.
AB  - When a Nafion tube is immersed in water and a small hole is punched in the tube's
      wall, an unexpected phenomenon occurs: Water flows continuously into the tube
      through the hole. The phenomenon has proved repeatable, and dynamic aspects were
      therefore explored, including the effects of altered pH and introduction of a
      second hole. It appears that the flow is closely tied to the recently discovered
      "exclusion zone" that forms as an annulus inside the Nafion tube. These zones
      generate protons in the core of the tube, which exert pressure on the menisci;
      once a hole is punched, the pressure is relieved by sucking water through the
      hole. This hypothesis is consistent with the observed experimental evidence and
      may be relevant to the mechanism of water transport in trees.

PMID- 21728646
TI  - Scalar decay in a three-dimensional chaotic flow.
AB  - The decay of a passive scalar in a three-dimensional chaotic flow is studied
      using high-resolution numerical simulations. The (volume-preserving) flow
      considered is a three-dimensional extension of the randomized alternating sine
      flow employed extensively in studies of mixing in two dimensions. It is used to
      show that theoretical predictions for two-dimensional flows with small
      diffusivity carry over to three dimensions even though the stretching properties
      differ significantly. The variance decay rate, scalar field structure, and time
      evolution of statistical moments confirm that there are two distinct regimes of
      scalar decay: a locally controlled regime, which applies when the domain size is
      comparable to the characteristic length scale of the velocity field, and a
      globally controlled regime, which applies when the domain is larger. Asymptotic
      predictions for the variance decay rate in both regimes show excellent agreement
      with the numerical results. Consideration of both the forward flow and its time
      reverse makes it possible to compare the scalar evolution in flows with one or
      two expanding directions; simulations confirm the theoretical prediction that the
      decay rate of the scalar is the same in both flows, despite the very different
      scalar field structures.

PMID- 21728647
TI  - Hydronium-dominated ion transport in carbon-dioxide-saturated electrolytes at low
      salt concentrations in nanochannels.
AB  - Nanochannel ion transport is known to be governed by surface charge at low ionic
      concentrations. In this paper, we show that this surface charge is typically
      dominated by hydronium ions arising from dissolution of ambient atmospheric
      carbon dioxide. Taking the hydronium ions into account, we model the nanochannel
      conductance at low salt concentrations and identify a conductance minimum before
      saturation at a value independent of salt concentration in the dilute limit. Via
      the Poisson-Boltzmann equation, our model self-consistently couples chemical
      equilibrium dissociation models of the silica wall and of the electrolyte bulk,
      parametrized by the dissociation reaction constants. Experimental data with
      aqueous KCl solutions in 165-nm-high silica nanochannels are described well by
      our model, both with and without extra hydronium from added HCl.

PMID- 21728648
TI  - Meniscus of a ferrofluid around a vertical cylindrical wire carrying electric
      current.
AB  - We study the meniscus profiles of ferrofluids in the magnetic field of a vertical
      current-carrying wire. Measurements of the free ferrofluid surface profile are
      quantitatively compared with numerical calculations. The theoretical model leads
      to a second-order ordinary differential equation. All material parameters are
      determined in independent experiments, therefore no fitting parameters are
      involved in the calculations. The experimental results can be modeled by the
      equilibrium of magnetic, gravitational, and interface tension forces. The
      classical model that neglects interface tension yields significant deviations
      from the experimental profiles in the parameter range studied.

PMID- 21728649
TI  - Transport coefficients for the shear dynamo problem at small Reynolds numbers.
AB  - We build on the formulation developed in S. Sridhar and N. K. Singh [J. Fluid
      Mech. 664, 265 (2010)] and present a theory of the shear dynamo problem for small
      magnetic and fluid Reynolds numbers, but for arbitrary values of the shear
      parameter. Specializing to the case of a mean magnetic field that is slowly
      varying in time, explicit expressions for the transport coefficients alpha(il)
      and eta(il) are derived. We prove that when the velocity field is nonhelical, the
      transport coefficient alpha(il) vanishes. We then consider forced, stochastic
      dynamics for the incompressible velocity field at low Reynolds number. An exact,
      explicit solution for the velocity field is derived, and the velocity spectrum
      tensor is calculated in terms of the Galilean-invariant forcing statistics. We
      consider forcing statistics that are nonhelical, isotropic, and delta correlated
      in time, and specialize to the case when the mean field is a function only of the
      spatial coordinate X(3) and time tau; this reduction is necessary for comparison
      with the numerical experiments of A. Brandenburg, K. H. Radler, M. Rheinhardt,
      and P. J. Kapyla [Astrophys. J. 676, 740 (2008)]. Explicit expressions are
      derived for all four components of the magnetic diffusivity tensor eta(il)(tau).
      These are used to prove that the shear-current effect cannot be responsible for
      dynamo action at small Re and Rm, but for all values of the shear parameter.

PMID- 21728650
TI  - Capillary climb dynamics in the limits of prevailing capillary and gravity force.
AB  - The dynamics of capillary climb of a wetting liquid into a porous medium that is
      opposed by gravity force is studied numerically. We use the capillary network
      model, in which an actual porous medium is represented as a network of pores and
      throats, each following a predefined size distribution function. The liquid
      potential in the pores along the liquid interface within the network is
      calculated as a result of capillary and gravity forces. The solution is general,
      and accounts for changes in the climbing height and climbing velocity. The
      numerical results for the capillary climb reveal that there are at least two
      distinct flow mechanisms. Initially, the flow is characterized by high climbing
      velocity, in which the capillary force is higher than the gravity force, and the
      flow is the viscous force dominated. For this single-phase flow, the Washburn
      equation can be used to predict the changes of climbing height over time. Later,
      for longer times and larger climbing height, the capillary and gravity forces
      become comparable, and one observes a slower increase in the climbing height as a
      function of time. Due to the two forces being comparable, the gas-liquid sharp
      interface transforms into flow front, where the multiphase flow develops. The
      numerical results from this study, expressed as the climbing height as a power
      law function of time, indicate that the two powers, which correspond to the two
      distinct mechanisms, differ significantly. The comparison of the powers with
      experimental data indicates good agreement. Furthermore, the power value from the
      Washburn solution is also analyzed, where it should be equal to 1/2 for purely
      viscous force driven flow. This is in contrast to the power value of ~0.43 that
      is found experimentally. We show from the numerical solution that this
      discrepancy is due to the momentum dissipation on the liquid interface.

PMID- 21728651
TI  - Evolution of the initial hole in vertically vibrated shear thickening fluids.
AB  - The apparent viscosity of shear thickening fluid (STF) changes dramatically with
      the applied shear rate, which is a typical rheological property of STF. Such a
      rheological property affects the vertically vibrated dynamic property of STF. In
      order to get a better understanding of the vertically vibrated dynamic properties
      of STF, the surface instabilities in vertically vibrated STF, which was prepared
      by suspending polymethylmethacrylate particles in ethylene glycol, are
      investigated. Above a critical driving acceleration, the surface instability
      transforms from the disappearance to the fission of the initial hole, which is
      produced by applying a finite perturbation to the surface. The time required for
      the initial hole to disappear can be affected by the driving acceleration,
      vibration frequency, volume fraction, thickness, and shape and size of the
      perturbation. A possible model is proposed, and the expressions of hydrostatic
      force and viscous dissipative force are employed to clarify the relationship
      between disappearance of the hole and shear thickening effect. The fission and
      spreading follow a hexagonal arrangement. At a higher acceleration, the holes
      cover the entire surface in a state of disorder. The mechanism for the initial
      hole's evolution in vertically vibrated shear thickening fluids is discussed.

PMID- 21728652
TI  - Experimental demonstration of the supersonic-subsonic bifurcation in the circular
      jump: a hydrodynamic white hole.
AB  - We provide an experimental demonstration that the circular hydraulic jump
      represents a hydrodynamic white hole or gravitational fountain (the time reverse
      of a black hole) by measuring the angle of the Mach cone created by an object in
      the "supersonic" inner flow region. We emphasize the general character of this
      gravitational analogy by showing theoretically that the white hole horizon
      constitutes a stationary and spatial saddle-node bifurcation within dynamical
      systems theory. We also demonstrate that the inner region has a "superluminal"
      dispersion relation, that is, that the group velocity of the surface waves
      increases with frequency, and discuss some possible consequences with respect to
      the robustness of Hawking radiation. Finally, we point out that our experiment
      shows a concrete example of a possible "trans-Planckian distortion" of black or
      white holes.

PMID- 21728653
TI  - Hydrogen-oxygen flame acceleration and transition to detonation in channels with
      no-slip walls for a detailed chemical reaction model.
AB  - The features of flame acceleration in channels with wall friction and the
      deflagration to detonation transition (DDT) are investigated theoretically and
      using high resolution numerical simulations of two-dimensional reactive Navier
      Stokes equations, including the effects of viscosity, thermal conduction,
      molecular diffusion, and a detailed chemical reaction mechanism for hydrogen
      oxygen gaseous mixture. It is shown that in a wide channel, from the beginning,
      the flame velocity increases exponentially for a short time and then flame
      acceleration decreases, ending up with the abrupt increase of the combustion wave
      velocity and the actual transition to detonation. In a thin channel with a width
      smaller than the critical value, the exponential increase of the flame velocity
      is not bounded and ends up with the transition to detonation. The transition to
      detonation occurs due to the pressure pulse, which is formed at the tip of the
      accelerating flame. The amplitude of the pressure pulse grows exponentially due
      to a positive feedback coupling between the pressure pulse and the heat released
      in the reaction. Finally, large amplitude pressure pulse steepens into a strong
      shock coupled with the reaction zone forming the overdriven detonation. The
      evolution from a temperature gradient to a detonation via the Zeldovich gradient
      mechanism and its applicability to the deflagration-to-detonation transition is
      investigated for combustible materials whose chemistry is governed by chain
      branching kinetics. The results of the high resolution simulations are fully
      consistent with experimental observations of the flame acceleration and DDT.

PMID- 21728654
TI  - Anomalous scaling and solitary waves in systems with nonlinear diffusion.
AB  - We study a nonlinear convective-diffusive equation, local in space and time,
      which has its background in the dynamics of the thickness of a wetting film. The
      presence of a nonlinear diffusion predicts the existence of fronts as well as
      shock fronts. Despite the absence of memory effects, solutions in the case of
      pure nonlinear diffusion exhibit an anomalous subdiffusive scaling. Due to a
      balance between nonlinear diffusion and convection we, in particular, show that
      solitary waves appear. For large times they merge into a single solitary wave
      exhibiting a topological stability. Even though our results concern a specific
      equation, numerical simulations support the view that anomalous diffusion and the
      solitary waves disclosed will be general features in such nonlinear convective
      diffusive dynamics.

PMID- 21728655
TI  - Self-propulsion of a planar electric or magnetic microbot immersed in a polar
      viscous fluid.
AB  - A planar sheet immersed in an electrically polar liquid like water can propel
      itself by means of a plane wave charge density propagating in the sheet. The
      corresponding running electric wave polarizes the fluid and causes an electrical
      torque density to act on the fluid. The sheet is convected by the fluid motion
      resulting from the conversion of rotational particle motion, generated by the
      torque density, into translational fluid motion by the mechanism of friction and
      spin diffusion. Similarly, a planar sheet immersed in a magnetic ferrofluid can
      propel itself by means of a plane wave current density in the sheet and the
      torque density acting on the fluid corresponding to the running wave magnetic
      field and magnetization. The effect is studied on the basis of the micropolar
      fluid equations of motion and Maxwell's equations of electrostatics or
      magnetostatics, respectively. An analytic expression is derived for the velocity
      of the sheet by perturbation theory to second order in powers of the amplitude of
      the driving charge or current density. Under the assumption that the equilibrium
      magnetic equation of state may be used in linearized form and that higher
      harmonics than the first may be neglected, a set of self-consistent integral
      equations is derived which can be solved numerically by iteration. In typical
      situations the second-order perturbation theory turns out to be quite accurate.

PMID- 21728656
TI  - Lagrangian velocity autocorrelations in statistically steady rotating turbulence.
AB  - Lagrangian statistics of passive tracers in rotating turbulence is investigated
      by particle tracking velocimetry. A confined and steadily forced turbulent flow
      is subjected to five different rotation rates. The PDFs of the velocity
      components clearly reveal the anisotropy induced by background rotation. Although
      the statistical properties of the horizontal turbulent flow field are
      approximately isotropic, in agreement with previously reported results by van
      Bokhoven and coworkers [Phys. Fluids 21, 096601 (2009)], the velocity component
      parallel to the (vertical) rotation axis gets strongly reduced (compared to the
      horizontal ones) while the rotation is increased. The auto-correlation
      coefficients of all three components are progressively enhanced for increasing
      rotation rates, although the vertical one shows a tendency to decrease for slow
      rotation rates. The decorrelation is approximately exponential. Lagrangian data
      compare favorably with previously reported Eulerian data for horizontal velocity
      components but show a different behavior for the vertical velocity components at
      higher rotation rates.

PMID- 21728657
TI  - Presence of a Richardson's regime in kinematic simulations.
AB  - In this paper we investigate kinematic simulation (KS) consistency with the
      theory of Richardson [Proc. Roy. Soc. A 110, 24 (1926)] for two-particle
      diffusivity. In particular we revisit the sweeping problem. It has been argued by
      Thomson and Devenish [J. Fluid Mech. 526, 277 (2005).] that due to the lack of
      sweeping of small scales by large scales in kinematic simulation, the validity of
      Richardson's power law might be affected. Here, we argue that the discrepancies
      between authors on the ability of kinematic simulation to predict Richardson
      power law may be linked to the inertial subrange they have used. For small
      inertial subranges, KS is efficient and the significance of the sweeping can be
      ignored, as a result we limit the KS agreement with the Richardson scaling law
      t(3) for inertial subranges k(N0/k(1)<=10000. For larger inertial range KS does
      not fully follow the t(3) law. Unfortunately, there is no experimental data to
      compare KS with and draw conclusions for such large inertial subranges. It cannot
      be concluded either that the discrepancy between KS and Richardson's theory for
      larger inertial subranges is exactly taken into account by the theory developed
      in Thomson and Devenish [J. Fluid Mech. 526, 277 (2005).].

PMID- 21728658
TI  - Effects of polymer additives on Rayleigh-Taylor turbulence.
AB  - The role of polymer additives on the turbulent convective flow of a Rayleigh
      Taylor system is investigated by means of direct numerical simulations of Oldroyd
      B viscoelastic model. The dynamics of polymer elongations follows adiabatically
      the self-similar evolution of the turbulent mixing layer and shows the appearance
      of a strong feedback on the flow which originates a cutoff for polymer
      elongations. The viscoelastic effects on the mixing properties of the flow are
      twofold. Mixing is appreciably enhanced at large scales (the mixing layer growth
      rate is larger than that of the purely Newtonian case) and depleted at small
      scales (thermal plumes are more coherent with respect to the Newtonian case). The
      observed speed up of the thermal plumes, together with an increase of the
      correlations between temperature field and vertical velocity, contributes to a
      significant enhancement of heat transport. Our findings are consistent with a
      scenario of drag reduction induced by polymers. A weakly nonlinear model proposed
      by Fermi for the growth of the mixing layer is reported in the Appendix.

PMID- 21728659
TI  - Symmetrization of a polygonal hollow-core vortex through beat-wave resonance.
AB  - We report on the symmetrization phenomenon of a hollow-core vortex in shallow
      liquid conditions. This phenomenon accompanies the transition of m wave into
      (m+1) wave and involves a beat-wave resonance that mediates energy transfer
      between the background flow and the vortex core. It is shown that this beat wave
      has a frequency m/(m-1)times the frequency of the parent m wave.

PMID- 21728660
TI  - Analytical linear theory for the interaction of a planar shock wave with a two-
      or three-dimensional random isotropic density field.
AB  - We present an analytical linear model describing the interaction of a planar
      shock wave with an isotropic random pattern of density nonuniformities. This kind
      of interaction is important in inertial confinement fusion where shocks travel
      into weakly inhomogeneous cryogenic deuterium-wicked foams, and also in
      astrophysics, where shocks interact with interstellar density clumps. The model
      presented here is based on the exact theory of space and time evolution of the
      perturbed quantities generated by a corrugated shock wave traveling into a small
      amplitude single-mode density field. Corresponding averages in both two and three
      dimensions are obtained as closed analytical expressions for the turbulent
      kinetic energy, acoustic energy flux, density amplification, and vorticity
      generation downstream. They are given as explicit functions of the two parameters
      (adiabatic exponent gamma and shock strength M(1)) that govern the dynamics of
      the problem. In addition, these explicit formulas are simplified in the important
      asymptotic limits of weak and strong shocks and highly compressible fluids.

PMID- 21728661
TI  - Asymmetrical reverse vortex flow due to induced-charge electro-osmosis around
      carbon stacking structures.
AB  - Broken symmetry of vortices due to induced-charge electro-osmosis (ICEO) around
      stacking structures is important for the generation of a large net flow in a
      microchannel. Following theoretical predictions in our previous study, we herein
      report experimental observations of asymmetrical reverse vortex flows around
      stacking structures of carbon posts with a large height (~110 MUm) in water,
      prepared by the pyrolysis of a photoresist film in a reducing gas. Further, by
      the use of a coupled calculation method that considers boundary effects
      precisely, the experimental results, except for the problem of anomalous flow
      reversal, are successfully explained. That is, unlike previous predictions, the
      precise calculations here show that stacking structures accelerate a reverse flow
      rather than suppressing it for a microfluidic channel because of the deformation
      of electric fields near the stacking portions; these structures can also generate
      a large net flow theoretically in the direction opposite that of a previous
      prediction for a standard vortex flow. Furthermore, by solving the one
      dimensional Poisson-Nernst-Plank (PNP) equations in the presence of ac electric
      fields, we find that the anomalous flow reversal occurs by the phase retardation
      between the induced diffuse charge and the tangential electric field. In
      addition, we successfully explain the nonlinearity of the flow velocity on the
      applied voltage by the PNP analysis. In the future, we expect to improve the
      pumping performance significantly by using stacking structures of conductive
      posts along with a low-cost process.

PMID- 21728662
TI  - Development of a swirling double counterflow.
AB  - This numerical study of an axisymmetric motion of a viscous incompressible fluid
      in an elongated cylindrical container explains how a swirling inflow develops the
      global meridional circulation and two U-shaped throughflows (TFs). For moderate
      values of the Reynolds (Re) number, there is a single U-shaped TF: The fluid
      moves from the peripheral annular inlet near the sidewall to the dead end, turns
      around, goes back near the axis, and leaves the container through the central
      exhaust. As Re increases, vortex breakdown occurs near the dead end. If the
      exhaust orifice is wide, the ambient fluid is sucked into the container near its
      axis, reaches the dead-end vicinity, merges with the U-shaped TF, and goes back
      inside an annular region. Thus, a double counterflow develops, where the fluid
      moves to the dead end near both the sidewall and the axis and goes back in
      between. The physical mechanism of the double counterflow is a swirl decay
      combined with the focused flow convergence near the dead end. This double
      counterflow is beneficial for combustion applications.

PMID- 21728663
TI  - Visual analysis of immiscible displacement processes in porous media under
      ultrasound effect.
AB  - The effect of sonic waves, in particular, ultrasonic radiation, on immiscible
      displacement in porous media and enhanced oil recovery has been of interest for
      more than five decades. Attempts were made to investigate the effect through core
      scale experimental or theoretical models. Visual experiments are useful to
      scrutinize the reason for improved oil recovery under acoustic waves of different
      frequency but are not abundant in literature. In this paper, we report
      observations and analyses as to the effects of ultrasonic energy on immiscible
      displacement and interaction of the fluid matrix visually in porous media through
      two-dimensional (2D) sand pack experiments. 2D glass bead models with different
      wettabilities were saturated with different viscosity oils and water was injected
      into the models. The experiments were conducted with and without ultrasound.
      Dynamic water injection experiments were preferred as they had both viscous and
      capillary forces in effect. The displacement patterns were evaluated both in
      terms of their shape, size, and the interface characteristics quantitatively and
      qualitatively to account for the effects of ultrasonic waves on the displacement
      and the reason for increased oil production under this type of sonic wave. More
      compact clusters were observed when ultrasonic energy was present in water-wet
      systems. In the oil-wet cases, more oil was produced after breakthrough when
      ultrasound was applied and no compact clusters were formed in contrast to the
      water-wet cases.

PMID- 21728664
TI  - Nanoscale spiral flow in a cylindrical channel.
AB  - We study the behavior of pressure-driven flow in a cylindrical nanochannel
      patterned with different wettability using molecular dynamics simulations. We
      consider the flow perpendicular or parallel to the periodic stripes of wetting
      and nonwetting materials. For both geometries, we observe a sharp increase in the
      longitudinal velocity of the flow as wetting stripe width decreases, which is
      clearly distinguishable from the case of shear-driven flow. When the channel wall
      is spirally patterned with distinct wetting stripes, the transverse velocity of
      the flow is generated in the channel and its generation depends strongly on the
      degree of molecular ordering above the wetting stripes, which can be controlled
      by helical angle, wetting stripe width, the relative area of the wetting region,
      and the strength of the fluid-wall interaction.

PMID- 21728665
TI  - Perturbed breakup of gas bubbles in water: memory, gas flow, and coalescence.
AB  - The pinch-off of an air bubble from an underwater nozzle ends in a singularity
      with a remarkable sensitivity to a variety of perturbations. I report on
      experiments that break both the axial (i.e., vertical) and azimuthal symmetry of
      the singularity formation. The density of the inner gas influences the axial
      asymmetry of the neck near pinch-off. For denser gases, flow through the neck
      late in collapse changes the pinch-off dynamics. Gas density is also implicated
      in the formation of satellite bubbles. The azimuthal shape oscillations described
      by Schmidt et al. can be initiated by anisotropic boundary conditions in the
      liquid as well as with an asymmetric nozzle shape. I measure the n=3 oscillatory
      mode and observe the nonlinear, highly three-dimensional outcomes of pinch-off
      with large azimuthal perturbations. These are consistent with prior theory.

PMID- 21728666
TI  - Analysis of traveling-wave electro-osmotic pumping with double-sided electrode
      arrays.
AB  - In this paper, a series of numerical simulations was performed to investigate the
      pumping performance of electro-osmotic micropumps containing electrode arrays
      patterned on the upper and lower sides of a microchannel. The simulations have
      been analyzed with a linear electro-osmotic model based upon the Debye-Huckel
      theory of the double layer. The potential drop across the diffuse layer is
      assumed to be less than 25 mV (k(B)T/e), and there is a linear response between
      the surface charge and the voltage drop across the double layer. The double layer
      is not resolved but is lumped into effective parameters that are imported from
      the Debye-Huckel and Stern layers. We examined the effects of the relative
      positioning of the electrodes in the opposing arrays (i.e., symmetrical or
      staggered), and the phase lag and the angular frequency of the alternating
      current (ac) signals applied to the electrodes within the two arrays. A critical
      height of the microchannel was observed, below which the interactions of the
      applied electrical potentials on the walls became significant. The optimum
      pumping effect was obtained when the electrode arrays were symmetrical to one
      another around the centerline of the channel and were activated by ac potentials
      with a 0 degrees  phase shift. The corresponding angular frequency of the maximum
      pumping velocity for different phase shifts of the applied ac signals was also
      determined. Overall, the simulation results presented in this paper provide a
      useful insight into the optimal design parameters and operating conditions for
      micropumps containing two arrays of microelectrodes on the microchannel walls.

PMID- 21728667
TI  - Coiling of yield stress fluids.
AB  - We present an experimental investigation of the coiling of a filament of a yield
      stress fluid falling on a solid surface. We use two kinds of yield stress fluids,
      shaving foam and hair gel, and show that the coiling of the foam is similar to
      the coiling of an elastic rope. Two regimes of coiling (elastic and
      gravitational) are observed for the foam. Hair gel coiling, on the other hand, is
      more like the coiling of a liquid system; here we observe viscous and
      gravitational regimes. No inertial regime is observed for either system because
      of instabilities occurring at high flow rates or the breakup of the filament from
      large heights.

PMID- 21728668
TI  - Gas flow near a smooth plate.
AB  - We examine gas flow adjacent to a molecularly smooth, solid, muscovite mica. The
      fluctuations in force acting on a glass sphere as a function of proximity to a
      mica plate were measured in air and were used to obtain the damping. The damping
      was interpreted as a lubrication force. The measured damping as a function of
      separation in the slip-flow regime corresponds to a slip length of 480 +/- 70 nm,
      which is equivalent to highly specular gas molecule collisions. A slip-flow model
      fits the data for separations as small as one mean free path.

PMID- 21728669
TI  - Collective excitations of a spherically confined Yukawa plasma.
AB  - The complete spectrum of eigenmodes of a spherically confined Yukawa plasma is
      presented, based on first-principle molecular dynamics simulations. These results
      are compared with a recent fluid theory for the multipole modes of this system
      [H. Kahlert and M. Bonitz, Phys. Rev. E 82, 036407 (2010)] and with the exact N
      particle eigenmodes in the crystalline phase. Simulations confirm the existence
      of high-order modes found in cold fluid theory. We investigate the influence of
      screening, coupling, and friction on the mode spectra in detail. Good agreement
      between theory and simulation is found for weak to moderate screening and low
      order modes. In addition, a number of new modes are observed which are missing in
      the fluid theory. The relations between the breathing mode in the fluid theory,
      simulation, and the crystal eigenmode are investigated in further detail.

PMID- 21728670
TI  - Stability of nonlinear Vlasov-Poisson equilibria through spectral deformation and
      Fourier-Hermite expansion.
AB  - We study the stability of spatially periodic, nonlinear Vlasov-Poisson equilibria
      as an eigenproblem in a Fourier-Hermite basis (in the space and velocity
      variables, respectively) of finite dimension, N. When the advection term in the
      Vlasov equation is dominant, the convergence with N of the eigenvalues is rather
      slow, limiting the applicability of the method. We use the method of spectral
      deformation introduced by Crawford and Hislop [Ann. Phys. (NY) 189, 265 (1989)]
      to selectively damp the continuum of neutral modes associated with the advection
      term, thus accelerating convergence. We validate and benchmark the performance of
      our method by reproducing the kinetic dispersion relation results for linear
      (spatially homogeneous) equilibria. Finally, we study the stability of a periodic
      Bernstein-Greene-Kruskal mode with multiple phase-space vortices, compare our
      results with numerical simulations of the Vlasov-Poisson system, and show that
      the initial unstable equilibrium may evolve to different asymptotic states
      depending on the way it was perturbed.

PMID- 21728671
TI  - Simulation of terahertz generation in corrugated plasma waveguides.
AB  - We simulate the response of a corrugated plasma channel to an ultrashort laser
      pulse in two dimensions with the goal of demonstrating the production of
      terahertz frequency electromagnetic modes. Corrugated channels support
      electromagnetic modes that have a Floquet-type dispersion relation and thus
      consist of a sum of spatial harmonics with subluminal phase velocities. This
      allows the possibility of phase matching between the ponderomotive potential
      associated with the laser pulse and the electromagnetic modes of the channel.
      Since the bandwidth of an ultrashort pulse includes terahertz frequencies,
      significant excitation of terahertz radiation is possible. Here we consider
      realistic density profiles to obtain predictions of the terahertz power output
      and mode structure for a channel with periodic boundary conditions. We then
      estimate pulse depletion effects from our simulation results. The fraction of
      laser energy converted to terahertz is independent of laser pulse energy in the
      linear regime, and we find it to be around 1%. Extrapolating to a pulse energy of
      0.5 J gives a terahertz power output of 6 mJ with a pulse depletion length of
      less than 20 cm.

PMID- 21728672
TI  - Classical relativistic model for spin dependence in a magnetized electron gas.
AB  - The response of a cold electron gas is generalized to include the spin of the
      electron described by the relativistically correct quasiclassical Bargmann-Michel
      Telegdi (BMT) equation. The magnetization of the electron gas is assumed to be
      along the background magnetic field B and the spin-dependent contribution to the
      response tensor is proportional to the magnitude of the magnetization. The
      dispersion equation is shown to be quadratic in the refractive index squared, and
      dispersion curves for the two wave modes are plotted for cases where the magnetic
      field associated with magnetization is comparable with B. Two intrinsically spin
      dependent wave modes are identified: one bounded by two resonances and the other
      by two cutoffs. The counterpart of the z mode can escape without encountering a
      resonance or a cutoff.

PMID- 21728673
TI  - Stochastic flux freezing and magnetic dynamo.
AB  - Magnetic flux conservation in turbulent plasmas at high magnetic Reynolds numbers
      is argued neither to hold in the conventional sense nor to be entirely broken,
      but instead to be valid in a statistical sense associated to the "spontaneous
      stochasticity" of Lagrangian particle trajectories. The latter phenomenon is due
      to the explosive separation of particles undergoing turbulent Richardson
      diffusion, which leads to a breakdown of Laplacian determinism for classical
      dynamics. Empirical evidence is presented for spontaneous stochasticity,
      including numerical results. A Lagrangian path-integral approach is then
      exploited to establish stochastic flux freezing for resistive hydromagnetic
      equations and to argue, based on the properties of Richardson diffusion, that
      flux conservation must remain stochastic at infinite magnetic Reynolds number. An
      important application of these results is the kinematic, fluctuation dynamo in
      nonhelical, incompressible turbulence at magnetic Prandtl number (Pr(m)) equal to
      unity. Numerical results on the Lagrangian dynamo mechanisms by a stochastic
      particle method demonstrate a strong similarity between the Pr(m)=1 and 0
      dynamos. Stochasticity of field-line motion is an essential ingredient of both.
      Finally, some consequences for nonlinear magnetohydrodynamic turbulence, dynamo,
      and reconnection are briefly considered.

PMID- 21728674
TI  - Turbulence and bias-induced flows in simple magnetized toroidal plasmas.
AB  - Turbulence and bias-induced flows in simple magnetized toroidal plasmas are
      explored with global three-dimensional fluid simulations, focusing on the
      parameters of the Helimak experiment. The simulations show that plasma turbulence
      and transport in the regime of interest are dominated by the ideal interchange
      instability. The application of a bias voltage alters the structure of the plasma
      potential, resulting in the equilibrium sheared flows.These bias-induced vertical
      flows located in the gradient region appear to reduce the radial extent of
      turbulent structures,and thereby lower the radial plasma transport on the low
      field side.

PMID- 21728675
TI  - Wave dispersion in a counterstreaming, relativistic thermal, magnetized, electron
      positron plasma.
AB  - The dispersion equation is analyzed for waves in a strongly magnetized, electron
      positron plasma in which counterstreaming electrons and positrons have a
      relativistic thermal distribution in their respective rest frames, for
      propagation parallel to the magnetic field. We derive the response tensor for the
      medium, demonstrate the dispersion curves for different temperatures, and discuss
      the differences from the cold-plasma case. Application to the case of pulsar
      magnetospheres is discussed.

PMID- 21728676
TI  - Solitonic propagation and interaction for a generalized variable-coefficient
      forced Korteweg-de Vries equation in fluids.
AB  - Under investigation is a generalized variable-coefficient forced Korteweg-de
      Vries equation in fluids and other fields. From the bilinear form of such
      equation, the N-soliton solution and a type of analytic solution are constructed
      with symbolic computation. Analytic analysis indicates that: (1) dispersive and
      dissipative coefficients affect the solitonic velocity; (2) external-force term
      affects the solitonic velocity and background; (3) line-damping coefficient and
      some parameters affect the solitonic velocity, background, and amplitude.
      Solitonic propagation and interaction can be regarded as the combination of the
      effects of various variable coefficients. According to a constraint among the
      nonlinear, dispersive, and line-damping coefficients in this paper, the possible
      applications of our results in the real world are also discussed in three
      aspects, i.e., solution with the constraint, solution without the constraint, and
      approximate solution.

PMID- 21728677
TI  - Approach to first-order exact solutions of the Ablowitz-Ladik equation.
AB  - We derive exact solutions of the Ablowitz-Ladik (A-L) equation using a special
      ansatz that linearly relates the real and imaginary parts of the complex
      function. This ansatz allows us to derive a family of first-order solutions of
      the A-L equation with two independent parameters. This novel technique shows that
      every exact solution of the A-L equation has a direct analog among first-order
      solutions of the nonlinear Schrodinger equation (NLSE).

PMID- 21728678
TI  - Approximate action-angle variables for the figure-eight and periodic three-body
      orbits.
AB  - We use the maximally permutation-symmetric set of three-body coordinates that
      consist of the "hyper-radius" R=?[rho(2)+lambda(2)], the "rescaled area of the
      triangle" ?[3]/2R(2) |rho*lambda|), and the (braiding) hyperangle
      Phi=arctan(2rho.lambda/lambda(2)-rho(2)) to analyze the "figure-eight"
      choreographic three-body motion discovered by Moore [Phys. Rev. Lett. 70, 3675
      (1993)] in the Newtonian three-body problem. Here rho,lambda are the two Jacobi
      relative coordinate vectors. We show that the periodicity of this motion is
      closely related to the braiding hyperangle Phi. We construct an approximate
      integral of motion G that together with the hyperangle Phi forms the action-angle
      pair of variables for this problem and show that it is the underlying cause of
      figure-eight motion's stability. We construct figure-eight orbits in two other
      attractive permutation-symmetric three-body potentials. We compare the figure
      eight orbits in these three potentials and discuss their generic features, as
      well as their differences. We apply these variables to two new periodic, but
      nonchoreographic, orbits: One has a continuously rising Phi in time t, just like
      the figure-eight motion, but with a different, more complex, periodicity, whereas
      the other one has an oscillating Phi(t) temporal behavior.

PMID- 21728679
TI  - Frequency dependence of the subharmonic Shapiro steps.
AB  - Frequency dependence of the subharmonic Shapiro steps has been studied in the ac
      driven overdamped Frenkel-Kontorova model with deformable substrate potential. As
      potential gets deformed, in addition to the harmonic steps, subharmonic steps
      appear in the number and size that increase as the frequency of the external
      force increases. It was found that size of both harmonic and subharmonic steps
      strongly depend on the frequency where in the high-amplitude limit oscillatory
      dependence appears. When expressed as a function of period these oscillations of
      the step size with frequency have the same form as the oscillations of the step
      size with amplitude. Deformation of the potential has strong influence on these
      oscillations, and as in the case of amplitude dependence, with the increase of
      deformation, the same three distinctive types of behavior have been classified.

PMID- 21728680
TI  - Asymmetric energy flux in a transmission line based on frequency multiplication.
AB  - We experimentally investigate the energy flux in a nonlinear electrical
      transmission line formed by two segments which are identical in structure but
      have different parameters. By consideration of the driving voltage at a frequency
      within the passband of one segment, the phenomenon of asymmetric energy flux
      caused by linear waves has been observed. The experiment shows that the
      possibility of creation of an asymmetric energy flux mainly depends on the
      nonlinear and lattice effects; namely, the asymmetric energy flux here is carried
      by a linear wave in the passband, instead of by a nonlinear wave out of the band.
      To further understand this phenomenon in the transmission line, we study both
      experimentally and numerically the dependency of the asymmetric energy flux on
      the parameters, and the key factors which affect the efficiency of the asymmetric
      energy flux are obtained.

PMID- 21728681
TI  - Quantized representation of some nonlinear integrable evolution equations on the
      soliton sector.
AB  - The Hirota algorithm for solving several integrable nonlinear evolution equations
      is suggestive of a simple construction of a quantized representation of these
      equations and their soliton solutions over a Fock space of bosons or of fermions.
      The classical nonlinear wave equation becomes a nonlinear equation for an
      operator. The solution of this equation is constructed through an operator analog
      of the Hirota transformation. The classical N-soliton solution is the expectation
      value of the solution operator in an N-particle state in the Fock space. The
      effect of perturbations that modify soliton identity is demonstrated.

PMID- 21728682
TI  - Externally driven transmission and collisions of domain walls in ferromagnetic
      wires.
AB  - Analytical multidomain solutions to the dynamical (Landau-Lifshitz-Gilbert)
      equation of a one-dimensional ferromagnet including an external magnetic field
      and spin-polarized electric current are found using the Hirota bilinearization
      method. A standard approach to solve the Landau-Lifshitz equation (without the
      Gilbert term) is modified in order to treat the dissipative dynamics. I establish
      the relations between the spin interaction parameters (the constants of exchange,
      anisotropy, dissipation, external-field intensity, and electric-current
      intensity) and the domain-wall parameters (width and velocity) and compare them
      to the results of the Walker approximation and micromagnetic simulations. The
      domain-wall motion driven by a longitudinal external field is analyzed with
      especial relevance to the field-induced collision of two domain walls. I
      determine the result of such a collision (which is found to be an elastic one) on
      the domain-wall parameters below and above the Walker breakdown (in weak- and
      strong-field regimes). Single-domain-wall dynamics in the presence of an external
      transverse field is studied with relevance to the challenge of increasing the
      domain-wall velocity below the breakdown.

PMID- 21728683
TI  - Externally driven collisions of domain walls in bistable systems near
      criticality.
AB  - Multidomain solutions to the time-dependent Ginzburg-Landau equation in the
      presence of an external field are analyzed using the Hirota bilinearization
      method. Domain-wall collisions are studied in detail considering different
      regimes of the critical parameter. I show the dynamics of the Ising and Bloch
      domain walls of the Ginzburg-Landau equation in the bistable regime to be similar
      to that of the Landau-Lifshitz domain walls. Domain-wall reflections lead to the
      appearance of bubble and pattern structures. Above the Bloch-Ising transition
      point, spatial structures are determined by the collisions of fronts propagating
      into an unstable state. Mutual annihilation of such fronts is described.

PMID- 21728684
TI  - Time-periodic solitons in a damped-driven nonlinear Schrodinger equation.
AB  - Time-periodic solitons of the parametrically driven damped nonlinear Schrodinger
      equation are obtained as solutions of the boundary-value problem on a two
      dimensional spatiotemporal domain. We follow the transformation of the periodic
      solitons as the strength of the driver is varied. The resulting bifurcation
      diagrams provide a natural explanation for the overall form and details of the
      attractor chart compiled previously via direct numerical simulations. In
      particular, the diagrams confirm the occurrence of the period-doubling transition
      to temporal chaos for small values of dissipation and the absence of such
      transitions for larger dampings. This difference in the soliton's response to the
      increasing driving strength can be traced to the difference in the radiation
      frequencies in the two cases. Finally, we relate the soliton's temporal chaos to
      the homoclinic bifurcation.

PMID- 21728685
TI  - Soliton complexity in the damped-driven nonlinear Schrodinger equation:
      stationary to periodic to quasiperiodic complexes.
AB  - Stationary and oscillatory bound states, or complexes, of the damped-driven
      solitons are numerically path-followed in the parameter space. We compile a chart
      of the two-soliton attractors, complementing the one-soliton attractor chart.

PMID- 21728686
TI  - Localization-delocalization transition and subdiffusion of discrete nonlinear
      Schrodinger equation in three dimensions.
AB  - Localization-delocalization transition in a three-dimensional discrete nonlinear
      Schrodinger equation (DNLSE) with random potential is investigated, and the
      effect of nonlinearity is clarified numerically. By Thouless-number analysis, it
      is shown that the nonlinearity tends to delocalize the stationary states in a
      three-dimensional DNLSE. The spreading of a wave packet in a localized regime is
      also clarified for this system, and the subdiffusive behavior is observed in the
      three-dimensional system when the nonlinearity of the system is sufficiently
      strong. In addition, a one-dimensional DNLSE with random potential having a
      finite correlation length is studied, and it is suggested that the power-law
      exponent of the subdiffusion in DNLSE is not a universal quantity.

PMID- 21728687
TI  - Monte Carlo algorithm for simulating reversible aggregation of multisite
      particles.
AB  - We present an efficient and exact Monte Carlo algorithm to simulate reversible
      aggregation of particles with dedicated binding sites. This method introduces a
      data structure of dynamic bond trees to record clusters and sequences of bond
      formations. The algorithm achieves a constant time cost for processing cluster
      association and a cost between O(logM) and O(M) for processing bond dissociation
      in clusters with M bonds. The algorithm is statistically exact and can reproduce
      results obtained by the standard method. We applied the method to simulate a
      trivalent ligand and a bivalent receptor clustering system and obtained an
      average scaling of O(M(0.45)) for processing bond dissociation in acyclic
      aggregation, compared to a linear scaling with the cluster size in standard
      methods. The algorithm also demands substantially less memory than the
      conventional method.

PMID- 21728688
TI  - Robust numerical method for integration of point-vortex trajectories in two
      dimensions.
AB  - The venerable two-dimensional (2D) point-vortex model plays an important role as
      a simplified version of many disparate physical systems, including superfluids,
      Bose-Einstein condensates, certain plasma configurations, and inviscid
      turbulence. This system is also a veritable mathematical playground, touching
      upon many different disciplines from topology to dynamic systems theory. Point
      vortex dynamics are described by a relatively simple system of nonlinear ordinary
      differential equations which can easily be integrated numerically using an
      appropriate adaptive time stepping method. As the separation between a pair of
      vortices relative to all other intervortex length scales decreases, however, the
      computational time required diverges. Accuracy is usually the most discouraging
      casualty when trying to account for such vortex motion, though the varying energy
      of this ostensibly Hamiltonian system is a potentially more serious problem. We
      solve these problems by a series of coordinate transformations: We first
      transform to action-angle coordinates, which, to lowest order, treat the close
      pair as a single vortex amongst all others with an internal degree of freedom. We
      next, and most importantly, apply Lie transform perturbation theory to remove the
      higher-order correction terms in succession. The overall transformation
      drastically increases the numerical efficiency and ensures that the total energy
      remains constant to high accuracy.

PMID- 21728689
TI  - Plaquette renormalization scheme for tensor network states.
AB  - We present a method for contracting a square-lattice tensor network in two
      dimensions based on auxiliary tensors accomplishing successive truncations
      (renormalization) of eight-index tensors for 2 * 2 plaquettes into four-index
      tensors. Since all approximations are done on the wave function (which also can
      be interpreted in terms of different kinds of tensor networks), the scheme is
      variational, and thus, the tensors can be optimized by minimizing the energy.
      Test results for the quantum phase transition of the transverse-field Ising model
      confirm that even the smallest possible tensors (two values for each tensor index
      at each renormalization level) produce much better results than the simple
      product (mean-field) state.

PMID- 21728690
TI  - Lattice Boltzmann study on Kelvin-Helmholtz instability: roles of velocity and
      density gradients.
AB  - A two-dimensional lattice Boltzmann model with 19 discrete velocities for
      compressible fluids is proposed. The fifth-order weighted essentially
      nonoscillatory (5th-WENO) finite difference scheme is employed to calculate the
      convection term of the lattice Boltzmann equation. The validity of the model is
      verified by comparing simulation results of the Sod shock tube with its
      corresponding analytical solutions [G. A. Sod, J. Comput. Phys. 27, 1 (1978).].
      The velocity and density gradient effects on the Kelvin-Helmholtz instability
      (KHI) are investigated using the proposed model. Sharp density contours are
      obtained in our simulations. It is found that the linear growth rate gamma for
      the KHI decreases by increasing the width of velocity transition layer D(v) but
      increases by increasing the width of density transition layer D(rho). After the
      initial transient period and before the vortex has been well formed, the linear
      growth rates gamma(v) and gamma(rho), vary with D(v) and D(rho) approximately in
      the following way, lngamma(v)=a-bD(v) and
      gamma(rho)=c+elnD(rho)(D(rho)<D(rho)(E)), where a, b, c, and e are fitting
      parameters and D(rho)(E) is the effective interaction width of the density
      transition layer. When D(rho)>D(rho)(E) the linear growth rate gamma(rho) does
      not vary significantly any more. One can use the hybrid effects of velocity and
      density transition layers to stabilize the KHI. Our numerical simulation results
      are in general agreement with the analytical results [L. F. Wang et al., Phys.
      Plasma 17, 042103 (2010)].

PMID- 21728691
TI  - Speeding up simulation of diffusion in zeolites by a parallel synchronous kinetic
      Monte Carlo algorithm.
AB  - Understanding the behaviors of molecules in tight confinement is a challenging
      task. Standard simulation tools like kinetic Monte Carlo have proven to be very
      effective in the study of adsorption and diffusion phenomena in microporous
      materials, but they turn out to be very inefficient when simulation time and
      length scales are extended. In this paper we have explored the possibility of
      application of a discrete version of the synchronous parallel kinetic Monte Carlo
      algorithm introduced by Martinez et al. [J. Comput. Phys. 227, 3804 (2008)] to
      the study of aromatic hydrocarbons diffusion in zeolites. The efficiency of this
      algorithm is investigated as a function of the number of processors and domain
      size. We show that with an accurate choice of domains size it is possible to
      achieve very good efficiencies thus permitting us to effectively extend space and
      time scales of the simulated system.

PMID- 21728692
TI  - Kapitza resistance in the lattice Boltzmann-Peierls-Callaway equation for
      multiphase phonon gases.
AB  - The interface thermal resistance becomes more and more important as device
      miniaturization for better performance renders a large surface-to-volume ratio
      and invariably requires a device design with multiple materials inducing thermal
      interfaces across the material heterogeniety. Toward developing a comprehensive
      computational methodology for thermal transport prediction, incorporating the
      interface effects in a heterogeneous medium, a novel boundary collision rule is
      devised in the lattice Boltzmann computational scheme to realize a thermal
      interface between phonon gases with dissimilar dispersion relations. Consistent
      with the Callaway collision operator for Umklapp process, the interface phonon
      collision process is regarded as a linear relaxation mechanism toward the local
      pseudo-equilibrium phonon distribution, which is uniquely defined by the energy
      conservation principle. The Kapitza length and the interface thermal resistance
      are determined by the relaxation parameter and the local phonon properties. The
      implementation of the proposed mesoscopic boundary collision rule in the lattice
      Boltzmann computational framework provides a methodology of predicting the
      thermal properties of a heterogeneus medium incorporating both normal and Umklapp
      collision processes of phonon.

PMID- 21728693
TI  - Shower approach in the simulation of ion scattering from solids.
AB  - An efficient approach for the simulation of ion scattering from solids is
      proposed. For every encountered atom, we take multiple samples of its thermal
      displacements among those which result in scattering with high probability to
      finally reach the detector. As a result, the detector is illuminated by intensive
      "showers," where each event of detection must be weighted according to the actual
      probability of the atom displacement. The computational cost of such simulation
      is orders of magnitude lower than in the direct approach, and a comprehensive
      analysis of multiple and plural scattering effects becomes possible. We use this
      method for two purposes. First, the accuracy of the approximate approaches,
      developed mainly for ion-beam structural analysis, is verified. Second, the
      possibility to reproduce a wide class of experimental conditions is used to
      analyze some basic features of ion-solid collisions: the role of double violent
      collisions in low-energy ion scattering; the origin of the "surface peak" in
      scattering from amorphous samples; the low-energy tail in the energy spectra of
      scattered medium-energy ions due to plural scattering; and the degradation of
      blocking patterns in two-dimensional angular distributions with increasing depth
      of scattering. As an example of simulation for ions of MeV energies, we verify
      the time reversibility for channeling and blocking of 1-MeV protons in a W
      crystal. The possibilities of analysis that our approach offers may be very
      useful for various applications, in particular, for structural analysis with
      atomic resolution.

PMID- 21728694
TI  - Using normal modes to calculate and optimize thermal conductivity in
      functionalized macromolecules.
AB  - The quest for high thermal conductivity materials has led to nanocomposites
      incorporating macromolecular materials with excellent thermal conductivity, such
      as carbon nanotubes and graphene nanoribbons, in a matrix of poorer thermal
      conductivity. To minimize the interface thermal resistance the stiff,
      incorporated materials can be chemically functionalized with various side chains.
      We report here an efficient theoretical method using normal modes to calculate
      the thermal conductivity of such systems and show how the participation ratio of
      these modes can be used to evaluate different choices for functionalization. We
      use this method to examine how effective different alkane chains improve the heat
      flux through a graphene nanosheet.

PMID- 21728695
TI  - Three-layer dielectric models for generalized Coulomb potential calculation in
      ellipsoidal geometry.
AB  - This paper concerns a basic electrostatic problem: how to calculate generalized
      Coulomb and self-polarization potentials in heterogeneous dielectric media. In
      particular, with simulations of ellipsoidal semiconductor quantum dots and
      elongated biomacromolecules being its target applications, this paper extends the
      so-called three-layer dielectric models for generalized Coulomb and self
      polarization potential calculation from the spherical and the spheroidal
      geometries to the triaxial ellipsoidal geometry. Compared to the simple steplike
      dielectric model, these three-layer dielectric models can overcome the
      mathematical divergence in the self-polarization energy by employing continuous
      radial dielectric functions. More specifically, in this paper, the quasiharmonic
      three-layer dielectric model for the ellipsoidal geometry is discussed, and the
      explicit analytical series solutions of the corresponding electrostatic problem
      are obtained in terms of the ellipsoidal harmonics. Then a robust numerical
      procedure working for general three-layer dielectric models is developed. The key
      component of the numerical method is to subdivide the transition layer of the
      underlying three-layer model into multiple sublayers and then in each one of them
      approximate the select dielectric function of the transition layer by one of the
      quasiharmonic functional form rather than simply by a constant value as one would
      normally do. As a result, the numerical method has no numerical divergence.

PMID- 21728696
TI  - Numerics of the lattice Boltzmann method: effects of collision models on the
      lattice Boltzmann simulations.
AB  - We conduct a comparative study to evaluate several lattice Boltzmann (LB) models
      for solving the near incompressible Navier-Stokes equations, including the
      lattice Boltzmann equation with the multiple-relaxation-time (MRT), the two
      relaxation-time (TRT), the single-relaxation-time (SRT) collision models, and the
      entropic lattice Boltzmann equation (ELBE). The lid-driven square cavity flow in
      two dimensions is used as a benchmark test. Our results demonstrate that the ELBE
      does not improve the numerical stability of the SRT or the lattice Bhatnagar
      Gross-Krook (LBGK) model. Our results also show that the MRT and TRT LB models
      are superior to the ELBE and LBGK models in terms of accuracy, stability, and
      computational efficiency and that the ELBE scheme is the most inferior among the
      LB models tested in this study, thus is unfit for carrying out numerical
      simulations in practice. Our study suggests that, to optimize the accuracy,
      stability, and efficiency in the MRT model, it requires at least three
      independently adjustable relaxation rates: one for the shear viscosity nu (or the
      Reynolds number Re), one for the bulk viscosity zeta, and one to satisfy the
      criterion imposed by the Dirichlet boundary conditions which are realized by the
      bounce-back-type boundary conditions.

PMID- 21728697
TI  - Cooperation in scale-free networks with limited associative capacities.
AB  - In this work we study the effect of limiting the number of interactions (the
      associative capacity) that a node can establish per round of a prisoner's dilemma
      game. We focus on the way this limitation influences the level of cooperation
      sustained by scale-free networks. We show that when the game includes cooperation
      costs, limiting the associative capacity of nodes to a fixed quantity renders in
      some cases larger values of cooperation than in the unrestricted scenario. This
      allows one to define an optimum capacity for which cooperation is maximally
      enhanced. Finally, for the case without cooperation costs, we find that even a
      tight limitation of the associative capacity of nodes yields the same levels of
      cooperation as in the original network.

PMID- 21728698
TI  - Diversity and critical behavior in prisoner's dilemma game.
AB  - The prisoner's dilemma (PD) game is a simple model for understanding cooperative
      patterns in complex systems. Here, we study a PD game problem in scale-free
      networks containing hierarchically organized modules and controllable shortcuts
      connecting separated hubs. We find that cooperator clusters exhibit a percolation
      transition in the parameter space (p,b), where p is the occupation probability of
      shortcuts and b is the temptation payoff in the PD game. The cluster size
      distribution follows a power law at the transition point. Such a critical
      behavior, resulting from the combined effect of stochastic processes in the PD
      game and the heterogeneity of complex network structure, illustrates diversities
      arising in social relationships and in forming cooperator groups in real-world
      systems.

PMID- 21728699
TI  - Synchronization patterns in transient spiral wave dynamics.
AB  - Transient dynamics of spiral waves in a two-dimensional Barkley model is shown to
      be governed by pattern formation processes resulting in regions of synchronized
      activity separated by moving interfaces. During the transient the number of
      internally synchronized regions decreases as synchronization fronts move to the
      boundary of the simulated area. This spatiotemporal transient dynamics in an
      excitable medium is detected and visualized by means of an analysis of the local
      periodicity and by evaluation of prediction errors across the spatial domain.
      During the (long) transient both analyses show patterns that must not be
      misinterpreted as any information about (spatial) structure of the underlying
      (completely homogeneous) system.

PMID- 21728700
TI  - Electromagnetic surface modes in a magnetized quantum electron-hole plasma.
AB  - The propagation of surface electromagnetic waves along a uniform magnetic field
      is studied in a quantum electron-hole semiconductor plasma. A forward propagating
      mode is found by including the effect of quantum tunneling. In the classical
      limit (h->0), one of the low-frequency modes found is similar to an
      experimentally observed one in n-type InSb at room temperature. The surface modes
      are shown to be significantly modified in the case of high-conductivity
      semiconductor plasmas where electrons and holes may be degenerate. The effects of
      the external magnetic field and the quantum tunneling on the surface wave modes
      are discussed.

PMID- 21728701
TI  - Closure schemes in stochastic nonlinear dynamics: a validation case study.
AB  - It is known that randomness in dynamical systems often leads to infinite
      hierarchies of coupled equations for relevant probabilistic quantities. Several
      closure methods for truncation of the hierarchies have been proposed in the
      literature. In the present paper the performance of closure schemes for moment
      hierarchies is compared by using the well-known nonlinear equation of overdamped
      oscillator with additive Gaussian white noise. In the case of bistable dynamics
      it is shown that the closure schemes can give incorrect results despite of their
      good convergence properties. To overcome this deficiency new closure procedures
      are proposed. They are based on using the Hermite polynomials and their
      generalization.

PMID- 21728702
TI  - Perinatal death and neurological damage as a sequential chain of poor outcome.
AB  - OBJECTIVE: We investigated the risk factors of perinatal death and neurological
      damage. METHODS: Perinatal death and neurological damage were retrospectively
      investigated using a population-based study of 108 024 deliveries from 1998 to
      2007. Main factors studied were asphyxia, growth restriction and preterm delivery
      < 34 weeks of gestation, since these three factors were most often associated
      with poor prognosis. The impact of each factor was identified by multiple
      regression analyses. RESULTS: There were 459 perinatal deaths (4.3/1000) and 220
      neurological damages (2.0/1000). Preterm delivery accounted for 50% of perinatal
      deaths and neurological damage, whereas it constituted 2.6% of total births.
      Multiple regression analyses showed that prematurity < 34 weeks (10-fold),
      asphyxia (10-fold) and growth restriction (2-fold) were independent and
      significant risk factors associated with poor outcomes, and that the magnitude
      was similar throughout the three consecutive critical events of fetal death,
      neonatal death and neurological damage. CONCLUSIONS: Prematurity < 34 weeks,
      asphyxia and growth restriction are independent and persistent risk factors from
      perinatal death to neurological damage.

PMID- 21728704
TI  - The abject self: self-states of relentless despair.
AB  - Early childhood deprivation, attachment chaos, repeated medical traumata, and
      abuse set up neural networks of dread, shame, worthlessness, and hopelessness:
      the phenomenology of abject experience that resides in implicit memory. Abject
      interactions with others condense yearning and despair into complex enactments of
      abject suffering. Working in abject subgroups dilutes the intensity of abject
      material as ownership of toxic affects is broadened. Affective engagement and a
      relational perspective facilitate the management and transformation of self
      abjection into more optimal relatedness in combined group and individual
      treatment.

PMID- 21728705
TI  - Practice-based evidence: patients who did not respond to group analysis.
AB  - Evidence-based psychotherapy is typically based on treatment outcome for the
      "average" patient in aggregate designs; reports on individual non-responders are
      rarely published. In this observational study, we explored factors that might
      have contributed to non-response in long-term dynamic group psychotherapy. Eight
      patients (14%) who did not change were compared with 48 treatment responders on
      clinical variables, and their case stories were retrospectively scrutinized for
      explanatory factors. The non-responders had less initial distress, stayed for
      shorter durations in therapy, and were more dissatisfied with their group and
      therapists. Based on detailed case stories, attempts are made to tease out
      idiographic hypotheses why each patient did not change during group analysis.

PMID- 21728706
TI  - Coming to our senses: the application of somatic psychology to group
      psychotherapy.
AB  - Somatic psychology, the interplay of the body, the mind, the emotions, and the
      social context, significantly contributes to the theory and practice of group
      therapy. The processing of sensory experiences in the here-and-now of the therapy
      group helps group members to develop self-awareness, the ability to understand
      their relationships with others, and the capacity for empathy. When group members
      know what they experience, they can understand how others feel and resonate
      emotionally with those feelings. Neurobiology, sensory processing, and attachment
      theories help us to understand how the sense of self develops somatically.
      Principles of somatic therapies are applied to group therapy practice in working
      with attachment disorders, transference impasse, and trauma. The importance and
      implications of the group therapist's embodied attunement are explored.

PMID- 21728707
TI  - Ladies in waiting: a group intervention for families coping with deployed
      soldiers.
AB  - It is widely recognized that military service during wartime can take a toll on a
      soldier's psychological health. Recent work has revealed effects on the families
      left behind as well, as reflected, for example, in an increase in child abuse and
      neglect in these families. My interest in studying the transgenerational
      transmission of trauma led me to offer the National Guard a pro bono group
      therapy for women whose husbands had been deployed overseas. A slightly
      unorthodox approach paved the way not only to group treatment but, ultimately,
      individual treatment for these women and their children. My hope is that this
      work can serve as a model for other therapists who share my interest in treating
      the intergenerational transmission of trauma by implementing group and mother
      child psychotherapy.

PMID- 21728708
TI  - Cognitive behavioral group treatment for Chinese people with depressive symptoms
      in Hong Kong: participants' perspectives.
AB  - This study documents the experiences of 20 Chinese people in Hong Kong who
      participated in group cognitive behavioral therapy (CBT). They were asked to
      comment on the aspects of the group content and process that they found to be
      useful or not useful in dealing with their depressive moods. In general, they
      reported that the groups helped them gain awareness of their thought and
      behavioral patterns and learn new cognitive and behavioral strategies. Certain
      aspects of the group process, however, such as the outpouring of negative
      emotions, were considered by the participants to be counterproductive to their
      learning and practice of CBT.

PMID- 21728709
TI  - Editor's note.

PMID- 21728710
TI  - Group therapy with patients suffering from medical illnesses.

PMID- 21728717
TI  - Pulmonary complications in survivors of childhood hematological malignancies:
      single-center experience.
AB  - Children treated for cancer face the risk of complications later in life,
      including pulmonary dysfunction. The objective of this study was to evaluate
      frequency and severity of pulmonary complications in survivors of childhood
      leukemia and lymphoma treated with chemotherapy alone or combined with
      radiotherapy. Seventy cancer survivors of hematological malignancies were
      evaluated for pulmonary complications through history taking, chest examination,
      high-resolution computed tomography (HRCT) chest, and pulmonary function testing
      (PFTs). Although most survivors were not clinically compromised, the spectrum of
      impaired PFTs included obstructive pattern (14.3%), restrictive pattern (5.7%),
      and mixed pattern (20%). Significant pulmonary dysfunction was seen in children
      older than 10 years of age (P = .003), and in patients treated with combined
      chemotherapy and radiotherapy (72.7%) compared with those treated with
      chemotherapy alone (25%) (P = .001). Cumulative dose of bleomycin was
      significantly associated with abnormal PFTs (P = .04). Multivariate analysis
      revealed methotrexate therapy as significant predictor of abnormal PFTs (P =
      .002). Male patients who received combined therapy showed higher frequency of
      restrictive, obstructive lung disease, abnormal respiratory reactance, and
      peripheral airway disease (P = .007, P = .04, P = .002, P = .003, P = .05,
      respectively). Those with abnormal CT findings (n = 14) had lower forced vital
      capacity (FVC%), forced expiratory volume in 1 second (FEV(1)%), and peak
      expiratory flow (PEF%) when compared to cases with normal CT (P = .001, P <
      0.001, P = .001, respectively). Subclinical pulmonary function abnormalities are
      found in survivors of childhood hematological malignancies previously treated and
      off therapy. Pulmonary dysfunction is more evident with combined chemotherapy and
      radiotherapy, bleomycin, and methotrexate are the most incriminated
      chemotherapeutic agents, and males are at higher risk than females; therefore a
      specific and extended follow-up is warranted.

PMID- 21728718
TI  - Gene expression of TRK neurotrophin receptors in advanced neuroblastomas in
      Singapore--a pilot study.
AB  - The clinical hallmark of neuroblastoma is heterogeneity. Biologically, ploidy and
      N-Myc amplification are currently the only 2 features used to define risk group
      and to determine therapy. Tyrosine kinase neurotrophin receptors (Trks, including
      TrkA, TrkB, and TrkC) are important in the clinical and biological behavior of
      neuroblastomas. The authors aim to study Trks gene expression in their local
      population of advanced neuroblastoma patients. Multiplex reverse transcriptase
      polymerase chain reaction (RT-PCR) assay on the expression of TrkA, TrkB, TrkB
      truncated, and TrkC was performed on a total of 19 advanced neuroblastoma
      archival tumors, diagnosed in KK Women's and Children's Hospital between 2003 and
      2007. Of the 19 tumors investigated, Trks expression was present in 14 (73.6%)
      cases. Of these cases, 8 (42.1%), 10 (52.6%), 7 (36.8%), and 6 (31.6%) expressed
      TrkA, TrkB, TrkB-truncated, and TrkC receptor mRNAs, respectively. Subsequently,
      the authors compared Trks expression with N-Myc amplification status of the 19
      patients. N-Myc was amplified in 5 (26.3%) of the cases. Within the non-N-Myc
      amplified group, Trks expression was present in 9 (64%) of the 14 cases. The
      significant expression of Trk isoforms among advanced neuroblastoma cases as
      evident from this study support their role as possible risk assessment tools
      alongside N-Myc amplification status.

PMID- 21728719
TI  - A leukemia/lymphoma with lymphoblastic morphology and l3 morphologic relapse.

PMID- 21728720
TI  - Complications of beta-thalassemia intermedia in Iran during 1996-2010 (single
      center study).
AB  - Patients with thalassemia intermedia (TI) experience many complications, of which
      the incidence varies greatly among cases. Considering the high prevalence of
      thalassemia in Iran, the study was carried out to determine the frequency of TI
      complications in Iranian patients and to find possible risk factors for each of
      them. Using the sampling method of "census," the authors included 153 patients
      who were seen in their tertiary hematology clinic with the diagnosis of TI during
      1996-2010; an analytical cross-sectional study was performed and the data was
      analyzed by SPSS software using univariate and regression analyses. Mean age of
      the patients at the time of the study was 17.4 years and 36.5% were receiving
      transfusions (regularly or occasionally). Mean hemoglobin was 9.2 g/dL and mean
      serum ferritin was 858 ng/mL. Splenectomy was performed in 46.9% and it was
      correlated with age and the age at diagnosis in regression analysis.
      Cholelithiasis was found in 25.5% and was correlated with age and history of
      splenectomy. Pulmonary hypertension, detected in 23.5%, was correlated with
      thrombocytosis and mitral valve regurgitation in univariate analysis. Endocrine
      disease (hypogonadism, hypothyroidism, and adrenal insufficiency) was detected in
      8% of the patients. In univariate analysis, endocrine disease was correlated with
      age of the patients. Regarding bone density of the spine, 53% of cases had
      osteoporosis. Thrombocytosis was present in 42% of patients and was correlated
      with their age. Since the severity of thalassemia intermedia vary greatly among
      patients, a careful evaluation of clinical, laboratory, and genetic aspects is
      necessary to differentiate TI in a patient at presentation. Moreover, TI patients
      should be carefully followed up for early detection and management of newly
      developed complications. The authors also suggest confirmatory controlled studies
      with larger sample sizes to assist in developing guidelines for surveillance and
      treatment of TI.

PMID- 21728721
TI  - Diagnostic yield of upper gastrointestinal endoscopy in the evaluation of iron
      deficiency anemia in older children and adolescents.
AB  - Iron deficiency anemia (IDA) is frequent in childhood. Inadequate nutrition and
      gastrointestinal malabsorption are the frequent causes of IDA in children. But
      reduced iron absorption and insidious blood loss from the gastrointestinal tract
      has been identified as the most frequent causes of IDA in older children and
      adolescents. Therefore the authors evaluated the frequency and etiologies of the
      upper gastrointestinal system pathologies causing IDA in older pediatric
      population. Patients with known hematological or chronic diseases, heavy
      menstrual flow, and obvious blood loss were excluded from the study. Forty-four
      children between the ages of 9.5 and 17.5 years and diagnosed with IDA were
      enrolled. They underwent upper gastrointestinal endoscopy and biopsy from
      esophagus, stomach, and duodenum. Mean age and hemoglobin (Hb) levels of study
      group (32 boys, and 12 girls) were 14.6 +/- 2.0 years and 7.9 +/- 1.8 g/dL,
      respectively. Only 1 patient had a positive serology testing with anti-tissue
      transglutaminase and small bowel biopsy correlating with celiac disease.
      Endoscopy revealed abnormal findings in 25 (56.8%) patients (21 endoscopic antral
      gastritis, 2 active duodenal ulcers, and 2 duodenal polyps). Helicobacter pylori
      (HP) infection was identified by using antral histopathological evaluation in 19
      of 44 children (43.2%). In 2 of duodenal samples, one patient had celiac disease,
      and the other one was diagnosed as giardiasis. In conclusion, there are different
      etiologies resulting in IDA in older children and adolescents. When older
      children and adolescents are found to have iron deficiency, HP infection and
      other gastrointestinal pathologies should be ruled out before iron deficiency
      treatment.

PMID- 21728722
TI  - Helicobacter pylori infection-related pancytopenia in a young boy.

PMID- 21728723
TI  - Cerebral infarction in the setting of moyamoya in a pediatric patient with sickle
      beta+-thalassemia.

PMID- 21728724
TI  - Orthopedic implant approval: achieving the right balance.

PMID- 21728725
TI  - Translating epigenetics into an anticancer drug pipeline for solid tumors.

PMID- 21728727
TI  - Rationale, design and clinical performance of the Superion(r) Interspinous
      Spacer: a minimally invasive implant for treatment of lumbar spinal stenosis.
AB  - Lumbar spinal stenosis is a progressive degenerative condition that manifests as
      low back pain with neurogenic claudication as a cardinal clinical feature.
      Although mild radicular symptoms can often be successfully treated with
      conservative care, management of lumbar spinal stenosis grows increasingly
      difficult as symptoms worsen. No satisfactory nonsurgical treatments exist to
      manage moderate radicular symptoms and, therefore, these patients are faced with
      the decision of continuing ineffective conservative options or opting to undergo
      invasive decompressive spine surgery. The Superion((r)) Interspinous Spacer
      (Vertiflex, Inc., CA, USA) was developed specifically to fill the therapeutic
      void between conservative care and surgical decompression. The Superion device is
      a titanium implant that is delivered percutaneously and deployed between the
      spinous processes at the symptomatic vertebral levels. The Superion device
      improves radicular symptoms by limiting spinal extension and, consequently,
      minimizing impingement of neural and vascular elements. This article describes
      the rationale for and the design of the Superion device and summarizes initial
      clinical results with this novel, minimally invasive interspinous spacer.

PMID- 21728728
TI  - Wireless communication with implanted medical devices using the conductive
      properties of the body.
AB  - Many medical devices that are implanted in the body use wires or wireless
      radiofrequency telemetry to communicate with circuitry outside the body. However,
      the wires are a common source of surgical complications, including breakage,
      infection and electrical noise. In addition, radiofrequency telemetry requires
      large amounts of power and results in low-efficiency transmission through
      biological tissue. As an alternative, the conductive properties of the body can
      be used to enable wireless communication with implanted devices. In this article,
      several methods of intrabody communication are described and compared. In
      addition to reducing the complications that occur with current implantable
      medical devices, intrabody communication can enable novel types of miniature
      devices for research and clinical applications.

PMID- 21728729
TI  - The diagnostic value of multislice computed tomography in children with
      congenital lobar emphysema.
AB  - OBJECTIVE: To investigate the diagnostic value of multislice computed tomography
      (MSCT) in children with congenital lobar emphysema (CLE). MATERIALS & METHODS:
      Seven children with CLE diagnosed by surgery pathology had undergone thin-slice
      scanning of MSCT, multiplanar reconstruction and volume rendering technique. The
      diagnostic value of MSCT in children with CLE was evaluated. RESULTS: Among seven
      patients with CLE, three cases were located in the left upper lobe, two cases in
      the right upper lobe and two cases in the right middle-upper lobe. All cases were
      manifested by variable degrees of bronchus stenosis in the corresponding lung
      segment or lobe, increased lung radiolucence and volume, and reduced lung
      markings. In this group, there was one case, respectively, associated with left
      posterior mediastinal bronchogenic cyst, bronchiectasis in the right lung, a lung
      cyst in the right upper lobe, angiodysplasia in the right upper lung and
      congenital funnel chest; two cases of multiple lung bullae in the right lung,
      three cases of infection in both lungs and four cases of mediastinal hernia.
      CONCLUSION: MSCT and multidimensional reconstruction is a noninvasive diagnostic
      method that displays the location, degree and accompanying anomalies of CLE in
      three dimensions. It has significance for clinicians in that it reduces both
      misdiagnosis and the time taken to receive treatment.

PMID- 21728730
TI  - The role of active middle-ear implants in the rehabilitation of hearing loss.
AB  - The surgical implantation of auditory devices to improve or restore the sensation
      of hearing in affected individuals is a rapidly growing area of modern ear, nose
      and throat, and audiological practice. Following the enormous success of cochlear
      implantation and set to take an increasing role in the rehabilitation of deafness
      is the active middle-ear implant. They should be viewed as an alternative to
      conventional hearing aids for individuals who are either unable to wear hearing
      aids or reject them for a variety of reasons. This article discusses the
      different types of middle-ear implant that are currently in use and examines the
      significant challenges that remain to be overcome to further advance this field.

PMID- 21728731
TI  - New-generation diabetes management: glucose sensor-augmented insulin pump
      therapy.
AB  - Diabetes is one of the most common chronic disorders with an increasing incidence
      worldwide. Technologic advances in the field of diabetes have provided new tools
      for clinicians to manage this challenging disease. For example, the development
      of continuous subcutaneous insulin infusion systems have allowed for refinement
      in the delivery of insulin, while continuous glucose monitors provide patients
      and clinicians with a better understanding of the minute to minute glucose
      variability, leading to the titration of insulin delivery based on this
      variability when applicable. Merging of these devices has resulted in sensor
      augmented insulin pump therapy, which became a major building block upon which
      the artificial pancreas (closed-loop systems) can be developed. This article
      summarizes the evolution of sensor-augmented insulin pump therapy until present
      day and its future applications in new-generation diabetes management.

PMID- 21728732
TI  - Microneedle arrays as medical devices for enhanced transdermal drug delivery.
AB  - In order to exploit the transdermal route for systemic delivery of a wide range
      of drug molecules, including peptide/protein molecules and genetic material, a
      means of disrupting the excellent barrier properties of the uppermost layer of
      the skin, the stratum corneum, must be sought. The use of microneedle (MN) arrays
      has been proposed as a method to temporarily disrupt the barrier function of the
      skin and thus enable enhanced transdermal drug delivery. MN arrays consist of a
      plurality of micron-sized needles, generally ranging from 25 to 2000 um in
      height, of a variety of different shapes and composition (e.g., silicon, metal,
      sugars and biodegradable polymers). The application of such MN arrays to the skin
      results in the creation of aqueous channels that are orders of magnitude larger
      than molecular dimensions and, therefore, should readily permit the transport of
      macromolecules. This article will focus on recent and future developments for MN
      technology, focusing on the materials used for MN fabrication, the forces
      required for MN insertion and potential safety aspects that may be involved with
      the use of MN devices.

PMID- 21728733
TI  - Renaissance of contact x-ray therapy for treating rectal cancer.
AB  - Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation
      therapy technique to achieve local control and rectal preservation for early
      rectal adenocarcinoma. Despite these results, CXRT has not been used due to the
      shortage of the no longer manufactured Philips RT 50TM unit. Recently, a new CXRT
      machine (Papillon 50TM) became available on the market. This machine delivers a
      beam of 50 kV with a dose rate close to 15 Gy/min and has a percentage depth dose
      of 50% at 6-7 mm. The applicator size varies from 2-3 cm in diameter. Due to the
      original design of the main tube, treatment delivery is quick and more
      comfortable for the patients. An online viewing system incorporated in the tube
      allows a good visualization of the tumor with improved accuracy of radiation
      delivery. An international collaborative trial (Contact Endoscopic Microsurgery
      [CONTEM]) was set up to accrue approximately 300 cases of rectal adenocarcinoma
      staged T1, T2 or early T3 tumors in the UK, France, Denmark and Sweden. This
      trial should confirm the role of CXRT in curative treatment with organ
      preservation for early rectal cancers.

PMID- 21728734
TI  - Scientific evidence and principles for the use of endobronchial ultrasound and
      transbronchial needle aspiration.
AB  - Endobronchial ultrasound (EBUS), using the radial EBUS probe and convex-probe
      EBUS-guided transbronchial needle aspiration, are increasingly advocated for a
      wide array of minimally invasive thoracic procedures. The effectiveness of EBUS
      guided procedures has been demonstrated to a degree that, in many institutions,
      EBUS is becoming standard of practice for the diagnosis, staging and restaging of
      mediastinal lymphadenopathy in lung cancer, the diagnosis of sarcoidosis, and for
      bronchoscopic biopsy of peripheral lung lesions. Its role in other bronchoscopic
      procedures requires further study despite an already strong body of literature:
      diagnosis of lymphoma and benign infectious disease, diagnosis of early lung
      cancer and airway wall disorders, imaging of thoracic vascular disease such as
      pulmonary embolism, and therapeutic procedures such as placement of fiducial
      markers. In this article, we illustrate some of the principles of EBUS, describe
      major technical aspects pertaining to the procedure itself and provide a
      narrative review of original research addressing proposed roles of EBUS in a
      variety of indications. In closing, we describe future perspectives including new
      educational processes and philosophies that could favorably impact the rapid and
      safe dissemination of this evolving technology into clinical practice.

PMID- 21728735
TI  - Endovascular repair of thoracic aortic pathology.
AB  - Endovascular repair of thoracic aortic pathology is an evolving and increasingly
      attractive alternative to open repair. Endograft technology and delivery systems
      have improved rapidly since their introduction in the 1990s, and early and mid
      term results for currently available devices are promising. No individual device
      has proven to be superior as no comparative trials have been performed. However,
      each available device is unique in its characteristics to treat aortic disease:
      GORE((r)) TAG((r)) (WL Gore and Associates, AZ, USA), Zenith((r)) (TX1((r)) and
      TX2((r)), Cook, IN, USA), and TalentTM (Medtronic Vascular, CA, USA). In addition
      to a prerequisite set of endovascular skills, a detailed knowledge of different
      graft designs and an understanding of aortic pathology significantly affect the
      efficacy of endovascular repair of thoracic aortic disease. This article focuses
      on the currently available devices, their characteristics and pivotal clinical
      trial results.

PMID- 21728737
TI  - Perinatal outcomes in type 2 diabetic patients compared with non-diabetic
      patients matched by body mass index.
AB  - OBJECTIVE: Given that both type 2 diabetes and obesity are associated with
      adverse pregnancy outcomes and often coexist, we sought to determine if outcomes
      in type 2 diabetic patients are related to the presence of diabetes or to
      maternal obesity. METHODS: This retrospective cohort study examined perinatal
      outcomes of type 2 diabetic and nondiabetic patients matched by prepregnancy body
      mass index January 2000 to July 2008. Chi-square, Fisher's exact test, Mann
      Whitney U and t-tests were used to compare groups. The association between type 2
      diabetes and adverse perinatal outcomes was evaluated through logistic regression
      with adjustment for potential confounders. RESULTS: 213 pairs of type 2 and non
      diabetic patients were compared. Diabetic patients had overall worse composite
      pregnancy, delivery, fetal, and neonatal outcomes. Specifically, diabetic
      patients had higher rates of preeclampsia, poly- and oligohydramnios, cesarean
      delivery, shoulder dystocia, postpartum hemorrhage, preterm delivery, LGA infant,
      fetal anomaly, and neonatal hypoglycemia, hyperbilirubinemia, RDS, sepsis,
      intubation, and admission to the NICU. Diabetes remained a significant predictor
      of adverse delivery, fetal and neonatal composite outcomes when adjusted for
      confounders in logistic regression. CONCLUSIONS: Type 2 diabetic patients have a
      higher incidence of adverse perinatal outcomes than nondiabetic patients
      independent of obesity.

PMID- 21728738
TI  - Heavy prenatal alcohol exposure and risk of stillbirth and preterm delivery.
AB  - We prospectively identified 96 women consuming at least 4 drinks/day during
      pregnancy by screening 9628 pregnant women. In these women with heavy prenatal
      alcohol use, there were three stillbirths and one preterm delivery; 98 matched
      nondrinking women had no stillbirths and two preterm births. Preterm rates did
      not differ significantly. The stillbirth rate was higher in the exposed group (p
      = 0.06). Additional investigation showed the stillbirth rate in the exposed
      population (3.1%) was significantly higher (p = 0.019) than the reported Chilean
      population rate (0.45%). Our data suggest that heavy alcohol consumption may
      increase the risk for stillbirth but not preterm delivery.

PMID- 21728739
TI  - An original clinical methodology for non-invasive assessment of pivot-shift test.
AB  - Even if pivot-shift (PS) test has been clinically used to specifically detect
      anterior cruciate ligament (ACL) injury, the main problem in using this combined
      test has been yet associated with the difficulty of clearly quantifying its
      outcome. The goal of this study was to describe an original non-invasive
      methodology used to quantify PS test, highlighting its possible clinical
      reliability. The method was validated on 66 consecutive unilateral ACL-injured
      patients. A commercial triaxial accelerometer was non-invasively mounted on
      patient's tibia, the corresponding 3D acceleration was acquired during PS test
      execution and a set of specific parameters were automatically identified on the
      signal to quantify the test. PS test was repeated three times on both injured and
      controlateral limbs. Reliability of the method was found to be good (mean intra
      rater intraclass correlation coefficient was 0.79); moreover, we found that ACL
      deficient knees presented statistically higher values for the identified
      parameters--than the controlateral healthy limbs, averagely reporting also large
      effect size.

PMID- 21728741
TI  - The experience of Chinese physicians in the national health diplomacy programme
      deployed to Sudan.
AB  - Chinese Medical Teams have been working in developing countries since 1963 as a
      health diplomacy strategy. In 2010, 1252 Chinese medical personnel were assigned
      to 48 countries. We conducted a review of Chinese literature and governmental
      websites to describe the history and current distribution of Chinese Medical
      Teams around the world. In addition, we interviewed members of a 36-member
      Chinese Medical Team deployed to Sudan (primarily about their motivations to join
      the programme and the challenges and benefits they face), along with their
      Sudanese hosts. The most significant challenge health workers described was
      homesickness. Most members said they were able to maintain motivation through
      their curiosity and the doctor-friendly environment. All but two rated their own
      working performance as 'good' or 'very good', while their Sudanese colleagues
      consistently rated them even higher. Participants reported conflicting beliefs
      regarding the perceived responsibilities of the team and challenges around
      communication. Three pillars support the Chinese Medical Team programme in Sudan:
      bilateral government commitment, the professionalism of the Medical Teams, and
      the welcoming medical environment. Future success of this or similar Chinese
      programmes depend on the willingness of both governments to participate, the
      ongoing commitment of younger Chinese doctors, and the hospitality of physicians
      in the host country. There are also some threats to the programme, including a
      potentially diminishing need for Chinese doctors to support increasingly well
      trained host country physicians.

PMID- 21728742
TI  - Flavopiridol induces BCL-2 expression and represses oncogenic transcription
      factors in leukemic blasts from adults with refractory acute myeloid leukemia.
AB  - Flavopiridol is a cyclin-dependent kinase inhibitor that induces cell cycle
      arrest, apoptosis, and clinical responses in selected patients with acute myeloid
      leukemia (AML). A better understanding of the molecular pathways targeted by
      flavopiridol is needed to design optimal combinatorial therapy. Here, we report
      that in vivo administration of flavopiridol induced expression of the BCL-2 anti
      apoptotic gene in leukemic blasts from adult patients with refractory AML.
      Moreover, flavopiridol repressed the expression of genes encoding oncogenic
      transcription factors (HMGA1, STAT3, E2F1) and the major subunit of RNA
      Polymerase II. Our results provide mechanistic insight into the cellular pathways
      targeted by flavopiridol. Although further studies are needed, our findings also
      suggest that blocking anti-apoptotic pathways could enhance cytotoxicity with
      flavopiridol.

PMID- 21728743
TI  - Necrotizing myositis and septic shock caused by Haemophilus influenzae type f in
      a previously healthy man diagnosed with an IgG3 and a mannose-binding lectin
      deficiency.
AB  - An increased incidence of infections by Haemophilus influenzae type f (Hif) has
      recently been suggested, but such infections have mainly been regarded as
      opportunistic. We present here a dramatic case of Hif necrotizing myositis and
      septic shock. A subsequently diagnosed IgG3 and mannose-binding lectin deficiency
      possibly contributed to the severe outcome.

PMID- 21728744
TI  - Correlates of spontaneous clearance of hepatitis C virus in a Danish human
      immunodeficiency virus type 1 cohort.
AB  - BACKGROUND: Around a quarter of individuals infected with hepatitis C virus (HCV)
      are spontaneously able to clear the virus. Correlates of spontaneous HCV
      clearance are not well established and the aim of this study was to characterize
      factors associated with spontaneous HCV clearance in a human immunodeficiency
      virus (HIV)-co-infected cohort. METHODS: We analyzed 327 anti-HCV-positive HIV-1
      infected patients using multivariate logistic regression. HCV clearance was
      defined as the presence of anti-HCV with undetectable HCV RNA from at least 2
      measurements more than 6 months apart. RESULTS: We included 327 HIV-1-infected
      individuals, predominantly of Caucasian race; 112 (34%) were females, 258 (79%)
      were injecting drug users (IDU), 25 (8%) were men who have sex with men (MSM),
      and 20 (6%) were hepatitis B surface antigen (HBsAg)-positive. Seventy-six (23%;
      95% confidence interval (CI) 18-28) had cleared their HCV infection and 251 (77%;
      95% CI 72-82) had a chronic infection. The clearance rate in HBsAg-positive
      individuals was 65%. Being female, HBsAg-positive, or belonging to HIV exposure
      groups IDU and MSM predicted higher HCV clearance rates (adjusted odds ratio
      (aOR) 1.8, 95% CI 1-3.2; aOR 7.6, 95% CI 2.7-21; aOR 5.2, 1.2-23.5; and aOR 10.2,
      95% CI 1.8-58, respectively). Race, acquired immunodeficiency syndrome (AIDS),
      and antiretroviral therapy were not associated with HCV clearance. CONCLUSIONS:
      The HCV clearance rate in this HIV-1 cohort was 23%. MSM and IDUs may have higher
      clearance rates due to their repeated exposure to low-dose HCV, leading to immune
      memory. Our data suggest an interaction of hepatitis B virus and HCV that
      influences the outcome of acute HCV infection.

PMID- 21728745
TI  - Colonization of pressure ulcers by multidrug-resistant microorganisms in patients
      receiving home care.
AB  - Colonization and/or infection with multidrug-resistant microorganisms (MDRO) of
      pressure ulcers in patients receiving care at home have seldom been investigated.
      The objective of this study was to assess the prevalence of MDRO colonization in
      pressure ulcers of patients receiving home care in Palermo, Italy. Vancomycin
      resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA),
      and multidrug-resistant Gram-negative bacilli (MDRGN) were isolated, identified,
      and characterized from pressure ulcers and selected home environment surfaces.
      Thirty-two patients were enrolled, of whom 12 were under antimicrobial therapy.
      Five patients had been admitted to hospital in the preceding year. Nineteen
      patients tested positive for 1 or more MDROs. In particular, 1 patient was
      colonized by a vanA-containing strain of VRE, 5 by MRSA, and 17 by MDRGN of
      different species. Our findings suggest that pressure ulcers in home care
      patients could play a role in bringing MDROs into the community setting.

PMID- 21728746
TI  - Professional confidence: a concept analysis.
AB  - INTRODUCTION: Professional confidence is a concept that is frequently used and or
      implied in occupational therapy literature, but often without specifying its
      meaning. METHOD: Rodgers's Model of Concept Analysis was used to analyse the term
      "professional confidence". Published research obtained from a federated search in
      four health sciences databases was used to inform the concept analysis. RESULTS:
      The definitions, attributes, antecedents, and consequences of professional
      confidence as evidenced in the literature are discussed. Surrogate terms and
      related concepts are identified, and a model case of the concept provided. Based
      on the analysis, professional confidence can be described as a dynamic, maturing
      personal belief held by a professional or student. This includes an understanding
      of and a belief in the role, scope of practice, and significance of the
      profession, and is based on their capacity to competently fulfil these
      expectations, fostered through a process of affirming experiences. DISCUSSION:
      Developing and fostering professional confidence should be nurtured and valued to
      the same extent as professional competence, as the former underpins the latter,
      and both are linked to professional identity.

PMID- 21728747
TI  - Application of mercury intrusion porosimetry for studying the porosity of mineral
      trioxide aggregate at two different pH.
AB  - OBJECTIVE: To evaluate a novel method of detecting and comparing the porosity of
      white Mineral Trioxide Aggregate and Portland cement at two different pH.
      MATERIALS AND METHODS: Cylindrical specimens (n = 120) were prepared from
      hydrated ordinary white Portland Cement (WPC) (n = 60) and white Mineral Trioxide
      Aggregate (WMTA) (n = 60) and exposed to environments with pH of 4.4 (n = 30) or
      7.4 (n = 30). The pore size distribution and total pore volume were detected
      using Mercury Intrusion Porosimetry. Data were analyzed by analysis of variance
      and post-hoc Tukey or Tamhane test (p = 0.05). RESULTS: The pore volume of WMTA
      was significantly lesser than WPC at both pH (p < 0.05). The surface tension of
      mercury was taken as 480 (N/m) and the contact angle 141.3 degrees  for both
      materials. Pores were consistently found in all specimens. Total pore volumes for
      WPC and WMTA (cubic centimeter/gram) were 0.1954 and 0.1023, respectively, while
      the diameter of the pores ranged from 50-100 A and 20-50 A, respectively.
      CONCLUSIONS: Mercury Intrusion Porosimetry technique is a promising and reliable
      technique for assessing the porosity of endodontic materials.

PMID- 21728748
TI  - Correlation of splint therapy outcome with the electromyography of masticatory
      muscles in temporomandibular disorder with myofascial pain.
AB  - OBJECTIVES: The aim of this study was to assess the effect of occlusal splint
      therapy on the electromyographic amplitude records (MUV) of masticatory muscles
      in temporomandibular disorder (TMD) with myofascial pain and to detect a possible
      existence of a relationship between this effect and the treatment outcome.
      MATERIALS AND METHODS: Forty patients (23 females and 17 males) having TMD with
      myofascial pain were included in this study. They were randomly divided into two
      equal groups (20 of each). The first group (A) was treated by occlusal splints
      for 6 months while the second group (B) acted as a control. A clinical assessment
      and surface electromyography (EMG) for the masticatory muscles were performed at
      the beginning of the study, then 6 months later. The collected data were
      statistically analyzed using paired t-test. The differences were considered
      significant at p < 0.05. RESULTS: The results showed that 85% of group A either
      completely recovered (35%) or clinically improved (50%) while only 20% of group B
      had a spontaneous improvement. In group A, the means of the electromyographic
      amplitude records (MUV) of the monitored muscles have decreased after 6 months.
      However, the decrease was statistically insignificant (p > 0.05) in the patients
      (15%) who had no clinical changes. In group B, the means of the muscles' records
      (MUV) in the left side slightly increased while those of the right side slightly
      decreased. These changes were statistically insignificant (p > 0.05).
      CONCLUSIONS: Occlusal splint could eliminate or improve the signs and symptoms of
      TMD patients with myofascial pain. It reduces the electromyographic amplitude
      records (MUV) of the masticatory muscles. The splint therapy outcome has a
      correlation with the electromyographic amplitude changes of the masticatory
      muscles.

PMID- 21728749
TI  - Perioperative complications after translabyrinthine removal of large or giant
      vestibular schwannoma: outcomes for 123 patients.

PMID- 21728750
TI  - Late nodal metastasis of T2 oral cancer can be reduced by a combination of
      preoperative ultrasonographic examination and frozen section biopsy during
      supraomohyoid neck dissection.
AB  - CONCLUSION: The occult metastasis rate for T2 oral cancer can be reduced by
      ultrasonography (US). Also, the late metastasis rate is considered to be reduced
      by combining US with frozen section biopsy (FSB) during supraomohyoid neck
      dissection (SOHND). OBJECTIVES: Early oral cancer has been reported to show
      occult metastases in 15-53% of patients, but the criteria or methods for the
      diagnosis of cervical lymph node metastasis are unclear in many studies, and
      there is no clear definition of occult metastasis. In patients with T2 oral
      cancer, the diagnosis of lymph node metastasis by US and its pathological
      diagnosis (pN) after neck dissection were compared to evaluate the usefulness and
      limitations of US, occult metastasis rate, significance of SOHND as preventive
      neck dissection, and use of FSB. METHODS: A total of 73 patients with T2 oral
      cancer were investigated retrospectively. Modified radical neck dissection (MRND)
      was performed in N+ patients, and SOHND was carried out in N0 patients. FSB was
      performed in all patients undergoing SOHND. US and pN diagnoses were compared.
      RESULTS: The occult metastasis rate was 18% when occult metastases were limited
      to those detected by SOHND and 22% when late nodal recurrences were also
      included.

PMID- 21728751
TI  - Recurrence of vertigo in patients with vestibular neuritis.
AB  - CONCLUSION. The recurrence rate of vertigo due to any cause in patients with
      vestibular neuritis (VN) was about 26.0% in our study. No clinical
      characteristics were significantly associated with recurrences. OBJECTIVE: We
      aimed to: 1) determine the prevalence of recurrent VN; 2) compare the clinical
      characteristics and epidemiologic factors of patients with non-recurrent and
      recurrent VN; and 3) determine the prevalence of benign paroxysmal positional
      vertigo (BPPV) in patients with VN. METHODS: In 131 patients diagnosed as having
      VN (68 males, aged 49.8 +/- 14.9 years and 63 females, aged 57.5 +/- 12.5 years),
      a retrospective chart review and telephone survey about the recurrent vertigo
      were performed. Vestibular function testing, inner ear magnetic resonance imaging
      (MRI), and pure tone audiograms were performed on every patient. Vestibular
      function testing was repeated in patients with recurrences. RESULTS: Fourteen of
      131 patients (10.7%) had recurrent VN. The subjective intensity of recurrent VN
      was less than the first attack. There were no significant differences in clinical
      characteristics such as accompanying headache or preceding respiratory infection
      and in epidemiologic risk factors between patients with recurrent and non
      recurrent VN. Twenty of 131 patients (15.3%) experienced BPPV during the follow
      up period.

PMID- 21728752
TI  - Different cortical metabolic activation by visual stimuli possibly due to
      different time courses of hearing loss in patients with GJB2 and SLC26A4
      mutations.
AB  - CONCLUSION: We have demonstrated differences in cortical activation with language
      related visual stimuli in patients who were profoundly deafened due to genetic
      mutations in GJB2 and SLC26A4. The differences in cortical processing patterns
      between these two cases may have been influenced by the differing clinical
      courses and pathogenesis of hearing loss due to genetic mutations. Our results
      suggest the importance of hearing during early childhood for the development of a
      normal cortical language network. OBJECTIVES: To investigate the cortical
      activation with language-related visual stimuli in patients who were profoundly
      deafened due to genetic mutations in GJB2 and SLC26A4. METHODS: The cortical
      activity of two adult patients with known genetic mutations (GJB2, SLC26A4) was
      evaluated with fluorodeoxyglucose-positron emission tomography (FDG-PET) with a
      visual language task and compared with that of normal-hearing controls. RESULTS:
      A patient with a GJB2 mutation showed activation in the right auditory
      association area [BA21, BA22], and the left auditory association area [BA42] even
      with visual language task; in contrast, a patient with an SLC26A4 mutation showed
      no significant activation in the corresponding area.

PMID- 21728753
TI  - Fructose-bisphosphate aldolase and pyruvate kinase, two novel immunogens in
      Madurella mycetomatis.
AB  - Eumycetoma, a chronic granulomatous disease characterized by a subcutaneous mass,
      multiple sinuses and purulent discharge containing grains, remains difficult to
      diagnose and treat. Madurella mycetomatis is the most common causative agent of
      eumycetoma. Using a serum pool from patients with active mycetoma, we screened a
      M. mycetomatis-specific lambdagt11 cDNA library which was shown to contain 8% of
      cDNA inserts encoding proteins involved in glycolysis. Two of these enzymes,
      fructose-bisphosphate aldolase (FBA) and pyruvate kinase (PK), were produced in
      vitro and their antigenicity was studied with bead-based flow cytometry. It
      appeared that both FBA and PK IgG antibodies were present in eumycetoma patient
      sera. However, only FBA antibody levels were found to be significantly higher in
      eumycetoma patient sera when compared to healthy Sudanese controls. Furthermore,
      FBA and PK were also found to be expressed on the hyphae present in the mycetoma
      grain. In conclusion, this study presents two new antigenic proteins of M.
      mycetomatis next to the translationally controlled tumour protein (TCTP): the
      glycolytic enzymes FBA and PK. These antigens might be useful as vaccine
      candidates in the prevention of mycetoma.

PMID- 21728754
TI  - Identification of a metallopeptidase with TOP-like activity in Paracoccidioides
      brasiliensis, with increased expression in a virulent strain.
AB  - Paracoccidioidomycosis (PCM), caused by the pathogenic fungus Paracoccidioides
      brasiliensis, is a systemic mycosis with severe acute and chronic forms. The
      pathology of PCM is not completely understood, and the role of proteases in the
      infection is not clearly defined. In this report, we describe a metallopeptidase
      activity in P. brasiliensis total and cytosolic protein extracts similar to that
      of mammalian thimet oligopeptidase (TOP). The analogous enzyme was suggested by
      analysis of P. brasiliensis genome databank and by hydrolytic activity of the
      FRET peptide Abz-GFSPFRQ-EDDnp which was completely inhibited by o-phenanthrolin
      and significantly inhibited by the TOP inhibitor, JA-2. This activity was also
      partially inhibited by IgG purified from patients with PCM, but not from normal
      individuals. As shown by high-performance liquid chromatography (HPLC), the
      hydrolysis of bradykinin had the same pattern as that of mammalian TOP, and anti
      mammalian TOP antibodies significantly inhibited fungal cytosolic peptidase
      activity. Moreover, anti-mammalian TOP antibodies recognized a component of 80
      kDa on fungal cytosol. A P. brasiliensis virulent isolate showed higher gene
      expression and TOP-like peptidase activity than a non-virulent strain. The
      release of enzyme following fungal lysis would be consistent with host antibody
      production and may have a role in the pathogenesis, inflammation and further
      development of the mycosis.

PMID- 21728755
TI  - Characterization of the Candida parapsilosis complex in East China: species
      distribution differs among cities.
AB  - Candida parapsilosis, which was previously considered to be a complex of three
      genetically distinct groups, has emerged as a significant agent of nosocomial
      infections. Recently, this complex was separated into three species: C.
      parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis. In China, data
      pertaining to these fungi are limited. In this study, we examined 57 isolates of
      members of the C. parapsilosis complex collected from four cities in East China,
      i.e., Nanjing (n = 22), Nanchang (n = 20), Shanghai (n = 12) and Jinan (n = 3).
      C. parapsilosis sensu stricto represented 71.9% of all isolates, while C.
      metapsilosis accounted for the remaining 28.1%. C. orthopsilosis could not be
      identified. A significantly high prevalence of C. metapsilosis was observed in
      strains recovered from Nanchang, 60% (12/20) of the isolates were C.
      metapsilosis. Sequence analysis of internal transcribed spacer region revealed
      two unevenly distributed genotypes among the C. metapsilosis strains. A PCR
      restriction fragment length polymorphism assay was described for rapid
      identification. The strains were susceptible to fluconazole, voriconazole,
      amphoterincin B and micafungin. Six (15%) isolates of C. parapsilosis sensu
      stricto and three (18.8%) of C. metapsilosis were found to be dose-dependent
      susceptible to itraconazole. C. parapsilosis sensu stricto strains were less
      susceptible to micafungin than C. metapsilosis.

PMID- 21728756
TI  - Review of the epidemiologic literature on residential exposure to
      perchloroethylene.
AB  - Perchloroethylene is a solvent that is widely used for dry cleaning. There has
      been considerable interest in the toxicity of this chemical because of the
      potential for low-level exposure among a large portion of the US population.
      Although substantial epidemiologic literature exists on high-level occupational
      exposure to perchloroethylene, there are relatively few studies dealing with
      lower-level residential exposure. In the current paper, the author reviews this
      limited residential literature, with special emphasis on strengths, limitations,
      and consistency. Reviewed studies primarily address neurobehavioral, cancer, and
      reproductive endpoints. Most studies used an ecological or cross-sectional
      design, with exposure defined by either drinking-water contamination or proximity
      to dry cleaning. In general, reviewed studies were highly exploratory, with
      inconsistencies and potential for bias that detract from interpretation of study
      findings. The magnitudes of reported effects are frequently incompatible with the
      effects reported from much higher occupational and human-chamber exposures.
      Overall, few reliable conclusions can be drawn from this sparse and highly
      limited body of literature.

PMID- 21728759
TI  - The autophagy-inducing drug carbamazepine is a radiation protector and mitigator.
AB  - PURPOSE: To determine whether Carbamazepine (CBZ) is a radiation protector and/or
      mitigator. MATERIALS AND METHODS: Murine hematopoietic progenitor 32D cl 3 cells
      were incubated in 1, 10, or 100 MUM CBZ 1 h before or immediately after 0-8 Gy
      irradiation and assayed for clonogenic survival. Autophagy was assayed by
      immunoblot for microtubule-associated protein light chain 3 (LC3). In vivo
      radioprotection and mitigation were determined with C57BL/6NTac mice. RESULTS:
      CBZ treatment at 1, 10 or 100 MUM for 1 h prior to irradiation increased
      radioresistance (the dose for 37% survival or D(0)) from control 1.5 +/- 0.1 Gy
      to 2.1 +/- 0.2 Gy (P = 0.012), 2.3 +/- 0.1 Gy (P = 0.010), and 3.6 +/- 0.7 Gy (P
      = 0.003), respectively; after irradiation increased the extrapolation number (n)
      from 1.5 +/- 0.3 to 10.1 +/- 4.2 (P = 0.011), 5.5 +/- 1.7 (P = 0.019), and 3.6 +/
      0.8 (P = 0.014), respectively, and increased autophagy. CBZ treated mice 10 min
      or 24 h before or 10 min or 12 h after 9.25 Gy total body irradiation (TBI)
      showed increased survival (P = 0.012, 0.011, 0.0002, and 0.017, respectively).
      CONCLUSION: CBZ may be a useful radiation protector and mitigator.

PMID- 21728761
TI  - Abstracts of the Annual Conference of the British Association of Sport and
      Exercise Sciences (BASES) 2008. September 2-4, 2008. Brunel, United Kingdom.

PMID- 21728760
TI  - Solid lipid nanoparticles and nanosuspension formulation of Saquinavir:
      preparation, characterization, pharmacokinetics and biodistribution studies.
AB  - Solid lipid nanoparticles (SLNs) and nanosuspensions (NSs) have shown great
      promise for improving bioavailability of poorly water-soluble drugs. This study
      was aimed to develop SLNs and NS of Saquinavir (SQ) for improvement in
      bioavailability. These formulations were characterized and their pharmacokinetics
      and biodistribution in mice were evaluated. Saquinavir-loaded SLNs (SQSLNs)
      showed particle size 215 +/- 9 nm and entrapment efficiency 79.24 +/- 1.53%,
      while solid-state studies (differential scanning calorimetry and X-ray
      diffraction) indicated entrapment of the drug in SLNs. Saquinavir NS (SNS) showed
      particle size 344 +/- 16 nm with fourfold increase in saturation solubility and
      its solid-state studies showed reduction in crystallinity. Pharmacokinetics and
      biodistribution studies of orally administered SQSLN and SNS in mice exhibited
      higher plasma level concentration compared to saquinavir microsuspension (SMS).
      The relative bioavailabilities for SNS and SQSLN were 37.39% and 66.53%,
      respectively, compared to 18.87% bioavailability obtained after administration of
      SMS, indicating suitability of nanoparticulate formulations for improving
      bioavailability.

PMID- 21728762
TI  - E-solutions in bioanalysis.

PMID- 21728763
TI  - Getting from proto-sharing to sharing: collaborating on electronic solutions for
      ligand-binding assays.

PMID- 21728764
TI  - Regulated bioanalytical laboratory automation: where we came from, where we are
      and where we are going.

PMID- 21728765
TI  - Benefits of an automated GLP final report preparation software solution.
AB  - The final product of analytical laboratories performing US FDA-regulated (or GLP)
      method validation and bioanalysis studies is the final report. Although there are
      commercial-off-the-shelf (COTS) software/instrument systems available to
      laboratory managers to automate and manage almost every aspect of the
      instrumental and sample-handling processes of GLP studies, there are few software
      systems available to fully manage the GLP final report preparation process. This
      lack of appropriate COTS tools results in the implementation of rather Byzantine
      and manual processes to cobble together all the information needed to generate a
      GLP final report. The manual nature of these processes results in the need for
      several iterative quality control and quality assurance events to ensure data
      accuracy and report formatting. The industry is in need of a COTS solution that
      gives laboratory managers and study directors the ability to manage as many
      portions as possible of the GLP final report writing process and the ability to
      generate a GLP final report with the click of a button. This article describes
      the COTS software features needed to give laboratory managers and study directors
      such a solution.

PMID- 21728766
TI  - Addressing the heterogeneous IT landscape of bioanalytical laboratories to
      increase efficiency of regulatory reporting and data analysis.
AB  - Modern bioanalytical laboratories are operating heterogeneous IT systems to
      satisfy process-related data capturing and processing. Whenever a cross-system
      perspective is desirable, for example, to answer 'quality-by-design'-related
      questions or populate submission documents, manual processes dominate these
      organizations. This article discusses the origin of this situation and the
      typical approach as well as a state-of-the-art approach to resolve cross-system
      obstacles.

PMID- 21728768
TI  - Young Investigator: David J R Conroy.

PMID- 21728769
TI  - Utilization of electronic resources in the NDA/BLA regulatory review of
      bioanalytical data: perspectives from US FDA reviewers.
AB  - The electronic common technical document (eCTD) format is frequently used in
      submitting bioanalytical information as part of a new drug application (NDA) or
      biologics license application (BLA). While the use of the eCTD format has many
      advantages, the potential for further improvement exists. This review highlights
      issues that are commonly encountered in reviewing bioanalytical information
      during the review process. In addition, the authors suggest potential strategies
      that illustrate how the ability to locate bioanalytical data or information can
      be enhanced and the summary information can be more consistently organized for a
      NDA or a BLA that is submitted in an eCTD format.

PMID- 21728770
TI  - Conducting remote bioanalytical data monitoring and review based on scientific
      quality objectives.
AB  - For bioanalytical laboratories that follow GLP regulations and generate data for
      new drug filing, ensuring quality standards set by regulatory guidance is a
      fundamental expectation. Numerous guidelines and White Papers have been published
      by regulatory agencies, professional working groups and field experts in the past
      two decades, and have significantly improved the standards of good practices for
      bioanalysis. From a sponsor's perspective, continuous quality monitoring of the
      data generated by CRO laboratories, identifying adverse trends and taking
      corrective and preventative actions against issues encountered, are critical
      aspects of effective bioanalytical outsourcing management. This is especially
      important for clinical bioanalysis, where one validated assay is applied for
      analyzing a large number of samples of diverse demographics and disease states.
      This perspective article presents thoughts toward remote data monitoring and its
      merits for scientific quality oversight, and introduces a novel Bioanalytical
      Data Review software that was custom-developed and platform-neural, to conduct
      remote data monitoring on raw or processed LC-MS/MS data from CROs. Flexible,
      adaptive and user-customizable queries are applied for conducting project-, batch
      and sample-level data review based on scientific quality performance factors
      commonly assessed for good bioanalytical practice.

PMID- 21728771
TI  - Automated reporting of pharmacokinetic study results: gaining efficiency
      downstream from the laboratory.
AB  - The purpose of bioanalysis in the pharmaceutical industry is to provide 'raw'
      data about the concentration of a drug candidate and its metabolites as input for
      studies of drug properties such as pharmacokinetic (PK), toxicokinetic,
      bioavailability/bioequivalence and other studies. Building a seamless workflow
      from the laboratory to final reports is an ongoing challenge for IT groups and
      users alike. In such a workflow, PK automation can provide companies with the
      means to vastly increase the productivity of their scientific staff while
      improving the quality and consistency of their reports on PK analyses. This
      report presents the concept and benefits of PK automation and discuss which
      features of an automated reporting workflow should be translated into software
      requirements that pharmaceutical companies can use to select or build an
      efficient and effective PK automation solution that best meets their needs.

PMID- 21728772
TI  - Challenges in archiving electronic bioanalytical data supporting GLP studies in a
      CRO.
AB  - The purpose of this article is to articulate the fundamental issues of archiving
      electronic GLP data in a CRO environment. CROs struggle to address the absolute
      requirement of archiving GLP studies electronically. The difficulty of adhering
      to this is partly due to the wide variety of systems and types of electronic
      data. Often the end solution to this complicated issue is printing the data at
      the end of the study and in turn archiving the paper data, foregoing or ignoring
      the fact that scientific decisions were made while reviewing electronic data.
      Paper data and electronic data can be different. For example, chromatographic
      resolution or being able to focus in on detailed integration of chromatograms can
      significantly change the perspective of the data. While the core goal of
      archiving according to GLP principles are met, the reality is much different.
      Businesses purchasing CRO capabilities and regulatory agencies have been quite
      clear that when it comes to auditing the data that the electronic record is the
      preferred and often required source of the information for auditing and review
      purposes. The fact is that paper data do not always provide the flexibility,
      sensitivity and complete data context that an electronic record can provide. The
      ability to adhere to compliance standards due to the electronic data cannot be
      undervalued and by printing the data after all the acquisition, decisions,
      scientific judgments and review, do a complete disservice to the multidimensional
      (such as colors for deactivated or changed data, audit trails, 'zooming-in
      functionality', direct data links and snapshots) data in an electronic system.

PMID- 21728773
TI  - Cost-effective and business-beneficial computer validation for bioanalytical
      laboratories.
AB  - Computerized system validation is often viewed as a burden and a waste of time to
      meet regulatory requirements. This article presents a different approach by
      looking at validation in a bioanalytical laboratory from the business benefits
      that computer validation can bring. Ask yourself the question, have you ever
      bought a computerized system that did not meet your initial expectations? This
      article will look at understanding the process to be automated, the paper to be
      eliminated and the records to be signed to meet the requirements of the GLP or
      GCP and Part 11 regulations. This paper will only consider commercial
      nonconfigurable and configurable software such as plate readers and LC-MS/MS data
      systems rather than LIMS or custom applications. Two streamlined life cycle
      models are presented. The first one consists of a single document for validation
      of nonconfigurable software. The second is for configurable software and is a
      five-stage model that avoids the need to write functional and design
      specifications. Both models are aimed at managing the risk each type of software
      poses whist reducing the amount of documented evidence required for validation.

PMID- 21728774
TI  - Impact of the implementation of a well-designed electronic laboratory notebook on
      bioanalytical laboratory function.
AB  - This paper shares experiences of the Bristol-Myers Squibb Company during the
      design, validation and implementation of an electronic laboratory notebook (ELN)
      into the GLP/regulated bioanalytical analysis area, as well as addresses the
      impact on bioanalytical laboratory functions with the implementation of the
      electronic notebook. Some of the key points covered are: knowledge management -
      the project-based electronic notebook takes full advantage of the available
      technology that focuses on data organization and sharing so that scientific data
      generated by individual scientists became department knowledge; bioanalytical
      workflows in the ELN - the custom-built workflows that include data entry
      templates, validated calculation processes, integration with laboratory
      information management systems/laboratory instruments, and reporting capability
      improve the data quality and overall workflow efficiency; regulatory compliance -
      carefully designed notebook reviewing processes, cross referencing of distributed
      information, audit trail and software validation reduce compliance risks. By
      taking into consideration both data generation and project documentation needs, a
      well-designed ELN can deliver significant improvements in laboratory efficiency,
      work productivity, and regulatory compliance.

PMID- 21728775
TI  - The six critical attributes of the next generation of quality management software
      systems.
AB  - Driven by both the need to meet regulatory requirements and a genuine desire to
      drive improved quality, quality management systems encompassing standard
      operating procedure, corrective and preventative actions and related processes
      have existed for many years, both in paper and electronic form. The impact of
      quality management systems on 'actual' quality, however, is often reported as far
      less than desired. A quality management software system that moves beyond formal
      forms-driven processes to include a true closed loop design, manage disparate
      processes across the enterprise, provide support for collaborative processes and
      deliver insight into the overall state of control has the potential to close the
      gap between simply accomplishing regulatory compliance and delivering measurable
      improvements in quality and efficiency.

PMID- 21728777
TI  - Association between The Family Nutrition and Physical Activity Screening Tool and
      cardiovascular disease risk factors in 10-year old children.
AB  - OBJECTIVE: To examine the association of the Family Nutrition and Physical
      Activity (FNPA) screening tool with cardiovascular disease (CVD) risk factors in
      10-year old children. METHODS: A total of 119 children were assessed for body
      mass index (BMI), percent body fat, waist circumference, total cholesterol, high
      density lipoprotein-cholesterol (HDL), and resting blood pressure. A continuous
      CVD risk score was created using total cholesterol to HDL-cholesterol ratio
      (TC:HDL), mean arterial pressure (MAP), and waist circumference. The FNPA survey
      was completed by parents. RESULTS: The FNPA score was significantly correlated
      with adiposity measures (r = ?0.35 to ?0.43) and the continuous CVD risk score (r
      = ?0.22) (p < 0.05) but not with TC:HDL or MAP. The prevalence of overweight and
      obese (43.1% vs. 14.9%) and the mean values for BMI (20.3 ? 4.3 vs. 18.0 ? 2.7
      kg/m(2)) and percent body fat (24.8 ? 8.3% vs. 20.1 ? 5.7%) were significantly
      higher in children with a FNPA score ? 25 when compared to those with a FNPA
      score > 25 (median split) (p < 0.05). The continuous CVD risk score was not
      significantly different between these two groups. Overweight and obese children
      had a significantly lower mean FNPA score when compared to normal weight
      children. CONCLUSION: Children from a high-risk, obesogenic family environment
      (determined using the FNPA) have a higher level of adiposity and CVD risk factor
      profile than children from a low-risk family environment. The FNPA screening tool
      can help identify children that may be at risk for overweight and adverse CVD
      risk factor development.

PMID- 21728778
TI  - Does child weight influence how mothers report their feeding practices?
AB  - OBJECTIVES: The present study aimed to ascertain whether parental reports of
      their feeding practices are associated with independent observations of these
      behaviours, and whether the reliability of maternal report depends upon the
      child's weight. METHODS: A total of 56 mothers and their children ate a lunch to
      satiety which was videotaped and coded for maternal use of control during
      feeding. Mothers also completed questionnaires about their feeding practices and
      children were weighed and measured. RESULTS: Maternal reports of controlling
      feeding practices were poorly related to independent observations of these
      behaviours in the laboratory. However, there was a significant interaction
      between child BMI z score and observed pressure to eat in predicting maternally
      reported pressure to eat. There was also a significant interaction between child
      BMI z score and observed maternal restriction with food in predicting maternally
      reported restriction. When decomposed, these interactions suggested that only
      mothers of relatively underweight children were accurate at reporting their use
      of pressure to eat when compared to independent observations. For mothers of
      relatively overweight children there was a significant negative relationship
      between observed and reported restriction over food. CONCLUSIONS: Overall there
      was poor correspondence between maternal reports and independent observations of
      the use of controlling feeding practices. Further research is needed to replicate
      these findings and to ascertain whether parents who are inaccurate at reporting
      their use of these feeding practices are unaware that they are using controlling
      feeding practices or whether they are responding in socially desirable ways to
      questionnaires assessing their feeding behaviour.

PMID- 21728779
TI  - Effect of extremely high specific flow rates on the removal of NOM and arsenic
      from groundwater with an ion-exchange resin: a pilot-scale study in Northern
      Serbia.
AB  - A pilot-scale study was performed to explore the possibility of the removal of
      natural organic matter (NOM) and arsenic from groundwater in the village of
      Melenci (Northern Serbia) using strongly basic, macroporous ion-exchange resin,
      commercially available as Amberlite IRA 958-Cl. The influences of the specific
      flow rate (SFR) and a broad range of contact times were studied using native
      groundwater and the same water pretreated with sodium hypochlorite (NaClO) for
      the oxidation of As(III) to As(V) and the degradation of NOM. The investigated
      SFR exceeded the manufacturer's recommended maximum value by up to ten times. In
      the range of SFR from 50 to 300 bed volumes per hour (BV/h), a higher efficiency
      of NOM removal was achieved in the absence of the oxidant, whereas at lower SFR
      and shorter contact times, the efficiency was higher when the water was
      pretreated. The arsenic removal from the oxidant-pretreated water was equally
      efficient at all SFR, whereas in the absence of the oxidant the efficiency was
      significantly lower and did not depend on SFR. The effectiveness of the resin
      illustrates the fact that the experimentally determined optimum SFR value of 30
      BV/h is stated as the maximum in the manufacturer's specifications.

PMID- 21728780
TI  - Asking mom: formative research for an HPV vaccine campaign targeting mothers of
      adolescent girls.
AB  - Vaccination against the types of human papillomavirus (HPV) that cause about 70%
      of cervical cancers is approved for use in girls and women between 9 and 26 years
      of age and recommended routinely in 11-12-year-old girls. This article reports on
      the systematic theory-based formative research conducted to develop HPV vaccine
      messages for a campaign targeting racially diverse mothers of nonvaccinated 11-12
      year-old girls in rural Southeastern United States. A consortium of 13 county
      health departments concerned about high rates of cervical cancer in their region
      relative to state and national averages initiated the campaign. The research
      examined behavioral determinants for vaccination decisions as well as mothers'
      reactions to message frames and emotional appeals. On the basis of focus groups
      and intercept interviews (n = 79), the authors demonstrated how preproduction
      message research and production message testing were used to develop messages
      that would motivate mothers of preteen girls. Core emotional truths that emerged
      were a mother's instinct to protect her daughter from harm and to embrace
      aspirations for her daughter's future. Mothers also reacted more positively to
      text about preventing cervical cancer than about preventing HPV, a sexually
      transmitted disease. Mothers preferred message concepts with photos of minorities
      and Caucasian mothers and daughters.

PMID- 21728781
TI  - Midwives' cell phone use and health knowledge in rural communities.
AB  - This study developed and tested a theoretical model that explains the underlying
      process through which the use of cell phones can facilitate the capacity of
      community health care workers in developing regions. On the basis of a study
      conducted on 223 midwives in rural regions of Indonesia, the results showed that
      cell phone use was positively associated with midwives' access to institutional
      and peer information resources. Access to institutional resources was positively
      associated with midwives' health knowledge. Further, access to peer resources was
      associated with higher self-efficacy, which was positively associated with health
      knowledge. The study provides implications for technology intervention strategies
      targeted to community health workers in rural communities.

PMID- 21728782
TI  - The Swedish validation of Edinburgh Postnatal Depression Scale (EPDS) during
      pregnancy.
AB  - BACKGROUND: Around 10-15% of women suffer from depressive illness during
      pregnancy or the first year postpartum. Depression during pregnancy constitutes a
      risk for prenatal stress and preterm birth. No validated screening instrument for
      detecting depression during pregnancy was available in Swedish. AIMS: We aimed to
      validate the Edinburgh Postnatal Depression Scale (EPDS) against DSM-IV criteria
      for depression during pregnancy, establish a reliable cut-off and estimate the
      correlation between the EPDS and HAD-S (Hospital Anxiety and Depression Scale).
      METHODS: In a population-based community sample of 1175 pregnant women, 918 women
      (78%) answered questionnaires with the EPDS and HAD-S. In all, 121 were
      interviewed using the PRIME-MD (Primary Care Evaluation of Mental disorders) for
      diagnosing depression. Women were interviewed in mean gestational week 13 (range
      8-21). For the EPDS, a receiver operating characteristic (ROC) curve was
      calculated for prediction of depression. Pearson's correlation coefficient was
      used to investigate the association between EPDS and HAD-S scores. RESULTS: The
      optimal cut-off score on the EPDS scale for detecting depression was >=13
      (standard error coefficient of 1.09 and c-statistics of 0.84) giving a
      sensitivity of 77% and specificity of 94%. The EPDS scores correlated strongly
      with the HAD-S, Pearson's correlation was 0.83 (P < 0.0001). CONCLUSIONS: This
      study confirms that the EPDS is a valid screening instrument for detection of
      depressive symptoms during pregnancy. The EPDS shows persuasive measuring
      outcomes with an optimal cut-off at >=13. CLINICAL IMPLICATIONS: Healthcare for
      pregnant women should consider screening procedures and follow-up routines for
      depressive symptoms.

PMID- 21728783
TI  - Factors associated with the course of symptoms in bipolar disorder during a 1
      year follow-up: depression vs. sub-threshold mixed state.
AB  - BACKGROUND: Mixed mood states, even in their sub-threshold forms, may
      significantly affect the course and outcome of bipolar disorder (BD). AIM: To
      compare two samples of BD patients presenting a major depressive episode and a
      sub-threshold mixed state in terms of global functioning, clinical outcome,
      social adjustment and quality of life during a 1-year follow-up. METHODS: The
      sample was composed by 90 subjects (Group 1, D) clinically diagnosed with a major
      depressive episode and 41 patients (Group 2, Mx) for a sub-threshold mixed state.
      All patients were administered with a pharmacological treatment and evaluated for
      depressive, anxious and manic symptoms by common rating scales. Further
      evaluations included a global assessment of severity and functioning, social
      adjustment and quality of life. All evaluations were performed at baseline and
      after 1, 3, 6 and 12 months of treatment. RESULTS: The two groups were no
      different for baseline as well as improvement in global severity and functioning.
      Though clearly different for symptoms severity, the amount of change of
      depressive and anxiety symptoms was also no different. Manic symptoms showed
      instead a trend to persist over time in group 2, whereas a slight increase of
      manic symptoms was observed in group 1, especially after 6 months of treatment.
      Moreover, in group 1, some manic symptoms were also detected at the Young Mania
      Rating Scale (n = 24, 26.6%). Finally, improvement in quality of life and social
      adjustment was similar in the two groups, though a small trend toward a faster
      improvement in social adjustment in group 1. CONCLUSIONS: Sub-threshold mixed
      states have a substantial impact on global functioning, social adjustment and
      subjective well-being, similarly to that of acute phases, or at least major
      depression. In particular, mixed features, even in their sub-threshold forms,
      tend to be persistent over time. Finally, manic symptoms may be still often
      underestimated in depressive episodes, even in patients for BD.

PMID- 21728784
TI  - The T allele of the interferon-gamma +874A/T polymorphism is associated with
      bipolar disorder.
AB  - BACKGROUND: Previous studies have shown that patients with bipolar disorder (BD)
      tend to have altered immune system function. Several studies have reported that
      changes in interferon-gamma (IFN-gamma) may play an important role in the
      development of BD. AIMS: To investigate the relationship between IFN-gamma and
      BD, 156 patients with BD and 175 control subjects were genotyped for the IFN
      gamma +874A/T single nucleotide polymorphism. RESULTS: We detected significant
      differences in the genotype distributions and allele frequencies of the IFN-gamma
      +874A/T single nucleotide polymorphism (rs2430561) between patients with BD and
      normal controls. The T allele was found to be significantly more common among
      patients with BD than in controls. Additionally, significant differences in
      scores on the Young Mania Rating Scale (YMRS) were found between the three
      genotypes of this polymorphism. CONCLUSIONS: Our results suggest that the IFN
      gamma +874A/T polymorphism may have important effects related to susceptibility
      to BD and that the T allele may be associated with an increased risk of
      developing BD.

PMID- 21728785
TI  - Identification card and codification of the chemical and morphological
      characteristics of 14 dental implant surfaces.
AB  - Dental implants are commonly used in daily practice; however, most surgeons do
      not really know the characteristics of these biomedical devices they are placing
      in their patients. The objective of this work is to describe the chemical and
      morphological characteristics of 14 implant surfaces available on the market and
      to establish a simple and clear identification (ID) card for all of them,
      following the classification procedure developed in the Dohan Ehrenfest et al
      (2010) Codification (DEC) system. Fourteen implant surfaces were characterized:
      TiUnite (Nobel Biocare), Ospol (Ospol), Kohno HRPS (Sweden & Martina), Osseospeed
      (AstraTech), Ankylos (Dentsply Friadent), MTX (Zimmer), Promote (Camlog), BTI
      Interna (Biotechnology Institute), EVL Plus (SERF), Twinkon Ref (Tekka), Ossean
      (Intra-Lock), NanoTite (Biomet 3I), SLActive (ITI Straumann), Integra-CP/NanoTite
      (Bicon). Three samples of each implant were analyzed. Superficial chemical
      composition was analyzed using X-ray photoelectron spectroscopy/electron
      spectroscopy for chemical analysis, and the 100 nm in-depth profile was
      established using Auger electron spectroscopy. The microtopography was quantified
      using light interferometry. The general morphology and nanotopography were
      evaluated using a field emission-scanning electron microscope. Finally, the
      characterization code of each surface was established using the DEC system, and
      the main characteristics of each surface were summarized in a reader-friendly ID
      card. From a chemical standpoint, of the 14 different surfaces, 10 were based on
      a commercially pure titanium (grade 2 or 4), 3 on a titanium-aluminum alloy
      (grade 5 titanium), and one on a calcium phosphate core. Nine surfaces presented
      different forms of chemical impregnation or discontinuous coating of the titanium
      core, and 3 surfaces were covered with residual aluminablasting particles. Twelve
      surfaces presented different degrees of inorganic pollutions, and 2 presented a
      severe organic pollution overcoat. Only 2 surfaces presented no pollution
      (Osseospeed and Ossean). From a morphological standpoint, 2 surfaces were
      microporous (anodization) and 12 were microrough, with different
      microtopographical aspects and values. Ten surfaces were smooth on the nanoscale,
      and therefore presented no significant and repetitive nanostructures. Four
      implants were nanomodified: 2 implants were nanorough (Osseospeed and Ossean),
      and 2 were covered with nanoparticles (NanoTite and SLActive). TiUnite and Kohno
      HRPS were covered with extended cracks all over the surface. Only 8 surfaces
      could be considered homogeneous. This systematic approach allowed the main
      characteristics of these commercially available products to be gathered in a
      single ID card. It can be used as an experimental tool or a method for
      controlling industrial implant productions. The DEC system could be an
      interesting basis for the development of a clear and simple ISO standard for
      dental implant surfaces and other implantable devices.

PMID- 21728786
TI  - Potential for transcranial laser or LED therapy to treat stroke, traumatic brain
      injury, and neurodegenerative disease.

PMID- 21728788
TI  - Extra-amniotic balloon for preinduction cervical ripening: a randomized
      comparison of weighted traction versus unweighted.
AB  - OBJECTIVE: To determine whether a weighted versus unweighted balloon catheter
      achieved a shorter first stage of labor. METHODS: This was a randomized trial of
      patients undergoing induction with Bishop score <4. Women were randomized to
      weighted balloon catheter with 1000 mL fluid bag or unweighted catheter taped to
      the thigh. RESULTS: A total of 60 women were randomized. The time from balloon
      catheter insertion until discontinuation was significantly longer in the
      unweighted group 4.62 +/- 0.65 h versus 1.59 +/- 0.2 h in the weighted group (p =
      0.001). This resulted in longer cervical ripening/first stage of labor in the
      unweighted (18.52 +/- 0.96 h) versus weighted group (15.3 +/- 0.99 h) (p =
      0.025). The unweighted balloon catheter had a shorter first stage of labor as
      gravidity increased (p = 0.007) and as race went from white to non-white (p =
      0.003). There was no difference in perceived pain after balloon insertion (p =
      0.0942), or Bishop score after balloon discontinuation (p = 0.1661). CONCLUSION:
      The total time from cervical ripening to the end of the first stage of labor is
      significantly shortened with the weighted balloon catheter.

PMID- 21728789
TI  - Closure of persistent foramen ovale with the BioSTAR biodegradable PFO closure
      device: feasibility and long-term outcome.
AB  - OBJECTIVES: The presence of a patent foramen ovale (PFO) has been associated with
      recurrent cryptogenic cerebrovascular event (CVE). The BioSTAR is a partly
      biodegradeable atrial septal repair implant. We investigated the feasibility and
      efficacy of the BioSTAR PFO-occluder. DESIGN: From October 2007 to December 2008,
      59 consecutive patients underwent PFO closure at our institution with a history
      of at least one cryptogenic CVE defined by a neurologist. During the study
      period, all patients, who fulfilled our institutional criteria for PFO closure,
      were included. No patients were lost to follow-up. RESULTS: Of the 59 patients
      treated, a BioSTAR device could be implanted in 30 and in 29 patients another
      device, almost exclusively an Amplatzer, had to be used. No serious complications
      were observed during implantation of either. Four of 30 patients suffered a
      recurrent CVE after BioSTAR implantation as compared to 2/29 in the comparison
      group. At long-term follow-up 29/30 patients in the BioSTAR group had complete
      closure of their PFO as compared to 23 of 29 in the comparison group.
      CONCLUSIONS: The BioSTAR device could be selected for use in small shunts less
      than 10 mm while the Amplatzer may be chosen for larger defects or more
      complicated anatomy.

PMID- 21728790
TI  - Combining both generic and disease-specific properties: development of the McGill
      COPD quality of life questionnaire.
AB  - Presently, a generic and a disease-specific questionnaire are often co
      administered to capture the different domains of quality of life in chronic
      obstructive pulmonary disease (COPD) subjects. A health-related-quality of life
      (HRQL) questionnaire in COPD combining both generic and disease-specific
      properties is needed. OBJECTIVE: To develop a new, hybrid-HRQL questionnaire, the
      McGill-COPD-questionnaire, with qualities of both generic and disease-specific
      instruments. Using pre-defined criteria, we selected items from the SF-36 to
      complement the items from a COPD-specific-module to create the new hybrid-HRQL
      questionnaire. Domains were identified via confirmatory factor analysis. The
      McGill COPD questionnaire is available in English and French; it assesses three
      domains: symptoms, physical-function and feelings, has 29 items: 17 from the COPD
      specific-module and 12 from the SF-36. The symptom sub-scale has 6 items, all
      from the COPD-specific-module; the feelings sub-scale has 10 items, 5 each from
      COPD-specific-module and SF-36 and the physical-function sub-scale has 13 items,
      6 from COPD-specific-module and 7 from SF-36. The McGill COPD questionnaire was
      developed using a novel method of combining items from the SF-36 and a COPD
      specific-module. Thus, this new questionnaire has items from a generic
      questionnaire and a disease-specific-module and, hence, is promising to be a
      stand alone quality-of-life questionnaire for COPD subjects.

PMID- 21728791
TI  - Searching for digenic inheritance in deaf Brazilian individuals using the
      multiplex ligation-dependent probe amplification technique.
AB  - Mutations in the genes coding for connexin 26 (Cx26), connexin 30 (Cx30), and
      connexin 31 (Cx31) are the main cause of autosomal recessive nonsyndromic
      sensorineural hearing loss (AR-NSNHL). The 35delG mutation is the most frequent
      in the majority of Caucasian populations and may account for up to 70% of all
      GJB2 mutations. As a large number of affected individuals (10%-40%) with GJB2
      mutations carry only one mutant allele, it has been postulated that the presence
      of additional mutations in the GJB6 gene (Cx30) explains the deafness condition
      found in these patients. In the present study, we screened the c.35delG mutation
      in ~600 unrelated Brazilian patients, with moderate to profound AR-NSNHL. Other
      point mutations in the coding region of the GJB2 gene were screened by sequencing
      analysis as well as the IVS 1+1 G>A splice site mutation in the same gene.
      Digenic mutations including large deletions and duplications were investigated in
      the Cx26, 30, and 31 genes in monoallelic individuals for mutations in the GJB2
      gene. Large deletions and duplications were assessed by multiplex ligation
      dependent probe amplification. We found 46 patients with mutations in only one
      GJB2 allele. Different pathogenic mutations associated with c.35delG were found
      in 13 patients. Two patients were identified with digenic heterozygous mutations.
      Our findings contributed to more accurate diagnosis and more appropriate genetic
      counseling in 28% of patients studied (13/46).

PMID- 21728792
TI  - CYP2D6 genotyping in natives and immigrants from the Emilia-Romagna Region
      (Italy).
AB  - Pharmacogenetic testing of drug metabolizing enzyme polymorphisms provides an
      important tool to improve prescribing decisions, avoiding therapeutic failure and
      adverse drug reactions. Cytochrome P450 2D6 isoform plays an important role in
      the metabolism of about 20%-25% of widely used clinical drugs. Interethnic
      differences in allele frequency distribution of the CYP2D6 gene are well
      established, but interethnic admixture, introducing variations in population
      ancestry and resulting in distinct levels of population structure, should be
      acknowledged in pharmacogenomic studies to avoid inappropriate extrapolation of
      CYP2D6 data. The aim of the present research was to characterize CYP2D6
      polymorphism in a random sample of 122 natives and 175 immigrants from Africa,
      Asia, and South America living in the Emilia-Romagna region (Italy), considering
      the present scenario of immigration and back migration events, which is a source
      of admixture. The results are today consistent with the known interethnic genetic
      variation, but the observed significant divergence between natives and Africans
      or South-East Asians predicts that admixture will reshape the population
      structure and the native metabolic ratio curve requiring, for drug prescription
      and pharmacogenetics studies, an interdisciplinary approach applied in an
      appropriate biogeographical and anthropological frame.

PMID- 21728793
TI  - Glutathione S-transferase M1 and T1 gene polymorphisms and risk of hypertension
      in tea garden workers of North-East India.
AB  - AIMS: Polymorphisms of genes encoding phase II metabolic enzymes, for example,
      glutathione S-transferase, have been linked with hypertension. The present study
      aimed at finding out the association between GSTM1 and GSTT1 polymorphism and
      hypertension in a population from North-East India. MATERIALS AND METHODS: We
      carried out a case-control study in tea garden workers of Assam. A total of 223
      hypertensive cases and 236 normotensive control subjects were recruited with a
      record of socio-demographic information, blood pressure, and anthropometric data.
      Fasting venous blood samples from all subjects were obtained and subjected to DNA
      extraction and polymerase chain reaction to detect polymorphism of the GSTM1 and
      GSTT1 genes. RESULTS: The null genotype was prevalent in 38.1% and 28.1% of the
      study participants (cases and controls) for GSTM1 and GSTT1 genes, respectively.
      Hypertensive subjects had a significantly higher prevalence of the GSTM1 null
      genotype (43% vs. 33.5%, than normotensive control subjects, p=0.035).
      Association between the GSTM1 null genotype and hypertension was significant in
      younger subjects. Tobacco users with the GSTT1 null genotype were at an increased
      risk for hypertension. CONCLUSION: The knowledge of GSTM1 and GSTT1 variant
      status will be useful to predict the risk of hypertension in a population.

PMID- 21728794
TI  - Copulatory courtship behavior and sine song as a mate recognition cue in
      Drosophila lini and its sibling species.
AB  - Most Drosophila species sing species-specific pulse songs during their
      "precopulatory courtship." Three sibling species of the Drosophila montium
      species subgroup performed "copulatory courtship": males generated courtship
      songs by vibrating either wing only after mounting and during copulation. In
      these three species, strong sexual isolation was detected between D. ohnishii and
      D. lini and between D. ohnishii and D. ogumai, but not between D. lini and D.
      ogumai. Female showed strong repelling behavior when they were mounted by a
      heterospecific male in the species combinations including D. ohnishii, resulting
      in failure of the copulation attempt of the male. Acoustic analyses of courtship
      songs revealed that the pulse song was irregular, without any species-specific
      parameters, but that the frequency of the sine song was different among the three
      species in accordance with the modes of sexual isolation between them; it was
      significantly lower in D. ohnishii (mean +/- SE = 193.0 +/- 1.7 Hz) but higher in
      D. lini (253.4 +/- 2.7 Hz) and D. ogumai (246.7 +/- 5.3 Hz). We suggest that this
      difference in the sine song frequency is a sexual signal in the Specific Mate
      Recognition System (SMRS) among these three Drosophila species.

PMID- 21728795
TI  - Influences of the interference of gamma-tubulin gene expression on the morphology
      and microtubules of ciliate Euplotes eurystomus.
AB  - A recombinant plasmid L4440-GTU expressing gamma-tubulin dsRNA of the ciliate
      Euplotes eurystomus was constructed and transferred into Escherichia coli strain
      HT115. The resultant E. coli bacteria were fed on E. eurystomus to inhibit the
      ciliate's gamma-tubulin gene expression. As a result, the gamma-tubulin gene
      expression level was decreased, and this inactivation blocked cell division,
      which was lethal. In addition, the loss of the C-tubule from the nine-microtubule
      triplets in basal bodies, and the disappearance of some microtubules or
      mislocalization of some microtubule organization units in the subpellicular
      microtubule layers were also observed. These results indicate that the gamma
      tubulin is not only important for the stability of the nine-microtubule triplets
      in basal bodies, but also necessary for the integrity of microtubule organization
      patterns in the subpellicular microtubule layer.

PMID- 21728796
TI  - Amitotic division of the macronucleus in Tetrahymena thermophila: DNA
      distribution by genomic unit.
AB  - The macronucleus of the ciliate Tetrahymena cell contains euchromatin and
      numerous heterochromatins called chromatin bodies. During cell division, a
      chromatin aggregate larger than chromatin body appears in the macronucleus. We
      observed chromatin aggregates in the dividing macronucleus in a living T.
      thermophila cell, and found that these were globular in morphology and
      homogeneous in size. To observe globular chromatin clearly, optimal conditions
      for making it compact were studied. Addition of Mg ion, benomyl and oryzalin,
      microtubule inhibitors, to cell suspension was effective. Globular chromatin
      appeared when the micronuclear anaphase began at the cell cortex, and disappeared
      long after cell separation. Using living cells with a small macronucleus at early
      log phase, we counted the number of globular chromatin per nucleus and measured
      the DNA content of globular chromatin in the macronucleus which was stained with
      Hoechst 33342 by using ImageJ. The number of globular chromatin per nucleus was
      reduced by half after division, indicating the globular chromatin is a
      distribution unit of DNA. A globular chromatin contained similar DNA content as
      that of the macronuclear genome. We developed methods for inducing and isolating
      a cell with an extremely small macronucleus with a DNA amount of one globular
      chromatin. These cells grew, divided, and give clones, suggesting that the
      macronuclear genome is not dispersed within the macronucleus and the globular
      chromatin may be a macronuclear genome. We named this globular chromatin
      "macronuclear genome unit" (MGU).

PMID- 21728797
TI  - Timing of ossification in duck, quail, and zebra finch: intraspecific variation,
      heterochronies, and life history evolution.
AB  - Skeletogenic heterochronies have gained much attention in comparative
      developmental biology. The temporal appearance of mineralized individual bones in
      a species - the species ossification sequence - is an excellent marker in this
      kind of study. Several publications describe interspecific variation, but only
      very few detail intraspecific variation. In this study, we describe and analyze
      the temporal order of ossification of skeletal elements in the zebra finch,
      Taeniopygia guttata, the Japanese quail, Coturnix coturnix japonica, and the
      White Pekin duck, a domestic race of the mallard Anas platyrhynchos, and explore
      patterns of intraspecific variation in these events. The overall sequences were
      found to be conserved. In the duck, variability is present in the relative timing
      of ossification in the occipital, the basisphenoid and the otic regions of the
      skull and the phalanges in the postcranium. This variation appears generally in
      close temporal proximity. Comparison with previously published data shows
      differences in ossification sequence in the skull, the feet, and the pelvis in
      the duck, and especially the pelvis in the quail. This clearly documents
      variability among different breeds.

PMID- 21728798
TI  - Wolbachia infections in world populations of bean beetles (Coleoptera:
      Chrysomelidae: Bruchinae) infesting cultivated and wild legumes.
AB  - Wolbachia endosymbionts are widespread among insects and other arthropods, often
      causing cytoplasmic incompatibility and other reproductive phenotypes in their
      hosts. Recently, possibilities of Wolbachia-mediated pest control and management
      have been proposed, and the bean beetles of the subfamily Bruchinae are known as
      serious pests of harvested and stored beans worldwide. Here we investigated
      Wolbachia infections in bean beetles from the world, representing seven genera,
      20 species and 87 populations. Of 20 species examined, Wolbachia infections were
      detected in four species, Megabruchidius sophorae, Callosobruchus analis, C.
      latealbus and C. chinensis. Infection frequencies were partial in M. sophorae but
      perfect in the other species. In addition to C. chinensis described in the
      previous studies, C. latealbus was infected with two distinct Wolbachia strains.
      These Wolbachia strains from the bean beetles were phylogenetically not closely
      related to each other. Among world populations of C. chinensis, some Taiwanese
      populations on a wild leguminous plant, Rhynchosia minima, exhibited a peculiar
      Wolbachia infection pattern, suggesting the possibility that these populations
      comprise a distinct host race or a cryptic species.

PMID- 21728799
TI  - Chronic transplantation immunity in newts: temperature susceptibility of an
      effector phase in allo-skin graft rejection.
AB  - Urodele amphibians are unique due to their greatly reduced immune responsiveness
      compared to bony fishes, which show acute immune responsiveness. In newts, the
      mean survival time of allogenic skin grafts in the transplantation immunity was
      48.8 +/- 8.3 days at 25 degrees C, suggesting that it occurs in a chronic manner.
      The graft rejection process was categorized into three stages: a latent stage
      with frequent blood circulation, or the immune induction phase; a vascular
      stoppage stage with dominant infiltrating cells of T cells; and a rejection stage
      showing the change of the dominant cells to monocytes/macrophages, probably as
      effector cells, tetntatively referred to as the immune effector phase. The immune
      induction phase is susceptible to the cyclophosphamide (CY) mitosis inhibitor,
      but not to a temperature shift from 18 to 27 degrees C, while the immune effector
      phase is susceptible to temperature shifts, but not CY-treatment, although the
      temperature shift failed to shorten the graft survival time to less than 25 days,
      which nearly equals that of the secondary set of grafts where the lack of
      complete blood circulation is remarkable and graft rejection is resistant to CY
      treatment. In contrast, a very low temperature (5-10 degrees C) completely
      prevented effector generation in newts; in frogs, however, it is reported that
      such low temperatures did not prevent the generation of effectors. Taken
      together, these data suggest that chronic responses in newts are due to effector
      cells other than cytotoxic T cells; possible effector cells are discussed.

PMID- 21728800
TI  - Multiple subtypes of serotonin receptors in the feeding circuit of a pond snail.
AB  - In the central nervous system of the pond snail Lymnaea stagnalis, serotonergic
      transmission plays an important role in controlling feeding behavior. Recent
      electrophysiological studies have claimed that only metabotropic serotonin (5
      HT(2)) receptors, and not ionotropic (5-HT(3)) receptors, are used in synapses
      between serotonergic neurons (the cerebral giant cells, CGCs) and the follower
      buccal motoneurons (the B1 cells). However, these data are inconsistent with
      previous results. In the present study, we therefore reexamined the serotonin
      receptors to identify the receptor subtypes functioning in the synapses between
      the CGCs and the B1 cells by recording the compound excitatory postsynaptic
      potential (EPSP) of the B1 cells evoked by a train of stimulation to the CGC in
      the presence of antagonists: cinanserin for 5-HT(2) and/or MDL72222 for 5-HT(3).
      The compound EPSP amplitude was partially suppressed by the application of these
      antagonists. The rise time of the compound EPSP was longer in the presence of
      MDL72222 than in that of cinanserin. These results suggest that these two
      subtypes of serotonin receptors are involved in the CGC-B1 synapses, and that
      these receptors contribute to compound EPSP. That is, the fast component of
      compound EPSP is mediated by 5-HT(3)-like receptors, and the slow component is
      generated via 5-HT(2)-like receptors.

PMID- 21728801
TI  - Origin and possible role of males in hermaphroditic androgenetic Corbicula clams.
AB  - Hermaphroditic Corbicula leana clams reproduce by androgenesis and have been
      regarded as simultaneous hermaphrodites. To date, there has been no report on the
      occurrence of male clams in hermaphroditic Corbicula. In an irrigation ditch in
      Shiga Prefecture, we found that 78.2% of C. leana specimens were males and 21.8%
      were hermaphrodites. Microfluorometric analysis revealed that males were diploids
      and hermaphrodites were triploids. All males produced nonreductional and
      biflagellate spermatozoa. The sequence analysis of mitochondrial DNA (cytochrome
      b, 621 bp) for 31 specimens of C. leana showed that four male and nine
      hermaphrodites shared the same H2 mtDNA haplotype; H1 was detected from 17 males
      and H3 was detected from one hermaphrodite. Coexisting C. fluminea clams also
      have haplotypes H1 and H2. Phylogenetic tree by a neighborjoining method based on
      the partial sequence of cytochrome b revealed that the haplotypes (H1- 3) of C.
      leana were evidently different from those of dioecious C. sandai (S1 and S2) and
      C. japonica (J1 and J2). These results suggest that males may be derived from
      hermaphrodite C. leana clams. The role of males in hermaphroditic populations is
      unknown. However, if the spermatozoon from a male is able to fertilize an egg
      from a hermaphrodite and the nuclear genome of the egg is expelled as polar
      bodies, the sperm nucleus could form a zygote nucleus. This mode of reproduction
      would allow the replacement of the nuclear genome.

PMID- 21728802
TI  - Studies on Japanese botryllid ascidians. V. A new species of the genus
      Botrylloides very similar to Botrylloides simodensis in morphology.
AB  - Botrylloides simodensis, belonging to the family Botryllidae, is a common species
      on the rocky shore around Shimoda. Since this species was first reported in 1981,
      it has been noticed that some B. simodensis colonies have distinctly different
      ground colors and color patterns from colonies including type specimens (holotype
      and all of paratypes) of B. simodensis. However, as there is no remarkable
      difference among them in morphology other than the colonial colors and color
      patterns, they have been considered to belong to the same species. In the present
      work, colonies of B. simodensis sensu lato were divided into three groups, two
      major and one minor, based on their color-morphs and periods of sexual
      reproduction. In one of the major groups, B. simodensis sensu strict, the period
      of sexual reproduction was limited from July to September, as shown in the
      original description. The other major group engaged in sexual reproduction for
      much longer than the former group, and they frequently made clusters of vascular
      vessels and underwent vascular budding. Therefore, the group with the long period
      of sexual reproduction was described as a new species of the genus Botrylloides
      here. In addition, phylogenetic analysis based on mtDNA sequences of these groups
      indicated that each group had a peculiar sequence, and that they were genetically
      separated.

PMID- 21728804
TI  - Daily physical activity in patients with chronic obstructive pulmonary disease: a
      systematic review.
AB  - Patients with chronic obstructive pulmonary disease (COPD) are often limited in
      their daily physical activity. However, the level, type and intensity of daily
      physical activity are not known, nor there is a clear insight in the contributing
      factors. The aim of this review is to describe daily physical activity of COPD
      patients, and to examine its relationship with demographic factors, pulmonary
      function, physical fitness, systemic inflammation and quality of life. A
      systematic literature search was conducted, including studies assessing daily
      physical activity in all stages of COPD by various different types of measurement
      techniques. In total, 47 studies were selected; 17 performance-, 20 questionnaire
      , and 12 interview-based. Two studies used both a performance- and questionnaire
      based method. Overall, COPD patients have a lower level and intensity of daily
      physical activity compared to healthy controls. This was reported by performance-
      as well as questionnaire-based studies, yet with a large variation (42-86% and 28
      97%, respectively). Reduced daily physical activity is associated with higher
      levels of airway obstruction, higher levels of systemic inflammation, and lower
      levels of physical fitness. The association between daily physical activity and
      quality of life is less clear. In conclusion, this is the first review that
      examined the level, type and determinants of daily physical activity in COPD. It
      demonstrates that reduced daily physical activity frequently occurs in COPD
      patients, yet with a large variation. Methods of measuring and reporting daily
      physical activity should be more standardized.

PMID- 21728805
TI  - Eccentric cycle exercise in severe COPD: feasibility of application.
AB  - Eccentric cycling may present an interesting alternative to traditional exercise
      rehabilitation for patients with advanced COPD, because of the low ventilatory
      cost associated with lengthening muscle actions. However, due to muscle damage
      and soreness typically associated with eccentric exercise, there has been
      reluctance in using this modality in clinical populations. This study assessed
      the feasibility of applying an eccentric cycling protocol, based on progressive
      muscle overload, in six severe COPD patients with the aim of minimizing side
      effects and maximizing compliance. Over 5 weeks, eccentric cycling power was
      progressively increased in all patients from a minimal 10-Watt workload to a
      target intensity of 60% peak oxygen consumption (attained in a concentric
      modality). By 5 weeks, patients were able to cycle on average at a 7-fold higher
      power output relative to baseline, with heart rate being maintained at ~85% of
      peak. All patients complied with the protocol and presented tolerable dyspnea and
      leg fatigue throughout the study; muscle soreness was minimal and did not
      compromise increases in power; creatine kinase remained within normal range or
      was slightly elevated; and most patients showed a breathing reserve > 15 L.min(
      1). At the target intensity, ventilation and breathing frequency during eccentric
      cycling were similar to concentric cycling while power was approximately five
      times higher (p = 0.02). This study showed that an eccentric cycling protocol
      based on progressive increases in workload is feasible in severe COPD, with no
      side effects and high compliance, thus warranting further study into its efficacy
      as a training intervention.

PMID- 21728806
TI  - The COPD Pipeline XI.

PMID- 21728808
TI  - Proteasome modulator 9 gene is linked to diabetic and non-diabetic retinopathy in
      T2D.
AB  - BACKGROUND: Diabetic retinopathy is a long-term complication of type 2 diabetes
      (T2D). Non-diabetic retinopathy may be present in T2D patients as well and non
      T2D patients with hypertension and/or atherosclerosis. The aim of this study was
      to identify linkage of the proteasome modulator 9 (PSMD9) T2D risk variants
      IVS3+nt460, IVS3+nt437, E197G to diabetic retinopathy and retinopathy including
      also atherosclerotic or hypertensive retinopathy in Italian T2D families.
      MATERIALS AND METHODS: A total of 126 siblings of our 200 T2D siblings/families
      were characterized for diabetic retinopathy or retinopathy. The clinical
      characterization is based on a fundus oculi exam and on fluorangiography of the
      participating subjects. Diabetic retinopathy includes both pre-proliferative and
      proliferative retinopathy. The common gene variants were directly amplified by
      PCR and by fluorescent-based automation. A parametric and non-parametric linkage
      study of the gene variants with diabetic retinopathy and retinopathy was then
      performed using Merlin software. Finally, 1000 simulation analyses were performed
      to test for the statistical power of the significant results (P-value <= 0.05).
      RESULTS: This study shows a linkage of the PSMD9 IVS3+nt460 (rs74421874),
      IVS3+nt437 (rs3825172) and E197G (rs14259) single nucleotide polymorphisms (SNPs)
      to diabetic and non-diabetic retinopathy by using the non-parametric as well as
      the parametric linkage analysis. The strongest signal is present for the PSMD9
      variants with the diabetic retinopathy, in particular under the additive model.
      The 1,000 simulations performed for each significant test confirmed that the
      results are not due to random chance. CONCLUSIONS: In summary, the PSMD9
      IVS3+nt460, IVS3+nt437, E197G SNPs are linked to diabetic retinopathy and non
      diabetic retinopathy in Italians.

PMID- 21728809
TI  - Strabismus, refractive errors and nystagmus in children and young adults with
      Down syndrome.
AB  - PURPOSE: The aims of the present population-based, cross-sectional study were to
      examine the frequency and type of strabismus, refractive errors and nystagmus in
      children and young adults with Down syndrome (DS) in Macedonia and Croatia.
      METHODS: A total of 170 unselected children and young adults with DS aged 1-34
      years were examined for ocular findings. The ocular examination included: a
      visual acuity assessment, cycloplegic refraction, ocular alignment and ocular
      motility. RESULTS: Strabismus was found in 45 of 170 children (26.5%), and
      esodeviation was the most common type. Nine (20%) had exodeviation and 4 (8.9%)
      vertical deviation. In 27 of 32 esotropic patients, the strabismus was regarded
      as acquired esodeviations. The frequency of strabismus was lowest in the high
      grade hyperopia group (5%). Concerning esodeviations, fewer cases (3%) were in
      the high-grade hyperopia group. Most of the cases with esodeviations were in
      correlation with low-grade hyperopia (31%), myopia (28 %) and emetropia (16%).
      Hyperopia was the most common refractive error and high myopia increased in
      prevalence in the over 20 age group. Astigmatism was present in 72.4% of
      patients. Nystagmus was observed in 18 patients. Ten of 18 patients with
      nystagmus were associated with the presence of strabismus (9 esodeviations, 1
      exotropia). CONCLUSION: In our study, the high prevalence of strabismus can not
      be attributed to the presence of hyperopia. Our data show no association between
      refraction and strabismus in children with DS. Oblique astigmatism has been found
      to be the most common type of astigmatism in our study group.

PMID- 21728810
TI  - A novel TFAP2A mutation in familial Branchio-Oculo-Facial Syndrome with
      predominant ocular phenotype.
AB  - INTRODUCTION: Branchio-Oculo-Facial Syndrome (BOFS) is a rare autosomal dominant
      congenital disorder defined by branchial defects, ocular anomalies and
      craniofacial malformations, including variable degrees of cleft lip with or
      without cleft palate. In addition, temporal bone anomalies, renal and ectodermal
      manifestations can be present. Mutations in the TFAP2A gene have been reported in
      patients with BOFS, prompting phenotype-genotype studies because of the variable
      clinical spectrum. MATERIALS AND METHODS: We report on a family (a mother, her
      daughter and son) with BOFS and significant variability in clinical expression.
      The daughter presents predominantly with an ocular phenotype of unilateral
      microphthalmia and bilateral chorioretinal colobomas, whereas her brother is more
      severely affected contrasting with the paucisymptomatic mother. TFAP2A molecular
      analysis revealed a novel frameshift mutation. DISCUSSION: We confirm the wide
      clinical spectrum of BOFS. The importance of upper lip examination in mild and
      paucisymptomatic cases is underlined. TFAP2A mutation spectrum is discussed and
      broadened by the report of the second frameshift mutation in this gene.
      CONCLUSION: Patients with BOFS and predominant ocular phenotypes can be
      underdiagnosed. In such cases, upper lip examination can be of important
      diagnostic value. TFAP2A analysis provides diagnostic confirmation and improves
      genetic counselling.

PMID- 21728811
TI  - Cone-rod dystrophy associated with amelogenesis imperfecta in a child with
      neurofibromatosis type 1.
AB  - PURPOSE: To report a case of a 9-year-old child with neurofibromatosis type 1
      (NF1) and Jalili syndrome, the latter denoting a rare combination of cone-rod
      dystrophy and amelogenesis imperfecta. METHODS: Detailed ophthalmological and
      electrophysiological examinations were carried out and blood samples were taken
      from the patient and her father for molecular genetic analysis by direct DNA
      sequencing of the NF1 and the ancient conserved domain protein 4 (CNNM4) gene.
      RESULTS: The diagnosis of neurofibromatosis type 1 (NF1) could be confirmed
      clinically and genetically. Furthermore, cone-rod dystrophy and amelogenesis
      imperfecta could be observed as typical features of a rare condition,
      acknowledged as Jalili syndrome. The diagnosis was assured on the basis of
      clinical examinations and molecular genetic analysis of the CNNM4 gene, which was
      previously shown to cause Jalili syndrome. CONCLUSION: Our case shows a unique
      combination of NF1 and Jalili syndrome. The random association of two diseases is
      unusual and deserves attention. This case highlights the importance not only of
      detailed clinical examination, but also of molecular genetic analysis, which
      together provide a precise diagnosis.

PMID- 21728812
TI  - Development of competitive immunoassays to hydroxyl containing fungicide
      metabolites.
AB  - This paper describes the isolation of monoclonal antibodies and the development
      of competitive immunoassays to pesticide metabolites of the fungicides imazalil,
      carbendazim and thiabendazole. The metabolite specific hydroxyl residues were
      used as the reactive group with which to link the metabolite to the carrier
      proteins Keyhole Limpet Haemocyanin (KLH) and Bovine Serum Albumin (BSA). In each
      case immune responses in mice were raised and monoclonal antibodies were
      produced. Antibodies were developed into competitive ELISAs to the appropriate
      metabolite. The antibody raised to a metabolite of imazalil was optimised into a
      competitive ELISA format which had an assay IC50 of 7.5 MUg/L and a limit of
      detection (LOD) of 1.1 MUg/L. A single antibody isolated against the metabolite
      of carbendazim had assay IC50s of 3.2 and 2.7 MUg/L for the metabolites of
      carbendazim and thiabendazole respectively with an LOD of 0.38 MUg/L for both.
      These sensitive immunoassays may have application in the monitoring of human
      exposure to these fungicide residues either by occupational or non-occupational
      routes.

PMID- 21728813
TI  - Incidental findings in data-intensive postgenomics science and legal liability of
      clinician-researchers: ready for vaccinomics?
AB  - Vaccinomics encompasses a host of multiomics approaches to characterize
      variability in host-environment (including pathogens) interactions, with a view
      to a more directed or personalized use of vaccine-based health interventions.
      Although vaccinomics has the potential to reduce adverse effects and increase
      efficacy of vaccines, the use of high-throughput, data-intensive technologies may
      also lead to unanticipated discoveries beyond the initial aims of a vaccinomics
      study--discoveries that could be highly significant to the health of the research
      participants. How do clinician-researchers faced with such information have to
      act? What are the attendant legal duties in such circumstances and how do they
      differ from the duties of non-clinician researchers? Together with a critical
      analysis of the international laws and policies framing researchers' duties with
      regard to incidental findings, this article also draws from Quebec's civil law-
      with its rich jurisprudence on clinician and researcher liability--as a case
      study to evaluate the potential legal implications associated with vaccinomics
      investigations. Given previous lessons learned from other data-intensive
      sciences, the education of clinician-researchers with regard to their roles,
      limitations, and legal obligations remains an important strategy to prevent
      potential legal complications and civil liability in vaccinomics research in the
      postgenomics era.

PMID- 21728814
TI  - Diagnostic testing for vaccinomics: is the regulatory approval framework
      adequate? A comparison of Canada, the United States, and Europe.
AB  - Vaccinomics aims to integrate variability information from multiple levels of the
      biological hierarchy from genome to proteome to metabolome, and ways in which
      these biological parts interact with each other and the environment. Vaccinomics
      holds significant promise as a new public health tool in designing safer and more
      effective vaccines for both developed and developing countries. Vaccinomics tests
      that are envisioned to be used in tandem with vaccine-based health interventions
      could permit an informed forecast of individual and subpopulation variations in
      immune responses to vaccines, reduce adverse effects, and contribute to a
      foundation for rational and directed use of vaccines. A proactive,
      multidisciplinary engagement with vaccinomics is now timely and much needed in
      order to develop regulations that best ensure the protection of the public and
      promote the transition of vaccinomics innovations from discovery to real-life
      public health applications. This article examines and compares the regulatory
      oversight of vaccinomics tests in Canada, the United States, and Europe. Recent
      trends in these jurisdictions suggest that regulatory agencies view personalized
      genomics/omics medicine, such as vaccinomics, as a desirable goal. At the same
      time, proposals to increase oversight could impact progress in the field and
      affect the availability of vaccinomics tests in public health practice and the
      diagnostic test market. The comparative analysis of vaccinomics in three
      jurisdictions presented in this article highlights both the convergence and
      divergence of regulatory oversight. In a rapidly emerging field such as
      vaccinomics that is pivotal for global public health, achieving better
      harmonization of policies may be an advantageous target, while ensuring that
      symmetry exists between the goals of public safety and promoting public health
      innovation. We suggest it is now timely to proactively initiate a constructive
      dialogue among all stakeholders (publics, policymakers, researchers, private
      sector, governments) to foster the development of appropriately targeted
      regulatory policies in this field.

PMID- 21728815
TI  - Mechanical phenotyping of mouse embryonic stem cells: increase in stiffness with
      differentiation.
AB  - Atomic force microscopy (AFM) has emerged as a promising tool to characterize the
      mechanical properties of biological materials and cells. In our studies,
      undifferentiated and early differentiating mouse embryonic stem cells (mESCs)
      were assessed individually using an AFM system to determine if we could detect
      changes in their mechanical properties by surface probing. Probes with pyramidal
      and spherical tips were assessed, as were different analytical models for
      evaluating the data. The combination of AFM probing with a spherical tip and
      analysis using the Hertz model provided the best fit to the experimental data
      obtained and thus provided the best approximation of the elastic modulus. Our
      results showed that after only 6 days of differentiation, individual cell
      stiffness increased significantly with early differentiating mESCs having an
      elastic modulus two- to threefold higher than undifferentiated mESCs, regardless
      of cell line (R1 or D3 mESCs) or treatment. Single-touch (indentation) probing of
      individual cells is minimally invasive compared to other techniques. Therefore,
      this method of mechanical phenotyping should prove to be a valuable tool in the
      development of improved methods of identification and targeted cellular
      differentiation of embryonic, adult, and induced-pluripotent stem cells for
      therapeutic and diagnostic purposes.

PMID- 21728816
TI  - The efficiency of cell fusion-based reprogramming is affected by the somatic cell
      type and the in vitro age of somatic cells.
AB  - Cell fusion is one approach that has been used to demonstrate nuclear
      reprogramming of somatic cells to a pluripotent-like state and is a useful tool
      for screening factors involved in reprogramming. Recent cell fusion studies
      reported that the overexpression of Nanog and SalI could improve the efficiency
      of reprogramming, whereas AID was shown to be essential for DNA demethylation and
      initiation of reprogramming. The aim of this study was to investigate factors
      affecting the reprogramming efficiency following cell fusion. We conducted
      fusions of mouse embryonic stem cells (ESCs) with somatic cells carrying a GFP
      transgene under control of the Oct4 promoter (Oct4-GFP), which is normally
      repressed in nonpluripotent cells. The effect of somatic cell type on the
      reprogramming efficiency was investigated using Oct4-GFP expression as an
      indicator. Different somatic cell types were tested including mesenchymal stem
      cells (MSCs), adipose tissue-derived cells (ADCs), neural stem cells (NSCs), and
      these were compared with the mouse embryonic fibroblast (mEF) standard. The
      reprogramming efficiencies differed greatly, with mEFs (0.477 +/- 0.003%) and
      MSCs (0.313 +/- 0.003%) showing highest efficiencies while NSCs (0.023 +/-
      0.014%), and ADCs (0.006 +/- 0.006%) had significantly lower reprogramming
      efficiencies (p < 0.05). The differences in the reprogramming efficiencies
      observed could be in part explained by the in vitro age of the somatic cells
      used. We demonstrated that the reprogramming efficiency of early passage mEFs was
      significantly higher compared with late passage mEFs (0.330 +/- 0.166% vs. 0.021
      +/- 0.011%, p < 0.05), suggesting that senescence can affect reprogramming
      potential. In summary, this study shows that different somatic cell types do not
      have equivalent potential to be reprogrammed following fusion with ESCs.
      Furthermore, the in vitro age of somatic cells can also affect the
      reprogrammability of somatic cells. These findings constitute an important
      consideration for reprogramming studies.

PMID- 21728817
TI  - Exploring the underlying structure of personal Web usage in the workplace.
AB  - Personal Web usage (PWU) represents a tension between employers and employees as
      employers generally regard employees' PWU as negative and employees see many PWU
      behaviors as acceptable. Employers attempt to limit PWU primarily through
      electronic monitoring and Internet usage policies. Employees, however, find PWU
      not only permissible, but also useful and rationalize these workplace behaviors.
      While researchers identified many PWU behaviors, the underlying structure of the
      phenomenon is not clearly understood. In this article, we offer a comprehensive
      new definition of PWU, and develop an empirically grounded classification of PWU
      framed by psychological contract theory and based on two studies. Using
      multidimensional scaling techniques and cluster analysis, we identified four
      clusters of PWU behaviors-work/family, hedonic, self-development, and
      citizenship. The results provide information as to what constitutes the domain of
      PWU, and how various usages are related to one another via the dimensions of
      individual and organizational benefits. We offer directions for future work and
      suggest how our work might be useful to practitioners.

PMID- 21728818
TI  - Orthodontic considerations in restorative management of hypodontia patients with
      endosseous implants.
AB  - The use of implant-supported restorations in patients with hypodontia remains
      challenging and requires a multistage treatment that begins in late mixed
      dentition and continues into late adolescence. The aim of this article is to
      review the role of orthodontics in endosseous implant rehabilitation of patients
      with hypodontia. The MEDLINE, Web of Science, Scopus, Cochrane databases, and
      necessary scientific textbooks were searched for relevant studies and reviews,
      and as far as possible, they were only included if they had been cited at least
      once in the literature. Dental implants are susceptible to overloading as the
      periodontal ligament is absent and the proprioceptive nerve endings are either
      lacking or very limited. Patients with hypodontia may present with skeletal
      features such as short and retrognathic maxilla, prognathic mandible, and shorter
      lower anterior facial height, and they sometimes need orthognathic correction as
      part of their overall treatment. Dental problems vary and include bimaxillary
      retroclination of incisors, spacing, centerline discrepancies, microdontia,
      hypoplastic enamels, ankylosis of the retained primary teeth, overeruptions, and
      volume deficiencies of alveolar ridges. The challenges mentioned, as well as bone
      volume deficiencies, compromise the successful placement of implants. Orthodontic
      strategies and techniques, such as uprighting mechanics, extrusion/intrusion,
      delayed space opening, and orthodontic implant site-switching, can be used to
      create, preserve, or augment the implant site. After orthodontic site
      development, the final planned position of the teeth should be maintained with a
      rigid bonded retainer; overlooking this stage may compromise the implant site and
      require orthodontic retreatment.

PMID- 21728819
TI  - Rapid detection of lily symptomless virus with CdTe quantum dots by flow
      cytometry.
AB  - Lily symptomless virus (LSV) is the most common lily virus, being detected in
      many species and hybrids. We established a microsphere-based fluorescent
      immunoassay for the determination of LSV, using a polyclonal antibody against LSV
      covalently bound to carboxy-modified microspheres able to capture LSV antigen. A
      monoclonal antibody against LSV conjugated to quantum dots (QDs) was used as a
      fluorescent probe, enabling LSV to be fluorescently detected by a combination of
      encoded beads and QDs. This method was 16 times more sensitive than ELISA in the
      detection of LSV, and could potentially be applied to the simultaneous detection
      of inhomogeneous matter.

PMID- 21728820
TI  - Influence of different length linker containing DHEA-7-CMO-enzyme conjugates on
      sensitivity and specificity of DHEA-17-CMO-antibody.
AB  - Introduction of spacers in enzyme conjugates is known to exert an influence on
      the assay parameters of steroid enzyme immunoassays. We have introduced 3 to 10
      atomic length linkers between enzyme and steroid moieties and studied their
      effects on sensitivity and specificity of dehydroepiandrosterone enzyme
      immunoassays. Dehydroepiandrosterone-17-carboxymethyloxime-bovine serum albumin
      (DHEA-17-CMO-BSA) was used as an immunogen to raise the antiserum in New Zealand
      white rabbits. Five enzyme conjugates were prepared using DHEA-7-CMO as
      carboxylic derivative of DHEA and horseradish peroxidase (HRP) as label. These
      were DHEA-7-CMO-HRP, DHEA-7-CMO-urea-HRP (DHEA-7-CMO-U-HRP), DHEA-7-CMO
      ehylenediamine-HRP (DHEA-7-CMO-EDA-HRP), DHEA-7-CMO-carbohydrazide-HRP (DHEA-7
      CMO-CH-HRP), and DHEA-7-CMO-adipic acid dihydrazide-HRP (DHEA-7-CMO-ADH-HRP). The
      influence of different atomic length linkers on sensitivity and specificity were
      studied with reference to label without linker. The results of the present
      investigation revealed that with incorporation of linkers, the sensitivity
      improves, whereas specificity only marginally improves. These differential
      behaviors of various linkers toward the sensitivity and specificity of assays
      might be due to the difference in the magnitude of overall forces of attraction
      between the antibody and the enzyme conjugates.

PMID- 21728821
TI  - Determination of defensin HNP-1 in human saliva of patients with oral mucosal
      diseases.
AB  - Saliva is a biological fluid that is easily obtainable and that can give useful
      information both in systemic and oral diseases. In this study, a chromatographic
      method was applied to determine the amount of defensin HNP-1 in human saliva of
      patients with oral mucosal diseases before and after treatments and compared with
      controls. Defensin human neutrophil peptide-1 (HNP-1) was identified and
      confirmed. The concentration of HNP-1 in saliva was determined by comparing the
      area of eluted HNP-1 with that of HNP-1 standard. Linear calibration range of
      defensin HNP-1 was 0.10 to 0.90 MUg/10 MUL with R(2) values of 0.996. The
      concentrations of HNP-1 in the saliva of patients with oral lichen planus,
      Behcet's disease, and recurrent apthous stomatitis were 33.6 +/- 10.6, 15.5 +/-
      7.6, and 36.3 +/- 9.5 MUg mL(-1) (mean +/- S.D.), respectively. The salivary
      defensin-1 concentration was significantly higher in patients with oral mucosal
      diseases than in healthy volunteers; furthermore, in patients with oral mucosal
      diseases, the concentration was significantly higher before treatment than after
      treatment.

PMID- 21728822
TI  - Validation of preclinical pharmacokinetic and immunogenicity assays for an anti
      PCSK9 antibody.
AB  - Pharmacokinetic data derived from assays that accurately and precisely quantitate
      a therapeutic drug in circulation are critical to appropriately designing
      suitable dosing schedules. This manuscript describes the validation and
      implementation of methods to quantitate a therapeutic anti-human PCSK9 monoclonal
      antibody in rat and monkey sera as well as immunogenicity methods to screen the
      possible presence of rat and monkey antibodies directed against the antibody. As
      soluble, endogenous PCSK9 can interfere with a PCSK9-mediated capture step in
      ELISA, an indirect target-capture assay was used that potentially could capture
      free and target-engaged therapeutic mAb. Immunogenicity assays were based on a
      standard bridge ELISA using the therapeutic antibody for capture and detection.
      Both pharmacokinetic and immunogenicity assays were implemented in preclinical
      studies of the therapeutic antibody. The methods presented here may enable
      further pharmacokinetic studies.

PMID- 21728823
TI  - VEGF expression in hepatectomized tumor-bearing mice.
AB  - The experiments were designed in order to study the VEGF expression in intact
      (group I), hepatectomized (group II), and hepatectomized-tumor bearing mice
      (group III) throughout one complete circadian time span. Adult male mice were
      used for the VEGF expression study. The statistical analysis was performed using
      analysis of variance (ANOVA). The results showed statistical differences in the
      VEGF expression between groups I and II, but the most significant differences
      were found between groups I and III. In conclusion, these expressions have a
      circadian rhythm in all groups; moreover, in group III, this expression was
      higher and appeared before than in the others.

PMID- 21728824
TI  - Antigen heterologous enzyme linked immunosorbent assay for the measurement of
      DHEA in serum.
AB  - Homologous and heterologous combinations of enzyme conjugate and antibody in
      steroid enzyme immunoassay (EIA) influences unlabeled steroid recognition by
      antibody that affects sensitivity of the assay. To develop dehydroepiandrosterone
      (DHEA) antigen heterologous enzyme linked immunosorbent assay (ELISA), antibodies
      were generated against DHEA-3-hemisuccinate-bovine serum albumin (DHEA-3-HS-BSA),
      DHEA-7-carboxymethyloxime-bovine serum albumin (DHEA-7-CMO-BSA), and DHEA-17
      carboxymethyloxime-bovine serum albumin (DHEA-17-CMO-BSA). Five horseradish
      peroxidase (HRP) enzyme conjugates were prepared using five testosterone
      derivatives [testosterone-3-CMO (T-3-CMO), testosterone-17-HS (T-17-HS),
      testosterone-17-glucuronoside (T-17-G), testosterone-19-carboxymethylether (T-19
      CME), and testosterone-11-HS (T-11-HS)]. Fifteen antigen heterologous
      combinations of antibody and enzyme conjugates were evaluated in the standard
      binding assay; only two combinations showed binding. The use of antigen
      heterologous combination (different antigen in label than the immunogen) resulted
      in development of a simple, direct, and convenient assay as it permits the direct
      addition of the serum sample into the assay and it requires only 1.5 h to
      complete.

PMID- 21728825
TI  - CardioDetect rapid test for the diagnosis of early acute myocardial infarction.
AB  - Two hundreds patients suspected of acute myocardial infarction presenting to the
      hospital with a median symptom onset of 2.3 h (IQR 1.7-4.0 h) were enrolled in
      this study. The diagnostic performances of CardioDetect(r), a one-step immunotest
      for heart-type fatty acid-binding protein (H-FABP), and its combination with
      cardiac troponin I (cTnI) at admission and 2 h after admission, were compared
      with different cardiac markers. The H-FABP immunotest had better sensitivities
      (76.6% and 94.4%) than the other cardiac markers and better specificities (88.2%
      and 81.7%) than myoglobin at admission and 2 h after admission. Both sensitivity
      and negative predictive value increased to over 90.0% at 2 h after admission. The
      areas under the receiver operator characteristic curve for the combination of H
      FABP with cTnI were the greatest at admission [0.834 (95% CI: 0.774-0.894)].

PMID- 21728826
TI  - Overexpression of B7-H4 in tumor infiltrated dendritic cells.
AB  - DCs infiltrated tumors appears to be phenotypically and functionally defective.
      B7-H4 was highlighted for its inhibitory role in T cell responses. In this study,
      we showed that B7-H4 was moderately expressed in imDCs, and up-regulated by IL
      10, and TNF-alpha could counteract the up-regulatory effects of IL-10 on
      expression of B7-H4 in DCs in vitro. Furthermore, tumor infiltrated DCs expressed
      B7-H4 at high levels. Blockade of B7-H4 expressed in DCs highly resulted in
      enhanced T cell proliferation and IFN-gamma production significantly. Otherwise,
      the high level of IL-10 and TNF-alpha was both detected in the tumor, which
      suggested that TNF-alpha can not antagonize the effects of IL-10 on expression of
      B7-H4 in DCs in vivo. These data indicate that tumor environment may condition
      local DCs to become dysfunctional in the phenotype, and that the high expression
      of B7-H4 may contribute to the tumor infiltrated DCs to mediate immune invasion.

PMID- 21728828
TI  - A preliminary comparison of verb tense production in Spanish speakers with
      expressive restrictions.
AB  - Spoken verb tense use in three groups of Spanish speakers with expressive
      limitations, namely, children with specific language impairment, bilingual
      children with first language (L1) (Spanish) attrition and adults with
      agrammatism, was compared in order to examine the possible impact of
      conversational tense frequency on expressive production. Based on the notion that
      frequent language forms in typical discourse are preferred in contexts of
      expressive restrictions, we predicted that tenses with high spoken occurrence
      will be favoured by individuals in our expressively limited groups. The incidence
      of tense use by the participants was assessed in oral narratives and/or a
      sentence repetition task. Consistent with our prediction, the most frequent verb
      tenses in conversational Spanish--the present, followed by the preterite--were
      preferred by the participants thus supporting the proposal that a socio-cognitive
      factor linking discursive frequency to verb retrieval may be operating in tense
      preference in situations of expressive stress.

PMID- 21728829
TI  - Cognitive state verbs and complement clauses in children with SLI and their
      typically developing peers.
AB  - This study investigated the use of cognitive state verbs (CSVs) and complement
      clauses in children with specific language impairment (SLI) and their typically
      developing (TD) peers. In Study 1, conversational samples from 23 children with
      SLI (M = 6;2), 24 age-matched TD children (M = 6;2) and 21 vocabulary-matched TD
      children (M = 4;9) were analysed for the proportional use of CSVs, verb types, co
      occurrence with complement clauses and syntactic frame types. Children in all
      three groups had similar performance in all measures. Study 2 compared a subset
      of children on CSV use in conversational and narrative/expository samples.
      Conversation elicited more high-frequency verbs, whereas narrative/expository
      samples elicited more low-frequency verbs. Children with SLI used fewer different
      verbs and were less likely to combine low-frequency verbs with a complement
      clause than their TD peers. We conclude that these observed deficits can be
      attributed to limitations in lexical knowledge rather than a syntactic deficit.

PMID- 21728830
TI  - Age-related differences in idiom production in adulthood.
AB  - To investigate whether idiom production was vulnerable to age-related
      difficulties, we asked 40 younger (ages 18-30) and 40 older healthy adults (ages
      60-85) to produce idiomatic expressions in a story-completion task. Younger
      adults produced significantly more correct idiom responses (73%) than did older
      adults (60%). When older adults generated partially correct responses, they were
      less likely than younger participants to eventually produce the complete target
      idiom (old: 32%; young: 70%); first-word cues after initial failure to retrieve
      an idiom resulted in more correct idioms for older (24%) than younger (15%)
      participants. Correlations between age and idiom correctness were positive for
      the young group and negative for the older group, suggesting mastery of familiar
      idioms continues into adulthood. Within each group, scores on the Boston Naming
      Test correlated with performance on the idiom task. Findings for retrieving
      idiomatic expressions are thus similar to those for retrieving lexical items.

PMID- 21728831
TI  - Production of infinitival complements by children with specific language
      impairment.
AB  - The purpose of this study was to explore the production of infinitival
      complements by children with specific language impairment (SLI) as compared with
      mean length of utterance (MLU)-matched children in an effort to clarify
      inconsistencies in the literature. Spontaneous language samples were analysed for
      infinitival complements (reduced infinitives and true infinitives). Participants
      included children with SLI (n = 19; 5;2-7;10) and children with typical language
      (n = 19; MLU; 3;0-5;9). There was no group difference in the number of
      infinitival complements and the number of different complement-taking verbs.
      However, the SLI group produced more true infinitives than the MLU group. The SLI
      group was less accurate than the MLU group on inclusion of obligatory infinitival
      to, with 80.21% accuracy (SD = 29.42) and 99.81% accuracy (SD = 0.85),
      respectively. As a group, children with SLI did not have problems with the
      clausal structure of infinitives. However, they had difficulty with the specific
      grammatical requirement of infinitival clauses, that is, the inclusion of the
      infinitival marker.

PMID- 21728832
TI  - A procedure for the computerized analysis of cleft palate speech transcription.
AB  - The phonetic symbols used by speech-language pathologists to transcribe speech
      contain underlying hexadecimal values used by computers to correctly display and
      process transcription data. This study aimed to develop a procedure to utilise
      these values as the basis for subsequent computerized analysis of cleft palate
      speech. A computer keyboard file and a modified font file were developed using
      symbols from the International Phonetic Alphabet and extensions to the
      International Phonetic Alphabet to improve the computerized storage of phonetic
      symbols used in cleft palate speech transcription. Computerized coding procedures
      were written to retrieve hexadecimal values of transcribed symbols and match
      these to their phonetic attributes as defined in the International Phonetic
      Alphabet and extensions to the International Phonetic Alphabet. Computerized
      procedures were subsequently developed to analyse transcription data based on
      these matched hexadecimal values and their associated phonetic attributes, with
      respect to cleft palate speech. This method will be a useful addition to existing
      computerized speech analysis tools.

PMID- 21728833
TI  - The effects of macroglossia on speech: a case study.
AB  - This article presents a case study of speech production in a 14-year-old Amharic
      speaking boy. The boy had developed secondary macroglossia, related to a
      disturbance of growth hormones, following a history of normal speech development.
      Perceptual analysis combined with acoustic analysis and static palatography is
      used to investigate the specific articulatory compensations arising from the
      macroglossia. The subset of sounds chosen for study were the denti-alveolar and
      alveolar plosives, fricatives, ejectives, nasal, lateral and trill produced in
      single words, as well as in short phrases. The phonetic analysis revealed both
      spatial and temporal atypicalities in the realisations of the sounds in question.
      Speaking rate was slow relative to his peer's speech and attempts to increase
      speech rate resulted in dysfluent speech. Given the phonological system of
      Amharic, however, the atypical segmental realisations, while reducing both the
      intelligibility and acceptability of the participant's speech production, did not
      result in loss of phonological contrasts.

PMID- 21728834
TI  - Children's development of intonation during the first year of cochlear implant
      experience.
AB  - This article describes the longitudinal development of intonation in 18 deaf
      children who received cochlear implants (CIs) before the age of 3 years and 12
      infants with typical development (TD) who served as controls. At the time their
      implants were activated, the children with CIs ranged in age from 9 to 36 months.
      Cross-group comparisons were made when the children had equivalent amounts of
      robust hearing experience but different chronological ages. This article reports
      the results for the 6-month period ending 9 months after activation of the
      child's device for children with CIs, and the 6-month period ending at 12 months
      of age for TD infants. The findings were compared with a model of early
      intonation development in children with normal hearing. The results indicated
      that all groups progressed through one or more of the stages predicted by the
      normative model. At the end of the study period, however, children who had
      received a CI later than 24 months reached a more mature stage of intonation
      development than younger CI recipients. Moreover, the older CI group reached the
      same stage of development as the TD infants who had 3 additional months of
      language listening experience. The findings suggest that the developmental
      advantage which older children had previously demonstrated shortly after
      activation of their CIs is maintained throughout most or all of the first year of
      CI use.

PMID- 21728835
TI  - Acoustic markers of syllabic stress in Spanish excellent oesophageal speakers.
AB  - The purpose of this investigation is to explore the use by Spanish excellent
      oesophageal speakers of acoustic cues to mark syllabic stress. The speech
      material has consisted of five pairs of disyllabic words which only differed in
      stress position. Total 44 oesophageal and 9 laryngeal speakers were recorded and
      a computerised designed ad hoc perceptual test was run in order to assess the
      accurate realisation of stress. The items produced by eight excellent oesophageal
      speakers with highest accuracy levels in the perception experiment were analysed
      acoustically with Praat, to be compared with the laryngeal control group.
      Measures of duration, fundamental frequency, spectral balance and overall
      intensity were taken for each target vowel and syllable. Results revealed that
      Spanish excellent oesophageal speakers were able to retain appropriate acoustic
      relations between stressed and unstressed syllables. Although spectral balance
      revealed as a strong cue for syllabic stress in the two voicing modes, a
      different hierarchy of acoustic cues in each voicing mode was found.

PMID- 21728836
TI  - Analogy between laryngeal gesture in Mongolian Long Song and supracricoid partial
      laryngectomy.
AB  - This article reports the results of a multiparametrical analysis of Mongolian
      Long Song, characterised by multiple ornamentation and shows the similarities
      between the laryngeal behaviour observed during these ornamentations and the
      compensatory gesture produced by patients after supracricoid partial
      laryngectomy. This study includes (1) a physiological analysis of
      videofiberscopic laryngeal data from a healthy Mongolian singer and from three
      non-singer French-speaking clinical patients; and (2) an acoustical analysis
      (fundamental frequency and intensity). For the singer, the fiberoptic analysis
      showed two main laryngeal behaviours in producing ornamentations: (1) 'lyrical'
      vibratos mobilising the entire laryngeal block; (2) 'Mongolian' trills with
      essentially supraglottic movements, the arytenoids being mobilised independently
      of the rest of the laryngeal block. Patients demonstrated similar aryepiglottic
      trilling to fulfil a function of voicing. The acoustic analysis showed that the
      fundamental frequency and the intensity were in phase for vibrato, contrary to
      the 'Mongolian' trills which were in opposite phase, underlying a change of
      laryngeal vibratory mechanisms.

PMID- 21728837
TI  - SOX trio decrease in the articular cartilage with the advancement of
      osteoarthritis.
AB  - SOX trio (SOX-5, SOX-6, and SOX-9) maintain the chondrocytic phenotypes and are
      vital for chondrogenesis in embryonic development. The purpose of this study is
      to investigate the change in the expression of SOX trio with the advancement of
      osteoarthritis (OA) in human articular cartilage (AC). Human OA samples from
      eight patients were obtained from the distal femoral condyles during total knee
      arthroplasty. Minimally OA cartilage taken from areas with no obvious surface
      defects on lateral condyles was compared with advanced OA cartilage obtained from
      areas within 1 cm of overt lesion located on medial condyle surface. SOX-5, SOX
      6, and SOX-9 gene expressions significantly decreased by 41% (p = 0.047), 46% (p
      = 0.047), and 56% (p = 0.029) in advanced OA area compared with the minimally OA
      area. There was a significant decrease in aggrecan and type II collagen (COL2A1)
      gene expressions by 73% (p = 0.029) and 65% (p = 0.029), respectively, in
      advanced OA area compared with the minimally OA area. From Western blotting and
      immunohistochemistry, SOX-5, SOX-6, SOX-9, type II collagen, and aggrecan protein
      expressions also significantly decreased in advanced OA cartilage compared with
      minimally OA cartilage. DNA methylation study of SOX-9 promoter regions revealed
      no difference in the epigenetic status between the two areas. It is concluded
      that SOX trio gene and protein decreased with advancement of OA in human
      articular cartilage.

PMID- 21728838
TI  - Fine structure of extracellular fibers in primo-nodes and vessels.
AB  - To investigate the extracellular matrices in the primo-nodes (PNs) and vessels
      (PVs) (Bonghan corpuscles and ducts), fine structure of the fibers comprising the
      extracellular matrices was studied in relation to the diameter and the
      periodicity to identify the types of the fibers. Electron micrographs of the
      fibers from the previously published works on the PNs and PVs were analyzed by
      using MATLAB programming and ImageJ software. The extracellular fibrous
      components of the PNs and PVs could be classified generally into two groups--thin
      collagen fibrils and thick non-collagenous wavy bent fibers. The thick bent
      fibers were fibrin-like. The diameters of the thick bent fibers were 30-200 nm
      and they were highly bent. This group included organ surface PNs and lymphatic
      PNs/PVs. The diameters of the collagen fibrils were 30-70 nm. Organ surface,
      heart, and hypodermis PVs were categorized in this group. The periodicity of bent
      fibers in an organ surface PN was 16.1 +/- 0.2 (SE) nm, and the periodicity of
      collagen fibrils in the hypodermis PVs was 37.4 +/- 0.5 (SE) nm. Further
      investigations are required to reveal the physiological implications of the two
      types of fibers in the PNs and PVs.

PMID- 21728840
TI  - Restoration of failing maxillary implant-supported fixed prosthesis with cross
      arch splinted unilateral zygomatic implant: a clinical report.
AB  - Management of one or more failing distal implants in an implant supported fixed
      prosthesis in a completely edentulous maxilla creates a challenging situation.
      Restoring immediate function with additional implants in such a situation can be
      a challenge considering the loss of supporting bone, need for grafting, age, and
      the patient's desire for immediate fixed dental prosthesis. This clinical report
      describes a situation where a zygomatic implant has been placed unilaterally and
      splinted with osseointegrated conventional implants by an immediate fixed
      provisional restoration.

PMID- 21728841
TI  - Copy number variation of the gene NCF1 is associated with rheumatoid arthritis.
AB  - AIMS: The aim of this study was to investigate genetic variants in the gene
      neutrophil cytosolic factor 1 (NCF1) for association with rheumatoid arthritis
      (RA). In rodent models, a single-nucleotide polymorphism (SNP) in Ncf1 has been
      shown to be a major locus regulating severity of arthritis. Ncf1 encodes one of
      five subunits of the NADPH oxidase complex. In humans the genomic structure of
      NCF1 is complex, excluding it from genome-wide association screens and
      complicating genetic analysis. In addition to copy number variation of NCF1,
      there are also two nonfunctional pseudogenes, nearly identical in sequence to
      NCF1. We have characterized copy number variation and SNPs in NCF1, and
      investigated these variants for association with RA. RESULTS: We find that RA
      patients are less likely to have an increased copy number of NCF1, 7.6%, compared
      with 11.6% in controls; p=0.037. We also show that the T-allele of NCF1-339
      (rs13447) is expressed in NCF1 and significantly reduces reactive oxygen species
      production. INNOVATION: This is the first finding of genetic association of NCF1
      with RA. The detailed characterization of genetic variants in NCF1 also helps
      elucidate the complexity of the NCF1 gene. CONCLUSION: These data suggest that an
      increased copy number of NCF1 can be protective against developing RA and add
      support to previous findings of a role of NCF1 and the phagocyte NADPH oxidase
      complex in RA pathogenesis.

PMID- 21728842
TI  - MUC1 and MUC4: switching the emphasis from large to small.
AB  - The MUC1 and MUC4 membrane mucins are each composed of a large alpha (alpha) and
      a small beta (beta) subunit. The alpha subunits are fully exposed at the cell
      surface and contain variable numbers of repeated amino acid sequences that are
      heavily glycosylated. In contrast, the beta subunits are much smaller and are
      anchored within the cell membrane, with their amino-terminal portions exposed at
      the cell surface and their carboxy-terminal tails facing the cytosol. Studies
      over the last several years are challenging the long-held belief that alpha
      subunits play the predominant role in cancer by conferring cellular properties
      that allow tumor cells to evade immune recognition and destruction. Indeed, the
      beta subunits of MUC1 and MUC4 have emerged as oncogenes, as they engage
      signaling pathways responsible for tumor initiation and progression. Thus, a
      switch in the emphasis from the large alpha to the small beta subunits offers
      attractive possibilities for successful clinical application. Such a focus shift
      is further supported by the absence of allelic polymorphism and variable
      glycosylation in the beta subunit as well as by the presence of the beta subunit
      in most MUC1 and MUC4 isoforms expressed by tumors. MUC1alpha, also known as
      CA15.3, is a Food and Drug Administration-approved serum biomarker for breast
      cancer, but its use is no longer recommended by the American Society of Clinical
      Oncology. However, comparison of beta subunit expression in normal and malignant
      breast tissues may offer a novel approach to the exploitation of membrane mucins
      as biomarkers, as MUC1beta-induced gene signatures with prognostic and predictive
      values in breast cancer have been reported. Preclinical studies with peptides
      that interfere with MUC1beta oncogenic functions also look promising.

PMID- 21728843
TI  - Preparation of patient doses of (177)Lu-DOTA-TATE using indigenously produced
      (177)Lu: the Indian experience.
AB  - PURPOSE: (177)Lu (T(1/2) = 6.73 days, E(beta(max)) = 0.497 MeV, E(gamma) = 113
      KeV [6.4%] and 208 KeV [11%])-labeled DOTA-TATE, a somatostatin analog, is
      presently being considered a promising agent for the treatment of patients
      suffering from inoperable neuroendocrine tumors, which overexpress somatostatin
      receptors. The objective of the present work was to develop an optimized protocol
      for the preparation of therapeutic dose of (177)Lu-DOTA-TATE with as high as
      achievable specific activity at the time of its administration, taking into
      account the variable specific activity of (177)Lu available during the
      preparation of the agent. METHODS: (177)Lu labeling of DOTA-TATE was carried out
      using a precalculated amount of DOTA-TATE based on the available specific
      activity of (177)Lu at the time of preparation, keeping a minimum molar ratio of
      [DOTA-TATE]:[Lu] = 4:1, so that (177)Lu-DOTA-TATE could be obtained with highest
      possible specific activity without compromising its radiochemical purity and
      stability. RESULTS: One hundred (100) batches of (177)Lu-DOTA-TATE were prepared
      following this protocol till date at five different nuclear medicine centers of
      India, with a radiochemical purity of 98.25% +/- 1.1% and specific activity of
      32.74-65.49 GBq/MUmol (885-1770 mCi/MUmol). Till date, 250 patient doses of
      (177)Lu-DOTA-TATE have been dispensed and administered in 150 patients suffering
      from various types of neuroendocrine-originated tumors. CONCLUSIONS: The
      developed method ensures that patient doses of (177)Lu-DOTA-TATE could be
      prepared with highest possible specific activity depending upon the available
      specific activity of (177)Lu at the hospital radio-pharmacy.

PMID- 21728845
TI  - Determination and application of cut points for accelerometer-based activity
      counts of activities with differing intensity in pet dogs.
AB  - OBJECTIVE: To investigate whether an accelerometer-based activity monitor could
      be used in pet dogs to differentiate among and delineate the amount of time spent
      in activities of differing intensity. ANIMALS: 104 dogs. PROCEDURES: For the
      first phase of the study, each dog (n = 104) wore an accelerometer-based activity
      monitor and was led through a series of standard activities (recumbency
      [sedentary], walking, and trotting). Receiver operating characteristic curves
      were generated to determine the optimal activity counts for predicting whether a
      dog was sedentary, walking, or trotting. For the second phase of the study, dogs
      (n = 99) wore an activity monitor on their collars continuously for 14 days at
      home; intensity of activity for each dog was classified by use of cut points
      determined on the basis of results obtained during the first phase of the study.
      RESULTS: Analysis of receiver operating characteristic curves indicated that
      there was 100% specificity and 100% sensitivity in distinguishing sedentary
      activity from walking activity and 92% specificity and 92% sensitivity in
      distinguishing trotting activity from walking activity. Analysis of data
      collected during the 14-day period at home indicated that dogs were sedentary
      most of the time (median, 87%; range, 65% to 95%). CONCLUSIONS AND CLINICAL
      RELEVANCE: Counts recorded by an accelerometer-based activity monitor could be
      used to discriminate effectively among standardized activities in pet dogs. There
      is potential for use of the method to improve the ability of clinicians and
      researchers to accurately estimate a pet dog's daily energy requirement.

PMID- 21728846
TI  - Evaluation of primary epidermal lamellar density in the forefeet of near-term
      fetal Australian feral and domesticated horses.
AB  - OBJECTIVE: To investigate the density of the primary epidermal lamellae (PEL)
      around the solar circumference of the forefeet of near-term fetal feral and
      nonferal (ie, domesticated) horses. SAMPLE: Left forefeet from near-term
      Australian feral (n = 14) and domesticated (4) horse fetuses. PROCEDURES: Near
      term feral horse fetuses were obtained from culled mares within 10 minutes of
      death; fetuses that had died in utero 2 weeks prior to anticipated birth date and
      were delivered from live Thoroughbred mares were also obtained. Following
      disarticulation at the carpus, the left forefoot of each fetus was frozen during
      dissection and data collection. In a standard section of each hoof, the stratum
      internum PEL density was calculated at the midline center (12 o'clock) and the
      medial and lateral break-over points (11 and 1 o'clock), toe quarters (10 and 2
      o'clock), and quarters (4 and 6 o'clock). Values for matching lateral and medial
      zones were averaged and expressed as 1 density. Density differences at the 4
      locations between the feral and domesticated horse feet were assessed by use of
      imaging software analysis. RESULTS: In fetal domesticated horse feet, PEL density
      did not differ among the 4 locations. In fetal feral horse feet, PEL density
      differed significantly among locations, with a pattern of gradual reduction from
      the dorsal to the palmar aspect of the foot. The PEL density distribution
      differed significantly between fetal domesticated and feral horse feet.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that PEL density
      distribution differs between fetal feral and domesticated horse feet, suggestive
      of an adaptation of feral horses to environment challenges.

PMID- 21728847
TI  - Effects of two simulated oxytetracycline dosing regimens on horizontal transfer
      of antimicrobial resistance plasmids in an in vitro pharmacodynamic model.
AB  - OBJECTIVE: To evaluate the impact of oxytetracycline exposure on horizontal
      transfer of an antimicrobial resistance plasmid. SAMPLE: Populations of
      Salmonella enterica subsp enterica serovar Typhimurium and Escherichia coli.
      PROCEDURES: Mixed populations of plasmid donor (Salmonella Typhimurium) and
      recipient (E coli) bacteria were assigned to 1 of 2 simulated oxytetracycline
      dosing regimens (high peak concentration-short elimination half-life [HC-SHL] or
      low peak concentration-long elimination half-life [LC-LHL]) or served as
      untreated control replicates. Donor, recipient, and transconjugant (E coli that
      acquired the plasmid) bacteria populations were quantified at 12, 24, and 36
      hours after oxytetracycline administration by use of culture on selective
      bacterial growth media. RESULTS: The ratio of transconjugant to donor bacteria
      was significantly reduced in the oxytetracycline-exposed replicates, compared
      with the ratio for the control replicates, at 12 hours. At 24 and 36 hours,
      results for the HC-SHL regimens were not significantly different from results for
      the respective control replicates, and results for the LC-LHL regimens also were
      not significantly different from results for the respective control replicates.
      The oxytetracycline concentration at these time points (12 hours in the HC-SHL
      regimen and all 3 time points in the LC-LHL regimen) were in excess of the
      minimum inhibitory concentration of the recipient bacteria. CONCLUSIONS AND
      CLINICAL RELEVANCE: Transfer of antimicrobial resistance plasmids may be
      suppressed in vitro by oxytetracycline exposure at concentrations greater than
      the minimum inhibitory concentration of the recipient bacteria.

PMID- 21728848
TI  - Chondrogenic effects of exogenous retinoic acid or a retinoic acid receptor
      antagonist (LE135) on equine chondrocytes and bone marrow-derived mesenchymal
      stem cells in monolayer culture.
AB  - OBJECTIVE: To determine effects of various concentrations of retinoic acid (RA)
      or a synthetic RA receptor antagonist (LE135) on equine chondrocytes or bone
      marrow-derived equine mesenchymal stem cells (BMDMSCs) in monolayer cultures.
      SAMPLE: Articular cartilage and BMDMSCs from 5 clinically normal horses.
      PROCEDURES: Monolayers of chondrocytes cultured in standard media and of BMDMSCs
      cultured in chondrogenic media were treated with RA at concentrations of 0, 0.1,
      1, or 10 MUM or LE135 at concentrations of 0, 0.1, 1, or 10 MUM on day 0. On days
      7 and 14, samples were analyzed for DNA concentration, chondrocyte morphology or
      features consistent with chondrogenesis (ie, chondral morphology [scored from 0
      to 4]), and gene expression of collagen type Ia (CI), collagen type II (CII), and
      aggrecan. RESULTS: Chondrocytes treated with RA had more mature chondral
      morphology (range of median scores, 3.0 to 4.0) than did untreated controls
      (range of median scores, 0.5 to 0.5). Chondrocytes treated with LE135 did not
      sustain chondrocyte morphology. All BMDMSCs had evidence of chondral morphology
      or high CII:CI ratio. Retinoic acid (1 or 10 MUM) or LE135 (10 MUM) treatment
      decreased DNA content of BMDMSC cultures. At 0.1 and 1 MUM concentrations, LE135
      weakly but significantly increased chondral morphology scores, compared with
      untreated controls, but lack of aggrecan expression and lack of increased CII:CI
      ratio, compared with that of controls, did not affect chondrogenesis. CONCLUSIONS
      AND CLINICAL RELEVANCE: RA promoted maturation and hypertrophy in chondrocytes
      but not BMDMSCs in monolayer cultures. Deficiency or blockade of RA may prevent
      hypertrophy and maturation of differentiated chondrocytes.

PMID- 21728849
TI  - Evaluation of intervertebral disk degeneration in chondrodystrophic and
      nonchondrodystrophic dogs by use of Pfirrmann grading of images obtained with low
      field magnetic resonance imaging.
AB  - OBJECTIVE: To assess whether the Pfirrmann system for grading lumbar
      intervertebral disk (IVD) degeneration in humans can also be used in dogs.
      ANIMALS: 202 dogs. PROCEDURES: Magnetic resonance imaging was used to obtain
      images of vertebral segments from dogs, which were reviewed separately by 3
      observers who graded the extent of degeneration in each visible IVD by use of the
      Pfirrmann classification system used for grading lumbar IVD degeneration in
      humans. Grading was validated against 2 factors associated with the extent of
      disk degeneration: type of dog (chondrodystrophic or nonchondrodystrophic breeds)
      and age. RESULTS: Interobserver and intraobserver agreement for Pfirrmann grading
      of IVD degeneration were good (kappa scores, 0.81 to 0.93). An increase in the
      extent of disk degeneration was positively correlated with increases in age and
      with chondrodystrophic breed. CONCLUSIONS AND CLINICAL RELEVANCE: The Pfirrmann
      system was reliably used to grade IVD degeneration in dogs of various breeds and
      ages. An increase in the extent of IVD degeneration was positively correlated
      with increases in age and with chondrodystrophic-type dogs.

PMID- 21728850
TI  - Reliability of macroscopic grading of intervertebral disk degeneration in dogs by
      use of the Thompson system and comparison with low-field magnetic resonance
      imaging findings.
AB  - OBJECTIVE: To evaluate the reliability of the Thompson system for use in grading
      the gross pathological changes of intervertebral disk (IVD) degeneration in dogs
      and to investigate the agreement between gross pathological findings and low
      field (0.2-T) magnetic resonance imaging (MRI) findings. SAMPLE: Vertebral
      columns from cadavers of 19 dogs of various ages, breeds, and origins.
      PROCEDURES: 182 intervertebral segments were collected from 19 canine cadavers.
      Sagittal T2-weighted MRI of the T11 through S1 portion of the vertebral column
      was performed within 24 hours after the dogs were euthanized. The vertebral
      columns were subsequently divided in the midsagittal plane, and high-resolution
      photographs were obtained of each intervertebral segment (end plate-disk-end
      plate). The MRI images and photographs were graded separately in a blinded manner
      by 4 observers who used both Pfirrmann and Thompson grading criteria. RESULTS:
      The interobserver agreement for Thompson scores ranged from 0.76 to 0.88, and the
      intraobserver agreement ranged from 0.88 to 0.94 (Cohen weighted kappa analysis).
      Agreement between scores for the Pfirrmann and Thompson grading criteria was
      kappa = 0.70. CONCLUSIONS AND CLINICAL RELEVANCE: Grading of IVD degeneration in
      dogs by use of the Thompson system resulted in high interobserver and
      intraobserver agreement, and scores for the Thompson system had substantial
      agreement with low-field MRI findings graded by use of the Pfirrmann system. This
      suggested that low-field MRI can be used to diagnose IVD degeneration in dogs.

PMID- 21728851
TI  - Effects of body position, imaging plane, and observer on computed tomographic
      measurements of the lumbosacral intervertebral foraminal area in dogs.
AB  - OBJECTIVE: To evaluate effects of imaging plane, flexion and extension, patient
      weight, and observer on computed tomographic (CT) image measurements of the area
      of the lumbosacral (L7-S1) intervertebral foramen (LSIF) in dogs. SAMPLE: 12 dog
      cadavers (2 were excluded because of foraminal stenosis). PROCEDURES: In each
      cadaver, sagittal, sagittal oblique, transverse oblique, and double oblique CT
      images were obtained at 3 zones (entrance, middle, and exit zones) of the region
      of the lateral lumbar spinal canal that comprises the LSIF while the lumbosacral
      junction (LSJ) was positioned in flexion or extension. Barium-impregnated
      polymethylmethacrylate was used to fill the intervertebral foramina to aid
      boundary detection. Measurements of interest were obtained. RESULTS: Among the
      dog cadavers, there was large variability in LSIF cross-sectional areas (range,
      0.12 to 0.44 cm2; SD, 0.1 cm2) and in foraminal angles required to obtain a
      double oblique plane in LSJ extension (SD, 8  degrees  to 9  degrees ). For LSIF
      area measurements in standard sagittal CT images, interobserver variability was
      23% to 44% and intraobserver variability was 4% to 5%. Sagittal oblique images
      obtained during LSJ extension yielded smaller mean LSIF areas (0.30 cm2),
      compared with findings in sagittal images (0.37 to 0.52 cm2). The exit and middle
      zone areas were smaller than the entrance zone area in sagittal images obtained
      during LSJ extension. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated measurements
      of the LSIF area in images obtained during LSJ extension may be unreliable as a
      result of interobserver variability and the effects of dog positioning and CT
      slice orientation.

PMID- 21728852
TI  - Effect of water content in a canned food on voluntary food intake and body weight
      in cats.
AB  - OBJECTIVE: To determine whether water content in a canned food diet induces
      decreases in voluntary energy intake (EI) or body weight (BW) in cats fed ad
      libitum. ANIMALS: 16 sexually intact male domestic shorthair cats. PROCEDURES:
      Maintenance EI was determined for 2 months in 10 weight-stable cats consuming a
      control diet (typical colony diet). Cats were allocated into 2 groups of equal BW
      and fed a canned diet (with-water [WW] diet) or a freeze-dried version of the
      canned diet (low-water [LW] diet) twice daily. Diets were identical in nutrient
      profile on a dry-matter basis. Each dietary treatment period of the crossover
      experiment lasted 3 weeks, with a 3-week washout period between diets. Body
      composition measurements were determined by use of deuterium oxide at the end of
      each dietary treatment. Daily food intake was measured for determination of dry
      matter intake and EI. Six other cats were used in preference tests for the 3
      diets. RESULTS: EI was significantly decreased for the WW diet (mean +/- SD,
      1,053.0 +/- 274.9 kJ/d), compared with EI for the LW diet (1,413.8 +/- 345.8
      kJ/d). Cats had a significant decrease in BW during consumption of the WW diet.
      Body composition was unaltered by diet. In short-term preference tests, cats ate
      significantly more of the WW than the LW diet. CONCLUSIONS AND CLINICAL
      RELEVANCE: Bulk water in the WW diet stimulated decreases in EI and BW in cats.
      The impact of water content on energy density and food consumption may help
      promote weight loss in cats.

PMID- 21728853
TI  - Characterization of the risk of deer-cattle interactions in Minnesota by use of
      an on-farm environmental assessment tool.
AB  - OBJECTIVE: To characterize the risk of interactions that may lead to the
      transmission of Mycobacterium bovis between cattle and white-tailed deer
      (Odocoileus virginianus) on farms in northern Minnesota. SAMPLE: 53 cattle farms
      in northwestern Minnesota adjacent to an area where bovine tuberculosis-infected
      cattle and deer were detected. PROCEDURES: A semiquantitative deer-cattle
      interaction assessment tool was used for the 53 cattle herds. Farm risk scores
      were analyzed on the basis of deer damage to stored feed. RESULTS: 27 (51%) farms
      reported deer damage to stored cattle feeds within the year previous to the farm
      visit. A strong association was found between increases in the percentage of land
      that could serve as deer cover and deer damage to stored feeds on a farm. The
      total risk score was significantly associated with the probability of a farm
      having deer damage. By use of a logistic regression model, the total risk score
      and proportion of nonagricultural land around a farm could be used to predict the
      likelihood of deer damage to stored feeds. CONCLUSIONS AND CLINICAL RELEVANCE:
      Management practices on many farms in northwestern Minnesota allowed potential
      deer-cattle interactions. The on-farm risk assessment tool served as a valuable
      tool for prioritizing the biosecurity risks for farms. Continued development of
      biosecurity is needed to prevent potential transmission of bovine tuberculosis
      between deer and cattle, especially on farms that have a higher risk of deer
      damage.

PMID- 21728854
TI  - Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with
      dilated cardiomyopathy.
AB  - OBJECTIVE: To identify a causative mutation for dilated cardiomyopathy (DCM) in
      Doberman Pinschers by sequencing the coding regions of 10 cardiac genes known to
      be associated with familial DCM in humans. ANIMALS: 5 Doberman Pinschers with DCM
      and congestive heart failure and 5 control mixed-breed dogs that were euthanized
      or died. PROCEDURES: RNA was extracted from frozen ventricular myocardial samples
      from each dog, and first-strand cDNA was synthesized via reverse transcription,
      followed by PCR amplification with gene-specific primers. Ten cardiac genes were
      analyzed: cardiac actin, alpha-actinin, alpha-tropomyosin, beta-myosin heavy
      chain, metavinculin, muscle LIM protein, myosinbinding protein C, tafazzin, titin
      cap (telethonin), and troponin T. Sequences for DCM-affected and control dogs and
      the published canine genome were compared. RESULTS: None of the coding sequences
      yielded a common causative mutation among all Doberman Pinscher samples. However,
      3 variants were identified in the alpha-actinin gene in the DCM-affected Doberman
      Pinschers. One of these variants, identified in 2 of the 5 Doberman Pinschers,
      resulted in an amino acid change in the rod-forming triple coiled-coil domain.
      CONCLUSIONS AND CLINICAL RELEVANCE: Mutations in the coding regions of several
      genes associated with DCM in humans did not appear to consistently account for
      DCM in Doberman Pinschers. However, an alpha-actinin variant was detected in some
      Doberman Pinschers that may contribute to the development of DCM given its
      potential effect on the structure of this protein. Investigation of additional
      candidate gene coding and noncoding regions and further evaluation of the role of
      alpha-actinin in development of DCM in Doberman Pinschers are warranted.

PMID- 21728855
TI  - Inheritance of cerebellar abiotrophy in Arabians.
AB  - OBJECTIVE: To determine the mode of inheritance for cerebellar abiotrophy (CA), a
      neurologic disease in Arabians. ANIMALS: 804 Arabians, including 29 horses (15
      males and 14 females) with CA. PROCEDURES: Most horses (n = 755) belonged to 1 of
      4 paternal families. Among the 29 CA-affected horses, all had clinical signs
      consistent with the disease; the disease was confirmed histologically following
      euthanasia in 8 horses. From the pedigree information, inbreeding coefficients
      were calculated for 16 affected horses and compared with coefficients for a
      subgroup of 16 unaffected horses. Complex segregation analysis was used to
      determine the effect of a putative Mendelian locus on the development of the
      disease and the probable mode of inheritance of CA. RESULTS: The mean inbreeding
      coefficient was 0.0871 for CA-affected and unaffected horses, suggesting that all
      of the Arabians were inbred to the same degree and that affected horses were not
      more inbred than were unaffected horses. Results of the complex segregation
      analysis were consistent with a single Mendelian autosomal recessive mode of
      inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of the mode of
      inheritance of CA should help breeders to make informed decisions regarding the
      selection of animals for mating when closely related horses have developed CA or
      produced CA-affected foals.

PMID- 21728856
TI  - Evaluation of the efficacy of gallium maltolate for chemoprophylaxis against
      pneumonia caused by Rhodococcus equi infection in foals.
AB  - OBJECTIVE: To determine the chemoprophylactic effect of gallium maltolate on the
      cumulative incidence of pneumonia caused by Rhodococcus equi infection in foals.
      ANIMALS: 483 foals born and raised on 12 equine breeding farms with a history of
      endemic R equi infections. PROCEDURES: Group 1 foals were treated with a placebo
      and group 2 foals were treated with gallium maltolate (approx 30 mg/kg, PO, q 24
      h) during the first 2 weeks after birth. Foals were monitored for development of
      pneumonia attributable to R equi infection and for adverse effects of gallium
      maltolate. RESULTS: There were no significant differences in the cumulative
      incidence of R equi pneumonia among the 2 groups. CONCLUSIONS AND CLINICAL
      RELEVANCE: Chemoprophylaxis via gallium maltolate administered orally at
      approximately 30 mg/kg daily for the first 2 weeks after birth failed to reduce
      the cumulative incidence of pneumonia attributable to R equi infection among
      foals on breeding farms with endemic R equi infections. Further investigation is
      needed to identify strategies for control of R equi infections.

PMID- 21728857
TI  - Radiographic vertebral canal and vertebral body ratios in Doberman Pinschers with
      and without clinical signs of caudal cervical spondylomyelopathy.
AB  - OBJECTIVE: To determine radiographic vertebral ratio values representing
      vertebral canal stenosis in Doberman Pinschers with and without clinical signs of
      caudal cervical spondylomyelopathy (CCSM). ANIMALS: Doberman Pinschers with (n =
      81) and without (39) signs of CCSM. PROCEDURES: All dogs underwent lateral survey
      radiography of the cervical vertebral column. Five specific measurements were
      made at C3 through C7, and from those data, 3 ratios were calculated and analyzed
      for use in diagnosis of CSSM: canal height-to-vertebral body height ratio (CBHR),
      canal height-to-vertebral body length ratio (CBLR), and caudal vertebral canal
      height-to-cranial vertebral canal height ratio (CCHR). The CBHR and CBLR were
      considered indicators of vertebral canal stenosis, and CCHR described vertebral
      canal shape. RESULTS: Compared with Doberman Pinschers without CCSM, mean CBHR
      and CBLR values were significantly smaller for Doberman Pinschers with CCSM; for
      CBHR, this difference was evident at each assessed vertebra. The CCHR value for
      C7 was significantly larger in dogs with CCSM. Receiver operating characteristic
      statistics did not identify a threshold point that had combined high sensitivity
      and specificity sufficient to differentiate between Doberman Pinschers with and
      without CCSM. CONCLUSIONS AND CLINICAL RELEVANCE: Doberman Pinschers with CCSM
      had vertebral canal stenosis combined with a funnel-shaped vertebral canal at C7
      significantly more often than did Doberman Pinschers without CCSM. Despite these
      significant differences, no reliable threshold ratio values were identified to
      differentiate groups of dogs.

PMID- 21728858
TI  - Pharmacokinetics of tramadol and metabolites O-desmethyltramadol and N
      desmethyltramadol in adult horses.
AB  - OBJECTIVE: To determine the pharmacokinetics of tramadol and its metabolites O
      desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses. ANIMALS:
      12 mixed-breed horses. PROCEDURES: Horses received tramadol IV (5 mg/kg, over 3
      minutes) and orally (10 mg/kg) with a 6-day washout period in a randomized
      crossover design. Serum samples were collected over 48 hours. Serum tramadol,
      ODT, and NDT concentrations were measured via high-performance liquid
      chromatography and analyzed via noncompartmental analysis. RESULTS: Maximum mean
      +/- SEM serum concentrations after IV administration for tramadol, ODT, and NDT
      were 5,027 +/- 638 ng/mL, 0 ng/mL, and 73.7 +/- 12.9 ng/mL, respectively. For
      tramadol, half-life, volume of distribution, area under the curve, and total body
      clearance after IV administration were 2.55 +/- 0.88 hours, 4.02 +/- 1.35 L/kg,
      2,701 +/- 275 h x ng/mL, and 30.1 +/- 2.56 mL/min/kg, respectively. Maximal serum
      concentrations after oral administration for tramadol, ODT, and NDT were 238 +/-
      41.3 ng/mL, 86.8 +/- 17.8 ng/mL, and 159 +/- 20.4 ng/mL, respectively. After oral
      administration, half-life for tramadol, ODT, and NDT was 2.14 +/- 0.50 hours,
      1.01 +/- 0.15 hours, and 2.62 +/- 0.49 hours, respectively. Bioavailability of
      tramadol was 9.50 +/- 1.28%. After oral administration, concentrations achieved
      minimum therapeutic ranges for humans for tramadol (> 100 ng/mL) and ODT (> 10
      ng/mL) for 2.2 +/- 0.46 hours and 2.04 +/- 0.30 hours, respectively. CONCLUSIONS
      AND CLINICAL RELEVANCE: Duration of analgesia after oral administration of
      tramadol might be < 3 hours in horses, with ODT and the parent compound
      contributing equally.

PMID- 21728859
TI  - Characterization of the responses of equine digital veins and arteries to
      calcitonin gene-related peptide.
AB  - OBJECTIVE: To compare responses of equine digital arteries (EDAs) and veins
      (EDVs) to human-alphacalcitonin gene-related peptide (halphaCGRP), evaluate
      effect of the endothelium, and characterize receptors and sources of endogenous
      CGRP. SAMPLE: Palmar digital vessels (5 to 9/experiment) from healthy adult
      horses killed at an abattoir. PROCEDURES: Vessel rings were mounted under tension
      in organ baths containing Krebs-Henseleit solution at 30  degrees C, with
      relaxation responses examined in vessels preconstricted with a thromboxane
      mimetic (3 * 10(-8)M). Responses of endothelium-intact (+e) and -denuded (-e)
      EDAs and EDVs to halphaCGRP C10(-10) to 3 * 10(-7)M) were compared. Following
      incubation with an halphaCGRP receptor antagonist (halphaCGRP(8-37); 1 MUM),
      responses of EDA(-e) and EDV(-e) to halphaCGRP (10(-7)M) were obtained. Responses
      of endothelium-intact and -denuded arteries and veins to halphaCGRP (3 * 10(-7)M)
      or capsaicin (10(-5)M) were evaluated as well as responses of endothelium-intact
      and -denuded EDA and EDV to halphaCGRP (10(-10) to 10(-6)M) after incubation with
      endothelin-1 (ET-1; 10(-12)M). RESULTS: halphaCGRP resulted in nonendothelium,
      concentration-dependent relaxation in EDAs and EDVs, with greater responses in
      EDAs. Treatment with halphaCGRP(8-37) had minimal effect on responses to
      halphaCGRP in either vessel type. Capsaicin induced relaxation in both vessel
      types. There were no differences between responses to halphaCGRP for vessels
      pretreated with ET-1 or vehicle. CONCLUSIONS AND CLINICAL RELEVANCE: Both
      halphaCGRP and capsaicin induced digital vasodilation unaffected by a functional
      endothelium. This suggested that endogenous CGRP likely emanates from sensory
      motor nerves and may contribute to digital vasodilation.

PMID- 21728860
TI  - In vitro and in vivo responses of mucosa from the large colon of horses to
      ischemia and reperfusion.
AB  - OBJECTIVE: To induce ischemia and reperfusion injury in the large colon mucosa of
      horses in vivo and evaluate the recovery and effects of components of an organ
      transplant solution on mucosal recovery in vitro. ANIMALS: 6 healthy horses.
      PROCEDURES: Horses were anesthetized, and ischemia was induced for 60 minutes in
      the pelvic flexure, which was followed by reperfusion for 240 minutes. Ischemic
      (n = 4 horses), reperfused (6), and adjacent control (6) colonic mucosae were
      isolated for in vitro testing and histologic examinations. Tissues were mounted
      in Ussing chambers with plain Krebs Ringer bicarbonate (KRB), KRB with N
      acetylcysteine (NAC), or KRB with a modified organ transplant solution (MOTS).
      Transepithelial electrical resistance (TER) and mannitol flux were used to assess
      mucosal integrity. Data were analyzed by use of ANOVA and Kruskal-Wallis tests.
      RESULTS: The TER in reperfused tissues was similar to the TER in control tissues
      and greater than the TER in ischemic tissues, which was consistent with
      morphological evidence of recovery in reperfused tissues. Mannitol flux was
      greater in ischemic tissues than in reperfused tissues. The TER and mannitol flux
      were not significantly affected by incubation of mucosa with NAC or MOTS.
      CONCLUSIONS AND CLINICAL RELEVANCE: Ischemia induced during the brief period
      allowed rapid mucosal repair and complete recovery of tissue barrier properties
      during reperfusion. Therefore, reperfusion injury was not observed for this
      method of ischemic damage in equine colonic mucosa.

PMID- 21728861
TI  - An algorithm for detecting high frequency copy number polymorphisms using SNP
      arrays.
AB  - We present a general algorithm for the detection of genomic variants using the
      Illumina iSelect platform. The Illumina iSelect platform is designed to detect
      SNPs, but our algorithm allows for the detections of more general forms of
      variations, including copy number polymorphisms and microsatellites. The
      algorithm does not rely on a priori information of the type of polymorphism being
      studied and is designed to genotype call a large number of individuals
      simultaneously. The algorithm proceeds by initially normalizing intensity and
      correcting for batch effects. Then each marker is clustered using a modified
      Gaussian mixture model where we account for variances in the expression of an
      individuals and the variance measured in bead level intensities of a probe/marker
      pair. Finally, these clusters are used to determine genotypes. The algorithm was
      then run on a dataset of 35,000 Icelandic individuals.

PMID- 21728862
TI  - Tracing the most parsimonious indel history.
AB  - Sequence alignment (the grouping of homologous bases into one column) is
      fundamental to almost any task in comparative genomics. This translates to
      positing gaps in the genomic sequences to account for events of insertions and
      deletions (indels). The interrelationship between sequence alignment and
      phylogenetic reconstruction has drawn substantial attention recently with works
      showing the significance of differences in alignments. One of the plausible
      approaches in this direction is to grade the suitability of a tree to an
      associated alignment and vice verse. We here present a combinatorial (as opposed
      to statistical) approach based on the indel history. We show--both by simulations
      and by using real biological data from the Encyclopedia of DNA Elements (ENCODE)-
      that this criterion is sound. The novelty of our approach is the distinguishing
      between insertions and deletions, and augmenting the analysis with a dimension of
      "depth," extending it from the sequence space to the phylogenetic space. Using
      this approach, we perform a comprehensive study of indel characteristic behavior
      among mammals in both coding and non-coding regions. Our results show significant
      differences in indel patterns between coding and non-coding regions. We also show
      other characteristic patterns of indel evolution in the depth of the underlying
      phylogeny.

PMID- 21728864
TI  - How articles get into The Angle Orthodontist.

PMID- 21728863
TI  - Sabbaticals, self-assembly, and astrobiology.

PMID- 21728867
TI  - From Kentucky to the Caribbean - and the future of federally funded agricultural
      safety and health.

PMID- 21728868
TI  - Determinants of work hours among a cohort of male and female farmers 50 years and
      older in Kentucky and South Carolina (2002-2005).
AB  - The average age of United States farmers has been increasing for 20 years. The
      objective is to examine the factors associated with hours worked among farmers
      age 50 and older. A cohort of Kentucky and South Carolina farmers (n = 1394) over
      age 50 were surveyed annually during 2002-2005. Of those that reported any farm
      work, males worked 24 mean hours/week and females worked 14 mean hours/week.
      Greater satisfaction and more experience farming, increased acreage, and presence
      of animals significantly increased estimated hours farmed, whereas chronic health
      problems, although prevalent, had a minor role in determining work hours.

PMID- 21728869
TI  - Compliance with the North American Guidelines for Children's Agricultural Tasks
      (NAGCAT) work practice recommendations for youth working with large animals.
AB  - The North American Guidelines for Children's Agricultural Tasks (NAGCAT) were
      developed to reduce the risk of childhood agricultural injury. The purpose of
      this study was to evaluate compliance with NAGCAT-recommended work practices
      (WPs) when youth work with large animals. On a daily basis, over a period of 10
      weeks, youth self-reported the number of minutes they worked with a large animal
      and whether they followed the associated NAGCAT WP guidelines. Statistical
      analyses were conducted to compare boys to girls and to consider the effect of
      factors such as youth age, farm residence status, and selected parental
      characteristics. A high proportion of youth exhibited relatively low compliance
      for most of the five WPs evaluated. Respirators were rarely worn, but checking
      for people and obstacles in the area while working with large animals was
      commonly reported. In general, boys, especially the older boys, exhibited higher
      compliance than did girls. The results of our study demonstrate, in general, that
      youth are not following recommended NAGCAT WPs when working with large animals,
      identifying an area in agricultural safety and health requiring focused
      attention.

PMID- 21728870
TI  - Serological evidence of hantavirus infection in farm and abattoir workers in
      Trinidad--a preliminary study.
AB  - Hantaviruses are established causative agents of hemorrhagic fevers and renal
      diseases amongst other clinical manifestations in humans, with most diagnosis
      based on serological assays. The disease, which is rodent-borne, has been
      reported in numerous countries worldwide but information about the disease is
      scanty in the Caribbean. The objective of this investigation is to determine the
      frequency of exposure to hantaviruses in a selected apparently healthy human
      population associated with abattoirs and livestock farms in Trinidad using a
      hantavirus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Of a
      total of 236 individuals tested, 27 (11.4%) were seropositive for hantavirus
      infection. Amongst abattoir workers the frequency of infection was 9.4% (6 of 64)
      compared with seropositivity rate of 12.4% (18 of 145) and 11.1% (3 of 27)
      amongst livestock farm workers and office workers and other individuals with
      minimal animal contact respectively. The differences were, however, not
      statistically significant (p > .05; chi(2) test). Age, gender, and race did not
      significantly affect the infection rate by hantavirus in the workers studied.
      This is considered the first documented evidence of hantavirus infection in
      Trinidad and Tobago. It is imperative for local physicians to consider hantavirus
      as a differential diagnosis in patients with hemorrhagic fever and renal
      diseases, since there may be a number of undiagnosed cases of hantavirus disease
      in the human population in the country.

PMID- 21728871
TI  - Frequency of detection of immunoglobulins of Toxoplasma gondii, Leptospira spp.,
      and Brucella abortus in livestock/farm and abattoir workers in Trinidad.
AB  - Toxoplasma gondi, Leptospira spp., and Brucella abortus are all established
      parasitic and bacterial zoonoses that manifest themselves in several forms of
      human diseases. They have been associated with occupational exposures,
      particularly amongst workers associated with livestock farms. The primary
      objectives of this study were to determine the seroprevalence of T. gondii
      immunoglobulin M (IgM) immunoglobulins (serum antibodies), Leptospira IgM
      immunoglobulins, and B. abortus IgG immunoglobulins, suggestive of acute or
      chronic infections, in livestock/farm and abattoir workers in Trinidad, and to
      relate to risk factors. Blood samples were collected from 394 consenting
      livestock/farm workers and 99 abattoir workers across the island of Trinidad.
      Serological status was determined by enzyme immunoassay (EIA) for T. gondii IgM,
      enzyme-linked immunosorbent assay (ELISA) for Leptospira IgM immunoglobulins, and
      buffered plate agglutination test (BPAT) and competitive ELISA for B. abortus IgG
      immunoglobulins. Of 394 apparently healthy livestock/farm workers sampled, 150
      (38.1%) were seropositive for T. gondii IgM immunoglobulins, compared with 44
      (44.4%) of 99 abattoir workers (p > .05; chi(2) test). Five (1.3%) of 371 and 1
      (1.0%) of 99 livestock/farm and abattoir workers respectively were positive for
      Leptospira IgM immunoglobulins. All samples from livestock/farm workers and
      abattoir workers were negative for B. abortus immunoglobulins. None of the risk
      factors investigated was statistically significantly (p > .05; chi(2) test)
      associated with T. gondii and Leptospira spp. infections.

PMID- 21728872
TI  - Secondary injury potential of assistive technologies used by farmers with
      disabilities: findings from case studies.
AB  - In order to complete essential tasks, farmers with disabilities often make and
      use assistive technology (AT), which itself may cause further injuries known as
      secondary injuries. A set of 19 case studies was used to investigate the
      potential for injury on home-fabricated assistive technologies (ATs) used by
      farmers with disabilities. The case studies consisted of close-ended and open
      ended interviews that were designed to help understand the farmers' perception of
      potential for injuries and safety measures implemented or not implemented. The
      qualitative study used grounded theory principles and the collected data were
      analyzed to arrive at a list of features on ATs that have substantial potential
      to cause injury to the user. Based on the case study results, AT user
      characteristics and environmental factors were also considered as factors that
      contribute to potential injuries. Findings were used to develop an instrument for
      use by rehabilitation professionals to evaluate ATs for potential injury causing
      hazards.

PMID- 21728873
TI  - An exploratory pilot study of childhood injuries on cattle farms in Jalisco,
      Mexico.
AB  - Childhood agricultural injuries have been a concern in the United States for many
      years. Much research has been performed on the cause and prevention of such
      injuries. The North American Guidelines for Children's Agricultural Tasks
      (NAGCAT) have been developed in the United States to address the common
      agricultural tasks and injuries sustained by children. Data are lacking
      concerning the common agricultural tasks and injuries of children working on
      Mexican farms. The goal of the study was to determine if the NAGCAT guidelines
      developed for the United States may be applicable to children in Jalisco, Mexico.
      Interviews of local physicians were performed regarding their perception of
      common childhood agricultural injuries. Interviews about common childhood
      agricultural tasks and injuries were performed at 27 farms through the help of a
      local cooperative. Work practices at these farms were also observed. Emergency
      department records were reviewed for childhood agricultural injuries. Surveys of
      local cattle farms revealed the most common childhood agricultural tasks were
      feeding animals, milking cows, and cleaning corrals. Through the same cattle farm
      interviews, the most common childhood agricultural injuries included being kicked
      by an animal, scorpion bites, cuts, and falls. Physician interviews revealed
      machinery, poisonings, cuts, and lacerations as the most common injuries. Due to
      the lack of adequate documentation, the emergency department medical record
      review was not useful. The NAGCAT guidelines address many of the common tasks and
      injuries in the Tepatitlan area, including animal care, operating machinery, and
      cleaning corrals. There are other common injuries in the Tepatitlan area such as
      scorpion bites for which no NAGCAT guidelines currently exist but for which
      guidelines could be developed. Once translated to Spanish and adjusted for
      cultural relevancy, the NAGCAT guidelines would address many of the common
      agricultural tasks and injuries of children in Jalisco, Mexico.

PMID- 21728878
TI  - Neospora caninum is associated with abortion in Algerian cattle.
AB  - Neospora caninum is a major cause of abortion in cattle worldwide. However,
      little information is available for Algeria. Accordingly, 799 cattle from 87
      farms in the north and northeast of Algeria were enrolled in a
      seroepidemiological survey. An indirect fluorescence antibody test (IFAT)
      revealed a seroprevalence of 19.6%. The animals were divided into 3 groups
      according to their breed: imported European cattle, local breeds, and crossed
      animals (European * local). Seroprevalences were 16.0%, 34.3%, and 18.6% in
      groups 1, 2, and 3, respectively. A case control study was performed to
      investigate the link between global seropositivity to N. caninum and abortion
      risk in those cattle farms. There was a significant (P < 0.01) association
      between the seroprevalence against N. caninum and the occurrence of abortion in
      those farms (odds ratio [OR]  =  12.03). This was also observed at the individual
      level (OR  =  2.79). The analysis of results according to the breed revealed a
      significant association between seroprevalence and abortion in groups 1 and 3,
      but not for group 2, despite the fact that the highest seroprevalence was
      observed in group 2. Cerebral tissues from 5 aborted fetuses were available for
      histology and polymerase chain reaction (PCR). One sample was found positive both
      by histology and by PCR, 2 samples were positive by PCR only, and 2 samples were
      negative in both tests.

PMID- 21728880
TI  - A population-based assessment of midlife Portuguese women's experience of
      perimenopause and menopause.
AB  - The frequency of changes experienced by menopausal women is variable in different
      cultures. It is our purpose to identify the symptoms that Portuguese women
      consider to be related to menopause. We also wish to evaluate the relations
      between these symptoms and menopausal status, sociodemographic and lifestyle
      factors, and medication-menopausal hormone therapy (MHT) and psychotropics. In
      women with a low educational level, the frequency of symptoms and the consumption
      of psychotropic medication is higher, and the practice of exercise is lower, as
      is the use of MHT. Our results may be useful in providing guidance to health care
      professionals.

PMID- 21728881
TI  - Factors associated with female provider preference among African American women,
      and implications for breast cancer screening.
AB  - Globally, breast cancer incidence is increasing. Early detection remains
      important for addressing disparities, including among U.S. minorities. Seeing a
      female physician increases screening, but the effects of unmet provider gender
      preference among underserved populations remain unexplored. Among 576 urban
      African American women age 45-93, we examined predictors of gender preference and
      how met and unmet preference influenced screening. We conclude that provider
      gender is a "double-edged sword." We saw a female provider screening benefit, but
      also that gender preference was associated with past disadvantage and attitudes
      inconsistent with health maintenance. Provider gender preference merits further
      consideration in women's health research.

PMID- 21728882
TI  - Translation and adaptation of the life stressor checklist-revised with Colombian
      women.
AB  - We undertook the translation and adaptation of an instrument developed to measure
      women's lifetime trauma exposure, the Life Stressor Checklist-Revised (LSC-R), in
      order to determine its utility and cultural appropriateness with Colombian
      Spanish-speaking women. The LSC-R was forward and backward translated and
      administered to a sample (N = 217) of community-based women volunteers in
      Medellin, Colombia. Open-ended questions were included to assess the construct
      validity and cultural appropriateness of the LSC-R. The LSC-R was found to be
      valid and easily understood. Trauma exposure was common, but its assessment was
      not overly distressing to Colombian women.

PMID- 21728883
TI  - Health inequalities for women living in rural regions: the prefecture of Xanthi,
      Greece.
AB  - Gender equity with regard to access to health services has been set on a firm
      theoretical background but is far from reaching a resolution. Here we examine how
      geographic isolation affects the implementation of policies regarding equal
      access to health care by considering the case of the mountainous region of
      Xanthi, Greece. We determined that the characteristics of this mountainous region
      require additional measures to ensure truly equal access for women of all social
      and demographic groups. We also propose several interventions aimed at reducing
      health inequalities by involving the local population and broadening the target
      area.

PMID- 21728884
TI  - Slimming company websites in Hong Kong: implications for women's health.
AB  - This study sought to investigate, with a focus on the Hong Kong context, how
      commercial slimming websites portray the body image of beauty to the public, and
      to explore practical implications for related public health practices and health
      policy formulation. Commercial entities in the Hong Kong slimming industry were
      retrieved from the Hong Kong Yellow Page Directory and Yahoo Hong Kong Directory,
      and selected websites were coded and further analyzed. We found that
      irresponsible tactics are used in the slimming industry such that irresponsible
      messages prevail. Collaborative efforts from multidisciplinary sectors are needed
      to tackle the situation.

PMID- 21728885
TI  - The fibrosis of chronic pancreatitis: new insights into the role of pancreatic
      stellate cells.
AB  - SIGNIFICANCE: Prominent fibrosis is a major histological feature of chronic
      pancreatitis, a progressive necroinflammatory condition of the pancreas, most
      commonly associated with alcohol abuse. Patients with this disease often develop
      exocrine and endocrine insufficiency characterized by maldigestion and diabetes.
      Up until just over a decade ago, there was little understanding of the
      pathogenesis of pancreatic fibrosis in chronic pancreatitis. RECENT ADVANCES: In
      recent times, significant progress has been made in this area, mostly due to the
      identification, isolation, and characterization of the cells, namely pancreatic
      stellate cells (PSCs) that are now established as key players in pancreatic
      fibrogenesis. In health, PSCs maintain normal tissue architecture via regulation
      of the synthesis and degradation of extracellular matrix (ECM) proteins. During
      pancreatic injury, PSCs transform into an activated phenotype that secretes
      excessive amounts of the ECM proteins that comprise fibrous tissue. CRITICAL
      ISSUES: This Review summarizes current knowledge and critical aspects of PSC
      biology which have been increasingly well characterized over the past few years,
      particularly with respect to the response of PSCs to factors that stimulate or
      inhibit their activation and the intracellular signaling pathways governing these
      processes. Based on this knowledge, several therapeutic strategies have been
      examined in experimental models of pancreatic fibrosis, demonstrating that
      pancreatic fibrosis is a potentially reversible condition, at least in early
      stages. FUTURE DIRECTIONS: These will involve translation of the laboratory
      findings into effective clinical approaches to prevent/inhibit PSC activation so
      as to prevent, retard, or reverse the fibrotic process in pancreatitis.

PMID- 21728886
TI  - Vaginal gel drug delivery systems: understanding rheological characteristics and
      performance.
AB  - INTRODUCTION: Vaginal gels are used for a wide range of clinical and
      pharmaceutical applications. Gel performance in vivo, including spreading
      ability, retention and drug release behavior, is closely related to rheological
      properties. Hence, a comprehensive rheological characterization of candidate gel
      formulations is important in screening and designing appropriate vaginal gels to
      achieve optimal clinical performance. AREAS COVERED: In this review, the basic
      destructive (flow) and non-destructive (oscillation and creep) techniques,
      commonly used in the assessment of gels, are introduced. The main rheological
      properties discussed in this work include viscosity, storage modulus, loss
      modulus, loss tangent and strain growth under small stress loads. In particular,
      this paper reviews the rheological methods used in characterizing vaginal gels
      and discusses the factors that may influence rheological performance. Recent
      advances in rheological methods, the use of advanced rheological methods and the
      challenges facing formulation scientists are also reviewed. EXPERT OPINION: The
      complex and dynamic environment of the vagina requires a comprehensive
      understanding of the rheological performance of vaginal gels. The establishment
      of suitable rheological tests to appropriately define such characteristics may
      facilitate the selection of a gel that avoids leakage. The ideal gel platform
      must provide adequate coating with minimal leakage. This is extremely difficult
      to obtain as it requires the formulation of a gel with a suitable viscoelastic
      balance.

PMID- 21728887
TI  - Part set cuing in older adults: further evidence of intact forgetting in aging.
AB  - The aim of this study was to look at the effect of aging on part set cuing while
      equating for baseline performance in episodic memory. Younger and older
      participants listened to three different word lists, each containing 24 words
      relating to a particular category. During recall, 0, 33, or 66% of the items
      presented in the learning phase were re-presented as cues. The results showed
      that recall of the never cued items was equally impaired by the presence of cues
      in younger and older adults, thus showing equivalent part set cuing effects in
      both groups. These results parallel previous findings showing equivalent
      inhibitory effects in younger and older adults with tasks that do not require
      executive control and provide additional support to previous studies challenging
      the view that frontal/executive processes play a major role in part set cuing.

PMID- 21728888
TI  - Modeling recall memory for emotional objects in Alzheimer's disease.
AB  - OBJECTIVE: To examine whether emotional memory (EM) of objects with self
      reference in Alzheimer's disease (AD) can be modeled with binomial logistic
      regression in a free recall and an object recognition test to predict EM
      enhancement. METHOD: Twenty patients with AD and twenty healthy controls were
      studied. Six objects (three presented as gifts) were shown to each participant.
      Ten minutes later, a free recall and a recognition test were applied. The
      recognition test had target-objects mixed with six similar distracter objects.
      Participants were asked to name any object in the recall test and identify each
      object in the recognition test as known or unknown. RESULTS: The total of gift
      objects recalled in AD patients (41.6%) was larger than neutral objects (13.3%)
      and a significant EM recall effect for gifts was found (Wilcoxon: p < .003). EM
      was not found for recognition in AD patients due to a ceiling effect. Healthy
      older adults scored overall higher in recall and recognition but showed no EM
      enhancement due to a ceiling effect. A logistic regression showed that likelihood
      of emotional recall memory can be modeled as a function of MMSE score (p < .014)
      and object status (p < .0001) as gift or non-gift. CONCLUSION: Recall memory was
      enhanced in AD patients for emotional objects indicating that EM in mild to
      moderate AD although impaired can be provoked with strong emotional load. The
      logistic regression model suggests that EM declines with the progression of AD
      rather than disrupts and may be a useful tool for evaluating magnitude of
      emotional load.

PMID- 21728889
TI  - Training attentional control in older adults.
AB  - Recent research has demonstrated benefits for older adults from training
      attentional control using a variable priority strategy, but the construct
      validity of the training task and the degree to which benefits of training
      transfer to other contexts are unclear. The goal of this study was to
      characterize baseline performance on the training task in a sample of 105 healthy
      older adults and to test for transfer of training in a subset (n = 21). Training
      gains after 5 days and extent of transfer was compared to another subset (n = 20)
      that served as a control group. Baseline performance on the training task was
      characterized by a two-factor model of working memory and processing speed.
      Processing speed correlated with the training task. Training gains in speed and
      accuracy were reliable and robust (ps <.001, eta(2) = .57 to .90). Transfer to an
      analogous task was observed (ps <.05, eta(2) = .10 to .17). The beneficial effect
      of training did not translate to improved performance on related measures of
      processing speed. This study highlights the robust effect of training and
      transfer to a similar context using a variable priority training task. Although
      processing speed is an important aspect of the training task, training benefit is
      either related to an untested aspect of the training task or transfer of training
      is limited to the training context.

PMID- 21728890
TI  - The time course of access to semantic information in high-performing older
      adults: behavioral evidence for the hemispheric asymmetry reduction in OLDer
      individuals.
AB  - The possibility that the HAROLD phenomenon (i.e., Hemispheric Asymmetry Reduction
      in OLDer adults) is manifested in the course of access to semantic information,
      in particular the meaning of emotional words, was investigated using the visual
      half-field priming paradigm. The time course of priming was tracked in the
      cerebral hemispheres across three SOAs: 150, 300, and 750 ms. The results showed
      older and young adults had the same level of accuracy. While priming occurred
      unilaterally in young participants, the pattern of priming in older participants
      appeared to be bilateral whenever it was present, that is, at the 300- and 750-ms
      SOAs. The delay in the appearance of priming in older adults may be due to an
      increase in sensory thresholds that causes older adults to need more time to
      encode stimuli and fully activate their semantic network. It is concluded that
      the bilateral pattern of priming in the presence of an equivalent level of
      performance in older adults provides behavioral evidence supporting the
      compensatory role of the HAROLD phenomenon for this particular task.

PMID- 21728891
TI  - Goal orientation and self-efficacy in relation to memory in adulthood.
AB  - The achievement goal framework (Dweck, 1986, American Psychologist, 41, 1040) has
      been well-established in children and college-students, but has rarely been
      examined empirically with older adults. The current study, including younger and
      older adults, examined the effects of memory self-efficacy, learning goals
      (focusing on skill mastery over time) and performance goals (focusing on
      performance outcome evaluations) on memory performance. Questionnaires measured
      memory self-efficacy and general orientation toward learning and performance
      goals; free and cued recall was assessed in a subsequent telephone interview. As
      expected, age was negatively related and education was positively related to
      memory self-efficacy, and memory self-efficacy was positively related to memory,
      in a structural equation model. Age was also negatively related to memory
      performance. Results supported the positive impact of learning goals and the
      negative impact of performance goals on memory self-efficacy. There was no
      significant direct effect of learning or performance goals on memory performance;
      their impact occurred via their effect on memory self-efficacy. The present study
      supports past research suggesting that learning goals are beneficial, and
      performance goals are maladaptive, for self-efficacy and learning, and validates
      the achievement goal framework in a sample including older adults.

PMID- 21728892
TI  - Kinetic migration of isothiazolinone biocides from paper packaging to Tenax and
      Porapak.
AB  - Migration investigations were carried out on paper packaging materials in contact
      with solid food simulants. The aim was to investigate the migration behaviour of
      a series of isothiazolinone biocides (2-methyl-3-isothiazolinone (MI), 1,2
      benzisothiazolinone (BIT) and 2-octyl-3-isothiazolinone (OIT)) as potential
      contaminants in paper materials, at varying temperatures and migration times, for
      the food simulants Tenax and Porapak. Based on the migration results, Tenax was
      found to be a good food simulant, and was more suitable than Porapak at high
      temperature. Petri dishes were found to be suitable for use as migration cells
      when the compounds to be evaluated were non-volatile. The amount of migration
      gradually increased with time and increasing temperature, finally reaching a
      steady value. When the temperature was higher than the boiling point of OIT, the
      migration rate decreased because of volatilization. The maximum migration rates
      were 3.4% for MI, 2.2% for BIT and 10.6% for OIT at high temperature (>=100 
      degrees C). Two kinds of paper packaging for food were tested with the method
      that was developed. OIT in the papers migrated into the food simulants but the
      amount that migrated was less than 0.14 ug kg(-1).

PMID- 21728893
TI  - Free love: a case study of church-run home-based caregivers in a high
      vulnerability setting.
AB  - The purpose of this study is to explore the concept of religious health assets
      (RHA) and its relevance to HIV/AIDS. This manuscript describes the experiences of
      caregivers with a church-run home-based care organisation in Swaziland, site of
      the world's highest HIV prevalence (42%). In light of reduced antiretroviral
      treatment rollout in some areas of Africa, strengthening mechanisms of treatment
      support with HIV prevention has never been more critical. One modality may be
      community home-based care (CHBC), a core feature of the World Bank's Multi
      Country HIV/AIDS Program for Africa. Yet, these entities, and the frontline
      activities of local congregations, remain underexplored. Part of a larger
      anthropological study of religion and HIV/AIDS in Swaziland, this manuscript
      draws on 20 semi-structured caregiver interviews to discern patterns in
      motivations; perceived client needs; care practices; and meanings of religiosity.
      Thirteen participants were care coordinators who oversaw approximately 455
      caregivers across nearly half of the 22 communities served. Grounded theory
      analysis suggested that caregivers facilitated vital decisions around HIV
      testing, HIV disclosure, treatment uptake/adherence, as well as reduced HIV
      stigma. Also salient was the importance of a Christian ethos, in the form of
      'talk' and 'love', as critical culturally situated care practices. Having
      expanded to an estimated 600 caregivers and 2500 home-based clients between 2006
      and 2009, Participants' reports intimated their roles as agents of broader social
      transformation. This article contributes to the expanding study of RHA and
      challenges authoritative global public health strategies that have largely
      marginalised local religious aspects of HIV/AIDS. Future applied research
      examining how 'home' and 'church' may be vital public health settings outside of,
      but integral to, formal health services and HIV programming is warranted.

PMID- 21728894
TI  - Risk assessment of the lead intake by consumption of red deer and wild boar meat
      in Southern Spain.
AB  - The presence of heavy metals in big game meat may pose a risk to human health.
      The main objective of this paper is to carry out a risk assessment study (using a
      probabilistic and point-estimate approach) of lead intake by consumption of red
      deer and wild boar meat in Southern Spain based on Spanish data collected in the
      period 2003-2006. In general, the concentration levels found for wild boar meat
      (mean = 1291 ug kg(-1)) were much higher than those observed in red deer meat
      (mean = 326 ug kg(-1)). The results from a point-estimate risk assessment showed
      that the estimated average intake of lead among different exposure scenarios
      varied from 0.1 to 6.5 and from 0.3 to 38 ug kg(-1) week(-1) for red deer and
      wild boar meat, respectively; and from 0.3 to 35 ug kg(-1) week(-1) for
      individuals consuming both red deer and wild boar meat, and that the estimated
      intake of lead by consumption of big game meat differed significantly between
      hunters and non-hunters, it being higher for hunters. Besides this, results from
      the probabilistic risk assessment study corroborated the fact that risk is
      greater in hunter populations, reaching a maximum in individuals consuming only
      wild boar and both types of meat, with 0.4% and 0.2% of the population above the
      provisional tolerable weekly intake (PTWI), respectively. Likewise, the hunter
      populations consuming wild boar and both types of big game meat (red deer and
      wild boar meat) were exposed to the maximum lead level (56 ug kg(-1) week(-1)),
      which corresponded approximately to 224% of the PTWI. Further data and studies
      will be needed to give a complete risk estimation in which it will be crucial to
      consider the contribution to the lead intake level of other foods in the diet of
      both population groups.

PMID- 21728895
TI  - Average daily nitrate and nitrite intake in the Belgian population older than 15
      years.
AB  - The aim of this study was to assess the dietary intake of nitrate and nitrite in
      Belgium. The nitrate content of processed vegetables, cheeses and meat products
      was analysed. These data were completed by data from non-targeted official
      control and from the literature. In addition, the nitrite content of meat
      products was measured. Concentration data for nitrate and nitrite were linked to
      food consumption data of the Belgian Food Consumption Survey. This study included
      3245 respondents, aged 15 years and older. Food intakes were estimated by a
      repeated 24-h recall using EPIC-SOFT. Only respondents with two completed 24-h
      recalls (n=3083) were included in the analysis. For the intake assessment,
      average concentration data and individual consumption data were combined. Usual
      intake of nitrate/nitrite was calculated using the Nusser method. The mean usual
      daily intake of nitrate was 1.38 mg kg(-1) bodyweight (bw) day(-1) and the usual
      daily intake at the 97.5 percentile was 2.76 mg kg(-1) bw day(-1). Exposure of
      the Belgian population to nitrate at a mean intake corresponded to 38% of the ADI
      (while 76% at the 97.5 percentile). For the average consumer, half of the intake
      was derived from vegetables (especially lettuce) and 20% from water and water
      based drinks. The average daily intake of nitrate and nitrite from cheese and
      meat products was low (0.2% and 6% of the ADI at average intake, respectively).
      Scenario analyses with a higher consumption of vegetables or a higher nitrate
      concentration in tap water showed a significant higher intake of nitrate. Whether
      this is beneficial or harmful must be further assessed.

PMID- 21728898
TI  - Angiotensin II does not acutely regulate conduction velocity in rat atrial
      tissue.
AB  - AIM: Atrial angiotensin II (Ang II) levels are increased in atrial fibrillation
      and are believed to be important in the pathogenesis of atrial arrhythmias. Ang
      II reduces intercellular coupling by inhibiting gap junctions (connexins) and may
      thereby increase the risk of reentry arrhythmia. The aim of the current study was
      to investigate the acute effect of Ang II on conduction velocity (CV) in atrial
      tissue from normal and chronically infarcted rats. METHODS: Contractile force was
      measured and CV was determined from the conduction time between electrodes placed
      on the tissue preparation. Expression of AT1a and AT1b receptors was examined by
      real-time PCR. RESULTS: Acute stimulation with Ang II did not affect CV in tissue
      from auricle or atrial free wall. A transient 6.5 +/- 3.6% increase in resting
      tension was observed in atrial free wall preparations, indicating that receptors
      are present and functional in the free wall preparation. The difference between
      free wall and auricle was probably not caused by differences in receptor
      expression since equal amounts of AT1 mRNA were present. To test if myocardial
      infarction (MI) sensitizes the atrium to Ang II, free atrial wall from rats
      subjected to 4-5 weeks ventricular MI was examined. Although CV was significantly
      reduced by MI, no effect on CV of Ang II was seen. CONCLUSION: Ang II does not
      acutely regulate CV in tissue preparations from the free wall of the left atria
      or the left auricle. Although ventricular MI reduces CV, this does not sensitize
      the atria to Ang II.

PMID- 21728899
TI  - Influence of carbon monoxide leaks on the measurement error of total haemoglobin
      mass.
AB  - Total haemoglobin mass (Hb(mass)) can be assessed with low measurement error
      using carbon monoxide (CO) rebreathing. However, variability in measurement error
      of Hb(mass) has been reported across laboratories and it has previously been
      suggested that CO leaks contribute to this variability. As a result of employing
      a standardized leak monitoring procedure using two CO detectors, we were able to
      retrospectively examine the impact of CO leaks on Hb(mass) values from past test
      retest studies in our laboratory using the optimized CO rebreathing method. Test
      retest data were collected to determine measurement error, with subjects tested
      twice within 5 days. Test-retest data were placed into separate categories based
      on magnitude and duration of CO leak observed during one of the two tests. The No
      Leak category contained test-retest data in which no leak occurred during either
      test. The Minor Leak category contained test-retest data in which one of the
      tests had a CO leak of magnitude less than 30 ppm and less than 5 seconds
      duration, whereas the Major Leak category included test-retest data in which a
      leak greater than this magnitude or duration occurred. Measurement error was
      lowest in the No Leak category (1.9%; 95%CI: 1.6-2.3%; n = 56), approximately
      doubled in the Minor Leaks category (3.6%; 95%CI: 2.6-6.1%; n = 13), and
      dramatically increased in the Major Leaks category (9.3%; 95%CI: 6.3-17.6%; n =
      10). We recommend careful monitoring of potential CO leaks using multiple
      detectors. To minimize measurement error, tests in which any CO leak is detected
      should be excluded.

PMID- 21728900
TI  - Myocardial infarction induces early increased remote ADAM8 expression of rat
      hearts after cardiac arrest.
AB  - BACKGROUND: A disintegrin and metalloproteinase-8 (ADAM8) is a potential
      surrogate of inflammation which has recently been associated with myocardial
      infarction. We evaluated in a rat cardiac transplantation model whether ischemia
      reperfusion injury alone (IRI) or with early regional myocardial infarction (MI)
      would suffice to induce inflammatory myocardial remodeling and ADAM8 expression.
      MATERIAL AND METHODS: Isogenic heterotopic cardiac transplantation after cardiac
      arrest was performed to 48 Fischer 344 rats to induce ischemia-reperfusion injury
      (IRI), of which 27 rats also underwent ligation of the left anterior coronary
      artery (LAD) of the heart to yield MI. Histology was performed at 0.5, 24 and 48
      h after transplantation. ADAM8 was evaluated by qRT-PCR after graft harvesting.
      RESULTS: After 0.5 and 48 h respectively, edematous intramyocardial artery nuclei
      and periadventitial inflammation were more prominent in MI after transplantation,
      as compared with IRI alone and Controls (57.0 vs 40.0 and 5.0; 1.9 vs 1.1 and
      0.9, point score units, p < 0.05, respectively). The expression of ADAM-8 was
      increased in MI as compared with Controls (1.9 vs 1.0, 1.9 fold increase) at 48
      h. In grafts with MI, ADAM8 was localized using immunohistochemistry to the
      vicinity of the area corresponding to the developing infarction as well as in
      intramyocardial arteries remote to the infarction area. CONCLUSIONS: Remote
      histopathological changes of ischemic cardiac grafts are associated with
      increased expression of ADAM8 thus emphasizing a global myocardial impact of MI.

PMID- 21728901
TI  - Methylation status of the gene promoter of cyclin-dependent kinase inhibitor 2A
      (CDKN2A) in ovarian cancer.
AB  - OBJECTIVE: This study investigated the methylation status of the promoter of the
      tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A) in ovarian
      cancer. DESIGN AND METHODS: CDKN2A methylation was quantified by real-time PCR in
      ovarian biopsies of 52 patients with ovarian cancer, 43 patients with benign
      ovarian tumors and 40 patients with benign uterine pathology and healthy ovaries.
      RESULTS: CDKN2A methylation was detected in the three groups. The methylation
      level was higher in the cancer patients than in the other two groups (p = 0.0003)
      but was not different between benign tumors and healthy ovarian tissue (p >
      0.05). Using a cutoff threshold based on receiver-operating characteristic
      analysis, 21 patients with ovarian cancer and three patients with benign tumors
      were considered positive for CDKN2A methylation while all patients with healthy
      ovaries were considered negative. At the chosen cutoff, the diagnostic
      sensitivity was 40.4% and specificity 96.4%. CDKN2A methylation level and
      frequency were associated with high grade tumors (p = 0.0001 and p = 0.0005) but
      were not associated with disease stage or serum CA125 levels. However, it should
      be noted that most patients (92.3%) presented with advanced stage 3 or 4 disease.
      CONCLUSION: CDKN2A promoter methylation is common in ovarian cancer.
      Quantification of CDKN2A methylation may be useful in distinguishing malignant
      from benign ovarian tumors or healthy ovarian tissue.

PMID- 21728902
TI  - A disintegrin and metalloprotease -8 and -15 and susceptibility for ascending
      aortic dissection.
AB  - BACKGROUND. Dilatation of the ascending aorta (AA) is affected by extra-cellular
      matrix modifications and inflammation. A disintegrin and metalloproteases (ADAMs)
      may reveal differences between AA and ascending aortic dissection (AD). We
      characterized the inflammatory histology of AD and AA and examined the role of
      ADAM8 and -15 in these diseases. MATERIAL AND METHODS. Aortic wall histology and
      immunohistochemistry for leukocytes, T- and B-lymphocytes, plasma cells,
      macrophages, endothelial cells, smooth muscle cells, cell proliferation, elastase
      and Van-Gieson-staining were performed to 40 consecutive patients that underwent
      surgery for AA or AD. The expressions of ADAM8 and -15 mRNA and proteins were
      evaluated using QRT-PCR and immunohistochemistry. RESULTS. Thirty-four patients
      were enrolled, of which 29 had AA and five had AD of the ascending aorta. B-cells
      throughout the aortic wall and intimal plasma cells were more numerous during AD
      as compared with AA (p < 0.05). The gene expressions for ADAM8 and -15 were
      notably lower in AA as compared with AD. The median for down-regulation of ADAM8
      and -15 in AA was -2.7 and -1.8, respectively. ADAM8 and -15 were mainly found in
      the media layer in patients with AD. Two of the patients with AA and increased
      ADAMs developed AD of the remaining aorta. CONCLUSIONS. The involvement of ADAM8
      and -15 together with inflammation consisting of B-cells may indicate active
      remodelling of the aortic wall leading to AD.

PMID- 21728903
TI  - Valsartan plus hydrochlorothiazide: a review of its use since its introduction.
AB  - INTRODUCTION: This review focuses on the role of the fixed-dose combination (FDC)
      drug valsartan/hydrochlorothiazide (HCTZ) in the treatment of hypertension.
      Effective blood pressure control often is not achieved with monotherapy and,
      instead, requires combinations of drugs with different mechanisms of action to
      produce additive or synergistic effects. AREAS COVERED: FDC valsartan/HCTZ
      enhances not only efficacy for blood pressure control but also provides
      beneficial effects on target organs beyond that expected from arterial pressure
      reduction alone. Data describe key clinical trial experiences with the FDC, with
      particular attention to efficacy and tolerability. Literature searches of these
      various topics were conducted in January 2011. There is evidence of potential
      benefits with this combination associated with left ventricular hypertrophy, left
      ventricular dysfunction and renal disease. The FDC is an effective treatment for
      patients with hypertension and is superior to monotherapy than either drug alone.
      EXPERT OPINION: In addition to the benefits of each drug, valsartan/HCTZ's
      metabolic interactions reduce some of the negative effects of both compounds.
      With its increased simplicity, minimal side-effect profile and efficacy without a
      significant cost penalty, valsartan/HCTZ represents an excellent choice for
      antihypertensive therapy.

PMID- 21728904
TI  - The association between brain-derived neurotrophic factor Val66Met variants and
      psychotic symptoms in posttraumatic stress disorder.
AB  - OBJECTIVES: Psychotic symptoms frequently occur in veterans with combat-related
      posttraumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF)
      plays a major role in neurodevelopment, neuro-regeneration, neurotransmission,
      learning, regulation of mood and stress responses. The Met allele of the
      functional polymorphism, BDNF Val66Met, is associated with psychotic disorders.
      This study intended to assess whether the Met allele is overrepresented in
      unrelated Caucasian male veterans with psychotic PTSD compared to veteran
      controls. METHODS: The BDNF Val66Met variants were genotyped in 576 veterans: 206
      veterans without PTSD and 370 veterans with PTSD subdivided into groups with or
      without psychotic features. RESULTS: Veterans with psychotic PTSD were more
      frequently carriers of one or two Met alleles of the BDNF Val66Met polymorphism
      than veterans with PTSD without psychotic features and veterans without PTSD.
      CONCLUSIONS: The study shows that veterans with psychotic PTSD carried more Met
      alleles of the BDNF Val66Met than non-psychotic veterans with PTSD or veterans
      without PTSD. The results might add further support to the hypothesis that
      psychotic PTSD is a more severe subtype of PTSD.

PMID- 21728905
TI  - Fronto-temporal disconnectivity and symptom severity in children with autism
      spectrum disorder.
AB  - OBJECTIVES: There is increasing evidence that many of the core behavioural
      impairments in autism spectrum disorders (ASD) emerge from disconnectivity of
      networks that are important for social communication. The present study aimed at
      investigating which specific fibre tracts are impaired in ASD and if possible
      alterations of white matter are associated with clinical symptomatology. METHODS:
      Eighteen children with ASD and 18 carefully matched typically developing controls
      aged 6-12 years were examined using diffusion tensor imaging (DTI) and voxel
      based morphometry (VBM). Fractional anisotropy (FA) values were correlated with
      symptom severity as indexed by the children's scores on the Autisms Diagnostic
      Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R).
      RESULTS: Decreased FA values were identified for the fornix (FO), the superior
      longitudinal fasciculus (SLF) the corpus callosum and the uncinate fasciculus
      (UF) in the ASD group compared to controls, with most prominent differences in
      the UF bilaterally and the right SLF. FA values of affected fibre tracts were
      negatively associated with clinical measures of autistic symptomatology. We did
      not observe significantly altered grey or white matter concentration after
      correction for multiple comparisons. CONCLUSION: Our findings support the
      hypothesis of abnormal white matter microstructure of fronto-temporal cortical
      networks in ASD, which are associated with core symptoms of the disorder.

PMID- 21728906
TI  - Emotion processing facilitates working memory performance.
AB  - The effect of emotional stimulus content on working memory performance has been
      investigated with conflicting results, as both emotion-dependent facilitation and
      impairments are reported in the literature. To clarify this issue, 52 adult
      participants performed a modified visual 2-back task with highly arousing
      positive stimuli (sexual scenes), highly arousing negative stimuli (violent
      death) and low-arousal neutral stimuli. Emotional stimulus processing was found
      to facilitate task performance relative to that of neutral stimuli, both in
      regards to response accuracy and reaction times. No emotion-dependent differences
      in false-alarm rates were found. These results indicate that emotional
      information can have a facilitating effect on working memory maintenance and
      processing of information.

PMID- 21728907
TI  - Vitamin D deficiency, myositis-myalgia, and reversible statin intolerance.
AB  - OBJECTIVE: In 150 hypercholesterolemic patients, unable to tolerate >=1 statin
      because of myositis-myalgia, selected by low (<32 ng/ml) serum 25 (OH) vitamin D,
      we prospectively assessed whether vitamin D supplementation with resolution of
      vitamin D deficiency would result in statin tolerance, free of myositis-myalgia.
      RESEARCH DESIGN AND METHODS: We studied 74 men, 76 women, median age 60, 131
      white, 17 black and 2 other. On no statins, 50,000 units of vitamin D was given
      twice a week for 3 weeks, and then continued once a week. After 3 weeks on
      vitamin D, statins were restarted. Patients were re-assessed on statins and
      vitamin D every 3 to 4 months, with serial measures of serum 25 (OH) vitamin D,
      creatine phosphokinase (CPK), LDL cholesterol (LDLC) and assessment of myositis
      myalgia. MAIN OUTCOME MEASURES: Percentage of patients myalgia-free on vitamin D
      plus reinstituted statins, serum 25 (OH) vitamin D, CPK, and LDLC on reinstituted
      statins and concurrent vitamin D supplementation. RESULTS: On vitamin D
      supplementation plus re-instituted statins for a median of 8.1 months, 131 of the
      150 patients (87%) were free of myositis-myalgia and tolerated the statins well.
      Serum 25 (OH) vitamin D increased from median 21 to 40 ng/ml (p < 0.001), and
      normalized (>=32 ng/ml) in 117 (78%) of 150 previously vitamin D deficient,
      statin-intolerant patients. Median LDLC decreased from 146 mg/dl to 95 mg/dl, p <
      0.001. CONCLUSION: Symptomatic myositis-myalgia in hypercholesterolemic statin
      treated patients with concurrent serum 25 (OH) vitamin D deficiency may reflect a
      reversible interaction between vitamin D deficiency and statins on skeletal
      muscle causing myalgia.

PMID- 21728908
TI  - Mechanical ventilation during anaesthesia: challenges and opportunities for
      investigating the respiration-related cardiovascular oscillations.
AB  - The vast majority of the available literature regarding cardiovascular
      oscillations refers to spontaneously breathing subjects. Only a few studies
      investigated cardiovascular oscillations, and especially respiration-related ones
      (RCVO), during intermittent positive pressure mechanical ventilation (IPPV) under
      anaesthesia. Only a handful considered assisted IPPV, in which spontaneous
      breathing activity is supported, rather than replaced as in controlled IPPV. In
      this paper, we review the current understanding of RCVO physiology during IPPV,
      from literature retrieved through PubMed website. In particular, we describe how
      during controlled IPPV under anaesthesia respiratory sinus arrhythmia appears to
      be generated by non-neural mechano-electric feedback in the heart (indirectly
      influenced by tonic sympathetic regulation of vascular tone and heart
      contractility) and not by phasic vagal modulation of central origin and/or
      baroreflex mechanisms. Furthermore, assisted IPPV differs from controlled IPPV in
      terms of RCVO, reintroducing significant central respiratory vagal modulation of
      respiratory sinus arrhythmia. This evidence indicates against applying to IPPV
      interpretative paradigms of RCVO derived from spontaneously breathing subjects,
      and against considering together IPPV and spontaneously breathing subjects for
      RCVO-based risk assessment. Finally, we highlight the opportunities that IPPV
      offers for future investigations of RCVO genesis and interactions, and we
      indicate several possibilities for clinical applications of RCVO during IPPV.

PMID- 21728909
TI  - A new electronic device for subcutaneous injection of IFN-beta-1a.
AB  - Disease-modifying drugs (DMDs) can provide important benefits for patients with
      multiple sclerosis (MS), but nonadherence to treatment is associated with an
      increased risk of relapse. All first-line DMDs used in MS require regular
      injection, but injection-related problems are common barriers to treatment
      adherence. Autoinjectors that allow automatic injection at the press of a button
      have increased the ease and convenience of injection, compared with manual
      injection. A new electronic autoinjector has recently been introduced for the
      administration of subcutaneous IFN-beta-1a. This device is the first electronic
      autoinjector for use with any MS therapy, and includes several innovative
      features that may be advantageous to patients. One of these features is an
      accurate electronic dosing log, which can be viewed by the patient and the
      healthcare provider. This article discusses this new electronic device in the
      context of other autoinjectors currently used to self-inject first-line DMDs in
      MS.

PMID- 21728910
TI  - Chronic noncancer pain intensity is inversely related to analgesic adherence in
      pain clinics.
AB  - OBJECTIVE: The relationship between chronic noncancer pain (CNCP) control and
      pain medication (analgesic) adherence has not been widely documented. The primary
      aim of this study was to evaluate the relationship between pain intensity and the
      degree of adherence to analgesic medication prescribed in pain clinics. There was
      also a special emphasis on the influence of polypharmacy on adherence. METHODS: A
      cross-sectional clinical survey was carried out in pain clinics across Spain.
      Demographic and clinical data were collected from patients: pain intensity,
      analgesic prescription and adherence, and the presence of concomitant medical
      conditions and treatments. The relationship between analgesic adherence and pain
      intensity was analyzed using correlations and propensity scores based on ordinal
      logistic regression. Correlates of pain intensity were explored using multiple
      linear regression. RESULTS: Data was gathered from 1407 patients; 1321 were
      eligible for analysis. Their mean (standard deviation) age was 61.6 (14.7) years
      and the majority (67.3%) were women. More than half (57.9%) received step 3
      analgesics. Pain intensity was scored 5 out of 10 on average. Just 65.9% of
      patients were reported to not have missed any analgesic dose during the previous
      week. Pain intensity correlated negatively with analgesic adherence (r(s) = 
      0.151, p < 0.001). Moderate versus very intense pain was predicted in patients
      with 'good' and 'very poor' adherence, respectively. The presence of concomitant
      medications also correlated negatively with analgesic adherence (r(s) = -0.074, p
      = 0.007). However, few investigators reported such a negative effect of
      polypharmacy. LIMITATIONS: Key limitations of this research are its cross
      sectional design and the absence of an objective means of measuring medication
      adherence. CONCLUSIONS: This study has shown that there is a small but
      significant inverse relationship between analgesic adherence and CNCP control,
      which has remained elusive to date and should be further evaluated. Polypharmacy
      also had a negative influence on adherence, although this was not acknowledged by
      all investigators.

PMID- 21728911
TI  - A cost-effectiveness analysis of levodopa/carbidopa intestinal gel compared to
      standard care in late stage Parkinson's disease in the UK.
AB  - OBJECTIVE: Evaluation of cost-effectiveness of levodopa/carbidopa intestinal gel
      (LCIG), compared to standard care (SC) in patients with advanced Parkinson's
      disease (aPD) in the UK. DESIGN: Markov model to quantify costs and outcomes
      associated with LCIG versus SC in aPD patients at Hoehn and Yahr (H&Y) stages 3,
      4 or 5 experiencing >50% OFF time per day. Time horizon was lifetime, LCIG
      treatment was assumed to last maximal 5 years after which patients revert to SC.
      Model comprised 12 aPD health states according to H&Y status and daily time spent
      in OFF state. Cost analyses are reported from a UK NHS and Personal Social
      Services perspective. Uncertainties were assessed through one-way sensitivity
      analyses. COMPARATORS: LCIG, providing patients with continuous dopaminergic
      stimulation to maximise functional ON time during the day and SC, defined as
      medically determined best available oral medication. MAIN OUTCOME MEASURES: Cost
      effectiveness, based on quality adjusted life years gained, presented as an
      incremental cost-effectiveness ratio. RESULTS: Lifetime analysis yields an
      incremental cost per QALY of L36,024 for LCIG compared to SC (incremental cost
      L39,644, QALY gain 1.1). Results were sensitive to time on treatment, health
      state on treatment initiation, and estimates of long term benefit (OWSA results
      from L32,127 to L66,421 per QALY). Findings must be considered in the context of
      the study limitations which were mainly due to data availability constraints.
      CONCLUSIONS: LCIG is an effective treatment, reducing OFF time and improving
      quality of life in advanced PD. It provides value for money in levodopa
      responsive aPD patients with severe motor fluctuations when no other treatment
      options are effective or suitable. Given LCIG is an orphan drug, it is reasonable
      to suggest that it may be considered cost-effective in the UK setting. However,
      further research is needed to complete current data gaps and increase robustness
      of the model.

PMID- 21728912
TI  - Healthcare costs associated with bevacizumab and cetuximab in second-line
      treatment of metastatic colorectal cancer.
AB  - OBJECTIVE: To compare the health care costs of patients with metastatic
      colorectal cancer (mCRC) who received second-line treatment with Avastin
      (bevacizumab) versus Erbitux (cetuximab), from the third-party payer's
      perspective. METHODS: Patients with mCRC were selected from the PharMetrics
      claims database if they received second-line therapy containing either
      bevacizumab (second-line bevacizumab cohort) or cetuximab (second-line cetuximab
      cohort). Six-month costs following second-line therapy start date and average
      monthly healthcare costs while on second-line therapy (in 2009 US$) were
      calculated and compared between the two groups. RESULTS: A total of 2188 patients
      with mCRC who met the eligibility criteria were included in the analysis,
      including 1808 patients receiving bevacizumab and 380 patients receiving
      cetuximab in second-line treatment. Demographic and baseline characteristics were
      similar between the two groups. Patients' mean age was 61 years and 56% were
      males. In second-line treatment, bevacizumab was commonly used with oxaliplatin
      (43.5%) and irinotecan-based regimens (40.4%), whereas cetuximab was commonly
      used with irinotecan-based regimens (68.2%). Bevacizumab patients had
      significantly lower total all-cause healthcare costs than cetuximab patients
      (adjusted difference: -$10,231, p = 0.020), and lower medical costs (-$10,796, p
      = 0.012) during the 6 months following second-line therapy initiation.
      Approximately half of the difference in total all-cause healthcare costs was
      attributable to the lower chemotherapy and targeted therapy costs (-$5635, p =
      0.032) of bevacizumab patients than those of cetuximab patients. While on second
      line therapy, bevacizumab patients also had lower average monthly all-cause
      healthcare costs than cetuximab patients. LIMITATIONS: Second-line treatment in
      the current study was defined based on changes in mCRC medications, not based on
      disease progression due to the limited clinical information available in claims.
      CONCLUSION: The use of bevacizumab in second-line therapy was associated with
      significantly lower healthcare costs in mCRC patients, compared to the use of
      cetuximab.

PMID- 21728913
TI  - Mail-order pharmacy use and medication adherence among Medicare Part D
      beneficiaries with diabetes.
AB  - OBJECTIVE: To examine medication adherence among Medicare Part D beneficiaries
      initiating oral anti-diabetic medications and explore whether there is any
      association of using mail-order pharmacy (vs. retail pharmacy) with better
      adherence in this patient population. RESEARCH DESIGN AND METHODS: Using
      administrative pharmacy claims data, we conducted a retrospective cohort study on
      Medicare Part D beneficiaries who newly initiated oral anti-diabetic treatment
      between July 1, 2008 and December 31, 2008. Mail-order pharmacy users were
      matched to retail pharmacy users via propensity scoring, controlling for patient
      demographic and clinical characteristics. Adherence with oral anti-diabetic
      medications during the benefit year of 2009 was assessed using the proportion of
      days covered (PDC). Comparison of medication adherence between the mail-order
      pharmacy group and retail pharmacy group was conducted in the propensity matched
      sample using the paired t-tests and McNemar's tests. RESULTS: A total of 22,546
      patients who initiated oral anti-diabetic medications were identified. The
      average PDC was 0.60 and only 41.6% of the study population attained good
      adherence (defined as PDC >= 0.8) with oral anti-diabetic medications during
      calendar year 2009. The matched sample included 1361 patients in each of the mail
      order and retail pharmacy cohorts. Compared with the retail pharmacy group, mail
      order pharmacy users demonstrated a significantly higher PDC (0.68 vs. 0.61; P <
      0.001) throughout the benefit year. More patients in the mail-order pharmacy
      group (49.7%) attained good adherence with their oral anti-diabetic medications
      compared to 42.8% in the retail pharmacy group (P < 0.001). LIMITATIONS: The
      study was subject to limitations inherent in retrospective claims database
      analysis. CONCLUSIONS: Adherence with oral anti-diabetic medications among
      Medicare Part D beneficiaries is suboptimal. Patients using mail-order pharmacy
      had better adherence to oral anti-diabetic medications than those who used retail
      pharmacies. However, the causal relationship between mail-order pharmacy use and
      adherence should be further examined in a randomized study setting.

PMID- 21728914
TI  - Comparison of real-world adherence, healthcare resource utilization and costs for
      newly initiated valsartan/amlodipine single-pill combination versus angiotensin
      receptor blocker/calcium channel blocker free-combination therapy.
AB  - OBJECTIVE: To compare adherence, healthcare costs and utilization of
      valsartan/amlodipine single-pill combination (SPC) and angiotensin-receptor
      blocker/calcium-channel blocker multiple-pill free-combination (ARB + CCB FC)
      therapy using real-world data. METHODS: A retrospective study (January 1, 2007 to
      April 30, 2009) was conducted using US commercial healthcare insurance claims.
      Patients were assigned to two cohorts: 'valsartan/amlodipine SPC cohort' and 'ARB
      + CCB FC therapy cohort'. The primary endpoints were adherence and persistence.
      The secondary endpoints were 1-year healthcare costs and utilization. RESULTS:
      Out of 12,628 eligible patients 3259 (26%) were included in the
      valsartan/amlodipine SPC cohort and 9369 (%74) in the ARB + CCB FC cohort. Risk
      adjusted adherence rates were higher for valsartan/amlodipine SPC patients [OR:
      1.38, 95% CI: (1.24, 1.53)]. The Cox proportional hazard model showed that
      valsartan/amlodipine SPC cohort patients were less likely to discontinue
      medication (HR: 0.87, p < 0.001). Comparison between the groups also yielded that
      total healthcare costs of valsartan/amlodipine SPC patients were 16-20% lower
      than ARB + CCB FC therapy patients (p < 0.0001). LIMITATIONS: Since claims data
      are collected for payment purposes rather than research purposes, the study is
      bound by limitations for the retrospective analysis. For example, the presence of
      a claim for a filled prescription does not indicate that the medication was
      consumed or taken as prescribed. Data on health behaviors and patient lifestyle
      were not available. Over-the-counter medications and clinical disease severity
      were not available in the dataset. Incorrect coding is also a possibility.
      However, we have used previously validated datasets where these effects are
      minimal. Heterogeneity of the sample may create bias in our estimates, however,
      we have used advanced statistical methods to control for observed and unobserved
      bias. CONCLUSION: The real-world use of valsartan/amlodipine SPC was associated
      with better adherence and persistence relative to ARB + CCB FC therapy among
      patients with hypertension. Moreover, patients taking single-pill combination
      therapy had lower healthcare costs and utilization.

PMID- 21728915
TI  - Fetal outcome for infants in breech by method of delivery: experiences with a
      stand-by service system of senior obstetricians and women's choices of mode of
      delivery.
AB  - OBJECTIVE: To show that the fetal outcome in vaginal deliveries (VD) of breech
      presentation in a setting of a senior obstetrician stand-by system is as good as
      in planned cesarean sections. PATIENTS AND METHODS: This observational
      prospective intent-to-treat study (n=211 singleton breech presentation
      pregnancies of >=35 weeks of gestation) compared two groups of breech deliveries:
      planned cesarean sections (PCS, n=126) and intended VD (IVD, n=85) resulting in
      vaginal deliveries (VD, n=46) as well as secondary cesarean sections (SCS, n=39).
      Women's informed choice as well as strict pre-selection criteria for vaginally
      intended breech presentation deliveries was followed. RESULTS: Fetal outcome of
      vaginal breech deliveries and of primary as well as SCS (45.9% of IVD) was
      comparable in terms of cord blood pH, base excess, Apgar score, fetal trauma, and
      transfer to neonatal intensive care unit. CONCLUSIONS: Vaginal breech delivery is
      a safe option in a stand-by system of senior obstetricians with controlled
      decision-making before labor.

PMID- 21728916
TI  - Gestational diabetes mellitus complicating twin pregnancies.
AB  - OBJECTIVE: To compare outcomes of twin pregnancies with and without gestational
      diabetes mellitus (GDM). STUDY DESIGN: We compared 105 twin pregnancies with GDM
      (7.8% of all twin pregnancies) to 315 controls without GDM, matched for
      gestational age, chorionicity and year of birth. RESULTS: Pre-gravid obesity
      appears to predispose women to GDM during twin pregnancy [odds ratio (OR) 3.5;
      95% confidence interval (CI) 1.7, 7.0]. Overweight and obese women that
      subsequently developed GDM during their twin gestation were less likely to
      conceive spontaneously (OR 0.4; 95% CI 0.3, 0.7). Twins from the GDM group had
      more respiratory distress syndrome (RDS, OR 2.2; 95% CI 1.3, 3.7) and had a three
      fold, but not significantly increased perinatal mortality rate. Birth weight
      characteristics were similar in both groups. CONCLUSION: Twin pregnancies
      complicated by GDM might be associated with pre-pregnancy maternal obesity and
      are at increased risk of RDS and non-significant increased risk of perinatal
      death.

PMID- 21728917
TI  - Supracervical cerclage with intracavitary balloon to control bleeding associated
      with placenta previa.
AB  - OBJECTIVE: A supracervical cerclage suturing technique with an intracavitary
      balloon (SCCB) was developed to simultaneously compress bleeding from the
      placental bed and the outside uterine wall. STUDY DESIGN: Twenty cesarean
      sections were performed due to placenta previa over three years. The SCCB was
      used in 13 patients with uncontrolled bleeding after failure of conventional
      methods. The conventional surgical hemostatic techniques were applied first in
      patients with copious bleeding due to placenta previa. If bleeding continued, a
      three-way Foley catheter was inserted into the uterine cavity through the cervix
      and SCCB was performed. About 50-100 mL of normal saline was infused to inflate
      the catheter balloon. On the next morning, attempts were made to withdraw the F
      catheter but if bleeding started again, another 12 h of pressure was provided.
      RESULTS: The mean removal time for the intracavitary Foley catheter was 20.6+/
      12.3 h. There was one case of subtotal hysterectomy after the SCCB. All patients
      were followed for at least 12 months. There were no specific complications
      related to the procedure. All women returned to their normal menstrual cycles and
      one had an ongoing third trimester pregnancy. CONCLUSION: The SCCB is a simple
      and effective technique to control bleeding associated with placenta previa.

PMID- 21728920
TI  - Snack bars with high soy protein and isoflavone content for use in diets to
      control dyslipidaemia.
AB  - The objective was to develop a cereal bar product rich in isoflavones and soy
      protein to be used in diets for controlling dyslipidaemia. A soy snack bar with
      39.88 g/100 g dietary fibre, 34.25 g/100 g protein, 100.39 mg/100 g isoflavones
      and 245.47 kcal/100 g was produced. The shelf life of the product was tested over
      a period of 6 months. The hardness, water activity and darkness of the snack bars
      increased with storage time. Clinical trial was carried out to evaluate the
      effectiveness of the soy snack bar on the lipid profiles of 22 dyslipidaemic
      subjects for a period of 45 days. There was a decrease in levels of triglycerides
      (TGs) (- 20%) and an increase in high-density lipoprotein cholesterol (HDL-c)
      (+8%) comparing with baseline values. Therefore, relatively high intakes of soy
      protein and isoflavones in moderately hypercholesterolaemic subjects (>200 mg/dl)
      may have a moderately beneficial effect on plasma lipid profiles, as TG and HDL-c
      levels, without additional diet restrictions.

PMID- 21728924
TI  - Measures of self-care independence for children with osteochondrodysplasia: a
      clinimetric review.
AB  - This systematic review evaluates the validity, reliability, and clinical utility
      of outcome measures used to assess self-care skills among children with
      congenital musculoskeletal conditions and assesses the applicability of these
      measures for children with osteochondrodysplasia aged 0-12 years. Electronic
      databases were searched to identify self-care assessments that addressed the self
      care domain as defined by of the International Classification of Function
      Disability and included children with osteochondrodysplasia. Ten measures were
      identified and three met the inclusion criteria: the Functional Independence
      Measure for Children (WeeFIM), the Activities Scale for Kids (ASK), and the
      Pediatric Evaluation of Disability Inventory (PEDI). Although psychometric data
      specific to children with osteochondrodysplasia are limited, adequate to
      excellent reliability and evidence of validity were reported for all three
      instruments for children with physical disabilities. Further evaluation of
      psychometric properties of self-care instruments specifically for children with
      osteochondrodysplasia would be beneficial to help identify instruments that will
      assist with improved assessment and management.

PMID- 21728925
TI  - Occupational therapy practitioners' perceptions of important competencies for
      handwriting evaluation and intervention in school-aged children.
AB  - OBJECTIVE: The primary purpose of this study was to identify the practitioner
      competencies that occupational therapists perceive as important for handwriting
      evaluation and intervention in school-aged children. A secondary purpose was to
      compare the practitioner perceptions of those in school-based practice with those
      from other primary practice settings. METHOD: A stratified random sample of 376
      occupational therapists recruited from a national professional organization
      database participated by completing a survey instrument containing 80 competency
      items. RESULTS: A majority of the 80 practitioner competency items were perceived
      to be of high importance to the respondent groups. A significance difference in
      perception when comparing the school-based practitioners to all other
      practitioners was revealed in only 3-12 competency summary categories.
      CONCLUSION: Practitioner competency survey items were perceived to be of high
      importance to the participants. School-based practitioner perceptions of
      competency were, for the most part, mainly similar to those in other primary
      practice settings.

PMID- 21728926
TI  - The Drug Metabolism Discussion Group in 2011.

PMID- 21728927
TI  - Oral ulcers and necrotizing gingivitis in relation to HIV-associated neutropenia:
      a review and an illustrative case.
AB  - An unusual case of necrotizing gingivitis and neutropenic oral ulcers in an HIV
      seropositive patient is presented. In spite of a very low CD4(+) T cell count and
      severe neutropenia, the necrotizing gingivitis responded favorably to standard
      periodontal treatment, and the oral ulcers healed after administration of
      granulocyte colony-stimulating factor (G-CSF). Nonspecific oral ulcers in HIV
      seropositive subjects with neutropenia should be regarded as neutropenic ulcers.
      The term nonspecific ulcers should be restricted to those ulcers with nonspecific
      histopathological features in patients without neutropenia or a nutritional
      deficiency such as iron, folic acid, and vitamin B.

PMID- 21728928
TI  - Nanosilica? Clarifications are necessary!

PMID- 21728930
TI  - A no-fault compensation scheme for serious adverse events attributed to
      vaccination.

PMID- 21728931
TI  - Food allergy: is there a rising prevalence and if so why?

PMID- 21728932
TI  - Is Australia ready to use glycated haemoglobin for the diagnosis of diabetes?

PMID- 21728933
TI  - The rationale for pregnancy registers for women with epilepsy.

PMID- 21728934
TI  - Socioeconomic disparities in stroke rates and outcome: pooled analysis of stroke
      incidence studies in Australia and New Zealand.
AB  - OBJECTIVE: To assess the influence of area-level socioeconomic status (SES) on
      incidence and case-fatality rates for stroke. DESIGN, SETTING AND PARTICIPANTS:
      Analysis of pooled data for 3077 patients with incident stroke from three
      population-based studies in Perth, Melbourne, and Auckland between 1995 and 2003.
      MAIN OUTCOME MEASURES: Incidence and 12-month case-fatality rates for stroke.
      RESULTS: Annual age-standardised stroke incidence rates ranged from 77 per
      100,000 person-years (95% CI, 72-83) in the least deprived areas to 131 per
      100,000 person-years (95% CI, 120-141) in the most deprived areas (rate ratio,
      1.70; 95% CI, 1.47-1.95; P < 0.001). The population attributable risk of stroke
      was 19% (95% CI, 12%-27%) for those living in the most deprived areas compared
      with the least deprived areas. Compared with people in the least deprived areas,
      those in the most deprived areas tended to be younger (mean age, 68 v 77 years; P
      < 0.001), had more comorbidities such as hypertension (58% v 51%; P < 0.001) and
      diabetes (22% v 12%; P < 0.001), and were more likely to smoke (23% v 8%; P <
      0.001). After adjustment for age, area-level SES was not associated with 12-month
      case-fatality rate. CONCLUSIONS: Our analysis provides evidence that people
      living in areas that are relatively more deprived in socioeconomic terms
      experience higher rates of stroke. This may be explained by a higher prevalence
      of risk factors among these populations, such as hypertension, diabetes and
      cigarette smoking. Effective preventive measures in the more deprived areas of
      the community could substantially reduce rates of stroke.

PMID- 21728935
TI  - Stroke and transient ischaemic attack awareness.
AB  - OBJECTIVE: This study examined the knowledge of stroke warning signs and risk
      factors among the general public, including what they would do if they were to
      develop such symptoms. DESIGN, SETTING AND PARTICIPANTS: Population study of
      randomly selected members of the general public in Adelaide, South Australia. A
      simple survey assessed knowledge of stroke warning signs and gave four options
      for management. The survey was conducted on three separate occasions: before,
      immediately after and 3 months after the National Stroke Foundation's National
      Stroke Week in 2009. MAIN OUTCOME MEASURES: The outcome measures were the public
      perception of risk factors and warning signs of stroke and what the members of
      the public would do if presented with a range of warning signs. They were also
      asked about their knowledge of the Face, Arms, Speech, Time (FAST) test. RESULTS:
      The three surveys were completed by 251 members of the public. Hypertension and
      smoking were recognised as risk factors for stroke by 71% and 53% of respondents
      respectively. Before National Stroke Week, slurred speech was identified by 51%
      and both slurred speech and upper limb sensory loss was identified by 62% as
      warning signs to provoke presentation to an emergency department (ED). Amaurosis,
      upper limb sensory loss, upper limb numbness and upper limb weakness were
      correctly identified individually as warning signs to attend an ED by fewer than
      one-third of respondents. There was no significant difference in the survey
      results following National Stroke Week. CONCLUSIONS: Public awareness of the
      symptoms of stroke, and what to do about them, is limited. There was little
      improvement after the national week-long awareness campaign. The lack of public
      awareness about stroke warning signs must be addressed to reduce mortality and
      morbidity from stroke.

PMID- 21728936
TI  - Advertising of fast food to children on Australian television: the impact of
      industry self-regulation.
AB  - OBJECTIVE: To assess the impact of the quick-service restaurant industry (QSRI)
      self-regulatory initiative on fast-food advertising to children on Australian
      commercial television. DESIGN AND SETTING: Analysis of advertisements for foods
      on the three main free-to-air commercial television channels (channels 7, 9 and
      10) in Sydney, Australia, over 4 days in both May 2009 and April 2010 in terms
      of: number of advertisements; types of food (coded core [healthy] foods, non-core
      [unhealthy] foods, miscellaneous foods; or fast foods); whether advertised meals
      were intended for children; whether advertisements were broadcast during
      children's peak viewing times; and whether the company in question was a
      signatory to the QSRI initiative. MAIN OUTCOME MEASURES: Change in the mean
      frequency and rate of food advertisements per hour from 2009 to 2010; change in
      the types of fast-food meals (healthier alternatives [at least one nutrient
      dense, low-energy food considered part of a healthy diet for children], non-core
      [high in undesirable nutrients and not considered part of a healthy diet for
      children], and other) being advertised; and proportion of children's energy
      requirements provided by fast-food meals. RESULTS: From 2009 to 2010, the mean
      frequency of fast-food advertisements increased from 1.1 to 1.5 per hour. While
      non-core fast foods comprised a lesser share of fast-food advertising in 2010
      than 2009, the mean frequency at which they were advertised during times when the
      largest numbers of children were watching television remained the same (1.3 per
      hour in both 2009 and 2010). Family meals advertised for children's consumption
      in 2010 provided energy far in excess of children's requirements. CONCLUSIONS:
      Children's exposure to unhealthy fast-food advertising has not changed following
      the introduction of self-regulation, and some fast foods advertised for
      children's consumption contain excessive energy. The limited impact of self
      regulation suggests that governments should define the policy framework for
      regulating fast-food advertising to children.

PMID- 21728937
TI  - Prevalence and characteristics of complaint-prone doctors in private practice in
      Victoria.
AB  - OBJECTIVE: To identify characteristics of doctors who are repeated subjects of
      complaints by patients. DESIGN AND SETTING: Case-control study of doctors about
      whom patients had complained to the Victorian Health Services Commissioner
      between 1 January 2000 and 31 December 2009. PARTICIPANTS: 384 doctors in private
      practice; cases comprised 96 doctors who were the subject of four or more
      separate complaints; and the control group comprised 288 doctors who were the
      subject of a single complaint over the study period. RESULTS: Among doctors in
      private practice in Victoria, 20.5% (95% CI, 19.7%-21.3%) experienced at least
      one complaint over the decade. Among doctors who were the subject of a complaint,
      4.5% (95% CI, 3.6%-5.4%) had four or more complaints, and this group accounted
      for 17.6% (95% CI, 16.3%-19.0%) of all complaints to the Victorian Health
      Services Commissioner. Multivariate analyses showed that surgeons (odds ratio
      [OR], 8.90; 95% CI, 3.69-21.50) and psychiatrists (OR, 4.59; 95% CI, 1.46-14.43)
      had higher odds of being in the complaint-prone group than general practitioners.
      Doctors trained overseas had lower odds of being complaint-prone than those
      trained in Australia (OR, 0.31; 95% CI, 0.13-0.72). CONCLUSIONS: A small group of
      doctors in private practice in Victoria account for nearly 18% of complaints.
      Interventions to improve patient satisfaction and public confidence in health
      services should target complaint-prone subgroups of practitioners.

PMID- 21728938
TI  - Clinical practice guidelines: the need for greater transparency in formulating
      recommendations.
AB  - A recently published critique of a set of Australian clinical practice guidelines
      (CPG) highlighted problematic issues in guideline development concerning
      conflicts of interest of guideline panellists, validity and strength of
      recommendations, and involvement of end users and external stakeholders.
      Management of financial or intellectual conflicts of interest requires: full
      disclosure; limitations on industry or agency financial support during guideline
      development; a representative panel that includes conflict-free members; and only
      conflict-free panellists to be involved in drafting guideline recommendations.
      Guideline panels should consider adopting the GRADE (Grading of Recommendations
      Assessment, Development and Evaluation) system to assist in determining the
      validity and strength of recommendations. Guideline panels should seek formal
      feedback from external stakeholders and end users. Enacting such policies aims to
      lend greater transparency and credibility to CPG, limit protracted and unhelpful
      interpretive debates, and promote wider use of CPG.

PMID- 21728939
TI  - A practical approach to the management of lower urinary tract symptoms among men.
AB  - Lower urinary tract symptoms (LUTS) are common among Australian men over the age
      of 45 years; most men with LUTS will have benign prostatic hyperplasia (BPH),
      overactive bladder (OAB), or both. The cause of LUTS should be diagnosed by
      assessing symptom severity and excluding of medical or pharmaceutical causes. All
      men with LUTS should undergo digital rectal examination; other diagnostic tools
      include urine and blood testing, voiding charts and imaging. Depending on disease
      severity, impact on quality of life, patient preference, presence of
      complications and fitness for surgery, BPH is managed with watchful waiting,
      pharmacotherapy (alpha-blockers or 5-alpha-reductase inhibitors), minimally
      invasive surgical therapies or surgery. OAB is initially treated with behavioural
      therapy; if this is ineffective, pharmacotherapy (usually antimuscarinics) can be
      used. Patients with LUTS with a provisional diagnosis other than BPH or OAB, or
      with complications or poor response to pharmacotherapy, should be referred to a
      urologist.

PMID- 21728940
TI  - Government plans for public reporting of performance data in health care: the
      case for.

PMID- 21728941
TI  - Government plans for public reporting of performance data in health care: the
      case against.

PMID- 21728942
TI  - Gnathostomiasis in remote northern Western Australia: the first confirmed cases
      acquired in Australia.
AB  - A husband and wife became unwell after eating a fish from the Calder River in
      northern Western Australia. Gnathostomiasis was diagnosed, and treated with
      ivermectin and albendazole. Serological testing was positive for gnathostomiasis,
      and there has been no recurrence. These appear to be the first proven endemically
      acquired cases of gnathostomiasis in Australia, and demonstrate the difficulties
      in diagnosis and treatment.

PMID- 21728944
TI  - Change of HbA1c reporting to the new SI units.
AB  - An international consensus statement recommends that dual reporting of
      haemoglobin A (HbA(1c)) levels--in the current units (percentage) and Systeme
      International (SI) units (mmol/mol)--be used as an interim measure for a 2-year
      transition period before progressing towards the use of SI units only. This
      recommendation is supported by the Australasian Association of Clinical
      Biochemists, the Australian Diabetes Educators Association, the Australian
      Diabetes Society and the Royal College of Pathologists of Australasia. The SI
      units are a true measure of HbA(1c) and remove potential confusion between
      HbA(1c) values and blood glucose values.

PMID- 21728945
TI  - A couplet: a case of anal ulceration and another of inguinal swelling.

PMID- 21728946
TI  - What does the future hold for general medicine?
AB  - General medicine is being challenged by increasing numbers of patients who are
      presenting with multiple comorbidities and a decline in numbers of suitably
      trained personnel to manage these patients. A resurgence in generalist care, with
      collaboration between generalists and specialists, is the key to successfully
      managing patients who present with acute medical conditions. Better funded
      collaborative training programs for general physicians, which promote a diversity
      of skills and address clinical demand in a proscriptive manner, are needed.
      Research aimed at designing acute services to match local clinical demand is also
      required.

PMID- 21728947
TI  - Influenza vaccination of the egg-allergic individual.

PMID- 21728948
TI  - Ensuring safety of the 2011 trivalent influenza vaccine in young children.

PMID- 21728949
TI  - The changing profile of mental disorders among Disability Support Pension
      recipients.

PMID- 21728950
TI  - Migratory lung lesions in an elderly man.

PMID- 21728951
TI  - The implications of mandatory notification for clinician-researchers involved in
      observational research in health services.

PMID- 21728952
TI  - Development of clinical-quality registries in Australia: the way forward.

PMID- 21728953
TI  - Reasonable practice is not defensive practice.

PMID- 21728954
TI  - Consumer-friendly clinical trials information is here!

PMID- 21728955
TI  - Nonprofit pharma: solutions to what ails the industry.
AB  - Nonprofit organizations (NPOs) play an increasingly important role providing
      solutions to the significant challenges faced today by both large pharmaceutical
      and smaller biotechnology companies, not to mention academia. NPOs chartered for
      the public benefit are common in the USA and in selected other parts of the
      world. SRI International, originally founded as the Stanford Research Institute
      in 1946, is one of the largest and most successful independent NPOs. To provide a
      perspective on NPO business models, a number of SRI case studies spanning a broad
      range of technical and business initiatives will be summarized, including basic
      and contract research, discovery and development of new drugs and biologics,
      pharmaceutical and biotech research and development and contract services,
      technology pivots, company spin-ins and spin-outs, and the creation of new NPOs.
      How to bridge the National Institute of Health's "Valley of Death" and how to
      navigate the Food and Drug Administration's "Critical Path" will be discussed. We
      conclude with lessons learned about collaborations and routes to
      commercialization, along with food for thought for bioscience companies and
      outsourcing participants. Throughout, we attempt to explain why the role of NPOs
      is important to both the scientific and business communities and to patients and
      caregivers.

PMID- 21728956
TI  - Quasi-life self-organizing systems: based on ensembles of succinylated
      derivatives of interferon-gamma.
AB  - Research has been conducted on the chemical and biological properties of
      combinatorial succinylated derivatives of interferon-gamma with various levels of
      acylation, which create quasi-life, self-organizing ensembles. As a result of the
      research, it has been established that acylation by succinic anhydride of two
      lysines in the structure of interferon-gamma (Gammaferon) leads to both an
      increase in its affinity to cell receptors and a decrease in the time of maximum
      effect from 48 hours to 15 minutes. Moreover, treatment of cells with these
      interferon ensembles led to the shielding of 100% of the cells after a 15-minute
      incubation period, whereas native interferon shielded no more than 80% of the
      cells after 48 hours. Other ensembles also protected cells from viral action, but
      this protective effect did not exceed two hours in duration. The ensemble of
      succinylated interferon- gamma with two modified lysines may hold promise for the
      treatment of severe viral infections with fast courses, such as influenza and the
      diseases caused by the Ebola, Marburg, SARS, and other viruses.

PMID- 21728957
TI  - Anticholinesterasic, nematostatic and anthelmintic activities of pyridinic and
      pyrazinic compounds.
AB  - In the search for acetylcholinesterase inhibitors as a potential target for the
      discovery of anthelmintic drugs, a series of 27 pyridinic and pyrazinic compounds
      have been designed on the basis of molecular hybridization of two known AChE
      inhibitors, namely, tacrine and (-)-3-O-acetylspectaline, and on the concept of
      isosterism. The synthesized compounds generally presented moderate
      anticholinesterasic activities when compared with the positive control
      physostigmine, but one compound (ethyl 2-[(6-chloropyrazin-2-yl)sulfanyl]
      acetate) exhibited an in vitro ability to immobilize the root-knot nematode
      Meloidogyne incognita that was highly comparable to that of the positive control
      Temik. Moreover, in anthelmintic assays against the gastrointestinal parasitic
      nematode Nippostrongylus brasiliensis (L4), some of the compounds, such as (6
      chloropyrazin-2-yl)sulfanyl ethanol (32, EC50 = 33 nM), presented activities that
      were considerably stronger than that of the positive control albendazole (EC50 =
      340 nM). In the light of the positive results obtained in the anthelmintic
      evaluations, the acute oral toxicity of the representative compound diethyl 2,2'
      [(3-nitropyridine-2,6-diyl) bissulfanediyl] diacetate was determined in rats, and
      the drug was shown to be non-toxic at a dose of 2000 mg/kg. These results, allied
      with the relatively simple structures of the active compounds and their facile
      synthesis, highlight their potential use as anthelmintic or nematicidic agents.

PMID- 21728958
TI  - Cell signaling mechanisms of gustatory perception of lipids: can the taste cells
      be the target of anti-obesity agents?
AB  - It has been well propounded that there exists five basic taste modalities, e.g.,
      sweet, sour, bitter, salty and umami. Recent compelling evidence from rodents and
      human beings raises the possibility for an additional sixth taste modality
      devoted to the perception of lipids. A number of studies have suggested that
      lingual CD36, a glycoprotein, mainly expressed by circumvallate papillae of the
      tongue, might be implicated in the perception of dietary fat taste. G protein
      coupled receptors (GPCRs) are important signaling molecules for many aspects of
      cellular function. It has been recently shown that these receptors particularly
      GPR40 and GPR120 might also be involved in lipid taste perception. In this
      article, we highlight the cell activation mechanisms, responsible for the
      downstream cell signaling which might help understand the lipid-mediated
      regulation of feeding behavior, critically involved in the development of several
      diseases like obesity and other metabolic disorders. We also raise the question
      whether lipid gustatory cells can be the target of anti-obesity strategies.

PMID- 21728959
TI  - Progress towards discovery of antifibrotic drugs targeting synthesis of type I
      collagen.
AB  - Type I collagen is the most abundant protein in human body. Fibrosis is
      characterized by excessive synthesis of type I collagen in parenchymal organs. It
      is a leading cause of morbidity and mortality worldwide, about 45% of all natural
      deaths are attributable to some fibroproliferative disease. There is no cure for
      fibrosis. To find specific antifibrotic therapy targeting type I collagen,
      critical molecular interactions regulating its synthesis must be elucidated. Type
      I and type III collagen mRNAs have a unique sequence element at the 5' end, the
      5' stem-loop. This stem-loop is not found in any other mRNA. We cloned LARP6 as
      the protein which binds collagen 5' stem-loop with high affinity and specificity.
      Mutation of the 5' stem-loop or knock down of LARP6 greatly diminishes collagen
      expression. Mice with mutation of the 5' stem-loop are resistant to development
      of liver fibrosis. LARP6 associates collagen mRNAs with filaments composed of
      nonmuscle myosin; disruption of these filaments abolishes synthesis of type I
      collagen. Thus, LARP6 dependent collagen synthesis is the specific mechanism of
      high collagen expression seen in fibrosis. We developed fluorescence polarization
      (FP) method to screen for drugs that can inhibit binding of LARP6 to 5' stem-loop
      RNA. FP is high when LARP6 is bound, but decreases to low levels when the binding
      is competed out. Thus, by measuring decrease in FP it is possible to identify
      chemical compounds that can dissociate LARP6 from the 5' stem-loop. The method is
      simple, fast and suitable for high throughput screening.

PMID- 21728960
TI  - Assessing methods for characterising local and global structural and
      biomechanical properties of the trabecular bone network.
AB  - We apply noval techniques, the Scaling Index Method (SIM), which reveals local
      topology of the structure, and the Minkowski Functionals (MF), which provide four
      global topological characteristics, to assess strength of the trabecular network
      of the human bone. We compare capabilities of these methods with the standard
      analysis, biomechanical Finite Element Method (FEM) and morphological parameters,
      in prediction of bone strength and fracture risk. Our study is based on a sample
      of 151 specimens taken from the trabecular part of human thoracic and lumbar
      vertebrae in vitro, visualised using uCT imaging (isotropic resolution 26um) and
      tested by uniaxial compression. The sample of donors is heterogeneous, consisting
      of 58 male and 54 female cadavers with a mean age of 80 +/-10 years. To estimate
      the predictive power of the methods, we correlate texture measures derived from
      uCT images with the maximum compressive strength (MCS) as obtained in
      biomechanical tests. A linear regression analysis reveals that the failure load
      estimated by FEM shows the highest correlation with MCS (Pearson's correlation
      coefficient r=0.76). None of the methods in current study is superior to the FEM:
      morphometric parameters give r<0.5, global topological characteristics show
      r=0.73 for the first Minkowski Functional MF1, which coincides with bone volume
      fraction BV/TV and r=0.61 for the second Minkowski functional MF2, which
      coincides with bone surface BS. Although scaling indices provided by SIM
      correlate only moderately with MCS (r=0.55), texture measures based on the
      nonlinear combination of local (SIM) and global (MF) topological characteristics
      demonstrate high correlation with experimental MCS (r=0.74) and with failure load
      estimated by FEM (r=0.95). Additional advantage of the proposed texture measures
      is possibility to reveal the role of the topologically different trabecular
      structure elements for the bone strength.

PMID- 21728961
TI  - Targeting the multidrug ABCG2 transporter with flavonoidic inhibitors: in vitro
      optimization and in vivo validation.
AB  - This review describes the breast cancer resistance protein ABCG2 through its
      structure, functional roles and involvement in cell multidrug resistance,
      especially in cancer cells resistance to chemotherapeutics. The different types
      of known inhibitors are described, some being non-selective, since they also bind
      to other targets, and others being quite specific such as flavonoids. The
      different classes of active flavonoids and other polyphenols are described, some
      as plant natural compounds, but most of them being prepared and derivatized
      through medicinal chemistry. Quantitative structure-activity relationships of the
      ability of flavones, chalcones, xanthones, acridones and various
      benzopyrane/benzofurane derivatives to inhibit ABCG2-mediated drug efflux have
      led to pharmacophores and molecular models allowing to optimize the available hit
      compounds and to design new-generation lead compounds. Interestingly, inhibitory
      flavonoids are quite specific for ABCG2 versus ABCB1 and ABCC1, and appear either
      non-competitive or partially competitive towards mitoxantrone efflux. Most
      compounds do not inhibit ATPase activity, and are assumed not to be transported
      themselves by the transporter. Some acridones, firstly optimized in vitro as
      potent inhibitors, are indeed efficient in vivo, against human xenografts in SCID
      mice, more efficiently than gefitinib taken as a control. Future developments
      should open the way to more efficient/targeted modulators including (i) the
      potential interest of bimodulation by combining two different inhibitors, (ii)
      computer-assisted ligand-based drug design for getting more potent and more
      specific inhibitors, (iii) structure-based drug design from ABCG2 molecular
      models allowing in silico screening and docking of new inhibitors.

PMID- 21728962
TI  - Involvement of the ADAM 12 in thrombin-induced rat's VSMCs proliferation.
AB  - Cardiovascular disease is the largest single cause of mortality and its major
      underlying pathology is atherosclerosis. The proliferation of vascular smooth
      muscle cells (VSMCs) is a key event in the pathogenesis of the various vascular
      diseases, including atherosclerosis and hypertension. Thrombin (Thr) is involved
      in the abnormal proliferation of VSMCs associated with atherosclerosis and
      hypertension. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane
      metalloproteinases, belonging to the adamalysins group, that are distinct from
      matrix metalloproteinases (MMPs) in a way as they have an extracellular
      disintegrin domain and cytoplasmic domain that can associate with intracellular
      proteins. There is limited knowledge about the presence of ADAM metalloproteinase
      activity in Thr-induced VSMCs proliferation. Therefore, this review examines
      recent findings in signaling mechanisms employed by Thr in modulating the
      regulation of proliferation of VSMCs with particular emphasis on involvement of
      ADAM 12 which has been identified as an important mediator of VSMCs hypertrophy
      and vascular diseases. These findings are critical for understanding the role of
      Thr in vascular biology and vascular diseases.

PMID- 21728963
TI  - In vitro evaluation of chloroaluminum phthalocyanine nanoemulsion and low-level
      laser therapy on human skin dermal equivalents and bone marrow mesenchymal stem
      cells.
AB  - Nanotechnology and tissue engineering are promising scientific fields in the
      development of advanced materials useful to human health. This article describes
      the preparation of a nanocarrier for the controlled release of a photosensitizer
      compound associated with low-level light therapy for skin wound healing treatment
      and applicable to other skin diseases. A biological model was used as an in vitro
      skin equivalent based on a three-dimensional culture of fibroblasts and
      mesenchymal stem cells and denominated by dermal equivalent (DE). Results show
      that it is possible to use the photomodulation process to control the wound
      healing in a scratching process and to induce the biomolecules release, both of
      which are related with the inflammatory wound healing process. In the studies,
      the MMP-2 and MMP-9 expression from zymography analyses were evaluated. All
      results showed a dependence on enzymatic activity relating to lowlevel laser
      applications which indicates a potential application in wound healing processes
      based on phototherapy and nanotechnology.

PMID- 21728964
TI  - Nature inspired structured surfaces for biomedical applications.
AB  - Nature has created an array of superhydrophobic surfaces that possess water
      repellent, self-cleaning and anti-icing properties. These surfaces have a number
      of potential applications in the biomedical industry, as they have the potential
      to control protein adsorption and cell adhesion. Natural superhydrophobic
      surfaces are typically composed of materials with a low intrinsic surface free
      energy (e.g the cuticular waxes of lotus leaves and insect wings) with a
      hierarchical structural configuration. This hierarchical surface topography acts
      to decrease the contact area of water droplets in contact with the surface,
      thereby increasing the extent of the air/water interface, resulting in water
      contact angles greater than 150o. In order to employ these surfaces in
      biotechnological applications, fabrication techniques must be developed so that
      these multi-scale surface roughness characteristics can be reproduced.
      Additionally, these fabrication techniques must also be able to be applied to the
      material required for the intended application. An overview of some of the
      superhydrophobic surfaces that exist in nature is presented, together with an
      explanation of the theories of their wettability. Also included is a description
      of some of the biomedical applications of superhydrophobic surfaces and
      fabrication techniques that can be used to mimic superhydrophobic surfaces found
      in nature.

PMID- 21728965
TI  - Towards improved therapeutic CORMs: understanding the reactivity of CORM-3 with
      proteins.
AB  - The biological role of carbon monoxide (CO) has completely changed in the last
      decade. Beyond its widely feared toxicity, CO has revealed a very important
      biological activity as a signaling molecule with marked protective actions namely
      against inflammation, apoptosis and endothelial oxidative damage. Its direct use
      as a therapeutic gas showed significant and consistent positive results but also
      intrinsic severe limitations. The possibility of replacing the gas by pro-drugs
      acting as CO-Releasing Molecules (CO-RMs) has clearly been demonstrated with
      several experimental compounds. Transition metal carbonyls complexes have proven
      to be the most versatile experimental CO-RMs so far. Presently, the challenge is
      to equip them with drug-like properties to turn them into useful pharmaceuticals.
      This requires studying their interactions with biological molecules namely those
      that control their pharmacokinetic and ADME profiles like the plasma proteins. In
      this account we analyze these questions and review the existing interactions
      between Metal Carbonyls and proteins. The recently explored case of CORM-3 is
      revisited to exemplify the methodologies involved and the importance of the
      results for the understanding of the mode of action of such pro-drugs.

PMID- 21728966
TI  - Anti-inflammatory and antioxidant properties of a new arylidene-thiazolidinedione
      in macrophages.
AB  - Thiazolidinediones (TZDs) are a class of drugs used for treatment of type 2
      diabetes. However, the therapy with currently available TDZs (e.g. rosiglitazone)
      is associated with important side effects, such as edema and weight gain,
      suggesting that the investigation of alternative TZDs with better pharmacological
      properties is warranted. In this study, we investigated both anti-inflammatory
      and antioxidant properties of a new chemically modified TZD, the arylidene
      thiazolidinedione 5-(4-methanesulfonyl-benzylidene)-3-(4-nitrobenzyl)
      thiazolidine-2,4-dione (SF23), and compared the results to those obtained with
      rosiglitazone. We found that our SF23 displays a weaker affinity for PPARgamma,
      up-regulating in a lower magnitude the expression of both PPARgamma and CD36
      compared to rosiglitazone. In lipopolysaccharide (LPS)-stimulated macrophages,
      SF23 decreased nitrite production and attenuated the mRNA expression of both iNOS
      and COX-2. These anti-inflammatory effects were comparable to those obtained with
      rosiglitazone. Interestingly, SF23, but not rosiglitazone, prevented LPS-induced
      mitochondrial membrane hyperpolarization, apoptosis, reactive oxygen species
      (ROS) generation, and the expression of NADPH oxidase subunits, Nox1 and Nox2. In
      addition, in macrophages from Nrf2-/- mice, SF23 protected against LPSinduced
      cellular death and ROS production, whereas rosiglitazone was only able to protect
      normal Nrf2+/+ cells against oxidative injury, suggesting that, unlike
      rosiglitazone, the antioxidant activity of SF23 might be Nrf2-independent.
      Finally, in macrophages exposed to high concentrations of glucose, SF23 induced
      significant increases in the mRNA expression of glucose transporters, insulin
      receptor substrate and mitoNEET. Altogether, our data indicate that our new
      chemically modified TDZ displays similar anti-inflammatory properties, but
      superior antioxidant effects on the LPS-stimulated macrophages compared to
      rosiglitazone.

PMID- 21728967
TI  - Novel modular DNA aptamer for human thrombin with high anticoagulant activity.
AB  - Aptamers based on nucleic acids are a promising alternative to antibodies in
      therapy and diagnostics. Several DNA aptamers against human thrombin have been
      developed by selection from random libraries: a 15-mer and its derivatives, a 29
      mer, and a 31-mer. Some of them are patented and already under clinical trial.
      The 15-mer structure was determined by X-ray and NMR and turned out to be a
      monomolecular antiparallel G-quadruplex. The other aptamers mentioned above have
      higher inhibitory activity than the initial 15-mer, but there are not yet
      structural data explaining this phenomenon. Here, the initial 15-mer, 31-mer, and
      novel RA-36 aptamers are compared to establish the structure-function
      correlation, providing a solid ground for further rational aptameric drug design.
      For the molecular dynamic simulation of aptamers, the force field parmbsc0 was
      ported onto GROMACS, and the main stabilizing parameters were revealed, leading
      to the novel DNA aptamer RA-36. The functional properties of the DNA aptamers
      were studied by conventional coagulation tests, which do not directly elucidate
      the mechanism of thrombin inhibition by aptamers. Improved turbidimetric
      measurements provided data to develop detailed kinetics showing that the 31-mer
      and RA-36, in contrast to the 15-mer, are competitive inhibitors. These data
      revealed RA-36 to be an efficient thrombin inhibitor with a dose-dependent
      effect. Animal tests of the studied DNA aptamers suggested an unexpected species
      specificity of the novel RA-36.

PMID- 21728968
TI  - Diketo acids derivatives as dual inhibitors of human immunodeficiency virus type
      1 integrase and the reverse transcriptase RNase H domain.
AB  - The HIV-1 integrase (IN) and reverse transcriptase (RT) are essential enzymes in
      the virus cycle. RT is crucial for the retrotranscription of the RNA viral
      genome, while IN is involved in the insertion in host chromosome of the proviral
      double strand DNA produced by RT. This enzyme has two associated functions: the
      RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H
      (RNase H). The RNase H function catalyzes the selective hydrolysis of the RNA
      strand of the RNA:DNA heteroduplex replication intermediate. Since the discovery
      that catalytic cores of both HIV-1 RNase H and IN are folded in a very similar
      way, have very similar active site geometries, and show the same DDE triad
      absolutely required for catalytic activity, some researches were devoted to study
      IN and RNase H dual inhibitor. Our decennial interest in design and synthesis of
      IN inhibitors led us to study the activity of our compounds also on RNase H
      activity. The results of the activities showed by pyrrolyl and quinolonyl diketo
      acids are reported and discussed.

PMID- 21728969
TI  - Nanoparticle-derived non-viral genetic transfection at the blood-brain barrier to
      enable neuronal growth factor delivery by secretion from brain endothelium.
AB  - Brain capillary endothelial cells form the blood-brain barrier (BBB) that denotes
      a major restraint for drug entry to the brain. The identification of many new
      targets to treat diseases in the brain demands novel thinking in drug design as
      new therapeutics could often be proteins and molecules of genetic origins like
      siRNA, miRNA and cDNA. Such molecules are otherwise prevented from entry into the
      brain unless encapsulated in drug carriers. The desirable entry of such large,
      hydrophilic molecules should be made by formulation of particular drug carriers
      that will enable their transport into the brain endothelium, or even through the
      endothelium and into the brain. This manuscript reviews the potential of
      different drug-carriers for therapy to the brain with respect to their
      targetability, biocompatibility, toxicity and biodegradability.

PMID- 21728970
TI  - Pharmacotherapy of borderline personality disorder: a systematic review for
      publication purpose.
AB  - Borderline Personality Disorder (BPD) is a common disorder in psychiatric
      practice and drugs are widely used in its treatment, targeting symptom clusters,
      such as affective dysregulation, impulsive-behavioural dyscontrol, and cognitive
      perceptual symptoms. In last period, a growing number of studies on
      pharmacological treatment of BPD have been performed, but different proposals of
      treatment guidelines are not completely in accordance on drug indications for BPD
      patients. This article reviews double-blind randomized controlled trials
      comparing active drugs versus placebo and drugs versus drugs, published between
      1990 and 2010 and focused on the treatment of borderline personality disorder.
      Different classes of psychoactive agents, such as antipsychotics, mood
      stabilizers, antidepressants, and dietary supplementation were tested in BPD
      patients. More recent evidences suggest that mood stabilizers (topiramate,
      valproate and lamotrigine), second generation antipsychotics (olanzapine and
      aripiprazole) and omega-3 fatty acids can be useful to treat affective symptoms
      and impulsive-behavioural dyscontrol in BPD patients. Moreover, antipsychotics
      significantly improve cognitive symptoms in patients with BPD. SSRIs were found
      effective in decreasing severity of depressed mood, anxiety and anger, mainly in
      subjects with a concomitant affective disorder. Effects of antidepressants on
      impulsive behaviours are uncertain. Further studies are needed to improve methods
      of trials and confirm these findings.

PMID- 21728971
TI  - Current drug targets for modulating Alzheimer's amyloid precursor protein: role
      of specific micro-RNA species.
AB  - Alzheimer's disease (AD) is the most common form of dementia in the United States
      and is increasing in prevalence every year throughout the world. Recent clinical
      trial failures highlight the need for further insights into the molecular events
      that underlie the neurobiology of AD. Pathological aberrations in AD are believed
      to result, in part, from excess accumulation of amyloid-beta peptide (Abeta), a
      product of Abeta precursor protein (APP). Targeting APP levels would then be
      expected to reduce Abeta production in all forms of AD. Therefore, clarifying the
      regulatory network that governs APP expression is likely to reveal molecular
      players that could serve as novel drug targets. This review highlights recent
      work demonstrating the involvement of microRNA (miRNA) in this regulatory
      network. MiRNA are small, non-coding RNA that interact with target mRNA at sites
      of imperfect complementarity and mediate translational inhibition or transcript
      destabilization. We first review the neurobiology of AD and describe current
      therapeutic strategies. We then review transcriptional and post-transcriptional
      mechanisms utilized by cells to control APP expression. We conclude by
      highlighting recent work, including our own, which suggests miRNA are integral
      components of this regulatory framework and potential targets for future AD
      therapeutics.

PMID- 21728973
TI  - Nitric oxide and cyclic GMP signaling pathway as a focus for drug development.
AB  - Recent progress in understanding of the nitric oxide and cGMP signaling pathway
      provided evidence for mechanism of action of known drugs and identified novel
      targets for drug development. These discoveries resulted in numerous efforts in
      drug and formulation discovery. Some of the most promising approaches were
      applied for efficient therapies of various diseases.

PMID- 21728972
TI  - The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L
      cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's
      disease (AD).
AB  - Alzheimer's disease (AD) is the most common form of dementia in the older people
      and 7(th) leading cause of death in the United States. Deposition of amyloid-beta
      (Abeta) plaques, hyperphosphorylation of microtubule associated protein tau
      (MAPT), neuroinflammation and cholinergic neuron loss are the major hallmarks of
      AD. Deposition of Abeta peptides, which takes place years before the clinical
      onset of the disease can trigger hyperphophorylation of tau proteins and
      neuroinflammation, and the latter is thought to be primarily involved in neuronal
      and synaptic damage seen in AD. To date, four cholinesterase inhibitors or ChEI
      (tacrine, rivastigmine, donepezil and galantamine) and a partial NMDA receptor
      antagonist (memantine) are the only approved treatment options for AD. However,
      these drugs fail to completely cure the disease, which warrants a search for
      newer class of targets that would eventually lead to effective drugs for the
      treatment of AD. In addition to selected pharmacological agents, botanical and
      medicinal plant extracts are also being investigated. Apart from its culinary
      use, garlic (Allium sativum) is being used to treat several ailments like cancer
      and diabetes. Herein we have discussed the effects of a specific 'Aged Garlic
      Extract' (AGE) and one of its active ingredients, S-allyl-L-cysteine (SAC) in
      restricting several pathological cascades related to the synaptic degeneration
      and neuroinflammatory pathways associated with AD. Thus, based on the reported
      positive preliminary results reviewed herein, further research is required to
      develop the full potential of AGE and/or SAC into an effective preventative
      strategy for AD.

PMID- 21728975
TI  - Therapeutic potential of peptide motifs - part V.

PMID- 21728976
TI  - Novel neuropeptides as ligands of orphan G protein-coupled receptors.
AB  - Neuropeptides control a wide spectrum of physiological functions. They are
      central to our understanding of brain functions. They exert their actions by
      interacting with specific G protein-coupled receptors. We however have not found
      all the neuropeptides that exist in organisms. The search for novel neuropeptides
      is thus of great interest as it will lead to a better understanding of brain
      function and disorders. In this review, we will discuss the historical as well as
      the current approaches to neuropeptide discovery, with a particular emphasis on
      the orphan GPCR-based strategies. We will also discuss two novel peptides,
      neuropeptide S and neuromedin S, as examples of the impact of neuropeptide
      discovery on our understanding of brain functions. Finally, the challenges facing
      neuropeptide discovery will be discussed.

PMID- 21728977
TI  - Peptides as tight junction modulators.
AB  - The first step in drug absorption is the passage of drug molecules across
      epithelial cell sheets. Epithelial cell sheets are pivotal for the maintenance of
      homeostasis in the body by acting as a biological barrier that separates the
      inside of the body from the outside environment. Intercellular space between the
      adjacent epithelial cells is tightly sealed by tight junctions (TJs), which
      prevent solutes from freely moving across the epithelial cell sheets. Modulation
      of the TJ barrier has been a potent strategy for drug absorption. Absorption
      enhancers have been investigated since the 1980s, and sodium caprate is
      clinically used as an absorption enhancer. However, the biochemical constituents
      and structures of TJs were not elucidated until 1993. Occludin, a tetra
      transmembrane protein, was identified to be a structural component of TJs in
      1993. Claudin, another tetra-transmembrane protein, was identified as a
      structural and functional component of TJs in 1998. Modulation of occludin- or
      claudin-barrier is novel methods to enhance drug absorption. Recently, synthetic
      TJ-binding peptides, a kinase of claudin and peptide fragments of toxins have
      been developed. In the present review, we summarize the recent progress in TJ
      modulating peptides and discuss their potencies.

PMID- 21728978
TI  - Peptide mimetics of neurotrophins and their receptors.
AB  - Neurotrophic factors were originally identified based on their ability to prevent
      naturally occurring cell death in the developing nervous system. Many of these
      proteins also promote survival after injury or protect neurons in toxin-disease
      models in animals. In addition to neuroprotective effects, these factors exert
      trophic effects on neurons, stimulating increases in neuronal metabolism, cell
      size, and process outgrowth. These properties underlie expectations for
      neurorestoration, in which growth of new axons and synapses could lead to
      functional improvement, which is of great interest for those patients who are
      already significantly disabled by disease. Preclinical and clinical data suggest
      that subcutaneous or intravenous administration of neurotrophic factors may be
      effective for the treatment of peripheral nervous system diseases. However, even
      though these proteins are natural products, they do present specific problems
      when used as therapeutic agents. They cannot be given orally, present uncertain
      pharmacokinetic behavior, and large-scale production is labor and cost-intensive.
      Neurotrophic factor treatment of central nervous system diseases presents an even
      more complex scenario, since they are not able to cross the blood-brain barrier
      and must be given intracerebrally. Although there is an active search for
      alternative delivery strategies, for central nervous system diseases in
      particular the advantages of small molecule mimetics over proteins are evident.
      Small organic molecules can be modified to penetrate freely into the brain
      parenchyma and can be designed for oral administration. There are several
      possible approaches for replacing neurotrophic proteins with small molecule
      mimetics. For therapeutic use in the peripheral nervous system, neurotrophic
      proteins could be replaced by active peptide fragments with receptor binding
      properties similar to the full-length protein, but improved pharmacokinetic
      properties and lower production costs. In principle, it should be possible to
      replace the entire protein or fully active peptide fragment by a non-peptidic
      molecule binding to the same receptor site. It may be possible to regulate
      neurotrophic factor receptor activity by allosterically-acting molecules which
      influence the functional efficacy of the receptors. Other strategies include
      intracellular effector-targeting approaches, which are based on knowledge of
      signaling pathways involved in neuronal cell survival and demise, and which can
      be agonized or antagonized to promote neuroprotection. This chapter will begin
      with a brief overview on the biology neurotrophic proteins, followed with a
      description of strategies taken towards the development of small molecule
      mimetics for neurotrophic factors and the emerging drug candidates. The latter
      will encompass both receptor-directed as well as intracellular signalling
      approaches.

PMID- 21728979
TI  - Protection against tauopathy by the drug candidates NAP (davunetide) and D-SAL:
      biochemical, cellular and behavioral aspects.
AB  - Activity-dependent neuroprotective protein (ADNP) is essential for brain
      formation and partial deficiency in ADNP results in cognitive deficits coupled
      with tauopathy and neuronal cell death. Our previous results indicated that a
      peptide snippet from ADNP, NAPVSIPQ (NAP, generic name, davunetide) can restore
      in part ADNP deficiencies. NAP interacts with tubulin and this interaction is
      displaced by the NAP related peptide that is derived from activity-dependent
      neurotrophic factor (ADNF), SALLRSIPA (SAL) and its all D-amino acid peptide
      derivative (D-SAL, also known as AL-309). Both NAP and D-SAL were shown to
      protect neurons against amyloid beta toxicity however the mechanism of protection
      is still under investigation. In addition, NAP protects against tau
      hyperphosphorylation associated with ADNP deficiency, in vivo. To investigate
      whether the mechanism of in vitro neuroprotection relates to the in vivo
      protection against tauopathy and to draw potential additional parallelism between
      NAP and D-SAL, we asked if: 1]NAP and D-SAL protect against amyloid beta related
      tau hyperphosphorylation in vitro; and 2] D-SAL protects against
      haploinsufficiency in ADNP, inhibiting tauopathy in vivo. Assessment of NAP and D
      SAL neuroprotection in primary cortical neuro-glial cultures treated with amyloid
      beta showed that both peptides reduced toxin-related neuronal damage and
      protected against tau hyperphosphorylation. In vivo, chronic D-SAL administration
      protected against tau hyperphosphorylation associated with ADNP deficiency
      (ADNP+/- mice), showing for the first time protection against deficits in odor
      discrimination and in social recognition. These studies associate neuroprotection
      in vivo and in vitro and provide a broad base for future drug development based
      on NAP and D-SAL against multiple neurodegenerative conditions.

PMID- 21728980
TI  - Novel abeta isoforms in Alzheimer's disease - their role in diagnosis and
      treatment.
AB  - The last decades have witnessed an explosion in studies of the role of amyloid
      beta (Abeta) in the progress of the neurodegenerative disorder Alzheimer's
      disease (AD) and it is now widely accepted that Abeta is related to the
      pathogenesis of AD. For example, studies have shown that Abeta is neurotoxic and
      that the neurotoxicity of Abeta is related to its aggregation state. The
      concentration of the 42 amino acid form of Abeta (Abeta1-42) is reduced in the
      cerebrospinal fluid (CSF) from AD patients, which is believed to reflect the AD
      pathology with plaques in the brain acting as sinks. Less well investigated,
      however, is the ability of other Abeta isoforms to distinguish AD patients from
      controls and to identify treatment effects in clinical trials. Recently, novel C
      truncated forms of Abeta (Abeta1-14, Abeta1-15, and Abeta1-16) were identified in
      human CSF. The presence of these small peptides is consistent with a catabolic
      amyloid precursor protein cleavage pathway by beta- followed by alpha-secretase.
      It has been shown that Abeta1-14, Abeta1-15, and Abeta1-16 increase dose
      dependently in response to gamma-secretase inhibitor treatment while Abeta1-42
      levels are unchanged. Here, we review the many aspects of Abeta and its isoforms
      with special focus on their potential role as diagnostic and theragnostic
      markers.

PMID- 21728981
TI  - Anti-cancer peptides from ras-p21 and p53 proteins.
AB  - We have employed computer-based molecular modeling approaches to design peptides
      from the ras-p21 and p53 proteins that either induce tumor cell reversion to the
      untransformed phenotype or induce tumor cell necrosis without affecting normal
      cells. For rasp21, we have computed and superimposed the average low energy
      structures for the wild-type protein and oncogenic forms of this protein and
      found that specific domains change conformation in the oncogenic proteins. We
      have synthesized peptides corresponding to these and found that ras peptides, 35
      47 (PNC-7) and 96-110 (PNC-2), block oncogenic ras-p21-induced oocyte maturation
      but have no effect on insulin-induced oocyte maturation that requires activation
      of endogenous wild-type ras-p21. These results show signal transduction pathway
      differences between oncogenic and activated wild-type ras-p21. Both peptides,
      attached to a membrane-penetrating peptide (membrane residency peptide or MRP),
      either induce phenotypic reversion to the untransformed phenotype or tumor cell
      necrosis of several ras-transformed cell lines, but have no effect on the growth
      of normal cells. Using other computational methods, we have designed two
      peptides, PNC-27 and 28, containing HDM-2-protein-binding domain sequences from
      p53 linked on their C-termini to the MRP that induce pore formation in the
      membranes of a wide range of cancer cells but not any normal cells tested. This
      is due to the expression of HDM-2 in the cancer cell membrane that does not occur
      in normal cells. These peptides eradicate a highly malignant tumor in nude mice
      with no apparent side effects. Both ras and p53 peptides show promise as anti
      tumor agents in humans.

PMID- 21728982
TI  - Bioactive peptide-modified biomaterials for bone regeneration.
AB  - Bioactive biomaterials are desirable as tissue engineering scaffolds by virtue of
      their capability to mimic the natural environment of the extracellular matrix.
      Bioactive biomaterials have been achieved by incorporating synthetic short
      peptide sequences into suitable materials either by surface modification or by
      bulk incorporation. The goal is to enhance cell attachment and other basic
      functions. Bioactive peptides can be obtained from biological or chemically
      synthesized sources, increasing their specific cellular responses for tissue
      growth and development. Compared to using an entire growth factor in regenerative
      therapy, these peptides demonstrate potential advantages such as overcoming
      possible immunogenicity, being less susceptible to degradation, and producing
      fewer tumor-related side effects. Biomaterial scaffolds modified with peptides
      can provide biological ligands for cell-scaffold interactions that promote cell
      attachment, proliferation, and differentiation. Peptide-based biomaterial
      scaffolds can be fabricated to form two- and three-dimensional structures. This
      review discusses cell-binding, biominerailization inducing peptides, and receptor
      binding peptides for bone regeneration. This review also addresses issues related
      to peptide immobilization as well as potential complications that may develop as
      a result of using these versatile bioactive peptides. The development of self
      assembled peptide amphiphiles with the goal of generating new three-dimensional
      scaffolds for tissue engineering is also summarized.

PMID- 21728983
TI  - Peptides targeting estrogen receptor alpha-potential applications for breast
      cancer treatment.
AB  - Activation of the estrogen receptor alpha (ERalpha) is of prime importance for
      the development of hormone-dependent breast cancers. Hence, drugs able to impede
      the emergence of an active folding of ERalpha have been used for a long time as a
      first line therapeutic strategy. Aromatase inhibitors that block estradiol
      synthesis and / or antiestrogens that compete with hormone binding to the
      receptor are routinely prescribed. Unfortunately, emergence of tumor resistance
      almost invariably results from currently used antihormonal approaches. One may
      anticipate that a "multi-target" strategy affecting key regulatory domains
      distinct from ligand binding pocket of ERalpha may help to circumvent this
      problem. To reach this goal, the synthesis of peptides that may specifically
      inhibit intra- or inter-molecular interactions has been proposed. This paper
      describes functional motifs potentially suitable for the design of such
      antagonists. Activity of available peptidic and non-peptidic mimics of these
      motifs is also reviewed.

PMID- 21728984
TI  - Peptide and non-peptide antagonists targeting endothelin receptors in physiology
      and pathology.
AB  - As for other peptides such as bradykinin, neurokinins and angiotensins, peptide
      antagonists for endothelin-1 (ET-1) have been early on developed towards the
      pharmacological characterization of both ET(A) and ET(B) receptors.
      Interestingly, unlike the previously mentioned three peptides, receptors for ET-1
      were cloned and purified prior to the report of ET(A)and ET(B)receptor
      antagonists such as BQ-123 and BQ-788. The availability of such pharmacological
      tools and the use of molecular approaches have certainly fast-tracked the
      development of non-peptide ET receptor antagonists for clinical applications.
      Albeit rapid degradation by gastric enzymes and short half-life in plasma of
      peptide receptor antagonists limit their use in clinical settings, those
      molecules have been of importance in the identification of mediators and
      modulators of ET-1 induced properties in vitro and in vivo, as described further
      in this review. Peptide antagonists acting selectively or, with equivalent
      affinities against ET(A)and ET(B)receptors were reported prior to the advent of
      clinically relevant non-peptide blockers such as Bosentan. Confounding mechanisms
      involving, for example, the endogenous modulators nitric oxide and prostacyclin
      as well as allosteric interactions between ET receptor types, have also been
      clarified with the use of peptide antagonists for endothelins. Finally, peptide
      antagonists were also used to identify the precise pharmacology of ET-1
      precursors such as big-endothelin-1 and ET-1 (1-31). The present review will thus
      attempt to summarize the knowledge to date and future perspectives related to use
      of peptide antagonists targeting endothelin receptors in physiological and
      pathological settings.

PMID- 21728985
TI  - Peptoids: bio-inspired polymers as potential pharmaceuticals.
AB  - Peptoids are a developing class of peptide-like oligomers originally invented for
      drug discovery in the early 1990s. While peptides hold great promise for
      therapeutic applications, current development of peptide-based pharmaceuticals is
      hindered by their potential for misfolding and aggregation, and particularly, for
      rapid in vivo degradation post-administration. Researchers have investigated
      alternative peptide-like constructs that may be able to circumvent such
      complications. Peptoids comprise a peptide-based backbone and N-substituted
      glycines for side chain residues, resulting in complete protease-resistance.
      Synthesis of peptoid sequences up to 50 units in length allows for controlled
      sequence composition and incorporation of diverse side chain chemistries. Though
      the landscape of peptoid structure is not clearly defined, secondary, tertiary,
      loop, turn, and random structures have been identified. As protease-resistant
      isomers of peptides, peptoids are being developed as versatile molecular tools in
      biochemistry and biophysics, and are becoming attractive candidates for
      therapeutic and diagnostic applications. Peptoids have thus far demonstrated
      bioactivity as protein mimics and as replacements for small molecule drugs. In
      this review, we discuss the most recent advances in peptoid research on the
      therapeutic front in the last few years, including in vitro and in vivo studies
      in the fields of lung surfactant therapy, antimicrobial agents, diagnostics, and
      cancer. We particularly focus on the biophysical activity of lipid-associated
      peptoids and their potential therapeutic applications.

PMID- 21728986
TI  - Antimalarial peptides: the long and the short of it.
AB  - Antimicrobial peptides include a diverse array of both natural and synthetic
      molecules varying greatly in size, charge, hydrophobicity and secondary
      structural features. Although better known as antibacterial agents, many peptides
      have demonstrated activity against the malarial parasite Plasmodium either in its
      vertebrate blood stages or mosquito stages or both. The antimalarial peptides
      reviewed here consist of (i) cationic, amphipathic 'host-defence' peptides
      including some (e.g. defensins and cecropins) that are naturally produced by
      mosquitos, (ii) other membrane-active peptide antibiotics such as gramicidins,
      (iii) hydrophobic peptides, most notably cyclosporins, (iv) thiopeptides, such as
      thiostrepton, and (v) some other naturally occurring or synthetic peptides. Many
      of these peptides affect membrane integrity and some are selective for parasite
      membranes over those of the host, while others are thought to have more specific
      intracellular targets. The mechanisms of action of the majority of antimalarial
      peptides are however either uncertain or totally unknown. Very few of these
      agents have been tested in rodent malaria models and none has undergone
      significant pre-clinical or clinical development for malaria. Issues such as
      metabolic lability, high cost, and a lack of information about systemic toxicity
      are likely to be serious obstacles to further development of peptides as
      antimalarial drugs. On the other hand, they offer potential advantages, including
      the possibility of being much less prone to resistance than the drugs in current
      use. An alternative to conventional chemotherapy, namely the release of malaria
      refractory, transgenic mosquitos overproducing antimalarial peptides, has already
      passed the 'proof of concept' stage.

PMID- 21728987
TI  - Kinins as therapeutic agents in cardiovascular and renal diseases.
AB  - A fair amount of data indicates that bradykinin and lysyl-bradykinin exert
      arterial, cardiac and renal effects which afford protection against organ damage
      in diseases, especially in the settings of ischemia or diabetes. The concept of
      kinins acting as therapeutic agents is supported by the wide use of angiotensin I
      converting enzyme (ACE) inhibitors. These inhibitors indeed potentiate kinin
      action by inhibiting kinin degradation. Experimental evidence strongly suggests
      that the cardiac and renal effects of ACE inhibitors are due, at least in part,
      to kinins. Angiotensin AT1 receptor antagonists act also partly through kinins.
      This paper reviews available evidence supporting a role for kinins in the
      therapeutic effect of current drugs. It then discusses the opportunity to develop
      new drugs based on kinin action. Direct activation of the kinin B2 receptor by
      pharmacological agonists might provide higher therapeutic benefit than existing
      kinin- potentiating drugs. Possible occurrence of side effects is however a
      concern.

PMID- 21728988
TI  - Using a novel AdaBoost algorithm and Chou's Pseudo amino acid composition for
      predicting protein subcellular localization.
AB  - For a protein, an important characteristic is its location or compartment in a
      cell. This is because a protein has to be located in its proper position in a
      cell to perform its biological functions. Therefore, predicting protein
      subcellular location is an important and challenging task in current molecular
      and cellular biology. In this paper, based on AdaBoost.ME algorithm and Chou's
      PseAAC (pseudo amino acid composition), a new computational method was developed
      to identify protein subcellular location. AdaBoost.ME is an improved version of
      AdaBoost algorithm that can directly extend the original AdaBoost algorithm to
      deal with multi-class cases without the need to reduce it to multiple two-class
      problems. In some previous studies the conventional amino acid composition was
      applied to represent protein samples. In order to take into account the sequence
      order effects, in this study we use Chou's PseAAC to represent protein samples.
      To demonstrate that AdaBoost.ME is a robust and efficient model in predicting
      protein subcellular locations, the same protein dataset used by Cedano et al.
      (Journal of Molecular Biology, 1997, 266: 594-600) is adopted in this paper. It
      can be seen from the computed results that the accuracy achieved by our method is
      better than those by the methods developed by the previous investigators.

PMID- 21728989
TI  - Characterization of nuclear glutamate dehydrogenase of chicken liver and brain.
AB  - Glutamate dehydrogenase (GDH) enzyme is recently being reported to be present in
      the nucleus in addition to the mitochondria in a number of organisms. Here we
      investigated the distribution of GDH in liver and brain tissues of chicken.
      Polyclonal anti-GDH antibody against bovine GDH was raised by us, which was later
      shown to be immunereactive to chicken GDH. The nuclear and the mitochondrial
      extracts from liver and brain tissues of chicken were made as described. By
      quantitative immunoreactivity, it was revealed that the nuclear GDH expressed in
      comparable efficiencies in the liver and brain. However, the activity of the
      brain nuclear GDH was lower than the liver counterparts. The allosteric
      regulation pattern for the brain nuclear GDH was also different from the other
      corresponding fractions and it was speculated that the brain nuclear GDH was
      inactive. The liver and brain nuclear GDH were purified to homogeneity and
      comparison of specific activities of both the GDH ruled out the existence of any
      inhibitor in the brain nuclear GDH. It is hypothesized that the inactivation of
      the brain nuclear GDH in chicken could be due to some already known
      posttranslational modification. The present report throws light on the
      differential regulation pattern of GDH enzyme.

PMID- 21728990
TI  - Evidences of monomer, dimer and trimer of recombinant human cyclophilin A.
AB  - Cyclophilin A (CyPA) is a cytosolic receptor of immunosuppressive drug
      cyclosporin A (CsA) which possesses peptidyl-prodyl cis/trans isomerase (PPIase)
      activity. The recombinant human CyPA (rhCyPA) gene has been expressed in E. coli
      M15. Purification was performed using salting-out, as well as Sephacryl S-100 and
      DEAE-Sepharose CL-6B column chromatography. The molecular weight is about 18 kDa,
      confirmed by SDS-PAGE and mass spectrum. The results of Native-PAGE and
      immunoblotting showed the existence of three bands, which agreed well with the
      gel filtration results. The molecular mass of the three bands determined via CTAB
      gel electrophoresis and SDS-PAGE (rhCyPA cross-linked with glutaraldehyde) was 18
      kDa, 36 kDa and 54 kDa respectively. Further more, the native rhCyPA and the
      cross-linked rhCyPA had the similar chromatographic behavior in gel filtration.
      All of the evidences above suggest that rhCyPA exists in forms of monomer, dimer
      and trimer. Moreover, we observed that even at low protein concentrations CyPA
      largely occurs as a dimer in solution, and enzyme kinetic parameters showed that
      activity of dimer was much higher than monomer or trimer, which probably have
      some biological significances.

PMID- 21728991
TI  - Ganoderma lucidum: a source for novel bioactive lectin.
AB  - Ganoderma lucidum is known for its high medicinal value, clinically used in
      treatment for various diseases. We have selected this mushroom for isolation of
      novel bioactive lectin. The isolation procedure comprised of ion-exchange
      chromatography on DEAE- cellulose and affinity chromatography on Affi-gel blue
      gel. Purified lectin was monomer with a molecular mass of 15 kDa, determined by
      SDS-PAGE, Gel filtration, MALDI-ToF. It showed hemagglutinating activity against
      both human and animal erythrocytes. The hemagglutination activity was not
      inhibited by simple sugars but inhibited by glycoproteins. The activity was
      maximal at pH range 4.0-9.0 and at temperature up to 60 degrees  C. The
      hemagglutination activity was stable even in the presence of 10mM EDTA and other
      divalent metal cations such as CaCl2, MgCl2, ZnCl2, and MnCl2. Lectin was shown
      antifungal activity against following pathogens Fusarium oxysporium, Penicillium
      chrysogenum, Aspergillus Niger, Colletotrichum musae, Botrytis cinerea,
      Trichophyton rubrum, Trichophyton tonsurans, Trichophyton interdigitale,
      Epidermophyton floccosum and Microsporum canis.

PMID- 21728992
TI  - Predicting the activity of ACE inhibitory peptides with a novel mode of pseudo
      amino acid composition.
AB  - In this study, physicochemical scale (P-scale), was recruited as a novel set of
      physicochemical descriptors derived from component analysis on four short of
      physicochemical properties variables (hydrophobic, electronic, steric and
      hydrogen bond contribution) of 20 coded amino acids, By using partial least
      squares (PLS), we applied P-scale for the study of quantitative structure 
      activity relationship models (QASRs) on three angiotensin I converting enzyme
      (ACE) inhibitory peptides datasets (58 dipeptides, 55 tripeptides, and 50
      tetrapeptides).The results of QSARs were superior to that of the earlier studies,
      with correlation coefficient (r(2)) and cross-validated(q(2)) equal to 0.902,
      0.86; 0.985, 0.951 and 0.872, 0.77, respectively. By analysis, hydrophobic and
      steric properties of ACE-inhibitory peptide sequences play important roles in
      their bioactivities, and novel peptide sequence could be designed based on these
      properties of the amino acid residues. These results showed that P-scale
      descriptors can well represent the peptide sequence. Furthermore, the robust
      models show that P-scale descriptors can be further expanded for polypeptides and
      can serve as a useful quantitative tool for the rational drug design and
      discovery.

PMID- 21728993
TI  - Laforin, a dual-specificity phosphatase involved in Lafora disease, is
      phosphorylated at Ser25 by AMP-activated protein kinase.
AB  - Lafora progressive myoclonus epilepsy [LD (Lafora disease)] is a fatal autosomal
      recessive neurodegenerative disorder caused by loss-of-function mutations in
      either the EPM2A gene, encoding the dual-specificity phosphatase laforin, or the
      EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others
      showed that laforin and malin form a functional complex that regulates multiple
      aspects of glycogen metabolism, and that the interaction between laforin and
      malin is enhanced by conditions activating AMPK (AMP-activated protein kinase).
      In the present study, we demonstrate that laforin is a phosphoprotein, as
      indicated by two-dimensional electrophoresis, and we identify Ser(25) as the
      residue involved in this modification. We also show that Ser(25) is
      phosphorylated both in vitro and in vivo by AMPK. Lastly, we demonstrate that
      this residue plays a critical role for both the phosphatase activity and the
      ability of laforin to interact with itself and with previously established
      binding partners. The results of the present study suggest that phosphorylation
      of laforin-Ser(25) by AMPK provides a mechanism to modulate the interaction
      between laforin and malin. Regulation of this complex is necessary to maintain
      normal glycogen metabolism. Importantly, Ser(25) is mutated in some LD patients
      (S25P), and our results begin to elucidate the mechanism of disease in these
      patients.

PMID- 21728994
TI  - The phosphatidylinositol transfer protein RdgBbeta binds 14-3-3 via its
      unstructured C-terminus, whereas its lipid-binding domain interacts with the
      integral membrane protein ATRAP (angiotensin II type I receptor-associated
      protein).
AB  - PITPs [PI (phosphatidylinositol) transfer proteins] bind and transfer PI between
      intracellular membranes and participate in many cellular processes including
      signalling, lipid metabolism and membrane traffic. The largely uncharacterized
      PITP RdgBbeta (PITPNC1; retinal degeneration type B beta), contains a long C
      terminal disordered region following its defining N-terminal PITP domain. In the
      present study we report that the C-terminus contains two tandem phosphorylated
      binding sites (Ser(274) and Ser(299)) for 14-3-3. The C-terminus also contains
      PEST sequences which are shielded by 14-3-3 binding. Like many proteins
      containing PEST sequences, the levels of RdgBbeta are regulated by proteolysis.
      RdgBbeta is degraded with a half-life of 4 h following ubiquitination via the
      proteasome. A mutant RdgBbeta which is unable to bind 14-3-3 is degraded even
      faster with a half-life of 2 h. In vitro, RdgBbeta is 100-fold less active than
      PITPalpha for PI transfer, and RdgBbeta proteins (wild-type and a mutant that
      cannot bind 14-3-3) expressed in COS-7 cells or endogenous proteins from heart
      cytosol do not exhibit transfer activity. When cells are treated with PMA, the
      PITP domain of RdgBbeta interacts with the integral membrane protein ATRAP
      (angiotensin II type I receptor-associated protein; also known as AGTRAP) causing
      membrane recruitment. We suggest that RdgBbeta executes its function following
      recruitment to membranes via its PITP domain and the C-terminal end of the
      protein could regulate entry to the hydrophobic cavity.

PMID- 21728995
TI  - Crystal structures and kinetic studies of human Kappa class glutathione
      transferase provide insights into the catalytic mechanism.
AB  - GSTs (glutathione transferases) are a family of enzymes that primarily catalyse
      nucleophilic addition of the thiol of GSH (reduced glutathione) to a variety of
      hydrophobic electrophiles in the cellular detoxification of cytotoxic and
      genotoxic compounds. GSTks (Kappa class GSTs) are a distinct class because of
      their unique cellular localization, function and structure. In the present paper
      we report the crystal structures of hGSTk (human GSTk) in apo-form and in complex
      with GTX (S-hexylglutathione) and steady-state kinetic studies, revealing
      insights into the catalytic mechanism of hGSTk and other GSTks. Substrate binding
      induces a conformational change of the active site from an 'open' conformation in
      the apo-form to a 'closed' conformation in the GTX-bound complex, facilitating
      formations of the G site (GSH-binding site) and the H site (hydrophobic substrate
      binding site). The conserved Ser(16) at the G site functions as the catalytic
      residue in the deprotonation of the thiol group and the conserved Asp(69),
      Ser(200), Asp(201) and Arg(202) form a network of interactions with gamma
      glutamyl carboxylate to stabilize the thiolate anion. The H site is a large
      hydrophobic pocket with conformational flexibility to allow the binding of
      different hydrophobic substrates. The kinetic mechanism of hGSTk conforms to a
      rapid equilibrium random sequential Bi Bi model.

PMID- 21728996
TI  - A phospholamban-tethered cardiac Ca2+ pump reveals stoichiometry and dynamic
      interactions between the two proteins.
AB  - To study PLB (phospholamban) inhibition of the cardiac Ca(2+) pump [SERCA2a
      (sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2a)], a fusion protein (SER-20G
      PLB) was engineered by tethering SERCA2a with PLB through a 20-glycine residue
      chain, allowing the PLB tether to either bind to or dissociate from the
      inhibition site on SERCA2a. When expressed in insect cells, SER-20G-PLB produced
      active Ca(2+) uptake, which was stimulated by the anti-PLB antibody, both similar
      to that which occurred with the control sample co-expressing WT (wild-type)
      SERCA2a and WT-PLB. The K(Ca) values of Ca(2+)-dependent ATPase were similar for
      SER-20G-PLB (0.29+/-0.02 MUM) and for the control sample (0.30+/-0.02 MUM), both
      greater than 0.17+/-0.01 MUM for WT-SERCA2a expressed alone. Thus SER-20G-PLB
      retains a fully active Ca(2+) pump, but its apparent Ca(2+) affinity was
      decreased intrinsically by tethered PLB at a 1:1 molar stoichiometry. Like WT
      PLB, SER-20G-PLB ran as both monomers and homo-pentamers on SDS/PAGE. As Ca(2+)
      concentrations increase from 0 to the micromolar range, the proportion of non
      inhibiting pentamers increased from 32% to 52%, suggesting that Ca(2+) activation
      of the pump completely dissociates the PLB tether from the inhibition site on
      SERCA2a, with concurrent association of PLB pentamers. Collectively, the
      regulation of SERCA2a is achieved through the Ca(2+)-dependent equilibria
      involving PLB association and dissociation from SERCA2a, and assembling and
      disassembling of SER-20G-PLB pentamers.

PMID- 21728997
TI  - CREBL2, interacting with CREB, induces adipogenesis in 3T3-L1 adipocytes.
AB  - The factors that influence preadipocyte determination remain poorly understood.
      In the present paper, we report that CREBL2 [CREB (cAMP-response-element-binding
      protein)-like 2], a novel bZIP_1 protein, is up-regulated during MDI-induced
      preadipocyte differentiation. During both overexpression and under physiological
      conditions, CREBL2 interacted and was entirely co-localized with CREB.
      Overexpression of CREBL2 was sufficient to promote adipogenesis via up-regulating
      the expression of PPARgamma (peroxisome-proliferator-activated receptor gamma)
      and C/EBPalpha (CCAAT/enhancer-binding protein alpha) and accelerate lipogenesis
      accompanied with increased GLUT (glucose transporter) 1 and GLUT4. CREBL2
      knockdown restrained adipogenic conversion and lipogenesis. Additionally,
      depletion of CREB could completely block the effects of overexpressed CREBL2,
      whereas an increase in CREB could not drive adipogenesis in the absence of
      CREBL2, indicating that the roles for CREBL2 on adipogenesis were CREB-dependent.
      Furthermore, siCREBL2 [siRNA (short interfering RNA) against CREBL2] could down
      regulate CREB transcriptional activity and suppress CREB phosphorylation. CREB
      knockdown decreased the CREBL2 protein levels and vice versa. Collectively, the
      results of the present study indicate that CREBL2 plays a critical role in
      adipogenesis and lipogenesis via interaction with CREB.

PMID- 21728998
TI  - l(2)01810 is a novel type of glutamate transporter that is responsible for
      megamitochondrial formation.
AB  - l(2)01810 causes glutamine-dependent megamitochondrial formation when it is
      overexpressed in Drosophila cells. In the present study, we elucidated the
      function of l(2)01810 during megamitochondrial formation. The overexpression of
      l(2)01810 and the inhibition of glutamine synthesis showed that l(2)01810 is
      involved in the accumulation of glutamate. l(2)01810 was predicted to contain
      transmembrane domains and was found to be localized to the plasma membrane. By
      using (14)C-labelled glutamate, l(2)01810 was confirmed to uptake glutamate into
      Drosophila cells with high affinity (K(m)=69.4 MUM). Also, l(2)01810 uptakes
      glutamate in a Na(+)-independent manner. Interestingly, however, this uptake was
      not inhibited by cystine, which is a competitive inhibitor of Na(+)-independent
      glutamate transporters, but by aspartate. A signal peptide consisting of 34 amino
      acid residues targeting to endoplasmic reticulum was predicted at the N-terminus
      of l(2)01810 and this signal peptide is essential for the protein's localization
      to the plasma membrane. In addition, l(2)01810 has a conserved functional domain
      of a vesicular-type glutamate transporter, and Arg(146) in this domain was found
      to play a key role in glutamate transport and megamitochondrial formation. These
      results indicate that l(2)01810 is a novel type of glutamate transporter and that
      glutamate uptake is a rate-limiting step for megamitochondrial formation.

PMID- 21728999
TI  - Ultrastructure of cilia and flagella - back to the future!
AB  - Eukaryotic cilia and flagella perform motility and sensory functions which are
      essential for cell survival in protozoans, and to organism development and
      homoeostasis in metazoans. Their ultrastructure has been studied from the early
      beginnings of electron microscopy, and these studies continue to contribute to
      much of our understanding about ciliary biology. In the light of the progress
      made in the visualization of cellular structures over the last decade, we revisit
      the ultrastructure of cilia and flagella. We briefly describe the typical
      features of a 9+2 axoneme before focusing extensively on the transition zone, the
      ciliary necklace, the singlet zone, the ciliary cap and the ciliary crown. We
      discuss how the singlet zone is linked to sensory and/or motile function, the
      contribution of the ciliary crown to ovocyte and mucosal propulsion, and the
      relationship between the ciliary cap and microtubule growth and shortening, and
      its relation to ciliary beat. We further examine the involvement of the
      transition zone/the ciliary necklace in axonemal stabilization, autotomy and as a
      diffusion barrier.

PMID- 21729000
TI  - Is fat so bad? Modulation of endoplasmic reticulum stress by lipid droplet
      formation.
AB  - LDs (lipid droplets) have long been considered as inert particles used by the
      cells to store fatty acids and sterols as esterified non-toxic lipid species
      (i.e. triacylglycerols and steryl esters). However, accumulating evidence
      suggests that LDs behave as a dynamic compartment, which is involved in the
      regulation of several aspects of the homoeostasis of their originating organelle,
      namely the ER (endoplasmic reticulum). The ER is particularly sensitive to
      physiological/pathological stimuli, which can ultimately induce ER stress. In the
      present review, after considering the basic mechanisms of LD formation and the
      signal cascades leading to ER stress, we focus on the connections between these
      two pathways. Taking into consideration recent data from the literature, we will
      try to draw possible mechanisms for the role of LDs in the regulation of ER
      homoeostasis and in ER-stress-related diseases.

PMID- 21729002
TI  - The forgotten face of regular physical exercise: a 'natural' anti-atherogenic
      activity.
AB  - Humans are not programmed to be inactive. The combination of both accelerated
      sedentary lifestyle and constant food availability disturbs ancient metabolic
      processes leading to excessive storage of energy in tissue, dyslipidaemia and
      insulin resistance. As a consequence, the prevalence of Type 2 diabetes, obesity
      and the metabolic syndrome has increased significantly over the last 30 years. A
      low level of physical activity and decreased daily energy expenditure contribute
      to the increased risk of cardiovascular morbidity and mortality following
      atherosclerotic vascular damage. Physical inactivity leads to the accumulation of
      visceral fat and consequently the activation of the oxidative stress/inflammation
      cascade, which promotes the development of atherosclerosis. Considering physical
      activity as a 'natural' programmed state, it is assumed that it possesses
      atheroprotective properties. Exercise prevents plaque development and induces the
      regression of coronary stenosis. Furthermore, experimental studies have revealed
      that exercise prevents the conversion of plaques into a vulnerable phenotype,
      thus preventing the appearance of fatal lesions. Exercise promotes
      atheroprotection possibly by reducing or preventing oxidative stress and
      inflammation through at least two distinct pathways. Exercise, through laminar
      shear stress activation, down-regulates endothelial AT1R (angiotensin II type 1
      receptor) expression, leading to decreases in NADPH oxidase activity and
      superoxide anion production, which in turn decreases ROS (reactive oxygen
      species) generation, and preserves endothelial NO bioavailability and its
      protective anti-atherogenic effects. Contracting skeletal muscle now emerges as a
      new organ that releases anti-inflammatory cytokines, such as IL-6 (interleukin
      6). IL-6 inhibits TNF-alpha (tumour necrosis factor-alpha) production in adipose
      tissue and macrophages. The down-regulation of TNF-alpha induced by skeletal
      muscle-derived IL-6 may also participate in mediating the atheroprotective effect
      of physical activity.

PMID- 21729003
TI  - Structural and mechanistic insight into the ferredoxin-mediated two-electron
      reduction of bilins.
AB  - PEB (phycoerythrobilin) is one of the major open-chain tetrapyrrole molecules
      found in cyanobacterial light-harvesting phycobiliproteins. In these organisms,
      two enzymes of the ferredoxin-dependent bilin reductase family work in tandem to
      reduce BV (biliverdin IXalpha) to PEB. In contrast, a single cyanophage-encoded
      enzyme of the same family has been identified to catalyse the identical reaction.
      Using UV-visible and EPR spectroscopy we investigated the two individual
      cyanobacterial enzymes PebA [15,16-DHBV (dihydrobiliverdin):ferredoxin
      oxidoreductase] and PebB (PEB:ferredoxin oxidoreductase) showing that the two
      subsequent reactions catalysed by the phage enzyme PebS (PEB synthase) are
      clearly dissected in the cyanobacterial versions. Although a highly conserved
      aspartate residue is critical for both reductions, a second conserved aspartate
      residue is only involved in the A-ring reduction of the tetrapyrrole in PebB and
      PebS. The crystal structure of PebA from Synechococcus sp. WH8020 in complex with
      its substrate BV at a 1.55 A (1 A=0.1 nm) resolution revealed further insight
      into the understanding of enzyme evolution and function. Based on the structure
      it becomes obvious that in addition to the importance of certain catalytic
      residues, the shape of the active site and consequently the binding of the
      substrate highly determines the catalytic properties.

PMID- 21729004
TI  - Pathway analysis of NAD+ metabolism.
AB  - NAD(+) is well known as a crucial cofactor in the redox balance of metabolism.
      Moreover, NAD(+) is degraded in ADP-ribosyl transfer reactions, which are
      important components of multitudinous signalling reactions. These include
      reactions linked to DNA repair and aging. In the present study, using the concept
      of EFMs (elementary flux modes), we established all of the potential routes in a
      network describing NAD(+) biosynthesis and degradation. All known biosynthetic
      pathways, which include de novo synthesis starting from tryptophan as well as the
      classical Preiss-Handler pathway and NAD(+) synthesis from other vitamin
      precursors, were detected as EFMs. Moreover, several EFMs were found that degrade
      NAD(+), represent futile cycles or have other functionalities. The systematic
      analysis and comparison of the networks specific for yeast and humans document
      significant differences between species with regard to the use of precursors,
      biosynthetic routes and NAD(+)-dependent signalling.

PMID- 21729005
TI  - TGFbeta (transforming growth factor beta) and keratocyte motility in 24 h
      zebrafish explant cultures.
AB  - Fish keratocytes are used as a model system for the study of the mechanics of
      cell motility because of their characteristic rapid, smooth gliding motion, but
      little work has been done on the regulation of fish keratocyte movement. As
      TGFbeta (transforming growth factor beta) plays multiple roles in primary human
      keratinocyte cell migration, we investigated the possible involvement of TGFbeta
      in fish keratocyte migration. Studying the involvement of TGFbeta1 in 24 h
      keratocyte explant allows the examination of the cells before alterations in
      cellular physiology occur due to extended culture times. During this initial
      period, TGFbeta levels increase 6.2-fold in SFM (serum-free medium) and 2.4-fold
      in SFM+2% FBS (fetal bovine serum), while TGFbeta1 and TGFbetaRII (TGFbeta
      receptor II) mRNA levels increase ~3- and ~5-fold respectively in each culture
      condition. Two measures of motility, cell sheet area and migration distance, vary
      with the amount of exogenous TGFbeta1 and culture media. The addition of 100
      ng/ml exogenous TGFbeta1 in SFM increases both measures [3.3-fold (P = 4.5*10-5)
      and 26% (P = 2.1*10-2) respectively]. In contrast, 100 ng/ml of exogenous
      TGFbeta1 in medium containing 2% FBS decreases migration distance by 2.1-fold (P
      = 1.7*10-7), but does not affect sheet area. TGFbeta1 (10 ng/ml) has little
      effect on cell sheet area in SFM cultures, but leads to a 1.8-fold increase (P =
      1.5*10-2) with 2% FBS. The variable response to TGFbeta1 may be, at least in
      part, explained by the effect of 2% FBS on cell morphology, mode of motility and
      expression of endogenous TGFbeta1 and TGFbetaRII. Together, these results suggest
      that expression of TGFbeta and its receptor are up-regulated during zebrafish
      keratocyte explant culture and that TGFbeta promotes fish keratocyte migration.

PMID- 21729006
TI  - The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress
      related autophagy in HeLa cells.
AB  - The ability of human cells to defend against viruses originating from distant
      species has long been ignored. Owing to the pressure of natural evolution and
      human exploration, some of these viruses may be able to invade human beings. If
      their 'fresh' host had no defences, the viruses could cause a serious pandemic,
      as seen with HIV, SARS (severe acute respiratory syndrome) and avian influenza
      virus that originated from chimpanzees, the common palm civet and birds,
      respectively. It is unknown whether the human immune system could tolerate
      invasion with a plant virus. To model such an alien virus invasion, we chose TMV
      (tobacco mosaic virus) and used human epithelial carcinoma cells (HeLa cells) as
      its 'fresh' host. We established a reliable system for transfecting TMV-RNA into
      HeLa cells and found that TMV-RNA triggered autophagy in HeLa cells as shown by
      the appearance of autophagic vacuoles, the conversion of LC3-I (light chain
      protein 3-I) to LC3-II, the up-regulated expression of Beclin1 and the
      accumulation of TMV protein on autophagosomal membranes. We observed suspected
      TMV virions in HeLa cells by TEM (transmission electron microscopy). Furthermore,
      we found that TMV-RNA was translated into CP (coat protein) in the ER
      (endoplasmic reticulum) and that TMV-positive RNA translocated from the cytoplasm
      to the nucleolus. Finally, we detected greatly increased expression of GRP78 (78
      kDa glucose-regulated protein), a typical marker of ERS (ER stress) and found
      that the formation of autophagosomes was closely related to the expanded ER
      membrane. Taken together, our data indicate that HeLa cells used ERS and ERS
      related autophagy to defend against TMV-RNA.

PMID- 21729007
TI  - Glycaemic variability affects ischaemia-induced angiogenesis in diabetic mice.
AB  - The aim of the present study was to investigate the role of GV (glycaemic
      variability) in diabetic vascular complications and to explore the molecular
      pathways modulated by glycaemic 'swings'. We developed a murine model. A total of
      30 diabetic mice received once daily basal insulin administration plus two oral
      boluses of glucose solution (GV group, named 'V') and 30 diabetic mice received
      once daily basal insulin plus two oral boluses of saline solution (stable
      hyperglycaemia group, named 'S') for a period of 30 days. Glycaemia was measured
      eight times daily to detect GV. Finally, postischaemic vascularization, induced
      by hindlimb ischaemia 30 days after diabetes onset, was evaluated. We found that
      GV was significantly different between S and V groups, whereas no significant
      difference in the mean glycaemic values was detected. Laser Doppler perfusion
      imaging and histological analyses revealed that the ischaemia-induced
      angiogenesis was significantly impaired in V mice compared with S group, after
      ischaemic injury. In addition, immunostaining and Western blot analyses revealed
      that impaired angiogenic response in V mice occurred in association with reduced
      VEGF (vascular endothelial growth factor) production and decreased eNOS
      (endothelial nitric oxide synthase) and Akt (also called protein kinase B)
      phosphorylation. In conclusion, we describe a murine model of GV. GV causes an
      impairment of ischaemia-induced angiogenesis in diabetes, likely to be
      independent of changes in average blood glucose levels, and this impaired
      collateral vessel formation is associated with an alteration of the VEGF pathway.

PMID- 21729008
TI  - A novel HLA-A allele detected by sequence-based typing: A*68:66.
AB  - The novel allele HLA-A*68:66 differs from HLA-A*68:01: 01:01 by a synonymous
      single nucleotide exchange at position 102 (C->T) and three non-synonymous
      exchanges at position 257 (G->A), position 259 (A->G) and position 261 (C->G) in
      exon 2.

PMID- 21729009
TI  - High positive antibody titers and adverse pregnancy outcome in women with
      antiphospholipid syndrome.
AB  - OBJECTIVE: To investigate whether in patients with antiphospholipid syndrome
      (APS), high positive antibody titers are associated with adverse pregnancy
      outcome. DESIGN: A retrospective cohort study of prospectively collected data.
      SETTING: Sheba Medical Center, Israel, a tertiary referral center. POPULATION
      SAMPLE: Pregnant women with APS. METHODS: Anticardiolipin, a-beta2-glycoprotein I
      antibodies, and lupus anticoagulant were measured before pregnancy. Women were
      divided into those with antibody titers >four times the upper limit of normal
      (high positive titer, HPT group), and the rest, into the positive titer (PT)
      group. All women were treated with daily enoxaparin and aspirin. MAIN OUTCOME
      MEASURES: Composite adverse fetal/neonatal outcome, defined as one or more of the
      following: fetal/neonatal loss, preterm birth <= 32 weeks, and birthweight below
      than 10th percentile. Composite adverse fetal/neonatal outcome was compared
      between the HPT and PT groups. Maternal adverse outcomes were also compared.
      RESULTS: 51 women with APS were followed during 55 pregnancies, 20 in the HPT and
      35 in the PT groups. The two groups were similar with regard to previous
      obstetric and clinical characteristics. Among HPT women, only 7/20 (35%)
      pregnancies culminated in appropriately grown, live-born infants >32 weeks'
      gestation, compared with 27/35 (77%) PT pregnancies. The risk of adverse
      fetal/neonatal outcome was 5.7 times higher (95%CI 1.9-17.7) for HPT than for PT
      women. CONCLUSIONS: Pregnant women with APS and high positive antiphospholipid
      antibody titers are a unique and extremely high risk group for adverse
      fetal/neonatal outcome. Stricter surveillance and possibly additional therapy
      options should be explored for this patient population.

PMID- 21729010
TI  - Novel HLA class I and II alleles identified during routine registry typing in
      2010.
AB  - Twenty-one novel human leukocyte antigen (HLA) class I and class II alleles are
      described: seven HLA-A alleles, five HLA-C alleles, five HLA-B alleles and four
      HLA-DRB1 alleles. Seventeen (~81%) of the 21 novel alleles are single nucleotide
      substitution variants when compared with their most homologous allele. Nine of
      these single nucleotide variants cause an amino acid substitution, while eight
      are silent substitutions. The remaining novel alleles differ from their most
      similar allele by two to three nucleotide substitutions. One novel HLA-C locus
      allele encodes an amino acid change at codon 10 that previously has not been
      reported to be polymorphic for this locus. Some of the new alleles encode novel
      codons and unique amino acid changes at polymorphic positions in the HLA-A
      (codons 24 and 156) and HLA-B (codons 40 and 115) loci.

PMID- 21729011
TI  - Inclusive altruism born of suffering: the relationship between adversity and
      prosocial attitudes and behavior toward disadvantaged outgroups.
AB  - This article reports the results of 2 studies examining altruism born of
      suffering (E. Staub & J. R. Vollhardt, 2008). More specifically, we examined
      inclusive altruism born of suffering, which is directed toward members of
      disadvantaged outgroups. Drawing on and integrating clinical and social
      psychological theories, we hypothesized that individuals who had suffered from
      adverse life events would be more likely to help the outgroups in need than those
      who had not suffered. This was demonstrated for helpers who had experienced
      various forms of suffering (interpersonal and group-based harm, natural
      disasters) and for 2 distinct types of prosocial behavior and attitudes (long
      term volunteering and disaster aid) benefiting outgroups within society and from
      other countries. We also found that prosocial attitudes toward tsunami victims
      were highest among those who had suffered in a similar way (from natural
      disasters). Additionally, we examined the underlying social psychological
      processes and found that empathy and reduced ingroup bias (but not personal
      distress) mediated the effect (Study 2). Implications for social justice and an
      empowering view of victims as potential helpers in society are discussed.

PMID- 21729012
TI  - Nuke the nanny state: a dream of life in the bad old days.

PMID- 21729013
TI  - Who are the fathers in Healthy Families Arizona? An examination of father data in
      at-risk families.
AB  - Despite substantial research documenting the importance of father-child
      relations, little is known about fathers in families considered at risk for child
      abuse, and this lack of information makes adequate targeting of fathers in
      interventions challenging. This research aims to provide information that will
      aid interventions in targeting fathers and addressing father-related family
      issues through: (a) providing descriptive information regarding fathers in
      families at risk for child abuse, and (b) examining aspects of family well-being
      relative to father involvement. Analyses were conducted on mother-report data in
      families eligible for the Healthy Families Arizona prevention program (N = 197).
      Results indicated that although only 15% of parents in the sample were married,
      47% of families had resident fathers, and 77% of fathers had some contact with
      their new babies. Families with greater father involvement had better prenatal
      care, higher incomes, less maternal involvement in Child Protective Services,
      less physical domestic violence (DV), and greater maternal mental health
      reflected through less loneliness. These findings have implications for targeting
      nonresident as well as resident fathers in families at risk for child abuse and
      for exploring DV issues in families with noninvolved fathers.

PMID- 21729014
TI  - Bringing baby home together: examining the impact of a couple-focused
      intervention on the dynamics within family play.
AB  - The transition to parenthood brings with it challenges to a couple's
      relationship, which in turn are likely to negatively impact coparenting and
      overall family process. The focus of the current study was to examine the effects
      of the Bringing Baby Home psycho-educational intervention at the first
      postintervention follow-up for promoting positive coparenting and family process
      within the mother-father-baby family system. Expectant parents (N = 181) were
      recruited from the greater Seattle area to participate in a longitudinal random
      clinical trials study. Families were randomly assigned to a control, workshop, or
      workshop plus support group. Observational coding indexed both parent and baby
      contribution to family interaction during the Lausanne Triadic Play procedure.
      Principal components analysis was used to create summary factors describing the
      family play. Results of intent-to-treat analyses indicated that the Bringing Baby
      Home program was successful in promoting less competition during family play.
      There also was an effect of workshop timing, suggesting that fathers who took the
      workshop prebirth were less likely to exhibit intrusiveness during mother-baby
      focused play than those who received it postbirth. Implications for promoting the
      formation of positive family-level relations are discussed.

PMID- 21729015
TI  - Peer interventions to promote health: conceptual considerations.
AB  - Peers have intervened to promote health since ancient times, yet few attempts
      have been made to describe theoretically their role and their interventions.
      After a brief overview of the history and variety of peer-based health
      interventions, a 4-part definition of peer interveners is presented here with a
      consideration of the dimensions of their involvement in health promotion. Then, a
      2-step process is proposed as a means of conceptualizing peer interventions to
      promote health. Step 1 involves establishing a theoretical framework for the
      intervention's main focus (i.e., education, social support, social norms, self
      efficacy, and patient advocacy), and Step 2 involves identifying a theory that
      justifies the use of peers and might explain their impact. As examples, the
      following might be referred to: theoretical perspectives from the mutual support
      group and self-help literature, social cognitive and social learning theories,
      the social support literature, social comparison theory, social network
      approaches, and empowerment models.

PMID- 21729016
TI  - An epidemiological examination of parenting and family correlates of emotional
      problems in young children.
AB  - The present article used data from a community sample of primary caregivers of
      children between 4 and 7 years old to investigate the prevalence and correlates
      of emotional symptoms in young children transitioning to elementary school.
      Mothers (n = 3,483) and fathers (n = 1,019) living in metropolitan areas of
      eastern Australia participated in a telephone survey of parenting practices and
      child behavioral and emotional problems. Fifteen percent of mothers and 12% of
      fathers reported that their child showed clinically elevated levels of emotional
      symptoms. The most common parental responses to a child's anxious or distressed
      behavior were to use physical contact, talk in a soothing voice, or encourage
      their child to be brave, while fewer than 10% of parents ignored their child's
      distress by not giving any attention. For mothers, reports of child emotional
      symptoms were associated with mothers' use of physical contact to soothe their
      children, mothers' level of personal stress and depression, their confidence in
      managing anxious or distressed behavior, and consistency in their application of
      discipline. Fathers' encouragement of their children to be brave and fathers'
      confidence in managing anxious or distressed behavior were associated with
      reduced child emotional symptoms. These findings have implications for the
      development of universal prevention programs for internalizing disorders in
      children.

PMID- 21729017
TI  - Construction of court petitions in cases of alternative placement of children at
      risk: meaning-making strategies that social workers use to shape court decisions.
AB  - This study examines court petitions constructed by 19 Israeli social workers in
      cases involving the placement of 37 maltreated children in alternative care. The
      petition is seen not as a systemic description of the child made by the social
      worker, but rather as a construction based on the social workers' understandings
      and interpretations with the aim of shaping court decisions. As such, the article
      describes a number of meaning-making strategies that social workers employ to
      construct petitions: (a) constructing the mother as "the problem," (b)
      constructing the story as one of "no change in sight," (c) constructing out-of
      home care as the only solution, with no other alternatives, and (d) minimizing
      the narrator's personal involvement in the case. Implications for child
      protection officers are presented.

PMID- 21729018
TI  - Psychosocial consequences of caregiver transitions for maltreated youth entering
      foster care: the moderating impact of community violence exposure.
AB  - Youth who experience a greater number of caregiver transitions during childhood
      are at risk for developing a host of psychosocial problems. Although researchers
      have examined individual-level factors that may moderate this association, no
      known studies have examined the impact of community-level factors. The current
      study investigated whether community violence exposure (CVE) moderated the
      association between number of prior caregiver transitions and increases in levels
      of externalizing and internalizing problems for a sample of youth entering foster
      care. Participants included 156 youth (aged 9-11 at first assessment) removed
      from their homes because of maltreatment. Youth provided reports of caregiver
      transitions and CVE at baseline, and caregivers, teachers, and youth reported on
      externalizing and internalizing problems 18-22 months later. Results from
      hierarchical multiple regression analyses indicated that youth with a greater
      number of caregiver transitions and higher levels of CVE evidenced significant
      increases in levels of psychosocial problems. The results of the study are
      discussed in terms of their implications for child welfare services.

PMID- 21729019
TI  - Conceptualizing housing careers for vulnerable youth: implications for research
      and policy.
AB  - Research on the experiences of youth leaving foster care as they enter adulthood
      has identified their risk for homelessness and housing instability. Although this
      finding has been consistent, it has not received sufficient empirical or
      conceptual attention. In this article, we (a) review the recent findings on
      housing outcomes for former foster youth; (b) identify relevant theoretical
      frameworks to examine housing outcomes for these youth, with specific attention
      to the concept of housing career; (c) describe existing policy; and (d) propose
      further strategies for understanding and, therefore, influencing outcomes for
      this population. Based on this analysis, we conclude with implications for
      policy, practice, and further research to assist these young people.

PMID- 21729020
TI  - Correlates of street-survival behaviors in homeless young adults in four U.S.
      cities.
AB  - This study assessed the prevalence and correlates of behaviors used by homeless
      young people to survive on the streets. Survival behaviors include prostitution,
      selling blood or plasma, dealing drugs, stealing, and panhandling. One hundred
      ninety-six homeless young adults from 4 metropolitan areas-Los Angeles, CA (n =
      50); Austin, TX (n = 50); Denver, CO (n = 50); and St. Louis, MO (n = 46)
      participated in individual, semistructured, face-to-face interviews. Researchers
      predicted that youth transience would be related to high rates of survival
      behaviors. Multivariate logistic regression was used to test a model predicting
      relationships between survival behaviors and transience, employment, substance
      use, and social support. Young adults who were transient, unemployed, drug
      addicted, and reliant on peers for help were more likely to use these survival
      behaviors. In addition, among the transient subsample, being White, more reliant
      on peers for help, more transient, and having been victimized were associated
      with high use of these survival behaviors. Identification of the environmental
      and demographic factors associated with survival behaviors suggests that there
      may be value in combining harm-reduction strategies with efforts to reduce the
      transience of homeless young adults.

PMID- 21729021
TI  - Effects of out-of-home mental health treatment on probability of criminal charge
      during the transition to adulthood.
AB  - Criminal justice-related outcomes for youth who have been served in out-of-home
      mental health settings such as residential treatment and inpatient
      hospitalization are unclear. This study longitudinally modeled the changing
      probability of being charged with a crime from age 16 to 25, including being
      served in out-of-home treatment and aging into adulthood, while controlling for
      person-level covariates such as gender, race, past criminal charges, and mental
      health diagnoses. Results indicated that out-of-home treatment was related to a
      decreased probability of being charged with a crime during treatment. However,
      the preventive effect was small; estimates indicated only one criminal charge
      avoided for every 4 years of out-of-home treatment. Out-of-home treatment had no
      relationship to posttreatment probability of charge. Other significant
      contributors to being charged included gender, a substance use diagnosis, and an
      offense record prior to age 16. Evidence indicated that out-of-home treatment was
      used as an alternative to detention and incarceration for both juveniles and
      adults.

PMID- 21729022
TI  - Patterns of mental health, substance abuse, and justice system involvement among
      youth aging out of child welfare.
AB  - Although research on youth aging out of the child welfare system has increased,
      there has been limited focus on how their experiences vary. In particular, there
      is a need to examine patterns in the involvement of these youth in other systems,
      which indicate constellations of challenges facing these young people as they
      transition out of care and into adulthood. Using administrative data from a large
      birth cohort of individuals born between 1985 and 1994 whose families have been
      involved in the child welfare system, this article presents an analysis of the
      mental health, substance abuse, juvenile justice, and criminal justice system
      involvement of youth who have aged out of child welfare. Using a 2-step cluster
      analysis, we identify 5 subgroups of youth. Two of these groups, accounting for
      almost half of the youth, have little other system involvement and have child
      welfare care careers of relative stability. The other 3 groups, consisting of
      just over half of the youth, have much more extensive other system involvement,
      as well as care careers marked by instability and a greater proportion of time
      spent in congregate care.

PMID- 21729023
TI  - Increased immunoreactivity of membrane type-1 matrix metalloproteinase (MT1-MMP)
      and beta-catenin in high-risk basal cell carcinoma.
AB  - BACKGROUND: Although various immunohistological markers have been investigated to
      assess the aggressive characteristics of basal cell carcinoma (BCC), the role of
      membrane type-1 matrix metalloproteinase (MT1-MMP) has not been well established.
      OBJECTIVES: To clarify the precise role of MT1-MMP in BCC, MT1-MMP expression was
      studied in various histological subtypes of BCC. MATERIALS AND METHODS: High-risk
      subtypes of BCC were compared by assessing the expression of beta-catenin and MT1
      MMP. The tissue microarray technique was used for immunohistochemical staining.
      Fifty-eight samples were divided into six subtypes (10 nodular, 12 mixed, nine
      infiltrative, eight morphoeiform, 10 micro-nodular and nine basosquamous).
      Overall, the 10 nodular BCC samples were classified as low-risk BCC and the
      remaining 48 samples were classified as high-risk BCCs. RESULTS: beta-Catenin
      immunoreactivity was increased in the high-risk BCCs compared with the low-risk
      (nodular) BCC (P < 0.001). Nuclear beta-catenin immunoreactivity was increased at
      the invading front of mixed BCC tumour islands compared with the upper portion of
      the lesion (P < 0.01). For the mixed BCC (P < 0.01), infiltrative BCC (P <
      0.001), morphoeiform BCC (P < 0.001), micronodular BCC (P < 0.001) and
      basosquamous (P < 0.001) carcinoma, beta-catenin immunoreactivity was increased
      at the invading front compared with nodular BCC. MT1-MMP immunoreactivity was
      increased in the high-risk BCCs compared with the low-risk (nodular) BCC (P <
      0.01). The membranous MT1-MMP immunoreactivity was increased at the invading
      front of mixed BCC tumour islands compared with the upper portion of the lesions
      (P < 0.01). For the mixed (P < 0.01), infiltrative (P < 0.05), morphoeiform (P <
      0.05), micronodular (P > 0.05) and basosquamous (P < 0.05) BCC, MT1-MMP
      immunoreactivity was also increased at the invading front compared with nodular
      BCC. CONCLUSIONS: The results of this study suggest that MT1-MMP might be a novel
      marker for high-risk BCC. In addition, expression of both beta-catenin and MT1
      MMP was increased in high-risk BCC tumour cells, indicating that these two
      proteins may play an important role in locally invasive and highly destructive
      growth behaviour of high-risk BCCs.

PMID- 21729025
TI  - Formation of immunoglobulin light chain amyloid oligomers in primary cutaneous
      nodular amyloidosis.
AB  - BACKGROUND: Primary cutaneous nodular amyloidosis (PCNA) is thought to be a
      plasma cell dyscrasia. The amyloid deposits are found in the dermis and subcutis,
      and they contain clonal immunoglobulin light chains, produced by a local
      proliferation of plasma cells. New insights into amyloid diseases have revealed
      that the pathology is due more to the presence of small, misfolded protein
      species termed oligomers than to the deposition of fibrillar material.
      OBJECTIVES: To demonstrate the presence of amyloid oligomers in PCNA and to
      provide evidence that cutaneous amyloid diseases share a common pathogenic
      pathway similar to other amyloid diseases. METHODS: Immunohistochemical staining
      with conformation-specific and sequence-specific antibodies was used to localize
      different amyloid species of light chain immunoglobulins in a case of PCNA.
      Additionally, in vitro characterization of immunoglobulin oligomers and fibrils
      was performed to determine, through toxicity studies in a human keratinocyte cell
      line, which amyloidogenic form of the immunoglobulin is toxic in PCNA. RESULTS:
      Amyloid oligomers were identified in PCNA. Oligomers were mainly formed by lambda
      light chain immunoglobulins, and kappa light chain oligomers were detected in
      lesser amounts. Amyloid species were detected intra- and extracellularly. In
      addition, amyloid oligomers and fibrils, derived from unknown protein sources,
      were detected. This finding suggests that immunoglobulin amyloids can act as
      seeds capable of inducing the aggregation of heterogeneous proteins in the skin.
      Furthermore, cytotoxicity studies demonstrated that immunoglobulin oligomers, but
      not monomers or fibrils, are toxic to human keratinocytes. CONCLUSIONS: These
      data indicate that PCNA has common pathways with other amyloid diseases with
      respect to protein misfolding and pathogenesis. Immunoglobulin oligomers may
      prove to be targets for the treatment of PCNA.

PMID- 21729024
TI  - Roles of the immune system in skin cancer.
AB  - Over the past several decades, there has been increasing interest in
      understanding the roles of the immune system in the development and progression
      of cancer. The importance of the immune system in human skin cancer has been long
      recognized based primarily upon the increased incidence of skin cancers in organ
      transplant recipients and mechanisms of ultraviolet (UV) radiation-mediated
      immunomodulation. In this review, we integrate multiple lines of evidence
      highlighting the roles of the immune system in skin cancer. First, we discuss the
      concepts of cancer immunosurveillance and immunoediting as they might relate to
      human skin cancers. We then describe the clinical and molecular mechanisms of
      skin cancer development and progression in the contexts of therapeutic
      immunosuppression in organ transplant recipients, viral oncogenesis, and UV
      radiation-induced immunomodulation with a primary focus on basal cell carcinoma
      and squamous cell carcinoma. The clinical evidence supporting expanding roles for
      immunotherapy is also described. Finally, we discuss recent research examining
      the functions of particular immune cell subsets in skin cancer and how they might
      contribute to both antitumour and protumour effects. A better understanding of
      the biological mechanisms of cancer immunosurveillance holds the promise of
      enabling better therapies.

PMID- 21729026
TI  - Teledermatology applied following patient selection by general practitioners in
      daily practice improves efficiency and quality of care at lower cost.
AB  - BACKGROUND: Teledermatology, the application of telemedicine in the field of
      dermatology, has similar accuracy and reliability as physical dermatology.
      Teledermatology has been widely used in daily practice in the Netherlands since
      2005 and is fully reimbursed. OBJECTIVES: This study prospectively investigated
      the effect of teledermatology on efficiency, quality and costs of care when
      integrated in daily practice and applied following patient selection by the
      general practitioner (GP). METHODS: Teledermatology consultations between GP and
      regional dermatologist were performed in daily GP practice in the Netherlands.
      Efficiency of care was measured by the decrease in the number of physical
      referrals to the dermatologist. Quality of care was measured by the percentage of
      teleconsultations for second opinion, physical referrals resulting from these
      teleconsultations, the response time of the dermatologists and educational effect
      experienced by the GP. Costs of conventional healthcare without teledermatology
      were compared with costs with teledermatology. RESULTS: One thousand, eight
      hundred and twenty GPs and 166 dermatologists performed teledermatology, and
      37,207 teleconsultations performed from March 2007 to September 2010 were
      included. In the group of patients where the GP used teleconsultation to prevent
      a referral (n =26,596), 74% of physical referrals were prevented. In the group of
      patients where the GP used teleconsultation for a second opinion (n =10,611), 16%
      were physically referred after teleconsultation. The prevented referral rate in
      the total population was 68%. The mean response time of dermatologists was 4.6 h
      (median 2.0). GPs indicated that there was a beneficial educational effect in 85%
      of the teleconsultations. The estimated cost reduction was 18%. CONCLUSIONS:
      Teledermatology can lead to efficient care probably at lower cost. We are
      therefore of the opinion that teledermatology following GP selection should be
      considered as a possible pathway of referral to secondary care.

PMID- 21729027
TI  - Short- and medium-term efficacy of specific hydrotherapy in inherited ichthyosis.
AB  - BACKGROUND: Management of inherited ichthyoses is symptomatic. Despite treatment,
      skin symptoms have a major impact on patients' quality of life (QoL). OBJECTIVES:
      To assess the short- and medium-term efficacy of hydrotherapy on QoL and clinical
      symptoms of patients with inherited ichthyosis. METHODS: In this 9-month
      prospective, open-label, multicentre study, 20 children and 24 adults with
      ichthyosis were enrolled in several French reference and competence centres, 2
      months before undergoing a 3-week treatment with specific hydrotherapeutic
      management at Avene Hydrotherapy Centre. At baseline (2 months before
      hydrotherapy), beginning (D0) and end of hydrotherapy (D18), and 3 and 6 months
      later at the reference and competence centres, patients self-assessed QoL using
      the Dermatology Life Quality Index (DLQI) or its paediatric version (Children's
      DLQI), and investigators evaluated ichthyosis severity using a specific clinical
      ichthyosis score. RESULTS: The DLQI scores were significantly improved not only
      at the end of the hydrotherapy treatment (-56% vs. baseline; mean +/- SD 3.59 +/-
      4.30 at D18 vs. 8.35 +/- 5.71 at D0; P < 0.0001), but also at 3 months (-28% vs.
      baseline; P = 0.01) and 6 months after hydrotherapy (-26% vs. baseline; mean +/-
      SD 5.21 +/- 5.11 vs. 6.89 +/- 5.38; P = 0.03) (primary criterion). Clinical
      symptoms were also significantly improved at all post-treatment visits, with a
      decrease of the mean clinical ichthyosis score by -38% between D0 and D18, by 
      30% at 3 months and by -31% at 6 months vs. baseline. CONCLUSIONS: A 3-week
      treatment at Avene Hydrotherapy Centre provided significant and persisting
      improvement of QoL and clinical symptoms in patients with inherited ichthyoses.

PMID- 21729028
TI  - Iatrogenic androgenetic alopecia in a male phenotype 46XX true hermaphrodite.

PMID- 21729029
TI  - Phenotypic analysis in a case of hydroa vacciniforme-like eruptions associated
      with chronic active Epstein-Barr virus disease of gammadelta T cells.

PMID- 21729030
TI  - Evidence-based (S3) guideline on topical corticosteroids in pregnancy.
AB  - Women with skin conditions may need topical corticosteroids during pregnancy.
      However, little is known about the effects of topical corticosteroids on the
      fetus. A guideline subcommittee of the European Dermatology Forum was organized
      to develop an evidence-based guideline on the use of topical corticosteroids in
      pregnancy (http://www.euroderm.org/edf/images/stories/guidelines/EDF-Guideline-on
      Steroids-in-Pregnancy.pdf). The evidence from a Cochrane Review suggested that
      the major possible adverse effects on the fetus of topical corticosteroids were
      orofacial clefts when used preconceptionally and in the first trimester of
      pregnancy, and fetal growth restriction when very potent topical corticosteroids
      were used during pregnancy. To obtain robust evidence, a large population-based
      cohort study (on 84,133 pregnant women from the U.K. General Practice Research
      Database) was performed, which found a significant association of fetal growth
      restriction with maternal exposure to potent/very potent topical corticosteroids,
      but not with mild/moderate topical corticosteroids. No associations of maternal
      exposure to topical corticosteroids of any potency with orofacial cleft, preterm
      delivery and fetal death were found. Moreover, another recent Danish cohort study
      did not support a causal association between topical corticosteroid and orofacial
      cleft. The current best evidence suggests that mild/moderate topical
      corticosteroids are preferred to potent/very potent ones in pregnancy, because of
      the associated risk of fetal growth restriction with the latter.

PMID- 21729031
TI  - Brain-derived nerve factor and neurotrophins in androgenetic alopecia.
AB  - BACKGROUND: Several growth factors and cytokines have been shown to be involved
      in normal hair cycling as well as in androgenetic alopecia (AGA). However, the
      molecular cascades in AGA downstream from androgen receptor activation are far
      from being fully elucidated. OBJECTIVES: We sought to determine the difference in
      the protein expression of growth factors/cytokines in balding vs. nonbalding
      scalp specimens from the same individuals affected with AGA. METHODS: Balding and
      nonbalding scalp specimens were collected from four men with pattern baldness.
      Dermal papilla (DP) cells were isolated and cultured. Quantifying the protein
      expression of growth factors and cytokines expressed by these cells was performed
      using Quantibody(r) Human Growth Factor Array-1 (RayBiotech, Inc., Norcross, GA,
      U.S.A.). RESULTS: Brain-derived nerve factor (BDNF) protein expression was
      upregulated by approximately 12-fold in supernatants obtained from balding as
      compared with nonbalding DP cells (P < 0.001). Expression of neurotrophin-3 and
      of beta-nerve growth factor was also upregulated. On the other hand, protein
      expression of insulin-like growth factor-1 and its binding proteins as well as of
      the vascular endothelial growth factor family were significantly downregulated in
      the balding scalp. CONCLUSIONS: Neurotrophic factors, especially BDNF, may be
      important in mediating the effects of androgens on hair follicles, serving as a
      negative regulatory control signal. Further studies may lead to novel
      pharmacological interventions in AGA.

PMID- 21729032
TI  - Mild staphylococcal scalded skin syndrome: an underdiagnosed clinical disorder.

PMID- 21729033
TI  - Novel adenosine triphosphate (ATP)-binding cassette, subfamily A, member 12
      (ABCA12) mutations associated with congenital ichthyosiform erythroderma.

PMID- 21729034
TI  - Patterns of bone mineral acquisition in children with epidermolysis bullosa: a
      longitudinal study.
AB  - BACKGROUND: Reduced bone mass and fractures are known complications of
      generalized forms of epidermolysis bullosa (EB). However, the aetiology -
      inadequate bone acquisition, premature bone loss, or a combination - is unclear.
      OBJECTIVES: To determine patterns of bone mineral acquisition in children with EB
      and to identify clinical and laboratory correlates of change in areal bone
      mineral density (aBMD). METHODS: Seventeen subjects >= 6 years of age with
      generalized EB were studied at two visits at least 12 months apart with clinical
      and laboratory evaluations and dual energy X-ray absorptiometry scans of the
      lumbar spine. Wilcoxon signed-rank tests were used to determine if changes from
      baseline to follow-up were significant. Wilcoxon rank-sum tests were used to
      compare subjects with gains in aBMD Z-score with those who experienced no change
      or decreases to determine if baseline laboratory or clinical characteristics
      differed between the two groups. RESULTS: Subjects gained height and weight at
      follow-up, but there was no significant improvement in mean Z-scores for height,
      weight or body mass index. Laboratory values did not change significantly. Mean
      bone mineral content and aBMD of the lumbar spine increased significantly at
      follow-up, but mean aBMD Z-scores remained static. No differences in clinical
      characteristics or laboratory values were seen between subjects with increased
      aBMD Z-scores vs. those whose scores decreased or did not change. CONCLUSIONS:
      Low bone mass in children with generalized EB is due primarily to inadequate
      gains in aBMD. Interventions to improve overall health and to help build bone
      mass in this patient population are warranted.

PMID- 21729035
TI  - Jeavons syndrome existing as occipital cortex initiating generalized epilepsy.
AB  - PURPOSE: Jeavons syndrome (JS) is one of the underreported epileptic syndromes
      characterized by eyelid myoclonia (EM), eye closure-induced
      seizures/electroencephalography (EEG) paroxysms, and photosensitivity. JS has
      been proposed as idiopathic generalized epilepsy (IGE) because of normal
      posterior dominant background activity and paroxysmal generalized ictal
      epileptiform discharges (EDs). However, we noticed subtle occipital EDs preceding
      EM and interictal posterior EDs using digital video-EEG. We studied clinical and
      EEG findings in JS to determine the specific occipital lobe relation to this "eye
      closure-induced" reflex IGE. METHODS: We identified 12 children who met the
      diagnostic criteria of JS from January 2004 to April 2009 at the Hospital for
      Sick Children, Toronto, Canada. All patients had EM captured by video-EEG. We
      reviewed and described ictal EEG patterns, interictal abnormalities, and
      demographics, clinical, and neuroimaging findings. KEY FINDINGS: All patients but
      one were female (92%). Age at seizure onset ranged from 1.5 to 9 years, with a
      mean age of 4.9 years. Six patients (50%) were previously diagnosed as having
      absence epilepsy and 10 patients were on antiepileptic medications. All 12
      patients had normal posterior dominant alpha rhythm, reactive to eye opening and
      closure. Spiky posterior alpha activity was noted with sustained eye closure in
      six patients (50%). Interictally, there were generalized EDs found in 10 patients
      (83%); four of them also had focal interictal EDs over the posterior head region.
      Eleven patients (92%) had evidence of focal posterior ictal EDs. EM and/or
      paroxysmal EDs were induced by photic stimulation in 9 (75%) and hyperventilation
      in 7 (58%). SIGNIFICANCE: We observed two neurophysiologic findings in JS: (1)
      focal interictal EDs from posterior head region; and (2) predominant focal
      posterior ictal EDs preceding generalized EDs. Further clinical observations of
      seizures induced by eye closure, photic stimulation, and hyperventilation along
      with EEG paroxysms would raise the possibility of the occipital cortex initiating
      generalized epilepsy network involving the brainstem, and thalamocortical and
      transcortical pathways in JS.

PMID- 21729036
TI  - Clinical comparability of the new antiepileptic drugs in refractory partial
      epilepsy: a systematic review and meta-analysis.
AB  - PURPOSE: Evaluate the clinical comparability of new antiepileptic drugs (AEDs) in
      partial refractory epilepsy. METHODS: Systematic review of randomized trials
      (RCTs) comparing a new AED (add-on treatment) with placebo or another AED.
      PRIMARY OUTCOMES: responder (>=50% seizure reduction) and withdrawal
      (tolerability) rates. Pooled estimates of odds ratios (ORs) and number needed
      treat/harm (NNT/NNH) taking into account baseline risk were derived by random
      effects meta-analysis. Adjusted frequentist indirect comparisons between AEDs
      were estimated. KEY FINDINGS: Sixty-two placebo-controlled (12,902 patients) and
      eight head-to-head RCTs (1,370 patients) were included. Pooled ORs for responder
      and withdrawal rates (vs. placebo) were 3.00 [95% confidence interval (CI) 2.63
      3.41] and 1.48 (1.30-1.68), respectively. Indirect comparisons of responder rate
      based on relative measurements of treatment effect (ORs) favored topiramate
      (1.52; 1.06-2.20) in comparison to all other AEDs, whereas gabapentin (0.67; 0.46
      0.97) and lacosamide (0.66; 0.48-0.92) were less efficacious, without significant
      heterogeneity. When analyses were based on absolute estimates (NNTs), topiramate
      and levetiracetam were more efficacious, whereas gabapentin and tiagabine were
      less efficacious. Withdrawal rate was higher with oxcarbazepine (OR 1.60; 1.12
      2.29) and topiramate (OR 1.68; 1.07-2.63), and lower with gabapentin (OR 0.65;
      0.42-1.00) and levetiracetam (OR 0.62; 0.43-0.89). SIGNIFICANCE: The differences
      found are of relatively small magnitude to allow a definitive conclusion about
      which new AED(s) has superior effectiveness. This uncertainty probably reflects
      the limitations of conclusions based on indirect evidence. The process of
      pharmacologic clinical decision making in partial refractory epilepsy probably
      depends more on other aspects, such as individual patient characteristics and
      pharmacoeconomics, than on available controlled randomized evidence.

PMID- 21729037
TI  - Long-term control of epileptic drop attacks with the combination of valproate,
      lamotrigine, and a benzodiazepine: a 'proof of concept,' open label study.
AB  - PURPOSE: Long-term medical management of epileptic drop attacks is usually
      unsatisfactory and more effective antiepileptic drug (AED) regimens are needed.
      The present study aimed at providing proof of concept that previously refractory
      epileptic drop attacks could be significantly and safely controlled by the
      specific combination of valproate, lamotrigine, and a benzodiazepine. METHODS: An
      open label trial providing class IV evidence of efficacy, including 32 patients
      with cryptogenic/symptomatic, generalized or multifocal epilepsies, and
      refractory drop attacks. Following baseline, the combination under study was
      introduced and patients followed for 12 months. Frequency of drop attacks was
      compared at 3-month intervals with that during baseline and correlated with
      clinical, electroencephalography (EEG), and imaging variables. A list of putative
      side effects was read to patients and caregivers at each visit. KEY FINDINGS:
      Four patients were excluded, one due to a Stevens-Johnson syndrome (SJS). Median
      number of drop attacks decreased 96% between baseline and the fourth trimester of
      the study (from 50 to 2; p<0,001). Intention-to-treat (ITT) analysis showed that
      15 patients (47%) had complete control, 7 (21%) had a 75% and 5 (15%) had a 50
      74% reduction in the frequency of falls in the fourth trimester. Twenty-two
      patients (68%) had side effects, but except for the three excluded because of
      early rash, caregivers did not consider discontinuation. Mean final dose of
      valproate was 35.9 mg/kg/day and that of lamotrigine 4.9 mg/kg/day. Twenty
      patients used clobazam, eight nitrazepam, and the other four clonazepam as the
      elected benzodiazepine. Outcome did not correlate with clinical, EEG, and imaging
      variables. SIGNIFICANCE: This open label study suggests that the combination of
      valproate, lamotrigine, and a benzodiazepine can markedly reduce the frequency of
      epileptic drop attacks in patients with generalized or multifocal epilepsies.
      Careful clinical monitoring for early signs of SJS is needed.

PMID- 21729038
TI  - Effect of intracranial administration of ethosuximide in rats with spontaneous or
      pentylenetetrazol-induced spike-wave discharges.
AB  - PURPOSE: Generalized absence seizures are characterized by bilateral spike-wave
      discharges (SWDs), particularly in the frontoparietal cortical region. In WAG/Rij
      and GAERS rats with absence epilepsy, recent evidence indicates that SWDs arise
      first from the lateral somatosensory cortex (LSC), that is, the cortical focus
      theory. To further understand the cortical role in SWD generation, two epileptic
      rat models were assessed. METHODS: Two models, Long-Evans rats with spontaneous
      SWDs and Wistar rats with low-dose pentylenetetrazol-induced SWDs (20 mg/kg,
      i.p.), were administered intracortical or intrathalamic ethosuximide (ESM) or
      saline. Electroencephalographic recordings were analyzed before and after
      intracranial microinfusion to evaluate onset, frequency, and duration of SWDs.
      KEY FINDINGS: In both epileptic rat models, ESM in the LSC significantly reduced
      SWD number, shortened SWD duration, and delayed SWD onset compared to saline. By
      contrast, ESM in the medial somatosensory cortex had little effect compared to
      saline. Intrathalamic infusion of ESM only delayed SWD onset. SIGNIFICANCE: These
      findings suggest that the LSC may be essential for the occurrence of SWDs. Our
      data support the cortical focus theory for the generation of absence seizures.

PMID- 21729039
TI  - Atorvastatin treatment during epileptogenesis in a rat model for temporal lobe
      epilepsy.
AB  - PURPOSE: It has been shown that blood-brain barrier leakage together with
      inflammation could contribute to epileptogenesis and seizure progression in a rat
      model for temporal lobe epilepsy. Because statins have been shown to reduce blood
      brain barrier permeability and inflammation in neurological diseases, we aimed to
      restore the integrity of the blood-brain barrier in epileptic rats using
      atorvastatin. If this drug could restore the blood-brain barrier, a reduction of
      brain inflammation might be expected, thereby delaying or preventing the
      development of epilepsy. METHODS: Rats were orally treated with atorvastatin
      (once daily, 10 mg/kg) or vehicle for 14 days, starting 7 days before the
      induction of epilepsy (which was evoked by electrical stimulation of the angular
      bundle until rats developed status epilepticus). Seizure activity was monitored
      continuously until 6 weeks after status epilepticus using video-EEG
      (electroencephalography). Fluorescein was administered at this time point to
      quantify blood-brain barrier leakage. Brain inflammation, neuronal death, and
      synaptic reorganization were assessed by (immuno)histologic stainings. KEY
      FINDINGS: Atorvastatin treatment did not affect the duration of status
      epilepticus or the development of epilepsy. At 6 weeks after status epilepticus,
      blood-brain barrier leakage was evident both in atorvastatin-treated and vehicle
      treated rats in limbic brain regions (hippocampus, entorhinal cortex, piriform
      cortex). Atorvastatin treatment had not reduced inflammation, neuronal death, or
      synaptic reorganization. SIGNIFICANCE: The lack of any favorable effect of
      atorvastatin on the restoration of the blood-brain barrier, cell death, or brain
      inflammation suggests that atorvastatin is more effective in neurological
      diseases where the adaptive immune response plays a crucial role and less so in a
      disease as temporal lobe epilepsy, where the innate immune response is more
      prominent.

PMID- 21729040
TI  - Endothelial dysfunction: a critical determinant in inflammation-associated
      adrenal insufficiency?

PMID- 21729041
TI  - Convergence, adaptation, and constraint.
AB  - Convergent evolution of similar phenotypic features in similar environmental
      contexts has long been taken as evidence of adaptation. Nonetheless, recent
      conceptual and empirical developments in many fields have led to a proliferation
      of ideas about the relationship between convergence and adaptation. Despite
      criticism from some systematically minded biologists, I reaffirm that convergence
      in taxa occupying similar selective environments often is the result of natural
      selection. However, convergent evolution of a trait in a particular environment
      can occur for reasons other than selection on that trait in that environment, and
      species can respond to similar selective pressures by evolving nonconvergent
      adaptations. For these reasons, studies of convergence should be coupled with
      other methods-such as direct measurements of selection or investigations of the
      functional correlates of trait evolution-to test hypotheses of adaptation. The
      independent acquisition of similar phenotypes by the same genetic or
      developmental pathway has been suggested as evidence of constraints on
      adaptation, a view widely repeated as genomic studies have documented phenotypic
      convergence resulting from change in the same genes, sometimes even by the same
      mutation. Contrary to some claims, convergence by changes in the same genes is
      not necessarily evidence of constraint, but rather suggests hypotheses that can
      test the relative roles of constraint and selection in directing phenotypic
      evolution.

PMID- 21729042
TI  - Neutral biodiversity theory can explain the imbalance of phylogenetic trees but
      not the tempo of their diversification.
AB  - Numerous evolutionary studies have sought to explain the distribution of
      diversity across the limbs of the tree of life. At the same time, ecological
      studies have sought to explain differences in diversity and relative abundance
      within and among ecological communities. Traditionally, these patterns have been
      considered separately, but models that consider processes operating at the level
      of individuals, such as neutral biodiversity theory (NBT), can provide a link
      between them. Here, we compare evolutionary dynamics across a suite of NBT
      models. We show that NBT can yield phylogenetic tree topologies with imbalance
      closely resembling empirical observations. In general, metacommunities that
      exhibit greater disparity in abundance are characterized by more imbalanced
      phylogenetic trees. However, NBT fails to capture the tempo of diversification as
      represented by the distribution of branching events through time. We suggest that
      population-level processes might therefore help explain the asymmetry of
      phylogenetic trees, but that tree shape might mislead estimates of evolutionary
      rates unless the diversification process is modeled explicitly.

PMID- 21729043
TI  - The impact of gene-tree/species-tree discordance on diversification-rate
      estimation.
AB  - Molecular phylogenies are often used to test hypotheses about the tempo and mode
      of speciation and extinction. One commonly used statistic is Pybus and Harvey's
      gamma, which measures the density of ordered internode distances on an
      ultrametric tree to infer earlier (negative gamma) or later (positive gamma)
      bursts of diversification. However, coalescent theory predicts that gamma might
      be biased toward negative values (inferring early bursts of diversification) when
      using gene trees rather than species trees. Gene divergences predate species
      divergences, increasingly so at higher effective population sizes (N(e)), and
      proportionally more so toward the tips of the tree. Thus, gene trees will have a
      higher density of older nodes in many cases (particularly at higher N(e)), due to
      the disproportionate lengthening of terminal branches. This will yield an
      artifactual signature of early bursts of diversification when estimating gamma
      from gene trees. We simulate gene trees within species trees under both Yule
      (pure-birth) and birth-death processes, and demonstrate support for these
      predictions. However, for most realistic estimates of theta in natural
      populations, gene trees provide relatively good estimates of gamma, despite the
      disproportionate overestimation of younger node ages. This is corroborated with
      an empirical dataset of North American fence lizards (Sceloporus).

PMID- 21729044
TI  - Dealing with incomplete taxon sampling and diversification of a large clade of
      mushroom-forming fungi.
AB  - The absence of an adequate fossil record can hinder understanding the process of
      diversification that underlies the evolutionary history of a given group. In such
      cases, investigators have used ultrametric trees derived from molecular data from
      extant taxa to gain insights into processes of speciation and extinction over
      time. Inadequate taxon sampling, however, impairs such inferences. In this study,
      we use simulations to investigate the effect of incomplete taxon sampling on the
      accumulation of lineages through time for a clade of mushroom-forming fungi, the
      Hebelomateae. To achieve complete taxon sampling, we use a new Bayesian approach
      that incorporates substitute lineages to estimate diversification rates. Unlike
      many studies of animals and plants, we find no evidence of a slowdown in
      speciation. This indicates the Hebelomateae has not undergone an adaptive
      radiation. Rather, these fungi have evolved under a relatively constant rate of
      diversification since their most recent common ancestor, which we date back to
      the Eocene. The estimated net diversification rate (0.08-0.19 spp./lineage/Ma) is
      comparable with that of many plants and animals. We suggest that continuous
      diversification in the Hebelomateae has been facilitated by climatic and
      vegetation changes throughout the Cenozoic. We also caution against modeling
      multiple genes as a single partition when performing phylogenetic dating
      analyses.

PMID- 21729046
TI  - The genetic architecture of adaptation under migration-selection balance.
AB  - Many ecologically important traits have a complex genetic basis, with the
      potential for mutations at many different genes to shape the phenotype. Even so,
      studies of local adaptation in heterogeneous environments sometimes find that
      just a few quantitative trait loci (QTL) of large effect can explain a large
      percentage of observed differences between phenotypically divergent populations.
      As high levels of gene flow can swamp divergence at weakly selected alleles,
      migration-selection-drift balance may play an important role in shaping the
      genetic architecture of local adaptation. Here, we use analytical approximations
      and individual-based simulations to explore how genetic architecture evolves when
      two populations connected by migration experience stabilizing selection toward
      different optima. In contrast to the exponential distribution of allele effect
      sizes expected under adaptation without migration (Orr 1998), we find that
      adaptation with migration tends to result in concentrated genetic architectures
      with fewer, larger, and more tightly linked divergent alleles. Even if many small
      alleles contribute to adaptation at the outset, they tend to be replaced by a few
      large alleles under prolonged bouts of stabilizing selection with migration. All
      else being equal, we also find that stronger selection can maintain linked
      clusters of locally adapted alleles over much greater map distances than weaker
      selection. The common empirical finding of QTL of large effect is shown to be
      expected with migration in a heterogeneous landscape, and these QTL may often be
      composed of several tightly linked alleles of smaller effect.

PMID- 21729045
TI  - Diversity and demography in Beringia: multilocus tests of paleodistribution
      models reveal the complex history of arctic ground squirrels.
AB  - To assess effects of historical climate change on northern species, we quantified
      the population history of the arctic ground squirrel (Spermophilus parryii), an
      arctic-adapted rodent that evolved in Beringia and was strongly influenced by
      climatic oscillations of the Quaternary. Competing hypotheses for the species'
      population history were derived from patterns of mitochondrial (mtDNA) structure
      and a bioclimatic envelope model (BEM). Hypotheses invoked (1) sequential
      isolation of regional populations beginning with the Arctic, (2) deep isolation
      only across central Alaska, and (3) widespread panmixia, and were tested using
      coalescent methods applied to eight nuclear (nDNA) loci. The data rejected strict
      interpretations of all three hypotheses, but perspectives underlying each
      encompassed aspects of the species' history. Concordance between mtDNA and nDNA
      geographic structure revealed three semi-independently evolving phylogroups,
      whereas signatures of gene flow at nDNA loci were consistent with a historical
      contact between certain populations as inferred by the BEM. Demographic growth
      was inferred for all regions despite expectations of postglacial habitat
      contraction for parts of Beringia. Our results highlight the complementary
      perspectives on species' histories that multiple lines of evidence provide, and
      underscore the utility of multilocus data for resolving complex population
      histories relevant to understanding effects of climate change.

PMID- 21729047
TI  - The influence of an innovative locomotor strategy on the phenotypic
      diversification of triggerfish (family: Balistidae).
AB  - Innovations in locomotor morphology have been invoked as important drivers of
      vertebrate diversification, although the influence of novel locomotion strategies
      on marine fish diversification remains largely unexplored. Using triggerfish as a
      case study, we determine whether the evolution of the distinctive synchronization
      of enlarged dorsal and anal fins that triggerfish use to swim may have catalyzed
      the ecological diversification of the group. By adopting a comparative
      phylogenetic approach to quantify median fin and body shape integration and to
      assess the tempo of functional and morphological evolution in locomotor traits,
      we find that: (1) functional and morphological components of the locomotive
      system exhibit a strong signal of correlated evolution; (2) triggerfish
      partitioned locomotor morphological and functional spaces early in their history;
      and (3) there is no strong evidence that a pulse of lineage diversification
      accompanied the major episode of phenotypic diversification. Together these
      findings suggest that the acquisition of a distinctive mode of locomotion drove
      an early radiation of shape and function in triggerfish, but not an early
      radiation of species.

PMID- 21729048
TI  - The tempo and mode of evolution: body sizes of island mammals.
AB  - The tempo and mode of body size evolution on islands are believed to be well
      known. It is thought that body size evolves relatively quickly on islands toward
      the mammalian modal value, thus generating extreme cases of size evolution and
      the island rule. Here, we tested both theories in a phylogenetically explicit
      context, by using two different species-level mammalian phylogenetic hypotheses
      limited to sister clades dichotomizing into an exclusively insular and an
      exclusively mainland daughter nodes. Taken as a whole, mammals were found to show
      a largely punctuational mode of size evolution. We found that, accounting for
      this, and regardless of the phylogeny used, size evolution on islands is no
      faster than on the continents. We compared different selection regimes using a
      set of Ornstein-Uhlenbeck models to examine the effects of insularity of the mode
      of evolution. The models strongly supported clade-specific selection regimes.
      Under this regime, however, an evolutionary model allowing insular species to
      evolve differently from their mainland relatives performs worse than a model that
      ignores insularity as a factor. Thus, insular taxa do not experience
      statistically different selection from their mainland relatives.

PMID- 21729049
TI  - Mammals evolve faster on smaller islands.
AB  - Island mammals often display remarkable evolutionary changes in size and
      morphology. Both theory and empirical data support the hypothesis that island
      mammals evolve at faster rates than their mainland congeners. It is also often
      assumed that the island effect is stronger and that evolution is faster on the
      smallest islands. I used a dataset assembled from the literature to test these
      assumptions for the first time. I show that mammals on smaller islands do indeed
      evolve more rapidly than mammals on larger islands, and also evolve by a greater
      amount. These results fit well the theory of an evolutionary burst due to the
      opening of new ecological opportunities on islands. This evolutionary burst is
      expected to be the strongest on the smallest islands where the contrast between
      the island and the mainland environments is the most dramatic.

PMID- 21729050
TI  - Evolutionary advantage of small populations on complex fitness landscapes.
AB  - Recent experimental and theoretical studies have shown that small asexual
      populations evolving on complex fitness landscapes may achieve a higher fitness
      than large ones due to the increased heterogeneity of adaptive trajectories.
      Here, we introduce a class of haploid three-locus fitness landscapes that allow
      the investigation of this scenario in a precise and quantitative way. Our main
      result derived analytically shows how the probability of choosing the path of the
      largest initial fitness increase grows with the population size. This makes large
      populations more likely to get trapped at local fitness peaks and implies an
      advantage of small populations at intermediate time scales. The range of
      population sizes where this effect is operative coincides with the onset of
      clonal interference. Additional studies using ensembles of random fitness
      landscapes show that the results achieved for a particular choice of three-locus
      landscape parameters are robust and also persist as the number of loci increases.
      Our study indicates that an advantage for small populations is likely whenever
      the fitness landscape contains local maxima. The advantage appears at
      intermediate time scales, which are long enough for trapping at local fitness
      maxima to have occurred but too short for peak escape by the creation of multiple
      mutants.

PMID- 21729051
TI  - Interspecific X-chromosome and mitochondrial DNA introgression in the Iberian
      hare: selection or allele surfing?
AB  - Introgression from a resident species into an invading one is predicted to occur
      through the demographic process of "allele surfing," and to particularly affect
      genomic regions transmitted by the lower migrating sex, such as mtDNA. This could
      explain that northern Iberian populations of Lepus granatensis harbor high
      frequencies of mtDNA from L. timidus, an arctic hare it replaced there after
      deglaciation. We report that variation of introgressed timidus-like mtDNA
      reflects several predicted effects of this process: increasing frequency and
      diversity in the direction of expansion, strong perpendicular phylogeographic
      structure and signs of postglacial demographic growth. However, demographic
      inferences for the granatensis and timidus-like mtDNA lineages suggest the latter
      may have outcompeted the former in northern Iberia. Autosomal introgression
      occurs at low frequencies and species-wide rather than only in the north. If this
      difference with mtDNA resulted from sex-biased migration, an intermediate pattern
      should prevail for the X-chromosome, but we report species-wide and high
      frequency introgression of an X-fragment. Either selection favored this
      ubiquitous X-introgression, or more complex postglacial expansion patterns
      prevailed, with different consequences depending on the genomic and geographic
      region. This illustrates the difficulty of distinguishing demographic and
      selective effects and the need for genome and species-wide based demographic
      models.

PMID- 21729052
TI  - Genetics of hybrid male sterility among strains and species in the Drosophila
      pseudoobscura species group.
AB  - Taxa in the early stages of speciation may bear intraspecific allelic variation
      at loci conferring barrier traits in hybrids such as hybrid sterility.
      Additionally, hybridization may spread alleles that confer barrier traits to
      other taxa. Historically, few studies examine within- and between-species
      variation at loci conferring reproductive isolation. Here, we test for allelic
      variation within Drosophila persimilis and within the Bogota subspecies of D.
      pseudoobscura at regions previously shown to contribute to hybrid male sterility.
      We also test whether D. persimilis and the USA subspecies of D. pseudoobscura
      share an allele conferring hybrid sterility in a D. pseudoobscura bogotana
      genetic background. All loci conferred similar hybrid sterility effects across
      all strains studied, although we detected some statistically significant
      quantitative effect variation among D. persimilis alleles of some hybrid
      incompatibility QTLs. We also detected allelism between D. persimilis and D.
      pseudoobscura USA at a second chromosome hybrid sterility QTL. We hypothesize
      that either the QTL is ancestral in D. persimilis and D. pseudoobscura USA and
      lost in D. pseudoobscura bogotana, or gene flow transferred the QTL from D.
      persimilis to D. pseudoobscura USA. We discuss our findings in the context of
      population features that may contribute to variation in hybrid incompatibilities.

PMID- 21729053
TI  - Isolation barriers between petunia axillaris and Petunia integrifolia
      (Solanaceae).
AB  - The isolation barriers restricting gene flow between populations or species are
      of crucial interest for understanding how biological species arise and how they
      are maintained. Few studies have examined the entire range of possible isolation
      barriers from geographic isolation to next generation hybrid viability. Here, we
      present a detailed analysis of isolation barriers between two flowering plant
      species of the genus Petunia (Solanaceae). Petunia integrifolia and P. axillaris
      feature divergent pollination syndromes but can produce fertile hybrids when
      crossed in the laboratory. Both Petunia species are primarily isolated in space
      but appear not to hybridize in sympatry. Our experiments demonstrate that
      pollinator isolation is very high but not strong enough to explain the absence of
      hybrids in nature. However, pollinator isolation in conjunction with male gametic
      isolation (i.e., pollen-pistil interaction) can explain the lack of natural
      hybridization, while postzygotic isolation barriers are low or nonexistent. Our
      study supports the notion that reproductive isolation in flowering plants is
      mainly caused by pre- rather than postzygotic isolation mechanisms.

PMID- 21729054
TI  - Can reinforcement occur with a learned trait?
AB  - We use birdsong as a case study to ask whether reinforcement can occur via the
      spread of a genetically determined female preference for a socially inherited
      (learned) male trait. We envision secondary contact between two neighboring
      populations with different song dialects. An individual's ability to learn song
      is confined by a genetic predisposition: if predispositions are strong, there
      will be no phenotypic overlap in song between populations, whereas weak
      predispositions allow phenotypic overlap, or "mixed" song. To determine if
      reinforcement has occurred, we consider if an allele for within-population female
      mating preference, based on song, can spread, and whether population specific
      songs can concurrently be maintained at equilibrium. We model several scenarios,
      including costs to mating preferences, mating preferences in hybrids, and hybrids
      having the ability to learn pure songs. We find that when weak predispositions
      are fixed within a population reinforcement based on song cannot occur. However,
      when some individuals have strong predispositions, restricting phenotypic overlap
      between populations in the trait, reinforcement is only slightly inhibited from a
      purely genetic model. Generalizing beyond the example of song, we conclude that
      socially learned signals will tend to prohibit reinforcement, but it may still
      occur if some individuals acquire trait phenotypes genetically.

PMID- 21729055
TI  - Avian vision and the evolution of egg color mimicry in the common cuckoo.
AB  - Coevolutionary arms races are a potent force in evolution, and brood parasite
      host dynamics provide classical examples. Different host-races of the common
      cuckoo, Cuculus canorus, lay eggs in the nests of other species, leaving all
      parental care to hosts. Cuckoo eggs often (but not always) appear to match
      remarkably the color and pattern of host eggs, thus reducing detection by hosts.
      However, most studies of egg mimicry focus on human assessments or reflectance
      spectra, which fail to account for avian vision. Here, we use discrimination and
      tetrachromatic color space modeling of bird vision to quantify egg background and
      spot color mimicry in the common cuckoo and 11 of its principal hosts, and we
      relate this to egg rejection by different hosts. Egg background color and
      luminance are strongly mimicked by most cuckoo host-races, and mimicry is better
      when hosts show strong rejection. We introduce a novel measure of color mimicry
      "color overlap"-and show that cuckoo and host background colors increasingly
      overlap in avian color space as hosts exhibit stronger rejection. Finally,
      cuckoos with better background color mimicry also have better pattern mimicry.
      Our findings reveal new information about egg mimicry that would be impossible to
      derive by the human eye.

PMID- 21729056
TI  - The optimal sampling strategy for unfamiliar prey.
AB  - Precisely how predators solve the problem of sampling unfamiliar prey types is
      central to our understanding of the evolution of a variety of antipredator
      defenses, ranging from Mullerian mimicry to polymorphism. When predators
      encounter a novel prey item then they must decide whether to take a risk and
      attack it, thereby gaining a potential meal and valuable information, or avoid
      such prey altogether. Moreover, if predators initially attack the unfamiliar
      prey, then at some point(s) they should decide to cease sampling if evidence
      mounts that the type is on average unprofitable to attack. Here, I cast this
      problem as a "two-armed bandit," the standard metaphor for exploration
      exploitation trade-offs. I assume that as predators encounter and attack
      unfamiliar prey they use Bayesian inference to update both their beliefs as to
      the likelihood that individuals of this type are chemically defended, and the
      probability of seeing the prey type in the future. I concurrently use dynamic
      programming to identify the critical informational states at which predator
      should cease sampling. The model explains why predators sample more unprofitable
      prey before complete rejection when the prey type is common and explains why
      predators exhibit neophobia when the unfamiliar prey type is perceived to be
      rare.

PMID- 21729057
TI  - Inbreeding and reproductive investment in the ant Formica exsecta.
AB  - In social animals, inbreeding depression may manifest by compromising care or
      resources individuals receive from inbred group members. We studied the effects
      of worker inbreeding on colony productivity and investment in the ant Formica
      exsecta. The production of biomass decreased with increasing inbreeding, as did
      biomass produced per worker. Inbred colonies produced fewer gynes (unmated
      reproductive females), whereas the numbers of males remained unchanged. As a
      result, sex ratios showed increased male bias, and the fraction of workers
      increased among the diploid brood. Males raised in inbred colonies were smaller,
      whereas the weight of gynes remained unchanged. The results probably reflect a
      trade-off between number and quality of offspring, which is expected if the
      reproductive success of gynes is more dependent on their weight or condition than
      it is for males. As males are haploid (with the exception of abnormal diploid
      males produced in very low frequencies in this population), and therefore cannot
      be inbred themselves, the effect on their size must be mediated through the
      workers of the colony. We suggest the effects are caused by the inbred workers
      being less proficient in feeding the growing larvae. This represents a new kind
      of social inbreeding depression that may affect sex ratios as well as caste fate
      in social insects.

PMID- 21729058
TI  - Effect of recurrent selfing on inbreeding depression and mating system evolution
      in an autopolyploid plant.
AB  - Genome duplication resulting in polyploidy can have significant consequences for
      the evolution of mating systems. Most theory predicts that self-fertilization
      will be selectively favored in polyploids; however, many autopolyploids are
      outcrossing or mixed-mating. Here, we examine the hypothesis that the evolution
      of selfing is restricted in autopolyploids because the genetic cost of selfing
      (i.e., inbreeding depression) increases monotonically with successive generations
      of inbreeding. Using the herbaceous, autotetraploid plant Chamerion
      angustifolium, we generated populations with different inbreeding coefficients
      (F= 0, 0.17 and 0.36) through three consecutive generations of selfing and
      compared their magnitudes of inbreeding depression in a common environment.
      Mating system estimates for four natural populations confirmed that tetraploid
      selfing rates (s(m) = 0.25, SE = 0.02) are similar to those of diploids (s(m) =
      0.12, SE = 0.12; F1,2 = 1.34, P= 0.37) indicating that both cytotypes are
      predominantly outcrossing. Compared to an outbred control line, mean inbreeding
      depression for seed production, survival, and height (vegetative and total) in
      the inbred line differed among generations (inbreeding coefficients). Across all
      stages, inbreeding depression (relative to control) was positively related to
      generation (inbreeding coefficient). Although the initial costs of inbreeding in
      extant and newly synthesized polyploids may be low compared to diploids, the
      monotonic increase in inbreeding depression with repeated inbreeding may limit
      the extent to which selfing variants are favored.

PMID- 21729059
TI  - Sex ratio evolution under probabilistic sex determination.
AB  - Sex allocation theory has been remarkably successful at explaining the prevalence
      of even sex ratios in natural populations and at identifying specific conditions
      that can result in biased sex ratios. Much of this theory focuses on parental sex
      determination (SD) strategies. Here, we consider instead the evolutionary causes
      and consequences of mixed offspring SD strategies, in which the genotype of an
      individual determines not its sex, but the probability of developing one of
      multiple sexes. We find that alleles specifying mixed offspring SD strategies can
      generally outcompete alleles that specify pure strategies, but generate
      constraints that may prevent a population from reaching an even sex ratio. We use
      our model to analyze sex ratios in natural populations of Tetrahymena
      thermophila, a ciliate with seven sexes determined by mixed SD alleles. We show
      that probabilistic SD is sufficient to account for the occurrence of skewed sex
      ratios in natural populations of T. thermophila, provided that their effective
      population sizes are small. Our results highlight the importance of genetic drift
      in sex ratio evolution and suggest that mixed offspring SD strategies should be
      more common than currently thought.

PMID- 21729060
TI  - Genetic and environmental control of temporal and size-dependent sex allocation
      in a wind-pollinated plant.
AB  - Sex allocation in hermaphrodites can be affected by spatial and temporal
      variation in resources, especially in plants where size-dependent gender
      modification is commonplace. The evolution of sex allocation will depend on the
      relative importance of genetic and environmental factors governing patterns of
      investment in female and male function. In wind-pollinated plants, theoretical
      models predict a positive relation between size and male investment because of
      the fitness advantages associated with more effective pollen dispersal. Theory
      also predicts that the timing and allocation to each sex function should depend
      on available resources. We grew maternal half-sibling families of annual, wind
      pollinated, Ambrosia artemisiifolia in sun and shade treatments to investigate
      these predictions. There was significant genetic variation for female and male
      flower production in both sun and shade treatments. Size-dependent sex allocation
      occurred in the direction predicted by theory, with male flower production
      increasing more rapidly in larger plants. The timing of sex function also varied,
      with significant genetic variation for dichogamy within environments and
      plasticity of this trait between environments. Protandry was expressed more
      commonly in the sun and protogyny in the shade. The occurrence of dynamic sex
      allocation with changing size and experimental treatment indicates the potential
      for adaptive responses under different ecological conditions.

PMID- 21729061
TI  - A theoretical model of the evolution of maternal effects under parent-offspring
      conflict.
AB  - The evolution of maternal effects on offspring phenotype should depend on the
      extent of parent-offspring conflict and costs and constraints associated with
      maternal and offspring strategies. Here, we develop a model of maternal effects
      on offspring dispersal phenotype under parent-offspring conflict to evaluate such
      dependence. In the absence of evolutionary constraints and costs, offspring
      evolve dispersal rates from different patch types that reflect their own, rather
      than the maternal, optima. This result also holds true when offspring are unable
      to assess their own environment because the maternal phenotype provides an
      additional source of information. Consequently, maternal effects on offspring
      diapause, dispersal, and other traits that do not necessarily represent costly
      resource investment are more likely to maximize offspring than maternal fitness.
      However, when trait expression was costly, the evolutionarily stable dispersal
      rates tended to deviate from those under both maternal and offspring control. We
      use our results to (re)interpret some recent work on maternal effects and their
      adaptive value and provide suggestions for future work.

PMID- 21729062
TI  - Evidence for strong intralocus sexual conflict in the Indian meal moth, Plodia
      interpunctella.
AB  - Males and females share a genome and express many shared phenotypic traits, which
      are often selected in opposite directions. This generates intralocus sexual
      conflict that may constrain trait evolution by preventing the sexes from reaching
      their optimal phenotype. Furthermore, if present across multiple loci, intralocus
      sexual conflict can result in a gender load that may diminish the benefits of
      sexual selection and help maintain genetic variation for fitness. Despite the
      importance of intralocus sexual conflict, surprisingly few empirical studies
      conclusively demonstrate its operation. We show that the pattern of multivariate
      selection acting on three sexually dimorphic life-history traits (development
      time, body size, and longevity) in the Indian meal moth, Plodia interpunctella,
      is opposing for the sexes. Moreover, we combined our estimates of selection with
      the additive genetic variance-covariance matrix (G) to predict the evolutionary
      response of the life-history traits in the sexes and showed that the angle
      between the vector of responses and the vector of sexually antagonistic selection
      was almost orthogonal at 84.70 degrees . Thus, G biases the predicted response of
      life-history traits in the sexes away from the direction of sexually antagonistic
      selection, confirming the presence of strong intralocus sexual conflict in this
      species. Despite this, sexual dimorphism has evolved in all of the life-history
      traits examined suggesting that mechanism(s) have evolved to resolve this
      conflict and allow the sexes to reach their life-history optima. We argue that
      intralocus sexual conflict is likely to play an important role in the evolution
      of divergent life-history strategies between the sexes in this species.

PMID- 21729063
TI  - Variation in compound eye structure: effects of diet and family.
AB  - Studies of compound eyes have revealed that variation in eye structure can
      substantially affect visual performance. Here, we investigate the degree to which
      a stressful rearing environment, which decreases body size, affects the eye
      phenotype. Full siblings of the Orange Sulphur butterfly, Colias eurytheme, were
      collected from known parents and split within families among two diet treatments
      that varied in quality. In both sexes, individuals reared on the high-quality
      diet had larger eye height and anterior facet diameter, and therefore, by
      inference, superior vision. However, relative to their reduced body size,
      individuals reared on low-quality diet had proportionally larger eyes and facets
      than individuals reared on high-quality diet. We interpret this finding as
      evidence that butterflies encountering nutritional stress increased proportional
      investment in eye development to reduce loss of visual performance. We also found
      significant broad-sense genetic variation underlying eye structure in both males
      and females, and report novel heritability estimates for eye height and facet
      diameter. Surprisingly, there was greater genetic variation in eye height among
      males than among females, despite apparently stronger directional selection on
      male vision. We discuss the implications of these data for our understanding of
      eye development and evolution.

PMID- 21729064
TI  - Assortative mating by fitness and sexually antagonistic genetic variation.
AB  - Recent documentations of sexually antagonistic genetic variation in fitness have
      spurred an interest in the mechanisms that may act to maintain such variation in
      natural populations. Using individual-based simulations, I show that positive
      assortative mating by fitness increases the amount of sexually antagonistic
      genetic variance in fitness, primarily by elevating the equilibrium frequency of
      heterozygotes, over most of the range of sex-specific selection and dominance.
      Further, although the effects of assortative mating by fitness on the protection
      conditions of polymorphism in sexually antagonistic loci were relatively minor,
      it widens the protection conditions under most reasonable scenarios (e.g., under
      heterozygote superiority when fitness is averaged across the sexes) but can also
      somewhat narrow the protection conditions under other circumstances. The near
      ubiquity of assortative mating in nature suggests that it may contribute to
      upholding standing sexually antagonistic genetic variation in fitness.

PMID- 21729065
TI  - Evolution of increased self-sperm production in postdauer hermaphroditic
      nematodes.
AB  - A recent study suggests that postdauer Caenorhabditis elegans hermaphrodites
      produce more self-sperm and have larger brood sizes than worms that bypass
      diapause. Why might natural selection favor increased self-sperm production in
      postdauer hermaphrodites? This question is addressed by developing an age
      structured model for an exponentially growing worm population descending from a
      founder postdauer hermaphrodite. It is assumed that natural selection favors
      those founders that have the largest number of living descendants at some fixed
      future time. Increased self-sperm production in postdauer hermaphrodites can then
      evolve when the diapause-bypassing descendants suffer a higher mortality rate
      than their parental postdauer founders.

PMID- 21729066
TI  - Establishment and maintenance of adaptive genetic divergence under migration,
      selection, and drift.
AB  - There is a long tradition in population genetics of exploring the maintenance of
      variation under migration-selection balance using deterministic models that
      assume infinite population size. With finite population size, stochastic dynamics
      can greatly reduce the potential for the maintenance of polymorphism, but this
      has yet to be explored in detail. Here, classical two-patch models are extended
      to predict: (1) the probability of a locally beneficial mutation rising in
      frequency in the patch where it is favored and (2) the critical threshold
      migration rate above which the maintenance of polymorphism is much less likely.
      Individual-based simulations show that these approximations provide accurate
      predictions across a wide range of parameter space.

PMID- 21729068
TI  - Observations on the flight paths of the day-flying moth Virbia lamae during
      periods of mate location: do males have a strategy for contacting the pheromone
      plume?
AB  - 1. To maximize the probability of rapid contact with a female's pheromone plume,
      the trajectories of male foraging flights might be expected to be directed with
      respect to wind flow and also to be energetically efficient. 2. Flights directed
      either upwind, downwind, or crosswind have been proposed as optimal strategies
      for rapid and/or energetically efficient plume contact. Other possible strategies
      are random and Levy walks, which have trajectories and turn frequencies that are
      not dictated by the direction of wind flow. 3. The planar flight paths of males
      of the day-active moth Virbia lamae were recorded during the customary time of
      its sexual activity. 4. We found no directional preference in these foraging
      flights with respect to the direction of contemporaneous wind flow, but, because
      crosswind encompasses twice the possible orientations of either upwind or
      downwind, a random orientation is in effect a de facto crosswind strategy. 5. A
      crosswind preference should be favoured when the plume extends farther downwind
      than crosswind, and this strategy is realized by V. lamae males by a random
      orientation of their trajectories with respect to current wind direction.

PMID- 21729069
TI  - Quantity of the tetracycline resistance gene tet(M) differs substantially between
      meat at slaughterhouses and at retail.
AB  - Concentrations of the tetracycline resistance gene tet(M) per square centimeter
      were assessed in meat from the slaughterhouse (n = 100) and from retail (n = 100)
      by real-time quantitative PCR. The study revealed a substantial contamination of
      retail meat with the tetracycline resistance gene tet(M), with a mean of 4.34 log
      copies per cm2 fasces in chicken and 5.58 log copies per cm2 fasces in pork.
      Quantitative resistance gene analysis provides an interesting tool for risk
      assessment and is becoming increasingly important. For both chicken and pork,
      tet(M) concentrations were significantly higher in meat at retail, compared to
      meat at slaughter. Cultural investigations revealed substantial differences in
      the prevalence of listeria and enterococci, and of E. coli and coliforms, between
      meat at slaughter (n = 500) and at retail (n = 500). However, the differences in
      the prevalence of 2 investigated groups of potential tet(M)-carriers
      (enterococci, listeria) could not sufficiently explain the differences in tet(M)
      concentrations, since increasing concentrations of tet(M) were accompanied by
      decreasing prevalences of these potential tet(M)-carriers. The percentage of
      tetracycline susceptible indicator bacteria (E. faecalis, E. coli) did not differ
      between meat at slaughter and meat at retail. Higher concentrations of tet(M) at
      retail might correlate with the proliferation of other genera than enterococci
      and listeria, but there is also a reason to discuss whether secondary
      contaminants might carry tet(M) more often than the primary flora of meat.
      PRACTICAL APPLICATION: We successfully applied the direct quantitative monitoring
      of resistance genes in meat, which generally might aid as a useful and rapid
      additional tool for risk assessment. We know that bacteria provide a large pool
      of resistance genes, which are widely shared between each other-the larger the
      pool is, the more genes might be exchanged. Thus, in terms of resistance gene
      monitoring, we should sometimes overcome the restricted view on single bacteria
      and look at the gene pool, instead.

PMID- 21729070
TI  - Concentration of soy protein isolate affects starch-based confections' texture,
      sensory, and storage properties.
AB  - The effects of increasing soy protein isolate concentration on the physico
      chemical properties of starch-based grape confectionery gels were investigated
      using thermal, textural, and sensory analyses. Soy protein isolate decreased
      hardness, cohesiveness, and gumminess, demonstrating potential as a texture
      modifier. Increasing soy protein concentration progressively decreased the
      elastic properties of the starch network demonstrated by a lower G'-G" crossover
      frequency. High levels of soy protein also created a more homogeneous water
      population, one which was lost at lower temperatures compared to standard
      confections. An improvement in taste and texture acceptability of the confections
      upon addition of soy protein isolate was found by sensory analysis. Finally,
      physico-chemical properties were compared up to 20 d of storage at ambient
      temperature. Soy-containing confections demonstrated lower gumminess and
      cohesiveness during the entire storage period but a significant increase in
      hardness after 20 d of storage. PRACTICAL APPLICATION: Soy protein isolate
      imparted soft texture to starch-based confections on a concentration-dependent
      basis. Increasing soy protein isolate concentration decreased elastic properties
      of the starch network in starch confections and significantly improved flavor and
      texture. Gumminess and cohesiveness of soy protein isolate confection was lower
      during 20 d of storage.

PMID- 21729071
TI  - Effects of turmeric, shallot extracts, and their combination on quality
      characteristics of vacuum-packaged rainbow trout stored at 4 +/- 1  degrees C.
AB  - The effects of turmeric extract (T), shallot extract (Sh), and their combination
      (T + Sh) on the quality of vacuum-packaged rainbow trout (Oncorhynchus mykiss)
      were examined during refrigerated storage (4 +/- 1  degrees C) over a period of
      20 d. Fish samples were divided into 4 batches; 3 batches were treated by dipping
      for 30 min in aqueous solution of turmeric extract (1.5%; v/v), shallot extract
      (1.5%; v/v), or turmeric and shallot extract combination (1.5%+ 1.5% v/v), while
      the fourth batch was dipped in distilled water as a control sample. The control
      and the treated fish samples were analyzed periodically for microbiological
      (total viable count, psychrotrophic count), chemical (total volatile base
      nitrogen [TVB-N], peroxide value [PV], and thiobarbituric acid [TBA] value), and
      sensory characteristics. The results indicated that the effect of the T, Sh, and
      T + Sh on the fish samples were to enable the good quality characteristics to be
      retained longer and to extend the shelf life during the refrigerated storage.

PMID- 21729072
TI  - Effects of high-pressure process on kinetics of leaching oil from soybean powder
      using hexane in batch systems.
AB  - Mass transfer models of leaching oil from soybean (Glycine max) flour with hexane
      after high-pressure process (HPP) treatment were developed. High pressure (450
      MPa) was applied to the soybean flour (mean diameter of flour particle: 365 MUm)
      for 30 min before leaching the oil components in the solvent. The ratio of
      solvent (volume, mL) to soybean flour (mass, g), such as 1:10 and 1:20, was
      employed to characterize the effect of solvent ratio on the leaching rate in the
      batch type of extraction process. Ultraviolet absorbance at 300 nm was used to
      monitor the extraction rate. Saturation solubility (C(AS)) was determined to be
      21.73 kg/m3. The mass transfer coefficients (k) were determined based on the 1st-
      and 2nd-order kinetic models. The 2nd kinetic model showed better fit. The HPP
      treatment showed a higher extraction rate and yield compared to the control,
      while the amount of solvent did not affect the extraction rate and yield. The
      scanning electron microscope showed that HPP-treated soybean particles included
      more pores than the untreated. The pores observed in the HPP-treated soybean
      flours might help increase the mass transfer rate of solvent and solute in the
      solid matrix. PRACTICAL APPLICATION: High-pressure processing can help increase
      the extraction rate of oil from the soybean flour operated in batch systems. The
      conventional solid to solvent ratio (1:20) used to extract oil composition from
      the plant seed did not help increase the amount of oil extracted from the soybean
      flour.

PMID- 21729073
TI  - Antifungal activity of 2 lactic acid bacteria of the Weissella genus isolated
      from food.
AB  - In the present study, a total of 116 lactic acid bacteria (LAB) strains isolated
      from Mill flour and fermented cassava were screened for their antifungal
      activity. Three strains among 116 were selected for their strongest inhibitory
      activity against food molds. These 3 strains were Lactobacillus plantarum VE56,
      Weissella cibaria FMF4B16, and W. paramesenteroides LC11. The compounds
      responsible for the antifungal activity were investigated. The strains displayed
      an inhibitory activity against targeted molds at acidic pH. However, the
      influence of organic acids was rejected according to the calculated minimal
      inhibitory concentration (MIC). Antifungal compounds were investigated in the
      cell-free supernatants and phenyllactic acid (PLA) was detected in different
      amounts with a maximal concentration for Lb. plantarum VE56 (0.56 mM). Hydroxy
      fatty acid, such as 2-hydroxy-4-methylpentanoic acid, was also produced and
      involved in the inhibitory activity of Lb. plantarum VE56 and W.
      paramesenteroides LC11. Antifungal LAB are known to produce PLA and 3-hydroxy
      fatty acids and other organic acids with antifungal activity. This short
      communication focuses on antifungal activity from Weissella genus. The antifungal
      activity was attributed to antifungal compounds identified such as PLA, 2-hydroxy
      4-methylpentanoic acid, and other organic acids. Nevertheless, the concentration
      produced in the cell-free supernatant was too low to compare to their MIC,
      suggesting that the inhibitory activity was caused by a synergy of these
      different compounds. PRACTICAL APPLICATION: Antifungal LAB are interesting to
      prevent food spoilage in fermented food and prolong their shelf life. In this
      way, chemical preservatives could be avoided and replaced by natural
      preservatives.

PMID- 21729074
TI  - Microbial safety and consumer acceptability of high-pressure processed hard clams
      (Mercenaria mercenaria).
AB  - Littleneck hard clams (Mercenaria mercenaria) harvested from New Jersey coastal
      waters in the United States were high-pressure processed (HPP) in their shells
      using a 10 L high-pressure processing unit. A response surface (RS) methodology
      approach was used to optimize the pressure and time parameters for microbial
      inactivation caused by the high-pressure application. The total surviving
      microbial load in the hard clams was enumerated after processing at each
      experimental condition. The results indicated that log reduction in total plate
      count (TPC) due to high-pressure processing of hard clams was primarily a
      function of pressure. Pressure of at least 480 MPa was needed to achieve 1-log
      reduction in TPC in hard clams harvested from special restricted waters. In a
      parallel study, a panel of 60 regular raw clams consumers tasted both raw and
      processed hard clams that were harvested from approved waters and HPP at 310 MPa
      for 3 min. The consumers showed equal preference for processed and raw hard
      clams. Two subgroups of hard clam consumers were revealed; 1 group preferred the
      plumpness of the HPP clam and the other group preferred aroma of the unprocessed
      clam. Thus, plumpness and aroma may influence consumer acceptance of HPP hard
      clams. PRACTICAL APPLICATION: High-pressure processing has gained momentum as a
      processing technique that aids in retention of fresh appearance in foods. It
      holds promise as a method to process premium value food products while retaining
      quality attributes. Quantification of its impact on safety and consumer
      acceptance is critical for its acceptance and use in the food industry.

PMID- 21729075
TI  - Sensory shelf-life limiting factor of high hydrostatic pressure processed avocado
      paste.
AB  - High hydrostatic pressure (HHP) processing pasteurizes avocado paste without a
      significant impact on flavor. Although HHP-treated avocado paste stored under
      refrigeration is safe for human consumption for months, sensory changes taking
      place during storage cause the rejection of the product by consumers within days.
      Although it is known that the shelf life of the product ends before its microbial
      counts are high, its sensory shelf life limiting factor remains unknown. The
      present study focused on the use of a trained panel and a consumer panel to
      determine the sensory shelf life limiting factor of HHP-treated avocado paste.
      The trained panel identified sour and rancid flavors as the main sensory
      descriptors (critical descriptors) that differentiated stored from freshly
      processed samples. Further data obtained from consumers identified sour flavor as
      the main cause for a significant decrease in the acceptability (shelf life
      limiting factor) of refrigerated HHP-treated avocado paste. The study allowed the
      elucidation of a proposed deterioration mechanism for HHP-treated avocado paste
      during its refrigerated shelf life. The information through this work enhances
      scientific knowledge of the product and proposes the sour flavor development
      during storage as a relevant sensory attribute that needs to be improved in order
      to enhance the product shelf life. PRACTICAL APPLICATION: At present, HHP is the
      most effective commercial nonthermal technology to process avocado paste when
      compared to thermal and chemical alternatives. HHP-treated avocado paste is a
      microbiologically stable food for a period of at least 45 d stored under
      refrigeration. However, previous published work indicated that consumers rejected
      the product after approximately 19 d of storage due to sensory changes. This
      manuscript presents a sensory study that permitted the identification of the
      critical sensory descriptor that is acting as the sensory shelf life limiting
      factor of the product. The data presented herein along with previous reported
      data allows a better understanding of the deterioration mechanism that occurs
      during the storage of HHP-treated avocado paste. This information is relevant and
      useful for the elucidation of possible alternatives to enhance the shelf life of
      HHP-treated avocado paste.

PMID- 21729076
TI  - Inhibition of Escherichia coli O157:H7 and Clostridium sporogenes in spinach
      packaged in modified atmospheres after treatment combined with chlorine and
      lactic acid bacteria.
AB  - Implementation of modified atmospheric packaging (MAP) into retail produce is a
      less commonly practiced method due to differences among commodities and the
      potential growth of anaerobes. Pathogens including Escherichia coli O157:H7 have
      been responsible for spinach outbreaks across the United States. In this study,
      hurdles, including those currently used with produce safety, such as MAP and
      chlorine, were combined with lactic acid bacteria (LAB) to inhibit pathogens.
      Spinach was coinoculated with E. coli O157:H7 and Clostridium sporogenes, a
      surrogate for C. botulinum, and treated with water or a hurdle that included
      water, chlorine, and LAB. Spinach from treatments were packaged in air
      (traditional), oxygen (80% O2, 20% CO2), or nitrogen (80% N2, 20% CO2) and stored
      in a retail display case for 9 d at 4 to 7  degrees C. The hurdle inhibited E.
      coli O157:H7 and C. sporogenes compared to controls with reductions of 1.43 and
      1.10 log (P < 0.05), respectively. The nitrogen atmosphere was outperformed by
      air and oxygen in the reduction of E. coli O157:H7 (P < 0.05) with a decrease of
      0.26 and 0.15 logs. There were no significant differences among the 3 atmospheres
      on C. sporogenes survival. Relative to these hurdles, we also chose to evaluate
      the potential benefits of LAB in pathogen control. The survival of LAB in
      interventions demonstrates implementation of LAB into produce could control
      pathogens, without damaging produce or altering organoleptic properties.
      PRACTICAL APPLICATION: The goal of our work was to identify methods that could
      reduce food-borne pathogens in packaged spinach products. Using current industry
      techniques in combination with unique methods, such as the use of beneficial
      bacteria, our research identified whether harmful microorganisms could be
      eliminated. Our data demonstrate that specific packaging conditions with
      beneficial bacteria can help eliminate or reduce the survival of E. coli O157:H7
      and C. sporogenes (a model for C. botulinum) in produce.

PMID- 21729077
TI  - Anthocyanins remain stable during commercial blackcurrant juice processing.
AB  - It remains important to establish the stability of anthocyanins throughout
      commercial processing in order to maintain the bioactivity of the processed
      food/s. The present study aimed to assess the recovery and formation of
      anthocyanins and their free phenolic acid degradation products during the
      commercial processing of blackcurrant juice concentrate. A bench-scale processing
      model was also established to allow for alteration of predefined parameters to
      identify where commercial processes could be modified to influence anthocyanin
      yield. No significant loss in anthocyanins was observed throughout the commercial
      processing of blackcurrants, from whole berry through milling, to pectin
      hydrolysis and sodium bisulphite addition (P >= 0.7). No significant loss in
      anthocyanins was observed following the subsequent processing of pressed juice,
      through pasteurization, decantation, filtration, and concentration (P >= 0.9).
      Similarly, the bench-scale model showed no significant losses in anthocyanin
      content except during pasteurization (22%+/- 0.7%, P < 0.001). In the full
      factorial Design of Experiment model analysis, only sodium bisulphite
      concentration had an impact on anthocyanin recovery, which resulted in an
      increase (23% to 27%; P < 0.001) in final anthocyanin concentration. No phenolic
      degradation products (free protocatechuic acid or gallic acid derived from
      cyanidin and delphinin species, respectively) were identified in any processed
      sample when compared to authentic analytical standards, analyzed by ultra
      performance liquid chromatography DAD. PRACTICAL APPLICATION: This article
      provides crucial data directly applicable to commercial juice processing, such as
      improving anthocyanin yield and practical considerations for anthocyanin
      stability and degradation. This aspect is particularly pertinent considering the
      current commercial interest in anthocyanin-derived phenolic acids and their
      health-related benefits. Further research and development targets in the area of
      commercial juice product development are identified.

PMID- 21729078
TI  - Microencapsulated antimicrobial compounds as a means to enhance electron beam
      irradiation treatment for inactivation of pathogens on fresh spinach leaves.
AB  - Recent outbreaks associated to the consumption of raw or minimally processed
      vegetable products that have resulted in several illnesses and a few deaths call
      for urgent actions aimed at improving the safety of those products. Electron beam
      irradiation can extend shelf-life and assure safety of fresh produce. However,
      undesirable effects on the organoleptic quality at doses required to achieve
      pathogen inactivation limit irradiation. Ways to increase pathogen radiation
      sensitivity could reduce the dose required for a certain level of microbial kill.
      The objective of this study was to evaluate the effectiveness of using natural
      antimicrobials when irradiating fresh produce. The minimum inhibitory
      concentration of 5 natural compounds and extracts (trans-cinnamaldehyde, eugenol,
      garlic extract, propolis extract, and lysozyme with ethylenediaminetetraacetate
      acid (disodium salt dihydrate) was determined against Salmonella spp. and
      Listeria spp. In order to mask odor and off-flavor inherent of several compounds,
      and to increase their solubility, complexes of these compounds and extracts with
      beta-cyclodextrin were prepared by the freeze-drying method. All compounds showed
      bacteriostatic effect at different levels for both bacteria. The effectiveness of
      the microencapsulated compounds was tested by spraying them on the surface of
      baby spinach inoculated with Salmonella spp. The dose (D10 value) required to
      reduce the bacterial population by 1 log was 0.190 kGy without antimicrobial
      addition. The increase in radiation sensitivity (up to 40%) varied with the
      antimicrobial compound. These results confirm that the combination of spraying
      microencapsulated antimicrobials with electron beam irradiation was effective in
      increasing the killing effect of irradiation. PRACTICAL APPLICATION: Foodborne
      illness outbreaks attributed to fresh produce consumption have increased and
      present new challenges to food safety. Current technologies (water washing or
      treating with 200 ppm chlorine) cannot eliminate internalized pathogens. Ionizing
      radiation is a viable alternative for eliminating pathogens; however, the dose
      required to inactivate these pathogens is often too high to be tolerated by the
      fresh produce without undesirable quality changes. This study uses natural
      antimicrobial ingredients as radiosensitizers. These ingredients were
      encapsulated and applied to fresh produce that was subsequently irradiated. The
      process results in high level of microorganism inactivation using lower doses
      than the conventional irradiation treatments.

PMID- 21729079
TI  - Effect of input data variability on estimations of the equivalent constant
      temperature time for microbial inactivation by HTST and retort thermal
      processing.
AB  - Consumer demand for food safety and quality improvements, combined with new
      regulations, requires determining the processor's confidence level that processes
      lowering safety risks while retaining quality will meet consumer expectations and
      regulatory requirements. Monte Carlo calculation procedures incorporate input
      data variability to obtain the statistical distribution of the output of
      prediction models. This advantage was used to analyze the survival risk of
      Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) and
      Clostridium botulinum spores in high-temperature short-time (HTST) milk and
      canned mushrooms, respectively. The results showed an estimated 68.4% probability
      that the 15 sec HTST process would not achieve at least 5 decimal reductions in
      M. paratuberculosis counts. Although estimates of the raw milk load of this
      pathogen are not available to estimate the probability of finding it in
      pasteurized milk, the wide range of the estimated decimal reductions, reflecting
      the variability of the experimental data available, should be a concern to dairy
      processors. Knowledge of the C. botulinum initial load and decimal thermal time
      variability was used to estimate an 8.5 min thermal process time at 110  degrees
      C for canned mushrooms reducing the risk to 10-9 spores/container with a 95%
      confidence. This value was substantially higher than the one estimated using
      average values (6.0 min) with an unacceptable 68.6% probability of missing the
      desired processing objective. Finally, the benefit of reducing the variability in
      initial load and decimal thermal time was confirmed, achieving a 26.3% reduction
      in processing time when standard deviation values were lowered by 90%. PRACTICAL
      APPLICATION: In spite of novel technologies, commercialized or under development,
      thermal processing continues to be the most reliable and cost-effective
      alternative to deliver safe foods. However, the severity of the process should be
      assessed to avoid under- and over-processing and determine opportunities for
      improvement. This should include a systematic approach to consider variability in
      the parameters for the models used by food process engineers when designing a
      thermal process. The Monte Carlo procedure here presented is a tool to facilitate
      this task for the determination of process time at a constant lethal temperature.

PMID- 21729080
TI  - Improvement of gel strength and melting point of fish gelatin by addition of
      coenhancers using response surface methodology.
AB  - Fish gelatin is a potential alternative to mammalian gelatin. However, poor gel
      strength and low melting point limit its applications. The study was aimed at
      improving these properties by adding coenhancers in the range obtained from
      response surface methodology (RSM) by using Box-Behnken design. Three different
      coenhancers, MgSO4, sucrose, and transglutaminase were used as the independent
      variables for improving the gel strength and melting point of gelatin extracted
      from Tiger-toothed croaker (Otolithes ruber). Addition of coenhancers at
      different combinations resulted gel strength and melting point in the range of
      150.5 to 240.5 g and 19.5 to 22.5  degrees C, respectively. The optimal
      concentrations of coenhancers for predicted maximum gel strength (242.8 g)
      obtained by RSM were 0.23 M MgSO4, 12.60% sucrose (w/v), and 5.92 mg/g
      transglutaminase and for predicted maximum melting point (22.57  degrees C), the
      values were 0.24 M MgSO4, 10.44% sucrose (w/v), and 5.72 mg/g transglutaminase.
      By addition of coenhancers at these optimal concentrations in verification
      experiments, the gel strength and melting point were improved from 170 to 240.89
      g and 20.3 to 22.7  degrees C, respectively. These experimental values agreed
      well with the predicted values demonstrating the fitness of the models. Results
      from the present study clearly revealed that the addition of coenhancers at a
      particular combination can improve the gel strength and melting point of fish
      gelatin to enhance its range of applications. PRACTICAL APPLICATION: There is a
      growing interest in the use of fish gelatin as an alternative to mammalian
      gelatin. However, poor gel strength and low melting point of fish gelatin have
      limited its commercial applications. The gel strength and melting point of fish
      gelatin can be increased by incorporation of coenhancers such as magnesium
      sulphate, sucrose, and transglutaminase. Results of this work help to produce the
      fish gelatin suitable for wide range of applications in the food industry.

PMID- 21729081
TI  - Forensic identification science evidence since Daubert: Part II--judicial
      reasoning in decisions to exclude forensic identification evidence on grounds of
      reliability.
AB  - Many studies regarding the legal status of forensic science have relied on the
      U.S. Supreme Court's mandate in Daubert v. Merrell Dow Pharmaceuticals Inc., and
      its progeny in order to make subsequent recommendations or rebuttals. This paper
      focuses on a more pragmatic approach to analyzing forensic science's immediate
      deficiencies by considering a qualitative analysis of actual judicial reasoning
      where forensic identification evidence has been excluded on reliability grounds
      since the Daubert precedent. Reliance on general acceptance is becoming
      insufficient as proof of the admissibility of forensic evidence. The citation of
      unfounded statistics, error rates and certainties, a failure to document the
      analytical process or follow standardized procedures, and the existence of
      observe bias represent some of the concerns that have lead to the exclusion or
      limitation of forensic identification evidence. Analysis of these reasons may
      serve to refocus forensic practitioners' testimony, resources, and research
      toward rectifying shortfalls in these areas.

PMID- 21729082
TI  - Ear identification: a pilot study.
AB  - Although several papers have recently been devoted to establishing the validity
      of identification using the ear, this part of the human body still remains
      underexploited in forensic science. The perfect overlap of two images of the same
      ear is not really possible, but photographs of the ears as a reliable means of
      inferring the identity of an individual are poorly treated in the literature. In
      this study, we illustrate a simple, reproducible method, which divides the
      photograph of an ear into four parts-helix, antihelix, concha, and lobe-by means
      of a suitable grid of four straight lines. Although the division does not follow
      exact anatomical features, their edges do join anatomical points which are more
      easily identifiable. Measurement of certain areas of these parts can be combined
      to produce a code allowing personal identification. This method produces false
      positive identifications of <0.2%. Last, the repeatability and reproducibility
      aspects of the method are tested.

PMID- 21729083
TI  - Commentary on: Schmitt MW, Williams TL, Woodard KR, Harruff RC. Trends in suicide
      by carbon monoxide inhalation in King County, Washington: 1996-2009. J Forensic
      Sci 2011; Feb 3. doi: 10.1111/j.1556-4029.2010.01688.x [Epub ahead of print].

PMID- 21729085
TI  - Commentary on: Jauchem J. Increased hematocrit after applications of conducted
      energy weapons (including TASER devices) to Sus scrofa. J Forensic Sci 2011;56
      (S1): S229-33.

PMID- 21729086
TI  - Establishing a time-scale for plant evolution.
AB  - * Plants have utterly transformed the planet, but testing hypotheses of causality
      requires a reliable time-scale for plant evolution. While clock methods have been
      extensively developed, less attention has been paid to the correct interpretation
      and appropriate implementation of fossil data. * We constructed 17 calibrations,
      consisting of minimum constraints and soft maximum constraints, for divergences
      between model representatives of the major land plant lineages. Using a data set
      of seven plastid genes, we performed a cross-validation analysis to determine the
      consistency of the calibrations. Six molecular clock analyses were then
      conducted, one with the original calibrations, and others exploring the impact on
      divergence estimates of changing maxima at basal nodes, and prior probability
      densities within calibrations. * Cross-validation highlighted Tracheophyta and
      Euphyllophyta calibrations as inconsistent, either because their soft maxima were
      overly conservative or because of undetected rate variation. Molecular clock
      analyses yielded estimates ranging from 568-815 million yr before present (Ma)
      for crown embryophytes and from 175-240 Ma for crown angiosperms. * We reject
      both a post-Jurassic origin of angiosperms and a post-Cambrian origin of land
      plants. Our analyses also suggest that the establishment of the major embryophyte
      lineages occurred at a much slower tempo than suggested in most previous studies.
      These conclusions are entirely compatible with current palaeobotanical data,
      although not necessarily with their interpretation by palaeobotanists.

PMID- 21729087
TI  - Adaptive genetic differentiation in a predominantly self-pollinating species
      analyzed by transplanting into natural environment, crossbreeding and Q(ST)-F(ST)
      test.
AB  - * Both genetic drift and natural selection result in genetic/phenotypic
      differentiation over space. I analyzed the role of local adaptation in the
      genetic differentiation of populations of the annual grass Hordeum spontaneum
      sampled along an aridity gradient. * The study included the introduction of
      plants having desert vs nondesert origin into natural (desert) environment,
      analysis of population differentiation in allozymes and random amplified
      polymorphic DNA (RAPD) markers vs phenotypic traits (Q(ST) -F(ST) comparison),
      and planting interpopulation hybrids under simulated desert conditions in a
      glasshouse. * The results of the home advantage test, Q(ST) -F(ST) comparison and
      crossbreeding were consistent with local adaptation; that is, that
      differentiation of the desert plants from plants of nondesert origin in
      phenotypic traits was adaptive, giving them home advantage. Each method used
      provided additional, otherwise unavailable, information, meaning that they should
      be viewed as complementary rather than alternative approaches. * Gene flow from
      adjacent populations (i.e. populations experiencing the desert environment) via
      seeds (but not pollen) had a positive effect on fitness by enhancing natural
      selection and counteracting drift. At the same time, the effect of genes from the
      species distributional core (nondesert plants) by either seed or pollen had a
      negative fitness effect despite its enriching effect on neutral diversity. The
      pattern of outbreeding depression observed in interpopulation hybrids (F(1) ) and
      their segregating progeny (F(2) ) was inconsistent with underdominance, but
      indicated the presence of additive, dominance and epistatic effects.

PMID- 21729088
TI  - Are vascular epiphytes nitrogen or phosphorus limited? A study of plant (15) N
      fractionation and foliar N : P stoichiometry with the tank bromeliad Vriesea
      sanguinolenta.
AB  - Although there is unambiguous evidence for vascular epiphytic plants to be
      limited by insufficient water and nutrient supply under natural conditions, it is
      an open debate whether they are primarily phosphorus (P) or nitrogen (N) limited.
      Plant (15) N fractionation and foliar N : P stoichiometry of a tank epiphyte
      (Vriesea sanguinolenta), and its response to combined N-P fertilization, were
      studied under semi-natural conditions over 334 d to clarify the type of nutrient
      limitation. Plants collected in the field and experimental plants with limited
      nutrient supply showed significant plant (15) N fractionation (mean 50/00) and
      plant N : P ratios of c. 13.5. Higher relative growth rates and declines in plant
      (15) N fractionation (0.50/00) and in foliar N : P ratios to 8.5 in the high N-P
      treatment indicated that these epiphytes were P limited in situ. The critical
      foliar N : P ratio was 10.4, as derived from the breakpoint in the relationship
      between plant (15) N fractionation and foliar N : P. We interpret the widespread
      (15) N depletion of vascular epiphytes relative to their host trees as deriving
      from (15) N fractionation of epiphytes as a result of P limitation. High foliar N
      : P ratios (> 12) corroborate widespread P limitation (or co-limitation by N and
      P) of epiphytic bromeliads and, possibly, other epiphyte species.

PMID- 21729089
TI  - Alternative perspective on intestinal calcium absorption: proposed complementary
      actions of Ca(v)1.3 and TRPV6.
AB  - Transcellular models of dietary Ca(2+) absorption by the intestine assign
      essential roles to TRPV6 and calbindin-D(9K) . However, studies with gene
      knockout mice challenge this view. Something fundamental is missing. The L-type
      channel Ca(v) 1.3 is located in the apical membrane from the duodenum to the
      ileum. In perfused rat jejunum in vivo and in Caco-2 cells, Ca(v) 1.3 mediates
      sodium glucose transporter 1 (SGLT1)-dependent and prolactin-induced active,
      transcellular Ca(2+) absorption, respectively. TRPV6 is activated by
      hyperpolarization and is vitamin D dependent; in contrast, Ca(v) 1.3 is activated
      by depolarization and is independent of calbindin-D(9K) and vitamin D. This
      review considers evidence supporting the idea that Ca(v) 1.3 and TRPV6 have
      complementary roles in the regulation of intestinal Ca(2+) absorption as
      depolarization and repolarization of the apical membrane occur during and between
      digestive periods, respectively, and as chyme moves from one intestinal segment
      to another and food transit times increase. Reassessment of current arguments for
      paracellular flow reveals that key phenomena have alternative explanations within
      the integrated Ca(v) 1.3/TRPV6 view of transcellular Ca(2+) absorption.

PMID- 21729090
TI  - Beyond cholesterol-lowering effects of plant sterols: clinical and experimental
      evidence of anti-inflammatory properties.
AB  - Inflammation is a strong risk factor for cardiovascular disease. Dietary plant
      sterols are known to reduce plasma cholesterol levels and thereby reduce
      cardiovascular risk. Recent observations from animal and human studies have
      demonstrated anti-inflammatory effects of phytosterols. For example, several
      animal and human studies report reductions in the levels of proinflammatory
      cytokines, including C-reactive protein, after consumption of dietary plant
      sterols. Although the cholesterol-lowering effects of phytosterols in humans are
      well documented, studies on the effects of phytosterols on inflammatory markers
      have produced inconsistent results. This review summarizes and discusses findings
      from recent animal and human studies with regard to the potential anti
      inflammatory effects of dietary phytosterols. Findings on the effects of plant
      sterols on inflammation remain limited and confounding. Future research using
      better-designed and well-controlled laboratory studies and clinical trials are
      needed to fully understand the mechanisms through which phytosterols influence
      inflammation. Additional well-designed placebo-controlled studies are needed to
      better understand how and to what extent dietary plant sterols may modify the
      immune system and the production of inflammatory markers.

PMID- 21729091
TI  - Solving the puzzle of attention deficit hyperactivity disorder.

PMID- 21729092
TI  - Artificial food dyes and attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most common
      behavioral disorders in children. Symptoms of ADHD include hyperactivity, low
      frustration tolerance, impulsivity, and inattention. While the biological
      pathways leading to ADHD are not clearly delineated, a number of genetic and
      environmental risk factors for the disorder are recognized. In the early 1970s,
      research conducted by Dr. Benjamin Feingold found that when hyperactive children
      were given a diet free of artificial food additives and dyes, symptoms of
      hyperactivity were reduced. While some clinical studies supported these findings,
      more rigorous empirical studies conducted over the next 20 years were less
      positive. As a result, research on the role of food additives in contributing to
      ADHD waned. In recent years, however, interest in this area has revived. In
      response to more recent research and public petitions, in December 2009 the
      British government requested that food manufacturers remove most artificial food
      dyes from their products. While these strictures could have positive effects on
      behavior, the removal of food dyes is not a panacea for ADHD, which is a
      multifaceted disorder with both biological and environmental underpinnings.

PMID- 21729093
TI  - Human gut microbiota and its relationship to health and disease.
AB  - Probiotics are live microorganisms that confer a health benefit on the host when
      administered in appropriate amounts. Over 700 randomized, controlled, human
      studies have been conducted with probiotics thus far, with the results providing
      strong support for the use of probiotics in the clinical prevention or treatment
      of gastrointestinal tract disorders and metabolic syndrome. The present review is
      based on webinar presentations that were developed by the American
      Gastroenterological Association (AGA) in partnership with the International
      Scientific Association for Probiotics and Prebiotics (ISAPP) and the North
      American branch of the International Life Sciences Institute (ILSI North
      America). The presentations provided gastroenterologists and researchers with
      fundamental and current scientific information on the influence of gut microbiota
      on human health and disease, as well as clinical intervention strategies and
      practical guidelines for the use of probiotics and prebiotics.

PMID- 21729094
TI  - The art of translating nutritional science into dietary guidance: history and
      evolution of the Dietary Guidelines for Americans.
AB  - The United States government has published official Dietary Guidelines for
      Americans (DGA) since 1980 and has recently released the 2010 version. Serving as
      a foundational cornerstone for federal nutrition policy, the DGA embrace current
      nutritional science and translate it into practical guidance to enhance the
      overall health of Americans. This article reviews the history and process for
      developing the DGA, including the incorporation of sophisticated and systematic
      techniques for reviewing emerging evidence. It also explores issues related to
      implementation of the guidelines through federal policy, the food supply, and
      consumer knowledge and behavior.

PMID- 21729095
TI  - Nutrition science mustn't accept a lower level of evidence.

PMID- 21729098
TI  - Red-blood-cell alloimmunization and number of red-blood-cell transfusions.
AB  - BACKGROUND: Patients receiving red-blood-cells may form antibodies against the
      alloantigens expressed by red-blood-cells, with the risk of serious morbidity and
      the need for extensive phenotype-matching in subsequent transfusions. The
      incidence of alloimmunization is considered variable for specific patient groups
      and for first time antibody formation. We therefore studied the cumulative
      incidence of the first formed alloantibody as a function of red-blood-cells
      exposure. METHODS: We performed a new-user cohort among all previously non
      transfused non-alloimmunized patients that received non-extended matched (ABO and
      RhD) red-blood-cells transfusions from January 2005 to December 2009 in our
      university medical centre. Alloimmunization incidences were estimated by Kaplan
      Meier survival-analysis. RESULTS: A total of 3002 previously non-transfused
      patients received 31103 red-blood-cell units. A first time alloantibody forming
      event was experienced by 54 (1.8%) patients. The cumulative incidence of
      alloimmunization was 1.0% at 5 units, 2.4% at 10 units, 3.4% at 20 units and 6.5%
      at 40 units of red-blood-cells transfused. CONCLUSION: The risk to develop a
      first red-blood-cells alloantibody increases up to the 40th transfusion and is
      similar for men and women. More data are needed to examine the risk after 40th
      transfusion.

PMID- 21729099
TI  - Molecular basis of the rare gene complex, DIVa(C)-, which encodes four low
      prevalence antigens in the Rh blood group system.
AB  - BACKGROUND: Over 40 years ago, an unusual Rh phenotype denoted DIVa(C)- was
      identified in a case of fatal haemolytic disease of the newborn in the third
      child of Madame Nou. Her RBCs expressed a partial D, weak C and four low
      prevalence Rh antigens: Go(a) (RH30), Rh33 (RH33), Riv (RH45) and FPTT (RH50).
      The purpose of this study was to determine the molecular basis associated with
      this rare DIVa(C)- complex. MATERIAL AND METHODS: Blood samples were from three
      donors previously identified as carrying the DIVa(C)- haplotype. Molecular
      analyses were performed by standard methods. RESULTS: The three donors were
      heterozygous for RHD and RHD*DIVa.2, and all carried a compound hybrid allele at
      the RHCE locus. This hybrid RHCE allele contained exons 2 and 3 from RHD*DIVa.2
      and exon 5 from RHD [RHCE*CE-DIVa.2(2-3)-CE-D(5)-CE] and is in cis to RHD*DIVa.2.
      The RHCE allele on the in trans chromosome differs between the donors and is
      RHCE*cE in donor 1, RHCE*ce (254C, 733G) in donor 2 and RHCE*ce in donor 3.
      CONCLUSIONS: The RHD*DIVa.2 encodes the Go(a) antigen, whereas the compound
      hybrid allele most likely encodes Rh33, Riv and FPTT. The weakly expressed C
      antigen on RBCs with the DIVa(C)- phenotype could be encoded by exons 2 and 3
      from RHD*DIVa.2 in the compound hybrid. This is the first report of RHD*DIVa.2
      being involved in a hybrid gene at the RHCE locus. As only one example of anti
      Riv has been described, our molecular analysis and findings provide a tool by
      which to predict Riv expression.

PMID- 21729100
TI  - Effect of cholesterol and CYP46 polymorphism on cognitive event-related
      potentials.
AB  - The integrated effect of the cholesterol and CYP46 genotypes on the risk of
      cognitive decline needs to be determined. Using the Cognitive Abilities Screening
      Instrument (CASI), 145 mentally healthy middle-aged and older adults were
      recruited to investigate the influence of cholesterol and CYP46 genotypes on
      cognitive event-related potentials (ERPs). The subjects with a high low-density
      lipoprotein cholesterol (LDL-C) level displayed significantly lower amplitude
      ERPs, although the CASI scores showed no difference. There was no association
      between the CYP46 genotypes, CASI scores, cholesterol levels, and measures of
      ERPs. No interaction between LDL-C level and CYP46 genotypes was noted. The LDL-C
      level is an independent predictor of low P300 amplitude. Prevention and treatment
      of high cholesterol may be of potential benefit in reducing cognitive impairment.

PMID- 21729101
TI  - Resting EEG theta power correlates with cognitive performance in healthy older
      adults.
AB  - We address the degree to which resting EEG bandpower is associated with cognitive
      performance in 73 healthy older adults (aged 56-70). Relative theta (4-6.5 Hz)
      power was significantly correlated with immediate and delayed verbal recall,
      attention, and executive function measures. Relative delta and alpha power and
      peak alpha frequency did not correlate with any cognitive measures. These data
      indicate that high resting theta power in healthy older adults is associated with
      better cognitive function and may be a marker of healthy neurocognitive aging.
      Comparison of these with previous findings suggests that two forms of theta
      frequency oscillations may exist; one indicative of healthy neurocognitive
      function and the other, EEG/alpha slowing linked to (future) substantial
      cognitive decline. Future EEG investigations of cognitive aging or decline should
      analyze both relative theta power and degree of EEG/alpha slowing so as not to
      confound these.

PMID- 21729102
TI  - Responsibility modulates neural mechanisms of outcome processing: an ERP study.
AB  - The role of personal responsibility in decision-making and its influence on the
      outcome evaluation process have been investigated relatively rarely in cognitive
      neuroscience. The present event-related brain potential (ERP) study manipulated
      the subjective sense of responsibility by modifying outcome controllability in a
      gambling task. Participants reported a higher sense of responsibility and
      produced a larger fERN when they were told that the game was 'controllable'
      compared with when they were told that the game was 'uncontrollable.' In
      addition, fERN amplitude was correlated with individual self-reports of personal
      responsibility over the outcomes. These results indicate that self-attribution of
      responsibility associated with different degrees of controllability affects the
      outcome evaluation process and fERN amplitude.

PMID- 21729103
TI  - Pre-ejection period reactivity and psychiatric comorbidity prospectively predict
      substance use initiation among middle-schoolers: a pilot study.
AB  - Youth with conduct problems (CPs) or depression are at high risk for early
      initiation of substance use, and for future substance use disorders (SUDs).
      Comorbid CPs and depression increase risk even further, yet understanding how
      these conditions interact remains elusive. One hypothesis is that altered
      mesolimbic dopamine function contributes to symptoms of CPs, depression, and
      SUDs. Cardiac pre-ejection period (PEP) reactivity to incentives is linked
      theoretically and functionally to central dopamine responding. We evaluated PEP
      reactivity to reward as a prospective biomarker of substance use in a study of
      206 youth with depression, CPs, CPs and depression, or no psychiatric condition.
      Children were 8-12 years old at the first of three annual assessments. Reduced
      PEP reactivity was associated with increased likelihood of future alcohol use,
      and CPs interacted with anxiety and depression to double risk for marijuana and
      other substance use.

PMID- 21729104
TI  - Arousal modulation of memory and amygdala-parahippocampal connectivity: a PET
      psychophysiology study in specific phobia.
AB  - Phobic fear is accompanied by intense bodily responses modulated by the amygdala.
      An amygdala moderated psychophysiological measure related to arousal is
      electrodermal activity. We evaluated the contributions of electrodermal activity
      to amygdala-parahippocampal regional cerebral blood flow (rCBF) during phobic
      memory encoding in subjects with spider or snake phobia. Recognition memory was
      increased for phobia-related slides and covaried with rCBF in the amygdala and
      the parahippocampal gyrus. The covariation between parahippocampal rCBF and
      recognition was related to electrodermal activity suggesting that parahippocampal
      memory processes were associated with sympathetic activity. Electrodermal
      activity further mediated the amygdala effect on parahippocampal activity. Memory
      encoding during phobic fear therefore seems contingent on amygdala's influence on
      arousal and parahippocampal activity.

PMID- 21729105
TI  - Pharmacokinetics and pharmacodynamic effects of meloxicam in piglets subjected to
      a kaolin inflammation model.
AB  - The pharmacokinetics and the analgesic, anti-inflammatory and antipyretic effects
      of meloxicam were investigated in a placebo controlled study in 2-week-old
      piglets. Inflammation was induced by a subcutaneous injection of kaolin in the
      left metacarpus, and 16 h later, meloxicam (0.6 mg/kg) or saline was administered
      intramuscularly. The absorption half-life was relatively short (0.19 h) and the
      elimination half-life was 2.6 h. Mechanical nociceptive threshold testing was
      used to evaluate the analgesic effect, but no significant effect of the meloxicam
      treatment was found. The skin temperature of the inflamed area increased after
      the kaolin injection, but no significant decrease in temperature was found after
      administration of meloxicam. Only limited pyresis was observed after the kaolin
      injection, and no significant antipyretic effect of meloxicam was found. The
      results indicated that this dose of meloxicam had very limited anti-inflammatory
      and analgesic effects in piglets.

PMID- 21729106
TI  - Interleukin 4, interleukin 4 receptor-alpha and interleukin 10 gene polymorphisms
      in Chagas disease.
AB  - In this study, we investigated the association between single-nucleotide
      polymorphisms (SNPs) of the interleukin-4 (IL4), interleukin-4 receptor-alpha
      (IL4RA) and interleukin-10 (IL10) genes with the development of chagasic heart
      disease. This study included 260 patients from Colombia who were serologically
      positive for Trypanosoma cruzi antigens (cardiomyopathic, n=130; asymptomatic,
      n=130). Genotypes were determined by polymerase chain reaction (PCR)-restriction
      fragment length polymorphism or sequence-specific primer methods. We found
      statistically significant differences in the distribution of the IL4RA +148 AA
      (P=0.025, OR=1.89, CI=1.04-3.43) genotype when comparing asymptomatic and
      symptomatic patients. No statistically significant differences in the genotype
      and allele frequency of IL4 and IL10 gene polymorphisms between symptomatic and
      asymptomatic patients were observed. Our experimental evidence suggests that the
      IL4RA +148 AA genotype has a weak association with the development of chagasic
      cardiomyopathy in the population under study.

PMID- 21729107
TI  - High concentration of adenosine in human visceral leishmaniasis despite increased
      ADA and decreased CD73.
AB  - Absence of an effective Th-1 response has been demonstrated as a major cause for
      the disease pathology among patients with visceral leishmaniasis (VL). Defining
      strategies to prevent the development of Th-2 response and/or initiate/activate
      effective Th-1 response may be of help to reduce the growing incidence of drug
      unresponsiveness. Adenosine, which is considered as an endogenous anti
      inflammatory agent is generated in injured/inflamed tissues by the enzymatic
      catabolism of adenosine triphosphate (ATP), and it suppresses inflammatory
      responses of essentially all immune cells. The extracellular adenosine-producing
      pathway comprises two major enzymes CD39 (ATP -> ADP -> AMP) and CD73 (AMP ->
      Adenosine). In contrast, the adenosine-degrading pathway contains only one major
      enzyme adenosine deaminase (ADA). Our study shows high concentration of adenosine
      in diseased condition, varying expression of enzyme involved in adenosine
      producing (CD73?) and adenosine-degrading (ADA?) pathways. These are less studied
      in infections like VL but are very important in terms of endogenous regulation of
      immune response among patients.

PMID- 21729108
TI  - Combinatorial events of insertion sequences and ICE in Gram-negative bacteria.
AB  - The emergence of antibiotic and antimicrobial resistance in Gram-negative
      bacteria is incremental and linked to genetic elements that function in a so
      called 'one-ended transposition' manner, including ISEcp1, ISCR elements and Tn3
      like transposons. The power of these elements lies in their inability to
      consistently recognize one of their own terminal sequences, while recognizing
      more genetically distant surrogate sequences. This has the effect of mobilizing
      the DNA sequence found adjacent to their initial location. In general, resistance
      in Gram-negatives is closely linked to a few one-off events. These include the
      capture of the class 1 integron by a Tn5090-like transposon; the formation of the
      3' conserved segment (3'-CS); and the fusion of the ISCR1 element to the 3'-CS.
      The structures formed by these rare events have been massively amplified and
      disseminated in Gram-negative bacteria, but hitherto, are rarely found in Gram
      positives. Such events dominate current resistance gene acquisition and are
      instrumental in the construction of large resistance gene islands on chromosomes
      and plasmids. Similar combinatorial events appear to have occurred between
      conjugative plasmids and phages constructing hybrid elements called integrative
      and conjugative elements or conjugative transposons. These elements are beginning
      to be closely linked to some of the more powerful resistance mechanisms such as
      the extended spectrum beta-lactamases, metallo- and AmpC type beta-lactamases.
      Antibiotic resistance in Gram-negative bacteria is dominated by unusual
      combinatorial mistakes of Insertion sequences and gene fusions which have been
      selected and amplified by antibiotic pressure enabling the formation of extended
      resistance islands.

PMID- 21729109
TI  - Fungal development of the plant pathogen Ustilago maydis.
AB  - The maize pathogen Ustilago maydis has to undergo various morphological
      transitions for the completion of its sexual life cycle. For example, haploid
      cells respond to pheromone by forming conjugation tubes that fuse at their tips.
      The resulting dikaryon grows filamentously, expanding rapidly at the apex and
      inserting retraction septa at the basal pole. In this review, we present progress
      on the underlying mechanisms regulating such defined developmental programmes.
      The key findings of the postgenomic era are as follows: (1) endosomes function
      not only during receptor recycling, but also as multifunctional transport
      platforms; (2) a new transcriptional master regulator for pathogenicity is part
      of an intricate transcriptional network; (3) determinants for uniparental
      mitochondrial inheritance are encoded at the a2 mating-type locus; (4)
      microtubule-dependent mRNA transport is important in determining the axis of
      polarity; and (5) a battery of fungal effectors encoded in gene clusters is
      crucial for plant infection. Importantly, most processes are tightly controlled
      at the transcriptional, post-transcriptional and post-translational levels,
      resulting in a complex regulatory network. This intricate system is crucial for
      the timing of the correct order of developmental phases. Thus, new insights from
      all layers of regulation have substantially advanced our understanding of fungal
      development.

PMID- 21729110
TI  - Cancer 'survivor-care': I. the alpha7 nAChR as potential target for chemotherapy
      related cognitive impairment.
AB  - WHAT IS KNOWN AND OBJECTIVE: Far more patients are now surviving cancer than ever
      before because of major advances in the diagnosis and treatment of primary and
      metastatic malignancy. Adjuvant chemotherapeutic drug and combination regimens
      have contributed to the success. However, persistent residual adverse effects
      involving mild impairment of cognitive impairment have been reported. Our
      objective is to review and to comment on the basic science and clinical evidence
      of potential pharmacologic targets for managing this emerging concern. COMMENT: A
      search was conducted of basic science and clinical literature related to the
      objective and the information obtained was organized and evaluated from the
      perspective of its insight into potential pharmacotherapeutic targets. A large
      body of evidence suggests that the nicotinic acetylcholine receptor (nAChR), and
      in particular the alpha7 subtype, is involved in memory and that agonists and
      positive allosteric modulators of this receptor have potential in schizophrenia
      and Alzheimer animal models and patients. WHAT IS NEW AND CONCLUSION: We identify
      significant indirect evidence that the selective alpha7 nAChR drugs that are
      currently being investigated for cognitive improvement in schizophrenia and
      Alzheimer disease patients may be useful in cancer chemotherapy-related cognitive
      impairment. The clinical use of those drugs should be explored.

PMID- 21729111
TI  - Guidelines for the management of chronic medication in the perioperative period:
      systematic review and formal consensus.
AB  - WHAT IS KNOWN AND OBJECTIVE: The worldwide volume of surgery is huge and the
      number of interventions performed is increasing as a result of advances in
      technological resources and refinement of medical teams' expertise, in a
      progressively elderly and sick population. Consequently, half of the general
      surgical patients take medications unrelated to surgery. Evidence-based
      guidelines for perioperative medication management are therefore critically
      needed to improve safety in surgery. The purpose of this work was to develop
      practice recommendations for the management of chronic medication in the
      perioperative period. METHODS: A systematic review and a formal consensus were
      performed. A search in Medline, Embase, ISI Web of Knowledge and Medscape were
      conducted in September 2008. Two independent investigators assessed the quality
      of selected studies. Evidence-based guidelines with strength classification were
      found for some therapeutic groups. Those guidelines were adopted and no further
      analysis was performed. For the other therapeutic groups, a formal consensus was
      used, based on a modified nominal group technique: 32 statements were formulated
      considering the literature retrieved. A selected panel of experts was asked by
      electronic mail to rate their level of agreement with each statement. Then, a
      meeting was convened and a second round survey was used to determine the final
      level of agreement. The statements which met the established criteria of
      consensus were developed into practice recommendations, supported by the results
      of the formal consensus and the evidence-based findings from systematic review.
      RESULTS AND DISCUSSION: A total of 23 studies were included in the systematic
      review; three randomized controlled trials (RCTs), 13 cohorts, two case-controls
      and three clinic-cases. Twenty-two practice recommendations for the management of
      chronic medication in the perioperative period resulted from formal consensus.
      WHAT IS NEW AND CONCLUSION: Epidemiological studies concerning the perioperative
      management of chronic medications are clinically heterogeneous and there are few
      RCTs available. However, the formal consensus method proved to be a helpful tool
      to integrate different strands of evidence for the development of practice
      guidelines.

PMID- 21729112
TI  - Appropriate medication prescribing in elderly patients: how knowledgeable are
      primary care physicians? A survey study in Parma, Italy.
AB  - WHAT IS KNOWN AND OBJECTIVE: Increasing attention is being paid to inappropriate
      medication prescribing for the elderly. A growing body of studies have detected a
      prevalence of inappropriate prescribing ranging from 12% to 40% worldwide,
      including Regione Emilia-Romagna, Italy. To improve quality of prescribing, a
      multi-phase pilot project in the Local Health Unit (LHU) of Parma, Regione Emilia
      Romagna, was established. This phase aimed to assess primary care physicians'
      knowledge of appropriate prescribing in elderly patients. METHODS: In total, 155
      primary care physicians (51% of the total), convened by the LHU of Parma for an
      educational session, were asked to complete anonymously a 19-item paper survey.
      Knowledge of inappropriate medication use in the elderly was assessed using seven
      clinical vignettes based on the 2002 Beers Criteria. Topics tested included
      hypertension, osteoarthritis, arrhythmias, insomnia and depression. Data
      regarding physician's perceived barriers to appropriate prescribing for elderly
      patients were also collected. To evaluate the relationship between physician
      knowledge scores and physician characteristics, physicians were classified as
      having a 'low score' (three or below) or a 'high score' (six or more) with
      respect to their knowledge of prescribing for the elderly. RESULTS AND
      DISCUSSION: All physicians completed the survey. Most physicians (88%) felt
      confident in their ability to prescribe appropriate medications for the elderly.
      Thirty-nine physicians (25%) received a 'high score' compared to 26 (17%) who
      received a 'low score'. 'Lower score' respondents had been in practice for a
      longer time (P < 0.05) than 'higher score' respondents. Perceived barriers to
      appropriate prescribing included potential drug interactions (79% of respondents)
      and the large number of medications a patient is already taking (75%). WHAT IS
      NEW AND CONCLUSION: The study results show an unsatisfactory knowledge of
      appropriate prescribing among primary care physicians in the LHU of Parma,
      especially among older physicians. Educational strategies tailored to primary
      care physicians should be establish to enhance knowledge in this area and improve
      quality of prescribing.

PMID- 21729113
TI  - The need for better data about counterfeit drugs in developing countries: a
      proposed standard research methodology tested in Chennai, India.
AB  - WHAT IS KNOWN AND OBJECTIVE: There is still surprisingly little basic research
      data to support widely repeated claims about the prevalence of drug
      counterfeiting. To meet the need for more reliable drug quality data, we designed
      a study framework that includes clear definitions of measured end points,
      sampling methods and assay technique. Our objective was to test this research
      design in Chennai (formerly Madras), India, using a joint Indian and Canadian
      team. METHODS: The city was divided into ten areas along municipal lines. From
      each area, ten stores and pharmacies selling drugs were selected. At each of
      these 100 outlets, three study drugs (artesunate, ciprofloxacin and rifampicin)
      were purchased. The 300 samples were tested by Liquid Chromatography-Mass
      Spectrometry. Assay content was expressed as a percentage of stated tablet
      content. Based on assay results and their distribution, we developed drug quality
      definitions for normal manufacturing standards, counterfeiting, decomposition,
      poor quality control and adulteration. RESULTS: The group mean for ciprofloxacin
      was close to normal manufacturing limits (99.2 +/- 7.1%) but rifampicin (91.6 +/-
      5.7%), and artesunate (80.1 +/- 9.1%), were both below normal pharmaceutical
      standards. Overall, 43% of all samples fell below the widely accepted
      manufacturing range of 90-110% of stated content. No tablet from any sample
      contained less than 50% of the stated dose. WHAT IS NEW AND CONCLUSION: The
      quality of at least some anti-infective drugs in Chennai is below commonly
      accepted standards but we found no evidence of criminal counterfeiting. Poor drug
      quality was most likely due to decomposition during storage or poor manufacturing
      standards. Our research methodology worked well under practical conditions and
      should hopefully be of value to others working in this area.

PMID- 21729114
TI  - In vitro inhibitory effects of Wen-pi-tang-Hab-Wu-ling-san on human cytochrome
      P450 isoforms.
AB  - WHAT IS KNOWN AND OBJECTIVE: Although Wen-pi-tang-Hab-Wu-ling-san (WHW), an
      oriental herbal medicine, has been prescribed for the treatment of chronic renal
      failure (CRF) in Korean clinics, no studies regarding WHW-drug interactions had
      been reported. The purpose of this study was to evaluate the possibility that WHW
      inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.
      METHODS: The abilities of various WHW extracts to inhibit phenacetin O-de
      ethylation (CYP1A2), tolbutamide 4-methylhydroxylation (CYP2C9), omeprazole 4'
      hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone
      6-hydroxylation (CYP2E1) and midazolam 1-hydroxylation (CYP3A4) were assessed
      using human liver microsomes. RESULTS AND DISCUSSION: WHW extract at
      concentrations up to 100 MUm showed negligible inhibition of the six CYP isoforms
      tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC(50)
      values (concentration of the inhibitor causing 50% inhibition of the original
      enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 MUg/mL,
      respectively. WHAT IS NEW AND CONCLUSION: Our in vitro findings suggest that WHW
      extract at concentrations corresponding to a clinically recommended dosage range
      has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW
      extract may be free of drug-herb interactions when co-administered with other
      medicines. However, in vivo human studies are needed to confirm these results.

PMID- 21729115
TI  - A learning-based approach for performing an in-depth literature search using
      MEDLINE.
AB  - WHAT IS KNOWN AND OBJECTIVE: Exhaustive literature searching is a core
      requirement for developing guidelines for evidence-based practice. MEDLINE is
      typically used. Searching requires the user to identify appropriate search terms,
      called Medical Subject Headings (MeSH) and refine the search to retrieve relevant
      articles. The objective of this study was to develop and test a learning
      algorithm for conducting a thorough literature search. METHODS: A learning
      algorithm to effectively utilize MeSH terms is presented. This algorithm creates
      combinations of available MeSH terms from which a search is conducted. The
      algorithm was applied to search MEDLINE (January 1950 to Janaury 2008) focusing
      on the impact of pharmaceutical care in HIV-infected patients. The number of
      relevant articles retrieved from the learning algorithm search was then compared
      against a static search with a fixed set of keywords implemented by an
      independent user. RESULTS AND DISCUSSION: The learning algorithm retrieved 1670
      articles with six relevant articles identified. The static search retrieved a
      total of 49 articles, with three being relevant. These three articles were also
      located from the learning algorithm-based search. WHAT IS KNOWN AND CONCLUSION:
      Performing a literature search for retrieving evidence-based studies can be a
      daunting and error-prone process. The introduction of automatic, learning tools
      for searching is desirable and we present a possible approach.

PMID- 21729116
TI  - Pupillometry in healthy volunteers as a biomarker of tramadol efficacy.
AB  - WHAT IS KNOWN AND OBJECTIVE: The opioid effect of tramadol, which can be detected
      by pupillary response, is predominantly mediated by the O-demethylated
      metabolite, formed via CYP2D6. This study was designed to evaluate the effects of
      tramadol using different parameters of pupillometry as biomarkers. METHODS: Sixty
      nine healthy volunteers received tramadol hydrochloride drops orally at a dose of
      0.7 mg/kg. Pre-dose and 2-h post-dose pupillometric measurements were performed.
      The polymorphism of CYP2D6 was analysed. RESULTS AND DISCUSSION: Large
      interindividual variability was observed in the tramadol-induced pupillary
      reaction. Miosis was induced in 69.6% and mydriasis in 30.4% of the subjects. The
      pupillary response differed in relation to the CYP2D6 genotype. A maximal
      difference in initial pupil diameter of 0.81 mm was found in extensive
      metabolizers. There were significant effects observed on the pupillary light
      reflex parameters with tramadol administration (P < 0.05) except for the reflex
      amplitude and constriction velocity. WHAT IS NEW AND CONCLUSION: The
      pharmacodynamic effects of tramadol were easily detected using both static and
      dynamic pupil parameters. The pharmacodynamic profiles were markedly influenced
      by the CYP2D6 phenotype.

PMID- 21729117
TI  - Beneficial response to gabapentin portraying with interval change of brain SPECT
      imaging in a case with failed back surgery syndrome.
AB  - WHAT IS KNOWN AND OBJECTIVE: Failed back surgery syndrome (FBSS) is a well
      recognized consequence of surgery of the lumbar spine. Here, we present a case
      with FBSS associated neuropathic pain. CASE SUMMARY: During hospital stay, the
      patient was stabilized with gabapentin 200 mg twice a day and this was titrated
      to a dose of 1200 mg per day over the period of 1 week. The treatment produced a
      substantial reduction in his episodic pain. We assessed regional cerebral blood
      flow (rCBF) by using brain single photon emission computed tomography (SPECT)
      scans, which were performed before and after gabapentin treatment 1 week later.
      The examination of the first SPECT showed decreased uptake in left fronto
      temporal-parietal region. The latter one showed much improvement of the above
      areas. WHAT IS NEW AND CONCLUSION: The gabapentin has beneficial effect in the
      FBSS associated neuropathic pain. Besides, this case suggests the association
      between rCBF and pain associated with FBSS, as well as the association of
      gabapentin and altered blood flow of brain cortex.

PMID- 21729118
TI  - Experiences of children/young people and their parents, using insulin pump
      therapy for the management of type 1 diabetes: qualitative review.
AB  - WHAT IS KNOWN AND OBJECTIVE: Advances in medical technology have made insulin
      pumps an attractive treatment option for patients with type 1 diabetes and in
      particular for children and young people. Previous studies have accounted the
      experiences and views of children/young people and their parents for the use of
      the injection therapy, but very few have focused on the use of insulin pumps. The
      objective of this review was to identify studies that explore the experiences of
      children/young people and their parents on the transition from injections to
      insulin pump therapy, in the context of their social life. METHODS: A systematic
      literature search was conducted, and six studies meeting the inclusion and
      exclusion criteria were identified. RESULTS:   Views and perspectives from the
      studies identified mainly focused on: introduction to the pump; reasons for the
      transition to pump therapy; advantages and disadvantages of this treatment
      option; and impact on quality of life (QoL). Parents and/or children reported
      that they learned about pump therapy either formally from a healthcare
      professional or informally from a friend or the internet. Many reasons were
      identified for the transition, the most important being the pursuit of stable and
      controlled blood sugar levels and the desire for a more flexible lifestyle.
      Participants highlighted the advantages of insulin pumps in terms of improved
      diabetes control. Moreover, there was a positive impact on the QoL, as insulin
      pumps provided children greater flexibility in lifestyles especially with regards
      to meals and socialization. In contrast, psychosocial issues such as pump
      visibility and physical restrictions were highlighted as disadvantages. Issues
      such as day-to-day management were also discussed. WHAT IS NEW AND CONCLUSION:
      Exploring children/young people's perspectives on the use of pump therapy for
      managing their diabetes, and parental reflections in caring for those children is
      important as it provides evidence informing policy for the wider implementation
      of this technology in the management of diabetes in children. However, the review
      revealed that there is a scarcity of data in this area and that further research
      is needed.

PMID- 21729119
TI  - Scientific misconduct - how does it affect you?

PMID- 21729120
TI  - In vitro antimicrobial effects of commercially available mouth-wetting agents.
AB  - Products have been developed to provide palliation for persons with dry mouth. In
      addition to mouth-wetting agents, some products incorporate antimicrobial
      constituents with the goal of improving oral microbial defenses. The aim of this
      in vitro study was to investigate the potential antimicrobial and antifungal
      effects of two commercially available saliva substitutes on Streptococcus mutans,
      Lactobacillus acidophilus, and Candida albicans by using the agar-well diffusion
      method. Antimicrobial activity as measured by the size of the inhibition zone
      growth for S. mutans and L. acidophilus was observed only with Biotene Dry Mouth
      Oral Rinse(r) and BioXtra(r) gel. The zone of inhibition of Biotene Dry Mouth
      Oral Rinse was larger than that of BioXtra gel (p= 0.00, p < 0.01). No
      anticandidal effect was seen with any of the test products. The pH of the
      preparations, the variations between the amount of active ingredients within the
      products, and the potential antimicrobial effects of inactive ingredients should
      be investigated to determine the factors that impacted microbial inhibition.

PMID- 21729121
TI  - Radiographic changes of the jaws in HbSS and HbSC genotypes of sickle cell
      disease.
AB  - This study used panoramic radiographs to evaluate the presence of radiographic
      changes in the jaws of a population who had sickle cell disease (SCD). The
      authors compared the frequency of findings between subjects with and without SCD.
      Panoramic radiographs of 71 subjects with SCD (36 with HbSS and 35 with HbSC) and
      52 healthy controls (HbAA) were evaluated for the presence of the following
      radiographic alterations: radiopaque areas, increased spacing of bony trabeculae,
      horizontal arrangement of bony trabeculae, and absence of mandibular canal
      corticalization. The control group had a significantly smaller number of all the
      radiographic features evaluated. Differences were not statistically significant
      between the groups with HbSS and HbSC, except for more trabecular spacing in the
      molar region in the HbSS genotype, suggesting a possible correlation between
      radiographic findings and disease presentation.

PMID- 21729122
TI  - Dental status of patients with mental disorders in a Nigerian teaching hospital:
      a preliminary survey.
AB  - Although individuals with mental disorders are reported to experience dental
      problems similar to the general population, evidence suggests they actually have
      higher risks of dental disease and increased oral health needs. This study
      describes the dental status of 105 psychiatric outpatients in a Nigerian
      hospital. Information was obtained from subject interviews, medical records, and
      an oral examination to determine their dental caries and periodontal disease
      status. The oral hygiene status of the study participants was poor; the mean oral
      hygiene index score was 2.7 +/- 1.20. The decayed, missing, and filled teeth
      ranged from 0 to 9 with a mean of 2.3 +/- 2.28. Only five subjects (4.9%) had
      restorations and the mean number of filled teeth was .14 +/- .67. The subjects'
      age was significantly related to the mean oral hygiene score (p= .005), the mean
      gingival score (p= .006), and caries occurrence (p= .047). The oral health status
      of psychiatric patients in Nigeria is poor, indicating the need to provide oral
      health education and increase access to dental care for these patients.

PMID- 21729123
TI  - Use of a single implant to retain a mandibular complete overdenture on the
      compromised atrophic alveolar ridge: a case report.
AB  - This case report illustrates some of the advantages gained by placing a single
      implant in the midline of the intersym-physeal region of the mandible, which can
      be used to retain a complete mandibular overdenture in patients with a
      compromised atrophic mandible opposing a maxillary complete denture. This
      approach is a valid treatment option for patients with limited financial and
      therapeutic means. This case report, along with other evidence, demonstrates that
      a mandibular single implant-retained overdenture is a viable treatment option for
      a specific group of patients.

PMID- 21729125
TI  - Iodine deficiency in industrialized countries.

PMID- 21729126
TI  - Trichomonas vaginalis as a rare cause of male factor infertility at a hospital in
      East Anatolia.
AB  - Trichomonas vaginalis is known as an important cause of sexually transmitted
      infection in developing countries. The prevalence and spectrum of Trichomonasis
      in men are less characterised. We analysed the presence of T. vaginalis in 80
      infertile men using wet mount microscopy, Giemsa staining, culture and PCR
      methods. We found 2.5% positivity for T. vaginalis using PCR method. Wet mount
      microscopy was ineffective. Giemsa staining and culture tests were positive only
      in one patient. Both of our PCR-positive patients were symptomatic. Our findings
      suggest that T. vaginalis should be considered for the aetiology of male factor
      infertility, although it is rare in developed countries.

PMID- 21729127
TI  - Evaluation of semen quality in patients with malignancies referred for sperm
      banking before cancer treatment.
AB  - Different cancer treatments such as chemotherapy and radiotherapy can lead to
      azoospermia and even sterility for an unknown period. Whether the type of cancer
      could affect semen quality or not is under debate. In this study, we have
      reviewed semen parameters of men with cancer who deposited their sperm samples at
      the Avicenna Research Institute tissue bank before undergoing cytotoxic
      treatment. This descriptive retrospective study examined 73 cases referred to
      sperm bank, because of malignancy, prior to initiation of cancer treatments
      including chemotherapy and radiotherapy. The data recorded were age, marital
      status, reproductive history, semen analysis reports and cancer history of the
      patients. Semen samples were analysed according to recommendations of the World
      Health Organization (1999) before freezing. Results of the analysis showed that
      71.2% (52) of patients had oligozoospermia, 93.2% (68) teratozoospermia and 86.3%
      (63) asthenozoospermia. Different groups of cancer patients did not show any
      differences in oligozoospermia, teratozoospermia and asthenozoospermia. Impaired
      spermatogenesis even prior to cancer treatment indicates the importance of
      fertility preservation. As the majority of patients had suitable specimens for
      freezing and assisted reproduction, sperm banking is recommended to be performed
      promptly and before any treatment, especially surgery.

PMID- 21729128
TI  - Prevalence of ejaculatory disorders in urban men: results of a random-sample
      survey.
AB  - We aimed to determine the prevalence of early ejaculation disorders (EED) and to
      calculate the prevalence of lifelong premature ejaculation (PE) in Greek urban
      men. Associations with physiological and psychological conditions, treatment
      seeking and treatment efficacy were defined. We surveyed 522 urban men aged 16-62
      individually using an open, one-on-one questionnaire. A total of 305 (58.43%)
      participants reported EED. The prevalence of lifelong PE, according to the
      International Society for Sexual Medicine criteria, was calculated as 17.7%.
      Among sufferers of EED, unrelated stress was the most frequent comorbidity
      (42.6%) and, along with erectile dysfunction and lower urinary tract symptoms,
      occurred more frequently than in normal participants (P < 0.05). Half (50.3%) of
      the sufferers believed that their problem was psychological, while 69.5% never
      sought help. Most (69.2%) of those who did seek help sought it anonymously
      through the internet. Behavioural treatment was preferred to medical treatment.
      Few (13.8%) men were satisfied with their treatment. In conclusion, although the
      observed PE prevalence agrees with the previous findings, more patients suffer
      negative personal and relationship consequences and may also require treatment.
      Most men do not seek medical assistance, and from those who do, most are not
      satisfied with the results of treatment.

PMID- 21729129
TI  - Genotyping of Tunisian azoospermic men with Sertoli cell-only and maturation
      arrest.
AB  - Azoospermia factor (AZF) deletions were associated with severe oligospermia and
      azoospermia with testicular histologies varying from maturation arrest (MA) to
      Sertoli cell-only (SCO) phenotypes. Abnormal androgen receptor (AR) structure or
      function has also been implicated in male infertility. To assess the contribution
      of these genetic defects to azoospermic patients, 19 Tunisian men with SCO (n =
      13) or MA (n = 6) were enrolled in this study. Using immunohistochemistry method,
      we evaluated the expression of AR in testicular biopsy for the two phenotypes.
      PCR with primers flanking the AR-(CAG)n region and direct sequencing were used to
      determine AR-(CAG)n length. And PCR amplification of 14 sequence-tagged sites
      (STSs) located at Yq was used to determine the rate and extent of Y
      microdeletions. We found a significant difference of the AR expression between
      SCO and MA cases. Hence, this expression in the testis depends on the status of
      spermatogenesis. However, we did not find any relationship between the (CAG)
      repeat and the testicular histology (neither for SCO nor MA). On the other hand,
      we found a high frequency of AZF deletions (46.2%) in SCOS and in MA (50%). The
      present results also suggest the contribution of Y chromosome microdeletions in
      SCO and MA pathogenesis.

PMID- 21729130
TI  - Effects of semen processing on the generation of reactive oxygen species and
      mitochondrial membrane potential of human spermatozoa.
AB  - This study was designed to evaluate the effects of semen processing on the
      generation of intracellular reactive oxygen species (ROS) and mitochondrial
      membrane potential (MMP) in spermatozoa, and to develop reliable indexes for the
      evaluation of sperm quality during sperm preparation. Swim-up and density
      gradient centrifugation methods were used to separate semen in
      oligoasthenoteratozoospermia (OAT), leucocytospermia (LC) and normozoospermia
      groups. Levels of ROS and MMP were measured by flow cytometry. Before
      preparation, the patients with abnormal semen parameters had a lower MMP and
      higher ROS, and there was a negative correlation between MMP and ROS. The levels
      of MMP and ROS increased significantly, especially ROS produced by swim-up. A
      significant difference was found between the correlation of MMP and total normal
      motile sperm count after preparation in the OAT group. The level of ROS was
      associated with the amount of white blood cells in the LC group. The MMP can be
      used as an objective index to evaluate the sperm quality of OAT patients, and the
      combination of MMP and ROS can be used to assess the efficiency of sperm
      preparation in LC patients. These findings can guide selection of the ideal sperm
      separation technique for different sperm samples.

PMID- 21729131
TI  - Relationship between chromatin condensation, DNA integrity and quality of
      ejaculated spermatozoa from infertile men.
AB  - Normal chromatin condensation is important for sperm fertilising ability.
      However, routine semen analysis does not identify defects in sperm chromatin
      structure. This study aimed to investigate the condensation of chromatin and DNA
      integrity in spermatozoa of infertile men and deduce the relationship with sperm
      quality, as measured by conventional semen parameters. Semen analysis was carried
      out to assess sperm quality according to World Health Organization criteria. The
      remaining aliquot of each sample was processed for transmission electron
      microscopy, chromomycin A3 (CMA3) and terminal deoxynucleotidyl transferase dUTP
      nick end labelling (TUNEL) assays. The ultrastructural analysis of spermatozoa
      from infertile men showed heterogeneity in sperm nuclear morphology. Some
      spermatozoa displayed a round nucleus with incomplete chromatin condensation.
      Immunoreactivity with antitransitional protein and antiprotamine antibodies
      indicated nuclear maturation defects in the spermatozoa of infertile men.
      Spearman's correlation analysis indicated a positive correlation between the
      percentages of CMA3- and TUNEL-positive spermatozoa. In addition, these two
      parameters were negatively correlated with sperm concentration, motility and
      normal morphology. This study demonstrated that men with morphologically normal
      spermatozoa of <30% have greater degree of protamine deficiency and DNA damage
      than men with morphologically normal spermatozoa of >30%. Evaluation of chromatin
      integrity appears to be a useful tool for assessing male fertility.

PMID- 21729132
TI  - Icarisid II, a PDE5 inhibitor from Epimedium wanshanense, increases cellular cGMP
      by enhancing NOS in diabetic ED rats corpus cavernosum tissue.
AB  - The aim of this study was to explore the effects and mechanisms of Icarisid II
      (ICA-II) on enhancing the cellular cGMP in rat corpus cavernosum tissue (RCCT).
      Diabetes mellitus Wistar rats were induced by streptozotocin, and diabetic ED
      rats were selected for the RCCT culture by apomorphine. ICA-II was extracted and
      purified from Icariin (ICA) by enzymatic method. The RCCT was treated with ICA
      II, ICA and Sildenafil at different concentrations. cGMP and nitric oxide
      synthase (NOS) activities were checked respectively by enzyme immunoassay.
      Meanwhile, nNOS, iNOS and eNOS in RCCT were checked by western blot. ICA-II
      evaluated the intracellular cGMP to 8.01 +/- 1.02 pmol mg(-1) min(-1), which is
      much weaker than that from Sildenafil (12.4 +/- 1.16 pmol mg(-1) min(-1)) (P <
      0.05). There is no significant difference between ICA-II and ICA. With the
      treatment of 10 MUm ICA-II for 24 and 48 h, nNOS expression was significantly
      increased in RCCT (P < 0.05), while the eNOS expression level was very low
      without any change. Notably, ICA-II increased the intracellular NOS activity
      significantly in vitro in RCCT. Except the PDE5 inhibitory effect, ICA-II
      increases the intracellular cGMP through the enhancement of nNOS expression and
      NOS activity in RCCT in vitro. ICA-II implies a potential compound for neurogenic
      erectile dysfunction by NO-cGMP pathway.

PMID- 21729133
TI  - Effects of curcumin and dithioerythritol on frozen-thawed bovine semen.
AB  - The aim of this study was to determine the effects of curcumin and
      dithioerythritol added into bull semen extender on sperm parameters, lipid
      peroxidation, total glutathione and antioxidant potential levels of bull
      spermatozoa following the freeze/thawing process. Twenty-seven ejaculates
      obtained from three bulls were included in the study. Each ejaculate that was
      splitted into five equal groups and diluted in a Tris-based extender containing
      curcumin (0.5 and 2 mM), dithioerythritol (0.5 and 2 mM) and no additive
      (control) was cooled to 5  degrees C and frozen in 0.25-ml French straws. The
      extender supplemented with 0.5 mMdose of curcumin led to lower percentage of
      total abnormality (20.40 +/- 2.36%) when compared to the control (30.60 +/-
      1.47%, P < 0.05). Curcumin and dithioerythritol at 0.5 mM provided a greater
      protective effect in the membrane functional integrity (54.40 +/- 2.09% and 50.00
      +/- 2.68%), in comparison with control (37.20 +/- 1.77%, P < 0.001).
      Supplementation with antioxidants did not significantly affect the lipid
      peroxidation and antioxidant potential levels, while the maintenance of total
      glutathione levels in curcumin 0.5 mM was demonstrated to be higher than that of
      control, following the freeze/thawing (P < 0.05). Supplementation with these
      antioxidants prior to the cryopreservation process may be recommended to
      facilitate the enhancement of sperm cryopreservation techniques.

PMID- 21729134
TI  - Evaluation of epididymal sperm quality following experimentally induced copper
      poisoning in male rats.
AB  - The trace element copper has been identified as a highly toxic element for
      spermatozoa. Our goal in this study was to assess relationship between copper
      poisoning and semen quality parameters. In this study, sixty male Wistar albino
      rats weighing 200-240 g (3.5-4 months old) were divided into three different
      groups of twenty rats as follows: the first group (Group 100), which was treated
      by gavage with copper sulphate at a dose of 100 mg kg(-1) day(-1) for 8 weeks;
      the second group (Group 200), which received 200 mg kg(-1) day(-1) copper
      sulphate by gavage during experimental period (56 days); and the control group
      (Group C), which received the same volume of distilled water by gavage during
      experimental period. The blood, semen and histopathological samples were obtained
      from five cases of 20 animals of each group every 2 weeks at 2, 4, 6 and 8th
      week. Results showed that sperm concentration, motility and viability in group
      100 and 200 were significantly decreased (P < 0.05) in comparison with group C. A
      significant decrease in sperm concentration, motility and viability indicates the
      possibility of adverse effect of copper poisoning on male fertility. Copper might
      be mediator of the effect of oxidative damage and play an essential role in
      spermatogenesis and male infertility.

PMID- 21729135
TI  - Effect of procaine, pentoxifylline and trolox on capacitation and hyperactivation
      of stallion spermatozoa.
AB  - Reasons for low in vitro fertilisation rates in the horse include the
      difficulties in inducing capacitation and/or hyperactivation of stallion
      spermatozoa. The aim of this study was to analyse the effect of noncapacitating
      and capacitating modified Whitten's (MW) and modified Tyrode's medium (MT) and
      treatment with procaine (5 mmol), pentoxifylline (3.5 mmol) and trolox (120 mmol)
      on motility (CASA), capacitation, acrosomal status, viability and mitochondrial
      membrane potential of stallion spermatozoa (n = 4). While there was no influence
      of MW and MT on sperm motility, a significant increase in the percentage of
      viable-capacitated spermatozoa was observed after incubation in capacitating MW
      (P < 0.05). Pentoxifylline showed no significant effect on the motility pattern
      but increased the proportion of live-capacitated spermatozoa (P < 0.05). Trolox
      had no detectable effect on either capacitation or hyperactivation. Procaine was
      the only agent that induced hyperactivation in terms of a reduced proportion of
      progressively motile spermatozoa, straight line velocity, straightness, linearity
      and beat-cross frequency and an increase in the amplitude of lateral head
      displacement (P < 0.05). The combination of capacitating Whitten's medium and
      procaine showed the best results for the induction of capacitation and
      hyperactivation in stallion spermatozoa; this was possible even after short-term
      incubation.

PMID- 21729136
TI  - Sequential analysis of sperm functional aspects involved in fertilisation: a
      pilot study.
AB  - The development of diagnostic techniques in andrology as a second level of
      approach to the diagnosis of male factor infertility has enthused the focus of
      researchers on the development of a sequential diagnostic programme for these
      men. Semen samples of 78 men form couples undergoing in vitro fertilisation
      therapy were used in the study. The semen samples were used to test sperm
      functional aspects known to interfere with fertilisation. These tests included
      semen profile, DNA integrity, apoptosis, chromatin packaging, acridin orange
      staining, zona binding capacity, zona-induced acrosome reaction (AR). Results
      were correlated with fertilisation outcome. Statistical analyses of the recorded
      data were carried out using a logistic regression analysis model on all sperm
      functional tests. A negative and significant association with the fertilisation
      rates was recorded for DNA damage (r = -0.56; P <= 0.0005). A positive
      significant correlation was recorded between fertilisation rates and sperm with
      normal DNA (r = -0.57, P <= 0.0004), and zona-induced AR (r = 0.33, P <= 0.002).
      Diagnostic andrology can be regarded as a mandatory part of the male factor
      patient's work-up schedule to assist clinicians with the most suitable
      therapeutic modality to follow.

PMID- 21729137
TI  - Methylenetetrahydrofolate reductase C677T polymorphism is not associated with
      male infertility in a South Indian population.
AB  - Previous studies have revealed that genetic factors may be involved in regulating
      the mechanism of infertility, e.g., MTHFR gene polymorphism in the development of
      male infertility. The aim of this study is to examine whether an association
      exists between MTHFR C677T polymorphism and male infertility. The study was
      carried out by means of a PCR-RFLP assay in 206 infertile men and 230 ethnically
      matched controls. The statistical analysis using two-sided Fisher's exact test
      and Pearson chi-squared test showed CT genotype is associated nonsignificantly
      with male infertility (OR = 1.19, 95% CI = 0.71-1.97). Because of the lack of TT
      homozygotes in the controls, a combined odds ratio of CT and TT homozygotes
      against the control has been calculated (OR = 1.36, 95% CI = 0.83-2.22), and the
      same was insignificant. The overall results of the study indicate that MTHFR
      C677T polymorphism is not associated with male infertility.

PMID- 21729138
TI  - Typha capensis (Rohrb.)N.E.Br. (bulrush) extract scavenges free radicals,
      inhibits collagenase activity and affects human sperm motility and mitochondrial
      membrane potential in vitro: a pilot study.
AB  - The biodiversity in South Africa provides more than 30,000 higher plants, of
      which more than 3000 are used by traditional healers to treat diseases. Typha
      capensis (bulrush) is one of the medicinal plants used in South Africa to treat
      male fertility problems. Considering that South African traditional healers have
      been recognised by Law and the health benefits of T. capensis have not been
      scientifically investigated yet, this study aimed at investigating the in vitro
      effects of aqueous extracts from this plant on male reproductive functions. Both
      leaves and rhizomes of T. capensis were dried, infused with distilled water and
      freeze-dried. Motile sperm from 50 men were isolated by swim-up and incubated
      with 1 MUg ml(-1) aqueous extract of Typha rhizome for 1 h at 37  degrees C.
      Vitality, motility, sperm production of reactive oxygen species and mitochondrial
      membrane potential were analysed in the test sample, a control and in the pellet
      from the swim-up. Results showed that the rhizome extract had significant (P <
      0.0001) negative effects on all parameters. The extracts from the leaves and
      rhizomes revealed dose-dependent inhibitory activity for collagenase and free
      radical formation. No inhibitory activity for elastase was found. The inhibitory
      activity for collagenase might indicate possible anti-cancer effects.

PMID- 21729139
TI  - Testicular microlithiasis: analysis of prevalence and associated testicular
      cancer in central-eastern Sicilian andrological patients.
AB  - The aim of this retrospective study was to determine the prevalence of testicular
      microlithiasis (TM) in central-eastern Sicilian men and to evaluate the
      association between TM and testicular tumour or infertility. A total of 1056
      Sicilian patients underwent scrotal US between 2005 and 2010. TM was found in 106
      men with an overall prevalence of 10%; roughly about four times the median
      prevalence reported in the previous studies (0.6-18.1%). Forty men (3.8%) had a
      classic TM, whereas 66 (6.2%) had a limited TM. The prevalence of testicular
      tumour in this cohort was 2.4% (25/1056). At the moment when the testicular
      tumour was diagnosed, 15 patients (60%) had TM. There was a significant
      difference (P < 0.01) between the rate of malignancy in men with TM (15/106;
      14.2%) and that in men without TM (10/950; 1.1%) with an odds ratio = 16. The
      prevalence of TM among infertile patients was 18.8%. These data may relate to an
      increased awareness towards scrotal US examination and/or to the use of more
      sensitive equipments. The elevated rate of testicular malignancy in men with TM
      suggests that this US feature may be regarded as a risk factor for testicular
      tumour.

PMID- 21729140
TI  - Systemic and cavernous plasma levels of neuropeptide Y during sexual arousal in
      healthy males.
AB  - Neuropeptide Y (NPY) has been shown to induce contraction of isolated human
      penile erectile tissue and potentiate the response to noradrenaline. The purpose
      of our study was to measure in the cavernous and systemic blood of healthy male
      volunteers the course of NPY through different stages of sexual arousal. Whole
      blood was drawn simultaneously from the corpus cavernosum and the cubital vein of
      16 healthy male volunteers during penile flaccidity, tumescence, rigidity and
      detumescence. Tumescence and erection were induced by applying audiovisual and
      tactile stimulation. Plasma levels of NPY (given in pmol l(-1)) were determined
      by means of an enzyme-linked immunoassay. NPY significantly decreased in the
      cavernous blood on sexual arousal, when the flaccid penis became tumescent and,
      finally, rigid (F: 88.8 +/- 35.8, T: 62.4 +/- 22.7, R: 62.3 +/- 19.7), and only
      slightly rose in the phase of detumescence (64.8 +/- 23). In the systemic
      circulation, no pronounced alterations in the concentration of NPY were
      registered (F: 64.4 +/- 27, T: 65.8 +/- 19, R: 59.6 +/- 25, D: 67.6 +/- 29.3).
      Our findings are in favour of the hypothesis that NPY could contribute to the
      maintenance of the resting state of cavernous smooth muscle.

PMID- 21729141
TI  - Testosterone administration to adult rats differentially modulates androgen and
      oestrogen receptor-alpha expression in reproductive organs and pituitary.
AB  - Regulation of androgen receptor (AR) and oestrogen receptor alpha (ERalpha)
      expression has direct bearing on the physiology of male reproductive organs. With
      the help of three independent tools of immunohistochemistry, western blotting and
      RT-PCR, AR and ER alpha receptor expression was examined in the testis,
      epididymis, prostate, seminal vesicle and pituitary of adult rats following
      testosterone enanthate (TE, 3 mg/100 MUl of olive oil/rat per week) intervention
      for 15 and 30 days. TE administration reduced AR immunoexpression which coincided
      well with the decline in the receptor protein and transcript levels. In contrast,
      ERalpha was found overexpressed in all the organs. While weights of testis and
      epididymis decreased significantly, those of prostate, seminal vesicle and
      pituitary demonstrated an upward trend. Spermatogenesis was adversely affected
      with decline in number of germ cells per tubule and increased prevalence of germ
      cell apoptosis. Increase in serum and decrease in intra-testicular levels of
      testosterone were found significant (P < 0.001) in both 15 and 30 days treatment
      groups. Serum follicle stimulating hormone declined significantly (P < 0.001) at
      the end of 30 days treatment. Taken together, the above findings indicate that
      the testosterone intervention differentially modulates, AR ERalpha expression,
      which is associated with hypospermatogenesis and increased germ cell apoptosis.

PMID- 21729142
TI  - Enhancement of aphrodisiac activity in male rats by ethanol extract of Kaempferia
      parviflora and exercise training.
AB  - This study aimed to investigate the effects of Kaempferia parviflora extract (KD)
      and exercise training on reproductive function in male rats. Sexually mature
      males were assigned to four groups: control, KD70 (received 70 mg kg(-1) day(-1)
      for 4 weeks), Ex (exercise training for 4 weeks), Ex + KD70 (exercise training
      with KD 70 mg kg(-1) day(-1)). At the end of treatment regimes, sexual behaviours
      including mount latency (ML), mount frequency (MF), ejaculation latency (EL),
      post-ejaculation latency (PEL), number of mount within 30 min (MF(30)) and number
      of ejaculation (NEL) were assessed by a video camera, and fertility was tested by
      natural mating. Results showed that KD had no effect on the weights of
      reproductive organs, liver, kidneys and levator ani muscle. On the other hand,
      the weights of epididymis, seminal vesicles, prostate gland and levator ani
      muscle were significantly increased in the Ex and Ex+KD70 groups. ML and EL were
      shortened in all treatment groups, but PEL was decreased only in KP70 group. Only
      Ex and Ex + KD70 groups exhibited lower MF and higher NEL whilst MF(30) were not
      changed in all groups. None of the treatments altered male fertility. It is
      concluded that KD enhanced sexual motivation whereas exercise training promoted
      both sexual motivation and performance.

PMID- 21729143
TI  - Evaluation of Lama glama semen viscosity with a cone-plate rotational viscometer.
AB  - Llama semen is highly viscous. This characteristic is usually evaluated
      subjectively by measuring the thread formed when carefully pippeting a sample of
      semen. The aims of this study were (i) to objectively determine and analyse llama
      semen viscosity, (ii) to compare semen viscosity between ejaculates of the same
      male as well as between different males, (iii) to study the correlation between
      viscosity and other semen characteristics and (iv) to evaluate the effect of
      collagenase on semen viscosity. Semen viscosity was evaluated using a cone-plate
      Brookfield rotational viscometer. A non Newtonian, pseudoplastic behaviour was
      observed in the 45 semen samples evaluated. Rheological parameters were
      determined obtaining the following results (mean +/- SD): apparent viscosity at
      11.5 s(-1): 46.71 +/- 26.8 cpoise and at 115 s(-1): 12.61 +/- 4.1 cpoise;
      structural viscosity (K) (dyne s cm(-2)): 2.18 +/- 1.4 and coefficient of
      consistency (n): 0.45 +/- 0.1. Statistical differences were found between
      different ejaculates of the same male for structural viscosity and apparent
      viscosity at 11.5 s(-1) (P < 0.01). Correlation was found only between
      coefficient of consistency (n) and sperm concentration (P < 0.01). Significant
      differences for coefficient of consistency (n) and viscosity at 115 s(-1) were
      found between samples incubated with and without collagenase (P < 0.05).

PMID- 21729145
TI  - Treatment of cloth with a fabric softener ameliorates skin dryness.
AB  - Dry skin is a condition characterized by impaired skin barrier function including
      atopic dermatitis and senile eczemas. Fabric softening chemicals (FSC) smoothens
      the surface of fabrics and thus decreases friction with the skin. Scientific
      evaluation of fabric softener on skin dryness is very limited. We evaluated the
      effectiveness and safety of FSC-treated T-shirts in subjects with dry skin. This
      is a randomized double-blind control study that included 40 male volunteers with
      apparent dry skin. Subjects were randomly divided into two groups: 20 men
      received 28 pieces of FSC-treated T-shirts wearing them for 4 weeks, and another
      20 men received non-treated T-shirts. The effect of trial was evaluated by visual
      grading, subjective symptom, stratum corneum water content (SCWC), transepidermal
      water loss (TEWL), and dermoscopic skin surface analysis on days 0, 7, 14 and 28.
      A significant improvement of SCWC was observed in the skin of the shoulder (days
      7-28) and lateral abdomen (day 14) wearing the treated T-shirts, but not in the
      non-treated T-shirts. In a stratified analysis of the low and high SCWC group,
      significant improvement was identified in the low SCWC groups but not in high
      SCWC groups. The visual grading of the shoulder improved significantly in the
      treated T-shirts group. No significant improvement was found in TEWL, dermoscopic
      analysis and subjective symptom in both groups. No remarkable side-effect was
      identified throughout this investigation. Addition of a fabric softener during
      clothes laundering is a potent preventive tool for dry skin.

PMID- 21729146
TI  - Case of diabetic scleredema: diagnostic value of magnetic resonance imaging.
AB  - We report the case of a patient with a 20-year history of diabetes mellitus type
      2 who developed sclerotic skin lesions on his neck and upper back. Physical and
      histological findings were compatible with diabetic scleredema. T(2)-weighted
      magnetic resonance imaging (MRI) revealed diffuse thickening of the dermis and
      subcutaneous tissue, with hyperintense signals. The MRI findings in the dermis
      corresponded with the accumulation of collagen tissue with deposition of
      glycosaminoglycans.

PMID- 21729147
TI  - A novel case of nocardiosis with skin lesion due to Nocardia araoensis.
AB  - Nocardiosis is caused by gram-positive aerobic actinomycetes that live in soil
      and are known to be responsible for opportunistic infections. The condition
      mostly affects the lung, brain or skin. Here, we present a 24-year-old Japanese
      woman who had had systemic lupus erythematosus since the age of 20 years, and
      lupus nephritis since the age of 23 years. She developed cutaneous lymph duct
      type nocardiosis due to Nocardia araoensis while on immunosuppressant therapy.
      The patient had cutaneous findings from the right inguinal region to the right
      lower thigh and did not have lesions on the rest of the body. Minocycline and co
      trimoxazole were co-administrated, and her condition improved. To our knowledge,
      this is the first case in which N. araoensis was detected by analysis on rRNA
      base sequence in skin lesions.

PMID- 21729148
TI  - Use of principal component analysis in the evaluation of adherence to statin
      treatment: a method to determine a potential target population for public health
      intervention.
AB  - The prevalence of statin use is high but adherence low. For public health
      intervention to be rational, subpopulations of nonadherent subjects must be
      defined. To categorise statin users with respect to patterns of reimbursement,
      this study was performed using the main French health reimbursement database for
      the Aquitaine region of south-western France. The cohort included subjects who
      submitted a reimbursement for at least one delivery of a statin (index) during
      the inclusion period (1st of September 2004-31st of December 2004). Indicators of
      adherence from reimbursement data were considered for principal component
      analysis. The 119,570 subjects included and analysed had a sex ratio of 1.1, mean
      (SD) age of 65.9 (11.9), and 13% were considered incident statin users. Principal
      component analysis found three dimensions that explained 67% of the variance.
      Using a K-means classification combined with a hierarchical ascendant
      classification, six groups were characterised. One group was considered
      nonadherent (10% of study population) and one group least adherent (1%). This
      novel application of principal component analysis identified groups that may be
      potential targets for intervention. The least adherent group appears to be one of
      the most appropriate because of both its relatively small size for case review
      with prescribing physicians and its very poor adherence.

PMID- 21729150
TI  - Learning from rural health research in other countries.

PMID- 21729151
TI  - Socioeconomic status and injury in a cohort of Saskatchewan farmers.
AB  - PURPOSE: To estimate the strength of relationships between socioeconomic status
      and injury in a large Canadian farm population. METHODS: We conducted a
      prospective cohort study of 4,769 people from 2,043 farms in Saskatchewan,
      Canada. Participants reported socioeconomic exposures in 2007 and were followed
      for the occurrence of injury through 2009 (27 months). The relative hazards of
      time to first injury according to baseline socioeconomic status were estimated
      via Cox proportional hazards models. FINDINGS: Risks for injury were not
      consistent with inverse socioeconomic gradients (adjusted HR 1.07; 95% CI: 0.76
      to 1.51 for high vs low economic worry; adjusted HR 1.72; 95% CI: 1.23 to 2.42
      for completed university education vs less than high school). Strong increases in
      the relative hazard for time to first injury were identified for longer work
      hours on the farm. CONCLUSIONS: Socioeconomic factors have been cited as
      important risk factors for injury on farms. However, our findings suggest that
      interventions aimed at the prevention of farm injury are better focused on
      operational factors that increase risk, rather than economic factors per se.

PMID- 21729152
TI  - A trial of an all-terrain vehicle safety education video in a community-based
      hunter education program.
AB  - PURPOSE: All-terrain vehicle (ATV) injury is an increasingly serious problem,
      particularly among rural youth. There have been repeated calls for ATV safety
      education, but little study regarding optimal methods or content for such
      education. The purpose of this study was to determine if an ATV safety video was
      effective in increasing ATV safety knowledge when used in a community-based
      statewide hunter education program. METHODS: During the baseline phase, surveys
      focusing on ATV safety were distributed to students in the Arkansas hunter safety
      program in 2006. In the intervention phase a year later, an ATV safety video on
      DVD was provided for use in required hunter education courses across Arkansas.
      The same survey was administered to hunter education students before and after
      the course. FINDINGS: In the baseline phase, 1,641 precourse and 1,374 postcourse
      surveys were returned and analyzed. In the intervention phase, 708 precourse and
      694 postcourse surveys were completed. Student knowledge of ATV safety after
      watching the video was higher than in preintervention classes. Knowledge of
      appropriate helmet usage increased from 95% to 98.8% (P < .0001). Awareness of
      the importance of not carrying a passenger behind the driver increased from 59.5%
      to 91.1% (P < .0001). Awareness of importance of hands-on ATV rider training
      increased from 82.1% to 92.4% (P < .0001). CONCLUSIONS: A brief ATV safety video
      used in a hunter education course increased ATV safety knowledge on most
      measures. A statewide hunter education program appears to be a useful venue for
      ATV safety education.

PMID- 21729153
TI  - Pediatric obesity management in rural clinics in California and the role of
      telehealth in distance education.
AB  - OBJECTIVE: To determine health care provider needs related to pediatric obesity
      management in rural California and to explore strategies to improve care through
      telehealth. METHODS: Cross-sectional survey of health care providers who treated
      children and adolescents at 41 rural clinics with existing telehealth
      connectivity. RESULTS: Most of the 135 respondents were family physicians at
      designated rural health clinics serving low-income families. Respondents had
      practiced in rural areas for an average of 10 years. Most providers rated their
      self-efficacy in managing pediatric obesity as 2 or 3 on a 5-point scale. The
      barriers most frequently reported by health care providers were lack of local
      weight management programs, lack of patient motivation, and lack of family
      involvement in treatment. Providers reported that the resources they would find
      most helpful were readily accessible patient education materials, strategies to
      link patients with community treatment programs and training in brief, focused
      counseling skills. Three-quarters of providers already used telehealth for
      distance learning. Providers reported very high interest in participating in
      continuing education on pediatric obesity delivered by telehealth, specifically
      Internet communication with specialists, web-based education, and interactive
      video case-conferencing. CONCLUSIONS: Rural health care providers face several
      barriers related to pediatric obesity management. Targeted interventions provided
      via telehealth to rural health care providers may enhance the care of obese
      children and adolescents. The results of this study provide directions and
      priorities for the design of appropriate interventions.

PMID- 21729154
TI  - Greek children living in rural areas are heavier but fitter compared to their
      urban counterparts: a comparative, time-series (1997-2008) analysis.
AB  - PURPOSE: To compare 12-year (1997-2008) trends in the distribution of Body Mass
      Index (BMI) status and physical fitness test performances among 8- to 9-year-old
      Greek children living in rural and urban areas. METHODS: Population data derived
      from 11 national school-based health surveys conducted from 1997 to 2008.
      Anthropometric measurements and physical fitness test performances (ie,
      multistage shuttle run, vertical jump, small ball throw, and 30-meter sprint)
      from 725,163 children were analyzed. Distribution between rural and urban areas
      was based on the Hellenic National Statistics Service (HNSS) criteria. FINDINGS:
      Trend analysis showed an increase in the prevalence of obesity in children living
      in urban areas from 7.2% in 1997 to 11.3% in 2008 for girls (P < .001) and from
      8.1% to 12.4% (P < .001) for boys. In rural areas, obesity increased from 7% in
      1997 to 13% in 2008 for girls (P < .001), and from 8.2% to 14.1% (P < .001) for
      boys. The annual rate of obesity increase was 40%-50% higher in children from
      rural areas. Nevertheless, rural children presented better performances in all of
      the physical fitness tests examined. Specifically, mean values of aerobic
      performance decreased from 3.58 +/- 1.9 stages in 1997 to 3.02 +/- 2.1 stages in
      2007 for boys (P < .001), and from 2.97 +/- 1.5 stages to 2.53 +/- 1.7 stages (P
      < .001) for girls in urban areas, whereas in rural areas, the correspondent
      values were not significantly different between 1997 and 2007. CONCLUSIONS:
      Childhood obesity rates are higher in rural compared with urban areas in Greece,
      despite an apparent higher fitness level of children living in rural areas.

PMID- 21729155
TI  - Postpartum depression among rural women from developed and developing countries:
      a systematic review.
AB  - PURPOSE: Postpartum depression (PPD) is a significant public health problem, with
      significant consequences for the mother, infant, and family. Available research
      has not adequately examined the potential impact of sociodemographic
      characteristics, such as place of residence, on risk for PPD. Therefore, this
      systematic review and meta-analysis examines the prevalence of and risk factors
      for PPD in rural communities within developed and developing countries, and where
      possible, compares rates to those among urban women. METHODS: Five databases were
      searched, from start dates through early May 2010, using key words relevant to
      PPD and rural residence. Peer-reviewed articles were eligible if a standardized
      assessment of depression was administered to rural mothers within the first year
      postpartum. Data on PPD were extracted from 19 articles, of which 17 provided
      data for meta-analyses. FINDINGS: The overall prevalence of PPD among rural women
      was 27.0% (95% CI, 18.8%-37.2%). Prevalence was somewhat higher among women in
      developing countries (31.3%; 95% CI, 21.3%-43.5%) than among women in developed
      countries (21.5%; 95% CI, 10.9%-38.0%), although there was significant
      heterogeneity among both groups of studies. Comparisons between rural and urban
      women yielded conflicting results. Although established PPD risk factors were
      associated with depression in rural women, additional risk factors were reported
      for rural women from developing countries, such as having 2 or more young
      children. CONCLUSIONS: Longitudinal studies with clearly defined "rural" and
      "comparison" groups are needed to determine whether rural residence is associated
      with increased risk for PPD. The results can inform prevention and treatment
      programs tailored to serve rural women.

PMID- 21729156
TI  - The health of caregiving grandmothers: a rural-urban comparison.
AB  - PURPOSE: The purpose of this study was to compare the characteristics of rural
      versus urban caregiving grandmothers along with their physical and mental health
      status. METHODS: A secondary analysis of data produced from the first wave of a
      longitudinal study of 485 Ohio grandmothers was conducted. Health status was
      measured using the SF-36 Health Survey and the 20-item CES-D depression scale.
      Rural-urban classification was made using Rural Urban Commuting Area (RUCA) codes
      based on resident ZIP codes, identifying 97 rural and 388 urban grandmothers in
      the sample. FINDINGS: The rural and urban grandmothers were similar in age,
      educational level and employment status; however, 90% of the rural grandmothers
      compared with 60% of the urban grandmothers were white. Rural grandmothers were
      most likely to have traditional nonresidential relationships with their
      grandchildren. Approximately 38% of both the rural and urban grandmothers served
      as primary caregivers for their grandchildren, but a lower percentage of rural
      grandmothers lived in multigenerational homes. There was no significant
      difference between the rural and urban grandmothers in relation to physical or
      mental health. Among rural grandmothers, primary caregivers had significantly
      lower levels of mental health compared with the other caregiver groups.
      CONCLUSIONS: These findings suggest that rural and urban grandmothers have
      similar levels of physical and mental health, despite differences in demographics
      and caregiving arrangements. Health promotion efforts with rural caregiving
      grandparents are indicated, addressing both mental and physical health.

PMID- 21729157
TI  - A "medical mission" at home: the needs of rural America in terms of
      otolaryngology care.
AB  - OBJECTIVES: Describe the population, Medicaid, uninsured, and otolaryngology
      practice demographics for 7 representative rural Southeastern states, and propose
      academic-affiliated outreach clinics as a service to help meet the specialty care
      needs of an underserved rural population, based on the "medical mission" model
      employed in international outreach clinics. METHODS: A needs assessment was
      conducted via review of medical licensing and practice location data from state
      medical licensing authorities, together with population, Medicaid, and uninsured
      data from state health/human services departments and the US Census Bureau.
      RESULTS: In all states examined, there are significantly more practicing
      otolaryngologists per capita in urban areas compared to rural areas (P < .05),
      with the exception of West Virginia, where the difference was not statistically
      significant (P= .33). In the majority of the states examined, there were higher
      rates (expressed as a percentage of total county population) of both Medicaid
      recipients and uninsured patients in rural counties compared to urban counties.
      Notable exceptions include Louisiana and West Virginia, where there are higher
      percentages of Medicaid patients in urban areas, and Kentucky and Tennessee,
      where there are higher percentages of uninsured patients in the urban areas (P <
      .05 for each comparison). CONCLUSIONS: Borrowing design elements from the
      international outreach clinics, which involve many US otolaryngologists, a
      similar medical mission model could be of benefit domestically. There are rural
      areas of the Southeast where visiting outreach clinics could improve access to
      otolaryngology care and facilitate effective use of existing "safety net" health
      care resources.

PMID- 21729158
TI  - Cancer screening practices among Amish and non-Amish adults living in Ohio
      Appalachia.
AB  - PURPOSE: The Amish, a unique community living in Ohio Appalachia, have lower
      cancer incidence rates than non-Amish living in Ohio Appalachia. The purpose of
      this study was to examine cancer screening rates among Amish compared to non
      Amish adults living in Ohio Appalachia and a national sample of adults of the
      same race and ethnicity in an effort to explain cancer patterns. METHODS: Face-to
      face interviews focusing on perception of risk, cancer screening behaviors, and
      screening barriers were conducted among Amish (n = 134) and non-Amish (n = 154)
      adults living in Ohio Appalachia. Cancer screening rates were calculated and then
      compared to a national sample of adults. FINDINGS: More Ohio Appalachia non-Amish
      males (35.9% vs 14.5%; P= .022) and females (33.3% vs 12.5%; P= .008) reported
      that they would probably develop cancer in the future compared to Amish males and
      females. Amish adults had significantly lower prostate (13.5% vs 63.1% vs 44.6%;
      P < .001), colorectal (males: 10.3% vs 40.0% vs 37.2%, females: 8.6% vs 31.6% vs
      42.9%; P < .001), cervical (48.0% vs 84.0% vs 80.0%; P < .001), and female breast
      (24.8% vs 53.7% vs 56.9%; P < .05) cancer screening rates compared to Ohio
      Appalachia non-Amish participants and a national sample of adults, respectively.
      Barriers to cancer screening were similar among the 2 Ohio groups; however, Amish
      males reported that prostate cancer screening was not necessary more often than
      did Ohio Appalachia non-Amish males (78.6% vs 16.7%; P= .003). CONCLUSIONS: Lower
      rates of cancer screening were documented among the Amish and may be a
      contributing factor to the reduced cancer incidence rates reported among this
      population.

PMID- 21729159
TI  - Talking about, knowing about HIV/AIDS in Canada: a rural-urban comparison.
AB  - PURPOSE: To explore information exchange about HIV/AIDS among people living in
      rural and urban communities and to assess the value of social capital theory, as
      well as demographic factors, in predicting community members' knowledge of
      HIV/AIDS and their likelihood of having talked about the disease. METHOD: A
      random-digit dial telephone survey was conducted in 3 rural regions and matched
      urban communities in Canada during 2006 and 2007. A total of 1,919 respondents
      (response rate: 22.2%) answered questions about their knowledge of and attitudes
      toward HIV/AIDS, their social networks, whether they were personally acquainted
      with a person with HIV/AIDS (PHA), and whether they had ever talked to anyone
      about HIV/AIDS. FINDINGS: Rurality was a significant predictor of HIV/AIDS
      knowledge and discussion. Even after controlling for factors such as age and
      level of education, respondents living in rural regions were less knowledgeable
      about HIV/AIDS and were less likely to have spoken with others about the disease.
      Social capital theory was not as strongly predictive as expected, although people
      with more bridging ties in their social networks were more likely to have
      discussed the disease, as were those who knew a PHA personally. CONCLUSION: Rural
      dwelling Canadians are less likely than their urban counterparts to be
      knowledgeable about HIV/AIDS or to talk about it, confirming reports by PHAs that
      rural communities tend to be silent about the disease. The findings support
      policy recommendations for HIV education programs in rural areas that encourage
      discussion about the disease and personal contact with PHAs.

PMID- 21729160
TI  - Primary care clinicians' perspectives on management of skin and soft tissue
      infections: an Iowa Research Network study.
AB  - An estimated 95,000 people developed methicillin-resistant Staphylococcus aureus
      (MRSA) infections during 2005 of which 14% were community-associated and 85% were
      hospital or other health setting associated, and 19,000 Americans died from these
      infections that year. PURPOSE: To explore health care providers' perspectives on
      management of skin and soft tissue infections to gain a better understanding of
      the problems faced by busy providers in primary care settings. METHODS: Focus
      group meetings were held at 9 family physician offices in the Iowa Research
      Network. Seventy-eight clinicians including physicians, nurses, nurse
      practitioners, and house officers attended. Meeting audiotapes were transcribed
      and coded by 3 investigators, and a MRSA-management taxonomy was developed.
      FINDINGS: The main themes that emerged from the focus groups included
      epidemiology, diagnosis, treatment, management, prevention, special populations,
      and public relations. The incidence of MRSA infections was perceived to have
      increased over the past decade. However, diagnosis and treatment protocols for
      physicians in the outpatient setting have lagged behind, and no well-accepted
      diagnostic or treatment algorithms were used by physicians attending the focus
      groups. CONCLUSION: The clinicians in this study noted considerable confusion and
      inconsistency in the management of skin and soft tissue infections, particularly
      those due to MRSA.

PMID- 21729161
TI  - Meaningful use of health information technology by rural hospitals.
AB  - PURPOSE: This study examines the current status of meaningful use of health
      information technology (IT) in Critical Access Hospitals (CAHs), other rural, and
      urban US hospitals, and it discusses the potential role of Medicare payment
      incentives and disincentives in encouraging CAHs and other rural hospitals to
      achieve meaningful use. METHODS: Data from the American Hospital Association
      (AHA) Annual Survey IT Supplement were analyzed, using t tests and probit
      regressions to assess whether implementation rates in CAHs and other rural
      hospitals are significantly different from rates in urban hospitals. FINDINGS: Of
      the many measures we examined, only 4 have been met by a majority of rural
      hospitals: electronic recording of patient demographics and electronic access to
      lab reports, radiology reports, and radiology images. Meaningful use is even less
      prevalent among CAHs. We also find that rural hospitals lag behind urban
      institutions in nearly every measure of meaningful use. These differences are
      particularly large and significant for CAHs. CONCLUSION: The meaningful use
      incentive system creates many challenges for CAHs. First, investments are
      evaluated and subsidies determined after adoption. Thus, CAHs must accept
      financial risk when adopting health IT; this may be particularly important for
      large expenditures. Second, the subsidies may be low for relatively small
      expenditures. Third, since the subsidies are based on observable costs, CAHs will
      receive no support for their intangible costs (eg, workflow disruption). A
      variety of policies may be used to address these problems of financial risk,
      uncertain returns in a rural setting, and limited resources.

PMID- 21729163
TI  - Chronic actinic dermatitis in Asian skin: a Singaporean experience.
AB  - BACKGROUND/PURPOSE: To study the characteristics of chronic actinic dermatitis
      (CAD) in a heterogeneous group of Singaporean patients. METHODS: The
      photobiologicial features of all patients phototested and diagnosed with CAD from
      January 2005 to December 2009 were examined retrospectively. RESULTS: Fifty-eight
      patients were diagnosed as having CAD. The mean age at diagnosis was 62 years
      (range 35-83). Forty-one were (70.7%) Chinese, six (10.3%) Indians, eight (13.8%)
      Malays, and three (5.2%) Others. Forty-seven were (81.0%) male and 11 (19.0%)
      were female. Forty-nine (84.5%) had Fitzpatrick skin phototype IV and nine
      (15.5%) had phototype V. Three of 26 (11.5%) tested for human immunodeficiency
      virus were positive. The face, neck, and forearms were most commonly affected.
      Thirty-two patients (55.2%) had reduced minimal erythema dose (MED) to both
      ultraviolet B (UVB)and ultraviolet A (UVA), 23 patients (39.7%) had lowered MED
      to UVB only, while three (5.1%) had reduced MED to UVA only. Patients were
      followed up for a mean of 16.8 months. All were treated with photoprotection and
      topical steroids; however, a few required oral immunosuppression with partial
      improvement. CONCLUSION: In Singapore, CAD was seen more commonly in elderly
      Chinese males of Fitzpatrick skin phototype IV. Reduced MED to both UVB and UVA
      was the most common phototest finding.

PMID- 21729164
TI  - A randomized clinical comparative study of cryotherapy plus photodynamic therapy
      vs. cryotherapy in the treatment of multiple condylomata acuminata.
AB  - BACKGROUND: Cryotherapy cannot destroy subclinical human papillomavirus-infected
      cells of condylomata acuminata (CA). The topical application of aminolevulinic
      acid (ALA) results in a shallow penetration depth in CA lesions (1). OBJECTIVES:
      To compare the efficacy and safety of cryotherapy plus ALA-photodynamic therapy
      (PDT) with cryotherapy in the treatment of multiple CA. METHODS: Eighty patients
      with multiple CA received cryotherapy plus ALA-PDT (n=40) or cryotherapy plus
      placebo-PDT (n=40). After cryotherapy, a 20% ALA or a placebo solution was
      applied to the CA area 3 h before illumination with red light (635 nm, 100
      mW/cm(2) , 100 J/cm2). The treatment was repeated 7 days after the first
      treatment if the lesions were not completely resolved. The complete response
      rate, recurrence rate and adverse effects in the two groups were analyzed.
      RESULTS: After two treatments, the complete response rates in the combined group
      (cryotherapy plus ALA-PDT) and cryotherapy group were 32.4% (36/111) and 32.6%
      (43/132) in the anal area (P>0.05), 100% (32/32) and 54.5% (18/33) in the
      urethral meatus (P<0.05), and 94.2% (129/137) and 50.5% (56/111) in the external
      genitals (P<0.05), respectively. The recurrence rates in the combined group and
      cryotherapy group were 24.3% (27/111) and 31.1% (41/132) in the anal area
      (P>0.05), 9.4% (3/32) and 39.4% (13/33) in the urethral meatus (P<0.05), and 3.6%
      (5/137) and 31.5% (35/111) in the external genitals (P<0.05), respectively. The
      adverse effects in each group included mild to moderate pain, edema, erosion and
      hypopigmentation, without any infection, ulcers, scarring or urethral
      malformations. CONCLUSION: Cryotherapy plus ALA-PDT is a more effective regimen
      for the treatment of multiple CA compared with cryotherapy alone.

PMID- 21729165
TI  - The impact of different fluence rates on pain and clinical outcome in patients
      with actinic keratoses treated with photodynamic therapy.
AB  - BACKGROUND/PURPOSE: Literature data suggest that lower fluence rates are
      preferable in terms of clinical response and tolerability for treating patients
      with actinic keratoses (AKs). We aimed to clarify the impact of different fluence
      rates on pain during photodynamic therapy (PDT) for AKs, as well as on treatment
      outcome. METHODS: Individuals with at least three discrete AKs were recruited.
      Each lesion was randomly allocated to 25, 50 or 75 mW/cm2 of topical 5
      aminolevulinic acid (5-ALA) PDT, using non-coherent light source. Primary end
      point was pain during illumination, evaluated using a visual analogue scale
      (VAS). Secondary end points were clinical outcome and adverse events. RESULTS:
      Fifty adults, with 150 AKs lesions were recruited in the study. Mean VAS score
      did not significantly differ between the groups of 25 and 50 mW/cm2 (P=0.714).
      However, mean VAS was significantly higher at the group of 75 mW/cm2 in
      comparison to the former ones (P=0.000). With respect to the clinical outcome and
      adverse events during the first year of follow-up, no differences were observed
      between the three groups. Comparison between the 25 and the 50 mW/cm2 (P=0.749),
      as well as between the former and the 75 mW/cm2, did not show a dependence of
      complete response rate on fluence (P=0.749 and P=1.000, respectively).
      CONCLUSIONS: According to our observations a fluence rate between 25 and 50
      mW/cm2 is effective and better tolerated by patients treated with topical 5-ALA
      PDT for AKs.

PMID- 21729166
TI  - 311 nm ultraviolet B-accelerated response of psoriatic lesions in adalimumab
      treated patients.
AB  - BACKGROUND: Treatment with the tumor necrosis factor-alpha antibody adalimumab
      for 12-16 weeks produces a satisfactory response [i.e., 75% reduction in
      psoriasis area and severity index (PASI)] in a majority (70-80%) of patients with
      psoriasis. We asked whether 311 nm ultraviolet B (UVB) can improve therapeutic
      response of psoriatic lesions to adalimumab. METHODS: Four patients (age range,
      49-67 years) with moderate to severe plaque-type psoriasis were treated with
      standard dosage of adalimumab. During adalimumab therapy, a randomly selected
      body half (left or right, excluding the head) was irradiated with 311 nm UVB
      three times weekly for 6 weeks. Treatment response was monitored weekly in terms
      of half-body PASI. RESULTS: 311 nm UVB significantly accelerated the therapeutic
      response during adalimumab treatment. At the start of 311 nm UVB therapy, the
      mean PASI was 14.8. After 6 weeks of 311 nm UVB therapy, the mean PASI was 2.0 on
      UV-irradiated body halves and 6.9 on non-irradiated body halves (difference, 4.9;
      95% confidence interval, 0.4-9.4; P=0.041; 2-tailed paired t-test). This
      corresponded to an overall mean PASI reduction from baseline (i.e., adalimumab
      start) of 86% on UV-irradiated body halves vs. 53% on non-irradiated body halves.
      CONCLUSION: 311 nm UVB may accelerate and improve the clearance of psoriatic
      lesions in adalimumab-treated patients.

PMID- 21729167
TI  - Differences in sun exposure habits between self-reported skin type and
      ultraviolet sensitivity measured by phototest.
AB  - BACKGROUND: Traditionally, classification of skin reactivity to ultraviolet (UV)
      light is based on self-estimation of tendency to burn and tan (Fitzpatrick's
      classification). Although widely accepted, the model has shown to correlate
      poorly with actual UV sensitivity, measured by phototest. The aim of the present
      study was to investigate how self-estimated skin type, according to Fitzpatrick,
      and actual UV sensitivity measured by phototest correlate with sun exposure and
      protection. METHODS: One hundred and sixty-six voluntary patients visiting their
      general practitioner for investigation of suspicious skin tumours were recruited
      for the study, and filled out a questionnaire, mapping sun habits and sun
      protection behaviour, based on five-point Likert responses. The patients reported
      their skin type (I-VI) according to Fitzpatrick, and a phototest was performed to
      determine the minimal erythema dose. RESULTS: For most of the questions, high
      self-estimated UV sensitivity, according to Fitzpatrick, appeared to be
      associated with a higher level of sun avoidance/protection (P<0.05). For actual
      UV sensitivity, however, the difference in response distribution was only
      significant for sunscreen use, and did not show a similar apparent association
      related to the degree of UV sensitivity. CONCLUSION: Self-estimated skin UV
      sensitivity, according to Fitzpatrick's classification, appears to be a stronger
      predictor of sun exposure and protection than actual UV sensitivity measured by
      phototest.

PMID- 21729168
TI  - Parental perspective on sun protection for young children in Bavaria.
AB  - BACKGROUND: Exposure to ultraviolet (UV) radiation is the most important
      modifiable risk factor for skin cancer. Parents are responsible for sun
      protection of their young children and thus their knowledge and attitudes should
      be assessed. METHODS: A survey that included 2619 children aged 3-6 years
      (response: 64.7%) was performed in Erlangen during 2001/2002. Parents' attitude,
      knowledge and behavior regarding sun protection were ascertained by using a self
      administered questionnaire. Demographic and photosensitivity data of the children
      were recorded, along with the UV radiation-related outcomes. RESULTS: Most
      parents correctly recognized the risk factors of skin cancer, except the
      intermittent and intensive sun exposure. Nevertheless, most parents also agreed
      with statements regarding sun- and tanning related beauty and well-being. The
      overwhelming majority of parents stressed the necessity of sun protection for
      their children; however, 50% of the children experienced some form of solar
      radiation injury during the preceding summer. Children eagerly pursued outdoor
      activities, especially boys compared with girls (P<0.01). A gender difference was
      also apparent, with boys showing more willingness to wear hats than girls
      (P<0.01). CONCLUSION: The relatively high level of knowledge was in contrast to a
      prevalent attitude of regarding sunlight as enhancing health and well-being. This
      may hamper UV radiation avoidance strategies. Thus, future campaigns should not
      only address preventive knowledge but also focus on associated attitudes to
      effectively modify the behavior.

PMID- 21729169
TI  - Ginsenoside Rb1, Rg1 and three extracts of traditional Chinese medicine attenuate
      ultraviolet B-induced G1 growth arrest in HaCaT cells and dermal fibroblasts
      involve down-regulating the expression of p16, p21 and p53.
AB  - OBJECTIVE: The aims of this study were to confirm whether traditional Chinese
      medicine ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1), polygonum multiflorum
      (PM), ginkgo extract (GE) and lycium barbarum polysaccharide (LBP) can attenuate
      G1 growth arrest of HaCaT cells and dermal fibroblasts induced by 10 subcytotoxic
      ultraviolet B (UVB) exposures, and to explore the possible mechanism in terms of
      the expression of cell-cycle regulatory proteins p16, p21 and p53. METHODS: Ten
      subcytotoxic exposures to UVB induced G1 growth arrest of HaCaT cells and dermal
      fibroblasts. Cell-cycle analysis was performed using flow cytometry, and mRNA
      levels of p16, p21 and p53 were detected by a reverse transcription-polymerase
      chain reaction (RT-PCR), and protein levels were detected using Western blot
      analysis. RESULTS: Five types of traditional Chinese medicine attenuated UVB
      induced G1 growth arrest. The mRNA and protein levels of p16, p21 and p53 in
      HaCaT cells and dermal fibroblasts increased after UVB irradiation, but
      pretreatment with five types of traditional Chinese medicine decreased the
      expression of p16, p21 and p53. CONCLUSIONS: These results indicated that five
      types of traditional Chinese medicine can attenuate G1 growth arrest of HaCaT
      cells and dermal fibroblasts induced by UVB exposures, which was caused by down
      regulating the expression of cell-cycle regulatory proteins p16, p21 and p53.

PMID- 21729170
TI  - Persistent photodamage following drug photosensitization in a lung-transplant
      recipient.
AB  - Photosensitivity is a well-known complication of treatment with quinolone
      antibiotics. Several transient phototoxic drug reactions have been described. We
      report a case of a persistent phototoxic reaction to ciprofloxacin in a lung
      transplant recipient on a long-term immunosuppressive drug regimen.

PMID- 21729171
TI  - Successful treatment of generalized childhood Schamberg's disease with narrowband
      ultraviolet B therapy.
AB  - Pigmented purpuric dermatoses are a group of dermatoses characterized by petechia
      and hyperpigmented macules that occur predominantly on the lower extremities.
      Although it is most commonly seen in adults, this disease can also affect
      children. Phototherapy has been shown to be effective in some cases in the
      literature. Here, we present two cases of Schamberg's disease that improved
      rapidly with narrowband ultraviolet B (UVB) therapy. To our knowledge, they were
      the first pediatric cases of successful narrowband UVB therapy in this disease.

PMID- 21729172
TI  - Erythema multiforme photoinduced by paroxetine and herpes simplex virus.
AB  - Erythema multiforme (EM) is a self-limited skin disease, characterized by the
      abrupt onset of symmetric red papules that may evolve into target lesions often
      precipitated by an infection. Photosensitive erythema multiforme (PEM) is a rare
      disorder characterized by the distribution of the lesions on sun-exposed areas.
      It has been described at the sites of sunburn, following episodes of polymorphic
      light eruption or herpes labialis and in association with drugs. To our
      knowledge, PEM photoinduced by selective serotonin reuptake inhibitors has not
      been reported. We describe a patient who had two consecutive episodes of PEM
      related to two different triggers: paroxetine and HSV infection. In the first
      episode, systemic photosensitivity was confirmed with the photobiological study.
      UVB-MED was decreased when the patient was taking paroxetine and did not change
      after its substitution for duloxetine. However, it became normal after the
      withdrawal of both drugs, suggesting a cross-reactivity reaction. The UVB
      photopatch test with paroxetine was positive. The second episode occurred after a
      herpes labialis relapse. At that time, UVB-MED was normal.

PMID- 21729173
TI  - Photodistributed eruption with rhabdomyolisis due to leflunomide.

PMID- 21729174
TI  - Experimental testing of skin reactions to insulin detemir in diabetes patients
      naive to insulin detemir.
AB  - BACKGROUND/AIMS: Sporadic reports on immediate and delayed cutaneous reactions to
      insulin detemir, a modern insulin analogue, have raised unsupported claims of
      allergy of type I, III and IV. The purpose of this experimental study using a
      provocative design was to elucidate the potential mechanisms behind such skin
      reactions. MATERIAL AND METHODS: A total of 40 patients with type 1 diabetes or
      insulin-requiring type 2 diabetes, all naive to insulin detemir, were injected on
      the thigh with 0.l mL of insulin detemir (Levemir((r))) administered with an 8 mm
      needle at three different depths, i.e. intradermal, subdermal and subcutaneously.
      Saline was injected as control. Any cutaneous reactions were assessed after 10
      and 30 min, after 24 and 48 h and after 7 days. Histopathology of positive
      reactions on day 7 was obtained. The study was randomized, controlled, double
      blinded, and conducted in accordance with ICH-GCP guidelines. Blood flow was
      recorded with the Periflux PF5010, and skin colour (a*) with the DSMII
      colorimeter. RESULTS: Clinical reading, flowmetry and colorimetry consistently
      showed delayed reactions after intradermal insulin injection (35 of 40 patients
      reacted with mainly weak reactions, P<0.05), peaking after 48 h, contrasting no
      special reaction immediately after injection, except for reactions attributed to
      needle trauma. A total of 22 patients reacted on subdermal injection and 21 on
      subcutaneous injection. Histopathology on day 7 from 22 reactions in 15 patients
      showed a consistent pattern of inflammation with eosinophilia as typically
      observed in adverse skin reactions to a variety of medicines. Reactions were
      interpreted as non-specific biologic responses to the insulin different from
      direct toxic actions and classical allergic reaction patterns. Only one person
      registered itch/discomfort. A prick test vs. histamine reference excluded insulin
      detemir to be a pharmacological histamine releaser. Thus, provocative testing
      with insulin detemir produced delayed skin reaction but no immediate reaction.
      Measurement of circulating insulin detemir-specific antibodies by RIA before and
      after 3 months showed no increase. CONCLUSION: Non-allergic delayed skin
      reactions from intradermal and, to a minor degree, subdermal and subcutaneous
      injections of insulin detemir were frequent in this experimental study and showed
      a consistent histology pattern of inflammation with eosinophilia. Immediate
      reactions were not produced. The reactions are unlikely to be specific for
      insulin detemir, and other insulins should be studied in a similar provocative
      design.

PMID- 21729175
TI  - Meningitis caused by Filobasidium uniguttulatum: case report and overview of the
      literature.
AB  - Cryptococcal meningitis is mainly caused by Cryptococcus neoformans and
      Cryptococcus gattii, but occasionally other Cryptococcus species and
      phylogenetically related species are involved. Herein, we present a case of
      cryptococcal meningitis from China, which was caused by an azole and flucytosine
      resistant Filobasidium uniguttulatum. In addition, we present an overview of the
      literature of meningitis caused by Cryptococcus species other than C. neoformans
      and C. gattii. Eight cases were related to infections of the central nervous
      system. Leukaemia and cancer were important risk factors in HIV-negative
      patients. Molecular identification and susceptibility testing are important for
      proper management of patients because the species involved may differ in
      susceptibility to antifungal drugs.

PMID- 21729176
TI  - The effect of two different routes of administration of oxytocin on peripheral
      plasma prostaglandin F(2alpha) metabolite levels in early post-partum dairy cows.
AB  - Various parenteral treatment forms of oxytocin, as often used under praxis
      circumstances, may act differently on contractility of the uterus during the
      first days of the puerperium. Various patterns of such induced uterotonic
      responses may lead to alterations in the emptying characteristics of the uterine
      lumen, thus influencing, as a late consequence, the process of involution.
      Therefore, this study was designed to test whether two different parenteral
      administration forms of oxytocin induce changes in peripheral plasma
      concentrations of 15-ketodihydro-prostaglandin F(2alpha) (PGF(2alpha) metabolite)
      in early post-partum cows. Between 13 and 15 h after uncomplicated calving,
      healthy dairy cows without retained foetal membranes were treated with 50 IU
      oxytocin, either intramuscularly (OT-IM group; n = 15) or intravenously (OT-IV
      group; n = 16). Saline solution was administered intramuscularly as controls (CON
      group; n = 15). Jugular blood samples were taken at 10-min intervals from 1 h
      before to 2 h after treatment. Plasma PGF(2alpha) metabolite levels were measured
      by radioimmunoassay. No significant differences in peripheral plasma PGF(2alpha)
      metabolite concentrations occurred in the OT-IM and CON groups, but mean values
      significantly increased in the OT-IV group, peaking at 20 min after treatment and
      reaching pre-treatment baseline values again at 120 min. Although the source of
      prostaglandins was not investigated in this study, our results suggest that
      exogenous oxytocin may enhance secretion of prostaglandins by the uterus during
      the first day after normal calving. These prostaglandins might contribute, by an
      endocrine or paracrine route, to the stimulation of myometrial contractility when
      exogenous oxytocin is given during this early post-partum stage.

PMID- 21729177
TI  - Effects of GnRH or progesterone treatment on day 5 post-AI on plasma
      progesterone, luteal blood flow and leucocyte counts during the luteal phase in
      dairy cows.
AB  - This study was designed to test the effects of progesterone or GnRH treatment on
      day 5 post-AI on fertility and luteal function in dairy cows and heifers. Five
      days after AI, 32 animals were randomly assigned to a control, intravaginal
      progesterone for 14 days progesterone releasing intravaginal device (PRID) or
      GnRH treatment group. On days 5, 7, 12, 14, 17 and 19 post-AI, each animal
      underwent colour Doppler ultrasonography of the corpus luteum and blood samples
      were collected for cell counts and plasma progesterone determination. Through
      general linear model repeated measures analysis of variance, significant effects
      were observed of treatment, parity, inseminating bull, reduced vascularization of
      the CL and pregnancy on plasma progesterone concentrations, whereas mean plasma
      progesterone and time luteal phase day, and treatment and plasma progesterone
      concentration on day 5 post-AI were found to, respectively, affect neutrophil and
      lymphocyte counts throughout the luteal phase. Moreover, two binary logistic
      regression analyses were performed. Based on the odds ratio, the likelihood of
      pregnancy by days 26-32 post-AI was 23.4 times higher in animals with high mean
      progesterone levels throughout the study period, compared with animals with low
      mean progesterone. The likelihood of reduced CL vascularization was 14 times
      higher in animals treated with PRID, compared with control and GnRH-treated
      animals. In conclusion, our results indicate that treatment on day 5 post-AI with
      PRID reduced subsequent CL vascularization, whereas GnRH treatment increased
      plasma progesterone concentrations on day 12 post-AI, although an effect was
      identified of the inseminating bull on plasma progesterone levels. Pregnant
      animals showed higher mean plasma progesterone concentrations than in nonpregnant
      ones and heifers higher than in lactating cows, whereas blood cell counts
      differed depending on the treatment and on the mean plasma progesterone
      concentration on day 5 post-AI.

PMID- 21729178
TI  - Acute changes in the concentrations of prostaglandin F2alpha (PGF) and cortisol
      in uterine and ovarian venous blood during PGF-induced luteolysis in cows.
AB  - Prostaglandin F2alpha (PGF) is considered to be the main luteolysin in cattle. We
      have previously demonstrated that cortisol (Cr) suppresses PGF production in non
      pregnant bovine endometrium. This study was carried out to test whether exogenous
      PGF increases ovarian and/or uterine PGF production and to determine the temporal
      relationship between PGF and Cr in ovarian and uterine circulations during PGF
      induced luteolysis in cows. Catheters were inserted into the ovarian vein (OV),
      uterine vein (UV) and jugular vein (JV) of 10 cows on Day 9 of the oestrous cycle
      (Ovulation = Day 0) for frequent blood collection. On Day 10, the cows were
      divided randomly into two groups and treated with a luteolytic dose of a PGF
      analogue (cloprostenol) or saline solution. Blood samples were collected at 
      0.25, 0, 0.25, 0.5, 1 and 2 h and then at 2-h intervals until 12 h after
      treatment (0 h). The basal concentrations of PGF and Cr in OV and UV plasma were
      not significantly different. Injection of a PGF analogue induced more than
      twofold increases in the levels of PGF between 0.25 and 1 h in UV plasma, but not
      in OV plasma. PGF increased (p < 0.05) the concentrations of Cr in OV, UV and JV
      plasma between 0.5 and 1 h. The Cr levels in OV, UV and JV plasma were similar.
      The PGF levels in UV plasma decreased after Cr reached its highest levels. The
      overall results suggest that the uterus rather than the ovary increases PGF
      production in response to PGF injection. Based on the temporal changes of PGF and
      Cr in the ovarian and uterine circulations, Cr may act to reduce uterine PGF
      production in non-pregnant cows in vivo.

PMID- 21729179
TI  - Effect modification of immunoglobulin E-mediated atopy and rhinitis by
      glutathione S-transferase genotypes in passive smokers.
AB  - BACKGROUND: Experimental studies suggest that glutathione S-transferase (GST)
      genotypes modify nasal allergen responses induced by secondhand smoke (SHS)
      exposure. OBJECTIVE: We aimed to investigate whether GSTs affected systemic IgE
      and allergic rhinitis (AR) in SHS-exposed individuals from a population-based
      cohort. METHODS: Analyses comprised 2309 never-smokers from the Swiss study on
      air pollution and health in adults cohort, reporting SHS status at baseline and
      11 years later. Outcomes were defined by total serum IgE>=100 kU/L, specific
      serum IgE determined by Phadiatop(r) >=0.35 kU/L and self-reported AR. GSTP1
      Ile105Val, GSTM1 and GSTT1 gene deletion genotypes were identified at the follow
      up survey. RESULTS: After adjustment for relevant covariates, the homozygous
      GSTP1 105-Val genotype was negatively associated with high total IgE and high
      specific IgE by Phadiatop(r), notably in subjects persistently exposed to SHS
      (OR: 0.20, 95% CI 0.05-0.75; P=0.02, for high total IgE and OR: 0.29, 95% CI 0.10
      0.89; P=0.03, for high specific IgE by Phadiatop(r)). Carrying at least one copy
      of the GSTM1 gene (non-null) showed a similar association for high specific IgE
      by Phadiatop(r) (OR: 0.41, 95% CI 0.22-0.76; P=0.004). No significant
      associations were found between GSTs and rhinitis. CONCLUSION AND CLINICAL
      RELEVANCE: In this large cohort, homozygosity for GSTP1 105-Val or carrying the
      GSTM1 non-null genotype decreased the risk of high total IgE or high specific IgE
      using Phadiatop(r) by nearly half in subjects exposed to SHS, as compared with
      subjects carrying opposite alleles. These findings underline the value of genetic
      susceptibility when evaluating the effects of environmental exposure on allergic
      illness. The potential long-term effects of persistent SHS exposure in
      genetically vulnerable individuals may be of public health relevance.

PMID- 21729180
TI  - Effects of furosemide on allergic asthmatic responses in mice.
AB  - BACKGROUND: The syndrome of allergic asthma features reversible
      bronchoconstriction, airway inflammation and hyperresponsiveness as well as
      airway remodelling, including goblet cell hyperplasia. Managing severe asthma is
      still a clinical challenge. Numerous studies report that furosemide, an inhibitor
      of Na(+)-K(+)-Cl(-) cotransporter (NKCC) reduces airway hyperresponsiveness (AHR)
      in asthmatic patients. However, the mechanism by which furosemide exerts anti
      asthmatic action remains unclear. OBJECTIVE: This study sought to investigate the
      cellular profile of NKCC1 expression in the lung and examine the effects of
      furosemide on several outcome measurements in a mouse model of allergic asthma.
      METHODS: Mice were sensitized and challenged with ovalbumin (OVA). Before
      challenge, the OVA-sensitized mice were treated with furosemide (4.0 mg/kg/day,
      via daily intraperitoneal injection for 5 days). Outcome measurements in naive,
      OVA-exposure, furosemide-treated naive and furosemide-treated OVA-exposed mice
      included the slope of the relationship between inhaled methacholine (MCh)
      concentration and respiratory system resistance (Slope.R(RS)), bronchoalveolar
      lavage (BAL) cell counts and immunohistochemical and immunoblotting assays of
      lung tissues. RESULTS: NKCC1 immunoreactivity was observed in airway epithelial
      cells (AECs) and alveolar type II (ATII) cells of the control mice. OVA exposure
      enhanced the expression of NKCC1 in AECs and ATII cells, and increased the
      infiltration of NKCC1-expressing T lymphocytes in the lung. NKCC1
      immunoreactivity was not detected in the airway smooth muscle (ASM) cells.
      Furosemide treatment reduced the Slope.R(RS) in both naive and OVA-exposed mice
      by about 50%. Furosemide treatment also increased T lymphocyte infiltration to
      the lung in OVA-exposed mice by approximately 53%, but had no effect on pulmonary
      goblet cell hyperplasia. CONCLUSIONS AND CLINICAL RELEVANCE: Furosemide decreases
      basal airway responsiveness, thereby reducing the extent of allergen-induced AHR.
      However, the same treatment also increases T lymphocytes infiltration in the
      course of allergic asthma. Further studies are necessary to address the
      usefulness of furosemide in the clinical treatment of asthma.

PMID- 21729181
TI  - Mechanisms of immunotherapy to wasp and bee venom.
AB  - Hymenoptera venoms are important allergens that can elicit both local and
      systemic allergic reactions, including life-threatening anaphylaxis. Venom
      immunotherapy (VIT) remains the most effective treatment, reducing the risk of
      systemic reactions in individuals with Hymenoptera venom allergy. VIT can restore
      normal immunity against venom allergens and provide patients with a lifetime of
      tolerance to venoms. During VIT, peripheral tolerance is induced by the
      generation of allergen-specific regulatory T (Treg) cells, which suppress
      proliferative and cytokine responses against the venom allergens. Treg cells are
      characterized by IL-10 secretion that directly or indirectly influence effector
      cells of allergic inflammation, such as mast cells, basophils and eosinophils.
      Treg cells also have influence on B cells, suppressing IgE production and
      inducing the production of blocking type IgG4 antibodies against venom allergens.
      An accumulating body of evidence suggests that Treg cells may affect allergen
      sensitization and methods for enhancing this cell population may eventually
      improve the efficacy of VIT. In this article, immune mechanisms enrolled in bee
      and wasp VIT are reviewed.

PMID- 21729182
TI  - Effect of inhaled dust mite allergen on regional particle deposition and
      mucociliary clearance in allergic asthmatics.
AB  - BACKGROUND: Acute exacerbations in allergic asthmatics may lead to impaired
      ability to clear mucus from the airways, a key factor in asthma morbidity.
      OBJECTIVE: The purpose of this study was to determine the effect of inhaled house
      dust mite challenge on the regional deposition of inhaled particles and
      mucociliary clearance (MCC) in allergic asthmatics. METHODS: We used gamma
      scintigraphy (inhalation of (99m) Tc -sulphur colloid particles) to measure the
      regional particle deposition and MCC in allergic asthmatics (n=12) 4 h following
      an inhaled dust mite allergen challenge (Dermatophagoides farinae extract;
      PD(max) =fall in forced expiratory volume in 1 s of 10%) for comparison with
      baseline non-challenge measures. RESULTS: In responders (n=9 PD(max) dose), lung
      function returned to pre-challenge values by 3 h but was significantly decreased
      at 6 and 24 h in three of the responders (i.e. late-phase response) and induced
      sputum eosinophils were increased at 24 h post-challenge (P<0.05). Responders
      showed enhanced bronchial airway deposition of inhaled particles (P<0.05) and
      slowed clearance from the central lung zone (P<0.01) at 4 h post-challenge
      compared with the baseline (no allergen challenge) that was predicted by the
      PD(max) allergen concentration (r=-0.70, P<0.05). The decline in lung function at
      24 h post-challenge correlated with reduced MCC from the central lung zone (r=
      0.78, P<0.02) and PD(max) . Non-responders (n=3) showed no change in lung
      function, regional deposition or MCC post-challenge vs. baseline. CONCLUSIONS AND
      CLINICAL RELEVANCE: These data suggest that regional deposition and clearance of
      inhaled particles may be sensitive for detecting mild airway obstruction
      associated with early- and late-phase allergen-induced effects on mucus
      secretions. The study was listed on clinicaltrials.gov (NCT00448851).

PMID- 21729183
TI  - Phenotypic analysis of perennial airborne allergen-specific CD4+ T cells in
      atopic and non-atopic individuals.
AB  - BACKGROUND: Accumulating evidence suggests that T cells play an important role in
      the pathogenesis of atopic dermatitis (AD); yet, little is known of the
      differentiation status of CD4+ T cells specific for common environmental
      allergens, such as the major cat allergen, Fel d 1. OBJECTIVE: To determine the
      frequency, differentiation phenotype and function of circulating Fel d 1-specific
      CD4+ T cells in adult individuals with severe persistent AD in comparison with
      healthy controls. METHODS: Using HLA class II tetrameric complexes based on a HLA
      DPB1*0401-restricted Fel d 1 epitope, ex vivo and cultured T cell frequency and
      phenotype were analysed in individuals with AD and healthy controls. Cytokine
      secretion was measured by ex vivo and cultured IL-4 and IFN-gamma ELISpots.
      RESULTS: Ex vivo Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both
      atopics and non-atopics express high levels of CCR7, CD62L, CD27 and CD28,
      placing the cells largely within the central memory subgroup. However, the
      functional phenotype was distinct, with greater IL-4 production from the cells
      derived from atopics, which correlated with disease severity. CONCLUSIONS AND
      CLINICAL RELEVANCE: Circulating Fel d 1-specific DPB1*0401-restricted CD4+ T
      cells in both atopic and non-atopic donors maintain a central memory phenotype;
      however in atopics, the cells had greater Th2 effector function, compatible with
      a disease model of altered antigen delivery in atopic individuals.

PMID- 21729184
TI  - Visible deposits on a bone marrow aspirate suggested the presence of a metastatic
      carcinoma.

PMID- 21729185
TI  - Nontargeted rapid human immunodeficiency virus screening provided by dedicated
      personnel does not adversely affect emergency department length of stay.
AB  - OBJECTIVES: In September 2006, the Centers for Disease Control and Prevention
      (CDC) recommended routine (nontargeted) human immunodeficiency virus (HIV)
      screening for all patients in the emergency department (ED). Although the
      American College of Emergency Physicians has endorsed these recommendations, the
      College expressed concern that that their adoption may lead to an increase in the
      length of stay (LOS) for ED patients. This study therefore analyzed the effect of
      nontargeted HIV screening on LOS in a cohort of ED patients. METHODS: The
      analysis was performed in an urban, Level I trauma center that offers nontargeted
      opt-out HIV screening using dedicated HIV screeners. The LOS of all discharged
      patients who accepted HIV screening between May 2008 and December 2009 were
      compared with those of a cohort of patients over the same time period who were
      offered an ED HIV screening test but declined or were found to be not eligible.
      Median LOS was compared using the Wilcoxon rank sum test, and a multivariable
      linear model was used to assess the relationship between the acceptance of HIV
      testing and ED LOS. RESULTS: Over the 20-month study period, there were 18,577
      records of discharged patients who were offered an HIV screening test and for
      whom there were data about LOS. Of these, 10,286 patients accepted HIV screening,
      and 8,291 patients declined or were found not to be eligible. Individuals who
      accepted the HIV test had an LOS that was 2% longer compared to those who did not
      accept the test (regression beta coefficient = 1.02, 95% confidence interval [CI]
      = 1.00 to 1.03, p = 0.04). CONCLUSIONS: Human immunodeficiency virus screening
      using an additional staff model has no clinically significant effect on the
      overall LOS for discharged patients.

PMID- 21729187
TI  - Community consultation and public disclosure: preliminary results from a new
      model.
AB  - Emergency medicine research conducted under the exception from informed consent
      (EFIC) regulation enables critical scientific advancements. When EFIC is
      proposed, there is a requirement for broad community consultation and public
      disclosure (CC/PD) regarding the risks and benefits of the study. At the present
      time, no clear guidelines or standards exist for conducting and evaluating the
      CC/PD. This preliminary study tested the feasibility and acceptability of a new
      approach to CC/PD for a large-scale EFIC trial by engaging community members in
      designing and conducting the strategies. The authors enrolled key community
      members (called community advocates for research, or CARs) to use community-based
      participatory methods to design and implement CC/PD. By partnering with community
      members who represent target populations for the research study, this new
      approach has demonstrated a feasible CC/PD plan with greater community
      participation and less cost than previous studies. In a community survey, the
      percentage of community members reporting having heard about the EFIC trial more
      than doubled after employing the new approach. This article discusses initial
      implementation and results.

PMID- 21729188
TI  - Clinical teaching site does not affect test performance in an emergency medicine
      clerkship.
AB  - OBJECTIVES: Increasing the size of medical school classes has resulted in the use
      of community hospitals for emergency medicine (EM) clerkships. While differences
      in clinical experience are expected, it is unclear if they are significant. The
      authors set out to investigate whether or not clinical site affects student
      performance on a standard written exam as a measure of medical knowledge.
      METHODS: This was a retrospective analysis of data from 2005 to 2009 for a
      mandatory fourth-year EM clerkship at one institution that uses academic (EM
      residency), hybrid (residency training site but not EM), and community (no
      residency programs) hospitals as clerkship sites. Multiple variable linear
      regression was used to examine the relationship between clerkship site and end of
      clerkship written exam score. Additional covariates included were the time of
      year the rotation was completed (by 3- or 4-month tertiles) and whether the
      student matched in EM. As test scores increased over the study period, a time
      factor was also included to account for this trend. A p-value of <0.05 was
      required for variable retention in the model. RESULTS: A total of 718 students
      completed the clerkship and had complete data for analysis. Thirty-five students
      matched in EM. A total of 311 rotated at academic sites, 304 at hybrid sites, and
      103 at community sites. After adjusting for covariates, clinical site was not a
      significant predictor of exam score (F(2,691) = 0.42, p = 0.65). Factors
      associated with higher test score were student match in EM (beta coefficient =
      3.4, 95% confidence interval [CI] = 1.0 to 5.7) and rotation in July through
      September (beta coefficient = 1.8, 95% CI = 0.5 to 3.0, against a reference of
      January through April). No significant interaction terms or confounders were
      identified. CONCLUSIONS: This study found no evidence that clerkship site
      affected final exam score. Academic EM clerkships may consider partnering with
      other hospitals for clinical experiences without compromising education.

PMID- 21729189
TI  - Diagnosis of spinal cord compression in nontrauma patients in the emergency
      department.
AB  - OBJECTIVES: The objectives were to evaluate the presenting signs and symptoms of
      spinal cord and cauda equina compression (SCC) and to determine the incidence of
      emergency department (ED) misdiagnosis. METHODS: This was a retrospective chart
      review at an urban, tertiary care hospital of patients discharged from an
      inpatient stay (April 2008 through July 2009) with an International
      Classification of Diseases, Ninth Revision (ICD-9) code indicating spinal
      disease, who had visited the ED for a related complaint within the previous 30
      days, and who had a final diagnosis of new SCC. Trauma and transferred patients
      were excluded. The authors defined a misdiagnosis as no ED-documented diagnosis
      of SCC and failure to perform an appropriate diagnostic study either prior to
      arrival, in the ED, or immediately upon admission. RESULTS: Of 1,231 charts
      reviewed, 63 met inclusion criteria. The most common presenting symptoms in
      patients with SCC were pain (44, 70%), difficulty ambulating (38, 60%), and
      weakness (35, 56%). On physical examination, motor deficits (45, 71%) were more
      common than sensory deficits (27, 43%); however, 15 (24%) patients had no motor
      or sensory deficit, and 13 (23%) patients only had unilateral findings. Impaired
      gait was present in 14 patients of only 20 tested, three of whom had no
      associated motor or sensory deficit. SCC was misdiagnosed in 18 (29%, 95%
      confidence interval [CI] = 19% to 41%) cases, which resulted in a significant
      delay to diagnosis (median = 54 hours, interquartile range [IQR] = 38 to 77 vs.
      5.3 hours, IQR = 3.0 to 15) in these patients. CONCLUSIONS: SCC can have a subtle
      presentation with absent or unilateral motor and sensory deficits, but gait
      ataxia may be an additional finding. ED misdiagnosis of SCC in nontrauma patients
      is common.

PMID- 21729190
TI  - CTA and cocaine-associated chest pain: more evidence is needed.

PMID- 21729192
TI  - Streptococcus pneumoniae serotype 1 causing invasive disease among children in
      Barcelona over a 20-year period (1989-2008).
AB  - Fifty-six isolates of serotype 1 were identified during a 20-year prospective
      study (1989-2008), including all children with culture-proven invasive
      pneumococcal disease (IPD) admitted to a children's hospital in Barcelona. Forty
      eight of them (85.7%) were in children aged >2 years. Complicated pneumonia (n =
      28) and non-complicated pneumonia (n = 20) were the main clinical presentations.
      The frequency of serotype 1 IPD increased from 1999-2003 to 2004-2008: 1.2 to 4.4
      episodes/100 000 children (p <0.001). The ST306 clone were identified in 70.4% of
      isolates. As IPD caused by serotype 1 is mainly detected in older children, a
      vaccination programme for children >2 years should be considered.

PMID- 21729193
TI  - Nosocomial bacteraemia: the most neglected causes of death in Europe?

PMID- 21729194
TI  - Pre-emptive diagnosis and treatment of fungal infections--evaluation of a single
      centre policy.
AB  - Invasive fungal disease (IFD) remains a significant cause of mortality in
      haematology patients. Management strategies range from empiric therapy to pre
      emptive approaches. Prophylaxis with mould-active agents has been evaluated, but
      the optimal strategy remains unclear. We present here a retrospective analysis of
      the pre-emptive strategy implemented at our institution. We analysed 348
      consecutive neutropenic episodes in 234 patients. The main elements of our pre
      emptive strategy included twice-weekly Galactomannan testing and weekly computed
      tomography (CT) scan. Antifungal prophylaxis usually consisted of fluconazole
      (400 mg once weekly). Antifungal treatment was started if criteria for IFD
      (including possible) were fulfilled. Along with the incidence of antifungal
      treatment and IFD, we also analysed the adherence to the strategy. Adherence was
      good but suboptimal with 81% of CT scans having been performed at an interval of
      10 days or less. Concerning antifungal treatment, in 56 episodes the patient was
      receiving a mould-active agent as secondary prophylaxis. Antifungal treatment was
      started during 39% of the remaining episodes. In all, 109 cases of IFD were
      diagnosed, 51 being probable or proven. Forty-nine patients died before day 100,
      IFD directly caused or contributed to death in six patients. Two cases of IFD
      were diagnosed post-mortem and were missed by our pre-emptive strategy. Our pre
      emptive strategy is feasible and safe with an acceptable rate of IFD and
      associated mortality, while avoiding anti-fungal treatment in a significant
      proportion of patients. The exact role of pre-emptive treatment compared with
      systematic mould-active prophylaxis can only be determined in a well-designed
      randomized trial.

PMID- 21729195
TI  - Conditions affecting growth and developmental competence of mammalian oocytes in
      vitro.
AB  - Mammalian ovaries contain a large number of oocytes at different stages of
      growth. To utilize potential female gametes, it is important to develop culture
      systems that permit oocytes to achieve full growth and competence in order to
      undergo maturation, fertilization and development. The desired culture systems
      should meet at least the following three conditions: (i) oocytes remain healthy
      and functional so that they can execute intrinsic programs that direct their
      growth and development; (ii) granulosa cells that are adjacent to oocytes
      proliferate efficiently to prevent oocytes from becoming denuded; and (iii)
      granulosa cells maintain (and develop) appropriate associations with oocytes
      during the culture period. For this reason, several systems have been developed,
      and they can be classified into four categories based on the structure and
      components of the follicle/oocyte-granulosa cell complex and the location of the
      oocyte in the physical organization of the complex. The resultant diverse
      morphologies are due to multiple factors, including the method for initial
      isolation of follicles, the culture substrate, and hormones and other factors
      added into the medium. It is important to find an optimal combination of such
      factors involved in the process to facilitate future research efforts.

PMID- 21729196
TI  - Metabolism of microbial nitrogen in ruminants with special reference to nucleic
      acids.
AB  - Characteristically the metabolism of microbial nitrogen (N) compounds in
      ruminants involves the degradation of dietary N and synthesis of microbial
      protein (MP), compounds including a small amount of peptides and free amino
      acids, which may account for 75-85% of total N and the remainder are nucleic
      acids (NA: DNA and RNA). Generally rumen microbes contain 10-25% NA-N of the
      total N while 70-80% is in the form of RNA. This paper describes the degradation
      and synthesis of NA in the rumen and their fate in the lower digestive tracts.
      Their physiological and nutritional significance in different types of ruminant
      animals is also discussed. The research works on NA metabolism in ruminants has
      been mainly on metabolism of purines after rumen microbial digestion and
      absorption in the lower gut. Subsequently, the fate of absorbed purines has been
      intensively investigated to assess the extent of MP synthesis in the rumen. The
      method for predicting ruminal synthesized MP and subsequently digested MP has
      been proposed using urinary purine derivative (PD) excretion in sheep and cattle
      fed on ordinary feed. The latter approach has now been adopted for calculation of
      protein supply in some feeding standards, although there are still difficulties
      in predicting representative samples of rumen microbes, and also uncertainties in
      variations of non-renal and endogenous purine losses.

PMID- 21729197
TI  - A proximal genomic region of mouse chromosome 10 contains quantitative trait loci
      affecting fatness.
AB  - Body weight and fatness are quantitative traits of agricultural and medical
      importance. In previous genome-wide quantitative trait locus (QTL) analyses, two
      QTLs for body weight and weight gain at an early postnatal growth period were
      discovered on mouse chromosome 10 from a gene pool of wild subspecies mice, Mus
      musculus castaneus. In this study, we developed a congenic strain with an
      approximately 63-Mb wild-derived genomic region on which the two growth QTLs
      could be located, by recurrent backcrossing to the common inbred strain C57BL/6J.
      We compared body weights at 1-10 weeks of age, body weight gains at 1-3, 3-6 and
      6-10 weeks, internal organ weights and body lengths between the congenic strain
      developed and C57BL/6J. Unfortunately, no effects of the two growth QTLs on body
      weights and weight gains were confirmed. However, at least two new QTLs affecting
      fatness traits were discovered within the introgressed congenic region. The wild
      derived allele at one QTL increased body mass index, whereas at another one it
      decreased white fat pad weight and adiposity index. Thus, the congenic mouse
      strain developed here is a useful model animal for understanding the genetic and
      molecular basis of fat deposition in livestock as well as humans.

PMID- 21729198
TI  - Establishment and characterization of a fibroblast cell line derived from
      Mongolian sheep.
AB  - The Mongolian sheep ear marginal tissue fibroblast cell line (MSF32) from 32
      samples was successfully established by using primary explants technique and cell
      cryoconservation technology. MSF32 cells were adherent, with a population
      doubling time of 28.2 h. Chromosome analysis showed that >90.2% of cells were
      diploid (2n=54) prior to cell passage 4. Isoenzyme analyses of lactate
      dehydrogenase and malate dehydrogenase showed that the MSF22 cells had no cross
      contamination with other species. Tests for cell line contamination with
      bacteria, fungi, viruses and mycoplasmas were also negative. Plasmids encoding
      the fluorescent proteins pEGFP-N3, pEGFP-C1, pECFP-N1, pECFP-mito, pDsRed1-N1 and
      pEYFP-N1 were transfected into cells to study exogenous gene expression in the
      cells. The plasmid transfection efficiency was between 12.3% and 63.3%. Every
      index of the MSF32 cell line meets all the standard quality controls of American
      Type Culture Collection (ATCC). Not only has the genetic resources of the
      Mongolian sheep been preserved at the cell level, but also valuable materials had
      been provided for genome, postgenome and somacloning research.

PMID- 21729199
TI  - Allele-specific PCR typing and sequencing of the mitochondrial D-loop region in
      four layer breeds.
AB  - This study aimed to investigate the ability of single nucleotide polymorphism
      (SNP) haplotypes in chicken mtDNA for presumption of the origins of chicken meat.
      We typed five SNPs of the D-loop region in mtDNA by allele-specific PCR (AS-PCR)
      in 556 hens, that is 233 White Leghorn (WL), 50 Dekalb-TX35 (D-TX), 140 Barred
      Plymouth Rock (BPR) and 133 Rhode Island Red (RIR) kept in the National Institute
      of Livestock and Grassland Science (NILGS, Tsukuba, Japan). Five haplotypes were
      observed among those chickens by AS-PCR. WL, D-TX, BPR and RIR displayed three,
      two, one and four SNP haplotypes, respectively. By a combination of the
      haplotypes by AS-PCR and the breeds, these chickens were classified into 10
      groups. After the D-loop was sequenced in two chickens from every group (20
      individuals), 15 SNP sites (including one insertion) and eight sequence
      haplotypes were observed. In conclusion, haplotype variation was observed in and
      among the layer breeds of the NILGS. This study demonstrates that SNP haplotypes
      in mtDNA should be appropriate for the presumption of the origins of chicken
      meat.

PMID- 21729200
TI  - Oocytic expression of zona pellucida protein ZP4 in Japanese quail (Coturnix
      japonica).
AB  - The avian perivitelline layer, an extracellular matrix homologous to the zona
      pellucida (ZP) of mammalian oocytes, is composed mainly by zona pellucida gene
      family glycoproteins. Our previous studies in Japanese quail have demonstrated
      that the matrix's components, ZP3 and ZPD, are synthesized in ovarian granulosa
      cells. Another component, ZP1, is synthesized in the liver. Recently, we
      demonstrated that another minor constituent, ZP2 is produced in the oocytes of
      the immature follicles. In the present study, we report the isolation of
      complementary DNA encoding quail ZP4 and its expression and origin in the female
      birds. By ribonuclease protection assay and in situ hybridization, we
      demonstrated that ZP4 transcripts were transcribed in the oocytes of small white
      follicles. The expression level of ZP4 decreased dramatically during follicular
      development, and the highest expression was observed in the small white
      follicles. Western blot analysis using the specific antibody against ZP4
      indicated that the immunoreactive 58.2 kDa protein was present in the lysates of
      the small white follicles. These results demonstrate for the first time that the
      avian ZP4 is expressed in the oocyte, and that the expression pattern of the gene
      is similar to that of ZP2.

PMID- 21729201
TI  - Constant transmission of mitochondrial DNA in intergeneric cloned embryos
      reconstructed from swamp buffalo fibroblasts and bovine ooplasm.
AB  - Although interspecies/intergeneric somatic cell nuclear transfer (iSCNT) has been
      proposed as a tool to produce offspring of endangered species, conflict between
      donor nucleus and recipient cytoplasm in iSCNT embryos has been identified as an
      impediment to implementation for agricultural production. To investigate the
      nuclear-mitochondrial interactions on the developmental potential of iSCNT
      embryos, we analyzed the mtDNA copy numbers in iSCNT embryos reconstructed with
      water buffalo (swamp type) fibroblasts and bovine enucleated oocytes (buffalo
      iSCNT). As controls, SCNT embryos were derived from bovine fibroblasts (bovine
      SCNT). Buffalo iSCNT and bovine SCNT embryos showed similar rates of cleavage and
      development to the 8-cell stage (P>0.05). However, buffalo iSCNT embryos did not
      develop beyond the 16-cell stage. Both bovine and buffalo mtDNA content in
      buffalo iSCNT embryos was stable throughout the nuclear transfer process, and
      arrested at the 8- to 16-cell stage (P>0.05). In bovine SCNT embryos that
      developed to the blastocyst stage, mtDNA copy number was increased (P<0.05). In
      conclusion, both the donor cell and recipient cytoplast mtDNAs of buffalo iSCNT
      embryos were identified and maintained through the iSCNT process until the 8-16
      cell stage. In addition, the copy number of mtDNA per embryo was a useful monitor
      to investigate nuclear-mitochondrial interactions.

PMID- 21729202
TI  - Contribution of hypoxia-inducible factor-1alpha to transcriptional regulation of
      vascular endothelial growth factor in bovine developing luteal cells.
AB  - Vascular endothelial growth factor (VEGF)-dependent angiogenesis is crucial for
      corpus leteum formation and their functional maintenance in mammalian ovaries.
      The present study was designed to test the hypothesis that hypoxia-inducible
      factor (HIF)-1alpha-mediated transcriptional activation contributes to the
      increased expression of VEGF gene in response to hypoxia in the bovine developing
      luteal cells (LCs). By real-time RT-PCR analysis, VEGF messenger RNA (mRNA)
      expression was found to significantly increase under hypoxia or treatment with
      desferrioxamine (DFX), cobalt chloride (CoCl(2)) or even N-carbobenzoxyl-L
      leucinyl-L-leucinyl-L-norvalinal (MG-132), while these increased VEGF mRNA
      expressions could also be blocked by ferrous ammonium sulfate (FAS) or cis
      element oligodeoxynucleotide (dsODN) transfection under hypoxia. Further analysis
      also found that these changes of VEGF mRNA were consistent with HIF-1alpha
      expression or HIF-1 activity. Taken together, our results indicate that VEGF is
      transcriptionally activated by hypoxia through HIF-1alpha-mediated mechanisms in
      LCs. This hypoxia-induced transcriptional activation may be one of the important
      mechanisms mediating the increase of VEGF expression in developing LCs during
      mammalian corpus leteum formation.

PMID- 21729203
TI  - Observations on hand-mating behaviors, several physiological and hematological
      parameters in Turkish dairy goats.
AB  - The aims of this study were to examine hand-mating behavior of doe and buck and
      relationships of courtship behavior and physiological and hematological traits
      according to gestation results. Duration from beginning of observation until
      mating (M-C), duration between two copulations (C-C) and courtship behavioral
      index value of each sex (CBIVD; courtship behavioral index value of doe, CBIVB;
      courtship behavioral index value of buck) and mounting behavior of buck, were
      observed. Experience of doe was affected of CBIVD and CBIVB (P=0.01 and P=0.01,
      respectively). Bucks mounted significantly higher times on experienced does than
      on inexperienced ones (P=0.00). On the other hand service number decreased with
      an increase in M-C (P=0.00). Elevated service number was observed with increased
      mounting frequency of buck (P=0.03). There were strong correlations between CBIVD
      and CBIVB (r=0.48, P=0.00). Pregnancy was not influenced by vaginal pH value.
      Does, which gave multiple births, had higher vaginal pH (P=0.05). Rectal
      temperature difference of doe had no influence on success of mating and birth
      type. On the other hand, birth type was affected by rectal temperature difference
      of buck. There was no significant difference of hematological parameters
      according to mating results. Hemoglobin, red blood cell count and mean
      corpuscular hemoglobin concentration values were higher in single births and mean
      cell volume value was lower in single births.

PMID- 21729204
TI  - Fermentation characteristics and microorganism composition of total mixed ration
      silage with local food by-products in different seasons.
AB  - Total mixed ration (TMR) silage in different seasons was prepared with apple
      refuse, orchardgrass hay, orchardgrass silage, corn silage and a commercial
      compound feed in Tohoku, Japan, and with tofu cake, brewers' grains, tall fescue
      hay, Sudangrass hay, timothy hay, alfalfa hay and a commercial compound feed in
      Shikoku, Japan, respectively, and their fermentation quality and microorganism
      composition were evaluated. In Tohoku, the TMR silage in spring, autumn and
      winter displayed poor quality, with pH value above 4.7, and the harmful
      microorganisms such as escherichia, yeasts and molds were detected even after 60
      days of ensiling; but the TMR silage in summer was well preserved and the
      escherichia were too few to count after 7 days of ensiling. In Shikoku, the TMR
      silage in all seasons was well preserved, with low pH, high lactic acid contents,
      and escherichia, yeasts and molds were consistently at or below the detectable
      numbers after 7 days of ensiling. The results showed that the TMR silage could
      not produce sufficient lactic acid to improve silage quality under low
      temperature conditions. Therefore, it is necessary to develop preparation
      techniques of promoting the lactic acid fermentation for TMR silage in cold
      seasons.

PMID- 21729205
TI  - Effects of amino acids infused into the vein on ghrelin-induced GH, insulin and
      glucagon secretion in lactating cows.
AB  - To investigate the effects of amino acids on ghrelin-induced growth hormone (GH),
      insulin and glucagon secretion in lactating dairy cattle, six Holstein cows were
      randomly assigned to two infusion treatments in a cross-over design. Mixture
      solution of amino acids (AMI) or saline (CON) was continuously infused into the
      left side jugular vein via catheter for 4 h. At 2 h after the start of infusion,
      synthetic bovine ghrelin was single injected into the right side jugular vein
      through the catheter. Ghrelin injection immediately increased plasma GH, glucose
      and non-esterified fatty acids (P<0.05) with no difference between both
      treatments. Additionally, plasma insulin and glucagon concentrations were
      increased by ghrelin injection in both treatments. The peak value of plasma
      insulin concentration was greater in AMI compared with CON (P<0.05). Plasma
      glucagon concentration showed no difference in the peak value reached at 5 min
      between both treatments, and then the plasma levels in AMI compared with CON
      showed sustained higher values (P<0.05). After plasma glucose concentration
      reached the peak, the decline was greater in AMI compared with CON (P<0.05).
      These results showed that the increased plasma amino acids may enhance ghrelin
      action which in turn enhances insulin and glucagon secretions in lactating cows.

PMID- 21729206
TI  - Effect of dietary addition of seaweed and licorice on the immune performance of
      pigs.
AB  - In pig production, dietary additive antibiotics are usually used for growth
      stimulation and disease prevention, although there is public concern about the
      increased incidence of resistant antibiotics and food safety. It is possible that
      such antibiotics might be replaced by naturally derived products such as seaweed
      and licorice. In this study, we evaluated the effect of dietary addition of
      seaweed and licorice on enhancing the immune function in swine. The animals of
      each group (eight animals per group) were sensitized at day 42 and 49, and the
      immunoglobulin production and the expression of cytokines were detected by the
      ELISA and real-time PCR. As the results, saliva IgA production of the seaweed
      treated group increased around five times compared to that of control (day 56).
      Delayed hypersensitivity reaction and IgG production of the seaweed-treated group
      increased around 1.8-2.0 times. In addition, enhanced saliva IgA production was
      detected at day 50 (around two times) and day 51 (around five times) by the
      licorice treatment, and lower expression level of tumor necrosis factor-alpha
      messenger RNA at day 51 (around 1/25) was observed in the licorice treatment. We
      conclude that the replacement of antibiotics by naturally derived dietary
      additives might be feasible for immune system enhancement.

PMID- 21729207
TI  - Efficacy of probiotics from anaerobic microflora with prebiotics on growth
      performance and noxious gas emission in growing pigs.
AB  - We investigated the effect of probiotics from anaerobic microflora with
      prebiotics (synbiotics) on growth performance, noxious gas emission and fecal
      pathogenic bacteria populations in growing pigs. The basal diet, which contained
      approximately 25% corn, 24% whey, 12% wheat and 12% soybean meal, was
      supplemented alternatively with 0.15% antibiotics (US diet), prebiotics and 0.2%
      probiotics from anaerobic bacteria (BS diet), yeast (YS diet), mold (MS diet) or
      compounds (CS diet). One hundred and fifty pigs were fed an experimental diet for
      15 days. Although the growth performance was not affected by supplemental
      synbiotics, the BS group showed higher dry matter and crude protein
      digestibility. The BS group decreased fecal ammonia and amine gas emissions, and
      increased fecal acetate gas emission compared with the US group. All synbiotics
      groups decreased in fecal propionate gas emission. Fecal Escherichia coli
      population was lower in the synbiotics groups than in the US group. Therefore,
      the results of the present study suggest that synbiotics exert similar effects
      with antibiotics on the nutrient digestibility and fecal microflora composition
      in growing pigs. Moreover, synbiotics can also decrease the fecal noxious gas
      emission in growing pigs.

PMID- 21729208
TI  - Tissue distribution of albumin-glucose advanced glycation end products
      administrated to chickens.
AB  - Glycation (Maillard reaction) starts from non-enzymatic amino-carbonyl reaction
      binding carbonyl group of reducing sugars to amino group of amino acids. The
      amino-carbonyl reaction leads to the formation of the stable Amadori product,
      which ultimately forms advanced glycation end products (AGE). Acceleration of
      glycation during hyperglycemia increases the production and accumulation of AGE,
      which is implicated in the gradual development of diabetic complications in
      diabetes mellitus. Avian species offers the great advantage of providing animal
      models for diabetology because high blood glucose concentration should accelerate
      to generate high concentration of AGE. In the present study, radioactive AGE was
      prepared from chicken serum albumin and (14)C-glucose. Radioactive AGE was
      administrated to examine the tissue distribution of AGE in chickens.
      Administration of radioactive AGE into the circulation of chickens revealed that
      AGE accumulated into specific tissues, liver, spleen and kidney, which have the
      function for clearing exogenous substances and endogenous metabolic waste
      products.

PMID- 21729209
TI  - Effect of indigestible sugars on nitrogen utilization in adult rabbits.
AB  - To determine the effects of indigestible sugars on the digestibilities of
      nutrients and utilization of nitrogen (N) in adult male rabbits, 12 rabbits with
      or without a collar that prevented cecotrophy were fed experimental diets for 8
      days, comprising 3 days for adaptation and 5 days for collection of feces and
      urine. The experimental diets were formulated by adding D-mannitol or citrus
      pectin to a commercial diet at 60 g/kg. In the rabbits allowed cecotrophy,
      mannitol increased the absorption of crude ash but did not significantly alter
      the digestibilities of crude protein (CP), dry matter and acid-detergent fiber.
      By contrast, the digestibility of CP was decreased by pectin. The ratios of
      retained N to consumed N and absorbed N were elevated by mannitol. In the rabbits
      prevented from cecotrophy, mannitol had no effect on N retention, but increased
      the N content of cecotrophs (soft feces) and the ratio of the N content of
      cecotrophs to consumed N. Pectin did not have any significant influences on N
      retention and the N content of cecotrophs. These results suggest that D-mannitol
      stimulates cecal microbial proliferation, thereby improving N utilization in
      rabbits.

PMID- 21729210
TI  - Evaluation of the heat-killed and dried cell preparation of Enterococcus faecalis
      against villous atrophy in early-weaned mice and pigs.
AB  - Early weaning induces villous atrophy in the small intestine (SI) of piglets.
      Oral administration of live lactic acid bacteria (LAB) can improve villous
      shortening. In this study, we evaluated the oral administration of a heat-killed
      and dried cell preparation of Enterococcus faecalis (a LAB) strain EC-12 against
      villous atrophy in early-weaned mice (Experiment 1) and pigs (Experiments 2 and
      3). Twelve 16-days-old mice were divided into two groups in Experiment 1: gavage
      of EC-12 (10 mg/kg body weight (BW)/day), or control. On day 21, SI was
      collected. Eighteen 21-day-old pigs were divided into two groups in Experiment 2:
      gavage of EC-12 (10 mg/kg BW/day), or control. After 10 days, the villous height
      of jejunum was measured. Six 21-day-old pigs were divided into two groups in
      Experiment 3: the basal diet supplemented with EC-12 at 0.05%-fed group, or the
      basal diet-fed group. After 10 days, the villous height of jejunum was measured.
      The villous heights in SI were significantly higher by EC-12 administration in
      all experiments. EC-12 successfully improved the villous atrophy in the early
      weaned mice and pigs when EC-12 was administered orally.

PMID- 21729211
TI  - Immunohistochemical and ultrastructural characterization of the ovarian surface
      epithelium of Japanese quail (Coturnix japonica).
AB  - Contrary to humans, most ovarian tumors in other species do not arise from the
      ovarian surface epithelium but are of follicular-, stromal- or germ-cell origin.
      One of the few species where ovarian cancer arises from the ovarian surface
      epithelium (OSE) is chicken (Gallus domesticus). Little is known about the
      morphology of the OSE in other avian species. In our study we analyzed the OSE
      morphology of Japanese quail (Coturnix japonica) using ultrastructural and
      histochemical techniques. Carbohydrate residues have been studied by using a
      panel of fluorescein isothiocyanate labeled lectins. Japanese quails are commonly
      used animal models in biomedical research as their housing is comparatively
      inexpensive and they show a short generation interval. Our ultrastructural and
      histochemical results demonstrate that the quail ovarian surface epithelium shows
      characteristic features which resemble the epithelia of both chicken and human.
      Additionally, the ovarian surface epithelium of the Japanese quail contains
      cytokeratin as well as vimentin intermediate filaments in their cytoplasm.
      Therewith and among other parts the quail OSE shows many characteristic features
      also seen in those of humans, which may qualify quail's ovary as a potential
      animal model for human ovarian carcinomas.

PMID- 21729212
TI  - Effect of intracerebroventricular injections of prolactin-releasing peptide on
      prolactin release and stress-related responses in steers.
AB  - Some evidence suggests that there might be a species difference in the effect of
      intracerebroventricularly administered (ICV) prolactin-releasing peptide (PrRP)
      between rodents and sheep. We compared the levels of cortisol (CORT) and
      prolactin (PRL), rectal temperature (RT) and behavioral responses to ICV bovine
      PrRP (bPrRP) in steers. ICV bPrRP (0.2, 2 and 20 nmol/200 uL) tended to evoke a
      dose-related increase in CORT concentrations and 0.2 nmol of bPrRP induced
      transient increase in PRL concentrations. A significant time-treatment
      interaction was observed for the percent change of CORT (P<0.05) and PRL (P<0.05)
      from pre-injection value. The time-treatment interaction for changes in RT was
      not significant (P=0.50). There tended to be a difference among the four
      treatments in terms of maximum change in RT from the pre-injection value between
      0 and 90 min (P<0.1). Stress-related behavioral signs were not observed in the
      present experiment. These findings indicate that ICV bPrRP increased CORT and PRL
      levels, suggesting that central PrRP might participate in controlling the
      hypothalamo-pituitary-adrenal axis and PRL release in cattle, unlike sheep. In
      contrast, central PrRP is unlikely to be involved in controlling the behavior of
      this species because ICV bPrRP did not induce marked changes in their behavior.

PMID- 21729213
TI  - Changes in oxidative status in periparturient dairy cows in hot conditions.
AB  - We investigated the changes in the plasma concentrations of oxidative stress
      markers in periparturient dairy cows in hot conditions. This study was performed
      on 10 cows from day -5 to day 10 after parturition. The experimental duration was
      divided into three periods: period 1 (5 days before parturition); period 2 (5
      days after parturition); and period 3 (from day 6 to day 10 after parturition).
      The average rectal temperature in the cows during the experimental period was
      more than 39  degrees C. Plasma aspartate aminotransferase activities in periods
      2 and 3 were higher than that in period 1 (P<0.05). Blood urea nitrogen
      concentration in period 3 was lower than those in periods 1 and 2 (P<0.05). The
      total ascorbic acid concentration in the plasma in period 2 was greater than
      those in periods 1 and 3 (P<0.05). Thiobarbituric acid reactive substances
      (TBARS) concentrations in periods 2 and 3 were greater than that in period 1
      (P<0.05). TBARS concentration was positively correlated with aspartate
      aminotransferase activity (P<0.05). These results suggested that oxidative stress
      increased in cows after parturition under hot climatic conditions.

PMID- 21729214
TI  - Japanese consumer categorisation of beef into quality grades, based on Meat
      Standards Australia methodology.
AB  - The objective was to evaluate the sensory categorisation of beef by Japanese
      consumers, based on Meat Standards Australia methodology. Various cuts of beef,
      with a wide range of quality (from Australian and Japanese cattle) and three
      cooking methods (grill, yakiniku, shabu shabu), were evaluated by 1620 Japanese
      consumers in Tokyo and Osaka. Consumers rated each sample for four sensory
      attributes (tenderness, juiciness, flavor and overall satisfaction), then
      selected one of four grades (unsatisfactory/2-star, good everyday/3-star, better
      than everyday/4-star, and premium quality/5-star), based on the quality of the
      beef within each cooking method. Meat quality scores, denoted as MQ4 scores
      (weighted combination of the four sensory attributes) were calculated from the
      Japanese consumer test results, to describe the Japanese consumer rating of beef.
      The distribution of the Japanese consumer MQ4 scores showed a clear distinction
      between grades, with the majority of scores being included within the boundaries
      of each grade. The MQ4 score allocated approximately 64% of the samples to their
      correct consumer grades. The MQ4 score showed potential to be used as a tool in
      developing and monitoring a consumer-focused grading system that is able to
      predict Japanese consumer satisfaction of individual beef cuts prepared by
      different cooking methods.

PMID- 21729215
TI  - Investigation into the durability of washed rice straw for equine bedding and the
      repetitive use of washing water.
AB  - The present experiment investigated durability during the repetitive use of
      washed rice straw, as bedding material, and washing water as a model study.
      Residual nitrogen levels, elasticity, and water suction rates for washed rice
      straw-adhered urea were measured. In addition, outflow levels of nitrogen and
      mineral ions (Na(+), NO(2)(-) + NO(3)(-), SO(4)(2-), PO(4)(3-), Cl(-)) for
      washing water were measured to determine durability. Nitrogen levels of rice
      straw significantly (P<0.05) decreased after two washings. There was no
      significant change in elasticity of repetitively used rice straw. Suction rates
      of rice straw after the second and third washings increased significantly
      (P<0.05) compared to the first time. With regard to the number of washings, the
      mineral ion outflow level in the washing water for nitrogen, Na(+), NO(2)(-) +
      NO(3)(-) and PO(4)(3-) after each washing was not significant. However, nitrogen
      outflow level tended to decrease after the third washing. SO(4)(-) and Cl(-) did
      significantly decrease (P<0.05) with the number of washings. In this study, it
      was considered that rice straw and washing water could be used repetitively three
      times. Furthermore, in order to maintain effluent standards, washing water from
      the first washing needs to be processed in a septic tank.

PMID- 21729216
TI  - Characterization and partial purification of a bacteriocin-like substance
      produced by thermophilic Bacillus licheniformis H1 isolated from cow manure
      compost.
AB  - The production and partial characterization of bacteriocin-like substances (BLSs)
      produced by bacteria isolated from cow manure compost were investigated. Eight
      BLS producers, which exhibited inhibitory activity against pathogenic bacteria,
      were isolated from cow manure compost at different stages of the composting
      process. The pile temperature ranged from 9.1  degrees C to 73.2  degrees C. The
      BLSs showed thermostability, but the BLS producers were not thermostable except
      for the H1 producer. Thermophilic Bacillus licheniformis H1 was further
      characterized. The culture supernatant of B. licheniformis H1 exhibited
      antagonistic activity against various species of Gram-positive bacteria such as
      Listeria monocytogenes ATCC19111 but not against Gram-negative bacteria except
      Pseudomonas fluorescens ATCC11251. Inactivation of bacteriocin-like activity by
      alpha-chymotrypsin, trypsin, and papain was highly significant (P<0.001). The BLS
      was found to be stable under a pH range from 3 to 9 and at temperatures up to 75 
      degrees C for 60 min, but it lost activity after being autoclaved at 121  degrees
      C for 15 min. The optimum production of BLS by B. licheniformis H1 was obtained
      at a temperature of 55  degrees C. Sodium dodecyl sulfate - polyacrylamide
      electrophoresis analysis of concentrated partially purified supernatants
      collected after resting the bacterial cells at 55  degrees C revealed a
      bacteriocin-like protein with a molecular mass of approximately 3.5 kDa. This
      study is the first report of a BLS from thermophilic B. licheniformis with an
      animal compost origin.

PMID- 21729217
TI  - Comparison of feeding systems: feed cost, palatability and environmental impact
      among hay-fattened beef, consistent grass-only-fed beef and conventional marbled
      beef in Wagyu (Japanese Black cattle).
AB  - The objective of this article is to compare feed cost, palatability and
      environmental impacts among feeding systems of high concentrate (HC), high hay
      (HH) and grass-only-fed (Gof) groups. Feed cost was the sum of costs paid for
      feed intake times the price of feed per kilogram. Palatability was measured by a
      panel taste test using HH and Gof beef and analyzed for differences.
      Environmental impacts were calculated based on 1 kg of Japanese beef yield of
      CO(2) equivalents (eq) and animal end weights at each feeding stage. Results
      showed that the HH and Gof feeding systems could significantly reduce feed costs
      by approximately 60% and 78%, respectively, from the HC. In the panel taste test,
      50% and 47.50% of panelists indicated that HH beef was 'extremely delicious' and
      'acceptable,' respectively, while 15% indicated that Gof beef was 'extremely
      delicious'; 62.50% indicated that Gof beef was 'acceptable.' Environmental
      impacts of each feeding system in terms of CO(2) equivalents (eq) were 9.32, 6.10
      and 2.04 tonnes of eq for the HC, HH and Gof, respectively. The HH was an
      economical system that produced moderate impacts on the environment and had
      impressive taste.

PMID- 21729218
TI  - Survival of embryos and calves derived from somatic cell nuclear transfer in
      cattle: a nationwide survey in Japan.
AB  - To obtain data concerning the survival of embryos and calves derived from somatic
      cell nuclear transfer (SCNT) in Japan, a nationwide survey was carried out in
      April, 2009. As a result, data concerning 3264 embryo transfers (ETs) with SCNT
      embryos which produced 301 calves were accumulated and their survival was
      analyzed. The present survey revealed that survival rates of transferred bovine
      embryos and produced calves derived from SCNT had not improved over a decade
      (1998-2007). A remarkable feature of the pregnancies with SCNT embryos was a high
      incidence of spontaneous abortions. When the decade was divided by the occurrence
      of bovine spongiform encephalopathy (BSE) in 2001, significant decreases in the
      'after BSE' period (2002-2007) were observed in the percentages of calves born
      (P<0.01), calves living at birth (P<0.05), calves living for 24 h (P<0.05) and 6
      months (P<0.01). Abortions that occurred during 61-99 days after ETs were
      significantly increased (P<0.01) in the 'after BSE' period. Certain kinds of
      regeneration that occurred in oocytes during the 15-20 h of storage of bovine
      ovaries at 10-15  degrees C as a part of BSE inspection might have had some
      negative effects on SCNT embryos when these oocytes were used as recipients of
      SCNT.

PMID- 21729219
TI  - Genistein attenuates genioglossus muscle fatigue under chronic intermittent
      hypoxia by down-regulation of oxidative stress level and up-regulation of
      antioxidant enzyme activity through ERK1/2 signaling pathway.
AB  - OBJECTIVE: This study aims to investigate the effects of genistein on contractile
      properties of genioglossus under chronic intermittent hypoxia (CIH) conditions
      and its relationship with oxidative stress, antioxidant enzyme, and ERK1/2
      signaling pathway. MATERIALS AND METHODS: Fifty female Sprague-Dawley rats were
      randomly divided into five groups 1 week after ovariectomy: the normal control
      group, the CIH group, the CIH with low-dose, medium-dose, and high-dose genistein
      groups. Rats in the latter four groups were exposed to CIH for 5 weeks. Twitch
      tension, tetanic tension, and fatigue resistance of genioglossus were
      investigated. Malondialdehyde (MDA) and mitochondrial reactive oxygen species
      (ROS), enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase
      (GPx), catalase (CAT), and ERK1/2 were detected. RESULTS: Muscle fatigue
      resistance and enzymatic activity of GPx, CAT, and SOD were reduced after CIH
      exposure and improved by different doses of genistein at different degrees. CIH
      increased the level of ROS and MDA, and they were returned to normal by
      genistein. The expression of phospho-ERK1/2 is opposite to the changes in muscle
      fatigue resistance. CONCLUSION: Chronic intermittent hypoxia decreases fatigue
      resistance of genioglossus, and genistein treatment reverses the fatigability of
      genioglossus by down-regulation of oxidative stress level and up-regulation of
      antioxidant enzymatic activity probably through ERK1/2 signaling pathway.

PMID- 21729220
TI  - A novel mutation in the OFD1 (Cxorf5) gene may contribute to oral phenotype in
      patients with oral-facial-digital syndrome type 1.
AB  - BACKGROUND: Oral-facial-digital syndrome (OFDS) type 1 (OFD1) is an X-linked
      dominant condition associated with embryonic male lethality. It almost always
      affects the oral cavity, face, and digits. It is considered to be a ciliopathy
      caused by mutations in the OFD1 gene. A variety of mutations have been described,
      and a genotype-phenotype correlation has been suggested. OBJECTIVE AND METHODS:
      The proband was an 8-year-old Spanish girl with suspected OFD1. We extended the
      pedigree to three proband's generations, performing a thorough physical
      examination and screening for OFD1 mutations in nine individuals. RESULTS: The
      proband, her mother, and her sister showed oral findings consistent with OFD1.
      Ultrasound evaluation revealed the existence of renal cysts only in the proband's
      mother. The rest of the family (all male) had no relevant morphological
      abnormalities. A single-base deletion in exon 16 of OFD1 (c.2183delG) leading to
      a frameshift was detected in the proband, her mother, and her sister. CONCLUSION:
      Because all three women had a similar oral phenotype, this new mutation might be
      involved in the development of the OFD1 oral manifestations. In cases of OFDS,
      physical examination (including the oral cavity and renal function) and genetic
      screening of the probands and their relatives are mandatory.

PMID- 21729221
TI  - Does supervision improve health worker productivity? Evidence from the Upper East
      Region of Ghana.
AB  - OBJECTIVES: To assess whether supervision of primary health care workers improves
      their productivity in four districts of Northern Ghana. METHODS: We conducted a
      time-use study during which the activities of health workers were repeatedly
      observed and classified. Classification included four categories: direct patient
      care; documentation and reporting; staff development and facility operations; and
      personal time. These data were supplemented by a survey of health workers during
      which patterns of supervision were assessed. We used logistic regression models
      with health facility fixed effects to test the hypothesis that supervision
      increases the amount of time spent providing direct patient care (productivity).
      We further investigated whether these effects depend on whether or not
      supervision is supportive. RESULTS: Direct patient care accounted for <25% of
      observations. In bivariate analyses, productivity was higher among midwives and
      in facilities with a high volume of care. Supervisory visits were frequent in
      those four districts, but only a minority of health workers felt supported by
      their supervisors. Having been supervised within the last month was associated
      with a significantly higher proportion of time spent on direct patient care (OR =
      1.57). The effects of supervision on productivity further depended on whether the
      health workers felt supported by their supervisors. CONCLUSION: Supportive
      supervision was associated with increased productivity. Investments in
      supervision could help maximize the output of scarce human resources in primary
      health care facilities. Time-use studies represent an objective approach in
      monitoring the productivity of health workers and evaluating the impact of health
      system interventions on human resources.

PMID- 21729222
TI  - Prevalence and risk factors of Plasmodium falciparum infections in pregnant women
      of Luanda, Angola.
AB  - Pregnant women are at increased risk of malaria, but in Angola, epidemiologic
      data from this group is almost inexistent. We conducted a cross-sectional study
      to determine the prevalence and risk factors of Plasmodium falciparum infections
      in 567 pregnant Angolan women living in Luanda province. One in five women had P.
      falciparum at delivery, diagnosed by PCR assay. Age, residence and history of
      malaria during pregnancy were significantly associated with P. falciparum
      infection, but gravidity and use of anti-malarial drugs were not. Placental
      infections were significantly more common in women <=18 years old and in
      primigravidae, but we could not correlate placental infections with poor
      pregnancy outcomes. These findings are relevant to malaria control policies in
      Luanda, Angola.

PMID- 21729223
TI  - Rediscovering nursing: a study of overseas nurses working in Western Australia.
AB  - The shortage of nurses worldwide has taken its toll on the Australian healthcare
      system and, as a result, there is an increased migration of overseas-qualified
      nurses, some of them with a non-English-speaking background. Despite Australia's
      regulations that assess the eligibility for nursing registration, many migrant
      nurses who have been successful in gaining their nursing license feel only
      partially prepared to work. This article presents the findings of a study, based
      on Husserlian phenomenology, that describes the work experience of 13 female
      nurses who were working in Western Australia, Australia. The participants, who
      could recognize the core components of nursing, were taken aback by the way that
      nursing is practised in Western Australia. The major differences that they
      encountered were related to clinical skills, holistic care, the work dynamic with
      doctors and patients, and the overall societal status of the nursing profession.
      As a result, they had to adjust their practice to conform to the new work
      environment. In this study, the participants elaborated on some positive and some
      not-so-positive aspects of their experiences in their endeavor to integrate into
      the Western Australian metropolitan hospital setting.

PMID- 21729224
TI  - Older people's mortality index: development of a practical model for prediction
      of mortality in nursing homes (Kahrizak Elderly Study).
AB  - AIMS: In the elderly, mortality prediction models are important for clinical
      decision-making and planning of services required. METHODS: A total of 247
      Kahrizak Charity Foundation (KCF) residents aged >= 65 years were followed up for
      approximately 39 months. At the baseline, the questionnaires of Barthel Index
      (BI), Mini-Mental State Examination, Geriatric Depression Scale, Mini Nutritional
      Assessment and Norton Index was given. Medical history was recorded and
      anthropometric values were also measured at the baseline. Fasting blood samples
      were collected at baseline. Mortality and its causes were recorded during the
      study. RESULTS: A total of 30% (74) of participants died during the study. The
      variables that had a significant association with mortality in the Cox regression
      hazard model were entered into the principal components analysis (PCA). The older
      people's mortality index (OPMI) was developed by four variables extracted from
      PCA, including BI, age, hemoglobin and mid-arm circumference. Cut-points of these
      components were calculated using ROC curve analysis. Based on neural network
      analysis, there was no significant difference in relative importance of OPMI
      components. OPMI was correlated to mortality (r = -.351, P = 0.000) and survival
      (r = -0.355, P = 0.000). OPMI score was defined as the number of adverse
      predictors present. An increasing hazard ratio for mortality was observed from
      scores 1 to 4 (2.10, 4.56, 7.12 and 13.85, respectively). CONCLUSION: Our
      suggested model could predict mortality in KCF residents well. The new developed
      model could be a practical, easy and non-expensive index for mortality prediction
      in elderly care facilities.

PMID- 21729225
TI  - Subarachnoid hemorrhage in elderly: advantages of the endovascular treatment.
AB  - AIM: Subarachnoid hemorrhage (SAH) from aneurysm rupture accounts for
      approximately 3% of all strokes. A significant improvement in surgery and
      endovascular procedures has reduced mortality and morbidity. Nowadays,
      endovascular treatment is a viable alternative to conservative treatment in
      elderly patients. We designed a retrospective observational study on all
      endovascular procedures carried out in our department in order to evaluate the
      outcome in elderly patients compared with a younger cohort. METHODS: A total of
      378 patients with aneurysmal SAH were treated with detachable platinum coils in
      our department (1994-2009). Of these, 310 patients were aged 20-69 years and 68
      were aged over 70 years. Data were stratified according to Hunt-Hess (H-H) grade
      at admission. The mean follow up was 4.8 years. The final outcome was evaluated
      through the Glasgow Outcome Scale (GOS). RESULTS: We observed a favorable outcome
      (GOS 5-4) in both groups of patients admitted with moderately good clinical
      conditions (H-H 1-3), with no statistically significant difference. In contrast,
      in the case of H-H grade at admission > 3, we observed a statistically
      significant poor outcome in elderly patients. CONCLUSIONS: We consider the
      endovascular treatment as first choice for elderly patients presenting with a
      good H-H grade at admission. Quick functional recovery and reduced
      hospitalization time were observed. Unlike young patients, a chance of recovery
      in elderly patients with H-H 4-5 is more difficult to achieve. Therefore, a
      conservative approach should be considered.

PMID- 21729226
TI  - Exploring effective items of physical function in slow walking speed and self
      reported mobility limitation in community-dwelling older adults.
AB  - AIM: To examine gender differences in regards to the disagreement between walking
      speed and self-reported mobility limitations, and, furthermore, to explore the
      items that affect each physical function task by comparing slow walking speed and
      self-reported mobility limitation in community-dwelling older adults. METHODS:
      The subjects consisted of 1381 community-dwelling men and women aged 65-84 years
      who were classified into four categories according to a combination of mobility
      status measured by a slow walking speed (usual gait speed < 1.0 m/s) and self
      reported mobility limitation (difficulty walking 1 km). The physical function
      tests comprised one-legged stance, tandem stance, functional reach, tandem walk,
      alternate step and five chair sit-to-stand. RESULTS: The prevalence of
      limitations increased more rapidly with age in women than in men for five
      mobility tasks (P < 0.001). The percent difference between slow walking speed and
      self-reported mobility limitation was higher in women (24%) than men (19%). The
      multivariate logistic regression model showed that after adjusting for all
      covariates, the tandem walk, alternate step and five chair sit-to-stand were
      identified as effective physical function tests in regards to mobility status as
      measured by the difference between slow walking speed and self-reported mobility
      limitation (P < 0.01). CONCLUSION: Tandem walk, alternate step and five chair sit
      to-stand are important effective items of physical function and permit good
      comparisons between slow walking speed and self-reported mobility limitation in
      community-dwelling older adults.

PMID- 21729227
TI  - Functional dissection of SiiE, a giant non-fimbrial adhesin of Salmonella
      enterica.
AB  - Salmonella enterica deploys the giant non-fimbrial adhesin SiiE to adhere to the
      apical side of polarized epithelial cells. The establishment of close contact is
      a prerequisite for subsequent invasion mediated by translocation of effector
      proteins of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type III
      secretion system (T3SS). Although SiiE is secreted into the culture medium, the
      adhesin is retained on the bacterial envelope in the phase of highest bacterial
      invasiveness. To dissect the structural requirements for secretion, retention and
      adhesive properties, comprehensive deletional and functional analyses of various
      domains of SiiE were performed. We observed that beta-sheet and coiled-coil
      domains in the N-terminal moiety of SiiE are required for the control of SiiE
      retention on the surface and co-ordinated release. These results indicate a novel
      molecular mechanism for the control of surface display of a T1SS-secreted adhesin
      that acts cooperatively with the SPI1-T3SS.

PMID- 21729228
TI  - Cytomegalovirus viraemia in the modern antiretroviral era(*).

PMID- 21729229
TI  - Viral response in stable patients switching to fosamprenavir/ritonavir
      monotherapy (the FONT Study).
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy of
      fosamprenavir/ritonavir (FPV/r) monotherapy in plasma and reservoirs in
      virologically suppressed patients. METHODS: A 48-week, prospective, single-arm
      pilot trial was carried out (trial registration: ISRCTN78584791). Patients
      receiving triple therapy [FPV/r plus two nucleoside reverse transcriptase
      inhibitors (NRTIs) for at least the previous month], with viral load (VL) <40 HIV
      1 RNA copies/mL and no previous virological failure (VF) on protease inhibitors
      (PIs), were included in the trial and received FPV/r monotherapy (700/100 mg/12
      h). VL and FPV/r levels [by liquid chromatography-tandem mass spectrometry
      (LC/MS/MS); limit of detection (LOD) 0.5 ng/mL] in cerebrospinal fluid (CSF) were
      determined at week 24. VF was defined as VL >40 copies/mL in three consecutive
      samples or >500 copies/mL in two samples. RESULTS: Enrolment was prematurely
      stopped because of a high percentage of VF. Twenty patients (45% men; median age
      43.5 years) were included in the trial. Nine patients (45%) presented therapeutic
      failure [seven (35%) had VF, and two discontinued therapy]. Resistance testing
      was available in five patients. One patient presented major PI mutations (54L,
      32I and 47V) in addition to one minor mutation (13V), whereas two patients had
      minor PI mutations (10V+36I and 71T, respectively). The patient with major PI
      mutations switched from FPV/r to darunavir/r and VL was re-suppressed. In the
      other six patients with VF, VL was re-suppressed after the reintroduction of
      NRTIs. VL was <40 copies/mL in all CSF samples (n=10). Median amprenavir plasma
      levels were 2.5 MUg/mL (range 0.7-8.6 MUg/mL) at week 24 and 2.5 MUg/mL (range
      0.4-3.8 MUg/mL) at VF. The CSF amprenavir concentration was 28.1 ng/mL (range
      6.39-83.6 ng/mL), exceeding the reported 50% inhibitory concentration (IC(50) )
      range for CSF in nine of 11 patients. CONCLUSIONS: The high percentage of
      patients with VF in our study suggests that the use of FPV/r in a simplification
      monotherapy strategy should be discouraged. Adequate amprenavir levels and
      undetectable VL in CSF were documented in all samples evaluated.

PMID- 21729230
TI  - Immunization status of children with HIV: failure to protect a vulnerable
      population.

PMID- 21729231
TI  - Will earlier diagnosis of HIV infection in late presenters reduce the frequency
      of serious opportunistic infections?

PMID- 21729233
TI  - The effects of weight loss strategies on gastric emptying and appetite control.
AB  - The gastrointestinal tract plays an important role in the improved appetite
      control and weight loss in response to bariatric surgery. Other strategies which
      similarly alter gastrointestinal responses to food intake could contribute to
      successful weight management. The aim of this review is to discuss the effects of
      surgical, pharmacological and behavioural weight loss interventions on
      gastrointestinal targets of appetite control, including gastric emptying.
      Gastrointestinal peptides are also discussed because of their integrative
      relationship in appetite control. This review shows that different strategies
      exert diverse effects and there is no consensus on the optimal strategy for
      manipulating gastric emptying to improve appetite control. Emerging evidence from
      surgical procedures (e.g. sleeve gastrectomy and Roux-en-Y gastric bypass)
      suggests a faster emptying rate and earlier delivery of nutrients to the distal
      small intestine may improve appetite control. Energy restriction slows gastric
      emptying, while the effect of exercise-induced weight loss on gastric emptying
      remains to be established. The limited evidence suggests that chronic exercise is
      associated with faster gastric emptying, which we hypothesize will impact on
      appetite control and energy balance. Understanding how behavioural weight loss
      interventions (e.g. diet and exercise) alter gastrointestinal targets of appetite
      control may be important to improve their success in weight management.

PMID- 21729234
TI  - Sensory neurone-specific receptor-mediated regulation of micturition reflex in
      urethane-anaesthetized rats.
AB  - OBJECTIVE: *  To investigate the effect of sensory neurone-specific receptors
      (SNSRs) activation on the micturition reflex in rats. MATERIALS AND METHODS: * 
      Continuous cystometrograms (CMGs, 0.04 mL/min) were performed in female Sprague
      Dawley rats under urethane anaesthesia. *  After stable micturition cycles were
      established, a selective rat SNSR1 agonist, bovine adrenal medulla 8-22 (BAM8
      22), was administered intravenously (i.v.) or intrathecally (i.t.) in normal rats
      or rats pretreated with capsaicin 4 days before the experiments. *  Micturition
      variables were recorded and compared before and after drug administration.
      RESULTS: *  Administration (i.v.) of BAM8-22 (3-100 ug/kg) significantly
      increased intercontraction intervals in a dose-dependent fashion, but did not
      affect residual urine or baseline pressure at any doses tested. *  Administration
      (i.t.) of BAM8-22 (0.01-0.3 ug) also increased intercontraction intervals in a
      dose-dependent fashion, but did not affect residual urine or baseline pressure at
      any doses tested. *  These inhibitory effects of i.v. (30 ug/kg) or i.t. (0.3 ug)
      administration of BAM8-22 still occurred after capsaicin pretreatment.
      CONCLUSIONS: *  These results indicate that in urethane-anaesthetized rats
      activation of SNSRs can inhibit the micturition reflex via pathways independent
      of capsaicin-sensitive C-fibres. *  Thus SNSRs could be a potential target for
      the treatment of bladder dysfunction, e.g. overactive bladder.

PMID- 21729235
TI  - Dose-response relationship between alcohol consumption before and during
      pregnancy and the risks of low birthweight, preterm birth and small for
      gestational age (SGA)-a systematic review and meta-analyses.
AB  - BACKGROUND: Descriptions of the effects of moderate alcohol consumption during
      pregnancy on adverse pregnancy outcomes have been inconsistent. OBJECTIVE: To
      review systematically and perform meta-analyses on the effect of maternal alcohol
      exposure on the risk of low birthweight, preterm birth and small for gestational
      age (SGA). SEARCH STRATEGY: Using Medical Subject Headings, a literature search
      of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science
      between 1 January 1980 and 1 August 2009 was performed followed by manual
      searches. SELECTION CRITERIA: Case-control or cohort studies were assessed for
      quality (STROBE), 36 available studies were included. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently extracted the information on low
      birthweight, preterm birth and SGA using a standardised protocol. Meta-analyses
      on dose-response relationships were performed using linear as well as first-order
      and second-order fractional polynomial regressions to estimate best fitting
      curves to the data. MAIN RESULTS: Compared with abstainers, the overall dose
      response relationships for low birthweight and SGA showed no effect up to 10 g
      pure alcohol/day (an average of about 1 drink/day) and preterm birth showed no
      effect up to 18 g pure alcohol/day (an average of 1.5 drinks/day); thereafter,
      the relationship showed a monotonically increasing risk for increasing maternal
      alcohol consumption. Moderate consumption during pre-pregnancy was associated
      with reduced risks for all outcomes. CONCLUSIONS: Dose-response relationship
      indicates that heavy alcohol consumption during pregnancy increases the risks of
      all three outcomes whereas light to moderate alcohol consumption shows no effect.
      Preventive measures during antenatal consultations should be initiated.

PMID- 21729236
TI  - Could the mechanisms of bariatric surgery hold the key for novel therapies?
      report from a Pennington Scientific Symposium.
AB  - Bariatric surgery is the most effective method for promoting dramatic and durable
      weight loss in morbidly obese subjects. Furthermore, type 2 diabetes is resolved
      in over 80% of patients. The mechanisms behind the amelioration in metabolic
      abnormalities are largely unknown but may be due to changes in energy metabolism,
      gut peptides and food preference. The goal of this meeting was to review the
      latest research to better understand the mechanisms behind the 'magic' of
      bariatric surgery. Replication of these effects in a non-surgical manner remains
      one of the ultimate challenges for the treatment of obesity and diabetes.
      Promising data on energy metabolism, gastrointestinal physiology, hedonic
      response and food intake were reviewed and discussed.

PMID- 21729237
TI  - Hypercoagulability in cirrhosis: causes and consequences.
AB  - Decreased levels of most coagulation factors and thrombocytopenia are the main
      haemostatic abnormalities of cirrhosis. As a consequence, this condition was,
      until recently, considered as the prototype acquired coagulopathy responsible for
      bleeding. However, recent evidence suggests that it should, rather, be regarded
      as a condition associated with normal or even increased thrombin generation. The
      bleeding events that occur in these patients should, therefore, be explained by
      the superimposed conditions that frequently occur in this setting. Due to
      elevated levels of factor VIII (procoagulant driver) in combination with
      decreased protein C (anticoagulant driver), which are typically found in patients
      with cirrhosis, a procoagulant imbalance, defined as a partial resistance to the
      in vitro anticoagulant action of thrombomodulin, can be demonstrated. Whether
      this in vitro hypercoagulability is truly representative of what occurs in vivo
      remains to be established. However, the hypothesis that it may have clinical
      consequences is attractive and deserves attention. The possible consequences that
      we discuss herein include whether (i) cirrhosis is a condition associated with
      increased risk of venous thromboembolism or portal vein thrombosis; (ii) the
      hypercoagulability associated with cirrhosis has any other role outside
      coagulation (i.e. progression of liver fibrosis); and (iii) anticoagulation
      should be used in cirrhosis. Although apparently provocative, considering
      anticoagulation as a therapeutic option in patients with cirrhosis is now
      supported by a rationale of increasing strength. There may be subgroups of
      patients who benefit from anticoagulation to treat or prevent thrombosis and to
      slow hepatic fibrosis. Clinical studies are warranted to explore these
      therapeutic options.

PMID- 21729238
TI  - Alterations in coagulation and fibrinolysis after levothyroxine exposure in
      healthy volunteers: a controlled randomized crossover study.
AB  - BACKGROUND: Several hemostatic abnormalities have been reported in
      hyperthyroidism, but the overall effect of thyroid hormone excess on coagulation
      and fibrinolysis is unclear. OBJECTIVE: Our aim was to assess whether the use of
      supraphysiological doses of levothyroxine leads to coagulation activation and
      inhibition of fibrinolysis. PATIENTS AND METHODS: Healthy volunteers were
      randomized to receive levothyroxine or no medication for 14 days with a washout
      period of at least 28 days in a crossover design. To study the effects of
      different degrees of thyroid hormone excess, 16 participants received
      levothyroxine in a dose of 0.3 mg per day, and 12 received levothyroxine 0.45 or
      0.6 mg per day depending on body weight. Several variables of coagulation and
      fibrinolysis were measured. RESULTS: Levels of von Willebrand factor activity
      (VWF:RiCo) and antigen (VWF:Ag), factor (F) VIII, plasminogen activator inhibitor
      1 (PAI-1) and clot-lysis time were slightly higher after levothyroxine 0.3 mg per
      day than after the control situation, but only levels of VWF showed a significant
      increase from baseline. After levothyroxine 0.45 or 0.6 mg per day, levels of
      fibrinogen increased by 17%, VWF activity by 24%, VWF antigen by 26%, FVIII by
      19%, FIX by 14%, FX by 7%, PAI-1 by 116% and clot-lysis time by 14%, and
      activated partial thromboplastin time decreased by 3%; all were significant
      changes compared with the control situation. We did not observe clear evidence of
      coagulation activation. CONCLUSIONS: Our data suggest that thyroid hormone excess
      increases coagulation factor levels and inhibits fibrinolysis in a dose-dependent
      fashion. This implies an increased risk of venous thrombosis during
      hyperthyroidism.

PMID- 21729239
TI  - Body weight and fat mass index as strong predictors of factor VIII in vivo
      recovery in adults with hemophilia A.
AB  - BACKGROUND: The treatment of hemophilia A requires infusions of factor VIII
      (FVIII) concentrates. The number of units to be given in order to obtain the
      target level is calculated using the formula: [body weight (BW) * desired FVIII
      increase]/2, which assumes that each unit infused per kg of BW increases the
      FVIII level by 2%. OBJECTIVES: The present observational study evaluated the
      dependence of FVIII recovery on different morphometrical variables: BW, fat mass
      index (FMI), body mass index, and the difference between actual and ideal BW.
      PATIENTS AND METHODS: FVIII recovery was measured in 46 non-actively bleeding
      hemophilia A patients, being treated with a recombinant FVIII concentrate.
      Regression trees were used to identify morphometrical predictors of recovery.
      RESULTS: The median recovery was 2.08 for all patients, 2.63 for those with a BW
      >= 81.0 kg and 1.87 for others (P < 0.001). The recovery was significantly higher
      when FMI was >= 20% compared with FMI < 15% (median recovery: 2.35 vs. 1.74; P =
      0.007). Using regression trees, three groups were created: BW < 80.5 kg and FMI <
      22.3%, BW < 80.5 kg and FMI >= 22.3% and BW >= 80.5 kg. Median recovery in these
      groups was 1.80, 2.16 and 2.63, respectively (P < 0.001). CONCLUSIONS: The dose
      calculation of FVIII should take into account both BW and FMI, and be adapted to
      underweight or overweight patients. Comparison of the average recovery after
      different FVIII concentrates should keep in mind morphometrical patient
      characteristics.

PMID- 21729240
TI  - Bleeding risk and reversal strategies for old and new anticoagulants and
      antiplatelet agents.
AB  - The most important adverse effect of antithrombotic treatment is the occurrence
      of bleeding. In the case of severe bleeding in a patient who uses anticoagulant
      agents or when a patient on anticoagulants needs to undergo an urgent invasive
      procedure, it may be useful to reverse anticoagulant treatment. Conventional
      anticoagulants such as vitamin K antagonists may be neutralized by administration
      of vitamin K or prothrombin complex concentrates, whereas heparin and heparin
      derivatives can be counteracted by protamine sulphate. The anti-hemostatic effect
      of aspirin and other antiplatelet strategies can be corrected by the
      administration of platelet concentrate and/or desmopressin, if needed. Recently,
      a new generation of anticoagulants with a greater specificity towards activated
      coagulation factors as well as new antiplatelet agents have been introduced and
      these drugs show promising results in clinical studies. A limitation of these new
      agents may be the lack of an appropriate strategy to reverse the effect if a
      bleeding event occurs, although experimental studies show hopeful results for
      some of these agents.

PMID- 21729241
TI  - Binding affinities and interactions among different heat shock element types and
      heat shock factors in rice (Oryza sativa L.).
AB  - Binding of heat shock factors (Hsfs) to heat shock elements (HSEs) leads to
      transcriptional regulation of heat shock genes. Genome-wide, 953 rice genes
      contain perfect-type, 695 genes gap-type and 1584 genes step-type HSE sequences
      in their 1-kb promoter region. The rice genome contains 13 class A, eight class B
      and four class C Hsfs (OsHsfs) and has OsHsf26 (which is of variant type) genes.
      Chemical cross-linking analysis of in vitro synthesized OsHsf polypeptides showed
      formation of homotrimers of OsHsfA2c, OsHsfA9 and OsHsfB4b proteins. Binding
      analysis of polypeptides with oligonucleotide probes containing perfect-, gap-,
      and step-type HSE sequences showed that OsHsfA2c, OsHsfA9 and OsHsfB4b
      differentially recognize various model HSEs as a function of varying reaction
      temperatures. The homomeric form of OsHsfA2c and OsHsfB4b proteins was further
      noted by the bimolecular fluorescence complementation approach in onion epidermal
      cells. In yeast two-hybrid assays, OsHsfB4b showed homomeric interaction as well
      as distinct heteromeric interactions with OsHsfA2a, OsHsfA7, OsHsfB4c and
      OsHsf26. Transactivation activity was noted in OsHsfA2c, OsHsfA2d, OsHsfA9,
      OsHsfC1a and OsHsfC1b in yeast cells. These differential patterns pertaining to
      binding with HSEs and protein-protein interactions may have a bearing on the
      cellular functioning of OsHsfs under a range of different physiological and
      environmental conditions.

PMID- 21729242
TI  - Neutralization of haemorrhagic activity of viper venoms by 1-(3
      dimethylaminopropyl)-1-(4-fluorophenyl)-3-oxo-1,3-dihydroisobenzofuran-5
      carbonitrile.
AB  - Viper envenomation undeniably induces brutal local manifestations such as
      haemorrhage, oedema and necrosis involving massive degradation of extracellular
      matrix at the bitten region and many a times results in dangerous systemic
      haemorrhage including pulmonary shock. Snake venom metalloproteases (SVMPs) are
      being considered to be the primary culprits for the venom-induced haemorrhage. As
      a consequence, the venom researchers and medical practitioners are in deliberate
      quest of SVMP inhibitors. In this study, we evaluated the inhibitory effect of 1
      (3-dimethylaminopropyl)-1-(4-fluorophenyl)-3-oxo-1,3-dihydroisobenzofuran-5
      carbonitrile (DFD) on viper venom-induced haemorrhagic and PLA(2) activities. DFD
      effectively neutralized the haemorrhagic activity of the medically important
      viper venoms such as Echis carinatus, Echis ocelatus, Echis carinatus sochureki,
      Echis carinatus leakeyi and Crotalus atrox in a dose-dependent manner. The
      histological examinations revealed that the compound DFD effectively neutralizes
      the basement membrane degradation, and accumulation of inflammatory leucocytes at
      the site of Echis carinatus venom injection further confirms the inhibition of
      haemorrhagic activity. In addition, DFD dose dependently inhibited the PLA(2)
      activities of Crotalus atrox and E. c. leakeyi venoms. According to the docking
      studies, DFD binds to hydrophobic pocket of SVMP with the ki of 19.26 * 10(-9)
      (kcal/mol) without chelating Zn(2+) in the active site. It is concluded that the
      clinically approved inhibitors of haemorrhagins could be used as a potent first
      aid agent in snakebite management. Furthermore, a high degree of structural and
      functional homology between SVMPs and their relatives, the MMPs, suggests that
      DFD analogues may find immense value in the regulation of multifactorial
      pathological conditions like inflammation, cancer and wound healing.

PMID- 21729243
TI  - Cost-effectiveness of treating first-episode psychosis: five-year follow-up
      results from an Italian early intervention programme.
AB  - AIM: Early intervention programmes are expected to result in the reduction of
      illness severity in patients with schizophrenia, and contain health-care costs by
      reducing hospital admissions and improving the social functioning of patients.
      This study aimed to investigate the cost-effectiveness of treatment in an early
      intervention programme in comparison to standard care. METHODS: Retrospective
      analysis of data prospectively recorded in an urban area (Milan, Italy). Twenty
      three patients from an early intervention programme and 23 patients from standard
      care with first-episode psychosis were evaluated on their use of services over a
      5-year period. The Health of the Nation Outcome Scale was used to measure
      clinical status. RESULTS: Significant changes with respect to initial assessment
      were recorded on the Health of the Nation Outcome Scale, with larger effect sizes
      in the early intervention programme than in the standard care group.
      Consequently, the cost-effectiveness ratio per reduced score of severity was
      lower in the early intervention programme than in standard care (? 4802 vs. ?
      9871), with an incremental cost-effectiveness ratio, or net saving of ?-1204 for
      every incremental reduced score of severity. Over time, greater recourse to
      hospital and residential facilities to obtain comparable improvement in symptoms
      resulted in a steady cost increase for the patients in standard care.
      CONCLUSIONS: Allocation of funds to specialized early intervention programmes is
      the best alternative, as it can save costs by reducing the use of hospitals and
      residential facilities, and may produce net savings of costs in the long term.

PMID- 21729244
TI  - Synergistic virulence of Porphyromonas gingivalis and Treponema denticola in a
      murine periodontitis model.
AB  - Chronic periodontitis is characterized by the destruction of the tissues
      supporting the teeth and has been associated with the presence of a subgingival
      polymicrobial biofilm containing Porphyromonas gingivalis and Treponema
      denticola. We have investigated the potential synergistic virulence of P.
      gingivalis and T. denticola using a murine experimental model of periodontitis.
      An inoculation regime of four intra-oral doses of 1 * 10(10) P. gingivalis cells
      induced significant periodontal bone loss compared with loss in sham-inoculated
      mice, whereas doses of 1 * 10(9) cells or lower did not induce bone loss.
      Inoculation with T. denticola with up to eight doses of 1 * 10(10) cells failed
      to induce bone loss in this model. However, four doses of a co-inoculum of a 1 :
      1 ratio of P. gingivalis and T. denticola at 5 * 10(8) or 1 * 10(9) total
      bacterial cells induced the same level of bone loss as four doses of 1 * 10(10)
      P. gingivalis cells. Co-inoculation induced strong P. gingivalis-specific T-cell
      proliferative and interferon-gamma-dominant cytokine responses, and induced a
      strong T. denticola-specific interferon-gamma dominant cytokine response. Only at
      the higher co-inoculum dose of 1 * 10(10) total cells was a T. denticola-specific
      T-cell proliferative response observed. These data show that P. gingivalis and T.
      denticola act synergistically to stimulate the host immune response and to induce
      alveolar bone loss in a murine experimental periodontitis model.

PMID- 21729245
TI  - In situ analysis of multispecies biofilm formation on customized titanium
      surfaces.
AB  - Many studies to identify surfaces that enhance the incorporation of dental
      implants into bone and soft-tissue have been undertaken previously. However, to
      succeed in the clinical situation, an implant surface must not support
      development of microbial biofilms with a pathogenic potential. As a first step in
      investigating this, we used two-species and three-species biofilm models with 16S
      ribosomal RNA fluorescence in situ hybridization and confocal laser scanning
      microscopy to examine the effect of surface characteristics on biofilm formation
      by species that can colonize titanium implants in vivo: Streptococcus sanguinis,
      Actinomyces naeslundii and Lactobacillus salivarius. Surfaces blasted with Al(2)
      O(3) (S(a) = 1.0-2.0 MUm) showed a seven-fold higher bacterial adhesion after 2 h
      than turned surfaces (S(a) = 0.18 MUm) whereas porous surfaces, generated by
      anodic oxidation (S(a) = 0.4 MUm), showed four-fold greater adhesion than turned
      surfaces. Hence, increased roughness promoted adhesion, most likely through
      protection of bacteria from shear forces. Chemical modification of the blasted
      and oxidized surfaces by incorporation of Ca(2+) ions reduced adhesion compared
      with the corresponding non-modified surfaces. After 14 h, biofilm growth occurred
      in the three-species model but not in the two-species consortium (containing S.
      sanguinis and A. naeslundii only). The biofilm biovolume on all surfaces was
      similar, suggesting that the influence of surface characteristics on adhesion was
      compensated for by biofilm development.

PMID- 21729246
TI  - Live/dead real-time polymerase chain reaction to assess new therapies against
      dental plaque-related pathologies.
AB  - DNA-based methodology for the identification and detection of specific bacteria
      in dental plaque offers advantages over culturing techniques. One drawback of
      current molecular techniques like real-time quantitative polymerase chain
      reaction (RT-QPCR) is that they are not able to distinguish between live or dead
      bacteria. To overcome this problem an assay was assessed to discriminate between
      viable or dead bacteria using DNA intercalating substances, propidium monoazide
      (PMA) and ethidium monoazide (EMA) in combination with RT-QPCR. The assay was
      tested on oral pathogens: Streptococcus mutans, Prevotella intermedia and
      Aggregatibacter actinomycetemcomitans. To determine the effectiveness of EMA and
      PMA, different concentrations (from 5 to 100 MUg ml(-1)) of the substances were
      added to viable or heat-killed suspensions of both organisms (ranging from 10(8)
      to 10(4) colony-forming units ml(-1)). Afterwards, PMA was tested on mixtures of
      varying ratios of viable and dead cells. After DNA extraction, RT-QPCR was
      performed using species-specific primers. Both compounds inhibited PCR
      amplification from dead cells. The EMA treatment resulted in the largest signal
      decrease but EMA also inhibited DNA amplification from viable cells. For this
      reason, PMA was selected for use in further experiments. It was shown to be
      efficient in allowing selective PCR detection of only viable cells in mixtures
      containing both viable and dead cells. The amount of amplified DNA corresponded
      to the percentage of viable cells in the sample. The developed assay will
      potentially be useful for assessing bacterial loads remaining after disinfection
      protocols without interference by non-viable bacteria.

PMID- 21729247
TI  - Aggregatibacter actinomycetemcomitans leukotoxin is post-translationally modified
      by addition of either saturated or hydroxylated fatty acyl chains.
AB  - Aggregatibacter actinomycetemcomitans, a common inhabitant of the human upper
      aerodigestive tract, produces a repeat in toxin (RTX), leukotoxin (LtxA). The
      LtxA is transcribed as a 114-kDa inactive protoxin with activation being achieved
      by attachment of short chain fatty acyl groups to internal lysine residues.
      Methyl esters of LtxA that were isolated from A. actinomycetemcomitans strains
      JP2 and HK1651 and subjected to gas chromatography/mass spectrometry contained
      palmitoyl (C16:0, 27-29%) and palmitolyl (C16:1 cis Delta9, 43-44%) fatty acyl
      groups with smaller quantities of myristic (C14:0, 14%) and stearic (C18:0, 12
      14%) fatty acids. Liquid chromatography/mass spectrometry of tryptic peptides
      from acylated and unacylated recombinant LtxA confirmed that Lys(562) and
      Lys(687) are the sites of acyl group attachment. During analysis of recombinant
      LtxA peptides, we observed peptide spectra that were not observed as part of the
      RTX acylation schemes of either Escherichia colialpha-hemolysin or Bordetella
      pertussis cyclolysin. Mass calculations of these spectra suggested that LtxA was
      also modified by the addition of monohydroxylated forms of C14 and C16 acyl
      groups. Multiple reaction monitoring mass spectrometry identified hydroxymyristic
      and hydroxypalmitic acids in wild-type LtxA methyl esters. Single or tandem
      replacement of Lys(562) and Lys(687) with Arg blocks acylation, resulting in a
      >75% decrease in cytotoxicity when compared with wild-type toxin, suggesting that
      these post-translational modifications are playing a critical role in LtxA
      mediated target cell cytotoxicity.

PMID- 21729248
TI  - Engineering plants for the phytoremediation of RDX in the presence of the co
      contaminating explosive TNT.
AB  - The explosive compounds hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6
      trinitrotoluene (TNT) are widespread environmental contaminants commonly found as
      co-pollutants on military training ranges. TNT is a toxic carcinogen which
      remains tightly bound to the soil, whereas RDX is highly mobile leaching into
      groundwater and threatening drinking water supplies. We have engineered
      Arabidopsis plants that are able to degrade RDX, whilst withstanding the
      phytotoxicity of TNT. Arabidopsis thaliana (Arabidopsis) was transformed with the
      bacterial RDX-degrading xplA, and associated reductase xplB, from Rhodococcus
      rhodochrous strain 11Y, in combination with the TNT-detoxifying nitroreductase
      (NR), nfsI, from Enterobacter cloacae. Plants expressing XplA, XplB and NR remove
      RDX from soil leachate and grow on soil contaminated with RDX and TNT at
      concentrations inhibitory to XplA-only expressing plants. This is the first study
      to demonstrate the use of transgenic plants to tackle two chemically diverse
      organic compounds at levels comparable with those found on contaminated training
      ranges, indicating that this technology is capable of remediating concentrations
      of RDX found in situ. In addition, plants expressing XplA and XplB have
      substantially less RDX available in aerial tissues for herbivory and potential
      bioaccumulation.

PMID- 21729249
TI  - Effects of hippotherapy and therapeutic horseback riding on postural control or
      balance in children with cerebral palsy: a meta-analysis.
AB  - AIM: This research review and meta-analysis presents an overview of the effects
      of hippotherapy and therapeutic horseback riding (THR) on postural control or
      balance in children with cerebral palsy (CP). METHOD: To synthesize previous
      research findings, a systematic review and meta-analysis were undertaken.
      Relevant studies were identified by systematic searches of multiple online
      databases from the inception of the database through to May 2010. Studies were
      included if they fulfilled the following criteria: (1) quantitative study design,
      (2) investigation of the effect of hippotherapy or THR on postural control or
      balance, and (3) the study group comprised children and adults with CP. The
      selected articles were rated for methodological quality. The treatment effect was
      coded as a dichotomous outcome (positive effect or no effect) and quantified by
      odds ratio (OR). The pooled treatment effect was calculated using a random
      effects model. Meta-regression of the effect size was performed against study
      covariates, including study size, publication date, and methodological quality
      score. RESULTS: From 77 identified studies, 10 met the inclusion criteria. Two
      were excluded because they did not include a comparison group. Therapy was found
      to be effective in 76 out of 84 children with CP included in the intervention
      groups. The comparison groups comprised 89 children: 50 non-disabled and 39 with
      CP. A positive effect was shown in 21 of the children with CP in the comparison
      group regardless of the activity undertaken (i.e. physiotherapy, occupational
      therapy, sitting on a barrel or in an artificial saddle). The pooled effect size
      estimate was positive (OR 25.41, 95% CI 4.35, 148.53), demonstrating a
      statistically significant effectiveness of hippotherapy or THR in children with
      CP (p<0.001). Meta-regression of study characteristics revealed no study-specific
      factors. INTERPRETATION: The eight studies found that postural control and
      balance were improved during hippotherapy and THR. Although the generalization of
      our findings may be restricted by the relatively small sample size, the results
      clearly demonstrate that riding therapy is indicated to improve postural control
      and balance in children with CP.

PMID- 21729252
TI  - Undergraduate mental health nursing education: time to shut up?

PMID- 21729253
TI  - Implementation of a major in mental health nursing in Australian universities.
AB  - The difficulty recruiting and retaining an adequate mental health nursing
      workforce is acknowledged. The major in mental health nursing has been identified
      as a strategy to promote this specialist area of practice as desirable for
      students' future careers. Measuring its success requires the collection of
      detailed data about the structure, content, and uptake of these programmes. A
      survey was specifically developed to elicit descriptive information about the
      structure and content of a major in mental health nursing programmes. Fourteen
      universities participated in this research. Eight had implemented a major, one
      intends to do so in 2011, and five had abandoned or suspended their plans for the
      major. The findings suggest considerable variation in both structure and content
      of the major in mental health nursing throughout Australia. Students are required
      to commit to and commence the programme at differing stages, and there is a
      substantial variation in the theoretical and clinical content in mental health
      undertaken as a requirement for the major. The numbers of students taking the
      major is relatively small in most universities; however, the retention rates are
      favourable. These findings provide important data for discussion about the ideal
      structure and content of a major in mental health nursing.

PMID- 21729254
TI  - Enhancing patient adherence: outcomes of medication alliance training on
      therapeutic alliance, insight, adherence, and psychopathology with mental health
      patients.
AB  - The results of interventions to enhance patient adherence to medication have been
      inconsistent. This research investigated the utility of an enhanced adherence
      training programme to ascertain its effectiveness and the possible mechanisms of
      that effect. Forty-six clinicians were trained in 'medication alliance', and data
      were collected from 51 patients matched to the clinician. Data on clinician
      changes in skills, knowledge, and attitudes, in relation to enhancing patient
      adherence and patient changes in adherence, insight, and psychopathology were
      collected at baseline and at 6 and 12 months. The quality of the therapeutic
      relationship between the clinician and the patient was also assessed. The results
      indicated significant improvements in both clinician and patient measures, the
      majority of which were maintained over time. The quality of the therapeutic
      relationship was also enhanced. A hypothesized explanatory model accounting for
      the data was supported. It was concluded that clinician training to support
      improved patient adherence should include strategies that also enhance the
      therapeutic alliance.

PMID- 21729255
TI  - Sarcoid reaction associated with Merkel cell carcinoma revealed by
      fluorodeoxyglucose positron emission tomography: a case report.

PMID- 21729256
TI  - RASOnD-a comprehensive resource and search tool for RAS superfamily oncogenes
      from various species.
AB  - BACKGROUND: The Ras superfamily plays an important role in the control of cell
      signalling and division. Mutations in the Ras genes convert them into active
      oncogenes. The Ras oncogenes form a major thrust of global cancer research as
      they are involved in the development and progression of tumors. This has resulted
      in the exponential growth of data on Ras superfamily across different public
      databases and in literature. However, no dedicated public resource is currently
      available for data mining and analysis on this family. The present database was
      developed to facilitate straightforward accession, retrieval and analysis of
      information available on Ras oncogenes from one particular site. DESCRIPTION: We
      have developed the RAS Oncogene Database (RASOnD) as a comprehensive
      knowledgebase that provides integrated and curated information on a single
      platform for oncogenes of Ras superfamily. RASOnD encompasses exhaustive genomics
      and proteomics data existing across diverse publicly accessible databases. This
      resource presently includes overall 199,046 entries from 101 different species.
      It provides a search tool to generate information about their nucleotide and
      amino acid sequences, single nucleotide polymorphisms, chromosome positions,
      orthologies, motifs, structures, related pathways and associated diseases. We
      have implemented a number of user-friendly search interfaces and sequence
      analysis tools. At present the user can (i) browse the data (ii) search any field
      through a simple or advance search interface and (iii) perform a BLAST search and
      subsequently CLUSTALW multiple sequence alignment by selecting sequences of Ras
      oncogenes. The Generic gene browser, GBrowse, JMOL for structural visualization
      and TREEVIEW for phylograms have been integrated for clear perception of
      retrieved data. External links to related databases have been included in RASOnD.
      CONCLUSIONS: This database is a resource and search tool dedicated to Ras
      oncogenes. It has utility to cancer biologists and cell molecular biologists as
      it is a ready source for research, identification and elucidation of the role of
      these oncogenes. The data generated can be used for understanding the
      relationship between the Ras oncogenes and their association with cancer. The
      database updated monthly is freely accessible online at
      http://202.141.47.181/rasond/ and http://www.aiims.edu/RAS.html.

PMID- 21729257
TI  - Transient and steady-state auditory gamma-band responses in first-degree
      relatives of people with autism spectrum disorder.
AB  - BACKGROUND: Stimulus-related gamma-band oscillations, which may be related to
      perceptual binding, are reduced in people with autism spectrum disorders (ASD).
      The purpose of this study was to examine auditory transient and steady-state
      gamma-band findings in first-degree relatives of people with ASD to assess the
      potential familiality of these findings in ASD. METHODS: Magnetoencephalography
      (MEG) recordings in 21 parents who had a child with an autism spectrum disorder
      (pASD) and 20 healthy adult control subjects (HC) were obtained. Gamma-band phase
      locking factor (PLF), and evoked and induced power to 32, 40 and 48 Hz amplitude
      modulated sounds were measured for transient and steady-state responses.
      Participants were also tested on a number of behavioral and cognitive assessments
      related to the broad autism phenotype (BAP). RESULTS: Reliable group differences
      were seen primarily for steady-state responses. In the left hemisphere, pASD
      subjects exhibited lower phase-locked steady-state power in all three conditions.
      Total gamma-band power, including the non-phase-locked component, was also
      reduced in the pASD group. In addition, pASD subjects had significantly lower PLF
      than the HC group. Correlations were seen between MEG measures and BAP measures.
      CONCLUSIONS: The reduction in steady-state gamma-band responses in the pASD group
      is consistent with previous results for children with ASD. Steady-state responses
      may be more sensitive than transient responses to phase-locking errors in ASD.
      Together with the lower PLF and phase-locked power in first-degree relatives,
      correlations between gamma-band measures and behavioral measures relevant to the
      BAP highlight the potential of gamma-band deficits as a potential new autism
      endophenotype.

PMID- 21729258
TI  - Surgical and anesthetic considerations of laryngeal saccular cyst: a case report.
AB  - INTRODUCTION: Supraglottic laryngeal cysts are benign, uncommon lesions that have
      the potential to cause airway compromise. CASE PRESENTATION: We present a case of
      a 46-year-old Caucasian woman who was scheduled for excision of a large neck
      growth (saccular cyst) and was managed successfully. There was thorough
      consideration regarding anesthetic and surgical management. Steps taken led to a
      successful excision with no recurrence during follow up. CONCLUSION: This case
      was an opportunity to consider the challenges in the airway management associated
      with such cysts and provided reassurance that excision of these cysts is
      associated with a good post-operative outcome.

PMID- 21729259
TI  - Pituitary apoplexy following shoulder arthroplasty: a case report.
AB  - INTRODUCTION: Pituitary apoplexy following a major surgical procedure is a
      catastrophic event and the diagnosis can be delayed in a previously asymptomatic
      patient. The decision on thromboprophylaxis in shoulder replacements in the
      absence of definite guidelines, rests on a careful clinical judgment. CASE
      PRESENTATION: A previously healthy 62-year-old Caucasian male patient who
      underwent shoulder arthroplasty developed hyponatremia resistant to correction
      with saline replacement. The patient had a positive family history of deep vein
      thrombosis and pulmonary embolism and heparin thromboprophylaxis was considered
      on clinical grounds. The patient developed hyponatremia resistant to conventional
      treatment and later developed ocular localizing signs with oculomotor nerve
      palsy. The diagnosis was delayed due to other confounding factors in the
      immediate post-operative period. Subsequent workup confirmed a pituitary adenoma
      with features of pituitary insufficiency. The patient was managed successfully on
      conservative lines with a multidisciplinary approach. CONCLUSIONS: A high index
      of suspicion is required in the presence of isolated post-operative hyponatremia
      resistant to medical correction. A central cause, in particular pituitary
      adenoma, should be suspected early. Thromboprophylaxis in shoulder replacements
      needs careful consideration as it may be a contributory factor in precipitating
      this life-threatening condition.

PMID- 21729260
TI  - Fibrinogen-related proteins in ixodid ticks.
AB  - BACKGROUND: Fibrinogen-related proteins with lectin activity are believed to be
      part of the tick innate immune system. Several fibrinogen-related proteins have
      been described and characterised mainly on the basis of their cDNA sequences
      while direct biochemical evidence is missing. One of them, the haemolymph lectin
      Dorin M from the tick Ornithodoros moubata was isolated and characterised in more
      depth. RESULTS: Several fibrinogen-related proteins were detected in the
      haemolymph of ixodid ticks Dermacentor marginatus, Rhipicephalus appendiculatus,
      R. pulchellus, and R. sanguineus. These proteins were recognised by sera directed
      against the tick lectin Dorin M and the haemagglutination activity of the ticks
      R. appendiculatus and D. marginatus. Cross-reactivity of the identified proteins
      with antibodies against the fibrinogen domain of the human ficolin was also
      shown. The carbohydrate-binding ability of tick haemolymph was confirmed by
      haemagglutination activity assays, and this activity was shown to be inhibited by
      neuraminic acid and sialylated glycoproteins as well as by N-acetylated
      hexosamines. The fibrinogen-related proteins were shown to be glycosylated and
      they were localised in salivary glands, midguts, and haemocytes of D. marginatus.
      Hemelipoglycoprotein was also recognised by sera directed against the fibrinogen
      related proteins in all three Rhipicephalus species as well as in D. marginatus.
      However, this protein does not contain the fibrinogen domain and thus, the
      binding possibly results from the structure similarity between
      hemelipoglycoprotein and the fibrinogen domain. CONCLUSIONS: The presence of
      fibrinogen-related proteins was shown in the haemolymph of four tick species in
      high abundance. Reactivity of antibodies directed against ficolin or fibrinogen
      related proteins with proteins which do not contain the fibrinogen domain points
      out the importance of sequence analysis of the identified proteins in further
      studies. Previously observed expression of fibrinogen-related proteins in
      haemocytes together with the results of this study suggest involvement of
      fibrinogen-related proteins in tick immunity processes. Thus, they have potential
      as targets for anti-tick vaccines and as antimicrobial proteins in pharmacology.
      Research on fibrinogen-related proteins could reveal further details of tick
      innate immunity processes.

PMID- 21729261
TI  - Chromosome 3q29 deletion with gastrointestinal malformation: a case report.
AB  - INTRODUCTION: Most chromosome 3 deletions are associated with neuro-developmental
      and eye abnormalities. Here, we report a rare and unusual multiple congenital
      abnormality, including ano-rectal malformation, in conjunction with chromosome
      3q29 segment deletion, which has not previously been reported. CASE PRESENTATION:
      A three-month-old female Jordanian baby presented with an absent anus and corneal
      opacities and was referred for further management after a diverting colostomy
      operation at the age of one day. CONCLUSION: Chromosome 3q29 deletion is
      associated with additional abnormalities to neurological ones, such as ano-rectal
      malformations. We need to investigate a patient fully to find such hidden
      clinical features.

PMID- 21729262
TI  - Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of
      two oral formulations of mesalazine.
AB  - BACKGROUND: The treatment of ulcerative colitis (UC) can place a substantial
      financial burden on healthcare systems. The anti-inflammatory compound 5
      aminosalicylic acid (5-ASA; mesalazine) is the recommended first-line treatment
      for patients with UC. In this analysis, the incremental cost effectiveness ratio
      (ICER) of two oral formulations of 5-ASA (Mezavant(r) and Asacol(r)) is examined
      in the treatment of patients with mild-to-moderate, active UC in Germany.
      METHODS: A Markov cohort model was developed to assess the cost effectiveness of
      Mezavant compared with Asacol over a 5-year period in the German Statutory Health
      Insurance (SHI). Drug pricing details for 2009 were applied throughout the model,
      and overall resource use was determined and also fitted to 2009 from published
      results of a large cross sectional study of German SHI patients. Cost per quality
      adjusted life year (QALY) was the primary endpoint for this study. Remission
      rates were obtained using data from a randomised, phase III trial of Mezavant
      with an active Asacol reference arm and a long-term, open label, safety and
      tolerability trial of Mezavant. Uncertainty in the study model was assessed using
      one-way and probabilistic sensitivity analyses applying a Monte Carlo simulation.
      RESULTS: Over a 5-year period, healthcare costs for patients receiving Mezavant
      were 624 Euro lower than for patients receiving Asacol. Additionally, patients
      receiving Mezavant gained 0.011 QALYs or 18 more days in remission compared with
      Asacol. One-way sensitivity analyses suggest that these results are driven by
      both differences in the acquisition cost between mesalazine formulations and
      differences in treatment efficacy. Furthermore, sensitivity analyses suggest a
      probability of 76% for cost savings and higher QALYs with Mezavant compared with
      Asacol. If adherence and its influence on the remission rates and the risk of
      developing colorectal cancer were included in the model, the results might have
      even been more favorable to Mezavant due to its once daily dosing regimen.
      CONCLUSIONS: This model suggests that patients treated with Mezavant may achieve
      increased time in remission and higher QALYs, with lower direct costs to the SHI
      when compared with Asacol. Mezavant may therefore be a suitable first-line option
      for the induction and maintenance of remission in UC.

PMID- 21729263
TI  - Octreotide-induced thrombocytopenia: a case report.
AB  - INTRODUCTION: Thrombocytopenia is an extremely rare complication of octreotide
      therapy and can be life threatening in the setting of esophageal variceal
      bleeding. We report a case of octreotide-induced reversible thrombocytopenia in a
      54-year-old Caucasian man with alcohol-induced cirrhosis and upper
      gastrointestinal bleeding. CASE PRESENTATION: Our patient's platelet count
      dropped from 155,000/mm3 upon admission to 77,000/mm3 a few hours after
      initiation of octreotide therapy and stayed low until the drug's administration
      was discontinued. Significant recovery was achieved quickly after discontinuation
      of octreotide. CONCLUSIONS: Thrombocytopenia is a rare but potentially serious
      side effect of octreotide therapy and may complicate esophageal variceal
      bleeding. Physicians should be vigilant in identifying this potentially serious
      condition.

PMID- 21729264
TI  - Numerical simulation of strain-adaptive bone remodelling in the ankle joint.
AB  - BACKGROUND: The use of artificial endoprostheses has become a routine procedure
      for knee and hip joints while ankle arthritis has traditionally been treated by
      means of arthrodesis. Due to its advantages, the implantation of endoprostheses
      is constantly increasing. While finite element analyses (FEA) of strain-adaptive
      bone remodelling have been carried out for the hip joint in previous studies, to
      our knowledge there are no investigations that have considered remodelling
      processes of the ankle joint. In order to evaluate and optimise new generation
      implants of the ankle joint, as well as to gain additional knowledge regarding
      the biomechanics, strain-adaptive bone remodelling has been calculated separately
      for the tibia and the talus after providing them with an implant. METHODS: FE
      models of the bone-implant assembly for both the tibia and the talus have been
      developed. Bone characteristics such as the density distribution have been
      applied corresponding to CT scans. A force of 5,200 N, which corresponds to the
      compression force during normal walking of a person with a weight of 100 kg
      according to Stauffer et al., has been used in the simulation. The bone
      adaptation law, previously developed by our research team, has been used for the
      calculation of the remodelling processes. RESULTS: A total bone mass loss of 2%
      in the tibia and 13% in the talus was calculated. The greater decline of density
      in the talus is due to its smaller size compared to the relatively large implant
      dimensions causing remodelling processes in the whole bone tissue. In the tibia,
      bone remodelling processes are only calculated in areas adjacent to the implant.
      Thus, a smaller bone mass loss than in the talus can be expected. There is a high
      agreement between the simulation results in the distal tibia and the literature
      regarding. CONCLUSIONS: In this study, strain-adaptive bone remodelling processes
      are simulated using the FE method. The results contribute to a better
      understanding of the biomechanical behaviour of the ankle joint and hence are
      useful for the optimisation of the implant geometry in the future.

PMID- 21729265
TI  - The effectiveness of case management for comorbid diabetes type 2 patients; the
      CasCo study. Design of a randomized controlled trial.
AB  - BACKGROUND: More than half of the patients with type 2 diabetes (T2DM) patients
      are diagnosed with one or more comorbid disorders. They can participate in
      several single-disease oriented disease management programs, which may lead to
      fragmented care because these programs are not well prepared for coordinating
      care between programs. Comorbid patients are therefore at risk for suboptimal
      treatment, unsafe care, inefficient use of health care services and unnecessary
      costs. Case management is a possible model to counteract fragmented care for
      comorbid patients. It includes evidence-based optimal care, but is tailored to
      the individual patients' preferences.The objective of this study is to examine
      the effectiveness of a case management program, in addition to a diabetes
      management program, on the quality of care for comorbid T2DM patients.
      METHODS/DESIGN: The study is a randomized controlled trial among patients with
      T2DM and at least one comorbid chronic disease (N=230), who already participate
      in a diabetes management program. Randomization will take place at the level of
      the patients in general practices. Trained practice nurses (case managers) will
      apply a case management program in addition to the diabetes management program.
      The case management intervention is based on the Guided Care model and includes
      six elements; assessing health care needs, planning care, create access to other
      care providers and community resources, monitoring, coordinating care and
      recording of all relevant information. Patients in the control group will
      continue their participation in the diabetes management program and receive care
      as-usual from their general practitioner and other care providers. DISCUSSION: We
      expect that the case management program, which includes better structured care
      based on scientific evidence and adjusted to the patients' needs and priorities,
      will improve the quality of care coordination from both the patients' and
      caregivers' perspective and will result in less consumption of health care
      services. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1847.

PMID- 21729266
TI  - Antibiotic use for upper respiratory tract infections in children: a cross
      sectional survey of knowledge, attitudes, and practices (KAP) of parents in
      Greece.
AB  - BACKGROUND: Upper respiratory tract infections (URTIs) are common in children.
      The cause of URTIs is usually viral, but parents' attitudes often contribute to
      inappropriate prescription of antibiotics, promoting antibiotic resistance. The
      objective of this study was to document and analyse parental beliefs on
      antibiotic use for children with URTIs in Greece, a country with high levels of
      antibiotic use and antibiotic resistance. METHODS: A knowledge-attitude-practice
      questionnaire was developed and distributed to Greek parents caring for children
      who were 5-6 years old, between January and July of the same school year. The
      sample of the study contained parents from all geographic areas of Greece.
      RESULTS: The majority of Greek parents (80%) believed that UTRIs are mostly self
      limited, although 74% of them expected to receive antibiotics when such a
      diagnosis was given. Earache was the most common reason for which parents
      expected antibiotics (45%). Greek parents rarely gave antibiotics to their
      children without medical advice (10%) and most (88%) believed that unnecessary
      antibiotic use drives antibiotic resistance and they were happy to receive
      symptomatic therapy if instructed by their physician. Almost 70% of parents
      confused antibiotics with other medicines used for symptomatic therapy for a
      child with URTI. CONCLUSION: Greek parents have a trusted relationship with their
      paediatrician and rarely give antibiotics without medical advice, indicating that
      parents contribute less than expected to antibiotic misuse. Parents also
      appreciate the benign course of most URTIs and the fact that unnecessary
      antibiotic use is harmful. More time needs to be invested in educating mostly
      physicians on the potential benefit from reducing antibiotic prescribing for
      children with URTI.

PMID- 21729267
TI  - Identification of lignin genes and regulatory sequences involved in secondary
      cell wall formation in Acacia auriculiformis and Acacia mangium via de novo
      transcriptome sequencing.
AB  - BACKGROUND: Acacia auriculiformis * Acacia mangium hybrids are commercially
      important trees for the timber and pulp industry in Southeast Asia. Increasing
      pulp yield while reducing pulping costs are major objectives of tree breeding
      programs. The general monolignol biosynthesis and secondary cell wall formation
      pathways are well-characterized but genes in these pathways are poorly
      characterized in Acacia hybrids. RNA-seq on short-read platforms is a rapid
      approach for obtaining comprehensive transcriptomic data and to discover
      informative sequence variants. RESULTS: We sequenced transcriptomes of A.
      auriculiformis and A. mangium from non-normalized cDNA libraries synthesized from
      pooled young stem and inner bark tissues using paired-end libraries and a single
      lane of an Illumina GAII machine. De novo assembly produced a total of 42,217 and
      35,759 contigs with an average length of 496 bp and 498 bp for A. auriculiformis
      and A. mangium respectively. The assemblies of A. auriculiformis and A. mangium
      had a total length of 21,022,649 bp and 17,838,260 bp, respectively, with the
      largest contig 15,262 bp long. We detected all ten monolignol biosynthetic genes
      using Blastx and further analysis revealed 18 lignin isoforms for each species.
      We also identified five contigs homologous to R2R3-MYB proteins in other plant
      species that are involved in transcriptional regulation of secondary cell wall
      formation and lignin deposition. We searched the contigs against public microRNA
      database and predicted the stem-loop structures of six highly conserved microRNA
      families (miR319, miR396, miR160, miR172, miR162 and miR168) and one legume
      specific family (miR2086). Three microRNA target genes were predicted to be
      involved in wood formation and flavonoid biosynthesis. By using the assemblies as
      a reference, we discovered 16,648 and 9,335 high quality putative Single
      Nucleotide Polymorphisms (SNPs) in the transcriptomes of A. auriculiformis and A.
      mangium, respectively, thus yielding useful markers for population genetics
      studies and marker-assisted selection. CONCLUSION: We have produced the first
      comprehensive transcriptome-wide analysis in A. auriculiformis and A. mangium
      using de novo assembly techniques. Our high quality and comprehensive assemblies
      allowed the identification of many genes in the lignin biosynthesis and secondary
      cell wall formation in Acacia hybrids. Our results demonstrated that Next
      Generation Sequencing is a cost-effective method for gene discovery,
      identification of regulatory sequences, and informative markers in a non-model
      plant.

PMID- 21729268
TI  - Cardiovascular risk factor treatment targets and renal complications in high risk
      vascular patients: a cohort study.
AB  - BACKGROUND: To determine if recommended treatment targets, as specified in
      clinical practice guidelines for the management of cardiovascular disease,
      reduces the risk of renal complications in high risk patient populations.
      METHODS: This was a cohort study. Participants in Utrecht, The Netherlands either
      at risk of, or had cardiovascular disease were recruited. Cardiovascular
      treatment targets were achievement of control in systolic and diastolic blood
      pressure, total and low-density cholesterol, and treatment of albuminuria.
      Outcome measures were time to development of end stage renal failure or
      symptomatic renal atherosclerotic disease requiring intervention. RESULTS: The
      cohort consisted of 7,208 participants; 1,759 diabetics and 4,859 with clinically
      manifest vascular disease. The median age was 57 years and 67% were male.
      Overall, 29% of the cohort achieved the treatment target for systolic blood
      pressure, 39% for diastolic blood pressure, 28% for total cholesterol, 31% for
      LDL cholesterol and 78% for albuminuria. The incidence rate for end stage renal
      failure and renal atherosclerotic disease reduced linearly with each additional
      treatment target achieved (p value less than 0.001). Achievement of any two
      treatment targets reduced the risk of renal complications, hazard ratio 0.46 (95%
      CI 0.26-0.82). For patients with clinically manifest vascular disease and
      diabetes, the hazard ratios were 0.56 (95% CI 0.28 - 1.12) and 0.28 (95%CI 0.10 -
      0.79) respectively. CONCLUSION: Clinical guidelines for cardiovascular disease
      management do reduce risk of renal complications in high risk patients. Benefits
      are seen with attainment of any two treatment targets.

PMID- 21729269
TI  - Predation efficiency of Anopheles gambiae larvae by aquatic predators in western
      Kenya highlands.
AB  - BACKGROUND: The current status of insecticide resistance in mosquitoes and the
      effects of insecticides on non-target insect species have raised the need for
      alternative control methods for malaria vectors. Predation has been suggested as
      one of the important regulation mechanisms for malaria vectors in long-lasting
      aquatic habitats, but the predation efficiency of the potential predators is
      largely unknown in the highlands of western Kenya. In the current study, we
      examined the predation efficiency of five predators on Anopheles gambiae s.s
      larvae in 24 hour and semi- field evaluations. METHODS: Predators were collected
      from natural habitats and starved for 12 hours prior to starting experiments.
      Preliminary experiments were conducted to ascertain the larval stage most
      predated by each predator species. When each larval instar was subjected to
      predation, third instar larvae were predated at the highest rate. Third instar
      larvae of An. gambiae were introduced into artificial habitats with and without
      refugia at various larval densities. The numbers of surviving larvae were counted
      after 24 hours in 24. In semi-field experiments, the larvae were counted daily
      until they were all either consumed or had developed to the pupal stage.
      Polymerase chain reaction was used to confirm the presence of An. gambiae DNA in
      predator guts. RESULTS: Experiments found that habitat type (P < 0.0001) and
      predator species (P < 0.0001) had a significant impact on the predation rate in
      the 24 hour evaluations. In semi-field experiments, predator species (P < 0.0001)
      and habitat type (P < 0.0001) were significant factors in both the daily survival
      and the overall developmental time of larvae. Pupation rates took significantly
      longer in habitats with refugia. An. gambiae DNA was found in at least three out
      of ten midguts for all predator species. Gambusia affins was the most efficient,
      being three times more efficient than tadpoles. CONCLUSION: These experiments
      provide insight into the efficiency of specific natural predators against
      mosquito larvae. These naturally occurring predators may be useful in biocontrol
      strategies for aquatic stage An. gambiae mosquitoes. Further investigations
      should be done in complex natural habitats for these predators.

PMID- 21729270
TI  - An efficient approach to finding Siraitia grosvenorii triterpene biosynthetic
      genes by RNA-seq and digital gene expression analysis.
AB  - BACKGROUND: Siraitia grosvenorii (Luohanguo) is an herbaceous perennial plant
      native to southern China and most prevalent in Guilin city. Its fruit contains a
      sweet, fleshy, edible pulp that is widely used in traditional Chinese medicine.
      The major bioactive constituents in the fruit extract are the cucurbitane-type
      triterpene saponins known as mogrosides. Among them, mogroside V is nearly 300
      times sweeter than sucrose. However, little is known about mogrosides
      biosynthesis in S. grosvenorii, especially the late steps of the pathway.
      RESULTS: In this study, a cDNA library generated from of equal amount of RNA
      taken from S. grosvenorii fruit at 50 days after flowering (DAF) and 70 DAF were
      sequenced using Illumina/Solexa platform. More than 48,755,516 high-quality reads
      from a cDNA library were generated that was assembled into 43,891 unigenes. De
      novo assembly and gap-filling generated 43,891 unigenes with an average sequence
      length of 668 base pairs. A total of 26,308 (59.9%) unique sequences were
      annotated and 11,476 of the unique sequences were assigned to specific metabolic
      pathways by the Kyoto Encyclopedia of Genes and Genomes. cDNA sequences for all
      of the known enzymes involved in mogrosides backbone synthesis were identified
      from our library. Additionally, a total of eighty-five cytochrome P450 (CYP450)
      and ninety UDP-glucosyltransferase (UDPG) unigenes were identified, some of which
      appear to encode enzymes responsible for the conversion of the mogroside backbone
      into the various mogrosides. Digital gene expression profile (DGE) analysis using
      Solexa sequencing was performed on three important stages of fruit development,
      and based on their expression pattern, seven CYP450s and five UDPGs were selected
      as the candidates most likely to be involved in mogrosides biosynthesis.
      CONCLUSION: A combination of RNA-seq and DGE analysis based on the next
      generation sequencing technology was shown to be a powerful method for
      identifying candidate genes encoding enzymes responsible for the biosynthesis of
      novel secondary metabolites in a non-model plant. Seven CYP450s and five UDPGs
      were selected as potential candidates involved in mogrosides biosynthesis. The
      transcriptome data from this study provides an important resource for
      understanding the formation of major bioactive constituents in the fruit extract
      from S. grosvenorii.

PMID- 21729271
TI  - Phenotypic and genotypic characterization of Stenotrophomonas maltophilia
      isolates from patients with cystic fibrosis: genome diversity, biofilm formation,
      and virulence.
AB  - BACKGROUND: Stenotrophomonas maltophilia is emerging as one of the most
      frequently found bacteria in cystic fibrosis (CF) patients. In the present study,
      phenotypic and genotypic traits of a set of 98 isolates of S. maltophilia
      obtained from clinical (CF and non-CF patients) and environmental sources were
      comparatively evaluated. RESULTS: S. maltophilia exhibited a high level of
      genomic diversity in both CF and non-CF group, thus possibly allowing this
      bacterium to expand its pathogenic potentials. Strains sharing the same pulsotype
      infected different patients, thus likely indicating the occurrence of clonal
      spread or acquisition by a common source. CF isolates differed greatly in some
      phenotypic traits among each other and also when compared with non-CF isolates,
      demonstrating increased mean generation time and susceptibility to oxidative
      stress, but reduced ability in forming biofilm. Furthermore, in CF isolates
      flagella- and type IV pili-based motilities were critical for biofilm
      development, although not required for its initiation. Sequential isogenic
      strains isolated from the same CF patient displayed heterogeneity in biofilm and
      other phenotypic traits during the course of chronic infection. CF and non-CF
      isolates showed comparable virulence in a mouse model of lung infection.
      CONCLUSIONS: Overall, the phenotypic differences observed between CF and non-CF
      isolates may imply different selective conditions and persistence (adaptation)
      mechanisms in a hostile and heterogeneous environment such as CF lung. Molecular
      elucidation of these mechanisms will be essential to better understand the
      selective adaptation in CF airways in order to design improved strategies useful
      to counteract and eradicate S. maltophilia infection.

PMID- 21729272
TI  - Simultaneous clinical resolution of focal segmental glomerulosclerosis associated
      with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and
      rituximab.
AB  - BACKGROUND: Although renal involvement in advanced haematological malignancies is
      common, glomerulonephritis associated with lymphoproliferative disorders is rare,
      and the related pathogenetic mechanisms are still poorly understood. We present a
      rare case of chronic lymphocytic leukaemia(CLL)-associated focal segmental
      glomerulosclerosis with nephrotic-range proteinuria. CASE PRESENTATION: A 53-year
      old Caucasian man, previously healthy, with no history of hypertension, alcohol
      use or smoking presented with rapid weight gain, massive peripheral oedema, and
      hypertension. Laboratory findings included a white blood cell count of 49,800
      cells/mm3 with an absolute lymphocyte count of 47,000 cells/mm3, serum albumin of
      2.3 g/dL, urea 65 mg/dL, and creatinine 1.5 mg/dL. A 24-hour urine collection
      contained 7.1 g protein and significant haematuria. A peripheral blood smear
      showed mature lymphocytosis and smudge cells. Diagnostic imaging showed mild
      paraaortic lymphadenopathy with no renal abnormalities. Bone marrow aspiration
      and trephine biopsy showed diffuse and focal infiltration with B-CLL lymphocytes.
      Percutaneous renal biopsy revealed total sclerosis in 3/21(14%) of the glomeruli
      and focal and segmental solidification and sclerosis in 4/21 (19%) glomeruli. A
      regimen of fludarabine, cyclophosphamide and rituximab was successful in inducing
      remission of the CLL and clinical resolution of the nephritic-range proteinuria.
      CONCLUSIONS: A multidisciplinary approach to monitor both the malignancy and the
      glomerular lesions is crucial for the optimal management of paraneoplastic
      glomerulonephritis. Although chemotherapy with fludarabine, cyclophosphamide and
      rituximab successfully treated CLL-associated nephrotic syndrome in our patient,
      further studies are required to confirm efficacy in this setting.

PMID- 21729273
TI  - Underage drinking on saturday nights, sociodemographic and environmental risk
      factors: a cross-sectional study.
AB  - BACKGROUND: Excessive alcohol consumption in underage people is a rising
      phenomenon. A major proportion of the disease burden and deaths of young people
      in developed nations is attributable to alcohol abuse. The aim of this study was
      to investigate social, demographic and environmental factors that may raise the
      risk of Saturday night drinking and binge drinking among Italian school students.
      METHODS: The study was conducted on a sample of 845 Italian underage school
      students, by means of an anonymous, self-test questionnaire. Multivariate
      logistic regression was applied to identify independent risk factors for alcohol
      drinking and binge drinking. Ordered logistic regression was used to identify
      independent risk factors for harmful drinking patterns. RESULTS: The independent
      variables that confer a higher risk of drinking in underage students are older
      age classes, male sex, returning home after midnight, belonging to a group with
      little respect for the rules, or to a group where young people are not seen as
      leaders. The higher the perception of alcohol consumption by the group, the
      higher the risk. Spending time in bars or discos coincides with a two-fold or
      four-fold increase, respectively, in the risk of alcohol consumption. CONCLUSION:
      Our findings show that certain environmental and social risk factors are
      associated with underage drinking. The most important role for preventing young
      people's exposure to these factors lies with the family, because only parents can
      exert the necessary control and provide a barrier against potentially harmful
      situations.

PMID- 21729274
TI  - An easy intervention to improve short-term adherence to medications in community
      dwelling older outpatients. A pilot non-randomised controlled trial.
AB  - BACKGROUND: Complex interventions to improve compliance to pharmacological
      treatment in older people have given mixed results and are not easily applicable
      in clinical practice. The aim of this study was to test the short-term efficacy
      on self-reported medication adherence of an easy intervention in which the
      patient or caregiver was asked to transcribe the pharmacological treatment while
      it was dictated to him/her by the doctor. METHODS: Pilot non-randomised
      controlled trial involving 108 community-dwelling outpatients aged 65+ (54 in the
      intervention arm, 54 controls) referred to a geriatric service from May to July
      2009 and prescribed by the geriatrician a change in therapy. The intervention was
      applied at the end of the visit to the person managing the medications, be it the
      elder or his/her caregiver. Outcome of the study was the occurrence of any
      adherence error, assessed at a one-month follow-up by means of a semi-structured
      interview. RESULTS: The socio-demographic, functional and clinical
      characteristics of the two compared groups were similar at baseline. At a one
      month follow-up 43 subjects (40%) had made at least one adherence error, whether
      unintentional or intentional. In the intervention group the prevalence of
      adherence errors was lower than in controls (20% vs 59%; adjusted odds ratio
      0.16, 95% confidence interval 0.07 - 0.39; p < 0.001) after adjusting for the
      person managing the medications, the adherence errors at baseline and for the
      number of prescribed drugs. CONCLUSIONS: In an older outpatient population the
      intervention considered was effective in reducing the prevalence of adherence
      errors in the month following the visit. TRIAL REGISTRATION: Australian and New
      Zealand Clinical Trials Register (ANZCTR): ACTRN12611000347965.

PMID- 21729275
TI  - Low Mannose-Binding Lectin (MBL) genotype is associated with future
      cardiovascular events in type 2 diabetic South Asians. A prospective cohort
      study.
AB  - BACKGROUND: South Asians have a high burden of type 2 diabetes and vascular
      complications. Vascular inflammation is considered central in the pathophysiology
      of atherosclerosis, and the complement system is thought to play an important
      role. Mannose-Binding Lectin (MBL), which activates the lectin pathway of
      complement activation, has been introduced as a risk marker of vascular damage.
      The present study explores the association of MBL levels, genotype and
      cardiovascular events in type 2 diabetic South Asians. METHODS: We conducted a
      prospective observational study. A cohort consisting of 168 type 2 diabetic South
      Asians was followed for a median duration of 7.66 years. At baseline, MBL levels
      and genotype were determined. The association with future cardiovascular events
      was assessed by Cox proportional hazard regression. RESULTS: During follow-up, 31
      cardiovascular events occurred in 22 subjects (11 men, 11 women). The O/O
      genotype was significantly associated with the occurrence of cardiovascular
      events (hazard ratio 3.42, 95%CI 1.24-9.49, P = 0.018). However, log MBL levels
      were not associated with the occurrence of cardiovascular events (hazard ratio
      0.93, 95% CI 0.50-1.73). CONCLUSIONS: In type 2 diabetic South Asians, the O/O
      MBL genotype is associated with cardiovascular events, although single serum MBL
      levels are not.

PMID- 21729276
TI  - Odontogenic tumors and giant cell lesions of jaws--a nine year study.
AB  - OBJECTIVES: A definite geographic variation has been observed in the frequency of
      odontogenic tumors and giant cell lesions of the jaws reported from different
      parts of the world. However, there are a few studies on these lesions, especially
      giant cell lesions, reported from India. Hence, this study was designed to
      provide a demographic data on the odontogenic tumors and giant cell lesions
      reported from our institute located in the city of Hyderabad. Hyderabad is the
      capital city of the southern state of Andhra Pradesh in India. A retrospective
      analysis of odontogenic tumors and giant cell lesions of jaws reported in our
      institute between the years 2000 and 2009 was done and this data was compared
      with previous reports from different parts of the world and India. METHODS:
      Biopsies of the lesions received between the years 2000 and 2009 were reviewed
      and patient's history, clinical, radiological and histopathological
      characteristics were analyzed. RESULTS: A total of 77 biopsies were received
      during the nine year study period. These lesions were more frequently seen in the
      males, in a younger age group and showed a predilection for the mandible. Most of
      them presented as radiolucent, slow growing and painless lesions. Ameloblastomas
      (71.4%) constituted the majority of odontogenic tumors while central giant cell
      granulomas (7.8%) constituted the majority of giant cell lesions. CONCLUSION:
      These lesions showed a definite geographic variation with ameloblastomas being
      the most common odontogenic tumors and odontomas being relatively rarer lesions
      in our region.

PMID- 21729277
TI  - Developing and evaluating the implementation of a complex intervention: using
      mixed methods to inform the design of a randomised controlled trial of an oral
      healthcare intervention after stroke.
AB  - BACKGROUND: Many interventions delivered within the stroke rehabilitation setting
      could be considered complex, though some are more complex than others. The degree
      of complexity might be based on the number of and interactions between levels,
      components and actions targeted within the intervention. The number of (and
      variation within) participant groups and the contexts in which it is delivered
      might also reflect the extent of complexity. Similarly, designing the evaluation
      of a complex intervention can be challenging. Considerations include the
      necessity for intervention standardisation, the multiplicity of outcome measures
      employed to capture the impact of a multifaceted intervention and the delivery of
      the intervention across different clinical settings operating within varying
      healthcare contexts. Our aim was to develop and evaluate the implementation of a
      complex, multidimensional oral health care (OHC) intervention for people in
      stroke rehabilitation settings which would inform the development of a randomised
      controlled trial. METHODS: After reviewing the evidence for the provision of OHC
      following stroke, multi-disciplinary experts informed the development of our
      intervention. Using both quantitative and qualitative methods we evaluated the
      implementation of the complex OHC intervention across patients, staff and service
      levels of care. We also adopted a pragmatic approach to patient recruitment, the
      completion of assessment tools and delivery of OHC, alongside an attention to the
      context in which it was delivered. RESULTS: We demonstrated the feasibility of
      implementing a complex OHC intervention across three levels of care. The
      complementary nature of the mixed methods approach to data gathering provided a
      complete picture of the implementation of the intervention and a detailed
      understanding of the variations within and interactions between the components of
      the intervention. Information on the feasibility of the outcome measures used to
      capture impact across a range of components was also collected, though some
      process orientated uncertainties including eligibility and recruitment rates
      remain to be further explored within a Phase II exploratory trial. CONCLUSIONS:
      Complex interventions can be captured and described in a manner which facilitates
      evaluation in the form of exploratory and subsequently definitive clinical
      trials. If effective, the evidence captured relating to the intervention context
      will facilitate translation into clinical practice.

PMID- 21729278
TI  - Pontine stroke presenting as isolated facial nerve palsy mimicking Bell's palsy:
      a case report.
AB  - INTRODUCTION: Isolated facial nerve palsy usually manifests as Bell's palsy.
      Lacunar infarct involving the lower pons is a rare cause of solitary infranuclear
      facial paralysis. The present unusual case is one in which the patient appeared
      to have Bell's palsy but turned out to have a pontine infarct. CASE PRESENTATION:
      A 47-year-old Asian Indian man with a medical history of hypertension presented
      to our institution with nausea, vomiting, generalized weakness, facial droop, and
      slurred speech of 14 hours' duration. His physical examination revealed that he
      was conscious, lethargic, and had mildly slurred speech. His blood pressure was
      216/142 mmHg. His neurologic examination showed that he had loss of left-sided
      forehead creases, inability to close his left eye, left facial muscle weakness,
      rightward deviation of the angle of the mouth on smiling, and loss of the left
      nasolabial fold. Afferent corneal reflexes were present bilaterally. MRI of the
      head was initially read as negative for acute stroke. Bell's palsy appeared less
      likely because of the acuity of his presentation, encephalopathy-like imaging,
      and hypertension. The MRI was re-evaluated with a neurologist's assistance, which
      revealed a tiny 4 mm infarct involving the left dorsal aspect of the pons. The
      final diagnosis was isolated facial nerve palsy due to lacunar infarct of dorsal
      pons and hypertensive encephalopathy. CONCLUSION: The facial nerve has a
      predominant motor component which supplies all muscles concerned with unilateral
      facial expression. Anatomic knowledge is crucial for clinical localization.
      Bell's palsy accounts for around 72% of facial palsies. Other causes such as
      tumors and pontine infarcts can also present as facial palsy. Isolated dorsal
      infarct presenting as isolated facial palsy is very rare. Our case emphasizes
      that isolated facial palsy should not always be attributed to Bell's palsy. It
      can be a presentation of a rare dorsal pontine infarct as observed in our
      patient.

PMID- 21729279
TI  - Cesarean section rate in Iran, multidimensional approaches for behavioral change
      of providers: a qualitative study.
AB  - BACKGROUND: The cesarean section rate has been steadily rising from 35% in 2000
      to 40% in 2005 in Iran. The objective of this study was to identify barriers of
      reduce the cesarean section rate in Iran, as perceived by obstetricians and
      midwives as the main behavioral change target groups. METHODS: A qualitative
      study with purposive sampling was designed in which data were collected through
      in-depth interviews and document analyses. Hospitals were selected on the bases
      of being public and or private and their response to the ministry's C-section
      reduction interventions. The hospital director, obstetricians and midwives from
      each hospital were included in the study. The classification of barriers
      suggested by Grol and Wensing was used for the thematic analysis. RESULTS: After
      26 in-depth interviews and document analyses, the barriers were identified as:
      financial, insurance and judicial problems at the economic and political context
      level; the type and ownership of hospitals, absence of an on call physician,
      absence of clear job-descriptions for obstetricians and midwives, too many
      interventions in the delivery process and shortage of human resources and
      facilities at the organizational context level; distrust and insufficient
      collaborations between obstetricians and midwives from macro to micro level at
      the social context level; attitudes toward complications of C-section, reduced
      capabilities of obstetricians, midwives and residents at the individual
      professional level; and finally, at the innovation level, vaginal delivery is
      time consuming, imposes high stress levels and is unpredictable. CONCLUSION:
      Changing service providers' behavior is not possible through presentation of
      scientific evidence alone. A multi-level and multidisciplinary approach using
      behavior change theories is unavoidable. In future studies, the effect of the
      barriers should be determined to help policy makers recognize the most effective
      interventional package.

PMID- 21729280
TI  - Insecticidal activity of the essential oil from fruits and seeds of Schinus
      terebinthifolia Raddi against African malaria vectors.
AB  - BACKGROUND: Alternative insecticides for the control of malaria and filarial
      vectors are of paramount need as resistance is increasing among classes of
      insecticides currently in use in the public health sector. In this study,
      mosquitocidal activity of Schinus terebinthifolia essential oil against Anopheles
      gambiae s.s., An. arabiensis and Culex quinquefasciatus was assessed in
      laboratory, semi- field and full- field conditions METHOD: Twenty third instar
      larvae of both Anopheles gambiae s.s. and Cx. quinquefasciatus were exposed to
      different dosages of plant extract in both laboratory and semi- field
      environments. Observation of the mortality response was assessed at intervals of
      12, 24, 48 and 72 hours. Adult semi- gravid female mosquitoes were exposed to
      papers treated with S. terebinthifolia and compared with WHO standard paper
      treated with alphacypermethrin (0.05%). RESULTS: Gas chromatography, coupled to
      mass spectrometry, identified 15 compounds from S. terebinthifolia extracts, the
      most abundant identified compound was delta-3-carene (55.36%) and the least was
      gamma-elemene (0.41%). The density of the oil was found to be 0.8086 g/ml. The
      effective dosages in the insectary ranged from 202.15 to 2625.20 ppm and were
      further evaluated in the semi- field situation. In the laboratory, the mortality
      of Cx. quinquefasciatus ranged from 0.5 to 96.75% while for An. gambiae s.s it
      was from 13.75 to 97.91%. In the semi- field experiments, the mortality rates
      observed varied for both species with time and concentrations. The LC50 and LC95
      value in the laboratory was similar for both species while in the semi- field
      they were different for each. In wild, adult mosquitoes, the KT50 for S.
      terebinthifolia was 11.29 minutes while for alphacypermethrin was 19.34 minutes.
      The 24 hour mortality was found to be 100.0% for S. terebinthifolia and 75.0% for
      alphacypermethrin which was statistically significant (P < 0.001). CONCLUSION:
      The efficacy shown by essential oils of fruits and seeds of S. terebinthifolia
      has given an opportunity for further investigation of individual components of
      these plant extracts and to evaluate them in small- scale field trials.

PMID- 21729281
TI  - Fingolimod modulates microglial activation to augment markers of remyelination.
AB  - INTRODUCTION: Microglial activation in multiple sclerosis has been postulated to
      contribute to long-term neurodegeneration during disease. Fingolimod has been
      shown to impact on the relapsing remitting phase of disease by modulating
      autoreactive T-cell egress from lymph organs. In addition, it is brain penetrant
      and has been shown to exert multiple effects on nervous system cells. METHODS: In
      this study, the impact of fingolimod and other sphingosine-1-phosphate receptor
      active molecules following lysophosphotidyl choline-induced demyelination was
      examined in the rat telencephalon reaggregate, spheroid cell culture system. The
      lack of immune system components allowed elucidation of the direct effects of
      fingolimod on CNS cell types in an organotypic situation. RESULTS: Following
      demyelination, fingolimod significantly augmented expression of myelin basic
      protein in the remyelination phase. This increase was not associated with changes
      in neurofilament levels, indicating de novo myelin protein expression not
      associated with axonal branching. Myelin wrapping was confirmed morphologically
      using confocal and electron microscopy. Increased remyelination was associated
      with down-regulation of microglial ferritin, tumor necrosis factor alpha and
      interleukin 1 during demyelination when fingolimod was present. In addition,
      nitric oxide metabolites and apoptotic effectors caspase 3 and caspase 7 were
      reduced during demyelination in the presence of fingolimod. The sphingosine-1
      phosphate receptor 1 and 5 agonist BAF312 also increased myelin basic protein
      levels, whereas the sphingosine-1-phosphate receptor 1 agonist AUY954 failed to
      replicate this effect on remyelination. CONCLUSIONS: The results presented
      indicate that modulation of S1P receptors can ameliorate pathological effectors
      associated with microglial activation leading to a subsequent increase in protein
      and morphological markers of remyelination. In addition, sphingosine-1-phosphate
      receptor 5 is implicated in promoting remyelination in vitro. This knowledge may
      be of benefit for treatment of chronic microglial inflammation in multiple
      sclerosis.

PMID- 21729282
TI  - Accuracy of multi-trait genomic selection using different methods.
AB  - BACKGROUND: Genomic selection has become a very important tool in animal genetics
      and is rapidly emerging in plant genetics. It holds the promise to be
      particularly beneficial to select for traits that are difficult or expensive to
      measure, such as traits that are measured in one environment and selected for in
      another environment. The objective of this paper was to develop three models that
      would permit multi-trait genomic selection by combining scarcely recorded traits
      with genetically correlated indicator traits, and to compare their performance to
      single-trait models, using simulated datasets. METHODS: Three (SNP) Single
      Nucleotide Polymorphism based models were used. Model G and BCpi0 assumed that
      contributed (co)variances of all SNP are equal. Model BSSVS sampled SNP effects
      from a distribution with large (or small) effects to model SNP that are (or not)
      associated with a quantitative trait locus. For reasons of comparison, model A
      including pedigree but not SNP information was fitted as well. RESULTS: In terms
      of accuracies for animals without phenotypes, the models generally ranked as
      follows: BSSVS > BCpi0 > G > > A. Using multi-trait SNP-based models, the
      accuracy for juvenile animals without any phenotypes increased up to 0.10. For
      animals with phenotypes on an indicator trait only, accuracy increased up to 0.03
      and 0.14, for genetic correlations with the evaluated trait of 0.25 and 0.75,
      respectively. CONCLUSIONS: When the indicator trait had a genetic correlation
      lower than 0.5 with the trait of interest in our simulated data, the accuracy was
      higher if genotypes rather than phenotypes were obtained for the indicator trait.
      However, when genetic correlations were higher than 0.5, using an indicator trait
      led to higher accuracies for selection candidates. For different combinations of
      traits, the level of genetic correlation below which genotyping selection
      candidates is more effective than obtaining phenotypes for an indicator trait,
      needs to be derived considering at least the heritabilities and the numbers of
      animals recorded for the traits involved.

PMID- 21729283
TI  - Improved haplotype-based detection of ongoing selective sweeps towards an
      application in Arabidopsis thaliana.
AB  - BACKGROUND: The increasing amount of genome information allows us to address
      various questions regarding the molecular evolution and population genetics of
      different species. Such genome-wide data sets including thousands of individuals
      genotyped at hundreds of thousands of markers require time-efficient and powerful
      analysis methods. Demography and sampling introduce a bias into present
      population genetic tests of natural selection, which may confound results. Thus,
      a modification of test statistics is necessary to introduce time-efficient and
      unbiased analysis methods. RESULTS: We present an improved haplotype-based test
      of selective sweeps in samples of unequally related individuals. For this
      purpose, we modified existing tests by weighting the contribution of each
      individual based on its uniqueness in the entire sample. In contrast to previous
      tests, this modified test is feasible even for large genome-wide data sets of
      multiple individuals. We utilize coalescent simulations to estimate the
      sensitivity of such haplotype-based test statistics to complex demographic
      scenarios, such as population structure, population growth and bottlenecks. The
      analysis of empirical data from humans reveals different results compared to
      previous tests. Additionally, we show that our statistic is applicable to
      empirical data from Arabidopsis thaliana. Overall, the modified test leads to a
      slight but significant increase of power to detect selective sweeps among all
      demographic scenarios. CONCLUSIONS: The concept of this modification might be
      applied to other statistics in population genetics to reduce the intrinsic bias
      of demography and sampling. Additionally, the combination of different test
      statistics may further improve the performance of tests for natural selection.

PMID- 21729284
TI  - The effects of melatonin versus placebo on delirium in hip fracture patients:
      study protocol of a randomised, placebo-controlled, double blind trial.
AB  - BACKGROUND: With an ageing population, older persons become a larger part of the
      hospital population. The incidence of delirium is high in this group, and
      experiencing delirium has major short- and long-term sequelae, which makes
      prevention crucial. During delirium, a disruption of the sleep-wake cycle is
      frequently observed. Melatonin plays an important role in the regulation of the
      sleep-wake cycle, so this raised the hypothesis that alterations in the
      metabolism of melatonin might play an important role in the development of
      delirium. The aim of this article is to describe the design of a randomised,
      placebo controlled double-blind trial that is currently in progress and that
      investigates the effects of melatonin versus placebo on delirium in older,
      postoperative hip fracture patients. METHODS/DESIGN: Acutely hospitalised
      patients aged 65 years or older admitted for surgical repair of hip fracture are
      randomised (n=452) into a treatment or placebo group. Prophylactic treatment
      consists of orally administered melatonin (3 mg) at 21:00 h on five consecutive
      days. The primary outcome is the occurrence of delirium, to be diagnosed
      according to the Confusion Assessment Method, within eight days after start of
      the study medication. Secondary outcomes are delirium severity, measured by the
      Delirium Rating Scale; duration of delirium; differences in subtypes of delirium;
      differences in total length of hospital stay; total dose of antipsychotics and/or
      benzodiazepine use during delirium; and in-hospital complications. In the twelve
      month follow up visit, cognitive function is measured by a Mini-Mental state
      examination and the Informant Questionnaire on Cognitive Decline in the Elderly.
      Functional status is assessed with the Katz ADL index score (patient and family
      version) and grip strength measurement. The outcomes of these assessments are
      compared to the outcomes that were obtained during admission. DISCUSSION: The
      proposed study will contribute to our knowledge because studies on the
      prophylactic treatment of delirium with long term follow up remain scarce. The
      results may lead to a prophylactic treatment for frail older persons at high risk
      for delirium that is safe, effective, and easily implementable in daily practice.
      TRIAL REGISTRATION: Dutch Clinical Trial Registry: NTR1576.

PMID- 21729285
TI  - Structural valve deterioration of a mitral Carpentier-Edwards pericardial
      bioprosthesis in an 87-year-old woman 16 years after its implantation.
AB  - The second-generation pericardial valve, the Carpentier-Edwards perimount
      bioprosthetic (CEP) valve, shows dramatically improved durability as compared to
      the first-generation pericardial valve, and excellent performance has been
      obtained, in both the aortic and mitral positions. Especially in elderly patients
      with an implanted CEP valve, reoperation due to structural valve deterioration
      (SVD) is rarely required. Here, we report the case of an 87-year-old woman with
      an explanted CEP valve in the mitral position due to SVD, 16 years after its
      implantation.

PMID- 21729286
TI  - Protein functional links in Trypanosoma brucei, identified by gene fusion
      analysis.
AB  - BACKGROUND: Domain or gene fusion analysis is a bioinformatics method for
      detecting gene fusions in one organism by comparing its genome to that of other
      organisms. The occurrence of gene fusions suggests that the two original genes
      that participated in the fusion are functionally linked, i.e. their gene products
      interact either as part of a multi-subunit protein complex, or in a metabolic
      pathway. Gene fusion analysis has been used to identify protein functional links
      in prokaryotes as well as in eukaryotic model organisms, such as yeast and
      Drosophila. RESULTS: In this study we have extended this approach to include a
      number of recently sequenced protists, four of which are pathogenic, to identify
      fusion linked proteins in Trypanosoma brucei, the causative agent of African
      sleeping sickness. We have also examined the evolution of the gene fusion events
      identified, to determine whether they can be attributed to fusion or fission, by
      looking at the conservation of the fused genes and of the individual component
      genes across the major eukaryotic and prokaryotic lineages. We find relatively
      limited occurrence of gene fusions/fissions within the protist lineages examined.
      Our results point to two trypanosome-specific gene fissions, which have recently
      been experimentally confirmed, one fusion involving proteins involved in the same
      metabolic pathway, as well as two novel putative functional links between fusion
      linked protein pairs. CONCLUSIONS: This is the first study of protein functional
      links in T. brucei identified by gene fusion analysis. We have used strict
      thresholds and only discuss results which are highly likely to be genuine and
      which either have already been or can be experimentally verified. We discuss the
      possible impact of the identification of these novel putative protein-protein
      interactions, to the development of new trypanosome therapeutic drugs.

PMID- 21729287
TI  - Amino-terminal extension present in the methionine aminopeptidase type 1c of
      Mycobacterium tuberculosis is indispensible for its activity.
AB  - BACKGROUND: Methionine aminopeptidase (MetAP) is a ubiquitous enzyme in both
      prokaryotes and eukaryotes, which catalyzes co-translational removal of N
      terminal methionine from elongating polypeptide chains during protein synthesis.
      It specifically removes the terminal methionine in all organisms, if the
      penultimate residue is non-bulky and uncharged. The MetAP action for exclusion of
      N-terminal methionine is mandatory in 50-70% of nascent proteins. Such an
      activity is required for proper sub cellular localization, additional processing
      and eventually for the degradation of proteins. RESULTS: We cloned genes encoding
      two such metalloproteases (MtMetAP1a and MtMetAP1c) present in Mycobacterium
      tuberculosis and expressed them as histidine-tagged proteins in Escherichia coli.
      Although they have different substrate preferences, for Met-Ala-Ser, we found,
      MtMetAP1c had significantly high enzyme turnover rate as opposed to MtMetAP1a.
      Circular dichroism spectroscopic studies as well as monitoring of enzyme activity
      indicated high temperature stability (up to 50  degrees C) of MtMetAP1a compared
      to that of the MtMetAP1c. Modelling of MtMetAP1a based on MtMetAP1c crystal
      structure revealed the distinct spatial arrangements of identical active site
      amino acid residues and their mutations affected the enzymatic activities of both
      the proteins. Strikingly, we observed that 40 amino acid long N-terminal
      extension of MtMetAP1c, compared to its other family members, contributes towards
      the activity and stability of this enzyme, which has never been reported for any
      methionine aminopeptidase. Furthermore, mutational analysis revealed that Val-18
      and Pro-19 of MtMetAP1c are crucial for its enzymatic activity. Consistent with
      this observation, molecular dynamic simulation studies of wild-type and these
      variants strongly suggest their involvement in maintaining active site
      conformation of MtMetAP1c. CONCLUSION: Our findings unequivocally emphasized that
      N-terminal extension of MtMetAP1c contributes towards the functionality of the
      enzyme presumably by regulating active site residues through "action-at-a
      distance" mechanism and we for the first time are reporting this unique function
      of the enzyme.

PMID- 21729288
TI  - CCL2/MCP-1 modulation of microglial activation and proliferation.
AB  - BACKGROUND: Monocyte chemoattractant protein (CCL2/MCP-1) is a chemokine that
      attracts cells involved in the immune/inflammatory response. As microglia are one
      of the main cell types sustaining inflammation in brain, we proposed here to
      analyze the direct effects of MCP-1 on cultured primary microglia. METHODS:
      Primary microglia and neuronal cultures were obtained from neonatal and embryonic
      Wistar rats, respectively. Microglia were incubated with different concentrations
      of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring
      incorporation of bromodeoxyuridine (BrdU). Nitrite accumulation was measured
      using the Griess assay. The expression and synthesis of different proteins was
      measured by RT-PCR and ELISA. Cell death was quantified by measuring release of
      LDH into the culture medium. RESULTS: MCP-1 treatment (50 ng/ml, 24 h) did not
      induce morphological changes in microglial cultures. Protein and mRNA levels of
      different cytokines were measured, showing that MCP-1 was not able to induce
      proinflammatory cytokines (IL-1beta, IL6, MIP-1alpha), either by itself or in
      combination with LPS. A similar lack of effect was observed when measuring
      inducible nitric oxide synthase (NOS2) expression or accumulation of nitrites in
      the culture media as a different indicator of microglial activation. MCP-1 was
      also unable to alter the expression of different trophic factors that were
      reduced by LPS treatment. In order to explore the possible release of other
      products by microglia and their potential neurotoxicity, neurons were co-cultured
      with microglia: no death of neurons could be detected when treated with MCP-1.
      However, the presence of MCP-1 induced proliferation of microglia, an effect
      opposite to that observed with LPS. CONCLUSION: These data indicate that, while
      causing migration and proliferation of microglia, MCP-1 does not appear to
      directly activate an inflammatory response in this cell type, and therefore,
      other factors may be necessary to cause the changes that result in the neuronal
      damage commonly observed in situations where MCP-1 levels are elevated.

PMID- 21729289
TI  - Unnecessary use of fluoroquinolone antibiotics in hospitalized patients.
AB  - BACKGROUND: Fluoroquinolones are among the most commonly prescribed
      antimicrobials and are an important risk factor for colonization and infection
      with fluoroquinolone-resistant gram-negative bacilli and for Clostridium
      difficile infection (CDI). In this study, our aim was to determine current
      patterns of inappropriate fluoroquinolone prescribing among hospitalized
      patients, and to test the hypothesis that longer than necessary treatment
      durations account for a significant proportion of unnecessary fluoroquinolone
      use. METHODS: We conducted a 6-week prospective, observational study to determine
      the frequency of, reasons for, and adverse effects associated with unnecessary
      fluoroquinolone use in a tertiary-care academic medical center. For randomly
      selected adult inpatients receiving fluoroquinolones, therapy was determined to
      be necessary or unnecessary based on published guidelines or standard principles
      of infectious diseases. Adverse effects were determined based on chart review 6
      weeks after completion of therapy. RESULTS: Of 1,773 days of fluoroquinolone
      therapy, 690 (39%) were deemed unnecessary. The most common reasons for
      unnecessary therapy included administration of antimicrobials for non-infectious
      or non-bacterial syndromes (292 days-of-therapy) and administration of
      antimicrobials for longer than necessary durations (234 days-of-therapy). The
      most common syndrome associated with unnecessary therapy was urinary tract
      infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy).
      Twenty-seven percent (60/227) of regimens were associated with adverse effects
      possibly attributable to therapy, including gastrointestinal adverse effects (14%
      of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4%
      of regimens). CONCLUSIONS: In our institution, 39% of all days of fluoroquinolone
      therapy were unnecessary. Interventions that focus on improving adherence with
      current guidelines for duration of antimicrobial therapy and for management of
      urinary syndromes could significantly reduce overuse of fluoroquinolones.

PMID- 21729290
TI  - Effects of simvastatin on apolipoprotein M in vivo and in vitro.
AB  - OBJECTIVE: To investigate effects of lipid lowering drug, simvastatin, on
      apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line,
      HepG2 cells. METHODS: Swiss male mice were randomly divided into the high fat
      group and control group, and were intragastrically fed with 0.9% saline (control
      group) or lipid emulsion (high fat group) at the daily dosage of 15 ml/kg body
      weight, respectively. After 8 weeks feeding, the hyperlipidemic model was
      successfully induced and these hyperlipidemic mice were then randomly divided
      into three experimental groups: vehicle control group, high-dose simvastatin
      treated group (100 mg/kg body weight), and low-dose simvastatin-treated group (10
      mg/kg body weight). Mice were dosed daily for 6 weeks of simvastatin before mice
      were sacrificed for determining serum lipid profile and apoM protein levels that
      was determined by using dot blotting analysis. Effects of simvastatin on apoM
      mRNA expression in the HepG2 cells were determined by real-time RT-PCR. RESULTS:
      Comparing to high fat model mice without simvastatin treatment, 100 mg/kg
      simvastatin could significantly increase serum total cholesterol (P < 0.05).
      Serum apoM levels, in all mice, were significantly lower in the mice at the age
      of 26 weeks than the mice at 12 weeks old (P < 0.05), which indicated that serum
      apoM levels were significantly correlated to the mice age. It demonstrated also
      that treatment of simvastatin did not influence serum apoM levels in these mouse
      model, although serum apoM levels were increased by about 13% in the 10 mg/kg
      simvastatin group than in the vehicle control group without simvastatin. In HepG2
      cell cultures, simvastatin could significantly decrease apoM mRNA levels with
      dose- and time-dependent manners. At 10 MUM simvastatin treatment, apoM mRNA
      decreased by 52% compared to the controls. CONCLUSION: The present study
      suggested that simvastatin, in vivo, had no effect on apoM levels in the
      hyperlipidemic mouse model. ApoM serum levels in mice were significantly
      correlated to the animal's age, whereas in cell cultures simvastatin does inhibit
      apoM expression in the HepG2 cells. The mechanism behind it is not known yet.

PMID- 21729291
TI  - Hepatic oxidative stress in an animal model of sleep apnoea: effects of different
      duration of exposure.
AB  - BACKGROUND: Repeated apnoea events cause intermittent hypoxia (IH), which alters
      the function of various systems and produces free radicals and oxidative stress.
      METHODS: We investigated hepatic oxidative stress in adult mice subjected to
      intermittent hypoxia, simulating sleep apnoea. Three groups were submitted to 21
      days of IH (IH-21), 35 days of IH (IH-35), or 35 days of sham IH. We assessed the
      oxidative damage to lipids by TBARS and to DNA by comet assay; hepatic tissue
      inflammation was assessed in HE-stained slides. Antioxidants were gauged by
      catalase, superoxide dismutase, glutathione peroxidase activity and by total
      glutathione. RESULTS: After IH-21, no significant change was observed in hepatic
      oxidative stress. After IH-35, significant oxidative stress, lipid peroxidation,
      DNA damage and reduction of endogenous antioxidants were detected. CONCLUSIONS:
      In an animal model of sleep apnoea, intermittent hypoxia causes liver damage due
      to oxidative stress after 35 days, but not after 21 days.

PMID- 21729292
TI  - Combined logical and data-driven models for linking signalling pathways to
      cellular response.
AB  - BACKGROUND: Signalling pathways are the cornerstone on understanding cell
      function and predicting cell behavior. Recently, logical models of canonical
      pathways have been optimised with high-throughput phosphoproteomic data to
      construct cell-type specific pathways. However, less is known on how signalling
      pathways can be linked to a cellular response such as cell growth, death,
      cytokine secretion, or transcriptional activity. RESULTS: In this work, we
      measure the signalling activity (phosphorylation levels) and phenotypic behavior
      (cytokine secretion) of normal and cancer hepatocytes treated with a combination
      of cytokines and inhibitors. Using the two datasets, we construct "extended"
      pathways that integrate intracellular activity with cellular responses using a
      hybrid logical/data-driven computational approach. Boolean logic is used whenever
      a priori knowledge is accessible (i.e., construction of canonical pathways),
      whereas a data-driven approach is used for linking cellular behavior to
      signalling activity via non-canonical edges. The extended pathway is subsequently
      optimised to fit signalling and behavioural data using an Integer Linear
      Programming formulation. As a result, we are able to construct maps of primary
      and transformed hepatocytes downstream of 7 receptors that are capable of
      explaining the secretion of 22 cytokines. CONCLUSIONS: We developed a method for
      constructing extended pathways that start at the receptor level and via a complex
      intracellular signalling pathway identify those mechanisms that drive cellular
      behaviour. Our results constitute a proof-of-principle for construction of
      "extended pathways" that are capable of linking pathway activity to diverse
      responses such as growth, death, differentiation, gene expression, or cytokine
      secretion.

PMID- 21729293
TI  - Immunomodulator expression in trophoblasts from the feline immunodeficiency virus
      (FIV)-infected cat.
AB  - BACKGROUND: FIV infection frequently compromises pregnancy under experimental
      conditions and is accompanied by aberrant expression of some placental cytokines.
      Trophoblasts produce numerous immunomodulators that play a role in placental
      development and pregnancy maintenance. We hypothesized that FIV infection may
      cause dysregulation of trophoblast immunomodulator expression, and aberrant
      expression of these molecules may potentiate inflammation and compromise
      pregnancy. The purpose of this project was to evaluate the expression of
      representative pro-(TNF-alpha, IFN-gamma, IL-1beta, IL-2, IL-6, IL-12p35, IL
      12p40, IL-18, and GM-CSF) and anti-inflammatory cytokines (IL-4, IL-5, and IL
      10); CD134, a secondary co-stimulatory molecule expressed on activated T cells
      (FIV primary receptor); the chemokine receptor CXCR4 (FIV co-receptor); SDF
      1alpha, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and
      late-term pregnancy. METHODS: We used an anti-cytokeratin antibody in
      immunohistochemistry to identify trophoblasts selectively, collected these cells
      using laser capture microdissection, and extracted total RNA from the captured
      cell populations. Real time, reverse transcription-PCR was used to quantify gene
      expression. RESULTS: We detected IL-4, IL-5, IL-6, IL-1beta, IL-12p35, IL-12p40,
      and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of
      cytokines increased from early to late pregnancy in normal tissues. A clear, pro
      inflammatory microenvironment was not evident in trophoblasts from FIV-infected
      queens at either stage of pregnancy. Reproductive failure was accompanied by down
      regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in
      trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens
      collected from FIV-infected queens. CONCLUSION: Feline trophoblasts express an
      array of pro-and anti-inflammatory immunomodulators whose expression increases
      from early to late pregnancy in normal tissues. Non-viable pregnancies were
      associated with decreased expression of immunomodulators which regulate
      trophoblast invasion in other species. The detection of FIV RNA in trophoblasts
      was rare, suggesting that the high rate of reproductive failure in FIV-infected
      queens was not a direct result of viral replication in trophoblasts. The
      influence of placental immune cells on trophoblast function and pregnancy
      maintenance in the FIV-infected cat requires additional study.

PMID- 21729294
TI  - Status and risk factors of unintentional injuries among Chinese undergraduates: a
      cross-sectional study.
AB  - BACKGROUND: Injuries affect all age groups but have a particular impact on young
      people. To evaluate the incidence of non-fatal, unintentional, injuries among
      undergraduates in Wenzhou, China, assess the burden caused by these injuries, and
      explore the associated risk factors for unintentional injuries among these
      undergraduates, we conducted a college-based cross-sectional study. METHODS:
      Participants were selected by a multi-stage random sampling method, and 2,287
      students were asked whether they had had an injury in the last 12 months; the
      location, cause, and consequences of the event. The questionnaire included
      demographic and socioeconomic characteristics, lifestyle habits, and the scale of
      type A behaviour pattern (TABP). Multivariate logistic regression models were
      used; crude odds ratios (ORs), adjusted ORs and their 95% confidence intervals
      (CIs) were estimated, with students having no injuries as the reference group.
      RESULTS: The incidence of injuries among undergraduates in Wenzhou was 18.71
      injuries per 100 person-years (95%CI: 17.12~20.31 injuries per 100 person-years).
      Falls were the leading cause of injury, followed by traffic injuries, and
      animal/insect bites. Male students were more likely to be injured than female
      students. Risk factors associated with unintentional injuries among
      undergraduates were: students majoring in non-medicine (adjusted OR: 1.53; 95%
      CI: 1.19-1.96); type A behaviour pattern (adjusted OR: 2.99; 95% CI: 1.45-6.14);
      liking sports (adjusted OR: 1.86; 95% CI: 1.41-2.45). CONCLUSIONS: Injuries have
      become a public health problem among undergraduates. Falls were the major cause
      of non-fatal injury. Therefore, individuals, families, schools and governments
      should promptly adopt preventive measures aimed at preventing and controlling
      morbidity due to non-fatal injury, especially among students identified to be at
      high-risk; such as male students with type A behaviour pattern who like sports.

PMID- 21729296
TI  - Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a
      case report.
AB  - INTRODUCTION: Acute intoxication with drugs of abuse in children is often only
      the tip of the iceberg, actually hiding chronic exposure. Analysis using non
      conventional matrices such as hair can provide long-term information about
      exposure to recreational drugs. CASE PRESENTATION: We report the case of a one
      month-old Caucasian boy admitted to our pediatric emergency unit with respiratory
      distress and neurological abnormalities. A routine urine test was positive for
      opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as
      cocaine, cannabis, amphetamines or derivatives, were detected in the baby's
      urine. Subsequently, hair samples from the baby and the parents were collected to
      evaluate the possibility of chronic exposure to drug misuse by segmental
      analysis. Opiates and cocaine metabolites were detected in hair samples from the
      baby boy and his parents. CONCLUSIONS: In light of these and previous results, we
      recommend hair analysis in babies and children from risky environments to detect
      exposure to heroin and other drug misuse, which could provide the basis for
      specific social and health interventions.

PMID- 21729295
TI  - Comparative analysis of methods for detecting interacting loci.
AB  - BACKGROUND: Interactions among genetic loci are believed to play an important
      role in disease risk. While many methods have been proposed for detecting such
      interactions, their relative performance remains largely unclear, mainly because
      different data sources, detection performance criteria, and experimental
      protocols were used in the papers introducing these methods and in subsequent
      studies. Moreover, there have been very few studies strictly focused on
      comparison of existing methods. Given the importance of detecting gene-gene and
      gene-environment interactions, a rigorous, comprehensive comparison of
      performance and limitations of available interaction detection methods is
      warranted. RESULTS: We report a comparison of eight representative methods, of
      which seven were specifically designed to detect interactions among single
      nucleotide polymorphisms (SNPs), with the last a popular main-effect testing
      method used as a baseline for performance evaluation. The selected methods,
      multifactor dimensionality reduction (MDR), full interaction model (FIM),
      information gain (IG), Bayesian epistasis association mapping (BEAM), SNP
      harvester (SH), maximum entropy conditional probability modeling (MECPM),
      logistic regression with an interaction term (LRIT), and logistic regression (LR)
      were compared on a large number of simulated data sets, each, consistent with
      complex disease models, embedding multiple sets of interacting SNPs, under
      different interaction models. The assessment criteria included several relevant
      detection power measures, family-wise type I error rate, and computational
      complexity. There are several important results from this study. First, while
      some SNPs in interactions with strong effects are successfully detected, most of
      the methods miss many interacting SNPs at an acceptable rate of false positives.
      In this study, the best-performing method was MECPM. Second, the statistical
      significance assessment criteria, used by some of the methods to control the type
      I error rate, are quite conservative, thereby limiting their power and making it
      difficult to fairly compare them. Third, as expected, power varies for different
      models and as a function of penetrance, minor allele frequency, linkage
      disequilibrium and marginal effects. Fourth, the analytical relationships between
      power and these factors are derived, aiding in the interpretation of the study
      results. Fifth, for these methods the magnitude of the main effect influences the
      power of the tests. Sixth, most methods can detect some ground-truth SNPs but
      have modest power to detect the whole set of interacting SNPs. CONCLUSION: This
      comparison study provides new insights into the strengths and limitations of
      current methods for detecting interacting loci. This study, along with freely
      available simulation tools we provide, should help support development of
      improved methods. The simulation tools are available at:
      http://code.google.com/p/simulation-tool-bmc-ms9169818735220977/downloads/list.

PMID- 21729297
TI  - Visual detection of H3 subtype avian influenza viruses by reverse transcription
      loop-mediated isothermal amplification assay.
AB  - BACKGROUND: Recent epidemiological investigation of different HA subtypes of
      avian influenza viruses (AIVs) shows that the H3 subtype is the most predominant
      among low pathogenic AIVs (LPAIVs), and the seasonal variations in isolation of
      H3 subtype AIVs are consistent with that of human H3 subtype influenza viruses.
      Consequently, the development of a rapid, simple, sensitive detection method for
      H3 subtype AIVs is required. The loop-mediated isothermal amplification (LAMP)
      assay is a simple, rapid, sensitive and cost-effective nucleic acid amplification
      method that does not require any specialized equipment. RESULTS: A reverse
      transcription loop-mediated isothermal amplification (RT-LAMP) assay was
      developed to detect the H3 subtype AIVs visually. Specific primer sets target the
      sequences of the hemagglutinin (HA) gene of H3 subtype AIVs were designed, and
      assay reaction conditions were optimized. The established assay was performed in
      a water bath for 50 minutes, and the amplification result was visualized directly
      as well as under ultraviolet (UV) light reflections. The detection limit of the
      RT-LAMP assay was 0.1pg total RNA of virus, which was one hundred-fold higher
      than that of RT-PCR. The results on specificity indicated that the assay had no
      cross-reactions with other subtype AIVs or avian respiratory pathogens.
      Furthermore, a total of 176 clinical samples collected from birds at the various
      live-bird markets (LBMs) were subjected to the H3-subtype-specific RT-LAMP (H3-RT
      LAMP). Thirty-eight H3 subtype AIVs were identified from the 176 clinical samples
      that were consistent with that of virus isolation. CONCLUSIONS: The newly
      developed H3-RT-LAMP assay is simple, sensitive, rapid and can identify H3
      subtype AIVs visually. Consequently, it will be a very useful screening assay for
      the surveillance of H3 subtype AIVs in underequipped laboratories as well as in
      field conditions.

PMID- 21729298
TI  - An industry consensus study on an HPLC fluorescence method for the determination
      of (+/-)-catechin and (+/-)-epicatechin in cocoa and chocolate products.
AB  - BACKGROUND: This manuscript describes the results of an HPLC study for the
      determination of the flavan-3-ol monomers, (+/-)-catechin and (+/-)-epicatechin,
      in cocoa and plain dark and milk chocolate products. The study was performed
      under the auspices of the National Confectioners Association (NCA) and involved
      the analysis of a series of samples by laboratories of five member companies
      using a common method. METHODOLOGY: The method reported in this paper uses
      reversed phase HPLC with fluorescence detection to analyze (+/-)-epicatechin and
      (+/-)-catechin extracted with an acidic solvent from defatted cocoa and
      chocolate. In addition to a variety of cocoa and chocolate products, the sample
      set included a blind duplicate used to assess method reproducibility. All data
      were subjected to statistical analysis with outliers eliminated from the data
      set. RESULTS: The percent coefficient of variation (%CV) of the sample set ranged
      from approximately 7 to 15%. CONCLUSIONS: Further experimental details are
      described in the body of the manuscript and the results indicate the method is
      suitable for the determination of (+/-)-catechin and (+/-)-epicatechin in cocoa
      and chocolate products and represents the first collaborative study of this HPLC
      method for these compounds in these matrices.

PMID- 21729299
TI  - Alertness can be improved by an interaction between orienting attention and
      alerting attention in schizophrenia.
AB  - BACKGROUND: Attention is impaired in schizophrenia. Early attention components
      include orienting and alerting, as well as executive control networks. Previous
      studies have shown mainly executive control deficits, while few of them found
      orienting and alerting abnormalities. Here we explore the different attentive
      networks, their modulation and interactions in patients with schizophrenia.
      METHODS: Twenty-one schizophrenic patients (DSMIV), compared to 21 controls,
      performed a modified version of the Attention Network Task, in which an orienting
      paradigm (with valid, invalid and no cues) was combined with a flanker task
      (congruent/incongruent) and an alerting signal (tone/no tone), to assess
      orienting, executive control and alerting networks independently. RESULTS:
      Patients showed an abnormal alerting effect and slower overall reaction time
      compared to controls. Moreover, there was an interaction between orienting and
      alerting: patients are helped more than controls by the alerting signal in a
      valid orientation to solve the incongruent condition. CONCLUSION: These results
      suggest that patients with schizophrenia have altered alerting abilities.
      However, the orienting and alerting cues interact to improve their attention
      performance in the resolution of conflict, creating possibilities for cognitive
      remediation strategies.

PMID- 21729301
TI  - Modification by antioxidant supplementation of changes in human lung function
      associated with air pollutant exposure: a systematic review.
AB  - BACKGROUND: Outdoor air pollution, given its demonstrated negative effects on the
      respiratory system, is a growing public health concern worldwide, particularly in
      urban cities. Human exposure to pollutants such as ozone, nitrogen oxides,
      combustion-related particulate matter and oxides of sulfur is responsible for
      significant cardiopulmonary morbidity and mortality in both adults and children.
      Several antioxidants have shown an ability to partially attenuate the negative
      physiological and functional impacts of air pollutants. This study systematically
      presents current data on the potential benefits of antioxidant supplementation on
      lung function outcomes associated with air pollutant exposures in intact humans.
      METHODS: Electronic databases (MEDLINE, EMBASE, BIOSIS Previews, Web of Sciences,
      Environmental Sciences & Pollution Management and TOXNET) were systematically
      searched for all studies published up to April 2009. Search terms relating to the
      concepts of respiratory tract diseases, respiratory function tests, air
      pollution, and antioxidants were used. Data was systematically abstracted from
      original articles that satisfied selection criteria for inclusion. For inclusion,
      the studies needed to have evaluated human subjects, given supplemental
      antioxidants, under conditions of known levels of air pollutants with measured
      lung function before and after antioxidant administration and/or air pollution
      exposure. Selected studies were summarized and conclusions presented. RESULTS:
      Eight studies investigated the role of antioxidant supplementation on measured
      lung function outcomes after subject exposure to air pollutants under controlled
      conditions; 5 of these studies concluded that pollutant-induced airway hyper
      responsiveness and diminution in lung function measurements were attenuated by
      antioxidant supplementation. The remaining five studies took place under ambient
      (uncontrolled) exposures and unanimously concluded that antioxidant
      supplementations attenuate the negative effects of urban air pollution on lung
      function. CONCLUSIONS: The data evaluating modification of changes in lung
      function associated with air pollutant exposure by antioxidant supplementation,
      in intact humans, is limited. Of 13 studies dedicated to this concern, ten
      demonstrated an attenuation of pollution-associated decrements. There is growing
      evidence for the benefit of anti-oxidant supplementation in moderating the
      effects of air pollution on lung function, but more research on human
      participants is needed to inform this topic.

PMID- 21729302
TI  - Bradykinin promotes migration and invasion of human immortalized trophoblasts.
AB  - Having demonstrated that the bradykinin B2 receptor (B2R) is expressed in cells
      that participate in trophoblast invasion in humans and guinea-pigs, we
      investigated the role of bradykinin (BK) on cell migration and invasion in the
      HTR-8/SVneo trophoblast cell line using wound healing and invasion assays. First,
      we documented that HTR-8/SVneo cells expressed kallikrein, B2R, B1R, MMP-2 and
      MMP-9 using immunocytochemistry. Incubation with BK (10.0 microMol/L) for 18
      hours increased the migration index 3-fold in comparison to controls or to cells
      preincubated with the B2R antagonist HOE-140. BK (10.0 microMol/L) incubation
      yielded a similar number of proliferating and viable cells as controls, therefore
      the enhanced closure of the wound cannot be attributed to proliferating cells.
      Incubation with BK (10.0 microMol/L) for 18 hours increased the invasion index 2
      fold in comparison to controls or to cells preincubated with the antagonist of
      the B2R. Neither the B1R ligand Lys-des-Arg9 BK, nor its antagonist Lys-(des-Arg9
      Leu8), modified migration and invasion. Further support for the stimulatory
      effect of B2R activation on migration and invasion is provided by the 3-fold
      increase in the number of filopodia per cell versus controls or cells
      preincubated with the B2R antagonist. Bradykinin had no effect on the cellular
      protein content of the B2R, nor the MMP-9 and MMP-2 gelatinase activity in the
      culture media varied after incubation with BK. This study adds bradykinin-acting
      on the B2R-to the stimuli of trophoblast migration and invasion, an effect that
      should be integrated to other modifications of the kallikrein-kinin system in
      normal and pathological pregnancies.

PMID- 21729303
TI  - Race/Ethnicity and gender differences in health intentions and behaviors
      regarding exercise and diet for adults with type 2 diabetes: a cross-sectional
      analysis.
AB  - BACKGROUND: Self-management is the cornerstone of diabetes control and prevention
      of complications; however, it is undetermined whether differences in intention to
      adopt healthy lifestyles and actual healthy behavior exist across race/ethnic
      groups. This study evaluated the differences across racial-ethnic groups in self
      reported medical advice received and health intentions and behaviors among adults
      with type 2 diabetes mellitus. METHODS: A cross-sectional analysis of the 2007
      SHIELD US survey ascertained self-reported health intentions and behaviors for
      regular exercise, diet, and weight management among Non-Hispanic Caucasian (n =
      2526), Non-Hispanic African-American (n = 706), and Hispanic (n = 179)
      respondents with type 2 diabetes. RESULTS: A similar proportion of respondents
      from each race-gender group (43%-56%) reported receiving healthcare advice to
      increase their exercise (P = 0.32). Significantly more minorities reported an
      intention to follow the exercise recommendation compared with Non-Hispanic
      Caucasians (P = 0.03). More Non-Hispanic African-American (29%) and Hispanic
      (27%) men reported exercising regularly compared with other race-gender groups (P
      = 0.02). Significantly more Non-Hispanic Caucasian women (74%) and Hispanic women
      (79%) reported trying to lose weight compared with other groups (P < 0.0001).
      CONCLUSIONS: Differences in health intentions and healthy behaviors were noted
      across race-gender groups. More Non-Hispanic African-American men reported an
      intention to follow advice on exercising and self-report of exercising regularly
      was also higher compared with other race-gender groups. More Hispanic men
      reported high physical activity levels than other groups. Despite an increased
      willingness to follow healthcare recommendations for diet, >50% of respondents
      were obese among all race-gender groups.

PMID- 21729304
TI  - Expression and prognostic value of circulating angiogenic cytokines in pancreatic
      cancer.
AB  - BACKGROUND: The utility of circulating angiogenic cytokines (CAC) as biomarkers
      in pancreatic cancer has not been clarified yet. We investigated the expression
      and prognostic associations of seven CAC in patients with pancreatic cancer.
      METHODS: Serum samples were collected preoperatively in patients undergoing
      surgery for localized pancreatic cancer (n = 74), metastatic pancreatic cancer (n
      = 24) or chronic pancreatitis (n = 20) and in healthy controls (n = 48).
      Quantitative enzyme-linked immunosorbent assays and multiplex protein arrays were
      used to determine circulating levels of VEGF, VEGFR-1, PlGF, PDGF-AA, PDGF-BB,
      Ang-1 and EGF. Multivariate analyses on cancer-specific survival were performed
      with a Cox proportional hazards model. RESULTS: VEGF (p < 0.0001), PDGF-AA (p <
      0.0001), Ang-1 (p = 0.002) and EGF (p < 0.0001) were differentially expressed in
      patients with pancreatic cancer compared to healthy controls. The presence of
      lymph node metastases was associated with increased levels of all CAC except for
      PlGF, whereas there were only minor associations of CAC with other
      clinicopathologic variables. The multivariate model including the entire
      angiogenic panel revealed high levels of circulating PDGF-AA (hazard ratio 4.58;
      95% confidence interval 1.43 - 14.69) as predictor of poor cancer-specific
      survival, whereas high levels of PDGF-BB (0.15; 0.15 - 0.88), Ang-1 (0.30; 0.10 -
      0.93) and VEGF (0.24; 0.09 - 0.57) were associated with a favorable prognosis.
      CONCLUSION: Circulating levels of certain angiogenic cytokines correlate with
      patients' prognosis after resection for pancreatic cancer, if a panel of several
      CAC is considered simultaneously. These data should be considered in future
      studies evaluating angiogenic factors as prognostic biomarkers and therapeutic
      targets in patients with pancreatic cancer.

PMID- 21729305
TI  - Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher
      grade of cervical intraepithelial neoplasia.
AB  - BACKGROUND: D2-40 has been shown a selective marker for lymphatic endothelium,
      but also shown in the benign cervical basal cells. However, the application of D2
      40 immunoreactivity in the cervical basal cells for identifying the grade of
      cervical intraepithelial neoplasia (CIN) has not been evaluated. METHODS: In this
      study, the immunoreactive patterns of D2-40, compared with p16(INK4A), which is
      currently considered as the useful marker for cervical cancers and their
      precancerous diseases, were examined in total 125 cervical specimens including 32
      of CIN1, 37 of CIN2, 35 of CIN3, and 21 of normal cervical tissue. D2-40 and
      p16(INK4A) immunoreactivities were scored semiquantitatively according to the
      intensity and/or extent of the staining. RESULTS: Diffuse D2-40 expression with
      moderate-to-strong intensity was seen in all the normal cervical epithelia
      (21/21, 100%) and similar pattern of D2-40 immunoreactivity with weak-to-strong
      intensity was observed in CIN1 (31/32, 97.2%). However, negative and/or focal D2
      40 expression was found in CIN2 (negative: 20/37, 54.1%; focal: 16/37, 43.2%) and
      CIN3 (negative: 22/35, 62.8%; focal: 12/35, 34.3%). On the other hand, diffuse
      immunostaining for p16(INK4A) was shown in 37.5% of CIN1, 64.9% of CIN2, and
      80.0% of CIN3. However, the immunoreactive pattern of D2-40 was not associated
      with the p16(INK4A) immunoreactivity. CONCLUSIONS: Immunohistochemical analysis
      of D2-40 combined with p16(INK4A) may have a significant implication in clinical
      practice for better identifying the grade of cervical intraepithelial neoplasia,
      especially for distinguishing CIN1 from CIN2/3.

PMID- 21729306
TI  - Gatekeeper of pluripotency: a common Oct4 transcriptional network operates in
      mouse eggs and embryonic stem cells.
AB  - BACKGROUND: Oct4 is a key factor of an expanded transcriptional network (Oct4-TN)
      that governs pluripotency and self-renewal in embryonic stem cells (ESCs) and in
      the inner cell mass from which ESCs are derived. A pending question is whether
      the establishment of the Oct4-TN initiates during oogenesis or after
      fertilisation. To this regard, recent evidence has shown that Oct4 controls a
      poorly known Oct4-TN central to the acquisition of the mouse egg developmental
      competence. The aim of this study was to investigate the identity and extension
      of this maternal Oct4-TN, as much as whether its presence is circumscribed to the
      egg or maintained beyond fertilisation. RESULTS: By comparing the genome-wide
      transcriptional profile of developmentally competent eggs that express the OCT4
      protein to that of developmentally incompetent eggs in which OCT4 is down
      regulated, we unveiled a maternal Oct4-TN of 182 genes. Eighty of these
      transcripts escape post-fertilisation degradation and represent the maternal Oct4
      TN inheritance that is passed on to the 2-cell embryo. Most of these 80 genes are
      expressed in cancer cells and 37 are notable companions of the Oct4 transcriptome
      in ESCs. CONCLUSIONS: These results provide, for the first time, a developmental
      link between eggs, early preimplantation embryos and ESCs, indicating that the
      molecular signature that characterises the ESCs identity is rooted in oogenesis.
      Also, they contribute a useful resource to further study the mechanisms of Oct4
      function and regulation during the maternal-to-embryo transition and to explore
      the link between the regulation of pluripotency and the acquisition of de
      differentiation in cancer cells.

PMID- 21729307
TI  - A new permanent cell line derived from the bank vole (Myodes glareolus) as cell
      culture model for zoonotic viruses.
AB  - BACKGROUND: Approximately 60% of emerging viruses are of zoonotic origin, with
      three-fourths derived from wild animals. Many of these zoonotic diseases are
      transmitted by rodents with important information about their reservoir dynamics
      and pathogenesis missing. One main reason for the gap in our knowledge is the
      lack of adequate cell culture systems as models for the investigation of rodent
      borne (robo) viruses in vitro. Therefore we established and characterized a new
      cell line, BVK168, using the kidney of a bank vole, Myodes glareolus, the most
      abundant member of the Arvicolinae trapped in Germany. RESULTS: BVK168 proved to
      be of epithelial morphology expressing tight junctions as well as adherence
      junction proteins. The BVK168 cells were analyzed for their infectability by
      several arbo- and robo-viruses: Vesicular stomatitis virus, vaccinia virus,
      cowpox virus, Sindbis virus, Pixuna virus, Usutu virus, Inkoo virus,
      Puumalavirus, and Borna disease virus (BDV). The cell line was susceptible for
      all tested viruses, and most interestingly also for the difficult to propagate
      BDV. CONCLUSION: In conclusion, the newly established cell line from wildlife
      rodents seems to be an excellent tool for the isolation and characterization of
      new rodent-associated viruses and may be used as in vitro-model to study
      properties and pathogenesis of these agents.

PMID- 21729308
TI  - The efficacy of hypotonic and near-isotonic saline for parenteral fluid therapy
      given at low maintenance rate in preventing significant change in plasma sodium
      in post-operative pediatric patients: protocol for a prospective randomized non
      blinded study.
AB  - BACKGROUND: Hyponatremia is the most frequent electrolyte abnormality observed in
      post-operative pediatric patients receiving intravenous maintenance fluid
      therapy. If plasma sodium concentration (p-Na+) declines to levels below 125
      mmol/L in < 48 h, transient or permanent brain damage may occur. There is an
      intense debate as to whether the administered volume (full rate vs. restricted
      rate of infusion) and the composition of solutions used for parenteral
      maintenance fluid therapy (hypotonic vs. isotonic solutions) contribute to the
      development of hyponatremia. So far, there is no definitive pediatric data to
      support a particular choice of parenteral fluid for maintenance therapy in post
      surgical patients. METHODS/DESIGN: Our prospective randomized non-blinded study
      will be conducted in healthy children and adolescents aged 1 to 14 years who have
      been operated for acute appendicitis. Patients will be randomized either to
      intravenous hypotonic (0.23% or 0.40% sodium chloride in glucose, respectively)
      or near-isotonic (0.81% sodium chloride in glucose) solution given at
      approximately three-fourths of the average maintenance rate. The main outcome of
      interest from this study is to evaluate 24 h post-operatively whether differences
      in p-Na+ between treatment groups are large enough to be of clinical relevance.
      In addition, water and electrolyte balance as well as regulatory hormones will be
      measured. DISCUSSION: This study will provide valuable information on the
      efficacy of hypotonic and near-isotonic fluid therapy in preventing a significant
      decrease in p-Na+. Finally, by means of careful electrolyte and water balance and
      by measuring regulatory hormones our results will also contribute to a better
      understanding of the physiopathology of post-operative changes in p-Na+ in a
      population at risk for hyponatremia. TRIAL REGISTRATION: The protocol for this
      study is registered with the current controlled trials registry; registry number:
      ISRCTN43896775.

PMID- 21729309
TI  - Is a HIV vaccine a viable option and at what price? An economic evaluation of
      adding HIV vaccination into existing prevention programs in Thailand.
AB  - BACKGROUND: This study aims to determine the maximum price at which HIV
      vaccination is cost-effective in the Thai healthcare setting. It also aims to
      identify the relative importance of vaccine characteristics and risk behavior
      changes among vaccine recipients to determine how they affect this cost
      effectiveness. METHODS: A semi-Markov model was developed to estimate the costs
      and health outcomes of HIV prevention programs combined with HIV vaccination in
      comparison to the existing HIV prevention programs without vaccination. The
      estimation was based on a lifetime horizon period (99 years) and used the
      government perspective. The analysis focused on both the general population and
      specific high-risk population groups. The maximum price of cost-effective
      vaccination was defined by using threshold analysis; one-way and probabilistic
      sensitivity analyses were performed. The study employed an expected value of
      perfect information (EVPI) analysis to determine the relative importance of
      parameters and to prioritize future studies. RESULTS: The most expensive HIV
      vaccination which is cost-effective when given to the general population was
      12,000 Thai baht (US$1 = 34 Thai baht in 2009). This vaccination came with 70%
      vaccine efficacy and lifetime protection as long as risk behavior was unchanged
      post-vaccination. The vaccine would be considered cost-ineffective at any price
      if it demonstrated low efficacy (30%) and if post-vaccination risk behavior
      increased by 10% or more, especially among the high-risk population groups. The
      incremental cost-effectiveness ratios were the most sensitive to change in post
      vaccination risk behavior, followed by vaccine efficacy and duration of
      protection. The EVPI indicated the need to quantify vaccine efficacy, changed
      post-vaccination risk behavior, and the costs of vaccination programs.
      CONCLUSIONS: The approach used in this study differentiated it from other
      economic evaluations and can be applied for the economic evaluation of other
      health interventions not available in healthcare systems. This study is important
      not only for researchers conducting future HIV vaccine research but also for
      policy decision makers who, in the future, will consider vaccine adoption.

PMID- 21729310
TI  - How can continuing professional development better promote shared decision
      making? Perspectives from an international collaboration.
AB  - BACKGROUND: Shared decision-making is not widely implemented in healthcare. We
      aimed to set a research agenda about promoting shared decision-making through
      continuing professional development. METHODS: Thirty-six participants met for two
      days. RESULTS: Participants suggested ways to improve an environmental scan that
      had inventoried 53 shared decision-making training programs from 14 countries.
      Their proposed research agenda included reaching an international consensus on
      shared decision-making competencies and creating a framework for accrediting
      continuing professional development initiatives in shared decision-making.
      CONCLUSIONS: Variability in shared decision-making training programs showcases
      the need for quality assurance frameworks.

PMID- 21729311
TI  - The receptors for gibbon ape leukemia virus and amphotropic murine leukemia virus
      are not downregulated in productively infected cells.
AB  - BACKGROUND: Over the last several decades it has been noted, using a variety of
      different methods, that cells infected by a specific gammaretrovirus are
      resistant to infection by other retroviruses that employ the same receptor; a
      phenomenon termed receptor interference. Receptor masking is thought to provide
      an earlier means of blocking superinfection, whereas receptor down regulation is
      generally considered to occur in chronically infected cells. RESULTS: We used
      replication-competent GFP-expressing viruses containing either an amphotropic
      murine leukemia virus (A-MLV) or the gibbon ape leukemia virus (GALV) envelope.
      We also constructed similar viruses containing fluorescence-labeled Gag proteins
      for the detection of viral particles. Using this repertoire of reagents together
      with a wide range of antibodies, we were able to determine the presence and
      availability of viral receptors, and detect viral envelope proteins and particles
      presence on the cell surface of chronically infected cells. CONCLUSIONS: A-MLV or
      GALV receptors remain on the surface of chronically infected cells and are
      detectable by respective antibodies, indicating that these receptors are not
      downregulated in these infected cells as previously proposed. We were also able
      to detect viral envelope proteins on the infected cell surface and infected cells
      are unable to bind soluble A-MLV or GALV envelopes indicating that receptor
      binding sites are masked by endogenously expressed A-MLV or GALV viral envelope.
      However, receptor masking does not completely prevent A-MLV or GALV
      superinfection.

PMID- 21729312
TI  - AlignHUSH: alignment of HMMs using structure and hydrophobicity information.
AB  - BACKGROUND: Sensitive remote homology detection and accurate alignments
      especially in the midnight zone of sequence similarity are needed for better
      function annotation and structural modeling of proteins. An algorithm, AlignHUSH
      for HMM-HMM alignment has been developed which is capable of recognizing
      distantly related domain families The method uses structural information, in the
      form of predicted secondary structure probabilities, and hydrophobicity of amino
      acids to align HMMs of two sets of aligned sequences. The effect of using
      adjoining column(s) information has also been investigated and is found to
      increase the sensitivity of HMM-HMM alignments and remote homology detection.
      RESULTS: We have assessed the performance of AlignHUSH using known evolutionary
      relationships available in SCOP. AlignHUSH performs better than the best HMM-HMM
      alignment methods and is observed to be even more sensitive at higher error
      rates. Accuracy of the alignments obtained using AlignHUSH has been assessed
      using the structure-based alignments available in BaliBASE. The alignment length
      and the alignment quality are found to be appropriate for homology modeling and
      function annotation. The alignment accuracy is found to be comparable to existing
      methods for profile-profile alignments. CONCLUSIONS: A new method to align HMMs
      has been developed and is shown to have better sensitivity at error rates of 10%
      and above when compared to other available programs. The proposed method could
      effectively aid obtaining clues to functions of proteins of yet unknown function.
      A web-server incorporating the AlignHUSH method is available at
      http://crick.mbu.iisc.ernet.in/~alignhush/

PMID- 21729313
TI  - Reliability of INTERMED Spanish version and applicability in liver transplant
      patients: a cross-sectional study.
AB  - BACKGROUND: Integrated delivery methods in healthcare systems have been proposed
      to confront the increasing complexity in general health care. INTERMED is an
      empirically derived, observer-rated instrument to measure case complexity. It was
      intended as a visualized, action-oriented decision-support tool for the early
      assessment of bio-psychosocial health risks and health needs. This study aims to
      document the reliability and applicability of the Spanish version of INTERMED in
      liver transplant patients. METHODS: Cross-sectional study of patients who had
      been included in the liver transplant waiting list. Two nurses interviewed the
      patients with INTERMED, and scored the instrument blind to each other. Kappa and
      w-kappa, Spearman, Kendall and intraclass correlation coefficients, and
      Cronbach's alfa were calculated. RESULTS: No patient refused the interview.
      Satisfactory coefficients were documented in most INTERMED items. Kappa was =
      0.858 for the categorization of patients as "complex", and 21 of them (48.8%)
      were classified in this category, and were considered to need integrated
      treatment. CONCLUSIONS: The Spanish version of INTERMED is reliable. Its
      applicability in liver transplant patients adds to its generalizability.

PMID- 21729314
TI  - Multimodality treatment of brain metastases: an institutional survival analysis
      of 275 patients.
AB  - BACKGROUND: Whole brain radiation therapy (WBRT), surgical resection,
      stereotactic radiosurgery (SRS), and combinations of the three modalities are
      used in the management of patients with metastatic brain tumors. We present the
      previously unreported survival outcomes of 275 patients treated for newly
      diagnosed brain metastases at Cancer Care Northwest and Gamma Knife of Spokane
      between 1998 and 2008. METHODS: The effects treatment regimen, age, Eastern
      Cooperative Oncology Group-Performance Status (ECOG-PS), primary tumor histology,
      number of brain metastases, and total volume of brain metastases have on patient
      overall survival were analyzed. Statistical analysis was performed using Kaplan
      Meier survival curves, Andersen 95% confidence intervals, approximate confidence
      intervals for log hazard-ratios, and multivariate Cox proportional hazard models.
      RESULTS: The median clinical follow up time was 7.2 months. On multivariate
      analysis, survival statistically favored patients treated with SRS alone when
      compared to patients treated with WBRT alone (p<0.001), patients treated with
      resection with SRS when compared to patients treated with SRS alone (p=0.020),
      patients in ECOG-PS class 0 when compared to patients in ECOG-PS classes 2
      (p=0.04), 3 (p<0.001), and 4 (p<0.001), patients in the non-small-cell lung
      cancer group when compared to patients in the combined melanoma and renal-cell
      carcinoma group (p<0.001), and patients with breast cancer when compared to
      patients with non-small-cell lung cancer (p<0.001). CONCLUSIONS: In our analysis,
      patients benefited from a combined modality treatment approach and physicians
      must consider patient age, performance status, and primary tumor histology when
      recommending specific treatments regimens.

PMID- 21729315
TI  - Decision quality instrument for treatment of hip and knee osteoarthritis: a
      psychometric evaluation.
AB  - BACKGROUND: A high quality decision requires that patients who meet clinical
      criteria for surgery are informed about the options (including non-surgical
      alternatives) and receive treatments that match their goals. The aim of this
      study was to evaluate the psychometric properties and clinical sensibility of a
      patient self report instrument, to measure the quality of decisions about total
      joint replacement for knee or hip osteoarthritis. METHODS: The performance of the
      Hip/Knee Osteoarthritis Decision Quality Instrument (HK-DQI) was evaluated in two
      samples: (1) a cross-sectional mail survey with 489 patients and 77 providers
      (study 1); and (2) a randomized controlled trial of a patient decision aid with
      138 osteoarthritis patients considering total joint replacement (study 2). The HK
      DQI results in two scores. Knowledge items are summed to create a total knowledge
      score, and a set of goals and concerns are used in a logistic regression model to
      develop a concordance score. The concordance score measures the proportion of
      patients whose treatment matched their goals. Hypotheses related to
      acceptability, feasibility, reliability and validity of the knowledge and
      concordance scores were examined. RESULTS: In study 1, the HK-DQI was completed
      by 382 patients (79%) and 45 providers (58%), and in study 2 by 127 patients
      (92%), with low rates of missing data. The DQI-knowledge score was reproducible
      (ICC = 0.81) and demonstrated discriminant validity (68% decision aid vs. 54%
      control, and 78% providers vs. 61% patients) and content validity. The
      concordance score demonstrated predictive validity, as patients whose treatments
      were concordant with their goals had more confidence and less regret with their
      decision compared to those who did not. CONCLUSIONS: The HK-DQI is feasible and
      acceptable to patients. It can be used to assess whether patients with
      osteoarthritis are making informed decisions about surgery that are concordant
      with their goals.

PMID- 21729316
TI  - Lay perceptions of predictive testing for diabetes based on DNA test results
      versus family history assessment: a focus group study.
AB  - BACKGROUND: This study assessed lay perceptions of issues related to predictive
      genetic testing for multifactorial diseases. These perceived issues may differ
      from the "classic" issues, e.g. autonomy, discrimination, and psychological harm
      that are considered important in predictive testing for monogenic disorders. In
      this study, type 2 diabetes was used as an example, and perceptions with regard
      to predictive testing based on DNA test results and family history assessment
      were compared. METHODS: Eight focus group interviews were held with 45
      individuals aged 35-70 years with (n = 3) and without (n = 1) a family history of
      diabetes, mixed groups of these two (n = 2), and diabetes patients (n = 2). All
      interviews were transcribed and analysed using Atlas-ti. RESULTS: Most
      participants believed in the ability of a predictive test to identify people at
      risk for diabetes and to motivate preventive behaviour. Different reasons
      underlying motivation were considered when comparing DNA test results and a
      family history risk assessment. A perceived drawback of DNA testing was that
      diabetes was considered not severe enough for this type of risk assessment. In
      addition, diabetes family history assessment was not considered useful by some
      participants, since there are also other risk factors involved, not everyone has
      a diabetes family history or knows their family history, and it might have a
      negative influence on family relations. Respect for autonomy of individuals was
      emphasized more with regard to DNA testing than family history assessment. Other
      issues such as psychological harm, discrimination, and privacy were only briefly
      mentioned for both tests. CONCLUSION: The results suggest that most participants
      believe a predictive genetic test could be used in the prevention of
      multifactorial disorders, such as diabetes, but indicate points to consider
      before both these tests are applied. These considerations differ with regard to
      the method of assessment (DNA test or obtaining family history) and also differ
      from monogenic disorders.

PMID- 21729317
TI  - Transcriptomic response of the red tide dinoflagellate, Karenia brevis, to
      nitrogen and phosphorus depletion and addition.
AB  - BACKGROUND: The role of coastal nutrient sources in the persistence of Karenia
      brevis red tides in coastal waters of Florida is a contentious issue that
      warrants investigation into the regulation of nutrient responses in this
      dinoflagellate. In other phytoplankton studied, nutrient status is reflected by
      the expression levels of N- and P-responsive gene transcripts. In
      dinoflagellates, however, many processes are regulated post-transcriptionally.
      All nuclear encoded gene transcripts studied to date possess a 5' trans-spliced
      leader (SL) sequence suggestive, based on the trypanosome model, of post
      transcriptional regulation. The current study therefore sought to determine if
      the transcriptome of K. brevis is responsive to nitrogen and phosphorus and is
      informative of nutrient status. RESULTS: Microarray analysis of N-depleted K.
      brevis cultures revealed an increase in the expression of transcripts involved in
      N-assimilation (nitrate and ammonium transporters, glutamine synthetases)
      relative to nutrient replete cells. In contrast, a transcriptional signal of P
      starvation was not apparent despite evidence of P-starvation based on their rapid
      growth response to P-addition. To study transcriptome responses to nutrient
      addition, the limiting nutrient was added to depleted cells and changes in global
      gene expression were assessed over the first 48 hours following nutrient
      addition. Both N- and P-addition resulted in significant changes in approximately
      4% of genes on the microarray, using a significance cutoff of 1.7-fold and p <=
      10-4. By far, the earliest responding genes were dominated in both nutrient
      treatments by pentatricopeptide repeat (PPR) proteins, which increased in
      expression up to 3-fold by 1 h following nutrient addition. PPR proteins are
      nuclear encoded proteins involved in chloroplast and mitochondria RNA processing.
      Correspondingly, other functions enriched in response to both nutrients were
      photosystem and ribosomal genes. CONCLUSIONS: Microarray analysis provided
      transcriptomic evidence for N- but not P-limitation in K. brevis. Transcriptomic
      responses to the addition of either N or P suggest a concerted program leading to
      the reactivation of chloroplast functions. Even the earliest responding PPR
      protein transcripts possess a 5' SL sequence that suggests post-transcriptional
      control. Given the current state of knowledge of dinoflagellate gene regulation,
      it is currently unclear how these rapid changes in such transcript levels are
      achieved.

PMID- 21729318
TI  - Continuity and change in human resources policies for health: lessons from
      Brazil.
AB  - BACKGROUND: This paper reports on progress in implementing human resources for
      health (HRH) policies in Brazil, in the context of the implementation and
      expansion of the Unified Health System (Sistema Unico de Saude - SUS).The three
      main objectives were: i) to reconstruct the chronology of long term HRH change in
      Brazil, and to identify and discuss the precursors, drivers, and enablers for
      these changes over a long time period; (ii) to examine how change was achieved by
      describing facilitators and constraints, and how policies were adapted to deal
      with the latter; and (iii) to report on the current situation and draw policy
      implications. METHODS: A mixed methods approach was used. A literature review was
      conducted using pre-defined keywords; and stakeholders were contacted and asked
      to provide relevant information, data and policy reports. RESULTS: There are two
      key features of HRH change which are related to the implementation of SUS which
      merit attention: the achievement of staffing growth, and the improvement in HRH
      policy making and management. Staff growth rates across the period have been high
      enough to exceed population growth rates. As a consequence, the ratio of staff to
      population has improved. In 1990 the physician ratio per 1000 inhabitants was
      1.12. In 2007, it was 1.74. Another critical factor in achieving staffing growth
      has been HRH policy making capacity and influence within the political
      establishment. CONCLUSIONS: Policies have had to adapt to changing circumstances,
      whilst focusing on sequential improvements aimed at achieving long term goals.
      The end objectives, of improving care and access to care, have been kept in view.
      No one Ministry could secure all the resources and impetus for change that has
      been required, hence the need for inter-ministry, inter-governmental and inter
      agency collaboration, and the development of alliances of shared interest. Across
      the period of thirty years or more, not all initiatives have been equally
      successful, but a momentum has been maintained. There was no single long term
      plan or strategy, but in Brazil this has enabled the progress to be adapted and
      re-oriented as the broader context changed over the years.

PMID- 21729320
TI  - Failure to detect tuberculosis in Black lechwe antelopes (Kobus leche smithemani)
      in Zambia.
AB  - BACKGROUND: Two types of lechwe antelopes exclusively exist in their natural
      ecosystems in Zambia; the Black lechwe (Kobus leche smithemani) and the Kafue
      lechwe (Kobus leche kafuensis). Despite inhabiting similar ecosystems,
      tuberculosis has been reported in Kafue lechwe without its documentation in Black
      lechwe antelopes. However, the past few decades have seen a drastic decline in
      both lechwe populations. Whereas studies have postulated that infectious diseases
      such as tuberculosis are having a negative impact on the Kafue lechwe population,
      no information is available on Black lechwe antelopes. Thus this study was
      conducted to investigate tuberculosis in Black lechwe antelopes of the Bangweulu
      swamps in comparison with the Kafue lechwe antelopes of Lochinvar. FINDINGS: A
      total of 44 lechwe antelopes (Black (n = 30): Kafue (n = 14) were sampled from
      Bangweulu and Lochinvar respectively. A positive case was defined with findings
      of gross lesions with Ziehl Nielsen and culture confirmation. Out of the 14
      animals examined in Lochinvar, 21.4% [95% CI: 15.4, 44.4%] had necropsy lesions
      consistent with tuberculosis. The corresponding samples from 30 Black lechwe of
      Bangweulu yielded negative results on all the three tests. CONCLUSIONS: Current
      findings from this study intimate the possible absence of tuberculosis in Black
      lechwe antelopes whilst confirming the presence of tuberculosis in Kafue lechwe
      of the Kafue basin. The absence of tuberculosis in the Black lechwe suggests that
      the observed population decline may not be caused by tuberculosis. However,
      without detailed molecular epidemiological studies it is not possible to
      determine the association of M. bovis infection in sympatric animal populations.
      The possible role of transmission of tuberculosis between wildlife and cattle is
      discussed herein. Findings.

PMID- 21729319
TI  - Targeting insulin-like growth factor axis in hepatocellular carcinoma.
AB  - The insulin-like growth factor (IGF) axis contains ligands, receptors,
      substrates, and ligand binding proteins. The essential role of IGF axis in
      hepatocellular carcinoma (HCC) has been illustrated in HCC cell lines and in
      animal xenograft models. Preclinical evidence provides ample indication that all
      four components of IGF axis are crucial in the carcinogenic and metastatic
      potential of HCC. Several strategies targeting this system including monoclonal
      antibodies against the IGF 1 receptor (IGF-1R) and small molecule inhibitors of
      the tyrosine kinase function of IGF-1R are under active investigation. This
      review describes the most up-to-date understanding of this complex axis in HCC,
      and provides relevant information on clinical trials targeting the IGF axis in
      HCC with a focus on anti-IGF-1R approach. IGF axis is increasingly recognized as
      one of the most relevant pathways in HCC and agents targeting this axis can
      potentially play an important role in the treatment of HCC.

PMID- 21729321
TI  - The oncofetal gene survivin is re-expressed in osteoarthritis and is required for
      chondrocyte proliferation in vitro.
AB  - BACKGROUND: Regulation of cell death and cell division are key processes during
      chondrogenesis and in cartilage homeostasis and pathology. The oncogene survivin
      is considered to be critical for the coordination of mitosis and maintenance of
      cell viability during embryonic development and in cancer, and is not detectable
      in most adult differentiated tissues and cells. We analyzed survivin expression
      in osteoarthritic cartilage and its function in primary human chondrocytes in
      vitro. METHODS: Survivin expression was analyzed by immunoblotting and
      quantitative real-time PCR. The localization was visualized by
      immunofluorescence. Survivin functions in vitro were investigated by transfection
      of a specific siRNA. RESULTS: Survivin was expressed in human osteoarthritic
      cartilage, but was not detectable in macroscopically and microscopically
      unaffected cartilage of osteoarthritic knee joints. In primary human chondrocyte
      cultures, survivin was localized to heterogeneous subcellular compartments.
      Suppression of survivin resulted in inhibition of cell cycle progression and
      sensitization toward apoptotic stimuli in vitro. CONCLUSIONS: The present study
      indicates a role for survivin in osteoarthritic cartilage and human chondrocytes.
      In vitro experiments indicated its involvement in cellular division and
      viability. Learning more about the functions of survivin in chondrocyte biology
      might further help toward understanding and modulating the complex processes of
      cartilage pathology and regeneration.

PMID- 21729322
TI  - Parent satisfaction with a pediatric practice in Germany: a questionnaire-based
      study.
AB  - BACKGROUND: Parental satisfaction with a pediatric day center is essential for
      the medical treatment of children, since it is closely related to compliance. In
      order to ascertain factors which predict parental satisfaction as well as to
      discover possible weak points, we developed a questionnaire. METHODS: 127 parents
      visiting the pediatric day center from October to November 2010 were asked to
      respond to a questionnaire. The survey was given to them directly by the doctor
      after their visit and it provided the opportunity to determine subjective and
      soft factors in quality management, which is essential for a pediatric practice.
      The questionnaire consisted of 27 items divided into three scales. The scales
      were as follows: satisfaction concerning the infrastructure and organization,
      satisfaction concerning the communicative and empathic competence of the doctor
      as well as the other staff, and finally the results and the overall impression.
      Moreover, the survey asked the respondents for their comments on the pediatric
      day center and sociodemographic data were queried. RESULTS: A total of 67 parents
      (52,7%) responded to the survey. The mean parental satisfaction concerning
      infrastructure and organization achieved 3,61 (scale 1-very unsatisfied--through
      4-very satisfied). The mean satisfaction with the expertise of the doctor and the
      staff was 3,56 and the overall satisfaction was 3,65. Ninety-one percent of the
      parents would visit the pediatric practice again and 84,2% would definitely
      recommend the practice to others. CONCLUSION: Surveys on parental satisfaction
      are essential for the success of a pediatric day center. Apart from the doctors
      abilities to interact with the parents, other factors, such as a short waiting
      period, a friendly and helpful staff, as well as appealing premises are essential
      for a high overall level of satisfaction.

PMID- 21729323
TI  - Exome-wide DNA capture and next generation sequencing in domestic and wild
      species.
AB  - BACKGROUND: Gene-targeted and genome-wide markers are crucial to advance
      evolutionary biology, agriculture, and biodiversity conservation by improving our
      understanding of genetic processes underlying adaptation and speciation.
      Unfortunately, for eukaryotic species with large genomes it remains costly to
      obtain genome sequences and to develop genome resources such as genome-wide SNPs.
      A method is needed to allow gene-targeted, next-generation sequencing that is
      flexible enough to include any gene or number of genes, unlike transcriptome
      sequencing. Such a method would allow sequencing of many individuals, avoiding
      ascertainment bias in subsequent population genetic analyses.We demonstrate the
      usefulness of a recent technology, exon capture, for genome-wide, gene-targeted
      marker discovery in species with no genome resources. We use coding gene
      sequences from the domestic cow genome sequence (Bos taurus) to capture (enrich
      for), and subsequently sequence, thousands of exons of B. taurus, B. indicus, and
      Bison bison (wild bison). Our capture array has probes for 16,131 exons in 2,570
      genes, including 203 candidate genes with known function and of interest for
      their association with disease and other fitness traits. RESULTS: We successfully
      sequenced and mapped exon sequences from across the 29 autosomes and X chromosome
      in the B. taurus genome sequence. Exon capture and high-throughput sequencing
      identified thousands of putative SNPs spread evenly across all reference
      chromosomes, in all three individuals, including hundreds of SNPs in our targeted
      candidate genes. CONCLUSIONS: This study shows exon capture can be customized for
      SNP discovery in many individuals and for non-model species without genomic
      resources. Our captured exome subset was small enough for affordable next
      generation sequencing, and successfully captured exons from a divergent wild
      species using the domestic cow genome as reference.

PMID- 21729324
TI  - Quantitative characterization and analysis of the dynamic NF-kappaB response in
      microglia.
AB  - BACKGROUND: Activation of the NF-kappaB transcription factor and its associated
      gene expression in microglia is a key component in the response to brain injury.
      Its activation is dynamic and is part of a network of biochemical species with
      multiple feedback regulatory mechanisms. Mathematical modeling, which has been
      instrumental for understanding the NF-kappaB response in other cell types, offers
      a valuable tool to investigate the regulation of NF-kappaB activation in
      microglia at a systems level. RESULTS: We quantify the dynamic response of NF
      kappaB activation and activation of the upstream kinase IKK using ELISA
      measurements of a microglial cell line following treatment with the pro
      inflammatory cytokine TNFalpha. A new mathematical model is developed based on
      these data sets using a modular procedure that exploits the feedback structure of
      the network. We show that the new model requires previously unmodeled dynamics
      involved in the stimulus-induced degradation of the inhibitor IkappaBalpha in
      order to properly describe microglial NF-kappaB activation in a statistically
      consistent manner. This suggests a more prominent role for the ubiquitin
      proteasome system in regulating the activation of NF-kappaB to inflammatory
      stimuli. We also find that the introduction of nonlinearities in the kinetics of
      IKK activation and inactivation is essential for proper characterization of
      transient IKK activity and corresponds to known biological mechanisms. Numerical
      analyses of the model highlight key regulators of the microglial NF-kappaB
      response, as well as those governing IKK activation. Results illustrate the
      dynamic regulatory mechanisms and the robust yet fragile nature of the negative
      feedback regulated network. CONCLUSIONS: We have developed a new mathematical
      model that incorporates previously unmodeled dynamics to characterize the dynamic
      response of the NF-kappaB signaling network in microglia. This model is the first
      of its kind for microglia and provides a tool for the quantitative, systems level
      study the dynamic cellular response to inflammatory stimuli.

PMID- 21729325
TI  - High sensitive troponin T and heart fatty acid binding protein: novel biomarker
      in heart failure with normal ejection fraction? A cross-sectional study.
AB  - BACKGROUND: High sensitive troponin T (hsTnT) and heart fatty acid binding
      protein (hFABP) are both markers of myocardial injury and predict adverse outcome
      in patients with systolic heart failure (SHF). We tested whether hsTnT and hFABP
      plasma levels are elevated in patients with heart failure with normal ejection
      fraction (HFnEF). METHODS: We analyzed hsTnT, hFABP and N-terminal brain
      natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients
      with asymptomatic left ventricular diastolic dysfunction (LVDD), and 30 controls
      with normal diastolic function. Patients were classified to have HFnEF when the
      diagnostic criteria as recommended by the European Society of Cardiology were
      met. RESULTS: Levels of hs TnT and hFABP were significantly higher in patients
      with asymptomatic LVDD and HFnEF (both p < 0.001) compared to controls. The hsTnT
      levels were 5.6 [0.0-9.8] pg/ml in LVDD vs. 8.5 [3.9-17.5] pg/ml in HFnEF vs.
      <0.03 [< 0.03-6.4] pg/ml in controls; hFABP levels were 3029 [2533-3761] pg/ml in
      LVDD vs. 3669 [2918-4839] pg/ml in HFnEF vs. 2361 [1860-3081] pg/ml in controls.
      Furthermore, hsTnT and hFABP levels were higher in subjects with HFnEF compared
      to LVDD (p = 0.015 and p = 0.022). CONCLUSION: In HFnEF patients, hsTnT and hFABP
      are elevated independent of coronary artery disease, suggesting that ongoing
      myocardial damage plays a critical role in the pathophysiology. A combination of
      biomarkers and echocardiographic parameters might improve diagnostic accuracy and
      risk stratification of patients with HFnEF.

PMID- 21729326
TI  - An organotypic slice culture model of chronic white matter injury with maturation
      arrest of oligodendrocyte progenitors.
AB  - BACKGROUND: CNS myelination disturbances commonly occur in chronic white matter
      lesions in neurodevelopmental and adult neurological disorders. Recent studies
      support that myelination failure can involve a disrupted cellular repair
      mechanism where oligodendrocyte (OL) progenitor cells (OPCs) proliferate in
      lesions with diffuse astrogliosis, but fail to fully differentiate to mature
      myelinating OLs. There are no in vitro models that reproduce these features of
      myelination failure. RESULTS: Forebrain coronal slices from postnatal day (P)
      0.5/1 rat pups were cultured for 1, 5, or 9 days in vitro (DIV). Slices rapidly
      exhibited diffuse astrogliosis and accumulation of the extracellular matrix
      glycosaminoglycan hyaluronan (HA), an inhibitor of OPC differentiation and re
      myelination. At 1 DIV ~1.5% of Olig2+ OLs displayed caspase-3 activation, which
      increased to ~11.5% by 9 DIV. At 1 DIV the density of PDGFRalpha+ and
      PDGFRalpha+/Ki67+ OPCs were significantly elevated compared to 0 DIV (P < 0.01).
      Despite this proliferative response, at 9 DIV ~60% of white matter OLs were late
      progenitors (preOLs), compared to ~7% in the postnatal day 10 rat (P < 0.0001),
      consistent with preOL maturation arrest. Addition of HA to slices significantly
      decreased the density of MBP+ OLs at 9 DIV compared to controls (217 +/- 16 vs.
      328 +/- 17 cells/mm2, respectively; P = 0.0003), supporting an inhibitory role of
      HA in OL lineage progression in chronic lesions. CONCLUSIONS: Diffuse white
      matter astrogliosis and early OPC proliferation with impaired OL maturation were
      reproduced in this model of myelination failure. This system may be used to
      define mechanisms of OPC maturation arrest and myelination failure related to
      astrogliosis and HA accumulation.

PMID- 21729327
TI  - Beta-amyloid increases the expression level of ATBF1 responsible for death in
      cultured cortical neurons.
AB  - BACKGROUND: Recently, several lines of evidence have shown the aberrant
      expression of cell-cycle-related proteins and tumor suppressor proteins in
      vulnerable neurons of the Alzheimer's disease (AD) brain and transgenic mouse
      models of AD; these proteins are associated with various paradigms of neuronal
      death. It has been reported that ATBF1 induces cell cycle arrest associated with
      neuronal differentiation in the developing rat brain, and that gene is one of the
      candidate tumor suppressor genes for prostate and breast cancers in whose cells
      overexpressed ATBF1 induces cell cycle arrest. However, the involvement of ATBF1
      in AD pathogenesis is as yet unknown. RESULTS: We found that ATBF1 was up
      regulated in the brains of 17-month-old Tg2576 mice compared with those of age
      matched wild-type mice. Moreover, our in vitro studies showed that Abeta1-42 and
      DNA-damaging drugs, namely, etoposide and homocysteine, increased the expression
      ATBF1 level in primary rat cortical neurons, whereas the knockdown of ATBF1 in
      these neurons protected against neuronal death induced by Abeta1-42, etoposide,
      and homocysteine, indicating that ATBF1 mediates neuronal death in response to
      these substances. In addition, we found that ATBF1-mediated neuronal death is
      dependent on ataxia-telangiectasia mutated (ATM) because the blockage of ATM
      activity by treatment with ATM inhibitors, caffeine and KU55933, abolished ATBF1
      function in neuronal death. Furthermore, Abeta1-42 phosphorylates ATM, and ATBF1
      interacts with phosphorylated ATM. CONCLUSIONS: To the best of our knowledge,
      this is the first report that Abeta1-42 and DNA-damaging drugs increased the
      ATBF1 expression level in primary rat cortical neurons; this increase, in turn,
      may activate ATM signaling responsible for neuronal death through the binding of
      ATBF1 to phosphorylated ATM. ATBF1 may therefore be a suitable target for
      therapeutic intervention of AD.

PMID- 21729328
TI  - Identification of two linear B-cell epitopes from West Nile virus NS1 by
      screening a phage-displayed random peptide library.
AB  - BACKGROUND: The West Nile virus (WNV) nonstructural protein 1 (NS1) is an
      important antigenic protein that elicits protective antibody responses in animals
      and can be used for the serological diagnosis of WNV infection. Although previous
      work has demonstrated the vital role of WNV NS1-specific antibody responses, the
      specific epitopes in the NS1 have not been identified. RESULTS: The present study
      describes the identification of two linear B-cell epitopes in WNV NS1 through
      screening a phage-displayed random 12-mer peptide library with two monoclonal
      antibodies (mAbs) 3C7 and 4D1 that directed against the NS1. The mAbs 3C7 and 4D1
      recognized phages displaying peptides with the consensus motifs LTATTEK and
      VVDGPETKEC, respectively. Exact sequences of both motifs were found in the NS1
      ((895)LTATTEK(901) and (925)VVDGPETKEC(934)). Further identification of the
      displayed B cell epitopes were conducted using a set of truncated peptides
      expressed as MBP fusion proteins. The data indicated that (896)TATTEK(901) and
      (925)VVDGPETKEC(934) are minimal determinants of the linear B cell epitopes
      recognized by the mAbs 3C7 and 4D1, respectively. Antibodies present in the serum
      of WNV-positive horses recognized the minimal linear epitopes in Western blot
      analysis, indicating that the two peptides are antigenic in horses during
      infection. Furthermore, we found that the epitope recognized by 3C7 is conserved
      only among WNV strains, whereas the epitope recognized by 4D1 is a common motif
      shared among WNV and other members of Japanese encephalitis virus (JEV)
      serocomplex. CONCLUSIONS: We identified TATTEK and VVDGPETKEC as NS1-specific
      linear B-cell epitopes recognized by the mAbs 3C7 and 4D1, respectively. The
      knowledge and reagents generated in this study may have potential applications in
      differential diagnosis and the development of epitope-based marker vaccines
      against WNV and other viruses of JEV serocomplex.

PMID- 21729329
TI  - Patients' age as a determinant of care received following acute stroke: a
      systematic review.
AB  - BACKGROUND: Evidence-based care should improve acute stroke outcomes with the
      same magnitude of effect for stroke patients of all ages. However, there is
      evidence to suggest that, in some instances, older stroke patients may receive
      poorer quality care than younger patients.Our aim was to systematically review
      evidence of the quality of care provided to patients with acute stroke related to
      their age. Quality of care was determined by compliance with recommended care
      processes. METHODS: We systematically searched MEDLINE, CINAHL, ISI Web of
      Knowledge, Ageline and the Cochrane Library databases to identify publications
      (1995-2009) that reported data on acute stroke care process indicators by patient
      age. Data extracted included patient demographics and process indicator
      compliance. Included publications were critically appraised by two independent
      reviewers using the Critical Appraisal Skills Programme tool, and a comparison
      was made of the risk of bias according to studies' findings. The evidence base
      for reported process indicators was determined, and meta-analysis was undertaken
      for studies with sufficient similarity. RESULTS: Nine from 163 potential studies
      met the inclusion criteria. Of the 56 process indicators reported, eleven
      indicators were evidence-based. Seven of these indicators (64%) showed
      significantly poorer care for older patients compared to younger ones, while
      younger patients received comparatively inferior care for only antihypertensive
      therapy at discharge. Our findings are limited by the variable methodological
      quality of included studies. CONCLUSION: Patients' age may be a factor in the
      care they receive after an acute stroke. However, the possible influence of
      patients' age on clinicians' decision-making must be considered in terms of the
      many complex issues that surround the provision of optimal care for older
      patients with acute stroke.

PMID- 21729330
TI  - HuR binding to AU-rich elements present in the 3' untranslated region of
      Classical swine fever virus.
AB  - BACKGROUND: Classical swine fever virus (CSFV) is the member of the genus
      Pestivirus under the family Flaviviridae. The 5' untranslated region (UTR) of
      CSFV contains the IRES, which is a highly structured element that recruits the
      translation machinery. The 3' UTR is usually the recognition site of the viral
      replicase to initiate minus-strand RNA synthesis. Adenosine-uridine rich elements
      (ARE) are instability determinants present in the 3' UTR of short-lived mRNAs.
      However, the presence of AREs in the 3' UTR of CSFV conserved in all known
      strains has never been reported. This study inspects a possible role of the ARE
      in the 3' UTR of CSFV. RESULTS: Using RNA pull-down and LC/MS/MS assays, this
      study identified at least 32 possible host factors derived from the cytoplasmic
      extracts of PK-15 cells that bind to the CSFV 3' UTR, one of which is HuR. HuR is
      known to bind the AREs and protect the mRNA from degradation. Using recombinant
      GST-HuR, this study demonstrates that HuR binds to the ARE present in the 3' UTR
      of CSFV in vitro and that the binding ability is conserved in strains
      irrespective of virulence. CONCLUSIONS: This study identified one of the CSFV 3'
      UTR binding proteins HuR is specifically binding to in the ARE region.

PMID- 21729331
TI  - Isolation of mouse mesenchymal stem cells with normal ploidy from bone marrows by
      reducing oxidative stress in combination with extracellular matrix.
AB  - BACKGROUND: Isolation of mouse MSCs (mMSCs) with normal ploidy from bone marrow
      remains challenging. mMSCs isolated under 20% O(2) are frequently contaminated by
      overgrown hematopoietic cells, and could also be especially vulnerable to
      oxidative damage, resulting in chromosomal instability. Culture under low oxygen
      or extracellular matrix (ECM) improves proliferation of MSCs in several species.
      We tested the hypothesis that culture under low oxygen in combination with ECM
      prepared from mouse embryonic fibroblast (MEF-ECM) could be used to purify
      proliferative mMSCs, and to reduce oxidative damage and maintain their
      chromosomal stability. RESULTS: Optimization of culture conditions under 20% O(2)
      resulted in immortalization of mMSCs, showing extensive chromosome abnormalities,
      consistent with previous studies. In contrast, culture under low oxygen (2% O(2))
      improved proliferation of mMSCs and reduced oxidative damage, such that mMSCs
      were purified simply by plating at low density under 2% O(2). MEF-ECM reduced
      oxidative damage and enhanced proliferation of mMSCs. However, these isolated
      mMSCs still exhibited high frequency of chromosome abnormalities, suggesting that
      low oxygen or in combination with MEF-ECM was insufficient to fully protect mMSCs
      from oxidative damage. Notably, antioxidants (alpha -phenyl-t-butyl nitrone (PBN)
      and N-acetylcysteine (NAC)) further reduced DNA damage and chromosomal
      abnormalities, and increased proliferation of mMSCs. mMSCs isolated by the
      combination method were successfully used to generate induced pluripotent stem
      (iPS) cells by ectopic expression of Oct4, Sox2, Klf4 and c-Myc. CONCLUSIONS: We
      have developed a technique that allows to reduce the number of karyotypic
      abnormalities for isolation of primary mMSCs and for limited culture period by
      combination of low oxygen, MEF-ECM, antioxidants and low density plating
      strategy. The effectiveness of the new combination method is demonstrated by
      successful generation of iPS cells from the isolated mMSCs. However, a culture
      system for mMSCs still is needed to prevent all the anomalies, especially after a
      long-term culture period.

PMID- 21729332
TI  - Epidemiological characteristics and predictors of late presentation of HIV
      infection in Barcelona (Spain) during the period 2001-2009.
AB  - BACKGROUND: Early diagnosis of HIV infection can prevent morbidity and mortality
      as well as reduce HIV transmission. The aim of the present study was to assess
      prevalence, describe trends and identify factors associated with late
      presentation of HIV infection in Barcelona (Spain) during the period 2001-09.
      METHODS: Demographic and epidemiological characteristics of cases reported to the
      Barcelona HIV surveillance system were analysed. Late presentation was defined
      for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or
      diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic
      regression were used to identify predictors of late presentation. RESULTS: Of the
      2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4
      cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507
      studied cases over these nine years were late presenters varying from 48% among
      men who have sex with men to 70% among heterosexual men. The proportion of late
      presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and
      52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and
      2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent
      risk factors for late presentation were older age at diagnosis (p < 0.0001), use
      of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and
      being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002).
      CONCLUSION: Late presentation of HIV is still too frequent in all transmission
      groups in spite of a strong commitment with HIV prevention in our city. It is
      necessary to develop interventions that increase HIV testing and facilitate
      earlier entry into HIV care.

PMID- 21729333
TI  - Structural and functional basis for RNA cleavage by Ire1.
AB  - BACKGROUND: The unfolded protein response (UPR) controls the protein folding
      capacity of the endoplasmic reticulum (ER). Central to this signaling pathway is
      the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The
      endoribonuclease (RNase) domain of Ire1 initiates a non-conventional mRNA
      splicing reaction, leading to the production of a transcription factor that
      controls UPR target genes. The mRNA splicing reaction is an obligatory step of
      Ire1 signaling, yet its mechanism has remained poorly understood due to the
      absence of substrate-bound crystal structures of Ire1, the lack of structural
      similarity between Ire1 and other RNases, and a scarcity of quantitative
      enzymological data. Here, we experimentally define the active site of Ire1 RNase
      and quantitatively evaluate the contribution of the key active site residues to
      catalysis. RESULTS: This analysis and two new crystal structures suggest that
      Ire1 RNase uses histidine H1061 and tyrosine Y1043 as the general acid-general
      base pair contributing >=7.6 kcal/mol and 1.4 kcal/mol to transition state
      stabilization, respectively, and asparagine N1057 and arginine R1056 for
      coordination of the scissile phosphate. Investigation of the stem-loop
      recognition revealed that additionally to the stem-loops derived from the classic
      Ire1 substrates HAC1 and Xbp1 mRNA, Ire1 can site-specifically and rapidly cleave
      anticodon stem-loop (ASL) of unmodified tRNAPhe, extending known substrate
      specificity of Ire1 RNase. CONCLUSIONS: Our data define the catalytic center of
      Ire1 RNase and suggest a mechanism of RNA cleavage: each RNase monomer apparently
      contains a separate catalytic apparatus for RNA cleavage, whereas two RNase
      subunits contribute to RNA stem-loop docking. Conservation of the key residues
      among Ire1 homologues suggests that the mechanism elucidated here for yeast Ire1
      applies to Ire1 in metazoan cells, and to the only known Ire1 homologue RNase L.

PMID- 21729334
TI  - Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1.
AB  - BACKGROUND: Ire1 is a signal transduction protein in the endoplasmic reticulum
      (ER) membrane that serves to adjust the protein-folding capacity of the ER
      according to the needs of the cell. Ire1 signals, in a transcriptional program,
      the unfolded protein response (UPR) via the coordinated action of its protein
      kinase and RNase domains. In this study, we investigated how the binding of
      cofactors to the kinase domain of Ire1 modulates its RNase activity. RESULTS: Our
      results suggest that the kinase domain of Ire1 initially binds cofactors without
      activation of the RNase domain. RNase is activated upon a subsequent
      conformational rearrangement of Ire1 governed by the chemical properties of bound
      cofactors. The conformational step can be selectively inhibited by chemical
      perturbations of cofactors. Substitution of a single oxygen atom in the terminal
      beta-phosphate group of a potent cofactor ADP by sulfur results in ADPbetaS, a
      cofactor that binds to Ire1 as well as to ADP but does not activate RNase. RNase
      activity can be rescued by thiophilic metal ions such as Mn2+ and Cd2+, revealing
      a functional metal ion-phosphate interaction which controls the conformation and
      RNase activity of the Ire1 ADP complex. Mutagenesis of the kinase domain suggests
      that this rearrangement involves movement of the alphaC-helix, which is generally
      conserved among protein kinases. Using X-ray crystallography, we show that
      oligomerization of Ire1 is sufficient for placing the alphaC-helix in the active,
      cofactor-bound-like conformation, even in the absence of cofactors. CONCLUSIONS:
      Our structural and biochemical evidence converges on a model that the cofactor
      induced conformational change in Ire1 is coupled to oligomerization of the
      receptor, which, in turn, activates RNase. The data reveal that cofactor-Ire1
      interactions occur in two independent steps: binding of a cofactor to Ire1 and
      subsequent rearrangement of Ire1 resulting in its self-association. The
      pronounced allosteric effect of cofactors on protein-protein interactions
      involving Ire1's kinase domain suggests that protein kinases and pseudokinases
      encoded in metazoan genomes may use ATP pocket-binding ligands similarly to exert
      signaling roles other than phosphoryl transfer.

PMID- 21729335
TI  - Autism.
AB  - INTRODUCTION: Evidence for the efficacy of treatments for autism has improved in
      recent years. In this systematic review the evidence for both drug and non-drug
      treatments is appraised and clinical guidance is provided for their use. METHODS
      AND OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of early intensive multidisciplinary
      intervention programmes in children with autism? What are the effects of dietary
      interventions in children with autism? What are the effects of drug treatments in
      children with autism? What are the effects of non-drug treatments in children
      with autism? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to May 2009 (Clinical evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 30 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: applied behavioural analysis; auditory
      integration training; Autism Preschool Programme; casein-free diet; chelation;
      Child's Talk programme; cognitive behavioural therapy; digestive enzymes;
      EarlyBird programme; facilitated communication; Floortime therapy; gluten-free
      diet; immunoglobulins; melatonin; memantine; methylphenidate; More Than Words
      programme; music therapy; olanzapine; omega-3 fish oil; picture exchange
      communication system; Portage scheme; probiotics; relationship development
      interventions; risperidone; secretin; selective serotonin reuptake inhibitors
      (SSRIs); sensory integration training; social stories; social skills training;
      Son-Rise programme; TEACCH; vitamin A; vitamin B6 (pyridoxine) plus magnesium;
      and vitamin C.

PMID- 21729336
TI  - Colic in infants.
AB  - INTRODUCTION: Colic in infants causes one in six families (17%) with children to
      consult a health professional. One systematic review of 15 community-based
      studies found a wide variation in prevalence, which depended on study design and
      method of recording. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical question: What are the effects of
      treatments for colic in infants? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to September 2009 (Clinical Evidence
      reviews are updated periodically, please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 27
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: advice
      to increase carrying, advice to reduce stimulation, casein hydrolysate milk,
      cranial osteopathy, crib vibrator device, focused counselling, gripe water,
      infant massage, low-lactose milk, simethicone, soya-based infant feeds, spinal
      manipulation, and whey hydrolysate milk.

PMID- 21729337
TI  - Impacted wisdom teeth.
AB  - INTRODUCTION: The incidence of impacted wisdom teeth is high, with some 72% of
      Swedish people aged 20 to 30 years having at least one impacted third molar.
      Impacted wisdom teeth occur because of a lack of space, obstruction, or abnormal
      position, and can cause inflammatory dental disease manifested by pain and
      swelling of infected teeth and may destroy adjacent teeth and bone. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: Should asymptomatic and disease-free impacted wisdom teeth be
      removed prophylactically? What are the effects of different surgical methods of
      removing impacted wisdom teeth? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to July 2009 (Clinical Evidence reviews
      are updated periodically, please check our website for the most up-to-date
      version of this review). We included harms alerts from relevant organisations
      such as the US Food and Drug Administration (FDA) and the UK Medicines and
      Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of
      the quality of evidence for interventions. RESULTS: We found 25 systematic
      reviews, RCTs, or observational studies that met our inclusion criteria.
      CONCLUSIONS: In this systematic review we present information relating to the
      effectiveness and safety of the following interventions: prophylactic extraction,
      active surveillance, and different surgical methods of removing impacted wisdom
      teeth.

PMID- 21729338
TI  - Pancreatic cancer.
AB  - INTRODUCTION: Pancreatic cancer is the fourth most common cause of cancer death
      in higher-income countries, with 5-year survival only 10% even in people
      presenting with early-stage cancer. Risk factors include smoking, high alcohol
      intake, and dietary factors, while diabetes mellitus and previous pancreatitis
      may also increase the risk. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical questions: What are the effects
      of surgical treatments in people with pancreatic cancer considered suitable for
      complete tumour resection? What are the effects of interventions to prevent
      pancreatic leak after pancreaticoduodenectomy in people with pancreatic cancer
      considered suitable for complete tumour resection? What are the effects of
      adjuvant treatments in people with completely resected pancreatic cancer? What
      are the effects of interventions in people with non-resectable (locally advanced
      or advanced) pancreatic cancer? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to August 2009 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 46
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions:
      chemoradiotherapy; chemoradiotherapy for non-resectable pancreatic cancer;
      chemoradiotherapy for resected pancreatic cancer; fibrin glue; fluorouracil-based
      chemotherapy (adjuvant) for resected pancreatic cancer (with or without surgery);
      fluorouracil-based chemotherapy for non-resectable pancreatic cancer;
      fluorouracil-based chemotherapy (systemic); fluorouracil-based combination
      chemotherapy; fluorouracil-based monotherapy for non-resectable pancreatic
      cancer; gemcitabine-based chemotherapy (adjuvant) for resected pancreatic cancer;
      gemcitabine-based chemotherapy (systemic); gemcitabine-based combination
      chemotherapy; gemcitabine-based monotherapy for non-resectable pancreatic cancer;
      lymphadenectomy (extended [radical], or standard) in people having
      pancreaticoduodenectomy; pancreatic duct occlusion; pancreaticoduodenectomy
      (pylorus-preserving); pancreaticoduodenectomy (Whipple's procedure);
      pancreaticogastrostomy reconstruction; pancreaticojejunostomy; and somatostatin
      and somatostatin analogues.

PMID- 21729339
TI  - Comparison of experiences of stress and coping between young people at risk of
      psychosis and a non-clinical cohort.
AB  - BACKGROUND: Although the experience of stress and associated coping responses are
      thought to play a role in the onset of schizophrenia and other psychotic
      disorders, there is little empirical evidence to support such a relationship. The
      relatively recent development of validated and reliable criteria for identifying
      young people at "ultra" high-risk (UHR) of psychosis has enabled the process of
      illness onset to be studied more closely than was previously possible. METHOD:
      This longitudinal study compared the experiences of stress and coping between a
      UHR cohort (N=143) and a healthy comparison group (HC group, N=32). RESULTS: The
      UHR group experienced significantly fewer life events over a 12-month period than
      the HC group, but there was no difference in the experience of minor events or
      "hassles". However, the UHR group reported feeling significantly more distressed
      by events, felt they coped more poorly and utilized different coping strategies.
      CONCLUSIONS: The appraisals made about stressors differentiated the groups and
      was associated with differences in coping and distress levels. This suggests that
      treatment strategies focusing on stress management and enhancing coping skills
      might be important components of preventive interventions.

PMID- 21729340
TI  - Using a semi-structured interview to explore imagery experienced during social
      anxiety for clients with a diagnosis of psychosis: an exploratory study conducted
      within an early intervention for psychosis service.
AB  - BACKGROUND: Social phobia frequently occurs as a comorbid condition, with high
      rates reported among people with psychosis. Little is known about the nature of
      social anxiety in this population or whether current psychological theories
      apply. AIMS: This paper aims to develop and pilot a suitable measure to explore
      imagery experienced by participants with comorbid psychosis and social anxiety
      and to provide preliminary indications as to its nature. METHOD: A semi
      structured interview exploring imagery was used with seven participants (adapted
      from Hackmann, Surawy and Clark, 1998) and the results were analysed using
      qualitative template analysis. RESULTS: Initial indications from this sample
      suggest that some participants experience typical social anxiety images, as
      identified by Hackmann et al. (1998). However, some experience images that appear
      more threatening, and may be related to residual psychotic paranoia. Image
      perspective was also explored: typical social anxiety images tended to be seen
      from an observer perspective, while those that may have been more related to
      psychosis tended to be seen from a field perspective. CONCLUSIONS: This
      exploratory study has facilitated the careful adaptation and development of an
      imagery interview for use in this population and has suggested areas for further
      research and raised questions around clinical implications.

PMID- 21729341
TI  - The role of cognition in school refusal: an investigation of automatic thoughts
      and cognitive errors.
AB  - AIMS: The purpose of this study was to investigate the cognitions of anxious
      school refusers. The cognitive constructs under investigation included negative
      cognition commonly linked to youth anxiety (i.e. negative automatic thoughts and
      cognitive errors) and positive automatic thoughts. METHOD: The cognition of
      school refusers (n = 50) and youth from a community sample (n = 181) was assessed
      with the Children's Automatic Thoughts Scale-Negative/Positive and the Children's
      Negative Cognitive Error Questionnaire-Revised. RESULTS: When controlling for
      anxiety, school refusers were found to report more negative automatic thoughts
      concerning personal failure, fewer negative automatic thoughts concerning
      hostility, and fewer positive automatic thoughts. Negative automatic thoughts
      concerning personal failure and hostility, and the negative cognitive error of
      overgeneralizing were found to independently predict school refusal. CONCLUSIONS:
      The findings underscore the importance of further researching the role of
      cognition in the development, maintenance, and treatment of anxiety-based school
      refusal.

PMID- 21729342
TI  - Development and validation of a brief measure of therapeutically-induced change.
AB  - BACKGROUND: A premise of cognitive behavioural treatment is that individuals make
      cognitive, behavioural and situational changes prompted by interventions and that
      these changes bring about improvements in targeted outcomes. AIMS: The present
      project set out to provide reliability and validity information for a brief
      measure of therapeutically induced change. METHODS: A total of 281 participants,
      comprising three samples who took part in three different intervention studies,
      completed items relating to cognitive, behavioural and situational changes and
      completed measures relating to the intervention in which they participated.
      RESULTS: The internal consistency of the scale assessing therapeutically induced
      change was high in the three samples. The scale showed evidence of validity
      through association with (1) more involvement in an intervention (2) reporting
      that an intervention was meaningful (3) being instructed to incorporate insights
      gained from an intervention into one's daily life (4) greater decreases in
      psychological distress and negative affect from pre-intervention to post
      intervention, and (5) greater increases in positive affect from pre-intervention
      to post-intervention. CONCLUSIONS: The therapeutically-induced change scale may
      have utility as a process measure in various interventions.

PMID- 21729343
TI  - An evaluation of a CBT group for women with low self-esteem.
AB  - BACKGROUND: Self-esteem is an important factor in the development and maintenance
      of good psychological health. Low self-esteem can be a consequence of mental
      health disorders (such as depression, anxiety and panic) or it can be a
      vulnerability factor for the development of such problems. AIMS AND METHOD: The
      current study reports pilot findings from a Cognitive Behavioural Therapy (CBT)
      group intervention for 37 adult women with low self-esteem, based on Fennell's
      Overcoming Low Self-Esteem Self-Help Course. RESULTS: Findings suggest that the
      group is (statistically and clinically) effective at increasing levels of self
      esteem and at reducing levels of depression and anxiety. CONCLUSIONS: Together,
      results suggest that the group provides an efficient and therapeutically
      beneficial service. However, since these findings are limited by the lack of
      control or follow-up data, they warrant further investigation.

PMID- 21729344
TI  - Self-verification and social anxiety: preference for negative social feedback and
      low social self-esteem.
AB  - BACKGROUND: A self-verification model of social anxiety views negative social
      self-esteem as a core feature of social anxiety. This core feature is proposed to
      be maintained through self-verification processes, such as by leading individuals
      with negative social self-esteem to prefer negative social feedback. This model
      is tested in two studies. METHODS: In Study 1, questionnaires were administered
      to a college sample (N = 317). In Study 2, questionnaires were administered to
      anxiety disordered patients (N = 62) before and after treatment. RESULTS: Study 1
      developed measures of preference for negative social feedback and social self
      esteem, and provided evidence of their incremental validity in a college sample.
      Study 2 found that these two variables are not strongly related to fears of
      evaluation, are relatively unaffected by a treatment that targets such fears, and
      predict residual social anxiety following treatment. CONCLUSIONS: Overall, these
      studies provide preliminary evidence for a self-verification model of social
      anxiety.

PMID- 21729345
TI  - Parental overprotection and metacognitions as predictors of worry and anxiety.
AB  - BACKGROUND: Parental overprotection may have a direct effect on worry through
      hindering children's exploration experiences and preventing the learning of
      action-oriented coping strategies (Cheron, Ehrenreich and Pincus, 2009; Nolen
      Hoeksema, Wolfson, Mumme and Guskin, 1995) and an indirect effect through
      fostering the development of maladaptive metacognitions that are associated with
      the activation of worry and the escalation of anxiety (Wells, 2000). AIM: The aim
      was to investigate the relative contribution of recalled parental overprotection
      in childhood and metacognitions in predicting current levels of worry. METHOD: A
      community sample (n = 301) was administered four self-report instruments to
      assess parental overprotection, metacognitions, anxiety and worry. RESULTS:
      Metacognitions were found to predict levels of worry independently of gender,
      anxiety and parental overprotection. They were also found to predict anxiety
      independently of gender, worry and parental overprotection. CONCLUSIONS: The
      combination of a family environment perceived to be characterized by
      overprotection and high levels of maladaptive metacognitions are a risk factor
      for the development of worry.

PMID- 21729346
TI  - The Illusory Beliefs Inventory: a new measure of magical thinking and its
      relationship with obsessive compulsive disorder.
AB  - BACKGROUND: Magical thinking has been proposed to have an aetiological role in
      obsessive compulsive disorder (OCD). AIMS: To address the limitations of existing
      measures of magical thinking we developed and validated a new 24-item measure of
      magical thinking, the Illusory Beliefs Inventory (IBI). METHOD: The validation
      sample comprised a total of 1194 individuals across two samples recruited via an
      Internet based survey. RESULTS: Factor analysis identified three subscales
      representing domains relevant to the construct of magical thinking: Magical
      Beliefs, Spirituality, and Internal State and Thought Action Fusion. The scale
      had excellent internal consistency and evidence of convergent and discriminant
      validity. Evidence of criterion-related concurrent validity confirmed that
      magical thinking is a cognitive domain associated with OCD and is largely
      relevant to neutralizing, obsessing and hoarding symptoms. CONCLUSIONS: It is
      important for future studies to extend the evidence of the psychometric
      properties of the IBI in new populations and to conduct longitudinal studies to
      examine the aetiological role of magical thinking.

PMID- 21729347
TI  - Non-viral genetic transfection of rat Schwann cells with FuGENE HD(c) lipofection
      and AMAXA(c) nucleofection is feasible but impairs cell viability.
AB  - PURPOSE: To determine transfection efficiency of FuGENE HD(c) lipofection and
      AMAXA(c) nucleofection on rat Schwann cells (SC). METHODS: The ischiadic and
      median nerves of 6-8 week old Lewis rats were cultured in modified melanocyte
      growth medium. SCs were genetically transfected with green fluorescent protein
      (GFP) as reporter gene using FuGENE HD(c) lipofection and AMAXA(c) nucleofection.
      Transfection rates were determined by visualization of GFP fluorescence under
      fluorescence microscopy and cell counting. Transfected cell to non-transfected
      cell relation was determined. RESULTS: Purity of Schwann cell culture was 88% as
      determined by immunohistologic staining. Transfection rate of FuGENE HD(c)
      lipofection was 2%, transfection rate of AMAXA(c) nucleofection was 10%. With
      both methods, Schwann cells showed pronounced aggregation behavior which made
      them unfeasible for further cultivation. Settling of Schwann cells on laminin and
      poly-L-ornithine coated plates was compromised by either method. CONCLUSION: Non
      viral transfection of rat SC with FuGENE HD(c) lipofection and AMAXA(c)
      nucleofection is basically possible with a higher transfection rate for
      nucleofection than for lipofection. As cell viability is compromised by either
      method however, viral transfection is to be considered if higher efficiency is
      required.

PMID- 21729348
TI  - Continuum simulations of biomembrane dynamics and the importance of hydrodynamic
      effects.
AB  - Traditional particle-based simulation strategies are impractical for the study of
      lipid bilayers and biological membranes over the longest length and time scales
      (microns, seconds and longer) relevant to cellular biology. Continuum-based
      models developed within the frameworks of elasticity theory, fluid dynamics and
      statistical mechanics provide a framework for studying membrane biophysics over a
      range of mesoscopic to macroscopic length and time regimes, but the application
      of such ideas to simulation studies has occurred only relatively recently. We
      review some of our efforts in this direction with emphasis on the dynamics in
      model membrane systems. Several examples are presented that highlight the
      prominent role of hydrodynamics in membrane dynamics and we argue that careful
      consideration of fluid dynamics is key to understanding membrane biophysics at
      the cellular scale.

PMID- 21729351
TI  - Do molecules matter more than morphology? Promises and pitfalls in parasites.
AB  - Systematics involves resolving both the taxonomy and phylogenetic placement of
      organisms. We review the advantages and disadvantages of the two kinds of
      information commonly used for such inferences--morphological and molecular data-
      as applied to the systematics of metazoan parasites generally, with special
      attention to the malaria parasites. The problems that potentially confound the
      use of morphology in parasites include challenges to consistent specimen
      preservation, plasticity of features depending on hosts or other environmental
      factors, and morphological convergence. Molecular characters such as DNA
      sequences present an alternative data source and are particularly useful when not
      all the parasite's life stages are present or when parasitaemia is low.
      Nonetheless, molecular data can bring challenges that include troublesome DNA
      isolation, paralogous gene copies, difficulty in developing molecular markers,
      and preferential amplification in mixed species infections. Given the
      differential benefits and shortcomings of both molecular and morphological
      characters, both should be implemented in parasite taxonomy and phylogenetics.

PMID- 21729350
TI  - A new way to see RNA.
AB  - Unlike proteins, the RNA backbone has numerous degrees of freedom (eight, if one
      counts the sugar pucker), making RNA modeling, structure building and prediction
      a multidimensional problem of exceptionally high complexity. And yet RNA tertiary
      structures are not infinite in their structural morphology; rather, they are
      built from a limited set of discrete units. In order to reduce the dimensionality
      of the RNA backbone in a physically reasonable way, a shorthand notation was
      created that reduced the RNA backbone torsion angles to two (eta and theta,
      analogous to phi and psi in proteins). When these torsion angles are calculated
      for nucleotides in a crystallographic database and plotted against one another,
      one obtains a plot analogous to a Ramachandran plot (the eta/theta plot), with
      highly populated and unpopulated regions. Nucleotides that occupy proximal
      positions on the plot have identical structures and are found in the same units
      of tertiary structure. In this review, we describe the statistical validation of
      the eta/theta formalism and the exploration of features within the eta/theta
      plot. We also describe the application of the eta/theta formalism in RNA motif
      discovery, structural comparison, RNA structure building and tertiary structure
      prediction. More than a tool, however, the eta/theta formalism has provided new
      insights into RNA structure itself, revealing its fundamental components and the
      factors underlying RNA architectural form.

PMID- 21729352
TI  - Synergy advances parasite taxonomy and systematics: an example from elasmobranch
      tapeworms.
AB  - The synergism facilitated by a series of recent developments has conspired to
      catalyze rapid advancements in the taxonomy and systematics of elasmobranch
      tapeworms. These developments are: (1) increased interest in global biodiversity;
      (2) globalization-facilitated communication; (3) enhanced microscopic and digital
      technologies; (4) availability of web-based taxonomic resources; (5) ease of use
      and low cost of molecular techniques and (6) the impressive repertoire of
      available phylogenetic methods. As a consequence, an estimation of global
      elasmobranch tapeworm diversity is now within our grasp, as is a basic
      understanding of the effort and resources required to complete the discovery and
      description of this fauna globally. The generation of robust hypotheses of the
      phylogenetic relationships for most elasmobranch-parasitizing cestode orders is
      also well underway. An international community of cestodologists has emerged and
      through their sharing of knowledge and specimens is making great strides towards
      expanding knowledge of the cestode fauna of vertebrates worldwide. It is
      important that these efforts continue to move forward in a collaborative fashion,
      integrating morphological and molecular data, but also fully engaging
      elasmobranch taxonomists and systematists. It is equally important that efforts
      to characterize and describe global biodiversity are not derailed by such
      seductive, but ultimately unrewarding impracticable initiatives as molecular
      taxonomy. Integrated taxonomy is certainly not for the feint of heart, but those
      with the courage to pursue this strategy will be responsible for maintaining and
      enhancing the biologically relevant context required for effective species
      recognition well into the future.

PMID- 21729349
TI  - Expanding the proteome: disordered and alternatively folded proteins.
AB  - Proteins provide much of the scaffolding for life, as well as undertaking a
      variety of essential catalytic reactions. These characteristic functions have led
      us to presuppose that proteins are in general functional only when well
      structured and correctly folded. As we begin to explore the repertoire of
      possible protein sequences inherent in the human and other genomes, two stark
      facts that belie this supposition become clear: firstly, the number of apparent
      open reading frames in the human genome is significantly smaller than appears to
      be necessary to code for all of the diverse proteins in higher organisms, and
      secondly that a significant proportion of the protein sequences that would be
      coded by the genome would not be expected to form stable three-dimensional (3D)
      structures. Clearly the genome must include coding for a multitude of alternative
      forms of proteins, some of which may be partly or fully disordered or
      incompletely structured in their functional states. At the same time as this
      likelihood was recognized, experimental studies also began to uncover examples of
      important protein molecules and domains that were incompletely structured or
      completely disordered in solution, yet remained perfectly functional. In the
      ensuing years, we have seen an explosion of experimental and genome-annotation
      studies that have mapped the extent of the intrinsic disorder phenomenon and
      explored the possible biological rationales for its widespread occurrence.
      Answers to the question 'why would a particular domain need to be unstructured?'
      are as varied as the systems where such domains are found. This review provides a
      survey of recent new directions in this field, and includes an evaluation of the
      role not only of intrinsically disordered proteins but also of partially
      structured and highly dynamic members of the disorder-order continuum.

PMID- 21729353
TI  - Species-specific treatment effects of helminth/HIV-1 co-infection: a systematic
      review and meta-analysis.
AB  - In sub-Saharan Africa, over 22 million people are estimated to be co-infected
      with both helminths and HIV-1. Several studies have suggested that de-worming
      individuals with HIV-1 may delay HIV-1 disease progression, and that the benefit
      of de-worming may vary by individual helminth species. We conducted a systematic
      review and meta-analysis of the published literature to determine the effect of
      treatment of individual helminth infections on markers of HIV-1 progression (CD4
      count and HIV viral load). There was a trend towards an association between
      treatment for Schistosoma mansoni and a decrease in HIV viral load (Weighted mean
      difference (WMD)=-0.10; 95% Confidence interval (CI): -0.24, 0.03), although this
      association was not seen for Ascaris lumbricoides, hookworm or Trichuris
      trichiura. Treatment of A. lumbricoides, S. mansoni, hookworm or T. trichiura was
      not associated with a change in CD4 count. While pooled data from randomized
      trials suggested clinical benefit of de-worming for individual helminth species,
      these effects decreased when observational data were included in the pooled
      analysis. While further trials are needed to confirm the role of anthelmintic
      treatment in HIV-1 co-infected individuals, providing anthelmintics to
      individuals with HIV-1 may be a safe, inexpensive and practical intervention to
      slow progression of HIV-1.

PMID- 21729354
TI  - Bacterial symbiont and salivary peptide evolution in the context of leech
      phylogeny.
AB  - The evolutionary history of leeches is employed as a general framework for
      understanding more than merely the systematics of this charismatic group of
      annelid worms, and serves as a basis for understanding blood-feeding related
      correlates ranging from the specifics of gut-associated bacterial symbionts to
      salivary anticoagulant peptides. A variety of medicinal leech families were
      examined for intraluminal crop bacterial symbionts. Species of Aeromonas and
      Bacteroidetes were characterized with DNA gyrase B and 16S rDNA. Bacteroidetes
      isolates were found to be much more phylogenetically diverse and suggested
      stronger evidence of phylogenetic correlation than the gammaproteobacteria.
      Patterns that look like co-speciation with limited taxon sampling do not in the
      full context of phylogeny. Bioactive compounds that are expressed as gene
      products, like those in leech salivary glands, have 'passed the test' of
      evolutionary selection. We produced and bioinformatically mined salivary gland
      EST libraries across medicinal leech lineages to experimentally and statistically
      evaluate whether evolutionary selection on peptides can identify structure
      function activities of known therapeutically relevant bioactive compounds like
      antithrombin, hirudin and antistasin. The combined information content of a well
      corroborated leech phylogeny and broad taxonomic coverage of expressed proteins
      leads to a rich understanding of evolution and function in leech history.

PMID- 21729356
TI  - The hair follicle bulge: a niche for adult stem cells.
AB  - Adult stem cells (SCs) are essential for tissue homeostasis and wound repair.
      They have the ability to both self-renew and differentiate into multiple cell
      types. They often reside in specialized microenvironments or niches that preserve
      their proliferative and tissue regenerative capacity. The murine hair follicle
      (HF) has a specialized and permanent compartment--the bulge, which safely lodges
      SCs and provides the necessary molecular cues to regulate their function. The HF
      undergoes cyclic periods of destruction, regeneration, and rest, making it an
      excellent system to study SC biology.

PMID- 21729355
TI  - Screening trematodes for novel intervention targets: a proteomic and
      immunological comparison of Schistosoma haematobium, Schistosoma bovis and
      Echinostoma caproni.
AB  - With the current paucity of vaccine targets for parasitic diseases, particularly
      those in childhood, the aim of this study was to compare protein expression and
      immune cross-reactivity between the trematodes Schistosoma haematobium, S. bovis
      and Echinostoma caproni in the hope of identifying novel intervention targets.
      Native adult parasite proteins were separated by 2-dimensional gel
      electrophoresis and identified through electrospray ionisation tandem mass
      spectrometry to produce a reference gel. Proteins from differential gel
      electrophoresis analyses of the three parasite proteomes were compared and
      screened against sera from hamsters infected with S. haematobium and E. caproni
      following 2-dimensional Western blotting. Differential protein expression between
      the three species was observed with circa 5% of proteins from S. haematobium
      showing expression up-regulation compared to the other two species. There was 91%
      similarity between the proteomes of the two Schistosoma species and 81% and 78.6%
      similarity between S. haematobium and S. bovis versus E. caproni, respectively.
      Although there were some common cross-species antigens, species-species targets
      were revealed which, despite evolutionary homology, could be due to phenotypic
      plasticity arising from different host-parasite relationships. Nevertheless, this
      approach helps to identify novel intervention targets which could be used as
      broad-spectrum candidates for future use in human and veterinary vaccines.

PMID- 21729357
TI  - Deep tissue fluorescent imaging in scattering specimens using confocal
      microscopy.
AB  - In scattering specimens, multiphoton excitation and nondescanned detection
      improve imaging depth by a factor of 2 or more over confocal microscopy; however,
      imaging depth is still limited by scattering. We applied the concept of clearing
      to deep tissue imaging of highly scattering specimens. Clearing is a remarkably
      effective approach to improving image quality at depth using either confocal or
      multiphoton microscopy. Tissue clearing appears to eliminate the need for
      multiphoton excitation for deep tissue imaging.

PMID- 21729358
TI  - Structure and chemistry across interfaces at nanoscale of a Ge quantum well
      embedded within rare earth oxide layers.
AB  - Structure and chemistry across the rare earth oxide-Ge interfaces of a Gd2O3-Ge
      Gd2O3 heterostructure grown on p-Si (111) substrate using encapsulated solid
      phase epitaxy method have been studied at nanoscale using various transmission
      electron microscopy methods. The structure across both the interfaces was
      investigated using reconstructed phase and amplitude at exit plane. Chemistry
      across the interfaces was explored using elemental mapping, high-angle annular
      dark-field imaging, electron energy loss spectroscopy, and energy dispersive X
      ray spectrometry. Results demonstrate the structural and chemical abruptness of
      both the interfaces, which is most essential to maintain the desired quantum
      barrier structure.

PMID- 21729359
TI  - Inbreeding and population subdivision in Cordoba province, Argentina, at the end
      of the eighteenth century.
AB  - Marital isonymy is frequently used to estimate inbreeding and the repeated pairs
      method is useful to investigate whether the population under examination has
      subdivisions. These methods can also be applied to registers, such as population
      censuses, where both spouses' surnames are noted. In this paper, the 1795 census
      for Cordoba province is analysed. Numerically speaking, Spanish and mixed-race
      people are the major ethno-social groups in the register. In order to estimate
      inbreeding, the isonymic method was applied to both groups, at provincial and at
      parish level. To appreciate to what extent the parishes were genetically
      isolated, Wright's Fst was also calculated. The repeated pairs method was also
      used for both groups to assess if population subdivision existed in the units
      under study. Finally, to evaluate whether the subdivision based on surnames
      reflected the ethno-social stratification, the same method was used considering
      the two groups together. At the provincial scale, both groups displayed low
      inbreeding and micro-differentiation, although the former was higher for the
      Spanish and the latter for mixed-race groups, which could indicate a more marked
      conjugal selectivity in the Spanish. At the parish scale, preferences for
      isonymic spouses were not pronounced either in Spanish or in mixed-race groups;
      in the Spanish group population subdivision prevailed, with the opposite
      occurring in the mixed-race group. The estimations from repeated pairs, taking
      the two groups together, indicated that for the studied populations the surnames
      do not allow the two groups to be differentiated into isolated reproductive
      units.

PMID- 21729360
TI  - Motivations for entry into sex work and HIV risk among mobile female sex workers
      in India.
AB  - This paper assesses the reasons for entry into sex work and its association with
      HIV risk behaviours among mobile female sex workers (FSWs) in India. Data were
      collected from a cross-sectional survey conducted in 22 districts across four
      high HIV prevalence states in India during 2007-2008. Analyses were limited to
      5498 eligible mobile FSWs. The reasons given by FSWs for entering sex work and
      associations with socio-demographic characteristics were assessed. Reported
      reasons for entering sex work include poor or deprived economic conditions;
      negative social circumstances in life; own choice; force by an external person;
      and family tradition. The results from multivariate analyses indicate that those
      FSWs who entered sex work due to poor economic conditions or negative social
      circumstances in life or force demonstrated elevated levels of current
      inconsistent condom use as well as in the past in comparison with those FSWs who
      reported entering sex work by choice or family tradition. This finding indicates
      the need for a careful assessment of the pre-entry contexts among HIV prevention
      interventions since these factors may continue to hinder the effectiveness of
      efforts to reduce the spread of HIV/AIDS in India and elsewhere.

PMID- 21729361
TI  - Health care utilization, socioeconomic factors and child health in India.
AB  - This paper models the proximate determinants of height, weight and haemoglobin
      concentration of over 25,000 Indian children using data from the National Family
      Health Survey-3. The effects of public and private health care service
      utilization, food consumption patterns and maternal health status on child health
      were investigated in a multidisciplinary framework. Methodological issues such as
      potential endogeneity of explanatory variables and the appropriateness of
      combining height and weight as the body mass index were tackled. The results from
      models for children's heights and weight showed beneficial effects of child
      vaccinations against DPT, polio and measles, and negative effects of not
      utilizing government health facilities. The models for children's haemoglobin
      concentration indicated beneficial effects of food consumption patterns and
      treatment against intestinal parasites. The results provide several insights for
      improving child health in India.

PMID- 21729362
TI  - Consanguineous marriages in Afghanistan.
AB  - The present cross-sectional study was done in order to illustrate the prevalence
      and types of consanguineous marriages among Afghanistan populations. Data on
      types of marriages were collected using a simple questionnaire. The total number
      of couples in the study was 7140 from the following provinces: Badakhshan,
      Baghlan, Balkh, Bamyan, Kabul, Kunduz, Samangan and Takhar. Consanguineous
      marriages were classified by the degree of relationship between couples: double
      first cousins, first cousins, first cousins once removed, second cousins and
      beyond second cousins. The coefficient of inbreeding (F) was calculated for each
      couple and the mean coefficient of inbreeding (alpha) estimated for each
      population. The proportion of consanguineous marriages in the country was 46.2%,
      ranging from 38.2% in Kabul province to 51.2% in Bamyan province. The equivalent
      mean inbreeding coefficient (alpha) was 0.0277, and ranged from 0.0221 to 0.0293
      in these two regions. There were significant differences between provinces for
      frequencies of different types of marriages (p<0.001). First cousin marriages
      (27.8%) were the most common type of consanguineous marriages, followed by double
      first cousin (6.9%), second cousin (5.8%), beyond second cousin (3.9%) and first
      cousin once removed (1.8%). There were significant differences between ethnic
      groups for the types of marriages (chi2=177.6, df=25, p<0.001). Tajiks (Soni) and
      Turkmens (also Pashtuns) showed the lowest (alpha=0.0250) and highest
      (alpha=0.0297) mean inbreeding coefficients, respectively, among the ethnic
      groups in Afghanistan. The study shows that Afghanistan's populations, like other
      Islamic populations, have a high level of consanguinity.

PMID- 21729363
TI  - Socioeconomic status, marital status and childlessness in men and women: an
      analysis of census data from six countries.
AB  - This study compares the effects of two distinct forms of human capital - income
      and education - on marital status and childlessness separately by sex in six
      different countries. Nearly 10 million individual records on individuals aged 16
      to 50 were used from censuses from Brazil, Mexico, Panama, South Africa, USA and
      Venezuela dating from 2000 or later, to analyse the relationship between
      education, income and marital status and childlessness in men and women.
      Regarding income, the findings for both outcome variables are strongly consistent
      across all six countries. Highest-income males and lower-income females have the
      highest proportion of ever-married and the lowest proportion of childlessness
      (using a proxy for childlessness: own children in the household or not). There is
      no corresponding consistency of findings as regards education either between the
      sexes or among the countries. To conclude, a lower percentage of low-income men
      are selected by females, because for women male status and resources provided by
      men are important criteria in mate selection. Therefore a higher proportion of
      low-income men remain unmarried and childless. Thus selection seems to play a
      role in modern societies.

PMID- 21729364
TI  - Anthropometric, body composition and health determinants of active ageing: a
      gender approach.
AB  - This study applied a gender perspective to establish some of the anthropometric,
      body composition, health and socio-cultural determinants of active ageing. The
      variable 'active ageing' (presence/absence) was created based on cognitive and
      disability/illness/physical functioning, subjective health, satisfaction with
      life and productive activity performed, and used in predictive models to
      establish its relationship with anthropometric variables, physical health
      indicators and educational level. The sample consisted of 456 home-living
      individuals (169 men and 287 women; age range 54-75 years) from Madrid and Toledo
      in Spain. The women had a higher prevalence of obesity than the men (37.6% vs
      29.0%), significantly greater fat accumulation in the abdominal area and worst
      perceived health (p=0.003). The frequency of active agers is higher in men than
      in women (38.4% vs 21.9%; p<0.001). Men and women were found to have distinctive
      ageing patterns. Health factors condition the presence of active ageing in women,
      while education factors are also relevant in men.

PMID- 21729365
TI  - The impact of scaffolding and overhearing on young children's use of the spatial
      terms between and middle.
AB  - The primary goal was to specify the impact of scaffolding and overhearing on
      young children's use of the spatial terms between and middle. Four- and five-year
      old children described the location of a mouse hidden between two furniture items
      in a dollhouse with assistance from a parent. Children's use of between and
      middle increased significantly across trials, and in concert, parents' directive
      scaffolding involving middle decreased across trials. In the second study, three
      common scaffolding types (Between Directive, Middle Directive, non-directive)
      were compared with a no prompt condition by having children receive prompts from
      a doll and with overhearing conditions in which children overheard conversations
      between two adult experimenters containing between or middle. Children's use of
      between and middle was much more frequent following directive prompting than
      following non-directive prompting, no prompting, or overhearing. Moreover,
      children showed some evidence of using between and middle in response to non
      directive prompting and overhearing.

PMID- 21729366
TI  - Beyond syntactic priming: evidence for activation of alternative syntactic
      structures.
AB  - Priming methodology was previously used to investigate children's ability to
      represent abstract syntactic forms. Existing evidence indicates that following
      exposure to a particular syntactic structure (such as the passive voice), English
      speaking children increase their production of that structure with new lexical
      items. In the present work, we utilize priming methodology to explore whether
      exposure to passive primes may increase children's production of sentences that
      have a different structure but share a similar purpose in discourse. We report
      three studies, two involving English- and Russian-speaking children, and a third
      involving Russian-speaking adults. Unlike English, Russian offers a variety of
      syntactic forms that emphasize the patient of a transitive action, thus
      fulfilling the discourse function of the passive. We found that English speakers
      increased the use of the particular syntactic form presented in the prime,
      whereas Russian speakers increased their production of several different
      syntactic forms used to emphasize the patient of the action.

PMID- 21729367
TI  - Young children fail to fully generalize a novel argument structure construction
      when exposed to the same input as older learners.
AB  - The present study exposed five-year-olds (M=5 ; 2), seven-year-olds (M=7 ; 6) and
      adults (M=22 ; 4) to instances of a novel phrasal construction, then used a
      forced choice comprehension task to evaluate their learning of the construction.
      The abstractness of participants' acquired representations of the novel
      construction was evaluated by varying the degree of lexical overlap that test
      items had with exposure items. We found that both child groups were less
      proficient than adults, but seven-year-olds showed evidence of across-the-board
      generalization whereas five-year-olds were sensitive to lexical overlap at test.
      This outcome is consistent with more conservative, item-based learning of
      syntactic patterns in younger children. Additionally, unlike adults and seven
      year-olds, five-year-olds showed no evidence of having mastered the novel
      construction's linking rules. Thus, younger learners are less likely to
      generalize abstract argument structure constructions when exposed to the same
      systematic input as older learners.

PMID- 21729368
TI  - Is prosodic development correlated with grammatical and lexical development?
      Evidence from emerging intonation in Catalan and Spanish.
AB  - This investigation focuses on the development of intonation patterns in four
      Catalan-speaking children and two Spanish-speaking children between 0 ; 11 and 2
      ; 4. Pitch contours were prosodically analyzed within the Autosegmental Metrical
      framework in all meaningful utterances, for a total of 6558 utterances. The
      pragmatic meaning and communicative function were also assessed. Three main
      conclusions arise from the results. First, the study shows that the Autosegmental
      Metrical model can be successfully used to transcribe early intonation contours.
      Second, results reveal that children's emerging intonation is largely independent
      of grammatical development, and generally it develops well before the appearance
      of two-word combinations. As for the relationship between lexical and
      intonational development, the data show that the emergence of intonational
      grammar is related to the onset of speech and the presence of a small lexicon.
      Finally, we discuss the implications of these results for the biological
      hypothesis of intonational production.

PMID- 21729369
TI  - Extended Statistical Learning as an account for slow vocabulary growth.
AB  - Stokes (2010) compared the lexicons of English-speaking late talkers (LT) with
      those of their typically developing (TD) peers on neighborhood density (ND) and
      word frequency (WF) characteristics and suggested that LTs employed learning
      strategies that differed from those of their TD peers. This research sought to
      explore the cross-linguistic validity of this conclusion. The lexicons
      (production, not recognition) of 208 French-speaking two-year-old children were
      coded for ND and WF. Regression revealed that ND and WF together predicted 62% of
      the variance in vocabulary size, with ND and WF uniquely accounting for 53% and
      9% of that variance respectively. Epiphenomenal findings were ruled out by
      comparison of simulated data sets with the actual data. A generalized Mann
      Whitney test showed that children with small vocabularies had significantly
      higher ND values and significantly lower WF values than children with large
      vocabularies. An EXTENDED STATISTICAL LEARNING theory is proposed to account for
      the findings.

PMID- 21729370
TI  - Speaker reliability in preschoolers' inferences about the meanings of novel
      words.
AB  - Preschoolers participated in a modified version of the disambiguation task,
      designed to test whether the pragmatic environment generated by a reliable or
      unreliable speaker affected how children interpreted novel labels. Two objects
      were visible to children, while a third was only visible to the speaker (a fact
      known by the child). Manipulating whether a novel object was visible to both
      interlocutors or hidden from the child tested the child's understanding of
      pragmatic expectations of interlocutor competence. When interacting with a
      speaker with a history of accurately labeling familiar objects, children
      responded appropriately in both cases. When interacting with a speaker who
      previously generated inaccurate labels for familiar objects, children's behavior
      and eye-movements reflected their belief that the speaker was not a competent
      communicator. These data support the hypothesis that children consider the
      pragmatic environment constructed by an interlocutor when that speaker asks them
      to make a lexical inference.

PMID- 21729371
TI  - Vocabulary development in Greek children: a cross-linguistic comparison using the
      Language Development Survey.
AB  - This study investigated vocabulary size and vocabulary composition in Greek
      children aged 1;6 to 2;11 using a Greek adaptation of Rescorla's Language
      Development Survey (LDS; Rescorla, 1989). Participants were 273 toddlers coming
      from monolingual Greek-speaking families. Greek LDS data were compared with US
      LDS data obtained from the instrument's normative sample (Achenbach & Rescorla,
      2000). Vocabulary size increased markedly with age, but Greek toddlers appeared
      to get off to a slower start in early word learning than US children. The
      correlation between percentage word use scores in Greek and US samples was
      moderate in size, indicating considerable overlap but some differences. Common
      nouns were the largest category among the fifty most frequent words in both
      samples. Numbers of adjectives and verbs were comparable across languages, but
      people and closed-class words were more numerous in the Greek sample. Finally,
      Greek late talkers showed similar patterns of vocabulary composition to those
      observed in typically developing Greek children.

PMID- 21729372
TI  - The effect of energy-protein supplementation on weight, body composition and
      handgrip strength among pulmonary tuberculosis HIV-co-infected patients:
      randomised controlled trial in Mwanza, Tanzania.
AB  - Undernutrition is common among smear-positive pulmonary tuberculosis (PTB+)
      patients. Micronutrient supplementation may improve treatment outcomes, but it is
      unclear whether additional energy-protein would be beneficial. The present study
      aimed to assess the effect of energy-protein supplementation on weight, body
      composition and handgrip strength against a background of high micronutrient
      intake during tuberculosis (TB) treatment. A total of 377 PTB+ patients co
      infected with HIV were randomly allocated one or six biscuits daily for 60 d
      during TB treatment. Weight, arm fat area, arm muscle area and handgrip strength
      were assessed at baseline and 2 and 5 months. There were no effects on any
      outcome at 2 months, but energy-protein supplementation was associated with a 1.3
      (95 % CI - 0.1, 2.8) kg marginally significant gain in handgrip strength at 5
      months. However, after 2 months, energy-protein supplementation led to a weight
      gain of 1.9 (95 % CI 0.1, 3.7) kg among patients with cluster of differentiation
      4 (CD4) counts >= 350 cells/MUl, but not among patients with low CD4 counts ( -
      0.2 kg; 95 % CI - 1.3, 0.8, Pinteraction = 0.03). Similarly, at 5 months, energy
      protein supplementation led to a 2.3 (95 % CI 0.6, 4.1) kg higher handgrip
      strength gain among patients with CD4 counts < 350 cells/MUl, but not in those
      with high CD4 counts (Pinteraction = 0.04). In conclusion, energy-protein
      supplementation to PTB+ HIV-co-infected patients had no overall effects on weight
      and body composition, but was associated with marginally significant gain in
      handgrip strength. More research is needed to develop an effective supplement,
      before it is recommended to TB programmes.

PMID- 21729373
TI  - Fine metabolic regulation in ruminants via nutrient-gene interactions: saturated
      long-chain fatty acids increase expression of genes involved in lipid metabolism
      and immune response partly through PPAR-alpha activation.
AB  - Madin-Darby Bovine Kidney cells cultured with 150 MUm of Wy-14 643 (WY, PPARalpha
      agonist) or twelve long-chain fatty acids (LCFA; 16 : 0, 18 : 0, cis-9-18 : 1,
      trans-10-18 : 1, trans-11-18 : 1, 18 : 2n-6, 18 : 3n-3, cis-9, trans-11-18 : 2,
      trans-10, cis-12-18 : 2, 20 : 0, 20 : 5n-3 and 22 : 6n-3) were used to uncover
      PPAR-alpha target genes and determine the effects of LCFA on expression of thirty
      genes with key functions in lipid metabolism and inflammation. Among fifteen
      known PPAR-alpha targets in non-ruminants, ten had greater expression with WY,
      suggesting that they are bovine PPAR-alpha targets. The expression of SPP1 and
      LPIN3 was increased by WY, with no evidence of a similar effect in the published
      literature, suggesting that both represent bovine-specific PPAR-alpha targets. We
      observed the strongest effect on the expression of PPAR-alpha targets with 16 :
      0, 18 : 0 and 20 : 5n-3.When considering the overall effect on expression of the
      thirty selected genes 20 : 5n-3, 16 : 0 and 18 : 0 had the greatest effect
      followed by 20 : 0 and c9t11-18 : 2. Gene network analysis indicated an overall
      increase in lipid metabolism by WY and all LCFA with a central role of PPAR-alpha
      but also additional putative transcription factors. A greater increase in the
      expression of inflammatory genes was observed with 16 : 0 and 18 : 0. Among LCFA,
      20 : 5n-3, 16 : 0 and 18 : 0 were the most potent PPAR-alpha agonists. They also
      affected the expression of non-PPAR-alpha targets, eliciting an overall increase
      in the expression of genes related to lipid metabolism, signalling and
      inflammatory response. Data appear to highlight a teleological evolutionary
      adaptation of PPAR in ruminants to cope with the greater availability of
      saturated rather than unsaturated LCFA.

PMID- 21729374
TI  - Effect of melatonin treatment on the developmental potential of parthenogenetic
      and somatic cell nuclear-transferred porcine oocytes in vitro.
AB  - Melatonin secreted from the mammalian pineal gland is a free-radical scavenger
      that protects tissues from cell damage. The present study examined the effects of
      addition of melatonin to the culture medium on the developmental potential of
      parthenogenetic and somatic cell nuclear-transferred (SCNT) porcine oocytes.
      Supplementation of the maturation medium with melatonin did not increase the
      maturation rate, the proportion of oocytes that cleaved and developed into
      blastocysts after parthenogenetic activation, or the blastocyst cell number
      compared to controls. When 10-7 M melatonin was added to the culture medium, the
      proportion of parthenogenetic oocytes that developed to the 2-cell and 4-cell
      stages was significantly higher than that of controls. The potential of melatonin
      treated oocytes to develop into blastocysts was high but not significantly
      different from that of controls. The addition of 10-7 M melatonin to the culture
      medium did not increase the preimplantation development of SCNT oocytes.
      Melatonin treatment significantly reduced the levels of reactive oxygen species
      in 4-cell parthenogenetic and SCNT embryos, but did not reduce the proportion of
      apoptotic cells in parthenogenetic and SCNT blastocysts. Although the results
      indicated that parthenogenetic and SCNT melatonin -treated embryos had
      significantly lower levels of reactive oxygen species than controls, the
      potential of melatonin-treated embryos to develop into blastocysts was not
      significantly higher than that of controls, in contrast to previous reports. The
      beneficial effects of melatonin on the developmental potential of oocytes might
      depend on the culture conditions.

PMID- 21729375
TI  - Analysis of DNA looped domains organization during Triturus cristatus
      spermatogenesis.
AB  - Chromatin from eukaryotes is organized in DNA loops with sequential attachments
      to a nucleoskeleton named nuclear matrix. This organization plays major roles in
      replication, transcription, recombination, DNA repair, chromosome condensation
      and segregation. During spermatogenesis, chromatin undergoes several dynamic
      transitions, which are often associated with important changes not only in its
      physical conformation but even in its compositions and structure. To understand
      the periodical change in the functional organization of chromatin during
      spermatogenesis, the higher order organization of chromatin in different
      testicular cell types (pachytene spermatocytes, round spermatids) and the
      epididymal sperm of Triturus cristatus have been investigated. The expansion and
      the contraction of nucleoid DNA were measured with a fluorescence microscope
      following exposure of nucleoids to increasing concentrations of ethidium bromide
      (EtBr) (2.5-200 MUg/ml) as an intercalating dye to induce DNA-positive
      supercoils. Nucleoids from all studied cell types exhibited a biphasic change
      (condensed-relaxed-condensed) in size as a consequence of exposure to increasing
      concentrations of EtBr, indicating that they contained negatively supercoiled
      DNA. At higher EtBr concentrations, maximum positive supercoiling occurred in
      pachytene DNA loops. Our data suggest that pachytene DNA is the most open
      chromatin conformation in terms of EtBr intercalation.

PMID- 21729376
TI  - The effects of cysteine addition during in vitro maturation on the developmental
      competence, ROS, GSH and apoptosis level of bovine oocytes exposed to heat
      stress.
AB  - In the present study, we investigated the effects of various concentrations of
      cysteine (0.0, 0.6, 1.2 and 1.8 mM) added to the maturation medium on nuclear
      maturation and subsequent embryonic development of bovine oocytes exposed to heat
      stress (HS: set at 39.5  degrees C for 5 h, 40.0  degrees C for 5 h, 40.5 
      degrees C for 6 h, and 40.0  degrees C for 4 h versus 38.5  degrees C for 20 h as
      the control group). This regime mimicked the circadian rhythm of the vaginal
      temperature of lactating dairy cows during the summer season in southwestern
      Japan. Moreover, we also evaluated the oocyte's reactive oxygen species (ROS) and
      glutathione (GSH) levels and the apoptosis levels of the oocytes and cumulus
      cells in the presence or absence of 1.2 mM cysteine. As a result, HS in the
      without-cysteine group significantly suppressed (p < 0.05) both the nuclear
      maturation rate up to the metaphase (M)II stage and the blastocyst formation rate
      compared with that of the control group. In addition, this group showed
      significantly higher (p < 0.05) ROS levels and significantly lower (p < 0.05) GSH
      levels than those of the control group. Moreover, the level of TdT-mediated dUTP
      nick end labelling (TUNEL)-positive cumulus cells in the HS without-cysteine
      group was significantly higher (p < 0.05) than that of the control group.
      However, the addition of 1.2 mM cysteine to the maturation medium restored not
      only the nuclear maturation, blastocyst formation rates and GSH contents, but
      also increased the ROS and TUNEL-positive levels of the cumulus cells, but not
      oocytes, to that of the control group. These results indicate that the addition
      of 1.2 mM cysteine during in vitro maturation (IVM) may alleviate the influence
      of heat stress for oocyte developmental competence by increasing GSH content and
      inhibiting the production of oocyte ROS followed by apoptosis of cumulus cells.

PMID- 21729377
TI  - Isolation and culture of embryonic stem-like cells from pig nuclear transfer
      blastocysts of different days.
AB  - This study was conducted to establish pig embryonic stem (ES)-like cell lines
      from nuclear transfer blastocysts. A green fluorescent protein (GFP)-expressing
      cell line was used as the source of donor cells injected into the enucleated
      oocytes. Blastocysts were collected at D5 (the fifth day), D7 (the seventh day)
      and D9 (the ninth day). Differential staining was used to assay the viability and
      development of blastocysts from the 3 days. The number of inner cell mass (ICM)
      cells increased from 1.83 +/- 0.8 (D5) to 5.37 +/- 1.2 (D7) to 7.56 +/- 1.5 (D9).
      The expression profiles of embryonic stem (ES) cell factors (OCT4, SOX2, KLF4 and
      c-MYC) correlated best with the undifferentiated ES state and were identified by
      qPCR. The expression of the four factors was increased from D5 to D7, whereas the
      expression decreased from D7 to D9. We tried to isolate ES-like cells from these
      embryos. However, ES-like cells from the D7 blastocysts grew slowly and expressed
      alkaline phosphatase. The cells from the D9 blastocysts grew rapidly but did not
      express alkaline phosphatase. ES-like cells were not isolated from the D5
      blastocysts. These results show that the cells from the D7 embryos are
      pluripotent but grow slowly. The cells from the D9 embryos grow rapidly but start
      to lose pluripotency.

PMID- 21729378
TI  - Prediction of maturational competence of feline oocytes using supravital staining
      of cumulus cells by propidium iodide.
AB  - We examined the relationship between integrity of cumulus cells and nuclear
      maturation rate after in vitro culture to determine a non-invasive prediction of
      the maturational competence of feline oocytes. Feline cumulus-oocyte complexes
      (COCs) were collected from either small (400-800 MUm) or large (>=800 MUm)
      follicles. Immediately after collection, cumulus cells were evaluated
      morphologically (thickness of cumulus cell layers) and stained with propidium
      iodide (PI), which penetrates only non-viable cells. Cumulus cells without PI
      staining were judged as having good membrane integrity. After evaluation, COCs
      were cultured for 30 h and their nuclear maturation rate was determined. The
      nuclear maturation rate of oocytes derived from large follicles (89.8%) was
      higher (p < 0.05) than that from small follicles (60.8%). There was no difference
      in the maturation rate of oocytes from follicles with the same size regardless of
      cumulus morphology. In contrast, oocytes that had cumulus cells with good
      membrane integrity showed a higher maturation rate (93.8%) than oocytes with poor
      cumulus integrity (76.9%) in large follicles (p < 0.05). We conclude that
      evaluation of membrane integrity of cumulus cells by propidium iodide staining
      can be used to predict the maturational competence of oocytes.

PMID- 21729379
TI  - Secretion profiles from in vitro cultured follicles, isolated from fresh
      prepubertal and adult mouse ovaries or frozen-thawed prepubertal mouse ovaries.
AB  - In vitro folliculogenesis could be a new technology to produce mature oocytes
      from immature follicles that have been isolated from cryopreserved or fresh
      ovarian tissue. This technique could also be a tool for evaluation of oocyte
      quality and/or for determination of follicular parameters during follicular
      growth. Our objective was to characterize in mice the secretion profiles of
      follicles that had been isolated mechanically during in vitro follicular growth
      and in relation to the growth curve. Early preantral follicles from fresh
      prepubertal and adult mouse ovaries or frozen-thawed prepubertal mouse ovaries
      were cultured individually in microdrops under oil for 12 days. Each day, two
      perpendicular diameters of the follicles were measured. From day-3 to day-12 of
      culture, culture medium was collected and preserved for determination of inhibin
      B, anti-Mullerian hormone (AMH) and estradiol levels. At the end of the culture,
      after maturation, the status of the oocyte was evaluated. Follicular growth and
      their individual hormone production did not always correlate. Inhibin B was never
      secreted from follicles of less than 200 MUm diameter, whether the follicles were
      examined when fresh or after freezing-thawing. Estradiol secretion was never
      observed in frozen-thawed follicles. AMH was mainly secreted between day-3 and
      day-9. Despite similar morphological aspects at the start of culture, follicles
      selected for in vitro folliculogenesis were found to be heterogeneous and
      differed in their ability to grow and to produce hormones, even if they had
      similar growth curves. Follicles from frozen-thawed ovaries developed slowly and
      produced fewer hormones than freshly collected follicles.

PMID- 21729380
TI  - An abattoir-based study on the prevalence of hydatidosis in livestock in Mashhad,
      Iran.
AB  - A 6-year (2004-2010) retrospective study was carried out to determine the
      prevalence of hydatidosis in livestock slaughtered in Mashhad abattoir, Mashhad,
      in north-eastern Iran and the capital of Khorasan province. Between 20 March 2004
      and 19 March 2010, 5,131,485 animals (411,163 cattle; 4,547,618 sheep; 172,704
      goats) were slaughtered in the study area and 388,399 (7.5%) livers and 1,139,529
      (22.2%) lungs were discarded. Hydatidosis was responsible for 4% and 6.5% of
      total livers and lungs inspected, respectively. Of the cattle livers and lungs
      inspected over the survey period, 5.5% and 7.9% were condemned, respectively,
      because they held hydatid cysts. The corresponding values for livers and lungs of
      sheep (2%, 4%) and of goats (4.5%, 7.8%), respectively, were also condemned due
      to hydatidosis. Data showed a prominent seasonal pattern for hydatidosis. Liver
      condemnations due to hydatidosis were higher in winter and autumn for cattle and
      sheep, respectively, whereas lung condemnations were higher in summer for sheep
      and cattle. In goats, liver and lung condemnations were higher in winter. This
      could be attributed to various factors, such as sources of slaughtered animals,
      changes in management practice and ecological factors. The present survey
      provides baseline data for the future monitoring of this potentially important
      parasitic disease in the region.

PMID- 21729381
TI  - First report of Troglotrema acutum (Digenea, Troglotrematidae) in the Eurasian
      badger Meles meles in the Iberian Peninsula and presumptive lesions caused in the
      host.
AB  - A total of 109 badger Meles meles skulls from Catalonia (north-eastern Iberian
      Peninsula) were studied for helminths. The tremadode Troglotrema acutum is
      reported here for the first time in the Eurasian badger in the Iberian Peninsula
      and southern Europe. Three methodologies were used to detect this trematode: an
      examination for surface lesions, axial computed tomography and fresh skull
      dissection. The damage caused in the affected skulls is described, along with
      details regarding the use of computed tomography to detect hyperostosis, leakage
      in the sinus structure and bone surface erosion in the affected skulls.

PMID- 21729382
TI  - High levels of Schistosoma mansoni infections among schoolchildren in central
      Sudan one year after treatment with praziquantel.
AB  - A longitudinal study was conducted to evaluate the impact of praziquantel (PZQ)
      for the treatment of Schistosoma mansoni infection among schoolchildren in Al
      Gunaid in Central Sudan. A cohort of schoolchildren (6-15 years of age) was
      investigated before and 1 year after treatment with a single dose of PZQ 40
      mg/kg. Parasitological examinations for S. mansoni were performed before and
      after treatment, and prevalence and intensity of infection were analysed. Of 2741
      schoolchildren recruited from six elementary schools at baseline, 2521 were
      successfully traced and re-examined at follow-up, with two complete sets of
      longitudinal parasitological data on S. mansoni. Boys showed significantly higher
      prevalence of S. mansoni infection than girls. A single dose of PZQ reduced the
      overall prevalence of S. mansoni infection by 36.7% (from 59.1 to 37.4%) and the
      intensity of infection by 41.1% (from 116.7 to 68.7 eggs per gram of stool) 1
      year after treatment. The reduction in prevalence was significantly higher among
      the group of children with heavy infections (by 76.1%, from 6.7 to 1.6%) and
      among girls (by 54.1%, 42.3 to 19.4%) at 1 year after treatment. Thus, in spite
      of a significant reduction in the prevalence and intensity of S. mansoni
      infection 1 year after PZQ treatment, the prevalence of the disease was still
      high and further research is needed on this topic.

PMID- 21729383
TI  - Worm therapy: for or against?
AB  - This article succinctly reviews the weight of evidence supporting worm therapy,
      and asks the question whether the evidence is sufficient to support the use of
      parasitic worms as investigational medicinal products.

PMID- 21729384
TI  - P-glycoproteins of Haemonchus contortus: development of real-time PCR assays for
      gene expression studies.
AB  - P-glycoproteins (P-gps) are proteins that function as efflux pumps, removing
      lipophilic xenobiotic compounds from cells. There is evidence that P-gps play a
      role in the resistance of parasitic nematodes to anthelmintic drugs such as
      benzimidazoles and macrocyclic lactones. As anthelmintic resistance becomes more
      common, it is important to identify candidate resistance genes with the aim of
      understanding the molecular basis of resistance, and of developing assays to
      detect these resistance-associated changes. We identified several sequences from
      the genome of the parasite Haemonchus contortus with convincing homology to the
      known P-gp coding genes of the model nematode Caenorhabditis elegans. Nine of
      these sequences were successfully amplified by polymerase chain reaction (PCR)
      and shown to be most similar to the C. elegans sequences for pgp-1, pgp-2, pgp-3,
      pgp-4, pgp-9, pgp-10, pgp-11, pgp-12 and pgp-14. These partial P-gp sequences
      from H. contortus were used to design and optimize a quantitative real-time PCR
      assay to investigate potential changes in the expression levels of P-gp
      transcripts associated with drug resistance. No significant changes in P-gp mRNA
      expression levels were found in a rapidly selected ivermectin-resistant parasite
      isolate compared to its drug-sensitive parent, but the assay has the potential to
      be used on other isolates in the future to further investigate resistance
      associated changes in P-gp gene expression.

PMID- 21729385
TI  - Seroprevalence of Taenia solium infections in Croatian patients presenting with
      epilepsy.
AB  - Epilepsy is one of the most common neurological disorders, while
      neurocysticercosis caused by Taenia solium infection of the central nervous
      system currently represents the leading cause of secondary epilepsy in Central
      and South America, East and South Asia, and sub-Saharan Africa. As a result of
      increased migration from these endemic regions, neurocysticercosis and subsequent
      epilepsy are becoming a growing public health problem in developed countries as
      well. In order to determine the prevalence of T. solium infection in patients
      with epilepsy in Croatia, a retrospective serological study was conducted. A
      total of 770 serum samples were tested for the presence of T. solium IgG
      antibodies using a commercial qualitative enzyme immunoassay. The Western blot
      technique was used as a confirmatory test for the diagnosis. The overall
      seroprevalence rate of T. solium infection in patients with clinically proven
      epilepsy was 1.5%. Although the results have shown that infection with this
      tapeworm is rare in Croatia, this study hopes to increase awareness about the
      importance of preventive measures and benefits of accurate and timely diagnosis.
      Intervention measures for infection control are crucial, namely sanitation
      improvement, control of domestic pig-breeding, detailed meat inspection,
      detection and treatment of tapeworm carriers, hand washing and health education.

PMID- 21729386
TI  - Diversity and distribution of nematodes associated with terrestrial slugs in the
      Western Cape Province of South Africa.
AB  - A survey of nematodes associated with native and introduced species of
      terrestrial slugs was conducted in the Western Cape Province of South Africa, in
      order to gather new data regarding diversity and distribution. A total of 521
      terrestrial slugs were collected from 35 localities throughout the Western Cape.
      All slugs were dissected and examined for the presence of internal nematodes.
      Extracted nematodes were identified using a combination of molecular (18S rRNA
      gene sequencing) and morphological techniques. Nematodes were found parasitizing
      slugs at 14 of the 35 sites examined, amounting to 40% of sample sites. Of all
      slugs, 6% were infected with nematodes. A total of seven species of nematode were
      identified in the province, including Agfa flexilis, Angiostoma sp.,
      Phasmarhabditis sp. SA1, Phasmarhabditis sp. SA2, Caenorhabditis elegans,
      Panagrolaimus sp. and Rhabditis sp. Of these species, four were thought to be
      parasitic to slugs (A. flexilis, Angiostoma sp., Phasmarhabditis sp. SA1 and
      Phasmarhabditis sp. SA2), as opposed to forming necromenic or phoretic
      associations. Three new species of slug-parasitic nematode were identified during
      this study (Angiostoma sp., Phasmarhabditis sp. SA1 and Phasmarhabditis sp. SA2).

PMID- 21729387
TI  - Platynosomum fastosum-induced chronic intrahepatic cholangitis and Spirometra
      spp. infections in feral cats from Grand Cayman.
AB  - The occurrence of platynosomiasis and intestinal sparganosis is described in
      feral cats from Grand Cayman, Cayman Islands. Spirometra spp. was observed within
      the intestine of 18.18% (10/55) of cats; 1.18% (1/55) of cats demonstrated gross
      and histological manifestation of parasitism by Platynosomum fastosum, but 14.5%
      (8/55) of cats had the characteristic pathological manifestations of P. fastosum
      induced intrahepatic cholangitis without the concomitant presence of the
      intraductal trematode. Combined parasitism (Spirometra spp. and P. fastosum) was
      observed in 9.09% (5/55) of feral cats. Significant pathological findings were
      only associated with the hepatic fluke, P. fastosum, and were grossly
      characterized by moderate hepatomegaly with enlarged and dilated bile ducts.
      Examples of cestodes with morphological features characteristic of Spirometra
      spp. were observed within the small intestine without any associated pathological
      lesion. The histopathological evaluation of liver fragments revealed chronic
      intrahepatic cholangitis with and without the associated intraductal trematode,
      and was characterized by marked periductal fibrosis, adenomatous proliferation of
      bile duct epithelium, dilation of intrahepatic bile ducts and portal
      accumulations of inflammatory cells. The occurrence of the cestode in feral cats
      coupled with factors that are unique to Grand Cayman makes this island the ideal
      location for sporadic cases of human sparganosis.

PMID- 21729388
TI  - Liver enzymes and blood metabolites in a population of free-ranging red deer
      (Cervus elaphus) naturally infected with Fascioloides magna.
AB  - We investigated the effects of Fascioloides magna infection on the serum
      biochemistry values of the naturally infected red deer population in eastern
      Croatia. The investigation was performed on 47 red deer with F. magna infection
      confirmed patho-anatomically in 27 animals (57.4%). Fibrous capsules and
      migratory lesions were found in 14 deer while only fibrous capsules without
      migratory lesions were found in 13 deer. In 13 deer both immature and mature
      flukes were found, in 5 deer only immature flukes were found and in 9 deer only
      mature flukes were found. Fascioloides magna infected deer with fibrous capsules
      and migratory lesions had significantly higher values for lactate dehydrogenase
      (LDH), glutamate dehydrogenase (GLDH) and globulin, and lower values for
      albumin/globulin ratio and glucose compared to uninfected deer. Fascioloides
      magna infected deer with fibrous capsules without the presence of migratory
      lesions had higher values for alanine aminotransferase (ALT) and globulin, and
      lower values for albumin/globulin ratio and glucose, than the uninfected deer.
      The number of immature flukes was positively correlated with values of aspartate
      aminotransferase (AST), gamma-glutamyltransferase (GGT), LDH, GLDH, urea and
      triglycerides. The number of migratory lesions was positively correlated with
      GGT, GLDH, globulin and urea values. The creatinine value was positively
      correlated with the number of mature flukes. The trial showed that F. magna
      infection causes significant changes in serum biochemistry. Moreover, these
      changes do not completely resemble changes following F. hepatica infection.
      Further investigation of changes in liver enzymes and other serum metabolites in
      controlled, experimentally induced fascioloidosis in red deer is needed to better
      understand the pathogenesis of F. magna.

PMID- 21729389
TI  - The effect of anti-Anisakis simplex antibody levels on C3 and C4 complement
      components in human sera.
AB  - Previously, an in vitro effect was observed on the complement system not only of
      the excretory-secretory products but also of somatic antigens from L3 Anisakis
      simplex larvae. In the present work the effect of anti-A. simplex specific
      antibodies on C3 and C4 levels in human sera was investigated. Up to 309 samples
      of sera were tested to determine levels of C3 and C4 and anti-A. simplex
      antibodies, including immunoglobulins IgG, IgM, IgA and IgE. Significant
      differences were observed between levels of C3 and C4 and all immunoglobulins
      except for IgE. In the case of immunoglobulins, the probability that an anti-A.
      simplex positive subject has a C3 deficiency was 3.8 times higher than a subject
      without specific antibodies. In conclusion, an association between elevated
      levels of anti-A. simplex antibodies and C3 and C4 deficiency was demonstrated.

PMID- 21729390
TI  - The occurrence of Dirofilaria immitis, Borrelia burgdorferi, Ehrlichia canis and
      Anaplasma phagocytophium in dogs in China.
AB  - A survey of the occurrence of Dirofilaria immitis, Borrelia burgdorferi,
      Ehrlichia canis and Anaplasma phagocytophium in dogs was undertaken in the
      People's Republic of China between October 2008 and October 2009. A total of 600
      blood samples were taken from dogs in four cities in China: 300 in Beijing, 150
      in Shenzhen, 30 in Shanghai and 120 in Zhengzhou. All samples were tested for the
      heartworm antigen and antibodies of canine B. burgdorferi, E. canis and A.
      phagocytophium by using the canine SNAP(r) 4Dx(r) test kit. The occurrence of D.
      immitis, B. burgdorferi, E. canis and A. phagocytophium was 1.17% (7/600), 0.17%
      (1/600), 2.17% (13/600) and 0.5% (3/600), respectively. In Shenzhen city 2%
      (3/150), 8.67% (13/150) and 2% (3/150) of samples were positive for D. immitis,
      E. canis and A. phagocytophium, respectively. The occurrence of heartworm antigen
      was 0.33% (1/300) in Beijing, 2.00% (3/150) in Shenzhen, 3.33% (1/30) in Shanghai
      and 1.67% (2/120) in Zhengzhou. We found E. canis and A. phagocytophium only at
      one site, Shenzhen, while the only occurrence of B. burgdorferi was at Beijing.
      In conclusion, the dog population in China is at potential risk for D. immitis,
      B. burgdorferi, E. canis and A. phagocytophium infection, the risk being
      especially high in southern China.

PMID- 21729391
TI  - Morpho-functional specialization of the branching sporocyst of Prosorhynchoides
      borealis Bartoli, Gibson & Bray, 2006 (Digenea, Bucephalidae).
AB  - Sporocysts of Prosorhynchoides borealis were obtained from the marine bivalves
      Abra prismatica and studied using transmission electron microscopy. The sporocyst
      body consists of a mass of branching and intertwining hollow tubules that ramify
      through the host's digestive gland and gonads. This study investigated the
      ultrastructure of the sporocyst branches which comprise alternate distended areas
      (brood chambers) with a relatively thin body wall, narrower portions with a
      thicker body wall (constricted areas) and terminal regions. Pronounced
      differences between these areas were revealed in the structure of their tegument
      and body cavity lining, as well as in the cellular composition of the
      subtegumental layers. Body wall composition in distended areas was consistent
      with the specialization for cercarial nurture in the brood chambers. The
      structure of the constrictions suggested a dual role of nutrient absorption and
      physical separation of adjacent brood chambers. Two types of terminal region were
      identified, one specialized for the investigation and penetration of host tissues
      and the other, in which the germinal cells are formed, for cercarial production.
      The overall structure of the sporocyst branches helps explain why this linear
      modular system, i.e. brood chambers and constrictions continuously growing into
      the host tissue, enables the sporocyst's long-term existence and can continuously
      produce cercariae in numbers comparable with those produced by rediae and/or
      daughter sporocyst infrapopulations in other digeneans. The origin of the nuclei
      in the outer tegumental layer of some branching bucephalid sporocysts is also
      discussed.

PMID- 21729392
TI  - Spatial clustering and longitudinal variation of Anopheles darlingi (Diptera:
      Culicidae) larvae in a river of the Amazon: the importance of the forest fringe
      and of obstructions to flow in frontier malaria.
AB  - Deforestation has been linked to a rise in malaria prevalence. In this paper, we
      studied longitudinally 20 spots, including forested and deforested portions of a
      temporary river in a malarigenous frontier zone. Larval habitat parameters
      influencing distribution of Anopheles darlingi (Diptera: Culicidae) larvae were
      studied. We observed that larvae were clustered in forested-deforested
      transitions. For the first time in the literature, it was verified that
      parameters determining larval distribution varied from deforested to forested
      areas. The proximity to human dwellings was also a significant factor determining
      distribution, but larvae was most importantly associated with a previously
      undescribed parameter, the presence of small obstructions to river flow, such as
      tree trunks within the river channel, which caused pooling of water during the
      dry season ('microdams'). In deforested areas, the most important factor
      determining distribution of larvae was shade (reduced luminance). Larvae were
      absent in the entire studied area during the wet season and present in most sites
      during the dry season. During the wet-dry transition, larvae were found sooner in
      areas with microdams, than in other areas, suggesting that flow obstruction
      prolongs the breeding season of An. darlingi. Adult mosquito densities and
      malaria incidence were higher during the dry season. Our data correlate well with
      the published literature, including the distribution of malaria cases near the
      forest fringes, and has permitted the creation of a model of An. darlingi
      breeding, where preference for sites with reduced luminance, human presence and
      microdams would interact to determine larval distribution.

PMID- 21729393
TI  - Phenological diversity in the interactions between winter moth (Operophtera
      brumata) larvae and parasitoid wasps in sub-arctic mountain birch forest.
AB  - Population cycles of the winter moth (Operophtera brumata) in sub-arctic coastal
      birch forests show high spatiotemporal variation in amplitude. Peak larval
      densities range from levels causing little foliage damage to outbreaks causing
      spatially extensive defoliation. Moreover, outbreaks typically occur at or near
      the altitudinal treeline. It has been hypothesized that spatiotemporal variation
      in O. brumata cycle amplitude results from climate-induced variation in the
      degree of phenological matching between trophic levels, possibly between moth
      larvae and parasitoids. The likelihood of mismatching phenologies between larvae
      and parasitoids is expected to depend on how specialized parasitoids are, both as
      individual species and as a guild, to attacking specific larval developmental
      stages (i.e. instars). To investigate the larval instar-specificity of
      parasitoids, we studied the timing of parasitoid attacks relative to larval
      phenology. We employed an observational study design, with sequential sampling
      over the larval period, along an altitudinal gradient harbouring a pronounced
      treeline outbreak of O. brumata. Within the larval parasitoid guild, containing
      seven species groups, the timing of attack by different groups followed a
      successional sequence throughout the moth's larval period and each group attacked
      1-2 instars. Such phenological diversity within parasitoid guilds may lower the
      likelihood of climate-induced trophic mismatches between victim populations and
      many/all of their enemies. Parasitism rates declined with increasing altitude for
      most parasitoid groups and for the parasitoid guild as a whole. However, the
      observed spatiotemporal parasitism patterns provided no clear evidence for or
      against altitudinal mismatch between larval and parasitoid phenology.

PMID- 21729394
TI  - Enantiomeric selectivity in behavioural and electrophysiological responses of
      Aedes aegypti and Culex quinquefasciatus mosquitoes.
AB  - 1-Octen-3-ol is a kairomone for many haematophagous insects including mosquitoes.
      Numerous studies have examined the effects of racemic 1-octen-3-ol; however, few
      studies have investigated the role of individual enantiomers in relation to
      mosquito attraction. In the present study, we investigated the behavioural and
      electrophysiological responses of two mosquito species, Aedes aegypti and Culex
      quinquefasciatus, to individual enantiomers and mixtures of 1-octen-3-ol,
      employing a laboratory Y-tube olfactometer and single sensillum recordings. The
      olfactory receptor neurons of both Ae. aegypti and Cx. quinquefasciatus had a
      significantly higher response to the (R)-1-octen-3-ol enantiomer compared to the
      (S)-1-octen-3-ol enantiomer at 10-9 g MUl-1 to 10-6 g MUl-1. Behaviourally, Ae.
      aegypti was more responsive to the (R)-1-octen-3-ol enantiomer, showing an
      increase in flight activity and relative attraction compared to Cx.
      quinquefasciatus. The (R)-1-octen-3-ol enantiomer caused an increase in
      activation for Cx. quinquefasciatus. However, the most notable effect was from an
      (R:S)-1-octen-3-ol mixture (84:16) that caused significantly more mosquitoes to
      sustain their flight and reach the capture chambers (demonstrated by a reduced
      non-sustained flight activity), suggesting that it may have a behaviourally
      excitatory effect. For Cx. quinquefasciatus, a reduced relative attraction
      response was also observed for all treatments containing the (R)-1-octen-3-ol
      enantiomer, either on its own or as part of a mixture, but not with the (S)-1
      octen-3-ol enantiomer. This is the first time enantiomeric selectivity has been
      shown for Ae. aegypti using electrophysiology in vivo. The implications of these
      results for exploitation in mosquito traps are discussed.

PMID- 21729395
TI  - Physiological trade-offs of forming maggot masses by necrophagous flies on
      vertebrate carrion.
AB  - Necrophagous flies that colonize human and animal corpses are extremely efficient
      at locating and utilizing carrion. Adult flies deposit eggs or larvae on the
      ephemeral food resource, which signals the beginning of intense inter- and intra
      species competition. Within a short period of time after egg hatch, large larval
      aggregations or maggot masses form. A period of intense larval feeding ensues
      that will culminate with consumption/decomposition of all soft tissues associated
      with the corpse. Perhaps the most distinctive feature of these feeding
      aggregations is heat production; that is, the capacity to generate internal heat
      that can exceed ambient temperatures by 30 degrees C or more. While observations
      of maggot mass formation and heat generation have been described in the research
      literature for more than 50 years, our understanding of maggot masses,
      particularly the physiological ecology of the aggregations as a whole, is
      rudimentary. In this review, an examination of what is known about the formation
      of maggot masses is presented, as well as arguments for the physiological
      benefits and limitations of developing in feeding aggregations that, at times,
      can represent regions of intense competition, overcrowded conditions, or a
      microclimate with elevated temperatures approaching or exceeding proteotoxic
      stress levels.

PMID- 21729396
TI  - Cloning and characterization of mariner-like elements in the soybean aphid, Aphis
      glycines Matsumura.
AB  - Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is currently the
      most important insect pest of soybean (Glycine max (L.) Merr.) in the United
      States and causes significant economic damage worldwide, but little is known
      about the aphid at the molecular level. Mariner-like transposable elements (MLEs)
      are ubiquitous within the genomes of arthropods and various other invertebrates.
      In this study, we report the cloning of MLEs from the soybean aphid genome using
      degenerate PCR primers designed to amplify conserved regions of mariner
      transposases. Two of the ten sequenced clones (designated as Agmar1 and Agmar2)
      contained partial but continuous open reading frames, which shared high levels of
      homology at the protein level with other mariner transposases from insects and
      other taxa. Phylogenetic analysis revealed Agmar1 to group within the irritans
      subfamily of MLEs and Agmar2 within the mellifera subfamily. Southern blot
      analysis and quantitative PCR analysis indicated a low copy number for Agmar1
      like elements within the soybean aphid genome. These results suggest the presence
      of at least two different putative mariner-like transposases encoded by the
      soybean aphid genome. Both Agmar1 and Agmar2 could play influential roles in the
      architecture of the soybean aphid genome. Transposable elements are also thought
      to potentially mediate resistance in insects through changes in gene
      amplification and mutations in coding sequences. Finally, Agmar1 and Agmar2 may
      represent useful genetic tools and provide insights on A. glycines adaptation.

PMID- 21729397
TI  - Differentiation of Solenopsis invicta social forms using high resolution melt
      PCR.
AB  - Solenopsis invicta Buren (red imported fire ant) are invasive pests that have the
      capability of major destructive impacts on lifestyle, ecology and economy.
      Control of this species is dependent, in part, upon ability to estimate the
      potential spread from newly discovered nests. The potential for spread and the
      spread characteristics differ between monogyne and polygyne social forms. Prior
      to this study, differentiation of the two social forms in laboratory test samples
      commonly used a method involving restriction endonuclease digestion of an
      amplified Gp-9 fragment. Success of this assay is limited by the quality of DNA,
      which in the field-collected insects may be affected by temporary storage in
      unfavourable conditions. Here, we describe an alternative and highly objective
      assay based upon a high resolution melt technique following preamplification of a
      significantly shorter Gp-9 fragment than that required for restriction
      endonuclease digestion. We demonstrate the application of this assay to a S.
      invicta incursion in Queensland, Australia, using field samples from which DNA
      may be partially degraded. The reductions in hands-on requirements and overall
      duration of the assay underpin its suitability for high-throughput testing.

PMID- 21729398
TI  - Differential contribution of cognitive and psychomotor functions to the age
      related slowing of speech production.
AB  - Healthy elderly adults are slower to initiate and produce speech. However, the
      sources of the slowing remain poorly understood. The present study evaluates to
      which extent psychomotor and cognitive changes influence age-related slowing in
      speech generation. Four verbal tasks varying in degree of difficulty and
      cognitive demands were used to evaluate 30 young and 30 healthy elderly. Speed of
      word production was measured by reaction times and pronunciation durations.
      Stroop test and Digits backwards were used as cognitive predictors while the
      Purdue Pegboard and Finger Tapping were used as psychomotor predictors. The
      relative contribution of cognitive and psychomotor functioning was evaluated by
      hierarchical regression analyses and based on the processing speed hypothesis.
      Results showed that Vocabulary and psychomotor execution significantly explained
      a portion of the variance in RTs depending on type of verbal task. These
      variables explained 36% of the total variance in reading, 26% in naming, 31% in
      phonemic fluency and 47% in semantic fluency. Also, Vocabulary and psychomotor
      functions strongly predicted pronunciation speed. Conversely, tests related to
      executive functions and working memory were not significant predictors. These
      data demonstrate the importance of the interplay between Vocabulary and
      psychomotor decline on speed of language production among healthy elderly adults.

PMID- 21729399
TI  - The relation between depressive symptoms and semantic memory in amnestic mild
      cognitive impairment and in late-life depression.
AB  - Semantic deficits have been documented in the prodromal phase of Alzheimer's
      disease, but it is unclear whether these deficits are associated with non
      cognitive manifestations. For instance, recent evidence indicates that cognitive
      deficits in elders with amnestic mild cognitive impairment (aMCI) are modulated
      by concomitant depressive symptoms. The purposes of this study were to (i)
      investigate if semantic memory impairment in aMCI is modulated according to the
      presence (aMCI-D group) or absence (aMCI group) of depressive symptoms, and (ii)
      compare semantic memory performance of aMCI and aMCI-D groups to that of patients
      with late-life depression (LLD). Seventeen aMCI, 16 aMCI-D, 15 LLD, and 26
      healthy control participants were administered a semantic questionnaire assessing
      famous person knowledge. Results showed that performance of aMCI-D patients was
      impaired compared to the control and LLD groups. However, in the aMCI group
      performance was comparable to that of all other groups. Overall, these findings
      suggest that semantic deficits in aMCI are somewhat associated with the presence
      of concomitant depressive symptoms. However, depression alone cannot account
      solely for the semantic deficits since LLD patients showed no semantic memory
      impairment in this study. Future studies should aim at clarifying the association
      between depression and semantic deficits in older adults meeting aMCI criteria.
      (JINS, 2011, 17, 865-874).

PMID- 21729400
TI  - Cognitive correlates of functional performance in older adults: comparison of
      self-report, direct observation, and performance-based measures.
AB  - Neuropsychologists are often asked to answer questions about the effects of
      cognitive deficits on everyday functioning. This study examined the relationship
      between and the cognitive correlates of self-report, performance-based, and
      direct observation measures commonly used as proxy measures for everyday
      functioning. Participants were 88 community-dwelling, cognitively healthy older
      adults (age 50-86 years). Participants completed standardized neuropsychological
      tests and questionnaires, and performed eight activities of daily living (e.g.,
      water plants, fill a medication dispenser) while under direct observation in a
      campus apartment. All proxy measures of everyday function were sensitive to the
      effects of healthy cognitive aging. After controlling for age, cognitive
      predictors explained a unique amount of the variance for only the performance
      based behavioral simulation measure (i.e., Revised Observed Tasks of Daily
      Living). The self-report instrumental activities of daily living (IADL) and the
      performance-based everyday problem-solving test (i.e., EPT) did not correlate
      with each other; however, both were unique predictors of the direct observation
      measure. These findings suggest that neuropsychologists must be cautious in
      making predictions about the quality of everyday activity completion in
      cognitively healthy older adults from specific cognitive functions. The findings
      further suggest that a self-report of IADLs and the performance-based EPT may be
      useful measures for assessing everyday functional status in cognitively healthy
      older adults.

PMID- 21729401
TI  - Strategic manipulations for associative memory and the role of verbal processing
      abilities in schizophrenia.
AB  - Individuals with schizophrenia demonstrate episodic memory (EM) deficits and
      abnormal EM-related brain activity. Experimental encoding manipulations
      significantly benefit memory performance in schizophrenia, suggesting that a
      strategic processing deficit may contribute to memory impairment. However, few
      studies have investigated the combined effects of encoding and retrieval
      strategies on EM in schizophrenia. The current study examined the impact of
      encoding and retrieval strategies on associative memory and brain activity in
      schizophrenia. We also assessed the role of verbal processing ability in response
      to strategic memory interventions in schizophrenia. Behavioral and functional
      neuroimaging data were collected from 23 participants with schizophrenia and 24
      comparison subjects while performing associative memory encoding and recall
      tasks. Behaviorally, both schizophrenia participants and controls benefited from
      memory strategies and showed significant associations between verbal processing
      ability and recall. Additionally, among schizophrenia participants, encoding
      strategy use was associated with enhanced brain activity in multiple brain areas.
      Schizophrenia participants also demonstrated significant associations between
      verbal processing ability and encoding-related brain activity in prefrontal
      cortex. Findings suggest that memory performance and brain activity in
      schizophrenia can be enhanced via strategic manipulations, and individual
      differences in cognitive abilities in schizophrenia can affect behavioral and
      neurobiological responses to strategic memory interventions.

PMID- 21729402
TI  - Self-awareness of motor dysfunction in patients with Huntington's disease in
      comparison to Parkinson's disease and cervical dystonia.
AB  - Individuals suffering from Huntington's disease (HD) have been shown to present
      with poor self-awareness of a variety of symptoms. The aim of this study was to
      better assess the self-awareness of motor symptoms and activities of daily living
      (ADL) impairment in HD, in comparison to Parkinson's disease (PD) and cervical
      dystonia (CD). In particular, the anosognosia/anosodiaphoria of involuntary
      movements has been investigated. Self-awareness was tested in 23 patients with HD
      by comparing patient and caregiver ratings in reference to clinical control
      groups (25 PD with dyskinesias, PDdys; 21 PD without dyskinesias, PDndys; and 20
      with CD). Patients were assessed neurologically by relevant rating scales. Self
      awareness was tested using a scale based on 15 films demonstrating 3 types of
      motor symptoms (chorea/dyskinesias, parkinsonism, torticollis) as well as the
      Self-Assessment Parkinson's Disease Disability Scale. General cognitive status,
      verbal learning, cognitive control, and mood were also analyzed. Our results
      indicate that self-awareness of choreic movements was affected more severely in
      HD than in PDdys, despite comparable cognitive status. Patient-proxy agreement on
      ADL impairment was roughly similar in all clinical groups. The results are
      discussed in the context of orbitofrontal-limbic pathology as a potential trigger
      of anosognosia/anosodiaphoria in individuals with HD.

PMID- 21729403
TI  - Memory transformation and systems consolidation.
AB  - With time and experience, memories undergo a process of reorganization that
      involves different neuronal networks, known as systems consolidation. The
      traditional view, as articulated in standard consolidation theory (SCT), is that
      (episodic and semantic) memories initially depend on the hippocampus, but
      eventually become consolidated in their original forms in other brain regions. In
      this study, we review the main principles of SCT and report evidence from the
      neuropsychological literature that would not be predicted by this theory. By
      comparison, the evidence supports an alternative account, the transformation
      hypothesis, whose central premise is that changes in neural representation in
      systems consolidation are accompanied by corresponding changes in the nature of
      the memory. According to this view, hippocampally dependent, episodic, or context
      specific memories transform into semantic or gist-like versions that are
      represented in extra-hippocampal structures. To the extent that episodic memories
      are retained, they will continue to require the hippocampus, but the hippocampus
      is not needed for the retrieval of semantic memories. The transformation
      hypothesis emphasizes the dynamic nature of memory, as well as the underlying
      functional and neural interactions that must be taken into account in a
      comprehensive theory of memory.

PMID- 21729404
TI  - The temporal relationship between depression, anxiety, and functional status
      after traumatic brain injury: a cross-lagged analysis.
AB  - Poor functional status and high rates of anxiety and depression have been
      reported in individuals who have sustained a traumatic brain injury (TBI).
      However, it is unclear whether psychiatric disorders after TBI are a cause or a
      consequence of functional limitations. The current study aimed to investigate the
      temporal relationship between anxiety, depression and functional impairment
      following TBI. The study has a prospective, longitudinal single-group design.
      Anxiety and depression, assessed using the Structured Clinical Interview for DSM
      IV, and functional changes, assessed with the Glasgow Outcome Scale-Extended,
      were measured six and 12 months post-injury in 122 individuals who had sustained
      a TBI (79% male, mean age 35 years, mean duration of post-traumatic amnesia 24
      days, mean Glasgow Coma Scale score 9.2). Cross-lagged analyses were conducted
      within a structural equation modelling framework. Functional changes six months
      post-injury predicted depression and anxiety one year after the injury. Anxiety
      and depression, in turn, were not predictive of later functional status. This
      study adds to our understanding of the temporal relationship between depression,
      anxiety and functional status after TBI. The results indicate the importance of
      supporting brain injured individuals in coping with the functional consequences
      of their injury in order promote psychological well-being.

PMID- 21729405
TI  - The self-imagination effect: benefits of a self-referential encoding strategy on
      cued recall in memory-impaired individuals with neurological damage.
AB  - Knowledge of oneself is preserved in many memory-impaired individuals with
      neurological damage. Therefore, cognitive strategies that capitalize on
      mechanisms related to the self may be particularly effective at enhancing memory
      in this population. The present study investigated the effect of "self
      imagining," imagining an event from a personal perspective, on short and long
      delayed cued recall in memory-impaired individuals with neurological damage.
      Sixteen patients intentionally encoded word pairs under four separate conditions:
      visual imagery, semantic elaboration, other person imagining, and self-imagining.
      The results revealed that self-imagining led to better performance than other
      imagining, semantic elaboration, and visual imagery. Furthermore, the "self
      imagination effect" (SIE) was preserved after a 30-min delay and was independent
      of memory functioning. These findings indicate that self-imagining provides a
      mnemonic advantage in brain-injured individuals, even those with relatively poor
      memory functioning, and suggest that self-imagining may tap into mnemonic
      mechanisms related to the self.

PMID- 21729406
TI  - Functions of the frontal lobes: relation to executive functions.
AB  - Proceeding from the assumptions that specific frontal regions control discrete
      functions and that very basic cognitive processes can be systematically
      manipulated to reveal those functions, recent reports have demonstrated
      consistent anatomical/functional relationships: dorsomedial for energization,
      left dorsolateral for task setting, and right dorsolateral for monitoring. There
      is no central executive. There are, instead, numerous domain general processes
      discretely distributed across several frontal regions that act in concert to
      accomplish control. Beyond these functions, there are two additional "frontal"
      anatomical/functional relationships: ventral-medial/orbital for emotional and
      behavioral regulation, and frontopolar for integrative-even meta-cognitive
      functions.

PMID- 21729407
TI  - Assessment of cognitive flexibility in anorexia nervosa--self-report or
      experimental measure? A brief report.
AB  - This study investigated the correspondence between self-report and experimental
      measures of cognitive flexibility in individuals with anorexia nervosa (AN) and
      healthy controls (HCs). Ninety-four participants (45 individuals with AN and 49
      HCs) completed the self-report Cognitive Flexibility Scale (CFS) and an
      experimental task, the Brixton Spatial Anticipation Test. The AN group performed
      poorly on both measures of cognitive flexibility compared with HCs. There was no
      significant correlation between the CFS scores and the errors on the Brixton Test
      for both groups. The findings suggest there is poor correspondence between the
      self-report measure of cognitive flexibility and performance on the flexibility
      test. These two assessment tools therefore cannot be used interchangeably to
      assess cognitive flexibility. Flexibility is an important clinical characteristic
      in AN. The results suggest that self-report and behavioral measures can be
      complementary, but cannot be used as an alternative to one another.

PMID- 21729408
TI  - Effects of age, education and gender in the Consortium to Establish a Registry
      for the Alzheimer's Disease (CERAD)-Neuropsychological Assessment Battery for
      Cantonese-speaking Chinese elders.
AB  - BACKGROUND: The Consortium to Establish a Registry for Alzheimer's Disease
      Neuropsychological Assessment Battery (CERAD-NAB) offers information on the
      clinical diagnosis of Alzheimer's disease (AD) and gives a profile of cognitive
      functioning. This study explores the effects of age, education and gender on
      participants' performance on eight subtests in the Chinese-Cantonese version of
      the CERAD-NAB. METHODS: The original English version of the CERAD-NAB was
      translated and content-validated into a Chinese-Cantonese version to suit the
      Hong Kong Chinese population. The battery was administered to 187 healthy
      volunteers aged 60 to 94 years. Participants were excluded if they had
      neurological, medical or psychiatric disorders (including dementia). Stepwise
      multiple linear regression analyses were performed to assess the relative
      contribution of the demographic variables to the scores on each subtest. RESULTS:
      The Cantonese version of CERAD-NAB was shown to have good content validity and
      excellent inter-rater reliability. Stepwise multiple regression analyses revealed
      that performances on seven and four out of eight subtests in the CERAD-NAB were
      significantly influenced by education level and age, respectively. Age and
      education had significant effects on participants' performance on many tests.
      Gender also showed a significant effect on one subtest. CONCLUSIONS: The
      preliminary data will serve as an initial phase for clinical interpretation of
      the CERAD-NAB for Cantonese-speaking Chinese elders.

PMID- 21729409
TI  - The course of neuropsychiatric symptoms in patients with dementia in Norwegian
      nursing homes.
AB  - BACKGROUND: Neuropsychiatric symptoms (NPS) are common in patients with dementia,
      and cause distress for patients. Studies on the prevalence, incidence,
      persistence and resolution of NPS in patients living in nursing homes are sparse.
      The aim of this study was to evaluate the course of NPS in patients with dementia
      living in Norwegian nursing homes. METHODS: 169 patients from seven Norwegian
      nursing homes were assessed five times over a period of 16 months with the
      Neuropsychiatric Inventory (NPI). The severity and the frequency of the NPI were
      analyzed. RESULTS: 91.7% of the patients had at least one clinically significant
      NPS at one or more assessments over the 16 months. Irritability (63.5%),
      agitation (51.0%) and disinhibition (50.0%) had the highest cumulative
      prevalence, while irritability (42.6%), disinhibition (37.8%) and depression
      (31.5%) showed the highest cumulative incidence. Delusion, agitation and
      irritability were enduring symptoms while the other symptoms had high resolution
      rates. The severity of the NPS did not vary significantly over time. CONCLUSION:
      Almost every patient in Norwegian nursing homes had at least one clinically
      significant NPS over 16 months, but individual NPS show a fluctuating course.
      This should influence how we monitor and treat NPS in patients with dementia.

PMID- 21729410
TI  - Caregivers' perspectives on the pre-diagnostic period in early onset dementia: a
      long and winding road.
AB  - BACKGROUND: Recognizing and diagnosing early onset dementia (EOD) can be complex
      and often takes longer than for late onset dementia. The objectives of this study
      are to investigate the barriers to diagnosis and to develop a typology of the
      diagnosis pathway for EOD caregivers. METHODS: Semi-structured interviews with 92
      EOD caregivers were analyzed using constant comparative analysis and grounded
      theory. A conceptual model was formed based on 21 interviews and tested in 29
      additional transcripts. The identified categories were quantified in the whole
      sample. RESULTS: Seven themes emerged: (1) changes in the family member, (2)
      disrupted family life, (3) misattribution, (4) denial and refusal to seek advice,
      (5) lack of confirmation from social context, (6) non-responsiveness of a general
      practitioner (GP), and (7) misdiagnosis. Cognitive and behavioral changes in the
      person with EOD were common and difficult to understand for caregivers. Marital
      difficulties, problems with children and work/financial issues were important
      topics. Confirmation of family members and being aware of problems at work were
      important for caregivers to notice deficits and/or seek help. Other main issues
      were a patient's refusal to seek help resulting from denial and inadequate help
      resulting from misdiagnosis. CONCLUSION: EOD caregivers experience a long and
      difficult period before diagnosis. We hypothesize that denial, refusal to seek
      help, misattribution of symptoms, lack of confirmation from the social context,
      professionals' inadequate help and faulty diagnoses prolong the time before
      diagnosis. These findings underline the need for faster and more adequate help
      from health-care professionals and provide issues to focus on when supporting
      caregivers of people with EOD.

PMID- 21729411
TI  - Reasons why family members become carers and the outcome for the person with
      dementia: results from the CARD study.
AB  - BACKGROUND: Using a representative secondary care survey for the first time, we
      explored family carers' reasons for providing care. We hypothesized that carers
      with a positive rather than negative motivation for caring would be less abusive
      towards the care recipient and more likely to be caring for someone still living
      at home a year later. METHODS: We interviewed 220 consecutively referred dementia
      family/friend carers from UK Community Mental Health Teams. We asked non-spousal
      carers why they were the main carer. Our main outcomes were the revised Modified
      Conflict Tactics Scale scores, measuring abusive behavior by the carer, and
      admission of the person with dementia to a care home. RESULTS: Nineteen (17.1%)
      said they were the main carer due to the high quality of their relationship with
      the care recipient, their willingness to take on or their suitability for the
      carer role. A further 22 (19.8%) said they were the main carer due to other
      potential carers' negative relationship with the care recipient, unwillingness or
      lack of suitability for the role. Carers who gave the latter explanation tended
      to be more anxious at baseline (F = 3.0, p = 0.055), reported higher abusive
      behavior towards the care recipient a year later after controlling for
      sociodemographic variables (t = 2.0, p = 0.05), and their care recipient was more
      likely to be admitted to a care home in the following year (hazards ratio 9.9, p
      = 0.040). CONCLUSIONS: We found preliminary evidence that carers' reasons for
      providing care predict the well-being of the care recipient. Future studies
      involving dementia family carers should consider asking why the main carer
      assumed this role.

PMID- 21729412
TI  - Treatment characteristics of delirium superimposed on dementia.
AB  - BACKGROUND: The course of delirium in patients with dementia who are undergoing
      management of delirium with antipsychotics has not previously been studied. In
      order to investigate the treatment characteristics of patients with delirium
      superimposed on dementia in contrast to delirium in the absence of dementia we
      performed a secondary analysis of our delirium database. METHODS: We collected
      sociodemographic data and medical variables in addition to using the systematic
      rating scales of the Memorial Delirium Assessment Scale (MDAS) and Karnofsky
      Scale of Performance Status (KPS). These data were recorded in the delirium
      database. For this analysis we extracted all data pertaining to patients with
      delirium and dementia (DD) and compared them to those with delirium without
      dementia (i.e. non-demented with delirium; NDD). RESULTS: Out of 111 cases with a
      diagnosis of delirium we acquired 22 cases with a diagnosis of DD and 89 cases
      with NDD. The mean age was significantly different with 77.1 years for DD and
      62.7 years for NDD. The MDAS scores at baseline were significantly higher in DD
      (21.1) compared to NDD (17.6). Over the course of treatment, MDAS scores were
      significantly higher in DD with 11.7 at T3 compared with 7.0 in NDD. After three
      days of management, delirium resolution rates were significantly lower in DD with
      18.2% compared to 53.9% in NDD, and at seven days delirium resolution rates were
      50% and 83% respectively. At the endpoint of the observation period, DD had a
      significantly more pronounced disturbance of consciousness and impairment in the
      cognitive domain. KPS scores were not significantly different between DD and NDD.
      CONCLUSION: In our sample of patients with delirium superimposed on dementia the
      delirium resolution rates were lower than in patients without dementia at one
      week of treatment. The data suggest that when delirium is superimposed on
      dementia the delirium may resolve at a slower rate.

PMID- 21729413
TI  - Neuropsychological correlates of apathy in mild cognitive impairment and
      Alzheimer's disease: the role of executive functioning.
AB  - BACKGROUND: Apathy is a common and important behavioral syndrome in various
      neuropsychiatric diseases, such as mild cognitive impairment (MCI) and
      Alzheimer's disease (AD). So far, only few studies have compared the
      neuropsychological correlates of apathy in patients with MCI and dementia. The
      aim of the current study was to examine the association between apathy and
      neuropsychological functioning in patients with MCI and AD. METHODS: Two-hundred
      and-sixty AD patients and 178 MCI patients visiting the Memory Clinic of the
      Maastricht University Medical Centre participated in the study. Linear regression
      analysis, corrected for age, gender, level of education and depression, was
      performed to reveal cross-sectional associations between apathy and scores on
      neuropsychological tests of memory, attention, psychomotor speed and executive
      functioning. RESULTS: In patients with MCI, apathy was characterized by decreased
      verbal fluency and psychomotor tracking. In AD, patients with apathy differed
      from non-apathetic patients only on a verbal fluency task. CONCLUSION: Apathy is
      related to executive dysfunction in the early phases of cognitive decline. In
      particular, in the prodromal phase of AD, apathy seems to be characterized by
      poor initiating. In the more advanced stages of cognitive deterioration,
      associations between apathy and specific neuropsychological correlates may be
      obscured by the more severe neuropathology. Awareness of apathy in the early
      phase of cognitive impairment may help in early diagnosis of AD.

PMID- 21729414
TI  - Beliefs about medications predict adherence to antidepressants in older adults.
AB  - BACKGROUND: Adherence to treatment is a complex and poorly understood phenomenon.
      This study investigates the relationship between older depressed patients'
      adherence to antidepressants and their beliefs about and knowledge of the
      medication. METHODS: Assessment was undertaken of 108 outpatients over the age of
      55 years diagnosed with depressive disorder and treated for at least four weeks
      with antidepressants. Adherence was assessed using two self-report measures: the
      Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM).
      Potential predictors of adherence investigated included sociodemographic,
      medication and illness variables. In addition, 33 carers were interviewed
      regarding general medication beliefs. RESULTS: 56% of patients reported 80% or
      higher adherence on the GAM. Sociodemographic variables were not associated with
      adherence on the MARS. Specific beliefs about medicines, such as "my health
      depends on antidepressants" (necessity) and being less worried about becoming
      dependant on antidepressants (concern) were highly correlated with adherence.
      General beliefs about medicines causing harm or being overprescribed,
      experiencing medication side-effects and severity of depression also correlated
      with poor adherence. Linear regression with the MARS as the dependent variable
      explained 44.3% of the variance and showed adherence to be higher in subjects
      with healthy specific beliefs who received more information about antidepressants
      and worse with depression severity and autonomic side-effects. CONCLUSIONS: Our
      findings strongly support a role for specific beliefs about medicines in
      adherence. Challenging patients' beliefs, providing information about treatment
      and discussing side-effects could improve adherence. Poor response to treatment
      and medication side-effects can indicate poor adherence and should be considered
      before switching medications.

PMID- 21729415
TI  - Proxy-rated quality of life in Alzheimer's disease: a three-year longitudinal
      study.
AB  - BACKGROUND: The study investigated the change in proxy rated quality of life
      (QoL) of a large cohort of home living patients with Alzheimer's disease (AD)
      over a period of 36 months. METHODS: The sample consisted of 102 patients with
      mild AD and their primary caregivers from the Danish Alzheimer's Disease
      Intervention Study. QoL was assessed with the proxy-rated (primary caregivers)
      Quality of Life in Alzheimer Disease scale (QOL-AD) and the EuroQuol Visual
      Analogue Scale (EQ-VAS) scale. The Cornell Scale for Depression in Dementia
      (CSDD), Alzheimer's Disease Cooperative Study, Activities of Daily living
      Inventory (ADCS-ADL), Mini-Mental State Examination (MMSE) and Neuropsychiatric
      Inventory (NPI-Q) were also applied. Evaluations were conducted at baseline and
      at 12 and 36 months follow-up. RESULTS: There was a significant decline in mean
      QoL assessed by both the QOL-AD and the EQ-VAS (p < 0.001). There were vast
      individual differences in the QoL scores on both scales at 12 and 36 months'
      follow-up. Mean change from baseline in QOL-AD was significantly associated with
      change in CSDD, ADCS-ADL and MMSE scores at 12 months and with ADCS-ADL score at
      36 months. CONCLUSION: QoL is a subjective concept and may not be influenced by
      the degree of cognitive dysfunction. Future studies should investigate the
      factors for individual variations in order to understand the nature of change of
      QoL in AD and the wide variation in QoL scores over time.

PMID- 21729416
TI  - Quality of life in dementia patients: nursing home versus home care.
AB  - BACKGROUND: Care management providing a high quality of life (QoL) is a crucial
      issue in dealing with increasing numbers of dementia patients. Although the
      transition from informal (home-based) care to formal (institutional) care is
      often a function of dementia stage, for those with early dementia there is
      currently no definitive evidence showing that informal or formal care provides a
      higher QoL, particularly where informal care is favored for local cultural
      reasons. This paper outlines the research protocol for a study comparing formal
      and informal care in Malaysia. It seeks to provide evidence regarding which is
      more appropriate and results in higher QoL in early dementia. METHODS: This is a
      quasi-experimental study design involving 224 early dementia patients from both
      nursing home and community settings. Participants will be assessed for cognitive
      severity, QoL, needs, activities of daily living, depression and social
      isolation/connectedness by using the Mini-Mental State Examination (MMSE),
      Cognitive Impairment Scale - 4 items (CIS-4), EUROPE Health Interview Survey
      Quality of Life (WHO8), Assessment of Quality of Life (AQoL8), Camberwell
      Assessment of Need for the Elderly - Short Version (CANE-S), Barthel Index (BI),
      Cornell Scale for Depression (CSDD), Geriatric Depression Scale - 15 items (GDS
      15), and Friendship Scale (FS) respectively. CONCLUSION: This study aims to
      provide a better understanding of care needs in early dementia. Given population
      aging, the study findings will provide evidence assisting decision-making for
      policies aimed at reducing the burden of caregiving and preserving the QoL of
      dementia patients.

PMID- 21729417
TI  - Sheltered housing or community dwelling: quality of life and ageism among elderly
      people.
AB  - BACKGROUND: Previous studies have found correlations between negative perceptions
      of old age and perceived quality of life (QoL) among elderly people. It has also
      been suggested that a denial of aging mechanism is employed and might support
      ageist attitudes among private-sheltered housing tenants compared with elderly
      people who live in the community and experience intra-generational interactions.
      Therefore, we hypothesized that tenants of sheltered housing will report more
      ageist attitudes towards people of their own age, and report a lower QoL than
      elderly people who live in the community. METHODS: The sample included 126
      volunteers, aged between 64 and 94 years, who live in private-sheltered housing
      (n = 32) or in the community (n = 94). The participants completed the Fraboni
      scale of ageism, and a QoL Inventory (SF-36). RESULTS: People, and men in
      particular, who live in sheltered housing, reported more intergenerational ageist
      attitudes than men and women who live in the community. Tenants in sheltered
      housing expressed lower evaluations of their mental health, but higher
      evaluations on "social functioning" (QoL scales). Women from sheltered housing
      reported better mental health than men. Gender and some QoL scales were
      associated with higher ageism. CONCLUSIONS: Differences in ageist attitudes
      between both dwelling places can be interpreted according to Social Identity
      Theory, which refers to the impact of the ingroup on social attitudes.
      Differences in QoL can be understood by the accessibility of social activities in
      private-sheltered housing. Gender differences in ageism and QoL can be explained
      by women's better social adjustment. Findings should be regarded with caution
      because of the small sample.

PMID- 21729418
TI  - Amyloid imaging.
AB  - Molecular neuroimaging techniques such as PET are proving valuable in the early
      and differential diagnosis of Alzheimer's disease (AD).With the advent of new
      therapeutic strategies aimed at reducing beta-amyloid (Abeta) burden in the brain
      to potentially prevent or delay functional and irreversible cognitive loss, there
      is increased interest in developing agents that allow assessment of Abeta burden
      in vivo. Amyloid imaging with PET has proven useful in the discrimination of
      dementias, showing significantly higher Abeta burden in the gray matter of AD
      patients when compared with healthy controls or patients with frontotemporal
      dementia. ApoE epsilon4 carriers, independent of diagnosis or disease severity,
      present with higher Abeta burden than non-epsilon4 carriers. Amyloid imaging
      matches histopathological reports in aging and dementia, reflecting the true
      regional density of Abeta plaques in cortical areas. It also appears to be more
      sensitive than FDG-PET for the diagnosis of AD. In healthy older people there is
      an increasing prevalence of amyloid positive scans with age, rising from 20% in
      the seventh decade to 60% in the ninth decade. Of people with mild cognitive
      impairment (MCI), 40-60% present with detectable cortical Abeta deposition. In
      both groups, Abeta deposition is associated with a higher risk for cognitive
      decline and dementia due to AD. These observations suggest that Abeta deposition
      is not part of normal aging, supporting the hypothesis that it occurs well before
      the onset of symptoms and is likely to represent preclinical AD in asymptomatic
      persons and prodromal AD in MCI. Further longitudinal observations, coupled with
      different disease-specific tracers and biomarkers, are required to confirm this
      hypothesis and further elucidate the precise role of Abeta deposition in the
      course of AD.

PMID- 21729419
TI  - Structural MRI.
AB  - Clinical neuroimaging is increasingly being used in the diagnosis of
      neurodegenerative diseases and has become one of the most important paraclinical
      tools in the diagnosis of dementia. According to current guidelines,
      neuroimaging, preferably magnetic resonance imaging (MRI), should be performed at
      least once during the diagnostic work-up of patients with suspected or definite
      dementia. MRI is helpful in identifying or excluding potentially treatable causes
      of dementia; however, these account only for a small proportion of dementias. In
      addition, MRI is able to support the clinical diagnosis in a memory clinic
      setting by identifying certain patterns of atrophy and vascular damage. Visual
      rating scales are well-established methods in the clinical routine for the
      assessment and quantification of regional/global cortical atrophy, hippocampal
      atrophy and vascular damage. In addition, MRI is able to detect certain aspects
      of pathology associated with dementia, such as cerebral microbleeds which are
      related to cerebral amyloid angiopathy and Alzheimer pathology. This review paper
      aims to give an overview of the application of structural MRI in the diagnostic
      procedure for memory clinic patients in terms of excluding and supporting the
      diagnosis of various diseases associated with dementia.

PMID- 21729420
TI  - The use of CT in dementia.
AB  - Neuroimaging has become part of the required investigations when assessing a
      patient with dementia. In this brief paper, we summarize the role of computed
      tomography (CT) in the routine work-up in dementia and provide some information
      about the role of the CT scan in the field of dementia research. Although CT is
      far less sensitive than magnetic resonance imaging (MRI) in detecting changes
      associated with cognitive impairment, it may still have a role in this regard.
      This role is mainly that of detecting secondary, sometimes treatable causes of
      cognitive impairment, such as intracranial masses. In this sense, CT should be
      seen as a first-line tool. Possible advantages of CT are lower cost; shorter
      acquisition time, making it more adaptable to patients with poor compliance; and
      the possibility that it can be performed in patients with metal devices, such as
      a pacemaker. The role of CT in the field of dementia research is very restricted
      in comparison to that of MRI, and is limited to the structural assessment of
      vascular lesions, and to a lesser extent, to that of degenerative changes,
      particularly when using specific slicing.

PMID- 21729421
TI  - Perfusion SPECT and FDG-PET.
AB  - Both perfusion SPECT and FDG-PET provide images that closely reflect neuronal
      activity. There is a characteristic regional impairment in Alzheimer's disease
      (AD) that involves mainly the temporo-parietal association cortices, mesial
      temporal structures and to a more variable degree also the frontal association
      cortex. This pattern of functional impairment can provide a biomarker for
      diagnosis of AD and other neurodegenerative dementias at the clinical stage of
      mild cognitive impairment, and for monitoring of progression. FDG-PET is
      quantitatively more accurate and thus better suited to multicenter studies than
      perfusion SPECT. Regional metabolic and blood flow changes are closely related to
      clinical symptoms, and most areas involved in these changes will also develop
      significant cortical atrophy. FDG-PET is complementary to amyloid PET, which
      targets a molecular marker that does not have a close relation to current
      symptoms. Current restrictions in the availability and cost of FDG-PET are being
      reduced, as oncological FDG-PET is being adopted as a standard clinical service
      in most countries. Limitations in the availability of trained staff should be
      overcome by training programs set up by professional organizations. Against the
      background of the development of new criteria for diagnosing AD before the onset
      of dementia, FDG-PET is expected to play an increasing role in diagnosing
      patients at an early stage of AD and in clinical trials of drugs aimed at
      preventing or delaying the onset of dementia.

PMID- 21729422
TI  - Evolution, depression and the interplay between chance and choices.

PMID- 21729423
TI  - Increased serum levels of dehydroepiandrosterone (DHEA) and interleukin-6 (IL-6)
      in women with mild to moderate Alzheimer's disease.
AB  - BACKGROUND: It has been suggested that hypercortisolism contributes to the
      pathophysiology of Alzheimer's disease (AD), based on the fact that excess
      glucocorticoid exposure has potent adverse effects on the central nervous system.
      In contrast, dehydroepiandrosterone (DHEA) has been linked to a broad range of
      beneficial physiological effects including neuronal excitability and
      neuroprotection and even memory enhancing properties. Of note, proinflammatory
      cytokines are present in neuritic plaques (a hallmark of AD) and may regulate
      cortisol/DHEA release. In this exploratory study, we hypothesized that there is a
      flattened diurnal curve of cortisol and DHEA in mild to moderate AD, linked to
      increased cytokine levels. METHODS: Diurnal profiles of cortisol,
      adrenocorticotropic hormone (ACTH), and DHEA were studied in 15 patients with
      mild to moderate AD (7 men and 8 women, 75.6 +/- 5.5 years) and 15 healthy
      elderly controls (7 men and 8 women, 73.3 +/- 5.8 years, respectively).
      Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and soluble TNF
      receptors were analyzed. RESULTS: Women with AD had significantly increased
      morning levels of ACTH, DHEA, and IL-6 compared to healthy elderly women.
      Cortisol levels were significantly increased in men with AD at 0300 h versus
      healthy elderly men, in spite of slightly decreased ACTH levels. CONCLUSIONS: Our
      data suggest important sex differences in hypothalamic-pituitary-adrenal (HPA)
      axis regulation and steroid hormone clearance in patients with AD. Increased
      secretion of IL-6 may have a contributory role in this difference.

PMID- 21729424
TI  - The effects of exposure to scenarios about dementia on stigma and attitudes
      toward dementia care in a Chinese community.
AB  - BACKGROUND: This study investigated whether brief exposure to information has any
      effect on stigmatizing attitudes towards older people with dementia, and how
      people responded to this medical diagnosis. METHODS: 494 adults were randomly
      assigned to three groups differentiated by experimental conditions. Group A
      (control) responded to questions on stigma directly. Group B (symptom) read two
      vignettes that described the symptoms of two fictitious individuals with
      dementia, before answering questions on stigma. Group C (label) read the same
      vignettes which ended with a statement that the person was recently diagnosed
      with dementia by a physician. Data were analyzed with ANOVA, together with other
      pre-existing between-subjects factors. RESULTS: Brief exposure to information
      about dementia led to a statistically significant reduction in stigma (Groups B,
      C < A), regardless of whether the diagnostic label of "dementia" was included or
      not. Moreover, lower stigma was reported by persons who knew a relative or friend
      with dementia, who were younger and more educated, and who thought dementia was
      treatable. CONCLUSIONS: As stigmatizing attitudes toward dementia are still a
      hindrance to early help-seeking in Asian communities, the findings suggest that
      community education may play a useful role in alleviating this barrier to early
      detection and intervention.

PMID- 21729425
TI  - Age- and gender-specific prevalence and risk factors for depressive symptoms in
      the elderly: a population-based study.
AB  - OBJECTIVES: Information on the prevalence and risk factors for depressive
      disorders in old age is of considerable interest for the assessment of future
      needs of the health care system. The aim of the study is to determine age- and
      gender-specific prevalence of major depression (MD), minor depression (MiD), and
      depressive symptoms, and to analyze risk factors associated with depressive
      symptoms. METHODS: A representative sample of the German population of 1,659
      individuals aged 60 to 85 years were visited at home and answered self-rating
      questionnaires. Depressive symptoms and syndromes (MD, MiD) were assessed using
      the Patient Health Questionnaire (PHQ-9). Factors associated with depressive
      symptoms were determined with linear regression models for the total sample and
      for men and women separately. RESULTS: Depressive symptoms were found in 28.7% of
      the participants, while 6.6% were affected by MD or MiD. The highest prevalence
      of MD and depressive symptoms was found in the oldest age groups. MiD showed an
      unsteady course across age groups in both sexes. In the total sample as well as
      in the male subsample, depressive symptoms were significantly associated with
      increasing age, lower household income, an increasing number of medical
      conditions, and lower social support. In women only, the number of medical
      conditions and lacking social support were significantly associated with
      depressive symptoms. CONCLUSIONS: Depressive symptoms are common in old age and
      occur on a spectrum ranging from very mild forms to MD. The potential
      modifiability of a number of risk factors for depressive symptoms opens
      possibilities of secondary prevention such as treatment of chronic diseases as
      well as support in requirements of daily living.

PMID- 21729426
TI  - The use of the Digit Span Test in screening for cognitive impairment in acute
      medical inpatients.
AB  - BACKGROUND: There is no valid instrument currently in use at acute-care hospitals
      in Hong Kong to aid the detection of cognitive impairment. The objectives of this
      study were to (1) validate the Digit Span Test (DST) in the identification and
      differentiation of dementia and delirium; and (2) determine the prevalence of
      major cognitive impairment in elderly people in an acute medical unit. METHODS:
      During the study period from January to February 2010, 144 patients aged 75 years
      or more who had had unplanned medical admissions were assessed by nurses, using
      the Digit Span Forwards (DSF) and the Digit Span Backwards (DSB) tests. The DST
      scores were compared with the psychiatrists' DSM-IV-based diagnoses. Receiver
      Operating Characteristics curve (ROC) was used in conjunction with sensitivity
      and specificity measures to assess the performance of DST. RESULTS: The
      prevalence rates of dementia alone, delirium alone and delirium superimposed on
      dementia were 21.5%, 9% and 9% respectively. The prior case-note documentation
      rate was 13.2% for dementia and 2.8% for delirium. Regarding the detection of
      major cognitive impairment, the ROC curve of DSB showed a sensitivity of 0.77 and
      specificity of 0.78 at the optimal cutoff of <3. A significant association
      between scores on the DST and the Cantonese version of the Mini-Mental State
      Examination (CMMSE) was found in this study (p < 0.05 for DSF, p = 0.00 for DSB).
      CONCLUSIONS: Dementia and delirium were prevalent, yet under-recognized, in acute
      medical geriatric inpatients. The DSB is an effective tool in identifying
      patients with major cognitive impairment.

PMID- 21729427
TI  - Retraction technique in open-approach rhinoplasty.
AB  - BACKGROUND: Various techniques are used to maintain retraction of the skin flap
      during open-approach rhinoplasty. OBJECTIVE: This report aims to present the use
      of maxillofacial retractors in open-approach rhinoplasty, a previously
      undescribed technique. CONCLUSION: Use of these retractors provides excellent
      exposure of the lower lateral cartilages for surgery of the nasal tip, as well as
      access for surgery on the upper lateral cartilages. This technique allows the
      surgeon and assistant to proceed with surgery without needing to maintain
      retraction with a hand-held instrument.

PMID- 21729428
TI  - Correlation between speech-evoked auditory brainstem responses and transient
      evoked otoacoustic emissions.
AB  - OBJECTIVE: To investigate the correlation between cochlear processing and
      brainstem processing. METHOD: Transient evoked otoacoustic emissions and speech
      evoked auditory brainstem responses were recorded in 40 ears of normal-hearing
      individuals aged 18 to 23 years. Correlation analyses compared transient evoked
      otoacoustic emission parameters with speech-evoked auditory brainstem response
      parameters. RESULTS: There was a significant correlation between speech-evoked
      auditory brainstem response wave V latency and transient evoked otoacoustic
      emission global emission strength; there were no other significant correlations
      between the two tests. CONCLUSION: Tests for transient evoked otoacoustic
      emissions and speech-evoked auditory brainstem responses provide unique and
      functionally independent information about the integrity and sensitivity of the
      auditory system. Therefore, combining both tests will provide a more sensitive
      clinical battery with which to identify the location of different disorders (e.g.
      language-based learning impairments and hearing impairments).

PMID- 21729429
TI  - Risk of bleeding after thyroid surgery: matched pairs analysis.
AB  - OBJECTIVE: To identify those patients most at risk of developing a compressive
      post-operative haematoma following thyroid surgery. METHOD: Retrospective
      analysis of patients undergoing thyroid surgery. Factors associated with the
      group of patients who developed a post-operative haematoma were examined using a
      matched pairs, case-control design. RESULTS: Following 355 thyroid operations,
      seven patients developed a post-operative haematoma requiring return to the
      operating theatre for bleeding control. A post-operative systolic blood pressure
      of greater than 150 mmHg, in the post-anaesthetic care unit, was the major
      significant factor identified by regression analysis (p = 0.002). Current smoking
      status was also a significant factor (p = 0.04). CONCLUSION: In our facility, a
      post-anaesthetic systolic blood pressure in excess of 150 mmHg was associated
      with an increased risk of haemorrhage following thyroid surgery.

PMID- 21729430
TI  - Systematic review of vestibular disorders related to human immunodeficiency virus
      and acquired immunodeficiency syndrome.
AB  - INTRODUCTION: Disorders of the auditory and vestibular system are often
      associated with human immunodeficiency virus infection and acquired
      immunodeficiency syndrome. However, the extent and nature of these vestibular
      manifestations are unclear. OBJECTIVE: To systematically review the current peer
      reviewed literature on vestibular manifestations and pathology related to human
      immunodeficiency virus and acquired immunodeficiency syndrome. METHOD: Systematic
      review of peer-reviewed articles related to vestibular findings in individuals
      with human immunodeficiency virus infection and acquired immunodeficiency
      syndrome. Several electronic databases were searched. RESULTS: We identified 442
      records, reduced to 210 after excluding duplicates and reviews. These were
      reviewed for relevance to the scope of the study. DISCUSSION: We identified only
      13 reports investigating vestibular functioning and pathology in individuals
      affected by human immunodeficiency virus and acquired immunodeficiency syndrome.
      This condition can affect both the peripheral and central vestibular system,
      irrespective of age and viral disease stage. Peripheral vestibular involvement
      may affect up to 50 per cent of patients, and central vestibular involvement may
      be even more prevalent. Post-mortem studies suggest direct involvement of the
      entire vestibular system, while opportunistic infections such as oto- and
      neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting
      in vertigo, dizziness and imbalance. CONCLUSION: Patients with human
      immunodeficiency virus and acquired immunodeficiency syndrome should routinely be
      monitored for vestibular involvement, to minimise functional limitations of
      quality of life.

PMID- 21729431
TI  - Audiological manifestations of allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is associated with excess specific immunoglobulin
      E. Inner ear involvement (via both cellular and humoral immunity) is poorly
      understood, but appears to arise from the endolymphatic sac and duct. AIMS: To
      assess the otological and audiological status of patients with allergic rhinitis.
      METHODOLOGY: Thirty allergic rhinitis patients (14 men, 16 women; age 17-45
      years, mean 31 years) and 20 controls (12 men, eight women; age 21-42 years, mean
      27 years) underwent audiological investigation. RESULTS: All study group patients
      had sensorineural (rather than conductive) hearing loss, worse at high
      frequencies. All had abnormal transient evoked otoacoustic emissions and 27 had
      abnormal distortion product otoacoustic emissions. All had a statistically
      significantly prolonged wave I latency, and shortened absolute wave I-III and I-V
      interpeak latencies, compared with controls. CONCLUSION: Allergic rhinitis
      patients had a higher prevalence of hearing loss and otoacoustic emission
      abnormalities than controls. The endolymphatic sac can process antigens and
      produce its own local antibody response; the resulting inflammatory mediators and
      toxic products may interfere with hair cell function. Additional research is
      needed to determine the clinical value of audiometry and otoacoustic emission
      testing in allergic rhinitis.

PMID- 21729432
TI  - Large, solitary angiokeratoma in the posterior third and base of the tongue: case
      report.
AB  - OBJECTIVE: We present an extremely rare case of isolated angiokeratoma of the
      tongue. METHOD: Case report and review of related literature. RESULTS: An 18-year
      old, male adolescent presented with a fleshy, intermittently bleeding mass in the
      posterior third and base of the tongue. The lesion was initially suspected to be
      a lingual thyroid or haemangioma, but histopathological features were consistent
      with angiokeratoma. Magnetic resonance imaging revealed that the lesion extended
      up to the vallecula and involved the lamina propria and superficial tongue
      musculature. No similar lesions were found elsewhere in the body. No metabolic
      derangements were identified in the patient or his family. The 2.6 * 1.5 * 0.5 cm
      mass was excised under general anaesthesia. CONCLUSION: We present the 1st case
      of isolated lingual angiokeratoma in a male, the 4th such case overally, the
      largest ever documented. The lesion was situated in the posterior third and base
      of the tongue, a position not previously described.

PMID- 21729433
TI  - Effect of early postnatal air-conduction auditory deprivation on the development
      and function of the rat spiral ganglion.
AB  - OBJECTIVE: To evaluate the effect of early postnatal air-conduction auditory
      deprivation on the development and function of the rat spiral ganglion. STUDY
      DESIGN: Randomised animal study. METHODS: Sixty neonatal Sprague-Dawley rats were
      randomly divided into two groups: controls (n = 30) given regular chow and water
      ad libitum; and study animals (n = 30) fed within a soundproof chamber. Auditory
      brainstem response testing was conducted in both groups on postnatal day 42.
      RESULTS: Auditory deprivation between postnatal days 12 and 42 resulted in an
      increased hearing threshold and reduced auditory brainstem response amplitudes,
      together with degeneration of type I spiral ganglion neurons and the presence of
      apoptotic cells. CONCLUSION: Non-invasive auditory deprivation during a critical
      developmental period resulted in numerous changes in rat cochlear function and
      morphology.

PMID- 21729434
TI  - Influence of tinnitus sound therapy signals on the intelligibility of speech.
AB  - OBJECTIVE: To assess the influence on speech intelligibility of various signals
      used in tinnitus sound therapy. MATERIALS AND METHODS: We measured, in normal
      hearing subjects, the intelligibility of speech in the presence of three
      different sound therapy signals: wide-band noise, a recording of moving water,
      and a combination of tones. RESULTS: For a given level of stimulation, speech
      intelligibility was worst in the presence of wide-band noise, compared with the
      other sound therapy signals. When the stimulation level of the three different
      signals was increased, speech intelligibility deteriorated more rapidly with wide
      band noise, compared with the other two signals. The combination of tones had the
      least influence on speech intelligibility. CONCLUSION: The use of different
      tinnitus sound therapy signals can lead to significantly different effects on the
      intelligibility of speech. The use of natural sound recordings or combinations of
      tones may provide the patient with more flexibility to change the stimulation
      level during treatment.

PMID- 21729435
TI  - Audit of handover in an ENT unit.
AB  - OBJECTIVES: To analyse the completeness and accuracy of the written handover in
      our ENT department, in line with Royal College of Surgeons of England guidance,
      and to improve standards. SETTING: University Hospital, Cumberland Infirmary,
      Carlisle, UK. METHODS AND RESULTS: We prospectively analysed the written handover
      over two periods (of 30 and 18 days each). In the first period, the morning
      handover was present and complete on 77 per cent of days, present but incomplete
      or illegible on 6 per cent of days, and absent on 17 per cent of days; the
      evening handover was present and complete on 30 per cent of days, and absent on
      67 per cent of days. To improve standards, we emphasised the importance of
      accurate handover to the ENT team and to junior doctors who cross-covered ENT. A
      reminder of the Royal College of Surgeons of England guidance was included in the
      handover book, and junior doctors received regular feedback. CONCLUSION: We
      demonstrated a substantial improvement in the quality and completeness of written
      handover, comparing the second and first audit periods.

PMID- 21729436
TI  - External frontal sinusotomy and endoscopic repair of cerebrospinal fluid fistula
      in the posterior wall: preliminary report of a new technique.
AB  - INTRODUCTION: Cerebrospinal fluid rhinorrhoea is the abnormal leakage of
      cerebrospinal fluid into the nasal cavity. The posterior wall of the frontal
      sinus can be the site of such leakage. Traditionally, these leaks were repaired
      via external osteoplastic or neurosurgical approaches. Despite advances in
      instrumentation, it is difficult to manage superiorly or laterally placed defects
      endoscopically. We present a new technique of endoscopic repair of frontal sinus
      posterior wall defects, via access holes drilled in the anterior wall of the
      frontal sinus. STUDY DESIGN: Preliminary study involving patients presenting with
      frontal sinus cerebrospinal fluid leaks, with defects in the frontal sinus
      posterior wall, between 2006 and 2010. SETTING: Patients were treated in a
      tertiary referral centre for nose and sinus diseases. Patient records were
      reviewed and analysed. RESULTS: Nine patients underwent external frontal
      sinusotomy under endoscopic vision. Repair was successful in all cases, with no
      complications. Follow up ranged from three months to three years. CONCLUSION:
      External frontal sinusotomy and endoscopic repair is a simple, precise and
      cosmetically acceptable alternative to osteoplastic and major neurosurgical
      techniques for management of frontal sinus posterior wall defects. This new,
      previously undescribed technique enables otolaryngologists to play a role in
      managing such defects.

PMID- 21729437
TI  - High frequency hearing loss in the elderly: effect of age and noise exposure in
      an Italian group.
AB  - OBJECTIVE: To describe the effect of age and noise on high frequency hearing
      thresholds in an Italian population aged 70 years and older, in order to
      investigate the interaction between presbycusis and noise exposure. METHODS: We
      compared 460 subjects: 367 affected by presbycusis alone (204 women and 163 men)
      and 93 affected by presbycusis and noise exposure (eight women and 85 men). Pure
      tone average hearing thresholds, for each ear, were compared between groups, and
      between sexes and ages within groups. RESULTS: A slight threshold difference was
      found between the two groups at 4 kHz. After adjusting for age and gender, this
      difference was found to be related only to differing patient age. Men's and
      women's thresholds differed significantly in both groups, especially at high
      frequencies, at which threshold deterioration was worse in men than women.
      CONCLUSION: The threshold differences between patients with presbycusis with and
      without noise exposure were limited. Larger studies are needed to assess the
      relative effects of ageing and noise exposure on hearing thresholds.

PMID- 21729438
TI  - Pyriform sinus haemangioma: an unusual presentation of an unusual condition.
AB  - OBJECTIVE: We present a rare case of an unusual presentation of a pyriform sinus
      haemangioma in a normally healthy, Caucasian woman, including our management and
      a review of the literature. CASE REPORT: A 44-year-old woman presented
      complaining of bringing up fresh blood whilst brushing her teeth, dysphonia, food
      sticking in her throat, and epigastric pain for the preceding 12 months,
      accompanied by a 17.5 kg weight loss. She underwent pre-operative computed
      tomography and subsequent complete excision of a pyriform sinus haemangioma using
      CO2 laser. DISCUSSION: Haemangiomas are congenital vascular malformations and can
      affect any part of the body. They are not prevalent in adults and are rarely
      found in the pyriform sinus. Their common presenting symptoms and management have
      been previously documented; however, the presented case is unusual in both its
      presentation and management.

PMID- 21729439
TI  - Dislocation of the inferior turbinates: a rare complication of nasal surgery,
      presenting as obstructive sleep apnoea.
AB  - OBJECTIVE: We report a very rare complication of nasal surgery: dislocation of
      the inferior turbinates into the nasopharynx, presenting as sleep apnoea and
      persistent nasal obstruction. CASE REPORT: A 56-year-old woman presented with a
      history of obstructive sleep apnoea for one year and nasal obstruction for seven
      years. She had undergone nasal surgery one year previously. Non-contrast computed
      tomography of the nose and paranasal sinuses showed a mass near the posterior
      choana on both sides, confirmed by nasal endoscopy. The displaced turbinates were
      removed, after resecting their attachment at the posterior choanae, and the
      patient's symptoms were relieved. CONCLUSION: This is a very rare complication of
      nasal surgery; to the best of our knowledge, we report only the second published
      case in the English language literature. We suggest that such cases be closely
      followed up post-operatively.

PMID- 21729440
TI  - Endoscopic management of rhinocerebral mucormycosis with topical and intravenous
      amphotericin B.
AB  - OBJECTIVE: Mucormycosis is an aggressive fungal infection which may still cause
      fatal complications. However, the rarity of this disease has made optimal
      treatment a controversial issue. This study aimed to evaluate the use of topical
      amphotericin B in endoscopic management of rhinocerebral mucormycosis. SUBJECTS
      AND METHODS: Thirty patients with infection limited to the nose and sinuses were
      selected. Patients underwent endoscopic debridement of all necrotic tissue;
      cottonoid pledgets soaked in amphotericin B solution were then placed in the
      nasal cavity. Subsequently, long-term antifungal therapy was administered.
      RESULTS: The overall survival rate was 60 per cent (18 cases); survival rates in
      the diabetic and malignancy groups were 70.58 and 40 per cent, respectively.
      Apart from predisposing factors, orbital and maxillary sinus involvement also had
      a significant correlation with patient outcome. CONCLUSION: Topical use of
      amphotericin B combined with endoscopic surgical debridement, followed by
      intravenous amphotericin B treatment, may constitute acceptable management for
      selected patients, with less morbidity than conventional treatments.

PMID- 21729441
TI  - Leiomyosarcoma of the tonsil.
AB  - OBJECTIVE: We report a case of leiomyosarcoma arising in the tonsil in a 73-year
      old man. METHOD: Case report and review of the English language literature (using
      Pubmed, Ovid and Proquest databases). RESULTS: To our knowledge, this is the
      first case of tonsillar leiomyosarcoma to be reported in the English language
      literature. Our patient presented with haemoptysis, unilateral odynophagia and an
      ulcerated, exophytic lesion of the tonsil. Histological examination confirmed the
      diagnosis of leiomyosarcoma, and the patient was treated with radical
      radiotherapy. CONCLUSION: Leiomyosarcomas are extremely rare in the head and
      neck; the common sites of origin are the skin and sinonasal tract. The overall
      prognosis is poor.

PMID- 21729442
TI  - Coblation-assisted endonasal endoscopic resection of juvenile nasopharyngeal
      angiofibroma.
AB  - OBJECTIVE: Juvenile nasopharyngeal angiofibroma may be successfully resected
      using endoscopic techniques. However, the use of coblation technology for such
      resection has not been described. This study aimed to document cases of Fisch
      class I juvenile nasopharyngeal angiofibroma with limited nasopharyngeal and
      nasal cavity extension, which were completely resected using an endoscopic
      coblation technique. METHODS: We retrospectively studied 23 patients with
      juvenile nasopharyngeal angiofibroma who underwent resection with either
      traditional endoscopic instruments (n = 12) or coblation (n = 11). Intra
      operative blood loss and overall operative time were recorded. RESULTS: The mean
      tumour resection time for coblation and traditional endoscopic instruments was 87
      and 136 minutes, respectively (t = 9.962, p < 0.001). Mean intra-operative blood
      loss was 121 and 420 ml, respectively (t = 28.944, p < 0.001), a significant
      difference. Both techniques achieved complete tumour resection with minimal
      damage to adjacent tissues, and no recurrence in any patient. CONCLUSION:
      Coblation successfully achieves transnasal endoscopic resection of juvenile
      nasopharyngeal angiofibroma (Fisch class I), with good surgical margins and
      minimal blood loss.

PMID- 21729443
TI  - Effect of primary, cross-over, zigzag neopharyngoplasty on acoustic
      characteristics of alaryngeal, tracheoesophageal voice.
AB  - OBJECTIVE: To evaluate the effect of primary, cross-over, zigzag neopharyngeal
      construction on tracheoesophageal voice, compared with pharyngoesophageal
      myotomy, following total laryngectomy with partial pharyngectomy. STUDY DESIGN:
      Prospective clinical trial. SETTING: Otolaryngology department, Tanta University
      Hospital (tertiary referral centre), Egypt. PATIENTS AND METHODS: Over five
      years, 30 patients underwent total laryngectomy with partial pharyngectomy to
      manage stage III or IV laryngeal cancer, followed by primary tracheoesophageal
      puncture for voice restoration. For neopharyngeal construction, 15 patients
      underwent pharyngoesophageal myotomy (group one) and 15 cross-over, zigzag
      neopharyngoplasty (group two). Acoustic parameters of tracheoesophageal voice
      were compared. RESULTS: Most acoustic parameters were almost equivalent for the
      two groups, although significant differences were seen for loud intensity,
      dynamic range, shimmer, loud fundamental frequency, loud jitter, fluency and
      speaking rate. One post-operative pharyngocutaneous fistula (6.6 per cent)
      occurred in each group, and resolved with conservative measures. CONCLUSION: The
      cross-over neopharyngoplasty modification of hypopharyngeal closure may help
      avoid pharyngoesophageal spasm and assist maintenance of effective voice
      amplitude, fundamental frequencies, temporal measures and perceptual values.

PMID- 21729444
TI  - In vitro induction and differentiation of newborn guinea pig hippocampus neural
      stem cells into cells resembling inner hair cells, using artificial perilymph.
AB  - OBJECTIVE: To investigate whether artificial perilymph can induce neural stem
      cells, derived from the hippocampus of newborn guinea pigs, to differentiate into
      inner ear hair cells, in vitro. METHODS: Primary neural stem cells derived from
      the hippocampus of newborn guinea pigs were incubated in medium containing either
      10 per cent fetal bovine serum or 5, 10 or 15 per cent artificial perilymph, for
      three weeks. Differentiated cells were identified using immunofluorescence,
      Western blot and scanning electron microscopy. RESULTS: Both fetal bovine serum
      and artificial perilymph induced the neural stem cells to differentiate into
      cells with hair-cell-specific antibodies. CONCLUSION: Neural stem cells can
      survive in both fetal bovine serum and artificial perilymph, and within these
      media can differentiate into cells with hair-cell-specific antibodies. This
      provides an experimental basis for transplantation of neural stem cells into the
      inner ear.

PMID- 21729445
TI  - Tracheal resection with end-to-end anastomosis for post-intubation cervical
      tracheal stenosis: study of 14 cases.
AB  - BACKGROUND AND OBJECTIVES: The incidence of acquired laryngeal stenosis is
      increasing. This retrospective study aimed to assess the long term results of
      circumferential resection with end-to-end tracheal anastomosis for isolated post
      intubation stenosis of the cervical trachea, and to review the relevant
      literature. METHODS: Twelve male and two female patients (aged 16-30 years, mean
      age 24 years) treated between February 2003 and December 2008 were included.
      Hospital and office records were reviewed and relevant surgical details recorded.
      RESULTS: Indications for tracheal resection anastomosis were post-intubation
      stenosis (78.57 per cent) and trauma (21.42 per cent). One to five tracheal rings
      were resected (i.e. 1-2.5 cm of cervical trachea). Tracheal anastomosis was
      considered successful if the patient remained asymptomatic for 24 months of close
      follow up (involving regular flexible bronchoscopy and neck X-ray). The
      anastomotic success rate was 92.85 per cent. CONCLUSION: Tracheal resection and
      end-to-end anastomosis is relatively safe and reliable for definitive treatment
      of benign tracheal stenosis in appropriate patients. Local application of
      mitomycin C prevents granulation and aids long term airway patency.

PMID- 21729446
TI  - A Hunsaker Mon-Jet tube trapped in the larynx.
AB  - OBJECTIVE: We report a unique complication arising from the use of a Hunsaker Mon
      Jet ventilation tube during microlaryngeal surgery, and we briefly review the
      literature on the use of this tube for jet ventilation. METHOD: A case report on
      the safe and successful management of a potential airway compromise, and a brief
      literature review on using the Hunsaker Mon-Jet ventilation tube during
      microlaryngeal surgery. CASE REPORT: A 46-year-old woman was scheduled to undergo
      removal of a vocal cord polyp under general anaesthesia. However, the polyp
      became stuck in the basket of the Hunsaker tube during intubation. The polyp and
      the Hunsaker tube were removed safely after a microlaryngeal tube was passed
      beyond the vocal cords. To our knowledge, this complication has not previously
      been reported. CONCLUSION: This case highlights the potential risk of laryngeal
      growths, especially vocal cord polyps, becoming trapped in the Hunsaker tube
      during intubation. Both the anaesthetist and the operating surgeon should be
      aware of this possible complication and, more importantly, how to deal with such
      a problem.

PMID- 21729447
TI  - Is it oncologically safe to leave the ipsilateral submandibular gland during neck
      dissection for head and neck squamous cell carcinoma?
AB  - AIM: To investigate the incidence of metastasis to the submandibular gland in
      patients with head and neck squamous cell carcinoma. METHODS: We retrospectively
      evaluated histological reports of neck dissections for upper respiratory tract
      carcinoma (performed 2002-2009), recording: primary tumour site, tumour-node
      metastasis stage, level Ib involvement, previous radiotherapy, perineural
      invasion, lymphovascular invasion, extracapsular spread, and the presence of
      malignant disease in the submandibular gland. RESULTS: We evaluated 107 cases.
      The most common primary site was the oral cavity (49 per cent) followed by the
      supraglottis (21 per cent), glottis (14 per cent), oropharynx (9 per cent) and
      hypopharynx (6 per cent). Forty-eight per cent of patients had advanced local
      disease, with 21 per cent at tumour stage 3 and 27 per cent at tumour stage 4.
      Fifty-six per cent had cervical lymph node metastasis, and 8 per cent received
      pre-operative radiotherapy. Forty-eight per cent had perineural invasion, 46 per
      cent lymphovascular spread, 27 per cent extracapsular spread and 8 per cent level
      Ib metastasis. Only one patient had submandibular gland involvement, due to
      direct spread (a case with prior radiotherapy and macroscopic submandibular gland
      involvement evident peri-operatively). CONCLUSION: Submandibular gland metastasis
      from head and neck primary squamous cell carcinoma is extremely rare.
      Preservation of the ipsilateral submandibular gland during neck dissection is
      oncologically safe, except in patients with prior surgery or radiotherapy, or a
      primary tumour in close relation to the gland.

PMID- 21729448
TI  - Nasogastric tube insertion in difficult cases with the aid of a flexible
      nasendoscope.
AB  - OBJECTIVE: Nasogastric tube insertion is often difficult, due to a variety of
      reasons, e.g. skewed laryngeal anatomy. We present a previously unreported method
      of facilitating nasogastric tube insertion, using a flexible nasendoscope.
      METHOD: The nasogastric tube is anchored to a flexible nasendoscope using sodium
      alginate dressing ties. The nasendoscope is then passed into the upper
      oesophagus, along with the nasogastric tube. Once the nasogastric tube has passed
      the cricopharyngeus, gentle traction on the nasendoscope releases it from the
      nasogastric tube. The nasendoscope can then be withdrawn. A previous safety study
      of sodium alginate ingestion showed no adverse effects. CONCLUSION: This method
      enables nasogastric tube insertion under direct vision, and allows the tube to be
      guided past the larynx and into the upper oesophagus.

PMID- 21729449
TI  - Tympanoplasty graft preparation using ear drops containing polyethylene glycol,
      flumethasone and clioquinol.
AB  - The aim of tympanoplasty graft preparation is to stiffen the fascia or
      perichondrium and thereby to optimise ease of manipulation. We report 39 cases
      utilising a novel technique in which the graft is prepared in ear drops
      containing polyethylene glycol, flumetasone pivalate (0.02 per cent) and
      clioquinol (1 per cent). This technique is useful in reducing the risk of
      desiccation if placement is delayed, and may pose less risk of infection and
      mechanical damage than alternative methods.

PMID- 21729450
TI  - Assessment of cervical lymph node metastases using indirect computed tomography
      lymphography with iopamidol in a tongue VX2 carcinoma model.
AB  - OBJECTIVE: To investigate the performance of indirect computed tomography
      lymphography with iopamidol for detecting cervical lymph node metastases in a
      tongue VX2 carcinoma model. MATERIALS AND METHODS: A metastatic cervical lymph
      node model was created by implanting VX2 carcinoma suspension into the tongue
      submucosa of 21 rabbits. Computed tomography images were obtained 1, 3, 5, 10, 15
      and 20 minutes after iopamidol injection, on days 11, 14, 21 (six rabbits each)
      and 28 (three rabbits) after carcinoma transplantation. Computed tomography
      lymphography was performed, and lymph node filling defects and enhancement
      characteristics evaluated. RESULTS: Indirect computed tomography lymphography
      revealed bilateral enhancement of cervical lymph nodes in all animals, except for
      one animal imaged on day 28. There was significantly slower evacuation of
      contrast in metastatic than non-metastatic nodes. A total of 41 enhanced lymph
      nodes displayed an oval or round shape, or local filling defects. One lymph node
      with an oval shape was metastatic (one of 11, 9.1 per cent), while 21 nodes with
      filling defects were metastatic (21/30, 70 per cent). The sensitivity,
      specificity, accuracy, and positive and negative predictive values when using a
      filling defect diameter of 1.5 mm as a diagnostic criterion were 86.4, 78.9,
      82.9, 82.6 and 83.3 per cent, respectively. CONCLUSION: When using indirect
      computed tomography lymphography to detect metastatic lymph nodes, filling
      defects and slow evacuation of contrast agent are important diagnostic features.

PMID- 21729451
TI  - Ewing's sarcoma of the masseter muscle.
AB  - OBJECTIVE: To present a case of extraskeletal Ewing's sarcoma originating in the
      masseter muscle, and to review the diagnosis and management of these rare
      tumours. METHODS: Case report and literature review. RESULTS: We report a patient
      with Ewing's sarcoma of the masseter muscle with mandibular invasion. She was
      treated with induction chemotherapy, salvage surgery and free flap
      reconstruction. CONCLUSION: This case highlights the management of these rare
      tumours. Aggressive multi-modal treatment, including multi-agent chemotherapy,
      surgical resection and irradiation, appears to offer the best prognosis.
      Contemporary reconstructive techniques can restore function and form in cases
      with challenging defects.

PMID- 21729452
TI  - Giant fibrovascular polyp of the hypopharynx: per-oral endoscopic removal.
AB  - OBJECTIVE: We report an extremely rare case of giant fibrovascular polyp of the
      hypopharynx. METHOD: We present a 49-year-old man who had increasing difficulty
      swallowing, advanced respiratory distress and weight loss, as well as a
      hypopharyngeal mass protruding from his mouth. RESULTS: Diagnosis was confirmed
      by endoscopic examination and computed tomography. A tracheostomy was required
      due to laryngeal obstruction by the regurgitated mass. The giant polyp was
      removed via per-oral endoscopic excision under general anaesthesia. CONCLUSION:
      Fibrovascular polyps occur most commonly in the cervical oesophagus, and are
      extremely rare in the hypopharynx. They can grow to a very large size over
      several years. We discuss the symptoms, diagnosis and surgical treatment
      techniques for upper aerodigestive tract fibrovascular polyps, in the light of
      the literature.

PMID- 21729453
TI  - Solitary extra-skeletal sinonasal metastasis from a primary skeletal Ewing's
      sarcoma.
AB  - INTRODUCTION: Ewing's sarcoma is a rare, malignant tumour predominantly affecting
      young adolescent males. We describe a unique case of an isolated extra-skeletal
      metastasis from a skeletal Ewing's sarcoma primary, arising in the right
      sinonasal cavity of a young man who presented with severe epistaxis and
      periorbital cellulitis. RESULTS: Histologically, the lesion comprised closely
      packed, slightly diffuse, atypical cells with round, hyperchromatic nuclei, scant
      cytoplasm and occasional mitotic figures, arranged in a sheet-like pattern.
      Immunohistochemical analysis showed positive staining only for cluster of
      differentiation 99 glycoprotein. Fluorescent in situ hybridisation identified the
      Ewing's sarcoma gene, confirming the diagnosis. MANAGEMENT: Complete surgical
      resection was achieved via a minimally invasive endoscopic transnasal approach;
      post-operative radiotherapy. Ten months post-operatively, there were no
      endoscopic or radiological signs of disease. CONCLUSION: Metastatic Ewing's
      sarcoma within the head and neck is incredibly rare and can pose significant
      diagnostic and therapeutic challenges. An awareness of different clinical
      presentations and distinct histopathological features is important to enable
      early diagnosis. This case illustrates one potential management strategy, and
      reinforces the evolving role of endoscopic transnasal approaches in managing
      sinonasal cavity and anterior skull base tumours.

PMID- 21729454
TI  - Structural changes and immunohistochemical localisation of epidermal growth
      factor receptor in the true vocal fold of female albino rats administered
      anabolic, androgenic steroids, and effects of anti-androgen therapy.
AB  - BACKGROUND: Anabolic steroid abuse by women is associated with a number of
      adverse effects, including laryngeal changes. The epidermal growth factor
      receptor is related to regulation of the cell life cycle. This study aimed to
      investigate the structural changes and immunohistochemical localisation of
      epidermal growth factor receptor in rat vocal folds following anabolic steroid
      administration, and also to assess the effect of anti-androgens. MATERIAL AND
      METHODS: Thirty-two adult female albino rats were divided into: group I
      (controls), group II (receiving anabolic steroids for two months) or group III
      (receiving anabolic steroids plus anti-androgen for two months). RESULTS: Group
      II rat true vocal folds showed thicker epithelial layers with many mitotic
      figures, thicker lamina propria and thicker muscle fibres; epithelial cells were
      also immunohistochemically positive for epidermal growth factor receptor. Group
      III rats showed similar changes, but thin muscle fibres and extravasated red
      blood cells within the lamina propria. CONCLUSION: Anabolic steroids caused
      structural and immunohistochemical changes within the female rat true vocal fold.
      Co-administration of anti-androgens did not prevent these changes, suggesting
      that anti-androgens have a limited role in the management of such changes in
      humans.

PMID- 21729455
TI  - Rhinocerebral mucormycosis: experience in 14 patients.
AB  - OBJECTIVE: Mucormycosis is an opportunist, often lethal fungal infection which
      occurs in immunocompromised patients. We present our experience in 14 patients
      with this condition. PATIENTS AND METHODS: A retrospective chart review was
      conducted for 14 patients treated for rhinocerebral mucormycosis. RESULTS: Nine
      patients had diabetes mellitus and six had a haematological malignancy. Nine
      patients had cutaneous and/or palatal necrosis. Eleven patients were treated with
      amphotericin B and five with liposomal amphotericin B. Endoscopic sinus surgery
      was performed in five patients with disease limited to the sinonasal cavity; nine
      patients underwent more extensive surgery. Five patients with disease limited to
      the sinonasal cavity survived, while nine patients with widely disseminated
      disease died. Five of the nine diabetic patients died, as did five of the six
      patients with haematological malignancy. CONCLUSION: Patients with rhinocerebral
      mucormycosis spreading outside the sinonasal cavity have a poor prognosis.

PMID- 21729456
TI  - Significance of advanced haemostasis investigation in recurrent, severe post
      tonsillectomy bleeding.
AB  - OBJECTIVE: To evaluate the significance of advanced post-operative haemostasis
      investigation in cases of recurrent, severe post-tonsillectomy bleeding.
      MATERIALS AND METHODS: Of the 120 patients treated at our tertiary centre between
      2006 and 2010 due to post-tonsillectomy haemorrhage, 22 with recurrent, severe
      episodes of bleeding underwent further, advanced haemostasis investigation.
      RESULTS: Underlying haemorrhagic disease was not diagnosed in any case. Isolated
      abnormal clotting factor levels were identified in two patients. Decreased
      fibrinogen concentration due to dilutional coagulopathy was found in nine cases
      (40.9 per cent). CONCLUSION: Recurrent, severe post-tonsillectomy haemorrhage is
      rarely related to undiagnosed haemostatic disorders. Thus, advanced haemostasis
      studies have little therapeutic relevance. However, repetitive post-tonsillectomy
      bleeding may be related to decreased fibrinogen levels due to dilutional
      coagulopathy. Therefore, fibrinogen concentration should be tested, and
      dilutional coagulopathy treated promptly.

PMID- 21729457
TI  - Thyroid cancer: is ethnicity relevant?
AB  - OBJECTIVE: This study aimed to determine the age at which various ethnic groups
      present with thyroid cancer. METHOD: Retrospective, observational study based at
      three district general hospitals in the West Midlands, serving a widely diverse
      ethnic population. We assessed all patients undergoing an operative or core
      biopsy procedure for a thyroid nodule from 1 January 1998 to 31 December 2009.
      Only patients diagnosed with thyroid cancer were included. Variables examined
      included the patient's ethnic origin, sex and age at presentation. RESULT: We
      identified 263 patients diagnosed with thyroid cancer. Papillary carcinoma
      predominated. Ethnicity was categorised as Caucasian, Asian, black or other.
      Thyroid cancer was predominantly seen in women, in all ethnic groups. The mean
      age of thyroid cancer presentation was 50 years in Asians and 56 years in
      Caucasians, for both sexes combined. The mean presentation age of Asian women was
      significantly younger (46 years) than that of Caucasian women (56 years) (p =
      0.01). CONCLUSION: In this population, Asian women presented with thyroid cancer
      at a significantly younger mean age than Caucasian women.

PMID- 21729458
TI  - Food and beverage choices contributing to dietary guidelines adherence in the
      Lower Mississippi Delta.
AB  - OBJECTIVES: The objectives of the present study were to evaluate diet quality
      among Lower Mississippi Delta (LMD) residents using the Healthy Eating Index-2005
      (HEI-2005) and to identify the top five dietary sources contributing to HEI-2005
      components. Demographic differences in HEI-2005 scores were also explored.
      DESIGN: Diet quality was evaluated using HEI-2005. Demographic differences in HEI
      2005 scores were investigated using multivariable regression models adjusting for
      multiple comparisons. The top five dietary sources contributing to HEI-2005
      components were identified by estimating and ranking mean MyPyramid equivalents
      overall and by demographic characteristics. SETTING: Dietary data, based on a
      single 24 h recall, from the Foods of Our Delta Study 2000 (FOODS 2000) were used
      in the analyses. SUBJECTS: FOODS 2000 adult participants 18 years of age or
      older. RESULTS: Younger age was the largest determinant of low diet quality in
      the LMD with HEI-2005 total and seven component scores declining with decreasing
      age. Income was not a significant factor for HEI-2005 total or component scores.
      The top five dietary sources differed by all five of the demographic variables,
      particularly for total vegetables and energy from solid fats, alcoholic beverages
      and added sugars (SoFAAS). Soft drinks were the leading source of SoFAAS energy
      intake for all demographic groups. CONCLUSIONS: The assessment of diet quality
      and identification of top dietary sources revealed the presence of demographic
      differences for selected HEI-2005 components. These findings allow identification
      of food patterns and culturally appropriate messaging and highlight the
      difficulties of treating this region as a homogeneous population.

PMID- 21729459
TI  - Effectiveness of a Canteen Take Away concept in promoting healthy eating patterns
      among employees.
AB  - OBJECTIVE: To investigate the effectiveness of a relatively novel concept of
      providing employees with healthy ready-to-heat meals to bring home to their
      families, here referred to as Canteen Take Away (CTA). DESIGN: Employees' dietary
      intake on two weekdays when they received free CTA was compared with that on
      weekdays when they did not receive CTA. Four non-consecutive 24 h dietary recalls
      were applied to assess dietary intake on a daily basis. Moreover, a digital
      photographic method was used to assess evening meal intake for three consecutive
      weeks. Data were analysed using a mixed-effects model. SETTING: A financial
      worksite offering CTA. SUBJECTS: Twenty-seven employees. RESULTS: Overall dietary
      quality as expressed by the energy density of the food (excluding beverages) was
      found to be significantly lower on days consuming CTA meals compared to days not
      consuming CTA with regard to evening meal intake (average difference: -187 (95 %
      CI -225, -149) kJ/100 g) and on a daily basis (average difference: -77 (95 % CI 
      132, -21) kJ/100 g). Other favourable differences included increased vegetable
      intake (average difference: 83 (95 % CI 67, 98) g/evening meal, 109 (95 % CI 62,
      155) g/d). CONCLUSION: The present study shows that providing healthy take-away
      dinners has potential for promoting healthy dietary habits among employees. This
      reinforces the importance of availability and convenience as effective tools to
      promote healthy eating habits.

PMID- 21729460
TI  - Reducing the population's sodium intake: the UK Food Standards Agency's salt
      reduction programme.
AB  - OBJECTIVE: To describe the UK Food Standards Agency's (FSA) salt reduction
      programme undertaken between 2003 and 2010 and to discuss its effectiveness.
      DESIGN: Relevant scientific papers, campaign materials and evaluations and
      consultation responses to the FSA's salt reduction programme were used. SETTING:
      Adult salt intakes, monitored using urinary Na data collected from UK-wide
      surveys, indicate a statistically significant reduction in the population's
      average salt intake from 9.5 g/d in 2000-2001 to 8.6 g/d in 2008, which is likely
      to have health benefits. SUBJECTS: Reducing salt intake will have an impact on
      blood pressure; an estimated 6 % of deaths from CHD in the UK can be avoided if
      the number of people with high blood pressure is reduced by 50 %. RESULTS: Salt
      levels in food, monitored using commercial label data and information collected
      through an industry self-reporting framework, indicated that substantial
      reductions of up to 70 % in some foods had been achieved. The FSA's consumer
      campaign evaluation showed increased awareness of the benefits of reducing salt
      intake on health, with 43 % of adults in 2009 claiming to have made a special
      effort to reduce salt in their diet compared with 34 % of adults in 2004, before
      the campaign commenced. CONCLUSIONS: The UK's salt reduction programme
      successfully reduced the average salt intake of the population and increased
      consumers' awareness. Significant challenges remain in achieving the population
      average salt intake of 6 g/d recommended by the UK's Scientific Advisory
      Committee on Nutrition. However, the UK has demonstrated the success of its
      programme and this approach is now being implemented elsewhere in the world.

PMID- 21729461
TI  - Dietary patterns and breast-feeding in Australian children.
AB  - OBJECTIVE: To determine the dietary patterns of a national sample of 2-8-year-old
      Australian children and to establish whether breast-feeding is associated with
      dietary patterns in this age group. DESIGN: Cross-sectional study using 24 h
      recall data from the 2007 Australian National Children's Nutrition and Physical
      Activity Survey. SETTING: Australia. SUBJECTS: A total of 2287 children aged 2-8
      years. RESULTS: Principal component factor analysis identified three distinct
      patterns. The 'Non-core food groups' pattern included food groups such as whole
      fat dairy products, cheese, medium-high sugar-sweetened breakfast cereals and
      sweet biscuits, no fruit, reduced/low-fat dairy products and wholegrain
      bread/rolls. The 'Healthy, meat and vegetable' pattern included vegetables, red
      meat, fruit and wholegrain bread/rolls and was inversely associated with take
      away foods and carbonated sugar-sweetened beverages. The 'Combination' pattern
      contained many food groups including candy (not chocolate based), pasta/rice
      products, nuts/seeds, cakes and chocolate, but no fruit or vegetables. Of the
      2287 children, 2064 (89.3 %) had been breast-fed. A positive association was
      found between breast-feeding and the healthy, meat and vegetable pattern (r =
      0.267) but not with the other two patterns. Higher scores on this pattern were
      also associated with younger age, lower BMI, higher birth weight, high likelihood
      of being in the less-disadvantaged Socio-economic Indexes for Areas category and
      less likelihood of the child's parents having a lower educational level.
      CONCLUSIONS: These results provide suggestive evidence that breast-feeding during
      infancy is associated with a healthy dietary pattern in childhood and offers a
      likely pathway to explain the previously reported association between breast
      feeding and chronic disease.

PMID- 21729462
TI  - The impact of prenatal vitamin A and zinc supplementation on growth of children
      up to 2 years of age in rural Java, Indonesia.
AB  - OBJECTIVE: To determine whether prenatal vitamin A and/or Zn supplementation
      affects postnatal growth. DESIGN: Follow-up of a randomized controlled trial
      monitoring growth in children from birth up to 24 months of age. SETTING: Central
      Java, Indonesia. SUBJECTS: Children (n 343) of mothers participating in a double
      blinded, randomized controlled study of vitamin A and/or Zn supplementation
      during pregnancy. We report the effects of prenatal supplementation on infant
      growth, measured as weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ)
      and weight-for-height Z-scores (WHZ ), from 0 to 24 months, as well as
      differences in growth faltering among the supplementation groups. RESULTS: For
      HAZ, the absolute differences between the vitamin A-only and vitamin A + Zn
      groups at 3 and 9 months were 0.34 SD and 0.37 SD, respectively, and the absolute
      difference between the vitamin A-only and Zn-only groups at 18 months was 0.31
      SD. Compared with placebo, none of the supplements affected growth. Defining
      growth faltering as a downward crossing of two or more major percentile lines, 50
      75% of the children were found to be growth faltering within 9 months of age,
      whereas 17% and 8% scored <-2 SD for WAZ and HAZ, respectively. Prenatal
      supplementation did not reduce the prevalence of growth faltering. CONCLUSIONS:
      Prenatal vitamin A supplementation had a small but significant effect on
      postnatal growth of children's length until 18 months of age compared with
      supplementation with either vitamin A + Zn or Zn alone, but not compared with
      placebo. It had no effects on other anthropometric measures and did not reduce
      the prevalence of growth faltering. Future studies should duplicate these
      findings before recommendations can be made.

PMID- 21729463
TI  - The Healthy Eating Index and the Alternate Healthy Eating Index as predictors of
      10-year CHD risk in Cuban Americans with and without type 2 diabetes.
AB  - OBJECTIVE: To examine the relationship between dietary patterns, as measured by
      the Healthy Eating Index (HEI) and the Alternate Healthy Eating Index (AHEI), and
      10-year predicted CHD risk in Cuban Americans with and without type 2 diabetes
      (T2D). DESIGN: In a cross-sectional study participants were selected from two
      randomly generated mailing lists of individuals with and without T2D. HEI and
      AHEI scores were calculated from a self-reported FFQ. CHD risk was determined
      using the 10-year CHD risk calculator of the Adult Treatment Panel III. SETTING:
      Miami Dade and Broward Counties, FL, USA. SUBJECTS: Cuban Americans (n 358) aged
      >=30 years. RESULTS: Participants with T2D had a higher waist circumference (P =
      0.001) and 10-year CHD risk score (P = 0.008) compared with those without T2D.
      Participants without T2D had a higher energy intake (P = 0.034), total blood
      cholesterol (P = 0.007), HDL cholesterol (P = 0.001) and HEI score (P = 0.006)
      compared with participants with T2D. AHEI score was a significant predictor of 10
      year CHD risk (F(1,351) = 4.44, P = 0.036). An association between AHEI and 10
      year CHD risk was found only for participants with T2D (beta = -0.244, se =
      0.049, P = 0.001).ConclusionThe present study showed that only participants with
      T2D with significantly higher AHEI scores had lower scores for 10-year predicted
      CHD risk. No association was found between HEI score and CHD risk among Cuban
      Americans. Individuals with T2D are advised to follow the AHEI dietary pattern.

PMID- 21729464
TI  - Does consuming breakfast influence activity levels? An experiment into the effect
      of breakfast consumption on eating habits and energy expenditure.
AB  - OBJECTIVE: To experimentally compare the effects of eating or skipping breakfast
      on energy expenditure, activity levels and dietary habits. DESIGN: A randomised
      cross-over trial, lasting 2 weeks. Participants were provided breakfast during
      one week and were required to fast until mid-day during the other week. SETTING:
      University campus. SUBJECTS: Forty-nine participants (twenty-six female and
      twenty-three male participants) were recruited. Food intake was monitored using
      food diaries, and energy expenditure was assessed using pedometers and heart rate
      monitors. Morningness-eveningness, physical activity and health were assessed
      using validated questionnaires. RESULTS: Across all participants, daily energy
      expenditure did not differ between the two experimental conditions. Total energy
      intake over 24 h did not vary with condition (male participants: 8134 (sd 447)
      kJ/d and 7514 (sd 368) kJ/d; female participants: 7778 (sd 410) kJ/d and 7531 (sd
      535) kJ/d, for the breakfast and no-breakfast conditions, respectively). However,
      when comparing habitual breakfast eaters with those with irregular or breakfast
      skipping habits, it was found that male non-habitual breakfast eaters consumed
      significantly (P = 0.029) more energy during the breakfast condition.
      Furthermore, female participants who were habitual breakfast eaters were found to
      eat significantly (P = 0.005) more and later in the day under the no-breakfast
      condition. CONCLUSIONS: Although the suggestion that breakfast is a behavioural
      marker for appropriate dietary and physical activity patterns is not refuted by
      the present findings, our data suggest that the effect of breakfast may vary as a
      function of gender and morning eating habits, and thus there may be other
      mechanisms that link BMI and breakfast consumption behaviour.

PMID- 21729465
TI  - Food sources of nutrients among 13-year-old Portuguese adolescents.
AB  - OBJECTIVE: To identify food sources of nutrients in adolescents' diets and to
      identify differences in food sources according to individual characteristics.
      DESIGN: A cross-sectional evaluation was carried out in the 2003/2004 school
      year. Self-administered questionnaires were used and a physical examination was
      performed. Diet was evaluated using an FFQ. SETTING: Public and private schools
      in Porto, Portugal. SUBJECTS: Adolescents aged 13 years (n 1522) enrolled at
      school. RESULTS: The main sources of energy were starchy foods (26.5 %), dairy
      (12.5 %) and meat (12.0 %). The major contributors to carbohydrate intake were
      starchy foods (38.2 %) and fruit (13.8 %) and to protein intake were meat (28.0
      %), dairy products (20.3 %), starchy foods (15.3 %) and seafood (13.6 %). The
      main sources of total fat were meat (22.0 %), starchy foods (13.4 %) and dairy
      products (12.7 %). Sweets and pastries presented important contributions to
      energy (11.1 %), carbohydrate (12.4 %), total fat (13.3 %) and saturated fat
      (16.6 %) intakes. Parental education was inversely associated with the
      contribution of sweets and pastries to energy, carbohydrate and fat intakes and
      it was positively associated with the seafood contribution to protein intake.
      CONCLUSIONS: The major sources of carbohydrates were starchy foods, which also
      accounted for a quarter of energy intake. Dairy products plus meat accounted for
      another quarter of energy. Meat was a major source of protein and fats. Sweets
      and pastries contributed more than 10 % to energy, carbohydrates, total and
      saturated fat. Parental education was the strongest determinant of food sources
      and was positively associated with a healthier contribution of food groups.

PMID- 21729466
TI  - Universal iron supplementation: a simple and effective strategy to reduce anaemia
      among low-income, postpartum women.
AB  - OBJECTIVE: To reduce prevalence of anaemia in low-income postpartum women.
      DESIGN: A randomised, non-blind clinical trial was conducted among 959 low
      income, postpartum women in eleven clinics in Mississippi. The clinics were
      randomised to one of three treatment groups: (i) selective anaemia screening of
      high-risk women as recommended currently (control); (ii) universal anaemia
      screening and treatment of anaemic women (group I); and (iii) universal Fe
      supplementation of 65 mg/d for two months to all low-income women (group II). All
      study participants within each clinic received the same treatment. Women were
      followed up at 6 months after delivery. Hb was measured at baseline and at follow
      up. The primary outcome variable was the proportion of women with anaemia after
      treatment. SETTING: Eleven health clinics in Mississippi. SUBJECTS: Low-income,
      postpartum women. RESULTS: Baseline characteristics of the three study groups
      were compared using one-way ANOVA and an appropriate post hoc test for continuous
      variables and the chi2 test for categorical variables. Fifty-two per cent of
      postpartum women were anaemic (Hb < 12.0 g/dl) and the rate decreased to 33 % at
      6 months after the intervention. Group II women, who received universal Fe
      supplementation, improved their Hb status significantly (P < 0.001) at 6 months
      postpartum compared with the other groups. Prevalence of anaemia was also
      significantly lower among group II women (22.5 %) compared with controls (34 %)
      and group I women (43 %; P < 0.001). CONCLUSIONS: A universal Fe supplementation
      strategy was effective in reducing the prevalence of anaemia among low-income
      postpartum women.

PMID- 21729467
TI  - Vitamin D and public health: an overview of recent research on common diseases
      and mortality in adulthood.
AB  - OBJECTIVE: There is increasing interest in vitamin D and its possible health
      effects. The aims of the present overview are to summarise the research on common
      diseases for which there is substantial evidence on vitamin D, identify diseases
      where vitamin D may be beneficial and discuss the public health implications of
      these findings. DESIGN: Literature search of PubMed for the years 2000 to 2010 to
      identify cohort studies with baseline measures of 25-hydroxyvitamin D (25(OH)D)
      and randomised controlled trials (RCT) of vitamin D supplementation in relation
      to fractures, colorectal cancer, CVD and all-cause mortality. Risk ratios of
      disease from comparisons between 25(OH)D quantiles in these studies were
      summarised using RevMan software version 5.1 (The Nordic Cochrane Centre,
      Copenhagen). SETTING: Community-based samples recruited into cohort studies from
      many countries. SUBJECTS: Older men and women, mostly above 50 years of age.
      RESULTS: When comparing the lowest 25(OH)D category with the highest (or
      reference), the pooled risk ratio (95 % CI) was: 1.34 (1.13, 1.59) for fractures
      from nine studies; 1.59 (1.30, 1.95) for colorectal cancer from nine studies;
      1.35 (1.17, 1.56) for CVD from twelve studies; and 1.42 (1.23, 1.63) for all
      cause mortality from twelve studies. CONCLUSIONS: Cohort studies show that
      baseline 25(OH)D levels predict increased risk of fractures, colorectal cancer,
      CVD and all-cause mortality. These associations are weak and could be explained
      by confounding variables such as obesity and physical activity. Because of their
      potential public health significance, RCT using vitamin D doses >=50 MUg/d are
      required to determine whether vitamin D protects against these diseases.

PMID- 21729468
TI  - Re-imagining the 'social' in the nutrition sciences.
AB  - OBJECTIVE: In response to The New Nutrition Science Project's Giessen
      Declaration, we provide here a case for a more fully described and integrated
      'social' dimension within the nutrition sciences. DESIGN: This paper explores
      what we mean when we argue for socially engaged nutrition sciences (SENS), and
      describes the disciplinary fields, epistemologies and methodologies that
      contribute to SENS' potential rich diversity and value. Additionally, the current
      positioning of 'social nutrition' research within the nutrition sciences is
      critiqued. RESULTS: There is fairly broad acceptance of the 'social' as an
      important contributor to successful public health nutrition situation analyses,
      intervention planning and implementation. However, we assert that the 'social' is
      not merely a contributor, the usual position, but is central. Implications for
      policy and practice that could follow from this shift in approach are outlined.
      CONCLUSIONS: We call for researchers, educators, policy makers and practitioners
      alike to re-imagine the role and purpose of social science enquiry that could
      enable the delivery of more socially engaged nutrition sciences.

PMID- 21729469
TI  - Perceptions of portion size and energy content: implications for strategies to
      affect behaviour change.
AB  - OBJECTIVE: To assess Australian consumers' perception of portion size of fast
      food items and their ability to estimate energy content. DESIGN: Cross-sectional
      computer-based survey. SETTING: Australia. SUBJECTS: Fast-food consumers (168
      male, 324 female) were asked to recall the items eaten at the most recent visit
      to a fast-food restaurant, rate the prospective satiety and estimate the energy
      content of seven fast-food or 'standard' meals relative to a 9000 kJ Guideline
      Daily Amount. Nine dietitians also completed the energy estimation task. RESULTS:
      Ratings of prospective satiety generally aligned with the actual size of the
      meals and indicated that consumers perceived all meals to provide an adequate
      amount of food, although this differed by gender. The magnitude of the error in
      energy estimation by consumers was three to ten times that of the dietitians. In
      both males and females, the average error in energy estimation for the fast-food
      meals (females: mean 3911 (sd 1998) kJ; males: mean 3382 (sd 1957) kJ) was
      significantly (P < 0.001) larger than for the standard meals (females: mean 2607
      (sd 1623) kJ; males: mean 2754 (sd 1652) kJ). In women, error in energy
      estimation for fast-food items predicted actual energy intake from fast-food
      items (beta = 0.16, P < 0.01). CONCLUSIONS: Knowledge of the energy content of
      standard and fast-food meals in fast-food consumers in Australia is poor.
      Awareness of dietary energy should be a focus of health promotion if nutrition
      information, in its current format, is going to alter behaviour.

PMID- 21729470
TI  - A pilot study of a telephone-based parental intervention to increase fruit and
      vegetable consumption in 3-5-year-old children.
AB  - OBJECTIVE: To examine the potential efficacy of a brief telephone-based parental
      intervention in increasing fruit and vegetable consumption in children aged 3-5
      years and to examine the feasibility of intervention delivery and acceptability
      to parents. DESIGN: A pre-post study design with no comparison group. Telephone
      surveys were conducted approximately 1 week before and following intervention
      delivery. SETTING: Participants were recruited through pre-schools in the Hunter
      region, New South Wales, Australia. SUBJECTS: Thirty-four parents of 3-5-year
      olds received four 30-min interventional telephone calls over 4 weeks
      administered by trained telephone interviewers. The scripted support calls
      focused on fruit and vegetable availability and accessibility within the home,
      parental role modelling of fruit and vegetable consumption and on implementing
      supportive family eating routines. RESULTS: Following the intervention, the
      frequency and variety of fruit and vegetable consumption increased (P = 0.027),
      as measured by a subscale of the children's dietary questionnaire. The
      intervention was feasible to be delivered to parents, as all participants who
      started the intervention completed all four calls, and all aspects of the
      interventional calls, including the number, length, content, format and
      relevance, were considered acceptable by more than 90 % of parents. CONCLUSIONS:
      A brief telephone-based parental intervention to encourage fruit and vegetable
      consumption in pre-school-aged children may be effective, feasible and
      acceptable. Further investigation is warranted in a randomised controlled trial.

PMID- 21729471
TI  - Beverage intake patterns of Canadian children and adolescents.
AB  - OBJECTIVE: Little is known of the beverage intake patterns of Canadian children
      or of characteristics within these patterns. The objective was to determine
      beverage intake patterns among Canadian children and compare intakes of fourteen
      types of beverages, along with intakes of vitamin C and Ca, and sociodemographic
      factors across clusters. DESIGN: Dietary information was collected using one 24 h
      recall. Sociodemographic data were collected by interview. Cluster analysis was
      used to determine beverage intake patterns. Pearson's chi2 and 95 % CI were used
      to test differences across clusters. SETTING: Data from the Canadian Community
      Health Survey Cycle 2.2. SUBJECTS: Children aged 2-18 years with plausible energy
      intake and complete sociodemographic data (n 10 038) were grouped into the
      following categories: 2-5-year-old boys and girls, 6-11-year-old girls, 6-11-year
      old boys, 12-18-year-old girls and 12-18-year-old boys. RESULTS: Five beverage
      clusters emerged for children aged 2-5 years, six clusters for children aged 6-11
      years (both sexes) and four clusters for those aged 12-18 years (both sexes).
      Sweetened beverage clusters appeared in all age-sex groups. Intakes of sweetened
      beverages ranged from 553 to 1059 g/d and contributed between 2 % and 18 % of
      total energy intake. Girls 6-11 years of age in the 'soft drink' cluster had
      lower Ca intake compared with other clusters in that age-sex group. Age and
      ethnicity differed across clusters for most age-sex groups. Differences for
      household food security status and income were found; however, no pattern
      emerged. CONCLUSIONS: Patterns in beverage intake among Canadian children include
      beverages that are predominantly sugar sweetened. Public health nutrition
      professionals can use knowledge about beverage patterns among children, as well
      as the characteristics of these groups, in the development of nutritional
      programmes and policies.

PMID- 21729472
TI  - Nutrient and food intakes differ among Latina subgroups during pregnancy.
AB  - OBJECTIVE: To document nutrient and food group serving intakes from food sources
      among Latina subgroups living in the same geographical area. DESIGN: A cross
      sectional study. Nutrient and food group serving intakes were assessed by means
      of a 24 h recall administered immediately after a prenatal survey. SETTING:
      Hartford, CT, USA. SUBJECTS: A total of 233 low-income pregnant Latinas. For
      analyses, Latinas were classified into two groups on the basis of self-reported
      ethnic identity: Puerto Ricans and non-Puerto Rican Latinas. RESULTS: Puerto
      Rican Latinas were more likely than non-Puerto Rican Latinas to be more
      acculturated and to consume foods (i.e. processed meat, cheese, soft drinks) and
      higher levels of nutrients (i.e. fat, SFA, MUFA, trans fatty acids) that have
      been implicated in the development of chronic diseases. By contrast, non-Puerto
      Rican Latinas were more likely to consume foods (i.e. fruits, dark green/yellow
      vegetables, tomatoes, non-starchy vegetables) and higher levels of nutrients
      (i.e. fibre, vegetable protein, folate, beta-carotene) that promote health when
      compared with Puerto Rican Latinas. CONCLUSIONS: Findings suggest that
      acculturation may play a role in dietary intake. Clinicians and dietitians need
      to be aware of these differences to encourage healthy eating patterns among more
      acculturated pregnant Latina clients.

PMID- 21729473
TI  - Sociodemographic, health and lifestyle predictors of poor diets.
AB  - OBJECTIVE: Poor-quality diet, regarded as an important contributor to health
      inequalities, is linked to adverse health outcomes. We investigated
      sociodemographic and lifestyle predictors of poor-quality diet in a population
      sample. DESIGN: A cross-sectional analysis of the Survey of Lifestyle, Attitudes
      and Nutrition (SLAN). Diet was assessed using an FFQ (n 9223, response rate =
      89%), from which a dietary score (the DASH (Dietary Approaches to Stop
      Hypertension) score) was constructed. SETTING: General population of the Republic
      of Ireland. SUBJECTS: The SLAN survey is a two-stage clustered sample of 10,364
      individuals aged 18 years. RESULTS: Adjusting for age and gender, a number of
      sociodemographic, lifestyle and health-related variables were associated with
      poor-quality diet: social class, education, marital status, social support, food
      poverty (FP), smoking status, alcohol consumption, underweight and self-perceived
      general health. These associations persisted when adjusted for age, gender and
      social class. They were not significantly altered in the multivariate analysis,
      although the association with social support was attenuated and that with FP was
      borderline significant (OR = 1.2, 95% CI 1.03, 1.45). A classical U-shaped
      relationship between alcohol consumption and dietary quality was observed.
      Dietary quality was associated with social class, educational attainment, FP and
      related core determinants of health. CONCLUSIONS: The extent to which social
      inequalities in health can be explained by socially determined differences in
      dietary intake is probably underestimated. The use of composite dietary quality
      scores such as the DASH score to address the issue of confounding by diet in the
      relationship between alcohol consumption and health merits further study.

PMID- 21729474
TI  - What's in the lunchbox? Dietary behaviour of learners from disadvantaged schools
      in the Western Cape, South Africa.
AB  - OBJECTIVE: To identify and describe factors associated with food shop (known as
      tuck shop in South Africa) and lunchbox behaviours of primary-school learners in
      South Africa. DESIGN: Analysis of data collected in 2008 from a cross-sectional
      survey. SETTING: Sixteen primary schools in the Western Cape, South Africa.
      SUBJECTS: A total of 717 grade 4 learners aged 10-12 years. RESULTS: A 24 h
      recall established that 69 % of learners carried a lunchbox to school and 49 %
      had consumed at least one item purchased from the school food shop/vendor. Most
      lunchboxes contained white bread with processed meat, whereas the most frequent
      food shop/vendor purchase comprised chips/crisps. Learners who carried a lunchbox
      to school had significantly lower BMI percentiles (P = 0.002) and BMI-for-age (P
      = 0.034), compared with their counterparts. Moreover, they were younger, had
      higher standard-of-living and dietary diversity scores, consumed more meals per
      day, had greater self-efficacy and came from predominantly urban schools,
      compared with those who did not carry a lunchbox to school. Learners who ate food
      shop/vendor purchases had a lower standard-of-living score and higher dietary
      diversity and meal scores. Only 2 % of learners were underweight, whereas 19 %
      were stunted and 21 % were overweight/obese (BMI >= 25 kg/m2). CONCLUSIONS:
      Children who carried a lunchbox to school appeared to have greater dietary
      diversity, consumed more regular meals, had a higher standard of living and
      greater nutritional self-efficacy compared with those who did not carry a
      lunchbox to school.

PMID- 21729475
TI  - Fruit and vegetable intakes in relation to plasma nutrient concentrations in
      women in Shanghai, China.
AB  - OBJECTIVE: To evaluate the validity of fruit and vegetable intakes as it relates
      to plasma carotenoid and vitamin C concentrations in Chinese women, using three
      classification schemes. DESIGN: Intakes were calculated using an interviewer
      administered FFQ. Fruits and vegetables, botanical groups and high-nutrient
      groups were evaluated. These three classification schemes were compared with
      plasma carotenoid and vitamin C concentrations from blood samples collected
      within 1 week of questionnaire completion. SETTING: Shanghai, China. SUBJECTS:
      Participants (n 2031) comprised women who had participated in a case-control
      study of diet and breast-related diseases nested within a randomized trial of
      breast self-examination among textile workers (n 266 064) RESULTS: Fruit intake
      was significantly (P < 0.05) and positively associated with plasma concentrations
      of alpha-tocopherol, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene,
      retinyl palmitate and vitamin C. Fruit intake was inversely associated with gamma
      tocopherol and lutein + zeaxanthin concentrations. Vegetable consumption was
      significantly and positively associated with gamma-tocopherol and beta
      cryptoxanthin concentrations. Each botanical and high-nutrient group was also
      significantly associated with particular plasma nutrient concentrations. Fruit
      and vegetable intakes and most plasma nutrient concentrations were significantly
      associated with season of interview. CONCLUSIONS: These results suggest that the
      manner in which fruits and vegetables are grouped leads to different plasma
      nutrient exposure information, which may be an important consideration when
      testing and generating hypotheses regarding disease risk in relation to diet.
      Interview season should be considered when evaluating the associations of
      reported intake and plasma nutrients with disease outcomes.

PMID- 21729476
TI  - Fast-food outlets and walkability in school neighbourhoods predict fatness in
      boys and height in girls: a Taiwanese population study.
AB  - OBJECTIVE: There is increasing evidence that the school food environment
      contributes to childhood obesity and health in various locations. We investigated
      the influence of fast-food stores and convenience food stores (FS and CS,
      respectively) on growth and body composition in a range of residential densities
      for North-east Asian food culture. DESIGN: Anthropometrics and birth weight of
      schoolchildren were obtained. Geocoded mapping of schools and food outlets was
      conducted. Multivariable linear regression models, adjusted for father's
      ethnicity and education, as well as for household income, pocket money, birth
      weight, physical activity, television watching, food quality and region, were
      used to predict body composition from school food environments. SETTING:
      Elementary schools and school neighbourhoods in 359 townships/districts of
      Taiwan. SUBJECTS: A total of 2283 schoolchildren aged 6-13 years from the
      Elementary School Children's Nutrition and Health Survey in Taiwan conducted in
      2001-2002. RESULTS: Remote and socially disadvantaged locations had the highest
      prevalence of lower weight, BMI, waist circumference and triceps skinfold
      thickness. Food store densities, FS and CS, were highest in urban Taiwan and
      lowest in remote Taiwan. In the fully adjusted models, FS densities predicted
      weight and BMI in boys; there was a similar association for waist circumference,
      except when adjusted for region. FS densities also predicted height for girls.
      Except for weight and BMI in boys, CS did not have effects evident with FS for
      either boys or girls. CONCLUSIONS: A high FS density, more than CS density, in
      Taiwan increased the risk of general (BMI) and abdominal (waist circumference)
      obesity in boys and stature in girls. These findings have long-term implications
      for chronic disease in adulthood.

PMID- 21729477
TI  - Renal impairment and moderate alcohol consumption in the elderly. Results from
      the Italian Longitudinal Study on Aging (ILSA).
AB  - OBJECTIVE: The influence of moderate alcohol consumption on renal function is not
      clear in elderly people. The aim of the present study was to investigate the
      relationship between alcohol consumption and renal function, expressed as serum
      creatinine levels and glomerular filtration rates (GFR), in an elderly
      population. DESIGN: Perspective cohort study. SETTING: Population-based study on
      an elderly Italian population. SUBJECTS: A sample of 3404 Italian people (1619
      women and 1785 men), aged 65-84 years, from the Italian Longitudinal Study on
      Aging (ILSA). RESULTS: Prevalence and cumulative risk of impaired renal function
      (defined as GFR <= 60 ml/min) were estimated by sex and alcohol consumption
      groups. Logistic regression analysis adjusting for confounders (age, education,
      smoking, BMI and medications) and intermediate factors (blood cholesterol and
      fibrinogen, systolic hypertension and diabetes) showed that alcohol consumption
      level was not significantly related to the prevalence of mild renal impairment in
      elderly women. In men, both prevalence and incidence results seemed to suggest an
      inverse linear relationship between moderate alcohol consumption and the risk of
      mild renal impairment. A U-shaped association was shown for women at the
      incidence phase, suggesting a higher risk of developing renal impairment for
      women who drink more than 24 g alcohol/d. CONCLUSIONS: Our results suggest that,
      in accordance with the recommendations on alcohol consumption in the elderly,
      moderate quantities of alcohol are not injurious to renal function in elderly
      men.

PMID- 21729478
TI  - Dietary interventions for weight loss and cardiovascular risk reduction in people
      of African ancestry (blacks): a systematic review.
AB  - OBJECTIVE: To systematically review weight and cardiovascular risk reduction in
      blacks by diet and lifestyle changes. DESIGN: Randomised and non-randomised
      controlled trials of diet with/without lifestyle changes with duration of
      intervention >=3 months, and published between January 1990 and December 2009,
      were searched in electronic databases including MEDLINE, EMBASE, CINAHL and CCTR
      (Cochrane Controlled Trials Register). Studies were included if they reported
      weight/BMI changes with changes in at least one of the following: systolic and
      diastolic blood pressure, fasting plasma lipids and glucose, and glycated
      haemoglobin. SETTING: Clinical, community and church-based interventions.
      SUBJECTS: Study participants were of African ancestry (blacks). RESULTS: Eighteen
      studies met the inclusion criteria. Average mean difference in weight loss was 
      2.66 kg, with improvements in all outcomes except total cholesterol. No
      significant difference was observed in outcome measures between all studies and
      studies that recruited only healthy participants or patients with type 2
      diabetes. CONCLUSIONS: Diet and lifestyle changes result in weight loss with
      improvements in cardiovascular risk factors in blacks. However, more culturally
      tailored programmes have been suggested to motivate and encourage blacks to
      participate in intervention trials.

PMID- 21729479
TI  - Parent calcium-rich-food practices/perceptions are associated with calcium intake
      among parents and their early adolescent children.
AB  - OBJECTIVE: The study aimed to (i) segment parents of early adolescents into
      subgroups according to their Ca-rich-food (CRF) practices and perceptions
      regarding early adolescent CRF intake and (ii) determine whether Ca intake of
      parents and early adolescents differed by subgroup. DESIGN: A cross-sectional
      convenience sample of 509 parents and their early adolescent children completed a
      questionnaire in 2006-2007 to assess parent CRF practices and perceptions and to
      estimate parent and child Ca intakes. SETTING: Self-administered questionnaires
      were completed in community settings or homes across nine US states. SUBJECTS:
      Parents self-reporting as Asian, Hispanic or non-Hispanic White with a child aged
      10-13 years were recruited through youth or parent events. RESULTS: Three parent
      CRF practice/perception segments were identified, including 'Dedicated-Milk
      Providers/Drinkers' (49 %), 'Water Regulars' (30 %) and 'Sweet-Drink-Permissive
      Parents' (23 %). Dedicated-Milk Providers/Drinkers were somewhat older and more
      likely to be non-Hispanic White than other groups. Ca intakes from all food
      sources, milk/dairy foods and milk only, and milk intakes, were higher among
      early adolescent children of Dedicated-Milk Providers/Drinkers compared with
      early adolescents of parents in other segments. Soda pop intakes were highest for
      early adolescents with parents in the Water Regulars group than other groups.
      Dedicated-Milk Providers/Drinkers scored higher on culture/tradition, health
      benefits and ease of use/convenience subscales and lower on a dairy/milk
      intolerance subscale and were more likely to report eating family dinners daily
      than parents in the other groups. CONCLUSIONS: Parent education programmes should
      address CRF practices/perceptions tailored to parent group to improve Ca intake
      of early adolescent children.

PMID- 21729480
TI  - Nutritional policies and standards for snacks served in after-school programmes:
      a review.
AB  - OBJECTIVE: To review and synthesize existing national and state organizations'
      policies related to the nutritional quality of snacks served in after-school
      programmes (ASP; 15.00-18.00 hours) in the USA. DESIGN: Systematic review of
      websites and corresponding documentation describing national and state-level ASP
      organizations' policies, standards, guidelines and/or recommendations for the
      nutritional quality of snacks served within the ASP setting. SETTING: ASP can
      play a critical role in a child's daily dietary intake. State and national
      organizations have developed policies to assist ASP in selecting nutritionally
      appropriate snacks, yet no widely accepted standards exist. By reviewing the
      extent of existing policies, recommendations for uniform policies can be made.
      SUBJECTS: Policy documentation. RESULTS: A total of seventeen organizations
      representing five unique snack policies comprised of thirteen different food
      items were identified. The most widely recognized snack policy, which the
      majority of state and national ASP organizations endorsed and upon which other
      snack policies were modelled, was the US Department of Agriculture reimbursement
      programmes. Consistently, policies endorsed serving fruits/vegetables, whole
      grains and milk/dairy products, and limiting foods high in fats/sugar/energy
      (calories). Two policies focused predominantly on total energy and macronutrient
      composition of snacks, a single policy suggested limits on sugar-sweetened
      beverages, and three endorsed serving water daily. A proposed set of general
      guidelines for ASP was developed based on uniformity in recommendations across
      policies. CONCLUSIONS: The proposed set of nutritional guidelines will assist
      policy makers and ASP providers in selecting and serving nutritionally
      appropriate snacks that contribute to a child's overall healthful daily dietary
      intake.

PMID- 21729481
TI  - Development and evaluation of the Oxford WebQ, a low-cost, web-based method for
      assessment of previous 24 h dietary intakes in large-scale prospective studies.
AB  - OBJECTIVES: To describe the development of the Oxford WebQ, a web-based 24 h
      dietary assessment tool developed for repeated administration in large
      prospective studies; and to report the preliminary assessment of its performance
      for estimating nutrient intakes. DESIGN: We developed the Oxford WebQ by repeated
      testing until it was sufficiently comprehensive and easy to use. For the latest
      version, we compared nutrient intakes from volunteers who completed both the
      Oxford WebQ and an interviewer-administered 24 h dietary recall on the same day.
      SETTING: Oxford, UK. SUBJECTS: A total of 116 men and women. RESULTS: The WebQ
      took a median of 12.5 (interquartile range: 10.8-16.3) min to self-complete and
      nutrient intakes were estimated automatically. By contrast, the interviewer
      administered 24 h dietary recall took 30 min to complete and 30 min to code.
      Compared with the 24 h dietary recall, the mean Spearman's correlation for the 21
      nutrients obtained from the WebQ was 0.6, with the majority between 0.5 and 0.9.
      The mean differences in intake were less than +/-10 % for all nutrients except
      for carotene and vitamins B12 and D. On rare occasions a food item was reported
      in only one assessment method, but this was not more frequent or systematically
      different between the methods. CONCLUSIONS: Compared with an interviewer-based 24
      h dietary recall, the WebQ captures similar food items and estimates similar
      nutrient intakes for a single day's dietary intake. The WebQ is self-administered
      and nutrients are estimated automatically, providing a low-cost method for
      measuring dietary intake in large-scale studies.

PMID- 21729482
TI  - Intakes and perceived home availability of sugar-sweetened beverages, fruit and
      vegetables as reported by mothers, fathers and adolescents in the HEIA (HEalth In
      Adolescents) study.
AB  - OBJECTIVE: To investigate the intakes of sugar-sweetened beverages (SSB), fruit
      and vegetables (FV) among adolescents and their parents and to explore
      differences in the perceived availability by gender and parental education.
      DESIGN: Baseline data from the HEIA (HEalth In Adolescents) study. SETTING: Data
      on intake of SSB were collected assessing frequency and amounts, whereas
      consumption of FV was assessed on the basis of frequency. Further, perceived
      availability at home and at school (taken from home) was reported. SUBJECTS:
      Participants were 1528 Norwegian adolescents aged 11 years, as well as 1200
      mothers and 1057 fathers. RESULTS: The adolescents' intake of SSB was low on
      weekdays but doubled during weekend days. This pattern was observed among parents
      as well. There were significant differences in intake between boys, girls,
      mothers and fathers, except for vegetables. Fathers reported the lowest frequency
      of FV intake. Compared with adolescents, mothers reported lower availability of
      SSB and higher availability of FV. Compared with their sons, fathers reported
      higher availability of vegetables and lower availability of sugar-sweetened fruit
      drinks at school. Significant differences in adolescents' intake of SSB and in
      the perceived availability of both SSB and FV by parental education were found.
      CONCLUSIONS: The intake of SSB was higher during weekend days than during
      weekdays, whereas the frequency of FV intake was low. Differences in adolescents'
      perceived availability of both SSB and FV on the basis of parental education were
      found, whereas the differences in intake were significant only for SSB.
      Increasing parental awareness of availability and their potential as role models
      across parental gender and educational level could improve adolescents' dietary
      habits.

PMID- 21729483
TI  - Accuracy and correlates of visual and verbal instruments assessing maternal
      perceptions of children's weight status: the Healthy Growth Study.
AB  - OBJECTIVE: To examine the accuracy of maternal ability to classify their
      children's weight status correctly using a verbal and a visual classification
      instrument and to detect significant correlates of maternal misperceptions.
      DESIGN: Cross-sectional study. SETTING: Primary schools in four counties from
      north, west, central and south Greece. SUBJECTS: A representative sample of 1858
      primary-school children aged 9-13 years was examined. Two different instruments
      to assess maternal perceptions of their children's weight status, i.e. a verbal
      and a visual one, were used. RESULTS: Verbal and visual maternal underestimation
      rates of children's weight status were 15.0 % and 41.3 %, respectively. The
      frequency of underestimation was much higher among overweight and obese children
      for both instruments. The highest underestimation rates of 87.9 % and 82.1 % in
      overweight and obese boys, respectively, were obtained with the visual
      instrument. Multiple logistic regression modelling revealed that the likelihood
      of both verbal and visual maternal underestimation of their children's weight
      status was significantly higher for overweight mothers and for those with a lower
      educational level. Furthermore, children's male gender and a nanny or someone
      other than the mother as the child's primary caregiver were found to increase the
      odds of visual and verbal maternal underestimation of children's weight status,
      respectively. CONCLUSIONS: The present study showed that the verbal instrument
      used to assess maternal perceptions of their children's weight status was more
      accurate compared with the visual one. However, both instruments showed that a
      considerable number of overweight and obese boys had their weight status
      underestimated by their mothers. Educating mothers to classify their children's
      weight status correctly might be a key factor for the implementation of
      successful childhood obesity prevention initiatives.

PMID- 21729484
TI  - Association between adiposity indices and cardiometabolic risk factors among
      adults living in Puerto Rico.
AB  - OBJECTIVE: To compare the general adiposity index (BMI) with abdominal obesity
      indices (waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height
      ratio (WHtR)) in order to examine the best predictor of cardiometabolic risk
      factors among Hispanics living in Puerto Rico. DESIGN: Secondary analysis of
      measurements taken from a representative sample of adults. Logistic regression
      models (prevalence odds ratios (POR)), partial Pearson's correlations
      (controlling for age and sex) and receiver-operating characteristic (ROC) curves
      were calculated between indices of obesity (BMI, WC, WHR and WHtR) and blood
      pressure, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), total cholesterol
      (TC):HDL-C, TAG, fasting blood glucose, glycosylated Hb, high-sensitivity C
      reactive protein (hs-CRP), fibrinogen, plasminogen activator inhibitor-1 (PAI-1)
      and an aggregated measure of cardiometabolic risk. SETTING: Household study
      conducted between 2005 and 2007 in the San Juan Metropolitan Area in Puerto Rico.
      SUBJECTS: A representative sample of 858 non-institutionalized adults. RESULTS:
      All four obesity indices significantly correlated with the cardiometabolic risk
      factors. WHtR had the highest POR for high TC:HDL-C, blood pressure, hs-CRP,
      fibrinogen and PAI-1; WC had the highest POR for low HDL-C and high LDL-C and
      fasting blood glucose; WHR had the highest POR for overall cardiometabolic risk,
      TAG and glycosylated Hb. BMI had the lowest POR for most risk factors and
      smallest ROC curve for overall cardiometabolic risk. CONCLUSIONS: The findings of
      the study suggest that general adiposity and abdominal adiposity are both
      associated with cardiometabolic risk in this population, although WC, WHR and
      WHtR appear to be slightly better predictors than BMI.

PMID- 21729485
TI  - Parental eating attitudes and indicators of healthy eating in a longitudinal
      randomized dietary intervention trial (the STRIP study).
AB  - OBJECTIVE: To examine the effects of child-oriented dietary intervention on
      parental eating attitudes and dietary behaviour. DESIGN: In the prospective,
      randomized Special Turku Coronary Risk Factor Intervention Project for Children
      (the STRIP study), a cohort of Finnish families took part in a nutritional
      intervention trial focused on the quality of their children's fat intake since
      the age of 8 months. Health-related and hedonic eating attitudes of the parents
      were measured after 10 years of dietary intervention using a validated Health and
      Taste Attitude Scales (HTAS) questionnaire (n 660). Parents' eating behaviour was
      studied using a 1 d food record (n 491). SETTING: Finland. SUBJECTS: Mothers and
      fathers (n 660) of the STRIP children. RESULTS: The parents of the intervention
      families had a higher level of interest in healthy eating compared with control
      parents. The interest in natural products or hedonic eating attitudes did not
      differ between the groups. The parents' general health interest was associated
      with low saturated fat intake, fruit and vegetable consumption, fibre intake and
      seeking pleasure in eating, but it was not associated with BMI. The intervention
      also improved the quality of dietary fat among parents with the lowest level of
      interest in healthy eating. CONCLUSIONS: Parents' general health interest was
      associated with regular dietary counselling as well as with healthier food choice
      behaviour. However, the dietary intervention that focused especially on the
      quality of the child's fat intake also enhanced specific changes in the family's
      fat consumption without a high level of interest in healthy eating.

PMID- 21729486
TI  - Severe physical violence between intimate partners during pregnancy: a risk
      factor for early cessation of exclusive breast-feeding.
AB  - OBJECTIVE: To investigate the role of severe physical violence during pregnancy
      (SPVP) between intimate partners in early cessation of exclusive breast-feeding
      (EBF). DESIGN: A health services survey. The revised Conflict Tactics Scale was
      used to characterize SPVP; premature breast-feeding cessation was identified
      using a current status data approach, which was based on the information reported
      from food recall during the preceding 7 d. The cumulative hazard function was
      estimated by complementary log-log transformation models, which allowed the
      ensuing estimation of early breast-feeding cessation rates in different age
      groups and the ratio of rates of weaning between women exposed and not exposed to
      violence. SETTING: Five large public primary health-care facilities of Rio de
      Janeiro, Brazil. SUBJECTS: The sample comprised 811 randomly selected mothers of
      children under 5 months of age who were waiting to be consulted. RESULTS: SPVP is
      an independent risk factor of cessation of EBF since, after controlling for socio
      economic, demographic, reproductive and lifestyle variables, women exposed to
      violence presented an incidence density that was 31% higher than those who were
      not exposed (hazard ratio = 1.30, 95% CI 1.01, 1.69). CONCLUSIONS: The findings
      corroborate the hypothesis that SPVP is an important risk factor for EBF. This
      indicates the need for incentives to adequately train health-care personnel in
      dealing with lactating women in order to gain a broader view of breast-feeding
      beyond the biological aspects of lactation, including the maternal psychological
      dimension.

PMID- 21729487
TI  - Fermented soyabean and vitamin C-rich fruit: a possibility to circumvent the
      further decrease of iron status among iron-deficient pregnant women in Indonesia.
AB  - OBJECTIVE: Increasing the consumption of Fe-rich foods and thus improving Fe
      bioavailability without significantly increasing diet cost is the most
      sustainable intervention for improving Fe intake. We assessed the effect of
      supplementary food consisting of fermented soyabean (tempeh) and vitamin C-rich
      fruit consumed during pregnancy on maternal iron deficiency (ID). DESIGN:
      Pregnant women were randomly allocated by village into optimized diet and control
      groups. Supplementary food was given 6 d/week at home. The average weekly food
      provided comprised 600 g of tempeh, 30 g of meat, 350 g of guava, 300 g of papaya
      and 100 g of orange. Hb, ferritin and transferrin receptor (TfR) concentrations
      were measured at 12-20 and at 32-36 weeks of gestation. SETTING: Thirty-nine
      villages in Indonesia. SUBJECTS: Pregnant women (12-20 weeks of gestation, n
      252). RESULTS: At baseline, mean Hb, ferritin and TfR concentrations and body Fe
      concentration were within the normal range and did not differ between groups. At
      near term, mean Hb, ferritin and body Fe decreased, whereas mean TfR increased
      significantly in both groups. The mean changes in Fe status were similar in both
      groups. In Fe-deficient women, consumption of an optimized diet was associated
      with smaller decreases in Hb (1.02 (95% CI 0.98, 1.07) g/l; P = 0.058), ferritin
      (1.42 (95% CI 1.16, 1.75) MUg/l; P = 0.046) and body Fe (2.57 (95% CI 1.71, 3.43)
      mg/kg; P = 0.073) concentrations, compared with a state of no intervention. Fe
      deficient women at baseline benefited more from supplementary food compared with
      Fe-replete women. CONCLUSIONS: Daily supplementary food containing tempeh and
      vitamin C-rich fruits during pregnancy might have positive effects on maternal
      ID.

PMID- 21729488
TI  - Nursery nutrition in Liverpool: an exploration of practice and nutritional
      analysis of food provided.
AB  - OBJECTIVE: To explore nutrition and food provision in pre-school nurseries in
      order to develop interventions to promote healthy eating in pre-school settings.
      DESIGN: Quantitative data were gathered using questionnaires and professional
      menu analysis. SETTING: In the community, at pre-school nurseries. SUBJECTS: All
      130 nurseries across Liverpool were a sent questionnaire (38 % response rate);
      thirty-four menus were returned for analysis (26 % response rate). RESULTS: Only
      21 % of respondents stated they had adequate knowledge on nutrition for pre
      school children. Sixty-one per cent of cooks reported having received only a
      'little' advice on healthy eating and this was often not specific to under-5 s
      nutrition. Fifty-seven per cent of nurseries did not regularly assess their menus
      for nutritional quality. The menu analysis revealed that all menus were deficient
      in energy, carbohydrate, Fe and Zn. Eighty-five per cent of nurseries had Na/salt
      levels which exceed guidelines. CONCLUSIONS: Nurseries require support on healthy
      eating at policy, knowledge and training levels. This support should address
      concerns relating to both menu planning and ingredients used in food provision
      and meet current guidelines on food provision for the under-5 s.

PMID- 21729489
TI  - The potential role of small fish species in improving micronutrient deficiencies
      in developing countries: building evidence.
AB  - OBJECTIVE: To build a comprehensive overview of the potential role of fish in
      improving nutrition with respect to certain micronutrient deficiencies in
      developing countries. DESIGN: A comprehensive literature review was completed.
      For this the electronic library databases ASFA, CABD and Scopus were
      systematically searched and relevant references cited in these sources were
      carefully analysed. The search terms used were 'fish', 'small fish species',
      'micronutrients', 'food-based strategies', 'fish consumption' and 'developing
      countries'. The quality of data on nutritional analyses was carefully reviewed
      and data that lacked proper information on methods, units and samples were
      excluded. RESULTS: The evidence collected confirmed the high levels of vitamin A,
      Fe and Zn in some of the small fish species in developing countries. These small
      fish are reported to be more affordable and accessible than the larger fish and
      other usual animal-source foods and vegetables. Evidence suggests that these
      locally available small fish have considerable potential as cost-effective food
      based strategies to enhance micronutrient intakes or as a complementary food for
      undernourished children. However, the present review shows that only a few
      studies have been able to rigorously assess the impact of fish consumption on
      improved nutritional status in developing countries. CONCLUSIONS: Further
      research is required in areas such as determination of fish consumption patterns
      of poor households, the nutritional value of local fish and other aquatic animals
      and the impact of fish intake on improved nutritional status in developing
      countries where undernutrition is a major public health problem.

PMID- 21729490
TI  - Choosing front-of-package food labelling nutritional criteria: how smart were
      'Smart Choices'?
AB  - OBJECTIVE: The 'Smart Choices' programme was an industry-driven, front-of-package
      (FOP) nutritional labelling system introduced in the USA in August 2009,
      ostensibly to help consumers select healthier options during food shopping. Its
      nutritional criteria were developed by members of the food industry in
      collaboration with nutrition and public health experts and government officials.
      The aim of the present study was to test the extent to which products labelled as
      'Smart Choices' could be classified as healthy choices on the basis of the
      Nutrient Profile Model (NPM), a non-industry-developed, validated nutritional
      standard. DESIGN: A total of 100 packaged products that qualified for a 'Smart
      Choices' designation were sampled from eight food and beverage categories. All
      products were evaluated using the NPM method. RESULTS: In all, 64 % of the
      products deemed 'Smart Choices' did not meet the NPM standard for a healthy
      product. Within each 'Smart Choices' category, 0 % of condiments, 8.70 % of fats
      and oils, 15.63 % of cereals and 31.58 % of snacks and sweets met NPM thresholds.
      All sampled soups, beverages, desserts and grains deemed 'Smart Choices' were
      considered healthy according to the NPM standard. CONCLUSIONS: The 'Smart
      Choices' programme is an example of industries' attempts at self-regulation. More
      than 60 % of foods that received the 'Smart Choices' label did not meet standard
      nutritional criteria for a 'healthy' food choice, suggesting that industries'
      involvement in designing labelling systems should be scrutinized. The NPM system
      may be a good option as the basis for establishing FOP labelling criteria,
      although more comparisons with other systems are needed.

PMID- 21729491
TI  - Social, attitudinal and behavioural correlates of fruit and vegetable consumption
      among Cypriot adolescents.
AB  - OBJECTIVE: To examine the prevalence and correlates of fruit and vegetable (FV)
      consumption in Cypriot adolescents. DESIGN: A cross-sectional study. SETTING: The
      Republic of Cyprus. SUBJECTS: A total of 1966 adolescents with a mean age of 14.7
      (SD 2.2) years from nine elementary (n 448), six middle (n 657), five high (n
      475) and five technical/vocational schools (n 386) in Cyprus. Participants
      completed a questionnaire assessing FV consumption using a two-item screening
      measure and a number of social, attitudinal and behavioural correlates of FV
      consumption. RESULTS: Overall, 19.3% of adolescents reported consuming five or
      more portions of FV daily, with elementary and middle school students more likely
      to meet recommendations (23.8% and 24.4%, respectively) compared with high and
      technical/vocational school students (14.0% and 12.5%, respectively). Consuming
      five or more portions of FV was associated with preference for FV (OR = 2.2),
      family eating patterns (OR = 1.5), friends' FV consumption (OR = 1.2) and school
      support for FV consumption (OR = 0.8). Consuming at least one portion of fruit
      daily was significantly associated with preference for FV (OR = 2.0) and family
      eating patterns (OR = 1.7). Consuming at least one portion of vegetables daily
      was associated with preference for FV (OR = 4.2) and eating while watching
      television (OR = 0.8). CONCLUSIONS: Targeting individual and family-based
      components may enhance the effectiveness of intervention programmes to promote FV
      consumption.

PMID- 21729492
TI  - The profile of the Greek 'XXL' family.
AB  - OBJECTIVE: To identify Greek families in which all members were overweight or
      obese (XXL families) and to describe their profile with regard to their socio
      economic status and their eating behaviours and practices. DESIGN: A prospective
      cohort study. SETTING: The metropolitan area of Kavala. SUBJECTS: We recruited
      children aged 11 and 12 years from twelve primary schools, and their parents,
      from volunteers. Auxologic measurements of the children included height and
      weight. A structured questionnaire pertaining to information on the socio
      economic status of the family, anthropometric values and educational status of
      parents, dietary habits and the availability of various food products and
      beverages at home, as well as dietary intake, physical activity, time spent
      sleeping and time spent watching television, was filled in by one of the parents
      of each child. A total of 331 families finally participated. RESULTS: In sixty
      one families (18.43 %) both parents and child were either overweight or obese
      (XXL family), and in seven of these families all members were obese. Only twenty
      eight families (8.46 %) had all members with a normal BMI. The XXL family was
      associated with lower educational status of both parents, whereas a higher
      percentage of XXL families resided in rural areas and had lower income. Skipping
      breakfast and spending more than 3 h in front of a screen every day were more
      frequently observed in XXL families. With regard to the availability of various
      food products and beverages at home, no significant differences were observed
      between XXL families and the rest of the studied families. CONCLUSIONS: Greek XXL
      families have lower educational status and lower annual income.

PMID- 21729493
TI  - Transcatheter closure in two rare cases of left-to-right shunt with Cardio-O-Fix
      occluders.
AB  - We present two procedures of transcatheter closure: that of an aorto-pulmonary
      window in a 12-month-old infant with a body weight of 7 kilograms, and that of
      ruptured sinus of Valsalva aneurysm into the right atrium in an adult patient. In
      the first case, we applied the muscular ventricular septal defect Cardio-O-Fix,
      while in the other we applied the patent ductus arteriosus Cardio-O-Fix occluder.
      The procedures were successful in both patients, and we achieved complete closure
      of the unwanted shunts.

PMID- 21729494
TI  - Design and rationale of a genetic cohort study on congenital cardiac disease:
      experiences from a multi-institutional platform in Quebec.
AB  - BACKGROUND: Congenital cardiac disease is the most common malformation, and a
      substantial source of mortality and morbidity in children and young adults. A
      role for genetic factors is recognised for these malformations, but overall few
      predisposing loci have been identified. Here we report the rationale, design, and
      first results of a multi-institutional congenital cardiac disease cohort,
      assembled mainly from the French-Canadian population of the province of Quebec
      and centred on families with multiple affected members afflicted by cardiac
      malformations. METHODS: Families were recruited into the study, phenotyped and
      sampled for DNA in cardiology clinics over the first 3 years of enrolment. We
      performed segregation analysis and linkage simulations in the subgroup of
      families with left ventricular outflow tract obstruction (LVOTO). RESULTS: A
      total of 1603 participants from 300 families were recruited, with 169 out of 300
      (56.3%) families having more than one affected member. For the LVOTO group, we
      estimate heritability to be 0.46-0.52 in our cohort. Simulation analysis
      demonstrated sufficient power to carry out linkage analyses, with an expected
      mean log-of-odds (LOD) score of 3.8 in 67 pedigrees with LVOTO. CONCLUSION: We
      show feasibility and usefulness of a population-based biobank for genetic
      investigations into the causes of congenital cardiac disease. Heritability of
      LVOTO is high and could be accounted for by multiple loci. This platform is
      ideally suited for multiple analysis approaches, including linkage analysis and
      novel gene sequencing approaches, and will allow to establish segregation of risk
      alleles at family and population levels.

PMID- 21729495
TI  - New York Heart Association class assessment by cardiologists and outpatients with
      congenital cardiac disease: a head-to-head comparison of three patient-based
      versions.
AB  - BACKGROUND: The objective of this study was to compare three patient-based New
      York Heart Association assessments with cardiologist assessments in outpatients
      with congenital cardiac disease. METHODS: Consecutive adult outpatients completed
      three questionnaires in a random order: a patient-based translation of the New
      York Heart Association classes, a self-constructed questionnaire based on the New
      York Heart Association classes, and the Specific Activity Scale. The treating
      cardiologist assessed the New York Heart Association class on the same day.
      Patient-cardiologist agreement was assessed by calculating percent agreement and
      weighted kappa. We also explored the level of agreement for patients without co
      morbidity. RESULTS: In all, 86 adults--with a median age of 35.8 years--including
      46 women participated. An agreement of 75.6% (weighted kappa is 0.43; probability
      is smaller than 0.01), 70.6% (weighted kappa is 0.44; probability is smaller than
      0.01), and 74.4% (weighted kappa is 0.28; probability is smaller than 0.01) was
      found between the cardiologist assessment and the patient-based translation, self
      constructed questionnaire, and the Specific Activity Scale, respectively. The
      patient-based translation equally over- and underestimated the New York Heart
      Association class, whereas the self-constructed questionnaire overestimated and
      the Specific Activity Scale underestimated the New York Heart Association class.
      Agreement levels for patients without co-morbidity were higher than agreement
      levels for the total group. CONCLUSION: The patient-based translation yielded
      adequate agreement with cardiologist-assessed New York Heart Association class,
      showed equal over- and underestimation, and was easy to complete. The patient
      based translation with the instruction to only consider functional impairments
      caused by the congenital cardiac defect is recommended in future studies of
      outpatients with congenital cardiac disease.

PMID- 21729496
TI  - Oral feeding outcomes in neonates with congenital cardiac disease undergoing
      cardiac surgery.
AB  - BACKGROUND: Achievement of adequate oral nutrition is a challenging task after
      early neonatal cardiac surgery. This study aims to describe predictors of oral
      feeding outcomes for neonates after early surgical interventions. MATERIALS AND
      METHODS: A retrospective review of neonates admitted with congenital cardiac
      disease over a period of 1 year. We analysed predictors of the need for a feeding
      tube at discharge and the amount taken at each feeding. Multilevel modelling was
      used to look at individual change over time predicting oral amount at each
      feeding. RESULTS: We identified 56 neonates. Diagnoses were heterogeneous; 23% of
      the infants had associated genetic syndromes and 45% required pre-operative
      mechanical ventilation. The median time from birth to surgery was 8.4 days, with
      29 infants fed orally before surgery. The mean time from surgery to first oral
      feeding attempt was 12 hours. Time from surgery to oral feeding, the amount taken
      with first feeding, and cross-clamp times were significant predictors of oral
      feeding success, whereas the presence of a comorbidity--genetic abnormality--and
      longer ventilator dependency predicted failure. Almost half of the neonates
      required a feeding tube upon discharge, and no infant discharged was solely
      breastfed. Discharge with a feeding tube was associated with greater weight gain
      at that time. CONCLUSIONS: Neonates with congenital cardiac disease face
      significant barriers to successfully achieving oral feeding on hospital
      discharge. Enteral feeding guidelines focus on physiological stabilisation and do
      not always address the developmental milestones necessary to support oral
      feeding. Future prospective studies are necessary to identify multimodal
      strategies to optimise early feeding.

PMID- 21729497
TI  - Modified Nikaidoh procedure in a patient with transposition of the great
      arteries, ventricular septal defect, and left ventricular outflow tract
      obstruction with unusual coronary anatomy.
AB  - The Rastelli operation has been the most common procedure for the repair of
      transposition of the great arteries with ventricular septal defect and left
      ventricular outflow tract obstruction. A relatively recent approach is the
      Nikaidoh procedure. Despite the fact that it seems promising, the operation lacks
      long-term follow-up data. It has been postulated that patients with anomalous
      coronary arteries are high-risk candidates for the Nikaidoh procedure and its
      modifications. In this report, we present the case of a patient with
      transposition of the great arteries with remote restrictive ventricular septal
      defect and left ventricular outflow tract obstruction with coronary anomaly -
      with the right coronary artery originating from the left anterior descending
      coronary artery and crossing the right ventricular outflow tract - who underwent
      successful modified Nikaidoh operation.

PMID- 21729498
TI  - Atrial septal defect repair by inversion of a juxtaposed left atrial appendage.
AB  - A 7-year-old child was noted to have dextrojuxtaposition of the left atrial
      appendage at the time of surgical atrial septal defect repair. Given the
      favourable anatomic location and size of the atrial appendage, it was inverted
      and used to close the atrial defect. This is the first report of atrial septal
      defect repair using a juxtaposed atrial appendage. The cardiac anatomy and
      theoretical benefits of this repair are discussed.

PMID- 21729499
TI  - Successful surgical excision of a large left ventricular fibroma in a child.
AB  - Primary cardiac tumours in children are rare. Despite the majority of these
      tumours being benign, they may cause blood flow obstruction, ventricular
      dysfunction, and life-threatening arrhythmias. We present a case of a 4-year-old
      boy with repeated presyncope episodes in whom we found a large left ventricular
      fibroma. Our case emphasises that surgical resection is safely feasible even with
      large fibromas, avoiding cardiac transplantation in childhood.

PMID- 21729500
TI  - Accidental intra-arterial injection of adenosine in a patient with
      supraventricular tachycardia.

PMID- 21729501
TI  - Right bundle branch block as a marker for interatrial septal abnormalities.
AB  - BACKGROUND: Interatrial septal anomalies, which include atrial septal defect,
      patent foramen ovale, and atrial septal aneurysm, are common disorders among
      adult patients. Early detection of interatrial septal anomalies is important in
      order to prevent haemodynamic consequences and/or thromboembolic events.
      Electrocardiogram offers some clues that should serve as hints for detection of
      interatrial abnormalities. The aim of our study was to analyse the interatrial
      septum by transoesophageal echocardiography in patients with electrocardiogram
      signs of right bundle branch block and in those without right bundle branch
      block. METHODS AND RESULTS: In a prospective study, 87 adult patients were
      included, that is, 41 with electrocardiogram signs of right bundle branch block
      forming the first group and 46 without right bundle branch block forming the
      second group. Interatrial septal anomalies were present in 80.5% of the patients
      with right bundle branch block, with patent foramen ovale (39.02%) being the most
      prevalent disorder, followed by atrial septal aneurysm (21.9%) and atrial septal
      defect (19.5%). Interatrial septal abnormalities were significantly more frequent
      in the first group compared with the second group (80.5% versus 6.5%, p value
      less than 0.001). Independently, patent foramen ovale was significantly more
      prevalent in patients with right bundle branch block (39.02% versus 4.3%, p value
      less than 0.001), as were atrial septal aneurysm (21.9% versus 2.2%, p value
      equal 0.01) and atrial septal defect (19.5% versus 0%, p value equal 0.004).
      CONCLUSIONS: Right bundle branch block should serve as a valuable indicator to
      motivate a detailed search for interatrial septal abnormalities.

PMID- 21729502
TI  - Systemic arterial supply of the right lung with venous drainage to the pulmonary
      arterial circuit.
AB  - In a girl suffering from "Scimitar syndrome", a rerouting of the scimitar vein
      was performed at the age of 6 years, but no embolisation of the aberrant systemic
      vessel was done. She presented with recurring respiratory problems 13 years
      later. An angiography revealed an invert flow from the aberrant systemic vessel
      via the right pulmonary artery into the left pulmonary artery. After
      pneumonectomy, she recovered well.

PMID- 21729503
TI  - Subtype of pulmonary artery sling with ventricular septal defect.

PMID- 21729504
TI  - Objectively assessed physical activity and sedentary behaviour does not differ
      between children and adolescents with and without a congenital heart defect: a
      pilot examination.
AB  - OBJECTIVES: To objectively evaluate and describe physical activity levels in
      children with a stable congenital heart defect and compare those levels with
      children who do not have a congenital heart defect. METHODS: We matched 21 pairs
      of children for gender and grade in school and gave them an accelerometer-based
      motion sensor to wear for 7 consecutive days. RESULTS: Physical activity levels
      did not differ between children with and without a congenital heart defect.
      During the 7 days of monitoring, children in this study spent most of their time
      in sedentary behaviours, that is, 6.7 hours of the 13 monitored hours, 54 minutes
      in moderate-intensity physical activity, and 12 minutes in vigorous-intensity
      physical activity. Less than one-fifth of all participants, with or without a
      congenital heart defect, accumulated sufficient physical activity to meet current
      physical activity recommendations for children and adolescents. CONCLUSION:
      Children with a stable congenital heart defect have activity behaviours that are
      similar to children without a congenital heart defect. Habitual physical activity
      in children with a congenital heart defect should be encouraged early on in life
      to develop strong physical activity habits that will hopefully follow them across
      their lifespan.

PMID- 21729505
TI  - Symptomatic myocardial bridges in children: a case report with review of
      literature.
AB  - Myocardial bridge is a rare congenital coronary anomaly in children, usually seen
      in the setting of hypertrophic cardiomyopathy and in left ventricular
      hypertrophy. Most myocardial bridges are believed to represent a benign
      anatomical variant; however, symptomatic myocardial bridge is a distinct subgroup
      of pathological variant, linked to myocardial ischaemia, ventricular arrhythmia,
      and sudden cardiac death. We present a case of a symptomatic myocardial bridge in
      a 5-year-old boy with mild hypertrophic cardiomyopathy who underwent supra
      arterial myotomy, automatic defibrillator placement, and long-term Beta-blocker
      therapy. We also present 10 years of follow-up with a review of literature
      regarding symptomatic myocardial bridges in the paediatric age group.

PMID- 21729506
TI  - Linguistic validation of a disease-specific quality of life measure for children
      and teenagers with cardiac disease.
AB  - INTRODUCTION: To anglicise an American--that is, English language--disease
      specific health-related quality of life measure, using the Paediatric Cardiac
      Quality of Life Inventory, for children in the age group of 8-12 years and
      adolescents in the age group of 13-18 years with cardiac disease, and to assess
      conceptual equivalence of the American and British versions. METHODS: A process
      of forward and backward translation of the measure was undertaken before focus
      groups and individual interviews with 40 participants--that is, 20
      children/adolescents with cardiac disease and 20 parents of children/adolescents
      with cardiac disease--to determine their understanding of the meaning of the
      questions. RESULTS: Interviews established that participants understood the
      meaning of the questions, although some found it difficult to explain the meaning
      of questions in which the language was explicit and wanted instead to answer the
      individual questions as they applied to them/their child. There was agreement
      that all versions of the questionnaire were relevant and comprehensive, and that
      the length of the questionnaires was acceptable and practical. CONCLUSIONS: The
      anglicised version of the Paediatric Cardiac Quality of Life Inventory appears to
      be a linguistically valid measure of health-related quality of life for children
      and adolescents with cardiac disease. The psychometric properties of the
      anglicised Paediatric Cardiac Quality of Life Inventory are now being tested in a
      multi-centre study in the United Kingdom.

PMID- 21729507
TI  - Aortic mineralisation in children with congenital cardiac disease.
AB  - BACKGROUND: Congenital cardiac diseases are the most frequent congenital
      malformations. In adult patients, the mineralisation of the aorta due to
      cardiovascular disease is very common, but vascular mineralisation in paediatric
      cardiopathies is a topic less studied. This study shows that children with a
      complex congenital cardiopathy show a high degree of vascular mineralisation in
      the ascending aorta. This can be part of the cardiac failure pathophysiology due
      to congenital cardiopathies. OBJECTIVE: The aim of this study was to determine
      the presence and degree of vascular mineralisation in samples of the ascending
      and descending aorta of children with complex congenital cardiopathies. DESIGN:
      We conducted a cross-sectional study. SUBJECTS: We obtained 34 vascular tissues
      from the autopsies of 17 children with congenital cardiac disease. METHODS: We
      used a scanning electron microscope with an energy-dispersive X-ray spectroscopy
      in order to analyse the vascular tissues. RESULTS: The amount of minerals was two
      times higher in the ascending aorta than in the descending aorta of children with
      congenital cardiac disease. CONCLUSIONS: The study provides evidence that
      vascular mineralisation can start at an early age, and that it is higher in the
      ascending aorta than in the descending aorta.

PMID- 21729508
TI  - Comparative efficacy of sildenafil in Eisenmenger's syndrome secondary to atrial
      septal defect versus ventricular septal defect: a cardiac catheterisation follow
      up study.
AB  - OBJECTIVES: This study evaluates the efficacy and safety of sildenafil in
      patients with Eisenmenger's syndrome with special emphasis on haemodynamic
      parameters and its comparative efficacy in atrial septal defect versus
      ventricular septal defect patients. METHODS: Oral sildenafil was given to 22
      patients with Eisenmenger's syndrome - eight with atrial septal defect and 14
      with ventricular septal defect - after detailed baseline evaluation including a
      six-minute walk test, echocardiography, and cardiac catheterisation. Patients
      were followed up for a period of 6 months for functional class assessment and six
      minute walk distance. Cardiac catheterisation was repeated in all patients.
      RESULTS: A significant improvement in the World Health Organization functional
      class, six-minute walk distance, mean pulmonary arterial pressure, and pulmonary
      vascular resistance was noticed. Systemic arterial and mixed venous oxygen
      saturations were also significantly improved along with improvement in pulmonary
      blood flow. None showed any significant side effects or worsening of systemic
      arterial saturation. At baseline, mean pulmonary arterial pressure, pulmonary
      vascular resistance, and pulmonary/systemic vascular resistance ratios were
      significantly higher in ventricular septal defect patients than in atrial septal
      defect patients. Atrial septal defect patients showed better response in clinical
      as well as haemodynamic parameters. CONCLUSIONS: Sildenafil is an effective and
      safe agent for patients with Eisenmenger's syndrome. It improves their functional
      capacity as well as haemodynamic parameters. The beneficial effects are greater
      in patients with Eisenmenger's syndrome secondary to atrial septal defect than
      ventricular septal defect.

PMID- 21729509
TI  - Quality of life of patients with congenital heart diseases.
AB  - OBJECTIVES: To assess the perception of the quality of life of adolescents and
      young adults with congenital heart disease and to examine the variables that have
      a negative impact on it and that add a resilience effect. METHODS: A total of 22
      male and 18 female patients, aged 12-26 years, of whom 27 were admitted to
      surgery and 13 were not, participated in this study. All patients had complete
      medical records and were interviewed once; demographic and clinical data were
      collected, and patients filled a questionnaire on quality of life, the WHOQOL
      BREF, and underwent an interview on social support, educational style, self
      image, functional limitations, and emotional adjustment. RESULTS/CONCLUSIONS: Our
      patients showed a better perception of quality of life than did the general
      population, on the basis of psychological, social relationship and environment
      scales. Older patients hold a better perception of quality of life on the
      psychological scale. Cyanosis did not show any significant impact over perception
      of quality of life decay; however, the number of surgical procedures and the
      persistence of moderate-to-severe residual injuries had considerable detrimental
      effect. Social support had an impact on increasing resilience, promoting
      adjustment to illness. Several factors may play a role in adjustment to
      congenital heart disease, either improving the perception of quality of life or
      worsening it. We may conclude that some buffer variables on congenital heart
      disease may play roles in increasing the perception of quality of life of
      patients during their lifetime, social support probably explaining why the
      perception of quality of life is better than in the normal population. The number
      of surgeries and the moderate-to-severe residual injuries, however, reverted that
      effect.

PMID- 21729510
TI  - Critical coarctation in an extremely low birth weight pre-term infant.
AB  - Neonatal interventions for critical aortic coarctation may be associated with
      considerable morbidity and mortality if the patient is extremely premature. We
      report the successful treatment of critical coarctation in a 25-week, 740-gram
      infant using initial clipping of the duct until continued prostaglandin E1
      infusion delayed end-to-end anastomosis 7 weeks later.

PMID- 21729511
TI  - Congenital giant aneurysm of the left atrial appendage in an infant.
AB  - Aneurysm of the left atrial appendage is a rare pathological condition. We
      describe the diagnostic work-up and surgical management of a child with giant
      congenital aneurysm of the left atrial appendage.

PMID- 21729512
TI  - Geography or pathology? Regional variation in atrial septal defect closure rates
      and techniques.
AB  - BACKGROUND: Since the introduction of percutaneous closure in the United States,
      rates of secundum atrial septal defect and patent foramen ovale closures have
      increased substantially. Whether or not closure rates are uniform or vary due to
      differences in regional practice patterns is unknown. We sought to investigate
      this by comparing regional rates of closure across Florida. METHODS: We
      identified all atrial septal defect closures from 2001 to 2006 in the Florida
      State Inpatient Database. Using small area analysis, zip codes were assigned to
      Hospital Referral Regions based on where patients were most likely to go for
      closure. We obtained population-normalised rates of overall, percutaneous, and
      surgical closure. RESULTS: Of 1830 atrial septal defect and patent foramen ovale
      closures from 2001 to 2006, 751 were surgical and 1004 were percutaneous. The
      statewide closure rate was 1.91 per 100,000 people per year; regional rates
      varied 3.8-fold from 0.78 to 2.94 per 100,000 people per year. Percutaneous rates
      varied sevenfold from 0.25 to 1.75 per 100,000 people per year, while surgical
      rates varied 2.71-fold from 0.53 to 1.44 per 100,000 people per year.
      CONCLUSIONS: Despite a consistent prevalence of atrial septal defects, and patent
      foramens ovale, rates of repair vary across regions, suggesting that closure is
      driven by provider practice patterns rather than patient pathology. Efforts
      should be directed towards increasing consensus regarding the appropriate,
      evidence-based indications for closure so as to avoid the costs and potential
      negative sequelae of over- or undertreatment.

PMID- 21729513
TI  - Lessons from inter-stage cardiac magnetic resonance imaging in predicting
      survival for patients with hypoplastic left heart syndrome.
AB  - This study describes single-unit experience and explores risk stratification,
      with protocolised inter-stage cardiac magnetic resonance imaging for infants with
      hypoplastic left heart syndrome. Survival was retrospectively analysed among the
      cohort of locally followed survivors of Norwood Stage I procedure, who underwent
      magnetic resonance imaging under general anaesthesia from 2003 to 2008. This
      included 32 patients: 17 with Sano conduit and 15 with arterio-pulmonary shunt.
      The median (inter-quartile range) age and weight at scan were 3.1 (2.6-4.6)
      months and 5.0 (4.5-5.3) kilograms, respectively. Using morphologic definitions,
      the median coarctation index was 0.71 (0.57-0.83). The degree of proximal right
      and left pulmonary artery narrowing was 25% (14-44%) and 25% (11-50%),
      respectively. The median right ventricular ejection fraction was 54% (48-59%).
      The ejection fraction was not related to the coarctation index or to pulmonary
      artery narrowing. Patients were followed up for a median of 19.2 (10.8-46.0)
      months, during which 13 (41%) had an intervention in addition to routine Norwood
      Stage II surgery and seven died. Risk of death was related to reduced right
      ventricular ejection fraction, with a hazard ratio of 0.91 (95% confidence
      interval 0.85-0.98, p = 0.02), and the cumulative number of focal stenoses of neo
      aortic arch and pulmonary arteries (hazard ratio 2.71, 95% confidence interval
      1.14-6.44, p = 0.02). CONCLUSIONS: In addition to comprehensive three-dimensional
      morphologic imaging, inter-stage cardiac magnetic resonance imaging provides a
      ventricular functional index that may predict outcome in patients with
      hypoplastic left heart syndrome. Measures to preserve right ventricular systolic
      function and relieve stenoses are paramount within the complex management
      strategies for these patients.

PMID- 21729514
TI  - Atypically located cardiac haemangioma of the mitral valve.
AB  - We report an adolescent with a benign cardiac haemangioma with attachments
      exclusively to the anterior leaflet of the mitral valve. On the basis of our
      review of the literature, this study has not been reported previously.

PMID- 21729515
TI  - Adult congenital cardiac surgery in Indonesia.
AB  - BACKGROUND: Successful paediatric cardiac surgery and cardiology treatment has
      resulted in an increase in the use of surgery as a method of treatment of
      congenital cardiac disease in adult population. However, late detection and lower
      socio-economic condition in developing countries might change patients'
      characteristics by the time they come for treatment. This study aimed to
      elaborate the long-term surgical results of adult congenital cardiac disease in
      Indonesia as a developing country. METHODS AND RESULTS: We reviewed
      retrospectively all adult congenital cardiac disease patients with a mean age of
      28 years plus or minus 9.5 years, who underwent surgery at National
      Cardiovascular Center. The types of procedures used were corrective in 338
      patients (89.2%), palliative in 10 patients (2.6%), and re-operations in 31
      patients (8.2%). The overall hospital mortality rate was 2.6% but as high as 20%
      with palliative surgery. Post-operative New York Heart Association class III-IV
      is the only independent predictor of death at 60 months (hazard ratio 61.48, 95%
      confidence interval 9.41-401.69, p<0.001). The survival rates were 96.3% and 95%
      for overall and non-atrial septal defect in patients at 60 months, which was
      highest in corrective procedures (97.6%). The percentage of patients free of re
      operation at 5 years' follow-up was 85.4% and 42.7% at 10 years. CONCLUSION: In
      developing countries, surgical treatment of adult congenital cardiac disease is
      effective and safe, with an overall survival rate of 96.3% at 60 months. Due to
      high mortality rate, palliative surgery of a non-atrial septal defect patient is
      recommended to be discontinued. The independent predictor of mortality was post
      operative New York Heart Association functional class III-IV.

PMID- 21729516
TI  - Silent rupture of sinus of Valsalva aneurysm: a refutation of the Okham's razor
      principle.
AB  - Aneurysm of the sinus of Valsalva is an uncommon congenital lesion rarely
      reported in children. Unruptured aneurysms commonly go undiagnosed until a
      rupture has occurred. Usually, ruptured sinus of Valsalva presents with cardiac
      failure. There may be a history of trauma or infective endocarditis preceding the
      rupture. Asymptomatic paediatric presentation of ruptured sinus of Valsalva is
      rare. We discuss the cases of two children who presented with a murmur and were
      diagnosed with ruptured sinus of Valsalva. This unusual presentation in children
      highlights the importance of careful routine physical examinations and the
      evaluation of new murmurs. The Okham's razor principle states that "when you hear
      hoofbeats - think horses not zebras". Sometimes, it is important to think beyond
      the usual in medicine, to avoid missing lesions that, if left untreated, could
      lead to adverse outcomes.

PMID- 21729517
TI  - Veno-venous bridges: the forerunners of the sinus venosus defect.
AB  - BACKGROUND: Differentiation of the so-called sinus venosus defect from other
      defects permitting shunting between the atrial chambers remains problematic. The
      lesion is not a true septal defect, and current theories to explain the existence
      of the sinus venosus defect fall short. The presence of persistent systemic to
      pulmonary venous connections has been proposed to explain the existence of the
      sinus venosus defect. METHODS: Clinical histories and radiological findings of
      six patients are reviewed. Three patients have veno-venous bridges, two have
      partial anomalous pulmonary venous connections, and one patient has a sinus
      venosus defect. The clinical information is reviewed, along with current
      developmental and morphological considerations. DISCUSSION: We provide
      radiographic, developmental, and morphological evidence to support the theory
      that a so-called sinus venosus defect is the consequence of persistence of foetal
      systemic to pulmonary veno-venous bridges, rather than of deficiencies in atrial
      septation.

PMID- 21729518
TI  - Can RoTEM(r) analysis be applied for haemostatic monitoring in paediatric
      congenital heart surgery?
AB  - BACKGROUND: Successful management of bleeding disorders after congenital heart
      surgery requires detection of specific coagulation disturbances. Whole-blood
      rotation thromboelastometry (RoTEM(r)) provides continuous qualitative
      haemostatic profiles, and the technique has shown promising results in adult
      cardiac surgery. SETTING: To compare the performance of RoTEM(r) with that of
      conventional coagulation tests in children, we conducted a descriptive study in
      children undergoing congenital cardiac surgery. For that purpose, 60 children
      were enrolled and had blood samples taken before, immediately after, and 1 day
      after surgery. Conventional coagulation tests included: activated partial
      thromboplastin time, prothrombin time, fibrinogen, fibrin D-dimer, thrombin
      clotting time, factor XIII, and platelet count. RESULTS: Post-surgical
      haemostatic impairment was present to some degree in all children, as seen by
      pronounced changes in activated partial thromboplastin time, prothrombin time,
      thrombin clotting time, and platelet count, as well as RoTEM(r) analysis.
      RoTEM(r) showed marked changes in clotting time - prolonged by 7-18% - clot
      formation time - prolonged by 46-71% - maximum clot firmness - reduced by 10-19%,
      and maximum velocity - reduced by 29-39%. Comparison of the two techniques showed
      that conventional coagulation tests and RoTEM(r) performed equally well with
      regard to negative predictive values for excessive post-operative drain
      production - more than 20 millilitres per kilogram per 24 hours after surgery -
      with an area under the curve of approximately 0.65. CONCLUSION: RoTEM(r) can
      detect haemostatic impairments in children undergoing cardiac surgery and the
      method should be considered as a supplement in the perioperative care of the
      children where targeted transfusion therapy is necessary to avoid volume
      overload.

PMID- 21729519
TI  - One train may hide another: anomalous origin of the left coronary artery from the
      pulmonary artery revealed by supraventricular tachycardia.
AB  - We report the case of a 1-month-old boy with an unusual association of
      supraventricular tachycardia and anomalous origin of the left coronary artery
      from the pulmonary artery. Although signs of infarction were visible on the first
      electrocardiogram, the presence of an arrhythmia did not immediately suggest a
      coronary anomaly. Echocardiography allowed the diagnosis, thus leading to
      appropriate care.

PMID- 21729520
TI  - Role of toxicological determinations of amphetamines and cannabinoids in hair of
      adolescent patients in cardiologic diagnostic management.
AB  - BACKGROUND: Parental suspicions that the child may possibly take narcotics may be
      substantiated by hair analysis, which may not only identify the narcotic abuse
      profile, but also define the minimum period of narcotic usage. OBJECTIVE: A
      toxicological hair analysis aiming at detecting the presence of amphetamines and
      cannabinoids in children with cardiac complaints of unclear aetiology, with a
      view of establishing a diagnosis. MATERIAL AND METHOD: The authors analysed hair
      samples collected from the occipital region of three adolescent patients for the
      presence of substances of abuse--amphetamines and cannabinoids. Hair strands were
      subjected to segmentation and chemical processing and subsequently analysed by
      liquid chromatography-mass detection method. RESULTS: Indicating the presence of
      amphetamines and cannabinoids in hair samples, the toxicological analysis allowed
      for explaining cardiac complaints and personality changes in adolescent patients,
      with the said changes being associated with addiction to the above xenobiotics
      extending over some period.

PMID- 21729521
TI  - [Mechanism of leukemia relapse: novel insights on old problem].
AB  - Relapse, which puzzled several generations of hematologists, is the bottle-neck
      of radical treatment for leukemias. The progress of Human Microbiome Project at
      the beginning of 21st century suggested that human body was a super-organism
      constituted by the core of human cells and symbiotic microorganisms. The
      elucidation and characterization of endogenous retrovirus and prion protein
      suggested the possible effects of co-evolutional microorganisms on human health.
      Recently, the elucidation of the roles of tunneling nanotubes in intercellular
      communication and transportation suggested a novel way for cellular communication
      and transport of oncogenic materials. The role and significance of in vivo cell
      fusion have been studied in more detail. On the other hand, donor cell leukemia
      was reported. All of these approaches provide novel insights for studying the
      mechanism of leukemia relapse. Based on previous work, the authors suggest the
      hypothesis: there are two possible mechanisms for the relapse of leukemias: the
      minimal residual disease (MRD) and intercellular transportation of oncogenic
      materials.

PMID- 21729522
TI  - [Screening and structure analysis of nucleic acid aptamers binding to surface of
      CD33(+)/CD34(+) cells from patients with acute myeloid leukemia subtype M2].
AB  - A little is known about the specific marker on the surface of acute leukemia
      cells, leading to the lack of the specific diagnosis method for acute leukemia.
      Therefore, in this study, cell-systematic evolution of ligands by exponential
      enrichment (cSELEX) was performed to screen the aptamers binding to
      CD33(+)/CD34(+) cells from the patients with acute myeloblastic leukemia (AML) of
      M(2) subtype (AML-M2) so as to provide the basis for finding the specific marker
      on the surface of AML-M(2) CD33(+)/CD34(+) cells. Firstly, AML-M2 CD33(+)/CD34(+)
      cells were sorted and used as targeted cells, and normal CD33(+)/CD34(+)cells
      were used as counter-targeted cells; the aptamers binding to CD33(+)/CD34(+)
      cells from patients with AML-M2 were screened from the single strand
      deoxyribonucleic acid (ssDNA) library by cSELEX. Subsequently, each aptamer
      structure was analyzed after cloning and sequencing. The results indicated that
      after 13 round of screenings, the enrichment of aptamers in the ssDNA library was
      ranged from 0.7% to 52.9%, and reached steady state at 13th round screening.
      Sequence analysis for 30 aptamers showed that most of the aptamers born one of
      the three conserved sequences of CCCCT, CTCTC, and CTCAC. Secondary structure
      analysis indicated that three different secondary structures existed in these
      aptamers. It is concluded that the aptamers binding to the AML-M(2)
      CD33(+)/CD34(+) cells are successfully screened, which lay the basis for further
      looking for the specific marker on the surface of AML-M2 CD33(+)/CD34(+) cells,
      and the molecular diagnosis of the AML-M2 leukemia.

PMID- 21729523
TI  - [Expression of ADAR1 isoforms in murine acute T-ALL leukemia model].
AB  - This study was purposed to investigate the expression of ADAR1 isoforms of P110
      and P150 during the development of murine leukemia. A Notch1 over-expressing
      murine T cell acute lymphoblastic leukemia model was used to study the expression
      of ADAR1. BMMNC were isolated at different stages of disease and CD45.2(+)GFP(+)
      leukemia cells were sorted by flow cytometry at late stage. The expression of
      ADAR1 was detected by real time quantitative PCR. The results showed that mouse
      bone marrow cells from both leukemia and control groups expressed P110 and P150.
      Difference of P110 and P150 mRNA expression were observed during the development
      of leukemia. The expression of P110 dramatically increased and was significantly
      higher than that in control group. However, the expression level of P150 in
      leukemia group decreased stably and reached one-fourth of that in control group
      at 14 day. Furthermore, similar expression patterns could be detected in sorted
      CD45.2(+)GFP(+) leukemia cells. It is concluded that the mRNA expressions of P110
      and P150 show diverse patterns in the development of leukemia, suggesting that
      RNA editing mediated by ADAR1 isoforms may play different roles in leukemia.

PMID- 21729524
TI  - [Expression of CIAPIN1 gene in BMMNC of patients with leukemia].
AB  - This study was aimed to investigate the expression level of CIAPIN1 mRNA in
      leukemia patients and explore its significance in leukemias. The fresh bone
      marrow was collected from 112 newly diagnosed leukemia patients, the total RNA
      was extracted by means of TRIzoL, the cDNA was synthesized, the expression of
      CIAPIN1 mRNA was detected by real-time quantitative PCR using beta-actin as
      internal reference; 10 normal healthy persons were selected as controls. The
      results showed that the expression of CIAPIN1 mRNA was statistically higher in
      acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and chronic phase
      chronic myeloid leukemia (CML) patients than that in normal persons (p < 0.05);
      but there was no statistical difference between chronic lymphocytic leukemia
      (CLL) and normal persons (p > 0.05). It is concluded that the CIAPIN1 gene higher
      expresses in MNC of newly diagnosed leukemia patients, up-regulation of CIAPIN1
      expression may play an important role in pathogenesis of leukemia.

PMID- 21729525
TI  - [Construction of lentiviral vector carrying human VE-cadherin gene and expression
      of VE-cadherin in leukemic cell line Sup-B15].
AB  - In order to construct a lentiviral vector carrying human VE-cadherin gene, and to
      express VE-cadherin in Sup-B15 cells, the VE-cadherin gene was amplified by RT
      PCR from the human placenta, and then cloned into pCR-Blunt vector. The VE
      cadherin DNA fragment was subcloned into pLB vector to generate a lentiviral
      vector pLB-VEC. Recombinant lentivirus was generated by co-transfection of three
      plasmids into 293FT packing cells using lipofectamine 2000. The Sup-B15 cells
      were transfected by the lentivirus. The post-transfected Sup-B15 cells were
      observed by microscopy and flow cytometry. Western blot was used to determine the
      expression of VE-cadherin. The results showed that the VE-cadherin DNA fragment
      was amplified from human placenta and was cloned into pCR-Blunt vector, the
      recombinant lentiviral vector pLB-VEC was successfully constructed. High titer
      lentivirus was prepared by 3-plasmid packing system, and transfected into Sup-B15
      cells in vitro effectively. The obviously morphological changes occurred in
      transfected cells, the expression of VE-cadherin protein could be detected in Sup
      B15 cells via flow cytometry and Western blot. It is concluded that the
      lentiviral vector pLB-VEC carrying human VE-cadherin gene is successfully
      constructed; VE-cadherin gene is expressed in Sup-B15 cells via lentiviral vector
      transfection, which provides an optional tool for further study on the mechanism
      of VE-cadherin controlling leukemia development.

PMID- 21729526
TI  - Expressions of cell cycle associated factors geminin and cdt1 in patients with
      acute leukemia.
AB  - The purpose of this study was to detect the expression levels of geminin and cdt1
      in peripheral blood and bone marrow from patients with newly diagnosed acute
      leukemia (AL), and further explore effects of them in the pathogenesis of AL.
      mRNA expression of geminin and cdt1 in peripheral blood and bone marrow of newly
      diagnosed AL patients was detected by SYBR Green real-time quantitative reverse
      transcription polymerase chain reaction(SYBR-RT-PCR). The results showed that
      mRNA expressions of both geminin and cdt1 in peripheral blood were positive in 10
      out of 13 newly diagnosed ALL patients (76.92%) and in 9 out of 14 newly
      diagnosed AML patients (64.29%), while no positive expression of these 2 genes
      was detected in 10 normal controls; mRNA expression levels of geminin and cdt1 in
      bone marrow of newly diagnosed ALL and AML patients were 108.06 +/- 67.34 and
      52.37 +/- 35.16, 62.66 +/- 58.69 and 26.68 +/- 22.29, respectively, which were
      higher than those in normal controls (11.81 +/- 2.83 and 7.32 +/- 5.77), there
      were significant differences (p < 0.01 and p < 0.05). mRNA expression of geminin
      was significantly positive related to mRNA expression of cdt1 in bone marrow of
      34 newly diagnosed AL patients (r = 0.55, p < 0.01). It is concluded that mRNA
      expressions of geminin and cdt1 are enhanced and significantly positively related
      between them in bone marrow of AL patients. The over-expression of geminin and
      cdt1 mRNA may play an important role in pathogenesis of AL.

PMID- 21729527
TI  - [ID4 promoter methylation in acute myeloid leukemia].
AB  - Objective of this study was to investigate the ID4 gene methylation status in
      patients with acute myeloid leukemia (AML). Methylation-specific PCR (MS-PCR) was
      used to detect the promoter methylation status of ID4 gene in bone marrow samples
      from 46 AML patients with different subtypes and stage of disease and from 10
      patients with iron deficiency anemia (IDA) as a control. The results showed that
      ID4 gene in bone marrow of IDA patients was completely non-methylated, while ID4
      gene methylation was found in 39 out of 46 AML patients (positive rate 84.8%).
      The positive rates of ID4 gene methylation in different FAB types M1, M2, M3, M4,
      M5, M6 were 100% (4/4), 75% (9/12), 100% (8/8), 77.8% (7/9), 81.8% (9/11), 100%
      (2/2) respectively. The positive rates of ID4 gene methylation in newly diagnosed
      and complete remitted of AML patients were 90% (27/30) and 63.3% (7/11)
      respectively; ID4 methylation was detected in 5 relapsed and refractory AML
      patients. There were statistically significant differences in ID4 gene
      methylation between AML and IDA patients (p < 0.01). It is concluded that
      compared with IDA patients, ID4 gene methylation changes of different degrees
      occur in AML patients with different subtypes and stages, which suggests that ID4
      gene methylation may be an early molecular event in the process of AML.

PMID- 21729528
TI  - [CD96 expression on bone marrow mononuclear cells in 91 patients with acute
      leukemia].
AB  - This study was aimed to investigate the expression of CD96 on bone marrow
      mononuclear cells (BMMNC) from 91 patients with acute leukemia, and the results
      were analyzed with clinical pathological data. Flow cytometry was used to detect
      CD96 molecule on the bone marrow mononuclear cell surface of 91 newly diagnosed
      patients with acute leukemia, and 15 healthy adults were served as normal
      controls. The results showed that the average rate of CD96(+) expression on BMMNC
      (CD45(+) CD34(+) CD19(+)) of 21 patients with B-ALL was (17.41 +/- 27.97)%, the
      average rate of CD96(+) expression on stem cells (CD45(+)CD34(+)CD7(+)) of 11
      patients with T-ALL was (46.98 +/- 45.55)%, the average rate of CD96(+)
      expression on BMMNC (CD45(+)CD34(+)CD38(-)) of 59 patients with AML was (16.69 +/
      25.08)%, while the average rate of CD96(+) on BMMNC of healthy adult controls
      was (0.52 +/- 1.84)%, there was significant difference in average rate of CD96(+)
      expression between above-mentioned patients and healthy adult controls (p <
      0.05). Otherwise the average rate of CD96(+) on BMMNC after treatment showed no
      statistical difference between patient group with CR (1.68 +/- 2.31) and healthy
      controls, but demonstrated statistical difference between patients without CR and
      healthy controls (p > 0.05). The leukocyte count, hemoglobin level and platelet
      count in CD96(+) group had no obvious difference from CD96(-) ones (p > 0.05). No
      change found in the field of molecular biology and cytogenetic between these 2
      groups. It is concluded that CD96 expression is different in different types of
      leukemia. The positive expression of CD96 on bone marrow hematopoietic stem cells
      in patients with acute leukemia may be associated with primary drug resistance,
      relapse and progression. The CD96 on BMMNC of acute leukemias can be a helpful
      prognostic indicator in treatment response assessment.

PMID- 21729529
TI  - [Relation of GSTP1 and CYP2E1 polymorphisms with susceptibility to acute
      leukemia].
AB  - This study was aimed to investigate the relation of glutathione S-transferase pI
      (GSTP1) and cytochrome P450 enzyme 2E1 (CYP2E1) gene polymorphisms with the
      susceptibility to acute leukemia (AL) in Chinese population. The GSFP1 and CTP2E1
      gene polymorphisms in 150 patients with AL and 150 patients with non
      hematological diseases or non-tumor as controls were detected by means of case
      control paired 1:1 method and ligase detection reaction (LDR) techniques. The
      results indicated that the frequently of G allele and Ile/Val + Val/Val of GSTP1
      gene (26.7%and 44% respectively) in AL group were higher than those in control
      group (10% and 16% respectively); the AL risk for persons with Ile/Val + Val/Val
      was 3.260-fold (95%CI = 1.527 - 5.236) of persons with Ile/Ile. The further
      stratified analysis showed the frequency of Ile/Val + Val/Val in AML group was
      higher than that in control group (55% vs 16%, p < 0.05); the AML risk for
      persons with Ile/Val + Val/Val was 2.214-fold (95% CI = 1.009-3.260) as persons
      with Ile/Ile. The frequencies of C2 allele (16.7%) and C1C2/C2C2 of CYP2E1 gene
      (30%) in AL group seemed higher than those in control groups (13.9% and 26%), but
      the difference between them was not statistical significant (p > 0.05). The
      further stratified analysis showed that C1C2/C2C2 of CYP2E1 gene occurred more
      frequently in AML group (36%) than that in control group (32%), but there was no
      statistical difference between them (p > 0.05). Combined genotype analysis showed
      that the AML risk for persons in combination of lle/Val + Val/Val of GSTP1 gene
      with C1C2 + C2C2 of CYP2E1 gene increased by 3.208-fold. It is concluded that the
      GSTP1 gene is related with susceptibility to AML, the AL risk for persons with
      lle/Val + Val/Val of GSTP1 gene decreased, while CYP2E1 gene is not related with
      susceptibility to AL, the AML risk for persons in combination of GSTP1 wildtype
      with CYP2E1 hybrid and mutant genotype can be further decreased.

PMID- 21729530
TI  - [Influence of PP2A activator on proliferation of HL-60 cells and analysis of PP2A
      activity changes in patients with acute myeloid leukemia].
AB  - In order to investigate the effect of PP2A activator and PP2A inhibitor on
      proliferation of HL-60 cells and analyze the changes of PP2A activity in patients
      with acute myeloid leukemia (AML), HL-60 cells were treated with FTY720 alone or
      in combination with okadaic acid (OA) for 24 hours in culture. Cell proliferation
      was assayed with CCK8 kit. In addition, 20 AML patients including de novo AML and
      relapsed AML were enrolled in this study. The activity of PP2A in the peripheral
      blood mononuclear cells of patients was assayed with a PP2A Immunoprecipitation
      Phosphatase Assay Kit, the data were analyzed by software SPSS 16.0. The results
      indicated that as compared with control group, the proliferation of cells in
      FTY720 group was obviously inhibited (p < 0.05). The proliferation of cells in
      FTY720 + OA group was slightly inhibited as compared with the control group,
      there was no statistical difference (p > 0.05), but there was significant
      difference between the FTY720 + OA and FTY720 groups (p < 0.05). The activity of
      PP2A in AML patients (453.67 +/- 102.52 pmol phosphate) was obviously lower than
      that in the normal controls (673.29 +/- 96.32 pmol phosphate), there was
      significant difference between them (p < 0.01). It is concluded that the
      activation or inhibition of PP2A can affect the proliferation of HL-60 cells in
      vitro. Compared with healthy individuals, the activity of PP2A in AML patients is
      obviously lower. PP2A protein playing a key role in the occurrence and
      development of AML may be valuable for the diagnosis and treatment of AML.

PMID- 21729531
TI  - [Expression of autophagy related gene Beclin1 and MAPLC3 in bone marrow
      mononuclear cells isolated from acute leukemia patients and its significance].
AB  - This study was purposed to detect the expression of autophagy-related gene
      Beclin1 and microtubule-associated protein 1 light chain 3 (MAPLC3) in bone
      marrow mononuclear cells (BMMNC) isolated from acute leukemia (AL) patients, and
      to explore its significance. Transmission electron microscopy and RT-PCR were
      used to detect the autophagy activity and the expression level of Beclin1 and
      MAPLC3 mRNA in BMMNC isolated from 27 AL patients with de novo, refractory or
      relapse AL and completely remission and 31 normal persons respectively. The
      results showed that autophagy activity and expression levels of Beclin1 and
      MAPLC3 mRNA in BMMNC from de novo AL patients were 80%, 0.68 +/- 0.18, 0.24 +/-
      0.06, respectively; those in BMMNC from refractory or relapse AL patients were
      100%, 0.79 +/- 0.09, 0.30 +/- 0.07, respectively; those in BMMNC from CR patients
      were 40%, 0.52 +/- 0.15, 0.16 +/- 0.04, respectively, while those in BMMNC from
      normal persons were 20%, 0.57 +/- 0.13, 0.16 +/- 0.05, respectively. The
      autophagic activity and expression levels of Beclin1 and MAPLC3 mRNA in de novo
      and refractory or relapse AL patients were higher than those in normal persons,
      with statistical significance (p < 0.05), while the comparison between CR
      patients and normal control showed no statistical difference (p > 0.05). It is
      concluded that autophagy activity and Beclin1 and MAPLC3 mRNA expression level of
      in de novo and refractory or relapse patients are higher than those in normal
      control, and the up-regulation of autophagy activity and expression of Beclin1
      and MAPLC3 mRNA in refractory or relapse patients is especially significant. This
      may be related to the genesis, development and drug resistance of AL.

PMID- 21729532
TI  - [Therapeutic effect of focal adhesion kinase gene silence on leukemia].
AB  - This study was aimed to investigate the effects of focal adhesion kinase (FAK)
      gene silence on leukemia cell growth, leukemogenesis and efficacy of chemotherapy
      drug. Vector containing lentiviral-FAK-shRNA was constructed and transfected into
      BCR/ABL-BaF3 leukemic cells, the cell growth and apoptosis were detected in
      vitro. The effect of FAK shRNA on leukemogenesis was studied in a murine model
      with leukemia. The apoptosis of leukemia cells and survival of leukemic mice
      treated by FAK shRNA combined with drug STI571 were monitored. The results showed
      that FAK gene expression was knocked down by lentiviral-FAK-shRNA. FAK gene
      silencing inhibited leukemia cell growth in vitro. The apoptosis test results
      showed that the percentages of Annexin V(+) cells in vector control group and FAK
      shRNA group were (3.46 +/- 0.56)% and (7.3 +/- 0.79)%, respectively, and the
      difference was statistically significant (p < 0.05). The mice in vector control
      group died at day 21 to 27, while the mice in FAK shRNA group died between day 52
      and 60, and the difference was statistically significant (p < 0.05). Moreover,
      FAK gene silence combined with drug STI571 could enhance the apoptosis of
      leukemia cells and prolong survival time of leukemic mice. It is concluded that
      FAK gene silence inhibits leukemogenesis and promotes efficacy of chemotherapy
      drug on leukemia cells, indicating FAK gene silence may be considered as a new
      therapeutic strategy for leukemia.

PMID- 21729533
TI  - [A new artemisinin derivative SM1044 induces apoptosis of Kasumi-1 cells and its
      mechanism].
AB  - The aim of this study was to investigate the apoptosis-inducing effect of
      artemisinin derivative SM1044 on Kasumi-1 cells and its possible mechanism.
      Kasumi-1 cells were treated with different concentrations of SM1044, the cell
      viability was evaluated by MTT assay. Cell apoptosis and cell cycle progression
      were assessed by using flow cytometry with Annexin-V/PI double staining and flow
      cytometry with PI staining respectively. The expression of apoptosis-related
      proteins caspase 3, PARP and the fusion protein AML1-ETO were detected by Western
      blot. The results indicated that SM1044 inhibited cell growth of Kasumi-1 cells
      in time- and dose-dependent manners. After exposure of Kasumi-1 cells to 1 umol/L
      SM1044 for 24 hours, the cell viability was decreased to 50%. IC(50) of SM1044 to
      Kasumi-1 cells at 48 hours was 0.17 +/- 0.067 umol/L. SM1044 induced cell
      apoptosis in a caspase-dependent manner, and the apoptotic rate of Kasumi-1 cells
      increased as SM1044 concentration increased. Flow cytometry with PI staining
      revealed that SM1044 induced cell cycle arrest, and the proportion of cells in
      G(0)/G(1) phase increased from 58.33 +/- 4.46% to 71.75 +/- 2.24% after exposure
      to 5 umol/L SM1044 for 24 hours. Western blot showed that SM1044 increased the
      expression of apoptosis-related proteins cPARP and cleaved caspase 3 and also
      degraded the AML1-ETO fusion protein. It is concluded that SM1044 can inhibit the
      proliferation of Kasumi-1 cells, induce cell apoptosis which may be related to
      the increased level of cleaved PARP and cleaved caspase 3. SM1044 can also induce
      cell arrest in G(0)/G(1) phase. As the fusion protein AML1-ETO degrades
      obviously, it can be the potential target of SM1044 in Kasumi-1 cells.

PMID- 21729534
TI  - [Effects of simvastatin on proliferation and apoptosis of acute monocytic
      leukemia cell line SHI-1].
AB  - The purpose of this study was to investigate the effect of simvastatin (SIM) on
      proliferation and apoptosis of acute monocytic leukemia cell line SHI-1 and its
      mechanism. Experiments were divided into control and test groups (5 umol/L, 10
      umol/L, 20 umol/L SIM groups). The growth inhibitory rate of SHI-1 cells was
      detected using methyl thiazolyl tetrazolium (MTT) method. The cell cycle
      distribution and apoptotic rate were measured by using flow cytometry. The
      expression of BCL-2, caspase-3 mRNA were determined by reverse transcription
      polymerase chain reaction (RT-PCR). The expression of BCL-2, caspase-3 protein
      levels were analyzed by Western blot. The results demonstrated that SIM inhibited
      the growth of SHI-1 cells in time- and does-dependent manners. Cell cycle
      analysis showed that SHI-1 cells significantly arrested in S phase (p < 0.05)
      after treating with SIM for 48 hours, as compared with control group. 5 umol/L
      SIM in test group significantly blocked cell cycle progression, but can not
      induce apoptosis. The expressions of BCL-2 mRNA and protein were down-regulated
      and caspase-3 mRNA and protein were up-regulated along with the increase of SIM
      concentration (p < 0.05). It is concluded that SIM is able to inhibit
      proliferation and induce apoptosis of SHI-1 cells, the mechanism may be
      associated with downregulating the expression of apoptosis-related gene BCL-2,
      upregulating the expression of caspase-3.

PMID- 21729535
TI  - [Mechanism of cinnamic aldehyde-inducing apoptosis of chronic myeloid leukemic
      cells in vitro].
AB  - The aim of this study was to investigate the apoptosis-inducing effect of
      cinnamic aldehyde (CA) on chronic myeloid leukemic (CML) cells and its mechanism.
      K562 cells and primary bone marrow mononuclear cells (MNC) from patients with CML
      were treated by various concentrations of CA. Flow cytometry was employed to
      measure the apoptosis of K562 cells and primary CML bone marrow MNC. Western blot
      was used to determine the expression of C-MYC and the phosphorylation of CrkL in
      K562 cells, and real-time polymerase chain reaction (real-time PCR) was used to
      quantify the expression of BCR-ABL mRNA in K562 cells. The results indicated that
      CA induced the apoptosis of K562 cells in a time- and dose-dependent manner. CA
      induced apoptosis of CML MNC dose-dependently. CA inhibited the expression of BCR
      ABL mRNA and C-MYC, reduced CrkL phosphorylation levels in K562 cells. It is
      concluded that CA induces apoptosis of CML cells in vitro. Down-regulation of the
      expression and function of BCR-ABL may be one of its most important anti-leukemia
      mechanisms.

PMID- 21729536
TI  - [Effects of hyperbaric oxygen combined with adriamycin in inducing apoptosis of
      K562/A02 cells].
AB  - This study was purposed to explore the effects of hyperbaric oxygen (HBO)
      combined with adriamycin (ADM) on inducing apoptosis of multidrug resistant cells
      line K562/A02. The cell apoptosis and expression of caspase-3 activity were
      analyzed by flow cytometry and transmission electron microscopy; the expression
      levels of HIF-1alpha, BCL-2 and BAX mRNA were detected by quantitative real time
      PCR; the caspase 8 activity was determined by using caspase 8 kit; the expression
      level of P-gp was detected by Western blot. The results showed that the apoptosis
      rate of K562/A02 cells in combination group (0.2 MPa HBO + ADM) was higher than
      that in ADM group [(47.36 +/- 3.87) % vs (28.51 +/- 1.09) %], the difference was
      statistical significant (p < 0.05); the expression levels of HIF-1alpha mRNA, P
      gp and BCL-2 in combination group were lower than those in ADM group, there were
      significant differences (p < 0.05); the activities of BAX, caspase 3 and caspase
      8 proteins in combination group were higher than those in ADM group, the
      difference was statistical significant (p < 0.05). It is concluded that 0.2 MPa
      HBO combined with ADM can reverse the drug-resistance of K562/A02 cells to ADM,
      enhance the apoptosis rate of cells. The molecular mechanism may be related with
      down-regulation of P-gp and BCL-2 expression, and up-regulation of caspase-3 and
      caspase-8 activities by HIF-1alpha.

PMID- 21729537
TI  - [Apoptosis-inducing Effect of 8-Bromo-7-Methoxychrysin on K562 cells].
AB  - This study was purposed to investigate the apoptosis-inducing effect of 8-bromo-7
      methoxychrysin (BrMChR) on leukemia K562 cells as well as the variation of
      caspase-3 activity and phosphorylated Akt (p-Akt) expression of K562 cells during
      the process of apoptosis. MTT assay was used to determine the inhibitory effect
      of BrMChR on proliferation of K562 cells. Cell apoptosis was assayed by AO/EB
      staining under fluorescent microscope and flow cytometry with Annexin V-FITC/PI
      staining. The expression level of p-Akt was measured by Western blot. The results
      showed that BrMChR had the inhibitory effect on proliferation of K562 cells and
      could induce apoptosis of these cells in dose-dependent manner, and these effects
      were significantly stronger than ChR. After treatment of K562 cells with 3 umol/L
      ChR for 12 hours, the apoptosis rate was only 3.68%, but the apoptosis rate of
      K562 cells treated with 3 umol/L BrMChR was 21.8%. In the same time, the caspase
      3 activity significantly increased (p < 0.05), but the expression of p-Akt was
      down-regulated (p < 0.01). It is concluded that BrMChR can induce apoptosis of
      K562 cells and with effect stronger than chR. P-Akt may participate in the
      apoptosis process of K562 cells induced by BrMChR.

PMID- 21729538
TI  - [Apoptosis-inducing effects of brucine on human chronic myeloid leukemia cell
      line K562].
AB  - To investigate the apoptosis-induction effect of brucine on human chronic myeloid
      leukemia cell line K562 cells, K562 cells were exposed to various dosages of
      brucine. MTT method was used to assayed the growth inhibition effect of brucine
      on K562 cells. The apoptosis of K562 cells was detected by acridine
      orange/ethidium bromide (AO/EB) double staining, Annexin-V/PI double labeling
      method and DNA agarose gel electrophoresis. The results showed that brucine could
      remarkably inhibit the K562 cell growth in a concentration-dependent and time
      dependent manners at the range of 50 to 400 ug/ml, and its most significant
      inhibition was observed at 400 ug/ml for 72 hours and the inhibition rate was
      94.0%. Staining of cells with AO-EB revealed that brucine induced nuclear
      chromatin condensation. After the K562 cells were treated with the brucine of 400
      ug/ml for 72 hours, the most of the nucleus were orange stained and condensation
      like or bead-like showing apoptotic morphology. The K562 cells treated with
      brucine of different concentrations (50, 100, 200, 400, 800 ug/ml) for 72 hours,
      Annexin-V/PI detection showed brucine could induce apoptosis of K562 cells, and
      apoptosis rate increased gradually with increasing concentration of drugs. The
      K562 cells treated with brucine of 400 ug/ml for 72 hours displayed typical
      ladder strap in DNA gel electrophoresis. It is concluded that brucine can
      efficiently inhibit cell growth and induce apoptosis of K562 cells with dose
      dependent manner in concentrations of 50 - 400 ug/ml.

PMID- 21729539
TI  - [Mechanism of Fas/FasL signal transduction pathway in K562 cell apoptosis induced
      by diallyl disulfide].
AB  - The aim of this study was to investigate the effect of diallyl disulfide (DADS)
      on the apoptosis of K562 cells and to explore the mechanism of K562 apoptosis
      induced by DADS. The K562 cells were treated with different concentrations of
      DADS for 24, 48 and 72 hours. The concentrations of DADS were as follows: 0
      (control group), 10, 20, 40 and 80 mg/L. The morphologic changes of leukemia K562
      cells treated with DADS were observed by Hoechst33 258 staining. The apoptosis of
      K562 cells treated with different concentrations of DADS for 24, 48 and 72 hours
      was analyzed by flow cytometry. The mRNA expression changes of Fas and FasL were
      detected by reverse transcription-polymerase chain reaction (RT-PCR) after K562
      cells were treated with different concentrations of DADS for 48 hours. The
      results indicated that the characteristics of apoptosis in K562 cells induced by
      DADS were as follows: reduction of nucleus, chromatin condensation and nuclear
      membrane rupture. The flow cytometry with PI straining showed that after 24 hours
      of DADS treatment the apoptosis rate of K562 cells increased from 11.60 +/- 0.83%
      at the concentration of 10 mg/L to 37.94 +/- 0.87% at the concentration of 40
      mg/L. The apoptosis rate of K562 cells increased from 37.94 +/- 0.87% (24 hours)
      to 47.02 +/- 0.66% (72 hours) after treatment with DADS of 10 mg/L increasing to
      40 mg/L DADS. The Fas mRNA expression levels of the related apoptotic genes
      increased after K562 cells were treated with different concentrations of DADS for
      48 hours, while FasL mRNA expression decreased significantly after DADS treatment
      for 48 hours, compared with those in the control group (p < 0.05). It is
      concluded that DADS can induce the apoptosis of human leukemia K562 cells in a
      time-and concentration-dependent manners. The activation of Fas/FasL pathway may
      play an important role in the K562 cell apoptosis induced by DADS, which is
      associated with increasing Fas gene expression and decreasing FasL gene
      expression.

PMID- 21729540
TI  - [Apoptosis-inducing effect of clostridium difficile toxin A on K562 cells and its
      mechanism].
AB  - This study was purposed to investigate the growth inhibition and apoptosis
      inducing effect of Clostridium difficile toxin A (TcdA) on the leukemia cell line
      K562. The proliferative activity of K562 cells exposed to Tcd A was tested by MTT
      assay, cell apoptosis was detected by flow cytometry; immunocytochemistry and
      colorimetric assay were employed to detect the protein expressions of BCL-2/BAX
      and the activity of Caspase-3, respectively. The results indicated that the
      proliferation of K562 cells was inhibited in a time-and dose-dependent manner
      after exposure to Tcd A for 24, 48 and 72 hours, the cells displayed the typical
      apoptotic, morphological changes, the expression of BCL-2 protein was down
      regulated but the expression of BAX protein was signficantly increased, compared
      with control group (p < 0.05). In addition, caspase-3 was activated in a
      concentration-dependent manner. It is concluded that Tcd A inhibits cell growth
      of K562 by inducing apoptosis, and the up-regulation of BAX protein and
      activation of caspase-3 may play important roles in these processes.

PMID- 21729541
TI  - [Apoptosis of KBM5R cell line with T315I point mutation induced by arsenic
      trioxide].
AB  - This study was aimed to investigate the inducing-apoptosis effect of arsenic
      trioxide (ATO) on imatinib (IM)-resistant chronic myeloid leukemia (CML) cell
      line KBM5R with T315I point mutation. CML cell line KBM5R with T315I point
      mutation and wild-type cell line KBM5 were selected for study. Resistance of
      KBM5R cells to IM and proliferation of KBM5 and KBM5R cells treated with ATO were
      detected by MTT; apoptosis of KBM5 and KBM5R cells were quantified by flow
      cytometry; the expression of apoptosis-related protein caspase-3, -8, -9 was
      determined by Western blot. The results showed that (1) IC(50) of KBM5R and KBM5
      cells treated with IM were 12.66 +/- 0.565 umol/L and 0.303 +/- 0.031 umol/L
      respectively, and significantly different from each other. (2) the proliferation
      of KBM5 and KBM5R cells treated with different concentrations of ATO was
      inhibited in dose- and time-dependent manners at 24, 48, 72, 96 hours, and
      inhibition of KBM5R cell proliferation was stronger than KBM5 in the same drug
      concentration and time. (3) the apoptosis rate of KBM5 and KBM5R cells treated
      with 2, 4, 8 umol/L ATO for 48 hours increased in a concentration-dependent
      manner, and the apoptosis rate of KBM5R was higher than that of KBM5 cells in the
      same drug concentration. (4) the expression of cleaved caspase-3, -8, -9 protein
      in KBM5 and KBM5R cells treated with 4 umol/L ATO for 24 hours significantly
      increased. It is concluded that KBM5R cells are significantly resistant to IM;
      ATO can inhibit the proliferation and induce the apoptosis of KBM5R and KBM5
      cells. As compared with wild-type KBM5 cells, effect of ATO on inhibition of
      proliferation and induction of apoptosis in KBM5R cells are more stronger. ATO
      can induce the apoptosis of KBM5 and KBM5R cells through the activation of
      apoptosis-related caspase-3, -8, -9 protein.

PMID- 21729542
TI  - [Mechanism of apoptosis of NB4 cells induced by arsenic trioxide and
      cyclooxygenase-2 expression].
AB  - Objective of this study was to investigate the changes of cyclooxygenase-2
      expression and mitochondrial membrane potential in apoptotic NB4 cells induced by
      arsenic trioxide (As(2)O(3)). The morphological changes in apoptosis process of
      NB4 cells treated by arsenic trioxide were observed under immunofluorescence
      microscope and DNA electrophoresis method, and the apoptosis rate of NB4 cells
      and the variations of mitochondrial membrane potential were detected by flow
      cytometry. Furthermore, the variations of expression level of cyclooxygenase-2
      protein were analyzed by using Western blot method. The results indicated that
      after NB4 cells were treated with 2 umol/L As(2)O(3) for 48 hours, some
      variations of NB4 cells were observed, such as pyknosis, chromatin segmentation,
      even fragmentation. Meanwhile, the typical DNA Ladder phenomenon was observed.
      The apoptosis rate of NB4 cells treated with 3 umol/L As(2)O(3) for 48 hours was
      33.34%, Furthermore the apoptosis rate of NB4 cells was enhanced along with the
      increase of concentration of As(2)O(3). After NB4 cells were treated with 0.5, 1,
      2, 4 and 8 umol/L As(2)O(3) for 48 hours, the mitochondrial membrane potential
      decreased by 12.8%, 21.6%, 66.9%, 83.7% and 83.8% respectively. The Western blot
      detection results showed that the expression level of cyclooxygenase-2 protein in
      NB4 cells was lower than that in control cells and decreased along with the rise
      of As(2)O(3) concentration, then the negative dose-dependent manner was observed
      between these 2 groups. It is concluded that As(2)O(3) can effectively induce NB4
      cell apoptosis, and the dose-dependent manner existed in certain extent of
      concentrations. The decrease of mitochondrial membrane potential may be related
      with NB4 cell apoptosis induced by As(2)O(3). Cyclooxygenase-2 participates in
      the process of NB4 cell apoptosis induced by As(2)O(3).

PMID- 21729543
TI  - [Glycyrrhetinic acid induces apoptosis and alters survivin gene expression in
      human myeloma cell line U266].
AB  - This study was aimed to investigate the effects of glycyrrhetinic acid (GA) on
      proliferation, apoptosis and survivin mRNA expression in human myeloma cell line
      U266 in vitro. Cell proliferation was assayed by MTT method. Both cell apoptosis
      and cell distribution in cell cycle were analyzed by using flow cytometry.
      Scanning electron microscopy was used to observe the morphological changes in
      U266 cells induced by GA. Expression of survivin mRNA was detected by
      quantitative real-time reverse transcription-polymerase chain reaction. The
      results showed that GA inhibited proliferation of U266 cells in a time- and dose
      dependent manners in vitro. GA presented apoptosis induction potency to U266
      cells, obvious changes in morphology of U266 cells was observed under scanning
      electron microscope. The cells were arrested at the G(0)/G(1) phase, showing the
      accumulation in G(0)/G(1) phase, reduction of cells in G(2)/M phase and S phase.
      GA could down-regulate the expression of survivin gene in U266 cells in a dose
      dependent manner. It is concluded that GA can inhibit proliferation of U266 cells
      in a time- and dose-dependent manners and induce apoptosis of this cell line in
      vitro through arresting G(0)/G(1) phase and down-regulating expression of
      survivin.

PMID- 21729544
TI  - [Early apoptosis of HL-60 cells induced by anti-CD44 McAb A3D8 inhibiting ERK1/2
      upregulated Bim expression].
AB  - This study was aimed to investigate the effects of anti-CD44 mAb A3D8 on
      proliferation and apoptosis of AML cells, to explore the mechanism of ERK1/2 and
      Bim in this process. Effect of the anti-CD44 mAb A3D8 on the HL-60 cell
      proliferation was assayed with MTT method, the change of mitochondrial
      transmembrane potential of HL-60 cells was analyzed by flow cytometry. The mRNA
      expression of Bim was determined by real-time quantitative RT-PCR. Western blot
      was used to detect the protein expression of p-ERK1/2. The results showed that
      mAb A3D8 could remarkably inhibit the proliferation capacity of the HL-60 cells
      in a dosage- and time-dependent ways. The mitochondrial transmembrane potential
      in HL-60 cells treated with A3D8 (3.0 ug/ml) was significantly decreased as
      compared with the control cells. Furthermore, the mRNA expression of Bim was much
      higher than that in controls. Expression of the p-ERK was much lower than that of
      the controls. It is concluded that anti-CD44 mAb A3D8 can inhibit the
      proliferation and induce the apoptosis of HL-60 cells, mechanism of which is
      enhancing the expression of Bim via inhibiting p-ERK1/2.

PMID- 21729545
TI  - [Inhibition of NHE1 promotes hypoxia-induced differentiation of K562 leukemic
      cells].
AB  - This study was purposed to investigate the effect of hypoxia microenvironment on
      K562 leukemic cell differentiation, and characteristics of NHE1 involvement in
      this process. The K562 cells were treated with hypoxia-mimical agent CoCl2 or
      under actual hypoxia culture, and the specific NHE1 inhibitor Cariporide was used
      to inhibit NHE1 activity. The fluorescent probe BCECF was used for pH(i)
      measurements. Gene expression was analyzed by RT-PCR. The morphological
      characteristics was determined by Wright's staining. Signaling pathways were
      detected by Western blot using phosphospecific antibodies. The results indicated
      that the hypoxia or mimetic hypoxia favored K562 cells differentiation with up
      regulation of C/EBPalpha. Moreover, treatment with Cariporide under hypoxia
      synergistically enhanced leukemia cell differentiation. Treatment with Cariporide
      increased levels of phosphorylated ERK5 and P38 mitogen-activated protein kinase
      (MAPK). It is concluded that the hypoxia or mimetic hypoxia can induce the
      differentiation of K562 cells, the inhibition of NHE1 activity can promote the
      hypoxia-induced K562 cell differentiation. The enhancement of hypoxia-induced
      K562 differentiation by Cariporide via MAPK signal pathway suggests a possible
      therapeutic target of NHE1 under hypoxia microenvironment in the treatment of
      leukemias.

PMID- 21729546
TI  - [Reversal of multidrug resistance in HL-60, MSC and CD34(+) cells from umbilical
      cord blood by sustained intracellular acidification].
AB  - The aim of this study was to investigate the effect of intracellular
      acidification on accumulation of rhodamine 123 (rh123) in non-mature cells with
      none or low expression of multidrug resistance MDR1. The expression of MDR1 mRNA
      was detected by real-time quantitative RT-PCR. Confocal laser microscopy was used
      to determine the calibration curve of intracellular acidification (pHi). MTT
      assay was used to detect the cytotoxicity of intracellular acidification on HL
      60, MSC and CD34(+) cells from umbilical cord blood. Flow cytometry was applied
      to measure the influence of intracellular acidification. The results indicated
      that the intracellular acidification had no obvious cytotoxicity on HL-60, MSC
      and CD34(+) cells. The acidification resulted in the increased rhodamine 123
      accumulation in HL-60, MSC and CD34(+) cells without P-gp activity. Moreover, the
      more primitive cells, the less accumulation of intracellular Rh123 were observed.
      It is concluded that the intracellular acidification can reverse the MDR of HL
      60, MSC and CD34(+) cells.

PMID- 21729547
TI  - [Effect of different concentrations of bortezomib on the expression of ERK, JNK
      and P38 in daunorubicin-resistant K562 cells].
AB  - The aim of this study was to investigate the effect of proteasome inhibitor
      bortezomib on the expression of ERK, JNK, and P38 in daunorubicin (DNR)-resistant
      K562 cells and its mechanism. MTT method was used to determine the drug-resistant
      K562 cells and the cellular toxicity of bortezomib; Western blot was used to
      detect the expression of protein ERK, JNK and P38 in K562 cells after treatment
      with 100 nmol/L DNR alone or combined with 1 nmol/L and 10 nmol/L bortezomib for
      36 hours. Flow cytometry assay was used to detect the apoptosis rate in each
      group cells. The results indicated that the expression of ERK and P38 were
      significantly suppressed (p < 0.05) and the expression of JNK was significantly
      enhanced (p < 0.05) in the cells treated by DNR combined with bortezomib. It is
      concluded that bortezomib can decrease the expressions of protein ERK and P38 and
      enhance the expression of JNK, the bortezomib reverses the cellular drug
      resistance and promote cell apoptosis through MAPK pathway.

PMID- 21729548
TI  - [Change of serum immunoglobulin level in patients with diffuse large B cell
      lymphoma after rituximab combined with chemotherapy].
AB  - This study was purposed to investigate the changes of serum immunoglobulin (Ig)
      level during treatment of diffuse large B cell lymphoma by using rituximab (RTX)
      combined with CHOP. Total of 122 newly diagnosed patients with CD20(+) diffuse
      large B cell lymphoma from January 2004 to December 2009 were analyzed
      retrospectively. According to different treatment regimens, 122 patients were
      divided into 2 group: group treated with CHOP (n = 24) and group treated with R
      CHOP (n = 98, out of which 16 patients with abnormal Ig levels before treatment).
      Ig levels of patients in 2 groups at different stages were recorded and analyzed
      after abandoning those patients with abnormal Ig levels before treatment. The
      results showed that after 6 cycles of treatment, among the total 82 patients with
      normal levels of serum immunoglobulin, the decreased levels of IgG, IgA and IgM
      by 20% of baseline value were found in 85.4% (70/82), 85.4% (70/82) and 87.8%
      (72/82) patients respectively, while levels of IgG, IgA and IgM < low limit of
      normal value were observed in 47.6% (39/82), 48.8% (40/82) and 52.4% (43/82)
      patients respectively. No obvious changes of IgG, IgA and IgM levels were found
      in 24 patients of CHOP group before and after treatment.It is concluded that
      hypogammaglobulinemia is a common complication in chemotherapy using RTX combined
      with CHOP, the decreased level of Ig is recovered to normal level about 1 year
      after stop of treatment, the decrease of Ig in some cases can last even for over
      2 years.

PMID- 21729549
TI  - [Hyperthermia increases the sensitivity of RPMI 8226 cells to adriamycin].
AB  - This study was purposed to explore the effect of hyperthermia on sensitivity of
      multiple myeloma cells RPMI 8226 to adriamycin (ADM) and its mechanism. The
      working concentration of ADM against RPMI 8226 cells was defined by MTT assay.
      RPMI 8226 cells were divided into 4 groups: control group, hyperthermia (42
      degrees C) group, chemotherapy (ADM) group and combination group (42 degrees C +
      ADM), the survival rate of RPMI 8226 cells in 4 groups was detected by trypan
      blue exclusion, the inhibitory effect of hyperthermia on proliferation of RPMI
      8226 cells was detected by MTT assay, the cell cycle distribution, apoptosis rate
      of cells, intracellular ADM concentration and P-gp expression level were measured
      by flow cytometry. The 1/4 IC(50) of ADM was defined as the working concentration
      in the experiment. The results indicated that the hyperthermia promoted the
      entering the cells from in G(0)/G(1) phase into S and G(2)/M phases, the
      expression of P-gp protein on cells in hyperthermia and combination groups was
      down-regulated, the intracellular ADM concentration in combination group
      obviously increased. It is concluded that the hyperthermia combined with ADM
      obviously enhance the inhibitory effect on proliferation of RPMI 8226 cells. The
      hyperthermia increases the sensitivity of RPMI 8226 cells to chemotherapy through
      down-regulating the expression of P-gp protein on cells and increasing the
      intracellular ADM concentration.

PMID- 21729550
TI  - [Effect of curcumin in combination with bortezomib on proliferation and apoptosis
      of human multiple myeloma cell line H929 and its mechanism].
AB  - This study was aimed to investigate the effect of curcumin in combination with
      bortezomib on the proliferation and apoptosis of human MM cell line H929 in
      vitro, and to explore its mechanisms. MTT assay was applied to detect the
      inhibitory effects of curcumin and bortezomib either alone or combined at
      different concentrations on H929 cells, and flow cytometry was employed to assay
      the apoptosis rate. In addition, RT-PCR was used to analyze the mRNA expression
      of gene BCL-2, BAX, cyclin D1. Immunofluorescence technique was performed to
      study the location changes of NF-kappaB P65 in different groups. The results
      showed that both curcumin and bortezomib inhibited the proliferation of MM cell
      line H929 in dose-dependent manner, and combination of these two drugs displayed
      synergistical effect. A much higher apoptosis rate was determined by flow
      cytometry in combinative groups than that in single or control group. And RT-PCR
      showed, as compared with curcumin or bortezomib group, there was mRNA expression
      decrease of BCL-2, cyclin D1 but increase of BAX in combined group. The
      expression of NF-kappaB P65 in nucleus was downregulated in either the curcumin
      or bortezomib group, however, distribution of NF-kappaB P65 in cytoplasm was
      observed in combined group. It is concluded that the combination of curcumin and
      bortezomib is much more effective for the inhibiting proliferation and promoting
      apoptosis of H929 cell line, which may function by inhibiting the transcription
      of NF-kappaB and apoptosis-related genes.

PMID- 21729551
TI  - [Influence of immunosuppressive therapy on expression of TNF-alpha/IFN-gamma in
      cytoplasm of peripheral blood lymphocytes of patients with aplastic anemia].
AB  - The purpose of this study was to investigate the influence of immunosuppressive
      therapy on the expression of TNF-alpha/IFN-gamma in cytoplasm of peripheral blood
      lymphocytes of patients with aplastic anemia (AA). The expression of TNF-alpha
      and IFN-gamma in cytoplasm of peripheral CD3(+) lymphocytes were measured by flow
      cytometry in 25 cases of de novo AA patients and 20 cases of AA after
      immunosuppressive therapy. The results showed that the positive rates of
      CD3(+)/TNF-alpha(+) and CD3(+)/IFN-gamma(+) in de novo AA patients were (5.97 +/-
      6.78)% and (15.20 +/- 11.28)% respectively, and (1.56 +/- 0.87)% and (1.76 +/-
      0.87)% in normal controls respectively. There was significant difference between
      de novo AA patients and normal controls (p < 0.05). The positive rates of
      CD3(+)/TNF-alpha(+) and CD3(+)/IFN-gamma(+) in immunosuppressive therapy group
      were (1.67 +/- 1.26)% and (4.35 +/- 4.33)% respectively. The difference between
      immunosuppressive therapy group and de novo AA group was statistically
      significant (p < 0.05). It is concluded that the levels of intracellular TNF
      alpha and IFN-gamma in AA patients are higher than those in normal controls.
      Immunosuppressive therapy significantly reduces the expression of intracellular
      TNF-alpha and IFN-gamma. Its relationship with the clinical treatment is worth
      further observing.

PMID- 21729552
TI  - [Large sample clinical analysis of patients with children acute leukemia in
      single center].
AB  - In order to investigate the epidemiology of childhood acute leukemia (CAL), such
      as onset age and time, risk factor, subtypes distribution and genetics, 1236 CAL
      patients admitted in blood disease hospital of Chinese Academy of Medical
      Sciences for treatment from April 2004 to April 2010 were analyzed
      retrospectively. The results showed that the sex ratio of ALL and AML patients
      were 1.80:1 and 1.73:1 respectively; the average peak age of incidence lasted
      from 2 to 6 years with the median age of 6 years, while the ALL peak age of
      incidence lasted from 2 to 5 years but AML showed no significant peak age of
      incidence. Winter, especially January was the peak time for both onset and birth.
      Among all the 631 ALL patients who had already been immunophenotyped, B-ALL
      patients accounted for 83%, T-ALL patients accounted for 9%. Among 361 AML
      patients, sub-leukemia phenotype from M(0) to M(7) accounted for 0.3%, 2.2%,
      29.8%, 20.9%, 8.1%, 25.2%, 4.1% and 4.6% respectively. Among 631 pediatric ALL
      patients who had been examined by using molecular biology technique, the positive
      rate of TEL/AML1, BCR/ABL, MLL and E2A/PBX1 were 23%, 7.4%, 4.1%, 2.1%
      respectively. Among 361 pediatric AML patients who had been examined by using
      molecular biology technique, 19% of the patients showed positive AML1/ETO fusion
      gene, 18% of the patients showed positive PML/RARalpha fusion gene, while 4.2% of
      patients showed positive CBFbeta/MYH11. It is concluded that the onset of
      pediatric acute leukemia is influenced by age, season, environment and different
      genetic background.

PMID- 21729553
TI  - [Immunophenotypes in 207 pediatric patients with ALL and theirs correlation with
      cytogenetics and clinical features].
AB  - The objective of this study was to investigate the immunophenotypic subtype
      profiles of 207 pediatric patients with acute lymphoblastic leukemia (ALL) and
      its correlation with cytogenetics and clinical features. 207 children with ALL
      were immunophenotyped by four color flow cytometry using a panel of monoclonal
      antibodies. 207 patients were enrolled in this study, out of which 146 cases were
      subjected to karyotype analysis by R-banding technology. The results showed that
      11.6% out of 207 children with ALL were identified as T-ALL, 88.4% as B-ALL.
      Myeloid antigen (MyAg) expression was documented in 42.5% out of 207 cases
      analyzed and CD13 was the most commonly expressed MyAg (31.4%). No difference was
      observed in the expression of MyAg between the groups of patients with T-ALL
      (41.7%) and B-ALL (42.6%). Abnormal karyotypes were detected in 84 out of 146
      (57.5%) children. The clinical and biological characteristics of ALL patients
      between MyAg(+) and MyAg(-) groups showed that higher percentage of patients with
      high WBC count (> 50 * 10(9)/L) and higher CD34 positivity were found to be
      correlated with MyAg(+) ALL. It is concluded that immunophenotype analysis is
      useful for ALL diagnosis and classification, and the immunophenotypes are in
      relevance to the abnormal cytogenetic changes as well as clinical features in
      childhood ALL.

PMID- 21729554
TI  - [C742T mutation of alpha1, 3 N-acetyl-D-galactosaminyltransferase gene is
      responsible for A2 subgroup].
AB  - The objective of this study was to analyze the molecular genetic basis for 2
      individuals with A2B phenotype of ABO subtype. The ABO group antigens on red
      blood cells were identified by monoclonal antibodies and the ABO antibodies in
      serum were detected by the standard A, B, O cells. The exon 5 to exon 7 coding
      region of ABO gene was amplified by polymerase chain reaction (PCR) and the PCR
      product was sequenced directly after the enzymes digested. The amplified product
      was also cloned by TOPO TA cloning sequencing kit to split the 2 alleles apart
      and chosen colonies were sequencing bidirectionally for exon 6 to 7 of ABO gene.
      The results showed that both A and B antigen were identified on red blood cells
      of the individuals and there was anti-A1 antibody in their serum. There was no
      261G deletion and showed 297A/G, 467C/T, 526C/G, 657C/T, 703G/A, 742C/T, 796C/A,
      803G/C, 930G/A heterozygotes by direct DNA sequencing. After cloning and
      sequencing, it was obtained the B101 and one novel A allele. The novel allele has
      one nucleotide change at 742 position C to T compared with A102, which results in
      an amino acid Arg to Cys at 248 position and was nominated as A213. It is
      concluded that C742T mutation of the alpha1, 3 N-acetyl-D-galactosaminyl
      transferase gene can lead to A2 phenotype and with anti-A1 antibody in serum.

PMID- 21729555
TI  - [Packaging of lentivirus carrying gene hbetac and overexpression of gene hbetac
      in NB4 cells].
AB  - This study was aimed to overexpress gene hbetac in NB4 cells via the method of
      lentivirus-mediated gene transfer, to observe the differentiation behaviour
      change of hbetac over-expressing NB4 cells treated with IL-3 or GM-CSF, to
      explore the relationship between hbetac gene and the differentiation behaviour of
      NB4 cells. The targeted hbetac gene was amplified by PCR from the cloned vector
      carrying ORF of hbetac. The PCR product containing PmeI and BstBI site introduced
      by primer was digested, and then cloned into lentivirus vector
      pRRLSIN.cPPT.PGK/IRES/GFP.WPRE to construct a lentiviral vector carrying hbetac,
      named pLV-hbetac. And the pLV-hbetac plasmid was confirmed by restriction and
      sequencing. The recombinant lentivirus was produced by co-transfecting three
      plasmids into 293T packing cells. After transfection, the lentiviral supernatant
      was collected to transfect NB4 cells. GFP expression was examined by fluorescent
      microscope and the expression of hbetac gene was detected by Western blot. Then,
      the NB4 cells over-expressing hbetac were treated with IL-3 (10 ng/ml), GM-CSF
      (10 ng/ml), ATRA (1 umol/L) respectively, and the CD11b expression, morphology
      and differentiation behaviour changes of every groups were observed by flow
      cytometry and microscopy, while NB4 cells transfected with blank lentivirus (NB4
      blank cells) were used as controls. The results showed that the recombinant
      lentivirus vector carrying hbetac gene could efficiently transfect NB4 cells and
      made NB4 cells to stably over-express hbetac gene. The expression of CD11b was up
      regulated in NB4-hbetac cells treated with of IL-3 or GM-CSF, but it was not as
      obvious as the effect of ATRA, and no morphological change was observed in NB4
      hbetac cells treated with the IL-3 or GM-CSF. It is concluded that IL-3 or GM-CSF
      can induce NB4 cells over-expressing hbetac to differentiate to neutrophils, but
      can not make them fully matured.

PMID- 21729556
TI  - [Prediction and bioinformatics analysis of human gene expression profiling
      regulated by amifostine].
AB  - Objective of this study was to perform bioinformatics analysis of the
      characteristics of gene expression profiling regulated by amifostine and predict
      its novel potential biological function to provide a direction for further
      exploring pharmacological actions of amifostine and study methods. Amifostine was
      used as a key word to search internet-based free gene expression database
      including GEO, affymetrix gene chip database, GenBank, SAGE, GeneCard, InterPro,
      ProtoNet, UniProt and BLOCKS and the sifted amifostine-regulated gene expression
      profiling data was subjected to validity testing, gene expression difference
      analysis and functional clustering and gene annotation. The results showed that
      only one data of gene expression profiling regulated by amifostine was sifted
      from GEO database (accession: GSE3212). Through validity testing and gene
      expression difference analysis, significant difference (p < 0.01) was only found
      in 2.14% of the whole genome (460/192000). Gene annotation analysis showed that
      139 out of 460 genes were known genes, in which 77 genes were up-regulated and 62
      genes were down-regulated. 13 out of 139 genes were newly expressed following
      amifostine treatment of K562 cells, however expression of 5 genes was completely
      inhibited. Functional clustering displayed that 139 genes were divided into 11
      categories and their biological function was involved in hematopoietic and
      immunologic regulation, apoptosis and cell cycle. It is concluded that
      bioinformatics method can be applied to analysis of gene expression profiling
      regulated by amifostine. Amifostine has a regulatory effect on human gene
      expression profiling and this action is mainly presented in biological processes
      including hematopoiesis, immunologic regulation, apoptosis and cell cycle and so
      on. The effect of amifostine on human gene expression need to be further
      testified in experimental condition.

PMID- 21729557
TI  - [Simultaneous detection of FLT3-ITD and NPM1 gene mutations in acute myeloid
      leukemia by double PCR].
AB  - Objective of this study was to establish a method for simultaneous detection of
      FLT3/ITD and NPM1 gene mutations in AML. A double PCR was firstly designed and
      optimized to amplify both exon 12 of NPM1 and exon 14-intron 14-exon 15 of FLT3,
      with the aim of detecting almost all reported mutations. After optimization, a
      touchdown PCR was chosen for the multiplex PCR procedure, with the primer
      concentrations of NPM1 and FLT3-ITD being 200 nmol/L and 152 nmol/L respectively.
      The PCR amplicons were separated by capillary electrophoresis and the presence of
      mutants was recognized by the size difference between the mutants and wild-type
      products. The areas of mutant peak and wild-type peak were used to calculate the
      mutant/wild-type ratio. All the positive mutated samples were confirmed by
      sequencing. The results showed that 17 patients with NPM1 mutation, 15 patients
      with FLT3-ITD mutation, 6 patients with both NPM1 and FLT3-ITD mutations were
      found among 93 patents. 7 patients with M2, 4 patients with M4, 5 patients with
      M5 and 1 patients with M6 were found out of 17 patients with NPM1 mutation, in
      which 10 patients were male and 7 patients were female, 15 patients were with
      type A, 1 patients was with type B and 1 patients was with type Nm, strikingly 1
      CML patient in blast crisis was found to carry a type A mutation. Among 15
      patients with FLT3-ITD mutation 1 patient with M1, 8 patients with M2, 2 patients
      with M2, 2 patients with M3, 1 patient with M4, 3 patients with M5 were found, in
      which 5 patients were male and 10 patients were female. Sequencing results
      further confirmed the accuracy and reliability of this method. It is concluded
      that a novel method with the ability to detect both FLT3-ITD and NPM1 mutations
      has been developed when genomic DNA was templated. This method is fast, easy,
      accurate and capable to calculate the mutant/wild-type ratio.

PMID- 21729558
TI  - [Construction and identification of a eukaryotic expression vector containing
      human homeobox gene].
AB  - In order to investigate the special role of HOXB4 in expansion and self renewal
      of hematopoietic stem cells, the cDNA of HOXB4 was extracted and cloned from
      umbilical cord blood mononuclear cells by using RT-PCR. Then the eukaryotic
      expression bicistronic plasmid vector pIRES2-EGFP/HOXB4 was designed and
      constructed after cutting HOXB4 and pIRES2-EGFP respectively by restriction
      enzyme EcoRI and BamHI. The recombinant plasmid was delivered into competent
      cells of Escherichia coli. The successful construction of plasmid was confirmed
      by the identification of endonuclease cutting and sequencing. The results showed
      that the HOXB4 cDNA was cloned successfully from umbilical cord blood mononuclear
      cells and the recombinant eukaryotic expression bicistronic plasmid vector was
      constructed, and then introduced it into 293T cells successfully. It is concluded
      that a pIRES2-EGFP/HoxB1 eukaryotic expression bicistronic plasmid vector has
      been constructed successfully, which results provide a useful material basis for
      exploration of HoxB4 function in the proliferation and differentiation of
      hematopoietic cells.

PMID- 21729559
TI  - [Antitumor effect of BCG on growth of transplanted human myeloid leukemia HL-60
      cells in nude mice].
AB  - This study was purposed to explore the anti-leukemia effect of bacillus calmette
      guerin vaccine (BCG) on the human myeloid leukemia cell xenograft models. An
      animal model was established by inoculating the human myeloid leukemia HL-60
      cells into the BALB/c (8 - 10 weeks of age) nude mice. The mice were randomly
      divided into two groups: control group and experimental group. Nude mice in
      control group were injected with physiological saline, while those of
      experimental group were given BCG and inactivated BCG respectively. The tumor
      growth was assayed by using caliper. The survival time of nude mice was
      determined. Necrotic extent and morphological changes of tumor were observed and
      examined by HE staining and immunohistochemical method. The results indicated
      that on 5th-7th days after tumor inoculated, 2 - 3 mm tumor mass could be
      observed. The tumor volume increased over the time. HE staining of tumor tissues
      showed that there were different degrees of tumor necrosis in BCG group and
      inactivated BCG group. Immunohistochemistry results demonstrated that CD20
      positive cells were obviously observed in the necrotic area of BCG group,
      compared with the control group and inactivated BCG group. It is concluded that
      human myeloid leukemia HL-60 cells have been successfully transplanted in nude
      mice, and the systemic metastasis occurs along with the prolongation of time. BCG
      inoculation can delay the tumor growth and prolong the survival time of nude mice
      with leukemia, suggesting that BCG has an antitumor effect.

PMID- 21729560
TI  - [Imbalance of Th17/Treg cells ratio in peripheral blood of patients with immune
      thrombocytopenia].
AB  - The aim of this study was to investigate the expression of Th17 cells and
      regulatory T (Treg) cells in peripheral blood of patients with immune
      thrombocytopenia (ITP) and to clarify the role of the Th17/Treg cell ratio
      imbalance in pathogenesis of ITP. Patients were divided into the pre-treatment
      group (active group) (n = 38) and post-treatment group (remission group)
      according to the platelet count and curative effect. Post-treatment group was
      further divided into remission group (n = 24), partial remission group (n = 10),
      and non-remission group (n = 4). 30 healthy subjects were enrolled in control
      group. Flow cytometry was used to detect the percentages of peripheral blood Th17
      cells and Treg cells in CD4(+) T cells from ITP patients and controls
      respectively. The results showed that the percentages of Th17 cells in active
      group and non-remission group were significantly higher than those in control
      group (p < 0.05). The percentages of Th17 cells in remission group, partial
      remission group were also higher than those in control group, but there were no
      statistically significant differences between these groups. The percentage of
      Th17 cells in remission group was lower than that in active group, but there was
      also no statistically difference between two groups. The percentages of Treg
      cells in active group, partial-remission group and non-remission group
      significantly decreased, compared with in control group (p < 0.01). The
      percentage of Treg cells in remission group was lower than that in control group,
      but there was no statistically significant difference. The ratio of peripheral
      blood Th17/Treg cells in active group, partial-remission group and non-remission
      group was higher, as compared with in control group. The ratio of peripheral
      blood Th17/Treg cells in remission group was higher than that in control group,
      but there was no statistically difference between two groups. It is concluded the
      percentage of Th17 cells and the ratio of Th17/Treg cells are higher in active
      group. The percentage of Treg cells is low in active group, partial remission and
      non-remission groups. The imbalance of Th17/Treg ratio may play a critical role
      in ITP pathogenesis.

PMID- 21729561
TI  - [Detecting anti-megakaryocyte antibodies in serum of systemic lupus erythematosus
      patients by indirect immunofluorescence].
AB  - This study was purposed to investigate the mechanism of thrombocytopenia in
      patients with systemic lupus erythematosus (SLE) through detecting anti
      megakaryocyte antibodies in SLE patients. The serum anti-megakaryocyte antibodies
      in 36 SLE cases with thrombocytopenia were detected by using indirect
      immunofluorescence, the detected results were compared with detected results of
      30 SLE cases without thrombocytopenia and 30 healthy persons. The results showed
      that the positive incidences of anti-megakaryocyte antibody in serum of 36 SLE
      cases with thrombocytopenia, 30 SLE cases without thrombocytopenia and 30 healthy
      persons were 19.4% (7/36), 6.7% (2/30) and 3.3% (1/30) respectively. As compared
      with SLE patients without thrombocytopenia and healthy persons, SLE patients with
      thrombocytopenia had higher incidence of anti-megakaryocyte antibodies, moreover
      there was significant difference between SLE patients with thrombocytopenia and
      healthy persons (p < 0.05), while there was no significant difference between SLE
      patients with or without thrombocytopenia (p > 0.05). It is concluded that
      autoantibodies against megakaryocytes exist in SLE patients and may partially
      contribute to the incidence of thrombocytopenia in SLE patients. The detection of
      anti-megakaryocyte antibodies with a enough case number is needed to make a final
      conclusion on thrombocytopenia pathogenesis in SLE.

PMID- 21729562
TI  - [Effect of erythropoietin on proinflammatory factors of human monocytes and its
      mechanisms].
AB  - Erythropoietin (EPO) is the major means of treating anemia of chronic disease
      (ACD) through stimulating hematopoiesis, inhibiting hepcidin and decreasing
      proinflammatory factors. Recently, it has been found that monocytes are another
      source of hepcidin. EPO can reduce the hepcidin stimulated by IL-6 in monocytes,
      it is assumed that EPO can reduce hepcidin indirectly by reducing IL-6. However,
      the specific mechanism of EPO inhibiting the proinflammatory cytokines in
      monocytes is unclear now. This study was purposed to investigate the effect of
      EPO on monocyte proinflammatory factors and its molecular mechanism. IL-6 mRNA
      and TNF-alpha mRNA were detected by real time PCR, level of signaling molecule
      PARP-1 protein was detected by Western blot. THP-1 monocytes were stimulated by 1
      ug/ml lipopolysaccharide (LPS) to observe the impact of EPO at different
      concentrations (0.5, 1, 2, 5, 10 U/ml) for different time (0, 3, 6, 12, 24 hours)
      on the expression of IL-6 mRNA, TNF-alpha mRNA and PARP-1 protein. 1 ug/ml or 5
      ug/ml EPO receptor (EPOR) antibody and/or 3-aminobenzamide (3-AB, PARP-1
      inhibitor) were added to observe the antagonistic effect on EPO and the impact on
      PARP-1. The results showed that LPS could stimulate the THP-1 cells. EPO could
      decrease the levels of IL-6 and TNF-alpha stimulated by LPS in a dose- and time
      dependent manners. The most significant decrease in IL-6 mRNA expression was
      observed in 2 U/ml EPO for 6 hours. And down-regulation of TNF-alpha mRNA
      expression was pronounced at 10 U/ml EPO for 3 hours. IL-6 mRNA expression could
      be stimulated by LPS, PARP-1 protein was induced at the same time. EPO inhibited
      the expression of IL-6 mRNA, while PARP-1 protein also decreased. Down-regulation
      of IL-6 mRNA and PARP-1 protein level was pronounced at 2 U/ml EPO for 6 hours.
      3AB is a direct inhibitor of PARP-1. Similar to 3AB, EPO receptor antibody could
      antagonize the decline of IL-6 induced by EPO. It is concluded that EPO can
      inhibit the expression of IL-6 and TNF-alpha in monocytes, and the inhibition of
      IL-6 expression may be associated with decrease of PARP level.

PMID- 21729563
TI  - [Umbilical cord mesenchymal stem cell transplantation for treatment of
      experimental autoimmune myasthenia gravis in rats].
AB  - Umbilical cord mesenchymal stem cell (UCMSC) transplantation has been widely used
      in the treatment of a variety of diseases due to their advantages such as
      abundant resources, low immunogenicity and large ex vivo expansion capacity. This
      study was aimed to investigate the effects of UCMSC on experimental autoimmune
      myasthenia gravis (EAMG) rats. The distribution of human-derived cells was
      observed by immunofluorescence method, the effect of MSC on B-cell in situ
      secreted antibodies was assayed by ELISPOT, the secreted IFN-gamma level was
      detected by using Transwell test. The results showed that UCMSC were able to
      migrate to inflammation region and lymph nudes, moreover human-derived cells
      could be detected in medulla zone of lymph nudes. In vitro in situ detection of
      AchR specific antibody secretion revealed that the full contact of MSC with
      lymphnode-derived lymphocytes could effectively inhibit production of AchR
      antibody. Transwell test indicated that the direct contact of UCMSC with CD4 T
      cells could effectively decrease production of IFN-gamma, which modulated the
      unbalance between Th1/Th2 to a certain extent. It is concluded that UCMSC can
      regulate the immune system by direct cell-cell contact or/and release of
      cytokines, which bring a new insight into knowledge about MSC-based therapy for
      EAMG.

PMID- 21729564
TI  - [Application of short-tandem-repeat amplification and fluorescent-multiplex PCR
      for chimerism analysis].
AB  - The purpose of this study was to detect chimerism status of patients received
      allogeneic hematopoietic stem cell transplantation by using short tandem repeat
      (STR) amplification and fluorescence labeling multiplex polymerase chain reaction
      (PCR) combined with capillary electrophoresis, and to evaluate the prognostic
      value of monitoring chimerism status. DNA from peripheral blood or bone marrow of
      donors and recipients in different time were extracted, 10 different STR markers
      were co-amplified in a single reaction by using AmpFSTR Profiler Plus PCR
      amplification kits. Separation of the PCR products and fluorescence detection
      were performed by ABI PRISM 310 Genetic Analyzer with capillary electrophoresis.
      The Genescan and Genotype software were used for size calling and quantification
      of peak areas. The formula to calculate donor chimerism levels was based on the
      different allelic distribution types between donor and recipient. The results
      showed that 29 patients obtained complete donor chimerism and one patient
      obtained mixed chimerism in 28 days after transplantation. 22 patients continued
      complete donor chimerism and 8 patients showed mixed chimerism after long time
      follow up. 7 patients showed disease relapse after turning mixed chimerism from
      complete donor chimerism. The incidence of GVHD was higher in group of full donor
      chimerism. It is concluded that STR fluorescent-multiplex PCR is a rapid,
      automatic and sensitive method for chimerism tests after hematopoietic stem cell
      transplantation, which is a valuable tool as a dynamic monitoring for chimerism
      status to predict graft failure, disease relapse and occurrence of GVHD, and
      provides a basis for early clinical intervention in patients with allo-HSCT.

PMID- 21729565
TI  - [Analysis of post-thaw infused cell dose for predicting engraftment after
      unrelated cord blood transplantation].
AB  - This study was purposed to investigate the role of post-thaw infused donor cells
      for predicting engraftment and hematopoietic reconstitution after unrelated cord
      blood transplantation (UCBT). The retrospective analysis was performed on
      clinical data of 97 children with malignant or non-malignant diseases received
      single unit UCBT from August 1999 to April 2010. The impact of pre-freezing and
      post-thaw cell dose of total nucleated cells (TNC), CD34(+) cells and colony
      forming units-granulocyte/macrophage (CFU-GM) on engraftment and hematological
      recovery after UCBT was analyzed. Unrelated donors were from Guangzhou cord blood
      bank (GZCBB) entirely. The results indicated that the pre-freezing TNC (/kg)
      (mean +/- SD: 7.65 * 107 +/- 4.26 * 107; median: 6.34 * 107), CD34(+)cells (/kg)
      (mean +/- SD: 4.64 * 10(5) +/- 4.47 * 105; median: 3.03 * 105) and CFU-GM (/kg)
      (mean +/- SD: 0.79 * 105 +/- 1.09 * 105; median: 0.57 * 105) showed a good
      correlation with their post-thaw counterparts including TNC(/kg) (mean +/- SD:
      6.98 * 107 +/- 4.12 * 107; median: 6.00 * 107), CD34(+)cells (/kg)(Mean +/- SD:
      6.86 * 105 +/- 8.56 * 105; Median: 4.17 * 105), and CFU-GM (/kg) (mean +/- SD:
      0.52 * 105 +/- 0.52 * 105; median: 0.39 * 105) (r = 0.952, p < 0.001; r = 0.794,
      p < 0.001; r = 0.478, p < 0.001). Either the pre-freezing or post-thaw number of
      infused CFU-GM was significant higher in patients who achieved engraftment (n =
      70) than those who suffered graft failure (n = 22) (p = 0.023 and 0.011,
      respectively), but no significant difference of TNC and CD34(+) cells dose (pre
      freezing or post-thaw) were found between these two groups. Pre-freezing CFU-GM,
      TNC, CD34(+) cell dose negatively correlated with the time of neutrophil
      engraftment (r = -0.285, p = 0.018; r = -0.396, p = 0.002; r = -0.373, p =
      0.002), as well as the post-thaw number of TNC and CD34(+) cells (r = -0.260, p =
      0.031; r = -0.483, p < 0.001), whereas only pre-freezing CD34(+) cells showed a
      significant correlation with platelet engraftment time (r = -0.352, p = 0.013).
      It is concluded that the CFU-GM amount is useful for predicting engraftment of
      UCBT, while pre-freezing hematopoietic cell doses show superior correlation with
      the speed of engraftment and hematopoietic reconstitution than their post-thaw
      counterparts in pediatric recipients, suggesting that it is essential to perform
      hematopoietic potency assay on each cord blood unit prior to listing or release
      for administration.

PMID- 21729566
TI  - [Yield of CD34(+) cells in graft can be increased significantly by G-CSF used at
      appropriate time after chemotherapy for AutoPBSCT].
AB  - This study was aimed to investigate the influence of timing using G-CSF after
      chemotherapy on graft yield of mobilized peripheral blood stem cells for
      autoPBSCT. 39 patients with lymphoma or multiple myeloma (MM) received the same
      chemotherapy mobilization regimen, including CTX 400 mg/m2 d1; VLB 2 mg/m(2) d1;
      Ara-C 60 mg/m 2* d1-5; VP-16 60 mg/m2 * d1-5; and prednisone 40 mg/m2 * d1-5. The
      historical control group (12 cases) received G-CSF subcutaneously (filgrastim) at
      the first restoration after the initial nadir of the peripheral WBC count. The
      experimental group (27 cases) received G-CSF during the steady rise of the WBC
      count (end of fluctuating after initial nadir). G-CSF was given in a single daily
      subcutaneous dose of 5 ug/kg until the final PBSC apheresis. When the peripheral
      WBC and mononuclear cell (MNC) counts reached 10 * 109/L and 1.0 * 109/L
      respectively, leukapheresis was carried out using the COBE Spectra blood cell
      separator. The results indicated that despite there was comparable treatment with
      alkylating agents between 2 groups, a significantly increased yield of CD34
      positive cells was observed in the experimental group (26.4 * 106/kg), as
      compared to the historical control group (3.1 * 106/kg) (p = 0.0031). It is
      concluded that the appropriate timing for the use G-CSF mobilization after
      chemotherapy is important to increase the CD34(+) cell yield in auto-graft.

PMID- 21729567
TI  - [Effects of loaded buffer with epigallocatechin gallate on physiological
      functions of platelets].
AB  - This study was aimed to explore the change of aggregation and activation of
      platelets loaded with epigallocatechin gallate (EGCG). The platelets were treated
      by loading buffer with different concentrations of EGCG (0, 2.5, 5, 7.5, 10,
      12.5, 15, 20 and 30 mmol/L) and were divided into 2.5, 5, 10 mmol/L groups and
      control group. The physiological and biochemical functions of platelets were
      observed, including recovery rate, aggregation and activation of platelets. The
      platelet counts were determined by Counter Cell-DYN 1200. The aggregation
      activities were tested through turbidimetry, the platelet apoptosis was detected
      by flow cytometry. The results showed that the concentrations of EGCG loading in
      platelets of 2.5, 5 and 10 mmol/L groups were 0.4006 +/- 0.12, 1.0527 +/- 0.1503,
      1.6902 +/- 0.1112 mmol/L respectively. Along with the increasing of EGCG
      concentrations in loading-buffer, the EGCG absorbed by platelets increased too.
      When the concentration of EGCG in loading-buffer exceeded 15 mmol/L, the EGCG
      absorbed by platelets did not increase. The recovery rate in 2.5 mmol/L loading
      buffer group was 82.45 +/- 0.360% which was lower than that in control group
      (90.33 +/- 1.115%) (p < 0.05). As compared with control group, the recovery rate
      in 5 mmol/L loading buffer group (57.51 +/- 2.468)% and 10 mmol/L loading buffer
      group (47.45 +/- 2.030)% were even significantly lower (p < 0.01). When ADP was
      used as the inducer, the maximal aggregation rate (MAR) in control group was
      (63.6 +/- 4.037)%, which was higher than that in other EGCG-loading groups (p <
      0.01). And the aggregation activity of platelets negatively correlated with the
      concentration of EGCG in loading-buffer. When THR was used as the inducer, the
      MAR in control group was (89.3 +/- 6.533)% and higher than that those in other
      groups (p < 0.05), especially in groups with loading-buffer higher than 10 mmol/L
      EGCG (70.1 +/- 5.400%) (p < 0.01). In the experiment of cellular apoptosis, the
      early apoptosis easy appeared in platelets loaded with EGCG. It is concluded that
      the EGCG loading in platelets markedly influences the physiological and
      biochemical functions of platelets, the apoptosis easy occurs in platelets loaded
      with EGCG. The EGCG accelerates the course of platelet apoptosis.

PMID- 21729568
TI  - [1059 g/c gene polymorphism of C-reactive protein in patients with deep vein
      thrombosis].
AB  - This study was aimed to investigate the distribution of 1059 G/C gene
      polymorphism of C-reactive protein(CRP) in deep vein thrombus (DVT) and its
      clinical significance. Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was used to screen 1059 G/C polymorphism in exon 2 of C
      reactive protein gene in 61 cases of DVT and 60 healthy controls. The frequency
      of mutation was calculated. The results showed that there was no statistical
      difference of 1059 G/C genotype and mutation frequency of allele between deep
      vein thrombosis group and control group (p > 0.05). It is concluded that the 1059
      G/C gene polymorphism of CRP displays certain difference in races and areas, and
      whether 1059 G/C gene polymorphism of CRP is a dangerous factor for deep vein
      thrombosis, which needs to be deeply explored.

PMID- 21729569
TI  - [Healing effect of lyophilized platelets on rat chronic wound model].
AB  - Platelets carry over 20 growth factors, which all have been shown to improve
      wound healing, particularly recalcitrant wound healing. The aim of this study was
      to investigate the healing effect of lyophilized platelets on the chronic wounds
      through establishing diabetic rat chronic wound model. Healthy male SD rats were
      intraperitoneally injected with streptozotocin (STZ) solution at the dose of 65
      mg/kg. The blood glucose and weights were observed every week. The re
      epithelialization rates of normal control group (NDR), diabetic group (DR) and
      diabetic treatment group (TLP) was analysed. Two full thickness skin wounds were
      incised in the back of the rats. The re-epithelialization rates were observed at
      1, 3, 5, 7 and 12 days. The results showed that after induced by streptozotocin
      for 72 hours, the blood glucose of the DR group was higher than 16.7 mmol/L. 1
      week after induced by STZ, the weight of the DR group was significant lighter
      than that of the NDR group (p < 0.05). The re-epithelialization rate of DR group
      were lower than that of NDR. After 12 day treatment, the re-epithelialization
      rates of NDR and TLP groups were 88.1% and 81.8%, which were significantly higher
      than that of DR group (62.8%). It is concluded that diabetic rat model
      established by the intraperitoneal injection of streptozotocin can be used as a
      better diabetic chronic wound model. And the lyophilized platelets have healing
      effect on diabetic chronic wounds.

PMID- 21729570
TI  - [Analysis of vWF gene A1381T polymorphism in patients with coronary heart
      disease].
AB  - This study was purposed to investigate the vWF gene A1381T polymorphism in
      patients with coronary heart disease (CHD). A case-control study was designed,
      including 104 continuously hospitalized patients with CHD, aging from 40 to 75
      years (average 59) and 96 persons underwent physical examination in outpatient
      department as controls, aging from 39 to 70 years (average 56). The plasma vWF:
      Ag level of CHD patients and control persons was detected by ILISA. vWF gene
      A1381T polymorphism was analyzed by the polymerase chain reaction-restriction
      fragment length polymorphism and sequencing when it is necessary. The data were
      grouped by gender, blood group and/or genotype in CHD group and control groups.
      The difference of plasma vWF level between male and female was analyzed by
      independent sample t test; one way ANOVA was used to analyze the difference of
      vWF level between different blood group genotypes, while the factorial design
      ANOVA was used to test the difference of vWF level in plasma between A1381T
      genotype and/or ABO blood groups. chi(2) Crosstabs were used to test the CHD
      susceptibility. The results showed that the frequencies of GG genotype (wild
      type) of vWF gene A1381T polymorphism were 62.5% in CHD group and 67.7% in
      control group, and the frequencies of AG genotype (heterozygous variant) were
      37.5% in CHD group and 32.3% in control group. chi(2) Crosstabs showed no
      significant correlation between vWF gene A1381T polymorphism (AG) and CHD (OR =
      1.258, 95% CI = 0.702 - 2.255, chi(2) = 0.595, p = 0.440). The plasma vWF level
      in CHD group was statistically very higher than that in control group (p <
      0.001), even though the relationship of vWF A1381T polymorphism (rs216311) and
      susceptibility of CHD in CHD group was not found. The plasma vWF level of AG or
      GG genotype was higher in CHD group than in control group (p < 0.001). The plasma
      vWF level of AG genotype was higher than that of GG in CHD group (p < 0.05), but
      not in control group. The plasma vWF of O blood group was lower than that of A, B
      and AB blood groups (p < 0.05), while among A, B, AB blood groups, the vWF level
      was not different (p > 0.05). Among O, A, B, AB blood groups in CHD group, vWF
      level was not different (p > 0.05). Although the two-way analysis of variance
      ANOVA showed no interaction of A1381T genotype and ABO blood groups on plasma vWF
      level, the plasma vWF level in AG mutant of vWF A1381T gene polymorphism with O
      blood group was higher than that of GG mutant (p = 0.023) in CHD group, not
      different in other blood groups. It is concluded that there is no association
      between vWF gene A1381T polymorphism and CHD susceptibility. The plasma vWF level
      in CHD group interrelated with ABO blood group and A1381T polymorphism, in which
      the plasma vWF level in AG genotype increase mostly. Plasma vWF level in vWF gene
      A1381T polymorphism with AG mutant was significantly much higher than GG mutant
      in CHD. This change may be beneficial to further study the effect of A1381T
      polymorphism on vWF gene expression and activity.

PMID- 21729571
TI  - [Therapy of aplastic anemia with autologous peripheral mononuclear cells treated
      by IL-2 and GM-CSF in culture: a long-term follow-up report on 49 patients].
AB  - This study was purposed to evaluate the long-term outcome and the safety of
      autologous peripheral blood mononuclear cells (PBMNC) treated by interleukin 2
      (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) in the
      therapy of patients with aplastic anemia (AA). The therapy of 49 patients
      admitted BG in hospital from April 2001 to December 2007 were analyzed
      retrospectively. PBMNC were isolated and cultured for 48 hours in presence of IL
      2 and GM-CSF. Cells were collected, and 6 * 10(6) - 1 * 10(8) PBMNC were
      intravenously injected weekly for 4 - 22 months. Hematopoietic recovery was
      evaluated by examinations of peripheral blood, bone marrow aspirates and bone
      marrow biopsy. Flow cytometry was used to assess the peripheral T cell subsets
      before and after treatment. Polymerase chain reaction was performed to observe
      the clonal diversity of T cell receptor variable beta-chain (TCR-Vbeta)
      recombination. The results showed that 37 cases were cured and none of them
      relapsed during the follow-up, 5 cases were in partial remission, 3 cases got
      improvement, and 4 cases showed no response. The total efficiency reached up to
      91.8%. The ratios of CD4(+)/CD8(+) subsets were abnormal in 39 patients prior to
      the treatment, and 31 cases restored to the normal range after cell transfusions.
      Analysis on the clonal diversity of TCR-Vbeta recombination in 11 patients showed
      the transition from monoclonal or biclonal spectratype to polyclonal one. No long
      term side effects were documented. It is concluded that the treatment with PBMNC
      treated by IL-2 and GM-CSF is generally safe and effective. The underlying
      mechanisms may be in relation to the restoration of cell immunity.

PMID- 21729572
TI  - [Clinical study of autologous cytokine induced killer cell infusion treating for
      elderly patients with myelodysplastic syndrome].
AB  - Objective of this study was to evaluate the effectiveness and safety of
      autologous cytokine induced killer (CIK) cells combined with IL-2 in treatment of
      elderly patients with myelodysplastic syndromes (MDS). Peripheral blood
      mononuclear cells were isolated from 6 elderly MDS patients and were stimulated
      by cytokines in vitro to form CIK cells. The autologous CIK cells were then
      infused back into the corresponding patients. The regimen was repeated every 4
      weeks. Effector cell proportion changes, adverse effects, effects on
      inflammation, hemoglobin level and blood transfusion were assessed after
      treatment. The results showed that after autologous CIK cell infusion, the
      percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (p
      < 0.05). No severe adverse effects were observed in all patients. It also
      significantly reduced inflammation frequency and shortened high fever duration.
      During stable stage of disease, the CIK cell infusion could reduce the red blood
      cell infusion amount and stabilize hemoglobin level. However, the natural course
      of transformation from myelodysplastic syndromes to high-risk subtypes could not
      be changed by CIK cell treatment. It is concluded that the autologous CIK cell
      infusion is a safe and effective therapy for geriatric myelodysplastic syndrome.

PMID- 21729573
TI  - [114 children with acquired non-severe aplastic anemia benefitted from androgen].
AB  - This study was purposed to assess the efficacy of stanozolol for treatment of
      childhood patients with acquired non-severe aplastic anemia (NSAA). The records
      of 114 children with acquired NSAA treated in hospital between January 1996 and
      January 2009 were analyzed retrospectively. All patients received stanozolol with
      the dose of 0.1 mg/(kg.d). Some patients were treated with supportive care. The
      incidence and the risk factors of progression severe aplastic anemia (SAA)
      including gender, age, absolute neutrophil count, absolute reticulocyte count,
      dependent or independent of transfusion, the ratio of granulocytes and
      erythrocytes were evaluated. The results indicated that at a median follow-up of
      52 months (range 5 - 181), 6 patients (5.3%) progressed into SAA, 93 (81.6%)
      remained in NSAA, and 15 (13.2%) had complete remission. Patients with dependent
      of transfusion (platelet count < 10 * 10(9)/L and/or haemoglobin < 70 g/L) have
      higher risk to progress into SAA (19.2% vs 1.1%) (p = 0.016); patients with lower
      absolute neutrophil count (ANC) (< 0.8 * 10(9)/L) or with lower absolute
      reticulocyte count (ARC) (< 40 * 10(9)/L) at diagnosis have higher risk to
      progress into SAA (8.1% vs 0%) (p = 0.029); (9.1% vs 1.7%) (p = 0.034); Those
      patients with lower ANC (ANC < 0.8 * 10(9)/L) and lower ARC (ARC < 40 * 10(9)/L)
      have higher risk into progress to SAA (19.2% vs 1.1%) (p = 0.016). It is
      concluded that NSAA patients treated with Stanozolol progress into SAA with the
      rate of 5.3%. Those patients with dependent of transfusion or ANC < 0.8 * 10(9)/L
      or/and ARC < 40 * 10(9)/L have higher risk of progress into SAA.

PMID- 21729574
TI  - [Correlation of killer immunoglobulin-like receptor gene diversity with
      nasopharyngeal carcinoma in Chinese southern Han population].
AB  - The objective of this study was to elucidate the correlation of killer
      immunoglobulin-like receptor (KIR) gene diversity with nasopharyngeal carcinoma
      (NPC) in the Chinese southern Han population. KIR genotyping of peripheral blood
      samples from 67 patients with NPC and 77 randomly-selected healthy controls was
      performed by PCR-SSP, the relative risk (RR) value was calculated by means of
      Wolf method. The results showed that the KIR2DL3 gene frequency in NPC patient
      group was significantly lower than that in healthy controls (chi2>3.84, p < 0.05,
      RR = 0.08), whereas the KIR2DS5 and KIR2DL5B gene frequencies in patient group
      were significantly higher than those in healthy controls (chi2>3.84, p < 0.05, RR
      > 1), the other KIR gene frequencies were no statistically different between two
      groups. It is concluded that the KIR2DL3, KIR2DS5 and KIR2DL5B genes may be
      correlated with pathogenesis of NPC in the Chinese southern Han population.

PMID- 21729575
TI  - [Effect of ABO-incompatible allogeneic stem cell transplantation on erythroid
      lineage hematopoiesis].
AB  - This study was purposed to investigate the effect of ABO-incompatible allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) on erythroid lineage
      hematopoiesis. The changes of ABO group, IgM and IgG antibody in 16 patients
      received ABO-incompatible allo-HSCT were detected. The results showed that ABO
      incompatible allo-HSCT were successfully engrafted in 16 patients, and there was
      no difference in reconstitution of platelets and neutrophils between ABO
      incompatible and ABO-compatible transplantation (p > 0.05). The time of erythroid
      lineage reconstitution was prolonged (p < 0.05), the disappearance time of
      isoagglutinins against donor-type RBC in major and bidirectional ABO-incompatible
      recipients was correlated with the time of erythroid lineage reconstitution. It
      is concluded that ABO-incompatible allo-HSCT may lead to prolong recovery of
      erythroid lineage hematopoiesis. Before transplantation, the removal of anti
      donor isoagglutinins by plasmapheresis or transfusion of donor's erythrocytes for
      neutralizing the isoagglutinins against donor's erythrocytes in the recipients
      may facilitate RBC engraftment and reduce erythrocyte transfusion.

PMID- 21729576
TI  - [Expression of radioresistant genes survivin and HO-1 in mesenchymal stem cells].
AB  - This study was aimed to investigate the expression of radioresistant genes
      survivin and HO-1 in mesenchymal stem cells (MSC). Human bone marrow MSC were
      isolated and enriched by Fircoll density gradient centrifugation, then identified
      by flow cytometry. MSC were induced with dexamethasone, insulin, 3-isobutyl-1
      methyl-xanthine (IBMX) and indomethacin to differentiate into adipocytes. Then
      the expression of survivin and HO-1 in MSC was detected by RT-PCR. The results
      indicated that the expressions of surface antigen CD34 and HLA-DR in MSC in vitro
      were negative while the expressions of CD44 and CD71 were positive. MSC could be
      differentiated into adipocytes by inductor. RT-PCR showed the expression of
      radioresistant genes survivin and HO-1 in MSC. It is concluded that MSC have
      lower sensitivity to radiation, which may associate with the expression of
      radioresistant genes survivin and HO-1 in MSC.

PMID- 21729577
TI  - [Role of G-CSF in the proliferation, differentiation and cell cycle distribution
      of mouse thymocytes after acute radiation].
AB  - This study was purposed to investigate the effect of G-CSF on the proliferation,
      differentiation, and cell cycle distribution of thymocytes in sublethally
      irradiated mice. Female BALB/c mice were exposed to 6.0 Gy gamma-ray irradiation
      and then randomly divided into control and G-CSF treatment group. In the
      treatment group rhG-CSF 100 ug/(kg.d) was given subcutaneously for 14 continuous
      days and to make sure the first injection was given within 1 hour after
      irradiation. Cell cycle distribution and apoptosis of thymocytes were detected
      within 72 hours after irradiation. Subpopulations of CD4(-)CD8(-) cells and
      sequential changes in the distribution of CD4(+)CD8(+), CD8(+)CD4(-), CD8(
      )CD4(+) cells were detected by a three-color flow cytometry during a four-weeks
      period after irradiation. The results showed that in G-CSF treatment group marked
      increase of cells in G(0)/G(1) phase (G-CSF vs control: 82.0 +/- 5.0% vs 75.9 +/-
      2.8%) (p < 0.05) and a decrease of cells in S phase (G-CSF vs control: 10.2 +/-
      4.8% vs 15.7 +/- 2.3%) (p < 0.05)could be observed as early as 6 hours after
      irradiation, but G-CSF seems have no evident effects on the cells in G(2)/M
      phase. G-CSF could also protect thymocytes against apoptosis. 6 and 12 hours
      after irradiation the apoptosis rates of thymic cells in G-CSF treatment group
      were 11.5 +/- 2.4% and 15.5 +/- 3.3% respectively, while in the control group the
      apoptosis rates were 16.5 +/- 2.2% and 22.6 +/- 0.7% respectively. Comparison
      between the two group demonstrated significant difference (p < 0.05). CD4(-)CD8(
      ) double negative thymocytes (DN)can be defined as DN1-4 according to their
      maturation. G-CSF treatment resulted in a significant increase in DN1 thymocytes
      and promoted their proliferation and differentiation to a more mature DN3 and DN4
      stage. G-CSF could enhance the recovery of CD4(+)CD8(+) thymocytes and mitigate
      their relapse during reconstitution. The percentage of CD4(+)CD8(+) thymocytes in
      the G-CSF treatment group 28 days after irradiation was significantly higher than
      that of the control group (71.0 +/- 6.3% vs 25.5 +/- 6.3%) (p < 0.05). It is
      concluded that G-CSF has a positive effects on the thymic cell cycle
      distribution, proliferation and differentiation, which may contribute to the
      reconstitution of central immune system after acute irradiation.

PMID- 21729578
TI  - [Research advance on universal red blood cell engineering].
AB  - The preparation and application of universal group O donor red blood cells (RBC)
      are a trend of future transfusion medicine. This article reviewed the
      technologies for producing universal RBC in recent years. One of them is
      modification of blood group antigens, which includes two basic methods. One of
      these two methods is enzymatic cleavage of the terminal immunodominant sugars
      from carbohydrate chains on the membrane of group A or/and group B RBC, in order
      to produce so-called enzyme-converted group O (ECO) RBC. ECO RBC have been
      produced from whole units of B RBC, which then survived normally when given to
      type A and O individuals in clinical trial. Because of the complexity of group A
      antigens, conversion of group A RBC (especially A1 RBC) to group O RBC is more
      difficult. Recently, a new bacterial glycosidase efficiently cleaving antigens on
      the surface of both A1 and A2 RBC has been obtained. Another method is
      pegylation, which camouflage the antigens on the surface of RBC with non
      immunogenic molecules such as polyethylene glycol (PEG) in a non-specific way, to
      provide O, minor antigen negative phenotype RBC. The second technology is
      generating universal RBC from stem cells (such as hematopoietic stem cells, human
      embryonic stem cells) and human dermal fibroblasts, which will provide a new
      resource for blood supply. Great progress has been made, but a number of
      challenges still remain for using them in clinical transfusion, including scale
      up, effectiveness and safety of prepared RBC. However, these researches will
      provide solutions for the problems in current transfusion, such as blood supply
      shortage, blood borne disease and emergency blood transfusion, and enhance the
      safety of clinical transfusions in the near future.

PMID- 21729579
TI  - [Progress of study on the transcription factor SALL4].
AB  - SAL-like 4 (SALL4) locating at chromosome 20q13.13-13.2 encodes a newly
      identified transcription factor containing 8 zinc finger motif. Recent studies
      have revealed the important role of SALL4 gene in the regulation of early
      embryonic development, organogenesis, and proliferation and pluripotency of
      embryonic stem cells. The heterozygous mutations of SALL4 in different loci,
      causing nonsense mutation or frameshift mutation, and resulting in genesis of
      premature terminal codon, are correlated with autosomal dominant hereditary
      diseases such as Okihiro syndrome, acro-renal-ocular syndrome and IVIC syndrome.
      The level of SALL4 expression is increased in germ cell tumors, hepatoid gastric
      carcinoma, acute myeloid leukemia, B-precursor cell leukemia/lymphoma and
      myelodysplastic syndrome. This review focuses on the structure and function of
      SALL4 gene as well as its relevance to related diseases.

PMID- 21729580
TI  - [Veto T cells enhance engraftment allogeneic hematopoietic stem cells].
AB  - Veto activity was defined as the capacity of specifically downregulating
      cytotoxic T-precursor cell (CTL-p) directed against antigens of the veto cells
      themselves but not against third-party antigens. Many studies have shown that the
      most potent veto cells are CD8(+) cytotoxic T lymphocytes (CD8(+)CTLs).
      Effectively, CD8(+)CTLs of donor origin can facilitate engraftment of donor's
      stem cells by eliminating host-alloreactive T lymphocytes. In this article,
      effect mechanisms, depletion of GVH ex vivo, application in vivo, synergistic
      enhancement with rapamycin and regulatory T cells, and anti-tumor effect in the
      hematopoietic stem cell transplantation are summarized.

PMID- 21729581
TI  - [New advance of research on therapy of severe acute radiation sickness with
      mesenchymal stem cells].
AB  - Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells
      with self-renewal and multilineage differentiation potential, which have special
      biological characteristics, such as secreting various cytokines, promoting
      hematopoiesis, accelerating stem cells homing and reconstructing hematopoietic
      microenvironment. MSC are collected and amplified easily, and can be transfected
      by exogenous gene. Many reports indicated that MSC were applied in therapy for
      variety of tissues and organs injury, meanwhile the treatment for acute radiation
      sickness has made significant progress. In this review, the biological
      characteristics and new research advance on MSC in treatment of severe acute
      radiation sickness are summarized and discussed.

PMID- 21729582
TI  - [Some research progress of CXCR4 antagonist AMD3100].
AB  - AMD3100 (Plerixafor) is an antagonist of CXCR4, receptor for stromal cell-derived
      factor-1 (SDF-1).It disrupts binding of SDF-1 to CXCR4 by competing binding site,
      thus blocking the physiological function of SDF-1/CXCR4 axis. SDF-1/CXCR4 axis
      has been shown to play critical roles in stem cell mobilization, migration and
      homing, and in immunoregulation, inflammatory disease, autoimmune disorder,
      embryonic development, and tumor cell proliferation, migration and location.
      AMD3100 has been confined effective for the mobilization of HSC and MSC,
      inhibition of carcinoma growth and metastasis, suppression of some inflammatory
      and autoimmune disorder. Therefore, further research on AMD3100 will be helpful
      to understand the effects of bone marrow microenvironment on the pathogenesis of
      neoplasm, and to restore the traumatic tissues by mobilizing HSC effectively,
      that might provide a new idea and measure for the treatment of certain neoplasms.
      Some research progress of basic research and application on AMD3100 are
      summarized in this review.

PMID- 21729583
TI  - [Research advance of p53 gene in mantle cell lymphoma].
AB  - Mantle cell lymphoma(MCL) is an independent uncommon subtype of B-cell non
      Hodgkin's lymphoma (NHL) according to World Health Organization classification of
      hematopoietic and lymphoid tissue tumors. The genetic hallmark of MCL is the
      chromosomal translocation t(11;14)(q13;q32) that leads to upregulation of cyclin
      D1, an important regulator of the G(1) phase in the cell cycle. This genetic
      aberration is virtually present in all cases of MCL. It is characterized by
      distinct clinical features and outcome which is affected by a series of
      additional genetic aberration including the genomic guardian-P53 gene. This
      article reviews the effects of P53 gene aberrations including P53 deletion,
      mutation and their mutual relationship in MCL, and novel therapeutic regimens for
      MCL patients with P53 aberrations.

PMID- 21729584
TI  - [Advance of clinical study on immune thrombocytopenia caused by irregular
      antibodies].
AB  - The platelet antibodies mainly include platelet-specific and related antibodies,
      which belong to irregular antibodies. They are produced by autoimmune, drug
      induced or isoimmunization (such as pregnancy, blood transfusion and so on), the
      irregular IgG and/or IgM antibodies produce and lead to platelet transfusion
      refractoriness (PTR), post-transfusion purpura (PTP) and isoimmune neonatal
      thrombocytopenic purpura (INTP), idiopathic thrombocytopenic purpura and so on.
      It is very necessary to screen and identify the irregular antibodies before blood
      transfusion or parturition. Except some serological detections should be done
      first, flow cytometry and molecular biological techniques such as PCR and PCR-SSP
      are applied to detect the difficult-matching patients' genotypes and fetal
      genotypes in order to further predict fetal INTP and to provide the right blood
      for difficult-matching patients, therefore, some measures must be taken early for
      prevention and treatment of immune thrombocytopenic purpura. In this review, the
      production, typing and laboratory tests of irregular antibodies, as well as the
      pathogenesis and clinical symptoms of diseases caused by irregular antibodies,
      and the current progress are summarized.

PMID- 21729585
TI  - [Research progress of tumor microenvironment and non-Hodgkin's lymphomas].
AB  - Non-Hodgkin's lymphoma cells including lymphoma stem cells reside in a specific
      microenvironment in which a series of nonmalignant bystander cells and cytokines
      play a crucial role in the genesis and development of non-Hodgkin's lymphomas. In
      addition, tumor microenvironment has important prognostic significance in Non
      Hodgkin's lymphomas. Blocking the cross-talk between the tumor microenvironment
      and lymphoma cells may thus represent a promising new strategy for treating Non
      Hodgkin's lymphomas. This review summarizes the current advance in studies of the
      tumor microenvironment and non-Hodgkin's lymphomas, including cells in tumor
      microenvironment, role of mesenchymal stem cells and stromal cells, auxiliary
      role of T cell subsets, macrcphage and dentritic cells, cytokines, immune
      surveillance and so on.

PMID- 21729586
TI  - [Recent research advance on bone marrow microenvironment-mediated leukemia drug
      resistant mechanism].
AB  - The bone marrow microenvironment consists of bone marrow stromal cells,
      osteoblasts and osteoclasts which facilities the survival, differentiation and
      proliferation of hematopoietic cells through secreting soluble factors and
      extracellular matrix proteins that mediate these functions. This environment not
      only supports the growth of normal and malignant hematopoietic cells, but also
      protects them against the damage from chemotherapeutic agents through the
      secretion of soluble cytokines, cell adhesion, up-regulation of resistant genes
      and changes of cell cycle. In this review, the research advances on drug
      resistance mechanisms mediated by bone marrow microenvironment are summarized
      briefly, including soluble factors mediating drug resistance, intercellular
      adhesion inducing drug resistance, up-regulation of some drug resistance genes,
      regulation in metabolism of leukemic cells, changes in cell cycles of tumor cells
      and so on.

PMID- 21729587
TI  - The XXI Ottorino Rossi award "new series": the founders of neurology.

PMID- 21729588
TI  - Italian neurology: past, present and future.
AB  - This short history of the Italian Society of Neurology focuses on its founders
      and leading personalities. The article also considers the present and the future
      of Italian neurology, emphasising in particular the scientific impact of Italian
      neurological research on the main international journals and the activities
      undertaken to increase the role of neurologists.

PMID- 21729589
TI  - The Italian neurological schools of the twentieth century.
AB  - This lecture is not a historical lecture, but rather a journey through the
      "story" of neurology in Italy from its "prehistoric" beginning in the 19th
      century. The birth of a neurological school is that magical moment in which a
      founder attracts disciples: the more capable this founder is of transmitting
      methodology and allowing his pupils intellectual freedom, the longer his memory
      will live on. On the basis of this idea, the scientific biography of a few
      leading Italian neurologists of the 20th century is outlined, starting from
      Leonardo Bianchi, founder of the Italian Neurological Society in 1907.

PMID- 21729590
TI  - Cerebrovascular diseases at the C. Mondino National Institute of Neurology: from
      Ottorino Rossi to the present day.
AB  - This paper traces the development of research and healthcare models in the field
      of cerebrovascular disorders at the C. Mondino National Institute of Neurology in
      Pavia, Italy. It starts with a description of the original experiences of
      Ottorino Rossi and his thesis on atherosclerosis which date back to the beginning
      of the last century; it then illustrates the connections between his seminal
      essay and the future directions followed by research in this institute, through
      to the development of one of the first stroke units in Italy. In this context, we
      examine a large range of scientific approaches, many related to cerebrovascular
      diseases (such as headaches) and autonomic disorders, and some of their
      biological and physiological markers. The originality of an approach also based
      on tools of advanced technology, including information technology, is emphasised,
      as is the importance of passion and perseverance in the pursuit of extraordinary
      results in what is an extremely complex and difficult field.

PMID- 21729591
TI  - Cesare Lombroso: an anthropologist between evolution and degeneration.
AB  - Cesare Lombroso (1835-1909) was a prominent Italian medical doctor and
      intellectual in the second half of the nineteenth century. He became world famous
      for his theory that criminality, madness and genius were all sides of the same
      psychobiological condition: an expression of degeneration, a sort of regression
      along the phylogenetic scale, and an arrest at an early stage of evolution.
      Degeneration affected criminals especially, in particular the "born delinquent"
      whose development had stopped at an early stage, making them the most "atavistic"
      types of human being. Lombroso also advocated the theory that genius was closely
      linked with madness. A man of genius was a degenerate, an example of retrograde
      evolution in whom madness was a form of "biological compensation" for excessive
      intellectual development. To confirm this theory, in August 1897, Lombroso, while
      attending the Twelfth International Medical Congress in Moscow, decided to meet
      the great Russian writer Lev Tolstoy in order to directly verify, in him, his
      theory of degeneration in the genius. Lombroso's anthropological ideas fuelled a
      heated debate on the biological determinism of human behaviour.

PMID- 21729592
TI  - The effects of alcohol on cognition in the elderly: from protection to
      neurodegeneration.
AB  - The effects of chronic alcohol abuse on cognition are well known. Memory and
      executive functions appear to be the cognitive domains primarily impaired, and
      prefrontal and frontal damage is reported on neuroimaging studies both at micro-
      and macrostructural levels. Abstinence can partially reverse these alterations
      through mechanisms of neuroplasticity. Alcohol acts in a dose-dependent fashion,
      and a light-to-moderate consumption indeed has protective effects on
      cardiovascular risk factors and promotes anti-inflammatory and anti-oxidative
      processes. In the elderly on such a regimen, several epidemiological studies have
      reported a decreased risk of both coronary and cerebrovascular disease and of
      dementia. However, because of data heterogeneity and the presence of several
      confounding variables, further studies are needed to clarify these findings. In
      addition, the complexity of alcohol neurobiology (interaction of alcohol effects
      with genetic predisposition and environmental factors) and the occurrence of age
      related changes should also be taken into account. As dementia, stroke and
      cardiovascular disease are the leading causes of mortality in older people in
      developed countries, a better knowledge of the mechanisms underlying the effects
      of alcohol intake may be helpful from the perspective not only of medical
      management but also of social health policy.

PMID- 21729594
TI  - [Disruption of blood brain-barrier by leukemic cells in central nervous system
      leukemia].
AB  - OBJECTIVE: To observe the effect of leukemic cells on blood-brain barrier (BBB)
      in mice with central nervous system leukemia (CNSL) by establishing mice CNSL
      model and an in vitro BBB model and explore the mechanism of leukemic cell
      infiltrating central nervous system (CNS). METHODS: After splenectomy, cytoxan
      intraperitoneal injection, and sublethal irradiation, 10 BALB/c nu/nu mice were
      transplanted intravenously with 1.2 * 10(7) of SHI-1 human monocytic leukemic
      cells. Mice were monitored for survival and clinical manifestation of nerve
      palsy. The leukemic cells engrafted were examined by RT-PCR, histopathology and
      bone marrow (BM) smears. Immunofluorescence analysis with laser scanning
      fluorescence confocal microscopy was used to determine the expression of
      fibrinogen and tight-junction protein ZO-1. An in vitro BBB model composed of
      human brain microvascular endothelial cells (BMVECs) was developed on a Matrigel
      based insert. Different leukemic cell lines were seeded onto the upper
      compartment of transwell insert. After incubated for 24 h with BMVECs, cells that
      had migrated into the lower compartment were counted and analyzed. RESULTS: (1)
      Paralysis with or without sight loss was developed in half the mice 30-35 d after
      innoculated with SHI-1 cells. Leukemic cells infiltrates were observed in BM and
      in different part of brain tissues including brain parenchyma. The transcriptions
      of human MLL/AF6 fusion gene were also detected in BM and brain tissues in
      paralysis mice. The fibrinogen expression and ZO-1 disruption were detected in
      the infiltrated tissue. (2) After 24 h incubation with leukemic cells, the BMVECs
      sheets were disrupted and grew singly and ZO-1 expression was down-regulated
      markedly. SHI-1 cells showed more injurious to BMVECs and higher invasive rate
      ?[(40.33 +/- 1.53)% vs (11.83 +/- 1.44)%, P < 0.05?] than HL-60 cells did.
      CONCLUSION: One of the mechanisms of leukemic cells infiltrates CNS in CNSL is
      injure to the BBB.

PMID- 21729595
TI  - [Analysis of effectiveness and prognostic factors for (m)HAD regimen as induction
      therapy in acute monocytic leukaemia].
AB  - OBJECTIVE: To analyze the treatment outcome and impact of cytogenetic
      abnormalities on the response and survival of acute monocytic leukaemia (AMOL)
      patients received (m)HAD regimen as induction chemotherapy. METHODS: Seventy-nine
      AMOL patients were treated with (m)HAD regimen as induction therapy (HHT 2
      mg/m(2), d 1-7; Ara-C 100 mg/m(2), d 1-7 and increasing to 1.5 g*m(-2)*(12 h)(
      1), d 5-7 in some patients; DNR 40 mg/m(2), d 1-3). The treatment outcome and
      prognostic factors were analyzed. RESULTS: (1) The complete remission (CR) rate
      was 79.7% (63/79), partial remission (PR) rate was 6.3% (5/79), overall rate was
      86.0%. (2) The chromosome karyotypes were analyzed in 75 patients, of whom 43
      with normal karyotypes (NCR) and 30 abnormal karyotypes (ACR). For the
      cytogenetic prognostic groups, 49 patients were intermediate, 18 poor and 6
      unknown. The CR, 1-year and 3-year overal survival (OS) rates in NCR group were
      significantly higher than those in ACR group (P < 0.05); but there was no
      significantly statistical difference in disease free survival (DFS) between the
      two groups (P > 0.05). The CR, 1-year OS, 3-year OS and 1-year DFS and 3-year DFS
      rates in intermediate prognostic group were significantly higher than those in
      poor prognostic group (85.7% vs 61.1%, 75.9% vs 51.3%, 65.4% vs 25.6%, 82.2% vs
      66.7%, and 77.9% vs 26.7%, respectively) (P < 0.05). (3) Chromosome karyotype and
      the number of consolidation therapy courses had more important influence on
      survival in COX analysis. CONCLUSION: (m)HAD regimen as induction chemotherapy
      for AMOL patients achieves a high CR rate. It has an important influence on
      survival for the patients to received adequate consolidation therapy. The
      frequency of cytogenetic abnormalities in AMOL is similar to that in other AMLs.
      The prognosis of AMOL patients with chromosome karyotype in intermediate
      prognostic group is significantly better than that in poor prognostic group.

PMID- 21729596
TI  - [Relationship between RAD51-G135C/XRCC3-C241T polymorphisms and development of
      acute myeloid leukemia with recurrent chromosome translocation].
AB  - OBJECTIVE: To investigate the relationship between DNA homologous recombination
      (HR) repair genes RAD51-G135C/XRCC3-C241T polymorphisms and development of acute
      myeloid leukemia (AML) with recurrent chromosome translocation. METHODS: Genomic
      DNA was extracted from bone marrow cells of 625 de novo AML patients and
      peripheral blood cells of 806 patient family members and 704 unrelated
      volunteers. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by PCR-RFLP.
      Cell lines with genotypes differed from XRCC3-C241T were selected and irradiated
      in vitro. The CBFbeta-MYH11 fusion gene was detected by TaqMan real-time PCR.
      RESULTS: The XRCC3-C241T variant (C/T + T/T) showed 6.22-fold and 6.99-fold
      increase in the risk of developing the AML with inv(16)/t(16;16)/CBFbeta-MYH11 as
      compared with the volunteer and family member controls respectively; the RAD51
      G135C homozygote-type (C/C) variant showed 0.87-fold (P = 0.010) and 1.15-fold (P
      = 0.001) respectively increase in the risk of this subtype AML. In the irradiated
      group, the CBFbeta-MYH11 mRNA level in HL-60 cells was 59.49 times increased than
      that in KG1a cells. However, the RAD51-G135C and XRCC3-C241T variants had no
      correlations with the risk of development of t(15;17)/PML-RARalpha(+)AML,
      t(8;21)/AML1-ETO(+) AML and 11q23 AML subtypes. CONCLUSION: The XRCC3-C241T
      variant and the RAD51-G135C homozygote-type significantly increase the risk of
      the development of AML with inv(16)/t(16;16)/CBFbeta-MYH11.

PMID- 21729597
TI  - [The incidence of TET2 gene mutation and its clinical significance in acute
      myeloid leukemia patients].
AB  - OBJECTIVE: To evaluate the prevalence of TET2 gene mutation in acute myeloid
      leukemia (AML) patients, and analyze their clinical characteristics and
      prognosis. METHODS: Polymerase chain reaction (PCR) and direct sequencing were
      used to sequence exon 3 to 11 of TET2 gene. RESULTS: Among 96 AML patients, TET2
      gene mutation was detected in 13 (13.54%) patients (95%CI 6.70% - 20.38%). The
      median age was 54 years in mutated group and 41 years in unmutated group (P =
      0.010). Mutated and unmutated patients did not significantly differ in gender,
      white blood cells (WBC) count at diagnosis, platelet count, PB and BM blast
      percentage and chromosome karyotype, excepting for hemoglobin level 84 (70 - 108)
      g/L in mutated group versus 70 (55 - 87) g/L in unmutated group (P = 0.032). TET2
      gene mutation had no significant correlation with C-KIT, FLT3, JAK2V617F
      mutations, but did with NPM1 mutation. TET2 mutated patients had lower CR1 rate
      and 2-year overall survival than unmutated in non-M(3) patients (P < 0.05).
      CONCLUSIONS: TET2 gene mutation is more prevalent in older AML patients and has a
      certain correlation with clinical characteristics and outcome. It may be a
      molecular marker for poor prognosis in AML.

PMID- 21729598
TI  - [Treatment options and prognosis in newly diagnosed multiple myeloma patients].
AB  - OBJECTIVE: To explore the effect of treatment option on the response and outcomes
      in multiple myeloma (MM) patients suitable for autologous hematopoietic stem cell
      transplantation (auto-HSCT). METHODS: A total of 71 newly-diagnosed MM patients
      less than 65 years admitted to RuiJin Hospital from June 2005 to December 2009
      were analyzed retrospectively. Among them, 21 received auto-HSCT (HSCT group)
      with standard conditioning of melphalan 200 mg/m(2), 30 received conventional
      chemotherapy (conventional group) and 20 received Bortezomib-based therapy
      (Bortezomib group). The responses and outcomes of different treatments were
      analyzed. RESULTS: The median follow-up duration for all patients was 18 (1 - 58)
      months with estimated 3-year overall survival (3-yr OS) of (79.8 +/- 6.3)% and
      progression-free survival (3-yr PFS) of (54.8 +/- 9.0)%. Thirty-four patients
      achieved complete remission (CR) or very good partial remission (VGPR) on
      induction therapy, which were 80% for the Bortezomib group, 33.3% for the
      conventional group and 38.3% for the HSCT group. After auto-HSCT the CR + VGPR
      rate was increased to 76.1% for the HSCT group. Overall, the 3-yr PFS was (26.3
      +/- 13.8)% (median 21 months), (40.5 +/- 20.1)% (median 25 months) and (93.8 +/-
      6.1)%(median not reached, P = 0.025) for conventional, Bortezomib and HSCT groups
      respectively. Univariate analysis demonstrated that CR/VGPR after induction (P =
      0.020), best response of CR/VGPR (P < 0.01), autoHSCT (P = 0.002) and maintenance
      therapy after CR/VGPR (P = 0.0005) were associated with improved PFS and that
      CR/VGPR after induction (P = 0.009), best response with CR/VGPR (P < 0.01),
      maintenance therapy for any patients (P = 0.035) and maintenance therapy for
      patients with CR/VGPR (P = 0.031) were associated with OS. In multivariate
      analysis, only auto-HSCT (P = 0.039) and best response of CR/VGPR (P = 0.009)
      were independent prognostic factors for PFS and the best response of CR/VGPR was
      the only independent prognostic factor for OS (P = 0.005). The estimated 3-yr OS
      was (62.4 +/- 13.7)%, (94.1 +/- 5.7)% and (87.9 +/- 8.3)% respectively for 3
      groups. CONCLUSIONS: For newly-diagnosed MM younger than 65 are suitable for auto
      HSCT, the best response of CR/VGPR was associated with OS and PFS. Auto-HSCT is
      also important prognostic factor for PFS. Induction therapy with Bortezomib can
      achieve rapid CR/VGPR while auto-HSCT as a crucial consolidation therapy and
      maintenance therapy maybe also important for improvement of long-term outcome.

PMID- 21729599
TI  - [Study on matrine alleviating retinoic acid resistance in acute promyelocytic
      leukemia].
AB  - OBJECTIVE: To explore the role of matrine (MAT) alleviating all-trans retinoic
      acid (ATRA) resistance in acute promyelocytic leukemia (APL) and its mechanism.
      METHODS: ATRA sensitive strain of APL (NB4) and resistant strain (NB4-R1, NB4-R2)
      were used in this study. The low toxic dosage of MAT was established by MTT test,
      and ATRA IC(50) of the cell strains (cultured with or without 0.1 mmol/L MAT)
      were obtained to confirm the reversal index (RI); the influence of MAT (10, 8, 6,
      4, 2, 1, 0.1, 0.01, 0.001 mmol/L) combine with 1 umol/L ATRA on the
      differentiation of the three cell strains were observed by nitro blue tetrazolium
      chloride (NBT) test and morphologic changes. The apoptosis rate of cells treated
      with different concentration of MAT combined with 1 umol/L ATRA was tested by
      flow cytometry with Annexin V/PI staining. RESULTS: (1) The toxicity of MAT to
      NB4, NB4-R1, and NB4-R2 cells was increased with the concentration, IC(50) value
      was (0.661 +/- 0.035) mmol/L, (0.673 +/- 0.132) mmol/L and (0.329 +/- 0.020)
      mmol/L, respectively; (2) After treated with 0.1 mmol/L MAT, the ATRA resistance
      factor of NB4-R1 decreased markedly (RI = 4.96 +/- 1.15), but did not of NB4
      R2(RI = 0.66 +/- 0.17); (3) The differentiation capacity of NB4 and NB4-R1 was
      enhanced with increase of MAT, and peaked at 0.1 mmol/L (P < 0.05), but did not
      of NB4-R2; (4) After treated with MAT, the ATRA (1 umol/L) induced apoptosis rate
      in NB4 and NB4-R1 increased significantly (P < 0.05 and P < 0.01, respectively).
      CONCLUSION: MAT can reverse the ATRA resistance of NB4-R1, which may relate to
      the effect of MAT on differentiation and apoptosis. Treatment with MAT plus ATRA
      may exaggerate the cells resistance potency.

PMID- 21729600
TI  - [Promoter methylation status of hPer3 gene in AML patients and the in vitro
      effect of decitabine on the status].
AB  - OBJECTIVE: To investigate the clinical significance of promoter methylation
      status of hPer3 gene in acute myeloid leukemia (AML) patients and the in vitro
      effect of decitabine (DCA) on AML cell lines HL-60 and U937. METHODS: The
      promoter methylation status of hPer3 gene and mRNA expression levels in bone
      marrow of 206 AML and 40 iron deficiency anemia (IDA) patients (as control) were
      detected by methylation specific PCR (MS-PCR) and real-time PCR (RT-PCR). The HL
      60 and U937 cell lines were treated with different concentrations of DCA for 48
      and 72 h. The inhibition rates of cell proliferation were detected by methyl
      thiazolyl tetrazolium (MTT); the early apoptosis rates by staining with Annexin V
      and PI; the CD14 and CD11b expressions by flow cytometry (FCM); the promoter
      methylation status of hPer3 gene by MS-PCR; and the hPer3 mRNA expressions levels
      by RT-PCR. RESULTS: The promoter methylation rates of hPer3 in newly diagnosed
      (ND) group, partial remission(PR) group, complete remission (CR) group, relapse
      (R) group and control group were 93.65% (59/63), 54.39% (31/57), 24.66% (18/73),
      61.54% (8/13) and 0% (0/40), and the hPer3 mRNA expression levels were 0.19 +/-
      0.08, 6.28 +/- 2.11, 52.76 +/- 14.17, 8.18 +/- 4.36, 75.03 +/- 18.16,
      respectively. There was a significant statistic difference between any two group
      (P < 0.01) excepting for between PR and R group (P > 0.05). After DCA treatment,
      the promoter hypermethylation status of hPer3 was reduced and the mRNA and CD14,
      CD11b expression levels were up regulated in a dose dependent manner with an
      induction of cell apoptosis. CONCLUSIONS: Promotor methylation status and mRNA
      expression of hPer3 gene may be indicators for evaluating AML. DCA can induce the
      expression of hPer3 gene and cells apoptosis in AML.

PMID- 21729601
TI  - [The role of Th17 cells in early onset of mice acute graft versus host disease].
AB  - OBJECTIVE: To explore the role of Th17 cells in early onset of acute graft-versus
      host disease (aGVHD) and its mechanism. METHODS: Mice aGVHD model was established
      by irradiated BABL/c mice inoculated with mixed suspension of C57BL/6 bone marrow
      cells and splenocytes. The mice were divided into 4 groups: (1) normal control,
      (2) irradiated group, (3) allo-BMT + DMSO group, (4) allo-BMT + halofuginone (HF)
      group. HF was given intraperitoneally at 5 ug per mouse from -1 d to +10 d after
      allogeneic bone marrow transplantation(allo-BMT).Mice aGVHD symptoms and survival
      were observed. Th1/Th17 cells ratio was evaluated by flow cytometry. RESULTS: All
      the experimental groups (3) and (4) developed aGVHD after transplantation. More
      severe aGVHD was observed in group (4) than in group (3). HF prevented cutaneous
      aGVHD in all the mice, but augmented hepatic and small intestine GVHD. The
      percentage of Th17 cells and the ratio of Th1/Th17 were significantly higher
      while the percentage of Th1 cells was significantly lower in group (4) at day +6
      (P < 0.05). CONCLUSION: Early blockage of Th17 cell results in increase of Th1
      cell percentage, which exacerbates aGVHD.

PMID- 21729602
TI  - [The effects of stem cell factor on proliferation, transmigration, capillary tube
      formation of endothelial cells and on the chemotaxis of CD133(+) cells].
AB  - OBJECTIVE: To explore the effects of stem cell factor (SCF) on proliferation,
      transmigration, capillary tube formation of human umbilical vein endothelial
      cells (HUVEC) and on the chemotaxis of CD133(+) cells. METHODS: In the presence
      of blank control, SCF, vascular endothelial growth factor (VEGF), anti-human SCF
      (anti-SCF) or human IgG, the difference in proliferation capacity of HUVEC was
      analyzed by MTT and CCK-8 methods, and wound scratch assay and three-dimensional
      in vitro Matrigel assay were used for transmigration and capillary tube formation
      of HUVEC, respectively. In addition, the chemotaxis of CD133(+) cells sorted from
      human umbilical cord blood by flow cytometry was investigated by Transwell
      migration assay. RESULTS: SCF didn't improve the proliferative capacity of HUVEC,
      but significantly enhanced the transmigration capacity, and increased capillary
      tube formation in a dose-dependent manner. The number of intact tubules [(30.0 +/
      3.4)/10(5) HUVEC] formed by HUVECs in the presence of the optimal concentration
      of SCF (100 ng/ml) was remarkably higher than that in blank control group [(5.0
      +/- 2.6)/10(5) HUVEC, P < 0.01]. SCF also significantly induced a chemotactic
      response of CD133(+) cells, the transmembrane migration cell number into
      Transwell lower chamber was significantly higher in SCF group [(118.0 +/-
      6.5)/10(4) CD133(+) cells] than in blank control group [(47.0 +/- 4.7)/10(4)
      CD133(+) cells, P < 0.01 ]. CONCLUSIONS: SCF significantly promotes the
      transmigration and capillary tube formation of HUVEC, and induces a chemotactic
      response of CD133(+) cells. SCF/c-kit signaling possibly plays a critical role in
      regulating angiogenesis of vascular endothelial cells and vasculogenesis of
      endothelial progenitor cells.

PMID- 21729603
TI  - [Clinical and gene study of three pedigrees of phytosterolemia associated with
      macrothrombocytopenia and hemolysis].
AB  - OBJECTIVE: To study the clinical features and ABCG5/ABCG8 gene mutations of three
      pedigrees of phytosterolemia presented with macrothrombocytopenia and hemolysis.
      METHODS: Erythrocyte and platelet morphology were examined under light
      microscope. Plasma sterol levels were measured by high pressure/performance
      liquid chromatography method. All of ABCG5 and ABCG8 exons and intron-exon
      boundaries were directly sequenced to identify mutations, the corresponding gene
      mutation sites of three families members and healthy individuals were detected.
      RESULTS: All the patients presented macrothrombocytopenia, hemolysis,
      splenomegaly and xanthomas. The blood smears showed large platelets, some as
      large as erythrocytes, and abnormal erythrocyte shapes, such as stomatocytes.
      Plasma concentrations of phytosterols, especially sitosterol were markedly
      elevated (30 fold) in the affected patients. Four mutations were identified in
      these three pedigrees, ABCG5 C20896T (R446X) and A20883G, ABCG8 del43683-43724
      and del1938C-1939G/ins1938T. The latter three were novel mutations reported for
      the first time. CONCLUSIONS: Phytosterolemia associated with
      macrothrombocytopenia and hemolysis is a new subtype of this disease. Plasma
      phytosterols and related gene analysis should be performed when ever an
      unexplained macrothrombocytopenia, especially combined with haemolysis or/and
      stomatocytosis.

PMID- 21729604
TI  - [Treatment of one hairy cell leukemia case with single course of cladribine].

PMID- 21729605
TI  - [Expression of vWF73 and VWF114 fragments of von Willebrand factor A2 domain and
      their utilization in detecting ADAMTS13 activity].
AB  - OBJECTIVE: To construct the expression vectors of vWF73 and vWF114 fragments of
      von Willebrand factor (vWF) A2 domain, and to express glutathione S-transferase
      (GST) fusion proteins in E. coli, and to explore their values in measuring
      ADAMTS13 activity as substrates. METHODS: The DNA fragments encoding vWF73 and
      vWF114 were generated using PCR and separately cloned into pGEX-6P-1, a
      Schistosoma japonicum GST fusion expression vector. The expression of GST-vWF73-H
      and GST-vWF114-H was induced in liquid culture, followed by purification with Ni
      NTA agarose column. The cleavage of two GST fusion proteins by recombinant
      ADAMTS13 (rADAMTS13) or plasma from normal individuals and thrombotic
      thrombocytopenic purpura (TTP) patients were identified by Western blot. Based on
      an enzyme-linked immunosorbent assay (ELISA) with anti-GST and anti-His
      monoclonal antibodies, GST-vWF73-H and GST-vWF114-H were used to measure plasma
      ADAMTS13 activity as substrates. RESULTS: Two small molecular substrates of
      ADAMTS13, GST-vWF73-H and GST-vWF114-H, are expressed and purified, which could
      be specifically cleaved by rADAMTS13 or plasma from healthy individuals, but not
      by plasma from congenital or idiopathic TTP patients. An ELISA assay was
      established to detect plasma ADAMTS13 activity using GST-vWF73-H and GST-vWF114-H
      as substrates. CONCLUSIONS: Two GST fusion proteins in vWF A2 domain, vWF73 and
      vWF114, were expressed effectively using a prokaryotic expression system and
      could be used to detect ADAMTS13 activity as substrates.

PMID- 21729606
TI  - [Granulocytic sarcoma of abdomen in an an acute myeloid leukemia patient with
      inv(16) and t(6;17) chromosome abnormalities: a case report and literature
      review].

PMID- 21729607
TI  - [Analysis of idiopathic pneumonia syndrome related risk factors after allogeneic
      hematopoietic stem cell transplantation].

PMID- 21729608
TI  - [Study of relationship between plasmacytoid dendritic cells and minimal residual
      disease in childhood acute lymphoblastic leukemia].

PMID- 21729609
TI  - [Study of transfection of human embryonic stem cell with green fluorescent
      protein mediated by lentiviral vectors].

PMID- 21729610
TI  - [A chronic myeloid leukemia patient with t(9;22;14)(q34;q11;p11) translocation].

PMID- 21729611
TI  - [Progression of sorafenib in the treatment of acute myeloid leukemia].

PMID- 21729612
TI  - [Progression of relationship between mesenchymal stem cell and immunoregulation].

PMID- 21729613
TI  - [Several discussions about expert consensus on diagnosis and treatment of
      aplastic anemia].

PMID- 21729614
TI  - [With firm strides we are crossing its summit].

PMID- 21729615
TI  - [General and interventional treatment of bronchial tuberculosis].

PMID- 21729616
TI  - [Management on complications of fiberoptic bronchoscopy].

PMID- 21729617
TI  - [Interventional management of benign airway stenosis].

PMID- 21729618
TI  - [Application of selective bronchial occlusion for intractable pneumothorax].

PMID- 21729619
TI  - [A pilot study on interventional bronchoscopy in the management of airway
      stenosis with benign hyperplasia].
AB  - OBJECTIVE: To evaluate the efficacy of different interventional bronchoscopic
      techniques for the management of benign cicatricial hyperplasia airway stenosis,
      and to study the factors associated with the treatment effects. METHODS: From
      December 2004 to December 2009, 36 patients with cicatricial airway stenosis were
      admitted to our department. An investigation was made to analyze the effects by
      different interventional bronchoscopic treatments. The most suitable treatment
      modality for cicatricial airway stenosis was explored and described. RESULTS: For
      the 36 patients, the disease was cured in 9, improved in 10, not improved in 12,
      and failure in 5. The cure rate, effective rate and ineffective rate were 25%,
      53% and 47%, respectively. Further analysis showed that the effective rate was 8%
      and 82% respectively for the electrical coagulation therapy and the balloon
      dilation combined with needle electrical knife and/or cryotherapy. Restenosis
      extension after operation occurred in 67% of the cases by electrical coagulation
      therapy, but only 12% of cases by the balloon dilation combined with needle
      electrical knife and/or cryotherapy. CONCLUSIONS: Our experience demonstrated
      that for the treatment of airway cicatricial stenosis, electrical coagulation
      might induce and worsen serious airway restenosis resulting in failure of
      treatment. On the other hand, balloon dilation combined with needle electrical
      knife and/or cryotherapy might be a relative safe and effective therapy for
      airway cicatricial stenosis.

PMID- 21729620
TI  - [Clinical features of pulmonary involvement in patients with microscopic
      polyangiitis].
AB  - OBJECTIVE: To explore the clinical features of pulmonary involvement in patients
      with microscopic polyangiitis (MPA). METHODS: We retrospectively investigated the
      clinical data of 50 patients hospitalized with MPA in Peking Union Medical
      College Hospital from January 2008 to December 2009, the data included clinical
      manifestation, laboratory parameters, echocardiography, pulmonary function test,
      chest computed tomography, and histopathology of kidney. RESULTS: Pulmonary
      involvements were observed in 46 patients, common symptoms include cough (34/46),
      expectoration (30/46), dyspnea (19/46) and hemoptysis (16/46). Pulmonary
      involvement was the initial manifestation in 14 patients, five cases had
      radiographic evidences of usual interstitial pneumonia before MPA was diagnosed.
      The prevalence of positive MPO-ANCA antibodies in MPA patients was 96%. The
      prevalence of positive PR3-ANCA antibodies was 6%. Radiographic manifestations
      included ground glass attenuation (16/37), interstitial changes (16/37),
      infiltrates (12/37) and pleural effusion (7/37). The most frequent abnormality in
      pulmonary function test was reduced carbon monoxide diffusing capacity (12/15)
      and restrictive ventilation dysfunction (4/15). The incidences of pulmonary
      hypertension was 33% (13/39), the average pulmonary artery systolic pressure was
      (48 +/- 8) mm Hg (1 mm Hg = 0.133 kPa). CONCLUSION: The prevalence of pulmonary
      involvement in patients with MPA was high, pulmonary involvement was the initial
      manifestation in 28% patients. The clinical manifestations were nonspecific,
      radiographic manifestations included ground glass attenuation, interstitial
      changes, infiltrates and pleural effusion. The short term prognosis was well in
      patients with pulmonary involvement treated with systemic corticosteroids and
      cyclophosphamide, infection was a leading cause of death in patients with
      pulmonary involvement.

PMID- 21729621
TI  - [Localization of the bronchial air leakage in pneumothorax by injection of human
      albumin foam].
AB  - OBJECTIVE: To evaluate the efficacy and safety of a new method to determine the
      bronchus for air leakage in pneumothorax by injection of human albumin foam.
      METHODS: In 29 cases with pneumothorax, the bronchus responsible for air leakage
      was localized by injecting foam of human albumin into target bronchus under
      direct view of bronchoscopy. RESULTS: The bronchus for air leakage was
      successfully localized in all the 29 cases of pneumothorax. The average time for
      locating (from injection of the foam to the localization of the bronchus) was
      (4.0 +/- 1.2) min, and the average amount of 20% human albumin used was (8.0 +/-
      2.6) ml for each patient. The air leakage was treated accordingly, and occlusion
      by fibrin glue was successfully carried out in 21 cases and by OB glue in 8
      cases. Severe cough was noted in 6, fever in 4, thoracic bleeding in 4 cases, and
      chest pain in 1 case. CONCLUSION: Injection of human albumin foam into target
      bronchus under bronchoscopy was a simple, safe and effective method for the
      localization of the bronchus for air leakage in pneumothorax.

PMID- 21729622
TI  - [Epidemiological characteristics of infection for close contacts of pandemic
      (H1N1) 2009 in Beijing].
AB  - OBJECTIVE: To examine the epidemiological characteristics of infection for close
      contacts of pandemic (H1N1) 2009 and to provide scientific evidence for
      preparedness and response for the next pandemic. METHODS: A total of 613 index
      cases with clear information of close contacts and their 7099 close contacts,
      determined between May 16 and September 15, 2009, were included in this study.
      Based on data of epidemiological investigation, sampling and test of index cases
      and close contacts, the characteristics of infection for close contacts were
      described. RESULTS: 56.8% (348/613) of the index cases were male, and 43.2%
      (265/613) were female, and the median age was 20 years (range: 1 - 75 years).
      49.6% (3518/7099) of the close contacts were male, and 49.5% (3514/7099) were
      female, but the sex information of 0.9% (67/7099) could not be recorded. The
      median age of the close contacts was 27 years (range: 0 - 99 years). 2.4%
      (167/7099) of close contacts were infected. The attack rates decreased with
      increasing age of close contacts (chi()2 = 27.87, P < 0.001), and were
      significantly different between various contact patterns of close contacts
      (chi()2 = 109.76, P < 0.001). 14.4% of the infected close contacts were
      asymptomatic. For close contacts with symptomatic infection, virus could be shed
      4.5 days before illness onset, and the median generation time was 2.4 days.
      CONCLUSION: The attack rate of close contacts was very low; and the attack rates
      were different between various ages and contact patterns of close contacts. In
      this series 14% of cases with pandemic (H1N1) 2009 were asymptomatic. The
      symptomatic cases might have infectivity 1 day earlier before illness onset.

PMID- 21729623
TI  - [An analysis on results of smear and culture of sputum from smear-positive
      tuberculosis patients].
AB  - OBJECTIVE: To study the positive rate of smear and culture in different sputa
      from smear-positive patients with tuberculosis, and to discuss the criteria of
      sputum selection for smear and culture. METHODS: The results of smear and culture
      of sputum samples from 3813 cases during tuberculosis drug-resistance baseline
      survey in 2007 were retrospectively analyzed. The positive rates of smear and
      culture of spot sputum, night sputum and morning sputum were compared, and the
      culture positive rate of sputum samples with 1-2 acid fast bacilli (AFB)/300
      fields was summarized. The chi(2) test was used for comparison. RESULTS: The
      smear positive rate of spot sputum, night sputum, and morning sputum was 75.2%
      (2868/3813), 87.9% (3350/3813), and 89.4% (3408/3813) respectively. The
      percentage of cases which were positive for all the 3 sputum samples was 64.5%
      (2460/3813), while that for 2 samples and 1 sample was 23.4% (893/3813) and 12.1%
      (460/3813) respectively. The cumulative smear positive rate of spot sputum plus
      morning sputum reached 96.9% (3695/3813) of the rate combined from the 3 sputum
      samples. The culture positive rate of spot sputum, night sputum, and morning
      sputum was 97.8% (1654/1691), 96.7% (3006/3107) and 97.2% (2473/2543)
      respectively. For the smear positive cases, the positive rate of 2 sputum culture
      increased only 1.7% - 2.8% compared with that of 1 sputum culture. The culture
      positive rate of samples with a smear result of 1 - 2 AFB/300 fields was 90%
      (98/109). CONCLUSIONS: When spot sputum and morning sputum are collected for the
      diagnosis, the number needed for smear can be decreased from 3 to 2. For smear
      positive cases, if sputum is selected for culture according to the smear result,
      the number needed for culture can be decreased from 2 to 1. A smear result of 1 -
      2 AFB/300 fields is of considerable diagnostic value for tuberculosis.

PMID- 21729624
TI  - [A study of double antigen sandwich colloidal gold immunochromatography rapid
      detection for Mycobacterium tuberculosis antibody].
AB  - OBJECTIVE: To establish a simple, fast and accurate double antigen colloidal gold
      immunochromatographic technique for detecting Mycobacterium tuberculosis antibody
      from tuberculosis patients. METHODS: The fusion protein ESAT-6-16-38 was
      constructed by using gene cloning technique for the 6, 16 and 38 kDa early
      secreted antigenic target from Mycobacterium tuberculosis. The ESAT-6-16-38
      fusion protein was marked to colloidal gold to establish the double antigen
      colloidal gold immunochromatographic assay. Serum samples from 163 patients with
      tuberculosis, including 57 sputum-positive cases, 64 sputum-negative cases, and
      42 cases with extrapulmonary tuberculosis, were collected during 2007 and 2009
      from the Disease Prevention and Control Center of Deqing County. In addition, 573
      controls (224 healthy volunteers, 217 patients with acute pneumonia and
      bronchitis, 132 patients with paragonimiasis) were recruited for comparison.
      Mycobacterium tuberculosis specific antibodies were detected by using
      immunochromatographic and protein chip technique. Detection rate was compared
      with Chi-square test. RESULTS: Among the 163 tuberculosis patients, the positive
      rates of immunochromatographic detection and protein chip were 73.0% (120/163)
      and 72.4% (118/163) respectively; the difference was not statistically
      significant (chi()2 = 0.062, P > 0.05). Among the 573 controls, the negative
      rates of immunochromatographic detection and protein chip were 93.9% (538/573)
      and 92.0% (527/573) respectively; the difference was not statistically
      significant (chi()2 = 0.635, P > 0.05). There was no cross reaction in the
      paragonimiasis patients. The positive rate of the immunochromatographic assay was
      as high as 87.7% (50/57) in the sputum-positive patients. CONCLUSIONS: The double
      antigen immunochromatographic technique is an easy to operate, rapid, highly
      sensitive, specific, and reproducible method for the detection of Mycobacterium
      tuberculosis antibodies.

PMID- 21729625
TI  - [A study on the endogenous cannabinoid system synthetic and catabolic enzyme
      levels in patients with obstructive sleep apnea].
AB  - OBJECTIVE: To observe the differences of endogenous cannabinoid system (ECS)
      synthetic and catabolic enzyme levels between the obstructive sleep apnea
      syndrome (OSA) patients and the control subjects. METHODS: Patients with OSA
      confirmed by PSG in our Sleep Center were randomly recruited from July to
      December, 2009. Peripheral blood was obtained to isolate mononuclear cells and
      the mRNA levels of anandamide (AEA) synthase N-acylphosphatidylethanolamine
      hydrolyzing phospholipase D (NAPE), fatty acid amide hydrolase (FAAH) and 2
      arachidonoylglycerol (2-AG) synthase diacylglycerol lipase (DAGL) and hydrolase
      monoacylglycerol lipase (MAGL) were measured by real-time polymerase chain
      reaction. The association between the severity of OSA and the enzyme levels were
      explored. RESULTS: There was a significant difference in both the NAPE and MAGL
      levels between patients with OSA and the control subjects. The level of MAGL was
      related to some indices of severity of OSA, including the longest apnea time,
      lowest blood oxygen saturation and the micro-arousal index (r = 0.31, 0.24, 0.34,
      respectively, all P < 0.05). Compared with patients with OSA alone, patients with
      OSA complicated by hypertension showed a different level of FAAH (P < 0.05).
      CONCLUSION: OSA altered the expression of the ECS synthetic and catabolic
      enzymes, leading to an increase in endogenous cannabinoid substances.

PMID- 21729626
TI  - [Association of leukotriene gene polymorphisms with response to antileukotriene
      treatment in patients with asthma].
AB  - OBJECTIVE: To investigate the frequencies of leukotriene gene single nucleotide
      polymorphisms (SNPs) in the asthmatic subjects of Han population in Wenzhou
      district, and the association between SNPs and response to montelukast treatment.
      METHODS: Sequenom matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) was used to genotype six polymorphisms in 60 asthmatic patients and
      61 controls. According to the SNPs results, 11 cases with the LTC(4)S (rs730012)
      CC + AC genotype and 11subjects with the AA genotype were given montelukast
      treatment, and evaluated by the response of pulmonary function and urinary
      leukotriene E(4). RESULTS: The frequencies of mutant SNPs in ALOX(5) (rs2115819,
      rs4986832, rs4987105), LTA(4)H (rs2660845), ALOX(5)AP (rs10507391) and LTC(4)S
      (rs730012) were less than 50%. There were no statistical differences of the
      haplotype distribution (P values were 0.914, 0.609, 0.609, 0.315, 0.752 and 0.636
      respectively). No statistical differences of the mutant allele frequencies were
      observed in the genes ALOX(5) (rs2115819, rs4986832, rs4987105) and LTA(4)H
      (rs2660845) (OR values were 1.112, 0.964, 0.964 and 0.673 respectively, all P >
      0.05). The invalid value (OR = 1.0) was included in the 95%CI of odds ratios.
      There were no differences of genotype distribution in the above loci (chi(2)
      values were 0.792, 2.684, 2.683 and 2.524 respectively, all P > 0.05). There was
      a statistical difference in the ALOX(5)AP (rs10507391) mutant allele between the
      2 groups, and the frequency of mutant allele A in the asthma group was 23.3% (OR
      = 2.016, 95%CI = 1.027 - 3.959, P < 0.05). There was a statistical difference in
      the LTC(4)S (rs730012) mutant allele between the 2 groups, and the frequency of
      the mutant allele C in the asthma group was 25.0% (OR = 1.926, 95%CI = 1.007 -
      3.685, P < 0.05). Compared with the AA genotype, the LTC(4)S (rs730012) CC + AC
      genotype showed a significant improvement of FEV(1) (t = 6.185, P < 0.01) and
      urinary LTE(4) level (t = 2.925, P < 0.05) after receiving montelukast treatment.
      CONCLUSIONS: These results suggest that the SNPs of ALOX(5)AP (rs10507391) and
      LTC(4)S (rs730012) are associated with asthma in our patients. The LTC(4)S
      (rs730012) locus genetic polymorphism contributes to improvement in montelukast
      response.

PMID- 21729627
TI  - [Investigation of inflammatory responses of alveolar epithelial cells induced by
      lipopolysaccharide and mechanism].
AB  - OBJECTIVE: Lipopolysaccharide (LPS) can activate alveolar epithelial cells (AECs)
      and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally
      involved in LPS signaling and has a requisite role in the activation of NF
      kappaB. NF-kappaB is a key intercellular signaling event that mediates cell
      inflammatory responses. The aim of the study is to investigate in an in vitro
      model the inflammatory responses of AECs induced by LPS and the probable
      mechanism underlined the observed inflammatory responses. So cytokines of ICAM-1,
      TNF-alpha and IL-8 secreted by LPS-activated AECs were observed. And the initial
      signal molecule (the expression of TLR-4 mRNA) and the key intracellular steps
      (the activation of NF-kappaB) were studied in detail. METHODS: The study was
      performed on A549 cells (Human lung adenocarcinoma cell line). A549 cells were
      divided into two groups: control, and LPS interference group. Proinflammatory
      cytokines ICAM-1, TNF-alpha and IL-8 were detected by ELISA or radioimmunological
      methods. The expression of TLR-4 mRNA was detected by real time PCR. The
      activation of NF-kappaB was detected by Western blot (proteins of I-kappaBalpha
      and NF-kappaB p65). RESULTS: Compared with control group, ICAM-1 and TNF-alpha of
      LPS-stimulated group were significantly higher and peaked after 2h before
      gradually declining at 6 and 12 h; IL-8 was higher after 2 h, which continued up
      to 12 h. The expression of TLR-4 mRNA of LPS group was significantly higher and
      peaked after 2 h and gradually declining at 6 and 12 h. Meanwhile, NF-kappaB was
      activated after 0.5, 2, 6 and 12 h indicated by the significant degradation of
      IkappaB-alpha and the significant release of NF-kappaB P65 and its subsequent
      translocation into the nucleus approximately synchronized. CONCLUSION: Taken
      together, the results demonstrate that LPS can induce AECs inflammatory injury
      via activating TLR-4 and subsequently activating NF-kappaB.

PMID- 21729628
TI  - [The effect of intermittent hypoxia with different degrees and frequencies on
      levels of superoxide dismutases and malondialdehyde in vascular endothelial
      cells].
AB  - OBJECTIVE: To investigate the effect of degree and frequency of intermittent
      hypoxia on level of superoxide dismutase (SOD) and malondialdehyde (MDA) in
      vascular endothelial cell. METHODS: We used umbilical vein endothelial cell
      ECV304 to set up cell model. The experiment cell strains contained one control
      group and eight experimental groups. We exposed cells by 3 different degree and 5
      different frequency intermittent hypoxia gas separately as experimental groups,
      and the cells exposed to normal air as a control group. We determined levels of
      SOD and MDA by the way of ELISA in cytoblastema. RESULTS: The level of MDA of
      three different degree intermittent hypoxia groups were higher than the level in
      the control group (P < 0.01). The level of SOD in three different degree hypoxia
      groups is lower than the level in the group (P < 0.01). The level of SOD was
      decreased and the level of MDA was increased gradually with the decreasing of
      hypoxia degree (P < 0.01). There is a trend as the level of MDA and SOD increased
      and decreased with frequency decreased. The level of MDA was no different between
      the group of frequency in 40 per hour and 20 per hour (P > 0.05). When hypoxia
      frequency decreased, the level of MDA increased, and the level of 9.2 per hour
      exposure group was the lowest, but the level of MDA decreased again when the
      frequency was reaching 6.3 per hour (P < 0.01). When hypoxia frequency decreased,
      the level of SOD decreased, and the level of 9.2 per hour group was the highest,
      but the level of SOD decreased again if the hypoxia frequency was reaching 6.3
      per hour (P < 0.01). The level of SOD was negative correlated to that of MDA
      under different hypoxia degree exposure (r = 0.932, P = 0.000), and the level of
      SOD was negative correlated to that of MDA under different frequency exposure (r
      = 0.832, P = 0.000). CONCLUSION: The intermittent hypoxia activates oxidative
      stress reaction in endothelial cells, and that induces the increasing of reactive
      oxygen species, and the antioxygen capacity become weaker. The decreasing and
      increasing of oxidative stress reaction depends on the degree of hypoxia and, is
      correlated to the frequency of hypoxia. Exposed to intermittent hypoxia, the
      balance of oxidative stress reaction and antioxygenative system of endothelial
      cell was disturbed.

PMID- 21729629
TI  - [Endoplasmic reticulum stress and related apoptosis in the lungs of a chronic
      obstructive pulmonary disease rat model].
AB  - OBJECTIVE: To study the endoplasmic reticulum stress (ERS) and the apoptosis of
      alveolar epithelial cells in a COPD rat model. METHODS: Twenty-four Wistar rats
      were divided into a control group and a COPD group at random. The COPD rat model
      was established by intratracheal instillation of lipopolysaccharide (LPS) twice
      and exposure to cigarette smoke daily. The spirometry was conducted and the
      pathological changes were observed after the model was established. The levels of
      glucose regulated protein 78 (GRP78) and CCAAT/enhancer binding protein
      homologous protein (CHOP) mRNA were detected by reverse transcription-polymerase
      chain reaction (RT-PCR). The protein expression of GRP78, CHOP and caspase-12 was
      detected by Western blot. TdT-mediated dUTP nick end labeling (TUNEL) was used to
      analyze alveolar epithelial cell apoptosis. Comparisons between the two groups
      were performed by t-test. RESULTS: Significant decrease of FEV(0.3)/FVC [(60 +/-
      6)%] and dynamic compliance of lung (CLdyn) [(0.17 +/- 0.02) cm H2O*ml(-1)*s(
      1)], and increase of airway resistance [(0.64 +/- 0.07) ml/cm H2O] were found in
      the COPD group compared with the control group [(83 +/- 7)%, (0.31 +/- 0.03) cm
      H2O*ml(-1)*s(-1), (0.32 +/- 0.03) ml/cm H2O] (t = -14.532 - 11.619, P < 0.05).
      GRP78 mRNA and CHOP mRNA densitometry [(0.65 +/- 0.07), (0.79 +/- 0.06)] were
      significantly increased in the COPD group compared with the control group [(0.21
      +/- 0.04), (0.07 +/- 0.04), respectively] (t = -19.102 and -32.573, P < 0.05).
      GRP78, CHOP, and active caspase-12 protein densitometry (0.83 +/- 0.06, 0.82 +/-
      0.06 and 0.81 +/- 0.07) were significantly increased in the COPD group compared
      with the control group [(0.33 +/- 0.05, 0.05 +/- 0.03 and 0.24 +/- 0.06),
      respectively] (t = -40.866 - -22.070, P < 0.05). More apoptotic alveolar
      epithelial cells were found in the COPD group [(32.4 +/- 3.7)%] than in the
      control group [(6.2 +/- 0.9)%] (t = -23.852, P < 0.05). CONCLUSIONS: ERS was
      triggered in the lung tissues of COPD rats, especially in the alveolar epithelial
      cells. Alveolar epithelial cell apoptosis was increased in the COPD group. The
      ERS mediated apoptosis pathway may participate in the alveolar epithelial cell
      apoptosis in COPD.

PMID- 21729630
TI  - [Adult tracheomalacia].

PMID- 21729631
TI  - [Effects and mechanisms of cigarette smoke on asthma].

PMID- 21729632
TI  - Bone-anchored hearing aids (BAHAs) for people who are bilaterally deaf: a
      systematic review and economic evaluation.
AB  - BACKGROUND: A bone-anchored hearing aid (BAHA) consists of a permanent titanium
      fixture, which is surgically implanted into the skull bone behind the ear, and a
      small detachable sound processor that clips onto the fixture. BAHAs are suitable
      for people with conductive or mixed hearing loss who cannot benefit fully from
      conventional hearing aids. OBJECTIVES: To assess the clinical effectiveness and
      cost-effectiveness of BAHAs for people who are bilaterally deaf. DATA SOURCES:
      Nineteen electronic resources, including MEDLINE, EMBASE and The Cochrane Library
      (inception to November 2009). Additional studies were sought from reference lists
      and clinical experts. REVIEW METHODS: Inclusion criteria were applied by two
      reviewers independently. Data extraction and quality assessment were undertaken
      by one reviewer and checked by a second. Prospective studies of adults or
      children with bilateral hearing loss were eligible. Comparisons were BAHAs versus
      conventional hearing aids [air conduction hearing aid (ACHA) or bone conduction
      hearing aid (BCHA)], unaided hearing and ear surgery; and unilateral versus
      bilateral BAHAs. Outcomes included hearing measures, validated measures of
      quality of life (QoL), adverse events and measures of cost-effectiveness. For the
      review of cost-effectiveness, full economic evaluations were eligible. RESULTS:
      Twelve studies were included (seven cohort pre-post studies and five cross
      sectional 'audiological comparison' studies). No prospective studies comparing
      BAHAs with ear surgery were identified. Overall quality was rated as weak for all
      included studies and meta-analysis was not possible due to differences in outcome
      measures and patient populations. There appeared to be some audiological benefits
      of BAHAs compared with BCHAs and improvements in speech understanding in noise
      compared with ACHAs; however, ACHAs may produce better audiological results for
      other outcomes. The limited evidence reduces certainty. Hearing is improved with
      BAHAs compared with unaided hearing. Improvements in QoL with BAHAs were
      identified by a hearing-specific instrument but not generic QoL measures. Studies
      comparing unilateral with bilateral BAHAs suggested benefits of bilateral BAHAs
      in many, but not all, situations. Prospective case series reported between 6.1%
      and 19.4% loss of implants. Most participants experienced no or minor skin
      reactions. A decision analytic model was developed. Costs and benefits of
      unilateral BAHAs were estimated over a 10-year time horizon, applying discount
      rates of 3.5%. The incremental cost per user receiving BAHA, compared with BCHA,
      was L 16,409 for children and L 13,449 for adults. In an exploratory analysis the
      incremental cost per quality-adjusted life-year (QALY) gained was between L
      55,642 and L 119,367 for children and between L 46,628 and L 100,029 for adults
      for BAHAs compared with BCHA, depending on the assumed QoL gain and proportion of
      each modelled cohort using their hearing aid for >= 8 or more hours per day.
      Deterministic sensitivity analysis suggested that the results were highly
      sensitive to the assumed proportion of people using BCHA for >= 8 hours per day,
      with very high incremental cost-effectiveness ratio values (L 500,000-1,200,000
      per QALY gained) associated with a high proportion of people using BCHA. More
      acceptable values (L 15,000-37,000 per QALY gained) were associated with a low
      proportion of people using BCHA for >= 8 hours per day (compared with BAHA).
      LIMITATIONS: The economic evaluation presented in this report is severely limited
      by a lack of robust evidence on the outcome of hearing aid provision. This has
      lead to a more restricted analysis than was originally anticipated (limited to a
      comparison of BAHA and BCHA). In the absence of useable QoL data, the cost
      effectiveness analysis is based on potential utility gains from hearing, that
      been inferred using a QoL instrument rather than measures reported by hearing aid
      users themselves. As a result the analysis is regarded as exploratory and the
      reported results should be interpreted with caution. CONCLUSIONS: Exploratory
      cost-effectiveness analysis suggests that BAHAs are unlikely to be a cost
      effective option where the benefits (in terms of hearing gain and probability of
      using of alternative aids) are similar for BAHAs and their comparators. The
      greater the benefit from aided hearing and the greater the difference in the
      proportion of people using the hearing aid for >= 8 hours per day, the more
      likely BAHAs are to be a cost-effective option. The inclusion of other dimensions
      of QoL may also increase the likelihood of BAHAs being a cost-effective option. A
      national audit of BAHAs is needed to provide clarity on the many areas of
      uncertainty surrounding BAHAs. Further research into the non-audiological
      benefits of BAHAs, including QoL, is required.

PMID- 21729633
TI  - Humerus shaft fractures - where are we today?
AB  - Humeral shaft fractures account for about 1-3% of all fractures. These fractures
      are regarded as the domain of non-surgical management. This is certainly still
      the contemporary view but there is an obvious trend towards surgical
      stabilization. Surgical treatment of humeral shaft fractures has nonetheless been
      greatly facilitated by the development of new implants. In particular, a new
      generation of nails that general permit immediate mobilization have become
      available for improved management of longitudinal and multi-segmental fractures.
      Retrograde and antegrade nails have advantages and disadvantages and selection
      procedure is often based on the distal or proximal location of the fracture.
      Plates also offer an alternative for certain indications and have advantages at
      the proximal and distal shaft in particular. If there is primary lesion of the
      radial nerve, exploration is not very advisable, but in the absence of remission
      exploration can be conducted after several months with the same degree of
      success. Since the published literature offers no comparative studies with a high
      level of evidence, our statement can only be regarded as an up-to-date
      recommendation in the hope that future prospective randomized studies will
      address this issue.

PMID- 21729634
TI  - Cerclage, evolution and potential of a Cinderella technology. An overview with
      reference to periprosthetic fractures.
AB  - Periprosthetic fractures are increasingly frequent. The fracture may be located
      over the shaft of the prosthesis, at its tip or below. The treatment of explosion
      fractures is difficult because the shaft blocks the application of implants, like
      screws, which need to penetrate the medullary cavity. The cerclage, as a simple
      periosteal loop, made of wire or more recently cable, does not only avoid the
      medullary cavity. Its centripetal mode of action is well suited for reducing and
      maintaining radially displaced fractures. Furthermore, the cerclage lends itself
      well for minimally invasive internal fixation. New insight challenges the
      disrepute of which the cerclage technology suffered for decades. The outcome of
      cerclage fixation benefits from an improved understanding of its technology,
      mechano-biology and periosteal blood supply. Preconceived and generally accepted
      opinions like "strangulation of blood supply" need to be re-examined. Recent
      mechanical evaluations demonstrate that the wire application may be improved but
      cable is superior in hand- ling, maintenance of tension and strength. Beside the
      classical concepts of absolute and relative stability a defined stability
      condition needs consideration. It is typical for cerclage. Called "loose-lock
      stability" it specifies the situation where a loosened implant allows first
      unimpeded displacement changing abruptly into a locked fixation preventing
      further dislocation.

PMID- 21729635
TI  - [Vascular injuries in joint replacement surgery].
AB  - Iatrogenic injuries to blood vessels in joint replacement surgery are rare events
      that occur as few per thousand. However, their sequelae are serious. The patient
      may either bleed to death, because vascular injury is not obvious and therefore
      difficult to diagnose, or lose the limb due to ischaemia. The highest risk of
      vascular injury is associated with repeat surgery and loosening of the acetabular
      component. We distinguish sharp and blunt force injuries. The former are caused
      by implants, sharp instruments, bone fragments or bone cement debris. The latter
      arise from stretching over a part of implanted material. Bleeding can be
      inapparent or apparent. Inapparent bleeding is difficult to diagnose and is
      recognized from the dynamics of blood losses. Haemodynamic instability or, in a
      worse case, even hypovolaemic shock may be the only signs of bleeding. Occlusion
      of an artery is manifested by limb ischaemia. The seriousness and progression of
      ischaemia depends on the rate of arterial occlusion, potential pathways for
      collateral circulation and the degree of atherosclerotic vascular disease. The
      patient with conduction anaesthesia does not feel pain and therefore the
      diagnosis must primarily be based on arterial pulsation in the limb and its skin
      colour. A pseudoaneurysm can develop due to a partially weakened vascular wall
      and its rupture is a life-threatening complication. Its presence is recognized as
      a pulsating mass in the groin. An arterio- venous fistula which arises from
      traumatic communication between the two vessels may lead to cardiac failure. The
      diagnosis is based on examination by sonography and digital subtraction
      angiography. The results of CT angiography and MR angiography are difficult to
      evaluate because of the presence of metal implants. In apparent bleeding it is
      sometimes difficult to locate the source. It is recommended to perform digital
      compression and gain access to the vessels from the extraperitoneal approach.
      When an expanding haematoma or ischaemia is present, the artery can be treated by
      surgical exploration or percutaneous transluminal angioplasty. A possibility of
      vascular injury should be taken into account particularly in revision
      arthroplasty. To check blood flow in the limb before surgery is advisable. If the
      procedure entails a significant risk of post-operative complications, a vascular
      surgeon should be available. In the case of acute intra-operative bleeding, the
      source should be localised as soon as possible, the site compressed and an expert
      assistance called in. When the source is not obvious, it should not be attempted
      to apply vascular clamps or clips at random; this may do even more damage to the
      vessel.

PMID- 21729636
TI  - Cerclage handling for improved fracture treatment. A biomechanical study on the
      twisting procedure.
AB  - PURPOSE OF THE STUDY: Twisting is clinically the most frequently applied method
      for tightening and maintaining cerclage fixation. The twisting procedure is
      controversially discussed. Several factors during twisting affect the mechanical
      behaviour of the cerclage. This in vitro study investigated the influence of
      different parameters of the twisting procedure on the fixation strength of the
      cerclage in an experimental setup with centripetal force application. MATERIAL
      AND METHODS: Cortical half shells of the femoral shaft were mounted on a testing
      fixture. 1.0 mm, 1.25 mm and 1.5 mm stainless ste- el wire cerclages as well as a
      1.0mm cable cerclage were applied to the bone. Pretension of the cerclage during
      the installation was measured during the locking procedure. Subsequently, cyclic
      testing was performed up to failure. RESULTS: Higher pretension could be achieved
      with increasing wire diameter. However, with larger wire diameter the drop of pre
      tension due to the bending and cutting the twist also increased. The cable
      cerclage showed the highest pretension after locking. Cerclages twisted under
      traction revealed significantly higher initial cerclage tension. Plastically
      deformed twists offered higher cerclage pretension compared to twists which were
      deformed in the elastic region of the material. Cutting the wire within the twist
      caused the highest loss of cerclage tension (44% initial tension) whereas only 11
      % was lost when cutting the wire ends separately. The bending direction of the
      twist significantly influenced the cerclage pretension. 45% pretension was lost
      in forward bending of the twist, 53% in perpendicular bending and 90% in backward
      bending. CONCLUSION: Several parameters affect the quality of a cerclage
      fixation. Adequate installation of cerclage wires could markedly improve the
      clinical outcome of cerclage.

PMID- 21729637
TI  - [Kyphotic deformities of the cervical spin].
AB  - PURPOSE OF THE STUDY: The development of a cervical kyphotic deformity can be
      associated with a degenerative disease, trauma, tumour, developmental anomaly and
      also a surgical procedure. Post-operative kyphosis can develop after both the
      anterior and posterior surgical approaches. The deformity can also result from
      systemic diseases, such as ankylosing spondylitis or rheumatoid arthritis. The
      aim of the study was to make the clinical and radiographic evaluation of a group
      of patients with kyphotic deformity treated at our department. MATERIAL: Between
      May 2005 and April 2010, a total of 102 patients underwent correction of cervical
      kyphosis at our department. (Center for Spinal Surgery). Of them, 90 patients
      with complete medical records and post-operative periods longer than 6 months
      were included in this study. There were 36 men and 54 women ranging in age from
      13 to 90 years and with an average of 56.7 years. In six patients cervical
      kyphosis was caused by an inveterate injury, in 71 by degenerative disease, in
      six it developed in association with rheumatoid arthritis, and in seven patients
      it was due to previous surgery. Patients with acute trauma, tumour, infectious
      disease or congenital anomaly were not included. METHODS: All patients were
      examined before surgery by radiography in antero-posterior and lateral
      projection, including flexion- extension bending films, and by CT scanning of
      ultrathin cross-sections with sagittal, frontal and recently also 3D
      reconstructions. Magnetic resonance imaging in three planes was also performed.
      On the basis of the results and clinical examination, the operative strategy was
      planned. Surgery was carried out from the anterior or the posterior approach, or
      the combined approach was used. Three-stage surgery was performed in one patient.
      The surgical outcome was assessed using the Nurick score and Neck Disability
      Index (NDI), the Visual Analogue Scale (VAS) was used to evaluate pain intensity
      or paraesthesia. Statistical analysis was done using the Chi-square test and
      paired t-test. RESULTS: The average NDI value was 25.5 before surgery and 14.3
      and 14.9 at one and two years after surgery, respectively. Compared with the pre
      operative state, improvement or no changes were recorded in 89.7 % of the
      patients; transient deterioration occurred in 10.3 %. Improvements found were as
      follows: by one degree in 46.2 % of the patients, by two degrees in 18 %, by
      three degrees in 5.1 % and by five degrees in 2.6 % of the patients. The
      condition remained unchanged in 18 % of the patients. The average outcome was an
      improvement by one degree. The average pre-operative Nurick score was 0.7; an
      average post-operative value of 0.6 was recorded at both one and two years of
      follow-up. The average VAS value for neck and radicular pain was 5.7 pre
      operatively, and 2.5 and 2.7 at one and two post-operative years, respectively.
      Out of 90 patients, complete bone union was achieved at 6 months after surgery in
      88 patients (97.8 %). The average pre-operative value for the cervical curvature
      index (Ishihara) was -13.7; the average pre-operative cervical kyphosis was -14.4
      degrees, ranging from -2.2 to -44.0 degrees. After surgery, the average Ishihara
      index was +15.3 and the average lordosis was +13.5 degrees, with a range of -16.0
      to + 37.4 degrees. DISCUSSION: A single/isolated anterior approach can be used
      for fixed deformities without ankylosing spondylitis. It allows for decompression
      of the anterior pathology and for correction of cervical kyphosis with use of
      instrumentation and structural graft. A combined ventral-dorsal approach is
      appropriate in fixed deformities or deformities involving the cervico-thoracic
      junction. The main principle of correction is to lengthen the cervical spinal
      column in the front and to shorten it at the back by anterior decompression with
      or without instrumentation and by subsequent posterior stabilisation. An
      isolated/single dorsal correction can be used in the case of successful
      correction by traction or specific head positioning on the table without anterior
      nerve compression. In severe fixed deformities such as Bekhterev's disease, the
      chin can be so close to the chest as to interfere with eating and breathing. The
      deformity most often develops at the cervico-thoracic junction and requires
      treatment by osteotomy. CONCLUSIONS: The results of the study showed a marked
      improvement in the patients' quality of life after kyphosis correction, improved
      neurological status and an improved posture seen on radiograms of the cervical
      spine. The study also revealed a higher number of potential complications
      associated, in particular, with corrective osteotomy. The best results were
      achieved with the combined surgical approach; however, the choice of a surgical
      method was independent of the patient's clinical status.

PMID- 21729638
TI  - [Valgus high tibial osteotomy - long-term results].
AB  - PURPOSE OF THE STUDY: The aim of the study was to evaluate the long-term results
      in a group of patients treated by proximal tibial valgus osteotomy. MATERIAL: A
      group of 92 high tibial osteotomies performed in the 1985/1994 period were
      evaluated. All were indicated for primary osteoarthritis. Closing wedge osteotomy
      was the technique used. Staple-fixed osteotomy was immobilised in a plaster cast
      for 6 weeks in 44 cases. Osteotomy fixed with a plate in 35 or with a cerclage in
      13 cases was immobilised for two weeks. METHODS: Recurrent intensive pain and
      walking problems were regarded as a termination of the favourable effect of
      osteotomy. This was evaluated by the Kaplan-Meier survival analysis. The tibio
      femoral angle 5 to 10 degrees of valgus was considered as an optimal deformity
      correction. The results were compared in relation to complications, correction,
      duration of immobilisation and patient age. RESULTS: The mean age of the patients
      was 59.8 +/- 8.7 years (range, 42 to 78). During surgery, medial unicompartmental
      arthritis, grade II or higher, was recorded in 59 patients (64.1%) and
      multicompartmental knee arthritis was found in 66 patients (71.7%). The absence
      of noticeable problems was reported by 80.4% of the patients at 10 years and by
      30.4 % at 15 years after osteotomy. Surgery decreased the range of motion from
      100 +/- 6.9 to 94.5 +/- 17.7 degrees flexion (p = 0.04). Poor correction and post
      operative complications were found in 21 patients (22.8 %) who also experienced
      significantly worse outcomes (p = 0.003). Good results after 10 and 15 years were
      reported by 47.6% and 14.3% of the patients, respectively. Of 71 patients (77.2%)
      who had good correction and surgery without complications, the osteotomy showed a
      good effect in 90.1% at 10 post-operative years and in 35.2% at 15 years. A
      longer immobilisation resulted in significantly worse results (p = 0.04) and a
      restricted range of motion (p = 0.02). The patients younger than 60 years
      achieved better results than the elderly patients (p = 0.38), but the difference
      was not significant. DISCUSSION: Good results were recorded up to 10 years after
      osteotomy, although some patients had had worse arthritis than recommended for
      this procedure. Inadequate correction and complications deteriorated the effect
      of osteotomy. With the opening wedge technique it is easier to achieve good
      correction, and stable fixation allows for active physical therapy. Better long
      lasting results are achieved with total knee arthroplasty (TKA). However, in
      young active adults TKA can fail prematurely. Osteotomy can postpone the
      necessity of this implantation. If TKA is performed after osteotomy, functional
      outcomes are similar to those after primary implantation. CONCLUSIONS: Corrective
      osteotomy is an effective method in patients below 60 years who have an early
      stage osteoarthritis of the knee with axial mal-alignment. If the tibio-femoral
      angle is over-corrected to more than 10 degrees valgus, patelo-femoral pain will
      ensue. Post-operative active physical therapy is necessary. After bone healing,
      implants must be removed. Corrective osteotomy has not been overcome by the
      development of joint replacement techniques, but both methods are complementary
      in the treatment of osteoarthritis.

PMID- 21729639
TI  - [Baker's procedure in the treatment of pes equinus in cerebral palsy patients].
AB  - PURPOSE OF THE STUDY: Surgical procedures on muscles in cerebral palsy are
      regarded as essential interventions. The tactics for surgery on the triceps surae
      muscle in the treatment of spastic pes equinus involve several surgical options
      at different muscle levels. MATERIAL AND METHODS: In the 1992-2008 period,
      Baker's procedure, prolongation of the triceps muscle in the common part of the
      gastrocnemius and soleus aponeuroses, was indicated in 114 children, aged between
      3 and 18 years, mostly with spastic hemipleia (45.7 %) or diplegia (42.9 %). In
      both groups, the isolated Baker's procedures and the combined procedures were
      clinically assessment at 2 and 6 months after surgery. RESULTS: Clinical
      examination at a follow-up of 8 weeks showed that all patients achieved 5 to 10
      degrees of dorsiflexion of the foot. A maximum of Achilles tendon stretch-out was
      achieved in seven patients (6.14%) after 6 months. In one patient (0.9%) an
      excessive dorsiflexion was recorded. DISCUSSION: The choice of surgical tactics
      for treatment of spastic pes equinus is related to a positive or a negative
      result of the Silfverskiold test, because this shows the degree of contracture of
      the gastrocnemius and soleus muscles. Prolongation at their joint aponeurosis
      should be indicated when the test shows partly positive results, and muscle
      balance at all levels of the lower extremity should be maintained. CONCLUSIONS:
      Baker's procedure is one of the options to treat spastic pes equinus. The surgery
      is indicated primarily in isolated pes equinus and in children with spastic
      hemiplegia with low risk of Achilles tendon excessive elongation. Key words: pes
      equinus, Silfverskiold test, Baker's procedure.

PMID- 21729640
TI  - [Arthroscopic findings concerning rotator cuff lesions and their operative
      management].
AB  - PURPOSE OF THE STUDY: Our objective is to introduce our simplified, easy-to-use
      classification of rotator cuff (RC) lesions, describe the frequency of individual
      findings in a considerably large series of shoulder joints examined by
      arthroscopy, evaluate the results of the operative management of individual
      lesion types, and recommend optimal surgical approaches. MATERIAL: Over the
      course of 10 years (between October 1st, 2000 and December 31st, 2009), 756
      arthroscopic operations on the shoulder joint were performed. RC lesions were
      identified in 516 cases. We categorized the lesions using our own classification.
      Patient characteristics were as follows: the mean age was 43 years, 69% of the
      patients were men, and the right shoulder was affected in 61% of the cases (with
      the dominant upper limb being affected in 71% of the cases). The patients were
      followed up for a minimum period of 6 months. METHODS: All operations were
      performed in the "beach-chair" position under general anesthesia or in an
      interscalenic block. The arthroscope was introduced into the shoulder joint
      through the "soft-spot". Continuous lavage via an arthroscopic pump was used. The
      glenohumeral joint was examined first; an examination of the subacromial space
      followed. Once the lesion type was identified, other procedures were performed.
      In standard situations, type I lesions were managed with ASK sub- acromial
      decompression (SAD). As to type II lesions, we initially performed open RC
      reconstruction with acromioplasty, which we later replaced with ASK-assisted RC
      reconstruction with SAD; we are currently managing these lesions with ASK RC
      reconstruction + SAD. As for type III lesions, we initially used to treat them
      with open RC reconstruction with acromio - plasty; we are now performing ASK
      assisted RC reconstruction with mini-incision + SAD. We are trying to use "double
      row" sutures in certain cases. The initial management of type IV lesions
      consisted of ASK palliative resection of RC remnants combined with SAD.
      Currently, we are performing partial muscle transfer of the intact subscapularis
      muscle tendon (Karas) or partial non-anatomical RC reconstruction (Burkhart). A
      combination of both methods described above was required in some cases. If
      delamination of the RC was found, partial reconstruction using the "double-layer"
      technique took place. Open acromioplasty was added during all operations. Type V
      lesions are managed with ASK palliative resection of RC remnants + SAD; when this
      approach proves unsuccessful, which is a rare phenomenon, resurfacing follows.
      The results were evaluated after 6 months using a modified Constant functional
      score. Besides clinical examination, self-assessment questionnaires filled in by
      the patients were also evaluated. RESULTS: Out of a total of 516 RC lesions, type
      I was the most prevalent (54%), followed by type V (16%). The prevalence of
      lesion types II, III and IV was about 10% each. In type I, the mean improvement
      measured by the Constant score was 36 points. As for type II, open
      reconstruction, ASK-assisted reconstruction and ASK reconstruction resulted in
      mean improvements of 31, 34, and 35 points, respectively. While open
      reconstruction of type III lesions was associated with a 27-point improvement on
      the Constant score, the use of ASK-assisted reconstruction resulted in a 29-point
      improvement. In type IV, the use of ASK palliative resection of RC remnants,
      muscle transfer (Karas), partial reconstruction (Burkhart), and a combination of
      the last two methods led to the mean 19-, 25-, 22-, and 22- point improvements
      respectively. Following ASK palliative resection, the mean Constant score
      improvement in type V lesions was 17 points, while the use of resurfacing, if
      performed, was associated with a 21-point improvement. DISCUSSION In type I
      lesions, favourable long-term outcomes are achieved through ASK SAD, which
      removes RC irritation within the narrowed subacromial space. RC reconstruction or
      sutures, which can be performed arthroscopically quite easily, are indicated in
      type II lesions. The situation is similar in type III lesions, where, from a
      technical point of view, reconstruction is facilitated by ASK-assisted
      reconstruction with mini-incision. Since type IV lesions are the most complex
      ones, the largest number of surgical management methods is described here. As for
      muscle transfer, the subscapularis and latissimus dorsi muscles are used most
      often, the latter requiring wider surgical access. Partial non-anatomical
      reconstruction is useful, too. New synthetic prostheses, as well as biosynthetic
      or biologic prostheses prepared with cultures of pluripotent stem cells, have
      been developed recently. Unlike some other authors, we prefer open surgery.
      Attempts at ASK reconstruction increase surgical time considerably, while the
      cosmetic effect is negligible if many ASK ports are used. Reconstruction is
      contraindicated in type V lesions; good outcomes are being achieved with ASK
      palliative resection of RC remnants (Apoil). Type I lesions are successfully
      managed with ASK SAD. The method of choice in type II lesions is ASK
      reconstruction. In type III lesions, we have been getting good results with ASK
      assisted RC reconstruction with mini-incision. As for type IV lesions in older
      patients, we have good experience with muscle transfer of a part of the intact
      subscapularis muscle tendon (Karas); partial non-anatomial reconstruction
      (Burkhart) is deemed more beneficial in younger and more active patients. For
      anatomical reasons, a combination of both above-mentioned methods had to be used
      in some cases. ASK palliative resection of RC remnants, rarely followed by
      resurfacing when unsuccessful, remains the method of choice in treating type V
      lesions. Key words: shoulder arthroscopy, rotator cuff lesions, classification,
      subacromial decompression, reconstruction, open surgery, palliative resection,
      Constant Functional Score.

PMID- 21729641
TI  - [Femoral lengthening. A critical review of ten-year results].
AB  - PURPOSE OF THE STUDY: To evaluate the results of femoral lengthening in the
      patients treated from 2000 to 2009 in whom complete radiographic data were
      available and the lengthening procedure involved mainly the use of a Mephisto
      fixator. MATERIAL AND METHODS: A total of 28 femoral lengthening procedures were
      carried out in 26 patients,16 girls and 10 boys. The external fixator Mephisto
      was used in 24 cases; fixators Prospon and Orthofix in one and three cases,
      respectively. Fifteen patients were treated for congenital short femur, the rest
      had secondary femoral shortening due to following pathologies: distal femoral
      epiphysiolysis in five children, proximal femoral osteomyelitis in one child,
      avascular necrosis of the femoral head in one, diaphyseal femur fracture in one,
      enchondromatosis of the distal femur with growth plate destruction in one, and
      contralateral femur overgrowth following a fracture in one child. The average age
      at the beginning of treatment was 11 (range, 4-16) years. Complications were
      classified as mild, serious and critical. The results were statistically analysed
      using several statistical tests. RESULTS: The average parameter values for the
      group included: total femoral lengthening, 40.2.mm (SD+/-11.1); osteotomy index
      (OI), 41 % (SD+/-9.8); lengthening percentage (LP), 10.9 % (SD+/-3.8);
      lengthening index (LI), 14.5 (SD+/-3.5) days/cm; hea- ling index (HI), 52.6 (SD+/
      20.1) days/cm; and consolidation index (CI), 93.3 (SD+/-40.0) days/cm. Mild
      complications were recorded in 11 (39.2 %), and serious and critical in eight
      patients (28.6 %). Fourteen patients (53.8 %) were free of any complications. Two
      complications were concurrently found in five patients (17.9 %). There was a
      statistically significant difference in the LP values related to the number of
      complications (p=0.019). No significant relationship was recorded on comparison
      of the HI value with the patient's age at the time of surgery (p=0.836) and
      patient's gender (p=0.546) (Mann- Whitney test). The relationship of the OI value
      to the HI value was non-significant (p=0.492), as was the relationship between
      the osteotomy technique (oscillating or Gigli saw osteotomy) and the occurrence
      of complications (p=1.000) (Fisher's exact test). Correlation between the LI and
      HI values was significant (p<0.001). DISCUSSION: The results of healing after
      lengthening, as assessed by the healing and the consolidation index, were in
      agreement with other authors' data. The lower number of complications,
      particularly fractures of bone regenerate, can be explained by the facts that, in
      our study, the lengthening percentage was lower and that the post-operative care
      was strictly observed, including dynamic axial loading which stimulates bone
      consolidation at the lengthened section, with adherence to the proof of three
      developed cortices. CONCLUSIONS: Our results did not confirm the assumption that
      slower lengthening will have a favourable effect on the healing index. Key words:
      femoral lengthening, external fixator, complications.

PMID- 21729642
TI  - [Developmental dysplasia of the hip - epidemiological determinants and age
      assessment regarding time of surgical correction].
AB  - PURPOSE OF THE STUDY: Aim of the study was to analyze age structure of the
      patients with developmental dysplasia of the hip (DDH) at the time of the
      operation and epidemiological determinants: gender distribution, proportion of
      left or right hip affection, type of delivery and mode of labor presentation.
      MATERIAL AND METHODS: The population of 78 children with DDH was evaluated. Three
      age groups were analyzed: first group younger than 24 months of life, second
      group between 24 and 48 months and third group older than 48 months of life. Male
      and female gender was separately evaluated as well as type of delivery and mode
      of labor presentation. Separately, 2 groups regarding affected hip were analyzed:
      group with affected left hip and group with affected right hip. Radiographic
      findings (Collodiaphyseal angle, Hilgenreiner angle and Wibergs center-edge
      angle) and clinical findings (positive Trendelenburgs sign, reduced flexion angle
      (<114 degrees ), pain in the hip and incomplete crouch) were evaluated regarding:
      age of the patients, gender, mode of presentation and type of delivery. RESULTS:
      There was 33.3% of patients in the first age group, 46.2% of patients in second
      group and 20.5% of patients in third age group, and regarding gender, 17.9% of
      males and 82.1% of females. Vaginal delivery was predominant mode with
      distribution of 87.2% as well as head presentation with distribution of 71.8%.
      Distribution of children with affected left hip was 46.2% and right hip 53.9%.
      DISCUSSION: Majority of patients in the study were in the age group between 24
      and 48 months of life, suggesting delay in on-time diagnostics of DDH. Female
      gender was more frequently affected by DDH and vaginal delivery as well as head
      presentation of newborn was significantly frequent in patients with DDH. It is
      shown that Collodiaphyseal, Hilgenreiner and Wibergs center-edge angles values
      are in correlation with the age structure of the patients with DDH at the time of
      diagnosis. Male gender tends more frequently to present with clinical findings.
      Reduced flexion angle of the hip is the frequent clinical finding for children
      with DDH that were born by breech presentation or delivered by Caesarean section.
      CONCLUSION: Female gender can be taken as one of possible risk factors during
      clinical examination of newborn regarding diagnostics of DDH, while breech
      presentation has been shown not to be one of possible risk factors. Early
      diagnostics and prompt treatment are beneficial in overall outcome for children
      with DDH. Therefore, there is great need for countinous education of orthopedic
      surgeons and pediatricians.

PMID- 21729643
TI  - [A contribution of instrumental gait analysis to the establishment of surgical
      indications in cerebral palsy].
AB  - PURPOSE OF THE STUDY: To evaluate our experience with indications for surgery
      based on instrumental gait analysis in cerebral palsy children, and to compare
      them with those drawn from the results of clinical examination. MATERIAL AND
      METHODS: The gait analysis laboratory was built in the Paediatric Hospital of the
      Faculty of Medicine in Brno in the 2008/09 period with support of the Norwegian
      funds. It is equipped with eight optical cameras, two auxiliary motion-picture
      video came- ras, two force platforms and a telemetry system for electromyography.
      Between June 2009 and March 2010 a total of 297 children with spastic cerebral
      palsy, 66 with hemiparesis and 231 with diparesis were examined. RESULTS: On the
      basis of instrumental gait analysis, indications for surgery were established in
      19 hemiparetic and 88 diparetic patients, which meant a new indication in 107
      children. In 14 children, the results of gait analysis led to abandoning former
      indications for surgery based on clinical examination only while, in 13 children,
      they backed up the surgical indications in spite of the negative results of
      clinical examination. In six children a so-called superclinical decision was
      made, i.e., the results of repeated clinical examinations over-weighed those of
      instrumental gait analysis either in favour of or against surgery. DISCUSSION:
      Based on the gait analysis results, a change in treatment plans was made in 27
      out of 297 children (9 %). This is in contrast with the findings of other authors
      who report a much higher rate of treatment planning changes (52-70 %) In our stu-
      dy the use of instrumental gait analysis allowed us to decrease the frequency of
      surgical indications by 4.7 %. Other authors have achieved a higher value, up to
      13 %. Unlike other studies, ours did not confirm the effect of gait analysis
      outcomes on an increase in the number of one-stage multi-level surgical
      procedures. CONCLUSIONS: Instrumental gait analysis is a great contribution to
      the diagnosis of movement disorders in children with cerebral palsy.

PMID- 21729644
TI  - [A contribution of multidetector computed tomography to indications for chest
      wall stabilisation in multiple rib fractures].
AB  - PURPOSE OF THE STUDY: Multidetector computed tomography (MDCT) is more sensitive
      for the detection of injury to the thoracic wall and intra-thoracic organs than a
      plain chest radiograph. The chest wall deformity and instability following
      multiple rib fracture involves fractures of four or more adjacent ribs at two
      levels, sometimes including a sternal fracture. It may also be associated with
      lung trauma (pneumothorax, haemothorax, rupture, laceration or pulmonary
      contussion). An isolated multiple-rib fracture can successfully be treated
      conservatively. Early intubation and mechanical ventilation are indicated in
      patients with progressive respiratory insufficiency. Indications for surgical
      stabilisation of this fracture are based on the signs of respiratory failure and
      the results of imagining methods (MDCT at the present time). MATERIAL AND
      METHODS: Examination by MDCT was carried out in patients with severe thoracic
      trauma. In five patients with multiple rib fractures, the CT findings were
      included in indication criteria for open rib osteosynthesis and thoracotomy. A
      clinical indication criterion was respiratory insufficiency after the patient's
      weaning from a ventilator, manifested by paradoxical chest motion. A radiographic
      indication included an extensive chest deformity with rib displacement into the
      pleural cavity in 3D reconstruction from MDCT images. Surgery was performed
      within one hour to five days of admission. Access was gained through an oblique
      skin incision and by cutting though the chest wall muscles to release fractured
      ribs. To explore the thoracic cavity, a defect in the intercostal muscles was
      extended by an incision at the site of rib fracture. Suction of a haemothorax was
      done and lung ruptures were sutured in three patients. After chest drain
      insertion, the fractured ribs were stabilized by plate osteosynthesis (fy Medin).
      RESULTS: In the post-operative period, mechanical ventilation was continued for 3
      to 6 days in four patients. There were no complications. In the patients with
      flail chest, the 3D reconstruction from MDCT images allowed us to make more exact
      pre- operative decisions concerning the extent of rib osteosynthesis and the
      method of exposure. If lung injury was also shown, this was an indication for
      thoracic cavity exploration. DISCUSSION: The pathophysiological effects of flail
      chest involve several factors including the size of a flail segment, change in
      intra-thoracic pressure during spontaneous breathing and multiple injuries to the
      intra-thoracic organs. Therapy is related to the seriousness of respiratory
      disorder associated with flail chest, the degree of chest wall deformity and
      other complications of conservative treatment (dependence on mechanical
      ventilation with no possibility of weaning). Surgical stabilization of the chest
      wall is the most reliable method of treatment which allows us to avoid or
      interrupt the adverse effect of rib displacement and chest instability. A
      contribution of MDCT examination to the indication for surgical stabilization
      lies in that MDCT provides imagining of the details decisive for the
      classification of fracture types including their tendency to displacement. MDCT
      permits a better visualisation of chest injury and a better understanding of the
      respiratory disorder. CONCLUSIONS: Based on 3D reconstruction from MDCT images,
      it is possible to make the pre-operative considerations for rib osteo- synthesis
      more specific and to choose the best approach. At the same time MDCT enables us
      to diagnose associated intra-thoracic injuries and provides indications for their
      treatment. In addition, it gives us a possibility to evaluate the role of a flail
      segment in breathing dysfunction and to establish indications for surgical
      stabilization in multiple rib fractures. Rib osteosynthesis allowed for early
      stabilization of the chest wall and improved the mechanics of breathing, thus
      requiring a shorter period of mechanical ventilation. The evaluation of
      statistical significance of these facts will be made when a larger group of
      patients examined by MDCT is available.

PMID- 21729645
TI  - [Failed compression osteosynthesis of the dens axis treated by anterior C1-C2
      transarticular stabilisation. Case report].
AB  - We describe the case of an 80-year-old female patient who had undergone anterior
      C1-C2 transarticular stabilisation and was subsequently treated by the triple
      screw method for failed compression osteosynthesis of a AO type III dens axis
      fracture. Key words: dens axis, upper cervical spine fracture, eldery, triple
      screw technique, anterior transarticular C1-C2 stabilisation.

PMID- 21729646
TI  - Immunohistochemical overexpression of platelet-derived growth factor receptor
      beta (PDGFR-beta) is associated with PDGFRB gene copy number gain in sarcomatoid
      non-small-cell lung cancer.
AB  - Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant
      that has not been molecularly well-characterized. We conducted
      immunohistochemical and fluorescence in situ hybridization studies of PDGF
      B/PDGFR-b on archived surgically resected specimens and showed high PDGFR-b IHC
      expression and gene copy number gain. Further studies are warranted to determine
      whether PDGFR-b is a feasible therapeutic target in this population.
      INTRODUCTION: Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon
      histologic variant that has not been molecularly well-characterized. We
      hypothesized that the PDGF-B/PDGF-Rbeta pathway may be dysregulated in
      sarcomatoid lung cancer. METHODS: We conducted immunohistochemical (IHC) and gene
      copy number gain studies of PDGF-B/PDGFR-beta on archived surgically resected
      specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and
      stage-matched. Biomarkers were correlated to patient demographics, tumor
      characteristics, and survival. RESULTS: Sarcomatoid tumors had higher PDGFR-beta
      IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No
      difference was seen between the two groups of PDGF-B IHC expression; and neither
      PDGF-B nor PDGFR-beta IHC levels correlated with gender, age, clinical or
      pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated
      by FISH using three ways: presence of amplification, gene copy number gain, and
      gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was
      associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic
      T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013).
      Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher
      gene copy ratios above 1.83. Higher PDGFR-beta IHC expression in tumor cells was
      associated with gene copy number gain (P = 0.021) and higher gene copy ratio
      status (P = 0.005). CONCLUSION: This is the first study to demonstrate high PDGFR
      beta IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and
      suggests that further studies are warranted to determine whether PDGFR-beta is a
      feasible therapeutic target in this population.

PMID- 21729647
TI  - Clinical outcomes of extensive stage small cell lung carcinoma patients treated
      with consolidative thoracic radiotherapy.
AB  - The purpose of this review was to determine the effect of consolidative thoracic
      radiotherapy (TRT) in patients with extensive stage small cell lung cancer (ES
      SCLC) with minimal metastatic disease. Locoregional failure, distant failure and
      OS were 39%, 74% and 14% respectively at 2 years. No patients experienced
      clinical pneumonitis. Consolidative TRT is well tolerated in selected patients
      with ES-SCLC. OBJECTIVES: To determine the rates of loco-regional (LR) failure
      and toxicity in extensive-stage small cell lung carcinoma (ES-SCLC) patients
      treated with consolidative thoracic radiotherapy (TRT). METHODS: A retrospective
      review was conducted on SCLC patients treated from January 2005 to July 2009.
      Patients with ES-SCLC who received consolidative TRT >=30Gy were identified.
      Sites of disease failure, toxicity Common Terminology Criteria for Adverse Events
      version 3.0, incidence, and cause of treatment delays and vital status were
      determined. The cumulative LR and distant failure rates were calculated.
      Progression-free and overall survivals (OS) were determined by the Kaplan-Meier
      method. RESULTS: Three hundred thirty-six patients were identified with a
      diagnosis of SCLC and 215 patients had ES-SCLC. Nineteen (9%) patients were
      identified as receiving >=30Gy consolidative TRT. Of this subgroup, the median
      age was 60 years (range 47 years to 82 years) and the median follow-up was 13
      months (range 8 months to 32 months). Consolidative TRT was 40Gy/15 fractions (n
      = 16), 45Gy/30 fractions delivered twice daily (n = 2) and 36Gy/12 fractions (n =
      1). Chemotherapy was sequential (n = 11) or concurrent (n = 8) with consolidative
      TRT. The incidence of LR failure was 26% and 39% at 1 and 2 years, respectively.
      The incidence of distant failure was 58% and 74% at 1 and 2 years, respectively.
      The median OS was 14 months. The 1-year and 2-year OS was 58% and 14%,
      respectively. No patients experienced clinical pneumonitis requiring treatment.
      CONCLUSIONS: Consolidative TRT controlled LR disease in most patients with
      minimal acute toxicity, though distant failure remained a significant problem.

PMID- 21729648
TI  - Biomarkers, prediction, and prognosis in non-small-cell lung cancer: a platform
      for personalized treatment.
AB  - In lung cancer, the introduction of targeted agents in those patients who carry a
      genetic abnormality has resulted in better clinical outcomes with better quality
      of life. These molecular abnormalities have also become predictive biomarkers. It
      is imperative that we continue searching for these biomarkers in different
      tumorigenesis pathways, so we can provide the most appropriate therapy to each
      individual in the near future. Since the 1980s, chemotherapy for patients with
      advanced non-small-cell lung cancer has been shown to provide a small improvement
      in survival. In the early 1990s, platinum-based regimens became the backbone of
      treatment for this disease. In 2002, the Eastern Cooperative Oncology Group 1594
      clinical trial showed that there was no overall survival difference among four
      common chemotherapy regimens used in non-small-cell lung cancer. It was not until
      2006 when the introduction of biologic agents into the field of lung cancer
      improved, for the first time ever, median overall survival beyond 1 year. To
      date, we recognize that there are differences between all histologic subtypes of
      non-small-cell lung cancer in terms of their response to specific agents. All
      these plus the introduction of molecular medicine have resulted in the
      identification of markers for prognosis and prediction in lung cancer. In this
      review, we describe the actual and ongoing clinical efforts to validate the
      prognostic and predictive value of these potential markers in lung cancer. We
      hope that the clinical use of biomarkers will help us to deliver personalized
      medicine to our lung cancer patients by improving their quality of response which
      may translate into further survival advantage.

PMID- 21729649
TI  - Induction chemotherapy with triweekly docetaxel and cisplatin followed by
      concomitant chemoradiotherapy with or without surgery in stage III non-small-cell
      lung cancer: a phase II study.
AB  - BACKGROUND: The main goal of this study was to evaluate the feasibility and
      effectivity of triweekly docetaxel/cisplatin followed by weekly
      docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in
      locally advanced non-small-cell lung cancer (NSCLC) patients. MATERIALS AND
      METHODS: Thirty five patients with locally advanced NSCLC were enrolled.
      Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m(2)) was
      administered as induction regimen. After induction chemotherapy, patients were
      evaluated for surgery if their disease subsequently downstaged. Six cycles of
      weekly docetaxel/cisplatin (20 mg/m(2)) concurrently with radiotherapy up to a 60
      Gy were administered after induction chemotherapy with or without surgery.
      Response, toxicity, time-to-progression and overall survival were evaluated.
      RESULTS: Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0
      2 were evaluated (median age, 54 years). After 94 cycles of induction
      chemotherapy, partial response was achieved in 20 patients, 9 patients had stable
      disease and six had progressive disease. After overall treatment, 6 patients
      achieved complete response, 19 patients had partial response, 8 patients had
      progressive disease, and 2 patients had stable disease. Two patients experienced
      grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal
      toxicity. Six patients underwent surgery. Median overall survival for all
      patients was 15 months and time-to-progression was 13 months with a median follow
      up of 22 months. CONCLUSION: Triweekly docetaxel plus cisplatin followed by
      weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and
      feasible and seems to be an alternative option for patients who have locally
      advanced NSCLC. Surgery may provide additional benefit for patients whose disease
      adequately downstaged after induction chemotherapy.

PMID- 21729650
TI  - Gefitinib as first-line treatment in elderly epidermal growth factor receptor
      mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung
      Cancer Research Group study.
AB  - Efficacy of first-line gefitinib for elderly epidermal growth factor receptor
      mutated patients with lung adenocarcinoma is uncertain. This study was aimed to
      investigate efficacy of gefitinib for such population. The primary endpoint was
      response rate (RR) and at least 12 cases were needed. Overall RR was 59% (95%
      confidence interval, 33%-81%) and first-line gefitinib was effective for elderly
      patients. INTRODUCTION: Feasibility of gefitinib therapy in elderly patients with
      non-small-cell lung cancer is uncertain. This phase II study aimed to investigate
      the efficacy and usefulness of gefitinib therapy as a first-line treatment for
      elderly patients who have advanced lung adenocarcinoma with epidermal growth
      factor receptor (EGFR) mutations. PATIENTS AND METHODS: We enrolled chemotherapy
      naive advanced lung adenocarcinoma patients aged 75 years or older. Patients were
      administered gefitinib (250 mg) once daily until progression or unacceptable
      toxicity. The primary endpoint was response rate (RR), and secondary endpoints
      were disease control rate (DCR; defined as complete response [CR] plus partial
      response [PR] plus stable disease [SD]), progression-free survival (PFS), overall
      survival (OS), and toxicity profile. RESULTS: Between April 2008 and November
      2009, 17 lung adenocarcinoma patients were enrolled. Overall RR was 59% (95%
      confidence interval [CI]: 33% to 81%), with 2 patients achieving CR and 8 PR. SD
      was noted in 5 patients, and DCR was 88% (95% CI: 62% to 98%). Median PFS was
      12.9 months (95% CI: 2.2 to 23.6 months), and median OS had not yet been reached.
      Major grade 3 toxicities were skin rash (12%) and increased levels of aspartate
      aminotransferase or alanine aminotransferase (18%). CONCLUSION: First-line
      treatment with gefitinib was effective and well-tolerated in elderly patients
      with EGFR mutations.

PMID- 21729651
TI  - Analysis of the prognostic value of soluble epidermal growth factor receptor
      plasma concentration in advanced non-small-cell lung cancer patients.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in a variety
      of epithelial malignancies including lung cancer. A soluble fragment of the EGFR
      extracellular domain (sEGFR) can be detected in the blood of patients who have
      non-small-cell lung cancer (NSCLC), but its clinical/ prognostic role must be
      further elucidated. METHODS: sEGFR concentration was retrospectively determined
      by enzyme-linked immunosorbent assay in plasma samples from 308 advanced NSCLC
      patients (before treatment) and 109 healthy controls and correlated with clinico
      pathological variables. RESULTS: The concentration of sEGFR was lower in NSCLC
      patients than in controls (P < .0001). sEGFR behaves as a sensitive but not
      specific screening biomarker. No significant associations were observed between
      sEGFR concentration and demographic/clinical characteristics such as gender,
      Eastern Cooperative Oncology Group performance status, stage, and number or
      location of the metastatic sites. sEGFR was lower in patients with progressive
      disease or in squamous cell carcinoma compared with adenocarcinoma, but these
      differences were not significant. Patients with sEGFR <= 34.56 ng/mL showed a
      shorter overall survival (median 9.1 versus 12.2 months, P = .019) than others.
      Moreover, in multivariate analysis, sEGFR remained a significant independent
      prognostic marker. CONCLUSION: Low baseline sEGFR is associated with reduced
      survival in advanced NSCLC. Therefore, our findings in this large cohort of
      patients suggest that the determination of sEGFR concentration provides valuable
      prognostic information.

PMID- 21729652
TI  - A brief symptom index for advanced lung cancer.
AB  - BACKGROUND: Advanced lung cancer is often symptomatic; thus the goals of
      treatment include maintenance of function and palliation of symptoms. Symptom
      management requires accurate systematic symptom assessment. This study, which
      focused on lung cancer, is part of a larger study to obtain patient input that,
      in combination with previously obtained physician and nurse input, was used to
      develop symptom indexes for 11 advanced cancers. PARTICIPANTS AND METHODS: Fifty
      patients with advanced lung cancer were recruited from National Comprehensive
      Cancer Network (NCCN) member institutions and community support agencies; 10
      physician experts were recruited from NCCN institutions. Patients reported
      symptoms associated with their disease in open-ended format and then completed a
      checklist of symptoms, rating their 5 most important symptoms. Patient and
      provider ratings of symptom importance were tabulated to construct the NCCN
      Functional Assessment of Cancer Therapy (FACT) Lung Symptom Index-17 (NFLSI-17).
      Patients also completed the Functional Assessment of Cancer Therapy-Lung (FACT
      L), which was used to preliminarily validate the NFLSI-17. RESULTS: Based on
      combined patient, physician, and nurse input, the NFLSI-17 is composed of 17
      priority symptoms, 11 that are disease related, 3 that are treatment related, and
      3 that are related to general functional well-being (FWB). Data on 15 of 17 NFLSI
      17 symptoms showed good internal consistency (alpha = 0.74) and strong
      association with the FACT-L total and most subscale scores (r = 0.42-0.92). Both
      the NFLSI-15 (F(2,47) = 4.46; P = .017) and the NFLSI-disease related subscale
      (DRS) (F(2,47) = 5.56; P = .007) significantly discriminated patients among
      performance status groups. CONCLUSION: The NFLSI-17 reflects the most important
      patient- and clinician-rated targets of chemotherapy for advanced lung cancer;
      further validation will follow.

PMID- 21729653
TI  - Circadian aspects of growth hormone-insulin-like growth factor axis function in
      patients with lung cancer.
AB  - BACKGROUND AND PURPOSE: Insulin-like growth factor 1 (IGF1) promotes cell cycle
      progression and inhibition of apoptosis and may have a role in carcinogenesis and
      cancer promotion. Growth hormone (GH) stimulates IGF1 production in liver and
      other tissues. The aim of our study was to evaluate differences between healthy
      subjects and patients with lung cancer in the GH-IGF1 axis function. PATIENTS AND
      METHODS: In 11 healthy male patients (mean age +/- standard error [SE], 43.6 +/-
      1.7), and 9 male patients with non-small-cell lung cancer (mean age +/- SE, 51.0
      +/- 2.4), GH, total IGF1, melatonin, and interleukin (IL)-2 serum levels were
      measured in blood samples collected every 4 hours for 24 hours. RESULTS: A clear
      circadian rhythm was present for melatonin and GH serum levels in the group of
      healthy subjects and for melatonin in the group of patients with cancer. The
      midline estimating statistic of rhythm (MESOR) of GH was higher in patients with
      lung cancer (P < .001), the MESOR of IGF1 was higher in healthy subjects (P <
      .001), the MESOR of melatonin was not different between subjects (P = .383), and
      the MESOR of IL-2 was higher in patients with cancer (P = .02). The GH/IGF1 ratio
      was higher in patients with lung cancer (P = .006). Linear regressions across the
      stages of cancer showed a significant increasing slope for IL-2 (P < .001), GH (P
      < .001), and the GH/IGF1 ratio (P < .001), a decreasing slope for IGF1 (P <
      .001), but no significant trend for melatonin (P = .430). CONCLUSION: There is
      evidence that in patients with lung cancer there is a severe alteration of GH
      IGF1 axis function, with loss of circadian rhythmicity of hormone secretion,
      which may play a role in the progression of neoplastic disease and must be
      considered in defining the therapeutic approach.

PMID- 21729654
TI  - Small-cell lung cancer in never-smokers: a case series with information on family
      history of cancer and environmental tobacco smoke.

PMID- 21729655
TI  - EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic
      lesions: discordance in pleural metastases.
AB  - We evaluated EGFR and KRAS mutations between 37 paired primary tumors and
      corresponding metastases in lung adenocarcinoma. A substantial discordance was
      found in EGFR mutation status between primary tumors and corresponding metastases
      including pleural metastases. Moreover, the responsiveness to EGFR tyrosine
      kinase inhibitors tend to be correlated with EGFR mutation status in metastatic
      lesions than in primary tumors. INTRODUCTION: The aim of this study was to
      compare epidermal growth factor receptor (EGFR) and KRAS mutations between
      primary tumors and corresponding metastases including pleural metastases in lung
      adenocarcinoma. METHODS: Thirty-seven paired primary lung adenocarcinomas and
      corresponding metastatic tumors were analyzed for EGFR and KRAS mutations. In
      addition, 21 pleural metastases including malignant pleural effusion or pleural
      biopsy were used in performing these mutation analyses. RESULTS: EGFR mutations
      were detected in 18 primary lung adenocarcinomas (48.6%) and in 16 corresponding
      metastases (43.2%). EGFR mutations showed a discordance rate of 16.2% (6 of 37
      patients) between primary lung adenocarcinomas and corresponding metastases.
      Among 21 pleural metastases, 3 patients (14.3%) showed that the EGFR mutation was
      discordant. KRAS mutations were detected in one primary tumor and in two
      metastatic tumors. Eighteen patients were treated with EGFR tyrosine kinase
      inhibitors. One of seven patients who experienced partial response had EGFR
      mutations only in the metastasis, and two of seven patients who experienced
      progressive disease carried wild-type EGFR only in the metastasis. CONCLUSIONS:
      EGFR mutations were discordant between primary tumors and corresponding
      metastases in a significant portion of lung adenocarcinomas. Furthermore, these
      discordance was also observed in metastases to the pleura, the nearest metastatic
      site.

PMID- 21729656
TI  - Consensus statement on palliative lung radiotherapy: third international
      consensus workshop on palliative radiotherapy and symptom control.
AB  - The purpose of this work is to disseminate a consensus statement on palliative
      radiotherapy (RT) of lung cancer created in conjunction with the Third
      International Lung Cancer Consensus Workshop. The palliative lung RT workshop
      committee agreed on 5 questions relating to (1) patient selection, (2) thoracic
      external-beam radiation therapy (XRT) fractionation, (3) endobronchial
      brachytherapy (EBB), (4) concurrent chemotherapy (CC), and (5) palliative
      endpoint definitions. A PubMed search for primary/cross-referenced practice
      guidelines, consensus statements, meta-analyses, and/or systematic reviews was
      conducted. Final consensus statements were created after review and discussion of
      the available evidence. The following summary statements reflect the consensus of
      the international working group. 1. Key factors involved in the decision to
      deliver palliative RT include performance status, tumor stage, pulmonary
      function, XRT volume, symptomatology, weight loss, and patient preference. 2.
      Palliative thoracic XRT is generally indicated for patients with stage IV disease
      with current/impending symptoms and for patients with stage III disease treated
      for palliative intent. 3. There is no evidence to routinely recommend EBB alone
      or in conjunction with other palliative maneuvers in the initial palliative
      management of endobronchial obstruction resulting from lung cancer. 4. There is
      currently no evidence to routinely recommend CC with palliative-intent RT. 5.
      Standard assessment of symptoms and health-related quality of life (QOL) using
      validated questionnaires should be carried out in palliative RT lung cancer
      trials. Despite an expanding literature, continued prospective randomized
      investigations to better define the role of XRT, EBB, and CC in the context of
      thoracic palliation of patients with lung cancer is needed.

PMID- 21729657
TI  - Osteonecrosis of the jaw: dental outcomes in metastatic breast cancer patients
      treated with bisphosphonates with/without bevacizumab.
AB  - The etiology, optimal management, and outcome of osteonecrosis of the jaw (ONJ)
      are not well understood. Because healing after mucosal trauma requires
      revascularization, theoretically, the combination of bevacizumab (bev) and a
      bisphosphonate (BP) could affect the time to development of ONJ and/or the
      response to dental therapy. We reviewed all cases of ONJ in metastatic breast
      cancer patients treated at our institution with bev+BPs and BPs alone between
      October 2002 and April 2010. We identified 27 ONJ patients with a median age of
      57 years (range, 40 to 68 years). Seven patients received bev+BPs; 20 patients
      received BPs alone. Patients received intravenous zolendronate (95%), pamidronate
      (20%), or both (15%). Patients were treated with antibiotics (93%),
      alveoplasty/debridement (67%), and chlorhexidine scrub (81%). There was no
      difference in dental treatment between the groups or by the year of diagnosis
      (before 2007 versus 2007-2010). Complete resolution (CR) was achieved in 24% of
      all patients; 33% treated with bev+BPs, and 21% treated with BPs alone. Rates of
      CR improved from 15% to 33% after 2007. The median time to response was 5.6
      months (range, 1.3 to 67.5 months). The addition of bev to BPs did not appear to
      alter the time to development of ONJ (32.6 months versus 34.6 months,
      respectively). The number of BP treatments administered before the diagnosis of
      ONJ between bev+BPs and BPs (32 doses versus 36.5 doses) was similar. However,
      our sample size was too small to characterize the difference statistically.
      Because dental management of ONJ has not changed over time at our institute,
      early recognition and screening may account for the improvement in dental
      outcomes.

PMID- 21729658
TI  - Fulvestrant revisited: efficacy and safety of the 500-mg dose.
AB  - Postmenopausal women with hormone receptor-positive advanced breast cancer are
      candidates for endocrine therapy. As the disease will eventually progress in most
      patients, it is important to investigate agents with novel modes of action to
      reduce the likelihood of treatment cross-resistance. Fulvestrant is an estrogen
      receptor antagonist with no known agonist effects that has been shown to be as
      effective as anastrozole following failure on tamoxifen, at the approved dose of
      250 mg/mo. However, pharmacokinetic modelling and evidence of clinical efficacy
      in early trials, together with the favorable tolerability profile of fulvestrant
      250 mg, led to suggestions that increasing the fulvestrant dose would lead to an
      improved benefit-risk profile. This review describes the rationale behind the
      development of a 500 mg/mo higher dose of fulvestrant and details relevant
      clinical trials, including the pivotal phase III COmparisoN of Faslodex In
      Recurrent or Metastatic breast cancer (CONFIRM) study. CONFIRM demonstrated a
      significant improvement in progression-free survival for fulvestrant 500 mg
      versus 250 mg in postmenopausal patients who had progressed on previous endocrine
      therapy. Here, we present and discuss a pooled safety analysis of CONFIRM and
      three further clinical studies demonstrating fulvestrant 500 mg to be well
      tolerated with no evidence of dose-related adverse events. Overall, these data
      indicate an improved benefit-risk profile for fulvestrant 500 mg versus 250 mg
      following failure on prior endocrine therapy, and suggest that fulvestrant 500 mg
      may be considered in future as initial endocrine treatment for advanced breast
      cancer.

PMID- 21729659
TI  - Nipple discharge after nipple-sparing mastectomy: should the areola complex
      always be removed?
AB  - Nipple discharge (ND) is a common symptom with a reported incidence of 2% to 5%
      of patients referred to breast cancer clinics. Approximately 90% of ND is of
      benign etiology. An underlying carcinoma is present with a rate of 6% to 21%.
      This is more frequent if it is associated with clinical or radiologic
      abnormality. ND after nipple-sparing mastectomy (NSM) is a rare event as the
      whole retroareolar glandular tissue is usually completely removed with
      mastectomy. ND is otherwise possible if a small amount of tissue is accidentally
      left by the surgeon or with the aim of reducing the risk of the nipple-areola
      complex (NAC) necrosis. This condition can be of concern as it may imply a local
      recurrence and therefore implicate NAC removal. Herein we report a case of a ND
      in an NSM in which only a selective duct excision allowed NAC preservation.

PMID- 21729660
TI  - Development of breast cancer in a 21-year-old childhood Wilms' tumor survivor
      with a BRCA1 2634delC mutation.
AB  - Breast cancer at age 21 is rare, even in individuals who have a genetic
      predisposition. These early diagnoses are usually the result of a hereditary
      cancer syndrome. Other contributing factors, such as chemotherapy and radiation
      for previous malignancies, can also increase the risk of secondary malignancies,
      including breast cancer. Here we present one of the youngest cases of breast
      cancer reported in the literature: a 21-year-old Wilms' tumor survivor (diagnosed
      at age 6), who was found to have a familial BRCA1 mutation and was diagnosed with
      ductal carcinoma in situ at age 21.

PMID- 21729661
TI  - Trastuzumab emtansine (T-DM1): a novel agent for targeting HER2+ breast cancer.
AB  - Increased understanding of the molecular mechanisms of tumorigenesis has led to
      the development of novel agents that target tumor cells with minimal effects on
      normal cells. The success of this approach is exemplified by the development of
      monoclonal antibodies directed toward antigens expressed selectively by tumor
      cells. The conjugation of these monoclonal antibodies with potent cytotoxic drugs
      has the potential to further improve efficacy while retaining a favorable safety
      profile. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC)
      currently in clinical development. It combines the humanized antibody
      trastuzumab, which targets the human epidermal growth factor receptor 2 (HER2)
      receptor on cancer cells, and the potent antimicrotubule agent DM1 using a unique
      highly stable linker. When T-DM1 binds to HER2, a proportion of the receptors are
      thought to be internalized by the process of receptor endocytosis, followed by
      the intracellular release of an active form of DM1, which in turn kills the tumor
      cell. This review presents the rationale for the development of T-DM1 and
      summarizes the preclinical and clinical data for this novel agent for the
      treatment of breast cancer.

PMID- 21729662
TI  - Early and more advanced unifocal and multifocal breast carcinomas and their
      molecular phenotypes.
AB  - BACKGROUND: I examined the relationship between the recently established
      prognostic parameter, molecular tumor phenotype and tumor size, lesion
      distribution (unifocal, multifocal, diffuse growth), and lymph node status.
      MATERIALS AND METHODS: I analyzed 660 consecutive invasive breast carcinomas
      documented in large-format histology sections. Immunohistochemistry was used to
      phenotype the tumors on the basis of estrogen and progesterone receptor
      expression, HER2 (human epithelial growth factor receptor 2) overexpression, and
      expression of basal markers. RESULTS: The proportion of luminal A tumors (84.8%
      vs. 71.6%; P < .0001) and basal-like tumors (5.0% vs. 14.8%; P < .0001) were
      significantly different in early (<15 mm) and more advanced invasive breast
      carcinomas, whereas the proportion of luminal B and HER2 type tumors (4.2% vs.
      7.8%, and 5.7% vs. 4.8%, respectively) were not. All the phenotypes had similar
      percentages of multifocal tumors, whereas most diffuse invasive carcinomas were
      luminal A type. Early luminal A carcinomas had significantly fewer lymph node
      metastases (LNM) than more advanced carcinomas but luminal B and HER2 type tumors
      showed no such difference. This difference was evident (15.4% vs. 42.4%) but
      statistically not significant in the basal-like category. Multifocal tumors of
      all phenotypes had significantly higher frequencies of LNM compared with unifocal
      tumors. CONCLUSION: Multifocality of the invasive component represents a negative
      prognostic parameter associated with significantly increased LNM in all
      phenotype, whereas larger tumor size was such a parameter only in the luminal A
      category. HER2 overexpression occurs early in the natural history of tumors and
      is associated with high LNM rates.

PMID- 21729663
TI  - Fulvestrant high dose vs. loading dose vs. approved dose: have we found the
      optimum dose?

PMID- 21729664
TI  - Effective role of hormonal therapy in metastatic primary neuroendocrine breast
      carcinoma.
AB  - Primary neuroendocrine carcinoma (PNEC) of the breast is extremely rare.(1)
      Because of the rarity of this cancer, long-term prognosis, biologic behavior, and
      treatment are not well known. PNEC can have high expression of estrogen receptor
      (ER) and progesterone receptor (PR). It is important to differentiate PNEC of the
      breast from other metastatic diseases to the breast because of the differences in
      treatment. We herein report the successful treatment of a patient with PNEC of
      the breast and high expression of ER and PR by means of hormonal therapy.

PMID- 21729665
TI  - ALK-1-negative anaplastic large cell lymphoma associated with breast implants: a
      new clinical entity.
AB  - Concerns have been raised recently regarding the increasing number of reports of
      non-Hodgkin lymphoma (NHL) that developed in close proximity to silicone or
      saline breast implants. In particular, an increased risk of anaplastic large cell
      lymphoma (ALCL) in patients with breast prostheses has been proposed. We reviewed
      clinical and pathologic findings in 40 women who received a diagnosis of breast
      NHL arising in association with breast implants and of 27 patients who had a
      diagnosis of ALCL with breast involvement reported in the published literature.
      Among the 40 reported cases of prosthesis-associated breast lymphomas, 28 were
      anaplastic lymphoma kinase-1-negative (ALK-1(-)) ALCLs, whereas of 27 ALCLs in
      patients without implants found in the literature, only 10 were ALK-1(-). The
      finding of 28 cases of breast ALK-1(-) ALCL occurring in patients with implants
      compared with 10 cases in women without implants is in favor of an association
      between silicone breast prostheses and ALK-1(-) ALCL. Although the incidence of
      this type of lymphoma remains remarkably low given that breast prostheses have
      been widely used for decades, clinical and pathologic evidence for a causative
      role is becoming dramatically strong. The histologic, phenomenologic, and
      clinical similarities of the majority of implant-related ALK-1(-) ALCLs suggest a
      common mechanism, especially when compared with the counterpart of patients
      without implants in which very few and highly dishomogeneous cases of the same
      malignancy were detected. There is convincing evidence that primary implant
      related ALK-1(-) ALCL represents a distinct clinicopathologic entity that has
      been inappropriately fitted into the category of systemic ALK-1(-) ALCL. Thus it
      should be recognized as a separate category and classified on its own.

PMID- 21729666
TI  - Phase II study of neoadjuvant weekly nab-paclitaxel and carboplatin, with
      bevacizumab and trastuzumab, as treatment for women with locally advanced HER2+
      breast cancer.
AB  - PURPOSE: Neoadjuvant treatment with chemotherapy plus trastuzumab is standard
      care for women with locally advanced, HER2-positive (HER2(+)) breast cancer. HER2
      has been shown to stimulate angiogenesis through vascular endothelial growth
      factor upregulation. We investigated the feasibility and efficacy of bevacizumab
      in combination with trastuzumab, nab-paclitaxel, and carboplatin as neoadjuvant
      therapy for women with locally advanced HER2(+) breast cancer. PATIENTS AND
      METHODS: Twenty-eight women with locally advanced HER2(+) breast cancer received
      nab-paclitaxel (100 mg/m(2) intravenously [I.V.] days 1,8, and 15) and
      carboplatin (AUC = 6 I.V. day 1) every 28 days * 6 cycles. Concurrent with
      chemotherapy, trastuzumab (4 mg/kg loading dose, then 2 mg/kg) and bevacizumab (5
      mg/kg I.V.) were administered weekly * 23 weeks. Patients then underwent
      mastectomy or breast-conserving surgery; pathologic responses were assessed.
      After surgery, trastuzumab 6 mg/kg and bevacizumab 15 mg/kg were administered
      every 3 weeks (54 weeks total); locoregional radiotherapy and/or antiestrogen
      therapy was administered per standard guidelines. RESULTS: Twenty-six patients
      (90%) completed neoadjuvant therapy, with objective responses in 86%. Pathologic
      complete response (pCR) was confirmed in 14 of the 26 patients (54%) who had
      surgery. However, bevacizumab-related complications were common postoperatively
      and during adjuvant trastuzumab/bevacizumab therapy. Ten patients had wound
      healing delays or infections (6 patients discontinued therapy); 4 patients had
      left ventricular ejection fraction (LVEF) decreases (1 patient discontinued
      therapy). Other severe treatment-related toxicity was uncommon. Only 9 patients
      (31%) completed all protocol therapy. CONCLUSIONS: Neoadjuvant therapy with nab
      paclitaxel, carboplatin, trastuzumab, and bevacizumab was feasible in most
      patients, producing a pCR rate comparable to that in chemotherapy/trastuzumab
      combinations. In contrast, prolonged bevacizumab/trastuzumab therapy after
      surgical treatment was not well tolerated, primarily due to bevacizumab-related
      toxicity. The role of bevacizumab in neoadjuvant therapy remains undefined.

PMID- 21729667
TI  - Phase II trial of saracatinib (AZD0530), an oral SRC-inhibitor for the treatment
      of patients with hormone receptor-negative metastatic breast cancer.
AB  - BACKGROUND: SRC activation is associated with cell migration, proliferation, and
      metastasis. Saracatinib is an oral tyrosine kinase inhibitor (TKI) selective for
      SRC. We performed this trial to evaluate the efficacy and safety of saracatinib
      monotherapy in patients with estrogen receptor (ER)(-) and progesterone receptor
      (PR)(-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients who had
      undergone <= 1 previous chemotherapy regimen for measurable ER(-) and PR(-) MBC
      received saracatinib 175 mg orally daily. The primary endpoint was disease
      control defined as complete response (CR) + partial response (PR) + stable
      disease (SD) > 6 months. Secondary endpoints included toxicity and progression
      free survival (PFS). Levels of circulating tumor cells (CTCs) in response to
      therapy were measured over time. RESULTS: Nine patients were treated on study.
      After a median of 2 cycles (range 1-3), no patient had achieved CR, PR, or SD >6
      months. The median time to treatment failure was 82 days (12-109 days).The
      majority (89%) of patients discontinued saracatinib because of disease
      progression. One patient acquired potentially treatment-related grade 4 hypoxia
      with interstitial infiltrates and was removed from the study. Common adverse
      events included fatigue, elevated liver enzymes, nausea, hyponatremia, dyspnea,
      cough, and adrenal insufficiency. CONCLUSIONS: These efficacy results were not
      sufficiently promising to justify continued accrual to this study. Based on this
      series, saracatinib does not appear to have significant single-agent activity for
      the treatment of patients with ER(-)/PR(-) MBC.

PMID- 21729668
TI  - Chylous fistula after axillary lymph node dissection: incidence, management, and
      possible cause.
AB  - INTRODUCTION: Chylous fistula is a known complication in procedures such as neck
      dissection and aneurysm surgery. However chyle leak that develops after axillary
      dissection is a rare phenomenon. In this study we have evaluated the incidence,
      possible cause, and management of chylous fistula that develops after radical
      breast cancer surgeries. MATERIAL AND METHODS: Chylous fistula developed in 6 of
      1863 patients who underwent axillary dissection. Their records were analyzed in
      terms of clinical profile and management. A review of the literature regarding
      the thoracic duct anatomy at its termination was carried out and a hypothesis
      about the possible cause of chylous leak was suggested. RESULTS: All 6 patients
      had procedures on the left side and had varied clinical stages and profiles. The
      chyle discharge was detected intraoperatively during the primary surgical
      procedure in 2 patients. The other 4 patients presented with chyle in their
      drains postoperatively. One patient did not respond to conservative management
      and underwent reexploration to seal the leak. Injury to the thoracic duct or its
      aberrant branches is apparently not the cause of chylous fistula in the axilla.
      The injury to the left subclavian duct or its tributary, which drains aberrantly
      into the thoracic duct through a valveless junction has been hypothesized to be
      the source of chyle in the axilla. CONCLUSION: Chylous fistula is very unusual
      after axillary dissection. Most of the chyle leaks in the axilla are manageable
      through conservative methods; surgical intervention is required rarely in special
      situations. Injury to the left subclavian duct or its tributary is the possible
      cause.

PMID- 21729669
TI  - Breast lymphoma complicating anti-tumor necrosis factor therapy in rheumatoid
      arthritis.
AB  - The relationship between anti-TNF therapy and development of lymphoma in
      Rheumatoid arthritis (RA) patients is controversial. However lymphomas of unusual
      types and sites have been reported among RA patients receiving anti-TNF therapy.
      Primary lymphoma of the breast is a rare entity and has never been reported to
      occur among RA patients taking anti-TNF therapy. This is the first case of
      primary lymphoma of the breast reported among RA patients on anti-TNF therapy.
      Rheumatoid arthritis patients currently on anti-TNF therapy should undergo
      routine gynecological examination.

PMID- 21729670
TI  - Prevalence and prognostic role of triple-negative breast cancer by race: a
      surveillance study.
AB  - INTRODUCTION: Emerging research suggests a substantially greater prevalence of
      the adverse triple-negative (TN) subtype (human epidermal growth factor receptor
      [HER]2(-), estrogen receptor [ER](-), and progesterone receptor [PR])(-)) among
      black patients with breast cancer. No reports however have been generated from a
      statewide cancer registry. PATIENTS AND METHODS: The study consisted of all black
      patients (N = 643) and a random sample of white patients (n = 719) diagnosed with
      primary invasive breast cancer (2000-2003) listed in the National Cancer
      Institute-Surveillance Epidemiology and End Results (NCI-SEER) Connecticut Tumor
      Registry (CTR). HER2 status was obtained from pathology reports submitted to the
      registry. Remaining data were obtained from the registry database. RESULTS: TN
      tumors were more prevalent in black compared with white patients (30.8% vs.
      11.2%, respectively; P < .001.) There was a 2-fold greater frequency of ER(-) and
      PR(-) phenotypes among black patients, but HER2 status did not differ by race.
      Patients with lobular cancer were less likely to have TN breast cancer compared
      with patients with ductal tumors (odds ratio [OR] = 0.23; 95% confidence interval
      [CI], 0.10-0.58). Among patients with regional disease, black patients exhibited
      increased risk of death (relative risk [RR] = 2.71; 95% CI, 1.48-4.97)
      independent of TN status. No survival disparity was found among patients with
      local disease. DISCUSSION: These registry-based data corroborate reports that TN
      breast cancer varies substantially by race and histologic subtype. A survival
      disparity among patients with advanced disease, but not local disease, casts some
      doubt on TN status as an explanation for differences. CONCLUSION: More research
      is warranted to understand why black patients with advanced breast cancer may be
      at increased risk for death whether or not their tumors express the TN phenotype.

PMID- 21729671
TI  - Phase II trial of neoadjuvant exemestane in combination with celecoxib in
      postmenopausal women who have breast cancer.
AB  - PURPOSE: Within breast tissue, aromatase expression and activity is increased by
      prostaglandin E2, providing a rationale for combining the COX-2 inhibitor
      celecoxib with an aromatase inhibitor. To evaluate the effect of these drugs on
      aromatase and other biomarkers, a phase II trial of neoadjuvant exemestane
      followed sequentially by celecoxib plus exemestane was performed. METHODS:
      Postmenopausal women with estrogen receptor (ER) and/or progesterone (PR)
      positive stages II-III breast cancers received 8 weeks of exemestane 25 mg daily,
      followed by 8 weeks of exemestane 25 mg daily and celecoxib 400 mg twice daily.
      Core biopsies were collected pretreatment, after 8 weeks of exemestane, and at
      definitive breast cancer surgery. A tissue microarray was constructed and
      immunohistochemistry (IHC) for aromatase, ER, PR, HER-2, Ki-67, and COX-2 was
      performed. RESULTS: Twenty-two women were enrolled. Celecoxib was discontinued in
      4 (18%) women for toxicity (all grade 1 and 2) and 2 (9%) developed serious
      cardiac events occurring at 1 and 4 months after completing treatment. By US,
      there were 8 (36%)-partial responses and 12 (55%)-stable disease. There were no
      pathological complete responses (pCR). There were statistically significant
      decreases in ER (P = .003), PR (P = .002), Ki-67 (P < .001), and COX-2 (P = .004)
      expression. No significant differences in aromatase or HER-2 expression were
      observed (P = .13 and P = .39, respectively). CONCLUSION: The addition of
      celecoxib to exemestane was tolerated by the majority of women and anti-tumor
      response was observed. Additional studies, including gene expression, are
      required to more fully understand the basis for the decreased expression of ER,
      PR, Ki-67, and COX-2.

PMID- 21729672
TI  - Giant lipoma of the breast: a case report and review of the literature.

PMID- 21729673
TI  - Partial breast irradiation delivered with proton beam: results of a phase II
      trial.
AB  - BACKGROUND AND PURPOSE: A phase II trial sought to determine the safety and
      efficacy of proton beam irradiation to deliver partial breast radiotherapy after
      lumpectomy for early-stage breast cancer. PATIENTS AND METHODS: Eligible patients
      included women with invasive nonlobular carcinoma <= 3 cm. Surgical therapy
      included lumpectomy with negative margins and negative axillary lymph nodes on
      sampling. Postoperative proton radiotherapy to the surgical bed with an
      additional 1-cm margin was delivered by 40 Gy in 10 fractions over a 2-week
      course. Patients received systemic therapy as recommended after proton treatment.
      Patients had clinical evaluations every 6 months and annual mammograms. RESULTS:
      Fifty patients were enrolled; median follow-up was 48 months. All patients
      completed the prescribed treatment. Acute toxicities were limited to mild
      radiation dermatitis. Late skin toxicities included 3 grade 1 telangiectasias.
      There were no posttreatment infections or ulcerations and no cases of fat
      necrosis, rib fractures, radiation pneumonitis, or cardiac events. Actuarial 5
      year overall survival and disease-free survival rates were 96% and 92%,
      respectively. No local failures occurred. Ipsilateral breast cancer developed in
      1 patient 5.5 years after treatment. Dose-volume histogram analysis showed near
      complete elimination of dose to the contralateral breast, lung, and heart.
      CONCLUSION: Proton partial breast radiotherapy appeared to be a feasible method
      of treatment and provided excellent disease control within the ipsilateral
      breast. Treatment-related toxicity was minimal and no technical limitations
      prevented treatment delivery. The incidence of posttreatment complications may be
      less than that reported when using more invasive techniques; comparative trials
      should be considered.

PMID- 21729674
TI  - Impact of race on colorectal cancer.
AB  - BACKGROUND: Several studies have shown that colorectal cancer runs a more severe
      course in blacks compared with whites. Black patients tend to have more advanced
      disease at diagnosis and are more likely to die of cancer than are white
      patients. The present study was carried out to compare the characteristics and
      outcomes of colon cancer in blacks and whites in a Veterans Affairs Medical
      Center, where patients are expected to receive similar treatment irrespective of
      race. METHODS: The database of the Veterans Affairs Medical Center was searched
      for all patients with a histologic diagnosis of colon cancer diagnosed since
      1996. Detailed information on patient and tumor characteristics was obtained. In
      addition the type of treatment and outcome was analyzed. RESULTS: A total of 300
      subjects were included in the study. They comprised 205 white and 95 black
      patients. There was no difference in age at presentation between the 2 groups.
      Blacks were more likely to have anemia (P = .005) and rectal bleeding (P < .001)
      than were whites. However there was no difference between the 2 groups with
      respect to the histologic grade of the tumor, the extent of disease at
      presentation, the proportion of patients receiving curative surgery, and the time
      to death after diagnosis. CONCLUSIONS: There was no racial difference in the
      treatment outcome of colon cancer in patients treated at a Veterans Affairs
      Medical Center. These findings indicate that if patients receive similar
      treatment, the racial background of an individual does not have any impact on the
      severity of disease at presentation and the outcome of treatment.

PMID- 21729675
TI  - Integration of biologic agents with cytotoxic chemotherapy in metastatic
      colorectal cancer.
AB  - Colorectal cancer (CRC) remains a leading cause of cancer death in the developed
      world. Metastatic disease eventually develops in nearly 50% of patients with CRC.
      Chemotherapy is the mainstay of treatment in metastatic CRC (mCRC); however the
      majority of patients remain incurable with current therapeutic options. Progress
      made in the field of surgery, locoregional treatment for low-volume metastatic
      disease, and systemic chemotherapy has created new treatment paradigms and
      improved survival in mCRC. Development of new cytotoxic drugs and the advent of
      targeted agents over the past decade have seen the median overall survival (OS)
      for mCRC increase from 9 months to > 2 years. Data from trials integrating
      targeted therapies appear to indicate that not all have efficacy as single agents
      and the choice of chemotherapy used in combination with these agents may impact
      results. Ongoing research is leading to identification of new biomarkers of
      response, further defining the subpopulations who achieve greatest benefit. Hence
      optimizing treatment for this group of patients has become increasingly complex,
      requiring a multidisciplinary approach not only to identify those who are curable
      with resectable disease but also to determine when it is best to incorporate
      targeted drugs, with which chemotherapy, and in whom. Currently bevacizumab,
      cetuximab, and panitumumab are the only approved biologic agents for use in mCRC.
      In this article we discuss the evidence supporting the use of biologic agents
      with chemotherapy and suggested strategies for their integration into the
      treatment armamentarium of mCRC.

PMID- 21729676
TI  - Analysis for prognostic factors of 60-day mortality: evaluation of an irinotecan
      based phase III trial performed in the first-line treatment of metastatic
      colorectal cancer.
AB  - BACKGROUND: Mortality rates in published irinotecan-based trials range between
      1.7% and 5.0%. This analysis aimed to evaluate clinical and histopathologic
      factors associated with 60-day mortality in first-line therapy for metastatic
      colorectal cancer (mCRC). PATIENTS AND METHODS: Sixty-day all-cause and disease
      specific mortality rates from 479 patients who participated in a randomized phase
      III study comparing FUFIRI (5-fluorouracil [5-FU], leucovorin, irinotecan) (n =
      238) vs. mIROX (modified irinotecan plus oxaliplatin (n = 241) were evaluated for
      association with prognostic factors such as platelet counts, alkaline phosphatase
      (AP) levels, white blood cell (WBC) counts, hemoglobin values, lactate
      dehydrogenase (LDH) levels, carcinoembryonic antigen (CEA) levels, and several
      other baseline parameters using univariate and multivariate logistic regression
      analyses applied to patients combined from both treatment groups. RESULTS: The
      all-cause 60-day mortality rate was 5.0% (24/479). Thirteen patients (5.5%) in
      the FUFIRI arm died within the first 60 days of treatment compared with 11 (4.6%)
      patients in the mIROX arm (P = .68). Among the 24 patients in both treatment
      arms, mortality was qualified as disease related in 15 (63%) patients and
      treatment related in 7 (29%) patients (P = .695). In multivariate analyses, high
      LDH levels (P = .010) and an elevated WBC count (P = .006) remained as
      significant independent prognostic factors. Low Karnofsky performance status
      (KPS) showed a strong trend but failed to reach statistical significance (P =
      .057) as did AP levels and the number of metastatic sites. CONCLUSION: In this
      study 63% of the early deaths were disease related, whereas only 29% were
      possibly related to study medication. Independent prognostic factors for early
      mortality were LDH levels and WBC counts. KPS showed a strong trend in the
      multivariate analysis. Future investigation may consider LDH levels and WBC
      counts for exclusion criteria.

PMID- 21729677
TI  - Is there a role for IGF1R and c-MET pathways in resistance to cetuximab in
      metastatic colorectal cancer?
AB  - BACKGROUND: The KRAS mutation is not responsible for all cases of resistance to
      anti-epidermal growth factor receptors (EGFRs) in metastatic colorectal cancer
      (mCRC), and new predictive and prognostic factors are actively being sought.
      PATIENTS AND METHODS: We retrospectively evaluated the efficacy of a cetuximab
      containing treatment in 73 patients with mCRC according to KRAS and BRAF
      mutational status as well as PTEN, c-MET, and insulin-like growth factor receptor
      (IGF1R) expression. RESULTS: Overall response rate (ORR), median progression-free
      survival (mPFS), and median overall survival (mOS) were significantly lower in
      patients with KRAS mutation than in patients with KRAS wild-type; among the
      population with KRAS wild-type, only 2 patients with BRAF mutations were found
      and neither of them achieved a response. No significant association was found
      between PTEN and clinical outcome. Compared with low/normal expression, c-MET
      overexpression significantly correlated with shorter mPFS and mOS: 3 vs. 5 months
      (P = .018) and 11 vs. 10 months (P = .037), respectively. In patients with high
      IGF1R expression, mOS was significantly longer than in those with low/normal
      expression (14 vs. 8 months; P = .015). CONCLUSION: KRAS mutation significantly
      correlates with a worse outcome in patients treated with cetuximab, whereas no
      definitive inference can be drawn about the role of BRAF mutation and PTEN loss
      of expression. Instead, c-MET overexpression might represent a negative
      prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy.
      Interestingly, IGF1R overexpression seems a favorable prognostic factor in mCRC.

PMID- 21729678
TI  - Hepatic arterial infusion and systemic chemotherapy after multiple metastasectomy
      in patients with colorectal carcinoma metastatic to the liver: a North Central
      Cancer Treatment Group (NCCTG) phase II study, 92-46-52.
AB  - BACKGROUND: Patients with multiple liver metastases from colorectal cancer are at
      high risk of recurrence after resection. Hepatic artery infusion (HAI)
      alternating with systemic therapy after surgical resection may improve survival
      after surgery. METHODS: Patients with liver-only metastases from colorectal
      cancer amenable to resection/cryoablation were eligible. Previous adjuvant
      chemotherapy for a completely resected primary tumor was allowed. Alternating
      courses of HAI and systemic therapy included floxuridine (FUDR) by HAI. Systemic
      chemotherapy consisted of bolus leucovorin (LV) plus 5-fluorouracil (5-FU).
      RESULTS: Forty-nine patients had complete resection of their liver metastases,
      with 44% having more than 4 hepatic metastases and 78% having bilobar disease.
      Thirty-six patients had HAI FUDR alternating with systemic therapy. Patients
      received a median of 3.5 cycles (range, 1-4) and 3 cycles (range, 0-6) of therapy
      with HAI FUDR and systemic therapy, respectively. At the time of final analysis
      the estimated median disease-free survival and hepatic disease-free survival was
      1.2 years (95% confidence interval [CI], 0.9-2.1) and 1.8 years (95% CI, 1.8-not
      available), respectively. Eleven patients (31%) were alive at this writing. All
      surviving patients had a minimum of 5.5 years of follow-up. CONCLUSION: This
      trial of adjuvant chemotherapy in patients who underwent complete resection with
      unfavorable characteristics demonstrates apparent improvement in outcome compared
      with historical series treated with surgery alone. However the results of this
      trial and other randomized trials of HAI do not appear to support its use at this
      time because of the development of more effective systemic options.

PMID- 21729679
TI  - Development of molecular biomarkers in individualized treatment of colorectal
      cancer.
AB  - Colorectal cancer is a leading cause of cancer mortality despite recent expansion
      of treatment options in metastatic colorectal cancer (mCRC). Our knowledge about
      key signaling pathways in colorectal tumors has contributed to the identification
      of specific molecular markers of response to targeted agents. In this review we
      discuss well-established and potential predictive biomarkers of benefit with
      epidermal growth factor receptor (EGFR) inhibitors. Data derived from multiple
      phase III trials have indicated that KRAS mutations can be considered a highly
      specific negative biomarker of response to anti-EGFR monoclonal antibodies. Other
      molecular aberrations in pathways downstream of EGFR such as BRAF, NRAS, and
      PIK3CA mutations, and PTEN loss are also reviewed. Moreover biomarkers of
      efficacy to classic chemotherapeutic agents as well as recent advances regarding
      high-throughput technologies and circulating tumor cells are also considered.
      Personalized cancer medicine in the mCRC scenario seems to be near reality, but
      validation of many biomarkers in prospective clinical trials is urgently
      warranted.

PMID- 21729680
TI  - Sunitinib-induced acute psychosis: case report.

PMID- 21729681
TI  - Primary primitive neuroectodermal tumor of the bladder: histologic and clinical
      features of 9 cases.

PMID- 21729682
TI  - Zosteriform rash: another manifestation of "the internist's tumor".

PMID- 21729683
TI  - A prospective study of cognitive complaints in patients with testicular cancer.
AB  - Self-reported memory and concentration problems (cognitive complaints) among
      testicular cancer patients treated with chemotherapy or radiotherapy during the
      1990-ies were prospectively explored. The chemotherapy group had significantly
      higher prevalence of cognitive complaints compared to the radiotherapy group at 3
      months follow-up, while at 12-months no significant group difference was found.
      Treatment modality (chemotherapy vs. radiotherapy) was not significantly
      associated with the presence of cognitive complaints at any time point after
      adjustment for relevant QoL variables. INTRODUCTION: Cognitive complaints are
      frequent among patients with cancer. Oncologists and patients have become
      concerned that systemic chemotherapy may have cognitive side effects. After this
      concern became public there was a risk of expectation bias in studies of
      cognitive complaints. We prospectively explored cognitive complaints in patients
      with testicular cancer treated with chemotherapy or radiotherapy during the
      1990s, before today's increased awareness of this possible side effect. PATIENTS
      AND METHODS: The European Organisation for Research and Treatment of Cancer
      (EORTC) quality of life (QoL) questionnaire (QLQ-C30) and a testicular cancer
      module (TC module) were completed before treatment (baseline), at 3 months, and
      at 12 months by 276 chemotherapy and 71 radiotherapy patients enrolled in 3 EORTC
      studies. Cognitive complaints were based on the cognitive function (CF) items
      (concentration and memory) of the QLQ-C30. Other QLQ-C30 functions and symptoms
      represented adjustment variables. RESULTS: The chemotherapy group (CHEMO) showed
      a significant increase in prevalence of cognitive complaints from baseline to 3
      months. At 12 months these rates were back at baseline levels. The radiotherapy
      group (RAD) showed no significant change in the prevalence of cognitive
      complaints over time. Significant differences between the 2 treatment groups were
      observed only at the 3-month follow-up. In multivariate analyses, treatment
      modality did not show significant association with cognitive complaints at any
      time point, whereas current fatigue showed significant associations at all time
      points. CONCLUSION: In patients with testicular cancer with no information or
      expectation bias, an increased rate of cognitive complaints was observed shortly
      after chemotherapy, with return to baseline levels at 12 months. Treatment
      modality (chemotherapy vs. radiotherapy) was not associated with cognitive
      complaints at any time point after adjustment for relevant QoL variables.

PMID- 21729684
TI  - Prolonged remission of fulminant castrate-resistant prostate cancer: a case
      report.

PMID- 21729685
TI  - Rapidly fatal acute ATLL emerging after methotrexate therapy for disseminated
      psoriasis.

PMID- 21729686
TI  - Addition of AEG35156 XIAP antisense oligonucleotide in reinduction chemotherapy
      does not improve remission rates in patients with primary refractory acute
      myeloid leukemia in a randomized phase II study.
AB  - BACKGROUND: XIAP (X-linked inhibitor of apoptosis protein) is an inhibitor of
      caspases 3 and 9 that is overexpressed in acute myeloid leukemia (AML) and may
      contribute to chemoresistance. We report an open-label randomized phase II trial
      of reinduction chemotherapy with and without the XIAP antisense oligonucleotide
      AEG35156 in patients with AML who did not achieve remission with initial
      induction chemotherapy. METHODS: Twenty-seven patients with AML who were
      refractory to initial induction chemotherapy were randomized and treated with
      AEG35156 (650 mg) in combination with high-dose cytarabine and idarubicin.
      Thirteen patients were randomized and treated with high-dose cytarabine and
      idarubicin alone. The rates of response and toxicity were determined. RESULTS: Of
      the 27 patients assigned to AEG35156 in combination with high-dose cytarabine and
      idarubicin, 3 died during reinduction chemotherapy, 5 achieved complete remission
      (CR), and 6 achieved CR with incomplete platelet count recovery (CRp), for an
      overall response rate of 41%. Of the 13 patients assigned to the control arm of
      the study, none died during reinduction, 6 achieved CR, and 3 achieved CRp, for
      an overall response rate of 69%. The differences in response rates between
      patients in the AEG35156 and control arms were not statistically different (P =
      0.18 by the chi(2) test). CONCLUSIONS: The addition of AEG35156 to reinduction
      chemotherapy was well tolerated but did not improve rates of remission. Therefore
      alternative therapeutic strategies should be explored in patients with AML
      refractory to induction chemotherapy.

PMID- 21729687
TI  - Paraneoplastic cutaneous leukocytoclastic vasculitis disclosing multiple myeloma:
      a case report.
AB  - Cutaneous lesions are unusual during the course of multiple myeloma. In rare
      cases, multiple myeloma may be associated to skin involvement secondary to
      amyloidosis, cryoglobulinemia, and POEMS syndrome. Paraneoplastic skin
      involvement occurs preferentially during solid neoplasms. We report the case of
      an uncommon presentation of an IgA lambda multiple myeloma in a 58 year-old woman
      preceded by vascular purpura with cutaneous leukocytoclastic vasculitis (LV) and
      intense deposit of IgA and kappa light chains in the dermal vessels. Purpura
      resolved after specific treatment of multiple myeloma and diagnosis of
      paraneoplastic purpura was asserted. We propose a brief review of the literature
      about skin involvement during multiple myeloma. This case highlights the
      necessity to search for MM when we are facing a LV.

PMID- 21729688
TI  - Prognostic significance of leukopenia at the time of diagnosis in acute myeloid
      leukemia.
AB  - We investigated the clinical significance of leukopenia at the time of diagnosis
      in a cohort of 225 patients with newly diagnosed acute myeloid leukemia (AML) at
      a single institution. Leukocyte count was treated as a continuous variable and,
      using a receiver operating characteristic curve (ROC), a cutoff of 3,600/MUL had
      the best sensitivity and specificity for remission (complete remission [CR]),
      relapse-free survival [RFS], and overall survival [OS]). In a multivariable
      model, leukopenia at diagnosis had no effects on CR (hazard ratio [HR] = 2.02;
      confidence interval [CI], 0.9-4.3; P = .07), RFS (HR = 0.93; CI, 0.5-1.5; P =
      .8), or OS (HR = 1.05; CI, 0.7-1.5; P = .7). No differential expression of cell
      surface molecules (CD34, c-Kit, CXCR4, PECAM, VLA2, VLA-, VLA4, VLA5, and FLT3)
      was observed on simultaneously obtained marrow and blood blasts in the high- vs.
      low-leukocyte groups. We conclude that leukopenia at diagnosis carries no
      prognostic significance in AML.

PMID- 21729689
TI  - A case of acute promyelocytic leukemia without RARalpha rearrangement and
      apparently normal cytogenetics.

PMID- 21729690
TI  - Hepatitis C reactivation in patients who have diffuse large B-cell lymphoma
      treated with rituximab: a case report and review of literature.
AB  - BACKGROUND: Whether to interrupt or to continue induction therapy for lymphoma
      when hepatitis C virus (HCV) reactivation occurs during therapy with rituximab
      and chemotherapy remains a controversial question. There is limited evidence
      based literature to help guide the management of patients with lymphoma in the
      setting of HCV reactivation. To address this issue we report an illustrative case
      and review the prevalence of non-Hodgkin lymphoma (NHL) in HCV-infected patients;
      the role of HCV in lymphomagenesis; the role of antiviral therapy in the
      management of HCV-associated lymphomas; as well as comparing the outcomes for NHL
      patients with and without HCV infection. CASE REPORT: A patient diagnosed with
      diffuse large B-cell lymphoma was treated with rituximab and chemotherapy with
      the patient achieving a complete remission, but treatment was complicated by
      asymptomatic HCV reactivation. Because conflicting data exist regarding
      management of such cases, the criteria for discontinuing chemotherapy, in the
      event of escalation in HCV replication in an asymptomatic patient, remain
      unclear. CONCLUSION: Patients with HCV have increased prevalence of marginal zone
      lymphoma, diffuse large B-cell lymphoma, and lymphoplasmacytic lymphoma. Whether
      HCV has a role in the lymphomagenesis is still uncertain, and limited to
      conjecture. The question whether to treat HCV-related lymphomas with antiviral
      therapy is debatable and not well-supported. Without initial liver dysfunction,
      HCV-infected patients can experience a similar outcome compared to their HCV
      negative counterparts when treated with standard chemotherapy/immunotherapy
      despite differences in the presentation of the disease.

PMID- 21729691
TI  - Chemoresistance as a function of the pretherapy tumor burden and the chemotherapy
      regimen administered: differences observed with 2 current chemotherapy regimens
      for advanced Hodgkin lymphoma.
AB  - BACKGROUND: The mature results from trials comparing ABVD (Adriamycin
      [doxorubicin], bleomycin, vinblastine, dacarbazine) and BEACOPP (bleomycin,
      etoposide, Adriamycin [doxorubicin], cyclophosphamide, Oncovin [vincristine],
      procarbazine, prednisone) chemotherapies in advanced Hodgkin lymphoma will be
      available in some years. An early comparison of their curative potential can
      however be obtained from an assessment of initial tumor burden and
      chemoresistance. PATIENTS AND METHODS: Less than a complete remission after
      treatment and relapse occurring within 12 months thereafter were assumed to be
      clinical expressions of chemoresistance. The tumor burden was calculated from the
      measurements of all the lesions documented by staging computed tomography (CT)
      and was normalized to body surface area to give the relative tumor burden (rTB).
      Using logistic regression analysis, the relationship between initial rTB,
      chemoresistance, and chemotherapy regimen administered was retrospectively
      studied in 222 patients selected from those enrolled in 2 similar randomized
      trials. RESULTS: The median rTB volumes were 157.9 cm(3)/m(2) in the 115 patients
      treated with ABVD vs. 154.6 cm(3)/m(2) in the 107 patients treated with BEACOPP,
      and the distribution of the volumes was identical in the 2 groups. The rTB was
      confirmed as the best predictor of early treatment failures (22 less than
      complete responses plus 21 early relapses). For the same rTB, the risk of
      chemoresistance to BEACOPP was about half that of the chemoresistance to ABVD or,
      for a given risk of chemoresistance, BEACOPP cured patients with an rTB 89.1
      cm(3)/m(2) greater than that cured by ABVD (ie, more than 50% of the median tumor
      load of patients with advanced-stage disease). CONCLUSION: This account of rTB
      allows an early comparative evaluation of the curative ability of different
      chemotherapy regimens.

PMID- 21729692
TI  - A limitation of the continuous spectrophotometric assay for the measurement of
      myo-inositol-1-phosphate synthase activity.
AB  - Myo-inositol-1-phosphate synthase (MIPS) catalyzes the conversion of glucose-6
      phosphate to myo-inositol-1-phosphate. The reaction catalyzed by MIPS is the
      first step in the biosynthesis of inositol and inositol-containing molecules that
      serve important roles in both eukaryotes and prokaryotes. Consequently, MIPS is a
      target for the development of therapeutic agents for the treatment of infectious
      diseases and bipolar disorder. We recently reported a continuous
      spectrophotometric method for measuring MIPS activity using a coupled assay that
      allows the rapid characterization of MIPS in a multiwell plate format. Here we
      validate the continuous assay as a high-throughput alternative for measuring MIPS
      activity and report on one limitation of this assay-the inability to examine the
      effect of divalent metal ions (at high concentrations) on MIPS activity. In
      addition, we demonstrate that the activity of MIPS from Arabidopsis thaliana is
      moderately enhanced by the addition Mg(2+) and is not enhanced by other divalent
      metal ions (Zn(2+) and Mn(2+)), consistent with what has been observed for other
      eukaryotic MIPS enzymes. Our findings suggest that the continuous assay is better
      suited for characterizing eukaryotic MIPS enzymes that require monovalent cations
      as cofactors than for characterizing bacterial or archeal MIPS enzymes that
      require divalent metal ions as cofactors.

PMID- 21729693
TI  - Anti-oxidant and anti-inflammatory mechanisms of amlodipine action to improve
      endothelial cell dysfunction induced by irreversibly glycated LDL.
AB  - Amlodipine, alone or in combination with other drugs, was successfully used to
      treat hypertension. Our aim was to evaluate the potential of amlodipine (Am) to
      restore endothelial dysfunction induced by irreversibly glycated low density
      lipoproteins (AGE-LDL), an in vitro model mimicking the diabetic condition. Human
      endothelial cells (HEC) from EA.hy926 line were incubated with AGE-LDL in the
      presence/absence of Am and the oxidative and inflammatory status of the cells was
      evaluated along with the p38 MAPK and NF-kappaB signalling pathways. The cellular
      NADPH activity, 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine levels in the
      culture medium and the adhesion of human monocytes to HEC were measured by
      chemiluminescence, UHPLC, Western Blot and spectrofluorimetric techniques. The
      gene expression of NADPH subunits (p22(phox), NOX4), eNOS and inflammatory
      molecules (MCP-1, VCAM-1) were determined by Real Time PCR, while the protein
      expression of p22(phox), MCP-1, iNOS, phospho-p38 MAPK and phospho-p65 NF-kappaB
      subunit were measured by Western Blot. Results showed that in HEC incubated with
      AGE-LDL, Am led to: (i) decrease of the oxidative stress: by reducing p22(phox),
      NOX4, iNOS expression, NADPH oxidase activity, 4-HNE and 3-nitrotyrosine levels;
      (ii) decrease of the inflammatory stress: by the reduction of MCP-1 and VCAM-1
      expression, as well as of the number of monocytes adhered to HEC; (iii)
      inhibition of ROS-sensitive signalling pathways: by decreasing phosphorylation of
      p38 MAPK and p65 NF-kappaB subunits. In conclusion, the reported data demonstrate
      that amlodipine may improve endothelial dysfunction in diabetes through anti
      oxidant and anti-inflammatory mechanisms.

PMID- 21729694
TI  - Biosensors in clinical chemistry - 2011 update.
AB  - Research activity and applications of biosensors for measurement of analytes of
      clinical interest over the last eight years are reviewed. Nanotechnology has been
      applied to improve performance of biosensors using electrochemical, optical,
      mechanical and physical modes of transduction, and to allow arrays of biosensors
      to be constructed for parallel sensing. Biosensors have been proposed for
      measurement of cancer biomarkers, cardiac biomarkers as well as biomarkers for
      autoimmune disease, infectious disease and for DNA analysis. Novel applications
      of biosensors include measurements in alternate sample types, such as saliva.
      Biosensors based on immobilized whole cells have found new applications, for
      example to detect the presence of cancer and to monitor the response of cancer
      cells to chemotherapeutic agents. The number of research reports describing new
      biosensors for analytes of clinical interest continues to increase; however,
      movement of biosensors from the research laboratory to the clinical laboratory
      has been slow. The greatest impact of biosensors will be felt at point-of-care
      testing locations without laboratory support. Integration of biosensors into
      reliable, easy-to-use and rugged instrumentation will be required to assure
      success of biosensor-based systems at the point-of-care.

PMID- 21729695
TI  - UVRAG is required for organ rotation by regulating Notch endocytosis in
      Drosophila.
AB  - Heterotaxy characterized by abnormal left-right body asymmetry causes diverse
      congenital anomalies. Organ rotation is a crucial developmental process to
      establish the left-right patterning during animal development. However, the
      molecular basis of how organ rotation is regulated is poorly understood. Here we
      report that Drosophila UV-resistance associated gene (UVRAG), a tumor suppressor
      that regulates autophagy and endocytosis, plays unexpected roles in controlling
      organ rotation. Loss-of-function mutants of UVRAG show seriously impaired organ
      rotation phenotypes, which are associated with defects in endocytic trafficking
      rather than autophagy. Blunted endocytic degradation by UVRAG deficiency causes
      endosomal accumulation of Notch, resulting in abnormally enhanced Notch activity.
      Knockdown of Notch itself or expression of a dominant negative form of Notch
      transcriptional co-activator Mastermind is sufficient to rescue the rotation
      defect in UVRAG mutants. Consistently, UVRAG-mutated heterotaxy patient cells
      also display highly increased Notch protein levels. These results suggest
      evolutionarily conserved roles of UVRAG in organ rotation by regulating Notch
      endocytic degradation.

PMID- 21729696
TI  - Elevated membrane attack complex in human choroid with high risk complement
      factor H genotypes.
AB  - Data from human genetics, histopathology, and animal models reveal a major role
      for the complement system in the development of age-related macular degeneration
      (AMD). Genetic variations in the complement factor H (CFH) gene are associated
      with an elevated risk of AMD. In this study we sought to determine whether eyes
      from donors with a high-risk genotype (homozygosity for the histidine allele at
      codon 402) exhibit altered levels of membrane attack complex (MAC) in the
      choroid, compared to eyes with a low risk genotype (homozygosity for tyrosine).
      Proteins were extracted from the RPE/choroid of 18 donors (10 low risk and 8 high
      risk) and levels of MAC were assessed using an ELISA assay. Eyes from donors
      homozygous for the histidine allele showed 69% higher levels of MAC than those
      homozygous for the tyrosine allele (p < 0.05), independent of whether the eyes
      showed signs of early AMD. Our results provide evidence that high-risk CFH
      genotypes may affect AMD risk by increased deposition of MAC around the aging
      choriocapillaris.

PMID- 21729697
TI  - A small cytoplasmic region adjacent to the fourth transmembrane segment of the
      alpha7 nicotinic receptor is essential for its biogenesis.
AB  - Deletion of a small cytoplasmic fragment close to the fourth transmembrane
      segment of the nicotinic alpha7 receptor (Glu437 to Arg447) abolished membrane
      expression. Different single mutants showed moderate to strong decreases in
      expression whereas the latter was totally abolished upon proline substitutions.
      We hypothesize that preservation of an alpha-helix formed by the fourth
      transmembrane segment and the adjacent cytoplasmic region is essential for
      membrane receptor expression. Moreover, in selected mutants with low or null
      membrane expression, a significant proportion of mature receptors was present
      inside the cell. Hence, elements in this cytoplasmic fragment might influence
      receptor transport to the membrane.

PMID- 21729698
TI  - Biosynthesis and secretion of mouse cysteine-rich with EGF-like domains 2.
AB  - In this study, we found that Cysteine-rich with EGF-like domains 2 (CRELD2), a
      novel endoplasmic reticulum stress-inducible protein, is not only localized in
      the ER-Golgi apparatus but also spontaneously secreted. Deletion of four C
      terminal amino acids from mouse CRELD2 or addition of tag-peptides to its C
      terminus dramatically enhanced CRELD2 secretion. Intra- and extra-cellular CRELD2
      is differentially glycosylated and its spontaneous secretion was significantly
      prevented by overexpression of a dominant negative mutant Sar1 and treatment with
      brefeldin A. Overexpression of wild-type GRP78 remarkably enhanced the secretion
      of wild-type but not mutant CRELD2. Our results demonstrate both that CRELD2 is a
      novel secretory glycoprotein regulated by Sar1 and GRP78 and that the C-terminal
      of CRELD2 plays a crucial role in its secretion.

PMID- 21729699
TI  - Vital functions of the malarial ookinete protein, CTRP, reside in the A domains.
AB  - The transformation of malaria ookinetes into oocysts occurs in the mosquito
      midgut and is a major bottleneck for parasite transmission. The secreted ookinete
      surface protein, circumsporozoite- and thrombospondin-related adhesive protein
      (TRAP)-related protein (CTRP), is essential for this transition and hence
      constitutes a potential target for malaria transmission blockade. CTRP is a
      modular multidomain protein containing six tandem von Willebrand factor A-like
      (A) domains and seven tandem thrombospondin type I repeat-like (TS) domains. Here
      we present, to our knowledge, the first structure-function analysis of CTRP using
      genetically modified Plasmodium berghei parasites expressing mutant versions of
      the ctrp gene. Our data show that the A domains of CTRP are critical for ookinete
      gliding motility and oocyst formation whilst, unexpectedly, its TS domains are
      fully redundant. These results may have important implications for the design of
      CTRP-based transmission blocking strategies.

PMID- 21729700
TI  - A simple competitive assay to determine peptide affinity for HLA class II
      molecules: a useful tool for epitope prediction.
AB  - We have designed a cytometry-based competition assay to evaluate peptide binding
      to empty recombinant HLA class II molecules. The efficiency of this assay was
      evaluated using recombinant HLA-DP0401 molecules (HLA-DP) produced in insect
      cells and 13 peptides from human telomerase reverse transcriptase (hTERT). We
      demonstrate that our method allowed accurate measurements of peptide Ki values
      and can thus discriminate strong, moderate and poor HLA-DP binders. In parallel,
      we showed that among hTERT peptides, the most immunodominant in healthy
      individuals were those with moderate affinity for HLA-DP while no T cell response
      could be evidenced against peptides with very strong or very low affinities for
      HLA-DP. This strongly suggests that the precise determination of peptide affinity
      with our method can improve HLA class II epitope prediction.

PMID- 21729701
TI  - Host plant volatiles induce oriented flight behaviour in male European grapevine
      moths, Lobesia botrana.
AB  - The European grapevine moth Lobesia botrana relies on a female produced sex
      pheromone for long-distance mate finding. Grapevine moth males compete heavily
      during limited time windows for females. The aim of this study was to investigate
      the perception of host plant volatiles by grapevine moth males and whether such
      compounds elicit upwind oriented flights. We compared five host plant headspace
      extracts by means of gas chromatography linked electroantennogram (EAG)
      recording. We identified 12 common host plant volatiles (aliphatic esters,
      aldehydes, and alcohols, aromatic compounds and terpenes) that elicit EAG
      responses from grapevine moth males and that occur in at least three of the host
      plant volatile headspace extracts tested. Subsequently the behavioural response
      of grapevine moth males to four these compounds presented singly and in mixtures
      (1-hexanol, 1-octen-3-ol, (Z)-3-hexenyl acetate and (E)-beta-caryophyllene) was
      recorded in a wind tunnel. Grapevine moth males engaged in upwind flights to all
      of four compounds when released singly at 10,000 pg/min and to all, except 1
      octen-3-ol, when released at 100 pg/min. A blend of the four host plant volatiles
      released at 10,000 pg/min and mixed at a ratio based on the analysis of Vitis
      vinifera cv. Solaris volatile emissions attracted significantly more males than
      any single compound. Grapevine moth males perceive and respond to host plant
      volatiles at biologically relevant levels indicating that host plant volatiles
      figure as olfactory cues and that L. botrana males can discern places where the
      likelihood of encountering females is higher.

PMID- 21729702
TI  - The inhibitory effect of the fungal toxin, destruxin A, on behavioural fever in
      the desert locust.
AB  - During an infection locusts behaviourally fever by seeking out higher
      environmental temperatures. This behaviour places the pathogen at sub-optimal
      growth temperatures while improving the efficiency of the immune system, thereby
      prolonging the lifespan of the host. It is therefore in the interest of the
      pathogen to either adapt to fever-like temperatures or to evolve mechanisms to
      interfere with, or inhibit fever. We investigated the behavioural fever response
      of desert locusts to two fungal pathogens. A prolonged fever was observed in
      locusts infected with Metarhizium acridum. However, fever was comparatively short
      lived during infection with Metarhizium robertsii. In both cases restriction of
      thermoregulation reduced lifespan. Destruxin A (dtx A) produced by M. robertsii,
      but not M. acridum has previously been associated with the inhibition of the
      insect immune system. Injection of dtx A during infection with the fever-causing
      M. acridum inhibited fever and was particularly effective when administered early
      on in infection. Furthermore, locusts injected with dtx A were more susceptible
      to M. acridum infection. Therefore engineering M. acridum isolates currently used
      for locust biocontrol, to express dtx A may improve efficiency of control by
      interfering with fever.

PMID- 21729703
TI  - Neuregulin-1beta for the treatment of systolic heart failure.
AB  - The Neuregulin-1 gene encodes a family of ligands that act through the ErbB
      family of receptor tyrosine kinases to regulate morphogenesis of many tissues.
      Work in isolated cardiac cells as well as genetically altered mice demonstrates
      that neuregulin-1/ErbB signaling is a paracrine signaling system that functions
      in endocardial-endothelial/cardiomyocyte interactions to regulate tissue
      organization during development as well as maintain cardiac function throughout
      life. Treatment of animals with cardiac dysfunction with recombinant neuregulin
      1beta improves cardiac function. This has led to ongoing early phase clinical
      studies examining neuregulin-1beta as a potential novel therapeutic for heart
      failure. In this review we synthesize the literature behind this rapidly evolving
      area of translational research. This article is part of a special issue entitled
      "Key Signaling Molecules in Hypertrophy and Heart Failure."

PMID- 21729704
TI  - Effects of allelochemicals produced by one population in a chemostat-like
      environment.
AB  - In this paper, we study some general models suggested to describe the effects of
      chemical compounds produced by an algal population on its survival in a chemostat
      like environment. The conditions for its persistence and extinction are found. In
      particular, in the first model we make very general assumptions to represent the
      uptake, the regulative and the inhibiting functions, and analyze its global
      stability completely. In the second one we specify the first two functions and
      leave general the third one. Here the regulative function has different property
      from that in the first model, and a saddle-node bifurcation phenomenon occurs. In
      addition, according to the experimental data reported in DellaGreca et al. [2010.
      Fatty acids released by Clorella vulgaris and their role in interference with
      Pseudokirchneriella subcapitata: experiments and modelling. J. Chem. Ecol. 36,
      339-349], we present a further model in which a new inhibiting function gives
      rise to a complex dynamics. The three models exhibit different dynamical
      behaviors, in particular the number of positive equilibria associated with each
      model varies resulting one, two and three, respectively. We also point out that
      the main differences exhibited by these models result from different
      specializations of the regulative and the inhibiting functions.

PMID- 21729705
TI  - Correlation between the flexibility and periodic dinucleotide patterns in yeast
      nucleosomal DNA sequences.
AB  - Nucleosome formation and positioning, which play important roles in a number of
      biological processes, are thought to be related to the distinctive periodic
      dinucleotide patterns observed in the DNA sequence wrapped around the protein
      octamer. Previous research shows that flexibility is a key structural property of
      a nucleosomal DNA sequence. However, the relationship between the flexibility and
      the periodic dinucleotide patterns has received little attention in research in
      the past. In this study, we propose the use of three different models to measure
      the flexibility of yeast DNA sequences. Although the three models involve
      different parameters, they deliver consistent results showing that yeast
      nucleosomal DNA sequences are more flexible than non-nucleosomal ones. In
      contrast to random flexibility values along non-nucleosomal DNA sequences, the
      flexibility of nucleosomal DNA sequences shows a clear periodicity of 10.14 base
      pairs, which is consistent with the periodicity of dinucleotide distributions. We
      also demonstrate that there is a strong relationship between the peak positions
      of the flexibility and the dinucleotide frequencies. Correlation between the
      flexibility and the dinucleotide patterns of CA/TG, CG, GC, GG/CC, AG/CT, AC/GT
      and GA/TC are positive with an average value of 0.5946. The highest correlation
      is shown by CA/TG with a value of 0.7438 and the lowest correlation is shown by
      AA/TT with a value of -0.7424. The source codes and data sets are available for
      downloading on http://www.hy8.com/bioinformatics.htm.

PMID- 21729706
TI  - Distinguishing graded and ultrasensitive signalling cascade kinetics by the shape
      of morphogen gradients in Drosophila.
AB  - Recently, signalling gradients in cascades of two-state reaction-diffusion
      systems were described as a model for understanding key biochemical mechanisms
      that underlie development and differentiation processes in the Drosophila embryo.
      Diffusion-trapping at the exterior of the cell membrane triggers the mitogen
      activated protein kinase (MAPK) cascade to relay an appropriate signal from the
      membrane to the inner part of the cytosol, whereupon another diffusion-trapping
      mechanism involving the nucleus reads out this signal to trigger appropriate
      changes in gene expression. Proposed mathematical models exhibit equilibrium
      distributions consistent with experimental measurements of key spatial gradients
      in these processes. A significant property of the formulation is that the signal
      is assumed to be relayed from one system to the next in a linear fashion.
      However, the MAPK cascade often exhibits nonlinear dose-response properties and
      the final remark of Berezhkovskii et al. (2009) is that this assumption remains
      an important property to be tested experimentally, perhaps via a new quantitative
      assay across multiple genetic backgrounds. In anticipation of the need to be able
      to sensibly interpret data from such experiments, here we provide a complementary
      analysis that recovers existing formulae as a special case but is also capable of
      handling nonlinear functional forms. Predictions of linear and nonlinear signal
      relays and, in particular, graded and ultrasensitive MAPK kinetics, are compared.

PMID- 21729707
TI  - Adaptive diversification of a plastic trait in a predictably fluctuating
      environment.
AB  - There is substantial evidence that evolutionary diversification can occur in
      allopatric conditions through reduction in the degree of phenotypic plasticity
      when an isolated population encounters a novel, more stable environment.
      Plasticity is no longer favored in the new environment, either because it carries
      an inherent physiological cost or because it leads to production of suboptimal
      phenotypes. In order to explore the role of phenotypic plasticity in sympatric
      diversification, we modeled the ecological and evolutionary dynamics of
      Escherichia coli bacteria in batch cultures. Our results describe an evolutionary
      pathway leading to metabolic diversification in a sympatric environment without
      spatial structure. In an environment that fluctuates widely and predictably,
      evolutionary branching leads to diversification and stable coexistence of
      generalist and specialist ecotypes for some combinations of parameters.
      Diversification and stable coexistence occur when reaction norms are steep and
      trade-offs between metabolic pathways are convex. We conclude that, in principle,
      diversification due to reduced plasticity can occur without allopatric isolation,
      reduced environmental variability, or an explicit cost of plasticity.

PMID- 21729708
TI  - Kin selection under blending inheritance.
AB  - Why did Darwin fail to develop his insights on kin selection into a proper theory
      of social adaptation? One suggestion has been that his inadequate understanding
      of heredity kept the problem out of focus. Here, I determine whether it is
      possible to develop a quantitative theory of kin selection upon the assumption of
      blending inheritance. I find that, whilst Hamilton's rule of kin selection can be
      readily derived under the assumption of blending inheritance, this mechanism
      complicates the computation of relatedness coefficients, and can even cause them
      to fluctuate over generations. Nevertheless, I show that the ultimate criterion
      for selection to favour any social trait - i.e. a time-average of Hamilton's rule
      - remains the same as under particulate inheritance. By eliminating the gene from
      the theory of kin selection, I clarify the role that it plays in the theory of
      social adaptation.

PMID- 21729709
TI  - With hands I do not centre! Action- and object-related effects of hand-cueing in
      the line bisection.
AB  - A variety of studies have shown action- and object-related visuo-motor priming in
      behavioural tasks. The peculiarity of this study lies in using a hand-cued line
      bisection task to explore the main properties of the motor effects evoked by
      action and object processing. In five experiments it is shown that flanking a
      line (thin vs. thick line) with images of hands (biological vs. non-biological
      hand) representing different actions (power vs. precision grip) biases
      performance towards the action more compatible with the object (power grip -
      thick line, precision grip - thin line). This effect is larger for the precision
      grip than for the power grip suggesting a functional rather than manipulative
      activation. In addition, the effect is larger for the biological than for the non
      biological hand. We suggest that this paradigm could be potentially useful for
      neuropsychological studies as well as for addressing unsolved issues of embodied
      theories of cognition.

PMID- 21729710
TI  - Relationship of androgens to body composition, energy and substrate metabolism
      and aerobic capacity in healthy, young women.
AB  - OBJECTIVE: To evaluate the role of physiologic levels of androgens and their
      precursors in the regulation of body composition, energy and substrate metabolism
      and aerobic capacity in healthy, cycling, premenopausal women. EXPERIMENTAL: We
      evaluated 30 young (27+/-1 year) premenopausal, non-obese (23+/-0.5 kg/m(2)),
      normally-cycling women, without clinical or chemical evidence of hyperandrogenism
      or hyperinsulinemia, for parameters of total and regional body composition,
      glucose tolerance, aerobic capacity and resting energy expenditure and substrate
      oxidation. Serum was assayed for androgens and androgen precursors by techniques
      optimized to assess the low androgen levels in this population. RESULTS: Higher
      serum testosterone levels correlated with greater fat mass (r=0.377; p=0.04), but
      not abdominal adiposity or other metabolic/physiologic variables. Additionally,
      dehydroepiandrosterone (DHEA) was negatively related to visceral fat content (r=
      0.569; p=0.02). Other serum androgens did not correlate with total or regional
      adiposity, skeletal muscle mass, aerobic capacity, glucose tolerance, or resting
      energy and substrate metabolism. CONCLUSION: In this group of non-obese,
      premenopausal women with no clinical or chemical evidence of hyperandrogenemia,
      serum testosterone levels were positively related with fat mass, but not with
      abdominal adiposity; whereas, DHEA was negatively related to visceral adiposity.
      Our data suggest that within the normal physiologic range, testosterone is a
      predictor of overall adiposity, but that this effect does not appear to be
      associated with concomitant alterations in resting energy or substrate metabolism
      that could predispose to weight gain.

PMID- 21729711
TI  - Synthesis of 3- and 21-monosulfates of [2,2,3beta,4,4-2H5]
      tetrahydrocorticosteroids in the 5beta-series as internal standards for mass
      spectrometry.
AB  - The 3- and 21-monosulfates of pentadeuterated 5beta-tetrahydrocorticosteroides
      were synthesized, starting from cortisol and 11-deoxycotisol. The principal
      reactions used were (1) perdeuteration of the methylene groups adjacent to the 3
      oxo group of 17,20:20,21-bismethylendioxy-5beta-3-ketosteroids with NaOD in
      CH(3)OD followed by stereoselective reduction with NaBD(4), (2) sulfation of
      hydroxy groups with sulfur trioxide-trimethylamine complex, and (3) removal of
      the 17,20:20,21-bismethylendioxy group with hydrogen fluoride. The labeled
      compounds can be used as internal standards in liquid chromatography/mass
      spectrometry assays for clinical and biochemical studies.

PMID- 21729712
TI  - Synthesis and biological evaluations of putative metabolically stable analogs of
      VN/124-1 (TOK-001): head to head anti-tumor efficacy evaluation of VN/124-1 (TOK
      001) and abiraterone in LAPC-4 human prostate cancer xenograft model.
AB  - In a continuing study of our clinical candidate 5 VN/124-1 (TOK-001) and analogs
      as potential agents for prostate cancer therapy, putative metabolites (10, 15 and
      18) of compound 5 were rationally designed and synthesized. However, none of
      these agents were as efficacious as 5 in several in vitro studies. Using western
      blot analysis, we have generated a preliminary structure-activity relationship
      (SAR) of 5 and related analogs as androgen receptor ablative agents (ARAAs). In
      vivo using the androgen-dependent LAPC-4 prostate cancer xenograft model, we
      demonstrated for the first time that 5 is more efficacious than the 17-lyase
      inhibitor 3 (abiraterone)/4 (abiraterone acetate) that is currently in phase III
      clinical trials. In our desire to optimize the potency of 5, compounds 6 (3xi
      fluoro-) and 9 (3beta-sulfamate-) designed to increase the stability and oral
      bioavailability of 5, respectively were evaluated in vivo. We showed, that on
      equimolar basis, compound 6 was ~2-fold more efficacious versus LAPC-4 xenografts
      than 5, but the toxicity observed with 6 is of concern. These studies further
      demonstrate the efficacy of 5 in a clinically relevant prostate cancer model and
      justify its current clinical development as a potential treatment of prostate
      cancer.

PMID- 21729713
TI  - Local metabolism of glucocorticoids in Prague hereditary hypertriglyceridemic
      rats--effect of hypertriglyceridemia and gender.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11HSD1) is a microsomal NADPH
      dependent oxidoreductase which elevates intracellular concentrations of active
      glucocorticoids. Data obtained from mouse strains with genetically manipulated
      11HSD1 showed that local metabolism of glucocorticoids plays an important role in
      the development of metabolic syndrome. Tissue specific dysregulation of 11HSD1
      was also found in other models of metabolic syndrome as well as in a number of
      clinical studies. Here, we studied local glucocorticoid action in the liver,
      subcutaneous adipose tissue (SAT) and skeletal muscles of male and female Prague
      hereditary hypertriglyceridemic rats (HHTg) and their normotriglyceridemic
      counterpart, the Wistar rats. 11HSD1 bioactivity was measured as a conversion of
      [(3)H]11-dehydrocorticosterone to [(3)H]corticosterone or vice versa.
      Additionally to express level of active 11HSD1 protein, enzyme activity was
      measured in tissue homogenates. mRNA abundance of 11HSD1, hexoso-6-phosphate
      dehydrogenase (H6PDH) and the glucocorticoid receptor (GR) was measured by real
      time PCR. In comparison with normotriglyceridemic animals, female HHTg rats
      showed enhanced regeneration of glucocorticoids in the liver and the absence of
      any changes in SAT and skeletal muscle. In contrast to females, the
      glucocorticoid regeneration in males of HHTg rats was unchanged in liver, but
      stimulated in SAT and downregulated in muscle. Furthermore, SAT and skeletal
      muscle exhibited not only 11-reductase but also 11-oxidase catalyzed by 11HSD1.
      In females of both strains, 11-oxidase activity largely exceeded 11-reductase
      activity. No dramatic changes were found in the mRNA expression of H6PDH and GR.
      Our data provide evidence that the relationship between hypertriglyceridemia and
      glucocorticoid action is complex and gender specific.

PMID- 21729714
TI  - New ester derivatives of dehydroepiandrosterone as 5alpha-reductase inhibitors.
AB  - The aim of this study was to synthesize different ester derivatives of
      dehydroepiandrosterone with therapeutic potential as antiandrogens. The
      biological effect of these steroids was demonstrated in in vivo as well as in
      vitro experiments. In the in vivo experiments, we measured the activity of seven
      steroids on the weight of the prostate and seminal vesicles of gonadectomized
      hamsters treated with testosterone. For the in vitro studies, we determined the
      IC(50) values by measuring the concentration of the steroidal derivatives that
      inhibits 50% of the activity of 5alpha-reductase present in human prostate and
      also its binding capacity to the androgen receptors (AR) obtained from rat's
      prostate cytosol. The results from these experiments indicated that compounds 7
      5alpha,6beta-dibromo-3beta-propanoyloxyandrostan-17-one, 8 5alpha,6beta-dibromo
      3beta-butanoyloxyandrostan-17-one and 9 5alpha,6beta-dibromo-3beta-(3'
      oxapentanoyloxy)-androstan-17-one, significantly decreased the weight of the
      prostate and seminal vesicles as compared to testosterone treated animals; this
      reduction of the weight of these glands was comparable to that produced by
      Finasteride 11. On the other hand, compounds 4 3beta-acetoxyandrost-5-en-17-one,
      5 3beta-hexanoyloxyandrost-5-en-17-one 6 3beta-(3'-oxapentanoyloxy)-androst-5-en
      17-one, 7 and 12 dehydroepiandrosterone, (commercially available) inhibited the
      enzyme 5alpha-reductase. Compounds 4, 5, 6, 8 and 9 (IC(50) values of 5.2+/-1.2,
      0.049+/-0.002, 6.4+/-1.1, 0.10+/-0.045, and 6.8+/-0.9 nM, respectively) exhibited
      the highest inhibitory activity. However, none of these compounds binds to the
      AR.

PMID- 21729715
TI  - The excitatory neurotransmitter glutamate stimulates DNA repair to increase
      neuronal resiliency.
AB  - Glutamate is the most abundant excitatory neurotransmitter in the vertebrate
      central nervous system and plays an important role in synaptic plasticity
      required for learning and memory. Activation of glutamate ionotropic receptors
      promptly triggers membrane depolarization and Ca(2+) influx, resulting in the
      activation of several different protein kinases and transcription factors. For
      example, glutamate-mediated Ca(2+) influx activates Ca(2+)/calmodulin-dependent
      kinase, protein kinase C, and mitogen activated protein kinases resulting in
      activation of transcription factors such as cyclic AMP response element binding
      protein (CREB). Abnormally prolonged exposure to glutamate causes neuronal
      injury, and such "excitotoxicity" has been implicated in many acute and chronic
      diseases including ischemic stroke, epilepsy, amyotrophic lateral sclerosis,
      Alzheimer's, Huntington's and Parkinson's diseases. Interestingly, although
      glutamate-induced Ca(2+) influx can cause DNA damage by a mitochondrial reactive
      oxygen species-mediated mechanism, the Ca(2+) simultaneously activates CREB,
      resulting in up-regulation of the DNA repair and redox protein
      apurinic/apyrimidinic endonuclease 1. Here, we review connections between
      physiological or aberrant glutamate receptor activation, Ca(2+)-mediated
      signaling, oxidative DNA damage and repair efficiency, and neuronal
      vulnerability. We conclude that glutamate signaling involves an adaptive cellular
      stress response pathway that enhances DNA repair capability, thereby protecting
      neurons against injury and disease.

PMID- 21729716
TI  - Integration of detailed modules in a core model of body fluid homeostasis and
      blood pressure regulation.
AB  - This paper presents a contribution to the definition of the interfaces required
      to perform heterogeneous model integration in the context of integrative
      physiology. A formalization of the model integration problem is proposed and a
      coupling method is presented. The extension of the classic Guyton model, a multi
      organ, integrated systems model of blood pressure regulation, is used as an
      example of the application of the proposed method. To this end, the Guyton model
      has been restructured, extensive sensitivity analyses have been performed, and
      appropriate transformations have been applied to replace a subset of its
      constituting modules by integrating a pulsatile heart and an updated
      representation of the renin-angiotensin system. Simulation results of the
      extended integrated model are presented and the impacts of their integration
      within the original model are evaluated.

PMID- 21729717
TI  - Stress and consumption of alcohol in humans with a Type 1 family history of
      alcoholism in an experimental laboratory setting.
AB  - BACKGROUND: This paper investigates how stress interacts with alcohol consumption
      in subjects with a family history of alcoholism. One mechanism for increases in
      alcohol intake may be that stress alters the subjective effects produced by the
      drug. METHODS: 58 healthy volunteers, divided into two groups of family history
      positive (FHP) and two groups of family history negative (FHN) participated in
      two laboratory sessions, in which they performed in one out of two sessions a
      stress task. Then subjects were allowed to choose up to six additional drinks of
      ethanol or placebo depending on which session they were randomly assigned to
      start with. RESULTS: It was found that FHP subjects increased their consumption
      of alcohol after stress. CONCLUSIONS: It is possible that both stress and alcohol
      specifically exaggerate the feelings of the reward in the FHP individuals in such
      way that it may increase the likelihood of consuming more alcohol.

PMID- 21729718
TI  - Interaction of lysozyme with gold nanorods: conformation and activity
      investigations.
AB  - Gold nanorods, with their unique morphology and optical properties have offered
      new prospects for biomedical and biosensing applications. Herein, the interaction
      between gold nanorods and a model protein has been monitored using spectroscopic
      techniques. The enzyme retains high fraction of its native structure with a
      slight increase in the helical content at the expense of beta-turns. Kinetic
      investigations revealed notable increase of enzyme affinity for substrate without
      significant decrease in the V(max). Emission spectra of tryptophan residues in
      the presence of chaotropic agent highlighted the maintenance of internal
      quenching due to the induced compactness. Comparison of the gold nanorod treated
      lysozyme with free enzyme revealed higher thermodynamic stability under
      denaturing condition. Results from this study encourage the possibility of
      utilizing gold nanorods as promising nanocarrier candidates for a new generation
      of drug delivery applications.

PMID- 21729719
TI  - Electrochemical and spectroscopic study on the interaction between isoprenaline
      and DNA using multivariate curve resolution-alternating least squares.
AB  - Interaction of isoprenaline (ISO) with calf-thymus DNA was studied by
      spectroscopic and electrochemical methods. The behavior of ISO was investigated
      at a glassy carbon electrode (GCE) by cyclic voltammetry (CV) and differential
      pulse stripping voltammetry (DPSV); ISO was oxidized and an irreversible
      oxidation peak was observed. The binding constant K and the stoichiometric
      coefficient m of ISO with DNA were evaluated. Also, with the addition of DNA,
      hyperchromicity of the UV-vis absorption spectra of ISO was noted, while the
      fluorescence intensity decreased significantly. Multivariate curve resolution
      alternating least squares (MCR-ALS) chemometrics method was applied to resolve
      the combined spectroscopic data matrix, which was obtained by the UV-vis and
      fluorescence methods. Pure spectra of ISO, DNA and ISO-DNA complex, and their
      concentration profiles were then successfully obtained. The results indicated
      that the ISO molecule intercalated into the base-pairs of DNA, and the complex of
      ISO-DNA was formed.

PMID- 21729720
TI  - Modulation of human GABAA receptor function: a novel mode of action of drugs of
      abuse.
AB  - Drugs of abuse are known to mainly affect the dopaminergic and serotonergic
      system, although behavioral studies indicated that the GABA-ergic system also
      plays a role. We therefore investigated the acute effects of several commonly
      used drugs of abuse (methamphetamine, amphetamine, 3,4
      methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and
      meta-chlorophenylpiperazine (mCPP)) on the function of the human
      alpha(1)beta(2)gamma(2) GABA(A) receptor (hGABA(A)-R), expressed in Xenopus
      oocytes, using the two-electrode voltage-clamp technique. Although none of the
      tested drugs acted as full agonist on the hGABA(A)-R, some drugs induced
      differential modulation of hGABA(A)-R function, depending on the degree of
      receptor occupancy. Methamphetamine did not affect the GABA-evoked current at
      high receptor occupancy, but induced a minor inhibition at low receptor
      occupancy. Its metabolite amphetamine slightly potentiated the GABA-evoked
      current. MDMA and its metabolite MDA both inhibited the current at low receptor
      occupancy. However, MDMA did not affect the current at high occupancy, whereas
      MDA induced a potentiation. mCPP induced a strong inhibition (max. ~ 80%) at low
      receptor occupancy, but ~ 25% potentiation at high receptor occupancy.
      Competitive binding to one of the GABA-binding sites could explain the drug
      induced inhibitions observed at low receptor occupancy, whereas an additional
      interaction with a positive allosteric binding site may play a role in the
      observed potentiations at high receptor occupancy. This is the first study to
      identify direct modulation of hGABA(A)-Rs as a novel mode of action for several
      drugs of abuse. Consequently, hGABA(A)-Rs should be considered as target for
      psychiatric pharmaceuticals and in developing treatment for drug intoxications.

PMID- 21729721
TI  - Diversity of the inferior frontal gyrus--a meta-analysis of neuroimaging studies.
AB  - PURPOSE: The inferior frontal gyrus (IFG) has attracted a lot of interest due to
      its involvement in motor control and language processing. More recently, it has
      also been implicated for the processing of empathy. The aim of this meta-analysis
      was to investigate if neuroimaging studies in humans reveal distinct foci related
      to empathy as compared to those in motor and speech control in the IFG. MATERIALS
      AND METHODS: We reviewed MEDLINE for functional imaging studies on healthy
      subjects published between 1991 and 2007. With the search terms "inferior frontal
      gyrus", and "statistical parametric mapping" 485 studies were identified. We
      performed a non-hierarchical cluster-centre analysis of the stereotactic
      coordinates of the reported 1042 significant activation peaks and investigated
      seven functional categories using a score of specificity (SCSP). RESULTS: We
      found four significant, spatially distinct clusters. Three left-hemispheric
      clusters included one for processing of empathy, one closely adjacent for
      semantic and phonological processing, and one for working memory, while one
      cluster for fine movement control was located in the right hemisphere.
      CONCLUSIONS: This meta-analysis demonstrates a spatio-functional diversity of the
      left human IFG for processing of language, working memory and empathy. Notably,
      phonological and semantic processing collapsed into one cluster. Fine movement
      control located in a cluster in the right IFG occurred in a virtually mirror-like
      location to processing of empathy in the left hemisphere. These observations are
      in accordance with the notion of the mirror neuron system mediating specialized
      links between perception and action.

PMID- 21729722
TI  - Neurochemical and electrophysiological changes induced by paradoxical sleep
      deprivation in rats.
AB  - The present study aims to investigate the effects of paradoxical sleep
      deprivation (PSD) on the waking EEG and amino acid neurotransmitters in the
      hippocampus and cortex of rats. Animals were deprived of paradoxical sleep for
      72h by using the multiple platform method. The EEG power spectral analysis was
      carried out to assess the brain's electrophysiological changes due to sleep
      deprivation. The concentrations of amino acid neurotransmitters were assessed in
      the hippocampus and cortex using HPLC. Control data showed slight differences
      from normal animals in the delta, theta and alpha waves while an increase in the
      beta wave was obtained. After 24h of PSD, delta relative power increased and the
      rest of EEG wave's power decreased with respect to control. After 48h and 72h the
      spectral power analysis showed non-significant changes to control. The amino acid
      neurotransmitter analysis revealed a significant increase in cortical glutamate,
      glycine and taurine levels while in the hippocampus, glutamate, aspartate,
      glutamine and glycine levels increased significantly. Both the waking EEG and
      neurotransmitter analyses suggest that PSD induced neurochemical and
      electrophysiological changes that may affect brain proper functionality.

PMID- 21729723
TI  - Gender differences and the relationships of perceived background stress and
      psychological distress with cardiovascular responses to laboratory stressors.
AB  - The primary aim of this study was to evaluate the relationships of perceived
      background stress and self-reported psychological distress on cardiovascular
      reactivity during acute laboratory stressors. The Perceived Stress Scale (PSS)
      was used as the measure of perceived background stress, and the General Health
      Questionnaire (GHQ) was used as the measure of psychological distress. A
      secondary aim was to examine whether background stress and psychological distress
      affected the susceptibility to induction of a negative mood using music. Heart
      rate (HR) and blood pressure (BP) were measured in 149 female and male college
      students at rest and during a stressful mental arithmetic (MA) task and a mood
      induction procedure. Higher scores on the GHQ were associated with lower systolic
      BP reactivity during the MA task by all participants. Higher scores on the PSS
      and GHQ were also associated with lower diastolic BP and HR reactivity, but only
      in females. Thus, higher self-reports of background stress and psychological
      distress tended to result in blunted reactivity to an acute laboratory challenge.
      Higher levels of background stress and psychological distress were not associated
      with greater susceptibility to a negative mood induction. This study adds to the
      growing literature indicating that potentially negative health outcomes may be
      associated with diminished cardiovascular reactivity under certain conditions.

PMID- 21729724
TI  - Lactic acid production from lignocellulose-derived sugars using lactic acid
      bacteria: overview and limits.
AB  - Lactic acid is an industrially important product with a large and rapidly
      expanding market due to its attractive and valuable multi-function properties.
      The economics of lactic acid production by fermentation is dependent on many
      factors, of which the cost of the raw materials is very significant. It is very
      expensive when sugars, e.g., glucose, sucrose, starch, etc., are used as the
      feedstock for lactic acid production. Therefore, lignocellulosic biomass is a
      promising feedstock for lactic acid production considering its great
      availability, sustainability, and low cost compared to refined sugars. Despite
      these advantages, the commercial use of lignocellulose for lactic acid production
      is still problematic. This review describes the "conventional" processes for
      producing lactic acid from lignocellulosic materials with lactic acid bacteria.
      These processes include: pretreatment of the biomass, enzyme hydrolysis to obtain
      fermentable sugars, fermentation technologies, and separation and purification of
      lactic acid. In addition, the difficulties associated with using this biomass for
      lactic acid production are especially introduced and several key properties that
      should be targeted for low-cost and advanced fermentation processes are pointed
      out. We also discuss the metabolism of lignocellulose-derived sugars by lactic
      acid bacteria.

PMID- 21729725
TI  - Heat shock protein 40 (Hsp40) plays a key role in the virus life cycle.
AB  - The heat shock proteins (Hsps) are a diverse subset of molecular chaperones that
      generally promote the proper folding of proteins after translation and also
      prevent their aggregation during cellular stress. Paradoxically, cellular
      chaperones might perform important antiviral functions for host cells, yet, at
      the same time, might be beneficial for virus replication. Among them, Hsp40 is a
      specialized co-chaperone that has recently received much attention for its
      crucial role in both constitutive cellular functions and virus pathogenicity. The
      aim of this review is to raise awareness of its importance in the life cycles of
      a wide range of viruses.

PMID- 21729726
TI  - Quantum dots to tail single bio-molecules inside living cells.
AB  - In the last two decades, the single particle and single molecule approach became
      more and more popular to investigate the activity and the mechano-chemical
      properties of biological molecules. The inherent limit of these assays was that
      the molecules of interest were observed in vitro, out of their natural
      environment, the cell. Several recent works have shown the possibility to
      overcome this limit, to extend this approach to living cells and to observe the
      details of many cellular processes at the molecular level. In this review we
      discuss the use of semiconductor quantum dots to perform single particle and
      single molecule tracking in the cell. We refer to other articles for the
      technical aspects of this method. Here, after an introduction on the advantages
      provided by these nanoparticles, we restrict ourselves to some examples, mainly
      related to intracellular transport and molecular motor activity. These will
      illustrate the important role played by semiconductor quantum dots as fluorescent
      nano-reporters in in cell single molecule approach in modern biology and
      biophysics.

PMID- 21729727
TI  - Oxide and hybrid nanostructures for therapeutic applications.
AB  - The research on biomedical applications of nanoparticles has seen an upsurge in
      recent years due to their unique capabilities in treatment of ailments. Though
      there are ample reviews on the advances of nanoparticles right from their
      fabrication to applications, comparatively fewer reviews are available for the
      nanostructured materials particularly on oxides and hybrids. These materials
      possess unique physicochemical properties with an ability to get functionalized
      at molecular and cellular level for biochemical interactions. Keeping the
      enormosity of the nanostructures in mind, we intend to cover only the recent and
      most noteworthy developments in this area. We, particularly emphasize on iron
      oxide and its derivatives, zinc oxides, layered double hydroxides, silica and
      binary/ternary metal oxides and their applications in the area of therapeutics.
      This review also focuses on the designing of biodegradable and biocompatible
      nanocarriers and critical issues related to their therapeutic applications.
      Several representative examples discuss targeting strategies and stimuli
      responsive nanocarriers and their therapeutics.

PMID- 21729728
TI  - A qualitative difference. Patients' views of hospital food service in Iran.
AB  - Undernutrition and food acceptability in hospitals form a worldwide problem, but
      existing studies offer a predominantly Western perspective. This research
      investigated inpatients' satisfaction with meals in five Iranian hospitals, using
      focus group discussions, interviews and meal observations. The main problem areas
      included food quality and quantity, nutritional control, meal arrangements and
      staff attitudes. Iran's hospitals follow a Western model, which may be
      appropriate for medical systems, but is less so for patient feeding, due to
      budgetary constraints and cultural factors. Understanding patients' experience
      makes it possible to improve feeding arrangements, with a positive impact upon
      patients' nutrition.

PMID- 21729730
TI  - On the local cardiac renin angiotensin system. Basic and clinical implications.
AB  - In the present review we reevaluated the experimental and clinical evidence that
      there is a local renin angiotensin system in the heart as well as the presence of
      a functional intracrine component which is activated during pathological
      conditions like heart failure and hypertension. The implications of these
      findings for cardiology were discussed. The novel finding that cell swelling
      impairs cell coupling and impulse propagation through activation of ionic
      channels with consequent generation of cardiac arrhythmias and the evidence that
      AT1 receptors are mechanosensors able to alter the heart function independently
      of Ang II were discussed. Particular attention was given to the role of salt
      loading on the activation of a local cardiac renin angiotensin and its
      consequences.

PMID- 21729729
TI  - Pharmacology and selectivity of various natural and synthetic bombesin related
      peptide agonists for human and rat bombesin receptors differs.
AB  - The mammalian bombesin (Bn)-receptor family [gastrin-releasing peptide-receptor
      (GRPR-receptor), neuromedin B-receptor (NMB receptor)], their natural ligands,
      GRP/NMB, as well as the related orphan receptor, BRS-3, are widely distributed,
      and frequently overexpressed by tumors. There is increased interest in agonists
      for this receptor family to explore their roles in
      physiological/pathophysiological processes, and for receptor-imaging/cytotoxicity
      in tumors. However, there is minimal data on human pharmacology of Bn receptor
      agonists and most results are based on nonhuman receptor studies, particular
      rodent-receptors, which with other receptors frequently differ from human
      receptors. To address this issue we compared hNMB-/GRP-receptor affinities and
      potencies/efficacies of cell activation (assessing phospholipase C activity) for
      24 putative Bn-agonists (12 natural, 12 synthetic) in four different cells with
      these receptors, containing native receptors or receptors expressed at
      physiological densities, and compared the results to native rat GRP-receptor
      containing cells (AR42J-cells) or rat NMB receptor cells (C6-glioblastoma cells).
      There were close correlations (r=0.92-99, p<0.0001) between their
      affinities/potencies for the two hGRP- or hNMB-receptor cells. Twelve analogs had
      high affinities (<= 1 nM) for hGRP receptor with 15 selective for it
      (greatest=GRP, NMC), eight had high affinity/potencies for hNMB receptors and
      four were selective for it. Only synthetic Bn analogs containing beta-alanine(11)
      had high affinity for hBRS-3, but also had high affinities/potencies for all GRP
      /hNMB-receptor cells. There was no correlation between affinities for human GRP
      receptors and rat GRP receptors (r=0.131, p=0.54), but hNMB receptor results
      correlated with rat NMB receptor (r=0.71, p<0.0001). These results elucidate the
      human and rat GRP-receptor pharmacophore for agonists differs markedly, whereas
      they do not for NMB receptors, therefore potential GRP-receptor agonists for
      human studies (such as Bn receptor-imaging/cytotoxicity) must be assessed on
      human Bn receptors. The current study provides affinities/potencies on a large
      number of potential agonists that might be useful for human studies.

PMID- 21729731
TI  - WHO Working Group discussion on revision of the WHO recommendations for the
      production and control of poliomyelitis vaccines (oral): TRS Nos. 904 and 910.
      Report of Meeting held on 20-22 July 2010, Geneva, Switzerland.
AB  - Oral poliomyelitis vaccine (OPV) is a critical part of the polio eradication
      programme. A high number of doses are administered each year with an impact on
      billions of citizens worldwide. It is therefore essential that written standards
      concerning OPV are up to date and widely available. The World Health Organization
      (WHO) publishes technical guidance on the quality, safety and efficacy of
      vaccines intended to assist national regulatory authorities (NRAs), national
      control laboratories (NCLs) and manufacturers. As part of its programme, on 20-22
      July 2010 WHO convened a working group meeting to initiate the revision of the
      WHO recommendations on the production and control of OPV as presently outlined in
      the Technical Reports Series (TRS) issues Nos. 904 and 910 [1,2]. The attendees
      included experts from academia, NRAs/NCLs and industry involved in the study,
      manufacture, and authorization and testing/release of OPV from countries around
      the world including representatives from China, the European Union, Indonesia,
      Japan, Mexico, and the USA. The objective was to review the state of knowledge
      concerning production and control of OPV, with a focus on neurovirulence testing,
      to determine how the existing guidelines should be updated and what
      recommendations should be made for the future. The outcomes of this meeting will
      be taken into consideration in future revision of the WHO TRS.

PMID- 21729732
TI  - The immunogenicity and safety of pneumococcal conjugate vaccine in human
      immunodeficiency virus-infected Thai children.
AB  - BACKGROUND: HIV-infected children have high risk of invasive pneumococcal disease
      (IPD) despite receiving highly active antiretroviral therapy (HAART). This study
      aimed to determine the immunogenicity and safety of a 7-valent pneumococcal
      conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed
      uninfected children. METHODS: A prospective study was conducted among children 2
      months to 9 years. The number of PCV-7 doses depended upon age and HIV status; 2
      6 months of age: 3 doses; 7-23 months of age: 2 doses; HIV-infected child >=24
      months: 2 doses and HIV-exposed child >=24 months: 1 dose. Serotype-specific
      pneumococcal IgG antibody concentrations were measured at baseline and 28 days
      after complete vaccination. The primary end point was the proportion of children
      who achieved serotype-specific IgG antibody concentration at a cut off level
      >=0.35 MUg/mL. Secondary end points were a 4-fold increase in serotype-specific
      IgG antibody, rates of adverse events and predictors for seroconversion among HIV
      infected children. RESULTS: Fifty-nine HIV-infected and 30 HIV-exposed children
      were enrolled. The median (IQR) age was 97 (67-111) and 61 months (51-73),
      respectively (p<0.001). Among HIV-infected children, current and nadir CD4 counts
      were 1,079 cell/mm(3) and 461 cell/mm(3), respectively. The proportion of
      children who achieved pneumococcal IgG >=0.35 MUg/mL was in the range of 85-98%
      in HIV-infected and 83-100% in HIV-exposed children depending on serotype. The
      lowest response was to serotype 6B in both groups. The 4-fold increase in
      serotype-specific IgG concentrations was similar between HIV-infected and HIV
      exposed groups, except for serotype 9V (p=0.027). HIV-infected children who had a
      history of AIDS had a lower antibody response to serotype 23F (p=0.025). Seven
      (12%) HIV-infected children had a grade 3 local reaction. CONCLUSION: PCV-7 is
      highly immunogenic and safe among HIV-infected children treated with HAART. The
      use of the pneumococcal conjugate vaccine among HIV-infected children is
      encouraged in order to prevent IPD.

PMID- 21729733
TI  - Acute and 90-day subchronic toxicity studies of Silk peptide E5K6, in Sprague
      Dawley rats.
AB  - Acute and 90-day subchronic oral toxicity studies of Silk peptide E5K6 were
      performed in Sprague-Dawley rats. In the acute toxicity study, Silk peptide E5K6
      was administered orally to male and female rats at a single dose of 2000 and 5000
      mg/kg. Mortality, clinical signs and body weight changes were monitored for 14
      days. There were no treatment-related changes in these parameters. Therefore, the
      Approximate Lethal Dose (ALD) of Silk peptide E5K6 in male and female rats is
      higher than 5000 mg/kg. In the subchronic toxicity study, Silk peptide E5K6 was
      administered orally to male and female rats for 90 days at a single dose of 500,
      1000, and 2000 mg/kg. There were no toxicologically significant changes in
      clinical signs, body weight, food and water consumptions, ophthalmoscopic
      examination, urinalysis, hematological and serum biochemical examinations,
      necropsy findings, organ weights and histopathological examination of all of the
      animals treated with Silk peptide E5K6. These results suggest that the oral No
      Observed Adverse-Effect Level (NOAEL) of Silk peptide E5K6 is greater than 2000
      mg/kg/day in both sexes and the target organs were not established.

PMID- 21729734
TI  - Molecular characterization of a novel thermostable mannose-6-phosphate isomerase
      from Thermus thermophilus.
AB  - Mannose-6-phosphate isomerase catalyzes the interconversion of mannose-6
      phosphate and fructose-6-phosphate. The gene encoding a putative mannose-6
      phosphate isomerase from Thermus thermophilus was cloned and expressed in
      Escherichia coli. The native enzyme was a 29 kDa monomer with activity maxima for
      mannose 6-phosphate at pH 7.0 and 80  degrees C in the presence of 0.5 mM Zn(2+)
      that was present at one molecule per monomer. The half-lives of the enzyme at 65,
      70, 75, 80, and 85  degrees C were 13, 6.5, 3.7, 1.8, and 0.2 h, respectively.
      The 15 putative active-site residues within 4.5 A of the substrate mannose 6
      phosphate in the homology model were individually replaced with other amino
      acids. The sequence alignments, activities, and kinetic analyses of the wild-type
      and mutant enzymes with amino acid changes at His50, Glu67, His122, and Glu132 as
      well as homology modeling suggested that these four residues are metal-binding
      residues and may be indirectly involved in catalysis. In the model, Arg11, Lys37,
      Gln48, Lys65 and Arg142 were located within 3 A of the bound mannose 6-phosphate.
      Alanine substitutions of Gln48 as well as Arg142 resulted in increase of K(m) and
      dramatic decrease of k(cat), and alanine substitutions of Arg11, Lys37, and Lys65
      affected enzyme activity. These results suggest that these 5 residues are
      substrate-binding residues. Although Trp13 was located more than 3 A from the
      substrate and may not interact directly with substrate or metal, the ring of
      Trp13 was essential for enzyme activity.

PMID- 21729735
TI  - Coding vs non-coding: Translatability of short ORFs found in putative non-coding
      transcripts.
AB  - Genome analysis has identified a number of putative non-protein-coding
      transcripts that do not contain ORFs longer than 100 codons. Although evidence
      strongly suggests that non-coding RNAs are important in a variety of biological
      phenomena, the discovery of small peptide-coding mRNAs confirms that some
      transcripts that have been assumed to be non-coding actually have coding
      potential. Their abundance and importance in biological phenomena makes the
      sorting of non-coding RNAs from small peptide-coding mRNAs a key issue in
      functional genomics. However, validating the coding potential of small peptide
      coding RNAs is complicated, because their ORF sequences are usually too short for
      computational analysis. In this review, we discuss computational and experimental
      methods for validating the translatability of these non-coding RNAs.

PMID- 21729736
TI  - Identification of potentially new bifunctional RNA based on genome-wide data
      mining of alternative splicing events.
AB  - It is now evident that the transcriptional output of the genome is much more
      complex than estimates based on the number of protein-coding genes, and that non
      coding RNA widely increase the source of regulatory molecules, a role previously
      ascribed to proteins. Furthermore, the recent characterization of bifunctional
      RNA, i.e. RNA for which both coding capacity and activity as functional RNA have
      been reported, adds an additional degree of complexity. Based on the SRA (Steroid
      Receptor RNA Activator) model, where bifunctionality is regulated by alternative
      splicing, we hypothesized that similar cases, not yet formally tested
      experimentally, might exist. Using freely available data from high-throughput
      sequencing projects, we propose here a bioinformatical identification of mRNA
      whose ORF are disrupted by alternative splicing events, especially by intron
      retention, and potentially representing a cognate non-coding RNA. Our data-mining
      approach revealed that the human genome contains around 300 possibilities of
      potentially new bifunctional RNA.

PMID- 21729737
TI  - Robustness of circadian rhythms in the presence of molecular fluctuations: an
      investigation based on a mechanistic, statistical theory and a simulation
      algorithm.
AB  - After a very brief introduction to a mechanistic and statistical theory of
      molecular fluctuations in chemical reactions developed by Joel Keizer, we explore
      the robustness of a circadian rhythm model by using the theory and the exact
      stochastic simulation (ESS). The comparative study shows that the theory reflects
      the effects of the dynamics of the model on the robustness more than ESS does.
      Even though the theory is a macroscopic one, the robustness of the model compares
      well with that computed from the ESS when the system size is larger than 50. The
      robustness increases nonlinearly with the system size and it reaches an
      asymptotic value at higher system sizes. As we can expect from the dynamics of
      the system, the robustness is minimum near the bifurcation point and as the most
      sensitive parameter increases away from the bifurcation point the robustness
      according to the theory as well as the ESS increases and then reaches to a steady
      value.

PMID- 21729738
TI  - A DNA assembly model of sentence generation.
AB  - Recent results of corpus-based linguistics demonstrate that context-appropriate
      sentences can be generated by a stochastic constraint satisfaction process.
      Exploiting the similarity of constraint satisfaction and DNA self-assembly, we
      explore a DNA assembly model of sentence generation. The words and phrases in a
      language corpus are encoded as DNA molecules to build a language model of the
      corpus. Given a seed word, the new sentences are constructed by a parallel DNA
      assembly process based on the probability distribution of the word and phrase
      molecules. Here, we present our DNA code word design and report on successful
      demonstration of their feasibility in wet DNA experiments of a small scale.

PMID- 21729739
TI  - Uncoupling protein 2 knockout exacerbates depression-like behaviors in mice via
      enhancing inflammatory response.
AB  - Mitochondrial uncoupling protein 2 (UCP2) has been recognized as an important
      protein to regulate reactive oxygen species (ROS) production. The absence of UCP2
      has the potential to promote ROS accumulation and thereby induces oxidative
      damages and inflammatory response. Increasing evidence strongly reveals that
      depression is accompanied by oxidative stress, so the present study was to
      investigate the impacts of UCP2 on the etiology of depression. Wild-type and UCP2
      knockout mice were used to establish chronic mild stress (CMS)-induced anhedonia
      model of depression. The results showed that CMS led to more severe depressive
      responses in UCP2 knockout mice, characterized by exacerbated depression-like
      behaviors, increased corticosterone level and significant loss of weight.
      Moreover, CMS resulted in a higher mortality in UCP2 knockout mice. Our further
      study showed that UCP2 knockout enhanced CMS-induced activation of nuclear factor
      kappaB (NF-kappaB) p65 and increased mRNA expression of tumor necrosis factor
      alpha (TNF-alpha) in hypothalamus. And the levels of TNF-alpha of serum and
      spleen in UCP2 knockout mice are remarkably enhanced by CMS, even under basal
      conditions. Therefore, our findings suggest that UCP2 knockout-induced
      inflammation may contribute to the development of depressive symptoms.

PMID- 21729740
TI  - Nuclear factor-kappa beta regulates Notch signaling in production of
      proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells.
AB  - Microglial cells exhibit Notch-1 signaling expression which is enhanced upon
      activation. We reported previously that enhanced Notch-1 expression in activated
      microglia modulates production of proinflammatory cytokines and nitric oxide
      (NO). Furthermore, Notch-1 modulates transcription factor nuclear factor-kappa B
      (NF-kappaB). This study was aimed to investigate if NF-kappaB reciprocally
      modulates Notch signaling in BV-2 cells. In this connection, the cells were
      pretreated with caffeic acid phenethyl ester (Cape) followed by stimulating the
      cells with lipopolysaccharide (LPS). Cape+LPS treatment resulted in reduced
      translocation of NF-kappaB into the nucleus. Concomitantly, NF-kappaB DNA binding
      activity and the mRNA and protein expression levels of NF-kappaB/p65, Notch-1,
      intracellular domain of Notch-1 receptor (NICD), Hes-1, tumor necrosis factor
      alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and inducible nitric oxide
      synthase (iNOS) along with nitrite level were significantly reduced.
      Additionally, flow cytometry analysis showed a decrease in expression levels of
      NF-kappaB/p65, Notch-1, NICD but an increase in that of signal transducers and
      activators of transcription 3 (Stat3). Furthermore, nuclear Hes-1, phosphorylated
      Stat3 (p-Stat3) and recombination signal-binding protein 1 for J-Kappa (RBP-JK)
      expression levels were significantly suppressed. The present results suggest that
      Cape inhibits NF-kappaB activation through suppressing its interaction with DNA.
      Cape-induced reduction of Hes-1 may be attributed to decreased interaction
      between NICD and RBP-JK whose levels were reduced concurrently. Hes-1 reduction
      may lead to decreased production of inflammatory cytokines and NO. It is
      concluded that NF-kappaB can modulate Notch-1 signaling. Both pathways operate
      synergistically for production of proinflammatory cytokines and NO in activated
      microglia.

PMID- 21729741
TI  - Transport of animals between rooms: a little-noted aspect of laboratory procedure
      that may interfere with memory.
AB  - This study investigated the effects of transporting animals from the experimental
      room to the animal facility in between experimental sessions, a procedure
      routinely employed in experimental research, on long-term social recognition
      memory. By using the intruder-resident paradigm, independent groups of Wistar
      rats exposed to a 2-h encounter with an adult intruder were transported from the
      experimental room to the animal facility either 0.5 or 6h after the encounter.
      The following day, residents were exposed to a second encounter with either the
      same or a different (unfamiliar) intruder. Resident's social and non-social
      behaviors were carefully scored and subjected to Principal Component Analysis,
      thus allowing to parcel out variance and relatedness among these behaviors.
      Resident rats transported 6h after the first encounter exhibited reduced amount
      of social investigation towards familiar intruders, but an increase of social
      investigation when exposed to a different intruder as compared to the first
      encounter. These effects revealed a consistent long-lasting (24h) social
      recognition memory in rats. In contrast, resident rats transported 0.5h after the
      first encounter did not exhibit social recognition memory. These results indicate
      that this common, little-noted, laboratory procedure disturbs long-term social
      recognition memory.

PMID- 21729742
TI  - Vascular tube formation and angiogenesis induced by polyvinylpyrrolidone-coated
      silver nanoparticles.
AB  - Silver nanoparticles (AgNPs) are one of the most commonly used nanomaterials due
      to their antibacterial properties. In this study, we examined the effects of
      polyvinylpyrrolidone (PVP)-coated AgNPs (average size 2.3nm) on angiogenesis in
      both an in vivo model and an in vitro endothelial cell line, SVEC4-10. Increased
      angiogenesis was detected around the injection site of AgNP-containing Matrigel
      in vivo. AgNPs also increased the infiltration of endothelial cells and the
      hemoglobin (Hb) content in AgNP-Matrigel plugs implanted into mice. AgNPs induced
      endothelial cell tube formation on growth factor-reduced Matrigel, production of
      reactive oxygen species (ROS), and production of angiogenic factors, such as
      vascular endothelial growth factor (VEGF) and nitric oxide (NO), in SVEC4-10
      cells. In addition, AgNPs promoted the activation of FAK, Akt, ERK1/2, and p38,
      which are all involved in VEGF receptor (VEGFR)-mediated signaling. Finally, AgNP
      treated tumors caused angiogenesis around tumors in B16F10 melanomas after they
      were injected into mice, and the Hb concentration in the tumors increased in a
      concentration-dependent manner with AgNP treatment. Thus, our study suggests that
      exposure to AgNPs can cause angiogenesis through the production of angiogenic
      factors.

PMID- 21729743
TI  - Curcumin and its nano-formulation: the kinetics of tissue distribution and blood
      brain barrier penetration.
AB  - Curcumin has considerable neuro-protective and anti-cancer properties but is
      rapidly eliminated from the body. By optimizing the HPLC method for analysis of
      curcumin, this study evaluates how the ability of curcumin to penetrate organs
      and different regions of the brain is affected by nanoparticulation to increase
      curcumin circulation time in the body. Curcumin-loaded PLGA nanoparticles (C-NPs)
      were prepared by the high-pressure emulsification-solvent evaporation method. The
      mean particle size and entrapment efficiency were 163nm and 46.9%, respectively.
      The release profile of C-NPs was an initial burst effect followed by sustained
      diffusion. In distribution studies, curcumin could be detected in the evaluated
      organs, including liver, heart, spleen, lung, kidney and brain. C-NPs were found
      mainly in the spleen, followed by the lung. Formulation significantly raised the
      curcumin concentration in these organs with increases in the AUC, t(1/2) and MRT
      of curcumin, though this was not apparent in the heart. Curcumin and C-NPs could
      cross the blood-brain barrier (BBB) to enter brain tissue, where it was
      concentrated chiefly in the hippocampus. Nanoparticulation significantly
      prolonged retention time of curcumin in the cerebral cortex (increased by 96%)
      and hippocampus (increased by 83%). These findings provide further understanding
      for the possible therapeutic effects of curcumin and C-NPs in further pre
      clinical and clinical research.

PMID- 21729744
TI  - Preparation and characterization of tri-block poly(lactide)-poly(ethylene glycol)
      poly(lactide) nanogels for controlled release of naltrexone.
AB  - Tri-block poly(lactide)-poly(ethylene glycol)-poly(lactide) (PLA-PEG-PLA)
      copolymers and related acrylated derivative were synthesized and used to prepare
      micelles and nanogels for controlled release of naltrexone. The resulting
      copolymers, micelles and nanogels were characterized by various techniques such
      as proton nuclear magnetic resonance spectroscopy, Fourier transform infrared
      spectroscopy, gel permeation chromatography, fluorescence spectrometry,
      differential scanning calorimetry, photon correlation spectroscopy and scanning
      electron microscopy. The nanogels exhibited high encapsulation efficiency around
      60% and excellent stability for long periods of time. The drug release profiles
      of micelles and nanogels were compared and it was found that the naltrexone
      loaded nanogels offered a steady and long-term release pattern for different
      periods of time up to 35 days, depending on the crosslinker concentration,
      compared to the micelles. The size of nanogels could be manipulated easily in the
      range of 128-200nm by variations in polymer concentration used in the nanogels
      preparation step. From the results obtained it can be concluded that PLA-PEG-PLA
      nanogels can be considered as a promising carrier for drug delivery purpose.

PMID- 21729745
TI  - Parenteral oil-based drospirenone microcrystal suspensions-evaluation of
      physicochemical stability and influence of stabilising agents.
AB  - Drospirenone (DRSP) is a contraceptive drug substance with challenging
      physicochemical properties, due to insufficient solubility in aqueous and oil
      based vehicles as well as low chemical stability in aqueous fluids. Although it
      is one of the most popular orally used progestins, no parenteral long-acting
      contraceptive containing the drug substance is marketed. An oil-based DRSP
      microcrystal suspension (MCS) might be an attractive formulation option. The main
      focus of this study was to investigate the physicochemical stability of such
      preparations. Moreover, syringeability and injectability via autoinjector were
      analysed using a materials testing machine. A high chemical stability of DRSP was
      found in oil-based vehicles. Span((r)) 83, cholesteryl oleate, lecithin, methyl
      cholate, Aerosil((r)) R972 and 200 Pharma were tested for increasing the physical
      stability of DRSP dispersions. Changes in viscosity, rheological properties, and
      solubility were analysed. The intention was to show a stabilising effect of the
      excipients without increasing viscosity and solubility. To evaluate the physical
      stability of DRSP MCS with and without addition of stabilising agents,
      sedimentation and particle growth after storage were examined. Especially, the
      silica derivatives Aerosil((r)) 200 and R972 Pharma influenced the physical
      stability positively.

PMID- 21729746
TI  - Perspectives for nano-biotechnology enabled protection and nutrition of plants.
AB  - Indiscriminate use of pesticides and fertilizers causes environmental pollution,
      emergence of agricultural pests and pathogens, and loss of biodiversity.
      Nanotechnology, by virtue of nanomaterial related properties, has potential agro
      biotechnological applications for alleviation of these problems. The literature
      pertaining to the role of nanotechnology in plant and soil systems demonstrates
      that nanomaterials may assist in a) the controlled release of agrochemicals for
      nutrition and protection against pests and pathogens, b) delivery of genetic
      material, c) sensitive detection of plant disease and pollutants and d)
      protection and formation of soil structure. For instance, porous silica (15nm)
      and biodegradable, polymeric chitosan (78nm) nanoparticles displayed slow release
      of encapsulated pesticide and fertilizer, respectively. Further, nanosized gold
      (5-25nm) delivered DNA to plant cells while iron oxide (30nm) based nanosensors
      detected pesticides at minute levels. These functions assist the development of
      precision farming by minimizing pollution and maximizing the value of farming
      practice.

PMID- 21729747
TI  - Synthetic biology: an emerging research field in China.
AB  - Synthetic biology is considered as an emerging research field that will bring new
      opportunities to biotechnology. There is an expectation that synthetic biology
      will not only enhance knowledge in basic science, but will also have great
      potential for practical applications. Synthetic biology is still in an early
      developmental stage in China. We provide here a review of current Chinese
      research activities in synthetic biology and its different subfields, such as
      research on genetic circuits, minimal genomes, chemical synthetic biology,
      protocells and DNA synthesis, using literature reviews and personal
      communications with Chinese researchers. To meet the increasing demand for a
      sustainable development, research on genetic circuits to harness biomass is the
      most pursed research within Chinese researchers. The environmental concerns are
      driven force of research on the genetic circuits for bioremediation. The research
      on minimal genomes is carried on identifying the smallest number of genomes
      needed for engineering minimal cell factories and research on chemical synthetic
      biology is focused on artificial proteins and expanded genetic code. The research
      on protocells is more in combination with the research on molecular-scale motors.
      The research on DNA synthesis and its commercialisation are also reviewed. As for
      the perspective on potential future Chinese R&D activities, it will be discussed
      based on the research capacity and governmental policy.

PMID- 21729748
TI  - Enterotoxigenic Escherichia coli CS6 gene products and their roles in CS6
      structural protein assembly and cellular adherence.
AB  - Enterotoxigenic Escherichia coli (ETEC) produces a variety of colonization
      factors necessary for attachment to the host cell, among which CS6 is one of the
      most prevalent in ETEC isolates from developing countries. The CS6 operon is
      composed of 4 genes, cssA, cssB, cssC, and cssD. The molecular mechanism of CS6
      assembly and cell surface presentation, and the contribution of each protein to
      the attachment of the bacterium to intestinal cells remain unclear. In the
      present study, a series of css gene-deletion mutants of the CS6 operon were
      constructed in the ETEC genetic background, and their effect on adhesion to host
      cells and CS6 assembly was studied. Each subunit deletion resulted in a reduction
      in the adhesion to intestinal cells to the same level of laboratory E. coli
      strains, and this effect was restored by complementary plasmids, suggesting that
      the 4 proteins are necessary for CS6 expression. Bacterial cell fractionation and
      western blotting of the mutant strains suggested that the formation of a CssA
      CssB-CssC complex is necessary for recognition by CssD and transport of CssA-CssB
      to the outer membrane as a colonization factor.

PMID- 21729749
TI  - Binding of group B streptococcal phosphoglycerate kinase to plasminogen and
      actin.
AB  - The glycolytic enzyme, phosphoglycerate kinase (PGK) of group B streptococci
      (GBS), has previously been identified as expressed on the GBS cell surface. The
      data presented describes the ability of group B streptococcal phosphoglycerate
      kinase (GBS-PGK) to bind to plasminogen and to bind actin. GBS-PGK binding to
      plasminogen was inhibited by the lysine analogue, 6-aminocaproic acid, suggesting
      plasminogen binding is achieved through GBS-PGK lysine residues. In addition to
      GBS-PGK surface expression, GBS-PGK was also found to be released from the
      bacterial cell suggesting GBS-PGK may affect its environment independent of GBS.
      To determine the effect of GBS-PGK on the actin cytoskeleton within a host cell,
      GBS-PGK attached to green fluorescent protein was transfected into and expressed
      in HeLa cells. Transfected GBS-PGK disrupted the actin cytoskeleton resulting in
      a compact or ovoid shaped HeLa cell rather than a typical epithelioid appearance.
      In conclusion, we have shown GBS-PGK binds to plasminogen and actin. We have also
      shown that GBS-PGK can be released from the bacterial cell and that transfected
      GBS-PGK can alter the epithelial cell cytoskeleton.

PMID- 21729750
TI  - Persistent organic pollutants have dose and CAG repeat length dependent effects
      on androgen receptor activity in vitro.
AB  - Recently, the effect of exposure to persistent organic pollutants (POPs) on sperm
      concentration was only seen in men with a short androgen receptor (AR) gene CAG
      repeat. In order to investigate whether these effects could be observed also in
      vitro, we tested the impact of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1
      bis-(4-chlorophenyl)-2,2-dichloroethene (4,4'-DDE) on 5alpha-dihydrotestosterone
      activated ARs containing 16, 22 and 28 CAG repeats, respectively. Single exposure
      to 4,4'-DDE had the most pronounced effect on the AR activity containing 16 CAG
      repeats, whereas 28 CAG was the most sensitive variant when a mixture of the two
      compounds was added. Thus, our in vitro results have confirmed the in vivo data
      indicating a CAG repeat length dependent effect of endocrine disrupters on the AR
      activity.

PMID- 21729751
TI  - Mapping of somatostatin-28 (1-12) in the alpaca diencephalon.
AB  - Using an immunocytochemical technique, we report for the first time the
      distribution of immunoreactive cell bodies and fibers containing somatostatin-28
      (1-12) in the alpaca diencephalon. Somatostatin-28 (1-12)-immunoreactive cell
      bodies were only observed in the hypothalamus (lateral hypothalamic area, arcuate
      nucleus and ventromedial hypothalamic nucleus). However, immunoreactive fibers
      were widely distributed throughout the thalamus and hypothalamus. A high density
      of such fibers was observed in the central medial thalamic nucleus, laterodorsal
      thalamic nucleus, lateral habenular nucleus, mediodorsal thalamic nucleus,
      paraventricular thalamic nucleus, reuniens thalamic nucleus, rhomboid thalamic
      nucleus, subparafascicular thalamic nucleus, anterior hypothalamic area, arcuate
      nucleus, dorsal hypothalamic area, around the fornix, lateral hypothalamic area,
      lateral mammilary nucleus, posterior hypothalamic nucleus, paraventricular
      hypothalamic nucleus, suprachiasmatic nucleus, supraoptic hypothalamic nucleus,
      and in the ventromedial hypothalamic nucleus. The widespread distribution of
      somatostatin-28 (1-12) in the thalamus and hypothalamus of the alpaca suggests
      that the neuropeptide could be involved in many physiological actions.

PMID- 21729752
TI  - Functional studies on twenty novel naturally occurring melanocortin-4 receptor
      mutations.
AB  - The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor critically
      involved in regulating energy balance. MC4R activation results in decreased food
      intake and increased energy expenditure. Genetic and pharmacological studies
      demonstrated that the MC4R regulation of energy balance is conserved from fish to
      mammals. In humans, more than 150 naturally occurring mutations in the MC4R gene
      have been identified. Functional study of mutant MC4Rs is an important component
      in proving the causal link between MC4R mutation and obesity as well as the basis
      of personalized medicine. In this article, we studied 20 MC4R mutations that were
      either not characterized or not fully characterized. We showed that 11 mutants
      had decreased or absent cell surface expression. D126Y was defective in ligand
      binding. Three mutants were constitutively active but had decreased cell surface
      expression. Eleven mutants had decreased basal signaling, with two mutants
      defective only in this parameter, suggesting that impaired basal signaling might
      also be a cause of obesity. Five mutants had normal functions. In summary, we
      provided detailed functional data for further studies on identifying therapeutic
      approaches for personalized medicine to treat patients harboring these mutations.

PMID- 21729753
TI  - Endocrine-active chemicals in mammary cancer causation and prevention.
AB  - Endocrine-active chemicals alter or mimic physiological hormones. These compounds
      are reported to originate from a wide variety of sources, and recent studies have
      shown widespread human exposure to several of these compounds. Given the role of
      the sex steroid hormone, estradiol, in human breast cancer causation, endocrine
      active chemicals which interfere with estrogen signaling constitute one potential
      factor contributing to the high incidence of breast cancer. Thus, the aim of this
      review is to examine several common endocrine-active chemicals and their
      respective roles in breast cancer causation or prevention. The plastic component,
      bisphenol A (BPA), the synthetic estrogen, diethylstilbestrol (DES), the by
      product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the
      soy component, genistein, and the red grape phytoalexin, resveratrol, have some
      degree of structural similarities to each other and estradiol. However, despite
      these structural similarities, the in vitro and in vivo properties of each of
      these chemicals vary greatly in terms of breast cancer causation and prevention.
      Early life exposure to BPA and DES increases rodent susceptibility to chemically
      induced mammary carcinogenesis, presumably through retardation of normal mammary
      gland maturation and/or disrupting the ratio of cell proliferation and apoptosis
      in the mammary gland. On the other hand, early exposures to genistein and
      resveratrol protect rodents against chemically induced and spontaneous mammary
      cancers. This is reported to occur through the ability of genistein and
      resveratrol to accelerate mammary gland maturation. Interestingly, TCDD, which is
      the most structurally dissimilar to the above chemicals and functions as an anti
      estrogen, also increases chemically induced mammary carcinogenesis through
      retardation of mammary gland maturation. This article is part of a Special Issue
      entitled 'Endocrine disruptors'.

PMID- 21729754
TI  - Outline of a concept for organismic systems biology.
AB  - For several decades experimental biology and medicine have both been accompanied
      by a dichotomy between reductionistic and anti-reductionistic approaches. In the
      present paper it is proposed that this dichotomy can be overcome if it is
      accepted that research on different organizational levels of the organism is
      necessary. The relevance of such an approach becomes much clearer using an
      appropriate concept of the organism. The proposed concept is called "organismic
      systems biology" and is a compilation of three related theories, which are
      basically in line with considerations of many other organismic thinkers. However,
      it is argued, that this integrated concept is able to clarify basic assumptions
      of organismic. The theories are: the systems approach of Paul Weiss, the
      developmental systems theory and the theory of increasing autonomy in evolution.
      The hypothesis is that the different levels of organismic functions, which are
      described by these theories, are necessarily interrelated, thus generating the
      autonomy of the organism. This principle of interrelation needs to be regarded in
      scientific reasoning and can be crucial for solving many medical problems.

PMID- 21729755
TI  - Single subunit type of ferritin from visceral mass of Saccostrea cucullata:
      cloning, expression and cisplatin-subunit analysis.
AB  - Ferritin, the iron storage protein, plays a key role in iron metabolism. Here, we
      have cloned an inducible ferritin cDNA with 516 bp within the open reading frame
      fragment from the visceral mass of Saccostrea cucullata. The subunit sequence of
      the ferritin was predicted to be a polypeptide of 171 amino acids with a
      molecular weight (MW) of 19.9182 kDa and an isoelectric point of 5.24. The cDNA
      sequence of S. cucullata ferritin was constructed into a pET-32a expression
      system for expressing its relative protein efficiently in the Escherichia coli
      BL21 strain under isopropyl-beta-D-thiogalactoside (IPTG) induction. The
      recombinant ferritin, which was further purified on a Ni-NTA resin column and
      digested with enterokinase, was detected as a single subunit of approximately MW
      20 kDa using both SDS-PAGE and mass spectrometry. S. cucullata ferritin (ScFer)
      showed 98% identity with Crassostrea gigas ferritin at the amino acid level. The
      secondary structure and phosphorylation sites of deduced amino acids were
      predicted with ExPASy proteomics tools and the NetPhos 2.0 server, respectively,
      and the subunit space structure of recombinant S. cucullata ferritin (rScFer) was
      built using the molecular operating environmental software system. The results of
      both in-gel digestion and identification using MALDI-TOF MS/MS showed that the
      recombinant protein was ScFer. ICP-MS indicated that rScFer subunit can directly
      bind to cisplatin[cis-Diaminedichloroplatinum(CDDP)], giving approximately 22.9
      CDDP/ferritin subunit for forming a novel complex of CDDP-subunit, which suggests
      that it constructs a nanometer CDDP core-ferritin for developing a new drug of
      anti-cancer. The results of both the real-time PCR and Western blotting showed
      that the expression of ScFer mRNA was up-regulated in the oyster under the stress
      of Cd(2+). In addition, the expression increment of ScFer mRNA under bacterial
      challenge indicated that ferritin participated in the immune response of S.
      cucullata. The recombinant ScFer should prove to be useful for further study of
      the structure and function of ferritin in S. cucullata.

PMID- 21729756
TI  - Utilizing temporal information in fMRI decoding: classifier using kernel
      regression methods.
AB  - This paper describes a general kernel regression approach to predict experimental
      conditions from activity patterns acquired with functional magnetic resonance
      image (fMRI). The standard approach is to use classifiers that predict conditions
      from activity patterns. Our approach involves training different regression
      machines for each experimental condition, so that a predicted temporal profile is
      computed for each condition. A decision function is then used to classify the
      responses from the testing volumes into the corresponding category, by comparing
      the predicted temporal profile elicited by each event, against a canonical
      hemodynamic response function. This approach utilizes the temporal information in
      the fMRI signal and maintains more training samples in order to improve the
      classification accuracy over an existing strategy. This paper also introduces
      efficient techniques of temporal compaction, which operate directly on kernel
      matrices for kernel classification algorithms such as the support vector machine
      (SVM). Temporal compacting can convert the kernel computed from each fMRI volume
      directly into the kernel computed from beta-maps, average of volumes or spatial
      temporal kernel. The proposed method was applied to three different datasets. The
      first one is a block-design experiment with three conditions of image stimuli.
      The method outperformed the SVM classifiers of three different types of temporal
      compaction in single-subject leave-one-block-out cross-validation. Our method
      achieved 100% classification accuracy for six of the subjects and an average of
      94% accuracy across all 16 subjects, exceeding the best SVM classification
      result, which was 83% accuracy (p=0.008). The second dataset is also a block
      design experiment with two conditions of visual attention (left or right). Our
      method yielded 96% accuracy and SVM yielded 92% (p=0.005). The third dataset is
      from a fast event-related experiment with two categories of visual objects. Our
      method achieved 77% accuracy, compared with 72% using SVM (p=0.0006).

PMID- 21729757
TI  - Fronto-parietal hypo-activation during working memory independent of structural
      abnormalities: conjoint fMRI and sMRI analyses in adolescent offspring of
      schizophrenia patients.
AB  - Adolescent offspring of schizophrenia patients (HR-S) are an important group in
      whom to study impaired brain function and structure, particularly of the frontal
      cortices. Studies of working memory have suggested behavioral deficits and fMRI
      measured hypoactivity in fronto-parietal regions in these subjects. Independent
      structural MRI (sMRI) studies have suggested exaggerated frontal gray matter
      decline. Therefore the emergent view is that fronto-parietal deficits in function
      and structure characterize HR-S. However, it is unknown if fronto-parietal sub
      regions in which fMRI-measured hypo-activity might be observed are precisely
      those regions of the cortex in which gray matter deficits are also observed. To
      investigate this question we conducted conjoint analyses of fronto-parietal
      function and structure in HR-S (n=19) and controls (n=24) with no family history
      of psychoses using fMRI data during a continuous working memory task (2 back),
      and sMRI collected in the same session. HR-S demonstrated significantly reduced
      BOLD activation in left dorso-lateral prefrontal cortex (BA 9/46) and bilateral
      parietal cortex (BA 7/40). Sub-regions of interest were created from the
      significant fronto-parietal functional clusters. Analyses of gray matter volume
      from volume-modulated gray matter segments in these clusters did not reveal
      significant gray matter differences between groups. The results suggest that
      functional impairments in adolescent HR-S can be independent of impairments in
      structure, suggesting that the relationship between impaired function and
      structure is complex. Further studies will be needed to more closely assess
      whether impairments in function and structure provide independent or interacting
      pathways of vulnerability in this population.

PMID- 21729758
TI  - TWave: high-order analysis of functional MRI.
AB  - The traditional approach to functional image analysis models images as matrices
      of raw voxel intensity values. Although such a representation is widely utilized
      and heavily entrenched both within neuroimaging and in the wider data mining
      community, the strong interactions among space, time, and categorical modes such
      as subject and experimental task inherent in functional imaging yield a dataset
      with "high-order" structure, which matrix models are incapable of exploiting.
      Reasoning across all of these modes of data concurrently requires a high-order
      model capable of representing relationships between all modes of the data in
      tandem. We thus propose to model functional MRI data using tensors, which are
      high-order generalizations of matrices equivalent to multidimensional arrays or
      data cubes. However, several unique challenges exist in the high-order analysis
      of functional medical data: naive tensor models are incapable of exploiting
      spatiotemporal locality patterns, standard tensor analysis techniques exhibit
      poor efficiency, and mixtures of numeric and categorical modes of data are very
      often present in neuroimaging experiments. Formulating the problem of image
      clustering as a form of Latent Semantic Analysis and using the WaveCluster
      algorithm as a baseline, we propose a comprehensive hybrid tensor and wavelet
      framework for clustering, concept discovery, and compression of functional
      medical images which successfully addresses these challenges. Our approach
      reduced runtime and dataset size on a 9.3GB finger opposition motor task fMRI
      dataset by up to 98% while exhibiting improved spatiotemporal coherence relative
      to standard tensor, wavelet, and voxel-based approaches. Our clustering technique
      was capable of automatically differentiating between the frontal areas of the
      brain responsible for task-related habituation and the motor regions responsible
      for executing the motor task, in contrast to a widely used fMRI analysis program,
      SPM, which only detected the latter region. Furthermore, our approach discovered
      latent concepts suggestive of subject handedness nearly 100* faster than standard
      approaches. These results suggest that a high-order model is an integral
      component to accurate scalable functional neuroimaging.

PMID- 21729759
TI  - Species tree inference in a recent radiation of orioles (Genus Icterus): multiple
      markers and methods reveal cytonuclear discordance in the northern oriole group.
AB  - Recent computational advances provide novel opportunities to infer species trees
      based on multiple independent loci. Thus, single gene trees no longer need
      suffice as proxies for species phylogenies. Several methods have been developed
      to deal with the challenges posed by incomplete and stochastic lineage sorting.
      In this study, we employed four Bayesian methods to infer the phylogeny of a
      clade of 11 recently diverged oriole species within the genus Icterus. We
      obtained well-resolved and mostly congruent phylogenies using a set of seven
      unlinked nuclear intron loci and sampling multiple individuals per species. Most
      notably, Bayesian concordance analysis generally agreed well with concatenation;
      the two methods agreed fully on eight of nine nodes. The coalescent-based method
      *BEAST further supported six of these eight nodes. The fourth method used, BEST,
      failed to converge despite exhaustive efforts to optimize the tree search.
      Overall, the results obtained by new species tree methods and concatenation
      generally corroborate our findings from previous analyses and data sets. However,
      we found striking disagreement between mitochondrial and nuclear DNA involving
      relationships within the northern oriole group. Our results highlight the danger
      of reliance on mtDNA alone for phylogenetic inference. We demonstrate that in
      spite of low variability and incomplete lineage sorting, multiple nuclear loci
      can produce largely congruent phylogenies based on multiple species tree methods,
      even for very closely-related species.

PMID- 21729761
TI  - Statins and outcome after hospitalization for COPD exacerbation: a prospective
      study.
AB  - BACKGROUND: Retrospective studies have shown that the use of statins is
      associated with reduced mortality and decreased hospitalizations from COPD, but
      data from prospective studies are lacking. METHODS: We followed-up prospectively
      245 patients admitted to hospital for exacerbations of COPD (ECOPD) with monthly
      evaluations for one year. The role of statins on outcomes was evaluated by Cox
      regression analysis after proper adjustments for age, gender, BMI, current
      smoking status, Charlson comorbidity index and COPD stage. Health-related quality
      of life (HRQoL) was evaluated by Saint George's Respiratory Questionnaire.
      RESULTS: There was no effect of statins on either 30-day or 1-year mortality.
      Patients receiving statins presented a lower total number of ECOPD during the 1
      year follow up (2.1 +/- 2.7 vs. 2.8 +/- 3.2 ECOPD/patient respectively, p =
      0.037). After proper adjustments, the use of statins was associated with a lower
      risk for ECOPD [HR: 0.656 (95% CI: 0.454-0.946)] and severe ECOPD [HR: 0.608
      (95%CI: 0.381-0.972)]. The group of statins presented better improvement in HRQoL
      at 2, 6 and 12 months (p < 0.001). CONCLUSIONS: The use of statins in patients
      hospitalized for ECOPD was associated with a lower risk for subsequent ECOPD and
      severe ECOPD and improved HRQoL. These data support a possible beneficial role
      for these agents in COPD.

PMID- 21729760
TI  - Rapid tip growth: insights from pollen tubes.
AB  - Pollen tubes extend rapidly in an oscillatory manner by the extreme form of
      polarized growth, tip growth, and provide an exciting system for studying the
      spatiotemporal control of polarized cell growth. The Rho-family ROP GTPase is a
      key signaling molecule in this growth control and is periodically activated at
      the apical plasma membrane to spatially define the apical growth region and
      temporally precede the burst of growth. The spatiotemporal dynamics of ROP GTPase
      is interconnected with actin dynamics and polar exocytosis that is required for
      tip-targeted membrane and wall expansion. Recent advances in the study of the
      mechanistic interlinks between ROP-centered signaling and spatiotemporal dynamics
      of cell membrane and wall remodeling will be discussed.

PMID- 21729762
TI  - Seasonal changes of free amino acids and thermal hysteresis in overwintering
      heteropteran insect, Pyrrhocoris apterus.
AB  - Overwintering adults of Pyrrhocoris apterus do not tolerate freezing of their
      body fluids and rely on a supercooling strategy and seasonal accumulation of
      polyols to survive at subzero body temperatures. We sampled the adults monthly in
      the field during the cold season 2008-2009 and found active thermal hysteresis
      factors (THFs) in hemolymph of winter-sampled adults. The hysteresis between the
      equilibrium melting and freezing points ranged from 0.18 degrees C to 0.30
      degrees C. No signs of THFs activity were found in the autumn- and spring-sampled
      insects. The total free amino acid pool almost doubled during winter time. The
      sum concentrations of 27 free amino acids ranged between 35 and 40mM in whole
      body water and 40-45mM in hemolymph during December-February. Two amino acids,
      Pro and alpha-Ala most significantly contributed to the seasonal increase, while
      Gln showed the most dramatic seasonal decrease. Moderate levels of amino acid
      accumulation in overwintering P. apterus suggest that they are by-products of
      protein degradation and pentose pathway activity during the state of metabolic
      suppression imposed by diapause and low body temperature. Potential colligative
      effects of accumulated amino acids, extending the supercooling capacity of
      overwintering P. apterus, are negligible. Non-colligative effects require further
      study.

PMID- 21729763
TI  - Polarization sensitive optical coherence tomography in the human eye.
AB  - Optical coherence tomography (OCT) has become a well established imaging tool in
      ophthalmology. The unprecedented depth resolution that is provided by this
      technique yields valuable information on different ocular tissues ranging from
      the anterior to the posterior eye segment. Polarization sensitive OCT (PS-OCT)
      extends the concept of OCT and utilizes the information that is carried by
      polarized light to obtain additional information on the tissue. Several
      structures in the eye (e.g. cornea, retinal nerve fiber layer, retinal pigment
      epithelium) alter the polarization state of the light and show therefore a tissue
      specific contrast in PS-OCT images. First this review outlines the basic concepts
      of polarization changing light-tissue interactions and gives a short introduction
      in PS-OCT instruments for ophthalmic imaging. In a second part a variety of
      different applications of this technique are presented in ocular imaging that are
      ranging from the anterior to the posterior eye segment. Finally the benefits of
      the method for imaging different diseases as, e.g., age related macula
      degeneration (AMD) or glaucoma is demonstrated.

PMID- 21729764
TI  - Defining EMS and ENU dose-response relationships using the Pig-a mutation assay
      in rats.
AB  - In recent years, experimental evidence has accumulated that supports the
      existence of sublinear dose-response relationships at low doses of DNA reactive
      mutagens. However, creating the in vivo data necessary to allow for a more
      detailed dose-response modeling with the currently available tools might not
      always be practical. The purpose of the current work was to evaluate the utility
      of the Pig-a gene mutation assay to rapidly identify dose-response relationships
      for direct acting genotoxicants. The induction of mutations in the peripheral
      blood of rats was evaluated following 28 days of exposure down to low doses of
      the direct acting alkylating agents ethyl methane sulfonate (EMS) and
      ethylnitrosourea (ENU). Using statistical modeling based on the 28-day studies, a
      threshold for mutation induction for EMS was estimated to be 21.9mg/kg, whereas
      for the more potent ENU, the threshold was estimated to be 0.88mg/kg. Comparing
      mutation frequencies from acute and sub-chronic dosing indicated less than
      additive dose-response relationships, further confirming the possibility of a
      threshold dose-response relationship for both compounds. In conclusion, the work
      presented provides evidence that the Pig-a assay might be a practical alternative
      to other in vivo mutation assays when assessing dose-response relationships for
      direct acting mutagens and that an experimental approach using fractionated
      dosing could be used to substantiate a biological mechanism responsible for the
      observation of a sublinear dose-response relationship.

PMID- 21729765
TI  - Development of a TaqMan based real-time PCR assay for detection of Clonorchis
      sinensis DNA in human stool samples and fishes.
AB  - Clonorchiasis caused by the oriental liver fluke Clonorchis sinensis is a fish
      borne zoonosis endemic in a number of countries. This article describes the
      development of a TaqMan based real-time PCR assay for detection of C. sinensis
      DNA in human feces and in fishes. Primers targeting the first internal
      transcribed spacer (ITS-1) sequence of the fluke were highly specific for C.
      sinensis, as evidenced by the negative amplification of closely related
      trematodes in the test with the exception of Opisthorchis viverrini. The
      detection limit of the assay was 1pg of purified genomic DNA, 5EPG (eggs per gram
      feces) or one metacercaria per gram fish filet. The assay was evaluated by
      testing 22 human fecal samples and 37 fish tissues microscopically determined
      beforehand, and the PCR results were highly in agreement with the microscopic
      results. This real-time PCR assay provides a useful tool for the sensitive
      detection of C. sinensis DNA in human stool and aquatic samples in China and
      other endemic countries where O. viverrini and Opisthorchis felineus are absent.

PMID- 21729766
TI  - Aquatic animal models of human disease: selected papers from the 5th conference.

PMID- 21729767
TI  - Incorporation of historical data in the analysis of randomized therapeutic
      trials.
AB  - Historical studies provide a valuable source of information for the motivation
      and design of later trials. Bayesian techniques offer possibilities for the
      quantitative inclusion of prior knowledge within the analysis of current trial
      data. Combining information from previous studies into an informative prior
      distribution is, however, a delicate case. The power prior distribution is a tool
      to estimate the effect of an intervention in a current study sample, while
      accounting for the information provided by previous research. In this study we
      evaluate the use of the power prior distribution, illustrated with data from a
      large randomized clinical trial on the effect of ST-wave analysis in intrapartum
      fetal monitoring. We advocate the use of a power prior distribution with pre
      specified fixed study weights based on differences in study characteristics. We
      propose obtaining a ranking of the historical studies via expert elicitation,
      based on relevance for the current study, and specify study weights accordingly.

PMID- 21729768
TI  - Associations of multi-locus polymorphisms in an immune network with
      susceptibility to uncomplicated Plasmodium falciparum malaria in Daraweesh
      village, Eastern Sudan.
AB  - Susceptibility to uncomplicated malaria (UM), as to other forms of the disease,
      is genetically determined. Over 9-years of clinical and parasitological follow up
      of inhabitants of Daraweesh, in Eastern Sudan, the relative susceptibility to UM
      was estimated in terms of number of episodes experienced by each individual.
      Previously, we reported that the levels of IgG2 and IgG3 to Pf332-C231 malaria
      antigen are negatively correlated with number of malaria episodes. In addition,
      four molecular markers for malaria susceptibility (CRP -286, GM/KM haplotypes,
      FcgammaRIIa131 and HbAS) were tested. In this study, the above data were combined
      and reanalysed. The CRP -286A allele and GM 1,17 5,13,14,6 phenotype were
      previously found to be associated with increased susceptibility to malaria;
      however, individuals have both polymorphism together were not more susceptible to
      UM than the non-carriers of the same double polymorphism. The FcgammaRIIa-RR131
      and HbAA genotypes taken individually or as double polymorphism were not
      associated with malaria susceptibility; however, their combination with any or
      both of the former polymorphisms was mostly associated with increased
      susceptibility to malaria. None of the four markers were associated with the
      levels of IgG2 and IgG3 against Pf332-C231. In conclusion, while our data support
      the polygenic nature of susceptibility to UM and highlighted the role of immune
      markers polymorphisms, the combinations of these markers were not predictable,
      i.e. the combination of the susceptibility markers will not necessarily render
      the carriers more susceptible to UM.

PMID- 21729769
TI  - Genetic variability in the major capsid L1 protein of human papillomavirus type
      16 (HPV-16) and 18 (HPV-18).
AB  - HPV-16 and HPV-18 infections result in nearly 73% of cervical cancers worldwide.
      The L1 protein comprising HPV vaccine formulations elicit high-titre neutralizing
      antibodies. The aim of this study was to detect L1 HPV-16 and HPV-18 gene
      polymorphisms and analyze intratypic variations. HPV-16 (n = 29) and HPV-18 (n =
      5) L1 gene sequences were obtained from cervical samples harvested from Italian
      women. Phylogenetic trees were constructed using the Neighbor-Joining and the
      Kimura 2-parameters methods (MEGA software). To estimate selection pressures
      acting on the L1 gene, codon-specific non-synonymous (d(N)) and synonymous (d(S))
      substitutions were inferred using the Nei-Gojobori method and Jukes-Cantor model
      (MEGA software) and integrated analyses carried out using SLAC, FEL and REL
      methodologies. All the HPV-16 L1 sequences analyzed fell into the European branch
      (99.4-99.7% similarity). Thirty-four single nucleotide changes were observed and
      18 (52.9%) were non-synonymous mutations (7/18 were identified in sequences
      encoding an immunodominant loop and one occurred in the sequence encoding the
      alpha-4 domain associated with VLP conformation). There was no evidence of
      positive selection in the sequence alignment of L1 HPV-16 genes (P-value < 0.1).
      One mutation was identified in a negatively selected codon. HPV-18 L1 analyzed
      sequences fell into two phylogenetic branches: the HPV-18 European branch (99.5
      100% similarity) and the HPV-18 African branch (99.8% similarity). Nine single
      nucleotide changes were observed and 4/9 (44.5%) of these nucleotide mutations
      were non-synonymous and one was present in a sequence encoding the immunodominant
      FG loop. There was no evidence of positive selection in the sequence alignment of
      L1 HPV-18 genes (P-value < 0.1). This study identified polymorphisms of undefined
      biological activity in HPV-16 and HPV-18 L1 sequences. Information regarding the
      genetic diversity of HPV-16 and HPV-18 L1 gene sequences may help define the
      oncogenic potential of respective strains and to better understand immune escape
      mechanisms.

PMID- 21729770
TI  - Systemic inflammation impairs respiratory chemoreflexes and plasticity.
AB  - Many lung and central nervous system disorders require robust and appropriate
      physiological responses to assure adequate breathing. Factors undermining the
      efficacy of ventilatory control will diminish the ability to compensate for
      pathology, threatening life itself. Although most of these same disorders are
      associated with systemic and/or neuroinflammation, and inflammation affects
      neural function, we are only beginning to understand interactions between
      inflammation and any aspect of ventilatory control (e.g. sensory receptors,
      rhythm generation, chemoreflexes, plasticity). Here we review available evidence,
      and present limited new data suggesting that systemic (or neural) inflammation
      impairs two key elements of ventilatory control: chemoreflexes and respiratory
      motor (versus sensory) plasticity. Achieving an understanding of mechanisms
      whereby inflammation undermines ventilatory control is fundamental since
      inflammation may diminish the capacity for natural, compensatory responses during
      pathological states, and the ability to harness respiratory plasticity as a
      therapeutic strategy in the treatment of devastating breathing disorders, such as
      during cervical spinal injury or motor neuron disease.

PMID- 21729771
TI  - Ventilatory behavior and carotid body morphology of Brown Norway and Sprague
      Dawley rats.
AB  - Differences in acute ventilatory behavior are associated with carotid body (CB)
      structural and immunohistologic profiles in some, but not all, reports. Brown
      Norway (BN) rats exhibit lower acute ventilatory responses to hypoxia and
      hypercapnia compared to Sprague Dawley (SD) rats. We hypothesized that BN rats
      possess CB with fewer glomus cells. Ventilation was recorded in 6-month-old BN
      and SD rats exposed to hypoxia-reoxygenation and hypercapnia. Extracted CBs were
      examined using H&E staining, and immunohistochemistry with antibodies specific
      for tyrosine hydroxylase (TH), neural nitric oxide synthase (nNOS), and pyruvate
      dehydrogenase (PD). Sections were analyzed for cell and immunostaining density.
      SD displayed greater hypoxic and hypercapnic responses, and post-hypoxic short
      term potentiation, whereas BN exhibited post-hypoxic frequency decline. Contrary
      to our hypothesis, BN demonstrated a denser arrangement of glomus cells with a
      larger TH stained area (31.7% BN, 22.6% SD; p<0.0001), and nNOS stained area
      (37.3% BN, 32.1%; SD; p=0.01). Hence, respiratory phenotype does not correlate
      intuitively with these anatomic features.

PMID- 21729772
TI  - Chest wall kinematics and breathlessness during unsupported arm exercise in COPD
      patients.
AB  - We hypothesised that chest wall displacement inappropriate to increased
      ventilation contributes to dyspnoea more than dynamic hyperinflation or
      dyssynchronous breathing during unsupported arm exercise (UAE) in COPD patients.
      We used optoelectronic plethysmography to evaluate operational volumes of chest
      wall compartments, the upper rib cage, lower rib cage and abdomen, at 80% of peak
      incremental exercise in 13 patients. The phase shift between the volumes of upper
      and lower rib cage (RC) was taken as an index of RC distortion. With UAE, no
      chest wall dynamic hyperinflation was found; sometimes the lower RC paradoxed
      inward while in other patients it was the upper RC. Phase shift did not correlate
      with dyspnoea (by Borg scale) at any time, and chest wall displacement was in
      proportion to increased ventilation. In conclusions neither chest wall dynamic
      hyperinflation nor dyssynchronous breathing per se were major contributors to
      dyspnoea. Unlike our prediction, chest wall expansion and ventilation were
      adequately coupled with each other.

PMID- 21729773
TI  - Commentary on: Preoperative shockwave treatment enhances ischemic tissue survival
      in a rat flap model.

PMID- 21729774
TI  - Production of high amounts of 3-hydroxypropionaldehyde from glycerol by
      Lactobacillus reuteri with strongly increased biocatalyst lifetime and
      productivity.
AB  - 3-hydroxypropionaldehyde (3HPA) is a promising versatile substance derived from
      the renewable feedstock glycerol. It is a product of glycerol metabolism in
      Lactobacillus reuteri. Because of toxic effects, the biotechnological production
      is poor. In this work the biocatalyst lifetime and product formation could be
      drastically increased. In the established two-step process already applied, cells
      are grown in the first step under anaerobic conditions, and in the second step
      the immobilised or suspended biocatalyst is used for 3HPA-production under strict
      anaerobic conditions. In the first step it was possible to reach a biomass
      concentration of 5.5g CDW/L (OD(600)~23.4). In the second step, normally, 3HPA
      accumulates to a toxic concentration and the reaction stops in less than 60min
      because of the interaction of 3HPA with cell components. To prevent this, the
      toxic product is bound to the newly found scavenger carbohydrazide to form the
      hydrazone. For the first time it was possible to recycle the immobilised
      biocatalyst for at least ten cycles (overall life time>33hours) in a repeated
      batch biotransformation with an overall production of 67g 3HPA. The optimal pH
      value was between 6.8 and 7.2 at an optimal temperature of 40-45 degrees C. In a
      single batch biotransformation with suspended resting cells it was possible to
      produce 150g/L 3HPA as carbohydrazone at an overall productivity of 10.7gL(
      1)hours(-1). In a single fed-batch biotransformation at 45 degrees C 138g/L
      glycerol was converted into 108g/L 3HPA with an overall productivity of 21.6gL(
      1)hours(-1). This is the highest 3HPA concentration and productivities reported
      so far for the microbial production of 3HPA from glycerol.

PMID- 21729775
TI  - GelMap-a novel software tool for building and presenting proteome reference maps.
AB  - Protein separation by two-dimensional gel electrophoresis is of central
      importance for proteomics. Upon combination with systematic protein
      identifications by mass spectrometry, large data sets are routinely generated in
      several proteome laboratories which can be used as "reference maps" for future
      analyses of analogous biochemical fractions. Here we present GelMap, a novel
      software tool for the building presentation and evaluation of proteomic reference
      maps. Variable frames are introduced in order to group proteins into functional
      categories on three levels or into categories according to differential abundance
      during comparative proteome analyses. The software is easy to handle as it only
      requires uploading two digital files to a web site. An additional file including
      detailed information on all proteins can be combined with the primary map. Two
      different gel-based projects are presented to illustrate the capacity of GelMap
      for proteome annotation and evaluation.

PMID- 21729776
TI  - A feedforward loop links Gaucher and Parkinson's diseases?
AB  - Mutations in the GBA gene that encodes glucocerebrosidase cause the lysosomal
      storage disorder Gaucher disease but also increase the risk for Parkinson's
      disease. Mazzulli et al. (2011) uncover a possible mechanism to explain this
      connection: loss of glucocerebrosidase creates a positive feedback loop of
      reduced lysosomal function and alpha-synuclein accumulation, ultimately leading
      to neurodegeneration.

PMID- 21729777
TI  - A YY1 bridge for X inactivation.
AB  - Xist RNA inactivates one mammalian X chromosome (the Xi) by associating with it
      in cis. The mechanism of this interaction is unresolved. Jeon and Lee (2011) now
      show that YY1 binds both Xist RNA and DNA, thereby providing a mechanism to
      anchor Xist to the Xi and facilitate X chromosome inactivation.

PMID- 21729778
TI  - A flip turn for membrane protein insertion.
AB  - The transmembrane domains in a membrane protein must be recognized and correctly
      oriented before their insertion into the lipid bilayer. Devaraneni et al. (2011)
      generate snapshots at different stages of membrane protein biogenesis, revealing
      a dynamic set of steps that imply an unexpectedly flexible membrane insertion
      machinery.

PMID- 21729779
TI  - Development and evolution of the human neocortex.
AB  - The size and surface area of the mammalian brain are thought to be critical
      determinants of intellectual ability. Recent studies show that development of the
      gyrated human neocortex involves a lineage of neural stem and transit-amplifying
      cells that forms the outer subventricular zone (OSVZ), a proliferative region
      outside the ventricular epithelium. We discuss how proliferation of cells within
      the OSVZ expands the neocortex by increasing neuron number and modifying the
      trajectory of migrating neurons. Relating these features to other mammalian
      species and known molecular regulators of the mouse neocortex suggests how this
      developmental process could have emerged in evolution.

PMID- 21729780
TI  - Glioma stem cell proliferation and tumor growth are promoted by nitric oxide
      synthase-2.
AB  - Malignant gliomas are aggressive brain tumors with limited therapeutic options,
      and improvements in treatment require a deeper molecular understanding of this
      disease. As in other cancers, recent studies have identified highly tumorigenic
      subpopulations within malignant gliomas, known generally as cancer stem cells.
      Here, we demonstrate that glioma stem cells (GSCs) produce nitric oxide via
      elevated nitric oxide synthase-2 (NOS2) expression. GSCs depend on NOS2 activity
      for growth and tumorigenicity, distinguishing them from non-GSCs and normal
      neural progenitors. Gene expression profiling identified many NOS2-regulated
      genes, including the cell-cycle inhibitor cell division autoantigen-1 (CDA1).
      Further, high NOS2 expression correlates with decreased survival in human glioma
      patients, and NOS2 inhibition slows glioma growth in a murine intracranial model.
      These data provide insight into how GSCs are mechanistically distinct from their
      less tumorigenic counterparts and suggest that NOS2 inhibition may be an
      efficacious approach to treating this devastating disease.

PMID- 21729781
TI  - Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of
      DDK and S-CDK kinases.
AB  - Proper eukaryotic DNA replication requires temporal separation of helicase
      loading from helicase activation and replisome assembly. Using an in vitro assay
      for eukaryotic origin-dependent replication initiation, we investigated the
      control of these events. After helicase loading, we found that the Dbf4-dependent
      Cdc7 kinase (DDK) but not S phase cyclin-dependent kinase (S-CDK) is required for
      the initial origin recruitment of Sld3 and the Cdc45 helicase-activating protein.
      Likewise, in vivo, DDK drives early-firing-origin recruitment of Cdc45 before
      activation of S-CDK. After S-CDK activation, a second helicase-activating protein
      (GINS) and the remainder of the replisome are recruited to the origin. Finally,
      recruitment of lagging but not leading strand DNA polymerases depends on Mcm10
      and DNA unwinding. Our studies identify distinct roles for DDK and S-CDK during
      helicase activation and support a model in which the leading strand DNA
      polymerase is recruited prior to origin DNA unwinding and RNA primer synthesis.

PMID- 21729782
TI  - Human mediator subunit MED26 functions as a docking site for transcription
      elongation factors.
AB  - Promoter-proximal pausing by initiated RNA polymerase II (Pol II) and regulated
      release of paused polymerase into productive elongation has emerged as a major
      mechanism of transcription activation. Reactivation of paused Pol II correlates
      with recruitment of super-elongation complexes (SECs) containing ELL/EAF family
      members, P-TEFb, and other proteins, but the mechanism of their recruitment is an
      unanswered question. Here, we present evidence for a role of human Mediator
      subunit MED26 in this process. We identify in the conserved N-terminal domain of
      MED26 overlapping docking sites for SEC and a second ELL/EAF-containing complex,
      as well as general initiation factor TFIID. In addition, we present evidence
      consistent with the model that MED26 can function as a molecular switch that
      interacts first with TFIID in the Pol II initiation complex and then exchanges
      TFIID for complexes containing ELL/EAF and P-TEFb to facilitate transition of Pol
      II into the elongation stage of transcription.

PMID- 21729783
TI  - Building enhancers from the ground up: a synthetic biology approach.
AB  - A challenge of the synthetic biology approach is to use our understanding of a
      system to recreate a biological function with specific properties. We have
      applied this framework to bacterial enhancers, combining a driver, transcription
      factor binding sites, and a poised polymerase to create synthetic modular
      enhancers. Our findings suggest that enhancer-based transcriptional control
      depends critically and quantitatively on DNA looping, leading to complex
      regulatory effects when the enhancer cassettes contain additional transcription
      factor binding sites for TetR, a bacterial transcription factor. We show through
      a systematic interplay of experiment and thermodynamic modeling that the level of
      gene expression can be modulated to convert a variable inducer concentration
      input into discrete or step-like output expression levels. Finally, using a
      different DNA-binding protein (TraR), we show that the regulatory output is not a
      particular feature of the specific DNA-binding protein used for the enhancer but
      a general property of synthetic bacterial enhancers.

PMID- 21729784
TI  - YY1 tethers Xist RNA to the inactive X nucleation center.
AB  - The long noncoding Xist RNA inactivates one X chromosome in the female mammal.
      Current models posit that Xist induces silencing as it spreads along X and
      recruits Polycomb complexes. However, the mechanisms for Xist loading and
      spreading are currently unknown. Here, we define the nucleation center for Xist
      RNA and show that YY1 docks Xist particles onto the X chromosome. YY1 is a
      "bivalent" protein, capable of binding both RNA and DNA through different
      sequence motifs. Xist's exclusive attachment to the inactive X is determined by
      an epigenetically regulated trio of YY1 sites as well as allelic origin. Specific
      YY1-to-RNA and YY1-to-DNA contacts are required to load Xist particles onto X.
      YY1 interacts with Xist RNA through Repeat C. We propose that YY1 acts as adaptor
      between regulatory RNA and chromatin targets.

PMID- 21729785
TI  - Stepwise insertion and inversion of a type II signal anchor sequence in the
      ribosome-Sec61 translocon complex.
AB  - In eukaryotic cells, the ribosome-Sec61 translocon complex (RTC) establishes
      membrane protein topology by cotranslationally partitioning nascent polypeptides
      into the cytosol, ER lumen, and lipid bilayer. Using photocrosslinking,
      collisional quenching, cysteine accessibility, and protease protection, we show
      that a canonical type II signal anchor (SA) acquires its topology through four
      tightly coupled and mechanistically distinct steps: (1) head-first insertion into
      Sec61alpha, (2) nascent chain accumulation within the RTC, (3) inversion from
      type I to type II topology, and (4) stable translocation of C-terminal flanking
      residues. Progression through each stage is induced by incremental increases in
      chain length and involves abrupt changes in the molecular environment of the SA.
      Importantly, type II SA inversion deviates from a type I SA at an unstable
      intermediate whose topology is controlled by dynamic interactions between the
      ribosome and translocon. Thus, the RTC coordinates SA topogenesis within a
      protected environment via sequential energetic transitions of the TM segment.

PMID- 21729786
TI  - Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors
      tumor invasion and metastasis.
AB  - Mechanotransduction is a key determinant of tissue homeostasis and tumor
      progression. It is driven by intercellular adhesions, cell contractility, and
      forces generated within the microenvironment and is dependent on extracellular
      matrix composition, organization, and compliance. We show that caveolin-1 (Cav1)
      favors cell elongation in three-dimensional cultures and promotes Rho- and force
      dependent contraction, matrix alignment, and microenvironment stiffening through
      regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1
      fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal
      tissue architecture. Stroma associated with human carcinomas and melanoma
      metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts
      (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1
      depletion in CAFs decreases CAF contractility. Consistently, fibroblast
      expression of Cav1, through p190RhoGAP regulation, favors directional migration
      and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri
      and intratumoral microenvironments to facilitate tumor invasion, correlating
      with increased metastatic potency. Thus, Cav1 modulates tissue responses through
      force-dependent architectural regulation of the microenvironment.

PMID- 21729787
TI  - Assembly of lamina-specific neuronal connections by slit bound to type IV
      collagen.
AB  - The mechanisms that generate specific neuronal connections in the brain are under
      intense investigation. In zebrafish, retinal ganglion cells project their axons
      into at least six layers within the neuropil of the midbrain tectum. Each axon
      elaborates a single, planar arbor in one of the target layers and forms synapses
      onto the dendrites of tectal neurons. We show that the laminar specificity of
      retinotectal connections does not depend on self-sorting interactions among RGC
      axons. Rather, tectum-derived Slit1, signaling through axonal Robo2, guides
      neurites to their target layer. Genetic and biochemical studies indicate that
      Slit binds to Dragnet (Col4a5), a type IV Collagen, which forms the basement
      membrane on the surface of the tectum. We further show that radial glial endfeet
      are required for the basement-membrane anchoring of Slit. We propose that Slit1
      signaling, perhaps in the form of a superficial-to-deep gradient, presents
      laminar positional cues to ingrowing retinal axons.

PMID- 21729788
TI  - SnapShot: spinal cord development.

PMID- 21729790
TI  - Vertebral artery origin stenosis and its treatment.
AB  - Vertebral artery origin stenosis (VAOS) is a common but underappreciated cause of
      stroke. It causes as many as 20% of posterior circulation stroke. This article
      reviews the epidemiology, natural history, and treatment of this condition. We
      focus on the emerging therapeutic endovascular options and their safety and
      durability. Finally, we discuss the gaps in the current understanding of VAOS and
      how best to explore them in the future.

PMID- 21729791
TI  - Issues and answers in pediatric and adolescent gynecology.

PMID- 21729792
TI  - Written emotional disclosure of trauma and trauma history alter pain sensitivity.
AB  - The present study investigated whether written emotional disclosure of trauma and
      trauma history alters sensitivity to experimental pain in healthy women. We
      examined the immediate affective and physiological effects of written emotional
      disclosure and evaluated the pain modulatory effects of this personally relevant
      method of affect induction in women with and without trauma history. Participants
      wrote for 20 minutes about a traumatic or neutral topic prior to the thermal pain
      threshold and the ischemic pain tolerance tests. Written disclosure of trauma
      increased negative affect and skin conductance, which resulted in increased pain
      sensitivity on heat threshold tests. Trauma history was associated with lower
      basal ischemic pain tolerance under the neutral writing condition; however, this
      effect was reversed by disclosure of trauma, suggesting that preexisting
      differences in pain sensitivity and pain modulation may be related to lifetime
      history of trauma. PERSPECTIVE: These findings indicate that written emotional
      disclosure provides an effective method for inducing personally relevant affect
      that is sufficient to modulate pain. History of trauma was related to reduced
      pain tolerance and enhanced stress-induced hypoalgesia, which underscores the
      need for further research to examine the extent to which prior history of trauma
      alters pain processing.

PMID- 21729793
TI  - Evaluation of leukemia inhibitory factor (LIF) in a rat model of postoperative
      pain.
AB  - Postoperative pain remains a significant problem despite optimal treatment with
      current pharmaceutical agents. In an effort to provide better postoperative pain
      control, there is a need to understand the factors that contribute to the
      development of pain after surgery. Leukemia inhibitory factor (LIF) is a
      pleiotropic cytokine released from tissues after injury. We hypothesized that LIF
      expression in skin, muscle, and dorsal root ganglion (DRG) would increase after
      plantar incision. The mRNA and protein expression of LIF and LIF receptor (LIF-R)
      were measured after plantar incision in the rat. Pain behaviors,
      immunohistochemistry, and C-fiber heat responses to LIF were also studied. LIF
      expression increased after incision in skin and muscle, and LIF-R was present in
      large and small DRG neurons. LIF administration to the hindpaw increased pain
      behaviors, a process that was reversed by anti-LIF. However, LIF and anti-LIF
      treatment at the time of incision did not augment or ameliorate pain behaviors.
      LIF treatment activated the second messenger system, JAK-STAT3, in cultured DRG
      neurons, but failed to alter spontaneous activity or heat responses in C-fiber
      nociceptors. In conclusion, LIF is not a target for postoperative analgesia; LIF
      may be important for skin and muscle repair and regeneration after incision.
      PERSPECTIVE: This article highlights an incision pain model for the study of
      factors involved in nociception. The study demonstrates that LIF in is an
      unlikely target for novel early postoperative analgesics.

PMID- 21729794
TI  - A challenge to integrity in spine publications: years of living dangerously with
      the promotion of bone growth factors.

PMID- 21729795
TI  - Physican-directed (off-label) use of recombinant bone morphogenic protein-2: let
      us do it well!

PMID- 21729789
TI  - Design of the stenting and aggressive medical management for preventing recurrent
      stroke in intracranial stenosis trial.
AB  - BACKGROUND: Patients with recent transient ischemic attack (TIA) or stroke caused
      by 70% to 99% stenosis of a major intracranial artery are at high risk of
      recurrent stroke on usual medical management, suggesting the need for alternative
      therapies for this disease. METHODS: The Stenting and Aggressive Medical
      Management for Preventing Recurrent stroke in Intracranial Stenosis trial is an
      ongoing, randomized, multicenter, 2-arm trial that will determine whether
      intracranial angioplasty and stenting adds benefit to aggressive medical
      management alone for preventing the primary endpoint (any stroke or death within
      30 days after enrollment or after any revascularization procedure of the
      qualifying lesion during follow-up, or stroke in the territory of the symptomatic
      intracranial artery beyond 30 days) during a mean follow-up of 2 years in
      patients with recent TIA or stroke caused by 70% to 99% stenosis of a major
      intracranial artery. Aggressive medical management in both arms consists of
      aspirin 325 mg per day, clopidogrel 75 mg per day for 90 days after enrollment,
      intensive risk factor management primarily targeting systolic blood pressure <140
      mm Hg (<130 mm Hg in diabetics) and low density cholesterol <70 mg/dL, and a
      lifestyle modification program. The sample size required to detect a 35%
      reduction in the rate of the primary endpoint from angioplasty and stenting based
      on the log-rank test with an alpha of 0.05, 80% power, and adjusting for a 2%
      loss to follow-up and 5% crossover from the medical to the stenting arm is 382
      patients per group. RESULTS: Enrollment began in November 2008 and 451 patients
      have been enrolled as of March 31, 2011. CONCLUSIONS: This is the first
      randomized stroke prevention trial to compare angioplasty and stenting with
      medical therapy in patients with intracranial arterial stenosis and to
      incorporate intensive management of multiple risk factors and a lifestyle
      modification program in the study design. Hopefully, the results of the trial
      will lead to more effective therapy for this high-risk disease.

PMID- 21729796
TI  - A critical review of recombinant human bone morphogenetic protein-2 trials in
      spinal surgery: emerging safety concerns and lessons learned.
AB  - BACKGROUND CONTEXT: Increasingly, reports of frequent and occasionally
      catastrophic complications associated with use of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) in spinal fusion surgeries are being published.
      In the original peer review, industry-sponsored publications describing the use
      of rhBMP-2 in spinal fusion, adverse events of these types and frequency were
      either not reported at all or not reported to be associated with rhBMP-2 use.
      Some authors and investigators have suggested that these discrepancies were
      related to inadequate peer review and editorial oversight. PURPOSE: To compare
      the conclusions regarding the safety and related efficacy published in the
      original rhBMP-2 industry-sponsored trials with subsequently available Food and
      Drug Administration (FDA) data summaries, follow-up publications, and
      administrative and organizational databases. STUDY DESIGN: Systematic review.
      METHODS: Results and conclusions from original industry-sponsored rhBMP-2
      publications regarding safety and related efficacy were compared with available
      FDA data summaries, follow-up publications, and administrative and organizational
      database analyses. RESULTS: There were 13 original industry-sponsored rhBMP-2
      publications regarding safety and efficacy, including reports and analyses of 780
      patients receiving rhBMP-2 within prospective controlled study protocols. No
      rhBMP-2-associated adverse events (0%) were reported in any of these studies (99%
      confidence interval of adverse event rate <0.5%). The study designs of the
      industry-sponsored rhBMP-2 trials for use in posterolateral fusions and posterior
      lateral interbody fusion were found to have potential methodological bias against
      the control group. The reported morbidity of iliac crest donor site pain was also
      found to have serious potential design bias. Comparative review of FDA documents
      and subsequent publications revealed originally unpublished adverse events and
      internal inconsistencies. From this review, we suggest an estimate of adverse
      events associated with rhBMP-2 use in spine fusion ranging from 10% to 50%
      depending on approach. Anterior cervical fusion with rhBMP-2 has an estimated 40%
      greater risk of adverse events with rhBMP-2 in the early postoperative period,
      including life-threatening events. After anterior interbody lumbar fusion rates
      of implant displacement, subsidence, infection, urogenital events, and retrograde
      ejaculation were higher after using rhBMP-2 than controls. Posterior lumbar
      interbody fusion use was associated with radiculitis, ectopic bone formation,
      osteolysis, and poorer global outcomes. In posterolateral fusions, the risk of
      adverse effects associated with rhBMP-2 use was equivalent to or greater than
      that of iliac crest bone graft harvesting, and 15% to 20% of subjects reported
      early back pain and leg pain adverse events; higher doses of rhBMP-2 were also
      associated with a greater apparent risk of new malignancy. CONCLUSIONS: Level I
      and Level II evidence from original FDA summaries, original published data, and
      subsequent studies suggest possible study design bias in the original trials, as
      well as a clear increased risk of complications and adverse events to patients
      receiving rhBMP-2 in spinal fusion. This risk of adverse events associated with
      rhBMP-2 is 10 to 50 times the original estimates reported in the industry
      sponsored peer-reviewed publications.

PMID- 21729797
TI  - Resetting standards for sponsored research: do conflicts influence results?

PMID- 21729798
TI  - Folly of FDA-approval studies for bone morphogenetic protein.

PMID- 21729799
TI  - Bone morphogenetic protein-2 and spinal arthrodesis: the basic science
      perspective on protein interaction with the nervous system.
AB  - The use and "off-label" indications for recombinant human bone morphogenetic
      protein-2 (rhBMP-2) in spinal arthrodesis have been significantly expanded over
      the last decade. New surgical approaches and pathologies treated often place the
      exogenous protein near the spinal cord or peripheral nerves, yet little data
      exist to the potential interaction between rhBMP-2 and the nervous system. The
      current review was undertaken to provide a basic science perspective on the wide
      ranging effects that rhBMP-2, a potent growth factor, has on the injured spinal
      cord and the local dorsal root ganglia (DRG). Results from the early animal
      studies on neural safety of rhBMP-2 were compared with the more recent in vivo
      work characterizing protein impact on the injured spinal cord. Potential
      mechanism of the rhBMP-2-induced radiculitis after lumbar arthrodesis is also
      discussed. The original pre-FDA approval animal study did not uncover any
      interaction between rhBMP-2 and the spinal cord or the nerve rootlets comprising
      the cauda equina. Recent in vivo work indicated, however, that in a penetrating
      injury model, rhBMP-2 triggers direct signaling in all spinal cord cells. In the
      rat, this interaction was deleterious to spontaneous recovery by exacerbating the
      inflammatory response to injury, increasing the glial scar, and making it more
      inhibitory to axonal regeneration. With respect to posterolateral lumbar
      arthrodesis in a noninjury model, rhBMP-2 use contributed to a transient
      postoperative mechanical hyperalgesia. Potential mechanism of this allodynia is
      through an observed inflammatory response within and around the local DRG. In
      summary, contrary to the original beliefs in the clinical community, rhBMP-2 does
      elicit a profound signaling response within the spinal cord and the peripheral
      ganglia. Recent preclinical studies indicate that rhBMP-2, if provided direct
      access to the spinal cord parenchyma or the DRG, can trigger significant
      inflammation and morphologic changes within these tissues that could be
      deleterious to neurologic recovery.

PMID- 21729800
TI  - Important considerations on bone morphogenetic protein-2 and neuroinflammation.

PMID- 21729801
TI  - Adjacent vertebral body osteolysis with bone morphogenetic protein use in
      transforaminal lumbar interbody fusion.
AB  - BACKGROUND CONTEXT: Recent studies have demonstrated cases of adjacent vertebral
      body osteolysis when assessing the effect of bone morphogenetic protein (BMP) on
      fusion rates. However, no study to date has evaluated the course of osteolysis at
      different periods. PURPOSE: To determine the incidence and resolution of
      osteolysis associated with BMP used in transforaminal lumbar interbody fusions
      (TLIF). STUDY DESIGN: Retrospective review. PATIENT SAMPLE: All TLIF cases using
      BMP performed at one institution with routine postoperative computed tomography
      (CT) scans at defined intervals. OUTCOME MEASURES: Area of osteolysis and fusion
      as determined by CT scan. METHODS: We performed a retrospective analysis of all
      patients at our facility who underwent TLIF with BMP. Included were all patients
      who had obtained a CT scan within 48 hours of surgery, 3 to 6 months
      postoperatively, and 1 to 2 years postoperatively. Areas of osteolysis were
      defined as lucency within the vertebral body communicating with the interbody
      spacer that was not present on the immediately postoperative CT scan. Areas of
      osteolysis were measured in all three planes and the volume used for comparison
      of the 3 to 6 months CT scans with the greater than 1 year CT scan. RESULTS:
      Twenty-three patients who underwent TLIF with BMP had obtained CT scans at all
      time periods required for evaluation. Seventy-eight vertebral bodies/end plates
      were assessed for osteolysis (39 levels). The incidence of osteolysis 3 to 6
      months postoperatively in the adjacent vertebral bodies was 54% compared with 41%
      at 1 to 2 years. The mean volume of osteolysis was at 0.216 cm(3) at 1 to 2 years
      compared with 0.306 cm(3) at 3 to 6 months (p=.082). The area/rate of osteolysis
      did not appear to significantly affect the rate of fusion or final outcome with
      an overall union rate of 83%. CONCLUSIONS: The rate of osteolysis decreased at 1
      year compared with 3 to 6 months, but only 24% of the vertebral bodies with
      evidence of osteolysis at 3 to 6 months completely resolved by 1 year.

PMID- 21729802
TI  - Iliac crest bone graft: are the complications overrated?

PMID- 21729803
TI  - Local bone graft harvesting and volumes in posterolateral lumbar fusion: a
      technical report.
AB  - BACKGROUND CONTEXT: In lumbar surgery, local bone graft is often harvested and
      used in posterolateral fusion procedures. The volume of local bone graft
      available for posterolateral fusion has not been determined in North American
      patients. Some authors have described this as minimal, but others have suggested
      the volume was sufficient to be reliably used as a stand-alone bone graft
      substitute for single-level fusion. PURPOSE: To describe the technique used and
      determine the volume of local bone graft available in a cohort of patients
      undergoing single-level primary posterolateral fusion by the authors harvesting
      technique. STUDY DESIGN: Technical description and cohort report. PATIENT SAMPLE:
      Consecutive patients undergoing lumbar posterolateral fusion with or without
      instrumentation for degenerative processes. OUTCOME MEASURE: Local bone graft
      volume. METHODS: Consecutive patients undergoing lumbar posterolateral fusion
      with or without instrumentation for degenerative processes of were studied. Local
      bone graft was harvested by a standard method in each patient and the volume
      measured by a standard procedure. RESULTS: Twenty-five patients were studied, and
      of these 11 (44%) had a previous decompression. The mean volume of local bone
      graft harvested was measured to be 25 cc (range, 12-36 cc). Local bone graft was
      augmented by iliac crest bone in six of 25 patients (24%) if the posterolateral
      fusion bed was not well packed with local bone alone. There was a trend to
      greater local bone graft volumes in men and in patients without previous
      decompression. CONCLUSION: Large volumes of local bone can be harvested during
      posterolateral lumbar fusion surgery. Even in patients with previous
      decompression the volume harvested is similar to that reported harvested from the
      posterior iliac crest for single-level fusion.

PMID- 21729804
TI  - Gene therapy for spinal fusion.

PMID- 21729805
TI  - Bone morphogenetic protein-binding peptide reduces the inflammatory response to
      recombinant human bone morphogenetic protein-2 and recombinant human bone
      morphogenetic protein-7 in a rodent model of soft-tissue inflammation.
AB  - BACKGROUND CONTEXT: Bone morphogenetic protein (BMP)-2 and BMP-7 are used to
      enhance bone formation in spine surgery, but the use of these materials is
      associated with side effects including inflammation, especially in the soft
      tissues of the neck. Bone morphogenetic protein-binding peptide (BBP) binds BMP-2
      and BMP-7 and imparts a "slow-release" property to collagen carrier. PURPOSE: To
      test the hypothesis that the addition of BBP will reduce the soft-tissue
      inflammation induced by the implantation of BMP-2 and BMP-7 on a collagen sponge.
      STUDY DESIGN/SETTING: Prospective in vivo rodent model of inflammation. METHODS:
      We implanted six different materials absorbed onto collagen sponges: absorbable
      collagen sponge (ACS) alone; BBP alone; recombinant human bone morphogenetic
      protein (rhBMP)-2 alone; rhBMP-2 plus BBP; rhBMP-7 alone; and rhBMP-7 plus BBP.
      Sponges were implanted bilaterally (subcutaneously [SC] and intramuscularly [IM])
      into the backs of rats. Using magnetic resonance imaging, inflammation was
      assessed in terms of soft-tissue edema volume at 3 hours and at 2, 4, and 7 days.
      The animal subjects were killed on Day 7, and the dimensions of the inflammatory
      mass were measured manually in the case of SC tissue and those of the
      inflammatory zone were determined subsequently by microscopic examination in the
      case of muscle. RESULTS: Both the SC and the IM soft-tissue edema volumes in the
      rhBMP-2 plus BBP and the rhBMP-7 plus BBP groups were significantly lower than
      those observed in the rhBMP-2 alone and rhBMP-7 alone groups. The edema volume
      associated with BBP alone was greater than that associated with ACS alone but
      less than that associated with the other treatment groups. The measurements of
      inflammatory masses and zone yielded similar results. CONCLUSIONS: Bone
      morphogenetic protein-binding peptide may reduce the inflammatory response
      associated with the use of rhBMP-2 and rhBMP-7 in a rodent model of inflammation
      and in a form that has previously been shown to enhance the activity of BMPs.
      These preliminary studies suggest that BBP may have the potential to be used in
      the future to improve healing and reduce soft-tissue swelling in surgical
      applications of BMPs.

PMID- 21729806
TI  - Vertebral body osteolysis after minimal-access transforaminal interbody fusion.

PMID- 21729807
TI  - Functional hemodynamic parameters: is prediction of fluid responsiveness reliable
      or not?

PMID- 21729808
TI  - Do nondiabetic patients undergoing coronary artery bypass grafting surgery
      require intraoperative management of hyperglycemia?
AB  - OBJECTIVE: To study the effect of blood glucose (BG) control with insulin in
      preventing hyperglycemia during and after coronary artery bypass grafting (CABG)
      surgery in nondiabetic patients. METHODS: In a randomized clinical trial, 120
      nondiabetic patients who underwent elective CABG surgery were enrolled for study
      of whether the control of hyperglycemia was a need in such a surgery in a
      teaching heart hospital. The patients were randomly divided into study (n=60) and
      control (n=60) groups. In the study group, insulin was infused to maintain BG
      level between 110 mg/dL and 126 mg/dL (a modified insulin therapy protocol, and
      in the control group, the patients were excepted). Insulin therapy was limited to
      intraoperative period. BG levels during surgery and up to 48 hours after surgery
      and early postoperative complications were compared between the study and control
      groups. RESULTS: One hundred seventeen patients completed the study (59 patients
      in study group and 58 in control group). Peak intraoperative BG level in the
      study group was 126.4+/-17.9 mg/dL and in the control group was 137.3+/-17.6
      mg/dL (p=0.024). The frequencies of severe hyperglycemia (BG>=180 mg/dL) were 6
      of 59 (10.1%) in the study group and 19 of 58 (32.7%) in the control group during
      operation (p=0.002). Peak postoperative BG level in the study group was 194.8+/
      41.2 mg/dL and was 199.8+/-43.2 mg/dL in the control group (p=0.571). There was
      no hypoglycemic event in either group. The frequencies of early postoperative
      complications were 10 of 59 (16.9%) in the study group and 19 of 58 (32.7%) in
      the control group (p=0.047). CONCLUSIONS: Hyperglycemia (BG>=126 mg/dL) is common
      in nondiabetic patients undergoing CABG surgery. A modified insulin therapy to
      maintain BG level between 110 mg/dL and 126 mg/dL may be acceptable for avoiding
      hypoglycemia and keeping intraoperative BG levels in acceptable range in
      nondiabetics.

PMID- 21729809
TI  - Increased oxidative stress and gut ischemia caused by prolonged pneumoperitoneum
      in patients undergoing robot-assisted laparoscopic radical prostatectomy.
AB  - OBJECTIVE: To investigate changes in plasma oxidative stress markers associated
      with prolonged pneumoperitoneum during robot-assisted laparoscopic radical
      prostatectomy (RALP). METHODS: In all, patients of ASA Physical Status II-III who
      intended to undergo RALP were enrolled in the study. Arterial plasma levels of
      malondialdehyde (MDA) and intramucosal pH were measured 1 minute before and at 1
      hour, 2 hours, 3 hours, and 4 hours after the introduction of pneumoperitoneum at
      an insufflation pressure of 15 mmHg; likewise, they were again measured every 10
      minutes after deflation for 60 minutes, at 2 hours and 12 hours after deflation.
      RESULTS: The mean duration of pneumoperitoneum was around 4 hours. After
      induction of pneumoperitoneum, the MDA concentrations were significantly elevated
      at various time points as compared with the preinsufflation value. Significant
      increase of MDA value was noted also 30 minutes after deflation as compared with
      the pre-deflation levels. The intramucosal pH value decreased significantly after
      CO(2) insufflation compared with the preinsufflation values. It also increased
      significantly 2 hours after CO(2) deflation as compared with the pre-deflation
      values. CONCLUSION: A prolonged pneumoperitoneum in RALP results in decreased
      splanchnic blood flow. Pneumoperitoneum itself produces oxidative stress, and
      ischemia-reperfusion model after deflation of pneumoperitoneum produces more
      oxidative stress.

PMID- 21729810
TI  - Intraoperative blood and fluid administration differences in primary liver
      transplantation versus liver retransplantation.
AB  - OBJECTIVES: Liver retransplantation (Re-LT) is the effective therapy for
      irreversible liver graft failure after primary liver transplantation (LT). The
      challenges faced by the operative team in the Re-LT setting have been seldom
      elucidated. Our aim is to analyze the differences in fluid management in primary
      LT and Re-LT during the surgical procedure. METHODS: The anesthesia charts of 16
      patients who underwent both primary LT and Re-LT at our center in the space from
      October 1995 to May 2009 were analyzed. Group 1 (GI) consisted of patients who
      underwent primary LT, whereas patients in Group 2 (GII) were patients in GI but
      underwent Re-LT. GI was further divided into two subgroups depending on whether
      they had previous abdominal surgery before primary LT (GIB) or not (GIA).
      Wilcoxon signed-ranks test was used to compare GI and GII, and GIA and GIB. A p
      value less than 0.05 was regarded as significant. Data were given as mean +/-
      standard deviation. RESULTS: Blood loss was significantly increased from 48.9 +/-
      106 mL/kg in GI to 251.5 +/- 242 mL/kg in GII. Consequently more blood products,
      crystalloids, sodium bicarbonate, calcium chloride, and neosynephrine were
      required to support the hemodynamics in GII. In GI, GIB tended to bleed more and
      required more blood transfusions than GIA. CONCLUSION: More bleeding is expected
      in Re-LT than primary LT. Additional anesthetic personnel, more intravenous
      lines, and blood and blood products should be readily available to deal with the
      emergent fluid and hemodynamic resuscitations in anesthesia for Re-LT.

PMID- 21729811
TI  - The effect of combined ephedrine and lidocaine pretreatment on pain and
      hemodynamic changes due to propofol injection.
AB  - OBJECTIVES: Injection pain and hypotension are two main adverse effects of
      propofol that discourage uniform acceptation. The aim of this study was to
      compare the effect of ephedrine-lidocaine combination with lidocaine and
      ephedrine alone on injection pain and hemodynamic changes caused by propofol
      injection. METHODS: One hundred and sixty five patients were randomly allocated
      to five groups to receive either lidocaine 0.5 mg/kg (Group L) alone, ephedrine
      30 MUg/kg (Group E30) alone, ephedrine 70 MUg/kg (Group E70) alone, lidocaine 0.5
      mg/kg-ephedrine 30 MUg/kg Group LE, or 2 mL saline (Group S). One minute after
      the respective study solution was given propofol 2 mg/kg was injected. Face pain
      scale and verbal rating scale were then evaluated. The mean arterial blood
      pressure (MAP) and heart rate (HR) were recorded before injection of the test
      solution, just before the intubation, and 1 minute after intubation. RESULTS:
      Patients in the Group L and Group LE showed significantly smaller pain scores
      compared with the saline group (Group S) [95% confidence interval (CI) 0.50-1.50;
      p = 0.003 and 95% CI 1.000-1.500; p = 0.004, respectively). The pain scores in
      Group E30 and Group E70 failed to show a significant difference with that of the
      Group S (p = 0.193 and p = 0.184, respectively). The changes of MAP before and
      after propofol injection between the Group L versus Group E30, Group E70, and
      Group LE were found to be significant (95% CI 5.27-14.49; p = 0.000), (95% CI
      4.72-16.39; p = 0.001), and (95% CI 5.94-16.47; p = 0.001), respectively. The HR
      changes, before and after propofol injection, tended to be smaller in ephedrine
      groups than in Group L and Group S (p < 0.05). CONCLUSION: Pretreatment with
      combination of small-dose ephedrine and lidocaine could reduce the incidence and
      intensity of propofol-induced pain and also result in more stable hemodynamic
      profile, but however, the combination of two drugs failed to work better in
      further reduction of pain.

PMID- 21729812
TI  - Monitoring fluid responsiveness.
AB  - Functional hemodynamic parameters, such as stroke volume variation (SVV) and
      pulse pressure variation (PPV), are useful hemodynamic monitoring tools for the
      assessment of fluid responsiveness. These parameters are based on heart-lung
      interaction during positive mechanical pressure ventilation: Cyclic changes of
      intrathoracic pressure result in a reduced venous return and a decreased cardiac
      stroke volume after inspiration followed by a restoration of preload and stroke
      volume after expiration. Hemodynamic monitoring systems based on pulse wave
      analysis allow an automatic assessment of SVV and--at least for some of the
      devices--of PPV. Moreover, PPV is being integrated in the standard monitoring in
      the operating room and the intensive care unit, and the noninvasive
      plethysmographic assessment of fluid responsiveness has been recently introduced.
      These developments will result in a broader application of functional hemodynamic
      parameters in the near future. In contrast to traditional preload parameters
      (i.e. central venous pressure), SVV and PPV allow the prediction of fluid
      responsiveness and thus the determination of the actual position on an individual
      Frank-Starling curve or--in other words--the assessment of an individual preload
      reserve. Different studies in the last decade were able to prove the validity of
      this concept. However, to use these functional hemodynamic parameters in daily
      clinical practice, some limitations have to be considered. Arrhythmia and right
      heart failure, but also spontaneous breathing of a patient, or small tidal
      volumes may preclude reliable assessment. Based on these aspects, an ideal area
      of application of these parameters may be the use during perioperative
      hemodynamic optimization to improve patient outcome. However, only few studies on
      goal-directed therapy guided by these parameters have been published so far.

PMID- 21729813
TI  - Modified lightwand intubation in a child with spondyloepiphyseal dysplasia
      congenita.
AB  - This is the case report on a 1-year 9-month-old boy suffering from
      spondyloepiphyseal dysplasia congenita who was successfully intubated with our
      modified lightwand intubation procedure for general anesthesia to undergo
      bilateral herniorrhaphy despite the great likelihood of facing a difficult airway
      because of unstable cervical spine. We bent the pediatric wand after it was
      encased in an endotracheal (ET) tube of appropriate diameter. The light tip of
      the wand was let to protrude just out of the bevel of the ET tube. Once the light
      bulb properly transilluminated the trachea, the ET tube was threaded gently into
      the trachea. The patient recovered from anesthesia smoothly and was discharged on
      the next day. This maneuver can facilitate both visual and tactile confirmations
      of the position and proper tube size. The effectiveness and safety of our
      modified lightwand intubation procedure is well demonstrated.

PMID- 21729814
TI  - Cardiovascular collapse after labetalol for hypertensive crisis in an undiagnosed
      pheochromocytoma during cesarean section.
AB  - Pheochromocytoma is a catecholamine-producing tumor but rarely delayingly
      diagnosed until during pregnancy. We reported a pregnant woman who underwent
      emergent cesarean section because of intrauterine growth retardation,
      oligohydramnios, and hypertension. The existence of an undiagnosed
      pheochromocytoma was suspected by the unusual hemodynamic response to spinal
      anesthesia, abdominal compressions, and operative stimulus. Hypertensive crisis
      occurred during the operation and she was sent to the intensive care unit for
      postoperative care. In the intensive care unit, cardiovascular collapse occurred
      after nonselective beta-adrenergic blockade. Unexpected hypertensive crisis
      during the perioperative period should alert clinicians to the possibility of a
      pheochromocytoma. For the treatment of choice, nonselective beta-adrenergic
      blockade should not be used before the alpha-blockade.

PMID- 21729815
TI  - Successful reversal of bupivacaine and lidocaine-induced severe junctional
      bradycardia by lipid emulsion following infraclavicular brachial plexus block in
      a uremic patient.
AB  - Cardiac toxicity of bupivacaine has long been documented and it could be
      potentiated in certain circumstances, such as preexisting cardiac conduction
      abnormality or uremic status. The concept that lipid emulsion acts as a rescue of
      bupivacaine's toxicity has prevailed pending universal recognition. Herein, we
      report the successful use of lipid to resuscitate a female uremic patient who
      sustained junctional bradycardia while she was receiving ultrasound-guided
      infraclavicular brachial plexus block with the dose of local anesthetics far
      below the currently recommended maximum one. The possible mechanisms for the
      occurrence of cardiotoxicity in this case are discussed and the role of lipid
      emulsion as a treatment is reviewed.

PMID- 21729816
TI  - Bacterial infection in deep paraspinal muscles in a parturient following epidural
      analgesia.
AB  - We report a case of paraspinal muscle infection shortly after epidural analgesia
      for labor pain in a nulliparous parturient who was subjected to emergent Cesarean
      section because of fetal distress. Epidural morphine was administered for 3 days
      for postoperative pain control. She began to have constant lower back pain on
      postpartum Day 4. Magnetic resonance image study revealed a broad area of
      subcutaneous edema with a continuum along the catheter trajectory deep to the
      paraspinal muscles. An injection-related bacterial infection was suspected; the
      patient was treated with intravenous antibiotics and was soon cured
      uncomplicatedly. Epidural analgesia is effective to control labor pain and, in
      general, it is safe. However, the sequelae of complicated infection may be
      underestimated. We herein report a case complicated by iatrogenic infection,
      discuss the causes, and give suggestions for prevention.

PMID- 21729817
TI  - Emergency cesarean delivery for fetal distress--a three-pronged approach.

PMID- 21729818
TI  - Intervention study to improve smoking cessation during hospitalization.
AB  - OBJECTIVES: In France, hospitals have been smoke free since February 2007. A
      period of hospitalization may be a good time to enhance a smoker's motivation to
      quit. This study aimed to assess whether training medical staff in smoking
      cessation management might improve the rate of smoking cessation during
      hospitalization. STUDY DESIGN: Non-randomized intervention study. METHODS: Staff
      of the participating care units either received (intervention group) or did not
      receive (control group) training in smoking cessation management. The dependent
      variable was the proportion of inpatients that continued to smoke before (Period
      1) and after (Period 2) the training session. RESULTS: In total, 358 patients
      were included. In Period 1, 55.6% and 50% of the smokers from the intervention
      and control groups stopped smoking, respectively; the corresponding rates in
      Period 2 were 64.3% and 48.1%. In Period 2, 36.4% and 31.8% of the smokers from
      the intervention and control groups claimed that they had received motivational
      counselling. In the intervention group, the request rate for nicotine replacement
      therapy (NRT) was higher (41.7%) compared with the control group (11.1%). In both
      groups, patients asked for NRT more often (P < 0.001) when they had received
      motivational counselling. CONCLUSIONS: This study was not able to demonstrate
      that training medical staff in smoking cessation management has a significant
      impact on smoking cessation in hospitalized smokers. The delivery of medium
      intensity support to all smokers appears to be out of reach of physician/nurse
      teams. New strategies are needed, including a team specifically dedicated to the
      problems of addiction.

PMID- 21729819
TI  - External gamma-ray dose rate and radon concentration in indoor environments
      covered with Brazilian granites.
AB  - Health hazard from natural radioactivity in Brazilian granites, covering the
      walls and floor in a typical dwelling room, was assessed by indirect methods to
      predict external gamma-ray dose rates and radon concentrations. The gamma-ray
      dose rate was estimated by a Monte Carlo simulation method and validated by in
      situ measurements with a NaI spectrometer. Activity concentrations of (232)Th,
      (226)Ra, and (40)K in an extensive selection of Brazilian commercial granite
      samples measured by using gamma-ray spectrometry were found to be 4.5-450 Bq kg(
      1), 4.9-160 Bq kg(-1) and 190-2029 Bq kg(-1), respectively. The maximum external
      gamma-ray dose rate from floor and walls covered with the Brazilian granites in
      the typical dwelling room (5.0 m * 4.0 m area, 2.8 m height) was found to be 120
      nGy h(-1), which is comparable with the average worldwide exposure to external
      terrestrial radiation of 80 nGy h(-1) due to natural sources, proposed by United
      Nations Scientific Committee on the Effects of Atomic Radiation. Radon
      concentrations in the room were also estimated by a simple mass balance equation
      and exhalation rates calculated from the measured values of (226)Ra
      concentrations and the material properties. The results showed that the radon
      concentration in the room ventilated adequately (0.5 h(-1)) will be lower than
      100 Bq m(-3), value recommended as a reference level by the World Health
      Organization.

PMID- 21729820
TI  - Healthier before they migrate, less healthy when they return? The health of
      returned migrants in Mexico.
AB  - Over the course of the 20th century, Mexico-U.S. migration has emerged as an
      important facet of both countries, with far reaching economic and social impacts.
      The health of Mexican immigrants in the U.S. has been well studied, but
      relatively less is known about the health of returned migrants to Mexico. The
      objectives of this paper are twofold. Relying on health data pertaining to two
      stages of the life course, early life health (pre-migration) and adult health
      (post-migration) from the Mexican Migration Project gathered between 2007 and
      2009, we aim to assess disparities in adult health status between male returned
      migrants and male non-migrants in Mexico, accounting for their potentially
      different early life health profiles. While we find evidence that returned
      migrants had more favorable early life health, the results for adult health are
      more complex. Returned migrants have a higher prevalence of heart disease,
      emotional/psychiatric disorders, obesity, and smoking than non-migrants but no
      differences are found in self-rated health, diabetes, or hypertension.

PMID- 21729821
TI  - Household and community HIV/AIDS status and child malnutrition in sub-Saharan
      Africa: evidence from the demographic and health surveys.
AB  - This paper examines the extent to which under five children in households or
      communities adversely affected by HIV/AIDS are disadvantaged, in comparison with
      other children in less affected households/communities. The study is based on
      secondary analysis of the Demographic and Health Survey (DHS) data collected
      during 2003-2008 from 18 countries in sub-Saharan Africa, where the DHS has
      included HIV test data for adults of reproductive age. We apply multilevel
      logistic regression models that take into account the effect of contextual
      community/country level HIV/AIDS factors on child malnutrition. The outcome
      variable of interest is child undernutrition: stunting, wasting and underweight.
      The results suggest that across countries in sub-Saharan Africa, children whose
      mothers are infected with HIV are significantly more likely to be stunted, wasted
      or underweight compared to their counterparts of similar demographic and socio
      economic background whose mothers are not infected. However, the nutritional
      status of children who are paternal orphans or in households where other adults
      are HIV positive are not significantly different from non-orphaned children or
      those in households where no adult is infected with HIV. Other adult household
      members being HIV positive is, however, associated with higher malnutrition among
      younger children below the age of one. Further analysis reveals that the effect
      of mothers' HIV status on child nutritional status (underweight) varies
      significantly across communities within countries, the effect being lower in
      communities with generally higher levels of malnutrition. Overall, the findings
      have important implications for policy and programme efforts towards improved
      integration of HIV/AIDS and child nutrition services in affected communities and
      other sub-groups of the population made vulnerable by HIV/AIDS. In particular,
      children whose mothers are infected with HIV deserve special attention.

PMID- 21729822
TI  - Towards emergency management of natural disasters and critical accidents: the
      Greek experience.
AB  - This paper presents the findings of a prototype study which sought to identify
      factors that contribute to effective emergency management in Greece and other
      European states regarding both natural disasters and critical accidents. The
      parameters for proper action and successful intervention in operational and
      logistical are identified based on the document analysis and interviews with
      emergency responders. The interviews are conducted between state-owned and
      voluntary organizations. They were asked to rate in terms of their importance for
      effective emergency response efforts. This paper offers useful information of the
      organization and management of emergency response in Greece, as well as provides
      interesting responders' opinions data concerning important priorities in the
      emergency management area. Despite the fact that the data come from the Greek
      experience, the conclusions may be applied for a broader use in the emergency
      planning of disasters. The whole study has been undertaken within the European
      Pre-Emergencies (PreEm) project.

PMID- 21729823
TI  - Merkel cell carcinoma - a population-based epidemiological study in Finland with
      a clinical series of 181 cases.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignancy of the skin, and its
      incidence is reported to be rising. The purpose of this study was to calculate
      its incidence and survival ratios, and to describe the clinical characteristics
      of Merkel cell carcinoma patients in Finland. METHODS: We calculated the
      incidence of MCC based on data from the Finnish Cancer Registry. In addition,
      patient files from hospitals and primary health care centres were reviewed for
      detailed data on the treatment and disease recurrence of 181 patients diagnosed
      with MCC in Finland during 1983-2004, and relative survival ratios were
      calculated for them. RESULTS: The incidence (per 100,000) of MCC in Finland in
      1989-2008 was 0.11 for men and 0.12 for women, adjusted for age to the world
      standard population. The mean age at diagnosis was 76 years (range 27-100), and
      69% of the patients were women. The most common site of the primary tumour was
      the head and neck (53%). No extra benefit was gained from a wide surgical margin
      (>= 2 cm) compared to a margin of 0.1-0.19 cm, but an intralesional excision was
      more often associated with local recurrence. None of the patients with Stage I-II
      disease who had received postoperative radiotherapy to the tumour bed had a local
      recurrence. The 5-year relative survival ratio amongst men was 36% (95%
      confidence interval 20-54%), and amongst women 69% (56 to -82%). CONCLUSIONS: MCC
      is a rare disease in Finland, with incidence rates similar to those in the other
      Nordic countries. Our results support the view that complete excision with clear
      margins and post operative radiotherapy decrease local recurrences.

PMID- 21729824
TI  - Co-firing of eucalyptus bark and rubberwood sawdust in a swirling fluidized-bed
      combustor using an axial flow swirler.
AB  - Co-combustion of eucalyptus bark (as shredded fuel) and rubberwood sawdust was
      conducted in a swirling fluidized-bed combustor using a 22-vane axial flow
      swirler. During the co-firing tests, the fuel blend feed rate was maintained at
      about 60 kg/h, while the mass/energy fraction of the blended fuels was variable.
      Excess air supply ranged from 20% to 80% for each fuel option via variation of
      primary air, while secondary air was injected tangentially into the bed splash
      zone at a constant flowrate. For comparison, tests with pure rubberwood sawdust
      at similar operating conditions were performed as well. Temperature and
      concentrations of O(2), CO and NO were measured along radial and axial directions
      in the combustor as well as at stack. For all fuel firing options, the radial and
      axial temperature profiles in the reactor were found to be weakly dependent on
      operating conditions. However, the gas concentration profiles exhibited apparent
      effects of fuel properties, excess air and secondary air injection, which
      resulted in variable emission characteristics of the combustor. For the sawdust
      energy fraction in the fuel blend of about 0.85, CO and NO emissions can be
      controlled at acceptable levels (both complying with the national emission
      limits) by maintaining excess air between 50% and 55%. Under such conditions, the
      co-combustion of high-moisture eucalyptus bark and rubberwood sawdust in the
      proposed combustor occurs in a stable regime with high, 99.6%, combustion
      efficiency.

PMID- 21729825
TI  - Applied anatomy of the latissimus dorsi free flap for refinement in one-stage
      facial reanimation.
AB  - BACKGROUND: The face can be reanimated after long-term paralysis by free
      microneurovascular tissue transfer. Flaps from gracilis and pectoralis minor
      usually require a two-stage procedure with a cross-face nerve graft. Latissimus
      dorsi has a much longer muscular nerve, the thoracodorsal nerve, which could
      avoid the need for a second cross-face nerve graft. Our hypothesis is that the
      neurovascular pedicles of small segments of latissimus dorsi would be long enough
      to reach the opposite side of the face and to provide a reliable blood and nerve
      supply to the flaps. METHOD: To test this hypothesis the thoracodorsal pedicle
      and its primary branches were dissected in eleven embalmed cadavers. The
      segmental vessels and nerves were then traced in a series of simulated flaps
      approximately 8-10 cm * 2-3 cm by micro-dissection, tissue clearing and
      histology. RESULTS: The thoracodorsal pedicle is 10-14 cm long to where it enters
      the muscle, and with intra-muscular dissection small chimeric muscle segments 8
      10 cm * 2-3 cm can be raised with a clearly defined neurovascular supply. Using
      micro-dissection the neurovascular pedicle can be lengthened to reach across the
      face. Segmental arteries and nerves extended to the distal end of all the flaps
      examined. Artery, vein and nerve run together and are of substantial diameter.
      CONCLUSION: Small muscle segments of latissimus dorsi can be raised on long
      neurovascular pedicles. The vessels and nerves are substantial and the likelihood
      of surgical complications such as flap necrosis and functional disuse on
      transplantation appear low. Although in our opinion the use of cross-face nerve
      grafts and transfer of smaller muscle flaps remains the gold standard in facial
      reanimation in straightforward cases, the micro-dissected latissimus dorsi flap
      is a useful option in complex cases of facial reanimation. CLINICAL APPLICATION:
      Facial reanimation using micro-dissected segments of latissimus dorsi has been
      performed in four complex cases of facial paralysis.

PMID- 21729827
TI  - "Finally, we may be all wrong... but only time will tell if we were right".

PMID- 21729828
TI  - Virtual bench testing of new generation coronary stents: why would we want to
      publish this paper?

PMID- 21729829
TI  - Should stent selection in diabetic patients be considered as a special case?

PMID- 21729830
TI  - Beyond the lumen border: on the use of intravascular ultrasound in the left main
      coronary artery.

PMID- 21729831
TI  - European interventional cardiology: a global player.

PMID- 21729832
TI  - Clinical and angiographic outcomes of elderly patients treated with everolimus
      eluting versus paclitaxel-eluting stents: three-year results from the SPIRIT III
      randomised trial.
AB  - AIMS: Age is an important determinant of outcomes in patients treated with
      percutaneous coronary intervention (PCI). This report from the randomised
      multicentre SPIRIT III trial compares the outcomes in elderly and younger
      patients treated with everolimus-eluting stent (EES) versus paclitaxel-eluting
      stent (PES). METHODS AND RESULTS: A total of 1,002 patients with stable or
      unstable angina or inducible ischaemia undergoing PCI were randomised in a 2:1
      ratio to receive EES or PES. Outcomes were examined across the randomised groups
      as a function of age and stent type. Patients >=65 years of age (elderly) treated
      with EES vs. PES had lower in-segment late lumen loss (0.11+/-0.32 mm vs. 0.38+/
      0.55 mm, respectively, p=0.0002) and lower rates of binary in-segment restenosis
      (3.4% vs. 15.5%, p = 0.004) at eight months, along with a 48% lower incidence of
      3-year target vessel failure (TVF=cardiac death, myocardial infarction and
      ischaemia-driven target vessel revascularisation [TVR]; 10.8% vs. 20.8%,
      p=0.009), mainly due to a lower incidence of TVR (5.4% vs. 9.2%, p=0.20). Among
      EES patients, elderly compared to younger patients had comparable rates of binary
      in-segment restenosis (3.4% vs. 5.6%, p=0.44) at eight months but paradoxically
      lower rates of TVF (10.8% vs. 17.1%, p=0.03) at three years. Among PES patients,
      elderly compared to younger patients had a higher rate of binary in-segment
      restenosis (15.5% vs. 3.4%, p=0.01) at eight months and no difference in the rate
      of 3-year TVF (20.8% vs. 19.4%, p=0.77) .There was a significant interaction
      between stent assignment, age >=65 years and 8-month angiographic in-segment late
      loss (p=0.001). CONCLUSIONS: Implantation of both EES and PES appeared to be safe
      in elderly patients, however EES compared to PES was more effective due to
      enhanced 3-year MACE- and TVF-free outcomes. Further research should clarify age
      specific mechanisms of neointimal response after treatment with drug-eluting
      stents.

PMID- 21729833
TI  - Two-year clinical outcomes of paclitaxel-eluting stents for in-stent restenosis
      in patients from the ARRIVE programme.
AB  - AIMS: To examine the incidence of clinical events after implantation of the TAXUS
      Express paclitaxel-eluting stent (PES) for in-stent restenosis (ISR) in an
      unselected patient population. Implantation of bare metal stents in native
      coronary vessels can result in ISR rates exceeding 50%. PES significantly reduces
      ISR-lesion restenosis and improves event-free survival versus vascular
      brachytherapy. METHODS AND RESULTS: The 7,492-patient ARRIVE registry enrolled
      patients receiving >=1 TAXUS Express stent at procedure initiation with no
      inclusion/exclusion criteria, including 489 patients with ISR. Endpoints were
      independently adjudicated. All major cardiac events were monitored plus a 10%-20%
      sample per site. ISR patient 2-year follow-up was 94% complete (462/489).
      Compared to simple-use patients undergoing native coronary intervention (N=2698)
      or other, non-ISR expanded-use cases (N=4305), ISR patients had significantly
      more baseline comorbidities/complex disease. They had higher 2-year rates for
      mortality (8.6% vs. 4.2%, P<0.001), myocardial infarction (5.0% vs. 2.2%,
      P<0.001), definite/probable stent thrombosis (4.0% vs. 1.4%, P<0.001), and target
      lesion revascularisation (12.3% vs. 5.4%, P<0.001) versus simple-use. Safety
      outcomes were comparable between the ISR and non-ISR expanded-use subgroups but
      target vessel revascularisation (TVR) was significantly higher for ISR (16.0% vs.
      10.9%, P=0.003). ISR was independently associated with increased risk for TVR
      (1.4-fold). CONCLUSIONS: ARRIVE ISR, one of the largest studied cohorts of
      patients receiving DES for ISR, had higher risk for clinical events versus simple
      use patients but comparable safety outcomes versus other expanded-use patients
      except for significantly higher revascularisation. ARRIVE provides a detailed
      estimate of 2-year outcomes in these real-world patients.

PMID- 21729834
TI  - Late lumen loss and intima hyperplasia after sirolimus-eluting and zotarolimus
      eluting stent implantation in diabetic patients: the diabetes and drug-eluting
      stent (DiabeDES III) angiography and intravascular ultrasound trial.
AB  - AIMS: Patients with diabetes mellitus have increased risk of in-stent restenosis
      after coronary stent implantation due to neointimal hyperplasia (NIH). The aim of
      this study was to use quantitative coronary angiography (QCA) and volumetric
      intravascular ultrasound (IVUS) to evaluate the effects of the sirolimus-eluting
      Cypher(r) stent (SES) and the zotarolimus-eluting Endeavor(r) stent (ZES) on
      angiographic late lumen loss and intima hyperplasia in diabetic patients. METHODS
      AND RESULTS: In the DiabeDES III trial, 127 patients were randomised to SES or
      ZES stent implantation. Angiographic 10-month follow-up data were available in
      105 patients, including 48 SES and 57 ZES treated patients. Angiographic
      endpoints were in-stent late lumen loss and minimal lumen diameter. IVUS
      endpoints included NIH volume and in-stent percent volume obstruction. Baseline
      clinical characteristics and lesion parameters were similar in the two groups. At
      10-month follow-up, angiographic in-stent late lumen loss (0.14+/-0.37 mm vs.
      0.74+/-0.45 mm, p<0.001) was reduced and minimum lumen diameter was higher
      (2.36+/-0.53 mm vs. 1.96+/-0.65, p<0.001) in the SES group as compared to the ZES
      group. As compared to the ZES group, NIH volume was significantly reduced in the
      SES group (median [interquartile range]: 0.0 mm3 [0.0 to 1.2] vs. 16.5 mm3 [6.2
      to 31.1], p<0.001). In-stent% volume obstruction was significantly reduced in SES
      as compared to ZES (median [interquartile range]: 0.0% [0.0-0.7] vs. 13.0% [6.7
      20.8], p<0.001). CONCLUSIONS: In diabetic patients, the SES reduced angiographic
      late lumen loss and inhibited NIH more effectively than ZES.

PMID- 21729835
TI  - Cost analysis of four major drug-eluting stents in diabetic populations.
AB  - AIM: To use an indirect comparisons approach and conduct a cost analysis
      comparing four drug-eluting stents (DES) from a United States (US) payer (i.e.,
      fixed-fee reimbursement) perspective. METHODS AND RESULTS: Studies were chosen
      that randomised two or more DES in diabetic patients. A one-year target lesion
      revascularisation (TLR) risk for Taxus was first derived. Risk Ratios (RRs) for
      each DES versus Taxus were calculated through meta-analyses. The RRs were
      multiplied by the average TLR risk for Taxus to estimate DES TLR risks. Estimates
      were added to a budget-impact model, along with utilisation and reimbursement
      rates for diagnosis-related groups. Budgets were calculated, assuming 100% stent
      use and 200,000 diabetic beneficiaries. One-year TLR risks were estimated to be
      3.2%, 7.1%, 6.9% and 7.9% for Cypher, Endeavor, Taxus and Xience respectively. By
      substituting Cypher for DES with higher TLR, results predicted annual cost
      savings greater than $146 million per population ($ 733 per patient). Results
      were comparable when assuming no difference in TLR risk between Endeavor, Taxus
      and Xience. CONCLUSIONS: When outcomes from trials of diabetic populations are
      analysed and used in a budget-impact model from a US payer perspective, the use
      of Cypher is associated with lower TLR rates, which translates into large
      potential cost savings.

PMID- 21729836
TI  - Relationship between tissue characterisations with 40 MHz intravascular
      ultrasound imaging and slow flow during coronary intervention.
AB  - AIMS: To evaluate the plaque characteristics that predispose to the slow flow
      phenomenon during percutaneous coronary intervention (PCI). The slow flow
      phenomenon is a serious complication of PCI and is associated with poor
      prognosis. It is difficult to predict this phenomenon from greyscale
      intravascular ultrasound (IVUS) data obtained before PCI. iMapTM is a new
      software package for assessing plaque composition from data obtained by 40 MHz
      IVUS imaging. METHODS AND RESULTS: Ninety-five consecutive patients underwent 40
      MHz IVUS, including 33 with acute coronary syndrome. Plaque volume was calculated
      by IVUS and plaque components were detected by iMap software. Plaques were
      characterised as fibrotic, lipidic, necrotic, or calcified. Correlations among
      plaque characteristics and the slow flow phenomenon were analysed. Slow flow
      during PCI was observed in 11 patients (11.6%). Both the absolute volume and
      percentage of necrotic plaque were significantly higher in the slow flow group
      than the normal flow group (43.3+/-33.5 mm3 vs. 20.1+/-17.2 mm3, p=0.0004, 19.7+/
      5.1% vs. 14.6+/-8.3%, p=0.047). Receiver-operating characteristic analysis showed
      that the necrotic plaque volume and necrotic plaque ratio were significantly
      better predictors of slow flow during PCI compared with total plaque volume. The
      cut-off value of necrotic plaque volume for predicting slow flow was 21.6 mm3
      (sensitivity of 81.8% and specificity of 61.9%). CONCLUSIONS: Characterisation of
      plaque by IVUS with iMap analysis may predict slow flow during PCI.

PMID- 21729837
TI  - Tissue characterisation of atherosclerotic plaque in the left main: an in vivo
      intravascular ultrasound radiofrequency data analysis.
AB  - AIMS: To characterise plaque phenotypes in the left main stem (LMS) and the
      proximal left anterior descending (LAD) coronary artery using virtual histology
      assisted intravascular ultrasound (VH-IVUS). METHODS AND RESULTS: Patients with
      IVUS pullbacks including no less than the proximal 30 mm of the LAD and through
      the ostium of the left main were identified from a global IVUS registry. Plaque
      composition and phenotype frequency in the LMS and five consecutive non
      overlapping 6 mm segments in the LAD were studied, resulting in six analysed
      segments per patient. There were 74 patients (72% male, mean age 65 years). The
      median LMS length was 5.4 mm (IQR 2.8-8.7 mm). The percent of fibrofatty plaque
      was greater in the LMS compared to the proximal LAD segments (27.9% [20.0-39.2]
      vs. 17.3% [12.2-23.1], p<0.001). Dense calcium and necrotic core content was less
      prevalent in the LMS compared to the LAD segments (2.5% [0.9-4.7] vs. 7.9% [4.1
      12.3], p<0.001; and 8.0% [3.7-11.8] vs. 14% [9.2-17.9], p<0.001). The frequency
      of thin cap fibroatheroma (TCFA) was higher in the LAD compared with LMS (0% vs.
      16.9% [4.9-34.5], p<0.001). Within the LAD, TCFA was most frequently observed in
      the second 6 mm segment, 12 mm from the ostium. CONCLUSIONS: TCFA was present
      more frequently in the proximal LAD than LMS, supporting the notion that plaque
      rupture occurs in non-uniform locations throughout the coronary tree and
      preferentially spares the LMS.

PMID- 21729838
TI  - Optical coherence tomography at follow-up after percutaneous coronary
      intervention: relationship between procedural dissections, stent strut
      malapposition and stent healing.
AB  - AIMS: To analyse the relationship between strut apposition as visualised with
      optical coherence tomography (OCT) at follow-up and clinical and procedural
      characteristics at stent implantation, and to examine the relationship between
      strut apposition and stent healing. METHODS AND RESULTS: Twenty-eight coronary
      lesions were evaluated. The lesion morphology before stent implantation was
      described from the baseline angiogram. Strut apposition at follow-up was divided
      into: (I) apposed struts, (II) struts overlying side branch ostia, (III)
      malapposed and (IV) protruding struts. Since malapposed and protruding struts
      often occurred in the same lesions, these were divided into two groups: lesions
      without (n=20) and lesions with (n=8) the presence of these struts. The thickness
      of strut coverage was used as a surrogate for stent healing. We analysed 5,159
      struts. Sixteen were malapposed and 216 were protruding. Lesions with malapposed
      and/or protruding struts at OCT follow-up were more frequently associated with
      acute coronary syndrome (ACS) and procedure related dissections at stent
      implantation than lesions without. There was a tendency towards a less pronounced
      strut coverage over malapposed and protruding struts, as compared to apposed
      struts. CONCLUSIONS: ACS and procedural dissections at stent implantation may be
      related to strut malapposition/protrusion at follow-up, which may influence the
      degree of strut coverage.

PMID- 21729839
TI  - Paclitaxel-iopromide coated balloon followed by "bail-out" bare metal stent in
      porcine iliofemoral arteries: first report on biological effects in peripheral
      circulation.
AB  - AIMS: Despite recent abundance of data on drug-coated balloon technology, the
      biological effects of paclitaxel coated balloon (PCB) treatment followed by bare
      metal stent (BMS) implantation in peripheral arteries (simulating bail-out
      stenting, a common clinical scenario), have not been published. METHODS AND
      RESULTS: PCB technology containing a paclitaxel-iopromide coating and identical
      iopromide-coated controls (without paclitaxel) were used in 16 porcine ilio
      femoral arteries. The biological effects of inflating one (PCBx1) or two
      sequential (PCBx2) paclitaxel coated balloons before BMS implantation were
      compared to the single application of a control balloon (CCBx1; contrast coated
      balloons). At 30 days PCBx2 displayed significantly reduced late lumen loss by
      angiography (58% reduction vs. CCBx1; p=0.04) and neointimal area by
      histomorphometry (35% reduction vs. CCBx1 and 30% vs. PCBx1; p=0.02). Similarly,
      percent area stenosis in the PCBx2 group was reduced by 45% as compared to CCBx1
      and PCBx1 (p=0.04). At this time, all parameters of vessel wall healing
      (including injury score, inflammation, and endothelialisation) following drug
      coated balloon treatment were comparable to the control group. CONCLUSIONS:
      Paclitaxel delivery to porcine ilio-femorals using PCB followed by BMS
      implantation effectively decreased neointimal proliferation. More extensive and
      prolonged proliferative response of the vessel after stenting (necessitating
      higher drug dose) could potentially explain the undetectable effect of PEBx1
      relative to CCBx1 in this pilot study. Histological analysis confirmed the safety
      and biocompatibility of PCB technology.

PMID- 21729840
TI  - Virtual bench testing of new generation coronary stents.
AB  - AIMS: The aim of this study was to compare the stent strut apposition and stent
      induced vessel wall stresses of currently used coronary stent designs. This may
      help to better understand their clinical performance and provide the insights
      necessary for further optimisation. METHODS AND RESULTS: We compared the stent
      strut apposition of six different stent designs when deployed (at 12 atm) in an
      idealised stenosed vessel using a novel approach based on finite element
      simulations. Additional insights into the mechanical behaviour of the
      investigated stents were obtained by virtually quantifying the stent induced
      vessel wall stresses. For the investigated stenosed vessel model, the percentage
      of malapposed struts (distance to wall>10 um) ranged between 9% (Integrity stent)
      and 43% (Promus Element stent). The largest strut-artery distances were observed
      at the plaque shoulders. The 95 percentile of the axial stress within the intima
      ranges from 32 (Promus Element stent) to 83 kPa (Liberte stent). Stress peaks
      were mainly located at the inner curvatures of the vessel model and at the stent
      ends. CONCLUSIONS: For the investigated case, considerable differences were
      observed between the studied stent platforms in terms of stent strut apposition
      and stent induced vessel wall stresses. These differences in mechanical behaviour
      may help to explain clinical observations.

PMID- 21729841
TI  - Percutaneous versus surgical closure of secundum atrial septal defects: a
      systematic review and meta-analysis of currently available clinical evidence.
AB  - AIMS: To summarise data from studies comparing surgical (SC) versus percutaneous
      closure (PC) of atrial septal defects (ASDs). METHODS AND RESULTS: Electronic
      databases, journals and major international conference proceedings were
      systematically searched for pertinent clinical studies comparing the two methods
      of closure (percutaneous and surgical) published up to December 2008, including
      only those reporting on more than 20 patients. Primary endpoints: occurrence of
      death and of total and major early complications. Thirteen original studies
      (3,082 patients) were included. All studies were non-randomised. One death was
      reported in the surgical group (0.08%; 95% C.I. 0-0.23%). Analysis of
      postprocedural complications showed a 31% rate (95% CI 21-41%) in SC patients and
      a 6.6% rate (95% CI 3.9-9.2%) in PC subjects. The adjusted OR for SC vs. PC total
      complications was 5.4 (95% CI 2.96-9.84; p<0.0001), significantly in favour of
      PC. The postprocedural major complication rate was 6.8% (95% CI 4-9.5%) in SC
      patients and 1.9% (95% CI 0.9-2.9%) in PC patients. The adjusted OR for SC vs. PC
      major complications was 3.81 (95% CI 2.7-5.36; p=0.006), again favouring PC.
      CONCLUSIONS: The largest cohort to date of patients with secundum ASD shows that
      treatment by a percutaneous approach has a significantly lower rate of either
      total or major early postprocedural complications compared to surgery.

PMID- 21729842
TI  - Optical coherence tomography (OCT) of overlapping bioresorbable scaffolds: from
      benchwork to clinical application.

PMID- 21729843
TI  - How should I treat severe calcific coronary artery disease?
AB  - BACKGROUND: An 80-year-old man with limiting angina pectoris. INVESTIGATION:
      Physical examination, laboratory tests, echocardiography, exercise ECG, coronary
      arteriography, pressure wire assessment. DIAGNOSIS: Single severe calcific
      coronary artery disease. TREATMENT: Elective percutaneous coronary intervention
      (PCI) for calcific mid-vessel stenosis with rotational and excimer laser
      atherectomy.

PMID- 21729844
TI  - Tools & techniques: PFO/ASD closure.

PMID- 21729845
TI  - Minimizing the risk of falling.

PMID- 21729846
TI  - Helping those with hoarding behaviors.
AB  - Hoarding--the excessive acquisition of and failure to discard possessions, which
      preclude the appropriate use of living spaces--undermines safety and health by
      increasing risk for fire, falls, and infections. Hoarding does not result from
      deprivation early in life, nor are elders with hoarding behaviors merely "thrifty
      or frugal." Up to 64% of elders with hoarding behaviors have self-care deficits.
      Comorbid depression, anxiety, alcohol dependence, physical trauma, and damage to
      the prefrontal and orbitofrontal cortex are common. Hoarding was historically
      viewed as a variant of obsessive-compulsive disorder (OCD), but compulsive
      hoarding is a symptom in just 24% of all OCDs. Approximately half of elders with
      hoarding behaviors suffer from psychiatric conditions, mostly major depression
      and mood disorders. Treating elders with hoarding behavior in a medical
      psychiatric model is a complex matter that may include prescription medication if
      an underlying condition contributes to the problem. Hoarding behavior results in
      placement in a nursing facility when squalor poses a health or safety issue.

PMID- 21729847
TI  - Benchmarking 2010: measuring long-term care and consultant pharmacy practice.
AB  - The American Society of Consultant Pharmacists, with support from the pharmacy
      management software company QS/1, has completed its 2010 survey to determine
      industry standards for long-term care pharmacy operations, consultant pharmacist
      practice, and the use of health information technology in the long-term care
      setting. The report presents data collected in this annual business benchmarking
      survey. Examples of data include gross profit margins of long-term care/closed
      door pharmacies, pharmacists' salaries, prescription payer mix, consultant
      pharmacist productivity and contracting, and implementation of technology
      solutions such as ePrescribing, electronic medication administration records,
      electronic medical records, and automated dispensing.

PMID- 21729848
TI  - Pharmacist identification of medication-related problems in the home care
      setting.
AB  - OBJECTIVE: To identify medication-related problems (MRPs) in home care patients.
      DESIGN: A prospective case series involving pharmacist medication review of
      patient charts. SETTING: A nonprofit agency serving the disabled and elderly of
      Rockingham County, North Carolina. PATIENTS, PARTICIPANTS: Patients living in
      their homes, who qualify for home health care and who take eight or more
      medications. INTERVENTIONS: Patients identified received at least one medication
      review performed by a pharmacist. Six types of MRPs were identified.
      Recommendations to resolve such MRPs were sent to the prescriber for analysis.
      MAIN OUTCOME MEASURES: Outcome measures include MRPs identified, recommendations,
      and prescriber acceptance. RESULTS: 380 charts received medication reviews from
      July 2007 through June 2009, and 148 (39%) required pharmacist intervention. A
      total of 232 MRPs were identified during the review process. Of the problems
      identified, suboptimal therapy (28%) and use of unnecessary drugs (24%) were most
      common. Discontinuing a drug (38.6%) and consulting the prescriber (23.2%)
      comprised the majority of the recommendations. CONCLUSIONS: Pharmacists
      successfully identified a large number of MRPs not previously identified by other
      health care providers. Unnecessary drug use in home care patients was among the
      highest MRP noted. Discontinuation of an unnecessary drug was the most
      recommended resolution to the MRP. Prescribers respond positively to suggestions
      made by pharmacists regarding MRPs.

PMID- 21729849
TI  - The impact of pharmacist interventions on the inappropriate use of acid
      suppression therapy.
AB  - OBJECTIVE: The inappropriate use of acid-suppression therapy (AST) in non
      intensive care unit patients contributes to inappropriate polypharmacy, drug
      interactions, community- and hospital-acquired pneumonia, and increased health
      care expenditures for institutions and individuals. The purpose of this study was
      to determine whether clinical pharmacist interventions significantly decreased
      the rate of inappropriately used AST. DESIGN: A single group, pre-test post-test.
      SETTING: The Geriatric Evaluation and Management unit in the St. Louis Veterans
      Affairs Medical Center. PATIENTS: All patients admitted between July 1, 2006,
      through April 30, 2007 (control group), and May 1, 2007, through February 28,
      2008 (PharmD group), were evaluated. All patients with a minimum length of stay
      of seven days were eligible for inclusion. Data were obtained from the
      Computerized Patient Record System regarding the use of proton-pump inhibitors,
      histamine-2 receptor antagonists, sucralfate, and the indication for these
      therapies. INTERVENTIONS: A clinical pharmacist was present during the weekly
      interdisciplinary team rounds to make recommendations in the intervention group,
      compared with a nonpharmacist control group. OUTCOME MEASURES: The percent of
      patients on these therapies without an appropriate indication (International
      Classification of Diseases, 9th Revision) were identified from the chart review,
      and comparisons were made between the control and PharmD groups. RESULTS: A total
      of 142 and 151 patients were admitted during the control and PharmD arms,
      respectively. Of these patients, 117 in each group were eligible for inclusion in
      the analysis. The primary outcome, the number of patients receiving AST prior to
      discharge without an appropriate indication, occurred 46.2% (54/117) versus 23.9%
      (28/117) (P = 0.001) in the control and PharmD groups, respectively. CONCLUSIONS:
      This study examined the impact of pharmacists' active participation in
      interdisciplinary team rounds compared with a nonpharmacist control group. These
      results demonstrate pharmacist participation associated with potential cost
      savings and improved patient care.

PMID- 21729850
TI  - Insulin pens vs. vials and syringes: the pharmacist's role in individualizing
      therapy.
AB  - As pharmacists strive for tighter glucose control in their patients, several
      considerations exist including the selection of insulin delivery administration
      methods. Traditionally, insulin administration using vials and syringes has been
      common, but insulin pens are also a viable option. Insulin pens have been shown
      to increase patient autonomy, which may impact adherence. Elderly patients, who
      may suffer from dexterity and visual impairment, have been shown to prefer
      insulin pens because they are easier to use. Although insulin pens are more
      expensive per mL, some patients may find an economic advantage with insulin pens
      based on copays and beyond-use dating. In long-term care settings, the additional
      cost of insulin pens may be offset by the reduced insulin-administration time.
      Pharmacists are well suited to advocate for their patients and to help select the
      insulin administration method that considers individual limitations and fiscal
      realities, and will best support the patient's disease management.

PMID- 21729851
TI  - Health buzzwords: speaking a new language.

PMID- 21729852
TI  - It's complicated.

PMID- 21729853
TI  - "Caution! Contents should be cold": developing a whole-body hypothermia program.
AB  - Hypoxic-ischemic encephalopathy (HIE) is characterized as brain injury that
      results from lack of oxygen or blood flow to the brain in the perinatal period.
      Neonatal whole-body hypothermia and selective head cooling are becoming
      increasingly common care practices across the U.S. and Canada for infants with
      moderate-to-severe HIE because of the demonstrated ability of these approaches to
      reduce reperfusion injury to the brain. Health care professionals must develop a
      clinical care path for these fragile infants. For best results, induced
      hypothermia should be initiated within six hours of birth; therefore, care must
      be organized and provided without delay. This article provides bedside clinicians
      with care recommendations for infants being treated with these new interventions.

PMID- 21729854
TI  - Tracheostomy in infants: parent education for home care.
AB  - Children with tracheostomies are increasingly discharged home for continued care
      by their parents. Nurses are responsible for providing these parents with the
      extensive education required for a smooth and successful transition to home care.
      This article is intended to help neonatal and pediatric nurses to effectively
      prepare the parents of an infant with a tracheostomy to provide safe, quality
      care to their child after being discharged from an acute care setting to their
      home. This article discusses the knowledge, attitudes, and skills the parents are
      required to acquire prior to the infant's discharge. Home ventilation, airway
      management, suctioning, tracheostomy care, emergency management, safe home
      environment, equipment for continuous or intermittent ventilation, and supplies
      necessary for care are some of the topics discussed.

PMID- 21729855
TI  - Developmentally supportive care in the neonatal intensive care unit: an
      occupational therapist's role.
AB  - The role of a pediatric occupational therapist (OT) in the NICU is to provide
      comprehensive services, including evaluation, treatment, education, decision
      making, family support, and discharge planning. It may also include early
      intervention services or outpatient pediatric rehabilitation services. This
      article will address the need for developmentally supportive care in the NICU,
      and specifically addresses the role of an OT in this setting. It will explain how
      crucial collaboration between team members can be in providing quality,
      comprehensive care for these neonates. In addition, it will address the important
      role of the parent in this setting for developmentally supportive care while in
      the NICU and follow-up intervention upon discharge.

PMID- 21729856
TI  - Bosentan.

PMID- 21729857
TI  - Evaluation of the prothrombin time, aPTT, and platelet count in the bleeding
      infant.

PMID- 21729859
TI  - Are you prepared for the digital era?

PMID- 21729860
TI  - Late preterm infants: steps to success.

PMID- 21729861
TI  - Anatomy of a lawsuit.

PMID- 21729862
TI  - The Grandparent's Journey.

PMID- 21729866
TI  - A statistical framework for biomarker discovery in metabolomic time course data.
AB  - MOTIVATION: Metabolomics is the study of the complement of small molecule
      metabolites in cells, biofluids and tissues. Many metabolomic experiments are
      designed to compare changes observed over time under two experimental conditions
      or groups (e.g. a control and drug-treated group) with the goal of identifying
      discriminatory metabolites or biomarkers that characterize each condition. A
      common study design consists of repeated measurements taken on each experimental
      unit thus producing time courses of all metabolites. We describe a statistical
      framework for estimating time-varying metabolic profiles and their within-group
      variability and for detecting between-group differences. Specifically, we propose
      (i) a smoothing splines mixed effects (SME) model that treats each longitudinal
      measurement as a smooth function of time and (ii) an associated functional test
      statistic. Statistical significance is assessed by a non-parametric bootstrap
      procedure. RESULTS: The methodology has been extensively evaluated using
      simulated data and has been applied to real nuclear magnetic resonance
      spectroscopy data collected in a preclinical toxicology study as part of a larger
      project lead by the COMET (Consortium for Metabonomic Toxicology). Our findings
      are compatible with the previously published studies. AVAILABILITY: An R script
      is freely available for download at http://www2.imperial.ac.uk/~gmontana/sme.htm.

PMID- 21729867
TI  - Identification and characterization of chondrogenic progenitor cells in the
      fascia of postnatal skeletal muscle.
AB  - Intramuscular injection of bone morphogenetic proteins (BMPs) has been shown to
      induce ectopic bone formation. A chondrogenic phase is typically observed in this
      process, which suggests that there may exist a chondrogenic subpopulation of
      cells residing in skeletal muscle. Two prospective cell populations were isolated
      from rat skeletal muscle: fascia-derived cells (FDCs), extracted from gluteus
      maximus muscle fascia (epimysium) and muscle-derived cells (MDCs) isolated from
      the muscle body. Both populations were investigated for their cell surface marker
      profiles (flowcytometry analysis), proliferation rates as well as their myogenic
      and chondrogenic potentials. The majority of FDCs expressed mesenchymal stromal
      cell markers but not endothelial cell markers. FDCs underwent chondrogenic
      differentiation after BMP4 treatment in vitro, but not myogenic differentiation.
      Although MDCs showed chondrogenic potential, they expressed the myogenic cell
      marker desmin and readily underwent myogenic differentiation in vitro; however,
      the chondrogenic potential of the MDCs is confounded by the presence of FDC-like
      cells residing in the muscle perimysium and endomysium. To clarify the role of
      the muscle-derived myogenic cells in chondrogenesis, mixed pellets with varying
      ratios of FDCs and L6 myoblasts were formed and studied for chondrogenic
      potential. Our results indicated that the chondrogenic potential of the mixed
      pellets decreased with the increased ratio of myogenic cells to FDCs supporting
      the role of FDCs in chondrogenesis. Taken together, our results suggest that non
      myogenic cells residing in the fascia of skeletal muscle have a strong
      chondrogenic potential and may represent a novel donor cell source for cartilage
      regeneration and repair.

PMID- 21729868
TI  - Zinc-finger transcription factors are associated with guanine quadruplex motifs
      in human, chimpanzee, mouse and rat promoters genome-wide.
AB  - Function of non-B DNA structures are poorly understood though several
      bioinformatics studies predict role of the G-quadruplex DNA structure in
      transcription. Earlier, using transcriptome profiling we found evidence of
      widespread G-quadruplex-mediated gene regulation. Herein, we asked whether
      potential G-quadruplex (PG4) motifs associate with transcription factors (TF).
      This was analyzed using 220 position weight matrices [designated as transcription
      factor binding sites (TFBS)], representing 187 unique TF, in >75,000 genes in
      human, chimpanzee, mouse and rat. Results show binding sites of nine TFs,
      including that of AP-2, SP1, MAZ and VDR, occurred significantly within 100 bases
      of the PG4 motif (P < 1.24E-10). PG4-TFBS combinations were conserved in
      'orthologously' related promoters across all four organisms and were associated
      with >850 genes in each genome. Remarkably, seven of the nine TFs were zinc
      finger binding proteins indicating a novel characteristic of PG4 motifs. To test
      these findings, transcriptome profiles from human cell lines treated with G
      quadruplex-specific molecules were used; 66 genes were significantly
      differentially expressed across both cell-types, which also harbored conserved
      PG4 motifs along with one/more of the nine TFBS. In addition, genes regulated by
      PG4-TFBS combinations were found to be co-regulated in human tissues, further
      emphasizing the regulatory significance of the associations.

PMID- 21729869
TI  - CKI isoforms alpha and epsilon regulate Star-PAP target messages by controlling
      Star-PAP poly(A) polymerase activity and phosphoinositide stimulation.
AB  - Star-PAP is a non-canonical, nuclear poly(A) polymerase (PAP) that is regulated
      by the lipid signaling molecule phosphatidylinositol 4,5 bisphosphate
      (PI4,5P(2)), and is required for the expression of a select set of mRNAs. It was
      previously reported that a PI4,5P(2) sensitive CKI isoform, CKIalpha associates
      with and phosphorylates Star-PAP in its catalytic domain. Here, we show that the
      oxidative stress-induced by tBHQ treatment stimulates the CKI mediated
      phosphorylation of Star-PAP, which is critical for both its polyadenylation
      activity and stimulation by PI4,5P(2). CKI activity was required for the
      expression and efficient 3'-end processing of its target mRNAs in vivo as well as
      the polyadenylation activity of Star-PAP in vitro. Specific CKI activity
      inhibitors (IC261 and CKI7) block in vivo Star-PAP activity, but the knockdown of
      CKIalpha did not equivalently inhibit the expression of Star-PAP targets. We show
      that in addition to CKIalpha, Star-PAP associates with another CKI isoform,
      CKIepsilon in the Star-PAP complex that phosphorylates Star-PAP and complements
      the loss of CKIalpha. Knockdown of both CKI isoforms (alpha and epsilon) resulted
      in the loss of expression and the 3'-end processing of Star-PAP targets similar
      to the CKI activity inhibitors. Our results demonstrate that CKI isoforms alpha
      and epsilon modulate Star-PAP activity and regulates Star-PAP target messages.

PMID- 21729870
TI  - Next-generation insights into regulatory T cells: expression profiling and FoxP3
      occupancy in Human.
AB  - Regulatory T-cells (Treg) play an essential role in the negative regulation of
      immune answers by developing an attenuated cytokine response that allows
      suppressing proliferation and effector function of T-cells (CD4(+) Th). The
      transcription factor FoxP3 is responsible for the regulation of many genes
      involved in the Treg gene signature. Its ablation leads to severe immune
      deficiencies in human and mice. Recent developments in sequencing technologies
      have revolutionized the possibilities to gain insights into transcription factor
      binding by ChiP-seq and into transcriptome analysis by mRNA-seq. We combine FoxP3
      ChiP-seq and mRNA-seq in order to understand the transcriptional differences
      between primary human CD4(+) T helper and regulatory T-cells, as well as to study
      the role of FoxP3 in generating those differences. We show, that mRNA-seq allows
      analyzing the transcriptomal landscape of T-cells including the expression of
      specific splice variants at much greater depth than previous approaches, whereas
      50% of transcriptional regulation events have not been described before by using
      diverse array technologies. We discovered splicing patterns like the expression
      of a kinase-dead isoform of IRAK1 upon T-cell activation. The immunoproteasome is
      up-regulated in both Treg and CD4(+) Th cells upon activation, whereas the
      'standard' proteasome is up-regulated in Tregs only upon activation.

PMID- 21729871
TI  - Towards resolving the transcription factor network controlling myelin gene
      expression.
AB  - In the central nervous system (CNS), myelin is produced from spirally-wrapped
      oligodendrocyte plasma membrane and, as exemplified by the debilitating effects
      of inherited or acquired myelin abnormalities in diseases such as multiple
      sclerosis, it plays a critical role in nervous system function. Myelin sheath
      production coincides with rapid up-regulation of numerous genes. The complexity
      of their subsequent expression patterns, along with recently recognized
      heterogeneity within the oligodendrocyte lineage, suggest that the regulatory
      networks controlling such genes drive multiple context-specific transcriptional
      programs. Conferring this nuanced level of control likely involves a large
      repertoire of interacting transcription factors (TFs). Here, we combined novel
      strategies of computational sequence analyses with in vivo functional analysis to
      establish a TF network model of coordinate myelin-associated gene transcription.
      Notably, the network model captures regulatory DNA elements and TFs known to
      regulate oligodendrocyte myelin gene transcription and/or oligodendrocyte
      development, thereby validating our approach. Further, it links to numerous TFs
      with previously unsuspected roles in CNS myelination and suggests collaborative
      relationships amongst both known and novel TFs, thus providing deeper insight
      into the myelin gene transcriptional network.

PMID- 21729872
TI  - Musculoskeletal diseases--tendon.
AB  - INTRODUCTION: Tendons establish specific connections between muscles and the
      skeleton by transferring contraction forces from skeletal muscle to bone thereby
      allowing body movement. Tendon physiology and pathology are heavily dependent on
      mechanical stimuli. Tendon injuries clinically represent a serious and still
      unresolved problem since damaged tendon tissues heal very slowly and no surgical
      treatment can restore a damaged tendon to its normal structural integrity and
      mechanical strength. Understanding how mechanical stimuli regulate tendon tissue
      homeostasis and regeneration will improve the treatment of adult tendon injuries
      that still pose a great challenge in today's medicine. SOURCE OF DATA: This
      review summarizes the current status of tendon treatment and discusses new
      directions from the point of view of cell-based therapy and regenerative medicine
      approach. We searched the available literature using PubMed for relevant original
      articles and reviews. GROWING POINTS: Identification of tendon cell markers has
      enabled us to study precisely tendon healing and homeostasis. Clinically, tissue
      engineering for tendon injuries is an emerging technology comprising elements
      from the fields of cellular source, scaffold materials, growth factors/cytokines
      and gene delivering systems. AREAS TIMELY FOR DEVELOPING RESEARCH: The clinical
      settings to establish appropriate microenvironment for injured tendons with the
      combination of these novel cellular- and molecular-based scaffolds will be
      critical for the treatment.

PMID- 21729873
TI  - The inflammatory bowel disease (IBD) susceptibility genes NOD1 and NOD2 have
      conserved anti-bacterial roles in zebrafish.
AB  - Inflammatory bowel disease (IBD), in the form of Crohn's disease (CD) or
      ulcerative colitis (UC), is a debilitating chronic immune disorder of the
      intestine. A complex etiology resulting from dysfunctional interactions between
      the intestinal immune system and its microflora, influenced by host genetic
      susceptibility, makes disease modeling challenging. Mutations in NOD2 have the
      highest disease-specific risk association for CD, and a related gene, NOD1, is
      associated with UC. NOD1 and NOD2 encode intracellular bacterial sensor proteins
      acting as innate immune triggers, and represent promising therapeutic targets.
      The zebrafish has the potential to aid in modeling genetic and environmental
      aspects of IBD pathogenesis. Here, we report the characterization of the Nod
      signaling components in the zebrafish larval intestine. The nod1 and nod2 genes
      are expressed in intestinal epithelial cells and neutrophils together with the
      Nod signaling pathway genes ripk2, a20, aamp, cd147, centaurin b1, erbin and grim
      19. Using a zebrafish embryo Salmonella infection model, morpholino-mediated
      depletion of Nod1 or Nod2 reduced the ability of embryos to control systemic
      infection. Depletion of Nod1 or Nod2 decreased expression of dual oxidase in the
      intestinal epithelium and impaired the ability of larvae to reduce intracellular
      bacterial burden. This work highlights the potential use of zebrafish larvae in
      the study of components of IBD pathogenesis.

PMID- 21729874
TI  - Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome.
AB  - Mutations in the imprinted CDKN1C gene are associated with the childhood
      developmental disorder Beckwith-Wiedemann syndrome (BWS). Multiple mouse models
      with deficiency of Cdkn1c recapitulate some aspects of BWS but do not exhibit
      overgrowth of the newborn, a cardinal feature of patients with BWS. In this
      study, we found that Cdkn1c mutants attained a 20% increase in weight during
      gestation but experienced a rapid reversal of this positive growth trajectory
      very late in gestation. We observed a marked effect on placental development
      concurrently with this loss of growth potential, with the appearance of large
      thrombotic lesions in the labyrinth zone. The trilaminar trophoblast layer that
      separates the maternal blood sinusoids from fetal capillaries was disordered with
      a loss of sinusoidal giant cells, suggesting a role for Cdkn1c in maintaining the
      integrity of the maternal-fetal interface. Furthermore, the overgrowth of mutant
      pups decreased in the face of increasing intrauterine competition, identifying a
      role for Cdkn1c in the allocation of the maternal resources via the placenta.
      This work explains one difficulty in precisely replicating BWS in this animal
      model: the differences in reproductive strategies between the multiparous mouse,
      in which intrauterine competition is high, and humans, in which singleton
      pregnancies are more common.

PMID- 21729875
TI  - The zebrafish embryo as a tool for screening and characterizing pleurocidin host
      defense peptides as anti-cancer agents.
AB  - The emergence of multidrug-resistant cancers and the lack of targeted therapies
      for many cancers underscore an unmet need for new therapeutics with novel modes
      of action towards cancer cells. Host-defense peptides often exhibit selective
      cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics.
      Here, we screen 26 naturally occurring variants of the peptide pleurocidin for
      cytotoxic and anti-cancer activities, and investigate the underlying mechanism of
      action. Cytotoxicities were assessed in vitro using cell-based assays and in vivo
      using zebrafish embryos. Morphological changes were assessed by both transmission
      and scanning electron microscopy, and functional assays were performed on
      zebrafish embryos to investigate the mechanism of cell death. A total of 14
      peptides were virtually inactive against HL60 human leukemia cells, whereas 12
      caused >50% death at <=32 MUg/ml. Morphological changes characteristic of oncosis
      were evident by electron microscopy after only 1 minute of treatment with 32
      MUg/ml of variant NRC-03. Only two peptides were hemolytic. Four peptides showed
      no toxicity towards zebrafish embryos at the highest concentration tested (25
      MUM; ~64 MUg/ml) and one peptide was highly toxic, killing 4-hour-post
      fertilization (hpf) embryos immediately after exposure to 1 MUM peptide. Four
      other peptides killed embryos after 24 hours of exposure at 1 MUM. Most peptides
      caused mortality at one or more developmental stages only after continuous
      exposure (24 hours) with higher lethal doses (>=5 MUM). Pleurocidin NRC-03 bound
      to embryos and induced the release of superoxide, caused an increase in the
      number of TUNEL-positive nuclei, and caused membrane damage and the loss of
      embryonic epithelial integrity, marked by the exclusion of cells from the outer
      epithelium and the appearance of F-actin within the circumferential cells of the
      repair site. Our results indicate that specific pleurocidin variants are
      attractive cancer-selective agents that selectively induce cell death in target
      cells but leave non-target cells such as erythrocytes and non-transformed cells
      unaffected.

PMID- 21729876
TI  - A high level of liver-specific expression of oncogenic Kras(V12) drives robust
      liver tumorigenesis in transgenic zebrafish.
AB  - Human liver cancer is one of the deadliest cancers worldwide, with hepatocellular
      carcinoma (HCC) being the most common type. Aberrant Ras signaling has been
      implicated in the development and progression of human HCC, but a complete
      understanding of the molecular mechanisms of this protein in hepatocarcinogenesis
      remains elusive. In this study, a stable in vivo liver cancer model using
      transgenic zebrafish was generated to elucidate Ras-driven tumorigenesis in HCC.
      Using the liver-specific fabp10 (fatty acid binding protein 10) promoter, we
      overexpressed oncogenic kras(V12) specifically in the transgenic zebrafish liver.
      Only a high level of kras(V12) expression initiated liver tumorigenesis, which
      progressed from hyperplasia to benign and malignant tumors with activation of the
      Ras-Raf-MEK-ERK and Wnt-beta-catenin pathways. Histological diagnosis of
      zebrafish tumors identified HCC as the main lesion. The tumors were invasive and
      transplantable, indicating malignancy of these HCC cells. Oncogenic kras(V12) was
      also found to trigger p53-dependent senescence as a tumor suppressive barrier in
      the pre-neoplastic stage. Microarray analysis of zebrafish liver hyperplasia and
      HCC uncovered the deregulation of several stage-specific and common biological
      processes and signaling pathways responsible for kras(V12)-driven liver
      tumorigenesis that recapitulated the molecular hallmarks of human liver cancer.
      Cross-species comparisons of cancer transcriptomes further defined a HCC-specific
      gene signature as well as a liver cancer progression gene signature that are
      evolutionarily conserved between human and zebrafish. Collectively, our study
      presents a comprehensive portrait of molecular mechanisms during progressive Ras
      induced HCC. These observations indicate the validity of our transgenic zebrafish
      to model human liver cancer, and this model might act as a useful platform for
      drug screening and identifying new therapeutic targets.

PMID- 21729878
TI  - Acute liver failure in Scotland between 1992 and 2009; incidence, aetiology and
      outcome.
AB  - AIM: To describe incidence, aetiology and outcome data for Scotland since the
      inception of the Scottish Liver Transplant Unit (SLTU) in 1992. BACKGROUND: Acute
      liver failure (ALF) is a rare but frequently fatal condition. Few studies have
      adequate patient numbers to draw convincing conclusions over demographic
      features, aetiology and outcome. DESIGN: Statistical analysis of prospectively
      collected data on aetiology, demographic, clinical and outcome of all admissions,
      including those with ALF, to the SLTU. METHODS: Incidence data presented for
      admissions and ALF. Descriptive frequencies for aetiology, clinical, demographic
      and outcome data presented; including split analysis for paracetamol and non
      paracetamol aetiologies. Univariate and multivariate analysis of admission
      factors predictive of outcome is described. RESULTS: Nine hundred and forty-nine
      patients were admitted to the SLTU between 1992 and 2009. Five hundred and twenty
      four patients had ALF. The annual incidence of ALF in the Scottish population is
      0.62 per 100,000 and paracetamol overdose (POD) was the largest causative factor;
      responsible for 0.43 cases of ALF per 100,000 population per year. The odds ratio
      (OR) of transplantation or death was 0.47 in the POD group compared to other
      aetiologies; yet of not being a transplant candidate having met the Kings College
      Hospital poor prognostic criteria OR was 4.9. Of admissions listed for transplant
      76.0% were transplanted. Of those listed and not transplanted mortality was
      approaching 100% and 76.1% of those transplanted survived to discharge.
      CONCLUSION: This large, prospective, single centre study with a defined
      geographical area and well-recorded population provides accurate data regarding
      ALF between 1992 and 2009.

PMID- 21729877
TI  - The feelgood mutation in zebrafish dysregulates COPII-dependent secretion of
      select extracellular matrix proteins in skeletal morphogenesis.
AB  - Craniofacial and skeletal dysmorphologies account for the majority of birth
      defects. A number of the disease phenotypes have been attributed to abnormal
      synthesis, maintenance and composition of extracellular matrix (ECM), yet the
      molecular and cellular mechanisms causing these ECM defects remain poorly
      understood. The zebrafish feelgood mutant manifests a severely malformed head
      skeleton and shortened body length due to defects in the maturation stage of
      chondrocyte development. In vivo analyses reveal a backlog of type II and type IV
      collagens in rough endoplasmic reticulum (ER) similar to those found in coat
      protein II complex (COPII)-deficient cells. The feelgood mutation hinders
      collagen deposition in the ECM, but trafficking of small cargos and other large
      ECM proteins such as laminin to the extracellular space is unaffected. We
      demonstrate that the zebrafish feelgood mutation causes a single amino acid
      substitution within the DNA-binding domain of transcription factor Creb3l2. We
      show that Creb3l2 selectively regulates the expression of genes encoding distinct
      COPII proteins (sec23a, sec23b and sec24d) but find no evidence for its
      regulation of sec24c expression. Moreover, we did not detect activation of ER
      stress response genes despite intracellular accumulation of collagen and
      prominent skeletal defects. Promoter trans-activation assays show that the
      Creb3l2 feelgood variant is a hypomorphic allele that retains approximately 50%
      of its transcriptional activity. Transgenic rescue experiments of the feelgood
      phenotype restore craniofacial development, illustrating that a precise level of
      Creb3l2 transcriptional activity is essential for skeletogenesis. Our results
      indicate that Creb3l2 modulates the availability of COPII machinery in a tissue-
      and cargo-specific manner. These findings could lead to a better understanding of
      the etiology of human craniofacial and skeletal birth defects as well as adult
      onset diseases that are linked to dysregulated ECM deposition, such as arthritis,
      fibrosis or osteoporosis.

PMID- 21729879
TI  - Bias in the case-only design applied to studies of gene-environment and gene-gene
      interaction: a systematic review and meta-analysis.
AB  - BACKGROUND: The case-only study, proposed as a design specifically for assessing
      departure from multiplicative gene-environment and gene-gene interactions, is of
      considerable potential value but there are concerns about its validity. The
      objective of this study was to evaluate the extent and sources of bias in the
      case-only design by means of a systematic review and meta-regression analysis.
      METHODS: The MEDLINE, CINAHL, EMBASE and PUBMED databases were searched through
      to 7 October 2009. Studies that assessed bias in the case-only design applied to
      the study of gene-environment and gene-gene interaction were identified.
      Qualitative comments on the sources and extent of bias were extracted. A meta
      regression analysis of the ratio (IOR(CC)/IOR(CO)) of the case-control (IOR(CC))
      and case-only (IOR(CO)) interaction odds ratios was conducted based on studies in
      which both methods were applied to the same data set. RESULTS: The search yielded
      365 unique articles of which 38 met the inclusion criteria. Potential sources of
      bias in the case-only design included non-independence of genotype and exposure
      in the source population. Meta-regression analysis, based on 24 evaluations,
      produced a mean IOR(CC)/IOR(CO) of 1.06 [95% confidence interval (95% CI) 0.93
      1.22], suggesting that bias in case-only designs is not common in practice. The
      I(2) statistic indicated that 23.9% (95% uncertainty interval 0-53.9%) of the
      observed variation was due to heterogeneity between studies, which was not
      explained by any methodological characteristics of the included studies.
      CONCLUSION: As understanding of the relationships between genes and environmental
      exposures in the population improves, the case-only design may prove to be of
      considerable value.

PMID- 21729880
TI  - Modifier genes and non-genetic factors reshape anatomical deficits in Zfp423
      deficient mice.
AB  - Development of neural circuitry depends on the integration of signaling pathways
      to coordinate specification, proliferation and differentiation of cell types in
      the right number, in the right place, at the right time. Zinc finger protein 423
      (Zfp423), a 30-zinc finger transcription factor, forms alternate complexes with
      components of several developmental signaling pathways, suggesting it as a point
      of signal integration during brain development. We previously showed that mice
      lacking Zfp423 have reduced proliferation of cerebellar precursor cells,
      resulting in complete loss of vermis and variable hypoplasia of cerebellar
      hemispheres. Here, we show that Zfp423(-/-) hemisphere malformations are shaped
      by both genetic and non-genetic factors, producing distinct phenotype
      distributions in different inbred genetic backgrounds. In genetic mapping
      studies, we identify four additive modifier loci (Amzn1-4) and seven
      synthetically interacting loci (Smzn1.1-3.1) that together explain approximately
      one-third of the phenotypic variance. Strain-specific sequence polymorphism and
      expression data provide a reduced list of functional variant candidate genes at
      each modifier locus. Environmental covariates add only modest explanatory power,
      suggesting an additional stochastic component. These results provide a
      comprehensive analysis of sources of phenotype variation in a model of hindbrain
      malformation.

PMID- 21729881
TI  - Genome-wide association study identifies common variants associated with
      circulating vitamin E levels.
AB  - In genome-wide association studies (GWAS) of common genetic variants associated
      with circulating alpha- and gamma-tocopherol concentrations in two adult cohorts
      comprising 5006 men of European descent, we observed three loci associated with
      alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs),
      rs2108622 on 19pter-p13.11 (P= 1.7 * 10(-8)) and rs11057830 on 12q24.31 (P= 2.0 *
      10(-8)) and confirmed a previously reported locus marked by rs964184 on 11q23.3
      (P= 2.7 * 10(-10)). The three SNPs have been reported to be associated with lipid
      metabolism and/or regulation. We replicated these findings in a combined meta
      analysis with two independent samples, P= 7.8 * 10(-12) (rs964184 on 11q23.3 near
      BUD13, ZNF259 and APOA1/C3/A4/A5), P= 1.4 * 10(-10) (rs2108622 on 19pter-p13.11
      near CYP4F2) and P= 8.2 * 10(-9) (rs11057830 on 12q24.31 near SCARB1). Combined,
      these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels.
      In one of the two male GWAS cohorts (n= 992), no SNPs were significantly
      associated with gamma-tocopherol concentrations after including data from the
      replication sample for 71 independent SNPs with P< 1 * 10(-4) identified.

PMID- 21729882
TI  - Diverse mutational mechanisms cause pathogenic subtelomeric rearrangements.
AB  - Chromosome rearrangements are a significant cause of intellectual disability and
      birth defects. Subtelomeric rearrangements, including deletions, duplications and
      translocations of chromosome ends, were first discovered over 40 years ago and
      are now recognized as being responsible for several genetic syndromes. Unlike the
      deletions and duplications that cause some genomic disorders, subtelomeric
      rearrangements do not typically have recurrent breakpoints and involve many
      different chromosome ends. To capture the molecular mechanisms responsible for
      this heterogeneous class of chromosome abnormality, we coupled high-resolution
      array CGH with breakpoint junction sequencing of a diverse collection of
      subtelomeric rearrangements. We analyzed 102 breakpoints corresponding to 78
      rearrangements involving 28 chromosome ends. Sequencing 21 breakpoint junctions
      revealed signatures of non-homologous end-joining, non-allelic homologous
      recombination between interspersed repeats and DNA replication processes. Thus,
      subtelomeric rearrangements arise from diverse mutational mechanisms. In
      addition, we find hotspots of subtelomeric breakage at the end of chromosomes 9q
      and 22q; these sites may correspond to genomic regions that are particularly
      susceptible to double-strand breaks. Finally, fine-mapping the smallest
      subtelomeric rearrangements has narrowed the critical regions for some
      chromosomal disorders.

PMID- 21729883
TI  - Cellular toxicity of expanded RNA repeats: focus on RNA foci.
AB  - Discrete and punctate nuclear RNA foci are characteristic molecular hallmarks of
      pathogenesis in myotonic dystrophy type 1 and type 2. Intranuclear RNA inclusions
      of distinct morphology have also been found in fragile X-associated tremor ataxia
      syndrome, Huntington's disease-like 2, spinocerebellar ataxias type 8, type 10
      and type 31. These neurological diseases are associated with the presence of
      abnormally long simple repeat expansions in their respective genes whose
      expression leads to the formation of flawed transcripts with altered metabolisms.
      Expanded CUG, CCUG, CGG, CAG, AUUCU and UGGAA repeats are associated with the
      diseases and accumulate in nuclear foci, as demonstrated in variety of cells and
      tissues of human and model organisms. These repeat RNA foci differ in size,
      shape, cellular abundance and protein composition and their formation has a
      negative impact on cellular functions. This review summarizes the efforts of many
      laboratories over the past 15 years to characterize nuclear RNA foci that are
      recognized as important triggers in the mutant repeat RNA toxic gain-of-function
      mechanisms of pathogenesis in neurological disorders.

PMID- 21729884
TI  - The Clean Air Act: science, policy, and politics.

PMID- 21729885
TI  - The natural history and diagnosis of idiopathic pulmonary fibrosis: are we all on
      the same page?

PMID- 21729886
TI  - The early diagnosis of pulmonary arterial hypertension: can we do better?

PMID- 21729887
TI  - Peripherally inserted central catheters: bigger is not necessarily better.

PMID- 21729888
TI  - Point: Is low tidal volume mechanical ventilation preferred for all patients on
      ventilation? Yes.

PMID- 21729889
TI  - Counterpoint: Is low tidal volume mechanical ventilation preferred for all
      patients on ventilation? No.

PMID- 21729890
TI  - Correction for multiple testing: is there a resolution?
AB  - In most studies, many statistical tests are performed. They can be run to compare
      the groups at baseline, look at relationships among the various measures, and,
      for intervention trials, examine more than one end point. As the number of tests
      increases, so does the probability of finding at least one of them to be
      statistically significant just by chance (the problem of multiplicity). A number
      of procedures have been developed to deal with multiplicity, such as the
      Bonferroni correction, but there is continuing controversy regarding if and when
      these procedures should be used. In this article, we offer recommendations about
      when they should and should not be brought into play.

PMID- 21729891
TI  - Bone marrow-derived stem cells and respiratory disease.
AB  - Adult bone marrow contains a number of discrete populations of progenitor cells,
      including endothelial, mesenchymal, and epithelial progenitor cells and
      fibrocytes. In the context of a range of diseases, endothelial progenitor cells
      have been reported to promote angiogenesis, mesenchymal stem cells are potent
      immunosuppressors but can also contribute directly to tissue regeneration, and
      fibrocytes have been shown to induce tissue fibrosis. This article provides an
      overview of the basic biology of these different subsets of progenitor cells,
      reporting their distinct phenotypes and functional activities. The differences in
      their secretomes are highlighted, and the relative role of cellular
      differentiation vs paracrine effects of progenitor cells is considered. The
      article reviews the literature examining the contribution of progenitor cells to
      the pathogenesis of respiratory disease, and discusses recent studies using bone
      marrow progenitor cells as stem cell therapies in the context of pulmonary
      hypertension, COPD, and asthma.

PMID- 21729892
TI  - Glycemic control in the ICU.
AB  - Hyperglycemia is common in critically ill patients, with approximately 90% of
      patients treated in an ICU developing blood glucose concentrations > 110 mg/dL
      (6.1 mmol/L). Landmark trials in Leuven, Belgium, suggested that targeting
      normoglycemia (a blood glucose concentration of 80-110 mg/dL [4.4-6.1 mmol/L])
      reduced mortality and morbidity, but other investigators have not been able to
      replicate these findings. Recently, the international multicenter Normoglycemia
      in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE
      SUGAR) study reported increased mortality with this approach, and recent meta
      analyses do not support intensive glucose control for critically ill patients.
      Although the initial trials in Leuven produced enthusiasm and recommendations for
      intensive blood glucose control, the results of the NICE-SUGAR study have
      resulted in the more moderate recommendation to target a blood glucose
      concentration between 144 mg/dL and 180 mg/dL (8-10 mmol/L). As critical care
      practitioners pay greater attention to glycemic control, it has become clear that
      currently used point-of-care measuring systems are not accurate enough to target
      tight glucose control. Unresolved issues include whether increased blood glucose
      variability is inherently harmful and whether even moderate hypoglycemia can be
      tolerated in the quest for tighter blood glucose control. Future research must
      first address whether intensive glucose control can be delivered safely, and
      whether computerized decision support systems and newer technologies that allow
      accurate and continuous or near-continuous measurement of blood glucose can make
      this possible. Until such time, clinicians would be well advised to abide by the
      age-old adage to "first, do no harm."

PMID- 21729893
TI  - Long-term course and prognosis of idiopathic pulmonary fibrosis in the new
      millennium.
AB  - The American Thoracic Society and European Respiratory Society guidelines for the
      diagnosis and treatment of idiopathic pulmonary fibrosis (IPF) have been
      published recently. However, the influence, practical application, and utility of
      the prior consensus statement for IPF have never been evaluated. Demographics,
      diagnostic criteria, pulmonary function data, and disposition of patients with
      IPF evaluated at an interstitial lung disease center between 2000 and 2009 were
      analyzed. Enrollment in clinical drug trials, lung transplantation, and mortality
      also were assessed. A total of 521 patients with IPF were evaluated, with
      pulmonary function testing available in 446. In the 64% of patients without
      surgical lung biopsy, the most common major criterion not fulfilled was
      bronchoscopy. Lung transplantation was performed in 16.1% of patients, whereas
      27.4% of prescreened patients were enrolled in a prospective drug study. Patients
      with mild, moderate, and severe disease categorized by FVC % predicted had median
      survivals of 55.6, 38.7, and 27.4 months, respectively. The attrition rate of
      patients who survived beyond 5 years was attenuated in subsequent years. IPF
      remains a deadly disease with a poor prognosis. Bronchoscopy does not appear to
      be required for an accurate diagnosis. A minority of patients were accommodated
      within a clinical trial or with transplantation. Categorization by baseline FVC %
      predicted effectively discriminates groups with different long-term outcomes. Our
      analysis supports the view that the value of statements also can be realized in
      the subsequent demonstration of their impact on patient management, which might
      enable further refinements in a continuous, iterative rediscovery process.

PMID- 21729894
TI  - The research agenda in ICU telemedicine: a statement from the Critical Care
      Societies Collaborative.
AB  - ICU telemedicine uses audiovisual conferencing technology to provide critical
      care from a remote location. Research is needed to best define the optimal use of
      ICU telemedicine, but efforts are hindered by methodological challenges and the
      lack of an organized delivery approach. We convened an interdisciplinary working
      group to develop a research agenda in ICU telemedicine, addressing both
      methodological and knowledge gaps in the field. To best inform clinical decision
      making and health policy, future research should be organized around a conceptual
      framework that enables consistent descriptions of both the study setting and the
      telemedicine intervention. The framework should include standardized methods for
      assessing the preimplementation ICU environment and describing the telemedicine
      program. This framework will facilitate comparisons across studies and improve
      generalizability by permitting context-specific interpretation. Research based on
      this framework should consider the multidisciplinary nature of ICU care and
      describe the specific program goals. Key topic areas to be addressed include the
      effect of ICU telemedicine on the structure, process, and outcome of critical
      care delivery. Ideally, future research should attempt to address causation
      instead of simply associations and elucidate the mechanism of action in order to
      determine exactly how ICU telemedicine achieves its effects. ICU telemedicine has
      significant potential to improve critical care delivery, but high-quality
      research is needed to best inform its use. We propose an agenda to advance the
      science of ICU telemedicine and generate research with the greatest potential to
      improve patient care.

PMID- 21729895
TI  - Burkholderia pseudomallei infection in a child with cystic fibrosis: acquisition
      in the Western Hemisphere.
AB  - Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, is
      endemic to Southeast Asia and northern Australia but is only very rarely seen in
      patients in the United States. We report pulmonary B pseudomallei infection in a
      young girl with cystic fibrosis (CF) who had never traveled to Asia or Australia.
      Biochemical and epidemiologic investigation determined Aruba as the likely site
      of disease acquisition. This report highlights the ability of patients with CF to
      acquire this organism outside of Southeast Asia and describes an aggressive
      treatment regimen that has kept this patient culture-negative for the organism
      over a long period of time.

PMID- 21729896
TI  - Endotracheal myoepithelioma.
AB  - Myoepitheliomas have been described most commonly in salivary glands and have
      been reported elsewhere but are rare in the lung, with only six previously
      reported cases. To our knowledge, this represents the first endotracheal
      myoepithelioma. These tumors have characteristic features that distinguish them
      from other tumors, and the diagnosis is a pathologic one, based on the morphology
      and supported by immunohistochemistry. Myoepitheliomas should be considered in
      the diagnosis of any pulmonary nodule.

PMID- 21729897
TI  - Hemoptysis and spontaneous hemothorax in a patient with multifocal nodular lung
      lesions.

PMID- 21729898
TI  - A 19-year-old woman with progressive dyspnea and multiple pulmonary nodules.

PMID- 21729899
TI  - A 35-year-old patient with midscapular pain and hypertension.

PMID- 21729900
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration: one defect away
      from perfect.

PMID- 21729901
TI  - COPD and lung cancer linked at a molecular genetic level.

PMID- 21729902
TI  - Serious fun: adding summative simulation-based testing to the CHEST Challenge.

PMID- 21729903
TI  - Cysteine as a biomarker for obstructive sleep apnea.

PMID- 21729904
TI  - Active cytomegalovirus infection in nonimmunosuppressed patients in the ICU.

PMID- 21729905
TI  - Limitations inherent to the simplified Bernoulli equation explain the inaccuracy
      of Doppler echocardiographic estimates of pulmonary artery pressures in patients
      with pulmonary hypertension.

PMID- 21729906
TI  - Endobronchial ultrasound and esophageal ultrasound: just because we can, does not
      necessarily mean we should.

PMID- 21729907
TI  - Sustained visual cortex hyperexcitability in migraine with persistent visual
      aura.
AB  - Persistent aura without infarction, a rare migraine disorder, is defined by aura
      symptoms that persist for >1 week without radiological evidence of cerebral
      infarction. To unveil its pathophysiological mechanisms, this study used
      magnetoencephalography to characterize the visual cortex excitability in
      persistent aura by comparison with episodic and chronic migraine. We recruited
      six patients with persistent visual aura, 39 patients with episodic migraine [12
      in ictal phase; 27 in interictal phase (with aura, n = 9; without aura, n = 18)],
      18 patients with chronic migraine and 24 healthy controls. Five sequential blocks
      of 50 neuromagnetic prominent 100 ms responses were obtained, and the dynamic
      change in visual cortex excitability was evaluated by the percentage changes of
      individual mean prominent 100 ms amplitudes at blocks 2-5 compared with block 1,
      with a significant increase indicating potentiation. We found that in patients
      with persistent aura, there was significant potentiation during ictal periods (P
      = 0.009 and 0.006 at blocks 2 and 5, respectively), and the excitability change
      was inversely correlated with the duration of aura persistence (correlation
      coefficient -0.812, P = 0.050, block 2). The interictal recordings (n = 3) also
      showed potentiation. In terms of the other migraine spectrum disorders,
      persistent aura differed from episodic migraine in the presence of ictal
      potentiation. Persistent aura further differed from chronic migraine in the
      absence of interictal potentiation in chronic migraine. There was a higher
      percentage change of response amplitude at the end of stimulation (block 5) in
      persistent aura (43.3 +/- 11.7) than in chronic migraine (-7.6 +/- 5.5, P =
      0.006) and ictal recordings of episodic migraine (-4.9 +/- 9.6, P = 0.020).
      Normal control subjects had no significant response changes. This
      magnetoencephalographic study showed that the visual cortex in patients with
      persistent visual aura maintains a steady-state hyperexcitability without
      significant dynamic modulation. The excitability characteristic supports
      persistent visual aura as a nosological entity in migraine spectrum disorders and
      suggests a pathophysiological link to sustained excitatory effects possibly
      related to reverberating cortical spreading depression.

PMID- 21729909
TI  - Workplace violence in Hong Kong, China: nature, impact, and preparedness.
AB  - This article reports a survey of workplace violence in Hong Kong. A sizable
      number of the 1,198 organizations that were questioned reported that they had
      experienced such violence over the 2 years preceding the study, but the problem
      was not prevalent. In both the private and government sectors, nonphysical
      violence happened more frequently than physical violence, and there was a
      reported lack of preparedness of many organizations to deal with the violence.
      Compared with private organizations, government organizations experienced more
      coworker and customer violence, but more private than government organizations
      believed that workplace violence caused the loss of key employees and clients.
      Correlation analysis found that a subculture of workplace violence appears to
      emerge over time, such that the more customer violence is experienced, the more
      is coworker violence, and the more the nonphysical violence, the more the
      physical violence. These findings are discussed with reference to international
      findings.

PMID- 21729910
TI  - The impact of population heterogeneity and income inequality on homicide rates: a
      cross-national assessment.
AB  - The current research produces regression models with sample sizes from 127 to 131
      by initially employing a data set of 170 nations. The current study finds that
      ethnic heterogeneity and linguistic heterogeneity lead to higher homicide rates.
      However, religious heterogeneity has no impact on homicide rates. The present
      article also tests an interaction effect between population heterogeneity and
      income inequality. Unlike J. R. Blau and Blau (1982) and Avision and Loring
      (1986) proposition, the interaction term is not related to national homicide
      rates. The current study also discusses the theoretical implications of those
      findings.

PMID- 21729911
TI  - Models and measurement in disability: an international review.
AB  - This article reviews the theoretical basis and methods for disability
      measurement. Different methods arise from different theoretical perspectives.
      Recent efforts to develop a general international disability measure consistent
      with the social model of disability aim to produce an internationally comparable
      measure of disability with which to assess the equalisation of opportunities.
      Such a measure cannot consistently identify disabled people in need of health and
      social services. Correctly identifying those in need of these services
      particularly concerns developing countries where government revenues and
      disability services are severely limited. This review highlights the need for
      multiple disability measures to meet different purposes of measurement. The
      Washington Group general measure on disability and Katz's Activities of Daily
      Living Index are recommended as valid measures of varying functioning level
      consistent with the International Classification of Functioning, Disability and
      Health.

PMID- 21729912
TI  - Moving towards in-depth knowledge on the private health sector in low- and middle
      income countries.

PMID- 21729913
TI  - Predicting performance in contracting of basic health care to NGOs: experience
      from large-scale contracting in Uttar Pradesh, India.
AB  - Escalating costs and increasing pressure to improve health services have driven a
      trend toward contracting with the private sector to provide traditionally state
      run services. Such contracting is seen as an opportunity to combine theorized
      advantages of contracting with the efficiency of the private sector. There is
      still a limited understanding of the preconditions for successful use of
      contracting and the resources needed for their appropriate use and
      sustainability. This study assesses the large-scale contracting of 294 non
      governmental organizations (NGOs) for delivery of basic health services in Uttar
      Pradesh, a state with almost 170 million in India. Due to high rates of
      discontinuation or non-renewal of contracts based on poor performance in the
      project, a better method for selecting partners was requested. Data on
      characteristics of the NGOs (intake data) and performance/outcome monitoring
      indicators were combined to identify correlations. The results showed that NGOs
      selected were generally small but well-established, had implemented at least two
      large projects, and had more non-health experience than health experience.
      Bivariate regressions of outcome score on each input variable showed that
      training experience, proposal quality and having 'health' contained in the
      objectives of the organization were statistically significant predictors of good
      performance. Factors relating to financial capacity, staff qualification,
      previous experience with health or non-health projects, and age of establishment
      were not. A combined training plus proposal score was highly predictive of
      outcome score (beta = 1.37, P < 0.001). The combined score was found to be a much
      better predictor of outcome scores than a total score used to select NGOs (beta =
      0.073, P = 0.539). The study provides valuable information from large-scale
      contracting. Conclusions on criteria for selecting NGOs for providing basic
      health care could guide other governments choosing to contract for such services.

PMID- 21729914
TI  - Comparison of trust in public vs private health care providers in rural Cambodia.
AB  - How trust in providers affects health care-seeking behaviour is not well
      understood. Focus groups and household surveys were conducted in Cambodia to
      examine how villagers describe their trust in public and private providers, and
      to assess whether a difference exists in provider trust levels. Our findings
      suggest the reasons for trusting public and private providers differ, and that
      villagers' trust in and relationship with providers is one of the important
      considerations affecting where they seek care. People believed that public
      providers were 'honest' and 'sincere', did not 'bad mouth people' and explained
      the 'status of [the] disease'. Villagers trusted public providers for their
      skills and abilities, and for an effective referral system. In contrast,
      respondents noted that seeing private providers was 'comfortable and easy', that
      they 'come to our home' and patients can 'owe [them] some money'. Private
      providers were trusted for being very friendly and approachable, extremely
      thorough and careful, and easy to contact. Among those who sought care in the
      past 30 days, trust in the health care provider was listed as the fifth and
      second most important consideration for choosing public or private providers,
      respectively. This study illustrates the importance of trust as a unique concept
      that can affect people's choice of health care providers in a low-income country.

PMID- 21729915
TI  - Composition of pluralistic health systems: how much can we learn from household
      surveys? An exploration in Cambodia.
AB  - In spite of all efforts to build national health services, health systems of many
      low-income countries are today highly pluralistic. Households use a vast range of
      public and private health care providers, many of whom are not controlled by
      national health authorities. Experts have called on Ministries of Health to re
      establish themselves as stewards of the entire health system. Modern stewardship
      will require national and decentralized health authorities to have an overall
      view of their pluralistic health system, especially of the components outside the
      public sector. Little guidance has been provided so far on how to develop such a
      view. In this paper, we explore whether household surveys could be a source of
      information. The study builds on secondary data analysis of a household survey
      carried out in three health districts in rural Cambodia and of two national
      surveys. Cambodia is indeed an interesting case, as massive efforts by donors in
      favour of the public sector go hand in hand with a dominant role of the private
      sector in the provision of health care services. The study confirms that the
      health care sector in Cambodia is now highly pluralistic, and that the great
      majority of health seeking behaviour takes place outside the public health
      system. Our analysis of the survey also shows that the disaffection of the
      population with public health facilities varies across places, socio-economic
      groups and health problems. We illustrate how such knowledge could allow stewards
      to better identify challenges for existing or future health policies. We argue
      that a whole research programme on the composition of pluralistic health systems
      still needs to be developed. We identify some challenges and opportunities.

PMID- 21729916
TI  - Role of the private sector in the provision of immunization services in low- and
      middle-income countries.
AB  - The authors conducted a literature review on the role of the private sector in
      low- and middle-income countries. The review indicated that relatively few
      studies have researched the role of the private sector in immunization service
      delivery in these countries. The studies suggest that the private sector is
      playing different roles and functions according to economic development levels,
      the governance structure and the general presence of the private sector in the
      health sector. In some countries, generally low-income countries, the private for
      profit sector is contributing to immunization service delivery and helping to
      improve access to traditional EPI vaccines. In other countries, particularly
      middle-income countries, the private for-profit sector often acts to facilitate
      early adoption of new vaccines and technologies before introduction and
      generalization by the public sector. The not-for-profit sector plays an important
      role in extending access to traditional EPI vaccines, particularly in low-income
      countries. Not-for-profit facilities are situated in rural as well as urban areas
      and are more likely to be coordinated with public services than the private for
      profit sector. Although numerous studies on non-governmental organizations (NGOs)
      suggest that the extent of NGO provision of immunization services in low- and
      middle-income countries is substantial, the contribution of this sector is poorly
      documented, leading to a lack of recognition of its role at national and global
      levels. Studies on quality of immunization service provision at private health
      facilities suggest that it is sometimes inadequate and needs to be monitored.
      Although some articles on public-private collaboration exist, little was found on
      the extent to which governments are effectively interacting with and regulating
      the private sector. The review revealed many geographical and thematic gaps in
      the literature on the role and regulation of the private sector in the delivery
      of immunization services in low- and middle-income countries.

PMID- 21729917
TI  - Making health markets work better for poor people: the case of informal
      providers.
AB  - There has been a dramatic spread of market relationships in many low- and middle
      income countries. This spread has been much faster than the development of the
      institutional arrangements to influence the performance of health service
      providers. In many countries poor people obtain a large proportion of their
      outpatient medical care and drugs from informal providers working outside a
      regulatory framework, with deleterious consequences in terms of the safety and
      efficacy of treatment and its cost. Interventions that focus only on improving
      the knowledge of these providers have had limited impact. There is a considerable
      amount of experience in other sectors with interventions for improving the
      performance of markets that poor people use. This paper applies lessons from this
      experience to the issue of informal providers, drawing on the findings of studies
      in Bangladesh and Nigeria. These studies analyse the markets for informal health
      care services in terms of the sources of health-related knowledge for the
      providers, the livelihood strategies of these providers and the institutional
      arrangements within which they build and maintain their reputation. The paper
      concludes that there is a need to build a systematic understanding of these
      markets to support collaboration between key actors in building institutional
      arrangements that provide incentives for better performance.

PMID- 21729918
TI  - The principal-agent problems in health care: evidence from prescribing patterns
      of private providers in Vietnam.
AB  - The principal-agent problem in health care asserts that providers, being the
      imperfect agents of patients, will act to maximize their profits at the expense
      of the patients' interests. This problem applies especially where professional
      regulations are lacking and incentives exist to directly link providers' actions
      to their profits, such as a fee-for-service payment system. The current analysis
      tests for the existence of the principal-agent problem in the private health
      market in Vietnam by examining the prescribing patterns of private providers. I
      show that: (1) private providers were able to induce demand by prescribing more
      drugs than public providers for a similar illness and patient profile; (2)
      private providers were significantly more likely to prescribe injection drugs to
      gain trust among the patients; and (3) patients' education as a source of
      information and empowerment has enabled them to mitigate the demand inducement by
      the providers. The hypotheses are supported with evidence from the Vietnam
      National Health Survey 2001-02, the first and, so far, only comprehensive health
      survey in the country.

PMID- 21729919
TI  - Comparing private sector family planning services to government and NGO services
      in Ethiopia and Pakistan: how do social franchises compare across quality, equity
      and cost?
AB  - Policy makers in developing countries need to assess how public health programmes
      function across both public and private sectors. We propose an evaluation
      framework to assist in simultaneously tracking performance on efficiency, quality
      and access by the poor in family planning services. We apply this framework to
      field data from family planning programmes in Ethiopia and Pakistan, comparing
      (1) independent private sector providers; (2) social franchises of private
      providers; (3) non-government organization (NGO) providers; and (4) government
      providers on these three factors. Franchised private clinics have higher quality
      than non-franchised private clinics in both countries. In Pakistan, the costs per
      client and the proportion of poorest clients showed no differences between
      franchised and non-franchised private clinics, whereas in Ethiopia, franchised
      clinics had higher costs and fewer clients from the poorest quintile. Our results
      highlight that there are trade-offs between access, cost and quality of care that
      must be balanced as competing priorities. The relative programme performance of
      various service arrangements on each metric will be context specific.

PMID- 21729920
TI  - The private sector role in HIV/AIDS in the context of an expanded global
      response: expenditure trends in five sub-Saharan African countries.
AB  - Global financing for the HIV response has reached unprecedented levels in recent
      years. Over US$10 billion were mobilized in 2007, an effort credited with saving
      the lives of millions of people living with HIV (PLHIV). A relatively unexamined
      aspect of the global HIV response is the role of the private sector in financing
      HIV/AIDS services. As the nature of the response evolves from emergency relief to
      long-term sustainability, understanding current and potential contributions from
      the private sector is critical. This paper examines trends in private sector
      financing, management and resource consumption related to HIV/AIDS in five sub
      Saharan African countries, with a particular emphasis on the effects of recently
      scaled-up donor funding on private sector contributions. We analysed National
      Health Accounts HIV/AIDS subaccount data for Kenya, Malawi, Rwanda, Tanzania and
      Zambia between 2002 and 2006. HIV subaccounts provide comparable data on the flow
      of HIV/AIDS funding from source to use. Findings indicate that private sector
      contributions decreased in all countries except Tanzania. With regards to
      managing HIV/AIDS funds, non-governmental organizations are increasingly
      controlling the largest share of resources relative to other stakeholders,
      whereas private for-profit entities are managing fewer HIV/AIDS resources since
      the donor influx. The majority of HIV/AIDS funds were spent in the public sector,
      although a considerable amount was spent at private facilities, largely fuelled
      by out-of-pocket (OOP) payments. On the whole, OOP spending by PLHIV decreased
      over the 4-year period, with the exception of Malawi, demonstrating that PLHIV
      have increased access to free or subsidized HIV/AIDS services. Our findings
      suggest that the influx of donor funding has led to decreased private
      contributions for HIV/AIDS. The reduction in private sector investment and
      engagement raises concerns about the sustainability of HIV/AIDS programmes over
      the long term, particularly in light of current global economic crisis and
      emerging competing priorities.

PMID- 21729921
TI  - Propofol attenuates angiotensin II-induced apoptosis in human coronary artery
      endothelial cells.
AB  - BACKGROUND: Angiotensin II (Ang II) induces oxidative stress and apoptosis in
      vascular endothelial cells. We hypothesized that propofol may attenuate Ang II
      induced apoptosis in human coronary artery endothelial cells (HCAECs) and aimed
      to identify the underlying mechanisms. METHODS: Endothelial cells were pre
      treated with propofol and then stimulated with Ang II. Apoptosis was examined by
      TUNEL, DNA laddering, and caspase-3 activity assays. The effect of propofol on
      Ang II-modulated NADPH oxidase expression and activity, nitric oxide synthase III
      (NOSIII) expression and phosphorylation and activity, lipid peroxidation,
      superoxide anion generation, nitric oxide production, caspase activity, and
      protein expression of cytochrome c, Bcl-2, and C-IAP-1 were measured. RESULTS:
      Ang II induced apoptosis, which was attenuated by 50 uM propofol (P<0.05).
      Propofol ameliorated Ang II-induced NADPH oxidase expression and activation
      (P<0.01), lipid peroxidation (P<0.05), and superoxide anion generation (P<0.05),
      whereas restoring NOSIII phosphorylation and activity (P<0.01) were down
      regulated by Ang II. Propofol attenuated Ang II-modulated cytochrome c release,
      and the expression of Bcl-2 and C-IAP-1. In addition, propofol inhibited Ang II
      induced caspase-9 (P<0.01) and caspase-3 activity (P<0.01). CONCLUSIONS: Propofol
      protected HCAECs from Ang II-induced apoptosis by interfering with the generation
      of oxidative stress and redox-sensitive apoptotic pathways.

PMID- 21729922
TI  - Analysis of muscle and ovary transcriptome of Sus scrofa: assembly, annotation
      and marker discovery.
AB  - Pig (Sus scrofa) is an important organism for both agricultural and medical
      purpose. This study aims to investigate the S. scrofa transcriptome by the use of
      Roche 454 pyrosequencing. We obtained a total of 558 743 and 528 260 reads for
      the back-leg muscle and ovary tissue each. The overall 1 087 003 reads give rise
      to 421 767 341 bp total residues averaging 388 bp per read. The de novo
      assemblies yielded 11 057 contigs and 60 270 singletons for the back-leg muscle,
      12 204 contigs and 70 192 singletons for the ovary and 18 938 contigs and 102 361
      singletons for combined tissues. The overall GC content of S. scrofa
      transcriptome is 42.3% for assembled contigs. Alternative splicing was found
      within 4394 contigs, giving rise to 1267 isogroups or genes. A total of 56 589
      transcripts are involved in molecular function (40 916), biological process (38
      563), cellular component (35 787) by further gene ontology analyses. Comparison
      analyses showed that 336 and 553 genes had significant higher expression in the
      back-leg muscle and ovary each. In addition, we obtained a total of 24 214 single
      nucleotide polymorphisms and 11 928 simple sequence repeats. These results
      contribute to the understanding of the genetic makeup of S. scrofa transcriptome
      and provide useful information for functional genomic research in future.

PMID- 21729923
TI  - In silico analysis of transcription factor repertoires and prediction of stress
      responsive transcription factors from six major gramineae plants.
AB  - The interactions between transcription factors (TFs) and cis-regulatory DNA
      sequences control gene expression, constituting the essential functional linkages
      of gene regulatory networks. The aim of this study is to identify and integrate
      all putative TFs from six grass species: Brachypodium distachyon, maize, rice,
      sorghum, barley, and wheat with significant information into an integrative
      database (GramineaeTFDB) for comparative genomics and functional genomics. For
      each TF, sequence features, promoter regions, domain alignments, GO assignment,
      FL-cDNA information, if available, and cross-references to various public
      databases and genetic resources are provided. Additionally, GramineaeTFDB
      possesses a tool which aids the users to search for putative cis-elements located
      in the promoter regions of TFs and predict the functions of the TFs using cis
      element-based functional prediction approach. We also supplied hyperlinks to
      expression profiles of those TF genes of maize, rice, and barley, for which data
      are available. Furthermore, information about the availability of FOX and Ds
      mutant lines for rice and maize TFs, respectively, are also accessible through
      hyperlinks. Our study provides an important user-friendly public resource for
      functional analyses and comparative genomics of grass TFs, and understanding of
      the architecture of transcriptional regulatory networks and evolution of the TFs
      in agriculturally important cereal crops.

PMID- 21729924
TI  - Metabolic activation of furfuryl alcohol: formation of 2-methylfuranyl DNA
      adducts in Salmonella typhimurium strains expressing human sulfotransferase 1A1
      and in FVB/N mice.
AB  - Furfuryl alcohol, formed by acid- and heat-induced dehydration from pentoses, is
      found in many foodstuffs. It induced renal tubule neoplasms in male B6C3F1 mice
      and nasal neoplasms in male F344/N rats in a study of the National Toxicology
      Program (NTP). However, furfuryl alcohol was negative in the standard Ames test
      and in a battery of in vivo mutagenicity tests. Here, we show that furfuryl
      alcohol is mutagenic in Salmonella typhimurium TA100 engineered for expression of
      human sulfotransferase (SULT) 1A1. This finding suggests that furfuryl alcohol is
      converted by intracellular sulfo conjugation to 2-sulfo-oxymethylfuran, an
      electrophile reacting with DNA. We detected nucleoside adducts of 2'
      deoxyadenosine, 2'-deoxyguanosine and 2'-deoxycytidine in porcine liver DNA
      incubated with freshly prepared 2-sulfo-oxymethylfuran. The main adducts, N(2)
      ((furan-2-yl)methyl)-2'-deoxyguanosine (N(2)-MFdG) and N(6)-((furan-2-yl)methyl)
      2'-deoxyadenosine (N(6)-MFdA) were synthesized. Their structures were verified by
      NMR and mass spectrometry. Liquid chromatography-tandem mass spectrometry methods
      for the quantification of both adducts were devised. N(2)-MFdG and N(6)-MFdA were
      detected in DNA of furfuryl alcohol-exposed S.typhimurium TA100 expressing
      SULT1A1 and in DNA of liver, lung and kidney of FVB/N mice that had received ~390
      mg furfuryl alcohol/kg body wt/day via the drinking water for 28 days. In
      summary, furfuryl alcohol is converted by sulfo conjugation to a mutagen. The
      detection of N(2)-MFdG and N(6)-MFdA in renal DNA of furfuryl alcohol-treated
      mice suggests that the neoplasms observed in this tissue in the study of the NTP
      may have been induced by 2-sulfo-oxymethylfuran.

PMID- 21729925
TI  - Pleural mesothelioma side populations have a precursor phenotype.
AB  - DyeCycleViolet was used to set up the side population (SP) functional assay aimed
      at identifying subpopulations of malignant pleural mesothelioma (MPM) tumor cells
      with chemoresistance phenotype associated with ABCG2 transporter activity. Self
      renewal, chemoresistance and tumorigenicity were tested for SP and non-side
      population (NSP) cells. Tumors were characterized by mesothelin, calretinin, N
      cadherin, D2-40 and Wilms tumor 1 (WT1) immunohistochemistry. Surface expression
      of mesenchymal stem cell markers CD90, CD73 and CD105 was investigated in SP and
      NSP cells. We identified SP cells with self-renewal properties and increased
      chemoresistance in MPM cell lines and tumor-derived primary cell cultures.
      Compared with the non-SP fraction (NSP), the SP fraction led to the development
      of tumors including cells with mesothelium precursor phenotype characterized by
      mesenchymal morphology, being WT1 negative but cytoplasmic D2-40 positive and
      having a tendency of increased tumorigenicity. The same phenotypic shift was
      observed in patients with relapsing tumors after chemotherapy. Furthermore, the
      SP cells were enriched in CD105(-)(/low) expressing cells, which were small sized
      and had increased tumorigenicity compared with CD105(high) cells. Taken together,
      our results support the hypothesis that MPM CD105(-)(/low), chemoresistant small
      sized SP cells may constitute the cellular pool out of which recurrence develops.
      Further characterization of mechanisms of chemoresistance and self-renewal should
      lead to targets specific for this subpopulation in MPM patients.

PMID- 21729926
TI  - Effect of resistance training on physical performance and fear of falling in
      elderly with different levels of physical well-being.

PMID- 21729927
TI  - Interaction between myosin and a trace amount of caldesmon.
AB  - Caldesmon (CaD) is known as an actin binding protein. In this study, we proposed
      that a trace amount of caldesmon (TACD) could highly, efficiently, interact with
      myosin by producing a 'domino-like cascade' and characterized that TACD (lowest
      caldesmon/myosin molar ratio: 1/10,000) significantly increased precipitations
      and intrinsic tryptophan fluorescence intensity of myosin in both phosphorylated
      and unphosphorylated states compared to the base controls (P < 0.01). Actin
      blocked TACD-myosin interaction, suggesting that it functioned as a negative
      regulator. Since CaD is not an enzyme, the in vivo significance of the highly
      efficient TACD-myosin interaction needs further investigation.

PMID- 21729929
TI  - Right coronary artery-coronary sinus fistula demonstrated by transthoracic
      echocardiography.

PMID- 21729928
TI  - Intracellular recognition of pathogens and autophagy as an innate immune host
      defence.
AB  - Pathogen recognition is the first and crucial step in innate immunity. Molecular
      families involved in the recognition of pathogens and activation of the innate
      immune responses in immunoreactive cells include the Toll-like receptor family in
      mammals and the peptidoglycan recognition protein (PGRP) family in Drosophila,
      which sense microorganisms in an extracellular or luminal compartment. Other
      emerging families are the intracellular recognition molecules for bacteria, such
      as nucleotide binding and oligomerization domain-like receptors in mammals and
      PGRP--LE in Drosophila, several of which have been shown to detect structures of
      bacterial peptidoglycan in the host cell cytosol. Exciting advances in recent
      studies on autophagy indicate that macroautophagy (referred to here as autophagy)
      is selectively induced by intracellular recognition molecules and has a crucial
      role in the elimination of intracellular pathogens, including bacteria, viruses
      and parasites. This review discusses recent studies related to intracellular
      recognition molecules and innate immune responses to intracellular pathogens, and
      highlights the role of autophagy in innate immunity.

PMID- 21729930
TI  - Coronary pseudoaneurysm and superior vena cava occlusion in a young patient with
      multicentric Castleman's disease and antiphospholipid antibody positivity.
AB  - Castleman disease is a non-malignant proliferative disease of the lymphoid
      system. It can be unicentric or multicentric. In this report, we present a case
      of multicentric Castleman disease to which coronary artery pseudoaneurysm, vena
      cava superior occlusion, and antiphospholipid antibody positivity was
      accompanying.

PMID- 21729931
TI  - Pharmacokinetics of moxifloxacin in plasma and tissue of morbidly obese patients.
AB  - OBJECTIVES: To assess the pharmacokinetics of moxifloxacin in morbidly obese
      patients. METHODS: Twelve morbidly obese patients (2 male/10 female, age 25-61
      years, weight 98-166 kg, body mass index 43.0-58.2 kg/m(2)) scheduled for gastric
      bypass surgery were treated with 400 mg of moxifloxacin orally once daily for 3
      days and with 400 mg of moxifloxacin intravenously on day 4 (day of surgery).
      Pharmacokinetic analysis was performed on day 1 and day 4. Specimens of small
      intestine, greater omentum and subcutaneous adipose tissue were collected
      intraoperatively 1.8-3.7 h after moxifloxacin infusion. Moxifloxacin
      concentrations were determined by HPLC. RESULTS: The plasma pharmacokinetics
      (mean +/- SD) was comparable to historical data in normal-weight subjects. Oral
      bioavailability was 79.6% +/- 11.5%. After intravenous administration, plasma
      clearance was 9.6 +/- 2.0 L/h, volume of distribution was 165 +/- 30 L and area
      under the curve was 43.7 +/- 11.8 mg.h/L. Linear regression analysis showed the
      volume of distribution to be better correlated with ideal body weight, lean body
      weight, fat-free mass or height (R(2) = 0.60-0.67, P = 0.001-0.003) than with
      total body weight (R(2) = 0.46, P = 0.015). Whereas mean tissue concentrations in
      small intestine (6.99 +/- 2.34 mg/kg) were twice the concomitant plasma
      concentrations, the concentrations in greater omentum (0.801 +/- 0.168 mg/kg) or
      subcutaneous fat (0.638 +/- 0.180 mg/kg) were only one-quarter of those.
      CONCLUSIONS: The pharmacokinetics of moxifloxacin is not significantly affected
      by morbid obesity. No dose adjustment seems to be necessary in this particular
      population.

PMID- 21729932
TI  - A randomized comparison of caspofungin versus antifungal prophylaxis according to
      investigator policy in acute leukaemia patients undergoing induction chemotherapy
      (PROFIL-C study).
AB  - BACKGROUND: Invasive fungal infections (IFIs) are considered a major problem
      among patients undergoing acute leukaemia (AL) induction treatment. PROphylaxis
      of Fungal invasive Infections in Leukaemia-Caspofungin (PROFIL-C) is a
      multicentre study aiming to assess the comparative yield of using caspofungin
      versus standard policy (SP) regimens and the overall impact of IFI in routine
      clinical care conditions. METHODS: All AL patients receiving IFI prophylaxis
      according to local SP were prospectively included in the study by Northern Italy
      Leukaemia Group (NILG) centres. To allow the comparison of caspofungin versus SP
      regimens as prophylaxis strategies, caspofungin treatment was assigned via a
      centralized randomized procedure. The study was registered at
      http://www.clinicaltrial.gov (NCT00501098). RESULTS: Over a 2 year period, 175
      patients were included. The overall incidence of IFI was 32/175 (18.3%) [10/175
      (5.7%) probable/proven and 22/175 (12.6%) possible], with no statistically
      significant differences between caspofungin-based versus SP-based regimens
      [overall: 15/93 (16.1%) versus 17/82 (20.7%), relative risk (RR) 0.78, 95%
      confidence interval (CI) 0.42-1.46; probable/proven: 7/93 (7.5%) versus 3/82
      (3.7%), RR 2.06, 95% CI 0.55-7.7; possible: 8/93 (8.6%) versus 14/82 (17.1%), RR
      0.5, 95% CI 0.22-1.14]. Only one IFI-related death was recorded (10%).
      CONCLUSIONS: The incidence and mortality of IFI were lower than expected in this
      strictly sequential cohort representative of the routine care in the NILG
      network. The efficacy and safety of caspofungin were similar to other
      prophylactic regimens.

PMID- 21729933
TI  - New horizons for treatment of ANCA-associated vasculitides.

PMID- 21729935
TI  - The publisher has removed this paper.

PMID- 21729934
TI  - Clinical features of childhood localized scleroderma in an incidence cohort.
AB  - OBJECTIVES: Our aim was to describe clinical features and pattern of care in
      children with localized scleroderma presenting to secondary care during a 25
      month incidence study. METHODS: Eighty-seven patients were identified, and
      clinical features, serum autoantibodies, current treatment and outcome at 12
      months were documented. RESULTS: Fifty-eight (67%) had linear scleroderma, 25
      (29%) non-linear morphoea and 4 (4%) a mixed pattern. Of the 58 patients with
      linear scleroderma, 29 (50%) presented with lesions of the trunk and/or limbs
      only, 26 (45%) with face-head localization only and 3 (5%) with both. Thirteen
      (15%) had extracutaneous features and 16 (43%) out of 37 were ANA positive. At 12
      months, 59% were on MTX. At 12 months, 51 (65%) were improved/resolved, 14 (18%)
      were unchanged and 13 (17%) had deteriorated. CONCLUSION: Key findings included
      the high prevalence of face-head involvement in those with linear disease, and
      the high prevalence of extracutaneous disease and of ANA positivity. After 12
      months, most patients improved according to clinician's opinion.

PMID- 21729936
TI  - Justification: how to get referring physicians involved.
AB  - Barriers to involvement of clinicians in the process of justification include an
      already overloaded knowledge base, lack of time, inconsistent guidance and
      disproportionate patient expectations. Strategies to improve referring
      physicians' input include education, use of imaging referral guidelines, clinical
      audit and regulation. This article discusses and reviews evidence for approaches
      to encourage greater participation in justification by clinicians. Approaches are
      best summarised by 'Awareness, appropriateness and audit'.

PMID- 21729937
TI  - AOCRP-3: Achievements and aims.

PMID- 21729938
TI  - Achievements and current activities of the Canadian radon program.
AB  - Based on new scientific information and broad public consultation, the Government
      of Canada updated the guideline for exposure to indoor radon and launched a multi
      year radon program in 2007. Major achievements accomplished in the past 3 y and
      current activities underway are highlighted here.

PMID- 21729939
TI  - Prediction of the variation in risks from exposure to radon at home or at work.
AB  - On the basis of a review of recent epidemiology, the ICRP recently issued a
      statement outlining a new approach to radon. The ICRP indicates that the
      Publication 65 dose conversion convention will be replaced using the dosimetric
      approach currently used for other radionuclides. Moreover, the ICRP indicates
      that the dose conversion factor is expected to increase by about a factor of 2.
      This paper independently examines the risks associated with exposure to radon and
      decay products through estimation of lifetime excess absolute risks per WLM for a
      variety of epidemiological risk projection models and baseline cancer and
      mortality rates. This paper suggests that current ICRP dosimetric models do not
      reflect the effect of smoking and suggest that basic risk estimates and dose
      conversion factors be based on risks to non-smoking populations with recognition
      that lifestyle choices, especially smoking, have a large effect on the risk from
      exposure to radon.

PMID- 21729940
TI  - Radiological emergency: Malaysian preparedness and response.
AB  - Planning and preparation in advance for radiological emergencies can help to
      minimise potential public health and environmental threats if and when an actual
      emergency occurs. During the planning process, emergency response organisations
      think through how they would respond to each type of incident and the resources
      that will be needed. In Malaysia, planning, preparation for and response to
      radiological emergencies involve many parties. In the event of a radiological
      emergency and if it is considered a disaster, the National Security Council, the
      Atomic Energy Licensing Board and the Malaysian Nuclear Agency (Nuclear Malaysia)
      will work together with other federal agencies, state and local governments,
      first responders and international organisations to monitor the situation,
      contain the release, and clean up the contaminated site. Throughout the response,
      these agencies use their protective action guidelines. This paper discusses
      Malaysian preparedness for, and response to, any potential radiological
      emergency.

PMID- 21729941
TI  - Dose evaluation from multiple detector outputs using convex optimisation.
AB  - A dose evaluation using multiple radiation detectors can be improved by the
      convex optimisation method. It enables flexible dose evaluation corresponding to
      the actual radiation energy spectrum. An application to the neutron ambient dose
      equivalent evaluation is investigated using a mixed-gas proportional counter. The
      convex derives the certain neutron ambient dose with certain width corresponding
      to the true neutron energy spectrum. The range of the evaluated dose is
      comparable to the error of conventional neutron dose measurement equipments. An
      application to the neutron individual dose equivalent measurement is also
      investigated. Convexes of particular dosemeter combinations evaluate the
      individual dose equivalent better than the dose evaluation of a single dosemeter.
      The combinations of dosemeters with high orthogonality of their response
      characteristics tend to provide a good suitability for dose evaluation.

PMID- 21729942
TI  - Development of standard evaluation plan for survey and investigation of residual
      radioactivity on site.
AB  - The development of decommissioning technologies, including those for evaluation
      of the radioactivity inventory and the radiation dose, and a site investigation
      plan are needed to ensure safe decommissioning. The residual radioactivity should
      be measured and analysed to release a site for unrestricted use. The methods used
      for measurement of residual radioactivity have an effect on the workers' manpower
      and the decommissioning cost. So the development of the measurement methods of
      residual radioactivity with guidelines for a radiation survey and site
      investigation is needed to prepare for the future decommissioning of commercial
      Nuclear Power plants. The major considerations and characteristics of the
      parameters related to the decision of measurements points have been reviewed. The
      methods for controlling uncertainty and techniques to determine whether the
      measurement results achieve the survey objectives have been established.

PMID- 21729943
TI  - Sperm abnormalities in high- and low-dose-rate Gamma-irradiated Korean dark
      striped field mice, Apodemus agrarius coreae.
AB  - To evaluate the in vivo effects of low-dose-rate (0.7 mGy h(-1)) gamma radiation,
      abnormal shapes of sperm in the caudal epidydimus of Apodemus agrarius coreae (A.
      a. coreae) were used. The six categories of abnormal forms (amorphous heads,
      blunt hooks, excessive hooks, two heads and tails, folded tails and short tails)
      of sperm were observed eight days after gamma irradiation (0, 0.5, 1 and 2 Gy)
      with a high dose rate (0.8 Gy min(-1)) and a low dose rate. The frequency of
      total abnormal sperm gradually increased starting from 0.5 Gy after high-dose
      rate radiation. Blunt hooks and short tails shaped sperm, in particular, were
      gradually increasing in the high-dose-rate irradiated mice. Dose rate reduction
      effects for the frequency of abnormal sperms in low-dose-rate irradiated mice to
      high-dose-rate irradiated mice were 1 at 0.5 Gy, 0.7 at 1 Gy and 0.5 at 2 Gy. Our
      results indicate that low-dose-rate radiation is not detrimental to spermatogenic
      cells.

PMID- 21729944
TI  - Current status of radiological protection at Swiss NPPS.
AB  - Occupational exposure in nuclear power plants has been reduced significantly
      within the last two decades. Dose distribution of workers shows that 80 % have a
      dose <1 mSv y(-1). Discharges have always been low, resulting in hypothetical
      doses of a few micro Sieverts per year to the most affected persons. Dose
      distribution owing to natural and medical exposure does not change for the
      majority of workers by adding their occupational dose distribution. Doses from
      discharges do not have any impact on the dose distribution of the public. Nuclear
      power implicates no additional radiation risks to the public and tiny risks for a
      few of the workers. Nuclear power contributes positively to the environment and
      to public health with tremendous savings of greenhouse gas emissions. Comparing
      the public benefits, tiny doses for workers are easily justified. Further
      reductions of discharge limits or occupational exposure constraints are without a
      real gain in public health.

PMID- 21729945
TI  - Functional expression of a plant hydroxynitrile lyase in Escherichia coli by
      directed evolution: creation and characterization of highly in vivo soluble
      mutants.
AB  - Low protein solubility of recombinantly expressed proteins in Escherichia coli is
      a major factor hindering their application and analysis. We generated highly in
      vivo soluble mutants of a hydroxynitrile lyase in E.coli using protein
      engineering. Structure-guided saturation mutagenesis caused high solubility of
      single Lys-Pro mutations at positions 176, 199 and 224 of this low soluble wild
      type enzyme. The triple Lys-Pro mutant generated at these surface conserved
      residues showed up to 8-fold increase in specific activity in the cell-free
      extract. Random mutagenesis also created a mutant of His103Met with 18.5-fold
      increase. The main expression form was reversed from insoluble to the soluble
      fraction following both types of above-mentioned mutations in E.coli at 37
      degrees C. The findings challenge the rationale of producing recombinant proteins
      in this host at 37 degrees C. Formerly wild type low soluble protein was then
      present as soluble protein by these mutations, which also elevated the total
      soluble protein fraction in E.coli. Saturation mutagenesis of His103 provided
      other highly soluble mutants with hydrophobic substitutions. These mutations
      caused only minor secondary structural changes as determined by circular
      dichroism and Fourier-transform infrared spectroscopy and affected catalytic
      efficiency slightly for the purified mutants (0.82-1.6-fold for benzaldehyde and
      0.9-1.9-fold for mandelonitrile). The stability of the mutants was differed from
      that of the wild type at high temperatures and at pH >8. Exchanging the buried
      basic-polar residue His103 with hydrophobic amino acids is in line with the
      overall structure of the enzyme, i.e. having hydrophilic residues in solvent
      exposed areas and hydrophobic residues in the core.

PMID- 21729946
TI  - Probing the stability-limiting regions of an antibody single-chain variable
      fragment: a molecular dynamics simulation study.
AB  - Antibody single-chain variable fragments (scFvs) offer particular advantages over
      the full-size antibodies, including easy expression, efficient local
      concentration and fast body clearance. However, scFvs typically show low thermal
      stability that limits their biomedical and biotechnological applications. In this
      study, we examined the thermal stability of the human and murine vascular
      endothelial growth factor antibody scFv fragment by molecular dynamics
      simulations. A consistent observation was the dissociation of the light-chain
      (VL) and heavy-chain (VH) domains and loss of the native structures of both
      domains in the simulations at the elevated temperatures. The stability-limiting
      structural elements in the protein were revealed from the detailed analyses on
      the native contacts. We found that dissociation of the VL-VH domains was the
      first event leading to the unfolding of the native structure of the protein and
      the disruption of the VL-VH interface was largely due to the break of the
      interfacial hydrophobic and aromatic interactions while the hydrogen-bonding
      interaction between Gln38 in VL and Gln39 in VH remained. Within the beta-barrel
      structure of the VL and VH domains, beta-strands beta6, beta2 and beta11 appeared
      to be the least stable. In addition, we found that the VH domain was more
      thermally resistant than the VL domain. Based on these findings, we discussed
      potential strategies to improve the stability of this therapeutically important
      scFv fragment.

PMID- 21729947
TI  - Successful treatment of parapneumonic empyema after H1N1 infection in a heart
      transplant recipient.
AB  - Pandemic influenza A H1N1 virus is likely to cause severe disease in patients who
      have received solid organs transplants. In these patients pneumonia is the most
      frequent clinical feature. Parapneumonic empyema (PPE) may represent the
      evolution of secondary bacterial respiratory infections. To our knowledge this is
      the first reported case of PPE during H1N1 influenza A in an adult heart
      transplanted patient. The patient was treated successfully with surgical
      empyemectomy and lung decortication, broad-spectrum antibiotics and oseltamivir.
      Eradication of influenza was obtained in the fifth postoperative day.

PMID- 21729948
TI  - Long-term outcome following repair of acute type A aortic dissection after
      previous cardiac surgery.
AB  - We evaluated the outcome after repair for acute spontaneous type A aortic
      dissection in patients with previous cardiac surgery. From January 2000 to
      December 2009, 114 patients underwent emergency repair for acute spontaneous type
      A dissection at Southampton University Hospital. Eleven (median age 64 years;
      range 36-83 years; two females) patients (9.8%) had undergone previous cardiac
      surgery and were included in this study. Aortic root replacement was performed in
      three patients (27%), aortic arch replacement in four patients (36%) and two
      patients (18%) required aortic valve re-suspension. The elephant trunk operation
      was performed in two patients (18%). There were two hospital deaths (18%). Two
      patients (18%) suffered a stroke, two needed re-opening for bleeding (18%) and
      two patients (18%) required haemofiltration postoperatively. Median length of
      hospital stay was 16 days (range 6-34 days). Actuarial survival at five and eight
      years for redo compared to first-time surgery was 68+/-3.63% vs. 81+/-5.34% and
      51+/-3.8% vs. 61+/-5.4%, respectively (P=0.365). In conclusion, acute type A
      aortic dissection repair in patients with previous cardiac surgery has an
      acceptable mortality and comparable long-term outcome to first-time surgery.

PMID- 21729949
TI  - Postoperative non-invasive assessment of pulmonary vascular resistance using
      Doppler echocardiography.
AB  - Non-invasive monitoring of pulmonary vascular resistance (PVR) in postoperative
      cardiac surgery patients might be useful, particularly for management of
      pulmonary hypertension. For this purpose, we sought to assess Doppler
      echocardiography in the intensive care setting. In 73 patients, hemodynamics was
      measured using both, invasive gold standard (pulmonary artery catheter), and non
      invasively by Doppler echocardiography. Four Doppler parameters: (1) tricuspid
      regurgitant velocity/time-velocity-integral of right ventricular outflow tract
      (TRV/VTI(RVOT)), (2) tricuspid annular systolic velocity (S'), (3) tricuspid
      annular strain, and (4) tricuspid annular strain rate, were compared with
      invasive PVR, using linear regression analysis and receiver-operating
      characteristics. Patients without (n = 25, group 1) and patients with elevated
      left ventricular filling pressure (wedge pressure >= 15 mmHg, group 2, n = 48)
      were compared. Correlations were (1) R = 0.874, P < 0.0001, (2) R = -0.765, P <
      0.0001, (3) R = 0.279, P = 0.009, (4) R = 0.378, P = 0.001. TRV/VTI(RVOT) showed
      prediction of PVR >300 dyn*s*/cm(5) (area-under-curve 0.975, cut-off 0.245,
      sensitivity 100%, specificity 91%). Strain correlated with PVR in group 2
      patients only. TRV/VTI(RVOT) and tricuspid annular systolic velocity (S'), are
      useful for non-invasive monitoring of PVR in postoperative cardiac surgery
      patients with or without elevated left ventricular filling pressure. Strain may
      be used in patients with elevated filling pressure.

PMID- 21729950
TI  - Surgery for aspergilloma: time trend towards improved results?
AB  - Surgery of aspergilloma has been renowned to be technically challenging and has a
      high complication rate. We have already demonstrated an improved outcome as a
      result of a reduction in complex cases related to history of tuberculosis. In
      this paper we will evaluate whether this time trend has continued during recent
      years. Initial presentation and postoperative outcome of 33 patients who
      underwent surgical treatment between 1998 and 2009 were reviewed and compared
      with two previous reports (group 1: 55 patients from 1974 to 1991; group 2: 12
      patients from 1992 to 1997). Underlying disease was tuberculosis in 15% of
      patients (57% in group 1, 17% in group 2), and 12% of patients had complex
      aspergillomas (80% in group 1, 41% in group 2). Postoperatively, there was no
      mortality (5% in group 1, 0% in group 2). Morbidity decreased progressively in
      terms of bleeding (44% in group 1, 9% in group 2, and 6% in recently, accrued
      patients), of pleural space problems (47%, 18% and 12%, respectively), and of
      prolonged hospital stay (32%, 8% and 6%, respectively). With a decreased
      postoperative complications rate after resection, contemporary surgery of
      aspergilloma is safe and offers satisfactory early and long-term results.

PMID- 21729951
TI  - BASHH UK guideline for the management of epididymo-orchitis, 2010.
AB  - The BASHH UK guideline for the management of epididymo-orchitis has been updated
      in 2010. Consideration should be made of the changing potential aetiologies of
      epididymo-orchitis - mumps in non-immune individuals and tuberculosis in the
      immunocompromised and men from countries of high prevalence. The treatment of
      sexually acquired epididymo-orchitis has changed given the high levels of
      quinolone-resistant gonorrhoea such that ceftriaxone and doxycycline are
      recommended in those at high risk of gonorrhoea and doxycycline or ofloxacin in
      those patients where gonorrhoea is considered unlikely (negative microscopy for
      Gram-negative intracellular diplococci and no risk factors for gonorrhoea
      identified). A clinical care pathway has also been produced to simplify the
      management of epididymo-orchitis.

PMID- 21729952
TI  - Using patient experience to measure the quality of HIV care.
AB  - Measurement of health-care quality in the UK is no longer restricted to
      evaluating the effectiveness of treatments or the cost efficiency of services.
      There is a drive towards a patient-based agenda which enables them to make a
      clear contribution to the way services are shaped by expressing their values and
      sharing experiences. Positive engagement with HIV care has proven benefits to
      patients and the mandatory use of standardized reported outcome measures provides
      an opportunity to include HIV patients in the process of creating and refining an
      evaluation tool which places emphasis on aspects of care that are significant to
      them. Ultimately, this will provide services users with a stronger voice to guide
      appropriate service change and support the continuing improvement of HIV care.

PMID- 21729953
TI  - Coverage of highly active antiretroviral therapy among postpartum women in
      Malawi.
AB  - The expanding services of antiretroviral treatment (ART) in sub-Saharan Africa
      provide unique opportunities to reduce HIV/AIDS-related morbidity and mortality.
      In these settings, HIV prevalence among antenatal women remains high and treating
      eligible pregnant or breastfeeding women with antiretrovirals can substantially
      reduce transmission of HIV from the mother to her infant. However, identification
      of women eligible for treatment and ensuring access to ART services is
      challenging. In this analysis, we used data from a large clinical trial (the PEPI
      Malawi study, 2004-09) to prevent mother-to-child transmission of HIV through
      extended antiretroviral prophylaxis of infants to examine barriers for wider
      coverage with highly active antiretroviral treatment (HAART) of postpartum women.
      Maternal HAART was not part of the original PEPI-Malawi clinical trial but became
      available through a government programme during the course of the study.
      Therefore, eligible women (CD4 cell count <250) who participated in the PEPI
      Malawi trial were counselled and referred to the government ART clinics to
      initiate HAART. Of 3335 women who enrolled in the PEPI-Malawi study, 803 (24%)
      were eligible for HAART based on CD4 cell count. The proportion of women newly
      initiating HAART at the ART clinic remained low and constant (<20%) throughout
      the study period. However, the cumulative proportion of women receiving HAART
      increased substantially over time (29% in 2005 to 69% in 2009). Similarly,
      counselling and referral of eligible women substantially increased and became
      100% during the last two years. There were no statistically significant
      differences in characteristics of eligible women who received or did not receive
      HAART postpartum. Despite limitations of not being able to obtain detailed data,
      the main barriers appeared to be related to the health-care system delivery of
      ART services. Issues of physical space, more personnel and better delivery need
      to be addressed to increase access to HAART in these settings.

PMID- 21729954
TI  - Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR Monitor v1.5
      HIV-1 assays on plasma specimens from Rakai, Uganda.
AB  - The need for viral load (VL) monitoring of HIV patients receiving antiretroviral
      therapy (ART) in resource-limited settings (RLS) has become apparent with studies
      showing the limitations of immunological monitoring. We compared the Abbott m2000
      Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1
      assay over a range of VL concentrations. Three hundred and eleven plasma samples
      were tested, including 164 samples from patients on ART >= six months and 147
      from ART-naive patients. The Roche assay detected >=400 copies/mL in 158 (50.8%)
      samples. Of these, Abbott produced 145 (91.8%) detectable results >=400
      copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the
      assays for detecting HIV-1 RNA >=400 copies/mL was 95.8% (298/311). The
      sensitivity, specificity, positive predictive value and negative predictive value
      of Abbott to detect HIV-1 RNA >=400 copies/mL were 91.8%, 100%, 100% and 92.2%,
      respectively. For the 151 samples with HIV-1 RNA >=400 copies/mL for both assays,
      a good linear correlation was found (r = 0.81, P < 0.0001; mean difference,
      0.05). The limits of agreement were -0.97 and 1.07 log(10) copies/mL (mean +/- 2
      SD). The Abbott assay performed well in our setting, offering an alternative
      methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction
      (PCR) capacity.

PMID- 21729955
TI  - Health-seeking behaviour of women selling sex in Lahore, Pakistan.
AB  - The aim of this study was to describe the knowledge and health-seeking behaviour
      related to sexually transmitted infections (STIs) and abortion among women
      selling sex in Lahore, Pakistan. This was a cross-sectional, community-based,
      quantitative study. A total of 730 women selling sex were recruited by respondent
      driven sampling. A pretested structured questionnaire was administered through
      face-to-face interviews. The median age of the participants was 30 years.
      Thirteen percent of the participants said it was common for them to have an
      abnormal vaginal discharge. Seventy-five percent of the participants recognized
      STIs as either leucorrhoea or AIDS. Sixty-five percent of the participants
      complained of having suffered from STI(s) in the six months preceding the survey,
      of whom 28% sought treatment. Women selling sex who reported consistent condom
      use were 1.5 times (95% confidence interval [CI]: 1.1-2.2) more likely to seek
      treatment than women who did not report consistent condom use. The level of
      knowledge about STIs remains low among women selling sex in Lahore, Pakistan, and
      health-seeking behaviour for the management of STIs and abortions is influenced
      by ability to pay and ease of access in the private sector.

PMID- 21729956
TI  - Knowledge of sexually transmissible infections: a comparison of prisoners and the
      general population.
AB  - The World Health Organization (WHO) has identified a failure to provide education
      for vulnerable populations such as prisoners as a contributing factor to the
      epidemic of sexually transmissible infections (STIs). Despite this recognition,
      little is known about prisoners' level of knowledge of STIs compared with the
      general population. Using computer-assisted telephone interviews, we compared a
      representative sample of 2289 Australian prisoners, aged 18-59 years from New
      South Wales and Queensland prisons with a representative community sample of 3536
      participants from these two states. Prisoners had significantly better knowledge
      than the general community of chlamydia-related questions, while knowledge of
      herpes (genital and oral) was slightly better in the community sample. Prisoners
      who were aged over 25 years, not married, female, self-identified as either
      homosexual or bisexual and reported a history of STIs tended to have better STI
      knowledge levels. Despite their more disadvantaged backgrounds, prisoners
      demonstrated relatively good health literacy in relation to STIs. Ongoing
      education about the transmission risks of STIs for prisoners and the general
      community is needed.

PMID- 21729957
TI  - Seroprevalence of herpes simplex virus 2 among Hispanics in the USA: National
      Health and Nutrition Examination Survey, 2007-2008.
AB  - To examine the seroprevalence of herpes simplex virus type 2 (HSV-2) among
      Hispanics in the USA, we used the cross-sectional, nationally representative
      National Health and Nutrition Examination Survey to compare the seroprevalence of
      HSV-2 between Hispanic persons of Mexican heritage and non-Mexican heritage aged
      14-44 years, from survey years 2007-2008. The overall HSV-2 seroprevalence among
      Hispanics aged 14-44 years was 17.5% (95% confidence interval [CI], 15.2, 20.1)
      in the USA. HSV-2 seroprevalence was significantly lower among Mexican Americans
      than among other Hispanics (11.7% vs. 27.8%, P < 0.01). Prevalence of HSV-2 was
      also significantly associated with gender and age. The significant difference in
      HSV-2 seroprevalence between Hispanic persons of Mexican heritage and non-Mexican
      heritage suggested that targeting specific subgroups of Hispanics for preventive
      interventions may be a strategy to reduce the transmission of HSV-2 and HIV among
      Hispanics in the USA.

PMID- 21729958
TI  - Determinants of condom use among HIV-positive men who have sex with men.
AB  - The main objectives of this study were to identify the determinants of condom use
      among HIV-positive men having anal sex with HIV-negative men or men of unknown
      HIV status and moderators of the intention-behaviour relationship. A cohort of
      237 sexually active HIV-positive men having sex with men was followed over a
      period of six months. The cognitive variables measured were guided by an extended
      version of the theory of planned behaviour. Results indicated that past behaviour
      (odds ratio [OR] = 9.75; 95% confidence interval [CI]: 4.48-21.26), intention (OR
      = 3.13; 95% CI: 1.25-7.81), self-efficacy (OR = 3.62; 95% CI: 1.40-9.37) and use
      of sex drugs (OR = 0.16; 95% CI: 0.06-0.45) contributed to the prediction of 100%
      condom use. Self-efficacy also interacted with intention as a significant
      moderator of the intention-behaviour relationship (OR = 20.96; 95% CI: 2.90
      151.51). Interventions promoting condom use should increase self-efficacy to use
      condoms and target users of sex drugs.

PMID- 21729959
TI  - Positive nucleic acid amplification tests for Neisseria gonorrhoeae in young
      people tested as part of the National Chlamydia Screening Programme.
AB  - Little information is available on the prevalence of Neisseria gonorrhoeae (GC)
      infections outside genitourinary (GU) medicine clinics. A number of National
      Chlamydia Screening Programme areas now carry out simultaneous testing for
      Chlamydia trachomatis (CT) and GC in a single sample using nucleic acid
      amplification tests (NAATs). The aim of this study was to gather together data on
      dual testing from community settings. Information was collected from five
      programme areas. A total of 219,412 results were recorded with 18,370 CT
      positives, 1226 GC positives and among these 554 were with dual CT/GC infection.
      These figures highlight the fact that substantial numbers of positive GC NAAT
      results are found outside GU settings. An assessment of both the prevalence of GC
      and the proportion of extra cases that can be detected in all settings is needed,
      together with the implementation of robust plans to confirm, treat and manage
      these patients.

PMID- 21729960
TI  - Human papillomavirus vaccination uptake and factors related to uptake in a
      traditional desert city in the United Arab Emirates.
AB  - It is important to assess uptake of a new vaccine. The present survey estimated
      the uptake of the recently introduced human papillomavirus vaccine (HPVV) in the
      emirate of Abu Dhabi and also explored barriers to uptake. A questionnaire survey
      was conducted in secondary schools, enrolling 334 girls. The uptake percentage
      was estimated and factors associated with uptake were assessed with multilevel
      logistic regression. Crude vaccination uptake was 53%. Factors positively
      associated with uptake were, among others, having knowledge on human
      papillomavirus (vaccine) and having United Arab Emirates (UAE) nationality. The
      HPVV uptake of just over 50% could probably be improved by educating the target
      group and their parents before offering the HPVV and by making it free of costs
      for everyone.

PMID- 21729961
TI  - Vaccination against hepatitis B in an HIV outpatients' department: an audit
      against national vaccination guidelines.
AB  - Practice related to hepatitis B vaccination of HIV outpatients in a London
      teaching hospital was audited against the British HIV Association (BHIVA)
      immunization guidelines 2004 and 2008, both before and after the implementation
      of a vaccination record sheet in the patients' notes. Adherence to the guidelines
      in the original audit was poor - only 67% of patients requiring vaccination for
      hepatitis B received a full course of vaccination. Following the introduction of
      the vaccination record sheet, this vaccination completion rate increased to 79%
      (BHIVA target 95%). Overall the percentage of patients managed according to BHIVA
      guidelines, including those who did not require vaccination, improved from 33% in
      the original audit to 61% in the re-audit. Introduction of a simple hepatitis B
      vaccination record sheet improved the quality of care for our HIV outpatients.
      Further modification of this system is warranted, perhaps by the introduction of
      a computerized reminder system.

PMID- 21729962
TI  - Post-exposure prophylaxis following sexual exposure to HIV: a seven-year
      retrospective analysis in a regional centre.
AB  - An audit of 72 patients presenting for post-exposure prophylaxis following sexual
      exposure (PEPSE) to HIV (68 genitourinary medicine and 4 accident & emergency)
      was conducted from 2003 to 2009. The principal indications for PEPSE included 27
      (38%) unprotected intercourse (15/27 vaginal and 12/27 anal) with a known HIV
      positive partner, 20 (28%) unprotected receptive anal sex with male partner of
      unknown status, 17 (24%) following sexual assault and three (4%) unprotected sex
      with a partner from an endemic country. Of those who commenced PEPSE, 92% did so
      within the recommended 72 hours. Concurrent sexually transmitted infection (STI)
      was diagnosed in 8.3% patients (6.9% non-gonococcal urethritis and 1.4% rectal
      chlamydia). Fifty (69%) patients attended for follow-up and only 8% of these did
      not complete treatment. Twenty-five (35%) patients attended for repeat serology
      at three months and 18 (25%) at six months. All of the patients followed up
      remained HIV-negative.

PMID- 21729963
TI  - Complete regression of early diffuse B-cell lymphoma in an HIV-positive patient
      on antiretroviral therapy alone.
AB  - There is no evidence that antiretroviral therapy (ART) alone may result in
      complete remission of aggressive non-Hodgkin's lymphomas even though it improves
      the overall prognosis. We report a case in which early diffuse large B-cell
      lymphoma regressed completely after ART alone, raising the possibility that this
      may be sufficient therapy in selected cases.

PMID- 21729964
TI  - Trimethoprim-sulphamethoxazole-associated rhabdomyolysis in an HIV-infected
      patient.
AB  - We describe a case of rhabdomyolysis associated with trimethoprim
      sulphamethoxazole (TMP-SMZ) in a HIV-infected patient. A 33-year-old African
      American man with newly diagnosed AIDS initially presented with persistent, high
      grade fevers suspected to be TMP-SMZ-related drug fever. The antibiotic was
      discontinued while in the hospital, but the patient was restarted on TMP-SMZ
      following discharge. Two days later, he returned to the hospital with severe
      muscle pain, acute renal failure and a significantly elevated creatine
      phosphokinase consistent with rhabdomyolysis. The patient gradually improved
      following discontinuation of TMP-SMZ.

PMID- 21729965
TI  - Implanon(r) failure in an HIV-positive woman on antiretroviral therapy resulting
      in two ectopic pregnancies.
AB  - Since its introduction in 1999, Implanon(r) remains one of the preferred
      contraceptive choices for many women as it offers a highly effective means of
      long-term contraception for three years that does not rely on adherence. Like all
      hormonal contraceptives, certain hepatic enzyme-inducing drugs may reduce its
      efficacy. We present an interesting case of an HIV-positive woman on
      antiretroviral therapy having tubal pregnancies on two separate occasions with
      Implanon in place.

PMID- 21729966
TI  - 'How to contain generalized HIV epidemics' article misconstrues the evidence.

PMID- 21729967
TI  - Sexual health in prisons.

PMID- 21729969
TI  - The utility of a diagnostic skin biopsy clinic within the genitourinary medicine
      clinic.

PMID- 21729970
TI  - Male genital skin biopsy.

PMID- 21729972
TI  - Response to Tipple et al: is screening for pharyngeal Chlamydia trachomatis
      warranted in high-risk groups?

PMID- 21729973
TI  - Listening to the heart-brain talk: persistent depressive symptoms are associated
      with hsCRP in apparently healthy individuals at high risk for coronary artery
      disease.
AB  - BACKGROUND: This study examined whether mild-to-moderate depressive symptoms are
      associated with increased high-sensitivity C-reactive protein (hsCRP) and
      interleukin 6 (IL-6) levels in apparently healthy individuals at high risk for
      coronary artery disease. We investigated in individuals whether: (1) current
      depressive symptoms were associated with increased hsCRP and IL-6 levels; (2)
      persistent depressive symptoms at two time points 6 months apart were associated
      with hsCRP and IL-6; and (3), sex-based differences in inflammation were a
      function of depressive symptoms. METHODS: We measured depressive symptoms
      (twice), hsCRP, and IL-6 (follow-up time point) in 84 apparently healthy
      individuals (52% women) at high cardiac risk. RESULTS: Patients with persistent
      depressive symptoms had higher hsCRP, compared to participants without persistent
      symptoms (5.55 vs. 1.70 mg/l, p < 0.05, 95% CI 0.11 to 1.09, d = 0.67).
      Participants with current depressive symptoms had higher hsCRP (3.99 vs. 1.70
      mg/l, p = 0.059) than those without symptoms. Findings remained unchanged after
      controlling for covariates. Women had higher adjusted hsCRP than men (2.91 vs.
      1.87 mg/l, p < 0.001). When we entered depressive symptoms, the model remained
      significant, with a significant interaction between sex and symptoms: women with
      depressive symptoms had higher hsCRP than men with depressive symptoms and than
      women without symptoms (6.75 vs. 1.11 mg/l). The hypothesized differences were
      not observed with respect to IL-6, after controlling for body mass index (95% CI
      0.77 to 0.73). CONCLUSIONS: Before a first ischaemic coronary event, persistent
      mild-to-moderate depressive symptoms were associated with increased hsCRP. Women
      with depressive symptoms had higher hsCRP than men with symptoms.

PMID- 21729974
TI  - Casting, taping or stretching after botulinum toxin type A for spastic equinus
      foot: a single-blind randomized trial on adult stroke patients.
AB  - OBJECTIVE: To investigate the effect of different adjunctive treatments after
      botulinum toxin type A. DESIGN: Single-blind, randomized trial, with three-month
      follow-up. SETTING: Secondary rehabilitative care. SUBJECTS: Convenience sample
      of 69 chronic hemiplegic adult patients with spastic equinus foot. INTERVENTIONS:
      Following botulinum toxin type A injection at the plantar flexors, patients were
      randomly assigned to three groups and treated with either taping, casting or
      stretching for one week, and with stretching and gait training for the next week.
      OUTCOME MEASURES: Modified Ashworth Scale at plantar flexors, passive range of
      motion at the ankle, six-minute walking test, 10-metre walking test, Functional
      Ambulation Categories, ankle dorsiflexor strength were evaluated before treatment
      (t(0)) at 20 days (t(1)) and 90 days (t(2)) after treatment. RESULTS: At t(1)
      only the taping and casting groups showed significant improvements in Modified
      Ashworth Scale, six-minute walking test, 10-metre walking test and passive range
      of motion (P < 0.02). At t(2), while the results were maintained in the casting
      group, only six-minute walking test and Modified Ashworth Scale were still
      significantly improved in the taping group. Ankle dorsiflexor strength and
      Functional Ambulation Categories did not change in any of the groups at any time.
      At t(2) the casting group performed better than the taping and stretching groups
      at Modified Ashworth Scale and passive range of motion, and better than the
      stretching group at six-minute walking test (P < 0.02). CONCLUSIONS: Combining
      botulinum toxin type A to the ankle plantar flexors with casting or taping gives
      better and longer lasting results than with stretching alone.

PMID- 21729975
TI  - Dysarthria following stroke: the patient's perspective on management and
      rehabilitation.
AB  - OBJECTIVE: To explore the perceptions of people with stroke-related dysarthria in
      relation to the management and rehabilitation of dysarthria. DESIGN: Qualitative
      semi-structured interviews. SETTING: Community setting Subjects: Twenty-four
      people with an acquired dysarthria as a result of a stroke in the previous three
      years. All were living at home at the time of the interview. None exhibited a co
      existing impairment (for example, aphasia, apraxia or cognitive impairment) that
      might have contributed to their communicative experiences. RESULTS: Participants
      described the considerable efforts they made to maximize their communicative
      effectiveness prior to, and during, communicative interactions. Activities
      described included careful articulation and vocal projection as well as more
      inconspicuous strategies including pre-planning interactions, focused, effortful
      speech and word substitution. Communication was facilitated by a range of
      strategies including drafting, rehearsal, manoeuvring and ongoing monitoring and
      repair. Self-led speech rehabilitation activities were functionally based and
      often undertaken regularly. Some novel reading-aloud and speaking-aloud
      activities were described. CONCLUSION: The quantity and nature of inconspicuous,
      internalized, cognitive activities people with dysarthria engage in to maximize
      their communicative effectiveness should be considered in evaluating the impact
      of dysarthria following stroke. Focusing upon externally observable
      characteristics alone is insufficient. Challenging, functionally relevant,
      patient-focused activities, materials and targets are more likely to be perceived
      by the patient as relevant and worthwhile and are thus more likely to ensure
      adherence to recommended rehabilitation activities.

PMID- 21729976
TI  - Neurotoxicity of cobalt.
AB  - Cobalt exerts well-known and documented toxic effects on the thyroid, heart and
      the haematopoietic system, in addition to the occupational lung disease, allergic
      manifestations and a probably carcinogenic action. Cobalt neurotoxicity is
      reported in isolated cases, and it has never been systematically treated.
      Bilateral optic atrophy and retinopathy, bilateral nerve deafness and sensory
      motor polyneuropathy have been described long ago as a result of chronic
      occupational exposure to cobal powder or during long-term treatment of anaemia
      with cobalt chloride. Recently, some patients with high levels of cobalt released
      from metal prosthesis have been referred as presenting with tinnitus, deafness,
      vertigo, visual changes, optic atrophy, tremor and peripheral neuropathy. The aim
      of this work is to group these cases and to identify a possible mechanism of
      cobalt neurotoxicity, focusing on hypothetic individual susceptibility such as
      altered metal-binding proteins, altered transport processes in target cells or
      polymorphic variation of genetic background.

PMID- 21729977
TI  - Antiphospholipid antibodies in patients with purported 'chronic Lyme disease'.
AB  - BACKGROUND: Antiphospholipid antibody (aPL) positive patients and patients with
      purported chronic Lyme disease ('CLD') share many clinical features. After
      identifying significant aPL in sera of several index patients with 'CLD', we
      performed aPL tests on all patients referred in whom 'CLD' was suspected,
      diagnosed or treated. METHODS: All patients with suspected, diagnosed or treated
      'CLD' and reportedly 'positive' Lyme assays were studied. aPL testing included
      anticardiolipin antibodies (aCL), anti-beta-2-glycoprotein-1 antibodies (anti
      beta2GP1) and lupus anticoagulant (LAC). Patients were classified into four newly
      described categories of CLD and data was analyzed. RESULTS: One hundred and six
      patients were evaluated, of whom 82% had neurologic symptoms and 51%
      rheumatologic symptoms. Eighty-eight of 106 (83%) patients had positive Lyme
      serologies (enzyme-linked immunosorbent assay [ELISA] 62/106, 58.4%; western blot
      [WB] 64/106, 60%), while 18/106 (16.9%) were negative or equivocal. aPL was found
      in all 'CLD' categories. aCL and/or anti-beta2GP1 were positive in 85/106 (80%),
      with aCL present in 69/106 (65%) and anti-beta2GP1 present in 69/106 (65%). For
      all assays, IgM isotypes predominated: WB 55/64 (85%), aCL 63/69 (91%), anti
      beta2GP1 52/69 (75%), aCL and/or anti-beta2GP1 74/85 (87%). Anti-beta2GP1 assays
      occurred in higher titer than aCL: 36/69 (52%) versus 63/69 (91%), p<0.001.
      Seventeen patients had aPL-related events. Only 12/106 (11.3%) had true post-Lyme
      syndromes (PLS), category IV, or late Lyme disease (LLD). Most patients had been
      treated for Lyme: 82/106 (79%). CONCLUSION: aPL occurs frequently in patients
      with 'CLD'. IgM anti-beta2GP1, IgM aCL and IgM WB were frequently found.
      Documented PLS or LLD was uncommon. The role of aPL in patients with 'CLD' needs
      further investigation.

PMID- 21729978
TI  - Pronounced focal and diffuse brain damage predicts short-term disease evolution
      in patients with clinically isolated syndrome suggestive of multiple sclerosis.
AB  - BACKGROUND: In clinically isolated syndrome (CIS), the role of quantitative
      magnetic resonance imaging (MRI) in detecting prognostic markers is still
      debated. OBJECTIVE: To evaluate measures of diffuse brain damage (such as brain
      atrophy and the ratio of N-acetylaspartate to creatine (NAA/Cr)) in patients with
      CIS, in addition to focal lesions, as predictors of 1-year disease evolution.
      METHODS: 49 patients with CIS underwent MRI scans to quantify T2-lesions (T2-L)
      and gadolinium-enhanced lesion (GEL) number at baseline and after 1 year. Along
      with 25 healthy volunteers, they also underwent combined MRI/magnetic resonance
      spectroscopy examination to measure normalized brain volumes (NBVs) and NAA/Cr.
      Occurrence of relapses and new T2-L was recorded over 1 year to assess disease
      evolution. RESULTS: Occurrence of relapses and/or new T2-L over 1 year divided
      patients with CIS into 'active' and 'stable' groups. Active patients had lower
      baseline NAA/Cr and NBV. Baseline T2-L number, GEL, NAA/Cr and NBV predicted
      subsequent disease activity. Multivariable logistic regression models showed that
      both 'focal damage' (based on T2-L number and GEL) and 'diffuse damage' (based on
      NBV and NAA/Cr) models predicted disease activity at 1 year with great
      sensitivity, specificity and accuracy. This was best when the four MRI measures
      were combined (80% sensitivity, 89% specificity, 83% accuracy). CONCLUSIONS:
      Quantitative MRI measures of diffuse tissue damage such as brain atrophy and
      NAA/Cr, in addition to measures of focal demyelinating lesions, may predict short
      term disease evolution in patients with CIS, particularly when used in
      combination. If confirmed in larger studies, these findings may have important
      clinical and therapeutic implications.

PMID- 21729979
TI  - Contact dermatitis induced by glatiramer acetate.
AB  - Glatiramer acetate (Copaxone((r))) is an immunomodulatory polypeptide used in
      patients with relapsing-remitting multiple sclerosis. It represents a safe
      treatment option with mild side effects. In this study, we look at a 39-year-old
      woman who received glatiramer acetate as subcutaneous injections for two months
      and developed contact dermatitis. The drug had to be stopped, and treatment with
      topical prednisone was initiated. Prick/scratch testing was negative but the
      lymphocyte transformation test was highly positive for glatiramer acetate. This
      is the first report on contact dermatitis induced by glatiramer acetate
      injections. The treatment consisted of local topical steroids and cessation of
      the drug.

PMID- 21729980
TI  - What did Doppler monitoring study show?

PMID- 21729981
TI  - Outcomes not justified by data.

PMID- 21729982
TI  - Savings? What savings?

PMID- 21729983
TI  - UK drug regulator destroys all evidence after 15 years.

PMID- 21729984
TI  - Phenazepam is currently being misused in the UK.

PMID- 21729985
TI  - Rebuttal to editorial saying cancer survival statistics are misleading.

PMID- 21729986
TI  - Missed opportunity to advance debate on assisted dying.

PMID- 21729987
TI  - Call for an evidence based debate on assisted dying.

PMID- 21729988
TI  - FDA committee votes to withdraw bevacizumab for breast cancer.

PMID- 21729989
TI  - Late abortion statistics are published after pro-life group wins court ruling.

PMID- 21729990
TI  - Senators question Medtronic about unreported side effects of spinal protein.

PMID- 21729991
TI  - The long-term antiproteinuric effect of eplerenone, a selective aldosterone
      blocker, in patients with non-diabetic chronic kidney disease.
AB  - INTRODUCTION: There is still insufficient data concerning the clinical effects of
      eplerenone, a selective aldosterone blocker, in patients with non-diabetic
      chronic kidney disease (CKD). METHODS: This study included non-diabetic CKD
      patients with urinary protein excretion (UPE) of 1.0 g/gCr or more in spite of
      long-term treatment with renin-angiotensin system (RAS) inhibitors. The clinical
      effects of eplerenone (25-50 mg/day) were investigated for 12 months. RESULTS:
      Eplerenone treatment was associated with a 38% reduction in UPE after 12 months.
      There was only a slight increase in the serum potassium level. The reduction of
      proteinuria was observed more prominently in patients with modestly impaired
      renal function than in those with preserved renal function at baseline.
      CONCLUSION: The long-term administration of low-dose eplerenone was effective and
      safe for the treatment of non-diabetic CKD patients who showed persistent
      proteinuria in spite of therapy with RAS inhibitors.

PMID- 21729992
TI  - Physiological regulation of extracellular matrix collagen and elastin in the
      arterial wall of rats by noradrenergic tone and angiotensin II.
AB  - The interactions between the effects of the sympathetic nervous system (SNS) and
      angiotensin II (ANG II) on vascular extracellular matrix (ECM) synthesis were
      determined in rats. The mRNA and protein content of collagen I, collagen III and
      elastin in the abdominal aorta (AA) and femoral artery (FA) was investigated in
      Wistar-Kyoto rats treated for 5 weeks with guanethidine, a sympathoplegic,
      losartan, an ANG II AT1 receptor (AT1R) blocker, or both. The effects of
      noradrenaline (NE) and ANG II on collagen III and elastin mRNA, and the receptor
      involved, were tested in cultured vascular smooth muscle cells (VSMCs) in vitro.
      Guanethidine increased collagen types I and III and decreased elastin, while
      losartan had an opposite effect, although without effect on collagen III. The
      combination of treatments abrogated changes induced by simple treatment with
      collagen I and elastin, but increased collagen III mRNA in AA and not in FA. NE
      stimulated collagen III mRNA via beta receptors and elastin via alpha1 and alpha2
      receptors. ANG II stimulated collagen III but inhibited elastin mRNA via AT1R.
      Overall, SNS and ANG II exert opposite and antagonistic effects on major
      components of ECM in the vascular wall. This may be of relevance for the choice
      of a therapeutic strategy in vascular diseases.

PMID- 21729993
TI  - Improvement of cognitive impairment in female type 2 diabetes mellitus mice by
      spironolactone.
AB  - Patients with type 2 diabetes mellitus (T2DM) exhibit more severe cognitive
      decline in females compared with males; however, the preventive approach to this
      gender-specific cognitive decline is still an enigma. Spironolactone is a
      potassium-sparing diuretic that also acts as an androgen receptor antagonist.
      Here, we investigated whether spironolactone attenuates cognitive impairment
      observed in female T2DM mice. Adult wild-type (WT) mice and an obese T2DM model,
      KKAy mice, were employed in this study. Cognitive function was evaluated by the
      shuttle avoidance test and Morris water maze test. Administration of
      spironolactone (50 mg/kg per day in chow) had no significant effect on blood
      pressure, glucose tolerance or insulin resistance. In WT mice, no significant sex
      difference in cognitive function was observed; however, treatment with
      spironolactone improved spatial memory in the water maze, especially in female WT
      mice. Administration of spironolactone markedly improved the cognitive decline in
      female KKAy mice up to the level in male KKAy mice. Spironolactone treatment also
      improved cognitive function in ovariectomized-KKAy mice, but failed to improve it
      in those with administration of estradiol (200 ug/kg per day). In diabetic mice,
      spironolactone improved impaired cognitive function observed in female mice,
      suggesting that spironolactone may prevent cognitive impairment associated with
      diabetes in females clinically.

PMID- 21729994
TI  - Association between provision of mental illness beds and rate of involuntary
      admissions in the NHS in England 1988-2008: ecological study.
AB  - OBJECTIVE: To examine the rise in the rate of involuntary admissions for mental
      illness in England that has occurred as community alternatives to hospital
      admission have been introduced. DESIGN: Ecological analysis. SETTING: England,
      1988-2008. DATA SOURCE: Publicly available data on provision of beds for people
      with mental illness in the National Health Service from Hospital Activity
      Statistics and involuntary admission rates from the NHS Information Centre. MAIN
      OUTCOME MEASURES: Association between annual changes in provision of mental
      illness beds in the NHS and involuntary admission rates, using cross correlation.
      Partial correlation coefficients were calculated and regression analysis carried
      out for the time lag (interval) over which the largest association between these
      variables was identified. RESULTS: The rate of involuntary admissions per annum
      in the NHS increased by more than 60%, whereas the provision of mental illness
      beds decreased by more than 60% over the same period; these changes seemed to be
      synchronous. The strongest association between these variables was observed when
      a time lag of one year was introduced, with bed reductions preceding increases in
      involuntary admissions (cross correlation -0.60, 95% confidence interval -1.06 to
      -0.15). This association increased in magnitude when analyses were restricted to
      civil (non-forensic) involuntary admissions and non-secure mental illness beds.
      CONCLUSION: The annual reduction in provision of mental illness beds was
      associated with the rate of involuntary admissions over the short to medium term,
      with the closure of two mental illness beds leading to one additional involuntary
      admission in the subsequent year. This study provides a method for predicting
      rates of involuntary admissions and what may happen in the future if bed closures
      continue.

PMID- 21729995
TI  - Is there evidence that competition in healthcare is a good thing? Yes.

PMID- 21729996
TI  - Is there evidence that competition in healthcare is a good thing? No.

PMID- 21729997
TI  - Putting research into primary care practice.

PMID- 21729998
TI  - Disease trackers.

PMID- 21729999
TI  - Study finds almost half of Spanish children are overweight or obese.

PMID- 21730000
TI  - Infertile couples favour Spain and Czech Republic for treatment because of good
      supply of donor gametes, study shows.

PMID- 21730001
TI  - Review of funding for social care in England.

PMID- 21730002
TI  - Individuals' contributions to cost of social care in England should be capped,
      review says.

PMID- 21730003
TI  - Tobacco companies launch legal action against plain packaging.

PMID- 21730004
TI  - Targeted therapy of non-small-cell lung carcinoma.
AB  - The rapid expansion of novel technologies in cancer research over the past
      several years has led to a dramatically improved understanding of the molecular
      biology of lung cancer. As a consequence, novel targeted therapies are rapidly
      being developed. In this review, we summarize the most important molecular
      pathways in lung cancer and describe the clinical evidence for the development of
      therapies against these targets.

PMID- 21730005
TI  - Intravascular papillary endothelial hyperplasia (Masson's tumour) of the finger
      presenting as a digital nerve schwannoma.

PMID- 21730006
TI  - Re: Ozcelik B, Egemen O, Sacak B. How to prevent the avulsed soft tissues from
      wrapping around the K-wire. J Hand Surg Eur. 2011, 36: 518-519.

PMID- 21730007
TI  - The relative importance of systolic versus diastolic blood pressure control and
      incident symptomatic peripheral artery disease in women.
AB  - Prospective data regarding risk factors for peripheral artery disease (PAD) are
      sparse, especially among women; the relative contribution of systolic versus
      diastolic blood pressure control for incident PAD has not been well studied. We
      evaluated the association of self-reported blood pressure control with incident
      symptomatic PAD in middle-aged and older women. We examined the relationship
      between reported hypertension and incident confirmed symptomatic PAD (n = 178) in
      39,260 female health professionals aged >= 45 years without known vascular
      disease at baseline. Median follow-up was 13.3 years. Women were grouped
      according to presence of reported isolated diastolic (IDH), isolated systolic
      (ISH), or combined systolic-diastolic hypertension (SDH) using cut-points of 90
      and 140 mmHg for diastolic and systolic blood pressure, respectively. SBP and DBP
      were modeled as continuous and categorical exposures. Multivariable-adjusted
      hazard ratios (HRs), including adjustment for cardiovascular risk factors, were
      derived from Cox proportional hazards models. Adjusted HRs compared to women
      without reported hypertension were 1.0 (0.4-2.8) for IDH, 2.0 (1.3-3.1) for ISH,
      and 2.8 (1.8-4.5) for SDH. There was a 43% increased adjusted risk per 10 mmHg of
      reported SBP (95% CI 27-62%) and a gradient in risk according to SBP category (<
      120, 120-139, 140-159, and >= 160 mmHg); HRs were 1.0, 2.3, 4.3, and 6.6 (p-trend
      < 0.001), respectively. Reported DBP, while individually predictive in models
      excluding SBP, was not predictive after adjustment for SBP. In conclusion, these
      prospective data suggest a strong prognostic role for uncontrolled blood pressure
      and, particularly, uncontrolled systolic blood pressure in the development of
      peripheral atherosclerosis in women.

PMID- 21730008
TI  - Trends in socioeconomic disparities in the utilization of dental care in Brazil
      and Sweden.
AB  - AIMS: To describe trends in socioeconomic disparities in utilization of dental
      care. METHODS: We obtained cross-sectional data from Sweden in the period 1968
      2000 and from Brazil in 1986 and 2002 for 16 state capitals. The outcome was the
      percentage of people who reported that they had visited the dentist in the last
      12 months, calculated for a higher and a lower income group and stratified by
      sex, age (two groups: young and adults) and dental status. Adjusted prevalence
      differences and prevalence ratios were produced using Poisson regression.
      RESULTS: In Brazil, there was a decline in use of dental care among the 15-19
      year olds in the period 1986-2002, but not among the 35-44 year olds. In Sweden,
      there was a decline among the young and adults between 1991 and 2000. Overall,
      socioeconomic disparities in use of dental services between the higher and the
      lower economic groups showed a decline in both countries. The reduction in
      disparities among young Brazilians was 1.1 percentage points per year (p < 0.01),
      but among the other age groups the decline was not significant (p>0.01). In the
      last surveys, the gap remained in both countries and age groups (p < 0.01).
      CONCLUSIONS: The recent decline in utilization of dental care and in the
      socioeconomic gap may mirror improvements in oral health. However, there are
      still relevant and persistent disparities in utilization of dental care in both
      countries, with a higher proportion of people of higher socioeconomic status
      visiting the dentist.

PMID- 21730009
TI  - The paradox of public health genomics: definition and diagnosis of familial
      hypercholesterolaemia in three European countries.
AB  - AIMS: Considerable progress in public health is expected to occur from the
      application of genomic knowledge and technologies. This is the subject of a newly
      emerging field of public health genomics. In this paper we analyze differences in
      how public health genomics is developing in the Netherlands, the UK and Germany
      through the definition and diagnosis of familial hypercholesterolaemia (FH), an
      inherited predisposition for coronary heart disease. METHODS: We analyzed the
      emergence of public health genomics within the framework of a project on the
      incorporation of genetics in western European healthcare schemes. Our analysis is
      based on document analysis and in-depth interviews. RESULTS: In the Netherlands,
      public health genomics takes shape through a genetic screening programme for FH,
      looking for mutations on two specific genes; in the UK it emerges through a
      strategy of ''mainstreaming'' genetics in health care that aims to identify
      hereditary predispositions by means of phenotypic diagnosis; and in Germany
      public health genomics is elaborated at a conceptual level, leaving a diagnosis
      of FH to individual physicians who occasionally prescribe genetic testing.
      CONCLUSIONS: Our analysis shows how public health genomics gets constituted
      differently in different countries and, moreover, produces particular patterns of
      inclusion and exclusion from care. These patterns indicate a paradox in public
      health genomics, which consists of an inverse relationship between the use of
      advanced molecular genetic testing technologies and the number and variety of
      individuals at risk included in the target population. This paradox presents a
      challenge for professionals and policy makers in public health genomics.

PMID- 21730010
TI  - Distinct effects of imperatorin on allergic rhinitis: imperatorin inhibits
      caspase-1 activity in vivo and in vitro.
AB  - Because imperatorin (IPT), the furanocoumarins exhibits anti-inflammatory
      activity, we reasoned that IPT might modulate the allergic rhinitis (AR). The aim
      of this study was to analyze the regulation of AR by IPT. Here, we show the
      effect and mechanism of IPT in an ovalbumin (OVA)-induced AR model. The number of
      rubs after the OVA challenge in the OVA-sensitized mice was significantly higher
      than that in the OVA-unsensitized mice. The increased number of rubs was
      inhibited by the oral administration of IPT. The increased levels of IgE and
      histamine in the OVA-sensitized mice were reduced by IPT administration. The
      levels of interferon-gamma were enhanced, whereas the levels of interleukin (IL)
      4 were reduced on the spleen tissue of the IPT-administered AR mice. Protein
      levels of IL-1beta, macrophage inflammatory protein-2, intercellular adhesion
      molecule-1, and cyclooxygenase-2 were reduced by IPT administration in the nasal
      mucosa of the OVA-sensitized mice. In the IPT-administered mice, the number of
      eosinophils and mast cells infiltration increased by OVA-sensitization were also
      decreased. In addition, IPT inhibited caspase-1 activity in the same nasal mucosa
      tissue. In activated human mast cells, the receptor-interacting protein 2 (RIP2),
      IkappaB kinase (IKK)-beta, nuclear factor-kappaB (NF-kappaB)/RelA, and caspase-1
      activation were increased, but increased RIP2, IKK-beta, NF-kappaB/RelA, and
      caspase-1 activation were inhibited by the treatment of IPT. In addition, IPT
      inhibited caspase-1 activity and IL-1beta production in IgE-stimulated bone
      marrow-derived mast cells. We can conclude that IPT exerts significant effects by
      regulating of caspase-1 activation in AR animal and in vitro models.

PMID- 21730011
TI  - Patterns of nicotinic receptor antagonism: nicotine discrimination studies.
AB  - Evaluation of the discriminative stimulus effects of drugs is a useful procedure
      for identification of receptor mediation of in vivo drug effects. This assay can
      be enhanced when the stimulus effects of different doses of agonist are
      evaluated. In the present study, rats were trained to discriminate small or large
      doses of nicotine from saline, and interactions of these effects with nicotinic
      receptor antagonists and partial agonists were determined. The insurmountable
      nicotine antagonist mecamylamine blocked both the discriminative stimulus and
      response rate-reducing effects of nicotine but was less effective against the
      large dose of nicotine. The alpha4beta2*-selective, competitive antagonist
      dihydro-beta-erythrodine (DHbetaE) antagonized the discriminative stimulus
      effects of both doses but was less effective against the larger training dose of
      nicotine. Schild analyses of DHbetaE suggested that different nicotinic receptor
      populations may be mediating the stimulus effects of large and small doses of
      nicotine. This suggestion was supported by observations that the discriminative
      stimulus effects of the partial agonist cytisine were more like those of the
      large dose than of the small dose of nicotine and that cytisine antagonized the
      effects of only the small nicotine dose. Varenicline produced nicotine-like
      effects in both training dose groups but reduced the discriminative stimulus
      effects of intermediate doses of nicotine in the group trained to the small dose
      of nicotine. Overall, these results suggest that small doses of nicotine produce
      their stimulus effects via alpha4beta2* nicotine receptors, whereas larger doses
      of nicotine recruit additional nicotine receptor subtypes, as revealed by drug
      discrimination assays in rats.

PMID- 21730012
TI  - Generation and characterization of a Cyp2f2-null mouse and studies on the role of
      CYP2F2 in naphthalene-induced toxicity in the lung and nasal olfactory mucosa.
AB  - The CYP2F enzymes, abundantly expressed in the respiratory tract, are active
      toward many xenobiotic compounds, including naphthalene (NA). However, the
      precise roles of these enzymes in tissue-selective chemical toxicity have been
      difficult to resolve. A Cyp2f2-null mouse was generated in this study by
      disrupting the Cyp2f2 fourth exon. Homozygous Cyp2f2-null mice, which had no
      CYP2F2 expression and showed no changes in the expression of other P450 genes
      examined, were viable and fertile and had no in utero lethality or developmental
      deficits. The loss of CYP2F2 expression led to substantial decreases in the in
      vitro catalytic efficiency of microsomal NA epoxygenases in lung (up to ~160
      fold), liver (~3-fold), and nasal olfactory mucosa (OM; up to ~16-fold), and
      significant decreases in rates of systemic NA (300 mg/kg i.p.) clearance. The
      Cyp2f2-null mice were largely resistant to NA-induced cytotoxicity, when examined
      at 24 h after NA dosing (at 300 mg/kg i.p.), and to NA-induced depletion of total
      nonprotein sulfhydryl (NPSH), examined at 2 h after dosing, in the lungs. In
      contrast, the loss of CYP2F2 expression did not alleviate NA-induced NPSH
      depletion or tissue toxicity in the OM. Mouse CYP2F2 clearly plays an essential
      role in the bioactivation and toxicity of NA in the lung but not in the OM. The
      Cyp2f2-null mouse should be valuable for studies on the role of CYP2F2 in the
      metabolism and toxicity of numerous other xenobiotic compounds and for future
      production of a CYP2F1-humanized mouse.

PMID- 21730013
TI  - A clopidogrel-insensitive inducible pool of P2Y12 receptors contributes to
      thrombus formation: inhibition by elinogrel, a direct-acting, reversible P2Y12
      antagonist.
AB  - It is known that hepatic metabolism limits the antiaggregatory activity of
      clopidogrel and, as a consequence, its clinical benefits. In this study, we
      investigated whether other factors exist that could account for clopidogrel's
      suboptimal antithrombotic activity. Using an in vivo murine FeCl(3) thrombosis
      model coupled with intravital microscopy, we found that at equivalent, maximal
      levels of inhibition of ADP-induced platelet aggregation, clopidogrel (50 mg/kg
      p.o.) failed to reproduce the phenotype associated with P2Y(12) deficiency.
      However, elinogrel (60 mg/kg p.o.), a direct-acting reversible P2Y(12)
      antagonist, achieved maximal levels of inhibition in vivo, and its administration
      (1 mg/kg i.v.) abolished residual thrombosis associated with clopidogrel dosing.
      Because elinogrel is constantly present in the plasma, whereas the active
      metabolite of clopidogrel exists for ~2 h, we evaluated whether an intracellular
      pool of P2Y(12) exists that would be inaccessible to clopidogrel and contribute
      to its limited antithrombotic activity. Using saturation [(3)H]2-(methylthio)ADP
      ([(3)H]2MeSADP) binding studies, we first demonstrated that platelet stimulation
      with thrombin and convulxin (mouse) and thrombin receptor activating peptide
      (TRAP) (human) significantly increased surface expression of P2Y(12) relative to
      that of resting platelets. We next found that clopidogrel dose-dependently
      inhibited ADP-induced aggregation, signaling (cAMP), and surface P2Y(12) on
      resting mouse platelets, achieving complete inhibition at the highest dose (50
      mg/kg), but failed to block this inducible pool. Thus, an inducible pool of
      P2Y(12) exists on platelets that can be exposed upon platelet activation by
      strong agonists. This inducible pool is not blocked completely by clopidogrel,
      contributes to thrombosis in vivo, and can be blocked by elinogrel.

PMID- 21730014
TI  - Apoptotic role of IKK in T-ALL therapeutic response.
AB  - Despite considerable progress in the treatment of T cell acute lymphoblastic
      leukemia (T-ALL), it is still the highest risk malignancy among ALL. The outcome
      of relapsed patients remains dismal. The pro-survival role of NOTCH1 and NFkappaB
      in T-ALL is well documented; also, both factors were reported to be predictive of
      relapse. The NOTCH1 signaling pathway, commonly activated in T-ALL, was shown to
      enhance the transcriptional function of NFkappaB via several mechanisms. Thus,
      pharmacological inhibition of NOTCH1-NFkappaB signaling was suggested to be
      incorporated into existing T-ALL treatment protocols. However, conventional
      chemotherapy is based on activation of various types of stress, such as DNA
      damage, mitotic perturbations or endoplasmic reticulum overload. NFkappaB is
      frequently activated in response to stress and, depending on yet unknown
      mechanisms, it either protects cells from the drug action or mediates apoptosis.
      Here, we report that T-ALL cells respond to NFkappaB inhibition in opposite ways
      depending on whether they were treated with a stress-inducing chemotherapeutic
      agent or not. Moreover, we found that NOTCH1 enhances NFkappaB apoptotic function
      in the stressed cells. The data argue for further studies of NFkappaB status in T
      ALL patients on different treatment protocols and the impact of activating NOTCH1
      mutations on treatment response.

PMID- 21730015
TI  - Short-term effects of melatonin and pinealectomy on serotonergic neuronal
      activity across the light-dark cycle.
AB  - Melatonin (MLT) and serotonin (5-HT) are two biosynthetically related compounds
      implicated in several common physiological functions and the etiology of mood
      disorders. How they interact, though, is not yet fully understood. In this study,
      single-unit extracellular recordings were used to monitor dorsal raphe nucleus
      (DR) 5-HT neuronal activity in anesthetized rats, under basal conditions (CTRL),
      in response to MLT administration, and after pinealectomy (PX) across the light
      dark cycle. Under basal conditions, the number of spontaneously active 5-HT
      neurons and their firing rate were both significantly lower in the dark phase. In
      the light phase, administration of MLT at low doses (0.5-1 mg/kg, i.v.) decreased
      5-HT firing activity. This inhibitory effect of MLT was completely blocked by the
      MT1/MT2 receptor antagonist luzindole, but not by the selective MT(2) receptor
      antagonist 4P-PDOT, the selective 5-HT(1A) receptor antagonist WAY100635, or by
      the alpha2 adrenoceptor antagonist idazoxan. In the opposite experiment, PX
      increased 5-HT firing activity in the dark phase, and this was reversed by MLT
      administration (1 mg/kg, i.v.). Finally, in a forced swim test, MLT (1 mg/kg,
      i.p.) increased immobility time and decreased swimming behavior. Together, these
      results suggest that nocturnal MLT secretion imposes tonic inhibitory control
      over a sub-population of DR 5-HT neurons. This MLT-induced decrease in 5-HT
      neurotransmission may represent a biological mechanism underlying mood disorders
      characterized by increased MLT secretion, such as seasonal affective disorder.

PMID- 21730016
TI  - Chronic tiagabine administration and aggressive responding in individuals with a
      history of substance abuse and antisocial behavior.
AB  - Anticonvulsants, notably those which modulate GABA activity, have shown efficacy
      in reducing aggressive behavior. Previously, we found dose-related decreases in
      human aggressive responding following acute tiagabine administration. Here, we
      examined the effects of chronic tiagabine over a 5-week period. Twelve
      individuals at increased risk for aggressive and violent behavior (currently on
      parole/probation with personality and/or substance use disorders) were randomly
      assigned to placebo (n = 6) or an escalating dose sequence of placebo, 4 mg, 8
      mg, 12 mg, placebo (n = 6). Data were analyzed using both frequentist and
      Bayesian mixed models, evaluating aggressive behavior as a function of time, dose
      condition, and their interaction. For aggressive responding, there was a
      significant interaction of drug condition and time. Aggression in the tiagabine
      condition decreased for each additional week in the study, while participants in
      the placebo condition failed to demonstrate similar change over time. For
      monetary-reinforced responding, no drug or drug by time interactions were
      observed, suggesting specificity of drug effects on aggression. The small number
      of subjects limits the generality of the findings, and previous studies with
      tiagabine are limited to acute dosing and case report investigations. However,
      the present data provide an indication that tiagabine merits further examination
      as an agent for management of impulsive aggression.

PMID- 21730017
TI  - Phase I studies on the safety, tolerability, pharmacokinetics and
      pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist.
AB  - The orexin system plays a major role in the integration of metabolic and
      circadian influences that drive wakefulness. This paper describes initial Phase I
      trials of a novel dual orexin receptor antagonist SB-649868 that has demonstrated
      preclinical potential for treatment of sleep disorders. The trial designs
      included a single ascending dose escalation study (dose range: 10-80 mg in the
      fed and fasted states) and a multiple repeat dose study (dose range: 5-30 mg in
      the fed state) enrolling a total of 103 male volunteer subjects. SB-649868 was
      well tolerated at all doses in this study population, with mechanism-related
      adverse events (e.g. somnolence and fatigue) observed in a majority of subjects
      after 60 and 80 mg single doses. Although total drug exposure was similar in the
      fed and fasted states, the rate, but not the extent, of absorption increased in
      the fed state, resulting in an increased C(max). The typical estimated half-life
      of SB-649868 was 3-6 h - comparable with currently used hypnotic agents. Repeated
      administration of SB-649868 dose-dependently increased exposure to simvastatin
      (10 mg), suggesting CYP3A4 inhibition ranging from very mild (5 mg) to strong (30
      mg). Evening dosing resulted in significant dose-dependent improvement in latency
      to persistent sleep, total sleep time and wake after sleep onset as measured by
      polysomnography. Next-morning testing did not detect evidence of residual
      cognitive effects. Results of these trials support further investigation of SB
      649868 and other dual orexin receptor antagonists as potentially effective and
      well-tolerated treatments for patients with sleep disorders.

PMID- 21730018
TI  - The course of brain abnormalities in schizophrenia: can we slow the progression?
AB  - There is convincing evidence that schizophrenia is characterized by progressive
      brain volume changes during the course of the illness. In a large longitudinal
      study it was shown that different age-related trajectories of brain tissue loss
      are present in patients compared with healthy subjects, suggesting that brain
      maturation that occurs in the third and fourth decade of life is abnormal in
      schizophrenia. Studies show that medication intake is an important confounding
      factor when interpreting brain volume (change) abnormalities. Atypical
      antipsychotics have been found to be related to smaller decreases in tissue loss.
      Moreover, independent of antipsychotic medication intake, the brain volume
      abnormalities appear associated to the outcome of the illness. Before being able
      to intervene with therapies and prevent the brain from shrinking, one has to
      understand the underlying mechanism of the progressive changes in the brains of
      schizophrenia patients.

PMID- 21730019
TI  - Phospholipase Czeta binding to PtdIns(4,5)P2 requires the XY-linker region.
AB  - Phospholipase C-zeta (PLCzeta) is a strong candidate for the mammalian sperm
      derived factor that triggers the Ca(2+) oscillations required for egg activation
      at fertilization. PLCzeta lacks a PH domain, which targets PLCdelta1 to the
      phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) substrate in the plasma
      membrane. Previous studies failed to detect PLCzeta in the plasma membrane, hence
      the means of PLCzeta binding to PtdIns(4,5)P(2) is unclear. We find that the
      PLCzeta XY linker, but not the C2 domain, exhibits robust binding to
      PtdIns(4,5)P(2) or to liposomes containing near-physiological levels of
      PtdIns(4,5)P(2). The role of positively charged residues within the XY linker was
      addressed by sequentially substituting alanines for three lysine residues, K374,
      K375 and K377. Microinjection of these mutants into mouse eggs enabled their
      Ca(2+) oscillation-inducing activities to be compared with wild-type PLCzeta. The
      XY-linker mutant proteins were purified and the in vitro PtdIns(4,5)P(2)
      hydrolysis and binding properties were monitored. Successive reduction of net
      positive charge within the PLCzeta XY linker significantly affects both in vivo
      Ca(2+)-oscillation-inducing activity and in vitro PtdIns(4,5)P(2) interaction of
      mouse PLCzeta. Our data suggest that positively charged residues within the XY
      linker play an important role in the PLCzeta interaction with PtdIns(4,5)P(2), a
      crucial step in generating the Ca(2+) activation signal that is essential for
      fertilization in mammals.

PMID- 21730020
TI  - Notch gain of function in mouse periocular mesenchyme downregulates FoxL2 and
      impairs eyelid levator muscle formation, leading to congenital blepharophimosis.
AB  - Notch signaling is pivotal for the morphogenesis and homeostasis of many tissues.
      We found that aberrant Notch activation in mouse neural-crest-derived periocular
      mesenchymal cells (POMCs), which contribute to the formation of corneal and
      eyelid stroma, results in blepharophimosis. Compound transgenic mice
      overexpressing the Notch1 intracellular domain (N1-ICD) in POMCs (POMC(N1-ICD))
      showed relatively minor effects on the cornea, but increased cell apoptosis and
      decreased cell proliferation during eyelid morphogenesis. Eyelid closure at E15.5
      and eyelid formation at birth were incomplete. In further analyses,
      overexpression of N1-ICD impaired eyelid levator smooth muscle formation by
      downregulating the transcription factor FoxL2. This is similar to the effect of
      haploinsufficiency of FOXL2 in humans, which results in type II BPES
      (blepharophimosis, ptosis and epicanthus inversus syndrome). In vitro studies
      showed that FoxL2 expression is augmented by a low dose of N1-ICD but was
      downregulated by a high dose, depending on the extent of Hes-1 and Hey-1
      activation. Moreover, transfection of CMV-FoxL2 enhanced alpha-SMA promoter
      activity. These data strongly imply that a physiologically low level of Notch1 is
      crucial for proper FoxL2 expression in POMCs, which is, in turn, essential for
      Mueller muscle formation and normal eyelid development.

PMID- 21730021
TI  - A novel role for neural cell adhesion molecule in modulating insulin signaling
      and adipocyte differentiation of mouse mesenchymal stem cells.
AB  - Neural cell adhesion molecule (NCAM) has recently been found on adult stem cells,
      but its biological significance remains largely unknown. In this study, we used
      bone-marrow-derived mesenchymal stem cells (MSCs) from wild-type and NCAM
      knockout mice to investigate the role of NCAM in adipocyte differentiation. It
      was demonstrated that NCAM isoforms 180 and 140 but not NCAM-120 are expressed on
      almost all wild-type MSCs. Upon adipogenic induction, Ncam(-/-) MSCs exhibited a
      marked decrease in adipocyte differentiation compared with wild-type cells. The
      role of NCAM in adipocyte differentiation was also confirmed in NCAM-silenced
      preadipocyte 3T3-L1 cells, which also had a phenotype with reduced adipogenic
      potential. In addition, we found that Ncam(-/-) MSCs appeared to be insulin
      resistant, as shown by their impaired insulin signaling cascade, such as the
      activation of the insulin-IGF-1 receptor, PI3K-Akt and CREB pathways. The PI3K
      Akt inhibitor, LY294002, completely blocked adipocyte differentiation of MSCs,
      unveiling that the reduced adipogenic potential of Ncam(-/-) MSCs is due to
      insulin resistance as a result of loss of NCAM function. Furthermore, insulin
      resistance of Ncam(-/-) MSCs was shown to be associated with induction of tumor
      necrosis factor alpha (TNF-alpha), a key mediator of insulin resistance. Finally,
      we demonstrated that re-expression of NCAM-180, but not NCAM-140, inhibits
      induction of TNF-alpha and thereby improves insulin resistance and adipogenic
      potential of Ncam(-/-) MSCs. Our results suggest a novel role of NCAM in
      promoting insulin signaling and adipocyte differentiation of adult stem cells.
      These findings raise the possibility of using NCAM intervention to improve
      insulin resistance.

PMID- 21730022
TI  - Immunoregulatory molecule B7-H1 (CD274) contributes to skin carcinogenesis.
AB  - B7-H1 (CD274), a member of the B7 family of coinhibitory molecules, is often
      induced in human tumors and its expression is closely correlated with a poor
      prognosis or higher malignancy grade. Tumor-associated B7-H1 is implicated in
      mechanisms of immune escape. Under inflammatory conditions, B7-H1 is also
      inducible in normal epithelial cells, but little is known about its involvement
      in the conversion of normal cells to tumor cells. We recently found that skin
      specific expression of B7-H1 accelerates chemically induced carcinogenesis of
      squamous cell carcinoma (SCC), despite impaired skin inflammatory responses, in
      B7-H1 transgenic (B7-H1tg) mice. B7-H1tg-derived keratinocytes (KC) and SCCs
      exhibited a marked reduction of E-cadherin, and B7-H1tg-originated SCCs showed
      elevated expression of the transcription factors Slug and Twist, suggesting that
      B7-H1 overexpression in KCs promotes the epithelial-mesenchymal transition and
      accelerates carcinogenesis. This review discusses the diverse functions of B7-H1
      in carcinogenesis and cancer progression, and considers future directions for
      developing cancer therapy targeting B7-H1.

PMID- 21730023
TI  - TLR4 engagement during TLR3-induced proinflammatory signaling in dendritic cells
      promotes IL-10-mediated suppression of antitumor immunity.
AB  - Toll-like receptor (TLR) agonists are promising adjuvants for immune therapy of
      cancer, but their potential efficacy as single or combinatorial agents has yet to
      be fully evaluated. Here, we report that among all TLR agonists tested, dendritic
      cells (DC) stimulated with the TLR3 agonist polyI:C displayed the strongest
      activity in stimulating proinflammatory responses and the production of melanoma
      antigen-specific CD8(+) T cells. Simultaneous treatment with TLR7/8 agonists
      further improved these responses, but the inclusion of bacterial
      lipopolysaccharide (LPS), a TLR4 agonist, suppressed proinflammatory cytokine
      production. This inhibition was contingent upon rapid induction of the
      suppressive cytokine interleukin (IL)-10 by LPS, leading to dysregulated immune
      responses and it could be reversed by signal transducers and activators of
      transcription 3 knockdown, p38 blockade or antibodies to IL-10 and its receptor.
      Our findings show how certain TLR agonist combinations can enhance or limit DC
      responses associated with antitumor immunity, through their relative ability to
      induce IL-10 pathways that are immune suppressive.

PMID- 21730024
TI  - YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in
      differentiation and cell growth.
AB  - The Y-box binding protein 1 (YB-1) is upregulated in many human malignancies
      including glioblastoma (GBM). It is also essential for normal brain development,
      suggesting that YB-1 is part of a neural stem cell (NSC) network. Here, we show
      that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal
      brain tissues but not in terminally differentiated primary astrocytes.
      Conversely, YB-1 knockout mice had reduced Sox-2, nestin, and musashi-1
      expression in the SVZ. Although primary murine neurospheres were rich in YB-1,
      its expression was lost during glial differentiation. Glial tumors often express
      NSC markers and tend to loose the cellular control that governs differentiation;
      therefore, we addressed whether YB-1 served a similar role in cancer cells. YB-1,
      Sox-2, musashi-1, Bmi-1, and nestin are coordinately expressed in SF188 cells and
      9/9 GBM patient-derived primary brain tumor-initiating cells (BTIC). Silencing YB
      1 with siRNA attenuated the expression of these NSC markers, reduced neurosphere
      growth, and triggered differentiation via coordinate loss of GSK3-beta.
      Furthermore, differentiation of BTIC with 1% serum or bone morphogenetic protein
      4 suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during
      differentiation of normal human NSCs. Consistent with these observations, YB-1
      expression increased with tumor grade (n = 49 cases). YB-1 was also coexpressed
      with Bmi-1 (Spearmans 0.80, P > 0.001) and Sox-2 (Spearmans 0.66, P > 0.001)
      based on the analysis of 282 cases of high-grade gliomas. These proteins were
      highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In
      conclusion, YB-1 correlatively expresses with NSC markers where it functions to
      promote cell growth and inhibit differentiation.

PMID- 21730025
TI  - Echocardiographic evaluation before bidirectional Glenn operation in functional
      single-ventricle heart disease: comparison to catheter angiography.
AB  - BACKGROUND: Cardiac catheterization is routinely performed in patients with
      single ventricle before bidirectional Glenn operation (BDG). There is interest in
      noninvasive evaluation alone before BDG, but concern for echocardiography
      successfully imaging the relevant anatomy persists. We evaluated the accuracy of
      echocardiographic imaging of vascular anatomy. METHODS AND RESULTS: Diagnostic
      images of 130 patients who had echocardiography and catheterization before BDG
      were reviewed; diameters of the pulmonary arteries (PAs) and aortic arch were
      measured, and stenoses were recorded. Patient and procedural factors associated
      with echocardiographic imaging were analyzed. Median age at echocardiography was
      4 months; the most common diagnosis was hypoplastic left heart syndrome (55%).
      The left PA was imaged by echocardiography in 83 patients (64%), with 4 of 21
      stenoses (19%) diagnosed by catheterization identified; similarly, the right PA
      was imaged in 81 (62%), and 3 of 17 stenoses (18%) were identified. The distal
      aortic arch was visualized in 104 (80%), with successful identification of 21 of
      27 (78%) of coarctations diagnosed by catheterization. Complete vascular
      echocardiography (visualization of PAs and aortic arch) occurred in 43% and was
      not obtained more frequently with sedation. CONCLUSIONS: In a large cohort of
      patients presenting for BDG, evaluation by echocardiography frequently failed to
      image the PAs and missed the majority of PA stenoses. Sedation did not appear to
      improve the performance of echocardiography for evaluation of the PAs.
      Echocardiography cannot be relied on as the sole investigation before BDG.

PMID- 21730026
TI  - Diagnostic value of vena contracta area in the quantification of mitral
      regurgitation severity by color Doppler 3D echocardiography.
AB  - BACKGROUND: Accurate quantification of mitral regurgitation (MR) is important for
      patient treatment and prognosis. Three-dimensional echocardiography allows for
      the direct measure of the regurgitant orifice area (ROA) by 3D-guided planimetry
      of the vena contracta area (VCA). We aimed to (1) establish 3D VCA ranges and
      cutoff values for MR grading, using the American Society of Echocardiography
      recommended 2D integrative method as a reference, and (2) compare 2D and 3D
      methods of ROA to establish a common calibration for MR grading. METHODS AND
      RESULTS: Eighty-three patients with at least mild MR underwent 2D and 3D
      echocardiography. Direct planimetry of VCA was performed by 3D echocardiography.
      Two-dimensional quantification of MR included 2D ROA by proximal isovelocity
      surface area (PISA) method, vena contracta width, and ratio of jet area to left
      atrial area. There were significant differences in 3D VCA among patients with
      different MR grades. As assessed by receiver operating characteristic analysis,
      3D VCA at a best cutoff value of 0.41 cm(2) yielded 97% of sensitivity and 82% of
      specificity to differentiate moderate from severe MR. There was significant
      difference between 2D ROA and 3D VCA in patients with functional MR, resulting in
      an underestimation of ROA by 2D PISA method by 27% as compared with 3D VCA.
      Multivariable regression analysis showed functional MR as etiology was the only
      predictor of underestimation of ROA by the 2D PISA method. CONCLUSIONS: Three
      dimensional VCA provides a single, directly visualized, and reliable measurement
      of ROA, which classifies MR severity comparable to current clinical practice
      using the American Society of Echocardiography-recommended 2D integrative method.
      The 3D VCA method improves accuracy of MR grading compared with the 2D PISA
      method by eliminating geometric and flow assumptions, allowing for uniform
      clinical grading cutoffs and ranges that apply regardless of etiology and orifice
      shape.

PMID- 21730027
TI  - Incremental prognostic value of cardiac computed tomography in coronary artery
      disease using CONFIRM: COroNary computed tomography angiography evaluation for
      clinical outcomes: an InteRnational Multicenter registry.
AB  - BACKGROUND: Large multicenter studies validating the prognostic value of coronary
      computed tomographic angiography (CCTA) and left ventricular ejection fraction
      (LVEF) are lacking. We sought to confirm the independent and incremental
      prognostic value of coronary artery disease (CAD) severity measured using 64
      slice CCTA over LVEF and clinical variables. METHODS AND RESULTS: A large
      international multicenter registry (CONFIRM Registry) was queried, and CCTA
      patients with LVEF data on CCTA were screened. Patients with a history of
      myocardial infarction, coronary revascularization, or cardiac transplantation
      were excluded. The National Cholesterol Education Program-Adult Treatment Panel
      III risk was calculated for each patient, and CCTA was evaluated for CAD severity
      (normal, nonobstructive, non-high-risk, or high-risk CAD) and LVEF <50%. Patients
      were followed for an end point of all-cause mortality; 27 125 patients underwent
      CCTA at 12 participating centers, with a total of 14 064 patients meeting the
      analysis criteria. Follow-up was available for 13 966 (99.3%) patients (mean
      follow-up of 22.5 months; 95% confidence interval, 22.3 to 22.7 months). All
      cause mortality (271 deaths) occurred in 0.65% of patients without coronary
      atherosclerosis, 1.99% of patients with nonobstructive CAD, 2.90% of patients
      with non-high-risk CAD, and 4.95% for patients with high-risk CAD. Multivariable
      analysis confirmed that LVEF <50% (hazard ratio, 2.74; 95% confidence interval,
      2.12 to 3.51) and CAD severity (hazard ratio,1.58; 95% confidence interval, 1.42
      to 1.76) were predictors of all-cause mortality, and CAD severity had incremental
      value over LVEF and clinical variables. CONCLUSIONS: Our results demonstrate that
      CCTA measures of CAD severity and LVEF have independent prognostic value.
      Incorporation of CAD severity provides incremental value for predicting all-cause
      death over routine clinical predictors and LVEF in patients with suspected
      obstructive CAD.

PMID- 21730028
TI  - Four out of eight genes in a mouse chromosome 7 congenic donor region are
      candidate obesity genes.
AB  - We previously identified a region of mouse chromosome 7 that influences body fat
      mass in F2 littermates of congenic * background intercrosses. Current analyses
      revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318)
      promoted a twofold increase in adiposity in homozygous lines of 318 compared with
      background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted
      through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor
      region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and
      contains a maximum of eight protein coding genes. Quantitative PCR in whole
      brain, liver, and gonadal white adipose tissue (GWAT) revealed differential
      expression between genotypes for three genes in females and two genes in males.
      Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain
      for females and males and in GWAT for females only. Both sexes of 318 mice had
      reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family
      with sequence similarity 174 member b (Fam174b) had increased expression in 318
      females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced
      expression in 318 males. No donor region genes were differentially expressed in
      liver. Sequence analysis of coding exons for all genes in the 318 donor region
      revealed only one single nucleotide polymorphism that produced a nonsynonymous
      missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of
      using expression and sequence to identify quantitative trait genes underlying
      obesity even in small genomic regions.

PMID- 21730029
TI  - Transcriptome and translational signaling following endurance exercise in trained
      skeletal muscle: impact of dietary protein.
AB  - Postexercise protein feeding regulates the skeletal muscle adaptive response to
      endurance exercise, but the transcriptome guiding these adaptations in well
      trained human skeletal muscle is uncharacterized. In a crossover design, eight
      cyclists ingested beverages containing protein, carbohydrate and fat (PTN: 0.4,
      1.2, 0.2 g/kg, respectively) or isocaloric carbohydrate and fat (CON: 1.6, 0.2
      g/kg) at 0 and 1 h following 100 min of cycling. Biopsies of the vastus lateralis
      were collected at 3 and 48 h following to determine the early and late
      transcriptome and regulatory signaling responses via microarray and immunoblot.
      The top gene ontology enriched by PTN were: muscle contraction, extracellular
      matrix--signaling and structure, and nucleoside, nucleotide, and nucleic acid
      metabolism (3 and 48 h); developmental processes, immunity, and defense (3 h);
      glycolysis, lipid and fatty acid metabolism (48 h). The transcriptome was also
      enriched within axonal guidance, actin cytoskeletal, Ca2+, cAMP, MAPK, and PPAR
      canonical pathways linking protein nutrition to exercise-stimulated signaling
      regulating extracellular matrix, slow-myofibril, and metabolic gene expression.
      At 3 h, PTN attenuated AMPKalpha1Thr172 phosphorylation but increased
      mTORC1Ser2448, rps6Ser240/244, and 4E-BP1-gamma phosphorylation, suggesting
      increased translation initiation, while at 48 h AMPKalpha1Thr172 phosphorylation
      and PPARG and PPARGC1A expression increased, supporting the late metabolic
      transcriptome, relative to CON. To conclude, protein feeding following endurance
      exercise affects signaling associated with cell energy status and translation
      initiation and the transcriptome involved in skeletal muscle development, slow
      myofibril remodeling, immunity and defense, and energy metabolism. Further
      research should determine the time course and posttranscriptional regulation of
      this transcriptome and the phenotype responding to chronic postexercise protein
      feeding.

PMID- 21730030
TI  - Kinetic characterization of rat hepatic uptake of 16 actively transported drugs.
AB  - To explore the determinants of hepatic uptake, 16 compounds were investigated
      with different physicochemical and disposition characteristics, including five
      statins, three sartans, saquinavir, ritonavir, erythromycin, clarithromycin,
      nateglinide, repaglinide, fexofenadine, and bosentan. Freshly isolated rat
      hepatocytes in suspension were used with the oil-spin method to generate kinetic
      parameters. Clearances, via passive diffusion (P(diff)) and active uptake
      (CL(active), characterized by maximal uptake rate and K(m)), were estimated from
      the initial uptake rate data over a 0.01 to 100 MUM concentration range. The K(m)
      values had a range of 15-fold, with 10 of the 16 drugs with K(m) < 10 MUM (median
      6 MUM). Both CL(active) and P(diff) ranged over 100-fold (median 188 and 14
      MUl/min/106 cells). Assessment of the relative contribution of P(diff) and
      CL(active) indicated that, at low concentrations (approximately 0.1 MUM), the
      active process contributes >80% to the overall uptake for 13 drugs. Although high
      P(diff) values were obtained for ritonavir and repaglinide, active process
      contributed predominantly to uptake; in contrast, high passive permeability
      dominates over transporter-mediated uptake for saquinavir over the full
      concentration range. For bosentan and erythromycin, active and passive processes
      were equally important. Hepatocyte-to-medium unbound concentration ratio was >10
      for 9 of the 16 drugs, ranging from 2 to 494 for bosentan and atorvastatin,
      respectively. Some drugs showed extensive intracellular binding (fraction unbound
      range 0.01-0.6), which was not correlated with active uptake. LogD7.4 correlated
      significantly with P(diff) and the extent of intracellular binding but not with
      active uptake. This study provides systematic assessment of the role of active
      uptake relative to the passive process; implications of the findings are
      discussed.

PMID- 21730031
TI  - Effects of intrarectally administered omeprazole paste on gastric fluid pH in
      healthy adult horses.

PMID- 21730032
TI  - Dystrophin-deficient muscular dystrophy in an Alaskan malamute.

PMID- 21730033
TI  - Evaluation of risks of foot-and-mouth disease in Scotland to assist with decision
      making during the 2007 outbreak in the UK.
AB  - An outbreak of foot-and-mouth disease (FMD) occurred in Surrey on August 3, 2007.
      A Great Britain-wide ban on livestock movements was implemented immediately. This
      coincided with the start of seasonal sheep movements off the hills in Scotland;
      the majority of these animals are sold via markets. The ban therefore posed
      severe economic and animal-welfare hardships if it was to last through September
      and beyond. The Scottish Government commissioned an analysis to assess the risk
      of re-opening markets given the uncertainty about whether FMD had entered
      Scotland. Tracing of livestock moved from within the risk zone in England between
      July 16 and August 3 identified contact chains to 12 Scottish premises;
      veterinary field inspections found a further three unrecorded movements. No signs
      of infection were found on these holdings. Under the conservative assumption that
      a single unknown Scottish holding was infected with FMD, an estimate of the time
      dependent probability of Scotland being FMD free given no detection was made.
      Analyses indicated that if FMD was not detected by early to mid-September then it
      was highly probable that Scotland was FMD free. Risk maps were produced to
      visualise the potential spread of FMD across Scotland if it was to spread either
      locally or via market sales.

PMID- 21730034
TI  - Suspected bog asphodel (Narthecium ossifragum) toxicity in cattle in North Wales.

PMID- 21730035
TI  - Comparison of oestrus detection methods in dairy cattle.
AB  - Sixty-seven Holstein-Friesian cows, from 20 days postpartum, were recruited into
      the study and fitted with both a pedometer (SAE Afikim) and a Heatime neck collar
      (SCR Engineers) and allocated a heat mount detector (either scratchcard
      [Dairymac] or KaMaR [KaMaR]) or left with none, relying only on farm staff
      observation. Common production stressors and other factors were assessed to
      determine their impact on the ability of each method to accurately detect oestrus
      and to investigate effects on the frequency of false-positive detections. Only 74
      per cent of all potential oestrus periods (episodes of low progesterone) were
      identified by combining information from all methods. There was no difference
      between the methods in terms of sensitivity for detecting 'true oestrus events'
      (approximately 60 per cent), with the exception of scratchcards, which were less
      efficient (36 per cent). Pedometers and KaMaRs had higher numbers of false
      positive identifications. No production stressors had any consequence on false
      positives. The positive predictive values for neck collars or observation by farm
      staff were higher than those of other methods, and combining these two methods
      yielded the best results. Neck collars did not detect any of the nine oestrus
      events occurring in three cows with a body condition score (BCS) of less than 2,
      and the efficiency of correctly identifying oestrus was also reduced by high milk
      yield (odds ratio [OR]=0.34). Pedometer efficiency was reduced by lameness, low
      BCS or high milk yield (OR=0.42, 0.15 or 0.30, respectively).

PMID- 21730036
TI  - Localised tetanus in a cat.

PMID- 21730037
TI  - Mechanical assessment of elastin integrity in fibrillin-1-deficient carotid
      arteries: implications for Marfan syndrome.
AB  - AIMS: Elastin is the primary component of elastic fibres in arteries, which
      contribute significantly to the structural integrity of the wall. Fibrillin-1 is
      a microfibrillar glycoprotein that appears to stabilize elastic fibres
      mechanically and thereby to delay a fatigue-induced loss of function due to long
      term repetitive loading. Whereas prior studies have addressed some aspects of
      ageing-related changes in the overall mechanical properties of arteries in mouse
      models of Marfan syndrome, we sought to assess for the first time the load
      carrying capability of the elastic fibres early in maturity, prior to the
      development of ageing-related effects, dilatation, or dissection. METHODS AND
      RESULTS: We used elastase to degrade elastin in common carotid arteries excised,
      at 7-9 weeks of age, from a mouse model (mgR/mgR) of Marfan syndrome that
      expresses fibrillin-1 at 15-25% of normal levels. In vitro biaxial mechanical
      tests performed before and after exposure to elastase suggested that the elastic
      fibres exhibited a nearly normal load-bearing capability. Observations from
      nonlinear optical microscopy suggested further that competent elastic fibres not
      only contribute to load-bearing, they also increase the undulation of collagen
      fibres, which endows the normal arterial wall with a more compliant response to
      pressurization. CONCLUSION: These findings support the hypothesis that it is an
      accelerated fatigue-induced damage to or protease-related degradation of
      initially competent elastic fibres that render arteries in Marfan syndrome
      increasingly susceptible to dilatation, dissection, and rupture.

PMID- 21730038
TI  - Inflammatory response in rat lungs with recurrent exposure to welding fumes: a
      transcriptomic approach.
AB  - As chronic exposure to welding fumes causes pulmonary diseases, such as
      pneumoconiosis, public concern has increased regarding continued exposure to
      these hazardous gases in the workplace. In a previous study, the inflammatory
      response to welding fume exposure was analysed in rat lungs in the case of
      recurrent exposure and recovery periods. Thus using lung samples, well-annotated
      by histological observation and biochemical analysis, this study examines the
      gene expression profiles to identify phenotype-anchored genes corresponding to
      lung inflammation and the repair phenomenon after recurrent welding fume
      exposure. Seven genes (Mmp12, Cd5l, LOC50101, LOC69183, Spp1, and Slc26a4) were
      found to be significantly up-regulated according to the severity of the lung
      injury. In addition, the transcription and translation of Trem2, which was up
      regulated in response to the repair process, were validated using a real-time
      polymerase chain reaction, Western blotting, and immunohistochemistry. The
      differentially expressed genes in the exposure and recovery groups were also
      classified using k-means and hierarchical clustering, plus their toxicological
      function and canonical pathways were further analysed using Ingenuity Pathways
      Analysis Software. As a result, this comprehensive and integrative analysis of
      the transcriptional changes that occur during repeated exposure provides
      important information on the inflammation and repair processes after welding-fume
      induced lung injury.

PMID- 21730039
TI  - Corn baked by burning coal triggered overexpression of osteopontin in hepatocytes
      of rats following fluorosis.
AB  - OBJECTIVE: To observe the expression of osteopontin (OPN) in hepatocytes of rats
      fed with corn baked by burning coal from fluorosis areas and a deficiency of
      calcium/protein intake following fluorosis. METHODS: A total of 48 Wistar rats as
      objects were randomly assorted into four groups: dose-free fluorine group, which
      were mainly fed with fluorine-free corn (56% structurally), dose-free fluorine
      with biased dietary group, which were fed with lower contents of protein (119.41
      g/kg) and calcium (0.68 g/kg), high-dose fluorine group (fluorine contents: 104.2
      mg/kg), and high-dose fluorine with biased dietary group. After 180 days of
      cultivation, the contents of fluorine in the bones of rats were tested for the
      assessment of construction of fluorosis animal model. And the expression of OPN
      in hepatocytes of rats in different groups was detected with immunohistochemistry
      and reverse transcription polymerase chain reaction. RESULTS: The present study
      validated the result that OPN was overexpressed in hepatocytes following
      fluorosis after oral intake of burning coal-baked corn. OPN was expressed most
      significantly in high fluorine with biased dietary group, and the high-fluorine
      group ranked the second most; and dose-free fluorine with biased dietary group
      ranked the third. The dose-free fluorine group expressed the least OPN.
      CONCLUSION: Overexpression of OPN in hepatocytes following fluorosis after excess
      fluorine intake was involved in liver damage process, which was enhanced by
      deficiency of calcium and protein intake. The results also demonstrated that the
      development of fluorosis in Guizhou province was correlated with local baking
      staple corn as a way of excess intake of fluorine and deficiency of
      calcium/protein intake.

PMID- 21730040
TI  - Blood chromium levels of children working in gem-polishing industries in India.
AB  - The gem-polishing industry in Jaipur, India employs a substantial proportion of
      children. The process of polishing may result in exposure to chromium in working
      children. Thus, this study aims to find out the levels of chromium in these
      working children and the associated factors. Blood samples were analysed for
      chromium using atomic absorption spectrophotometer. The mean blood chromium
      levels were 2.51 +/- 1.11 mg/100 ml and 2.33 +/- 1.10 mg/100 ml in working and
      school children, respectively, which is well within the permissible levels.
      However, the practice of employing children should be totally curbed.

PMID- 21730041
TI  - EPR policies for electronics in developing Asia: an adapted phase-in approach.
AB  - The amount of e-waste is growing rapidly in developing countries, and the health
      and environmental problems resulting from poor management of this waste have
      become a concern for policy makers. In response to these challenges, a number of
      Asian developing countries have been inspired by policy developments in OECD
      countries, and have drafted legislations based on the principle of extended
      producer responsibility (EPR). However, the experiences from developed countries
      show that a successful implementation of EPR policies requires adequate
      institutions and sufficient administrative capacity. Even advanced countries are
      thus facing difficulties. This paper concludes from existing literature and from
      the authors' own observations that there seems to be a mismatch between the
      typical policy responses to e-waste problems in developing Asia and the capacity
      for successful implementation of such policies. It also notes that the e-waste
      situation in developing Asian countries is further complicated by a number of
      additional factors, such as difficulties in identifying producers, import of used
      electronic products and e-waste (sometimes illegal), and the existence of a
      strong informal waste sector. Given these challenges, the authors conclude that
      comprehensive EPR policy schemes of the kind that have been implemented in some
      advanced countries are not likely to be effective. The paper therefore proposes
      an alternative phase-in approach whereby developing Asian countries are able to
      move gradually towards EPR systems. It argues that this approach would be more
      feasible, and discusses what could be the key building blocks of each
      implementation stage.

PMID- 21730042
TI  - Recycling policies and programmes for PET drink bottles in Mexico.
AB  - Transition and emerging economies confront a steadily increasing generation of
      municipal solid waste in the form of disposable packaging. The following article
      reports the situation of soft drink bottles made of polyethylene terephthalate
      (PET) in Mexico. Since 2002 schemes following the European Green Dot principle
      have been partly implemented to place responsibility on the producer, mainly soft
      drink bottlers. Private stakeholders are responsible for national recovery
      activities. Meanwhile Government presence to promote recovery is absent. Of post
      consumer PET 75% is exported, and the newly created bottle-to-bottle (BTB) PET
      industry is confronted with bottlenecks in their post-consumer PET supply.

PMID- 21730043
TI  - High efficient waste-to-energy in Amsterdam: getting ready for the next steps.
AB  - Waste-to-energy (WtE) plants are traditionally designed for clean and economical
      disposal of waste. Design for output on the other hand was the guideline when
      projecting the HRC (HoogRendement Centrale) block of Afval Energie Bedrijf
      Amsterdam. Since commissioning of the plant in 2007, operation has continuously
      improved. In December 2010, the block's running average subsidy efficiency for
      one year exceeded 30% for the first time. The plant can increase its efficiency
      even further by raising the steam temperature to 480 degrees C. In addition, the
      plant throughput can be increased by 10% to reduce the total cost of ownership.
      In order to take these steps, good preparation is required in areas such as
      change in heat transfer in the boiler and the resulting higher temperature
      upstream of the super heaters. A solution was found in the form of combining
      measured data with a computational fluid dynamics (CFD) model. Suction and
      acoustic pyrometers are used to obtain a clear picture of the temperature
      distribution in the first boiler pass. With the help of the CFD model, the change
      in heat transfer and vertical temperature distribution was predicted. For the
      increased load, the temperature is increased by 100 degrees C; this implies a
      higher heat transfer in the first and second boiler passes. Even though the new
      block was designed beyond state-of-the art in waste-to-energy technology, margins
      remain for pushing energy efficiency and economy even further.

PMID- 21730044
TI  - Calcium signaling in neuronal development.
AB  - The development of the nervous system involves the generation of a stunningly
      diverse array of neuronal subtypes that enable complex information processing and
      behavioral outputs. Deciphering how the nervous system acquires and interprets
      information and orchestrates behaviors will be greatly enhanced by the
      identification of distinct neuronal circuits and by an understanding of how these
      circuits are formed, changed, and/or maintained over time. Addressing these
      challenging questions depends in part on the ability to accurately identify and
      characterize the unique neuronal subtypes that comprise individual circuits.
      Distinguishing characteristics of neuronal subgroups include but are not limited
      to neurotransmitter phenotype, dendritic morphology, the identity of synaptic
      partners, and the expression of constellations of subgroup-specific proteins,
      including ion channel subtypes.

PMID- 21730045
TI  - Function of the sex chromosomes in mammalian fertility.
AB  - The sex chromosomes play a highly specialized role in germ cell development in
      mammals, being enriched in genes expressed in the testis and ovary. Sex
      chromosome abnormalities (e.g., Klinefelter [XXY] and Turner [XO] syndrome)
      constitute the largest class of chromosome abnormalities and the commonest
      genetic cause of infertility in humans. Understanding how sex-gene expression is
      regulated is therefore critical to our understanding of human reproduction. Here,
      we describe how the expression of sex-linked genes varies during germ cell
      development; in females, the inactive X chromosome is reactivated before meiosis,
      whereas in males the X and Y chromosomes are inactivated at this stage. We
      discuss the epigenetics of sex chromosome inactivation and how this process has
      influenced the gene content of the mammalian X and Y chromosomes. We also present
      working models for how perturbations in sex chromosome inactivation or
      reactivation result in subfertility in the major classes of sex chromosome
      abnormalities.

PMID- 21730046
TI  - Selection in the rapid evolution of gamete recognition proteins in marine
      invertebrates.
AB  - Animal fertilization is governed by the interaction (binding) of proteins on the
      surfaces of sperm and egg. In many examples presented herein, fertilization
      proteins evolve rapidly and show the signature of positive selection (adaptive
      evolution). This review describes the molecular evolution of fertilization
      proteins in sea urchins, abalone, and oysters, animals with external
      fertilization that broadcast their gametes into seawater. Theories regarding the
      selective forces responsible for the rapid evolution driven by positive selection
      seen in many fertilization proteins are discussed. This strong selection acting
      on divergence of interacting fertilization proteins might lead to prezygotic
      reproductive isolation and be a significant factor in the speciation process.
      Since only a fraction of all eggs are fertilized and only an infinitesimal
      fraction of male gametes succeed in fertilizing an egg, gametes are obviously a
      category of entities subjected to intense selection. It is curious that this is
      never mentioned in the literature dealing with selection, perhaps because we know
      so little about fitness differences among gametes. (Ernst Mayr, 1997).

PMID- 21730047
TI  - Molecular cloning and sequence of retinoid X receptor in the green crab Carcinus
      maenas: a possible role in female reproduction.
AB  - Retinoid X receptor (RXR) belongs to an ancient superfamily of nuclear hormone
      receptors, and plays an important role in reproduction of vertebrates. However,
      the reproductive role of RXR has not been clarified in crustaceans. In this
      investigation, we first report the cloning of two alternative splice variants of
      RXR cDNA from green crab ovarian RNA. RXR mRNA levels were quantified in
      different vitellogenic stages of the crab hepatopancreas (HP) and ovary. The
      expression of RXR mRNA relative to the arginine kinase mRNA was significantly
      increased in the HP of vitellogenic crabs in a stage-dependent manner. The
      relative levels of RXR mRNA in the ovary were significantly lower in vitellogenic
      stage III crabs than in crabs in the other three stages. These data indicate that
      the HP and ovary of the crab are capable of expressing RXR, which may regulate,
      in part, vitellogenesis in the crab. We also examined the effects of methyl
      farnesoate (MF) and RXR-dsRNA treatments on vitellogenin and RXR gene expression.
      Vitellogenin and RXR mRNA levels in HP and ovarian fragments incubated in MF were
      significantly (P<0.001) higher than in control tissue fragments prepared from the
      same animal. Treatment of crabs with RXR-dsRNA significantly (P<0.001) reduced
      mRNA levels for RXR and for vitellogenin as well as MF levels in hemolymph. These
      results indicate that, MF and RXR form a complex (MF-RXR) directly and together
      stimulate ovarian development in these green crabs. This interaction of RXR, MF,
      and ovary development axis is a novel finding and is the first report to the best
      of our knowledge.

PMID- 21730048
TI  - Hierarchical organization in the amyloid core of yeast prion protein Ure2.
AB  - Formation of amyloid fibrils is involved in a range of fatal human disorders
      including Alzheimer, Parkinson, and prion diseases. Yeast prions, despite
      differences in sequence from their mammalian counterparts, share similar features
      with mammalian prions including infectivity, prion strain phenomenon, and species
      barrier and thus are good model systems for human prion diseases. Yeast prions
      normally have long prion domains that presumably form multiple beta strands in
      the fibril, and structural knowledge about the yeast prion fibrils has been
      limited. Here we use site-directed spin labeling and electron paramagnetic
      resonance (EPR) spectroscopy to investigate the structures of amyloid fibrils of
      Ure2 prion domain. We show that 15 spin-labeled Ure2 mutants, with spin labels at
      every 5th residue from position 5 to position 75, show a single-line or nearly
      single-line feature in their EPR spectra as a result of strong spin exchange
      interactions. These results suggest that a parallel in-register beta structure
      exists at these spin-labeled positions. More interestingly, we also show that
      residues in the segment 30-65 have stronger spin exchange interactions, higher
      local stability, and lower solvent accessibility than segments 5-25 and 70-75,
      suggesting different local environment at these segments. We propose a
      hierarchical organization in the amyloid core of Ure2, with the segment 30-65
      forming an inner core and the segments 5-25 and 70-75 forming an outer core. The
      hierarchical organization in the amyloid core may be a structural origin for
      polymorphism in fibrils and prion strains.

PMID- 21730049
TI  - Gain in transcriptional activity by primate-specific coevolution of melanoma
      antigen-A11 and its interaction site in androgen receptor.
AB  - Male sex development and growth occur in response to high affinity androgen
      binding to the androgen receptor (AR). In contrast to complete amino acid
      sequence conservation in the AR DNA and ligand binding domains among mammals, a
      primate-specific difference in the AR NH(2)-terminal region that regulates the
      NH(2)- and carboxyl-terminal (N/C) interaction enables direct binding to melanoma
      antigen-A11 (MAGE-11), an AR coregulator that is also primate-specific. Human,
      mouse, and rat AR share the same NH(2)-terminal (23)FQNLF(27) sequence that
      mediates the androgen-dependent N/C interaction. However, the mouse and rat AR
      FXXLF motif is flanked by Ala(33) that evolved to Val(33) in primates. Human AR
      Val(33) was required to interact directly with MAGE-11 and for the inhibitory
      effect of the AR N/C interaction on activation function 2 that was relieved by
      MAGE-11. The functional importance of MAGE-11 was indicated by decreased human AR
      regulation of an androgen-dependent endogenous gene using lentivirus short
      hairpin RNAs and by the greater transcriptional strength of human compared with
      mouse AR. MAGE-11 increased progesterone and glucocorticoid receptor activity
      independently of binding an FXXLF motif by interacting with p300 and p160
      coactivators. We conclude that the coevolution of the AR NH(2)-terminal sequence
      and MAGE-11 expression among primates provides increased regulatory control over
      activation domain dominance. Primate-specific expression of MAGE-11 results in
      greater steroid receptor transcriptional activity through direct interactions
      with the human AR FXXLF motif region and indirectly through steroid receptor
      associated p300 and p160 coactivators.

PMID- 21730050
TI  - The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is a
      mitochondrial protein that translocates to the nucleus to protect cells against
      oxidative stress.
AB  - Confocal microscopy images revealed that the tetratricopeptide repeat motif (TPR)
      domain immunophilin FKBP51 shows colocalization with the specific mitochondrial
      marker MitoTracker. Signal specificity was tested with different antibodies and
      by FKBP51 knockdown. This unexpected subcellular localization of FKBP51 was
      confirmed by colocalization studies with other mitochondrial proteins,
      biochemical fractionation, and electron microscopy imaging. Interestingly, FKBP51
      forms complexes in mitochondria with the glucocorticoid receptor and the
      Hsp90/Hsp70-based chaperone heterocomplex. Although Hsp90 inhibitors favor FKBP51
      translocation from mitochondria to the nucleus in a reversible manner, TPR domain
      deficient mutants of FKBP51 are constitutively nuclear and fully excluded from
      mitochondria, suggesting that a functional TPR domain is required for its
      mitochondrial localization. FKBP51 overexpression protects cells against
      oxidative stress, whereas FKBP51 knockdown makes them more sensitive to injury.
      In summary, this is the first demonstration that FKBP51 is a major mitochondrial
      factor that undergoes nuclear-mitochondrial shuttling, an observation that may be
      related to antiapoptotic mechanisms triggered during the stress response.

PMID- 21730051
TI  - The IQGAP1 protein is a calmodulin-regulated barbed end capper of actin
      filaments: possible implications in its function in cell migration.
AB  - IQGAP1 is a large modular protein that displays multiple partnership and is
      thought to act as a scaffold in coupling cell signaling to the actin and
      microtubule cytoskeletons in cell migration, adhesion, and cytokinesis. However
      the molecular mechanisms underlying the activities of IQGAP1 are poorly
      understood in part because of its large size, poor solubility and lack of
      functional assays to challenge biochemical properties in various contexts. We
      have purified bacterially expressed recombinant human IQGAP1. The protein binds
      Cdc42, Rac1, and the CRIB domain of N-WASP in a calmodulin-sensitive fashion. We
      further show that in addition to bundling of filaments via a single N-terminal
      calponin-homology domain, IQGAP1 actually regulates actin assembly. It caps
      barbed ends, with a higher affinity for ADP-bound terminal subunits (K(B) = 4
      nM). The barbed end capping activity is inhibited by calmodulin, consistent with
      calmodulin binding to IQGAP1 with a K(C) of 40 nm, both in the absence and
      presence of Ca(2+) ions. The barbed end capping activity resides in the C
      terminal half of IQGAP1. It is possible that the capping activity of IQGAP1
      accounts for its stimulation of cell migration. We further find that bacterially
      expressed recombinant IQGAP1 fragments easily co-purify with nucleic acids that
      turn out to activate N-WASP protein to branch filaments with Arp2/3 complex. The
      present results open perspectives for tackling the function of IQGAP1 in more
      complex reconstituted systems.

PMID- 21730052
TI  - Toll-like receptor 4 (TLR4) is essential for Hsp70-like protein 1 (HSP70L1) to
      activate dendritic cells and induce Th1 response.
AB  - Toll-like receptors (TLRs) play important roles in initiation of innate and
      adaptive immune responses. Emerging evidence suggests that TLR agonists can serve
      as potential adjuvant for vaccination. Heat shock proteins (HSPs), functionally
      serving as TLR4 agonists, have been proposed to act as Th1 adjuvant. We have
      identified a novel Hsp70 family member, termed Hsp70-like protein 1 (Hsp70L1),
      shown that Hsp70L1 is a potent T helper cell (Th1) polarizing adjuvant that
      contributes to antitumor immune responses. However, the underlying mechanism for
      how Hsp70L1 exerts its Th1 adjuvant activity remains to be elucidated. In this
      study, we found that Hsp70L1 binds directly to TLR4 on the surface of DCs,
      activates MAPK and NF-kappaB pathways, up-regulates I-a(b), CD40, CD80, and CD86
      expression and promotes production of TNF-alpha, IL-1beta, and IL-12p70. Hsp70L1
      failed to induce such phenotypic maturation and cytokine production in TLR4
      deficient DCs, indicating a role for TLR4 in mediating Hsp70L1-induced DC
      activation. Furthermore, more efficient induction of carcinoembryonic antigen
      (CEA)-specific Th1 immune response was observed in mice immunized by wild-type
      DCs pulsed with Hsp70L1-CEA(576-669) fusion protein as compared with TLR4
      deficient DCs pulsed with same fusion protein. In addition, TLR4 antagonist
      impaired induction of CEA-specific human Th1 immune response in a co-culture
      system of peripheral blood lymphocytes (PBLs) from HLA-A2.1(+) healthy donors and
      autologous DCs pulsed with Hsp70L1-CEA(576-669) in vitro. Taken together, these
      results demonstrate that TLR4 is a key receptor mediating the interaction of
      Hsp70L1 with DCs and subsequently enhancing the induction of Th1 immune response
      by Hsp70L1/antigen fusion protein.

PMID- 21730053
TI  - Molecular and therapeutic characterization of anti-ectodysplasin A receptor
      (EDAR) agonist monoclonal antibodies.
AB  - The TNF family ligand ectodysplasin A (EDA) and its receptor EDAR are required
      for proper development of skin appendages such as hair, teeth, and eccrine sweat
      glands. Loss of function mutations in the Eda gene cause X-linked hypohidrotic
      ectodermal dysplasia (XLHED), a condition that can be ameliorated in mice and
      dogs by timely administration of recombinant EDA. In this study, several agonist
      anti-EDAR monoclonal antibodies were generated that cross-react with the
      extracellular domains of human, dog, rat, mouse, and chicken EDAR. Their half
      life in adult mice was about 11 days. They induced tail hair and sweat gland
      formation when administered to newborn EDA-deficient Tabby mice, with an EC(50)
      of 0.1 to 0.7 mg/kg. Divalency was necessary and sufficient for this therapeutic
      activity. Only some antibodies were also agonists in an in vitro surrogate
      activity assay based on the activation of the apoptotic Fas pathway. Activity in
      this assay correlated with small dissociation constants. When administered in
      utero in mice or at birth in dogs, agonist antibodies reverted several ectodermal
      dysplasia features, including tooth morphology. These antibodies are therefore
      predicted to efficiently trigger EDAR signaling in many vertebrate species and
      will be particularly suited for long term treatments.

PMID- 21730054
TI  - Involvement of protein kinase Cdelta/extracellular signal-regulated
      kinase/poly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine
      induced up-regulation of histamine H1 receptor gene expression in HeLa cells.
AB  - The histamine H(1) receptor (H1R) gene is up-regulated in patients with allergic
      rhinitis. However, the mechanism and reason underlying this up-regulation are
      still unknown. Recently, we reported that the H1R expression level is strongly
      correlated with the severity of allergic symptoms. Therefore, understanding the
      mechanism of this up-regulation will help to develop new anti-allergic drugs
      targeted for H1R gene expression. Here we studied the molecular mechanism of H1R
      up-regulation in HeLa cells that express H1R endogenously in response to
      histamine and phorbol 12-myristate 13-acetate (PMA). In HeLa cells, histamine
      stimulation caused up-regulation of H1R gene expression. Rottlerin, a PKCdelta
      selective inhibitor, inhibited up-regulation of H1R gene expression, but Go6976,
      an inhibitor of Ca(2+)-dependent PKCs, did not. Histamine or PMA stimulation
      resulted in PKCdelta phosphorylation at Tyr(311) and Thr(505). Activation of
      PKCdelta by H(2)O(2) resulted in H1R mRNA up-regulation. Overexpression of
      PKCdelta enhanced up-regulation of H1R gene expression, and knockdown of the
      PKCdelta gene suppressed this up-regulation. Histamine or PMA caused
      translocation PKCdelta from the cytosol to the Golgi. U0126, an MEK inhibitor,
      and DPQ, a poly(ADP-ribose) polymerase-1 inhibitor, suppressed PMA-induced up
      regulation of H1R gene expression. These results were confirmed by a luciferase
      assay using the H1R promoter. Phosphorylation of ERK and Raf-1 in response to PMA
      was also observed. However, real-time PCR analysis showed no inhibition of H1R
      mRNA up-regulation by a Raf-1 inhibitor. These results suggest the involvement of
      the PKCdelta/ERK/poly(ADP-ribose) polymerase-1 signaling pathway in histamine- or
      PMA-induced up-regulation of H1R gene expression in HeLa cells.

PMID- 21730055
TI  - Morphine withdrawal stress modulates lipopolysaccharide-induced interleukin 12
      p40 (IL-12p40) expression by activating extracellular signal-regulated kinase
      1/2, which is further potentiated by glucocorticoids.
AB  - Withdrawal stress is a common occurrence in opioid users, yet very few studies
      have examined the effects of morphine withdrawal (MW) on immune functioning or
      the role of glucocorticoids in MW-induced immunomodulation. This study
      investigated for the first time the role of glucocorticoids in MW modulation of
      LPS-induced IL-12p40, a key cytokine playing a pivotal role in immunoprotection.
      Using WT and MU-opioid receptor knock-out mice, we show that MW in vivo
      significantly attenuated LPS-induced IL-12p40 mRNA and protein expression. The
      role of glucocorticoids in MW modulation of IL-12p40 was investigated using a
      murine macrophage cell line, CRL2019, in an in vitro MW model. Interestingly, MW
      alone in the absence of glucocorticoids resulted in a significant reduction in IL
      12p40 promoter activity and mRNA and protein expression. EMSA revealed a
      concurrent decrease in consensus binding to transcription factors NFkappaB,
      Activator Protein-1, and CCAAT/enhancer-binding protein and Western blot analysis
      demonstrated a significant activation of LPS-induced ERK1/2 phosphorylation.
      Interestingly, although glucocorticoid treatment alone also modulated these
      transcription factors and ERK1/2 activation, the addition of glucocorticoids to
      MW samples resulted in a greater than additive reduction in the transcription
      factors and significant hyperactivation of LPS-induced ERK1/2 phosphorylation.
      ERK inhibitors reversed MW and MW plus corticosterone inhibition of LPS-induced
      IL-12p40. The potentiating effects of glucocorticoids were non-genomic because
      nuclear translocation of glucocorticoid receptor was not significantly different
      between MW and corticosterone treatment. This study demonstrates for the first
      time that MW and glucocorticoids independently modulate IL-12p40 production
      through a mechanism involving ERK1/2 hyperactivation and that glucocorticoids can
      significantly augment MW-induced inhibition of IL-12p40.

PMID- 21730056
TI  - Phylogenetic comparison of small RNA-triggered transcriptional gene silencing.
AB  - The discovery of RNA interference has revealed complex roles for small RNAs in
      regulating gene expression and cellular physiology. Small RNAs have been
      demonstrated to be involved in post-transcriptional suppression of translation,
      targeted degradation of messenger RNAs, and transcriptional suppression via
      epigenetic modifications of histones and DNA. In fission yeast, RNAi mediates
      suppression of centromeric transcripts, whereas in plants, transcriptional gene
      silencing appears to be primarily an antiviral mechanism. In mammals, the well
      annotated functional role of RNAi is primarily post-transcriptional, but there is
      increasing evidence that this mechanism can also work to suppress or modulate
      gene transcription, although it is not clear what primary function this serves.
      We overview, compare, and contrast the transcriptional silencing pathways in
      yeast, plants, and mammals in this article. This minireview is intended to
      provide the reader with a framework of how the RNAi machinery appears to be
      universally involved in various aspects of transcriptional regulation with
      discussions of similarities and differences in the components and mechanisms of
      achieving transcriptional silencing.

PMID- 21730057
TI  - A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin
      transporter dictates chloride-coupled neurotransmitter transport.
AB  - Na(+)- and Cl(-)-dependent uptake of neurotransmitters via transporters of the
      SLC6 family, including the human serotonin transporter (SLC6A4), is critical for
      efficient synaptic transmission. Although residues in the human serotonin
      transporter involved in direct Cl(-) coordination of human serotonin transport
      have been identified, the role of Cl(-) in the transport mechanism remains
      unclear. Through a combination of mutagenesis, chemical modification, substrate
      and charge flux measurements, and molecular modeling studies, we reveal an
      unexpected role for the highly conserved transmembrane segment 1 residue Asn-101
      in coupling Cl(-) binding to concentrative neurotransmitter uptake.

PMID- 21730058
TI  - A novel role of endothelin-1 in linking Toll-like receptor 7-mediated
      inflammation to fibrosis in congenital heart block.
AB  - Autoimmune associated congenital heart block (CHB) may result from pathogenic
      cross-talk between inflammatory and profibrosing pathways. Incubation of
      macrophages with immune complexes (IC) composed of Ro60, a target of the
      pathologic maternal autoantibodies necessary for CHB, hY3 ssRNA, and affinity
      purified anti-Ro60 antibody induces the Toll-like receptor 7 (TLR7)-dependent
      generation of supernatants that provoke a fibrosing phenotype in human fetal
      cardiac fibroblasts. We show herein that these cells are a major source of
      TGFbeta and that endothelin-1 (ET-1) is one of the key components responsible for
      the profibrosing effects generated by stimulated macrophages. Supernatants from
      macrophages incubated with IC induced the fibroblast secretion of TGFbeta, which
      was inhibited by treating the macrophages with an antagonist of TLR7. Under the
      same conditions, the induced fibroblast secretion of TGFbeta was decreased by
      inhibitors of the ET-1 receptors ETa or ETb or by an anti-ET-1 antibody but not
      by an isotype control. Exogenous ET-1 induced a profibrosing phenotype, whereas
      fibroblasts transfected with either ETa or ETb siRNA were unresponsive to the
      profibrosing effects of the IC-generated macrophage supernatants.
      Immunohistochemistry of the hearts from two fetuses dying with CHB revealed the
      presence of ET-1-producing mononuclear cells in the septal region in areas of
      calcification and fibrosis. In conclusion, these data support a novel role of ET
      1 in linking TLR7 inflammatory signaling to subsequent fibrosis and provide new
      insight in considering therapeutics for CHB.

PMID- 21730059
TI  - The protein Dredd is an essential component of the c-Jun N-terminal kinase
      pathway in the Drosophila immune response.
AB  - The Drosophila immune deficiency (IMD) pathway mobilizes c-Jun N-terminal kinase
      (JNK), caspase, and nuclear factor-kappaB (NF-kappaB) modules to counter
      infection with gram-negative bacteria. Dredd is an essential caspase in the IMD
      pathway, and it is widely established that NF-kappaB activation depends on Dredd.
      More recent cell culture studies suggested a role for Dredd in the activation of
      dJNK (Drosophila JNK). However, there are no epistatic or mechanistic data on the
      involvement of Dredd in dJNK activation. More importantly, there is no in vivo
      evidence to demonstrate a physiological requirement for Dredd in the IMD/dJNK
      pathway. We performed a comprehensive analysis of the role of Dredd in the
      IMD/dJNK pathway, and we demonstrated that Dredd is essential for the activation
      of IMD/dJNK in cell culture. We positioned Dredd activity at an early point of
      the IMD/dJNK pathway and uncovered a series of interactions between Dredd and
      additional proximal IMD pathway molecules. Mechanistically, we showed that the
      caspase activity inhibitor p35 blocked dJNK activation and the induction of dJNK
      dependent genes in cell culture and in vivo. Most importantly, we demonstrated
      that dredd mutant flies are completely inhibited in their ability to activate
      dJNK or express dJNK-responsive target genes after bacterial infection in vivo.
      In conclusion, we established Dredd as an essential component of the IMD pathway
      required for the full activation of IMD/dJNK in cell culture and in vivo. Our
      data enhance our appreciation of Dredd-dependent IMD signal transduction events.

PMID- 21730060
TI  - An early event in the transport mechanism of LacY protein: interaction between
      helices V and I.
AB  - Helix V in LacY, which abuts and crosses helix I in the N-terminal helix bundle
      of LacY, contains Arg(144) and Trp(151), two residues that play direct roles in
      sugar recognition and binding, as well as Cys(154), which is important for
      conformational flexibility. In this study, paired Cys replacement mutants in
      helices V and I were strategically constructed with tandem factor Xa protease
      cleavage sites in the loop between the two helices to test cross-linking. None of
      the mutants form disulfides spontaneously; however, three mutants (Pro(28) ->
      Cys/Cys(154), Pro(28) -> Cys/Val(158) -> Cys, and Phe(29) -> Cys/Val(158) -> Cys)
      exhibit cross-linking after treatment with copper/1,10-phenanthroline (Cu/Ph) or
      1,1-methanediyl bismethanethiosulfonate ((MTS)(2)-1), 3-4 A), and cross-linking
      is quantitative in the presence of ligand. Remarkably, with one mutant, complete
      cross-linking with (MTS)(2)-1 has no effect on lactose transport, whereas
      quantitative disulfide cross-linking catalyzed by Cu/Ph markedly inhibits
      transport activity. The findings are consistant with a number of previous
      conclusions suggesting that sugar binding to LacY causes a localized scissors
      like movement between helices V and I near the point where the two helices cross
      in the middle of the membrane. This ligand-induced movement may act to initiate
      the global conformational change resulting from sugar binding.

PMID- 21730061
TI  - Solution structure of the Mycobacterium tuberculosis EsxG.EsxH complex:
      functional implications and comparisons with other M. tuberculosis Esx family
      complexes.
AB  - Mycobacterium tuberculosis encodes five type VII secretion systems that are
      responsible for exporting a number of proteins, including members of the Esx
      family, which have been linked to tuberculosis pathogenesis and survival within
      host cells. The gene cluster encoding ESX-3 is regulated by the availability of
      iron and zinc, and secreted protein products such as the EsxG.EsxH complex have
      been associated with metal ion acquisition. EsxG and EsxH have previously been
      shown to form a stable 1:1 heterodimeric complex, and here we report the solution
      structure of the complex, which features a core four-helix bundle decorated at
      both ends by long, highly flexible, N- and C-terminal arms that contain a number
      of highly conserved residues. Despite clear similarities in the overall backbone
      fold to the EsxA.EsxB complex, the structure reveals some striking differences in
      surface features, including a potential protein interaction site on the surface
      of the EsxG.EsxH complex. EsxG.EsxH was also found to contain a specific Zn(2+)
      binding site formed from a cluster of histidine residues on EsxH, which are
      conserved across obligate mycobacterial pathogens including M. tuberculosis and
      Mycobacterium leprae. This site may reflect an essential role in zinc ion
      acquisition or point to Zn(2+)-dependent regulation of its interaction with
      functional partner proteins. Overall, the surface features of both the EsxG.EsxH
      and the EsxA.EsxB complexes suggest functions mediated via interactions with one
      or more target protein partners.

PMID- 21730062
TI  - Neuronal brain-derived neurotrophic factor is synthesized in excess, with levels
      regulated by sortilin-mediated trafficking and lysosomal degradation.
AB  - Brain-derived neurotrophic factor (BDNF) regulates neuronal differentiation,
      synaptic plasticity, and morphology, and modest changes in BDNF levels results in
      complex behavioral phenotypes. BDNF levels and intracellular localization in
      neurons are regulated by multiple mechanisms, including use of distinct
      promoters, mRNA and protein transport, and regulated cleavage of proBDNF to
      mature BDNF. Sortilin is an intracellular chaperone that binds to the prodomain
      of BDNF to traffic it to the regulated secretory pathway. However, sortilin binds
      to numerous ligands and plays a major role in mannose 6-phosphate receptor
      independent transport of lysosomal hydrolases utilizing motifs in the
      intracellular domain that mediate trafficking from the Golgi and late endosomes.
      Sortilin is modified by ectodomain shedding, although the biological implications
      of this are not known. Here we demonstrate that ADAM10 is the preferred protease
      to cleave sortilin in the extracellular stalk region, to release the ligand
      binding sortilin ectodomain from the transmembrane and cytoplasmic domains. We
      identify sortilin shedding at the cell surface and in an intracellular
      compartment. Both sortilin and BDNF are trafficked to and degraded by the
      lysosome in neurons, and this is dependent upon the sortilin cytoplasmic tail.
      Indeed, expression of the sortilin ectodomain, which corresponds to the domain
      released after shedding, impairs lysosomal targeting and degradation of BDNF.
      These findings characterize the regulation of sortilin shedding and identify a
      novel mechanism by which sortilin ectodomain shedding acts as a regulatory switch
      for delivery of BDNF to the secretory pathway or to the lysosome, thus modulating
      the bioavailability of endogenous BDNF.

PMID- 21730063
TI  - Calcineurin selectively docks with the dynamin Ixb splice variant to regulate
      activity-dependent bulk endocytosis.
AB  - Depolarization of nerve terminals stimulates rapid dephosphorylation of two
      isoforms of dynamin I (dynI), mediated by the calcium-dependent phosphatase
      calcineurin (CaN). Dephosphorylation at the major phosphorylation sites Ser
      774/778 promotes a dynI-syndapin I interaction for a specific mode of synaptic
      vesicle endocytosis called activity-dependent bulk endocytosis (ADBE). DynI has
      two main splice variants at its extreme C terminus, long or short (dynIxa and
      dynIxb) varying only by 20 (xa) or 7 (xb) residues. Recombinant GST fusion
      proteins of dynIxa and dynIxb proline-rich domains (PRDs) were used to pull down
      interacting proteins from rat brain nerve terminals. Both bound equally to
      syndapin, but dynIxb PRD exclusively bound to the catalytic subunit of CaNA,
      which recruited CaNB. Binding of CaN was increased in the presence of calcium and
      was accompanied by further recruitment of calmodulin. Point mutations showed that
      the entire C terminus of dynIxb is a CaN docking site related to a conserved CaN
      docking motif (PXIXI(T/S)). This sequence is unique to dynIxb among all other
      dynamin variants or genes. Peptide mimetics of the dynIxb tail blocked CaN
      binding in vitro and selectively inhibited depolarization-evoked dynI
      dephosphorylation in nerve terminals but not of other dephosphins. Therefore,
      docking to dynIxb is required for the regulation of both dynI splice variants,
      yet it does not regulate the phosphorylation cycle of other dephosphins. The
      peptide blocked ADBE, but not clathrin-mediated endocytosis of synaptic vesicles.
      Our results indicate that Ca(2+) influx regulates assembly of a fully active CaN
      calmodulin complex selectively on the tail of dynIxb and that the complex is
      recruited to sites of ADBE in nerve terminals.

PMID- 21730064
TI  - Resolving the function of distinct Munc18-1/SNARE protein interaction modes in a
      reconstituted membrane fusion assay.
AB  - Sec1p/Munc18 proteins and SNAP receptors (SNAREs) are key components of the
      intracellular membrane fusion machinery. Compartment-specific v-SNAREs on a
      transport vesicle pair with their cognate t-SNAREs on the target membrane and
      drive lipid bilayer fusion. In a reconstituted assay that dissects the sequential
      assembly of t-SNARE (syntaxin 1.SNAP-25) and v-/t-SNARE (VAMP2.syntaxin 1.SNAP
      25) complexes, and finally measures lipid bilayer merger, we resolved the
      inhibitory and stimulatory functions of the Sec1p/Munc18 protein Munc18-1 at the
      molecular level. Inhibition of membrane fusion by Munc18-1 requires a closed
      conformation of syntaxin 1. Remarkably, the concurrent preincubation of Munc18-1
      inhibited syntaxin 1 liposomes with both VAMP2 liposomes and SNAP-25 at low
      temperature releases the inhibition and effectively stimulates membrane fusion.
      VAMP8 liposomes can neither release the inhibition nor exert the stimulatory
      effect, demonstrating the need for a specific Munc18-1/VAMP2 interaction. In
      addition, Munc18-1 binds to the N-terminal peptide of syntaxin 1, which is
      obligatory for a robust stimulation of membrane fusion. In contrast, this
      interaction is neither required for the inhibitory function of Munc18-1 nor for
      the release of this block. These results indicate that Munc18-1 and the neuronal
      SNAREs already have the inherent capability to function as a basic stage-specific
      off/on switch to control membrane fusion.

PMID- 21730065
TI  - CXCR7/CXCR4 heterodimer constitutively recruits beta-arrestin to enhance cell
      migration.
AB  - G protein-coupled receptor hetero-oligomerization is emerging as an important
      regulator of ligand-dependent transmembrane signaling, but precisely how receptor
      heteromers affect receptor pharmacology remains largely unknown. In this study,
      we have attempted to identify the functional significance of the heteromeric
      complex between CXCR4 and CXCR7 chemokine receptors. We demonstrate that co
      expression of CXCR7 with CXCR4 results in constitutive recruitment of beta
      arrestin to the CXCR4.CXCR7 complex and simultaneous impairment of G(i)-mediated
      signaling. CXCR7/CXCR4 co-expression also results in potentiation of CXCL12 (SDF
      1)-mediated downstream beta-arrestin-dependent cell signaling pathways, including
      ERK1/2, p38 MAPK, and SAPK as judged from the results of experiments using siRNA
      knockdown to deplete beta-arrestin. Interestingly, CXCR7/CXCR4 co-expression
      enhances cell migration in response to CXCL12 stimulation. Again, inhibition of
      beta-arrestin using either siRNA knockdown or a dominant negative mutant
      abrogates the enhanced CXCL12-dependent migration of CXCR4/CXCR7-expressing
      cells. These results show how CXCR7, which cannot signal directly through G
      protein-linked pathways, can nevertheless affect cellular signaling networks by
      forming a heteromeric complex with CXCR4. The CXCR4.CXCR7 heterodimer complex
      recruits beta-arrestin, resulting in preferential activation of beta-arrestin
      linked signaling pathways over canonical G protein pathways. CXCL12-dependent
      signaling of CXCR4 and its role in cellular physiology, including cancer
      metastasis, should be evaluated in the context of potential functional hetero
      oligomerization with CXCR7.

PMID- 21730066
TI  - RNA folding in transcription elongation complex: implication for transcription
      termination.
AB  - Intrinsic transcription termination signal in DNA consists of a short inverted
      repeat followed by a T-rich stretch. Transcription of this sequence by RNA
      polymerase (RNAP) results in formation of a "termination hairpin" (TH) in the
      nascent RNA and in rapid dissociation of the transcription elongation complex
      (EC) at termination points located 7-8 nt downstream of the base of TH stem. RNAP
      envelops 15 nt of the RNA following RNA growing 3'-end, suggesting that folding
      of the TH is impeded by a tight protein environment when RNAP reaches the
      termination points. To monitor TH folding under this constraint, we halted
      Escherichia coli ECs at various distances downstream from a TH and treated them
      with single-strand specific RNase T1. The EC interfered with TH formation when
      halted at 6, 7, and 8, but not 9, nt downstream from the base of the potential
      stem. Thus, immediately before termination, the downstream arm of the TH is
      protected from complementary interactions with the upstream arm. This protection
      makes TH folding extremely sensitive to the sequence context, because the
      upstream arm easily engages in competing interactions with the rest of the
      nascent RNA. We demonstrate that by de-synchronizing TH formation and
      transcription of the termination points, this subtle competition significantly
      affects the efficiency of transcription termination. This finding can explain
      previous puzzling observations that sequences far upstream of the TH or point
      mutations in the terminator that preserve TH stability affect termination. These
      results can help understand other time sensitive co-transcriptional processes in
      pro- and eukaryotes.

PMID- 21730067
TI  - Peroxisomes are involved in biotin biosynthesis in Aspergillus and Arabidopsis.
AB  - Among the eukaryotes only plants and a number of fungi are able to synthesize
      biotin. Although initial events leading to the biosynthesis of biotin remain
      largely unknown, the final steps are known to occur in the mitochondria. Here we
      deleted the Aopex5 and Aopex7 genes encoding the receptors for peroxisomal
      targeting signals PTS1 and PTS2, respectively, in the filamentous fungus
      Aspergillus oryzae. In addition to exhibiting defects in the peroxisomal
      targeting of either PTS1 or PTS2 proteins, the deletion strains also displayed
      growth defects on minimal medium containing oleic acid as the sole carbon source.
      Unexpectedly, these peroxisomal transport-deficient strains also exhibited growth
      defects on minimal medium containing glucose as the sole carbon source that were
      remediated by the addition of biotin and its precursors, including 7-keto-8
      aminopelargonic acid (KAPA). Genome database searches in fungi and plants
      revealed that BioF protein/KAPA synthase, one of the biotin biosynthetic enzymes,
      has a PTS1 sequence at the C terminus. Fungal DeltabioF strains expressing the
      fungal and plant BioF proteins lacking PTS1 still exhibited growth defects in the
      absence of biotin, indicating that peroxisomal targeting of KAPA synthase is
      crucial for the biotin biosynthesis. Furthermore, in the plant Arabidopsis
      thaliana, AtBioF localized to the peroxisomes through recognition of its PTS1
      sequence, suggesting involvement of peroxisomes in biotin biosynthesis in plants.
      Taken together we demonstrate a novel role for peroxisomes in biotin biosynthesis
      and suggest the presence of as yet unidentified peroxisomal proteins that
      function in the earlier steps of biotin biosynthesis.

PMID- 21730068
TI  - Structural determinants of discrimination of NAD+ from NADH in yeast
      mitochondrial NADH kinase Pos5.
AB  - NAD kinase catalyzes the phosphorylation of NAD(+) to synthesize NADP(+), whereas
      NADH kinase catalyzes conversion of NADH to NADPH. The mitochondrial protein Pos5
      of Saccharomyces cerevisiae shows much higher NADH kinase than NAD kinase
      activity and is therefore referred to as NADH kinase. To clarify the structural
      determinant underlying the high NADH kinase activity of Pos5 and its selectivity
      for NADH over NAD(+), we determined the tertiary structure of Pos5 complexed with
      NADH at a resolution of 2.0 A. Detailed analysis, including a comparison of the
      tertiary structure of Pos5 with the structures of human and bacterial NAD
      kinases, revealed that Arg-293 of Pos5, corresponding to His-351 of human NAD
      kinase, confers a positive charge on the surface of NADH-binding site, whereas
      the corresponding His residue does not. Accordingly, conversion of the Arg-293
      into a His residue reduced the ratio of NADH kinase activity to NAD kinase
      activity from 8.6 to 2.1. Conversely, simultaneous changes of Ala-330 and His-351
      of human NAD kinase into Ser and Arg residues significantly increased the ratio
      of NADH kinase activity to NAD kinase activity from 0.043 to 1.39; human Ala-330
      corresponds to Pos5 Ser-272, which interacts with the side chain of Arg-293. Arg
      293 and Ser-272 were highly conserved in Pos5 homologs (putative NADH kinases),
      but not in putative NAD kinases. Thus, Arg-293 of Pos5 is a major determinant of
      NADH selectivity. Moreover, Ser-272 appears to assist Arg-293 in achieving the
      appropriate conformation.

PMID- 21730069
TI  - STAT3 protein promotes T-cell survival and inhibits interleukin-2 production
      through up-regulation of Class O Forkhead transcription factors.
AB  - Much is known about the role of STAT3 in regulating differentiation of
      interleukin-17-producing Th17 cells, but its function in other lymphocyte subsets
      is not well understood. In this report, we reveal wide-ranging functions of STAT3
      in T-cells and provide evidence that STAT3 is convergence point for mechanisms
      that regulate lymphocyte quiescence and those controlling T-cell activation and
      survival. We show here that STAT3 inhibits T-lymphocyte proliferation by up
      regulating the expression of Class-O Forkhead transcription factors, which play
      essential roles in maintaining T-cells in quiescent state. We further show that
      STAT3 binds directly to FoxO1 or FoxO3a promoter and that STAT3-deficiency
      resulted in down-regulation of the expression of FoxO1, FoxO3a and FoxO-target
      genes (IkappaB and p27Kip1). Compared with wild-type T-cells, STAT3-deficient T
      cells produced more IL-2, due in part, to marked decrease in IkappaB-mediated
      sequestration of NF-kappaB in the cytoplasm and resultant enhancement of NF
      kappaB activation. However, the high level of IL-2 production by STAT3-deficient
      T-cells was partially restored to normal levels by overexpressing FoxO1. It is
      notable that their exaggerated increase in IL-2 production rendered STAT3
      deficient lymphocytes more susceptible to activation-induced cell death,
      suggesting that STAT3 might protect T-cells from apoptosis by limiting their
      production of IL-2 through up-regulation of FoxO1/FoxO3a expression. Moreover, we
      found that STAT3 enhanced survival of activated T-cells by up-regulating OX-40
      and Bcl-2 while down-regulating FasL and Bad expression, suggesting that similar
      to role of FoxOs in regulating the lifespan of worms, STAT3 and FoxO pathways
      converge to regulate lifespan of T-lymphocytes.

PMID- 21730070
TI  - A molecular mechanism for copper transportation to tyrosinase that is assisted by
      a metallochaperone, caddie protein.
AB  - The Cu(II)-soaked crystal structure of tyrosinase that is present in a complex
      with a protein, designated "caddie," which we previously determined, possesses
      two copper ions at its catalytic center. We had identified two copper-binding
      sites in the caddie protein and speculated that copper bound to caddie may be
      transported to the tyrosinase catalytic center. In our present study, at a 1.16
      1.58 A resolution, we determined the crystal structures of tyrosinase complexed
      with caddie prepared by altering the soaking time of the copper ion and the
      structures of tyrosinase complexed with different caddie mutants that display
      little or no capacity to activate tyrosinase. Based on these structures, we
      propose a molecular mechanism by which two copper ions are transported to the
      tyrosinase catalytic center with the assistance of caddie acting as a
      metallochaperone.

PMID- 21730071
TI  - Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that
      resist aging.
AB  - The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase, are
      primary targets of organophosphates (OPs). Exposure to OPs can lead to serious
      cardiovascular complications, respiratory compromise, and death. Current therapy
      to combat OP poisoning involves an oxime reactivator (2-PAM, obidoxime, TMB4, or
      HI-6) combined with atropine and on occasion an anticonvulsant.
      Butyrylcholinesterase, administered in the plasma compartment as a bio-scavenger,
      has also shown efficacy but is limited by its strict stoichiometric scavenging,
      slow reactivation, and a propensity for aging. Here, we characterize 10 human (h)
      AChE mutants that, when coupled with an oxime, give rise to catalytic
      reactivation and aging resistance of the soman conjugate. With the most efficient
      human AChE mutant Y337A/F338A, we show enhanced reactivation rates for several OP
      hAChE conjugates compared with wild-type hAChE when reactivated with HI-6 (1-(2'
      hydroxyiminomethyl-1'-pyridinium)-3-(4'-carbamoyl-1-pyridinium)). In addition, we
      interrogated an 840-member novel oxime library for reactivation of Y337A/F338A
      hAChE-OP conjugates to delineate the most efficient oxime-mutant enzyme pairs for
      catalytic bio-scavenging. Combining the increased accessibility of the Y337A
      mutation to oximes within the space-impacted active center gorge with the aging
      resistance of the F338A mutation provides increased substrate diversity in
      scavenging potential for aging-prone alkyl phosphate inhibitors.

PMID- 21730072
TI  - TLR4 protein contributes to cigarette smoke-induced matrix metalloproteinase-1
      (MMP-1) expression in chronic obstructive pulmonary disease.
AB  - Cigarette smoke is the major risk factor associated with the development of
      chronic obstructive pulmonary disease and alters expression of proteolytic
      enzymes that contribute to disease pathology. Previously, we reported that smoke
      exposure leads to the induction of matrix metalloproteinase-1 (MMP-1) through the
      activation of ERK1/2, which is critical to the development of emphysema. To date,
      the upstream signaling pathway by which cigarette smoke induces MMP-1 expression
      has been undefined. This study demonstrates that cigarette smoke mediates MMP-1
      expression via activation of the TLR4 signaling cascade. In vitro cell culture
      studies demonstrated that cigarette smoke-induced MMP-1 was regulated by TLR4 via
      MyD88/IRAK1. Blockade of TLR4 or inhibition of IRAK1 prevented cigarette smoke
      induction of MMP-1. Mice exposed to acute levels of cigarette smoke exhibited
      increased TLR4 expression. To further confirm the in vivo relevance of this
      signaling pathway, rabbits exposed to acute cigarette smoke were found to have
      elevated TLR4 signaling and subsequent MMP-1 expression. Additionally, lungs from
      smokers exhibited elevated TLR4 and MMP-1 levels. Therefore, our data indicate
      that TLR4 signaling, through MyD88 and IRAK1, plays a predominant role in MMP-1
      induction by cigarette smoke. The identification of the TLR4 pathway as a
      regulator of smoke-induced protease production presents a series of novel targets
      for future therapy in chronic obstructive pulmonary disease.

PMID- 21730073
TI  - Sox factors transcriptionally regulate ROBO4 gene expression in developing
      vasculature in zebrafish.
AB  - Despite their importance as members of the Roundabout (Robo) family in the
      control of axonal and vascular patterning, the transcriptional regulation of
      these genes is poorly understood. In this study, we show that members of the Sry
      related high mobility box (Sox) transcription factor family as being
      transcriptional regulators of roundabout4 (robo4), a Robo gene family member that
      participates in sprouting angiogenesis in vivo, in zebrafish. Double whole mount
      in situ hybridization analysis in zebrafish embryos revealed co-localization of
      the vascular relevant Sox factors sox7 or sox18 mRNA with robo4 transcripts in
      developing intersomitic vessels. A 3-kb human ROBO4 promoter element was able to
      drive reporter expression in zebrafish to recapitulate the endogenous temporal
      intersomitic vessel expression pattern of robo4. EMSA analysis confirmed binding
      of Sox18 to a canonical Sox binding site (from -1170 bp to -1176 bp) in the ROBO4
      promoter (3 kb), and mutation analysis indicated that this site was partially
      responsible for ROBO4 promoter activity in ECs. A combination of gain- and loss
      of-function analysis identified Sox7 and Sox18 co-regulation of robo4 but not
      fli1a transcripts in zebrafish. Finally, Sox-mediated robo4 transcriptional
      regulation is conserved across evolution. These studies imply Sox-mediated
      transcriptional regulation of Robo4 in the developing embryonic vasculature.

PMID- 21730074
TI  - Interaction of RNA polymerase II fork loop 2 with downstream non-template DNA
      regulates transcription elongation.
AB  - Fork loop 2 is a small semiconservative segment of the larger fork domain in the
      second largest Rpb2 subunit of RNA polymerase II (Pol II). This flexible loop,
      juxtaposed at the leading edge of transcription bubble, has been proposed to
      participate in DNA strand separation, translocation along DNA, and NTP loading to
      Pol II during elongation. Here we show that the Rpb2 mutant carrying a deletion
      of the flexible part of the loop is not lethal in yeast. The mutation exhibits no
      defects in DNA melting and translocation in vitro but confers a moderate decrease
      of the catalytic activity of the enzyme caused by the impaired sequestration of
      the NTP substrate in the active center prior to catalysis. In the structural
      model of the Pol II elongation complex, fork loop 2 directly interacts with an
      unpaired DNA residue in the non-template DNA strand one nucleotide ahead from the
      active center (the i+2 position). We showed that elimination of this putative
      interaction by replacement of the i+2 residue with an abasic site inhibits Pol II
      activity to the same degree as the deletion of fork loop 2. This replacement has
      no detectable effect on the activity of the mutant enzyme. We provide direct
      evidence that interaction of fork loop 2 with the non-template DNA strand
      facilitates NTP sequestration through interaction with the adjacent segment of
      the fork domain involved in the active center of Pol II.

PMID- 21730075
TI  - Beyond the 3+3 method: expanded algorithms for dose- escalation in Phase I
      oncology trials of two agents.
AB  - BACKGROUND: The number of published Phase I trials for determining a maximum
      tolerated combination of two agents is increasing, with a majority of those
      trials suffering from poor study design. A recent editorial proposed a 3+3+3
      design, which takes the traditional 3+3 design used for one-agent dose-finding
      and adds an additional possible cohort of three patients. PURPOSE: To investigate
      the utility and performance of the 3+3+3, and more generally, A+B+C algorithmic
      designs, in Phase I trials of two-agent combinations and to discuss the issues
      related to such designs. METHODS: Operating characteristics for an A+B+C design
      can be computed exactly in the statistical software package R using publicly
      available functions created by the authors. Using those functions, six different
      A+B+C designs are compared in six different settings with respect to the dose
      limiting toxicity rate of combinations that each design selects as the maximum
      tolerated combination, as well as the average total number of patients required
      by each design and the average number of patients assigned to each combination.
      RESULTS: Allowing for simultaneous escalation of doses of both agents does not
      increase patients' exposure to overly toxic combinations, yet increases the
      probability of identifying the maximum tolerated combination when it occurs at
      higher doses of either agent, than a design that forbids simultaneous escalation.
      Designs in which A <= 3 tend to target combinations with dose-limiting toxicity
      rates higher than designs in which A >= 4. LIMITATIONS: The implicitly targeted
      dose-limiting toxicity rate of any given algorithmic design is not transparent,
      requiring computation of results under a variety of settings to help understand
      the operating characteristics of that design. Thus, the appropriate A+B+C design
      will vary from trial to trial. A+B+C designs also have 'short memory', as
      escalation decisions are based primarily on the most recent cohort of patients.
      CONCLUSIONS: Algorithmic A+B+C designs are potentially useful in the design of
      Phase I trials of combinations of two agents. However, a head-to-head comparison
      to model-based designs is needed to warrant their general use.

PMID- 21730076
TI  - How to use marginal structural models in randomized trials to estimate the
      natural direct and indirect effects of therapies mediated by causal
      intermediates.
AB  - BACKGROUND: Although intention-to-treat analysis is a standard approach,
      additional supplemental analyses are often required to evaluate the biological
      relationship among interventions, intermediates, and outcomes. Therefore, we need
      to evaluate whether the effect of an intervention on a particular outcome is
      mediated by a hypothesized intermediate variable. PURPOSE: To evaluate the size
      of the direct effect in the total effect, we applied the marginal structural
      model to estimate the average natural direct and indirect effects in a large
      scale randomized controlled trial (RCT). Method The average natural direct effect
      is defined as the difference in the probability of a counterfactual outcome
      between the experimental and control arms, with the intermediate set to what it
      would have been, had the intervention been a control treatment. We considered two
      marginal structural models to estimate the average natural direct and indirect
      effects introduced by VanderWeele (Epidemiology 2009) and applied them in a large
      scale RCT - the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J
      trial) - that compared angiotensin receptor blockers and calcium-channel blockers
      in high-risk hypertensive patients. RESULTS: There were no strong blood pressure
      independent or dependent effects; however, a systolic blood pressure reduction of
      about 1.9  mmHg suppressed all events. Compared to the blood pressure-independent
      effects of calcium channel blockers, those of angiotensin receptor blockers
      contributed positively to cardiovascular and cardiac events, but negatively to
      cerebrovascular events. LIMITATIONS: There is a particular condition for
      estimating the average natural direct effect. It is impossible to check whether
      this condition is satisfied with the available data. CONCLUSION: We estimated the
      average natural direct and indirect effects through the achieved systolic blood
      pressure in the CASE-J trial. This first application of estimating the average
      natural effects in an RCT can be useful for obtaining an in-depth understanding
      of the results and further development of similar interventions.

PMID- 21730077
TI  - The 6-MP versus placebo clinical trial in acute leukemia.
AB  - BACKGROUND: This article gives the status of clinical cancer research in the
      1950's-1960's and tells the story of the development and conduct of the 6
      mercaptopurine (6-MP) versus placebo clinical trial in acute leukemia through the
      initiation, design, conduct and analysis stages, with emphasis on the ethical
      aspects of randomizing patients to 6-MP or placebo when in remission. PURPOSE:
      The specific objective was to compare the lengths of remission for patients
      receiving 6-MP or placebo after achieving complete or partial remission from
      steroid treatment. METHODS: A randomized, double-blind, placebo controlled
      sequential study was conducted in which patients were paired by remission status
      at each of the eleven institutions participating in the study, and randomized to
      6-MP or placebo within each pair of patients. A preference for 6-MP or placebo
      was recorded depending on which patient in the pair had the longer remission. The
      preferences were plotted according to a restricted sequential procedure devised
      by Peter Armitage and, depending on which boundary of the design was crossed, a
      statistically significant difference could be declared favoring 6-MP, placebo or
      no preference. CONCLUSIONS: The trial established the efficacy of 6-MP for
      maintaining longer remissions in acute leukemia and led to the concept of
      'adjuvant chemotherapy', namely that patients with minimal disease have a
      substantially better response to chemotherapy than patients with advanced
      disease, a concept that has been followed in many other forms of cancer.
      Statistically, the fact that many patients were still in remission when the study
      was stopped (i.e. the length of remission data for these patients was 'right
      censored') led to the development of a generalized Wilcoxon test and was an
      important influence on Cox's development of the proportional hazards model. The
      trial had an innovative design in the early 1960's and has been an important
      influence on subsequent clinical research in cancer and statistical research in
      survival analysis.

PMID- 21730078
TI  - Randomized controlled trial of a collaborative care intervention to manage cancer
      related symptoms: lessons learned.
AB  - BACKGROUND: Collaborative care interventions to treat depression have begun to be
      tested in settings outside of primary care. However, few studies have expanded
      the collaborative care model to other settings and targeted comorbid physical
      symptoms of depression. PURPOSE: The aims of this report were to: (1) describe
      the design and methods of a trial testing the efficacy of a stepped collaborative
      care intervention designed to manage cancer-related symptoms and improve overall
      quality of life in patients diagnosed with hepatobiliary carcinoma; and (2) share
      the lessons learned during the design, implementation, and evaluation of the
      trial. METHODS: The trial was a phase III randomized controlled trial testing the
      efficacy of a stepped collaborative care intervention to reduce depression, pain,
      and fatigue in patients diagnosed with advanced cancer. The intervention was
      compared to an enhanced usual care arm. The primary outcomes included the Center
      for Epidemiological Studies-Depression scale, Brief Pain Inventory, and
      Functional Assessment of Cancer Therapy (FACT)-Fatigue, and the FACT
      Hepatobiliary. Sociodemographic and disease-specific characteristics were
      recorded from the medical record; Natural Killer cells and cytokines that are
      associated with these symptoms and with disease progression were assayed from
      serum. RESULTS:   and  Discussion The issues addressed include: (1) development
      of collaborative care in the context of oncology (e.g., timing of the
      intervention, tailoring of the intervention, ethical issues regarding
      randomization of patients, and changes in medical treatment over the course of
      the study); (2) use of a website by chronically ill populations (e.g., design and
      access to the website, development of the website and intervention, ethical
      issues associated with website development, website usage, and unanticipated
      costs associated with website development); (3) evaluation of the efficacy of
      intervention (e.g., patient preferences, proxy raters, changes in medical
      treatment, and inclusion of biomarkers as endpoints); and (4) analyses and
      interpretation of the intervention (e.g., confounding factors, dose and active
      ingredients, and risks and benefits of collaborative care interventions in
      chronically ill patients). LIMITATIONS: The limitations to the study, although
      not fully realized at this time as the trial is ongoing, include: (1)
      heterogeneity of the diagnoses and treatments of participants; and (2) inclusion
      of caregivers as proxy raters but not as participants in the intervention.
      CONCLUSIONS: Collaborative care interventions to manage multiple symptoms in a
      tertiary cancer center are feasible. However, researchers designing and
      implementing interventions that are web-based, target multiple symptoms, and for
      oncology patients may benefit from previous experiences.

PMID- 21730079
TI  - Redesigning a large school-based clinical trial in response to changes in
      community practice.
AB  - BACKGROUND: Asthma exacerbations are seasonal with the greatest risk in
      elementary-age students occurring shortly after returning to school following
      summer break. Recent research suggests that this seasonality in children is
      primarily related to viral respiratory tract infections. Regular hand washing is
      the most effective method to prevent the spread of viral respiratory infections;
      unfortunately, achieving hand washing recommendations in schools is difficult.
      Therefore, we designed a study to evaluate the effect of hand sanitizer use in
      elementary schools on exacerbations among children with asthma. PURPOSE: To
      describe the process of redesigning the trial in response to changes in the
      safety profile of the hand sanitizer as well as changes in hand hygiene practice
      in the schools. METHODS: The original trial was a randomized, longitudinal,
      subject-blinded, placebo-controlled, community-based crossover trial. The primary
      aim was to evaluate the incremental effectiveness of hand sanitizer use in
      addition to usual hand hygiene practices to decrease asthma exacerbations in
      elementary-age children. Three events occurred that required major modifications
      to the original study protocol: (1) safety concerns arose regarding the hand
      sanitizer's active ingredient; (2) no substitute placebo hand sanitizer was
      available; and (3) community preferences changed regarding hand hygiene practices
      in the schools. RESULTS: The revised protocol is a randomized, longitudinal,
      community-based crossover trial. The primary aim is to evaluate the incremental
      effectiveness of a two-step hand hygiene process (hand hygiene education plus
      institutionally provided alcohol-based hand sanitizer) versus usual care to
      decrease asthma exacerbations. Enrollment was completed in May 2009 with 527
      students from 30 schools. The intervention began in August 2009 and will continue
      through May 2011. Study results should be available at the end of 2011.
      LIMITATIONS: The changed design does not allow us to directly measure the
      effectiveness of hand sanitizer use as a supplement to traditional hand washing
      practices. CONCLUSIONS: The need to balance a rigorous study design with one that
      is acceptable to the community requires investigators to be actively involved
      with community collaborators and able to adapt study protocols to fit changing
      community practices.

PMID- 21730081
TI  - Providing the results of research to participants: a mixed-method study of the
      benefits and challenges of a consultative approach.
AB  - BACKGROUND: How best to provide the findings of research to study participants
      remains poorly understood. PURPOSE: We aimed to develop, deliver, and evaluate a
      consultative approach to inform provision of feedback about research findings to
      participants in the Oracle Children Study (OCS). The OCS had identified adverse
      outcomes for some children whose mothers had been prescribed antibiotics as part
      of a trial in pregnancy. METHODS: An iterative process, including focus groups
      with OCS participants and consultation with other OCS stakeholders, was used to
      inform the development of a feedback package, including a results leaflet, for
      OCS participants. A questionnaire survey of participants' reactions to receiving
      the results leaflet was conducted. The Kolmogorov-Smirnov two-sample test was
      used to compare responses between different groups of respondents. Analysis of
      open-ended comments on the questionnaire was based on the constant comparative
      method. RESULTS: Three focus groups with study participants provided insight into
      the potential emotional impact of receiving the results and into how the results
      might most clearly be explained. Negotiations with other stakeholders identified
      other priorities, including the need for scientific credibility. These multiple
      needs had to be balanced. The results leaflet was posted to all 4676 UK OCS
      participants. Survey responses were received from 1124 (25%) of participants.
      They indicated that the feedback was mostly well received by participants. Those
      whose children were affected by conditions associated with increased risk from
      trial participation were more likely to experience emotional distress on
      receiving the trial results, but there was also evidence of some other
      unanticipated impacts. LIMITATIONS: This study is limited by the low response
      rate to the survey. CONCLUSIONS: Important lessons can be learned from using a
      consultative approach to developing feedback about research results for study
      participants. Especially where the findings are unwelcome, feedback development
      may involve methodological, ethical, emotional, and practical challenges, be
      resource-intensive, and need early planning.

PMID- 21730080
TI  - The development and description of the comparison group in the Look AHEAD trial.
AB  - BACKGROUND: Despite more lifestyle intervention trials, there is little published
      information on the development of the comparison group intervention. This article
      describes the comparison group intervention, termed Diabetes Support and
      Education Intervention and its development for the Action for HEAlth in Diabetes
      (Look AHEAD) trial. Look AHEAD, a randomized, controlled, multicenter trial, was
      designed to determine whether an Intensive Lifestyle Intervention to reduce
      weight and increase physical activity reduces cardiovascular morbidity and
      mortality in overweight volunteers with type 2 diabetes compared to the Diabetes
      Support and Education Intervention. The Diabetes Support and Education Committee
      was charged with developing the Diabetes Support and Education Intervention with
      the primary aim of participant retention. PURPOSE: The objectives were to design
      the Diabetes Support and Education Intervention sessions, standardize delivery
      across the 16 clinics, review quality and protocol adherence and advise on
      staffing and funding. METHODS: Following a mandatory session on basic diabetes
      education, three optional sessions were offered on nutrition, physical activity,
      and support yearly for 4 years. For each session, guidelines, objectives,
      activities, and a resource list were created. CONCLUSIONS: Participant
      evaluations were very positive with hands on experiences being the most valuable.
      Retention so far at years 1 and 4 has been excellent and only slightly lower in
      the Diabetes Support and Education Intervention arm. The comparison group plays
      an important role in the success of a clinical trial. Understanding the effort
      needed to develop and implement the comparison group intervention will facilitate
      its implementation in future lifestyle intervention trials, particularly
      multicenter trials. Retention rates may improve by developing the comparison
      intervention simultaneously with the lifestyle intervention.

PMID- 21730082
TI  - Monitoring the quality of conduct of clinical trials: a survey of current
      practices.
AB  - BACKGROUND: There is a little empirical evidence to determine which, if any,
      monitoring practices best achieve the goals of trial monitoring set forth in ICH
      E6 under the variable circumstances of different clinical trial settings.
      PURPOSE: The purpose of this project was to describe current methods of
      monitoring clinical trials and to explore the rationale for the use of those
      methods. METHODS: An electronic survey of known monitoring practices was
      developed and sent to over 200 organizations involved in conducting clinical
      research. The survey collected information on institutional demographics, methods
      of overall study oversight, use of risk-based monitoring and factors that
      influence assessments of risk, and details on quality assurance and monitoring
      practices. RESULTS: Seventy-nine organizations completed the survey; our analysis
      included the 65 organizations that indicated they perform clinical trials. Data
      from the survey indicate that a wide variety of monitoring practices are
      currently being employed. Eighty-three percent of respondents use centrally
      available data to evaluate site performance, but only 12% of respondents always
      or frequently used centralized monitoring to replace on-site visits. Eighty-seven
      percent of respondents indicated that they always performed on-site visits. This
      varied by type of organization, with 31% of academic coordinating
      centers/cooperative groups/government organizations always performing on-site
      monitoring visits versus 84% of other organizations. The rationale for using a
      specific monitoring approach does not appear to be based on empirical evidence.
      Fifty-four percent of respondents stated that 'usual practice' determined the
      frequency with which they conducted on-site monitoring visits. LIMITATIONS: The
      overall response rate to our survey was only 30%; thus, we may not have captured
      the full variance of current monitoring practices, and our responding sample may
      not be representative. CONCLUSION: These findings underscore the necessity of
      research to provide an evidence base for monitoring practice.

PMID- 21730083
TI  - Clinician-trialist rounds: 4. why not do an N-of-1 RCT?

PMID- 21730084
TI  - Investigations on the pattern recognition molecule M-ficolin: quantitative
      aspects of bacterial binding and leukocyte association.
AB  - M-ficolin is a PRM of the innate immune system, found in serum and associated
      with leukocytes. We used the soluble form to study specificity toward Gram
      positive bacteria and characterized and quantified cell-associated M-ficolin. The
      binding of M-ficolin to capsulated and noncapsulated strains of Streptococcus
      agalactiae (GBS) and Staphylococcus aureus was investigated. We did not observe
      binding of M-ficolin to any of 13 serotypes of S. aureus. Dose-dependent binding
      of M-ficolin was demonstrated for all of the capsulated GBS strains. The binding
      was abolished by prior treatment of the bacteria with sialidase, indicating that
      sialic acid is the ligand for M-ficolin on these bacteria. GlcNAc could inhibit
      the binding, suggesting that M-ficolin binds via its FBG. M-ficolin was found
      associated with the complement-activating enzyme in serum, and M-ficolin bound to
      GBS mediated activation of the complement system. M-ficolin expression on
      leukocytes was evaluated by flow cytometry with anti-M-ficolin mAb. Total M
      ficolin of different leukocytes was quantified in detergent extracts. Monocytes
      and granulocytes showed similar M-ficolin surface expression, 1.1 * 10(5) and 0.7
      * 10(5) M-ficolin molecules/cell, respectively. The total M-ficolin content of
      the cells was 1.5 * 10(6) molecules/monocyte and approximately one-third of this
      for granulocytes. Lymphocytes contained <1.5% of the amount estimated for
      monocytes, and none was revealed on the surface of lymphocytes by flow cytometry.
      Immunohistochemical analysis of the distribution of M-ficolin in 25 tissues
      revealed staining of only granulocytes and monocytes. Reported M-ficolin
      expression by type II pneumocytes could not be verified. We demonstrate the
      specific binding of M-ficolin to sialic acids in the capsule of GBS and give
      quantitative aspects of the cell-associated M-ficolin.

PMID- 21730085
TI  - Plasmacytoid dendritic cells and cancer.
AB  - Cancer develops in a complex microenvironment comprising cancer cells, stromal
      cells, and host immune cells with their soluble products. The counteracting host
      protective and tumor-promoting roles of different immune cell populations have
      been elegantly clarified in the last decade by pertinent genetically modified
      mouse models. Among cells with a potential role in cancer immunity, PDCs might
      represent important players as a result of their capacity to bring together
      innate and adaptive immunity. This review summarizes current knowledge about the
      role of PDCs in cancer immunity. PDCs have been documented in primary and
      metastatic human neoplasms; however, the clinical significance of this finding is
      still unknown. Once into the tumor bed, PDCs can be hijacked by the tumor
      microenvironment and lose their propensity to produce the required amount of
      endogenous I-IFN. However, when properly reprogrammed (i.e., by TLR agonists),
      PDCs might mediate tumor rejection in a clinical setting. Tumor rejection, at
      least partially, is driven by I-IFN and seems to require a cross-talk with other
      innate immune cells, including IFN DCs. The latter evidence, although still
      limited to skin cancers, can provide a leading model for developing adjuvant
      immune therapy for other neoplasms. To this end, the generation of appropriate
      mouse models to modulate the frequency and activation state of murine PDCs will
      also be of remarkable importance.

PMID- 21730086
TI  - Laboratory adaptation of Bordetella pertussis is associated with the loss of type
      three secretion system functionality.
AB  - Although Bordetella pertussis contains and transcribes loci encoding type III
      secretion system (TTSS) homologues, expression of TTSS-associated proteins has
      been reported only for non-laboratory-adapted Irish clinical isolates. Here we
      confirm such a result for clinical isolates obtained from patients treated in
      Argentinean hospitals. Moreover, we demonstrate that the expression of TTSS
      associated proteins is independent both of the year in which the isolate was
      obtained and of the types of polymorphic alleles for other virulence factors but
      is dependent on environmental growth conditions. Interestingly, we observed that
      TTSS-associated protein expression is lost after successive in vitro passages but
      becomes operative again when bacteria come into contact with the host. This in
      vivo activation of TTSS expression was observed not only for clinical isolates
      previously adapted to the laboratory after successive in vitro passages but also
      for vaccine strains that did not express the system in vitro. The reversibility
      of TTSS expression, demonstrated by its switching off-on when the bacterium comes
      into contact with the host, appears to be an adaptive response of this pathogen.

PMID- 21730087
TI  - Indoleamine 2,3-dioxygenase, tryptophan catabolism, and Mycobacterium avium
      subsp. paratuberculosis: a model for chronic mycobacterial infections.
AB  - Virulent mycobacterial infections progress slowly, with a latent period that
      leads to clinical disease in a proportion of cases. Mycobacterium avium subsp.
      paratuberculosis is an intracellular pathogen that causes paratuberculosis or
      Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3
      dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally
      reported to have a role in intracellular pathogen killing and has since been
      shown to have an important immunoregulatory role in chronic immune diseases. Here
      we demonstrate an association between increased IDO levels and progression to
      clinical mycobacterial disease in a natural host, characterizing gene expression,
      protein localization, and functional effects. IDO mRNA levels were significantly
      increased in M. avium subsp. paratuberculosis-infected monocytic cells. Levels of
      both IDO gene and protein expression were significantly upregulated within the
      affected tissues of sheep with JD, particularly at the site of primary infection,
      the ileum, of animals with severe multibacillary disease. Lesion severity was
      correlated with the level of IDO gene expression. IDO gene expression was also
      increased in the peripheral blood cells of M. avium subsp. paratuberculosis
      exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were
      functional, as shown by decreased plasma tryptophan levels, which correlated with
      the onset of clinical signs, a stage well known to be associated with Th1
      immunosuppression. IDO may be involved in downregulating immune responses to M.
      avium subsp. paratuberculosis and other virulent mycobacteria, which may be an
      example of the pathogen harnessing host immunoregulatory pathways to aid
      survival. These findings raise new questions about the host-mycobacterium
      interactions in the progression from latent to clinical disease.

PMID- 21730088
TI  - Potential role of fibroblast-like synoviocytes in joint damage induced by
      Brucella abortus infection through production and induction of matrix
      metalloproteinases.
AB  - Arthritis is one of the most common complications of human brucellosis, but its
      pathogenic mechanisms have not been elucidated. Fibroblast-like synoviocytes
      (FLS) are known to be central mediators of joint damage in inflammatory
      arthritides through the production of matrix metalloproteinases (MMPs) that
      degrade collagen and of cytokines and chemokines that mediate the recruitment and
      activation of leukocytes. In this study we show that Brucella abortus infects and
      replicates in human FLS (SW982 cell line) in vitro and that infection results in
      the production of MMP-2 and proinflammatory mediators (interleukin-6 [IL-6], IL
      8, monocyte chemotactic protein 1 [MCP-1], and granulocyte-macrophage colony
      stimulating factor [GM-CSF]). Culture supernatants from Brucella-infected FLS
      induced the migration of monocytes and neutrophils in vitro and also induced
      these cells to secrete MMP-9 in a GM-CSF- and IL-6-dependent fashion,
      respectively. Reciprocally, culture supernatants from Brucella-infected monocytes
      and neutrophils induced FLS to produce MMP-2 in a tumor necrosis factor alpha
      (TNF-alpha)-dependent fashion. The secretion of proinflammatory mediators and MMP
      2 by FLS did not depend on bacterial viability, since it was also induced by heat
      killed B. abortus (HKBA) and by a model Brucella lipoprotein (L-Omp19). These
      responses were mediated by the recognition of B. abortus antigens through Toll
      like receptor 2. The intra-articular injection of HKBA or L-Omp19 into the knee
      joint of mice resulted in the local induction of the proinflammatory mediators
      MMP-2 and MMP-9 and in the generation of a mixed inflammatory infiltrate. These
      results suggest that FLS, and phagocytes recruited by them to the infection
      focus, may be involved in joint damage during brucellar arthritis through the
      production of MMPs and proinflammatory mediators.

PMID- 21730089
TI  - Cholesterol depletion reduces entry of Campylobacter jejuni cytolethal distending
      toxin and attenuates intoxication of host cells.
AB  - Campylobacter jejuni is a common cause of pediatric diarrhea worldwide.
      Cytolethal distending toxin, produced by Campylobacter jejuni, is a putative
      virulence factor that induces cell cycle arrest and apoptosis in eukaryotic
      cells. Cellular cholesterol, a major component of lipid rafts, has a pivotal role
      in regulating signaling transduction and protein trafficking as well as pathogen
      internalization. In this study, we demonstrated that cell intoxication by
      Campylobacter jejuni cytolethal distending toxin is through the association of
      cytolethal distending toxin subunits and membrane cholesterol-rich microdomains.
      Cytolethal distending toxin subunits cofractionated with detergent-resistant
      membranes, while the distribution reduced upon the depletion of cholesterol,
      suggesting that cytolethal distending toxin subunits are associated with lipid
      rafts. The disruption of cholesterol using methyl-beta-cyclodextrin not only
      reduced the binding activity of cytolethal distending toxin subunits on the cell
      membrane but also impaired their delivery and attenuated toxin-induced cell cycle
      arrest. Accordingly, cell intoxication by cytolethal distending toxin was
      restored by cholesterol replenishment. These findings suggest that membrane
      cholesterol plays a critical role in the Campylobacter jejuni cytolethal
      distending toxin-induced pathogenesis of host cells.

PMID- 21730090
TI  - Long-term humoral and cellular immune responses elicited by a heterologous
      Plasmodium vivax apical membrane antigen 1 protein prime/adenovirus boost
      immunization protocol.
AB  - Apical membrane antigen 1 (AMA-1) is an invasion-related Plasmodium antigen that
      is expressed during both intracellular and extracellular asexual stages of the
      parasite's life cycle, making it an ideal target for induction of humoral and
      cellular immune responses that can protect against malaria. We show here that
      when it is administered as a recombinant protein (P) in Montanide ISA720
      adjuvant, followed by a recombinant human type 5 adenovirus (Ad), intense and
      long-lasting Plasmodium vivax AMA-1-specific antibody responses (including both
      IgG1 and IgG2a), as well as proliferative memory T cell responses, can be
      detected in immunized mice. Memory T cells displayed both central (CD44(hi)
      CD62L(hi)) and effector (CD44(hi) CD62L(lo)) phenotypes, with the central memory
      phenotype prevailing (56% of AMA-1-specific proliferating cells). Considering the
      main traits of the memory immune responses induced against AMA-1, this particular
      sequence of immunogens (P followed by Ad), but no others (Ad/Ad, Ad/P, or P/P),
      displayed an optimal synergistic effect. These results give further support to
      the need for preclinical studies of P. vivax vaccine candidate AMA-1 administered
      in prime/boost protocols that include recombinant proteins and adenoviral
      vectors.

PMID- 21730091
TI  - Inactivation of clpB in the pathogen Leptospira interrogans reduces virulence and
      resistance to stress conditions.
AB  - Leptospira interrogans is the causative agent of leptospirosis, which is an
      emerging zoonotic disease. Resistance to stress conditions is largely
      uncharacterized for this bacterium. We therefore decided to analyze a clpB mutant
      that we obtained by random transposon mutagenesis. The mutant did not produce any
      of the two isoforms of ClpB. The clpB mutant exhibited growth defects at 30
      degrees  and 37 degrees C and in poor nutrient medium and showed increased
      susceptibility to oxidative stress, whereas the genetically complemented strain
      was restored in ClpB expression and in vitro wild-type growth. We also showed
      that the clpB mutant was attenuated in virulence in an animal model of acute
      leptospirosis. Our findings demonstrate that ClpB is involved in the general
      stress response. The chaperone is also necessary, either directly or indirectly,
      for the virulence of the pathogen L. interrogans.

PMID- 21730092
TI  - Ventricular septal defect with aortic valve insufficiency in a New Zealand White
      rabbit.
AB  - A heart murmur was detected in a 10 mo old, female New Zealand White rabbit.
      Auscultation revealed cardiac murmurs both at the left and right hemithorax.
      Phonocardiography confirmed the systolic-diastolic nature of the left-sided and
      the systolic character of the right-sided murmur. Electrocardiography showed
      normal sinus rhythm; tall R waves and large T waves in lead II; and deep S waves
      in leads II, III, and aVF. Thoracic radiography demonstrated generalized
      cardiomegaly with prominent pulmonary vasculature. Echocardiography revealed a
      perimembraneous ventricular septal defect with aortic insufficiency. Signs of
      biventricular volume overload, relative pulmonic stenosis, and pulmonary valve
      insufficiency were also seen as consequences of the defect. Necropsy demonstrated
      a ventricular septal defect just below the aortic valve, a dilated pulmonary
      trunk, dilated and hypertrophied ventricles, dilated atria, and rightward
      displacement of the aortic root. Cardiac histopathology showed ventricular
      cardiomyocyte degeneration (swelling and hypereosinophilia of the cytoplasm with
      a loss of cross striation, and nuclear hyperchromasia), cartilaginous metaplasia
      of the aorta, and subendocardial fibrosis of the right ventricular flow tract.

PMID- 21730093
TI  - Endoscopically assisted nasojejunal feeding tube placement: technique and results
      in five dogs.
AB  - Interest in noninvasive feeding tube placement in companion animals led to the
      adaption of a human technique utilizing endoscopy to place nasojejunal feeding
      tubes. Data from medical records in which nasojejunal feeding tubes were
      attempted were reviewed. Feeding tubes were attempted and successfully placed in
      five dogs within a median of 35 min. Feeding tubes remained in place for
      approximately 7 days. Complications included facial irritation (5/5), sneezing
      (5/5), fractured facial sutures (4/5), vomiting (3/5), diarrhea (3/5), crimping
      of feeding tube (3/5), regurgitation (1/5), epistaxis (1/5), clogging of the
      feeding tube (2/5), and oral migration with premature removal of the feeding tube
      (1/5). The deployment technique used in this study was found to be cumbersome.
      Despite minor complications, endoscopy can be used to rapidly and accurately
      place nasoenteric feeding devices.

PMID- 21730094
TI  - Uveodermatologic syndrome in a rat terrier.
AB  - A 4 yr old intact male rat terrier presented with severe bilateral nonresponsive
      panuveitis. Bilateral uveitis, blepharospasm, conjunctival hyperemia, diffuse
      corneal edema, peripheral bullous retinal detachment, and secondary ocular
      hypertension were noted. Ocular lesions progressed despite aggressive medical
      treatment and were followed by cutaneous depigmentation and crusting along the
      nasal planum. Intensive oral and topical anti-inflammatory and topical
      antiglaucoma medications were administered, but the ocular disease progressed. A
      bilateral enucleation was performed. Uveodermatologic syndrome was diagnosed from
      histopathologic examination of a skin biopsy as well as histopathology of both
      globes after bilateral enucleation. To maintain control of the dermatologic
      lesions, oral azathioprine was initiated, but it was not well tolerated by this
      patient. Immunosuppressive doses of oral cyclosporine and anti-inflammatory doses
      of oral prednisone were used to control the depigmentation and crusting skin
      lesions.

PMID- 21730095
TI  - Neuronal ceroid-lipofuscinosis in longhaired Chihuahuas: clinical, pathologic,
      and MRI findings.
AB  - Neuronal ceroid-lipofuscinosis (NCL) is a rare group of inherited
      neurodegenerative lysosomal storage diseases characterized histopathologically by
      the abnormal accumulation of ceroid- or lipofuscin-like lipopigments in neurons
      and other cells throughout the body. The present article describes the clinical,
      pathologic, and magnetic resonance imaging (MRI) findings of the NCL in three
      longhaired Chihuahuas between 16 mo and 24 mo of age. Clinical signs, including
      visual defects and behavioral abnormalities, started between 16 mo and 18 mo of
      age. Cranial MRI findings in all the dogs were characterized by diffuse severe
      dilation of the cerebral sulci, dilated fissures of diencephalons, midbrain, and
      cerebellum, and lateral ventricular enlargement, suggesting atrophy of the
      forebrain. As the most unusual feature, diffuse meningeal thickening was observed
      over the entire cerebrum, which was strongly enhanced on contrast T1-weighted
      images. The dogs' conditions progressed until they each died subsequent to
      continued neurologic deterioration between 23 mo and 24 mo of age.
      Histopathologically, there was severe to moderate neuronal cell loss with diffuse
      astrogliosis throughout the brain. The remaining neuronal cells showed
      intracytoplasmic accumulation of pale to slightly yellow lipopigments mimicking
      ceroid or lipofuscin. The thickened meninges consisted of the proliferation of
      connective tissues with abundant collagen fibers and mild infiltration of
      inflammatory cells suggesting neuroimmune hyperactivity. Although the etiology of
      this neuroimmune hyperactivity is not currently known, MRI findings such as
      meningeal thickening may be a useful diagnostic marker of this variant form of
      canine NCL.

PMID- 21730096
TI  - Transforming NHS ambulance services.

PMID- 21730097
TI  - Short answer question case series: treatment of persistent, refractory seizures.

PMID- 21730098
TI  - Accuracy of the cardiopulmonary resuscitation registry in an emergency
      department.
AB  - BACKGROUND: The cardiopulmonary resuscitation (CPR) registry has been documented
      for medical records and investigational purposes. Although the accuracy of the
      CPR registry is generally adequate, it is difficult to precisely describe CPR in
      emergency situations. OBJECTIVES: To evaluate the accuracy of the CPR registry in
      an emergency department (ED) and to determine whether closed-circuit television
      (CCTV) is useful for recording CPR events. METHODS: To assess the accuracy of the
      CPR registry, CCTV clips of the room in which CPR was performed in the ED and the
      corresponding CPR registry were consecutively collected and reviewed. The
      contents of the registry, specifically the time interval between patient arrival
      and CPR procedures, were compared with those determined by the CCTV clips.
      Accuracy was defined as the frequency of accurately registered time intervals
      differing by <30 s. RESULTS: In a university-based ED between May and November
      2009, 46 CPRs were performed and 150 CPR time intervals were documented in the
      CPR registry. The level of CPR registry accuracy was 54% (81/150). CONCLUSIONS:
      The accuracy of the CPR registry was improved by the use of CCTV. These results
      indicate that more detailed CPR investigations could be performed with the
      addition of CCTV-based information to the CPR registry.

PMID- 21730099
TI  - Tobacco use in Bollywood movies, tobacco promotional activities and their
      association with tobacco use among Indian adolescents.
AB  - BACKGROUND: Smoking in Hollywood movies is a known risk factor for teen smoking
      in the USA and Europe, but little is known about the association between exposure
      to tobacco use in Bollywood movies and teen tobacco use in India. METHODS: A
      cross-sectional sample of 3956 adolescents (eighth and ninth grades, ages 12-16
      years) from 12 randomly selected New Delhi schools was surveyed in 2009,
      assessing tobacco use status, receptivity to tobacco promotions (based on owning
      or being willing to wear tobacco-branded merchandise) and exposure to tobacco use
      in movies. Quartiles of exposure to tobacco use in popular Bollywood movies
      released from 2006 to 2008 (n=59) were determined by content coding them for
      tobacco use and querying the adolescents whether they had seen each one. Logistic
      regression was used to control for covariates including age, gender, parent
      education, school performance, sensation-seeking propensity, family and peer
      tobacco use, and authoritative parenting. RESULTS: Altogether, the 59 movies
      contained 412 tobacco use occurrences. The prevalence of ever tobacco use among
      adolescents was 5.3%. Compared with low-exposure adolescents (quartile 1), the
      adjusted odds of ever tobacco use among high-exposure adolescents (quartile 4)
      was 2.3 (95% CI 1.3 to 3.9). Being receptive to tobacco promotions was also
      associated with higher adjusted odds of ever tobacco use, 2.0 (95% CI 1.4 to
      3.0). CONCLUSION: Watching tobacco use in Bollywood movies and receptivity to
      tobacco promotional activities were both independently associated with ever
      tobacco use among adolescents in India, with ORs being similar to the studies of
      adolescents elsewhere.

PMID- 21730100
TI  - A tobacco-related carcinogen: assessing the impact of smoking behaviours of
      cohabitants on benzene exposure in children.
AB  - BACKGROUND: Secondhand smoke (SHS) represents a major preventable cause of
      morbidity for communities, especially for children, who are more susceptible than
      adults to the adverse effects of passive smoking. SHS contains several
      carcinogens, including benzene. OBJECTIVE: To investigate the role of household
      characteristics and the smoking behaviours of cohabitants in predicting SHS
      derived benzene exposure levels. Methods In this cross-sectional study, 122
      children (aged 5-11 years old) were selected from a school in rural Italy.
      Characteristics of their home environment and the smoking habits of the
      children's cohabitants were obtained via questionnaire, and urinary unmodified
      benzene (u-UB) and cotinine (a specific nicotine metabolite) levels were
      determined from spot urine samples. RESULTS: Significant differences between SHS
      exposed and SHS-unexposed children were found with respect to u-UB levels (median
      values 359.50 and 92.50 ng/litre, respectively; p<0.001). The excretion of u-UB
      increased significantly in parallel to increased SHS exposure as follows:
      unexposed to SHS (median value 92.50 ng/litre)<cohabitant(s) smoker(s) not
      smoking inside the home (282.00 ng/litre)<cohabitant(s) smoking inside the home
      only when children are out (314.50 ng/litre)<cohabitant(s) smoking inside the
      home even when children are in (596.00 ng/litre). The difference between groups
      was significant (p=0.019). CONCLUSIONS: Although smoke-free legislation has
      transformed the smoking behaviours of some, domestic environments remain an
      important source of SHS exposure for children. This fact holds true even in the
      case of parents and other cohabitants who believe they are fully protecting
      children by smoking only outdoors or at home only when the children are not
      present. These findings should be included in Italian community-level health
      promotion interventions for discouraging tobacco use.

PMID- 21730101
TI  - Twitter=quitter? An analysis of Twitter quit smoking social networks.
AB  - OBJECTIVE: Widely popular, Twitter, a free social networking and micro-blogging
      service, offers potential for health promotion. This study examined the activity
      of Twitter quit smoking social network accounts. DESIGN: A cross-sectional
      analysis identified 153 activated Twitter quit smoking accounts dating back to
      2007 and examined recent account activity for the month of August 2010. RESULTS:
      The accounts had a median of 155 followers and 82 total tweets per account; 49%
      of accounts had >100 tweets. Posted content was largely inconsistent with
      clinical guidelines; 48% linked to commercial sites for quitting smoking and 43%
      had tweets on e-cigarettes. In August 2010, 81 of the accounts (53%) were still
      active. CONCLUSIONS: Though popular for building quit smoking social networks,
      many of the Twitter accounts were no longer active, and tweet content was largely
      inconsistent with clinical guidelines. Future research is needed to examine the
      effectiveness of Twitter for supporting smoking cessation.

PMID- 21730102
TI  - Detection bias and the association between inflammatory bowel disease and
      Salmonella and Campylobacter infection.

PMID- 21730103
TI  - Pancreatic ductal adenocarcinoma and acinar cells: a matter of differentiation
      and development?
AB  - Pancreatic ductal adenocarcinoma (PDAC) has long been considered to arise from
      pancreatic ducts on the basis of its morphology, the occurrence of dysplasia in
      putative preneoplastic ductal lesions, and the absence of acinar dysplasia in the
      pancreas of patients with PDAC. However, evidence gathered through both in vitro
      studies and--more importantly--genetic mouse models of PDAC shows that ductal
      type tumours can arise from acinar cells. These findings raise new important
      questions related to PDAC pathophysiology and call for in-depth studies of acinar
      cell differentiation in order to better understand PDAC biology. The authors
      review these issues and discuss how the novel findings should impact on future
      work aiming at early diagnosis and improved outcome of patients with PDAC.

PMID- 21730104
TI  - The natural history of treated PD in an incident, community-based cohort: does
      the future begin?

PMID- 21730105
TI  - The FOXE1 and NKX2-1 loci are associated with susceptibility to papillary thyroid
      carcinoma in the Japanese population.
AB  - BACKGROUND: FOXE1 and NKX2-1 are two known genetic risk factors for the
      predisposition to sporadic papillary thyroid carcinoma (PTC) in Europeans, but
      their association in other ethnicities is still unknown. OBJECTIVE: We aim to
      examine the association of the two genes with Japanese sporadic PTC, which
      exhibits high BRAF(V600E) mutation rate. METHODS: 507 Japanese sporadic PTC cases
      and 2766 controls were genotyped for rs965513 (FOXE1) and rs944289 (NKX2-1). PTC
      cases were also examined for their BRAF(V600E) mutational status. RESULTS: The
      association of both rs965513 (p=1.27*10(-4), OR=1.69, 95% CI 1.29 to 2.21) and
      rs944289 (p=0.0121, OR=1.21, 95% CI 1.04 to 1.39) with the risk of sporadic PTC
      was confirmed. Subgroup analysis based on the BRAF mutational status showed
      strong association of rs965513 with BRAF(V600E)-positive cases (p=2.26*10(-4),
      OR=1.72, 95% CI 1.29 to 2.29), but not with BRAF(V600E)-negative cases (p=0.143,
      OR=1.52, 95% CI 0.87 to 2.65). However, there was no difference in the observed
      effect size between both subgroups. For rs944289, both subgroups showed marginal
      association (p=0.0585, OR=1.17, 95% CI 0.99 to 1.37 for BRAF(V600E)-positive
      cases; p=0.0492, OR=1.35, 95% CI 1.00 to 1.81 for BRAF(V600E)-negative cases).
      CONCLUSIONS: Both FOXE1 and NKX2-1 were associated with the increased risk of
      sporadic Japanese PTC. No clear associations were observed for either SNP with
      BRAF(V600E) status.

PMID- 21730106
TI  - What can exome sequencing do for you?
AB  - Recent advances in next-generation sequencing technologies have brought a
      paradigm shift in how medical researchers investigate both rare and common human
      disorders. The ability cost-effectively to generate genome-wide sequencing data
      with deep coverage in a short time frame is replacing approaches that focus on
      specific regions for gene discovery and clinical testing. While whole genome
      sequencing remains prohibitively expensive for most applications, exome
      sequencing--a technique which focuses on only the protein-coding portion of the
      genome--places many advantages of the emerging technologies into researchers'
      hands. Recent successes using this technology have uncovered genetic defects with
      a limited number of probands regardless of shared genetic heritage, and are
      changing our approach to Mendelian disorders where soon all causative variants,
      genes and their relation to phenotype will be uncovered. The expectation is that,
      in the very near future, this technology will enable us to identify all the
      variants in an individual's personal genome and, in particular, clinically
      relevant alleles. Beyond this, whole genome sequencing is also expected to bring
      a major shift in clinical practice in terms of diagnosis and understanding of
      diseases, ultimately enabling personalised medicine based on one's genome. This
      paper provides an overview of the current and future use of next generation
      sequencing as it relates to whole exome sequencing in human disease by focusing
      on the technical capabilities, limitations and ethical issues associated with
      this technology in the field of genetics and human disease.

PMID- 21730107
TI  - The VPAC2 agonist peptide histidine isoleucine (PHI) up-regulates glutamate
      transport in the corpus callosum of a rat model of amyotrophic lateral sclerosis
      (hSOD1G93A) by inhibiting caspase-3 mediated inactivation of GLT-1a.
AB  - Degeneration of corpus callosum appears in patients with amyotrophic lateral
      sclerosis (ALS) before clinical signs of upper motor neuron death. Considering
      the ALS-associated impairment of astrocytic glutamate uptake, we have
      characterized the expression and activity of the glutamate transporter isoforms
      GLT-1a and GLT-1b in the corpus callosum of transgenic rats expressing a mutated
      form of the human superoxide dismutase 1 (hSOD1(G93A)). We have also studied the
      effect of peptide histidine isoleucine (PHI), a vasoactive intestinal peptide
      (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) receptor 2
      (VPAC(2)) agonist on glutamate transporters both in vivo and in callosal
      astrocytes. Before the onset of motor symptoms, the expression of both
      transporter isoforms was correlated with a constitutive activity of caspase-3.
      This enzyme participates in the down-regulation of GLT-1 in ALS, and here we
      demonstrated its involvement in the selective degradation of GLT-1a in the white
      matter. A single stereotactic injection of PHI into the corpus callosum of
      symptomatic rats decreased caspase-3 activity and promoted GLT-1a expression and
      uptake activity. Together, with evidence for a reduced expression of prepro
      VIP/PHI mRNA in the corpus callosum of transgenic animals, these data shed light
      on the modulatory role of the VIP/PHI system on the glutamatergic transmission in
      ALS.

PMID- 21730109
TI  - The molecular basis of mouse sperm-zona pellucida binding: a still unresolved
      issue in developmental biology.
AB  - During murine fertilization, sperm bind to the specialized extracellular matrix
      of the egg, known as the zona pellucida (ZP). This matrix is composed of three
      major glycoproteins designated ZP1, ZP2, and ZP3. Three models for sperm-ZP
      binding are now under consideration. The domain-specific model posits that
      adhesion relies primarily on interactions between N-glycans located within the C
      terminal domain of ZP3 and a lectin-like egg-binding protein in the sperm plasma
      membrane. However, this model does not explain recent results obtained in studies
      with ZP2(mut) mice. In the supramolecular structure model, sperm bind to a three
      dimensional zona matrix that depends on the cleavage status of ZP2. This paradigm
      does not explain the potent inhibitory effect of specific carbohydrate sequences
      or a C-terminal glycopeptide (gp55) derived from ZP3. Recently, O-glycans linked
      at Thr(155) and Thr(162) of ZP3 were implicated as potential ligands that mediate
      initial sperm-ZP binding. This novel model will be reviewed. A major challenge is
      to develop an alternate model for sperm-ZP binding that fits as much of the data
      as possible. Such a model is presented in this review. This paradigm could
      explain how the inability to cleave ZP2(mut) in ZP2(mut) mice could result in
      continued sperm binding to two-cell stage embryos without the formation of a
      supramolecular binding complex. These novel insights should guide future
      experiments that will eventually determine the molecular basis underlying gamete
      binding in the mouse and other eutherian mammals.

PMID- 21730110
TI  - Altered expression of Armet and Mrlp51 in the oocyte, preimplantation embryo, and
      brain of mice following oocyte in vitro maturation but postnatal brain
      development and cognitive function are normal.
AB  - Despite the efforts to recapitulate the follicle environment, oocytes from in
      vitro maturation (IVM) have poorer developmental potential than those matured in
      vivo and the effects on the resultant offspring are of concern. The aim of this
      study was to determine altered gene expression in oocytes following IVM and to
      evaluate the expression of the arginine rich, mutated in early stage of tumors
      gene (Armet) and mitochondrial ribosomal protein L51 (Mrpl51) in embryos and
      brains of fetal/postnatal mice and the brain development of IVM offspring. An IVM
      mouse model was established while oocytes matured in vivo were used as the
      controls. Suppressive subtractive hybridization (SSH) and RT-PCR/western blot
      were used to analyze the differential expression of genes/proteins between IVM
      and the control group. HE staining and water maze were used to assess the
      histological changes in brain tissue and cognition of the offspring. The rates of
      fertilization, cleavage, and live birth were significantly decreased in IVM
      group. Thirteen genes were upregulated in IVM oocytes compared with the control,
      including Armet and Mrpl51. The higher level of Armet in IVM oocytes was retained
      in brain of newborn mice, which could be related to the upregulation of
      activating transcription factor 6 (Atf6) and X-box binding protein 1 (Xbp1),
      while Mrpl51 was expressed normally in brain of postnatal mice. No significant
      differences were detected in brain weight, neuronal counts, and the cognition in
      the offspring between the two groups. The present results suggested that IVM
      could affect the pregnancy outcome and the Armet and Mrpl51 gene/protein
      expression. The change in Armet expression lasted while the change of Mrpl51
      disappeared after birth. However, the brain development of the offspring seemed
      to be unaffected by IVM.

PMID- 21730111
TI  - Comparison of mRNA for IGFs and their binding proteins in the oviduct during the
      peri-oestrous period between dairy heifers and lactating cows.
AB  - The oviduct provides the environment to support gamete maturation, fertilisation
      and early embryo development. As there is a high incidence of early embryonic
      death in lactating dairy cows, this study compared expression of IGF family
      members in the oviduct between lactating Holstein-Friesian dairy cows (n=16, 81+/
      2.4 days in milk) and nulliparous heifers (n=16, age 1.6+/-0.07 years) at three
      stages of the oestrous cycle: A) newly selected dominant follicle in the luteal
      phase, B) follicular phase before the LH surge and C) pre-ovulatory phase after
      the LH surge. Expression of IGF1, IGF2, IGF binding protein 2 (IGFBP2), IGFBP3
      and IGFBP6 mRNA was determined in the ampulla of the oviduct. Oviduct side
      (ipsilateral or contralateral) with respect to the dominant follicle did not
      affect gene expression. Expression of IGF1 and all three IGFBPs increased
      significantly between the luteal and the pre-ovulatory phases, with no further
      significant alteration post-LH surge. Concentrations of circulating IGF1 were
      higher in heifers than in cows, as was the mRNA expression of IGF1, IGFBP3 and
      IGFBP6. The pre-LH surge rise in IGFBP2 mRNA was only observed in heifers. IGF2
      expression was not influenced by either age or stage of cycle. These three IGFBPs
      are generally considered to inhibit IGF action. These results indicate tight
      regulation of IGF bioavailability in the oviductal environment around oestrus,
      with pronounced differences between cows and heifers, which are likely to
      influence early embryonic development. Further studies are required to assess the
      implications for embryo survival.

PMID- 21730112
TI  - Chemokine response induced by Chlamydia trachomatis in prostate derived CD45+ and
      CD45- cells.
AB  - The role of innate cells and their receptors within the male genital tract
      remains poorly understood. Much less is known about the relative contribution of
      different genital tract cells such as epithelial/stromal cells and resident
      leucocytes. In this study, we examined innate immune responses to Chlamydia
      trachomatis by prostate epithelial/stromal cells and prostate resident
      leucocytes. Murine prostate primary cultures were performed and leucocyte and
      epithelial/stromal cells were sorted based on surface protein expression of CD45
      by magnetism-activated cell sorting or fluorescence-activated cell sorting.
      Prostate derived CD45- and CD45+ cells were infected with C. trachomatis and
      chemokine secretion assayed by ELISA. Similar experiments were performed using
      prostate CD45+ and CD45- cells from myeloid differentiation factor 88 (Myd88(-/
      )) mice or toll-like receptor (Tlr2(-/-)) and Tlr4(mutant) double-deficient mice.
      Moreover, a TLR-signalling pathway array was used to screen changes in different
      genes involved in TLR-signalling pathways by real-time PCR. Prostate derived CD45
      and CD45+ cells responded to chlamydial infection with the production of
      different chemokines. Both populations expressed genes involved in TLR signalling
      and required to respond to pathogen-associated molecular patterns and to C.
      trachomatis infection. Both populations required the adaptor molecule MYD88 to
      elicit chemokine response against C. trachomatis. TLR2-TLR4 was essential for
      chemokine production by CD45+ prostate derived cells, but in their absence, CD45-
      cells still produced significant levels of chemokines. We demonstrate that C.
      trachomatis is differentially recognised by prostate derived CD45+ and CD45-
      cells and suggest that diverse strategies are taking place in the local
      microenvironment of the host in response to the infection.

PMID- 21730113
TI  - Novel genotyping and quantitative analysis of neuraminidase inhibitor resistance
      associated mutations in influenza a viruses by single-nucleotide polymorphism
      analysis.
AB  - Neuraminidase (NA) inhibitors are among the first line of defense against
      influenza virus infection. With the increased worldwide use of the drugs,
      antiviral susceptibility surveillance is increasingly important for effective
      clinical management and for public health epidemiology. Effective monitoring
      requires effective resistance detection methods. We have developed and validated
      a novel genotyping method for rapid detection of established NA inhibitor
      resistance markers in influenza viruses by single nucleotide polymorphism (SNP)
      analysis. The multi- or monoplex SNP analysis based on single nucleotide
      extension assays was developed to detect NA mutations H275Y and I223R/V in
      pandemic H1N1 viruses, H275Y in seasonal H1N1 viruses, E119V and R292K in
      seasonal H3N2 viruses, and H275Y and N295S in H5N1 viruses. The SNP analysis
      demonstrated high sensitivity for low-content NA amplicons (0.1 to 1 ng/MUl) and
      showed 100% accordant results against a panel of defined clinical isolates. The
      monoplex assays for the H275Y NA mutation allowed precise and accurate
      quantification of the proportions of wild-type and mutant genotypes in virus
      mixtures (5% to 10% discrimination), with results comparable to those of
      pyrosequencing. The SNP analysis revealed the lower growth fitness of an H275Y
      mutant compared to the wild-type pandemic H1N1 virus by quantitatively genotyping
      progeny viruses grown in normal human bronchial epithelial cells. This novel
      method offers high-throughput screening capacity, relatively low costs, and the
      wide availability of the necessary equipment, and thus it could provide a much
      needed approach for genotypic screening of NA inhibitor resistance in influenza
      viruses.

PMID- 21730114
TI  - In vivo synergism of ceftobiprole and vancomycin against experimental
      endocarditis due to vancomycin-intermediate Staphylococcus aureus.
AB  - The efficacy of ceftobiprole combined with vancomycin was tested against two
      vancomycin-intermediate Staphylococcus aureus (VISA) strains, PC3 and Mu50, in
      rats with experimental endocarditis. Animals with infected aortic vegetations
      were treated for 3 days with doses simulating the kinetics after intravenous
      administration in humans of (i) the standard dose of ceftobiprole of 500 mg every
      12 h (b.i.d.) (SD-ceftobiprole), (ii) a low dose of ceftobiprole of 250 mg b.i.d.
      (LD-ceftobiprole), (iii) a very low dose of ceftobiprole of 125 mg b.i.d. (VLD
      ceftobiprole), (iv) SD-vancomycin of 1 g b.i.d., or (v) LD- or VLD-ceftobiprole
      combined with SD-vancomycin. Low dosages of ceftobiprole were purposely used to
      highlight positive drug interactions. Treatment with SD-ceftobiprole sterilized
      12 of 14 (86%) and 10 of 13 (77%) vegetations infected with PC3 and Mu50,
      respectively (P < 0.001 versus controls). In comparison, LD-ceftobiprole
      sterilized 10 of 11 (91%) vegetations infected with PC3 (P < 0.01 versus
      controls) but only 3 of 12 (25%) vegetations infected with Mu50 (P > 0.05 versus
      controls). VLD-ceftobiprole and SD-vancomycin alone were ineffective against both
      strains (<=8% sterile vegetations). In contrast, the combination of VLD
      ceftobiprole and SD-vancomycin sterilized 7 of 9 (78%) and 6 of 14 (43%)
      vegetations infected with PC3 and Mu50, respectively, and the combination of LD
      ceftobiprole and SD-vancomycin sterilized 5 of 6 (83%) vegetations infected with
      Mu50 (P < 0.05 versus controls and monotherapy). Thus, ceftobiprole monotherapy
      simulating standard therapeutic doses was active against VISA experimental
      endocarditis. Moreover, subtherapeutic LD- and VLD-ceftobiprole synergized with
      ineffective vancomycin to restore efficacy. Hence, combining ceftobiprole with
      vancomycin broadens the therapeutic margin of these two compounds against VISA
      infections.

PMID- 21730115
TI  - First description of an Escherichia coli strain producing NDM-1 carbapenemase in
      Spain.
AB  - A carbapenem-resistant Escherichia coli strain (DVR22) was recovered from a stool
      specimen from a patient with traveler's diarrhea who had traveled to India.
      Molecular screening led to the first identification of NDM-1 in Spain. The
      bla(NDM-1) gene was located in a conjugative plasmid of ca. 300 kb that also
      contained the bla(CTX-M-15), bla(TEM-1), Deltabla(DHA-1), and armA genes. In
      addition, bla(NDM-1) was preceded by an ISAba125 insertion element only found in
      Acinetobacter spp.

PMID- 21730116
TI  - Ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates
      of Plasmodium falciparum and P. vivax.
AB  - Ferroquine (FQ; SSR97193), a ferrocene-containing 4-aminoquinoline derivate, has
      potent in vitro efficacy against chloroquine (CQ)-resistant Plasmodium falciparum
      and CQ-sensitive P. vivax. In the current study, ex vivo FQ activity was tested
      in multidrug-resistant P. falciparum and P. vivax field isolates using a schizont
      maturation assay. Although FQ showed excellent activity against CQ-sensitive and 
      resistant P. falciparum and P. vivax (median 50% inhibitory concentrations
      [IC(50)s], 9.6 nM and 18.8 nM, respectively), there was significant cross
      susceptibility with the quinoline-based drugs chloroquine, amodiaquine, and
      piperaquine (for P. falciparum, r = 0.546 to 0.700, P < 0.001; for P. vivax, r =
      0.677 to 0.821, P < 0.001). The observed ex vivo cross-susceptibility is likely
      to reflect similar mechanisms of drug uptake/efflux and modes of drug action of
      this drug class. However, the potent activity of FQ against resistant isolates of
      both P. falciparum and P. vivax highlights a promising role for FQ as a lead
      antimalarial against CQ-resistant Plasmodium and a useful partner drug for
      artemisinin-based combination therapy.

PMID- 21730117
TI  - Helicobacter pylori eradication by sitafloxacin-lansoprazole combination and
      sitafloxacin pharmacokinetics in Mongolian gerbils and its in vitro activity and
      resistance development.
AB  - A total of 293 strains of Helicobacter pylori, including strains resistant to
      levofloxacin, clarithromycin, metronidazole, or amoxicillin, were examined for in
      vitro susceptibility to 10 antimicrobial agents. Among these agents, sitafloxacin
      (a fluoroquinolone) showed the greatest activity (MIC(90), 0.06 MUg/ml), with
      high bactericidal activity and synergy in sitafloxacin-lansoprazole (a proton
      pump inhibitor) combination. In a Mongolian gerbil model with a H. pylori ATCC
      43504 challenge, marked eradication effects were observed at >=1 mg/kg for
      sitafloxacin, >=10 mg/kg for levofloxacin, and >=10 mg/kg for lansoprazole,
      reflecting MIC levels for each agent (0.008, 0.25, and 2 MUg/ml, respectively).
      The therapeutic rates were 83.3% for the sitafloxacin (0.3 mg/kg)-lansoprazole
      (2.5 mg/kg) combination and 0% for either sitafloxacin or lansoprazole alone. The
      maximum serum concentration (C(max)) of sitafloxacin was 0.080 +/- 0.054 MUg/ml
      at 30 min, when orally administered at 1 mg/kg. The simultaneous administration
      of lansoprazole resulted in no difference. In the resistance development assay,
      MICs of levofloxacin increased 64- to 256-fold with gyrA mutations (Ala88Pro and
      Asn87Lys), while MICs of sitafloxacin only up to 16-fold with the Asn87Lys
      mutation. The data suggest that sitafloxacin exhibited superior anti-H. pylori
      activity with low rates of resistance development in vitro and that, reflecting
      high in vitro activities, sitafloxacin-lansoprazole combination exhibited strong
      therapeutic effects in Mongolian gerbils with a C(max) of sitafloxacin that was
      10-fold higher than the MIC value at a 1-mg/kg administration.

PMID- 21730118
TI  - Validation of the intact zwittermicin A biosynthetic gene cluster and discovery
      of a complementary resistance mechanism in Bacillus thuringiensis.
AB  - Zwittermicin A (ZmA) is a hybrid polyketide-nonribosomal peptide produced by
      certain Bacillus cereus group strains. It displays broad-spectrum antimicrobial
      activity. Its biosynthetic pathway in B. cereus has been proposed through
      analysis of the nonribosomal peptide synthetase (NRPS) and polyketide synthase
      (PKS) modules involved in ZmA biosynthesis. In this study, we constructed a
      bacterial artificial chromosome (BAC) library from Bacillus thuringiensis subsp.
      kurstaki strain YBT-1520 genomic DNA. The presence of known genes involved in the
      biosynthesis of ZmA in this BAC library was investigated by PCR techniques. Nine
      positive clones were identified, two of which (covering an approximately 60-kb
      region) could confer ZmA biosynthesis ability upon B. thuringiensis BMB171 after
      simultaneous transfer into this host by two compatible shuttle BAC vectors.
      Another previously unidentified gene cluster, named zmaWXY, was found to improve
      the yield of ZmA and was experimentally defined to function as a ZmA resistance
      transporter which expels ZmA from the cells. Putative transposase genes were
      detected on the flanking regions of the two gene clusters (the ZmA synthetic
      cluster and zmaWXY), which suggests a mobile nature of these two gene clusters.
      The intact ZmA gene cluster was validated, and a resistance mechanism
      complementary to that for zmaR (the previously identified ZmA self-resistance
      gene) was revealed. This study also provided a straightforward strategy to
      isolate and identify a huge gene cluster from Bacillus.

PMID- 21730119
TI  - A translation inhibitor that suppresses dengue virus in vitro and in vivo.
AB  - We describe a novel translation inhibitor that has anti-dengue virus (DENV)
      activity in vitro and in vivo. The inhibitor was identified through a high
      throughput screening using a DENV infection assay. The compound contains a
      benzomorphan core structure. Mode-of-action analysis indicated that the compound
      inhibits protein translation in a viral RNA sequence-independent manner. Analysis
      of the stereochemistry demonstrated that only one enantiomer of the racemic
      compound inhibits viral RNA translation. Medicinal chemistry was performed to
      eliminate a metabolically labile glucuronidation site of the compound to improve
      its in vivo stability. Pharmacokinetic analysis showed that upon a single
      subcutaneous dosing of 25 mg/kg of body weight in mice, plasma levels of the
      compound reached a C(max) (maximum plasma drug concentration) above the protein
      binding-adjusted 90% effective concentration (EC(90)) value of 0.96 MUM. In
      agreement with the in vivo pharmacokinetic results, treatment of DENV-infected
      mice with 25 mg/kg of compound once per day reduced peak viremia by about 40
      fold. However, mice treated with 75 mg/kg of compound per day exhibited adverse
      effects. Collectively, our results demonstrate that the benzomorphan compounds
      inhibit DENV through suppression of RNA translation. The therapeutic window of
      the current compounds needs to be improved for further development.

PMID- 21730120
TI  - Pharmacokinetics and ex vivo antimalarial activity of artesunate-azithromycin in
      healthy volunteers.
AB  - In 18 male healthy subjects, artesunate (200 mg)-azithromycin (1,500 mg) daily
      for 3 days was found to be well tolerated, with only mild gastrointestinal
      disturbances reported. The pharmacokinetic properties of artesunate-azithromycin
      given in combination are comparable to those of the drugs given alone. Artesunate
      and its major active metabolite, dihydroartemisinin, are responsible for most of
      the ex vivo antimalarial activity, with a delayed contribution by azithromycin.

PMID- 21730121
TI  - Distant and new mutations in CTX-M-1 beta-lactamase affect cefotaxime hydrolysis.
AB  - The CTX-M beta-lactamases are an increasingly prevalent group of extended
      spectrum beta-lactamases (ESBL). Point mutations in CTX-M beta-lactamases are
      considered critical for enhanced hydrolysis of cefotaxime. In order to clarify
      the structural determinants of the activity against cefotaxime in CTX-M beta
      lactamases, screening for random mutations was carried out to search for
      decreased activity against cefotaxime, with the CTX-M-1 gene as a model. Thirteen
      single mutants with a considerable reduction in cefotaxime MICs were selected for
      biochemical and stability studies. The 13 mutated genes of the CTX-M-1 beta
      lactamase were expressed, and the proteins were purified for kinetic studies
      against cephalothin and cefotaxime (as the main antibiotics). Some of the
      positions, such as Val103Asp, Asn104Asp, Asn106Lys, and Pro107Ser, are located in
      the (103)VNYN(106) loop, which had been described as important in cefotaxime
      hydrolysis, although this has not been experimentally confirmed. There are four
      mutations located close to catalytic residues-Thr71Ile, Met135Ile, Arg164His, and
      Asn244Asp-that may affect the positioning of these residues. We show here that
      some distant mutations, such as Ala219Val, are critical for cefotaxime hydrolysis
      and highlight the role of this loop at the top of the active site. Other distant
      substitutions, such as Val80Ala, Arg191, Ala247Ser, and Val260Leu, are in
      hydrophobic cores and may affect the dynamics and flexibility of the enzyme. We
      describe here, in conclusion, new residues involved in cefotaxime hydrolysis in
      CTX-M beta-lactamases, five of which are in positions distant from the catalytic
      center.

PMID- 21730122
TI  - Phylogenetic sequence variations in bacterial rRNA affect species-specific
      susceptibility to drugs targeting protein synthesis.
AB  - Antibiotics targeting the bacterial ribosome typically bind to highly conserved
      rRNA regions with only minor phylogenetic sequence variations. It is unclear
      whether these sequence variations affect antibiotic susceptibility or resistance
      development. To address this question, we have investigated the drug binding
      pockets of aminoglycosides and macrolides/ketolides. The binding site of
      aminoglycosides is located within helix 44 of the 16S rRNA (A site);
      macrolides/ketolides bind to domain V of the 23S rRNA (peptidyltransferase
      center). We have used mutagenesis of rRNA sequences in Mycobacterium smegmatis
      ribosomes to reconstruct the different bacterial drug binding sites and to study
      the effects of rRNA sequence variations on drug activity. Our results provide a
      rationale for differences in species-specific drug susceptibility patterns and
      species-specific resistance phenotypes associated with mutational alterations in
      the drug binding pocket.

PMID- 21730123
TI  - Antimicrobial activity of B-Lock against bacterial and Candida spp. causing
      catheter-related bloodstream infections.
AB  - The triple combination trimethoprim, EDTA, and ethanol (B-Lock), is an
      antimicrobial lock solution for use in indwelling intravascular catheters to
      prevent and treat catheter-associated infections. B-Lock demonstrated MICs of
      <=0.05% (percentage of solution) against Candida spp. (n = 125) and 0.003% to 25%
      against bacterial strains (n = 175). B-Lock was also fungicidal against the
      majority of the Candida strains at 6% to 25%. B-Lock demonstrates potential value
      for the prevention and treatment of catheter-associated infections.

PMID- 21730124
TI  - Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases.
AB  - Zinc-finger nucleases (ZFNs) are powerful tools for producing gene knockouts
      (KOs) with high efficiency. Whereas ZFN-mediated gene disruption has been
      demonstrated in laboratory animals such as mice, rats, and fruit flies, ZFNs have
      not been used to disrupt an endogenous gene in any large domestic species. Here
      we used ZFNs to induce a biallelic knockout of the porcine alpha1,3
      galactosyltransferase (GGTA1) gene. Primary porcine fibroblasts were treated with
      ZFNs designed against the region coding for the catalytic core of GGTA1,
      resulting in biallelic knockout of ~1% of ZFN-treated cells. A galactose (Gal)
      epitope counter-selected population of these cells was used in somatic cell
      nuclear transfer (SCNT). Of the resulting six fetuses, all completely lacked Gal
      epitopes and were phenotypically indistinguishable from the starting donor cell
      population, illustrating that ZFN-mediated genetic modification did not interfere
      with the cloning process. Neither off-target cleavage events nor integration of
      the ZFN-coding plasmid was detected. The GGTA1-KO phenotype was confirmed by a
      complement lysis assay that demonstrated protection of GGTA1-KO fibroblasts
      relative to wild-type cells. Cells from GGTA1-KO fetuses and pooled, transfected
      cells were used to produce live offspring via SCNT. This study reports the
      production of cloned pigs carrying a biallelic ZFN-induced knockout of an
      endogenous gene. These findings open a unique avenue toward the creation of gene
      KO pigs, which could benefit both agriculture and biomedicine.

PMID- 21730126
TI  - Orphan nuclear transcription factor TR3/Nur77 regulates microvessel permeability
      by targeting endothelial nitric oxide synthase and destabilizing endothelial
      junctions.
AB  - Low-level basal vascular permeability (BVP) provides nutrients to normal tissues,
      and increased vascular permeability is characteristic of inflammation and cancer.
      We recently reported that VEGF-A, a potent vascular permeabilizing and angiogenic
      factor, exerts much of its angiogenic activity by up-regulating expression of
      TR3/Nur77, an orphan nuclear transcription factor, in vascular endothelial cells
      (EC). To determine whether TR3/Nur77 had a more general role in regulating
      vascular permeability, we found that histamine, serotonin, and platelet
      activating factor, small molecule vascular permeabilizing agents, also increased
      TR3/Nur77 expression acutely in EC. BVP and the acute vascular hyperpermeability
      (AVH) induced by these vascular permeabilizing factors were greatly decreased in
      Nur77(-/-) mice, and both BVP and AVH correlated with Nur77 expression levels in
      several different mouse strains. BVP and AVH were enhanced in transgenic mice in
      which Nur77 was selectively overexpressed in vascular EC, whereas both were
      suppressed in mice overexpressing dominant-negative Nur77. Chronic vascular
      hyperpermeability (CVH) was induced long before the onset of angiogenesis in a
      modified, in vivo Matrigel assay that included PT67 cells packaging retroviruses
      expressing Nur77-sense, whereas inclusion of cells packaging viruses expressing
      Nur77-antisense prevented VEGF-A-induced CVH. TR3/Nur77 modulated vascular
      permeability by increasing endothelial nitric-oxide synthase expression and by
      downregulating several EC junction proteins that maintain vascular homeostasis.
      Both functions required TR3/Nur77 transcriptional activity. Taking these data
      together, TR3/Nur77 is up-regulated by several vascular permeabilizing agents and
      has critical roles in mediating BVP, AVH, and CVH.

PMID- 21730127
TI  - Maternal bisphenol A (BPA) decreases attractiveness of male offspring.

PMID- 21730128
TI  - Rerooting the evolutionary tree of malaria parasites.
AB  - Malaria parasites (Plasmodium spp.) have plagued humans for millennia. Less well
      known are related parasites (Haemosporida), with diverse life cycles and dipteran
      vectors that infect other vertebrates. Understanding the evolution of parasite
      life histories, including switches between hosts and vectors, depends on
      knowledge of evolutionary relationships among parasite lineages. In particular,
      inferences concerning time of origin and trait evolution require correct
      placement of the root of the evolutionary tree. Phylogenetic reconstructions of
      the diversification of malaria parasites from DNA sequences have suffered from
      uncertainty concerning outgroup taxa, limited taxon sampling, and selection on
      genes used to assess relationships. As a result, inferred relationships among the
      Haemosporida have been unstable, and questions concerning evolutionary
      diversification and host switching remain unanswered. A recent phylogeny placed
      mammalian malaria parasites, as well as avian/reptilian Plasmodium, in a derived
      position relative to the avian parasite genera Leucocytozoon and Haemoproteus,
      implying that the ancestral forms lacked merogony in the blood and that their
      vectors were non-mosquito dipterans. Bayesian, outgroup-free phylogenetic
      reconstruction using relaxed molecular clocks with uncorrelated rates instead
      suggested that mammalian and avian/reptilian Plasmodium parasites, spread by
      mosquito vectors, are ancestral sister taxa, from which a variety of specialized
      parasite lineages with modified life histories have evolved.

PMID- 21730129
TI  - Critical role for macrophage migration inhibitory factor (MIF) in Ross River
      virus-induced arthritis and myositis.
AB  - Arthrogenic alphaviruses, such as Ross River virus (RRV), chikungunya, Sindbis,
      mayaro and o'nyong-nyong viruses circulate endemically worldwide, frequently
      causing outbreaks of polyarthritis. The exact mechanisms of how alphaviruses
      induce polyarthritis remain ill defined, although macrophages are known to play a
      key role. Macrophage migration inhibitory factor (MIF) is an important cytokine
      involved in rheumatoid arthritis pathogenesis. Here, we characterize the role of
      MIF in alphavirus-induced arthritides using a mouse model of RRV-induced
      arthritis, which has many characteristics of RRV disease in humans. RRV-infected
      WT mice developed severe disease associated with up-regulated MIF expression in
      serum and tissues, which corresponded to severe inflammation and tissue damage.
      MIF-deficient (MIF(-/-)) mice developed mild disease accompanied by a reduction
      in inflammatory infiltrates and muscle destruction in the tissues, despite having
      viral titers similar to WT mice. In addition, reconstitution of MIF into MIF(-/-)
      mice exacerbated RRV disease and treatment of mice with MIF antagonist
      ameliorated disease in WT mice. Collectively, these findings suggest that MIF
      plays a critical role in determining the clinical severity of alphavirus-induced
      musculoskeletal disease and may provide a target for the development of antiviral
      pharmaceuticals. The prospect being that early treatment with MIF-blocking
      pharmaceuticals may curtail the debilitating arthritis associated with alphaviral
      infections.

PMID- 21730125
TI  - Demographic history and rare allele sharing among human populations.
AB  - High-throughput sequencing technology enables population-level surveys of human
      genomic variation. Here, we examine the joint allele frequency distributions
      across continental human populations and present an approach for combining
      complementary aspects of whole-genome, low-coverage data and targeted high
      coverage data. We apply this approach to data generated by the pilot phase of the
      Thousand Genomes Project, including whole-genome 2-4* coverage data for 179
      samples from HapMap European, Asian, and African panels as well as high-coverage
      target sequencing of the exons of 800 genes from 697 individuals in seven
      populations. We use the site frequency spectra obtained from these data to infer
      demographic parameters for an Out-of-Africa model for populations of African,
      European, and Asian descent and to predict, by a jackknife-based approach, the
      amount of genetic diversity that will be discovered as sample sizes are
      increased. We predict that the number of discovered nonsynonymous coding variants
      will reach 100,000 in each population after ~1,000 sequenced chromosomes per
      population, whereas ~2,500 chromosomes will be needed for the same number of
      synonymous variants. Beyond this point, the number of segregating sites in the
      European and Asian panel populations is expected to overcome that of the African
      panel because of faster recent population growth. Overall, we find that the
      majority of human genomic variable sites are rare and exhibit little sharing
      among diverged populations. Our results emphasize that replication of disease
      association for specific rare genetic variants across diverged populations must
      overcome both reduced statistical power because of rarity and higher population
      divergence.

PMID- 21730130
TI  - Functional prokaryotic-eukaryotic chimera from the pentameric ligand-gated ion
      channel family.
AB  - Pentameric ligand-gated ion channels (pLGICs), which mediate chemo-electric
      signal transduction in animals, have been recently found in bacteria. Despite
      clear sequence and 3D structure homology, the phylogenetic distance between
      prokaryotic and eukaryotic homologs suggests significant structural divergences,
      especially at the interface between the extracellular (ECD) and the transmembrane
      (TMD) domains. To challenge this possibility, we constructed a chimera in which
      the ECD of the bacterial protein GLIC is fused to the TMD of the human alpha1
      glycine receptor (alpha1GlyR). Electrophysiology in Xenopus oocytes shows that it
      functions as a proton-gated ion channel, thereby locating the proton activation
      site(s) of GLIC in its ECD. Patch-clamp experiments in BHK cells show that the
      ion channel displays an anionic selectivity with a unitary conductance identical
      to that of the alpha1GlyR. In addition, pharmacological investigations result in
      transmembrane allosteric modulation similar to the one observed on alpha1GlyR.
      Indeed, the clinically active drugs propofol, four volatile general anesthetics,
      alcohols, and ivermectin all potentiate the chimera while they inhibit GLIC.
      Collectively, this work shows the compatibility between GLIC and alpha1GlyR
      domains and points to conservation of the ion channel and transmembrane
      allosteric regulatory sites in the chimera. This provides evidence that GLIC and
      alpha1GlyR share a highly homologous 3D structure. GLIC is thus a relevant model
      of eukaryotic pLGICs, at least from the anionic type. In addition, the chimera is
      a good candidate for mass production in Escherichia coli, opening the way for
      investigations of "druggable" eukaryotic allosteric sites by X-ray
      crystallography.

PMID- 21730131
TI  - E-cadherin mediates contact inhibition of proliferation through Hippo signaling
      pathway components.
AB  - Contact inhibition of cell growth is essential for embryonic development and
      maintenance of tissue architecture in adult organisms, and the growth of tumors
      is characterized by a loss of contact inhibition of proliferation. The recently
      identified Hippo signaling pathway has been implicated in contact inhibition of
      proliferation as well as organ size control. The modulation of the
      phosphorylation and nuclear localization of Yes-associated protein (YAP) by the
      highly conserved kinase cascade of the Hippo signaling pathway has been
      intensively studied. However, cell-surface receptors regulating the Hippo
      signaling pathway in mammals are not well understood. In this study, we show that
      Hippo signaling pathway components are required for E-cadherin-dependent contact
      inhibition of proliferation. Knockdown of the Hippo signaling components or
      overexpression of YAP inhibits the decrease in cell proliferation caused by E
      cadherin homophilic binding at the cell surface, independent of other cell-cell
      interactions. We also demonstrate that the E-cadherin/catenin complex functions
      as an upstream regulator of the Hippo signaling pathway in mammalian cells.
      Expression of E-cadherin in MDA-MB-231 cells restores the density-dependent
      regulation of YAP nuclear exclusion. Knockdown of beta-catenin in densely
      cultured MCF10A cells, which mainly depletes E-cadherin-bound beta-catenin,
      induces a decrease in the phosphorylation of S127 residue of YAP and its nuclear
      accumulation. Moreover, E-cadherin homophilic binding independent of other cell
      interactions is sufficient to control the subcellular localization of YAP.
      Therefore, Our results indicate that, in addition to its role in cell-cell
      adhesion, E-cadherin-mediated cell-cell contact directly regulates the Hippo
      signaling pathway to control cell proliferation.

PMID- 21730132
TI  - Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity
      during embryogenesis but dispensable for p53 and Mdm2 stability.
AB  - Mdm2 and Mdm4 are homologous RING domain-containing proteins that negatively
      regulate the tumor suppressor p53 under physiological and stress conditions. The
      RING domain of Mdm2 encodes an E3-ubiquitin ligase that promotes p53 degradation.
      In addition, Mdm2 and Mdm4 interact through their respective RING domains. The in
      vivo significance of Mdm2-Mdm4 heterodimerization in regulation of p53 function
      is unknown. In this study, we generated an Mdm4 conditional allele lacking the
      RING domain to investigate its role in Mdm2 and p53 regulation. Our results
      demonstrate that homozygous deletion of the Mdm4 RING domain results in prenatal
      lethality. Mechanistically, Mdm2-Mdm4 heterodimerization is critical for
      inhibiting lethal p53 activation during early embryogenesis. However, Mdm2-Mdm4
      interaction is dispensable for regulating p53 activity as well as the stability
      of Mdm2 and p53 at later stages of development. We propose that Mdm4 is a key
      cofactor of Mdm2 that inhibits p53 activity primarily during early embryogenesis
      but is dispensable for regulating p53 and Mdm2 stability in the adult mouse.

PMID- 21730133
TI  - Apoptosis inhibitor of macrophage (AIM) is required for obesity-associated
      recruitment of inflammatory macrophages into adipose tissue.
AB  - Infiltration of inflammatory macrophages into adipose tissues with the
      progression of obesity triggers insulin resistance and obesity-related metabolic
      diseases. We recently reported that macrophage-derived apoptosis inhibitor of
      macrophage (AIM) protein is increased in blood in line with obesity progression
      and is incorporated into adipocytes, thereby inducing lipolysis in adipose
      tissue. Here we show that such a response is required for the recruitment of
      adipose tissue macrophages. In vitro, AIM-dependent lipolysis induced an efflux
      of palmitic and stearic acids from 3T3-L1 adipocytes, thereby stimulating
      chemokine production in adipocytes via activation of toll-like receptor 4 (TLR4).
      In vivo administration of recombinant AIM to TLR4-deficient (TLR4(-/-)) mice
      resulted in induction of lipolysis without chemokine production in adipose
      tissues. Consistently, mRNA levels for the chemokines that affect macrophages
      were far lower in AIM-deficient (AIM(-/-)) than in wild-type (AIM(+/+)) obese
      adipose tissue. This reduction in chemokine production resulted in a marked
      prevention of inflammatory macrophage infiltration into adipose tissue in obese
      AIM(-/-) mice, although these mice showed more advanced obesity than AIM(+/+)
      mice on a high-fat diet. Diminished macrophage infiltration resulted in decreased
      inflammation locally and systemically in obese AIM(-/-) mice, thereby protecting
      them from insulin resistance and glucose intolerance. These results indicate that
      the increase in blood AIM is a critical event for the initiation of macrophage
      recruitment into adipose tissue, which is followed by insulin resistance. Thus,
      AIM suppression might be therapeutically applicable for the prevention of obesity
      related metabolic disorders.

PMID- 21730134
TI  - Cysteine scanning and modification reveal major differences between BK channels
      and Kv channels in the inner pore region.
AB  - BK channels are regulated by two distinct physiological signals, transmembrane
      potential and intracellular Ca(2+), each acting through independent modular
      sensor domains. However, despite a presumably central role in the coupling of
      sensor activation to channel gating, the pore-lining S6 transmembrane segment has
      not been systematically studied. Here, cysteine substitution and modification
      studies of the BK S6 point to substantial differences between BK and Kv channels
      in the structure and function of the S6-lined inner pore. Gating shifts caused by
      introduction of cysteines define a pattern and direction of free energy changes
      in BK S6 distinct from Shaker. Modification of BK S6 residues identifies pore
      facing residues that occur at different linear positions along aligned BK and Kv
      S6 segments. Periodicity analysis suggests that one factor contributing to these
      differences may be a disruption of the BK S6 alpha-helix from the unique
      diglycine motif at the position of the Kv hinge glycine. State-dependent MTS
      accessibility reveals that, even in closed states, modification can occur.
      Furthermore, the inner pore of BK channels is much larger than that of K(+)
      channels with solved crystal structures. The results suggest caution in the use
      of Kv channel structures as templates for BK homology models, at least in the
      pore-gate domain.

PMID- 21730135
TI  - African monkeys are infected by Plasmodium falciparum nonhuman primate-specific
      strains.
AB  - Recent molecular exploration of the Plasmodium species circulating in great apes
      in Africa has revealed the existence of a large and previously unknown diversity
      of Plasmodium. For instance, gorillas were found to be infected by parasites
      closely related to Plasmodium falciparum, suggesting that the human malignant
      malaria agent may have arisen after a transfer from gorillas. Although this
      scenario is likely in light of the data collected in great apes, it remained to
      be ascertained whether P. falciparum-related parasites may infect other nonhuman
      primates in Africa. Using molecular tools, we here explore the diversity of
      Plasmodium species infecting monkeys in Central Africa. In addition to previously
      described Hepatocystis and Plasmodium species (Plasmodium gonderi and Plasmodium
      sp DAJ-2004), we have found one African monkey to be infected by a P. falciparum
      related parasite. Examination of the nuclear and mitochondrial genomes of this
      parasite reveals that it is specific of nonhuman primates, indicating that P.
      falciparum-related pathogens can naturally circulate in some monkey populations
      in Africa. We also show that at least two distinct genetic entities of P.
      falciparum infect nonhuman primates and humans, respectively. Our discoveries
      bring into question the proposed gorilla origin of human P. falciparum.

PMID- 21730136
TI  - Structural equation models and the quantification of behavior.
AB  - Quantifying behavior often involves using variables that contain measurement
      errors and formulating multiequations to capture the relationship among a set of
      variables. Structural equation models (SEMs) refer to modeling techniques popular
      in the social and behavioral sciences that are equipped to handle multiequation
      models, multiple measures of concepts, and measurement error. This work provides
      an overview of latent variable SEMs. We present the equations for SEMs and the
      steps in modeling, and we provide three illustrations of SEMs. We suggest that
      the general nature of the model is capable of handling a variety of problems in
      the quantification of behavior, where the researcher has sufficient knowledge to
      formulate hypotheses.

PMID- 21730137
TI  - The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires
      endosomal sorting complex responsible for transport (ESCRT) function.
AB  - The function of signaling receptors is tightly controlled by their intracellular
      trafficking. One major regulatory mechanism within the endo-lysosomal system
      required for receptor localization and down-regulation is protein modification by
      ubiquitination and downstream interactions with the endosomal sorting complex
      responsible for transport (ESCRT) machinery. Whether and how these mechanisms
      operate to regulate endosomal sorting of mammalian G protein-coupled receptors
      (GPCRs) remains unclear. Here, we explore the involvement of ubiquitin and ESCRTs
      in the trafficking of OA1, a pigment cell-specific GPCR, target of mutations in
      Ocular Albinism type 1, which localizes intracellularly to melanosomes to
      regulate their biogenesis. Using biochemical and morphological methods in
      combination with overexpression and inactivation approaches we show that OA1 is
      ubiquitinated and that its intracellular sorting and down-regulation requires
      functional ESCRT components. Depletion or overexpression of subunits of ESCRT-0, 
      I, and -III markedly inhibits OA1 degradation with concomitant retention within
      the modified endosomal system. Our data further show that OA1 ubiquitination is
      uniquely required for targeting to the intralumenal vesicles of multivesicular
      endosomes, thereby regulating the balance between down-regulation and delivery to
      melanosomes. This study highlights the role of ubiquitination and the ESCRT
      machinery in the intracellular trafficking of mammalian GPCRs and has
      implications for the physiopathology of ocular albinism type 1.

PMID- 21730138
TI  - Childbearing impeded education more than education impeded childbearing among
      Norwegian women.
AB  - In most societies, women at age 39 with higher levels of education have fewer
      children. To understand this association, we investigated the effects of
      childbearing on educational attainment and the effects of education on fertility
      in the 1964 birth cohort of Norwegian women. Using detailed annual data from ages
      17 to 39, we estimated the probabilities of an additional birth, a change in
      educational level, and enrollment in the coming year, conditional on fertility
      history, educational level, and enrollment history at the beginning of each year.
      A simple model reproduced a declining gradient of children ever born with
      increasing educational level at age 39. When a counterfactual simulation assumed
      no effects of childbearing on educational progression or enrollment (without
      changing the estimated effects of education on childbearing), the simulated
      number of children ever born decreased very little with increasing completed
      educational level, contrary to data. However, when another counterfactual
      simulation assumed no effects of current educational level and enrollment on
      childbearing (without changing the estimated effects of childbearing on
      education), the simulated number of children ever born decreased with increasing
      completed educational level nearly as much as the decrease in the data. In
      summary, in these Norwegian data, childbearing impeded education much more than
      education impeded childbearing. These results suggest that women with advanced
      degrees have lower completed fertility on the average principally because women
      who have one or more children early are more likely to leave or not enter long
      educational tracks and never attain a high educational level.

PMID- 21730139
TI  - Interhomolog recombination and loss of heterozygosity in wild-type and Bloom
      syndrome helicase (BLM)-deficient mammalian cells.
AB  - Genomic integrity often is compromised in tumor cells, as illustrated by genetic
      alterations leading to loss of heterozygosity (LOH). One mechanism of LOH is
      mitotic crossover recombination between homologous chromosomes, potentially
      initiated by a double-strand break (DSB). To examine LOH associated with DSB
      induced interhomolog recombination, we analyzed recombination events using a
      reporter in mouse embryonic stem cells derived from F1 hybrid embryos. In this
      study, we were able to identify LOH events although they occur only rarely in
      wild-type cells (<=2.5%). The low frequency of LOH during interhomolog
      recombination suggests that crossing over is rare in wild-type cells. Candidate
      factors that may suppress crossovers include the RecQ helicase deficient in Bloom
      syndrome cells (BLM), which is part of a complex that dissolves recombination
      intermediates. We analyzed interhomolog recombination in BLM-deficient cells and
      found that, although interhomolog recombination is slightly decreased in the
      absence of BLM, LOH is increased by fivefold or more, implying significantly
      increased interhomolog crossing over. These events frequently are associated with
      a second homologous recombination event, which may be related to the mitotic
      bivalent structure and/or the cell-cycle stage at which the initiating DSB
      occurs.

PMID- 21730140
TI  - Ezrin-mediated apical integrity is required for intestinal homeostasis.
AB  - Individual cell types are defined by architecturally and functionally specialized
      cortical domains. The Ezrin, Radixin, and Moesin (ERM) proteins play a major role
      in organizing cortical domains by assembling membrane protein complexes and
      linking them to the cortical actin cytoskeleton. Many studies have focused on the
      individual roles of the ERM proteins in stabilizing the membrane-cytoskeleton
      interface, controlling the distribution and function of apical membrane
      complexes, regulating the small GTPase Rho, or establishing cell-cell junctions.
      We previously found that deletion of the mouse Ezrin gene yields severe defects
      in apical integrity throughout the developing intestinal epithelium, resulting in
      incomplete villus morphogenesis and neonatal death. However, the molecular
      function of Ezrin in building the apical surface of the intestinal epithelium was
      not clear. By deleting Ezrin in the adult mouse intestinal epithelium, we provide
      evidence that Ezrin performs multiple molecular functions that collaborate to
      build the functional apical surface of the intestinal epithelium in vivo. The
      loss of Ezrin-mediated apical integrity in the adult intestine yields severe
      morphological consequences during intestinal homeostasis, including defects in
      cell geometry, extrusion, junctional remodeling, and spindle orientation.
      Surprisingly, deletion of Ezrin either before or after villus morphogenesis
      yields villus fusion, revealing a previously unrecognized step in intestinal
      homeostasis. Our studies indicate that the function of Ezrin in building and
      maintaining the apical domain is essential not only for intestinal morphogenesis
      but also for homeostasis in the mature intestine.

PMID- 21730142
TI  - Molecular determinants for selective recognition of antidepressants in the human
      serotonin and norepinephrine transporters.
AB  - Inhibitors of the serotonin transporter (SERT) and norepinephrine transporter
      (NET) are widely used in the treatment of major depressive disorder. Although
      SERT/NET selectivity is a key determinant for the therapeutic properties of these
      drugs, the molecular determinants defining SERT/NET selectivity are poorly
      understood. In this study, the structural basis for selectivity of the SERT
      selective inhibitor citalopram and the structurally closely related NET selective
      inhibitor talopram is delineated. A systematic structure-activity relationship
      study allowed identification of the substituents that control activity and
      selectivity toward SERT and NET and revealed a common pattern showing that SERT
      and NET have opposite preference for the stereochemical configuration of these
      inhibitors. Mutational analysis of nonconserved SERT/NET residues within the
      central substrate binding site was performed to determine the molecular basis for
      inhibitor selectivity. Changing only five residues in NET to the complementary
      residues in SERT transferred a SERT-like affinity profile for R- and S-citalopram
      into NET, showing that the selectivity of these compounds is determined by amino
      acid differences in the central binding site of the transporters. In contrast,
      the activity of R- and S-talopram was largely unaffected by any mutations within
      the central substrate binding site of SERT and NET and in the outer vestibule of
      NET, suggesting that citalopram and talopram bind to distinct sites on SERT and
      NET. Together, these findings provide important insight into the molecular basis
      for SERT/NET selectivity of antidepressants, which can be used to guide rational
      development of unique transporter inhibitors with fine-tuned transporter
      selectivity.

PMID- 21730141
TI  - DNA methylation regulates phenotype-dependent transcriptional activity in Candida
      albicans.
AB  - DNA methylation is a common epigenetic signaling mechanism associated with
      silencing of repeated DNA and transcriptional regulation in eukaryotes. Here we
      report that DNA methylation in the human fungal pathogen Candida albicans is
      primarily localized within structural genes and modulates transcriptional
      activity. Major repeat sequences and multigene families are largely free of DNA
      methylation. Among the genes subject to DNA methylation are those associated with
      dimorphic transition between yeast and hyphal forms, switching between white and
      opaque cells, and iron metabolism. Transcriptionally repressed methylated loci
      showed increased frequency of C-to-T transitions during asexual growth, an
      evolutionarily stable pattern of repression associated mutation that could bring
      about genetic alterations under changing environmental or host conditions.
      Dynamic differential DNA methylation of structural genes may be one factor
      contributing to morphological plasticity that is cued by nutrition and host
      interaction.

PMID- 21730143
TI  - Dissection of the Burkholderia intracellular life cycle using a photothermal
      nanoblade.
AB  - Burkholderia pseudomallei and Burkholderia thailandensis are related pathogens
      that invade a variety of cell types, replicate in the cytoplasm, and spread to
      nearby cells. We have investigated temporal and spatial requirements for
      virulence determinants in the intracellular life cycle, using genetic dissection
      and photothermal nanoblade delivery, which allows efficient placement of
      bacterium-sized cargo into the cytoplasm of mammalian cells. The conserved Bsa
      type III secretion system (T3SS(Bsa)) is dispensable for invasion, but is
      essential for escape from primary endosomes. By nanoblade delivery of B.
      thailandensis we demonstrate that all subsequent events in intercellular spread
      occur independently of T3SS(Bsa) activity. Although intracellular movement was
      essential for cell-cell spread by B. pseudomallei and B. thailandensis, neither
      BimA-mediated actin polymerization nor the formation of membrane protrusions
      containing bacteria was required for B. thailandensis. Surprisingly, the cryptic
      (fla2) flagellar system encoded on chromosome 2 of B. thailandensis supported
      rapid intracellular motility and efficient cell-cell spread. Plaque formation by
      both pathogens was dependent on the activity of a type VI secretion system (T6SS
      1) that functions downstream from T3SS(Bsa)-mediated endosome escape. A
      remarkable feature of Burkholderia is their ability to induce the formation of
      multinucleate giant cells (MNGCs) in multiple cell types. By infection and
      nanoblade delivery, we observed complete correspondence between mutant phenotypes
      in assays for cell fusion and plaque formation, and time-course studies showed
      that plaque formation represents MNGC death. Our data suggest that the primary
      means for intercellular spread involves cell fusion, as opposed to pseudopod
      engulfment and bacterial escape from double-membrane vacuoles.

PMID- 21730144
TI  - Reductive evolution of proteomes and protein structures.
AB  - The lengths of orthologous protein families in Eukarya are almost double the
      lengths found in Bacteria and Archaea. Here we examine protein structures in 745
      genomes and show that protein length differences between superkingdoms arise as
      much shorter prokaryotic nondomain linker sequences. Eukaryotic, bacterial, and
      archaeal linkers are 250, 86, and 73 aa residues in length, respectively, whereas
      folded domain sequences are 281, 280, and 256 residues, respectively. Cryptic
      domains match linkers (P < 0.0001) with probabilities ranging between 0.022 and
      0.042; accordingly, they do not affect length estimates significantly. Linker
      sequences support intermolecular binding within proteomes and they are probably
      enriched in intrinsically disordered regions as well. Reductively evolved linker
      sequence lengths in growth rate maximized cells should be proportional to
      proteome diversity. By using total in-frame coding capacity of a genome [i.e.,
      coding sequence (CDS)] as a reliable measure of proteome diversity, we find
      linker lengths of prokaryotes clearly evolve in proportion to CDS values, whereas
      those of eukaryotes are more randomly larger than expected. Domain lengths
      scarcely change over the entire range of CDS values. Thus, the protein linkers of
      prokaryotes evolve reductively whereas those of eukaryotes do not.

PMID- 21730145
TI  - Multidisciplinary perspectives on banana (Musa spp.) domestication.
AB  - Original multidisciplinary research hereby clarifies the complex geodomestication
      pathways that generated the vast range of banana cultivars (cvs). Genetic
      analyses identify the wild ancestors of modern-day cvs and elucidate several key
      stages of domestication for different cv groups. Archaeology and linguistics shed
      light on the historical roles of people in the movement and cultivation of
      bananas from New Guinea to West Africa during the Holocene. The historical
      reconstruction of domestication processes is essential for breeding programs
      seeking to diversify and improve banana cvs for the future.

PMID- 21730146
TI  - MicroRNA regulation of the paired-box transcription factor Pax3 confers
      robustness to developmental timing of myogenesis.
AB  - Commitment of progenitors in the dermomyotome to myoblast fate is the first step
      in establishing the body musculature. Pax3 is a crucial transcription factor,
      important for skeletal muscle development and expressed in myogenic progenitors
      in the dermomyotome of developing somites and in migratory muscle progenitors
      that populate the limb buds. Down-regulation of Pax3 is essential to ignite the
      myogenic program, including up-regulation of myogenic regulators, Myf-5 and MyoD.
      MicroRNAs (miRNAs) confer robustness to developmental timing by
      posttranscriptional repression of genetic programs that are related to previous
      developmental stages or to alternative cell fates. Here we demonstrate that the
      muscle-specific miRNAs miR-1 and miR-206 directly target Pax3. Antagomir-mediated
      inhibition of miR-1/miR-206 led to delayed myogenic differentiation in developing
      somites, as shown by transient loss of myogenin expression. This correlated with
      increased Pax3 and was phenocopied using Pax3-specific target protectors. Loss of
      myogenin after antagomir injection was rescued by Pax3 knockdown using a splice
      morpholino, suggesting that miR-1/miR-206 control somite myogenesis primarily
      through interactions with Pax3. Our studies reveal an important role for miR
      1/miR-206 in providing precision to the timing of somite myogenesis. We propose
      that posttranscriptional control of Pax3 downstream of miR-1/miR-206 is required
      to stabilize myoblast commitment and subsequent differentiation. Given that
      mutually exclusive expression of miRNAs and their targets is a prevailing theme
      in development, our findings suggest that miRNA may provide a general mechanism
      for the unequivocal commitment underlying stem cell differentiation.

PMID- 21730147
TI  - Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1
      internal genes for transmission in the ferret model.
AB  - In 2009, a novel H1N1 influenza (pH1N1) virus caused the first influenza pandemic
      in 40 y. The virus was identified as a triple reassortant between avian, swine,
      and human influenza viruses, highlighting the importance of reassortment in the
      generation of viruses with pandemic potential. Previously, we showed that a
      reassortant virus composed of wild-type avian H9N2 surface genes in a seasonal
      human H3N2 backbone could gain efficient respiratory droplet transmission in the
      ferret model. Here we determine the ability of the H9N2 surface genes in the
      context of the internal genes of a pH1N1 virus to efficiently transmit via
      respiratory droplets in ferrets. We generated reassorted viruses carrying the HA
      gene alone or in combination with the NA gene of a prototypical H9N2 virus in the
      background of a pH1N1 virus. Four reassortant viruses were generated, with three
      of them showing efficient respiratory droplet transmission. Differences in
      replication efficiency were observed for these viruses; however, the results
      clearly indicate that H9N2 avian influenza viruses and pH1N1 viruses, both of
      which have occasionally infected pigs, have the potential to reassort and
      generate novel viruses with respiratory transmission potential in mammals.

PMID- 21730148
TI  - D2 receptor overexpression in the striatum leads to a deficit in inhibitory
      transmission and dopamine sensitivity in mouse prefrontal cortex.
AB  - Two distinct defects are thought to be important for the pathophysiology of
      schizophrenia. One is an increase of D2 receptors (D2Rs) in the striatum and
      another is a decrease in the GABAergic function in the prefrontal cortex (PFC).
      Whether these two defects are functionally linked is not known. We previously
      reported that selective overexpression of D2Rs in the striatum of the mouse
      causes behavioral abnormality associated with PFC functions. Using patch-clamp
      recording, we find that overexpression of D2Rs in the striatum affects inhibitory
      transmission in the PFC and dopamine (DA) sensitivity. The overexpression of D2Rs
      in the striatum caused an increase in frequency of spontaneous excitatory
      postsynaptic currents (EPSCs) in layer V pyramidal neurons, whereas their
      neuronal excitability was unaffected. In contrast, both the frequency and
      amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) were
      significantly decreased in these mice, indicating a reduced inhibitory
      transmission. Furthermore, in D2R transgenic mice the dopaminergic modulation of
      evoked IPSCs was shifted, with reduced sensitivity. The change in dopamine
      sensitivity in the PFC of D2R transgenic mice appears specific for D2Rs because
      in D2R transgenic mice the effects of D2 agonist but not D1 agonist, on both
      evoked IPSCs and EPSCs, were reduced. Together, these results indicate that
      overexpression of D2Rs in the striatum leads to a functional deficit in the
      GABAergic system. These results provide a functional link between D2R
      overexpression and GABAergic inhibition in the PFC and suggest that the
      postulated deficit in GABAergic function in schizophrenia could be secondary to
      alterations in the striatal dopamine system.

PMID- 21730149
TI  - Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle
      defects in mice by dietary and genetic strategies.
AB  - Increased meiotic spindle abnormalities and aneuploidy in oocytes of women of
      advanced maternal ages lead to elevated rates of infertility, miscarriage, and
      trisomic conceptions. Despite the significance of the problem, strategies to
      sustain oocyte quality with age have remained elusive. Here we report that adult
      female mice maintained under 40% caloric restriction (CR) did not exhibit aging
      related increases in oocyte aneuploidy, chromosomal misalignment on the metaphase
      plate, meiotic spindle abnormalities, or mitochondrial dysfunction (aggregation,
      impaired ATP production), all of which occurred in oocytes of age-matched ad
      libitum-fed controls. The effects of CR on oocyte quality in aging females were
      reproduced by deletion of the metabolic regulator, peroxisome proliferator
      activated receptor gamma coactivator-1alpha (PGC-1alpha). Thus, CR during
      adulthood or loss of PGC-1alpha function maintains female germline chromosomal
      stability and its proper segregation during meiosis, such that ovulated oocytes
      of aged female mice previously maintained on CR or lacking PGC-1alpha are
      comparable to those of young females during prime reproductive life.

PMID- 21730150
TI  - The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic beta
      cell death.
AB  - Death of pancreatic beta cells is a pathological hallmark of type 1 diabetes
      (T1D). However, the molecular mechanisms of beta cell death and its regulation
      are poorly understood. Here we describe a unique regulatory pathway of beta cell
      death that comprises microRNA-21, its target tumor suppressor PDCD4, and its
      upstream transcriptional activator nuclear factor-kappaB (NF-kappaB). In
      pancreatic beta cells, c-Rel and p65 of the NF-kappaB family activated the mir21
      gene promoter and increased miR-21 RNA levels; miR-21 in turn decreased the level
      of PDCD4, which is able to induce cell death through the Bax family of apoptotic
      proteins. Consequently, PDCD4 deficiency in pancreatic beta cells renders them
      resistant to death, and PDCD4 deficiency in NOD or C57BL/6 mice conferred
      resistance to spontaneous diabetes and diabetes induced by autoimmune T cells or
      the beta cell toxin streptozotocin (STZ). Thus, the NF-kappaB-microRNA-21-PDCD4
      axis plays a crucial role in T1D and represents a unique therapeutic target for
      treating the disease.

PMID- 21730151
TI  - Speciation with gene flow on Lord Howe Island.
AB  - Understanding the processes underlying the origin of species is a fundamental
      goal of biology. It is widely accepted that speciation requires an interruption
      of gene flow between populations: ongoing gene exchange is considered a major
      hindrance to population divergence and, ultimately, to the evolution of new
      species. Where a geographic barrier to reproductive isolation is lacking, a
      biological mechanism for speciation is required to counterbalance the
      homogenizing effect of gene flow. Speciation with initially strong gene flow is
      thought to be extremely rare, and few convincing empirical examples have been
      published. However, using phylogenetic, karyological, and ecological data for the
      flora of a minute oceanic island (Lord Howe Island, LHI), we demonstrate that
      speciation with gene flow may, in fact, be frequent in some instances and could
      account for one in five of the endemic plant species of LHI. We present 11
      potential instances of species divergence with gene flow, including an in situ
      radiation of five species of Coprosma (Rubiaceae, the coffee family). These
      results, together with the speciation of Howea palms on LHI, challenge current
      views on the origin of species diversity.

PMID- 21730152
TI  - Transcriptome transfer provides a model for understanding the phenotype of
      cardiomyocytes.
AB  - We show that the transfer of the adult ventricular myocyte (AVM) transcriptome
      into either a fibroblast or an astrocyte converts the host cell into a
      cardiomyocyte. Transcriptome-effected cardiomyocytes (tCardiomyocytes) display
      morphologies, immunocytochemical properties, and expression profiles of postnatal
      cardiomyocytes. Cell morphology analysis shows that tCardiomyoctes are elongated
      and have a similar length-to-width ratio as AVMs. These global phenotypic changes
      occur in a time-dependent manner and confer electroexcitability to the
      tCardiomyocytes. tCardiomyocyte generation does not require continuous
      overexpression of specific transcription factors; for example, the expression
      level of transcription factor Mef2c is higher in tCardiomyocytes than in
      fibroblasts, but similar in tCardiomyocytes and AVMs. These data highlight the
      dominant role of the gene expression profile in developing and maintaining
      cellular phenotype. The transcriptome-induced phenotype remodeling-generated
      tCardiomyocyte has significant implications for understanding and modulating
      cardiac disease development.

PMID- 21730153
TI  - A regulatory gene induces trichome formation and embryo lethality in tomato.
AB  - Trichomes are universal biological structures originating from the aerial
      epidermis, which serve as an excellent model to study plant differentiation at
      the cell level. Although the pathway regulating trichome formation in the Rosids
      has been well characterized, only very recently a few genes were identified for
      trichome initiation in the Asterids. In this study, we cloned Woolly (Wo),
      essential for trichome formation in tomato. Transgenic experiments revealed that
      the woolly phenotype is caused by the mutation in Wo which encodes a homeodomain
      protein containing a bZIP motif and a START domain. We identified three alleles
      of Wo and found that each allele contains a missense mutation, which respectively
      results in an amino acid substitution at the C terminus. Microarray and
      expression analysis showed that the expression of a B-type cyclin gene, SlCycB2,
      is possibly regulated by Wo, which also participates in trichome formation.
      Suppression of Wo or SlCycB2 expression by RNAi decreased the number of type I
      trichomes, and direct protein-protein interaction was detected between them,
      implying that both proteins may work together in the regulation of this type of
      trichome formation. Cytological observation and Wo transcript analysis in the
      developing seeds showed that embryo development was also correlated with Wo.

PMID- 21730154
TI  - Inequality, communication, and the avoidance of disastrous climate change in a
      public goods game.
AB  - International efforts to provide global public goods often face the challenges of
      coordinating national contributions and distributing costs equitably in the face
      of uncertainty, inequality, and free-riding incentives. In an experimental
      setting, we distribute endowments unequally among a group of people who can reach
      a fixed target sum through successive money contributions, knowing that if they
      fail, they will lose all their remaining money with 50% probability. In some
      treatments, we give players the option to communicate intended contributions. We
      find that inequality reduces the prospects of reaching the target but that
      communication increases success dramatically. Successful groups tend to eliminate
      inequality over the course of the game, with rich players signaling willingness
      to redistribute early on. Our results suggest that coordination-promoting
      institutions and early redistribution from richer to poorer nations are both
      decisive for the avoidance of global calamities, such as disruptive climate
      change.

PMID- 21730155
TI  - Biodiversity hotspots house most undiscovered plant species.
AB  - For most organisms, the number of described species considerably underestimates
      how many exist. This is itself a problem and causes secondary complications given
      present high rates of species extinction. Known numbers of flowering plants form
      the basis of biodiversity "hotspots"--places where high levels of endemism and
      habitat loss coincide to produce high extinction rates. How different would
      conservation priorities be if the catalog were complete? Approximately 15% more
      species of flowering plant are likely still undiscovered. They are almost
      certainly rare, and depending on where they live, suffer high risks of extinction
      from habitat loss and global climate disruption. By using a model that
      incorporates taxonomic effort over time, regions predicted to contain large
      numbers of undiscovered species are already conservation priorities. Our results
      leave global conservation priorities more or less intact, but suggest
      considerably higher levels of species imperilment than previously acknowledged.

PMID- 21730156
TI  - Maintenance of tumor initiating cells of defined genetic composition by
      nucleostemin.
AB  - Recent work has identified a subset of cells resident in tumors that exhibit
      properties similar to those found in normal stem cells. Such cells are highly
      tumorigenic and may be involved in resistance to treatment. However, the genes
      that regulate the tumor initiating cell (TIC) state are unknown. Here, we show
      that overexpression of either of the nucleolar GTP-binding proteins nucleostemin
      (NS) or GNL3L drives the fraction of genetically defined tumor cells that exhibit
      markers and tumorigenic properties of TICs. Specifically, cells that
      constitutively express elevated levels of NS or GNL3L exhibit increased TWIST
      expression, phosphorylation of STAT3, expression of genes that induce pluripotent
      stem cells, and enhanced radioresistance; in addition, they form tumors even when
      small numbers of cells are implanted and exhibit an increased propensity to
      metastasize. GNL3L/NS forms a complex with the telomerase catalytic subunit
      [human telomerase reverse transcriptase (hTERT)] and the SWItch-Sucrose
      NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), and the
      expression of each of these components is necessary to facilitate the cancer stem
      cell state. Together, these observations define a complex composed of TERT, BRG1,
      and NS/GNL3L that maintains the function of TICs.

PMID- 21730157
TI  - Bioluminescence resonance energy transfer (BRET) imaging of protein-protein
      interactions within deep tissues of living subjects.
AB  - Identifying protein-protein interactions (PPIs) is essential for understanding
      various disease mechanisms and developing new therapeutic approaches. Current
      methods for assaying cellular intermolecular interactions are mainly used for
      cells in culture and have limited use for the noninvasive assessment of small
      animal disease models. Here, we describe red light-emitting reporter systems
      based on bioluminescence resonance energy transfer (BRET) that allow for assaying
      PPIs both in cell culture and deep tissues of small animals. These BRET systems
      consist of the recently developed Renilla reniformis luciferase (RLuc) variants
      RLuc8 and RLuc8.6, used as BRET donors, combined with two red fluorescent
      proteins, TagRFP and TurboFP635, as BRET acceptors. In addition to the native
      coelenterazine luciferase substrate, we used the synthetic derivative
      coelenterazine-v, which further red-shifts the emission maxima of Renilla
      luciferases by 35 nm. We show the use of these BRET systems for ratiometric
      imaging of both cells in culture and deep-tissue small animal tumor models and
      validate their applicability for studying PPIs in mice in the context of
      rapamycin-induced FK506 binding protein 12 (FKBP12)-FKBP12 rapamycin binding
      domain (FRB) association. These red light-emitting BRET systems have great
      potential for investigating PPIs in the context of drug screening and target
      validation applications.

PMID- 21730158
TI  - Smad6 promotes neuronal differentiation in the intermediate zone of the dorsal
      neural tube by inhibition of the Wnt/beta-catenin pathway.
AB  - Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular
      zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic
      protein (BMP). However, how these two signaling pathways are regulated to
      initiate differentiation in the NPCs as they enter the intermediate zone is not
      known. Here, we show that Smad6, a negative regulator of BMP signaling, is
      expressed in the intermediate zone of the chick dorsal spinal cord. Knockdown
      experiments show that Smad6 is required for promoting NPCs to exit the cell cycle
      and differentiate into neurons. Although we find that Smad6 inhibits BMP
      signaling, as expected, we also find that Smad6 unexpectedly inhibits the
      Wnt/beta-catenin pathway. The inhibition of the Wnt/beta-catenin pathway by Smad6
      is independent of its effect on the BMP pathway. Rather, Smad6 through its N
      terminal domain and link region enhances the interaction of C-terminal binding
      protein with the beta-catenin/T cell factor (TCF) complex and the TCF-binding
      element to inhibit beta-catenin-mediated transcriptional activation. Our study
      provides evidence that transition of NPCs from a proliferative state to a
      differentiating state is controlled by the dual inhibitory role of Smad6 to both
      BMP and Wnt signaling at the level of transcription.

PMID- 21730159
TI  - Small-molecule inhibitor binding to an N-acyl-homoserine lactone synthase.
AB  - Quorum sensing (QS) controls certain behaviors of bacteria in response to
      population density. In gram-negative bacteria, QS is often mediated by N-acyl-L
      homoserine lactones (acyl-HSLs). Because QS influences the virulence of many
      pathogenic bacteria, synthetic inhibitors of acyl-HSL synthases might be useful
      therapeutically for controlling pathogens. However, rational design of a potent
      QS antagonist has been thwarted by the lack of information concerning the binding
      interactions between acyl-HSL synthases and their ligands. In the gram-negative
      bacterium Burkholderia glumae, QS controls virulence, motility, and protein
      secretion and is mediated by the binding of N-octanoyl-L-HSL (C8-HSL) to its
      cognate receptor, TofR. C8-HSL is synthesized by the acyl-HSL synthase TofI. In
      this study, we characterized two previously unknown QS inhibitors identified in a
      focused library of acyl-HSL analogs. Our functional and X-ray crystal structure
      analyses show that the first inhibitor, J8-C8, binds to TofI, occupying the
      binding site for the acyl chain of the TofI cognate substrate, acylated acyl
      carrier protein. Moreover, the reaction byproduct, 5'-methylthioadenosine,
      independently binds to the binding site for a second substrate, S-adenosyl-L
      methionine. Closer inspection of the mode of J8-C8 binding to TofI provides a
      likely molecular basis for the various substrate specificities of acyl-HSL
      synthases. The second inhibitor, E9C-3oxoC6, competitively inhibits C8-HSL
      binding to TofR. Our analysis of the binding of an inhibitor and a reaction
      byproduct to an acyl-HSL synthase may facilitate the design of a new class of QS
      inhibiting therapeutic agents.

PMID- 21730160
TI  - CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and
      memory in a mouse model of Gaucher-related synucleinopathy.
AB  - Emerging genetic and clinical evidence suggests a link between Gaucher disease
      and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here,
      we provide evidence that a mouse model of Gaucher disease (Gba1(D409V/D409V))
      exhibits characteristics of synucleinopathies, including progressive accumulation
      of proteinase K-resistant alpha-synuclein/ubiquitin aggregates in hippocampal
      neurons and a coincident memory deficit. Analysis of homozygous
      (Gba1(D409V/D409V)) and heterozygous (Gba1(D409V/+) and Gba1(+/-)) Gaucher mice
      indicated that these pathologies are a result of the combination of a loss of
      glucocerebrosidase activity and a toxic gain-of-function resulting from
      expression of the mutant enzyme. Importantly, adeno-associated virus-mediated
      expression of exogenous glucocerebrosidase injected into the hippocampus of
      Gba1(D409V/D409V) mice ameliorated both the histopathological and memory
      aberrations. The data support the contention that mutations in GBA1 can cause
      Parkinson disease-like alpha-synuclein pathology, and that rescuing brain
      glucocerebrosidase activity might represent a therapeutic strategy for GBA1
      associated synucleinopathies.

PMID- 21730161
TI  - Endocannabinoid signal in the gut controls dietary fat intake.
AB  - Oral sensory signals drive dietary fat intake, but the neural mechanisms
      underlying this process are largely unknown. The endocannabinoid system has
      gained recent attention for its central and peripheral roles in regulating food
      intake, energy balance, and reward. Here, we used a sham-feeding paradigm, which
      isolates orosensory from postingestive influences of foods, to examine whether
      endocannabinoid signaling participates in the positive feedback control of fat
      intake. Sham feeding a lipid-based meal stimulated endocannabinoid mobilization
      in the rat proximal small intestine by altering enzymatic activities that control
      endocannabinoid metabolism. This effect was abolished by surgical transection of
      the vagus nerve and was not observed in other peripheral organs or in brain
      regions that control feeding. Sham feeding of a nutritionally complete liquid
      meal produced a similar response to that of fat, whereas protein or carbohydrate
      alone had no such effect. Local infusion of the CB(1)-cannabinoid receptor
      antagonist, rimonabant, into the duodenum markedly reduced fat sham feeding.
      Similarly to rimonabant, systemic administration of the peripherally restricted
      CB(1)-receptor antagonist, URB 447, attenuated sham feeding of lipid.
      Collectively, the results suggest that the endocannabinoid system in the gut
      exerts a powerful regulatory control over fat intake and might be a target for
      antiobesity drugs.

PMID- 21730162
TI  - Structural basis for alcohol modulation of a pentameric ligand-gated ion channel.
AB  - Despite its long history of use and abuse in human culture, the molecular basis
      for alcohol action in the brain is poorly understood. The recent determination of
      the atomic-scale structure of GLIC, a prokaryotic member of the pentameric ligand
      gated ion channel (pLGIC) family, provides a unique opportunity to characterize
      the structural basis for modulation of these channels, many of which are alcohol
      targets in brain. We observed that GLIC recapitulates bimodal modulation by n
      alcohols, similar to some eukaryotic pLGICs: methanol and ethanol weakly
      potentiated proton-activated currents in GLIC, whereas n-alcohols larger than
      ethanol inhibited them. Mapping of residues important to alcohol modulation of
      ionotropic receptors for glycine, gamma-aminobutyric acid, and acetylcholine onto
      GLIC revealed their proximity to transmembrane cavities that may accommodate one
      or more alcohol molecules. Site-directed mutations in the pore-lining M2 helix
      allowed the identification of four residues that influence alcohol potentiation,
      with the direction of their effects reflecting alpha-helical structure. At one of
      the potentiation-enhancing residues, decreased side chain volume converted GLIC
      into a highly ethanol-sensitive channel, comparable to its eukaryotic relatives.
      Covalent labeling of M2 positions with an alcohol analog, a methanethiosulfonate
      reagent, further implicated residues at the extracellular end of the helix in
      alcohol binding. Molecular dynamics simulations elucidated the structural
      consequences of a potentiation-enhancing mutation and suggested a structural
      mechanism for alcohol potentiation via interaction with a transmembrane cavity
      previously termed the "linking tunnel." These results provide a unique structural
      model for independent potentiating and inhibitory interactions of n-alcohols with
      a pLGIC family member.

PMID- 21730163
TI  - The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in
      vivo.
AB  - There are currently two distinct models proposed to explain why both MDM2 and
      MDMX are required in p53 control, with a key difference centered on whether these
      two p53 inhibitors work together or independently. To test these two competing
      models, we generated knockin mice expressing a point mutation MDMX mutant (C462A)
      that is defective in MDM2 binding. This approach allowed a targeted
      disassociation of the MDM2/MDMX heterocomplex without affecting the ability of
      MDMX to bind to p53, and while leaving the MDM2 protein itself completely
      untouched. Significantly, Mdmx(C462A/C462A) homozygous mice died at approximately
      day 9.5 of embryonic development, as the result of a combination of apoptosis and
      decreased cell proliferation, as shown by TUNEL and BrdU incorporation assays,
      respectively. Interestingly, even though the MDMX mutant protein abundance was
      found slightly elevated in the Mdmx(C462A/C462A) homozygous embryos, both the
      abundance and activity of p53 were markedly increased. A p53-dependent death was
      demonstrated by the finding that concomitant deletion of p53 completely rescued
      the embryonic lethality in Mdmx(C462A/C462A) homozygous mice. Our data
      demonstrate that MDM2 and MDMX function as an integral complex in p53 control,
      providing insights into the nonredundant nature of the function of MDM2 and MDMX.

PMID- 21730164
TI  - Order by disorder in the antiferromagnetic Ising model on an elastic triangular
      lattice.
AB  - Geometrically frustrated materials have a ground-state degeneracy that may be
      lifted by subtle effects, such as higher-order interactions causing small
      energetic preferences for ordered structures. Alternatively, ordering may result
      from entropic differences between configurations in an effect termed order by
      disorder. Motivated by recent experiments in a frustrated colloidal system in
      which ordering is suspected to result from entropy, we consider in this paper the
      antiferromagnetic Ising model on a deformable triangular lattice. We calculate
      the displacements exactly at the microscopic level and, contrary to previous
      studies, find a partially disordered ground state of randomly zigzagging stripes.
      Each such configuration is deformed differently and thus has a unique phonon
      spectrum with distinct entropy, lifting the degeneracy at finite temperature.
      Nonetheless, due to the free-energy barriers between the ground-state
      configurations, the system falls into a disordered glassy state.

PMID- 21730165
TI  - Observing Majorana bound states of Josephson vortices in topological
      superconductors.
AB  - In recent years there has been an intensive search for Majorana fermion states in
      condensed matter systems. Predicted to be localized on cores of vortices in
      certain nonconventional superconductors, their presence is known to render the
      exchange statistics of bulk vortices non-abelian. Here we study the equations
      governing the dynamics of phase solitons (fluxons) in a Josephson junction in a
      topological superconductor. We show that the fluxon will bind a localized zero
      energy Majorana mode and will consequently behave as a non-abelian anyon. The low
      mass of the fluxon, as well as its experimentally observed quantum mechanical
      wave-like nature, will make it a suitable candidate for vortex interferometry
      experiments demonstrating non-abelian statistics. We suggest two experiments that
      may reveal the presence of the zero mode carried by the fluxon. Specific
      experimental realizations will be discussed as well.

PMID- 21730166
TI  - Multiscale simulations suggest a mechanism for integrin inside-out activation.
AB  - Integrins are large cell-surface adhesion receptors that can be activated to a
      high affinity state by the formation of an intracellular complex between the
      integrin beta-subunit tail, the membrane, and talin. The F2 and F3 subdomains of
      the talin head play a key role in formation of this complex. Here, activation of
      the integrin alphaIIb/beta3 dimer by the talin head domain was probed using
      multiscale molecular dynamics simulations. A number of novel insights emerge from
      these studies, including (i) the importance of the integrin alphaIIb subunit F992
      and F993 residues in stabilizing the "off" state of the alphaIIb/beta3 dimer,
      (ii) a crucial role for negatively charged groups in the F2-F3/membrane
      interaction, (iii) binding of the talin F2-F3 domain to negatively charged lipid
      headgroups in the membrane induces a reorientation of the beta transmembrane (TM)
      domain, (iv) an increase in the tilt angle of the beta TM domain relative to the
      bilayer normal helps to destabilize the alpha/beta TM interaction and promote a
      scissor-like movement of the integrin TM helices. These results, combined with
      various published experimental observations, suggest a model for the mechanism of
      inside-out activation of integrins by talin.

PMID- 21730167
TI  - From the Cover: Simplifying the representation of complex free-energy landscapes
      using sketch-map.
AB  - A new scheme, sketch-map, for obtaining a low-dimensional representation of the
      region of phase space explored during an enhanced dynamics simulation is
      proposed. We show evidence, from an examination of the distribution of pairwise
      distances between frames, that some features of the free-energy surface are
      inherently high-dimensional. This makes dimensionality reduction problematic
      because the data does not satisfy the assumptions made in conventional manifold
      learning algorithms We therefore propose that when dimensionality reduction is
      performed on trajectory data one should think of the resultant embedding as a
      quickly sketched set of directions rather than a road map. In other words, the
      embedding tells one about the connectivity between states but does not provide
      the vectors that correspond to the slow degrees of freedom. This realization
      informs the development of sketch-map, which endeavors to reproduce the proximity
      information from the high-dimensionality description in a space of lower
      dimensionality even when a faithful embedding is not possible.

PMID- 21730168
TI  - Structure and function of the interacting domains of Spire and Fmn-family
      formins.
AB  - Evidence for cooperation between actin nucleators is growing. The WH2-containing
      nucleator Spire and the formin Cappuccino interact directly, and both are
      essential for assembly of an actin mesh during Drosophila oogenesis. Their
      interaction requires the kinase noncatalytic C-lobe domain (KIND) domain of Spire
      and the C-terminal tail of the formin. Here we describe the crystal structure of
      the KIND domain of human Spir1 alone and in complex with the tail of Fmn2, a
      mammalian ortholog of Cappuccino. The KIND domain is structurally similar to the
      C-lobe of protein kinases. The Fmn2 tail is coordinated in an acidic cleft at the
      base of the domain that appears to have evolved via deletion of a helix from the
      canonical kinase fold. Our functional analysis of Cappuccino reveals an
      unexpected requirement for its tail in actin assembly. In addition, we find that
      the KIND/tail interaction blocks nucleation by Cappuccino and promotes its
      displacement from filament barbed ends providing insight into possible modes of
      cooperation between Spire and Cappuccino.

PMID- 21730169
TI  - Single-molecule investigations of the stringent response machinery in living
      bacterial cells.
AB  - The RelA-mediated stringent response is at the heart of bacterial adaptation to
      starvation and stress, playing a major role in the bacterial cell cycle and
      virulence. RelA integrates several environmental cues and synthesizes the
      alarmone ppGpp, which globally reprograms transcription, translation, and
      replication. We have developed and implemented novel single-molecule tracking
      methodology to characterize the intracellular catalytic cycle of RelA. Our single
      molecule experiments show that RelA is on the ribosome under nonstarved
      conditions and that the individual enzyme molecule stays off the ribosome for an
      extended period of time after activation. This suggests that the catalytically
      active part of the RelA cycle is performed off, rather than on, the ribosome, and
      that rebinding to the ribosome is not necessary to trigger each ppGpp synthesis
      event. Furthermore, we find fast activation of RelA in response to heat stress
      followed by RelA rapidly being reset to its inactive state, which makes the
      system sensitive to new environmental cues and hints at an underlying excitable
      response mechanism.

PMID- 21730170
TI  - Crystal structures of lambda exonuclease in complex with DNA suggest an
      electrostatic ratchet mechanism for processivity.
AB  - The lambda exonuclease is an ATP-independent enzyme that binds to dsDNA ends and
      processively digests the 5'-ended strand to form 5' mononucleotides and a long 3'
      overhang. The crystal structure of lambda exonuclease revealed a toroidal
      homotrimer with a central funnel-shaped channel for tracking along the DNA, and a
      mechanism for processivity based on topological linkage of the trimer to the DNA
      was proposed. Here, we have determined the crystal structure of lambda
      exonuclease in complex with DNA at 1.88-A resolution. The structure reveals that
      the enzyme unwinds the DNA prior to cleavage, such that two nucleotides of the 5'
      ended strand insert into the active site of one subunit of the trimer, while the
      3'-ended strand passes through the central channel to emerge out the back of the
      trimer. Unwinding of the DNA is facilitated by several apolar residues, including
      Leu78, that wedge into the base pairs at the single/double-strand junction to
      form favorable hydrophobic interactions. The terminal 5' phosphate of the DNA
      binds to a positively charged pocket buried at the end of the active site, while
      the scissile phosphate bridges two active site Mg(2+) ions. Our data suggest a
      mechanism for processivity in which wedging of Leu78 and other apolar residues
      into the base pairs of the DNA restricts backward movement, whereas attraction of
      the 5' phosphate to the positively charged pocket drives forward movement of the
      enzyme along the DNA at each cycle of the reaction. Thus, processivity of lambda
      exonuclease operates not only at the level of the trimer, but also at the level
      of the monomer.

PMID- 21730171
TI  - Predicting stochastic systems by noise sampling, and application to the El Nino
      Southern Oscillation.
AB  - Interannual and interdecadal prediction are major challenges of climate dynamics.
      In this article we develop a prediction method for climate processes that exhibit
      low-frequency variability (LFV). The method constructs a nonlinear stochastic
      model from past observations and estimates a path of the "weather" noise that
      drives this model over previous finite-time windows. The method has two steps:
      (i) select noise samples--or "snippets"--from the past noise, which have forced
      the system during short-time intervals that resemble the LFV phase just preceding
      the currently observed state; and (ii) use these snippets to drive the system
      from the current state into the future. The method is placed in the framework of
      pathwise linear-response theory and is then applied to an El Nino-Southern
      Oscillation (ENSO) model derived by the empirical model reduction (EMR)
      methodology; this nonlinear model has 40 coupled, slow, and fast variables. The
      domain of validity of this forecasting procedure depends on the nature of the
      system's pathwise response; it is shown numerically that the ENSO model's
      response is linear on interannual time scales. As a result, the method's skill at
      a 6- to 16-month lead is highly competitive when compared with currently used
      dynamic and statistic prediction methods for the Nino-3 index and the global sea
      surface temperature field.

PMID- 21730172
TI  - Separating intrinsic from extrinsic fluctuations in dynamic biological systems.
AB  - From molecules in cells to organisms in ecosystems, biological populations
      fluctuate due to the intrinsic randomness of individual events and the extrinsic
      influence of changing environments. The combined effect is often too complex for
      effective analysis, and many studies therefore make simplifying assumptions, for
      example ignoring either intrinsic or extrinsic effects to reduce the number of
      model assumptions. Here we mathematically demonstrate how two identical and
      independent reporters embedded in a shared fluctuating environment can be used to
      identify intrinsic and extrinsic noise terms, but also how these contributions
      are qualitatively and quantitatively different from what has been previously
      reported. Furthermore, we show for which classes of biological systems the noise
      contributions identified by dual-reporter methods correspond to the noise
      contributions predicted by correct stochastic models of either intrinsic or
      extrinsic mechanisms. We find that for broad classes of systems, the extrinsic
      noise from the dual-reporter method can be rigorously analyzed using models that
      ignore intrinsic stochasticity. In contrast, the intrinsic noise can be
      rigorously analyzed using models that ignore extrinsic stochasticity only under
      very special conditions that rarely hold in biology. Testing whether the
      conditions are met is rarely possible and the dual-reporter method may thus
      produce flawed conclusions about the properties of the system, particularly about
      the intrinsic noise. Our results contribute toward establishing a rigorous
      framework to analyze dynamically fluctuating biological systems.

PMID- 21730173
TI  - Moire bands in twisted double-layer graphene.
AB  - A moire pattern is formed when two copies of a periodic pattern are overlaid with
      a relative twist. We address the electronic structure of a twisted two-layer
      graphene system, showing that in its continuum Dirac model the moire pattern
      periodicity leads to moire Bloch bands. The two layers become more strongly
      coupled and the Dirac velocity crosses zero several times as the twist angle is
      reduced. For a discrete set of magic angles the velocity vanishes, the lowest
      moire band flattens, and the Dirac-point density-of-states and the counterflow
      conductivity are strongly enhanced.

PMID- 21730174
TI  - Rational growth of branched nanowire heterostructures with synthetically encoded
      properties and function.
AB  - Branched nanostructures represent unique, 3D building blocks for the "bottom-up"
      paradigm of nanoscale science and technology. Here, we report a rational,
      multistep approach toward the general synthesis of 3D branched nanowire (NW)
      heterostructures. Single-crystalline semiconductor, including groups IV, III-V,
      and II-VI, and metal branches have been selectively grown on core or core/shell
      NW backbones, with the composition, morphology, and doping of core (core/shell)
      NWs and branch NWs well controlled during synthesis. Measurements made on the
      different composition branched NW structures demonstrate encoding of functional p
      type/n-type diodes and light-emitting diodes (LEDs) as well as field effect
      transistors with device function localized at the branch/backbone NW junctions.
      In addition, multibranch/backbone NW structures were synthesized and used to
      demonstrate capability to create addressable nanoscale LED arrays, logic
      circuits, and biological sensors. Our work demonstrates a previously undescribed
      level of structural and functional complexity in NW materials, and more
      generally, highlights the potential of bottom-up synthesis to yield increasingly
      complex functional systems in the future.

PMID- 21730175
TI  - Structural and functional analysis of PTPMT1, a phosphatase required for
      cardiolipin synthesis.
AB  - PTPMT1 (PTP localized to the Mitochondrion 1) is a member of the protein tyrosine
      phosphatase superfamily that is localized exclusively to the mitochondrion. We
      recently reported that PTPMT1 dephosphorylates phosphatidylglycerol phosphate, an
      essential intermediate of cardiolipin biosynthesis. To gain further insights into
      the molecular basis of PTPMT1 function, we determined the crystal structures of
      the phosphatase domain of PTPMT1. PTPMT1 exhibits a canonical protein tyrosine
      phosphatase domain fold, resembling many dual-specificity phosphatases such as
      phosphatase and tensin homolog and vaccinia H1-related phosphatase. We also
      determined the structure of the catalytically inactive phosphatase in complex
      with a surrogate substrate, phosphatidylinositol 5-phosphate, which sheds light
      on the substrate recognition and specificity of PTPMT1. Comparison of the apo and
      substrate-bound structures of PTPMT1 suggests that it undergoes significant
      conformational change during catalysis, and we further demonstrated that an
      evolutionarily conserved EEYE loop is important for its activity.

PMID- 21730176
TI  - Protein self-diffusion in crowded solutions.
AB  - Macromolecular crowding in biological media is an essential factor for cellular
      function. The interplay of intermolecular interactions at multiple time and
      length scales governs a fine-tuned system of reaction and transport processes,
      including particularly protein diffusion as a limiting or driving factor. Using
      quasielastic neutron backscattering, we probe the protein self-diffusion in
      crowded aqueous solutions of bovine serum albumin on nanosecond time and
      nanometer length scales employing the same protein as crowding agent. The
      measured diffusion coefficient D(phi) strongly decreases with increasing protein
      volume fraction phi explored within 7% <= phi <= 30%. With an ellipsoidal protein
      model and an analytical framework involving colloid diffusion theory, we separate
      the rotational D(r)(phi) and translational D(t)(phi) contributions to D(phi). The
      resulting D(t)(phi) is described by short-time self-diffusion of effective
      spheres. Protein self-diffusion at biological volume fractions is found to be
      slowed down to 20% of the dilute limit solely due to hydrodynamic interactions.

PMID- 21730177
TI  - Numerical simulations of the Macondo well blowout reveal strong control of oil
      flow by reservoir permeability and exsolution of gas.
AB  - In response to the urgent need for estimates of the oil and gas flow rate from
      the Macondo well MC252-1 blowout, we assembled a small team and carried out oil
      and gas flow simulations using the TOUGH2 codes over two weeks in mid-2010. The
      conceptual model included the oil reservoir and the well with a top boundary
      condition located at the bottom of the blowout preventer. We developed a fluid
      properties module (Eoil) applicable to a simple two-phase and two-component oil
      gas system. The flow of oil and gas was simulated using T2Well, a coupled
      reservoir-wellbore flow model, along with iTOUGH2 for sensitivity analysis and
      uncertainty quantification. The most likely oil flow rate estimated from
      simulations based on the data available in early June 2010 was about 100,000
      bbl/d (barrels per day) with a corresponding gas flow rate of 300 MMscf/d
      (million standard cubic feet per day) assuming the well was open to the reservoir
      over 30 m of thickness. A Monte Carlo analysis of reservoir and fluid properties
      provided an uncertainty distribution with a long tail extending down to 60,000
      bbl/d of oil (170 MMscf/d of gas). The flow rate was most strongly sensitive to
      reservoir permeability. Conceptual model uncertainty was also significant,
      particularly with regard to the length of the well that was open to the
      reservoir. For fluid-entry interval length of 1.5 m, the oil flow rate was about
      56,000 bbl/d. Sensitivity analyses showed that flow rate was not very sensitive
      to pressure-drop across the blowout preventer due to the interplay between gas
      exsolution and oil flow rate.

PMID- 21730178
TI  - Predicting human blood viscosity in silico.
AB  - The viscosity of blood has long been used as an indicator in the understanding
      and treatment of disease, and the advent of modern viscometers allows its
      measurement with ever-improving clinical convenience. However, these advances
      have not been matched by theoretical developments that can yield a quantitative
      understanding of blood's microrheology and its possible connection to relevant
      biomolecules (e.g., fibrinogen). Using coarse-grained molecular dynamics and two
      different red blood cell models, we accurately predict the dependence of blood
      viscosity on shear rate and hematocrit. We explicitly represent cell-cell
      interactions and identify the types and sizes of reversible rouleaux structures
      that yield a tremendous increase of blood viscosity at low shear rates. We also
      present the first quantitative estimates of the magnitude of adhesive forces
      between red cells. In addition, our simulations support the hypothesis,
      previously deduced from experiments, of yield stress as an indicator of cell
      aggregation. This non-Newtonian behavior is analyzed and related to the
      suspension's microstructure, deformation, and dynamics of single red blood cells.
      The most complex cell dynamics occurs in the intermediate shear rate regime,
      where individual cells experience severe deformation and transient folded
      conformations. The generality of these cell models together with single-cell
      measurements points to the future prediction of blood-viscosity anomalies and the
      corresponding microstructures associated with various diseases (e.g., malaria,
      AIDS, and diabetes mellitus). The models can easily be adapted to tune the
      properties of a much wider class of complex fluids including capsule and vesicle
      suspensions.

PMID- 21730179
TI  - Targeting the regulation of androgen receptor signaling by the heat shock protein
      90 cochaperone FKBP52 in prostate cancer cells.
AB  - Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR
      regulatory mechanisms are promising alternatives for the treatment of castrate
      resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an
      important positive regulator of AR in cellular and whole animal models and
      represents an attractive target for the treatment of prostate cancer. We used a
      modified receptor-mediated reporter assay in yeast to screen a diversified
      natural compound library for inhibitors of FKBP52-enhanced AR function. The lead
      compound, termed MJC13, inhibits AR function by preventing hormone-dependent
      dissociation of the Hsp90-FKBP52-AR complex, which results in less hormone-bound
      receptor in the nucleus. Assays in early and late stage human prostate cancer
      cells demonstrated that MJC13 inhibits AR-dependent gene expression and androgen
      stimulated prostate cancer cell proliferation.

PMID- 21730180
TI  - Reconciling anthropogenic climate change with observed temperature 1998-2008.
AB  - Given the widely noted increase in the warming effects of rising greenhouse gas
      concentrations, it has been unclear why global surface temperatures did not rise
      between 1998 and 2008. We find that this hiatus in warming coincides with a
      period of little increase in the sum of anthropogenic and natural forcings.
      Declining solar insolation as part of a normal eleven-year cycle, and a cyclical
      change from an El Nino to a La Nina dominate our measure of anthropogenic effects
      because rapid growth in short-lived sulfur emissions partially offsets rising
      greenhouse gas concentrations. As such, we find that recent global temperature
      records are consistent with the existing understanding of the relationship among
      global surface temperature, internal variability, and radiative forcing, which
      includes anthropogenic factors with well known warming and cooling effects.

PMID- 21730181
TI  - Architecture of the high mobility group nucleosomal protein 2-nucleosome complex
      as revealed by methyl-based NMR.
AB  - Chromatin structure and function are regulated by numerous proteins through
      specific binding to nucleosomes. The structural basis of many of these
      interactions is unknown, as in the case of the high mobility group nucleosomal
      (HMGN) protein family that regulates various chromatin functions, including
      transcription. Here, we report the architecture of the HMGN2-nucleosome complex
      determined by a combination of methyl-transverse relaxation optimized nuclear
      magnetic resonance spectroscopy (methyl-TROSY) and mutational analysis. We found
      that HMGN2 binds to both the acidic patch in the H2A-H2B dimer and to nucleosomal
      DNA near the entry/exit point, "stapling" the histone core and the DNA. These
      results provide insight into how HMGNs regulate chromatin structure through
      interfering with the binding of linker histone H1 to the nucleosome as well as a
      structural basis of how phosphorylation induces dissociation of HMGNs from
      chromatin during mitosis. Importantly, our approach is generally applicable to
      the study of nucleosome-binding interactions in chromatin.

PMID- 21730182
TI  - In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and
      reverses RNA toxicity in myotonic dystrophy models.
AB  - Myotonic dystrophy type 1 (DM1) is caused by the expansion of noncoding CTG
      repeats in the dystrophia myotonica-protein kinase gene. Mutant transcripts form
      CUG hairpins that sequester RNA-binding factors into nuclear foci, including
      Muscleblind-like-1 protein (MBNL1), which regulate alternative splicing and gene
      expression. To identify molecules that target toxic CUG transcripts in vivo, we
      performed a positional scanning combinatorial peptide library screen using a
      Drosophila model of DM1. The screen identified a D-amino acid hexapeptide (ABP1)
      that reduced CUG foci formation and suppressed CUG-induced lethality and muscle
      degeneration when administered orally. Transgenic expression of natural, L-amino
      acid ABP1 analogues reduced CUG-induced toxicity in fly eyes and muscles.
      Furthermore, ABP1 reversed muscle histopathology and splicing misregulation of
      MBNL1 targets in DM1 model mice. In vitro, ABP1 bound to CUG hairpins and induced
      a switch to a single-stranded conformation. Our findings demonstrate that ABP1
      shows antimyotonic dystrophy activity by targeting the core of CUG toxicity.

PMID- 21730183
TI  - Direct observation of ultrafast-electron-transfer reactions unravels high
      effectiveness of reductive DNA damage.
AB  - Both water and electron-transfer reactions play important roles in chemistry,
      physics, biology, and the environment. Oxidative DNA damage is a well-known
      mechanism, whereas the relative role of reductive DNA damage is unknown. The
      prehydrated electron (e(pre)-), a novel species of electrons in water, is a
      fascinating species due to its fundamental importance in chemistry, biology, and
      the environment. e(pre)- is an ideal agent to observe reductive DNA damage. Here,
      we report both the first in situ femtosecond time-resolved laser spectroscopy
      measurements of ultrafast-electron-transfer (UET) reactions of e(pre)- with
      various scavengers (KNO(3), isopropanol, and dimethyl sulfoxide) and the first
      gel electrophoresis measurements of DNA strand breaks induced by e(pre)- and
      OH(*) radicals co-produced by two-UV-photon photolysis of water. We strikingly
      found that the yield of reductive DNA strand breaks induced by each e(pre)- is
      twice the yield of oxidative DNA strand breaks induced by each OH(*) radical. Our
      results not only unravel the long-standing mystery about the relative role of
      radicals in inducing DNA damage under ionizing radiation, but also challenge the
      conventional notion that oxidative damage is the main pathway for DNA damage. The
      results also show the potential of femtomedicine as a new transdisciplinary
      frontier and the broad significance of UET reactions of e(pre)- in many processes
      in chemistry, physics, biology, and the environment.

PMID- 21730184
TI  - Enhanced production of low energy electrons by alpha particle impact.
AB  - Radiation damage to living tissue stems not only from primary ionizing particles
      but to a substantial fraction from the dissociative attachment of secondary
      electrons with energies below the ionization threshold. We show that the emission
      yield of those low energy electrons increases dramatically in ion-atom collisions
      depending on whether or not the target atoms are isolated or embedded in an
      environment. Only when the atom that has been ionized and excited by the primary
      particle impact is in immediate proximity of another atom is a fragmentation
      route known as interatomic Coulombic decay (ICD) enabled. This leads to the
      emission of a low energy electron. Over the past decade ICD was explored in
      several experiments following photoionization. Most recent results show its
      observation even in water clusters. Here we show the quantitative role of ICD for
      the production of low energy electrons by ion impact, thus approaching a scenario
      closer to that of radiation damage by alpha particles: We choose ion energies on
      the maximum of the Bragg peak where energy is most efficiently deposited in
      tissue. We compare the electron production after colliding He(+) ions on isolated
      Ne atoms and on Ne dimers (Ne(2)). In the latter case the Ne atom impacted is
      surrounded by a most simple environment already opening ICD as a deexcitation
      channel. As a consequence, we find a dramatically enhanced low energy electron
      yield. The results suggest that ICD may have a significant influence on cell
      survival after exposure to ionizing radiation.

PMID- 21730185
TI  - Hydrodynamic property of the cytoplasm is sufficient to mediate cytoplasmic
      streaming in the Caenorhabditis elegans embryo.
AB  - Cytoplasmic streaming is a type of intracellular transport widely seen in nature.
      Cytoplasmic streaming in Caenorhabditis elegans at the one-cell stage is
      bidirectional; the flow near the cortex ("cortical flow") is oriented toward the
      anterior, whereas the flow in the central region ("cytoplasmic flow") is oriented
      toward the posterior. Both cortical flow and cytoplasmic flow depend on non
      muscle-myosin II (NMY-2), which primarily localizes in the cortex. The manner in
      which NMY-2 proteins drive cytoplasmic flow in the opposite direction from remote
      locations has not been fully understood. In this study, we demonstrated that the
      hydrodynamic properties of the cytoplasm are sufficient to mediate the forces
      generated by the cortical myosin to drive bidirectional streaming throughout the
      cytoplasm. We quantified the flow velocities of cytoplasmic streaming using
      particle image velocimetry (PIV) and conducted a three-dimensional hydrodynamic
      simulation using the moving particle semiimplicit method. Our simulation
      quantitatively reconstructed the quantified flow velocity distribution resolved
      through PIV analysis. Furthermore, our PIV analyses detected microtubule
      dependent flows during the pronuclear migration stage. These flows were
      reproduced via hydrodynamic interactions between moving pronuclei and the
      cytoplasm. The agreement of flow dynamics in vivo and in simulation indicates
      that the hydrodynamic properties of the cytoplasm are sufficient to mediate
      cytoplasmic streaming in C. elegans embryos.

PMID- 21730186
TI  - Mechanism of activation gating in the full-length KcsA K+ channel.
AB  - Using a constitutively active channel mutant, we solved the structure of full
      length KcsA in the open conformation at 3.9 A. The structure reveals that the
      activation gate expands about 20 A, exerting a strain on the bulge helices in the
      C-terminal domain and generating side windows large enough to accommodate
      hydrated K(+) ions. Functional and spectroscopic analysis of the gating
      transition provides direct insight into the allosteric coupling between the
      activation gate and the selectivity filter. We show that the movement of the
      inner gate helix is transmitted to the C-terminus as a straightforward expansion,
      leading to an upward movement and the insertion of the top third of the bulge
      helix into the membrane. We suggest that by limiting the extent to which the
      inner gate can open, the cytoplasmic domain also modulates the level of
      inactivation occurring at the selectivity filter.

PMID- 21730187
TI  - A key mechanism underlying sensory experience-dependent maturation of neocortical
      GABAergic circuits in vivo.
AB  - Mechanisms underlying experience-dependent refinement of cortical connections,
      especially GABAergic inhibitory circuits, are unknown. By using a line of mutant
      mice that lack activity-dependent BDNF expression (bdnf-KIV), we show that
      experience regulation of cortical GABAergic network is mediated by activity
      driven BDNF expression. Levels of endogenous BDNF protein in the barrel cortex
      are strongly regulated by sensory inputs from whiskers. There is a severe
      alteration of excitation and inhibition balance in the barrel cortex of bdnf-KIV
      mice as a result of reduced inhibitory but not excitatory conductance. Within the
      inhibitory circuits, the mutant barrel cortex exhibits significantly reduced
      levels of GABA release only from the parvalbumin-expressing fast-spiking (FS)
      interneurons, but not other interneuron subtypes. Postnatal deprivation of
      sensory inputs markedly decreased perisomatic inhibition selectively from FS
      cells in wild-type but not bdnf-KIV mice. These results suggest that postnatal
      experience, through activity-driven BDNF expression, controls cortical
      development by regulating FS cell-mediated perisomatic inhibition in vivo.

PMID- 21730188
TI  - Rapid growth of a hepatocellular carcinoma and the driving mutations revealed by
      cell-population genetic analysis of whole-genome data.
AB  - We present the analysis of the evolution of tumors in a case of hepatocellular
      carcinoma. This case is particularly informative about cancer growth dynamics and
      the underlying driving mutations. We sampled nine different sections from three
      tumors and seven more sections from the adjacent nontumor tissues. Selected
      sections were subjected to exon as well as whole-genome sequencing. Putative
      somatic mutations were then individually validated across all 9 tumor and 7
      nontumor sections. Among the mutations validated, 24 were amino acid changes; in
      addition, 22 large indels/copy number variants (>1 Mb) were detected. These
      somatic mutations define four evolutionary lineages among tumor cells. Separate
      evolution and expansion of these lineages were recent and rapid, each apparently
      having only one lineage-specific protein-coding mutation. Hence, by using a cell
      population genetic definition, this approach identified three coding changes
      (CCNG1, P62, and an indel/fusion gene) as tumor driver mutations. These three
      mutations, affecting cell cycle control and apoptosis, are functionally distinct
      from mutations that accumulated earlier, many of which are involved in
      inflammation/immunity or cell anchoring. These distinct functions of mutations at
      different stages may reflect the genetic interactions underlying tumor growth.

PMID- 21730189
TI  - T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing
      epigenome modifications.
AB  - The heterochromatin barrier must be overcome to generate induced pluripotent stem
      cells and cell fusion-mediated reprogrammed hybrids. Here, we show that the
      absence of T-cell factor 3 (Tcf3), a repressor of beta-catenin target genes,
      strikingly and rapidly enhances the efficiency of neural precursor cell (NPC)
      reprogramming. Remarkably, Tcf3(-/-) ES cells showed a genome-wide increase in
      AcH3 and decrease in H3K9me3 and can reprogram NPCs after fusion greatly. In
      addition, during reprogramming of NPCs into induced pluripotent stem cells, the
      silencing of Tcf3 increased AcH3 and decreased the number of H3K9me3-positive
      heterochromatin foci early and long before reactivation of the endogenous stem
      cell genes. In conclusion, our data suggest that Tcf3 functions as a repressor of
      the reprogramming potential of somatic cells.

PMID- 21730190
TI  - Advancing a clinically relevant perspective of the clonal nature of cancer.
AB  - Cancers frequently arise as a result of an acquired genomic instability and the
      subsequent clonal evolution of neoplastic cells with variable patterns of genetic
      aberrations. Thus, the presence and behaviors of distinct clonal populations in
      each patient's tumor may underlie multiple clinical phenotypes in cancers. We
      applied DNA content-based flow sorting to identify and isolate the nuclei of
      clonal populations from tumor biopsies, which was coupled with array CGH and
      targeted resequencing. The results produced high-definition genomic profiles of
      clonal populations from 40 pancreatic adenocarcinomas and a set of prostate
      adenocarcinomas, including serial biopsies from a patient who progressed to
      androgen-independent metastatic disease. The genomes of clonal populations were
      found to have patient-specific aberrations of clinical relevance. Furthermore, we
      identified genomic aberrations specific to therapeutically responsive and
      resistant clones arising during the evolution of androgen-independent metastatic
      prostate adenocarcinoma. We also distinguished divergent clonal populations
      within single biopsies and mapped aberrations in multiple aneuploid populations
      arising in primary and metastatic pancreatic adenocarcinoma. We propose that our
      high-definition analyses of the genomes of distinct clonal populations of cancer
      cells in patients in vivo can help guide diagnoses and tailor approaches to
      personalized treatment.

PMID- 21730191
TI  - DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic
      chromosome segregation.
AB  - During mitosis, faithful inheritance of genetic material is achieved by
      chromosome segregation, as mediated by the condensin I and II complexes. Failed
      chromosome segregation can result in neoplasm formation, infertility, and birth
      defects. Recently, the germ-line-specific DEAD-box RNA helicase Vasa was
      demonstrated to promote mitotic chromosome segregation in Drosophila by
      facilitating robust chromosomal localization of Barren (Barr), a condensin I
      component. This mitotic function of Vasa is mediated by Aubergine and Spindle-E,
      which are two germ-line components of the Piwi-interacting RNA pathway. Faithful
      segregation of chromosomes should be executed both in germ-line and somatic
      cells. However, whether a similar mechanism also functions in promoting
      chromosome segregation in somatic cells has not been elucidated. Here, we present
      evidence that belle (vasa paralog) and the RNA interference pathway regulate
      chromosome segregation in Drosophila somatic cells. During mitosis, belle
      promotes robust Barr chromosomal localization and chromosome segregation. Belle's
      localization to condensing chromosomes depends on dicer-2 and argonaute2.
      Coimmunoprecipitation experiments indicated that Belle interacts with Barr and
      Argonaute2 and is enriched at endogenous siRNA (endo-siRNA)-generating loci. Our
      results suggest that Belle functions in promoting chromosome segregation in
      Drosophila somatic cells via the endo-siRNA pathway. DDX3 (human homolog of
      belle) and DICER function in promoting chromosome segregation and hCAP-H (human
      homolog of Barr) localization in HeLa cells, indicating a conserved function for
      those proteins in human cells. Our results suggest that the RNA helicase
      Belle/DDX3 and the RNA interference pathway perform a common role in regulating
      chromosome segregation in Drosophila and human somatic cells.

PMID- 21730192
TI  - A neural basis for real-world visual search in human occipitotemporal cortex.
AB  - Mammals are highly skilled in rapidly detecting objects in cluttered natural
      environments, a skill necessary for survival. What are the neural mechanisms
      mediating detection of objects in natural scenes? Here, we use human brain
      imaging to address the role of top-down preparatory processes in the detection of
      familiar object categories in real-world environments. Brain activity was
      measured while participants were preparing to detect highly variable depictions
      of people or cars in natural scenes that were new to the participants. The
      preparation to detect objects of the target category, in the absence of visual
      input, evoked activity patterns in visual cortex that resembled the response to
      actual exemplars of the target category. Importantly, the selectivity of
      multivoxel preparatory activity patterns in object-selective cortex (OSC)
      predicted target detection performance. By contrast, preparatory activity in
      early visual cortex (V1) was negatively related to search performance. Additional
      behavioral results suggested that the dissociation between OSC and V1 reflected
      the use of different search strategies, linking OSC preparatory activity to
      relatively abstract search preparation and V1 to more specific imagery-like
      preparation. Finally, whole-brain searchlight analyses revealed that, in addition
      to OSC, response patterns in medial prefrontal cortex distinguished the target
      categories based on the search cues alone, suggesting that this region may
      constitute a top-down source of preparatory activity observed in visual cortex.
      These results indicate that in naturalistic situations, when the precise visual
      characteristics of target objects are not known in advance, preparatory activity
      at higher levels of the visual hierarchy selectively mediates visual search.

PMID- 21730193
TI  - Evolution of the V, D, and J gene segments used in the primate gammadelta T-cell
      receptor reveals a dichotomy of conservation and diversity.
AB  - gammadelta T cells are an immunological enigma in that both their function in the
      immune response and the molecular mechanisms behind their activation remain
      unclear. These cells predominate in the epithelia and can be rapidly activated to
      provide an array of responses. However, no homologous gammadelta T-cell
      populations have been identified between humans and mice, and our understanding
      of what these cells recognize as ligands is limited. Here we take an alternative
      approach to understanding human gammadelta T-cell ligand recognition by studying
      the evolutionary forces that have shaped the V, D, and J gene segments that are
      used during somatic rearrangement to generate the gammadelta T-cell receptor. We
      find that distinctly different forces have shaped the gamma and delta loci. The
      Vdelta and Jdelta genes are highly conserved, some even through to mouse. In
      contrast, the gamma-locus is split: the Vgamma9, Vgamma10, and Vgamma11 genes
      represent the conserved region of the Vgamma gene locus whereas the remaining
      Vgamma genes have been evolving rapidly, such that orthology throughout the
      primate lineage is unclear. We have also analyzed the coding versus silent
      substitutions between species within the V and J gene segments and find a
      preference for coding substitutions in the complementarity determining region
      loops of many of the V gene segments. Our results provide a different perspective
      on investigating human gammadelta T-cell recognition, demonstrating that
      diversification at particular gammadelta gene loci has been favored during
      primate evolution, suggesting adaptation of particular V domains to a changing
      ligand environment.

PMID- 21730194
TI  - Quantitative dissection of the simple repression input-output function.
AB  - We present a quantitative case study of transcriptional regulation in which we
      carry out a systematic dialogue between theory and measurement for an important
      and ubiquitous regulatory motif in bacteria, namely, that of simple repression.
      This architecture is realized by a single repressor binding site overlapping the
      promoter. From the theory point of view, this motif is described by a single gene
      regulation function based upon only a few parameters that are convenient
      theoretically and accessible experimentally. The usual approach is turned on its
      side by using the mathematical description of these regulatory motifs as a
      predictive tool to determine the number of repressors in a collection of strains
      with a large variation in repressor copy number. The predictions and
      corresponding measurements are carried out over a large dynamic range in both
      expression fold change (spanning nearly four orders of magnitude) and repressor
      copy number (spanning about two orders of magnitude). The predictions are tested
      by measuring the resulting level of gene expression and are then validated by
      using quantitative immunoblots. The key outcomes of this study include a
      systematic quantitative analysis of the limits and validity of the input-output
      relation for simple repression, a precise determination of the in vivo binding
      energies for DNA-repressor interactions for several distinct repressor binding
      sites, and a repressor census for Lac repressor in Escherichia coli.

PMID- 21730195
TI  - A multidisciplinary approach to promoting healthy subsistence fish consumption in
      culturally distinct communities.
AB  - Methyl mercury is a potent neurotoxin that causes developmental delays in young
      and unborn children and has been linked to neurological and cardiovascular
      degeneration in adults. Methyl mercury is the basis of a state-sponsored fish
      advisory to limit consumption of local fish in North Carolina. This study
      employed methods and analytic constructs from the behavioral and social sciences
      to assess the determinants of subsistence fishing and to promote informed fish
      consumption among culturally distinct and lower income subsistence fishers in
      southeastern North Carolina. Formative research revealed that Native American and
      African American were more likely than Latino residents to know of the fish
      advisory, and to practice procurement and preparation strategies that are
      mistakenly believed to render locally caught fish safe for consumption. Fish
      advisories were developed for each community to promote informed fish consumption
      intentions among residents who consume local fish. The interventions were
      successful in increasing knowledge and healthy intentions among most residents.
      Adherence to some safe fish consumption practices were constrained by cultural
      and economic factors. These results demonstrate the utility of multidisciplinary
      approaches for assessing and reducing human exposure to methyl mercury through
      subsistence fish consumption.

PMID- 21730196
TI  - The role of community-based organizations in adolescent sexual health promotion.
AB  - Many scholars and practitioners have advocated for a more ecological approach to
      sexual health promotion for adolescents, such as one that includes involvement
      from schools, parents, and community organizations. Although extensive research
      has been conducted with schools and parents, little is known about the roles
      community-based organizations (CBOs) may play in the education and promotion of
      sexual health to young people. This study aimed to (a) identify the types of
      sexual health and sexuality-related questions asked by youth and
      programming/services, resources, and referrals currently being provided by CBOs;
      (b) explore the approaches used by CBOs when developing and implementing sexual
      health promotion programs; and (c) compare these findings with those from a
      similar study on school teachers, counselors, and nurses within the same state.
      Data collected from 169 people working in CBOs indicate that a wide variety of
      topics were covered by CBOs through programming and services, resources, and/or
      referral protocols. Topics covered varied in frequency. Overall, participants
      indicated a relatively comprehensive and accessible approach to providing
      sexuality information to youth. The results of this study suggest that CBOs
      should be included in the range of sources to be used for comprehensive sexual
      health promotion. If such organizations are supported with information, training,
      and resources, they could play a valuable role in the promotion of sexual health
      for adolescents.

PMID- 21730197
TI  - Experimental evidence of phosphoenolpyruvate resynthesis from pyruvate in
      illuminated leaves.
AB  - Day respiration is the cornerstone of nitrogen assimilation since it provides
      carbon skeletons to primary metabolism for glutamate (Glu) and glutamine
      synthesis. However, recent studies have suggested that the tricarboxylic acid
      pathway is rate limiting and mitochondrial pyruvate dehydrogenation is partly
      inhibited in the light. Pyruvate may serve as a carbon source for amino acid
      (e.g. alanine) or fatty acid synthesis, but pyruvate metabolism is not well
      documented, and neither is the possible resynthesis of phosphoenolpyruvate (PEP).
      Here, we examined the capacity of pyruvate to convert back to PEP using (13)C and
      (2)H labeling in illuminated cocklebur (Xanthium strumarium) leaves. We show that
      the intramolecular labeling pattern in Glu, 2-oxoglutarate, and malate after
      (13)C-3-pyruvate feeding was consistent with (13)C redistribution from PEP via
      the PEP-carboxylase reaction. Furthermore, the deuterium loss in Glu after
      (2)H(3)-(13)C-3-pyruvate feeding suggests that conversion to PEP and back to
      pyruvate washed out (2)H atoms to the solvent. Our results demonstrate that in
      cocklebur leaves, PEP resynthesis occurred as a flux from pyruvate, approximately
      0.50/00 of the net CO(2) assimilation rate. This is likely to involve pyruvate
      inorganic phosphate dikinase and the fundamental importance of this flux for PEP
      and inorganic phosphate homeostasis is discussed.

PMID- 21730198
TI  - Small heat shock protein Hsp17.8 functions as an AKR2A cofactor in the targeting
      of chloroplast outer membrane proteins in Arabidopsis.
AB  - Plastid proteins that are encoded by the nuclear genome and synthesized in the
      cytosol undergo posttranslational targeting to plastids. Ankyrin repeat protein
      2A (AKR2A) and AKR2B were recently shown to be involved in the targeting of
      proteins to the plastid outer envelope. However, it remains unknown whether other
      factors are involved in this process. In this study, we investigated a factor
      involved in AKR2A-mediated protein targeting to chloroplasts in Arabidopsis
      (Arabidopsis thaliana). Hsp17.8, a member of the class I (CI) cytosolic small
      heat shock proteins (sHsps), was identified in interactions with AKR2A. The
      interaction between Hsp17.8 and AKR2A was further confirmed by
      coimmunoprecipitation experiments. The carboxyl-terminal ankyrin repeat domain of
      AKR2A was responsible for AKR2A binding to Hsp17.8. Other CI cytosolic sHsps also
      interact with AKR2A to varying degrees. Additionally, Hsp17.8 binds to
      chloroplasts in vitro and enhances AKR2A binding to chloroplasts. HSP17.8 was
      expressed under normal growth conditions, and its expression increased after heat
      shock. Hsp17.8 exists as a dimer under normal physiological conditions, and it is
      converted to high oligomeric complexes, ranging from 240 kD to greater than 480
      kD, after heat shock. High levels of Hsp17.8 together with AKR2A resulted in
      increased plastid targeting of Outer Envelope Protein7 (OEP7), a plastid outer
      envelope protein expressed as a green fluorescent protein fusion protein. In
      contrast, artificial microRNA suppression of HSP17.8 and closely related CI
      cytosolic sHSPs in protoplasts resulted in a reduction of OEP7:green fluorescent
      protein targeting to plastids. Based on these data, we propose that Hsp17.8
      functions as an AKR2A cofactor in targeting membrane proteins to plastid outer
      membranes under normal physiological conditions.

PMID- 21730199
TI  - Benzoxazinoid metabolites regulate innate immunity against aphids and fungi in
      maize.
AB  - Benzoxazinoids (BXs), such as 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one
      (DIMBOA), are secondary metabolites in grasses. The first step in BX biosynthesis
      converts indole-3-glycerol phosphate into indole. In maize (Zea mays), this
      reaction is catalyzed by either BENZOXAZINELESS1 (BX1) or INDOLE GLYCEROL
      PHOSPHATE LYASE (IGL). The Bx1 gene is under developmental control and is mainly
      responsible for BX production, whereas the Igl gene is inducible by stress
      signals, such as wounding, herbivory, or jasmonates. To determine the role of BXs
      in defense against aphids and fungi, we compared basal resistance between Bx1
      wild-type and bx1 mutant lines in the igl mutant background, thereby preventing
      BX production from IGL. Compared to Bx1 wild-type plants, BX-deficient bx1 mutant
      plants allowed better development of the cereal aphid Rhopalosiphum padi, and
      were affected in penetration resistance against the fungus Setosphaeria turtica.
      At stages preceding major tissue disruption, R. padi and S. turtica elicited
      increased accumulation of DIMBOA-glucoside, DIMBOA, and 2-hydroxy-4,7-dimethoxy
      1,4-benzoxazin-3-one-glucoside (HDMBOA-glc), which was most pronounced in
      apoplastic leaf extracts. Treatment with the defense elicitor chitosan similarly
      enhanced apoplastic accumulation of DIMBOA and HDMBOA-glc, but repressed
      transcription of genes controlling BX biosynthesis downstream of BX1. This
      repression was also obtained after treatment with the BX precursor indole and
      DIMBOA, but not with HDMBOA-glc. Furthermore, BX-deficient bx1 mutant lines
      deposited less chitosan-induced callose than Bx1 wild-type lines, whereas
      apoplast infiltration with DIMBOA, but not HDMBOA-glc, mimicked chitosan-induced
      callose. Hence, DIMBOA functions as a defense regulatory signal in maize innate
      immunity, which acts in addition to its well-characterized activity as a biocidal
      defense metabolite.

PMID- 21730200
TI  - A white spruce gene catalog for conifer genome analyses.
AB  - Several angiosperm plant genomes, including Arabidopsis (Arabidopsis thaliana),
      rice (Oryza sativa), poplar (Populus trichocarpa), and grapevine (Vitis
      vinifera), have been sequenced, but the lack of reference genomes in gymnosperm
      phyla reduces our understanding of plant evolution and restricts the potential
      impacts of genomics research. A gene catalog was developed for the conifer tree
      Picea glauca (white spruce) through large-scale expressed sequence tag sequencing
      and full-length cDNA sequencing to facilitate genome characterizations,
      comparative genomics, and gene mapping. The resource incorporates new and
      publicly available sequences into 27,720 cDNA clusters, 23,589 of which are
      represented by full-length insert cDNAs. Expressed sequence tags, mate-pair cDNA
      clone analysis, and custom sequencing were integrated through an iterative
      process to improve the accuracy of clustering outcomes. The entire catalog spans
      30 Mb of unique transcribed sequence. We estimated that the P. glauca nuclear
      genome contains up to 32,520 transcribed genes owing to incomplete, partially
      sequenced, and unsampled transcripts and that its transcriptome could span up to
      47 Mb. These estimates are in the same range as the Arabidopsis and rice
      transcriptomes. Next-generation methods confirmed and enhanced the catalog by
      providing deeper coverage for rare transcripts, by extending many incomplete
      clusters, and by augmenting the overall transcriptome coverage to 38 Mb of unique
      sequence. Genomic sample sequencing at 8.5% of the 19.8-Gb P. glauca genome
      identified 1,495 clusters representing highly repeated sequences among the cDNA
      clusters. With a conifer transcriptome in full view, functional and protein
      domain annotations clearly highlighted the divergences between conifers and
      angiosperms, likely reflecting their respective evolutionary paths.

PMID- 21730201
TI  - Abstract art: how to write competitive conference and journal abstracts.

PMID- 21730202
TI  - Professional coaching: an innovative and promising leadership development and
      career enhancement approach for public health professionals.

PMID- 21730203
TI  - Induction of human beta-defensins and psoriasin in vulvovaginal human
      papillomavirus-associated lesions.
AB  - BACKGROUND: Infections with a low-risk type of human papillomavirus (HPV) may
      lead to genital warts. HPV targets the basal cell layer of epithelial cells. The
      first line of defense is the innate immune system, which provides nonspecific
      protection against a variety of pathogens. The antimicrobial peptides (AMPs)
      alpha- and beta-defensins, cathelicidins, psoriasin, and RNase7 are central
      mediators. METHODS: The expression of various alpha- and beta-defensins,
      cathelicidin LL-37, psoriasin, and RNase7 was studied in biopsy samples from 35
      patients with genital warts and 25 healthy women using quantitative real-time
      polymerase chain reaction and immunohistochemical analysis. RESULTS: We found a
      significantly higher expression of the beta-defensins hBD-1 (P = .03), hBD-2 (P <
      0.01), and hBD-3 (P < .001), and psoriasin (P = .001) in condylomata acuminata,
      compared with normal controls. The RNA and protein levels of RNase7 did not
      differ between infected and uninfected samples (P = .55). The alpha-defensins HNP
      1-3, HD5, and HD6 and the cathelicidin LL-37 were scarcely detectable in normal
      and infected tissue. CONCLUSIONS: The differing expression of AMPs in HPV
      infected, compared with noninfected, vulvovaginal biopsy samples suggests that
      these peptides are important in the local immune response. Curiously, hBD-1 shows
      a significant induction whereas RNase7 does not, which suggests differing
      regulation of AMPs over the course of bacterial and viral infections.

PMID- 21730204
TI  - Cyanoquinolines with independent corrector and potentiator activities restore
      DeltaPhe508-cystic fibrosis transmembrane conductance regulator chloride channel
      function in cystic fibrosis.
AB  - The DeltaPhe508 mutation in the cystic fibrosis transmembrane conductance
      regulator (CFTR) protein impairs its folding, stability, and chloride channel
      gating. Although small molecules that separately correct defective DeltaPhe508
      CFTR folding/cellular processing ("correctors") or chloride channel gating
      ("potentiators") have been discovered and are in clinical trials, single
      compounds with bona fide dual corrector and potentiator activities have not been
      identified. Here, screening of ~110,000 small molecules not tested previously
      revealed a cyanoquinoline class of compounds with independent corrector and
      potentiator activities (termed CoPo). Analysis of 180 CoPo analogs revealed 6
      compounds with dual corrector and potentiator activities and 13 compounds with
      only potentiator activity. N-(2-((3-Cyano-5,7-dimethylquinolin-2-yl)amino)ethyl)
      3-methoxybenzamide (CoPo-22), which was synthesized in six steps in 52% overall
      yield, had low micromolar EC(50) for DeltaPhe508-CFTR corrector and potentiator
      activities by short-circuit current assay. Maximal corrector and potentiator
      activities were comparable with those conferred by the bithiazole Corr-4a and the
      flavone genistein, respectively. CoPo-22 also activated wild-type and G551D CFTR
      chloride conductance within minutes in a forskolin-dependent manner. Compounds
      with dual corrector and potentiator activities may be useful for single-drug
      treatment of cystic fibrosis caused by DeltaPhe508 mutation.

PMID- 21730205
TI  - Back in style?

PMID- 21730206
TI  - Effect of gender and sports on the risk of full-thickness articular cartilage
      lesions in anterior cruciate ligament-injured knees: a nationwide cohort study
      from Sweden and Norway of 15 783 patients.
AB  - BACKGROUND: The presence of an articular cartilage lesion in anterior cruciate
      ligament-injured knees is considered a predictor of osteoarthritis. PURPOSE: This
      study was undertaken to evaluate risk factors for full-thickness articular
      cartilage lesions in anterior cruciate ligament-injured knees, in particular the
      role of gender and the sport causing the initial injury. STUDY DESIGN: Cohort
      study (prognosis); Level of evidence, 2. METHODS: Primary unilateral anterior
      cruciate ligament reconstructions prospectively registered in the Swedish and the
      Norwegian National Knee Ligament Registry during 2005 through 2008 were included
      (N = 15 783). Logistic regression analyses were used to evaluate risk factors for
      cartilage lesions. RESULTS: A total of 1012 patients (6.4%) had full-thickness
      cartilage lesions. The median time from injury to surgery was 9 months (range, 0
      days-521 months). Male patients had an increased odds of full-thickness cartilage
      lesions compared with females (odds ratio = 1.22; 95% confidence interval, 1.04
      1.42). In males, team handball had an increase in the odds of full-thickness
      cartilage lesions compared with soccer (odds ratio = 2.36; 95% confidence
      interval, 1.33-4.19). Among female patients, no sport investigated showed a
      significant decrease or increase in the odds of full-thickness cartilage lesions.
      The odds of a full-thickness cartilage lesion increased by 1.006 (95% confidence
      interval, 1.005-1.008) for each month elapsed from time of injury until anterior
      cruciate ligament reconstruction when all patients were considered, while time
      from injury to surgery did not affect the odds significantly in those patients
      reconstructed within 1 year of injury (odds ratio = 0.98; 95% confidence
      interval, 0.95-1.02). Previous surgery increased the odds of having a full
      thickness cartilage lesion (odds ratio = 1.40; 95% confidence interval, 1.21
      1.63). One year of increasing patient age also increased the odds (odds ratio =
      1.05; 95% confidence interval, 1.05-1.06). CONCLUSION: Male gender is associated
      with an increased risk of full-thickness articular cartilage lesions in anterior
      cruciate ligament-injured knees. Male team handball players had an increased risk
      of full-thickness lesions. No other sports investigated were found to have
      significant effect on the risk in either gender. Furthermore, age, previous
      surgery, and time from injury to surgery exceeding 12 months are risk factors for
      full-thickness cartilage lesions.

PMID- 21730208
TI  - Closing the gap between bench and bedside research for early arthritis therapies
      (EARTH): report from the AOSSM/NIH U-13 Post-Joint Injury Osteoarthritis
      Conference II.
AB  - This report summarizes the 2010 AOSSM/NIH (American Orthopaedic Society for
      Sports Medicine/National Institutes of Health) U13 Post-Joint Injury
      Osteoarthritis II Conference to include the discussion concerning potential study
      cohorts, assessment considerations, and research priorities. There was strong
      consensus and enthusiasm for approaching the development of disease-modifying
      treatments for osteoarthritis through study of "pre-osteoarthritic" cohorts,
      particularly human subjects under 30 years of age following acute anterior
      cruciate ligament injuries. Clinical study of acute treatment strategies
      initiated within a few days after injury will need development of recruitment
      pathways and short-term proof-of-concept outcome measures that are specific to
      the intervention being studied. For example, measures of joint inflammation can
      be used in short-term prospective randomized controlled trials to determine
      whether an anti-inflammatory intervention was effective in decreasing early
      inflammation. These short-term clinical trials will need to be followed by longer
      term evaluation of the clinical cohorts for joint and cartilage degeneration to
      determine if the acute intervention affected later development of osteoarthritis.
      Research priorities were identified in several disciplines, particularly
      regarding development and validation of quantitative imaging, biomechanics, and
      biomarker measures of joint structure, composition, and function that predict the
      accelerated development of osteoarthritis. Systematic study of posttraumatic
      osteoarthritis is anticipated to advance understanding and treatment of all forms
      of osteoarthritis.

PMID- 21730207
TI  - The clinical utility and diagnostic performance of magnetic resonance imaging for
      identification of early and advanced knee osteoarthritis: a systematic review.
AB  - BACKGROUND: Current diagnostic strategies for detection of structural articular
      cartilage abnormalities, the earliest structural signs of osteoarthritis, often
      do not capture the condition until it is too far advanced for the most potential
      benefit of noninvasive interventions. PURPOSE: To systematically review the
      literature relative to the following questions: (1) Is magnetic resonance imaging
      (MRI) a valid, sensitive, specific, accurate, and reliable instrument to identify
      knee articular cartilage abnormalities compared with arthroscopy? (2) Is MRI a
      sensitive tool that can be utilized to identify early cartilage degeneration?
      STUDY DESIGN: Systematic review. METHODS: A systematic search was performed in
      November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus
      (from 1985), SCOPUS (from 1996), and EMBASE (from 1974) databases. RESULTS:
      Fourteen level I and 13 level II studies were identified that met inclusion
      criteria and provided information related to diagnostic performance of MRI
      compared with arthroscopic evaluation. The diagnostic performance of MRI
      demonstrated a large range of sensitivities, specificities, and accuracies. The
      sensitivity for identifying articular cartilage abnormalities in the knee joint
      was reported between 26% and 96%. Specificity and accuracy were reported between
      50% and 100% and between 49% and 94%, respectively. The sensitivity, specificity,
      and accuracy for identifying early osteoarthritis were reported between 0% and
      86%, 48% and 95%, and 5% and 94%, respectively. As a result of inconsistencies
      between imaging techniques and methodological shortcomings of many of the
      studies, a meta-analysis was not performed, and it was difficult to fully
      synthesize the information to state firm conclusions about the diagnostic
      performance of MRI. CONCLUSION: There is evidence in some MRI protocols that MRI
      is a relatively valid, sensitive, specific, accurate, and reliable clinical tool
      for identifying articular cartilage degeneration. Because of heterogeneity of MRI
      sequences, it is not possible to make definitive conclusions regarding its global
      clinical utility for guiding diagnosis and treatment strategies. CLINICAL
      RELEVANCE: Traumatic sports injuries to the knee may be significant precursor
      events to early onset of posttraumatic osteoarthritis. Magnetic resonance imaging
      may aid in early identification of structural injuries to articular cartilage as
      evidenced by articular cartilage degeneration grading.

PMID- 21730209
TI  - A comparison of laboratory values in pediatric hemodialysis patients: does day of
      the week matter?
AB  - BACKGROUND: The National Kidney Foundation Dialysis Outcomes Quality Initiative
      (NKF-K/DOQI) guidelines recommend the delivered dose of hemodialysis (HD) be
      measured no less than monthly by checking Kt/V (K is effective urea clearance, t
      is minute and V is urea distribution). To date, no studies have explored whether
      the day of the week for checking maintenance HD laboratory studies impacts
      dialysis dosing. METHODS: Data were collected at two HD facilities on 19
      patients, ages <= 21 years receiving maintenance HD thrice weekly over a
      consecutive 6-month period. Data obtained from the Monday and Wednesday of each
      full third week of the month included dialysis vintage, ultrafiltration volume,
      serum electrolytes, hemoglobin and clearances. RESULTS: Kt/V and K+ were
      significantly different between Monday and Wednesday (P = 0.013 and P = 0.047,
      respectively). CONCLUSION: Due to variability in values based on the day of
      laboratory evaluations, the dialysis provider must consider the impact of this on
      the quality of patient care when prescribing dialysis. Research on a larger scale
      needs to be conducted to allow for better decision-making capabilities in the
      chronic HD population.

PMID- 21730210
TI  - Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with
      secondary hyperparathyroidism.
AB  - BACKGROUND: Elevated fibroblast growth factor 23 (FGF23) is associated with
      adverse clinical outcomes and development of secondary hyperparathyroidism (SHPT)
      refractory to active vitamin D. Cinacalcet hydrochloride is effective in treating
      SHPT, but little is known as to whether treatment with cinacalcet alters these
      levels and whether pretreatment FGF23 levels predict response to this therapy.
      METHODS: We measured serum full-length FGF23 levels in 55 haemodialysis patients,
      who participated and completed the 52-week, multicentre, open-label single-arm
      trial that examined the effectiveness of cinacalcet for treating SHPT. In the
      study, alteration of vitamin D dosage was not permitted except for the case in
      which serum calcium could not be managed by calcium carbonate adjustment alone.
      RESULTS: After 12 weeks of cinacalcet treatment, FGF23 levels decreased
      significantly concomitantly with a significant reduction in intact parathyroid
      hormone (PTH) levels. These responses were sustained >52 weeks. In multivariate
      regression analyses, changes from baseline in serum FGF23 were associated with
      changes in serum calcium and phosphorus but not with intact PTH at each time
      point of measurements (Week-12, Week-24 and Week-52). Baseline FGF23 was not
      associated with the likelihood of achieving an intact PTH <180 pg/mL at the study
      end. CONCLUSIONS: Cinacalcet lowers serum FGF23 in haemodialysis patients with
      SHPT independently of the effects of active vitamin D. Pretreatment FGF23 cannot
      predict treatment response to cinacalcet in this setting. The precise mechanism
      of FGF23 reduction by cinacalcet and its clinical impact on outcomes in patients
      remain to be investigated.

PMID- 21730211
TI  - Protean presentation and multiple challenges of nephrocalcinosis in pregnancy
      (six pregnancies in four patients).
AB  - BACKGROUND: Nephrocalcinosis is an umbrella term covering increased content of
      calcium salts in the renal parenchyma, interstitial damage and potential
      evolution towards renal failure. Pregnancy is often the first occasion for
      biochemical or imaging tests in young women and may allow early diagnosis.
      Conversely, even mild kidney disease may represent a challenge in pregnancy. AIM:
      The aim of this study was to report on four patients in whom nephrocalcinosis was
      first diagnosed during pregnancy, exemplifying the protean presentation and
      multiple challenges of nephrocalcinosis in pregnancy. METHODS: This is a case
      series study including data on all pregnancies prospectively gathered in the
      Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (2000
      11). RESULTS: Six pregnancies were observed in four patients (31-35 years; one
      twin pregnancy, one ongoing, one patient with three pregnancies). Symptoms were
      oedema in two (later developed in a further patient), renal functional impairment
      and electrolyte imbalance in two each. Two patients developed hypertension late
      in pregnancy. Electrolyte imbalance was life-threatening in one patient (severe
      acidosis, severe hyperkalaemia: 7.5 mEq/L). Delivery was by Caesarean section in
      three patients, preterm in one. Multiple or long hospitalizations for metabolic
      reasons were needed in three patients, the fourth was hospitalized for obstetric
      reasons. In all patients, diagnosis of nephrocalcinosis was made at ultrasounds
      during basic nephrological evaluation, confirmed at computerized tomography scan
      in three. The pathogenesis was linked to diuretic abuse in one case and to
      collagen disease, inborn errors and prematurity, possibly associated with
      diuretic misuse, in the others. CONCLUSION: Nephrocalcinosis may have protean
      presentations in pregnancy. The risk of severe electrolyte derangements, oedema
      and hypertension warrants strict clinical surveillance.

PMID- 21730212
TI  - Prices, volume, and the perverse effects of the variations crusade. Point.

PMID- 21730213
TI  - Competitive pricing and the challenge of cost control in medicare.
AB  - The Medicare program faces a serious challenge: it must find ways to control
      costs but must do so through a system of congressional oversight that necessarily
      limits its choices. We look at one approach to prudent purchasing - competitive
      pricing - that Medicare has attempted many times and in various ways since the
      beginning of the program, and in all but one case unsuccessfully due to the
      politics of provider opposition working through Congress and the courts. We look
      at some related efforts to change Medicare pricing to explore when the program
      has been successful in making dramatic changes in how it pays for health care. A
      set of recommendations emerges for ways to respond to the impediments of law and
      politics that have obstructed change to more efficient payment methods. Except in
      unusual cases, competitive pricing threatens too many stakeholders in too many
      ways for key political actors to support it. But an unusual case may arise in the
      coming Medicare fiscal crisis, a crisis related in part to the prices Medicare
      pays. At that point, competitive pricing may look less like a problem and more
      like a solution coming at a time when the system badly needs one.

PMID- 21730214
TI  - Understanding prices and quantities in the U.S. health care system. Counterpoint.

PMID- 21730215
TI  - JHPPL's point-counterpoint section.

PMID- 21730216
TI  - Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis
      of randomized, controlled studies.
AB  - OBJECTIVES: Many randomized controlled trials (RCTs) have assessed the effects of
      soy protein on serum lipoprotein risk factors for coronary heart disease (CHD).
      This review and meta-analysis assessed the quality of these RCTs and estimated
      the effects of soy protein consumption on serum lipoproteins. DATA SOURCES: A
      comprehensive search using multiple databases was conducted for the years 1996
      through 2008 to identify clinical trials related to soy protein intake and serum
      lipoprotein changes. STUDY ELIGIBILITY: RCTs were assessed that met these
      requirements: soy protein intake compared with nonsoy protein, provided
      information on serum low-density lipoprotein (LDL)-cholesterol values, provided
      no more than 65 g of soy protein daily, and obtained LDL-cholesterol measurements
      between 4 and 18 weeks of treatment. Randomized parallel and crossover studies
      were evaluated. METHODS: Studies were graded for quality using 12 criteria with a
      possible maximum grade of 24. Net changes in lipoproteins with soy protein
      consumption compared with nonsoy control diets were analyzed by meta-analyses and
      funnel plots. Confidence intervals were constructed using inverse weighting.
      Analyses compared parallel to crossover studies and studies with lower and higher
      grades. RESULTS: Analyses included 20 parallel-design studies and 23 crossover
      studies. Parallel studies scored significantly higher (p < 0.001) in study
      quality, with a mean grade of 15.8 (95% confidence interval [CI], 14.3 to 17.3)
      compared with 10.1 (95% CI, 8.2 to 11.9) for crossover trials. Soy protein intake
      was associated with net changes in serum LDL-cholesterol values of -0.23 mmol/l
      (95% CI, -0.28 to -0.18 mmol/l) or a 5.5% reduction in parallel studies and -0.16
      mmol/l (95% CI, -0.22 to -0.11 mmol/l) or a reduction of 4.2% with crossover
      studies (p < 0.001 for parallel vs crossover). In parallel studies, net serum HDL
      cholesterol values were 3.2% higher (p < 0.007) with soy vs control, and fasting
      serum triacylglycerol values were 10.7% lower (p < 0.008) for soy vs control.
      CONCLUSIONS AND IMPLICATIONS: Soy protein consumption with a median of 30 g/d was
      associated with a significant improvement in lipoprotein risk factors for CHD.
      Compared with crossover RCTs, parallel RCTs had significantly higher quality
      grades and were associated with significantly greater improvements in serum LDL
      cholesterol values. Regular consumption of 1 to 2 servings of soy protein daily
      (15 to 30 g) has a significant favorable impact on serum lipoprotein risk factors
      for CHD.

PMID- 21730217
TI  - Dairy product intake and its association with body weight and cardiovascular
      disease risk factors in a population in dietary transition.
AB  - OBJECTIVE: Higher dairy product intake has shown beneficial effects on body
      weight, blood pressure, type 2 diabetes, and cardiovascular disease (CVD) risk
      factors in Caucasian populations. This study evaluated dairy product intake and
      its association with body weight and CVD risk profile among a population
      undergoing a dietary transition in Canada, the Nunavik Inuit. METHODS: Data were
      collected from August 27 to October 1, 2004, in the 14 villages of Nunavik on a
      Canadian research icebreaker (Canadian Coast Guard ship Amundsen). Dairy product
      intake and calcium intake were evaluated in 543 Inuit using a food frequency
      questionnaire. Physiological (lipid profile, fasting glucose, and insulin) and
      anthropometrical measurements were also obtained. RESULTS: The range of median
      dairy product intake extended from 120 g/d in the lowest tertile to 290 g/d in
      the highest tertile. The median of calcium intake was 524 mg/d. Participants in
      the highest tertile of dairy product consumption had higher body weight, fat-free
      mass, waist circumference, waist-to-hip ratio, and fasting glucose concentrations
      than participants in the lowest tertile (all p < 0.01). After adjustments for
      potential cofactors, no significant association was observed. A higher prevalence
      of Inuit participants with metabolic syndrome was observed in the higher tertile
      compared with the first tertile (10.3% vs 1.6%; p < 0.001). CONCLUSIONS: Higher
      dairy product intake in Nunavik Inuit is not related to protective effects on
      body weight and CVD. The consumption of dairy products in Nunavik Inuit is
      probably not sufficient to withdraw beneficial effects on body weight or CVD risk
      factors, as observed in North American populations.

PMID- 21730218
TI  - E-KINDEX: a dietary screening tool to assess children's obesogenic dietary
      habits.
AB  - BACKGROUND: To date, no published dietary indices have evaluated the overall
      effects of various dietary components, beliefs, and practices on the development
      of obesity in children. OBJECTIVE: To develop a dietary index that contains
      dietary characteristics and practices implicated in the development of obesity.
      METHODS: The proposed index (i.e., the E-KINDEX [Electronic Kids Dietary Index])
      incorporates 3 subindices: (1) a food groups intake index (13 items), (2) an
      index related to eating beliefs and behaviors (8 items), and (3) an index that
      evaluates dietary practices (9 items). The theoretical overall score ranges from
      1 (worst) to 87 (best). For validation of the E-KINDEX, multiple linear and
      logistic regression analyses were applied that had as dependent outcomes various
      body composition indices of 622 children (9-13 years) from the CYKIDS (Cyprus
      Kids) study. In all models, adjustments were made for age, gender, physical
      activity level, TV viewing time, socioeconomic status, breastfeeding, and
      parental obesity status. RESULTS: The highest E-KINDEX category (>60 points) was
      associated with 85% less likelihood of a child being obese or overweight (odds
      ratio [OR], 0.15; 95% confidence interval [CI], 0.05-0.41) and 86% less
      likelihood of having a waist circumference >=75th percentile (OR, 0.14; 95% CI,
      0.05-0.43). The correct classification rate of E-KINDEX (C-statistic) against
      excess body fat percentage was 84% (CI, 0.74-0.94). Moreover, for a single SD
      increase in the index score (i.e., 7.81 units), a decrease of 2.31 +/- 0.23
      kg/m(2) in body mass index (BMI), of 2.23 +/- 0.35 in percent of body fat (BF%),
      and of 2.16 +/- 0.61 cm in waist circumference was observed. Similar results were
      found during 1-year follow-up of study participants. In particular, baseline E
      KINDEX levels were inversely associated with children's BMI at 1-year follow-up
      (p = 0.024). Latent class analysis showed that the index has good discriminative
      value for only 68% of the total sample. CONCLUSION: The proposed E-KINDEX could
      be helpful in dietary assessment and in further research in the field of
      childhood obesity.

PMID- 21730219
TI  - Glycemic index and glycemic load used in combination to characterize metabolic
      responses of mixed meals in healthy lean young adults.
AB  - BACKGROUND: Glycemic index (GI) and glycemic load (GL) have been independently
      assessed with regard to their metabolic effects and their associations with
      disease risk. Because a low-GI high-carbohydrate and a high-GI low-carbohydrate
      food/meal can produce the same GL, we propose that these 2 concepts should be
      used in conjunction to characterize the carbohydrate quality of mixed meals.
      OBJECTIVE: The aim of this study was to measure postprandial glucose, insulin,
      and cortisol responses of meals differing in both GI and GL over a period of 3
      hours (every 15 minutes for the first hour, and every 30 minutes subsequently),
      and to investigate the validity of methods of calculating GI and GL by measuring
      the cumulative incremental area under the curve (iAUC) for glucose and insulin (0
      2 hours and 2-3 hours postprandially). METHODS: A total of 10 healthy lean young
      adults (5 males, 5 females) participated. Breakfast meals were designed to differ
      in terms of GI and GL based on a 2 * 2 grid with a single elaboration: low-GI
      high-GL (M1); high-GI high-GL (M2a) of similar GL to M1; high-GI high-GL (M2b) of
      similar macronutrient composition to M1 (the elaboration); low-GI low-GL (M3);
      and high-GI low-GL (M4). The 5 breakfast meals were administered in a double
      blind randomized crossover design. Repeated measures analysis of variance was
      performed to investigate differences in metabolic response between low- versus
      high-GI and between low- versus high-GL breakfast meals (and GI * GL
      interactions), with GI and GL used as within-subject factors. RESULTS: High-GL
      meals increased glucose iAUC and insulin iAUC in both immediate (0-2 hours) (p <
      0.01, p < 0.001, respectively) and middle postabsorptive periods (2-3 hours) (p =
      0.04, p = 0.02, respectively) compared with low-GL meals. GI meals were not
      associated with glucose iAUC 0 to 2 hours (p = 0.37) and 2 to 3 hours (p = 0.81)
      postprandially. GI meals were not associated with insulin iAUC 0 to 2 hours
      postprandially (p = 0.81); in contrast, high-GI meals increased insulin iAUC 2 to
      3 hours postprandially (p = 0.03) compared with low-GI meals. No significant
      differences were noted in cortisol responses, GI * GL interactions, or effect
      modification by gender. CONCLUSIONS: These findings highlight the need for
      further investigation of meals/diets differing in both GI and GL to characterize
      metabolic responses and potential health effects.

PMID- 21730220
TI  - The body image, weight satisfaction, and eating disorder tendency of school
      children: the 2-year follow-up study.
AB  - OBJECTIVE: This 2-year follow-up study was conducted to enhance our understanding
      of changes and rates of disturbed eating attitudes/behaviors, weight
      satisfaction, and prevalence of obesity in elementary school students between the
      ages of 10 and 12 years. METHODS: Questionnaires consisted of the following
      sections: (A) Demographics, (B) Body image, (C) Pubertal Development Scale, and
      (D) Children's Eating Attitudes Test-26 (ChEAT-26). School-based randomly
      selected participants completed the questionnaire at 10 years of age and repeated
      the same questionnaire 2 years later, at 12 years of age. RESULTS: The following
      findings were reported: (1) when changes at 2 years were compared, it was seen
      that the actual body weight of boys tended to increase, and perceived body size
      and desired body weight showed significant changes; (2) the percentage of
      children who wanted to be thinner increased, especially among girls; and (3) the
      percentage of participants with a tendency toward eating disorders (measured by
      ChEAT-26, >=20) decreased from 10.4% to 10.1% in boys, and increased from 10.9%
      to 12.3% in girls. CONCLUSION: Nutritional education should emphasize the
      importance of correct body image and eating attitudes for the prevention of
      unhealthy body weight concerns and eating disorders in children. Caregivers'
      attitudes about weight and how caregivers deliver information on weight issues to
      children should be recognized as important factors related to healthy body image
      and eating attitudes among children.

PMID- 21730221
TI  - The effect of birth weight on low-energy diet-induced changes in body composition
      and substrate-energy metabolism in obese women.
AB  - OBJECTIVE: The objective of this study was to examine the association of birth
      weight (BW) with body composition, resting metabolic rate (RMR), nonprotein
      respiratory quotient (NPRQ), and insulin sensitivity changes after a 12-week diet
      intervention program. METHODS: A total of 78 obese (body mass index [BMI] 34.0 +/
      2.8) women aged 36.7 +/- 7 years volunteered to participate in a 12-week diet
      intervention program. We assessed body fat mass (FM), lean mass (LM), and bone
      mass (BM; measured by dual energy x-ray absorptiometry), RMR (measured by
      indirect calorimetry), fasting plasma glucose, and insulin before and after the
      intervention. We calculated BMI, FM to LM ratio (FM/LM), and HOMA-IR. BW and
      gestational age were self-reported, and the BW Z-score was calculated. RESULTS:
      At baseline, the BW Z-score was positively associated with LM (p < 0.01) and RMR
      (p < 0.05). The BW Z-score was significantly associated with diet-induced FM (p <
      0.05) and FM/LM ratio changes (p < 0.01) independently of potential confounders
      including weight loss. The BW Z-score was not associated with diet-induced RMR or
      insulin resistance changes. CONCLUSIONS: Lower birth weight is associated with
      lower LM and RMR in obese women and could program a lower FM loss achievement
      after an energy-restriction diet intervention.

PMID- 21730222
TI  - High dietary glycemic index and low fiber content are associated with metabolic
      syndrome in patients with type 2 diabetes.
AB  - OBJECTIVE: To investigate possible associations of dietary glycemic index (GI)
      and fiber content with metabolic syndrome (MetS) in patients with type 2
      diabetes. METHODS: In this cross-sectional study, 175 outpatients with type 2
      diabetes (aged 61.1 +/- 9.7 years; HbA(1c) 7.3% +/- 1.4%; diabetes duration of 11
      years [range, 5-17]) had food intake assessed by 3-day weighed-diet records.
      Dietary GI (according to FAO/WHO) and fiber content were categorized as high or
      low based on median values. MetS was defined according to the 2009 Joint Interim
      Statement. RESULTS: Patients with MetS (n = 109) had higher 24-hour GI (60.0% +/-
      6.3% vs 57.5% +/- 6.4%), higher breakfast GI (59.8% +/- 8.0% vs 55.0% +/- 9.9%),
      and lower fiber intake at 24 hours (17.0 +/- 6.6 g vs 21.2 +/- 8.0 g), breakfast
      (1.9 [1.2-3.2] vs 3.1 [1.8-4.9] g), lunch (6.2 [3.9-8.0] vs 7.5 [4.7-9.4] g), and
      dinner (3.3 [2.1-5.2] vs 4.9 [3.1-6.4] g; p < 0.05 for all comparisons) than
      patients without MetS. In multivariate analyses, high GI (~60%) of 24 hours (odds
      ratio [OR], 2.12; 95% confidence interval [CI], 1.10-4.11; p = 0.025), breakfast
      (OR, 2.20; 95% CI, 1.15-4.21; p = 0.017), and lunch (OR, 2.46; 95% CI, 1.28-4.74;
      p = 0.007) was associated with MetS. Breakfast (OR, 2.14; 95% CI, 1.04-4.41; p =
      0.039) and dinner (OR, 2.27; 95% CI, 1.15-4.49; p = 0.019) with low fiber content
      were also associated with MetS. When high GI and low fiber intake were combined
      into the same variable, associations with MetS were maintained. CONCLUSIONS:
      Increased dietary GI and reduced fiber content were positively associated with
      MetS, mainly due to breakfast intake, in patients with type 2 diabetes.

PMID- 21730223
TI  - Dietary pattern and bone density changes in elderly women: a longitudinal study.
AB  - OBJECTIVE: Few data are available on the effect of the diet in general on bone
      health. The objective of this study was to identify dietary patterns and to
      evaluate the association between such patterns and bone mineral density (BMD)
      changes over time. METHODS: We analyzed a sample of women aged >=65 years
      participating in the InCHIANTI Study. BMD was evaluated using computed tomography
      of the tibia and nutritional intake using the EPIC questionnaire. We used a
      cluster analysis to identify patterns of dietary intake. The clusters were
      compared with respect to nutritional intake; risk factors for osteoporosis;
      comorbidity; total, trabecular, and cortical BMD; and BMD changes over 6 years.
      RESULTS: The sample size was 434, with a mean age of 75.2 years (SD, 7.01 years;
      range, 65-94 years). Based on dietary variables, 2 clusters were identified with
      a marked difference in energy intake (30 kcal/kg of ideal body weight [IBW] in
      cluster 1 vs 44 kcal/kg IBW in cluster 2). We found no meaningful differences
      between clusters with regard to nondietary risk factors for osteoporosis, BMD
      measured at baseline, and changes in BMD over the 6-year follow-up; cluster 2
      showed a greater increase in cortical BMD (+30.2 mg/cm(3) vs +16.7 mg/cm(3)).
      Members of cluster 2 were less likely to have a lower cortical BMD increase
      (adjusted odds ratio, 0.452; 95% confidence interval, 0.215-0.950). CONCLUSIONS:
      Cortical BMD increases more in participants eating a diet exceeding the RDA for
      macronutrients. Cortical BMD may be more sensitive to diet and dietary
      interventions than trabecular bone.

PMID- 21730224
TI  - Action of plant sterol intervention on sterol kinetics in hypercholesterolemic
      men with high versus low basal circulatory plant sterol concentrations.
AB  - BACKGROUND: The relationship between plant sterol (PS) absorption and circulatory
      concentrations with cholesterol absorption and biosynthesis during PS consumption
      has yet to be clearly elucidated in humans. It is therefore essential to examine
      campesterol, beta-sitosterol, and cholesterol absorption and cholesterol
      fractional synthesis rate (FSR) following PS consumption in individuals with high
      versus low basal circulatory PS concentrations. DESIGN: A randomized, crossover
      trial was conducted in 82 hypercholesterolemic men consuming spreads with or
      without 2 g/d of PS for two 4-week periods, each separated by a 4-week washout.
      Endpoint tracer enrichments after ingestion of (2)H-labeled campesterol or beta
      sitosterol and (13)C-labeled cholesterol were determined by isotope ratio mass
      spectrometry. RESULTS: For both phases of dietary intervention, the endpoint
      cholesterol absorption index was positively correlated with campesterol (r =
      0.5864, p < 0.0001) and beta-sitosterol (r = 0.4676, p < 0.0001) absorption
      indices; inversely, endpoint cholesterol FSR correlated negatively with the
      absorption indices of campesterol (r = -0.5004, p < 0.0009), beta-sitosterol (r =
      -0.4154, p < 0.05), and cholesterol (r = -0.4056, p < 0.0001). PS intervention
      reduced absorption indices of campesterol, beta-sitosterol, and cholesterol by
      36.5% +/- 2.7%, 39.3% +/- 2.9%, and 34.3% +/- 1.9%, respectively, but increased
      cholesterol FSR by 33.0% +/- 3.3% relative to control. Endpoint circulatory PS
      levels (cholesterol adjusted) were positively associated with endpoint absorption
      indices of campesterol (r = 0.5586, p < 0.0001, for placebo; r = 0.6530, p <
      0.0001, for PS intake) and cholesterol (r = 0.3683, p < 0.001 for placebo; r =
      0.3469, p < 0.002, for PS intake) and were negatively associated with cholesterol
      FSR (r = -0.3551, p < 0.002, for placebo; r = -0.3643, p < 0.001, for PS intake).
      The cholesterol-lowering effect of PS was most pronounced among individuals
      falling within the 50th-75th percentiles of basal PS concentrations. CONCLUSION:
      These data suggest that basal PS concentrations indicate not only sterol
      absorption efficiency but also the extent of PS-induced cholesterol reduction and
      thus might be clinically useful to predict the extent of cholesterol response to
      PS intervention within a given individual.

PMID- 21730225
TI  - The dependence of crowding on flanker complexity and target-flanker similarity.
AB  - We examined the effects of the spatial complexity of flankers and target-flanker
      similarity on the performance of identifying crowded letters. On each trial,
      observers identified the middle character of random strings of three characters
      ("trigrams") briefly presented at 10 degrees  below fixation. We tested the 26
      lowercase letters of the Times Roman and Courier fonts, a set of 79 characters
      (letters and non-letters) of the Times Roman font, and the uppercase letters of
      two highly complex ornamental fonts, Edwardian and Aristocrat. Spatial complexity
      of characters was quantified by the length of the morphological skeleton of each
      character, and target-flanker similarity was defined based on a psychometric
      similarity matrix. Our results showed that (1) letter identification error rate
      increases with flanker complexity up to a certain value, beyond which error rate
      becomes independent of flanker complexity; (2) the increase of error rate is
      slower for high-complexity target letters; (3) error rate increases with target
      flanker similarity; and (4) mislocation error rate increases with target-flanker
      similarity. These findings, combined with the current understanding of the faulty
      feature integration account of crowding, provide some constraints of how the
      feature integration process could cause perceptual errors.

PMID- 21730226
TI  - Association of the Alzheimer's gene SORL1 with hippocampal volume in young,
      healthy adults.
AB  - OBJECTIVE: Alzheimer's disease is among the most common neurodegenerative
      disorders. The SORL1 (sortilin receptor 1) gene is associated with the disease,
      but different variants seem to contribute. The authors used a gene-wide approach
      to test whether SORL1 is associated with volume of the hippocampus, one of the
      first structures to be affected by Alzheimer's disease in young, healthy
      individuals, in an attempt to map potential pathways from gene to disease.
      METHOD: Individuals were genotyped using an array-based method, and a total of
      117 single nucleotide polymorphisms (SNPs) in and surrounding SORL1 were included
      in the analysis. Through the use of a brain segmentation protocol, SNP-by-SNP and
      gene-wide associations with bilateral hippocampal volume were assessed in two
      large, independent samples consisting of 446 (discovery cohort) and 490
      (replication cohort) healthy young individuals. RESULTS: Significant association
      of the SORL1 gene with hippocampal volume was observed in both the discovery and
      replication samples as well as in the combined sample. The gene-wide association
      was independent of the apolipoprotein E genotype and resistant to removal of four
      significantly associated single SNPs. CONCLUSIONS: This study provides the first
      evidence that the SORL1 gene is associated with differences in hippocampal volume
      in young, healthy adults. It is demonstrated that gene-wide analysis techniques
      may overcome power problems caused by allelic heterogeneity in association
      studies. The results support the hypothesis that the SORL1 gene contributes to an
      increased risk for Alzheimer's disease through effects on hippocampal volume.

PMID- 21730228
TI  - Screening for HIV infection: a healthy, "low-risk" 42-year-old man.
AB  - Human immunodeficiency virus (HIV) infection meets many, if not all, of the
      established criteria that justify routine screening, and screening for HIV
      infection can be cost-effective depending on the population studied. In 2006, the
      Centers for Disease Control and Prevention recommended that HIV screening be
      included as part of routine care for most of the adult US population, but
      implementation of this policy has been slow. Mr Y is a 42-year-old man at
      relatively low risk of HIV infection who was offered testing by his primary care
      physician but declined it. He does not consider HIV infection to be a realistic
      possibility given his behavioral history and does not understand the purpose of
      being tested. The discussion that follows addresses the rationale for HIV
      screening, its potential benefits and risks, current testing options, and
      barriers to incorporating it into routine care.

PMID- 21730229
TI  - Dietary supplements--regulatory issues and implications for public health.

PMID- 21730230
TI  - The cover. Catching whitebait at Nakaumi, Izumo Province (Nakaumi Shira-uo Tori).

PMID- 21730231
TI  - A piece of my mind. The silent majority.

PMID- 21730232
TI  - Research aims to boost pertussis control.

PMID- 21730233
TI  - Rare E. coli strain races through Europe; high rate of kidney failure reported.

PMID- 21730234
TI  - Myocardial enzyme levels and mortality after coronary artery bypass graft
      surgery.

PMID- 21730235
TI  - Myocardial enzyme levels and mortality after coronary artery bypass graft
      surgery.

PMID- 21730236
TI  - Hydrocortisone and treatment of multiple trauma.

PMID- 21730237
TI  - Hydrocortisone and treatment of multiple trauma.

PMID- 21730238
TI  - Hydrocortisone and treatment of multiple trauma.

PMID- 21730239
TI  - Fifteen-year follow-up of association between telomere length and incident cancer
      and cancer mortality.

PMID- 21730240
TI  - Quality of care and patient outcomes in critical access rural hospitals.
AB  - CONTEXT: Critical access hospitals (CAHs) play a crucial role in the US rural
      safety net. Current policy efforts have focused primarily on helping these small,
      isolated hospitals remain financially viable to ensure access for individuals
      living in rural areas in the United States; however, little is known about the
      quality of care they provide or the outcomes their patients achieve. OBJECTIVES:
      To examine the quality of care and patient outcomes at CAHs and to understand why
      patterns of care might differ for CAHs vs non-CAHs. DESIGN, SETTING, AND
      PATIENTS: A retrospective analysis in 4738 US hospitals of Medicare fee-for
      service beneficiaries with acute myocardial infarction (AMI) (10,703 for CAHs vs
      469,695 for non-CAHs), congestive heart failure (CHF) (52,927 for CAHs vs 958,790
      for non-CAHs), and pneumonia (86,359 for CAHs vs 773,227 for non-CAHs) who were
      discharged in 2008-2009. MAIN OUTCOME MEASURES: Clinical capabilities,
      performance on processes of care, and 30-day mortality rates, adjusted for age,
      sex, race, and medical comorbidities. RESULTS: Compared with other hospitals (n =
      3470), 1268 CAHs (26.8%) were less likely to have intensive care units (380
      [30.0%] vs 2581 [74.4%], P < .001), cardiac catheterization capabilities (6
      [0.5%] vs 1654 [47.7%], P < .001), and at least basic electronic health records
      (80 [6.5%] vs 445 [13.9%], P < .001). The CAHs had lower performance on processes
      of care than non-CAHs for all 3 conditions examined (concordance with Hospital
      Quality Alliance process measures for AMI, 91.0% [95% CI, 89.7%-92.3%] vs 97.8%
      [95% CI, 97.7%-97.9%]; for CHF, 80.6% [95% CI, 79.2%-82.0%] vs 93.5% [95% CI,
      93.3%-93.7%]; and for pneumonia, 89.3% [95% CI, 88.6%-90.0%] vs 93.7% [95% CI,
      93.6%-93.9%]; P < .001 for each). Patients admitted to CAHs had higher 30-day
      mortality rates for each condition than those admitted to non-CAHs (for AMI:
      23.5% vs 16.2%; adjusted odds ratio [OR], 1.70; 95% confidence interval [CI],
      1.61-1.80; P < .001; for CHF: 13.4% vs 10.9%; adjusted OR, 1.28; 95% CI, 1.23
      1.32; P < .001; and for pneumonia: 14.1% vs 12.1%; adjusted OR, 1.20; 95% CI,
      1.16-1.24; P < .001). CONCLUSION: Compared with non-CAHs, CAHs had fewer clinical
      capabilities, worse measured processes of care, and higher mortality rates for
      patients with AMI, CHF, or pneumonia.

PMID- 21730241
TI  - Appropriateness of percutaneous coronary intervention.
AB  - CONTEXT: Despite the widespread use of percutaneous coronary intervention (PCI),
      the appropriateness of these procedures in contemporary practice is unknown.
      OBJECTIVE: To assess the appropriateness of PCI in the United States. DESIGN,
      SETTING, AND PATIENTS: Multicenter, prospective study of patients within the
      National Cardiovascular Data Registry undergoing PCI between July 1, 2009, and
      September 30, 2010, at 1091 US hospitals. The appropriateness of PCI was
      adjudicated using the appropriate use criteria for coronary revascularization.
      Results were stratified by whether the procedure was performed for an acute (ST
      segment elevation myocardial infarction, non-ST-segment elevation myocardial
      infarction, or unstable angina with high-risk features) or nonacute indication.
      MAIN OUTCOME MEASURES: Proportion of acute and nonacute PCIs classified as
      appropriate, uncertain, or inappropriate; extent of hospital-level variation in
      inappropriate procedures. RESULTS: Of 500,154 PCIs, 355,417 (71.1%) were for
      acute indications (ST-segment elevation myocardial infarction, 103,245 [20.6%];
      non-ST-segment elevation myocardial infarction, 105,708 [21.1%]; high-risk
      unstable angina, 146,464 [29.3%]), and 144,737 (28.9%) for nonacute indications.
      For acute indications, 350,469 PCIs (98.6%) were classified as appropriate, 1055
      (0.3%) as uncertain, and 3893 (1.1%) as inappropriate. For nonacute indications,
      72,911 PCIs (50.4%) were classified as appropriate, 54,988 (38.0%) as uncertain,
      and 16,838 (11.6%) as inappropriate. The majority of inappropriate PCIs for
      nonacute indications were performed in patients with no angina (53.8%), low-risk
      ischemia on noninvasive stress testing (71.6%), or suboptimal (<=1 medication)
      antianginal therapy (95.8%). Furthermore, although variation in the proportion of
      inappropriate PCI across hospitals was minimal for acute procedures, there was
      substantial hospital variation for nonacute procedures (median hospital rate for
      inappropriate PCI, 10.8%; interquartile range, 6.0%-16.7%). CONCLUSIONS: In this
      large contemporary US cohort, nearly all acute PCIs were classified as
      appropriate. For nonacute indications, however, 12% were classified as
      inappropriate, with substantial variation across hospitals.

PMID- 21730242
TI  - Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death among
      women.
AB  - CONTEXT: Sudden cardiac death (SCD) accounts for more than half of all cardiac
      deaths; the majority of SCD events occur as the first manifestation of heart
      disease, especially among women. Primary preventive strategies are needed to
      reduce SCD incidence. OBJECTIVE: To estimate the degree to which adherence to a
      healthy lifestyle may lower the risk of SCD among women. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective cohort study of 81,722 US women in the Nurses' Health
      Study from June 1984 to June 2010. Lifestyle factors were assessed via
      questionnaires every 2 to 4 years. A low-risk lifestyle was defined as not
      smoking, body mass index of less than 25, exercise duration of 30 minutes/day or
      longer, and top 40% of the alternate Mediterranean diet score, which emphasizes
      high intake of vegetables, fruits, nuts, legumes, whole grains, and fish and
      moderate intake of alcohol. MAIN OUTCOME MEASURE: Sudden cardiac death (defined
      as death occurring within 1 hour after symptom onset without evidence of
      circulatory collapse). RESULTS: There were 321 cases of SCD during 26 years of
      follow-up. Women were a mean age of 72 years at the time of the SCD event. All 4
      low-risk lifestyle factors were significantly and independently associated with a
      lower risk of SCD. The absolute risks of SCD were 22 cases/100,000 person-years
      among women with 0 low-risk factors, 17 cases/100,000 person-years with 1 low
      risk factor, 18 cases/100,000 person-years with 2 low-risk factors, 13
      cases/100,000 person-years with 3 low-risk factors, and 16 cases/100,000 person
      years with 4 low-risk factors. Compared with women with 0 low-risk factors, the
      multivariable relative risk of SCD was 0.54 (95% confidence interval [CI], 0.34
      0.86) for women with 1 low-risk factor, 0.41 (95% CI, 0.25-0.65) for 2 low-risk
      factors, 0.33 (95% CI, 0.20-0.54) for 3 low-risk factors, and 0.08 (95% CI, 0.03
      0.23) for 4 low-risk factors. The proportion of SCD attributable to smoking,
      inactivity, overweight, and poor diet was 81% (95% CI, 52%-93%). Among women
      without clinically diagnosed coronary heart disease, the percentage of population
      attributable risk was 79% (95% CI, 40%-93%). CONCLUSION: Adherence to a low-risk
      lifestyle is associated with a low risk of SCD.

PMID- 21730244
TI  - Update: A 39-year-old man with HIV-associated lipodystrophy.

PMID- 21730245
TI  - Clinical decision support and malpractice risk.

PMID- 21730246
TI  - Application of electronic health records to the Joint Commission's 2011 National
      Patient Safety Goals.

PMID- 21730243
TI  - Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal
      dysfunction among uninfected infants of HIV-infected mothers.
AB  - CONTEXT: Lopinavir-ritonavir is a human immunodeficiency virus 1 (HIV-1) protease
      inhibitor boosted by ritonavir, a cytochrome p450 inhibitor. A warning about its
      tolerance in premature newborns was recently released, and transient elevation of
      17-hydroxyprogesterone (17OHP) was noted in 2 newborns treated with lopinavir
      ritonavir in France. OBJECTIVE: To evaluate adrenal function in newborns
      postnatally treated with lopinavir-ritonavir. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective cross-sectional analysis of the database from the national
      screening for congenital adrenal hyperplasia (CAH) and the French Perinatal
      Cohort. Comparison of HIV-1-uninfected newborns postnatally treated with
      lopinavir-ritonavir and controls treated with standard zidovudine. MAIN OUTCOME
      MEASURES: Plasma 17OHP and dehydroepiandrosterone-sulfate (DHEA-S) concentrations
      during the first week of treatment. Clinical and biological symptoms compatible
      with adrenal deficiency. RESULTS: Of 50 HIV-1-uninfected newborns who received
      lopinavir-ritonavir at birth for a median of 30 days (interquartile range [IQR],
      25-33), 7 (14%) had elevated 17OHP levels greater than 16.5 ng/mL for term
      infants (>23.1 ng/mL for preterm) on days 1 to 6 vs 0 of 108 controls having
      elevated levels. The median 17OHP concentration for 42 term newborns treated with
      lopinavir-ritonavir was 9.9 ng/mL (IQR, 3.9-14.1 ng/mL) vs 3.7 ng/mL (IQR, 2.6
      5.3 ng/mL) for 93 term controls (P < .001). The difference observed in median
      17OHP values between treated newborns and controls was higher in children also
      exposed in utero (11.5 ng/mL vs 3.7 ng/mL; P < .001) than not exposed in utero
      (6.9 ng/mL vs 3.3 ng/mL; P = .03). The median DHEA-S concentration among 18 term
      newborns treated with lopinavir-ritonavir was 9242 ng/mL (IQR, 1347-25,986 ng/mL)
      compared with 484 ng/mL (IQR, 218-1308 ng/mL) among 17 term controls (P < .001).
      The 17OHP and DHEA-S concentrations were positively correlated (r = 0.53; P =
      .001). All term newborns treated with lopinavir-ritonavir were asymptomatic,
      although 3 premature newborns experienced life-threatening symptoms compatible
      with adrenal insufficiency, including hyponatremia and hyperkalemia with, in 1
      case, cardiogenic shock. All symptoms resolved following completion of the
      lopinavir-ritonavir treatment. CONCLUSION: Among newborn children of HIV-1
      infected mothers exposed in utero to lopinavir-ritonavir, postnatal treatment
      with a lopinavir-ritonavir-based regimen, compared with a zidovudine-based
      regimen, was associated with transient adrenal dysfunction.

PMID- 21730247
TI  - Do nice patients receive better care?

PMID- 21730248
TI  - Critical access hospitals and the challenges to quality care.

PMID- 21730249
TI  - My Vision for JAMA.

PMID- 21730250
TI  - JAMA patient page. Concussion.

PMID- 21730251
TI  - The development of an adolescent smoking cessation intervention--an Intervention
      Mapping approach to planning.
AB  - The objective of this project was to develop a theory- and evidence-based
      adolescent smoking cessation intervention using both new and existing materials.
      We used the Intervention Mapping framework for planning health promotion
      programmes. Based on a needs assessment, we identified important and changeable
      determinants of cessation behaviour, specified change objectives for the
      intervention programme, selected theoretical change methods for accomplishing
      intervention objectives and finally operationalized change methods into practical
      intervention strategies. We found that guided practice, modelling, self
      monitoring, coping planning, consciousness raising, dramatic relief and
      decisional balance were suitable methods for adolescent smoking cessation. We
      selected behavioural journalism, guided practice and Motivational Interviewing as
      strategies in our intervention. Intervention Mapping helped us to develop as
      systematic adolescent smoking cessation intervention with a clear link between
      behavioural goals, theoretical methods, practical strategies and materials and
      with a strong focus on implementation and recruitment. This paper does not
      present evaluation data.

PMID- 21730252
TI  - Effects of mass media campaign exposure intensity and durability on quit attempts
      in a population-based cohort study.
AB  - OBJECTIVE: To assess the extent to which intensity and timing of televised anti
      smoking advertising emphasizing the serious harms of smoking influences quit
      attempts. METHODS: Using advertising gross rating points (GRPs), we estimated
      exposure to tobacco control and nicotine replacement therapy (NRT) advertising in
      the 3, 4-6, 7-9 and 10-12 months prior to follow-up of a replenished cohort of
      3037 Australian smokers during 2002-08. Using generalized estimating equations,
      we related the intensity and timing of advertising exposure from each source to
      the likelihood of making a quit attempt in the 3 months prior to follow-up.
      RESULTS: Tobacco control advertising in the 3-month period prior to follow-up,
      but not in more distant past periods, was related to a higher likelihood of
      making a quit attempt. Each 1000 GRP increase per quarter was associated with an
      11% increase in making a quit attempt [odds ratio (OR) = 1.11, 95% confidence
      interval (CI) 1.03-1.19, P = 0.009)]. NRT advertising was unrelated to quit
      attempts. CONCLUSIONS: Tobacco control advertising emphasizing the serious harms
      of smoking is associated with short-term increases in the likelihood of smokers
      making a quit attempt. Repeated cycles of higher intensity tobacco control media
      campaigns are needed to sustain high levels of quit attempts.

PMID- 21730253
TI  - Is the Global Solar UV Index an effective instrument for promoting sun
      protection? A systematic review.
AB  - Exposure to ultraviolet radiation is an important risk factor for skin cancer.
      The Global Solar Ultraviolet Index (UVI) was developed as a tool to visualize the
      amount of harmful radiation and to encourage people to use sun protection. We
      conducted a systematic review of the effectiveness of the UVI. We employed a
      comprehensive search strategy to explore the impact of the UVI on five outcome
      categories. Twenty-seven of a total of 260 studies met our inclusion criteria;
      data extraction and quality appraisal were undertaken for 25 studies, comprising
      3 randomized controlled trials, 2 non-randomized intervention studies and 20
      cross-sectional studies. Nearly half of these studies were from Australia and New
      Zealand. We found low to intermediate levels of UVI awareness and low levels of
      UVI understanding. Studies rated moderate or strong suggest that the UVI does not
      influence knowledge, attitudes, sun protection behavior or sun exposure. Overall,
      the findings imply that the UVI, as currently implemented, has not been
      successful at improving sun protection practices and reducing sun exposure among
      the population at large. Drawing on experience with theory-based sun protection
      programs, we advocate for more realistic expectations of what the UVI can and
      cannot achieve.

PMID- 21730254
TI  - Effect of biomimetic remineralization on the dynamic nanomechanical properties of
      dentin hybrid layers.
AB  - The mineral and organic phases of mineralized dentin contribute co-operatively to
      its strength and toughness. This study tested the null hypothesis that there is
      no difference in nano-dynamic mechanical behavior (complex modulus-E*; loss
      modulus-E''; storage modulus-E'; in GPa) of dentin hybrid layers (baseline: E*,
      3.86 +/- 0.24; E'', 0.23 +/- 0.05; E', 3.85 +/- 0.24) created by an etch-and
      rinse adhesive in the presence or absence of biomimetic remineralization after in
      vitro aging. Using scanning probe microscopy and nano-dynamic mechanical
      analysis, we demonstrated that biomimetic remineralization restored the nano
      dynamic mechanical behavior of heavily remineralized, resin-sparse regions of
      dentin hybrid layers (E*, 19.73 +/- 3.85; E'', 8.75 +/- 3.97; E', 16.02 +/- 2.58)
      to those of the mineralized dentin base (E*, 19.20 +/- 2.42; E'', 6.57 +/- 1.96;
      E', 17.39 +/- 2.0) [p > 0.05]. Conversely, those resin-sparse, water-rich regions
      degraded in the absence of biomimetic remineralization, with significant decline
      [p < 0.05] in their complex and storage moduli (E*, 0.83 +/- 0.35; E'', 0.88 +/-
      0.24; E', 0.62 +/- 0.32). Intrafibrillar apatite deposition preserves the
      integrity of resin-sparse regions of hybrid layers by restoring their
      nanomechanical properties to those exhibited by mineralized dentin.

PMID- 21730255
TI  - Oral health and cancer, cardiovascular, and respiratory mortality of Japanese.
AB  - Cardiovascular diseases, cancer, and respiratory disease are major causes of
      death in developed countries. No study has simultaneously compared the
      contribution of oral health with these major causes of death. This study examined
      the association between oral health and cardiovascular diseases, cancer, and
      respiratory mortality among older Japanese. Self-administered questionnaires were
      mailed to participants in the Aichi Gerontological Evaluation Study (AGES)
      Project in 2003. Mortality data were analyzed for 4425 respondents. Three
      categories of oral health were used: 20 or more teeth, 19 or fewer teeth and eat
      everything, 19 or fewer teeth and eating difficulty. Sex, age, body mass index
      (BMI), self-rated health, present illness, exercise, smoking, alcohol, education,
      and income were used as covariates. During 4.28 years' follow-up, 410 people
      died, 159 from cancer, 108 of cardiovascular diseases, and 58 of respiratory
      disease. Multivariate adjusted Cox proportional hazard models showed that,
      compared with the respondents with 20 or more teeth, respondents with 19 or fewer
      teeth and with eating difficulty had a 1.83 and 1.85 times higher hazard ratio
      for cardiovascular disease mortality and respiratory disease mortality,
      respectively. There was no significant association with cancer mortality. Oral
      health predicted cardiovascular and respiratory disease mortality but not cancer
      mortality in older Japanese.

PMID- 21730257
TI  - Physiology: found in translation.

PMID- 21730256
TI  - Local inflammatory markers and systemic endotoxin in aggressive periodontitis.
AB  - While much research has focused on local and systemic factors contributing to
      periodontal disease, little is known regarding mechanisms linking these factors.
      We have previously reported a systemic hyper-inflammatory response to bacterial
      endotoxin in localized aggressive periodontitis (LAP). The objectives of this
      study were to delineate cyto/chemokines in gingival crevicular fluid (GCF) and
      evaluate systemic levels of endotoxin associated with LAP. Clinical parameters,
      GCF, and peripheral blood were collected from: 34 LAP, 10 healthy siblings, and
      nine healthy unrelated control individuals. Cyto/chemokines were quantified in
      GCF, systemic endotoxin levels were quantified in plasma, and correlation
      analysis was performed among all parameters. Nine mediators were elevated in LAP
      diseased sites as compared with healthy sites (TNFalpha, INFgamma, IL1beta, IL2,
      IL6, IL10, Il12p40, GMCSF, and MIP1alpha, p < 0.001), while MCP1, IL4, and IL8
      were elevated in healthy sites (p < 0.01). Four- to five-fold-higher endotoxin
      levels were detected in LAP plasma compared with that from healthy participants
      (p < 0.0001), which correlated with all clinical parameters and most
      cyto/chemokines analyzed. In conclusion, higher systemic levels of endotoxin were
      found in LAP, which correlates with an exacerbated local inflammatory response
      and clinical signs of disease. (Clinicaltrials.gov number, NCT01330719).

PMID- 21730258
TI  - Seasonal regulation of the growth hormone-insulin-like growth factor-I axis in
      the American black bear (Ursus americanus).
AB  - The American black bear maintains lean body mass for months without food during
      winter denning. We asked whether changes in the growth hormone/insulin-like
      growth factor-I (GH-IGF-I) axis may contribute to this remarkable adaptation to
      starvation. Serum IGF-I levels were measured by radioimmunoassay, and IGF-binding
      proteins (IGFBPs) were analyzed by ligand blotting. Initial studies in bears
      living in the wild showed that IGF-I levels are highest in summer and lowest in
      early winter denning. Detailed studies in captive bears showed that IGF-I levels
      decline in autumn when bears are hyperphagic, continue to decline in early
      denning, and later rise above predenning levels despite continued starvation in
      the den. IGFBP-2 increased and IGFBP-3 decreased in early denning, and these
      changes were also reversed in later denning. Treatment with GH (0.1 mg.kg(
      1).day(-1) * 6 days) during early denning increased serum levels of IGF-I and
      IGFBP-3 and lowered levels of IGFBP-2, indicating that denning bears remain
      responsive to GH. GH treatment lowered blood urea nitrogen levels, reflecting
      effects on protein metabolism. GH also accelerated weight loss and markedly
      increased serum levels of free fatty acids and beta-hydroxybutyrate, resulting in
      a ketoacidosis (bicarbonate decreased to 15 meq/l), which was reversed when GH
      was withdrawn. These results demonstrate seasonal regulation of GH/IGF-I axis
      activity in black bears. Diminished GH activity may promote fat storage in autumn
      in preparation for denning and prevent excessive mobilization and premature
      exhaustion of fat stores in early denning, whereas restoration of GH/IGF activity
      in later denning may prepare the bear for normal activity outside the den.

PMID- 21730259
TI  - Characterization of three IGFBP mRNAs in Atlantic croaker and their regulation
      during hypoxic stress: potential mechanisms of their upregulation by hypoxia.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) play important roles in
      downregulating IGF activity and growth and development in vertebrates under
      hypoxic stress. However, the mechanisms of hypoxia regulation of IGFBPs in
      teleost fishes are unknown. The involvement of reactive oxygen species (ROS) and
      hypoxia-inducible factors (HIFs) in hypoxia upregulation of IGFBPs in Atlantic
      croaker were investigated. Three croaker IGFBPs, IGFBP-1, IGFBP-2, and IGFBP-5,
      were cloned and characterized. Chronic hypoxia exposure [dissolved oxygen (DO):
      1.7 mg/l for 2-4 wk] caused significant increases in hepatic and neural IGFBP-1
      mRNA expression compared with tissue mRNA levels in fish held under normoxic
      conditions (6.5 mg DO/l). Moreover, longer-term chronic hypoxia exposure (2-2.7
      mg DO/l for 15-20 wk) caused significant increases in mRNA levels of all three
      IGFBPs in both liver and brain tissues. Hypoxia exposure also markedly increased
      superoxide radical (O(2)(.-), an index of ROS) production and HIF-1alpha mRNA and
      HIF-2alpha protein expression in croaker livers. Pharmacological treatment with
      an antioxidant attenuated the hypoxia-induced increases in O(2)(.-) production
      and HIFalpha mRNA and protein expression as well as the elevation of IGFBP-1 mRNA
      levels. These results suggest that the upregulation of IGFBP expression under
      hypoxia stress is due, in part, to alterations in the antioxidant status, which
      may involve ROS and HIFs.

PMID- 21730260
TI  - Insulin administration abrogates perturbation of methyl group and homocysteine
      metabolism in streptozotocin-treated type 1 diabetic rats.
AB  - Modifications in methyl group and homocysteine metabolism are associated with a
      number of pathologies, including vascular disease, cancer, and neural tube
      defects. A diabetic state is known to alter both methyl group and homocysteine
      metabolism, and glycine N-methyltransferase (GNMT) is a major regulatory protein
      that controls the supply and utilization of methyl groups. We have shown
      previously that diabetes induces GNMT expression and reduces plasma homocysteine
      pools by stimulating both its catabolism and folate-independent remethylation.
      This study was conducted to determine whether insulin plays a role in the control
      of homocysteine concentrations and GNMT as well as other key regulatory proteins.
      Male Sprague-Dawley rats were randomly assigned to one of three groups: control,
      streptozotocin (STZ)-induced diabetic (60 mg/kg body wt), and insulin-treated
      diabetic (1.0 U bid). After 5 days, rats were anesthetized (ketamine-xylazine)
      for procurement of blood and tissues. A 1.5-fold elevation in hepatic GNMT
      activity and hypohomocysteinemia in diabetic rats was completely prevented by
      insulin treatment. Additionally, diabetes-mediated alterations in methionine
      synthase, phosphatidylethanolamine N-methyltransferase, and DNA methylation were
      also prevented by insulin. We hypothesize that the concentration of blood glucose
      may represent a regulatory signal to modify GNMT and homocysteine. In support of
      this, blood glucose concentrations were negatively correlated with total plasma
      homocysteine (r = -0.75, P < 0.001) and positively correlated with GNMT activity
      (r = 0.77, P < 0.001). Future research will focus on further elucidating the role
      of glucose or insulin as a signal for regulating homocysteine and methyl group
      metabolism.

PMID- 21730261
TI  - Optical coherence tomography: has its time come?

PMID- 21730262
TI  - Pacemaker lead overcoiling: the overcoil-retraction phenomenon.

PMID- 21730263
TI  - The frequency of detection of unexpected diabetes mellitus during
      haemoglobinopathy investigations.
AB  - AIMS: To establish the frequency of detection of previously undiagnosed diabetes
      mellitus as a result of detection of an increased glycated fraction of
      haemoglobin during high performance liquid chromatography (HPLC) for
      haemoglobinopathy diagnosis. METHODS: A prospective study was carried out over a
      3-month period. During that period a total of 2094 patient samples were received
      for haemoglobinopathy investigation and were included in the study. RESULTS:
      Fifty samples were found to have an apparent increase in the glycated haemoglobin
      fraction and of these 38 were found to be from patients with known diabetes.
      Previously undiagnosed diabetes was discovered in 11 patients and it is likely
      that the twelfth patient also had diabetes. CONCLUSIONS: The detection of
      evidence of undiagnosed diabetes during HPLC haemoglobinopathy investigations is
      not rare, there being four cases per month in this study. This incidental
      observation should be reported to clinical staff.

PMID- 21730264
TI  - Expression and prognostic significance of survivin splice variants in diffusely
      infiltrating astrocytoma.
AB  - BACKGROUND: Alternative splicing of survivin (BIRC5) pre-mRNA generates the
      common isoform survivin and five additional splice variants: survivin2B,
      survivinDeltaEx3, survivin2alpha, survivin3B and survivin3alpha. Although the
      common isoform survivin has been shown to be involved in tumourigenesis and
      progression of various tumours, including diffusely infiltrating astrocytoma, the
      expression of other survivin splice variants in astrocytoma has not been fully
      investigated. Aims To evaluate the expression status and particularly prognostic
      significance of survivin splice variants in diffusely infiltrating astrocytoma.
      METHODS: mRNA expression of the six survivin variants in 73 diffusely
      infiltrating astrocytoma and 18 normal brain tissue samples was investigated by
      using reverse transcription-PCR (RT-PCR), and the total survivin protein
      expression by western analysis and immunohistochemistry. Association of survivin
      and its splice variants with tumour grade and prognosis was examined by
      statistical and survival analysis. RESULTS: The survivin, survivinDeltaEx3,
      survivin2B and survivin2alpha splice variants were significantly elevated in
      diffusely infiltrating astrocytoma, and were barely detectable or not detectable
      at all in normal brain tissue. Survivin3B and survivin3alpha were not detected in
      these samples. The positive rates of the expressed four variants increased with
      astrocytoma grade. Significantly, expression of these splice variants was
      associated with much poorer disease-specific and progression-free survival
      (Kaplan-Meier analysis, p<=0.002). Cox regression model further indicated
      survivin2alpha mRNA expression and nuclear survivin immunostaining to be
      significant independent negative prognostic factors. CONCLUSIONS: The survivin,
      survivinDeltaEx3, survivin2B and survivin2alpha splice variants were
      significantly elevated in astrocytoma, and were associated with tumour grade and
      poorer prognosis.

PMID- 21730265
TI  - Germ cell tumor with somatic-type malignancy presenting as right facial swelling
      in a young woman.

PMID- 21730266
TI  - Tandem autologous/reduced-intensity conditioning allogeneic stem-cell
      transplantation versus autologous transplantation in myeloma: long-term follow
      up.
AB  - PURPOSE: Results of allogeneic stem-cell transplantation (allo) in myeloma are
      controversial. In this trial autologous stem-cell transplantation (auto) followed
      by reduced-intensity conditioning matched sibling donor allo (auto-allo) was
      compared with auto only in previously untreated multiple myeloma. PATIENTS AND
      METHODS: In all, 357 patients with myeloma up to age 69 years were enrolled from
      2001 to 2005. Patients with an HLA-identical sibling donor were allocated to the
      auto-allo arm (n = 108) and patients without a matched sibling donor were
      allocated to the auto arm (n = 249). Single (n = 145) or tandem (n = 104) auto
      was optional. Conditioning for the auto arm was melphalan 200 mg/m(2);
      conditioning for the allo arm was total-body irradiation 2 Gy plus fludarabine 30
      mg/m(2)/d for 3 days. Median follow-up time was 61 months. Primary end point was
      progression-free survival. RESULTS: Progression-free survival at 60 months was
      significantly better with auto-allo than with auto [corrected] alone (35% v 18%;
      P = .001), as was the risk of death and of relapse in the long term (P = .047 and
      P = .003, respectively). Overall survival at 60 months was 65% versus 58%, and
      relapse incidence was 49% versus 78%. Complete remission rates were 51% and 41%,
      respectively (P = .020). Nonrelapse mortality at 24 months was 12% after auto
      allo compared with 3% in the auto group (P < .001). The incidence of grade 2 to 4
      acute graft-versus-host disease (GvHD) was 20%, and the incidence of limited and
      extensive chronic GvHD was 31% and 23%. CONCLUSION: In patients with previously
      untreated multiple myeloma, long-term outcome with respect to progression-free
      survival, overall survival, and relapse rate is superior after auto-allo compared
      with auto only. Nonrelapse mortality is at a reasonable level in both groups.

PMID- 21730267
TI  - Targeted therapy for human epidermal growth factor receptor 2-positive breast
      cancer: can there be too many active drugs?

PMID- 21730268
TI  - Complete remission of Waldenstrom macroglobulinemia with azacitidine and
      rituximab.

PMID- 21730269
TI  - Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of
      prognostic factors and lymph node assessment.
AB  - PURPOSE: To identify factors associated with outcome after surgical management of
      intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN)
      assessment on survival. PATIENTS AND METHODS: From an international multi
      institutional database, 449 patients who underwent surgery for ICC between 1973
      and 2010 were identified. Clinical and pathologic data were evaluated using uni-
      and multivariate analyses. RESULTS: Median tumor size was 6.5 cm. Most patients
      had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27
      months, and 5-year survival was 31%. Factors associated with adverse prognosis
      included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple
      lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor
      size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified
      using the American Joint Committee on Cancer/International Union Against Cancer
      T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P
      < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%)
      had LN metastasis. LN metastasis was associated with worse outcome (median
      survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN
      metastasis were able to be stratified by tumor number and vascular invasion (N0;
      P < .001), among patients with N1 disease, multiple tumors and vascular invasion,
      either alone or together, failed to discriminate patients into discrete
      prognostic groups (P = .34). CONCLUSION: Although tumor size provides no
      prognostic information, tumor number, vascular invasion, and LN metastasis were
      associated with survival. N1 status adversely affected overall survival and also
      influenced the relative effect of tumor number and vascular invasion on
      prognosis. Lymphadenectomy should be strongly considered for ICC, because up to
      30% of patients will have LN metastasis.

PMID- 21730270
TI  - Heterogeneous distribution of EGFR mutations is extremely rare in lung
      adenocarcinoma.
AB  - PURPOSE: Some studies have shown that epidermal growth factor receptor (EGFR)
      mutations can be heterogeneously distributed in individual tumors. In this study,
      we re-evaluated the distribution of EGFR mutations within tumors. PATIENTS AND
      METHODS: We used multiple approaches, including an analysis of simultaneous dual
      hot spot mutations, a trans-sectional analysis of individual lung
      adenocarcinomas, and comparisons of the mutation patterns between primary and
      metastatic sites and between primary and recurrent tumors. RESULTS: None of the
      862 tumors harboring an EGFR mutation showed simultaneous dual hot spot
      mutations, although identical EGFR mutations were found throughout individual
      tumors in a trans-sectional analysis involving 50 tumors divided into three parts
      and five lung adenocarcinomas divided into 100 parts. In addition, no discordant
      mutation patterns were detected among 77 paired primary and metastatic site
      samples or among 54 primary and recurrent tumor pairs. CONCLUSION: All of these
      results suggest that the heterogeneous distribution of EGFR mutations is
      extremely rare. However, it is possible that pseudoheterogeneity occurs because
      of a combination of mutant allele-specific imbalance and heterogeneously
      distributed EGFR amplification, especially when a less sensitive method is used
      for detection. Specifically, when EGFR amplification occurs, the mutant allele is
      amplified, and this amplification is involved in invasive growth. Accordingly,
      invasive growth area significantly over-represents the mutation signal. In
      contrast, weak EGFR mutation signals in the area without EGFR amplification may
      not reach the threshold of detection because of the mixture with normal cells.
      Such unbalanced mutation signals might lead to pseudoheterogeneity.

PMID- 21730271
TI  - Mantle cell lymphoma international prognostic index but not pretransplantation
      induction regimen predicts survival for patients with mantle-cell lymphoma
      receiving high-dose therapy and autologous stem-cell transplantation.
AB  - PURPOSE: High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT)
      are frequently used in an attempt to improve outcome in patients with mantle-cell
      lymphoma (MCL); however, the importance of intensive induction regimens before
      transplantation is unknown. PATIENTS AND METHODS: To address this question, we
      evaluated baseline characteristics, time to treatment, induction regimen, disease
      status at the time of transplantation, and MIPI score at diagnosis and their
      associations with survival in 118 consecutive patients with MCL who received HDT
      and ASCT at our centers. RESULTS: The MIPI was independently associated with
      survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P <
      .001) and in the 85 patients who underwent ASCT as initial consolidation (HR,
      7.2; P < .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from
      ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively.
      Low-risk MIPI scores were more common in the intensive induction group than the
      standard induction group in all patients (64% v 46%, respectively; P = .03) and
      in the initial consolidation group (66% v 45%, respectively; P = .03). After
      adjustment for the MIPI, an intensive induction regimen was not associated with
      improved survival after transplantation in all patients (HR, 0.5; P = .10), the
      initial consolidation group (HR, 1.1; P = .86), or patients <= 60 years old (HR,
      0.6; P = .50). Observation of more than 3 months before initiating therapy did
      not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in
      patients receiving ASCT. CONCLUSION: An intensive induction regimen before HDT
      and ASCT was not associated with improved survival after adjusting for
      differences in MIPI scores at diagnosis.

PMID- 21730272
TI  - Severe docetaxel overdose induced by pharmacokinetic interaction with
      dronedarone.

PMID- 21730273
TI  - Variability of lung tumor measurements on repeat computed tomography scans taken
      within 15 minutes.
AB  - PURPOSE: We use changes in tumor measurements to assess response and progression,
      both in routine care and as the primary objective of clinical trials. However,
      the variability of computed tomography (CT) -based tumor measurement has not been
      comprehensively evaluated. In this study, we assess the variability of lung tumor
      measurement using repeat CT scans performed within 15 minutes of each other and
      discuss the implications of this variability in a clinical context. PATIENTS AND
      METHODS: Patients with non-small-cell lung cancer and a target lung lesion >= 1
      cm consented to undergo two CT scans within a period of minutes. Three
      experienced radiologists measured the diameter of the target lesion on the two
      scans in a side-by-side fashion, and differences were compared. RESULTS: Fifty
      seven percent of changes exceeded 1 mm in magnitude, and 33% of changes exceeded
      2 mm. Median increase and decrease in tumor measurements were +4.3% and -4.2%,
      respectively, and ranged from 23% shrinkage to 31% growth. Measurement changes
      were within +/- 10% for 84% of measurements, whereas 3% met criteria for
      progression according to Response Evaluation Criteria in Solid Tumors (RECIST; >=
      20% increase). Smaller lesions had greater variability of percent measurement
      change (P = .005). CONCLUSION: Apparent changes in tumor diameter exceeding 1 to
      2 mm are common on immediate reimaging. Increases and decreases less than 10% can
      be a result of the inherent variability of reimaging. Caution should be exercised
      in interpreting the significance of small changes in lesion size in the care of
      individual patients and in the interpretation of clinical trial results.

PMID- 21730274
TI  - A time to keep and a time to cast away categories of tumor response.

PMID- 21730275
TI  - Phase I/II study of trastuzumab in combination with everolimus (RAD001) in
      patients with HER2-overexpressing metastatic breast cancer who progressed on
      trastuzumab-based therapy.
AB  - PURPOSE: Trastuzumab resistance has been linked to activation of the
      phosphoinositol 3-kinase (PI3K) pathway. Phosphatase and tensin homolog (PTEN) is
      a dual phosphatase that counteracts the PI3K function; PTEN loss leads to
      activation of the Akt cascade and the downstream mammalian target of rapamycin
      (mTOR). Preclinical studies demonstrated that mTOR inhibition sensitized the
      response to trastuzumab in mice with HER2 overexpressing and PTEN-deficient
      breast xenografts. Our trial evaluated the safety and efficacy of the combination
      of everolimus and trastuzumab in women with HER2-overexpressing metastatic breast
      cancer (MBC) that progressed on trastuzumab-based therapy. PATIENTS AND METHODS:
      This represents a pooled analysis (n = 47), stemming from two trials that
      occurred concurrently in The University of Texas MD Anderson Cancer Center, Beth
      Israel Deaconess Medical Center, and Dana-Farber Cancer Institute. Patients with
      HER2-overexpressing MBC who had progressed on trastuzumab-based therapy received
      trastuzumab every 3 weeks in combination with daily everolimus. RESULTS: Among 47
      patients, the combination of everolimus and trastuzumab provided partial
      responses in seven patients (15%) and persistent stable disease (lasting 6 months
      or longer) in nine patients (19%), resulting in a clinical benefit rate of 34%.
      The median progression-free survival (PFS) was 4.1 month. Fatigue, infection, and
      mucositis were the predominant nonhematologic toxicities. Trastuzumab did not
      have significant influence on the pharmacokinetic profile of everolimus. Patients
      with PTEN loss demonstrated decreased overall survival (P = .048). However, PFS
      was not affected by PTEN loss. CONCLUSION: Inhibition of mTOR results in clinical
      benefit and disease response in patients with trastuzumab-resistant HER2
      overexpressing MBC.

PMID- 21730276
TI  - Prothrombin complex concentrate for critical bleeding.
AB  - OBJECTIVE: To review the evidence supporting the use of prothrombin complex
      concentrate (PCC) as a hemostatic agent in individuals without hemophilia. DATA
      SOURCES: Articles were identified through a search of Ovid/MEDLINE (up to April
      2011) and Cochrane Central Register of Controlled Trials (up to April 2011). The
      search terms used were prothrombin complex concentrate, hemorrhage, and bleeding.
      STUDY SELECTION AND DATA EXTRACTION: The search was limited to comparative
      studies. Bibliographies of retrieved articles were reviewed to obtain additional
      articles. The intent of the search was to identify original research comparing
      PCC to fresh frozen plasma (FFP) or recombinant factor VIIa for the management of
      bleeding in patients without hemophilia. DATA SYNTHESIS: PCCs are recommended as
      an alternative to FFP and recombinant factor VIIa for the treatment of serious or
      life-threatening bleeding related to vitamin K antagonist therapy. Studies in
      this setting have shown that PCCs are safe and effective and provide prompt
      reduction of international normalized ratio (INR) compared to FFP. However, most
      trials are uncontrolled, and the primary outcomes in these studies have been INR
      reduction rather than hemostatic effect. Other common off-label uses include
      coagulopathy due to hepatic failure and traumatic hemorrhage; however, there is
      insufficient evidence to support use of PCC in these settings. Advantages of PCC
      include the low drug volume required compared to FFP. The use of PCC may be
      associated with thromboembolic complications. CONCLUSIONS: PCC is a safe and
      effective alternative to FFP and provides rapid reversal of INR in patients on
      vitamin K antagonist therapy. These agents may be advantageous compared to FFP in
      patients with volume restrictions. Comparative trials are needed to compare the
      various PCC products, FPP, and recombinant factor VIIa with regard to clinically
      significant outcomes such as hemostatic effect.

PMID- 21730278
TI  - Efficacy and safety of long-acting glucagon-like peptide-1 receptor agonists
      compared with exenatide twice daily and sitagliptin in type 2 diabetes mellitus:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Long-acting glucagon-like peptide-1 receptor agonists (LA-GLP-1RAs)
      may deliver additional therapeutic benefits over other available incretin-based
      therapies. OBJECTIVE: To pool results of randomized controlled trials comparing
      the efficacy and safety of maximum dose LA-GLP-1RAs (liraglutide, exenatide once
      weekly) with exenatide twice daily and dipeptidyl-peptidase-IV inhibitors in
      patients with type 2 diabetes. METHODS: We searched PubMed, Cochrane Central
      Register of Controlled Trials and Database of Systematic Reviews, EMBASE (all
      from inception-December 2010), and abstracts presented at the American Diabetes
      Association Scientific Sessions in 2009 and 2010 to identify English-language
      reports of studies of at least 24 weeks' duration. The primary endpoint was mean
      change in hemoglobin A(1c) (A1C) from baseline to study endpoint. Weighted mean
      differences or odds ratios and their 95% confidence intervals for each outcome
      relative to control were calculated as appropriate. RESULTS: A1C was reduced
      favoring LA-GLP-1RAs compared with exenatide twice daily and sitagliptin
      (weighted mean difference [WMD] -0.47% [95% CI -0.69 to -0.25] and WMD -0.60%
      [95% CI -0.75 to -0.45], respectively). Odds ratios greater than 1 favored LA-GLP
      1RAs for reaching the A1C target goal of less than 7%. Fasting plasma glucose
      (FPG) was reduced and favored the LA-GLP-1RA-based regimens. Exenatide
      demonstrated significantly greater reductions in postprandial glucose (PPG) after
      the morning and evening meals, compared with LA-GLP-1RAs. Body weight was reduced
      similarly between LA-GLP-1RAs and exenatide, but favored LA-GLP-1RAs in the
      sitagliptin comparator trials. LA-GLP-1RA therapy was not associated with severe
      hypoglycemia or acute pancreatitis. Compared with exenatide twice daily, vomiting
      was reduced significantly with LA-GLP-1RAs (OR 0.55; 95% CI 0.34 to 0.89); there
      was a trend toward decreased nausea (OR 0.58; 95% CI 0.32 to 1.06) and no
      difference in the incidence of diarrhea (OR 1.03; 95% CI 0.67 to 1.58).
      CONCLUSIONS: Compared with other incretin-based therapies, LA-GLP-1RAs produce
      greater improvement in A1C and FPG. They provide lesser effect on PPG, similar
      reduction in body weight, and result in a potentially favorable adverse event
      profile compared with exenatide twice daily.

PMID- 21730279
TI  - Tigecycline for the treatment of severe Clostridium difficile infection.
AB  - OBJECTIVE: To evaluate the evidence for the use of tigecycline in the treatment
      of Clostridium difficile infection (CDI). DATA SOURCES: Searches were performed
      (2004 to June 2011), using the EMBASE and MEDLINE databases, with the terms
      tigecycline, Tygacil, Clostridium difficile, C. difficile, Clostridium difficile
      infection, and CDI. STUDY SELECTION: Six case reports that described the use of
      tigecycline for treatment of CDI were included for review. No clinical trials
      were identified. DATA SYNTHESIS: In all case reports except 1, tigecycline (alone
      or in combination with other CDI therapies) was used for the treatment of CDI
      that was refractory to metronidazole and/or vancomycin. In 6 of the cases,
      treatment success was reported following initiation of tigecycline therapy; 1
      patient died following a complicated hospitalization. The treatment duration with
      tigecycline was 2-4 weeks. In the cases with successful outcomes, symptoms began
      to improve within 1 week. None of these patients experienced recurrence during
      follow-up of various lengths. In vitro studies demonstrated a 90% minimum
      inhibitory concentration range for tigecycline of 0.016-0.25 mg/L for all C.
      difficile isolates. Tigecycline exhibited good fecal penetration because of
      primary biliary excretion of unchanged drug. Up to 59% of the dose is recovered
      in feces following administration over 4 days in healthy volunteers. CONCLUSIONS:
      Case reports have suggested that tigecycline may be successful for treatment of
      severe or severe complicated CDI, when prior therapy has failed. Data
      demonstrating tigecycline use as initial therapy for CDI are limited; therefore,
      this option should be reserved for patients in whom other therapeutic options,
      including metronidazole and vancomycin, have failed. A randomized controlled
      trial is needed to assess the safety and efficacy of tigecycline in this patient
      population and better define the drug's role in the treatment of CDI.

PMID- 21730280
TI  - Influence of intravenous opioid dose on postoperative ileus.
AB  - BACKGROUND: Intravenous opioids represent a major component in the
      pathophysiology of postoperative ileus (POI). However, the most appropriate
      measure and threshold to quantify the association between opioid dose (eg,
      average daily, cumulative, maximum daily) and POI remains unknown. OBJECTIVE: To
      evaluate the relationship between opioid dose, POI, and length of stay (LOS) and
      identify the opioid measure that was most strongly associated with POI. METHODS:
      Consecutive patients admitted to a community teaching hospital who underwent
      elective colorectal surgery by any technique with an enhanced-recovery protocol
      postoperatively were retrospectively identified. Patients were excluded if they
      received epidural analgesia, developed a major intraabdominal complication or
      medical complication, or had a prolonged workup prior to surgery. Intravenous
      opioid doses were quantified and converted to hydromorphone equivalents.
      Classification and regression tree (CART) analysis was used to determine the
      dosing threshold for the opioid measure most associated with POI and define high
      versus low use of opioids. Risk factors for POI and prolonged LOS were determined
      through multivariate analysis. RESULTS: The incidence of POI in 279 patients was
      8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of
      2 mg or more as the opioid measure most associated with POI. Multivariate
      analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034),
      open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p
      = 0.003) as significant risk factors for POI. Variables associated with increased
      LOS were POI (p < 0.001), maximum daily hydromorphone dose of 2 mg or more (p <
      0.001), and age (p = 0.005); laparoscopy (p < 0.001) was associated with a
      decreased LOS. CONCLUSIONS: Intravenous opioid therapy is significantly
      associated with POI and prolonged LOS, particularly when the maximum
      hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative,
      nonopioid-based pain management options when this occurs.

PMID- 21730282
TI  - Busulfan and metronidazole: an often forgotten but significant drug interaction.
AB  - OBJECTIVE: To report the case of a clinically significant drug interaction
      between intravenous busulfan and oral metronidazole observed through busulfan
      therapeutic drug monitoring (TDM). CASE SUMMARY: A 7-year-old boy with a history
      of myelodysplasia that progressed to acute myeloid leukemia received busulfan
      with therapeutic drug monitoring (TDM), clofarabine, and thiotepa as a
      pretransplant conditioning regimen for a cord blood transplant. The patient
      received metronidazole the day after a busulfan test dose of 0.5 mg/kg was
      administered. On the day of the first busulfan therapeutic dose, TDM was
      performed and the clearance of busulfan was significantly decreased by 46%. After
      2 doses of busulfan therapy, the course area under the curve was exceeded,
      requiring discontinuation of busulfan. Metronidazole is not known to affect
      glutathione or the glutathione S-transferase A1 (GSTA1) enzyme system or
      cytochrome P450 (CYP) 3A4. DISCUSSION: Busulfan is a bifunctional alkylating
      agent widely used in pretransplant conditioning regimens in patients undergoing
      stem cell transplantation for hematologic malignancies. Busulfan metabolism is
      best described by hepatic conjugation to glutathione by GSTA1, although some CYP
      dependent pathways have been described. Currently there is 1 publication
      describing the drug interaction between oral busulfan and oral metronidazole, in
      which concomitant use of metronidazole resulted in higher busulfan trough
      concentrations and higher risk of veno-occlusive disease. Our case represents a
      possible drug interaction based on the Horn Drug Interaction Probability Scale.
      CONCLUSIONS: Though the mechanistic basis for this interaction is unknown, the
      risks and benefits of using metronidazole during and in close proximity to
      busulfan should be carefully considered and therapeutic alternatives to
      metronidazole should be used when appropriate.

PMID- 21730283
TI  - Metabolic syndrome and erectile dysfunction: the ultrasound evaluation of
      cavernosal atherosclerosis.
AB  - OBJECTIVE: To study the relation between metabolic syndrome (MS), cavernosal
      morphological vasculopathy, and peripheral vascular alterations (carotid and
      femoral wall) in patients with erectile dysfunction. RESEARCH DESIGN AND METHODS:
      A total of 207 patients and 50 control subjects were evaluated for cardiovascular
      risk factors, physical examination, reproductive hormones, ultrasound analysis of
      cavernosal, carotid and femoral arteries (intima-media thickness), and cavernosal
      flow measurement (peak systolic velocity). RESULTS: A total of 28% of patients
      had MS, and they presented with a high prevalence of cavernosal alterations
      (70.3%) and systemic vascular impairment (59.3%), whereas patients with
      cavernosal alterations (44%) showed the higher prevalence of MS (48.9%). The
      number of MS components was related to the prevalence of penile vasculopathy.
      However, multivariate analysis showed that MS is not an independent predictor for
      cavernosal vasculopathy. CONCLUSIONS: Patients with cavernosal vasculopathy have
      an increased cardiometabolic risk, and screening for MS components might identify
      individuals with a higher risk for cavernosal and systemic atherosclerosis.

PMID- 21730284
TI  - The triglyceride-to-HDL cholesterol ratio: association with insulin resistance in
      obese youths of different ethnic backgrounds.
AB  - OBJECTIVE: We evaluated whether the triglyceride-to-HDL cholesterol (TG/HDL-C)
      ratio is associated with insulin resistance (IR) in a large multiethnic cohort of
      obese youths. RESEARCH DESIGN AND METHODS: Obese youths (1,452) had an oral
      glucose tolerance test and a fasting lipid profile. Insulin sensitivity was
      estimated using the whole body insulin sensitivity index (WBISI) and homeostasis
      model assessment (HOMA)-IR and evaluated, in a subgroup of 146 obese youths, by
      the hyperinsulinemic-euglycemic clamp. The cohort was divided by ethnicity (612
      whites, 357 Hispanics, and 483 African Americans) and then stratified into
      ethnicity-specific tertiles of TG/HDL-C ratio. Differences across tertiles were
      evaluated, and the association between the TG/HDL-C ratio and insulin sensitivity
      (WBISI) was defined by a multiple stepwise linear regression analysis. The area
      under the receiver operating characteristic (ROC) curve (AUC) was determined to
      calculate the TG/HDL-C ratio cutoff to identify insulin-resistant subjects by
      ethnicity. RESULTS: In each ethnic group and across rising tertiles of TG/HDL-C
      ratio, insulin sensitivity (WBISI) progressively decreased, whereas 2-h glucose
      and the AUC-glucose progressively increased. The cutoff for TG/HDL-C ratio was
      2.27, and the odds of presenting with IR, in youths with TG/HDL-C ratio higher
      than the cutoff, was 6.023 (95% CI 2.798-12.964; P < 0.001) in white girls and
      boys, whereas for both Hispanics and African Americans the AUC-ROCs were not
      significant, thus not allowing the calculation of an optimal cutoff TG/HDL-C
      value. CONCLUSIONS: The TG/HDL-C ratio is associated with IR mainly in white
      obese boys and girls and thus may be used with other risk factors to identify
      subjects at increased risk of IR-driven morbidity.

PMID- 21730285
TI  - Nuclear extracellular signal-regulated kinase 1 and 2 translocation is mediated
      by casein kinase 2 and accelerated by autophosphorylation.
AB  - The extracellular signal-regulated kinases (ERK) 1 and 2 (ERK1/2) are members of
      the mitogen-activated protein kinase [MAPK] family. Upon stimulation, these
      kinases translocate from the cytoplasm to the nucleus, where they induce
      physiological processes such as proliferation and differentiation. The mechanism
      of translocation of this kinase involves phosphorylation of two Ser residues
      within a nuclear translocation signal (NTS), which allows binding to importin7
      and a subsequent penetration via nuclear pores. Here we show that the
      phosphorylation of both Ser residues is mediated mainly by casein kinase 2 (CK2)
      and that active ERK may assist in the phosphorylation of the N-terminal Ser. We
      also demonstrate that the phosphorylation is dependent on the release of ERK from
      cytoplasmic anchoring proteins. Crystal structure of the phosphomimetic ERK
      revealed that the NTS phosphorylation creates an acidic patch in ERK. Our model
      is that in resting cells ERK is bound to cytoplasmic anchors, which prevent its
      NTS phosphorylation. Upon stimulation, phosphorylation of the ERK TEY domain
      releases ERK and allows phosphorylation of its NTS by CK2 and active ERK to
      generate a negatively charged patch in ERK, binding to importin 7 and nuclear
      translocation. These results provide an important role of CK2 in regulating
      nuclear ERK activities.

PMID- 21730286
TI  - MicroRNA-146a inhibits glioma development by targeting Notch1.
AB  - Dysregulated epidermal growth factor receptor (EGFR) signaling through either
      genomic amplification or dominant-active mutation (EGFR(vIII)), in combination
      with the dual inactivation of INK4A/ARF and PTEN, is a leading cause of
      gliomagenesis. Our global expression analysis for microRNAs revealed that EGFR
      activation induces miR-146a expression, which is further potentiated by
      inactivation of PTEN. Unexpectedly, overexpression of miR-146a attenuates the
      proliferation, migration, and tumorigenic potential of Ink4a/Arf(-/-) Pten(-/-)
      Egfr(vIII) murine astrocytes. Its ectopic expression also inhibits the glioma
      development of a human glioblastoma cell line in an orthotopic xenograft model.
      Such an inhibitory function of miR-146a on gliomas is largely through
      downregulation of Notch1, which plays a key role in neural stem cell maintenance
      and is a direct target of miR-146a. Accordingly, miR-146a modulates neural stem
      cell proliferation and differentiation and reduces the formation and migration of
      glioma stem-like cells. Conversely, knockdown of miR-146a by microRNA sponge
      upregulates Notch1 and promotes tumorigenesis of malignant astrocytes. These
      findings indicate that, in response to oncogenic cues, miR-146a is induced as a
      negative-feedback mechanism to restrict tumor growth by repressing Notch1. Our
      results provide novel insights into the signaling pathways that link neural stem
      cells to gliomagenesis and may lead to new strategies for treating brain tumors.

PMID- 21730287
TI  - Inhibition of nonsense-mediated RNA decay by the tumor microenvironment promotes
      tumorigenesis.
AB  - While nonsense-mediated RNA decay (NMD) is an established mechanism to rapidly
      degrade select transcripts, the physiological regulation and biological
      significance of NMD are not well characterized. We previously demonstrated that
      NMD is inhibited in hypoxic cells. Here we show that the phosphorylation of the
      alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) translation
      initiation factor by a variety of cellular stresses leads to the inhibition of
      NMD and that eIF2alpha phosphorylation and NMD inhibition occur in tumors. To
      explore the significance of this NMD regulation, we used an unbiased approach to
      identify approximately 750 NMD-targeted mRNAs and found that these mRNAs are
      overrepresented in stress response and tumor-promoting pathways. Consistent with
      these findings, the inhibition of NMD promotes cellular resistance to endoplasmic
      reticulum stress and encourages tumor formation. The transcriptional and
      translational regulations of gene expression by the microenvironment are
      established mechanisms by which tumor cells adapt to stress. These data indicate
      that NMD inhibition by the tumor microenvironment is also an important mechanism
      to dynamically regulate genes critical for the response to cellular stress and
      tumorigenesis.

PMID- 21730288
TI  - Slowly progressing nucleotide excision repair in trichothiodystrophy group A
      patient fibroblasts.
AB  - Trichothiodystrophy (TTD) is a rare autosomal premature-ageing and
      neuroectodermal disease. The photohypersensitive form of TTD is caused by
      inherited mutations in three of the 10 subunits of the basal transcription factor
      TFIIH. TFIIH is an essential transcription initiation factor that is also pivotal
      for nucleotide excision repair (NER). Photosensitive TTD is explained by
      deficient NER, dedicated to removing UV-induced DNA lesions. TTD group A (TTD-A)
      patients carry mutations in the smallest TFIIH subunit, TTDA, which is an 8-kDa
      protein that dynamically interacts with TFIIH. TTD-A patients display a
      relatively mild TTD phenotype, and TTD-A primary fibroblasts exhibit moderate UV
      sensitivity despite a rather low level of UV-induced unscheduled DNA synthesis
      (UDS). To investigate the rationale of this seeming discrepancy, we studied the
      repair kinetics and the binding kinetics of TFIIH downstream NER factors to
      damaged sites in TTD-A cells. Our results show that TTD-A cells do repair UV
      lesions, although with reduced efficiency, and that the binding of downstream NER
      factors on damaged DNA is not completely abolished but only retarded. We conclude
      that in TTD-A cells repair is not fully compromised but only delayed, and we
      present a model that explains the relatively mild photosensitive phenotype
      observed in TTD-A patients.

PMID- 21730289
TI  - Regulation of androgen receptor-mediated transcription by RPB5 binding protein
      URI/RMP.
AB  - Androgen receptor (AR)-mediated transcription is modulated by interaction with
      coregulatory proteins. We demonstrate that the unconventional prefoldin RPB5
      interactor (URI) is a new regulator of AR transcription and is critical for
      antagonist (bicalutamide) action. URI is phosphorylated upon androgen treatment,
      suggesting communication between the URI and AR signaling pathways. Whereas
      depletion of URI enhances AR-mediated gene transcription, overexpression of URI
      suppresses AR transcriptional activation and anchorage-independent prostate
      cancer cell growth. Repression of AR-mediated transcription is achieved, in part,
      by URI binding and regulation of androgen receptor trapped clone 27 (Art-27), a
      previously characterized AR corepressor. Consistent with this idea, genome-wide
      expression profiling in prostate cancer cells upon depletion of URI or Art-27
      reveals substantially overlapping patterns of gene expression. Further, depletion
      of URI increases the expression of the AR target gene NKX-3.1, decreases the
      recruitment of Art-27, and increases AR occupancy at the NKX-3.1 promoter. While
      Art-27 can bind AR directly, URI is bound to chromatin prior to hormone-dependent
      recruitment of AR, suggesting a role for URI in modulating AR recruitment to
      target genes.

PMID- 21730291
TI  - MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis.
AB  - MICALs (molecules interacting with CasL) are atypical multidomain flavoenzymes
      with diverse cellular functions. The molecular pathways employed by MICAL
      proteins to exert their cellular effects remain largely uncharacterized. Via an
      unbiased proteomics approach, we identify MICAL-1 as a binding partner of NDR
      (nuclear Dbf2-related) kinases. NDR1/2 kinases are known to mediate apoptosis
      downstream of the mammalian Ste-20-like kinase MST1, and ablation of NDR1 in mice
      predisposes the mice to cancer as a result of compromised apoptosis. MST1
      phosphorylates NDR1/2 kinases at their hydrophobic motif, thereby facilitating
      full NDR kinase activity and function. However, if and how this key
      phosphorylation event is regulated are unknown. Here we show that MICAL-1
      interacts with the hydrophobic motif of NDR1/2 and that overexpression or
      knockdown of MICAL-1 reduces or augments NDR kinase activation or activity,
      respectively. Surprisingly, MICAL-1 is a phosphoprotein but not an NDR or MST1
      substrate. Rather, MICAL-1 competes with MST1 for NDR binding and thereby
      antagonizes MST1-induced NDR activation. In line with this inhibitory effect,
      overexpression or knockdown of MICAL-1 inhibits or enhances, respectively, NDR
      dependent proapoptotic signaling induced by extrinsic stimuli. Our findings
      unveil a previously unknown biological role for MICAL-1 in apoptosis and define a
      novel negative regulatory mechanism of MST-NDR signaling.

PMID- 21730290
TI  - Identification of histone mutants that are defective for transcription-coupled
      nucleosome occupancy.
AB  - Our previous studies of Saccharomyces cerevisiae described a gene repression
      mechanism where the transcription of intergenic noncoding DNA (ncDNA) (SRG1)
      assembles nucleosomes across the promoter of the adjacent SER3 gene that
      interfere with the binding of transcription factors. To investigate the role of
      histones in this mechanism, we screened a comprehensive library of histone H3 and
      H4 mutants for those that derepress SER3. We identified mutations altering eight
      histone residues (H3 residues V46, R49, V117, Q120, and K122 and H4 residues R36,
      I46, and S47) that strongly increase SER3 expression without reducing the
      transcription of the intergenic SRG1 ncDNA. We detected reduced nucleosome
      occupancy across SRG1 in these mutants to degrees that correlate well with the
      level of SER3 derepression. The histone chromatin immunoprecipitation experiments
      on several other genes suggest that the loss of nucleosomes in these mutants is
      specific to highly transcribed regions. Interestingly, two of these histone
      mutants, H3 R49A and H3 V46A, reduce Set2-dependent methylation of lysine 36 of
      histone H3 and allow transcription initiation from cryptic intragenic promoters.
      Taken together, our data identify a new class of histone mutants that is
      defective for transcription-dependent nucleosome occupancy.

PMID- 21730292
TI  - Hypoxia leads to Na,K-ATPase downregulation via Ca(2+) release-activated Ca(2+)
      channels and AMPK activation.
AB  - To maintain cellular ATP levels, hypoxia leads to Na,K-ATPase inhibition in a
      process dependent on reactive oxygen species (ROS) and the activation of AMP
      activated kinase alpha1 (AMPK-alpha1). We report here that during hypoxia AMPK
      activation does not require the liver kinase B1 (LKB1) but requires the release
      of Ca(2+) from the endoplasmic reticulum (ER) and redistribution of STIM1 to ER
      plasma membrane junctions, leading to calcium entry via Ca(2+) release-activated
      Ca(2+) (CRAC) channels. This increase in intracellular Ca(2+) induces
      Ca(2+)/calmodulin-dependent kinase kinase beta (CaMKKbeta)-mediated AMPK
      activation and Na,K-ATPase downregulation. Also, in cells unable to generate
      mitochondrial ROS, hypoxia failed to increase intracellular Ca(2+) concentration
      while a STIM1 mutant rescued the AMPK activation, suggesting that ROS act
      upstream of Ca(2+) signaling. Furthermore, inhibition of CRAC channel function in
      rat lungs prevented the impairment of alveolar fluid reabsorption caused by
      hypoxia. These data suggest that during hypoxia, calcium entry via CRAC channels
      leads to AMPK activation, Na,K-ATPase downregulation, and alveolar epithelial
      dysfunction.

PMID- 21730293
TI  - The socioeconomics of hypertension: how $50 000 may buy a drop in blood pressure.

PMID- 21730294
TI  - Role of vascular extracellular superoxide dismutase in hypertension.
AB  - Previous studies indicate that superoxide is important in the modulation of blood
      pressure but have not specifically identified the cell types or organs involved.
      We created mice with loxP sites flanking the extracellular superoxide dismutase
      (SOD3) gene. These mice were crossed with mice expressing inducible Cre
      recombinase driven by the smooth muscle myosin heavy chain promoter allowing
      tissue-specific deletion of SOD3. Deletion of SOD3 increased vascular superoxide
      and reduced vascular NO levels as detected by electron spin resonance. Despite
      these changes in NO and superoxide, we did not observe increases in vascular
      inflammation caused by angiotensin II. Moreover, deletion of vascular SOD3 did
      not augment hypertension in response to angiotensin II. In additional studies, we
      also deleted SOD3 from the circumventricular organs by intracerebroventricular
      injection of an adenovirus encoding Cre-recombinase. Although this raised blood
      pressure and augmented the hypertension caused by angiotensin II, these responses
      were not further increased by vascular deletion of SOD3. These data suggest that
      the extracellular superoxide dismutase in vascular smooth muscle is not involved
      in the genesis of angiotensin II-induced hypertension and further emphasize the
      role of central SOD3 in the modulation of blood pressure.

PMID- 21730295
TI  - Mast cells and cardiac fibroblasts: accomplices in elevation of collagen
      synthesis in modulation of fibroblast phenotype.

PMID- 21730296
TI  - Systolic blood pressure, socioeconomic status, and biobehavioral risk factors in
      a nationally representative US young adult sample.
AB  - In the National Longitudinal Study of Adolescent Health, a US longitudinal study
      of >15 000 young adults, we examined the extent to which socioeconomic status is
      linked to systolic blood pressure (SBP) and whether biobehavioral risk factors
      mediate the association. More than 62% of the participants had SBP >120 mm Hg and
      12% had SBP >140 mm Hg. More than 66% were classified as at least overweight
      (body mass index >25 kg/m(2)), with >36% meeting criteria for at least class I
      obesity (body mass index >30 kg/m(2)). Multivariate models showed that higher
      household income and being married were independently associated with lower SBP.
      Higher body mass index, greater waist circumference, smoking, and higher alcohol
      intake were each independently associated with higher SBP. Meditational analyses
      suggested that higher education level was associated with lower SBP by way of
      lower body mass, smaller waist circumference, and lower resting heart rate. When
      these indirect effects were accounted for, education was not significantly
      associated with SBP. In contrast, household income remained associated with SBP
      even with control for all of the covariates. Results reinforce current public
      health concerns about rates of obesity and high blood pressure among young adults
      and suggest that disparities in education level and household income may play an
      important role in the observed decrements in health. Identifying modifiable
      mechanisms that link socioeconomic status to SBP using data from a large
      representative sample may improve risk stratification and guide the development
      of effective interventions.

PMID- 21730297
TI  - Tryptase/Protease-activated receptor 2 interactions induce selective mitogen
      activated protein kinase signaling and collagen synthesis by cardiac fibroblasts.
AB  - The mast cell product, tryptase, has recently been implicated to mediate fibrosis
      in the hypertensive heart. Tryptase has been shown to mediate noncardiac
      fibroblast function via activation of protease-activated receptor 2 and
      subsequent activation of the mitogen-activated protein kinase pathway, including
      extracellular signal-regulated kinase 1/2. Therefore, we hypothesized that this
      pathway may be a mechanism leading to fibrosis in the hypertensive heart.
      Isolated adult cardiac fibroblasts were treated with tryptase, which induced
      activation of extracellular signal-regulated kinase 1/2 via protease-activated
      receptor 2. Blockade of protease activated receptor 2 with FSLLRY (10 MUmol/L)
      and inhibition of the extracellular signal-regulated kinase pathway with PD98059
      (10 MUmol/L) prevented collagen synthesis in isolated cardiac fibroblasts
      stimulated with tryptase. In contrast, p38 mitogen-activated protein kinase and
      stress-activated protein/c-Jun N-terminal kinase were not activated by tryptase.
      Cardiac fibroblasts isolated from spontaneously hypertensive rats showed this
      same pattern of activation. Treatment of spontaneously hypertensive rats with
      FSLLRY prevented fibrosis in these animals, indicating the in vivo applicability
      of the cultured fibroblast findings. Also, tryptase induced a myofibroblastic
      phenotype indicated by elevations in alpha-smooth muscle actin and extra type III
      domain A (ED-A) fibronectin. Thus, the results from this study demonstrate the
      importance of tryptase for inducing a cardiac myofibroblastic phenotype,
      ultimately leading to the development of cardiac fibrosis. Specifically, tryptase
      causes cardiac fibroblasts to increase collagen synthesis via a mechanism
      involving activation of protease-activated receptor 2 and subsequent induction of
      extracellular signal-regulated kinase signaling.

PMID- 21730298
TI  - Novel expression and regulation of voltage-dependent potassium channels in
      placentas from women with preeclampsia.
AB  - Preeclampsia is associated with structural/functional alterations in placental
      and maternal vasculature. Voltage-dependant potassium channels encoded by KCNQ1-5
      genes have been detected in several types of blood vessels where they promote
      vascular relaxation. Voltage-dependant potassium channel function can be
      modulated by KCNE1-5-encoded accessory proteins. The aim of this study was to
      determine whether KCNQ and KCNE genes are differentially expressed in placentas
      from women with preeclampsia compared with normotensive controls and to examine
      any differences in those who delivered preterm (<37 weeks) or term. Placental
      biopsies (from midway between the cord and periphery) were obtained, with
      consent, from white European control (n=24; term) and preeclamptic (n=22; of whom
      8 delivered before 37 weeks' gestation) women. KCNQ/KCNE and GAPDH mRNA
      expressions were determined by quantitative RT-PCR. Protein
      expression/localization was assessed using immunohistochemistry. KCNQ3 and KCNE5
      mRNA expressions were significantly upregulated in preeclampsia (median
      [interquartile range]: 1.942 [0.905 to 3.379]) versus controls (0.159 [0.088 to
      0.288]; P=0.001) and exhibited a strong positive correlation with each other
      (P<0.001), suggesting a novel heterodimer. Enhanced protein expression of KCNQ3
      and KCNE5 in preeclampsia was confirmed with localization mainly restricted to
      the syncytiotrophoblast. KCNQ4 and KCNE1 isoforms were suppressed in placentas
      from term preeclamptic women versus controls (P<=0.05). KCNQ1 mRNA expression was
      increased and KCNQ5 decreased in the preterm preeclamptic group versus controls
      (P<0.05). In summary, voltage-dependant potassium channels are expressed and
      markedly modulated in placentas from preeclamptic women. Differential expression
      of isoforms may lead to altered cell proliferation. The correlation between KCNQ3
      and KCNE5 expression is indicative of a novel channel complex and warrants
      further investigation.

PMID- 21730299
TI  - Loss of bcl-2 during the senescence exacerbates the impaired angiogenic functions
      in endothelial cells by deteriorating the mitochondrial redox state.
AB  - Ageing is an important risk factor for ischemic cardiovascular diseases, although
      its underlying molecular mechanisms remain to be elucidated. Here, we report a
      crucial role of Bcl-2 in the impaired angiogenic functions in senescent
      endothelial cells (ECs) by modulating the mitochondrial redox state. Cellular
      senescence impaired angiogenic functions in ECs without attenuating the mitogen
      activated protein kinase or Akt signaling, and vascular endothelial growth factor
      receptor 2 or Tie-2 expressions. We identified that Bcl-2 expression was markedly
      reduced in 3 independent models for senescent ECs, and pharmacological
      inhibition, as well as small interfering RNA-mediated gene silencing of Bcl-2,
      significantly impaired the angiogenic functions in young ECs. Bcl-2 has an
      antioxidative role by locating the glutathione at mitochondria, and we found that
      mitochondrial oxidative stress was significantly augmented in senescent ECs, in
      association with reduced mitochondria-associated glutathione. Transfection of Bcl
      2 in senescent ECs significantly reduced the mitochondrial oxidative stress,
      restored the mitochondrial membrane potential, and improved the angiogenic
      capacity. Furthermore, gene transfer of Bcl-2 using adenovirus significantly
      improved the in vivo angiogenesis in the Matrigel plugs implanted into aged mice,
      whereas the Bcl-2 inhibitor reduced the angiogenesis in the Matrigel plugs
      implanted into young mice. Together, Bcl-2 plays a crucial role in the regulation
      of the mitochondrial redox state in ECs, and, thus, loss of Bcl-2 during the
      senescence exacerbates the impaired angiogenesis by augmenting the mitochondrial
      oxidative stress.

PMID- 21730300
TI  - Is it ethical to perform irreversible renal denervation before a trial of low
      sodium intake for treatment-resistant hypertension?

PMID- 21730301
TI  - Exacerbated pulmonary arterial hypertension and right ventricular hypertrophy in
      animals with loss of function of extracellular superoxide dismutase.
AB  - Studies have demonstrated that increased oxidative stress contributes to the
      pathogenesis and the development of pulmonary artery hypertension (PAH).
      Extracellular superoxide dismutase (SOD3) is essential for removing extracellular
      superoxide anions, and it is highly expressed in lung tissue. However, it is not
      clear whether endogenous SOD3 can influence the development of PAH. Here we
      examined the effect of SOD3 knockout on hypoxia-induced PAH in mice and a loss-of
      function SOD3 gene mutation (SOD3(E124D)) on monocrotaline (40 mg/kg)-induced PAH
      in rats. SOD3 knockout significantly exacerbated 2 weeks of hypoxia-induced right
      ventricular (RV) pressure and RV hypertrophy, whereas RV pressure in SOD3
      knockout mice under normoxic conditions is similar to wild-type controls. In
      untreated control rats at age of 8 weeks, there was no significant difference
      between wild-type and SOD3(E124D) rats in RV pressure and the ratio of RV
      weight:left ventricular weight (0.25+/-0.02 in wild-type rats versus 0.25+/-0.01
      in SOD3(E124D) rats). However, monocrotaline caused significantly greater
      increases of RV pressure in SOD3(E124D) rats (48.6+/-1.8 mm Hg in wild-type
      versus 57.5+/-3.1 mm Hg in SOD3(E124D) rats), of the ratio of RV weight:left
      ventricular weight (0.41+/-0.01 versus 0.50+/-0.09; P<0.05), and of the
      percentage of fully muscularized small arterioles in SOD3(E124D) rats (55.2+/
      2.3% versus 69.9+/-2.6%; P<0.05). Together, these findings indicate that the
      endogenous SOD3 has no role in the development of PAH under control conditions
      but plays an important role in protecting the lung from the development of PAH
      under stress conditions.

PMID- 21730302
TI  - Reducing the global burden of ischemic heart disease and stroke: a challenge for
      the cardiovascular community and the United Nations.

PMID- 21730303
TI  - Protein kinase D2 controls cardiac valve formation in zebrafish by regulating
      histone deacetylase 5 activity.
AB  - BACKGROUND: The molecular mechanisms that guide heart valve formation are not
      well understood. However, elucidation of the genetic basis of congenital heart
      disease is one of the prerequisites for the development of tissue-engineered
      heart valves. METHODS AND RESULTS: We isolated here a mutation in zebrafish,
      bungee (bng(jh177)), which selectively perturbs valve formation in the embryonic
      heart by abrogating endocardial Notch signaling in cardiac cushions. We found by
      positional cloning that the bng phenotype is caused by a missense mutation
      (Y849N) in zebrafish protein kinase D2 (pkd2). The bng mutation selectively
      impairs PKD2 kinase activity and hence Histone deacetylase 5 phosphorylation,
      nuclear export, and inactivation. As a result, the expression of Histone
      deacetylase 5 target genes Kruppel-like factor 2a and 4a, transcription factors
      known to be pivotal for heart valve formation and to act upstream of Notch
      signaling, is severely downregulated in bungee (bng) mutant embryos. Accordingly,
      the expression of Notch target genes, such as Hey1, Hey2, and HeyL, is severely
      decreased in bng mutant embryos. Remarkably, downregulation of Histone
      deacetylase 5 activity in homozygous bng mutant embryos can rescue the mutant
      phenotype and reconstitutes notch1b expression in atrioventricular endocardial
      cells. CONCLUSIONS: We demonstrate for the first time that proper heart valve
      formation critically depends on Protein kinase D2-Histone deacetylase 5-Kruppel
      like factor signaling.

PMID- 21730304
TI  - Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis
      by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence
      that the effects are not apolipoprotein E dependent.
AB  - BACKGROUND: We previously demonstrated that macrophage low-density lipoprotein
      receptor (LDLR)-related protein 1 (LRP1) deficiency increases atherosclerosis
      despite antiatherogenic changes including decreased uptake of remnants and
      increased secretion of apolipoprotein E (apoE). Thus, our objective was to
      determine whether the atheroprotective effects of LRP1 require interaction with
      apoE, one of its ligands with multiple beneficial effects. METHODS AND RESULTS:
      We examined atherosclerosis development in mice with specific deletion of
      macrophage LRP1 (apoE(-/-) MPhiLRP1(-/-)) and in LDLR(-/-) mice reconstituted
      with apoE(-/-) MPhiLRP1(-/-) bone marrow. The combined absence of apoE and LRP1
      promoted atherogenesis more than did macrophage apoE deletion alone in both apoE
      producing LDLR(-/-) mice (+88%) and apoE(-/-) mice (+163%). The lesions of both
      mouse models with apoE(-/-) LRP1(-/-) macrophages had increased macrophage
      content. In vitro, apoE and LRP1 additively inhibit macrophage apoptosis.
      Furthermore, there was excessive accumulation of apoptotic cells in lesions of
      both LDLR(-/-) mice (+110%) and apoE(-/-) MPhiLRP1(-/-) mice (+252%). The
      apoptotic cell accumulation was partially due to decreased efferocytosis as the
      ratio of free to cell-associated apoptotic nuclei was 3.5-fold higher in lesions
      of apoE(-/-) MPhiLRP1(-/-) versus apoE(-/-) mice. Lesion necrosis was also
      increased (6 fold) in apoE(-/-) MPhiLRP1(-/-) versus apoE(-/-) mice. Compared
      with apoE(-/-) mice, the spleens of apoE(-/-) MPhiLRP1(-/-) mice contained 1.6-
      and 2.4-fold more total and Ly6-C(high) monocytes. Finally, there were 3.6- and
      2.4-fold increases in Ly6-C(high) and CC-chemokine receptor 2-positive cells in
      lesions of apoE(-/-) MPhiLRP1(-/-) versus apoE(-/-) mice, suggesting that
      accumulation of apoptotic cells enhances lesion development and macrophage
      content by promoting the recruitment of inflammatory monocytes. CONCLUSION: Low
      density lipoprotein receptor protein 1 exerts antiatherogenic effects via
      pathways independent of apoE involving macrophage apoptosis and monocyte
      recruitment.

PMID- 21730305
TI  - Exploring determinants of secular decreases in childhood blood pressure and
      hypertension.
AB  - BACKGROUND: Childhood blood pressure is largely uninfluenced by medical treatment
      and behavioral changes associated with hypertension diagnosis. Examining secular
      trends in childhood blood pressure and its contributing factors will help us
      better understand population-level determinants of blood pressure and
      hypertension. METHODS AND RESULTS: Data were from 4 waves of the Korean National
      Health and Nutrition Examination Survey between 1998 and 2008, including a total
      of 5909 boys and girls 10 to 19 years of age. Over the past 10 years, age- and
      height-adjusted mean systolic blood pressure decreased substantially from 115.6
      to 106.9 mm Hg (by 8.7 mm Hg) among boys and from 111.8 to 101.8 mm Hg (by 10.0
      mm Hg) among girls. Associated childhood hypertension and
      prehypertension/hypertension prevalences decreased by 52% to 86%. These
      remarkable decreases were found among all age and socioeconomic groups and were
      not explained by secular changes in childhood obesity (body mass index and waist
      circumferences), health behaviors (cigarette smoking and physical activity),
      nutritional factors (sodium, potassium, total energy, protein, and fat intake),
      psychological factors (perceived stress and sleep duration), and sociodemographic
      factors (annual household income and family size). CONCLUSIONS: We observed
      important population declines in blood pressure in Korea over a 10-year period in
      children 10 to 19 years of age, but the likely causes for these secular trends
      remain to be determined.

PMID- 21730306
TI  - Global variation in the relative burden of stroke and ischemic heart disease.
AB  - BACKGROUND: Although stroke and ischemic heart disease (IHD) have several well
      established risk factors in common, the extent of global variation in the
      relative burdens of these forms of vascular disease and reasons for any observed
      variation are poorly understood. METHODS AND RESULTS: We analyzed mortality and
      disability-adjusted life-year loss rates from stroke and IHD, as well as national
      estimates of vascular risk factors that have been developed by the World Health
      Organization Burden of Disease Program. National income data were derived from
      World Bank estimates. We used linear regression for univariable analysis and the
      Cuzick test for trends. Among 192 World Health Organization member countries,
      stroke mortality rates exceeded IHD rates in 74 countries (39%), and stroke
      disability-adjusted life-year loss rates exceeded IHD rates in 62 countries
      (32%). Stroke mortality ranged from 12.7% higher to 27.2% lower than IHD, and
      stroke disability-adjusted life-year loss rates ranged from 6.2% higher to 10.2%
      lower than IHD. Stroke burden was disproportionately higher in China, Africa, and
      South America, whereas IHD burden was higher in the Middle East, North America,
      Australia, and much of Europe. Lower national income was associated with higher
      relative mortality (P<0.001) and burden of disease (P=0.001) from stroke.
      Diabetes mellitus prevalence and mean serum cholesterol were each associated with
      greater relative burdens from IHD even after adjustment for national income.
      CONCLUSIONS: There is substantial global variation in the relative burden of
      stroke compared with IHD. The disproportionate burden from stroke for many lower
      income countries suggests that distinct interventions may be required.

PMID- 21730308
TI  - Increased vertebral artery tortuosity index is associated with adverse outcomes
      in children and young adults with connective tissue disorders.
AB  - BACKGROUND: Arterial tortuosity is described as a common and distinctive feature
      of Loeys-Dietz syndrome (LDS), yet reports on arterial tortuosity are based on
      qualitative observations and none have investigated an association between
      tortuosity and cardiovascular outcomes in LDS or other connective tissue
      disorders. METHODS AND RESULTS: We performed a retrospective analysis of 90
      patients <=50 years of age with Marfan syndrome, LDS, Ehlers-Danlos syndrome, or
      nonspecific connective tissue disorder who underwent thoracic contrast-enhanced
      magnetic resonance angiography. Controls (n=30) underwent magnetic resonance
      imaging to exclude arrhythmogenic right ventricular dysplasia. Using a volume
      rendered angiogram, vertebral arteries were measured along the curvature of the
      vessel (actual length) and linearly (straight length), and distance factor was
      calculated: [(actual/straight length-1)*100]. Each subject's maximum distance
      factor was designated the Vertebral Tortuosity Index (VTI). The VTI was compared
      among diagnostic groups and among patients with cardiac surgery, dissection, and
      death. Median age at magnetic resonance imaging was 19.6 years (range 0.2 to
      50.1). VTI interrater reliability was excellent (intraclass correlation
      coefficient =0.987). The VTI was higher in Marfan syndrome (n=57, median 26;
      interquartile range 10 to 49) and LDS (n=13, median 58; interquartile range 18 to
      92) compared with controls (median 4.5; interquartile range 3 to 6; P<0.001 for
      both). Higher VTI was associated with younger age at surgery even when
      controlling for root size (adjusted P=0.002). Vertebral tortuosity index >=50 was
      associated with earlier age at dissection and death compared with VTI <50
      (P=0.001 versus P<0.001). We found no difference in age at surgery, dissection,
      or death in Marfan syndrome compared with LDS. CONCLUSION: Arterial tortuosity
      measured by magnetic resonance angiography is a reproducible marker of adverse
      cardiovascular outcomes in connective tissue disorders.

PMID- 21730307
TI  - Rapid, direct effects of statin treatment on arterial redox state and nitric
      oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated
      endothelial nitric oxide synthase coupling.
AB  - BACKGROUND: Treatment with statins improves clinical outcome, but the exact
      mechanisms of pleiotropic statin effects on vascular function in human
      atherosclerosis remain unclear. We examined the direct effects of atorvastatin on
      tetrahydrobiopterin-mediated endothelial nitric oxide (NO) synthase coupling in
      patients with coronary artery disease. METHODS AND RESULTS: We first examined the
      association of statin treatment with vascular NO bioavailability and arterial
      superoxide (O(2)(.-)) in 492 patients undergoing coronary artery bypass graft
      surgery. Then, 42 statin-naive patients undergoing elective coronary artery
      bypass graft surgery were randomized to atorvastatin 40 mg/d or placebo for 3
      days before surgery to examine the impact of atorvastatin on endothelial function
      and O(2)(.-) generation in internal mammary arteries. Finally, segments of
      internal mammary arteries from 26 patients were used in ex vivo experiments to
      evaluate the statin-dependent mechanisms regulating the vascular redox state.
      Statin treatment was associated with improved vascular NO bioavailability and
      reduced O(2)(.-) generation in internal mammary arteries. Oral atorvastatin
      increased vascular tetrahydrobiopterin bioavailability and reduced basal and N
      nitro-l-arginine methyl ester-inhibitable O(2)(.-) in internal mammary arteries
      independently of low-density lipoprotein lowering. In ex vivo experiments,
      atorvastatin rapidly improved vascular tetrahydrobiopterin bioavailability by
      upregulating GTP-cyclohydrolase I gene expression and activity, resulting in
      improved endothelial NO synthase coupling and reduced vascular O(2)(.-). These
      effects were reversed by mevalonate, indicating a direct effect of vascular
      hydroxymethylglutaryl-coenzyme A reductase inhibition. CONCLUSIONS: This study
      demonstrates for the first time in humans the direct effects of statin treatment
      on the vascular wall, supporting the notion that this effect is independent of
      low-density lipoprotein lowering. Atorvastatin directly improves vascular NO
      bioavailability and reduces vascular O(2)(.-) through tetrahydrobiopterin
      mediated endothelial NO synthase coupling. These findings provide new insights
      into the mechanisms mediating the beneficial vascular effects of statins in
      humans. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01013103.

PMID- 21730309
TI  - Development and validation of a risk calculator for prediction of cardiac risk
      after surgery.
AB  - BACKGROUND: Perioperative myocardial infarction or cardiac arrest is associated
      with significant morbidity and mortality. The Revised Cardiac Risk Index is
      currently the most commonly used cardiac risk stratification tool; however, it
      has several limitations, one of which is its relatively low discriminative
      ability. The objective of the present study was to develop and validate a
      predictive cardiac risk calculator. METHODS AND RESULTS: Patients who underwent
      surgery were identified from the American College of Surgeons' 2007 National
      Surgical Quality Improvement Program database, a multicenter (>250 hospitals)
      prospective database. Of the 211 410 patients, 1371 (0.65%) developed
      perioperative myocardial infarction or cardiac arrest. On multivariate logistic
      regression analysis, 5 predictors of perioperative myocardial infarction or
      cardiac arrest were identified: type of surgery, dependent functional status,
      abnormal creatinine, American Society of Anesthesiologists' class, and increasing
      age. The risk model based on the 2007 data set was subsequently validated on the
      2008 data set (n=257 385). The model performance was very similar between the
      2007 and 2008 data sets, with C statistics (also known as area under the receiver
      operating characteristic curve) of 0.884 and 0.874, respectively. Application of
      the Revised Cardiac Risk Index to the 2008 National Surgical Quality Improvement
      Program data set yielded a relatively lower C statistic (0.747). The risk model
      was used to develop an interactive risk calculator. CONCLUSIONS: The cardiac risk
      calculator provides a risk estimate of perioperative myocardial infarction or
      cardiac arrest and is anticipated to simplify the informed consent process. Its
      predictive performance surpasses that of the Revised Cardiac Risk Index.

PMID- 21730310
TI  - Intermittent cardiogenic shock in a man with mechanical prosthesis of the aortic
      valve.

PMID- 21730311
TI  - Letter by Leurent et al regarding article, "Prevalence and clinical significance
      of papillary muscle infarction detected by late gadolinium-enhanced magnetic
      resonance imaging in patients with ST-segment elevation myocardial infarction".

PMID- 21730312
TI  - Letter by Halcox regarding article, "OMEGA, a randomized, placebo-controlled
      trial to test the effect of highly purified omega-3 fatty acids on top of modern
      guideline-adjusted therapy after myocardial infarction".

PMID- 21730313
TI  - Letter by Papageorgiou et al regarding article, "OMEGA, a randomized, placebo
      controlled trial to test the effect of highly purified omega-3 fatty acids on top
      of modern guideline-adjusted therapy after myocardial infarction".

PMID- 21730314
TI  - Letter by Alter and Rupp regarding article, "OMEGA, a randomized, placebo
      controlled trial to test the effect of highly purified omega-3 fatty acids on top
      of modern guideline-adjusted therapy after myocardial infarction".

PMID- 21730317
TI  - Omnes viae Romam ducunt: Asymptomatic cardiac and noncardiac organ system
      dysfunction leads to heart failure.

PMID- 21730318
TI  - p53-upregulated modulator of apoptosis (PUMA): a novel proapoptotic molecule in
      the failing heart.

PMID- 21730319
TI  - The mitral valve in hypertrophic cardiomyopathy: it's a long story.

PMID- 21730320
TI  - Tensions rise and blood flows over dysfunctional fat.

PMID- 21730321
TI  - Functional genomics applied to cardiovascular medicine.

PMID- 21730322
TI  - Atrial fibrillation: outpatient presentation and management.

PMID- 21730323
TI  - Cardiovascular complications of cutis laxa syndrome: successful diagnosis and
      surgical management.

PMID- 21730324
TI  - Bacterial scaffolds assemble novel higher-order complexes to reengineer
      eukaryotic cell processes.
AB  - Many microbial pathogens use specialized secretion systems to inject proteins
      referred to as effectors directly into eukaryotic host cells. These effectors
      directly target various eukaryotic signaling pathways and cellular processes,
      often by mimicking the activity of host cell proteins. Effectors of pathogenic
      Escherichia coli and Salmonella typhimurium can also act as molecular scaffolds
      that not only recruit but also directly regulate the activity and localization of
      multiple eukaryotic proteins. By assembling and localizing disparate signaling
      pathways, the bacteria can reengineer host cell processes to generate novel
      processes not previously observed in eukaryotic cells.

PMID- 21730325
TI  - Sequential phosphorylation of smoothened transduces graded hedgehog signaling.
AB  - The correct interpretation of a gradient of the morphogen Hedgehog (Hh) during
      development requires phosphorylation of the Hh signaling activator Smoothened
      (Smo); however, the molecular mechanism by which Smo transduces graded Hh
      signaling is not well understood. We show that regulation of the phosphorylation
      status of Smo by distinct phosphatases at specific phosphorylated residues
      creates differential thresholds of Hh signaling. Phosphorylation of Smo was
      initiated by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA)
      and further enhanced by casein kinase I (CKI). We found that protein phosphatase
      1 (PP1) directly dephosphorylated PKA-phosphorylated Smo to reduce signaling
      mediated by intermediate concentrations of Hh, whereas PP2A specifically
      dephosphorylated PKA-primed, CKI-phosphorylated Smo to restrict signaling by high
      concentrations of Hh. We also established a functional link between sequentially
      phosphorylated Smo species and graded Hh activity. Thus, we propose a sequential
      phosphorylation model in which precise interpretation of morphogen concentration
      can be achieved upon versatile phosphatase-mediated regulation of the
      phosphorylation status of an essential activator in developmental signaling.

PMID- 21730327
TI  - Serotonin and the autisms: a red flag or a red herring?

PMID- 21730326
TI  - Identification of a lysosomal pathway that modulates glucocorticoid signaling and
      the inflammatory response.
AB  - The antimalaria drug chloroquine has been used as an anti-inflammatory agent for
      treating systemic lupus erythematosus and rheumatoid arthritis. We report that
      chloroquine promoted the transrepression of proinflammatory cytokines by the
      glucocorticoid receptor (GR). In a mouse collagen-induced arthritis model,
      chloroquine enhanced the therapeutic effects of glucocorticoid treatment. By
      inhibiting lysosome function, chloroquine synergistically activated
      glucocorticoid signaling. Lysosomal inhibition by either bafilomycin A1 (an
      inhibitor of the vacuolar adenosine triphosphatase) or knockdown of transcription
      factor EB (TFEB, a master activator of lysosomal biogenesis) mimicked the effects
      of chloroquine. The abundance of the GR, as well as that of the androgen receptor
      and estrogen receptor, correlated with changes in lysosomal biogenesis. Thus, we
      showed that glucocorticoid signaling is regulated by lysosomes, which provides a
      mechanistic basis for treating inflammation and autoimmune diseases with a
      combination of glucocorticoids and lysosomal inhibitors.

PMID- 21730328
TI  - Is autism, at least in part, a disorder of fetal programming?

PMID- 21730329
TI  - Isolation and characterization of microsatellite loci from apomictic Hypericum
      perforatum (Hypericaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed to study the origins
      and evolution of apomictic Hypericum perforatum, a polyploid invasive perennial
      herb indigenous to Europe that produces compounds of medicinal/pharmaceutical
      importance. METHODS AND RESULTS: Eleven primer sets were developed using a non
      radioactive protocol. All loci were polymorphic, showing from 2 to 9 alleles per
      locus. Observed and expected heterozygosity averaged 0.861 and 0.772,
      respectively, across four studied populations. Most primers also amplified
      successfully in eight other Hypericum species. CONCLUSIONS: Markers developed in
      this study provide genetic tools for studies of apomixis and invasiveness, both
      on the intra- and interspecific levels.

PMID- 21730330
TI  - A set of novel microsatellite markers developed for the traditional Tibetan
      medicinal plant Halenia elliptica (Gentianaceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed in the traditional
      Tibetan medicinal plant Halenia elliptica D. Don to investigate its genetic
      diversity and population genetic structure. METHODS AND RESULTS: Using the Fast
      Isolation by AFLP of Sequences Containing (FIASCO) repeats protocol, 24 primer
      sets were identified in two wild populations. Of these primers, 12 displayed
      polymorphisms and 12 were monomorphic. The number of alleles per locus ranged
      from 2 to 6, with a mean of 3.9. The expected (H(E)) and observed (H(O))
      heterozygosities ranged from 0.191 to 0.784 and from 0.417 to 0.917,
      respectively. All these primers successfully amplified in two close relatives of
      H. elliptica, Swertia bimaculata (Siebold & Zucc.) Hook. f. & Thomson ex C. B.
      Clarke and S. tetraptera Maxim. CONCLUSIONS: These markers will facilitate
      further studies on the population genetics of Halenia elliptica and its allied
      species.

PMID- 21730331
TI  - Isolation and characterization of 10 microsatellite loci from Korean Leontopodium
      japonicum (Asteraceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed for the alpine plant
      Leontopodium japonicum to evaluate its population genetics structure as a means
      for devising future conservation strategies. METHODS AND RESULTS: Ten polymorphic
      microsatellite markers were developed in Korean populations of L. japonicum.
      Genetic diversity was analyzed among 38 individuals from two populations.
      Overall, each locus had 3 to 17 alleles, and their observed and expected
      heterozygosities ranged from 0.0000 to 0.8750 and from 0.0000 to 0.8929,
      respectively. CONCLUSIONS: The microsatellite markers described here are valuable
      tools for population genetics research of L. japonicum. They can be used to
      obtain information about suitable management strategies for protecting other
      related and endangered "edelweiss" species.

PMID- 21730332
TI  - Newly developed primers for complete ycf1 amplification in Pinus (Pinaceae)
      chloroplasts with possible family-wide utility.
AB  - PREMISE OF THE STUDY: Primers were designed to amplify the highly variable locus
      ycf1 from all 11 subsections of Pinus to facilitate plastome assemblies based on
      short sequence reads as well as future phylogenetic and population genetic
      analyses. METHODS AND RESULTS: Primer design was based on alignment of 33 Pinus
      and four Pinaceae plastomes with mostly incomplete ycf1 sequences. Sanger
      sequencing of 12 Pinus accessions resulted in open reading frames ranging in size
      from 5.2 to 6.1 kbp. Highest sequence diversity was identified in two regions
      totaling 5.5 kbp aligned length, which can be targeted in all pine subsections
      with three primer combinations. Preliminary results suggest the primers described
      also amplify homologous targets in the broader Pinaceae. CONCLUSIONS: The
      successful design and implementation of PCR primers spanning the large, variable
      locus ycf1 in Pinus represents the development of a valuable tool in pine genetic
      studies, and should facilitate studies throughout Pinaceae.

PMID- 21730333
TI  - Asymmetric single-strand conformation polymorphism: an accurate and cost
      effective method to amplify and sequence allelic variants.
AB  - PREMISE OF THE STUDY: An efficient alternative strategy to conventional cloning
      was needed to generate high-quality DNA sequences from a variety of nuclear
      orthologs for phylogenetic studies. This method would facilitate studies and
      minimize technical problems typically encountered in cloning methodologies.
      METHODS: We tested a variety of single-strand conformation polymorphism (SSCP)
      protocols including purified and unpurified symmetric and asymmetric PCR, loading
      buffers, and electrophoresis conditions (buffers, matrix, running time,
      temperature). Results obtained from direct SSCP band sequencing were compared to
      those obtained from cloning. KEY RESULTS: Our optimized protocol uses asymmetric
      PCR, with the majority of the samples run in polyacrylamide gel electrophoresis
      (PAGE). It consistently separated PCR products from 450 to 1200 bp. CONCLUSIONS:
      Asymmetric PCR single-strand conformation polymorphism is an efficient
      alternative technique for isolating allelic variants of highly heterozygous
      individuals, with its greatest applications in sequencing allopolyploids. It
      eliminates two common problems encountered in cloning: PCR recombination and
      heteroduplex fixation. In addition, our protocol greatly lowers costs and time
      associated with procedures.

PMID- 21730334
TI  - Ontogeny of floral organs in flax (Linum usitatissimum; Linaceae).
AB  - PREMISE OF THE STUDY: Flax (Linum usitatissimum) is an important crop worldwide;
      however, a detailed study on flower development of this species is lacking. Here
      we describe the pattern of initiation and a program of key developmental events
      in flax flower ontogeny. This study provides important fundamental information
      for future research in various aspects of flax biology and biotechnology.
      METHODS: Floral buds and organs were measured throughout development and examined
      using scanning electron microscopy. KEY RESULTS: Floral organs were initiated in
      the following sequence: sepals, stamens and petals, gynoecium, and nectaries. The
      five sepals originated in a helical pattern, followed evidently by simultaneous
      initiation of five stamens and five petals, the former opposite of the sepals and
      the latter alternate to them. The gynoecium, with five carpels, was produced from
      the remaining, central region of the floral apex. Stamens at early stages were
      dominated by anther growth but filaments elongated rapidly shortly before
      anthesis. Early gynoecium development occurred predominantly in the ovary, and
      ovule initiation began prior to enclosure of carpels. A characteristic feature
      was the twisted growth of styles, accompanied by the differentiation of papillate
      stigmas. Petal growth lagged behind that of other floral organs, but petals
      eventually grew rapidly to enclose the inner whorls after style elongation. Flask
      shaped nectaries bearing stomata developed on the external surface of the
      filament bases. CONCLUSIONS: This is the first detailed study on flax floral
      organ development and has established a key of 12 developmental stages, which
      should be useful to flax researchers.

PMID- 21730335
TI  - Multiple mechanisms enable invasive species to suppress native species.
AB  - PREMISE OF THE STUDY: Invasive plants represent a significant threat to ecosystem
      biodiversity. To decrease the impacts of invasive species, a major scientific
      undertaking of the last few decades has been aimed at understanding the
      mechanisms that drive invasive plant success. Most studies and theories have
      focused on a single mechanism for predicting the success of invasive plants and
      therefore cannot provide insight as to the relative importance of multiple
      interactions in predicting invasive species' success. METHODS: We examine four
      mechanisms that potentially contribute to the success of invasive velvetgrass
      Holcus lanatus: direct competition, indirect competition mediated by mammalian
      herbivores, interference competition via allelopathy, and indirect competition
      mediated by changes in the soil community. Using a combination of field and
      greenhouse approaches, we focus on the effects of H. lanatus on a common species
      in California coastal prairies, Erigeron glaucus, where the invasion is most
      intense. KEY RESULTS: We found that H. lanatus had the strongest effects on E.
      glaucus via direct competition, but it also influenced the soil community in ways
      that feed back to negatively influence E. glaucus and other native species after
      H. lanatus removal. CONCLUSIONS: This approach provided evidence for multiple
      mechanisms contributing to negative effects of invasive species, and it
      identified when particular strategies were most likely to be important. These
      mechanisms can be applied to eradication of H. lanatus and conservation of
      California coastal prairie systems, and they illustrate the utility of an
      integrated set of experiments for determining the potential mechanisms of
      invasive species' success.

PMID- 21730336
TI  - Rarity as a life-history correlate in Dudleya (Crassulaceae).
AB  - PREMISE OF THE STUDY: Differences in rarity among species can be caused by
      adaptation to local conditions along with correlated evolution in characters that
      limit geographic range size. For this kind of divergence, the resulting species
      differ in their ability to thrive in varying environments. Because rare species
      are more prone to extinction than widespread species, trade-offs in life history
      predispose the resulting lineages to clade selection. METHODS: Nine Dudleya
      species live in the Santa Monica Mountains: five neoendemics, one species
      intermediate in rarity, and three with broader ranges. Life-history traits were
      correlated against one another. To understand habitat dependence, the species
      were grown in an inland garden and in a coastal garden, and the disparity in
      growth and reproduction in the two gardens was compared among species. KEY
      RESULTS: Rare species reproduced earlier and grew to be smaller than common
      species. The small body size of the rare species was correlated with small
      reproductive outputs compared with those of the large-bodied common species. The
      growth disparity between plants in the two gardens was greatest for the rare
      species. The rare species had a lower tolerance for hot, dry conditions compared
      with the common species. In the Santa Monica Mountains, the habitat conditions
      required by the rare species are not as prevalent as those of the common species.
      CONCLUSIONS: The data are consistent with the view that differences in life
      histories constrained by trade-offs affect range size. Such differences in rarity
      become the grist for clade selection at the scale of macroevolution.

PMID- 21730337
TI  - Geographic distribution of genetic variation among native and introduced
      populations of Chinese tallow tree, Triadica sebifera (Euphorbiaceae).
AB  - PREMISE OF THE STUDY: Invasive plants often display genetically determined
      variation in patterns of growth and resource allocation between native and
      introduced genotypes, as well as among genotypes within different regions of the
      introduced range. We examined patterns of genetic variation within and among
      native and introduced populations of the tetraploid Chinese tallow tree (Triadica
      sebifera, Euphorbiaceae) to determine whether nonselective evolutionary processes
      or the introduction history could contribute to previously observed phenotypic
      differences between native and introduced populations as well as among introduced
      populations. METHODS: We used six microsatellite markers to study 12 native
      populations in China, 51 introduced populations in the southeastern USA, and one
      introduced population in Australia. KEY RESULTS: Genetic diversity was greater
      within and among native populations than introduced populations. Within the
      southeastern USA, populations in Georgia and South Carolina differed
      substantially in their genetic composition and had greater genetic diversity than
      the rest of the southeastern USA. Greater genetic similarity between some
      populations in the native range and introduced range indicate a common provenance
      for Georgia and South Carolina populations that could have come from any of
      several western or southern Chinese populations and a different provenance for
      other southeastern USA populations and the Australian population, which were most
      similar to more northeastern Chinese populations. CONCLUSIONS: Differences among
      introduced populations in potentially adaptive traits (e.g., herbivore tolerance,
      herbivore resistance, growth rates) may result in part from the introduction
      history, in particular from differences present among source populations in the
      native range.

PMID- 21730338
TI  - Characterization of rhizosphere fungi from selenium hyperaccumulator and
      nonhyperaccumulator plants along the eastern Rocky Mountain Front Range.
AB  - PREMISE OF STUDY: Selenium-hyperaccumulator plants can store over 1% (dry mass)
      Se in their tissues, despite the toxicity of this element at high concentrations
      across eukaryotes. These levels of Se can have widespread effects on the plant's
      ecological partners, including herbivores and pathogens. Still other partners
      seem to have coevolved Se tolerance. This is the first known study addressing the
      rhizosphere mycoflora of Se hyperaccumulators and aims to evaluate the
      rhizospheric fungal diversity and Se tolerance to further the knowledge of how
      these organisms interact with their host plants and survive in these extreme
      habitats. METHODS: Rhizosphere fungi were isolated from Se-hyperaccumulator and
      nonaccumulator plant species collected from five sites in Colorado and Wyoming;
      four seleniferous sites and one nonseleniferous site. 259 isolates were
      identified to genus or species and evaluated for Se tolerance. KEY RESULTS: Among
      the 24 represented genera, 11 comprised 86% of the isolates. The majority of
      isolates from the seleniferous sites were unaffected by 10 mg.L(-1) Se,
      irrespective of host plant (hyperaccumulator vs. nonaccumulator), while
      rhizosphere fungi from a control, nonseleniferous site were highly sensitive to
      Se at 10 mg.L(-1) and as a group were significantly less (alpha = 0.05) tolerant
      than the isolates from the seleniferous sites. CONCLUSIONS: Even though Se is a
      commonly used antifungal agent, these results suggest that rhizosphere fungi from
      seleniferous habitats have widespread Se tolerance, likely an adaptive advantage
      in their Se-rich habitat.

PMID- 21730339
TI  - Enhancing pollen competition by delaying stigma receptivity: pollen deposition
      schedules affect siring ability, paternal diversity, and seed production in
      Collinsia heterophylla (Plantaginaceae).
AB  - PREMISE OF THE STUDY: Even though pollen deposition schedules may have profound
      effects on the evolutionary outcome of pollen competition, few studies have
      investigated such effects in relation to pistil traits such as delayed stigma
      receptivity that enhance pollen competition. In Collinsia heterophylla, a largely
      outcrossing species with delayed stigma receptivity, we performed a series of
      controlled crosses involving several donors to understand how timing of pollen
      deposition influences siring ability, paternal diversity, and offspring fitness.
      METHODS: Pollen was applied to fully receptive stigmas either as mixtures or
      consecutively with or without a time lag to mimic cases with early or delayed
      stigma receptivity. We used a genetic marker to assess offspring paternity. KEY
      RESULTS: As expected, siring ability was affected by application order in crosses
      without a time lag, providing a first-donor advantage for pollen arriving on
      unreceptive stigmas. However, because pollen donor identity influenced siring
      ability, delaying stigma receptivity may still favor pollen of high competitive
      ability. In crosses on fully receptive pistils with a time lag of 24 h, a
      surprisingly high proportion of seeds (12-47%) were sired by pollen applied last.
      A novel finding was that pollen applied only once (as a mixture), mimicking
      delayed stigma receptivity, led to higher paternal diversity within progeny
      families, which was associated with increased seed production. CONCLUSIONS: Our
      results suggest fitness advantages of enhancing pollen competition by delaying
      stigma receptivity in C. heterophylla, particularly in relation to increased
      paternal diversity.

PMID- 21730340
TI  - The evolutionary history of Mimosa (Leguminosae): toward a phylogeny of the
      sensitive plants.
AB  - PREMISE OF THE STUDY: Large genera provide remarkable opportunities to
      investigate patterns of morphological evolution and historical biogeography in
      plants. A molecular phylogeny of the species-rich and morphologically and
      ecologically diverse genus Mimosa was generated to evaluate its infrageneric
      classification, reconstruct the evolution of a set of morphological characters,
      and establish the relationships of Old World species to the rest of the genus.
      METHODS: We used trnD-trnT plastid sequences for 259 species of Mimosa (ca. 50%
      of the total) to reconstruct the phylogeny of the genus. Six morphological
      characters (petiolar nectary, inflorescence type, number of stamens, number of
      petals, pollen type, and seismonasty) were optimized onto the molecular tree. KEY
      RESULTS: Mimosa was recovered as a monophyletic clade nested within the
      Piptadenia group and includes the former members of Schrankia, corroborating
      transfer of that genus to Mimosa. Although we found good support for several
      infrageneric groups, only one section (Mimadenia) was recovered as monophyletic.
      All but one of the morphological characters analyzed showed high levels of
      homoplasy. High levels of geographic structure were found, with species from the
      same area tending to group together in the phylogeny. Old World species of Mimosa
      form a monophyletic clade deeply nested within New World groups, indicating
      recent (6-10 Ma) long-distance dispersal. CONCLUSIONS: Although based on a single
      plastid region, our results establish a preliminary phylogenetic framework for
      Mimosa that can be used to infer patterns of morphological evolution and
      relationships and which provides pointers toward a revised infrageneric
      classification.

PMID- 21730341
TI  - Limb-girdle myasthenia gravis in a 10-year-old girl: a case report.
AB  - A 10-year-old girl presented with progressive proximal limb muscle weakness
      without facial, ocular, or bulbar muscle involvement. There was no fatigability
      or diurnal fluctuation in symptoms. Her weakness worsened with febrile illnesses
      and recovered with accruing disabilities over a few weeks. Serum creatine kinase
      levels and muscle biopsy were normal. A significant decrement on repetitive nerve
      stimulation test and positive response to therapeutic neostigmine challenge test
      confirmed the diagnosis of limb-girdle myasthenia. She responded well to
      corticosteroids and thymectomy, demonstrating a likely autoimmune etiology. This
      case highlights the long-term fluctuations in a case of myasthenia gravis and the
      need for a high index of suspicion for myasthenia in children presenting with
      unexplained muscle weakness, even in the absence of typical features such as
      fatigability, diurnal fluctuation, and oculobulbar weakness.

PMID- 21730342
TI  - Cats, frogs, and snakes: early concepts of neural tube defects.
AB  - Disturbed neurulation fascinated scientists of all times. In Egypt, anencephalic
      infants were venerated as animal-headed gods. Roman law required them to be
      killed. The medieval world held the mother responsible, either because of assumed
      imagination or "miswatching," or because of suspected intercourse with animals or
      devils. Modern embryology and teratology began with the use of the microscope by
      Malpighi in 1672. Details of neural tube closure were described by Koelliker in
      1861 and by His in 1874. From 1822, genetic disease and familial recurrence due
      to insufficient nutrition were discerned and lower social class identified as a
      risk factor. It took a century to define the malnutrition as insufficient folate
      intake. The mandatory supplementation of folate in staple foods successfully
      reduced the incidence of neural tube defects in the United States, Australia,
      Canada, and Chile, but it was not adopted by most European countries.

PMID- 21730343
TI  - Deformation of the rodent optic nerve head and peripapillary structures during
      acute intraocular pressure elevation.
AB  - PURPOSE. To evaluate the effect of acutely elevated intraocular pressure (IOP) on
      retinal thickness and optic nerve head (ONH) structure in the rat eye by spectral
      domain-optical coherence tomography (SD-OCT). METHODS. Fourteen adult male Brown
      Norway rats were studied under anesthesia (ketamine/xylazine/acepromazine, 55:5:1
      mg/kg intramuscularly). Both eyes were imaged by SD-OCT on two baseline occasions
      several weeks before and again 2 and 4 weeks after the acute IOP imaging session.
      During the acute IOP session, SD-OCT imaging was performed 10 minutes after IOP
      was manometrically set at 15 mm Hg and then at 10, 30, and 60 minutes after IOP
      had been elevated to 50 mm Hg (n = 8) and again 10 and 30 minutes after IOP had
      been lowered back to 15 mm Hg (recovery). In two additional groups, IOP elevation
      was set to 70 mm Hg (n = 4) or 40 mm Hg (n = 2). Acute IOP results are reported
      for a pattern of 49 horizontal B-scans spanning a 20 degrees  square and follow
      up results for peripapillary circular B-scans. Retinal and retinal nerve fiber
      layer (RNFL) thicknesses were measured with custom software by manual image
      segmentation. Friedman and Dunn's tests were used to assess acute and longer-term
      effects of acute IOP elevation. RESULTS. Acute IOP elevation to 50 mm Hg caused
      rapid (within seconds) deformation of the ONH and peripapillary structures,
      including posterior displacement of the ONH surface and outward bowing of
      peripapillary tissue; retinal thickness decreased progressively from 10 to 30 to
      60 minutes by 16%, 18%, and 20% within the area of Bruch's membrane opening (BMO;
      P < 0.0001) by 8%, 9%, and 11% within the central 10 degrees  (excluding the BMO;
      P < 0.0001) but only by 1%, 2%, and 2.4% beyond the central 10 degrees  (P <
      0.0001). Recovery was progressive and nearly complete by 30 minutes. Acute IOP
      elevation to 40 and 70 mm Hg produced similar structural changes, but 70 mm Hg
      also interfered with retinal blood flow. There were no changes in peripapillary
      retinal or RNFL thickness (P = 0.08 and P = 0.16, respectively) measured 2 and 4
      weeks after acute elevation to 50 mm Hg. CONCLUSIONS. Acute IOP elevation in the
      rodent eye causes rapid, reversible posterior deformation of the ONH and thinning
      of the peripapillary retina, with only minimal retinal thinning beyond 5 degrees 
      of the ONH. No permanent changes in peripapillary retinal or RNFL thickness (for
      up to 1 month of follow-up) were caused by 60 minutes of IOP elevation to 50 mm
      Hg.

PMID- 21730344
TI  - Efficacy of a web-based intervention to improve and sustain knowledge and
      screening for amblyopia in primary care settings.
AB  - PURPOSE: To evaluate the efficacy of a physician-targeted website to improve
      knowledge and self-reported behavior relevant to strabismus and amblyopia
      ("vision") in primary care settings. METHODS: Eligible providers (filing Medicaid
      claims for at least eight well-child checks at ages 3 or 4 years, 1 year before
      study enrollment), randomly assigned to control (chlamydia and blood pressure) or
      vision groups, accessed four web-based educational modules, programmed to present
      interactive case vignettes with embedded questions and feedback. Each correct
      response, assigned a value of +1 to a maximum of +7, was used to calculate a
      summary score per provider. Responses from intervention providers (IPs) at
      baseline and two follow-up points were compared to responses to vision questions,
      taken at the end of the study, from control providers (CPs). RESULTS: Most IPs
      (57/65) responded at baseline and after the short delay (within 1 hour after
      baseline for 38 IPs). A subgroup (27 IPs and 42 CPs) completed all vision
      questions after a long delay averaging 1.8 years. Scores from IPs improved after
      the short delay (median score, 3 vs. 6; P = 0.0065). Compared to CPs, scores from
      IPs were similar at baseline (P = 0.6473) and higher after the short-term (P <
      0.0001) and long-term (P < 0.05) delay. CONCLUSIONS: Significant improvements
      after the short delay demonstrate the efficacy of the website and the potential
      for accessible, standardized vision education. Although improvements subsided
      over time, the IPs' scores did not return to baseline levels and were
      significantly better compared to CPs tested 1 to 3 years later.

PMID- 21730345
TI  - Reflectance decreases before thickness changes in the retinal nerve fiber layer
      in glaucomatous retinas.
AB  - PURPOSE: Glaucoma damages the retinal never fiber layer (RNFL). RNFL thickness,
      measured with optical coherence tomography (OCT), is often used in clinical
      assessment of the damage. In this study the relation between the RNFL reflectance
      and thickness at early stages of glaucoma was investigated. METHODS: A rat model
      of glaucoma was used that involved laser photocoagulation of the trabecular
      meshwork. The reflectance of the RNFL in an isolated retina was measured,
      followed by immunohistochemical staining of the axonal cytoskeleton. RNFL
      thickness was measured by confocal fluorescence imaging. RNFL reflectance was
      calculated for bundle areas located at radii of 0.22, 0.33, and 0.44 mm from the
      optic nerve head (ONH) center. Linear regression was used to study the relation
      between reflectance and thickness. For glaucomatous eyes, only those bundles with
      no apparent structural damage were used. RESULTS: Bundles in 11 control retinas
      and 10 treated retinas were examined. Bundle thickness of both groups at each
      radius was similar (P = 0.89). The reflectance of the bundles at radii of 0.33
      and 0.44 mm was found to be similar in both control and treated retinas (P >
      0.5). However, the reflectance of the bundles at the 0.22-mm radius decreased
      significantly in the treated group (P = 0.005). CONCLUSIONS: Elevation of
      intraocular pressure causes decrease in RNFL reflectance for bundles near the
      ONH. Change in RNFL reflectance precedes thinning of the RNFL. The results
      suggest that a decrease in RNFL reflectance near the ONH is an early sign of
      glaucomatous damage.

PMID- 21730347
TI  - Epiretinal membranes and incomplete posterior vitreous detachment in diabetic
      macular edema, detected by spectral-domain optical coherence tomography.
AB  - PURPOSE. To present the vitreoretinal interface in diabetic macular edema (DME)
      associated with both epiretinal membrane (ERM) and incomplete posterior vitreous
      detachment (PVD), as detected by spectral-domain optical coherence tomography (SD
      OCT). METHODS. In a retrospective study, findings were analyzed in one eye in
      consecutive patients. Excluded were eyes that had undergone vitreoretinal
      intervention or that had complete PVD or complete vitreous attachment. RESULTS.
      Of 44 eyes with DME and ERM, incomplete PVD was apparent in 23 (52.2%) eyes. A
      hyperreflective unified ERM/posterior vitreous cortex (PViC) membrane, or EVi
      membrane, was apparent in various sizes in 20 (87.0%) of the 23 eyes. This
      unified membrane (n = 20) was associated with vitreopapillary adherence in 19
      (82.6%) of 23 eyes. Two major OCT presentations (n = 23) were encountered:
      incomplete vitreopapillary detachment (n = 11; 25% of 44), with attachment to the
      macular ERM, and posterior vitreous detachment from the macula, associated with
      vitreopapillary adhesion (n = 10; 22.7%), in four different manifestations. In
      the remaining two eyes, there was no association between the ERM and the PViC.
      CONCLUSIONS. In eyes with DME, ERM, and incomplete PVD, the posterior cortical
      vitreous and ERM appeared as one united EVi membrane in various lengths in most
      eyes, typically associated with vitreopapillary adhesion. These findings may have
      clinical importance in the context of epimacular membrane characteristics and its
      removal in DME.

PMID- 21730346
TI  - Phosphoinositide 3-kinase signaling in retinal rod photoreceptors.
AB  - PURPOSE: Phosphoinositide 3-kinase (PI3K) consists of a p110 catalytic protein
      and a p85alpha regulatory protein, required for the stabilization and
      localization of p110-PI3K activity. The biological significance of PI3K was
      investigated in vertebrate rod photoreceptors by deleting its regulatory p85alpha
      protein and examining its role in photoreceptor structure, function, and protein
      trafficking. METHODS: Mice that expressed Cre recombinase in rods were bred to
      mice with a floxed p85alpha (pik3r1) regulatory subunit of PI3K to generate a
      conditional deletion of pik3r1 in rods. Functional and structural changes were
      determined by ERG and morphometric analysis, respectively. PI3K activity was
      measured in retinal homogenates immunoprecipitated with an anti-PY antibody. Akt
      activation was determined by Western blot analysis with a pAkt antibody. RESULTS:
      Light-induced stress increased PI3K activity in retinal immunoprecipitates and
      phosphorylation of Akt. There was no effect of pik3r1 deletion on retinal
      structure. However, twin flash electroretinography revealed a slight delay in
      recovery kinetics in pik3r1 knockout (KO) mice compared with wild-type controls.
      The movement of arrestin in the pik3r1 KO mice was slower than that in the wild
      type mouse retinas at 5 minutes of exposure to light. At 10 minutes of exposure,
      the ROS localization of arrestin was almost identical between the wild-type and
      pik3r1 KO mice. CONCLUSIONS: The results provide the first direct evidence that
      rods use PI3K-generated phosphoinositides for photoreceptor function. The lack of
      phenotype in pik3r1 KO rod photoreceptors suggests a redundant role in
      controlling PIP(3) synthesis.

PMID- 21730348
TI  - Characterization of the gastric immune response in cheetahs (Acinonyx jubatus)
      with Helicobacter-associated gastritis.
AB  - Captive cheetahs have an unusually severe progressive gastritis that is not
      present in wild cheetahs infected with the same strains of Helicobacter. This
      gastritis, when severe, has florid lymphocyte and plasma cell infiltrates in the
      epithelium and lamina propria with gland destruction, parietal cell loss, and, in
      some cases, lymphoid follicles. The local gastric immune response was
      characterized by immunohistochemistry in 21 cheetahs with varying degrees of
      gastritis. The character of the response was similar among types of gastritis
      except that cheetahs with severe gastritis had increased numbers (up to 70%) of
      lamina proprial CD79a+CD21- B cells. CD3+CD4+ T cells were present in the lamina
      propria, and CD3+CD8alpha+ T cells were within the glandular epithelium. Lymphoid
      aggregates had follicular differentiation with a central core of CD79a+/CD45R+ B
      cells and with an outer zone of CD3+ T cells that expressed both CD4 and CD8
      antigens. MHC II antigens were diffusely expressed throughout the glandular and
      superficial epithelium. No cheetah had evidence of autoantibodies against the
      gastric mucosa when gastric samples from 30 cheetahs with different degrees of
      gastritis were incubated with autologous and heterologous serum. These findings
      indicate that T-cell distribution in cheetahs is qualitatively similar to that in
      other species infected with Helicobacter but that large numbers of lamina propria
      activated B cells and plasma cells did distinguish cheetahs with severe
      gastritis. Further research is needed to determine whether alterations in the
      Th1:Th2 balance are the cause of this more plasmacytic response in some cheetahs.

PMID- 21730349
TI  - Psychosocial influences on safety climate: evidence from community pharmacies.
AB  - OBJECTIVE: To examine the relationship between psychosocial job characteristics
      and safety climate. DESIGN: Cross-sectional survey. SETTING: Community pharmacies
      in Great Britain. Participants A random sample of community pharmacists
      registered in Great Britain (n = 860). Survey instruments Effort-reward imbalance
      (ERI) indicator and Job Content Questionnaire (JCQ). Main outcome measures
      Pharmacy Safety Climate Questionnaire (PSCQ). RESULTS: The profile of scores from
      the ERI indicated a relatively high risk of adverse psychological effects. The
      profile of scores from the JCQ indicated both high demand on pharmacists and a
      high level of psychological and social resources to meet these demands. Path
      analysis confirmed a model in which the ERI and JCQ measures, as well as the type
      of pharmacy and pharmacist role, predicted responses to the PSCQ (chi(2)(36) =
      111.38, p < 0.001; Tucker-Lewis index = 0.96; comparative fit index = 0.98; root
      mean square error of approximation=0.05). Two general factors (effort vs reward
      and control vs demand) accounted for the effect of job characteristics on safety
      climate ratings; each had differential effects on the PSCQ scales. CONCLUSIONS:
      The safety climate in community pharmacies is influenced by perceptions of job
      characteristics, such as the level of job demands and the resources available to
      meet these demands. Hence, any efforts to improve safety should take into
      consideration the effect of the psychosocial work environment on safety climate.
      In addition, there is a need to address the presence of work-related stressors,
      which have the potential to cause direct or indirect harm to staff and service
      users. The findings of the current study provide a basis for future research to
      improve the safety climate and well-being, both in the pharmacy profession and in
      other healthcare settings.

PMID- 21730350
TI  - Matrix metalloproteinase-12 (MMP-12) SNP affects MMP activity, lung macrophage
      infiltration and protects against emphysema in COPD.
AB  - BACKGROUND: Recent genetic and animal studies have implicated matrix
      metalloproteinase-12 (MMP-12) in the pathogenesis of chronic obstructive
      pulmonary disease (COPD). It has previously been shown that individuals
      homozygous for the A/A allele of rs652438 in MMP-12 are over-represented among
      patients with severe COPD (n=1517). A study was undertaken to examine the
      functional basis of these findings. METHODS: rs652438 A and G variants were
      generated by site-directed mutagenesis and transfected into COS7 cells where they
      were expressed. Casein zymography and a specific FRET activity assay were used to
      compare MMP-12 activity between alleles. Cell migration was examined using a
      transwell assay. Patients from two COPD cohorts were genotyped for rs652438 and
      associated with inflammatory cell number in bronchoalveolar lavage fluid (n=10)
      and induced sputum (n=262); the emphysema score (n=1428) was assessed by CT
      scanning. RESULTS: Mean MMP activity was 2.95-fold higher by zymography
      (p=0.0049) and 3.45-fold higher by FRET assay (p=0.0001) for the A allele than
      the G allele. Mean migration of COS7 cells expressing the A allele was 2.31-fold
      greater than for those expressing the G allele (p=0.0001). Macrophage numbers
      were greater in bronchoalveolar lavage fluid (1.28-fold increase, p=0.033) and
      induced sputum (1.58-fold increase, p=0.083) of A/A individuals compared with A/G
      heterozygotes. The presence of the A allele was dose-dependently associated with
      increased emphysema (p=0.016). CONCLUSIONS: The rs652438 SNP alters MMP-12
      activity with the A allele being more active, which is associated with increased
      macrophage infiltration and emphysema in the lungs of patients with COPD. These
      findings further implicate MMP-12 and this SNP in COPD.

PMID- 21730351
TI  - Effect of urbanisation on asthma, allergy and airways inflammation in a
      developing country setting.
AB  - BACKGROUND: Asthma is a growing public health problem in developing countries.
      However, few studies have studied the role of urbanisation in this phenomenon. It
      was hypothesised that children living in a peri-urban setting in Peru have higher
      rates of asthma and allergy than rural counterparts. METHODS: 1441 adolescents
      aged 13-15 years were enrolled from two settings: a peri-urban shanty town in
      Lima (n = 725) and 23 rural villages in Tumbes (n = 716). Participants filled in
      questionnaires on asthma and allergy symptoms, environmental exposures and
      sociodemographics, and underwent spirometry, and exhaled nitric oxide (eNO) and
      allergy skin testing. Indoor particulate matter (PM) concentrations were measured
      in 170 households. RESULTS: Lima adolescents had higher rates of lifetime
      wheezing (22% vs 10%), current asthma symptoms (12% vs 3%) and physician
      diagnosed asthma (13% vs 2%; all p <0.001). Current rhinitis (23% vs 12%), eczema
      (12% vs 0.4%), atopy (56% vs 38%), personal history of cigarette smoking (7.4% vs
      1.3%) and mean indoor PM (31 vs 13 MUg/m(3)) were also higher in Lima (all p <
      0.001). The peri-urban environment of Lima was associated with a 2.6-fold greater
      odds (95% CI 1.3 to 5.3) of asthma in multivariable regression. Forced expiratory
      volumes were higher and FEV(1)/FVC (forced expiratory volume in 1 s/forced vital
      capacity) ratios were lower in Lima (all p < 0.001). Higher eNO values in Lima (p
      < 0.001) were attributable to higher rates of asthma and atopy. CONCLUSIONS: Peri
      urban adolescents had more asthma, atopy and airways inflammation and were
      exposed to more indoor pollution. The findings provide evidence of the risks
      posed to lung health by peri-urban environments in developing countries.

PMID- 21730352
TI  - Macrophage development from HSCs requires PU.1-coordinated microRNA expression.
AB  - The differentiation of HSCs into myeloid lineages requires the transcription
      factor PU.1. Whereas PU.1-dependent induction of myeloid-specific target genes
      has been intensively studied, negative regulation of stem cell or alternate
      lineage programs remains incompletely characterized. To test for such negative
      regulatory events, we searched for PU.1-controlled microRNAs (miRs) by expression
      profiling using a PU.1-inducible myeloid progenitor cell line model. We provide
      evidence that PU.1 directly controls expression of at least 4 of these miRs (miR
      146a, miR-342, miR-338, and miR-155) through temporally dynamic occupation of
      binding sites within regulatory chromatin regions adjacent to their genomic
      coding loci. Ectopic expression of the most robustly induced PU.1 target miR, miR
      146a, directed the selective differentiation of HSCs into functional peritoneal
      macrophages in mouse transplantation assays. In agreement with this observation,
      disruption of Dicer expression or specific antagonization of miR-146a function
      inhibited the formation of macrophages during early zebrafish (Danio rerio)
      development. In the present study, we describe a PU.1-orchestrated miR program
      that mediates key functions of PU.1 during myeloid differentiation.

PMID- 21730353
TI  - Prolonged self-renewal activity unmasks telomerase control of telomere
      homeostasis and function of mouse hematopoietic stem cells.
AB  - Strategies for expanding hematopoietic stem cells (HSCs) could have significant
      utility for transplantation-based therapies. However, deleterious consequences of
      such manipulations remain unknown. Here we examined the impact of HSC self
      renewal divisions in vitro and in vivo on their subsequent regenerative and
      continuing ability to sustain blood cell production in the absence of telomerase.
      HSC expansion in vitro was obtained using a NUP98-HOXA10hd transduction strategy
      and, in vivo, using a serial transplant protocol. We observed ~ 10kb telomere
      loss in leukocytes produced in secondary mice transplanted with HSCs regenerated
      in primary recipients of NUP98-HOXA10hd-transduced and in vitro-expanded Tert(-/
      ) HSCs 6 months before. The second generation leukocytes also showed elevated
      expression of gammaH2AX (relative to control) indicative of greater accumulating
      DNA damage. In contrast, significant telomere shortening was not detected in
      leukocytes produced from freshly isolated, serially transplanted wild-type (WT)
      or Tert(-/-) HSCs, suggesting that HSC replication posttransplant is not limited
      by telomere shortening in the mouse. These findings document a role of telomerase
      in telomere homeostasis, and in preserving HSC functional integrity on prolonged
      self-renewal stimulation.

PMID- 21730354
TI  - In vitro efficacy of forodesine and nelarabine (ara-G) in pediatric leukemia.
AB  - Forodesine and nelarabine (the pro-drug of ara-G) are 2 nucleoside analogues with
      promising anti-leukemic activity. To better understand which pediatric patients
      might benefit from forodesine or nelarabine (ara-G) therapy, we investigated the
      in vitro sensitivity to these drugs in 96 diagnostic pediatric leukemia patient
      samples and the mRNA expression levels of different enzymes involved in
      nucleoside metabolism. Forodesine and ara-G cytotoxicities were higher in T-cell
      acute lymphoblastic leukemia (T-ALL) samples than in B-cell precursor (BCP)-ALL
      and acute myeloid leukemia (AML) samples. Resistance to forodesine did not
      preclude ara-G sensitivity and vice versa, indicating that both drugs rely on
      different resistance mechanisms. Differences in sensitivity could be partly
      explained by significantly higher accumulation of intracellular dGTP in
      forodesine-sensitive samples compared with resistant samples, and higher mRNA
      levels of dGK but not dCK. The mRNA levels of the transporters ENT1 and ENT2 were
      higher in ara-G-sensitive than -resistant samples. We conclude that especially T
      ALL, but also BCP-ALL, pediatric patients may benefit from forodesine or
      nelarabine (ara-G) treatment.

PMID- 21730355
TI  - Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the
      resistance to nilotinib in chronic myeloid leukemia cells.
AB  - In this study, we have addressed how Lyn kinase signaling mediates nilotinib
      resistance by quantitative phospho-proteomics using Stable Isotope Labeling with
      Amino acid in Cell culture. We have found an increased tyrosine phosphorylation
      of 2 additional tyrosine kinases in nilotinib-resistant cells: the spleen
      tyrosine kinase Syk and the UFO family receptor tyrosine kinase Axl. This
      increased tyrosine phosphorylation involved an interaction of these tyrosine
      kinases with Lyn. Inhibition of Syk by the inhibitors R406 or BAY 61-3606 or by
      RNA interference restored the capacity of nilotinib to inhibit cell
      proliferation. Conversely, coexpression of Lyn and Syk were required to fully
      induce resistance to nilotinib in drug-sensitive cells. Surprisingly, the
      knockdown of Syk also strongly decreased tyrosine phosphorylation of Lyn and Axl,
      thus uncovering interplay between Syk and Lyn. We have shown the involvement of
      the adaptor protein CDCP-1 in resistance to nilotinib. Interestingly, the
      expression of Axl and CDCP1 were found increased both in a nilotinib-resistant
      cell line and in nilotinib-resistant CML patients. We conclude that an oncogenic
      signaling mediated by Lyn and Syk can bypass the need of Bcr-Abl in CML cells.
      Thus, targeting these kinases may be of therapeutic value to override imatinib or
      nilotinib resistance in CML.

PMID- 21730356
TI  - Pharmacologic inhibition of hepcidin expression reverses anemia of chronic
      inflammation in rats.
AB  - Anemia of chronic inflammation (ACI) is the most frequent anemia in hospitalized
      patients and is associated with significant morbidity. A major underlying
      mechanism of ACI is the retention of iron within cells of the reticuloendothelial
      system (RES), thus making the metal unavailable for efficient erythropoiesis.
      This reticuloendothelial iron sequestration is primarily mediated by excess
      levels of the iron regulatory peptide hepcidin down-regulating the functional
      expression of the only known cellular iron export protein ferroportin resulting
      in blockade of iron egress from these cells. Using a well-established rat model
      of ACI, we herein provide novel evidence for effective treatment of ACI by
      blocking endogenous hepcidin production using the small molecule dorsomorphin
      derivative LDN-193189 or the protein soluble hemojuvelin-Fc (HJV.Fc) to inhibit
      bone morphogenetic protein-Smad mediated signaling required for effective
      hepcidin transcription. Pharmacologic inhibition of hepcidin expression results
      in mobilization of iron from the RES, stimulation of erythropoiesis and
      correction of anemia. Thus, hepcidin lowering agents are a promising new class of
      pharmacologic drugs to effectively combat ACI.

PMID- 21730357
TI  - Starch biosynthesis in rice endosperm requires the presence of either starch
      synthase I or IIIa.
AB  - Starch synthase (SS) I and IIIa are the first and second largest components of
      total soluble SS activity, respectively, in developing japonica rice (Oryza
      sativa L.) endosperm. To elucidate the distinct and overlapping functions of
      these enzymes, double mutants were created by crossing the ss1 null mutant with
      the ss3a null mutant. In the F(2) generation, two opaque seed types were found to
      have either the ss1ss1/SS3ass3a or the SS1ss1/ss3ass3a genotype. Phenotypic
      analyses revealed lower SS activity in the endosperm of these lines than in those
      of the parent mutant lines since these seeds had different copies of SSI and
      SSIIIa genes in a heterozygous state. The endosperm of the two types of opaque
      seeds contained the unique starch with modified fine structure, round-shaped
      starch granules, high amylose content, and specific physicochemical properties.
      The seed weight was ~90% of that of the wild type. The amount of granule-bound
      starch synthase I (GBSSI) and the activity of ADP-glucose pyrophosphorylase
      (AGPase) were higher than in the wild type and parent mutant lines. The double
      recessive homozygous mutant prepared from both ss1 and ss3a null mutants was
      considered sterile, while the mutant produced by the leaky ss1 mutant*ss3a null
      mutant cross was fertile. This present study strongly suggests that at least SSI
      or SSIIIa is required for starch biosynthesis in rice endosperm.

PMID- 21730358
TI  - ZCN8 encodes a potential orthologue of Arabidopsis FT florigen that integrates
      both endogenous and photoperiod flowering signals in maize.
AB  - Higher plants use multiple perceptive measures to coordinate flowering time with
      environmental and endogenous cues. Physiological studies show that florigen is a
      mobile factor that transmits floral inductive signals from the leaf to the shoot
      apex. Arabidopsis FT protein is widely regarded as the archetype florigen found
      in diverse plant species, particularly in plants that use inductive photoperiods
      to flower. Recently, a large family of FT homologues in maize, the Zea
      CENTRORADIALIS (ZCN) genes, was described, suggesting that maize also contains FT
      related proteins that act as a florigen. The product of one member of this large
      family, ZCN8, has several attributes that make it a good candidate as a maize
      florigen. Mechanisms underlying the floral transition in maize are less well
      understood than those of other species, partly because flowering in temperate
      maize is dependent largely on endogenous signals. The maize indeterminate1 (id1)
      gene is an important regulator of maize autonomous flowering that acts in leaves
      to mediate the transmission or production of florigenic signals. This study finds
      that id1 acts upstream of ZCN8 to control its expression, suggesting a possible
      new link to flowering in day-neutral maize. Moreover, in teosinte, a tropical
      progenitor of maize that requires short-day photoperiods to induce flowering,
      ZCN8 is highly up-regulated in leaves under inductive photoperiods. Finally,
      vascular-specific expression of ZCN8 in Arabidopsis complements the ft-1
      mutation, demonstrating that leaf-specific expression of ZCN8 can induce
      flowering. These results suggest that ZCN8 may encode a florigen that integrates
      both endogenous and environmental signals in maize.

PMID- 21730359
TI  - Determination of tricresyl phosphate air contamination in aircraft.
AB  - Monitoring of tricresyl phosphate (TCP) contamination of cockpit air was
      undertaken in three types of military aircraft [fighter trainer (FT), fighter
      bomber (FB), and cargo transport (CT) aircraft]. The aircraft had a previous
      history of pilot complaints about cockpit air contamination suspected to
      originate from the engine bleed air supply through the entry of aircraft turbine
      engine oil (ATO) into the engine compressor. Air samples were collected in flight
      and on the ground during engine runs using sorbent tubes packed with Porapak Q
      and cellulose filters. A total of 78 air samples were analysed, from 46 different
      aircraft, and 48 samples were found to be below the limit of detection. Nine
      incidents of smoke/odour were identified during the study. The concentrations of
      toxic o-cresyl phosphate isomers were below the level of detection in all
      samples. The highest total TCP concentration was 51.3 MUg m(-3), while most were
      generally found to be <5 MUg m(-3) compared with the 8-h time-weighted average
      exposure limit of 100 MUg m(-3) for tri-o-cresyl phosphate. The highest
      concentrations were found at high engine power. Although TCP contamination of
      cabin/cockpit air has been the subject of much concern in aviation, quantitative
      data are sparse.

PMID- 21730360
TI  - Combined analysis of cortical (EEG) and nerve stump signals improves robotic hand
      control.
AB  - BACKGROUND: Interfacing an amputee's upper-extremity stump nerves to control a
      robotic hand requires training of the individual and algorithms to process
      interactions between cortical and peripheral signals. OBJECTIVE: To evaluate for
      the first time whether EEG-driven analysis of peripheral neural signals as an
      amputee practices could improve the classification of motor commands. METHODS:
      Four thin-film longitudinal intrafascicular electrodes (tf-LIFEs-4) were
      implanted in the median and ulnar nerves of the stump in the distal upper arm for
      4 weeks. Artificial intelligence classifiers were implemented to analyze LIFE
      signals recorded while the participant tried to perform 3 different hand and
      finger movements as pictures representing these tasks were randomly presented on
      a screen. In the final week, the participant was trained to perform the same
      movements with a robotic hand prosthesis through modulation of tf-LIFE-4 signals.
      To improve the classification performance, an event-related
      desynchronization/synchronization (ERD/ERS) procedure was applied to EEG data to
      identify the exact timing of each motor command. RESULTS: Real-time control of
      neural (motor) output was achieved by the participant. By focusing
      electroneurographic (ENG) signal analysis in an EEG-driven time window, movement
      classification performance improved. After training, the participant regained
      normal modulation of background rhythms for movement preparation (alpha/beta band
      desynchronization) in the sensorimotor area contralateral to the missing limb.
      Moreover, coherence analysis found a restored alpha band synchronization of
      Rolandic area with frontal and parietal ipsilateral regions, similar to that
      observed in the opposite hemisphere for movement of the intact hand. Of note,
      phantom limb pain (PLP) resolved for several months. CONCLUSIONS: Combining
      information from both cortical (EEG) and stump nerve (ENG) signals improved the
      classification performance compared with tf-LIFE signals processing alone;
      training led to cortical reorganization and mitigation of PLP.

PMID- 21730361
TI  - COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to
      M1 in ApcMin/+ mouse polyps.
AB  - Macrophages are a major component of tumor stroma. Tumor-associated macrophages
      (TAMs) show anti- (M1) or protumor (M2) functions depending on the cytokine
      milieu of the tumor microenvironment. Cyclooxygenase-2 (COX-2) is constitutively
      expressed in a variety of tumors including colorectal cancer. TAMs are known to
      be a major source of COX-2 in human and mice intestinal tumors. COX-2 inhibitor
      reduces the number and size of intestinal adenomas in familial adenomatous
      polyposis patients and Apc(Min/+) mice. Although COX-2 inhibitor is thought to
      regulate cancer-related inflammation, its effect on TAM phenotype remains
      unknown. Here, we examined the effects of COX-2 inhibition on TAM phenotype and
      cytokine expression both in vivo and in vitro. Firstly, the selective COX-2
      inhibitor celecoxib changed the TAM phenotype from M2 to M1, in proportion to the
      reduction in number of Apc(Min/+) mouse polyps. Concomitantly, the expression of
      M1-related cytokine interfron (IFN)-gamma was significantly upregulated by
      celecoxib, although the M2-related cytokines interleukin (IL)-4, IL-13 and IL-10
      were not significantly altered. Secondly, IFN-gamma treatment attenuated M2
      phenotype of mouse peritoneal macrophages and oriented them to M1 even in the
      presence of M2-polarizing cytokines such as IL-4, IL-13 and IL-10. Thus, our
      results suggest that COX-2 inhibition alters TAM phenotype in an IFN-gamma
      dependent manner and subsequently may reduce intestinal tumor progression.

PMID- 21730364
TI  - A note on erroneous ethnolinguistic affiliations in genetic studies of southern
      Africa.

PMID- 21730362
TI  - A prolonged and exaggerated wound response with elevated ODC activity mimics
      early tumor development.
AB  - Induction of ornithine decarboxylase (ODC), a key enzyme in polyamine
      biosynthesis, in ODC transgenic skin stimulates epidermal proliferation but not
      hyperplasia, activates underlying stromal cells and promotes skin tumorigenesis
      following a single subthreshold dose of a carcinogen. Because chronic wounds are
      a well-recognized risk factor for skin cancer, we investigated the response to a
      tissue remodeling event in normal skin that is abraded to remove only the
      epidermal layer in K6/ODC transgenic (follicular ODC expression) and in inducible
      ODCER transgenic mice (suprabasal ODC expression). When regenerative epidermal
      hyperplasia was resolved in normal littermates following abrasion, ODC transgenic
      mice exhibited progressive epidermal hyperplasia with formation of benign tumor
      growths and maintained an increased epidermal proliferation index and activation
      of translation-associated proteins at abrasion sites. The epidermal hyperplasia
      and tumor-like growth was accompanied by activation of underlying stromal cells
      and prolonged infiltration of inflammatory cells. Treatment with the anti
      inflammatory agent dexamethasone did not reduce the high proliferative index in
      the regenerated epidermis but dramatically reduced the epidermal hyperplasia and
      prevented the wound-induced tumor growths in abraded ODCER skin. Treatment with
      alpha-difluoromethylornithine, a specific inhibitor of ODC activity, normalized
      the wound response in transgenic mice and decreased wound-induced inflammation if
      administered from the time of abrasion but not if initiated 4 days following
      abrasion. These results suggest a role for polyamines in prolonging wound
      associated inflammation in addition to stimulating proliferation both of which
      are sufficient to sustain epidermal hyperplasia and benign tumor growth even in
      the absence of genetic damage.

PMID- 21730365
TI  - Human corpses as time capsules: new perspectives in the study of past mass
      disasters.
AB  - Looking at the corpses of past natural catastrophes can change completely the
      conception of how to study human bone remains. The recovery of the Herculaneum
      victims of the 79 AD Vesuvius eruption was an opportunity for me to adopt a new
      approach in the study of human skeletons and their context of discovery. During
      two years of field work, my first aim was to investigate the effects of
      pyroclastic surges on people and things. The conservation of skeletons and their
      replacement by fiberglass casts were also provided. This "field laboratory" has
      developed into a palaeoforensic investigation of the mass disaster caused by the
      79 AD natural event. Field and laboratory research, later extended to Pompeii
      plaster-cast corpses, were also carried out on the victims' remains, footprints,
      huts and objects found in the sites buried by the prehistoric "Avellino pumices"
      eruption (3780 +/- 100 BP). The new results obtained from the study of the causes
      of death of people hit by pyroclastic surges produced by past Vesuvius eruptions
      have proved essential in hazard evaluation in the Neapolitan district and other
      volcanic areas.

PMID- 21730366
TI  - Morphometric distances among five ethnic groups and evaluation of the secular
      trend in historical Libya.
AB  - This study analysed the variations, both in space and time, of 10 body dimensions
      and 2 anthropometric indexes of 745 adult males belonging to 5 ethnic groups of
      historical Lybia (el-Harabi, el-Baraghits, Marabtin, Oases inhabitants and
      Tuareg). The data were collected in the years 1928 and 1932 by Puccioni and
      Cipriani, two Italian anthropologists. The aim was to reconstruct the biological
      history of Libya at the time, and thus contribute to the ongoing debate on the
      evolution of the biological standard of living in developing Countries. The
      subjects were analysed by ethnicity and by 10-year age groups, after adjusting
      for age. The results of ANCOVA and Tukey's post-hoc test show that among and
      between groups there are statistical significant differences overall for armspan,
      height, head breadth, bizygomatic breadth, biiliac breadth/height and head
      breadth/head length indexes. By means of the cluster analysis, the el-Harabi, el
      Baraghits and Marabtin groups cluster together, whereas the Tuareg and Oases
      inhabitants cluster separately one from the other and both from the other three
      ethnic groups. Within-group variations are not very marked in all ethnicities. In
      general, there is the tendency, not statistically significant, to the reduction
      and/or stasis of body dimensions from the older to the younger, and the
      differences are greater among the older than the younger age classes. In
      conclusion, it can be argued that these groups, all different culturally and
      geographically, were following the same tendency of stasis of the secular trend
      of the body dimensions considered in this study, and such stasis persisted since,
      at least, the last twenty years of the 19th century, when the older were born.

PMID- 21730368
TI  - William H Prusoff dies at 90 - a renaissance man that revolutionized the
      treatment of herpesviruses and HIV.

PMID- 21730367
TI  - Involvement of Akt-1 and mTOR in sensitivity of breast cancer to targeted
      therapy.
AB  - Elucidating the response of breast cancer cells to chemotherapeutic and hormonal
      based drugs is clearly important as these are frequently used therapeutic
      approaches. A signaling pathway often involved in chemo- and hormonal-resistance
      is the Ras/PI3K/PTEN/Akt/mTOR cascades. In the studies presented in this report,
      we have examined the effects of constitutive activation of Akt on the sensitivity
      of MCF-7 breast cancer cells to chemotherapeutic- and hormonal-based drugs as
      well as mTOR inhibitors. MCF-7 cells which expressed a constitutively-activated
      Akt-1 gene [?Akt-1(CA)] were more resistant to doxorubicin, etoposide and 4-OH
      tamoxifen (4HT) than cells lacking ?Akt-1(CA). Cells which expressed ?Akt-1(CA)
      were hypersensitive to the mTOR inhibitor rapamycin. Furthermore, rapamycin
      lowered the IC50s for doxorubicin, etoposide and 4HT in the cells which expressed
      ?Akt-1(CA), demonstrating a potential improved method for treating certain breast
      cancers which have deregulated PI3K/PTEN/Akt/mTOR signaling. Understanding how
      breast cancers respond to chemo- and hormonal-based therapies and the mechanisms
      by which they can become drug resistant may enhance our ability to treat breast
      cancer. These results also document the potential importance of knowledge of the
      mutations present in certain cancers which may permit more effective therapies.

PMID- 21730369
TI  - Novel 1,2,4-triazole and purine acyclic cyclopropane nucleoside analogues:
      synthesis, antiviral and cytostatic activity evaluations.
AB  - BACKGROUND: Several published studies indicate that the acyclic guanine
      nucleoside analogues possessing bis(1,2-hydroxymethyl) substituted cyclopropane
      rings mimicking the sugar moiety are potent inhibitors of replication of several
      herpes viruses. METHODS: Established synthetic methods and antiviral and
      cytostatic activity assays were used for the evaluation of new 1,2,4-triazole and
      purine acyclic nucleoside analogues. RESULTS: The synthesis of new types of
      acyclic nucleoside analogues which incorporate 1,2,4-triazole or purine moiety
      bound via flexible methylenic spacer to the bis(1,2-hydroxymethyl) cyclopropane
      ring. None of the new compounds showed pronounced antiviral activities at
      subtoxic concentrations on a broad panel of DNA and RNA viruses. Evaluation of
      their affinity for herpes simplex type 1 (HSV-1) and varicella-zoster virus
      encoded thymidine kinases (VZV TK) also showed that none of the compounds was
      able to significantly inhibit 1 MUM deoxythymidine phosphorylation by HSV-1 and
      VZV TK at 500 MUM concentrations. The in vitro cytostatic activity evaluation
      results indicated a weak antiproliferative activity for all tested compounds.
      Only 6-pyrrolylpurine derivative bearing a carboxylic group substituted
      cyclopropane ring produced a rather slight inhibitory effect at higher micromolar
      concentrations on a breast carcinoma cell line (MCF-7) and no cytotoxic effect on
      human normal fibroblasts (WI 38). CONCLUSIONS: The lack of antiherpetic activity
      may be due to poor, if any, recognition of the compounds by virus-induced
      nucleoside kinases as an alternative substrate to become metabolically activated.

PMID- 21730370
TI  - Effects of TheraMax on influenza virus infections in cell culture and in mice.
AB  - BACKGROUND: Limited in vivo studies in the scientific literature suggest that
      components of green tea and elderberry may be beneficial in treating influenza
      virus infections. They are thought to act by blocking virus adsorption to cells.
      TheraMax((r)) is a proprietary medication administered by nasal spray that
      contains both green tea and elderberry extracts that was evaluated for antiviral
      activity. METHODS: TheraMax was tested by dilution in Madin-Darby canine kidney
      cell cultures in standard viral cytopathic effect (CPE) inhibition and virucidal
      assays against eight influenza A and B strains. It was also administered
      intranasally to mice to determine protective activity compared to oral
      oseltamivir against an influenza A/NWS/33 (H1N1) infection. RESULTS: In cell
      culture assays, TheraMax was found to inhibit viral CPE by 50% at a 1:20 dilution
      for seven of the eight virus strains, with no virucidal activity at 1:2 dilution.
      The undiluted product was administered to anaesthetized mice twice daily for 4
      days starting 2 h before or 12 h after infection. Alternatively, TheraMax and
      virus were combined for treatment and infection. Oseltamivir was given orally
      twice daily for 5 days at 10 mg/kg/day starting at -2 h. TheraMax (combined
      directly with virus) and oseltamivir each prevented death and curtailed weight
      loss during the infection, and improved lung haemorrhage scores on day 6.
      TheraMax starting at -2 h or 12 h significantly delayed death by >2 days and
      reduced lung haemorrhage scores, but most animals died. CONCLUSIONS: These
      combined results indicate that TheraMax delayed symptoms during animal
      infections, likely through blocking of virus adsorption.

PMID- 21730371
TI  - Epigallocatechin gallate inhibits the HIV reverse transcription step.
AB  - BACKGROUND: Epigallocatechin gallate (EGCG), the most abundant catechin in green
      tea, has been reported to inhibit HIV-1 replication prior to its integration into
      host DNA via various proposed mechanisms; however, the specific main target(s) of
      EGCG remain unclear. In this study, we investigated a number of these proposed
      detailed mechanism(s) using a cell-based model. METHODS: Multinuclear activation
      of galactosidase indicator assays were used for all experiments, including
      examination of the time of addition and the synergisms with a nucleoside reverse
      transcriptase inhibitor, 3'-azido-3'-deoxythymidine (AZT). RESULTS: The
      experiments revealed that EGCG suppressed both HIV-1(IIIB) and HIV-2(EHO)
      infection in HeLa-CD4-LTR-beta-gal cells, with relatively low 50% effective
      concentrations of 1.6 and 2.0 MUM, respectively. The inhibitory profile of EGCG
      generated using a time-of-addition assay was identical to that of a non
      nucleoside reverse transcriptase inhibitor (NNRTI), MKC-442. Furthermore,
      synergistic inhibition was observed in EGCG with AZT. CONCLUSIONS: Based on our
      findings, EGCG appears to act mainly as an allosteric reverse transcriptase
      inhibitor with mechanisms different from those of currently approved NNRTIs that
      directly interact with the NNRTI binding pocket. Thus, EGCG is a good candidate
      for use as an additional or supportive anti-HIV agent derived from natural
      plants.

PMID- 21730372
TI  - Highly parallel fabrication of nanopatterned surfaces with nanoscale orthogonal
      biofunctionalization imprint lithography.
AB  - Large areas of nanopatterns of specific chemical functionality are needed for
      biological experiments and biotechnological applications. We present nanoscale
      orthogonal biofunctionalization imprint lithography (NOBIL), a parallel top-down
      imprinting and lift-off technique based on step-and-flash imprint lithography
      (SFIL) that is able to create centimetre-scale areas of nanopatterns of two
      biochemical functionalities. A photoresist precursor is polymerized with a
      template in place, and the thin resist layer is etched to create an undercut for
      lift-off. Gold nano-areas on a silicon dioxide background are then independently
      functionalized using self-assembly that translates the nanopattern into a cell
      adhesive/cell-rejective functionality pattern. We demonstrate the technique by
      creating fibronectin areas down to a pattern size of 60 nm against a polyethylene
      glycol (PEG) background, and show initial results of cells stably seeded over an
      array of 1 mm(2) areas of controlled size and pitch.

PMID- 21730373
TI  - In situ observation of fluoride-ion-induced hydroxyapatite-collagen detachment on
      bone fracture surfaces by atomic force microscopy.
AB  - The topography of freshly fractured bovine and human bone surfaces was determined
      by the use of atomic force microscopy (AFM). Fracture surfaces from both kinds of
      samples exhibited complex landscapes formed by hydroxyapatite mineral platelets
      with lateral dimensions ranging from ~90 nm * 60 nm to ~20 nm * 20 nm. Novel AFM
      techniques were used to study these fracture surfaces during various chemical
      treatments. Significant topographical changes were observed following exposure to
      aqueous solutions of ethylenediaminetetraacetic acid (EDTA) or highly
      concentrated sodium fluoride (NaF). Both treatments resulted in the apparent loss
      of the hydroxyapatite mineral platelets on a timescale of a few seconds. Collagen
      fibrils situated beneath the overlying mineral platelets were clearly exposed and
      could be resolved with high spatial resolution in the acquired AFM images. Time
      dependent mass loss experiments revealed that the applied agents (NaF or EDTA)
      had very different resulting effects. Despite the fact that the two treatments
      exhibited nearly identical results following examination by AFM, bulk bone
      samples treated with EDTA exhibited a ~70% mass loss after 72 h, whereas for the
      NaF-treated samples, the mass loss was only of the order of ~10%. These results
      support those obtained from previous mechanical testing experiments, suggesting
      that enhanced formation of superficial fluoroapatite dramatically weakens the
      protein-hydroxyapatite interfaces. Additionally, we discovered that treatment
      with aqueous solutions of NaF resulted in the effective extraction of
      noncollagenous proteins from bone powder.

PMID- 21730374
TI  - MR imaging of Her-2/neu protein using magnetic nanoparticles.
AB  - The aim of this study was to assess whether Her-2/neu expressing tumour cells can
      be detected in vitro as well as in animal tumour models with magnetic resonance
      imaging at 1.5 T. Magnetic nanoparticles (with relaxivities R 1, R 2 of 3.7 +/-
      0.4 (mM s)(-1), 277 +/- 32 (mM s)(-1) at 21  degrees C, respectively) coupled to
      anti-Her-2/neu antibodies or gamma globulin IgG (high or non-affinity probe,
      respectively) were used. After incubation of Her-2/neu expressing cells (SKBR3)
      with high or non-affinity probes (20 min), values of R 1 = 0.34 +/- 0.02 (mM s)(
      1) and R 2 = 63.02 +/- 30 (mM s)(-1) were obtained. Electron microscopy and
      atomic absorption spectrometry examinations verified the presence of relatively
      high iron levels in cells incubated with the high affinity probe compared to
      controls. For in vivo MRI, high or non-affinity probes (~1.7 mg Fe/animal) were
      injected into the tail vein of mice (n = 16) bearing SKBR3 tumours. A distinct
      decrease in the normalized MR signal ratio between tumour and reference area
      (approximately -17 +/- 2%) after application of the high affinity probe was
      observed. In conclusion, in vivo detection of Her-2/neu expressing tumours is
      feasible in a clinical MR scanner by using immunoconjugated magnetic
      nanoparticles.

PMID- 21730375
TI  - Electrostatic deposition of graphene.
AB  - Loose graphene sheets, one to a few atomic layers thick, are often observed on
      freshly cleaved HOPG surfaces. A straightforward technique using electrostatic
      attraction is demonstrated to transfer these graphene sheets to a selected
      substrate. Sheets from one to 22 layers thick have been transferred by this
      method. One sheet after initial deposition is measured by atomic force microscopy
      to be only an atomic layer thick (~0.35 nm). A few weeks later, this height is
      seen to increase to ~0.8 nm. Raman spectroscopy of a single layer sheet shows the
      emergence of an intense D band which dramatically decreases as the number of
      layers in the sheet increase. The intense D band in monolayer graphene is
      attributed to the graphene conforming to the roughness of the substrate. The
      disruption of the C-C bonds within the single graphene layer could also
      contribute to this intense D band as evidenced by the emergence of a new band at
      1620 cm(-1).

PMID- 21730376
TI  - PTCDA molecules on an InSb(001) surface studied with atomic force microscopy.
AB  - PTCDA (3,4,9,10-perylene-tetracarboxylic-dianhydride) molecular structures
      assembled on an InSb(001) c(8 * 2) reconstructed surface have been studied using
      frequency modulated atomic force microscopy. The high-resolution imaging of the
      structures is possible through repulsive interactions, using the constant height
      scanning mode. During initial stages of growth the [110] diffusion channel
      dominates as indicated by formation of long PTCDA molecular chains parallel to
      the [110] crystallographic direction on the InSb surface. For a single monolayer
      coverage a wetting layer of PTCDA is formed. Finally it is shown that the
      PTCDA/InSb is a promising system for building molecular nanostructures by
      manipulation of single molecules with the AFM tip.

PMID- 21730377
TI  - Fabrication of functional nano-patterned surfaces by a combination of plasma
      processes and electron-beam lithography.
AB  - This work presents a method for the fabrication of well defined chemically active
      nano-patterned surfaces. Electron-beam lithography has been combined with plasma
      based processes in order to create sub-micron carboxylic functional areas over a
      non-bio-adhesive matrix. Characterization of the patterned surface by several
      surface analysis techniques reveals that this patterning technique is compatible
      with the plasma polymerization process in order to fabricate chemically active
      features with lateral size down to 300 nm. Moreover, experiments with a model
      protein (bovine serum albumin) on the patterned surfaces show preferential
      adhesion on the active region indicating the ability of this method for the
      design of biosensing platforms.

PMID- 21730378
TI  - Fabrication of self-sealed circular nano/microfluidic channels in glass
      substrates.
AB  - We realized self-sealing fluidics channels with circular cross-sections having
      diameters ranging between 30 and 2000 nm on a 200 mm glass wafer through CMOS
      compatible processes. Lateral voids were narrowed and sealed with non-conformal
      plasma enhanced chemical vapour deposition (PECVD) of phospho silicate glass
      (PSG) along silicon oxide trenches on silicon wafers. Leveraging on the reflow
      properties of PSG, circular profiled-channels were formed after undergoing high
      temperature annealing. These devices were subsequently transferred onto a
      borosilicate glass substrate through anodic bonding, and a fully transparent
      microfluidic device was achieved with the complete removal of the handle silicon
      substrate. The process offers a means of integrating electrochemical and optical
      sensing on the same platform, for biological research.

PMID- 21730379
TI  - Fabrication and in vitro biomineralization of bioactive glass (BG) nanofibres.
AB  - Bioactive glass nanofibres have excellent bioactivity and cell compatibility, and
      are regarded as a promising next-generation biomaterial in the bone-regeneration
      field. This paper is concentrated on the effect of electrospinning parameters on
      the diameter and morphology of bioactive glass nanofibres, and the process of in
      vitro biomineralization. In this work, sol-gel glass nanofibres with high
      bioactivity were prepared by electrospinning processing in the presence of
      poly(vinyl pyrrolidone) (PVP) and pluronic P123 (EO(20)-PO(70)-EO(20)) as chain
      entanglements. The influence of the polymer concentration, types of polymer and
      electric field strength on the fibre diameter was examined. The average diameter
      of these BG nanofibres could be controlled in the range from 85 to 400 nm. The
      addition of PVP resulted in sufficient chain entanglement and the formation of
      smooth BG nanofibres, and the addition of P123 led to a further decrease of the
      diameter with appropriate electric field strength, which held the balance between
      the electrostatic repulsive force and surface tension of the electrospinning
      solution. Furthermore, the early stage of in vitro biomineralization of the BG
      nanofibres in the simulated body fluid (SBF) was studied in this work. The
      behaviour of in vitro biomineralization of bioactive glass nanofibres was
      different to the conventional ones, and the structure of bioactive glasses
      contributed to the formation process of hydroxyapatite.

PMID- 21730380
TI  - Synthesis of gold and silver nanoparticles by electron irradiation at 5-15 keV
      energy.
AB  - Thin coatings (~10 um) made from a mixture of polyvinyl alcohol (PVA) and
      HAuCl(4) or PVA and AgNO(3) on quartz plates were irradiated with 5-15 keV
      electrons, at room temperature. The electron energy was varied from coating to
      coating in the range of 5-15 keV, but electron fluence was kept constant at
      ~10(15) e cm(-2). Samples were characterized by the UV-vis, XRD, SEM and TEM
      techniques. The plasmon absorption peaks at ~511 and ~442 nm confirmed the
      formation of gold and silver nanoparticles in the respective electron-irradiated
      coatings. The XRD, SEM and TEM measurements reveal that the average size of the
      particles could be tailored in the range of 130-50 nm for gold and from 150-40 nm
      for silver by varying the electron energy in the range of 5-15 keV. These
      particles of gold and silver embedded in the polymer could also be separated by
      dissolving the coatings in distilled water.

PMID- 21730381
TI  - Chemical vapour deposition of single walled carbon nanotubes freely suspended
      over nanotube supports.
AB  - Single walled carbon nanotubes (SWNTs) suspended above the substrate can be
      fabricated simply and rapidly by chemical vapour deposition growth over pre-grown
      multi-walled carbon nanotubes (MWNTs). SWNTs are suspended either on a randomly
      organized carbon nanotube network on an unpatterned substrate, or between
      organized pillars made from vertically aligned nanotube forests on a patterned
      substrate. All nanotubes are produced during a single growth run using a two step
      growth technique. This approach enables the fabrication of laterally suspended
      SWNT networks which are well suited for optical applications.

PMID- 21730382
TI  - Enhanced field emission from injector-like ZnO nanostructures with minimized
      screening effect.
AB  - Injector-like zinc oxide (ZnO) nanostructures have been synthesized on Si
      substrate by the vapour phase transport method. Samples with different areal
      densities were obtained by controlling the temperature. The field emission
      properties of the injector-like ZnO nanostructures showed a clear dependence on
      the areal density of the nanostructures, which is due to the screening effect.
      The samples with a needle length of 850 nm and an areal density of 1 * 10(8) cm(
      2) showed the lowest field emission turn-on field of 1.85 V um(-1) at a current
      density of 10 uA cm(-2), and the current density reaches 1 mA cm(-2) at an
      applied field of 4.7 V um(-1).

PMID- 21730383
TI  - One-step synthesis of titania nanoparticles from PS-P4VP diblock copolymer
      solution.
AB  - Polymeric films containing titania nanoparticles have potential as dielectric
      films for flexible electronic applications. For this purpose, the nanoparticles
      must be homogeneously distributed. Self-assembly is emerging as a neat, elegant
      method for fabricating such nanostructured hybrid materials with well-distributed
      nanoparticles. In this work, we report a micellar solution approach for the
      assembly of copolymer-titanium precursor nanostructures in which titania
      nanoparticles were synthesized. The ratio of the amount of titanium precursor,
      titanium isopropoxide, to the blocks forming the micellar core, poly(4
      vinylpyridine), was found to play a key role in controlling film morphology. A
      sphere-to-ribbon transition was observed when the amount of titanium isopropoxide
      was increased. The thin film morphology can be tuned using the precursor
      copolymer interaction rather than just the polymer-polymer interaction or the
      polymer-solution interaction. This method provides yet another way to control the
      morphology of nanostructures.

PMID- 21730384
TI  - Controlled synthesis of rod-like LiVMoO(6) nanocrystals for application in
      lithium-ion batteries.
AB  - This paper reports a newly developed method for the shape and size control of
      transition metal composite oxides, such as LiVMoO(6), to obtain significantly
      enhanced electrode properties for lithium-ion batteries. Rod-like LiVMoO(6)
      nanocrystals were synthesized through a designed route of partial reduction, self
      assembly and re-oxidation. V(5+) and Mo(6+) ions were used with low-grade
      starting materials to get a mixed valence of V and Mo. It is believed that ion
      pairs of V(5+)/V(4+) or Mo(6+)/Mo(5+) in the resultant mixture play an important
      role in the formation of a template precursor by self-assembly during a
      rheological phase reaction, although further explanation is required. The
      electrochemical performance of the LiVMoO(6) obtained has been much improved due
      to the increased crystallinity and reduced particle size of this material. 176 mA
      h g(-1) and 166 mA h g(-1) capacity was delivered in the initial discharge with a
      reversible capacity retention of 94.8% and 95.3% after 100 cycles in the range of
      3.6-1.80 V versus metallic Li at 1 and 3 C current rate, respectively.

PMID- 21730385
TI  - Facile synthesis of polymer-enveloped ultrasmall superparamagnetic iron oxide for
      magnetic resonance imaging.
AB  - Ultrasmall superparamagnetic iron oxide (USPIO) with synthetic polymer, based on
      magnetite core, was synthesized via facile photochemical in situ polymerization.
      A possible mechanism of photochemical in situ polymerization was proposed. The
      obtained polymer-enveloped UPSIO was characterized by transmission electron
      microscopy (TEM), photo-correlation spectroscopy (PCS), Fourier transform
      infrared spectroscopy (FT-IR), thermogravimetric (TG) analysis and vibrating
      sampling magnetometer (VSM) measurement. Properties such as ultrasmall particle
      size, hydrophilicity, strong magnetization and surface characteristics, which are
      desirable for magnetic resonance imaging (MRI) contrast agents, were evaluated in
      detail. The resultant USPIO-based MRI contrast agent holds considerable promise
      in molecular MR tracking, MR immune imaging, cell tracking and targeted
      intracellular hyperthermia, etc.

PMID- 21730386
TI  - Nanoindentation characteristics of clamped freestanding Cu membranes.
AB  - This research employed instrumented nanoindentation to address the issue of
      bending to stretching-induced deformation of clamped freestanding Cu membranes.
      The experimental results show that indentation-induced plastic deformation only
      comes into effect at the centre and the indented edge of the Cu membrane when the
      indenter is applied, while the other locations remain undamaged. A step-by-step
      evolution was presumed for the time histories of the bending to stretching
      induced deformation and for the timing of the significant change in slope of the
      load-deflection curve. Deformation was deliberately introduced at the transition
      from the single-point bending indentation to the surface stretching indentation
      at the impact location touched with the indenter. Good elastic recovery was found
      at locations away from the indenter. A similar finding can be arrived at by means
      of finite element analysis.

PMID- 21730387
TI  - Non-equilibrium all-atom molecular dynamics simulations of free and tethered DNA
      molecules in nanochannel shear flows.
AB  - In order to gain insight into the mechanical and dynamical behaviour of free and
      tethered short chains of ss/ds DNA molecules in flow, and in parallel to
      investigate the properties of long chain molecules in flow fields, we have
      developed a series of quantum and molecular methods to extend the well developed
      equilibrium software CHARMM to handle non-equilibrium dynamics. These methods
      have been applied to cases of DNA molecules in shear flows in nanochannels.
      Biomolecules, both free and wall-tethered, have been simulated in the all-atom
      style in solvent-filled nanochannels. The new methods were demonstrated by
      carrying out NEMD simulations of free single-stranded DNA (ssDNA) molecules of 21
      bases as well as double-stranded DNA (dsDNA) molecules of 21 base pairs tethered
      on gold surfaces in an ionic water shear flow. The tethering of the linker
      molecule (6-mercapto-1-hexanol) to perfect Au(111) surfaces was parametrized
      based on density functional theory (DFT) calculations. Force field parameters
      were incorporated into the CHARMM database. Gold surfaces are simulated in a
      Lennard-Jones style model that was fitted to the Morse potential model of bulk
      gold. The bonding force of attachment of the DNA molecules to the gold substrate
      linker molecule was computed to be up to a few nN when the DNA molecules are
      fully stretched at high shear rates. For the first time, we calculated the
      relaxation time of DNA molecules in picoseconds (ps) and the hydrodynamic force
      up to a few nanoNewtons (nN) per base pair in a nanochannel flow. The velocity
      profiles in the solvent due to the presence of the tethered DNA molecules were
      found to be nonlinear only at high shear flow rates. Free ssDNA molecules in a
      shear flow were observed to behave differently from each other depending upon
      their initial orientation in the flow field. Both free and tethered DNA molecules
      are clearly observed to be stretching, rotating and relaxing. Methods developed
      in this initial work can be incorporated into multiscale simulations including
      quantum mechanical, molecular and the microfluidic continuum regimes. The results
      may also be useful in extending existing macroscopic empirical models of DNA
      response dynamics in shear flows.

PMID- 21730388
TI  - Why nano-oxidation with carbon nanotube probes is so stable: I. Linkage between
      hydrophobicity and stability.
AB  - Carbon nanotube (CNT) probes enhance the stability of the nano-oxidation process
      under dynamic-mode operation. In this paper we investigate how the hydrophobic
      nature of the CNT allows oxide nanostructures to be fabricated with constant
      aspect ratio over a wide range of relative humidity values. In particular, we
      characterize oxide growth by measuring both the integrated ionic current and
      volume expansion. Behaviour of different CNT probes was compared to assess
      individual stability and performance under identical voltage and humidity
      conditions. While much remains to be established about the relationship between
      exposure conditions and dynamic-mode parameters on nanoscale oxide fabrication,
      hydrophobicity is a key factor in the improved reliability of CNT probes over
      conventional ones.

PMID- 21730389
TI  - Why nano-oxidation with carbon nanotube probes is so stable: II. Bending
      behaviour of CNT probes during nano-oxidation.
AB  - Part I demonstrated that nano-oxidation in the dynamic-force mode was enhanced by
      the use of conductive carbon nanotube (CNT) probes. Fabrication of oxide
      nanostructures using CNT probes benefited not only from the smaller tip apex
      compared to conventional probes but from improved operational stability over a
      wide range of exposure conditions primarily due to the hydrophobic nature of the
      CNT. Here we investigate the bending response of CNT probes to electrostatic and
      meniscus forces during nano-oxidation. We conclude that bending of the CNT
      introduces an additional cushion in the combined cantilever-probe deflection
      system, thus improving overall stability of the tip-sample junction during nano
      oxidation.

PMID- 21730390
TI  - Nanosecond laser pulse-induced electron emission from multiwall carbon nanotube
      film.
AB  - Electron emission from multiwall carbon nanotube film induced by the irradiation
      of the second, third and fourth harmonics of a Q-switched Nd:YAG laser was
      studied as a function of applied voltage and irradiation energy. The experimental
      result at 266 nm showed a one-photon field-assisted photoemission mechanism at
      low laser energy and a thermal contribution at higher energy. At 355 and 532 nm
      wavelengths, the emission seems to be due to thermal assisted field emission.

PMID- 21730391
TI  - Effect of inorganic-organic composite coating on the dispersion of silicon
      carbide nanoparticles in non-aqueous medium.
AB  - In order to disperse silicon carbide (SiC) nanoparticles homogeneously in a non
      aqueous medium, the surface of SiC nanoparticles needs to be modified via surface
      organic functionalization. A method of SiC nanoparticle surface modification by
      grafting of polyacetals via inorganic-organic composite coating was developed.
      The resulting graft percentage of up to 10.5% was much higher than that of direct
      grafting. The inorganic-organic composite coating on a SiC nanoparticle surface
      led to an almost complete decomposition of the secondary structure of the
      agglomerates and the formation of the primary structure. Dispersibility of the
      modified version was studied by using a transmission electron microscope (TEM)
      and size distribution analyser. The sedimentation experiments showed that the
      coated SiC nanoparticles exhibited good suspension stability in butanone. The
      composition of the inorganic-organic composite coating on the SiC nanoparticles
      was investigated by energy dispersive x-ray analyses (EDX), hydrogen nuclear
      magnetic resonance ((1)H NMR) and Fourier-transformed infrared spectroscopy (FT
      IR). This work provides a novel concept of surface grafting modification for non
      oxide nanoparticles to improve their dispersibility in non-aqueous medium.

PMID- 21730392
TI  - A single electric relaxation time in Ba(1-x)Sr(x)TiO(3) nanoparticles at low
      temperatures.
AB  - It is shown that the dielectric response of Ba(0.77)Sr(0.23)TiO(3) nanoparticles
      at temperatures below 200 K has a frequency and temperature dependence in
      agreement with the Debye theory with a single relaxation time, which exhibits the
      Arrhenius law. By contrast, at temperatures above 210 K the dielectric response
      exhibits a broad range of relaxation times characteristic of relaxor
      ferroelectrics. We suggest that the single relaxation time at low temperature
      originates from a frustration effect, in analogy with frustrated
      antiferromagnetism.

PMID- 21730393
TI  - Mechanical elasticity of vapour-liquid-solid grown GaN nanowires.
AB  - Mechanical elasticity of hexagonal wurtzite GaN nanowires with hexagonal cross
      sections grown through a vapour-liquid-solid (VLS) method was investigated using
      a three-point bending method with a digital-pulsed force mode (DPFM) atomic force
      microscope (AFM). In a diameter range of 57-135 nm, bending deflection and
      effective stiffness, or spring constant, profiles were recorded over the entire
      length of end-supported GaN nanowires and compared to the classic elastic beam
      models. Profiles reveal that the bending behaviour of the smallest nanowire (57.0
      nm in diameter) is as a fixed beam, while larger nanowires (89.3-135.0 nm in
      diameter) all show simple-beam boundary conditions. Diameter dependence on the
      stiffness and elastic modulus are observed for these GaN nanowires. The GaN
      nanowire of 57.0 nm diameter displays the lowest stiffness (0.98 N m(-1)) and the
      highest elastic modulus (400 +/- 15 GPa). But with increasing diameter, elastic
      modulus decreases, while stiffness increases. Elastic moduli for most tested
      nanowires range from 218 to 317 GPa, which approaches or meets the literature
      values for bulk single crystal and GaN nanowires with triangular cross sections
      from other investigators. The present results together with further tests on
      plastic and fracture processes will provide fundamental information for the
      development of GaN nanowire devices.

PMID- 21730394
TI  - Preferred growth orientation of metallic fcc nanowires under direct and
      alternating electrodeposition conditions.
AB  - Gold and copper nanowires were generated through electrochemical deposition into
      nanoporous polymeric templates. Depending on the growth conditions, such wires
      exhibited a distinct textured structure as evidenced by x-ray diffraction. The
      preferred growth orientation is explained by applying the broken-bond model in
      combination with surface-energy anisotropy and energy minimization. During the
      growth process, the aspect ratio of the cylindrical nanowire and thus the area of
      the mantle surface and its contribution to the total surface energy increase.
      Under direct current deposition conditions, [Formula: see text] textured metallic
      fcc nanowires represent the configuration of lowest surface energy at aspect
      ratios above 1. Under alternating current deposition conditions, {110} nanowire
      base surfaces vanish due to their high surface energy, leading to successive
      development of a [Formula: see text] texture as the configuration of lowest
      energy at aspect ratios above 5.

PMID- 21730395
TI  - Synthesis of indium nanoclusters and formation of thin film contacts on plastic
      substrates for organic and flexible electronics applications.
AB  - In this work, we described the processes of synthesizing free-standing indium
      nanoclusters using inverse micelles and microemulsions as well as synthesizing
      organic-encapsulated indium nanoclusters using alkanethiols as the organic
      encapsulants. The synthesized organic-encapsulated indium nanoclusters have
      demonstrated the feasibilities to be used as plastic compatible soft metal
      contacts for emerging organic devices. The homogeneously distributed indium
      nanoclusters with sizes of 10-30 nm have been fabricated on a few different
      plastic substrates. By changing the alkanethiol carbon chain length and the sizes
      of the indium nanoclusters, the annealing temperature required to form low
      resistance indium thin film conductors has been reduced to 80-100  degrees C,
      which is acceptable for a variety of organic thin films.

PMID- 21730396
TI  - High performance short period superlattice digital alloy InSb/Ga(x)In(1-x)Sb
      laser emitting at 1.9 um.
AB  - For the first time, lasers with short period superlattice based quantum wells
      have successfully been fabricated and characterized on the (AlGaIn)(AsSb)
      material system. These new quantum wells are composed of alternating
      InSb/Ga(x)In(1-x)Sb layers with submonolayer thickness. Distributed-feedback
      lasers fabricated from the epitaxial layers emit in the wavelength range around
      1.9 um. Side mode suppression ratios over 35 dB and very low threshold currents
      of 23 mA were realized. The laser emission wavelength can be varied from 1.844 to
      1.902 um using grating periods between 255.0 and 263.8 nm.

PMID- 21730397
TI  - Comparing the growth of PVD silver nanoparticles on ultra thin fluorocarbon
      plasma polymer films and self-assembled fluoroalkyl silane monolayers.
AB  - Adsorbed silver nanoparticles were prepared by means of electron beam evaporation
      of silver on ultra thin Si-supported heptadecafluoro-1-decene plasma polymer
      films and self-assembled heptadecafluorodecyl-trimethoxysilane monolayers. The
      morphology of the silver nanoparticles, characterized by their size, size
      distribution, shape and interparticle separation, was observed to depend on the
      type, chemical composition and surface energy of the sub-layer as well as the
      amount of silver deposited. Field emission-scanning electron microscopy was used
      to study the change in the morphology of the silver nanoparticles as a function
      of the preparation parameters. The silver nanoparticles on the ultra thin plasma
      polymer films demonstrated a much smaller and narrower size distribution due to
      the cross-linking within the film, which more effectively hinders the penetration
      of silver through the film in comparison to the self-assembled monolayers.
      Moreover, the optical properties of the resulting silver nanoparticles on the
      ultra thin fluorocarbon plasma polymers and their correlation to size and size
      distribution were investigated by spectroscopic ellipsometry in the wavelength
      range between 300 and 800 nm.

PMID- 21730398
TI  - Effect of the growth mode on the two- to three-dimensional transition of InAs
      grown on vicinal GaAs(001) substrates.
AB  - Some differences were observed between conventional molecular-beam epitaxy (MBE)
      and mobility enhanced epitaxy (MEE) of InAs on a vicinal GaAs(001) substrate in
      the variation of the number density N of the InAs islands, with additional InAs
      coverage (theta-theta(c)) after the critical InAs coverage theta(c) during the
      two- to three-dimensional (2D-3D) transition. For MBE the variation was
      consistent with the power law N(theta)~(theta-theta(c))(alpha); while for MEE,
      the linear relation [Formula: see text] was observed. The difference is discussed
      in terms of the randomness in the nucleation of the InAs islands.

PMID- 21730399
TI  - Rapid fabrication of 2D and 3D photonic crystals and their inversed structures.
AB  - In this paper a new technique is proposed for the fabrication of two-dimensional
      (2D) and three-dimensional (3D) photonic crystals using monodisperse polystyrene
      microspheres as the templates. In addition, the approaches toward the creation of
      their corresponding inversed structures are described. The inversed structures
      were prepared by subjecting an introduced silica source to a sol-gel process;
      programmed heating was then performed to remove the template without spoiling the
      inversed structures. Utilizing these approaches, 2D and 3D photonic crystals and
      their highly ordered inversed hexagonal multilayer or monolayer structures were
      obtained on the substrate.

PMID- 21730400
TI  - Selective binding of dye molecules and CdSe nanocrystals on nanostructures
      generated by AFM lithography of silicon surfaces.
AB  - Anchoring optically active molecules or semiconductor nanocrystals on
      nanostructured surfaces is one of the first steps for building complex structures
      with variable properties and functions. Electrostatic interactions have been used
      for selective binding of cationic molecular species on lithographically generated
      and negatively charged nanostructures. Semiconductor nanocrystals, covered by
      amphiphilic molecules, have been bound via hydrophobic interactions. Selective
      binding of cationic Rhodamin 6G molecules to freshly prepared silicon oxide
      nanostructures as well as the CdSe/ZnS nanocrystals to the surrounding
      hydrophobic alkyl monolayer could be identified both by optical methods and by
      atomic force microscopy. The adsorption of CdSe/ZnS nanoparticles was accompanied
      by self-organization phenomena of the surfactant tri octyl phosphine oxide
      (TOPO).

PMID- 21730401
TI  - Level set approach for the simulation of focused ion beam processing on the
      micro/nano scale.
AB  - The level set method, introduced by Osher and Sethian (1988 J. Comput. Phys. 79
      12-49), has recently become popular in the simulation of etching, deposition and
      photolithography processes in semiconductor manufacturing, as it is a highly
      robust and accurate computational technique for tracking moving interfaces. In
      this paper, the level set approach is applied to focused ion beam fabrication,
      allowing for the first time the simulation of targets with sub-regions that
      change their connectivity during processing. It is implemented in the code
      AMADEUS-level set (advanced modelling and design environment for sputter
      processes), which is capable of simulating surface topography changes in two
      dimensions taking re-deposition fluxes into account. We present two examples of
      comparisons between simulation and experiment that demonstrate the predictive
      capability of the code.

PMID- 21730402
TI  - A nanoscale three-dimensional Monte Carlo simulation of electron-beam-induced
      deposition with gas dynamics.
AB  - A computer simulation was developed to simulate electron-beam-induced deposition
      (EBID). Simulated growth produced high-aspect-ratio, nanoscale pillar structures
      by simulating a stationary Gaussian electron beam. The simulator stores in memory
      the spatial and temporal coordinates of deposited atoms in addition to the type
      of electron, either primary (PE), back-scattered (BSE), or secondary (SE), that
      induced its deposition. The results provided in this paper apply to tungsten
      pillar growth by EBID on a tungsten substrate from WF(6) precursor, although the
      simulation may be applied to any substrate-precursor set. The details of the
      simulation are described including the Monte Carlo electron-solid interaction
      simulation used to generate scattered electron trajectories and SE generation,
      the probability of molecular dissociation of the precursor gas when an electron
      traverses the surface, and the gas dynamics which control the surface coverage of
      the WF(6) precursor on the substrate and pillar surface. In this paper, three
      specific studies are compared: the effects of beam energy, mass transport versus
      reaction-rate-limited growth, and the effects of surface diffusion on the EBID
      process.

PMID- 21730403
TI  - Formation of various metal nanostructures with thermal annealing to control the
      effective coupling energy between a surface plasmon and an InGaN/GaN quantum
      well.
AB  - We demonstrate the variations of the photoluminescence (PL) spectral peak
      position and intensity through the surface plasmon (SP) coupling with an
      InGaN/GaN quantum well (QW) by forming Ag nanostructures of different scale sizes
      on the QW structure with thermal annealing. By transferring an Ag thin film into
      a nanoisland structure, we can not only enhance the PL intensity, but also adjust
      the SP dispersion relation and hence red-shift the effective QW emission
      wavelength. Such an emission spectrum control can be realized by initially
      coating Ag films of different thicknesses. Although the screening process of the
      quantum-confined Stark effect, which can result in PL spectrum blue-shift and
      intensity enhancement, also contributes to the variations of the emission
      behaviour, it is found that the SP-QW coupling process dominates in the observed
      phenomena.

PMID- 21730404
TI  - Electronic and atomic shell structure in aluminium nanowires.
AB  - We report experiments on aluminium nanowires in ultra-high vacuum at room
      temperature that reveal a periodic spectrum of exceptionally stable structures.
      Two 'magic' series of stable structures are observed: at low conductance, the
      formation of stable nanowires is governed by electronic shell effects whereas for
      larger contacts atomic packing dominates. The crossover between the two regimes
      is found to be smooth. A detailed comparison of the experimental results to a
      theoretical stability analysis indicates that, while the main features of the
      observed electron-shell structure are similar to those of alkali and noble
      metals, a sequence of extremely stable wires plays a unique role in aluminium.
      This series appears isolated in conductance histograms and can be attributed to
      'superdeformed' non-axisymmetric nanowires.

PMID- 21730405
TI  - CdSe quantum dot formation: alternative paths to relaxation of a strained CdSe
      layer and influence of the capping conditions.
AB  - CdSe/ZnSe quantum dot formation is investigated by studying different steps of
      the growth. To precisely control the critical thickness of CdSe grown on a ZnSe
      buffer layer, the CdSe self-regulated growth rate in atomic layer epitaxy growth
      mode is determined by reflection high-energy electron diffraction (RHEED)
      measurements for a temperature range between 180 and 280  degrees C. Then, the
      two-dimensional-three-dimensional (2D-3D) transition of a strained CdSe layer on
      (001)-ZnSe induced by the use of amorphous selenium is studied. The formation of
      CdSe islands is found when 3 monolayers (ML) of CdSe are deposited. When only 2.5
      ML of CdSe are deposited, another relaxation mechanism is observed, leading to
      the appearance of strong undulations on the surface. We also studied the
      evolution of the surface morphology when 2.7 ML are deposited, to study the
      boundary between those two phenomena. The influence of capping on quantum dot
      morphology is investigated. It is found that cadmium is redistributed within the
      layer during capping. Our results show that the cadmium distribution after
      capping depends on the capping temperature and on the strain of the CdSe layer.
      Cadmium incorporation after capping is also studied. It is found that the amount
      of incorporated cadmium depends on the strain of the CdSe layer before capping.

PMID- 21730406
TI  - Ultrahigh-current field emission from sandwich-grown well-aligned uniform multi
      walled carbon nanotube arrays with high adherence strength.
AB  - We describe a new method to grow multi-walled carbon nanotube (MWCNT) arrays,
      which enable very high and stable macroscopic emission current density of 3.55 A
      cm(-2) along with a scalable total emission current of more than 710 mA. A
      sandwich-growth technology was employed to synthesize vertically well-aligned
      MWCNT arrays in large areas and patterned uniformly by using microwave plasma
      chemical vapour deposition. A thick nickel layer was inserted between the silicon
      substrate and catalyst layer to achieve good adhesion between the MWCNTs and the
      substrate. Scanning electron microscope and transmission electron microscope
      investigations showed that well-structured, vertically aligned and uniform MWCNTs
      with perfect crystal lattices had been grown on lithographically predetermined
      sites. The root ends of MWCNTs adhered firmly to the nickel layer, establishing
      high electrical and thermal conductance of the MWCNTs to the substrate. This
      feature largely explains the large and stable emission current density of the
      MWCNT arrays.

PMID- 21730407
TI  - Ag nanoparticle effects on the thermoluminescent properties of monoclinic ZrO(2)
      exposed to ultraviolet and gamma radiation.
AB  - The goal of this work was to analyse ZrO(2) in the pure state and when doped with
      Ag nanoparticles, by electron microscopy, x-ray diffraction and
      thermoluminescence methods. According to the results obtained, Ag nanoparticles
      did not modify the morphology or the crystalline structure of the ZrO(2). The
      thermoluminescent (TL) response of pure ZrO(2) showed two peaks, one at 334 K and
      the other at 417 K, when it was exposed to ultraviolet (UV) radiation, and at 342
      and 397 K when gamma radiation was used. For ZrO(2) impregnated with Ag
      nanoparticles a diminished TL intensity due to nanoparticle shielding was
      observed, but the glow curve shape was similar. However, when Ag nanoparticles
      were added during the ZrO(2) synthesis, a shift of the TL peaks towards higher
      temperature values with reference to pure ZrO(2) was observed. A linear
      dependence of the integrated TL signal as a function of the irradiation dose was
      observed in all analysed samples. It was possible to determine some kinetic
      parameters, such as activation energy, kinetic order and frequency factor, using
      the sequential quadratic programming glow curve deconvolution; it was found that
      these values are highly dependent on the type of radiation used. Ag nanoparticles
      present in ZrO(2) also modified the kinetic parameters, mainly when they were
      added during the synthesis of ZrO(2). Our results reinforce the possibilities of
      using pure and doped ZrO(2) as an appropriate dosimetric material in radiation
      physics.

PMID- 21730408
TI  - Gold nanoparticles bound on microgel particles and their application as an enzyme
      support.
AB  - Submicron-sized poly(N-isopropyl acrylamide)/polyethyleneimine core-shell
      microgels were prepared in aqueous media by using tert-butyl hydroperoxide (TBHP)
      as an initiator, and then the gold nanoparticles (~8 nm) were formed on the
      surface of the microgels. The amino groups on the polyethyleneimine (PEI) chains
      act as the binder for the assembly of the gold nanoparticles/microgel complex. In
      aqueous media the microgels are highly stable with the gold nanoparticles on
      their extended PEI chains, and this multi-scale nanoparticle complex can be
      recovered from water and redispersed in water. The nanogold/microgel particles
      were conjugated with the enzymes horseradish peroxidase (HRP) and urease. It is
      found that under identical assay conditions the enzyme/nanogold/microgel systems
      exhibit enhanced biocatalytic activity over free enzymes in solution, especially
      at lower enzyme concentrations. In addition, compared to free HRP, the
      HRP/nanogold/microgel systems show higher activity at varied pHs and
      temperatures, as well as higher storage stability. Thus the novel
      nanogold/microgel particles can serve as an excellent support for enzymes.

PMID- 21730409
TI  - Cluster-assembled Tb-Fe nanostructured films produced by low energy cluster beam
      deposition.
AB  - Cluster-assembled Tb-Fe nanostructured films were prepared by the low energy
      cluster beam deposition method. The microstructure, magnetization and
      magnetostriction were investigated for the films. It is shown that the film is
      assembled by monodisperse spherical nanoparticles with average diameter of ~30 nm
      which are distributed uniformly. The cluster-assembled Tb-Fe nanostructured films
      exhibit good magnetization and possess giant magnetostriction with saturation
      value of ~1060 * 10(-6), much higher than that of the common Tb-Fe films. The
      origin of good magnetization and giant magnetostriction for the cluster-assembled
      Tb-Fe nanostructured film was discussed. The present work opens a new avenue to
      produce the nanostructured magnetostrictive alloy in application of a nano
      electro-mechanical system.

PMID- 21730410
TI  - Optical characterization of alignment and effective refractive index in carbon
      nanotube films.
AB  - We have characterized the thickness and effective refractive index of carbon
      nanotube forests by fitting reflectance measurements in the visible and near
      infrared ranges. The measurements were performed with polarized light. An
      effective medium layer consisting of a mixture of graphite and air was used to
      simulate the nanotube film. The proposed model accurately described the behaviour
      of the reflected s-polarized component (Rs), which allowed for the precise
      determination of the thickness and porosity of the films, in very good agreement
      with SEM measurements of film thickness. The p-polarized component (Rp), on the
      other hand, could not be described in terms of the developed model. In badly
      aligned samples, where there is a mixture of Rs and Rp behaviour, the model fails
      to fit the Rs component as well. This effect can therefore be taken as an
      indirect indication of lack of alignment in the samples.

PMID- 21730411
TI  - Enhanced resonance energy transfer from PVK to MEH-PPV in nanoparticles.
AB  - Organic semiconductor nanoparticles were prepared from poly(N-vinylcarbazole)
      (PVK), poly(2-methoxy-5-(2(')-ethyl-hexyloxy)-p-phenylene vinylene) (MEH-PPV) and
      their blend solution via a reprecipitation method, respectively. A wide
      photoluminescence band centred at 430 nm has been found in the PVK nanoparticles,
      which is obviously red-shifted by comparison with the PVK film. The red-shifted
      emission from the PVK nanoparticles has a good spectral superposition with the
      absorption of the MEH-PPV nanoparticles. However, the spectral superposition is
      very poor between the two polymers in the composite films. The markedly enhanced
      emission from MEH-PPV is experimentally observed in the composite polymer
      nanoparticles and attributed to Forster energy transfer from PVK to MEH-PPV for
      excitation at the absorption maximum of PVK.

PMID- 21730412
TI  - A two-colour heterojunction unipolar nanowire light-emitting diode by tunnel
      injection.
AB  - We present a systematic study of the current-voltage characteristics and
      electroluminescence of gallium nitride (GaN) nanowire on silicon (Si) substrate
      heterostructures where both semiconductors are n-type. A novel feature of this
      device is that by reversing the polarity of the applied voltage the luminescence
      can be selectively obtained from either the nanowire or the substrate. For one
      polarity of the applied voltage, ultraviolet (and visible) light is generated in
      the GaN nanowire, while for the opposite polarity infrared light is emitted from
      the Si substrate. We propose a model, which explains the key features of the
      data, based on electron tunnelling from the valence band of one semiconductor
      into the conduction band of the other semiconductor. For example, for one
      polarity of the applied voltage, given a sufficient potential energy difference
      between the two semiconductors, electrons can tunnel from the valence band of GaN
      into the Si conduction band. This process results in the creation of holes in
      GaN, which can recombine with conduction band electrons generating GaN band-to
      band luminescence. A similar process applies under the opposite polarity for Si
      light emission. This device structure affords an additional experimental handle
      to the study of electroluminescence in single nanowires and, furthermore, could
      be used as a novel approach to two-colour light-emitting devices.

PMID- 21730413
TI  - Low-plasma and high-temperature PECVD grown silicon-rich SiO(x) film with
      enhanced carrier tunneling and light emission.
AB  - Low-plasma and high-temperature chemical vapor deposition of Si-rich SiO(x) for
      concurrently enhancing the carrier tunneling and light emission efficiency is
      investigated. The O/Si composition ratio of the SiO(x) film significantly
      decreases from 2 to 1.2 as the substrate temperature increases from 200 to 400 
      degrees C, corresponding to the enhanced precipitation of Si nanocrystals in the
      Si-rich SiO(x). In comparison with stoichiometric SiO(2), the Si-L(2,3)
      transition induced kinetic energy loss of the primary electron transmitted
      through the Si-rich SiO(x) sample grown at 400  degrees C is red-shifted by 5 eV.
      The strongest Si nanocrystal related photoluminescence (PL) can be obtained from
      the Si-rich SiO(x) film prepared at a threshold plasma power of 30 W and
      substrate temperature of 400  degrees C. In low-plasma and high-temperature
      deposited samples, the threshold Fowler-Nordheim (F-N) tunneling field and the
      indium tin oxide (ITO)-SiO(x) junction potential barrier height of ITO/SiO(x) /p
      Si/Al metal-oxide-semiconductor light emitting diodes (MOSLEDs) are concurrently
      reduced due to the increasing density of Si nanocrystals precipitated within the
      SiO(x) matrix. A thermal activation energy of 0.8 eV was observed for initiating
      the F-N tunneling process in the MOSLEDs. The electroluminescence (EL) intensity
      and efficiency of the MOSLEDs are improved by at least 10 dB due to the oxygen
      deficient plasma enhanced chemical vapor deposition (PECVD) of Si-rich SiO(x) at
      low plasma power and high temperatures.

PMID- 21730414
TI  - Optimal design of integrally gated CNT field-emission devices using a genetic
      algorithm.
AB  - A method to optimize the focusing quality of integrally gated CNT field-emission
      (FE) devices by combining field-emission modeling and a computational
      intelligence technique, genetic algorithm (GA), is proposed and demonstrated. In
      this work, the e-beam shape, as a characteristic parameter of electron-optical
      properties, is calculated by field-emission simulation modeling. Using a design
      tool that combines GA and physical modeling, a set of structural and electrical
      parameters for four FE device groups, including double-gate, triple-gate,
      quadruple-gate and quintuple-gate type, were optimized. The resultant FE devices
      exhibit satisfactory e-beam focusabilities and the extracted parameters with the
      best performance for each type of FE device were represented to be fabricated by
      a VLSI technique. The GA-based automatic design parameter extraction will
      significantly benefit the design of integrated electron-optical systems for
      versatile vacuum micro- and nano-electronic applications.

PMID- 21730415
TI  - Three-dimensional assembly of single-walled carbon nanotube interconnects using
      dielectrophoresis.
AB  - We present a hybrid approach that combines top-down fabrication with bottom-up
      directed assembly for making single-walled carbon nanotube (SWNT) based three
      dimensional interconnects. The SWNTs are assembled using dielectrophoresis at
      room temperature on a microfabricated 3D platform. The two-terminal resistance of
      the assembled SWNTs at 10 Vpp assembly voltage is approximately 545 Omega.
      Simulation of the dielectrophoretic assembly is carried out to understand the
      behavior of the SWNTs during assembly. Encapsulation of these devices using a
      conformal pinhole-free parylene layer resulted in a decrease of the total
      resistance.

PMID- 21730416
TI  - Gate voltage dependent characteristics of p-n diodes and bipolar transistors
      based on multiwall CN(x)/carbon nanotube intramolecular junctions.
AB  - The electrical transport characteristics of multiwall CN(x)/carbon nanotube
      intramolecular junctions were studied. The junctions could be used as diodes. We
      found that the rectification resulted from p-n junctions, not from metal
      semiconductor junctions. The gate effect was very weak when the diodes were
      reverse biased. At forward bias, however, some of the p-n diodes could be n-type
      transistors. Experimental results supported the opinion that the gate voltage
      dependent property is derived from the Schottky barrier between the CN(x) part
      and the electrode. Using p-n diodes, a bipolar transistor with nanoscale
      components was built, whose behavior was very similar to that of a conventional
      planar bipolar transistor.

PMID- 21730417
TI  - Molecular sensing with the tunnel junction of an Au nanogap in solution.
AB  - The tunnel junction of a gold nanogap was fabricated electrochemically for a
      molecular sensing device in solution. The tunnel junction was sensitive enough to
      detect the variation of a potential barrier within the nanogap, such as the
      chemical adsorption of molecules. By monitoring the variation of the tunneling
      current, which represents the change of a potential barrier due to molecular
      adsorption, the molecules could be detected.

PMID- 21730418
TI  - Mechanical manifestations of rare atomic jumps in dynamic force microscopy.
AB  - The resonance frequency and the excitation amplitude of a silicon cantilever have
      been measured as a function of distance to a cleaved KBr(001) surface with a low
      temperature scanning force microscope (SFM) in ultrahigh vacuum. We identify two
      regimes of tip-sample distances. Above a site-dependent critical tip-sample
      distance reproducible data with low noise and no interaction-induced energy
      dissipation are measured. In this regime reproducible SFM images can be recorded.
      At closer tip-sample distances, above two distinct atomic sites, the frequency
      values jump between two limiting curves on a timescale of tens of milliseconds.
      Furthermore, additional energy dissipation occurs wherever jumps are observed. We
      attribute both phenomena to rarely occurring changes in the tip apex
      configuration which are affected by short-range interactions with the sample.
      Their respective magnitudes are related to each other. A specific candidate two
      level system is also proposed.

PMID- 21730419
TI  - Nanoscale deformation measurement of microscale interconnection assemblies by a
      digital image correlation technique.
AB  - The continuous miniaturization of microelectronic devices and interconnections
      demand more and more experimental strain/stress analysis of micro- and nanoscale
      components for material characterization and structure reliability analysis. The
      digital image correlation (DIC) technique, with the aid of scanning probe
      microscopes, has become a very promising tool to meet this demand. In this study,
      an atomic force microscope (AFM) was used to scan and digitally image micro
      interconnection assemblies in a micro-thermoelectric cooler. AFM images of the
      scan region of interest were obtained separately when the microelectronic device
      was operated before and after the cooling and heating stages. The AFM images were
      then used to obtain the in-plane deformation fields in the observed region of the
      micro-assembly. AFM image correlation is performed for nanoscale deformation
      analysis using the authors' AFM-DIC program. The results show that the observed
      region was subjected to cyclic strains when the device worked between its cooling
      and heating stages, and cyclic strain in the vertical direction was found to be a
      significant deformation mode. The thermally induced deformation behavior of the
      micro-assembly device was modeled by finite element analysis (FEA). Both thermal
      electric analysis and thermal stress analysis were conducted on a 3D finite
      element model of the device. It is shown that the experimental results were able
      to validate the finite element analysis results.

PMID- 21730420
TI  - Dynamics of probes attached to quartz tuning forks for the detection of surface
      forces.
AB  - The dynamics of force microscopy probes attached to quartz tuning fork
      piezoelectric sensors has been investigated, by simply modeling the tuning
      fork/probe system as two coupled damped harmonic oscillators. Depending on how
      probes are applied to the tuning fork prong, they could show appreciable
      compliance along the direction of approach to the surface. In particular,
      buckling or bending deformation of the probe may account for unexpectedly long
      interaction ranges found in experimental approach curves. Some peculiar curves
      found in the literature in the case of lateral probe oscillation (shear force)
      are well reproduced by the present model. In particular, a 'clamping' effect is
      observed when the probe is substantially more compliant than the tuning fork. By
      calculating the actual probe motion along with the tuning fork response, the
      correct distance control operation regimes are pointed out for the shear-force
      case, even when using compliant probes. The model can be readily extended to the
      case of normal oscillation, at least for small amplitudes. Furthermore, it could
      be applied to a 'mixed' case of shear-force detection performed with very
      compliant probes. The present analysis can help to improve data interpretation
      and operation conditions in dynamic force microscopy and spectroscopy.

PMID- 21730421
TI  - Highly ordered uniform single-crystal Bi nanowires: fabrication and
      characterization.
AB  - A mechanical pressure injection technique has been used to fabricate uniform
      bismuth (Bi) nanowires in the pores of an anodic aluminum oxide (AAO) template.
      The AAO template was prepared from general purity aluminum by a two-step
      anodization followed by heat treatment to achieve highly ordered nanochannels.
      The nanowires were then fabricated by an injection technique whereby the molten
      Bi was injected into the AAO template using a hydraulic pressure method. The Bi
      nanowires prepared by this method were found to be dense and continuous with
      uniform diameter throughout the length. Electron diffraction experiments using
      the transmission electron microscope on cross-sectional and free-standing
      longitudinal Bi nanowires showed that the majority of the individual nanowires
      were single crystalline, with preferred orientation of growth along the [011]
      zone axis of the pseudo-cubic structure. The work presented here provides an
      inexpensive and effective way of fabricating highly ordered single-crystalline Bi
      nanowires, with uniform size distributions.

PMID- 21730422
TI  - Water-repellent coating: formation of polymeric self-assembled monolayers on
      nanostructured surfaces.
AB  - In this paper, we suggest a facile and effective method for water-repellent
      coating of oxide surfaces. As a coating material, we synthesized a new random
      copolymer, referred to as poly(TMSMA-r-fluoroMA), by the radical polymerization
      of 3-(trimethoxysilyl)propyl methacrylate (TMSMA) and a fluoromonomer((r))
      bearing methacrylate moiety (fluoroMA). The random copolymer was designed to
      consist of a 'surface-reactive part' (trimethoxysilyl group) for anchoring onto
      oxide-based surfaces and a 'functional part' (perfluoro group) for water
      repellency. The polymeric self-assembled monolayers (pSAMs) of poly(TMSMA-r
      fluoroMA) were constructed on three different aluminum oxide substrates, such as
      flat, concave-textured, and nanoporous plates, and the static water contact angle
      of each surface before and after the formation of pSAMs was measured. The
      formation of pSAMs resulted in significantly enhanced hydrophobicity compared
      with the corresponding bare surfaces. In particular, among three poly(TMSMA-r
      fluoroMA)-coated surfaces, the nanoporous plate showed the highest water
      repellent property, with a static contact angle of ~163 degrees , which is
      indicative of superhydrophobic surfaces.

PMID- 21730423
TI  - Synthesis and characterization of gold nanodogbones by the seeded mediated growth
      method.
AB  - Novel gold nanodogbones (GDBs) are successfully fabricated using a simple seeded
      mediated growth (SMG) method. The shapes of GDBs depend on the amount of added
      vitamin C solvent. The amount of vitamin C solvent was varied from 10 to 40 ul to
      investigate the influence of vitamin C solvent on the GDBs. It is found that the
      aspect ratios (R) of GDBs were in the range from 2.34 to 1.46, and the UV-vis
      absorption measurement revealed a pronounced blueshift on the longitudinal
      surface plasmon resonance (SPR) band from 713 to 676 nm. The GDBs were determined
      by x-ray diffraction (XRD) to be single-crystalline with a face-centered cubic
      (fcc) structure. The lattice constant calculated from this selected-area electron
      diffraction (SAED) pattern is 4.068 A.

PMID- 21730424
TI  - Growth and characterization of stoichiometric tungsten oxide nanorods by thermal
      evaporation and subsequent annealing.
AB  - Stoichiometric tungsten oxide (WO(3)) nanorods are synthesized on tungsten (W)
      substrates by a high-temperature, catalyst-free, physical deposition process and
      by subsequent annealing in oxygen atmosphere. Tungsten oxide nanorods are grown
      by thermal evaporation of WO(3) powder at elevated temperature in a tube furnace.
      XRD, TEM and XPS analysis shows that the as-grown nanorods are single crystalline
      and non-stoichiometric (WO(x)). Annealing of WO(x) nanorods at 700  degrees C
      under oxygen atmosphere has led to the formation of stoichiometric WO(3) as
      evidenced by XRD, XPS and Raman analysis.

PMID- 21730425
TI  - Epitaxial growth of ZnO layers using nanorods with high crystalline quality.
AB  - Epitaxial ZnO films were grown on c-plane sapphire substrates by metal-organic
      chemical vapor deposition using a ZnO multi-dimensional structure having the
      sequence of ZnO film/ZnO nanorods/sapphire. The vertically well-aligned one
      dimensional ZnO nanorods were grown epitaxially on the sapphire substrate with in
      plane alignment under suitable growth conditions and then used as seeds for the
      subsequent epitaxial ZnO layer. For the transition of the ZnO structures from the
      nanorods to the film, the growth temperature and working pressure were
      controlled, while keeping the other conditions fixed. The growth of the ZnO films
      on the well-aligned ZnO nanorods results in homoepitaxial growth with the
      identical orientation relationship along the in-plane direction as well as the
      same c-axis orientation. The microstructural analysis of the multi-dimensional
      structure and analysis of the microstructural evolution from the one-dimensional
      nanorods to the two-dimensional film were conducted using transmission electron
      microscopy.

PMID- 21730426
TI  - Preparation of an ultra fast binding cement from calcium silicate-based mixed
      oxide nanoparticles.
AB  - Building construction takes time, in part because the binding process of cement
      is based on the slow re-crystallization and precipitation of calcium silicate
      species. Since the material's reactivity is surface area limited, a reduction in
      particle size of Portland cements has been used to prepare faster binding
      formulations. The present work investigates a new and direct, one-step
      preparation of calcium silicate-based nanoparticles of a typical Portland cement
      composition by flame spray synthesis. Isothermal calorimetry revealed that the
      hardening of this new nano-cement corroborated a more than tenfold increase of
      initial reactivity with different reaction kinetics if compared to conventionally
      prepared cements. At present, the unfavourably high porosity of nano-cements,
      however, underlines the need for additional improvements of chemical composition
      and formulation to make these highly reactive materials applicable to modern
      construction work, where load-bearing strength is of importance.

PMID- 21730427
TI  - Improved field emission properties of thiolated multi-wall carbon nanotubes on a
      flexible carbon cloth substrate.
AB  - In this paper we report the observation of enhanced field emission properties
      from thiolated multi-wall carbon nanotubes (MWCNTs) produced by a simple and
      effective two-step chemical surface modification technique. This technique
      implements carboxylation and thiolation on the MWCNTs synthesized by microwave
      plasma chemical vapor deposition (MPCVD) on the flexible carbon cloth substrate.
      The resulting thiolated MWCNTs were found to have a very low threshold field
      value of 1.25 V um(-1) and a rather high field enhancement factor of 1.93 *
      10(4), which are crucial for applications in versatile vacuum microelectronics.

PMID- 21730428
TI  - Collapse and stability of single- and multi-wall carbon nanotubes.
AB  - The collapse and stability of carbon nanotubes (CNTs) have important implications
      for their synthesis and applications. While nanotube collapse has been observed
      experimentally, the conditions for the collapse, especially its dependence on
      tube structures, are not clear. We have studied the energetics of the collapse of
      single- and multi-wall CNTs via atomistic simulations. The collapse is governed
      by the number of walls and the radius of the inner-most wall. The collapsed
      structure is energetically favored about a certain diameter, which is 4.12, 4.96
      and 5.76 nm for single-, double- and triple-wall CNTs, respectively. The CNT
      chirality also has a strong influence on the collapsed structure, leading to
      flat, warped and twisted CNTs, depending on the chiral angle.

PMID- 21730429
TI  - Effect of microwave annealing temperatures on lead zirconate titanate thin films.
AB  - Lead zirconate titanate (Pb(1.1)(Zr(0.52)Ti(0.48))O(3)) thin films of thickness
      260 nm on Pt/Ti/SiO(2)/Si substrates were densified by 2.45 GHz microwave
      annealing. The PZT thin films were annealed at various annealing temperatures
      from 400 to 700  degrees C for 30 min. X-ray diffraction showed that the
      pyrochlore phase was transformed to the perovskite phase at 450  degrees C and
      the film was fully crystallized. The secondary (again pyrochlore) phase was
      observed in the PZT thin films, which were annealed above 550  degrees C. The
      surface morphologies were changed above 550  degrees C of the PZT thin films due
      to the secondary phase. Higher dielectric constant (epsilon(r)) and lower
      dielectric loss coercive field (E(c)) were achieved for the 450  degrees C film
      than for the other annealed films.

PMID- 21730430
TI  - Analogous mechanical behaviors in [Formula: see text] and [Formula: see text]
      directions of Cu nanowires under tension and compression at a high strain rate.
AB  - This study analyzes the plastic deformation on the atomic scale of Cu nanowires
      (NWs) with [Formula: see text] and [Formula: see text] orientations during
      uniaxial tension and compression, using a molecular dynamic simulation. The
      maximum local stress (MLS) method is employed to evaluate mechanical behavior
      during deformation. Following yielding, the flow stress strongly depends on the
      variation in the degree of orientation caused by twinning. Both the tension of
      the [Formula: see text] NW and the compression of the [Formula: see text] NW
      cause twin deformation and consequent geometrical softening. In contrast, the
      compression of the [Formula: see text] NW and the tension of the [Formula: see
      text] NW form twin bands and cause geometrical hardening. These behaviors result
      in the stress-strain curves that reveal the pseudo-skew-symmetry characteristic.
      With respect to the difference between the critical resolved shear stress
      (tau(c)) associated with the distinct orientations, tau(c) depends strongly on
      the surface critical resolved stress (tau(sc)). Under tension, tau(sc) depends on
      the degree of lattice distortion. A larger lattice distortion (pre-tensile
      stress) corresponds to higher tau(sc). However, under compression, a geometrical
      factor can be used to describe the difference in tau(sc) between the different
      orientations. A larger geometrical factor corresponds to a larger tau(sc).

PMID- 21730431
TI  - Non-Gaussian fluctuation in the charge transport of Si nanochains.
AB  - The stability of the tunneling charge transport of a tangle of Si nanochains is
      investigated at high bias voltages using a micromanipulator in a scanning
      electron microscope. We confirm that the influence of electron injection due to
      the electron beam of a scanning electron microscope on the charge transport
      properties of nanochains is negligible when the electrode gap is small and the
      bias voltage is large. Under such conditions, current-time curves show large
      fluctuations. We find that the fluctuation is not a simple Brownian motion, but
      its distribution function can be fitted well by a Levy distribution. Its origin
      is discussed in terms of percolation theory.

PMID- 21730432
TI  - Dual surface plasmon resonances in Zn nanoparticles in SiO(2): an experimental
      study based on optical absorption and thermal stability.
AB  - Metallic zinc nanoparticles (NPs) of 5-15 nm in diameter, formed in silica glass
      (SiO(2)) by Zn ion implantation of 60 keV, showed a strong ultraviolet absorption
      peak at around 4.8 eV, which has been assigned as the surface plasmon resonance
      (SPR) of Zn NPs, and another small peak at 1.2 eV, which has never been reported
      before. To identify the origin of the 1.2 eV peak, the correlations of thermal
      stability between the two peaks and Zn NPs were evaluated under annealing both in
      a vacuum (pure thermal stability) and in oxygen gas (thermal oxidation
      stability). The well-correlated stability between the 1.2 eV peak, the 4.8 eV
      peak and Zn NPs indicates that the 1.2 eV peak is not ascribed to radiation
      induced defects but to the Zn NPs. The 1.2 eV peak can be ascribed to an SPR of
      Zn NPs in SiO(2), because the peak satisfies the criterion of the SPR of metallic
      NPs. Since the 4.8 eV peak is also expected to satisfy the criterion, Zn NPs in
      SiO(2) have two SPRs at 1.2 and 4.8 eV.

PMID- 21730433
TI  - Design and function of molecular and bioelectronics devices.
AB  - Further rapid progress of electronics, in particular the increase of computer
      power and breakthroughs in sensor technology for industrial, medical diagnostics
      and environmental applications, strongly depends on the scaling of electronic
      devices, ultimately to the size of molecules. Design of controllable molecular
      scale devices may resolve the problem of energy dissipation at the nanoscale and
      take advantage of molecular self-assembly in the so-called bottom-up approach.
      This special issue of Nanotechnology is devoted to a better understanding of the
      function and design of molecular-scale devices that are relevant to future
      electronics and sensor technology. Papers contained in this special issue are
      selected from the symposium Nano and Giga Challenges in Electronics and
      Photonics: From Atoms to Materials to Devices to System Architecture (12-16
      March, 2007, Phoenix, Arizona, USA), as well as from original and novel
      scientific contributions of invited world-renown researchers. It addresses both
      theoretical and experimental achievements in the fields of molecular and
      bioelectronics, chemical and biosensors at the molecular level, including carbon
      nanotubes, novel nanostructures, as well as related research areas and industrial
      applications. The conference series Nano and Giga Challenges in Electronics and
      Photonics was launched as a truly interdisciplinary forum to bridge scientists
      and engineers to work across boundaries in the design of future information
      technologies, from atoms to materials to devices to system architecture.
      Following the first two successful meetings in Moscow, Russia (NGCM2002) and
      Krakow, Poland (NGCM2004), the third Nano and Giga Forum (NGC2007) was held in
      2007 hosted by Arizona State University. Besides this special issue of
      Nanotechnology, two other collections (in the journal Solid State Electronics and
      the tutorial book in the series Nanostructure Science and Technology Springer)
      have published additional selected and invited papers from NGC2007. The NGC2007
      meeting, which included two days of tutorials (Spring School) and a three day
      symposium, attracted approximately 400 participants from academic, industrial and
      governmental research institutions from 41 countries, and covered recent
      developments in the fabrication and functionality of nano-scale materials,
      devices and system architecture from advanced CMOS to molecular electronics,
      photonics, optoelectronics and magnetic materials and devices. The success of the
      conference would not have been possible without generous support from many
      sponsors and research institutions, especially from Arizona State University
      (conference host and co-organizer), International Science and Technology Center
      (ISTC), National Science Foundation (NSFT), Defense Advanced Research Agency
      (DARPA), Office of Naval Research, Army Research Office, Computational Chemistry
      List (CCL), Springer Publisher, City of Tempe, STMicroelectronics, Quarles &
      Brady LLP, Oak Ridge National Laboratory, Canadian Consulate in Phoenix, Salt
      River Project (SRP) and many other local, national and international and
      individual supporters. We would like to acknowledge the shared responsibility for
      this special issue of Nanotechnology on molecular and bioelectronics, and the
      highly professional support from Dr Nina Couzin, Dr Alex Wotherspoon and the
      Nanotechnology team from the IOP Publishing. We also acknowledge the exception
      made in allowing the publication of some material that is outside the normal
      scope of Nanotechnology.

PMID- 21730434
TI  - Real-time conductivity analysis through single-molecule electrical junctions.
AB  - Conductance through single-molecule junctions, consisting of
      nanoparticle/molecule/nanoparticle units between nanoscale planar electrodes, was
      monitored in real time during several process sequences, including
      dielectrophoretic directed self-assembly and post-assembly modification. Assembly
      faults are directly detected in real time when non-ideal assembly conditions
      result in molecular junction failure and nanoparticle fusion in the junction. The
      real-time conductivity measured through the junction was sensitive to ambient
      conditions, and changes persisted over several days of exposure. Atomic layer
      deposition of Al(2)O(3) was used to encapsulate and isolate the molecular
      junctions, and the effect of the deposition process sequence on current through
      the junction was evaluated in real time. Results indicate that the current
      measured during atomic layer deposition is sensitive to the chemical oxidation
      and reduction reactions proceeding in the 1-2 nm confined region between
      assembled nanoparticles.

PMID- 21730435
TI  - Breakdown of a gold nanowire between electrodes.
AB  - Deformation behavior of an atomic Au wire placed between Au electrodes was
      investigated by using a generalization of the method of linear muffin-tin
      orbitals (LMTO) within the local-density approximation (LDA). We studied the
      dynamical motion of the atoms in the wire. Soft phonon modes were studied. It has
      been found that collective motions are dominated by motions perpendicular to the
      wire axis. Large displacements which resulted in wire breakage were also studied.
      The energy barrier associated with this process has been calculated.

PMID- 21730436
TI  - Carbonyl mediated conductance through metal bound peptides: a computational
      study.
AB  - Large increases in the conductance of peptides upon binding to metal ions have
      recently been reported experimentally. The mechanism of the conductance switching
      is examined computationally. It is suggested that oxidation of the metal ion
      occurs after binding to the peptide. This is caused by the bias potential placed
      across the metal-peptide complex. A combination of configurational changes, metal
      ion involvement and interactions between carbonyl group oxygen atoms and the gold
      leads are all shown to be necessary for the large improvement in the conductance
      seen experimentally. Differences in the molecular orbitals of the nickel and
      copper complexes are noted and serve to explain the variation of the improvement
      in conductance upon binding to either a nickel or copper ion.

PMID- 21730437
TI  - Current measurements in a wide dynamic range-applications in electrochemical
      nanotechnology.
AB  - Current measurements in a wide dynamic range from low picoamperes up to a few
      milliamperes are usually carried by implementing logarithmic current-to-voltage
      converter circuits. Conductance studies in nanoscale metal | molecule | metal
      junctions require measurements with a high dynamic range, good accuracy and
      reasonable speed simultaneously. In this work we propose two novel circuit
      solutions which comply with these conditions: one is based on a high-accuracy,
      fine-tunable logarithmic current-to-voltage converter. Another circuit implements
      a double-output (or multiple-output) linear current-to-voltage converter, for
      which the problem of range-switching has been circumvented. Both circuits were
      applied in constructing a low-current bipotentiostat dedicated to the
      electrochemical formation of molecular-scale gaps, and a novel scanning
      tunnelling microscope preamplifier stage for current-distance spectroscopy
      studies.

PMID- 21730438
TI  - Accurate determination of multiple sets of single molecular conductance of Au/1,6
      hexanedithiol/Au break junctions by ultra-high vacuum-scanning tunneling
      microscope and analyses of individual current-separation curves.
AB  - The effect of the binding sites of the terminal groups -S on gold on currents
      through a single molecular junction (MJ) of Au/1,6-hexanedithiol/Au was studied
      by measuring current-separation (i-s) curves during repeated formation of a break
      junction in UHV-STM. Three different single molecular conductance (SMC) values
      (i.e. G(m)(HC), G(m)(MC) and G(m)(LC)) were found by a careful analysis of
      corrected current histograms for background tunneling currents using a previously
      developed robust statistical analysis. Here, HC, MC and LC represent a single MJ
      with high, medium and low conductance, respectively. These three SMC values are
      attributed to three different contact modes (i.e. strong-strong, strong-weak (or
      weak-strong) and weak-weak bindings at the two ends). In addition to these three
      SMC values due to the different contacts, another lower SMC value was newly
      observed in the corrected histogram. The presence of the fourth SMC is specific
      to MJs of alkanedithiols and is attributable to LC of a single alkylene chain
      with gauche rich conformation, which has a lower SMC value than that of LC with
      all-trans conformation as proposed previously (Fujihira M et al 2006 Phys. Chem.
      Chem. Phys. 8 3876). Due to the effects of the contact and the conformational
      change, it was difficult to determine six different SMC values corresponding to
      two different conformations (i.e. gauche-rich versus all-trans) with three
      different contacts (i.e. HC, MC and LC). In addition to this complexity, the
      current steps corresponding to HC, MC and LC almost always appeared in this order
      in measured i-s curves during separation. The current step observed here could
      not only be a contribution from a single molecule, but also contributions from a
      few groups of molecules that happen to link gold atoms of the substrate with
      those of the tip apex. Therefore, the SMC value for HC obtained as a peak or a
      set of peaks in the current histogram could be based upon the sum of the current
      of HC and those of MCs and LCs coexisting in parallel, unless every MJ would
      change successively from HC to MC and MC to LC. Namely, the currents through
      coexisting MCs and LCs would raise the intrinsic current observed for HC itself,
      while those through coexisting LCs would raise the intrinsic current for MC. To
      avoid such errors in determining the true SMC, we demonstrate here a new method
      based upon analyses of individual i-s curves referred to as jump height analyses
      of individual i-s curves. By this method, the true SMC of LC(all-trans) was
      determined to be 1.6 nS (i.e. G(m) (LC, all-trans) of 2.1 * 10(-5)G(o)) without
      ambiguity in spite of the possible presence of LCs(gauche rich) in parallel.

PMID- 21730439
TI  - Negative differential resistance at sequential single-electron tunnelling through
      atoms and molecules.
AB  - We have carried out calculations of electron transport in single-electron
      transistors using single atoms or small molecules as single-electron islands. The
      theory is based on a combination of (i) the general theory of the sequential
      single-electron transport through objects with a quantized energy spectrum,
      developed by Averin and Korotkov, (ii) the ab initio calculation of molecular
      orbitals and energy spectra within the density functional theory framework (using
      the NRLMOL software package), and (iii) Bardeen's approximation for the rate of
      tunnelling due to wavefunction overlap. The results show, in particular, that dc
      I-V curves of molecular-scale single-electron transistors typically have extended
      branches with negative differential resistance. This effect is due to the
      enhancement of one of the two tunnelling barriers of the transistor by the source
      drain electric field, and apparently has already been observed experimentally by
      at least two groups. In conclusion, the possibility of using this effect for
      increasing the density and performance of hybrid semiconductor/nanodevice
      integrated circuits is discussed in brief.

PMID- 21730440
TI  - Molecular simulations of stretching gold nanowires in solvents.
AB  - The effect of solvent on the elongation of gold nanowires has been further
      studied through molecular simulations. For a simple Lennard-Jones solvent
      (propane), which is a non-bonded solvent, extensive molecular dynamics (MD) runs
      demonstrated that below the melting point of gold nanowires, the solvent effect
      on the elongation properties of Au nanowires is minimal. In thiol organic liquid,
      such as in benzenedithiol (BDT), the situation is much more complicated due to
      the Au-BDT chemical bonding. Here, we present the initial adsorption structure of
      BDT on a stretched gold nanowire through grand canonical Monte Carlo (GCMC)
      simulations. A recently developed force field for the BDT-Au chemical bonding was
      implemented in the simulations. We found that the packing density of the bonded
      BDT on the surface of Au nanowire is larger than that on an extended Au(111)
      surface. The results from this work are helpful in understanding the underlying
      mechanism of the formation of Au-BDT-Au junctions implemented in molecular
      conductance measurements.

PMID- 21730441
TI  - Mechanism of spatially resolved photochemical control of the resistivity of a
      molecular crystalline solid.
AB  - By maintaining alpha-Ag(DM)(2) (DM = C(10)H(8)N(4)) around room temperature (RT)
      ([Formula: see text]) during ultraviolet-visible (UV-vis) irradiation, a series
      of photochemical products named beta was obtained. The solid beta was comprised
      of structurally different compounds. All of the solid beta phases share the
      original chemical formula of Ag(DM)(2) and exhibit semiconducting behaviour, yet
      they differ from each other in their XRD patterns. They are divided into two
      phases: beta1 and beta2. Compared with the XRD pattern of the alpha phase, the
      beta1 phase exhibited XRD peaks at the same 2theta-angles but with different
      relative intensities, while the beta2 phase exhibited totally different XRD
      patterns from those of the alpha or beta1 phases. The actual composition of a
      particular solid of 'beta' phase is dependent upon irradiation time, and can be
      controlled continuously. Around RT, the alpha phase exhibits metallic
      conductivity, while the beta1 and beta2 phases are suggested to be
      semiconductors. As a result, one can continuously and finely control the
      electrical resistivity of Ag(DM)(2) by UV irradiation to modify it into a mixture
      of alpha, beta1 and/or beta2 phases.

PMID- 21730442
TI  - Crystal structures and transistor properties of phenyl-substituted
      tetrathiafulvalene derivatives.
AB  - The crystal structures, thin-film properties, and field-effect transistor (FET)
      characteristics of tetrathiafulvalene (TTF) derivatives with two phenyl groups
      are systematically investigated. The highest mobility, 0.11 cm(2) V(-1) s(-1), is
      observed in biphenyl-substituted TTF (1). The correlation between the crystal
      structures and the FET properties demonstrates that good transistor properties
      are associated with two-dimensional intermolecular interaction, which is achieved
      when the molecules are standing nearly perpendicular to the substrate. Since
      these TTF derivatives are strong electron donors, the use of a metallic charge
      transfer salt (TTF)(TCNQ) as the source and drain electrodes has resulted in a
      considerable reduction of the off current (TCNQ: tetracyanoquinodimethane).

PMID- 21730443
TI  - Tunnelling in alkanes anchored to gold electrodes via amine end groups.
AB  - For investigation of electron transport on the nanoscale, a system possessing a
      simple-to-interpret electronic structure is composed of alkane chains bridging
      two electrodes via end groups; to date, the majority of experiments and
      theoretical investigations on such structures have considered thiols bonding to
      gold electrodes. Recently experiments show that well-defined molecular
      conductances may be resolved if the thiol end groups are replaced by amines. In
      this theoretical study, we investigate the bonding of amine groups to gold
      clusters and calculate electron transport across the resulting tunnel junctions.
      We find very good agreement with recent experiments for alkane diamines and
      discuss differences with respect to the alkane dithiol system.

PMID- 21730444
TI  - The effect of hydrogen evolution reaction on conductance quantization of Au, Ag,
      Cu nanocontacts.
AB  - We have mechanically fabricated Au, Ag, and Cu nanocontacts in solution under
      electrochemical potential control. At the hydrogen evolution potential,
      fractional conductance peaks appeared near 0.5 G(0) (G(0) = 2e(2)/h) in the
      conductance histogram of Au and Cu. This fractional conductance peak was not
      observed in the conductance histogram of Ag. In the case of Au nanocontacts in 50
      mM H(2)SO(4) solution, a 0.1 G(0) peak appeared in the conductance histogram, as
      well as the 0.5 G(0) peak. The origin of the fractional conductance peak and its
      metal dependence are discussed based on previously reported values of metal
      hydrogen binding energy, which was estimated by the exchange current density for
      the hydrogen evolution reaction.

PMID- 21730445
TI  - A theoretical study of molecular conduction: IV. A three-terminal molecular
      device.
AB  - We discuss the features of a three-terminal molecular device and the control of
      electric current using a gate terminal. We introduce a capacitance model to
      investigate the effect of the gate terminal that could reduce to a two-terminal
      molecule for a very small gate capacitance. Therefore, this capacitance model can
      be used in the framework of ordinary ab initio quantum chemical methods. We show
      the effect of the gate terminal analytically using a simple Huckel method.
      Moreover, we used our capacitance model with a nonequilibrium Green's function
      (NEGF)-based Hartree-Fock (HF) approach to study the gate control features of the
      benzenedithiolate molecule, and we show that the current through the molecule can
      be modulated by the gate voltage in the case of a high gate control parameter. We
      also discuss the molecule's response to the applied bias voltage. It is found
      that the molecular charging effect has a strong influence on the behavior of
      molecular-based electronic devices.

PMID- 21730446
TI  - Ab initio correlation effects on the electronic and transport properties of
      metal(II)-phthalocyanine-based devices.
AB  - Using first-principles calculations in the framework of density functional
      theory, we investigated the electronic and transport properties of metal(II)
      phthalocyanine (M(II)Pc) systems, both in a single-molecule configuration and in
      a model device geometry. In particular, using copper(II)-Pc and manganese(II)-Pc
      as prototypical examples, we studied how electronic correlations on the central
      metal ion influence the analysis of the electronic structure of the system and we
      demonstrated that the choice of the exchange-correlation functional, also beyond
      the standard local or gradient corrected level, is of crucial importance for a
      correct interpretation of the data. Finally, our electronic transport simulations
      have shown that M(II)Pc-based devices can act selectively as molecular
      conductors, as in the case of copper, or as spin valves, as in the case of
      manganese, demonstrating once more the great potential of these systems for
      molecular nanoelectronics applications.

PMID- 21730447
TI  - The quantum interference effect transistor.
AB  - We give a detailed discussion of the quantum interference effect transistor
      (QuIET), a proposed device which exploits the interference between electron paths
      through aromatic molecules to modulate the current flow. In the off state,
      perfect destructive interference stemming from the molecular symmetry blocks the
      current, while in the on state, the current is allowed to flow by locally
      introducing either decoherence or elastic scattering. Details of a model
      calculation demonstrating the efficacy of the QuIET are presented, and various
      fabrication scenarios are proposed, including the possibility of using conducting
      polymers to connect the QuIET with multiple leads.

PMID- 21730448
TI  - The effect of the number of parallel DNA molecules on electric charge transport
      through 'standing DNA'.
AB  - We present morphological and electrical characterization of double-stranded DNA
      (dsDNA) molecules covalently bound to two metal electrodes: an underlying gold
      surface and a gold nanoparticle (GNP). Conductive atomic force microscope (cAFM)
      with a metallized tip is used to perform current-voltage (I-V) measurements
      through dsDNA molecules, connected to GNPs of different diameters 5, 10 and 20
      nm. The number of DNA molecules coating the GNP is expected to vary with the
      surface area of the GNP. This number and the portion of the GNP surface area
      enabling hybridization of the DNA determine the number of DNA molecules
      connecting the GNP to the gold surface. The larger the diameter of the GNP the
      higher the expected number of dsDNA molecules connecting it to the gold surface
      and thus the expected current. Our results show similar currents for all three
      GNP sizes, indicating that current flows through the same number of molecules
      regardless of the diameter of the measured GNP. The measured currents, 220 nA at
      2 V, are in accordance with our previous reports (Cohen et al 2005 Proc. Natl
      Acad. Sci. USA 102 11589-93; Cohen et al 2006 Faraday Discuss. 131 367-76) in
      which we demonstrated the validity of the experimental system. In particular, for
      the 5 nm GNP, we conclude that the current possibly flows through two to three
      molecules, likely only one, and that a single short dsDNA molecule can support at
      least ~70 nA, and probably 220 nA.

PMID- 21730449
TI  - Water vapor detection with individual tin oxide nanowires.
AB  - Individual tin oxide nanowires (NWs), contacted to platinum electrodes using
      focused ion beam assisted nanolithography, were used for detecting water vapor
      (1500-32 000 ppm) in different gaseous environments. Responses obtained in
      synthetic air (SA) and nitrogen atmospheres suggested differences in the sensing
      mechanism, which were related to changes in surface density of the adsorbed
      oxygen species in the two cases. A model describing the different behaviors has
      been proposed together with comparative evaluation of NW responses against
      sensors based on bulk tin oxide. The results obtained on ten individual devices
      (tested >6 times) revealed the interfering effect of water in the detection of
      carbon monoxide and illustrated the intrinsic potential of nanowire-based devices
      as humidity sensors. Investigations were made on sensitivity, recovery time and
      device stability as well as surface-humidity interactions. This is the first step
      towards fundamental understanding of single-crystalline one-dimensional (1D) tin
      oxide nanostructures for sensor applications, which could lead to integration in
      real devices.

PMID- 21730450
TI  - Fundamental building blocks for molecular biowire based forward error-correcting
      biosensors.
AB  - This paper describes the fabrication, characterization and modeling of
      fundamental logic gates that can be used for designing biosensors with embedded
      forward error-correction (FEC). The proposed logic gates (AND and OR) are
      constructed by patterning antibodies at different spatial locations along the
      substrate of a lateral flow immunosensor assay. The logic gates operate by
      converting binding events between an antigen and an antibody into a measurable
      electrical signal using polyaniline nanowires as the transducer. In this study,
      B. cereus and E. coli have been chosen as model pathogens. The functionality of
      the AND and OR logic gates has been validated using conductance measurements with
      different pathogen concentrations. Experimental results show that the change in
      conductance across the gates can be modeled as a log-linear response with respect
      to varying pathogen concentration. Equivalent circuits models for AND and OR
      logic gates have been derived based on measured results.

PMID- 21730451
TI  - Single-strand DNA molecule translocation through nanoelectrode gaps.
AB  - Molecular dynamics simulations were performed to investigate the translocation of
      single-strand DNA through nanoscale electrode gaps under the action of a constant
      driving force. The application behind this theoretical study is a proposal to use
      nanoelectrodes as a screening gap as part of a rapid genomic sequencing device.
      Preliminary results from a series of simulations using various gap widths and
      driving forces suggest that the narrowest electrode gap that a single-strand DNA
      can pass is ~1.5 nm. The minimum force required to initiate the translocation
      within nanoseconds is ~0.3 nN. Simulations using DNA segments of various lengths
      indicate that the minimum initiation force is insensitive to the length of DNA.
      However, the average threading velocity of DNA varies appreciably from short to
      long DNA segments. We attribute such variation to the different nature of drag
      force experienced by the short and long DNA segments in the environment. It is
      found that DNA molecules deform significantly to fit in the shape of the nanogap
      during the translocation.

PMID- 21730452
TI  - Benzo-homologated nucleobases in a nanotube-electrode set-up for DNA sequencing.
AB  - Motivated by the possibility that the conductivity signatures of benzo
      homologated DNA bases could be used to sequence DNA, we have investigated the
      conductivity properties of these bases when they are non-covalently sandwiched
      between two (5,5) nanotube electrodes. It is found that these bases conduct
      poorly, making it very difficult to distinguish them. An analysis of the changes
      in the conductivity of benzo-adenine as a function of the distance between the
      tips of the nanotubes revealed that, even though the conductance increases by
      four orders of magnitude when the electrodes are brought closer together, the net
      conductance remains rather small. These results suggest that benzo-homologated
      bases, despite having smaller HOMO-LUMO gaps than their natural counterparts,
      when non-covalently bound to the electrodes cannot be used to sequence DNA by
      means of conductivity measurements.

PMID- 21730453
TI  - Towards local electromechanical probing of cellular and biomolecular systems in a
      liquid environment.
AB  - Electromechanical coupling is ubiquitous in biological systems, with examples
      ranging from simple piezoelectricity in calcified and connective tissues to
      voltage-gated ion channels, energy storage in mitochondria, and electromechanical
      activity in cardiac myocytes and outer hair cell stereocilia. Piezoresponse force
      microscopy (PFM) originally emerged as a technique to study electromechanical
      phenomena in ferroelectric materials, and in recent years has been employed to
      study a broad range of non-ferroelectric polar materials, including piezoelectric
      biomaterials. At the same time, the technique has been extended from ambient to
      liquid imaging on model ferroelectric systems. Here, we present results on local
      electromechanical probing of several model cellular and biomolecular systems,
      including insulin and lysozyme amyloid fibrils, breast adenocarcinoma cells, and
      bacteriorhodopsin in a liquid environment. The specific features of PFM operation
      in liquid are delineated and bottlenecks on the route towards nanometre
      resolution electromechanical imaging of biological systems are identified.

PMID- 21730454
TI  - Individually addressable crystalline conducting polymer nanowires in a
      microelectrode sensor array.
AB  - An efficient, site-specific and scalable approach has been developed to produce
      high-quality and individually addressable conducting polymer nanowire electrode
      junctions (CPNEJs) in a parallel-oriented array. Polypyrrole and PEDOT conducting
      polymer nanowires (CPNWs) with uniform diameters (ca. 60-150 nm) were introduced
      into the desired electrode junctions in a precise manner by performing a three
      step constant-current electrochemical process at a low current density and a low
      concentration of monomers. A low scan rate, cyclic voltammetric method was also
      employed and gave similar results. These CPNEJ arrays function as a miniaturized
      sensor for the parallel and real-time detection of gas and organic vapour. The
      electrochemical approaches utilized allow the conducting polymer chains to self
      organize in the CPNWs to form novel polycrystalline structures, observed by high
      resolution TEM. The weak diffraction rings at 4.88 A and 4.60 A were observed for
      PEDOT and polypyrrole CPNWs, respectively.

PMID- 21730455
TI  - Temporal and steric analysis of ionic permeation and binding in SERCA via
      molecular dynamic simulations.
AB  - The availability of the crystal structure of the sarco(endo)plasmic reticulum
      calcium ATPase (SERCA) has allowed atomic-level molecular dynamic (MD)
      simulations of this membrane transport protein to be done. The biomedical and
      nanotechnological implications of this work are discussed as well as the methods
      of performing the simulations and analysis. We have performed nanosecond
      timescale simulations of SERCA for several of its known conformations in a
      lipid/water environment. One simulation contained Ca(2+) ions, while others
      without ions were analyzed by techniques such as steric pathway determination. We
      discuss details of the resulting putative cytoplasmic and lumenal pathways, along
      with experimental evidence from the literature to support our conclusions.
      Finally, we give a brief overview of future research directions, as they pertain
      to MD simulations and their analysis. The methodology used in this work shows
      that significant insight into the structure-function relationship of ion-motive
      transmembrane pumps can be derived by a combination of simulation tools and
      analysis techniques including MD trajectories, steric analysis and electrostatic
      potentials.

PMID- 21730456
TI  - Energetics and electronic structures of AlN nanotubes/wires and their potential
      application as ammonia sensors.
AB  - Aluminium nitride (AlN) one-dimensional (1D) nanostructures, including
      crystalline nanowires, faceted nanotubes and conventional single-walled
      nanotubes, were investigated by means of density functional theory (DFT) using
      the generalized gradient approximation (GGA). While the larger diameter
      crystalline nanowires are the most favoured energetically of all these 1D
      nanostructures, the thick faceted nanotubes have comparable binding energies and
      can be obtained experimentally. The single-walled nanotubes have the lowest
      binding energies, and are less feasible experimentally. Due to the surface states
      at the band edges, the band gaps of all the AlN 1D nanostructures are much
      smaller than that of bulk AlN. The band structures of AlN nanowires can be
      modified by NH(3) adsorption. Consequently AlN nanowires have potential
      applications as gas sensors, since their electronic structures are very sensitive
      to NH(3) adsorption.

PMID- 21730457
TI  - Anisotropy of the thermoelectric power in superlattices.
AB  - Anisotropy of the thermoelectric power in superlattices on the scattering of
      charge carriers by impurity ions is studied. The thermopower anisotropy is found
      to be significant at the small degree of band filling. It has been shown that the
      concentration dependence of the transverse component of the thermopower is
      nonmonotonic.

PMID- 21730458
TI  - Wiring efficiency of a metallizable DNA linker for site-addressable
      nanobioelectronic assembly.
AB  - We report the first demonstration of DNA oligonucleotide tags used to address the
      site-specific assembly of multiple redox enzymes onto spatially distinct regions
      of a nanoelectronic platform, establishing a direct electrical contact. The
      resulting system constitutes a multiplexed carbon nanotube-redox protein
      biosensor capable of detecting varying concentrations of several different
      substances in real time. The efficiency and robustness of the enzyme linking
      scheme is explored in detail, showing a high degree of preservation of enzymatic
      activity and an efficient electrical contact at the enzyme-nanoelectrode
      interface. While five proteins have been used as a demonstration in this study,
      there is virtually no limit to the number of enzymes that could be bound in
      parallel using this linking strategy, which is universally applicable to all
      proteins due to the simple conjugation chemistry involved. We further demonstrate
      metallization of the linker in the presence of a divalent metal cation, inducing
      elevated electron transfer efficiency relative to the native DNA link.

PMID- 21730459
TI  - Ab initio simulation of magnetic tunnel junctions.
AB  - In this paper, we present the mathematical and implementation details of an ab
      initio method for calculating spin-polarized quantum transport properties of
      atomic scale spintronic devices under external bias potential. The method is
      based on carrying out density functional theory (DFT) within the Keldysh non
      equilibrium Green's function (NEGF) formalism to calculate the self-consistent
      spin densities. We apply this method to investigate nonlinear and non-equilibrium
      spin-polarized transport in a Fe/MgO/Fe trilayer structure as a function of
      external bias voltage.

PMID- 21730460
TI  - Blinking suppression and intensity recurrences in single CdSe-oligo(phenylene
      vinylene) nanostructures: experiment and kinetic model.
AB  - We report time-resolved single molecule fluorescence imaging of individual CdSe
      quantum dots that are functionalized with oligomeric conjugated organic ligands.
      The fluorescence intensity trajectories from these composite nanostructures
      display both a strong degree of blinking suppression and intensity fluctuations
      with characteristic recurrence times on the order of 10-60 s. In addition,
      fluorescence decay rate measurements of individual hybrid nanostructures indicate
      significantly modified non-radiative quantum dot decay rates relative to
      conventional ZnS-capped CdSe quantum dots. We show that a modified diffusive
      reaction coordinate model with slow fluctuations in quantum dot electron energies
      (1S(e), 1P(e)) can reproduce the experimentally observed behaviour.

PMID- 21730461
TI  - Theoretical modelling of carrier transports in molecular semiconductors:
      molecular design of triphenylamine dimer systems.
AB  - Charge transport in molecular systems and biosystems can be different from that
      in inorganic, rigid semiconductors. The electron-nuclear motion couplings play an
      important role in the former case. We have developed a theoretical scheme to
      employ the Marcus electron transfer theory coupled with a direct diabatic dimer
      model and the Brownian diffusion assumption to predict the carrier mobility for
      molecular materials. For triphenylamine, a typical molecular transport material,
      the design strategies regarding the formation a cyclic or a linear dimer are
      evaluated from theoretical calculations for the carrier mobility. We made a
      comparison between the mobility and the electrical polarizability. It is found
      that in the case of triphenylamine dimer, these two quantities have different
      trends. The fact that the macrocycle possesses higher mobility but lower
      polarizability than the linear chain is due to the difference in the
      reorganization energy. The theoretical predicted temperature dependences are
      analysed within the hopping mechanism. The calculated room-temperature mobilities
      are in reasonable agreement with experimental values.

PMID- 21730462
TI  - Steric effects and chirality in the adsorption of glycine and phenylglycine on
      Cu(110).
AB  - Glycine adsorbed on Cu(110) forms (marginally) heterochiral (3 * 2) reconstructed
      overlayers, in contrast to phenylglycine preferring homochiral adsorption.
      Density-functional theory within generalized gradient approximation is used to
      identify the origin of this difference. We find the restriction of the molecular
      relaxation imposed by the phenyl group in conjunction with intermolecular
      hydrogen bonds to be responsible.

PMID- 21730463
TI  - Stabilization of exotic minority phases in a multicomponent self-assembled
      molecular network.
AB  - Trimesic acid (TMA) and alcohols were recently shown to self-assemble into a
      stable, two-component linear pattern at the solution/highly oriented pyrolytic
      graphite (HOPG) interface. Away from equilibrium, the TMA/alcohol self-assembled
      molecular network (SAMN) can coexist with pure-TMA networks. Here, we report on
      some novel characteristics of these non-equilibrium TMA structures, investigated
      by scanning tunneling microscopy (STM). We observe that both the chicken-wire and
      flower-structure TMA phases can host 'guest' C(60) molecules within their pores,
      whereas the TMA/alcohol SAMN does not offer any stable adsorption sites for the
      C(60) molecules. The presence of the C(60) molecules at the solution/solid
      interface was found to improve the STM image quality. We have taken advantage of
      the high-quality imaging conditions to observe unusual TMA bonding geometries at
      domain boundaries in the TMA/alcohol SAMN. Boundaries between aligned TMA/alcohol
      domains can give rise to doubled TMA dimer rows in two different configurations,
      as well as a tripled-TMA row. The boundaries created between non-aligned domains
      can create geometries that stabilize TMA bonding configurations not observed on
      surfaces without TMA/alcohol SAMNs, including small regions of the previously
      predicted 'super flower' TMA bonding geometry and a tertiary structure related to
      the known TMA phases. These structures are identified as part of a homologic
      class of TMA bonding motifs, and we explore some of the reasons for the
      stabilization of these phases in our multicomponent system.

PMID- 21730464
TI  - Tuning the conductance of carbon nanotubes with encapsulated molecules.
AB  - It was recently shown that a molecule encapsulated inside a carbon nanotube can
      be used to devise a novel type of non-volatile memory element. At the heart of
      the mechanism for storing and reading information is the new concept of a
      molecular gate where the molecule acts as a passive gate that hinders the flow of
      electrons for a given position relative to the nanotube host. By systematically
      exploring the effects of encapsulation of an acceptor molecule in a series of
      carbon nanotubes, we show that the reliability of the memory mechanism is very
      sensitive to the interaction between the nanotube host and the molecule guest.

PMID- 21730465
TI  - Transport in multiterminal graphene nanodevices.
AB  - We study the transport properties of multiterminal graphene nanodevices using the
      Landauer-Buttiker approach and the tight binding model. We consider a four
      terminal device made at the crossing of a zigzag and armchair nanoribbons and two
      types of T-junction devices. The transport properties of graphene multiterminal
      devices are highly sensitive to the details of the junction region. Thus the
      properties are drastically different from those on the armchair and zigzag
      counterparts. In the cross-junction device, we see a conductance dip in the
      armchair lead associated with a conductance peak in the zigzag lead. We find that
      this effect is enhanced in a T-junction device with one armchair sidearm.

PMID- 21730466
TI  - Channelling of dipolar molecules through carbon nanotubes.
AB  - We study the dynamic polarization of carbon nanotubes caused by the propagation
      of fast electric dipoles under channelling conditions. We specifically analyse
      the position and orientation dependences of the dipole self-energy, stopping
      force, and the torque about the dipole centre. It is found that a dipole is
      strongly attracted to the nanotube wall and shows a tendency to orient itself
      perpendicular to the direction of motion. The stopping force shows more complex
      behaviour, but is generally found to be larger close to the nanotube wall and
      when oriented in the perpendicular direction at higher speeds.

PMID- 21730467
TI  - Current instability of carbon nanotube field effect transistors.
AB  - The current instability of carbon nanotube field effect transistors (CNTFETs) is
      systematically studied under the influence of applied voltages, surfactants and
      temperatures. The devices were fabricated from carbon nanotubes and sodium
      dodecyl benzene sulfonate (SDBS) suspension using an ac dielectrophoresis (DEP)
      technique. The source and drain current for as-prepared p-type CNTFETs show an
      increase with time for the on-state, but a decrease for the off-state.
      Comparisons between constant and intermittent biasing conditions reveal that
      mobile ions could be the origin of the current instability. After removal of
      adsorbed SDBS, opposite transient behaviors of the current were observed, which
      can be attributed to the charge trapping induced screening effect.

PMID- 21730468
TI  - The effect of phonon scattering on the switching response of carbon nanotube
      field-effect transistors.
AB  - The performance of carbon nanotube field-effect transistors is analyzed
      numerically, using the non-equilibrium Green's function formalism. The effect of
      electron-phonon scattering on both the DC and switching response of these devices
      is studied. For the calculation of the switching response, the quasi-static
      approximation is assumed. The role of the electron-phonon coupling strength and
      phonon energy are investigated. Our results indicate that scattering with high
      energy phonons reduces the on-current only weakly, but can increase the switching
      time considerably due to charge pile-up in the channel. Conversely, scattering
      with low-energy phonons reduces the on-current more effectively, but has a weaker
      effect on the switching time.

PMID- 21730469
TI  - Protective effect of maghemite nanoparticles on ultraviolet-induced photo-damage
      in human skin fibroblasts.
AB  - This study examined the optical properties of an oxidized form of maghemite
      (gamma-Fe(2)O(3)) nanoparticles and their protective effects against the
      photoaging of human skin fibroblasts irradiated with ultraviolet (UV) light.
      Nanoparticles with diameters ranging from 8.7 to 12 nm were prepared using a
      chemical co-precipitation method. The nanoparticles were coated with two
      surfactants to obtain a water-based product. The onset of the absorption of the
      gamma-Fe(2)O(3) nanoparticles in the UV-visible absorption spectra increased with
      increasing particle size. The gamma-Fe(2)O(3) nanoparticles significantly
      inhibited the production of matrix metalloproteinase-1 in human skin fibroblast
      HS 68 cells by 60% compared with the UV-irradiated control. These results suggest
      that gamma-Fe(2)O(3) nanoparticles have photoprotective properties, and have
      potential use as an agent against photoaging.

PMID- 21730470
TI  - Feasibility study of logic circuits with a spin wave bus.
AB  - We present a feasibility study of logic circuits utilizing spin waves for
      information transmission and processing. As an alternative approach to the
      transistor-based architecture, logic circuits with a spin wave bus do not use
      charge as an information carrier. In this work we describe the general concept of
      logic circuits with a spin wave bus and illustrate its performance by numerical
      simulations based on available experimental data. Theoretical estimates and
      results of numerical simulations on signal attenuation, signal phase velocity,
      and the minimum spin wave energy required per bit in the spin bus are obtained.
      The transport parameters are compared with ones for conventional electronic
      transmission lines. The spin wave bus is not intended to substitute traditional
      metal interconnects since it has higher signal attenuation and lower signal
      propagation speed. The potential value of a spin wave bus is, however, an
      interface between electronic circuits and integrated spintronics circuits. The
      logic circuits with a spin wave bus allow us to provide wireless read-in and read
      out.

PMID- 21730471
TI  - Room-temperature single-electron transistors using alkanedithiols.
AB  - We have fabricated single-electron transistors by alkanedithiol molecular self
      assembly. The devices consist of spontaneously formed ultrasmall Au nanoparticles
      linked by alkanedithiols to nanometer-spaced Au electrodes created by
      electromigration. The devices reproducibly exhibit addition energies of a few
      hundred meV, which enables the observation of single-electron tunneling at room
      temperature. At low temperatures, tunneling through discrete energy levels in the
      Au nanoparticles is observed, which is accompanied by the excitations of
      molecular vibrations at large bias voltage.

PMID- 21730472
TI  - Preparation and electrical properties of electrospun tin-doped indium oxide
      nanowires.
AB  - Well-aligned tin-doped indium (ITO) nanowires have been prepared using the
      electrospinning process. The Sn doping mechanism and microstructure have been
      characterized by x-ray diffraction (XRD) and x-ray photoelectron spectroscopy
      (XPS). Devices for I-V measurement and field-effect transistors (FETs) were
      assembled using ITO nanowires with top contact configurations. The effect of Sn
      doping on the electrical conductivity was significant in that it enhanced the
      conductance by over 10(7) times, up to ~1 S cm(-1) for ITO nanowires with an Sn
      content of 17.5 at.%. The nanowire FETs were operated in the depletion mode with
      an electron mobility of up to 0.45 cm(2) V(-1) s(-1) and an on/off ratio of
      10(3).

PMID- 21730473
TI  - Boron nitride stamp for ultra-violet nanoimprinting lithography fabricated by
      focused ion beam lithography.
AB  - Cubic boron nitride (c-BN) is one of the hardest known materials (second after
      diamond). It has a high level of chemical resistance and high UV transmittance.
      In this study, a stamp for ultra-violet nanoimprint lithography (UV-NIL) was
      fabricated using a bi-layered BN film deposited on a quartz substrate. Deposition
      of the BN was done using RF magnetron sputtering. A hexagonal boron nitride (h
      BN) layer was deposited for 30 min before c-BN was deposited for 30 min. The
      thickness of the film was measured as 160 nm. The phase of the c-BN layer was
      investigated using Fourier transform infrared (FTIR) spectrometry, and it was
      found that the c-BN layer has a 40% cubic phase. The deposited film was patterned
      using focused ion beam (FIB) lithography for use as a UV-NIL stamp. Line patterns
      were fabricated with the line width and line distance set at 150 and 150 nm,
      respectively. The patterning process was performed by applying different currents
      to observe the effect of the current value on the pattern profile. The fabricated
      patterns were investigated using AFM, and it was found that the pattern
      fabricated by applying a current value of 50 picoamperes (pA) has a better
      profile with a 65 nm line depth. The UV transmittance of the 160 nm thick film
      was measured to be 70-86%. The hardness and modulus of the BN was measured to be
      12 and 150 GPa, respectively. The water contact angle of the stamp surface was
      measured at 75 degrees . The stamp was applied to UV-NIL without coating with an
      anti-adhesion layer. Successful imprinting was proved via scanning electron
      microscope (SEM) images of the imprinted resin.

PMID- 21730474
TI  - Fabrication of silicon dioxide submicron channels without nanolithography for
      single biomolecule detection.
AB  - We successfully fabricated nanochannel arrays with silicon dioxide (SiO(2))
      surfaces for single biomolecule detection. The SiO(2) nanochannel fabrication is
      based on the combination of anisotropic etching by potassium hydroxide (KOH)
      solution, local oxidation of silicon (LOCOS) and plasma etching of silicon. This
      fabrication technique is easily controllable and is a simple and practical
      solution for low-cost and high-throughput fabrication of nanofluidic channels.
      Thus, this technique enables the generation of nanochannels with various
      nanoscale dimensions without using nanolithography.

PMID- 21730475
TI  - Nanoporous polymeric transmission gratings for high-speed humidity sensing.
AB  - Nanoporous polymeric transmission gratings are demonstrated to be an excellent
      platform for high-speed optical humidity sensing. The grating structures were
      fabricated with a modified holographic, polymer-dispersed liquid crystal (H-PDLC)
      system. The sensing mechanism was based on changes in the relative transmission
      associated with the adsorption and desorption of water vapour by nanopores. The
      spectral changes due to varying humidity levels were measured by a spectrometer
      and compared with the calculated results based on the coupled wave theory. When
      the relative humidity (RH) changed from 40% to 95%, the relative transmission at
      475 nm increased from 6.3% to 46.6% and that at 702 nm increased from 4% to 64%;
      these results indicate the sensor's high sensitivity. In addition, the sensor
      demonstrated excellent reversibility and reproducibility over a large RH range
      (from 20% to 100% RH). Moreover, the response time of the sensor was measured to
      be less than 350 ms, making it suitable for many high-speed humidity-sensing
      applications.

PMID- 21730476
TI  - Nanoscale domain switching behaviour in polycrystalline ferroelectric thin films.
AB  - We report on the nanoscale domain switching behaviour in polycrystalline
      tetragonal perovskite lead zirconate titanate (PZT) ferroelectric thin films
      investigated via piezoresponse force microscopy (PFM). Local domain structures
      were imaged as a function of varying biasing conditions and spatial location of
      the tip within 50-100 nm sized grains. Nanoscale piezoresponse images provided
      direct visual evidence of the complex interplay between electrical and mechanical
      fields in a polycrystalline system, which causes effects such as correlated
      switching between the grain of interest and neighbouring grains, ferroelastic
      domain switching, inhomogeneous piezostrain profiles and domain pinning on very
      minute length scales. Detailed investigations on mechanisms which induce such
      domain behaviour are presented.

PMID- 21730477
TI  - Electron transport through supported biomembranes at the nanoscale by conductive
      atomic force microscopy.
AB  - We present a reliable methodology to perform electron transport measurements at
      the nanoscale on supported biomembranes by conductive atomic force microscopy (C
      AFM). It allows measurement of both (a) non-destructive conductive maps and (b)
      force controlled current-voltage characteristics in wide voltage bias range in a
      reproducible way. Tests experiments were performed on purple membrane monolayers,
      a two-dimensional (2D) crystal lattice of the transmembrane protein
      bacteriorhodopsin. Non-destructive conductive images show uniform conductivity of
      the membrane with isolated nanometric conduction defects. Current-voltage
      characteristics under different compression conditions show non-resonant
      tunneling electron transport properties, with two different conduction regimes as
      a function of the applied bias, in excellent agreement with theoretical
      predictions. This methodology opens the possibility for a detailed study of
      electron transport properties of supported biological membranes, and of soft
      materials in general.

PMID- 21730478
TI  - Synthesis of Ba-doped CeO(2) nanowires and their application as humidity sensors.
AB  - Ba-doped CeO(2) nanowires were obtained from CeO(2) particles through a facile
      composite-hydroxide-mediated (CHM) route. The products were characterized by x
      ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM),
      transmission electron microscopy (TEM) and high-resolution transmission electron
      microscope (HRTEM). The formation process of the product was discussed. Humidity
      sensors based on the source material CeO(2) particles, Ba-doped CeO(2) nanowires
      grown for 12 and 72 h, were fabricated. The responses to humidity for static and
      dynamic testing proved that both doping Ba into CeO(2) and converting morphology
      into a nanowire can improve the humidity sensitivity. The resistance changes from
      465 to 3.9 MOmega as the relative humidity (RH) increases from 25% to 88%,
      indicating promising applications of Ba-doped CeO(2) nanowires in environmental
      monitoring.

PMID- 21730479
TI  - Electrochemical impedance measurement of prostate cancer cells using carbon
      nanotube array electrodes in a microfluidic channel.
AB  - Highly aligned multi-wall carbon nanotubes were synthesized in the shape of
      towers and embedded into fluidic channels as electrodes for impedance measurement
      of LNCaP human prostate cancer cells. Tower electrodes up to 8 mm high were grown
      and easily peeled off a silicon substrate. The nanotube electrodes were then
      successfully soldered onto patterned printed circuit boards and cast into epoxy
      under pressure. After polishing the top of the tower electrodes, RF plasma was
      used to enhance the electrocatalytic effect by removing excess epoxy and
      activating the open end of the nanotubes. Electrodeposition of Au particles on
      the plasma-treated tower electrodes was done at a controlled density. Finally,
      the nanotube electrodes were embedded into a polydimethylsiloxane (PDMS) channel
      and electrochemical impedance spectroscopy was carried out with different
      conditions. Preliminary electrochemical impedance spectroscopy results using
      deionized water, buffer solution, and LNCaP prostate cancer cells showed that
      nanotube electrodes can distinguish the different solutions and could be used in
      future cell-based biosensor development.

PMID- 21730480
TI  - Moment switching in nanotube magnetic force probes.
AB  - Magnetic images of high density vertically recorded media using metal-coated
      carbon nanotube tips exhibit a doubling of the spatial frequency under some
      conditions (Deng et al 2004 Appl. Phys. Lett. 85 6263). Here we demonstrate that
      this spatial frequency doubling is due to the switching of the moment direction
      of the nanotube tip. This results in a signal which is proportional to the
      absolute value of the signal normally observed in MFM. Our modeling indicates
      that a significant fraction of the tip volume is involved in the observed
      switching, and that it should be possible to image high bit densities with
      nanotube magnetic force sensors.

PMID- 21730481
TI  - Homogeneous nanocrystalline cubic silicon carbide films prepared by inductively
      coupled plasma chemical vapor deposition.
AB  - Silicon carbide films with different carbon concentrations x(C) have been
      synthesized by inductively coupled plasma chemical vapor deposition from a
      SiH(4)/CH(4)/H(2) gas mixture at a low substrate temperature of 500  degrees C.
      The characteristics of the films were studied by x-ray photoelectron
      spectroscopy, x-ray diffraction, scanning electron microscopy, high-resolution
      transmission electron microscopy, Fourier transform infrared absorption
      spectroscopy, and Raman spectroscopy. Our experimental results show that, at x(C)
      = 49 at.%, the film is made up of homogeneous nanocrystalline cubic silicon
      carbide without any phase of silicon, graphite, or diamond crystallites/clusters.
      The average size of SiC crystallites is approximately 6 nm. At a lower value of
      x(C), polycrystalline silicon and amorphous silicon carbide coexist in the films.
      At a higher value of x(C), amorphous carbon and silicon carbide coexist in the
      films.

PMID- 21730482
TI  - In situ probing of the growth and morphology in electron-beam-induced deposited
      nanostructures.
AB  - Three series of nanofiber structures were grown via electron-beam-induced
      deposition as a function of beam energy (1, 5 and 20 keV) using a W(CO)(6)
      precursor. At each beam energy a time series ranging from 0.5 to 128 s was
      performed and the sample current during each growth was monitored versus growth
      time. The subsequent current traces have been correlated to the nanostructure
      morphology. For the 1 and 5 keV beam energy, two distinct lateral growth regimes
      were observed. Initially there is a rapid base broadening consistent with the
      electron beam interaction region. Secondly, a lateral 'platelet' type growth was
      observed. At 20 keV beam energy, there is an initial rapid broadening: however,
      no 'platelet' growth is observed. For each beam energy, the measured current
      trace is correlated to the observed growth regimes.

PMID- 21730483
TI  - Surface charge driven size evolution during the formation of self-assembled
      nanostructures from discrete hydrophilic silver nanoparticles.
AB  - We investigate the spontaneous evolution of mercaptosuccinic acid-capped silver
      nanoparticles (MSA-Ag) of size 2.5 +/- 1.0 nm during the formation of assembled
      nanostructures at the air/water interface. In the phase transfer approach induced
      by the cationic surfactant cetyltrimethylammonium bromide (CTAB), the fusion
      among MSA-Ag nanoparticles is notably accelerated owing to the formation of a CTA
      MSA bilayer on the particle surface. Provided that the size-selective separation
      is carried out in advance for these polydisperse MSA-Ag nanoparticles, either a
      unitary or a binary orderly superlattice composed of evolved nanoparticles is
      obtained at the air/water interface. For self-corrective equilibrium growth by
      adjusting the pH value of the bulk solution through the diffusion of HCl vapor, a
      competition is found between the superlattice formation and the size growth. The
      possible size evolution mechanism of each method is proposed. This work also
      shows that controllable evolution is a useful approach to prepare nanostructures
      with structural diversity.

PMID- 21730484
TI  - Hierarchically structured superhydrophobic coatings fabricated by successive
      Langmuir-Blodgett deposition of micro-/nano-sized particles and surface
      silanization.
AB  - The present study demonstrates the creation of a stable, superhydrophobic surface
      by coupling of successive Langmuir-Blodgett (LB) depositions of micro- and nano
      sized (1.5 um/50 nm, 1.0 um/50 nm, and 0.5 um/50 nm) silica particles on a glass
      substrate with the formation of a self-assembled monolayer of
      dodecyltrichlorosilane on the surface of the particulate film. Particulate films,
      in which one layer of 50 nm particles was deposited over one to five sublayers of
      larger micro-sized particles, with hierarchical surface roughness and
      superhydrophobicity, were successfully fabricated. Furthermore, the present 'two
      scale' (micro- and nano-sized particles) approach is superior to the previous
      'one-scale' (micro-sized particles) approach in that both higher advancing
      contact angle and lower contact angle hysteresis can be realized. Experimental
      results revealed that the superhydrophobicity exhibited by as-fabricated
      particulate films with different sublayer particle diameters increases in the
      order of 0.5 um>1.0 um>1.5 um. However, no clear trend between sublayer number
      and surface superhydrophobicity could be discerned. An explanation of
      superhydrophobicity based on the surface roughness introduced by two-scale
      particles is also proposed.

PMID- 21730485
TI  - Self-assembly of versatile tubular-like In(2)O(3) nanostructures.
AB  - Versatile indium oxide tubular nanostructures (well-aligned nanotube arrays,
      flower-like tubular structures, and square nanotubes) were fabricated by a facile
      and reliable chemical vapor deposition (CVD) technique, taking advantage of the
      self-assembly property and substrate-induced epitaxial growth mechanism. The
      technique has a few advantages, such as low growth temperature, nonexistence of
      catalyst, template-free synthesis, direct bonding to the semiconductor
      substrates, etc. This strategy might extend the approach of synthesizing
      desirable nanostructures of other important low-melting metal oxides for
      potential applications.

PMID- 21730486
TI  - One-step synthesis of highly water-soluble LaF(3):Ln(3+) nanocrystals in methanol
      without using any ligands.
AB  - Water-soluble infrared-to-visible fluorescent LaF(3) nanocrystals doped with
      different lanthanide ions (Er(3+)/Yb(3+), Eu(3+), Nd(3+), Tb(3+)) have been
      synthesized in methanol without using any ligands. These nanocrystals are easily
      dispersed in water, producing a transparent colloidal solution. The colloids of
      the Er(3+)/Yb(3+), Eu(3+), Nd(3+), Tb(3+) doped nanocrystals exhibit strong
      luminescence in the visible and near-infrared spectral regions.

PMID- 21730487
TI  - Synthesis of a CNT-grafted TiO(2) nanocatalyst and its activity triggered by a DC
      voltage.
AB  - Carbon nanotube (CNT)-grafted TiO(2) (CNT/TiO(2)) was synthesized as an
      electrically conductive catalyst that exhibits redox ability under electrical
      excitation besides ultraviolet (UV) irradiation. The CNT/TiO(2) material was
      synthesized by a two-step process. Ni nanoparticles were photodeposited onto
      TiO(2) first. The Ni nanoparticles then served as seeds for the growth of CNTs
      using the chemical vapor deposition (CVD) of C(2)H(2). The CNT/TiO(2)
      nanocomposite exhibits strong oxidation activity toward NO gas molecules via both
      photocatalysis under UV irradiation and electrocatalysis under a DC voltage of
      500 V in dark conditions.

PMID- 21730488
TI  - Sm-Co hard magnetic nanoparticles prepared by surfactant-assisted ball milling.
AB  - Hard magnetic nanoparticles based on the Sm(2)Co(17) and SmCo(5) systems have
      been successfully produced using a surfactant-assisted ball milling technique. A
      size-selection process has been developed to obtain nanoparticles of different
      sizes with narrow size distribution. Significant room-temperature coercivity up
      to 3.1 kOe has been achieved with the Sm(2)Co(17)-based nanoparticles of an
      average size of 23 nm. It has been found that surfactants play multifold roles in
      the processing.

PMID- 21730489
TI  - Controlling surface reactions of CdS nanocrystals: photoluminescence activation,
      photoetching and photostability under light irradiation.
AB  - Photoluminescence enhancement, photoetching and photostability of CdS
      nanocrystals were investigated under light irradiation. Strongly photoluminescent
      nanocrystals were obtained when the nanocrystal was weakly photoexcited in an
      aqueous solution at pH = 11 in the presence of oxygen. With the support of XPS
      measurements, the following photoactivation mechanism is proposed: Cd(2+) ions
      are released from the CdS surface owing to slow photocorrosion in the presence of
      oxygen, and Cd-OH bond formation occurs on the CdS surface under the alkaline
      conditions, removing the surface trap states. The wavelength of the irradiating
      light and the pH of the solution were determined as key parameters for
      nanocrystal surface modification. For the stability measurements the nanocrystals
      were extracted with an ammonium salt in a non-polar solvent. The
      photoluminescence quantum yield for the nanocrystals in the non-polar phase
      reached approximately 30%. The extracted nanocrystals were remarkably stable even
      under UV light irradiation, and the photoluminescence intensity was maintained
      for several months.

PMID- 21730490
TI  - Photoluminescence decay kinetics of doped ZnS nanophosphors.
AB  - Doped nanophosphor samples of ZnS:Mn, ZnS:Mn, Co and ZnS:Mn, Fe were prepared
      using a chemical precipitation method. Photoluminescence (PL) spectra were
      obtained and lifetime studies of the nanophosphors were carried out at room
      temperature. To the best of our knowledge, there are very few reports on the
      photoluminescence investigations of Co-doped or Fe-doped ZnS:Mn nanoparticles in
      the literature. Furthermore, there is no report on luminescence lifetime
      shortening of ZnS:Mn nanoparticles doped with Co or Fe impurity. Experimental
      results showed that there is considerable change in the photoluminescence spectra
      of ZnS:Mn nanoparticles doped with X (X = Co, Fe). The PL spectra of the ZnS:Mn,
      Co nanoparticle sample show three peaks at 410, 432 and 594 nm, while in the case
      of the ZnS:Mn, Fe nanoparticle sample the peaks are considerably different. The
      lifetimes are found to be in microsecond time domain for 594 nm emission, while
      nanosecond order lifetimes are obtained for 432 and 411 nm emission in ZnS:Mn, X
      nanophosphor samples. These lifetimes suggest a new additional decay channel of
      the carrier in the host material.

PMID- 21730491
TI  - Meniscus and viscous forces during normal separation of liquid-mediated contacts.
AB  - Menisci form between two solid surfaces with the presence of an ultra-thin liquid
      film. Meniscus and viscous forces contribute to an adhesive force when two
      surfaces are separated. The adhesive force can be very large and can result in
      high friction, stiction and possibly high wear. The situation may become more
      pronounced when the contacting surfaces are ultra-smooth and the normal load is
      small, as is common for micro-/nanodevices. In this study, equations for meniscus
      and viscous forces during separation of two flat surfaces, and a sphere and a
      flat surface, are developed, and the corresponding adhesive forces contributed by
      these two types of forces are examined. The geometric meniscus curvatures and
      break point are theoretically determined, and the role of meniscus and viscous
      forces is evaluated during separation. The influence of separation distance,
      liquid thickness, meniscus area, separation time, liquid properties and contact
      angles are analyzed. Critical meniscus areas at which transition in the dominance
      of meniscus to viscous forces occurs for different given conditions, i.e. various
      initial liquid thicknesses, contact angles and designated separation time, are
      identified. The analysis provides a fundamental understanding of the physics of
      separation process, and insights into the relationships between meniscus and
      viscous forces. It is also valuable for the design of the interface for various
      devices.

PMID- 21730492
TI  - Formation mechanism of nanocrystalline high-pressure phases in silicon during
      nanogrinding.
AB  - The phase transformations of Si under nanogrinding have been studied by
      transmission electron microscopy and Raman spectroscopy. Nanocrystalline high
      pressure phases (Si-III/Si-XII) were found in the amorphous layer of the
      subsurface of heavily ground Si. The sequence of the phase transformation in
      nanogrinding has been found to be different to that in nanoindentation. The
      formation mechanism of the nanocrystalline high-pressure phases in nanogrinding
      is proposed based on experimental results.

PMID- 21730493
TI  - Raman frequency shift in oxygen-functionalized carbon nanotubes.
AB  - Based on density functional theory, the geometrical and electronic structures of
      oxygen-functionalized single-wall carbon nanotubes (O-SWCNs) are obtained, of
      which the vibrational properties are calculated in terms of lattice dynamics
      theory. Both bond expansion and contraction are found to coexist in O-SWCNs. A
      distinct Raman shift is observed in the radial breathing mode (RBM) and the G
      modes, depending not only on the tube diameter and chirality but also on oxygen
      coverage and adsorption configurations. With the oxygen coverage increasing,
      interestingly, a nonmonotonic upshift and downshift is observed in the G modes,
      which is attributed to the competition between the bond expansion and
      contraction. In addition, the resonance Raman effect at different oxygen
      coverage, which may be observable in O-SWCNs, is discussed.

PMID- 21730494
TI  - Homogenous indium distribution in InGaN/GaN laser active structure grown by LP
      MOCVD on bulk GaN crystal revealed by transmission electron microscopy and x-ray
      diffraction.
AB  - We present transmission electron microscopy (TEM) and x-ray quantitative studies
      of the indium distribution in In(x)Ga(1-x)N/GaN multiple quantum wells (MQWs)
      with x = 0.1 and 0.18. The quantum wells were grown by low-pressure metalorganic
      chemical vapour deposition (LP-MOCVD) on a bulk, dislocation-free, mono
      crystalline GaN substrate. By using the quantitative TEM methodology the absolute
      indium concentration was determined from the 0002 lattice fringe images by the
      strain measurement coupled with finite element (FE) simulations of surface
      relaxation of the TEM sample. In the x-ray diffraction (XRD) investigation, a new
      simulation program was applied to monitor the indium content and lateral
      composition gradients. We found a very high quality of the multiple quantum wells
      with lateral indium fluctuations no higher than Deltax(L) = 0.025. The individual
      wells have very similar indium concentration and widths over the whole multiple
      quantum well (MQW) stack. We also show that the formation of 'false clusters' is
      not a limiting factor in indium distribution measurements. We interpreted the
      'false clusters' as small In-rich islands formed on a sample surface during
      electron-beam exposure.

PMID- 21730495
TI  - Controllable phase connectivity and magnetoelectric coupling behavior in
      CoFe(2)O(4)-Pb(Zr,Ti)O(3) nanostructured films.
AB  - Magnetoelectric CoFe(2)O(4)-Pb(Zr,Ti)O(3) nanostructured films with various phase
      connectivity patterns were prepared by a pulsed laser deposition method. It was
      found that the microstructure as well as the phase connectivity pattern of the
      film varied remarkably with the variation of phase content ratio. All composite
      nanofilms exhibit evident ferromagnetic and ferroelectric characteristics, as
      well as distinct magnetoelectric coupling behavior upon increasing the magnetic
      field. The correlation between the phase connectivity pattern and magnetoelectric
      coupling behavior for the composite nanofilm was revealed. This work provides an
      efficient avenue to modulate the magnetoelectric coupling behavior for the
      ferroelectric-ferromagnetic composite nanofilm.

PMID- 21730496
TI  - Controlled surface ordering of endohedral fullerenes with a SrTiO(3) template.
AB  - The ability to select the way in which atoms and molecules self-organize on a
      surface is important for synthesizing nanometre scale devices. Here we show how
      endohedral fullerenes (Er(3)N@C(80)) can be assembled into four distinctive
      arrangements on a strontium titanate surface template. Each template pattern
      correlates to a particular reconstruction on n-doped SrTiO(3)(001), made in whole
      or in part by self-assembled arrays of non-stoichiometric oxide nanostructures.
      Close-packed assemblies of Er(3)N@C(80) molecules are formed, as well as one
      dimensional chains and two-dimensional grids. This method of template-assisted
      molecular ordering provides a new platform for the development of experimental
      schemes of classical and quantum information processing at the molecular level.

PMID- 21730497
TI  - SiGe nanowire growth and characterization.
AB  - Single-crystal SiGe nanowires were synthesized via the vapour-liquid-solid (VLS)
      growth mechanism using disilane and germane as precursor gases. We have
      investigated the effect of temperature, pressure, and the inlet gas ratio on the
      growth and stoichiometry of Si(x)Ge(1-x) nanowires. The nanowires were
      characterized using scanning and transmission electron microscopies and energy
      dispersive x-ray analysis. It was found that nanowires with a Si:Ge ratio of
      about 1 had smooth surfaces, whereas departure from this ratio led to rough
      surfaces. Electrical properties were then investigated by fabricating back-gated
      field effect transistors (using a focused ion beam system) where single SiGe
      nanowires served as the conduction channels. Gated conduction was observed
      although resistance in the undoped devices was high.

PMID- 21730498
TI  - Hierarchical assembly of inorganic nanostructure building blocks to octahedral
      superstructures-a true template-free self-assembly.
AB  - A room temperature, template-free, wet chemical synthesis of ceria nanoparticles
      and their long term ageing characteristics are reported. High resolution
      transmission electron microscopy and UV-visible spectroscopy techniques are used
      to observe the variation in size, structure and oxidation state, respectively as
      a function of time. The morphology variation and the hierarchical assembly
      (octahedral superstructure) of nanostructures are imputed to the inherent
      structural aspects of cerium oxide. It is hypothesized that the 3-5 nm individual
      building blocks will undergo an intra-agglomerate re-orientation to attain the
      low energy configuration. This communication also emphasizes the need for long
      term ageing studies of nanomaterials in various solvents for multiple
      functionalities.

PMID- 21730499
TI  - Nanopattern formation using a chemically modified PS-P4VP diblock copolymer.
AB  - A slight betainization of the amphiphilic block copolymer polystyrene-block
      poly(4-vinylpyridine) (PS-P4VP) was carried out by the introduction of 1,3
      propane sultone into the P4VP block. The micellar film cast from the new
      copolymer solution exhibited hexagonal packing which is similar to the copolymer
      film prior to modification. An interesting core-corona inversion was induced in
      situ with water, a selective solvent for P4VP, due to the increased water
      sensitivity. The effect of annealing on a PS-P4VP-sultone micellar film was
      investigated both with and without solvent environment. The latter gives rise to
      a reduction in the nanodot dimension while the former leads to the formation of a
      nanostrand morphology. This procedure thus adds a simple yet effective tool for
      controlling pattern formation.

PMID- 21730500
TI  - White-light emission from a blend of CdSeS nanocrystals of different Se:S ratio.
AB  - CdSeS nanocrystals with different bandgap energies have been synthesized by the
      colloidal method. The solution blend of blue-, green- and red-emitting CdSeS
      nanocrystals, in appropriate proportions, showed strong white emission of
      different shades on excitation with a UV source. We observed that the CIE
      coordinate of the spectrum of a particular blend is independent of excitation
      wavelength. We also observed that the contribution of self-absorption in energy
      loss in the blend of CdSeS nanocrystals is not very significant. A white-light
      emitting LED has been fabricated by coating a blend mixed with
      polymethylmethacrylate on a commercial UV-LED.

PMID- 21730501
TI  - Conduction intersubband transitions at normal incidence in Si(1-x)Ge(x) quantum
      well devices.
AB  - We show theoretically that it is possible to design SiGe-based quantum well
      structures in which conduction intersubband transitions are induced by normal
      incidence infrared radiation. A sp(3)d(5)s(*) tight binding model has been
      adopted to evaluate the electronic states and optical transitions between lowest
      conduction confined states of a superlattice composed of one pure Ge quantum well
      separated by SiGe alloys, grown along the [001] direction. We find that
      significant optical coupling between confined states in the Ge wells is achieved
      at normal incidence radiation by the off-diagonal elements of the mass tensor.
      The minimum energy Ge conduction valleys are, in fact, tilted with respect to the
      [001] growth axis. For comparison we show that no such coupling can be realized
      for the conduction states confined in a similar structure composed by Si quantum
      wells because the ellipsoids of the lowest conduction valleys are oriented along
      the growth direction.

PMID- 21730502
TI  - Mobility asymmetry in InGaAs/InAlAs heterostructures with InAs quantum wires.
AB  - Strong asymmetry of electron mobility in InGaAs/InAlAs heterostructures (lattice
      matched to InP) with the presence of InAs quantum wires was observed. Self
      assembled InAs quantum wires, embedded in an InGaAs matrix close to the hetero
      interface, has a strong effect in electron conduction in the interface channel.
      The low temperature mobility for electrons moving parallel to the quantum wires
      is much higher than that of electrons moving perpendicular to the wires. The
      asymmetry in mobility is attributed to the difference in scattering cross section
      of the quantum wires in these two directions.

PMID- 21730503
TI  - Biofunctionalization of CeF(3):Tb(3+) nanoparticles.
AB  - CeF(3):Tb(3+) nanoparticles (short pillar-like morphology with an average length
      and width of 11 and 5 nm, respectively) were successfully prepared by a polyol
      process using diethyleneglycol (DEG) as solvent. After being functionalized with
      a SiO(2)-NH(2) layer, these CeF(3):Tb(3+) nanoparticles can be conjugated with
      biotin molecules (activated by thionyl chloride) and further with avidin. The as
      formed CeF(3):Tb(3+) nanoparticles, CeF(3):Tb(3+) nanoparticles functionalized
      with amino groups, biotin conjugated amino-functionalized CeF(3):Tb(3+)
      nanoparticles and biotinylated CeF(3):Tb(3+) nanoparticles bonded with avidin
      were characterized by x-ray diffraction (XRD), transmission electron microscopy
      (TEM), Fourier transform infrared (FT-IR), UV/vis absorption spectra and
      luminescence spectra, respectively. The biofunctionalization of the CeF(3):Tb(3+)
      nanoparticles has less effect on their luminescence properties, i.e. they still
      show strong green emission (from Tb(3+), with (5)D(4)-(7)F(5) at 543 nm as the
      most prominent group), indicative of the great potential for these CeF(3):Tb(3+)
      nanoparticles to be used as biological fluorescence probes.

PMID- 21730504
TI  - Microwave-assisted synthesis of anatase TiO(2) nanorods with mesopores.
AB  - Pure anatase TiO(2) nanorods with mesopores were synthesized by a simple and low
      cost microwave-assisted method when tri-block copolymer was used as a structure
      stabilization agent and TiCl(4) as metal precursor. TEM investigation showed that
      larger nanorods were assembled by pearl-necklace-shaped nanorods following an
      oriented attachment mechanism in a specific direction. A proposed hypothetical
      scheme showed that the formation of lyotropic titania liquid crystal (TLC) serves
      a key role in the stabilization of nanorods, and the mesopores on nanorods are
      derived from the vacancy of inter-particles of nanorods and regions lacking
      inorganic precursors in the TLC structure. Control experiments showed that
      microwave treatment plays a key role in the maintenance of original morphologies
      and mesostructures free from destruction even under high temperature
      calcinations.

PMID- 21730505
TI  - Amorphous carbon contamination monitoring and process optimization for single
      walled carbon nanotube integration.
AB  - We detail the monitoring of amorphous carbon deposition during thermal chemical
      vapour deposition of carbon nanotubes and propose a contamination-less process to
      integrate high-quality single-walled carbon nanotubes into micro
      electromechanical systems. The amorphous content is evaluated by confocal micro
      Raman spectroscopy and by scanning/transmission electron microscopy. We show how
      properly chosen process parameters can lead to successful integration of single
      walled nanotubes, enabling nano-electromechanical system synthesis.

PMID- 21730506
TI  - Synthesis and characterization of europium(III) nanoparticles for time-resolved
      fluoroimmunoassay of prostate-specific antigen.
AB  - Recent advances in the fabrication and bioconjugation of nanometre-sized
      lanthanide(III) chelate particles have led to robust high specific activity
      labels. This paper describes the synthesis and characterization of
      lanthanide(III) nanoparticle labels and the use of a nanoparticle in a
      bioaffinity assay system. Two europium(III) nanoparticles were prepared using an
      extremely simple, inexpensive and fast agglomeration strategy. A silica
      stabilized nanoparticle was synthesized from hydrophobic tris(dibenzoylmethane)
      mono(phenanthroline) and tris(dibenzoylmethane)-mono(5-aminophenanthroline)
      europium(III) chelates in aqueous solution. In addition, a naphthoyl
      trifluoroacetone:tri-n-octylphosphineoxide:sodium dodecyl sulfate europium(III)
      complex was agglomerated in water. The particle sizes ranged from 62 to 140 nm in
      diameter. The silica-stabilized particle was further coated with a monoclonal
      antibody. The analytical performance of the bioconjugated nanoparticle label was
      evaluated in a model sandwich immunoassay of prostate-specific antigen. The
      detection limit of human prostate-specific antigen was 28 ng l(-1), 850 fM, in a
      microtiter plate format using time-resolved fluorometry. The coefficient of
      variation ranged from 1 to 9%. The novel nanoparticle label improves the specific
      activity of existing lanthanide(III) nanoparticle labels and simplifies the
      preparation route. In addition, prepared high-density nanoparticle labels using
      lanthanide(III) chelates or other specific fluorochromes have potential
      applications in a number of other fields.

PMID- 21730507
TI  - Large-scale fabrication of Ag nanoparticles in PVP nanofibres and net-like silver
      nanofibre films by electrospinning.
AB  - Heat treatment of various compositions of AgNO(3)-doped polyvinylpyrrolidone
      (PVP) composite nanofibres fabricated by electrospinning produced two kinds of
      silver species: (i) Ag nanoparticles dispersed in PVP nanofibres, when the
      loading of AgNO(3) was 5 wt%, and (ii) a net-like silver nanofibre film when the
      loading of AgNO(3) was five times greater than that of PVP in the composite
      nanofibres. Scanning electron microscopy (SEM), transmission electron microscopy
      (TEM), UV-visible absorption spectroscopy, FT-IR spectra, powder x-ray
      diffraction (XRD) and x-ray photoelectron spectroscopy (XPS) were used to
      characterize the silver nanoparticles and nanofibres. The formation mechanisms
      are discussed based on the redox reaction between AgNO(3) and PVP during heat
      treatment; essentially, the weight ratios of AgNO(3) to PVP determined the types
      of morphologies, from Ag nanoparticles to silver nanofibre film. The present
      results may find some potential application in the design of new composite
      materials in the dielectric and electronics areas.

PMID- 21730508
TI  - Controllable synthesis of flower- and rod-like ZnO nanostructures by simply
      tuning the ratio of sodium hydroxide to zinc acetate.
AB  - A controlled synthesis of flower- and rod-like ZnO nanostructures in a
      hydrothermal phase has been realized in the absence of an additional template.
      The well-defined morphologies are obtained by simply tuning the ratio of sodium
      hydroxide to zinc acetate in a narrow range. The products are characterized by
      powder x-ray diffraction (XRD), scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). The growth mechanism is suggested to be
      that the supersaturation of the precursor Zn(OH)(4)(2-) results in various
      nucleation habits, which induce the ZnO nanostructures with different
      morphologies.

PMID- 21730509
TI  - Poly(3- hydroxybutyrate)/Bioglass((r)) composite films containing carbon
      nanotubes.
AB  - Poly(3hydroxybutyrate) (P(3HB))/Bioglass((r)) composites incorporating
      multiwalled carbon nanotubes (MWCNTs) have been successfully prepared by the
      solvent casting technique. The microstructure, electrical properties and
      bioactivity of the composites were characterized using scanning electron
      microscopy, x-ray diffraction and current-voltage measurements. Different
      concentrations of MWCNTs were used to determine their effect on the electrical
      properties of the composites. MWCNTs and Bioglass((r)) particles were found to be
      homogeneously dispersed throughout the P(3HB) matrix. The electrical resistance
      of the composite samples decreased on increasing the MWCNT concentration, as
      expected. An in vitro degradation study in simulated body fluid (SBF) was carried
      out on composite samples. The formation of hydroxyapatite on the surfaces of
      P(3HB)/Bioglass((r))/MWCNT composite films was confirmed after two months of
      immersion in SBF. This hydroxyapatite layer was not formed on the neat polymeric
      films and on composites containing MWCNTs only (without Bioglass((r))). It was
      found that the presence of MWCNTs did not hinder the bioactivity of the
      Bioglass((r)) particles, as confirmed by SEM and XRD studies on composite
      samples.

PMID- 21730510
TI  - The constitutive relation and small scale parameter of nonlocal continuum
      mechanics for modelling carbon nanotubes.
AB  - In this paper, the constitutive relations of nonlocal elasticity theory are
      presented for application in the analysis of carbon nanotubes (CNTs) when
      modelled as Euler-Bernoulli beams, Timoshenko beams or as cylindrical shells. In
      particular, the shear stress and strain relation for the nonlocal Timoshenko beam
      theory is discussed in great detail due to a misconception by some researchers
      that the nonlocal effect should appear in this constitutive relation. Different
      theories for proposing the value of the small scale parameter are also introduced
      and a recommendation for the value from the standpoint of wave propagation of
      CNTs is given.

PMID- 21730511
TI  - Batch fabrication of carbon nanotube bearings.
AB  - Relative displacements between the atomically smooth, nested shells in
      multiwalled carbon nanotubes (MWNTs) can be used as a robust nanoscale motion
      enabling mechanism. Here, we report on a novel method suited for structuring
      large arrays of MWNTs into such nanobearings in a parallel fashion. By creating
      MWNT nanostructures with nearly identical electrical circuit resistance and heat
      transport conditions, uniform Joule heating across the array is used to
      simultaneously engineer the shell geometry via electric breakdown. The biasing
      approach used optimizes process metrics such as yield and cycle-time. We also
      present the parallel and piecewise shell engineering at different segments of a
      single nanotube to construct multiple, but independent, high density bearings. We
      anticipate this method for constructing electromechanical building blocks to be a
      fundamental unit process for manufacturing future nanoelectromechanical systems
      (NEMS) with sophisticated architectures and to drive several nanoscale
      transduction applications such as GHz-oscillators, shuttles, memories, syringes
      and actuators.

PMID- 21730512
TI  - Electronic and optical properties of finite carbon nanotubes in an electric
      field.
AB  - The effects, caused by the geometric structure and an electric field (E), on the
      electronic and optical properties of quasi-zero-dimensional finite carbon
      nanotubes are explored by employing the tight-binding model coupled with
      curvature effects. Electronic properties (state energies, symmetry of electronic
      states, energy spacing and state degeneracy) are significantly affected by the
      magnitude and the direction of the electric field and the geometric structure
      (radius, length and chirality). The electric field, by lowering the symmetry of
      finite carbon nanotubes, modifies the electronic properties. Thus, the optical
      excitation spectra, excited by electric polarization parallel to the nanotube
      axis, exhibit rich delta-function-like peaks, which reveal the characteristics of
      the electronic properties. Therefore it follows that geometric structure and E
      influence the low-energy absorption spectra, i.e. the change of frequency of the
      first peak, the alternation of the peak height and the production of the new
      peaks. There are more absorption peaks when E is oriented closer to the cross
      section plane. Moreover, the very complicated optical absorption spectra are
      characteristic for the individual chiral carbon nanotube due to its specific
      geometric structure. Above all, the predicted absorption spectra and the
      associated electronic properties could be verified by optical measurements.

PMID- 21730513
TI  - High spatially resolved morphological, structural and spectroscopical studies on
      copper oxide nanocrystals.
AB  - Copper oxide nanocrystals decorated on multi-wall carbon nanotubes have been
      prepared. Comprehensive morphological, structural and spectroscopical studies
      have been carried out on the nanometre/atomic scale by the combination of high
      resolution transmission electron microscopy and electron energy-loss near-edge
      structure in electron energy-loss spectroscopy, which has a high spatially
      resolved capacity advantage over the normally used analytical techniques such as
      x-ray powder diffraction (XRD) and x-ray photoelectron spectroscopy (XPS). The
      result reveals that highly crystalline cubic Cu(2)O nanocrystals with highly
      uniform dispersion, homogeneous size of about 5.3 nm and nearly spherical
      morphology are synthesized as the predominant phase, while rare individual
      monoclinic CuO nanocrystals with irregular shape are still present as the minor
      phase. The analysis based on the survey result and the structural symmetry
      difference between Cu(2)O and CuO demonstrates that XRD underestimates the
      presence of the CuO phase with much lower structural symmetry while XPS
      overestimates the proportion of CuO phase.

PMID- 21730514
TI  - Characterization of the optical properties of silver nanoparticle films.
AB  - To understand the collective properties of nanoparticles, it is necessary to
      control the particle size, spacing and ordering. Here we describe the chemical
      synthesis of well-controlled silver nanoparticles, the wet coat preparation and
      the optical properties of its film. The light incidence angle and polarization
      dependency of the resonant spectra show distinctive surface plasmon resonance
      extinction peaks for isolated particles and the coupled modes of neighbouring
      particles. Furthermore, we discuss the thermal treatment and dielectric
      surrounding effects on the optical properties of silver nanoparticle film.

PMID- 21730515
TI  - Near-infrared photoluminescence in germanium oxide enclosed germanium nano- and
      micro-crystals.
AB  - We have studied the near-infrared photoluminescence properties of free-standing
      germanium nano-crystals (20 nm on average) and micro-crystals (60 um on average)
      at 80-300 K. Two peaks were observed at ~1.0 and ~1.4 eV from both the nano- and
      micro-crystals. The integrated PL (I(PL)) intensity of the nano-crystals is about
      an order of magnitude stronger than that of the micro-crystals and the I(PL) is
      also enhanced by ageing in air for both crystals. The ~1.0 eV peak position does
      not change with either the crystal size or temperature. We suggest that the deep
      traps located at the interfacial region between the surface GeO(2) layer and the
      bulk crystal Ge is responsible for the near-infrared PL.

PMID- 21730516
TI  - Two-photon-assisted excited state absorption in nanocomposite films of PbS
      stabilized in a synthetic glue matrix.
AB  - Strong nonlinear absorption is observed in nanocomposite films containing PbS
      nanocrystals of mean size of 3.3 nm stabilized in a commercial poly(vinyl
      acetate) glue by a novel and simple chemical route of synthesis. A significant
      blueshift of the optical absorption edge indicates strong quantum confinement.
      The mean nanocrystal size was characterized by x-ray diffraction and transmission
      electron microscopy. The surface structure of nanocrystals is analysed using
      infrared spectroscopy. The excitonic transitions are probed by photoacoustic
      spectroscopy and the results are analysed on the basis of theoretical
      calculations using envelope function formalism. Results of open aperture z-scan
      experiments suggest a model involving saturable absorption followed by two-photon
      absorption at a lower concentration while the data for a higher concentration
      fitted saturable absorption followed by three-photon absorption. Free carrier
      absorption due to two-photon-assisted excited state absorption appears to be the
      predominant mechanism of optical nonlinearity.

PMID- 21730517
TI  - Determination of the natural frequency of a cantilevered ZnO nanowire resonantly
      excited by a sinusoidal electric field.
AB  - The electric-field-induced mechanical resonance of an individual nanotube (NT) or
      nanowire (NW) has been utilized as a versatile technique for in situ measurement
      of the Young's modulus of the NT/NW in electron microscopes. The key step of this
      technique is to determine the fundamental natural frequency of the NT/NW.
      However, the emergence of super- and/or sub-harmonic resonances might make the
      determination uncertain. This paper investigates the resonance behaviour of ZnO
      NWs in a nanotip-nanowire system in order to clarify this obscurity. It is found
      that forced and parametric resonance are two basic modes of the observed multi
      frequency resonances and that each mode exhibits a distinct characteristic. By
      controlling the driving force exerted on the NW to be either lateral or axial,
      the two otherwise entangled modes are clearly separated. Based on this resonance
      mode separation, a criterion for identifying the natural frequency of ZnO NWs is
      proposed.

PMID- 21730518
TI  - Angle-dependent light emission from aligned multiwalled carbon nanotubes under
      CO(2) laser irradiation.
AB  - This paper reports the light emission from aligned multiwalled carbon nanotubes
      (MWNTs) under continuous wave CO(2) laser (lambda = 10.6 um) irradiation. Results
      indicate that the light emission is dependent on the angle theta between the
      laser incident direction and the nanotube axis. The relative intensity of the
      light emission at certain wavelengths shows a Lorentzian feature when theta
      varies from 0 degrees  to 90 degrees . The Lorentzian fitting curve displays a
      distinct tendency between shorter (lambda<600 nm) and longer wavelength
      (lambda>700 nm). A minimum intensity was observed at theta(m) close to 67 degrees
      under shorter wavelength, whereas a maximum intensity was shown at theta(m) of
      about 60 degrees  at longer wavelength. These results show the anisotropic
      property of aligned MWNTs.

PMID- 21730519
TI  - Mechanical properties of super honeycomb structures based on carbon nanotubes.
AB  - As a result of repeating carbon nanotube Y junctions periodically, super
      honeycomb structures have recently been proposed. In this paper, the mechanical
      properties of these structures are investigated by using the shell model of the
      finite element method. The study shows that the super honeycomb structures have
      great flexibility and outstanding capability in force transferring; the network
      configuration increases the ductility of the nanomaterials. Furthermore, it can
      be concluded that the equivalent tensile modulus and Poisson's ratio of super
      structures are dependent on the number of junctions in the width direction.

PMID- 21730520
TI  - Anisotropic growth of gold clusters to gold nanocubes under UV irradiation.
AB  - A chiral reagent, 2-naphthol, has been introduced under alkaline solution as a
      reductant for HAuCl(4) in CTAB micelle to produce exclusively cubic gold
      nanoparticles under UV photoactivation. Prolonged irradiation helped the
      digestion of the primarily evolved spherical particles into smaller gold
      nanocubes, which then act as tiny cubic seeds, leading to the formation of larger
      nanocubes. The smaller cubes take the assistance of CTAB under alkaline condition
      to serve as the seed in directing the transformation of all the spherical
      colloids into cubic shapes under continuous irradiation via Ostwald ripening. The
      shape transformation of the nanoparticles has been monitored by repetitive TEM
      imaging and absorption spectral analysis. The FTIR analysis proves that the gold
      nanocubes are capped by CTAB. The XRD pattern authenticates the formation of the
      fcc gold nanocubes. GCMS studies in turn confirmed the presence of hydroxylation
      of 2-naphthol in the course of the reaction, leaving exclusively cubic gold
      nanoparticles at the final stage of the photoactivation reaction.

PMID- 21730521
TI  - Carbon nanopipettes for cell probes and intracellular injection.
AB  - We developed integrated, carbon-based pipettes with nanoscale dimensions (CNP)
      that can probe cells with minimal intrusion, inject fluids into the cells, and
      concurrently carry out electrical measurements. Our manufacturing technique does
      not require cumbersome nanoassembly and is amenable to mass production. Using
      CNPs, we demonstrate the injection of reagents into cells with minimal intrusion
      and without inhibiting cell growth.

PMID- 21730522
TI  - Electrospun gelatin fiber mats containing a herbal-Centella asiatica-extract and
      release characteristic of asiaticoside.
AB  - Ultra-fine gelatin (type A, porcine skin, ~180 Bloom) fiber mats containing a
      methanolic crude extract of Centella asiatica (L.) Urban, a medicinal plant
      widely known for its traditional medical applications including its wound healing
      ability, were fabricated, for the first time, from the neat gelatin solution (22%
      w/v in 70 vol% acetic acid) containing the crude extract (mCA) in various amounts
      (i.e. 5-30 wt% based on the weight of gelatin powder) by electrospinning.
      Incorporation of mCA in the neat gelatin solution did not affect both the
      morphology and the size of the mCA-loaded gelatin fibers, as both of the neat and
      the mCA-loaded gelatin fibers were smooth and the average diameters of these
      fibers ranged between 226 and 232 nm. The cross-linked mCA-loaded e-spun gelatin
      fiber mat from the neat gelatin solution containing 30 wt% of mCA was further
      investigated for the release characteristic of asiaticoside, identified as the
      most active compound associated with the healing of wounds, in two different
      types of releasing medium, i.e. acetate buffer and the buffer containing 10 vol%
      of methanol, based on the thin-layer chromatography (TLC)-densitometry technique.
      Based on the unit weight of the actual amount of asiaticoside present in the
      specimens, the total amount of asiaticoside released from the fiber mat specimens
      was lower than that from the film counterparts while, based on the unit weight of
      the specimens, an opposite trend was observed.

PMID- 21730523
TI  - Characterization and air pressure sensing of doubly clamped multi-walled carbon
      nanotubes.
AB  - We report the fabrication and characterization of doubly clamped multi-walled
      carbon nanotubes (MWNTs). The devices were assembled by applying an electric
      field while the MWNTs were firmly clamped and suspended at both ends of a thick
      metal trench electrode in solution. The contacts were further processed using a
      focused ion beam. Final dimensions ranged from 100 to 150 nm in diameter and 1.5
      4 um in length. The fabricated devices were characterized by I-V curves,
      impedance measurements, and their mechanical deformation under a high pressure
      airflow. In the latter case, the resistance of a MWNT device varied linearly with
      the magnitude of the air pressure. These characteristics strongly suggest
      potential applications in fields such as nanoelectronics and sensors.

PMID- 21730524
TI  - Functionalization of BN nanotubes with dichlorocarbenes.
AB  - The geometric and electronic structures of dichlorocarbene (CCl(2))
      functionalized BN nanotubes (BNNTs) were studied using density functional theory
      within the generalized gradient approximation. We found that the CCl(2) addition
      favors slanted B-N bonds in zigzag tubes, and the CCl(2)-attached BNNTs prefer
      open rather than closed three-membered-ring (3MR) structures in all the zigzag
      (n,0) BNNTs studied, whereas closed 3MR structure occurs in the CCl(2)-attached
      BN graphene layer. The binding energies decrease with increase of the CCl(2)
      coverage, but the electronic properties of BNNTs do not change significantly,
      irrespective of the CCl(2) coverage.

PMID- 21730525
TI  - GaSb-based lasers with two-dimensional photonic crystal mirrors.
AB  - We present the realization of two-dimensional (2D) photonic crystals (PhCs) on
      the GaSb material system. An electron cyclotron resonance reactive ion etch
      process using Cl(2)/Ar allows the fabrication of PhCs covering air fill factors
      of f = 20%-50%, lattice periods of a = 400-500 nm and aspect ratios of 5:1.
      Quality and reflectivity of these structures are evaluated by incorporating the
      PhCs as high reflective back mirrors in GaSb-based ridge waveguide lasers with
      cavity lengths between 200 and 1100 um with the front facet as cleaved. The
      shortest devices show remarkable threshold currents below 12 mA and efficiencies
      of 0.23 W A(-1), yielding a maximum output power of almost 19 mW, proving the
      applicability of the chosen approach to numerous further concepts based on 2D
      PhCs on the GaSb material system.

PMID- 21730526
TI  - Transparent and flexible thin-film transistors with channel layers composed of
      sintered HgTe nanocrystals.
AB  - Transparent and flexible thin film transistors (TFTs) with channel layers
      composed of sintered HgTe nanocrystals were fabricated on top of UV/ozone treated
      plastic substrates and their electrical properties were characterized. A
      representative TFT with a channel layer composed of sintered HgTe nanocrystals
      revealed typical p-type characteristics, an on/off current ratio of ~10(3) and a
      field-effect mobility of 4.1 cm(2) V(-1) s(-1). When the substrate was bent until
      the bending radius of the substrate reached 2.4 cm, which corresponded to a
      strain of 0.83% that the HgTe thin film experienced, the TFT exhibited an on/off
      current ratio of ~10(3) and a field-effect mobility of 4.0 cm(2) V(-1) s(-1).

PMID- 21730527
TI  - Directed self-assembly of quantum structures by nanomechanical stamping using
      probe tips.
AB  - We demonstrate that nanomechanically stamped substrates can be used as templates
      to pattern and direct the self-assembly of epitaxial quantum structures such as
      quantum dots. Diamond probe tips are used to indent or stamp the surface of
      GaAs(100) to create nanoscale volumes of dislocation-mediated deformation, which
      alter the growth surface strain. These strained sites act to bias nucleation,
      hence allowing for selective growth of InAs quantum dots. Patterns of quantum
      dots are observed to form above the underlying nanostamped template. The strain
      state of the patterned structures is characterized by micro-Raman spectroscopy.
      The potential of using nanoprobe tips as a quantum dot nanofabrication technology
      are discussed.

PMID- 21730528
TI  - Narrow linewidth templates for nanoimprint lithography utilizing conformal
      deposition.
AB  - Nanoimprint lithography has the potential to cost efficiently realize patterns
      with extremely narrow linewidth over a large area. A significant challenge to
      achieving this target is the fabrication of nanoimprint templates. The cost and
      writing time of conventional electron beam lithography for direct writing of the
      templates rapidly increases as the patterned area increases and the linewidth
      decreases. We have developed a novel process for creating narrow linewidth
      nanopatterns. This process is based on conformal deposition of thin films on seed
      nanopatterns. We have demonstrated the process by fabricating nanosized loops and
      lines. The linewidth of the structures can be tuned precisely, and in our
      experiments it could be reduced to 20 nm. The closed loop structures are
      interesting, since this geometry is crucially important in many leading edge
      research fields such as negative refractive index materials, ultrahigh density
      memory applications and quantum rings. The fabricated template was subsequently
      used as a template in soft-stamp UV nanoimprint lithography to successfully
      replicate the structures in UV-curable resist.

PMID- 21730529
TI  - Rapid fabrication of nanoneedle arrays by ion sputtering.
AB  - We report a novel method for rapidly fabricating ordered nanoneedles using an ion
      beam that cuts through the Fe/GaAs single thin layer or the Fe/MgO/Fe/GaAs
      multilayer producing a pillar pattern followed by raster-scanning normal to the
      patterned area. However, such ordered nanoneedles were not formed on the pure
      GaAs substrate surface without the thin Fe film coating, nor were nanoneedles
      formed on the GaAs substrate coated with a thin Cr epitaxial film, when this
      method was used. It has advantages over other methods, being simple, fast and
      well controlled for fabricating one-dimensional nanostructure arrays, leading to
      a range of applications such as high aspect ratio sharp tips for atomic force
      microscope/atom probes and consequent possible quantum confinement effects or
      arrays of nanostructures for field-optical/photoluminescence emission and data
      recording.

PMID- 21730530
TI  - Electrochemically replicated smooth aluminum foils for anodic alumina nanochannel
      arrays.
AB  - A fast electrochemical replication technique has been developed to fabricate
      large-scale ultra-smooth aluminum foils by exploiting readily available large
      scale smooth silicon wafers as the masters. Since the adhesion of aluminum on
      silicon depends on the time of surface pretreatment in water, it is possible to
      either detach the replicated aluminum from the silicon master without damaging
      the replicated aluminum and master or integrate the aluminum film to the silicon
      substrate. Replicated ultra-smooth aluminum foils are used for the growth of both
      self-organized and lithographically guided long-range ordered arrays of anodic
      alumina nanochannels without any polishing pretreatment.

PMID- 21730531
TI  - Fabrication and electrical properties of a Cu-tetracyanoquinodimethane nanowire
      array in a porous anodic alumina template.
AB  - A nanowire array of metal-organic complex copper-tetracyanoquinodimethane
      (CuTCNQ) was obtained by depositing a layer of copper in the bottom of anodic
      alumina template channels during a vapor-induced reaction method. SEM observation
      showed that the channel diameters of anodic alumina membranes prepared under 40 V
      and 200 V are about 60 nm and 200 nm, respectively, and CuTCNQ nanowire arrays
      were synthesized in these channels. Nanodevice prototypes with electrical
      switching characteristics based on a CuTCNQ nanowire array were fabricated, whose
      reproducible electrical switching and memory effects were observed. The on-off
      ratio for switching reaches 10(4). The potential applications in information
      storage devices are also discussed.

PMID- 21730532
TI  - Closed-form approximation and numerical validation of the influence of van der
      Waals force on electrostatic cantilevers at nano-scale separations.
AB  - In this paper the two-point boundary value problem (BVP) of the cantilever
      deflection at nano-scale separations subjected to van der Waals and electrostatic
      forces is investigated using analytical and numerical methods to obtain the
      instability point of the beam. In the analytical treatment of the BVP, the
      nonlinear differential equation of the model is transformed into the integral
      form by using the Green's function of the cantilever beam. Then, closed-form
      solutions are obtained by assuming an appropriate shape function for the beam
      deflection to evaluate the integrals. In the numerical method, the BVP is solved
      with the MATLAB BVP solver, which implements a collocation method for obtaining
      the solution of the BVP. The large deformation theory is applied in numerical
      simulations to study the effect of the finite kinematics on the pull-in
      parameters of cantilevers. The centerline of the beam under the effect of
      electrostatic and van der Waals forces at small deflections and at the point of
      instability is obtained numerically. In computing the centerline of the beam, the
      axial displacement due to the transverse deformation of the beam is taken into
      account, using the inextensibility condition. The pull-in parameters of the beam
      are computed analytically and numerically under the effects of electrostatic
      and/or van der Waals forces. The detachment length and the minimum initial gap of
      freestanding cantilevers, which are the basic design parameters, are determined.
      The results of the analytical study are compared with the numerical solutions of
      the BVP. The proposed methods are validated by the results published in the
      literature.

PMID- 21730533
TI  - Tin oxide nanocluster hydrogen and ammonia sensors.
AB  - We have prepared sensitive hydrogen and ammonia sensors from thin films of tin
      nanoclusters with diameters between 3 and 10 nm. By baking the samples at 200 
      degrees C in ambient air the clusters were oxidized, resulting in very stable
      films of tin oxide clusters with similar diameters to the original Sn clusters.
      By monitoring the electrical resistance, it is shown that the cluster films are
      highly responsive to hydrogen and ammonia at relatively low temperatures, thereby
      making them attractive for commercial applications in which low power consumption
      is required. Doping of the films by depositing Pd on top of the clusters resulted
      in much improved sensor response and response times. It is shown that optimal
      sensor properties are achieved for very thin cluster films (a few monolayers of
      clusters).

PMID- 21730534
TI  - A composite of polyelectrolyte-grafted multi-walled carbon nanotubes and in situ
      polymerized polyaniline for the detection of low concentration triethylamine
      vapor.
AB  - Multi-walled carbon nanotubes (MWNTs) grafted with sodium polystyrenesulfonate
      (NaPSS) were deposited on an interdigitated gold electrode decorated with a layer
      of positively charged poly(diallyldimethylammonium chloride) by a self-assembly
      method. Then polyaniline (PANI) was in situ polymerized on the surface of the
      MWNTs to prepare a composite. The structure and morphology of the composite were
      investigated by Raman spectroscopy and scanning electron microscopy. The
      electrical responses of the composite to triethylamine vapor of low
      concentrations were measured at room temperature. It was found that the composite
      exhibited a linear response to the vapor in the range of 0.5-8 ppm with the
      highest sensitivity of ~80%, which is much higher than that of MWNTs and PANI
      separately, and an obvious synergetic effect was observed. In addition, the
      detection limit was as low as the ppb level, and reversible and relatively fast
      responses (t(90%)~200 s and ~10 min for sensing and recovery, respectively) were
      observed. The sensing characteristics are highly related to the gas responses of
      PANI, and a sensing mechanism considering the interaction of MWNTs and PANI was
      proposed.

PMID- 21730535
TI  - Scaling laws for nanoFET sensors.
AB  - The sensitive conductance change of semiconductor nanowires and carbon nanotubes
      in response to the binding of charged molecules provides a novel sensing modality
      which is generally denoted as nanoFET sensors. In this paper, we study the
      scaling laws of nanoplate FET sensors by simplifying nanoplates as random
      resistor networks with molecular receptors sitting on lattice sites.
      Nanowire/tube FETs are included as the limiting cases where the device width goes
      small. Computer simulations show that the field effect strength exerted by the
      binding molecules has significant impact on the scaling behaviors. When the field
      effect strength is small, nanoFETs have little size and shape dependence. In
      contrast, when the field effect strength becomes stronger, there exists a lower
      detection threshold for charge accumulation FETs and an upper detection threshold
      for charge depletion FET sensors. At these thresholds, the nanoFET devices
      undergo a transition between low and large sensitivities. These thresholds may
      set the detection limits of nanoFET sensors, while they could be eliminated by
      designing devices with very short source-drain distance and large width.

PMID- 21730536
TI  - Designing spatial correlation of quantum dots: towards self-assembled three
      dimensional structures.
AB  - Buried two-dimensional arrays of InP dots were used as a template for the lateral
      ordering of self-assembled quantum dots. The template strain field can laterally
      organize compressive (InAs) as well as tensile (GaP) self-assembled
      nanostructures in a highly ordered square lattice. High-resolution transmission
      electron microscopy measurements show that the InAs dots are vertically
      correlated to the InP template, while the GaP dots are vertically anti
      correlated, nucleating in the position between two buried InP dots. Finite InP
      dot size effects are observed to originate InAs clustering but do not affect GaP
      dot nucleation. The possibility of bilayer formation with different vertical
      correlations suggests a new path for obtaining three-dimensional pseudocrystals.

PMID- 21730537
TI  - Temperature and excitation density dependent photoluminescence of sputtering
      induced GaAs/AlGaAs quantum dots.
AB  - GaAs/AlGaAs quantum dots (QDs) are fabricated by low-energy ion beam sputtering
      and molecular beam epitaxy (MBE) re-growth. Temperature (6.5-78 K) and excitation
      power density (0.49-3.06 W cm(-2)) dependent photoluminescence (PL) are presented
      and discussed in detail. The low-temperature PL emission at 720 nm is attributed
      to GaAs QDs with height of ~6.1 nm and base width of ~23 nm, calculated based on
      the quantum box model with infinite potential barrier. The calculated QD
      dimensions are in good agreement with those obtained from atomic force microscopy
      (AFM) analysis. Nonradiative recombination and Auger-assisted recombination are
      found to be the main PL quenching mechanisms at high temperature.

PMID- 21730538
TI  - A 'green' chitosan-silver nanoparticle composite as a heterogeneous as well as
      micro-heterogeneous catalyst.
AB  - In this paper, we report on the catalytic activity of a new metal nanoparticle
      polymer composite consisting of Ag nanoparticles (NPs) and environmentally
      friendly ('green') chitosan. The polymer (chitosan) not only acted as the
      reducing agent for the metal ions, but also stabilized the product NPs by
      anchoring them. The majority of the particles produced in this way had sizes less
      than 5 nm. The catalytic activity of the composite was investigated
      photometrically by monitoring the reduction of 4-nitrophenol (4NP) in the
      presence of excess NaBH(4) in water, under both heterogeneous and micro
      heterogeneous conditions. The reaction was first order with respect to the
      concentration of 4NP. We also observed that the apparent rate constant, k(app),
      for the reaction was linearly dependent on the amount of Ag NPs present in the
      composite. Moreover, the turn-over frequency (TOF) of the catalyst was found to
      be (1.5 +/- 0.3) * 10(-3) s(-1), when the reaction was carried out under
      heterogeneous conditions. The Ag NPs in the composite retained their catalytic
      activities even after using them for ten cycles. Our observations also suggest
      that the catalytic efficiency under micro-heterogeneous conditions is much higher
      than under heterogeneous conditions. Thus the composite we have represents an
      ideal case of an environmentally friendly and stable catalyst, which works under
      heterogeneous as well as micro-heterogeneous conditions with the advantage of
      nanoscopic particles as the catalyst.

PMID- 21730539
TI  - Electrospun nanofiber belts made from high performance copolyimide.
AB  - Electrospun nanofibers based on copolyimides were made, aiming at finding a
      promising method for improving the mechanical properties of electrospun polyimide
      nanofibers. The copolyimide had a backbone consisting of 3,3',4,4'-biphenyl
      tetracarboxylic dianhydride (BPDA), biphenylamide (BPA) and 4,4'-oxydianiline
      (ODA) residues. The structure and composition of the copolyimide was controlled
      by the ratio of rigid BPA and flexible ODA moieties. The electrospun copolyimide
      nanofibers were collected in the form of a belt using a rotating disc with a rim
      of 8 mm width. Scanning electron microscopy (SEM), infrared (IR) spectroscopy, x
      ray scattering and tensile testing, dynamic mechanical analysis (DMA) and
      thermogravimetric analysis (TGA) were used to characterize the nanofiber belts.
      The nanofibers had a diameter range from 80 to 300 nm and were well aligned in
      the belts. The thermal stability of the nanofiber belts was over 460  degrees C.
      The tensile test showed that the copolyimide nanofiber belts had much better
      mechanical properties than either of the flexible and rigid homo-polyimide (homo
      PI) nanofiber belts. The tensile strength, modulus and elongation to break of the
      copolyimide nanofiber belt with BPA/ODA ratio of 40/60 are respectively 1.1 +/-
      0.1 GPa, 6.2 +/- 0.7 GPa and 20.8 +/- 1.2%, compared to 459 +/- 36 MPa, 2.1 +/-
      0.3 GPa and 41.3 +/- 2.2% for BPDA/ODA homo-PI as well as 384 +/- 18 MPa, 11.5 +/
      0.6 GPa and 3.9 +/- 0.1% for BPDA/BPA homo-PI. The important feature is that the
      electrospun polymer nanofibers can be made very strong by using copolyimides as
      spinning materials.

PMID- 21730540
TI  - Spiral patterns of gold nanoclusters in silicon (100) produced by metal vapour
      vacuum arc implantation of gold ions.
AB  - Self-assembled gold nanoclusters are attractive building blocks for future
      nanoscale sensors and optical devices due to their exciting catalytic properties.
      In this work, we report direct bottom-up synthesis of spiral patterns of gold
      nanoclusters in silicon (100) substrates by Au ion implantation followed by
      thermal annealing. This unique phenomenon is observed only above a critical
      threshold implantation dose and annealing temperature. Systematic study by
      electron microscopy, analytical x-ray diffraction and atomic force microscopy
      shows the temperature- and time-dependent nucleation, growth of Au nanoclusters
      and evolution of the spiral patterns. The observed patterns of gold nanoclusters
      bear a resemblance to the spiral growth prevalent in some directionally
      solidified eutectic alloys. Based on this systematic study of the growth and
      morphology of nanoclusters, a tentative model has been proposed for the formation
      mechanism of this unusual self-assembled pattern in an amorphous Si/Au system.
      This model shows that melting of the implanted layer is essential and without
      which no spiral patterns are observed. A better understanding of this self
      assembly process will open up new ways to fabricate ordered arrays of gold
      nanoclusters in silicon substrates for seeding selective growth of one
      dimensional nanostructures.

PMID- 21730541
TI  - High-yield synthesis and optical response of gold nanostars.
AB  - Multipod Au nanoparticles (nanostars) with single crystalline tips were
      synthesized in extremely high yield through the reduction of HAuCl(4) in a
      concentrated solution of poly(vinylpyrrolidone) (PVP) in N,N-dimethylformamide
      (DMF), in the presence of preformed Au nanoparticle seeds, but with no need for
      external energy sources. Nanostar dispersions display a well-defined optical
      response, which was found (through theoretical modeling) to comprise a main mode
      confined within the tips and a secondary mode confined in the central body.
      Calculations of the surface enhanced Raman scattering (SERS) response
      additionally show that this morphology will be relevant for sensing applications.

PMID- 21730542
TI  - Gold nanoshell photomodification under a single-nanosecond laser pulse
      accompanied by color-shifting and bubble formation phenomena.
AB  - Laser-nanoparticle interaction is crucial for biomedical applications of lasers
      and nanotechnology to the treatment of cancer or pathogenic microorganisms. We
      report on the first observation of laser-induced coloring of gold nanoshell
      solution after a one nanosecond pulse and an unprecedentedly low bubble formation
      (as the main mechanism of cancer cell killing) threshold at a laser fluence of
      about 4 mJ cm(-2), which is safe for normal tissue. Specifically, silica/gold
      nanoshell (140/15 nm) suspensions were irradiated with a single 4 ns (1064 nm) or
      8 ns (900 nm) laser pulse at fluences ranging from 0.1 mJ cm(-2) to 50 J cm(-2).
      Solution red coloring was observed by the naked eye confirmed by blue-shifting of
      the absorption spectrum maximum from the initial 900 nm for nanoshells to 530 nm
      for conventional colloidal gold nanospheres. TEM images revealed significant
      photomodification of nanoparticles including complete fragmentation of gold
      shells, changes in silica core structure, formation of small 20-30 nm isolated
      spherical gold nanoparticles, gold nanoshells with central holes, and large and
      small spherical gold particles attached to a silica core. The time-resolved
      monitoring of bubble formation phenomena with the photothermal (PT) thermolens
      technique demonstrated that after application of a single 8 ns pulse at fluences
      5-10 mJ cm(-2) and higher the next pulse did not produce any PT response,
      indicating a dramatic decrease in absorption because of gold shell modification.
      We also observed a dependence of the bubble expansion time on the laser energy
      with unusually very fast PT signal rising (~3.5 ns scale at 0.2 J cm(-2)).
      Application of the observed phenomena to medical applications is discussed,
      including a simple visual color test for laser-nanoparticle interaction.

PMID- 21730543
TI  - Size-induced crystal field parameter change and tunable infrared luminescence in
      Ni(2+)-doped high-gallium nanocrystals embedded glass ceramics.
AB  - Transparent Ni(2+)-doped Li(2)O-Ga(2)O(3)-SiO(2) glass ceramics (GCs) were
      prepared and characterized. By controlling the size of the nanocrystals, the
      infrared luminescence is tunable. It could be ascribed to alteration of the
      crystal field strength Dq of octahedral Ni(2+), which is due to the changes of
      the lattice parameters. The change in optical signals at telecommunication bands
      when the seed beam passes through the bulk sample with or without 980 nm
      excitation was also demonstrated for the first time. The coefficient of the
      change in optical signals at 1.3 um is calculated as 0.26 cm(-1). The changes in
      optical signal have shown similar wavelength dependence on the luminescence
      property.

PMID- 21730544
TI  - Characteristics of domain wall pinning and depinning in a three-terminal magnetic
      Y-junction.
AB  - The characteristics of domain wall (DW) pinning and propagation in a three
      terminal magnetic Y-junction were investigated, where the junction consisted of
      two input and one output wires. The output switching depends strongly on the
      junction angle (alpha). Junctions with high angles of alpha>9.5 degrees  lead to
      DW pinning at the junction, whereas junctions with low angles of alpha<9.5
      degrees  have no DW pinning effect. At the critical angle of alpha = 9.5 degrees
      , the Y-junction showed a multimode DW propagation, which was ascribed to a
      moderate transverse field effect.

PMID- 21730545
TI  - Characterization of nanometer-sized, mechanically exfoliated graphene on the H
      passivated Si(100) surface using scanning tunneling microscopy.
AB  - We have developed a method for depositing graphene monolayers and bilayers with
      minimum lateral dimensions of 2-10 nm by the mechanical exfoliation of graphite
      onto the Si(100)-2 * 1:H surface. Room temperature, ultrahigh vacuum tunneling
      spectroscopy measurements of nanometer-sized single layer graphene reveal a size
      dependent energy gap ranging from 0.1 to 1 eV. Furthermore, the number of
      graphene layers can be directly determined from scanning tunneling microscopy
      topographic contours. This atomistic study provides an experimental basis for
      probing the electronic structure of nanometer-sized graphene which can assist the
      development of graphene-based nanoelectronics.

PMID- 21730546
TI  - Line edge roughness after development in a positive-tone chemically amplified
      resist of post-optical lithography investigated by Monte Carlo simulation and a
      dissolution model.
AB  - Line edge roughness (LER) of patterned features in chemically amplified (CA)
      resists is formed in the acid generation stage and expected to be moderated by
      the acid diffusion and development process. It is essential to obtain information
      on the limit of LER in order to realize next-generation lithographies such as
      electron beam or extreme ultraviolet. Here, we report for the first time a
      process simulator based on physical and chemical reaction mechanisms. The LER of
      a positive-tone CA resist after development is investigated by Monte Carlo
      simulation and Mack's dissolution model. We found that the LER (high frequency)
      of less than 1.2 nm is achievable, although the process conditions and material
      design for achieving such a small LER are strict.

PMID- 21730547
TI  - Preparation and characterization of CdS nanoparticles decorated into titanate
      nanotubes and their photocatalytic properties.
AB  - Nanoscopic CdS particles are decorated into the microchannel with nanometre-scale
      diameter of titanate nanotubes (TNTs) by using nonionic thioacetamide (TAA) as a
      sulfide precursor (labelled as CdS(TAA)/TNTs). The characterizations by XPS, TEM,
      XRD, Raman spectroscopy and UV-vis absorption confirm that CdS nanoparticles with
      smaller size and more homogeneous dispersion are obtained by using a TAA
      precursor in contrast to the particles predominantly formed on the surface of
      TNTs by adding ionic Na(2)S as a precursor (labelled as CdS(Na(2)S)/TNTs). As is
      expected, the photocatalytic activities of the nanosized CdS sensitized TNTs
      nanocrystal materials were superior to those of simple CdS and TNTs in the
      oxidation of rhodamine B under visible light irradiation. Furthermore, the
      comparison of photocatalysis activity between CdS(TAA)/TNTs and CdS(Na(2)S)/TNTs
      is also discussed.

PMID- 21730548
TI  - Highly active nanocrystalline TiO(2) photoelectrodes.
AB  - A simple method for the fabrication of highly photoactive nanocrystalline two
      layer TiO(2) electrodes for solar cell applications is presented. Diluted
      titanium acetylacetonate has been used as a precursor for covering SnO(2):F (FTO)
      films with dense packed TiO(2) nanocrystallites. The nanoporous thick TiO(2) film
      follows the dense packed thin TiO(2) film as a second layer. For the latter,
      amorphous TiO(2) nanoparticles have been successfully synthesized by a sol-gel
      technique in an acidic environment with pH<1 and hydrothermal growth at a
      temperature of 200  degrees C. The acidic nanoparticle gel was neutralized by
      basic ammonia and a TiO(2) gel of pH 5 was obtained; this pH value is higher than
      the recently reported value of 3.1 (Park et al 2005 Adv. Mater. 17 2349-53).
      Highly interconnected, nanoporous, transparent and active TiO(2) films have been
      fabricated from the pH 5 gel. SEM, AFM and XRD analyses have been carried out for
      investigation of the crystal structure and the size of nanoparticles as well as
      the surface morphology of the films. Investigation of the photocurrent-voltage
      characteristics has shown improvement in cell performance along with the
      modification of the surface morphology, depending on pH of the TiO(2) gel.
      Increasing the pH of the gel from 2.1 to 5 enhanced the overall conversion
      efficiency of the dye-sensitized solar cells by approximately 30%. An energy
      conversion efficiency of 8.83% has been achieved for the cell (AM1.5, 100  mWcm(
      2) simulated sunlight) compared to 6.61% efficiency in the absence of ammonia in
      the TiO(2) gel.

PMID- 21730549
TI  - Spatial fluctuations of optical emission from single ZnO/MgZnO nanowire quantum
      wells.
AB  - MgZnO/ZnO quantum wells on top of ZnO nanowires were grown by pulsed laser
      deposition. Ensembles of spatially fluctuating and narrow cathodoluminescence
      peaks with single widths down to 1 meV were found at the spectral position of the
      quantum well emission at 4 K. In addition, the number of these narrow QW peaks
      increases with increasing excitation power in micro-photoluminescence, thus
      pointing to quantum-dot-like emission centers. Indeed, laterally strained areas
      of about 5 nm diameter were identified at the quantum well positions on top of
      the nanowires by high-resolution transmission electron microscopy.

PMID- 21730550
TI  - Carbon nanotube Schottky diode: an atomic perspective.
AB  - The electron transport properties of semiconducting carbon nanotube (SCNT)
      Schottky diodes are investigated with atomic models using density functional
      theory and the non-equilibrium Green's function method. We model the SCNT
      Schottky diode as a SCNT embedded in the metal electrode, which resembles the
      experimental set-up. Our study reveals that the rectification behaviour of the
      diode is mainly due to the asymmetric electron transmission function distribution
      in the conduction and valence bands and can be improved by changing metal-SCNT
      contact geometries. The threshold voltage of the diode depends on the electron
      Schottky barrier height which can be tuned by altering the diameter of the SCNT.
      Contrary to the traditional perception, the metal-SCNT contact region exhibits
      better conductivity than the other parts of the diode.

PMID- 21730551
TI  - Real-time detection of linear and angular displacements with a modified DVD
      optical head.
AB  - Here we demonstrate that an astigmatic detection system (ADS), constructed with a
      modified digital-versatile-disk (DVD) optical head, can achieve real-time
      measurement of a linear displacement and two-dimensional (2D) tilt angles with a
      high sensitivity. An atomic force microscope (AFM), using our detection system to
      sense the deflection of microfabricated cantilevers, can resolve single atomic
      steps on graphite surfaces with a noise level less than 0.04 nm in topographic
      images. This astigmatic detection system can even detect mechanical resonances
      due to thermal vibrations of microfabricated cantilevers. The high sensitivity,
      small detecting size and high bandwidth of this detection system is suitable for
      dynamic characterization of elements in micromachined components. Further
      optimization of the system will promise many other applications in diverse
      technological fields.

PMID- 21730552
TI  - A photovoltaic device based on a poly(phenyleneethynylene)/SWNT composite active
      layer.
AB  - Although research on the use of single walled carbon nanotubes (SWNTs) as the
      acceptor in polymer photovoltaic cells is currently making great progress, their
      poor dispersion in a polymer matrix has greatly hindered the overall performance
      of the devices. Here a novel bulk heterojunction structure based on a
      poly(phenyleneethynylene)/SWNT composite was designed to improve the dispersion
      of SWNTs in the composite based on their structural similarity and strong
      interaction. Better dispersion and higher performance are achieved compared with
      a common control device based on a poly(3-octylthiophene)/SWNT composite layer.

PMID- 21730553
TI  - Magnetic-field-assisted solvothermal growth of single-crystalline bismuth
      nanowires.
AB  - The magnetic-field-assisted approach has been used in the shape-controlled
      synthesis of single Bi nanocrystals. By tuning the magnetic field strength in the
      solvothermal process, Bi nanowires with dimension of 40-200 nm and lengths up to
      tens of micrometers were synthesized. Various techniques such as x-ray
      diffraction, scanning electron microscopy, transmission electron microscopy and
      Fourier transform infrared spectrometry have been used to characterize the
      products obtained. The results show that the magnetic field plays a key role in
      the crystal growth of the Bi nanowires. All nanowires were highly oriented single
      crystals with the growth direction along the c-axis.

PMID- 21730554
TI  - Pulsed co-electrodeposition and characterization of Ni-based nanocomposites
      reinforced with combustion-synthesized, undoped, tetragonal-ZrO(2) particulates.
AB  - Nanostructured nickel matrix composites reinforced with nanosized, undoped,
      tetragonal zirconia has been synthesized by cathodic pulsed electrodeposition.
      The reinforcement is synthesized by the aqueous combustion synthesis route with
      glycine as the fuel and zirconyl nitrate as the oxidizer. The reinforcement and
      composite have been characterized by XRD, TEM and SEM coupled with EDS. The
      microhardness and thermal stability (Kissinger method) of the composite are
      evaluated. These values are compared with those of pure nickel deposited under
      the same conditions. The results show that the microhardness of the nickel matrix
      is enhanced by the presence of the reinforcement from 450 to 575 VHN. Also the
      strengthening due to grain size effects and dispersion strengthening effect are
      evaluated individually and the interparticle separation is estimated to be around
      85 nm. The volume fraction of the reinforcement is estimated to be 12-15% and the
      particles are uniformly distributed and monodispersed in the nickel matrix. The
      thermal stability of the composite is better than that of pure nickel in contrast
      to some of the reported literature.

PMID- 21730555
TI  - Type I collagen-templated assembly of silver nanoparticles and their application
      in surface-enhanced Raman scattering.
AB  - Silver nanoparticles (Ag NPs) are one of the active substrates that are employed
      extensively in surface-enhanced Raman scattering (SERS), and aggregations of Ag
      NPs play an important role in enhancing the Raman signals. In this paper, we
      fabricated two kinds of SERS-active substrates utilizing the electrostatic
      adsorption and superior assembly properties of type I collagen. These were
      collagen-Ag NP aggregation films and nanoporous Ag films. Two probe molecules, 4
      aminothiophenol (4-ATP) and methylene blue (MB), were studied on these
      substrates. These substrates showed reproducible SERS intensities with relative
      standard deviations (RSDs) of 8-10% and 11-14%, respectively, while the RSDs of
      the traditional thick Ag films were 12-28%. Also, the intensities for the 4-ATP
      spectrum on the collagen-templated nanoporous Ag film were approximately one
      order higher than those on the DNA-templated Ag film.

PMID- 21730556
TI  - Preparation of water-soluble multi-walled carbon nanotubes by polymer dispersant
      assisted exfoliation.
AB  - Water-soluble multi-walled carbon nanotubes (MWNTs) with a high solubility of
      29.2 mg ml(-1) were obtained by polymer dispersant hydrolyzed poly(styrene-co
      maleic anhydride) (HSMA) assisted exfoliation and centrifugation. The MWNTs were
      exfoliated and dispersed in aqueous solution by non-covalent modification with
      polymer dispersant of HSMA. Characterizations of HSMA-coated MWNTs were conducted
      via transmission electron microscopy (TEM), UV-vis and fluorescence spectroscopy,
      and thermal gravimetric analysis (TGA). The as-prepared HSMA-coated MWNTs showed
      good dispersibility and stability in water.

PMID- 21730557
TI  - XPS studies of DNA-cation-interacted self-assembled HgTe quantum dots formed
      under electrodeposition and their resultant biomolecular recognition application.
AB  - DNA interactions with multivalent cations, leading to wrapping around the cations
      and thermodynamically stable structure formation, followed by electrodeposition,
      have yielded a narrow size distributed single-crystalline HgTe-DNA quantum dot
      (QD) hybrid system. The mechanisms of the DNA interactions resulting in self
      assembled HgTe QDs through phosphate-cation linkages and superstructure formation
      by nitrogen base interactions have been established by their respective binding
      energy shifts as evidenced from x-ray photoelectron spectroscopic studies. The
      photoluminescence peak position associated with HgTe QD single stranded DNA is
      red shifted in the presence of its conjugate and suggests the system as a
      potential optical probe for biomolecular recognition applications.

PMID- 21730558
TI  - Reversible, reagentless solubility changes in phosphatidylcholine-stabilized gold
      nanoparticles.
AB  - Phosphatidylcholine (PC) is a versatile ligand for synthesizing gold
      nanoparticles that are soluble in either organic or aqueous media. Here we report
      a novel route to organic-soluble, PC-stabilized gold nanoparticles that can be re
      suspended in water after removal of the organic solvent. Similarly, we show that
      PC-stabilized gold nanoparticles synthesized in water can be re-suspended in
      organic solvents after complete removal of water. Without complete removal of the
      solvent, the nanoparticles retain their original solubility and do not phase
      transfer. This change in solvent preference from organic to aqueous and vice
      versa without the use of an additional phase transfer reagent is novel, visually
      striking, and of utility for synthetic modification of nanoparticles. This
      approach allows chemical reactions to be performed on nanoparticles in organic
      solvents followed by conversion of the products to water-soluble materials. A
      narrow distribution of PC-stabilized gold nanoparticles was obtained after phase
      transfer to water as characterized by UV-visible (UV-vis) spectroscopy and
      transmission electron microscopy (TEM), demonstrating that the narrow
      distribution obtained from the organic synthesis is retained after transfer to
      water. This method produces water-soluble nanoparticles with a narrower
      dispersity than is possible with direct aqueous synthesis.

PMID- 21730559
TI  - Virus-mediated FCC iron nanoparticle induced synthesis of uranium dioxide
      nanocrystals.
AB  - A reducing system involving M13 virus-mediated FCC Fe nanoparticles was employed
      to achieve uranium reduction and synthesize uranium dioxide nanocrystals. Here we
      show that metastable face-centered cubic (FCC) Fe nanoparticles were fabricated
      around the surface of the M13 virus during the specific adsorption of the virus
      towards Fe ions under a reduced environment. The FCC phase of these Fe
      nanoparticles was confirmed by careful TEM characterization. Moreover, this virus
      mediated FCC Fe nanoparticle system successfully reduced contaminable U(VI) into
      UO(2) crystals with diameters of 2-5 nm by a green and convenient route.

PMID- 21730560
TI  - AlN nanorod and nanoneedle arrays prepared by chloride assisted chemical vapor
      deposition for field emission applications.
AB  - Hexagonal AlN nanorod and nanoneedle arrays were synthesized through the direct
      reaction of AlCl(3) and NH(3) by chemical vapor deposition at about 750  degrees
      C. Both the AlN nanoneedle and nanorod samples were of wurtzite structure and
      grew preferentially along the c-axis. With an increase in the ratio of NH(3) to
      Ar, an evolution from nanorods to nanoneedles was observed. A growth model was
      proposed to explain the possible growth mechanism. Measurements in field emission
      show that AlN nanoneedle arrays have a much lower turn-on field (3.1 V um(-1))
      compared to nanorod arrays (15.3 V um(-1)), due to their large curvature
      geometry. The AlN nanoneedle arrays have potential applications in many fields,
      such as electron-emitting nanodevices and field-emission-based flat-panel
      displays.

PMID- 21730561
TI  - A study of the estimation method of the cutting force for a conical tool under
      nanoscale depth of cut by molecular dynamics.
AB  - This study uses molecular dynamics to simulate the nanoscale cutting of a Cu
      single crystal by a conical diamond tool. Actual nanoscale straight-line cutting
      experiments were performed, and the experimental results are compared with the
      simulation results. The heaping of copper atoms is qualitatively quite consistent
      with the simulation result. This paper also proposes a nanoscale contact pressure
      factor (NCP factor) that is applicable to the probes at different tip radii. An
      estimation model of the cutting force for nanoscale cutting is established. This
      model can estimate the cutting force during actual nanoscale cutting. Actual
      nanoscale cutting experiments were performed for verification, and the difference
      between the cutting force estimated by this model and the actual force is very
      small.

PMID- 21730562
TI  - Recombination dynamics in CdTe/CdSe type-II quantum dots.
AB  - Recombination dynamics in CdTe/CdSe core-shell type-II quantum dots (QDs) has
      been investigated by time-resolved photoluminescence (PL) spectroscopy. A very
      long PL decay time of several hundred nanoseconds has been found at low
      temperature, which can be rationalized by the spatially separated electrons and
      holes occurring in a type-II heterostructure. For the temperature dependence of
      the radiative lifetime, the linewidth and the peak energy of PL spectra show that
      the recombination of carriers is dominated by delocalized excitons at
      temperatures below 150 K, while the mixture of delocalized excitons, electrons
      and holes overwhelms the process at higher temperature. The binding energy of
      delocalized excitons obtained from the temperature dependence of the non
      radiative lifetime is consistent with the theoretical value. The energy
      dependence of lifetime measurements reveals a third power relationship between
      the radiative lifetime and the radius of QDs, the light of which can be shed by
      the quantum confinement effect. In addition, the radiative decay rate is found to
      be proportional to the square root of excitation power, arising from the change
      of wavefunction overlap of electrons and holes due to the band bending effect,
      which is an inherent character of a type-II band alignment.

PMID- 21730563
TI  - Anomalous high pressure behaviour in nanosized rare earth sesquioxides.
AB  - We report Raman spectroscopic studies of the nanosized rare earth sesquioxides,
      namely yttrium sesquioxide (Y(2)O(3)), gadolinium sesquioxide (Gd(2)O(3)) and
      samarium sesquioxide (Sm(2)O(3)), under high pressure. The samples were
      characterized using x-ray diffraction, Raman spectroscopy and atomic force
      microscopy at atmospheric pressures. Y(2)O(3) and Gd(2)O(3) were found to be
      cubic at ambient, while Sm(2)O(3) was found to be predominantly cubic with a
      small fraction of monoclinic phase. The strongest Raman peaks are observed at
      379, 344 and 363 cm(-1), respectively, for Y(2)O(3), Sm(2)O(3) and Gd(2)O(3). All
      the samples were found to be nanosized with 50-90 nm particle sizes. The high
      pressures were generated using a Mao-Bell type diamond anvil cell and a
      conventional laser Raman spectrometer is used to monitor the pressure-induced
      changes. Y(2)O(3) seems to undergo a crystalline to partial amorphous transition
      when pressurized up to about 19 GPa, with traces of hexagonal phase. However, on
      release of pressure, the hexagonal phase develops into the dominant phase.
      Gd(2)O(3) is also seen to develop into a mixture of amorphous and hexagonal
      phases on pressurizing. However, on release of pressure Gd(2)O(3) does not show
      any change and the transformation is found to be irreversible. On the other hand,
      Sm(2)O(3) shows a weakening of cubic phase peaks while monoclinic phase peaks
      gain intensity up to about a pressure of 6.79 GPa. However, thereafter the
      monoclinic phase peaks also reduce in intensity and mostly disordering sets in
      which does not show significant reversal as the pressure is released. The results
      obtained are discussed in detail.

PMID- 21730564
TI  - Quantized electron states in nearly depleted hexagonal nanowires.
AB  - The hexagonal quantum well (QW) is studied as a model for hexagonal nanowires,
      and the effects of donor impurities and geometrical deformations of the well are
      treated. By use of the Poisson equation the donor potential is calculated and the
      eigenspectrum of the hexagonal QW is shown to converge to that of a paraboloid
      quantum well with increasing donor density. Small deformations of the hexagon are
      shown to change the eigenspectrum significantly and give strong splittings of
      degenerate eigenvalues. Analytical approximations for the potential and
      eigenfunctions on the deformed hexagons are given.

PMID- 21730565
TI  - Nanoscale void nucleation and growth and crack tip stress evolution ahead of a
      growing crack in a single crystal.
AB  - A constrained three-dimensional atomistic model of a cracked aluminum single
      crystal has been employed to investigate the growth behavior of a nanoscale crack
      in a single crystal using molecular dynamics simulations with the EAM potential.
      This study is focused on the stress field around the crack tip and its evolution
      during fast crack growth. Simulation results of the observed nanoscale fracture
      behavior are presented in terms of atomistic stresses. Major findings from the
      simulation results are the following: (a) crack growth is in the form of void
      nucleation, growth and coalescence ahead of the crack tip, thus resembling that
      of ductile fracture at the continuum scale; (b) void nucleation occurs at a
      certain distance ahead of the current crack tip or the forward edge of the
      leading void ahead of the crack tip; (c) just before void nucleation the mean
      atomic stress (or equivalently its ratio to the von Mises effective stress, which
      is called the stress constraint or triaxiality) has a high concentration at the
      site of void nucleation; and (d) the stress field ahead of the current crack tip
      or the forward edge of the leading void is more or less self-similar (so that the
      forward edge of the leading void can be viewed as the effective crack tip).

PMID- 21730566
TI  - Dipole polarizability of onion-like carbons and electromagnetic properties of
      their composites.
AB  - Onion-like carbons (OLC) obtained by thermal transformation of nanodiamonds are
      agglomerates of multi-shell fullerenes, often covered by an external graphitic
      mantle. For the present work, elemental OLC units were constructed on the
      computer by coalescence of several two-layer fullerenes, in a structure similar
      to carbon peapods with a corrugated external wall. The electrical polarizability
      of such pod-of-peas fullerenes has been computed by a classical monopole-dipole
      atomistic theory. The description of pod-of-peas fullerenes was further
      simplified by representing them as linear arrays of point-like objects, whose
      polarizability matches that of the starting molecules. Calculations demonstrated
      that the static polarizability of spherically shaped assemblies of these arrays,
      modeling real OLC materials, is weakly dependent on the geometry of its
      constituent molecules and is chiefly proportional to the volume of the whole
      cluster. It increases with increasing filling fraction of the pod-of-peas
      fullerenes in the OLC aggregate. The polarizability so obtained can be used in
      Maxwell-Garnett theory to predict the permittivity of OLC-based composites, at
      least for static excitations. Experimental results obtained at GHz frequencies
      reveal a weak attenuation for OLC- and nanodiamond-based polydimethylsiloxane
      composites. In these silicone composites, we did not find long chains of coupled
      OLCs. Quite separated clusters were found instead, which contribute little to the
      polarizability and to the dielectric properties, in good agreement with our
      theoretical predictions.

PMID- 21730567
TI  - Evidence of localized amorphous silicon clustering from Raman depth-probing of
      silicon nanocrystals in fused silica.
AB  - Silicon nanocrystals (Si-nc) and amorphous silicon (alpha-Si) produced by silicon
      implantation in fused silica have been studied by micro-Raman spectroscopy.
      Information regarding the Raman signature of the alpha-Si phonon excitation was
      extracted from Raman depth-probing measurements using the phenomenological phonon
      confinement model. The spectral deconvolution of the Raman measurements recorded
      at different laser focusing depths takes into account both the Si-nc size
      variation and the Si-nc spatial distribution within the sample. The phonon peak
      associated with alpha-Si around 470 cm(-1) is greatest for in-sample laser
      focusing, indicating that the formation of amorphous silicon is more important in
      the region containing a high concentration of silicon excess, where large Si-nc
      are located. As also observed for Si-nc systems prepared by SiO(x) layer
      deposition, this result demonstrates the presence of alpha-Si in high excess Si
      implanted Si-nc systems.

PMID- 21730568
TI  - Fault-tolerant sub-lithographic design with rollback recovery.
AB  - Shrinking feature sizes and energy levels coupled with high clock rates and
      decreasing node capacitance lead us into a regime where transient errors in logic
      cannot be ignored. Consequently, several recent studies have focused on feed
      forward spatial redundancy techniques to combat these high transient fault rates.
      To complement these studies, we analyze fine-grained rollback techniques and show
      that they can offer lower spatial redundancy factors with no significant impact
      on system performance for fault rates up to one fault per device per ten million
      cycles of operation (P(f) = 10(-7)) in systems with 10(12) susceptible devices.
      Further, we concretely demonstrate these claims on nanowire-based programmable
      logic arrays. Despite expensive rollback buffers and general-purpose,
      conservative analysis, we show the area overhead factor of our technique is
      roughly an order of magnitude lower than a gate level feed-forward redundancy
      scheme.

PMID- 21730569
TI  - Preparation, characterization and photocatalytic properties of CdS nanoparticles
      dotted on the surface of carbon nanotubes.
AB  - Cadmium sulfide (CdS) nanoparticles dotted on the surface of multiwalled carbon
      nanotubes (MWCNTs) have been synthesized by the polyol method. The as-prepared
      materials were characterized by x-ray powder diffraction, transmission electron
      microscopy, scanning electron microscopy, and Brunauer-Emmett-Teller adsorption
      analysis. The results indicate that CdS nanoparticles with diameter of 5-8 nm are
      thickly and uniformly coated on the surface of the MWCNTs. The photodegradation
      of azo dye using these materials was evaluated by the degradation of Brilliant
      Red X-3B under visible light. The coated nanotubes show higher photocatalytic
      activity than both CdS alone and a CdS/activated carbon sample; in addition,
      there is an optimum content of MWCNTs. The presence of MWCNTs can also hamper the
      photocorrosion of CdS. The mechanism for the enhancement of MWCNTs on the
      adsorption and photocatalytic property of CdS is investigated for the first time.

PMID- 21730570
TI  - The fabrication of carbon nanostructures using electron beam resist pyrolysis and
      nanomachining processes for biosensing applications.
AB  - We present a facile, yet versatile carbon nanofabrication method using electron
      beam lithography and resist pyrolysis. Various resist nanopatterns were
      fabricated using a negative electron beam resist, SAL-601, and they were then
      subjected to heat treatment in an inert atmosphere to obtain carbon nanopatterns.
      Suspended carbon nanostructures were fabricated by the wet-etching of an
      underlying sacrificial oxide layer. Free-standing carbon nanostructures, which
      contain 130 nm wide, 15 nm thick, and 4 um long nanobridges, were fabricated by
      resist pyrolysis and nanomachining processes. Electron beam exposure dose effects
      on resist thickness and pattern widening were studied. The thickness of the
      carbon nanostructures was thinned down by etching with oxygen plasma. An
      electrical biosensor utilizing carbon nanostructures as a conducting channel was
      studied. Conductance modulations of the carbon device due to streptavidin-biotin
      binding and pH variations were observed.

PMID- 21730571
TI  - Manipulation and light-induced agglomeration of carbon nanotubes through optical
      trapping of attached silver nanoparticles.
AB  - A simple experimental method has been demonstrated for manipulating multi-walled
      carbon nanotube (MWCNT) bundles through the optical trapping of attached silver
      nanoparticles (SNPs). In our experiments, without the SNPs, the MWCNTs cannot be
      trapped due to their irregular shapes and large aspect ratio. However, when mixed
      with SNPs, the MWCNTs can be successfully trapped along with the SNPs using a
      TEM(00) mode laser at 532 nm. This is attributed to the optical trapping of the
      SNPs and attractive interaction or binding between the SNPs and MWCNTs due to
      electrostatic and van der Waals forces. Therefore, optical manipulation of MWCNT
      bundles is achieved through the manipulation of the attached silver
      nanoparticles/aggregates. In addition, we have observed the phenomenon of light
      induced further agglomeration of SNPs/MWCNTs which could potentially be exploited
      for fabricating patterned MWCNT films for future nanoscale devices and other
      applications.

PMID- 21730572
TI  - A large-area hybrid metallic nanostructure array and its optical properties.
AB  - A process for fabricating a large-area hybrid metallic nanostructure array is
      presented. The structures consist of an array of metal capped dielectric
      nanopillars and an array of metallic holes, each possessing its individual
      optical properties. The plasmon response of such structures can be viewed as the
      collection of plasmons from two geometries to form an interacting system.
      Experimental results show two peak values in the extinction spectrum for p
      polarized incident light. The two peaks in the extinction spectrum were shifted
      to longer wavelength and shorter wavelength respectively with the addition of
      absolute ethanol on the structure surface. The narrowest extinction peak appears
      at normal incidence.

PMID- 21730573
TI  - Memory effect in a junction-like CdS nanocomposite/conducting polymer poly[2
      methoxy-5-(2-ethylhexyloxy)1,4-phenylene-vinylene] heterostructure.
AB  - The operation of a nonvolatile memory device is demonstrated using junction-like
      CdS nanocomposites embedded in a polymer matrix. The capacitance-voltage
      characteristics of Al/conducting polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4
      phenylene-vinylene]/CdS nanocomposites in a polyvinyl alcohol matrix/indium tin
      oxide device exhibit hysteresis, which is attributed to the trapping, storage,
      and emission of holes in the quantized valence band energy levels of isolated CdS
      nanoneedles. The characteristics at different operating frequencies show that the
      hysteresis is due to trapping of charge carriers in CdS nanocomposites rather
      than in the interfacial states. The memory behavior in the inorganic/organic
      heterostructure is explained on the basis of a simple energy band diagram.

PMID- 21730574
TI  - Stable field emission from arrays of vertically aligned free-standing metallic
      nanowires.
AB  - We present a fully elaborated process to grow arrays of metallic nanowires with
      controlled geometry and density, based on electrochemical filling of nanopores in
      track-etched templates. Nanowire growth is performed at room temperature,
      atmospheric pressure and is compatible with low cost fabrication and large
      surfaces. This technique offers an excellent control of the orientation, shape
      and nanowires density. It is applied to fabricate field emission arrays with a
      good control of the emission site density. We have prepared Co, Ni, Cu and Rh
      nanowires with a height of 3 um, a diameter of 80 nm and a density of ~10(7) cm(
      2). The electron field emission measurements and total energy distributions show
      that the as-grown nanowires exhibit a complex behaviour, first with emission
      activation under high field, followed by unstable emission. A model taking into
      account the effect of an oxide layer covering the nanowire surface is developed
      to explain this particular field emission behaviour. Finally, we present an in
      situ cleaning procedure by ion bombardment that collectively removes this oxide
      layer, leading to a stable and reproducible emission behaviour. After treatment,
      the emission current density is ~1 mA cm(-2) for a 30 V um(-1) applied electric
      field.

PMID- 21730575
TI  - Periodically twinned SiC nanowires.
AB  - Twinning has been recognized to be an important microstructural defect in
      nanoscale materials. Periodically twinned SiC nanowires were largely synthesized
      by the carbothermal reduction of a carbonaceous silica xerogel prepared from
      tetraethoxysilane and biphenyl with iron nitrate as an additive. The twinned beta
      SiC nanowires, with a hexagonal cross section, a diameter of 50-300 nm and a
      length of tens to hundreds of micrometers, feature a zigzag arrangement of
      periodically twinned segments with a rather uniform thickness along the entire
      growth length. Computer simulation has been used to generate three-dimensional
      atomic structures of the zigzag columnar twin structure by the stacking of
      hexagonal discs of {111} planes of SiC. A minimum surface energy and strain
      energy argument is proposed to explain the formation of periodic twins in the SiC
      nanowires. The thickness of the periodic twinned segments is found to be linearly
      proportional to the nanowire diameter, and a constant volume model is proposed to
      explain the relation.

PMID- 21730576
TI  - The nanostructured phase transition of superhard Ti-Si-C-N coatings.
AB  - Ti-Si-C-N coatings with different Si contents were synthesized by means of pulsed
      direct current plasma-enhanced chemical vapor deposition using a TiCl(4),
      SiCl(4), CH(4), N(2), H(2) and Ar gas mixture. A complex phase transition has
      been identified which is strongly controlled by the silicon content in the
      coatings. Transmission electron microscopy (TEM) and x-ray diffraction (XRD)
      results indicate that increasing Si content leads to a phase transition from a
      solid solution (Ti, Si)(C, N) to a dual-phase Ti (C,N)+TiSi(2) structure, and
      then to a two-phase Ti (C,N)+SiC structure, and that the changes in grain size
      and lattice parameter coincide with the phase transition. The Ti-Si-C-N coatings
      with high Si contents (>=4.3 at.%) possess a superhigh hardness (43-52 GPa) due
      to grain refinement/grain boundary hardening and compressive stress/dispersion
      hardening of the hard, nanosized crystalline TiSi(2) or SiC dispersed in the
      matrix.

PMID- 21730577
TI  - The preparation of highly water-soluble multi-walled carbon nanotubes by
      irreversible noncovalent functionalization with a pyrene-carrying polymer.
AB  - Multi-walled carbon nanotubes (MWNTs) have been solubilized in water via a
      noncovalent method of exfoliation and centrifugation cycles with the assistance
      of hydrolyzed poly(styrene-co-maleic anhydride) carrying pyrene (HPSMAP). After
      the obtained solution was micro-filtered and dried, a water-soluble complex of
      HPSMAP-MWNTs was obtained. The solubility of HPSMAP-MWNTs was measured to be 46.2
      mg ml(-1) with a net MWNT concentration of 7.4 mg ml(-1) in water. Thermal
      gravimetric analyses showed that there was a large amount of polymer remaining on
      the surface of MWNTs irreversibly after thoroughly removing the free polymer.
      Other characterizations using transmission electron microscopy, Fourier transform
      infrared (FTIR) spectroscopy, fluorescence spectra, and fluorescence decay were
      conducted.

PMID- 21730578
TI  - Epitaxial growth of tungsten nanoparticles on alumina and spinel surfaces.
AB  - Isolated tungsten nanoparticles (alpha-W and beta-W phase) were synthesized and
      epitaxially grown on alumina and spinel particle surfaces with an average
      tungsten size of <=20 nm for a low tungsten content (of <=1.5 vol%). Using
      tungsten (VI) ethoxide alcoholic solutions, tungsten trioxide hydrated precursors
      were attached to a ceramic grains surface as a nanoparticle coating. High
      resolution transmission electron microscopy (HRTEM) micrographs showed epitaxial
      interfaces between alumina, spinel and metallic tungsten. This epitaxial growth
      is assumed to be due to the effect of water vapour on the sublimation of ortho
      tungstic acid during the reduction process in a hydrogen atmosphere. The planes
      involved in the epitaxy were found to be [Formula: see text] and [Formula: see
      text].

PMID- 21730579
TI  - Domain and network aggregation of CdTe quantum rods within Langmuir-Blodgett
      monolayers.
AB  - Control over the organization of quantum rods was demonstrated by changing the
      surface area at the air-liquid interface by means of the Langmuir-Blodgett (LB)
      technique. The LB isotherm of CdTe quantum rods capped with a mixture of
      alkylphosphines shows a transition point in the liquid-solid state, which is
      caused by the inter-rod reorganization. As we observed, at low surface pressure
      the quantum rods are assembled into round-shaped aggregates composed of a
      monolayer of nanorods packed in limited-size clusters with random orientation.
      The increase of the surface pressure leads to the rearrangement of these
      aggregates into elongated bundles composed of uniformly oriented nanorod
      clusters. Further compression results in denser packing of nanorods aggregates
      and in the transformation of monolayered domains into a continuous network of
      locally ordered quantum rods.

PMID- 21730580
TI  - The electrical properties of polymer nanocomposites with carbon nanotube fillers.
AB  - The electrical properties of polymer nanocomposites containing a small amount of
      carbon nanotube (CNT) are remarkably superior to those of conventional electronic
      composites. Based on three-dimensional (3D) statistical percolation and 3D
      resistor network modeling, the electrical properties of CNT nanocomposites, at
      and after percolation, were successfully predicted in this work. The numerical
      analysis was also extended to investigate the effects of the aspect ratio, the
      electrical conductivity, the aggregation and the shape of CNTs on the electrical
      properties of the nanocomposites. A simple empirical model was also established
      based on present numerical simulations to predict the electrical conductivity in
      several electronic composites with various fillers. This investigation further
      highlighted the importance of theoretical and numerical analyses in the
      exploration of basic physical phenomena, such as percolation and conductivity in
      novel nanocomposites.

PMID- 21730581
TI  - Light depolarization induced by metallic tips in apertureless near-field optical
      microscopy and tip-enhanced Raman spectroscopy.
AB  - We have investigated the depolarization effects of light scattered by sharp tips
      used for apertureless near-field optical microscopy. Dielectric and metal coated
      tips have been investigated and depolarization factors between 5 and 30% have
      been measured, changing as a function of the incident light polarization and of
      the tip shape. The experimental results are in good agreement with theoretical
      calculations performed by the finite element method, giving a near-field
      depolarization factor close to 10%. The effect of depolarization has been
      investigated in polarized tip-enhanced Raman spectroscopy (TERS) experiments; the
      depolarization gives rise to forbidden Raman modes in Si crystals.

PMID- 21730582
TI  - Doping effects of Co(2+) ions on ZnO nanorods and their photocatalytic
      properties.
AB  - A series of Zn(1-x)Co(x)O nanorods with dopant content ranging from x = 0.00 to
      0.10 was prepared by a wet chemical method. All Zn(1-x)Co(x)O samples were
      investigated by x-ray diffraction, transmission electron microscopy, energy
      dispersion x-ray line mapping analysis, and UV-visible absorption spectroscopy.
      It was found that Co(2+) ions were homogeneously substituted for Zn(2+) ions in
      ZnO nanorods. Rhodamine B degradation was used as a probe reaction to evaluate
      the effect of Co(2+) doping on ZnO nanorods and photocatalytic performance under
      UV light and visible light irradiation. Co(2+) ions acted as the trapping or
      recombination centers for electrons and holes, leading to a reduction in
      photodegradation efficiency under UV light illumination. Alternatively, Co(2+)
      ions enhanced the optical absorption and produced the photoinduced carriers under
      visible illumination in terms of two charge transfer transitions involving Co(2+)
      ions. Consequently, Co(2+) ions substituted in the lattice of ZnO nanorods
      significantly improved the visible light photocatalytic activity.

PMID- 21730583
TI  - Enhancement in dye-sensitized solar cells based on MgO-coated TiO(2) electrodes
      by reactive DC magnetron sputtering.
AB  - A surface modification method was carried out by reactive DC magnetron sputtering
      to fabricate TiO(2) electrodes coated with insulating MgO for dye-sensitized
      solar cells. The MgO-coated TiO(2) electrode had been characterized by x-ray
      photoelectron spectroscopy (XPS), energy-dispersive x-ray spectroscopy (EDX),
      scanning electron microscopy (SEM), UV-vis spectrophotometer, cyclic voltammetry
      (CV) and electrochemical impedance spectroscopy (EIS). The study results revealed
      that the TiO(2) modification increases dye adsorption, decreases trap states and
      suppresses interfacial recombination. The effects of sputtering MgO for different
      times on the performance of DSSCs were investigated. It indicated that sputtering
      MgO for 3 min on TiO(2) increases all cell parameters, resulting in increasing
      efficiency from 6.45% to 7.57%.

PMID- 21730584
TI  - Sr-hexaferrite/maghemite composite nanoparticles-possible new mediators for
      magnetic hyperthermia.
AB  - Composite nanoparticles with variable ratios of M-type Sr-hexaferrite and
      maghemite phases were prepared via the sol-gel method employing polyvinylalcohol
      as the stabilizing agent, followed by thermal treatment at 600  degrees C for 32
      190 min. The measurements in static magnetic field revealed considerable
      variation of the coercivity and remanence depending on the relative content of
      the highly magnetically anisotropic Sr-hexaferrite phase. Calorimetric heating
      experiments were carried out on aqueous gel suspensions under an alternating
      magnetic field of maximum amplitude H(max) = 15.1-68.4 kA m(-1) and frequency nu
      = 108 kHz. They showed a strong dependence of the heating efficiency on the
      coercivity and remanence of the composites, with a specific absorption rate (SAR)
      value ranging from units to tens of W/g(Fe(ferrimagnetic)).

PMID- 21730585
TI  - Carbon nanotube thermal interface material for high-brightness light-emitting
      diode cooling.
AB  - Aligned carbon nanotube (CNT) arrays were fabricated from a multilayer catalyst
      configuration by microwave plasma-enhanced chemical vapor deposition (PECVD). The
      effects of the thickness and annealing of the aluminum layer on the CNT synthesis
      and thermal performance were investigated. An experimental study of thermal
      resistance across the CNT array interface using the modified ASTM D5470 standard
      was conducted. It was demonstrated that the CNT-thermal interface material (CNT
      TIM) reduced the thermal interfacial resistance significantly compared with the
      state-of-art commercial TIM. The optimized thermal resistance of the CNT arrays
      is as low as 7 mm(2) K W(-1). The light performance of high-brightness light
      emitting diode (HB-LED) packages using the aligned CNT-TIM was tested. The
      results indicated that the light output power was greatly improved with the use
      of the CNT-TIM. The usage of the CNT-TIM can be also extended to other
      microelectronics thermal management applications.

PMID- 21730586
TI  - Oscillation of gas molecules in carbon nanotubes.
AB  - The dynamics of N(2) molecules blocked in open single-walled carbon nanotubes is
      investigated using molecular dynamics simulations. It is found that periodic
      axial and radial oscillations with extremely high frequency exist widely among
      these molecules. Between the two nanotube ends, N(2) molecules oscillate along or
      parallel to the nanotube axis, and their frequencies show an inverse length
      dependence in the range of 22 to 64 GHz. Accompanying the axial oscillation, the
      molecules oscillate radially with small amplitudes in the lateral potential well.
      The corresponding frequencies have a magnitude of several hundred gigahertz, and
      the maximum exceeds 1800 GHz. These periodic oscillations contribute to the
      molecular blockage in nanotubes.

PMID- 21730587
TI  - Low-temperature electronic transport in single K(0.27)MnO(2).0.5H(2)O nanowires:
      enhanced electron-electron interaction.
AB  - The current-voltage (I-V) characteristics and electrical resistivity of isolated
      potassium manganese oxide (K(0.27)MnO(2).0.5H(2)O) nanowires prepared by a simple
      hydrothermal method were investigated over a wide temperature range from 300 to 4
      K. With lowering temperature, a transition from linear to nonlinear I-V curves
      was observed around 50 K, and a clear zero bias anomaly (i.e., Coulomb gap-like
      structure) appeared on the differential conductance (dI/dV) curves, possibly due
      to enhanced electron-electron interaction at low temperatures. The temperature
      dependence of resistivity, [Formula: see text], follows the Efros-Shklovskii (ES)
      law, as expected in the presence of a Coulomb gap. Here we note that both the ES
      law and Coulomb blockade can in principle lead to a reduced zero bias conductance
      at low temperatures; in this study we cannot exclude the possibility of Coulomb
      blockade transport in the measured nanowires, especially in the low-temperature
      range. It is still an open question how to pin down the origin of the observed
      reduction to a Coulomb gap (ES law) or Coulomb blockade.

PMID- 21730588
TI  - Hollow Ag/Pd triangular nanoplate: a novel activator for electroless nickel
      deposition.
AB  - Hollow Ag/Pd triangular nanoplates have been successfully prepared by a galvanic
      displacement reaction, in which added Pd(2+) ions react with Ag triangular
      nanoplates as templates. By altering the sizes of the Ag nanotemplates, Ag/Pd
      triangular nanoplates of different sizes can be prepared. Additionally, the large
      alloy nanoplates show maximum electrochemical activity when Ag/Pd triangular
      nanoplates of different sizes are applied as new activators for electroless
      nickel deposition.

PMID- 21730589
TI  - Poly(3,4-ethylenedioxythiophene) nanotubes as electrode materials for a high
      powered supercapacitor.
AB  - We report the fast charging/discharging capability of poly(3,4
      ethylenedioxythiophene) (PEDOT) nanotubes during the redox process and their
      potential application to a high-powered supercapacitor. PEDOT nanotubes were
      electrochemically synthesized in a porous alumina membrane, and their structures
      were characterized using electron microscopes. Cyclic voltammetry was used to
      characterize the specific capacitance of the PEDOT nanotubes at various scan
      rates. A type I supercapacitor (two symmetric electrodes) based on PEDOT nanotube
      electrodes was fabricated, and its energy density and power density were
      evaluated by galvanostatic charge/discharge cycles at various current densities.
      We show that the PEDOT-nanotube-based supercapacitor can achieve a high power
      density of 25 kW kg(-1) while maintaining 80% energy density (5.6 W h kg(-1)).
      This high power capability is attributed to the fast charge/discharge of
      nanotubular structures: hollow nanotubes allow counter-ions to readily penetrate
      into the polymer and access their internal surfaces, while the thin wall provides
      a short diffusion distance to facilitate the ion transport. Impedance
      spectroscopy shows that nanotubes have much lower diffusional resistance to
      charging ions than solid nanowires shielded by an alumina template, providing
      supporting information for the high charging/discharging efficiency of
      nanotubular structures.

PMID- 21730590
TI  - Performance of ethanol electro-oxidation on Ni-Cu alloy nanowires through
      composition modulation.
AB  - To reduce the cost of the catalyst for direct ethanol fuel cells and improve its
      catalytic activity, highly ordered Ni-Cu alloy nanowire arrays have been
      fabricated successfully by differential pulse current electro-deposition into the
      pores of a porous anodic alumina membrane (AAMs). The energy dispersion spectrum,
      scanning and transmission electron microscopy were utilized to characterize the
      composition and morphology of the Ni-Cu alloy nanowire arrays. The results reveal
      that the nanowires in the array are uniform, well isolated and parallel to each
      other. The catalytic activity of the nanowire electrode arrays for ethanol
      oxidation was tested and the binary alloy nanowire array possesses good catalytic
      activity for the electro-oxidation of ethanol. The performance of ethanol electro
      oxidation was controlled by varying the Cu content in the Ni-Cu alloy and the Ni
      Cu alloy nanowire electrode shows much better stability than the pure Ni one.

PMID- 21730591
TI  - Electrical and rheological percolation of polymer nanocomposites prepared with
      functionalized copper nanowires.
AB  - The morphological, electrical and rheological characterization of polystyrene
      nanocomposites containing copper nanowires (CuNWs) functionalized with 1
      octanethiol is presented. Characterization by SEM and TEM shows that surface
      functionalization of the nanowires resulted in significant dispersion of CuNWs in
      the PS matrix. The electrical characterization of the nanocomposites indicates
      that functionalized CuNWs start to form electrically conductive networks at lower
      concentrations (0.25 vol% Cu) than using unfunctionalized CuNWs (0.5 vol% Cu).
      The organic coating on the nanowires prevents significant changes in the
      electrical resistivity in the vicinity of the percolation threshold. Percolated
      nanocomposites showed electrical resistivity in the range of 10(6)-10(7) Omega
      cm. The transition from liquid-like to solid-like behavior (rheological
      percolation) of the nanocomposites was studied using dynamic rheology at 200 
      degrees C. Unfunctionalized CuNWs result in electrical and rheological
      percolation at similar concentrations. Functionalized CuNWs show rheological
      percolation at higher concentration (1.0-2.0 vol%) than that required for
      electrical percolation. This is attributed to the decrease in the interfacial
      tension between nanowires and polymer chains and its effect on the viscoelastic
      behavior of the combined polymer-nanowire networks.

PMID- 21730592
TI  - Real-time in situ sensing of damage evolution in advanced fiber composites using
      carbon nanotube networks.
AB  - Developments in producing nanostructured materials with novel properties have
      opened up new opportunities in which unique functionality can be added to
      existing material systems. As advanced fiber composites are utilized more
      frequently in primary structural applications there is a key challenge to enhance
      the performance and reliability while reducing maintenance. As a consequence
      there is tremendous scientific and technical interest in the development of
      techniques for monitoring the health of composite structures where real-time
      sensing can provide information on the state of microstructural damage. In this
      research we utilize electrically conductive networks of carbon nanotubes as in
      situ sensors for detecting damage accumulation during cyclic loading of advanced
      fiber composites. Here we show that, by combining load and strain measurements in
      real-time with direct current electrical resistance measurements of the carbon
      nanotube network, insight can be gained toward the evolution and accumulation of
      damage. The resistance/strain relations show substantial hysteresis due to the
      formation and opening/closing of cracks during cyclic loading. Through
      interpreting the resistance response curves we identify a parameter that may be
      utilized as a quantitative measure of damage.

PMID- 21730593
TI  - The impact of morphology upon the radiation hardness of ZnO layers.
AB  - It is shown that ZnO nanorods and nanodots grown by MOCVD exhibit enhanced
      radiation hardness against high energy heavy ion irradiation as compared to bulk
      layers. The decrease of the luminescence intensity induced by 130 MeV Xe(23+)
      irradiation at a dose of 1.5 * 10(14) cm(-2) in ZnO nanorods is nearly identical
      to that induced by a dose of 6 * 10(12) cm(-2) in bulk layers. The damage
      introduced by irradiation is shown to change the nature of electronic transitions
      responsible for luminescence. The change of excitonic luminescence to the
      luminescence related to the tailing of the density of states caused by potential
      fluctuations occurs at an irradiation dose around 1 * 10(14) cm(-2) and 5 *
      10(12) cm(-2) in nanorods and bulk layers, respectively. More than one order of
      magnitude enhancement of radiation hardness of ZnO nanorods grown by MOCVD as
      compared to bulk layers is also confirmed by the analysis of the near-bandgap
      photoluminescence band broadening and the behavior of resonant Raman scattering
      lines. The resonant Raman scattering analysis demonstrates that ZnO
      nanostructures are more radiation-hard as compared to nanostructured GaN layers.
      High energy heavy ion irradiation followed by thermal annealing is shown to be a
      way for the improvement of the quality of ZnO nanorods grown by electrodeposition
      and chemical bath deposition.

PMID- 21730594
TI  - Defect studies of ZnSe nanowires.
AB  - During the synthesis of ZnSe nanowires various point and extended defects can
      form, leading to observed stacking faults and twinning defects, and strong defect
      related emission in photoluminescence spectra. In this paper, we report on the
      development of a simple thermodynamic model for estimating the defect
      concentration in ZnSe nanowires grown under varying Se vapour pressure and for
      explaining the results of our experimental findings. Positron annihilation
      spectroscopy was used successfully for the first time for nanowires and the
      results support predictions from the defect model as well as agreeing well with
      our structural and optical characterization results. Under very high Se vapour
      pressure, Se nodules were observed to form on the sidewalls of the nanowire,
      indicating that beyond a limit, excess Se will begin to precipitate out of the
      liquid alloy droplet in the vapour-liquid-solid growth of nanowires.

PMID- 21730595
TI  - Multiwalled carbon nanotubes enhance electrochemical properties of titanium to
      determine in situ bone formation.
AB  - Multiwalled carbon nanotubes (MWCNTs) enhance osteoblast (bone-forming cell)
      calcium deposition compared to currently implanted materials (such as titanium).
      In this study, MWCNTs were grown out of nanopores anodized on titanium (MWCNT
      Ti). The electrochemical responses of MWCNT-Ti were investigated in an attempt to
      ascertain if MWCNT-Ti can serve as novel in situ sensors of bone formation. For
      this purpose, MWCNT-Ti was subjected to a ferri/ferrocyanide redox couple and its
      electrochemical behavior measured. Cyclic voltammograms (CVs) showed an enhanced
      redox potential for the MWCNT-Ti. These redox signals were superior to that
      obtained with bare unmodified Ti, which did not sense either oxidation or
      reduction peaks in the CVs. A further objective of this study was to investigate
      the redox reactions of MWCNT-Ti in a solution of extracellular components
      secreted by osteoblasts in vitro. It was found that MWCNT-Ti exhibited well
      defined and persistent CVs, similar to the ferri/ferrocyanide redox reaction. The
      higher electrodic performance and electrocatalytic activity of the MWCNT-Ti
      compared to the bare titanium observed in this study were likely due to the fact
      that MWCNTs enhanced direct electron transfer and facilitated double-layer
      effects, leading to a strong redox signal. Thus these results encourage the
      further study and modification of MWCNT-Ti to sense new bone growth in situ next
      to orthopedic implants and perhaps monitor other events (such as infection and/or
      harmful scar tissue formation) to improve the current clinical diagnosis of
      orthopedic implants.

PMID- 21730596
TI  - Enhanced x-ray irradiation-induced cancer cell damage by gold nanoparticles
      treated by a new synthesis method of polyethylene glycol modification.
AB  - We explored a very interesting gold nanoparticle system-pegylated gold in
      colloidal solution-and analyzed its uptake by mice colorectal adenocarcinoma CT26
      tumor cells and the impact on the cell's response to x-ray irradiation. We found
      that exposure to polyethylene glycol (PEG) modified ('pegylated') 4.7 +/- 2.6 nm
      gold nanoparticles synthesized by a novel synchrotron-based method enhances the
      response of CT26 cells to x-ray irradiation. Transmission electron microscopy
      (TEM) and confocal microscopy revealed that substantial amounts of such
      nanoparticles are taken up and absorbed by the cells and this conclusion is
      supported by quantitative induced coupled plasma (ICP) results. Standard tests
      indicated that the internalized particles are highly biocompatible but strongly
      enhance the cell damage induced by x-ray irradiation. Synchrotron radiation
      Fourier transform infrared (SR-FTIR) spectromicroscopy analyzed the chemical
      aspects of this phenomenon: the appearance of C = O stretching bond spectral
      features could be used as a marker for cell damage and confirmed the enhancement
      of the radiation-induced toxicity for cells.

PMID- 21730597
TI  - Two-dimensional array self-assembled quantum dot sub-diffraction waveguides with
      low loss and low crosstalk.
AB  - We model and demonstrate the behavior of two-dimensional (2D) self-assembled
      quantum dot (QD) sub-diffraction waveguides. By pumping the gain-enabled
      semiconductor nanoparticles and introducing a signal light, energy coupling of
      stimulated photons from the QDs enables light transmission along the waveguide.
      Monte Carlo simulation with randomized inter-dot separation reveals that the
      optical gain necessary for unity transfer is 3.1 * 10(7) m(-1) for a 2D (2 um
      length by 500 nm width) array compared to 11.6 * 10(7) m(-1) for a 1D (2 um
      length) given 8 nm diameter quantum dots. The theoretical results are borne out
      in experiments on 2D arrays by measurement of negligible crosstalk component with
      as little as 200 nm waveguide separation and is indicative of near-field optical
      coupling behavior. The transmission loss for 500 nm wide structures is determined
      to be close to 3 dB/4 um, whereas that for 100 nm width is 3 dB/2.3 um.
      Accordingly, higher pump power and gain would be necessary on the narrower device
      to create similar throughput. Considering existing nanoscale propagation methods,
      which commonly use negative dielectric materials, our waveguide shows an improved
      loss characteristic with comparable or smaller dimensions. Thus, the application
      of QDs to nanophotonic waveguiding represents a promising path towards ultra-high
      density photonic integrated circuits.

PMID- 21730598
TI  - The role of electrical and thermal contact resistance for Joule breakdown of
      single-wall carbon nanotubes.
AB  - Several data sets for the electrical breakdown in air of single-wall carbon
      nanotubes (SWNTs) on insulating substrates are collected and analyzed. A
      universal scaling of the Joule breakdown power with nanotube length is found,
      which appears to be independent of the substrate thermal properties of their
      thickness. This suggests that the thermal resistances at SWNT-insulator and at
      SWNT-electrode interfaces govern heat sinking from the nanotube. Analytical
      models for the breakdown power scaling are presented, providing an intuitive,
      physical understanding of the breakdown process. The electrical and thermal
      resistances at the electrode contacts limit the breakdown behavior for sub-micron
      SWNTs; the breakdown power scales linearly with length for tubes that are microns
      long, and a minimum breakdown power (~0.05 mW) is observed for the intermediate
      (~0.5 um) length range.

PMID- 21730599
TI  - Silicon nanowire-based solar cells.
AB  - The fabrication of silicon nanowire-based solar cells on silicon wafers and on
      multicrystalline silicon thin films on glass is described. The nanowires show a
      strong broadband optical absorption, which makes them an interesting candidate to
      serve as an absorber in solar cells. The operation of a solar cell is
      demonstrated with n-doped nanowires grown on a p-doped silicon wafer. From a
      partially illuminated area of 0.6 cm(2) open-circuit voltages in the range of 230
      280 mV and a short-circuit current density of 2 mA cm(-2) were obtained.

PMID- 21730600
TI  - Realization of porous poly(methyl methacrylate) films filled with
      electrodeposited carbon nanotubes.
AB  - A deposition process on a conducting surface, in which water acted as the
      dispersed phase and a mixture of poly(methyl methacrylate) and chloroform as the
      continuous phase, was applied to prepare poly(methyl methacrylate) films. The
      influence of relative humidity during the film preparation on the surface
      morphology was investigated by field emission scanning microscopy. High-humidity
      preparation conditions lead to porous poly(methyl methacrylate) films. These
      films were then used as templates to perform the selective deposition into the
      pores of single-walled carbon nanotubes by an electrophoretic method. The
      attractive properties of carbon nanotubes combined with the versatile properties
      of poly(methyl methacrylate) open up new opportunities for these nanocomposites
      to achieve novel architectures in nanodevices and microdevices.

PMID- 21730601
TI  - Gold nanocones fabricated by nanotransfer printing and their application for
      field emission.
AB  - Arrays of gold nanocones have been fabricated by the nanotransfer printing (nTP)
      method and we have utilized these nanocones for field emission. By the nature of
      the printing, any shape of metal structure can be fabricated only at desired
      locations and a step-and-repeat process, which enables large-area fabrication, is
      possible. We demonstrate step-and-repeat printing with gold nanocone patterns
      occupying an area of 9 mm * 8 mm.

PMID- 21730602
TI  - The formation mechanism of periodic Zn nanocrystal arrays embedded in an
      amorphous layer by rapid electron beam irradiation.
AB  - A periodic nano-island array of ~7 nm diameter Zn single crystals embedded in an
      amorphous Zn(2x)Si(1-x)O(2) layer was created by using rapid electron beam
      irradiation for 50 s. A sequential process of 900  degrees C thermal annealing
      followed by electron beam irradiation induces the formation of an amorphous
      Zn(2x)Si(1-x)O(2) layer containing periodic Zn nanocrystals. It is shown that the
      periodic Zn crystal array can be produced with good control of their size and
      spacing. Possible formation mechanisms for the Zn crystal nano-islands are
      described on the basis of the experimental results.

PMID- 21730603
TI  - Dye-sensitized nickel(II)oxide photocathodes for tandem solar cell applications.
AB  - To date, nickel(II) oxide (NiO) is one of the few p-type semiconductors that has
      successfully been used for the construction of dye-sensitized photocathodes as
      well as tandem dye-sensitized solar cells. In this study we present a novel
      fabrication method for the preparation of mesoporous NiO films based on preformed
      NiO nanopowders. Critical properties such as pore-size distribution,
      crystallinity, and internal surface area of the resulting NiO films were
      controlled through the sintering process and optimized for their application as
      dye-sensitized photocathodes, resulting in a significantly increased photovoltaic
      performance, compared to earlier studies. A series of different sensitizers and
      electrolytes was scrutinized for their application in dye-sensitized NiO
      photocathodes. Despite its limited absorption range the dye coumarin 343 clearly
      outperforms other sensitizers used in this study. Values for short-circuit
      current densities of 2.13 mA cm(-2) and overall energy conversion efficiencies of
      0.033% under simulated sunlight (AM1.5, 1000 W m(-2)) are the highest values
      reported in literature so far.

PMID- 21730604
TI  - Surfactant assisted synthesis and spectroscopic characterization of selenium
      nanoparticles in ambient conditions.
AB  - In this work, an attempt has been made to synthesize well-distributed stable
      selenium (Se) particles of nanosize dimensions via an aqueous micellar solution
      by the assistance of surfactants of two different polarities (anionic, sodium
      bis(2-ethylhexyl)sulfosuccinate (AOT) and cationic, hexadecyltrimethylammonium
      bromide (CTAB)). The morphology of the particles was examined with transmission
      electron microscopy (TEM). X-ray analysis reveals that the particles have a
      monoclinic structure. The band gap of the particles was determined from UV
      visible optical spectroscopic results. The size variation was estimated by
      employing a quantum confinement effect equation. The evolution of the selenium
      nanoparticles in AOT and CTAB micellar media was corroborated with the time
      dependent absorption spectra. The influence of hydrazine hydrate concentrations
      on the formation kinetics of Se nanoparticles was also investigated. The capping
      ability of the surfactants has been quantitatively evaluated from Fourier
      transform infrared (FTIR) studies.

PMID- 21730605
TI  - Growth of carbon nanofibers on carbon fabric with Ni nanocatalyst prepared using
      pulse electrodeposition.
AB  - The pulse electrodeposition (PED) technique was utilized to deposit nanosized
      (<=10 nm) Ni catalysts on carbon fabric (CF). Via an in situ potential profile,
      the PED technique can control the Ni catalyst loading, which is an important
      parameter for the growth of carbon nanofibers (CNFs) on CF. The preparation of
      CNF-coated CF (carpet-like CF) was carried out in a thermal chemical vapor
      deposition system with an optimum loading of Ni catalysts deposited in the PED
      pulse range from 20 to 320 cycles. CNFs grown at 813 K using different pulse
      cycles had a narrow diameter distribution, around 15 +/- 5 nm to 29 +/- 7 nm;
      they have a hydrophobic surface, like lotus leaves. Transmission electron
      microscopy images confirmed the graphene structural transformation of CNFs with
      the growth temperature. Solid wire CNFs were initially grown at 813 K with
      graphene edges exposed on the external surface. At elevated growth temperatures
      (1073 and 1173 K), bamboo-like CNFs were obtained, with herringbone structures
      and intersectional hollow cores.

PMID- 21730606
TI  - Reconciliation between experimental and Monte Carlo-based simulation of the pore
      size distribution in mesoporous silicon.
AB  - It is demonstrated for the first time that mesoporous PS structures obtained by
      the electrochemical etching of p(+)(100) oriented silicon wafers might assume the
      peculiarity of invariance of the first peak positions in their pore size
      distribution curves, albeit for current densities far from the electropolishing
      region and at constant electrolyte composition. A new Monte Carlo-based
      simulation model is presented that predicts reasonably the pore size distribution
      of the PS layers and the observed invariance of peak position with respect to
      changes in current density. The main highlight of the new model is the
      introduction of a 'light avalanche breakdown' process in a mathematical fashion.
      The model is also able to predict an absolute value of 4.23 A for the smallest
      pore created experimentally. It is discussed that the latter value has an exact
      physical meaning: it corresponds with great accuracy to the width of a void
      created on the surface due to the exclusion of one Si atom.

PMID- 21730607
TI  - Functionalization of atomic force microscope tips by dielectrophoretic assembly
      of Gd(2)O(3):Eu(3+) nanorods.
AB  - An atomic force microscopy (AFM) tip has been coated with photoluminescent Eu(3+)
      doped Gd(2)O(3) nanorods using a dielectrophoresis technique, which preserves the
      red emission of the nanorods (quantum yield 0.47). The performance of the
      modified tips has been tested by using them for regular topography imaging in
      tapping and contact modes. Both a regular AFM standard grid and a patterned
      surface (of an organic-inorganic methacrylate Zr-based oxo-cluster and
      poly(oxyethylene)/siloxane hybrid) have been used. Similar depth values have been
      measured using a conventional silicon tip and the nanorod-modified tip. The tips
      before and after use exhibit similar SEM images and photoluminescence spectra
      and, thus, seem to be stable under working conditions. These tips should find
      applications in scanning near-field optical microscopy and other scanning
      techniques.

PMID- 21730608
TI  - Growth of Ag nanometre-sized particles in solution: molecular dynamics
      simulations.
AB  - This work focuses on the growth of nanometre-sized Ag clusters in solution.
      Molecular dynamics simulations have been employed to gain the necessary detail on
      the dynamics of solute species and to study the mechanistic features of the
      processes governing the association of solute atoms in aggregates. Supersaturated
      liquid solutions of Ag in tetrachloromethane have been considered. A systematic
      variation of the concentration of Ag atoms in solution permitted us to show the
      different mechanistic scenarios responsible for the growth processes of solid Ag
      clusters. It is shown that such processes are limited by the thermal diffusion of
      solute in the solution bulk at relatively low supersaturation degrees, whereas
      the growth is limited by interfacial effects at relatively high supersaturation
      degrees.

PMID- 21730609
TI  - Time-resolved photoluminescence of type-II Ga(As)Sb/GaAs quantum dots embedded in
      an InGaAs quantum well.
AB  - Optical properties and carrier dynamics in type-II Ga(As)Sb/GaAs quantum dots
      (QDs) embedded in an InGaAs quantum well (QW) are reported. A large blueshift of
      the photoluminescence (PL) peak is observed with increased excitation densities.
      This blueshift is due to the Coulomb interaction between physically separated
      electrons and holes characteristic of the type-II band alignment, along with a
      band-filling effect of electrons in the QW. Low-temperature (4 K) time-resolved
      PL measurements show a decay time of [Formula: see text] ns from the transition
      between Ga(As)Sb QDs and InGaAs QW which is longer than that of the transition
      between Ga(As)Sb QDs and GaAs two-dimensional electron gas ([Formula: see text]
      ns).

PMID- 21730610
TI  - Strong blue photoluminescence from single-crystalline bismuth oxychloride
      nanoplates.
AB  - Single-crystalline bismuth oxychloride (BiOCl) nanoplates with in-plane sizes of
      200-500 nm and a thickness of 15-25 nm are synthesized by a simple solution
      route. Strong blue photoluminescence centred at 455 nm (~2.72 eV) with very high
      quantum yields (Phi(PL)~0.4) has been observed at room temperature, representing
      the first report of strong room temperature photoluminescence from bismuth
      oxyhalide nanomaterials. It is envisaged that bismuth oxychloride could join the
      family of non-cadmium based high-efficiency emitters; it has promising
      applications in various fields, especially in light emitting diodes, lasers and
      solar cells.

PMID- 21730611
TI  - Field emission from zinc oxide nanotowers: the role of the top morphology.
AB  - Arrays of novel nanometer-scale tower-shaped structures of zinc oxide (ZnO
      nanotowers) were synthesized by a simple thermal evaporation method. Due to the
      difference in fabrication conditions, ZnO nanotowers with similar body structure
      but different top morphologies were obtained. These ZnO nanotowers with different
      top morphologies showed obvious disparity in field emission, despite their
      overall field enhancement factor and density being the same. The nanotowers with
      the sharpest top had the lowest turn-on and threshold electric field. This
      disparity is attributed to the different local field enhancement factors at the
      nanotower tops, which were calculated both from the field emission data and by
      simulation. The above results have demonstrated the essential importance of the
      top morphology of a ZnO nanostructure in field emission.

PMID- 21730612
TI  - Site-selective spectroscopy in Sm(3+)-doped sol-gel-derived nano-glass-ceramics
      containing SnO(2) quantum dots.
AB  - Nano-glass-ceramics of composition 95SiO(2)-5SnO(2) doped with 0.4 Sm(3+) (mol%)
      were synthesized by the thermal treatment of precursor sol-gel glasses.
      Structural and luminescence measurements were carried out. The precipitated
      SnO(2) nanocrystals in the glass matrix constitute a wide bandgap quantum-dot
      system with size comparable to the bulk exciton Bohr radius. A site-selective
      excitation, by energy transfer from the semiconductor host, reveals that a
      fraction of the Sm(3+) ions are incorporated in the SnO(2) nanocrystals, whereas
      the rest remains in the silica glassy phase. An evolution in the Sm(3+) emission
      spectra has been observed when the SnO(2) nanocrystals are excited with different
      UV wavelengths, which has been ascribed to selective excitation of nanocrystal
      sets with predetermined size.

PMID- 21730613
TI  - Nanomechanical properties of a Ni nanodot-patterned surface.
AB  - Nanomechanical properties of a Ni nanodot-patterned surface (NDPS) on a Si
      substrate were investigated using nanoindentation. The Ni NDPS was fabricated by
      thermal evaporation of Ni through a porous anodized aluminum oxide template onto
      a Si substrate. Plan-view transmission electron microscopy and nanobeam
      diffraction were used to characterize the Ni nanodot crystal structure. Scanning
      electron microscopy and atomic force microscopy were used to characterize the
      morphology and deformation of the Ni nanodots before and after nanoindentation.
      The elastic modulus and hardness of the Ni nanodots were found to be 159 +/- 22
      and 7.7 +/- 1.0 GPa, respectively. The critical shear stress for initiating
      plastic deformation in the Ni nanodot was estimated to be 8.3 +/- 1.0 GPa, which
      is close to the theoretical shear strength of 7.6 GPa in dislocation-free single
      crystal Ni.

PMID- 21730614
TI  - Recent progress in carbon nanotube-based gas sensors.
AB  - The development of carbon nanotube-(CNTs-)based gas sensors and sensor arrays has
      attracted intensive research interest in the last several years because of their
      potential for the selective and rapid detection of various gaseous species by
      novel nanostructures integrated in miniature and low-power consuming electronics.
      Chemiresistors and chemical field effect transistors are probably the most
      promising types of gas nanosensors. In these sensors, the electrical properties
      of nanostructures are dramatically changed when exposed to the target gas
      analytes. In this review, recent progress on the development of different types
      of CNT-based nanosensors is summarized. The focus was placed on the means used by
      various researchers to improve the sensing performance (sensitivity, selectivity
      and response time) through the rational functionalization of CNTs with different
      methods (covalent and non-covalent) and with different materials (polymers and
      metals).

PMID- 21730615
TI  - Surface nanocrystallization of stainless steel for reduced biofilm adherence.
AB  - Stainless steel is one of the most common metallic biomedical materials. For
      medical applications, its resistance to the adherence of biofilms is of
      importance to the elimination or minimization of bacterial infections. In this
      study, we demonstrate the effectiveness of a process combining surface
      nanocrystallization and thermal oxidation (or a recovery heat treatment in air)
      for reducing the biofilm's adherence to stainless steel. During this treatment, a
      target surface was sandblasted and the resultant dislocation cells in the surface
      layer were turned into nanosized grains by a subsequent recovery treatment in
      air. This process generated a more protective oxide film that blocked the
      electron exchange or reduced the surface activity more effectively. As a result,
      the biofilm's adherence to the treated surface was markedly minimized. A
      synthetic peptide was utilized as a substitute of biofilms to evaluate the
      adhesion between a treated steel surface and biofilms using an atomic force
      microscope (AFM) through measuring the adhesive force between the target surface
      and a peptide-coated AFM tip. It was shown that the adhesive force decreased with
      a decrease in the grain size of the steel. The corresponding surface electron
      work function (EWF) of the steel was also measured, which showed a trend of
      variation in EWF with the grain size, consistent with corresponding changes in
      the adhesive force.

PMID- 21730616
TI  - Gate-controlled rectifying barrier in a two-dimensional hole gas.
AB  - The current flowing in a homogeneous low-dimensional conductor is shown to be
      rectified by a gate-controlled asymmetric barrier resembling a Schottky barrier.
      The barrier shape is set by varying the potential along a nanofabricated
      nonequipotential gate which allows simple external control over the device
      function independent of material properties. A forward-to-reverse current ratio
      of more than 10(4) is obtained. The merits of diodes fabricated in this way with
      respect to conventional diodes are discussed.

PMID- 21730617
TI  - Charge contrast imaging of suspended nanotubes by scanning electron microscopy.
AB  - A method of rapidly identifying and imaging suspended nanotubes by scanning
      electron microscopy is reported. Nanotubes are visible in high contrast and even
      at low magnification. The contrast can be explained by considering the effect
      that the charge on the nanotube has on the substrate. The proposed mechanism is
      general and should apply to any charged nanostructure in proximity to a surface
      or interface. This represents a new contrast mechanism in scanning electron
      microscopy.

PMID- 21730618
TI  - Tuning shades of white light with multi-color quantum-dot-quantum-well emitters
      based on onion-like CdSe-ZnS heteronanocrystals.
AB  - We present white light generation controlled and tuned by multi-color quantum-dot
      quantum-well emitters made of onion-like CdSe/ZnS/CdSe core/shell/shell
      heteronanocrystals integrated on InGaN/GaN light-emitting diodes (LEDs). We
      demonstrate hybrid white LEDs with (x, y) tristimulus coordinates tuned from
      (0.26, 0.33) to (0.37, 0.36) and correlated color temperatures from 27 413 to
      4192 K by controlling the number of their integrated red-green-emitting
      heteronanocrystals. We investigate the modification of in-film emission from
      these multi-layered heteronanocrystals with respect to their in-solution
      emission, which plays a significant role in hybrid LED applications. Our proof-of
      principle experiments indicate that these complex heteronanocrystals hold promise
      for use as nanoluminophors in future hybrid white LEDs.

PMID- 21730619
TI  - The effect of adsorbates on the space-charge-limited current in single ZnO
      nanowires.
AB  - We studied the influence of adsorbates on the space-charge-limited current (SCLC)
      in individual ZnO nanowires through varying the bias voltage, laser illumination,
      and ambient pressure. In dark and air conditions, the free carriers were depleted
      by the surface adsorbates, and electrons injected from the electrode to the
      nanowire dominated the electron transport properties. Under laser illumination,
      the current-voltage characteristic was linear at low voltage and superlinear at
      high voltage, and the SCLC regime occurred at high voltages due to the surface
      desorption. The time response of photoconductivity further revealed the dynamic
      process of elimination of SCLC by desorption of oxygen molecules at the ZnO
      nanowire surface.

PMID- 21730620
TI  - Patterning photo-curable light-emitting organic composites by vertical and
      horizontal capillarity: a general route to photonic nanostructures.
AB  - We demonstrate the patterning of organic light-emitting composites made by
      conjugated polymers and photo-curable matrices. Using blends that exhibit both
      the structural properties of a low-viscosity photo-curable polymer, and the
      emission features of conjugated light-emitting materials, we study the
      operational principle of the pattern transfer and the modifications induced by
      the imprinting and microfluidic procedures on the optical properties of the
      compounds investigated. The combination of high-resolution silicone and
      perfluoropolyether elastomeric templates and low-viscosity, light-emitting
      polymeric blends offers the possibility to easily produce active organic
      structures with 100 nm scale resolution, thus extending current nanopatterning
      routes to this important class of composite material.

PMID- 21730621
TI  - Single-crystalline Bi(2)S(3) nanowire network film and its optical switches.
AB  - A single-crystalline bismuth sulfide (Bi(2)S(3)) nanowire network film at a
      centimeter scale is fabricated by the facile hydrothermal method. The Bi(2)S(3)
      film is easily tape-transferred onto a soft plastic substrate, and is further
      used to fabricate optical switches by screen-printing an Ag electrode array on
      its top. Our studies demonstrate that the Bi(2)S(3) nanowire network has a
      pronounced increase in conductance upon exposure to visible light, and possesses
      a very fast response time of about 2 ms. This work provides a simple and economic
      method to fabricate a high performance optical switch array and could offer great
      potential for a low cost, mass-manufacturing process.

PMID- 21730622
TI  - Nanopatterned monolayers of an adsorbed chromophore.
AB  - A simple lift-off process was developed to rapidly fabricate nanopatterned
      photofunctional surfaces. Dye molecules of a perylene derivative (PDID) were
      adsorbed irreversibly on clean silicon through the holes of an electron-beam
      lithographied polymer mask. The subsequent removal of the mask in a proper
      solvent results in PDID nanosized regions of width as small as 30 nm for stripes
      and of diameter as small as 120 nm for dots. Numerical analyses of atomic force
      microscopy and laser-scanning confocal microscopy images show that the dye
      molecules are confined to the regions defined by the lithographic process, with
      the integrated fluorescence intensity being essentially proportional to the size
      of the nanofeatures. This demonstrates that a simple organic lift-off process
      compatible with clean-room technology, and not involving any chemical step, is
      able to produce photofunctional nanopatterned surfaces, even though the dye is
      not chemically bonded to the silicon surface.

PMID- 21730623
TI  - Effects of pulse voltage on inkjet printing of a silver nanopowder suspension.
AB  - Inkjet printing of a liquid suspension prepared by dispersing silver powders of
      size around 4 nm in deionized (DI) water at 30 wt% was investigated in this
      study. By comparing with the results of pure DI water, the effects of
      nanoparticles on droplet formation between the nozzle and the substrate were also
      studied. A bipolar pulse waveform was employed in driving the piezoelectric
      printhead with pulse voltage set as the primary variable of this study.
      Observations showed that a higher driving pulse voltage was required for the
      silver suspension to form droplets than DI water. The liquid column broke up at
      the nozzle orifice for DI water while the silver suspension broke up further away
      below the nozzle office. It was also observed that the droplet size of the silver
      suspension was smaller than that of DI water. For the silver suspension the
      liquid column formed was thinner and longer and the pinch-off time of the liquid
      column to form droplets was also longer. However, the characteristic adjustment
      time for droplet recombination was shorter for the silver suspension than for DI
      water.

PMID- 21730624
TI  - Tuning the morphologies of SiC nanowires via the control of growth temperature,
      and their photoluminescence properties.
AB  - Single crystalline SiC nanowires were synthesized by a catalyst free vapor
      deposition method using elemental silicon and graphite carbon as the starting
      materials. The phase, morphology, crystal structure, and defects of the products
      were characterized by x-ray diffraction, field emission scanning electron
      microscopy, and transmission electron microscopy. Within a 6 h reaction time, the
      morphology of the SiC nanowires can be tuned to cylinder, hexagonal prism, or
      bamboo shape by simply altering the reaction temperature from 1470  degrees C,
      1550  degrees C to 1630  degrees C, respectively. The photoluminescence of these
      differently shaped SiC nanowires was measured and is discussed. Based on the
      characterization results, the vapor-solid growth mechanisms for the multi-shaped
      SiC nanowires are proposed by taking into account the possible reactions between
      intermediate gas phases, the reaction steps, and the surface energy minimization.

PMID- 21730625
TI  - Growth of one-dimensional Si/SiGe heterostructures by thermal CVD.
AB  - The first results on a simple new process for the direct fabrication of one
      dimensional superlattices using common CVD chambers are presented. The
      experiments were carried out in a 200 mm industrial Centura reactor (Applied
      Materials). Low dimensionality and superlattices allow a significant increase in
      the figure of merit of thermoelectrics by controlling the transport of phonons
      and electrons. The monocrystalline nanowires produced according to this process
      are both one-dimensional and present heterostructures, with very thin layers (40
      nm) of Si and SiGe. Concentrations up to 30 at.% Ge were obtained in the SiGe
      parts. Complementary techniques including transmission electronic microscopy
      (TEM), selected area electron diffraction (SAED), energy dispersive x-ray
      spectroscopy (EDS), scanning transmission electron microscopy (STEM) in bright
      field and high angle annular dark field (HAADF STEM), and energy-filtered
      transmission electron microscopy (EF-TEM) were used to characterize the
      nanoheterostructures.

PMID- 21730626
TI  - Fabrication and characterization of a flow-through nanoporous gold nanowire/AAO
      composite membrane.
AB  - The fabrication of a composite membrane of nanoporous gold nanowires and anodic
      aluminum oxide (AAO) is demonstrated by the electrodeposition of Au-Ag alloy
      nanowires into an AAO membrane, followed by selective etching of silver from the
      alloy nanowires. This composite membrane is advantageous for flow-through type
      catalytic reactions. The morphology evolution of the nanoporous gold nanowires as
      a function of the diameter of the Au-Ag nanowire 'precursors' is also
      investigated.

PMID- 21730627
TI  - Spark plasma sintered Sm(2)Co(17)-FeCo nanocomposite permanent magnets
      synthesized by high energy ball milling.
AB  - Nanocomposite Sm(2)Co(17)-5 wt% FeCo magnets were synthesized by high energy ball
      milling followed by consolidation into bulk shape by the spark plasma sintering
      technique. The evolution of magnetic properties was systematically investigated
      in milled powders as well as in spark plasma sintered samples. A high energy
      product of 10.2 MGOe and the other magnetic properties of M(s) = 107 emu g(-1),
      M(r) = 59 emu g(-1), M(r)/M(s) = 0.55 and H(c) = 6.4 kOe were achieved in a 5 h
      milled and spark plasma sintered Sm(2)Co(17)-5 wt% FeCo nanocomposite magnet. The
      spark plasma sintering was carried out at 700  degrees C for 5 min with a
      pressure of 70 MPa. The nanocomposite showed a higher Curie temperature of 955 
      degrees C for the Sm(2)Co(17) phase in comparison to its bulk Curie temperature
      for the Sm(2)Co(17) phase (920  degrees C). This higher Curie temperature can
      improve the performance of the magnet at higher temperatures.

PMID- 21730628
TI  - The effect of pre-treatment methods on morphology and size distribution of multi
      walled carbon nanotubes.
AB  - Multi-walled carbon nanotubes (MWCNTs) are important materials with a unique
      combination of mechanical, electrical and thermal properties. MWCNTs usually
      exist as tangled aggregates embedding impurities such as catalysts or amorphous
      carbon. Therefore, purification and cutting process are essential processes to
      get the well-dispersed solutions in solvents or a polymer matrix for diverse
      practical applications. In this study, we used MWCNTs with high purity (>95%) and
      focused on the cutting effects on the size distribution of MWCNTs. Their size
      distribution after the cutting process is expected to be a very important factor
      in determining the final properties of the polymer-MWCNT composite. Gel
      permeation chromatography (GPC) was effectively demonstrated in analyzing the
      effect of treatment methods on a size distribution of pre-treated MWCNTs in
      organic solvent. MWCNT was treated by two different methods. One is an oxidation
      process with H(2)SO(4)/HNO(3) solution and the other is an ultrasonic process
      with high power. MWCNTs were shortened simply by applying high power
      ultrasonication with narrow length distribution. Meanwhile, the acid-treated
      MWCNTs became much broader in their sizes and more flexible in their rigidities.
      These differences led to a different behavior in electric conductivity. These
      studies promise to optimize pre-treatment processes for tailoring suitable MWCNTs
      towards future applications.

PMID- 21730629
TI  - Carbon saturation of arrays of Ni catalyst nanoparticles of different size and
      pattern uniformity on a silicon substrate.
AB  - The kinetics of saturation of Ni catalyst nanoparticle patterns of the three
      different degrees of order, used as a model for the growth of carbon nanotips on
      Si, is investigated numerically using a complex model that involves surface
      diffusion and ion motion equations. It is revealed that Ni catalyst patterns of
      different degrees of order, with Ni nanoparticle sizes up to 12.5 nm, exhibit
      different kinetics of saturation with carbon on the Si surface. It is shown that
      in the cases examined (surface coverage in the range of 1-50%, highly disordered
      Ni patterns) the relative pattern saturation factor calculated as the ratio of
      average incubation times for the processes conducted in the neutral and ionized
      gas environments reaches 14 and 3.4 for Ni nanoparticles of 2.5 and 12.5 nm,
      respectively. In the highly ordered Ni patterns, the relative pattern saturation
      factor reaches 3 for nanoparticles of 2.5 nm and 2.1 for nanoparticles of 12.5
      nm. Thus, more simultaneous saturation of Ni catalyst nanoparticles of sizes in
      the range up to 12.5 nm, deposited on the Si substrate, can be achieved in the
      low-temperature plasma environment than with the neutral gas-based process.

PMID- 21730630
TI  - Tuning the dispersion of multiwall carbon nanotubes in co-continuous polymer
      blends: a generic approach.
AB  - Melt-mixed blends of polyamide 6 and acrylonitrile-butadiene-styrene (PA6/ABS)
      with multiwall carbon nanotubes (MWNTs) were prepared with the intention to
      develop conducting composites. A generic strategy, namely specific interactions
      combined with reactive coupling, was adopted to facilitate and to retain the
      'network-like' structure of MWNTs during melt-mixing. This was facilitated by the
      sodium salt of 6-amino hexanoic acid (Na-AHA) and certain phosphonium based
      modifiers, where it was envisaged that these modifiers would establish specific
      interactions (either 'cation-pi' or 'pi-pi' ) with the 'pi-electron' clouds of
      MWNTs, as well as restricting them in the PA6 phase of the blends via reactive
      coupling. This route eventually led to a remarkable increase in the electrical
      conductivity and dielectric constant in the blends with MWNTs. Raman, FTIR and
      TEM investigations further supported these observations.

PMID- 21730631
TI  - Nanocrystallized SrHA/SrHA-SrTiO(3)/SrTiO(3)-TiO(2) multilayer coatings formed by
      micro-arc oxidation for photocatalytic application.
AB  - Novel photocatalytic coatings containing strontium hydroxyapatite (SrHA),
      strontium titanate (SrTiO(3)), and TiO(2) were formed by micro-arc oxidation
      (MAO) in an aqueous electrolyte containing strontium acetate and beta
      glycerophosphate disodium at 530 V for 0.1-5 min. The structure evolution of the
      coatings was investigated as a function of processing time, and the
      photocatalytic activity of the coatings was evaluated by measuring the
      decomposition rate of methyl orange under ultraviolet irradiation. During the MAO
      processing of the coatings, it was observed that some granules appeared in the
      electrolyte adjacent to the anode and they increased in amount as the processing
      time was prolonged. The obtained results show that the granules are amorphous and
      poorly crystallized SrHA with negative charges. The coating prepared for 5 min
      presents a microporous structure of SrHA/SrHA-SrTiO(3)/SrTiO(3)-TiO(2)
      multilayers, in which the SrHA outermost layer and the SrHA-SrTiO(3) intermediate
      layer are nanocrystallized. It is suggested that formation of the granules,
      electro-migration of the granules onto the pre-formed layer, and crystallization
      of the adhered granules are possible mechanisms for the formation of a SrHA/SrHA
      SrTiO(3)/SrTiO(3)-TiO(2) multilayer coating. This coating shows much higher
      photocatalytic decomposition efficiency relative to the MAO-formed TiO(2)
      coating, and is expected to have an important photocatalytic application.

PMID- 21730632
TI  - On the electronic and geometric structures of armchair GeC nanotubes: a hybrid
      density functional study.
AB  - Ab initio calculations within the framework of hybrid density functional theory
      and the finite cluster approximation have been performed for the electronic and
      geometric structures of three different types of armchair germanium carbide
      nanotube, from (3, 3) to (11, 11). Full geometry and spin optimizations with
      unrestricted symmetry have been performed. Physically pertinent quantities of
      interest such as the cohesive energies, band gaps, radial buckling, density of
      states, dipole moments, and Mulliken charge distributions have been investigated
      in detail for all nanotubes. For type I nanotubes, the largest cohesive energy
      obtained is 4.092 eV/atom, whereas for type II and type III nanotubes, the values
      are 3.987 eV/atom and 3.968 eV/atom, respectively. For optimized type I
      nanotubes, Ge atoms moved toward the tube axis and C atoms moved in the opposite
      direction after relaxation, opposite to the trends observed in types II and III.
      The band gaps for type I nanotubes are larger than the bulk 3C-GeC gap, varying
      between 2.666 and 3.016 eV, while type II and type III nanotubes have
      significantly lower band gaps, with all nanotubes being semiconducting in nature.
      Mulliken charge analysis indicates primarily ionic behavior for type I GeC
      nanotubes and a mixed ionic with covalent behavior for the other two types. None
      of the tubes appear to be magnetic. Applications in the field of nano
      optoelectronic devices, molecular electronics, and band gap engineering are
      envisioned for GeC nanotubes.

PMID- 21730633
TI  - Functionalizing graphene by embedded boron clusters.
AB  - We present a model system that might serve as a blueprint for the controlled
      layout of graphene based nanodevices. The systems consists of chains of B(7)
      clusters implanted in a graphene matrix, where the boron clusters are not
      directly connected. We show that the graphene matrix easily accepts these
      alternating B(7)-C(6) chains and that the implanted boron components may
      dramatically modify the electronic properties of graphene based nanomaterials.
      This suggests a functionalization of graphene nanomaterials, where the
      semiconducting properties might be supplemented by parts of the graphene matrix
      itself, but the basic wiring will be provided by alternating chains of implanted
      boron clusters that connect these areas.

PMID- 21730634
TI  - The morphology and texture of Cu nanorod films grown by controlling the
      directional flux in physical vapor deposition.
AB  - We report the creation of unusual biaxial textures in Cu nanorod films, through
      the control of the incident vapor flux during oblique angle deposition. High
      density twin boundaries were formed using a periodic azimuthal swing rotation of
      the substrate while the incident angle of the Cu flux was fixed at 85 degrees 
      with respect to the surface normal. In contrast, depositions on stationary
      substrates resulted in nanorod films with a much lower density of twinned
      crystals. From transmission electron microscopy and x-ray pole figure analysis,
      the nanorod axis was shown to coincide approximately with the [Formula: see text]
      crystallographic directions. We also observed the branching of these
      nanostructures into 'nanotrees'. This branching was attributed to the creation of
      edge dislocations during the deposition and was particularly prevalent for the
      case of swing rotation. The mechanisms for the development of texture, twinning,
      and branching in these nanostructures are discussed.

PMID- 21730635
TI  - Effects of nano-surface properties on initial osteoblast adhesion and Ca/P
      adsorption ability for titanium alloys.
AB  - Titanium alloys (Ti6Al4V), while subjected to high temperature surface treatment,
      experience altered nano-surface characteristics. The effects of such surface
      treatments are examined, including the initial adhesion force experienced by
      osteoblasts, the Ca/P adsorption capability, and the nano-surface properties,
      including the amounts of amphoteric Ti-OH groups, surface topography, and surface
      roughness. The initial adhesion force is considered a quantitative indicator of
      cyto-compatibility in vitro. Previously, a cyto-detacher was applied in a pioneer
      attempt measuring the initial adhesion force of fibroblasts on a metal surface.
      Presently, the cyto-detacher is further applied to evaluate the initial adhesion
      force of osteoblasts. Results reveal that (1) titanium alloys subjected to heat
      treatment could promote the adsorption capability of Ca and P; (2) titanium
      alloys subjected to heat treatment could have higher initial osteoblast adhesion
      forces; (3) the adhesion strength of osteoblasts, ranging from 38.5 to 58.9 nN
      (nanonewtons), appears stronger for rougher surfaces. It is concluded that the
      heat treatment could have impacted the biocompatibility in terms of the initial
      osteoblast adhesion force and Ca/P adsorption capability.

PMID- 21730636
TI  - Reliable lateral and vertical manipulations of a single Cu adatom on a Cu(111)
      surface with multi-atom apex tip: semiempirical and first-principles simulations.
AB  - We study the reliability of the lateral manipulation of a single Cu adatom on a
      Cu(111) surface with single-atom, dimer and trimer apex tips using both
      semiempirical and first-principles simulations. The dependence of the
      manipulation reliability on tip height is investigated. For the single-atom apex
      tip the manipulation reliability increases monotonically with decreasing tip
      height. For the dimer and trimer apex tips the manipulation reliability is
      greatly improved compared to that for the single-atom apex tip over a certain tip
      height range. Two kinds of mechanism are found responsible for this improvement.
      One is the so-called enhanced interaction mechanism in which the lateral tip
      adatom interaction in the manipulation direction is improved. The other is the
      suspended atom mechanism in which the relative lateral trapping ability of the
      tip is improved due to the strong vertical attraction of the tip on the adatom.
      Both mechanisms occur in the manipulations with the trimer apex tip, while in
      those with the dimer apex tip only the former is effective. Moreover, we present
      a method to realize reversible vertical manipulation of a single atom on a
      Cu(111) surface with the trimer apex tip, based on its strong vertical and
      lateral attraction on the adatom.

PMID- 21730637
TI  - Mechanical and electrical properties of stretched clean and H-contaminated Pd
      nanowires.
AB  - We analyze theoretically the formation of stretched Pd-nanowires and their
      interaction with hydrogen. In our approach, we simulate the nanowire stretching
      process using a first-principles molecular-dynamics method to obtain realistic
      atomic geometries of the contact in its final stages before the nanowire breaks.
      The electrical conductance of the nanowire is also calculated at each point of
      the deformation path. For the clean Pd-nanowire in the last stages of the
      deformation process we find that the nanowire develops, first, a one-atom-neck
      and, at the end, a dimer whose bond is finally broken. For these atomic
      configurations, the calculated electrical conductances are in good agreement with
      the experimental evidence. The interaction with hydrogen is analyzed adsorbing
      one or two H atoms on the Pd-nanowire for different configurations along the
      stretching process. In the case of one H atom we obtain geometries with
      conductances in the range 0.8-1.4G(0), while for two H atoms we find conductance
      plateaus with values ~0.5G(0) and ~1.0G(0). These results are in excellent
      agreement with the experimental evidence for nanocontact breaking in an H(2)
      atmosphere and indicate that the conductance peak around 0.5G(0) observed
      experimentally is associated with nanowires where two H atoms have been adsorbed.

PMID- 21730638
TI  - Axonal guidance on patterned free-standing nanowire surfaces.
AB  - We demonstrate high-fidelity guidance of axons using rows of nanowires. The axons
      are prevented from crossing the rows, making it possible to guide and sort a
      large number of axons as opposed to when chemical patterns are used. Focal
      adhesion forms at the nanowires establishing a possible site of information
      transfer between the surface and the cells. Rows of gallium phosphide (GaP)
      nanowires were epitaxially grown on GaP(111) substrates in patterns defined by
      electron beam lithography.

PMID- 21730639
TI  - Localized surface plasmon-induced emission enhancement of a green light-emitting
      diode.
AB  - The output enhancement of a green InGaN/GaN quantum-well (QW) light-emitting
      diode (LED) through the coupling of a QW with localized surface plasmons (LSPs),
      which are generated on Ag nanostructures on the top of the device, is
      demonstrated. The suitable Ag nanostructures for generating LSPs of resonance
      energies around the LED wavelength are formed by controlling the Ag deposition
      thickness and the post-thermal-annealing condition. With a 20 mA current injected
      onto the LED, enhancements of up to 150% in electroluminescence peak intensity
      and of 120% in integrated intensity are observed. By comparing this with a
      similar result for a blue LED previously published, it is confirmed that surface
      plasmon coupling for emission enhancement can be more effective for an InGaN/GaN
      QW of lower crystal quality, which normally corresponds to the emission of a
      longer wavelength.

PMID- 21730640
TI  - A reliable method for the counting and control of single ions for single-dopant
      controlled devices.
AB  - By 2016, transistor device size will be just 10 nm. However, a transistor that is
      doped at a typical concentration of 10(18) atoms cm(-3) has only one dopant atom
      in the active channel region. Therefore, it can be predicted that conventional
      doping methods such as ion implantation and thermal diffusion will not be
      available ten years from now. We have been developing a single-ion implantation
      (SII) method that enables us to implant dopant ions one-by-one into
      semiconductors until the desired number is reached. Here we report a simple but
      reliable method to control the number of single-dopant atoms by detecting the
      change in drain current induced by single-ion implantation. The drain current
      decreases in a stepwise fashion as a result of the clusters of displaced Si atoms
      created by every single-ion incidence. This result indicates that the single-ion
      detection method we have developed is capable of detecting single-ion incidence
      with 100% efficiency. Our method potentially could pave the way to future single
      atom devices, including a solid-state quantum computer.

PMID- 21730641
TI  - Low-resistance ohmic contacts to SiC nanowires and their applications to field
      effect transistors.
AB  - We report on the electrical characterization of two ohmic contacts (Ti/Au and
      Ni/Au) to unintentionally doped silicon carbide nanowires (SiCNWs) using the
      modified transmission line model (TLM) method. Our results indicate that
      subsequently deposited Ni/Au ohmic contacts on SiCNWs had ~40 times lower
      specific contact resistances (SCRs) of 5.9 * 10(-6) +/- 8.8 * 10(-6) Omega cm(2)
      compared to the values of Ti/Au ohmic contacts (2.6 * 10(-4) +/- 3.4 * 10(-4)
      Omega cm(2)). We also conducted a comparison study of the electrical
      characteristics of top-gated SiCNW field-effect transistors (FETs) with two
      different ohmic contacts as used for ohmic contact studies. The electrical
      transport measurements on the SiCNW FET with Ni/Au ohmic contacts show much lower
      resistance contacts to SiC NWs and better FET performances than those for Ti/Au
      ohmic contact-based FETs.

PMID- 21730642
TI  - A current-voltage model for Schottky-barrier graphene-based transistors.
AB  - A low complexity computational model of the current-voltage characteristics for
      graphene nanoribbon (GNR) field effect transistors (FET), being able to simulate
      a hundred points in a few seconds using a personal computer, is presented. For
      quantum capacitance controlled devices, self-consistent calculations of the
      electrostatic potential can be skipped. Instead, an analytical closed-form
      electrostatic potential from Laplace's equation yields accurate results compared
      with that obtained by the self-consistent non-equilibrium Green's functions
      (NEGF) method. The model includes both tunneling current through the Schottky
      barrier (SB) at the contact interfaces and thermionic current above the barrier,
      properly capturing the effect of arbitrary physical and electrical parameters.

PMID- 21730643
TI  - Wafer-scale patterning of sub-40 nm diameter and high aspect ratio (>50:1)
      silicon pillar arrays by nanoimprint and etching.
AB  - We demonstrate wide-area fabrication of sub-40 nm diameter, 1.5 um tall, high
      aspect ratio silicon pillar arrays with straight sidewalls by combining
      nanoimprint lithography (NIL) and deep reactive ion etching (DRIE). Imprint molds
      were used to pre-pattern nanopillar positions precisely on a 200 nm square
      lattice with long range order. The conventional DRIE etching process was modified
      and optimized with reduced cycle times and gas flows to achieve vertical
      sidewalls; with such techniques the pillar sidewall roughness can be reduced
      below 8 nm (peak-to-peak). In some cases, sub-50 nm diameter pillars, 3 um tall,
      were fabricated to achieve aspect ratios greater than 60:1.

PMID- 21730644
TI  - Convex and concave nanodots and lines induced on HOPG surfaces by AFM voltages in
      ambient air.
AB  - Convex and concave nanodots were created on highly oriented pyrolytic graphite
      (HOPG) in ambient air by applying a voltage pulse between a metal-coated atomic
      force microscope (AFM) tip and the sample surface. Using a linear scan with a
      positive substrate bias, nanoscale lines were also etched on the HOPG surface.
      Depending on the amplitude and duration of the voltage pulse, the nanostructures
      are either convex or concave. The depth of the concave structure sharply
      increased with the amplitude and duration of the voltage pulse, while the height
      of the convexity stayed at a low level and varied in a small range with the
      voltage lower than a threshold value. Under negative substrate bias or in a
      vacuum, no change occurred on the HOPG surface in the experimental range. The
      formation of the nanostructures can be ascribed to the primary dissociative
      adsorption of water and oxygen in air induced by the intensive hole concentration
      and the subsequent defect-assisted oxidation of graphite.

PMID- 21730645
TI  - Fabrication of high aspect ratio metal nanotips by nanosecond pulse laser
      melting.
AB  - The authors have developed an approach to fabricate sharp and high aspect ratio
      metal tips using nanosecond pulse laser melting. A quartz wafer covered with a
      thin chromium (Cr) film was placed on top of a second wafer with a sub-micrometer
      gap between them and the Cr film facing the second wafer. Then an excimer laser
      pulse (308 nm wavelength, 20 ns pulse duration) was shone from the back of the
      quartz wafer and melted the Cr film momentarily (several hundred nanoseconds). It
      is found that the molten Cr films can self-form discrete metal pillars connecting
      the two wafers. After separating the two wafers, nanotips were formed at the
      broken pillar necks. The sharpest tip achieved has an apex diameter 10 nm and
      height 180 nm. The self-formation of Cr pillars between the two wafers was
      attributed to the attractive electrostatic force caused by the work function
      difference of two wafers that were in close proximity. This technique could be
      extended to other metals, and a periodic uniform tip array could be obtained by
      pre-patterning the metal into identical isolated mesas and precisely controlling
      the gap between the two wafers.

PMID- 21730646
TI  - A generic approach for vertical integration of nanowires.
AB  - We report on the collective integration technology of vertically aligned
      nanowires (NWs). Si and ZnO NWs have been used in order to develop a generic
      technological process. Both mineral and organic planarizations of the as-grown
      nanowires have been achieved. Chemical vapour deposition (CVD) oxides, spin on
      glass (SOG), and polymer have been investigated as filling materials. Polishing
      and/or etching of the composite structures have been set up so as to obtain a
      suitable morphology for the top and bottom electrical contacts. Electrical and
      optical characterizations of the integrated NWs have been performed. Contacts
      ohmicity has been demonstrated and specific contact resistances have been
      reported. The photoconducting properties of polymer-integrated ZnO NWs have also
      been investigated in the UV-visible range through collective electrical contacts.
      A small increase of the resistivity in the ZnO NWs under sub-bandgap illumination
      has been observed and discussed. A comparison of the photoluminescence (PL)
      spectra at 300 K of the as-grown and SOG-integrated ZnO nanowires has shown no
      significant impact of the integration process on the crystal quality of the NWs.

PMID- 21730647
TI  - Single-photon emitting diode based on a quantum dot in a micro-pillar.
AB  - We have fabricated a single-photon emitting diode based on a quantum dot in a
      micro-pillar cavity. By temperature tuning the dot emission into resonance with
      the cavity mode we see an enhancement in the collected photon intensity at 40 K.
      We perform autocorrelation measurements on the electroluminescence at fixed bias,
      observing photon anti-bunching. Due to the low resistance and capacitance of our
      device we can inject current pulses shorter than the lifetime of the quantum
      state, producing single-photon emission with g((2))(0) = 0.17.

PMID- 21730648
TI  - A gold-nanoparticle-enhanced immune sensor based on fiber optic interferometry.
AB  - A method using gold nanoparticles (GNPs) to enhance fiber optic interferometry
      (GNPFOI) for immune-sensing is reported in this paper. It is suggested that an
      enlarged index mismatch and an elongated optical path by GNPs conjugated on
      recognition proteins will contribute most to signal enhancement in the
      interference fringe shift. Theoretical and experimental results show that the
      interference fringe shift is linearly related to both the amount and size of the
      GNPs binding on the sensor surface. The detected signal for 30 nm GNPs can reach
      a lowest detection limit of 18 pM (10(10) particles ml(-1)). Immune-sensing for
      rabbit IgG as the antigen to anti-rabbit IgG has been demonstrated and a
      detection cycle has been completed by elution buffer for surface regeneration.
      The repeatability of the immune-sensing on one GNPFOI sensor has also been
      verified by three identical cycles, and the detection limit for 13 nm GNPs
      conjugated anti-rabbit IgG reaches 0.17 nM (~25.5 ng ml(-1)). The sensory
      mechanism has the potential to be engineered on the tip of a needle-type micro
      device, which would allow it to monitor immune recognition signals in the future.

PMID- 21730649
TI  - Multi-walled carbon nanotube arrays for gas sensing applications.
AB  - Vertically aligned multi-walled carbon nanotube (MWCNT) arrays fabricated by
      xylene pyrolysis in anodized aluminum oxide (AAO) templates without the use of a
      catalyst were integrated into a resistive sensor design. Steady state
      sensitivities as high as 5% and 10% for 100 ppm of NH(3) and NO(2), respectively,
      at a flow rate of 750 sccm were observed. A thin layer of amorphous carbon (5-50
      nm), formed on both sides of the template during xylene pyrolysis, was part of
      the sensor design. The thickness of the conducting amorphous carbon layers was
      found to play a crucial role in determining the sensitivity of the resistive
      sensor. A study was undertaken to elucidate (i) the dependence of sensitivity on
      the thickness of amorphous carbon layers, (ii) the effect of UV light on gas
      desorption characteristics and (iii) the dependence of room temperature
      sensitivity on different NH(3) flow rates. Variations in sensor resistance with
      exposure to oxidizing and reducing gases are explained on the basis of charge
      transfer between the analytes and the CNTs which were modeled as p-type
      semiconductors.

PMID- 21730650
TI  - Surface energy-controlled in-plane growth of t-Se nanowires transformed from a-Se
      colloids.
AB  - This study investigated the surface energy-controlled transformation of amorphous
      Se (a-Se) colloids into trigonal Se (t-Se) crystals on solid substrates.
      Hydrophilic surfaces generated nanowires laterally grown along the surface of the
      substrates, while on hydrophobic surfaces the nanowires on the colloidal surface
      were randomly oriented. The ripening was considered to govern the growth of t-Se
      nanowires. The in-plane growth of the nanowires along the substrates made
      possible the creation of a chemically interconnected nanowire network because the
      nanowires made branches on meeting other a-Se colloids and formed chemical
      junctions on encountering other growing nanowires.

PMID- 21730651
TI  - Size-tunable near-infrared PbS nanoparticles synthesized from lead carboxylate
      and sulfur with oleylamine as stabilizer.
AB  - High quality PbS nanocrystals are synthesized reproducibly through lead stearate
      and sulfur stabilized by oleylamine in a non-coordinating solvent. The
      morphology, crystalline form and phase composition of PbS nanocrystals are
      examined by transmission electron microscopy (TEM), high-resolution TEM, x-ray
      diffraction (XRD), energy-dispersive x-ray spectroscopy (EDS) and x-ray
      photoelectron spectroscopy (XPS). The as-synthesized PbS nanocrystals have strong
      absorption and photoluminescence emissions in the near-infrared region. The size
      of PbS nanocrystals from 5 to 13 nm can be adjusted through the optimization of
      the synthesis conditions. The smaller PbS nanoparticles are obtained at the lower
      reaction temperature, lower precursor concentration, larger oleylamine quantity
      and larger lead precursor/sulfur ratio. The basic oleylamine enhances the
      reactivity of both lead stearate precursor and sulfur precursor in the reaction.

PMID- 21730652
TI  - Engineering the 3D architecture and hydrophobicity of methyltrichlorosilane
      nanostructures.
AB  - Three-dimensional nano-architectures with varying shape, morphology and size were
      fabricated by the phase separation of methyltrichlorosilane (CH(3)SiCl(3)) on
      commercially available glass and SiO(2) substrates. By changing the synthesis
      conditions, CH(3)SiCl(3) nanostructures evolved from discrete to quasi-network or
      from fibrous to spherical forms. Individual nanofibers and nanospheres have
      diameters of 18-90 and 240-300 nm, respectively, while the film thicknesses could
      reach 320 nm. The possible mechanisms for the three-dimensional growth of
      nanofibers and nanospheres are proposed. The resultant morphologies exhibited two
      main energy states: Wenzel and Cassie-Baxter states. Moreover, superhydrophobic
      surfaces with both high contact angle and high hysteresis resulted from the
      growth of the nanostructures. The new approaches presented herein are important
      additions to the current range of surface modification methods and could harness
      novel physical and chemical properties conducive to optimal performance in
      biosensing, antistiction, droplet manipulation, drag reduction, protein
      adsorption, and cell adhesion studies.

PMID- 21730653
TI  - Catalytic growth of metallic tungsten whiskers based on the vapor-solid-solid
      mechanism.
AB  - Metallic W whiskers with tip diameters of 50-250 nm and lengths of 2-4 um have
      been successfully synthesized in large quantities using Co-Ni alloyed catalysts.
      The relatively low growth temperature of 850  degrees C and the large catalyst
      size (over 100 nm) suggest that the growth of the W whiskers must be governed by
      the vapor-solid-solid mechanism. Our results show that the vapor-solid-solid
      model is suitable not only for the growth of nano-scaled whiskers with diameters
      below 100 nm, but also for submicro-scaled whiskers with diameters well above 100
      nm. This technique has great potential to synthesize well controlled metallic
      whiskers.

PMID- 21730654
TI  - A dual-colored bio-marker made of doped ZnO nanocrystals.
AB  - Bio-compatible ZnO nanocrystals doped with Co, Cu and Ni cations, surface capped
      with two types of aminosilanes and titania are synthesized by a soft chemical
      process. Due to the small particle size (2-5 nm), surface functional groups and
      the high photoluminescence emissions at the UV and blue-violet wavelength ranges,
      bio-imaging on human osteosarcoma (Mg-63) cells and histiocytic lymphoma U-937
      monocyte cells showed blue emission at the nucleus and bright turquoise emission
      at the cytoplasm simultaneously. This is the first report on dual-color bio
      images labeled by one semiconductor nanocrystal colloidal solution. Bright green
      emission was detected on mung bean seedlings labeled by all the synthesized ZnO
      nanocrystals. Cytotoxicity tests showed that the aminosilanes capped
      nanoparticles are non-toxic. Quantum yields of the nanocrystals varied from 79%
      to 95%. The results showed the potential of the pure ZnO and Co-doped ZnO
      nanocrystals for live imaging of both human cells and plant systems.

PMID- 21730655
TI  - An efficient and user-friendly method for the synthesis of hexagonal-phase
      NaYF(4):Yb, Er/Tm nanocrystals with controllable shape and upconversion
      fluorescence.
AB  - Hexagonal-phase NaYF(4):Yb, Er/Tm nanocrystals are the best IR-to-visible
      upconverting materials to date, but user-friendly methods for making pure
      hexagonal-phase NaYF(4):Yb, Er/Tm nanocrystals with upconversion fluorescence are
      still lacking. Most of the methods reported so far require excess fluoride
      reactants in a high-temperature reaction which are very unfriendly to users and
      raise safety concerns. In this work, an efficient and user-friendly method was
      developed for the synthesis of uniform hexagonal-phase NaYF(4):Yb, Er/Tm
      nanocrystals with upconversion fluorescence, by forming small solid-state crystal
      nuclei and further growth and ripening of the nuclei. NaYF(4):Yb, Er/Tm
      nanoplates, nanospheres and nanoellipses were also selectively produced by
      varying the concentration of the surfactant. All the nanocrystals showed strong
      upconversion fluorescence, and fluorescence from the nanoplates was observed even
      when the laser power density was reduced to about 50 mW cm(-2). These
      nanocrystals have great potential for use in biology and medicine as fluorescent
      labels or imaging probes.

PMID- 21730656
TI  - Coating multi-walled carbon nanotubes with rare-earth complexes by an in situ
      synthetic method.
AB  - Multi-walled carbon nanotubes (MWCNTs) were coated with rare-earth (RE) (Eu(3+),
      Tb(3+)) complex layers by a simple in situ synthetic method via noncovalently
      functionalized MWCNTs with sodium dodecyl sulfate. Extensive characterizations of
      the resulting nanocomposite materials have been performed using scanning electron
      microscopy (SEM), FT-IR spectra, x-ray diffraction (XRD), transmission electron
      microscopy (TEM), high-resolution transmission electron microscopy (HRTEM),
      energy-dispersive x-ray spectroscopy (EDS) and x-ray photoelectron spectroscopy
      (XPS). The photoluminescence properties of the RE-complex-modified MWCNTs were
      also investigated. Under the excitation of UV light, these samples exhibit
      characteristic emissions of Eu(3+) or Tb(3+) ions. The presence of the MWCNT
      framework does not quench the lanthanide-centered luminescence originating from
      the characteristic electronic transitions within the 4f shell of the RE ions.
      Furthermore, the existence of the nanotube framework can improve the stability of
      the RE complex under UV irradiation and elongate the fluorescence lifetime of the
      RE complex.

PMID- 21730657
TI  - Transport properties of alumina nanofluids.
AB  - Recent studies have showed that nanofluids have significantly greater thermal
      conductivity compared to their base fluids. Large surface area to volume ratio
      and certain effects of Brownian motion of nanoparticles are believed to be the
      main factors for the significant increase in the thermal conductivity of
      nanofluids. In this paper all three transport properties, namely thermal
      conductivity, electrical conductivity and viscosity, were studied for alumina
      nanofluid (aluminum oxide nanoparticles in water). Experiments were performed
      both as a function of volumetric concentration (3-8%) and temperature (2-50 
      degrees C). Alumina nanoparticles with a mean diameter of 36 nm were dispersed in
      water. The effect of particle size was not studied. The transient hot wire method
      as described by Nagaska and Nagashima for electrically conducting fluids was used
      to test the thermal conductivity. In this work, an insulated platinum wire of
      0.003 inch diameter was used. Initial calibration was performed using de-ionized
      water and the resulting data was within 2.5% of standard thermal conductivity
      values for water. The thermal conductivity of alumina nanofluid increased with
      both increase in temperature and concentration. A maximum thermal conductivity of
      0.7351 W m(-1) K(-1) was recorded for an 8.47% volume concentration of alumina
      nanoparticles at 46.6  degrees C. The effective thermal conductivity at this
      concentration and temperature was observed to be 1.1501, which translates to an
      increase in thermal conductivity by 22% when compared to water at room
      temperature. Alumina being a good conductor of electricity, alumina nanofluid
      displays an increasing trend in electrical conductivity as volumetric
      concentration increases. A microprocessor-based conductivity/TDS meter was used
      to perform the electrical conductivity experiments. After carefully calibrating
      the conductivity meter's glass probe with platinum tip, using a standard
      potassium chloride solution, readings were taken at various volumetric
      concentrations. A 3457.1% increase in the electrical conductivity was measured
      for a small 1.44% volumetric concentration of alumina nanoparticles in water. The
      highest value of electrical conductivity, 314 uS cm(-1), was recorded for a
      volumetric concentration of 8.47%. In the determination of the kinematic
      viscosity of alumina nanofluid, a standard kinematic viscometer with constant
      temperature bath was used. Calibrated capillary viscometers were used to measure
      flow under gravity at precisely controlled temperatures. The capillary
      viscometers were calibrated with de-ionized water at different temperatures, and
      the resulting kinematic viscosity values were found to be within 3% of the
      standard published values. An increase of 35.5% in the kinematic viscosity was
      observed for an 8.47% volumetric concentration of alumina nanoparticles in water.
      The maximum kinematic viscosity of alumina nanofluid, 2.901 42 mm(2) s(-1), was
      obtained at 0  degrees C for an 8.47% volumetric concentration of alumina
      nanoparticles. The experimental results of the present work will help researchers
      arrive at better theoretical models.

PMID- 21730658
TI  - The small length scale effect for a non-local cantilever beam: a paradox solved.
AB  - Non-local continuum mechanics allows one to account for the small length scale
      effect that becomes significant when dealing with microstructures or
      nanostructures. This paper presents some simplified non-local elastic beam
      models, for the bending analyses of small scale rods. Integral-type or gradient
      non-local models abandon the classical assumption of locality, and admit that
      stress depends not only on the strain value at that point but also on the strain
      values of all points on the body. There is a paradox still unresolved at this
      stage: some bending solutions of integral-based non-local elastic beams have been
      found to be identical to the classical (local) solution, i.e. the small scale
      effect is not present at all. One example is the Euler-Bernoulli cantilever
      nanobeam model with a point load which has application in microelectromechanical
      systems and nanoelectromechanical systems as an actuator. In this paper, it will
      be shown that this paradox may be overcome with a gradient elastic model as well
      as an integral non-local elastic model that is based on combining the local and
      the non-local curvatures in the constitutive elastic relation. The latter model
      comprises the classical gradient model and Eringen's integral model, and its
      application produces small length scale terms in the non-local elastic cantilever
      beam solution.

PMID- 21730659
TI  - Template synthesis, organic gas-sensing and optical properties of hollow and
      porous In(2)O(3) nanospheres.
AB  - Hollow and porous In(2)O(3) nanospheres have been prepared by the hydrolysis of
      InCl(3) using carbonaceous spheres as templates in combination with calcination.
      Based on the observation of scanning electronic microscopy (SEM) and transmission
      electron microscopy (TEM), it has been revealed that the as-prepared In(2)O(3)
      nanospheres have a uniform diameter of around 200 nm and hollow structures with
      thin shells of about 30 nm consisting of numerous nanocrystals and nanopores.
      Owing to the hollow and porous structures, In(2)O(3) nanospheres possessing more
      active surface area exhibit a good response and reversibility to some organic
      gases such as methanol, alcohol, acetone and ethyl ether. In addition, the
      response mechanism of hollow and porous In(2)O(3) nanospheres to organic gases
      has been proposed. Furthermore, these prepared In(2)O(3) spheres showed a UV
      visible absorption peak centered at around 309 nm, and their photoluminescence
      spectra have also been investigated.

PMID- 21730660
TI  - Mapping the positions of beads on a string: dethreading rotaxanes by molecular
      force spectroscopy.
AB  - The direct manipulation by atomic force microscopy (AFM) of individual
      macrocycles within a rotaxane offers a potential route to a new sequencing tool
      for complex macromolecules such as polysaccharides, glycoproteins and nucleic
      acids. In this paper we demonstrate for the first time that a sliding contact
      made between a macrocycle, alpha-cyclodextrin, and its polymer axle by an AFM tip
      can be used to map the positions of specific groups along the polymer as if they
      were beads along a string, thereby generating sequence information. We find very
      good agreement (linear fit with slope = 1.03, R(2) = 0.968) between the
      calculated and measured positions of phenylenediamine and benzenetricarboxylic
      acid groups within polymers of polyethylene oxide (PEO). The rupture force
      profiles attributable to the dethreading interactions of phenylenediamine and
      benzenetricarboxylic acid differ observably from each other and, in the latter
      case, from the rupture of the corresponding host-guest complex. As well as
      opening the way to a macromolecular sequencing technique, the ability
      demonstrated by this method to manipulate the dethreading of a rotaxane offers a
      new tool for investigating the process energetics in a wide array of
      spontaneously forming and forced rotaxane systems.

PMID- 21730661
TI  - Facile biosynthesis, separation and conjugation of gold nanoparticles to
      doxorubicin.
AB  - Particle shape and size determine the physicochemical and optoelectronic
      properties of nanoscale materials, including optical absorption, fluorescence,
      and electric and magnetic moments. It is thus desirable to be able to synthesize
      and separate various particle shapes and sizes. Biosynthesis using microorganisms
      has emerged as a more ecologically friendly, simpler, and more reproducible
      alternative to chemical synthesis of metal and semiconductor nanoparticles,
      allowing the generation of rare forms such as triangles. Here we show that the
      plant pathogenic fungus Helminthosporum solani, when incubated with an aqueous
      solution of chloroaurate ions, produces a diverse mixture of extracellular gold
      nanocrystals in the size range from 2 to 70 nm. A plurality are polydisperse
      spheres, but a significant number are homogeneously sized rods, triangles,
      pentagons, pyramids, and stars. The particles can be separated according to their
      size and shape by using a sucrose density gradient in a tabletop microcentrifuge,
      a novel and facile approach to nanocrystal purification. Conjugation to
      biomolecules can be performed without further processing, as illustrated with the
      smallest fraction of particles which were conjugated to the anti-cancer drug
      doxorubicin (Dox) and taken up readily into HEK293 cells. The cytotoxicity of the
      conjugates was comparable to that of an equivalent concentration of Dox.

PMID- 21730662
TI  - GFP expression by intracellular gene delivery of GFP-coding fragments using
      nanocrystal quantum dots.
AB  - Gene therapy is an attractive approach to supplement a deficient gene function.
      Although there has been some success with specific gene delivery using various
      methods including viral vectors and liposomes, most of these methods have a
      limited efficiency or also carry a risk for oncogenesis. We herein report that
      quantum dots (QDs) conjugated with nuclear localizing signal peptides (NLSP)
      successfully introduced gene-fragments with promoter elements, which promoted the
      expression of the enhanced green fluorescent protein (eGFP) gene in mammalian
      cells. The expression of eGFP protein was observed when the QD/gene-construct was
      added to the culture media. The gene-expression efficiency varied depending on
      multiple factors around QDs, such as (1) the reading direction of the gene
      fragments, (2) the quantity of gene-fragments attached on the surface of the QD
      constructs, (3) the surface electronic charges varied according to the structure
      of the QD/gene-constructs, and (4) the particle size of QD/gene complex varied
      according to the structure and amounts of gene-fragments. Using this QD/gene
      construct system, eGFP protein could be detected 28 days after the gene
      introduction whereas the fluorescence of QDs had disappeared. This system
      therefore provides another method for the intracellular delivery of gene
      fragments without using either viral vectors or specific liposomes.

PMID- 21730663
TI  - Electron emissions in InAs quantum dots containing a nitrogen incorporation
      induced defect state: the influence of thermal annealing.
AB  - With the incorporation of nitrogen (N) into InAs quantum dots (QDs), the carrier
      distribution near the QD displays electron emissions from a localized N-induced
      defect state at 0.34 eV and a weak emission at 0.15 eV from the QD. This defect
      state causes drastic carrier depletion in the neighboring GaAs bottom layer near
      the QD, which can effectively suppress tunneling emission for the QD excited
      states. As a result, electrons escape from the QD ground state through thermal
      emission to near the GaAs conduction band, rather than through thermal emission
      to the QD first excited state and a subsequent tunneling to the GaAs conduction
      band, as observed in InAs QDs without N incorporation. Thermal annealing can
      weaken the defect emission and enhance the QD emission, suggesting a removal of
      the defect state and a recovery of carriers in the QD. Increasing annealing
      temperature can significantly decrease the emission time and energy of the QD
      emission, which is explained by a weakening of tunneling suppression due to the
      removal of the defect state.

PMID- 21730664
TI  - Nanostructured organic-inorganic photodiodes with high rectification ratio.
AB  - High quality organic-inorganic heterojunction photodiodes based on nanostructured
      copper (II) phthalocyanine (CuPc) and intrinsic zinc oxide (i-ZnO) have been
      fabricated. The i-ZnO thin films/layers were grown by RF magnetron sputtering on
      clean indium tin oxide (ITO) coated glass substrates. These films have been
      characterized by optical absorption and field emission scanning electron
      microscopy (FESEM). CuPc thin films deposited at room temperature on i-ZnO have
      exhibited a change in their surface morphology with the post-deposition annealing
      temperature under normal atmosphere. The electrical dark conductivity and the
      photoconductivity of ITO/i-ZnO/CuPc/Au sandwich structures have been measured
      under various photoexcitation intensities using a xenon light source. The devices
      have shown excellent reproducibility of their electrical characteristics and high
      rectification ratios. The highest rectification ratio is nearly 831 calculated
      above the threshold voltage at room temperature for the sample annealed at 250 
      degrees C (i.e. Pc 250). The effects of the annealing temperature of CuPc on the
      surface morphology, rectification ratio, and optical properties have been
      discussed.

PMID- 21730665
TI  - Sub-wavelength ripples in fused silica after irradiation of the solid/liquid
      interface with ultrashort laser pulses.
AB  - Laser-induced backside wet etching (LIBWE) is performed using ultrashort 248 nm
      laser pulses with a pulse duration of 600 fs to obtain sub-wavelength laser
      induced periodic surface structures (LIPSS) on the back surface of fused silica
      which is in contact with a 0.5 mol l(-1) solution of pyrene in toluene. The LIPSS
      are strictly one-dimensional patterns, oriented parallel to the polarization of
      the laser radiation, and have a constant period of about 140 nm at all applied
      laser fluences (0.33-0.84 J cm(-2)) and pulse numbers (50-1000 pulses). The LIPSS
      amplitude varies due to the inhomogeneous fluence in the laser spot. The LIPSS
      are examined with scanning electron microscopy (SEM) and atomic force microscopy
      (AFM). Their power spectral density (PSD) distribution is analysed at a measured
      area of 10 um * 10 um. The good agreement of the measured and calculated LIPSS
      periods strongly supports a mechanism based on the interference of surface
      scattered and incident waves.

PMID- 21730666
TI  - Monoclinic beta-MoO(3) nanosheets produced by atmospheric microplasma:
      application to lithium-ion batteries.
AB  - Porous high surface area thin films of nanosheet-shaped monoclinic MoO(3) were
      deposited onto platinized Si substrates using patch antenna-based atmospheric
      microplasma processing. The films were characterized by high resolution
      transmission electron microscopy (HRTEM), scanning electron microscopy (SEM) and
      electrochemical analysis. The electrochemical analysis shows original redox peaks
      and high charge capacity, and also indicates a reversible electrochemical
      behaviour particularly beneficial for applications in Li-ion batteries. SEM shows
      that the films are highly porous and consist of nanosheets 50-100 nm thick with
      surface dimensions in the micrometre range. HRTEM reveals that the MoO(3)
      nanosheets consist of the monoclinic beta phase of MoO(3). These intricate
      nanoarchitectures made of monoclinic MoO(3) nanosheets have not been studied
      previously in the context of applications in Li-ion batteries and show superior
      structural and morphological features that enable effective insertion of Li ions.

PMID- 21730667
TI  - Physical adsorption on ferroelectric surfaces: photoinduced and thermal effects.
AB  - Selective deposition of charged polystyrene (PS) microspheres from an aqueous
      solution on domain-patterned lithium niobate is investigated. The selectivity of
      PS microsphere deposition can be varied by controlling the deposition
      temperature. Selective decoration of the positive domains (positive polarization
      surface charges) is achieved at room temperature and is attributed to the
      electrostatic interaction of the charged nanoparticles and the polarization
      surface charges of the ferroelectric. In contrast, at elevated temperatures, the
      particles decorate the negative domains. This process is explained by considering
      the pyroelectric properties of lithium niobate.

PMID- 21730668
TI  - Nanofabrication of PTCDA molecular chains on rutile TiO(2)(011)-(2 * 1) surfaces.
AB  - The adsorption of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) on a
      rutile TiO(2)(011)-(2 * 1) surface is studied using ultra-high vacuum scanning
      tunneling microscopy. The self-assembly process is dominated by the fine
      interplay between the lateral intermolecular interactions and the binding to the
      substrate. By means of temperature-induced change in the adsorption configuration
      and the activation of diffusion, the molecules are assembled into one-dimensional
      chains oriented along the [Formula: see text] crystallographic direction.

PMID- 21730669
TI  - Formation and characterization of nanotubes of La(OH)(3) obtained using porous
      alumina membranes.
AB  - An electrodeposition process is used to synthesize nanotubes of a lanthanum
      containing phase, employing porous alumina membranes as templates. This method
      should lead to the formation of La(OH)(3) nanowires, according to the previous
      results presented by Bocchetta et al (2007 Electrochem. Commun. 9 683-8), which
      can be decomposed to La(2)O(3), as the latter shows more interest for different
      applications. The results obtained by means of different electron microscopy
      techniques indicate that this method leads to the formation of nanotubes of about
      200 nm in diameter and 30-40 um in length, instead of the nanowires proposed in
      the literature. Additionally, the chemical characterization demonstrates that the
      material synthesized is composed of lanthanum hydroxycarbonate. The presence of
      carbonates is found to be crucial in determining the conditions for the
      preparation of La(2)O(3) from the nanotubes here obtained.

PMID- 21730670
TI  - Highly ordered hexagonally arranged nanostructures on silicon through a self
      assembled silicon-integrated porous anodic alumina masking layer.
AB  - A combined process of electrochemical formation of self-assembled porous anodic
      alumina thin films on a Si substrate and Si etching through the pores was used to
      fabricate ideally ordered nanostructures on the silicon surface with a long
      range, two-dimensional arrangement in a hexagonal close-packed lattice. Pore
      arrangement in the alumina film was achieved without any pre-patterning of the
      film surface before anodization. Perfect pattern transfer was achieved by an
      initial dry etching step, followed by wet or electrochemical etching of Si at the
      pore bottoms. Anisotropic wet etching using tetramethyl ammonium hydroxide (TMAH)
      solution resulted in pits in the form of inverted pyramids, while electrochemical
      etching using a hydrofluoric acid (HF) solution resulted in concave nanopits in
      the form of semi-spheres. Nanopatterns with lateral size in the range 12-200 nm,
      depth in the range 50-300 nm and periodicity in the range 30-200 nm were achieved
      either on large Si areas or on pre-selected confined areas on the Si substrate.
      The pore size and periodicity were tuned by changing the electrolyte for porous
      anodic alumina formation and the alumina pore widening time. This parallel large
      area nanopatterning technique shows significant potential for use in Si
      technology and devices.

PMID- 21730671
TI  - NaCl multi-layer islands grown on Au(111)-([Formula: see text]) probed by
      scanning tunneling microscopy.
AB  - The growth of multi-layer NaCl islands on Au(111)-([Formula: see text]) surfaces
      was investigated using scanning tunneling microscopy (STM). We observed that the
      aspect of the NaCl islands drastically differs depending on the tunneling
      conditions. It is therefore possible to observe the layers forming an NaCl island
      or to image the gold reconstruction below the first NaCl layer. Atomically
      resolved STM images obtained on the first NaCl layer demonstrate that NaCl grows
      as an epitaxial crystalline film on Au(111)-([Formula: see text]). STM images
      also suggest that some NaCl layers can be non-crystalline.

PMID- 21730672
TI  - Adiabatic pipelining: a key to ternary computing with quantum dots.
AB  - The quantum-dot cellular automaton (QCA), a processing platform based on
      interacting quantum dots, was introduced by Lent in the mid-1990s. What followed
      was an exhilarating period with the development of the line, the functionally
      complete set of logic functions, as well as more complex processing structures,
      however all in the realm of binary logic. Regardless of these achievements, it
      has to be acknowledged that the use of binary logic is in computing systems
      mainly the end result of the technological limitations, which the designers had
      to cope with in the early days of their design. The first advancement of QCAs to
      multi-valued (ternary) processing was performed by Lebar Bajec et al, with the
      argument that processing platforms of the future should not disregard the clear
      advantages of multi-valued logic. Some of the elementary ternary QCAs, necessary
      for the construction of more complex processing entities, however, lead to a
      remarkable increase in size when compared to their binary counterparts. This
      somewhat negates the advantages gained by entering the ternary computing domain.
      As it turned out, even the binary QCA had its initial hiccups, which have been
      solved by the introduction of adiabatic switching and the application of
      adiabatic pipeline approaches. We present here a study that introduces adiabatic
      switching into the ternary QCA and employs the adiabatic pipeline approach to
      successfully solve the issues of elementary ternary QCAs. What is more, the
      ternary QCAs presented here are sizewise comparable to binary QCAs. This in our
      view might serve towards their faster adoption.

PMID- 21730673
TI  - Finite size effect on hydrogen gas sensing performance in single Pd nanowires.
AB  - We present the hydrogen sensing performance of individual Pd nanowires grown by
      electrodeposition into nanochannels of anodized aluminum oxide (AAO) templates
      investigated as a function of the nanowire diameter. Four-terminal devices based
      on individual Pd nanowires were found to successfully detect hydrogen gas (H(2)).
      Our experimental results show that the H(2) sensing sensitivity increases and the
      response time decreases with decreasing diameter of Pd nanowires with d = 400,
      200, 80 and 20 nm, due to the high surface-to-volume ratio and short diffusion
      paths, respectively. This is in qualitatively good agreement with simulated
      results obtained from a theoretical model based on a combination of the rate
      equation and diffusion equation.

PMID- 21730674
TI  - Detection of gold nanoparticles using an immunoglobulin-coated piezoelectric
      sensor.
AB  - Since the existence of nanoparticles in our environment has already attracted
      considerable attention due to their possible toxic impact on biological systems,
      the field detection of nanoparticles is becoming a technology that will be much
      in need. We have constructed a piezoelectric sensor with an antibody-coated
      electrode. The antiserum can bind gold nanoparticles with a high degree of
      selectivity and sensitivity. The biosensor thus constructed can detect 4, 5, or 6
      nm gold nanoparticles (GNPs) depending on the coated antiserum. The sensitivity
      for the detection of 5 nm GNPs was 10.3 +/- 0.9 ng Hz(-1), with the low limit of
      detection at 5.5 ng. A quartz crystal microbalance (QCM) sensor was capable of
      detecting GNPs and other types of nanoparticle, such as ZnO, or Fe(3)O(4). The
      current study provides, for the first time, a platform for detecting
      nanoparticles in a convenient, economical manner.

PMID- 21730675
TI  - Rapid prototyping of nanotube-based devices using topology-optimized
      microgrippers.
AB  - Nanorobotic handling of carbon nanotubes (CNTs) using microgrippers is one of the
      most promising approaches for the rapid characterization of the CNTs and also for
      the assembly of prototypic nanotube-based devices. In this paper, we present pick
      and-place nanomanipulation of multi-walled CNTs in a rapid and a reproducible
      manner. We placed CNTs on copper TEM grids for structural analysis and on AFM
      probes for the assembly of AFM super-tips. We used electrothermally actuated
      polysilicon microgrippers designed using topology optimization in the
      experiments. The microgrippers are able to open as well as close. Topology
      optimization leads to a 10-100 times improvement of the gripping force compared
      to conventional designs of similar size. Furthermore, we improved our nanorobotic
      system to offer more degrees of freedom. TEM investigation of the CNTs shows that
      the multi-walled tubes are coated with an amorphous carbon layer, which is
      locally removed at the contact points with the microgripper. The assembled AFM
      super-tips are used for AFM measurements of microstructures with high aspect
      ratios.

PMID- 21730676
TI  - Size-controlled one-pot synthesis of fluorescent cadmium sulfide semiconductor
      nanoparticles in an apoferritin cavity.
AB  - A simple size-controlled synthesis of cadmium sulfide (CdS) nanoparticle (NP)
      cores in the cavity of apoferritin from horse spleen (HsAFr) was performed by a
      slow chemical reaction synthesis and a two-step synthesis protocol. We found that
      the CdS NP core synthesis was slow and that premature CdS NP cores were formed in
      the apoferritin cavity when the concentration of ammonia water was low. It was
      proven that the control of the ammonia water concentration can govern the CdS NP
      core synthesis and successfully produce size-controlled CdS NP cores with
      diameters from 4.7 to 7.1 nm with narrow size dispersion. X-ray powder
      diffraction (XRD), energy dispersive spectroscopy (EDS) analysis and high
      resolution transmission electron microscopy (HR-TEM) observation characterized
      the CdS NP cores obtained as cubic polycrystalline NPs, which showed
      photoluminescence with red shifts depending on their diameters. From the research
      of CdS NP core synthesis in the recombinant apoferritins, the zeta potential of
      apoferritin is important for the biomineralization of CdS NP cores in the
      apoferritin cavity. These synthesized CdS NPs with different photoluminescence
      properties will be applicable in a wide variety of nano-applications.

PMID- 21730677
TI  - Silver-plated carbon nanotubes for silver/conducting polymer composites.
AB  - Carbon nanotubes (CNTs) have advantages as conductive fillers due to their large
      aspect ratio and excellent conductivity. In this study, a novel silver/conducting
      polymer composite was developed by the incorporation of silver-plated CNTs. It is
      important to achieve a homogeneous dispersion of nanotubes and to improve the
      interfacial bonding to utilize the excellent properties of reinforcements in the
      matrix material. The homogeneous dispersion of nanotubes was achieved by an acid
      treatment process, and the interfacial contact was improved by electroless silver
      plating around nanotubes. The resistivity of the silver/conducting polymer
      composite was decreased by 83% by the addition of silver-plated single-walled
      carbon nanotubes. Conductive bumps were also screen-printed to demonstrate the
      capability of the composite as electrical interconnects for multi-layer printed
      circuit boards.

PMID- 21730678
TI  - Control of GaAs nanowire morphology and crystal structure.
AB  - The morphology and crystal structure of Au-seeded GaAs nanowires (NWs) grown by
      molecular beam epitaxy were investigated as a function of the temperature, V/III
      flux ratio, and Ga flux. Low and intermediate growth temperatures of 400 and 500 
      degrees C resulted in a strongly tapered morphology, with stacking faults
      occurring at an average rate of 0.1 nm(-1). NWs with uniform diameter and the
      occurrence of crystal defects reduced by more than an order of magnitude were
      achieved at 600  degrees C, a V/III flux ratio of 2.3, and a Ga impingement rate
      on the surface of 0.07 nm s(-1). Comparison of nanowire densities on the various
      post-growth surfaces suggests a possible incubation time between the moment the
      Ga shutter is opened and when nanowire growth is initiated. Increasing the flux
      ratio favored uniform sidewall growth, making the process suitable for the
      fabrication of core-shell structures.

PMID- 21730679
TI  - Preparation of poly(methyl methacrylate) grafted titanate nanotubes by in situ
      atom transfer radical polymerization.
AB  - This paper reports the successful preparation of core-shell hybrid nanocomposites
      by a 'grafting from' approach based on in situ atom transfer radical
      polymerization (ATRP) of methyl methacrylate (MMA) from titanate nanotubes
      (TNTs). Transmission electron microscope (TEM) images of the products provide
      direct evidence for the formation of a core-shell structure, possessing a hard
      core of TNTs and a soft shell of poly-MMA (PMMA). Fourier-transform infrared
      spectroscopy (FT-IR), hydrogen nuclear magnetic resonance ((1)H NMR), scanning
      electron microscopy (SEM), and thermal gravimetric analysis (TGA) were used to
      determine the chemical structure, morphology, and the grafted PMMA quantities of
      the resulting products. The grafted PMMA content was well controlled and
      increased with increasing monomer/initiator ratio. Further copolymerization of
      hydroxyethyl methacrylate (HEMA) with PMMA-coated TNTs as initiators was
      realized, illustrating the 'living' characteristics of the ATRP method used in
      this paper.

PMID- 21730680
TI  - Self-assembled hexagonal ordering of Si nanocrystals embedded in SiO(2) nanodots.
AB  - Highly dense hexagonally ordered two-dimensional arrays of Si nanocrystals
      embedded in SiO(2) nanodots were fabricated on a silicon substrate by using a
      self-assembled porous anodic alumina thin film as a masking layer through which
      electrochemical oxidation of the Si substrate and ultralow energy Si implantation
      took place. After removal of the alumina film and high temperature annealing of
      the samples, hexagonally ordered Si nanocrystals embedded within SiO(2) nanodots
      were obtained, having sizes in the few tens of nanometer range. The fabricated
      ordered structures show significant potential for applications either in basic
      physics experiments or as building blocks for nanoelectronic and nanophotonic
      devices.

PMID- 21730681
TI  - In-plane conductance measurement of graphene nanoislands using an integrated
      nanogap probe.
AB  - The in-plane conductance of individual graphene nanoislands thermally grown on
      SiC substrate was successfully measured using an integrated nanogap probe without
      lithographic patterning. A Pt nanogap electrode with a 30 nm gap integrated on
      the cantilever tip of a scanning probe microscope enables us to image a
      conductance map of graphene nanoislands with nanometer resolution. Single- and
      double-layer graphene islands are clearly distinguished in the conductance image.
      The size dependence of the conductance of the nanoislands suggests that the band
      gap opening is due to the lateral confinement effect.

PMID- 21730682
TI  - Electrical breakdown and nanogap formation of indium oxide core/shell
      heterostructure nanowires.
AB  - We report the electrical breakdown behavior and subsequent nanogap formation of
      In(2)O(3)/InO(x) core/shell heterostructure nanowires with substrate-supported
      and suspended structures. The radial heterostructure nanowires, composed of
      crystalline In(2)O(3) cores and amorphous In-rich shells, are grown by chemical
      vapor deposition. As the nanowires broke down, they exhibited two distinct
      current drops in the current-voltage characteristics. The tips of the broken
      nanowires were found to have a cone or a volcano shape depending on the width of
      the nanowire. The shape, the size, and the position of the nanogap depend
      strongly on the device structure and the nanowire dimensions. The substrate
      supported and the suspended devices exhibit distinct breakdown behavior which can
      be explained by the diffusive thermal transport model. The breakdown temperature
      of the nanowire is estimated to be about 450 K, close to the melting temperature
      of indium. We demonstrated the usefulness of this technique by successful
      fabrication of working pentacene field-effect transistors.

PMID- 21730683
TI  - Nanoscale thermal-mechanical probe determination of 'softening transitions' in
      thin polymer films.
AB  - We report a quantitative study of the softening behavior of glassy polystyrene
      (PS) films at length scales on the order of 100 nm using nano-thermomechanometry
      (nano-TM), an emerging scanning probe technique in which a highly doped silicon
      atomic force microscopy (AFM) tip is resistively heated on the surface of a
      polymer film. The apparent 'softening temperature' T(s) of the film is found to
      depend on the logarithm of the square root of the thermal ramping rate R. This
      relation allows us to estimate a quasi-equilibrium (or zero rate) softening
      transition temperature T(s0) by extrapolation. We observe marked shifts of T(s0)
      with decreasing film thickness, but the nature of these shifts, and even their
      sign, depend strongly on both the thermal and mechanical properties of the
      supporting substrate. Finite element simulations suggest that thin PS films on
      rigid substrates with large thermal conductivities lead to increasing T(s0) with
      decreasing film thickness, whereas softer, less thermally conductive substrates
      promote reductions in T(s0). Experimental observations on a range of substrates
      confirm this behavior and indicate a complicated interplay between the thermal
      and mechanical properties of the thin PS film and the substrate. This study
      directly points to relevant factors for quantitative measurements of
      thermophysical properties of materials at the nanoscale using this nano-TM based
      method.

PMID- 21730684
TI  - A new atomic force microscope force ramp technique using digital force feedback
      control reveals mechanically weak protein unfolding events.
AB  - We have developed a new force ramp modification of the atomic force microscope
      (AFM) which can control multiple unfolding events of a multi-modular protein
      using software-based digital force feedback control. With this feedback the force
      loading rate can be kept constant regardless the length of soft elastic linkage
      or number of unfolded polypeptide domains. An unfolding event is detected as a
      sudden drop in force, immediately after which the feedback control reduces the
      applied force to a low value of a few pN by lowering the force set point. Hence
      the remaining folded domains can relax and the subsequent force ramp is applied
      to relaxed protein domains identically in each case. We have applied this
      technique to determine the kinetic parameters x(u), which is the distance between
      the native state and transition state, and alpha(0), which is the unfolding rate
      constant at zero force, for the mechanical unfolding of a pentamer of I27 domains
      of titin. In each force ramp the unfolding probability depends on the number of
      folded domains remaining in the system and we had to take account of this effect
      in the analysis of unfolding force data. We obtained values of x(u) and alpha(0)
      to be 0.28 nm and 1.02 * 10(-3) s(-1), which are in good agreement with those
      obtained from conventional constant velocity experiments. This method reveals
      unfolding data at low forces that are not seen in constant velocity experiments
      and corrects for the change in stiffness that occurs with most mechanical systems
      throughout the unfolding process to allow constant force ramp experiments to be
      carried out. In addition, a mechanically weak structure was detected, which
      formed from the fully extended polypeptide chain during a force quench. This
      indicates that the new technique will allow studies of the folding kinetics of
      previously hidden, mechanically weak species.

PMID- 21730685
TI  - Multiple radial corrugations in multiwalled carbon nanotubes under pressure.
AB  - Radial elastic corrugation of multiwalled carbon nanotubes under hydrostatic
      pressure is demonstrated by using the continuum elastic theory. Various
      corrugation patterns are observed under a pressure of several GPa, wherein the
      stable cross-sectional shape depends on the innermost tube diameter D and the
      total number N of concentric walls. A phase diagram is established to obtain the
      requisite values of D and N for a desired corrugation pattern among choices. In
      all corrugation patterns, the cylindrical symmetry of the innermost tube is
      maintained even under high external pressure.

PMID- 21730686
TI  - Enhanced ionic conductivity of AgI nanowires/AAO composites fabricated by a
      simple approach.
AB  - AgI nanowires/anodic aluminum oxide (AgI NWs/AAO) composites have been fabricated
      by a simple approach, which involves the thermal melting of AgI powders on the
      surface of the AAO membrane, followed by the infiltration of the molten AgI
      inside the nanochannels. As-prepared AgI nanowires have corrugated outer surfaces
      and are polycrystalline according to scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) observations. X-ray diffraction (XRD)
      shows that a considerable amount of 7H polytype AgI exists in the composites,
      which is supposed to arise from the interfacial interactions between the embedded
      AgI and the alumina. AC conductivity measurements for the AgI nanowires/AAO
      composites exhibit a notable conductivity enhancement by three orders of
      magnitude at room temperature compared with that of pristine bulk AgI.
      Furthermore, a large conductivity hysteresis and abnormal conductivity
      transitions were observed in the temperature-dependent conductivity measurements,
      from which an ionic conductivity as high as 8.0 * 10(2) Omega(-1) cm(-1) was
      obtained at around 70  degrees C upon cooling. The differential scanning
      calorimetry (DSC) result demonstrates a similar phase transition behavior as that
      found in the AC conductivity measurements. The enhanced ionic conductivity, as
      well as the abnormal phase transitions, can be explained in terms of the
      existence of the highly conducting 7H polytype AgI and the formation of well
      defined conduction paths in the composites.

PMID- 21730687
TI  - Enhanced dispersion of carbon nanotubes in hyperbranched polyurethane and
      properties of nanocomposites.
AB  - Hyperbranched polyurethane (HBPU) nanocomposites with multi-walled carbon
      nanotubes (MWNTs) were prepared by in situ polymerization on the basis of
      poly(epsilon-caprolactone)diol as the soft segment, 4,4'-methylene
      bis(phenylisocyanate) as the hard segment, and castor oil as the multifunctional
      group for the hyperbranched structure. A dominant improvement in the dispersion
      of MWNTs in the HBPU matrix was found, and good solubility of HBPU-MWNT
      nanocomposites in organic solvents was shown. Due to the well-dispersed MWNTs,
      the nanocomposites resulted in achieving excellent shape memory properties as
      well as enhanced mechanical properties compared to pure HBPU.

PMID- 21730688
TI  - Thermal effect on DWCNTs as rotational bearings.
AB  - We have investigated the rotational motion and dynamic friction in a molecular
      bearing composed of double-walled carbon nanotubes (DWCNTs) using molecular
      dynamics simulations. The main study was on thermal effects due to the rotational
      friction. The diameters of the bearings varied between 6 and 16 A for the inner
      shafts, and between 12 and 20 A for the outer sleeves. The rotation velocity
      varied from 0.05 rotations ps(-1) to 0.25 rotations ps(-1). The simulations show
      that the energy dissipation, and hence the temperature of the system, increases
      linearly with rotation time. The value of energy dissipation is around 0.59
      meV/atom per rotation at omega = 0.05 rotations ps(-1) for a (15, 0)@(23, 0)
      bearing. Correspondingly, the average friction force is around 1.75 * 10(-5)
      nN/atom. The dependence of the energy dissipation on the rotation velocity, the
      interwall distance, and the contact area of the DWCNT is also discussed. It was
      observed that the energy dissipation becomes lowest when the interwall distance
      of the DWCNT bearing reaches about 0.34 nm, the equilibrium distance of the
      Lennard-Jones (L-J) potential. This low energy dissipation suggests that the
      DWCNT can be a good candidate for a wearless rotational bearing, which supports
      the previous studies.

PMID- 21730689
TI  - Synthesis and characterization of a new trifunctional magnetic-photoluminescent
      oxygen-sensing nanomaterial.
AB  - Magnetic Fe(2)O(3) nanoparticles coated with SiO(2) chemically doped with a
      Ru(II) complex were prepared using a simple solution based method. Field-emission
      scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM)
      showed that the Fe(2)O(3) nanoparticles with a mean diameter of ~115 nm were
      successfully coated with Ru(II) complex-chemically doped SiO(2) shell with a
      thickness of ~30 nm. The obtained nanocomposite material showed a strong magnetic
      response to a varying magnetic field, exhibited the bright red triplet metal-to
      ligand charge transfer ((3)MLCT) emission, and its photoluminescent intensity was
      sensitive to oxygen concentration. Compared with the Ru(II) complex in silica
      gels, the Ru(II) complex in the magnetic-optical-oxygen-sensing nanocomposite
      demonstrated improved thermodynamic stability of emissions. These nanocomposites
      are also nontoxic and easily conjugated with biomolecules. Their magnetic,
      photoluminescent and oxygen-sensing properties make them promising candidates for
      cell separation, biomarkers and optical oxygen sensors, which can measure the
      O(2) concentration in biological bodies.

PMID- 21730690
TI  - Bending fracture in carbon nanotubes.
AB  - A novel approach was adopted to incur bending fracture in carbon nanotubes
      (CNTs). Expanded graphite (EG) was made by intercalating and exfoliating natural
      graphite flakes. The EG was deposited with nickel particles, from which CNTs were
      grown by chemical vapor deposition. The CNTs were tip-grown, and their roots were
      fixed on the EG flakes. The EG flakes were compressed, and many CNTs on the
      surface were fragmented due to the compression-induced bending. Two major modes
      of the bending fracture were observed: cone-shaped and shear-cut. High-resolution
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
      were used to examine the crack growth within the graphene layers. The bending
      fracture is characterized by two-region crack growth. An opening crack first
      appears around the outer-tube due to the bending-induced tensile stress. The
      crack then branches to grow along an inclined direction toward the inner-tube due
      to the presence of the shear stress in between graphene layers. An inner-tube
      pullout with inclined side surface is formed. The onset and development of the
      crack in these two regions are discussed.

PMID- 21730691
TI  - One-pot fabrication and magnetic studies of Mn-doped TiO(2) nanocrystals with an
      encapsulating carbon layer.
AB  - Mn-doped TiO(2) nanocrystals encapsulated in a carbon layer (Ti(1-x)Mn(x)O(2)@C)
      were synthesized by the one-pot RAPET (reaction under autogenic pressure at
      elevated temperature) technique. Manganese was doped into the body-centered
      tetragonal TiO(2) anatase phase to give a Mn:Ti atomic ratio of 1%, 5% and 10%.
      The surface modification by carbon was achieved in order to make the
      cubic/tetragonal nanocrystals non-toxic and biocompatible. Electron paramagnetic
      resonance (EPR) studies revealed a broad resonance (centered at g = 1.9977 due to
      the interacting spins in the oxide matrix) with increased dopant concentration
      and the resonance due to carbon. Manganese is mainly present as +II or +III
      oxidation states. The magnetic behavior was found to be very dependent on the
      manganese concentration with a ferromagnetic behavior of the 1% doped sample due
      to the coupling between carriers and manganese spins. A predominant paramagnetic
      behavior was observed for the higher Mn-doped samples. This study opens up a new
      dimension for the carbon encapsulation of room-temperature ferromagnetic diluted
      magnetic semiconductor (DMS) nanomaterials.

PMID- 21730692
TI  - Core and shell sizing of small silver-coated nanospheres by optical extinction
      spectroscopy.
AB  - Silver metal nanoparticles (Nps) are extensively used in different areas of
      research and technology due to their interesting optical, thermal and electric
      properties, especially for bare core and core-shell nanostructures with sizes
      smaller than 10 nm. Since these properties are core-shell size-dependent, size
      measurement is important in manipulating their potential functionalization and
      applications. Bare and coated small silver Nps fabricated by physical and
      chemical methods present specific characteristics in their extinction spectra
      that are potentially useful for sizing purposes. This work presents a novel
      procedure to size mean core radius smaller than 10 nm and mean shell thickness of
      silver core-shell Nps based on a comparative study of the characteristics in
      their optical extinction spectra in different media as a function of core radii,
      shell thickness and coating refractive index. From the regularities derived from
      these relationships, it can be concluded that plasmon full width at half-maximum
      (FWHM) is sensitive to core size but not to coating thickness, while plasmon
      resonance wavelength (PRW) is related to shell thickness and mostly independent
      of core radius. These facts, which allow sizing simultaneously both mean core
      radius and shell thickness, can also be used to size bare silver Nps as a special
      case of core-shell Nps with zero shell thickness. The proposed method was applied
      to size experimental samples and the results show good agreement with
      conventional TEM microscopy.

PMID- 21730693
TI  - A method to quantitatively measure the elastic modulus of materials in nanometer
      scale using atomic force microscopy.
AB  - A method is proposed for quantitatively measuring the elastic modulus of
      materials using atomic force microscopy (AFM) nanoindentation. In this method,
      the cantilever deformation and the tip-sample interaction during the early
      loading portion are treated as two springs in series, and based on Sneddon's
      elastic contact solution, a new cantilever-tip property alpha is proposed which,
      together with the cantilever sensitivity A, can be measured from AFM tests on two
      reference materials with known elastic moduli. The measured alpha and A values
      specific to the tip and machine used can then be employed to accurately measure
      the elastic modulus of a third sample, assuming that the tip does not get
      significantly plastically deformed during the calibration procedure. AFM
      nanoindentation tests were performed on polypropylene (PP), fused quartz and
      acrylic samples to verify the validity of the proposed method. The cantilever-tip
      property and the cantilever sensitivity measured on PP and fused quartz were
      0.514 GPa and 51.99 nm nA(-1), respectively. Using these measured quantities, the
      elastic modulus of acrylic was measured to be 3.24 GPa, which agrees well with
      the value measured using conventional depth-sensing indentation in a commercial
      nanoindenter.

PMID- 21730694
TI  - Electronic structure and self-assembly of cross-linked semiconductor nanocrystal
      arrays.
AB  - We studied the electronic level structure of assemblies of InAs quantum dots and
      CdSe nanorods cross-linked by 1,4-phenylenediamine molecules using scanning
      tunneling spectroscopy. We found that the bandgap in these arrays is reduced with
      respect to the corresponding ligand-capped nanocrystal arrays. In addition, a
      pronounced sub-gap spectral structure commonly appeared which can be attributed
      to unpassivated nanocrystal surface states or associated with linker-molecule
      related levels. The exchange of the ligands by the linker molecules also affected
      the structural array properties. Most significantly, clusters of close-packed
      standing CdSe nanorods were formed.

PMID- 21730695
TI  - A network model to correlate conformational change and the impedance spectrum of
      single proteins.
AB  - Integrated nanodevices based on proteins or biomolecules are attracting
      increasing interest in today's research. In fact, it has been shown that proteins
      such as azurin and bacteriorhodopsin manifest some electrical properties that are
      promising for the development of active components of molecular electronic
      devices. Here we focus on two relevant kinds of protein: bovine rhodopsin,
      prototype of G-protein-coupled-receptor (GPCR) proteins, and the enzyme
      acetylcholinesterase (AChE), whose inhibition is one of the most qualified
      treatments of Alzheimer's disease. Both these proteins exert their function
      starting with a conformational change of their native structure. Our guess is
      that such a change should be accompanied with a detectable variation of their
      electrical properties. To investigate this conjecture, we present an impedance
      network model of proteins, able to estimate the different impedance spectra
      associated with the different configurations. The distinct types of
      conformational change of rhodopsin and AChE agree with their dissimilar
      electrical responses. In particular, for rhodopsin the model predicts variations
      of the impedance spectra up to about 30%, while for AChE the same variations are
      limited to about 10%, which supports the existence of a dynamical equilibrium
      between its native and complexed states.

PMID- 21730696
TI  - The effects of oxygen on the surface passivation of InP nanowires.
AB  - The effects of surface passivation on the electronic and structural properties of
      InP nanowires have been investigated by first-principles calculations. We compare
      the properties of nanowires whose surfaces have been passivated in several ways,
      always by H atoms and OH radicals. Taking as the initial reference nanowires that
      are fully passivated by H atoms, we find that the exchange of these atoms at the
      surface by OH radicals is always energetically favorable. A nanowire fully
      passivated by OH radicals is about 2.5 eV per passivated dangling bond more
      stable than a nanowire fully passivated by H atoms. However, the energetically
      most stable passivated surface is predicted to have all In atoms bonded to OH
      radicals and all P atoms bonded to H atoms. This mixed passivation is 2.66 eV per
      passivated dangling bond more stable than a nanowire fully passivated by H atoms.
      Our results show that, in comparison with the fully H-saturated nanowire, the
      fully OH-saturated nanowire has a smaller energy band gap and localized states
      near the energy band edges. Also, more interestingly, concerning optical
      applications, the most stable H+OH passivated nanowire has a well-defined energy
      band gap, only 10% smaller than the H-saturated nanowire energy gap, and few
      localized states always close to the valence band maximum.

PMID- 21730697
TI  - Kondo effect by controlled cleavage of a single-molecule contact.
AB  - Conductance measurements of a molecular wire, contacted between an epitaxial
      molecule-metal bond and the tip of a scanning tunnelling microscope, are
      reported. Controlled retraction of the tip gradually de-hybridizes the molecule
      from the metal substrate. This tunes the wire into the Kondo regime in which the
      renormalized molecular transport orbital serves as a spin impurity at half
      filling and the Kondo resonance opens up an additional transport channel.
      Numerical renormalization group simulations suggest this type of behaviour to be
      generic for a common class of metal-molecule bonds. The results demonstrate a new
      approach to single-molecule experiments with atomic-scale contact control and
      prepare the way for the ab initio simulation of many-body transport through
      single-molecule junctions.

PMID- 21730698
TI  - Transport properties of graphene nanoribbons with side-attached organic
      molecules.
AB  - In this work we address the effects on the conductance of graphene nanoribbons
      (GNRs) of organic molecules adsorbed at the ribbon edge. We studied the case of
      armchair and zigzag GNRs with quasi-one-dimensional side-attached molecules, such
      as linear poly-aromatic hydrocarbons and poly(para-phenylene). These
      nanostructures are described using a single-band tight-binding Hamiltonian and
      their electronic conductance and density of states are calculated within the
      Green's function formalism based on real-space renormalization techniques. We
      found that the conductance exhibits an even-odd parity effect as a function of
      the length of the attached molecules. Furthermore, the corresponding energy
      spectrum of the molecules can be obtained as a series of Fano antiresonances in
      the conductance of the system. The latter result suggests that GNRs can be used
      as a spectrograph sensor device.

PMID- 21730699
TI  - Selective growth of boron nitride nanotubes by plasma-enhanced chemical vapor
      deposition at low substrate temperature.
AB  - Hexagonal boron nitride nanotubes (BNNTs) were synthesized at a low substrate
      temperature of 800  degrees C on nickel (Ni) coated oxidized Si(111) wafers in a
      microwave plasma-enhanced chemical vapor deposition system (MPCVD) by
      decomposition and reaction of gas mixtures consisting of B(2)H(6)-NH(3)-H(2). The
      1D BN nanostructures grew preferentially on Ni catalyst islands with a small
      thickness only. In situ mass spectroscopic analysis and optical emission
      spectroscopy were used to identify the gas reactions responsible for the BNNT
      formation. The morphology and structural properties of the deposits were analyzed
      by SEM, TEM, EDX, SAD and Raman spectroscopy. The growth mechanism of the BNNTs
      was identified.

PMID- 21730700
TI  - Room temperature synthesis of rod-like FeC(2)O(4).2H(2)O and its transition to
      maghemite, magnetite and hematite nanorods through controlled thermal
      decomposition.
AB  - FeC(2)O(4).2H(2)O nanorods with diameter of about 50 nm and length of up to
      several micrometers were synthesized at room temperature in a surfactant-assisted
      system, which was obtained by dissolving bis(2-ethylhexyl)sodium sulfosuccinate
      (AOT) in a mixed solution composed of water and ethylene glycol (EG). The
      influence of reaction conditions on the morphology of FeC(2)O(4).2H(2)O is
      discussed in detail. Through direct thermal decomposition of FeC(2)O(4).2H(2)O
      under different calcination conditions, maghemite (gamma-Fe(2)O(3)), magnetite
      (Fe(3)O(4)) and hematite (alpha-Fe(2)O(3)) can be selectively obtained,
      preserving the rod-like morphology. Transmission electron microscope (TEM) and
      high-resolution transmission electron microscope (HRTEM) characterizations showed
      that the as-obtained iron oxide nanorods were composed of fine particles with
      different crystal orientations. The magnetic properties of the as-obtained iron
      oxide nanorods were systematically investigated.

PMID- 21730701
TI  - Preparation and characterization of nanometric Mn ferrite via different methods.
AB  - The structure and magnetic properties of MnFe(2)O(4) ferrites have been
      investigated using five different preparation methods, including the ceramic
      technique, flash combustion, co-precipitation, sol-gel and citrate methods. The
      characteristics of one sample prepared by different methods have been studied to
      select the better method, i.e. the one that is the simplest and does not require
      an elaborate instrumental set-up. The results indicated that the citrate method
      gives the lowest value for the lattice parameter and particle size (14.1 nm),
      while the highest values are obtained with the ceramic method. The smallest
      nanosizes were obtained in the citrate and flash methods (14.1 and 40.7 nm,
      respectively).

PMID- 21730702
TI  - Polyelectrolyte mediated scalable synthesis of highly stable silver nanocubes in
      less than a minute using microwave irradiation.
AB  - Silver nanocubes were synthesized for the first time in large quantities on gold
      seed in the presence of a polyelectrolyte using microwave heating for 60-120 s.
      Our experiment indicates that the polyelectrolyte directs the growth of the
      particle in a specified crystallographic direction resulting in the faceted
      particle, i.e. a nanocube. The nanocubes are stable for at least 2 months in
      ambient conditions.

PMID- 21730703
TI  - Enhanced field emission from aligned multistage carbon nanotube emitter arrays.
AB  - In this work we report on the synthesis and field emission properties of carbon
      nanotube multistage emitter arrays grown on porous silicon by catalytic thermal
      chemical vapor deposition. The vertically oriented multistage array structures
      consisted of SWNTs and thin MWNTs grown on MWNTs, confirmed by TEM and Raman
      analysis. Higher field emission current ~32 times and low threshold field ~1.5
      times were obtained for these structures in comparison to only MWNT arrays. The
      enhanced field emission results for these multistage emitters are a consequence
      of higher field concentration, which is ~3 times more than MWNTs.

PMID- 21730704
TI  - Direct synthesis of ZnO nanowire arrays on Zn foil by a simple thermal
      evaporation process.
AB  - ZnO nanowire arrays were synthesized on zinc foil by a simple thermal evaporation
      process at relatively low temperature. Morphology and size controlled synthesis
      of the ZnO nanostructures was achieved by variation of the synthesis temperature,
      reaction time and the surface roughness of the substrate. A gas-solid and self
      catalytic liquid-solid mechanism is proposed for the growth of nanowires at
      different temperatures. High-resolution transmission electron microscopy (HRTEM)
      showed that the as-grown nanowires were of single crystal hexagonal wurtzite
      structure, growing along the [101] direction. Photoluminescence exhibited strong
      UV emission at ~382 nm and a broad green emission at ~513 nm with 325 nm
      excitation. Raman spectroscopy revealed a phonon confinement effect when compared
      with results from bulk ZnO. The nanowire arrays also exhibited a field emission
      property.

PMID- 21730705
TI  - A facile solution-phase approach to the synthesis of luminescent europium
      methacrylate nanowires and their thermal conversion into europium oxide
      nanotubes.
AB  - Novel one-dimensional (1D) nanostructures of rare earth complexes (europium
      methacrylate (Eu(MA)(3))) have been prepared from the precursor of irregularly
      shaped Eu(MA)(3) powder in ethanol solvent without the assistance of an added
      surfactant, catalyst, or template. These hexagonal-shaped complex nanowires have
      diameters of about 100-300 nm and lengths ranging from tens to hundreds of
      micrometers. Nuclear magnetic resonance (NMR) spectroscopy, Fourier transform
      infrared (FTIR) studies and thermogravimetric analysis (TGA) show that the
      precursor powder and the resulting nanowires have identical compositions. Under
      UV light excitation, strong red fluorescence can be clearly seen throughout the
      whole wires. This good luminescence characteristic of the complex nanowires is
      further confirmed by the fluorescence spectrum where strong and narrow emission
      can be seen. These rare earth complex nanowires provide a useful source for 1D
      rare earth oxide materials, as the europium ions are distributed uniformly in the
      Eu(MA)(3) nanowires. Through calcination, the Eu(MA)(3) nanowires are
      successfully converted into Eu(2)O(3) nanotubes. X-ray investigation confirms
      that the Eu(2)O(3) nanotubes have a cubic body-centered structure. FTIR
      measurements and TGA analysis are used to follow the calcination process. A
      plausible mechanism responsible for the formation of Eu(2)O(3) nanotubes is
      presented.

PMID- 21730706
TI  - Growth of SiO(x) nanowires by laser ablation.
AB  - Amorphous SiO(x) nanowires (NWs) were synthesized using laser ablation of silicon
      containing targets. The influence of various parameters such as target
      composition, substrate type, substrate temperature and carrier gas on the growth
      process was studied. The NWs were characterized using high resolution scanning
      and transmission electron microscopes (HRSEM and HRTEM) with their attachments:
      electron dispersive spectroscopy (EDS) and energy electron loss spectroscopy
      (EELS). A metal catalyst was found essential for the NW growth. A growth
      temperature higher than 1000  degrees C was necessary for the NW formation using
      an Ar-based carrier gas at 500 Torr. The use of Ar-5%H(2) instead of pure Ar
      resulted in a higher yield and longer NWs. Application of a diffusion barrier on
      top of the Si substrate guaranteed the availability of metal catalyst droplets on
      the surface, essential for the NW growth. Ni was found to be a better catalyst
      than Au in terms of the NW yield and length. Two alternative sequences for the
      evolution of the amorphous SiO(x) NWs were considered: (a) the formation of Si
      NWs first and their complete oxidation afterwards, which seems to be doubtful,
      (b) the direct formation of SiO(x) NWs, which is more likely to occur. The direct
      formation mechanism was proposed to advance in three stages: preferential
      adsorption of SiO(x) clusters on the catalyst surface first, a successive surface
      diffusion to the catalyst droplet lower hemisphere, and finally the formation and
      growth of the NW between the catalyst and the substrate.

PMID- 21730707
TI  - Assembly behavior and monolayer characteristics of OH-terminated alkanethiol on
      Au(111): in situ scanning tunneling microscopy and electrochemical studies.
AB  - Self-assembled monolayers (SAMs) of 6-mercapto-1-hexanol (MHO) on an Au(111)
      electrode were prepared in an electrochemical system. The adsorption behavior of
      MHO and the time-dependent organization of the SAM were investigated by in situ
      scanning tunneling microscopy (STM) and cyclic voltammetry (CV). The results show
      that a potential higher than 0.28 V (relative to RHE) is required to induce the
      adsorption of MHO. At 0.28 V, the MHO molecules adsorb in a flat-lying
      orientation, forming an ordered striped phase with a molecular arrangement of
      ([Formula: see text]). However, the adlayer is not stable at this potential. The
      adsorbed striped phase may recover to the herringbone feature of the gold
      substrate due to the desorption of adsorbed MHO. At a higher potential (0.35 V),
      the adlayer becomes stable and can undergo a phase evolution from the striped
      phase to a condensed structure, identified as c([Formula: see text]). This
      structure can also be described as a c(4 * 2) superlattice of a [Formula: see
      text] hexagonal adlattice. The surface coverage of the MHO SAM is identical to
      the saturated structure of an 11-mercapto-1-undecanol (MUO) SAM reported in a
      previous work, [Formula: see text]. However, the STM image of MHO adlayer shows a
      modulation in intensity, reflecting the presence of various conformations of
      adsorbed molecules. This result is attributed to the shorter chain length of MHO,
      which gives a weaker van der Waals interaction between adsorbed molecules. This
      effect also results in a higher charge permeability across the adlayer and a
      lower striping potential to an MHO SAM.

PMID- 21730708
TI  - Submolecular resolution viscoelastic imaging of a poly(p-toluene-sulfonate)
      single crystal using force modulation microscopy.
AB  - Submolecular resolution viscoelastic imaging of a poly(2,4-hexadiyne-1,6-diyl
      bis(p-toluene-sulfonate)) single crystal was achieved using force modulation
      microscopy under ambient conditions. The elastic image clearly visualized the
      structure of p-toluene-sulfonate side chains. The viscotic image visualized that
      the phase delay on the main chains was smallest, while it became largest on the
      toluene rings in the side chains. The result is considered to be closely related
      to the molecular dynamics of the crystal.

PMID- 21730709
TI  - Computational modeling of the thermal conductivity of single-walled carbon
      nanotube-polymer composites.
AB  - A computational model was developed to study the thermal conductivity of single
      walled carbon nanotube (SWNT)-polymer composites. A random walk simulation was
      used to model the effect of interfacial resistance on the heat flow in different
      orientations of SWNTs dispersed in the polymers. The simulation is a modification
      of a previous model taking into account the numerically determined thermal
      equilibrium factor between the SWNTs and the composite matrix material. The
      simulation results agreed well with reported experimental data for epoxy and
      polymethyl methacrylate (PMMA) composites. The effects of the SWNT orientation,
      weight fraction and thermal boundary resistance on the effective conductivity of
      composites were quantified. The present model is a useful tool for the prediction
      of the thermal conductivity within a wide range of volume fractions of the SWNTs,
      so long as the SWNTs are not in contact with each other. The developed model can
      be applied to other polymers and solid materials, possibly even metals.

PMID- 21730710
TI  - The effect of two neighboring defects on the mechanical properties of carbon
      nanotubes.
AB  - The tensile behavior of single-walled nanotubes (SWNTs) having two defects
      (vacancy or Stone-Wales) positioned next to each other was simulated in this
      study to investigate the influence of the spatial arrangement of defects on the
      mechanical properties. The simulations were performed using classical molecular
      dynamics (MD) at the atomic scale. Two neighboring vacancy defects reduced the
      failure strength as much as 46% and the failure strain as much as 80% in
      comparison with those of pristine SWNTs, while two neighboring Stone-Wales
      defects reduced them as much as 34% and 70% respectively. SWNTs having two
      defects in the loading (axial) direction showed higher failure strength than
      SWNTs with defects perpendicular to the loading direction. For both types of
      defect, the closer the defects, the weaker the SWNTs. As result, the defect
      arrangement in the SWNT structure must be one of the key factors in determining
      its mechanical properties, as well as the population of defects.

PMID- 21730711
TI  - Direct growth and photoelectrochemical properties of tungsten oxide nanobelt
      arrays.
AB  - A single-step route was developed for the direct growth of tungsten oxide
      nanobelt arrays by heating a tungsten sheet without additional catalysts or
      reactants. X-ray diffraction and Raman analysis indicated that the tungsten oxide
      nanobelts were monoclinic. The surface photovoltage signal and photocurrent
      density of the tungsten oxide nanobelt arrays clearly suggested a high
      photoconversion ability. Further investigation demonstrated that the
      photoelectrocatalytic activity of the nanobelt arrays was higher than that of a
      tungsten oxide film when using phenol as the probe molecule.

PMID- 21730712
TI  - Coating of meso-porous metallic membranes with oriented channel-like fine pores
      by pulsed laser deposition.
AB  - There is increasing demand to functionalize meso- and nanoporous materials by
      coating and make the porous substrate biocompatible or environmentally friendly.
      However, coating on a meso-porous substrate poses great challenges, especially if
      the pore aspect ratio is high. We adopted the pulsed laser deposition (PLD)
      method to coat Ni(3)Al-based meso-porous membranes, which were fabricated from a
      single-crystal Ni-based superalloy by a unique selective phase dissolution
      technique. These membranes were about 250 um thick and had channel-like pores
      (~200 nm wide) with very high aspect ratio. Two different coating materials, i.e.
      diamond-like carbon (DLC) and titanium, were used to coat these membranes. High
      energy C or Ti ions, produced in the plasma plume by the PLD process, penetrated
      the channel-like pores and deposited coatings on the pore walls deep inside the
      membrane. The thickness and the quality of coatings on the pore walls were
      examined using the dual-beam system. The coating thickness, of the order of 50
      nm, was adherent to the pore walls and was quite uniform at different depths. The
      carbon and the Ti deposition behaved quite similarly. The preliminary experiments
      showed that the PLD is an adequate method for coating fine open cavities of
      complex geometry. Simulations based on stopping and the range of ions in matter
      (SRIM) calculations helped in understanding the deposition processes on pore
      walls at great depths.

PMID- 21730713
TI  - Biopolymer/montmorillonite nanocomposite: preparation, drug-controlled release
      property and cytotoxicity.
AB  - In order to combine the advantages of a biopolymer with clay in a drug delivery
      system, the hot intercalation technique was used to prepare quaternized
      chitosan/montmorillonite (HTCC/MMT) nanocomposites. Transmission electron
      microscopy (TEM), x-ray diffraction (XRD) and Fourier transform infrared
      spectroscopy (FT-IR) results revealed that HTCC chains entered into the
      interlayer of MMT, and the interaction between them has taken place. This is the
      basis of the advantage combination. Then the HTCC/MMT nanocomposites were
      modified to prepare the nanoparticles, whose drug-controlled release behaviours
      were evaluated. The results suggested that, compared to pure HTCC nanoparticles,
      certain montmorillonite loadings on quaternized chitosan enhanced the drug
      encapsulation efficiency of the nanoparticles and slowed the drug release from
      the nanocomposites. Finally, a study of 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyl tetrazolium bromide (MTT) indicated that the nanocomposites are not
      cytotoxic. Therefore, the HTCC/MMT nanocomposites are of great potential in the
      biomedical field.

PMID- 21730714
TI  - A model calculation of the tip field distribution for a carbon nanotube array and
      the optimum intertube distance.
AB  - In a previous paper, the model of a floating top segment was proposed and used
      successfully to calculate the field enhancement factor as well as the field
      distribution on the top surface for a single carbon nanotube (CNT). In this
      paper, the model is extended to a CNT array. A set of modified linear charge
      equations has been derived for the CNT array using an approximation of multipole
      potential expansion. Fictitious charges inside a specific segment can be solved
      from these equations to calculate the field around the tips. Some numerical
      calculations of the field enhancement factor have been carried out,
      quantitatively accounting for the reduction of the factor with decreasing
      intertube distance. The relative field strength distribution on the top
      hemisphere of a CNT array is calculated too; it is observed to be close to that
      of a single CNT. Using the Fowler-Nordheim formula, the field emission intensity
      of a CNT array is maximized with varying intertube distance. The resulting
      optimum intertube distance to height ratio decreases gradually with increasing
      height to radius ratio, and is close to 2 only for height to radius ratio around
      3 * 10(2).

PMID- 21730715
TI  - Surface potential domains on lamellar P3OT structures.
AB  - In this work the electrostatic properties of poly(3-octylthiophene) thin films
      have been studied on a nanometer scale by means of electrostatic force microscopy
      and Kelvin probe microscopy (KPM). The KPM images reveal that different surface
      contact potential domains coexist on the polymer surface. This result, together
      with additional capacitance measurements, indicates that the potential domains
      are related to the existence of dipoles due to different molecular arrangements.
      Finally, capacitance measurements as a function of the tip-sample bias voltage
      show that in all regions large band bending effects take place.

PMID- 21730716
TI  - Synthesis and field electron emission properties of hybrid carbon nanotubes and
      nanoparticles.
AB  - Hybrid ZnO-carbon nanotubes as well as nanodiamond-carbon nanotubes were
      synthesized via a straightforward process of plasma enhanced chemical vapor
      deposition. For the former, ZnO nanoparticles were instantly coated on the tube
      surface in the final growing process of carbon nanotubes, while for the latter
      diamond nanoparticles were grown using pretreatment of a silicon substrate with
      Ni(NO(3))(2).6H(2)O/Mg(NO(3))(2).6H(2)O alcohol solution prior to deposition and
      a high H(2)/CH(4) gas flow ratio in the deposition process. The morphology and
      microstructure of the obtained hybrid materials were characterized by
      transmission electron microscopy. Both hybrid ZnO-carbon nanotubes and
      nanodiamond-carbon nanotubes exhibited excellent field emission properties.

PMID- 21730717
TI  - Characterization of silver nanoparticles synthesized on titanium dioxide fine
      particles.
AB  - Silver nanoparticles with a narrow size distribution were synthesized over the
      surface of two different commercial TiO(2) particles using a simple aqueous
      reduction method. The reducing agent used was NaBH(4); different molar ratios
      TiO(2):Ag were also used. The nanocomposites thus prepared were characterized
      using transmission electron microscopy (TEM), scanning transmission electron
      microscopy (STEM), scanning electron microscopy (SEM), energy-dispersive
      spectroscopy (EDS), x-ray photoelectron spectroscopy (XPS), x-ray diffraction
      (XRD), dynamic light scattering (DLS) and UV-visible (UV-vis) absorption
      spectroscopy; the antibacterial activity was assessed using the standard
      microdilution method, determining the minimum inhibitory concentration (MIC)
      according to the National Committee for Clinical Laboratory Standards. From the
      microscopy studies (TEM and STEM) we observed that the silver nanoparticles are
      homogeneously distributed over the surface of TiO(2) particles and that the
      TiO(2):Ag molar ratio plays an important role. We used three different TiO(2)Ag
      molar ratios and the size of the silver nanoparticles is 10, 20 and 80 nm,
      respectively. It was found that the antibacterial activity of the nanocomposites
      increases considerably comparing with separated silver nanoparticles and TiO(2)
      particles.

PMID- 21730718
TI  - Magnetoresistance of oblique angle deposited multilayered Co/Cu nanocolumns
      measured by a scanning tunnelling microscope.
AB  - In this work we present the first magnetoresistance measurements on multilayered
      vertical Co(~6 nm)/Cu(~6 nm) and slanted Co(x nm)/Cu(x nm) (with x~6, 11, and 16
      nm) nanocolumns grown by oblique angle vapour deposition. The measurements are
      performed at room temperature on the as-deposited nanocolumn samples using a
      scanning tunnelling microscope to establish electronic contact with a small
      number of nanocolumns while an electromagnet generates a time varying (0.1 Hz)
      magnetic field in the plane of the substrate. The samples show a giant
      magnetoresistance (GMR) response ranging from 0.2 to 2%, with the higher GMR
      values observed for the thinner layers. For the slanted nanocolumns, we observed
      anisotropy in the GMR with respect to the relative orientation (parallel or
      perpendicular) between the incident vapour flux and the magnetic field applied in
      the substrate plane. We explain the anisotropy by noting that the column axis is
      the magnetic easy axis, so the magnetization reversal occurs more easily when the
      magnetic field is applied along the incident flux direction (i.e., nearly along
      the column axis) than when the field is applied perpendicular to the incident
      flux direction.

PMID- 21730719
TI  - Magnetic field enhanced nano-tip fabrication for four-probe STM studies.
AB  - We present an improved method for fabricating tungsten STM tips for measuring
      nanoscale objects using a multiprobe STM. The tips were prepared by a 'drop-off'
      technique combined with a magnetic field. For magnetic field strengths above 150
      Oe the electrolyte was seen to rotate about the tungsten anode. This rotation
      reduced the adhesion of bubbles and led to a reduction in the cone angle of the
      tips produced. This property is advantageous for multiprobe measurements as it
      allows one to bring multiple tips into close proximity.

PMID- 21730720
TI  - The effects of contacts and ambipolar electrical transport in nitrogen doped
      multiwall carbon nanotubes.
AB  - The electrical transport properties of pristine single wall carbon nanotubes
      (SWCNTs) and lower nitrogen content doped multiwall carbon nanotubes (MWCNTs)
      (lower than in the experiments of Xiao et al (2005 J. Am. Chem. Soc. 127 8614))
      in contact with Au and Pt were studied. Compared with pristine SWCNTs, the Fermi
      level of the lower nitrogen content doped MWCNTs also moved to the valence band
      edge with the contact metal's work function increasing. In contrast to Derycke et
      al' s results (2002 Appl. Phys. Lett. 80 2773), the lower nitrogen content doped
      MWCNTs exhibited ambipolar behavior, and increasing the doping level led to a
      reduction of the Schottky barrier height of electrons. Consistent with
      theoretical calculations, the results support the opinion that the degree of
      Fermi level pinning is minor for doped carbon nanotubes.

PMID- 21730721
TI  - Semiconductor quantum templates: bottom-up design of optical devices and photonic
      circuits using sub-nanoscale high monolayer features and quantum optics.
AB  - We propose an alternative bottom-up technique for designing, fabricating and
      monolithically integrating optical components, including functional distributed
      feedback lasers, modulators, waveguides, etc in a single semiconductor wafer
      without any need for etching or post-processing epitaxial growth. The proposed
      technique is based on the formation of semiconductor quantum templates at the
      well/barrier interfaces of quantum well structures. Such templates are
      responsible for changing the thickness of a quantum well in designated regions by
      adding one extra monolayer of the well material in those regions during the
      growth process. We show that, using a control laser field, these templates or sub
      nanoscale high monolayer features allow us to spatially control the formation of
      electromagnetically induced transparency, gain without inversion, and coherent
      enhancement/suppression of the refractive index along the plane of the quantum
      well. We demonstrate that this can lead to bottom-up design capabilities for
      functional optical devices and their monolithic integration using a single
      epitaxial growth process.

PMID- 21730722
TI  - Surface patterning for brittle amorphous material using nanoindenter-based
      mechanochemical nanofabrication.
AB  - This paper demonstrates a micro/nanoscale surface patterning technology for
      brittle material using mechanical and chemical processes. Fused silica was
      scratched with a Berkovich tip under various normal loads from several mN to
      several tens of mN with various tip rotations. The scratched substrate was then
      chemically etched in hydrofluoric solution to evaluate the chemical properties of
      the different deformed layers produced under various mechanical scratching
      conditions. Our results showed that either protruding or depressed patterns could
      be generated on the scratched surface after chemical etching by controlling the
      tip rotation, the normal load and the etching condition. In addition, the mask
      effect of amorphous material after mechanical scratching was controlled by
      conventional mechanical machining conditions such as contact area, chip
      formation, plastic flow and material removal.

PMID- 21730723
TI  - Magnetoresistance behavior of ferromagnetic nanorings in a ring-wire hybrid
      configuration.
AB  - We present a technique for probing the magnetic configurations in ferromagnetic
      rings electrically without placing the electrical contact leads directly on the
      nanorings, but on wires attached to the ring structures. The magnetic
      configurations in pseudo spin valve rectangular and elliptical rings of width in
      the range from 60 to 300 nm have been systematically mapped using this technique.
      The giant magnetoresistance (GMR) responses for both the rings exhibit distinct
      switching fields and features corresponding to identifiable magnetization states
      in different segments of the nanostructures.

PMID- 21730724
TI  - Wafer-level assembly of carbon nanotube networks using dielectrophoresis.
AB  - We use dielectrophoresis (DEP) to controllably and simultaneously assemble
      multiple carbon nanotube (CNT) networks at the wafer level. By an appropriate
      choice of electrode dimensions and geometry, an electric field is generated that
      captures CNTs from a sizable volume of suspension, resulting in good CNT network
      uniformity and alignment. During the DEP process, the electrical characteristics
      of the CNT network are measured and correlated with the network morphology. These
      experiments give novel insight into the physics of DEP assembly of CNT networks,
      and demonstrate the scalability of DEP for future device applications.

PMID- 21730725
TI  - Synthesis and characterization of monodisperse ultra-thin silica-coated magnetic
      nanoparticles.
AB  - A systematic study of the formation of silica-coated magnetite particles via a
      modified reverse microemulsion approach was investigated by using transmission
      electron microscopy (TEM), x-ray diffraction (XRD) and a superconducting quantum
      interference device (SQUID). The results show that the surfactant Igepal CO-520
      played an important role in the reaction system, and the thickness of the silica
      shell could be controlled by the concentration of the reaction agents. The
      developed ultra-thin silica-coated magnetic particles with a ~2 nm thin silica
      shell have a high saturated magnetization around 15 emu g(-1).

PMID- 21730726
TI  - Synthesis of mercaptothiadiazole-functionalized gold nanoparticles and their self
      assembly on Au substrates.
AB  - Gold nanoparticles (AuNPs) stabilized with mercaptothiadiazole ligands, 2,5
      dimercapto-1,3,4-thiadiazole (DMT), 5-amino-2-mercapto-1,3,4-thiadiazole (AMT)
      and 5-methyl-2-mercapto-1,3,4-thiadiazole (MMT), were prepared by the reaction of
      the respective ligands with HAuCl(4) and NaBH(4) in an aqueous medium. TEM images
      show that the average size of AuNPs was 6.5 +/- 0.5 nm, irrespective of the
      capping ligands. The colloidal solution of both DMT-capped AuNPs (DMT-AuNPs) and
      AMT-capped AuNPs (AMT-AuNPs) were highly stable for several months. However,
      several changes were noticed for MMT-capped AuNPs (MMT-AuNPs) after 2 h from its
      formation. The SPR band intensity at 518 nm decreases and the narrow SPR
      absorption band slowly changes into a flat absorption pattern with a broad peak
      from 518 to 1000 nm which was accompanied by a colour change of the solution from
      red to purple and then blue and thereafter unchanged. The TEM image of MMT-AuNPs
      after 96 h shows that most of the spherical shape of the AuNPs assembled to form
      a nanowire-like structure. The observed changes may be due to the absence of a
      strong stabilizing force on the surface of the MMT-AuNPs. The amino and thiolate
      groups on the surface of the AMT-AuNPs and DMT-AuNPs, respectively, were directly
      self-assembled on Au electrodes. They exhibit excellent electrocatalytic activity
      towards the oxidation of AA by enhancing its oxidation current twice in addition
      to more than 200 mV negative shift in the oxidation potential in contrast to bare
      Au electrode.

PMID- 21730727
TI  - First-step nucleation growth dependence of InAs/InGaAs/InP quantum dot formation
      in two-step growth.
AB  - First-step nucleation growth has an important impact on the two-step growth of
      high-quality mid-infrared emissive InAs/InGaAs/InP quantum dots (QDs). It has
      been found that an optimized growth rate for first-step nucleation is critical
      for forming QDs with narrow size distribution, high dot density and high crystal
      quality. High growth temperature has an advantage in removing defects in the QDs
      formed, but the dot density will be reduced. Contrasting behavior in forming InAs
      QDs using metal-organic vapor phase epitaxy (MOVPE) by varying the input flux
      ratio of group-V versus group-III source (V/III ratio) in the first-step
      nucleation growth has been observed and investigated. High-density, 2.5 * 10(10)
      cm(-2), InAs QDs emitting at>2.15 um have been formed with narrow size
      distribution, ~1 nm standard deviation, by reducing the V/III ratio to zero in
      first-step nucleation growth.

PMID- 21730728
TI  - Diameter control of tungsten oxide nanowires as grown by thermal evaporation.
AB  - Tungsten oxide nanowires with controllable diameter were synthesized on Si
      substrates by thermal evaporation of tungsten trioxide powder in a tube furnace.
      Depending on the temperature of the source (900-1000  degrees C), tungsten oxide
      W(18)O(49) nanowires with diameters ranging from 10 to 100 nm are obtained with
      high yield. The exponential dependence of the nanowire diameter on the source
      temperature leads to an energy of about 2.0 eV. The growth process is discussed;
      it is believed to be a kinetic effect.

PMID- 21730729
TI  - Preparation and characterization of silica nanoparticulate-polyacrylonitrile
      composite and porous nanofibers.
AB  - In this study, polyacrylonitrile (PAN) composite nanofibers containing different
      amounts of silica nanoparticulates have been obtained via electrospinning. The
      surface morphology, thermal properties and crystal structure of PAN/silica
      nanofibers are characterized using attenuated total reflection Fourier transform
      infrared (ATR-FTIR) spectroscopy, wide-angle x-ray diffraction (WAXD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), and
      differential scanning calorimetry (DSC). The results indicate that the addition
      of silica nanoparticulates affects the structure and properties of the
      nanofibers. In addition to PAN/silica composite nanofibers, porous PAN nanofibers
      have been prepared by selective removal of the silica component from PAN/silica
      composite nanofibers using hydrofluoric (HF) acid. ATR-FTIR and thermal
      gravimetric analysis (TGA) experiments validate the removal of silica
      nanoparticulates by HF acid, whereas SEM and TEM results reveal that the porous
      nanofibers obtained from composite fibers with higher silica contents exhibited
      more nonuniform surface morphology. The Brunauer-Emmett-Teller (BET) surface area
      of porous PAN nanofibers made from PAN/silica (5 wt%) composite precursors is
      higher than that of pure nonporous PAN nanofibers.

PMID- 21730730
TI  - Direct synthesis of ultralong carbon nanotube bundles by spray pyrolysis and
      investigation of growth mechanism.
AB  - A mass of ultralong aligned carbon nanotube (CNT) bundles up to about 8 mm in
      length was synthesized by utilizing the spray pyrolysis of ferrocene/xylene
      solutions in the absence of promoters, such as thiophene or pure sulfur, and
      etching agents, such as plasma, oxygen, ethanol or water. Scanning electron
      microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM)
      results indicated the continuous and multi-walled nanotube structure for the CNTs
      in the macroscopical bundles. A graph demonstrating the correlation between
      growth time and length of CNT arrays revealed that the maximum growth rate
      reaches approximately 4612 nm s(-1). Based on the experimental phenomena and
      results, a continuous rapid growth mechanism in both directions was proposed,
      which suggests that longer CNT arrays can be synthesized at this rapid growth
      rate if the growth time is extended.

PMID- 21730731
TI  - Synthesis and characterization of ZnO/MgZnO heterostructure nanorods by simple
      two-step evaporation.
AB  - ZnO-core/MgZnO-shell heterostructure nanorods with high aspect ratio were
      synthesized using a two-step thermal evaporation procedure, in which the core and
      the shell layers were formed separately at different temperatures.
      Microstructural characterization revealed a position dependence of the crystal
      structure and composition in the shell layer. The shell layer in the upper region
      consisted of MgO with quantum dot-like structure having cubic phases embedded in
      an amorphous oxide layer, while a Mg(0.35)Zn(0.65)O shell layer with a self
      assembled superlattice structure of triple periodicity was formed in the middle
      region.

PMID- 21730732
TI  - FePt and CoPt nanoparticles co-deposited on silicon dioxide-a comparative study.
AB  - We compare CoPt and FePt nanoparticles grown under identical conditions on
      oxidized Si substrates by electron beam co-evaporation. Growth was performed
      under high vacuum conditions at substrate temperatures of 1023 K and was
      immediately followed by an annealing step. This process forms CoPt and FePt
      nanoparticles with mean diameters between ~17 and ~22 nm. In particular, the
      annealing step results in grain size enlargement for all samples and in a
      progressive magnetic hardening of the nanoparticles which reach maximum
      perpendicular coercivities of ~6.6 kOe (for the CoPt) and ~10.2 kOe (for the FePt
      nanoparticles). We show that, during this annealing step, a progressive
      transition towards the hard magnetic L1(0) ordered phase takes place in both
      materials. In contrast to FePt, CoPt nanoparticles must be annealed in order to
      crystallize in this phase.

PMID- 21730733
TI  - Vibrational analysis of single-layered graphene sheets.
AB  - A molecular structural mechanics method has been implemented to investigate the
      vibrational behavior of single-layered graphene sheets. By adopting this
      approach, mode shapes and natural frequencies are obtained. Vibrational analysis
      is performed with different chirality and boundary conditions. Numerical results
      from the atomistic modeling are employed to develop predictive equations via a
      statistical nonlinear regression model. With the proposed equations, fundamental
      frequencies of single-layered graphene sheets with considered boundary conditions
      can be predicted within 3% difference with respect to the atomistic simulation.

PMID- 21730734
TI  - The prominent photoinduced voltage effect of as-prepared macroscopically long Ag
      core/Ni shell nanoheterojunctions.
AB  - Macroscopically long Ag core/Ni shell nanoheterojunctions have been well prepared
      by a dynamic growth approach. The structure characterized in detail by scanning
      electron microscopy reveals that the Ag nanowire bundles are wrapped in Ni
      nanoshields and form multicore coaxial cable frames. Notable photoinduced voltage
      with a fine repeatability, for irradiation with a laser, is exhibited compared
      with the case for bulk Ag pole/Ni shell heterojunctions and Ag nanowire
      bundle/bulk Ni heterojunctions. The prominent photoinduced voltage and the
      substantial metal nanoscale Ohmic interconnects provided by this kind of
      nanoheterojunction may have a wide range of applications in the future.

PMID- 21730735
TI  - Quantitative mechanical characterization of materials at the nanoscale through
      direct measurement of time-resolved tip-sample interaction forces.
AB  - We introduce a new method for material characterization at the nanoscale using a
      recently developed atomic force microscope (AFM) probe. The FIRAT (force sensing
      integrated readout and active tip) probe is integrated into a commercial AFM
      system to obtain time-resolved interaction forces (TRIFs) between the probe tip
      and sample at speeds suitable for nondestructive and fast imaging of material
      properties. We present a basic interaction model to extract the material
      elasticity and surface energy. Numerical simulations are performed and compared
      to the experimental results for three different polymers and a silicon sample. We
      find that our interaction model does not completely explain the observed long
      range surface forces, but it agrees fairly well with the measurements during the
      tip-sample contact.

PMID- 21730736
TI  - Preparation of iron boride-silica core-shell nanoparticles with soft
      ferromagnetic properties.
AB  - A one-pot aqueous chemical synthesis for silica-passivated ferromagnetic
      nanoparticles is presented. The average size of these particles is 84 +/- 20 nm.
      The x-ray and electron diffraction experiments revealed that the nanoparticles
      are mainly composed of polycrystalline iron boride. The broad x-ray diffraction
      peak leads to an average crystallite size of 1.8 nm, which is much smaller than
      the overall size of the particles, and is consistent with the polycrystalline
      nature of the samples. Mossbauer spectroscopy and magnetization experiments were
      used to establish the room temperature magnetic properties as well as the
      chemical nature of the particles. Fe(2)B dominates the composition of the
      nanoparticles, having a hyperfine field broadly distributed in the 10-33 T range.
      Alpha iron, the second ferromagnetic material identified in the particles,
      amounts to 4.6% of the composition. Finally, a paramagnetic phase accounting for
      approximately 14.6% of the material of the particles was also detected. These
      nanoparticles contain a core with soft ferromagnetic properties surrounded by a
      passivating silica layer, and are suitable for magnetically targeted drug
      delivery and electromagnetic induction heating applications.

PMID- 21730737
TI  - Structure and 1/f noise of boron doped polymorphous silicon films.
AB  - The influence of structure variation on the 1/f noise of nanometric boron doped
      hydrogenated polymorphous silicon (pm-Si:H) films was investigated. The films
      were grown by the conventional radio frequency plasma enhanced chemical vapor
      deposition (PECVD) method. Raman spectroscopy was used to reveal the crystalline
      volume fraction (X(c)) and crystal size of the pm-Si:H. The measurement of
      optical and structure properties was carried out with spectroscopic ellipsometry
      (SE) in the Tauc-Lorentz model. A Fourier transform infrared (FTIR) spectrometer
      was used to characterize the presence of nanostructure-sized silicon clusters in
      pm-Si:H film deposited on KBr substrate. The electrical properties of the films
      were measured using evaporated coplanar nickel as the electrode. A semiconductor
      system was designed to obtain the 1/f noise of pm-Si:H film as well as that of
      amorphous and microcrystalline silicon films. The results demonstrate that the
      1/f noise of pm-Si:H is nearly as low as that of microcrystalline silicon and
      much lower than that of amorphous silicon. The disorder to order transition
      mechanism of crystallization was used to analyze the decrease of noise compared
      with amorphous silicon.

PMID- 21730738
TI  - Preparation, characterization and antibacterial properties against E. coli K(88)
      of chitosan nanoparticle loaded copper ions.
AB  - The present study was conducted to prepare and characterize chitosan nanoparticle
      loaded copper ions, and evaluate their antibacterial activity. Chitosan
      nanoparticles were prepared based on ionotropic gelation, and then the copper
      ions were loaded. The particle size, zeta potential and morphology were
      determined. Antibacterial activity was evaluated against E. coli K(88) by
      determination of the minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) in vitro. Results showed that the antibacterial
      activity was significantly enhanced by the loading of copper ions compared to
      those of chitosan nanoparticles and copper ions. The MIC and MBC of chitosan
      nanoparticle loaded copper ions were 21 times and 42 times lower than those of
      copper ions, respectively. To confirm the antibacterial mechanism, morphological
      changes of E. coli K(88) treated by chitosan nanoparticle loaded copper ions were
      dynamically observed with an atomic force microscope (AFM). It was found that
      chitosan nanoparticle loaded copper ions killed E. coli K(88) through damage to
      the cell membrane.

PMID- 21730739
TI  - Developing nanoscale inertial measurement systems with carbon nanotube
      oscillators.
AB  - We have developed a conceptual design for an inertial measurement system using
      the oscillatory characteristics of carbon nanotube (CNT) oscillators with or
      without fillings, and performed molecular dynamics (MD) simulations to
      investigate its dynamic operations. In the operations, the instantaneous
      equilibrium position, which is uniquely related to the rotation, is traced by
      monitoring the variations of the tip-surface capacitance, i.e., the capacitance
      between a spherical cap of the oscillating CNT and an adjacent metallic plate.
      The MD simulations for the three model systems: the (5, 5)&(10, 10) CNT system,
      and the (10, 10)&(15, 15) CNT system with copper and gold fillings, respectively,
      show that the induced variations of the tip-surface capacitance can be
      significantly enhanced by increasing the size and the weight of the oscillating
      core of such an inertial measurement system.

PMID- 21730740
TI  - Observation of superconductivity in single crystalline Bi nanowires.
AB  - Bi nanowires have been fabricated by electrochemical deposition into the pores of
      ion track etched polycarbonate membranes. Transmission electron microscopy and
      selected area electron diffraction measurements reveal that these Bi nanowires
      are single crystalline with the rhombohedral lattice structure of bulk Bi at
      ambient pressure. We have measured the temperature dependence of the resistance
      and I-V characteristics at various magnetic fields on these Bi nanowires. These
      measurements show clear evidence for superconductivity below 0.64 K.

PMID- 21730741
TI  - Reinforcing polymer composites with epoxide-grafted carbon nanotubes.
AB  - An in situ functionalization method was used to graft epoxide onto single-walled
      carbon nanotubes (SWNTs) and improve the integration of SWNTs into epoxy polymer.
      The characterization results of Raman, FT-IR and transmission electron microscopy
      (TEM) validated the successful functionalization with epoxide. These
      functionalized SWNTs were used to fabricate nanocomposites, resulting in uniform
      dispersion and strong interfacial bonding. The mechanical test demonstrated that,
      with only 1 wt% loading of functionalized SWNTs, the tensile strength of
      nanocomposites was improved by 40%, and Young's modulus by 60%.These results
      suggested that efficient load transfer has been achieved through epoxide
      grafting. This investigation provided an efficient way to improve the interfacial
      bonding of multifunctional high-performance nanocomposites for lightweight
      structure material applications.

PMID- 21730742
TI  - In situ electrical measurements of polytypic silver nanowires.
AB  - Novel 4H structure silver nanowires (4H-AgNWs) have been reported to coexist with
      the usual face-centered cubic (FCC) ones. Here we report the electrical
      properties of these polytypic AgNWs for the first time. AgNWs with either 4H or
      FCC structures in the diameter range of 20-80 nm were measured in situ inside a
      transmission electron microscope (TEM). Both kinds of AgNW in the diameter range
      show metallic conductance. The average resistivity of the 4H-AgNWs is 19.9
      MUOmega cm, comparable to the 11.9 MUOmega cm of the FCC-AgNWs. The failure
      current density can be up to ~10(8) A cm(-2) for both 4H-and FCC-AgNWs. The
      maximum stable current density (MSCD) is introduced to estimate the AgNWs'
      current-carrying ability, which shows diameter-dependence with a peak around 34
      nm in diameter. It is attributed to fast annihilation of the current-induced
      vacancies and the enhanced surface scattering. Our investigations also suggest
      that the magnetic field of the electromagnetic lens may also introduce some
      influence on the measurements inside the TEM.

PMID- 21730743
TI  - A novel polymer nanotube composite for photovoltaic packaging applications.
AB  - Packaging of organic photovoltaic (OPV) devices is an important issue which has
      been rarely addressed in the past. With the recent reports of high efficiency
      organic photovoltaics (6%), the need to produce materials which can effectively
      protect the device from degradation due to exposure to oxygen, moisture and
      radiation is pressing. We report a novel Saran (a co-polymer of vinylidene
      chloride and acrylonitrile) based polymer nanotube composite, which shows high
      transparency in the visible region, good barrier properties and thermal
      stability, for use as an encapsulant for OPV devices. Different loadings of Saran
      and boron nitride nanotubes were taken and the composites were prepared to
      optimize the composition of the composite. UV-visible spectroscopy, infra-red
      spectroscopy and thermal analysis were used to characterize the composite. The
      barrier properties of the composite were tested on poly(3-hexylthiophene), which
      is used in high efficiency OPV devices.

PMID- 21730744
TI  - Modifying the surface charge of single track-etched conical nanopores in
      polyimide.
AB  - Chemical modification of nanopore surfaces is of great interest as it means that
      the surface composition is no longer fixed by the choice of substrate material,
      even to the point where large biomolecules can be attached to the pore walls.
      Controlling nanopore transport characteristics is one important application of
      surface modification which is very relevant given the significant interest in
      sensors based on the transport of ions and molecules through nanopores. Reported
      here is a method to change the surface charge polarity of single track-etched
      conical nanopores in polyimide, which also has the potential to attach more
      complex molecules to the carboxyl groups on the nanopore walls. These carboxyl
      groups were converted into terminal amino groups, first by activation with N-(3
      dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS)
      followed by the covalent coupling of ethylenediamine. This results in a changed
      surface charge polarity. Regeneration of a carboxyl-terminated surface was also
      possible, by reaction of the amino groups with succinic anhydride. The success of
      these reactions was confirmed by measurements of the pore's pH sensitive current
      voltage (I-V) characteristics before and after the chemical modification, which
      depend on surface charge. The permselectivity of the pores also changed
      accordingly with the modification.

PMID- 21730745
TI  - Thermo-magnetic recording on a Co/Pt perpendicular film by a sharp metallic
      probe.
AB  - We studied a method of heat-assisted magnetic recording (HAMR). The recording
      medium is a strongly coupled Co/Pt multilayered thin film, suitable for
      perpendicular recording. Field emission current from a scanning tunneling
      microscope (STM) tip is used as the heating source. Pulse voltages of 5 V were
      applied to the film. Experimental results show that an average mark size of 100
      120 nm was achieved, with the minimum being 45 nm. Models of domain stability and
      dynamic domain formation are built to quantitatively explain the experimental
      results. They agree well with experiments. The models give us future directions
      for achieving small marks for ultra-high recording density.

PMID- 21730746
TI  - Small-angle neutron scattering measurement of silicon nanoparticle size.
AB  - We have determined the particle size distribution profiles of octane-terminated
      silicon nanoparticle suspensions, produced using the sonication of
      electrochemically etched Si wafers. Small-angle neutron scattering data was
      analyzed separately in high (0.4 nm(-1)<q<3.0 nm(-1)) and low (q<0.4 nm(-1))
      scattering vector ranges. Data in the high q range is consistent with the log
      normal distribution of isolated spherical particles with median diameter d = 3 +/
      0.2 nm. Particle sizes were also indirectly assessed from photoluminescence and
      optical transmission spectroscopy using the size/bandgap relation: E(g) = 3.44d(
      0.5), where E(g) is in eV and d in nm. Both measurements were consistent with the
      particle size distribution profiles, estimated from ANS data fitting and TEM
      image analysis. A subpopulation of larger, irregular shape structures in the size
      range 10-50 nm was also indicated by neutron scattering in the low q range and
      HRTEM images. However, further studies are warranted to explain a relationship
      between the slope of scattering intensity versus scattering vector dependence in
      the intermediate scattering vector range (0.4 nm(-1)<q<1.0 nm(-1)) and the role
      of non-geometrical Si nanoparticle characteristics (mutual interaction forces,
      surface termination, etc).

PMID- 21730747
TI  - Synthesis and electrochemical probing of water-soluble poly(sodium 4
      styrenesulfonate-co-acrylic acid)-grafted multiwalled carbon nanotubes.
AB  - Water-soluble poly(sodium 4-styrenesulfonate-co-acrylic acid)-grafted multiwalled
      carbon nanotubes (MWNT-g-P(SSS-co-AA)) with core-shell nanostructure were
      successfully synthesized by in situ free radical copolymerization of sodium 4
      strenesulfonate (SSS) and acrylic acid (AA) in the presence of MWNTs terminated
      with vinyl groups; their structure was characterized by FTIR, (1)H NMR, Raman,
      TGA and TEM. The results showed that the thickness and content of the copolymer
      layer grafted onto the MWNT surface are about 7-12 nm and 82.3%, respectively.
      The P(SSS-co-AA) covalently grafted on MWNTs provides MWNT-g-P(SSS-co-AA) with
      good hydrophilicity and solubility in water. Then a novel MWNT-g-P(SSS-co-AA)
      modified glassy carbon electrode was fabricated by coating; its electrochemical
      properties were evaluated by electrochemical probe of K(3)[Fe(CN)(6)], and its
      catalytic behaviors to the electrochemical oxidation processes of dopamine (DA)
      and serotonin (5-HT) were investigated. Since the MWNT-g-P(SSS-co-AA)-modified
      electrode possesses strong electron transfer capability, high electrochemical
      activity and catalytic ability, it can be used in sensitive, selective, rapid and
      simultaneous monitoring of biomolecules.

PMID- 21730748
TI  - Plasticity-modulated seizure dynamics for seizure termination in realistic
      neuronal models.
AB  - In previous studies we showed that autonomous absence seizure generation and
      termination can be explained by realistic neuronal models eliciting bi-stable
      dynamics. In these models epileptic seizures are triggered either by external
      stimuli (reflex epilepsies) or by internal fluctuations. This scenario predicts
      exponential distributions of the duration of the seizures and of the inter-ictal
      intervals. These predictions were validated in rat models of absence epilepsy, as
      well as in a few human cases. Nonetheless, deviations from the predictions with
      respect to seizure duration distributions remained unexplained. The objective of
      the present work is to implement a simple but realistic computational model of a
      neuronal network including synaptic plasticity and ionic current dynamics and to
      explore the dynamics of the model with special emphasis on the distributions of
      seizure and inter-ictal period durations. We use as a basis our lumped model of
      cortical neuronal circuits. Here we introduce 'activity dependent' parameters,
      namely post-synaptic voltage-dependent plasticity, as well as a voltage-dependent
      hyperpolarization-activated current driven by slow and fast activation
      conductances. We examine the distributions of the durations of the seizure-like
      model activity and the normal activity, described respectively by the limit cycle
      and the steady state in the dynamics. We use a parametric gamma-distribution fit
      as a quantifier. Our results show that autonomous, activity-dependent membrane
      processes can account for experimentally obtained statistical distributions of
      seizure durations, which were not explainable using the previous model. The
      activity-dependent membrane processes that display the strongest effect in
      accounting for these distributions are the hyperpolarization-dependent cationic
      (I(h)) current and the GABAa plastic dynamics. Plastic synapses (NMDA-type) in
      the interneuron population show only a minor effect. The inter-ictal statistics
      retain their consistency with the experimental data and the previous model.

PMID- 21730749
TI  - Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters
      astrocyte metabolism and dorsal root ganglia neurite outgrowth.
AB  - Following central nervous system (CNS) injury, activated astrocytes form a glial
      scar that inhibits the migration of axons ultimately leading to regeneration
      failure. Biomaterials developed for CNS repair can provide local delivery of
      therapeutics and/or guidance mechanisms to encourage cell migration into damaged
      regions of the brain or spinal cord. Electrospun fibers are a promising type of
      biomaterial for CNS injury since these fibers can direct cellular and axonal
      migration while slowly delivering therapy to the injury site. In this study, it
      was hypothesized that inclusion of an anti-metabolite, 6-aminonicotinamide (6AN),
      within poly-l-lactic acid electrospun fibers could attenuate astrocyte metabolic
      activity while still directing axonal outgrowth. Electrospinning parameters were
      varied to produce highly aligned electrospun fibers that contained 10% or 20%
      (w/w) 6AN. 6AN release from the fiber substrates occurred continuously over 2
      weeks. Astrocytes placed onto drug-releasing fibers were less active than those
      cultured on scaffolds without 6AN. Dorsal root ganglia placed onto control and
      drug-releasing scaffolds were able to direct neurites along the aligned fibers.
      However, neurite outgrowth was stunted by fibers that contained 20% 6AN. These
      results show that 6AN release from aligned, electrospun fibers can decrease
      astrocyte activity while still directing axonal outgrowth.

PMID- 21730750
TI  - Preparation of water-dispersible graphene by facile surface modification of
      graphite oxide.
AB  - Water-dispersible graphene was prepared by reacting graphite oxide and 6-amino-4
      hydroxy-2-naphthalenesulfonic acid (ANS). X-ray diffraction study showed that the
      basal reflection (002) peak of graphite oxide was absent in the ANS
      functionalized graphene (ANS-G), indicating crystal layer delamination.
      Ultraviolet-visible spectral data were recorded to assess the solubility of the
      ANS-G in water. Fourier transform infrared spectral analysis suggested the
      attachment of ANS molecules to the surface of graphene. Raman and x-ray
      photoelectron spectroscopy revealed that oxygen functionality in the graphite
      oxide had been removed during reduction. Atomic force microscopy found that the
      thickness of ANS-G in water was about 1.8 nm, much higher than that of single
      layer graphene. Thermal stability measurements also indicated successful removal
      of oxygen functionality from the graphite oxide and the attachment of thermally
      unstable ANS to the graphene surfaces. The electrical conductivity of ANS-G,
      determined by a four-point probe, was 145 S m(-1) at room temperature.

PMID- 21730751
TI  - Formation of thick dielectrophoretic carbon nanotube fibers.
AB  - The aim of this work was to study the formation process of dielectrophoretic
      (DEP) carbon nanotube fibers (CNT-fibers) and characterize the fiber properties
      relevant to their technological applications. The fiber diameter was shown to
      increase when applied voltage was increased (up to 350 V(pp)) and when retraction
      speed was decreased (down from 400 um s(-1)) in accordance with theoretical
      expectations. This paper represents the first demonstration of the formation of
      thick DEP CNT-fibers (up to ~ ?0.4 mm). This is an intriguing result, as it
      expands the diversity of possible applications of the fibers and facilitates
      their characterization by analytical methods that require large quantities of the
      material. The performance of these thick fibers was as follows: a density of ~
      0.35 g cm(-3), a tensile strength of ~ 15 MPa, a Young's modulus of ~ 1 GPa, and
      an electrical resistivity of ~ 70 mOmega cm.

PMID- 21730752
TI  - Shaping surface of palladium nanospheres through the control of reaction
      parameters.
AB  - Solid, cracked, and flower-shaped surfaces of palladium nanospheres with high
      yields and good uniformity were successfully prepared by a wet chemical method.
      On the basis of the experimental data, the same size of palladium nanosphere with
      different surface morphologies can be regulated only by changing the amount of
      ammonium hydroxide and reductant in one experimental system. The as-prepared
      products were studied by transmission electron microscopy (TEM), scanning
      electron microscopy (SEM) and x-ray diffraction (XRD). In addition, surface
      enhanced Raman scattering (SERS) spectra on the as-prepared different surface of
      palladium nanospheres exhibit high activity towards p-aminothiophenol (PATP)
      detection, and the result further reveals that the predominance of the a1
      vibration mode in the SERS spectra via an electromagnetic (EM) mechanism is
      significant.

PMID- 21730753
TI  - Synthesis and release of trace elements from hollow and porous hydroxyapatite
      spheres.
AB  - It is known that organic species regulate fabrication of hierarchical biological
      forms via solution methods. However, in this study, we observed that the presence
      of inorganic ions plays an important role in the formation and regulation of
      biological spherical hydroxyapatite formation. We present a mineralization method
      to prepare ion-doped hydroxyapatite spheres with a hierarchical structure that is
      free of organic surfactants and biological additives. Porous and hollow strontium
      doped hydroxyapatite spheres were synthesized via controlling the concentration
      of strontium ions in a calcium and phosphate buffer solution. Similarly, fluoride
      and silicon-doped hydroxyapatite spheres were synthesized. While spherical
      particle formation was attainable at low and high temperature for Sr-doped
      hydroxyapatite, it was only possible at high temperature in the F/Si-doped
      system. The presence of inorganic ions not only plays an important role in the
      formation and regulation of biological spherical hydroxyapatite, but also could
      introduce pharmaceutical effects as a result of trace element release. Such ion
      release results showed a sustained release with pH responsive behavior, and
      significantly influenced the hydroxyapatite re-precipitation. These ion-doped
      hydroxyapatite spheres with hollow and porous structure could have promising
      applications as bone/tooth materials, drug delivery systems, and chromatography
      supports.

PMID- 21730754
TI  - Palladium urchin-like nanostructures and their H2 sorption properties.
AB  - Urchin-like palladium nanostructures were synthesized by slow radiolytic
      reduction of Pd(II) in cetylpyridinium chloride (CPCl) micellar solution. They
      were formed by polycrystalline nanowires originating from the same core. The
      growth process leading to these urchin-like structures has been studied. These
      three-dimensional (3D) nanostructures were obtained at high Pd concentration (0.1
      M) which led to a relatively large quantity of nanomaterials. These
      nanostructures show very interesting cycling sorption properties for hydrogen
      storage.

PMID- 21730755
TI  - White emission by self-regulated growth of InGaN/GaN quantum wells on in situ
      self-organized faceted n-GaN islands.
AB  - The in situ self-organization of three-dimensional n-GaN islands of distinct
      sidewall faceting was realized by initial low V/III ratio growth under high
      reactor pressure followed by variations of the V/III ratio and reactor pressure.
      The naturally formed faceted islands with top and sidewall facets of various
      specific polar angles may serve as an ideal template for self-regulated growth of
      the InGaN/GaN multiple quantum wells (MQWs), i.e. the growth behavior is specific
      polar angle dependent. Further, the growth behavior and luminescence properties
      of the InGaN/GaN MQWs on various facets of different specific polar angles are
      directly compared and discussed. Tetrachromatic white emissions (blue, cyan,
      green, and red) from single-chip phosphor-free InGaN/GaN MQWs are realized by
      color tuning through island shaping, shape variations, and self-regulated growth
      of the InGaN/GaN MQWs.

PMID- 21730756
TI  - A study on the thermochemotherapy effect of nanosized As2O3/MZF thermosensitive
      magnetoliposomes on experimental hepatoma in vitro and in vivo.
AB  - In this paper, we describe the synthesis and characterization of a nanosized,
      thermosensitive magnetoliposome encapsulating magnetic nanoparticles (MZFs) and
      antitumor drugs (As(2)O(3)). The nanoliposomes were spherical and mostly single
      volume, with an average diameter of 128.2 nm. Differential scanning calorimetry
      (DSC) showed a liposome phase transition temperature of 42.71  degrees C. After
      that, we studied the liposomes' anti-hepatoma effect in vitro and in vivo. The
      antitumor effect of the nanoliposomes on human hepatoma cells, SMMC-7721, and
      changes in expression of apoptosis-related proteins were examined in vitro. The
      results show that As(2)O(3)/MZF thermosensitive magnetoliposomes combined with
      hyperthermia had a great impact on the Bax/Bcl-2 ratio, which increased to 1.914
      and exhibited a rapid response to induce apoptosis of tumor cells. An in situ
      rabbit liver tumor model was established and used to evaluate the antitumor
      effect of combined hyperthermia and chemotherapy following transcatheter arterial
      embolization with As(2)O(3)/MZF thermosensitive magnetoliposomes. The results
      demonstrated a strong anti-hepatoma effect, with a tumor volume inhibition rate
      of up to 85.22%. Thus, As(2)O(3)/MZF thermosensitive magnetoliposomes may play a
      great role in the treatment of hepatocarcinoma.

PMID- 21730757
TI  - A multi-level capacitor-less memory cell fabricated on a nano-scale strained
      silicon-on-insulator.
AB  - A multi-level capacitor-less memory cell was fabricated with a fully depleted n
      metal-oxide-semiconductor field-effect transistor on a nano-scale strained
      silicon channel on insulator (FD sSOI n-MOSFET). The 0.73% biaxial tensile strain
      in the silicon channel of the FD sSOI n-MOSFET enhanced the effective electron
      mobility to ~ 1.7 times that with an unstrained silicon channel. This thereby
      enables both front- and back-gate cell operations, demonstrating eight-level
      volatile memory-cell operation with a 1 ms retention time and 12 uA memory
      margin. This is a step toward achieving a terabit volatile memory cell.

PMID- 21730758
TI  - General theories for the electrical transport properties of carbon nanotubes.
AB  - We have shown that the general theories of metals and semiconductors can be
      employed to understand the diameter and voltage dependency of current through
      metallic and semiconducting carbon nanotubes, respectively. The current through a
      semiconducting multiwalled carbon nanotube (MWCNT) is associated with the energy
      gap that is different for different shells. The contribution of the outermost
      shell is larger as compared to the inner shells. The general theories can also
      explain the diameter dependency of maximum current through nanotubes. We have
      also compared the current carrying ability of a MWCNT and an array of the same
      diameter of single wall carbon nanotubes (SWCNTs) and found that MWCNTs are
      better suited and deserve further investigation for possible applications as
      interconnects.

PMID- 21730759
TI  - Modeling the conductance and DNA blockade of solid-state nanopores.
AB  - We present measurements and theoretical modeling of the ionic conductance G of
      solid-state nanopores with 5-100 nm diameters, with and without DNA inserted into
      the pore. First, we show that it is essential to include access resistance to
      describe the conductance, in particular for larger pore diameters. We then
      present an exact solution for G of an hourglass-shaped pore, which agrees very
      well with our measurements without any adjustable parameters, and which is an
      improvement over the cylindrical approximation. Subsequently we discuss the
      conductance blockade DeltaG due to the insertion of a DNA molecule into the pore,
      which we study experimentally as a function of pore diameter. We find that DeltaG
      decreases with pore diameter, contrary to the predictions of earlier models that
      forecasted a constant DeltaG. We compare three models for DeltaG, all of which
      provide good agreement with our experimental data.

PMID- 21730760
TI  - Life and death of transcriptional co-activator p300.
AB  - Transcriptional co-activator p300, which contains an intrinsic histone
      acetyltransferase activity, is required for an array of important cellular
      processes. Tight control of p300 function is critical to ensure precise histone
      acetylation and gene activation. Dysregulation of p300 has been implicated in
      many types of diseases and numerous studies have examined the functional
      requirement of p300 to act as a co-activator or as an acetyltransferase for other
      transcription regulators. Few, however, have tackled how p300 itself is regulated
      and if posttranslational modification and spatial distribution are means of p300
      regulation. In this article, we present a current view on the molecular
      mechanisms by which the activity and stability of p300 is regulated.

PMID- 21730761
TI  - From the editor-in-chief: masters of our destiny.

PMID- 21730762
TI  - Interview with Kathleen MacMillan, former provincial chief nursing officer.
      Interview by Michael Villeneuve.

PMID- 21730763
TI  - The call for leadership to influence patient outcomes.

PMID- 21730764
TI  - Are we paying enough attention to clarifying our vision for master's-prepared
      nurses and ensuring that educational programs and workplaces are prepared to help
      achieve that vision? An invitation to engage in an important conversation.

PMID- 21730767
TI  - Master's-prepared novice? Commentary from a new master's-prepared graduate.

PMID- 21730768
TI  - Towards a national report card in nursing: a knowledge synthesis.
AB  - This paper is an abridged version of a knowledge synthesis undertaken to inform
      the proceedings of a collaborative forum of nurse leaders convened under the
      auspices of Health Canada, the Academy of Canadian Executive Nurses, the Canadian
      Nurses Association and Canada Health Infoway for the purpose of discussing the
      development of a nursing report card for Canada. The synthesis summarized the
      state of the science in the measurement of nursing-sensitive outcomes and the
      utilization of nursing report cards - information that informed forum
      participants' dialogue and planning. This condensed version of the synthesis
      focuses on initiatives related to outcomes and performance monitoring in nursing,
      including specific indicators and reporting systems and the development,
      implementation and utilization of nursing report cards.

PMID- 21730769
TI  - Robotic health assistant (Feverkit) for the rational management of fevers among
      nomads in Nigeria.
AB  - The innovation described in this paper was motivated by concern that in Africa,
      parasite resistance to antimalarial drugs is associated with irrational drug use
      where health facilities are inaccessible. However, advancement in digital
      technology, simple diagnostic devices and smart drug packaging inspire innovative
      strategies. The combination of communication technology, rapid diagnostic tools,
      and antibiotic and antimalarial medicines can increase access to evidence-based
      malaria management, reduce mortality and slow the development of resistance to
      drugs. The author initiated development of a solar-powered device (Feverkit)
      programmed with user-interactive capabilities and equipped with a detachable
      laboratory and dispensary for community management of fevers. The operational
      performance of 10 units of the device was evaluated among 20 nomadic Fulani
      communities in northeastern Nigeria. A brief introduction to its parts and
      functions was sufficient for community-selected nomadic caregivers to use it
      competently for managing 207 fever cases in eight weeks, with a 97% (p=.000)
      recovery rate. The Feverkit guided the nomads to distinguish between malaria and
      non-malaria-induced fevers, and thus selectively treat them. Camp communities
      accepted the device and were willing to pay between US$33 and $334 (mean, $113;
      mode, $67) to keep it. Public-private sector collaboration is essential for
      sustaining and scaling up production of the Feverkit as a commercial health
      device for the management of fevers among nomads.

PMID- 21730770
TI  - Making the case for succession planning: who's on deck in your organization?
AB  - In Canada, the nursing shortage is all encompassing, and nurse leaders are needed
      from the bedside to the boardroom. Healthcare organizations and the nursing
      profession lag behind the corporate sector in development of strategic leadership
      succession planning. Contemporary nurse leaders will require all the knowledge,
      skills, attitudes and competencies their predecessors can provide. Effective
      leadership development and succession planning will provide a climate that is
      conducive to the transfer of that knowledge. Providing leadership development
      opportunities within the context of succession planning will assist nurses to
      develop and nurture the leader within. A definitive strategic succession plan may
      mean the difference between success and failure for nurses and their
      organizations.

PMID- 21730771
TI  - Workplace experiences of new graduate nurses.
AB  - Many new graduate nurses find the first year of work stressful and, because of
      this, consider leaving their employer early in their career. The purpose of this
      study is to describe new graduate nurses' experiences during their first year of
      practice and to explore factors that may lead them to consider leaving their
      employer. We held semi-structured interviews with 23 new graduate nurses in New
      Brunswick. Five themes emerged from the data: surviving the first months;
      induction into the hospital culture; struggling to maintain a balance; being a
      nurse: assuming a professional role; and strategic choices: looking at the
      future. The findings suggest that the first year at work continues to be
      difficult for new graduates. Several participants changed jobs during their first
      year, and several others were seriously considering leaving. This study provides
      a more comprehensive understanding of the reasons new graduate nurses decide to
      leave and describes strategies that may assist in retaining this important group
      of healthcare providers.

PMID- 21730772
TI  - Community of practice: a nurse practitioner collaborative model.
AB  - A study was undertaken with nurse practitioners (NPs) in 2008-2009 to examine
      post-legislation role development in British Columbia. The authors used a
      participatory action research approach to engage NPs in social investigation,
      education and action, and to explore, from the participants' perspective, how
      collaboration advances NP role integration in primary healthcare. A particular
      discovery of the study was the Interior Health Authority Community of Practice
      (CoP) established in collaboration with health leaders and NPs. The purpose of
      this paper is to report on the CoP and the five characteristics describing this
      collaborative CoP model, including sanctioned social structure, knowledge
      exchange network, practice discovery and innovation, generating meaning and
      value, and power sharing for strategic improvement. The CoP helped NPs to build
      collegial and collaborative relationships, enhance practice learning and
      competence, extend and apply new knowledge, enrich professional identities, and
      shape health organizational policy and politics. Because healthcare research
      about CoPs is limited, principles of a collaborative CoP model are offered for
      broader healthcare use. The authors conclude that a collaborative CoP model
      addresses the internal interests and needs of participating members while
      attending to the external concerns of the organization, and thus contributes to
      healthcare improvement.

PMID- 21730773
TI  - Potential pitfalls concerning colorectal cancer classification in the seventh
      edition of the AJCC Cancer Staging Manual.

PMID- 21730776
TI  - Routine antibiotics for anorectal abscess: the answer is still no.

PMID- 21730777
TI  - Primary tumor resection in stage IV colorectal cancer: the debate continues.

PMID- 21730778
TI  - Abdominoperineal resection revisited: is positioning an important issue?

PMID- 21730779
TI  - Does adjuvant antibiotic treatment after drainage of anorectal abscess prevent
      development of anal fistulas? A randomized, placebo-controlled, double-blind,
      multicenter study.
AB  - BACKGROUND: The risk of fistula formation is a major concern after incision and
      drainage of an anorectal abscess. OBJECTIVE: Our objective was to the test the
      effects of antibiotic treatment on fistula formation after incision and drainage
      of anorectal abscesses. DESIGN: Randomized, placebo-controlled, double-blind
      study. SETTING: Multicenter trial at 3 teaching hospitals in Turkey. PATIENTS:
      Patients who underwent abscess drainage between September 2005 and January 2008
      were evaluated for eligibility. Exclusion criteria included penicillin allergy,
      antimicrobial agent usage before enrolment, other infection, previous anorectal
      surgery, inflammatory bowel disease, suspicion of Fournier gangrene, secondary
      and recurrent anorectal abscesses, anal fistula at time of the surgery, immune
      compromised states, and pregnancy. INTERVENTION: Patients were randomly assigned
      to receive placebo or amoxicillin-clavulanic acid combination treatment for 10
      days after abscess drainage. MAIN OUTCOME MEASURES: The primary end point was
      rate of anorectal fistula formation at 1-year follow-up. RESULTS: : Of 334
      patients assessed for eligibility, 183 entered the study (placebo, 92;
      antibiotics, 91). Data were available for per-protocol analysis from 151 patients
      (placebo, 76; antibiotics, 75) with a mean age of 37.6 years; 118 patients
      (78.1%) were men. Overall, 45 patients (29.8%) developed anal fistulas during 1
      year follow-up. Fistula formation occurred in 17 patients (22.4%) in the placebo
      group and in 28 patients (37.3%) in the antibiotic group (P = .044). Risk of
      fistula formation was increased in patients with ischiorectal abscess (odds
      ratio, 7.82) or intersphincteric abscess (odds ratio, 3.35) compared with
      perianal abscess. CONCLUSION: Antibiotic treatment following the drainage of an
      anorectal abscess has no protective effect regarding risk of fistula formation.

PMID- 21730780
TI  - Primary colectomy in patients with stage IV colon cancer and unresectable distant
      metastases improves overall survival: results of a multicentric study.
AB  - BACKGROUND: Whether patients with stage IV colon cancer and unresectable distant
      metastases should be managed by primary colectomy followed by chemotherapy or
      immediate chemotherapy without resection of the primary tumor is still
      controversial. OBJECTIVE: This study aimed to evaluate predictive factors
      associated with survival in patients with stage IV colon cancer and unresectable
      distant metastases. DESIGN: This large retrospective multicentric study included
      6 academic hospitals. SETTINGS: This study was conducted at 6 Paris University
      Hospitals (Assistance Publique-Hopitaux de Paris; Saint Antoine, Henri Mondor,
      Ambroise Pare, Hopital Europeen Gorges Pompidou, Bichat, and Avicenne). PATIENTS:
      Between 1998 and 2007, 208 patients with good performance status and stage IV
      colon cancer with unresectable distant metastases received chemotherapy, either
      as initial management or after primary tumor resection. MAIN OUTCOME MEASURES:
      Survival was estimated by use of the Kaplan-Meier method. Factors associated with
      survival were tested by means of a log-rank test. Results were expressed as
      median values with 95% confidence intervals. Factors independently related to
      survival were tested using a Cox regression model adjusted for a propensity
      score. RESULTS: Of the 208 patients, 85 underwent colectomy before chemotherapy,
      whereas 123 were treated with use of primary chemotherapy with or without
      biotherapy. At univariate analysis, the following factors were significantly
      associated with survival: primary colectomy (P = .031), secondary curative
      surgery (P < .001), well-differentiated primary tumor (P < .001), exclusive liver
      metastases (P < .027), absence of need for colonic stent (P = .009), and addition
      of antiangiogenic (P = .001) or anti-epidermal growth factor receptor (P = .013)
      drugs to chemotherapy. After Cox multivariate analysis and after adjusting for
      the propensity score, all of these factors, with the exception of two, colonic
      stent and anti-epidermal growth factor receptor drug, were found to be
      independently associated with overall survival. LIMITATION: This study was
      limited by its retrospective nature. CONCLUSIONS: In a selected population of
      patients with colon cancer and unresectable synchronous distant metastases,
      immediate colectomy followed by chemotherapy in association with targeted therapy
      was associated with longer overall survival. This strategy appears to be the most
      appropriate, especially for those with good performance status, well
      differentiated tumors, and synchronous liver metastases only.

PMID- 21730781
TI  - Prone or lithotomy positioning during an abdominoperineal resection for rectal
      cancer results in comparable oncologic outcomes.
AB  - BACKGROUND: There is debate whether performing the perineal part of the
      abdominoperineal resection in a prone position in comparison with a lithotomy
      position optimizes circumferential resection margins and, subsequently, cancer
      outcomes. OBJECTIVE: The aim of this study was to compare outcomes of patients
      undergoing abdominoperineal in a prone vs a lithotomy position. DESIGN: A single
      center, prospectively maintained colorectal cancer database was queried for
      patients with stages I to III rectal cancer undergoing abdominoperineal resection
      in a prone vs a lithotomy position from 1997 to 2007. Patients were compared with
      respect to demographics, tumor and treatment characteristics, perioperative
      morbidity, and oncologic outcomes. Oncologic outcomes were adjusted for age, ASA
      class, tumor stage, and use of adjuvant treatments. chi2, Fisher exact
      probability test, Wilcoxon rank-sum test, Kaplan-Meier estimates, log-rank sum
      test, and Cox regression models were used for the analysis. P < .05 was
      considered significant. RESULTS: The query returned 168 patients (81 prone and 87
      lithotomy), with a median age of 63 (interquartile range, 52-74) years and a
      median follow-up of 42 (interquartile range, 23-69) months. Prone and lithotomy
      patients were not statistically different regarding demographics, tumor stage,
      rates of R0 resection, number of harvested nodes, perioperative morbidity, follow
      up time, and oncologic outcomes. CONCLUSIONS: Surgical positioning during the
      perineal part of the abdominoperineal resection does not affect perioperative
      morbidity or oncologic outcomes and should be left to the surgeon's discretion.

PMID- 21730782
TI  - Deep pelvic anatomy revisited for a description of crucial steps in extralevator
      abdominoperineal excision for rectal cancer.
AB  - BACKGROUND: Extralevator abdominoperineal excision results in superior oncologic
      outcome for advanced low rectal cancer. The exact definition of surgical
      resection planes is pivotal to achieving negative circumferential resection
      margins. OBJECTIVE: This study aims to describe the surrounding anatomical
      structures that are at risk for inadvertent damage during extralevator
      abdominoperineal excision. DESIGN AND SETTING: Joint surgical and macroanatomical
      dissection was performed in a university laboratory of clinical anatomy. METHODS:
      A stepwise dissection study was conducted according to the technique of
      extralevator abdominoperineal excision by abdominal and perineal approaches in 4
      human cadaveric pelvises. Muscular, fascial, tendinous, and neural structures
      were carefully exposed and related to the corresponding surgical resection
      planes. RESULTS: In addition to the autonomic nerves to be identified and
      preserved during total mesorectal excision, further structures endangered during
      extralevator abdominoperineal excision can be clearly identified. Terminal
      pudendal nerve branches come close to the surgical resection plane at the outer
      surface of the puborectal sling. Likewise, the pelvic plexus and its
      neurovascular bundles embedded within the parietal pelvic fascia extend close to
      the apex of the prostate where the parietal pelvic fascia has to be divided.
      These neural structures converge in the region of the perineal body, an area that
      provides no "self-opening" planes for surgical dissection. Thus, the necessity to
      sharply detach the anorectal specimen anteriorly from the perineal body and the
      superficial transverse perineal muscle bears the risk of both inadvertent damage
      of the aforementioned anatomical structures and perforation of the specimen.
      LIMITATIONS: The study focused primarily on the macroscopic topography relevant
      to the surgical procedure, so that previously published histologic examinations
      were not performed. CONCLUSION: The present anatomical dissection study
      highlights those anatomical landmarks that require clear identification for the
      successful achievement of both negative circumferential resection margins and
      preservation of urogenital functions during extralevator abdominoperineal
      excision.

PMID- 21730783
TI  - Low rectal cancer: abdominoperineal resection or low Hartmann resection? A
      postoperative outcome analysis.
AB  - BACKGROUND: In distal rectum cancers, when the sphincters are not affected and it
      is not possible to perform a coloanal anastomosis because of the presence of
      comorbidities or the advanced age of the patient, a low Hartmann resection with
      total mesorectal excision can be performed. Low Hartmann resection is usually
      considered to be a shorter procedure and to have an inferior morbidity compared
      with abdominoperineal resection of the rectum. OBJECTIVE: This study aimed to
      compare the postoperative outcome of a series of patients with low rectal cancer
      who have undergone either low Hartmann resection or abdominoperineal resection.
      DESIGN: This study is a retrospective analysis of data collected in a prospective
      database. SETTINGS: This study was conducted in a specialized Colorectal Unit,
      Department of Surgery, of a tertiary teaching hospital. PATIENTS: Patients who
      underwent low Hartmann or abdominoperineal resection for rectal cancer between
      1996 and 2009 at our specialized Colorectal Unit were considered. INTERVENTIONS:
      The main interventions were low Hartmann resection vs abdominoperineal resection.
      MAIN OUTCOME MEASURES: The main outcome measures were 60-day morbidity and
      mortality. RESULTS: The pelvic abscess rate was 12.2% in patients who underwent
      low Hartmann resection and 3.0% in those who underwent abdominoperineal resection
      (P = .02). The reoperation rate was 14.6% in the Hartmann group and 3.8% in the
      abdominoperineal group (P = .013). The rehospitalization rates in the Hartmann
      and abdominoperineal groups were 7.3% and 0.7% (P = .015). No differences were
      found in the other variables analyzed. At multivariate analysis, the surgical
      technique performed was the only independent risk factor for pelvic abscess
      development, readmission, and reoperation. LIMITATIONS: : This study was limited
      by its retrospective nature. CONCLUSION: In our series, low Hartmann resection
      was associated with higher pelvic abscess, reoperation, and readmission rates.
      These findings suggest that in patients with rectal cancer without sphincter
      infiltration and who are unsuitable for coloanal anastomosis, abdominoperineal
      resection should be a valid alternative to low Hartmann resection.

PMID- 21730784
TI  - Risk factors for fecal incontinence after intersphincteric resection for rectal
      cancer.
AB  - BACKGROUND: Restoration of bowel continuity is a major goal after surgical
      treatment of rectal cancer. Intersphincteric resection allows sphincter
      preservation in low rectal cancer but may have poor functional results, including
      frequent bowel movements, urgency, and incontinence. OBJECTIVE: This study aimed
      to evaluate long-term functional outcome after intersphincteric resection to
      identify factors predictive of good continence. DESIGN: Descriptive observational
      study. SETTING: Follow-up of surgery in tertiary care university hospital.
      PATIENTS: Eligible patients were without recurrence 1 year or more after surgery
      for low rectal cancer. INTERVENTION: Intersphincteric resection. MAIN OUTCOME
      MEASURES: : Bowel function was assessed with a standardized questionnaire sent to
      patients. Functional outcome was considered as good if the Wexner score was 10 or
      less. Univariable and multivariable regression analyses were used to evaluate
      impact of age, gender, body mass index, tumor stage, tumor location, distance of
      the tumor from the anal verge and from the anal ring, type of surgery, colonic
      pouch, height of the anastomosis, pelvic sepsis, and preoperative radiotherapy on
      functional outcome. RESULTS: Of 125 eligible patients, 101 responded to the
      questionnaire. Median follow-up was 51 (range, 13-167) months. In multivariate
      analyses, the only independent predictors of good continence were distance of the
      tumor greater than 1 cm from the anal ring (OR, 5.88; 95% CI, 1.75-19.80; P =
      .004) and anastomoses higher than 2 cm above the anal verge (OR, 6.59; 95% CI,
      1.12-38.67; P = .037). LIMITATIONS: The study is limited by its retrospective,
      observational design and potential bias due to possible differences between those
      who responded to the questionnaire and those who did not. CONCLUSIONS: Patient
      characteristics do not appear to influence functional outcome at long-term follow
      up after intersphincteric resection. The risk of fecal incontinence depends
      mainly on tumor level and height of the anastomosis.

PMID- 21730785
TI  - Sacral nerve stimulation for fecal incontinence: long-term outcomes.
AB  - BACKGROUND: Numerous studies advocate the short-term benefits of sacral nerve
      stimulation for fecal incontinence, but there has been a paucity of studies on
      longer-term outcomes. OBJECTIVE: The objective of this study was to report the
      long-term outcome of sacral nerve stimulation performed for fecal incontinence at
      a single institution. PATIENTS AND DESIGN: Between January 2004 and May 2007, 53
      patients underwent definitive sacral nerve stimulation for fecal incontinence at
      our institution. Prospectively recorded baseline information, including Wexner
      incontinence scores and standard short-form (SF-12) health survey scores, were
      compared with scores at follow-up. RESULTS: Forty-one patients were available for
      long-term follow-up with a mean duration of 51 months. The median Wexner score
      decreased from a baseline of 11.5 (range, 3.0-18.0) to 8.0 (range, 0.0-18.0) at
      follow-up. The mean difference in Wexner score was 2.7 (P < .001). There was no
      statistically significant change in SF-12 physical scores, but a small but highly
      significant change occurred in SF-12 mental scores. The median SF-12 mental
      domain score was 49.5 (range, 15.0-62.1) at baseline, and 57.0 (range, 20.0-64.0)
      at follow-up, with a mean difference of 4.5 (P = .006). Subgroup analysis
      performed comparing patients with or without prior intersphincteric silicon
      biomaterial implants demonstrated a mean difference in Wexner score of -3.5 (no
      implant) vs 0.0 (previous implant), with P < .09 (not statistically significant).
      CONCLUSIONS: Sacral nerve stimulation results in a statistically significant
      improvement in fecal incontinence scores in the long term.

PMID- 21730786
TI  - Menopause and obstetric history as risk factors for fecal incontinence in women.
AB  - BACKGROUND: Fecal incontinence is a highly prevalent condition, especially in
      women. However, few data on prevalence in women attending primary care are
      available, particularly regarding the presence of risk factors. OBJECTIVE: The
      aim of this study was to determine characteristics of women with fecal
      incontinence and to analyze obstetric history and menopause as potential risk
      factors. DESIGN: Observational study with a cross-sectional design. SETTINGS:
      Patients in primary care at 10 health care centers in Barcelona, Spain. MAIN
      OUTCOME MEASURES: Fecal incontinence was defined as loss of flatus or
      liquid/solid stool occurring at least monthly. Data on the following variables
      were collected by face-to-face interviews and patient questionnaires: demographic
      and clinical characteristics, obstetric history, menopause data, fecal
      incontinence, and quality of life. Univariable and multivariable analyses were
      performed to study the association of potential risk factors with fecal
      incontinence. RESULTS: The study included 332 women with a mean age of 60.8 (SD,
      17.8) years. The prevalence of fecal incontinence was 12.0% (40/332). Flatus
      incontinence was reported in 27 patients (67.5%), liquid stool incontinence in 25
      (62.5%), and solid stool incontinence in (19) 47.5%. On multivariable analysis,
      the only independent risk factors for fecal incontinence were an obstetric
      history of complicated deliveries (instrumentation or podalic presentation; OR,
      3.66; 95% CI, 1.54-8.68, P = .003) and menopause (OR, 5.67; 95% CI, 1.35-23.78; P
      = .018). LIMITATIONS: The cross-sectional design hampered identification of the
      time at which the impact of menopausal status occurred, and data obtained from
      patient interviews was subject to recall bias. CONCLUSIONS: Complicated
      deliveries are risk factors for fecal incontinence in women. Fecal incontinence
      appears to be more prevalent in menopausal women.

PMID- 21730787
TI  - The prognostic significance of extramural deposits and extracapsular lymph node
      invasion in colon cancer.
AB  - BACKGROUND: The status of resected lymph nodes in colon cancer determines
      prognosis and further treatment. The American Joint Committee on Cancer staging
      system has designated extramural nodules as nonnodal disease and classified them
      as extensions of the T category in the sixth edition and as site-specific tumor
      deposits in the seventh edition. Extracapsular lymph node extension is an
      established poor prognostic indicator in many cancers. Its significance in colon
      cancer has not been extensively investigated. OBJECTIVE: This study aimed to
      determine the prognostic significance of extramural nodules and extracapsular
      lymph node extension in colon cancer. DESIGN: A pathological review of 114 stage
      III and 80 stage II colon cancers was undertaken to analyze for p-T stage, p-N
      stage (using the fifth, sixth, and seventh editions), and the size and contour of
      nodal and extramural deposits. Multivariate Cox regression models were used to
      determine the prognostic significance of clinicopathological parameters on
      survival estimates. RESULTS: According to the sixth and seventh editions of the
      guidelines, extramural deposits were present in 29% and 31% of patients with
      stage III colon cancer and in 5% of patients with stage II colon cancer.
      Extracapsular lymph node invasion was present in 68% of cases. Multivariate
      analysis demonstrated that lymph node ratio, extracapsular lymph node extension,
      and adjuvant chemotherapy were independent prognostic factors affecting 5-year
      disease-free survival. The same 3 variables, in addition to extramural deposits,
      were independent prognostic factors affecting overall survival. The presence of
      extramural deposits was associated with an 11% 5-year survival, and extracapsular
      lymph node invasion was associated with a 33% 5-year survival. CONCLUSIONS:
      Instead of extramural nodules being included as part of the T category or as site
      specific tumor deposits, they should perhaps be classified in the metastasis
      category. This has major prognostic implications and may broaden the application
      of a number of adjuvant agents.

PMID- 21730788
TI  - Predictive factors for pulmonary metastases after curative resection of rectal
      cancer without preoperative chemoradiotherapy.
AB  - OBJECTIVE: The aim of this study was to clarify the actuarial incidence of
      pulmonary metastases and risk factors for pulmonary metastases after curative
      resection of rectal cancer without preoperative chemoradiotherapy. DESIGN: This
      study was a retrospective review. PATIENTS: Data for 314 patients who underwent
      R0 resection for rectal cancer without preoperative chemoradiotherapy from 2000
      to 2006 were reviewed. The mean duration of follow-up was 57.0 months. RESULTS:
      Pulmonary metastases developed in 41 patients. Mean duration from rectal surgery
      to identification of pulmonary metastases was 21.1 months. Surgery for pulmonary
      metastases was performed first for 19 patients (46.3%), and all patients achieved
      R0 surgery. Multivariate analysis revealed that tumor depth (T3 to T4), lymph
      node ratio (>0.091), and tumor location (anal canal) were significant independent
      risk factors for pulmonary metastases. Five-year actuarial incidence of pulmonary
      metastasis increased significantly with increased numbers of risk factors (0
      factors, 1.1%; 1 factor, 13.2%; >=2 factors, 40.1%). In terms of lateral pelvic
      lymph node involvement, the number of lateral pelvic lymph node involvements
      (>=4) and the distribution of lateral pelvic lymph node metastases (bilateral)
      were significant risk factors for pulmonary metastases. CONCLUSIONS: The present
      study clearly demonstrated predictive factors for pulmonary metastases after R0
      resection of rectal cancer without preoperative chemoradiotherapy. Actuarial
      incidence of pulmonary metastases was significantly related to the number of risk
      factors present. The data from the present study should facilitate the
      establishment of novel algorithms for predicting pulmonary metastases after
      resection of rectal cancer, which may lead to the appropriate surveillance
      strategies after rectal surgery.

PMID- 21730789
TI  - Long-term efficacy of the button fistula plug in the treatment of Ileal pouch
      vaginal and Crohn's-related rectovaginal fistulas.
AB  - BACKGROUND: Several new techniques have been described for the management of anal
      fistulas. The anal fistula plug has received much attention. The button plug
      adaptation has been heralded for use in rectovaginal and ileal pouch-vaginal
      fistulas. OBJECTIVE: The aim of this study was to report the long-term efficacy
      of the button plug in patients with such fistulas. DESIGN: All women with ileal
      pouch-vaginal and rectovaginal fistulas secondary to Crohn's disease who
      underwent insertion of a novel button fistula plug between May 2008 and November
      2009 were prospectively evaluated. RESULTS: At long-term follow up of a median of
      118 (interquartile range, 81.5-129.0) weeks, none of the 11 patients (0%) with
      ileal pouch-vaginal fistulas were considered to have healed, whereas 4 of the 9
      patients (44%) with rectovaginal fistulas had healed. Each of these 4 patients
      whose treatment was successful were nonsmokers with an etiology of Crohn's
      disease and achieved complete closure of the fistula tract after one procedure,
      and none had been defunctioned. All repeat procedures failed. CONCLUSION: The
      button fistula plug may be an option for patients with Crohn's-related
      rectovaginal fistulas, albeit with the caveat of advising patients of a less than
      50% success rate, but not for patients with ileal pouch-vaginal fistulas. Repeat
      attempts cannot be justified.

PMID- 21730790
TI  - The changing picture of high-grade anal intraepithelial neoplasia in men who have
      sex with men: the effects of 10 years of experience performing high-resolution
      anoscopy.
AB  - BACKGROUND: Ten years ago, we published findings from anal dysplasia screening in
      a metropolitan surgical practice where the majority of men who have sex with men
      had biopsy-proven high-grade anal intraepithelial neoplasia. OBJECTIVE: This
      study aimed to determine the effect of 10 years of experience in anal dysplasia
      screening on the prevalence of high-grade anal intraepithelial neoplasia. DESIGN:
      A retrospective chart review was performed of all anal cytology results of 1189
      men who have sex with men screened in a 1-year period, with subsequent high
      resolution anoscopy and biopsy as necessary. PATIENTS: The patients studied were
      men who have sex with men. MAIN OUTCOME MEASURE: The main outcome measure was
      biopsy-proven high-grade anal intraepithelial neoplasia. RESULTS: : There were
      315 (37.2%) biopsy-verified instances of high-grade anal intraepithelial
      neoplasia. Regression analysis determined that age, HIV status, infection by high
      risk human papillomavirus, and abnormal cytology results were significant
      predictors of high-grade anal intraepithelial neoplasia. In a 1-year period, the
      number of men who have sex with men screened was nearly 7 times greater than in
      the 2-year period studied 10 years earlier. LIMITATIONS: We did not separately
      analyze patients who had previously been treated for high-grade anal
      intraepithelial neoplasia. CONCLUSIONS: Severity of cytology and infection with
      high-risk human papillomavirus are the most significant predictors of high-grade
      anal intraepithelial neoplasia, underscoring the importance of anal dysplasia
      screening. Our ability to identify high-grade anal intraepithelial neoplasia has
      improved with 10 years of experience performing high-resolution anoscopy.

PMID- 21730791
TI  - Outcome of a modified York Mason technique in men with iatrogenic urethrorectal
      fistula after radical prostatectomy.
AB  - BACKGROUND: Urethrorectal fistula formation is a rare but devastating
      complication after radical prostatectomy. Reconstructive surgery is usually
      required, and one surgical option is the York Mason procedure. OBJECTIVE: We
      present our experience with a modified York Mason technique for the surgical
      management of urethrorectal fistula. DESIGN: Retrospective review of medical
      records. SETTING: Tertiary care university medical center. PATIENTS: Consecutive
      male patients with urethrorectal fistula due to radical prostatectomy who
      underwent York Mason repair between 1998 and 2009. INTERVENTION: All patients
      initially received both a urinary and a bowel diversion as the first step of the
      treatment. The second step consisted of a modification of the York Mason
      technique in which the approach began with a parasacrococcygeal incision
      extending from the coccyx to the anal verge. MAIN OUTCOME MEASURES: All patients
      were seen 3, 6, and 12 months after surgery and yearly thereafter to assess the
      resolution of clinical functional disorders and the Wexner fecal incontinence
      score. RESULTS: The study included 10 men with a mean age of 63.7 (range, 50-80)
      years who had urethrorectal fistula after open retropubic prostatectomy (n = 6)
      or after laparoscopic prostatectomy (n = 4). Confined prostate cancer (pT2) was
      found in 7 patients and extracapsular extension of the tumor (pT3) in 3 patients.
      Urethrorectal fistula was discovered because of fecaluria in 6 patients and
      pneumaturia in 6. The mean time from surgery to York Mason repair was 15 (range,
      4-42) months. Five patients had each previously undergone 1 unsuccessful repair
      procedure. The mean operative time was 81 (range, 60-130) minutes and the mean
      hospital stay was 6 days. No fecal incontinence or anal stenosis developed after
      York Mason repair. No recurrence of urethrorectal fistula occurred during a mean
      follow-up of 24 (range, 18-38) months. LIMITATIONS: Lack of objective fecal
      continence data. CONCLUSIONS: : York Mason repair appears to be a safe and
      effective approach for management of urethrorectal fistula. The rates of fistula
      closure and symptom resolution are encouraging, and patients show rapid
      postoperative recovery with minimal morbidity. Thus, York Mason repair should
      always be considered for treatment of urethrorectal fistula after radical
      prostatectomy.

PMID- 21730792
TI  - The use of silver nylon in preventing surgical site infections following colon
      and rectal surgery.
AB  - BACKGROUND: Patients who undergo colorectal surgery have up to a 30% chance of
      developing a surgical site infection postoperatively. Silverlon is a silver nylon
      dressing designed to prevent surgical site infections, but only anecdotal
      evidence has previously supported its efficacy. OBJECTIVE: The aim of this study
      was to evaluate the effect of silver nylon dressings in patients undergoing
      colorectal surgery. DESIGN: We performed a prospective, randomized, controlled
      trial comparing a silver nylon dressing with gauze dressings in patients
      undergoing elective colorectal surgery. SETTING: The study was performed at a
      university-based, tertiary referral center. PATIENTS: We studied patients
      undergoing elective colorectal surgery with an abdominal skin incision of at
      least 3 cm. INTERVENTION: Patients were randomly assigned to receive either a
      silver nylon or a gauze dressing. MAIN OUTCOME MEASURES: The primary end point
      was surgical site infection occurring within 30 days of surgery. RESULTS: One
      hundred ten patients were enrolled in the study and were randomly assigned to 1
      of 2 treatment groups. After a 30-day follow-up period, the incidence of surgical
      site infection was lower in the silver nylon group compared with the control
      group (13% vs 33%, P = .011). Twenty-five patients in the study developed
      superficial surgical site infections, 5 in the silver nylon group and 14 in the
      control group (P = .021). Two patients in the study group developed deep wound
      infections compared with 4 in the control group (P = .438). Multivariate analysis
      revealed that patients in the control group had a 3-fold increase in risk of
      infection compared with patients in the silver nylon group (P = .013).
      LIMITATIONS: A limitation of this study is that the members of the surgical team
      were not blinded to the treatment groups. CONCLUSION: Silver nylon is safe and
      effective in preventing surgical site infection following colorectal surgery.

PMID- 21730793
TI  - Influence of Crohn's disease risk alleles and smoking on disease location.
AB  - OBJECTIVE: : Our objective is to assess the effect of genetic and environmental
      factors on Crohn's disease location. DESIGN: : We identified 628 patients with
      Crohn's disease within the Washington University database (April 2005 through
      February 2010) that had complete information on 31 Crohn's disease-associated
      genotypes and clinical information on disease location (L1 to L4), smoking, sex,
      race, and age at diagnosis. For statistical reasons, the 3 major NOD2 alleles
      (rs2066844, rs2066845, and rs2066847) were grouped together. Logistic regression
      incorporating all of the genotypes and clinical covariates, including smoking,
      was performed with stepwise variable selection and by best subset selection.
      RESULTS: : Stepwise variable selection selected 3 major covariates, composite
      NOD2 genotype, smoking, and TNFSF15 genotype, which are also the 3 covariates
      selected by the best subset method. Whereas the NOD2 genotype and smoking are
      positively associated with ileal (L1 + L3) disease, the TNFSF15 genotype is
      positively associated with isolated colonic (L2) disease. LIMITATIONS: : The
      ability to detect disease site associations in this single-center study may be
      limited by the population size, low allelic frequency, and/or low odds ratio of
      certain Crohn's disease risk alleles. CONCLUSION: : These results indicate that
      NOD2 genotype, smoking status, and TNFSF15 genotype should be included as
      covariates in assessing the effect of genetic and environmental factors on
      Crohn's disease site location.

PMID- 21730794
TI  - Gene expression of vascular endothelial growth factor A, thymidylate synthase,
      and tissue inhibitor of metalloproteinase 3 in prediction of response to
      bevacizumab treatment in colorectal cancer patients.
AB  - BACKGROUND: Regimens containing bevacizumab and 5-fluorouracil have achieved
      substantial progress in the treatment of colorectal cancer. However, individual
      responses to bevacizumab vary widely in regard to efficacy and toxicity.
      OBJECTIVE: To be able to select patients who would benefit from bevacizumab, we
      aimed to establish a predictor model for response to bevacizumab therapy based on
      gene expression profiles. DESIGN AND SETTING: Retrospective analysis of tumor
      samples in the laboratory. PATIENTS: The patient population comprised 25 patients
      with metastatic colorectal cancer treated with bevacizumab with either modified
      FOLFOX6 or FOLFIRI, from whom tumor samples were available for gene expression
      analysis. MAIN OUTCOME MEASURES: Response Evaluation Criteria in Solid Tumors
      were used to classify patients as responders or nonresponders to chemotherapy.
      Gene-expression profiles were determined with both microarray analysis and
      quantitative, real-time reverse-transcriptase polymerase chain reaction, and
      responders were compared with nonresponders, correcting for multiple comparisons.
      Genes that discriminated between groups on both analyses with the greatest
      accuracy were selected for the predictive model. Between-group differences in
      protein expression were confirmed with polymerase chain reaction and
      immunohistochemical staining. RESULTS: From 19 probes that differentiated between
      responders and nonresponders on microarray analyses, we identified 13 genes that
      were differentially expressed between responders and nonresponders on both
      microarray and real-time reverse-transcriptase polymerase chain reaction. A model
      using the genes for vascular endothelial growth factor-A, thymidylate synthase,
      and tissue inhibitor of metalloproteinase 3 predicted response to bevacizumab
      therapy with an accuracy of 96%, sensitivity of 90.9% (10/11), specificity of
      100% (14/14), positive predictive value of 100% (10/10), and negative predictive
      value of 93.3% (14/15). The protein expression of vascular endothelial growth
      factor-A, thymidylate synthase, and tissue inhibitor of metalloproteinase 3
      correlated with the findings of mRNA expression analyses. LIMITATIONS: Validation
      of the model in a different cohort of patients is necessary. CONCLUSIONS: The
      present predictive model based on quantitative, real-time, reverse-transcriptase
      polymerase chain reaction assessment of vascular endothelial growth factor-A,
      thymidylate synthase, and tissue inhibitor of metalloproteinase 3 may enable
      selection of colorectal cancer patients who would benefit from bevacizumab
      therapy.

PMID- 21730795
TI  - Surveillance after colorectal cancer resection: a systematic review.
AB  - BACKGROUND: Surveillance programs are widely accepted as an integral part of the
      treatment plan provided to patients after surgical treatment of colorectal
      cancer. Despite an enormous amount of research performed regarding these
      programs, there is still uncertainty regarding what is appropriate surveillance.
      OBJECTIVE: We sought to systematically review recent literature regarding
      outcomes achieved with different types of surveillance programs for patients with
      surgically treated colorectal cancer. DATA SOURCES: A search of the PubMed
      database was performed to identify studies published in the English language
      between January 2000 and January 2010. STUDY SELECTION: We included 2 types of
      studies in our systematic review: first, comparative studies where 2 or more
      surveillance strategies were applied and outcomes compared; second, single-cohort
      studies where the outcomes of a single surveillance strategy were reported. MAIN
      OUTCOME MEASURES: Cancer-related outcomes included survival, recurrence detection
      rate, and the ability of a recurrence to be resected with curative intent.
      RESULTS: Our review found 15 studies meeting our inclusion criteria. Of these, 9
      were comparative (4 randomized trials) and 6 were single-cohort studies. One
      study reported a better survival rate among patients who received more intensive
      follow-up. The vast majority of recurrences occurred within 3 years. LIMITATIONS:
      Our review found that the recent literature regarding the efficacy of
      surveillance is inconclusive, largely because of the small sample sizes and the
      heterogeneity in the surveillance programs and outcomes reported. CONCLUSIONS:
      Future randomized trials need to focus on larger sample sizes, and experimental
      designs should isolate specific elements of surveillance to better understand how
      each element contributes to improvements in patient outcomes. Risk stratification
      and duration of surveillance are key elements of surveillance strategies that
      also deserve focused investigation.

PMID- 21730796
TI  - Laparoscopic resection for rectal cancer and circumferential margin: is it time
      to move on?

PMID- 21730797
TI  - Single-port access laparoscopic reversal of Hartmann operation.
AB  - BACKGROUND: Single-port access offers cosmetic advantages in addition to the well
      recognized benefits of standard multiport laparoscopic surgery, and can be
      performed with the use of standard straight instruments. We describe a technique
      of single-port access reversal of Hartmann colostomy by use of the colostomy site
      for access. METHODS: After routine skin preparation and laparoscopic setup, the
      colostomy is mobilized from its mucocutaneous border, and the anvil of a circular
      stapler is secured to the distal lumen. By the use of a GelPoint system with 3 or
      4 trocars, the intra-abdominal adhesions are divided and the splenic flexure is
      mobilized to achieve sufficient access to the abdominal and pelvic cavities and
      proximal colonic mobility. The rectal stump is mobilized to the mid rectum,
      starting from the posterior mesorectal fascia around to the anterior rectal wall.
      A tension-free colorectal anastomosis is secured with a standard circular
      stapling device inserted transanally, and leak tested. The colostomy wound is
      closed in standard fashion. RESULTS: Five patients underwent single-port access
      reversal of Hartmann resection (4 diverticular perforations and 1 pT3N0 colon
      cancer), with a mean operating time of 155 (range, 137-187) minutes and a median
      length of stay of 3 (range, 2-11) days. There were no conversions, major surgical
      morbidity, or deaths. CONCLUSION: Single-port access reversal of Hartmann
      colostomy through the stoma site is safe, and it offers additional cosmetic
      advantages with no apparent additional morbidity in comparison with standard
      multiport surgery.

PMID- 21730798
TI  - Extracorporeal membrane oxygenation as rescue therapy for methadone-induced
      pulmonary edema.
AB  - Opioid-induced pulmonary edema has been previously reported, but its mechanism
      remains unclear. The use of extracorporeal membrane oxygenation as rescue therapy
      for methadone-induced pulmonary edema has not been reported in the literature. We
      describe 2 cases of methadone ingestion complicated by pulmonary edema, acute
      respiratory distress syndrome, and circulatory failure successfully managed with
      venoarterial extracorporeal membrane oxygenation.

PMID- 21730799
TI  - Perforated appendicitis and appendicolith in a child presenting as
      intussusception: a case report.
AB  - Simultaneous diagnoses of intussusception and appendicitis in the same patient
      have rarely been described in the pediatric literature. A case of a 30-month-old
      boy is presented with an initial diagnosis of intussusception that was
      successfully reduced by air contrast enema. When the patient's condition
      deteriorated, a diagnostic search surprisingly revealed a missed perforated
      appendicitis with an appendicolith that had been part of the intussusception. The
      patient's hospitalization and surgical course is described along with a
      discussion of the intermingling of intussusception and appendicitis in a young
      child. This case illustrates the need to consider alternative diagnoses when a
      patient's course takes an unexpected and confusing turn.

PMID- 21730800
TI  - A case of functional asplenia and pneumococcal sepsis.
AB  - Asplenia may refer to the spleen's surgical removal, functional impairment, or
      congenital absence. It is a risk factor for the development of severe bacterial
      infection. Functional asplenia is likely the most common presentation of this
      entity and has many etiologies. Those that are previously undiagnosed may present
      completely well until an episode of overt sepsis develops. The true incidence of
      mortality secondary to functional asplenia remains elusive. As lifetime mortality
      remains exceedingly high in the asplenic population regardless of etiology,
      markers of hyposplenism are important to detect. The present report describes an
      infant with trisomy 21 and previously undiagnosed functional asplenia who
      ultimately experienced overwhelming pneumococcal sepsis with features of
      Waterhouse-Friderichsen syndrome and died within 12 hours of initial
      presentation. It is a poignant reminder of what features to be cognizant of on
      peripheral blood smear in a previously well child, who may be at risk for a
      devastating consequence.

PMID- 21730801
TI  - Pediatric button battery and small magnet coingestion: two cases with different
      outcomes.
AB  - Ingestion of button batteries and ingestion of 2 or more small magnets have both
      been increasingly recognized as having high potential for injury. Coingestion of
      a button battery and a small magnet has only rarely been described but has the
      potential for both ischemic injury due to the tight magnetic adherence and the
      electric current injury from the button battery. We report 2 cases of button
      battery and small magnet coingestion; one required surgical repair of an
      important bowel injury, while the other had a benign course. We discuss the
      management and role of radiography in these cases and the potential factors to
      consider when predicting which patients will have serious injury and which will
      do well.

PMID- 21730802
TI  - A neonate with high-outflow congestive heart failure and pulmonary hypertension
      due to an intracranial arteriovenous malformation.
AB  - Congestive heart failure in the newborn period is uncommon and is most commonly
      related to congenital structural heart disease. However, the differential
      diagnosis is broad and includes arrhythmias, congenital or acquired myopathies,
      sepsis, severe anemia, or other conditions leading to high-output cardiac
      failure. Here we report on a 4-day-old girl with high-output heart failure due to
      a congenital cerebral arteriovenous malformation.

PMID- 21730803
TI  - Nontraumatic spontaneous acute subdural hematoma in identical teenage twins 1
      year apart.
AB  - OBJECTIVES: Acute subdural hematoma (ASDH) is a life-threatening injury with a
      high mortality rate. Most ASDH cases are a result of trauma; nontraumatic causes
      are relatively rare with an incidence rate of 3% to 5%. We report an unusual
      series of 2 patients, identical twins, who had nontraumatic subdural hematomas 1
      year apart, one at age 15 and the other at age 16. METHODS (CASE PRESENTATIONS):
      Identical twin brothers presented 1 year and 10 days apart to an academic medical
      center after incurring confusion, decreased mental functioning, and a subsequent
      comatose state. The injuries occurred while the patients were playing football,
      but there was no evidence of traumatic blow to the head in either brother.
      RESULTS: Both patients had computed tomographic scans and both underwent
      emergency surgery for hematoma evacuation. Both patients recovered full
      neurological function and remained healthy 12 years after surgery. CONCLUSIONS:
      Acute spontaneous subdural hematoma is an emergent medical condition that may
      result in rapid neurological decline and must be addressed in a timely fashion.
      After evacuation of the hematoma, intracranial pressure decreases and cerebral
      perfusion pressure increases, which may allow normal perfusion of the brain.
      Consequently, prompt recognition and evacuation of an ASDH can drastically
      improve prognosis. Rarely, subdural hematoma can occur without head injury and
      should be in the differential diagnosis of athletes who rapidly become comatose.

PMID- 21730804
TI  - Hypomanic switching during influenza infection without intracranial infection in
      an adolescent patient with bipolar disorder.
AB  - Manic switching, which is mood changing from depression to mania, induced by
      intracranial viral infections have been previously reported. However, manic
      switching induced by influenza infection without intracranial viral infection in
      a patient with bipolar disorder (BD), has not been previously reported. We report
      a patient with adolescent BD who showed a first episode of hypomanic switching
      during influenza B infection without intracranial viral infection. In addition to
      neurological monitoring, careful psychiatric interventions for hypomanic state is
      very important to prevent inappropriate treatment of BD and reduce the risk of
      suicide attempts in cases presenting with hypomanic symptoms during influenza
      infection.

PMID- 21730805
TI  - Infectious aortitis: a rare cause of chest pain in a child.
AB  - Infectious aortitis (IA) is a life-threatening bacterial infection that occurs
      almost exclusively in adults. Only 1 case of IA had been previously reported in a
      child. We present a case of IA that occurred in a 6.5-year-old previously healthy
      girl who was seen in our emergency department because of fever and chest pain of
      immediate onset. She underwent a thorough evaluation but died of aortic rupture
      before the correct diagnosis was established. The etiology, clinical
      presentation, diagnosis, and treatment of IA are discussed.

PMID- 21730806
TI  - Ectopic atrial tachycardia in an infant with transient erythroblastopenia of
      childhood.
AB  - Transient erythroblastopenia of childhood is a self-limited anemia occurring in
      previously healthy children, secondary to temporary cessation of erythrocyte
      production. Although the precise etiology is unclear, most cases are associated
      with a viral illness. The anemia may be severe, with associated pallor,
      tachypnea, and tachycardia; treatment is supportive. We present an unusual case
      of a child with viral-induced transient erythroblastopenia of childhood and
      associated ectopic atrial tachycardia, requiring therapy with antiarrhythmics.

PMID- 21730807
TI  - Recurrent abdominal pain and hematuria.

PMID- 21730808
TI  - Recurrent viral-induced compartment syndrome.
AB  - Rhabdomyolysis and compartment syndrome are rare but a limb-threatening
      complication of viral myositis. Because of the potential for severe consequences
      of compartment syndrome, clinicians should maintain a high index of suspicion
      when examining children with rhabdomyolysis due to viral myositis. We report a
      case of recurrent bilateral thigh compartment syndrome in a patient with
      influenza A, subtype pandemic H1N1-2009. CASE: An 8-year-old girl with a history
      of rhabdomyolysis, acute renal failure, and compartment syndrome secondary to
      parainfluenza infection that resulted in release of her lower limb compartments
      presented with a 3-day history of flu symptoms and increasing bilateral thigh
      pain. Compartment syndrome was confirmed by intracompartmental pressure
      measurements and comparison of intracompartmental pressure measurements to
      diastolic blood pressure. The compartments were released. She also experienced
      acute renal failure, which was treated by continuous renal replacement therapy
      and hemodialysis. At her most recent orthopedic follow-up, she was doing well.
      CONCLUSIONS: This is the first reported case of recurrent rhabdomyolysis and
      compartment syndrome as a complication of viral myositis. This case highlights
      the importance of maintaining a high index of suspicion for compartment syndrome
      in the child with viral myositis.

PMID- 21730810
TI  - Scorpion envenomation and antivenom therapy.
AB  - Scorpion envenomation is a dangerous and common global event that can result in a
      variety of toxic clinical effects. These are typically managed with supportive
      care or antivenom. Antivenom use is controversial because of conflicting evidence
      of effectiveness for adrenergic toxicity. However, both controlled and
      uncontrolled studies have shown that antivenom is effective in resolving
      neuromotor toxicity associated with envenomations by the scorpions of genus
      Centruroides.

PMID- 21730811
TI  - Renal stones: evolving epidemiology and management.
AB  - The incidence of renal stones in adults has increased significantly over time.
      Although published evidence is somewhat limited, during the last 10 years, there
      have been reports of 4-fold increase in the number of children evaluated for
      nephrolithiasis, and of those, a 7-fold increase in diagnosis of stone disease.
      The etiology of stone formation has shifted over time, with a transition from
      infectious causes to metabolic causes. It was our goal in this review of the
      literature on pediatric renal stone disease to further highlight the changing
      epidemiology and etiology as well as provide a framework for appropriate clinical
      evaluation and use of diagnostic tools when approaching a patient with suspected
      renal stone disease. We also provide guidance regarding treatment and prevention
      of renal stone disease in children.

PMID- 21730812
TI  - Rickets.

PMID- 21730813
TI  - ECGs in the ED.

PMID- 21730814
TI  - Short-term sevoflurane anesthesia for painless lumbar puncture in children.

PMID- 21730816
TI  - Significance of gastroesophageal refluxate in relation to physical, chemical, and
      spatiotemporal characteristics in symptomatic intensive care unit neonates.
AB  - Gastroesophageal reflux disease (GERD) is a frequent consideration in intensive
      care unit neonates. We tested the hypothesis that symptoms in GERD are dependent
      on the spatiotemporal and physicochemical characteristics of reflux events by
      evaluating the symptom sensitivity index (SSI) and symptom index (SI) in relation
      to the refluxate characteristics. Thirty symptomatic neonates (30.7 +/- 0.8 wk
      gestation) were evaluated using manometry and pH-impedance methods. During 704.3
      h of recordings, 2063 gastroesophageal reflux (GER) were observed; 54% of the GER
      were associated with symptoms. Defined by physical characteristics, there were
      51.3% liquid, 29.1% gas, and 19.6% mixed GER. Defined by chemical
      characteristics, there were 48.5% acid and 51.5% nonacid GER. Defined by most
      proximal extent, 79.2% were supra-UES (upper esophageal sphincter) and 20.8% were
      infra-UES. Higher SSI was noted with pH-only events (p < 0.0001 versus pH
      impedance events). Higher SI was noted with movement symptoms (versus sensory, p
      = 0.04). In a subset analysis, the frequencies of GER events, acid clearance
      time, and SSI were all greater in chronic lung disease versus none (p < 0.001).
      In conclusion, clinical significance of symptoms as measured by SSI and SI and
      characterization of spatial-temporal-physical-chemical nature of GER events as
      defined by pH-impedance methods clarifies the definition of GERD.

PMID- 21730818
TI  - Growing rods for scoliosis in spinal muscular atrophy: structural effects,
      complications, and hospital stays.
AB  - STUDY DESIGN: Retrospective analysis of patients with spinal muscular atrophy
      (SMA) treated with growing rod (GR) instrumentation for scoliosis. OBJECTIVE: To
      evaluate structural effectiveness, complications, and length of hospital stay
      associated with GRs for scoliosis in SMA and to compare values with those of
      infantile and juvenile idiopathic scoliosis (IIS/JIS). SUMMARY OF BACKGROUND
      DATA: Most studies evaluate GR effectiveness in all patients. We specifically
      examined SMA and IIS/JIS. METHODS: We searched a multicenter database and found
      15 patients with SMA and scoliosis treated with GRs for 54 +/- 33 months.
      Radiographic measurements, complications, and hospital stay durations were
      compared with those of 80 GR patients with IIS/JIS observed for 43 +/- 31 months.
      Measures of rib collapse, including T6:T10 mean rib-vertebral angle and T6:T12
      thoracic width, were compared. Student t test was used to compare SMA and IIS/JIS
      values (significance level, P = 0.05). RESULTS: Primary radiographic measurements
      in patients with SMA improved from preoperative to latest follow-up as follows:
      curve, 89 degrees  +/- 19 degrees  to 55 degrees  +/- 17 degrees ; pelvic
      obliquity, 31 degrees  +/- 14 degrees  to 11 degrees  +/- 10 degrees ; space
      available-for-lung ratio, 0.86 +/- 0.15 to 0.94 +/- 0.21; and T1-S1 length grew
      8.7 +/- 3.2 cm. Rib collapse continued despite GR treatment in SMA but not in
      IIS/JIS. Hospital stays were longer for SMA than for IIS/JIS for lengthening
      procedures (P = 0.01) and trended to be longer for initial surgery (P = 0.08) and
      final fusion (P = 0.06). Patients with SMA and IIS/JIS experienced, respectively,
      0.5 and 1.1 major complications per patient (P = 0.02). CONCLUSION: GRs improve
      trunk height and the space-available-for-lung ratio while controlling curve and
      pelvic obliquity in young patients with SMA with severe scoliosis, but they do
      not halt rib collapse. For patients with SMA, hospital stays were longer than
      those for patients with IIS/JIS, whereas the rate of major complications was
      lower.

PMID- 21730819
TI  - Health-related quality of life in subjects with low back pain and knee pain in a
      population-based cohort study of Japanese men: the Research on Osteoarthritis
      Against Disability study.
AB  - STUDY DESIGN: Cross-sectional surveys of health-related quality of life (QOL) in
      subjects with low back pain and knee pain using a population-based cohort.
      OBJECTIVE: The purpose of the present study was to clarify the impact of low back
      pain and knee pain on QOL in men. In addition, we analyzed the impacts of
      vertebral fracture (VFx), lumbar spondylosis, and knee osteoarthritis (OA) on the
      magnitude of QOL loss in men with low back pain and knee pain. SUMMARY OF
      BACKGROUND DATA: Low back pain and knee pain are major public health issues
      causing disability among the elderly men, but there were no population-based
      studies to compare the impact of low back pain on QOL with that of knee pain in
      Japanese men. METHODS: From 3040 participants in the Research on Osteoarthritis
      Against Disability study, data from 767 men older than 40 years who completed
      questionnaires (mean age = 69.7 years) were examined. To carry out the QOL
      assessment, the Medical Outcomes Study Short Form 8 (SF-8) and EuroQol (EQ-5D)
      were used. We examined the association of low back pain and knee pain with QOL.
      Furthermore, we also examined the presence of VFx and the severity of lumbar
      spondylosis and knee OA with the magnitude of QOL loss in men with low back pain
      and knee pain, respectively. RESULTS: The impact of low back pain on QOL was
      larger than that of knee pain. In men with low back pain, there were few
      associations between Kellgren-Lawrence grade and QOL, whereas VFx was associated
      with physical QOL. For men with knee pain, Kellgren-Lawrence grade equal to 4
      knee OA was associated with QOL. CONCLUSION: This study revealed that low back
      pain has a larger impact than knee pain on QOL. Furthermore, low back pain with
      VFx is strongly associated with physical QOL loss.

PMID- 21730820
TI  - PAX2 expression in Wilms tumors and other childhood neoplasms.
AB  - PAX2 plays an important role in kidney development; although small studies have
      demonstrated PAX2 expression in Wilms tumors (WT), comprehensive studies on
      formalin-fixed tissue are lacking. Thus, we systematically evaluated PAX2
      immunohistochemical staining in a retrospective study of pediatric WT, as
      compared with other pediatric tumors. We stained formalin-fixed, paraffin
      embedded sections from 39 WT, 6 nephrogenic rests, 8 non-Wilms renal tumors, and
      43 nonrenal pediatric small round cell tumors with 2 different PAX2 polyclonal
      antibodies. PAX2 demonstrated strong, diffuse staining of epithelial and blastema
      components of WT (97% of cases). PAX2 stained WT stroma in fewer cases (23%), but
      80% of anaplastic foci were positive. Nephrogenic rests, 1 case of metanephric
      adenoma, and 1 pediatric renal cell carcinoma were also PAX2 positive; other
      pediatric renal tumors were negative. Neuroblastoma, primitive neuroectodermal
      tumor/Ewings, and T-cell acute lymphoblastic lymphoma (ALL) were PAX2 negative.
      However, PAX2 weakly stained some cases of B-cell ALL rhabdomyosarcoma (RMS) was
      also stained, especially alveolar RMS (83%), with less staining of embryonal RMS
      (13%). One of the antibodies also stained maturing myoid cytoplasm of WT and RMS.
      This study shows that PAX2 is a sensitive marker of WT (sensitivity 97%), but
      PAX2 shows weak-to-moderate-intensity nuclear staining of RMS and B-cell ALL,
      somewhat limiting its utility. However, PAX2 may be a helpful marker in certain
      diagnostic situations. We speculate that RMS and B-cell ALL staining could be due
      to antibody cross-reactivity with PAX family members with known expression in RMS
      and B-cell ALL.

PMID- 21730821
TI  - Extracelluar matrix metalloproteinase as a novel target for pancreatic cancer
      therapy.
AB  - The objective of this study was to evaluate extracellular matrix
      metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic cancer
      murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1
      and 3-7, whereas MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2.
      Dosing with anti-EMMPRIN antibody started immediately after implantation for
      groups 1-3 (residual tumor model) and at 21 days after cell implantation for
      groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti
      EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, whereas the other
      groups served as the control. In the residual tumor model, tumor growth of anti
      EMMPRIN-treated group was successfully arrested for 21 days (15 +/- 4 mm(3)),
      which was significantly lower than that of the EMMPRIN knockdown group (80 +/- 15
      mm(3); P=0.001) or the control group (240 +/- 41 mm(3); P<0.001). In the
      established tumor model, anti-EMMPRIN therapy lowered tumor volume increase by
      approximately 40% compared with the control, regardless of the dose amount. Ki67
      expressed cell density of group 5 was 939 +/- 150 mm(-2), which was significantly
      lower than that of group 4 (1709 +/- 145 mm(-2); P=0.006). Microvessel density of
      group 5 (30 +/- 6 mm(-2)) was also significantly lower than that of group 4 (53
      +/- 5 mm(-2); P=0.014), whereas the microvessel size of group 5 (191 +/- 22
      MUm(2)) was significantly larger than that of group 4 (113 +/- 26 MUm(2);
      P=0.049). These data show the high potential of anti-EMMPRIN therapy for
      pancreatic cancer and support its clinical translation.

PMID- 21730822
TI  - Reactive oxygen species-mitochondria pathway involved in FV-429-induced apoptosis
      in human hepatocellular carcinoma HepG2 cells.
AB  - FV-429 is a newly synthesized flavonoid with a bis(2-hydroxyethyl) amino propoxy
      substitution. In this study, we investigate the anticancer effect of FV-429 both
      in vivo and in vitro. These data have shown that FV-429 could significantly
      inhibit tumor growth in mice inoculated with Heps hepatoma cells without evident
      toxicity. After the treatment of FV-429 (40 mg/kg), the inhibitory rate of tumor
      weight was 52.12%. Then, we performed diamidinophenylindole staining and annexin
      V/propidium iodide double-staining assay to investigate the apoptosis induced by
      FV-429 in HepG2 cells. Further research revealed that FV-429 induced apoptosis
      through the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl
      2 ratios, collapse of mitochondrial membrane potential, the transposition of
      apoptotic-inducing factor and cytochrome c, caspase-3 and caspase-9 activation,
      and degradation of poly (ADP-ribose) polymerase. The accumulation of reactive
      oxygen species induced by FV-429 in HepG2 cells was also observed. Moreover, the
      mitogen-activated protein kinases, the downstream effect of reactive oxygen
      species accumulation including c-Jun N-terminal kinase and p38 mitogen-activated
      protein kinases, could be activated by FV-429. Taken together, our results
      provided a mechanistic framework for further exploration of FV-429 as a novel
      chemotherapy for human tumors.

PMID- 21730823
TI  - Postoperative levels of cardiac troponin versus CK-MB and high-sensitivity C
      reactive protein for the prediction of 1-year cardiovascular outcome in patients
      undergoing vascular surgery.
AB  - OBJECTIVE: This study evaluated comparatively the predictive value of
      postoperative cardiac troponin I (cTnI), creatinine kinase (CK)-MB, and high
      sensitivity C-reactive protein (hs-CRP) in 1-year cardiovascular mortality and
      morbidity in patients undergoing elective vascular surgery. METHODS: A total of
      295 consecutive patients undergoing elective noncardiac vascular surgery were
      prospectively followed-up over a period of 12 months. The levels of cTnI, CK-MB,
      and hs-CRP were measured preoperatively and 24 h after operation. The primary
      endpoint was the composite of cardiovascular death, nonfatal acute myocardial
      infarction, ischemic stroke, and unstable angina. RESULTS: The primary endpoints
      occurred in 11 patients (3.8%). Receiver operating characteristic curve analysis
      showed that postoperative cTnI was a strong predictor of a cardiovascular event
      during 1-year follow-up (area under the curve, 0.852; P<0.001). Areas under the
      curve for hs-CRP and for CK-MB were 0.734 (P=0.008) and 0.494 (P=0.947). A
      threshold cTnI value of 0.4 ng/ml was highly associated with the occurrence of a
      cardiovascular event, with a sensitivity of 80% and specificity of 81%.
      Furthermore, cTnI levels provided a significantly better prediction than CK-MB
      levels (P=0.009) and tended to be superior to hs-CRP (P=0.2). CONCLUSION:
      Postoperative cTnI levels seem to be superior to CK-MB and hs-CRP levels for the
      prediction of 1-year cardiovascular mortality and morbidity in patients
      undergoing elective vascular surgery.

PMID- 21730824
TI  - Systematic approaches to smoking cessation in the cardiac setting.
AB  - PURPOSE OF REVIEW: Constituents of tobacco smoke are prothrombotic and
      atherogenic and causative factors in the development of coronary heart disease
      (CHD). Smoking cessation is the single most important intervention to reduce
      morbidity and mortality in smokers with CHD. This review presents contemporary
      information regarding treatments for smoking cessation in the setting of CHD.
      RECENT FINDINGS: The beneficial effects of smoking cessation may be mediated by
      improvements in endothelial function. Failure to quit smoking in those with CHD
      is a typical consequence of nicotine addiction. Practical counseling and
      pharmacotherapy [nicotine replacement therapy (NRT), bupropion, and varenicline]
      are well tolerated and effective treatments for CHD patients attempting to quit
      smoking. Treatments initiated in hospital following a CHD-related event or
      procedure are more effective than those initiated outside the hospital setting.
      Extending medication use beyond the initial treatment phase is the most promising
      means of preventing relapse. Financial coverage for smoking cessation
      pharmacotherapy improves quit rates. The routine provision of pharmacotherapy and
      practical counseling in the CHD setting can be assured by implementing proven,
      systematic approaches to smoking cessation treatment. SUMMARY: Smoking cessation
      is a fundamental priority in smokers with CHD. Systematic approaches to ensure
      that cessation assistance is provided by clinicians and to improve cessation
      outcomes for smokers are effective and available.

PMID- 21730825
TI  - Tobacco smoke and cardiovascular risk: a call for continued efforts to reduce
      exposure.
AB  - PURPOSE OF REVIEW: This review will summarize contemporary data regarding the
      cardiovascular effects of tobacco exposure. In particular, this review will
      highlight recent data that focuses on the magnitude of continued exposure both in
      the United States and abroad, the cardiovascular risks of tobacco exposure
      despite improvements in medical therapy, and the important effects of low levels
      of exposure including secondhand smoke (SHS). RECENT FINDINGS: Recent data
      demonstrates that the current burden of tobacco exposure both in the United
      States and worldwide remains large. Despite improvements in medical therapy for
      cardiovascular disease the cardiovascular effects of tobacco exposure are
      substantial. Recent data also demonstrates that even intermittent smoking and
      exposure to SHS have important cardiovascular effects. SUMMARY: The
      cardiovascular effects of tobacco exposure, including even low levels from SHS,
      remain important. Continued efforts to reduce exposure to our patients are
      critical for improved cardiovascular health.

PMID- 21730826
TI  - The polypill to prevent cardiovascular disease: physicians' perspectives.
AB  - PURPOSE OF REVIEW: The term 'polypill' denotes a single-pill combination of drugs
      for reducing cardiovascular disease events. The 'polypill strategy' refers to
      making such a pill available to the population based on age (e.g. 55 years)
      rather than individually as a result of a clinical decision. This review
      summarizes recent studies describing physicians' perspectives regarding the
      polypill. RECENT FINDINGS: Among 58 physicians in Sri Lanka, 86% likely would
      prescribe a polypill for primary prevention if a large trial showed it reduced
      the risk of major cardiovascular disease events. A study of 952 US physicians
      found that 83% likely would prescribe a polypill for high-risk patients and 62%
      likely would do so for moderate-risk patients. Among physicians in both
      countries, degree of risk reduction was an important factor in willingness to
      prescribe. Other factors considered important were side effects and cost.
      Physicians had low agreement with forgoing risk factor level monitoring in
      patients taking a polypill. The majority (89%) of US physicians surveyed would
      not want a polypill available without a prescription. SUMMARY: Current physician
      acceptance of the polypill seems moderate to high, at least when considering a
      clinical approach to its use. As trial publications emerge, it is possible that
      physician perspectives may evolve toward greater acceptance of a population
      health approach to the implementation of a polypill.

PMID- 21730827
TI  - Optimal pharmacotherapy to combat the atherogenic lipid triad.
AB  - PURPOSE OF REVIEW: A lipid triad involving an atherogenic dyslipidemia
      characterized by moderate/high LDL-C, low HDL-C, and elevated triglyceride (TG)
      occurs in numerous clinical settings associated with high cardiovascular risk.
      This article focuses on optimizing treatment of atherogenic dyslipidemias
      involving this lipid triad, emphasizing niacin-based or fibrate-based therapies.
      RECENT FINDINGS: Niacin-based therapies comprehensively improve the atherogenic
      lipid profile, lead to atherosclerosis regression, and exert benefits across a
      spectrum of cardiovascular endpoints in studies based on limited patient numbers.
      Fibrates impact TG, HDL-C, and LDL-C according to lipid phenotype and underlying
      metabolic abnormality. In a recent meta-analysis, fibrates significantly reduced
      major cardiovascular events (-10%) and coronary events (-13%) across a wide range
      of lipid phenotypes, but had no impact on stroke, sudden death, or mortality. The
      Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial in type 2
      diabetic patients similarly showed no significant effect of fenofibrate +
      simvastatin (vs. simvastatin) on nonfatal myocardial infarction, nonfatal stroke,
      or cardiovascular death; a subgroup (17%) with marked atherogenic dyslipidemia
      trended toward benefit. Both niacin and fibrates attenuate vascular inflammation
      but the potential clinical relevance is indeterminate. SUMMARY: Optimal
      cardiovascular risk reduction in patients exhibiting the lipid triad requires
      integrated pharmacotherapy to normalize LDL-C, HDL-C, TGs, and potentially
      lipoprotein(a). Ongoing studies may provide definitive evidence of the impact of
      niacin plus statins on cardiovascular outcomes.

PMID- 21730828
TI  - Stress testing: the case for the standard treadmill test.
AB  - PURPOSE OF REVIEW: This review examines the diagnostic and prognostic performance
      of the standard exercise treadmill test (ETT) in comparison to stress imaging
      procedures. This topic is timely and relevant due to increasing healthcare
      expenditures and the substantially lower cost of the ETT. RECENT FINDINGS: The
      most important goal of noninvasive testing is to identify patients with left main
      or three-vessel coronary artery disease (CAD) or severely reduced left
      ventricular ejection fraction (LVEF) less than 35%. These patient subsets
      demonstrate a survival advantage when treated with coronary artery bypass
      grafting (severe CAD) or a defibrillator (LVEF <35%). This benefit is not present
      for patients with one-vessel or two-vessel CAD or preserved LVEF. For patients
      who have a normal resting ECG, studies have shown that the standard ETT is as
      accurate as imaging for identifying these high-risk patients. Outcome of patients
      with a low-risk exercise treadmill score is excellent. SUMMARY: The standard ETT
      should be the initial test in patients presenting for evaluation of CAD with the
      following characteristics: (1) ability to exercise adequately; (2) normal resting
      ECG; and (3) no prior revascularization. Applying this strategy should not
      sacrifice prognostic accuracy and should result in significant cost savings.

PMID- 21730829
TI  - Stress cardiac magnetic resonance.
AB  - PURPOSE OF REVIEW: Coronary artery disease (CAD) is associated with significant
      morbidity and mortality. Several noninvasive imaging techniques such as stress
      echocardiography, stress nuclear studies, computed tomography coronary
      angiography, and, most recently, stress cardiovascular magnetic resonance (CMR)
      have enhanced the accuracy and efficiency of evaluation of patients. RECENT
      FINDINGS: The diagnostic capabilities of CMR have increased substantially over
      the past 20 years due to hardware and software advances. Today, CMR has a number
      of unique advantages over other imaging modalities - primarily because it
      provides a view of the entire heart without limitations from inadequate imaging
      windows or body habitus. Furthermore, along with stress imaging for inducible
      wall motion or perfusion abnormalities, CMR provides a comprehensive examination
      with concurrent evaluation of the ejection fraction, aorta, pericardium, and
      valves all without the inherent risks of radiation administration or contrast
      exposure. SUMMARY: The purpose of this article is to review the current state of
      stress CMR for both detection of significant disease and the prognostication of
      future cardiac events. Clinical data will demonstrate that stress CMR is
      accurate, with detection in a broad population of patients similar to or better
      than reported using other noninvasive stress imaging techniques. Moreover,
      patients with a normal adenosine stress CMR scan have an excellent prognosis on
      follow-up with no adverse cardiovascular outcomes. Thus, CMR perfusion stress
      testing has been deemed appropriate for the evaluation of chest pain syndromes in
      patients with intermediate probability of coronary artery disease (CAD) and for
      ascertaining the physiologic significance of indeterminate coronary artery
      lesions.

PMID- 21730830
TI  - Recent advances in stress echocardiography.
AB  - PURPOSE OF REVIEW: This article reviews the recent advances in stress
      echocardiography, with particular attention to articles published in 2010 and
      2011. It summarizes the developments in the diagnostic and prognostic
      capabilities of stress echocardiography, discusses new data regarding the safety
      of stress echocardiography, and highlights emerging roles for stress
      echocardiography in the areas of left ventricular assist devices, cardiac
      transplantation, strain-rate echocardiography, and myocardial perfusion imaging.
      RECENT FINDINGS: Stress echocardiography represents a well validated tool in the
      diagnosis and assessment of patients with known or suspected coronary artery
      disease. Recently, data have emerged supporting the prognostic capabilities of
      stress echocardiography in patients with various levels of systolic dysfunction,
      diastolic abnormalities, and valvular heart disease. New studies continue to
      document the safety of stress echocardiography, particularly with regard to
      arrhythmias, neuropsychiatric symptoms, dosing of dobutamine, and intravenous
      contrast. Studies are now suggesting that stress echocardiography may play novel
      roles in the evaluation of patients with left ventricular assist devices or
      potential donors for cardiac transplantation. Technologic developments in
      myocardial contrast perfusion imaging, three-dimensional imaging, and strain-rate
      echocardiography will continue to advance the field. SUMMARY: Stress
      echocardiography represents a dynamic, versatile, and well validated tool for the
      noninvasive assessment of patients with a wide spectrum of cardiovascular
      diseases.

PMID- 21730831
TI  - Complement and the antiphospholipid syndrome.
AB  - PURPOSE OF REVIEW: The antiphospholipid antibody syndrome (APS) is characterized
      by arterial or venous thrombosis or pregnancy morbidity in patients with
      persistent antiphospholipid antibodies (aPL). Experimental data supporting
      activation of the complement cascade has provided critical insight into the
      underlying pathophysiology of aPL-induced pregnancy loss and thrombosis. RECENT
      FINDINGS: Although the mechanism by which pregnancy loss and thrombosis is
      incompletely elucidated, studies using mice deficient in complement components
      and specific inhibitors to complement have demonstrated that activation of
      complement contributes to fetal loss, growth restriction and thrombosis.
      Inhibition of complement activation can prevent these complications. Use of a
      specific complement inhibitor to C5 has been used successfully in a patient with
      catastrophic APS undergoing renal transplantation. SUMMARY: Activation of
      complement plays an important role in the pathogenesis of aPL-induced pregnancy
      morbidity and thrombosis. This understanding has been advanced primarily using
      mouse models of APS and clinical studies in patients with APS are needed.
      Although there is currently no specific complement-targeted therapy approved for
      APS, developing and evaluating complement-targeted therapies in patients with APS
      are warranted. Complement inhibition may provide a novel upstream treatment
      option for patients with APS compared with the current standard treatment of
      anticoagulation.

PMID- 21730832
TI  - Kindlin: helper, co-activator, or booster of talin in integrin activation?
AB  - PURPOSE OF REVIEW: The modulation of integrin affinity is central to platelet and
      leukocyte function. Two proteins, talin and kindlin, that interact with distinct
      regions of integrin cytoplasmic domains, have been shown to play essential roles
      in inducing the high affinity integrin conformation required for platelet and
      leukocyte adhesive interactions.Here we highlight some of the key studies that
      have described roles for talin and kindlin in integrin function and discuss
      several models that explain how talin and kindlins might work together to
      regulate integrin activation. RECENT FINDINGS: Genetic deletion of kindlin-3 in
      mice results in platelet and leukocyte adhesive dysfunction associated with
      profoundly impaired activation of multiple classes of integrins, a phenotype
      similar to that observed in talin-deficient platelets and leukocytes. Since this
      initial report three years ago, numerous studies have provided important clues to
      how kindlins activate integrins and, in some cases, the relationship between
      kindlins and talin in integrin activation. SUMMARY: Clearly, talin and kindlins
      are key regulators of integrin affinity. Future experiments that define precisely
      how these molecules work in concert should provide important insights into the
      terminal signaling events that activate integrins.

PMID- 21730833
TI  - Recent advances in heparin-induced thrombocytopenia.
AB  - PURPOSE OF REVIEW: Heparin-induced thrombocytopenia (HIT) is a prothrombotic
      complication of heparin therapy caused by antibodies against platelet factor
      4/heparin complexes. Progress in our understanding of HIT has translated to
      improvements in treatment and patient outcomes. The objective of this review is
      to examine recent advances and highlight areas of future inquiry in the
      epidemiology, diagnosis, and management of this potentially fatal disorder.
      RECENT FINDINGS: Risk factors for the development of HIT related to heparin
      administration are well described. Recent identification of host-related risk
      factors adds to our understanding of disease epidemiology. The limited
      specificity of clinical diagnosis and widely used immunologic assays for HIT
      results in frequent overdiagnosis. Novel clinical decision rules and laboratory
      assays to improve diagnosis are in development. Fondaparinux, bivalirudin, and
      desirudin have recently been added to the HIT armamentarium. SUMMARY: Despite
      these advances, critical issues remain to be addressed. Future research efforts
      will focus on the identification of novel clinical risk factors and biomarkers
      that will enable recognition of individuals at greatest risk, optimization of
      diagnostic strategies and use of currently available therapeutics, and
      development of new drugs that not only reduce thrombotic complications, but also
      minimize bleeding risk, are well tolerated in patients with organ dysfunction,
      and facilitate transition to outpatient therapy.

PMID- 21730834
TI  - A new look at blood coagulation factor V.
AB  - PURPOSE OF REVIEW: Factor V plays an essential role in hemostasis and has a
      profound influence on thrombin generation. The aim of this review is to highlight
      recent advances in our understanding of the biology of factor V which shed light
      on the variable bleeding tendencies in severe factor V deficiency. Furthermore,
      new mechanistic insights responsible for maintaining factor V as an inactive
      procofactor will be discussed. RECENT FINDINGS: The bleeding manifestation of
      severe factor V-deficient patients varies dramatically. Phenotypic modifiers of
      the bleeding predisposition in these patients have recently been identified.
      These include platelet factor V and, surprisingly, plasma tissue factor pathway
      inhibitor, which is significantly reduced in these patients. An important step in
      robust thrombin generation is the activation of factor V to factor Va. In a
      mechanism distinct from factor VIII, factor V activation involves proteolytic
      removal of inhibitory and conserved sequences from the large central B domain
      which exposes binding sites for factor Xa and possibly prothrombin. Taking
      advantage of this mechanism, certain Australian snakes have a unique form of
      factor V in their venom with these inhibitory sequences removed, thereby creating
      a potent constitutively active procoagulant cofactor. SUMMARY: Basic biochemical
      and clinical studies continue to move our understanding of factor V forward. It
      is apparent that there is much to be learned about parahemophilia and factor V
      activation, two seemingly well studied areas of research. A full understanding of
      each may provide unanticipated insights into ways to modulate factor V/Va
      function for therapeutic benefit.

PMID- 21730835
TI  - Factor XI and XII as antithrombotic targets.
AB  - PURPOSE OF REVIEW: Arterial and venous thrombosis are major causes of morbidity
      and mortality, and the incidence of thromboembolic diseases increases as a
      population ages. Thrombi are formed by activated platelets and fibrin. The latter
      is a product of the plasma coagulation system. Currently available anticoagulants
      such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa
      target enzymes of the coagulation cascade that are critical for fibrin formation.
      However, fibrin is also necessary for terminating blood loss at sites of vascular
      injury. As a result, anticoagulants currently in clinical use increase the risk
      of bleeding, partially offsetting the benefits of reduced thrombosis. This review
      focuses on new targets for anticoagulation that are associated with minimal or no
      therapy-associated increased bleeding. RECENT FINDINGS: Data from experimental
      models using mice and clinical studies of patients with hereditary deficiencies
      of coagulation factors XI or XII have shown that both of these clotting factors
      are important for thrombosis, while having minor or no apparent roles in
      processes that terminate blood loss (hemostasis). SUMMARY: Hereditary deficiency
      of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the
      intrinsic pathway of coagulation, impairs thrombus formation and provides
      protection from vascular occlusive events, while having a minimal impact on
      hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation
      to a greater extent than to normal hemostasis, pharmacological inhibition of
      these coagulation factors may offer the exciting possibility of anticoagulation
      therapies with minimal or no bleeding risk.

PMID- 21730836
TI  - Recently recognized platelet agonists.
AB  - PURPOSE OF REVIEW: The story of platelet activation is complex, involving many
      intertwined and overlapping pathways and processes that continue to expand in
      complexity. This review will cover some of the recent novel mediators and
      receptors identified to be important in platelet activation. RECENT FINDINGS:
      Many newly discovered platelet activators and receptors are not strong platelet
      agonists, but rather are important modifiers of platelet activation, and thus
      represent potentially novel targets to blunt, but not totally prevent, platelet
      activation and thrombus formation. The diversity of platelet activation mediators
      and receptors also expands as we learn more about the disease processes that are
      either initiated or accelerated by platelets. Although platelets are a unique
      cell type with a unique role in thrombosis, they share a surprising amount in
      common with the molecules and machinery present in synaptic termini and immune
      cells. Many of these secreted molecules have important roles in platelet
      activation. SUMMARY: Many newly identified platelet activators are weak agonists.
      These represent intriguing targets for platelet inhibitor development or shed
      light on the overlap between inflammation and thrombosis.

PMID- 21730837
TI  - Laser-assisted dacryocystorhinostomy: a viable treatment option?
AB  - PURPOSE OF REVIEW: Improvements in endoscopic instrumentation and evolving laser
      technologies have renewed interest in laser-assisted endonasal applications, and
      an increasing number of lacrimal surgeons have focused on laser-assisted
      approaches to dacryocystorhinostomy (DCR). The purpose of this review was to
      assess the clinical efficacy of laser-assisted DCR techniques with a particular
      focus on the endocanalicular approach and to describe various laser systems and
      their associated tissue effects. RECENT FINDINGS: Recent studies of
      endocanalicular laser DCR suggest favorable success rates that are comparable
      with external and endonasal endoscopic DCR, although there is a shortage of
      robust, prospective, randomized studies. SUMMARY: Recent evidence suggests that
      endocanalicular laser DCR is a well tolerated, viable treatment option for
      nasolacrimal duct obstruction in selected patients with favorable results and
      shorter operative times. More recent studies seem to suggest improvements in
      success rates compared with older studies, although additional, well designed,
      comparative studies are needed.

PMID- 21730838
TI  - Current concepts in the management of periocular infantile (capillary)
      hemangioma.
AB  - PURPOSE OF REVIEW: To review and evaluate the medical literature on new
      treatments for periocular infantile (capillary) hemangioma. Recent studies have
      shown a promising new therapy for infantile hemangioma using nonselective beta
      blockers, including oral propranolol and topical timolol. RECENT FINDINGS:
      Conventional treatments for infantile hemangioma include the use of
      corticosteroids, laser, surgery, and immunomodulator therapy. Recently, systemic
      and topical beta-blockers have been used to successfully treat infantile
      hemangioma. The drugs' mechanism of action remains uncertain, but plausible
      theories include vasoconstriction, modulation of pro-survival signal transduction
      pathways, and endothelial cell apoptosis. Whereas no life-threatening adverse
      events from beta-blocker treatment have been described, there have been reports
      of bradycardia, hypotension, bronchospasm, hypoglycemia, and electrolyte
      disturbances resulting from systemic use of propranolol to treat infantile
      hemangioma. Sleep and gastrointestinal disturbances have also been frequently
      reported. Topical timolol application for localized, superficial tumors may
      confer similar efficacy as oral propranolol while reducing systemic effects.
      SUMMARY: Despite the recent explosion of interest surrounding this novel
      treatment, current treatment and protocol-monitoring recommendations are based
      largely on the experience of individual centers. Several randomized controlled
      studies are currently underway, the results of which will guide future standard
      of-care treatment for infantile hemangioma.

PMID- 21730839
TI  - The current state of ptosis repair: a comparison of internal and external
      approaches.
AB  - PURPOSE OF REVIEW: Posterior approach ptosis repair has made a resurgence over
      the last decade. The purpose of this review is to examine the history of
      posterior approach ptosis repair and the events that have led to its current
      favorable status. RECENT FINDINGS: The evolution of the posterior and anterior
      approach ptosis surgeries has resulted in two favored techniques for involutional
      ptosis repair: the Muller muscle-conjunctiva resection (MMCR) and the external
      levator advancement. Each procedure has strong and prominent proponents in the
      oculoplastic surgery community. Recently, the MMCR has converted surgeons who
      have previously favored the external levator advancement. A number of factors
      have influenced this recent elevation of the MMCR including differing opinions on
      the cause of involutional ptosis, the mechanism by which the MMCR works, the
      predictability and speed of the MMCR, and the current reimbursements for ptosis
      repair by insurance companies. SUMMARY: The recent preference for posterior
      approach ptosis surgery, in particular the MMCR, is multifactorial. In order to
      understand the evolution of opinions about the procedure, a historical knowledge
      of involutional ptosis and ptosis repair is necessary.

PMID- 21730840
TI  - Congenital anophthalmia: current concepts in management.
AB  - PURPOSE OF REVIEW: The introduction of hydrogel socket and orbital expanders has
      modified the approach towards the rehabilitation of congenital anophthalmia. This
      study highlights the most recent advances for the treatment of congenital
      anophthalmia based on personal experience and the review of recent literature.
      RECENT FINDINGS: Hydrogel socket expanders may be positioned as an out-patient
      procedure with topical anaesthesia, using cyanoacrylate glue as opposed to
      temporary tarsorraphy. Increased orbital volume has been confirmed by computed
      tomography (CT) scan or magnetic resonance imaging (MRI) following early dermis
      fat graft in children with congenital anophthalmia. An orbital tissue expander
      made of an inflatable silicone globe sliding on a titanium T-plate and secured to
      the lateral orbital rim appears to be effective to stimulate orbital bone growth
      and development. SUMMARY: Congenital anophthalmia has a complex cause with both
      genetic and environmental factors involved. The ideal treatment is simultaneous
      expansion of the eyelids, socket and orbital bones, and it should begin after
      birth as soon as possible. Socket expansion with self-inflating expanders is a
      useful technique, although custom-made conformers may produce similar results.
      Dermis-fat grafts are another reasonable option as an orbital implant, following
      adequate lid and socket expansion.

PMID- 21730841
TI  - The pathophysiology of thyroid eye disease: implications for immunotherapy.
AB  - PURPOSE OF REVIEW: Thyroid eye disease (TED) is a poorly understood autoimmune
      manifestation most commonly associated with Graves' disease. Current nonspecific
      treatment paradigms offer symptomatic improvement but fail to target the
      underlying pathogenic mechanisms, and thus do not significantly alter the long
      term disease outcome. The purpose of this review is to provide an update of the
      current understanding of the immunopathogenesis of TED and explore these
      mechanisms for targeted immunotherapy. RECENT FINDINGS: Orbital fibroblasts are
      integral to the pathogenesis of TED and may modulate immune responses by
      production of cytokines and hyaluronan in response to activation of shared
      autoantigens including thyrotropin receptor and insulin-like growth factor-1
      receptor. Bone marrow-derived fibrocytes share many of these phenotypic and
      functional features, suggesting a link between systemic and site-specific
      disease. Use of targeted immunotherapies in TED is limited, though data from the
      use Rituximab (RTX), a B-cell depleting agent, are encouraging. Sustained
      clinical response has been seen with RTX in several reports, despite return of
      peripheral B-cell levels to pretreatment levels. Additionally, this response
      appears to be independent of cytokine and antibody production, suggesting
      modulation of antigen presentation as a mechanism of its effect. SUMMARY:
      Progressive advances in the understanding of the immunopathogenesis of TED
      continue to spur clinical trials utilizing targeted immune therapies. Continued
      understanding of the molecular mechanisms of disease will expand potential
      treatments for TED patients and obviate the need for reconstructive surgical
      therapies.

PMID- 21730842
TI  - A review of surgical techniques to correct upper eyelid retraction associated
      with thyroid eye disease.
AB  - PURPOSE OF REVIEW: We review the literature pertinent to surgical correction of
      upper eyelid retraction resulting from thyroid eye disease (TED). RECENT
      FINDINGS: Although novel nonsurgical treatment of TED-upper eyelid retraction has
      been described, with botulinum A toxin and hyaluronic acid; graded full-thickness
      blepharotomy remains the mainstay of treatment for the condition. SUMMARY: Graded
      full-thickness anterior blepharotomy provides predictable, reproducible results
      and is a simple surgical procedure to master. For patients who cannot undergo
      surgical intervention, botulinum toxin offers a novel nonsurgical answer to lid
      retraction, but may be complicated by overcorrection and introduces an additional
      variable that needs to be considered when following the patient.

PMID- 21730843
TI  - Mechanisms and management of vision loss following orbital and facial trauma.
AB  - PURPOSE OF REVIEW: To examine the proposed mechanisms of vision-threatening
      injuries occurring secondary to orbital and facial trauma: traumatic optic
      neuropathy (TON), retrobulbar haemorrhage (RBH) and penetrating eye injury. To
      evaluate the evidence supporting different management options for traumatic
      vision-threatening injury. RECENT FINDINGS: Despite considerable debate over the
      roles of surgical decompression and systemic steroid therapy for TON, these
      interventions have not been proved to be more effective than conservative
      management and there is limited evidence that the use of steroids may be
      associated with an adverse outcome. Lateral canthotomy and inferior cantholysis
      have been proven to be effective treatments for RBH. Orbital exploration and
      surgical evacuation of haematoma remains a second line intervention. Open globe
      injuries require immediate primary surgical exploration and repair. Irretrievable
      devastating globe injuries require either enucleation or evisceration. There is
      no consensus as to which is the best treatment with recent surveys indicating
      that enucleation is preferred in the USA and evisceration in the United Kingdom.
      SUMMARY: Conservative management is the first line treatment for TON. The
      evidence strongly supports lateral canthotomy and inferior cantholysis as best
      treatment for RBH. There is no consensus as to whether enucleation or
      evisceration is the best treatment for irretrievable devastating globe injury.
      The choice of management is currently determined by surgeon preference.

PMID- 21730844
TI  - Orbital implants for fracture repair.
AB  - PURPOSE OF REVIEW: To review the latest advancements in implant materials for
      orbital fracture repair, including analysis of the last year in research. RECENT
      FINDINGS: Advances in the manufacture of highly biocompatible alloplastic
      materials offer an alternative to traditional autologous implants for orbital
      fracture repair. The emergence of the composite implant offers the stability and
      strength of traditional titanium mesh, while the porous polyethylene shell allows
      for greater fibrovascular integration and a potential for decreased risk of
      postoperative complications. Development of copolymers and biomechanical
      constructs for the delivery of bone stimulating proteins and stem cells serve to
      restore orbital volume after fracture repair through stimulation of the patient's
      own tissue. These recent developments are promising; however, their safety and
      efficacy have not been verified in humans. SUMMARY: The appropriate choice of
      orbital implant for fracture repair ensures appropriate orbital reconstruction in
      an effort to alleviate diplopia, enophthalmos, orbital dystopia, and extraocular
      muscle restriction.

PMID- 21730845
TI  - Taking the family history in genetic disease: a guide for ophthalmologists.
AB  - PURPOSE OF REVIEW: The family pedigree is an important tool in the field of
      ophthalmology. Recent advances in genetic testing for ophthalmic conditions
      underlie the need to offer genetic testing to patients when appropriate. Future
      availability of gene therapy for some ocular diseases further illustrates the
      importance of gene testing for patients seen in the ophthalmology clinic. RECENT
      FINDINGS: The pedigree is the first step in the genetic screening process and can
      guide the clinician in determining the likely genetic cause of a given disorder.
      Although not every patient warrants generating a pedigree, for patients whose
      condition may have a heritable basis, it is worthwhile to document the family
      history for several reasons. The pedigree gives us information about the mode of
      inheritance and can give clues toward a diagnosis. We can also determine whether
      family members are at risk for developing disease and calculate the recurrence
      risk for future offspring. The pedigree can help differentiate between a syndrome
      and an isolated ocular disease and may indicate the need for a specialist
      referral if there is risk of other systemic abnormalities. The pedigree gives us
      important information that may guide us in deciding which genes to test for and
      allows us to counsel the family appropriately. SUMMARY: The purpose of this
      review is to inform ophthalmologists on how to take a detailed family history
      relevant to possible genetic disorders, outline the information that can be
      obtained from the family history, and describe how this information can be used
      to optimize patient care.

PMID- 21730846
TI  - Mitochondrial disorders and the eye.
AB  - PURPOSE OF REVIEW: Mitochondrial disease is a heterogeneous group of energy
      metabolism disorders that present across all ages with a wide range of ocular or
      multisystemic manifestations. This review focuses on recent progress made toward
      understanding the various ophthalmologic manifestations of primary mitochondrial
      diseases and discusses the implications of mitochondrial dysfunction, placing
      particular emphasis on recent investigations into the pathogenesis and emerging
      therapies for mitochondrial-based ophthalmologic disorders. RECENT FINDINGS:
      Novel pathogenic mitochondrial DNA mutations continue to be detected in diverse
      ethnic populations for primary mitochondrial ophthalmologic disorders that
      commonly affect the optic nerve, retina, and extraocular muscles. Promising
      antioxidant and gene therapy approaches are being actively investigated to treat
      these ophthalmologic manifestations, as in Leber's hereditary optic neuropathy.
      Mitochondrial dysfunction is also increasingly implicated in common
      ophthalmologic disorders of aging, including diabetic retinopathy, age-related
      macular degeneration, and glaucoma. Several proteins recently recognized to play
      a role in the mitochondrial oxidative stress response within retinal cells, such
      as prohibitin and MMP2, may serve as novel biomarkers and therapeutic targets for
      common ophthalmologic disorders. Therapies that inhibit mitochondrial function
      and induce apoptosis within tumor cells, such as EDL-155 and curcumin, may offer
      novel therapeutic agents for ocular neoplasms such as retinoblastoma and uveal
      melanoma. SUMMARY: Primary mitochondrial genetic disease manifestations can
      involve almost all aspects of the eye. Mitochondrial dysfunction is increasingly
      recognized as playing a causative role in the common ophthalmologic disorders in
      aging. This understanding has unleashed a range of emerging therapeutic
      approaches for mitochondrial-based ophthalmologic disorders directed at
      optimizing mitochondrial function.

PMID- 21730848
TI  - Genetics of primary glaucoma.
AB  - PURPOSE OF REVIEW: To provide an overview of the genetics of the primary open
      angle glaucomas with particular attention to congenital, infantile, and juvenile
      forms. RECENT FINDINGS: Mutations in CYP1B1, in addition to being the most common
      identifiable cause of autosomal recessive primary congenital/infantile glaucoma,
      can infrequently underlie juvenile and even primary adult-onset open-angle
      glaucoma, particularly in certain consanguineous populations. In 2009, patients
      diagnosed with congenital/infantile glaucoma were found to have recessive
      mutations in a second gene, LTBP2, with a phenotypic spectrum that includes
      primary megalocornea, spherophakia with ectopia lentis, and lens-related
      glaucoma. The most common identifiable cause of primary juvenile open-angle
      glaucoma across most populations remains heterozygous (autosomal dominant) MYOC
      mutation, underlying up to one-third of cases and possibly sometimes involved in
      earlier and later onset glaucomas Although primary adult-onset open-angle
      glaucoma usually does not follow simple Mendelian genetics and is etiologically
      complex, genome-wide association studies are uncovering genetic susceptibility
      factors. In some cases, primary adult-onset open-angle glaucoma can be caused by
      heterozygous mutation in MYOC, OPTN, or WDR36. In addition, in 2009, heterozygous
      NTF4 mutation was associated with the phenotype in a small percentage of patients
      from a German cohort. SUMMARY: Seemingly unaffected siblings of children with
      CYP1B1-related primary congenital/infantile glaucoma should undergo genetic
      testing because of variable expressivity for the phenotype; such testing should
      also be considered for other asymptomatic relatives, especially in consanguineous
      families. In western populations, dominant MYOC mutation remains a common cause
      of primary open-angle juvenile glaucoma and infrequently can be implicated in
      congenital/infantile or adult-onset forms; identified families should undergo
      genetic counseling. Primary adult-onset open-angle glaucoma rarely follows simple
      Mendelian genetics, but genomic studies in different populations are revealing
      potential genetic risk factors for the phenotype.

PMID- 21730847
TI  - Genetics of anterior segment dysgenesis disorders.
AB  - PURPOSE OF REVIEW: Anterior segment dysgenesis (ASD) disorders encompass a
      spectrum of developmental conditions affecting the cornea, iris, and lens and are
      generally associated with an approximate 50% risk for glaucoma. These conditions
      are characterized by both autosomal dominant and recessive patterns of
      inheritance often with incomplete penetrance/variable expressivity. This article
      summarizes what is known about the genetics of ASD disorders and reviews recent
      developments. RECENT FINDINGS: Mutations in Collagen type IV alpha-1 (COL4A1) and
      Beta-1,3-galactosyltransferase-like (B3GALTL) have been reported in ASD patients.
      Novel findings in other well known ocular genes are also presented, among which
      regulatory region deletions in PAX6 and PITX2 are most notable. SUMMARY: Although
      a number of genetic causes have been identified, many ASD conditions are still
      awaiting genetic elucidation. The majority of characterized ASD genes encode
      transcription factors; several other genes represent extracellular matrix-related
      proteins. All of the involved genes play active roles in ocular development and
      demonstrate conserved functions across species. The use of novel technologies,
      such as whole genome sequencing/comparative genomic hybridization, is likely to
      broaden the mutation spectrums in known genes and assist in the identification of
      novel causative genes as well as modifiers explaining the phenotypic variability
      of ASD conditions.

PMID- 21730849
TI  - Macular cysts in retinal dystrophy.
AB  - PURPOSE OF REVIEW: To describe the entity of macular cysts in retinal dystrophy,
      differentiate it from cystoid macular edema (CME), and review the role of
      carbonic anhydrase inhibitors in management. RECENT FINDINGS: Macular cysts in
      retinal dystrophy are seen in retinopathies caused by mutations in the NR2E3
      gene, juvenile X-linked retinoschisis (XLRS), and some other retinal dystrophies.
      These must be distinguished from CME. Optical coherence tomography can clearly
      demonstrate intraretinal cysts which may not be clinically detectable.
      Intravenous fluorescein angiography (IVFA) does not show macular
      hyperfluorescence (i.e. leakage). Molecular genetic testing aids in the diagnosis
      and elucidation of pathophysiology. Carbonic anhydrase inhibitors may promote
      resolution of the cysts resulting in visual improvement. SUMMARY: Non-CME macular
      cysts in retinal dystrophies can be differentiated from CME by a combination of
      clinical examination, IVFA, and molecular genetic testing to identify causative
      phenotype. Carbonic anhydrase inhibitors may be effective in promoting
      resolution.

PMID- 21730850
TI  - The prognostic value of hematological and systemic inflammatory disorders in
      invasive bladder cancer.
AB  - PURPOSE OF REVIEW: In contrast to the large amount of evidence reporting on the
      oncological significance of various clinicopathological and molecular parameters
      for survival in invasive bladder cancer, alterations of preoperative
      hematological and systemic inflammatory parameters have not been sufficiently
      addressed in the literature so far. RECENT FINDINGS: Pretreatment serum C
      reactive protein was recently incorporated in a new outcome prediction model,
      termed Tumor Node Resection C-reactive protein score, and demonstrated a
      significant increase in the predictive accuracy of standard pathologic risk
      factors for cancer-specific survival after radical cystectomy. The presence of
      preoperative thrombocytosis is associated with multiple hematologic disorders in
      invasive bladder cancer and higher tumor aggressiveness suggesting that platelets
      play a role in tumor growth and metastasis formation. In patients undergoing
      second-line chemotherapy for metastatic disease, pretreatment lower hemoglobin
      level was identified as an independent prognostic factor for overall survival.
      SUMMARY: The degree of systemic inflammation and hematological disorders in
      invasive bladder cancer is often associated with more aggressive disease. The
      incorporation of hemoglobin levels, serum C-reactive protein and platelet counts
      into current nomograms might improve significantly the predictive accuracy of
      standard clinicopathological risk factors and provide improved prognostication
      for counseling more selectively the use of chemotherapy in the neoadjuvant,
      adjuvant and metastatic setting.

PMID- 21730851
TI  - Oncological outcomes of partial nephrectomy for renal carcinoma greater than 4
      cm.
AB  - PURPOSE OF REVIEW: To provide the clinical evidence and benefits of performing
      partial nephrectomy for renal tumors greater than 4 cm. RECENT FINDINGS: Partial
      nephrectomy was historically performed only for the essential indications of a
      tumor in a functional or anatomical solitary kidney or in the face of bilateral
      renal tumors. Partial nephrectomy has now emerged as an oncologically equivalent
      operation to radical nephrectomy for T1a tumors (<4 cm) with the added benefit of
      renal functional preservation which can prevent or delay the onset of chronic
      kidney disease (CKD). CKD is an independent risk factor for hospitalization
      events, cardiovascular disease, and worse overall survival. Recent evidence has
      demonstrated that partial nephrectomy also provides equivalent oncological
      results for larger renal tumors including those of 4-7 cm and even for greater
      than 7 cm, whenever technically feasible with the continued added benefit of
      renal functional preservation. Partial nephrectomy is effectively performed using
      both open surgical techniques and increasingly by minimally invasive approaches
      although the latter is technically challenging. SUMMARY: Despite the mounting
      clinical evidence that partial nephrectomy is an effective and preferable
      approach to the T1 renal mass, it remains markedly underutilized in the USA and
      abroad. The overzealous use of radical nephrectomy for the T1 renal mass, by
      whatever surgical approach, must now be considered detrimental to the long-term
      health of the kidney tumor patient.

PMID- 21730852
TI  - Kidneys from patients with small renal tumours used for transplantation: outcomes
      and results.
AB  - PURPOSE OF REVIEW: To increase the number of patients who could benefit from
      renal transplantation new strategies need to be considered. The potential utility
      of kidneys found to contain small renal tumours has been proposed and is
      reviewed. RECENT FINDINGS: Successful outcomes have been observed using kidneys
      from deceased and live donors following excision of small incidentally detected
      renal cell carcinoma (RCC). In patients electing radical nephrectomy for small
      renal masses, the kidney, following excision of the tumour can be used as a novel
      form of altruistic organ donation. With these donor sources, the risk of tumour
      recurrence is extremely low with patient survival significantly better than the
      alternative of long-term dialysis and graft outcomes similar to other sources of
      donor organs. SUMMARY: Although controversial, the presence of a small renal
      tumour should not prevent transplantation of a kidney from either deceased or
      potential live donors. In circumstances, where patients elect for radical
      nephrectomy for small tumours, these kidneys should be considered for patients
      who may not otherwise have the opportunity of renal transplantation.

PMID- 21730853
TI  - Renal functional outcomes after surgery for renal cortical tumors.
AB  - PURPOSE OF REVIEW: To review the established literature on renal functional
      outcomes and related pathologies after surgery for renal cortical tumors. RECENT
      FINDINGS: Recent data support the prevailing notion that radical nephrectomy is
      associated with higher rates of chronic kidney disease, regardless of the metric
      used in determining renal function. Furthermore, higher rates of chronic kidney
      disease in patients receiving radical nephrectomy have been associated with more
      noncancer deaths and higher rates of cardiovascular mortality. SUMMARY: Patients
      undergoing radical nephrectomy are at an increased risk of noncancer mortality,
      and in some cases, cardiovascular events and death. A comprehensive preoperative
      risk assessment is paramount in managing newly diagnosed patients with small
      renal masses.

PMID- 21730854
TI  - BMI and the risk of renal cell carcinoma.
AB  - PURPOSE OF REVIEW: Incidence of obesity and renal cell carcinoma (RCC) are
      increasing, and RCC remains a lethal disease if not identified at an early stage.
      There is an increasing body of evidence linking obesity to the risk of developing
      RCC. RECENT FINDINGS: There is a wealth of epidemiological evidence supporting a
      higher risk of developing RCC in obese individuals, and in a dose-response
      manner. This is particularly pertinent in the development of the clear cell
      subtype (ccRCC), in which there appears to be a special interplay between ccRCC,
      obesity and von Hippel-Lindau (VHL) gene defects, driving the
      proangiogenic/proliferative pathway as a result of metabolites produced by
      adipose tissue, the epigenetic silencing of a tumour suppressor in close
      proximity to the VHL gene, hypoxia, obesity-related hypertension, lipid
      peroxidation and increased insulin-like growth factor-1. SUMMARY: Obesity-related
      diseases, including cancers, are increasing. There are many complex biomolecular
      pathways interacting in obesity, especially in ccRCC in which there appears to be
      a specific interplay in VHL mutations.

PMID- 21730855
TI  - Renal cell carcinoma of native kidneys in renal transplant patients.
AB  - PURPOSE OF REVIEW: To outline recent findings on renal cell carcinoma (RCC) of
      native kidneys in renal transplant patients. RECENT FINDINGS: The incidence of
      RCC in native kidneys of renal transplant patients varies between 0.3 and 4.8%.
      The risk is increased in patients with acquired cystic kidney disease, in men,
      African-Americans, recipients aged at least 65 years, those with a longer
      pretransplant dialysis interval, a donor aged at least 50 years, and microscopic
      hematuria. On the basis of the risk factor profile, periodic ultrasound screening
      is recommended. Most RCCs in renal transplant patients are incidental low-stage,
      low-grade tumors with a good prognosis. The outstanding pathological findings are
      bilateral occurrence, papillary subtype and multifocality. Minimally invasive
      radical nephrectomy can be performed safely in these patients. Systemic treatment
      of metastatic RCC represents a challenge, with rapamycin analogues being an
      attractive option. SUMMARY: The risk for RCC in native kidneys after renal
      transplantation is substantial. Multiple risk factors have been identified,
      although the exact risk-factor dependent screening protocol has yet to be
      determined. Most RCCs in renal transplant patients are low-stage, low-grade
      tumors with a good prognosis.

PMID- 21730856
TI  - High magnification cystoscopy in the primary diagnosis of bladder tumors.
AB  - PURPOSE OF REVIEW: In bladder cancer, discrimination between benign and malignant
      tissue may remain tricky with current endoscopic tools. On the basis of our
      recent experience with high-magnification cystoscopy, compared with other tools
      such as optical coherence tomography or confocal laser endomicroscopy, it is
      suggested here that this discrimination may well be feasible endoscopically. The
      clinical potential of these systems that are being developed as complementary
      tools to the current endoscopic equipment is reviewed. RECENT FINDINGS: At
      present, white-light cystoscopy, either assisted by fluorescence cystoscopy or
      narrow-band imaging, is proposed for the global cystoscopic examination of
      bladder cancer patients. Both techniques compete to help to reduce the recurrence
      rate by improving exophytic tumor detection, and the extent of carcinoma in situ
      and high-grade dysplasia. All of which are important prognosis factors for
      disease progression. In addition, recent findings on neoangiogenesis that
      accompanies early stage bladder cancer show that this may also be an important
      observable switch in bladder cancerogenesis, as it is found very early in tumor
      development. The high magnification cystoscopy as a complementary tool to
      fluorescence cystoscopy allows classification of the vessel patterns on
      fluorescence positive sites, and thus facilitates the discrimination between
      cancerous and noncancerous lesions. This information may be useful to reduce the
      false positive rate of fluorescence cystoscopy. SUMMARY: Emerging technologies
      aiming at a real-time in-situ discrimination between benign and malignant tissue
      during endoscopic bladder exploration is a promising development for the
      monitoring of bladder cancer patients.

PMID- 21730857
TI  - The placebo effect and the influence of participant expectation on hearing aid
      trials.
AB  - OBJECTIVE: The aim of the study was to investigate the influence of participant
      expectation on the outcome of a trial that compared two behind-the-ear hearing
      aids with identical electroacoustic performance, except that one was called a
      "new" hearing aid and the other a "conventional" hearing aid. DESIGN: Twenty
      experienced adult hearing aid users were told that they were taking part in a
      trial that compared new and conventional hearing aid technology. They attended a
      single test session where they were fitted with each hearing aid, in a balanced
      design, set to the same National Acoustic Laboratories' nonlinear fitting
      procedure (Version 1) prescription target for a typical age-related hearing
      impairment. Outcome measures were selected to be representative of hearing aids
      trials and included (i) the Four Alternative Auditory Feature test (presented at
      65 dB (A) and SNR ratio of +2 dB), (ii) sound quality ratings for six different
      sound samples (a selection of speech, music, and environmental sounds), and (iii)
      overall personal preference. RESULTS: There was marginally better mean
      performance with the new hearing aid on the Four Alternative Auditory Feature
      test (M = 62.3%, SD = 10.4 versus M = 60.7%, SD = 9.0; z = -1.84, p = 0.03, one
      tailed, effect size Pearson's r = 0.08; although p = 0.06, two-tailed). The new
      hearing aid was also consistently rated more highly on all sound quality ratings
      and this difference was statistically significant (M = 9.12, SD = 1.02 versus M =
      8.35, SD 1.17; z = -2.88, p < 0.01, two-tailed, r = 0.33). Fifteen (75%)
      participants expressed an overall personal preference for the new hearing aid
      with the remainder expressing no preference (p = 0.02, r = 0.50). CONCLUSIONS:
      These results suggest a need to control for placebo effects in hearing aid trials
      and to interpret cautiously any hearing aid trial that did not control for this
      effect.

PMID- 21730858
TI  - Preliminary results of the relationship between the binaural interaction
      component of the electrically evoked auditory brainstem response and interaural
      pitch comparisons in bilateral cochlear implant recipients.
AB  - OBJECTIVE: : The purpose of this study was to investigate the relationship
      between electrophysiologic measures of the binaural interaction component (BIC)
      of the electrically evoked auditory brainstem response and psychophysical
      measures of interaural pitch comparisons in Nucleus bilateral cochlear implant
      users. DESIGN: : Data were collected for 10 postlingually deafened adult cochlear
      implant users. Each subject conducted an interaural pitch-comparison task using a
      biphasic pulse train with a pulse rate of 1000 pulses per second (pps) at high
      stimulation levels. Stimuli were presented in a two-interval, two-alternative
      forced-choice procedure with roving current variations. A subgroup of four
      subjects repeated the task at low stimulation levels. BICs were measured using
      loudness balanced, biphasic current pulses presented at a rate of 19.9 pps for
      each subject by pairing the electrode 12 (out of 22 intracochlear electrodes) in
      the right ear with each of 11 electrodes spaced across the electrode array in the
      left ear. The BIC was measured at high stimulation levels in 10 subjects and at
      low stimulation levels in 7 subjects. Because of differences in stimulation rate
      used in BIC measures and interaural pitch comparisons, the actual stimulation
      levels were different in these two measures. The relationship between BIC
      responses and results of interaural pitch comparisons was evaluated for each of
      the individual subjects and at the group level. Evaluation was carried out
      separately for results obtained at high and low stimulation levels. RESULTS: :
      There was no significant correlation between results of BIC measures and
      interaural pitch comparisons on either the individual or group levels. Lower
      stimulation level did not improve the relationship between these two measures.
      CONCLUSIONS: : No significant correlations between psychophysical measures of
      interaural pitch comparisons and electrophysiologic measures of the BIC of the
      electrically evoked auditory brainstem response were found. The lack of
      correlation may be attributed to methods used to quantify the data, small number
      of subjects retested at low stimulation levels, and central processing components
      involved in the interaural pitch-comparison task.

PMID- 21730859
TI  - A neural basis of speech-in-noise perception in older adults.
AB  - OBJECTIVE: We investigated a neural basis of speech-in-noise perception in older
      adults. Hearing loss, the third most common chronic condition in older adults, is
      most often manifested by difficulty understanding speech in background noise.
      This trouble with understanding speech in noise, which occurs even in individuals
      who have normal-hearing thresholds, may arise, in part, from age-related declines
      in central auditory processing of the temporal and spectral components of speech.
      We hypothesized that older adults with poorer speech-in-noise (SIN) perception
      demonstrate impairments in the subcortical representation of speech. DESIGN: In
      all participants (28 adults, age 60-73 yr), average hearing thresholds calculated
      from 500 to 4000 Hz were <= 25 dB HL. The participants were evaluated
      behaviorally with the Hearing in Noise Test (HINT) and neurophysiologically using
      speech-evoked auditory brainstem responses recorded in quiet and in background
      noise. The participants were divided based on their HINT scores into top and
      bottom performing groups that were matched for audiometric thresholds and
      intelligent quotient. We compared brainstem responses in the two groups,
      specifically, the average spectral magnitudes of the neural response and the
      degree to which background noise affected response morphology. RESULTS: In the
      quiet condition, the bottom SIN group had reduced neural representation of the
      fundamental frequency of the speech stimulus and an overall reduction in response
      magnitude. In the noise condition, the bottom SIN group demonstrated greater
      disruption in noise, reflecting reduction in neural synchrony. The role of
      brainstem timing is particularly evident in the strong relationship between SIN
      perception and quiet-to-noise response correlations. All physiologic measures
      correlated with SIN perception. CONCLUSION: Adults in the bottom SIN group
      differed from the audiometrically matched top SIN group in how speech was
      neurally encoded. The strength of subcortical encoding of the fundamental
      frequency appears to be a factor in successful speech-in-noise perception in
      older adults. Given the limitations of amplification, our results suggest the
      need for inclusion of auditory training to strengthen central auditory processing
      in older adults with SIN perception difficulties.

PMID- 21730860
TI  - The effect of gabapentin on gap detection and forward masking in young and old
      gerbils.
AB  - OBJECTIVES: Auditory temporal processing frequently appears more affected in old
      subjects than would be predicted by the degree of peripheral hearing loss,
      pointing to an age-dependent central processing deficit. In parallel, an age
      dependent decline of inhibitory function has been demonstrated in the auditory
      pathway, suggesting a causal relationship between temporal processing and
      inhibition. Gabapentin has been specifically synthesized as a potential gamma
      amino-butyric-acid (GABA) mimetic with the capability to cross the blood-brain
      barrier. Gabapentin treatment ameliorated tinnitus in a rat model and improved
      tinnitus annoyance in humans with acoustic trauma. Consequently, the present
      study evaluated the effect of gabapentin on auditory temporal processing in the
      gerbil model. DESIGN: Psychometric functions were collected for different test
      paradigms. (A) "Gap detection": The detection of a gap in the middle of a 800
      msec broadband noise pulse was determined either at 15 or at 30 dB SL. (B)
      "Forward masking": The detection of a 20 msec probe stimulus following 2.5 msec
      after a 400 msec 40 dB SPL masker was determined with masker and probe frequency
      at 2.85 kHz. The effect of gabapentin was evaluated by collecting gap detection
      and forward masking functions before, during, and after treating gerbils with
      gabapentin doses of 115 or 350 mg/kg/day administered via drinking water. Data
      under different experimental conditions were collected for groups of 3 to 5 young
      (<2 years) and 6 to 10 old (>2 years) gerbils. Two-way analyses of variance for
      the factors age groups and treatment groups with subsequent pairwise comparisons
      for significant effects were used for the statistical evaluation of the data.
      RESULTS: For gap detection, mean thresholds were significantly increased in the
      group of old as compared with the young gerbils at 30 dB SL (young 2.0 msec; old
      3.2 msec) and at 15 dB SL (young 2.9 msec; old 9.1 msec). Gabapentin had no
      significant effect on gap detection, and there was no significant interaction
      between age group and gabapentin treatment. Mean thresholds in the forward
      masking paradigm were significantly elevated in old (45.5 dB SPL) as compared
      with young (35.0 dB SPL) gerbils. Overall, gabapentin had no significant effect
      on masked thresholds; however, there was a significant interaction between
      treatment and age. Subsequent pairwise comparisons revealed no significant effect
      on masked thresholds in old gerbils but showed significantly elevated thresholds
      of young gerbils during 350 mg/kg gabapentin (38.3 dB SPL) compared with
      thresholds obtained in young gerbils before (32.3 dB SPL) and after (33.5 dB SPL)
      treatment. CONCLUSIONS: Gabapentin did not exert a therapeutic effect on impaired
      gap detection and forward masking in old gerbils. The lack of an effect of
      gabapentin on impaired auditory temporal processing in old gerbils and the
      finding of elevated masked thresholds in young gerbils can be reconciled with
      reports of only moderate GABAergic effects compared with other drugs (e.g.,
      comparing elevation of GABA levels in the brain by gabapentin and vigabatrin) and
      effects due to binding of gabapentin to alpha-2-delta units of voltage-gated
      calcium channels.

PMID- 21730861
TI  - Sperm counts, data responsibility, and good scientific practice.

PMID- 21730862
TI  - Short-term impact of ambient air pollution and air temperature on blood pressure
      among pregnant women.
AB  - BACKGROUND: Epidemiologic studies have reported inconsistent findings for the
      association between air pollution levels and blood pressure (BP), which has been
      studied mainly in elderly subjects. Short-term air pollution effects on BP have
      not been investigated in pregnant women, who may constitute a vulnerable
      population. METHODS: Between 2002 and 2006, 1500 pregnant women from a mother
      child cohort study conducted in Nancy and Poitiers, France, underwent 11,220
      repeated BP measurements (average, 7.5 measurements/woman). Nitrogen dioxide
      (NO2), particulate matter with an aerodynamic diameter below 10 MUm (PM10), and
      meteorologic variables were measured on an hourly basis at permanent monitoring
      sites. We studied changes of BP in relation to short-term variations of air
      pollution and temperature with mixed models adjusted for meteorologic and
      personal characteristics. RESULTS: A 10 degrees C decrease in temperature led to
      an increase in systolic BP of 0.5% (95% confidence interval = 0.1% to 1.0%).
      Elevated NO2-levels 1 day, 5 days and averaged over 7 days before the BP
      measurement were associated with reduced systolic BP. The strongest decrease was
      observed for the 7-day NO2 average (-0.4% [-0.7% to -0.2%] change for an 11
      MUg/m3 increase in NO2). PM10 effects on systolic BP differed according to
      pregnancy trimester: PM10 concentration was associated with systolic BP increases
      during the first trimester and systolic BP decreases later in pregnancy.
      CONCLUSIONS: We observed short-term associations of air pollution and of
      temperature with BP in pregnant women. Whether such changes in BP have clinical
      implications remains to be investigated.

PMID- 21730863
TI  - Children with anterior mediastinal mass:  procedural sedation with
      dexmedetomidine.

PMID- 21730864
TI  - Nasotracheal intubation with the McGrath videolaryngoscope in patients with
      difficult airway.

PMID- 21730865
TI  - Cerebral oxygen desaturation during beach chair position.
AB  - CONTEXT: Cases of ischaemic brain damage have been reported in relatively healthy
      patients undergoing shoulder surgery in the beach chair position. Unrecognised
      cerebral hypoperfusion may have contributed to these catastrophic events,
      indicating that routine anaesthesia monitoring may not suffice. Near-infrared
      spectroscopy (NIRS) provides a non-invasive, continuous method to measure
      regional cerebral oxygen saturation (rScO2). OBJECTIVES: The aim of this clinical
      investigation was to evaluate the prevalence of regional cerebral oxygen
      desaturation in patients undergoing shoulder surgery in the upright position
      during routine anaesthesia management. We also aimed to identify some causal
      factors for cerebral desaturation. DESIGN: Prospective, observational, blinded
      study. SETTING: University hospital. Observation period from 19 05 2008 to 26 08
      2008. PATIENTS: Twenty consecutive adult patients presenting for elective
      shoulder surgery under general anaesthesia in the beach chair position were
      enrolled. Patients with clinically apparent neurological or cognitive dysfunction
      were excluded. INTERVENTIONS: Routine anaesthesia management and standard
      monitoring were used. The responsible anaesthesiologist was blinded to the rScO2
      data and was not informed about the purpose of the study. MAIN OUTCOME MEASURES:
      The prevalence of cerebral oxygen desaturation was measured. RESULTS: With beach
      chair positioning, rScO2 decreased significantly from 79+/- to 57+/-9% on the
      left side and from 77+/-10 to 59+/-10% on the right side (P<0.001). A relative
      decrease in rScO2 of more than 20% occurred in 80% of patients when the beach
      chair position was adopted. Postural decreases in cerebral oxygenation were
      related to blood pressure (r=0.60, P=0.007) and end-tidal carbon dioxide
      concentration (r=0.47, P=0.035). CONCLUSION: The high prevalence of significant
      cerebral oxygen desaturation during shoulder surgery in the upright position
      underlines the need for close monitoring. NIRS might constitute a valuable
      technique to detect cerebral hypoperfusion in this high-risk group of patients.

PMID- 21730866
TI  - Management of the nontraumatic hot swollen joint.
AB  - AIM: To audit the management of nontraumatic hot swollen joints presenting to a
      large UK university teaching hospital and to design a simple emergency department
      (ED) algorithm to improve patient care based on existing guidelines and our
      experience. METHODS: Prospective audit. RESULTS: Between 2 February and 8 May
      2009, 77 patients were enrolled. Median age was 58 years (range 19-89 years) and
      57% were male patients. The most commonly affected joint was the knee (38%), with
      the knee, wrist, ankle, hip and elbow comprising 87% of affected joints. Thirty
      three (43%) joints were aspirated; no organisms were found on microscopy or
      cultured in any aspirates; crystals were found in eight aspirates. Twenty-four
      patients were admitted. Gout was the most common final diagnosis in 14 (18%)
      patients, with cellulitis being the next most common diagnosis (n=9; 12%).
      Bursitis (n=7; 9%), nonspecific arthritis (n=7; 9%) and reactive arthritis (n=6;
      8%) were also not uncommon. Four (5%) patients were treated for possible septic
      arthritis. It was noticed that many patients spent a long time in the ED waiting
      firstly for a decision to aspirate, and secondly for a senior clinician to
      perform this. CONCLUSION: Patients presenting with nontraumatic hot swollen
      joints are common and the knee, wrist, ankle, hip and elbow are commonly
      affected. Joint aspirate is required to rule out septic arthritis, should be
      considered early and appropriate personnel called, and can show the presence of
      gout or pseudogout. Septic arthritis should still be considered in patients with
      a negative aspirate in whom there is high clinical suspicion. Our simple ED
      algorithm may improve patient care.

PMID- 21730867
TI  - Identifying adult asthmatic patients with an abnormal chest radiograph in the
      emergency department.
AB  - OBJECTIVES: The Global Initiative for Asthma (GINA) guidelines classify asthmatic
      exacerbations into mild, moderate, severe episodes and those with imminent
      respiratory arrest. We aimed to identify proportions of adult asthmatic patients
      in different subgroups with abnormal chest radiograph (CR) results and to explore
      predictors of them. METHODS: In this prospective study, we recruited consecutive
      adult patients with asthmatic exacerbation over 7 months. Primary outcomes were
      rates of abnormal CR results among the subgroups. Secondary outcomes included
      predictors of CR abnormalities, rates of disposition status, and their
      distribution of abnormal CR results. Logistic regression was applied to identify
      predictors of an abnormal CR result. RESULTS: We recruited 201 patients; CR was
      carried out in 84.6%. Rates of abnormal CR results were 8.1% (nine of 111), 17.6%
      (nine of 51), 20% (one of five), and 0% (zero of three) in the mild, moderate,
      severe, and imminent respiratory arrest subgroups. No statistically significant
      differences existed when the rate of CR abnormalities in each subgroup was
      compared with the combined rate of the other three subgroups (P values: 0.186
      0.943). There were 92 (45.8%) planned discharges, 14 (7%) discharges against
      medical advice, and 95 (47.2%) admissions. The rates of abnormal CR results in
      the planned discharged group versus the rest (discharges against medical advice+
      admissions) were 3% (two of 67) versus 16.5% (17 of 103) (P=0.006). Logistic
      regression revealed the female sex to be associated with an abnormal CR result
      [odds ratio 10.1 (95% confidence interval: 2.2-45.8)]. CONCLUSION: Abnormal CR
      results were infrequent in mild exacerbations and planned discharged patients.
      The female sex was the only predictor of an abnormal CR result.

PMID- 21730868
TI  - Improving the efficiency of the emergency general surgical service.
AB  - OBJECTIVE: To improve the quality and efficiency of our emergency surgical
      service. METHODS: Until 2007, the surgical on-call in our unit was run on a
      'consultant of the day' model with triage in a 10-bed surgical receiving unit
      (SRU) before admission to the wards. The reduction in junior doctors' hours meant
      little continuity and delays in care.In July 2007, the SRU was expanded and a
      daily on-ward ultrasound session was established. The consultant rota was changed
      to a split-week model with twice-daily SRU ward rounds, allowing unstable
      patients regular senior assessment. RESULTS: As a result of the change, our acute
      length of stay reduced from 4.4 to 3.8 days and our actual versus expected length
      of stay was the best figure country-wide. CONCLUSION: Early consultant review and
      swift ultrasound assessment reduce admissions and patient stay. We have combined
      these factors in our emergency service and have delivered significant cost
      savings and improved care.

PMID- 21730869
TI  - Prognostic significance of serum gamma-glutamyl transferase in patients with
      intermediate hepatocellular carcinoma treated with transcatheter arterial
      chemoembolization.
AB  - OBJECTIVES: Not every unresectable hepatocellular carcinoma (HCC) could receive
      survival benefits from transcatheter arterial chemoembolization (TACE), even for
      intermediate HCC (Barcelona Clinic Liver Cancer stage B). The aim of this study
      was to investigate prognostic significance of serum gamma-glutamyl transferase
      (GGT) in patients with intermediate HCC treated with TACE. METHODS: A total of
      277 patients with intermediate HCC were consecutively treated with TACE and
      overall survival (OS) was evaluated with the Kaplan-Meier method. Significant
      difference was estimated with the Log rank method according to GGT value before
      treatment. Univariate and multivariate analyses were used for the study of
      significance of prognostic factor. RESULTS: The median follow-up period was 18.7
      months. The 1-year and 3-year OS rates were 71.6 and 38.5% in patients with
      normal GGT and 48.8 and 16.9% in patients with high GGT (P=0.002). High GGT,
      correlating with higher tumor size, alpha-fetoprotein (AFP), and alanine
      aminotrasferase, was an independent prognostic factor for OS (P=0.009). Others
      included tumor size and ascites. Furthermore, in small HCC and normal AFP
      subgroup, serum GGT was also correlated with OS (P=0.013 and 0.041,
      respectively). The combination of GGT and AFP had a better power to predict the
      TACE effects. CONCLUSION: GGT level was an important prognostic factor to predict
      prognosis of patients with intermediate HCC treated with TACE.

PMID- 21730870
TI  - Effects of endoscopic papillary balloon dilation and endoscopic sphincterotomy on
      bacterial contamination of the biliary tract.
AB  - BACKGROUND AND STUDY AIMS: Although endoscopic papillary balloon dilation (EPBD)
      has appeared with the expectation of better preserving sphincter of Oddi function
      than endoscopic sphincterotomy (EST), whether it can more effectively prevent
      bacterial contamination of the biliary tract than EST is controversial. To
      address this issue, we investigated the bacterial flora in the bile after the two
      procedures. PATIENTS AND METHODS: Eighty-six patients were alternately allocated
      to EPBD or EST. Blood-liver function tests, ultrasonography, and endoscopic
      retrograde cholangiopancreatography were performed 6 months and 2 years after
      EPBD or EST, and the bile was sampled for bacterial culture during endoscopic
      retrograde cholangiopancreatography. Bactobilia and late complications were
      prospectively compared between the two procedures. RESULTS: Overall, no
      significant difference was found in the incidence of bactobilia between EPBD and
      EST at the two examination points. Limiting stone diameter to 8 mm or less, there
      was a trend toward lower rate of bactobilia in the EPBD group 2 years later
      although the statistical significance disappeared after correction for multiple
      comparisons. The absence rate of late complications after EPBD was higher than
      that after EST, but there was no significant difference between the two
      procedures, both for the overall patients and for the patients with small stones.
      CONCLUSION: EPBD has a possibility of suppressing bacterial contamination of the
      biliary tract compared with EST in patients with small stones. A large, long-term
      follow-up, randomized, controlled trial is necessary to clarify whether this
      benefit of EPBD reduces late complications.

PMID- 21730871
TI  - Investigation of the longitudinal relaxation rate of blood after gadobenate
      dimeglumine administration: sequence optimization, dynamic acquisition, and
      clinical impact for contrast-enhanced MR angiography of the carotid arteries.
AB  - OBJECTIVES: To optimize the image acquisition parameters for improved steady
      state (SS) contrast-enhanced magnetic resonance angiography (CE-MRA) of the
      carotid arteries with gadobenate dimeglumine. MATERIALS AND METHODS: An inversion
      recovery fast low-angle shot (IR-FLASH) sequence for ultrafast determination of
      the longitudinal relaxation rate R1 was first optimized on phantoms and tested
      against a routine variable repetition time (TR) spin echo sequence used as
      reference standard. Different combinations of flip angle (FA, between 6 and 14
      degrees) and inversion time (between 134 and 9000 milliseconds) were evaluated to
      achieve the best trade off between speed and accuracy. The optimized sequence was
      thereafter used in vivo in 5 subjects to determine the time evolution of blood R1
      at 1.5 T after administration of gadobenate dimeglumine at 0.1 mmol/kg
      bodyweight. An optimal FA for angiographic measurement was thereafter derived
      from the Ernst equation based on experimental values of R1 previously determined
      in vivo. Finally, steady-state CE-MRA examinations were performed in 20 subjects
      to evaluate the improved contrast achieved after optimization of the FA for
      maximal blood signal enhancement. RESULTS: An ultrafast IR-FLASH sequence with a
      flip angle of 8 degrees and a properly defined set of inversion time values was
      shown to give in vitro R1 determinations that were in good agreement with those
      obtained using a routine, time consuming, variable-TR spin echo sequence. The use
      of this ultrafast IR-FLASH sequence in vivo allowed the blood signal behavior in
      the carotid arteries after gadobenate dimeglumine administration to be monitored.
      Using this sequence, the R1 decreased from 8.7+/-0.96 s-1 at 30 seconds after
      injection to 3.8+/-0.24 s-1 at 10 minutes after injection. Based on these data
      for R1, the optimal FA for SS CE-MRA was calculated to be 18 degrees for a
      gradient echo acquisition protocol with TR=7.5 milliseconds, when gadobenate
      dimeglumine is used. Significantly higher blood signal to noise ratio was
      achieved on SS images acquired using a three-dimensional spoiled gradient echo
      sequence with a FA of 18 degrees than on corresponding images acquired with a FA
      of 35 degrees as used typically for intravascular blood pool contrast agents
      (52.5+/-8.3 vs. 29.5+/-6.0; P<0.05, Mann-Whitney U test). CONCLUSION: Detailed
      experimental knowledge of the in vivo R1 behavior of blood after gadobenate
      dimeglumine injection and appropriate modification of the acquisition parameters
      enables improved signal intensity enhancement on steady-state CE-MRA of the
      carotid arteries.

PMID- 21730872
TI  - Automated attenuation-based tube potential selection for thoracoabdominal
      computed tomography angiography:  improved dose effectiveness.
AB  - PURPOSE: To introduce a novel algorithm of automated attenuation-based tube
      potential selection and to assess its impact on image quality and radiation dose
      of body computed tomography angiography (CTA). MATERIALS AND METHODS: In all, 40
      patients (mean age 71+/-11.8 years, body mass index (BMI) 25.7+/-3.8 kg/m2, range
      18.8-33.8 kg/m2) underwent 64-slice thoracoabdominal CTA (contrast material: 80
      mL, 5 mL/s) using an automated tube potential selection algorithm (CAREkV), which
      optimizes tube-potential (70-140 kV) and tube-current (138.8+/-18.6 effective
      mAs, range 106-177 mAs) based on the attenuation profile of the topogram and on
      the diagnostic task. Image quality was semiquantitatively assessed by 2 blinded
      and independent readers (scores 1: excellent to 5: nondiagnostic). Attenuation
      and noise were measured by another 2 blinded and independent readers. Contrast-to
      noise ratio was calculated. The CT dose index (CTDIvol) was recorded and compared
      with the estimated CTDIvol of a standard 120 kV protocol without using the
      algorithm in each patient. Selected tube potentials were correlated with BMI and
      attenuation of the topogram. RESULTS: Diagnostic image quality was obtained in
      all patients (excellent: 14; good: 21; moderate: 5; interreader agreement:
      kappa=0.78). Mean attenuation, noise, and contrast-to-noise ratio were 260.8+/
      63.5 Hounsfield units, 15.5+/-3.3 Hounsfield units, and 14+/-4.2, respectively,
      with good to excellent agreement between readers (r=0.50-0.99, P<0.01 each).
      Automated attenuation-based tube potential selection resulted in a kV-reduction
      from 120 to 100 kV in 23 patients and to 80 kV in 1 patient, whereas tube
      potential increased to 140 kV in 1 patient. Automatically selected tube potential
      showed a significant correlation with both BMI (r=0.427, P<0.05) and attenuation
      of the topogram (r=0.831, P<0.001). CTDIvol (7.95+/-2.6 mGy) was significantly
      lower when using the algorithm compared with the standard 120 kV protocol
      (10.59+/-1.8 mGy, P<0.001), corresponding to an overall dose reduction of 25.1%.
      CONCLUSION: Automated attenuation-based tube potential selection based on the
      attenuation profile of the topogram is feasible, provides a diagnostic image
      quality of body CTA, and reduces overall radiation dose by 25% as compared with a
      standard protocol with 120 kV.

PMID- 21730873
TI  - Cerebral perfusion in perinatal hypoxia and resuscitation assessed by
      transcranial contrast-enhanced ultrasound and 3 T MRI in newborn pigs.
AB  - OBJECTIVE: Cerebrovascular factors are crucially involved in the early injury
      after perinatal asphyxia. With magnetic resonance imaging (MRI) and
      ultrasonography (US), this study aimed to quantify microvascular perfusion
      changes due to hypoxia and resuscitation, by comparing contrast-enhanced
      ultrasound (CEUS) to dynamic susceptibility contrast-enhanced (DSC)-MRI and
      diffusion-weighted MRI. MATERIAL AND METHODS: Newborn piglets (n = 12/17) were
      reoxygenated with 21% (n = 6) or 100% O2 (n = 6) after global hypoxia. Five
      piglets served as controls. CEUS and MRI were performed before, during, and up to
      7 hours after hypoxia. Following are the perfusion parameters for CEUS: peak
      intensity (PI), area under the curve (AUC), time to peak (TTP), and upslope a and
      perfusion/diffusion parameters for MRI: relative cerebral blood volume, relative
      cerebral blood flow, mean transit time, and apparent diffusion coefficient were
      compared between different regions in the brain across time points and also
      compared with histology at the end. RESULTS: In CEUS, compared with the control
      group, perfusion changed significantly over time, in the hyperoxic group in all
      regions for PI, AUC in all regions of interests. The changes presented mainly as
      decreased perfusion during and shortly after resuscitation: for PI in the basal
      ganglia (BG), cortex, and the whole brain with 50 to 60% (P <= 0.001); for AUC in
      the BG and cortex with 90% (P <= 0.02) and in the whole brain with 70% (P =
      0.004). In the injured brains (confirmed by histology), significant changes over
      time were seen in TTP and AUC with mainly increased perfusion during hypoxia: for
      TTP in the cortex, AUC in the BG and whole brain with 90 to 100% (P <= 0.04), and
      for TTP in the whole brain with 50% (P = 0.02). DSC-MRI showed the same trends in
      perfusion with regard to relative cerebral blood volume as CEUS. In all pigs
      exposed to hypoxia, perfusion returned toward baseline values at 7 hours after
      hypoxia in both methods. Apparent diffusion coefficient decreased significantly
      after 7 hours in the injured brains in the BG from 114.6 +/- 1.2 * 10mm/s to 90.3
      +/- 24 * 10 mm/s (P = 0.03). CONCLUSIONS: CEUS and DSC-MRI can detect an early
      temporal evolution of cerebral perfusion in perinatal hypoxia and resuscitation,
      reversible after 7 hours. Hyperoxic resuscitation caused early decreased cerebral
      perfusion, not present in the normoxic group. The combined use of CEUS and DSC
      MRI can provide important diagnostic information and give new insights into
      perinatal vascular hypoxia mechanisms.

PMID- 21730874
TI  - CT perfusion of renal cell carcinoma: impact of volume coverage on quantitative
      analysis.
AB  - PURPOSE: To assess the feasibility, image quality, and radiation dose of computed
      tomography (CT) renal perfusion imaging in the adaptive 4-dimensional (4D)-spiral
      mode in patients with renal cell carcinoma (RCC), and to compare quantitative
      measurements between 2-dimensional regions-of-interest (2D-ROI) and 3-dimensional
      volumes-of-interest (3D-VOI). MATERIALS AND METHODS: Twenty-one patients (13
      male; age, 67.4 +/- 9.5 years) with 24 histologically proven RCCs underwent CT
      perfusion imaging (100 kV, 100 mAs/rotation, scan range 10 cm, examination time
      40.17 seconds) in a 4D-spiral mode with dual-source 128-slice CT. The ability to
      suspend respiration during CT perfusion imaging was visually monitored. Two
      independent readers assessed motion artifacts of CT perfusion imaging data sets
      on a 4-point scale before and after automated motion correction. Qualitative
      (enhancement pattern) and quantitative perfusion analysis (blood flow [BF], blood
      volume [BV], flow extraction product [KTrans]) were performed in the tumor and in
      healthy ipsi- and contralateral renal cortex applying the maximum-slope and a
      modified Patlak approach for quantitative analysis in 2D-ROI and 3D-VOI, the
      latter including the entire RCCs. RESULTS: Of the 21 patients, 8 (38%) could
      suspend respiration throughout the perfusion scan. Of 21 RCCs, 18 (86%) were
      completely included in the scan range. Motion artifacts were significantly
      reduced after automated motion correction (P < 0.001). All 24 RCCs could be
      included in the qualitative perfusion analysis, and 22 of 24 (92%) were eligible
      for quantitative perfusion analysis. Enhancement was homogenous in 4 (17%),
      peripheral in 4 (17%), and heterogeneous in 16 (66%) tumors (good interobserver
      agreement, kappa=0.74). A high correlation was found between the 2 readers
      regarding quantitative perfusion parameters (r=0.93-0.94, P < 0.01). Quantitative
      measurements in 3D-VOIs revealed significantly lower BV, BF, and K in RCCs than
      in normal renal cortex (P < 0.001). In solid tumor periphery, BV was similar to
      the renal cortex (P=0.299), while BF and K were significantly lower (P < 0.01 and
      <0.001) in tumor tissue. Comparison of tumor measurements in 3D-VOIs with those
      obtained from 2D-ROIs revealed considerable differences in perfusion parameters
      beyond the 95% confidence limits in 46% to 68% of the tumors. KTrans was
      significantly higher in the contralateral than in healthy ipsilateral renal
      cortex (P < 0.01). Estimated effective radiation dose of the CT perfusion
      protocol was 16.3 mSv. CONCLUSION: CT perfusion imaging using an adaptive 4D
      spiral mode is feasible and enables, after use of automated motion correction,
      the reliable analysis of renal perfusion in patients with RCCs. Considerable
      tumor heterogeneity was found, with differences in perfusion parameters between
      2D-ROI and 3D-VOI analysis, reinforcing the use of volumetric techniques for
      perfusion imaging and analysis. Differences between ipsi- and contralateral
      healthy renal cortex KTrans suggest a compensatory increase in glomerular
      filtration rate in the healthy contralateral kidney.

PMID- 21730875
TI  - Dorsal distal radius fractures in children:  role of plaster in redisplacement of
      these fractures.
AB  - The aim of this study was to retrospectively identify the role of plaster in
      redisplacement of dorsal distal radius fracture in children. A total of 60
      children with displaced dorsal distal radius fractures were included in this
      study. All these fractures were reduced under general anesthesia. A total of 22
      redisplacements were observed. Statistical analysis was performed to search for
      risk factors of redisplacement. Poor modeling immobilization of the wrist in the
      cast, studied by the three-point index was the only significant risk factors for
      redisplacement. The three-point index is an excellent index to predict
      redisplacement and assess the quality of the cast treatment of these fractures.
      The type of study or level of evidence is therapeutic IV.

PMID- 21730876
TI  - Risk-adjusted melanoma skin cancer incidence rates in Whites (United States).
AB  - The objective of this study was to obtain a better population-based measure of
      risk for melanoma skin cancer. A method has been previously proposed for
      estimating cancer incidence rates for data collected from the Surveillance,
      Epidemiology, and End Results (SEER) program. Unlike conventionally reported
      incidence rates in the USA, this method uses the first primary cancer and adjusts
      for population-based cancer prevalence to obtain a better measure of cancer risk.
      The study involves SEER data for white men and women. Conventional melanoma
      incidence rates overestimate risk for men, increasingly so from 3.3% in the age
      group of 30-39 years to 11.3% in the age group of 80 years and older.
      Overestimation in risk for women ranged from 3.3% in the age group of 30-39 years
      to 8.9% in the age group of 80 years and older. Overestimation of risk was more
      pronounced when both in-situ and malignant melanomas were considered. Increasing
      trends in conventional rates were slightly greater than trends in risk-adjusted
      incidence rates (RAIRs). In 2007, the estimated number of cases with malignant
      melanoma among the white population based on conventional cancer incidence rates
      is 37 636 (64 125 including in-situ cases) for men and 28 935 (49 361 including
      in-situ cases) for women. The estimated number of cases in the USA based on RAIRS
      is 34 652 [(7.9%); 55 413 (13.6%) including in-situ cases] for male and 27 178
      [(6.1%); 44 467 (9.9%) including in-situ cases] for women. We concluded that
      RAIRs are a better measure of melanoma skin cancer risk and should be used for
      estimating the number of cancer patients in the USA.

PMID- 21730877
TI  - Circulating levels of VEGFR-1 and VEGFR-2 in patients with metastatic melanoma
      treated with chemoimmunotherapy alone or combined with bevacizumab.
AB  - There are no identified biomarkers that could predict response to antiangiogenic
      or traditional chemoimmunotherapy in metastatic melanoma. We hypothesized that
      soluble angiogenic factor receptors might help us to identify patients responsive
      to treatment. A series of 48 patients with stage IV melanoma participating in two
      phase II clinical trials were included. The trials included treatment with
      carboplatin, vinorelbine, and subcutaneous interleukin-2 (n=22) or treatment with
      bevacizumab, dacarbazine, and low-dose interferon-alpha2a (n=26).Serum samples
      were prospectively collected and soluble vascular endothelial growth factor
      receptor 1 (s-VEGFR-1) and 2 (s-VEGFR-2) were measured before starting the trial
      treatment and during response evaluation.There was a trend toward longer overall
      survival among patients with higher-than-median serum VEGFR-1 levels (21.3
      months) compared with 12.3 months in patients with low pretreatment s-VEGFR-1
      levels (P=0.146). Pretreatment s-VEGFR-2 levels did not correlate to survival.
      Serum VEGFR-2 levels decreased during therapy in 44% of the patients and
      increased in 56% of the patients. VEGFR-2 increased in 78% (14 of 18) of the
      patients who progressed during therapy (P=0.017). VEGFR-2 decrease was associated
      with clinical benefit in 65% of the patients (11 of 17) and with progression in
      only four patients (P=0.016).High pretreatment levels of s-VEGFR-1 are associated
      with improved prognosis among patients with metastatic melanoma independently on
      therapy, whereas increased VEGFR-2 levels during therapy are associated with
      disease progression. These markers might be useful in selecting patients
      responsive to antiangiogenic therapy.

PMID- 21730878
TI  - Lymph node ultrasound during melanoma follow-up significantly improves metastasis
      detection compared with clinical examination alone: a study on 433 patients.
AB  - Early detection of melanoma metastases is essential for effective treatment and
      may be crucial for the prevention of systemic metastases and patient survival.
      However, data demonstrating the reliability and accuracy of ultrasound
      examination for the detection of lymph node metastases, in addition to clinical
      examination, are rare. We have examined 433 melanoma patients with stage
      dependent follow-up intervals of 3 to 12 months. One thousand three hundred and
      thirty-two paired clinical and nonblinded sonographic tests of the locoregional
      lymph node areas were performed. Lesions suspicious of melanoma metastases were
      examined histopathologically. Of note, sensitivity [0.9394 (95% confidence
      interval: 0.7977-0.9926)] and specificity [0.9808 (95% confidence interval:
      0.9717-0.9875)] of combined clinical and sonographic investigations were
      significantly (P<0.0001) higher than clinical results alone. Significant
      differences between clinical follow-up and sonographically assisted follow-up
      were found for American Joint Committee on Cancer 2002 melanoma stages I
      (P=0.0389), III (P=0.0101), and IV (P=0.0016). For stage II melanoma, a trend was
      detected (P=0.0821). Lymph node metastases were detected sonographically in 1.73%
      of clinically metastasis-free investigations (n=22). Our data suggest that high
      frequency sonography should be part of all melanoma follow-up investigations,
      independent of melanoma type, melanoma stage, or lymph node biopsy status.

PMID- 21730879
TI  - Treatment options for dysfunctional uterine bleeding.
AB  - The diagnosis and treatment of dysfunctional uterine bleeding can be a long
      emotional journey for the patient and a difficult challenge for the provider.
      This article provides NPs with a practical overview of the process from chief
      complaint to follow-up care.

PMID- 21730880
TI  - Let the evidence determine vitamin D deficiency.

PMID- 21730881
TI  - Ossiculoplasty with total ossicular replacement prosthesis and Omega Connector:
      early clinical results and functional measurements.
AB  - OBJECTIVE: Among other difficulties, achieving a stable position of a total
      ossicular replacement prosthesis (TORP) is demanding because of a limited view on
      the TORP-footplate interface and individual angles between the footplate and
      tympanic membrane. The Kurz Omega Connector aims at a simplified insertion of the
      TORP. The performance of total ossicular reconstruction using the Omega Connector
      was evaluated. STUDY DESIGN: Prospective cohort study and experimental
      measurements with a fresh human temporal bone. SETTING: Tertiary referral center.
      PATIENTS: Seventeen consecutive patients receiving total ossicular reconstruction
      were included. Historical control group composed of 36 patients. INTERVENTIONS:
      Total ossicular reconstruction using the Omega Connector. MAIN OUTCOME MEASURES:
      (a) Handling of the TORP and Omega Connector intraoperatively, (b) functional
      short-term results compared with a historical control group, (c) sound
      transmission properties with 3 different connective positions between the TORP
      and the Omega Connector. RESULTS: Placing the Omega Connector on the footplate
      and coupling the Omega Connector to the TORP was straightforward in 65% of cases.
      A stable final position of the TORP was obtained in 88% of cases. Mean (SD)
      preoperative and postoperative air-bone gaps were 36.00 (11.05) and 25.29 (12.25)
      dB and were almost identical with those in the historical control group (p =
      0.9). In the experimental measurements, functional outcomes with "partial
      connection" showed almost the same results as those with "full connection."
      CONCLUSION: The Omega Connector provides easy handling of the TORP. The short
      term functional results were comparable to those achieved previously without the
      Omega Connector. The temporal bone measurement supports tolerance in connective
      position between the TORP and the Omega Connector.

PMID- 21730882
TI  - Hearing preservation after complete cochlear coverage in cochlear implantation
      with the free-fitting FLEXSOFT electrode carrier.
AB  - OBJECTIVES: To demonstrate the possibility of atraumatic insertion with the free
      fitting FLEX electrode by evaluating the degree of hearing preservation
      postoperatively. DESIGN: Retrospective study. SETTING: Academic tertiary care
      center. PARTICIPANTS: Twenty-two severely to profoundly hearing impaired subjects
      with measurable residual hearing preoperatively. INTERVENTION: Atraumatic
      implantation with the 31.5-mm-long, free-fitting, and highly flexible FLEX
      electrode using either the round window approach or a cochleostomy technique.
      MAIN OUTCOME MEASURES: Subjects were tested preoperatively in unaided condition
      and at varying intervals postoperatively. Preoperative and postoperative low
      frequency pure-tone average (PTA) and PTA shifts were calculated. Speech
      perception was measured preoperatively and postoperatively using the Freiburger
      monosyllabic word test in quiet. RESULTS: Preoperative low-frequency hearing
      could be preserved to a certain degree in 77.3% of subjects (17/22) after
      insertion of the FLEX electrode up to the point of first resistance. Complete
      loss of residual hearing was observed in 22.7% of subjects (5/22). In 18.2% of
      the subjects (4/22), the preoperative PTA was preserved within 10 dB. Pure-tone
      average results between preoperative and most recent testing showed statistically
      significant differences (p < 0.001 to p = 0.031) for almost all loudness levels
      ranging from 125 Hz to 1.5 kHz. The maximum threshold shift was 40 dB at 250 Hz
      for the lower frequencies up to 1 kHz. Monosyllable testing in quiet demonstrated
      significant improvement over time (p < 0.001). CONCLUSION: This study showed that
      preservation of residual hearing is possible in a high number of subjects when a
      flexible electrode and atraumatic surgical techniques are used.

PMID- 21730883
TI  - Superficial siderosis of the central nervous system: phenotype and implications
      for audiology and otology.
AB  - OBJECTIVE: Superficial siderosis of the central nervous system (SSCN) results
      after chronic subarachnoid hemorrhage. Consequent demyelination, particularly of
      the cochleovestibular nerve and cerebellum, causes auditory-vestibular
      dysfunction. Predominant symptoms include progressive sensorineural hearing loss,
      imbalance, and ataxia. Despite characteristic auditory-vestibular involvement,
      SSCN is not well known among the hearing health community. STUDY DESIGN: Clinical
      records of 49 patients diagnosed with SSCN were reviewed. Analysis included
      review of demographic, audiometric, and vestibular data of the largest sample to
      date and comparison to 31 audiovestibular case reports in the literature.
      RESULTS: Hearing loss and disordered balance were reported by 92% and 67% of
      patients, respectively. Results suggest variable but substantial auditory
      vestibular involvement related to SSCN. Hearing loss is typically progressive,
      sloping, and asymmetric and exceeds hearing loss expected based on age or sex.
      Decreased word recognition is possible and traditional amplification may fail to
      provide benefit. CONCLUSION: SSCN is a destructive disorder affecting the
      auditory-vestibular system. Although not a common diagnosis, SSCN may be more
      prevalent than clinicians realize. Site of lesion may be anywhere within the
      auditory-vestibular system from the inner ear to the cortex, although the
      cochleovestibular nerve and cerebellum are particularly vulnerable. The
      progressive retrocochlear nature of the disorder makes differential diagnosis
      difficult and development of effective treatment options challenging. It is
      essential that audiologists and otologists recognize this uncommon cause of
      sensorineural hearing loss and balance disorder and the implications for
      evaluation, treatment, and counseling.

PMID- 21730884
TI  - Cisplatin ototoxicity affecting cochlear implant benefit.
AB  - OBJECTIVE: Report a case of loss of cochlear implant benefit after cisplatin
      therapy to treat osteosarcoma. Examine the implications for the loci of cisplatin
      associated cochleotoxicity. STUDY DESIGN: Retrospective case review. SETTING:
      Tertiary referral center. PATIENTS: Single case study. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Cochlear implant programming levels. RESULTS: Increase
      in cochlear implant programming T- and C-levels after cisplatin therapy.
      CONCLUSION: Cisplatin therapy likely affects spiral ganglion cells. It seems that
      auditory cells other than outer hair cells in the organ of Corti are affected by
      cisplatin because the hearing sensitivity of this patient with nonfunctioning
      outer hair cells declined after receiving chemotherapy. Implications of these
      findings are discussed.

PMID- 21730885
TI  - Central venous catheter-related blood stream infections in children undergoing
      hematopoietic stem cell transplant for primary immunodeficiency and other
      nonmalignant disorders.
AB  - A single-center experience of catheter-related blood stream infections in
      children undergoing hematopoietic stem cell transplant for primary
      immunodeficiency is described. The rate of definite central venous catheter
      infections was 5.31/1000 line days. Staphylococcus epidermidis was the most
      commonly identified organism. Teicoplanin resistance occurred in 17% of S.
      epidermidis infections. The central catheter was removed in 21% of infections.

PMID- 21730886
TI  - Treatment of Kaposi sarcoma in human immunodeficiency virus-1-infected Mozambican
      children with antiretroviral drugs and chemotherapy.
AB  - AIDS-associated Kaposi sarcoma occurs in children, but treatment experience
      reports are very scarce. A retrospective analysis of 28 children treated with
      highly active antiretroviral therapy and monthly paclitaxel showed unexpected
      results with 19 children in complete and sustainable remission, including those
      with the most severe form. Tolerance and feasibility were good, despite a lack of
      skilled staff in a low-resource setting.

PMID- 21730887
TI  - Hyperinflammatory pulmonary disease in chronic granulomatous disease.

PMID- 21730888
TI  - Hemorrhagic shock and encephalopathy syndrome in a child with pandemic H1N1 2009
      influenza virus.
AB  - We report a case of hemorrhagic shock and encephalopathy in a child with pandemic
      2009 H1N1 influenza infection. The patient succumbed within 3 days of admission.

PMID- 21730890
TI  - Relevance of measuring circulating microparticles during organ and stem-cell
      transplantation.

PMID- 21730889
TI  - Apolipoprotein A1 and C-terminal fragment of alpha-1 antichymotrypsin are
      candidate plasma biomarkers associated with acute renal allograft rejection.
AB  - BACKGROUND: Current diagnostic methods of renal allograft rejection are neither
      sensitive nor specific. Needle biopsies are invasive and associated with patient
      morbidity. Thus, it is desirable to develop noninvasive tests to predict and
      diagnose rejection. METHODS: Using a case-control approach, surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry was used to identify
      plasma proteins associated with renal allograft rejection. From each rejection
      patient (n=16), two plasma samples (one near the biopsy date and the other at a
      time postbiopsy) were compared. Biopsy-confirmed nonrejection patients (n=48)
      were further analyzed as controls. Antibody-based quantitative enzyme-linked
      immunosorbent assay was performed to validate candidate biomarker apolipoprotein
      A1 (Apo A1) in a subset of the original and a second cohort of biopsy-confirmed
      rejection (n=40) and nonrejection (n=70) patients. RESULTS: Twenty-two
      proteins/peptides showed significant differences between rejection and
      postrejection samples. Peptides 5191 Da and 4467 Da detected rejection with 100%
      sensitivity and 94% specificity. The 4467 Da peptide was identified as the C
      terminal fragment of alpha-1 antichymotrypsin and a 28 kDa protein was determined
      as Apo A1. Both protein levels were significantly lower at rejection compared
      with postrejection. Protein levels of nonrejection patients were similar to the
      postrejection samples. Apo A1 enzyme-linked immunosorbent assay results showed
      significantly lower Apo A1 levels (P=0.001 for the original and P=4.14E-11 for
      the second cohort) at the time of rejection compared with nonrejection which
      coincides with the SELDI findings. CONCLUSIONS: Together alpha-1
      antichymotrypsin, Apo A1, and the unidentified 5191 Da peptide provide a plasma
      molecular profile, and this is associated with acute cellular renal allograft
      rejection.

PMID- 21730891
TI  - What do we need to change in NICU nursing practice?

PMID- 21730894
TI  - The analgesic properties of intraoral sucrose: an integrative review.
AB  - The treatment of pain is an essential component of the clinical and ethical care
      of infants. Despite evidence-based practice consensus statements recommending
      that infants receive analgesia during minor painful procedures, numerous studies
      have shown that procedural pain remains poorly managed in this population. Oral
      sucrose administration has been associated with calming effects and reductions in
      observed pain behaviors with preterm and term infants aged up to 1 year. The
      objective of this integrative review is to synthesize findings from published
      randomized controlled trials evaluating the efficacy and safety of oral sucrose
      as a preprocedural intervention for mild to moderate procedural pain in infants.
      Overall, studies indicate that oral sucrose is an effective, safe, convenient,
      and immediate-acting analgesic for reducing crying time and significantly
      decreases biobehavioral pain response following painful procedures with infants.

PMID- 21730896
TI  - Simulation training: a multidisciplinary approach.
AB  - Emergency situations arise in health care every day. High-risk environments such
      as Neonatal Intensive Care Units and labor and delivery units are more
      susceptible to such emergencies. Occasionally, newborns require assistance with
      their breathing in the delivery room, while others demand intensive resuscitation
      including intubation and chest compressions. Delivering resuscitative efforts can
      be difficult when the team trains in separate venues. This article will discuss
      the importance of multidisciplinary high-fidelity simulation training as an
      effective tool in the development and maintenance of resuscitation expertise
      across disciplines, the history of simulation, simulation legislation, and the
      evidence behind simulation and explore the art and utilization of medical
      simulation in a multidisciplinary setting.

PMID- 21730897
TI  - Familial hemophagocytic lymphohistiocytosis in the neonate.
AB  - Familial hemophagocytic lymphohistiocytosis is a rare and inherited disease that
      affects both males and females equally and is most often fatal if not treated.
      Diagnosis is challenging because it mimics severe sepsis by demonstrating
      hepatomegaly, splenomegaly, persistent fever, central nervous system involvement,
      and cytopenias. The etiologies of hemophagocytic lymphohistiocytosis have been
      well established through the identification of 3 causative genetic mutations.
      Therapies for hemophagocytic lymphohistiocytosis focus on restoring health by
      diminishing the disease sequelae with a goal of hematopoietic stem cell
      transplant, the only known curative therapy for hemophagocytic
      lymphohistiocytosis. Current research is being conducted to identify other
      causative genetic mutations and newer, more effective treatment modalities.

PMID- 21730898
TI  - A model of collaboration and efficiency between neonatal nurse practitioner and
      neonatologist: application of collaboration theory.
AB  - A model of clinical practice involving neonatal nurse practitioners (NNP) and
      neonatologists is presented through the application of collaboration theory. This
      strategy has been used in business and other applications. In this article, the
      terms and principles of the model will be explained. The relevant features will
      be identified, including interdependence, communication, strategic negotiation,
      independent billing, NNP licensure support, semiformal systems, and radical
      tailorability. Recommendations for structure and components to ensure safe
      practice involving the unique contributions of the NNP will be highlighted. An
      example of such a successful practice will be described.

PMID- 21730899
TI  - Implementing an MSN nursing program at a distance through an urban-rural
      partnership.
AB  - Recruiting, retaining, and educating advanced practice nurses is essential to
      meet the growing need for advanced practice nurses in rural and urban
      communities. Through the support of Health Resources and Services Administration
      funding, the urban school of nursing expanded its MSN program and implemented the
      graduate curriculum on its rural campus by utilizing emerging online and distance
      education technologies. The purpose of this manuscript is to provide an overview
      of expanding an existing MSN program offered in an urban, traditional classroom
      setting to rural graduate nursing students via an online synchronous format. In
      addition, the article will describe the rural growth of the existing neonatal
      nurse practitioner program as an exemplar and the different methodologies that
      are being used in each program to engage the rural nurse practitioner students in
      clinical courses. In addition, strategies to address barriers related to rural
      nurse practitioner student recruitment and retention will be discussed.

PMID- 21730900
TI  - Integration of kangaroo care into routine caregiving in the NICU: what is
      stopping you?

PMID- 21730901
TI  - Effect of a dedicated percutaneously inserted central catheter team on neonatal
      catheter-related bloodstream infection.
AB  - PURPOSE: To evaluate whether the establishment of a dedicated percutaneously
      inserted central catheter (PICC) team is associated with reduced risk of catheter
      related bloodstream infection (CRBSI) in the neonatal intensive care unit.
      SUBJECTS: Participants were extremely low-birth-weight infants admitted to a
      level IIIC neonatal intensive care unit. DESIGN: A before- versus after
      intervention study design was implemented. Intervention group participants were
      admitted after April 2006 when the PICC team was established, dedicating line
      insertion and maintenance responsibilities to the team. Historical control group
      participants were managed via the previous standard of care. METHODS: The risk of
      CRBSI over time was estimated by Kaplan-Meier analyses and the effect of the PICC
      team on CRBSI risk was evaluated after controlling for covariables in a Cox
      proportional hazards model. PRINCIPAL RESULTS: Mean birth weight and gestational
      age were similar between groups. After controlling for gestational age, central
      line days, respiratory support days, and average daily census at time of
      admission in a Cox regression model, the intervention group had 49% lower risk of
      CRBSI in patients who had a central line in place for more than 30 days. There
      was no difference in rate of CRBSI between groups that had central lines of short
      or intermediate duration (<30 days). CONCLUSIONS: Catheter-related bloodstream
      infection in extremely low-birth-weight infants requiring long-term central
      venous access was reduced by nearly half after the institution of a dedicated
      PICC team in the neonatal intensive care unit. Standardizing PICC line placement
      is important, but standardizing line maintenance is essential to improvement of
      CRBSI rates.

PMID- 21730902
TI  - Effect of the premature infant oral motor intervention on feeding progression and
      length of stay in preterm infants.
AB  - PURPOSE: Preterm infants frequently experience oral feeding difficulties due to
      underdeveloped oral motor skills and the lack of coordination of sucking,
      swallowing, and respiration. The infants' ability to consume all feedings orally
      while maintaining physiologic stability and weight gain is necessary for their
      discharge. Therefore, difficulty with oral feeding leads to longer hospital stays
      and higher costs. For example, with more than half a million of premature infants
      born each year, a 3-day decrease in hospital stay would save more than 2 billion
      dollars annually. There is a need for evidenced-based interventions that
      facilitate development of oral-motor skills, leading to improved oral feeding,
      thus shortening hospital stays and lowering costs. The purpose of this research
      was to test the newly developed Premature Infant Oral Motor Intervention (PIOMI)
      beginning at 29 weeks postmenstrual age (PMA), before oral feedings were
      introduced, to determine whether the prefeeding intervention would result in a
      shorter transition from gavage to total oral feedings and a shorter length of
      hospital stay (LOS). The PIOMI is a 5-minute oral motor intervention that
      provides assisted movement to activate muscle contraction and provides movement
      against resistance to build strength. The focus of the intervention is to
      increase functional response to pressure and movement and control of movements
      for the lips, cheeks, jaw, and tongue. The cheeks (internal and external), lips,
      gums, tongue, and palate were stimulated per specific protocol with finger
      stroking. SUBJECTS: A total of 19 infants from 1 level III NICU born between 26
      and 29 weeks PMA: 10 in the experimental group and 9 in the control group.
      DESIGN: A randomized, blinded, clinical trial was conducted to examine outcomes
      related to the newly developed PIOMI. METHODS: Beginning at 29 weeks PMA (and
      before the introduction of oral feeding), the experimental group received the
      PIOMI for 5 minutes per day for 7 consecutive days. The control group received a
      sham intervention to keep staff and parents blinded to the infants' group
      assignment. Physiological and behavioral stabilities were continually assessed
      throughout the intervention. A chart review was then conducted to compare the
      transition from gavage feeding to total oral feedings between the experimental
      and control group, as well as LOS. RESULTS: The PIOMI was well tolerated by 29
      week PMA infants, as evidenced by physiological and behavioral cues. Infants who
      received the once-daily PIOMI transitioned from their first oral feeding to total
      oral feedings 5 days sooner than controls (P = .043) and were discharged 2.6 days
      sooner than controls. CONCLUSION: This pilot work supports further study on the
      use of the PIOMI with preterm infants to enhance oral-feeding skills and decrease
      LOS.

PMID- 21730903
TI  - Professional boundaries in an electronic age.

PMID- 21730904
TI  - Member spotlight, 2011 conference, neonatal procedural skills lab, new online
      member community, and product spotlight.

PMID- 21730906
TI  - Feeding intolerance: a concept analysis.
AB  - Feeding intolerance is a well-known phenomenon in the NICU and is linked to
      morbidity and mortality in the premature infant. However, a universal definition
      for this concept is lacking. Properly defining a concept is a key step in a
      successful research project. A concept analysis is an examination of the
      fundamental elements of a concept to bring clarification and definition to the
      topic of interest. The purpose of this concept analysis was to clarify the
      phenomenon of feeding intolerance in the premature infant and to provide a
      universal conceptual and operational definition for researchers and clinicians to
      use in practice theory.

PMID- 21730907
TI  - Necrotizing enterocolitis in the premature infant: neonatal nursing assessment,
      disease pathogenesis, and clinical presentation.
AB  - Necrotizing enterocolitis (NEC) remains one of the most catastrophic
      comorbidities associated with prematurity. In spite of extensive research, the
      disease remains unsolved. The aims of this article are to present the current
      state of the science on the pathogenesis of NEC, summarize the clinical
      presentation and severity staging of the disease, and highlight the nursing
      assessments required for early identification of NEC and ongoing care for infants
      diagnosed with this gastrointestinal disease. The distributions of systemic and
      intestinal clinical signs that are most sensitive to nursing assessment and
      associated with Bell Staging Criteria are presented. These descriptive data are
      representative of 117 cases of NEC diagnosed in low-gestational-age infants (<29
      weeks' gestation). The data highlight the clinical signs most commonly observed
      in infants with NEC and thus provide NICU nurses an evidence-based guide for
      assessment and care of infants with NEC.

PMID- 21730909
TI  - Congenital central hypoventilation syndrome: a case report.
AB  - Congenital central hypoventilation syndrome (CCHS) is a relatively rare, life
      threatening, and lifelong multisystem disorder characterized by autonomic nervous
      system dysfunction, which mostly manifests as failure to maintain ventilatory
      homeostasis during sleep. Infants with CCHS have inadequate sensitivity to
      hypoxia and hypercapnia during sleep and in some cases during wakefulness,
      leading to persistent apnea. This article reports a case of CCHS in a 38-week
      gestation infant who presented on day of life 2 with persistent apnea. Diagnosis
      of primary pulmonary, cardiac, metabolic, neurologic disease, or injury was
      excluded before the diagnosis of CCHS was made. The diagnosis was confirmed by a
      PHOX2B sequence analysis. A tracheotomy was performed and the infant was
      discharged home on a home ventilator with outpatient follow-up. The clinical
      presentation of CCHS, as well as diagnosis and treatment strategies, is reviewed.

PMID- 21730910
TI  - Update on immunizations commonly used in the NICU.
AB  - With few exceptions, it is currently recommended that all premature infants
      should receive routine childhood vaccines at the same chronologic age as term
      infants. Thus, neonatal nurses need to stay current on the recommendations for
      immunizations commonly used in the NICU setting. It is important for nurses to
      provide information that is reliable and verifiable with scientific evidence to
      the parents.

PMID- 21730911
TI  - Immunizations.

PMID- 21730912
TI  - Systematic review of the literature: parental outcomes after diagnosis of fetal
      anomaly.
AB  - Advancing technology has made detecting fetal abnormalities in the first and
      second trimesters a reality. Few families are prepared for the difficult
      decisions that must be made if their unborn children are diagnosed with a life
      limiting condition. Expectant parents are compelled to make decisions on the
      basis of limited options. A systematic review of the literature is presented with
      an aim to inform clinicians of parental experiences and outcomes after diagnosis
      of a fetal anomaly. The review focused on patients given a diagnosis for fetal
      anomalies for the 40-year period from 1970 to 2010 by using the key words such as
      fetal anomaly, congenital malformations, pregnancy termination, perinatal
      palliative care, and perinatal hospice. Regardless of the option taken, women
      often experienced intense grief reactions. Both giving birth to a child with a
      life-limiting condition and termination of pregnancy for fetal anomaly can be
      emotionally traumatic life events, both associated with psychological morbidity.
      Nonaggressive obstetric management, allowing natural birth without life
      sustaining therapeutics, is an option for families. Couples presented with a
      coordinated perinatal palliative care model may opt to continue their pregnancy.
      Families who experienced perinatal hospice/palliative care report positive
      feedback, but more research is needed to explore the psychological outcomes of
      this choice.

PMID- 21730913
TI  - Are we really doing what is best for our tiny patients? NNP shift length and
      patient safety: our time has come.
AB  - In the United States, 20% to 30% of the employed population does shift work.
      Neonatal nurse practitioners are a part of this group. Yet, there are no
      guidelines in place regarding shift length. Fatigue among shift workers is well
      documented and carries risks to both patients and health care providers. It is
      crucial to analyze this problem so that the neonatal nurse practitioner
      profession can move forward with establishing guidelines for practice; so safe,
      quality care to patients is assured and the health as well as the role
      satisfaction of the neonatal nurse practitioner is optimized.

PMID- 21730914
TI  - Incubator humidity: more than just something to sweat about!!

PMID- 21730915
TI  - Heparinized saline vs normal saline for maintenance of intravenous access in
      neonates: an evidence-based practice change.
AB  - PURPOSE: To design, implement, and to evaluate the outcomes of an evidence-based
      practice change regarding the use of heparin in intravenous (IV) locks to improve
      patient safety. Phase I of the project examined dwell time, hours of patency,
      gestational age at birth and at time of IV lock insertion, birthweight and weight
      at time of insertion, and reason for discontinuation for IV access devices prior
      to and following the practice change from heparinized saline (HS) to normal
      saline (NS) flush. Phase II of the project was to determine the effect of the
      educational program on staff knowledge of the use of heparinized saline vs normal
      saline flushes. SUBJECTS: The setting was an 18 bed level III NICU located in the
      northeastern United States. A sample of 70 infants with IV locks were included in
      the study; HS (n = 34) and NS (n = 36) respectively. Infants with IV's that were
      converted to IV locks were excluded. Only professional NICU staff (n = 40) were
      recruited for the educational offering. DESIGN: A comparative descriptive design
      with two components was utilized. METHODS: A retrospective and prospective chart
      review was used to compare the outcomes of neonates with IV locks flushed with
      heparin and normal saline flush and evaluated the outcomes. A pretest/posttest
      design was used to analyze the change of the NICU staff's knowledge concerning
      heparin flush before and after an educational offering. MAIN OUTCOME MEASURES: IV
      lock patency after practice change to NS flush and the change of the NICU staff's
      knowledge concerning heparin flush after an educational offering. PRINCIPAL
      RESULTS: There was a statistically significant difference in IV catheter patency
      with NS flushed catheters averaging 13 hours longer than HS flushed catheters (p
      = 0.02). Also a statistically significant increase in mean scores was noted for
      the NICU staff posttest after the educational offering (p = .0001). There was a
      20% increase in knowledge scores. CONCLUSIONS: Findings from this project support
      the current literature base suggesting that the use of heparin is unnecessary for
      the maintenance of IV access devices. Unnecessary exposure of neonates to heparin
      increases risk to patient safety and should therefore be avoided. Future research
      should examine the use of heparin in central lines in neonates. Findings
      additionally support educating staff prior to practice changes.

PMID- 21730916
TI  - Transition from curative efforts to purely palliative care for neonates: does
      physiology matter?
AB  - OBJECTIVE: To isolate the threshold point in which the goal of care for an infant
      with life-limiting conditions transitions from curative efforts to purely
      palliative care. DESIGN: Descriptive Web-based survey of 285 neonatal physicians
      and nurses who had participated in care of dying infants. METHOD: Researcher
      developed tool measured multiple palliative care concepts related to transition
      to purely palliative care, such as identification of infants for whom purely
      palliative care should be offered; physician and nurse satisfaction with and
      barriers to the transition process; physiological factors that indicated that the
      infant was ready for transition to purely palliative care; publication knowledge
      to guide palliative care; and factors influencing decision making. RESULTS: The
      study aim was to identify the physiology involved in coming to the end of life
      and indicating a transition need for palliative care. But although the
      respondents were able to identify physiological factors or lethal conditions
      leading to a transition to purely palliative care, they stated that these factors
      were not how the goals of care were established. Respondents (96%) stated that
      parental agreement was the determinant to palliative care transition, and,
      regardless of neonatal physiological condition, without agreement, curative
      technological efforts continued. Respondents felt that more education on the
      palliative care process for both staff and families was necessary to move
      dignified end-of-life care forward. CONCLUSIONS: Parents must be our partners
      when the burden of care to the infant is greater than the benefit. Suggestions to
      assist both parents and providers are offered. CLINICAL RELEVANCE: Although this
      study is based on end-of-life decision making for newborns, the findings may
      resonate to nurses who care for dying patients of any age group, with any
      diagnosis, cared for in any type of medical-surgical or critical care unit. The
      findings describe the American concept of patient and family autonomy and
      problems that have arisen from the implementation of autonomy in end-of-life
      decision making regarding withholding/withdrawing therapies that provide
      artificial life support.

PMID- 21730919
TI  - Two new triterpene glycosides with monomethyl malonate groups from the rhizome of
      Cimifuga foetida L.
AB  - Two new 9,19-cycloartane triterpene glycosides 1-2, together with four known
      compounds--26-deoxyactein (3), actein (4), 7,8-didehydro-26-deoxyactein (5) and
      cimiaceroside B (6)--were isolated from the rhizome of Cimicifuga foetida. The
      new triterpene glycosides were identified as 23-O-methyl-24-deoxy-2'-O-(3''
      methylmalonyl)-cimiaceroside B (1) and 2'-O-(3''-methylmalonyl)actein (2) based
      on analysis of their spectral data and chemical reactions.

PMID- 21730920
TI  - An effective ostrich oil bleaching technique using peroxide value as an
      indicator.
AB  - Ostrich oil has been used extensively in the cosmetic and pharmaceutical
      industries. However, rancidity causes undesirable chemical changes in flavour,
      colour, odour and nutritional value. Bleaching is an important process in
      refining ostrich oil. Bleaching refers to the removal of certain minor
      constituents (colour pigments, free fatty acid, peroxides, odour and non-fatty
      materials) from crude fats and oils to yield purified glycerides. There is a need
      to optimize the bleaching process of crude ostrich oil prior to its use for
      therapeutic purposes. The objective of our study was to establish an effective
      method to bleach ostrich oil using peroxide value as an indicator of refinement.
      In our study, we showed that natural earth clay was better than bentonite and
      acid-activated clay to bleach ostrich oil. It was also found that 1 hour
      incubation at a 150  degrees C was suitable to lower peroxide value by 90%. In
      addition, the nitrogen trap technique in the bleaching process was as effective
      as the continuous nitrogen flow technique and as such would be the recommended
      technique due to its cost effectiveness.

PMID- 21730921
TI  - Calcitonin gene related peptide: a new ally in cardiac ischemic disease.

PMID- 21730922
TI  - The fluid balance in the critically ill patients: what are we talking about?

PMID- 21730923
TI  - Sevoflurane as a potential replacement for halothane in diagnostic testing for
      malignant hyperthermia susceptibility: results of a preliminary study.
AB  - BACKGROUND: To diagnose malignant hyperthermia (MH) susceptibility, muscle
      bundles are exposed to halothane and caffeine. We investigated whether
      sevoflurane, which is more clinically relevant but less potent of an anesthetic,
      could replace halothane in diagnostic MH testing. METHODS: With prior written
      consent, muscle bundles from 6 malignant hyperthermia susceptible (MHS) and 5 non
      susceptible (MHN) individuals were exposed to increasing concentrations of
      sevoflurane (1.3; 2.6; 5.2 vol%). In addition, muscles from 9 MHS and 8 MHN were
      tested with a rapid exposure to 8 vol% of sevoflurane. Maximal contractures were
      measured and statistically analyzed (Mann-Whitney-U-test; P<0.05). RESULTS: There
      were no differences in weight, length or pre-drug tension of the muscle bundles.
      Incremental sevoflurane concentrations induced no differences in contracture
      between susceptible and non-susceptible muscles. The rapid application of
      sevoflurane induced significant contractures in all malignant hyperthermia
      susceptible compared with non-susceptible individuals. CONCLUSION: The rapid
      application of a high sevoflurane concentration but not an increasing stepwise
      application allowed for the diagnostic discrimination of susceptible individuals.

PMID- 21730924
TI  - Multidetector computed tomography (MDCT) for preoperative airway assessment in
      children with mucopolysaccharidoses.
AB  - BACKGROUND: Accumulation of glycosaminoglycans is known to cause significant
      problems in the anesthetic management of children with mucopolysaccharidoses
      (MPS). Clinical and standard radiological evaluation may convey insufficient
      information about the upper airway and trachea in children with MPS.
      Multidetector computed tomography (MDCT) images have been used to define the
      central airway and previous studies have recommended this tool to assess the
      airway of children who are considered at risk of difficult intubation. However,
      MDCT has not been recommended in MPS children. The aim of this clinical scenario
      study was to verify whether information from MDCT reconstruction of the airway is
      useful in airway management planning of children with MPS. METHODS: In a two
      phase questionnaire-based study, 26 pediatric anesthesiologists were asked to
      produce airway management plans for 5 children with MPS. An initial plan for
      airway control was reported after assessment of standard preoperative anesthetic
      charts. A subsequent airway strategy was then described after reviewing tracheal
      MDCT images of each patient. RESULTS: MDCT images provided additional clinically
      relevant information in 87% (95% CI: 79-92%) of the evaluations. Reduction of
      tracheal size was the most common finding provided by the MDCT images. After
      reviewing the MDCT images, anesthesiologists changed their primary airway device
      selection in 21% of the evaluations (P=0.01). CONCLUSION: Airway reconstruction
      using MDCT images from a previous CT scan may provide a useful assessment tool
      for preoperative airway evaluation and planning in MPS children.

PMID- 21730925
TI  - Intrathecal atropine to prevent postoperative nausea and vomiting after Cesarean
      section: a randomized, controlled trial.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is a common adverse effect
      of intrathecal morphine, especially after Cesarean section. This randomized
      controlled trial investigated the effects of intrathecal administration of a
      small-dose of atropine on postoperative nausea and vomiting after Cesarean
      section. METHODS: Parturients with ASA physical status class I-II scheduled for
      elective Cesarean section and consenting to spinal anesthesia were enrolled. They
      received 0.5% hyperbaric bupivacaine 12.5 mg, morphine 200 ug and one of the
      following three solutions: atropine 100 ug intrathecally and saline
      intravenously; saline intrathecally and atropine 100 ug intravenously; saline
      only both intravenously and intrathecally. We examined the incidence and severity
      of PONV, pain ratings and the need for analgesics. RESULTS: We followed 204
      parturients. The incidence of PONV was 15%, 37% and 49% in the three groups,
      respectively (P<0.001). The relative risk reduction for PONV when using
      intrathecal atropine was 69% vs. placebo and 59% vs. intravenous atropine. No
      differences were noted in terms of postoperative pain. CONCLUSION: Intrathecal
      atropine had a significant antiemetic effect, making it a useful adjunct for
      intrathecal opioid-related PONV.

PMID- 21730926
TI  - Differential effects of the calcitonin gene-related peptide on cardiac
      performance in acute myocardial ischemia and reperfusion in isolated rat hearts.
AB  - BACKGROUND: The cardioprotective effects of the calcitonin gene-related peptide
      (CGRP) are known; however, the profiles of CGRP given pre- and postischemia as a
      therapeutic agent in acute myocardial ischemia and reperfusion remain elusive.
      METHODS: The effects of CGRP on cardiac performance in isolated rat hearts
      subjected to 50 min global ischemia followed by 60 min reperfusion were
      investigated. RESULTS: It was found that global ischemia and reperfusion
      significantly decreased left ventricular developed pressure (LVDP) and heart rate
      (HR) and elevated left ventricular end diastolic pressure (LVEDP). CGRP (10-7
      mol/L) given before the ischemia caused significant increases in LVDP (38+/-9%,
      P<0.05) and HR (16+/-5%, P<0.05), compared to the control. CGRP (administered at
      the beginning of reperfusion) significantly reduced LVEDP and left ventricular
      systolic pressure (LVSP) compared to controls by 30+/-7% and 28+/-7%,
      respectively (P<0.05). When compared to the pre-ischemia treatment, LVEDP and
      LVSP were reduced by 20+/-7% and 26+/-7%, respectively (P<0.05). No significant
      changes in the LVDP and HR were detected when compared to the controls. The
      effects of CGRP could be reversed by CGRP8-37, a specific antagonist of the CGRP
      receptor. CONCLUSION: The results indicated a differential effect of CGRP on
      cardiac performance following acute ischemia/reperfusion.

PMID- 21730927
TI  - Interventional lung assist enables lung protective mechanical ventilation in
      acute respiratory distress syndrome.
AB  - BACKGROUND: The feasibility and safety of a pumpless arteriovenous extracorporeal
      lung assist system (pECLA) has been demonstrated in previous studies of patients
      with severe respiratory insufficiency. The aim of this report was to examine
      whether pECLA is feasible in a center that is new to the technology and to
      determine the positive and adverse effects associated with its use. METHODS: This
      was a retrospective case series of 13 consecutive patients with established acute
      respiratory distress syndrome (ICU patients with ARDS or ALI) at a university
      hospital. Management consisted of transcutaneous placement of a femoral
      arteriovenous pECLA to allow lung-protective ventilation. Nonparametric
      statistics were applied; all data are values and standard deviations (SD).
      RESULTS: Mean simplified acute physiology score (SAPS) II was 49.5 (26); ICU
      mortality was 54% (7/13). Mean length of ICU stay was 34.5 (65.3) days for
      survivors (S) and 36 (32.8) days for non-survivors (NS). Total time on
      arteriovenous pECLA was 12.0 (22.2) days (S) and 7.0(7.8) days (NS), total time
      on mechanical ventilation was 31.0 (28.2) (S) and 32.0 (15.2) days (NS).
      Hypercapnia was significantly (P<0.05) reduced from 80.0 (23.0) (pre-pECLA) to
      48.0 (13.0) mmHg (day 7), as were minute ventilation and inspiratory pressure.
      pECLA was accompanied by a significant (P<0.05) increase in the PaO2/fraction of
      inspired oxygen (P/F) ratio from 100.0 (28.9) (pre-pECLA) to 191.1 (114.3) mmHg
      after 7 days of treatment. Major complications were two inadvertent
      decannulations in the first two patients treated; there was one minor bleeding
      event in a patient seen subsequently. CONCLUSION: pECLA is an effective and
      manageable technique to support gas exchange in ARDS patients. This retrospective
      case series demonstrates the feasibility of pECLA in a center that did not have
      prior experience with this technique. pECLA may decrease further lung injury by
      minimizing the amount of time for which the lung is exposed to high stress and/or
      strain.

PMID- 21730928
TI  - Fluid balance in critically ill patients. Should we really rely on it?
AB  - BACKGROUND: The computation of fluid balances (FBs) by subtracting fluid outputs
      from inputs is a common critical care practice. Limited information exists about
      the accuracy and consistency of nurse-registered cumulative FBs and regarding the
      value of suggested corrections for non-measurable losses. METHODS: From 147 ICU
      patients, we prospectively evaluated the cumulative FBs and their relationship to
      changes in body weight (BW). Standardised measurements of BW were performed on
      admission and discharge. FB charts were accurately reviewed and arithmetic errors
      corrected. Net cumulative FBs and adjusted cumulative FBs (considering sensible
      or insensible fluid losses/fever/liquid faeces) were analysed for all patients
      and 3 subgroups (cardiac-cerebral, septic, and others). Agreement between FBs and
      BW changes was calculated according to the defined subgroups and confounding
      variables. RESULTS: Cumulative FBs were inaccurate in 49 cases (33%) with errors
      ranging from -3606 mL to +2020 mL. The total (average daily) difference between
      measured BW and FBs (mean +/- SD) was 0.185+/-1.874 kg (0.101+/-1.020 kg).
      Correlation (r(2)) and Bland-Altman agreement was poor between BW changes and net
      cumulative FBs (0.552 and -1.26+/-5.41 kg) and slightly better between BW changes
      and adjusted cumulative FBs (0.714 and +0.18+/-3.68 kg). Standard deviations of
      the average daily differences between BW changes and FBs were always >1 L.
      Correction of the net FBs as suggested in the literature were not useful. New
      multiple regression models only modestly improved correlation. CONCLUSION: For a
      large portion of patients nurse-registered cumulative FBs are neither accurate
      nor do they agree with standardised BW measurements. Patient care and clinical
      decision-making should be based on more objective techniques.

PMID- 21730929
TI  - Continuous intravenous infusion of ketamine for maintenance sedation.
AB  - Ketamine HCl is a rapidly acting general anesthetic with sedative and analgesic
      properties that has been reported to have favorable effects on the cardiovascular
      and pulmonary systems. The goal of this review is to determine the hemodynamic
      and pulmonary effects of continuous intravenous (IV) ketamine infusion in
      mechanically ventilated patients, and to determine whether sufficient evidence
      exists to support its use as an agent for maintenance anesthesia. PubMed/Medline,
      EMBASE, and Index Medicus databases as well as relevant bibliographies were
      searched. Studies were independently evaluated for inclusion and exclusion
      criteria, as well as study parameters, by two evaluators. Any discrepancy was
      resolved by a third evaluator. Twenty studies (281 patients) met the inclusion
      criteria for this review including 11 prospective studies (250 patients). Data
      suggests that ketamine decreases airway resistance, improves dynamic compliance,
      and preserves functional residual capacity, minute ventilation and tidal volume,
      while retaining protective pharyngeal and laryngeal reflexes. In patients with
      refractory bronchospasm, continuous infusion of intravenous ketamine decreases
      audible wheeze, bronchodilator requirements, and hypercarbia. It also improves
      respiratory rate and oxygenation, and does not promote respiratory depression.
      Additionally, ketamine does not result in significant perturbations in blood
      pressure, heart rate, or vascular resistance. Ketamine may be a safe and
      effective tool for maintenance sedation of mechanically ventilated patients,
      however a large prospective clinical trial is warranted.

PMID- 21730930
TI  - New approaches for empiric therapy in Gram-positive sepsis.
AB  - Nosocomial bloodstream infections (BSIs) have become an important cause of
      morbidity and mortality, particularly in intensive care units (ICUs). Gram
      positive organisms are the prevalent causes of antibiotic-resistant BSI,
      especially Staphylococcus aureus, coagulase-negative staphylococci and
      enterococci. In recent years, several reports have shown an increase in
      antimicrobial resistance among Gram-positive bacteria isolated from patients in
      ICUs. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is a
      major problem. In the ICU more than 50% of S. aureus isolates in Europe are
      resistant to methicillin. Although vancomycin became the drug of choice for MRSA
      and is still widely used for this indication, many studies suggest that when
      vancomycin MIC values are at the high end of the susceptibility range, vancomycin
      is less effective against MRSA. High MRSA prevalence combined with the widespread
      use of vancomycin for empirical Gram-positive coverage may lead to changes in
      patient outcomes. Here we describe the microbiological, pharmacological and
      clinical characteristics of three new antibacterials helpful in severe infections
      in ICU patients: linezolid, tigecycline and daptomycin. These new drugs have some
      limitations, and the possibility developing resistance is real. Knowledge of both
      old and new antibacterials is necessary to utilize them most effectively.

PMID- 21730932
TI  - The preventive role of higher PEEP in treating severely hypoxemic ARDS.
AB  - This review summarizes knowledge and evidence on the use of positive end
      expiratory pressure (PEEP) in patients with severely hypoxemic acute respiratory
      distress syndrome (ARDS). More specifically, it documents the current evidence on
      the effects of higher PEEP in preventing (or attenuating) lung damage during the
      ventilatory management of patients with severely hypoxemic ARDS. No established
      threshold has been set to define severely hypoxemic ARDS and higher PEEP. In this
      review, those variables are defined as PaO(2)/F(I)O(2) <=100 mm Hg and >=15 cm
      H(2)O, respectively. In ARDS, the intensity of hypoxemia correlated with the
      amount of lung recruitability. In ARDS, the primary objective of PEEP is to
      increase the amount of non-aerated lung at the end of expiration. In early ARDS
      with a diffuse pattern and severe hypoxemia, higher PEEP contributes to lung
      recruitment by maintaining lung recruitment elicited by tidal breath and
      recruitment maneuvers as well as minimizes the repeated opening and closure with
      no significant overdistension. Three clinical trials comparing high PEEP + low
      tidal volume to low PEEP + large tidal volume found benefits favoring the former
      combination. Three large multicenter randomized controlled trials did not
      demonstrate a significant effect on patient outcome of higher or lower PEEP at a
      fixed low tidal volume. The meta-analysis on individual data of these three
      studies showed that the hospital mortality was not significantly different
      between the two groups of patients, was significantly lower in the higher PEEP
      group in the subset of ARDS patients (PaO(2)/F(I)O(2) <=200 mm Hg), and tended to
      be higher in the higher PEEP group in the subset of patients with acute lung
      injury (200< PaO(2)/F(I)O(2) <=300 mm Hg). Therefore, higher PEEP should be used
      in patients with the highest lung recruitability and in the most hypoxemic
      patients. Higher PEEP should be used with caution in patients less severe
      hypoxemic (acute lung injury).To deliver optimal PEEP to those ARDS patients with
      the highest lung recruitability, this technique should be monitored at the
      bedside. Alternative methods are under investigation as part of a decremental
      PEEP trial.

PMID- 21730931
TI  - Sedation in neurocritical patients: is it useful?
AB  - Anesthetics are widely used in the management of neurocritical patients, although
      has never been proved that the use of these drugs can contribute to positive
      outcome. The aim of this review was to evaluate the expected benefit of
      anesthetics use in relation to the altered physiology of the damaged brain while
      considering possible related complications.

PMID- 21730933
TI  - Modification of endotracheal intubation using AirwayScopeTM videolaryngoscope for
      straight reinforced tubes.

PMID- 21730934
TI  - The use of I-gel extraglottic airway during percutaneous dilatational
      tracheostomy: a case series.

PMID- 21730935
TI  - Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.
AB  - Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant
      antibiotic concentrations rather than high peak concentrations are most likely to
      result in effective treatment of infections caused by susceptible bacteria.
      Continuous administration has been suggested as an alternative strategy, to
      conventional intermittent dosing, to optimise beta-lactam
      pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of
      emerging data, we elected to systematically investigate the published literature
      describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics
      administered by continuous or intermittent infusion. We found that the studies
      have been performed in various patient populations including critically ill,
      cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively
      support the administration of beta-lactams via continuous infusion for maximizing
      bacterial killing from consistent attainment of pharmacodynamic end-points. In
      addition, clinical outcome data supports equivalence, even with the use of a
      lower dose by continuous infusion. However, the present clinical data is limited
      with small sample sizes common with insufficient power to detect advantages in
      favour of either dosing strategy. With abundant positive pre-clinical data as
      well as document in vivo PK/PD advantages, large multi-centre trials are needed
      to describe whether continuous administration of beta-lactams is truly more
      effective than intermittent dosing.

PMID- 21730936
TI  - High-dose vitamin D interventional trials: is there reason to pause?

PMID- 21730938
TI  - Rationale and results of percutaneous coronary revascularization with endothelial
      progenitor cell capture stent in high-risk patients requiring undeferrable non
      cardiac surgery.
AB  - AIM: Drug eluting stents (DES) are currently the gold standard for the treatment
      of significant coronary artery stenosis in high risk patients. In case of
      undeferrable non-cardiac surgery their use is still a challenge, due to the need
      of a prolonged dual antiplatelet therapy. We aimed to prospectively evaluate the
      efficacy and safety of the implantation of endothelial progenitor cells (EPC)
      capture stent followed by a short dual anti-platelet therapy (DAT) period in a
      high risk population of patients undergoing undeferrable non-cardiac surgery.
      METHODS: We examined all consecutive patients who received EPCs capture stents
      and underwent non-cardiac surgery within 60 days of percutaneous coronary
      intervention. Our primary outcome was the occurrences of cardiac death,
      myocardial infarction (MI), stent thrombosis (ST), target vessel
      revascularization (TVR) and major adverse cardiac events (MACE). RESULTS: Twenty
      six patients underwent PCI and were enrolled, but only 20 underwent surgical
      intervention. Technical and procedural success rates were both 100%. No
      perioperative MACE was detected. After a mean long term follow-up of 15.4+/-10.3
      months, 2 cases of cardiac death (10%), were recorded. No case of stent
      thrombosis was reported; no case of ischemia driven TLR was detected. The total
      MACE-free survival probability was 66.5%. CONCLUSION: EPC capture stent
      implantation in high-risk patients requiring undeferrable non-cardiac surgery
      seems to allow early cand safe discontinuation of DAT, and may be an attractive
      alternative to conventional stents.

PMID- 21730939
TI  - Evaluation of nanoparticle uptake in tumors in real time using intravital
      imaging.
AB  - Current technologies for tumor imaging, such as ultrasound, MRI, PET and CT, are
      unable to yield high-resolution images for the assessment of nanoparticle uptake
      in tumors at the microscopic level(1,2,3,) highlighting the utility of a suitable
      xenograft model in which to perform detailed uptake analyses. Here, we use high
      resolution intravital imaging to evaluate nanoparticle uptake in human tumor
      xenografts in a modified, shell-less chicken embryo model. The chicken embryo
      model is particularly well-suited for these in vivo analyses because it supports
      the growth of human tumors, is relatively inexpensive and does not require
      anesthetization or surgery 4,5. Tumor cells form fully vascularized xenografts
      within 7 days when implanted into the chorioallantoic membrane (CAM)( 6). The
      resulting tumors are visualized by non-invasive real-time, high-resolution
      imaging that can be maintained for up to 72 hours with little impact on either
      the host or tumor systems. Nanoparticles with a wide range of sizes and
      formulations administered distal to the tumor can be visualized and quantified as
      they flow through the bloodstream, extravasate from leaky tumor vasculature, and
      accumulate at the tumor site. We describe here the analysis of nanoparticles
      derived from Cowpea mosaic virus (CPMV) decorated with near-infrared fluorescent
      dyes and/or polyethylene glycol polymers (PEG) (7, 8, 9,10,11). Upon intravenous
      administration, these viral nanoparticles are rapidly internalized by endothelial
      cells, resulting in global labeling of the vasculature both outside and within
      the tumor(7,12). PEGylation of the viral nanoparticles increases their plasma
      half-life, extends their time in the circulation, and ultimately enhances their
      accumulation in tumors via the enhanced permeability and retention (EPR) effect
      (7, 10,11). The rate and extent of accumulation of nanoparticles in a tumor is
      measured over time using image analysis software. This technique provides a
      method to both visualize and quantify nanoparticle dynamics in human tumors.

PMID- 21730940
TI  - A system for culturing iris pigment epithelial cells to study lens regeneration
      in newt.
AB  - Salamanders like newt and axolotl possess the ability to regenerate many of its
      lost body parts such as limbs, the tail with spinal cord, eye, brain, heart, the
      jaw1. Specifically, newts are unique for its lens regeneration capability. Upon
      lens removal, IPE cells of the dorsal iris transdifferentiate to lens cells and
      eventually form a new lens in about a month2(,)3 . This property of regeneration
      is never exhibited by the ventral iris cells. The regeneration potential of the
      iris cells can be studied by making transplants of the in vitro cultured IPE
      cells. For the culture, the dorsal and ventral iris cells are first isolated from
      the eye and cultured separately for a time period of 2 weeks (Figure 1). These
      cultured cells are reaggregated and implanted back to the newt eye. Past studies
      have shown that the dorsal reaggregate maintains its lens forming capacity
      whereas the ventral aggregate does not form a lens, recapitulating, thus the in
      vivo process (Figure 2)4(,)5. This system of determining regeneration potential
      of dorsal and ventral iris cells is very useful in studying the role of genes and
      proteins involved in lens regeneration.

PMID- 21730941
TI  - Preparation of living isolated vertebrate photoreceptor cells for fluorescence
      imaging.
AB  - In the vertebrate retina, phototransduction, the conversion of light to an
      electrical signal, is carried out by the rod and cone photoreceptor cells1-4. Rod
      photoreceptors are responsible for vision in dim light, cones in bright light.
      Phototransduction takes place in the outer segment of the photoreceptor cell, a
      specialized compartment that contains a high concentration of visual pigment, the
      primary light detector. The visual pigment is composed of a chromophore, 11-cis
      retinal, attached to a protein, opsin. A photon absorbed by the visual pigment
      isomerizes the chromophore from 11-cis to all-trans. This photoisomerization
      brings about a conformational change in the visual pigment that initiates a
      cascade of reactions culminating in a change in membrane potential, and bringing
      about the transduction of the light stimulus to an electrical signal. The
      recovery of the cell from light stimulation involves the deactivation of the
      intermediates activated by light, and the reestablishment of the membrane
      potential. Ca2+ modulates the activity of several of the enzymes involved in
      phototransduction, and its concentration is reduced upon light stimulation. In
      this way, Ca2+ plays an important role in the recovery of the cell from light
      stimulation and its adaptation to background light. Another essential part of the
      recovery process is the regeneration of the visual pigment that has been
      destroyed during light-detection by the photoisomerization of its 11-cis
      chromophore to all-trans5-7. This regeneration begins with the release of all
      trans retinal by the photoactivated pigment, leaving behind the apo-protein
      opsin. The released all-trans retinal is rapidly reduced in a reaction utilizing
      NADPH to all- trans retinol, and opsin combines with fresh 11-cis retinal brought
      into the outer segment to reform the visual pigment. All-trans retinol is then
      transferred out of the outer segment and into neighboring cells by the
      specialized carrier Interphotoreceptor Retinoid Binding Protein (IRBP).
      Fluorescence imaging of single photoreceptor cells can be used to study their
      physiology and cell biology. Ca2+-sensitive fluorescent dyes can be used to
      examine in detail the interplay between outer segment Ca2+ changes and response
      to light8-12 as well as the role of inner segment Ca2+ stores in Ca2+
      homeostasis13-14. Fluorescent dyes can also be used for measuring Mg2
      concentration15, pH, and as tracers of aqueous and membrane compartments16.
      Finally, the intrinsic fluorescence of all-trans retinol (vitamin A) can be used
      to monitor the kinetics of its formation and removal in single photoreceptor
      cells17-19.

PMID- 21730942
TI  - Development of cell-type specific anti-HIV gp120 aptamers for siRNA delivery.
AB  - The global epidemic of infection by HIV has created an urgent need for new
      classes of antiretroviral agents. The potent ability of small interfering
      (si)RNAs to inhibit the expression of complementary RNA transcripts is being
      exploited as a new class of therapeutics for a variety of diseases including HIV.
      Many previous reports have shown that novel RNAi-based anti-HIV/AIDS therapeutic
      strategies have considerable promise; however, a key obstacle to the successful
      therapeutic application and clinical translation of siRNAs is efficient delivery.
      Particularly, considering the safety and efficacy of RNAi-based therapeutics, it
      is highly desirable to develop a targeted intracellular siRNA delivery approach
      to specific cell populations or tissues. The HIV-1 gp120 protein, a glycoprotein
      envelope on the surface of HIV-1, plays an important role in viral entry into CD4
      cells. The interaction of gp120 and CD4 that triggers HIV-1 entry and initiates
      cell fusion has been validated as a clinically relevant anti-viral strategy for
      drug discovery. Herein, we firstly discuss the selection and identification of 2'
      F modified anti-HIV gp120 RNA aptamers. Using a conventional nitrocellulose
      filter SELEX method, several new aptamers with nanomolar affinity were isolated
      from a 50 random nt RNA library. In order to successfully obtain bound species
      with higher affinity, the selection stringency is carefully controlled by
      adjusting the conditions. The selected aptamers can specifically bind and be
      rapidly internalized into cells expressing the HIV-1 envelope protein.
      Additionally, the aptamers alone can neutralize HIV-1 infectivity. Based upon the
      best aptamer A-1, we also create a novel dual inhibitory function anti-gp120
      aptamer-siRNA chimera in which both the aptamer and the siRNA portions have
      potent anti-HIV activities. Further, we utilize the gp120 aptamer-siRNA chimeras
      for cell-type specific delivery of the siRNA into HIV-1 infected cells. This dual
      function chimera shows considerable potential for combining various nucleic acid
      therapeutic agents (aptamer and siRNA) in suppressing HIV-1 infection, making the
      aptamer-siRNA chimeras attractive therapeutic candidates for patients failing
      highly active antiretroviral therapy (HAART).

PMID- 21730943
TI  - Efficient gene delivery into multiple CNS territories using in utero
      electroporation.
AB  - The ability to manipulate gene expression is the cornerstone of modern day
      experimental embryology, leading to the elucidation of multiple developmental
      pathways. Several powerful and well established transgenic technologies are
      available to manipulate gene expression levels in mouse, allowing for the
      generation of both loss- and gain-of-function models. However, the generation of
      mouse transgenics is both costly and time consuming. Alternative methods of gene
      manipulation have therefore been widely sought. In utero electroporation is a
      method of gene delivery into live mouse embryos(1,2) that we have successfully
      adapted(3,4). It is largely based on the success of in ovo electroporation
      technologies that are commonly used in chick(5). Briefly, DNA is injected into
      the open ventricles of the developing brain and the application of an electrical
      current causes the formation of transient pores in cell membranes, allowing for
      the uptake of DNA into the cell. In our hands, embryos can be efficiently
      electroporated as early as embryonic day (E) 11.5, while the targeting of younger
      embryos would require an ultrasound-guided microinjection protocol, as previously
      described(6). Conversely, E15.5 is the latest stage we can easily electroporate,
      due to the onset of parietal and frontal bone differentiation, which hampers
      microinjection into the brain. In contrast, the retina is accessible through the
      end of embryogenesis. Embryos can be collected at any time point throughout the
      embryonic or early postnatal period. Injection of a reporter construct
      facilitates the identification of transfected cells. To date, in utero
      electroporation has been most widely used for the analysis of neocortical
      development(1,2,3,4). More recent studies have targeted the embryonic
      retina(7,8,9) and thalamus(10,11,12). Here, we present a modified in utero
      electroporation protocol that can be easily adapted to target different domains
      of the embryonic CNS. We provide evidence that by using this technique, we can
      target the embryonic telencephalon, diencephalon and retina. Representative
      results are presented, first showing the use of this technique to introduce DNA
      expression constructs into the lateral ventricles, allowing us to monitor
      progenitor maturation, differentiation and migration in the embryonic
      telencephalon. We also show that this technique can be used to target DNA to the
      diencephalic territories surrounding the 3(rd) ventricle, allowing the migratory
      routes of differentiating neurons into diencephalic nuclei to be monitored.
      Finally, we show that the use of micromanipulators allows us to accurately
      introduce DNA constructs into small target areas, including the subretinal space,
      allowing us to analyse the effects of manipulating gene expression on retinal
      development.

PMID- 21730944
TI  - In vivo electroporation of developing mouse retina.
AB  - The functional characterization of genes expressed during mammalian retinal
      development remains a significant challenge. Gene targeting to generate
      constitutive or conditional loss of function knockouts remains cost and labor
      intensive, as well as time consuming. Adding to these challenges, retina
      expressed genes may have essential roles outside the retina leading to unintended
      confounds when using a knockout approach. Furthermore, the ability to ectopically
      express a gene in a gain of function experiment can be extremely valuable when
      attempting to identify a role in cell fate specification and/or terminal
      differentiation. We present a method for the rapid and efficient incorporation of
      DNA plasmids into the neonatal mouse retina by electroporation. The application
      of short electrical impulses above a certain field strength results in a
      transient increase in plasma membrane permeability, facilitating the transfer of
      material across the membrane (1,2,3,4). Groundbreaking work demonstrated that
      electroporation could be utilized as a method of gene transfer into mammalian
      cells by inducing the formation of hydrophilic plasma membrane pores allowing the
      passage of highly charged DNA through the lipid bilayer (5). Continuous technical
      development has resulted in the viability of electroporation as a method for in
      vivo gene transfer in multiple mouse tissues including the retina, the method for
      which is described herein (6, 7, 8, 9, 10). DNA solution is injected into the
      subretinal space so that DNA is placed between the retinal pigmented epithelium
      and retina of the neonatal (P0) mouse and electrical pulses are applied using a
      tweezer electrode. The lateral placement of the eyes in the mouse allows for the
      easy orientation of the tweezer electrode to the necessary negative pole-DNA
      retina-positive pole alignment. Extensive incorporation and expression of
      transferred genes can be identified by postnatal day 2 (P2). Due to the lack of
      significant lateral migration of cells in the retina, electroporated and non
      electroporated regions are generated. Non-electroporated regions may serve as
      internal histological controls where appropriate. Retinal electroporation can be
      used to express a gene under a ubiquitous promoter, such as CAG, or to disrupt
      gene function using shRNA constructs or Cre-recombinase. More targeted expression
      can be achieved by designing constructs with cell specific gene promoters.
      Visualization of electroporated cells is achieved using bicistronic constructs
      expressing GFP or by co-electroporating a GFP expression construct. Furthermore,
      multiple constructs may be electroporated for the study of combinatorial gene
      effects or simultaneous gain and loss of function of different genes. Retinal
      electroporation may also be utilized for the analysis of genomic cis-regulatory
      elements by generating appropriate expression constructs and deletion mutants.
      Such experiments can be used to identify cis-regulatory regions sufficient or
      required for cell specific gene expression (11). Potential experiments are
      limited only by construct availability.

PMID- 21730945
TI  - Antimicrobial susceptibility testing of Mycobacterium tuberculosis complex for
      first and second line drugs by broth dilution in a microtiter plate format.
AB  - The rapid detection of antimicrobial resistance is important in the effort to
      control the increase in resistant Mycobacterium tuberculosis (Mtb). Antimicrobial
      susceptibility testing (AST) of Mtb has traditionally been performed by the agar
      method of proportion or by macrobroth testing on an instrument such as the BACTEC
      (Becton Dickinson, Sparks, MD), VersaTREK (TREK Diagnostics, Cleveland, OH) or
      BacT/ALERT (bioMerieux, Hazelwood, MO). The agar proportion method, while
      considered the "gold" standard of AST, is labor intensive and requires
      calculation of resistance by performing colony counts on drug-containing agar as
      compared to drug-free agar. If there is >=1% growth on the drug-containing medium
      as compared to drug-free medium, the organism is considered resistant to that
      drug. The macrobroth methods require instrumentation and test break point
      ("critical") drug concentrations for the first line drugs (isoniazid, ethambutol,
      rifampin, and pyrazinamide). The method described here is commercially available
      in a 96 well microtiter plate format [MYCOTB (TREK Diagnostics)] and contains
      increasing concentrations of 12 antimicrobials used for treatment of tuberculosis
      including both first (isoniazid, rifampin, ethambutol) and second line drugs
      (amikacin, cycloserine, ethionamide, kanamycin, moxifloxacin, ofloxacin, para
      aminosalicylic acid, rifabutin, and streptomycin). Pyrazinamide, a first line
      drug, is not included in the microtiter plate due to its need for acidic test
      conditions. Advantages of the microtiter system include both ease of set up and
      faster turn around time (14 days) compared with traditional agar proportion (21
      days). In addition, the plate can be set up from inoculum prepared using either
      broth or solid medium. Since the microtiter plate format is new and since Mtb
      presents unique safety challenges in the laboratory, this protocol will describe
      how to safely setup, incubate and read the microtiter plate.

PMID- 21730946
TI  - Ex vivo infection of live tissue with oncolytic viruses.
AB  - Oncolytic Viruses (OVs) are novel therapeutics that selectively replicate in and
      kill tumor cells(1). Several clinical trials evaluating the effectiveness of a
      variety of oncolytic platforms including HSV, Reovirus, and Vaccinia OVs as
      treatment for cancer are currently underway(2-5). One key characteristic of
      oncolytic viruses is that they can be genetically modified to express reporter
      transgenes which makes it possible to visualize the infection of tissues by
      microscopy or bio-luminescence imaging(6,7). This offers a unique advantage since
      it is possible to infect tissues from patients ex vivo prior to therapy in order
      to ascertain the likelihood of successful oncolytic virotherapy(8). To this end,
      it is critical to appropriately sample tissue to compensate for tissue
      heterogeneity and assess tissue viability, particularly prior to infection(9). It
      is also important to follow viral replication using reporter transgenes if
      expressed by the oncolytic platform as well as by direct titration of tissues
      following homogenization in order to discriminate between abortive and productive
      infection. The object of this protocol is to address these issues and herein
      describes 1. The sampling and preparation of tumor tissue for cell culture 2. The
      assessment of tissue viability using the metabolic dye alamar blue 3. Ex vivo
      infection of cultured tissues with vaccinia virus expressing either GFP or
      firefly luciferase 4. Detection of transgene expression by fluorescence
      microscopy or using an In Vivo Imaging System (IVIS) 5. Quantification of virus
      by plaque assay. This comprehensive method presents several advantages including
      ease of tissue processing, compensation for tissue heterogeneity, control of
      tissue viability, and discrimination between abortive infection and bone fide
      viral replication.

PMID- 21730947
TI  - Basic surgical techniques in the Gottingen minipig: intubation, bladder
      catheterization, femoral vessel catheterization, and transcardial perfusion.
AB  - The emergence of the Gottingen minipig in research of topics such as
      neuroscience, toxicology, diabetes, obesity, and experimental surgery reflects
      the close resemblance of these animals to human anatomy and physiology (1-6).The
      size of the Gottingen minipig permits the use of surgical equipment and advanced
      imaging modalities similar to those used in humans (6-8). The aim of this
      instructional video is to increase the awareness on the value of minipigs in
      biomedical research, by demonstrating how to perform tracheal intubation,
      transurethral bladder catheterization, femoral artery and vein catheterization,
      as well as transcardial perfusion. Endotracheal Intubation should be performed
      whenever a minipig undergoes general anesthesia, because it maintains a patent
      airway, permits assisted ventilation and protects the airways from aspirates.
      Transurethral bladder catheterization can provide useful information about about
      hydration state as well as renal and cardiovascular function during long surgical
      procedures. Furthermore, urinary catheterization can prevent contamination of
      delicate medico-technical equipment and painful bladder extension which may harm
      the animal and unnecessarily influence the experiment due to increased vagal tone
      and altered physiological parameters. Arterial and venous catheterization is
      useful for obtaining repeated blood samples and monitoring various physiological
      parameters. Catheterization of femoral vessels is preferable to catheterization
      of the neck vessels for ease of access, when performing experiments involving
      frame-based stereotaxic neurosurgery and brain imaging. When performing vessel
      catheterization in survival studies, strict aseptic technique must be employed to
      avoid infections(6). Transcardial perfusion is the most effective fixation
      method, and yields preeminent results when preparing minipig organs for histology
      and histochemistry(2,9). For more information about anesthesia, surgery and
      experimental techniques in swine in general we refer to Swindle 2007.
      Supplementary information about premedication and induction of anesthesia,
      assisted ventilation, analgesia, pre- and postoperative care of Gottingen
      minipigs are available via the internet at http://www.minipigs.com(10). For
      extensive information about porcine anatomy we refer to Nickel et al. Vol. 1
      5(11).

PMID- 21730948
TI  - Live imaging of cell extrusion from the epidermis of developing zebrafish.
AB  - Homeostatic maintenance of epithelial tissues requires the continual removal of
      damaged cells without disrupting barrier function. Our studies have found that
      dying cells send signals to their live neighbors to form and contract a ring of
      actin and myosin that ejects it out from the epithelial sheet while closing any
      gaps that might have resulted from its exit, a process termed cell extrusion1.
      The optical clarity of developing zebrafish provides an excellent system to
      visualize extrusion in living epithelia. Here we describe a method to induce and
      image extrusion in the larval zebrafish epidermis. To visualize extrusion, we
      inject a red fluorescent protein labeled probe for F-actin into one-cell stage
      transgenic zebrafish embryos expressing green fluorescent protein in the
      epidermis and induce apoptosis by addition of G418 to larvae. We then use time
      lapse imaging on a spinning disc confocal microscope to observe actin dynamics
      and epithelial cell behaviors during the process of apoptotic cell extrusion.
      This approach allows us to investigate the extrusion process in live epithelia
      and will provide an avenue to study disease states caused by the failure to
      eliminate apoptotic cells.

PMID- 21730949
TI  - A cell free assay system estimating the neutralizing capacity of GM-CSF antibody
      using recombinant soluble GM-CSF receptor.
AB  - BACKGROUNDS: Previously, we demonstrated that neutralizing capacity but not the
      concentration of GM-CSF autoantibody was correlated with the disease severity in
      patients with autoimmune pulmonary alveolar proteinosis (PAP)1-3. As abrogation
      of GM-CSF bioactivity in the lung is the likely cause for autoimmune PAP4-5, it
      is promising to measure the neutralizing capacity of GM-CSF autoantibodies for
      evaluating the disease severity in each patient with PAP. Until now, neutralizing
      capacity of GM-CSF autoantibodies has been assessed by evaluating the growth
      inhibition of human bone marrow cells or TF-1 cells stimulated with GM-CSF6-8. In
      the bioassay system, however, it is often problematic to obtain reliable data as
      well as to compare the data from different laboratories, due to the technical
      difficulties in maintaining the cells in a constant condition. OBJECTIVE: To
      mimic GM-CSF binding to GM-CSF receptor on the cell surface using cell-free
      receptor-binding-assay. METHODS: Transgenic silkworm technology was applied for
      obtaining a large amount for recombinant soluble GM-CSF receptor alpha
      (sGMRalpha) with high purity9-13. The recombinant sGMRalpha was contained in the
      hydrophilic sericin layers of silk threads without being fused to the silk
      proteins, and thus, we can easily extract from the cocoons in good purity with
      neutral aqueous solutions14(,)15. Fortunately, the oligosaccharide structures,
      which are critical for binding with GM-CSF, are more similar to the structures of
      human sGMRalpha than those produced by other insects or yeasts. RESULTS: The cell
      free assay system using sGMRalpha yielded the data with high plasticity and
      reliability. GM-CSF binding to sGMRalpha was dose-dependently inhibited by
      polyclonal GM-CSF autoantibody in a similar manner to the bioassay using TF-1
      cells, indicating that our new cell-free assay system using sGMRalpha is more
      useful for the measurement of neutralizing activity of GM-CSF autoantibodies than
      the bioassay system using TF-1 cell or human bone marrow cells. CONCLUSIONS: We
      established a cell-free assay quantifying the neutralizing capacity of GM-CSF
      autoantibody.

PMID- 21730950
TI  - Investigating social cognition in infants and adults using dense array
      electroencephalography ((d)EEG).
AB  - Dense array electroencephalography ((d)EEG), which provides a non-invasive window
      for measuring brain activity and a temporal resolution unsurpassed by any other
      current brain imaging technology1, 2 is being used increasingly in the study of
      social cognitive functioning in infants and adults. While (d)EEG is enabling
      researchers to examine brain activity patterns with unprecedented levels of
      sensitivity, conventional EEG recording systems continue to face certain
      limitations, including 1) poor spatial resolution and source localization3,42)
      the physical discomfort for test subjects of enduring the individual application
      of numerous electrodes to the surface of the scalp, and 3) the complexity for
      researchers of learning to use multiple software packages to collect and process
      data. Here we present an overview of an established methodology that represents a
      significant improvement on conventional methodologies for studying EEG in infants
      and adults. Although several analytical software techniques can be used to
      establish indirect indices of source localization to improve the spatial
      resolution of (d)EEG, the HydroCel Geodesic Sensor Net (HCGSN) by Electrical
      Geodesics, Inc. (EGI), a dense sensory array that maintains equal distances among
      adjacent recording electrodes on all surfaces of the scalp, further enhances
      spatial resolution4,5(,)6 compared to standard (d)EEG systems. The sponge-based
      HCGSN can be applied rapidly and without scalp abrasion, making it ideal for use
      with adults7,8 children9,10, 11,12 and infants12, in both research and clinical
      4,5,6,13,14,15settings. This feature allows for considerable cost and time
      savings by decreasing the average net application time compared to other (d)EEG
      systems. Moreover, the HCGSN includes unified, seamless software applications for
      all phases of data, greatly simplifying the collection, processing, and analysis
      of (d)EEG data. The HCGSN features a low-profile electrode pedestal, which, when
      filled with electrolyte solution, creates a sealed microenvironment and an
      electrode-scalp interface. In all Geodesic (d;)EEG systems, EEG sensors detect
      changes in voltage originating from the participant's scalp, along with a small
      amount of electrical noise originating from the room environment. Electrical
      signals from all sensors of the Geodesic sensor net are received simultaneously
      by the amplifier, where they are automatically processed, packaged, and sent to
      the data-acquisition computer (DAC). Once received by the DAC, scalp electrical
      activity can be isolated from artifacts for analysis using the filtering and
      artifact detection tools included in the EGI software. Typically, the HCGSN can
      be used continuously for only up to two hours because the electrolyte solution
      dries out over time, gradually decreasing the quality of the scalp-electrode
      interface. In the Parent-Infant Research Lab at the University of Toronto, we are
      using (d)EEG to study social cognitive processes including memory, emotion,
      goals, intentionality, anticipation, and executive functioning in both adult and
      infant participants.

PMID- 21730951
TI  - Microwave-assisted one-pot synthesis of N-succinimidyl-4[ 18F]fluorobenzoate
      ([18F]SFB).
AB  - Biomolecules, including peptides1-9, proteins10-11, and antibodies and their
      engineered fragments12-14, are gaining importance as both potential therapeutics
      and molecular imaging agents. Notably, when labeled with positron-emitting
      radioisotopes (e.g., Cu-64, Ga-68, or F-18), they can be used as probes for
      targeted imaging of many physiological and pathological processes.15-18
      Therefore, significant effort has devoted to the synthesis and exploration of 18F
      labeled biomolecules. Although there are elegant examples of the direct 18F
      labeling of peptides,19-22 the harsh reaction conditions (i.e., organic solvent,
      extreme pH, high temperature) associated with direct radiofluorination are
      usually incompatible with fragile protein samples. To date, therefore, the
      incorporation of radiolabeled prosthetic groups into biomolecules remains the
      method of choice.23(,)24 N-Succinimidyl-4-[18F]fluorobenzoate ([18F]SFB),25-37 a
      Bolton-Hunter type reagent that reacts with the primary amino groups of
      biomolecules, is a very versatile prosthetic group for the 18F-labeling of a wide
      spectrum of biological entities, in terms of its evident in vivo stability and
      high radiolabeling yield. After labeling with [18F]SFB, the resulting
      [F]fluorobenzoylated biomolecules could be explored as potential PET tracers for
      in vivo imaging studies.1 Most [18F]SFB radiosyntheses described in the current
      literatures require two or even three reactors and multiple purifications by
      using either solid phase extraction (SPE) or high-performance liquid
      chromatography (HPLC). Such lengthy processes hamper its routine production and
      widespread applications in the radiolabeling of biomolecules. Although several
      module-assisted [18F]SFB syntheses have been reported29-32,41-42 they are mainly
      based on complicated and lengthy procedures using costly commercially-available
      radiochemistry boxes (Table 1). Therefore, further simplification of the
      radiosynthesis of [18F]SFB using a low-cost setup would be very beneficial for
      its adaption to an automated process. Herein, we report a concise preparation of
      [18F]SFB, based on a simplified one-pot microwave-assisted synthesis (Figure 1).
      Our approach does not require purification between steps or any aqueous reagents.
      In addition, microwave irradiation, which has been used in the syntheses of
      several PET tracers,38-41 can gives higher RCYs and better selectivity than the
      corresponding thermal reactions or they provide similar yields in shorter
      reaction times.38Most importantly, when labeling biomolecules, the time saved
      could be diverted to subsequent bioconjugation or PET imaging step. 28(,)43The
      novelty of our improved [18F]SFB synthesis is two-fold: (1) the anhydrous
      deprotection strategy requires no purification of intermediate(s) between each
      step and (2) the microwave-assisted radiochemical transformations enable the
      rapid, reliable production of [18F]SFB.

PMID- 21730952
TI  - Quantifying the activity of cis-regulatory elements in the mouse retina by
      explant electroporation.
AB  - Transcription factors within cellular gene networks control the spatiotemporal
      pattern and levels of expression of their target genes by binding to cis
      regulatory elements (CREs), short (~300-600 bp) stretches of genomic DNA which
      can lie upstream, downstream, or within the introns of the genes they control.
      CREs (i.e., enhancers/promoters) typically consist of multiple clustered binding
      sites for both transcriptional activators and repressors(1-3). They serve as
      logical integrators of transcriptional input giving a unitary output in the form
      of spatiotemporally precise and quantitatively exact promoter activity. Most
      studies of mammalian cis-regulation to date have relied on mouse transgenesis as
      a means of assaying the enhancer function of CREs(4-5). This technique is time
      consuming, costly and, on account of insertion site effects, largely non
      quantitative. On the other hand, quantitative assays for mammalian CRE function
      have been developed in tissue culture systems (e.g., dual luciferase assays), but
      the in vivo relevance of these results is often uncertain. Electroporation offers
      an excellent alternative to traditional mouse transgenesis in that it permits
      both spatiotemporal and quantitative assessment of cis-regulatory activity in
      living mammalian tissue. This technique has been particularly useful in the
      analysis of cis-regulation in the central nervous system, especially in the
      cerebral cortex and the retina(6-8). While mouse retinal electroporation, both in
      vivo and ex vivo, has been developed and extensively described by Matsuda and
      Cepko(6-7,9), we have recently developed a simple approach to quantify the
      activity of photoreceptor-specific CREs in electroporated mouse retinas(10).
      Given that the amount of DNA that is introduced into the retina by
      electroporation can vary from experiment to experiment, it is necessary to
      include a co-electroporated 'loading control' in all experiments. In this
      respect, the technique is very similar to the dual luciferase assay used to
      quantify promoter activity in cultured cells. When assaying photoreceptor cis
      regulatory activity, electroporation is usually performed in newborn mice
      (postnatal day 0, P0) which is the time of peak rod production(11-12). Once
      retinal cell types become post-mitotic, electroporation is much less efficient.
      Given the high rate of rod birth in newborn mice and the fact that rods
      constitute more than 70% of the cells in the adult mouse retina, the majority of
      cells that are electroporated at P0 are rods. For this reason, rod photoreceptors
      are the easiest retinal cell type to study via electroporation. The technique we
      describe here is primarily useful for quantifying the activity of photoreceptor
      CREs.

PMID- 21730953
TI  - Photobleaching assays (FRAP & FLIP) to measure chromatin protein dynamics in
      living embryonic stem cells.
AB  - Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Loss In
      Photobleaching (FLIP) enable the study of protein dynamics in living cells with
      good spatial and temporal resolution. Here we describe how to perform FRAP and
      FLIP assays of chromatin proteins, including H1 and HP1, in mouse embryonic stem
      (ES) cells. In a FRAP experiment, cells are transfected, either transiently or
      stably, with a protein of interest fused with the green fluorescent protein (GFP)
      or derivatives thereof (YFP, CFP, Cherry, etc.). In the transfected, fluorescing
      cells, an intense focused laser beam bleaches a relatively small region of
      interest (ROI). The laser wavelength is selected according to the fluorescent
      protein used for fusion. The laser light irreversibly bleaches the fluorescent
      signal of molecules in the ROI and, immediately following bleaching, the recovery
      of the fluorescent signal in the bleached area - mediated by the replacement of
      the bleached molecules with the unbleached molecules - is monitored using time
      lapse imaging. The generated fluorescence recovery curves provide information on
      the protein's mobility. If the fluorescent molecules are immobile, no
      fluorescence recovery will be observed. In a complementary approach, Fluorescence
      Loss in Photobleaching (FLIP), the laser beam bleaches the same spot repeatedly
      and the signal intensity is measured elsewhere in the fluorescing cell. FLIP
      experiments therefore measure signal decay rather than fluorescence recovery and
      are useful to determine protein mobility as well as protein shuttling between
      cellular compartments. Transient binding is a common property of chromatin
      associated proteins. Although the major fraction of each chromatin protein is
      bound to chromatin at any given moment at steady state, the binding is transient
      and most chromatin proteins have a high turnover on chromatin, with a residence
      time in the order of seconds. These properties are crucial for generating high
      plasticity in genome expression1. Photobleaching experiments are therefore
      particularly useful to determine chromatin plasticity using GFP-fusion versions
      of chromatin structural proteins, especially in ES cells, where the dynamic
      exchange of chromatin proteins (including heterochromatin protein 1 (HP1), linker
      histone H1 and core histones) is higher than in differentiated cells. 2 (,)3

PMID- 21730954
TI  - Activation of apoptosis by cytoplasmic microinjection of cytochrome c.
AB  - Apoptosis, or programmed cell death, is a conserved and highly regulated pathway
      by which cells die1. Apoptosis can be triggered when cells encounter a wide range
      of cytotoxic stresses. These insults initiate signaling cascades that ultimately
      cause the release of cytochrome c from the mitochondrial intermembrane space to
      the cytoplasm2. The release of cytochrome c from mitochondria is a key event that
      triggers the rapid activation of caspases, the key cellular proteases which
      ultimately execute cell death3-4. The pathway of apoptosis is regulated at points
      upstream and downstream of cytochrome c release from mitochondria5. In order to
      study the post-mitochondrial regulation of caspase activation, many investigators
      have turned to direct cytoplasmic microinjection of holocytochrome c (heme
      attached) protein into cells6-9. Cytochrome c is normally localized to the
      mitochondria where attachment of a heme group is necessary to enable it to
      activate apoptosis10-11. Therefore, to directly activate caspases, it is
      necessary to inject the holocytochrome c protein instead of its cDNA, because
      while the expression of cytochrome c from cDNA constructs will result in
      mitochondrial targeting and heme attachment, it will be sequestered from
      cytosolic caspases. Thus, the direct cytosolic microinjection of purified heme
      attached cytochrome c protein is a useful tool to mimic mitochondrial cytochrome
      c release and apoptosis without the use of toxic insults which cause cellular and
      mitochondrial damage. In this article, we describe a method for the
      microinjection of cytochrome c protein into cells, using mouse embryonic
      fibroblasts (MEFs) and primary sympathetic neurons as examples. While this
      protocol focuses on the injection of cytochrome c for investigations of
      apoptosis, the techniques shown here can also be easily adapted for
      microinjection of other proteins of interest.

PMID- 21730955
TI  - Experimental coevolution of male and female genital morphology.
AB  - Male genitalia typically exhibit patterns of rapid and divergent evolution, and
      there is now considerable evidence that sexual selection is an important driver
      of these patterns of phenotypic variation. Female genitalia have been less well
      studied, and are generally thought to be relatively invariant. Here we use
      experimental evolution to show that sexual selection drives the correlated
      evolution of female and male genital morphology in the scarabaeine dung beetle
      Onthophagus taurus. Moreover, we use quantitative genetic analyses to provide a
      rare insight into the genetic architecture underlying morphological variation in
      female genital morphology, and uncover evidence of the genetic covariation with
      male genital morphology that is expected to arise under persistent sexual
      selection.

PMID- 21730956
TI  - Identification and characterization of a multidomain hyperthermophilic cellulase
      from an archaeal enrichment.
AB  - Despite extensive studies on microbial and enzymatic lignocellulose degradation,
      relatively few Archaea are known to deconstruct crystalline cellulose. Here we
      describe a consortium of three hyperthermophilic archaea enriched from a
      continental geothermal source by growth at 90  degrees C on crystalline
      cellulose, representing the first instance of Archaea able to deconstruct
      lignocellulose optimally above 90  degrees C. Following metagenomic studies on
      the consortium, a 90 kDa, multidomain cellulase, annotated as a member of the TIM
      barrel glycosyl hydrolase superfamily, was characterized. The multidomain
      architecture of this protein is uncommon for hyperthermophilic endoglucanases,
      and two of the four domains of the enzyme have no characterized homologues. The
      recombinant enzyme has optimal activity at 109  degrees C, a half-life of 5 h at
      100  degrees C, and resists denaturation in strong detergents, high-salt
      concentrations, and ionic liquids. Cellulases active above 100  degrees C may
      assist in biofuel production from lignocellulosic feedstocks by hydrolysing
      cellulose under conditions typically employed in biomass pretreatment.

PMID- 21730957
TI  - Tonic excitation or inhibition is set by GABA(A) conductance in hippocampal
      interneurons.
AB  - Inhibition is a physiological process that decreases the probability of a neuron
      generating an action potential. The two main mechanisms that have been proposed
      for inhibition are hyperpolarization and shunting. Shunting results from
      increased membrane conductance, and it reduces the neuron-firing probability.
      Here we show that ambient GABA, the main inhibitory neurotransmitter in the
      brain, can excite adult hippocampal interneurons. In these cells, the GABA(A)
      current reversal potential is depolarizing, making baseline tonic GABA(A)
      conductance excitatory. Increasing the tonic conductance enhances shunting
      mediated inhibition, which eventually overpowers the excitation. Such a biphasic
      change in interneuron firing leads to corresponding changes in the GABA(A)
      mediated synaptic signalling. The described phenomenon suggests that the
      excitatory or inhibitory actions of the current are set not only by the reversal
      potential, but also by the conductance.

PMID- 21730958
TI  - Onset of a quantum phase transition with a trapped ion quantum simulator.
AB  - A quantum simulator is a well-controlled quantum system that can follow the
      evolution of a prescribed model whose behaviour may be difficult to determine. A
      good example is the simulation of a set of interacting spins, where phase
      transitions between various spin orders can underlie poorly understood concepts
      such as spin liquids. Here we simulate the emergence of magnetism by implementing
      a fully connected non-uniform ferromagnetic quantum Ising model using up to 9
      trapped (171)Yb(+) ions. By increasing the Ising coupling strengths compared with
      the transverse field, the crossover from paramagnetism to ferromagnetic order
      sharpens as the system is scaled up, prefacing the expected quantum phase
      transition in the thermodynamic limit. We measure scalable order parameters
      appropriate for large systems, such as various moments of the magnetization. As
      the results are theoretically tractable, this work provides a critical benchmark
      for the simulation of intractable arbitrary fully connected Ising models in
      larger systems.

PMID- 21730959
TI  - Using disorder to detect locally ordered electron nematics via hysteresis.
AB  - The interplay between charge, orbital and lattice degrees of freedom in
      correlated electron systems has resulted in many proposals for new electronic
      phases of matter. An electron nematic breaks the point group symmetry of the host
      crystal, often from C(6) or C(4) rotational symmetry to C(2). Electron nematics
      have been reported in several condensed matter systems including cuprate- and
      iron arsenic-based high-temperature superconductors, and they have been proposed
      to exist in many other materials. However, the combination of reduced
      dimensionality and material disorder typically limits the spatial range over
      which electron nematic order persists, rendering its experimental detection
      extremely difficult. Despite the tantalizing possible connection between the
      phase and high-temperature superconductivity, there is surprisingly little
      guidance in the literature about how to detect the remaining disordered electron
      nematic. Here we propose two protocols for detecting disordered electron nematics
      in condensed matter systems using non-equilibrium methods.

PMID- 21730960
TI  - Identification of the PGRMC1 protein complex as the putative sigma-2 receptor
      binding site.
AB  - The sigma-2 receptor, whose gene remains to be cloned, has been validated as a
      biomarker for tumour cell proliferation. Here we report the use of a novel
      photoaffinity probe, WC-21, to identify the sigma-2 receptor-binding site. WC-21,
      a sigma-2 ligand containing both a photoactive azide moiety and a fluorescein
      isothiocyanate group, irreversibly labels sigma-2 receptors in rat liver; the
      membrane-bound protein was identified as PGRMC1 (progesterone receptor membrane
      component 1). Immunocytochemistry reveals that both PGRMC1 and SW120, a
      fluorescent sigma-2 receptor ligand, colocalize with molecular markers of the
      endoplasmic reticulum and mitochondria in HeLa cells. Overexpression and
      knockdown of the PGRMC1 protein results in an increase and a decrease in binding
      of a sigma-2 selective radioligand, respectively. The identification of the
      putative sigma-2 receptor-binding site as PGRMC1 should stimulate the development
      of unique imaging agents and cancer therapeutics that target the sigma-2
      receptor/PGRMC1 complex.

PMID- 21730961
TI  - Hierarchical MnMoO(4)/CoMoO(4) heterostructured nanowires with enhanced
      supercapacitor performance.
AB  - Recent attention has been focused on the synthesis and application of complex
      heterostructured nanomaterials, which can have superior electrochemical
      performance than single-structured materials. Here we synthesize the three
      dimensional (3D) multicomponent oxide, MnMoO(4)/CoMoO(4). Hierarchical
      heterostructures are successfully prepared on the backbone material MnMoO(4) by a
      simple refluxing method under mild conditions; and surface modification is
      achieved. We fabricate asymmetric supercapacitors based on hierarchical
      MnMoO(4)/CoMoO(4) heterostructured nanowires, which show a specific capacitance
      of 187.1 F g(-1) at a current density of 1 A g(-1), and good reversibility with a
      cycling efficiency of 98% after 1,000 cycles. These results further demonstrate
      that constructing 3D hierarchical heterostructures can improve electrochemical
      properties. 'Oriented attachment' and 'self-assembly' crystal growth mechanisms
      are proposed to explain the formation of the heterostructures.

PMID- 21730962
TI  - Optical switching of nuclear spin-spin couplings in semiconductors.
AB  - Two-qubit operation is an essential part of quantum computation. However, solid
      state nuclear magnetic resonance quantum computing has not been able to fully
      implement this functionality, because it requires a switchable inter-qubit
      coupling that controls the time evolutions of entanglements. Nuclear dipolar
      coupling is beneficial in that it is present whenever nuclear-spin qubits are
      close to each other, while it complicates two-qubit operation because the qubits
      must remain decoupled to prevent unwanted couplings. Here we introduce optically
      controllable internuclear coupling in semiconductors. The coupling strength can
      be adjusted externally through light power and even allows on/off switching. This
      feature provides a simple way of switching inter-qubit couplings in semiconductor
      based quantum computers. In addition, its long reach compared with nuclear
      dipolar couplings allows a variety of options for arranging qubits, as they need
      not be next to each other to secure couplings.

PMID- 21730963
TI  - Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone
      deacetylase complex RPD3L.
AB  - TORC1 is a conserved multisubunit kinase complex that regulates many aspects of
      eukaryotic growth including the biosynthesis of ribosomes. The TOR protein kinase
      resident in TORC1 is responsive to environmental cues and is potently inhibited
      by the natural product rapamycin. Recent characterization of the rapamycin
      sensitive phosphoproteome in yeast has yielded insights into how TORC1 regulates
      growth. Here, we show that Sch9, an AGC family kinase and direct substrate of
      TORC1, promotes ribosome biogenesis (Ribi) and ribosomal protein (RP) gene
      expression via direct inhibitory phosphorylation of the transcriptional
      repressors Stb3, Dot6 and Tod6. Deletion of STB3, DOT6 and TOD6 partially
      bypasses the growth and cell size defects of an sch9 strain and reveals
      interdependent regulation of both Ribi and RP gene expression, and other aspects
      of Ribi. Dephosphorylation of Stb3, Dot6 and Tod6 enables recruitment of the
      RPD3L histone deacetylase complex to repress Ribi/RP gene promoters. Taken
      together with previous studies, these results suggest that Sch9 is a master
      regulator of ribosome biogenesis through the control of Ribi, RP, ribosomal RNA
      and tRNA gene transcription.

PMID- 21730964
TI  - Assessment of epicardial fat volume and myocardial triglyceride content in
      severely obese subjects: relationship to metabolic profile, cardiac function and
      visceral fat.
AB  - OBJECTIVE: To assess epicardial fat volume (EFV), myocardial TG content (MTGC)
      and metabolic profile in severely obese patients, and to determine whether
      ectopic fat depots are linked to metabolic disorders or myocardial function.
      RESEARCH DESIGN AND METHODS: Sixty-three subjects with normal LV function and no
      coronary artery disease, including 33 lean (BMI: 21.4 +/- 2.0 kg m(-2)) and 30
      obese (BMI: 41.8 +/- 6 kg m(-2)) patients, underwent 3-T cardiovascular MRI, and
      anthropometric, biological and visceral abdominal fat (VAT) assessments. EFV was
      measured by short-axis slice imaging and myocardial (intra-myocellular) TG
      content was measured by proton magnetic resonance spectroscopy. RESULTS: EFV and
      MTGC were positively correlated (r=0.52, P<0.0001), and were both strongly
      correlated with age, BMI, waist circumference and VAT, but not with severity of
      obesity. EFV and MTGC were significantly higher in obese patients than in lean
      controls (141 +/- 18 versus 79 +/- 7 ml, P=0.0001; 1.0 +/- 0.1 versus 0.6 +/-
      0.1%, P=0.01, respectively), but some differences were found between the two
      cardiac depots: EFV was higher in diabetic obese subjects as compared with that
      in non-diabetic obese subjects (213 +/- 34 versus 141 +/- 18 ml, P=0.03), and was
      correlated with parameters of glucose tolerance (fasting plasma glucose, insulin
      and HOMA-IR), whereas MTGC was not. EFV and MTGC were both associated with
      parameters of lipid profile or inflammation (TGs, CRP). Remarkably, this was VAT
      dependent, as only VAT remained independently associated with metabolic
      parameters (P<0.01). Concerning myocardial function, MTGC was the only parameter
      independently associated with stroke volume (beta=-0.38, P=0.01), suggesting an
      impact of cardiac steatosis in cardiac function. CONCLUSIONS: These data show
      that VAT dominates the relationship between EFV, MTGC and metabolic measures, and
      uncover specific partitioning of cardiac ectopic lipid deposition.

PMID- 21730965
TI  - Body composition changes after laparoscopic adjustable gastric banding: what is
      the role of -174G>C interleukin-6 promoter gene polymorphism in the therapeutic
      strategy?
AB  - BACKGROUND: There is growing evidence that interleukin-6 (IL-6) is linked to the
      regulation of fat mass (FM). Our previous data define the common -174G>C IL-6
      polymorphism as a marker for 'vulnerable' individuals at risk of age- and obesity
      related diseases. An association between -174G>C IL-6 polymorphism and weight
      loss after bariatric surgery has been demonstrated. OBJECTIVE: We investigated
      the impact of -174G>C IL-6 polymorphism on weight loss, body composition, fluid
      distribution and cardiometabolic changes in obese subjects, after laparoscopic
      adjustable gastric banding (LAGB) surgery. DESIGN AND OUTCOME MEASURES: A total
      of 40 obese subjects were studied at baseline and at 6 months follow-up after
      LAGB surgery. Cardiometabolic and genetic assessment of -174G>C IL-6
      polymorphism, anthropometric, body composition and fluid distribution analysis
      were performed. RESULTS: After LAGB surgery, significant reductions in weight
      (Delta%=-11.66 +/- 7.78, P<0.001), body mass index (P<0.001), total and trunk FM
      (kg, %) (Delta% of total FM=-22.22 +/- 12.15, P<0.01), bone mineral density (T
      score) (P<0.001), resting metabolic rate (RMR) (P<0.01), and total body water and
      intracellular water (TBW, ICW) (P<0.05) were observed. At baseline, C(-) carriers
      of IL-6 polymorphism had a significantly higher RMR (P<0.05), free FM (kg), but
      less total and trunk FM (%), higher body cell mass (BCM), content of TBW (L) and
      ECW (extracellular water)/ICW ratio compared with C(+) carriers (P<0.001). After
      LAGB, C(+) carriers had a significantly stronger reduction of total FM (kg), but
      lower bone density, compared with C(-) carriers (P<0.05). CONCLUSIONS: Beyond the
      relationship between -174G>C IL-6 polymorphism and body composition, this study
      provides first evidence about the association of IL-6 variant with fluid
      distribution, at baseline, and FM and bone density loss in obese subjects at 6
      months follow-up after LAGB surgery. LAGB was less effective if the subjects were
      carrying risk genotypes, C(-) carriers, for obesity, suggesting a role of genetic
      variations on bariatric surgery outcomes.

PMID- 21730966
TI  - Emerging disparities in overweight by educational attainment in Chinese adults
      (1989-2006).
AB  - OBJECTIVE: To test whether a disparity in overweight by socioeconomic status
      (SES; represented by educational attainment) has emerged among men or women
      during a recent 17-year period in China. METHODS: Data from the China Health and
      Nutrition Survey (CHNS), a panel study including 7314 women and 6492 men, are
      used to longitudinally track the body mass index (BMI) and odds of overweight by
      educational attainment among Chinese adults (baseline age 18-50) from 1989 to
      2006 to determine whether individuals of low (<primary school) versus high
      (>secondary school) educational attainment experienced a disproportionately
      faster increase in BMI or odds of overweight (BMI>=25) over time. The unadjusted
      mean BMI and prevalence of overweight by education are presented. Sex-stratified,
      random-effects models are used to estimate the associations, and interactions by
      birth cohort are included. FINDINGS: Overweight prevalence doubled for women and
      tripled for men. In 1989, among women, the odds of overweight were not different
      for those of high versus those of low educational attainment; however, by 2006,
      the odds of overweight were significantly lower for those with the highest
      education in both the younger (odds ratio (OR) 0.22 (CI 0.11, 0.42)) and the
      older (OR 0.27 (CI 0.10, 0.72)) birth cohorts. The reverse trend is seen for men,
      who also begin with no difference in odds of overweight by SES, but by 2006, the
      OR for the highest versus the lowest education group was 3.4 (CI 1.82, 6.18).
      CONCLUSIONS: Over 17 years, low SES has become associated with higher BMI and
      odds of overweight among Chinese women, whereas high SES remains a risk factor
      for overweight among Chinese men.

PMID- 21730967
TI  - Effects of a high-fat diet during pregnancy and lactation are modulated by E.
      coli in rat offspring.
AB  - OBJECTIVE: Microbial manipulations in early life can affect gut development and
      inflammatory status of the neonate. The maternal diet during pregnancy and
      lactation also influences the health of the offspring, but the impact of maternal
      high-fat (HF) feeding along with modulations of the gut microbiota on body
      weight, fat deposition and gut function in the offspring has been poorly studied.
      METHODS: Rat dams were given access to either an HF or a standard low-fat diet
      during the last 2 weeks of pregnancy and during lactation and effects on body
      weight and gastrointestinal function were investigated in the 14-day-old
      offspring. To elucidate whether bacterial administration to the dam could
      modulate any effects of the diets in the rat pups, another group of dams were
      given Escherichia coli in their drinking water. RESULTS: Maternal HF feeding
      resulted in increased body and fat pad weights in the offspring, along with
      increased levels of the acute-phase protein, haptoglobin and decreased protein
      content and disaccharidase activities in the small intestine. The addition of E.
      coli further accentuated these responses in the young rats, which, in addition to
      higher body weights and increased fat deposition, also showed an increased
      intestinal permeability and elevated levels of haptoglobin. CONCLUSIONS: The
      present study demonstrates for the first time how bacterial administration to the
      maternal diet during the neonatal period can affect body weight and fat
      deposition in the offspring. The results point to a mechanistic link between the
      gut microbiota, increased intestinal permeability and metabolic endotoxemia,
      which appear to have led to increased adiposity in the young rats.

PMID- 21730968
TI  - Contrasting effects of A1 and A2b adenosine receptors on adipogenesis.
AB  - BACKGROUND: Adenosine mediates its actions through four G protein-coupled
      receptors, A1, A2a, A2b and A3. The A1 receptor (A1R) is dominant in adipocytes
      where it mediates many actions that include inhibition of lipolysis, stimulation
      of leptin secretion and protection against obesity-related insulin resistance.
      OBJECTIVE: The objective of this study is to investigate whether induced
      expression of A1Rs stimulates adipogenesis, or whether A1R expression is a
      consequence of cells having an adipocyte phenotype. METHODOLOGY: Human A1R and
      A2b receptors (A2bRs) were stably transfected into a murine osteoblast precursor
      cell line, 7F2. Adipogenesis was determined by lipid accumulation and expression
      of adipocyte and osteoblast marker molecules. Adenosine receptor expression and
      activation of associated signal molecules were also evaluated as 7F2 cells were
      induced to differentiate to adipocytes. RESULTS: 7F2 cells transfected with the
      A1R showed increased adipocyte marker mRNA expression; lipoprotein lipase and
      glycerol-3-phosphate dehydrogenase were both upregulated, whereas the osteoblast
      marker alkaline phosphatase (ALP) was downregulated. When cultured in adipocyte
      differentiating media, such cells also showed increased adipogenesis as judged by
      lipid accumulation. Conversely, A2bR transfection stimulated osteocalcin and ALP
      expression, and in addition, adipogenesis was inhibited in the presence of
      adipocyte differentiation media. Adipogenic differentiation of naive 7F2 cells
      also resulted in increased expression of the A1R and reduced or modified
      expression of the A2a and A2bR. The loss of A2 receptors after adipogenic
      differentiation was accompanied by a loss of cyclic adenosine monophosphate and
      ERK1/2 signalling. CONCLUSION: These data show that expression of A1Rs induced
      adipocyte differentiation, whereas A2bR expression inhibited adipogenesis and
      stimulated an osteoblastic phenotype. These data suggest that targeting A1 and
      A2bR could be considered in the management of obesity and diabetes. Targeting
      adenosine signal pathways may be useful in treatment strategies for diseases in
      which there is an imbalance between osteoblasts and adipocytes.

PMID- 21730969
TI  - Large-volume intrathecal enzyme delivery increases survival of a mouse model of
      late infantile neuronal ceroid lipofuscinosis.
AB  - Late infantile neuronal ceroid lipofuscinosis (LINCL) is a progressive
      neurodegenerative lysosomal storage disorder caused by mutations in TPP1, the
      gene encoding the lysosomal protease tripeptidyl-peptidase (TPP1). LINCL
      primarily affects children, is fatal and there is no effective treatment.
      Administration of recombinant protein has proved effective in treatment of
      visceral manifestations of other lysosomal storage disorders but to date, only
      marginal improvement in survival has been obtained for neurological diseases. In
      this study, we have developed and optimized a large-volume intrathecal
      administration strategy to deliver therapeutic amounts of TPP1 to the central
      nervous system (CNS) of a mouse model of LINCL. To determine the efficacy of
      treatment, we have monitored survival as the primary endpoint and demonstrate
      that an acute treatment regimen (three consecutive daily doses started at 4 weeks
      of age) increases median lifespan of the LINCL mice from 16 (vehicle treated) to
      23 weeks (enzyme treated). Consistent with the increase in life-span, we also
      observed significant reversal of pathology and improvement in neurological
      phenotype. These results provide a strong basis for both clinical investigation
      of large-volume/high-dose delivery of TPP1 to the brain via the cerebrospinal
      fluid (CSF) and extension of this approach towards other neurological lysosomal
      storage diseases.

PMID- 21730970
TI  - Manipulating piggyBac transposon chromosomal integration site selection in human
      cells.
AB  - The ability to direct gene delivery to a user-defined chromosomal location would
      greatly improve gene transfer applications. The piggyBac transposon system is a
      nonviral gene transfer system proven effective in a variety of cells and tissues,
      including human cells. We fused a highly site-specific synthetic zinc-finger DNA
      binding domain (ZFP) to the N-terminus of the piggyBac transposase and evaluated
      site-directed genomic integration in human cells. Chimeric ZFP-piggyBac
      transposase exhibited robust gene transfer activity, targeted binding to a
      cognate endogenous chromosomal ZFP site in the human genome, and site-directed
      transposon integration into an episomal plasmid target containing a single ZFP
      site in human cells. We evaluated the ability of ZFP-piggyBac to direct gene
      integration into an engineered chromosomal ZFP target site in the human genome
      and consistently observed a higher degree of ZFP-piggyBac site-directed genomic
      integration when compared to native piggyBac. Chromatin immunoprecipitation
      (ChIP) experiments revealed binding of native piggyBac to our engineered TTAA
      containing chromosomal target which supported integration, but not a TTAA
      deficient chromosomal target which lacked integration. Our results offer insight
      into the requirements for using a chimeric zinc finger-piggyBac transposase to
      direct integration into a user-defined chromosomal location.

PMID- 21730971
TI  - Age-dependent dystrophin loss and genetic reconstitution establish a molecular
      link between dystrophin and heart performance during aging.
AB  - The aging-related decline in cardiac function is an important public health
      problem. The molecular basis of age-dependent loss of cardiac function is largely
      unknown and there are no effective therapies addressing this important form of
      heart disease. This study evaluates the role of the cytoskeletal protein
      dystrophin in the process of normal cardiac aging. Here, we show that the
      cytoskeletal protein dystrophin in the hearts of old mice is significantly
      decreased to a level of 36% that of young mice, whereas other key members of the
      dystrophin complex are unchanged. Age-dependent decreased ejection fraction was
      rescued by systemic delivery of an adeno-associated viral vector harboring a
      functional micro-dystrophin cassette (48.9 +/- 2.5% in untreated aged vs. 61.6 +/
      7.4% in treated aged mice, compared to 67.1 +/- 2.6% in young mice). These data
      provide the first direct evidence that decreased dystrophin levels are an
      important modulator of cardiac function in the aged heart.

PMID- 21730972
TI  - RNA interference improves myopathic phenotypes in mice over-expressing FSHD
      region gene 1 (FRG1).
AB  - Muscular dystrophies, and other diseases of muscle, arise from recessive and
      dominant gene mutations. Gene replacement strategies may be beneficial for the
      former, while gene silencing approaches may provide treatment for the latter. In
      the last two decades, muscle-directed gene therapies were primarily focused on
      treating recessive disorders. This disparity at least partly arose because
      feasible mechanisms to silence dominant disease genes lagged behind gene
      replacement strategies. With the discovery of RNA interference (RNAi) and its
      subsequent development as a promising new gene silencing tool, the landscape has
      changed. In this study, our objective was to demonstrate proof-of-principle for
      RNAi therapy of a dominant myopathy in vivo. We tested the potential of adeno
      associated viral (AAV)-delivered therapeutic microRNAs, targeting the human
      Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1), to correct
      myopathic features in mice expressing toxic levels of human FRG1 (FRG1(-high)
      mice). We found that FRG1 gene silencing improved muscle mass, strength, and
      histopathological abnormalities associated with muscular dystrophy in FRG1(-high)
      mice, thereby demonstrating therapeutic promise for treatment of dominantly
      inherited myopathies using RNAi. This approach potentially applies to as many as
      29 different gene mutations responsible for myopathies inherited as dominant
      disorders.

PMID- 21730973
TI  - Hepatorenal correction in murine glycogen storage disease type I with a double
      stranded adeno-associated virus vector.
AB  - Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose
      6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life
      threatening hypoglycemia and proteinuria progressing to renal failure. A double
      stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human
      G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we
      evaluated efficacy in 12-day-old G6pase (-/-) mice. Hypoglycemia during fasting
      (plasma glucose <100 mg/dl) was prevented for >6 months by the dsAAV2/7,
      dsAAV2/8, and dsAAV2/9 vectors. Prolonged fasting for 8 hours revealed
      normalization of blood glucose following dsAAV2/9 vector administration at the
      higher dose. The glycogen content of kidney was reduced by >65% with both the
      dsAAV2/7 and dsAAV2/9 vectors, and renal glycogen content was stably reduced
      between 7 and 12 months of age for the dsAAV2/9 vector-treated mice. Every vector
      treated group had significantly reduced glycogen content in the liver, in
      comparison with untreated G6pase (-/-) mice. G6Pase was expressed in many renal
      epithelial cells of with the dsAAV2/9 vector for up to 12 months. Albuminuria and
      renal fibrosis were reduced by the dsAAV2/9 vector. Hepatorenal correction in
      G6pase (-/-) mice demonstrates the potential of AAV vectors for the correction of
      inherited diseases of metabolism.

PMID- 21730974
TI  - Functional and prognostic relevance of the homeobox protein MSX2 in malignant
      melanoma.
AB  - BACKGROUND: The homeobox containing transcription factor MSX2 is a key regulator
      of embryonic development and has been implicated to have a role in breast and
      pancreatic cancer. METHODS: Using a selection of two- and three-dimensional in
      vitro assays and tissue microarrays (TMAs), the clinical and functional relevance
      of MSX2 in malignant melanoma was explored. A doxycyline-inducible over
      expression system was applied to study the relevance of MSX2 in vitro. For TMA
      construction, tumour material from 218 melanoma patients was used. RESULTS:
      Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the
      invasive capacity of melanoma cells in three-dimensional culture. MSX2 over
      expression was shown to affect several signalling pathways associated with cell
      invasion and survival. Downregulation of N-Cadherin, induction of p21 and
      inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression
      was found to correlate significantly with increased recurrence-free survival
      (P=0.008). Nuclear expression of MSX2 did not result in significant survival
      correlations, suggesting that the beneficial effect of MSX2 may be independent of
      its DNA binding activity. CONCLUSIONS: MSX2 may be an important regulator of
      melanoma cell invasion and survival. Cytoplasmic expression of the protein was
      identified as biomarker for good prognosis in malignant melanoma patients.

PMID- 21730975
TI  - Second to fourth digit ratio (2D:4D) and prostate cancer risk in the Melbourne
      Collaborative Cohort Study.
AB  - BACKGROUND: The ratio of the lengths of index and ring fingers (2D:4D) is a
      marker of prenatal exposure to sex hormones, with low 2D:4D being indicative of
      high prenatal androgen action. Recent studies have reported a strong association
      between 2D:4D and risk of prostate cancer. METHODS: A total of 6258 men
      participating in the Melbourne Collaborative Cohort Study had 2D:4D assessed. Of
      these men, we identified 686 incident prostate cancer cases. Hazard ratios (HRs)
      and confidence intervals (CIs) were estimated for a standard deviation increase
      in 2D:4D. RESULTS: No association was observed between 2D:4D and prostate cancer
      risk overall (HRs 1.00; 95% CIs, 0.92-1.08 for right, 0.93-1.08 for left). We
      observed a weak inverse association between 2D:4D and risk of prostate cancer for
      age <60, however 95% CIs included unity for all observed ages. CONCLUSION: Our
      results are not consistent with an association between 2D:4D and overall prostate
      cancer risk, but we cannot exclude a weak inverse association between 2D:4D and
      early onset prostate cancer risk.

PMID- 21730976
TI  - Differential roles of STAT3 depending on the mechanism of STAT3 activation in
      gastric cancer cells.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is a
      transcription factor that is activated in response to growth factors and
      cytokines, and which contributes to the regulation of cell proliferation,
      apoptosis, and motility in many human tumour types. METHODS: We investigated the
      mechanisms of STAT3 activation and the function of STAT3 depending on its
      mechanism of activation in gastric cancer cells. RESULTS: The MET-tyrosine kinase
      inhibitor (TKI) and cell transfection with a small interfering RNA (siRNA)
      specific for MET mRNA inhibited STAT3 phosphorylation in MET-activated cells,
      indicating that STAT3 activation is linked to MET signalling. Forced expression
      of a constitutively active form of STAT3 also attenuated MET-TKI-induced
      apoptosis, suggesting that inhibition of STAT3 activity contributes to MET-TKI
      induced apoptosis. MKN1 and MKN7 cells, both of which are negative for MET
      activation, produced interleukin-6 (IL-6) that activated STAT3 through the Janus
      kinase pathway. Depletion of STAT3 by siRNA inhibited migration and invasion of
      these cells, suggesting that STAT3 activated by IL-6 contributes to regulation of
      cell motility. CONCLUSION: Our data thus show that activated STAT3 contributes to
      either cell survival or motility in gastric cancer cells, and that these actions
      are related to different mechanisms of STAT3 activation.

PMID- 21730977
TI  - Self-sampling and HPV testing or ordinary Pap-smear in women not regularly
      attending screening: a randomised study.
AB  - BACKGROUND: Most women with cervical cancer have not participated in Pap-smear
      screening. Self-sampling of vaginal fluid in combination with high-risk HPV
      testing may be a method to increase the attendance rate. METHODS: A total of 4060
      women, 39-60 years old, who had not attended the organised Pap-smear screening
      for 6 years or more were randomised into two equal groups. A study group was
      offered to self-sample vaginal fluid (Qvintip) at home and/or recommended to
      attend the Pap-smear screening. The collected fluid after self-sampling was
      examined for the presence of high-risk HPV (Hybrid Capture 2 method). Controls
      were only recommended to attend the Pap-smear screening. The end point was a
      histological identification of CIN2-3. RESULTS: The participation rate was 39%
      (771 out of 2000) in the self-sampling group and 9% (188 out of 2060) in the
      conventional cytology (P<0.001). The number of histological CIN2-3 alterations
      detected was 0.4% (8 out of 2000) among women offered self-sampling of vaginal
      fluid and 0.07% (3 out of 4060) in women offered Pap-smears. The odds ratio (OR)
      for offering self-sampling and HPV testing instead of Pap-smear screening for
      detection of CIN2-3 was OR=5.42 (95% CI: 1.30-31.8). CONCLUSION: Offering self
      sampling of vaginal fluid followed by a high-risk HPV test was considerably more
      effective for detection of histological CIN2-3 lesions in comparison with
      offering Pap-test in a midwife reception in women not regularly attending
      organised screening.

PMID- 21730978
TI  - KRAS mutations detected by the amplification refractory mutation system-Scorpion
      assays strongly correlate with therapeutic effect of cetuximab.
AB  - BACKGROUND: We aimed to compare the sensitive and quality-controlled KRAS testing
      with direct sequencing and to assess the impact on decision making of treatment.
      PATIENTS AND METHODS: We analysed genomic DNA isolated from macrodissected
      formalin-fixed paraffin-embedded specimens by direct sequencing and an
      amplification refractory mutation system-Scorpion assay (ARMS/S) method.
      Cetuximab was administered to patients identified as having wild-type (WT) KRAS
      using direct sequencing. Therapeutic effects were evaluated according to their
      KRAS status as determined by ARMS/S. RESULTS: Among the 159 patients, the overall
      mutation rate was determined to be 37.0% by direct sequencing and 44.0% by
      ARMS/S. For the patients diagnosed as WT by direct sequencing and treated with
      cetuximab (n=47), a response rate of 16.0% was observed for 38 ARMS/S WT
      patients, whereas 9 ARMS/S mutant (MUT) patients failed to respond. The ARMS/S WT
      patients showed significant improvement in progression-free survival (PFS) and
      overall survival (OS) compared with ARMS/S MUT patients (PFS median 5.0 vs 1.7
      months, hazards ratio (HR)=0.29, P=0.001; OS median 12.1 vs 3.8 months, HR=0.26,
      P=0.001). CONCLUSION: Sensitive and quality-controlled KRAS testing may provide
      improved predictive power to determine the efficacy of anti-epidermal growth
      factor antibodies.

PMID- 21730979
TI  - Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast
      and ovarian cancer cell lines.
AB  - BACKGROUND: The ataxia telangiectasia mutated and Rad3-related kinase (ATR) has a
      key role in the signalling of stalled replication forks and DNA damage to cell
      cycle checkpoints and DNA repair. It has long been recognised as an important
      target for cancer therapy but inhibitors have proved elusive. As NU6027,
      originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2
      independent manner we postulated that it may inhibit ATR. METHODS: Cellular ATR
      kinase activity was determined by CHK1 phosphorylation in human fibroblasts with
      inducible dominant-negative ATR-kinase dead expression and human breast cancer
      MCF7 cells. Cell cycle effects and chemo- and radiopotentiation by NU6027 were
      determined in MCF7 cells and the role of mismatch repair and p53 was determined
      in isogenically matched ovarian cancer A2780 cells. RESULTS: NU6027 is a potent
      inhibitor of cellular ATR activity (IC(50)=6.7 MUM) and enhanced hydroxyurea and
      cisplatin cytotoxicity in an ATR-dependent manner. NU6027 attenuated G2/M arrest
      following DNA damage, inhibited RAD51 focus formation and increased the
      cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy
      but not the antimitotic, paclitaxel. In A2780 cells sensitisation to cisplatin
      was greatest in cells with functional p53 and mismatch repair (MMR) and
      sensitisation to temozolomide was greatest in p53 mutant cells with functional
      MMR. Importantly, NU6027 was synthetically lethal when DNA single-strand break
      repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition
      or defects in XRCC1. CONCLUSION: NU6027 inhibits ATR, impairing G2/M arrest and
      homologous recombination thus increasing sensitivity to DNA-damaging agents and
      PARP inhibitors. It provides proof of concept data for clinical development of
      ATR inhibitors.

PMID- 21730980
TI  - Reduced association of anti-apoptotic protein Mcl-1 with E3 ligase Mule increases
      the stability of Mcl-1 in breast cancer cells.
AB  - BACKGROUND: Mechanisms that increase resistance to apoptosis help promote
      cellular transformation. Cancer cells have deregulated apoptotic pathways, where
      increased expression and stability of anti-apoptotic proteins Mcl-1 and Bcl-2
      increases resistance to apoptosis. Pathways that increase the stability of
      proteins in cancer cells remain poorly understood. METHODS: Using human mammary
      epithelial and established breast cancer cell lines, we assessed the mechanisms
      that increase the stability of anti-apoptotic proteins in breast cancer cells by
      caspase assay, western blot, small-inhibitory RNA treatment and
      immunoprecipitation. RESULTS: While breast cancer cells were resistant to de novo
      inhibition of protein synthesis, a rapid proteosome-mediated degradation of Mcl-1
      and Bcl-2 induced apoptosis in mammary epithelial cells. Although Mule, an E3
      ligase that targets Mcl-1 for degradation was expressed in mammary epithelial and
      breast cancer cell lines, rapid increase of polyubiquitinated Mcl-1 and Bcl-2 was
      detected only in mammary epithelial cells. Only transient formation of the Mule
      Mcl-1 complex was detected in breast cancer cells. Downregulation of pERK1/2 in
      breast cancer cells reduced Mcl-1 levels and increased Mcl-1/Mule complex.
      CONCLUSION: Our findings suggest that reduced Mule/Mcl-1 complex has a
      significant role in increasing the stability of Mcl-1 in breast cancer cells and
      increased resistance to apoptosis.

PMID- 21730981
TI  - High FOXP3+ regulatory T-cell density in the sentinel lymph node is associated
      with downstream non-sentinel lymph-node metastasis in gastric cancer.
AB  - BACKGROUND: We aimed to evaluate the immunologic nature of sentinel lymph nodes
      (SLNs) in gastric cancer patients and to determine whether it can predict non-SLN
      metastasis. METHODS: Sentinel lymph node samples were collected from 64 gastric
      carcinoma patients who had undergone gastrectomy with SLN biopsy. One
      representative SLN sample was selected from each patient and was subjected to
      immunostaining for CD8, CD57, FOXP3, and DC-LAMP. The numbers of marker-positive
      cells in each sample were counted. The relationships between various immune cell
      densities and clinicopathologic parameters or metastasis status of SLNs and non
      SLNs were sought. RESULTS: High FOXP3+ Treg density of the SLN was found to be
      significantly associated with the presence of metastasis in either SLNs or non
      SLNs. DC-LAMP+ cell density of the SLN was the highest at the isolated tumours
      cell level, and this decreased along with an increase in tumour metastasis in
      either SLNs or non-SLNs. Univariate and multivariate logistic regression models
      revealed that high FOXP3+ Treg density of the SLN was an independently
      significant predictor of non-SLN metastasis. CONCLUSIONS: This study is the first
      to indicate an important role of SLNs in metastatic dissemination of gastric
      cancer. Our findings suggest that Tregs could be a new therapeutic target for
      regulating the metastasis of gastric cancer.

PMID- 21730982
TI  - EGFR gene amplification is related to adverse clinical outcomes in cervical
      squamous cell carcinoma, making the EGFR pathway a novel therapeutic target.
AB  - BACKGROUND: The aim of this study was to investigate the patterns of epidermal
      growth factor receptor (EGFR) overexpression, EGFR gene amplification, and the
      presence of activating mutations in the tyrosine kinase domain of this gene in
      squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas of the
      uterine cervix. METHODS: The EGFR expression, amplification, and mutation in
      cervical carcinomas were assessed by immunohistochemistry, fluorescence in situ
      hybridisation, and PCR-SSCP, respectively, and correlated with clinical data
      collected by a retrospective chart review. A functional assessment was performed
      by inactivating EGFR in cervical cancer cells with the potent inhibitor AG1478.
      RESULTS: Immunohistochemical analysis revealed that 6 out of 59 (10.2%) cervical
      squamous cell carcinomas showed significant amplification of the EGFR locus,
      whereas none of the 52 adeno/adenosquamous cell carcinomas had detectable EGFR
      amplification (P<0.05). The EGFR amplification significantly correlated with
      shorter overall survival (P=0.001) in cervical squamous cell carcinomas.
      Multivariate analysis showed that EGFR gene amplification was an independent
      prognostic factor for overall survival (P=0.011). None of the squamous cell
      carcinomas (0%: 0 out of 32) had detectable oncogenic mutations in EGFR exons 18
      through 21. The frequencies of KRAS and BRAF mutations were very low in both
      squamous and adeno/adenosquamous cell carcinomas. Sensitivity of cervical cancer
      cells to AG1478 depended on the presence of EGFR overexpression. AG1478-induced
      EGFR inactivation in cell lines with EGFR overexpression significantly suppressed
      tumour development and progression in a mouse xenograft model. CONCLUSION: Our
      data suggest that EGFR signalling is important in a subset of cervical squamous
      cell carcinomas and that anti-EGFR therapy may benefit patients who carry the
      7p11.2 amplicon in their tumours.

PMID- 21730983
TI  - Strengthening health systems for equity and social justice in South Africa: the
      24th anniversary of the Centre for Health Policy.

PMID- 21730984
TI  - Research in support of health systems transformation in South Africa: the
      experience of the Centre for Health Policy.
AB  - We describe the role and experience of the Centre for Health Policy (CHP), a
      university-based research unit established in 1987, in influencing and supporting
      health systems transformation in South Africa over two decades. During 2010, we
      analyzed relevant documents and conducted interviews with 25 key informants.
      CHP's research has contributed directly to health policy development and
      implementation while also changing the way government understood or approached
      policy issues. Key success factors for policy influence are: research quality and
      trustworthiness, strategic alliances and networking, and capacity building. CHP's
      challenges include identifying new funding sources and sustaining a high public
      profile. The lessons for other countries are to: conduct good quality, relevant
      research based on strong ethical values; build and maintain open and honest
      relationships with government; recognize and adapt to changes in the policy
      environment; develop capacity as part of a continuous programme; and seek core
      funding that ensures research independence and public accountability.

PMID- 21730985
TI  - Inequities in access to health care in South Africa.
AB  - Achieving equitable universal health coverage requires the provision of
      accessible, necessary services for the entire population without imposing an
      unaffordable burden on individuals or households. In South Africa, little is
      known about access barriers to health care for the general population. We explore
      affordability, availability, and acceptability of services through a nationally
      representative household survey (n = 4668), covering utilization, health status,
      reasons for delaying care, perceptions and experiences of services, and health
      care expenditure. Socio-economic status, race, insurance status, and urban-rural
      location were associated with access to care, with black Africans, poor,
      uninsured and rural respondents, experiencing greatest barriers. Understanding
      access barriers from the user perspective is important for expanding health-care
      coverage, both in South Africa and in other low- and middle-income countries.

PMID- 21730986
TI  - Utilization of traditional healers in South Africa and costs to patients:
      findings from a national household survey.
AB  - The use of traditional medicine is widespread in developing countries. We report
      on the utilization of traditional healers, using data obtained in a 2008 national
      survey of 4762 households in South Africa. Only 1.2 per cent of survey
      participants reported utilization of traditional healers. Respondents' reasons
      for visiting traditional healers included continuity of care and a belief in
      their effectiveness. Traditional healer utilization rates (0.02 visits per month)
      were considerably lower compared to utilization rates of public sector clinics
      (0.18 visits per month) or hospitals (0.09 visits per month). Almost three
      quarters of the poorest quintile spent more than 10 per cent of their household
      expenditure in the previous month on traditional healers. Given the use of two
      parallel health-care systems, policy-makers should develop strategies to protect
      poor South Africans from out-of-pocket payments for health care. Simultaneous
      utilization of these systems evidently absorbs expenditure from low-income
      households significantly.

PMID- 21730987
TI  - You become afraid to tell them that you are gay: health service utilization by
      men who have sex with men in South African cities.
AB  - We describe the utilization of health services by men who have sex with men (MSM)
      in South African cities, their perceptions of available health services, and
      their service preferences. We triangulated data from 32 key informant interviews
      (KIIs), 18 focus group discussions (FGDs) with MSM in four cities, and a survey
      of 285 MSM in two cities, recruited through respondent-driven sampling in 2008.
      FGDs and KIIs revealed that targeted public health sector programs for MSM were
      limited, and that MSM experienced stigma, discrimination, and negative health
      worker attitudes. Fifty-seven per cent of the survey participants had used public
      health services in the previous 12 months, and 69 per cent had no private health
      insurance, with no difference by HIV status. Despite these findings, South Africa
      is well placed to take the lead in sub-Saharan Africa in providing responsive and
      appropriate HIV services for MSM.

PMID- 21730988
TI  - Exploring perceptions of HIV risk and health service access among Zimbabwean
      migrant women in Johannesburg: a gap in health policy in South Africa?
AB  - We present qualitative data from a 2005 exploratory study, recently published
      studies, and an analysis of the Department of Health's strategic plan to
      highlight the need for a broader policy debate on health-care access for migrants
      in South Africa. We conducted in-depth interviews with 15 Zimbabwean women living
      in inner-city Johannesburg to document the special characteristics of this group
      of migrants, enquiring about their perceptions of HIV risk, and experiences of
      health services in South Africa. We identified access barriers, namely
      perceptions of relatively low HIV risk, severely constrained financial
      circumstances, uncertain legal status, and experiences of unresponsive health
      workers. We recommend that migrant-health rights be placed on South Africa's
      policy agenda, migrants be included in HIV prevention programs and that health
      workers be sensitized to the needs of migrants.

PMID- 21730989
TI  - Social solidarity and civil servants' willingness for financial cross
      subsidization in South Africa: implications for health financing reform.
AB  - In South Africa, anticipated health sector reforms aim to achieve universal
      health coverage for all citizens. Success will depend on social solidarity and
      willingness to pay for health care according to means, while benefitting on the
      basis of their need. In this study, we interviewed 1330 health and education
      sector civil servants in four South African provinces, about potential income
      cross-subsidies and financing mechanisms for a National Health Insurance. One
      third was willing to cross-subsidize others and half favored a progressive
      financing system, with senior managers, black Africans, or those with tertiary
      education more likely to choose these options than lower-skilled staff, white,
      Indian or Asian respondents, or those with primary or less education. Insurance-
      and health-status were not associated with willingness to pay or preferred type
      of financing system. Understanding social relationships, identities, and shared
      meanings is important for any reform striving toward universal coverage.

PMID- 21730990
TI  - Reflections on health-care reforms in South Africa.
AB  - We describe an economic framework, including demand- and supply-side factors, for
      approaching the analysis and planning of health system reform in South Africa, in
      order to avoid piecemeal debates. We argue that there is an urgent need to re
      engineer the way health facilities are internally organized to achieve better
      productivity and responsiveness. We argue that funding is not the central problem
      of the South African public health system but rather the enormous inefficiencies
      in management and low productivity; and that separating the purchase from the
      supply side is a critical component of making significant efficiency gains.
      Finally, we suggest that income inequalities and a divided health system in South
      Africa are departure points for reform initiatives. We must build on the
      strengths of the South African health system as we plan for the eventual
      achievement of a more homogeneous health-care system across the public and
      private sectors.

PMID- 21730991
TI  - Population health in South Africa: dynamics over the past two decades.
AB  - South Africa has experienced a rapid and complex health transition over the past
      two decades. Mortality has worsened in virtually all age groups, driven largely
      by HIV and AIDS. The morbidity profile comprises coexisting infectious and non
      communicable diseases--including new infections such as HIV and AIDS, and
      emerging conditions such as vascular illness and diabetes--together with
      persisting child diarrhea and malnutrition, and high levels of interpersonal
      violence and accidents. Risk factors for cardiovascular disease are high even in
      rural parts of the country, with high levels of obesity rendering women at
      greater risk for metabolic disease. Reducing the negative impacts of the health
      transition will require targeted efforts within the health and social sectors, as
      well as broader development initiatives. Government should provide strong
      leadership, and priorities for action must be underpinned by a robust evidence
      base.

PMID- 21730992
TI  - Environment and health in South Africa: gains, losses, and opportunities.
AB  - South Africans face a range of preventable environmental hazards to their health,
      many of which are rooted in the country's colonial and apartheid past, and
      ongoing poverty and inequality. Since the advent of democracy in the country,
      government has made considerable progress in improving living conditions and in
      developing the legal framework to prevent and manage environmental contamination.
      Considerable, under-exploited potential also exists in South Africa to prevent
      disease, including infectious and chronic diseases, and to promote health through
      a more holistic and public health approach. This article summarizes the main
      environmental health concerns and reflects on mechanisms and opportunities to
      improve public environmental health.

PMID- 21730993
TI  - Linking public health training and health systems development in sub-Saharan
      Africa: opportunities for improvement and collaboration.
AB  - In sub-Saharan Africa previous health gains have been reversed and many countries
      are not on track to achieving the Millennium Development Goals. The reasons are
      multifaceted but relate fundamentally to poorly functioning health systems and
      the HIV, AIDS, and tuberculosis epidemics. Although population health can be
      improved through specific health interventions that target high burden diseases,
      these interventions must be offered within a functional health system for optimal
      effectiveness. Schools of Public Health in Africa should respond to the many
      systemic issues that confound improvements in population level health through
      reviewing approaches to health professional training that incorporates a public
      health approach, focusing on health systems research; collaboration, advocacy and
      networking; and strengthening health systems management. Institutional mechanisms
      to define joint research agendas and two-way exchanges between universities and
      national health systems are required.

PMID- 21730994
TI  - Exploring antiretroviral treatment adherence in an urban setting in South Africa.
AB  - Antiretroviral treatment requires high levels of adherence to be effective. This
      qualitative study explores the reasons for poor adherence among 22 purposively
      selected poor urban participants in South Africa. Over a 4-month period in 2009,
      we prospectively investigated experiences of HIV diagnosis and treatment,
      adherence, and withdrawal from treatment. Patients with no stable food sources
      faced significant barriers in adhering to treatment regimens and staying
      sufficiently healthy to search for, obtain or retain a job. The narratives also
      identify the influence on adherence of self-esteem and social support,
      vulnerability generated by ill health, gendered conflict, social inequities
      amplified by HIV, and exhaustion due to the social burden of the epidemic. Multi
      dimensional, inter-sectoral programs that tackle the social determinants of
      health, such as food insecurity, poverty, gendered inequities, and treatment
      adherence are more likely to be successful, than single interventions to support
      adherence.

PMID- 21730995
TI  - Occupational lung disease in the South African mining industry: research and
      policy implementation.
AB  - South African miners face an epidemic of occupational lung diseases. Despite a
      plethora of research on the mining industry, and the gold mining industry in
      particular, research impact (including disease surveillance) on policy
      implementation and occupational health systems performance lags. We describe the
      gold mining environment, and research on silicosis, tuberculosis, HIV and AIDS,
      and compensation for occupational disease including initiatives to influence
      policy and thus reduce dust levels and disease. As these have been largely
      unsuccessful, we identify possible impediments, some common to other low- and
      middle-income countries, to the translation of research findings and policy
      initiatives into effective interventions.

PMID- 21730996
TI  - Analyzing the implementation of the rural allowance in hospitals in North West
      Province, South Africa.
AB  - Using a policy analysis framework, we analyzed the implementation and perceived
      effectiveness of a rural allowance policy and its influence on the motivation and
      retention of health professionals in rural hospitals in the North West province
      of South Africa. We conducted 40 in-depth interviews with policy-makers, hospital
      managers, nurses, and doctors at five rural hospitals and found weaknesses in
      policy design and implementation. These weaknesses included: lack of evidence to
      guide policy formulation; restricting eligibility for the allowance to doctors
      and professional nurses; lack of clarity on the definition of rural areas; weak
      communication; and the absence of a monitoring and evaluation framework. Although
      the rural allowance was partially effective in the recruitment of health
      professionals, it has had unintended negative consequences of perceived
      divisiveness and staff dissatisfaction. Government should take more account of
      contextual and process factors in policy formulation and implementation so that
      policies have the intended impact.

PMID- 21730997
TI  - Exploring task-shifting practices in antiretroviral treatment facilities in the
      Free State Province, South Africa.
AB  - There is good progress with the implementation of South Africa's antiretroviral
      treatment program. The country, however, faces human resource shortages that
      could be addressed through appropriate task shifting. During 2009, we studied
      task shifting from nurses to community health workers (CHWs) for HIV treatment
      and care at 12 primary health-care clinics in Free State Province, South Africa.
      We found inefficiency in nurse deployment, and nurses spent considerable time on
      training, counseling, and administrative tasks that could be shifted to CHWs.
      Such a shift will require the South African Ministry of Health to recognize CHWs
      formally in the health system.

PMID- 21731000
TI  - Rationale and methods of the European Food Consumption Validation (EFCOVAL)
      Project.
AB  - BACKGROUND/OBJECTIVES: The overall objective of the European Food Consumption
      Validation (EFCOVAL) Project was to further develop and validate a trans-European
      food consumption method to be used for the evaluation of the intake of foods,
      nutrients and potentially hazardous chemicals within the European population.
      SUBJECTS/METHODS: The EFCOVAL Project was carried out by 13 institutes from 11
      European countries. The main activities were centered on the three main
      objectives of the project organized in different sub-projects. RESULTS: In
      EFCOVAL, EPIC-Soft (the software developed to conduct 24-h dietary recalls (24
      HDRs) in the European Prospective Investigation into Cancer and Nutrition (EPIC)
      Study) was reprogrammed and adapted according to prioritized specifications,
      resulting in a software program working under the Windows operating system. In
      parallel of the EPIC-Soft development, the repeated 24-HDR method using EPIC-Soft
      and a food propensity questionnaire was evaluated against biomarkers in 24-h
      urine collections and in blood samples among adults from Belgium, the Czech
      Republic, (the South of) France, the Netherlands and Norway. As a result from an
      expert workshop on a proposed dietary assessment method for children (4-12
      years), the suggested method was tested in a feasibility study in Denmark and
      Spain among children of 4-5, 7-8 and 12-13 years. To ensure that collected data
      had sufficient detail in food description for the assessment of additives and
      contaminants to foods the EPIC-Soft databases were adapted. Finally, the EFCOVAL
      Consortium developed a statistical tool (Multiple Source Method) for estimating
      the usual intake and distribution, which has been tested using real food
      consumption data and compared with three other statistical methods through a
      simulation study. In addition, a methodology was developed to quantify
      uncertainty due to portion-size estimation in usual intake distributions.
      CONCLUSION: The findings of EFCOVAL provide sufficient evidence to conclude that
      the repeated 24-HDR using EPIC-Soft for standardization in combination with a
      food propensity questionnaire and modeling of usual intake is a suitable method
      for pan-European surveillance of nutritional adequacy and food safety among
      healthy adults and maybe in children aged 7 years and older.

PMID- 21731001
TI  - The European Food Consumption Validation Project: conclusions and
      recommendations.
AB  - BACKGROUND/OBJECTIVES: To outline and discuss the main results and conclusions of
      the European Food Consumption Validation (EFCOVAL) Project. SUBJECTS/METHODS: The
      EFCOVAL Project was carried out within the EU Sixth Framework Program by
      researchers in 11 EU countries. The activities focused on (1) the further
      development of the EPIC-Soft software (the software developed to conduct 24-h
      dietary recalls (24-HDRs) in the European Prospective Investigation into Cancer
      and Nutrition (EPIC) Study) and the validation of the 2-day non-consecutive 24
      HDR method using EPIC-Soft, (2) defining and investigating the applicability of
      the most appropriate dietary assessment method to younger age groups and
      expanding the applicability of the software for use in exposure assessment of
      some potentially hazardous chemicals and (3) to improve the methodology and
      statistical methods that estimate usual intake distributions from short-term
      dietary intake information and develop a methodology to quantify uncertainty in
      usual intake distributions. RESULTS: The preexisting EPIC-Soft application was
      reprogrammed into a Windows environment and more than 60 new specifications were
      implemented in the software. A validation study showed that two non-consecutive
      EPIC-Soft 24-HDRs are suitable to estimate the usual intake distributions of
      protein and potassium of European adult populations. The 2-day non-consecutive 24
      HDRs in combination with a food propensity questionnaire also appeared to be
      appropriate to rank individuals according to their fish and fruit and vegetable
      intake in a comparable way in five European centers. Dietary intake of (young)
      children can be assessed by the combination of EPIC-Soft 24-HDRs and food
      recording booklets. The EPIC-Soft-standardized method of describing foods is
      useful to estimate dietary exposure to potentially hazardous chemicals such as
      specific flavoring substances. With the developed Multiple Source Method,
      repeated non-consecutive 24-HDR data in combination with food propensity data can
      be used to estimate the population distribution of the usual intake by estimating
      the individual usual intakes. CONCLUSIONS: The findings provide sufficient
      evidence to conclude that the repeated 24-HDR using EPIC-Soft for standardization
      in combination with a food propensity questionnaire and modeling of usual intake
      is a suitable method for pan-European surveillance of nutritional adequacy and
      food safety among healthy adults and maybe in children aged 7 years and older. To
      facilitate this methodology in other European countries, the next step is to
      provide and standardize an implementation plan that accounts for maintenance and
      updates, sampling designs, national surveillance programs, tailored capacity
      building and training, and linkage to food composition and occurrence databases.

PMID- 21731002
TI  - Inventory of experiences from national/regional dietary monitoring surveys using
      EPIC-Soft.
AB  - BACKGROUND/OBJECTIVES: The EPIC-Soft 24-h recall (the software developed to
      conduct 24-h dietary recalls (24-HDRs) in the European Prospective Investigation
      into Cancer and Nutrition (EPIC) Study) has been used in several
      regional/national dietary monitoring surveys. The main objective of the study was
      to present and discuss design, settings, logistics, data management and quality
      controls of dietary monitoring surveys that used EPIC-Soft for the collection of
      food consumption data. SUBJECTS/METHODS: Within European Food Consumption
      Validation (EFCOVAL), a questionnaire including questions on current/past EPIC
      Soft experiences and requirements for the future was developed and sent to all
      institutes that used EPIC-Soft in their food consumption survey(s) (five surveys
      in four different countries). RESULTS: EPIC-Soft was used in the national food
      consumption survey in Belgium (>= 15-97 years), Germany (14-80 years), the
      Netherlands (19-30 years and 2-6 years) and Spain (regional only; 4-18 years).
      Participation rates in these surveys were 46% (Belgium), 42% (Germany), 42%
      (Dutch survey in adults), 79% (Dutch survey in children) and 77% (Basque survey).
      Two 24-HDRs were collected by conducting face-to-face interviews in Belgium and
      Spain, and through telephone interviews in Germany and the Netherlands. Except
      the Netherlands (19-30 years), where the study was conducted only in autumn, in
      all other countries the study was conducted throughout the four seasons,
      including all days of the week. Interviews were conducted by dietitians, except
      in Germany and Spain. Mean EPIC-Soft interview time was 20-34 min. The dropout
      rate between the first and second interviews was low (<7.5%) in all surveys.
      CONCLUSION: EPIC-Soft has been used in different study settings and populations
      for nutritional exposure assessments. To guarantee the comparability of data
      across countries, recommendations for the design of future pan-European dietary
      monitoring surveys using EPIC-Soft should be drawn.

PMID- 21731003
TI  - Respondents' evaluation of the 24-h dietary recall method (EPIC-Soft) in the
      EFCOVAL Project.
AB  - BACKGROUND: To improve participation rate, accuracy and respondents' compliance,
      it is important to know the respondents' viewpoint. OBJECTIVE: To evaluate
      respondents' preferences and perception about the EPIC-Soft (the software
      developed to conduct 24-h dietary recalls (24-HDRs) in the European Prospective
      Investigation into Cancer and Nutrition (EPIC) Study) 24-HDR interviews and to
      compare these preferences and perception between population groups (for example,
      between genders). DESIGN: Data were collected in Belgium, Czech Republic, France,
      the Netherlands and Norway in 2007. Two 24-HDRs (face-to-face and telephone
      administered) were conducted using EPIC-Soft. An evaluation questionnaire on
      different study aspects was completed by the respondents. SETTING: Data were
      collected in the European Food Consumption Validation Study. SUBJECTS: A
      convenience sample of 600 apparently healthy men and women, 45-65 years old and
      including all educational levels, were recruited (120 subjects per country).
      Differences among population groups were compared by means of the chi (2)-test.
      RESULTS: A total of 585 respondents completed the evaluation questionnaire. In
      all, 88% experienced problems only to a low degree when answering face-to-face
      and telephone-administered 24-HDR using EPIC-Soft. A total of 15% would have
      preferred help of another person during the face-to-face interview in the study
      center (mainly men: P < 0.001). Significantly, more subjects in the Netherlands
      and in Norway preferred two telephone (instead of face-to-face) interviews
      compared with the other countries (P<0.001). CONCLUSION: Most subjects only
      experienced problems to a low degree during the EPIC-Soft interviews. Differences
      in preferences and capabilities to answer the EPIC-Soft interviews were
      identified between population groups (for example, gender differences).
      Therefore, the methods and the design to be used in a survey should be adapted
      according to the study population, so as to optimize response rate and
      compliance.

PMID- 21731004
TI  - Biomarker-based evaluation of two 24-h recalls for comparing usual fish, fruit
      and vegetable intakes across European centers in the EFCOVAL Study.
AB  - BACKGROUND/OBJECTIVES: A standardized methodology is important to enable
      consistent monitoring of dietary intake across European countries. For this
      reason, we evaluated the comparability of the assessment of usual food intake
      collected with two non-consecutive computerized 24-h dietary recalls (24-HDRs)
      and a food propensity questionnaire (FPQ) among five European centers.
      SUBJECTS/METHODS: Two 24-HDRs using EPIC-Soft (the software developed to conduct
      24-HDRs in the European Prospective Investigation into Cancer and Nutrition
      (EPIC) Study) were performed to determine fish, fruit and vegetable (FV) consumed
      by 600 adults in Belgium (BE), the Czech Republic (CZ), France (FR), the
      Netherlands (NL) and Norway (NO) in a validation study. An FPQ was used to
      identify non-consumers. Information from the 24-HDRs and FPQ were used to
      estimate individual usual food intake by the Multiple Source Method (MSM). Blood
      samples were drawn to determine fatty acids in phospholipids and serum
      carotenoids as biomarkers of fish, and FV intake, respectively. RESULTS: The
      pooled correlation between usual fish intake and eicosapentaenoic acid plus
      docosahexaenoic acid in phospholipids was 0.19 in men and 0.31 in women (P for
      heterogeneity >0.50) and center-specific correlations ranged between 0.08 (CZ)
      and 0.28 (BE and NO) in men, and between 0.19 (BE) and 0.55 (FR) in women. For
      usual FV intake, the pooled correlation with serum carotenoids was 0.31 in men
      and 0.40 in women (P for heterogeneity >0.10); the center-specific correlations
      varied between 0.07 (NO) and 0.52 (FR) in men, and between 0.25 (NL) and 0.45
      (NO) in women. CONCLUSION: Two standardized 24-HDRs using EPIC-Soft and an FPQ
      appeared to be appropriate to rank individuals according to their fish and FV
      intake in a comparable way among five European centers.

PMID- 21731005
TI  - Potential and requirements for a standardized pan-European food consumption
      survey using the EPIC-Soft software.
AB  - BACKGROUND/OBJECTIVES: To describe the strengths, limitations and requirements of
      using EPIC-Soft software (the software developed to conduct 24-h dietary recalls
      in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study)
      in pan-European food consumption surveys, and to discuss potentials and barriers
      for a harmonized pan-European food consumption survey. SUBJECTS/METHODS: The
      paper is based on the experiences in the 'European Food Consumption and
      Validation' Project, which included updating six existing and preparing one new
      country-specific EPIC-Soft version, applying EPIC-Soft in validation and
      feasibility studies, and estimating the intake of nutrients and flavoring
      substances. The experiences were discussed in the September 2009 workshop 'Pan
      European Food Consumption Surveys--for Standardized and Comparable Transnational
      Data Collection'. RESULTS: EPIC-Soft is suitable for detailed and standardized
      food consumption data collection in pan-European food consumption surveys. A
      thorough preparation of all aspects of the food consumption survey is important
      for the quality and efficiency during data collection and processing. The
      preparation and data-handling phase of working with EPIC-Soft is labor intensive
      and requires trained, motivated and qualified personnel. CONCLUSIONS: Given the
      suitability of EPIC-Soft as standardized dietary assessment tool in European
      dietary monitoring, the proposed strategy toward a pan-European food consumption
      survey is to prepare well, to allow flexibility in national extensions and to
      start with a limited number of countries that are interested.

PMID- 21731006
TI  - The standardized computerized 24-h dietary recall method EPIC-Soft adapted for
      pan-European dietary monitoring.
AB  - BACKGROUND/OBJECTIVES: The EPIC-Soft program (the software initially developed to
      conduct 24-h dietary recalls (24-HDRs) in the European Prospective Investigation
      into Cancer and Nutrition (EPIC) Study) was recommended as the best way to
      standardize 24-HDRs for future pan-European dietary monitoring. Within European
      Food Consumption Validation (EFCOVAL), EPIC-Soft was adapted and further
      developed on various aspects that were required to optimize its use. In this
      paper, we present the structure and main interview steps of the EPIC-Soft
      program, after implementation of a series of new specifications deemed to satisfy
      specific requirements of pan-European monitoring surveys and other international
      studies. SUBJECTS/METHODS: Updates to optimize the EPIC-Soft program were
      ascertained according to the following stepwise approach: (1) identification of
      requested specifications to be potentially implemented through an ad hoc 'EPIC
      Soft specifications questionnaire' sent to past, current and possible future
      users of the software; (2) evaluation of the specifications in collaboration with
      two ad hoc task force groups and through a workshop; (3) development of a
      technical solution for each retained specification; (4) implementation of the
      specifications by software developers; (5) testing and amendment of bugs.
      RESULTS: A number of new specifications and facilities were implemented to EPIC
      Soft program. In addition, the software underwent a full reprogramming and
      migration to a modern Windows environment, including changes in its internal
      architecture and user interface. Although the overall concept and structure of
      the initial software were not changed substantially, these improvements ease the
      current and future use of EPIC-Soft and increase further its adaptation to other
      countries and study contexts. CONCLUSIONS: EPIC-Soft is enriched with further
      functions and facilities expected to fulfil specific needs of pan-European
      dietary monitoring and risk assessment purposes. The validity, feasibility and
      relevance of this software for different national and international study
      designs, and the logistical aspects related to its implementation are reported
      elsewhere.

PMID- 21731007
TI  - Recommendations for a trans-European dietary assessment method in children
      between 4 and 14 years.
AB  - BACKGROUND/OBJECTIVES: The main objective of European Food Consumption Validation
      (EFCOVAL)-child Project is to define and evaluate a trans-European methodology
      for undertaking national representative dietary surveys among children in the age
      group of 4-14 years. In the process of identifying the best dietary assessment
      methodologies, experts were brought together at a workshop. The paper presents
      the discussion of the best available method and the final recommendations for a
      trans-European dietary assessment method among 4- to 14-year-old children.
      SUBJECTS/METHODS: The starting point was to investigate whether the method (two
      non-consecutive 24-h dietary recalls (24-HDRs)) suggested for the adults in
      European Food Consumption Survey Method (EFCOSUM) would be usable for children in
      the age group between 4 and 14 years. However, all available dietary assessment
      methods were included in the discussion to ensure that the final recommendation
      would be based on the best evidence. Six criteria were defined and used as
      additional guidance in the process. RESULTS: The literature does not give a clear
      recommendation on the dietary assessment methods that are most suitable for
      children in the age group of 4-14 years. Nevertheless, on the basis of the
      literature, the recommendations were separated for preschoolers (4-6 years) and
      schoolchildren (7-14 years). CONCLUSION: For preschoolers, two non-consecutive
      days of a structured food record are recommended, using a (for children adapted)
      picture booklet and household measures for portion-size estimation. For
      schoolchildren, repeated 24-HDRs are recommended, using a picture booklet and
      household measures for portion-size estimation. In addition, the child should
      bring a booklet to register what is eaten out of home. One parent should assist
      the schoolchild at the 24-HDR interview, and therefore face-to-face interviews
      are required.

PMID- 21731008
TI  - Feasibility of 2 * 24-h dietary recalls combined with a food-recording booklet,
      using EPIC-Soft, among schoolchildren.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the feasibility of
      the suggested trans-European methodology for undertaking representative dietary
      surveys among schoolchildren: 2 * 24-h dietary recalls (24-HDRs) combined with a
      food-recording booklet, using EPIC-Soft (the software developed to conduct 24
      HDRs in the European Prospective Investigation into Cancer and Nutrition (EPIC)
      Study) pc-program. SUBJECTS/METHODS: A total of 75 children aged 7-8 years and 70
      children aged 12-13 years old were recruited through the Civil Registration
      System in Denmark, and 57 children aged 7-8 years and 47 children aged 12-13
      years were recruited through schools in Spain. Each child with one parent
      completed two face-to-face 24-HDRs, combined with optional use of a food
      recording booklet (FRB) to be filled in by the child, a parent or other proxy
      persons for preparing the recalls. Feasibility was evaluated by questionnaires
      completed by parents, children and interviewers, and by selected data from the 24
      HDRs. RESULTS: The face-to-face interviews with the child and a parent together
      are confirmed as feasible. The children participated actively in the interviews,
      the oldest children being most active. The children, parents and interviewers
      agreed that children needed help from the parents, and that parents were of help
      to the child. In both countries, other proxy persons, such as teachers or the
      school cafeteria staff, were involved before the interview, and the majority of
      the parents and children reported that the FRB had been a help for the child
      during the interview. Further results point at specific needed improvements of
      the tools. CONCLUSIONS: The evaluated method is shown feasible in two culturally
      diverse European populations. However, the feasibility study also points to
      specific improvements of tools and data collection protocol that are strongly
      recommended before implementation of the method in each country of a pan-European
      dietary survey.

PMID- 21731009
TI  - Evaluation of 2 * 24-h dietary recalls combined with a food-recording booklet,
      against a 7-day food-record method among schoolchildren.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the estimated
      energy, nutrient and food intake from the suggested trans-European methodology
      for undertaking representative dietary surveys among schoolchildren: 2 * 24-h
      dietary recalls (24-HDRs) combined with a food-recording booklet (FRB), using
      EPIC-Soft pc-program (the software developed to conduct 24-HDRs in the European
      Prospective Investigation into Cancer and Nutrition (EPIC) Study), against a 7
      day food-record (7-dFR) method among Danish schoolchildren. SUBJECTS/METHODS: A
      total of 74 children aged 7-8 years and 70 children aged 12-13 years were
      recruited through the Civil Registration System in Denmark. Each child and one of
      their parents completed two face-to-face 24-HDRs, combined with optional use of a
      FRB, followed by a 7-day-estimated FR. RESULTS: Energy intake was significantly
      higher with the 24-HDR method than with the 7-dFR method for both age groups.
      Mean energy intake was 6% higher for the youngest (P = 0.02) and 11% for the
      oldest children (P = 0.01); underreporting of energy occurs among the oldest
      children, being less present with the 24-HDR method. The intakes of carbohydrate
      and dietary fiber (absolute and related to energy) were significantly higher with
      the 24-HDR than with the 7-dFR for both age groups (P < 0.001). No significant
      differences between the two methods were observed for absolute intake of fat and
      added sugar between both age groups, and for intake of protein among the 7- to 8
      year olds. The percentage of energy intake from fat from the 24-HDR, however, was
      significantly lower for both age groups and for energy intake from added sugar
      for the 12- to 13-year olds. CONCLUSIONS: The 2 * 24-HDR method compared with the
      7-dFR yields relatively good values on the group level for many macronutrients
      and foods. However, some differences in estimated intakes of macronutrients
      suggest the need to carefully adapt the tools to be age and country specific.
      There is a tendency for parents and schoolchildren to report a healthier diet
      with the 24-HDR than with the FRs; this results in some concern about the method
      and has to be studied further.

PMID- 21731010
TI  - Feasibility of repeated 24-h dietary recalls combined with a food-recording
      booklet, using EPIC-Soft, among preschoolers.
AB  - BACKGROUND/OBJECTIVES: This study evaluates the feasibility among preschoolers of
      the 2 * 24-h dietary recalls (24-HDRs) method combined with a food-recording
      booklet (FRB), using EPIC-Soft pc-program for the 24-HDR (the software developed
      to conduct 24-HDRs in the European Prospective Investigation into Cancer and
      Nutrition (EPIC) Study). SUBJECTS/METHODS: A total of 20 and 25 (4- to 5-year
      old) children were recruited, as a convenience sample, through worksites or day
      or healthcare in Denmark and Spain, respectively. One parent (or both parents
      together) completed two face-to-face 24-HDR, combined with an optional use of a
      FRB. Feasibility was evaluated by evaluation questionnaires completed by parents
      and interviewers. RESULTS: The face-to-face interviews were primarily conducted
      with the mothers. The FRB was used by 90% of the participants, and proxy persons,
      other than the parent, were also involved; involvement of proxy persons seems
      necessary in a majority of the recalls in both the countries. CONCLUSIONS: The
      results suggest that 2 * 24-HDR with one parent combined with a FRB is feasible
      for registering preschoolers' diet. An FRB and/or information from proxy persons,
      other than the parent, is needed for a majority of the parents. In future
      studies, it may be beneficial to develop the FRB more like a structured food
      record (FR), which might, in principle, change the method to a one-day FR method
      from more than a 24-HDR method. It is recommended then to further investigate the
      use of EPIC-Soft as a data-entry tool.

PMID- 21731011
TI  - The MSM program: web-based statistics package for estimating usual dietary intake
      using the Multiple Source Method.
AB  - BACKGROUND/OBJECTIVES: The Multiple Source Method (MSM) is a new statistical
      method for estimating usual dietary intake including episodically consumed foods
      on the basis of two or more short-term measurements such as 24-h dietary recalls.
      Optional information regarding habitual use or non-use of a food can be included
      as a covariate in the model estimating the intake, as well as a parameter for
      identifying consumers and non-consumers. The objective was to implement the MSM
      algorithms into an easy-to-use statistical program package. SUBJECTS/METHODS: The
      implementation was realized as a web-based application using the Perl application
      framework Catalyst. As the engine for the statistical calculations, the R system
      was used. To allow simultaneous use of the program by different users, a
      multiuser system with a resource bag pattern design was implemented. RESULTS: We
      established a software program that implements the algorithms of the MSM and
      allows interactive usage of the method, using standard web technologies. The
      program is hosted on a website established at the DIFE and can be accessed at
      https://nugo.dife.de/msm. The communication between users and the program web
      site is encrypted, securing transmitted data against unauthorized use. Users can
      interactively import several data sets, define the analysis model, review and
      export results and graphs. The use of the program is supported by online help and
      a user guide. CONCLUSIONS: The MSM website provides a program package that allows
      nutritional scientists to calculate usual dietary intakes by combining short-term
      and long-term measurements (multiple sources). It promotes simple access to the
      MSM to estimate usual food intake for individuals and populations.

PMID- 21731012
TI  - Comparing four methods to estimate usual intake distributions.
AB  - BACKGROUND/OBJECTIVES: The aim of this paper was to compare methods to estimate
      usual intake distributions of nutrients and foods. As 'true' usual intake
      distributions are not known in practice, the comparison was carried out through a
      simulation study, as well as empirically, by application to data from the
      European Food Consumption Validation (EFCOVAL) Study in which two 24-h dietary
      recalls (24-HDRs) and food frequency data were collected. The methods being
      compared were the Iowa State University Method (ISU), National Cancer Institute
      Method (NCI), Multiple Source Method (MSM) and Statistical Program for Age
      adjusted Dietary Assessment (SPADE). SUBJECTS/METHODS: Simulation data were
      constructed with varying numbers of subjects (n), different values for the Box
      Cox transformation parameter (lambda(BC)) and different values for the ratio of
      the within- and between-person variance (r(var)). All data were analyzed with the
      four different methods and the estimated usual mean intake and selected
      percentiles were obtained. Moreover, the 2-day within-person mean was estimated
      as an additional 'method'. These five methods were compared in terms of the mean
      bias, which was calculated as the mean of the differences between the estimated
      value and the known true value. The application of data from the EFCOVAL Project
      included calculations of nutrients (that is, protein, potassium, protein density)
      and foods (that is, vegetables, fruit and fish). RESULTS: Overall, the mean bias
      of the ISU, NCI, MSM and SPADE Methods was small. However, for all methods, the
      mean bias and the variation of the bias increased with smaller sample size,
      higher variance ratios and with more pronounced departures from normality.
      Serious mean bias (especially in the 95th percentile) was seen using the NCI
      Method when r(var) = 9, lambda(BC) = 0 and n = 1000. The ISU Method and MSM
      showed a somewhat higher s.d. of the bias compared with NCI and SPADE Methods,
      indicating a larger method uncertainty. Furthermore, whereas the ISU, NCI and
      SPADE Methods produced unimodal density functions by definition, MSM produced
      distributions with 'peaks', when sample size was small, because of the fact that
      the population's usual intake distribution was based on estimated individual
      usual intakes. The application to the EFCOVAL data showed that all estimates of
      the percentiles and mean were within 5% of each other for the three nutrients
      analyzed. For vegetables, fruit and fish, the differences were larger than that
      for nutrients, but overall the sample mean was estimated reasonably. CONCLUSIONS:
      The four methods that were compared seem to provide good estimates of the usual
      intake distribution of nutrients. Nevertheless, care needs to be taken when a
      nutrient has a high within-person variation or has a highly skewed distribution,
      and when the sample size is small. As the methods offer different features,
      practical reasons may exist to prefer one method over the other.

PMID- 21731014
TI  - Quality of care for gastrointestinal conditions: a primer for
      gastroenterologists.
AB  - The Institute of Medicine's publications To Err Is Human and Crossing the Quality
      Chasm publicized the widespread deficits in health-care quality. The quality of
      care for digestive diseases has not been evaluated comprehensively, although
      emerging literature suggests that the gap between recommended care and actual
      practice may be quite substantial. This paper reviews the history of, the
      rationale behind, and current work related to quality of care and quality
      improvement in the area of digestive diseases, with particular attention to
      colonoscopy, inflammatory bowel diseases, gastroesophageal reflux disease,
      chronic hepatitis C virus infection, and liver transplantation.

PMID- 21731015
TI  - Intra-abdominal fungal infections complicating acute pancreatitis: a review.
AB  - Intra-abdominal infections of pancreatic or peripancreatic necrotic tissue
      complicate the clinical course of severe acute pancreatitis (SAP) and are
      associated with significant morbidity. Fungal infection of necrotic pancreatic
      tissue is increasingly being reported. The incidence of intra-abdominal
      pancreatic fungal infection (PFI) varies from 5% to 68.5%. Candida albicans is
      the most frequently isolated fungus in patients with necrotizing pancreatitis.
      Prolonged use of prophylactic antibiotics, prolonged placement of chronic
      indwelling devices, and minimally invasive or surgical interventions for
      pancreatic fluid collections further increase the risk of PFI. Computed
      tomography- or ultrasound-guided fine-needle aspiration of pancreatic necrosis is
      a safe, reliable method for establishing pancreatic infection. Amphotericin B
      appears to be the most effective antifungal treatment. Drainage and debridement
      of infected necrosis are also critical for eradication of fungi from the poorly
      perfused pancreatic or peripancreatic tissues where the antifungal agents may not
      reach to achieve therapeutic levels. Fungal infection adversely affects the
      outcome of patients with SAP and is associated with increased morbidity, although
      the mortality rate is not increased specifically because of PFI. Although
      antifungal prophylaxis has been suggested for patients on broad-spectrum
      antibiotics, no randomized controlled trials have yet studied its efficacy in
      preventing PFI.

PMID- 21731016
TI  - Screening colonoscopy in the underserved population: report of the first year of
      a no-cost colorectal cancer screening program for the underserved in Rhode
      Island.

PMID- 21731021
TI  - The incidence of esophageal adenocarcinoma in Barrett's esophagus has been
      overestimated.

PMID- 21731023
TI  - To scope or not to scope? A doctored version of Hamlet's Soliloquy.

PMID- 21731024
TI  - Response to Bolino et al.

PMID- 21731026
TI  - Drug regulatory agencies' role in the interaction between clopidogrel and proton
      pump inhibitors.

PMID- 21731025
TI  - Celiac disease detected by pouch biopsy of a patient with ileal pouch-anal
      anastomosis.

PMID- 21731027
TI  - The IL-28B genotype predicts which slow-responding hepatitis C-infected patients
      will benefit from treatment extension.

PMID- 21731032
TI  - Cortical substrate oxidation during hyperketonemia in the fasted anesthetized rat
      in vivo.
AB  - Ketone bodies are important alternate brain fuels, but their capacity to replace
      glucose and support neural function is unclear. In this study, the contributions
      of ketone bodies and glucose to cerebral cortical metabolism were measured in
      vivo in halothane-anesthetized rats fasted for 36 hours (n=6) and receiving
      intravenous [2,4-(13)C(2)]-D-beta-hydroxybutyrate (BHB). Time courses of (13)C
      enriched brain amino acids (glutamate-C4, glutamine-C4, and glutamate and
      glutamine-C3) were measured at 9.4 Tesla using spatially localized (1)H-[(13)C]
      nuclear magnetic resonance spectroscopy. Metabolic rates were estimated by
      fitting a constrained, two-compartment (neuron-astrocyte) metabolic model to the
      (13)C time-course data. We found that ketone body oxidation was substantial,
      accounting for 40% of total substrate oxidation (glucose plus ketone bodies) by
      neurons and astrocytes. D-beta-Hydroxybutyrate was oxidized to a greater extent
      in neurons than in astrocytes (~ 70:30), and followed a pattern closely similar
      to the metabolism of [1-(13)C]glucose reported in previous studies. Total
      neuronal tricarboxylic acid cycle (TCA) flux in hyperketonemic rats was similar
      to values reported for normal (nonketotic) anesthetized rats infused with [1
      (13)C]glucose, but neuronal glucose oxidation was 40% to 50% lower, indicating
      that ketone bodies had compensated for the reduction in glucose use.

PMID- 21731033
TI  - Metabotropic glutamate receptor mGluR5 is not involved in the early hemodynamic
      response.
AB  - Activation of astrocytic metabotropic glutamate receptor 5 (mGluR5) is postulated
      to elicit calcium transients, triggering a chain of events that ultimately
      regulates cerebral blood flow by changing the tone of smooth muscle cells of
      nearby arterioles. Using concurrent in vivo optical imaging and determination of
      receptor occupancy with (11)C-ABP688, we report here that blocking ~80% of mGluR5
      in vivo does not affect transient hemodynamic responses on brief whisker
      stimulations while transiently reducing neuronal activity as measured by voltage
      sensitive dye imaging. Our results show that mechanisms other than activation of
      mGluR5 are required to trigger the initial hemodynamic response in normal
      physiological conditions.

PMID- 21731034
TI  - Heterogeneity in the penumbra.
AB  - Original experimental studies in nonhuman primate models of focal ischemia showed
      flow-related changes in evoked potentials that suggested a circumferential zone
      of low regional cerebral blood flow with normal K(+) homeostasis, around a core
      of permanent injury in the striatum or the cortex. This became the basis for the
      definition of the ischemic penumbra. Imaging techniques of the time suggested a
      homogeneous core of injury, while positing a surrounding 'penumbral' region that
      could be salvaged. However, both molecular studies and observations of vascular
      integrity indicate a more complex and dynamic situation in the ischemic core that
      also changes with time. The microvascular, cellular, and molecular events in the
      acute setting are compatible with heterogeneity of the injury within the injury
      center, which at early time points can be described as multiple 'mini-cores'
      associated with multiple 'mini-penumbras'. These observations suggest the
      progression of injury from many small foci to a homogeneous defect over time
      after the onset of ischemia. Recent observations with updated imaging techniques
      and data processing support these dynamic changes within the core and the
      penumbra in humans following focal ischemia.

PMID- 21731035
TI  - Vitamin D and type 2 diabetes: a systematic review.
AB  - BACKGROUND/OBJECTIVES: Vitamin D may modify the risk of type 2 diabetes mellitus.
      The aim of this review was to examine the association between vitamin D status
      and incident type 2 diabetes, and the effect of vitamin D supplementation on
      glycemic outcomes. METHODS: We performed a systematic review of English-language
      studies using MEDLINE through February 2011. Longitudinal cohort studies
      reporting associations between vitamin D status and incident type 2 diabetes, and
      randomized controlled trials (RCTs) of vitamin D supplementation, were included.
      Study characteristics and results were extracted, and study quality was assessed.
      RESULTS: A total of 8 observational cohort studies and 11 RCTs were included. In
      meta-analyses of observational studies, vitamin D intake>500 international units
      (IU)/day decreased the risk of type 2 diabetes by 13% compared with vitamin D
      intake<200 IU/day. Individuals with the highest vitamin D status (>25 ng/ml) had
      a 43% lower risk of developing type 2 diabetes (95% confidence interval 24, 57%)
      compared with those in the lowest group (<14 ng/ml). In post hoc analyses from
      eight trials among participants with normal glucose tolerance at baseline and in
      three small underpowered (n=32-62) trials of patients with established type 2
      diabetes, there was no effect of vitamin D supplementation on glycemic outcomes.
      In two trials among patients with baseline glucose intolerance, vitamin D
      supplementation improved insulin resistance. CONCLUSIONS: Vitamin D may play a
      role in type 2 diabetes; however, to better define the role of vitamin D in the
      development and progression of type 2 diabetes, high-quality observational
      studies and RCTs that measure blood 25-hydroxyvitamin D concentration and
      clinically relevant glycemic outcomes are needed.

PMID- 21731036
TI  - An estimate of the global reduction in mortality rates through doubling vitamin D
      levels.
AB  - BACKGROUND/OBJECTIVES: The goal of this work is to estimate the reduction in
      mortality rates for six geopolitical regions of the world under the assumption
      that serum 25-hydroxyvitamin D (25(OH)D) levels increase from 54 to 110 nmol/l.
      SUBJECTS/METHODS: This study is based on interpretation of the journal literature
      relating to the effects of solar ultraviolet-B (UVB) and vitamin D in reducing
      the risk of disease and estimates of the serum 25(OH)D level-disease risk
      relations for cancer, cardiovascular disease (CVD) and respiratory infections.
      The vitamin D-sensitive diseases that account for more than half of global
      mortality rates are CVD, cancer, respiratory infections, respiratory diseases,
      tuberculosis and diabetes mellitus. Additional vitamin D-sensitive diseases and
      conditions that account for 2 to 3% of global mortality rates are Alzheimer's
      disease, falls, meningitis, Parkinson's disease, maternal sepsis, maternal
      hypertension (pre-eclampsia) and multiple sclerosis. Increasing serum 25(OH)D
      levels from 54 to 110 nmol/l would reduce the vitamin D-sensitive disease
      mortality rate by an estimated 20%. RESULTS: The reduction in all-cause mortality
      rates range from 7.6% for African females to 17.3% for European females.
      Reductions for males average 0.6% lower than for females. The estimated increase
      in life expectancy is 2 years for all six regions. CONCLUSIONS: Increasing serum
      25(OH)D levels is the most cost-effective way to reduce global mortality rates,
      as the cost of vitamin D is very low and there are few adverse effects from oral
      intake and/or frequent moderate UVB irradiance with sufficient body surface area
      exposed.

PMID- 21731037
TI  - Vitamin D: the light side of sunshine.
AB  - Under normal circumstances, vitamin D is mainly obtained from skin through the
      action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further
      metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D
      compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major
      function of vitamin D compounds is to enhance active absorption of ingested
      calcium (and phosphate). This assists in building bone at younger ages and
      ensures that despite obligatory urinary losses, bone does not need to be resorbed
      to maintain blood calcium concentrations. Vitamin D compounds appear to have
      direct effects to improve bone and muscle function, and there is good, although
      not entirely consistent, evidence that supplemental vitamin D and calcium
      together reduce falls and fractures in older individuals. On the basis of calcium
      control and musculoskeletal function, target levels for 25OHD in blood are at
      least 50-60 nmol/l and there may be a case for higher targets of 75-80 nmol/l.
      There are vitamin D receptors in most nucleated cells and some evidence, although
      not consistent, that adequate vitamin D levels may be important in reducing the
      incidence of, or mortality from, some cancers and in reducing autoimmune disease.
      Adequate vitamin D may also allow for a normal innate immune response to
      pathogens, improve cardiovascular function and mortality and increase insulin
      responsiveness. Vitamin D levels are maintained better in the presence of
      adequate calcium intakes, more exercise and less obesity. Genetic variation may
      have an effect on vitamin D blood levels and response to treatment with vitamin
      D.

PMID- 21731038
TI  - Calcium and vitamin D for obesity: a review of randomized controlled trials.
AB  - Obesity often coexists with low calcium intake and vitamin D insufficiency. There
      is emerging evidence of a role for these nutrients in the regulation of body
      weight. However, it is unclear whether increasing intakes of calcium and/or
      vitamin D during energy restriction, is a better strategy for weight and fat
      loss. We searched the literature from 2000 to date for randomized controlled
      trials (RCTs) on weight loss that had increased calcium or vitamin D per se, or
      in combination. Primary and secondary studies were included for this analysis. A
      total of 15 RCTs on calcium with or without vitamin D and seven on vitamin D
      alone met our criteria. Two studies reported that supplemental calcium
      significantly increased fat loss during caloric restriction by 1.8 and 2.2 kg,
      three found differences between 1 and 3.5 kg but were statistically
      nonsignificant, while nine trials were equivocal (+/-0.7 kg). The data on vitamin
      D supplementation during weight loss were too few to make firm conclusions.
      Current evidence from RCTs did not consistently support the contention that
      calcium and vitamin D accelerated weight or fat loss in obesity. There were
      studies that favoured the hypothesis but lacked the statistical power. There is a
      need for RCTs to examine the influence of vitamin D on body fat.

PMID- 21731039
TI  - Prediction of body-fat percentage from skinfold and bio-impedance measurements in
      Indian school children.
AB  - BACKGROUND/OBJECTIVES: Few equations for calculating body-fat percentage (BF%)
      from field methods have been developed in South-Asian children. The objective of
      this study was to assess agreement between BF% derived from primary reference
      methods and that from skinfold equations and bio-impedance analysis (BIA) in
      Indian children. SUBJECTS/METHODS: We measured BF% in two groups of Indian
      children. In Pune, 570 rural children aged 6-8 years underwent dual-energy X-ray
      absorptiometry (DXA) scans. In Mysore (18)O in doubly labeled water was
      administered to 59 urban children aged 7-9 years. We conducted BIA at 50 kHz and
      anthropometry, including sub-scapular and triceps skinfold thicknesses. We used
      the published equations of Wickramasinghe, Shaikh, Slaughter and Dezenburg to
      calculate BF% from anthropometric data and the manufacturer's equation for BIA
      measurements. We assessed agreement with values derived from DXA and doubly
      labeled water using Bland-Altman analysis. RESULTS: Children were light and thin
      on average compared with international standards. There was poor agreement
      between the reference BF% values and those from all equations. Assumptions for
      Bland-Altman analysis were not met for Wickramasinghe, Shaikh and Slaughter
      equations. The Dezenberg equations under-predicted BF% for most children (mean
      difference in Pune -13.4, LOA -22.7, -4.0 and in Mysore -7.9, LOA (-13.7 and 
      2.2). The mean bias for the BIA equation in Pune was +5.0% and in Mysore +1.95%,
      and the limits of agreement were wide; -5.0, 15.0 and -7.8, 11.7 respectively.
      CONCLUSIONS: Currently available skinfold equations do not accurately predict BF%
      in Indian children. We recommend development of BIA equations in this population
      using a four-compartment model.

PMID- 21731040
TI  - Relationship of intake of plant-based foods with 6-n-propylthiouracil sensitivity
      and food neophobia in Japanese preschool children.
AB  - BACKGROUND/OBJECTIVES: Diets rich in plant-based foods such as vegetables, fruits
      and soy foods have been suggested to have beneficial effects on health. However,
      phytochemicals contained in plant-based foods are generally bitter and acrid. We
      investigated whether intake of vegetables, fruits and soy foods is associated
      with sensitivity to bitterness and reluctance to eat new foods (food neophobia)
      in Japanese preschool children. SUBJECTS/METHODS: Subjects of this cross
      sectional study were healthy Japanese, 167 boys and 156 girls, aged 4-6 years.
      Intake of vegetables, fruits and soy foods was estimated from 3-day dietary
      records. Subjects were classified as either tasters or non-tasters of 6-n
      propylthiouracil (PROP) based on their ability to taste 0.56 mmol/l PROP.
      Information on each child's age, height, weight, food neophobia status and food
      variety, as well as maternal diet and parental control over the child's eating,
      was obtained by a parent-administered questionnaire. Food neophobia was assessed
      using the Child Food Neophobia Scale (CFNS). RESULTS: A high intake of vegetables
      was significantly associated with a low CFNS score in boys after controlling for
      covariates (P=0.0008). Among the boys, soy food intake was significantly higher
      in PROP non-tasters than in tasters, except those with low CFNS scores
      (P=0.0019). High intake of soy foods was significantly associated with a low
      neophobia score in PROP tasters but not in non-tasters (P=0.0024). CONCLUSIONS:
      These data suggest that sensitivity to bitter taste and food neophobia may
      influence the consumption of vegetables and soy foods among Japanese preschool
      boys.

PMID- 21731041
TI  - Validation of bioelectrical impedance analysis for total body water assessment
      against the deuterium dilution technique in Asian children.
AB  - BACKGROUND/OBJECTIVES: To develop and cross-validate bioelectrical impedance
      analysis (BIA) prediction equations of total body water (TBW) and fat-free mass
      (FFM) for Asian pre-pubertal children from China, Lebanon, Malaysia, Philippines
      and Thailand. SUBJECTS/METHODS: Height, weight, age, gender, resistance and
      reactance measured by BIA were collected from 948 Asian children (492 boys and
      456 girls) aged 8-10 years from the five countries. The deuterium dilution
      technique was used as the criterion method for the estimation of TBW and FFM. The
      BIA equations were developed using stepwise multiple regression analysis and
      cross-validated using the Bland-Altman approach. RESULTS: The BIA prediction
      equation for the estimation of TBW was as follows: TBW=0.231 *
      height(2)/resistance+0.066 * height+0.188 * weight+0.128 * age+0.500 * sex-0.316
      * Thais-4.574 (R (2)=88.0%, root mean square error (RMSE)=1.3 kg), and for the
      estimation of FFM was as follows: FFM=0.299 * height(2)/resistance+0.086 *
      height+0.245 * weight+0.260 * age+0.901 * sex-0.415 * ethnicity (Thai ethnicity
      =1, others = 0)-6.952 (R (2)=88.3%, RMSE=1.7 kg). No significant difference
      between measured and predicted values for the whole cross-validation sample was
      found. However, the prediction equation for estimation of TBW/FFM tended to
      overestimate TBW/FFM at lower levels whereas underestimate at higher levels of
      TBW/FFM. Accuracy of the general equation for TBW and FFM was also valid at each
      body mass index category. CONCLUSIONS: Ethnicity influences the relationship
      between BIA and body composition in Asian pre-pubertal children. The newly
      developed BIA prediction equations are valid for use in Asian pre-pubertal
      children.

PMID- 21731042
TI  - Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since
      1959: potential implications for folate requirements.
AB  - BACKGROUND/OBJECTIVES: Folate has been recognized to ensure reproductive health
      and there is a growing body of epidemiological evidence suggesting that the
      methylenetetrahydrofolate reductase (MTHFR) 677T allele and reduced dietary
      folate may increase the risk of cervical cancer. The main focus of our survey was
      to investigate the distribution of the MTHFR C677T polymorphism in relation to
      women's year of birth and to assess their folate intake and folic acid
      supplementation. SUBJECTS/METHODS: During a 6-months period, 307 healthy women of
      childbearing age in Catania, Italy, were enrolled in the cross-sectional study.
      Folate intake was estimated by a semiquantitative food frequency questionnaire
      and DNA extracted from blood samples for MTHFR C677T genotyping. RESULTS: A TT
      genotype frequency of 20.5% with an increase in the prevalence of the TT genotype
      in the cohort of women born since 1959 was shown. The prevalence of inadequate
      folate intake was 51.5%, significantly higher in non-pregnant women (83.4%) than
      in pregnant ones (12.3%) with a decrease during the three trimesters of pregnancy
      (from 25.7 to 5.0%; P=0.013). The use of folic acid supplements improved during
      the three trimester of pregnancy (from 71.4 to 95.0%; P=0.001). CONCLUSIONS:
      Healthy young women may have higher folate needs due to increasing prevalence of
      the T allele and reduced folate intake compared with older groups. However,
      clinicians should be cautious when recommending supplements to women in late
      pregnancy due to the possible implications in the pregnancy outcome.

PMID- 21731043
TI  - A comparison of two screening methods to determine the validity of 24-h food and
      drink records in children and adolescents.
AB  - BACKGROUND/OBJECTIVES: Dietary assessment in humans is hampered by the phenomena
      of under and overreporting of energy intake, when food records are used to
      evaluate habitual dietary intake. Different methods to evaluate mis-reporting
      have been proposed using cut-offs derived from estimates of reported energy
      intake and basal metabolic rate, or, from predictions of total energy
      expenditure. This study compares the effect of using two different cut-off
      approaches to screen food records for validity, completed by a large cohort of
      Australian children (n=2460), from Grades 1, 5 and 10 (aged 5-17 years).
      SUBJECTS/METHODS: Energy intake was calculated from 24-h food and drink records
      for each child. These data were screened using the Goldberg and McCrory cut-offs.
      The effect of using these two cut-offs on the collected dataset was explored by
      considering the mean and standard deviation of energy intake in each year level
      before and after the cut-offs were applied. RESULTS: The use of the Goldberg cut
      off resulted in 9% of the total cohort being classified as underreporters, with
      60% of these subjects being in Grade 10. The McCrory cut-offs revealed that
      overall, 22% of the total cohort underreported EI. 33.3% of Grade 1 children were
      classified as overreporters with this value falling to about 20% of Grade 10
      children, while 10-15% of Grade 1 children underreported, with this figure rising
      to about 30% in Grade 10. CONCLUSIONS: Both the Goldberg and McCrory approaches
      have their advantages and disadvantages, and we suggest that consideration should
      be given to the reason for screening data before a particular approach is used,
      with recognition that these methods do differ in their aims and outcomes. The
      McCrory method consistently classified a greater number of children as
      underreporters.

PMID- 21731044
TI  - Mutually reinforcing patterning mechanisms.

PMID- 21731046
TI  - Arresting times for PTEN.

PMID- 21731047
TI  - From DNA binding to metabolic control: integration of -omics data reveals drug
      targets for prostate cancer.

PMID- 21731048
TI  - Understanding cargo specificity in intraflagellar transport.

PMID- 21731052
TI  - High rate of calculation errors in mismatch distribution analysis results in
      numerous false inferences of biological importance.

PMID- 21731053
TI  - Towards the genetic architecture of seed lipid biosynthesis and accumulation in
      Arabidopsis thaliana.
AB  - We report the quantitative genetic analysis of seed oil quality and quantity in
      six Arabidopsis thaliana recombinant inbred populations, in which the parent
      accessions were from diverse geographical origins, and were selected on the basis
      of variation for seed oil content and lipid composition. Although most of the
      biochemical steps involved in lipid biosynthesis are known and the key genes have
      been identified, the regulation of the processes that results in the final oil
      composition and total amount is not understood. By using physically anchored
      markers it was possible to compare results across populations. A total of 219
      quantitative trait loci (QTLs) were identified, of which 81 were significant at
      P<0.001. Some of these colocalise with QTLs identified previously, but many novel
      QTLs were also identified. The results highlight the importance of studying
      traits in multiple populations, which will lead to a better understanding of the
      contribution that natural variation makes to the genetic architecture of a
      phenotype.

PMID- 21731054
TI  - Variation for host range within and among populations of the parasitic plant
      Striga hermonthica.
AB  - Striga hermonthica is an angiosperm parasite that causes substantial damage to a
      wide variety of cereal crop species, and to the livelihoods of subsistence
      farmers in sub-Saharan Africa. The broad host range of this parasite makes it a
      fascinating model for the study of host-parasite interactions, and suggests that
      effective long-term control strategies for the parasite will require an
      understanding of the potential for host range adaptation in parasite populations.
      We used a controlled experiment to test the extent to which the success or
      failure of S. hermonthica parasites to develop on a particular host cultivar
      (host resistance/compatibility) depends upon the identity of interacting host
      genotypes and parasite populations. We also tested the hypothesis that there is a
      genetic component to host range within individual S. hermonthica populations,
      using three rice cultivars with known, contrasting abilities to resist infection.
      The developmental success of S. hermonthica parasites growing on different rice
      host cultivars (genotypes) depended significantly on a parasite population by
      host-genotype interaction. Genetic analysis using amplified fragment length
      polymorphism (AFLP) markers revealed that a small subset of AFLP markers showed
      'outlier' genetic differentiation among sub-populations of S. hermonthica
      attached to different host cultivars. We suggest that, this indicates a genetic
      component to host range within populations of S. hermonthica, and that a detailed
      understanding of the genomic loci involved will be crucial in understanding host
      parasite specificity and in breeding crop cultivars with broad spectrum
      resistance to S. hermonthica.

PMID- 21731055
TI  - Worldwide genetic structure in 37 genes important in telomere biology.
AB  - Telomeres form the ends of eukaryotic chromosomes and are vital in maintaining
      genetic integrity. Telomere dysfunction is associated with cancer and several
      chronic diseases. Patterns of genetic variation across individuals can provide
      keys to further understanding the evolutionary history of genes. We investigated
      patterns of differentiation and population structure of 37 telomere maintenance
      genes among 53 worldwide populations. Data from 898 unrelated individuals were
      obtained from the genome-wide scan of the Human Genome Diversity Panel (HGDP) and
      from 270 unrelated individuals from the International HapMap Project at 716
      single-nucleotide polymorphism (SNP) loci. We additionally compared this gene set
      to HGDP data at 1396 SNPs in 174 innate immunity genes. The majority of the
      telomere biology genes had low to moderate haplotype diversity (45-85%), high
      ancestral allele frequencies (>60%) and low differentiation (FST<0.10).
      Heterozygosity and differentiation were significantly lower in telomere biology
      genes compared with the innate immunity genes. There was evidence of evolutionary
      selection in ACD, TERF2IP, NOLA2, POT1 and TNKS in this data set, which was
      consistent in HapMap 3. TERT had higher than expected levels of haplotype
      diversity, likely attributable to a lack of linkage disequilibrium, and a
      potential cancer-associated SNP in this gene, rs2736100, varied substantially in
      genotype frequency across major continental regions. It is possible that the
      genes under selection could influence telomere biology diseases. As a group,
      there appears to be less diversity and differentiation in telomere biology genes
      than in genes with different functions, possibly due to their critical role in
      telomere maintenance and chromosomal stability.

PMID- 21731056
TI  - Data-driven approach to detect common copy-number variations and frequency
      profiles in a population-based Korean cohort.
AB  - To date, hundreds of thousands of copy-number variation (CNV) data have been
      reported using various platforms. The proportion of Asians in these data is,
      however, relatively small as compared with that of other ethnic groups, such as
      Caucasians and Yorubas. Because of limitations in platform resolution and the
      high noise level in signal intensity, in most CNV studies (particularly those
      using single nucleotide polymorphism arrays), the average number of CNVs in an
      individual is less than the number of known CNVs. In this study, we ascertained
      reliable, common CNV regions (CNVRs) and identified actual frequency rates in the
      Korean population to provide more CNV information. We performed two-stage
      analyses for detecting structural variations with two platforms. We discovered
      576 common CNVRs (88 CNV segments on average in an individual), and 87% (501 of
      576) of these CNVRs overlapped by >=1 bp with previously validated CNV events.
      Interestingly, from the frequency analysis of CNV profiles, 52 of 576 CNVRs had a
      frequency rate of <1% in the 8842 individuals. Compared with other common CNV
      studies, this study found six common CNVRs that were not reported in previous CNV
      studies. In conclusion, we propose the data-driven detection approach to discover
      common CNVRs including those of unreported in the previous Korean CNV study while
      minimizing false positives. Through our approach, we successfully discovered more
      common CNVRs than previous Korean CNV study and conducted frequency analysis.
      These results will be a valuable resource for the effective level of CNVs in the
      Korean population.

PMID- 21731057
TI  - Initial interrogation, confirmation and fine mapping of modifying genes: STAT3,
      IL1B and IFNGR1 determine cystic fibrosis disease manifestation.
AB  - We have used a stepwise approach consisting of initial interrogation,
      confirmation and fine mapping to analyze STAT3, IL1B and IFNGR1 as modifiers of
      cystic fibrosis disease building upon the data and sample collection of the
      European Cystic Fibrosis Twin and Sibling Study. We have observed direct
      correlation between the length of the intronic microsatellite STAT3Sat to STAT3
      expression levels among F508del-CFTR homozygous patients (P=0.0075), and an
      association of longer STAT3Sat-alleles with the presence of CFTR-mediated
      residual chloride secretion (P=0.0031), measured as the manifestation of the CF
      basic defect in intestinal tissue. Both, family-based analysis by TDT and case
      reference comparison identified consistently the same intragenic IL1B haplotype
      as a risk variant (P(raw)=0.055 for TDT, P(raw)<0.3 for case-reference
      comparison). Using haplotype-guided hierarchical fine mapping, we have identified
      two single nucleotide exchanges for which concordant and discordant sibling pairs
      differ at a 7 kb-spanning core haplotype in IFNGR1 (P(raw)=0.0113). Taken
      together, our findings imply that immunorelevant pathways and ion secretion,
      dominated by CFTR in intestinal and respiratory epithelium, merge at the level of
      the epithelial cell to integrate the signaling of cytokines due to innate and
      acquired immune defense.

PMID- 21731058
TI  - The potential influence of KIR cluster profiles on disease patterns of Canadian
      Aboriginals and other indigenous peoples of the Americas.
AB  - Genetic differences in immune regulators influence disease resistance and
      susceptibility patterns. There are major health discrepancies in immune-mediated
      diseases between Caucasians and Canadian Aboriginal people, as well as with other
      indigenous people of the Americas. Environmental factors offer a limited
      explanation as Aboriginal people also demonstrate a rare resistance to chronic
      hepatitis C virus infection. Killer immunoglobulin-like receptors (KIRs) are
      known modulators of viral responses and autoimmune diseases. The possibility that
      variation in KIR cluster profiles contribute to the health outcomes of Aboriginal
      people was evaluated with Canadian Caucasian (n=93, population controls) and
      Aboriginal (n=86) individuals. Relative to Caucasians, the Aboriginal KIR cluster
      displayed a greater immune activating phenotype associated with genes of the B
      haplotype situated within the telomeric region. In conjunction, there was a
      decrease in the genes of the B haplotype from the centromeric region. Caucasian
      and Aboriginal cohorts further demonstrated distinct genotype and haplotype
      relationships enforcing the disconnect between the B haplotype centromeric and
      telomeric regions within the Aboriginal population. Moreover, Caucasian KIR
      cluster patterns reflected studies of Caucasians globally, as well as Asians. In
      contrast, the unique pattern of the Canadian Aboriginal cohort mirrored the
      phenotype of other indigenous peoples of the Americas, but not that of Caucasians
      or Asians. Taken together, these data suggest that historically indigenous
      peoples of the Americas were subject to immune selection processes that could be
      influencing the current disease resistance and susceptibility patterns of their
      descendents.

PMID- 21731059
TI  - Motivators for participation in a whole-genome sequencing study: implications for
      translational genomics research.
AB  - The promise of personalized medicine depends on the ability to integrate genetic
      sequencing information into disease risk assessment for individuals. As genomic
      sequencing technology enters the realm of clinical care, its scale necessitates
      answers to key social and behavioral research questions about the complexities of
      understanding, communicating, and ultimately using sequence information to
      improve health. Our study captured the motivations and expectations of research
      participants who consented to participate in a research protocol, ClinSeq, which
      offers to return a subset of the data generated through high-throughput
      sequencing. We present findings from an exploratory study of 322 participants,
      most of whom identified themselves as white, non-Hispanic, and coming from higher
      socio-economic groups. Participants aged 45-65 years answered open-ended
      questions about the reasons they consented to ClinSeq and about what they
      anticipated would come of genomic sequencing. Two main reasons for participating
      were as follows: a conviction to altruism in promoting research, and a desire to
      learn more about genetic factors that contribute to one's own health risk.
      Overall, participants expected genomic research to help improve understanding of
      disease causes and treatments. Our findings offer a first glimpse into the
      motivations and expectations of individuals seeking their own genomic
      information, and provide initial insights into the value these early adopters of
      technology place on information generated by high-throughput sequencing studies.

PMID- 21731060
TI  - A novel locus for autosomal dominant congenital cerulean cataract maps to
      chromosome 12q.
AB  - Cataracts are the commonest cause of blindness worldwide. Inherited cataract is a
      clinically and genetically heterogeneous disease that most often shows autosomal
      dominant inheritance. In this study, we report the identification of a novel
      locus for cerulean cataract type 5 (CCA5), also known as blue-dot cataract on
      chromosome 12q24. To date, four loci for autosomal dominant congenital cerulean
      cataract have been mapped on chromosomes, 17q24, 22q11.2-12.2, 2q33-35 and
      16q23.1. To map this locus we performed genetic linkage analysis using
      microsatellite markers in a five-generation English family. After the exclusion
      of all known loci and several candidate genes we obtained significantly positive
      LOD score (Z) for marker D12S1611 (Z(max)=3.60; at theta=0). Haplotype data
      indicated that CCA5 locus lies within a region of 14.3 Mb interval between the
      markers D12S1718 and D12S1723. Our data are strongly suggestive of a new locus
      for CCA5 on chromosome 12.

PMID- 21731061
TI  - CGene: an R package for implementation of causal genetic analyses.
AB  - The excitement over findings from Genome-Wide Association Studies (GWASs) has
      been tempered by the difficulty in finding the location of the true causal
      disease susceptibility loci (DSLs), rather than markers that are correlated with
      the causal variants. In addition, many recent GWASs have studied multiple
      phenotypes--often highly correlated--making it difficult to understand which
      associations are causal and which are seemingly causal, induced by phenotypic
      correlations. In order to identify DSLs, which are required to understand the
      genetic etiology of the observed associations, statistical methodology has been
      proposed that distinguishes between a direct effect of a genetic locus on the
      primary phenotype and an indirect effect induced by the association with the
      intermediate phenotype that is also correlated with the primary phenotype.
      However, so far, the application of this important methodology has been
      challenging, as no user-friendly software implementation exists. The lack of
      software implementation of this sophisticated methodology has prevented its large
      scale use in the genetic community. We have now implemented this statistical
      approach in a user-friendly and robust R package that has been thoroughly tested.
      The R package 'CGene' is available for download at http://cran.r-project.org/.
      The R code is also available at http://people.hsph.harvard.edu/~plipman.

PMID- 21731062
TI  - Reduced dietary salt for the prevention of cardiovascular disease: a meta
      analysis of randomized controlled trials (Cochrane review).
AB  - BACKGROUND: Although meta-analyses of randomized controlled trials (RCTs) of salt
      reduction report a reduction in the level of blood pressure (BP), the effect of
      reduced dietary salt on cardiovascular disease (CVD) events remains unclear.
      METHODS: We searched for RCTs with follow-up of at least 6 months that compared
      dietary salt reduction (restricted salt dietary intervention or advice to reduce
      salt intake) to control/no intervention in adults, and reported mortality or CVD
      morbidity data. Outcomes were pooled at end of trial or longest follow-up point.
      RESULTS: Seven studies were identified: three in normotensives, two in
      hypertensives, one in a mixed population of normo- and hypertensives and one in
      heart failure. Salt reduction was associated with reductions in urinary salt
      excretion of between 27 and 39 mmol/24 h and reductions in systolic BP between 1
      and 4 mm Hg. Relative risks (RRs) for all-cause mortality in normotensives
      (longest follow-up-RR: 0.90, 95% confidence interval (CI): 0.58-1.40, 79 deaths)
      and hypertensives (longest follow-up RR 0.96, 0.83-1.11, 565 deaths) showed no
      strong evidence of any effect of salt reduction CVD morbidity in people with
      normal BP (longest follow-up: RR 0.71, 0.42-1.20, 200 events) and raised BP at
      baseline (end of trial: RR 0.84, 0.57-1.23, 93 events) also showed no strong
      evidence of benefit. Salt restriction increased the risk of all-cause mortality
      in those with heart failure (end of trial RR 2.59, 1.04-6.44, 21 deaths).We found
      no information on participant's health-related quality of life. CONCLUSIONS:
      Despite collating more event data than previous systematic reviews of RCTs (665
      deaths in some 6,250 participants) there is still insufficient power to exclude
      clinically important effects of reduced dietary salt on mortality or CVD
      morbidity. Our estimates of benefits from dietary salt restriction are consistent
      with the predicted small effects on clinical events attributable to the small BP
      reduction achieved.

PMID- 21731063
TI  - The Cochrane review of sodium and health.

PMID- 21731065
TI  - Unraveling the mechanism of BRCA2 in homologous recombination.
AB  - BRCA2 is the product of a breast cancer susceptibility gene in humans and the
      founding member of an emerging family of proteins present throughout the
      eukaryotic domain that serve in homologous recombination. The function of BRCA2
      in recombination is to control RAD51, a protein that catalyzes homologous pairing
      and DNA strand exchange. By physically interacting with both RAD51 and single
      stranded DNA, BRCA2 mediates delivery of RAD51 preferentially to sites of single
      stranded DNA (ssDNA) exposed as a result of DNA damage or replication problems.
      Through its action, BRCA2 helps restore and maintain integrity of the genome.
      This review highlights recent studies on BRCA2 and its orthologs that have begun
      to illuminate the molecular mechanisms by which these proteins control homologous
      recombination.

PMID- 21731066
TI  - Neural mechanisms of the cognitive model of depression.
AB  - In the 40 years since Aaron Beck first proposed his cognitive model of
      depression, the elements of this model--biased attention, biased processing,
      biased thoughts and rumination, biased memory, and dysfunctional attitudes and
      schemas--have been consistently linked with the onset and maintenance of
      depression. Although numerous studies have examined the neural mechanisms that
      underlie the cognitive aspects of depression, their findings have not been
      integrated with Beck's cognitive model. In this Review, we identify the
      functional and structural neurobiological architecture of Beck's cognitive model
      of depression. Although the mechanisms underlying each element of the model
      differ, in general the negative cognitive biases in depression are facilitated by
      increased influence from subcortical emotion processing regions combined with
      attenuated top-down cognitive control.

PMID- 21731067
TI  - Why not zwergo-technology?

PMID- 21731069
TI  - Metamaterials: a stamp of quality.

PMID- 21731070
TI  - Nanobiotechnology: building a basic nanomachine.

PMID- 21731071
TI  - Scanning probes: cold-atom microscope shapes up.

PMID- 21731072
TI  - Condensed matter physics: superconductivity at the double.

PMID- 21731073
TI  - Chronic exposure to toluene changes the sleep-wake pattern and brain monoamine
      content in rats.
AB  - Toluene, found in glues and cleaners, is among the inhalants most commonly abused
      by workers and young drug addicts. In this study, we examined the changes in
      sleep patterns and monoamine content induced by chronic toluene exposure. Rats
      were chronically exposed to toluene vapors beginning at 30 days of age for a
      duration of 30 days. Experiment I was performed in a control group (n=10) and a
      chronic toluene exposure group (n=10). Rats were implanted with bipolar stainless
      steel electrodes for electroencephalographic recording (EEG). In experiment II,
      conducted in two other groups (control and exposed to toluene, n=10 each),
      animals were sacrificed by decapitation prior to chromatographic analysis. We
      found that chronic toluene administration affected the organization of sleep
      patterns and monoamine content. Dopamine (DA) and noradrenaline (NA) increased in
      the midbrain and striatum. 3,4-dihydroxyphenylacetic acid (DOPAC) increased only
      in the striatum. Midbrain levels of serotonin (5-HT) increased in the pons and
      decreased in the hypothalamus and striatum. 5-hydroxyindoleacetic acid (5-HIAA)
      increased in the pons, midbrain and striatum and decreased in the hypothalamus.
      Chronic toluene exposure induced changes in the serotonergic and dopaminergic
      systems and increased SWS and PS deficits. We conclude that toluene exposure
      disrupts the sleep-wake cycle by affecting the monoaminergic response in cerebral
      areas related to sleep.

PMID- 21731074
TI  - Status epilepticus evokes prolonged increase in the expression of CCL3 and CCL4
      mRNA and protein in the rat brain.
AB  - CCL3 and CCL4 are proinflammatory chemokines belonging to the CC family. Increase
      in expression of mRNA coding for various chemokines including CCL3 and CCL4 has
      been often detected with global transcriptome profiling of brain tissue following
      epileptogenic stimuli as well as in epilepsy in experimental models and in human
      patients. Despite this, little is known about the expression of these proteins in
      epileptogenesis or epilepsy. In the present work CCL3 and CCL4 mRNA and protein
      expression were studied in the amygdala stimulation model of temporal lobe
      epilepsy using quantitiative PCR and immunohistochemistry. Expression of CCL3 and
      CCL4 mRNA in the block of tissue containing enthorinal and piriform cortices,
      amygdala and piriform nucleus was markedly up-regulated at 1, 4, 14 and 30 days
      following stimulation and in hippocampal CA1 was significantly increased at 1 and
      4 days following stimulation. Expression of CCL3 and CCL4 proteins was elevated
      in astrocytes in the enthorinal and piriform cortices, amygdala, and hippocampus
      showing the largest increase at 4D after status epilepticus. Increase in mRNA and
      protein levels of CCL3 and CCL4 in the animal model of temporal lobe epilepsy
      suggests their role in disease development or recovery form epileptogenic insult.
      Existence of multiple targets for these chemokines in the damaged brain allows
      several possibilities of influencing neuronal and glial functions.

PMID- 21731075
TI  - The interactions of nitric oxide and adenosine on penicillin-induced epileptiform
      activity in rats.
AB  - In this study, the influence of nitric oxide (NO) and adenosine systems on
      penicillin-induced epileptiform activity was examined in rats. NO donor, sodium
      nitroprusside (SNP, 50 micrograms per rat, i.c.v.) reduced the frequency but not
      the amplitude of epileptiform discharges. Non-selective NOS inhibitor, N-omega
      nitro-L-arginine methyl ester (L-NAME, 100 micrograms per rat, i.c.v.)
      practically did not exert any effect on the spike frequency and amplitude.
      Adenosine (100 micrograms per rat, i.c.) reduced spike frequency but not the
      amplitude, whereas theophylline (100 micrograms per rat, i.c.v.) increased the
      mean spike frequency and amplitude of penicillin-induced epileptiform discharges.
      Co-injection of theophylline and L-NAME did not cause a further increase in the
      epileptiform activity compared with theophylline. When NO production was blocked
      with L-NAME, the inhibitory effects of adenosine were lost. The obtained results
      suggest that NO and adenosine may decrease penicillin-induced epileptiform
      activity in rats and that NO, at least in part, may mediate the anticonvulsant
      effect of adenosine.

PMID- 21731076
TI  - Pilocarpine-induced status epilepticus alters hippocampal PKC expression in mice.
AB  - We investigated the protein expression of different protein kinase C (PKC)
      isoforms (PKC-alpha, PKC-beta1, PKC-beta2, PKC-gamma, PKC-delta, PKC-epsilon, PKC
      eta and PKC-zeta) in the hippocampus of normal control mice and progressive
      changes in PKC isoforms expression during and after pilocarpine induced status
      epilepticus (PISE). We showed the reduced expression of PKC-delta, PKC-eta and
      PKC-zeta in interneurons in the CA1 area and in the hilus of the dentate gyrus
      during or after PISE. Increased expression of PKC-alpha and PKC-beta1 was
      demonstrated in the stratum pyramidale of CA3 area, and PKC-epsilon was up
      regulated in the stratum lucidum of the CA3 area during or after PISE. Our
      results suggest that hippocampal PKC isoforms may play different roles in seizure
      generation, and be targets for development of anti-convulsive drugs.

PMID- 21731077
TI  - Relief of carotid stenosis improves impaired cognition in a rat model of chronic
      cerebral hypoperfusion.
AB  - To investigate how cognitive impairment is affected by the relief of bilateral
      carotid stenosis, chronic cerebral hypoperfusion was established through stenosis
      of the bilateral carotid common artery in adult Sprague-Dawley rats.
      Subsequently, the model rats received the intragastric placebo, donepezil (5 mg
      per kg), or surgery to relieve carotid stenosis after bilateral carotid common
      artery stenosis. After carotid stenosis was relieved, the cerebral blood flow
      values significantly increased, and P300 latency and escape latency in the Morris
      water-maze were significantly shortened. The concentrations of acetylcholine and
      norepinephrine in the dorsal hippocampus increased after carotid stenosis was
      relieved. Furthermore, P300 latency and escape latency were shortened in the
      relief-treated group compared to the drug-treated group, and acetylcholine levels
      in the relief-treated group were higher than the drug-treated group. No
      significant difference was found for the norepinephrine levels in the dorsal
      hippocampus between the relief-treated and drug-treated groups. Cognitive
      impairment can be significantly reduced by bilateral carotid stenosis relief, and
      the effect of relieving stenosis on cognitive dysfunction is superior to the
      effect of administering an acetylcholinesterase inhibitor.

PMID- 21731078
TI  - One- and three-time mild hypobaric hypoxia modifies expression of mitochondrial
      thioredoxin-2 in hippocampus of rat.
AB  - Our previous study demonstrated that preconditioning by 3-times repetitive mild
      hypoxia significantly augmented expression of mitochondrial thioredoxin-2 (Trx-2)
      at 3 h after subsequent acute severe hypoxia in rat hippocampus. However, it was
      unclear whether this augmentation was due to build up of Trx-2 by mild hypoxia
      before severe hypoxia or by modification of reaction to severe hypoxia itself. To
      answer on this question we study the expression level during and after
      preconditioning without subsequent severe hypoxia. Trx-2 expression was studied
      by immunocytochemistry 3 h and 24 h after first session and 3 h and 24 h after
      last session of 3-times (spaced at 24 h) mild hypobaric hypoxia (360 Torr, 2h).
      At 3 h after 1-time hypoxia (first session of 3-time hypoxia) the total number of
      Trx-2-immunoreactive cells (Nt) was significantly decreased in contrast with
      control in CA2, CA3 and DG. The number of cells with intensive expression of Trx
      2 (Ni) was reduced in CA1 and CA3. At 24 h after the same 1-time hypoxia Nt was
      lower than in control and at 3 h time-point in all hippocampal areas studied
      (CA1, CA2, CA3 and DG); Ni was decreased only compared to control in CA1 and CA3.
      At 3 h after last session of 3-times hypoxia Nt and Ni were significantly down
      regulated in comparison with control only in CA1. At 24 h after it Nt was
      significantly decreased compared to control in CA1, CA2 and CA3 (in DG the
      decrease was not statistically significant) but in all areas was higher than at
      24 h after 1-time hypoxia. Dynamics of Nt changes from 3-hours after single to 24
      hours after triple moderate hypoxia had the wave phase character. These findings
      indicate that Trx-2 expression in most areas of hippocampus was decreased to 24 h
      after 3-time mild hypoxia. Thus the augmentation of Trx-2 expression in
      hippocampal neurons of preconditioned animals in response to subsequent severe
      hypoxia is caused obviously not by Trx-2 accumulation during preconditioning
      sessions but by modification of reaction to severe impact.

PMID- 21731079
TI  - Cellular neuropathology of absence epilepsy in the neocortex: a population of
      glial cells rather than neurons is impaired in genetic rat model.
AB  - It is well accepted that absence epilepsy is not accompanied by structural brain
      abnormalities. In the present report, we challenged this view based on
      microscopic analysis of neocortex in a genetic model of absence epilepsy, WAG/Rij
      rats. Density of neurons and glial cells was measured in the motor, somatosensory
      and cingular cortical areas in epileptic WAG/Rij rats and in non-epileptic
      control ACI rats. More extensive and significant differences between two strains
      were found in a population of glial cells and less significant - in neurons. In
      contract to ACI rats, WAG/Rij rats showed (1) a deficit of glial cells and a
      lower glia-neuron index in the somatosensory and cingulate areas (deep layers);
      (2) a reduced number of neurons locally in the motor cortex. The somatosensory
      cortex (deep layers) is known to play a key role in triggering of epileptic
      discharges, and an impairment of glia-neuron interactions in this area might
      underlie pathological processes in a primary epileptic focus. In the motor
      cortex, epileptiform activity is known to reach the highest amplitude, and this
      may cause or result from a deficit of neurons. Our data suggest the critical role
      of glial cells and glia-neuron interactions in pathogenesis of absence epilepsy.

PMID- 21731080
TI  - Neuropharmacological approach against MPTP (1-methyl-4-phenyl-1,2,3,6-
      tetrahydropyridine)-induced mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease that appears
      essentially as a sporadic condition. PD is well known to be a chronic and
      progressive neurodegenerative disease produced by a selective degeneration of
      dopaminergic neurons in the substantia nigra pars compacta. The main clinical
      features of PD include tremor, bradykinesia, rigidity and postural instability.
      Most insights into pathogenesis of PD come from investigations performed in
      experimental models of PD, especially those produced by neurotoxins. The
      biochemical and cellular alterations that occur after 1-methyl-4-phenyl-1,2,3,6-
      tetrahydropyridine (MPTP) treatment are remarkably similar to that observed in
      idiopathic PD. Furthermore, it is well known that acute treatment with MPTP can
      cause a severe loss of tyrosine hydroxylase and dopamine transporter protein
      levels and dopamine contents in the striatum of mice, as compared to continuous
      MPTP treatment. Thus these findings may support the validity of acute MPTP
      treatment model for unraveling in the neurodegenerative processes in PD. In this
      review, we discuss the neuroprotective effects of various compounds against
      neuronal cell loss in an MPTP model of PD. This review may lead to a much better
      understanding of PD as well as provide novel clues to new targets for therapeutic
      interventions in PD patients.

PMID- 21731081
TI  - Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this
      multiply cascade.
AB  - The pathophysiology of acute spinal cord injury (SCI) involves primary and
      secondary mechanisms of injury. Though both mechanisms are involved in the
      neurological dysfunction in SCI most research however has focused on
      understanding the pathophysiology of the secondary damage and reducing the amount
      of delayed cell loss following SCI. Research has revealed extensive therapeutic
      windows in secondary injury mechanisms that could be manipulated by appropriate
      exogenous interventions. In contrast, primary injury to the cord happens
      unexpectedly, and it is associated with inevitable delays; ranging from several
      hours to days before care intervention is administered. Therefore, apart from
      achieving patient's stabilization, the therapeutic window in the primary phase of
      injury is essentially obliterated, and consequently inaccessible for specialized.
      Coupled to this, the exacerbating effect of secondary injury mechanisms has
      generally commenced before the specialist intervention. Hence, knowledge of
      secondary injury mechanisms and their intricacies are invaluable requisite for
      any tailored therapeutic strategy in the persistent search for a cure of SCI.
      There are about 25 well-established secondary injury mechanisms in SCI, and are
      found in bits or clusters in literature. A vast number of these articles are not
      open access. Besides, articles with a comprehensive catalog of these mechanisms
      are not readily available. This article has cataloged over twenty five identified
      secondary mechanisms of injury in the spinal cord in an open access portal, and
      is particularly versatile for starters in spinal cord injury research.

PMID- 21731082
TI  - NEIGHBORHOOD IMMIGRATION AND NATIVE OUT-MIGRATION.
AB  - This study combines data from the Panel Study of Income Dynamics with data from
      four censuses to examine the effects of foreign-born populations in the immediate
      neighborhood of residence and surrounding neighborhoods on the residential
      mobility decisions of native-born black and white householders. We find that the
      likelihood of out-mobility for native householders is significantly and
      positively associated with the relative size of, and increases in, the immigrant
      population in the neighborhood. Consistent with theoretical arguments related to
      the distance dependence of mobility, large concentrations of immigrants in
      surrounding areas reduce native out-mobility, presumably by reducing the
      attractiveness of the most likely mobility destinations. A sizable share of local
      immigration effects can be explained by the mobility-related characteristics of
      native-born individuals living in immigrant-populated areas, but the racial
      composition of the neighborhood (for native whites) and local housing market
      conditions (for native blacks) also are important mediating factors. The
      implications of these patterns for processes of neighborhood change and broader
      patterns of residential segregation are discussed.

PMID- 21731083
TI  - Microbial Communities as Experimental Units.
AB  - Artificial ecosystem selection is an experimental technique that treats microbial
      communities as though they were discrete units by applying selection on community
      level properties. Highly diverse microbial communities associated with humans and
      other organisms can have significant impacts on the health of the host. It is
      difficult to find correlations between microbial community composition and
      community-associated diseases, in part because it may be impossible to define a
      universal and robust species concept for microbes. Microbial communities are
      composed of potentially thousands of unique populations that evolved in intimate
      contact, so it is appropriate in many situations to view the community as the
      unit of analysis. This perspective is supported by recent discoveries using
      metagenomics and pangenomics. Artificial ecosystem selection experiments can be
      costly, but they bring the logical rigor of biological model systems to the
      emerging field of microbial community analysis.

PMID- 21731084
TI  - Advanced dental local nerve block anesthesia - a comment.

PMID- 21731086
TI  - Why CVMA membership? - a comment.

PMID- 21731088
TI  - Our profession 2011.

PMID- 21731089
TI  - Veterinary medical ethics: an ethicist's commentary on unintended consequences of
      a "downer animal" law.

PMID- 21731090
TI  - Dermatophytosis due to Microsporum persicolor: a retrospective study of 16 cases.
AB  - A retrospective study of 16 cases of dermatophytosis due to Microsporum
      persicolor in dogs is reported. Hunting dogs were overrepresented (12/16). Skin
      lesions were observed on the face in all cases, but also on other locations
      (limbs, neck). The lesions included alopecia (15/16), erythema (13/16), scales
      (14/16), and crusts (13/16). Histopathology was performed in 10 cases and showed
      folliculitis and a lichenoid interface dermatitis. Fungal culture was positive in
      all cases and clinical resolution was achieved with standard antifungal agents
      (enilconazole, ketoconazole, griseofulvin). Two recurrences were observed (new
      contacts with rodents).

PMID- 21731091
TI  - Acute erythroid leukemia with multilineage dysplasia in a cat.
AB  - Dysplastic features of erythroid and megakaryocytic lineages were observed in a
      cat with acute erythroid leukemia. We demonstrated that flow cytometry analysis
      of the expression of glycophorin A and CD71 by neoplastic cells can be helpful in
      the diagnosis of this type of feline leukemia.

PMID- 21731092
TI  - Unusual central nervous system lesions in slaughter-weight pigs with porcine
      circovirus type 2 systemic infection.
AB  - Porcine circovirus type 2 systemic infection was diagnosed in 2 slaughter-weight
      pigs based on postmortem examination. The infection was associated with unusual
      central nervous system lesions characterized by a multifocal lymphohistiocytic to
      granulomatous meningoencephalomyelitis with giant cell formation. The role of
      these nervous system lesions in the development of the clinical signs in these
      pigs remains uncertain.

PMID- 21731093
TI  - Optic neuritis caused by canine distemper virus in a Jack Russell terrier.
AB  - An atypical case of canine distemper (CD) was diagnosed in a vaccinated healthy
      adult dog. The patient was presented circling, seizuring, and blind. Postmortem
      examination resulted in a diagnosis of CD. Optic neuritis was diagnosed, a
      finding not previously described in the context of CD virus infection presenting
      solely with neurological signs.

PMID- 21731094
TI  - Comparison between auricular and standard rectal thermometers for the measurement
      of body temperature in dogs.
AB  - Although the rectal mucosa remains the traditional site for measuring body
      temperature in dogs, an increasing number of clinicians have been using auricular
      temperature to estimate core body temperature. In this study, 88 mature healthy
      dogs had body temperatures measured with auricular and rectal thermometers. The
      mean temperature and confidence intervals were similar for each method, but Bland
      Altman plots showed high biases and limits of agreement unacceptable for clinical
      purposes. The results indicate that auricular and rectal temperatures should not
      be interpreted interchangeably.

PMID- 21731095
TI  - Validating the assessment of bull sperm morphology by veterinary practitioners.
AB  - The objective of this study was to validate the assessment of bull sperm
      morphology done by veterinary practitioners. Out of 1606 bulls, 1400 (87.2%) and
      1344 (83.7%) were designated by practitioners and an experienced andrologist,
      respectively, as having > 70% morphologically normal sperm. In 92% of the
      evaluations, there was agreement between the designations chosen.

PMID- 21731096
TI  - Disseminated hemangiosarcoma in a cow.
AB  - An antemortem diagnosis of disseminated hemangiosarcoma with extensive hepatic
      and splenic involvement was made in a 9-year-old cow evaluated for lethargy,
      weight loss, regenerative anemia, thrombocytopenia, and elevated liver enzymes.
      This is the first report of hemangiosarcoma in a cow with a suspected primary
      location of the liver and/or spleen.

PMID- 21731097
TI  - A survey of the fecal bacteria of bison (Bison bison) for potential pathogens and
      antimicrobial susceptibility of bison-origin E. coli.
AB  - An observational study determined the normal fecal bacterial flora of clinically
      healthy bison, detected the presence of common potential zoonotic pathogens, and
      determined the antimicrobial susceptibility of isolated E. coli strains. Ninety
      six fecal samples from 10 captive herds were cultured for aerobic, anaerobic,
      facultative, and microaerophillic bacteria. Nineteen major genera of gram
      positive and 8 genera of gram-negative bacteria were identified. Salmonella spp.
      were not detected but some of the isolated bacteria are potential
      gastrointestinal pathogens. Minimum inhibitory concentrations (MIC) of 24
      antimicrobials were determined for the E. coli isolated. Nearly all were
      susceptible to 23 of the 24 antimicrobials but there was a reduced susceptibility
      to sulphonamide. There were fewer resistant strains than were reported in recent
      studies of generic E. coli from cattle living in the same area.

PMID- 21731098
TI  - Chronic intestinal pseudo-obstruction in a horse: a case of myenteric
      ganglionitis.
AB  - An 11-year-old Quarter horse mare was presented for recurrent episodes of colic.
      A chronic intestinal pseudo-obstruction was diagnosed. Medical treatment and
      surgical resection of the colon were performed but the condition did not improve
      and the horse was euthanized. Histopathological examination revealed a myenteric
      ganglionitis of the small intestine and ascending colon.

PMID- 21731099
TI  - Premature lactation and retention of a mummified fetus with live birth of the co
      twin in a primiparous Morgan mare.
AB  - This report describes a primiparous 8-year-old Morgan mare, which displayed
      premature lactation that began at approximately 240 d of gestation and lasted
      approximately 4 wk. The premature lactation resolved spontaneously, and the
      pregnancy was subsequently carried to full term with the delivery of a live foal
      and a mummified fetus.

PMID- 21731100
TI  - Role of beta-hydroxybutyric acid in diabetic ketoacidosis: a review.
AB  - Diabetic ketoacidosis (DKA), a complication of diabetes mellitus, is a severe
      metabolic disease that often requires intensive treatment. Diagnosis of ketosis
      associated with DKA can be difficult due to variability in the metabolic state of
      DKA patients. Recognition of the clinical signs and definitive diagnosis are
      essential for proper treatment. This article reviews the formation of ketoacids
      during DKA and the role of beta-hydroxybutyric acid in the diagnosis and
      monitoring of DKA.

PMID- 21731101
TI  - Hypertrophic osteodystrophy preceding canine juvenile cellulitis in an Australian
      shepherd puppy.
AB  - A 10-week-old intact female Australian shepherd dog was presented sternally
      recumbent, mildly pyrexic, and painful on long bone palpation of both forelimbs.
      Based on radiographs she was diagnosed with hypertrophic osteodystrophy.
      Analgesia was provided with intravenous, oral, and topical medications.
      Approximately 2 wk later she was presented for facial swelling, regional
      dermatitis, and lymphadenopathy. Canine juvenile cellulitis was diagnosed and
      successfully treated.

PMID- 21731102
TI  - The one-size-fits-all dilemma.

PMID- 21731103
TI  - The VOHC seal - why is it important?

PMID- 21731104
TI  - Checklist for hiring a great locum.

PMID- 21731105
TI  - Regioselectivity of Catechol O-Methyltransferase Confers Enhancement of Catalytic
      Activity.
AB  - Catechol O-methyltransferase (COMT) metabolizes catechol moieties by methylating
      a single hydroxyl group at the meta- or para- hydroxyl position. Hydrophobic
      amino acids near the active site of COMT influence the regioselectivity of this
      reaction. Our sequence analysis highlights their importance by showing that these
      residues are highly conserved throughout evolution. Reaction barriers calculated
      in the gas phase reveal a lower barrier during methylation at the meta- position,
      suggesting that the observed meta-regioselectivity of COMT can be attributed to
      the substrate itself, and that COMT has evolved residues to orient the substrate
      in a manner that increases the rate of catalysis.

PMID- 21731106
TI  - Scaling Fiber Lasers to Large Mode Area: An Investigation of Passive Mode-Locking
      Using a Multi-Mode Fiber.
AB  - The mode-locking of dissipative soliton fiber lasers using large mode area fiber
      supporting multiple transverse modes is studied experimentally and theoretically.
      The averaged mode-locking dynamics in a multi-mode fiber are studied using a
      distributed model. The co-propagation of multiple transverse modes is governed by
      a system of coupled Ginzburg-Landau equations. Simulations show that stable and
      robust mode-locked pulses can be produced. However, the mode-locking can be
      destabilized by excessive higher-order mode content. Experiments using large core
      step-index fiber, photonic crystal fiber, and chirally-coupled core fiber show
      that mode-locking can be significantly disturbed in the presence of higher-order
      modes, resulting in lower maximum single-pulse energies. In practice, spatial
      mode content must be carefully controlled to achieve full pulse energy scaling.
      This paper demonstrates that mode-locking performance is very sensitive to the
      presence of multiple waveguide modes when compared to systems such as amplifiers
      and continuous-wave lasers.

PMID- 21731107
TI  - Evaluation of Respiratory Motion Effect on Defect Detection in Myocardial
      Perfusion SPECT: A Simulation Study.
AB  - The objective of this study is to investigate the effects of respiratory motion
      (RM) on defect detection in Tc-99m sestamibi myocardial perfusion SPECT (MPS)
      using a phantom population that includes patient variability. Three RM patterns
      are included, namely breath-hold, slightly enhanced normal breathing, and deep
      breathing. For each RM pattern, six 4-D NCAT phantoms were generated, each with
      anatomical variations. Anterior, lateral and inferior myocardial defects with
      different sizes and contrasts were inserted. Noise-free SPECT projections were
      simulated using an analytical projector. Poisson noise was then added to generate
      noisy realizations. The projection data were reconstructed using the OS-EM
      algorithm with 1 and 4 subsets/iteration and at 1, 2, 3, 5, 7, and 10 iterations.
      Short-axis images centered at the centroid of the myocardial defect were
      extracted, and the channelized Hotelling observer (CHO) was applied for the
      detection of the defect. The CHO results show that the value of the area under
      the receiver operating characteristics (ROC) curve (AUC) is affected by the RM
      amplitude. For all the defect sizes and contrasts studied, the highest or optimal
      AUC values indicate maximum detectability decrease with the increase of the RM
      amplitude. With no respiration, the ranking of the optimal AUC value in
      decreasing order is anterior then lateral, and finally inferior defects. The AUC
      value of the lateral defect drops more severely as the RM amplitude increases
      compared to other defect locations. Furthermore, as the RM amplitude increases,
      the AUC values of the smaller defects drop more quickly than the larger ones. We
      demonstrated that RM affects defect detectability of MPS imaging. The results
      indicate that developments of optimal data acquisition methods and RM correction
      methods are needed to improve the defect detectability in MPS.

PMID- 21731108
TI  - Depth-of-Interaction Compensation Using a Focused-Cut Scintillator for a Pinhole
      Gamma Camera.
AB  - Preclinical SPECT offers a powerful means to understand the molecular pathways of
      drug interactions in animal models by discovering and testing new pharmaceuticals
      and therapies for potential clinical applications. A combination of high spatial
      resolution and sensitivity are required in order to map radiotracer uptake within
      small animals. Pinhole collimators have been investigated, as they offer high
      resolution by means of image magnification. One of the limitations of pinhole
      geometries is that increased magnification causes some rays to travel through the
      detection scintillator at steep angles, introducing parallax errors due to
      variable depth-of-interaction in scintillator material, especially towards the
      edges of the detector field of view. These parallax errors ultimately limit the
      resolution of pinhole preclinical SPECT systems, especially for higher energy
      isotopes that can easily penetrate through millimeters of scintillator material.
      A pixellated, focused-cut (FC) scintillator, with its pixels laser-cut so that
      they are collinear with incoming rays, can potentially compensate for these
      parallax errors and thus improve the system resolution. We performed the first
      experimental evaluation of a newly developed focused-cut scintillator. We scanned
      a Tc-99m source across the field of view of pinhole gamma camera with a
      continuous scintillator, a conventional "straight-cut" (SC) pixellated
      scintillator, and a focused-cut scintillator, each coupled to an electron
      multiplying charge coupled device (EMCCD) detector by a fiber-optic taper, and
      compared the measured full-width half-maximum (FWHM) values. We show that the
      FWHMs of the focused-cut scintillator projections are comparable to the FWHMs of
      the thinner SC scintillator, indicating the effectiveness of the focused-cut
      scintillator in compensating parallax errors.

PMID- 21731109
TI  - Comparison of Structurally-Related Alkoxide, Amine, and Thiolate-Ligated M (M=
      Fe, Co) Complexes: the Influence of Thiolates on the Properties of Biologically
      Relevant Metal Complexes.
AB  - Mechanistic pathways of metalloenzymes are controlled by the metal ion's
      electronic and magnetic properties, which are tuned by the coordinated ligands.
      The functional advantage gained by incorporating cysteinates into the active site
      of non-heme iron enzymes such as superoxide reductase (SOR) is not entirely
      understood. Herein we compare the structural and redox properties of a series of
      structurally-related thiolate, alkoxide, and amine-ligated Fe(II) complexes in
      order to determine how the thiolate influences properties critical to function.
      Thiolates are shown to reduce metal ion Lewis acidity relative to alkoxides and
      amines, and have a strong trans influence thereby helping to maintain an open
      coordination site. Comparison of the redox potentials of the structurally
      analogous compounds described herein indicates that alkoxide ligands favor the
      higher-valent Fe(3+) oxidation state, amine ligands favor the reduced Fe(2+)
      oxidation state, and thiolates fall somewhere in between. These properties
      provide a functional advantange for substrate reducing enzymes in that they
      provide a site at the metal ion for substrate to bind, and a moderate potential
      that facilitates both substrate reduction, and regeneration of the catalytically
      active reduced state. Redox potentials for structurally-related Co(II) complexes
      are shown to be cathodically-shifted relative to their Fe(II) analogues, making
      them ineffective reducing agents for substrates such as superoxide.

PMID- 21731110
TI  - Assessing the effect of the time since transition to organic farming on plants
      and butterflies.
AB  - 1.Environmental changes may not always result in rapid changes in species
      distributions, abundances or diversity. In order to estimate the effects of, for
      example, land-use changes caused by agri-environment schemes (AES) on
      biodiversity and ecosystem services, information on the time-lag between the
      application of the scheme and the responses of organisms is essential.2.We
      examined the effects of time since transition (TST) to organic farming on plant
      species richness and butterfly species richness and abundance. Surveys were
      conducted in cereal fields and adjacent field margins on 60 farms, 20
      conventional and 40 organic, in two regions in Sweden. The organic farms were
      transferred from conventional management between 1 and 25 years before the survey
      took place. The farms were selected along a gradient of landscape complexity,
      indicated by the proportion of arable land, so that farms with similar TST were
      represented in all landscape types. Organism responses were assessed using model
      averaging.3.Plant and butterfly species richness was c.20% higher on organic
      farms and butterfly abundance was about 60% higher, compared with conventional
      farms. Time since transition affected butterfly abundance gradually over the 25
      year period, resulting in a 100% increase. In contrast, no TST effect on plant or
      butterfly species richness was found, indicating that the main effect took place
      immediately after the transition to organic farming.4.Increasing landscape
      complexity had a positive effect on butterfly species richness, but not on
      butterfly abundance or plant species richness. There was no indication that the
      speed of response to organic farming was affected by landscape
      complexity.5.Synthesis and applications. The effect of organic farming on
      diversity was rapid for plant and butterfly species richness, whereas butterfly
      abundance increased gradually with time since transition. If time-lags in
      responses to AESs turn out to be common, long-term effects would need to be
      included in management recommendations and policy to capture the full potential
      of such schemes.

PMID- 21731111
TI  - The Modulation of Operant Variation by the Probability, Magnitude, and Delay of
      Reinforcement.
AB  - Recent studies have demonstrated that the expectation of reward delivery has an
      inverse relationship with operant behavioral variation (e.g., Stahlman, Roberts,
      & Blaisdell, 2010). Research thus far has largely focused on one aspect of
      reinforcement - the likelihood of food delivery. In two experiments with pigeons,
      we examined the effect of two other aspects of reinforcement: the magnitude of
      the reward and the temporal delay between the operant response and outcome
      delivery. In the first experiment, we found that a large reward magnitude
      resulted in reduced spatiotemporal variation in pigeons' pecking behavior. In the
      second experiment, we found that a 4-s delay between response-dependent trial
      termination and reward delivery increased variation in behavior. These results
      indicate that multiple dimensions of the reinforcer modulate operant response
      variation.

PMID- 21731112
TI  - Thermally-Polymerized Rylene Nanoparticles.
AB  - Rylene dyes functionalized with varying numbers of phenyl trifluorovinylether
      (TFVE) moieties were subjected to a thermal emulsion polymerization to yield
      shape-persistent, water-soluble chromophore nanoparticles. Perylene and terrylene
      diimide derivatives containing either two or four phenyl TFVE functional groups
      were synthesized and subjected to thermal emulsion polymerization in tetraglyme.
      Dynamic light scattering measurements indicated that particles with sizes ranging
      from 70 - 100 nm were obtained in tetraglyme, depending on monomer concentration.
      The photophysical properties of individual monomers were preserved in the
      nanoemulsions and emission colors could be tuned between yellow, orange, red, and
      deep red. The nanoparticles were found to retain their shape upon dissolution
      into water and the resulting water suspensions displayed moderate to high
      fluorescence quantum yield.

PMID- 21731113
TI  - "Are You an African?" The Politics of Self-Construction in Status-Based Social
      Movements.
AB  - Current debates over identity politics hinge on the question of whether status
      based social movements encourage parochialism and self-interest or create
      possibilities for mutual recognition across lines of difference. Our article
      explores this question through comparative, ethnographic study of two racially
      progressive social movements, "pro-black" abolitionism and "conscious" hip hop.
      We argue that status-based social movements not only enable collective identity,
      but also the personal identities or selves of their participants. Beliefs about
      the self create openings and obstacles to mutual recognition and progressive
      social action. Our analysis centers on the challenges that an influx of
      progressive, anti-racist whites posed to each movement. We examine first how each
      movement configured movement participation and racial identity and then how
      whites crafted strategic narratives of the self to account for their
      participation in a status-based movement they were not directly implicated in. We
      conclude with an analysis of the implications of these narratives for a critical
      politics of recognition. Keywords: identity politics, social movements, race,
      self, hip hop.

PMID- 21731114
TI  - Probing the Electronic Demands of Transmetalation in the Palladium-Catalyzed
      Cross-Coupling of Arylsilanolates.
AB  - The electronic characteristics of coupling partners in the transmetalation step
      for the cross-coupling reaction of arylsilanolates have been investigated. The
      ability to interrogate the transmetalation event by in situ preparation of the
      arylpalladium(II) silanolate intermediate has enabled a Hammett analysis for both
      the aryl electrophile and arylsilanolate to be conducted. These studies reveal
      that electron-donating groups on the silicon nucleophile and electron-withdrawing
      groups on the electrophile accelerate the transmetalation process.

PMID- 21731115
TI  - Microwave-assisted multicomponent reaction in water leading to highly
      regioselective formation of benzo[f]azulen-1-ones.
AB  - Microwave-assisted three-component reaction has been established for the
      regioselective synthesis of benzo[f]azulen-1-ones. The reaction was performed in
      aqueous media under microwave irradiation by using readily available and
      inexpensive starting materials. A total of 38 examples were examined to show a
      broad substrate scope and good overall yields (70-89%). The present new synthesis
      shows attractive green chemistry characteristics, such as the use of water as
      reaction media, concise one-pot conditions, short reaction periods (7-24 min),
      easy work-up/purification and reduced waste production without the use of any
      strong acids or metal promoters.

PMID- 21731116
TI  - Heterocycles via intramolecular platinum-catalyzed propargylic substitution.
AB  - We report a Pt(II)-catalyzed cyclization of nucleophile-tethered propargylic
      acetates yielding substituted heterocycles containing multiple heteroatoms
      including morpholines, dioxanes and sulfamates with high cis-selectivity.

PMID- 21731117
TI  - A new approach to fused furan ring systems and benzofurans: Intramolecular
      cyclization reactions of unsaturated acyloxy sulfone derivatives.
AB  - Unsaturated acyloxy sulfones 3 undergo intramolecular cyclization upon
      deprotonation with LHMDS in THF. Dehydration and double bond isomerization of the
      products upon exposure to acid, gave the fused ring furans, 4, in good yields.
      This strategy could be readily adapted to 12 from the cyclization reactions of
      acyloxy sulfones 11 prepared from phenols. Finally, this approach could be
      successfully modified to access dihydropyrans and benzopyrans.

PMID- 21731118
TI  - Post-fire primary production and plant community dynamics in chaparral stands
      exposed to varying levels of nitrogen deposition.
AB  - High levels of atmospheric nitrogen (N) deposition to southern California
      chaparral shrublands may interact with fire to affect biomass production and
      plant species composition during secondary succession. To determine the potential
      interactions between post fire recovery and N deposition we compared rates of
      aboveground net primary production (ANPP), shrub growth, and the relative
      abundance of Adenostoma fasciculatum, other sub-dominant shrubs, and herbaceous
      species of three chaparral stands exposed to different levels of atmospheric N
      deposition over the first 3 years of post-fire succession. Our data suggest that
      rates of ANPP (gdw m(-2) month(-1)) and aboveground N storage (gN m(-2) month(
      1)) for these chaparral stands were not related to N deposition even though sites
      exposed to high levels of N deposition had significantly higher rates of shrub
      growth (gdw plant(-1) month(-1)) and N uptake (gN plant(-1) month(-1)). However,
      high-N stands were composed of larger shrubs with a lower density, and this trade
      off between shrub size and density may explain the low correlation between N
      deposition and post-fire ANPP. Differences in relative plant species abundance
      between sites were significantly correlated with N deposition exposure, where
      stands exposed to high N deposition had a lower relative abundance of A.
      fasciculatum and a higher relative abundance of other shrub and herbaceous
      species. While many factors can affect rates and patterns of post-fire recovery,
      these results suggest that chronic exposure to N deposition may significantly
      alter plant growth and species composition in successional chaparral stands.

PMID- 21731119
TI  - Correlates of Externalizing Behavior Symptoms Among Youth Within Two
      Impoverished, Urban Communities.
AB  - The current study examines whether risk factors associated with child
      externalizing behavior symptoms differ between two similar low-income urban
      communities, using baseline parent data of 154 African American youth (ages 9-15)
      participating in the Collaborative HIV-Prevention and Adolescent Mental Health
      Project (CHAMP) family program. Separate multiple regression analyses of each
      city sample indicated that greater child externalizing symptoms were associated
      with increasing parenting hassles for New York families (n = 46), but greater
      parent mental health symptoms for participants in Chicago (n = 108).
      Understanding such distinctions between communities is an important first step
      towards tailoring services to unique community needs.

PMID- 21731120
TI  - The Undoing Effect of Positive Emotions.
AB  - Positive emotions are hypothesized to undo the cardiovascular aftereffects of
      negative emotions. Study 1 tests this undoing effect. Participants (n = 170)
      experiencing anxiety-induced cardiovascular reactivity viewed a film that
      elicited (a) contentment, (b) amusement, (c) neutrality, or (d) sadness.
      Contentment-eliciting and amusing films produced faster cardiovascular recovery
      than neutral or sad films did. Participants in Study 2 (n = 185) viewed these
      same films following a neutral state. Results disconfirm the alternative
      explanation that the undoing effect reflects a simple replacement process.
      Findings are contextualized by Fredrickson's broaden-and-build theory of positive
      emotions (B. L. Fredrickson, 1998).

PMID- 21731121
TI  - Polyhexanide and hydrogen peroxide inhibit proteoglycan synthesis of human
      chondrocytes.
AB  - The use of local antiseptics is a common method in septic joint surgery. We
      tested polyhexanide and hydrogen peroxide, two of the most frequently used
      antiseptics with high efficacy and low toxicity. The purpose of this study was to
      evaluate the effects of both antiseptics on the extracellular cartilaginous
      matrix synthesis of human chondrocytes. Chondrocytes were isolated from donated
      human knee joints, embedded in alginate beads, and incubated for 10 and 30
      minutes with polyhexanide (0.04%), hydrogen peroxide (3%), or phosphate-buffered
      saline (PBS) for control. Cartilaginous matrix production was quantified through
      light microscopic analysis of Alcian blue staining. Cell number and morphology
      were detected by histological analysis. Chondrocytes showed a decreased intensity
      of blue colouring after antiseptic treatment versus PBS. In contrast to that,
      neither the cell number per view field nor the cell morphology differed between
      the groups. Polyhexanide has more toxic potential than hydrogen peroxide. Based
      on the fact that the cell number and morphology was not altered by the substances
      at the examined concentrations, the lower intensity of Alcian blue staining of
      treated chondrocytes indicates a decreased cartilage-specific matrix synthesis by
      polyhexanide more than by hydrogen peroxide and control.

PMID- 21731122
TI  - Family Types, Direct Money Transfers from Parents, and School Enrollment among
      Youths.
AB  - Intrafamily resource transfers have not been studied extensively as a process
      that may help reduce the well-being disadvantage of stepchildren in parental
      remarriages relative to biological children in parental first marriages. The
      process is examined here by analyzing the link between direct parental money
      transfers and academic outcomes, as measured by enrollment. I develop and test
      two alternative hypotheses pertaining to a part of this link, which distinctly
      applies to children of remarried stepfamilies--the component not shared with
      children in intact families. An adaptive strategy hypothesis posits a well-being
      enhancing distinct component, operationalized as a positive interaction effect
      between measures of parental transfers * stepchildren in parental remarriages. A
      compromised use hypothesis posits a well-being compromising one, implying a
      negative interaction effect. Two sets of results from analyzing data on 18-21
      year olds over multiple years (Nyouth-age=5,736, Nperson=3,615) in the first five
      waves of the National Longitudinal Survey of Youth 1997 (NLSY97) support the
      adaptive strategy hypothesis: a) the interaction effect (income received from
      parents * being a stepchild in a parental remarriage) has a positive sign; and b)
      this interaction effect is consistently positive, whether the youth is at risk of
      attending high school or college, even when the direction of the shared component
      of the link, as measured by the main effect of income from parents, varies by the
      level of schooling. The results suggest the presence of a robust well-being
      enhancing money transfer mechanism supporting children in some remarried
      stepparent families.

PMID- 21731123
TI  - Effects of CPAP on daytime function.

PMID- 21731126
TI  - The need for pharmacovigilance in sleep medicine.

PMID- 21731127
TI  - Draining the homeostat.

PMID- 21731128
TI  - Introduction to forum on critical topics in SLEEP.

PMID- 21731129
TI  - What is the meaning of the ATP surge during sleep?

PMID- 21731130
TI  - Does the brain gain back energy during sleep? But what does it mean?

PMID- 21731131
TI  - Measuring in vivo metabolite levels in brain.

PMID- 21731132
TI  - Repeatability is not the same as accuracy.

PMID- 21731133
TI  - Replies to commentaries on ATP changes during sleep.

PMID- 21731134
TI  - Sleep neurobiology from a clinical perspective.
AB  - Many neurochemical systems interact to generate wakefulness and sleep.
      Wakefulness is promoted by neurons in the pons, midbrain, and posterior
      hypothalamus that produce acetylcholine, norepinephrine, dopamine, serotonin,
      histamine, and orexin/hypocretin. Most of these ascending arousal systems
      diffusely activate the cortex and other forebrain targets. NREM sleep is mainly
      driven by neurons in the preoptic area that inhibit the ascending arousal
      systems, while REM sleep is regulated primarily by neurons in the pons, with
      additional influence arising in the hypothalamus. Mutual inhibition between these
      wake- and sleep-regulating regions likely helps generate full wakefulness and
      sleep with rapid transitions between states. This up-to-date review of these
      systems should allow clinicians and researchers to better understand the effects
      of drugs, lesions, and neurologic disease on sleep and wakefulness.

PMID- 21731135
TI  - Prevalence and polysomnographic correlates of insomnia comorbid with medical
      disorders.
AB  - STUDY OBJECTIVES: To determine the prevalence and polysomnographic correlates of
      insomnia in subjects with self-reported medical disorders. DESIGN: Prospective
      cross-sectional study. PARTICIPANTS: Community-based sample of 3282 men and women
      aged 18 to 65 years old, with a subset who underwent polysomnography.
      MEASUREMENTS: Self-reported measures of sleep habits and current health, and
      polysomnographic sleep variables. RESULTS: The prevalence of insomnia was 21.4%.
      The adjusted odds of insomnia were 2.2 times as high in persons with any medical
      disorders as in those without medical disorders. Specifically, odds of insomnia
      were higher in people with heart disease (OR = 1.6 [95% CI: 1.2-23], P = 0.004),
      hypertension (1.5 [12-18], P < 0.001), diabetes (1.4 [105-20], P = 0.04), stomach
      ulcers (2.1 [1.6-2.7], P < 0.001), arthritis (1.8 [1.5-2.2], P < 0.001), migraine
      (1.8 [1.5-2.1], P < 0.001), asthma (1.6 [1.3-2.0], P = 0.04), COPD (1.9 [1.5
      2.5], P < 0.001), neurological problems (2.0 [1.5-2.7], P < 0.001), and menstrual
      problems (1.7 [1.3-2.1], P < 0.001) than in people without these disorders.
      Prevalence of insomnia increased with increasing number of medical disorders.
      However, polysomnographic sleep was not significantly different in persons with
      or without medical disorders for most disorders assessed. CONCLUSION: This large
      population-based study suggests that insomnia is highly prevalent in diverse
      chronic medical disorders. However, polysomnographic evidence of disturbed sleep
      is present in only a subset of comorbid insomnia populations.

PMID- 21731136
TI  - Sedative medication use: prevalence, risk factors, and associations with body
      mass index using population-level data.
AB  - STUDY OBJECTIVES: To estimate the prevalence of and identify sociodemographic
      risk factors for sedative medication use in the general Canadian population, and
      to examine the association between sedative medication use and body mass index
      (BMI). DESIGN: Cross-sectional study SETTING: Canadian population PARTICIPANTS:
      Participants from the 1994-2003 Canadian national health surveys, the National
      Population Health Survey (NPHS) and the Canadian Community Health Survey (CCHS).
      For the 2003 CCHS, n = 134,072, ages 12-80+ years. INTERVENTIONS: Not applicable
      MEASUREMENTS AND RESULTS: The overall prevalence of sedative medication use in
      Canada in 2003 was 5.5%, having more than doubled since 1994. Notable rises in
      sedative medication use have occurred among men, non-elderly, and obese
      individuals. After adjusting for potential sociodemographic and health status
      confounders, including psychiatric comorbidities, the odds of sedative use were
      significantly greater among morbidly obese (BMI >= 35 kg/m(2)) men (OR = 1.89,
      95%CI = 1.02-3.53) and underweight (BMI < 18.5 kg/m(2)) women (OR = 2.11, 95%CI =
      1.26-3.53). CONCLUSIONS: The use of sedative medications has substantially risen
      among the general Canadian population, and among particular population subgroups.
      The greater odds of sedative medication use found among morbidly obese men may
      reflect the presence of underlying obstructive sleep apnea, which may in turn
      serve to explain in part the known relationship between sedative medications and
      mortality. The increase in sedative medications coupled with their known adverse
      health associations raises potential public health concerns.

PMID- 21731137
TI  - Prevalence and persistence of sleep disordered breathing symptoms in young
      children: a 6-year population-based cohort study.
AB  - STUDY OBJECTIVES: To describe the prevalence, persistence, and characteristics
      associated with sleep disordered breathing (SDB) symptoms in a population-based
      cohort followed from 6 months to 6.75 years. DESIGN: Avon Longitudinal Study of
      Parents and Children (ALSPAC). SETTING: England, 1991-1999. PARTICIPANTS: 12,447
      children in ALSPAC with parental report of apnea, snoring, or mouth-breathing
      frequency on any one of 7 questionnaires. MEASUREMENTS: Symptom prevalence rates
      assessed as "Always" and "Habitually"-are reported at 0.5, 1.5, 2.5, 3.5, 4.75,
      5.75, and 6.75 years of age. The proportion of children in whom symptoms develop,
      persist or abate between observation points is reported. Exploratory multivariate
      analyses identified SDB risk factors at 1.5, 4.75, and 6.75 years. RESULTS: The
      prevalence of apnea ("Always") is 1%-2% at all ages assessed. In contrast,
      snoring "Always" ranges from 3.6% to 7.7%, and snoring "Habitually" ranges from
      9.6% to 21.2%, with a notable increase from 1.5- 2.5 years. At 6 years old, 25%
      are habitual mouth-breathers. The "Always" and "Habitual" incidence of each
      symptom between time points is 1%-5% and 5%-10%, respectively. In multivariate
      analyses of combined symptoms, socioeconomic factors have stronger, more
      persistent effects upon increased SDB risk than gestational age, gender, or race
      (aside from 1.5 years); adenoidectomy decreases risk by 40%-50%. CONCLUSIONS:
      This is the first natural history study of the primary symptoms of SDB across a
      key 6-year period in the development of SDB symptoms. Snoring rates are higher
      and spike earlier than previously reported. Symptoms are dynamic, suggesting the
      need for early and continued vigilance in early childhood.

PMID- 21731138
TI  - Sleep duration and overweight in European children: is the association modified
      by geographic region?
AB  - STUDY OBJECTIVES: To investigate differences and a possible effect modification
      by geographical region in the association between sleep duration and overweight.
      DESIGN: Cross-sectional. SETTING: Primary schools and preschools in 8 European
      countries. PARTICIPANTS: 7867 children aged 2 to 9 years. INTERVENTIONS: Not
      applicable. MEASUREMENTS: Nocturnal sleep duration was assessed as part of a
      parental 24-h recall. Height and weight were measured by standardized procedures
      across centers. Data on personal, social, environmental and behavioral factors
      were collected using a standardized parental questionnaire. RESULTS: Sleep
      duration differed (P < 0.001) between European regions and normal vs. overweight
      children. A dose-dependent inverse association between sleep duration and
      overweight could be seen, with crude odds ratios ranging from 1.73 (99% CI 1.33;
      2.25) for sleeping between 10 and 11 h to 3.81 (99% CI 2.85; 5.09) for sleeping
      less than 9 h (reference category > 11 h). This persisted after adjustment, but
      remained significant only for sleeping less than 9 h per night (north: OR = 1.70;
      99% CI 1.13; 2.58 vs. south: OR = 2.84; 99% CI 1.57; 5.12) if stratified by
      region. No effect modification by region could be found, but adjustment for
      region accounted for changes in the effect estimate for sleeping less than 9 h
      (OR = 2.22; 99% CI 1.64; 3.02). The association was stronger in school children
      than in preschool children. CONCLUSION: Geographic region and related aspects
      even if they do not seem to modify the association between sleep and overweight
      should in any case be taken in consideration as a confounding factor on this
      association.

PMID- 21731139
TI  - Does sleep duration predict metabolic risk in obese adolescents attending
      tertiary services? A cross-sectional study.
AB  - STUDY OBJECTIVES: To determine, in a clinical sample of obese adolescents,
      whether shorter sleep duration is associated with metabolic risk and obesity
      severity. DESIGN: Cross-sectional study. SETTING: Tertiary care weight-management
      clinic in Cincinnati, OH, USA. PARTICIPANTS: 133 obese adolescents aged 10-16.9
      years. INTERVENTIONS: N/A. MEASUREMENTS: Multifaceted sleep duration data were
      examined with fasting venipuncture and anthropometric data collected during
      clinical care. PRIMARY OUTCOME: presence of metabolic syndrome. SECONDARY
      OUTCOMES: waist circumference, triglycerides, HDL-cholesterol, blood pressure,
      glucose, insulin resistance (HOMA-IR), and body mass index (BMI). PREDICTORS:
      Sleep duration by (1) parent-report, (2) self-report, and (3) multi-night
      actigraphy. ANALYSIS: Relationships between sleep duration and each outcome were
      examined via regression models, adjusted for potential confounders. RESULTS:
      Regardless of how measured, sleep duration showed no strong association with
      metabolic syndrome (OR 1.1 to 1.5, P = 0.2 to 0.8), BMI (beta -0.03 to -0.01, P =
      0.2 to 0.8), or most other outcomes. Lower triglycerides were predicted by
      shorter sleep duration by self-report (beta 12.3, P = 0.01) and actigraphy (beta
      13.6, P = 0.03), and shorter parent-reported sleep duration was associated with
      higher HDL-cholesterol (beta = -2.7, P = 0.002). CONCLUSIONS: Contrary to
      expectations, sleep duration was not associated with metabolic outcomes, and
      showed limited associations with lipid profiles. Although inadequate sleep may
      affect other areas of functioning, it appears premature to expect that
      lengthening sleep will improve BMI or metabolic outcomes in clinical samples of
      obese adolescents.

PMID- 21731140
TI  - Periodic limb movements and disrupted sleep in children with sickle cell disease.
AB  - STUDY OBJECTIVES: To describe the rate, distribution and correlates of periodic
      limb movements in sleep (PLMS) in children with sickle cell disease (SCD).
      DESIGN: Prospective, cross-sectional. SETTING: Hospital-based sleep laboratory.
      PARTICIPANTS: Sixty-four children aged 2-18 years with SCD, hemoglobin SS-type
      who had an overnight polysomnogram and a parent-completed Pediatric Sleep
      Questionnaire. Mean age was 8.4 years (SD 4.8); 50% were male. INTERVENTIONS:
      N/A. MEASUREMENTS AND RESULTS: The mean PLMS index was 3.7 (6.6) and ranged from
      0 to 31.8, with 23.4% of the sample having PLMS >= 5/h. Sleep efficiency was
      decreased (P = 0.03), and the total arousal index (P = 0.003) and PLMS arousal
      index (P < 0.001) were increased in children with PLMS >= 5/h compared to those
      with PLMS < 5/h. PLMS were most frequent in NREM stage 2 sleep and during the
      fourth hour of sleep. Inter-movement interval duration peaked at 25-30 s.
      "Growing pains worst in bed" or "restlessness of the legs", suggesting restless
      legs syndrome (RLS), were reported in 12.5% of the total sample and were more
      common in children with elevated PLMS. A PLMS score for identifying elevated PLMS
      in children, based on items from the Pediatric Sleep Questionnaire, did not
      significantly predict PLMS >= 5/h. CONCLUSIONS: Elevated PLMS are common in
      children with SCD and are associated with sleep disruption and symptoms of RLS.
      Future research into the time structure of PLMS, their causes and consequences,
      and development of a disease-specific sleep disorders screening questionnaire, is
      needed in children with SCD.

PMID- 21731141
TI  - Amelioration of obstructive sleep apnea in REM sleep behavior disorder:
      implications for the neuromuscular control of OSA.
AB  - OBJECTIVES: The relationship between REM sleep behavior disorder (RBD) and
      obstructive sleep apnea (OSA) remains unclear. We aimed to (1) explore the
      association of REM-related EMG activity (REMREEA) with OSA in RBD patients; (2)
      compare the severity of OSA between RBD patients with OSA (RBD-OSA) and their age
      , sex-, AHI-, and BMI- matched OSA controls. DESIGN: a. Correlation study in
      consecutive RBD subjects and b. case-control study SETTING: Sleep laboratory
      PARTICIPANTS: 71 RBD patients in the correlation study and 55 subjects (28 RBD
      OSA cases and 27 OSA controls) in the case-control study. INTERVENTION: N/A
      METHODS: Polysomnographic assessment to document the sleep architecture, sleep
      apnea related parameters, and REMREEA. RESULTS: (1) In the correlation study,
      increased REMREEA was associated with lower severity of OSA in RBD patients,
      including total AHI (r = -0.263), NREM AHI (r = -0.242), obstructive AHI (r = 
      0.265), and mean apnea duration (r = -0.353) (P < 0.05). (2) In the case-control
      study, RBD-OSA patients had lesser severity of sleep apnea parameters than OSA
      controls in terms of higher nadir SpO(2) (85.7% +/- 4.9% vs 80.8% +/- 5.9%, P <
      0.01), shorter maximum hypopnea duration (53.8 +/- 16.7 vs 69.4 +/- 22.4 seconds,
      P < 0.05), and maximum (45.8 +/- 20.5 vs 60.8 +/- 19.6 sec, P < 0.01) and mean
      apnea duration (22.3 +/- 8.1 vs 26.3 +/- 5.8 sec, P < 0.05). Significant
      interaction effects indicated that the usual REM sleep exacerbation of sleep
      apneas was seen only in OSA controls but not in RBD subjects. CONCLUSIONS: This
      study demonstrated that excessive EMG activity in RBD might protect patients
      against severe OSA and suggests this may be a naturalistic model for
      understanding neuromuscular control of OSA.

PMID- 21731142
TI  - The efficacy of a restart break for recycling with optimal performance depends
      critically on circadian timing.
AB  - OBJECTIVES: Under simulated shift-work conditions, we investigated the efficacy
      of a restart break for maintaining neurobehavioral functioning across consecutive
      duty cycles, as a function of the circadian timing of the duty periods. DESIGN:
      As part of a 14-day experiment, subjects underwent two cycles of five simulated
      daytime or nighttime duty days, separated by a 34-hour restart break. Cognitive
      functioning and high-fidelity driving simulator performance were tested 4 times
      per day during the two duty cycles. Lapses on a psychomotor vigilance test (PVT)
      served as the primary outcome variable. Selected sleep periods were recorded
      polysomnographically. SETTING: The experiment was conducted under standardized,
      controlled laboratory conditions with continuous monitoring. PARTICIPANTS: Twenty
      seven healthy adults (13 men, 14 women; aged 22-39 years) participated in the
      study. INTERVENTIONS: Subjects were randomly assigned to a nighttime duty
      (experimental) condition or a daytime duty (control) condition. The efficacy of
      the 34-hour restart break for maintaining neurobehavioral functioning from the
      pre-restart duty cycle to the post-restart duty cycle was compared between these
      two conditions. RESULTS: Relative to the daytime duty condition, the nighttime
      duty condition was associated with reduced amounts of sleep, whereas sleep
      latencies were shortened and slow-wave sleep appeared to be conserved.
      Neurobehavioral performance measures ranging from lapses of attention on the PVT
      to calculated fuel consumption on the driving simulators remained optimal across
      time of day in the daytime duty schedule, but degraded across time of night in
      the nighttime duty schedule. The 34-hour restart break was efficacious for
      maintaining PVT performance and other objective neurobehavioral functioning
      profiles from one duty cycle to the next in the daytime duty condition, but not
      in the nighttime duty condition. Subjective sleepiness did not reliably track
      objective neurobehavioral deficits. CONCLUSIONS: The 34-hour restart break was
      adequate for maintaining performance in the case of optimal circadian placement
      of sleep and duty periods (control condition) but was inadequate (and perhaps
      even detrimental) for maintaining performance in a simulated nighttime duty
      schedule (experimental condition). Current US transportation hours-of-service
      regulations mandate time off duty but do not consider the circadian aspects of
      shift scheduling. Reinforcing a recent trend of applying sleep science to inform
      policymaking for duty and rest times, our findings indicate that restart
      provisions in hours-of-service regulations could be improved by taking the
      circadian timing of the duty schedules into account.

PMID- 21731143
TI  - Sleep, wake and phase dependent changes in neurobehavioral function under forced
      desynchrony.
AB  - STUDY OBJECTIVES: The homeostatic-circadian regulation of neurobehavioral
      functioning is not well understood in that the role of sleep dose in relation to
      prior wake and circadian phase remains largely unexplored. The aim of the present
      study was to examine the neurobehavioral impact of sleep dose at different
      combinations of prior wake and circadian phase. DESIGN: A between-participant
      design involving 2 forced desynchrony protocols varying in sleep dose. Both
      protocols comprised 7 repetitions of a 28-h sleep/wake cycle. The sleep dose in a
      standard protocol was 9.33 h per 28-h day and 4.67 h in a sleep-restricted
      protocol. SETTING: A time-isolation laboratory at the Centre for Sleep Research,
      the University of South Australia. PARTICIPANTS: A total of 27 young healthy
      males participated in the study with 13 in the standard protocol (age 22.5 +/-
      2.2 y) and 14 in the sleep-restricted protocol (age 21.8 +/- 3.8 y).
      INTERVENTIONS: Wake periods during both protocols were approximately 4 h delayed
      each 28-h day relative to the circadian system, allowing performance testing at
      different combinations of prior wake and circadian phase. The manipulation in
      sleep dose between the 2 protocols, therefore, allowed the impact of sleep dose
      on neurobehavioral performance to be examined at various combinations of prior
      wake and circadian phase. MEASUREMENTS AND RESULTS: Neurobehavioral function was
      assessed using the psychomotor vigilance task (PVT). There was a sleep dose *
      circadian phase interaction effect on PVT performance such that sleep restriction
      resulted in slower and more variable response times, predominantly during the
      biological night. This interaction was not altered by prior wakefulness, as
      indicated by a nonsignificant sleep dose * circadian phase * prior wake
      interaction. CONCLUSIONS: The performance consequence of sleep restriction in our
      study was prominent during the biological night, even when the prior wake
      duration was short, and this performance consequence was in forms of waking state
      instability. This result is likely due to acute homeostatic sleep pressure
      remaining high despite the sleep episode.

PMID- 21731144
TI  - The effects of sleep extension on the athletic performance of collegiate
      basketball players.
AB  - STUDY OBJECTIVES: To investigate the effects of sleep extension over multiple
      weeks on specific measures of athletic performance as well as reaction time,
      mood, and daytime sleepiness. SETTING: Stanford Sleep Disorders Clinic and
      Research Laboratory and Maples Pavilion, Stanford University, Stanford, CA.
      PARTICIPANTS: Eleven healthy students on the Stanford University men's varsity
      basketball team (mean age 19.4 +/- 1.4 years). INTERVENTIONS: Subjects maintained
      their habitual sleep-wake schedule for a 2-4 week baseline followed by a 5-7 week
      sleep extension period. Subjects obtained as much nocturnal sleep as possible
      during sleep extension with a minimum goal of 10 h in bed each night. Measures of
      athletic performance specific to basketball were recorded after every practice
      including a timed sprint and shooting accuracy. Reaction time, levels of daytime
      sleepiness, and mood were monitored via the Psychomotor Vigilance Task (PVT),
      Epworth Sleepiness Scale (ESS), and Profile of Mood States (POMS), respectively.
      RESULTS: Total objective nightly sleep time increased during sleep extension
      compared to baseline by 110.9 +/- 79.7 min (P < 0.001). Subjects demonstrated a
      faster timed sprint following sleep extension (16.2 +/- 0.61 sec at baseline vs.
      15.5 +/- 0.54 sec at end of sleep extension, P < 0.001). Shooting accuracy
      improved, with free throw percentage increasing by 9% and 3-point field goal
      percentage increasing by 9.2% (P < 0.001). Mean PVT reaction time and Epworth
      Sleepiness Scale scores decreased following sleep extension (P < 0.01). POMS
      scores improved with increased vigor and decreased fatigue subscales (P < 0.001).
      Subjects also reported improved overall ratings of physical and mental well-being
      during practices and games. CONCLUSIONS: Improvements in specific measures of
      basketball performance after sleep extension indicate that optimal sleep is
      likely beneficial in reaching peak athletic performance.

PMID- 21731145
TI  - Equivalence of nasal and oronasal masks during initial CPAP titration for
      obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVE: Continuous positive airway pressure (CPAP) titration studies are
      commonly performed using a nasal mask but some patients may prefer a full-face or
      oronasal mask. There is little evidence regarding the equivalence of different
      mask interfaces used to initiate treatment. We hypothesized that oronasal
      breathing when using an oronasal mask increases upper airway collapsibility and
      that a higher pressure may be required to maintain airway patency. We also
      assessed patient preferences for the 2 mask interfaces. DESIGN: Prospective,
      randomized, cross-over design with 2 consecutive CPAP titration nights. SETTING:
      Accredited laboratory in a university hospital. PATIENTS OR PARTICIPANTS: Twenty
      four treatment-naive subjects with obstructive sleep apnea syndrome and
      respiratory disturbance index of greater than 15 events per hour. INTERVENTIONS:
      CPAP titration was performed using an auto-titrating machine with randomization
      to a nasal or oronasal mask, followed by a second titration night using the
      alternate mask style. MEASUREMENTS AND RESULTS: There was no significant
      difference in the mean pressures determined between nasal and oronasal masks,
      although 43% of subjects had nasal-to-oronasal mask-pressure differences of 2 cm
      H(2)O or more. Residual respiratory events, arousals, and measured leak were all
      greater with the oronasal mask. Seventy-nine percent of subjects preferred the
      nasal mask. CONCLUSIONS: Patients with obstructive sleep apnea syndrome can
      generally switch between nasal and oronasal masks without changing machine
      pressure, although there are individual differences that may be clinically
      significant. Measured leak is greater with the oronasal mask. Most patients with
      obstructive sleep apnea syndrome prefer a nasal mask as the interface for
      initiation of CPAP. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry (ANZCTR). ACTRN: ACTRN12611000243910. URL:
      http://www.ANZCTR.org.au/ACTRN12611000243910.aspx

PMID- 21731146
TI  - Heritability and mortality risk of insomnia-related symptoms: a genetic
      epidemiologic study in a population-based twin cohort.
AB  - STUDY OBJECTIVES: Our aim was to estimate heritability in phenotypic insomnia and
      the association between insomnia and mortality. DESIGN: Representative follow-up
      study. PARTICIPANTS: 1990 survey of the Finnish Twin Cohort (N = 12502 adults;
      1554 monozygotic and 2991 dizygotic twin pairs). MEASUREMENTS: Current insomnia
      related symptoms (insomnia in general, difficulty in initiating sleep, sleep
      latency, nocturnal awakening, early morning awakening, and non-restorative sleep
      assessed in the morning and during the day) were asked. Latent class analysis was
      used to classify subjects into different sleep quality classes. Quantitative
      genetic modelling was used to estimate heritability. Mortality data was obtained
      from national registers until end of April 2009. RESULTS: The heritability
      estimates of each symptom were similar in both genders varying from 34% (early
      morning awakening) to 45% (nocturnal awakening). The most parsimonious latent
      class analysis produced 3 classes: good sleepers (48%), average sleepers (up to
      weekly symptoms, 40%), and poor sleepers (symptoms daily or almost daily, 12%).
      The heritability estimate for the cluster was 46% (95% confidence interval 41% to
      50%). In a model adjusted for smoking, BMI, and depressive symptoms, the all
      cause mortality of poor sleepers was elevated (excess mortality 55% in men and
      51% in women). Further adjustment for sleep length, use of sleep promoting
      medications, and sleep apnea-related symptoms did not change the results.
      CONCLUSIONS: Insomnia-related symptoms were common in both genders. The symptoms
      and their clusters showed moderate heritability estimates. A significant
      association was found between poor sleep and risk of mortality, especially in
      those with somatic disease.

PMID- 21731147
TI  - The natural history of insomnia in the Ibadan study of ageing.
AB  - STUDY OBJECTIVES: To determine the incidence and risk factors for insomnia among
      an under-studied population of elderly persons in Sub-Saharan Africa. SETTING:
      Eight contiguous predominantly Yoruba-speaking states in south-west and north
      central Nigeria representing about 22% of the national population. PARTICIPANTS:
      1307 elderly community-dwelling persons, aged 65 years and older. MEASUREMENTS:
      Face-to-face assessment with the Composite International Diagnostic Interview,
      version 3 (CIDI.3) in 2007 and 12 months later in 2008 to determine the
      occurrence and risk factors of incident and persistent insomnia, defined as
      syndrome or symptom. RESULTS: The incidence of insomnia syndrome in 2008 at 12
      months was 7.97% (95% CI, 6.60-9.60), while that of insomnia symptom was 25.68%
      (22.68-28.66). Females were at elevated risk for both syndrome and symptom. Among
      persons with insomnia symptom or syndrome at the baseline, 47.36% (95% CI 43.07
      51.68) continued to have it one year later. Decreasing economic status was
      associated with increasing incidence of insomnia. Persons with chronic medical
      conditions at baseline were at increased risk for new onset of insomnia. Compared
      to persons with the lowest body mass index (BMI) (< 18.5), those with higher BMI
      were at elevated risk for persistence of their insomnia, with those in the obese
      range (>= 30) having a 4-fold risk. CONCLUSIONS: There is a high incidence and
      chronicity of insomnia in this elderly population. Persons with chronic health
      conditions are particularly at risk of new onset as well as persistence of
      insomnia.

PMID- 21731149
TI  - EFFECTS OF MATERNAL DEPRESSION AND PANIC DISORDER ON MOTHER-INFANT INTERACTIVE
      BEHAVIOR IN THE FACE-TO-FACE STILL-FACE PARADIGM.
AB  - The present study evaluated the interactive behavior of three groups of mothers
      and their 3-month-old infants in the Face-to-Face Still-Face paradigm. The
      mothers had either a clinical diagnosis of major depressive disorder (MDD, n =
      33) with no comorbidity, a clinical diagnosis of panic disorder (PD, n = 13) with
      no comorbidity, or no clinical diagnosis (n = 48). The sample was selected to be
      at otherwise low social and medical risk, and all mothers with PD or MDD were in
      treatment. The findings indicated that (a) infants of mothers with PD or MDD
      displayed the traditional still-face and reunion effects described in previous
      research with nonclinical samples; (b) the 3-month-old infants in this study
      showed similar, but not identical, gender effects to those described for older
      infants; and (c) there were no patterns of maternal or infant interactive
      behavior that were unique to the PD, MDD, or control groups. These results are
      discussed in light of mothers' risk status, receipt of treatment, severity of
      illness, and comorbidity of PD and MDD.

PMID- 21731150
TI  - An Integrative Pathway-based Clinical-genomic Model for Cancer Survival
      Prediction.
AB  - Prediction models that use gene expression levels are now being proposed for
      personalized treatment of cancer, but building accurate models that are easy to
      interpret remains a challenge. In this paper, we describe an integrative clinical
      genomic approach that combines both genomic pathway and clinical information.
      First, we summarize information from genes in each pathway using Supervised
      Principal Components (SPCA) to obtain pathway-based genomic predictors. Next, we
      build a prediction model based on clinical variables and pathway-based genomic
      predictors using Random Survival Forests (RSF). Our rationale for this two-stage
      procedure is that the underlying disease process may be influenced by
      environmental exposure (measured by clinical variables) and perturbations in
      different pathways (measured by pathway-based genomic variables), as well as
      their interactions. Using two cancer microarray datasets, we show that the
      pathway-based clinical-genomic model outperforms gene-based clinical-genomic
      models, with improved prediction accuracy and interpretability.

PMID- 21731151
TI  - Testing for Constant Nonparametric Effects in General Semiparametric Regression
      Models with Interactions.
AB  - We consider the problem of testing for a constant nonparametric effect in a
      general semi-parametric regression model when there is the potential for
      interaction between the parametrically and nonparametrically modeled variables.
      The work was originally motivated by a unique testing problem in genetic
      epidemiology (Chatterjee, et al., 2006) that involved a typical generalized
      linear model but with an additional term reminiscent of the Tukey one-degree-of
      freedom formulation, and their interest was in testing for main effects of the
      genetic variables, while gaining statistical power by allowing for a possible
      interaction between genes and the environment. Later work (Maity, et al., 2009)
      involved the possibility of modeling the environmental variable
      nonparametrically, but they focused on whether there was a parametric main effect
      for the genetic variables. In this paper, we consider the complementary problem,
      where the interest is in testing for the main effect of the nonparametrically
      modeled environmental variable. We derive a generalized likelihood ratio test for
      this hypothesis, show how to implement it, and provide evidence that our method
      can improve statistical power when compared to standard partially linear models
      with main effects only. We use the method for the primary purpose of analyzing
      data from a case-control study of colorectal adenoma.

PMID- 21731152
TI  - Heteroscedastic nonlinear regression models based on scale mixtures of skew
      normal distributions.
AB  - An extension of some standard likelihood based procedures to heteroscedastic
      nonlinear regression models under scale mixtures of skew-normal (SMSN)
      distributions is developed. We derive a simple EM-type algorithm for iteratively
      computing maximum likelihood (ML) estimates and the observed information matrix
      is derived analytically. Simulation studies demonstrate the robustness of this
      flexible class against outlying and influential observations, as well as nice
      asymptotic properties of the proposed EM-type ML estimates. Finally, the
      methodology is illustrated using an ultrasonic calibration data.

PMID- 21731153
TI  - Automated subject-specific, hexahedral mesh generation via image registration.
AB  - Generating subject-specific, all-hexahedral meshes for finite element analysis
      continues to be of significant interest in biomechanical research communities. To
      date, most automated methods "morph" an existing atlas mesh to match with a
      subject anatomy, which usually result in degradation in mesh quality because of
      mesh distortion. We present an automated meshing technique that produces
      satisfactory mesh quality and accuracy without mesh repair. An atlas mesh is
      first developed using a script. A subject-specific mesh is generated with the
      same script after transforming the geometry into the atlas space following rigid
      image registration, and is transformed back into the subject space. By meshing
      the brain in 11 subjects, we demonstrate that the technique's performance is
      satisfactory in terms of both mesh quality (99.5% of elements had a scaled
      Jacobian >0.6 while <0.01% were between 0 and 0.2) and accuracy (average distance
      between mesh boundary and geometrical surface was 0.07 mm while <1% greater than
      0.5mm). The combined computational cost for image registration and meshing was <4
      min. Our results suggest that the technique is effective for generating subject
      specific, all-hexahedral meshes and that it may be useful for meshing a variety
      of anatomical structures across different biomechanical research fields.

PMID- 21731154
TI  - Kochen-Specker theorem studied with neutron interferometer.
AB  - The Kochen-Specker theorem shows the incompatibility of noncontextual hidden
      variable theories with quantum mechanics. Quantum contextuality is a more general
      concept than quantum non-locality which is quite well tested in experiments using
      Bell inequalities. Within neutron interferometry we performed an experimental
      test of the Kochen-Specker theorem with an inequality, which identifies quantum
      contextuality, by using spin-path entanglement of single neutrons. Here
      entanglement is achieved not between different particles, but between degrees of
      freedom of a single neutron, i.e., between spin and path degree of freedom.
      Appropriate combinations of the spin analysis and the position of the phase
      shifter allow an experimental verification of the violation of an inequality
      derived from the Kochen-Specker theorem. The observed violation 2.291+/-0.008?1
      clearly shows that quantum mechanical predictions cannot be reproduced by
      noncontextual hidden variable theories.

PMID- 21731155
TI  - High angular resolution neutron interferometry.
AB  - The currently largest perfect-crystal neutron interferometer with six beam
      splitters and two interference loops offers novel applications in neutron
      interferometry. The two additional lamellas can be used for quantitative
      measurements of a phase shift due to crystal diffraction in the vicinity of a
      Bragg condition. The arising phase, referred to as "Laue phase," reveals an
      extreme angular sensitivity, which allows the detection of beam deflections of
      the order of 10(-6) s of arc. Furthermore, a precise measurement of the Laue
      phase at different reflections might constitute an interesting opportunity for
      the extraction of fundamental quantities like the neutron-electron scattering
      length, gravitational short-range interactions in the sub-micron range and the
      Debye Waller factor. For that purpose several harmonics can be utilized at the
      interferometer instrument ILL-S18.

PMID- 21731156
TI  - Improving the usability of intravenous medication labels to support safe
      medication delivery.
AB  - Medication label design is frequently a contributing factor to medication errors.
      Design regulations and recommendations have been predominantly aimed at
      manufacturers' product labels. Pharmacy-generated labels have received less
      scrutiny despite being an integral artifact throughout the medication use
      process. This article is an account of our efforts to improve the design of a
      hospital's intravenous (IV) medication labels. Our analysis revealed a set of
      interrelated processes and stakeholders that restrict the range of feasible label
      designs. The technological and system constraints likely vary among hospitals and
      represent significant barriers to developing and implementing specific design
      standards. We propose both an ideal IV label design and one that adheres to the
      current constraints of the hospital under study.

PMID- 21731157
TI  - Anthelminthic efficacy of aqueous extract of Acanthus montanus leaf against
      strongylid nematodes of small ruminants.
AB  - The anthelminthic efficacy of the crude aqueous extract of Acanthus montanus
      (Nees) T. Anders (Acanthaceae) against strongylid nematodes of small ruminants
      was investigated using the in-vitro egg hatch and larval growth inhibition
      assays. Faecal samples collected per rectum from sheep and goats were subjected
      to parasitological examination using the McMaster counting technique with a yield
      of 700 eggs per gram (E.P.G.) of faeces. Crude aqueous leaf extract of Acanthus
      montanus was extracted using cold water extraction with a yield of 13.01% w/w.
      Egg hatch assay revealed a 91.75% reduction in egg hatch at concentration of 25
      mg/ml of the extract. The extract had a 100% inhibition, at 200mg/ml
      concentration which was equivalent to the activity of 3.125 mg/ml albendazole.
      The distilled water control however, showed a 0% inhibition. Larval growth
      inhibition assay results showed the extract on Day 1 at 25 mg/ml and 200mg/ml
      concentrations yielded 67.02% and 85.26% larval inhibition. On Day 2, 100%
      inhibition was obtained on all concentrations of the extract except for 25 mg/ml
      that yielded 88.30%. Albendazole however, had a 100% larval inhibition for all
      concentrations on Day 2. A 100% larval inhibition was recorded on Day 3 from the
      25 mg/ml concentrations. The mean percentage larval inhibition of the extract at
      200mg/ml (92.63%) was comparable to the standard anthelminthic (albendazole) at
      12.50mg/ml (92.28%). These findings showed that there is a pharmacological basis
      for the folkloric claim of the anthelminthic effect of Acanthus montanus.

PMID- 21731158
TI  - Use of Strychnos nux-vomica (Azraqi) seeds in Unani system of medicine: role of
      detoxification.
AB  - Some plants used in Unani system of medicine are toxic, even deadly poisonous.
      The drugs having such plants as their components are detoxified before they are
      dispensed to the patients. One such drug, capsule Hudar, has Strychnos nux-vomica
      L. (Azraqi) seeds as one of its components and is very effectively used to
      elevate blood pressure. Ancient manuscripts describe many methods of its
      detoxification. It has been found that the detoxification processes studied
      reduce the strychnine content, as determined either by using uv-vis
      spectrophotometer or HPLC, present in Strychnos nux vomica seeds which is
      responsible for Strychnos nux vomica toxicity. The decrease in strychnine amount
      was best when the seeds were immersed for detoxification in excess of water for 5
      days, in milk for 2 days followed by their boiling in milk. Strychnine in small
      amounts has been reported to give subjective feeling of stimulation.

PMID- 21731159
TI  - Effects of Ginkgo biloba extract on free radical metabolism of liver in mice
      during endurance exercise.
AB  - This study investigated the effect of Ginkgo biloba extract on Free Radical
      Metabolism of Liver in mice during endurance exercise. Forty-eight mice were
      divided into the quiet group and the exercised group. And the two groups were
      both grouped again, including the control group and the drug-treated group. After
      exhaustive exercise, the exercised groups were subdivided into the immediate
      group and the recovery group. The swimming time to exhaustion significantly
      prolonged in the exercised drug-treated group as compared with the exercised
      control group (P < 0.05); The SOD activity of drug-treated groups significantly
      increased (P < 0.05) as compared with the control groups and MDA content was
      significantly lower (P < 0.05). The SOD activity and MDA content of exercised
      control groups significantly increased (P < 0.05) as compared with the quiet
      control group. The SOD activity and MDA content of exercised drug-treated groups
      significantly increased (P < 0.05) as compared with the quiet drug-treated group.
      The results indicated that Ginkgo biloba extract can obviously increase the
      body's endurance exercise capacity in mice and delay fatigue; Ginkgo biloba
      extract can help to increase the activity of the antioxidant enzymes in liver
      tissue, reduce the lipid peroxidation injury in liver tissue caused by free
      radicals, improve athletic ability, and promote the recovery process after
      exercise in mice.

PMID- 21731160
TI  - In vitro antioxidant activity of extracts from the leaves of Felicia muricata
      thunb. An underutilized medicinal plant in the Eastern Cape Province, South
      Africa.
AB  - Felicia muricata is a medicinal plant used for the management of different human
      and livestock diseases in the Eastern Cape Province of South Africa. The
      antioxidant potential of the leaves from this herb was investigated using its
      water, methanol, acetone and ethanol extracts. All the extracts were rich in
      phenols, proanthocyanidins and flavonols but low in flavonoids. The water extract
      exhibited low DPPH scavenging activity while the methanol, acetone and ethanol
      extracts showed higher activities. Again all the extracts showed high ABTS
      scavenging activity with a correlation between total phenolic content (R2 =
      0.9965), DPPH (R2 = 0.982) and ABTS (R2 = 0.927). Traditionally, however, plant
      extracts are prepared with water as infusions, decoction and poultice. Our
      results have shown that both the water and ethanol extracts from Felicia muricata
      displayed strong antioxidant activity. Therefore, it would seem likely that both
      solvents were able to extract those compounds which are responsible for the
      antioxidant activity of F. muricata.

PMID- 21731161
TI  - Antimicrobial activity of essential oils of Physalis angulata. L.
AB  - The need for a reduction in drug resistance led to the investigation of Argemone
      Mexicana L. as an agent against Bacillus subtilis, Klebsiella pneumoniae,
      Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida
      stellatoidea and Candida torulopsis, using well diffusion and minimum inhibitory
      concentrations methods. The sensitivity of Bacillus Subtilis, Klebsiella
      pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus to the essential
      oils of both the aerial and root parts were determined. Pseudomonas aeruginosa
      was resistant to the essential oil from both the aerial and root part of the
      plant. C. torulopsis, C. stellatoidea and C. albicans were susceptible to the
      essential oils from the aerial and root part of the plant. The minimum inhibitory
      concentrations ranging between 3.75 mg/ml and 4.0 mg/ml were recorded for
      Bacillus subtilis, Klebsiella pneumoniae by the aerial and the root extracts, but
      P. aeruginosa and S. aureus were not susceptible to the aerial and root extracts.
      The observed inhibition of selected bacteria and fungi by oils of Physalis
      angulata makes it a promising antimicrobial agent. This study justifies its uses
      for treatment of sores, cuts, intestinal and digestive problems and some skin
      diseases often reported in folkloric medicine.

PMID- 21731162
TI  - Effect of Achyranthes bidentata polysaccharides on the expression of BCL-2 and
      bax in hepatic tissues after exhaustive exercise in rats.
AB  - This study aims to assess the effects of Achyranthes bidentata polysaccharides
      (ABPS) on the expression of bcl-2 and bax in hepatic tissues after exhaustive
      exercise in order to provide theoretical support for the application of ABPS in
      the field of sports nutrition. Thirty male Sprague-Dawley rats were randomized
      into three groups, each consisting of 10 rats: Normal control group (NCG),
      Exhausting exercises control group (EECG), ABPS treated group (ATG). ABPS were
      fed orally by gastric intubation to rats of ABPS treated group (ATG) once daily
      for 7 days. Control animals (EECG and NCG) received the same amount of isotonic
      sodium chloride solution. Exhaustive exercise was performed on a rodent
      treadmill. The SP (streptavidin peroxidase) method for immunohistochemical
      staining was adopted to test the protein expression of bax and bcl-2 in the
      hepatic tissues of the rats. Exhausting exercises increased bax protein
      expression of hepatic tissues of rats and bax/bcl-2 ratio dramatically, but a
      decreased bcl-2 protein expression. In the rats fed ABPS orally by gastric
      intubation, the bax protein expression and bax/bcl-2 ratio obviously decreased,
      while bcl-2 protein expression increased. The result indicated that bax and bcl-2
      co-regulated the exercise-induced hepatocyte apoptosis. Feeding ABPS orally by
      gastric intubation to rats can inhibit the hepatocyte apoptosis in exhaustive
      exercise.

PMID- 21731163
TI  - The potential role of honey and its polyphenols in preventing heart diseases: a
      review.
AB  - Honey is rich in phenolic compounds, which act as natural antioxidants and are
      becoming increasingly popular because of their potential role in contributing to
      human health. A wide range of phenolic constituents is present in honey like
      quercetin, caffeic acid phenethyl ester (CAPE), acacetin, kaempferol, galangin
      which have promising effect in the treatment of cardiovascular diseases. Many
      epidemiological studies have shown that regular intake of phenolic compounds is
      associated with reduced risk of heart diseases. In coronary heart disease, the
      protective effects of phenolic compounds include mainly antithrombotic, anti
      ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids
      decrease the risk of coronary heart disease by three major actions: improving
      coronary vasodilatation, decreasing the ability of platelets in the blood to
      clot, and preventing low-density lipoproteins (LDLs) from oxidizing. In this
      review paper, we discussed the preventive role of polyphenols of honey against
      cardiovascular diseases.

PMID- 21731164
TI  - Use of complementary and alternative medicine by cancer patients at Zhejiang
      University Teaching Hospital Zhuji Hospital, China.
AB  - Complementary and alternative medicine (CAM) is garnering increasing interest and
      acceptance among the general population throughout the world. The use of CAM by
      cancer patients is very common in China. The referenced English literature has no
      rural community-based study from China on this subject. This study was conducted
      to define the prevalence, pattern of use, and reasons for using CAM by cancer
      patients at Zhejiang University Teaching Hospital Zhuji Hospital (ZUTH-ZJH),
      China. Face-to-face interviews using a structured questionnaire were used to
      determine the use of CAM by cancer patients. All consenting cancer patients were
      interviewed as they presented at the Department of Surgical Oncology of ZUTH-ZJH,
      from September 2009 to February 2010. One hundred and twenty one patients were
      interviewed; 64 (52.9%) were males and 57 (47.1%) were females. One hundred and
      thirteen patients (93.4%) have used CAM at some time during their current cancer
      illness, fifty two (46.0%) are female and sixty one (54.0%) are male patients; 8
      (6.6%) patients have not used any form of CAM. Chinese medicine (73.5.0%) was the
      most commonly reported CAM modality. Over 71.7% of those who used CAM were
      satisfied, only 28.3% were disappointed. Twenty eight users (24.8%) did not see
      any benefit from the CAM, but eighty one patients (71.7%) could describe some
      specific benefits. Only one patient will use orthodox medicine instead of CAM in
      the future, almost all patients will continue to use CAM in the future. CAM use
      is very common among cancer patients in local area of China. Most users obtain
      the expected benefits, and adverse events are uncommon. It is imperative that
      oncologists should explore the use of CAM with their cancer patients and work
      towards an integrated model of health-care provision. This knowledge will enable
      oncologists to better counsel the patients.

PMID- 21731165
TI  - Protection of Chinese herbs against adenine-induced chronic renal failure in
      rats.
AB  - The aim of the study is to evaluate the efficacy of Chinese herbs (Angelica
      sinensis, Ligusticum wallichii, Salvia miltiorrhiza, Rhizoma dioscoreae, Rhodiola
      crenilata, Astragalus membranaceus and Angelica sinensis) on adenine-induced
      chronic renal failure in rats. 30 age-matched male Wistar rats were divided into
      three groups. Rats in group A (n = 10), B (n = 10) and C (n = 10) were fed a
      standard laboratory chow and allowed tap water ad libitum. In group B and C,
      renal failure was induced by the administration of a diet containing 0.75%
      adenine for 28 days which began at day 0. Rats in group C were given Chinese
      herbs (40 ml/kg with drug concentration 1.75 g/ml) beginning at day 0. Urine
      albumin, blood urea nitrogen (BUN) and creatinine were determined at days 0, 14
      and 28. At day 28, the animals were killed and their kidneys removed for light
      microscope evaluation. Body weight in Group B decreased more significantly than
      that in Group C (p = 0.032) at day 28. The rats in group B demonstrated more
      severe proteinuria and higher Serum creatinine and BUN levels than group C at day
      14 and day 28 (P < 0.05, 0.01). All rats given adenine developed marked
      structural renal damage involving the tubule and interstitium. The values were
      much less severe in group C than those in group B. In adenine-induced chronic
      renal failure rats, the protective effects of these Chinese herbs were of a
      significant nature. Our results do support the notion that these Chinese herbs
      are useful in deferring the advance of chronic renal failure. We recommend
      Chinese herbs as a beneficial treatment for pre-end stage chronic renal failure.

PMID- 21731166
TI  - Comparison of anti-inflammatory and anti-nociceptive activities of Curcuma
      wenyujin Y.H. Chen et C. Ling and Scutellaria baicalensis Georgi.
AB  - The study aimed to compare the anti-inflammatory and anti-nociceptive activities
      of Curcuma wenyujin Y.H. Chen et C. Ling (Curcuma wenyujin) and Scutellaria
      baicalensis Georgi (Scutellaria baicalensis). This study used three parts to
      compare the two herbs. Firstly, animals were randomly divided into a Scutellaria
      baicalensis group, a Curcuma wenyujin group, an indomethacin group, and a model
      control group to perform an ear edema test, a carrageenin-induced paw edema test,
      a cotton pellet-induced granuloma formation test, and an acetic acid-induced
      writhing test. Secondly, model rats with pelvic inflammation were established,
      and the serum levels of TNF-alpha and IL-6 in each group was detected with the
      Enzyme-Linked Immunosorbent Assay (ELISA). Thirdly, pharmacokinetics analysis of
      Scutellaria baicalensis and Curcuma wenyujin was conducted on the model rats. The
      ear edema test, carrageenin-induced paw edema test, cotton pellet-induced
      granuloma formation test, and acetic acid-induced writhing test all showed that
      Curcuma wenyujin had stronger anti-inflammatory and anti-nociceptive effects than
      Scutellaria baicalensis. There is significant difference between the effects of
      Curcuma wenyujin and Scutellaria baicalensis on the levels of TNF-alpha and IL-6
      for the model rats. Curcuma wenyujin decreased the levels of TNF-alpha and IL-6
      more than Scutellaria baicalensis. The pharmacokinetics analysis showed that
      curcumol's Tmax, Cmax, and the area under the curve (AUC) were all higher than
      baicalin's. This study indicated that for pelvic inflammation, Curcuma wenyujin
      had better anti-inflammatory and anti-nociceptive effects than Scutellaria
      baicalensis.

PMID- 21731167
TI  - Evaluation of the toxicity and reversibility profile of the aqueous seed extract
      of Hunteria umbellata (K. Schum.) Hallier f. in rodents.
AB  - Hunteria umbellata (K. Schum.) Hallier f. (family: Apocynaceae) is reputed for
      the folkloric management of labour, pain and swellings, stomach ulcers, diabetes,
      obesity, and anaemia, with no scientific report of its toxicity and reversibility
      profile. The present study was, therefore, aimed at investigating the in vivo
      toxicity and reversibility profile of the aqueous seed extract of Hunteria
      umbellata (HU). The acute oral and intraperitoneal toxicity studies of HU were
      determined in Swiss albino mice while its 90-day oral toxicity and toxicity
      reversibility profile on anthropometric, biochemical, haematological and
      histopathological parameters were also assessed using standard procedures.
      Results showed that the LD50 values for the acute oral and intraperitoneal
      toxicity studies for HU were estimated to be 1000 mg/kg and 459.3 mg/kg,
      respectively. Visible signs of immediate and delayed toxicities including starry
      hair coat, respiratory distress, and dyskinesia were observed. For the chronic
      oral toxicity study, HU administered for 90 days produced significant (p < 0.001)
      reductions in the weight gain pattern and significant (p < 0.001) and dose
      related increases in the relative weights of liver, stomach, spleen, testis,
      lungs and heart, at the 100 and 500 mg/kg of HU. Chronic HU treatment also
      produced significant (p < 0.05, p < 0.001) dose related reductions in the serum
      levels of fasting blood glucose, bicarbonate, urea and creatinine while causing
      non-significant (p > 0.05) alterations in the serum levels of sodium, potassium,
      alaninine transaminase, aspartate transaminase, alkaline phosphatase, total and
      conjugated bilirubin, total protein and albumin. Also, chronic oral treatment
      with HU produced significant (p < 0.05, p < 0.01, p < 0.001) and dose-related
      increases in the red cell count, packed cell volume, haemoglobin concentration,
      platelet count, total leucocyte count and lymphocyte differential while producing
      significant (p < 0.05) reductions in neutrophil and granulocyte differentials. HU
      also produced histological features of proliferations of the stomach epithelia,
      lung tissues, splenic white and red pulps, and testicular spermatogenic series.
      Following 14 days of oral toxicity reversibility test, there was no significant
      (p>0.05) reversal in the serum levels of the biochemical and haematological
      parameters investigated, including the HU-induced histological lesions. Overall,
      results of this study showed that HU has a relatively low oral toxicity profile
      but its prolonged use, particularly, at high doses should be with great caution.

PMID- 21731168
TI  - Chemotherapeutic interaction between Khaya grandifoliola (WELW) CDC stem bark
      extract and two anti-malarial drugs in mice.
AB  - In malarial endemic countries especially in the tropics, conventional
      antimalarial drugs are used with herbal remedies either concurrently or
      successively. Khaya grandifoliola is one of such popular herbs used in the
      treatment of malaria.Various doses of ethanol extract of K. grandifoliola stem
      bark (50-400 mg/kg/day) were administered orally to Swiss albino mice infected
      with Plasmodium yoelii nigerense. A dose of 100 mg/kg/day of the extract was also
      combined with 2.5 mg/kg/day of chloroquine or 6.25 mg/kg/day of halofantrine in
      both early and established malaria infection test models. The results showed that
      in the early malaria infection test, K. grandifoliola in combination with
      chloroquine or halofantrine elicited enhanced antiplasmodial effect in the
      established infection, there was significantly greater parasite clearance
      following administration of the combination when compared to the effects of K.
      grandifoliola or the conventional drugs alone. The mean survival period of
      parasitized animals was also enhanced by the extract/halofantrine combination.
      Lower therapeutic doses of halofantrine may be required to potentiate parasite
      clearance when used in combination with K. grandifoliola. This may constitute
      great advantage to halofantrine which is associated with cardiotoxicity at high
      doses.

PMID- 21731170
TI  - Identification Problems in Personality Psychology.
AB  - This paper discusses and illustrates identification problems in personality
      psychology. The measures used by psychologists to infer traits are based on
      behaviors, broadly defined. These behaviors are produced from multiple traits
      interacting with incentives in situations. In general, measures are determined by
      these multiple traits and do not identify any particular trait unless incentives
      and other traits are controlled for. Using two data sets, we show, as an example,
      that substantial portions of the variance in achievement test scores and grades,
      which are often used as measures of cognition, are explained by personality
      variables.

PMID- 21731171
TI  - Empirical Research on Factors Related to the Subjective Well-Being of Chinese
      Urban Residents.
AB  - Data from the China General Social Survey are used in order to investigate the
      factors that are related to the subjective well-being of Chinese urban residents.
      Factors predicting higher subjective well-being include female gender, high
      income class, marriage, employment, fashionable consumption, less sense of
      relative deprivation, and party membership. Among these, the sense of relative
      deprivation has the strongest explanatory power. This suggests that the most
      direct threat to current subjective well-being in urban China is that its
      residents are living in a society with dramatic change, competition and
      increasing inequalities.

PMID- 21731172
TI  - Academic Success of Mexican Origin Adolescent Boys and Girls: The Role of
      Mothers' and Fathers' Parenting and Cultural Orientation.
AB  - To understand the role that Mexican origin parents play in their children's
      academic success, this study used structural equation modeling to evaluate the
      associations of parents' parenting practices (warmth, monitoring, harshness, and
      academic involvement) and cultural orientations (enculturation and acculturation)
      with their adolescents' grades, classroom behavior, and association with peers
      who get into trouble at school. Data were obtained from teachers, mothers,
      fathers, and male and female adolescents in 560 Mexican origin families living in
      the southwest U.S. Results indicated that mothers' and fathers' parenting
      practices and cultural orientations were linked to adolescents' academic
      outcomes. However, there were differences for boys and girls. Results are
      discussed in relation to parent and adolescent gender roles and implications for
      intervention.

PMID- 21731173
TI  - Synthesis of H-Labeled Tetrabenazine (TBZ).
AB  - Tetrabenazine (TBZ) (1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H
      benzo[a]quinolin-2-one), a vesicular monamine transporter 2 inhibitor, was
      prepared as a tritium-labeled compound with high specific activity and
      radiochemical purity. Catalytic hydrogenation of a precursor with the terminal
      double bond was used to introduce the tritium. This method provides tritium
      labeled TBZ with high specific activity and radiochemical purity, which allow the
      further investigation of a TBZ in the neurological field.

PMID- 21731174
TI  - Dimension reduced kernel estimation for distribution function with incomplete
      data.
AB  - This work focuses on the estimation of distribution functions with incomplete
      data, where the variable of interest Y has ignorable missingness but the
      covariate X is always observed. When X is high dimensional, parametric approaches
      to incorporate X - information is encumbered by the risk of model
      misspecification and nonparametric approaches by the curse of dimensionality. We
      propose a semiparametric approach, which is developed under a nonparametric
      kernel regression framework, but with a parametric working index to condense the
      high dimensional X - information for reduced dimension. This kernel dimension
      reduction estimator has double robustness to model misspecification and is most
      efficient if the working index adequately conveys the X - information about the
      distribution of Y. Numerical studies indicate better performance of the
      semiparametric estimator over its parametric and nonparametric counterparts. We
      apply the kernel dimension reduction estimation to an HIV study for the effect of
      antiretroviral therapy on HIV virologic suppression.

PMID- 21731175
TI  - Psychologist suicide: Incidence, impact, and suggestions for prevention,
      intervention, and postvention.
AB  - Psychologist practitioners are not immune to some mental health problems,
      including suicidality, for which they provide services. In the aftermath of two
      recent psychologist suicides, the American Psychological Association's Advisory
      Committee on Colleague Assistance (ACCA) initiated the formation of a conjoint ad
      hoc committee consisting of members from ACCA, the American Psychological
      Association (APA) Practice Directorate, and the Section on Clinical Emergencies
      and Crises (Section VII of APA's Division 12) to investigate the incidence of
      psychologist suicide and its impact on colleagues, students or interns, patients
      or clients, and the profession. The committee reviewed the extant empirical
      literature on suicide rates for psychologists, evaluated unpublished data on
      psychologist suicide provided by the National Institute of Occupational Safety
      and Health (NIOSH), interviewed colleague survivors, reviewed published case
      reports of the impact of therapist suicides, and linked their findings to the
      literature on professional distress, impairment, and self-care. The committee
      concluded that there is evidence suggestive of an elevated risk of suicide for
      psychologists in past decades. It further concluded that there is a need for
      further research to confirm if there is a heightened risk of suicide for
      psychologists in the present day, and to determine factors that might contribute
      to such risk. Accounts from colleague-survivors suggest that the impact of a
      psychologist's suicide can affect many people including family, colleagues,
      students, and patients or clients. This article offers suggestions for possible
      preventive approaches, for intervention with potentially at-risk colleagues, and
      for postvention efforts in the wake of a colleague suicide.

PMID- 21731176
TI  - Gesturing makes memories that last.
AB  - When people are asked to perform actions, they remember those actions better than
      if they are asked to talk about the same actions. But when people talk, they
      often gesture with their hands, thus adding an action component to talking. The
      question we asked in this study was whether producing gesture along with speech
      makes the information encoded in that speech more memorable than it would have
      been without gesture. We found that gesturing during encoding led to better
      recall, even when the amount of speech produced during encoding was controlled.
      Gesturing during encoding improved recall whether the speaker chose to gesture
      spontaneously or was instructed to gesture. Thus, gesturing during encoding seems
      to function like action in facilitating memory.

PMID- 21731177
TI  - Adherence of Escherichia coli O157:H7 to epithelial cells in vitro and in pig gut
      loops is affected by bacterial culture conditions.
AB  - The objectives of this study were to determine the effect of bacterial culture
      conditions on adherence of enterohemorrhagic Escherichia coli (EHEC) O157:H7
      strain 86-24 in vivo to pig enterocytes and to compare the results with adherence
      in vitro to cultured HEp-2 and IPEC-J2 cells. Growth of O157:H7 in MacConkey
      broth (MB) resulted in almost no adherence to both HEp-2 and IPEC-J2 cells; prior
      exposure of the bacteria to pH 2.5 reduced adherence. There was greater adherence
      by bacteria from static cultures than by those from shaken cultures and by
      bacteria cultured in brain-heart infusion (BHI) plus NaHCO3 (BHIN) than by
      bacteria cultured in BHI. In contrast, in pig ileal loops, bacteria cultured in
      MB adhered well to enterocytes, and prior exposure to pH 2.5 had no effect on
      adherence. Among several media tested for their effect on bacterial adherence in
      the pig intestine, MB and BHIN proved to be the best. Bacterial adherence was
      dose-dependent and was more extensive in the ileum than in the colon. This study
      demonstrated that there are remarkable differences between culture conditions
      that promote adherence of an EHEC O157:H7 strain in vitro and in vivo, that
      culture conditions profoundly affect adherence to epithelial cells in vitro and
      in vivo, and that pig ileal loops are better suited to adherence studies than are
      colon loops.

PMID- 21731178
TI  - Antimicrobial susceptibility of Clostridium perfringens isolates of bovine,
      chicken, porcine, and turkey origin from Ontario.
AB  - Antimicrobial susceptibilities and toxin types were determined for 275
      Clostridium perfringens isolates collected in Ontario in the spring of 2005.
      Minimal inhibitory concentrations (MICs) of C. perfringens isolates for 12
      antimicrobials used in therapy, prophylaxis, and/or growth promotion of cattle (n
      = 40), swine (n = 75), turkeys (n = 50), and chickens (n = 100) were determined
      using the microbroth dilution method. Statistical analyses and MIC distributions
      showed reduced susceptibility to bacitracin, clindamycin, erythromycin,
      florfenicol, and tetracycline for some isolates. Reduced susceptibility to
      bacitracin was identified in chicken (64%) and turkey (60%) isolates. Swine
      isolates had predominantly reduced susceptibility to clindamycin (28%) and
      erythromycin (31%), whereas bovine isolates had reduced susceptibility to
      clindamycin (10%) and florfenicol (10%). Reduced susceptibility to tetracycline
      was spread across all species. No clear reduced susceptibility, but elevated
      MIC(50) for virginiamycin was found in chicken isolates in comparison with
      isolates from other species. Toxin typing revealed that C. perfringens type A is
      the dominant toxin type isolated in this study across all 4 host species.

PMID- 21731179
TI  - Vaccination with type III secreted proteins leads to decreased shedding in calves
      after experimental infection with Escherichia coli O157.
AB  - Escherichia coli O157:H7 remains a threat to humans via cattle-derived fecal
      contamination of food and water. Preharvest intervention strategies represent a
      means of reducing the pathogen burden before harvest. In this study, the efficacy
      of a commercially produced type III secreted protein (TTSP) vaccine was evaluated
      with the use of a commingled experimental calf infection model (30 placebo
      treated animals and 30 vaccinates). The calves were vaccinated on days 0, 21, and
      42 and infected with 10(9) colony-forming units (CFU) of E. coli O157 by oral
      gastric intubation on day 56. Fecal shedding was monitored daily for 14 d.
      Serologic assessment revealed a robust immune response to vaccination; the serum
      titers of antibodies against EspA, Tir, and total TTSPs were significantly higher
      in the vaccinates than in the placebo-treated animals on days 21, 42, 56, and 70.
      Significantly less (P = 0.011) of the challenge organism was shed by the
      vaccinates than by the placebo-treated animals on days 3 to 10. Peak shedding
      occurred in both groups on days 3 to 6; during this period the vaccinates showed
      a mean log reduction of 1.4 (P = 0.002) and a mitigated fraction of 51%. The
      number of animals shedding was significantly lower among the vaccinates compared
      with the placebo group on days 3 to 6 (P <= 0.05), with a mean prevented fraction
      of 21%. No differences in the duration of shedding were observed. Owing to the
      low challenge shedding in both groups on days 11 to 14 (mean CFU/g < 10; median =
      0), no significant differences were observed. These data indicate that TTSP
      vaccination had protective effects through significant reductions in the number
      of animals shedding and the number of challenge organisms shed per animal and
      provides evidence that TTSP vaccination is an effective preharvest intervention
      strategy against E. coli O157.

PMID- 21731180
TI  - Microbiological identification and analysis of swine tonsils collected from
      carcasses at slaughter.
AB  - The primary objective of this 7-month study was to determine the prevalence of
      porcine pathogens of the tonsil of the soft palate of swine at slaughter.
      Additional objectives were to determine if sampling the carcasses of normal or
      abnormal hogs provided different microbiological profiles and if the slaughter
      plant provides a feasible sampling frame and environment for detecting and
      monitoring important pathogens in tonsils that have health implications for both
      swine and humans. A total of 395 samples were collected from 264 farms. Of these,
      180 tonsils were collected from normal carcasses and 215 tonsils were collected
      from carcasses that were diverted to the hold rail. Laboratory testing included
      bacteriological culture and identification as well as real time-polymerase chain
      reaction (PCR) testing for porcine reproductive and respiratory syndrome virus
      (PPRSV) and immunohistochemistry (IHC) for porcine circovirus-2 (PCV-2). The most
      commonly isolated bacteria included: Streptococcus suis (53.7%), Arcanobacterium
      pyogenes (29.9%), Pasteurella multocida (27.3%), and Streptococcus porcinus
      (19.5%). Virus screening revealed evidence of PRRSV and PCV-2 in 22.0% and 11.9%
      of the samples, respectively. Salmonella Typhimurium and Yersinia enterocolitica
      were isolated in 0.5% and 1.8% of the samples, respectively. Tonsils collected
      from the hold rail were more likely to be positive for Staphylococcus hyicus
      [odds ratio (OR) = 7.51, confidence interval (CI) = 2.89 to 19.54], Streptococcus
      porcinus (OR = 9.93, CI = 4.27 to 23.10), and Streptococcus suis (OR = 2.16, CI =
      1.45 to 3.24). Tonsils collected from abnormal carcasses were less likely to be
      positive for Staphylococcus aureus (OR = 0.05, CI = 0.005 to 0.482).

PMID- 21731181
TI  - Estimated within-herd prevalence (WHP) of Mycobacterium avium subsp.
      paratuberculosis in a sample of Minnesota dairy herds using bacterial culture of
      pooled fecal samples.
AB  - The objective of this study was to describe the estimated within-herd prevalence
      (WHP) of Mycobacterium avium subsp. paratuberculosis (Map) in a sample of
      infected dairy herds in Minnesota (N = 66) using test results from bacterial
      culture of pooled fecal samples. Fecal samples were collected from up to 100 cows
      in each herd and were tested using bacterial culture in pools of 5 cows based on
      age order. The mean herd size was 222 (44 to 1500) milking cows; the cows were
      predominantly Holstein. Using a frequentist approach, the within-herd mean
      individual fecal prevalence was 10% [95% confidence interval (CI) = 4% to 16%]
      assuming 70% test sensitivity and 99.5% test specificity. Using Bayesian methods,
      the estimated true within-herd individual cow prevalence was 14% (95% CI = 7% to
      27%). Within-herd prevalence was higher in larger dairy herds than in herds with
      fewer cows. As Map is the causative agent of Johne's disease (JD), the results of
      this study could contribute to the success of a nationwide control program for
      this disease.

PMID- 21731182
TI  - Antimicrobial resistance in enteric pathogens isolated from Minnesota pigs from
      1995 to 2004.
AB  - This study investigated the occurrence and antimicrobial resistance profiles of
      Escherichia coli and Salmonella sp. isolated from swine samples submitted to the
      Minnesota Veterinary Diagnostic Laboratory (MVDL) in Saint Paul, Minnesota from
      1995 to 2004. During this time period, a total of 5072 E. coli and 2793
      Salmonella sp. was isolated. Most of these isolates were found to be resistant to
      the tetracycline and beta-lactam group of antibiotics. Resistance to
      spectinomycin was also frequently observed. An increasing trend in ampicillin
      resistance and a decreasing trend in apramycin resistance were seen in both
      pathogens, although ampicillin resistance was relatively higher in E. coli than
      in Salmonella. Aminoglycoside (amikacin) and quinolone (enrofloxacin) were the
      only antimicrobials to which minimum or no resistance was observed. The
      resistance of pig pathogens to several antibiotics indicates the need to
      routinely monitor the use of these antimicrobials and their associated resistance
      in pig populations.

PMID- 21731183
TI  - One-step reverse-transcription loop-mediated isothermal amplification for
      detection of infectious bursal disease virus.
AB  - A fast, sensitive, and specific reverse-transcription (RT) loop-mediated
      isothermal amplification (RT-LAMP) assay was developed that involved a single
      tube and a 1-step reaction for detecting infectious bursal disease virus (IBDV).
      Four specific primers were used for amplification of the VP2 gene of IBDV. The
      amplified LAMP products were detected by DNA electrophoresis and by direct
      observation with the naked eye in the presence of SYBR Green I. The sensitivity
      of RT-LAMP was determined to be 0.01 fg of IBDV viral RNA. This assay for IBDV is
      more sensitive than the conventional RT-polymerase chain reaction assay, which
      has a detection limit of 1 ng. The LAMP assay was also assessed for specificity
      and was found to precisely discriminate between positive and negative test
      samples. This newly established LAMP assay, combined with RT, is a practical
      diagnostic tool because IBDV-infected and uninfected clinical samples collected
      from an experimental farm could be discriminated. Full verification of a sample's
      IBDV status was obtained within 40 min of extraction of the viral RNA, which
      could then be directly added to the RT-LAMP reaction mixture.

PMID- 21731184
TI  - Assessment of a bone biopsy technique for measuring tiludronate in horses: a
      preliminary study.
AB  - This study assessed the feasibility of measuring tiludronate in horses using a
      minimally invasive bone biopsy technique. Eight horses were treated with
      intravenous (IV) tiludronate [1 mg/kg bodyweight (BW)], either once (n = 4) or
      twice, 28 d apart (n = 4). The horses that were treated once were euthanized on
      days 1, 43, 57, or 92 and those that were treated twice, were euthanized on days
      112, 154, 194, or 364. Bone samples were taken bilaterally from each horse at 4
      sites: the third metacarpal bone (MCIII), the 13th rib (R13), the tuber coxae
      (TC), and the cuboid bone (CB). Test samples were taken with a 5-mm diameter
      dental drill, while larger reference samples were taken with an osteotome. The
      concentrations of tiludronate were measured by high performance liquid
      chromatography (HPLC) with ultraviolet (UV) detection. The TC was the easiest
      site to sample, and no technical difficulties were encountered for extraction and
      measurement. Drill sampling at the MCIII was difficult. Moreover, both the
      extraction and measurement caused technical problems and results were unreliable
      in most cases (93%). Drill samples obtained from the R13 were very small and
      access to the CB required considerable dissection, which would not be feasible in
      vivo. Forty-six percent and 36% of the tiludronate measurements performed on the
      R13 and CB samples, respectively, were unreliable. The ratio of tiludronate
      concentrations ranged from 73% to 185% (median: 118%) in the TC, 65% to 208%
      (median: 81%) in the R13, and 26% to 110% (median: 57%) in the CB. In all but 1
      horse, the highest concentrations of tiludronate were found in the TC. It was
      concluded that bone biopsies performed at the TC were adequate for measuring
      tiludronate in horses and should be considered in future for repeated
      measurements over time in living animals.

PMID- 21731185
TI  - Mitochondrial transcription factor A (Tfam) gene sequencing and mitochondrial
      evaluation in inherited retinal dysplasia in miniature schnauzer dogs.
AB  - Mitochondrial transcription factor A (Tfam) has been implicated in the
      pathogenesis of retinal dysplasia in miniature schnauzer dogs and it has been
      proposed that affected dogs have altered mitochondrial numbers, size, and
      morphology. To test these hypotheses the Tfam gene of affected and normal
      miniature schnauzer dogs with retinal dysplasia was sequenced and lymphocyte
      mitochondria were quantified, measured, and the morphology was compared in normal
      and affected dogs using transmission electron microscopy. For Tfam sequencing,
      retina, retinal pigment epithelium (RPE), and whole blood samples were collected.
      Total RNA was isolated from the retina and RPE and reverse transcribed to make
      cDNA. Genomic DNA was extracted from white blood cell pellets obtained from the
      whole blood samples. The Tfam coding sequence, 5' promoter region, intron1 and
      the 3' non-coding sequence of normal and affected dogs were amplified using
      polymerase chain reaction (PCR), cloned and sequenced. For electron microscopy,
      lymphocytes from affected and normal dogs were photographed and the mitochondria
      within each cross-section were identified, quantified, and the mitochondrial area
      (MUm2) per lymphocyte cross-section was calculated. Lastly, using a masked
      technique, mitochondrial morphology was compared between the 2 groups. Sequencing
      of the miniature schnauzer Tfam gene revealed no functional sequence variation
      between affected and normal dogs. Lymphocyte and mitochondrial area,
      mitochondrial quantification, and morphology assessment also revealed no
      significant difference between the 2 groups. Further investigation into other
      candidate genes or factors causing retinal dysplasia in the miniature schnauzer
      is warranted.

PMID- 21731186
TI  - Epidural analgesia with morphine or buprenorphine in ponies with
      lipopolysaccharide (LPS)-induced carpal synovitis.
AB  - This study evaluated the analgesia effects of the epidural administration of 0.1
      mg/kg bodyweight (BW) of morphine or 5 MUg/kg BW of buprenorphine in ponies with
      radiocarpal joint synovitis. Six ponies were submitted to 3 epidural treatments:
      the control group (C) received 0.15 mL/kg BW of a 0.9% sodium chloride (NaCl)
      solution; group M was administered 0.1 mg/kg BW of morphine; and group B was
      administered 5 MUg/kg BW of buprenorphine, both diluted in 0.9% NaCl to a total
      volume of 0.15 mL/kg BW administered epidurally at 10 s/mL. The synovitis model
      was induced by injecting 0.5 ng of lipopolysaccharide (LPS) in the left or right
      radiocarpal joint. An epidural catheter was later introduced in the lumbosacral
      space and advanced up to the thoracolumbar level. The treatment started 6 h after
      synovitis induction. Lameness, maximum angle of carpal flexion, heart rate,
      systolic arterial pressure, respiratory rate, temperature, and intestinal
      motility were evaluated before LPS injection (baseline), 6 h after LPS injection
      (time 0), and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after treatments.
      Although the model of synovitis produced clear clinical signs of inflammation,
      the lameness scores in group C were different from the baseline for only up to 12
      h. Both morphine and buprenorphine showed a reduction in the degree of lameness
      starting at 0.5 and 6 h, respectively. Reduced intestinal motility was observed
      at 0.5 h in group M and at 0.5 to 1 h in group B. Epidural morphine was a more
      effective analgesic that lasted for more than 12 h and without side effects. It
      was concluded that morphine would be a valuable analgesic option to alleviate
      joint pain in the thoracic limbs in ponies.

PMID- 21731187
TI  - Effect of reproductive disorders and parity on repeat breeder status and culling
      of dairy cows in Quebec.
AB  - This study quantified the effect of peripartum reproductive disorders and parity
      on repeat breeder status and involuntary culling of dairy cows. Reproductive data
      of 418 383 lactations were taken from a computerized databank of health records
      for dairy cows. A logistic regression model was used with dystocia, retained
      placenta (RP), metritis complex, and parity as fixed effect risk factors and herd
      entered as the random effect. Of the peripartum problems studied, dystocia had
      the greatest effect on future fertility. Dystocia increased the odds of a cow
      being a repeat breeder by 44% [odds ratio (OR): 1.44; confidence interval (CI):
      1.37 to 1.51]. Compared to first-parity cows, cows in second, third, and fourth
      parities had significantly higher odds of being a repeat breeder: 18% (OR: 1.18;
      CI: 1.16 to 1.20); 24% (OR: 1.24; CI: 1.21 to 1.26); and 42% (OR: 1.42; CI: 1.39
      to 1.45), respectively. The odds for second-, third-, or fourth-parity repeat
      breeders being culled were 24% (OR: 1.24; CI: 1.20 to 1.28); 39% (OR: 1.39; CI:
      1.35 to 1.43); and 67% (OR: 1.67; CI: 1.62 to 1.71) respectively, while
      peripartum reproductive problems had less of an effect.

PMID- 21731188
TI  - Experimental transmission of chronic wasting disease (CWD) from elk and white
      tailed deer to fallow deer by intracerebral route: final report.
AB  - Final observations on experimental transmission of chronic wasting disease (CWD)
      from elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus)
      to fallow deer (Dama dama) are reported herein. During the 5-year study, 13 fawns
      were inoculated intracerebrally with CWD-infected brain material from white
      tailed deer (n = 7; Group A) or elk (n = 6; Group B), and 3 other fawns were kept
      as uninoculated controls (Group C). As described previously, 3 CWD-inoculated
      deer were euthanized at 7.6 mo post-inoculation (MPI). None revealed presence of
      abnormal prion protein (PrP(d)) in their tissues. At 24 (Group A) and 26 (Group
      B) MPI, 2 deer were necropsied. Both animals had a small focal accumulation of
      PrP(d) in their midbrains. Between 29 and 37 MPI, 3 other deer (all from Group A)
      were euthanized. The 5 remaining deer became sick and were euthanized between 51
      and 60 MPI (1 from Group A and 4 from Group B). Microscopic lesions of spongiform
      encephalopathy (SE) were observed in only these 5 animals; however, PrP(d) was
      detected in tissues of the central nervous system by immunohistochemistry,
      Western blot, and by commercial rapid test in all animals that survived beyond 24
      MPI. This study demonstrates that intracerebrally inoculated fallow deer not only
      amplify CWD prions, but also develop lesions of spongiform encephalopathy.

PMID- 21731189
TI  - Telemetric measurement of body core temperature in exercising unconditioned
      Labrador retrievers.
AB  - This project evaluated the use of an ingestible temperature sensor to measure
      body core temperature (Tc) in exercising dogs. Twenty-five healthy, unconditioned
      Labrador retrievers participated in an outdoor 3.5-km run, completed in 20 min on
      a level, 400-m grass track. Core temperature was measured continuously with a
      telemetric monitoring system before, during, and after the run. Data were
      successfully collected with no missing data points during the exercise. Core
      temperature elevated in the dogs from 38.7 +/- 0.3 degrees C at pre-exercise to
      40.4 +/- 0.6 degrees C post-exercise. While rectal temperatures are still the
      standard of measurement, telemetric core temperature monitors may offer an easier
      and more comfortable means of sampling core temperature with minimal human and
      mechanical interference with the exercising dog.

PMID- 21731190
TI  - Chemosensory processing in the taste - reward pathway.
AB  - Although the act of eating is voluntary, its initiation depends on several
      factors including its taste and the animal's internal state as related to hunger
      or satiety. These factors together with the food's hedonic value will determine
      whether food will be ingested. The taste of food will depend on the activation of
      receptors located on taste cells but also on the expectation of what it will
      taste like. For these reasons, it is important to investigate, in behaving
      animals, the neural correlates of feeding behavior in the taste-reward pathway.
      Here we review particular coding strategies, present experiments using freely
      licking rodents with chronically implanted arrays of electrodes throughout the
      taste-reward pathway to investigate the changes that occur when animals learn to
      discriminate among tastants and after they are ingested. In summary, we found
      that gustatory processing does not only depend on the input from the oral cavity
      but on expectation, learning, and post-ingestive effects.

PMID- 21731191
TI  - Continual Reassessment and Related Dose-Finding Designs.
AB  - During the last twenty years there have been considerable methodological
      developments in the design and analysis of Phase 1, Phase 2 and Phase 1/2 dose
      finding studies. Many of these developments are related to the continual
      reassessment method (CRM), first introduced by O'Quigley, Pepe and Fisher (1990).
      CRM models have proven themselves to be of practical use and, in this discussion,
      we investigate the basic approach, some connections to other methods, some
      generalizations, as well as further applications of the model. We obtain some new
      results which can provide guidance in practice.

PMID- 21731192
TI  - Pd nanoparticles deposited on poly(lactic acid) grafted carbon nanotubes:
      synthesis, characterization and application in Heck C-C coupling reaction.
AB  - Herein we described the synthesis of a novel f-CNTs-Pd nanocatalyst by covalent
      grafting of poly(lactic acid) (PLA) onto carbon nanotubes (CNTs) and subsequent
      deposition of Pd nanoparticles. Prior to grafting of PLA, CNTs were oxidized with
      a mixture of HNO(3)/H(2)SO(4) and successively activated with thionyl chloride.
      The PLA grafted CNTs (f-CNTs) were then used as platform for in-situ deposition
      of Pd nanoparticles. The formation of f-CNTs-Pd nanocatalyst was analyzed by UV
      vis, FTIR and Raman spectroscopy, powder XRD, energy dispersive spectroscopy and
      thermogravimetric analysis. The morphologies of the nanocatalyst were
      characterized using scanning and transmission electron microscopes. The f-CNTs
      stabilized Pd nanoparticles are found to be more effective in the promotion of
      Heck cross-coupling reaction between aryl halides and n-butyl acrylate. The f
      CNTs-Pd nanocatalyst was regenerated for three cycles of reaction without any
      significant loss in its activity.

PMID- 21731193
TI  - Preventive medication use among persons with limited life expectancy.
AB  - Persons with limited life expectancy (LLE) - less than 1 year - are significant
      consumers of health care, are at increased risk of polypharmacy and adverse drug
      events, and have dynamic health statuses. Therefore, medication use among this
      population must be appropriate and regularly evaluated. The objective of this
      review is to assess the current state of knowledge and clinical practice
      presented in the literature regarding preventive medication use among persons
      with LLE. We searched Medline, Embase, and CINAHL using Medical Subject Headings.
      Broad searches were first conducted using the terms 'terminal care or therapy' or
      'advanced disease' and 'polypharmacy' or 'inappropriate medication' or
      'preventive medicine', followed by more specific searches using the terms
      'statins' or 'anti-hypertensives' or 'bisphosphonates' or 'laxatives' and
      'terminal care'. Frameworks to assess appropriate versus inappropriate
      medications for persons with LLE, and the prevalence of potentially inappropriate
      medication use among this population, are presented. A considerable proportion of
      individuals with a known terminal condition continue to take chronic disease
      preventive medications until death despite questionable benefit. The addition of
      palliative preventive medications is advised. There is an indication that as
      death approaches the shift from a curative to palliative goal of care translates
      into a shift in medication use. This literature review is a first step towards
      improving medication use and decreasing polypharmacy in persons at the end of
      life. There is a need to develop consensus criteria to assess appropriate versus
      inappropriate medication use, specifically for individuals at the end of life.

PMID- 21731195
TI  - Oxidatively Damaged DNA: A Possible Antigenic Stimulus for Cancer Autoantibodies.
AB  - Reactive oxygen species (ROS) are cytotoxic at higher concentration resulting in
      cell death, mutations, chromosomal aberrations or carcinogenesis. In this study
      DNA was modified by singlet oxygen and superoxide anion radicals generated by
      illumination of riboflavin under 365 nm UV-light. The modified DNA induced high
      titre antibodies in experimental animals. In enzyme immunoassay, serum antibodies
      from cancer patients (n = 34) showed a higher recognition of the modified DNA, as
      compared to the native form. This was further confirmed by the gel-shift assay.
      Immune IgG were used as a probe to detect oxidative lesions in the DNA of cancer
      patients. DNA isolated from lymphocytes of cancer patients proved to be an
      appreciable inhibitor of the experimentally induced antibodies against the ROS
      DNA. This indicates the presence of oxidative lesions in the DNA obtained from
      cancer patients. The results show that ROS induced oxidative damage to DNA in
      cancer patients generate neo-epitopes that are alien for the immune system,
      resulting in autoantibody formation.

PMID- 21731194
TI  - Reconvene and reconnect the antioxidant hypothesis in human health and disease.
AB  - The antioxidants are essential molecules in human system but are not miracle
      molecules. They are neither performance enhancers nor can prevent or cure
      diseases when taken in excess. Their supplemental value is debateable. In fact,
      many high quality clinical trials on antioxidant supplement have shown no effect
      or adverse outcomes ranging from morbidity to all cause mortality. Several
      Chochrane Meta-analysis and Markov Model techniques, which are presently best
      available statistical models to derive conclusive answers for comparing large
      number of trials, support these claims. Nevertheless none of these statistical
      techniques are flawless. Hence, more efforts are needed to develop perfect
      statistical model to analyze the pooled data and further double blind, placebo
      controlled interventional clinical trials, which are gold standard, should be
      implicitly conducted to get explicit answers. Superoxide dismutase (SOD),
      glutathione peroxidase and catalase are termed as primary antioxidants as these
      scavenge superoxide anion and hydrogen peroxide. All these three enzymes are
      inducible enzymes, thereby inherently meaning that body increases or decreases
      their activity as per requirement. Hence there is no need to attempt to
      manipulate their activity nor have such efforts been clinically useful. SOD
      administration has been tried in some conditions especially in cancer and
      myocardial infarction but has largely failed, probably because SOD is a large
      molecule and can not cross cell membrane. The dietary antioxidants, including
      nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme
      antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen
      species (RNS) within physiological limits. Since body is able to regulate its own
      requirements of enzyme antioxidants, the diet must provide adequate quantity of
      non-enzymic antioxidants to meet the normal requirements and provide protection
      in exigent condition. So far, there is no evidence that human tissues ever
      experience the torrent of reactive species and that in chronic conditions with
      mildly enhanced generation of reactive species, the body can meet them squarely
      if antioxidants defense system in tissues is biochemically optimized. We are not
      yet certain about optimal levels of antioxidants in tissues. Two ways have been
      used to assess them: first by dietary intake and second by measuring plasma
      levels. Lately determination of plasma/serum level of antioxidants is considered
      better index for diagnostic and prognostic purposes. The recommended levels for
      vitamin A, E and C and beta carotene are 2.2-2.8 MUmol/l; 27.5-30 MUmol/l; 40-50
      MUmol/l and 0.4-0.5 MUmol/l, respectively. The requirement and recommended blood
      levels of other dietary antioxidants are not established. The resolved issues are
      (1) essential to scavenge excess of radical species (2) participants in redox
      homeostasis (3) selective antioxidants activity against radical species (4) there
      is no universal antioxidant and 5) therapeutic value in case of deficiency. The
      overarching issues are (1) therapeutic value as adjuvant therapy in management of
      diseases (2) supplemental value in developing population (3) selective
      interactivity of antioxidant in different tissues and on different substrates (4)
      quantitative contribution in redox balance (5) mechanisms of adverse action on
      excess supplementation (6) advantages and disadvantages of prooxidant behavior of
      antioxidants (7) behavior in cohorts with polymorphic differences (8) interaction
      and intervention in radiotherapy, diabetes and diabetic complications and
      cardiovascular diseases (9) preventive behavior in neurological disorders (10)
      benefits of non-nutrient dietary antioxidants (11) markers to assess optimized
      antioxidants status (12) assessment of benefits of supplementation in alcoholics
      and heavy smokers. The unresolved and intriguing issues are (1) many compounds
      such as vitamin A and many others possessing both antioxidant and non-antioxidant
      properties contribute to both the activities in vivo or exclusively only to non
      antioxidant activity and (2) since human tissues do not experience the surge of
      FR, whether there is any need to develop stronger synthetic antioxidants.
      Theoretically such antioxidants may do more harm than good.

PMID- 21731196
TI  - Matrix metalloproteinases and their inhibitors: correlation with invasion and
      metastasis in oral cancer.
AB  - Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis
      of various malignancies. The study evaluated a comprehensive profile of MMP-2 and
      MMP-9 and their inhibitors, tissue inhibitor of metalloproteinases-2 (TIMP-2) and
      tissue inhibitor of metalloproteinases-1 (TIMP-1), respectively in 50 controls
      and 75 patients with oral squamous cell carcinoma (OSCC). Blood samples from
      controls and patients as well as malignant and adjacent normal tissues from the
      patients were collected. The study examined pro, active and total forms of MMP-2
      and MMP-9 using zymography. Enzyme-linked immunoassay (ELISA) and reverse
      transcription polymerase chain reaction were carried out to evaluate protein
      levels and mRNA expression; respectively, for the MMPs and TIMPs. Plasma pro,
      active and total MMP-2, MMP-9 as well as TIMP-1 and TIMP-2 levels were
      significantly higher in oral cancer patients as compared to the controls. mRNA
      expression of the MMPs and TIMPs was significantly higher in malignant tissues as
      compared to adjacent normal tissues. A significant positive correlation was
      observed between levels of proMMP-9 and active MMP-9 with differentiation, stage
      and infiltration. ProMMP-2 and active MMP-2 exhibited significant positive
      correlation with differentiation and lymph node involvement. The multivariate
      analysis of ELISA results revealed a significant positive correlation between MMP
      2, TIMP-1 and TIMP-2 levels with lymph node involvement, stage and
      differentiation. The receiver operating characteristic curve (ROC) analysis
      showed that the levels of MMPs and TIMPs have significant discriminatory efficacy
      to differentiate between controls and patients. The results indicate that MMP-2,
      MMP-9, TIMP-1 and TIMP-2 have significant clinical usefulness for oral cancer
      patients. Zymographic analysis is a simple, cost effective, rapid and sensitive
      alternative assay.

PMID- 21731197
TI  - Polymorphisms of CYP1A1, GSTM1 and GSTT1 Loci as the Genetic Predispositions of
      Oral Cancers and Other Oral Pathologies: Tobacco and Alcohol as Risk Modifiers.
AB  - Polycyclic aromatic hydrocarbons of tobacco require activation by phase I
      enzymes, such as cytochrome-P4501A1 (CYP1A1) to become an ultimate carcinogen,
      which are subjected to detoxification by phase II enzymes, especially glutathione
      S-transferases (GSTs). A study was designed to find whether genetic
      predisposition are risk modifiers of oral pathologies. The study included 102
      cases with Oral Cancers (OCs), 68 cases with nonmalignant pathologies, 100 cases
      as control group. GSTM1 null genotype was associated with increased risk of OCs
      but not with benign pathologies. Deleted GSTT1 was associated with all
      pathologies. Both m1m2 and m2m2 polymorphisms of CYP1A1 were associated with oral
      pathologies.

PMID- 21731198
TI  - Leucine125Valine (Leu125Val) Gene Polymorphism of Platelet Endothelial Cell
      Adhesion Molecule-1 (PECAM-1) and Myocardial Infarction in Indian Population.
AB  - Platelet-endothelial cell adhesion molecule-1 (PECAM-1) has role in
      atherosclerotic plaque development as well as in thrombosis leading to myocardial
      infarction (MI). Present study was aimed to analyse the association of PECAM-1
      Leu125Val gene polymorphism with MI in Indian population. Subjects included
      healthy individuals as control (N = 116) and MI patients (N = 100) divided into
      two groups; MI patients at presentation of the acute event (MI-Group-1, N = 46)
      and patients with recent event of MI stabilized with treatment 4.5 days from
      their symptoms (MI-Group-2, N = 54). The difference in the distribution of
      Leu125Val genotype frequencies of controls and patients did not reach statistical
      significance. However Leu allele frequency (0.57) was more associated with MI
      patients as compared to control (0.504). sPECAM-1 levels were significantly
      elevated in patients at acute event of MI (MI-Group-1) by 44.1% (P = 0.009) as
      compared to controls and by 95.2% (P = 0.001) as compared to stabilized MI
      patients (MI-Group-2).

PMID- 21731199
TI  - Garlic Oil and Vitamin E Prevent the Adverse Effects of Lead Acetate and Ethanol
      Separately as well as in Combination in the Drinking Water of Rats.
AB  - Daily feeding of drinking water containing lead acetate (160 mg/l) or 10% alcohol
      by volume or a combination of both to rats for a month produced certain
      deleterious effects through oxidative stress. Both heavy metal lead and alcohol
      are capable of doing such damages. The deleterious alterations observed were in
      the parameters of blood, serum and tissues, viz; Hb, Pb, proteins, lipids, lipid
      per oxidation, Vitamins C and E levels and enzyme activities of AST, ALT, and
      catalase. Simultaneous feeding of either of the two antioxidants garlic oil (GO)
      and vitamin E at equal doses of 100 mg/kg/day, to the rats counteracted the
      deleterious effects of the above two chemicals significantly. The maximum damage
      was brought about by feeding of drinking water containing both lead acetate and
      alcohol. The protective effects of GO and Vitamin E were not significantly
      different. The mechanism of actions of the Vitamin E and GO is probably due to
      their efficiency as detoxifying agents and antioxidants, to scavenging free
      radicals as well as an independent action of GO on the removal of lead salt as
      lead sulfide.

PMID- 21731200
TI  - Acetylation pharmacogenetics and renal function in diabetes mellitus patients.
AB  - Activities of human hepatic drug metabolizing enzymes N-acetyl transferase (NATS)
      had earlier been recognized as a cause of inter-individual variation in the
      metabolism of drugs. Therefore acetylation of many drugs in human exhibit genetic
      polymorphism. The aim of the study was to investigate if acetylator status
      predispose diabetic mellitus patients more to the complications of renal disease,
      One hundred and twenty (120) diabetics consisting of (50) Type 1 (T(1)) and 70
      Type 2 (T(2)) diabetes mellitus patients and 100 healthy individuals as controls
      were classified as slow or rapid acetylator using sulphamethazine (SMZ) as an in
      vivo probe. The percentage acetylation, recovery of SMZ, creatinine clearance and
      presence of urinary albumin were determined. A significant difference (P < 0.05)
      was observed in the percentage of SMZ acetylated between slow and rapid
      acetylators in control, T(1) and T(2) subjects. The ratios of slow to rapid
      acetylators for T(1), T(2) and control subjects were 1:4, 3:2 and 2:3
      respectively. No significant differences were observed in the percentage of SMZ
      recovered in the urine of slow and rapid acetylators that are diabetics. The
      difference in creatinine clearance of slow and rapid acetylators in T(1) and T(2)
      were significant (P < 0.05). 29% out of 120 (24.2%) diabetics (T(1) and T(2))
      exhibited albuminuria out of which 25 (86.2%) had slow acetylator status. These
      findings suggest that slow acetylator status in diabetes mellitus could be a
      predisposing factor in the development of renal complications. This underscores
      the need for a rapid pharmacogenetic testing and therapeutic drug monitoring in
      such patients. However this inference could be further validated with a larger
      sample size.

PMID- 21731201
TI  - A community based study of the relationship between homocysteine and some of the
      life style factors.
AB  - Till date no community based data on plasma homocysteine is available in North
      Eastern Region. Hence, the present study was conducted to analyze and correlate
      the plasma homocysteine level with some life style factors like diet, alcohol
      intake, smoking habit and body weight, in a cross-section of population. 12 h
      fasting samples of 970 apparently healthy, Assamese population of both genders in
      the age group of 35-86 years, mostly from the urban area of Assam were tested for
      plasma total homocysteine level over a period of 3 years. Out of 970 volunteers,
      hyperhomocysteinemia was detected in 533 (55%) individuals with a mean value of
      18.41 MUmol/l. Of that hyperhomocysteinemia, 89.1% were in the range of
      moderately high and rest 10.9% were intermediate high. Another finding was that
      males had a tendency towards greater value (mean = 20.36 MUmol/l) than females
      (mean = 16.37 MUmol/l). It was observed that the relationship of homocysteine
      levels to gender and some of the life style factors were also significant.

PMID- 21731202
TI  - Protective Role of l-Arginine Against Free-Radical Mediated Oxidative Damage in
      Patients with Unstable Angina.
AB  - Unstable angina is a critical condition of heart resulting from narrowing of
      vessels supplying blood to heart. Ischemia of the myocardium leads to oxidative
      stress and severe tissue damage. The objective of the present study was to
      determine the effect of l-arginine administration on the oxidant-antioxidant
      homeostasis which otherwise gets imbalanced in patients with cardiovascular
      diseases. The results obtained, show improvement in the oxidant-antioxidant
      levels of the subjects upon incorporation of l-arginine. Our findings suggest
      that supplementation of l-arginine along with regular anti-anginal therapy may be
      beneficial to the patients of unstable angina.

PMID- 21731203
TI  - Antioxidant Activities of Hydroalcoholic Extract of Ocimum sanctum Against
      Cadmium Induced Toxicity in Rats.
AB  - The present study was undertaken to analyze the antioxidant (both enzymic and
      nonenzymic) activities of leaves of Ocimum sanctum hydroalcoholic extract against
      cadmium induced damage in albino rats. Oral administration of cadmium as CdCl(2)
      (6.0 mg/kg body weight) led to significant elevation of lipid peroxidation (LPO)
      levels and significantly decreased Superoxide Dismutase (SOD), Catalase (CAT),
      Glutathione Peroxidase (GPx), Reduced Glutathione (GSH) and Vitamin C (Ascorbate)
      levels. Administration of Ocimum sanctum extract (100 mg/kg body weight, po) and
      (200 mg/kg body weight, po) before and after cadmium intoxication showed a
      significant decrease in LPO levels and significant increase in SOD, CAT, GPx, GSH
      and Ascorbate levels. The results suggest that oral administration of Ocimum
      sanctum extract provides significant protection against cadmium induced toxicity
      in Wistar albino rats.

PMID- 21731204
TI  - Does chewing coca leaves influence physiology at high altitude?
AB  - Andean Indians have used coca leaves (Erythroxylon coca and related species) for
      centuries to enhance physical performance. The benefits and disadvantages of
      using coca leaf have been a subject of many political debates. The aim of this
      study was to investigate the effects of chewing coca leaves on biochemical and
      physiological parameters. Cutaneous microdialysis catheters were used to estimate
      systemic biochemical changes. We subjected 10 healthy adult males (local
      residents) in Cajamarca (Peru, altitude 2700 m) to a standardised exercise
      routine on a stationary cycle ergometer. The blood pressure, oxygen saturation
      (digital), pulse, VO2 max and ECG (Holter monitor) were recorded before the
      exercise. Cutaneous microdialysis catheters were introduced in the forearm. The
      subjects were given to chew 8 g of coca leaves with a small amount of lime. They
      were then placed on the cycle ergometer for 20 min. Blood pressure, oxygen
      saturation, pulse, ECG and VO2 max were recorded. Pyruvate, glucose, lactate,
      glycerol and glutamate levels were estimated. Oxygen saturation, blood pressure,
      and pulse rate did not show any significant changes between the two groups.
      Glucose levels showed hyperglycaemic response. Glycerol, Lactate and Pyruvate
      increased. Glutamate remained unchanged. Similar changes were not seen in the
      controls. These results suggest that coca leaves have blocked the glycolytic
      pathway of glucose oxidation resulting in accumulation of glucose and pyruvate.
      The energy requirement for exercise is being met with beta-oxidation of fatty
      acids. The glycerol released was also getting accumulated since its pathway for
      oxidation was blocked. These experimental findings suggest that chewing coca
      leaves is beneficial during exercise and that the effects are felt over a
      prolonged period of sustained physical activity.

PMID- 21731205
TI  - Rapid Detection of Mutation in RRDR of rpo B Gene for Rifampicin Resistance in
      MDR-Pulmonary Tuberculosis by DNA Sequencing.
AB  - To detect the site of mutation in RRDR of rpo B gene for rifampicin resistance in
      MDR-TB by DNA sequencing. 50 MDR-TB patients were enrolled in our study after
      informed written consent. Mycobacterial DNA was extracted from sputum samples by
      Universal Sample Processing (USP) method and RRDR of rpo B gene was amplified by
      PCR using primers RP4T and RP8T and then sequenced by automated DNA sequencing.
      The nucleotide sequences of RRDR of rpo B gene were compared with the reference
      sequence. We observed three different types of mutation in the RRDR of rpo B
      gene. The frequency of mutation in codon 531 (TCG -> TTG), 526 (CAC -> TAC) and
      516 (GAC -> GTC) are 60, 26.6 and 6.6% respectively. Of the total cases studied,
      6.6% cases, although resistant to rifampicin, did not show any mutation in the
      RRDR of rpo B gene. Codon 531 (TCG -> TTG) is the most common site of mutation in
      RRDR of rpo B gene for rifampicin resistance in MDR-pulmonary tuberculosis
      followed by codon 526 (CAC -> TAC) and codon 516 (GAC -> GTC). ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12291
      010-0065-3) contains supplementary material, which is available to authorized
      users.

PMID- 21731206
TI  - Efficient Expression of Bioactive Human Leptin in Escherichia coli in Soluble
      Fusion Form.
AB  - Leptin, a 16 kDa nonglycosylated hormone, is produced by mature adipocytes and
      functions primarily in the hypothalamus to reduce food intake and body weight. To
      explore a new approach for high-level expression of human Leptin in Escherichia
      coli, the human Leptin gene, synthesized according to the published sequence, was
      cloned into the vector pET32a to construct a fusion expression plasmid: Trx
      Leptin/pET32a. Our data showed that more than 40% of the fusion protein Trx
      Leptin was expressed in soluble form. After purified by Ni-IDA affinity
      chromatography, cleaved by enterokinase and applied Ni-IDA affinity
      chromatography again, purified Leptin with homogeneity over 96% was achieved. The
      bio-functional experiments of purified Leptin showed a significant reduction in
      food intake and body weight of female mice treated with Leptin by comparing with
      control mice, and it indicated that the purified Leptin has full biological
      activity. In addition, our expression system was a very low-cost and efficient
      prokaryotic expression system. So taken together, our results demonstrated that
      our expression system of bio-active Leptin provided a new method for producing
      Leptin in big scale and would be widely applied in commercial Leptin producing
      industries.

PMID- 21731207
TI  - Three cases of lead toxicity associated with consumption of ayurvedic medicines.
AB  - Ayurveda is a traditional form of medicine used by majority of the Indians. Here
      we report three cases of lead toxicity, following intake of Ayurvedic medicines.
      Three patients presented with blood lead levels (BLLs) of 122.4, 115 and 42.8
      MUg/dl respectively at the time of hospitalization. The first case was chelated
      with D- penicillamine, the second with calcium disodium ethylene diamino tetra
      acetate (EDTA) and the third with environmental intervention and education.
      Associated Ayurvedic products were collected from patients and analyzed for
      metallic concentration. Cessation of Ayurvedic medication along with chelation,
      nutritional intervention and education, reduced the BLL to 27.4 MUg/dl in the
      first case after 1 year, 21.1 MUg/dl after 9 months in the second and 18.2 MUg/dl
      after 6 months in the third case.

PMID- 21731208
TI  - To listen is to be...

PMID- 21731209
TI  - Epidemiological review of gastric cancer in India.
AB  - Stomach cancer is the one of the leading cause of cancer in southern region of
      India. Its incidence is decreasing worldwide yet on global scale stomach cancer
      remains one of the most common causes of cancer death. Etiology of gastric cancer
      includes Helicobacter pylori infection, diet and lifestyle, tobacco, alcohol and
      genetic susceptibility. In this review, we tried to find the contribution of
      Indian scientist in understanding the descriptive and observational epidemiology
      of stomach cancer. PubMed was used as a search platform using key words such as
      "stomach cancer, treatment, clinical characteristics, stomach cancer outcome,
      epidemiology, etiological factor and their corresponding Mesh terms were used in
      combination with Boolean operators OR, AND". Most of the reported studies on
      gastric cancer from India are case report or case series and few are case-control
      studies. Indian studies on this topic are limited and have observed H. pylori
      infection, salted tea, pickled food, rice intake, spicy food, soda (additive of
      food), tobacco and alcohol as risk factors for gastric cancer. More research is
      required to understand the etiology, develop suitable screening test, to
      demarcate high-risk population and to develop and evaluate the effect of primary
      prevention programs.

PMID- 21731210
TI  - Gastric cancer in India.
AB  - The incidence of gastric cancer in India is low compared to developed countries,
      though there are certain geographical areas (Southern part and northeastern
      states of country) where the incidence is comparable to high-incidence areas of
      world. Despite the large number of patients being treated for gastric cancer,
      there are not sufficient publications discussing associated risk factors and
      outcomes in these patients. This article discusses relevant Indian
      epidemiological and clinical studies about gastric cancers. This article also
      highlights the gap in publication from India and developed countries regarding
      gastric cancer and stresses on collaborative efforts of the Indian scientific
      community to conduct epidemiological, pathological, and clinical studies to have
      a new standard of care for Indian patients.

PMID- 21731211
TI  - Evolving role of high dose stem cell therapy in multiple myeloma.
AB  - Conventional chemotherapy has been used in the treatment of multiple myeloma.
      However the development of autologous stem cell transplant represented a major
      advance in its therapy. Complete response (CR) rates to the tune of 40-45% were
      seen and this translated into improvements in progression-free survival and also
      overall survival in some studies. As a result the autologous stem cell
      transplants (ASCT) is the standard of care in eligible patients and can be
      carried out with low treatment-related mortality. Allogenic transplant carries
      the potential for cure but the high mortality associated with the myeloablative
      transplant has made it unpopular. Reduced Intensity Stem Cell Transplants (RIST)
      have been tried with varying success but with a high degree of morbidity as
      compared to the ASCT. Introduction of newer agents like thalidomide,
      lenalidomide, bortezomib and liposomal doxorubicin into the induction regimens
      has resulted in higher CR and very good partial response rates (VGPR) as well as
      improvement in ease of administration. These drugs have also proved useful in
      patients with adverse cytogenetics. Recent trials suggest that this has
      translated into improvements in response rates post-ASCT. There is a suggestion
      that patients achieving CR/nCR or VGPR after induction therapy should be placed
      on maintenance and ASCT then could be used as a treatment strategy at relapse.
      All these trends however await confirmation from further trials. Tandem
      transplants have been used to augment the results obtained with ASCT and have
      demonstrated their utility in patients who achieved only a partial response or
      stable disease in response to the first transplant as well as patients with
      adverse cytogenetics. Incorporation of bortezomib along with melphalan into the
      conditioning regimen has also been tried. RIST following ASCT has been tried with
      varying success but does not offer any major advantage over ASCT and is
      associated with higher morbidity. It is hoped that recent advances in therapy
      will contribute greatly to improved survival.

PMID- 21731212
TI  - Role of glutathione-s-transferase and CYP1A1*2A polymorphisms in the therapy
      outcome of south Indian acute lymphoblastic leukemia patients.
AB  - BACKGROUND: Polymorphisms in the drug-metabolizing enzymes are found to be
      associated with the inter-individual variation in response to a particular drug.
      Glutathione S-transferases (GSTs) are involved in the metabolism of several
      anticancer drugs, including alkylating agents, anthracyclines, and
      cyclophosphamides. AIM: The present study is aimed to examine the association of
      GST and CYP1A1*2A polymorphisms in the susceptibility to acute lymphoblastic
      leukemia (ALL) and the prognostic significance. MATERIALS AND METHODS: A total of
      92 immunophenotyped patients and 150 cord blood controls were genotyped by PCR
      for GSTM1 and GSTT1, RQ-PCR allelic discrimination assay for GSTP1 and PCR-RFLP
      for CYP1A1*2A polymorphism. RESULTS: We have previously reported the significant
      association of GSTM1 (null) and combined GSTP1 {(Ile/Val)/ (Val/Val)} /GSTM1
      (null) genotype with the susceptibility to ALL. No significant association was
      observed with GSTT1 (P=0.75) and CYP1A1*2A (P=0.61 for +/- and P=0.86 for -/-
      respectively) in the susceptibility to ALL. Survival analysis was performed in 50
      of the 92 patients who were followed for three years. Kaplan-Meier survival
      analysis for three years showed significant lower event-free survival in patients
      harboring GSTP1 (Ile/Val) and GSTP1 (Val/Val) (P=0.038 and 0.0001, respectively)
      genotype. Cox regression analysis revealed GSTP1 as an independent prognostic
      marker with 6-fold higher risk with Val/Val genotype (P=0.003). CONCLUSIONS: Our
      results show that GSTP1 (Ile/Val) polymorphism has a role in the susceptibility
      to ALL and also influence treatment outcome.

PMID- 21731213
TI  - Childhood cancer in developing society: A roadmap of health care.
AB  - BACKGROUND: We assessed referral patterns of children with hematological
      malignancies (HM) in North India. MATERIALS AND METHODS: The parents/guardians
      were interviewed at presentation, in the period between October 2001 and November
      2002. Patient delay (symptom-contact), health system delay (contact-diagnosis),
      total delay (symptom-diagnosis), and number of contacts were compared between
      high- and standard-risk disease group. RESULTS: Of the 79 children (55 boys;
      69.6%) with HM, 47 (59.5%) had Acute Lymphoblastic Leukemia (ALL). Forty-four
      children had high-risk disease. The patient, system and total delay were a median
      of 2 days (with Interquartile range IQR of 1-6), 37 days (IQR 13-55), and 38 days
      (IQR 15-60) respectively. Majority of patients (64/79; 81%) went to private
      sector (non governmental health care providers) for health care. Number of
      contacts, which was the most significant, correlate with system delay.
      CONCLUSIONS: Sensitizing the private sector practitioners about cancer in
      symptomatic children (pallor, bleeding, fever) may be effective.

PMID- 21731214
TI  - The relationship between serum lipid levels and the risk of oral cancer.
AB  - BACKGROUND: Lipids are the major cell membrane components essential for various
      biological functions including cell growth and division for the maintenance of
      cell integrity of normal and malignant tissues. The changes in lipid profile have
      long been associated with cancer. Hypocholesterolemia has been observed in
      patients with cancers of various organs. Therefore, a causative relationship
      might exist between plasma lipid levels and oral cancer patients. AIM: The
      objective of this study was to investigate the alterations and clinical
      significance of plasma lipid profiles in untreated head and neck cancer patients.
      MATERIALS AND METHODS: A total of 30 subjects (25 oral cancer patients and 5
      controls) were included. Fasting blood lipid profile including cholesterol (C),
      triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL)
      and very low density lipoprotein (VLDL) were evaluated using spectrophotometric
      kits, with CHOD PAP technique. The values were then statistically analyzed using
      analysis of variance (ANOVA) and post hoc methods. RESULTS: The levels of total
      lipids, cholesterol and HDL were significantly lower in oral cancer patients as
      compared to controls, but LDL and VLDL values were not significant. CONCLUSION:
      An inverse relationship was found between the lipid levels and the occurrence of
      oral cancer. Hence, the lower plasma lipid status may be a useful indicator to
      detect the initial changes seen in neoplastic process.

PMID- 21731215
TI  - Carnitine levels and cardiac functions in children with solid malignancies
      receiving doxorubicin therapy.
AB  - AIM: Previous studies demonstrated l-carnitine decreasing doxorubicin-induced
      cardiotoxicity. Our objectives were to study carnitine levels and cardiac
      functions in children treated with doxorubicin and the effect of short-term l
      carnitine supplements. MATERIALS AND METHODS: Serial carnitine levels and cardiac
      functions were obtained in children with newly diagnosed solid malignancies
      before doxorubicin, after cumulative doses of >=150 mg/m(2) and >=300 mg/m(2),
      respectively. Oral l-carnitine 100 mg/kg/day for 3 days were given to the
      children treated with doxorubicin at cumulative doses of >=150 mg/m(2) and >=300
      mg/m(2). Carnitine levels and cardiac functions were also obtained in those
      children before and after short-term oral l-carnitine at each cumulative dose of
      doxorubicin. RESULTS: Five children (3 females), median age of 9.1 years (range
      1.5-13 years) with newly diagnosed solid malignancies were enrolled in the study.
      Free carnitine (FC) tended to decrease while acyl-carnitine (AC) increased making
      AC/FC ratio increased after cumulative dose of >=150 and >=300 mg/m(2) but the
      statistics was not significant. Left ventricular (LV) systolic function was not
      significantly changed. Interestingly, LV global function (LV myocardial
      performance index) was significantly increased after 150 mg/m(2) (median 0.39,
      0.27-0.51) and 300 mg/(2) (median 0.46, 0.27-0.50) when compared to baseline
      (median 0.28, 0.14-0.48) (P=0.05). Carnitine levels and cardiac functions were
      not significantly changed after oral l-carnitine supplement at cumulative dose of
      >=150 mg/m(2) (n=6) and >=300 mg/m(2) (n=9). CONCLUSIONS: Carnitine levels tended
      to decrease after doxorubicin treatment. LV global dysfunction was documented
      early after doxorubicin. However, short-term l-carnitine supplement did not
      improve cardiac function.

PMID- 21731216
TI  - Abiraterone acetate, an inhibitor of adrenal androgen synthesis in "hormone
      refractory prostate cancer".

PMID- 21731217
TI  - Transilluminating testicular mass.
AB  - Testicular tumor in prepubertal age group is uncommon. Most of the testicular
      tumors are benign in this age group and present as painless, hard testicular
      mass. We present a case where a 7 year male child presented to us with painless
      scrotal swelling, which was cystic and transilluminating, clinically mimicking as
      hydrocele. On ultrasonography, the mass was solid. Orchidectomy was performed and
      histopathology revealed mature cystic teratoma.

PMID- 21731218
TI  - Extranodal testicular anaplastic versus plasmablastic plasma cell tumor: A rare
      case with diagnostic dilemma in a developing country.
AB  - Primary testicular plasmacytoma is rare, especially when occurring in the absence
      of a previous or concurrent diagnosis of multiple myeloma. An 84-year-old
      gentleman was admitted with complaints of swelling over the right side of scrotum
      for the past 2 months. Local examination revealed a 10*15 cm tense and tender
      swelling involving the right scrotum. Therefore, high orchidectomy with excision
      of hemiscrotum was done. The histopathology revealed testicular plasmacytoma,
      which was positive for CD 138.

PMID- 21731219
TI  - Shorter course of trastuzumab: Caveat emptor.

PMID- 21731220
TI  - Molecular imaging-challenges, opportunities and caveats.

PMID- 21731221
TI  - Consideration of the radiation dose delivered away from the treatment field to
      patients in radiotherapy.
AB  - Radiation delivery to cancer patients for radiotherapy is invariably accompanied
      by unwanted radiation to other parts of the patient's body. Traditionally,
      considerable effort has been made to calculate and measure the radiation dose to
      the target as well as to nearby critical structures. Only recently has attention
      been focused also on the relatively low doses that exist far from the primary
      radiation beams. In several clinical scenarios, such doses have been associated
      with cardiac toxicity as well as an increased risk of secondary cancer induction.
      Out-of-field dose is a result of leakage and scatter and generally difficult to
      predict accurately. The present review aims to present existing data, from
      measurements and calculations, and discuss its implications for radiotherapy.

PMID- 21731222
TI  - Dosimetric effect of multileaf collimator leaf width in intensity-modulated
      radiotherapy delivery techniques for small- and large-volume targets.
AB  - The purpose of this study was to evaluate the dosimetric effect of the leaf width
      of a multileaf collimator (MLC) in intensity-modulated radiotherapy (IMRT)
      delivery techniques for small- and large-volume targets. We retrospectively
      selected previously treated 5 intracranial and 5 head-neck patients for this
      study to represent small- (range, 18.37-72.75 cc; mean, 42.99 cc) and large
      volume (range, 312.31-472.84 cc; mean, 361.14 cc) targets. A 6-MV photon beam
      data was configured for Brianlab m3 (3 mm), Varian Millennium 120 (5 mm) and
      Millennium 80 (10 mm) MLCs in the Eclipse treatment-planning system. Sliding
      window and step-shoot IMRT plans were generated for intracranial patients using
      all the above-mentioned MLCs; but due to the field size limitation of Brainlab
      MLC, we used only 5-mm and 10-mm MLCs in the head-and-neck patients. Target
      conformity, dose to the critical organs and dose to normal tissues were recorded
      and evaluated. Although the 3-mm MLC resulted in better target conformity (mean
      difference of 7.7% over 5-mm MLC and 12.7% over 10-mm MLC) over other MLCs for
      small-volume targets, it increased the total monitor units of the plans. No
      appreciable differences in terms of target conformity, organ at risk and normal
      tissue sparing were observed between the 5-mm and 10-mm MLCs for large-volume
      targets. The effect of MLC leaf width was not quantifiably different in sliding
      window and step and shoot techniques. In addition, we observed that there was no
      additional benefit to the sliding-window (SW) technique when compared to the step
      shoot (SS) technique as a result of reduction of MLC leaf width.

PMID- 21731223
TI  - Feasibility of deformation-independent tumor-tracking radiotherapy during
      respiration.
AB  - To evaluate the feasibility of tumor-tracking radiotherapy that does not consider
      tumor deformation during respiration. Four-dimensional computed tomography (4D
      CT) data, which considers 10 phases of the respiration cycle, were acquired in 4
      patients with lung cancer and 4 patients with liver cancer. Initial treatment
      plans were established at the end of the inhalation phase (phase 1). As a
      simulation of deformation-free tumor-tracking radiotherapy, the beam center of
      the initial plan was moved to the tumor center for all other phases, and the
      tumor shape acquired from phase 1 was used for all 10 phases. The feasibility of
      this method was analyzed based on assessment of equivalent uniform dose (EUD),
      homogeneity index (HI) and coverage index (COV). In photon radiation treatment,
      movement-induced dose reduction was not particularly significant, with 0.5%,
      17.3% and 2.8% average variation in EUD, HI and COV, respectively. In proton
      radiation treatment, movement-induced dose reduction was more significant, with
      0.3%, 40.5% and 2.2% average variation in EUD, HI and COV, respectively. Proton
      treatment is more sensitive to tumor movement than is photon treatment, and that
      it is reasonable to disregard tumor deformation during photon therapy employing
      tumor-tracking radiotherapy.

PMID- 21731224
TI  - A hybrid algorithm for instant optimization of beam weights in anatomy-based
      intensity modulated radiotherapy: A performance evaluation study.
AB  - The study aims to introduce a hybrid optimization algorithm for anatomy-based
      intensity modulated radiotherapy (AB-IMRT). Our proposal is that by integrating
      an exact optimization algorithm with a heuristic optimization algorithm, the
      advantages of both the algorithms can be combined, which will lead to an
      efficient global optimizer solving the problem at a very fast rate. Our hybrid
      approach combines Gaussian elimination algorithm (exact optimizer) with fast
      simulated annealing algorithm (a heuristic global optimizer) for the optimization
      of beam weights in AB-IMRT. The algorithm has been implemented using MATLAB
      software. The optimization efficiency of the hybrid algorithm is clarified by (i)
      analysis of the numerical characteristics of the algorithm and (ii) analysis of
      the clinical capabilities of the algorithm. The numerical and clinical
      characteristics of the hybrid algorithm are compared with Gaussian elimination
      method (GEM) and fast simulated annealing (FSA). The numerical characteristics
      include convergence, consistency, number of iterations and overall optimization
      speed, which were analyzed for the respective cases of 8 patients. The clinical
      capabilities of the hybrid algorithm are demonstrated in cases of (a) prostate
      and (b) brain. The analyses reveal that (i) the convergence speed of the hybrid
      algorithm is approximately three times higher than that of FSA algorithm; (ii)
      the convergence (percentage reduction in the cost function) in hybrid algorithm
      is about 20% improved as compared to that in GEM algorithm; (iii) the hybrid
      algorithm is capable of producing relatively better treatment plans in terms of
      Conformity Index (CI) [~ 2% - 5% improvement] and Homogeneity Index (HI) [~ 4% -
      10% improvement] as compared to GEM and FSA algorithms; (iv) the sparing of
      organs at risk in hybrid algorithm-based plans is better than that in GEM-based
      plans and comparable to that in FSA-based plans; and (v) the beam weights
      resulting from the hybrid algorithm are about 20% smoother than those obtained in
      GEM and FSA algorithms. In summary, the study demonstrates that hybrid algorithms
      can be effectively used for fast optimization of beam weights in AB-IMRT.

PMID- 21731225
TI  - An overview of radioactive waste disposal procedures of a nuclear medicine
      department.
AB  - Radioactive wastes from hospitals form one of the various types of urban wastes,
      which are managed in developed countries in a safe and organized way. In
      countries where growth of nuclear medicine services are envisaged,
      implementations of existing regulatory policies and guidelines in hospitals in
      terms of handling of radioactive materials used in the treatment of patients need
      a good model. To address this issue, a brief description of the methods is
      presented. A designed prototype waste storage trolley is found to be of great
      help in decaying the I-131 solid wastes from wards before releasing to waste
      treatment plant of the city. Two delay tanks with collection time of about 2
      months and delay time of 2 months alternately result in 6 releases of urine
      toilet effluents to the sewage treatment plant (STP) of the hospital annually.
      Samples of effluents collected at releasing time documented radioactive releases
      of I-131 much below recommended levels of bi-monthly release. External counting
      of samples showed good statistical correlation with calculated values. An
      overview of safe procedures for radioactive waste disposal is presented.

PMID- 21731226
TI  - Isoeffect calculations with the linear quadratic and its extensions: An
      examination of model-dependent estimates at doses relevant to hypofractionation.
AB  - The linear quadratic is the standard model for calculating isoeffects in the
      range of conventional dose per fraction. However, the use of hypofractionation
      and stereotactic body radiation therapy can call for isoeffect calculations for
      large doses per fraction. The purpose of this work is to investigate the linear
      quadratic at large doses per fraction. The linear quadratic is compared to models
      that incorporate effects such as dose protraction, whose purpose is to extend the
      useful range of the linear quadratic to larger doses. The linear quadratic and
      extended linear quadratic models are fit to 4 data sets. The model-predicted
      isoeffects for these data sets are calculated. It is found that the linear
      quadratic and extended linear quadratic predict different isoeffect curves for
      certain data sets. However, for these data sets, by appropriate selection of a
      alpha/beta ratio, the linear quadratic can well approximate the extended linear
      quadratic models. In particular, it is found that a alpha/beta ratio of 0.5 well
      approximates the extended linear quadratic isoeffect curve for 2 prostate cell
      lines for conventional and moderate doses per fraction.

PMID- 21731227
TI  - Testing of a treatment planning system with beam data from IAEA TECDOC 1540.
AB  - Quality assurance of external-beam treatment-planning systems is recommended, and
      this can be partly achieved with predefined type tests. The beam data and test
      geometries of IAEA TECDOC 1540 have been used to test the analytical anisotropic
      algorithm (AAA) and pencil-beam convolution (PBC) algorithm of the Varian Eclipse
      treatment planning system. Beam models were created in Eclipse for 6 MV, 10 MV
      and 18 MV from the available beam data. Twelve test geometries were re-created in
      Eclipse, and the differences between Eclipse dose calculations and dose
      measurements were recorded. The AAA algorithm generally performed better than the
      PBC algorithm for the 12 tests, but both algorithms did not meet predefined
      tolerances for asymmetric wedge fields. An in-house monitor unit check program
      based on collimator and phantom scatter factors with tissue-phantom ratios was
      also tested and its calculations were found to agree with measurements to within
      3.2% for on-axis points.

PMID- 21731228
TI  - Dosimetric comparison of high dose rate brachytherapy and intensity-modulated
      radiation therapy for cervical carcinoma.
AB  - Intracavitary brachytherapy is an integral part of radiotherapy for locally
      advanced gynecologic malignancies. A dosimetric intercomparison of high dose rate
      intracavitary brachytherapy (HDR_BT) and intensity-modulated radiotherapy in
      cervical carcinoma has been made in the present study. CT scan images of 10
      patients treated with HDR_BT were used for this study. A sliding-window IMRT
      (IMRT_SW) and step-and-shoot IMRT plans were generated using 6-MV X-rays. The
      cumulative dose volume histograms of target, bladder, rectum and normal tissue
      were analyzed for both techniques and dose distributions were compared. It was
      seen that the pear-shaped dose distribution characteristic of intracavitary
      brachytherapy with sharp dose fall-off outside the target could be achieved with
      IMRT. The integral dose to planning target volume was significantly higher with
      HDR_BT in comparison with IMRT. Significant differences between the two
      techniques were seen for doses to 1 cc and 2 cc of rectum, while the differences
      in 1 cc and 2 cc doses to bladder were not significant. The integral doses to the
      nontarget critical and normal structures were smaller with HDR_BT and with IMRT.
      It is concluded that IMRT can be the choice of treatment in case of non
      availability of HDR brachytherapy facilities or when noninvasive treatments are
      preferred.

PMID- 21731229
TI  - The management of bladder exstrophy: Indian scenario.

PMID- 21731230
TI  - Exstrophy bladder: Effect of sigmoid colocystoplasty on physical growth and bone
      mineral density.
AB  - BACKGROUND AND AIMS: Introduction of intestinal tissue in the urinary tract
      results in numerous metabolic changes. This study investigates the effects of
      augmentation sigmoid colocystoplasty on the physical growth and bone
      mineralization in bladder exstrophy patients. MATERIALS AND METHODS: Physical
      growth, serum biochemistry and bone mineral density were assessed pre and post
      augmentation in 34 of 54 patients who were treated by staged sigmoid
      colocystoplasty for classical bladder exstrophy during the period 1985-2007.
      Physical growth was determined by comparing the height and weight for age with
      standard growth charts. Serum biochemistry included calcium, phosphate and
      alkaline phosphatase levels. Bone mineral density (BMD) was determined at the
      femoral head using the dual energy X-ray absorptiometry (DEXA) scan at 15 +/- 4.5
      months after the augmentation. The DEXA scan findings were compared with 22
      normal Indian children who served as controls and 18 unaugmented patients with
      bladder exstrophy. In 13 augmented patients, the DEXA scan could be repeated
      after an interval of six months. RESULTS: The mean percentile height and weight
      were comparable in the pre and post-augmentation period with no statistically
      significant difference (P=0.135 for height and P=0.232 for weight). Biochemical
      parameters of bone metabolism also did not show any statistically significant
      changes after colocystoplasty. The BMD was 0.665 +/- 0.062 g/cm(2) in the
      controls and 0.612 +/- 0.10 g/cm(2) in the unaugmented bladder exstrophy
      patients. In the augmented patients, the BMD was 0.645 +/- 0.175 g/cm(2) and six
      months later it was 0.657 +/- 0.158 g/cm(2). These differences were not
      statistically significant. CONCLUSIONS: In our study, no significant effects on
      the physical growth and bone mineral metabolism were observed in exstrophy
      bladder patients following sigmoid colocystoplasty.

PMID- 21731231
TI  - Esophageal atresia and tracheoesophageal fistula: Effect of pleural cover on
      anastomotic dehiscence.
AB  - BACKGROUND: A significant number of esophageal atresia and tracheoesophageal
      fistula patients have long gaps and a high propensity to leak. Anastomotic leak
      in esophageal atresia is associated with a significant morbidity and mortality.
      AIM: In a prospective randomized trial, we analyzed the risk factors leading to
      anastomotic dehiscence and studied the effect of pleural wrap as an additional
      vascular cover around the esophageal anastomosis. MATERIALS AND METHODS: Forty
      patients were divided into two groups A and B randomly. In 20 patients of group
      A, pleural wrap was utilized for covering the anastomosis and in 20 patients of
      group B, no such wrap was utilized. RESULTS: Both the groups were comparable
      regarding age, sex, weight, gap length, tension at anastomosis and the hospital
      stay. The overall leak rate was 25% (10/40) in both the groups. The leak rate was
      not significantly different in two groups whenever a gap length was less than 2
      cm or more than 3 cm. However, for a gap length of 2-3 cm, the leak rate in group
      A was 18% (2/11) and in group B was 50% (4/8) (P = 0.05). Thirty percent (3/10)
      of patients, whose anastomosis was under tension, leaked in group A as compared
      to 75% (6/8) in group B patients (P = 0.001). CONCLUSIONS: Use of pleural wrap
      was associated with less anastomotic dehiscence in patients with moderate gap
      esophageal atresia (2-3 cm) especially when the anastomosis was under tension.

PMID- 21731232
TI  - Choledochal cyst: A review of 79 cases and the role of hepaticodochoduodenostomy.
AB  - AIM: To analyze our experience of choledochal cysts. The results of complete
      excision of cyst and hepaticodochoduodenostomy have been analyzed in particular.
      MATERIAL AND METHODS:  PERIOD OF STUDY: January 1993 to August 2010. Apart from
      basic investigations, we did ultrasonography (USG) of abdomen, contrast-enhanced
      computerized axial tomography scan (CECT), endoscopic retrograde
      cholangiopancreatography (ERCP), operative cholangiogram, hepatic isotope scan
      (HIDA), magnetic resonance cholangiopancreatogram (MRCP) and choledochoscopy. The
      patients were divided into six groups according to the management done and the
      results analyzed. RESULTS: The total number of cases was 79 (Male : Female = 26 :
      53). The mean age of presentationwas 5.18 years. The most common mode of
      presentation was abdominal pain in 86% cases. Types of cysts - Type I: 63; Type
      IV: 12; Forme fruste: 1; Caroli's disease: 1; Cyst with atresia in the lower end
      of common bile duct: 2. Two patients of group A (cyst excision and Roux-en-Y
      hepaticojejunostomy) had recurrent pain and cholangitis. One patient required
      revision for stricture. In group E (n=53) (excision of cyst and
      hepaticodochoduodenostomy), three patients developed occasional epigastric pain
      and they responded to omeprazole. One patient developed anastomotic stricture and
      was lost to follow up. One patient of cyst with biliary atresia with biliary
      cirrhosis died. CONCLUSIONS: In choledochal cyst, complete excision of cyst and
      good bilioenteric anastomosis with wide stoma should be done.
      Hepaticodochoduodenostomy with wide stoma is a simple, quick procedure with
      preservation of normal anatomy and physiology and minimum complications. It also
      avoids multiple intestinal anastomoses and so should be the preferred approach.

PMID- 21731233
TI  - Glial heterotopia of maxilla: A clinical surprise.
AB  - Glial heterotopia is a rare congenital mass lesion which often presents as a
      clinical surprise. We report a case of extranasal glial heterotopia in a neonate
      with unusual features. The presentation, management strategy, etiopathogenesis
      and histopathology of the mass lesion has been reviewed.

PMID- 21731234
TI  - Congenital pouch colon and segmental dilatation of the colon: A report of two
      unusual cases.
AB  - This report describes two unusual cases of anorectal malformation. The first had
      a type III congenital pouch colon with a colovesical fistula. In the other very
      similar case, segmental dilatation of the colon was present along with
      penoscrotal hypospadias and, distally, a length of normal colon ending in a
      rectourethral fistula. In both patients, the appendix was short, stubby and a Y
      shaped duplication of the normal colon was present just proximal to the dilated
      segment of colon.

PMID- 21731235
TI  - Unusual association of polysplenia syndrome with abdominal teratoma.
AB  - Report of a hitherto unreported association of polysplenia, teratoma and
      eventration of diaphragm.

PMID- 21731236
TI  - Desmoplastic small round cell tumor of the pancreas: An unusual primary site for
      an uncommon tumor.
AB  - Pancreas is a rare location for desmoplastic small round cell tumor. The present
      case highlights the dilemma in diagnosis and ascertaining the site of tumor
      origin. Morphologic and immunohistochemical features were complemented with the
      molecular markers and tumor origin which was initially nebulous was subsequently
      confirmed on exploratory laparotomy.

PMID- 21731237
TI  - Renal tuberculosis in infancy.
AB  - We report a case of congenital renal tuberculosis in a 34-day-old child
      presenting as severe hematuria. Adequate antitubercular treatment may provide
      protection to fetus in subsequent pregnancies.

PMID- 21731238
TI  - Pancreatic cystic lesion in an infant.
AB  - Pancreatic cystic lesions are rare clinical entities. To the best of our
      knowledge, only 38 cases have been reported in the English literature in children
      under the age of 2 years. We present a 2-month-old infant with a cystic lesion in
      the head of pancreas. We reviewed the possible causes and present our dilemmas in
      the management of these patients.

PMID- 21731239
TI  - Non-traumatic anterior mediastinal abscess in childhood.
AB  - Anterior mediastinal abscesses (MAs) due to a non-traumatic etiology are
      extremely rare in childhood and only 13 such cases have been reported in the
      literature. We report a 5-year-old male child with disseminated staphylococcal
      infection and a large non-traumatic anterior MA, who had a successful recovery
      after surgical drainage of the abscess.

PMID- 21731240
TI  - Unresectable gastrointestinal stromal tumors.

PMID- 21731241
TI  - Re-pediatric laparoscopy: Facts and factitious claims.

PMID- 21731242
TI  - The last word.

PMID- 21731243
TI  - Diabetes and periodontitis.
AB  - The main aim of this review is to update the reader with practical knowledge
      concerning the relationship between diabetes mellitus and periodontal diseases.
      Exclusive data is available on the association between these two chronic diseases
      till date. Articles published on this relationship often provide the knowledge of
      definitions of diabetes mellitus and periodontal diseases, prevalence, extent,
      severity of periodontal disease, complications of diabetes along with the
      possible underlying mechanisms. The authors reviewed human epidemiological
      studies, cross-sectional observations and longitudinal cohort, case control that
      evaluated variables exclusively over the past 30 years and the predominant
      findings from the "certain" articles are summarized in this review. This review
      clarifies certain queries such as 1) Do periodontal diseases have an effect on
      the metabolic control of diabetes? 2) Does diabetes act as a risk factor of
      periodontitis? 3) What are the possible underlying mechanisms relating the
      connection between these two chronic diseases? 4) What is the effect of
      periodontal intervention on metabolic control of diabetes? After a thorough
      survey of literature, it was observed that diabetes acts as a risk factor in
      development of periodontitis as periodontitis is significantly aggravated in
      patients suffering from diabetes having long term hyperglycemia. Different
      mechanisms underlying the association between the accelerated periodontal disease
      and diabetes are emerging but still more work is required. Major efforts are
      required to elucidate the impact of periodontal diseases on diabetes. At the same
      time, patients are needed to be made aware of regular periodontal maintenance
      schedule and oral hygiene.

PMID- 21731244
TI  - Efficacy of a chairside diagnostic test kit for estimation of C-reactive protein
      levels in periodontal disease.
AB  - BACKGROUND: C-reactive protein [CRP] levels increase to hundreds of mg/mL within
      hours following infection. Studies have shown that serum CRP levels were elevated
      in periodontal disease. However, in all the previous studies, CRP levels were
      measured by using high-sensitivity CRP assay kits with minimal detection limits
      of 0.1 to 3 mg/L, which was much below the normal value of 10 mg/L. These high
      sensitivity CRP assays need a proper laboratory setup, and these methods cannot
      be used as a routine chair-side test in the dental office. AIM: The purpose of
      this study was to investigate the serum CRP levels in subjects with periodontal
      disease by using a rapid chair-side diagnostic test kit with a lower detection
      limit of 6 mg/L and to compare the CRP levels before and after periodontal
      therapy. MATERIALS AND METHODS: A total of 45 systemically healthy subjects were
      selected for the study. Subjects were divided into three groups: group A: healthy
      controls, group B: gingivitis, group C: periodontitis. Serum levels of CRP were
      determined by using a latex slide agglutination method with commercially
      available kit with lower detection limit of 6 mg/L. RESULTS: CRP was negative in
      all the 15 subjects in groups A and B at baseline, 7th and 30th day. CRP was
      positive only in 2 subjects in Group C at baseline and 7th day. CONCLUSION:
      Estimation of serum CRP by using a rapid chair-side diagnostic test kit is not of
      any significance in subjects with periodontitis.

PMID- 21731245
TI  - Evaluation of tumor necrosis factor-alpha (TNF-alpha) levels in plasma and their
      correlation with periodontal status in obese and non-obese subjects.
AB  - BACKGROUND: Obesity is emerging as a significant health problem worldwide and is
      a risk factor for various systemic diseases. Periodontal disease is a
      multifactorial inflammatory disease. Recent evidence points to a link between
      obesity and periodontal disease, and a role for tumor necrosis factor-alpha (TNF
      alpha) has been suggested. MATERIALS AND METHOD: FORTY NONDIABETIC SUBJECTS WERE
      DIVIDED INTO TWO GROUPS: group A (non-obese) included subjects with body mass
      index (BMI) of 18.5 to 27 kg/m2, and group B (obese) included subjects with
      BMI>27 kg/m2. The BMI, TNF-alpha levels in plasma and Periodontal Disease Index
      (PDI) scores were assessed, compared and correlated. RESULTS: Significantly
      higher PDI scores and TNF-alpha levels were found in the obese group as compared
      to those in the non-obese group. Also, a significant and positive correlation was
      seen between BMI and TNF-alpha, TNF-alpha and PDI as well as BMI and PDI.
      CONCLUSION: Increase in the levels of tumor necrosis factor-a in plasma and an
      increase in the severity of periodontal disease may be seen in subjects with a
      higher body mass index (BMI). This indicates that obesity may be detrimental to
      the periodontal health of individuals.

PMID- 21731246
TI  - Viability of bacteria in dental calculus - A microbiological study.
AB  - AIM: The aim of this study was (1) To investigate the viability of bacteria
      within supragingival and subgingival calculus, (2) To examine motility of
      bacteria, and (3) To identify bacterial morphotypes in calculus. MATERIALS AND
      METHODS: Supra and subgingival calculus were harvested from 30 subjects having
      clinical evidence of chronic inflammatory periodontal disease and were divided
      into two groups. Samples from both groups were immediately transported to the
      Department of Microbiology for gram staining, acridine orange staining, bacterial
      culture and to the Department of Oral Pathology for dark field microscopy.
      RESULTS: Gram staining revealed presence of bacteria within the samples.Dark
      field microscopic examination revealed presence of filamentous organisms,
      spirochetes, and motile short bacilli. Acridine orange fluorescent stain showed
      that the viable bacteria appeared apple green. Bacterial culture revealed
      presence of a variety of aerobic organisms. CONCLUSION: From the results, it
      appeared that viable bacteria were present within calculus especially within
      internal channels and lacunae.

PMID- 21731247
TI  - Quantitative estimation and correlation of serum albumin levels in clinically
      healthy subjects and chronic periodontitis patients.
AB  - AIM: The aim of this study was to evaluate the relationship between periodontal
      disease and general health status in adults using the serum albumin
      concentration. MATERIALS AND METHODS: A total of 100 patients of both genders
      with age range of 40 to 70 years were included in the study. Patients were
      divided into the following two groups: clinically healthy subjects and patients
      with periodontitis, that is, loss of attachment >=5 mm. Dental examinations were
      carried out at baseline and clinical attachment levels were measured at four
      sites. Serum albumin concentration was estimated by bromocresol green albumin
      method. RESULTS: The mean serum albumin levels for Group I was 4.47 g/dl with
      standard deviation (SD) of 0.276 and for Group II, the mean value of serum
      albumin was 4.61 g/dl with SD of 0.273. Using Student's unpaired 't' test, the
      difference between the serum albumin levels in Group I and Group II were found to
      be statistically significant (P=0.020). The mean body mass index values for Group
      I was 22.63 with a SD of 3.85, whereas the same for Group II was 22.23 with a SD
      of 4.21, which were on comparison, found to be nonsignificant (P=0.462).
      CONCLUSION: The findings of the clinical trial suggest an inverse relationship
      between the serum albumin concentration and chronic periodontal disease.

PMID- 21731248
TI  - A comparative study on the efficacy of a commercial fibrin adhesive (Tisseel) vis
      a-vis silk suture on wound closure following periodontal surgical procedures.
AB  - AIMS AND OBJECTIVES: To evaluate the efficacy of fibrin adhesive sealant
      (Tisseel((r))), a human biological tissue adhesive, as compared to conventional
      suture placement in pocket elimination and mucogingival surgical procedures.
      MATERIALS AND METHODS: The study sample consisted of 25 patients (10 male and 15
      female patients), in the age group of 25-40 years, with localized periodontitis
      in relation to the anterior region of the maxilla and mandible. They were divided
      into three surgical groups: Group I, Group II and Group III. Each of these groups
      was further divided into control and experimental groups. In all the control
      groups, the flaps/grafts were approximated with 4-0 black braided silk. In the
      experimental groups, the flaps/grafts were approximated with fibrin adhesive
      sealant (Tisseel(;)). Clinical parameters were taken pre-operatively.operatively
      and post-operatively on the 1(st), 2(nd), 3(rd), 7(th), and 10(th), day. RESULTS:
      The Fibrin Adhesive System (FAS) showed superior results in all the parameters
      measured, i.e., hemostasis, fixation of tissues, reduction in plaque and gingival
      index and probing depth postoperatively. CONCLUSION: The results of this study
      indicate that periodontal surgery using FAS enhances various periodontal
      regenerative surgical procedures.

PMID- 21731249
TI  - Comparison of oral hygiene and periodontal status in patients with clefts of
      palate and patients with unilateral cleft lip, palate and alveolus.
AB  - AIM: This study was conducted to analyze and compare the oral hygiene and
      periodontal status in patients with clefts of palate (CP) and patients with
      unilateral cleft lip, palate and alveolus (UCLPA). MATERIALS AND METHODS: The
      study group consisted of 120 cleft patients. Subjects were divided into two
      groups of 60 each. Group I - patients with UCLPA and Group II - patients with CP.
      For comparison, all the four quadrants were defined, Q1-right upper quadrant, Q2
      left upper quadrant, Q3-left lower quadrant and Q4-right lower quadrant, in both
      groups and the following parameters were recorded: Plaque Index (PI, Silness and
      Loe), Sulcus Bleeding Index (SBI, Muhlemann and Son), Probing Pocket Depth (PPD),
      Clinical Attachment Level (CAL), Mobility Index (Miller) and Radiographic Amount
      of Bone Loss. RESULTS: The periodontal destruction was seen to be higher in UCLPA
      patients compared with CP patients. The poor oral hygiene status, as indicated by
      higher values of PI, and the periodontal status, evaluated by SBI, PPD, CAL,
      mobility and Radiographic Amount of Bone Loss, were higher in patients with UCLPA
      than in patients with CP. CONCLUSION: In this study, patients with cleft lip,
      palate and alveolus had poor oral hygiene and periodontal status compared with
      patients with cleft palate.

PMID- 21731250
TI  - Clinical and histological evaluation of two dressing materials in the healing of
      palatal wounds.
AB  - BACKGROUND: Free gingival grafts have been used extensively for gingival
      augmentation procedures, but are associated with postoperative morbidity because
      of the open palatal wound. This study compares the clinical efficiency of two
      dressing materials, a non-eugenol-based dressing (Coe-PakTM) and a collagen
      dressing (Colla Cote((r))) on palatal wound healing. MATERIALS AND METHODS:
      Thirty-two patients in the age group of 25-50 years, who required gingival
      augmentation, were selected. Free gingival graft was harvested from the palatal
      mucosa and the wound was then protected using Coe-pak((r)) in control group and
      Colla Cote((r)) in test group. The subjective parameters pain and burning
      sensation were recorded on the 2(nd) and 7(th) day and the objective parameters
      colour and consistency were recorded on the 7(th) and 42(nd) day, using a visual
      analog scale. Thickness of the mucosa was measured using K file at baseline and
      42(nd) day. Histological examination was done on 42(nd) day. RESULTS: The
      subjective and objective parameters showed significant improvement in the test
      group when compared to control group. Histologically, there was a greater
      evidence of collagen formation and turn over in the test group than control
      group. CONCLUSIONS: Collagen-based dressing may thus offer significantly greater
      advantages over the traditional non-eugenol dressings.

PMID- 21731251
TI  - The efficacy of flapless implant surgery on soft-tissue profile comparing
      immediate loading implants to delayed loading implants: A comparative clinical
      study.
AB  - AIMS AND OBJECTIVES: To assess the efficacy of flapless implant surgery on soft
      tissue profile and to compare the clinical outcomes of flapless implant therapy
      on immediate loading (IL) implants to delayed loading (DL) implants. MATERIALS
      AND METHODS: The study sample consisted of 20 patients who were partially
      edentulous in the anterior maxillary region. They were divided into two groups.
      In group I (IL) 10 implants were placed and immediately provisionalized and
      restored with a metal ceramic crown on the 14th day. In group II (DL) 10 implants
      were placed and loaded after 4 months. Single-piece implants were used for the IL
      group and two-piece implants were used for the DL group. All soft tissue
      parameters i.e., modified plaque index (mPI), modified bleeding index (mBI),
      papillary index (PPI), marginal level of soft tissue (ML) and width of
      keratinized mucosa (WKM) were recorded at baseline, Day 60, Day 120 and Day 180.
      RESULTS: The success rate in group I was found to be 80%, which was lower than
      the success rate in group II which was found to be 90%. On comparison, there is
      no statistically significant difference in success rate between the two study
      groups. There was no statistically significant difference between the groups over
      time in parameters like mPI, mBI, ML and WKM. The mean PPI score in group II
      showed a significant increase from when compared to group I. CONCLUSION: The
      results of this study indicated that flapless implant surgery using either
      immediately loading implants or DL implants, demonstrate enhancement of implant
      esthetics.

PMID- 21731252
TI  - Modified Widman flap and non-surgical therapy using chlorhexidine chip in the
      treatment of moderate to deep periodontal pockets: A comparative study.
AB  - INTRODUCTION: It is a well established fact that periodontitis is caused by a
      group of highly specific microorganisms, organized as a bio-film on the tooth
      surface. Hence, therapeutic modalities are directed against elimination or
      adequate suppression of these organisms. Thorough debridement of these sites is
      possible mainly by scaling and root planing (SRP) and open- flap debridement in
      deeper sites. Open- flap debridement includes conventional surgical procedures
      such as the modified Widman flap procedure. Surgical procedures, however, have a
      number of disadvantages and hence efforts have been on at improving various non
      surgical approaches, which are directed more specifically at the microbial nature
      of periodontal disease. Use of local drug-delivery devices is one such approach.
      The combined therapy of SRP and local drug delivery has been showing promising
      results in improving all the parameters in periodontal disease. MATERIALS AND
      METHODS: This study compares the clinical, as well as, microbiological results of
      a split-mouth trial using modified Widman flap and non-surgical therapy of SRP
      and the use of a controlled release drug-delivery device (Chlorhexidine chip), in
      the management of moderate to deep pockets. RESULTS AND CONCLUSION: The results
      showed that the non-surgical most sites subjected to the non-surgical treatment
      were found to be maintainable without further deterioration, during the study
      period.

PMID- 21731253
TI  - Evaluation of clinical and metabolic changes after non surgical periodontal
      treatment of type 2 diabetes mellitus patients: A clinico biochemical study.
AB  - AIM: To evaluate the clinical and metabolic changes following nonsurgical
      periodontal therapy of type-2 diabetic patients and nondiabetic patients.
      MATERIALS AND METHODS: Fifteen nondiabetics and fifteen type-2 diabetics with
      moderate to severe periodontitis were selected after meeting inclusion and
      exclusion criteria. Periodontal pocket probing was performed using a Williams
      graduated periodontal probe and comparisons of the clinical and biochemical
      parameters like plaque index, gingival index, probing depth, glycated hemoglobin,
      and lipid profile (total cholesterol, high density lipoprotein, low density
      lipoprotein, triglycerides and very low density lipoprotein) were done between
      and within two groups at baseline and 3 month. RESULTS: A correlation was
      observed between clinical and biochemical parameters between and within two
      groups at baseline and 3 month. The P value of diabetic group was<0.001 in all
      clinical parameters (plaque index PI, Gingival index GI, and Probing Pocket Depth
      PPD) in diabetic and nondiabetic group, showed statistically highly significant
      difference in GI, PI, PPD, <.01 in Glycated Hemoglobulin (HbAlc1) in test group
      and<0.05 in control group showed statistically significant difference. The P
      value of test group was >0.05 in Lipid profile (total cholesterol, low density
      lipoprotein, high density lipoprotein, serum triglyceride, very low density
      lipoprotein) that showed no significant difference and in control group<0.05 in
      total Cholesterol, high density lipoprotein and <0.01 in Low density lipoprotein,
      Very Low Density Lipoprotein, and Serum Triglyceride, respectively, showed
      statistically significant in Total cholesterol, Low density lipoprotein, Very Low
      Density Lipoprotein, and Serum Triglyceride, not significant in high density
      lipoprotein. The P value >0.05 showed no statistical significance of correlation
      between the test and control groups. CONCLUSION: Both groups of patients showed
      an improvement in clinical and metabolic parameters assessed at 3 months after
      nonsurgical periodontal therapy.

PMID- 21731254
TI  - Idiopathic gingival enlargement and its management.
AB  - Idiopathic gingival enlargement is a proliferative fibrous lesion of the gingival
      tissue that causes esthetic and functional problems. Both genetically and
      pharmacologically induced forms of gingival enlargement exist. This case report
      addresses the diagnosis and treatment of a case of idiopathic gingival
      enlargement in a 13-year-old female. The patient presented with generalized
      diffuse gingival enlargement involving the maxillary and mandibular arches
      extending on buccal and lingual/palatal surfaces and covering incisal / occlusal
      third of the tooth resulting in difficulty in speech and mastication since last
      three years. Patient also gave a history of surgical treatment being carried out
      four years back in upper anterior region suggesting of recurrence. Biopsy report
      confirmed the diagnosis of gingival hyperplasia. Gingivectomy was carried out in
      all four quadrants by using four different methods.

PMID- 21731255
TI  - An innovative cosmetic technique called lip repositioning.
AB  - A clinical report describing the successful use of the lip repositioning
      technique for the reduction of excessive gingival display. A female patient aged
      34 years reported with a chief complaint of gummy smile and was treated with this
      technique performed under local anesthesia with the main objective to reduce
      gummy smile by limiting the retraction of elevator muscles (e.g., zygomaticus
      minor, levator anguli, orbicularis oris, and levator labii superioris). The
      technique is fulfilled by removing a strip of mucosa from maxillary buccal
      vestibule and creating a partial thickness flap between mucogingival junction and
      upperlip musculature, and suturing the lip mucosa with mucogingival junction,
      resulting in a narrow vestibule and restricted muscle pull, thereby reducing
      gingival display.

PMID- 21731256
TI  - Placement of endosseous implant in infected alveolar socket with large
      fenestration defect: A comparative case report.
AB  - Placement of endosseous implants into infected bone is often deferred or avoided
      due to fear of failure. However, with the development of guided bone regeneration
      [GBR], some implantologists have reported successful implant placement in
      infected sockets, even those with fenestration defects. We had the opportunity to
      compare the osseointegration of an immediate implant placed in an infected site
      associated with a large buccal fenestration created by the removal of a root
      stump with that of a delayed implant placed 5 years after extraction. Both
      implants were placed in the same patient, in the same dental quadrant by the same
      implantologist. GBR was used with the fenestration defect being filled with
      demineralized bone graft* and covered with collagen membrane**. Both implants
      were osseointegrated and functional when followed up after 12 months.

PMID- 21731257
TI  - Papillon-Lefevre syndrome: A report of two cases.
AB  - Papillon-Lefevre syndrome is a rare (1-4 cases per million) autosomal recessive
      disorder showing predominantly oral and dermatological manifestations in the form
      of aggressive periodontitis affecting both primary and permanent dentition and
      palmoplantar hyperkeratosis. Genetic studies have shown that mutations in the
      major gene locus of chromosome 11q14 with loss of function of cathepsin C gene
      are responsible for Papillon-Lefevre syndrome. This report presents two siblings
      with classic signs and symptoms of Papillon-Lefevre syndrome. The exact cause for
      periodontal destruction in patients with Papillon-Lefevre syndrome is not known
      but it is thought to be due to defect in neutrophil function, immune suppression
      and mutations in cathepsin C gene.

PMID- 21731258
TI  - Management of amlodipine-induced gingival enlargement: Series of three cases.
AB  - Gingival enlargement is one of the side effects associated with certain drugs.
      Amlodipine, a calcium channel blocker, used as antihypertensive drug has been
      found associated with gingival hyperplasia. This case series presents diagnosis
      and management of amlodipine-induced gingival hyperplasia. Amlodipine-induced
      gingival enlargement was diagnosed and managed by thorough scaling and root
      planning. Drug substitution and surgical intervention was performed in first two
      cases. The pathogenesis of gingival enlargement is uncertain and the treatment is
      still largely limited to the maintenance of an improved level of oral hygiene and
      surgical removal of the overgrown tissue. Several factors may influence the
      relationship between the drugs and gingival tissues as discussed by Seymour et
      al. Meticulous oral hygiene maintenance, switchover to alternative drug,
      professional scaling and root planning and surgical excision of enlarged gingival
      tissue may help overcome the effect of these drugs.

PMID- 21731259
TI  - Relevance of gingival crevice fluid components in assessment of periodontal
      disease - A critical analysis.
AB  - Monitoring infections which are episodic, site specific, localized or
      generalized, initiated by a number of microorganisms and assessed with
      measurement devices that have inherent shortcomings presents a difficult task.
      The lack of precise clinical criteria for assessment of periodontal disease has
      led to a search for alternative means of determining active disease sites,
      predicting future sites of breakdown and evaluating response to therapy. This
      paper highlights the potential array of biomarkers present in gingival crevice
      fluid (GCF) and provides an insight of which of these factors has the greatest
      diagnostic potential. The rationale behind using GCF as sampling source is also
      described. Finally it discusses the possible use of predictive chair side
      diagnostic tests in periodontitis.

PMID- 21731260
TI  - Orthodontic intervention to resolve periodontal defects: An interdisciplinary
      approach.
AB  - In the new era of esthetics, Orthodontic therapy has gained tremendous acceptance
      by adults. However,treating adults is more challenging as they present with
      multiple periodontal problems compromising orthodontic treatment. Hence, to
      provide optimal treatment to adult patients an active interaction between
      orthodontist and periodontist is imperative.This article addresses the dilemmas
      encountered during the treatment of orthodontic patients with periodontal
      defects.

PMID- 21731261
TI  - Review of paraneoplastic syndromes associated with oropharyngeal squamous cell
      carcinoma.
AB  - Malignancies are usually preceded by the presence of various paraneoplastic
      syndromes (PNS), which could be the indirect and/or remote effects of the
      metabolites produced by neoplastic cells. PNS manifested by oropharyngeal
      squamous cell carcinomas, which is the most common head and neck malignancy, are
      highlighted in this review. Knowledge of the clinical spectrum of these syndromes
      will equip the oral physician for early diagnosis and management of these hidden
      malignancies, especially of the pharyngeal region.

PMID- 21731262
TI  - Ageing and its implications.
AB  - Ageing processes are defined as those that increase the susceptibility of
      individuals, as they grow older, to the factors that eventually lead to death. It
      is a complex multi-factorial process, where several factors may interact
      simultaneously and may operate at many levels of functional organization. The
      heterogeneity of ageing phenotype among individuals of the same species and
      differences in longevity among species are due to the contribution of both
      genetic and environmental factors in shaping the life span. The various theories
      of ageing and their proposed roles are discussed in this review.

PMID- 21731263
TI  - Early detection of oral cancer: PAP and AgNOR staining in brush biopsies.
AB  - AIM: The aim of this study was to determine the diagnostic accuracy of routine
      Papanicolaou stain (PAP) and Silver stained Nucleolar Organizer Regions (AgNOR)
      staining in brush biopsies taken from suspected oral lesions for early detection
      of oral cancer. MATERIALS AND METHODS: Brush biopsies were collected from
      macroscopically suspicious lesions of the oral cavity of 34 patients and 10
      normal-aged and sex-matched controls. The numbers of AgNORs were counted in 100
      squamous epithelial cell nuclei per slide after silver staining of the smears
      (Ploton's one-step method). RESULTS: Sensitivity and specificity of PAP analysis
      in the oral smears for detection of oral cancer and normal cells was 91.176% and
      100%. The positive and negative prediction values were 100% and 76.92%,
      respectively. Sensitivity and specificity of AgNOR analysis in the oral smears
      for detection of oral cancer and normal cells was 100%. The positive and negative
      prediction values were 100% each. CONCLUSION: Based on the above facts, we
      conclude that brush biopsy in conjunction with AgNOR staining is an easily
      practicable, non-invasive, safe and accurate screening method for the detection
      of macroscopically suspicious oral cancerous lesions. Because of its simple
      technique and high reliability for cellular proliferation, AgNOR staining in
      brush smears can be used as an adjunct to other routine cytological diagnoses for
      the early detection of oral cancer. However, further investigations with more
      number of study samples will be needed to establish this correlation beyond
      doubt.

PMID- 21731264
TI  - Adenomatoid odontogenic tumor associated with dentigerous cyst in posterior
      maxilla: A case report and review of literature.
AB  - Adenomatoid odontogenic tumor (AOT)-a benign (hamartomatous) lesion of
      odontogenic origin-is an uncommon tumor which affects young individuals with a
      female predominance, mainly in the second decade. This lesion is most commonly
      located in the anterior maxilla and is usually associated with an impacted canine
      tooth. This is a case report of a 39-year-old female patient presented with a
      large AOT of the posterior maxilla associated with an impacted second molar - a
      very rare situation.

PMID- 21731265
TI  - Florid cemento osseous dysplasia in association with dentigerous cyst.
AB  - We present a case of florid cemento-osseous dysplasia occurring in a 20-year-old
      Indian woman. The subject presented with three lesions involving the maxillary
      right quadrant, maxillary left quadrant and mandibular left quadrant. The
      mandibular left quadrant also demonstrated a cyst.The diagnosis was made by
      correlating the clinical presentation with that of the radiological and
      histopathological findings. This is a rare entity because of an unusual
      combination of Asian race along with the association of dentigerous cyst.

PMID- 21731266
TI  - Primary intraosseous carcinoma of the mandible: A report of two cases.
AB  - Primary intraosseous carcinoma arising as a de novo lesion is a unique and rare
      carcinoma affecting the jaws, especially at younger ages. Two case reports, a 26
      year-old Indian female with primary intraosseous squamous cell carcinoma and a 16
      year-old Indian male with intraosseous carcinoma arising in an odontogenic cyst,
      both within the body of the mandible, are presented here.

PMID- 21731267
TI  - Primary non-Hodgkin's lymphoma of the mandible.
AB  - Primary non-Hodgkins's lymphoma is a very uncommon lesion, accounting for 0.6% in
      jaws. As the lesions frequently resemble other disease such as chronic
      osteomyelitis, odontogenic or any secondary neoplasms, further evaluation and
      histopathologic examination allow early identification for appropriate treatment.
      The purpose of this case report is to describe a rare case of non-Hodgkin's
      lymphoma of the mandible, explore the diagnosis and workup based on
      immunohistochemistry.

PMID- 21731268
TI  - Keratoameloblastoma of the mandible.
AB  - Keratoameloblastoma is a very rare ameloblastoma variant defined by extensive
      squamous metaplasia and keratinization. There are 13 previously reported cases in
      the literature, with a male predilection of 3:1. A 38-year-old male presented
      with a painless mandibular swelling which had been progressively increasing in
      size for 18 months. The incisional biopsy was misdiagnosed as basaloid squamous
      carcinoma. Owing to financial constraints, the patient had mandibular resection a
      decade after first noticing the growth, during which the clinical course was
      essentially benign, thus casting doubt on the initial diagnosis. The final
      histological diagnosis for both the incisional and resection biopsy specimens was
      keratoameloblastoma.

PMID- 21731269
TI  - A rare presentation of dens in dente in the mandibular third molar with extra
      oral sinus.
AB  - The unusual case of dense in dente in mandibular molar area with extra oral sinus
      in a 30-year-old female is presented. The chief complaint of the patient was
      wound formation and pus discharge from the right side of lower jaw for many
      years. Clinical examination revealed extra oral sinus and mild swelling in
      vestibular region opposite the right mandibular molars. On radiographical
      examination, right mandibular third molar had bulbous root associated with
      periapical radiolucency. It appeared that there was a tooth within a tooth and
      the invagination extended nearly to the root apex. A clinical diagnosis of dense
      in dente Type III was confirmed by stereomicroscopy of ground section of the
      tooth. Extra oral sinus healed after extraction of the mandibular third molar
      within a month.

PMID- 21731270
TI  - A cumulative analysis of odontogenic cysts from major dental institutions of
      Bangalore city: A study of 252 cases.
AB  - BACKGROUND: The objective of this study was to perform a cumulative analysis of
      odontogenic cysts obtained from the data of major dental institutions of
      Bangalore city, as well as to evaluate their distribution during a 5-year period
      and compare the results with other international studies. MATERIALS AND METHODS:
      Data for the study were obtained from the reports of patients diagnosed with
      odontogenic cysts between 2005 and 2010 from different dental institutions of
      Bangalore. Case records of patients that fit the histological classification of
      the World Health Organization (WHO) (2005) were included in the study and the
      following variables were analyzed: age, gender, anatomic location, and
      histological type. RESULTS: In a total of 252 cyst specimens diagnosed, 79.76%
      were odontogenic cysts and 20.24% were nonodontogenic cysts. Among the
      odontogenic cysts most frequent lesions were radicular cysts (50.25%), followed
      by keratocysts (27.36%) and dentigerous cysts (22.39%). CONCLUSIONS: Our study
      provides a cumulative data of odontogenic cysts in the population of Bangalore
      city. The results of our study showed a similar frequency of odontogenic cysts as
      compared to other populations of the world, with radicular cyst being identified
      as the most frequent odontogenic cyst. Keratocyst was the second most common cyst
      followed by dentigerous cyst.

PMID- 21731271
TI  - Microwave processing: A boon for oral pathologists.
AB  - BACKGROUND: Research in oral and maxillofacial pathology has unlimited potential.
      We use every technology available to us for better and faster reliable diagnosis.
      But in most institutions, private laboratories and multispecialty hospitals,
      tissue processing takes considerable time, and therefore delays the diagnosis,
      which is required in urgent cases. We, in this institution, conducted a study to
      hasten the processing by using a simple kitchen microwave. AIM: To analyze tissue
      sections processed by microwave as compared to the gold standard of conventional
      processing. SETTINGS AND DESIGN: Studies published from 1970 till 2008, used body
      tissues such as brain, liver, kidney, heart, and lungs, for microwave processing.
      Oral tissues were not processed in microwave till now, except one study by Dr
      Shivaparthasundaram et al., in 2008. This is the second such study that used a
      sample size of 50 cases. MATERIALS AND METHODS: A kitchen microwave was used for
      irradiation of the tissues. Conventional processing was carried out as per
      departmental protocol. A total of 50 microwave-coded slides were mixed with 50
      conventional slides. All 100 slides were evaluated by four different
      pathologists. STATISTICAL ANALYSIS: The result was subjected to statistical
      analysis using Chi-square test. RESULT AND CONCLUSION: It was found that to make
      a diagnosis, microwave-processed tissue were at par with the conventional
      technique. Thus, it is time to move on from conventional processing to microwave
      processing to yield faster and reliable results.

PMID- 21731272
TI  - Tooth decay in alcohol and tobacco abusers.
AB  - BACKGROUND: Alcohol and tobacco abuse are detrimental to general and oral health.
      Though the effects of these harmful habits on oral mucosa had been demonstrated,
      their independent and combined effect on the dental caries experience is unknown
      and worthy of investigation. MATERIALS AND METHODS: We compared 268 alcohol-only
      abusers with 2426 alcohol and tobacco abusers in chewing and smoking forms to
      test the hypothesis that various components of their dental caries experience are
      significantly different due to plausible sociobiological explanations. Clinical
      examination, Decay, Missing, Filled Teeth (DMFT) Index and Oral Hygiene Index -
      Simplified were measured in a predetermined format. Descriptive statistics, Chi
      square test and one-way ANOVA analysis were done using SPSS Version 16.0. RESULT:
      The mean DMFT were 3.31, 3.24, 4.09, 2.89 for alcohol-only abusers, alcohol and
      chewing tobacco abusers, smoking tobacco and alcohol abusers, and those who
      abused tobacco in smoke and smokeless forms respectively. There was no
      significant difference between the oral hygiene care measures between the study
      groups. Presence of attrition among chewers and those with extrinsic stains
      experienced less caries than others. DISCUSSION AND CONCLUSION: The entire study
      population exhibited a higher incidence of caries experience. Use of tobacco in
      any form appears to substantially increase the risk for dental caries. Attrition
      with use of chewing tobacco and presence of extrinsic stains with tobacco use
      appear to provide a protective effect from caries. The changes in oral micro
      flora owing to tobacco use and alcohol may play a critical role in the initiation
      and progression of dental caries.

PMID- 21731273
TI  - A rapid and noninvasive method to detect dried saliva stains from human skin
      using fluorescent spectroscopy.
AB  - OBJECTIVE: Saliva is one of the vital fluids secreted in human beings.
      Significant amount of saliva is deposited on the skin during biting, sucking or
      licking, and can act as an important source in forensic evidence. An enzyme,
      alpha amylase, gives a characteristic emission spectrum at 345-355 nm when
      excited at 282 nm and this can be identified by using fluorescent spectroscopy
      and can help in forensic identification. This study describes a rapid method to
      detect dried saliva on the human skin by fluorescent spectroscopy. MATERIALS AND
      METHODS: This study included 10 volunteers, who deposited their own saliva on
      skin of their ventral forearm by licking and water on the contralateral arm as
      control. This study was carried out at Central Leather Research Institute,
      Chennai. STUDY DESIGN: Ten volunteers deposited their own saliva on skin of their
      ventral forearm by licking. A control sample of water was deposited at the
      contralateral arm. Each sample was excited at 282 nm and emission spectrum was
      recorded. RESULTS: The emission spectra of 10 swab samples taken from dried
      saliva were characterized at the primary peak of 345 to 355 nm whereas the
      emission spectrum of water as a control was recorded at 362 nm. CONCLUSION: The
      presence of emission spectrum at 345-355 nm with excitation at 282 nm proves to
      be a strong indicator of saliva deposited on human skin.

PMID- 21731274
TI  - Morphometry of the basal cell layer of oral leukoplakia and oral squamous cell
      carcinoma using computer-aided image analysis.
AB  - OBJECTIVES: To study and compare the changes in nuclear and cellular size, shape
      and nuclear-cytoplasmic ratio of the cells in the basal layer of oral leukoplakia
      and well-differentiated oral squamous cell carcinoma (SCC) with normal buccal
      mucosa, using computer-aided image analysis in tissue sections. STUDY DESIGN:
      This was a retrospective study conducted on tissue sections on a total number of
      70 cases to determine the various morphometric parameters. The data collected in
      this study were analyzed statistically by computing descriptive statistics, viz.,
      percentage, mean, standard deviation, standard error of mean, 95% confidence
      interval for mean. The difference in the control and study groups for various
      diagnostic variables was compared by means of analysis of variance (ANOVA),
      Student's t-test for independent samples, wherever applicable. Mann-Whitney U
      test and Kruskal-Wallis test were used where the data were found to be
      asymmetrical and the standard deviations were also different. The results were
      considered statistically significant whenever P <= 0.05. RESULTS: Our results
      were significant for the morphometric parameter, size. The values of nuclear
      perimeter and area, cellular perimeter and area increased gradually from the
      normal buccal mucosa to leukoplakia, reaching the highest value in SCC. There was
      statistically significant difference in the nuclear and cellular areas to
      differentiate between leukoplakia and squamous cell carcinoma. Two variables
      which were used to study the shape, "form perimeter (PE)" and "contour index
      (CI)", showed significant difference between normal buccal mucosa and leukoplakia
      and between normal buccal mucosa and SCC. The morphometric parameter, nuclear
      cytoplasmic ratio, in our results showed an increase in leukoplakia and SCC
      compared to normal buccal mucosa, but the difference was not significant between
      leukoplakia and SCC. CONCLUSION: The morphometric parameter, size, was useful to
      differentiate between normal, potentially malignant leukoplakia and SCC.

PMID- 21731275
TI  - Immunohistochemical expression of EGP40, a tumor marker, in different grades of
      oral squamous cell carcinoma.
AB  - AIM: The aim of this study was to see the distribution and pattern of staining of
      epithelial glycoprotein 40 EGP-40 (also known as GA733-2, ESA, KSA, 17-1A
      antigen) in the different grades of OSCC. MATERIALS AND METHODS: 30 biopsy
      reports retrieved from the files of the Department of Oral Pathology and
      Microbiology, College of Dental Surgery, Manipal were used. These comprised of 10
      microslides each of 3 different histological grades of Oral Squamous Cell
      Carcinoma, namely Well Differentiated, Moderately Differentiated and Poorly
      Differentiated carcinomas. Immunoperoxidase staining for IgG, was performed by
      the unlabelled antibody peroxidase-antiperoxidase complex (PAP) method. The
      criteria used to define an antigen positive area were: Homogenous /Patchy
      staining of the section and Cytoplasmic/ Membranous staining of the tumor cells.
      RESULTS: The expression of EGP 40 in different grades of OSCC showed an inverse
      relationship to differentiation and a direct relationship with the proliferation
      of the tumor cells and its expression became more pronounced as the grade
      worsened i.e. from well to poorly differentiated OSCC. CONCLUSION: In the present
      study, the surface antigen EGP40 (Ep-CAM) was detected in the different grades of
      OSCC with its expression becoming more pronounced as the grade worsened i.e. from
      well to poorly differentiated OSCC. However, further studies are required to
      understand the dualistic role of EGP40 (Ep-CAM) in mediating cell to cell
      adhesion preventing cell scattering and its heterogeneous expression in promoting
      tumor invasion and metastasis and also to determine its exact role and
      significance at a practically applicable level.

PMID- 21731276
TI  - Oral lesions associated with nevirapine-related Stevens Johnson syndrome: A
      report of four cases.
AB  - Nevirapine is a non-nucleoside reverse transcriptase inhibitor, widely used in
      combination with other antiretroviral agents for treatment of HIV infection.
      Steven Johnson syndrome (SJS) is the major toxicity of nevirapine. We describe
      here four cases of SJS in HIV seropositive patients following nevirapine therapy.
      In all four cases cutaneous hypersensitivity reaction was seen with extreme oral
      lesions, three patients presented clinically with elevated liver enzymes and
      hepatitis, and two patients had ocular involvement.

PMID- 21731277
TI  - Intraoral presentation of multiple malignant peripheral nerve sheath tumors
      associated with neurofibromatosis-1.
AB  - Neurofibromatosis-1 (NF-1) is a relatively common autosomal dominant disease
      characterized by multiple cutaneous fibromatoses and cafe au lait spots. It is
      associated with the mutation of NF-1 gene, a tumor suppressor gene located on
      chromosome 17q11.2. Hence, it can be considered as a familial cancer
      predisposition syndrome in which the affected individuals are at increased risk
      of developing malignancies. Intraoral neurofibromas associated with NF-1 are
      quite common, but the occurrence of malignant peripheral nerve sheath tumor
      (MPNST) in the oral cavity is very rare. Oral MPNST can occur either de novo or
      by malignant transformation of neurofibromas or very rarely can represent a
      metastatic lesion. Here, we present a case of MPNST involving the maxillary
      region, in a patient with NF-1. Since MPNST often creates a diagnostic dilemma,
      histopathologic criteria for the diagnosis of MPNST are also discussed.

PMID- 21731278
TI  - Benign fibroxanthoma of the mandible.
AB  - Histiocytomas constitute a large group of tumors, the classification of which
      created a lot of confusion in the past. For this reason, various attempts were
      carried out during the last years so that a widely accepted classification system
      could be defined. Fibroxanthomas, according to contemporary data, are classified
      into benign histiocytomas and they are mostly located at the skin of extremities.
      They are rarely localized in the area of the head and neck, where they are found
      commonly in soft tissue. Fibroxanthomas located at the bones of oral and
      maxillofacial region are extremely rare. The purpose of this paper is to present
      a case of a fibroxanthoma located at the mandible as well as to analyze the
      histological findings of the lesion on which the diagnosis and differential
      diagnosis were based.

PMID- 21731279
TI  - Bilateral maxillary brown tumors in a patient with primary hyperparathyroidism:
      Report of a rare entity and review of literature.
AB  - Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and
      peritrabecular fibrosis due to hyperparathyroidism, resulting in a local
      destructive phenomenon. The classical "brown tumor" is commonly seen in ends of
      long bones, the pelvis and ribs. Facial involvement is rare and, when present,
      usually involves the mandible. We report a case of 60-year-old male with a rare
      initial presentation of primary hyperparathyroidism with bilateral maxillary
      brown tumors. The present case represents the third report of the bilateral
      maxillary brown tumors in a patient with primary hyperparathyroidism.
      Differential diagnosis is important for the right treatment choice. It should
      exclude other giant cell lesions that affect the maxillae.

PMID- 21731280
TI  - Odontoameloblastoma.
AB  - Odontoameloblastoma (OA) is an extremely rare mixed odontogenic tumor with both
      epithelial and mesenchymal components. OA develops from proliferating odontogenic
      epithelium and mesenchymal tissue. Till date, around 20 cases have fulfilled the
      histologic criteria of the current World Health Organization (WHO) histologic
      classification of odontogenic tumors. It affects predominantly young patients
      with a median age of 20.12 years, and has a predilection for males and occurs in
      posterior segments of either jaw with slight inclination for mandible. Review of
      literature shows only three reported cases in the anterior mandible. Here, we
      report a case of OA in the anterior mandible.

PMID- 21731281
TI  - Peripheral ossifying fibroma.
AB  - Here, we present a case report of peripheral ossifying fibroma (POF) in an adult
      lady in her fourth decade of life. This case report comprises the growth that
      occurred in the mandibular anterior region with displacement of anterior teeth,
      its satisfactory management and literature review. POF represents a reactive
      benign lesion of connective tissue and is not the soft tissue counterpart of
      ossifying fibroma and is also not related anyhow to peripheral odontogenic
      fibroma. POF in the age of 45 years, arising in the mandibular anterior region,
      is an occasional entity. Careful clinical examination and histopathology findings
      should be correlated to conclude the final diagnosis.

PMID- 21731282
TI  - Erythrodontia in congenital erythropoietic porphyria.
AB  - Congenital erythropoietic porphyria (CEP) is one of the rarest of porphyrias
      occurring worldwide. CEP is a very rare genetic autosomal recessive disease, with
      mutation in the gene that codifies uroporphyrinogen-III synthase, leading to
      porphyrin accumulation in many tissues, with marked skin photosensitivity,
      hemolytic anemia with splenomegaly and a decreased life expectancy. We report a
      case of Gu;nther's disease in view of its rarity along with a description of this
      interesting condition. An 18-month-old female baby with clinical, hematological
      and biochemical profile of CEP was reported with marked skin photosensitivity
      over face and hands. She had erythrodontia with delayed eruption of teeth. When
      evaluating erythrodontia of uncertain cause, we advocate maintaining a high
      degree of awareness for porphyria, especially for CEP as it is the rarest among
      porphyria and is a life-threatening condition.

PMID- 21731283
TI  - Ectomesenchymal chondromyxoid tumor: Review of literature and a report of a rare
      case.
AB  - Ectomesenchymal chondromyxoid tumor (ECMT) is a rare benign intraoral tumor.
      Clinically, it presents as a slow growing, painless, firm, submucosal sweling
      exclusively occurring on the anterior dorsum of the tongue. Till date only 40
      cases have been reported in literature. Histopathologically the tumor is
      characterized by a well circumscribed, lobular proliferation of round, polygonal,
      ovoid or fusiform cells in a net-like pattern in a myxoid to chondromyxoid
      background. Here, we present a rare case of ECMT occurring in a 7-year-old boy
      and throw some light on this distinct entity.

PMID- 21731284
TI  - Schwannoma causing resorption of zygomatic arch.
AB  - Schwannoma (also known as neurilemmoma, peripheral glioma and peripheral nerve
      sheath tumor) is a common, histologically distinctive, benign, usually
      encapsulated, peripheral nerve tumor of Schwann cell origin. Schwannomas can
      appear anywhere in the body, but are more frequently reported in the head and
      neck with an incidence of 25-48% in maxillofacial region. Resorption of bones due
      to schwannoma is rarely noticed in maxillofacial region. We hereby present a case
      report of schwannoma in a 35-year-old female, causing resorption of zygomatic
      arch along with review of literature.

PMID- 21731285
TI  - Aggressive fibromatosis of anterior maxilla.
AB  - Aggressive fibromatosis is a comparitively rare tumor with unpredictable growth
      and varying local recurrence rates. It does not develop distant metastases but
      locally it shows an aggressive and infiltrative behavior. Clinically, aggressive
      fibromatosis manifests as a painless, firm, often rapidly enlarging mass, fixed
      to underlying bone or soft tissue. It is never encapsulated. Histologically, it
      is rich in collagen and fibroblastic cells that are devoid of hyperchromatic or
      atypical nuclei, but with more variable cellularity in different tumor sections.

PMID- 21731286
TI  - The epithelioid blue nevus: A rare intraoral nevomelanocytic tumor.
AB  - The epithelioid blue nevus (EBN) is considered a cutaneous marker of the Carney
      complex. Sporadic EBN has been reported in patients not exhibiting the Carney
      complex. The EBN does not exhibit unique clinical features that help to
      differentiate it from other lesions and is often provisionally diagnosed as an
      acquired melanocytic nevus, or a malignant melanoma. A 52-year-old African
      American female had a 3-4 mm bluish macule of the left anterior hard palate. An
      excisional biopsy was performed to rule out an incipient melanoma. Formalin
      fixed, hematoxylin and eosin-stained sections were examined microscopically. On
      the basis of histopathological features, a diagnosis of EBN was rendered. We
      document a case of the rare EBN affecting the oral mucosa. The patient did not
      exhibit any features associated with the Carney complex. Two years post
      operatively, there is no evidence of a recurrent tumor.

PMID- 21731287
TI  - Bilateral dentigerous cyst in a non-syndromic patient: Report of an unusual case
      with review of the literature.
AB  - Dentigerous cysts are the most common developmental cysts of the jaws, most
      frequently associated with impacted mandibular third molar teeth and impacted
      canines. Bilateral dentigerous cysts are rare and occur typically in association
      with a developmental syndrome. The occurrence of bilateral dentigerous cysts is
      rare and, to date, only 21 cases have been reported in literature till 2009.
      Here, we report a case of bilateral dentigerous cysts in maxillae of non
      syndromic 10-year-old patient with brief review of literature.

PMID- 21731288
TI  - Extranodal NK/T-cell lymphoma, nasal type (angiocentric T-cell lymphoma): A
      review about the terminology.
AB  - Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a rare lymphoid neoplasm,
      which in the past has been grouped with a variety of granulomatous diseases. It
      is an aggressive non-Hodgkin's type characterized clinically by aggressive,
      nonrelenting destruction of the midline structures of the palate and nasal fossa.
      Despite the malignant clinical course, histological diagnosis can be difficult
      because of extensive tissue necrosis and multiple biopsies that are often
      required and has an ominous prognosis, as the average survival rate is between 6
      and 25 months as reported with a large number of Asian studies. Several American
      and European studies have shown similar results. This is the case report of a 60
      year-old male patient who presented with nasal obstruction and foul smelling,
      ulcerative lesion over the palate of 6 months duration, which had been treated
      with antibiotics and anti-inflammatories without success. After performing a
      number of diagnostic tests, it was found histologically and confirmed by
      immunohistochemical analysis that the patient had an ENKL, nasal type (also known
      as angiocentric T-cell lymphoma).

PMID- 21731289
TI  - Leiomyoma of the mandible in a child.
AB  - Leiomyomas are the benign tumors of the smooth muscle that usually arise in the
      gastrointestinal system and in the uterus. Oral leiomyomas are uncommon due to
      the paucity of the smooth muscles in the mouth (except in blood vessels) and
      those of the mandible are extremely rare. Leiomyomas have been classified as
      solid, angiomyoma (vascular leiomyoma), and epithelioid variants. Here, we report
      a rare case of leiomyoma of the mandible in a 9-year-old child, together with
      conventional histopathologic and immunohistochemical findings.

PMID- 21731290
TI  - Aneurysmal bone cyst of the mandible: A case report and review of literature.
AB  - Aneurysmal bone cyst (ABC) is rare benign lesions of bone which are infrequent in
      craniofacial skeleton. ABC's are characterized by rapid growth pattern with
      resultant bony expansion and facial asymmetry. We describe a case of ABC in a 25
      year old male patient affecting the body of the mandible with expansion and
      thinning of the buccal and lingual cortical plates. Treatment consisted of
      surgical curettage of the lesion. A one year follow- up showed restoration of
      facial symmetry and complete healing of the involved site.

PMID- 21731291
TI  - Clear cell unicystic ameloblastoma.
AB  - Clear cell differentiation in unicystic ameloblastoma with inclusion of many
      other histologic variants in the same tumor is a very rare occurrence. Here, we
      report a case of a well-circumscribed large mandibular swelling in a 22 - year
      old female. The lesion was histopathologically diagnosed as unicystic
      ameloblastoma which showed multiple histologic patterns and clear cell
      differentiation. The tumor was treated with surgical enucleation and chemical
      cauterization. A follow up of 20 months has shown no recurrence after initial
      surgery.

PMID- 21731292
TI  - Traumatic pseudolipoma causing facial asymmetry: An uncommon pathology and review
      of its pathogenesis.
AB  - We present an uncommon case of traumatic pseudolipoma in a 24-year-old female,
      causing facial asymmetry. Literature review suggests trauma as a possible
      etiology for its pathogenesis, which was present in this case. Microscopically,
      sometimes it is difficult to differentiate between normal adipose tissue and
      lipoma. Clinician must provide accurate clinical information in order to make a
      definitive diagnosis of traumatic pseudolipoma. Its pathogenesis has also been
      highlighted in this article.

PMID- 21731293
TI  - Telengiectactic osteosarcoma.

PMID- 21731294
TI  - A case of swelling in the right maxilla.

PMID- 21731295
TI  - State of the globe: the unglamorous side of infectious diseases: parasites.

PMID- 21731296
TI  - Genotypic Characterization of Staphylococcus aureus Obtained from Humans and
      Bovine Mastitis Samples in India.
AB  - AIM AND BACKGROUND: Staphylococcus aureus is a major human pathogen that also
      causes important infections in cattle and sheep. The present study aimed to test
      genetic diversity among strains of S. aureus isolated from cattle (n=34) and
      humans (n=22) by DNA typing. MATERIALS AND METHODS: Fluorescent amplified
      fragment length polymorphism (FAFLP) is the genotyping tool used in the study.
      The presence of the mecA and Panton-Valentine leukocidin (PVL) genes among these
      strain groups was also checked. RESULTS: A dendrogram deduced from FAFLP showed
      that all the strains clustered into 10 groups (A-J) with a relative genetic
      divergence of less than 8%. Sixty-seven percent of the isolates from bovine
      sources clustered together in two clades (A and H), while another major cluster
      with 13 isolates (59%) (Cluster G) had all strains from a human host. The
      remaining strains from both the hosts clustered independently into smaller
      clusters with the exception of two strains of human origin, which clustered along
      with a bovine cluster. Thirteen strains belonging to cluster G were highly
      clonal. About 77% of strains obtained from human infections were methicillin
      resistant S. aureus (MRSA), whereas only 29% of strains from bovine origin were
      MRSA. Only three strains from human origin showed PVL positive, while no strain
      from cattle had PVL genes. The complete absence of PVL genes in all the bovine
      strains in the study appears to be significant. CONCLUSIONS: FAFLP can be
      successfully applied to assess the genetic relationship of S. aureus isolates
      from different hosts. The study also provided the valuable epidemiological data
      on S. aureus from bovine sources in India, which is lacking.

PMID- 21731297
TI  - Awareness regarding the systemic effects of periodontal disease among medical
      interns in India.
AB  - BACKGROUND: Medical curriculum does not provide required space for oral health;
      hence, many medical interns are unfamiliar with the oral cavity and oral health
      research. AIMS: To study the level of awareness regarding systemic effects of
      periodontal disease among medical interns. SETTINGS AND DESIGN: A cross-sectional
      qualitative study recruiting medical interns from two medical institutions
      affiliated to two different universities in Southern India. MATERIALS AND
      METHODS: Study was carried out in two medical institutions affiliated to two
      different universities in Southern India. A total of 143 interns participated in
      the study. Each participant was given a self-administered, pre-tested, multiple
      choice question-type questionnaire to solve on the spot. In order to summarise
      the awareness level, respondents were graded on a five-level scale as poor, fair,
      good, very good, and excellent. STATISTICAL ANALYSIS USED: Percentages,
      proportions. RESULTS: A total of 67 respondents (47%) had fair; 60(42%), poor;
      and 18(11%), good level of awareness regarding the systemic effects of
      periodontal disease. Only 23(16%), 17(12%), 12(8%), 6(4%) and 4(3%) respondents
      were aware that the periodontal disease may be the possible risk factor for
      coronary heart disease, cerebral infarction, diabetes mellitus, hospital-acquired
      pneumonia, and preterm labour (low birth-weight infants), respectively. Only 12
      respondents (8%) would seek dentist's opinion for all patients with systemic
      diseases related to dental disease. CONCLUSIONS: Medical interns had inadequate
      awareness regarding the systemic effects of periodontal disease. Therefore, an
      integrated teaching of medical and dental sciences is recommended.

PMID- 21731298
TI  - Nocardiosis in a tertiary care hospital in saudi arabia.
AB  - BACKGROUND: Nocardiosis is an uncommon bacterial infection that is caused by
      aerobic actinomycetes of the genus Nocardia. This pathogen has emerged as an
      important cause of mortality and morbidity among both immunocompetent and (more
      commonly) immunocompromised hosts. The prevalence of nocardiosis is unknown in
      Saudi Arabia. Only sporadic cases of cutaneous nocardiosis have been reported. In
      this study, we performed a 10-year retrospective review of all cases of
      nocardiosis identified at the King Fahad National Guard Hospital in Riyadh.
      Clinical presentation, risk factors, site of disease involvement, radiological
      features, and outcomes of 30 patients with pulmonary and disseminated nocardiosis
      are presented. MATERIALS AND METHODS: A retrospective chart review of all cases
      of nocardiosis over the last ten years. RESULTS: Thirty cases of nocardiosis were
      identified. The disease was more common in males. Fever and cough was the most
      common presentation. Most of the patients had an underlying pulmonary disease.
      Consolidation was the most prevalent radiological feature. Pleural effusion was
      common. Unfortunately, none of the isolates were sub-speciated. Cure was possible
      in 40% of the cases. Ten percent of patients died, while follow-up on the rest of
      the patients was lost. CONCLUSION: Nocardiosis is not uncommon in Saudi Arabia.
      Cases are not restricted to the classical immunocompromised host. A database is
      urgently needed to better evaluate the prevalence of the illness among the Saudi
      population.

PMID- 21731299
TI  - Potential activity of the purine compounds caffeine and aminophylline on
      bacteria.
AB  - BACKGROUND: Purine compounds are special types of alkaloids. Caffeine and
      aminophylline are considered the most important members of purines due to their
      wide use in therapeutics. AIMS: To detect any potential antibacterial effects on
      pathogenic bacteria of the widely prescribed members of purines caffeine and
      aminophylline. MATERIALS AND METHODS: Two species of gram-positive bacteria and
      five species of gram-negative bacteria were exposed to these purine agents.
      Antibacterial effects of the tested purines were determined using the
      spectrophotometer method to assess the minimum inhibition concentrations (MIC).
      RESULTS: Among the strains of bacteria tested, Bacillus subtilis showed the most
      susceptibility to purine agents. Staphylococcus aureus and Bacillus subtilis were
      found to be more susceptible to caffeine than the other strains. Aminophylline
      showed inhibitory action on many isolates, especially at the concentration of
      10mg/ml. Paracoccus yeei demonstrated resistance to all tested purine compounds
      up to a concentration of 10.5mg/ml. CONCLUSIONS: Caffeine and aminophylline had
      the ability to inhibit many strains of pathogenic bacteria.

PMID- 21731300
TI  - Antigenic distribution of west nile virus in various organs of wildly infected
      american crows (corvus brachyrhynchos).
AB  - OBJECTIVE: Since its discovery in the western hemisphere in 1999, West Nile virus
      (WNv) has caused extensive bird mortality across North America, especially in
      American crows (Corvus brachyrhynchos) which are highly susceptible to WNv. In
      this study, antigenic distribution of WNv among different organs of American
      crows was studied, using the immunohistochemistry technique (IHC). MATERIALS AND
      METHODS: Dead crows reported by residents were collected, transported on ice, and
      were necropsied for heart, lung, brain, intestine, kidney, liver, spleen,
      pancreas, and gonad tissues. Gross examination was performed on brain, heart,
      lung, liver, kidney, spleen, bursa of fabricius, gastrointestinal tract, skeletal
      muscle, pancreas, reproductive tract, and skin. Gross hemorrhage of brain,
      splenomegaly, meningoencephalitis, myocarditis, and trauma were sporadically
      observed in some of the infected carcasses. Formalin-fixed paraffin-embedded
      tissue sections were stained with IHC technique followed by counter staining with
      hematoxylin and eosin. RESULTS: WNv antigen was detected in brain, spleen, heart,
      kidney, liver, gonads, intestine, lung, and pancreas. The spleen was found to be
      positive in all infected crows, followed by kidney, liver, and duodenum (95%
      each). Heart and pancreas were positive in 63% while brain was positive in 36.5%
      of the infected crows. CONCLUSION: More than one tissue sample is suggested to
      screen WNv infection using IHC technique. IHC has the advantage of correlating
      the visual destruction of tissue architecture with the presence of stained WNv
      antigen but as compared to PCR, IHC has the disadvantage of longer turnaround
      time, which is critical when used as a surveillance tool.

PMID- 21731301
TI  - Tuberculosis: current situation, challenges and overview of its control programs
      in India.
AB  - Tuberculosis (TB) is one of the most ancient diseases of mankind, with molecular
      evidence going back to over 17,000 years. In spite of newer modalities for
      diagnosis and treatment of TB, unfortunately, people are still suffering, and
      worldwide it is among the top 10 killer infectious diseases, second only to HIV.
      According to World Health Organization (WHO), TB is a worldwide pandemic. It is a
      leading cause of death among HIV-infected people. In India, historically
      speaking, fight against TB can be broadly classified into three periods: early
      period, before the discoveries of x-ray and chemotherapy; post-independence
      period, during which nationwide TB control programs were initiated and
      implemented; and the current period, during which the ongoing WHO-assisted TB
      control program is in place. Today, India's DOTS (directly observed treatment
      short course) program is the fastest-expanding and the largest program in the
      world in terms of patients initiated on treatment; and the second largest, in
      terms of population coverage. Major challenges to control TB in India include
      poor primary health-care infrastructure in rural areas of many states;
      unregulated private health care leading to widespread irrational use of first
      line and second-line anti-TB drugs; spreading HIV infection; lack of political
      will; and, above all, corrupt administration. Multidrug-resistant TB (MDR-TB) is
      another emerging threat to TB eradication and is a result of deficient or
      deteriorating TB control program. WHO with its "STOP TB" strategy has given a
      vision to eliminate TB as a public health problem from the face of this earth by
      2050. For this review article, data available at the official websites of WHO;
      and from the Ministry of Health, Government of India, were consulted, and search
      engines PubMed((r)) and Google Scholar((r)) were used.

PMID- 21731302
TI  - River blindness: an old disease on the brink of elimination and control.
AB  - For decades, onchocerciasis (or river blindness) was one of the most common
      infectious causes of blindness in the world. Primarily an infection of Africa,
      with limited distribution in the new world, disease due to the nematode
      Onchocerca volvulus is rapidly diminishing as a result of large public health
      campaigns targeting at risk populations in Africa and the Americas. Existing and
      newly-developed treatment strategies offer the chance to eliminate onchocercal
      ocular morbidity in some parts of the world. This article reviews these treatment
      strategies, current clinical and epidemiologic aspects of onchocerciasis, and the
      next steps toward elimination.

PMID- 21731303
TI  - Cysticercosis control: bringing advances to the field.
AB  - Progress towards Taenia solium control is evident in the development of new
      technologies and in increasing regional coordination, yet disease eradication
      remains unlikely in the near future. In the meantime, translation of research
      advances into functioning control programs is necessary to address the ongoing
      disease burden in endemic areas. Multiple screening assays, effective treatments
      for both human and porcine infection, and vaccines blocking transmission to pigs
      are currently available. Strategies based on identification and treatment of T.
      solium adult tapeworms, as well as interventions that block cysticercosis
      acquisition in pigs have temporarily reduced transmission. Building on these
      successes with controlled community trials in varying endemic scenarios will
      drive progress towards regional elimination.

PMID- 21731304
TI  - Conquering malaria: enhancing the impact of effective interventions towards
      elimination in the diverse and changing epidemiology.
AB  - Malaria remains a major global disease burden causing just under a million deaths
      each year, mainly of children and pregnant women in sub-Saharan Africa. It
      consumes up to 40% of public health expenditure of these poor countries, causing
      in Africa US$ 12 billion in lost GDP every year. This should not be acceptable
      since malaria is preventable, and there is clear evidence that optimal use of
      current tools can reduce much of the suffering and deaths. Three major factors
      allowing this to happen include: (i) inadequate funding to implement a massive
      initial surge, to achieve universal coverage, (ii) weak country capacities for
      rapid scale up of such interventions and little or no use of evidence-guided
      methods, and (iii) insufficient coordination of efforts between national
      programmes, donors and technical agencies in strategic planning for sustaining
      gains and in building capacity. We discuss the importance of the surge and the
      kind of approaches that would accelerate the pace toward elimination and eventual
      eradication.

PMID- 21731305
TI  - Novelties on amoebiasis: a neglected tropical disease.
AB  - In accordance with the 1997 documents of the World Health Organization (WHO),
      amoebiasis is defined as the infection by the protozoan parasite Entamoeba
      histolytica with or without clinical manifestations. The only known natural host
      of E. histolytica is the human with the large intestine as major target organ.
      This parasite has a very simple life cycle in which the infective form is the
      cyst, considered a resistant form of parasite: The asymptomatic cyst passers and
      the intestinal amoebiasis patients are the transmitters; they excrete cysts in
      their feces, which can contaminate food and water sources. E. histolytica sensu
      stricto is the potentially pathogenic species and E. dispar is a commensal non
      pathogenic Entamoeba. Both species are biochemical, immunological and genetically
      distinct. The knowledge of both species with different pathogenic phenotypes
      comes from a large scientific debate during the second half of the 20(th)
      century, which gave place to the rapid development of diagnostics technology
      based on molecular and immunological strategies. During the last ten years,
      knowledge of the new epidemiology of amoebiasis in different geographic endemic
      and non-endemic areas has been obtained by applying mostly molecular techniques.
      In the present work we highlight novelties on human infection and the disease
      that can help the general physician from both endemic and non-endemic countries
      in their medical practice, particularly, now that emigration is undoubtedly a
      global phenomenon that is modifying the previous geography of infectious diseases
      worldwide.

PMID- 21731306
TI  - Prevention of Soil-transmitted Helminth Infection.
AB  - Soil-transmitted helminths (STHs) form one of the most important groups of
      infectious agents and are the cause of serious global health problems. The most
      important STHs are roundworms (Ascaris lumbricoides), whipworms (Trichuris
      trichiura) and hookworms (Necator americanus or Ancylostoma duodenale); on a
      global level, more than a billion people have been infected by at least one
      species of this group of pathogens. This review explores the general concepts of
      transmission dynamics and the environment and intensity of infection and
      morbidity of STHs. The global strategy for the control of soil-transmitted
      helminthiasis is based on (i) regular anthelminthic treatment, (ii) health
      education, (iii) sanitation and personal hygiene and (iv) other means of
      prevention with vaccines and remote sensoring. The reasons for the development of
      a control strategy based on population intervention rather than on individual
      treatment are discussed, as well as the costs of the prevention of STHs, although
      these cannot always be calculated because interventions in health education are
      difficult to measure. An efficient sanitation infrastructure can reduce the
      morbidity of STHs and eliminates the underlying cause of most poverty-related
      diseases and thus supports the economic development of a country.

PMID- 21731307
TI  - Melioidosis: a case report.
AB  - Burkhloderia pseudomallei has recently gained importance as an emerging pathogen
      in India. It causes various clinical manifestations like pneumoniae, septicaemia,
      arthritis, abscess etc. Cases have been reported from Southeast Asia mainly
      Thailand, Malaysia, Vietnam, etc. In India, few cases have been reported mainly
      from the southern part of the country. Patient was a 65-year-old male and
      presented with fever 1 month back, cough and breathlessness for same period,
      swelling on both ankles from 7 days. B. pseudomallei was isolated from
      endotracheal secretions, blood cultures, leg wound. He was successfully treated
      with Imipenem and Doxycycline and put on maintenance therapy now, and is
      currently doing well.

PMID- 21731308
TI  - Outbreak of human buffalopox infection.
AB  - An outbreak of febrile illness with vesicular lesions on hands and forearms of
      six persons was investigated. There was simultaneous outbreak of similar illness
      in buffaloes that were milked by these persons. Buffaloes had lesions on many
      parts of body including udder and teats. Manual milking without gloves exposed
      the persons to the infection. Investigations proved that both the outbreaks were
      due to buffalopox virus infection. Improved dairy practices like wearing gloves
      while milking might help in prevention of spread of infection to other animals
      and humans.

PMID- 21731309
TI  - Cholera in ecuador: current relevance of past lessons learnt.
AB  - This report analyses the trends in the cholera epidemic that hit Ecuador in 1991.
      The study is based on personal experiences and analysis of epidemiological
      databases from the Ministry of Public Health of Ecuador. The number of cases and
      initial attack rates in an immunologically naive population are described by
      province. An analysis of the Andean and coastal cholera patterns of transmission
      are described along with its associated risk factors. The logistical,
      environmental, and socio-cultural risk factors prevalent during the epidemic and
      the control measures implemented are also reviewed. Also, the role of the
      epidemic in the development of the public health and healthcare resources in
      Ecuador is discussed here. Current data indicate favorable conditions for another
      outbreak of cholera in Ecuador. In view of the existing risk factors, new
      strategies are proposed to prevent such an epidemic in the future.

PMID- 21731310
TI  - An Apple-core Lesion in the Colon: An Infectious Etiology.
AB  - Gastrointestinal involvement occurs in about 70% to 90% of histoplasmosis cases
      but is usually not the initial manifestation. We present the case of a 52-yearold
      HIV-positive woman who presented with gastrointestinal symptoms and an apple-core
      lesion on CT scan of the abdomen. The patient had been diagnosed with histoplasma
      colitis eight months earlier and was started on long-term itraconazole therapy.
      However, she prematurely discontinued treatment. A colonoscopy during the present
      hospitalization revealed a 3.5-cm mass, biopsies of which revealed Histoplasma
      capsulatum. In the present report, we discuss the differential diagnosis of apple
      core lesions in the colon and the importance of keeping histoplasmosis on the
      differential diagnosis, especially in endemic areas like the Ohio River valley.
      It is equally important to ensure compliance with treatment of histoplasmosis, as
      well as close follow-up, as progression to colonic obstruction while on medical
      management has been reported.

PMID- 21731311
TI  - Subcutaneous human dirofilariasis due to dirofilaria repens: report of two cases.
AB  - Zoonotic filariasis due to Dirofilaria repens (D. repens) is prevalent in several
      regions of the world. In view of recent rise of human D. repens infections in
      Europe, Africa and Asia, it is considered an emerging zoonosis in these
      continents. Most of the documented cases of human dirofilariasis recorded in
      India had ocular infections, but very few subcutaneous dirofilariasis have been
      reported. We hereby report two cases of subcutaneous human dirofilariasis due to
      D.repens with varied clinical presentations.

PMID- 21731312
TI  - Understanding the clinico-microbiological spectrum of common ear, nose and throat
      infections in sikkim, India.

PMID- 21731313
TI  - Characteristics and management patterns of patients admitted with Fever and
      thrombocytopenia to an acute general medical unit in sri lanka.

PMID- 21731314
TI  - Translation research in molecular disease diagnosis: bridging gap from laboratory
      to practice.

PMID- 21731315
TI  - A case of dengue encephalitis with intracerebral hemorrhage.

PMID- 21731316
TI  - Addressing Residual Challenges of VISION 2020: The Right to Sight.

PMID- 21731317
TI  - A Retrieval System for Patients with Avoidable Blindness Due to Diabetic
      Retinopathy who do not Present for Ophthalmic Assessment in Oman.
AB  - BACKGROUND: Many patients with diabetes do not present for eye examinations,
      foregoing the recommended management for diabetic eye care. Proactive steps are
      being taken in Oman to retrieve defaulters (patients who do not present or "no
      show") with Sight Threatening Diabetic Retinopathy (STDR). We present the
      outcomes of the defaulter retrieval system in five regions of Oman in 2009.
      MATERIALS AND METHODS: Ophthalmologists examine eyes periodically, family
      physicians focus on primary prevention of Diabetic Retinopathy (DR) and medical
      retina specialists manage DR in Oman. A person with proliferative stage of DR
      (PDR) and/or Diabetic Macular Edema (DME) in either eye is considered as STDR and
      is registered at regional hospitals. The eye care staff identify the defaulters
      and the hospital staff help them retrieve the defaulters. The reminder of
      reappointment is sent using the text messages on telephone. The glycemic control
      of STDR cases was also noted in Nizwa Hospital. RESULTS: We registered 654 STDR
      cases, of which 494 (75%) were defaulters. Lack of awareness, transport, absence
      of a decision maker, and fear of laser treatment were the main causes for
      defaulting. We successfully retrieved 328 (66.4%) defaulters. The retrieval rates
      among male and female patients were 51.2% and 82%, respectively. The retrieval
      varied by region. In Nizwa hospital, 114 of 131 STDR cases (85%) had poor
      glycemic control. CONCLUSION: Defaulter retrieval system could help healthcare
      providers to identify and motivate patients with STDR towards better compliance.
      Primary prevention measures among STDR cases were poor and need further focus.

PMID- 21731318
TI  - Overcoming gender inequity in prevention of blindness and visual impairment in
      Africa.
AB  - BACKGROUND: Globally, and in Africa, after adjusting for age, women are about 1.4
      times more likely to be blind than men. While women generally live longer than
      men, the lack of accessibility to and use of services is likely the most
      important reason for excess blindness in women in Africa. AIM: We sought to
      review the literature on vision loss in Africa and summarize the findings related
      to gender equity. MATERIALS AND METHODS: Information from across sub-Saharan
      Africa was collected on the evidence of gender inequity and reasons for this
      inequity. Finally, the results were used to generate suggestions on how gender
      equity could be improved. RESULTS: In all published surveys (except one),
      cataract surgical coverage among women was lower than cataract surgical coverage
      among men. Although data available are limited, similar findings appeared in the
      use of services for other disease conditions, notably, childhood cataract and
      glaucoma. Evidence suggests that a variety of approaches are needed to improve
      the use of eye care services. Three main strategies are needed to address gender
      inequity in vision loss in Africa. First, it is important to address transport
      needs. Second, counseling of patients and family members is required. Finally,
      programs need to put in place pricing systems that make the services affordable
      the population. CONCLUSIONS: VISION 2020 can be achieved in Africa, but
      investment is needed in a variety of strategies that will ensure that eye care
      services are affordable, accessible, and acceptable to women and girls.

PMID- 21731319
TI  - How Can Hospital Programs be Strengthened to Enhance Achievement of VISION 2020
      Objectives?
AB  - The global initiative, "VISION 2020 - The Right to Sight" aims to eliminate
      avoidable blindness by year 2020. Avoidable blindness by definition are those
      conditions for which we already have a treatment or a surgical procedure and
      often a proven strategy to either prevent or cure the condition. Thus, the
      challenge to realize this goal would be designing the right service delivery
      systems specific to the local context, organizing the required resources,
      coordination, and implementing and monitoring these. The key "discipline" that is
      required to ensure successful implementation is "Management." To be holistic,
      such management inputs are required both in a program as well as the hospital
      setting. From a program perspective, the focus will need to be on reaching the
      unreached, ensuring equity, creating an enabling environment, putting in place
      the required infrastructure, including that for developing all cadres of the eye
      care team, and functionally integrating eye care into the general health system
      and other developmental activities. From a hospital perspective, the management
      process should manage the internal and external ecosystems as well as all the
      interfaces to the hospital. It should also put in place systems for ensuring an
      adequate patient flow, high productivity, quality, sustainability, and
      accountability. Since in many countries the notion of management in health care
      or more specifically in eye care is at an early stage or nonexistent, a proactive
      effort is required to build the management capacity quickly through a structured
      process.

PMID- 21731320
TI  - Severe visual impairment and blindness in infants: causes and opportunities for
      control.
AB  - Childhood blindness has an adverse effect on growth, development, social, and
      economic opportunities. Severe visual impairment (SVI) and blindness in infants
      must be detected as early as possible to initiate immediate treatment to prevent
      deep amblyopia. Although difficult, measurement of visual acuity of an infant is
      possible. The causes of SVI and blindness may be prenatal, perinatal, and
      postnatal. Congenital anomalies such as anophthalmos, microphthalmos, coloboma,
      congenital cataract, infantile glaucoma, and neuro-ophthalmic lesions are causes
      of impairment present at birth. Ophthalmia neonatorum, retinopathy of
      prematurity, and cortical visual impairment are acquired during the perinatal
      period. Leukocoria or white pupillary reflex can be cause by congenital cataract,
      persistent hyperplastic primary vitreous, or retinoblastoma. While few medical or
      surgical options are available for congenital anomalies or neuro-ophthalmic
      disorders, many affected infants can still benefit from low vision aids and
      rehabilitation. Ideally, surgery for congenital cataracts should occur within the
      first 4 months of life. Anterior vitrectomy and primary posterior capsulotomy are
      required, followed by aphakic glasses with secondary intraocular lens
      implantation at a later date. The treatment of infantile glaucoma is surgery
      followed by anti-glaucoma medication. Retinopathy of prematurity is a
      proliferation of the retinal vasculature in response to relative hypoxia in a
      premature infant. Screening in the first few weeks of life can prevent blindness.
      Retinoblastoma can be debulked with chemotherapy; however, enucleation may still
      be required. Neonatologists, pediatricians, traditional birth attendants, nurses,
      and ophthalmologists should be sensitive to a parent's complaints of poor vision
      in an infant and ensure adequate follow-up to determine the cause. If required,
      evaluation under anesthesia should be performed, which includes funduscopy,
      refraction, corneal diameter measurement, and measurement of intraocular
      pressure.

PMID- 21731321
TI  - Challenges of trachoma control: an assessment of the situation in northern
      Nigeria.
AB  - Over the last three decades, a lot has been achieved in the control of trachoma
      worldwide. New assessment techniques, effective evidence-based control strategy
      with new methods and drugs, and an aggressive global partnership for the control
      of the disease have evolved. As such the number of people with the disease and
      blindness due to the disease had drastically reduced. Trachoma is now only
      responsible for about 4% of blindness worldwide down from 12% some few decades
      ago. Some countries are on the verge of eliminating the disease as a public
      health problem. Despite these achievements numerous challenges remain for
      achieving trachoma control in endemic communities. This article highlights the
      challenges faced in one of the known trachoma endemic areas - northern Nigeria.
      Aspects on the dearth of complete situational data on trachoma, fragmented
      implementation of the SAFE strategy, community apathy, difficulties faced in
      ensuring safe, and quality lid surgery in the most difficult terrain where the
      disease thrives are discussed here. Other unique challenges like managing
      children with severe trichiasis, curbing the high rate of early-onset recurrence
      of trichiasis after lid rotation surgery and challenges to maintain supply of
      antibiotics and implementation of facial cleanliness and environmental
      improvement components of the control strategy are presented along with the
      learnt experiences and recommendations. These challenges and their remedies are
      likely to be shared by other trachoma endemic areas in Africa.

PMID- 21731322
TI  - Prevalence and causes of blindness and visual impairment in sokoto state,
      Nigeria: baseline data for vision 2020: the right to sight eye care programme.
AB  - PURPOSE: To estimate the prevalence of low vision and blindness, identify the
      causes, and suggest policies for an effective eye care program based on 2005 data
      from Sokoto State, Nigeria. MATERIALS AND METHODS: A stratified two-stage cluster
      sampling method was used to quantify the prevalence of blindness and the causes
      from 4 health zones in Sokoto State. Subjects were evaluated using a magnifying
      loupe, direct ophthalmoscope and torchlight. Data were collected based on the
      World Health Organization prevention of blindness coding for an eye examination.
      Prevalences with 95% confidence intervals (CI) were calculated and surgical
      coverage for causes of blindness was also analyzed. RESULTS: The response rate
      was 91%. The prevalence of bilateral blindness was 1.9% (95% CI: 1.5-2.3%)
      ranging from 1.6% to 2.0% across the four health zones. The prevalence was 2.1%
      (95% CI: 1.6-2.6%) in males and 1.6% (95% CI: 1.1-2.1%) in females. The leading
      cause of bilateral blindness was cataract (51.6%), followed by uncorrected
      aphakia (20.9%) and glaucoma (11%). The prevalence of bilateral operable cataract
      was 1.9% (95% CI: 1.5-2.3%). The cataract surgical coverage (individuals with
      visual acuity <6/60) for the study was lower than the couching coverage (4.4% vs.
      14.9%, respectively). Surgical coverage for trichiasis was 4.4%. The major
      barrier to cataract and glaucoma management was cost. CONCLUSIONS: The prevalence
      of blindness in Sokoto State is high yet the main causes are largely avoidable.
      Barriers can be reduced by appropriate health education regarding the eye care
      program and the provision of integrated, sustainable, affordable and equitable
      services.

PMID- 21731323
TI  - Outcomes of cataract surgeries over 16 years in camps held by Al basar
      international foundation in 38 underdeveloped countries.
AB  - PURPOSE: To evaluate the outcomes of 16 years of eye campaigns in 38 countries in
      Africa, Asia and the Middle East MATERIALS AND METHODS: A descriptive,
      retrospective study using the Al-Basar International Foundation (BIF) records.
      BIF is a non-governmental, non-religious philanthropic organization working in
      the field of the prevention of blindness since 1989. Having its base in Saudi
      Arabia and working mainly in Asia and Africa. Study variables included the causes
      of diminished vision, outcomes of eye surgeries, number of camps, patients
      assessed, surgeries performed, intraocular lenses (IOLs) implanted, spectacles
      distributed, general outcomes of campaigns, and other variables. RESULTS: Between
      the periods of November 1989 and June 2006, BIF conducted 620 eye camps. These
      camps were conducted by ophthalmologists with expertise of working in eye camps
      with limited resources and harsh environmental conditions. Over two million
      people were examined and/or treated, and 186, 765 surgeries were performed.
      Nearly 100,000 IOLs were implanted and more than 140,000 spectacles were
      prescribed and distributed. The majority of these activities (74%) took place in
      Asia and the Middle East. The best corrected visual acuity achieved (BCVA) was
      ranked good (6/6 -6/18) in 59% of patients and borderline (BCVA 6/18 - 6/60) in
      35% and poor (BCVA <6/60) in less than 6% of patients based on World Health
      Organization (WHO) criteria. CONCLUSION: Quality assured eye campaigns held by
      BIF helped the most needy countries and people. Intensive volunteer cataract
      programs and surgeries such as those provided by the BIF add significant support
      to the efforts of the WHO and International Agency for the Prevention of
      Blindness in fighting blindness.

PMID- 21731324
TI  - Clinical and epidemiologic characteristics of severe childhood ocular injuries in
      southern iran.
AB  - PURPOSE: To evaluate the clinical and epidemiological characteristics of children
      with ocular trauma. MATERIALS AND METHODS: We retrospectively reviewed the
      medical records of 278 children (aged 15 years or less) hospitalized with ocular
      injuries and treated as inpatients at a tertiary referral center in Shiraz, Iran,
      from 2005 to 2008. Nominal variables were evaluated with a Chi-square test. A P
      value less than 0.05 indicated statistical significance. RESULTS: The cohort was
      comprised of 205 (74%) males, outnumbering females by a ratio of 2.81/1. The mean
      age was 7.6 +/- 3.96 years. Rural residents comprised 125 (45%) of the cohort.
      Sharp objects caused ocular injury in 211 (76%) cases, and 207 (74%) cases had
      open-globe injuries. The lens was injured in 62 (30%) cases at initial
      examination and 89 (43%) patients according to ultrasound examination (P =
      0.006). Twenty-eight cases (10%) developed post-traumatic endophthalmitis.
      Endophthalmitis was associated with needle injury [odd ratio (OR) = 19.25] and
      presence of intraocular foreign body (OR = 3.48). Visual acuity of patients with
      closed-globe injuries was 20/200 or better on both initial and final
      examinations. Visual acuity of patients with open-globe injuries were in the
      range of light perception to 20/200. CONCLUSIONS: Trauma is an important cause of
      childhood ocular morbidity in southern Iran. Playing with sharp objects is an
      important cause of ocular trauma in children, and most injuries can be prevented
      by careful supervision.

PMID- 21731325
TI  - Prevalence and determinants of glaucoma in citizens of qatar aged 40 years or
      older: a community-based survey.
AB  - BACKGROUND: We present the prevalence and determinants of glaucoma among subjects
      40 years of age and older in Qatar. MATERIALS AND METHODS: This community-based
      survey was held in 2009 at 49 randomly selected clusters. Demographic details and
      history of glaucoma was collected by the nurses. Ophthalmologists evaluated the
      optic disc and retina using a digital camera housed in a mobile van. Visual field
      was tested with an automated perimeter, the intraocular pressure with an
      applanation tonometer and the angle of the anterior chamber by gonioscopy. A
      panel of glaucoma experts diagnosed subjects with glaucoma. RESULTS: This survey
      enrolled 3,149 (97.3%) participants. The age- and sex-adjusted prevalence of
      glaucoma in the population aged 40 years and older was 1.73% (95% confidence
      intervals [CI] 1.69-1.77). Accordingly, 5,641 individuals in this age group in
      Qatar would have glaucoma. Chronological age of 60 years and older (Odds ratio
      [OR] 11.1) and the presence of myopia (OR 1.78) were predictors of glaucoma. Open
      angle glaucoma was diagnosed in 44 (65.7%) individuals with glaucoma. In nine
      (13.4%) and 15 (20.9%) subjects, angle closure glaucoma and other (post
      traumatic, pseudoexfoliation) glaucoma were present. Bilateral blindness (vision
      <3/60) and severe visual impairment (<6/60) were found in four (6%) and three
      (4.5%) subjects with glaucoma, respectively. Glaucoma was treated in 36 (54%)
      subjects. CONCLUSIONS: The prevalence of glaucoma among citizens of Qatar aged 40
      years and older was 1.71%. Glaucoma was associated with the age of 60 years and
      older and the presence of myopia.

PMID- 21731326
TI  - Six year Trend in Cataract Surgical Techniques in Iran.
AB  - PURPOSE: To determine the cataract surgery techniques performed in Iran from 2000
      to 2005. MATERIALS AND METHODS: This study was part of the Iranian Cataract
      Surgery Survey (ICSS) which was a retrospective cross-sectional study. All major
      ocular surgery units and 10% of randomly selected minor units throughout Iran
      were included. Excluding the 2 week Iranian New Year holiday, 1 week per season
      between 2000 and 2005 (a total of 24 weeks) was selected for each center, and
      data on all cataract surgeries performed during these weeks were collected by
      reviewing patient records. The ANOVA repeated measure test was performed to
      determine longitudinal changes with a P<0.05 denoting statistical significance.
      RESULTS: Phacoemulsification with intraocular lens (IOL) implantation has become
      the surgical method of choice in Iran, increasing from less than 7% in 2000 to
      57% in 2005 (P<0.0001). Extracapsular cataract extraction showed a reverse trend
      compared to phacoemulsification, decreasing from greater than 91% in 2000 to 41%
      in 2005 (P<0.0001). Intracapsular cataract extraction and lensectomy were rarely
      performed without significant changes over time (P>0.05). CONCLUSION:
      Phacoemulsification with IOL implantation has become the preferred cataract
      surgery method in Iran during recent years.

PMID- 21731327
TI  - The association between refractive errors and cataract: the tehran eye study.
AB  - PURPOSE: To determine the association between refractive errors and different
      types of cataract in Tehran, Iran. MATERIALS AND METHODS: In a cross-sectional
      survey with a stratified cluster sampling approach, refractive errors were tested
      under cycloplegia. Myopia and hyperopia were defined as a spherical equivalent
      refractive error <-0.5 diopters (D) and more than +0.5 D, respectively. Cataract
      was graded according to the Lens Opacities Classification System III
      classification and the association between refractive errors and cataract was
      assessed. Of 1434 participants over the age of 40 years who participated in the
      study, data from 1313 right eyes were analyzed. RESULTS: The mean age of the
      participants was 52.7 +/- 10.0 years, and 58.3% (n = 767) were female. Overall,
      myopia was more prevalent among those with cataract (odds ratio [OR]: 2.00, 95%
      confidence interval [CI]: 1.38-2.89). Based on the type of cataract and
      refractive errors, the odds of myopia was significantly higher with nuclear
      cataracts (OR: 1.81, 95% CI: 1.14-2.87). The odds of myopia was higher for cases
      of nuclear cataract with some degrees of posterior subcapsular cataract (PSC)
      (OR: 3.33, 95% CI: 1.42-7.80). Of nine participants with cortical cataract, seven
      participants had hyperopia (OR: 3.77, 95% CI: 0.78-18.31). CONCLUSION:
      Individuals with nuclear and PSC showed a significantly higher prevalence of
      myopia while the prevalence of hyperopia was lower in those with cataract. High
      myopia was seen in higher grades of nuclear cataract. The high percentage of
      hyperopia was also significant in patients with cortical cataract. More studies
      are necessary to clarify the correlation between cortical cataract and hyperopia.

PMID- 21731328
TI  - Epidemiology of penetrating eye injury in ibadan: a 10-year hospital-based
      review.
AB  - PURPOSE: To assess risk factors associated with the occurrence of penetrating
      ocular injuries among patients presenting to an eye hospital at Ibadan, Nigeria.
      MATERIALS AND METHODS: All cases of penetrating ocular injury presenting over a
      10 - year period, were identified by retrospective chart review. All current
      cases of penetrating ocular injury identified were included. All information was
      obtained retrospectively from the medical records. RESULTS: The cohort consisted
      of 135 cases. The follow-up was for an average period of 24.6 weeks (range, 12
      312 weeks). Injuries were most likely to occur at home, in a domestic setting
      (58%). The most common mechanism of injury was projectile missiles hitting the
      eye. The age range for injuries was 9 months to 70 years. Penetrating ocular
      injury was most frequent in the 20-29 years group (31.9%) followed by the 0-9
      years age group (31.1%). Males were more frequently involved than females (ratio
      4:1). The final acuity was better than 6/18 in 14.8% and less than 3/60 in 59.3%
      of cases. CONCLUSIONS: Penetrating ocular injury occurs, most frequently, in a
      domestic setting and mostly as a result of working with sharp objects. Preventive
      measures are recommended to reduce visual disabilities due to ocular injuries.

PMID- 21731329
TI  - Ophthalmic research priorities and practices in Nigeria: an assessment of the
      views of nigerian ophthalmologists.
AB  - PURPOSE: To study the views of ophthalmologists on research priorities and
      outcomes in Nigeria. MATERIALS AND METHODS: A structured questionnaire was
      distributed to 120 ophthalmologists and ophthalmic residents who were attending
      an annual congress in Nigeria. The participants' background information, relative
      research priorities, frequency of publications, research types, publication
      media, challenges faced in publishing and impact on health practice or policy
      were collected. RESULTS: Eighty-nine (74.2%) of the 120 questionnaires were
      returned. Childhood blindness was given the highest priority for ophthalmic
      research by 42.9% of the respondents, and genetic studies had the least priority
      (19.8%). About two-thirds of the respondents had either never been involved or
      only involved occasionally in any type of ophthalmic research. Clinical trials
      (13.1%) and basic science studies (12%) were the least-performed types of
      research. About 51% of the respondents indicated that they had never published in
      journals nor did so "occasionally"; only 9% quarterly and 43% published less than
      once a year. They also indicated that their research very rarely resulted in
      change of clinical practice or health policy (20%). CONCLUSIONS: Research works
      conducted by respondents were largely simple low-budget ones that rarely had
      significant impacts and outcomes, including publication. There is a need to
      retrain and emphasize the importance of research during undergraduate and
      postgraduate medical education. Adequate resources and research infrastructure
      should be provided for ophthalmic research in Nigeria.

PMID- 21731330
TI  - Enucleation and evisceration in the palestinian territories.
AB  - PURPOSE: To examine the demographics and indications in patients undergoing eye
      removal at St. John Eye Hospital (SJEH) in Jerusalem, the largest single provider
      of ophthalmic care in the Palestinian Territories. MATERIALS AND METHODS: In this
      retrospective study, medical records were reviewed for patients undergoing
      enucleation or evisceration at SJEH from November 2004 to March 2007. Calculation
      of percentage, mean and median was performed for the demographics, and
      indications for enucleation and evisceration. RESULTS: Thirty-three eyes of 32
      patients were removed during the period under study. Twelve enucleations and 21
      eviscerations were performed. Mean age was 39 years, and 19 patients were male.
      Indications included severe trauma (8 eyes), painful blind eye with (5 eyes) or
      without (9 eyes) infection, and ophthalmic neoplasm (3 eyes). CONCLUSION: The
      incidence of surgical eye removal at SJEH from 2004 to 2007 was around one
      patient per month for a population over three million. This rate appears far
      lower than those reported in previous studies of similar Palestinian populations.
      Prompt access to medical care for Palestinians is required to mitigate ophthalmic
      morbidity. Approximately half of the cases were caused by severe trauma or
      infection, with rubber bullet injuries responsible for 20% of the traumatic
      cases.

PMID- 21731331
TI  - Transition to phacoemulsification at the farabi eye hospital, iran.
AB  - PURPOSE: To provide objective evidence on the transition of cataract surgical
      care at Farabi Eye Hospital, Iran. MATERIALS AND METHODS: Two separate years,
      2003 and 2006, were selected for evaluation. One thousand nine hundred fifty
      seven surgical records of age-related cataract cases were randomly selected and
      reviewed. Three hundred fifty-three patients (405 eyes) in 2006 and 125 patients
      (153 eyes) in 2003 were selected randomly for a follow-up examination. The two
      phases were compared in terms of surgical routines, patient characteristics and
      outcomes for statistical differences. P <0.05 was considered statistically
      significant. RESULTS: The phacoemulsification rate increased from 25% to greater
      than 90% between 2003 and 2006, rates of corneal incisions and use of foldable
      intraocular lenses tripled, administration of general anesthesia dropped from 80%
      to 12%, the outpatient admission rate rose from 5.2% to 71%, 4% vs. 66% of the
      operations were performed by a senior phacoemulsification surgeon and the number
      of advanced surgeons changed from 6% to 38% (all P-values < 0.001). In 2006, more
      patients at the two extremes of age, more patients with poor systemic conditions
      and myopes underwent surgery (all P-values < 0.05); the cataract surgery volume
      increased by 49% and post-operative visual acuity improved (P = 0.03) while
      patient satisfaction was unchanged. CONCLUSION: We objectively documented the
      transition in cataract surgery technique to phacoemulsification at the Farabi Eye
      Hospital in the mid-2000s. This was accompanied by significant expansion of the
      spectrum of cataract surgery candidates and remarkable attainment of surgical
      skill.

PMID- 21731332
TI  - Herpes zoster ophthalmicus: disease spectrum in young adults.
AB  - PURPOSE: To establish the clinical profile of herpes zoster ophthalmicus (HZO) in
      adults younger than 40 years and correlate the clinical manifestation with their
      immune status. MATERIALS AND METHODS: A retrospective chart review was performed
      of patients younger than 40 years who presented with HZO. Data were collected on
      demographics, medical history, clinical presentation, results of serological
      investigations, and visual outcome. RESULTS: The study cohort comprised 18
      subjects with a mean age of 29.7 +/- 6.2 years. Ophthalmic features included lid
      edema, ptosis, cicatricial lid deformities, sclerokeratitis, peripheral
      ulcerative keratitis, neuroparalytic keratitis, keratouveitis with concomitant
      glaucoma, secondary bacterial keratitis and superficial punctate keratitis with
      dry eye, optic neuritis, and trochlear nerve palsy. Eight of 18 (44.4%) subjects
      were found to be positive for Human Immunodeficiency Virus (HIV). Disseminated
      herpetic lesions were seen present in 5 (63%) of these 8 subjects. Postherpetic
      neuralgia was noted in 6 (75%) of 8 HIV-positive subjects and in 1 HIV-negative
      patient. Final visual acuity was 20/40 or better in 90% of the immunocompetent
      subjects and 20/200 or worse in 100% of the HIV-positive subjects. CONCLUSIONS:
      Immunocompetent young adults do present with features of HZO. However, the
      disease spectrum in HIV-negative patients is localized, less severe, and more
      amenable to therapy as compared with young adults with HIV.

PMID- 21731333
TI  - Primary transpupillary thermotherapy of choroidal melanocytic lesions.
AB  - PURPOSE: To evaluate the role of primary transpupillary thermotherapy (TTT) in
      the treatment of choroidal melanocytic lesions. MATERIALS AND METHODS:
      Retrospective chart review of 24 patients (24 eyes) with choroidal melanocytic
      lesions, including 20 choroidal melanoma and four choroidal nevus treated with
      primary TTT. Choroidal nevus cases treated with primary TTT either demonstrated
      risk factors for growth into an early melanoma or had overlying choroidal
      neovascularization. RESULTS: The mean initial tumor basal diameter was 6.6 (3.0
      10.0) mm and the mean initial tumor thickness was 3.0 (1.0-5.0) mm. The mean
      number of TTT sessions was 2.5 (1-6). The mean decrease in tumor thickness was
      1.2 mm (from 3.0 to 1.8 mm) at a mean follow-up of 22.7 (range 3-90) months. On
      the LogMar scale, visual acuity was stable at 1.0. Complications occurred in 50%
      of eyes. The most frequent complications were vitreous hemorrhage [5 patients
      (20.8%)], focal cataract [5 patients (20.8%)], iris atrophy [4 patients (16.6%)]
      and posterior synechia [4 patients (16.6%)]. There was no significant difference
      in the complication rate with respect to tumor thickness >3 mm versus tumor
      thickness <=3 mm and juxtapapillary versus nonjuxtapapillary location (Fisher's
      exact test, P>0.05). Kaplan-Meier curves showed that 9% of eyes develop
      recurrence by 1 year and 27% develop recurrence by 5 years after primary TTT. Two
      eyes (8.3%) were enucleated because of neovascular glaucoma and one eye (4.1%)
      was exenterated because of extraocular tumor recurrence. Globe salvage was
      achieved in 21 patients (87.5%). One patient (4.1%) with extraocular tumor
      recurrence developed liver metastasis and expired. CONCLUSIONS: Although TTT may
      be useful in the treatment of small choroidal melanocytic lesions, the high
      complication and recurrence rates warrant close monitoring of patients after
      primary TTT even when a flat chorioretinal scar has been achieved.

PMID- 21731334
TI  - Supra-Descemet's Fluid Drainage with Simultaneous Air Injection: An Alternative
      Treatment for Descemet's Membrane Detachment.
AB  - In this report, we present an alternative technique to manage Descemet's membrane
      detachment (DMD). We call the technique supra-Descemet's fluid drainage with
      intracameral air injection. Under topical anesthesia, we injected air through the
      stab incision to fill 2/3 of the anterior chamber. Then we inserted the tip of a
      curved 10/0 needle through the corneal surface (entry angle at 45 degrees) into
      the supra-Descemet's area 3 times to drain this fluid. In our method, we neither
      injected expanding gas or viscoelastic nor used a suture. Consequently, there was
      little chance for suture-induced astigmatism or increased intraocular pressure.
      This technique may be considered a relatively safe and simple surgical method for
      the management of postoperative DMD.

PMID- 21731335
TI  - Median facial cleft in amniotic band syndrome.
AB  - Amniotic band syndrome manifests at birth with a variety of malformations ranging
      from constriction ring to defects incompatible to life, in various parts of the
      body. Although some theories have been proposed for the development of this
      syndrome, the exact cause remains unknown. The median facial cleft is an
      extremely rare manifestation of amniotic band syndrome with a relative paucity of
      reports available in the literature. Here, we report one such case.

PMID- 21731336
TI  - Authors' reply.

PMID- 21731337
TI  - Computerized motion sensitivity screening tests.

PMID- 21731338
TI  - Early experience with intravitreal bevacizumab combined with laser treatment for
      retinopathy of prematurity.

PMID- 21731339
TI  - Tooth for truth (The glory of forensic dentistry).

PMID- 21731340
TI  - The various methods and benefits of denture labeling.
AB  - Labeled dentures can be important in identifying the owners in case of an
      accident, loss of memory, states of unconsciousness, being inadvertently
      misplaced on admission to a hospital or, in identifying the bodies of those who
      have died in a calamity. Positive identification through labeled dentures plays a
      key role in forensic scenario. Marking dentures has been considered as an
      important part of forensic dentistry, although no standardized method is
      followed. A number of labeling systems are available and can be broadly separated
      into either surface marking methods or inclusion systems. Each of the commonly
      described techniques is assessed with respect to their strengths and weaknesses.
      The more contemporary methods, though hi-tech, are expensive and may not be
      suitable for all dental practitioners to use. This article reviews the strengths
      and weaknesses of various methods involved in labeling dentures concluding by
      recommending that this valuable topic be included in the dental curriculum in
      India.

PMID- 21731341
TI  - Bioterrorism: Challenges and considerations.
AB  - Bioterrorism, the deliberate, private use of biological agents to harm and
      frighten the people of a state or society, is related to the military use of
      biological, chemical, and nuclear weapons. Attacks with biological agents are
      among the most insidious and breed the greatest fear. Attacks could go undetected
      for a long time, potentially exposing a vast number of people, who are unaware of
      the threat. Dentist's responses to catastrophes have been redefined by
      bioterrorism. Accurate and substantial information given to the public by
      credible public health and medical experts can do much to allay their fears and
      encourage their cooperation and participation in constructive, organized
      community response efforts. The dental profession could potentially play a
      significant role in the emergency response to a major bioterrorism attack.

PMID- 21731342
TI  - Dental DNA fingerprinting in identification of human remains.
AB  - The recent advances in molecular biology have revolutionized all aspects of
      dentistry. DNA, the language of life yields information beyond our imagination,
      both in health or disease. DNA fingerprinting is a tool used to unravel all the
      mysteries associated with the oral cavity and its manifestations during diseased
      conditions. It is being increasingly used in analyzing various scenarios related
      to forensic science. The technical advances in molecular biology have propelled
      the analysis of the DNA into routine usage in crime laboratories for rapid and
      early diagnosis. DNA is an excellent means for identification of unidentified
      human remains. As dental pulp is surrounded by dentin and enamel, which forms
      dental armor, it offers the best source of DNA for reliable genetic type in
      forensic science. This paper summarizes the recent literature on use of this
      technique in identification of unidentified human remains.

PMID- 21731343
TI  - Experimental studies of forensic odontology to aid in the identification process.
AB  - The importance of dental identification is on the increase year after year. With
      the passage of time, the role of forensic odontology has increased as very often
      teeth and dental restorations are the only means of identification. Forensic
      odontology has played a key role in identification of persons in mass disasters
      (aviation, earthquakes, Tsunamis), in crime investigations, in ethnic studies,
      and in identification of decomposed and disfigured bodies like that of drowned
      persons, fire victims, and victims of motor vehicle accidents. The various
      methods employed in forensic odontology include tooth prints, radiographs,
      photographic study, rugoscopy, cheiloscopy and molecular methods. Investigative
      methods applied in forensic odontology are reasonably reliable, yet the
      shortcomings must be accounted for to make it a more meaningful and relevant
      procedure. This paper gives an overview of the various experimental studies to
      aid in the identification processes, discussing their feasibilities and
      limitations in day-to-day practice.

PMID- 21731344
TI  - Use of frontal sinus and nasal septum patterns as an aid in personal
      identification: A digital radiographic pilot study.
AB  - OBJECTIVES: To examine and classify the variations in the pattern of frontal
      sinus and nasal septum as observed on the posterior anterior Cephalometric
      radiographs, and to propose the possible use of the same in personal
      identification. MATERIALS AND METHODS: This study was conducted on 50 individuals
      visiting the department, whose age ranged from 25 to 50 years. The radiographs of
      25 males and 25 females were recorded using a Kodak 8000 C and Dental Imaging
      Software Viewer 6.3.4. Frontal sinus (symmetry and lobulations) and nasal septum
      patterns (deviations) were observed and classified. RESULTS: Frontal sinus
      symmetry was observed in 29 (58%) individuals and asymmetry was observed in 16
      (32%). Frontal sinuses were absent (bilateral aplasia) in two individuals (4%).
      Unilateral aplasia was seen in three individuals (6%). Straight nasal septum was
      seen in 11 (22%), right deviation in 21 (42%), and left deviation in 15 (30%)
      individuals. Sigmoid was seen in one male (2%), reverse sigmoid in one male (2%),
      and other pattern type in one female (2%). Both frontal sinus and nasal septum
      patterns were assessed together for each individual. Out of 50 individuals, 41
      unique combinations of frontal sinus and nasal septum were found. However, there
      were nine individuals whose patterns matched one of the patterns of the 41
      individuals. CONCLUSION: We observed that the frontal sinus and nasal septum
      patterns had considerable individual variation. A combined use of both the
      patterns, as observed on the radiographs, could serve as an adjunct to other
      methods of personal identification.

PMID- 21731345
TI  - Geriatric forensics: A dentist's perspective and contribution to identify
      existence of elder abuse among his patients.
AB  - AIMS AND OBJECTIVES: To identify existence of elder abuse among the patients
      seeking prosthetic rehabilitation of missing teeth. MATERIALS AND METHODS: This
      study was conducted on 300 patients aged 65 years and above. It included 238
      males and 62 females. A questionnaire prepared by a psychologist was used to
      evaluate the patient in various aspects of neglect. RESULTS: The results revealed
      that 40% of the total subjects that were studied were suffering from neglect in
      one way or the other. CONCLUSION: The results conclude that elder negligence was
      highly prevalent in elder patients who report to the dental office seeking oral
      prosthetic rehabilitation.

PMID- 21731346
TI  - Identification of individuals using palatal rugae: Computerized method.
AB  - Identification of individuals is a challenging task in forensic odontology. In
      circumstances where identification of an individual by fingerprint or dental
      record comparison is difficult, the palatal rugae may be considered as an
      alternative source. Palatal rugae have been shown to be highly individualistic
      and it maintains consistency in shape throughout life. AIMS AND OBJECTIVES: The
      present study is conducted to test the efficiency of computerized software in the
      identification of individuals after obtaining digital photographic images of the
      rugae. MATERIALS AND METHODS: The intra oral photographs of 100 individuals were
      taken using a SLR digital camera. The custom made external attachment was
      attached to the camera to standardize all the photographs. A special software was
      designed called the Palatal Rugae Comparison Software (PRCS Version 2.0) to match
      the clinical photographs. Five evaluators including 3 dentists, 1 computer
      professional, and 1 general surgeon were asked to match the rugae pattern using
      the software. The results were recorded along with time taken by each operator to
      match all the photos using software. RESULTS: The software recorded an accuracy
      of 99% in identification of individuals. CONCLUSION: The present study supports
      the fact of individuality of the rugae. Computerized method has given very good
      results to support the individualization of rugae. Through our study, we feel
      that palatal rugae patterns will be of great use in the future of forensic
      odontology.

PMID- 21731347
TI  - Age estimation in 25-45 yrs. old females by physical and radiological methods.
AB  - AIM: The purpose of this study was to estimate the age in living females in the
      later years (25 to 45 years) from general physical features and radiographic
      changes in the sternum and the mandible. MATERIALS AND METHODS: A cross-sectional
      study was conducted on 64 females (32 subjects in each study and control group).
      All the subjects were physically examined for graying of scalp, body, pubic hair,
      and for wrinkling of skin of the forehead, temporal region, and below the eyes. A
      right lateral view of the chest was taken to determine fusion of the components
      of the sternum. Combined Hair Score, Combined Skin Score, and Combined Bone
      Fusion Score were calculated. An orthopantomogram of each patient was traced for
      lower jaw, mandibular canal and teeth, and D(1), D(2), A values were calculated.
      SPSS Software Version 10.1 was used for the execution of the regression command
      on the 32 cases of the control group, whose ages were known. RESULTS: Combined
      skin score, mandible right D(2), mandible right angle, and mandible left angle
      turned out significant in the prediction of age. Using the regression equation
      obtained, the age of the 32 subjects in the study group was estimated. In 9.3% of
      cases, the predicted ages exactly matched the actual ages. A variation of 1-4
      years was seen in 75% of the cases. A variation of 6-7 years was seen in 15.6% of
      the cases. CONCLUSION: This study succeeded in most instances in predicting the
      ages of the study group and in arriving at a formula for age estimation between
      the ages of 25 and 45 years without using any invasive, costly, time - consuming,
      or troublesome method.

PMID- 21731348
TI  - Current trends in forensic genetics.

PMID- 21731349
TI  - 8 national conference of Indian association of forensic odontology.

PMID- 21731350
TI  - Why do we Need Quality Articles, What are we Going to do With?

PMID- 21731351
TI  - Formulation, In Vitro and In Vivo Pharmacokinetics of Anti-HIV Vaginal
      Bioadhesive Gel.
AB  - Inexpensive and female-controlled pre-exposure prophylaxis strategies to prevent
      mucosal transmission of the virus, is urgently needed with the rising prevalence
      of human immunodeficiency virus (HIV-1 and HIV2) infections in women. Zidovudine
      loaded bioadhesive vaginal gel may become one of the very useful strategies, as
      it can be used not only for controlled release but also for enhancing
      bioavailability. Drug delivery through vaginal gel is a promising area for
      continued research with the aim of achieving controlled release with enhanced
      bioavailability over longer periods of time. The aim of the study was to develop
      a newer prolong releasing Zidovudine (AZT) bioadhesive vaginal gel to treat HIV
      infections with increased patient convenience. AZT-loaded bioadhesive vaginal gel
      was prepared successfully by using cold mechanical method. F3 formulation
      containing carbopol-HPMC (1:3) was selected and evaluated in order to achieve
      objectives of this study. In vitro drug release study of F3 showed in 24 h drug
      released following case I Fickian (n <= 0.5) transport mechanism, and in vivo
      drug release was found much better (T(max)), (C(max)), and bioavailability (F)
      comparison with oral pour drug solution. It was also showed good extrudability,
      spreadability, and bioadhesive strength. A generalized protocol, for the further
      research, in this area will surely expected to yield significant outcome with
      improved drug delivery system.

PMID- 21731352
TI  - Multiple unit particles system of ramipril: an approach to enhance stability.
AB  - The present invention relates to produce multiple unit particle system (MUPS) of
      stabilized ramipril pellets, hydrochlorothiazide, diluents, superdisintegrants,
      and lubricants which produce better dissolution of the system for better
      bioavailability with improving stability and bioavailability of ramipril. More
      particularly, the present invention is directed for stabilized ramipril against
      decomposition into degradation products, namely ramipril-DKP and ramipril-diacid,
      during formulation and storage conditions. Simple ramipril formulation shows
      15.15% related impurities after 3-month accelerated stability study, which was
      minimized to the 2.07% related impurities in ramipril pellets after 6 month
      accelerated stability study. By making MUPS of ramipril pellets,
      Hydrochlorothiazide and other excipients show better dissolution (100.4% of
      ramipril and 97.9% of hydrochlorothiazide within 60 min) to produce better
      bioavailability. So, making MUPS containing ramipril pellets with polymer coating
      and hydrochlorothiazide and other excipients shows better stability of ramipril
      along degradation and synergistic effect among hypertension in immediate
      delivery.

PMID- 21731353
TI  - Preparation and in vitro Characterization of Porous Carrier-Based Glipizide
      Floating Microspheres for Gastric Delivery.
AB  - Floating microspheres have been utilized to obtain prolonged and uniform release
      of drug in the stomach for development of once-daily formulations. A controlled
      release system designed to increase residence time in the stomach without contact
      with the mucosa was achieved through the preparation of floating microspheres by
      the emulsion solvent diffusion technique, using (i) calcium silicate (CS) as
      porous carrier; (ii) glipizide, an oral hypoglycemic agent; and (iii)
      Eudragit((r)) S as polymer. The effects of various formulations and process
      variables on the internal and external particle morphology, micromeritic
      properties, in vitro floating behavior, drug loading, and in vitro drug release
      were studied. The microspheres were found to be regular in shape and highly
      porous. The prepared microspheres exhibited prolonged drug release (~8 h) and
      remained buoyant for >10 h. The mean particle size increased and the drug release
      rate decreased at higher polymer concentrations. No significant effect of the
      stirring rate during preparation on drug release was observed. In vitro studies
      demonstrated diffusion-controlled drug release from the microspheres. Microsphere
      formulation CS4, containing 200 mg calcium silicate, showed the best floating
      ability (88% buoyancy) in simulated gastric fluid. The release pattern of
      glipizide in simulated gastric fluid from all floating microspheres followed the
      Higuchi matrix model and the Peppas-Korsmeyer model.

PMID- 21731354
TI  - Encapsulation of naproxen in lipid-based matrix microspheres: characterization
      and release kinetics.
AB  - The objective of this study was to microencapsulate the anti-inflammatory drug
      (naproxen) to provide controlled release and minimizing or eliminating local side
      effect by avoiding the drug release in the upper gastrointestinal track. Naproxen
      was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using
      modified melt dispersion (modified congealable disperse phase encapsulation)
      technique. Effect of various formulation and process variables such as drug-lipid
      ratio, concentration of modifier, concentration of dispersant, stirring speed,
      stirring time, temperature of external phase, on evaluatory parameters such as
      size, entrapment efficiency, and in vitro release of naproxen were studied. The
      microspheres were characterized for particle size, scanning electron microscopy
      (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies,
      for in vitro release kinetics. The shape of microspheres was found to be
      spherical by SEM. The drug entrapment efficiency of various batches of
      microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release
      studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65%
      drug release. In vitro drug release from all the batches showed better fitting
      with the Korsmeyer-Peppas model, indicating the possible mechanism of drug
      release to be by diffusion and erosion of the lipid matrix.

PMID- 21731355
TI  - Taste masking and molecular properties of metformin hydrochloride-indion 234
      complexes.
AB  - Metformin hydrochloride is an oral antidiabetic biguinide agent, used in the
      management of non-insulin-dependent (type-2) diabetes mellitus. The purpose of
      present work was to formulate tasteless complexes of metformin hydrochloride with
      indion 234 and to evaluate molecular properties of drug complexes. The drug
      loading onto ion-exchange resin was optimized for mixing time, activation, effect
      of pH, mode of mixing, ratio of drug to resin, and temperature. Drug resin
      complexes (DRC) were evaluated for taste masking and characterized by x-ray
      diffraction study and infrared spectroscopy. Metformin hydrochloride release from
      DRC is obtained at salivary and gastric pH and in the presence of electrolytes.
      The efficient drug loading was evident in batch process using activated indion
      234 with a pH of 3.5 and drug-resin ratio of 1:1.2, while temperature enhances
      the complexation process. Infrared spectroscopy revealed complexation of -NH
      (drug) with indion 234. DRC are amorphous in nature. Drug release from DRC in
      salivary pH was insufficient to impart bitter taste. Volunteers rated the complex
      as tasteless and agreeable. Complete drug release was observed at gastric pH in 3
      h. The drug release was accelerated in the presence of electrolytes. Indion 234
      is inexpensive, and the simple technique is effective for bitterness masking of
      metformin.

PMID- 21731356
TI  - Investigation of neuropsychopharmacological effects of a polyherbal formulation
      on the learning and memory process in rats.
AB  - OBJECTIVE: To investigate the neuropsychopharmacological effect of a polyherbal
      formulation (PHF) on the learning and memory processes in rats. MATERIALS AND
      METHODS: PHF contains Withania somnifera (Ashwagandha), Nardostachys jatamansi
      (Jatamansi), Rauwolfia serpentina (Sarpagandha), Evolvulus alsinoides
      (Shankhpushpi), Asparagus racemosus (Shatavari), Emblica officinalis (Amalki),
      Mucuna pruriens (Kauch bij extract), Hyoscyamus niger (Khurasani Ajmo), Mineral
      resin (Shilajit), Pearl (Mukta Shukhti Pishti), and coral calcium (Praval
      pishti). Its effect (500 mg / kg, p.o.) on the learning and memory processes was
      tested. The activity of PHF on memory acquisition and retention was studied using
      passive avoidance learning and elevated plus maze model (EPM) in rats. RESULTS:
      The animals treated with PHF showed a significant decrease in transfer latency as
      compared to the control group in EPM. PHF also produced significant improvement
      in passive avoidance acquisition and memory retrieval, as compared to the
      controls and reduced the latency to reach the shock free zone (SFZ) after 24
      hours. CONCLUSION: The PHF produces significant improvement in passive avoidance
      acquisition and memory retrieval in rats, which needs further investigation.

PMID- 21731357
TI  - Preliminary Phytochemical Screening and Antispasmodic Activity of Artemisia
      macrocephala Jacquem.
AB  - The current work describes the antispasmodic action of Artemisia macrocephala,
      which is achieved via blocking of the calcium channels. This explains its
      traditional use as an antispasmodic.The crude methanolic extract of A.
      macrocephala was studied for possible relaxant effect(s) on spontaneous rabbits'
      jejunum preparations. Analytical-grade chemicals were used in the experimental
      protocols. A. macrocephala gave positive tests for flavonoids, saponins,
      glycosides, alkaloids, and terpenes. A. macrocephala caused relaxation of
      spontaneous rabbits' jejunum preparations (n=6) at a dose of 10.0 mg/mL (EC(50) =
      6.95 +/- 0.20 mg/mL; 95% CI: 6.2 to 7.5). Contractions induced by 80 mM potassium
      chloride (KCl) were also relaxed by the A. macrocephala at dose of 10.0 mg/mL.
      Attempting to find an explanation for the possible mode of action, we found that,
      A. macrocephala at concentration of 1.0 mg/mL produced rightward shift in the
      calcium chloride curves, with EC(50) value of -1.65 +/- 0.02 log [Ca(++)] M vs
      control with EC(50) value of -2.44 +/- 0.043 for calcium chloride curves. At a
      concentration of 1.0 mg/mL it could produce 52.4% of the control response at log
      [Ca(++)] M = -1.6. Similarly, verapamil at a concentration of 0.1 MUM produced a
      rightward shift, with EC(50) value of -1.74 +/- 0.026 log [Ca(++)] M (95% CI: 
      1.66 to -1.82; n=6) vs control with EC(50) value of -2.45 +/- 0.05 log [Ca(++)] M
      (95% CI: - 2.23 to -2.91; n=6). The right shift of the EC(50) values is
      justification for the folkloric use of A. macrocephala as an antispasmodic,
      suggesting that the possible mode of action is through calcium channel blockade.

PMID- 21731358
TI  - Antihistaminic effect of Bauhinia racemosa leaves.
AB  - Bauhinia racemosa Lam. (Caesalpiniaceae) leaves have been used in the treatment
      of asthma traditionally and we therefore undertook this study to scientifically
      validate its benefit in asthma using suitable animal models. Antihistaminic
      principles are known to be useful in the treatment of asthma; hence, in the
      present work, the antihistaminic activity of an ethanol extract of B. racemosa
      (at a dose of 50 mg/kg, i.p.) was assessed using clonidine-induced catalepsy and
      haloperidol-induced catalepsy in Swiss albino mice. The results showed that the
      ethanol extract inhibits clonidine-induced catalepsy but there is no effect on
      haloperidol-induced catalepsy. This suggests that the inhibition is through an
      antihistaminic action and that there is no role of dopamine. Hence, we concluded
      that the ethanol extract has significant antihistaminic activity. The polar
      constituents in the ethanol extract of leaves of B. racemosa may be responsible
      for the antihistaminic activity and B. racemosa may therefore have a role in the
      treatment of asthma.

PMID- 21731359
TI  - Synthesis of tryptoline-3-carboxylic Acid derivatives a novel antidiabetic agent.
AB  - The compounds, 2-(methylsulfonyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3
      carboxylic acid (DM3), 2-(phenylsulfonyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4
      b]indole-3-carboxylic acid (DM(4)), and 2-(p-toluenesulfonyl)-1,2,3,4-tetrahydro
      9H-pyrido[3,4-b]indole-3-carboxylic acid (DM(5)) were synthesized by coupling of
      1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid (DM(2)) with
      methanesulfonyl chloride, benzenesulfonyl chloride, and toluenesulfonyl chloride,
      which in turn, was synthesized by dissolving dilute aqueous ammonia with 2-(N
      hydroxy methyl amino)-indol-3-yl-propanoic acid (DM(1)) which is the reaction
      product of l-tryptophan and formalin. All the intermediates and title compounds
      were characterized by physical, chemical, analytical, and spectral data. All the
      title compounds have been screened for in vivo antidiabetic activity in
      streptozotocin-induced diabetic rats, and serum glucose was estimated
      spectrophotometrically at 505 nm by glucose oxidase/peroxidase method. Compound
      DM(5) showed potent antidiabetic activity.

PMID- 21731360
TI  - Documentation and Records: Harmonized GMP Requirements.
AB  - 'If it's not written down, then it didn't happen!' The basic rules in any good
      manufacturing practice (GMP) regulations specify that the pharmaceutical
      manufacturer must maintain proper documentation and records. Documentation helps
      to build up a detailed picture of what a manufacturing function has done in the
      past and what it is doing now and, thus, it provides a basis for planning what it
      is going to do in the future. Regulatory inspectors, during their inspections of
      manufacturing sites, often spend much time examining a company's documents and
      records. Effective documentation enhances the visibility of the quality assurance
      system. In light of above facts, we have made an attempt to harmonize different
      GMP requirements and prepare comprehensive GMP requirements related to
      'documentation and records,' followed by a meticulous review of the most
      influential and frequently referred regulations.

PMID- 21731361
TI  - A perspective for clinical pharmacy curriculum development and validation in
      asian developing nations.
AB  - This perspective is a reflection of the Personal teaching experience of the
      authors. The aim of this perspective is to identify the weaknesses in the
      pharmacy curriculum development in Asian developing nations and to propose a
      methodological approach for curriculum validation. It has been seen that improper
      selection of the course contents were the common limitations found in the
      pharmacy curriculum in developing nations. Furthermore, lack of facilities and
      improper student evaluation system were the other flaws that are acting as a main
      challenge to pharmacy education in developing nations. A systemic way for the
      curriculum designing and validation can be a solution to manage the observed
      deficiencies. Keeping in view this motivation a set of task are defined in the
      form of Pharmacy Curriculum Development and Validation Model (PCDVM) that can be
      a guideline for the pharmacy educators for the evaluation and validation of the
      curriculum. Partial or full implementation of this model will enable the pharmacy
      institutions to deliver quality knowledge to pharmacy students which will further
      contribute to quality health care system in developing countries.

PMID- 21731362
TI  - Regulatory aspects of pharmaceuticals' exports in gulf cooperation council
      countries.
AB  - The Gulf cooperation council (GCC) region is considered as "Emerging market" for
      pharmaceutical export and bilateral trade. The understanding of the regulatory
      requirements of this region can be beneficial for pharmaceutical export. Some
      incidents of the year 2008-09, like recession or economic slowdown in highly well
      off and regulated market of the EU and US, raised the demand for alternate
      destinations for business. The regulations of Gulf countries are encouraging the
      import of quality generic products, which can be good news to the Indian drug
      manufacturers.

PMID- 21731363
TI  - A pilot study to evaluate pharmaceutical pictograms in a multispecialty hospital
      at dehradun.
AB  - Pharmaceutical pictograms have the potential to play an important role in
      optimizing compliance in the illiterate patient population. Pictograms may
      improve warning comprehension for those with visual or literacy difficulties and
      can sometimes be recognized and recalled far better than words. The main purpose
      of this study is to determine whether these pictograms can be effectively
      understood by illiterate patients, who otherwise cannot read the instructions
      given on their prescription order. In this study, 10 pharmaceutical pictograms
      were evaluated in patients attending the outpatient department of the Shri Mahant
      Indresh Hospital, a multispecialty, referral hospital in Dehradun (Uttarakhand).
      Understanding of pictograms by patients before and after interpretation was noted
      and follow-up interpretation was also noted. Results of the study showed that
      prior to explanation, the majority of the patients were unable to interpret the
      pictograms correctly but after explanation of their meaning, interpretation by
      them showed a marked improvement, indicating the need of using pictograms along
      with verbal reinforcement. The study also highlighted poor patient follow-up, a
      major cause of patient non-compliance, often leading to a poor therapeutic
      outcome of the prescribed medication order. Such problems can be taken care of by
      an active participation by healthcare professionals.

PMID- 21731364
TI  - Proper Reporting of Statistical Parameters in Clinical Trials Published in Indian
      Medical Journals. Is Inclusion of Statistician Play any Significant Role?

PMID- 21731365
TI  - Pharmacovigilance: a worldwide master key for drug safety monitoring: some
      additional information.

PMID- 21731366
TI  - Ayurveda for all: 11 action points for 2011.

PMID- 21731367
TI  - Cow urine distillate as bioenhancer.

PMID- 21731368
TI  - A traditional way of rice preparation with particular benefits for Arthritis and
      musculo-skeletal disorders.

PMID- 21731369
TI  - Diet, Ayurveda and interface with biomedicine.

PMID- 21731370
TI  - The Ashtavaidya physicians of Kerala: A tradition in transition.
AB  - This paper presents what we have learned from the Ashtavaidya Ayurveda physicians
      of Kerala regarding the status of their unique medical tradition of Ayurveda in
      the contemporary context. We extensively interviewed several practicing
      Ashtavaidyas for the "Living History of Indian Scientific Traditions" archive, a
      new initiative at the NCBS, Bangalore to study the history of Indian sciences. As
      heirs of a tradition that has adapted and evolved over centuries without
      compromising its fundamental principles, their views on Ayurveda presented here
      represent an important contribution to the current debate on the role of
      traditional medicine in the Indian public health system.

PMID- 21731371
TI  - Pharmacovigilance: Boon for the safety and efficacy of Ayuvedic formulations.
AB  - Pharmacovigilance is a corrective process originating in pharmaco-epidemiology.
      The 1997 Erice Declaration, presented at the World Health Organisation, became
      the basis on which the concept was implemented internationally for conventional
      systems of medicine. The increasing international acceptance of Ayurveda, led
      regulators to implement a similar program for Ayurveda, particularly as some
      medical professionals, scientists and members of the public reported adverse
      reactions after taking Ayurvedic formulations. The World Health Organisation
      therefore persuaded the Department of AYUSH, Ministry of Health and Family
      Welfare, Government of India, to implement a pharmacovigilance program for
      Ayurveda, as a means to ensuring the safety and efficacy of Ayurvedic medicines.
      After a year of due diligence, the pharmacovigilance program was launched
      nationally on 29 September 2008. Since that time, Ayurveda, Siddha and Unani
      medicines have been monitored according to the provisions of a protocol prepared
      by the National Pharmacovigilance Resource Centre, IPGTRA, Jamnagar, and approved
      by Department of AYUSH. The program was reviewed, first, on 21st January 2009 by
      the National Pharmaco-vigilance Consultative Committee for ASU drugs (NPCC-ASU),
      and again, on 15 Feburary, 2010, when an evaluation meeting effectively rubber
      stamped the program. Among the outcomes of these meetings were several
      suggestions of measures to improve the program's efficiency. Recent developments
      include the constitution of pharmacovigilance centers at all Ayurveda Teaching
      institutes and research centers.

PMID- 21731372
TI  - Beyond reverse pharmacology: Mechanism-based screening of Ayurvedic drugs.
AB  - This paper reviews the pharmacology of Indian medicinal plants, starting with the
      historical background of European work on the subject beginning as early as the
      17th century, and tracing its history through the work of Sen and Bose in the
      1930's, and Vakhil's historic 1949 paper on Sarpaghanda. The often crucial role
      of patient feedback in early discoveries is highlighted, as is the time lag
      between proof of pharmacological action and identification of the active
      principle, and subsequent elucidation of mechanism of action. In the case of
      Indian plants in the 20th century this process sometimes took almost 50 years.
      Reserpine and its mechanisms are given in detail, and its current relevance to
      public health discussed. The foundation of present day methods of pharmacology is
      briefly presented so the complexity of methods used to identify properties of
      Ayurveda derived drugs like forskolin and baicalein, and their bioavailability,
      may be better appreciated. Ayurveda derived anti-oxidants and their levels of
      action, immuno-modulators, particularly with respect to the NF-kB pathway and its
      implications for cancer control, are all considered. The example of curcumin
      derived from turmeric is explained in more detail, because of its role in cancer
      prevention. Finally, the paper emphasizes the importance of Ayurveda's concepts
      of rasayana as a form of dietary chemo-prevention; the significance of ahar,
      diet, in Ayurveda's aspiration to prevent disease and restore health thus becomes
      clear. Understood in this light, Ayurveda may transcend pharmacology as a
      treatment paradigm.

PMID- 21731373
TI  - Phytochemical and pharmacological review of Lagenaria sicereria.
AB  - Lagenaria siceraria (Molina) standley (LS) (Family: Cucurbitaceae) is an annual
      herbaceous climbing plant with a long history of traditional medicinal uses in
      many countries, especially in tropical and subtropical regions. Since ancient
      times the climber has been known for its curative properties, and has been
      utilized for treatment of various ailments, including jaundice, diabetes, ulcer,
      piles, colitis, insanity, hypertension, congestive cardiac failure (CCF), and
      skin diseases. Its fruit pulp is used both as an emetic and purgative, and for
      its cooling, diuretic, antibilious, and pectoral properties. Boiled in oil this
      pulp is used to treat rheumatism and insomnia. A wide range of chemical compounds
      including sterols, terpenoids, flavonoids, and saponins have been isolated from
      the species. Its extracts have been found to possess various pharmacological
      activities. Below, we give a comprehensive review of its ethnomedical uses,
      chemical constituents, and pharmacological profile as a medicinal plant.
      Particular attention is given to its analgesic, anti-inflammatory,
      antihyperlipidemic, diuretic, hepatoprotective, anthelmintic, and antibacterial
      effects so that its potential uses in pharmaceutics can be better evaluated.

PMID- 21731374
TI  - Effect of Aloe barbadensis Mill. formulation on Letrozole induced polycystic
      ovarian syndrome rat model.
AB  - This is a preliminary study that explores the efficacy of Aloe vera gel
      formulation as a possible therapeutic agent in the prevention and management of
      polycystic ovary syndrome (PCOS). PCOS is recognized as the most common
      endocrinopathy of women. Increased androgen synthesis, disrupted
      folliculogenesis, and insulin resistance lie at the patho-physiological core of
      PCOS. Current therapy for such a syndrome is use of insulin sensitizers. Large
      randomized clinical trials of metformin as the insulin-sensitizing drug, however,
      suggested that it produces many side effects after prolonged usage. For this
      reason, an alternate therapy would be to use herbs with hypoglycemic potential.
      Aloe barbadensis Mill. (Liliaceae) popularly known as Aloe vera is a well-known
      plant with such properties. The present study evaluated the efficacy of Aloe vera
      gel formulation in a PCOS rat model. Five month old Charles Foster female rats
      were orally fed with letrozole, a non-steroidal aromatase inhibitor, to induce
      PCOS. The rats were then treated orally with the Aloe vera gel formulation (1 ml
      dose daily for 45 days). This restored their estrus cyclicity, glucose
      sensitivity, and steroidogenic activity. Co-treatment of the inductive agent
      (letrozole) with the Aloe vera gel prevented the development of the PCO
      phenotype. Aloe vera gel formulation exerts a protective effect in against the
      PCOS phenotype by restoring the ovarian steroid status, and altering key
      steroidogenic activity. This can be attributed to phyto-components present in the
      extract.

PMID- 21731375
TI  - Evaluation of anticataract potential of Triphala in selenite-induced cataract: In
      vitro and in vivo studies.
AB  - Triphala (TP) is composed of Emblica officinalis, Terminalia chebula, and
      Terminalia belerica. The present study was undertaken to evaluate its
      anticataract potential in vitro and in vivo in a selenite-induced experimental
      model of cataract. In vitro enucleated rat lenses were maintained in organ
      culture containing Dulbecco's Modified Eagles Medium alone or with the addition
      of 100MUM selenite. These served as the normal and control groups, respectively.
      In the test group, the medium was supplemented with selenite and different
      concentrations of TP aqueous extract. The lenses were incubated for 24 h at 37
      degrees C. After incubation, the lenses were processed to estimate reduced
      glutathione (GSH), lipid peroxidation product, and antioxidant enzymes. In vivo
      selenite cataract was induced in 9-day-old rat pups by subcutaneous injection of
      sodium selenite (25 MUmole/kg body weight). The test groups received 25, 50, and
      75 mg/kg of TP intraperitoneally 4 h before the selenite challenge. At the end of
      the study period, the rats' eyes were examined by slit-lamp. TP significantly (P
      < 0.01) restored GSH and decreased malondialdehyde levels. A significant
      restoration in the activities of antioxidant enzymes such as superoxide dismutase
      (P < 0.05), catalase (P < 0.05), glutathione peroxidase (P < 0.05), and
      glutathione-s-transferase (P < 0.005) was observed in the TP-supplemented group
      compared to controls. In vivo TF 25mg/kg developed only 20% nuclear cataract as
      compared to 100% in control. TP prevents or retards experimental selenite-induced
      cataract. This effect may be due to antioxidant activity. Further studies are
      warranted to explore its role in human cataract.

PMID- 21731377
TI  - The Rosenberg European Academy of Ayurveda - Quality in Ayurvedic education in
      German-speaking Europe.

PMID- 21731376
TI  - Antidiarrheal activity of flowers of Ixora Coccinea Linn. in rats.
AB  - Ixora coccinea Linn (Rubiaceae), a small shrub cultivated throughout India, has
      been reported to possess a number of medicinal properties. It has traditionally
      been used for the treatment of diarrhea and dysentery. However the claims of
      Ayurveda have to be validated by suitable experimental models. The present study
      was therefore undertaken to evaluate the effect of aqueous extract of I. coccinea
      for its antidiarrheal potential against several experimental models of diarrhea
      in albino Wistar rats. Here, we report the effects of aqueous extracts of flowers
      of I. coccinea in the castor oil induced diarrhea model. The gastrointestinal
      transit rate was expressed as the percentage of the longest distance traversed by
      charcoal divided by the total length of the small intestine. Weight and volume of
      intestinal content induced by castor oil were studied by the enteropooling
      method. Loperamide was used as a positive control. The plant-extract showed
      significant (P<0.001) inhibitor activity against castor oil induced diarrhea and
      castor oil induced enteropooling in rats at the dose of 400 mg/kg. There was also
      significant reduction in gastrointestinal motility in the charcoal meal test.
      Results obtained in this study substantiate the antidiarrheal effect of the
      aqueous extract and its use by traditional practitioners in the treatment of
      diarrhea.

PMID- 21731378
TI  - The life and times of Professor K. N. Udupa: An outstanding alumnus of Banaras
      Hindu University.

PMID- 21731379
TI  - Ayurveda GCP Guidelines: Need for freedom from RCT ascendancy in favor of whole
      system approach.

PMID- 21731380
TI  - Integrative endeavor for renaissance in Ayurveda.
AB  - Currently western medicine has assumed the central position in mainstream global
      healthcare. Openness to learn from contemporary disciplines of basic sciences,
      application of modern technology and further adoption of the evidence-based
      approach has helped western medicine gain its currently acknowledged position as
      mainstream modern medicine. Modern medicine has further developed forms of
      integrative medicine by developing interfaces with other systems of medicine,
      including traditional, complementary and alternative medicine. However, these
      developments do not seem to address all the problems facing global health care
      caused by overemphasis on pharmaco-therapeutic drug developments. On the other
      hand, Ayurveda which is founded on genuine fundamentals, has the longest
      uninterrupted tradition of healthcare practice, and its holistic approach to
      healthcare management emphasizes disease prevention and health promotion; if it
      opens up to incorporate emerging new knowledge into mainstream Ayurveda, and
      maintains fidelity to Ayurveda fundamentals, it will certainly provide a broad
      based opportunity to address the majority of the problems that have emerged from
      global healthcare requirements. To bring these solutions to bear, however, it
      will be necessary to progress from the present "utilitarian ethos" to a "unifying
      ethos" for realization of medical integration.

PMID- 21731381
TI  - Traditional uses and medicinal potential of Cordyceps sinensis of Sikkim.
AB  - Cordyceps sinensis has been described as a medicine in old Chinese medical books
      and Tibetan medicine. It is a rare combination of a caterpillar and a fungus and
      found at altitudes above 4500m in Sikkim. Traditional healers and local people of
      North Sikkim recommend the mushroom, i.e., Yarsa gumba, Keera jhar (C. sinensis)
      for all diseases either as a single drug or combined with other herbs. The
      present study was undertaken to collect information regarding the traditional
      uses of cordyceps in Sikkim. It was found that most local folk
      healers/traditional healers use cordyceps for the treatment of 21 ailments. A
      modern literature search was carried out to assess whether the curative effects
      are valid or just blind faith of local people. Chemical constituents of cordyceps
      are given and pharmacological and biological studies reviewed. More mechanism
      based and disease-oriented clinical studies are recommended.

PMID- 21731382
TI  - The transformations of disease in expert and lay medical cultures.
AB  - Every culture has rules for translating signs into symptoms, for linking
      symptomatologies to etiologies and interventions, and for using the evidence
      provided by interventions to confirm translations and legitimize outcomes. The
      path a person follows from translation to socially significant outcome
      constitutes his sickness (Allan Young 1982. p. 270).

PMID- 21731383
TI  - Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets.
AB  - AIM OF THE STUDY: Development of standardized, synergistic, safe and effective
      traditional herbal formulations with robust scientific evidence can offer faster
      and more economical alternatives for the treatment of disease. The main objective
      was to develop a method of preparation of guggulkalpa tablets so that the tablets
      meet the criteria of efficacy, stability, and safety. MATERIALS AND METHODS:
      Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul
      and triphala powder, was used as a model drug. Preliminary experiments on
      marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration
      that indicated probable delayed in vivo disintegration. The study involved
      preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet
      granulation, dry granulation, and direct compression method. The tablets were
      evaluated for loss on drying, volatile oil content, % solubility, and steroidal
      content. The tablets were evaluated for performance tests like weight variation,
      disintegration, and hardness. RESULTS: It was observed that triphalaguggulkalpa
      tablets, prepared by direct compression method, complied with the hardness and
      disintegration tests, whereas tablets prepared by Ayurvedic text methods failed.
      CONCLUSION: Direct compression is the best method of preparing
      triphalaguggulkalpa tablets.

PMID- 21731384
TI  - Clinical evaluation of efficacy of Majoon Ushba and Roghane Hindi in the
      management of psoriasis: A randomized single-blind, placebo-controlled study.
AB  - Psoriasis is a common dermatological disease affecting up to 1-2% of the world's
      population. It is associated with both organic and psychosocial complications
      like psoriatic arthropathy, nephritis, infection, hyperuricemia, hypoproteinemia,
      depression, and stress, and is responsible for hindering patients' daily
      activities. The present study was conducted to assess the safety and efficacy of
      two pharmacopeial Unani formulations (Majoon Ushba and Roghane Hindi) in the
      management of psoriasis on scientific parameters. Thirty diagnosed psoriasis
      patients, satisfying the inclusion criteria, were selected for a randomized,
      single-blind, placebo-controlled study in the Department of Moalajat (Medicine),
      National Institute of Unani Medicine, Bangalore. The patients were divided by the
      method of Random Table Numbers into test and control groups after obtaining
      informed consent. The experimental group comprised 20 patients to whom Majoon
      Ushba 5 g was administered orally twice daily and Roghane Hindi was applied
      locally twice daily. The control group comprised 10 patients who were given
      placebo drugs orally and topically. The duration of the trial was 8 weeks and
      follow-up was done fortnightly. The severity of psoriasis and efficacy of the
      drug was assessed by the Psoriasis Area and Severity Index (PASI) Scale. The
      results of both groups were compared and analyzed statistically. The study showed
      significant reduction in the PASI score in the test group (P < 0.01) as compared
      to placebo. No obnoxious side effects were observed in the test group:
      toxicological parameters were within normal limits even after 2 months of
      treatment. It was therefore concluded that Majoon Ushba and Roghane Hindi are
      safe and effective in the management of psoriasis.

PMID- 21731385
TI  - A true plural being - A life profile of P. R. Krishna Kumar.

PMID- 21731386
TI  - Mimansa.
AB  - This paper considers the relevance to Ayurvedic education of Mimansa, one of the
      six "orthodox" systems of ancient Indian philosophy, which, like Ayurveda, regard
      the Vedas as supremely authoritative. At the postgraduate level, Mimansa assists
      the study of Ayurveda because it provides a system of resolving possible
      conflicts between statements in the texts of the Veda, which can also be applied
      to Ayurveda, when its own methodology of interpretation given in Tantrayukti
      falls short. Indeed, certain commentaries on the Ayurvedic texts are suggestive
      of the Mimansa perspective. The article provides illustrations of this from the
      courses taught at the Institute of Research in Ayurvedic Medicine, Jnana
      Prabhodini, indicating some details of the courses taught, and recounting
      feedback from the students. These show that a course in Mimansa has a useful role
      to play in encouraging students' independent reading of the Ayurvedic texts and
      in maturing their own interpretations of sections that seem obscure.

PMID- 21731387
TI  - Prophylactic measures.

PMID- 21731388
TI  - Anti-ulcerogenic and in vitro antioxidant activities of Lagenaria breviflora (LB)
      whole fruit ethanolic extract in laboratory animals.
AB  - BACKGROUND: The present study was undertaken to evaluate the anti-ulcer and
      antioxidant activities of the ethanol extract of Lagenaria breviflora (EELB)
      whole fruit in laboratory rats. METHODS: The anti-ulcer property of the ethanolic
      extract of the whole fruit of Lagenaria breviflora (LB) was assessed using the
      cold-restraint stress-induced (CRU) gastric ulcer, pyloric ligation-induced (PL)
      gastric ulcer, aspirin-induced (ASP) gastric ulcer and alcohol-induced (AL)
      gastric ulcer models. The scavenging activity of the LB extract was examined with
      1, 1-diphenyl-2-picryl-hydrazyl (DPPH), Nitric oxide, Hydroxyl radical and
      Superoxide anion scavenging models. RESULTS: EELB (50, 100, 150 and 200 mg/kg,
      b.w.) protected against the CRU gastric ulcer dose dependently. Similarly, 150
      mg/kg b.w. of the LB extract protected against the PL gastric ulcer, ASP gastric
      ulcer and AL gastric ulcer and was comparable to omeprazole (10 mg/kg b.w.) or
      Suscralfate (500 mg/kg b.w.), respectively. The in vitro antioxidant activity of
      LB was demonstrated by its ability to quench free radicals generated by nitric
      oxide and superoxide anion with a concomitant scavenging potential against DPPH
      induced radical formation. CONCLUSION: Taken together, the study showed that the
      whole fruit extract possess potent anti-ulcer and antioxidant activities.

PMID- 21731389
TI  - In vitro antiproliferativeactivity of Annona reticulata roots on human cancer
      cell lines.
AB  - BACKGROUND: The phytochemical and pharmacological activities of Annona reticulata
      components suggest a wide range of clinical application in lieu of cancer
      chemotherapy. MATERIALS AND METHODS: Ethanol and aqueous extracts of roots of
      Annona reticulata Linn were studied for their in vitro antiproliferative activity
      on A-549 (human lung carcinoma), K-562 (human chronic myelogenous leukemia bone
      marrow), HeLa (human cervix) and MDA-MB (human adenocarcinoma mammary gland)
      cancer cell lines by MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide] colorimetric assay. RESULTS: The ethanol extract exhibited a prominent
      inhibitory effect against A-549, K-562, HeLa and MDA-MB human cancer cell lines
      at a concentration range between 10 and 40 MUg/ml, whereas the aqueous extract
      showed a lower activity at the same concentration. Simultaneously, the effect of
      the ethanol extract toward the inhibition of Vero cell line proliferation was
      lower in comparison with the cancer cell lines. CONCLUSION: The significant
      antiproliferative activity of the ethanol extract of Annona reticulata roots
      against A-549, K-562, HeLa and MDA-MB human cancer cell lines may be attributed
      toward the collective presence of acetogenins, alkaloids and lower inhibitory
      effect on Vero cell line, which suggests Annona reticulata be used as a
      chemopreventive agent in cancer therapy.

PMID- 21731390
TI  - Hepatoprotective activity of Ocimum sanctum alcoholic leaf extract against
      paracetamol-induced liver damage in Albino rats.
AB  - BACKGROUND: There is a lack of reliable hepatoprotective drugs in modern medicine
      to prevent and treat drug-induced liver damage. Leaves of Sacred/Holy Basil, i.e.
      Green Tulsi (Ocimum sanctum), belonging to family Lamiaceae are used
      traditionally for their hepatoprotective effect. We wanted to evaluate the
      hepatoprotective activity of Ocimum sanctum and observe whether synergistic
      hepatoprotection exists with silymarin. MATERIALS AND METHODS: Albino rats (150
      200 g) were divided into five groups. Groups A and B were normal and experimental
      controls, respectively. Groups C, D and E received the alcoholic extract of
      Ocimum Sanctum leaves (OSE) 200 mg/kg BW/day, silymarin 100 mg/kg BW/day and OSE
      100 mg/kg BW/day + silymarin 50 mg/kg BW/day p.o., respectively, for 10 days.
      Hepatotoxicity was induced in Groups B, C, D and E on the eighth day with
      paracetamol 2 g/kg BW/day. The hepatoprotective effect was evaluated by
      performing an assay of the serum proteins, albumin globulin ratio, alkaline
      phosphatase, transaminases and liver histopathology. The assay results were
      presented as mean and standard error of mean (SEM) for each group. The study
      group was compared with the control group by one-way ANOVA, followed by
      Bonferoni's test. A P-value of <0.01 was considered significant. RESULTS: In
      groups C, D and E, liver enzymes and albumin globulin ratio were significantly (P
      < 0.01) closer to normal than in group B. Reduction in sinusoidal congestion,
      cloudy swelling and fatty changes and regenerative areas of the liver were
      observed on histopathological examination in groups C, D and E, whereas group B
      showed only hepatic necrosis. CONCLUSION: The Ocimum sanctum alcoholic leaf
      extract shows significant hepatoprotective activity and synergism with silymarin.

PMID- 21731391
TI  - Mining of simple sequence repeats in the Genome of Gentianaceae.
AB  - Simple sequence repeats (SSRs) or short tandem repeats are short repeat motifs
      that show high level of length polymorphism due to insertion or deletion
      mutations of one or more repeat types. Here, we present the detection and
      abundance of microsatellites or SSRs in nucleotide sequences of Gentianaceae
      family. A total of 545 SSRs were mined in 4698 nucleotide sequences downloaded
      from the National Center for Biotechnology Information (NCBI). Among the SSR
      sequences, the frequency of repeat type was about 429 -mono repeats, 99 -di
      repeats, 15 -tri repeats, and 2 --hexa repeats. Mononucleotide repeats were found
      to be abundant repeat types, about 78%, followed by dinucleotide repeats (18.16%)
      among the SSR sequences. An attempt was made to design primer pairs for 545
      identified SSRs but these were found only for 169 sequences.

PMID- 21731392
TI  - The study of aqueous extract of Ficus religiosa Linn. on cytokine TNF-alpha in
      type 2 diabetic rats.
AB  - BACKGROUND: Chronic systemic inflammation is an early process in pathogenesis of
      type 2 diabetes. Hence the present study was aimed to investigate the effect of
      traditionally known plant Ficus religiosa on elevated glucose and inflammatory
      marker namely tumor necrosis factor (TNF)-alpha in type 2 diabetic rats. METHODS:
      Type 2 diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in
      neonatal rat model. Aqueous extract of F. religiosa at a dose of 100 and 200
      mg/kg was given orally to desired group of animals for a period of 4 weeks. After
      4 weeks of drug treatment, parameters such as fasting blood glucose, postprandial
      blood glucose and TNF-alpha in serum were analyzed. RESULTS: Aqueous extract of
      F. religiosa at both dose levels i.e., 100 and 200 mg/kg decreased the elevated
      glucose and TNF-alpha in type 2 diabetic rats. The extract at 200 mg/kg had more
      pronounced effect. CONCLUSION: Modulation of cytokine TNF-alpha by the aqueous
      extract of F. religiosa indicates that the anti-inflammatory and immunomodulatory
      property of the plant is related with its potential anti-diabetic activity.

PMID- 21731393
TI  - Colon-targeted quercetin delivery using natural polymer to enhance its
      bioavailability.
AB  - The aim of the present study is to develop a polymer (Guar Gum)-based matrix
      tablet (using quercetin as a model drug) with sufficient mechanical strength, and
      promising in vitro mouth-to-colon release profile. By definition, an oral colonic
      delivery system should retard drug release in the stomach and small intestine,
      and allow complete release in the colon. By drug delivery to the colon would
      therefore ensure direct treatment at the disease site, lower dosing, and fewer
      systemic side effects. Quercetin is antioxidant in nature and used to treat colon
      cancer, but they have poor absorption in the upper part of the gastrointestinal
      tract (GIT). As a site for drug delivery, the colon offers a near neutral pH,
      reduced digestive enzymatic activity, a long transit time, and an increased
      responsiveness to absorption enhancers. By achieving a colon-targeted drug
      delivery system, the absorption of quercetin may be increased, which leads to
      better bioactivity in fewer doses.

PMID- 21731394
TI  - Evaluation of acute toxicity and hepatoprotective activity of the methanolic
      extract of Dichrostachys cinerea (Wight and Arn.) leaves.
AB  - BACKGROUND: D. cinerea are the chief source of drug compounds that are active
      against various ailments such as jaundice, inflammations rheumatism, fever,
      asthma, body ache, chest problems, toothache, ulcers, wounds, eye diseases and
      have an aphrodisiac property. In present study, It was aimed to test the
      hepatoprotective activity of the plant. MATERIAL AND METHODS: The methanolic
      extract of Dichrostachys cinerea (Mimoseae) leaves was subjected to evaluation of
      acute toxicity and hepatoprotective property, using albino mice and rats. The
      parameters for estimation of liver function, based on serum markers such as total
      bilirubin, total protein, alanine aminotransferase, aspartate aminotransferase,
      alkaline phosphatase with histopathological profile of the liver tissue, were
      studied consequently. RESULTS: The methanolic extract did not show any mortality
      up to a dose of 3500 mg/kg body weight. The methanolic extract showed significant
      hepatoprotectivity. The histopathological profile of the drug-treated liver
      tissue demonstrated similar morphology as that of controls. CONCLUSIONS:
      Methanolic extract of Dichrostachys cinerea was found to have significant
      hepatoprotective activity.

PMID- 21731395
TI  - Partial in vitro and in vivo red scorpion venom neutralization activity of
      Andrographis paniculata.
AB  - OBJECTIVE: Red scorpion (Mesobuthus tamulus) is the most lethal among all
      poisonous species of scorpions. Envenoming by Mesobuthus tamulus is quite common
      along the western coast of India, without any established therapy. Andrographis
      paniculata is one of the plants that has long been used in traditional herbal
      medicine for the treatment of poisoning by animal bites. Hence, the study was
      planned to evaluate the ethanolic extract of Andrographis paniculata for the
      treatment of Mesobuthus tamulus envenoming. MATERIALS AND METHODS: Ethanolic
      extract of the plant Andrographis paniculata was obtained using a soxhelet
      apparatus. Lyophilized venom sample of Mesobuthus tamulus was used. Swiss albino
      mice weighing 20-30 g were used in the study. Calculation of LD(99) of Mesobuthus
      tamulus venom was performed using Turner's method. Acute toxicity of Mesobuthus
      tamulus venom and its neutralization by the plant extract at a dose of 1 g/kg and
      2 g/kg in vivo was seen. Neutralization of the lethal venom effect of Mesobuthus
      tamulus by plant extract at the dose of 1 g/kg and 2 g/kg by Alam and Gome's
      method (in vitro) was also seen. RESULTS: The LD(99) of Mesobuthus tamulus venom
      from this study was determined to be 25.12 MUg/g and the LD(50) was 15.85 MUg/g.
      In the acute toxicity and in vivo neutralization study, plant extract at the dose
      of 1 g/kg and 2 g/kg resulted in a mean survival of 62.667 min and 39.333 min,
      respectively. Neutralization of the lethal venom effect of Mesobuthus tamulus by
      the plant extract at the dose of 1 g/kg and 2 g/kg by Alam and Gome's method (in
      vitro) showed a mean survival of 49.667 min and 42.5 min, respectively.
      CONCLUSION: The ethanolic extract of Adrographis paniculata has some protective
      effect against the red scorpion venom in mice but does not offer any survival
      benefit.

PMID- 21731396
TI  - Standardization of some herbal antidiabetic drugs in polyherbal formulation.
AB  - BACKGROUND: Ayurvedic formulations are used to treat a wide variety of diseases
      including diabetes mellitus Standardization of herbal formulation is essential in
      order to assess the quality of drugs. The present paper reports standardization
      of eight herbal anti-diabetic drugs-Momordica charantia (seeds), Syzigium cumini
      (seeds), Trigonella foenum (seeds), Azadirachta indica (leaves), Emblica offi
      cinalis (fruits), Curcuma longa (rhizomes), Gymnema sylvestre (leaves),
      Pterocarpus marsupium (heart-wood) individually and in polyherbal marketed
      samples of Baidyanath Madhumehari Churna MATERIAL AND METHODS: Shivayu Madhuhari
      Churna, Meghdut Madhushoonya Churna and were compared to the in-house preparation
      for physicochemical properties. RESULTS AND CONCLUSIONS: The limits obtained from
      the different physicochemical parameters of the individual eight herbal drugs and
      the marketed formulations could be used as reference standard for standardization
      of the anti-diabetic drugs in a quality control laboratory.

PMID- 21731397
TI  - Analgesic activity and acute toxicity study of Semecarpus anacardium stem bark
      extracts using mice.
AB  - BACKGROUND: The analgesic activity of petroleum ether, chloroform and methanol
      extracts of Semecarpus anacardium was investigated by tail flicking and writhing
      method using acetyl salicylic acid as the standard reference. MATERIALS AND
      METHODS: The staircase method was adopted for the determination of the acute
      toxicity. LD(50) of the petroleum ether extract and the chloroform extract was
      700 mg/kg; however, the LD(50) for the methanol extract was 500 mg/kg. After 1 h
      of oral administration of the extracts, 0.6% acetic acid was administered
      intraperitoneally and the analgesic activity was evaluated. RESULTS: The number
      of writhing observed in the control group was 73.33 writhes. The methanol extract
      showed a significant analgesic activity, with 28.33 writhes, than the petroleum
      ether extract and the chloroform extract. But, all the extracts showed proved to
      be less potent than the standard drug which showed 2.33 writhes. Animals
      pretreated with saline did not show a signify cant effect on the latent period of
      tail-flick response. The analgesic effect of the petroleum ether extract was
      comparatively less evident. The maximum possible analgesia (MPA) increased up to
      9.1% which remained elevated above the basal levels throughout the observation
      period. The MPA calculated for the chloroform extract increased to 14.03%.
      However, the analgesic effect of the methanol extract was also observed at 0.5 h
      following oral administration and the effect remained significant throughout the
      3 h observation period, and was increased to 20.43%. CONCLUSION: Consistent
      analgesic activity of all the three S. anacardium extracts was observed by both
      the methods. The methanol extract was more potent than the petroleum ether and
      chloroform extracts but was less effective than the standard drug. This
      investigation supported the ethnomedicinal claims of S. anacardium.

PMID- 21731398
TI  - Effect of methanolic extract of Lagenaria siceraria (Molina) Standley fruits on
      marble-burying behavior in mice: Implications for obsessive-compulsive disorder.
AB  - CONTEXT: Obsessive-compulsive disorder (OCD) is the fourth most common mental
      disorder and is diagnosed nearly as often as asthma and diabetes mellitus. Over
      the last decade, the inhibition of burying of glass marbles by mice has been used
      as an index of anti-OCD drug action in the so-called marble-burying test.
      Lagenaria siceraria (Molina) Standley (LS), commonly known as "bottle gourd"
      (English), possesses several medicinal properties; little is known about its
      action as a nerve tonic. OBJECTIVE: The purpose of this study was to characterize
      the anti-OCD (anti-compulsive) activity of the methanolic extract of the fruits
      of L. siceraria (Molina) Standley (LS) using the marble-burying behavior in mice.
      MATERIALS AND METHODS: The experiment was conducted in specific animal models of
      Swiss albino mice to evaluate marble-burying behavior. RESULTS AND CONCLUSIONS:
      Intraperitonial administration of 25 and 50 mg/kg of LS extract significantly (P
      < 0.001) decreased the total number of buried marbles. The effect was comparable
      to that of the fluoxetine (10 mg/kg, i.p.). Fluoxetine and LS fruit extract do
      not produce any overt motor dysfunction. Preliminary phytochemical screening of
      the methanolic extract of LS showed the presence of flavonoids, saponins,
      sterols, proteins, tannins and carbohydrates. The results of the study for the
      first time show that the plant possesses anti-compulsive (anti-OCD) activity,
      confirming the traditional claims. Future research should focus on the
      identification and the mechanism of action of the constituents from this plant.

PMID- 21731399
TI  - Antihyperglycemic effect of the alcoholic seed extract of Swietenia macrophylla
      on streptozotocin-diabetic rats.
AB  - BACKGROUND: Streptozotocin (STZ) selectively destroys the pancreatic insulin
      secreting cells, leaving less active cells and resulting in a diabetic state. The
      present study was designed to investigate the antihyperglycemic effect of the
      ethanolic seed extract of Swietenia macrophylla (SME) in normal and STZ-diabetic
      rats. MATERIALS AND METHODS: The experimental groups were rendered diabetic by
      intraperitoneal injection of a single dose of STZ (40 mg/kg body weight [BW]).
      Rats with glucose levels > 200 mg/dL were considered diabetic and were divided
      into 5 groups. Three groups of diabetic animals were orally administered, daily
      with seed extract at a dosage of 50, 100, and 200 mg/kg BW. One group of STZ rats
      was treated as diabetic control and the other group was orally administered 600
      MUg/kg BW glibenclamide daily. RESULTS: Graded doses of seed extract and
      glibenclamide showed a significant reduction in blood glucose levels and
      improvement in serum insulin levels. The extract also improved body weight and
      promoted liver glycogen content. After treatment, hemoglobin (Hb) level increased
      and glycosylated Hb level significantly decreased in diabetic rats. The
      activities of the carbohydrate metabolic enzymes showed significant changes in
      the rats. Of the 3 doses, 100 mg dose showed maximum activity. Histological
      investigations of pancreas also supported the biochemical findings. CONCLUSIONS:
      Thus, our findings indicate the folklore use of the seed for diabetes and the
      mechanism seems to be insulin secretion.

PMID- 21731400
TI  - Verification of the performance accuracy of a real-time skin-dose tracking system
      for interventional fluoroscopic procedures.
AB  - A tracking system has been developed to provide real-time feedback of skin dose
      and dose rate during interventional fluoroscopic procedures. The dose tracking
      system (DTS) calculates the radiation dose rate to the patient's skin using the
      exposure technique parameters and exposure geometry obtained from the x-ray
      imaging system digital network (Toshiba Infinix) and presents the cumulative
      results in a color mapping on a 3D graphic of the patient. We performed a number
      of tests to verify the accuracy of the dose representation of this system. These
      tests included comparison of system-calculated dose-rate values with ionization
      chamber (6 cc PTW) measured values with change in kVp, beam filter, field size,
      source-to-skin distance and beam angulation. To simulate a cardiac
      catheterization procedure, the ionization chamber was also placed at various
      positions on an Alderson Rando torso phantom and the dose agreement compared for
      a range of projection angles with the heart at isocenter. To assess the accuracy
      of the dose distribution representation, Gafchromic film (XR-RV3, ISP) was
      exposed with the beam at different locations. The DTS and film distributions were
      compared and excellent visual agreement was obtained within the cm-sized surface
      elements used for the patient graphic. The dose (rate) values agreed within about
      10% for the range of variables tested. Correction factors could be applied to
      obtain even closer agreement since the variable values are known in real-time.
      The DTS provides skin-dose values and dose mapping with sufficient accuracy for
      use in monitoring diagnostic and interventional x-ray procedures.

PMID- 21731401
TI  - Measuring the presampled MTF from a reduced number of flat-field images using the
      Noise Response (NR) method.
AB  - We evaluate a new method for measuring the presampled modulation transfer
      function (MTF) using the noise power spectrum (NPS) obtained from a few flat
      field images acquired at one exposure level. The NPS is the sum of structure,
      quantum, and additive instrumentation noise, which are proportional to exposure
      squared, exposure, and a constant, respectively, with the spatial-frequency
      dependence of the quantum noise depending partly on the detector MTF. Cascaded
      linear-systems theory was used to derive an exact and generic relationship that
      was used to isolate noise terms and enable determination of the MTF directly from
      the noise response, thereby circumventing the need for precision test objects
      (slit, edge, etc.) as required by standard techniques. Isolation of the quantum
      NPS by fitting the total NPS versus exposure obtained using 30 flat-field images
      each at six or more different exposure levels with a linear regression provides
      highly accurate MTFs. A subset of these images from indirect digital detectors
      was used to investigate the accuracy of measuring the MTF from 30 or fewer flat
      field images obtained at a single exposure level. Analyzing as few as two images
      acquired at a single exposure resulted in no observable systematic error.
      Increasing the number of images analyzed resulted in an increase in accuracy.
      Fifteen images provided comparable accuracy with the most rigorous slope
      approach, with less than 5% variability, suggesting additional image acquisitions
      may be unnecessary. Reducing the number of images acquired for the noise response
      method further simplifies and facilitates routine MTF measurements.

PMID- 21731402
TI  - Maleimide Functionalized Poly(epsilon-caprolactone)-b-poly(ethylene glycol) (PCL
      PEG-MAL): Synthesis, Nanoparticle Formation, and Thiol Conjugation.
AB  - Carboxylic acid terminated poly(epsilon-caprolactone)s (PCL-COOHs) with narrow
      polydispersity were synthesized and coupled with poly(ethylene glycol) (HO-PEG
      OH) to afford PCL-PEG-OH copolymers. The hydroxyl groups in the PCL-PEG-OHs were
      then converted to maleimide groups to afford maleimide terminated PCL-PEG-MALs
      that contained 70-90% maleimide functionality. Nanoparticles with maleimide
      functionality on their surfaces were prepared by impingement mixing. Particle
      sizes and size distributions were determined by dynamic light scattering.
      Conjugation of reduced glutathione with model maleimides and two MAL-functional
      nanoparticles was also demonstrated. The amount of accessible maleimide on the
      particle surface was measured using Ellman's reagent to range between ~51-67%.

PMID- 21731403
TI  - Soliton Thulium-Doped Fiber Laser With Carbon Nanotube Saturable Absorber.
AB  - We report stabilization of a thulium-holmium codoped fiber soliton laser with a
      saturable absorber based on carbon nanotubes. The laser generates transform
      limited 750-fs pulses with 0.5-nJ energy.

PMID- 21731404
TI  - Idiopathic Adrenal Hemorrhage in a Patient with Gestational Trophoblastic
      Neoplasia.
AB  - BACKGROUND: Idiopathic unilateral adrenal hemorrhage is rare. Described is the
      first case reported in the setting of nonmetastatic gestational trophoblastic
      neoplasia. CASE: A primigravida presented with abdominal pain, fever, and a right
      upper quadrant mass during the workup for gestational trophoblastic neoplasia.
      She was diagnosed with idiopathic unilateral adrenal hemorrhage. She was treated
      with surgical resection and single-agent chemotherapy and had complete remission.
      CONCLUSIONS: Idiopathic unilateral adrenal hemorrhage is a rare condition and
      must be considered in the presentation of abdominal pain, fever, and an abdominal
      mass.

PMID- 21731405
TI  - Mental health of lesbian, gay, and bisexual youth: A developmental resiliency
      perspective.
AB  - Research suggests that lesbian, gay, and bisexual (LGB) youth are at increased
      risk for both victimization and internalizing mental health problems, but limited
      research has studied their association or factors that increase resilience. The
      sample included 425 LGBs between the ages of 16 and 24 year. The majority had
      disclosed their sexual orientation to family or friends (98%) and 97% had someone
      in their lives who was accepting. Racial/ethnic minority and female participants
      in general reported lower levels of disclosure and acceptance. Most participants
      reported some form of sexual orientation-related victimization (94%).
      Victimization was associated with psychological distress, but a compensatory
      model indicated that in the context of this victimization both peer and family
      support had significant promotive effects. A test of a protective model found
      social support did not ameliorate negative effects of victimization. The positive
      effects of family support decreased with age. Peer and family support were
      particularly important, but they did not significantly dampen the negative
      effects of victimization. Our findings suggest that mental health professionals
      working with LGB youth should address social support and that public health
      approaches are needed to reduce levels of victimization.

PMID- 21731406
TI  - Sex drugs, peer connections, and HIV: Use and risk among African American,
      Latino, and Multiracial young men who have sex with men (YMSM) in Los Angeles and
      New York.
AB  - African American and Latino young men who have sex with men are at high risk for
      HIV infection. We administered brief intercept surveys (N=416) at 18 Black and
      Latino gay pride events in Los Angeles and New York in 2006 and 2007. Ordinal
      logistic regressions were used to model the effects of substance use during sex,
      peer connectedness, relationship status, and homelessness on condom use. Alcohol
      use, crystal use, homelessness, and having a primary relationship partner were
      negatively associated with condom use, while peer connectedness and marijuana use
      during sex were positively associated with condom use. Implications for service
      providers and future research are discussed.

PMID- 21731407
TI  - Ethnic Group Differences in the Outcomes of Multidisciplinary Pain Treatment.
AB  - OBJECTIVES: The aim of this prospective investigation was to evaluate ethnic
      group differences in pain-related outcomes following multidisciplinary chronic
      pain treatment. A prospective pre- and post-treatment assessment design was
      employed to investigate the effects of ethnicity on changes in pain-related
      variables following completion of a multidisciplinary pain treatment program.
      METHODS: One hundred fifty five chronic pain patients participating in a
      multidisciplinary pain treatment program completed measures of pain and mood both
      prior to and following the four-week treatment. Primary outcome variables
      included pain severity, pain-related interference, and depressive symptoms.
      RESULTS: Baseline differences between African-Americans and Whites were observed
      for depressive symptoms, but not for pain severity or pain-related interference.
      Following multidisciplinary pain treatment, both White and African-American
      patients displayed post-treatment reductions in depressive symptoms and pain
      related interference. However, White patients also reported reduced pain severity
      while African-Americans did not. CONCLUSIONS: The treatment approach used in the
      present study appeared to be less effective in reducing self-reported pain
      severity in African-American versus White patients, though both groups benefited
      in terms of reduced depressive symptoms and pain-related interference. Moreover,
      the observation that improvements in functioning occurred without reductions in
      pain severity in African-American patients suggests that differences may exist in
      treatment processes as a function of ethnic group, and will consequently be an
      important area for future research.

PMID- 21731408
TI  - Coping and Positive Affect in Adolescents of Mothers With and Without a History
      of Depression.
AB  - The adolescent children of depressed mothers are at increased risk for
      depression, but little is known about protective factors for these children.
      Maintenance of positive affect in a stressful context may be an important marker
      of resilience. Mothers with (n = 34) and without (n = 38) a history of depression
      and their adolescent children completed questionnaires regarding adolescents'
      coping and depressive symptoms and engaged in a 15 min videotaped interaction
      about family stress. Adolescents' observed behaviors were coded using the Iowa
      Family Interaction Rating Scales. No significant differences emerged in observed
      behavior between adolescents of mothers with and without a history of depression.
      Higher levels of primary and secondary control coping and lower levels of
      disengagement coping were related to higher levels of observed positive mood and
      fewer depressive symptoms in adolescents. Observed positive mood was related to
      fewer depressive symptoms in adolescents, even after accounting for maternal
      history of depression and current maternal depressive symptoms. Results suggest
      the importance of considering positive affect in the context of family stress as
      a marker of resilience in adolescents at risk for depression. The current study
      provides evidence for coping as a protective factor, related to higher levels of
      positive affect and fewer depressive symptoms, in adolescents exposed to maternal
      depressive symptoms.

PMID- 21731409
TI  - Promotion of Physical Activity Among Mexican-Origin Women in Texas and South
      Carolina: An Examination of Social, Cultural, Economic, and Environmental
      Factors.
AB  - Interventions to improve physical activity levels among Latinos must take into
      consideration the social, cultural, economic, and environmental contexts of
      Latino communities. We report findings of formative assessments related to
      Mexican-origin women's levels of readiness, willingness, and ability to
      participate in regular leisure time physical activity in two diverse locations,
      the Texas Lower Rio Grande Valley and the South Carolina Midlands. The ENLACE
      project employed a Community-Based Participatory Research approach. Formative
      assessment activities focused on identification of community assets and resources
      and exploration of community members' experiences, opinions, values, preferences,
      and perceived needs related to physical activity. Data sources included
      windshield tours, walkability assessments of local neighborhoods; community
      inventory exercises, focus groups, and individual interviews. Barriers to regular
      physical activity included the dominance of work and family responsibilities,
      social norms, lack of social support, social isolation, environmental
      constraints, economics, and low levels of personal knowledge and motivation.

PMID- 21731410
TI  - A Case of Premature Termination in a Treatment for Generalized Anxiety Disorder.
AB  - In this paper we present a case of failure in an integrative treatment for
      generalized anxiety disorder (GAD) combining cognitive-behavioral therapy, an
      empirically supported treatment for GAD, and interpersonal-emotional processing
      therapy. The client of focus dropped out of treatment after the eighth session.
      Based on our analysis of this case, we discuss the participant, technical and
      relationship factors that were likely implicated in this case of premature
      termination in both of the cognitive-behavioral and interpersonal-emotional
      processing segments that comprised the treatment. Implications for practice,
      training and future research are also discussed.

PMID- 21731411
TI  - Performance Trade-Off Analysis Comparing Different Front-End Configurations for a
      Digital X-ray Imager.
AB  - Performance of indirect digital x-ray imagers is typically limited by the front
      end components. Present x-ray-to-light converting phosphors significantly reduce
      detector resolution due to stochastic blurring and k-fluorescent x-ray
      reabsorption. Thinner phosphors improve resolution at the cost of lowering
      quantum detection efficiency (QDE) and increasing Swank noise. Magnifying fiber
      optic tapers (FOTs) are commonly used to increase the field-of-view of small
      sensor imagers, such as CMOS, CCD, or electron-multiplying CCD (EMCCD) based
      detectors, which results in a reduction in detector sensitivity and further
      reduces the MTF. We investigate performance trade-offs for different front-end
      configurations coupled to an EMCCD sensor with 8 MUm pixels. Six different
      columnar structured CsI(Tl) scintillators with thicknesses of 100, 200, 350, 500,
      and 1000 MUm type high-light (HL) and a 350 MUm type high-resolution (HR)
      (Hamamatsu) and four different FOTs with magnification ratios (M) of 1, 2.5, 3.3,
      and 4 were studied using the RQA5 x-ray spectrum. The relative signal of the
      different scintillators largely followed the relative QDE, indicating their light
      output per absorbed x-ray was similar, with the type HR CsI emitting 57% of the
      type HL. The efficiency of the FOTs was inversely proportional to M(2) with the M
      = 1 FOT transmitting 87% of the incident light. At 5 (10) cycles/mm, the CsI MTF
      was 0.38 (0.22), 0.33 (0.17), 0.37 (0.19), 0.23 (0.09), 0.19 (0.08), and 0.09
      (0.03) for the 100, 200, 350HR, 350, 500, and 1000 MUm CsI, respectively and the
      FOT MTF was 0.89 (0.84), 0.80 (0.72), 0.70 (0.60), and 0.69 (0.37) for M = 1,
      2.5, 3.3, and 4, respectively. The 1000, 500, and 350HR MUm CsI had the highest
      DQE for low, medium, and high spatial frequency ranges of 0 to 1.6, 1.6 to 4.5,
      and 4.5 to 10 cycles/mm, respectively. Larger FOT M resulted in a reduction in
      DQE. Quantifying performance of different front-end configurations will enable
      optimal selection of components for task-specific designs.

PMID- 21731412
TI  - Quantum Performance Analysis of an EMCCD-based X-ray Detector Using Photon
      Transfer Technique.
AB  - The low electronic noise, high resolution, and good temporal performance of
      electron-multiplying CCDs (EMCCDs) are ideally suited for applications
      traditionally served by x-ray image intensifiers. In order to improve an
      expandable clinical detector's field-of-view and have full control of the system
      performance, we have successfully built a solid-state x-ray detector. The photon
      transfer technique was used to quantify the EMCCD quantum performance in terms of
      sensitivity (or camera gain constant, K), read noise (RN), full-well capacity
      (FW), and dynamic range (DR). Measured results show the system maintains a K of
      11.3 +/- 0.9 e(-)/DN at unit gain, with a read noise of 71.5+/-6.0 e(-)rms at
      gain 1, which decreases proportionally with higher gains. The full well capacity
      was measured to be 31.3+/-2.7 ke(-), providing a dynamic range of 52.8+/-0.7 dB
      using the chip manufacturer specified clocking scheme. Similar performance was
      measured with other commercial camera systems. The manufacturer data sheet
      indicates a dynamic range of 66 dB is plausible with improved read noise and full
      well capacity. Different clocking schemes are under investigation to assess their
      impact on improving performance towards idealized values. EMCCD driver clock
      voltage levels were adjusted individually to check the influence on quantum
      performance. The clocks work to transfer charge from the image area to readout
      amplifier through the storage area, horizontal and multiplication registers.
      Results indicate that the clock that contributes to lateral overflow drain bias
      is essential to the system performance in terms of dynamic range and full well
      capacity. The serial register clocks used for transporting charge stored in the
      pixels of the memory lines to the output amplifier had the largest effect on RN,
      while others had less of an impact. Initial adjustment of these clocks resulted
      in a variability of 16% in the performance of dynamic range, 38% in read noise
      and 56% in full well capacity. Quantifying the quantum performance provides
      valuable insight into overall performance and enables optimal adjustment of the
      clocking scheme. Further improvements are expected.

PMID- 21731413
TI  - Willingness to treat drug dependence and depression: comparisons of future health
      professionals.
AB  - PURPOSE: Stigma-related feelings, including degree of enthusiasm and willingness
      to work with alcohol, drug, and mental disorder (ADM) patients, as well as
      anticipated success in such work, will be required for the United States to be
      successful in its new initiatives for ADM screening, brief intervention, and
      effective referral to treatment and rehabilitation services (SBIRT). This study
      investigates students of medicine and social work with respect to their stigma
      related feelings and degree of enthusiasm or willingness to treat patients
      affected by alcohol dependence, nicotine dependence, or major depression.
      Inference is strengthened by an anonymous online survey approach, with use of
      randomized reinforcers to gain at least partial experimental control of
      nonparticipation biases that otherwise are present in student survey data.
      MATERIAL AND METHODS: All students on required course rosters were asked to
      participate in a two-part in-class and online assessment; 222 participated, with
      a gradient of participation induced via randomly drawn reinforcers for online
      survey participation. Between-group comparisons were made with a multivariate
      generalized linear model and generalized estimating equations approach that
      adjusts for covariates. RESULTS: Medical and social work students did not differ
      from each other with respect to their willingness to treat patients affected by
      major depression, alcohol dependence, or nicotine dependence, but together were
      less willing to treat nicotine and alcohol dependence-affected patients as
      compared to depression-affected patients. Personal history was not associated
      with the students' willingness to treat, but men were less willing to treat.
      Drawing strength from the randomized reinforcer experimental design nested within
      this survey approach, the study evidence suggests potential nonparticipation bias
      in standard surveys on this topic. CONCLUSION: These results indicate that future
      health professionals may prefer to treat depression as opposed to drug dependence
      conditions. For SBIRT success, curriculum change with educational interventions
      may be needed to increase willingness to treat patients with neuropsychiatric
      conditions such as drug dependence. Future research requires attention to a
      possible problem of nonparticipation bias in surveys of this type.

PMID- 21731415
TI  - Above all, follow your dreams.

PMID- 21731414
TI  - Determining the benefits and objectives of a child health residency program for
      Canadian rural family physicians: An international qualitative research study.
AB  - OBJECTIVES: To clarify the need for an advanced child health training program for
      Canadian rural family physicians, and to determine the key learning objectives to
      enable graduates to become community leaders in child and youth health care.
      DESIGN: Qualitative educational research study. SETTING: Canada and Australia.
      METHODS: To gather data, the authors carried out semistructured interviews and
      focus groups with child care consultants, Canadian rural family physicians, child
      patients and parents, family medicine residents and Australian rural family
      physicians. Standards of qualitative methodology were applied to identify themes
      and subthemes. RESULTS: IT WAS DETERMINED THAT A FAMILY MEDICINE CHILD HEALTH
      PROGRAM WOULD PROVIDE THE FOLLOWING BENEFITS: enhanced care by family physicians,
      improved access to child care, increased attractiveness of family medicine as a
      career and reduced 'specialty burden'. FIVE KEY LEARNING OBJECTIVES FOR GRADUATES
      WERE IDENTIFIED: the ability to provide child-centred care, to care for acutely
      or critically ill children, to care for children with complex needs, to recognize
      and act on 'red flags', and to provide behavioural and mental health care. The
      Australian general practitioners confirmed that their training provided most of
      these benefits, and enabled them to achieve the objectives identified.
      CONCLUSION: The present study showed that multiple stakeholders believed that
      advanced training in child health for rural family physicians would provide
      better care for children. The study also identified key learning objectives for
      the program. The present research led to the establishment of a Family Medicine
      Child Health Residency Program
      (www.familymedicineuwo.ca/PostGrad/PGY3/ChildHealth.aspx) at The University of
      Western Ontario (London, Ontario).

PMID- 21731416
TI  - Iron deficiency is a public health problem in Canadian infants and children.

PMID- 21731417
TI  - Body mass index and the risk of acute injury in adolescents.
AB  - OBJECTIVE: To evaluate the relationship between body mass index (BMI) and acute
      injury in adolescents. METHODS: An analysis of cross-sectional data from the
      Canadian Community Health Survey (CCHS) Cycle 3.1 collected by Statistics Canada
      in 2005 was conducted. The CCHS is a population-based survey that collects
      information pertaining to the Canadian population health status, health care use
      and health determinants. The CCHS Cycle 3.1 included 132,221 respondents, of whom
      12,317 were 12 to 17 years of age. Multivariate logistic regression was used to
      estimate the odds of injury occurrence by BMI categories (obese, overweight and
      neither). RESULTS: The association between overweight and obese BMI levels and
      injury occurrence in the bivariate model was not significant after adjusting for
      sex, health status, activity levels and socioeconomic status (OR=1.10 [95% CI
      0.97 to 1.24] for overweight and OR=1.12 [95% CI 0.92 to 1.37] for obesity). A
      subanalysis of those with an injury in the past 12 months found an elevated odds
      of experiencing multiple injuries in the overweight group, after adjusting for
      age, health status and physical activity level (OR=1.43 [95% CI 1.16 to 1.77]).
      CONCLUSION: An increased risk of acute injury in obese and overweight adolescents
      was not observed. However, the subgroup analysis suggested that multiple injuries
      are relatively frequent in the overweight BMI group.

PMID- 21731418
TI  - Starting subcutaneous insulin doses in a paediatric population with newly
      diagnosed type 1 diabetes.
AB  - BACKGROUND: Starting subcutaneous insulin doses in children with newly diagnosed
      type 1 diabetes vary widely from 0.2 units/kg/day to 0.8 units/kg/day. AIM: To
      determine whether there are correlations between starting insulin dose and
      diabetes-related outcomes. METHODS: By reviewing the charts of children newly
      diagnosed with type 1 diabetes, the prevalence of hypoglycemia in the first 48 h
      was compared between those who received low (0.5 units/kg/day or less) and those
      who received high (greater than 0.5 units/kg/day) starting insulin doses.
      RESULTS: Forty-two children were initially prescribed a low dose of insulin, and
      55 children were given a high dose. Approximately one-third of children (36.4%)
      younger than six years of age who received a high starting dose of insulin had
      mild hypoglycemia within 48 h of subcutaneous insulin initiation, compared with
      16.0% of children six to 10 years of age and 5.3% of children older than 10 years
      of age. CONCLUSIONS: Hypoglycemia was not more frequent among children given high
      insulin starting doses. However, children younger than six years of age remained
      at increased risk for hypoglycemia.

PMID- 21731419
TI  - Emergency contraception.
AB  - Emergency contraception (EC) is an effective way to prevent an unintended or
      unplanned pregnancy. EC is available in two forms in Canada: a progestin-only
      method and a combined hormonal method, also known as the Yuzpe regimen. EC has
      been proven to be most effective within 72 h and up to 120 h after unprotected
      sexual intercourse. To date, the progestin-only method is the preferred method of
      EC recommended to teens because it is known for higher efficacy and fewer side
      effects, and is, therefore, more widely accepted over the combined method. Teens
      should also be counselled that the progestin-only method is widely available
      without a doctor's prescription across Canada.

PMID- 21731421
TI  - Management of HIV-exposed and HIV-infected children.

PMID- 21731420
TI  - Trans fats: What physicians should know.
AB  - Hydrogenation of fat products is used in the food industry to extend their shelf
      life. Trans fats are the result of partial hydrogenation of unsaturated fat.
      Trans fats increase low-density lipoprotein cholesterol and decrease high-density
      lipoprotein cholesterol, thus increasing the risk of cardiovascular disease.
      Canadians have one of the highest dietary intake of trans fat in the world.
      Health Canada has made recommendations to decrease the trans fat intake of
      Canadians. Physicians should be able to provide their patients with information
      on trans fats and their deleterious effects on health.

PMID- 21731422
TI  - ?
AB  - Le programme intitule " Etude des ecosystemes montagnards dans la region
      malgache" (RCP 225/CNRS; responsable: Recteur Renaud Paulian) avait pour ambition
      de degager leurs caracteres generaux, l'origine des elements constitutifs et de
      tester la validite d'un Domaine malgache des Hautes Montagnes propose par Humbert
      des 1951. De 1970 a 1973, trois campagnes (Andringitra; Chaines anosyennes et
      Ankaratra; Itremo, Ibity et Marojejy) ont permis une caracterisation ecologique
      des milieux particuliers ainsi que des analyses de systematique sur certains taxa
      connus pour leur interet biogeographique. La succession altitudinale des
      formations vegetales, definies par des criteres physionomiques et structuraux,
      est precisee par massif. Le dernier etage caracterise par le fourre ericoide et
      ses groupements associes ne correspond pas a l'Etage des Hautes Montagnes de
      l'Est africain. Des groupes de la faune (invertebres hexapodes: Collemboles et
      Dermapteres) indiquent une disjonction entre les massifs du Nord (Tsaratanana,
      Marojejy), ceux du Centre et du Sud; des elements de la flore (Pandanaceae,
      Araliaceae, Asteraceae) sont en cours d'analyse dans le meme sens. Le Domaine des
      Hautes montagnes a Madagascar est une realite ecologique mais ne peut etre defini
      floristiquement; chaque massif montagneux est une entite phytogeographique
      d'etages de vegetation interdependants inclus dans les differents Sous-Domaines
      du Centre. Les groupes peu mobiles de la faune indiquent globalement une
      dependance trophique et bioclimatique (effet tampon du climat intraforestier) vis
      a-vis des etages de vegetation, mais peuvent reagir a des microclimats locaux par
      des decalages a leurs limites.

PMID- 21731423
TI  - The GeoViz Toolkit: Using component-oriented coordination methods for geographic
      visualization and analysis.
AB  - In this paper we present the GeoViz Toolkit, an open-source, internet-delivered
      program for geographic visualization and analysis that features a diverse set of
      software components which can be flexibly combined by users who do not have
      programming expertise. The design and architecture of the GeoViz Toolkit allows
      us to address three key research challenges in geovisualization: allowing end
      users to create their own geovisualization and analysis component set on-the-fly,
      integrating geovisualization methods with spatial analysis methods, and making
      geovisualization applications sharable between users. Each of these tasks
      necessitates a robust yet flexible approach to inter-tool coordination. The
      coordination strategy we developed for the GeoViz Toolkit, called Introspective
      Observer Coordination, leverages and combines key advances in software
      engineering from the last decade: automatic introspection of objects, software
      design patterns, and reflective invocation of methods.

PMID- 21731424
TI  - A Semiparametric Bayesian Approach to Multivariate Longitudinal Data.
AB  - We extend the standard multivariate mixed model by incorporating a smooth time
      effect and relaxing distributional assumptions. We propose a semiparametric
      Bayesian approach to multivariate longitudinal data using a mixture of Polya
      trees prior distribution. Usually, the distribution of random effects in a
      longitudinal data model is assumed to be Gaussian. However, the normality
      assumption may be suspect, particularly if the estimated longitudinal trajectory
      parameters exhibit multimodality and skewness. In this paper we propose a mixture
      of Polya trees prior density to address the limitations of the parametric random
      effects distribution. We illustrate the methodology by analyzing data from a
      recent HIV-AIDS study.

PMID- 21731425
TI  - Collision Energetics in a Tandem Time-of-Flight (TOF/TOF) Mass Spectrometer with
      a Curved-Field Reflectron.
AB  - Collisions of fullerene ions (C(60) (+)) with helium and neon were carried out
      over a range of laboratory energies (3-20 keV) on a unique tandem time-of-flight
      (TOF/TOF) mass spectrometer equipped with a curved-field reflectron (CFR). The
      CFR enables focusing of product ions over a wide kinetic energy range. Thus, ions
      extracted from a laser desorption/ionization (LDI) source are not decelerated
      prior to collision, and collision energies in the laboratory frame are determined
      by the source extraction voltages. Comparison of product ion mass spectra
      obtained following collisions with inert gases show a time (and apparent mass)
      shift for product ions relative to those observed in spectra obtained by
      metastable dissociation (unimolecular decay), consistent with impulse collision
      models, in which interactions of helium with fullerene in the high energy range
      are primarily with a single carbon atom. In addition, within a narrow range of
      kinetic energies an additional peak corresponding to the capture of helium is
      observed for fragment ions C(50) (+), C(52) (+), C(54) (+), C(56) (+) and C(58)
      (+).

PMID- 21731426
TI  - Biologically Relevant Metal-Cation Binding Induces Conformational Changes in
      Heparin Oligosaccharides as Measured by Ion Mobility Mass Spectrometry.
AB  - Heparin interacts with many proteins and is involved in biological processes such
      as anticoagulation, angiogenesis, and antitumorigenic activities. These heparin
      protein interactions can be influenced by the binding of various metal ions to
      these complexes. In particular, physiologically relevant metal cations influence
      heparin-protein conformations through electronic interactions inherent to this
      polyanion. In this study, we employed ion mobility mass spectrometry (IMMS) to
      observe conformational changes that occur in fully-sulfated heparin
      octasaccharides after the successive addition of metal ions. Our results indicate
      that binding of positive counter ions causes a decrease in collision cross
      section (CCS) measurements, thus promoting a more compact octasaccharide
      structure.

PMID- 21731427
TI  - Simulation of Duty Cycle-Based Trapping and Ejection of Massive Ions Using Linear
      Digital Quadrupoles: the Enabling Technology for High Resolution Time-of-Flight
      Mass Spectrometry in the Ultra High Mass Range.
AB  - Duty cycle-based trapping and extraction processes have been investigated for
      linear digitally-driven multipoles by simulating ion trajectories. The duty
      cycles of the applied waveforms were adjusted so that an effective trapping or
      ejection electric field was created between the rods and the grounded end cap
      electrodes. By manipulating the duty cycles of the waveforms, the potentials of
      the multipole rods can be set equal for part of the waveform cycle. When all rods
      are negative for this period, the device traps positive ions and when all are
      positive, it ejects them in focused trajectories. Four Linac II electrodes[1]
      have been added between the quadrupole rods along the asymptotes to create an
      electric field along the symmetry axis for collecting the ions near the exit end
      cap electrode and prompt ejection. This method permits the ions to be collected
      and then ejected in a concentrated and collimated plug into the acceleration
      region of a time-of-flight mass spectrometer (TOFMS). Our method has been shown
      to be independent of mass. Because the resolution of orthogonal acceleration
      TOFMS depends primarily on the dispersion of the ions injected into the
      acceleration region and not on the ion mass, this technology will enable high
      resolution in the ultrahigh mass range (m/z > 20,000).

PMID- 21731428
TI  - Effects of new dietary fiber from Japanese Apricot (Prunus mume Sieb. et Zucc.)
      on gut function and intestinal microflora in adult mice.
AB  - Much attention has been focused recently on functional foods. Ume, the Japanese
      name for the apricot of Prunus mume Sieb. et Zucc., is an example of a Japanese
      traditional functional food. There are, however, few reports on the effects of
      fiber from this fruit on bowel function. With this objective, we prepared ume
      fiber to test the hypothesis that it can change gut function and intestinal flora
      in mice. Mice were fed an ume fiber (UF) or cellulose (CF) diet (control) for 40
      days. The fecal weight, fecal lipids, plasma lipids and cecal composition of the
      microflora were analyzed. The amount of feces was significantly greater in the UF
      group than in the CF group (p < 0.01). The fecal lipids content (% DW) of the
      feces sampled on the final day of the experiment were significantly greater in
      the UF group than in the CF group (p < 0.01). Plasma non-esterified fatty acids
      (NEFA) concentrations tended to be lower in the UF compared to the CF group (p =
      0.058). Occupation ratios of Bacteroides and Clostridium cluster IV were
      significantly greater in the cecal flora of the UF group. Our results suggest
      that ume fiber possesses the fecal lipid excretion effects and feces bulking
      effects.

PMID- 21731429
TI  - Physical properties of normal grade biodiesel and winter grade biodiesel.
AB  - In this study, optical and thermal properties of normal grade and winter grade
      palm oil biodiesel were investigated. Surface Plasmon Resonance and
      Photopyroelectric technique were used to evaluate the samples. The dispersion
      curve and thermal diffusivity were obtained. Consequently, the variation of
      refractive index, as a function of wavelength in normal grade biodiesel is faster
      than winter grade palm oil biodiesel, and the thermal diffusivity of winter grade
      biodiesel is higher than the thermal diffusivity of normal grade biodiesel. This
      is attributed to the higher palmitic acid C(16:0) content in normal grade than in
      winter grade palm oil biodiesel.

PMID- 21731430
TI  - Total phenolic contents and antioxidant capacities of herbal and tea infusions.
AB  - In order to supply new information on the antioxidant function of selected
      beverages for nutritionists and the general public, total phenolic contents of 51
      kinds of herbal and tea infusions made in China were measured by the Folin
      Ciocalteu method, and their antioxidant capacities were evaluated using ferric
      reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity
      (TEAC) assays. A significant correlation between FRAP and TEAC values suggested
      that antioxidant components in these beverages were capable of reducing oxidants
      and scavenging free radicals. The high correlation between antioxidant capacities
      and total phenolic contents indicated that phenolic compounds could be one of the
      main components responsible for antioxidant activities of these beverages.
      Generally, these beverages had high antioxidant capacities and total phenolic
      contents, and could be important dietary sources of antioxidant phenolics for
      prevention of diseases caused by oxidative stress.

PMID- 21731431
TI  - Calpain activator dibucaine induces platelet apoptosis.
AB  - Calcium-dependent calpains are a family of cysteine proteases that have been
      demonstrated to play key roles in both platelet glycoprotein Ibalpha shedding and
      platelet activation and altered calpain activity is associated with thrombotic
      thrombocytopenic purpura. Calpain activators induce apoptosis in several types of
      nucleated cells. However, it is not clear whether calpain activators induce
      platelet apoptosis. Here we show that the calpain activator dibucaine induced
      several platelet apoptotic events including depolarization of the mitochondrial
      inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of
      Bcl-2 and Bcl-X(L), caspase-3 activation and phosphatidylserine exposure.
      Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum
      metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce
      platelet activation as detected by P-selectin expression and PAC-1 binding.
      However, platelet aggregation induced by ristocetin or alpha-thrombin, platelet
      adhesion and spreading on von Willebrand factor were significantly inhibited in
      platelets treated with dibucaine. Taken together, these data indicate that
      dibucaine induces platelet apoptosis and platelet dysfunction.

PMID- 21731432
TI  - Geometrical conditions indispensable for muscle contraction.
AB  - Computer simulation has uncovered the geometrical conditions under which the
      vertebrate striated muscle sarcomere can contract. First, all thick filaments
      should have identical structure, namely: three myosin cross-bridges, building a
      crown, should be aligned at angles of 0 degrees , 120 degrees , 180 degrees , and
      the successive crowns and the two filament halves should be turned around 120
      degrees . Second, all thick filaments should act simultaneously. Third,
      coordination in action of the myosin cross-bridges should exist, namely: the
      three cross-bridges of a crown should act simultaneously and the cross-bridge
      crowns axially 43 and 14.333 nm apart should act, respectively, simultaneously
      and with a phase shift. Fifth, six thin filaments surrounding the thick filament
      should be turned around 180 degrees  to each other in each sarcomere half. Sixth,
      thin filaments should be oppositely oriented in relation to the sarcomere middle.
      Finally, the structure of each of the thin filaments should change in consequence
      of strong interaction with myosin heads, namely: the axial distance and the
      angular alignment between neighboring actin monomers should be, respectively,
      2.867 nm and 168 degrees  instead of 2.75 nm and 166.15 degrees . These
      conditions ensure the stereo-specific interaction between actin and myosin and
      good agreement with the data gathered by electron microscopy and X-ray
      diffraction methods. The results suggest that the force is generated not only by
      the myosin cross-bridges but also by the thin filaments; the former acts by
      cyclical unwrapping and wrapping the thick filament backbone, and the latter
      byelongation.

PMID- 21731433
TI  - Release of bacteriocins from nanofibers prepared with combinations of poly(d,l
      lactide) (PDLLA) and poly(ethylene oxide) (PEO).
AB  - Plantaricin 423, produced by Lactobacillus plantarum, and bacteriocin ST4SA
      produced by Enterococcus mundtii, were electrospun into nanofibers prepared from
      different combinations of poly(d,l-lactide) (PDLLA) and poly(ethylene oxide)
      (PEO) dissolved in N,N-dimethylformamide (DMF). Both peptides were released from
      the nanofibers with a high initial burst and retained 88% of their original
      antimicrobial activity at 37  degrees C. Nanofibers have the potential to serve
      as carrier matrix for bacteriocins and open a new field in developing controlled
      antimicrobial delivery systems for various applications.

PMID- 21731434
TI  - Fiber concentrate from orange (Citrus sinensis L.) bagase: characterization and
      application as bakery product ingredient.
AB  - Orange is a tropical fruit used in the juice industry, yielding important
      quantities of by products. The objective of this work was to obtain a dietary
      fiber-rich orange bagasse product (DFROBP), evaluate its chemical composition and
      its use in the preparation of a bakery product (muffin). Muffins containing two
      different levels of DFROBP were studied regarding chemical composition, in vitro
      starch digestibility, predicted glyceamic index and acceptability in a sensory
      test. DFROBP showed low fat and high dietary fiber contents. The soluble and
      insoluble dietary fiber fractions were balanced, which is of importance for the
      health beneficial effects of fiber sources. DFROBP-containing muffins showed the
      same rapidly digestible starch content as the reference muffin, whilst the slowly
      digestible starch level increased with the addition of DFROBP. However, the
      resistant starch content decreased when DFROBP increased in the muffin. The
      addition of DFROBP to muffin decreased the predicted glyceamic index, but no
      difference was found between the muffins prepared with the two DFROBP levels. The
      sensory score did not show difference between control muffin and that added with
      10% of DFROBP. The addition of DFROBP to bakery products can be an alternative
      for people requiring low glyceamic response.

PMID- 21731435
TI  - Fabrication and intermolecular interactions of silk fibroin/hydroxybutyl chitosan
      blended nanofibers.
AB  - The native extracellular matrix (ECM) is composed of a cross-linked porous
      network of multifibril collagens and glycosaminoglycans. Nanofibrous scaffolds of
      silk fibroin (SF) and hydroxybutyl chitosan (HBC) blends were fabricated using
      1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and trifluoroacetic acid (TFA) as
      solvents to biomimic the native ECM via electrospinning. Scanning electronic
      microscope (SEM) showed that relatively uniform nanofibers could be obtained when
      12% SF was blended with 6% HBC at the weight ratio of 50:50. Meanwhile, the
      average nanofibrous diameter increased when the content of HBC in SF/HBC blends
      was raised from 20% to 100%. Fourier transform infrared spectra (FTIR) and (13)C
      nuclear magnetic resonance (NMR) showed SF and HBC molecules existed in hydrogen
      bonding interactions but HBC did not induce conformation of SF transforming from
      random coil form to beta-sheet structure. X-ray diffraction (XRD) confirmed the
      different structure of SF/HBC blended nanofibers from both SF and HBC.
      Thermogravimetry-Differential thermogravimetry (TG-DTG) results demonstrated that
      the thermal stability of SF/HBC blend nanofibrous scaffolds was improved. The
      results indicated that the rearrangement of HBC and SF molecular chain formed a
      new structure due to stronger hydrogen bonding between SF and HBC. These
      electrospun SF/HBC blended nanofibers may provide an ideal tissue engineering
      scaffold and wound dressing.

PMID- 21731436
TI  - Characterization of doped amorphous silicon thin films through the investigation
      of dopant elements by glow discharge spectrometry: a correlation of conductivity
      and bandgap energy measurements.
AB  - The determination of optical parameters, such as absorption and extinction
      coefficients, refractive index and the bandgap energy, is crucial to understand
      the behavior and final efficiency of thin film solar cells based on hydrogenated
      amorphous silicon (a-Si:H). The influence of small variations of the gas flow
      rates used for the preparation of the p-a-SiC:H layer on the bandgap energy, as
      well as on the dopant elements concentration, thickness and conductivity of the p
      layer, is investigated in this work using several complementary techniques. UV
      NIR spectrophotometry and ellipsometry were used for the determination of bandgap
      energies of four p-a-SiC:H thin films, prepared by using different B(2)H(6) and
      SiH(4) fluxes (B(2)H(6) from 12 sccm to 20 sccm and SiH(4) from 6 sccm to 10
      sccm). Moreover, radiofrequency glow discharge optical emission spectrometry
      technique was used for depth profiling characterization of p-a-SiC:H thin films
      and valuable information about dopant elements concentration and distribution
      throughout the coating was found. Finally, a direct relationship between the
      conductivity of p-a-SiC:H thin films and the dopant elements concentration,
      particularly boron and carbon, was observed for the four selected samples.

PMID- 21731437
TI  - Highly unsaturated binuclear butadiene iron carbonyls: quintet spin states,
      perpendicular structures, agostic hydrogen atoms, and iron-iron multiple bonds.
AB  - The highly unsaturated binuclear butadiene iron carbonyls
      (C(4)H(6))(2)Fe(2)(CO)(n) (n = 2, 1) have been examined using density functional
      theory. For (C(4)H(6))(2)Fe(2)(CO)(n) (n = 2, 1), both coaxial and perpendicular
      structures are found. The global minima of (C(4)H(6))(2)Fe(2)(CO)(n) (n = 2, 1)
      are the perpendicular structures 2Q-1 and 1Q-1, respectively, with 17- and 15
      electron configurations for the iron atoms leading to quintet spin states. The
      Fe=Fe distance of 2.361 A (M06-L) in the (C(4)H(6))(2)Fe(2)(CO)(2) structure 2Q-1
      suggests a formal double bond. The Fe=Fe bond distance in the
      (C(4)H(6))(2)Fe(2)(CO) structure 1Q-1 is even shorter at 2.273 A (M06-L),
      suggesting a triple bond. Higher energy (C(4)H(6))(2)Fe(2)(CO)(n) (n = 2, 1)
      structures include structures in which a bridging butadiene ligand is bonded to
      one of the iron atoms as a tetrahapto ligand and to the other iron atom through
      two agostic hydrogen atoms from the end CH(2) groups. Singlet
      (C(4)H(6))(2)Fe(2)(CO) structures with formal Fe-Fe quadruple bonds of lengths
      ~2.05 A were also found but at very high energies (~47 kcal/mol) relative to the
      global minimum.

PMID- 21731438
TI  - One-dimensional hydrogen-bonded infinite chain from nickel(II) tetraaza
      macrocyclic complex and 1,2-cyclopentanedicarboxylate ligand.
AB  - The reaction of [Ni(L)]Cl(2).2H(2)O (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo
      [14,4,0(1.18),0(7.12)]docosane) with trans-1,2-cyclopentanedicarboxylic acid
      (H(2)-cpdc) yields a 1D hydrogen-bonded infinite chain with formula [Ni(L)(H
      cpdc(-))(2)] (1). This complex has been characterized by X-ray crystallography,
      spectroscopy and cyclic voltammetry. The crystal structure of 1 exhibits a
      distorted octahedral geometry about Ni atom with four nitrogen atoms of the
      macrocycle and two oxygen atoms of the H-cpdc(-) ligand at the axial position.
      Compound 1 crystallizes in the monoclinic system P2(1)/c with a = 8.7429(17), b =
      10.488(2), c = 18.929(4) A, beta = 91.82(2), V = 1734.8(6) A(3), Z = 2.
      Electronic spectrum of 1 reveals a high-spin octahedral environment. Cyclic
      voltammetry of 1 undergoes two waves of a one-electron transfer corresponding to
      Ni(II)/Ni(III) and Ni(II)/Ni(I) processes.

PMID- 21731439
TI  - Improving the accuracy of Density Functional Theory (DFT) calculation for
      homolysis bond dissociation energies of Y-NO bond: generalized regression neural
      network based on grey relational analysis and principal component analysis.
AB  - We propose a generalized regression neural network (GRNN) approach based on grey
      relational analysis (GRA) and principal component analysis (PCA) (GP-GRNN) to
      improve the accuracy of density functional theory (DFT) calculation for homolysis
      bond dissociation energies (BDE) of Y-NO bond. As a demonstration, this combined
      quantum chemistry calculation with the GP-GRNN approach has been applied to
      evaluate the homolysis BDE of 92 Y-NO organic molecules. The results show that
      the ull-descriptor GRNN without GRA and PCA (F-GRNN) and with GRA (G-GRNN)
      approaches reduce the root-mean-square (RMS) of the calculated homolysis BDE of
      92 organic molecules from 5.31 to 0.49 and 0.39 kcal mol(-1) for the B3LYP/6-31G
      (d) calculation. Then the newly developed GP-GRNN approach further reduces the
      RMS to 0.31 kcal mol(-1). Thus, the GP-GRNN correction on top of B3LYP/6-31G (d)
      can improve the accuracy of calculating the homolysis BDE in quantum chemistry
      and can predict homolysis BDE which cannot be obtained experimentally.

PMID- 21731440
TI  - Multi-step usage of in vivo models during rational drug design and discovery.
AB  - In this article we propose a systematic development method for rational drug
      design while reviewing paradigms in industry, emerging techniques and
      technologies in the field. Although the process of drug development today has
      been accelerated by emergence of computational methodologies, it is a herculean
      challenge requiring exorbitant resources; and often fails to yield clinically
      viable results. The current paradigm of target based drug design is often
      misguided and tends to yield compounds that have poor absorption, distribution,
      metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo
      organism based approach allowing for a multidisciplinary inquiry into potent and
      selective molecules is an excellent place to begin rational drug design. We will
      review how organisms like the zebrafish and Caenorhabditis elegans can not only
      be starting points, but can be used at various steps of the drug development
      process from target identification to pre-clinical trial models. This systems
      biology based approach paired with the power of computational biology; genetics
      and developmental biology provide a methodological framework to avoid the
      pitfalls of traditional target based drug design.

PMID- 21731441
TI  - Glass formation, chemical properties and surface analysis of Cu-based bulk
      metallic glasses.
AB  - This paper reviews the influence of alloying elements Mo, Nb, Ta and Ni on glass
      formation and corrosion resistance of Cu-based bulk metallic glasses (BMGs). In
      order to obtain basic knowledge for application to the industry, corrosion
      resistance of the Cu-Hf-Ti-(Mo, Nb, Ta, Ni) and Cu-Zr-Ag-Al-(Nb) bulk glassy
      alloy systems in various solutions are reported in this work. Moreover, X-ray
      photoelectron spectroscopy (XPS) analysis is performed to clarify the surface
      related chemical characteristics of the alloy before and after immersion in the
      solutions; this has lead to a better understanding of the correlation between the
      surface composition and the corrosion resistance.

PMID- 21731442
TI  - Characterization of a deswapped triple mutant bovine odorant binding protein.
AB  - The stability and functionality of GCC-bOBP, a monomeric triple mutant of bovine
      odorant binding protein, was investigated, in the presence of denaturant and in
      acidic pH conditions, by both protein and 1-aminoanthracene ligand fluorescence
      measurements, and compared to that of both bovine and porcine wild type
      homologues. Complete reversibility of unfolding was observed, though refolding
      was characterized by hysteresis. Molecular dynamics simulations, performed to
      detect possible structural changes of the monomeric scaffold related to the
      presence of the ligand, pointed out the stability of the beta-barrel lipocalin
      scaffold.

PMID- 21731443
TI  - Molecular recognition of arginine by supramolecular complexation with calixarene
      crown ether based on surface plasmon resonance.
AB  - Arginine plays an important role in cell division and the functioning of the
      immune system. We describe a novel method by which arginine can be identified
      using an artificial monolayer based on surface plasmon resonance (SPR). The
      affinity of arginine binding its recognition molecular was compared to that of
      lysine. In fabrication of an arginine sensing interface, a calix[4]crown ether
      monolayer was anchored onto a gold surface and then characterized by Fourier
      Transform infrared reflection absorption spectroscopy, atomic force microscopy,
      and cyclic voltammetry. The interaction between arginine and its host compound
      was investigated by SPR. The calix[4]crown ether was found to assemble as a
      monolayer on the gold surface. Recognition of calix[4]crown monolayer was
      assessed by the selective binding of arginine. Modification of the SPR chip with
      the calix[4]crown monolayer provides a reliable and simple experimental platform
      for investigation of arginine under aqueous conditions.

PMID- 21731444
TI  - Dextran sulfate sodium inhibits alanine synthesis in Caco-2 cells.
AB  - To understand and characterize the pathogenic mechanisms of inflammatory bowel
      disease, dextran sulfate sodium (DSS) has been used to induce acute and chronic
      colitis in animal models by causing intestinal epithelium damage. The mechanism
      of action of DSS in producing this outcome is not well understood. In an effort
      to understand how DSS might impact epithelial cell metabolism, we studied the
      intestinal epithelial cell line Caco-2 incubated with 1% DSS over 56 hours using
      (1)H NMR spectroscopy. We observed no difference in cell viability as compared to
      control cultures, and an approximately 1.5-fold increase in IL-6 production upon
      incubation with 1% DSS. The effect on Caco-2 cell metabolism as measured through
      changes in the concentration of metabolites in the cell supernatant included a
      three-fold decrease in the concentration of alanine. Given that the
      concentrations of other amino acids in the cell culture supernatant were not
      different between treated and control cultures over 56 hours suggest that DSS
      inhibits alanine synthesis, specifically alanine aminotransferase, without
      affecting other key metabolic pathways. The importance of alanine
      aminotransferase in inflammatory bowel disease is discussed.

PMID- 21731445
TI  - Lead, cadmium and cobalt (Pb, Cd, and Co) leaching of glass-clay containers by pH
      effect of food.
AB  - Recent studies have shown that handcrafted glass-clay containers are a health
      risk because they can be contaminated by heavy metals, which can be transferred
      to food, thus reaching the human body to potentially cause illness. Therefore, in
      the present work, we evaluate the leaching of lead, cadmium, and cobalt from
      glass-clay containers into two types of food: tomato sauce (salsa), and chickpea
      puree. The containers were obtained from four regions in the Mexican state of
      Hidalgo. Repetitive extractions from the containers were carried out to quantify
      the leaching of the heavy metals into the salsa, the chickpea puree, and acetic
      acid using the technique proposed by the USFDA. The results show that greater use
      of the containers leads to more leaching of heavy metals into both types of food
      and into the acetic acid, with the greatest metal extraction recorded for the
      Ixmiquilpan vessels. These results indicate that the metals present in the glass
      clay containers leach into the food and that increased reuse increases the risk
      to the people who use them in food preparation.

PMID- 21731446
TI  - Individual variations in inorganic arsenic metabolism associated with AS3MT
      genetic polymorphisms.
AB  - Individual variations in inorganic arsenic metabolism may influence the toxic
      effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze
      the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent
      arsenical, may play a role in arsenic metabolism in humans. Since the genetic
      polymorphisms of AS3MT gene may be associated with the susceptibility to
      inorganic arsenic toxicity, relationships of several single nucleotide
      polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been
      investigated. Here, we summarize our recent findings and other previous studies
      on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans.
      Results of genotype dependent differences in arsenic metabolism for most of SNPs
      in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT
      12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic
      methylation regardless of the populations examined for the analysis. Thus, these
      SNPs may be useful indicators to predict the arsenic metabolism via methylation
      pathways.

PMID- 21731447
TI  - Effect of 2-hydroxypropyl-beta-cyclodextrin on solubility of sparingly soluble
      drug derivatives of anthranilic acid.
AB  - Guest-host complex formation of three drug derivatives of anthranilic acid,
      mefenamic acid, niflumic acid, and flufenamic acid with 2-hydroxypropyl-beta
      cyclodextrin (2HP-beta-CD) in aqueous solutions was investigated using "Phase
      solubility study" with UV-vis spectrophotometry. Solubility of sparingly soluble
      drugs has been improved by addition of 2HP-beta-CD at two temperatures 298.15 K
      and 310.15 K and two pH values 2 and 7. The influence of different 2HP-beta-CD
      concentration on solubility of drugs at different pH and temperatures has been
      investigated. The 2HP-beta-CD-drug complex stability constants (K(s)), and
      dissociations constants (K(d)), as well as the thermodynamic parameters of
      reaction, i.e., the free energy change (DeltaG), the enthalpy change (DeltaH) and
      the entropy change (DeltaS), were determined. The experimental data indicated
      formation of 1:1 inclusion complexes, which were found effective binders
      increasing the solubility of drugs.

PMID- 21731448
TI  - Optimization of antibacterial activity of Perilla frutescens var. acuta leaf
      against Staphylococcus aureus using evolutionary operation factorial design
      technique.
AB  - This study was undertaken to optimize extraction using evolutionary operation
      factorial (EVOP) design technique to elicit the antibacterial activity of Perilla
      frutescens var. acuta leaf against Staphylococcus aureus ATCC6538. Higher
      antibacterial activity was achieved at higher extraction temperature and over a
      longer extraction time. Antibacterial activity was not affected by
      differentiation of the ethanol concentration in the extraction solvent. The
      maximum antibacterial activity of ethanolic extract of P. frutescens leaf against
      S. aureus was obtained at 75  degrees C (R = -0.7904(**)) extraction temperature,
      24 h (R = -0.7273(**)) extraction time, and 45% (R = -0.0635) ethanol
      concentration. The population of S. aureus was decreased from 7.535 log CFU/mL in
      the initial set to 4.865 log CFU/mL in the third set by EVOP factorial design
      technique, as well as to 2.600 log CFU/mL by extraction with ethyl acetate.
      Further, the ethyl acetate extract revealed the highest phenolic contents (111.3
      +/- 8.6 mg% of dry sample) as compared to the other extracts. Also, the scanning
      electronic microscopic study of the ethanolic extract of P. frutescens revealed
      potential detrimental effect on the morphology of S. aureus.

PMID- 21731450
TI  - Reactive oxygen species released from hypoxic hepatocytes regulates MMP-2
      expression in hepatic stellate cells.
AB  - Hypoxia is a common environmental stress factor and is associated with
      fibrogenesis. Matrix metalloproteinase-2 (MMP-2), produced by hepatic stellate
      cells (HSCs), plays an important role in liver fibrogenesis. However,
      inconsistent results have been reported on the impact of hypoxia on MMP-2
      expression and activity in HSCs. We speculated that cell-cell interaction is
      involved in the regulation of MMP-2 expression and activity at low oxygen level
      in vivo. Therefore, in this report we investigated the mechanism by which hypoxic
      hepatocytes regulates MMP-2 expression in HSCs. Our results showed that the
      conditioned medium from hypoxia-treated rat hepatocytes strongly induced the
      expression of MMP-2 mRNA and protein in rat HSC-T6 cells. Reduced glutathione
      neutralized ROS released from hypoxic hepatocytes, leading to reduced MMP-2
      expression in HSC-T6 cells. In addition, phospho-IkappaB-alpha protein level was
      increased in HSC-T6 cells treated with hypoxia conditioned medium, and NF-kappaB
      signaling inhibitor inhibited MMP-2 expression in HSC-T6 cells. Taken together,
      our data suggest that ROS is an important factor released by hypoxic hepatocytes
      to regulate MMP-2 expression in HSCs, and NF-kappaB signaling is crucially
      involved in ROS-induced MMP-2 expression in HSCs. Our findings suggest that
      strategies aimed at antagonizing the generation of ROS in hypoxic hepatocytes and
      inhibiting NF-kappaB signaling in HSCs may represent novel therapeutic options
      for liver fibrosis.

PMID- 21731449
TI  - Nutritional deficiencies and phospholipid metabolism.
AB  - Phospholipids are important components of the cell membranes of all living
      species. They contribute to the physicochemical properties of the membrane and
      thus influence the conformation and function of membrane-bound proteins, such as
      receptors, ion channels, and transporters and also influence cell function by
      serving as precursors for prostaglandins and other signaling molecules and
      modulating gene expression through the transcription activation. The components
      of the diet are determinant for cell functionality. In this review, the effects
      of macro and micronutrients deficiency on the quality, quantity and metabolism of
      different phospholipids and their distribution in cells of different organs is
      presented. Alterations in the amount of both saturated and polyunsaturated fatty
      acids, vitamins A, E and folate, and other micronutrients, such as zinc and
      magnesium, are discussed. In all cases we observe alterations in the pattern of
      phospholipids, the more affected ones being phosphatidylcholine,
      phosphatidylethanolamine and sphingomyelin. The deficiency of certain nutrients,
      such as essential fatty acids, fat-soluble vitamins and some metals may
      contribute to a variety of diseases that can be irreversible even after
      replacement with normal amount of the nutrients. Usually, the sequelae are more
      important when the deficiency is present at an early age.

PMID- 21731451
TI  - A Quantitative Structure-Property Relationship (QSPR) Study of aliphatic alcohols
      by the method of dividing the molecular structure into substructure.
AB  - A quantitative structure-property relationship (QSPR) analysis of aliphatic
      alcohols is presented. Four physicochemical properties were studied: boiling
      point (BP), n-octanol-water partition coefficient (lg P(OW)), water solubility
      (lg W) and the chromatographic retention indices (RI) on different polar
      stationary phases. In order to investigate the quantitative structure-property
      relationship of aliphatic alcohols, the molecular structure ROH is divided into
      two parts, R and OH to generate structural parameter. It was proposed that the
      property is affected by three main factors for aliphatic alcohols, alkyl group R,
      substituted group OH, and interaction between R and OH. On the basis of the
      polarizability effect index (PEI), previously developed by Cao, the novel
      molecular polarizability effect index (MPEI) combined with odd-even index (OEI),
      the sum eigenvalues of bond-connecting matrix (SX(1CH)) previously developed in
      our team, were used to predict the property of aliphatic alcohols. The sets of
      molecular descriptors were derived directly from the structure of the compounds
      based on graph theory. QSPR models were generated using only calculated
      descriptors and multiple linear regression techniques. These QSPR models showed
      high values of multiple correlation coefficient (R > 0.99) and Fisher-ratio
      statistics. The leave-one-out cross-validation demonstrated the final models to
      be statistically significant and reliable.

PMID- 21731452
TI  - Economic optimized medium for tensio-active agent production by Candida sphaerica
      UCP0995 and application in the removal of hydrophobic contaminant from sand.
AB  - Statistical experimental designs and response surface methodology were employed
      to optimize the concentrations of agroindustrial residues as soybean oil (SORR)
      from refinery, and corn steep liquor (CSL) from corn industry, for tensio-active
      agent produced by Candida sphaerica UCP 0995. Three 2(2) full factorial design
      were applied sequentially to investigate the effects of the concentrations and
      interactions of soybean oil refinery residue and corn steep liquor on the surface
      tension of free-cell culture broth for 144 h. Two 2(2) central composite designs
      and response surface methodology were adopted to derive a statistical model to
      measure the effect of SORR and CSL on the surface tension of the free-cell
      culture broth for 144 h. The regression equation obtained from the experimental
      data using a central composite design was solved, and by analyzing the response
      surface contour plots, the optimal concentrations of the constituents of the
      medium were determined: 8.63% v/v (?9% v/v) of SORR and 8.80% v/v (?9% v/v) CSL.
      The minimum surface tension predicted and experimentally confirmed was 25.25
      mN/m. The new biosurfactant, denominated Lunasan, recovered 95% of motor oil
      adsorbed in a sand sample, thus showing great potential for use in bioremediation
      processes, especially in the petroleum industry.

PMID- 21731453
TI  - YueF overexpression inhibits cell proliferation partly through p21 upregulation
      in renal cell carcinoma.
AB  - YueF is a novel putative tumor suppressor gene that can inhibit proliferation and
      induce apoptosis in hepatoma cells, but its role in renal cell carcinoma (RCC)
      remains unclear. Here, we examined the expression of the YueF gene in RCC tissues
      and the effect of YueF on cell proliferation in RCC 786-0 cells. The results
      showed that YueF was expressed at high levels in normal kidney tissues and cell
      lines but was reduced or absent in RCC tissues and 786-0 cells. Lentivirus
      mediated YueF overexpression in RCC 786-0 cells caused cell-cycle arrest in the
      G1 phase and dramatically reduced proliferation in culture. YueF overexpression
      resulted in increased protein levels of p53 and p21(WAF1/Cip1), whereas the
      protein levels of cyclin D1 and pRb were decreased. The proliferation defects
      caused by YueF overexpression could be partially rescued by the expression of p21
      siRNA. These findings suggest a critical role for p21 in the YueF-induced growth
      inhibition of 786-0 cells and provide novel insights into the mechanism
      underlying the tumor-suppressive action of YueF.

PMID- 21731454
TI  - Enhancement of salinity tolerance during rice seed germination by presoaking with
      hemoglobin.
AB  - Salinity stress is an important environmental constraint limiting the
      productivity of many crops worldwide. In this report, experiments were conducted
      to investigate the effects of seed presoaking by bovine hemoglobin, an inducer of
      heme oxygenase-1 (HO-1), on salinity tolerance in rice (Oryza sativa) plants. The
      results showed that different concentrations of the hemoglobin (0.01, 0.05, 0.2,
      1.0, and 5.0 g/L) differentially alleviated the inhibition of rice seed
      germination and thereafter seedling shoot growth caused by 100 mM NaCl stress,
      and the responses of 1.0 g/L hemoglobin was the most obvious. Further analyses
      showed that application of hemoglobin not only increased the HO-1 gene
      expression, but also differentially induced catalase (CAT), ascorbate peroxidase
      (APX), and superoxide dismutase (SOD) activities or transcripts, thus decreasing
      the lipid peroxidation in germinating rice seeds subjected to salt stress.
      Compared with non-hemoglobin treatment, hemoglobin presoaking also increased the
      potassium (K) to sodium (Na) ratio both in the root and shoot parts after
      salinity stress. The effect is specific for HO-1 since the potent HO-1 inhibitor
      zinc protoporphyrin IX (ZnPPIX) blocked the positive actions of hemoglobin on
      seed germination and seedling shoot growth. Overall, these results suggested that
      hemoglobin performs an advantageous role in enhancement of salinity tolerance
      during rice seed germination.

PMID- 21731455
TI  - Global transcriptomic profiling using small volumes of whole blood: a cost
      effective method for translational genomic biomarker identification in small
      animals.
AB  - Blood is an ideal tissue for the identification of novel genomic biomarkers for
      toxicity or efficacy. However, using blood for transcriptomic profiling presents
      significant technical challenges due to the transcriptomic changes induced by ex
      vivo handling and the interference of highly abundant globin mRNA. Most whole
      blood RNA stabilization and isolation methods also require significant volumes of
      blood, limiting their effective use in small animal species, such as rodents. To
      overcome these challenges, a QIAzol-based RNA stabilization and isolation method
      (QSI) was developed to isolate sufficient amounts of high quality total RNA from
      25 to 500 MUL of rat whole blood. The method was compared to the standard PAXgene
      Blood RNA System using blood collected from rats exposed to saline or
      lipopolysaccharide (LPS). The QSI method yielded an average of 54 ng total RNA
      per MUL of rat whole blood with an average RNA Integrity Number (RIN) of 9, a
      performance comparable with the standard PAXgene method. Total RNA samples were
      further processed using the NuGEN Ovation Whole Blood Solution system and cDNA
      was hybridized to Affymetrix Rat Genome 230 2.0 Arrays. The microarray QC
      parameters using RNA isolated with the QSI method were within the acceptable
      range for microarray analysis. The transcriptomic profiles were highly correlated
      with those using RNA isolated with the PAXgene method and were consistent with
      expected LPS-induced inflammatory responses. The present study demonstrated that
      the QSI method coupled with NuGEN Ovation Whole Blood Solution system is cost
      effective and particularly suitable for transcriptomic profiling of minimal
      volumes of whole blood, typical of those obtained with small animal species.

PMID- 21731456
TI  - Functioning nanomachines seen in real-time in living bacteria using single
      molecule and super-resolution fluorescence imaging.
AB  - Molecular machines are examples of "pre-established" nanotechnology, driving the
      basic biochemistry of living cells. They encompass an enormous range of function,
      including fuel generation for chemical processes, transport of molecular
      components within the cell, cellular mobility, signal transduction and the
      replication of the genetic code, amongst many others. Much of our understanding
      of such nanometer length scale machines has come from in vitro studies performed
      in isolated, artificial conditions. Researchers are now tackling the challenges
      of studying nanomachines in their native environments. In this review, we outline
      recent in vivo investigations on nanomachines in model bacterial systems using
      state-of-the-art genetics technology combined with cutting-edge single-molecule
      and super-resolution fluorescence microscopy. We conclude that single-molecule
      and super-resolution fluorescence imaging provide powerful tools for the
      biochemical, structural and functional characterization of biological
      nanomachines. The integrative spatial, temporal, and single-molecule data
      obtained simultaneously from fluorescence imaging open an avenue for systems
      level single-molecule cellular biophysics and in vivo biochemistry.

PMID- 21731457
TI  - An oligodeoxynucleotide with promising modulation activity for the proliferation
      and activation of osteoblast.
AB  - The paper explored the regulatory role of oligodeoxynucleotides (ODNs) with
      specific sequences in the proliferation and activation of osteoblast, using human
      osteoblast-like cell line MG 63 as the model. Through the administration of ODNs
      to MG 63 cells at a concentration of 1.0 MUg/mL, ODN MT01 with positive effects
      on proliferation and activation of osteoblast was selected from 11 different ODNs
      by methyl thiazolyl tetrazolium (MTT) assay and alkaline phosphatase (ALP)
      activity measurement. To get a deeper insight into the molecular mechanism,
      effects of ODN MT01 treatment on the expression level of Sp7, runx-2, collagen-I,
      osteoprotegerin (OPG) and RANK ligand (RANKL) were determined using quantitative
      real time PCR and Western blotting. Remarkably, the mRNA and protein expression
      levels of Sp7, runx-2, collagen-I and OPG were improved after ODN MT01 treatment.
      Meanwhile, the protein expression level of RANKL was dramatically decreased.
      These results suggested that ODN MT01 had a significant impact in facilitating
      osteogenic proliferation and activation, and provided a direct evidence for the
      notion that single strand ODN could regulate the balance of bone formation and
      resorption, and thus was of great potential in the rebuilding of alveolar bone.

PMID- 21731458
TI  - Simultaneous structural identification of natural products in fractions of crude
      extract of the rare endangered plant Anoectochilus roxburghii using H NMR/RRLC-MS
      parallel dynamic spectroscopy.
AB  - Nuclear magnetic resonance/liquid chromatography-mass spectroscopy parallel
      dynamic spectroscopy (NMR/LC-MS PDS) is a method aimed at the simultaneous
      structural identification of natural products in complex mixtures. In this study,
      the method is illustrated with respect to (1)H NMR and rapid resolution liquid
      chromatography-mass spectroscopy (RRLC-MS) data, acquired from the crude extract
      of Anoectochilus roxburghii, which was separated into a series of fractions with
      the concentration of constituent dynamic variation using reversed-phase
      preparative chromatography. Through fraction ranges and intensity changing
      profiles in (1)H NMR/RRLC-MS PDS spectrum, (1)H NMR and the extracted ion
      chromatogram (XIC) signals deriving from the same individual constituent, were
      correlated due to the signal amplitude co-variation resulting from the
      concentration variation of constituents in a series of incompletely separated
      fractions. 1H NMR/RRLC-MS PDS was then successfully used to identify three types
      of natural products, including eight flavonoids, four organic acids and p
      hydroxybenzaldehyde, five of which have not previously been reported in
      Anoectochilus roxburghii. In addition, two groups of co-eluted compounds were
      successfully identified. The results prove that this approach should be of
      benefit in the unequivocal structural determination of a variety of classes of
      compounds from extremely complex mixtures, such as herbs and biological samples,
      which will lead to improved efficiency in the identification of new potential
      lead compounds.

PMID- 21731459
TI  - Droplets formation and merging in two-phase flow microfluidics.
AB  - Two-phase flow microfluidics is emerging as a popular technology for a wide range
      of applications involving high throughput such as encapsulation, chemical
      synthesis and biochemical assays. Within this platform, the formation and merging
      of droplets inside an immiscible carrier fluid are two key procedures: (i) the
      emulsification step should lead to a very well controlled drop size
      (distribution); and (ii) the use of droplet as micro-reactors requires a reliable
      merging. A novel trend within this field is the use of additional active means of
      control besides the commonly used hydrodynamic manipulation. Electric fields are
      especially suitable for this, due to quantitative control over the amplitude and
      time dependence of the signals, and the flexibility in designing micro-electrode
      geometries. With this, the formation and merging of droplets can be achieved on
      demand and with high precision. In this review on two-phase flow microfluidics,
      particular emphasis is given on these aspects. Also recent innovations in
      microfabrication technologies used for this purpose will be discussed.

PMID- 21731460
TI  - Effect of temperature on the physico-chemical properties of a room temperature
      ionic liquid (1-Methyl-3-pentylimidazolium hexafluorophosphate) with polyethylene
      glycol oligomer.
AB  - A systematic study of the effect of composition on the thermo-physical properties
      of the binary mixtures of 1-methyl-3-pentyl imidazolium hexafluorophosphate
      [MPI][PF(6)] with poly(ethylene glycol) (PEG) [M(w) = 400] is presented. The
      excess molar volume, refractive index deviation, viscosity deviation, and surface
      tension deviation values were calculated from these experimental density, rho,
      refractive index, n, viscosity, eta, and surface tension, gamma, over the whole
      concentration range, respectively. The excess molar volumes are negative and
      continue to become increasingly negative with increasing temperature; whereas the
      viscosity and surface tension deviation are negative and become less negative
      with increasing temperature. The surface thermodynamic functions, such as surface
      entropy, enthalpy, as well as standard molar entropy, Parachor, and molar
      enthalpy of vaporization for pure ionic liquid, have been derived from the
      temperature dependence of the surface tension values.

PMID- 21731461
TI  - Antioxidant effects of the ethanol extract from flower of Camellia japonica via
      scavenging of reactive oxygen species and induction of antioxidant enzymes.
AB  - The aim of this study was to investigate the antioxidant properties of the
      ethanol extract of the flower of Camellia japonica (Camellia extract). Camellia
      extract exhibited 1,1-diphenyl-2-picrylhydrazyl radical and intracellular
      reactive oxygen species (ROS) scavenging activity in human HaCaT keratinocytes.
      In addition, Camellia extract scavenged superoxide anion generated by
      xanthine/xanthine oxidase and hydroxyl radical generated by the Fenton reaction
      (FeSO(4) + H(2)O(2)) in a cell-free system, which was detected by electron spin
      resonance spectrometry. Furthermore, Camellia extract increased the protein
      expressions and activity of cellular antioxidant enzymes, such as superoxide
      dismutase, catalase and glutathione peroxidase. These results suggest that
      Camellia extract exhibits antioxidant properties by scavenging ROS and enhancing
      antioxidant enzymes. Camellia extract contained quercetin, quercetin-3-O
      glucoside, quercitrin and kaempferol, which are antioxidant compounds.

PMID- 21731462
TI  - Assessment of acetylcholinesterase activity using indoxylacetate and comparison
      with the standard Ellman's method.
AB  - Assay of acetylcholinesterase (AChE) activity plays an important role in
      diagnostic, detection of pesticides and nerve agents, in vitro characterization
      of toxins and drugs including potential treatments for Alzheimer's disease. These
      experiments were done in order to determine whether indoxylacetate could be an
      adequate chromogenic reactant for AChE assay evaluation. Moreover, the results
      were compared to the standard Ellman's method. We calculated Michaelis constant
      Km (2.06 * 10(-4) mol/L for acetylthiocholine and 3.21 * 10(-3) mol/L for
      indoxylacetate) maximum reaction velocity V(max) (4.97 * 10(-7) kat for
      acetylcholine and 7.71 * 10(-8) kat for indoxylacetate) for electric eel AChE. In
      a second part, inhibition values were plotted for paraoxon, and reactivation
      efficacy was measured for some standard oxime reactivators: obidoxime,
      pralidoxime (2-PAM) and HI-6. Though indoxylacetate is split with lower turnover
      rate, this compound appears as a very attractive reactant since it does not show
      any chemical reactivity with oxime antidots and thiol used for the Ellman's
      method. Thus it can be advantageously used for accurate measurement of AChE
      activity. Suitability of assay for butyrylcholinesterase activity assessment is
      also discussed.

PMID- 21731463
TI  - Infrared assisted production of 3,4-dihydro-2(1H)-pyridones in solvent-free
      conditions.
AB  - A green approach for the synthesis of a set of ten 4-aryl substituted-5-alcoxy
      carbonyl-6-methyl-3,4-dihydro-2(1H)-pyridones using Meldrum's acid has been
      devised, the absence of solvent and the activation with infrared irradiation in
      addition to a multicomponent protocol are the main reaction conditions. The
      transformations proceeded with moderated yields (50-75%) with a reasonable
      reaction rate (3 h). It is worth noting that two novel molecules of the new class
      of the bis-3,4-dihydropyridones were also obtained. In addition, a comparison
      without the use of infrared irradiation was performed.

PMID- 21731464
TI  - In vivo anti-tumor activity of polypeptide HM-3 modified by different
      polyethylene glycols (PEG).
AB  - HM-3, designed by our laboratory, is a polypeptide composed of 18 amino acids.
      Pharmacodynamic studies in vivo and in vitro indicated that HM-3 could inhibit
      endothelial cell migration and angiogenesis, thereby inhibiting tumor growth.
      However, the half-life of HM-3 is short. In this study, we modified HM-3 with
      different polyethylene glycols (PEG) in order to reduce the plasma clearance
      rate, extend the half-life in the body, maintain a high concentration of HM-3 in
      the blood and increase the therapeutic efficiency. HM-3 was modified with four
      different types of PEG with different molecular weights (ALD-mPEG(5k), ALD
      mPEG(10k), SC-mPEG(10k) and SC-mPEG(20k)), resulting in four modified products
      (ALD-mPEG(5k)-HM-3, ALD-mPEG(10k)-HM-3, SC-mPEG(10k)-HM-3 and SC-mPEG(20k)-HM-3,
      respectively). Anti-tumor activity of these four modified HM-3 was determined in
      BALB/c mice with Taxol as a positive control and normal saline as a negative
      control. Tumor weight inhibition rates of mice treated with Taxol, HM-3, ALD
      mPEG(5k)-HM-3, ALD-mPEG(10k)-HM-3, SC-mPEG(10k)-HM-3 and SC-mPEG(20k)-HM-3 were
      44.50%, 43.92%, 37.95%, 31.64%, 20.27% and 50.23%, respectively. Tumor inhibition
      rates in the Taxol, HM-3 and SC-mPEG(20k)-HM-3 groups were significantly higher
      than that in the negative control group. The efficiency of tumor inhibition in
      the SC-mPEG(20k)-HM-3 group (drug treatment frequency: once per two days) was
      better than that in the HM-3 group (drug treatment frequency: twice per day). In
      addition, tumor inhibition rate in the SC-mPEG(20k)-HM-3 group was higher than
      that in the taxol group. We conclude that SC-mPEG(20k)-HM-3 had a low plasma
      clearance rate and long half-life, resulting in high anti-tumor therapeutic
      efficacy in vivo. Therefore, SC-mPEG(20k)-HM-3 could be potentially developed as
      new anti-tumor drugs.

PMID- 21731465
TI  - Genetic variation in safflower (Carthamus tinctorious L.) for seed quality
      related traits and inter-simple sequence repeat (ISSR) markers.
AB  - Safflower (Carthamus tinctorious L.) is an oilseed crop that is valued as a
      source of high quality vegetable oil. The genetic diversity of 16 safflower
      genotypes originated from different geographical regions of Iran and some with
      exotic origin were evaluated. Eight different seed quality-related traits
      including fatty acid composition of seed oil (stearic acid, palmitic acid, oleic
      acid and linoleic acid), the contents of, oil, protein, fiber and ash in its
      seeds, as well as 20 inter-simple sequence repeat (ISSR) polymorphic primers were
      used in this study. Analysis of variance showed significant variation in
      genotypes for the seed quality-related traits. Based on ISSR markers, a total of
      204 bands were amplified and 149 bands (about 70%) of these were polymorphic.
      Cluster analysis based on either biochemical or molecular markers classified the
      genotypes into four groups, showing some similarities between molecular and
      biochemical markers for evaluated genotypes. A logical similarity between the
      genotype clusters based on molecular data with their geographical origins was
      observed.

PMID- 21731466
TI  - Preparation and physicochemical properties of 10-hydroxycamptothecin (HCPT)
      nanoparticles by supercritical antisolvent (SAS) process.
AB  - The goal of the present work was to study the feasibility of 10
      hydroxycamptothecin (HCPT) nanoparticle preparation using supercritical
      antisolvent (SAS) precipitation. The influences of various experimental factors
      on the mean particle size (MPS) of HCPT nanoparticles were investigated. The
      optimum micronization conditions are determined as follows: HCPT solution
      concentration 0.5 mg/mL, the flow rate ratio of CO(2) and HCPT solution 19.55,
      precipitation temperature 35  degrees C and precipitation pressure 20 MPa. Under
      the optimum conditions, HCPT nanoparticles with a MPS of 180 +/- 20.3 nm were
      obtained. Moreover, the HCPT nanoparticles obtained were characterized by
      Scanning electron microscopy, Dynamic light scattering, Fourier-transform
      infrared spectroscopy, High performance liquid chromatography-mass spectrometry,
      X-ray diffraction and Differential scanning calorimetry analyses. The
      physicochemical characterization results showed that the SAS process had not
      induced degradation of HCPT. Finally, the dissolution rates of HCPT nanoparticles
      were investigated and the results proved that there is a significant increase in
      dissolution rate compared to unprocessed HCPT.

PMID- 21731468
TI  - Antimicrobial activities of hexane extract and decussatin from stembark extract
      of Ficus congensis.
AB  - Ficus congensis (Moraceae) is used traditionally in the treatment of various
      diseases including infectious diseases, infertility, and gastrointestinal
      disorders. Investigation of hexane extract of the stem bark using chromatographic
      techniques led to isolation of a xanthone, 1-hydroxy-3,7,8-trimethoxyxanthone
      (Decussatin). The compound was elucidated based on spectroscopic methods such as
      nuclear magnetic resonance (NMR), UV, IR, and mass spectrometry (MS). Decussatin
      and the hexane extract were screened in vitro for antibacterial and antifungal
      activities using broth microdilution (MHB) and disc Agar diffusion (DAD)
      techniques against Escheichia coli, Bacilus substilis, Klebsiela pneumonia,
      Staphylococcus aureus, Aspergillus fumigatus, Trichophyton mentagrophytes,
      Trichophyton rubrum and Candida albicans. Hexane extracts showed potent
      antibacterial activity against E. coli and B. subtilis with minimum inhibitory
      concentrations (MIC) of 8 mg/mL and 5 mg/mL, respectively, while Decussatin of
      the highest concentration (8 mg/mL) used in this study showed no appreciable
      antimicrobial activity. Only hexane extract was active against C. albicans with a
      MIC of 1 mg/mL.

PMID- 21731467
TI  - Database survey of anti-inflammatory plants in South America: a review.
AB  - Inflammation is a complex event linked to tissue damage whether by bacteria,
      physical trauma, chemical, heat or any other phenomenon. This physiological
      response is coordinated largely by a variety of chemical mediators that are
      released from the epithelium, the immunocytes and nerves of the lamina propria.
      However, if the factor that triggers the inflammation persists, the inflammation
      can become relentless, leading to an intensification of the lesion. The present
      work is a literature survey of plant extracts from the South American continent
      that have been reported to show anti-inflammatory activity. This review refers to
      63 bacterial families of which the following stood out: Asteraceae, Fabaceae,
      Euphorbiaceae, Apocynaceae and Celastraceae, with their countries, parts used,
      types of extract used, model bioassays, organisms tested and their activity.

PMID- 21731469
TI  - Antimicrobial, cytotoxic and antioxidant activities and determination of the
      total tannin content of bark extracts Endopleura uchi.
AB  - Endopleura uchi is a typical Amazonian tree and its bark is popularly employed in
      the preparation of teas against myomas, arthritis, influenza, diarrhea and
      cancer. In this study, the antioxidant activity, cytotoxicity and antimicrobial
      activity of five different extracts of the bark, selected by their total tannin
      content, were assessed. The potential antioxidant activity of the extracts was
      determined by 2.2-diphenyl-1-picrylhydrazyl radical scavenging assay and the
      values found were very similar among the extracts and to the standards
      antioxidants used in the tests. Cytotoxicity analysis in mammalian cells
      indicated that all the tested extracts exhibited IC(50) values higher than the
      highest concentration used, showing that they do not present a risk when consumed
      under these conditions. Extract tested against five bacterial strains and one
      yeast strain did not show satisfactory growth inhibitory activity, and even the
      extracts that showed some antimicrobial activity were not effective at any
      dilution to determine the minimum inhibitory concentration. The results may serve
      as a reference for subsequent works, since such reference values described in the
      literature for the bark of E. uchi.

PMID- 21731470
TI  - Functional abdominal pain and irritable bowel syndrome in children and
      adolescents.
AB  - Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are both
      associated with recurrent abdominal pain and are among the most commonly
      diagnosed medical problems in pediatrics. The majority of patients with mild
      complaints improve with reassurance and time. For a distinct subset of patients
      with more severe and disabling illness, finding effective treatment for these
      disorders remains a challenge. Based on the biopsychosocial model of functional
      disease, the Rome III criteria have helped frame FAP and IBS in terms of being a
      positive diagnosis and not a diagnosis of exclusion. However, the lack of a
      single, proven intervention highlights the complex interplay of pathologic
      mechanisms likely involved in the development of childhood FAP and IBS and the
      need for a multidisciplinary, integrated approach. This article discusses the
      epidemiology, proposed mechanisms, clinical approach and therapeutic options for
      the management of FAP and IBS in children and adolescents.

PMID- 21731471
TI  - Modeling neurological diseases using patient-derived induced pluripotent stem
      cells.
AB  - Reprogramming of somatic cells to an embryonic-like state has dramatically
      changed the landscape of stem cell research. Although still in its formative
      stages, the field of induced pluripotent stem cells (iPSCs) has the potential to
      advance the study of neurodegenerative and neurodevelopmental disorders at the
      molecular and cellular levels. The iPSC technology could be employed to establish
      in vitro experimental model systems for the identification of molecular lesions
      and to aid in the discovery of therapeutic targets and effective compounds. The
      derivation of patient-specific iPSCs has also opened up the possibility of
      generating disease-relevant cells for toxicity screening and for cellular
      therapy. In this article, we review the recent progress in the use of disease
      specific iPSCs for in vitro and in vivo modeling of neurological diseases.

PMID- 21731472
TI  - The Interplay Between Parental Beliefs about Children's Emotions and Parental
      Stress Impacts Children's Attachment Security.
AB  - This study investigated how parental beliefs about children's emotions and
      parental stress relate to children's feelings of security in the parent-child
      relationship. Models predicting direct effects of parental beliefs and parental
      stress, and moderating effects of parental stress on the relationship between
      parental beliefs and children's feelings of security were tested. Participants
      were 85 African American, European American, and Lumbee American Indian 4(th) and
      5(th) grade children and one of their parents. Children reported their feelings
      of security in the parent-child relationship; parents independently reported on
      their beliefs and their stress. Parental stress moderated relationships between
      three of the four parental beliefs about the value of children's emotions and
      children's attachment security. When parent stress was low, parental beliefs
      accepting and valuing children's emotions were not related to children's feelings
      of security; when parent stress was high, however, parental beliefs accepting and
      valuing children's emotions were related to children's feelings of security.
      These findings highlight the importance of examining parental beliefs and stress
      together for children's attachment security.

PMID- 21731473
TI  - Are Information, Motivation, and Behavioral Skills Linked with HIV-Related Sexual
      Risk among Young Men Who Have Sex with Men?
AB  - Young men who have sex with men are disproportionately affected by HIV/AIDS, yet
      relatively little is known about the most effective theoretical frameworks for
      preventive interventions with this population. This study investigated the fit of
      the Information-Motivation-Behavioral Skills (IMB) model for predicting sexual
      risk among a sample of ethnically diverse young men who have sex with men aged 14
      21. Path analysis results indicated that the IMB model predicted a moderate
      amount of variance in primary and secondary sexual risk for young men who have
      sex with men (r(2) = .26 and .21, respectively). Fit of this model was acceptable
      on most indicators of model fit for primary and secondary risk.

PMID- 21731474
TI  - More and better information to tackle HIV epidemics: towards improved HIV
      incidence assays.

PMID- 21731475
TI  - Luteolin Regulation of Estrogen Signaling and Cell Cycle Pathway Genes in MCF-7
      Human Breast Cancer Cells.
AB  - cRNA microarray and real-time PCR (qPCR) studies identified a number of Estrogen
      Signaling Pathway (ESP) genes (GTF2H2, NCOR1, TAF9, NRAS, NRIP1, POLR2A, DDX5,
      NCOA3) and Cell Cycle Pathway genes (CCNA2, PCNA, CDKN1A, CCND1, PLK1) in MCF-7
      breast cancer cells that are regulated by the bioflavonoid luteolin. Chromatin
      immunoprecipitation (ChIP) studies revealed that luteolin modified histone H4
      acetylation at the PLK-1 promoter suggesting that this bioflavonoid controls gene
      transcription via an epigenetic mechanism involving histone H4 acetylation. These
      findings are consistent with the anti-estrogenic and anti-proliferative
      properties of luteolin in normal and malignant cells.

PMID- 21731476
TI  - The binding of learning to action in motor adaptation.
AB  - In motor tasks, errors between planned and actual movements generally result in
      adaptive changes which reduce the occurrence of similar errors in the future. It
      has commonly been assumed that the motor adaptation arising from an error
      occurring on a particular movement is specifically associated with the motion
      that was planned. Here we show that this is not the case. Instead, we demonstrate
      the binding of the adaptation arising from an error on a particular trial to the
      motion experienced on that same trial. The formation of this association means
      that future movements planned to resemble the motion experienced on a given trial
      benefit maximally from the adaptation arising from it. This reflects the idea
      that actual rather than planned motions are assigned 'credit' for motor errors
      because, in a computational sense, the maximal adaptive response would be
      associated with the condition credited with the error. We studied this process by
      examining the patterns of generalization associated with motor adaptation to
      novel dynamic environments during reaching arm movements in humans. We found that
      these patterns consistently matched those predicted by adaptation associated with
      the actual rather than the planned motion, with maximal generalization observed
      where actual motions were clustered. We followed up these findings by showing
      that a novel training procedure designed to leverage this newfound understanding
      of the binding of learning to action, can improve adaptation rates by greater
      than 50%. Our results provide a mechanistic framework for understanding the
      effects of partial assistance and error augmentation during neurologic
      rehabilitation, and they suggest ways to optimize their use.

PMID- 21731477
TI  - Dynamic structure formation of peripheral membrane proteins.
AB  - Using coarse-grained membrane simulations we show here that peripheral membrane
      proteins can form a multitude of higher-order structures due to membrane-mediated
      interactions. Peripheral membrane proteins characteristically perturb the lipid
      bilayer in their vicinity which supports the formation of protein assemblies not
      only within the same but surprisingly also across opposing leaflets of a bilayer.
      In addition, we also observed the formation of lipid-protein domains on
      heteregeneous membranes. The clustering ability of proteins, as quantified via
      the potential of mean force, is enhanced when radius and hydrophobic penetration
      depth of the proteins increases. Based on our data, we propose that membrane
      mediated cluster formation of peripheral proteins supports protein assembly in
      vivo and hence may play a pivotal role in the formation of templates for
      signaling cascades and in the emergence of transport intermediates in the
      secretory pathway.

PMID- 21731478
TI  - The origin of behavioral bursts in decision-making circuitry.
AB  - From ants to humans, the timing of many animal behaviors comes in bursts of
      activity separated by long periods of inactivity. Recently, mathematical modeling
      has shown that simple algorithms of priority-driven behavioral choice can result
      in bursty behavior. To experimentally test this link between decision-making
      circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have
      found that the statistics of intervals between activity periods in endogenous
      activity-rest switches of wild-type Drosophila are very well described by the
      Weibull distribution, a common distribution of bursty dynamics in complex
      systems. The bursty dynamics of wild-type Drosophila walking activity are shown
      to be determined by this inter-event distribution alone and not by memory
      effects, thus resembling human dynamics. Further, using mutant flies that disrupt
      dopaminergic signaling or the mushroom body, circuitry implicated in decision
      making, we show that the degree of behavioral burstiness can be modified. These
      results are thus consistent with the proposed link between decision-making
      circuitry and bursty dynamics, and highlight the importance of using simple
      experimental systems to test general theoretical models of behavior. The findings
      further suggest that analysis of bursts could prove useful for the study and
      evaluation of decision-making circuitry.

PMID- 21731479
TI  - Generative embedding for model-based classification of fMRI data.
AB  - Decoding models, such as those underlying multivariate classification algorithms,
      have been increasingly used to infer cognitive or clinical brain states from
      measures of brain activity obtained by functional magnetic resonance imaging
      (fMRI). The practicality of current classifiers, however, is restricted by two
      major challenges. First, due to the high data dimensionality and low sample size,
      algorithms struggle to separate informative from uninformative features,
      resulting in poor generalization performance. Second, popular discriminative
      methods such as support vector machines (SVMs) rarely afford mechanistic
      interpretability. In this paper, we address these issues by proposing a novel
      generative-embedding approach that incorporates neurobiologically interpretable
      generative models into discriminative classifiers. Our approach extends previous
      work on trial-by-trial classification for electrophysiological recordings to
      subject-by-subject classification for fMRI and offers two key advantages over
      conventional methods: it may provide more accurate predictions by exploiting
      discriminative information encoded in 'hidden' physiological quantities such as
      synaptic connection strengths; and it affords mechanistic interpretability of
      clinical classifications. Here, we introduce generative embedding for fMRI using
      a combination of dynamic causal models (DCMs) and SVMs. We propose a general
      procedure of DCM-based generative embedding for subject-wise classification,
      provide a concrete implementation, and suggest good-practice guidelines for
      unbiased application of generative embedding in the context of fMRI. We
      illustrate the utility of our approach by a clinical example in which we classify
      moderately aphasic patients and healthy controls using a DCM of thalamo-temporal
      regions during speech processing. Generative embedding achieves a near-perfect
      balanced classification accuracy of 98% and significantly outperforms
      conventional activation-based and correlation-based methods. This example
      demonstrates how disease states can be detected with very high accuracy and, at
      the same time, be interpreted mechanistically in terms of abnormalities in
      connectivity. We envisage that future applications of generative embedding may
      provide crucial advances in dissecting spectrum disorders into physiologically
      more well-defined subgroups.

PMID- 21731480
TI  - Predicting binding to p-glycoprotein by flexible receptor docking.
AB  - P-glycoprotein (P-gp) is an ATP-dependent transport protein that is selectively
      expressed at entry points of xenobiotics where, acting as an efflux pump, it
      prevents their entering sensitive organs. The protein also plays a key role in
      the absorption and blood-brain barrier penetration of many drugs, while its
      overexpression in cancer cells has been linked to multidrug resistance in tumors.
      The recent publication of the mouse P-gp crystal structure revealed a large and
      hydrophobic binding cavity with no clearly defined sub-sites that supports an
      "induced-fit" ligand binding model. We employed flexible receptor docking to
      develop a new prediction algorithm for P-gp binding specificity. We tested the
      ability of this method to differentiate between binders and nonbinders of P-gp
      using consistently measured experimental data from P-gp efflux and calcein
      inhibition assays. We also subjected the model to a blind test on a series of
      peptidic cysteine protease inhibitors, confirming the ability to predict
      compounds more likely to be P-gp substrates. Finally, we used the method to
      predict cellular metabolites that may be P-gp substrates. Overall, our results
      suggest that many P-gp substrates bind deeper in the cavity than the cyclic
      peptide in the crystal structure and that specificity in P-gp is better
      understood in terms of physicochemical properties of the ligands (and the binding
      site), rather than being defined by specific sub-sites.

PMID- 21731481
TI  - Robust network topologies for generating switch-like cellular responses.
AB  - Signaling networks that convert graded stimuli into binary, all-or-none cellular
      responses are critical in processes ranging from cell-cycle control to lineage
      commitment. To exhaustively enumerate topologies that exhibit this switch-like
      behavior, we simulated all possible two- and three-component networks on random
      parameter sets, and assessed the resulting response profiles for both steepness
      (ultrasensitivity) and extent of memory (bistability). Simulations were used to
      study purely enzymatic networks, purely transcriptional networks, and hybrid
      enzymatic/transcriptional networks, and the topologies in each class were rank
      ordered by parametric robustness (i.e., the percentage of applied parameter sets
      exhibiting ultrasensitivity or bistability). Results reveal that the distribution
      of network robustness is highly skewed, with the most robust topologies
      clustering into a small number of motifs. Hybrid networks are the most robust in
      generating ultrasensitivity (up to 28%) and bistability (up to 18%); strikingly,
      a purely transcriptional framework is the most fragile in generating either
      ultrasensitive (up to 3%) or bistable (up to 1%) responses. The disparity in
      robustness among the network classes is due in part to zero-order
      ultrasensitivity, an enzyme-specific phenomenon, which repeatedly emerges as a
      particularly robust mechanism for generating nonlinearity and can act as a
      building block for switch-like responses. We also highlight experimentally
      studied examples of topologies enabling switching behavior, in both native and
      synthetic systems, that rank highly in our simulations. This unbiased approach
      for identifying topologies capable of a given response may be useful in
      discovering new natural motifs and in designing robust synthetic gene networks.

PMID- 21731482
TI  - Changes of mind in an attractor network of decision-making.
AB  - Attractor networks successfully account for psychophysical and neurophysiological
      data in various decision-making tasks. Especially their ability to model
      persistent activity, a property of many neurons involved in decision-making,
      distinguishes them from other approaches. Stable decision attractors are,
      however, counterintuitive to changes of mind. Here we demonstrate that a
      biophysically-realistic attractor network with spiking neurons, in its itinerant
      transients towards the choice attractors, can replicate changes of mind observed
      recently during a two-alternative random-dot motion (RDM) task. Based on the
      assumption that the brain continues to evaluate available evidence after the
      initiation of a decision, the network predicts neural activity during changes of
      mind and accurately simulates reaction times, performance and percentage of
      changes dependent on difficulty. Moreover, the model suggests a low decision
      threshold and high incoming activity that drives the brain region involved in the
      decision-making process into a dynamical regime close to a bifurcation, which up
      to now lacked evidence for physiological relevance. Thereby, we further affirmed
      the general conformance of attractor networks with higher level neural processes
      and offer experimental predictions to distinguish nonlinear attractor from linear
      diffusion models.

PMID- 21731483
TI  - An evolutionary trade-off between protein turnover rate and protein aggregation
      favors a higher aggregation propensity in fast degrading proteins.
AB  - We previously showed the existence of selective pressure against protein
      aggregation by the enrichment of aggregation-opposing 'gatekeeper' residues at
      strategic places along the sequence of proteins. Here we analyzed the
      relationship between protein lifetime and protein aggregation by combining
      experimentally determined turnover rates, expression data, structural data and
      chaperone interaction data on a set of more than 500 proteins. We find that
      selective pressure on protein sequences against aggregation is not homogeneous
      but that short-living proteins on average have a higher aggregation propensity
      and fewer chaperone interactions than long-living proteins. We also find that
      short-living proteins are more often associated to deposition diseases. These
      findings suggest that the efficient degradation of high-turnover proteins is
      sufficient to preclude aggregation, but also that factors that inhibit
      proteasomal activity, such as physiological ageing, will primarily affect the
      aggregation of short-living proteins.

PMID- 21731484
TI  - Compensatory T cell responses in IRG-deficient mice prevent sustained Chlamydia
      trachomatis infections.
AB  - The obligate intracellular pathogen Chlamydia trachomatis is the most common
      cause of bacterial sexually transmitted diseases in the United States. In women
      C. trachomatis can establish persistent genital infections that lead to pelvic
      inflammatory disease and sterility. In contrast to natural infections in humans,
      experimentally induced infections with C. trachomatis in mice are rapidly
      cleared. The cytokine interferon-gamma (IFNgamma) plays a critical role in the
      clearance of C. trachomatis infections in mice. Because IFNgamma induces an
      antimicrobial defense system in mice but not in humans that is composed of a
      large family of Immunity Related GTPases (IRGs), we questioned whether mice
      deficient in IRG immunity would develop persistent infections with C. trachomatis
      as observed in human patients. We found that IRG-deficient Irgm1/m3((-/-)) mice
      transiently develop high bacterial burden post intrauterine infection, but
      subsequently clear the infection more efficiently than wildtype mice. We show
      that the delayed but highly effective clearance of intrauterine C. trachomatis
      infections in Irgm1/m3((-/-)) mice is dependent on an exacerbated CD4(+) T cell
      response. These findings indicate that the absence of the predominant murine
      innate effector mechanism restricting C. trachomatis growth inside epithelial
      cells results in a compensatory adaptive immune response, which is at least in
      part driven by CD4(+) T cells and prevents the establishment of a persistent
      infection in mice.

PMID- 21731485
TI  - Candida albicans infection of Caenorhabditis elegans induces antifungal immune
      defenses.
AB  - Candida albicans yeast cells are found in the intestine of most humans, yet this
      opportunist can invade host tissues and cause life-threatening infections in
      susceptible individuals. To better understand the host factors that underlie
      susceptibility to candidiasis, we developed a new model to study antifungal
      innate immunity. We demonstrate that the yeast form of C. albicans establishes an
      intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are
      avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected
      with C. albicans yeast showed that exposure to C. albicans stimulated a rapid
      host response involving 313 genes (124 upregulated and 189 downregulated, ~1.6%
      of the genome) many of which encode antimicrobial, secreted or detoxification
      proteins. Interestingly, the host genes affected by C. albicans exposure
      overlapped only to a small extent with the distinct transcriptional responses to
      the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus,
      indicating that there is a high degree of immune specificity toward different
      bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa
      and S. aureus were strongly over-represented among the genes downregulated during
      C. albicans infection, suggesting that in response to fungal pathogens, nematodes
      selectively repress the transcription of antibacterial immune effectors. A
      similar phenomenon is well known in the plant immune response, but has not been
      described previously in metazoans. Finally, 56% of the genes induced by live C.
      albicans were also upregulated by heat-killed yeast. These data suggest that a
      large part of the transcriptional response to C. albicans is mediated through
      "pattern recognition," an ancient immune surveillance mechanism able to detect
      conserved microbial molecules (so-called pathogen-associated molecular patterns
      or PAMPs). This study provides new information on the evolution and regulation of
      the innate immune response to divergent pathogens and demonstrates that nematodes
      selectively mount specific antifungal defenses at the expense of antibacterial
      responses.

PMID- 21731486
TI  - Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central
      nervous systems.
AB  - Certain microbes invade brain microvascular endothelial cells (BMECs) to breach
      the blood-brain barrier (BBB) and establish central nervous system (CNS)
      infection. Here we use the leading meningitis pathogen group B Streptococcus
      (GBS) together with insect and mammalian infection models to probe a potential
      role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry.
      Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C
      protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS
      adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment
      of GAG expression in flies or mice reduced GBS dissemination into the brain.
      These complementary approaches identify a role for bacterial-GAG interactions in
      the pathogenesis of CNS infection. Our results also highlight how the simpler yet
      genetically conserved Drosophila GAG pathways can provide a model organism to
      screen candidate molecules that can interrupt pathogen-GAG interactions for
      future therapeutic applications.

PMID- 21731487
TI  - The N-terminus of the RNA polymerase from infectious pancreatic necrosis virus is
      the determinant of genome attachment.
AB  - The RNA-dependent RNA polymerase VP1 of infectious pancreatic necrosis virus
      (IPNV) is a single polypeptide responsible for both viral RNA transcription and
      genome replication. Sequence analysis identifies IPNV VP1 as having an unusual
      active site topology. We have purified, crystallized and solved the structure of
      IPNV VP1 to 2.3 A resolution in its apo form and at 2.2 A resolution bound to the
      catalytically-activating metal magnesium. We find that recombinantly-expressed
      VP1 is highly active for RNA transcription and replication, yielding both free
      and polymerase-attached RNA products. IPNV VP1 also possesses terminal
      (deoxy)nucleotide transferase, RNA-dependent DNA polymerase (reverse
      transcriptase) and template-independent self-guanylylation activity. The N
      terminus of VP1 interacts with the active-site cleft and we show that the N
      terminal serine residue is required for formation of covalent RNA:polymerase
      complexes, providing a mechanism for the genesis of viral genome:polymerase
      complexes observed in vivo.

PMID- 21731488
TI  - HIV/SIV infection primes monocytes and dendritic cells for apoptosis.
AB  - Subversion or exacerbation of antigen-presenting cells (APC) death modulates
      host/pathogen equilibrium. We demonstrated during in vitro differentiation of
      monocyte-derived macrophages and monocyte-derived dendritic cells (DCs) that HIV
      sensitizes the cells to undergo apoptosis in response to TRAIL and FasL,
      respectively. In addition, we found that HIV-1 increased the levels of pro
      apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1
      and FLIP proteins. To assess the relevance of these observations in the context
      of an experimental model of HIV infection, we investigated the death of APC
      during pathogenic SIV-infection in rhesus macaques (RMs). We demonstrated
      increased apoptosis, during the acute phase, of both peripheral blood DCs and
      monocytes (CD14(+)) from SIV(+)RMs, associated with a dysregulation in the
      balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death
      receptors antagonists prevented apoptosis of APCs from SIV(+)RMs. Furthermore,
      increased levels of FasL in the sera of pathogenic SIV(+)RMs were detected,
      compared to non-pathogenic SIV infection of African green monkey. We suggest that
      inappropriate apoptosis of antigen-presenting cells may contribute to
      dysregulation of cellular immunity early in the process of HIV/SIV infection.

PMID- 21731489
TI  - The lipid transfer protein CERT interacts with the Chlamydia inclusion protein
      IncD and participates to ER-Chlamydia inclusion membrane contact sites.
AB  - Bacterial pathogens that reside in membrane bound compartment manipulate the host
      cell machinery to establish and maintain their intracellular niche. The hijacking
      of inter-organelle vesicular trafficking through the targeting of small GTPases
      or SNARE proteins has been well established. Here, we show that intracellular
      pathogens also establish direct membrane contact sites with organelles and
      exploit non-vesicular transport machinery. We identified the ER-to-Golgi ceramide
      transfer protein CERT as a host cell factor specifically recruited to the
      inclusion, a membrane-bound compartment harboring the obligate intracellular
      pathogen Chlamydia trachomatis. We further showed that CERT recruitment to the
      inclusion correlated with the recruitment of VAPA/B-positive tubules in close
      proximity of the inclusion membrane, suggesting that ER-Inclusion membrane
      contact sites are formed upon C. trachomatis infection. Moreover, we identified
      the C. trachomatis effector protein IncD as a specific binding partner for CERT.
      Finally we showed that depletion of either CERT or the VAP proteins impaired
      bacterial development. We propose that the presence of IncD, CERT, VAPA/B, and
      potentially additional host and/or bacterial factors, at points of contact
      between the ER and the inclusion membrane provides a specialized metabolic and/or
      signaling microenvironment favorable to bacterial development.

PMID- 21731491
TI  - Evolutionary analysis of inter-farm transmission dynamics in a highly pathogenic
      avian influenza epidemic.
AB  - Phylogenetic studies have largely contributed to better understand the emergence,
      spread and evolution of highly pathogenic avian influenza during epidemics, but
      sampling of genetic data has never been detailed enough to allow mapping of the
      spatiotemporal spread of avian influenza viruses during a single epidemic. Here,
      we present genetic data of H7N7 viruses produced from 72% of the poultry farms
      infected during the 2003 epidemic in the Netherlands. We use phylogenetic
      analyses to unravel the pathways of virus transmission between farms and between
      infected areas. In addition, we investigated the evolutionary processes shaping
      viral genetic diversity, and assess how they could have affected our phylogenetic
      analyses. Our results show that the H7N7 virus was characterized by a high level
      of genetic diversity driven mainly by a high neutral substitution rate, purifying
      selection and limited positive selection. We also identified potential
      reassortment in the three genes that we have tested, but they had only a limited
      effect on the resolution of the inter-farm transmission network. Clonal
      sequencing analyses performed on six farm samples showed that at least one farm
      sample presented very complex virus diversity and was probably at the origin of
      chronological anomalies in the transmission network. However, most virus
      sequences could be grouped within clearly defined and chronologically sound
      clusters of infection and some likely transmission events between farms located
      0.8-13 Km apart were identified. In addition, three farms were found as most
      likely source of virus introduction in distantly located new areas. These long
      distance transmission events were likely facilitated by human-mediated transport,
      underlining the need for strict enforcement of biosafety measures during
      outbreaks. This study shows that in-depth genetic analysis of virus outbreaks at
      multiple scales can provide critical information on virus transmission dynamics
      and can be used to increase our capacity to efficiently control epidemics.

PMID- 21731490
TI  - Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets
      and acquires a dormancy-like phenotype in lipid-loaded macrophages.
AB  - Two billion people are latently infected with Mycobacterium tuberculosis (Mtb).
      Mtb-infected macrophages are likely to be sequestered inside the hypoxic
      environments of the granuloma and differentiate into lipid-loaded macrophages
      that contain triacylglycerol (TAG)-filled lipid droplets which may provide a
      fatty acid-rich host environment for Mtb. We report here that human peripheral
      blood monocyte-derived macrophages and THP-1 derived macrophages incubated under
      hypoxia accumulate Oil Red O-staining lipid droplets containing TAG. Inside such
      hypoxic, lipid-loaded macrophages, nearly half the Mtb population developed
      phenotypic tolerance to isoniazid, lost acid-fast staining and accumulated
      intracellular lipid droplets. Dual-isotope labeling of macrophage TAG revealed
      that Mtb inside the lipid-loaded macrophages imports fatty acids derived from
      host TAG and incorporates them intact into Mtb TAG. The fatty acid composition of
      host and Mtb TAG were nearly identical suggesting that Mtb utilizes host TAG to
      accumulate intracellular TAG. Utilization of host TAG by Mtb for lipid droplet
      synthesis was confirmed when fluorescent fatty acid-labeled host TAG was utilized
      to accumulate fluorescent lipid droplets inside the pathogen. Deletion of the Mtb
      triacylglycerol synthase 1 (tgs1) gene resulted in a drastic decrease but not a
      complete loss in both radiolabeled and fluorescent TAG accumulation by Mtb
      suggesting that the TAG that accumulates within Mtb is generated mainly by the
      incorporation of fatty acids released from host TAG. We show direct evidence for
      the utilization of the fatty acids from host TAG for lipid metabolism inside Mtb.
      Taqman real-time PCR measurements revealed that the mycobacterial genes dosR,
      hspX, icl1, tgs1 and lipY were up-regulated in Mtb within hypoxic lipid loaded
      macrophages along with other Mtb genes known to be associated with dormancy and
      lipid metabolism.

PMID- 21731492
TI  - Insertion of an esterase gene into a specific locust pathogen (Metarhizium
      acridum) enables it to infect caterpillars.
AB  - An enduring theme in pathogenic microbiology is poor understanding of the
      mechanisms of host specificity. Metarhizium is a cosmopolitan genus of
      invertebrate pathogens that contains generalist species with broad host ranges
      such as M. robertsii (formerly known as M. anisopliae var. anisopliae) as well as
      specialists such as the acridid-specific grasshopper pathogen M. acridum. During
      growth on caterpillar (Manduca sexta) cuticle, M. robertsii up-regulates a gene
      (Mest1) that is absent in M. acridum and most other fungi. Disrupting M.
      robertsii Mest1 reduced virulence and overexpression increased virulence to
      caterpillars (Galleria mellonella and M. sexta), while virulence to grasshoppers
      (Melanoplus femurrubrum) was unaffected. When Mest1 was transferred to M. acridum
      under control of its native M. robertsii promoter, the transformants killed and
      colonized caterpillars in a similar fashion to M. robertsii. MEST1 localized
      exclusively to lipid droplets in M. robertsii conidia and infection structures
      was up-regulated during nutrient deprivation and had esterase activity against
      lipids with short chain fatty acids. The mobilization of stored lipids was
      delayed in the Mest1 disruptant mutant. Overall, our results suggest that
      expression of Mest1 allows rapid hydrolysis of stored lipids, and promotes
      germination and infection structure formation by M. robertsii during nutrient
      deprivation and invasion, while Mest1 expression in M. acridum broadens its host
      range by bypassing the regulatory signals found on natural hosts that trigger the
      mobilization of endogenous nutrient reserves. This study suggests that speciation
      in an insect pathogen could potentially be driven by host shifts resulting from
      changes in a single gene.

PMID- 21731493
TI  - Highly pathogenic avian influenza virus H5N1 infects alveolar macrophages without
      virus production or excessive TNF-alpha induction.
AB  - Highly pathogenic avian influenza virus (HPAIV) of the subtype H5N1 causes
      severe, often fatal pneumonia in humans. The pathogenesis of HPAIV H5N1 infection
      is not completely understood, although the alveolar macrophage (AM) is thought to
      play an important role. HPAIV H5N1 infection of macrophages cultured from
      monocytes leads to high percentages of infection accompanied by virus production
      and an excessive pro-inflammatory immune response. However, macrophages cultured
      from monocytes are different from AM, both in phenotype and in response to
      seasonal influenza virus infection. Consequently, it remains unclear whether the
      results of studies with macrophages cultured from monocytes are valid for AM.
      Therefore we infected AM and for comparison macrophages cultured from monocytes
      with seasonal H3N2 virus, HPAIV H5N1 or pandemic H1N1 virus, and determined the
      percentage of cells infected, virus production and induction of TNF-alpha, a pro
      inflammatory cytokine. In vitro HPAIV H5N1 infection of AM compared to that of
      macrophages cultured from monocytes resulted in a lower percentage of infected
      cells (up to 25% vs up to 84%), lower virus production and lower TNF-alpha
      induction. In vitro infection of AM with H3N2 or H1N1 virus resulted in even
      lower percentages of infected cells (up to 7%) than with HPAIV H5N1, while virus
      production and TNF-alpha induction were comparable. In conclusion, this study
      reveals that macrophages cultured from monocytes are not a good model to study
      the interaction between AM and these influenza virus strains. Furthermore, the
      interaction between HPAIV H5N1 and AM could contribute to the pathogenicity of
      this virus in humans, due to the relative high percentage of infected cells
      rather than virus production or an excessive TNF-alpha induction.

PMID- 21731494
TI  - Contribution of intrinsic reactivity of the HIV-1 envelope glycoproteins to CD4
      independent infection and global inhibitor sensitivity.
AB  - Human immunodeficiency virus (HIV-1) enters cells following sequential activation
      of the high-potential-energy viral envelope glycoprotein trimer by target cell
      CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses
      that can infect coreceptor-expressing cells that lack CD4 have been generated in
      the laboratory. These CD4-independent HIV-1 variants are sensitive to
      neutralization by multiple antibodies that recognize different envelope
      glycoprotein epitopes. The mechanisms underlying CD4 independence, global
      sensitivity to neutralization and the association between them are still unclear.
      By studying HIV-1 variants that differ in requirements for CD4, we investigated
      the contribution of CD4 binding to virus entry. CD4 engagement exposes the
      coreceptor-binding site and increases the "intrinsic reactivity" of the envelope
      glycoproteins; intrinsic reactivity describes the propensity of the envelope
      glycoproteins to negotiate transitions to lower-energy states upon stimulation.
      Coreceptor-binding site exposure and increased intrinsic reactivity promote
      formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein
      and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates
      the global sensitivity of HIV-1 to perturbations such as exposure to cold and the
      binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1
      was accompanied by increased susceptibility to inactivation by these factors. We
      investigated the role of intrinsic reactivity in determining the sensitivity of
      primary HIV-1 isolates to inhibition. Relative to the more common neutralization
      resistant ("Tier 2-like") viruses, globally sensitive ("Tier 1") viruses
      exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently
      by cold exposure or by a given level of antibody binding to the envelope
      glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the
      efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and
      by envelope glycoprotein reactivity to the inhibitor/antibody binding event.
      Quantitative differences in intrinsic reactivity contribute to HIV-1 strain
      variability in global susceptibility to neutralization and explain the long
      observed relationship between increased inhibitor sensitivity and decreased entry
      requirements for target cell CD4.

PMID- 21731495
TI  - Low CCR7-mediated migration of human monocyte derived dendritic cells in response
      to human respiratory syncytial virus and human metapneumovirus.
AB  - Human respiratory syncytial virus (HRSV) and, to a lesser extent, human
      metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), can re
      infect symptomatically throughout life without significant antigenic change,
      suggestive of incomplete or short-lived immunity. In contrast, re-infection by
      influenza A virus (IAV) largely depends on antigenic change, suggestive of more
      complete immunity. Antigen presentation by dendritic cells (DC) is critical in
      initiating the adaptive immune response. Antigen uptake by DC induces
      maturational changes that include decreased expression of the chemokine receptors
      CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and
      increased expression of CCR7 that mediates the migration of antigen-bearing DC to
      lymphatic tissue. We stimulated human monocyte-derived DC (MDDC) with virus and
      found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently
      decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7
      expression. Consistent with the differences in CCR7 mRNA and protein expression,
      MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand
      CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we
      showed that the subpopulation of MDDC that was robustly infected with HRSV was
      particularly inefficient in chemokine receptor modulation. HMPV- or HRSV
      stimulated MDDC responded to secondary stimulation with bacterial
      lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing
      CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to
      CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than
      irreversibly inhibit MDDC migration. This also suggests that the low
      concentration of proinflammatory cytokines released from HRSV- and HMPV
      stimulated MDDC is partly responsible for the low CCR7-mediated migration. We
      propose that inefficient migration of HRSV- and HMPV-stimulated DC to lymphatic
      tissue contributes to reduced adaptive responses to these viruses.

PMID- 21731496
TI  - Detection of inferred CCR5- and CXCR4-using HIV-1 variants and evolutionary
      intermediates using ultra-deep pyrosequencing.
AB  - The emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants
      is associated with accelerated disease progression. CXCR4-using variants are
      believed to evolve from CCR5-using variants, but due to the extremely low
      frequency at which transitional intermediate variants are often present, the
      kinetics and mutational pathways involved in this process have been difficult to
      study and are therefore poorly understood. Here, we used ultra-deep sequencing of
      the V3 loop of the viral envelope in combination with the V3-based coreceptor
      prediction tools PSSM(NSI/SI) and geno2pheno([coreceptor]) to detect HIV-1
      variants during the transition from CCR5- to CXCR4-usage. We analyzed PBMC and
      serum samples obtained from eight HIV-1-infected individuals at three-month
      intervals up to one year prior to the first phenotypic detection of CXCR4-using
      variants in the MT-2 assay. Between 3,482 and 10,521 reads were generated from
      each sample. In all individuals, V3 sequences of predicted CXCR4-using HIV-1 were
      detected at least three months prior to phenotypic detection of CXCR4-using
      variants in the MT-2 assay. Subsequent analysis of the genetic relationships of
      these V3 sequences using minimum spanning trees revealed that the transition in
      coreceptor usage followed a stepwise mutational pathway involving sequential
      intermediate variants, which were generally present at relatively low frequencies
      compared to the major predicted CCR5- and CXCR4-using variants. In addition, we
      observed differences between individuals with respect to the number of predicted
      CXCR4-using variants, the diversity among major predicted CCR5-using variants,
      and the presence or absence of intermediate variants with discordant phenotype
      predictions. These results provide the first detailed description of the
      mutational pathways in V3 during the transition from CCR5- to CXCR4-usage in
      natural HIV-1 infection.

PMID- 21731497
TI  - Interferon regulatory factor 8 regulates pathways for antigen presentation in
      myeloid cells and during tuberculosis.
AB  - IRF8 (Interferon Regulatory Factor 8) plays an important role in defenses against
      intracellular pathogens, including several aspects of myeloid cells function. It
      is required for ontogeny and maturation of macrophages and dendritic cells, for
      activation of anti-microbial defenses, and for production of the Th1-polarizing
      cytokine interleukin-12 (IL-12) in response to interferon gamma (IFNgamma) and
      protection against infection with Mycobacterium tuberculosis. The transcriptional
      programs and cellular pathways that are regulated by IRF8 in response to IFNgamma
      and that are important for defenses against M. tuberculosis are poorly
      understood. These were investigated by transcript profiling and chromatin
      immunoprecipitation on microarrays (ChIP-chip). Studies in primary macrophages
      identified 368 genes that are regulated by IRF8 in response to IFNgamma/CpG and
      that behave as stably segregating expression signatures (eQTLs) in F2 mice fixed
      for a wild-type or mutant allele at IRF8. A total of 319 IRF8 binding sites were
      identified on promoters genome-wide (ChIP-chip) in macrophages treated with
      IFNgamma/CpG, defining a functional G/AGAAnTGAAA motif. An analysis of the genes
      bearing a functional IRF8 binding site, and showing regulation by IFNgamma/CpG in
      macrophages and/or in M. tuberculosis-infected lungs, revealed a striking
      enrichment for the pathways of antigen processing and presentation, including
      multiple structural and enzymatic components of the Class I and Class II MHC
      (major histocompatibility complex) antigen presentation machinery. Also
      significantly enriched as IRF8 targets are the group of endomembrane- and
      phagosome-associated small GTPases of the IRG (immunity-related GTPases) and GBP
      (guanylate binding proteins) families. These results identify IRF8 as a key
      regulator of early response pathways in myeloid cells, including phagosome
      maturation, antigen processing, and antigen presentation by myeloid cells.

PMID- 21731498
TI  - A genome-wide survey of imprinted genes in rice seeds reveals imprinting
      primarily occurs in the endosperm.
AB  - Genomic imprinting causes the expression of an allele depending on its parental
      origin. In plants, most imprinted genes have been identified in Arabidopsis
      endosperm, a transient structure consumed by the embryo during seed formation. We
      identified imprinted genes in rice seed where both the endosperm and embryo are
      present at seed maturity. RNA was extracted from embryos and endosperm of seeds
      obtained from reciprocal crosses between two subspecies Nipponbare (Japonica
      rice) and 93-11 (Indica rice). Sequenced reads from cDNA libraries were aligned
      to their respective parental genomes using single-nucleotide polymorphisms
      (SNPs). Reads across SNPs enabled derivation of parental expression bias ratios.
      A continuum of parental expression bias states was observed. Statistical analyses
      indicated 262 candidate imprinted loci in the endosperm and three in the embryo
      (168 genic and 97 non-genic). Fifty-six of the 67 loci investigated were
      confirmed to be imprinted in the seed. Imprinted loci are not clustered in the
      rice genome as found in mammals. All of these imprinted loci were expressed in
      the endosperm, and one of these was also imprinted in the embryo, confirming that
      in both rice and Arabidopsis imprinted expression is primarily confined to the
      endosperm. Some rice imprinted genes were also expressed in vegetative tissues,
      indicating that they have additional roles in plant growth. Comparison of
      candidate imprinted genes found in rice with imprinted candidate loci obtained
      from genome-wide surveys of imprinted genes in Arabidopsis to date shows a low
      degree of conservation, suggesting that imprinting has evolved independently in
      eudicots and monocots.

PMID- 21731499
TI  - Increased susceptibility to cortical spreading depression in the mouse model of
      familial hemiplegic migraine type 2.
AB  - Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant form of
      migraine with aura that is caused by mutations of the alpha2-subunit of the Na,K
      ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain.
      We generated the first FHM2 knock-in mouse model carrying the human W887R
      mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2(R887/R887) mutants
      died just after birth, while heterozygous Atp1a2(+/R887) mice showed no apparent
      clinical phenotype. The mutant alpha2 Na,K-ATPase protein was barely detectable
      in the brain of homozygous mutants and strongly reduced in the brain of
      heterozygous mutants, likely as a consequence of endoplasmic reticulum retention
      and subsequent proteasomal degradation, as we demonstrate in transfected cells.
      In vivo analysis of cortical spreading depression (CSD), the phenomenon
      underlying migraine aura, revealed a decreased induction threshold and an
      increased velocity of propagation in the heterozygous FHM2 mouse. Since several
      lines of evidence involve a specific role of the glial alpha2 Na,K pump in active
      reuptake of glutamate from the synaptic cleft, we hypothesize that CSD
      facilitation in the FHM2 mouse model is sustained by inefficient glutamate
      clearance by astrocytes and consequent increased cortical excitatory
      neurotransmission. The demonstration that FHM2 and FHM1 mutations share the
      ability to facilitate induction and propagation of CSD in mouse models further
      support the role of CSD as a key migraine trigger.

PMID- 21731500
TI  - Graded Nodal/Activin signaling titrates conversion of quantitative phospho-Smad2
      levels into qualitative embryonic stem cell fate decisions.
AB  - Nodal and Activin are morphogens of the TGFbeta superfamily of signaling
      molecules that direct differential cell fate decisions in a dose- and distance
      dependent manner. During early embryonic development the Nodal/Activin pathway is
      responsible for the specification of mesoderm, endoderm, node, and mesendoderm.
      In contradiction to this drive towards cellular differentiation, the pathway also
      plays important roles in the maintenance of self-renewal and pluripotency in
      embryonic and epiblast stem cells. The molecular basis behind stem cell
      interpretation of Nodal/Activin signaling gradients and the undertaking of
      disparate cell fate decisions remains poorly understood. Here, we show that any
      perturbation of endogenous signaling levels in mouse embryonic stem cells leads
      to their exit from self-renewal towards divergent differentiation programs.
      Increasing Nodal signals above basal levels by direct stimulation with Activin
      promotes differentiation towards the mesendodermal lineages while repression of
      signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces
      trophectodermal differentiation. To address how quantitative Nodal/Activin
      signals are translated qualitatively into distinct cell fates decisions, we
      performed chromatin immunoprecipitation of phospho-Smad2, the primary downstream
      transcriptional factor of the Nodal/Activin pathway, followed by massively
      parallel sequencing, and show that phospho-Smad2 binds to and regulates distinct
      subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin
      signaling directly controls the Oct4 master regulator of pluripotency by graded
      phospho-Smad2 binding in the promoter region. Hence stem cells interpret and
      carry out differential Nodal/Activin signaling instructions via a corresponding
      gradient of Smad2 phosphorylation that selectively titrates self-renewal against
      alternative differentiation programs by direct regulation of distinct target gene
      subsets and Oct4 expression.

PMID- 21731501
TI  - Differential gene expression and epiregulation of alpha zein gene copies in maize
      haplotypes.
AB  - Multigenic traits are very common in plants and cause diversity. Nutritional
      quality is such a trait, and one of its factors is the composition and relative
      expression of storage protein genes. In maize, they represent a medium-size gene
      family distributed over several chromosomes and unlinked locations. Two inbreds,
      B73 and BSSS53, both from the Iowa Stiff Stock Synthetic collection, have been
      selected to analyze allelic and non-allelic variability in these regions that
      span between 80-500 kb of chromosomal DNA. Genes were copied to unlinked sites
      before and after allotetraploidization of maize, but before transposition
      enlarged intergenic regions in a haplotype-specific manner. Once genes are
      copied, expression of donor genes is reduced relative to new copies. Epigenetic
      regulation seems to contribute to silencing older copies, because some of them
      can be reactivated when endosperm is maintained as cultured cells, indicating
      that copy number variation might contribute to a reserve of gene copies.
      Bisulfite sequencing of the promoter region also shows different methylation
      patterns among gene clusters as well as differences between tissues, suggesting a
      possible position effect on regulatory mechanisms as a result of inserting copies
      at unlinked locations. The observations offer a potential paradigm for how
      different gene families evolve and the impact this has on their expression and
      regulation of their members.

PMID- 21731502
TI  - Vive la difference: an interview with Catherine Dulac. Interview by Jane
      Gitschier.

PMID- 21731503
TI  - Genomic convergence among ERRalpha, PROX1, and BMAL1 in the control of metabolic
      clock outputs.
AB  - Metabolic homeostasis and circadian rhythms are closely intertwined biological
      processes. Nuclear receptors, as sensors of hormonal and nutrient status, are
      actively implicated in maintaining this physiological relationship. Although the
      orphan nuclear receptor estrogen-related receptor alpha (ERRalpha, NR3B1) plays a
      central role in the control of energy metabolism and its expression is known to
      be cyclic in the liver, its role in temporal control of metabolic networks is
      unknown. Here we report that ERRalpha directly regulates all major components of
      the molecular clock. ERRalpha-null mice also display deregulated locomotor
      activity rhythms and circadian period lengths under free-running conditions, as
      well as altered circulating diurnal bile acid and lipid profiles. In addition,
      the ERRalpha-null mice exhibit time-dependent hypoglycemia and hypoinsulinemia,
      suggesting a role for ERRalpha in modulating insulin sensitivity and glucose
      handling during the 24-hour light/dark cycle. We also provide evidence that the
      newly identified ERRalpha corepressor PROX1 is implicated in rhythmic control of
      metabolic outputs. To help uncover the molecular basis of these phenotypes, we
      performed genome-wide location analyses of binding events by ERRalpha, PROX1, and
      BMAL1, an integral component of the molecular clock. These studies revealed the
      existence of transcriptional regulatory loops among ERRalpha, PROX1, and BMAL1,
      as well as extensive overlaps in their target genes, implicating these three
      factors in the control of clock and metabolic gene networks in the liver. Genomic
      convergence of ERRalpha, PROX1, and BMAL1 transcriptional activity thus
      identified a novel node in the molecular circuitry controlling the daily timing
      of metabolic processes.

PMID- 21731504
TI  - Extracellular matrix dynamics in hepatocarcinogenesis: a comparative proteomics
      study of PDGFC transgenic and Pten null mouse models.
AB  - We are reporting qualitative and quantitative changes of the extracellular matrix
      (ECM) and associated receptor proteomes, occurring during the transition from
      liver fibrosis and steatohepatitis to hepatocellular carcinoma (HCC). We compared
      two mouse models relevant to human HCC: PDGFC transgenic (Tg) and Pten null mice,
      models of disease progression from fibrosis and steatohepatitis to HCC. Using
      mass spectrometry, we identified in the liver of both models proteins for 26
      collagen-encoding genes, providing the first evidence of expression at the
      protein level for 16 collagens. We also identified post-transcriptional protein
      variants for six collagens and lysine hydroxylation modifications for 14
      collagens. Tumor-associated collagen proteomes were similar in both models with
      increased expression of collagens type IV, VI, VII, X, XIV, XV, XVI, and XVIII.
      Splice variants for Col4a2, Col6a2, Col6a3 were co-upregulated while only the
      short form of Col18a1 increased in the tumors. We also identified tumor specific
      increases of nidogen 1, decorin, perlecan, and of six laminin subunits. The
      changes in these non-collagenous ECM proteins were similar in both models with
      the exception of laminin beta3, detected specifically in the Pten null tumors.
      Pdgfa and Pdgfc mRNA expression was increased in the Pten null liver, a possible
      mechanism for the similarity in ECM composition observed in the tumors of both
      models. In contrast and besides the strong up-regulation of integrin alpha5
      protein observed in the liver tumors of both models, the expression of the six
      other integrins identified was specific to each model, with integrins alpha2b,
      alpha3, alpha6, and beta1 up-regulated in Pten null tumors and integrins alpha8
      and beta5 up-regulated in the PDGFC Tg tumors. In conclusion, HCC-associated ECM
      proteins and ECM-integrin networks, common or specific to HCC subtypes, were
      identified, providing a unique foundation to using ECM composition for HCC
      classification, diagnosis, prevention, or treatment.

PMID- 21731505
TI  - Bacteriophage crosstalk: coordination of prophage induction by trans-acting
      antirepressors.
AB  - Many species of bacteria harbor multiple prophages in their genomes. Prophages
      often carry genes that confer a selective advantage to the bacterium, typically
      during host colonization. Prophages can convert to infectious viruses through a
      process known as induction, which is relevant to the spread of bacterial
      virulence genes. The paradigm of prophage induction, as set by the phage Lambda
      model, sees the process initiated by the RecA-stimulated self-proteolysis of the
      phage repressor. Here we show that a large family of lambdoid prophages found in
      Salmonella genomes employs an alternative induction strategy. The repressors of
      these phages are not cleaved upon induction; rather, they are inactivated by the
      binding of small antirepressor proteins. Formation of the complex causes the
      repressor to dissociate from DNA. The antirepressor genes lie outside the
      immunity region and are under direct control of the LexA repressor, thus plugging
      prophage induction directly into the SOS response. GfoA and GfhA, the
      antirepressors of Salmonella prophages Gifsy-1 and Gifsy-3, each target both of
      these phages' repressors, GfoR and GfhR, even though the latter proteins
      recognize different operator sites and the two phages are heteroimmune. In
      contrast, the Gifsy-2 phage repressor, GtgR, is insensitive to GfoA and GfhA, but
      is inactivated by an antirepressor from the unrelated Fels-1 prophage (FsoA).
      This response is all the more surprising as FsoA is under the control of the Fels
      1 repressor, not LexA, and plays no apparent role in Fels-1 induction, which
      occurs via a Lambda CI-like repressor cleavage mechanism. The ability of
      antirepressors to recognize non-cognate repressors allows coordination of
      induction of multiple prophages in polylysogenic strains. Identification of non
      cleavable gfoR/gtgR homologues in a large variety of bacterial genomes (including
      most Escherichia coli genomes in the DNA database) suggests that antirepression
      mediated induction is far more common than previously recognized.

PMID- 21731506
TI  - A new mutation affecting FRQ-less rhythms in the circadian system of Neurospora
      crassa.
AB  - We are using the fungus Neurospora crassa as a model organism to study the
      circadian system of eukaryotes. Although the FRQ/WCC feedback loop is said to be
      central to the circadian system in Neurospora, rhythms can still be seen under
      many conditions in FRQ-less (frq knockout) strains. To try to identify components
      of the FRQ-less oscillator (FLO), we carried out a mutagenesis screen in a FRQ
      less strain and selected colonies with altered conidiation (spore-formation)
      rhythms. A mutation we named UV90 affects rhythmicity in both FRQ-less and FRQ
      sufficient strains. The UV90 mutation affects FRQ-less rhythms in two conditions:
      the free-running long-period rhythm in choline-depleted chol-1 strains becomes
      arrhythmic, and the heat-entrained rhythm in the frq(10) knockout is severely
      altered. In a FRQ-sufficient background, the UV90 mutation causes damping of the
      free-running conidiation rhythm, reduction of the amplitude of the FRQ protein
      rhythm, and increased phase-resetting responses to both light and heat pulses,
      consistent with a decreased amplitude of the circadian oscillator. The UV90
      mutation also has small but significant effects on the period of the conidiation
      rhythm and on growth rate. The wild-type UV90 gene product appears to be required
      for a functional FLO and for sustained, high-amplitude rhythms in FRQ-sufficient
      conditions. The UV90 gene product may therefore be a good candidate for a
      component of the FRQ-less oscillator. These results support a model of the
      Neurospora circadian system in which the FRQ/WCC feedback loop mutually interacts
      with a single FLO in an integrated circadian system.

PMID- 21731507
TI  - Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic
      variability.
AB  - Helicobacter pylori, a human pathogen infecting about half of the world
      population, is characterised by its large intraspecies variability. Its genome
      plasticity has been invoked as the basis for its high adaptation capacity.
      Consistent with its small genome, H. pylori possesses only two bona fide DNA
      polymerases, Pol I and the replicative Pol III, lacking homologues of translesion
      synthesis DNA polymerases. Bacterial DNA polymerases I are implicated both in
      normal DNA replication and in DNA repair. We report that H. pylori DNA Pol I 5'-
      3' exonuclease domain is essential for viability, probably through its
      involvement in DNA replication. We show here that, despite the fact that it also
      plays crucial roles in DNA repair, Pol I contributes to genomic instability.
      Indeed, strains defective in the DNA polymerase activity of the protein, although
      sensitive to genotoxic agents, display reduced mutation frequencies. Conversely,
      overexpression of Pol I leads to a hypermutator phenotype. Although the purified
      protein displays an intrinsic fidelity during replication of undamaged DNA, it
      lacks a proofreading activity, allowing it to efficiently elongate mismatched
      primers and perform mutagenic translesion synthesis. In agreement with this
      finding, we show that the spontaneous mutator phenotype of a strain deficient in
      the removal of oxidised pyrimidines from the genome is in part dependent on the
      presence of an active DNA Pol I. This study provides evidence for an unexpected
      role of DNA polymerase I in generating genomic plasticity.

PMID- 21731508
TI  - Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human
      embryonic stem cells.
AB  - Covalent modification of DNA distinguishes cellular identities and is crucial for
      regulating the pluripotency and differentiation of embryonic stem (ES) cells. The
      recent demonstration that 5-methylcytosine (5-mC) may be further modified to 5
      hydroxymethylcytosine (5-hmC) in ES cells has revealed a novel regulatory
      paradigm to modulate the epigenetic landscape of pluripotency. To understand the
      role of 5-hmC in the epigenomic landscape of pluripotent cells, here we profile
      the genome-wide 5-hmC distribution and correlate it with the genomic profiles of
      11 diverse histone modifications and six transcription factors in human ES cells.
      By integrating genomic 5-hmC signals with maps of histone enrichment, we link
      particular pluripotency-associated chromatin contexts with 5-hmC. Intriguingly,
      through additional correlations with defined chromatin signatures at promoter and
      enhancer subtypes, we show distinct enrichment of 5-hmC at enhancers marked with
      H3K4me1 and H3K27ac. These results suggest potential role(s) for 5-hmC in the
      regulation of specific promoters and enhancers. In addition, our results provide
      a detailed epigenomic map of 5-hmC from which to pursue future functional studies
      on the diverse regulatory roles associated with 5-hmC.

PMID- 21731510
TI  - Off-label.

PMID- 21731509
TI  - Local absence of secondary structure permits translation of mRNAs that lack
      ribosome-binding sites.
AB  - The initiation of translation is a fundamental and highly regulated process in
      gene expression. Translation initiation in prokaryotic systems usually requires
      interaction between the ribosome and an mRNA sequence upstream of the initiation
      codon, the so-called ribosome-binding site (Shine-Dalgarno sequence). However, a
      large number of genes do not possess Shine-Dalgarno sequences, and it is unknown
      how start codon recognition occurs in these mRNAs. We have performed genome-wide
      searches in various groups of prokaryotes in order to identify sequence elements
      and/or RNA secondary structural motifs that could mediate translation initiation
      in mRNAs lacking Shine-Dalgarno sequences. We find that mRNAs without a Shine
      Dalgarno sequence are generally less structured in their translation initiation
      region and show a minimum of mRNA folding at the start codon. Using reporter gene
      constructs in bacteria, we also provide experimental support for local RNA
      unfoldedness determining start codon recognition in Shine-Dalgarno--independent
      translation. Consistent with this, we show that AUG start codons reside in single
      stranded regions, whereas internal AUG codons are usually in structured regions
      of the mRNA. Taken together, our bioinformatics analyses and experimental data
      suggest that local absence of RNA secondary structure is necessary and sufficient
      to initiate Shine-Dalgarno--independent translation. Thus, our results provide a
      plausible mechanism for how the correct translation initiation site is recognized
      in the absence of a ribosome-binding site.

PMID- 21731511
TI  - Survivorship programs and care plans in practice: variations on a theme.
AB  - PURPOSE: THIS QUALITATIVE STUDY EXAMINED CANCER SURVIVORSHIP PROGRAMS AT FOUR
      HEALTH CARE ORGANIZATIONS IN LOS ANGELES COUNTY, CA: an academic medical center,
      a community hospital, a primary-care medical group, and a county hospital. The
      purpose was to describe the successful implementation of four distinctly
      different models of care, focusing on the creative development and use of the
      Institute of Medicine-recommended survivorship care plan (SCP) document in each
      setting. METHODS: In-depth semistructured interviews were done with survivorship
      teams to characterize each program and the development and use of the SCP at each
      institution. RESULTS: Each survivorship program has developed and implemented
      unique types of SCP documents. Specifically, a comprehensive SCP at the academic
      center, completed by the clinical team, which covers many facets of cancer
      survivorship; a patient-directed SCP at the community hospital, completed by the
      survivor with assistance of an oncology nurse and focused on treatment history
      and appropriate surveillance; an adapted ASCO SCP template at the primary-care
      medical group, completed via a partnership with contracted oncologists and
      focused on the treatment history, surveillance, and shared care between oncology
      and primary care; an adapted ASCO SCP template at the county hospital, completed
      by the survivorship nurse practitioner and focused on patient education, post
      treatment care, and institutional care coordination. CONCLUSION: The SCP document
      is a flexible tool that can be successfully adapted for use in extremely varied
      settings, from primary care to hospitals, to inform and educate patients and
      providers alike.

PMID- 21731512
TI  - Off-label use of rituximab in a multipayer insurance system.
AB  - PURPOSE: Off-label prescribing in oncology is common and unregulated. The aim of
      this study was to describe the off-label use of rituximab, a novel anti-CD20
      antibody, among patients from a large proprietary insurance database to
      understand how frequently and appropriately off-label prescribing occurs for this
      medication. PATIENTS AND METHODS: In this descriptive study, 11,232,642 patients
      were enrolled in the D2 Hawkeye commercial insurance database between 2001 and
      2007, and 2,782 patients received rituximab. The main outcome measures were
      quantity and type of off-label usage, and expenditures for off-label usage.
      RESULTS: Seven hundred five (25.3%) patients received rituximab for off-label
      indications, and of those, 332 (47.1%) received rituximab for uncertain or
      inadequate evidence-based diagnoses. Expenditures for off-label indications were
      17.1% of expenditures for rituximab usage. CONCLUSION: The frequent use of
      rituximab for off-label indications should lead to improved postapproval
      surveillance of biologics by the US Food and Drug Administration, so that use can
      be adequately studied. This will also facilitate improved regulatory mechanisms
      to ensure evidence-based use.

PMID- 21731513
TI  - Ontario protocol assessment level: clinical trial complexity rating tool for
      workload planning in oncology clinical trials.
AB  - PURPOSE: The Ontario Institute for Cancer Research supported the creation of a
      working group with the objective of developing a standard rating scale to
      evaluate clinical trial complexity and applying the scale to facilitate workload
      measurement for Ontario cancer research sites. METHODS: The lack of a mechanism
      to measure the workload involved in a clinical trials protocol was identified and
      confirmed by a literature review. To collect information on how Ontario sites
      were assessing workload, a survey was distributed and evaluated. As a result, the
      working group developed the Ontario Protocol Assessment Level (OPAL), a protocol
      complexity rating scale designed to capture the workload involved in a clinical
      trial. After a training workshop on the application, OPAL was evaluated by 17
      Ontario cancer centers to demonstrate its reliability and consistency during a 3
      month pilot study. RESULTS: Twenty-seven protocols were reviewed by multiple
      sites, and the majority of the sites reported OPAL score differences between 0
      and 1.5. CONCLUSION: OPAL provides clinical trials departments with an objective
      method of quantifying clinical trials activity on the basis of study protocol
      complexity. With consistent application of OPAL, sites can manage staffing
      objectively. The working group is continuing to monitor the application of OPAL
      in Ontario.

PMID- 21731514
TI  - Implementation in a large health system of a program to identify women at high
      risk for breast cancer.
AB  - PURPOSE: PATIENTS AT HIGH RISK FOR DEVELOPING BREAST CANCER CAN BE IDENTIFIED
      USING A VALIDATED PREDICTIVE TOOL: the Gail model. Patients thus identified can
      undergo careful breast cancer screening and be considered for preventive
      measures, such as chemoprevention with tamoxifen or raloxifene. An organized
      health system can create a screening and high-risk intervention program for
      breast cancer and potentially save lives and resources. Multiple components of
      the health system must work together in a multidisciplinary manner to
      successfully implement such a program. METHODS: Aurora Health Care is a large
      health system in Wisconsin. In 2007, a medical center within Aurora initiated a
      program to identify patients at high risk for developing breast cancer and
      intervene with screening and prevention. The program used the Gail model, which
      was administered to patients presenting for comprehensive physical examination at
      the women's center. RESULTS: During the first year, 5,718 Gail model scores were
      calculated, and 15.2% of patients were deemed high risk. Most were counseled by
      their primary care providers, and few underwent screening with magnetic resonance
      imaging, genetics consultation, or chemoprevention. Primary care providers
      expressed concerns regarding the accuracy of the Gail model, the additional time
      necessary for patient counseling, how few patients underwent chemoprevention, and
      perceived medicolegal risk. The program was altered to address these concerns.
      CONCLUSION: Success of a breast cancer risk and intervention program in a large
      health system is more likely if concerns of participating disciplines are
      acknowledged and addressed.

PMID- 21731515
TI  - Effects of early exercise on the development of lymphedema in patients with
      breast cancer treated with axillary lymph node dissection.
AB  - PURPOSE: Despite advances in the treatment of breast cancer, there is little
      research examining the prevention of lymphedema after breast and/or axillary
      surgery. Currently, there are no national guidelines for activity restrictions;
      however, many medical providers recommend restricting activity of the surgically
      affected arm, which can create quality-of-life issues as well as future medical
      issues for patients with breast cancer. METHODS: A literature review of several
      current research articles was performed. This report reviews four studies
      evaluating the effects of restricted activity versus progressive exercise and
      stretching activities on development of lymphedema. RESULTS: The results show
      that there is no difference in the risk of developing lymphedema when following
      activity guidelines. All four of the studies reviewed report results of either a
      decrease in the development of lymphedema or no increased risk of development of
      lymphedema when early exercise regimens are incorporated into postoperative care.
      CONCLUSION: The four research articles show promising results that support future
      change in practice guidelines. However, none of the studies report follow-up
      results beyond 2 years. Additionl evaluation to monitor long-term effects is
      warranted.

PMID- 21731516
TI  - Physician survey of the effect of the 21-gene recurrence score assay results on
      treatment recommendations for patients with lymph node-positive, estrogen
      receptor-positive breast cancer.
AB  - PURPOSE: To survey the effect of the 21-gene recurrence score (RS) assay results
      on adjuvant treatment recommendations for patients with lymph node-positive (N+),
      estrogen receptor-positive (ER+) breast cancer. METHODS: Medical oncologists who
      ordered the 21-gene RS assay were invited to complete a survey regarding their
      most recent patient with N+/ER+ breast cancer. We obtained responses from 160
      (16%) of the 1,017 medical oncologists. RESULTS: Most of the respondents were in
      community (71%) versus academic (25%) settings and had practiced for a median of
      11 years. T1, T2, or T3 disease was reported in 62%, 35%, and 3% of patients,
      respectively. One, two, three, or >= 4 nodes were reported in 69%, 18%, 6%, and
      3% of patients, respectively. Eighty-six percent of the oncologists made
      treatment recommendations before obtaining the RS; 51% changed their
      recommendations after receiving the RS. In 33%, treatment intensity decreased
      from chemotherapy plus hormonal therapy to hormonal therapy alone. In 9%,
      treatment intensity increased from hormonal therapy alone to chemotherapy plus
      hormonal therapy. In 8%, treatment recommendations changed in a way that did not
      fit the definition of either increased or decreased intensity. CONCLUSION: In
      this survey of physician practice, the RS result was used to guide adjuvant
      treatment decision making in N+/ER+ breast cancer more often in patients with
      tumors less than 5 cm in size and one to three positive lymph nodes than in
      patients with larger tumors and four or more positive nodes and yielded an
      overall reduction in recommendations for chemotherapy.

PMID- 21731517
TI  - A copay foundation assistance support program for patients receiving intravenous
      cancer therapy.
AB  - PURPOSE: With the advent of newer cancer therapies (eg, biologic and cytotoxic),
      treatment is becoming increasingly expensive for patients with cancer. Patients
      enrolled in Medicare and commercial insurance plans often have large copay
      requirements with each treatment cycle. Often, these patients undergo significant
      financial hardship, and some patients decline treatment. We have developed a
      support program that works closely with all copay assistance foundations to
      secure financial assistance to facilitate appropriate treatment. METHODS: In
      September, 2008 we initiated a coordinated program with various copay assistance
      foundations, including Healthwell, Cancer Care, Patient Access, Chronic Disease
      Fund, Beckstrand Cancer, Lilly Cares and the Leukemia and Lymphoma Society.
      Patients requesting assistance with chemotherapy copay were enrolled in this
      program. Information about income level, chemotherapy regimens, and associated
      copay was given to these foundations, who then determined the amount of monetary
      assistance. RESULTS: Since the initiation of this program, of 201 patients who
      began receiving chemotherapy, 25 (12.4%) requested assistance with this program
      for either intravenous or oral treatments. The current results of time delays for
      foundation decision, success rates and administrative costs to secure funding
      will be presented at the time of the poster presentation. CONCLUSION: Copay for
      chemotherapy drugs is a financial hardship for a significant number of patients.
      Coordinated resources must be provided and reimbursed to facilitate appropriate
      and sustainable cancer care. This program is a successful model for other centers
      to adopt.

PMID- 21731518
TI  - Physician and Practice Characteristics Influencing Tumor Board Attendance:
      Results From the Provider Survey of the Los Angeles Women's Health Study.
AB  - BACKGROUND: Coordination of care has grown in importance with the advent of new
      modalities of treatment that require specialized expertise. In cancer care,
      multidisciplinary approaches have shown improvements in quality of care. Tumor
      boards may provide a mechanism for improving coordination of care. We evaluated
      physician and practice characteristics that predict frequency of tumor board
      attendance. MATERIALS AND METHODS: This cross-sectional study used data obtained
      by surveying physicians of a population-based sample of women with incident
      breast cancer. Physicians were queried regarding tumor board attendance,
      specialty [medical oncologist (MO), radiation oncologist (RO), surgeon at a
      hospital with American College of Surgeons accreditation (ACOSSg) and surgeon
      without such affiliation (non-ACOSSg)], physician characteristics (gender,
      race/ethnicity, teaching involvement, patient volume, ownership interest) and
      practice setting (type, size, reimbursement method). Univariate, bivariate, and
      multivariate analyses were performed for the dependent variable characterizing
      provider report of frequency of tumor board attendance. RESULTS: Most surveyed
      physicians (83%) report attending tumor board weekly (58%) or monthly (25%).
      Specialty and higher patient volumes are significant predictors of more frequent
      attendance. Compared with the most prevalent specialty category (low-volume
      ACOSSgs), high-volume MOs attend more frequently (P = .01) and low volume non
      ACOSSgs attend less frequently (P = .00). CONCLUSIONS: Tumor board provides a
      structure for engaging providers in discussion of cancer cases that is designed
      to enhance quality of care. Tumor board agendas and formalized institution-wide
      policies could be designed to engage low-frequency attendees as a means to
      improve quality measures, promote multidisciplinary care, and potentially improve
      health outcomes.

PMID- 21731519
TI  - Tumor registry versus physician medical record review: a direct comparison of
      patients with pancreatic neuroendocrine tumors.
AB  - PURPOSE: Tumor registry (TR) data are becoming more prominently cited in research
      through increased use of the National Cancer Database. We aimed to establish the
      accuracy of TR data by comparing them with physician medical record review (MD
      review) using pancreatic neuroendocrine tumors (NETs) as an example. METHODS: For
      MD review, the health information system of an academic medical center was
      queried for patients with pancreatic International Classification of Diseases,
      ninth revision (ICD-9), codes from January 2000 to August 2008. A single
      physician investigator analyzed those medical records and identified patients
      with pancreatic NETs. For TR data, patients with pancreatic NETs were identified
      by two separate strategies. For the period of January 2000 to December 2006,
      patients were identified through manual review of pathology reports, admission
      and discharge sheets, and clinic visit logs. For January 2007 to August 2008,
      patients were identified using an automated case-finding program. RESULTS: In MD
      review, 1,192 patients with pancreatic ICD-9 codes were identified, 34 of whom
      were found to have pancreatic NETs. The TR indicated 15 patients with pancreatic
      NETs, four of whom were not identified during MD review. Of the total 38 patients
      identified by either strategy, pancreatic NET identification rate of the TR was
      39.5% compared with 89.5% in MD review. CONCLUSION: Academic TR analysis
      indicates a substantial proportion of patients with pancreatic NETs are not
      identified when compared with MD review. Most instances of patients going
      unidentified are the result of registry time lag and case-finding methodologies;
      specifically, physicians may define tumors with malignant potential differently.
      This may be applicable to other individual tumor registries as well as aggregate
      registry-based national studies.

PMID- 21731520
TI  - American society of clinical oncology clinical practice guideline update:
      recommendations on the role of bone-modifying agents in metastatic breast cancer.
AB  - Journal of Clinical Oncology recently published ASCO's update to its guideline on
      the use of bone-modifying agents for patients with bone metastases, the scope of
      which was narrowed to the use of bone-modifying agents for patients with evidence
      of bone metastases.

PMID- 21731521
TI  - Commentary: role of bone-modifying agents in metastatic breast cancer.

PMID- 21731522
TI  - Clinical investigator responsibilities.
AB  - When conducting a clinical trial, it is important that clinical investigators
      successfully meet all research expectations, including regulatory requirements
      and the Guidelines for Good Clinical Practice.

PMID- 21731523
TI  - Performance appraisal: a tool for practice improvement.
AB  - Yours may be among the many oncology practices without an appropriate performance
      review system in place. Lack of an effective evaluation system increases the risk
      of inefficiency, poor office morale, and high turnover rates.

PMID- 21731525
TI  - Data and knowledge.

PMID- 21731526
TI  - National oncology practice benchmark: an annual assessment of financial and
      operational parameters-2010 report on 2009 data.
AB  - Amid increases in costs and numbers of patients combined with decreasing or
      stagnant reimbursements from payers, many oncology practices are improving
      efficiency and decreasing costs. The National Oncology Practice Benchmark, a
      national survey of community practices, provides data to help practices improve
      and monitor progress as they adapt to the changing practice environment.

PMID- 21731527
TI  - Sleep and Obstructive Lung Diseases.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are common obstructive
      lung diseases affecting millions of people in the United States. As sleep
      disorders are also common, it is not surprising that many people with obstructive
      lung disease also suffer from sleep disorders. However, people with COPD and
      those with asthma have worse sleep quality and more sleep-related problems when
      compared to people with other chronic health problems. In addition, a pathologic
      relationship may exist between obstructive sleep apnea (OSA) and obstructive lung
      diseases. This review focuses on the epidemiology, pathogenesis, and clinical
      implications of sleep disturbances in asthma and COPD.

PMID- 21731528
TI  - Non-mammalian genetic model systems in sleep research.

PMID- 21731529
TI  - A targeted maximum likelihood estimator of a causal effect on a bounded
      continuous outcome.
AB  - Targeted maximum likelihood estimation of a parameter of a data generating
      distribution, known to be an element of a semi-parametric model, involves
      constructing a parametric model through an initial density estimator with
      parameter E representing an amount of fluctuation of the initial density
      estimator, where the score of this fluctuation model at E = 0 equals the
      efficient influence curve/canonical gradient. The latter constraint can be
      satisfied by many parametric fluctuation models since it represents only a local
      constraint of its behavior at zero fluctuation. However, it is very important
      that the fluctuations stay within the semi-parametric model for the observed data
      distribution, even if the parameter can be defined on fluctuations that fall
      outside the assumed observed data model. In particular, in the context of sparse
      data, by which we mean situations where the Fisher information is low, a
      violation of this property can heavily affect the performance of the estimator.
      This paper presents a fluctuation approach that guarantees the fluctuated density
      estimator remains inside the bounds of the data model. We demonstrate this in the
      context of estimation of a causal effect of a binary treatment on a continuous
      outcome that is bounded. It results in a targeted maximum likelihood estimator
      that inherently respects known bounds, and consequently is more robust in sparse
      data situations than the targeted MLE using a naive fluctuation model. When an
      estimation procedure incorporates weights, observations having large weights
      relative to the rest heavily influence the point estimate and inflate the
      variance. Truncating these weights is a common approach to reducing the variance,
      but it can also introduce bias into the estimate. We present an alternative
      targeted maximum likelihood estimation (TMLE) approach that dampens the effect of
      these heavily weighted observations. As a substitution estimator, TMLE respects
      the global constraints of the observed data model. For example, when outcomes are
      binary, a fluctuation of an initial density estimate on the logit scale
      constrains predicted probabilities to be between 0 and 1. This inherent
      enforcement of bounds has been extended to continuous outcomes. Simulation study
      results indicate that this approach is on a par with, and many times superior to,
      fluctuating on the linear scale, and in particular is more robust when there is
      sparsity in the data.

PMID- 21731530
TI  - An application of collaborative targeted maximum likelihood estimation in causal
      inference and genomics.
AB  - A concrete example of the collaborative double-robust targeted likelihood
      estimator (C-TMLE) introduced in a companion article in this issue is presented,
      and applied to the estimation of causal effects and variable importance
      parameters in genomic data. The focus is on non-parametric estimation in a point
      treatment data structure. Simulations illustrate the performance of C-TMLE
      relative to current competitors such as the augmented inverse probability of
      treatment weighted estimator that relies on an external non-collaborative
      estimator of the treatment mechanism, and inefficient estimation procedures
      including propensity score matching and standard inverse probability of treatment
      weighting. C-TMLE is also applied to the estimation of the covariate-adjusted
      marginal effect of individual HIV mutations on resistance to the anti-retroviral
      drug lopinavir. The influence curve of the C-TMLE is used to establish
      asymptotically valid statistical inference. The list of mutations found to have a
      statistically significant association with resistance is in excellent agreement
      with mutation scores provided by the Stanford HIVdb mutation scores database.

PMID- 21731531
TI  - Targeted maximum likelihood based causal inference: Part II.
AB  - In this article, we provide a template for the practical implementation of the
      targeted maximum likelihood estimator for analyzing causal effects of multiple
      time point interventions, for which the methodology was developed and presented
      in Part I. In addition, the application of this template is demonstrated in two
      important estimation problems: estimation of the effect of individualized
      treatment rules based on marginal structural models for treatment rules, and the
      effect of a baseline treatment on survival in a randomized clinical trial in
      which the time till event is subject to right censoring.

PMID- 21731532
TI  - Targeted maximum likelihood estimation of the parameter of a marginal structural
      model.
AB  - Targeted maximum likelihood estimation is a versatile tool for estimating
      parameters in semiparametric and nonparametric models. We work through an example
      applying targeted maximum likelihood methodology to estimate the parameter of a
      marginal structural model. In the case we consider, we show how this can be
      easily done by clever use of standard statistical software. We point out
      differences between targeted maximum likelihood estimation and other approaches
      (including estimating function based methods). The application we consider is to
      estimate the effect of adherence to antiretroviral medications on virologic
      failure in HIV positive individuals.

PMID- 21731533
TI  - Practical Risk Assessment and Management Issues Arising were we to Adopt Low-Dose
      Linearity for all Endpoints.
AB  - The 2009 National Research Council report, Science and Decisions, proposes
      harmonizing dose-response approaches for cancer and non-cancer endpoints, and for
      non-cancer quantitative risk assessment, this would usually take the form of a
      low-dose linear no-threshold dose-response curve. The soundness of this
      recommendation has been questioned, but I focus on its consequences if adopted,
      many of them apparently unintended. If most endpoints for most agents are assumed
      to have non-zero low-dose risks, then the critical-effect concept, choosing the
      one endpoint on which to calculate acceptable doses, loses its basis. All
      regulatory decisions, since they entail substituting some exposures (and their
      attendant risks) for others, become risk-risk trade-off decisions, and equity
      questions are raised since risk transfer is inevitably involved. A valid basis
      for estimating low-dose linear components is not evident, and upper-bound
      approaches fail to be reliably public health-protective owing to the risk trade
      off decisions that need to be faced.

PMID- 21731534
TI  - Hormesis in Regulatory risk assessment - Science and Science Policy.
AB  - This brief commentary will argue that whether hormesis is considered in
      regulatory risk assessment is a matter less of science than of science policy. I
      will first discuss the distinction between science and science policy and their
      roles in regulatory risk assessment. Then I will focus on factors that influence
      science policy, especially as it relates to the conduct of risk assessments to
      inform regulatory decisions, with a focus on the U.S. Environmental Protection
      Agency (EPA). The key questions will then be how does hormesis interact with
      current concepts of science and science policy for risk assessment? Finally, I
      look ahead to factors that may increase, or decrease, the likelihood of hormesis
      being incorporated into regulatory risk assessment.

PMID- 21731535
TI  - Methamphetamine preconditioning causes differential changes in striatal
      transcriptional responses to large doses of the drug.
AB  - Methamphetamine (METH) is a toxic drug of abuse, which can cause significant
      decreases in the levels of monoamines in various brain regions. However, animals
      treated with progressively increasing doses of METH over several weeks are
      protected against the toxic effects of the drug. In the present study, we tested
      the possibility that this pattern of METH injections might be associated with
      transcriptional changes in the rat striatum, an area of the brain which is known
      to be very sensitive to METH toxicity and which is protected by METH
      preconditioning. We found that the presence and absence of preconditioning
      followed by injection of large doses of METH caused differential expression in
      different sets of striatal genes. Quantitative PCR confirmed METH-induced changes
      in some genes of interest. These include small heat shock 27 kD proteins 1 and 2
      (HspB1 and HspB2), brain derived neurotrophic factor (BDNF), and heme oxygenase-1
      (Hmox-1). Our observations are consistent with previous studies which have
      reported that ischemic or pharmacological preconditioning can cause reprogramming
      of gene expression after lethal ischemic insults. These studies add to the
      growing literature on the effects of preconditioning on the brain transcriptome.

PMID- 21731536
TI  - Generic Hockey-Stick Model for Estimating Benchmark Dose and Potency: Performance
      Relative to BMDS and Application to Anthraquinone.
AB  - Benchmark Dose Model software (BMDS), developed by the U.S. Environmental
      Protection Agency, involves a growing suite of models and decision rules now
      widely applied to assess noncancer and cancer risk, yet its statistical
      performance has never been examined systematically. As typically applied, BMDS
      also ignores the possibility of reduced risk at low doses ("hormesis"). A
      simpler, proposed Generic Hockey-Stick (GHS) model also estimates benchmark dose
      and potency, and additionally characterizes and tests objectively for hormetic
      trend. Using 100 simulated dichotomous-data sets (5 dose groups, 50
      animals/group), sampled from each of seven risk functions, GHS estimators
      performed about as well or better than BMDS estimators, and a surprising
      observation was that BMDS mis-specified all of six non-hormetic sampled risk
      functions most or all of the time. When applied to data on rodent tumors induced
      by the genotoxic chemical carcinogen anthraquinone (AQ), the GHS model yielded
      significantly negative estimates of net potency exhibited by the combined rodent
      data, suggesting that-consistent with the anti-leukemogenic properties of AQ and
      structurally similar quinones-environmental AQ exposures do not likely increase
      net cancer risk. In addition to its simplicity and flexibility, the GHS approach
      offers a unified, consistent approach to quantifying environmental chemical risk.

PMID- 21731537
TI  - Postconditioning hormesis put in perspective: an overview of experimental and
      clinical studies.
AB  - A beneficial effect of applying mild stress to cells or organisms, that were
      initially exposed to a high dose of stress, has been referred to as
      'postconditioning hormesis'. The initial high dose of stress activates intrinsic
      self-recovery mechanisms. Modulation of these endogenous adaptation strategies by
      administration of a subsequent low dose of stress can confer effects that are
      beneficial to the biological system. Owing to its potentially therapeutic
      applications, postconditioning hormesis is subject to research in various
      scientific disciplines. This paper presents an overview of the dynamics of
      postconditioning hormesis and illustrates this phenomenon with a number of
      examples in experimental and clinical research.

PMID- 21731538
TI  - Radiation induced bystander effects in mice given low doses of radiation in vivo.
AB  - The 'bystander effect' phenomenon has challenged the traditional framework for
      assessing radiation damage by showing radiation induced changes in cells which
      have not been directly targeted, but are neighbors to or receive medium from
      directly hit cells. Our group performed a range of single and serial low dose
      irradiations on two genetically distinct strains of mice. Bladder explants
      established from these mice were incubated in culture medium, which was used to
      measure death responses in a keratinocyte reporter system. The study revealed
      that the medium harvested from bladder tissues' (ITCM) from acutely irradiated
      C57BL6 but not Balb/c mice, was able to induce clonogenic death. Administration
      of a priming dose(s) before a challenge dose to both C57BL6 and Balb/c mice
      stimulated reporter cell survival irrespective of the time interval between
      dose(s) delivery. When ITCM corresponding to both strains of mice was measured
      for its calcium mobilization inducing ability, results showed an elevation in
      intracellular calcium levels that was strain dependent. This indicates that
      genotype determined the type of bystander signal/response that was produced after
      exposure to low and acute doses of radiation. However, serial exposure conditions
      modified bystander signal production to induce similar effects that were
      characterized by excessive growth.

PMID- 21731539
TI  - Human lung cancer risks from radon - part I - influence from bystander effects -
      a microdose analysis.
AB  - Since the publication of the BEIR VI report in 1999 on health risks from radon, a
      significant amount of new data has been published showing various mechanisms that
      may affect the ultimate assessment of radon as a carcinogen, at low domestic and
      workplace radon levels, in particular the Bystander Effect (BE) and the Adaptive
      Response radio-protection (AR). We analyzed the microbeam and broadbeam alpha
      particle data of Miller et al. (1995, 1999), Zhou et al. (2001, 2003, 2004),
      Nagasawa and Little (1999, 2002), Hei et al. (1999), Sawant et al. (2001a) and
      found that the shape of the cellular response to alphas is relatively independent
      of cell species and LET of the alphas. The same alpha particle traversal dose
      response behavior should be true for human lung tissue exposure to radon progeny
      alpha particles. In the Bystander Damage Region of the alpha particle response,
      there is a variation of RBE from about 10 to 35. There is a transition region
      between the Bystander Damage Region and Direct Damage Region of between one and
      two microdose alpha particle traversals indicating that perhaps two alpha
      particle "hits" are necessary to produce the direct damage. Extrapolation of
      underground miners lung cancer risks to human risks at domestic and workplace
      levels may not be valid.

PMID- 21731540
TI  - Deadly radon in montana? A brief note.

PMID- 21731541
TI  - A Response to: Deadly Radon in Montana?

PMID- 21731542
TI  - Deadly radon in montana? A rebuttal to dr. Larsson.

PMID- 21731543
TI  - Novel Sample Preparation for Mass Spectral Analysis of Complex Biological
      Samples.
AB  - The ability to combine a selective capture strategy with on chip MALDI-TOF
      analysis allows for rapid, sensitive analysis of a variety of different analytes.
      In this overview a series of applications of capture enhanced laser desorption
      ionization time of flight (CELDI-TOF) mass spectrometry are described. The key
      feature of the assay is an off-chip capture step that utilizes high affinity
      bacterial binding proteins to capture a selected ligand. This allows large
      volumes of sample to be used and provides for a concentration step prior to
      transfer to a gold chip for traditional mass spectral analysis. The approach can
      also be adapted to utilize specific antibody as the basis of the capture step.
      The direct and indirect CELDI-TOF assays are rapid, reproducible and can be a
      valuable proteomic tool for analysis of low abundance molecules present in
      complex mixtures like blood plasma.

PMID- 21731544
TI  - Marine biocatalysts: enzymatic features and applications.
AB  - In several recent reports related to biocatalysis the enormous pool of
      biodiversity found in marine ecosystems is considered a profitable natural
      reservoir for acquiring an inventory of useful biocatalysts. These enzymes are
      characterized by well-known habitat-related features such as salt tolerance,
      hyperthermostability, barophilicity and cold adaptivity. In addition, their novel
      chemical and stereochemical characteristics increase the interest of biocatalysis
      practitioners both in academia and research industry. In this review, starting
      from the analysis of these featuring habitat-related properties, important
      examples of marine enzymes in biocatalysis will be reported. Completion of this
      report is devoted to the analysis of novel chemical and stereochemical
      biodiversity offered by marine biocatalysts with particular emphasis on current
      or potential applications of these enzymes in chemical and pharmaceutical fields.
      The analysis of literature cited here and the many published patent applications
      concerning the use of marine enzymes supports the view that these biocatalysts
      are just waiting to be discovered, reflecting the importance of the marine
      environment. The potential of this habitat should be thoroughly explored and
      possibly the way to access useful biocatalysts should avoid destructive large
      scale collections of marine biomass for enzyme production. These two aspects are
      day by day increasing in interest and a future increase in the use of marine
      enzymes in biocatalysis should be expected.

PMID- 21731545
TI  - Quantification of dissolved and particulate polyunsaturated aldehydes in the
      Adriatic sea.
AB  - Polyunsaturated aldehydes (PUA) are supposed to play critical roles in chemically
      mediated plankton interactions. Laboratory studies suggest that they act as
      mediators of chemical defense and chemical communication. PUA are oxylipins
      containing an alpha,beta,gamma,delta-unsaturated aldehyde structure element and
      are mainly found in diatoms. We present here a detailed surface mapping of PUA
      during a spring bloom of the diatom Skeletonema marinoi in the Adriatic Sea. We
      monitored dissolved PUA, as well as particulate PUA, which are produced by
      phytoplankton after cell disintegration. Our survey revealed a patchy
      distribution of PUA and shows that at most stations S. marinoi is the major
      contributor to the overall PUA. Our data also suggest that lysis of a diatom
      bloom can contribute significantly to the dissolved PUA concentrations and that
      other producers, which are smaller in cell size compared to diatoms, have to be
      taken into account as well if the total PUA content of marine samples is
      considered. The analyses of samples collected in deeper water suggests that
      diatom contribution to PUA decreases with depth, while smaller-sized unidentified
      organisms take place as dominant contributors to the PUA concentrations.

PMID- 21731546
TI  - Statistical research on marine natural products based on data obtained between
      1985 and 2008.
AB  - Since the 1960s, more than 20,000 compounds were discovered from marine
      organisms. In this paper we performed a quantitative analysis for the novel
      marine natural products reported between 1985 and 2008. The data was extracted
      mainly from the reviews of Faulkner and Blunt [1-26]. The organisms producing
      these marine natural products are divided into three major biological classes:
      marine microorganisms (including phytoplankton), marine algae and marine
      invertebrate. The marine natural products are divided into seven classes based on
      their chemical structure: terpenoids, steroids (including steroidal saponins),
      alkaloids, ethers (including ketals), phenols (including quinones),
      strigolactones, and peptides. The distribution and the temporal trend of these
      classes (biological classes and chemical structure classes) were investigated. We
      hope this article provides a comprehensive perspective on the research of marine
      natural products.

PMID- 21731547
TI  - The acute toxicity and hematological characterization of the effects of tentacle
      only extract from the jellyfish Cyanea capillata.
AB  - To investigate the hematologic changes and the activities of jellyfish venoms
      other than hemolytic and cardiovascular toxicities, the acute toxicity of
      tentacle-only extract (TOE) from the jellyfish Cyanea capillata was observed in
      mice, and hematological indexes were examined in rats. The median lethal dose
      (LD(50)) of TOE was 4.25 mg/kg, and the acute toxicity involved both heart- and
      nervous system-related symptoms. Arterial blood gas indexes, including pH,
      PCO(2), HCO(3) (-), HCO(3)std, TCO(2), BEecf and BE (B), decreased significantly.
      PO(2) showed a slight increase, while SO(2)c (%) had no change at any time. Na(+)
      and Ca(2+) decreased, but K(+) increased. Biochemical indexes, including LDH, CK,
      CK-MB, ALT, AST and sCr, significantly increased. Other biochemical indexes,
      including BUN and hemodiastase, remained normal. Lactic acid significantly
      increased, while glucose, Hct% and THbc showed slight temporary increases and
      then returned to normal. These results on the acute toxicity and hematological
      changes should improve our understanding of the in vivo pathophysiological
      effects of TOE from C. capillata and indicate that it may also have
      neurotoxicity, liver toxicity and muscular toxicity in addition to hemolytic and
      cardiovascular toxicities, but no kidney or pancreatic toxicity.

PMID- 21731548
TI  - Effects of high salt stress on secondary metabolite production in the marine
      derived fungus Spicaria elegans.
AB  - To obtain structurally novel and bioactive natural compounds from marine-derived
      microorganisms, the effect of high salt stress on secondary metabolite production
      in the marine-derived fungal strain, Spicaria elegans KLA-03, was investigated.
      The organism, which was isolated from marine sediment, produced different
      secondary metabolites when cultured in 3% and 10% saline conditions. Four
      characteristic metabolites, only produced in the 10% salinity culture, were
      isolated, and their structures were identified as (2E,2'Z)-3,3'-(6,6'
      dihydroxybiphenyl-3,3'-diyl)diacrylic acid (1), aspulvinone E (2), aspochalasin E
      (3) and trichodermamide B (6), according to their 1D and 2D NMR spectra. Compound
      1 is a new compound. High salt stress may therefore be a promising means to
      induce the production of new and chlorinated compounds in halotolerant fungi.
      Compound 1 showed moderate antibacterial activity against Pseudomonas aeruginosa
      and Escherichia coli with minimum inhibitory concentration (MIC) values of 0.038
      and 0.767 mM, respectively.

PMID- 21731549
TI  - First evidence of palytoxin and 42-hydroxy-palytoxin in the marine cyanobacterium
      Trichodesmium.
AB  - Marine pelagic diazotrophic cyanobacteria of the genus Trichodesmium
      (Oscillatoriales) are widespread throughout the tropics and subtropics, and are
      particularly common in the waters of New Caledonia. Blooms of Trichodesmium are
      suspected to be a potential source of toxins in the ciguatera food chain and were
      previously reported to contain several types of paralyzing toxins. The toxicity
      of water-soluble extracts of Trichodesmium spp. were analyzed by mouse bioassay
      and Neuroblastoma assay and their toxic compounds characterized using liquid
      chromatography coupled with tandem mass spectrometry techniques. Here, we report
      the first identification of palytoxin and one of its derivatives, 42-hydroxy
      palytoxin, in field samples of Trichodesmium collected in the New Caledonian
      lagoon. The possible role played by Trichodesmium blooms in the development of
      clupeotoxism, this human intoxication following the ingestion of plankton-eating
      fish and classically associated with Ostreopsis blooms, is also discussed.

PMID- 21731550
TI  - Phylogenetic identification of fungi isolated from the marine sponge Tethya
      aurantium and identification of their secondary metabolites.
AB  - Fungi associated with the marine sponge Tethya aurantium were isolated and
      identified by morphological criteria and phylogenetic analyses based on internal
      transcribed spacer (ITS) regions. They were evaluated with regard to their
      secondary metabolite profiles. Among the 81 isolates which were characterized,
      members of 21 genera were identified. Some genera like Acremonium, Aspergillus,
      Fusarium, Penicillium, Phoma, and Trichoderma are quite common, but we also
      isolated strains belonging to genera like Botryosphaeria, Epicoccum,
      Parasphaeosphaeria, and Tritirachium which have rarely been reported from
      sponges. Members affiliated to the genera Bartalinia and Volutella as well as to
      a presumably new Phoma species were first isolated from a sponge in this study.
      On the basis of their classification, strains were selected for analysis of their
      ability to produce natural products. In addition to a number of known compounds,
      several new natural products were identified. The scopularides and sorbifuranones
      have been described elsewhere. We have isolated four additional substances which
      have not been described so far. The new metabolite cillifuranone (1) was isolated
      from Penicillium chrysogenum strain LF066. The structure of cillifuranone (1) was
      elucidated based on 1D and 2D NMR analysis and turned out to be a previously
      postulated intermediate in sorbifuranone biosynthesis. Only minor antibiotic
      bioactivities of this compound were found so far.

PMID- 21731551
TI  - Coccolithophores: functional biodiversity, enzymes and bioprospecting.
AB  - Emiliania huxleyi is a single celled, marine phytoplankton with global
      distribution. As a key species for global biogeochemical cycling, a variety of
      strains have been amassed in various culture collections. Using a library
      consisting of 52 strains of E. huxleyi and an 'in house' enzyme screening
      program, we have assessed the functional biodiversity within this species of
      fundamental importance to global biogeochemical cycling, whilst at the same time
      determining their potential for exploitation in biocatalytic applications. Here,
      we describe the screening of E. huxleyi strains, as well as a coccolithovirus
      infected strain, for commercially relevant biocatalytic enzymes such as
      acid/alkali phosphodiesterase, acid/alkali phosphomonoesterase, EC1.1.1-type
      dehydrogenase, EC1.3.1-type dehydrogenase and carboxylesterase.

PMID- 21731552
TI  - Heterofucan from Sargassum filipendula induces apoptosis in HeLa cells.
AB  - Fucan is a term used to denominate a family of sulfated polysaccharides rich in
      sulfated l-fucose. Heterofucan SF-1.5v was extracted from the brown seaweed
      Sargassum filipendula by proteolytic digestion followed by sequential acetone
      precipitation. This fucan showed antiproliferative activity on Hela cells and
      induced apoptosis. However, SF-1.5v was not able to activate caspases. Moreover,
      SF-1.5v induced glycogen synthase kinase (GSK) activation, but this protein is
      not involved in the heterofucan SF-1.5v induced apoptosis mechanism. In addition,
      ERK, p38, p53, pAKT and NFkappaB were not affected by the presence of SF-1.5v. We
      determined that SF-1.5v induces apoptosis in HeLa mainly by mitochondrial release
      of apoptosis-inducing factor (AIF) into cytosol. In addition, SF-1.5v decreases
      the expression of anti-apoptotic protein Bcl-2 and increased expression of
      apoptogenic protein Bax. These results are significant in that they provide a
      mechanistic framework for further exploring the use of SF-1.5v as a novel
      chemotherapeutics against human cervical cancer.

PMID- 21731553
TI  - Biodegradable and biocompatible biomaterial, polyhydroxybutyrate, produced by an
      indigenous Vibrio sp. BM-1 isolated from marine environment.
AB  - Polyhydroxybutyrate (PHB) is one of the polyhydroxyalkanoates (PHAs) which has
      biodegradable and biocompatible properties. They are adopted in the biomedical
      field, in, for example, medical implants and drug delivery carriers. This study
      seeks to promote the production of PHB by Vibrio sp. BM-1, isolated from a marine
      environment by improving constituents of medium and implementing an appropriate
      fermentation strategy. This study successfully developed a glycerol-yeast extract
      tryptone (GYT) medium that can facilitate the growth of Vibrio sp. BM-1 and lead
      to the production of 1.4 g/L PHB at 20 h cultivation. This study also shows that
      1.57 g/L PHB concentration and 16% PHB content were achieved, respectively, when
      Vibrio sp. BM-1 was cultivated with MS-GYT medium (mineral salts-supplemented GYT
      medium) for 12 h. Both cell dry weight (CDW) and residual CDW remained constant
      at around 8.2 g/L and 8.0 g/L after the 12 h of cultivation, until the end of the
      experiment. However, both 16% of PHB content and 1.57 g/L of PHB production
      decreased rapidly to 3% and 0.25 g/L, respectively from 12 h of cultivation to 40
      h of cultivation. The results suggest that the secretion of PHB depolymerase that
      might be caused by the addition of mineral salts reduced PHB after 12 h of
      cultivation. However, work will be done to explain the effect of adding mineral
      salts on the production of PHB by Vibrio sp. BM-1 in the near future.

PMID- 21731554
TI  - Microalgae as sources of carotenoids.
AB  - Marine microalgae constitute a natural source of a variety of drugs for
      pharmaceutical, food and cosmetic applications-which encompass carotenoids, among
      others. A growing body of experimental evidence has confirmed that these
      compounds can play important roles in prevention (and even treatment) of human
      diseases and health conditions, e.g., cancer, cardiovascular problems,
      atherosclerosis, rheumatoid arthritis, muscular dystrophy, cataracts and some
      neurological disorders. The underlying features that may account for such
      favorable biological activities are their intrinsic antioxidant, anti
      inflammatory and antitumoral features. In this invited review, the most important
      issues regarding synthesis of carotenoids by microalgae are described and
      discussed-from both physiological and processing points of view. Current gaps of
      knowledge, as well as technological opportunities in the near future relating to
      this growing field of interest, are also put forward in a critical manner.

PMID- 21731555
TI  - Carbohydrase systems of Saccharophagus degradans degrading marine complex
      polysaccharides.
AB  - Saccharophagus degradans 2-40 is a gamma-subgroup proteobacterium capable of
      using many of the complex polysaccharides found in the marine environment for
      growth. To utilize these complex polysaccharides, this bacterium produces a
      plethora of carbohydrases dedicated to the processing of a carbohydrate class.
      Aiding in the identification of the contributing genes and enzymes is the known
      genome sequence for this bacterium. This review catalogs the genes and enzymes of
      the S. degradans genome that are likely to function in the systems for the
      utilization of agar, alginate, alpha- and beta-glucans, chitin, mannans, pectins,
      and xylans and discusses the cell biology and genetics of each system as it
      functions to transfer carbon back to the bacterium.

PMID- 21731556
TI  - Polymer networks produced by marine diatoms in the northern Adriatic sea.
AB  - Using high resolution molecular technique of atomic force microscopy, we address
      the extracellular polymer production of Adriatic diatom Cylindrotheca closterium
      analyzed at the single cell level and the supramolecular organization of gel
      phase isolated from the Northern Adriatic macroaggregates. Our results revealed
      that extracellular polysaccharides freshly produced by marine diatoms can self
      assemble directly to form gel network characteristics of the macroscopic gel
      phase in the natural aquatorium. Based on the experiments performed with isolated
      polysaccharide fractions of C. closterium and of macroaggregates gel phase, we
      demonstrated that the polysaccharide self-assembly into gel network can proceed
      independent of any bacterial mediation or interaction with inorganic particles.

PMID- 21731557
TI  - Bactericidal kinetics of marine-derived napyradiomycins against contemporary
      methicillin-resistant Staphylococcus aureus.
AB  - There is an urgent need for new antibiotics to treat hospital- and community
      associated methicillin-resistant Staphylococcus aureus (MRSA) infections.
      Previous work has indicated that both terrestrial and marine-derived members of
      the napyradiomycin class possess potential anti-staphylococcal activities. These
      compounds are unique meroterpenoids with unusual levels of halogenation. In this
      paper we report the evaluation of two previously described napyradiomycin
      derivatives, A80915A (1) and A80915B (2) produced by the marine-derived
      actinomycete, Streptomyces sp. strain CNQ-525, for their specific activities
      against contemporary and clinically relevant MRSA. Reported are studies of the in
      vitro kinetics of these chemical scaffolds in time-kill MRSA assays. Both
      napyradiomycin derivatives demonstrate potent and rapid bactericidal activity
      against contemporary MRSA strains. These data may help guide future development
      and design of analogs of the napyradiomycins that could potentially serve as
      useful anti-MRSA therapeutics.

PMID- 21731558
TI  - Why we should use animals to study economic decision making - a perspective.
AB  - Despite the rich tradition in psychology and biology, animals as research
      subjects have never gained a similar acceptance in microeconomics research. With
      this article, we counter this trend of negligence and try to convey the message
      that animal models are an indispensible complement to the literature on human
      economic decision making. This perspective review departs from a description of
      the similarities in economic and evolutionary theories of human and animal
      decision making, with particular emphasis on the optimality aspect that both
      classes of theories have in common. In a second part, we outline that actual,
      empirically observed decisions often do not conform to the normative ideals of
      economic and ecological models, and that many of the behavioral violations found
      in humans can also be found in animals. In a third part, we make a case that the
      sense or nonsense of the behavioral violations of optimality principles in humans
      can best be understood from an evolutionary perspective, thus requiring animal
      research. Finally, we conclude with a critical discussion of the parallels and
      inherent differences in human and animal research.

PMID- 21731559
TI  - Adenosine A(2A) Receptors and A(2A) Receptor Heteromers as Key Players in
      Striatal Function.
AB  - A very significant density of adenosine A(2A) receptors (A(2A)Rs) is present in
      the striatum, where they are preferentially localized postsynaptically in
      striatopallidal medium spiny neurons (MSNs). In this localization A(2A)Rs
      establish reciprocal antagonistic interactions with dopamine D(2) receptors
      (D(2)Rs). In one type of interaction, A(2A)R and D(2)R are forming heteromers
      and, by means of an allosteric interaction, A(2A)R counteracts D(2)R-mediated
      inhibitory modulation of the effects of NMDA receptor stimulation in the
      striatopallidal neuron. This interaction is probably mostly responsible for the
      locomotor depressant and activating effects of A(2A)R agonist and antagonists,
      respectively. The second type of interaction involves A(2A)R and D(2)R that do
      not form heteromers and takes place at the level of adenylyl cyclase (AC). Due to
      a strong tonic effect of endogenous dopamine on striatal D(2)R, this interaction
      keeps A(2A)R from signaling through AC. However, under conditions of dopamine
      depletion or with blockade of D(2)R, A(2A)R-mediated AC activation is unleashed
      with an increased gene expression and activity of the striatopallidal neuron and
      with a consequent motor depression. This interaction is probably the main
      mechanism responsible for the locomotor depression induced by D(2)R antagonists.
      Finally, striatal A(2A)Rs are also localized presynaptically, in cortico-striatal
      glutamatergic terminals that contact the striato-nigral MSN. These presynaptic
      A(2A)Rs heteromerize with A(1) receptors (A(1)Rs) and their activation
      facilitates glutamate release. These three different types of A(2A)Rs can be
      pharmacologically dissected by their ability to bind ligands with different
      affinity and can therefore provide selective targets for drug development in
      different basal ganglia disorders.

PMID- 21731560
TI  - The Effects of Suffering in Chronically Ill Older Adults on the Health and Well
      Being of Family Members Involved in Their Care: The Role of Emotion-Related
      Processes.
AB  - A large literature shows that caregivers of chronically ill older adults have a
      higher risk for impaired health and decreased longevity. In this paper we review
      research that addresses pathways through which family members experience negative
      health consequences from exposure to a partner's suffering. We first provide a
      conceptualization of suffering and describe how it can be measured, then review
      empirical evidence that exposure to suffering uniquely influences caregivers'
      health, and discuss individual differences in caregivers' emotional reactions to
      partners' suffering using three emotion theories (Gross' process model of emotion
      regulation, attachment theory, and a functionalist perspective on emotion).
      Finally, we discuss implications of the effects of suffering for the health and
      well-being of family caregivers.

PMID- 21731561
TI  - Heterotaxy syndrome.
AB  - Heterotaxy is defined as an abnormality where the internal thoraco-abdominal
      organs demonstrate abnormal arrangement across the left-right axis of the body.
      This broad term includes patients with a wide variety of very complex cardiac
      lesions. Patients with heterotaxy can be stratified into the subsets of asplenia
      syndrome and polysplenia syndrome, or the subsets of heterotaxy with isomerism of
      the right atrial appendages and heterotaxy with isomerism of the left atrial
      appendages. Treatment of patients with isomerism is determined by the nature and
      severity of the associated cardiac and extracardiac lesions. Most cardiac
      operations for patients with isomerism are palliative in nature, since normal
      anatomy is rarely achieved and mortality rates remain high for patients with
      heterotaxy syndrome. Patients with left isomerism in general have less severe
      cardiac malformations than those with right isomerism and, hence, more chance of
      biventricular repair. For almost all patients with right isomerism, and for many
      with left isomerism, biventricular repair will not be feasible, and all
      palliative protocols are then staging procedures prior to a Fontan-type repair.
      Recent advances in medical management, and improvements in surgical techniques
      have resulted in improved survival for these patients, and the surgical outcomes
      are comparable to those with Fontan circulation irrespective of the presence or
      absence of heterotaxy.

PMID- 21731562
TI  - Evolving coronary stents coated with new bioactive agents.

PMID- 21731563
TI  - The relationship between ambulatory arterial stiffness index and blood pressure
      variability in hypertensive patients.
AB  - BACKGROUND AND OBJECTIVES: Ambulatory arterial stiffness index (AASI) is well
      known as a predictor of cardiovascular mortality in hypertensive patients.
      Mathematically, AASI reflect the standard deviation (SD) of blood pressure (BP)
      variation. AASI is measured higher levels in non-dipper than dipper. Thus, AASI
      has a possibility of not only reflecting arterial stiffness but also BP
      variability and/or autonomic nervous dysfunction. SUBJECTS AND METHODS:
      Consecutive data from 418 untreated hypertensive patients were analyzed
      retrospectively. We examined the association between the 24-hour ambulatory BP
      monitoring (ABPM) parameters and AASI. RESULTS: AASI had a simple correlation
      with age (R=0.189, p<0.001), relative wall thickness (RWT) (R=0.115, p=0.019),
      left ventricular mass index (LVMI) (R=0.192, p<0.001), average systolic BP (SBP)
      (R=0.232, p<0.001), average pulse pressure (PP) (R=0.363, p<0.001), SD of
      diastolic BP (DBP) (R=-0.352, p<0.001), SD of PP (R=0.330, p<0.001), SD of heart
      rate (HR) (R=-0.268, p<0.001), and nocturnal dipping (R=-0.137, p=0.005). In
      multiple linear regression analysis model including clinical parameters and 24
      hour-ABPM parameters, independent predictors of AASI were SD of PP (beta=1.246,
      p<0.001), SD of DBP (beta=-1.067, p<0.001), SD of SBP (beta=-0.197, p<0.001), and
      non-dipper (beta=0.054, p=0.033). CONCLUSION: AASI is closely correlated with BP
      variability. The result of this study shows that AASI is not only a parameter for
      arterial stiffness, but also a parameter for BP variability.

PMID- 21731564
TI  - Effect of a dual drug-coated stent with abciximab and alpha-lipoic Acid in a
      porcine coronary restenosis model.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to examine the anti
      proliferative and anti-inflammatory effects of a stent coated with abciximab and
      alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model.
      MATERIALS AND METHODS: A total of 10 pigs were randomized into two groups (10
      pigs, 10 coronaries in each group) in which the coronary arteries were stented
      with a dual-coated stent and a bare metal stent (control) by randomization.
      Stents were deployed with oversizing (stent/artery ratio 1.3 : 1) in the porcine
      coronary arteries, and histopathology was assessed 28 days after stenting.
      RESULTS: There was no significant difference in the injury score between the two
      groups. In the neointima, the lymphohistiocyte count was significantly lower in
      dual-coat stent group compared with the control stent group (120+/-85 cells vs.
      159+/-80 cells, p=0.048). There was no significant difference in the fibrin score
      between the two groups (0.16+/-0.34 in the dual-coated stent group vs. 0.25+/
      0.48 in the control stent group, p=0.446). The neointima area was not
      significantly different between both groups (1.55+/-0.8 mm(2) in dual-coated
      stent group vs. 1.40+/-0.86 mm(2) in the control stent group, p=0.447).
      CONCLUSION: Although the dual-coated stent with abciximab and ALA showed no
      significant difference in inhibition of neointimal hyperplasia when compared with
      the bare metal stent, it was associated with a reduced inflammatory reaction when
      compared with the control stent in a porcine coronary restenosis model.

PMID- 21731565
TI  - Comparison of magnetic navigation system and conventional method in catheter
      ablation of atrial fibrillation: is magnetic navigation system is more effective
      and safer than conventional method?
AB  - BACKGROUND AND OBJECTIVES: Although there have been so many reports of catheter
      ablation of atrial fibrillation (AF) with magnetic navigation system (MNS), it is
      not necessarily obvious that MNS is more effective than conventional ablation. We
      performed AF ablation with MNS and compared the clinical outcomes and
      radiofrequency ablation parameters with those of conventional ablation. SUBJECTS
      AND METHODS: One hundred eleven consecutive patients (conventional group, n=70
      vs. MNS group, n=41) undergoing catheter ablation of AF were enrolled. We
      compared and analyzed the procedural parameters, namely fluoroscopic time,
      procedural time, acute procedural success and 3 months success rate of both
      groups. RESULTS: The MNS group was associated with slightly larger left atrial
      size (43.7+/-6.3 mm vs. 41.2+/-6.3 mm, p=0.04), significantly longer total
      procedure time (352+/-50 minutes vs. 283+/-75 minutes, p<0.0001), and shorter
      total fluoroscopic time (99+/-28 minutes vs. 238+/-45 minutes, p<0.0001) than the
      conventional group. The MNS and conventional group did not differ with respect to
      acute procedural success, AF recurrence, atrial flutter/atrial tachycardia
      recurrence, or total arrhythmia recurrence. While no complications were observed
      in the MNS group, eight cases of significant pericardial effusion occurred in the
      conventional group. CONCLUSION: The MNS system seems to be effective and safe in
      the catheter ablation of AF, particularly in the population of patients with
      persistent AF and slightly dilated left atria.

PMID- 21731566
TI  - Effects of ezetimibe added to ongoing statin therapy on C-reactive protein levels
      in hypercholesterolemic patients.
AB  - BACKGROUND AND OBJECTIVES: Ezetimibe alone does not decrease C-reactive protein
      (CRP) levels in hypercholesterolemic patients. However, several reports have
      suggested that ezetimibe might potentiate the effect of statin not only on
      cholesterol but also on CRP when administered together. We investigated the
      effect of ezetimibe on CRP levels in patients taking statins. SUBJECTS AND
      METHODS: Patients who had not achieved recommended low density lipoprotein
      cholesterol (LDL-C) goals with statin therapy were divided into two groups, the
      ezetimibe group (n=60) and the control group (n=60). A third group of
      hypercholesterolemic patients without statin therapy was treated with statin
      (n=59). Patients with CRP level 10 mg/L were excluded. Lipid and CRP levels were
      measured before therapy commenced, and after 2 months of therapy. RESULTS:
      Ezetimibe decreased cholesterol and LDL-C levels by 20.2% (p=0.000) and 28.1%
      (p=0.000) respectively. However, ezetimibe did not reduce CRP levels (from 0.83+/
      0.68 to 1.14+/-1.21 mg/dL, p=0.11). CRP levels remained unchanged in the control
      group (p=0.42). In contrast, statin lowered CRP levels (from 0.82+/-0.73 to
      0.65+/-0.57 mg/dL, p=0.008). In patients taking statins, changes in CRP levels
      were not associated with changes in LDL-C (r=-0.02, p=0.87), but with baseline
      CRP levels (r=-0.38, p=0.000). CONCLUSION: Ezetimibe failed to reduce CRP levels
      in hypercholesterolemic patients taking statins despite significant reduction of
      LDL-C. This finding suggests that the anti-inflammatory effect of statin may not
      be secondary to cholesterol reduction, but via other mechanisms.

PMID- 21731567
TI  - Knowledge of stroke and heart attack symptoms and risk factors among rural
      elderly people: a questionnaire survey.
AB  - BACKGROUND AND OBJECTIVES: To determine the level of knowledge of stroke and
      heart attack (HA) symptoms and risk factors of cardiovascular disease (CVD) in
      rural elderly people who are at risk for CVD. SUBJECTS AND METHODS: A total of
      444 adults over the age of 60 living in a rural province of Korea with at least
      one CVD risk factor participated in this survey. RESULTS: A total of 72.5% of the
      participants had hypertension and 28.4% had diabetes, whereas approximately 40%
      exhibited over two CVD risk factors. The mean knowledge scores for HA symptoms
      (4.3/9) were lower than scores for stroke symptoms (5.8/9), and the mean
      knowledge score for risk factors was 7.3/11. Stepwise multiple regression
      analyses showed that old age, low level of education, and low income level were
      the determining factors for low knowledge levels of stroke and HA symptoms as
      well as CVD risk factors. A low perceived risk of stroke or HAs also predicted a
      low knowledge of CVD risk factors. CONCLUSION: Community-wide public campaigns
      are needed, which are designed to help elderly people in rural areas with low
      education levels and socioeconomic status at risk for CVD to improve the
      awareness of stroke and HA.

PMID- 21731568
TI  - Determination of safe contrast media dosage to estimated glomerular filtration
      rate ratios to avoid contrast-induced nephropathy after elective percutaneous
      coronary intervention.
AB  - BACKGROUND AND OBJECTIVES: To avoid the risk of developing contrast-induced
      nephropathy (CIN), it has been suggested that patients be subjected to a minimal
      necessary dose of contrast medium (CM-dose). However, often it is not easy to
      determine such a dose. This study assessed the usefulness of the ratio of CM-dose
      to estimated glomerular filtration rate (eGFR) in predicting the risks of CIN and
      sought to determine the safe level of CM-dose/eGFR in patients undergoing non
      emergent percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We
      enrolled a total of 226 patients and calculated the ratio of CM-dose using grams
      of iodine (g-I) to eGFR, thus expressing it as g-I/eGFR. Among the CIN patients,
      those with ne-phropathy requiring dialysis (NRD) were also evaluated. RESULTS:
      Overall, there were 16 cases (7.1%) of CIN. On univariate and multivariate
      regression analysis, g-I/eGFR alone was found to be an independent predictor for
      CIN (hazard ratio=10.73, p<0.001). In an receiver operating characteristic
      analysis, fair discrimination for CIN was found at a g-I/eGFR level of 1.42 (C
      statics=0.867), and at this value, the sensitivity and specificity were 81.3% and
      80%, respectively. Of patients (n=51) with g-I/eGFR >=1.42, 23.6% (13/51) and
      7.8% (4/51) developed, while those with g-I/eGFR <1.42 (n=171) had a lower
      incidences of CIN (1.8%, 2/171, p<0.001) and NRD (0%, 0/171, p<0.001).
      CONCLUSION: It can be concluded that a g-I/eGFR <1.42 is a simple, useful
      indicator for determining the safe CM-dose based on the pre-PCI eGFR values.
      Furthermore, g-I/eGFR might have a close relationship with the development of NRD
      as well as CIN.

PMID- 21731569
TI  - Isolated double-chambered right ventricle in a young adult.
AB  - Double-chambered right ventricle (DCRV) is a rare congenital heart disorder in
      which the right ventricle is divided by an anomalous muscle bundle into a high
      pressure inlet portion and a low pressure outlet portion. We report a case of
      isolated DCRV without symptoms in adulthood, diagnosed through echocardiography,
      cardiac catheterization and cardiac magnetic resonance imaging.

PMID- 21731570
TI  - Progressive familial heart block type I in a korean patient.
AB  - A 29-year-old man was referred to the emergency department with a complaint of
      abdominal pain and dizziness. He had experienced two previous syncopal episodes.
      His family history revealed that his mother and his two uncles had received
      permanent pacemaker implantation. His initial heart rate was 49 beats per minute.
      The electrocardiography (ECG) showed atrial flutter and right bundle branch block
      (RBBB) with left anterior fascicular block (LAFB). On admission, 24-hour Holter
      showed ventricular pause up to 16 seconds during syncope. Radio frequency
      catheter ablation (RFCA) of atrial flutter was performed. The ECG revealed
      bifascicular block (RBBB and LAFB) and first-degree atrioventricular block. He
      received a permanent pacemaker implantation. His brother's and his sister's ECGs
      also showed trifascicular block and the pedigree showed autosomal dominant
      inheritance. This patient was diagnosed with a progressive familial heart block
      (PFHB) type I. This would be the first report of a PFHB type I case documented in
      Korea.

PMID- 21731571
TI  - Pneumopericardium as a complication of pericardiocentesis.
AB  - Pneumopericardium is a rare complication of pericardiocentesis, occurring either
      as a result of direct pleuro-pericardial communication or a leaky drainage
      system. Air-fluid level surrounding the heart shadow within the pericardium on a
      chest X-ray is an early observation at diagnosis. This clinical measurement and
      process is variable, depending on the hemodynamic status of the patient. The
      development of a cardiac tamponade is a serious complication, necessitating
      prompt recognition and treatment. We recently observed a case of
      pneumopericardium after a therapeutic pericardiocentesis in a 20-year-old man
      with tuberculous pericardial effusion.

PMID- 21731572
TI  - Transient right ventricular dysfunction after pericardiectomy in patients with
      constrictive pericarditis.
AB  - Pericardiectomy is the standard treatment in patients with chronic constrictive
      pericarditis who have persistent symptoms. However, myocardial atrophy with
      prolonged pericardial constriction and abrupt increase in venous return can lead
      to heart failure with volume overload after pericardial decompression, especially
      in the right ventricle (RV). We experienced a 44 year old male patient who
      developed transient RV failure after pericardiectomy for constrictive
      pericarditis. Echocardiography revealed a markedly dilated RV with decreased peak
      systolic velocity of the tricuspid annulus, suggesting severe RV dysfunction.
      After treatment with inotropics and diuretics, a follow-up echocardiography
      revealed an improved systolic function with decreased RV chamber size. This case
      demonstrates the importance of volume overload and RV dysfunction in patients
      with constrictive pericarditis undergoing pericardiectomy.

PMID- 21731573
TI  - Lactogens and estrogens in breast cancer chemoresistance.
AB  - Tumor resistance to chemotherapy in advanced breast cancer is a major impediment
      to treatment success. Resistance can be induced by the drugs themselves or result
      from the action of internal factors. The role of hormones in chemoresistance has
      received little attention. This article focuses on two classes of hormones:
      lactogens and estrogens. Lactogens include prolactin, growth hormone and
      placental lactogen, all of which can activate the prolactin receptor. Estrogens
      include endogenous steroids and nonsteroidal compounds from the environment
      termed endocrine disruptors, all of which can activate 'classical' estrogen
      receptors (ERalpha and ERbeta), as well as other types of receptors. Both
      lactogens and estrogens antagonize cytotoxicity of multiple chemotherapeutic
      agents through complementary mechanisms. The implications of chemoresistance by
      these hormones to patients with breast cancer, and the potential benefits of
      developing combinatorial anti-lactogen/anti-estrogen treatment regimens, are
      discussed.

PMID- 21731574
TI  - Solubility Limits of Cholesterol, Lanosterol, Ergosterol, Stigmasterol, and beta
      Sitosterol in Electroformed Lipid Vesicles.
AB  - Here we use nuclear magnetic resonance to measure the solubility limit of several
      biologically relevant sterols in electroformed giant unilamellar vesicle
      membranes containing phosphatidylcholine (PC) lipids in ratios of 1:1:X
      DOPC:DPPC:sterol. We find solubility limits of cholesterol, lanosterol,
      ergosterol, stigmasterol, and beta-sitosterol to be 65-70%, ~35%, 30-35%, 20-25%,
      and ~40%, respectively. The low solubilities of stigmasterol and beta-sitosterol,
      which differ from cholesterol only in their alkyl tails, show that subtle
      differences in tail structure can strongly affect sterol solubility. Below the
      solubility limits, the fraction of sterol to PC-lipid in electroformed vesicles
      linearly reflects the fraction in the original stock solutions used in the
      electroformation process.

PMID- 21731575
TI  - Green Tea Polyphenols in drug discovery - a success or failure?
AB  - Green tea is made from unfermented dried leaves from Camellia sinensis and has
      been consumed by humans for thousands of years. For nearly as long, it has been
      used as a folk remedy for a wide array of diseases. More recently, a large number
      of in-vitro and in-vivo scientific studies have supported this ancient contention
      that the polyphenols from green tea can provide a number of health benefits.
      Since these compounds are clearly safe for human consumption and ubiquitous in
      the food supply, they are highly attractive as lead compounds for drug discovery
      programs. However, as drugs, they are far from optimum. They are relatively
      unstable, poorly absorbed, and readily undergo a number of metabolic
      transformations by intestinal microbiota and human enzymes. Further, since these
      compounds target a wide array of biological systems, in-vivo testing is rather
      difficult since effects on alternative pathways need to be carefully eliminated.
      The purpose of this review is to discuss some of the challenges and benefits of
      pursuing this family of compounds for drug discovery.

PMID- 21731576
TI  - Homeostatic bioenergetic network regulation - a novel concept to avoid
      pharmacoresistance in epilepsy.
AB  - INTRODUCTION: Despite epilepsy being one of the most prevalent neurological
      disorders, one third of all patients with epilepsy cannot adequately be treated
      with available antiepileptic drugs. One of the significant causes for the failure
      of conventional pharmacotherapeutic treatment is the development of
      pharmacoresistance in many forms of epilepsy. The problem of pharmacoresistance
      has called for the development of new conceptual strategies that improve future
      drug development efforts.  AREAS COVERED: A thorough review of the recent
      literature on pharmacoresistance in epilepsy was completed and select examples
      were chosen to highlight the mechanisms of pharmacoresistance in epilepsy and to
      demonstrate how those mechanistic findings might lead to improved treatment of
      pharmacoresistant epilepsy. The reader will gain a thorough understanding of
      pharmacoresistance in epilepsy and an appreciation of the limitations of
      conventional drug development strategies.  EXPERT OPINION: Conventional drug
      development efforts aim to achieve specificity of symptom control by enhancing
      the selectivity of drugs acting on specific downstream targets; this conceptual
      strategy bears the undue risk of development of pharmacoresistance. Modulation of
      homeostatic bioenergetic network regulation is a novel conceptual strategy to
      affect whole neuronal networks synergistically by mobilizing multiple endogenous
      biochemical and receptor-dependent molecular pathways. In our expert opinion we
      conclude that homeostatic bioenergetic network regulation might thus be used as
      an innovative strategy for the control of pharmacoresistant seizures. Recent
      focal adenosine augmentation strategies support the feasibility of this strategy.

PMID- 21731577
TI  - JC virus-induced Progressive Multifocal Leukoencephalopathy.
AB  - Progressive multifocal encephalopathy (PML) is a fatal demyelinating disease of
      the central nervous system (CNS), caused by the lytic infection of
      oligodendrocytes by a human polyomavirus, JC virus (JCV). PML is rare disease but
      mostly develops in patients with underlying immunosuppressive conditions,
      including Hodgkin's lymphoma, lymphoproliferative diseases, in those undergoing
      antineoplastic therapy and AIDS. However, consistent with the occurrence of PML
      under immunocompromised conditions, this disease seems to be also steadily
      increasing among autoimmune disease patients (multiple sclerosis and Crohn's
      disease), who are treated with antibody-based regimens (natalizumab, efalizumab
      and rituximab). This unexpected occurrence of the disease among such a patient
      population reconfirms the existence of a strong link between the underlying
      immunosuppressive conditions and development of PML. These recent observations
      have generated a new interest among investigators to further examine the unique
      biology of JCV.

PMID- 21731578
TI  - Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of
      HIV-1 infection in adults.
AB  - In the past 15 years, improvements in the management of HIV infection have
      dramatically reduced morbidity and mortality. Similarly, rapid advances in
      antiretroviral medications have resulted in the possibility of life-long therapy
      with simple and tolerable regimens. Protease inhibitors have been important
      medications in regimens of combination antiretroviral therapy for the treatment
      of HIV. One of the recommended and commonly used therapies in this class is once
      daily-administered atazanavir, pharmacologically boosted with ritonavir
      (atazanavir/r). Clinical studies and practice have shown these drugs, in
      combination with other antiretroviral agents, to be potent, safe and easy to use
      in a variety of settings. Atazanavir/r has minimal short-term toxicity, including
      benign bilirubin elevation, and has less potential for long-term complications of
      hyperlipidemia and insulin resistance compared with other protease inhibitors. A
      high genetic barrier to resistance and a favorable resistance profile make it an
      excellent option for initial HIV treatment or as the first drug utilized in the
      protease inhibitors class. Atazanavir/r is also currently being studied in novel
      treatment strategies, including combinations with new classes of antiretrovirals
      to assess nucleoside reverse transcriptase inhibitor-sparing regimens. In this
      article we review atazanavir/r as a treatment for HIV infection and discuss the
      latest information on its pharmacology, efficacy and toxicity.

PMID- 21731579
TI  - Follow your heart: Emotion adaptively influences perception.
AB  - The current review introduces a new program of research that suggests the
      perception of spatial layout is influenced by emotions. Though perceptual systems
      are often described as closed and insulated, this review presents research
      suggesting that a variety of induced emotions (e.g., fear, disgust, sadness) can
      produce changes in vision and audition. Thus, the perceptual system may be highly
      interconnected, allowing emotional information to influence perceptions that, in
      turn, influence cognition. The body of work presented here also suggests that
      emotion-based changes in perception help us solve particular adaptive problems
      because emotion does not change all perceptions of the world. Taking the adaptive
      significance of emotion into account allows us to make predictions about when and
      how emotion influences perception.

PMID- 21731580
TI  - SI RLTD: Risk Scores and Decision Making: The Anatomy of a Decision to Reduce
      Breast Cancer Risk.
AB  - AIM: To report the use of a risk score for risk treatment decision-making in
      women at risk for breast cancer in order to better understand their decision
      making situation.  BACKGROUND: Tamoxifen and Raloxifene are medications that have
      been proven to reduce the risk of breast cancer. However, women who understand
      their personal net benefit from Tamoxifen use chose not to take the medication.
      To understand this decision, the paper investigates the use of epidemiological
      risk information in the decision-making process for risk-reducing treatments. 
      METHODS: The narratives of two women are analyzed as they recall their risk score
      and explain their decision-making process concerning participation in the Study
      of Tamoxifen and Raloxifene (STAR). Both in-depth interviews follow a narrative
      approach and were recorded in a U.S. cancer center in 2005.  RESULTS: Thinking
      about risk by analyzing the chances of developing a disease is specific to
      complex decision-making situations. The associated risk-benefit analysis has to
      be conducted qualitatively as epidemiological risk information cannot know all
      details of a woman's life. In addition, a woman's decision is based on the
      perception of the condition as risk or as disease. Women are willing to treat
      risk that is perceived as disease, especially when it is based on bodily
      measurements on which the treatment has an effect. Women are not willing to treat
      a risk not perceived as disease.  CONCLUSION: The net benefit of a treatment as
      calculated based on epidemiological data cannot easily be translated onto an
      individual's life. Thus, the complex experience of a woman's life at risk is
      highly important in decision-making situations.  RELEVANCE TO CLINICAL PRACTICE:
      The ambiguity of statistical risk estimates should be acknowledged and the
      women's evaluation of her risk valued in risk treatment decision-making.

PMID- 21731581
TI  - Theoretical Perspectives on Sibling Relationships.
AB  - Although siblings are a fixture of family life, research on sibling relationships
      lags behind that on other family relationships. To stimulate interest in sibling
      research and to serve as a guide for future investigations by family scholars, we
      review four theoretical psychologically oriented perspectives-(a) psychoanalytic
      evolutionary, (b) social psychological, (c) social learning, and (d) family
      ecological systems-that can inform research on sibling relationships, including
      perspectives on the nature and influences on developmental, individual, and group
      differences in sibling relationships. Given that most research on siblings has
      focused on childhood and adolescence, our review highlights these developmental
      periods, but we also incorporate the limited research on adult sibling
      relationships, including in formulating suggestions for future research on this
      fundamental family relationship.

PMID- 21731582
TI  - Mitochondrial disease mimicking Charcot-Marie Tooth disease.
AB  - Charcot-Marie tooth disease (CMT) is a heterogenous group of peripheral
      neuropathies caused by various genetic defects. Three cases of mitochondrial
      myopathy, neuropathy and gastrointestinal encephalopathy (MNGIE) which initially
      presented with a peripheral neuropathy resembling CMT are described here. The
      diagnosis in all three cases was made after they developed eye signs and
      abdominal complaints. Young patients with mutation negative CMT should be
      followed up to monitor for signs of MNGIE.

PMID- 21731583
TI  - ARHGEF9 disruption in a female patient is associated with X linked mental
      retardation and sensory hyperarousal.
AB  - We identified a female patient with mental retardation and sensory hyperarousal.
      She has a de novo paracentric inversion of one X chromosome with completely
      skewed inactivation of the normal X chromosome. We aimed to identify whether a
      single gene or gene region caused her cognitive and behavioural impairment and
      that of others. Fluorescent in situ hybridisation (FISH) showed that the
      centromeric breakpoint disrupts a single gene: ARHGEF9 (CDC42 guanine nucleotide
      exchange factor (GEF) 9). We also found that the levels of the ARHGEF9 transcript
      from the patient are 10-fold less than those found in control samples. ARHGEF9
      encodes a RhoGEF family protein: collybistin (hPEM), which is highly expressed in
      the brain. Collybistin can regulate actin cytoskeletal dynamics and may also
      modulate GABAergic and glycinergic neurotransmission through binding of a
      scaffolding protein, gephyrin, at the synapse. This potential dual role may
      explain both the mental retardation and hyperarousal observed in our patient.

PMID- 21731584
TI  - Duplication of the Williams-Beuren critical region: case report and further
      delineation of the phenotypic spectrum.
AB  - Only 12 patients with a duplication of the Williams-Beuren critical region (WBCR)
      have been reported to date, with variable developmental, psychomotor and language
      delay, in the absence of marked dysmorphic features. In this paper we present a
      new WBCR microduplication case, which supports the wide variability displayed by
      this duplication in the phenotype. The WBCR microduplication may be associated
      with autistic spectrum disorder, but most reported cases do not show this
      behavioural disorder, or may even show a hypersociable personality, as with our
      patient. From the present case and a review of the 12 previously described, we
      conclude that the phenotype associated with duplication of WBCR can affect the
      same domains as WBCR deletion, but that they cluster near the polar ends of
      social relationship (autism-like v hypersociability), language (expressive
      language impairment v "cocktail party" speech), visuospatial (severe v normal),
      mental retardation (severe v mild) and dysmorphic (severe v mild) features.

PMID- 21731585
TI  - Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical
      presentation of maternal uniparental disomy of chromosome 14.
AB  - The clinical phenotypes of maternal and paternal uniparental disomy of chromosome
      14 (UPD14) are attributed to dysregulation of imprinted genes. A large candidate
      locus exists within 14q32, under the regulation of a paternally methylated
      intergenic differentially methylated region (IG-DMR). We present a patient with
      clinical features of maternal UPD14, including growth retardation, hypotonia,
      scoliosis, small hands and feet, and advanced puberty, who had loss of
      methylation of the IG-DMR with no evidence of maternal UPD14. This case provides
      support for the hypothesis that the maternal UPD14 phenotype is due to aberrant
      gene expression within the imprinted domain at 14q32.

PMID- 21731586
TI  - Fatal encephalopathy after an isolated overdose of cocaine.
AB  - Cocaine induced brain damage can be divided into primary neurotoxic effects
      causing toxic encephalopathy, secondary effects of compromised cerebral blood
      flow in ischaemic and haemorrhagic stroke, cerebral vasculitis and vasospasm, and
      tertiary effects due to hypoxia as a result of cardiopulmonary collapse. Toxic
      leucoencephalopathy mainly affects white matter (WM) tracts serving higher
      cerebral function, thereby leading to altered personality, attention deficits and
      memory impairment in mild cases and to dementia, coma and brain death in severe
      cases. Here we describe the case of a 21-year-old man who committed suicide by
      injecting cocaine. The cocaine induced a toxic leucoencephalopathy, which was
      proven at autopsy.

PMID- 21731587
TI  - Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in
      the literature.
AB  - Patients with Turner syndrome (TS) are at risk for aortic dissection, but the
      clinical profile for those at risk is not well described. In addition to
      reporting two new cases, we performed an electronic search to identify all
      reported cases of aortic dissection associated with TS. In total, 85 cases of
      aortic dissection in TS were reported between 1961 and 2006. Dissection occurred
      at a young age, 30.7 (range 4-64) years, which is significantly earlier than its
      occurrence in the general female population (68 years). Importantly, in 11% of
      the cases, neither hypertension nor congenital heart disease were identified,
      suggesting that TS alone is an independent risk factor for aortic dissection;
      however, the cases where no risk factors were identified were very poorly
      documented. A TS aortic dissection registry has been established to determine the
      natural history and risk factors better (http://www.turnersyndrome.org/).

PMID- 21731588
TI  - A short survey on protein blocks.
AB  - Protein structures are classically described in terms of secondary structures.
      Even if the regular secondary structures have relevant physical meaning, their
      recognition from atomic coordinates has some important limitations such as
      uncertainties in the assignment of boundaries of helical and beta-strand regions.
      Further, on an average about 50% of all residues are assigned to an irregular
      state, i.e., the coil. Thus different research teams have focused on abstracting
      conformation of protein backbone in the localized short stretches. Using
      different geometric measures, local stretches in protein structures are clustered
      in a chosen number of states. A prototype representative of the local structures
      in each cluster is generally defined. These libraries of local structures
      prototypes are named as "structural alphabets". We have developed a structural
      alphabet, named Protein Blocks, not only to approximate the protein structure,
      but also to predict them from sequence. Since its development, we and other teams
      have explored numerous new research fields using this structural alphabet. We
      review here some of the most interesting applications.

PMID- 21731589
TI  - Mild Hypothermia Suppresses Calcium-Sensing Receptor (CaSR) Induction Following
      Forebrain Ischemia While Increasing GABA-B Receptor 1 (GABA-B-R1) Expression.
AB  - Hypothermia improves neurological outcome from cardiac arrest. The mechanisms of
      protection are multifold, but identifying some may be useful in exploring
      potential therapeutic targets. The extracellular calcium-sensing receptor (CaSR)
      was originally found in parathyroid cells in which the receptor senses minute
      changes in extracellular [Ca(2+)] and promotes Ca(2+) influx and intracellular
      Ca(2+) release. The CaSR is broadly expressed in the CNS and colocalized with the
      inhibitory gamma-aminobutyric acid-B receptor 1 (GABA-B-R1). In hippocampal
      neurons, GABA-B-R1 heterodimerizes with CaSR and suppresses CaSR expression. To
      study the interplay between these two receptors in the development of ischemic
      cell death and neuroprotection by hypothermia, we subjected C57/BL6 mice to
      global cerebral ischemia by performing bilateral carotid artery occlusion (10
      min) followed by reperfusion for 1-3 days with or without therapeutic hypothermia
      (33 degrees C for 3 h at the onset of reperfusion). Terminal deoxynucleotidyl
      transferase dUTP nick end labeling staining and immunohistochemistry showed that
      forebrain ischemia increased CaSR expression, decreased GABA-B-R1 expression, and
      promoted cell death. These changes were particularly evident in hippocampal
      neurons and could be reversed by mild hypothermia. The induction of CaSR, along
      with reciprocal decreases in GABA-B-R1 expression, may together potentiate
      ischemic neuronal death, suggesting a new therapeutic target for treatment of
      ischemic brain injury. 

PMID- 21731590
TI  - Inflammation of the choroid plexus and ependymal layer of the ventricle following
      intraventricular hemorrhage.
AB  - Intraventricular hemorrhage (IVH), which afflicts thousands of people of all ages
      every year, frequently results in the development of communicating hydrocephalus.
      Classically, IVH-induced hydrocephalus has been attributed to reduced resorption
      of cerebrospinal fluid (CSF) due to dysfunction of arachnoid granulations, but
      this explanation may be incomplete. We hypothesized that IVH would cause
      inflammation of the choroid plexus and of the ependymal lining of the ventricles,
      resulting in dysfunction of these barrier cells. Barrier dysfunction, in turn,
      would be expected to cause an increase in production of abnormal protein-rich CSF
      and transependymal migration of CSF. We tested this hypothesis using a rat model
      of IVH, in which 160 MUl of autologous blood was infused into the lateral
      ventricle, resulting in a twofold increase in ventricular size 48 h later. In
      this model, we found significant activation of nuclear factor kappaB (NF-kappaB)
      signaling by the CSF barrier cells of the choroid plexus and ependymal lining.
      Moreover, these inflammatory changes were associated with abnormal uptake of
      serum-derived IgG by the barrier cells, a phenomenon closely linked to abnormal
      permeability of the blood-brain barrier. We conclude that inflammation marked by
      NF-kappaB signaling is a prominent feature after IVH and may account for certain
      pathophysiological sequelae associated with IVH. 

PMID- 21731591
TI  - Mindfulness Research Guide: a New Paradigm for Managing Empirical Health
      Information.
AB  - Scientific knowledge of human health continues to grow substantially through
      publication in empirical journals. These journals, which serve as the warehouses
      of scientific knowledge, continue to publish vast amounts of empirical
      information. This abundance of information, which promotes an understanding of
      and advances in human health, is also a precursor of information overload that
      can result in unintended and negative effects in both empirical and applied
      fields. Researchers and practitioners also struggle with this abundance as they
      are often pressured by an inability to stay abreast with the vast influx of
      current information. I offer a brief discussion of a new paradigm to manage
      empirical health information. The Mindfulness Research Guide serves as a case
      example for use as a publicly available specialized electronic information
      management system that endeavors to manage, organize, centralize, and deliver a
      wide range of information on a specific health construct-mindfulness. As
      empirical information continues to accumulate and guide our knowledge of human
      health at an unprecedented pace, new information management paradigms such as the
      Mindfulness Research Guide will be needed to organize, maintain, and deliver
      information in an easily accessible and timely fashion.

PMID- 21731592
TI  - Cost-effectiveness of varenicline and three different behavioral treatment
      formats for smoking cessation.
AB  - There is a lack of evidence of the relative cost-effectiveness of proactive
      telephone counseling (PTC) and Web-based delivery of smoking cessation services
      in conjunction with pharmacotherapy. We calculated the differential cost
      effectiveness of three behavioral smoking cessation modalities with varenicline
      treatment in a randomized trial of current smokers from a large health system.
      Eligible participants were randomized to one of three smoking cessation
      interventions: Web-based counseling (n=401), PTC (n=402), or combined PTC-Web
      counseling (n=399). All participants received a standard 12-week course of
      varenicline. The primary outcome was a 7-day point prevalent nonsmoking at the
      6month follow-up. The Web intervention was the least expensive followed by the
      PTC and PTC-Web groups. Costs per additional 6-month nonsmoker and per additional
      lifetime quitter were $1,278 and $2,601 for Web, $1,472 and $2,995 for PTC, and
      $1,617 and $3,291 for PTC-Web. Cost per life-year (LY) and quality-adjusted life
      year (QALY) saved were $1,148 and $1,136 for Web, $1,320 and $1,308 for PTC, and
      $1,450 and $1,437 for PTC-Web. Based on the cost per LY and QALY saved, these
      interventions are among the most cost-effective life-saving medical treatments.
      Web, PTC, and combined PTC-Web treatments were all highly cost-effective, with
      the Web treatment being marginally more cost-effective than the PTC or combined
      PTC-Web treatments.

PMID- 21731593
TI  - Spiritual Well-Being and Health-Related Quality of Life Among African-American
      Women with HIV/AIDS.
AB  - Many HIV-positive women regard spirituality as an important part of their lives
      and spirituality may have positive impact on their health-related quality of life
      (HRQOL). Particularly among African American women with HIV, spirituality may
      serve as a cultural and psychological resource. This descriptive, crosssectional
      study examined associations between spiritual well-being (SWB) and its
      components, existential well-being (EWB) and religious well-being (RWB), and
      dimensions of HRQOL among a non-random sample of 118 African American HIV
      positive women. A secondary analysis of data from two similar, NIH-funded
      studies: The Get Busy Living (GBL) Project and the KHARMA Project, was conducted.
      Baseline data on women from both studies were combined into one database and
      statistical analyses, including descriptive, correlation and hierarchical
      regression analyses, were conducted. Existential well-being was significantly
      positively (beta =.74; p=.014) associated with the physical composite of HRQOL
      and accounted for a significant amount of unique variance (10.0%) beyond that
      explained by socio-demographic variables, religious well-being (RWB), HIV
      medication adherence, CD4 cell count and percentage, HIV viral load, and
      depressive symptoms. EWB was also significantly positively (beta =.57; p=.024)
      associated with the mental health composite of HRQOL. Depressive symptomatology
      was also significantly inversely (beta =.40; p=.004) associated with mental
      HRQOL. EWB accounted for a significant amount of additional variance (6.3%)
      beyond that explained by other variables. Spirituality is an important factor in
      the lives and quality of life of African American women and women living with
      HIV/AIDS. Further research is needed to examine relationships between
      spirituality and HRQOL among HIV-positive African American women.

PMID- 21731594
TI  - Selected Health Conditions Among Overweight, Obese, and Non-Obese Veterans of the
      1991 Gulf War: Results from a Survey Conducted in 2003-2005.
AB  - BACKGROUND: Several health conditions and concerns have been reported to be
      increased among Gulf War veterans including post-traumatic stress disorder
      (PTSD), chronic fatigue syndrome (CFS), CFS-like illness, and unexplained multi
      symptom illness (MSI). As the cohort of Gulf War veterans advance in age, they
      are likely to be at risk of not only certain deployment-related health conditions
      but also chronic diseases associated with lifestyle factors.  METHODS: To clarify
      relationships between PTSD, CFS-like illness, MSI, and obesity, we analyzed data
      from a cross-sectional survey of health information among population-based
      samples of 15,000 Gulf War veterans and 15,000 veterans who served during the
      same era. Data had been collected from 9,970 respondents in 2003-2005 via a
      structured questionnaire or telephone survey.  RESULTS: Based upon body mass
      index (BMI) estimated from self-reported information about height and weight, the
      percentages of Gulf War and Gulf Era veterans who were overweight (BMI 25 to <=
      29.9), were 46.8% and 48.7%, respectively. The percentages who were obese (BMI >=
      30) were 29.6% and 28.3%, respectively. Without adjustment for Gulf deployment
      status (Gulf War vs Gulf Era), age, sex, or other factors, PTSD, MSI, CFS-like
      illness, and other chronic health conditions were more common among obese
      veterans than those who were normal weight (BMI 18.5 to <= 24.9). In multivariate
      analyses, PTSD was positively associated with obesity after adjustment for age,
      sex, Gulf deployment status, rank, income, education, and current smoking. In the
      model for PTSD, the adjusted odds ratio for obesity was 1.5 (95% CI 1.2-1.8). No
      associations were observed between BMI categories and CFS-like illness or MSI in
      multivariate analysis.  CONCLUSIONS: Gulf War and Gulf Era veterans who were
      obese were more likely to have certain chronic health conditions including PTSD.
      Associations between Gulf status and CFS-like illness and MSI identified in the
      2003-2005 follow-up survey were not accounted for by group differences in the
      prevalence of overweight or obesity.

PMID- 21731595
TI  - PolyAna: analyzing synonymous and nonsynonymous polymorphic sites.
AB  - PolyAna (available at http://www.biol.sc.edu/~austin/) aids in the analysis of
      natural selection on protein-coding sequences by estimating sample gene diversity
      at individual polymorphic nucleotide sites, which are classified as synonymous,
      non-synonymous, or ambiguous.

PMID- 21731596
TI  - Advances in the Pharmacologic Management of Atrial Fibrillation.

PMID- 21731597
TI  - Model for biological communication in a nanofabricated cell-mimic driven by
      stochastic resonance.
AB  - Cells offer natural examples of highly efficient networks of nanomachines.
      Accordingly, both intracellular and intercellular communication mechanisms in
      nature are looked to as a source of inspiration and instruction for engineered
      nanocommunication. Harnessing biological functionality in this manner requires an
      interdisciplinary approach that integrates systems biology, synthetic biology,
      and nanofabrication. Here, we present a model system that exemplifies the
      synergism between these realms of research. We propose a synthetic gene network
      for operation in a nanofabricated cell mimic array that propagates a biomolecular
      signal over long distances using the phenomenon of stochastic resonance. Our
      system consists of a bacterial quorum sensing signal molecule, a bistable genetic
      switch triggered by this signal, and an array of nanofabricated cell mimic wells
      that contain the genetic system. An optimal level of noise in the system helps to
      propagate a time-varying AHL signal over long distances through the array of
      mimics. This noise level is determined both by the system volume and by the
      parameters of the genetic network. Our proposed genetically driven stochastic
      resonance system serves as a testbed for exploring the potential harnessing of
      gene expression noise to aid in the transmission of a time-varying molecular
      signal.

PMID- 21731598
TI  - Temporal dynamics reveal atypical brain response to social exclusion in autism.
AB  - Despite significant social difficulties, children with autism spectrum disorder
      (ASD) are vulnerable to the effects of social exclusion. We recorded EEG while
      children with ASD and typical peers played a computerized game involving peer
      rejection. Children with ASD reported ostracism-related distress comparable to
      typically developing children. Event-related potentials (ERPs) indicated a
      distinct pattern of temporal processing of rejection events in children with ASD.
      While typically developing children showed enhanced response to rejection at a
      late slow wave indexing emotional arousal and regulation, those with autism
      showed attenuation at an early component, suggesting reduced engagement of
      attentional resources in the aversive social context. Results emphasize the
      importance of studying the time course of social information processing in ASD;
      they suggest distinct mechanisms subserving similar overt behavior and yield
      insights relevant to development and implementation of targeted treatment
      approaches and objective measures of response to treatment.

PMID- 21731599
TI  - Using novel control groups to dissect the amygdala's role in Williams syndrome.
AB  - Williams syndrome is a neurodevelopmental disorder with an intriguing behavioral
      phenotype-hypersociability combined with significant non-social fears. Previous
      studies have demonstrated abnormalities in amygdala function in individuals with
      Williams syndrome compared to typically-developing controls. However, it remains
      unclear whether the findings are related to the atypical neurodevelopment of
      Williams syndrome, or are also associated with behavioral traits at the extreme
      end of a normal continuum. We used functional magnetic resonance imaging (fMRI)
      to compare amygdala blood-oxygenation-level-dependent (BOLD) responses to non
      social and social images in individuals with Williams syndrome compared to either
      individuals with inhibited temperament (high non-social fear) or individuals with
      uninhibited temperament (high sociability). Individuals with Williams syndrome
      had larger amygdala BOLD responses when viewing the non-social fear images than
      the inhibited temperament control group. In contrast, when viewing both fear and
      neutral social images, individuals with Williams syndrome did not show smaller
      amygdala BOLD responses relative to the uninhibited temperament control group,
      but instead had amygdala responses proportionate to their sociability. These
      results suggest heightened amygdala response to non-social fear images is
      characteristic of WS, whereas, variability in amygdala response to social fear
      images is proportionate to, and might be explained by, levels of trait
      sociability.

PMID- 21731601
TI  - Specific syndecan-1 domains regulate mesenchymal tumor cell adhesion, motility
      and migration.
AB  - BACKGROUND: Syndecans are proteoglycans whose core proteins have a short
      cytoplasmic domain, a transmembrane domain and a large N-terminal extracellular
      domain possessing glycosaminoglycan chains. Syndecans are involved in many
      important cellular processes. Our recent publications have demonstrated that
      syndecan-1 translocates into the nucleus and hampers tumor cell proliferation. In
      the present study, we aimed to investigate the role of syndecan-1 in tumor cell
      adhesion and migration, with special focus on the importance of its distinct
      protein domains, to better understand the structure-function relationship of
      syndecan-1 in tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: We utilized two
      mesenchymal tumor cell lines which were transfected to stably overexpress full
      length syndecan-1 or truncated variants: the 78 which lacks the extracellular
      domain except the DRKE sequence proposed to be essential for oligomerization, the
      77 which lacks the whole extracellular domain, and the RMKKK which serves as a
      nuclear localization signal. The deletion of the RMKKK motif from full-length
      syndecan-1 abolished the nuclear translocation of this proteoglycan. Various
      bioassays for cell adhesion, chemotaxis, random movement and wound healing were
      studied. Furthermore, we performed gene microarray to analyze the global gene
      expression pattern influenced by syndecan-1. Both full-length and truncated
      syndecan-1 constructs decrease tumor cell migration and motility, and affect cell
      adhesion. Distinct protein domains have differential effects, the extracellular
      domain is more important for promoting cell adhesion, while the transmembrane and
      cytoplasmic domains are sufficient for inhibition of cell migration. Cell
      behavior seems to depend also on the nuclear translocation of syndecan-1. Many
      genes are differentially regulated by syndecan-1 and a number of genes are
      actually involved in cell adhesion and migration. CONCLUSIONS/SIGNIFICANCE: Our
      results demonstrate that syndecan-1 regulates mesenchymal tumor cell adhesion and
      migration, and different domains have differential effects. Our study provides
      new insights into better understanding of the role of syndecans in tumor
      progression.

PMID- 21731602
TI  - Screening for acute childhood malnutrition during the National Nutrition Week in
      mali increases treatment referrals.
AB  - OBJECTIVE: To evaluate a pilot intervention designed to integrate mid-upper arm
      circumference (MUAC) screening for acute malnutrition into the semi-annual Child
      Nutrition Week (Semaine d'Intensification des Activites de Nutrition, or "SIAN")
      activities carried out in June 2008. DESIGN: A cross-sectional survey was
      conducted in Kolokani and Nara, two health districts in the Koulikoro region of
      Mali, 4-5 months after the SIAN, using a population-proportionate, multi-stage
      random sample of: 1) health centers, and 2) households in communities linked to
      each of the selected health centers. Caregivers of 1543 children who were 6-59
      months of age at the time of the SIAN, 17 community-based volunteers and 45
      health center staff members were interviewed. RESULTS: A total of 1278 children 6
      59 months (83% of those studied) reportedly participated in SIAN. Of the
      participating children, 1258 received vitamin A (98% of SIAN participants; 82% of
      all eligible children), 945 received anti-helminth tablets (84% of participants;
      71% of eligibles), and 669 were screened for acute malnutrition (52% of
      participants; 43% of eligibles). 186 of the children screened (27%) were
      reportedly identified as acutely malnourished. SIAN screening covered a
      significantly greater proportion of children than were examined in both community
      based (22% of children) and health center-based screening activities (5% of
      children) combined during the 4-5 months after the SIAN (P<0.0001). In general,
      community volunteers and health personnel positively evaluated their experience
      adding MUAC screening to SIAN. CONCLUSION: Integrating MUAC screening for acute
      malnutrition in SIAN permits the assessment of a large number of children for
      acute malnutrition, and should be continued.

PMID- 21731603
TI  - Epigenetic predictor of age.
AB  - From the moment of conception, we begin to age. A decay of cellular structures,
      gene regulation, and DNA sequence ages cells and organisms. DNA methylation
      patterns change with increasing age and contribute to age related disease. Here
      we identify 88 sites in or near 80 genes for which the degree of cytosine
      methylation is significantly correlated with age in saliva of 34 male identical
      twin pairs between 21 and 55 years of age. Furthermore, we validated sites in the
      promoters of three genes and replicated our results in a general population
      sample of 31 males and 29 females between 18 and 70 years of age. The methylation
      of three sites--in the promoters of the EDARADD, TOM1L1, and NPTX2 genes--is
      linear with age over a range of five decades. Using just two cytosines from these
      loci, we built a regression model that explained 73% of the variance in age, and
      is able to predict the age of an individual with an average accuracy of 5.2
      years. In forensic science, such a model could estimate the age of a person,
      based on a biological sample alone. Furthermore, a measurement of relevant sites
      in the genome could be a tool in routine medical screening to predict the risk of
      age-related diseases and to tailor interventions based on the epigenetic bio-age
      instead of the chronological age.

PMID- 21731604
TI  - Dietary intake and rural-urban migration in India: a cross-sectional study.
AB  - BACKGROUND: Migration from rural areas of India contributes to urbanisation and
      lifestyle change, and dietary changes may increase the risk of obesity and
      chronic diseases. We tested the hypothesis that rural-to-urban migrants have
      different macronutrient and food group intake to rural non-migrants, and that
      migrants have a diet more similar to urban non-migrants. METHODS AND FINDINGS:
      The diets of migrants of rural origin, their rural dwelling sibs, and those of
      urban origin together with their urban dwelling sibs were assessed by an
      interviewer-administered semi-quantitative food frequency questionnaire. A total
      of 6,509 participants were included. Median energy intake in the rural, migrant
      and urban groups was 2731, 3078, and 3224 kcal respectively for men, and 2153,
      2504, and 2644 kcal for women (p<0.001). A similar trend was seen for overall
      intake of fat, protein and carbohydrates (p<0.001), though differences in the
      proportion of energy from these nutrients were <2%. Migrant and urban
      participants reported up to 80% higher fruit and vegetable intake than rural
      participants (p<0.001), and up to 35% higher sugar intake (p<0.001). Meat and
      dairy intake were higher in migrant and urban participants than rural
      participants (p<0.001), but varied by region. Sibling-pair analyses confirmed
      these results. There was no evidence of associations with time in urban area.
      CONCLUSIONS: Rural to urban migration appears to be associated with both positive
      (higher fruit and vegetables intake) and negative (higher energy and fat intake)
      dietary changes. These changes may be of relevance to cardiovascular health and
      warrant public health interventions.

PMID- 21731605
TI  - Association between plasma antibody response and protection in rainbow trout
      Oncorhynchus mykiss immersion vaccinated against Yersinia ruckeri.
AB  - A key hallmark of the vertebrate adaptive immune system is the generation of
      antigen-specific antibodies from B cells. Fish are the most primitive
      gnathostomes (jawed vertebrates) possessing an adaptive immune system.
      Vaccination of rainbow trout against enteric redmouth disease (ERM) by immersion
      in Yersinia ruckeri bacterin confers a high degree of protection to the fish. The
      immune mechanisms responsible for protection may comprise both cellular and
      humoral elements but the role of specific immunoglobulins in this system has been
      questioned and not previously described. The present study demonstrates
      significant increase in plasma antibody titers following immersion vaccination
      and significantly reduced mortality during Y. ruckeri challenge.Rainbow trout
      were immersion-vaccinated, using either a commercial ERM vaccine (AquaVacTM ERM
      vet) or an experimental Y. ruckeri bacterin. Half of the trout vaccinated with
      AquaVacTM ERM vet received an oral booster (AquaVacTM ERM Oral vet). Sub-groups
      of the fish from each group were subsequently exposed to 1 x 109 CFU Y.
      ruckeri/ml either eight or twenty-six weeks post vaccination (wpv). All
      vaccinated groups showed 0% mortality when challenged, which was highly
      significant compared to the non-vaccinated controls (40 and 28% mortality eight
      and twenty-six weeks post vaccination (wpv), respectively) (P<0.0001). Plasma
      samples from all groups of vaccinated fish were taken 0, 4, 8, 12, 16 and 26 wpv.
      and Y. ruckeri specific IgM antibody levels were measured with ELISA. A
      significant increase in titers was recorded in vaccinated fish, which also showed
      a reduced bacteremia during challenge. In vitro plasma studies showed a
      significantly increased bactericidal effect of fresh plasma from vaccinated fish
      indicating that plasma proteins may play a role in protection of vaccinated
      rainbow trout.

PMID- 21731606
TI  - The utility of high-resolution melting analysis of SNP nucleated PCR amplicons-
      an MLST based Staphylococcus aureus typing scheme.
AB  - High resolution melting (HRM) analysis is gaining prominence as a method for
      discriminating DNA sequence variants. Its advantage is that it is performed in a
      real-time PCR device, and the PCR amplification and HRM analysis are closed tube,
      and effectively single step. We have developed an HRM-based method for
      Staphylococcus aureus genotyping. Eight single nucleotide polymorphisms (SNPs)
      were derived from the S. aureus multi-locus sequence typing (MLST) database on
      the basis of maximized Simpson's Index of Diversity. Only G<->A, G<->T, C<->A, C<
      >T SNPs were considered for inclusion, to facilitate allele discrimination by
      HRM. In silico experiments revealed that DNA fragments incorporating the SNPs
      give much higher resolving power than randomly selected fragments. It was shown
      that the predicted optimum fragment size for HRM analysis was 200 bp, and that
      other SNPs within the fragments contribute to the resolving power. Six DNA
      fragments ranging from 83 bp to 219 bp, incorporating the resolution optimized
      SNPs were designed. HRM analysis of these fragments using 94 diverse S. aureus
      isolates of known sequence type or clonal complex (CC) revealed that sequence
      variants are resolved largely in accordance with G+C content. A combination of
      experimental results and in silico prediction indicates that HRM analysis
      resolves S. aureus into 268 "melt types" (MelTs), and provides a Simpson's Index
      of Diversity of 0.978 with respect to MLST. There is a high concordance between
      HRM analysis and the MLST defined CCs. We have generated a Microsoft Excel key
      which facilitates data interpretation and translation between MelT and MLST data.
      The potential of this approach for genotyping other bacterial pathogens was
      investigated using a computerized approach to estimate the densities of SNPs with
      unlinked allelic states. The MLST databases for all species tested contained
      abundant unlinked SNPs, thus suggesting that high resolving power is not
      dependent upon large numbers of SNPs.

PMID- 21731607
TI  - High-level fluorescence labeling of gram-positive pathogens.
AB  - Fluorescence labeling of bacterial pathogens has a broad range of interesting
      applications including the observation of living bacteria within host cells. We
      constructed a novel vector based on the E. coli streptococcal shuttle plasmid
      pAT28 that can propagate in numerous bacterial species from different genera. The
      plasmid harbors a promoterless copy of the green fluorescent variant gene egfp
      under the control of the CAMP-factor gene (cfb) promoter of Streptococcus
      agalactiae and was designated pBSU101. Upon transfer of the plasmid into
      streptococci, the bacteria show a distinct and easily detectable fluorescence
      using a standard fluorescence microscope and quantification by FACS-analysis
      demonstrated values that were 10-50 times increased over the respective controls.
      To assess the suitability of the construct for high efficiency fluorescence
      labeling in different gram-positive pathogens, numerous species were transformed.
      We successfully labeled Streptococcus pyogenes, Streptococcus agalactiae,
      Streptococcus dysgalactiae subsp. equisimilis, Enterococcus faecalis,
      Enterococcus faecium, Streptococcus mutans, Streptococcus anginosus and
      Staphylococcus aureus strains utilizing the EGFP reporter plasmid pBSU101. In all
      of these species the presence of the cfb promoter construct resulted in high
      level EGFP expression that could be further increased by growing the
      streptococcal and enterococcal cultures under high oxygen conditions through
      continuous aeration.

PMID- 21731608
TI  - HMGB1 attenuates cardiac remodelling in the failing heart via enhanced cardiac
      regeneration and miR-206-mediated inhibition of TIMP-3.
AB  - AIMS: HMGB1 injection into the mouse heart, acutely after myocardial infarction
      (MI), improves left ventricular (LV) function and prevents remodeling. Here, we
      examined the effect of HMGB1 in chronically failing hearts. METHODS AND RESULTS:
      Adult C57 BL16 female mice underwent coronary artery ligation; three weeks later
      200 ng HMGB1 or denatured HMGB1 (control) were injected in the peri-infarcted
      region of mouse failing hearts. Four weeks after treatment, both echocardiography
      and hemodynamics demonstrated a significant improvement in LV function in HMGB1
      treated mice. Further, HMGB1-treated mice exhibited a ~23% reduction in LV
      volume, a ~48% increase in infarcted wall thickness and a ~14% reduction in
      collagen deposition. HMGB1 induced cardiac regeneration and, within the infarcted
      region, it was found a ~2-fold increase in c-kit+ cell number, a ~13-fold
      increase in newly formed myocytes and a ~2-fold increase in arteriole length
      density. HMGB1 also enhanced MMP2 and MMP9 activity and decreased TIMP-3 levels.
      Importantly, miR-206 expression 3 days after HMGB1 treatment was 4-5-fold higher
      than in control hearts and 20-25 fold higher that in sham operated hearts. HMGB1
      ability to increase miR-206 was confirmed in vitro, in cardiac fibroblasts. TIMP3
      was identified as a potential miR-206 target by TargetScan prediction analysis;
      further, in cultured cardiac fibroblasts, miR-206 gain- and loss-of-function
      studies and luciferase reporter assays showed that TIMP3 is a direct target of
      miR-206. CONCLUSIONS: HMGB1 injected into chronically failing hearts enhanced LV
      function and attenuated LV remodelling; these effects were associated with
      cardiac regeneration, increased collagenolytic activity, miR-206 overexpression
      and miR-206 -mediated inhibition of TIMP-3.

PMID- 21731609
TI  - Body mass index and diabetes in Asia: a cross-sectional pooled analysis of
      900,000 individuals in the Asia cohort consortium.
AB  - BACKGROUND: The occurrence of diabetes has greatly increased in low- and middle
      income countries, particularly in Asia, as has the prevalence of overweight and
      obesity; in European-derived populations, overweight and obesity are established
      causes of diabetes. The shape of the association of overweight and obesity with
      diabetes risk and its overall impact have not been adequately studied in Asia.
      METHODS AND FINDINGS: A pooled cross-sectional analysis was conducted to evaluate
      the association between baseline body mass index (BMI, measured as weight in kg
      divided by the square of height in m) and self-reported diabetes status in over
      900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan,
      Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate
      cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI,
      after adjustment for potential confounding factors. OR were pooled across cohorts
      using a random-effects meta-analysis. The sex- and age-adjusted prevalence of
      diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across
      participating cohorts. Using the category 22.5-24.9 kg/m2) as reference, the OR
      for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI
      lower than 15.0 kg/m2 to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m2.
      The positive association between BMI and diabetes prevalence was present in all
      cohorts and in all subgroups of the study population, although the association
      was stronger in individuals below age 50 at baseline (p-value of
      interaction<0.001), in cohorts from India and Bangladesh (p<0.001), in
      individuals with low education (p-value 0.02), and in smokers (p-value 0.03); no
      differences were observed by gender, urban residence, or alcohol drinking.
      CONCLUSIONS: This study estimated the shape and the strength of the association
      between BMI and prevalence of diabetes in Asian populations and identified
      patterns of the association by age, country, and other risk factors for diabetes.

PMID- 21731610
TI  - RosettaScripts: a scripting language interface to the Rosetta macromolecular
      modeling suite.
AB  - Macromolecular modeling and design are increasingly useful in basic research,
      biotechnology, and teaching. However, the absence of a user-friendly modeling
      framework that provides access to a wide range of modeling capabilities is
      hampering the wider adoption of computational methods by non-experts.
      RosettaScripts is an XML-like language for specifying modeling tasks in the
      Rosetta framework. RosettaScripts provides access to protocol-level
      functionalities, such as rigid-body docking and sequence redesign, and allows
      fast testing and deployment of complex protocols without need for modifying or
      recompiling the underlying C++ code. We illustrate these capabilities with
      RosettaScripts protocols for the stabilization of proteins, the generation of
      computationally constrained libraries for experimental selection of higher
      affinity binding proteins, loop remodeling, small-molecule ligand docking, design
      of ligand-binding proteins, and specificity redesign in DNA-binding proteins.

PMID- 21731611
TI  - HSPB1, HSPB6, HSPB7 and HSPB8 protect against RhoA GTPase-induced remodeling in
      tachypaced atrial myocytes.
AB  - BACKGROUND: We previously demonstrated the small heat shock protein, HSPB1, to
      prevent tachycardia remodeling in in vitro and in vivo models for Atrial
      Fibrillation (AF). To gain insight into its mechanism of action, we examined the
      protective effect of all 10 members of the HSPB family on tachycardia remodeling.
      Furthermore, modulating effects of HSPB on RhoA GTPase activity and F-actin
      stress fiber formation were examined, as this pathway was found of prime
      importance in tachycardia remodeling events and the initiation of AF. METHODS AND
      RESULTS: Tachypacing (4 Hz) of HL-1 atrial myocytes significantly and
      progressively reduced the amplitude of Ca2+ transients (CaT). In addition to
      HSPB1, also overexpression of HSPB6, HSPB7 and HSPB8 protected against
      tachypacing-induced CaT reduction. The protective effect was independent of
      HSPB1. Moreover, tachypacing induced RhoA GTPase activity and caused F-actin
      stress fiber formation. The ROCK inhibitor Y27632 significantly prevented
      tachypacing-induced F-actin formation and CaT reductions, showing that RhoA
      activation is required for remodeling. Although all protective HSPB members
      prevented the formation of F-actin stress fibers, their mode of action differs.
      Whilst HSPB1, HSPB6 and HSPB7 acted via direct prevention of F-actin formation,
      HSPB8-protection was mediated via inhibition of RhoA GTPase activity. CONCLUSION:
      Overexpression of HSPB1, as well as HSPB6, HSPB7 and HSPB8 independently protect
      against tachycardia remodeling by attenuation of the RhoA GTPase pathway at
      different levels. The cardioprotective role for multiple HSPB members indicate a
      possible therapeutic benefit of compounds able to boost the expression of single
      or multiple members of the HSPB family.

PMID- 21731612
TI  - Increased secreted amyloid precursor protein-alpha (sAPPalpha) in severe autism:
      proposal of a specific, anabolic pathway and putative biomarker.
AB  - Autism is a neurodevelopmental disorder characterized by deficits in verbal
      communication, social interactions, and the presence of repetitive, stereotyped
      and compulsive behaviors. Excessive early brain growth is found commonly in some
      patients and may contribute to disease phenotype. Reports of increased levels of
      brain-derived neurotrophic factor (BDNF) and other neurotrophic-like factors in
      autistic neonates suggest that enhanced anabolic activity in CNS mediates this
      overgrowth effect. We have shown previously that in a subset of patients with
      severe autism and aggression, plasma levels of the secreted amyloid-beta (Abeta)
      precursor protein-alpha form (sAPPalpha) were significantly elevated relative to
      controls and patients with mild-to-moderate autism. Here we further tested the
      hypothesis that levels of sAPPalpha and sAPPbeta (proteolytic cleavage products
      of APP by alpha- and beta-secretase, respectively) are deranged in autism and may
      contribute to an anabolic environment leading to brain overgrowth. We measured
      plasma levels of sAPPalpha, sAPPbeta, Abeta peptides and BDNF by corresponding
      ELISA in a well characterized set of subjects. We included for analysis 18
      control, 6 mild-to-moderate, and 15 severely autistic patient plasma samples. We
      have observed that sAPPalpha levels are increased and BDNF levels decreased in
      the plasma of patients with severe autism as compared to controls. Further, we
      show that Abeta1-40, Abeta1-42, and sAPPbeta levels are significantly decreased
      in the plasma of patients with severe autism. These findings do not extend to
      patients with mild-to-moderate autism, providing a biochemical correlate of
      phenotypic severity. Taken together, this study provides evidence that sAPPalpha
      levels are generally elevated in severe autism and suggests that these patients
      may have aberrant non-amyloidogenic processing of APP.

PMID- 21731613
TI  - Blood signature of pre-heart failure: a microarrays study.
AB  - BACKGROUND: The preclinical stage of systolic heart failure (HF), known as
      asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by
      echocardiography, frequent in the general population and leads to a high risk of
      developing severe HF. Large scale screening for ALVD is a difficult task and
      represents a major unmet clinical challenge that requires the determination of
      ALVD biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: 294 individuals were screened by
      echocardiography. We identified 9 ALVD cases out of 128 subjects with
      cardiovascular risk factors. White blood cell gene expression profiling was
      performed using pangenomic microarrays. Data were analyzed using principal
      component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build
      an ALVD classifier model, we used the nearest centroid classification method
      (NCCM) with the ClaNC software package. Classification performance was determined
      using the leave-one-out cross-validation method. Blood transcriptome analysis
      provided a specific molecular signature for ALVD which defined a model based on 7
      genes capable of discriminating ALVD cases. Analysis of an ALVD patients
      validation group demonstrated that these genes are accurate diagnostic predictors
      for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating
      Characteristic curves of expression levels confirmed that 6 out of 7 genes
      discriminate for left ventricular dysfunction classification.
      CONCLUSIONS/SIGNIFICANCE: These targets could serve to enhance the ability to
      efficiently detect ALVD by general care practitioners to facilitate preemptive
      initiation of medical treatment preventing the development of HF.

PMID- 21731614
TI  - Modeling symmetric macromolecular structures in Rosetta3.
AB  - Symmetric protein assemblies play important roles in many biochemical processes.
      However, the large size of such systems is challenging for traditional structure
      modeling methods. This paper describes the implementation of a general framework
      for modeling arbitrary symmetric systems in Rosetta3. We describe the various
      types of symmetries relevant to the study of protein structure that may be
      modeled using Rosetta's symmetric framework. We then describe how this symmetric
      framework is efficiently implemented within Rosetta, which restricts the
      conformational search space by sampling only symmetric degrees of freedom, and
      explicitly simulates only a subset of the interacting monomers. Finally, we
      describe structure prediction and design applications that utilize the Rosetta3
      symmetric modeling capabilities, and provide a guide to running simulations on
      symmetric systems.

PMID- 21731615
TI  - Rate effects on timing, key velocity, and finger kinematics in piano performance.
AB  - We examined the effect of rate on finger kinematics in goal-directed actions of
      pianists. In addition, we evaluated whether movement kinematics can be treated as
      an indicator of personal identity. Pianists' finger movements were recorded with
      a motion capture system while they performed melodies from memory at different
      rates. Pianists' peak finger heights above the keys preceding keystrokes
      increased as tempo increased, and were attained about one tone before keypress.
      These rate effects were not simply due to a strategy to increase key velocity
      (associated with tone intensity) of the corresponding keystroke. Greater finger
      heights may compensate via greater tactile feedback for a speed-accuracy tradeoff
      that underlies the tendency toward larger temporal variability at faster tempi.
      This would allow pianists to maintain high temporal accuracy when playing at fast
      rates. In addition, finger velocity and accelerations as pianists' fingers
      approached keys were sufficiently unique to allow pianists' identification with a
      neural-network classifier. Classification success was higher in pianists with
      more extensive musical training. Pianists' movement "signatures" may reflect
      unique goal-directed movement kinematic patterns, leading to individualistic
      sound.

PMID- 21731616
TI  - Understory bird communities in Amazonian rainforest fragments: species turnover
      through 25 years post-isolation in recovering landscapes.
AB  - Inferences about species loss following habitat conversion are typically drawn
      from short-term surveys, which cannot reconstruct long-term temporal dynamics of
      extinction and colonization. A long-term view can be critical, however, to
      determine the stability of communities within fragments. Likewise, landscape
      dynamics must be considered, as second growth structure and overall forest cover
      contribute to processes in fragments. Here we examine bird communities in 11
      Amazonian rainforest fragments of 1-100 ha, beginning before the fragments were
      isolated in the 1980s, and continuing through 2007. Using a method that accounts
      for imperfect detection, we estimated extinction and colonization based on
      standardized mist-net surveys within discreet time intervals (1-2 preisolation
      samples and 4-5 post-isolation samples). Between preisolation and 2007, all
      fragments lost species in an area-dependent fashion, with loss of as few as <10%
      of preisolation species from 100-ha fragments, but up to 70% in 1-ha fragments.
      Analysis of individual time intervals revealed that the 2007 result was not due
      to gradual species loss beginning at isolation; both extinction and colonization
      occurred in every time interval. In the last two samples, 2000 and 2007,
      extinction and colonization were approximately balanced. Further, 97 of 101
      species netted before isolation were detected in at least one fragment in 2007.
      Although a small subset of species is extremely vulnerable to fragmentation, and
      predictably goes extinct in fragments, developing second growth in the matrix
      around fragments encourages recolonization in our landscapes. Species richness in
      these fragments now reflects local turnover, not long-term attrition of species.
      We expect that similar processes could be operating in other fragmented systems
      that show unexpectedly low extinction.

PMID- 21731617
TI  - Poly(m-phenylenediamine) nanospheres and nanorods: selective synthesis and their
      application for multiplex nucleic acid detection.
AB  - In this paper, we demonstrate for the first time that poly(m-phenylenediamine)
      (PMPD) nanospheres and nanorods can be selectively synthesized via chemical
      oxidation polymerization of m-phenylenediamine (MPD) monomers using ammonium
      persulfate (APS) as an oxidant at room temperature. It suggests that the pH value
      plays a critical role in controlling the the morphology of the nanostructures and
      fast polymerization rate favors the anisotropic growth of PMPD under homogeneous
      nucleation condition. We further demonstrate that such PMPD nanostructures can be
      used as an effective fluorescent sensing platform for multiplex nucleic acid
      detection. A detection limit as low as 50 pM and a high selectivity down to
      single-base mismatch could be achieved. The fluorescence quenching is attributed
      to photoinduced electron transfer from nitrogen atom in PMPD to excited
      fluorophore. Most importantly, the successful use of this sensing platform in
      human blood serum system is also demonstrated.

PMID- 21731618
TI  - Quantitative whole body biodistribution of fluorescent-labeled agents by non
      invasive tomographic imaging.
AB  - When small molecules or proteins are injected into live animals, their physical
      and chemical properties will significantly affect pharmacokinetics, tissue
      penetration, and the ultimate routes of metabolism and clearance. Fluorescence
      molecular tomography (FMT) offers the ability to non-invasively image and
      quantify temporal changes in fluorescence throughout the major organ systems of
      living animals, in a manner analogous to traditional approaches with radiolabeled
      agents. This approach is best used with biotherapeutics (therapeutic antibodies,
      or other large proteins) or large-scaffold drug-delivery vectors, that are
      minimally affected by low-level fluorophore conjugation. Application to small
      molecule drugs should take into account the significant impact of fluorophore
      labeling on size and physicochemical properties, however, the presents studies
      show that this technique is readily applied to small molecule agents developed
      for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive
      FMT correlated well with both fluorescence from tissue homogenates as well as
      with planar (2D) fluorescence reflectance imaging of excised intact organs (r2  =
      0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24
      h) performed in live mice after the injection of four different FR/NIR-labeled
      agents, including immunoglobulin, 20-50 nm nanoparticles, a large vascular
      imaging agent, and a small molecule integrin antagonist, showed clear differences
      in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney,
      and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the
      small molecule integrin-binding agent favored rapid kidney and bladder clearance,
      and the vascular agent, showed both liver and kidney clearance. Further
      assessment of the volume of distribution of these agents by fluorescent volume
      added information regarding their biodistribution and highlighted the relatively
      poor extravasation into tissue by IgG1. These studies demonstrate the ability of
      quantitative FMT imaging of FR/NIR agents to non-invasively visualize and
      quantify the biodistribution of different agents over time.

PMID- 21731619
TI  - Relationship between exercise capacity and brain size in mammals.
AB  - BACKGROUND: A great deal of experimental research supports strong associations
      between exercise, cognition, neurogenesis and neuroprotection in mammals. Much of
      this work has focused on neurogenesis in individual subjects in a limited number
      of species. However, no study to date has examined the relationship between
      exercise and neurobiology across a wide range of mammalian taxa. It is possible
      that exercise and neurobiology are related across evolutionary time. To test this
      hypothesis, this study examines the association between exercise and brain size
      across a wide range of mammals. METHODOLOGY/PRINCIPAL FINDINGS: Controlling for
      associations with body size, we examined the correlation between brain size and a
      proxy for exercise frequency and capacity, maximum metabolic rate (MMR; ml O(2)
      min(-1)). We collected brain sizes and MMRs from the literature and calculated
      residuals from the least-squares regression line describing the relationship
      between body mass and each variable of interest. We then analyzed the correlation
      between residual brain size and residual MMR both before and after controlling
      for phylogeny using phylogenetic independent contrasts. We found a significant
      positive correlation between maximum metabolic rate and brain size across a wide
      range of taxa. CONCLUSIONS: These results suggest a novel hypothesis that links
      brain size to the evolution of locomotor behaviors in a wide variety of mammalian
      species. In the end, we suggest that some portion of brain size in nonhuman
      mammals may have evolved in conjunction with increases in exercise capacity
      rather than solely in response to selection related to cognitive abilities.

PMID- 21731620
TI  - Will elephants soon disappear from West African savannahs?
AB  - Precipitous declines in Africa's native fauna and flora are recognized, but few
      comprehensive records of these changes have been compiled. Here, we present
      population trends for African elephants in the 6,213,000 km2 Sudano-Sahelian
      range of West and Central Africa assessed through the analysis of aerial and
      ground surveys conducted over the past 4 decades. These surveys are focused on
      the best protected areas in the region, and therefore represent the best case
      scenario for the northern savanna elephants. A minimum of 7,745 elephants
      currently inhabit the entire region, representing a minimum decline of 50% from
      estimates four decades ago for these protected areas. Most of the historic range
      is now devoid of elephants and, therefore, was not surveyed. Of the 23 surveyed
      elephant populations, half are estimated to number less than 200 individuals.
      Historically, most populations numbering less than 200 individuals in the region
      were extirpated within a few decades. Declines differed by region, with Central
      African populations experiencing much higher declines (-76%) than those in West
      Africa (-33%). As a result, elephants in West Africa now account for 86% of the
      total surveyed. Range wide, two refuge zones retain elephants, one in West and
      the other in Central Africa. These zones are separated by a large distance (~900
      km) of high density human land use, suggesting connectivity between the regions
      is permanently cut. Within each zone, however, sporadic contacts between
      populations remain. Retaining such connectivity should be a high priority for
      conservation of elephants in this region. Specific corridors designed to reduce
      the isolation of the surveyed populations are proposed. The strong commitment of
      governments, effective law enforcement to control the illegal ivory trade and the
      involvement of local communities and private partners are all critical to
      securing the future of elephants inhabiting Africa's northern savannas.

PMID- 21731621
TI  - Incorporation of real-time PCR into routine public health surveillance of culture
      negative bacterial meningitis in Sao Paulo, Brazil.
AB  - Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is
      ideal for incorporation into routine surveillance in a developing country. We
      validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria
      meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being
      culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in
      cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%-100%) for N.
      meningitidis, 97.8% (85.5%-99.9%) for S. pneumoniae, and 66.7% (9.4%-99.2%) for
      H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to
      routine microbiologic methods increased the yield for detection of S. pneumoniae,
      N. meningitidis, and H. influenzae cases by 52%, 85%, and 20%, respectively. The
      main risk factor for being culture negative and RT-PCR positive was presence of
      antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly
      sensitive and specific and substantially added to measures of meningitis disease
      burden when incorporated into routine public health surveillance in Brazil.

PMID- 21731622
TI  - Phylogeography of a land snail suggests trans-Mediterranean neolithic transport.
AB  - BACKGROUND: Fragmented distribution ranges of species with little active
      dispersal capacity raise the question about their place of origin and the
      processes and timing of either range fragmentation or dispersal. The peculiar
      distribution of the land snail Tudorella sulcata s. str. in Southern France,
      Sardinia and Algeria is such a challenging case. METHODOLOGY: Statistical
      phylogeographic analyses with mitochondrial COI and nuclear hsp70 haplotypes were
      used to answer the questions of the species' origin, sequence and timing of
      dispersal. The origin of the species was on Sardinia. Starting from there, a
      first expansion to Algeria and then to France took place. Abiotic and zoochorous
      dispersal could be excluded by considering the species' life style, leaving only
      anthropogenic translocation as parsimonious explanation. The geographic expansion
      could be dated to approximately 8,000 years before present with a 95% confidence
      interval of 10,000 to 3,000 years before present. CONCLUSIONS: This period
      coincides with the Neolithic expansion in the Western Mediterranean, suggesting a
      role of these settlers as vectors. Our findings thus propose that non
      domesticated animals and plants may give hints on the direction and timing of
      early human expansion routes.

PMID- 21731623
TI  - Typing late prehistoric cows and bulls--osteology and genetics of cattle at the
      Eketorp ringfort on the Oland island in Sweden.
AB  - Human management of livestock and the presence of different breeds have been
      discussed in archaeozoology and animal breeding. Traditionally osteometrics has
      been the main tool in addressing these questions. We combine osteometrics with
      molecular sex identifications of 104 of 340 morphometrically analysed bones in
      order to investigate the use of cattle at the Eketorp ringfort on the Oland
      island in Sweden. The fort is dated to 300-1220/50 A.D., revealing three
      different building phases. In order to investigate specific patterns and shifts
      through time in the use of cattle the genetic data is evaluated in relation to
      osteometric patterns and occurrence of pathologies on cattle metapodia. Males
      were genotyped for a Y-chromosomal SNP in UTY19 that separates the two major
      haplogroups, Y1 and Y2, in taurine cattle. A subset of the samples were also
      genotyped for one SNP involved in coat coloration (MC1R), one SNP putatively
      involved in resistance to cattle plague (TLR4), and one SNP in intron 5 of the
      IGF-1 gene that has been associated to size and reproduction.The results of the
      molecular analyses confirm that the skeletal assemblage from Eketorp is dominated
      by skeletal elements from females, which implies that dairying was important.
      Pathological lesions on the metapodia were classified into two groups; those
      associated with the use as draught animals and those lesions without a similar
      aetiology. The results show that while bulls both exhibit draught related lesions
      and other types of lesions, cows exhibit other types of lesions. Interestingly, a
      few elements from females exhibit draught related lesions. We conclude that this
      reflects the different use of adult female and male cattle.Although we note some
      variation in the use of cattle at Eketorp between Iron Age and Medieval time we
      have found little evidence for the use of different types of animals for specific
      purposes. The use of specific (genetic) breeds seems to be a phenomenon that
      developed later than the Eketorp settlement.

PMID- 21731624
TI  - In vivo serial MR imaging of magnetically labeled endothelial progenitor cells
      homing to the endothelium injured artery in mice.
AB  - BACKGROUND: Emerging evidence of histopathological analyses suggests that
      endothelial progenitor cells (EPCs) play an important role in vascular diseases.
      Neointimal hyperplasia can be reduced by intravenous transfusion of EPCs after
      vascular injury in mice. Therefore, it would be advantageous to develop an in
      vivo technique that can explore the temporal and spatial migration of EPCs homing
      to the damaged endothelium noninvasively. METHODOLOGY/PRINCIPAL FINDINGS: The
      left carotid common artery (LCCA) was injured by removal of endothelium with a
      flexible wire in Kunming mice. EPCs were collected by in vitro culture of spleen
      derived mouse mononuclear cells (MNCs). EPCs labeling was carried out in vitro
      using Fe2O3-poly-L-lysine (Fe2O3-PLL). In vivo serial MR imaging was performed to
      follow-up the injured artery at different time points after intravenous
      transfusion of EPCs. Vessel wall areas of injured artery were computed on T2WI.
      Larger MR signal voids of vessel wall on T2WI was revealed in all 6 mice of the
      labeled EPC transfusion group 15 days after LCCA injury, and it was found only in
      1 mouse in the unlabeled EPC transfusion group (p = 0.015). Quantitative analyses
      of vessel wall areas on T2WI showed that the vessel wall areas of labeled EPC
      transfusion group were less than those of unlabeled EPC transfusion group and
      control group fifteen days after artery injury (p<0.05). Histopathological
      analyses confirmed accumulation and distribution of transfused EPCs at the injury
      site of LCCA. CONCLUSIONS/SIGNIFICANCE: These data indicate that MR imaging might
      be used as an in vivo method for the tracking of EPCs homing to the endothelium
      injured artery.

PMID- 21731625
TI  - An in vitro model of the glomerular capillary wall using electrospun collagen
      nanofibres in a bioartificial composite basement membrane.
AB  - The filtering unit of the kidney, the glomerulus, contains capillaries whose
      walls function as a biological sieve, the glomerular filtration barrier. This
      comprises layers of two specialised cells, glomerular endothelial cells (GEnC)
      and podocytes, separated by a basement membrane. Glomerular filtration barrier
      function, and dysfunction in disease, remains incompletely understood, partly due
      to difficulties in studying the relevant cell types in vitro. We have addressed
      this by generation of unique conditionally immortalised human GEnC and podocytes.
      However, because the glomerular filtration barrier functions as a whole, it is
      necessary to develop three dimensional co-culture models to maximise the benefit
      of the availability of these cells. Here we have developed the first two tri
      layer models of the glomerular capillary wall. The first is based on tissue
      culture inserts and provides evidence of cell-cell interaction via soluble
      mediators. In the second model the synthetic support of the tissue culture insert
      is replaced with a novel composite bioartificial membrane. This consists of a
      nanofibre membrane containing collagen I, electrospun directly onto a micro
      photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in
      monolayers on either side of the insert support or the novel membrane to form a
      tri-layer model recapitulating the human glomerular capillary in vitro. These
      models will advance the study of both the physiology of normal glomerular
      filtration and of its disruption in glomerular disease.

PMID- 21731626
TI  - New insights into the evolution of Wolbachia infections in filarial nematodes
      inferred from a large range of screened species.
AB  - BACKGROUND: Wolbachia are intriguing symbiotic endobacteria with a peculiar host
      range that includes arthropods and a single nematode family, the Onchocercidae
      encompassing agents of filariases. This raises the question of the origin of
      infection in filariae. Wolbachia infect the female germline and the hypodermis.
      Some evidences lead to the theory that Wolbachia act as mutualist and coevolved
      with filariae from one infection event: their removal sterilizes female filariae;
      all the specimens of a positive species are infected; Wolbachia are vertically
      inherited; a few species lost the symbiont. However, most data on Wolbachia and
      filaria relationships derive from studies on few species of Onchocercinae and
      Dirofilariinae, from mammals. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the
      Wolbachia distribution testing 35 filarial species, including 28 species and 7
      genera and/or subgenera newly screened, using PCR, immunohistochemical staining,
      whole mount fluorescent analysis, and cocladogenesis analysis. (i) Among the
      newly screened Onchocercinae from mammals eight species harbour Wolbachia but for
      some of them, bacteria are absent in the hypodermis, or in variable density. (ii)
      Wolbachia are not detected in the pathological model Monanema martini and in 8,
      upon 9, species of Cercopithifilaria. (iii) Supergroup F Wolbachia is identified
      in two newly screened Mansonella species and in Cercopithifilaria japonica. (iv)
      Type F Wolbachia infect the intestinal cells and somatic female genital tract.
      (v) Among Oswaldofilariinae, Waltonellinae and Splendidofilariinae, from saurian,
      anuran and bird respectively, Wolbachia are not detected.
      CONCLUSIONS/SIGNIFICANCE: The absence of Wolbachia in 63% of onchocercids,
      notably in the ancestral Oswaldofilariinae estimated 140 mya old, the diverse
      tissues or specimens distribution, and a recent lateral transfer in supergroup F
      Wolbachia, modify the current view on the role and evolution of the endosymbiont
      and their hosts. Further genomic analyses on some of the newly sampled species
      are welcomed to decipher the open questions.

PMID- 21731627
TI  - Fortune favours the bold: an agent-based model reveals adaptive advantages of
      overconfidence in war.
AB  - Overconfidence has long been considered a cause of war. Like other decision
      making biases, overconfidence seems detrimental because it increases the
      frequency and costs of fighting. However, evolutionary biologists have proposed
      that overconfidence may also confer adaptive advantages: increasing ambition,
      resolve, persistence, bluffing opponents, and winning net payoffs from risky
      opportunities despite occasional failures. We report the results of an agent
      based model of inter-state conflict, which allows us to evaluate the performance
      of different strategies in competition with each other. Counter-intuitively, we
      find that overconfident states predominate in the population at the expense of
      unbiased or underconfident states. Overconfident states win because: (1) they are
      more likely to accumulate resources from frequent attempts at conquest; (2) they
      are more likely to gang up on weak states, forcing victims to split their
      defences; and (3) when the decision threshold for attacking requires an
      overwhelming asymmetry of power, unbiased and underconfident states shirk many
      conflicts they are actually likely to win. These "adaptive advantages" of
      overconfidence may, via selection effects, learning, or evolved psychology, have
      spread and become entrenched among modern states, organizations and decision
      makers. This would help to explain the frequent association of overconfidence and
      war, even if it no longer brings benefits today.

PMID- 21731628
TI  - Chronic losartan administration reduces mortality and preserves cardiac but not
      skeletal muscle function in dystrophic mice.
AB  - Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal
      and cardiac muscle for which there is no effective therapy. Angiotension receptor
      blockade (ARB) has excellent therapeutic potential in DMD based on recent data
      demonstrating attenuation of skeletal muscle disease progression during 6-9
      months of therapy in the mdx mouse model of DMD. Since cardiac-related death is
      major cause of mortality in DMD, it is important to evaluate the effect of any
      novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB
      on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice
      received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for
      two years, after which echocardiography was performed to assess cardiac function.
      Skeletal muscle weight, morphology, and function were assessed. Fibrosis was
      evaluated in the diaphragm and heart by Trichrome stain and by determination of
      tissue hydroxyproline content. By the study endpoint, 88% of treated mice were
      alive compared to only 44% of untreated (p = 0.05). No difference in skeletal
      muscle morphology, function, or fibrosis was noted in losartan-treated animals.
      Cardiac function was significantly preserved with losartan treatment, with a
      trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal
      muscle disease progression, suggesting that other pathways that trigger fibrosis
      dominate over angiotensin II in skeletal muscle long term, unlike the situation
      in the heart. Our study suggests that ARB may be an important prophylactic
      treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle
      disease.

PMID- 21731629
TI  - Identification of the allosteric regulatory site of insulysin.
AB  - BACKGROUND: Insulin degrading enzyme (IDE) is responsible for the metabolism of
      insulin and plays a role in clearance of the Abeta peptide associated with
      Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four
      structurally related domains and exists primarily as a dimer, exhibits allosteric
      kinetics, being activated by both small substrate peptides and polyphosphates
      such as ATP. PRINCIPAL FINDINGS: The crystal structure of a catalytically
      compromised mutant of IDE has electron density for peptide ligands bound at the
      active site in domain 1 and a distal site in domain 2. Mutating residues in the
      distal site eliminates allosteric kinetics and activation by a small peptide, as
      well as greatly reducing activation by ATP, demonstrating that this site plays a
      key role in allostery. Comparison of the peptide bound IDE structure (using a low
      activity E111F IDE mutant) with unliganded wild type IDE shows a change in the
      interface between two halves of the clamshell-like molecule, which may enhance
      enzyme activity by altering the equilibrium between closed and open
      conformations. In addition, changes in the dimer interface suggest a basis for
      communication between subunits. CONCLUSIONS/SIGNIFICANCE: Our findings indicate
      that a region remote from the active site mediates allosteric activation of
      insulysin by peptides. Activation may involve a small conformational change that
      weakens the interface between two halves of the enzyme.

PMID- 21731630
TI  - Content disputes in Wikipedia reflect geopolitical instability.
AB  - Indicators that rank countries according socioeconomic measurements are important
      tools for regional development and political reform. Those currently in
      widespread use are sometimes criticized for a lack of reproducibility or the
      inability to compare values over time, necessitating simple, fast and systematic
      measures. Here, we applied the 'guilt by association' principle often used in
      biological networks to the information network within the online encyclopedia
      Wikipedia to create an indicator quantifying the degree to which pages linked to
      a country are disputed by contributors. The indicator correlates with metrics of
      governance, political or economic stability about as well as they correlate with
      each other, and though faster and simpler, it is remarkably stable over time
      despite constant changes in the underlying disputes. For some countries, changes
      over a four year period appear to correlate with world events related to
      conflicts or economic problems.

PMID- 21731632
TI  - Neuroanatomical correlates of suicide in psychosis: the possible role of von
      Economo neurons.
AB  - Suicide is the most important incident in psychiatric disorders. Psychological
      pain and empathy to pain involves a neural network that involves the anterior
      cingulate cortex (ACC) and the anterior insula (AI). At the neuronal level,
      little is known about how complex emotions such as shame, guilt, self-derogation
      and social isolation, all of which feature suicidal behavior, are represented in
      the brain. Based on the observation that the ACC and the AI contain a large
      spindle-shaped cell type, referred to as von Economo neuron (VEN), which has
      dramatically increased in density during human evolution, and on growing evidence
      that VENs play a role in the pathophysiology of various neuropsychiatric
      disorders, including autism, psychosis and dementia, we examined the density of
      VENs in the ACC of suicide victims. The density of VENs was determined using
      cresyl violet-stained sections of the ACC of 39 individuals with psychosis (20
      cases with schizophrenia, 19 with bipolar disorder). Nine subjects had died from
      suicide. Twenty specimen were available from the right, 19 from the left ACC. The
      density of VENs was significantly greater in the ACC of suicide victims with
      psychotic disorders compared with psychotic individuals who died from other
      causes. This effect was restricted to the right ACC. VEN density in the ACC seems
      to be increased in suicide victims with psychosis. This finding may support the
      assumption that VEN have a special role in emotion processing and self
      evaluation, including negative self-appraisal.

PMID- 21731631
TI  - The cycad genotoxin MAM modulates brain cellular pathways involved in
      neurodegenerative disease and cancer in a DNA damage-linked manner.
AB  - Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside
      cycasin, induces genetic alterations in bacteria, yeast, plants, insects and
      mammalian cells, but adult nerve cells are thought to be unaffected. We show that
      the brains of adult C57BL6 wild-type mice treated with a single systemic dose of
      MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that
      remains constant up to 7 days post-treatment. By contrast, MAM-treated mice
      lacking a functional gene encoding the DNA repair enzyme O6-mG DNA
      methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours
      post-treatment. The DNA damage was linked to changes in the expression of genes
      in cell-signaling pathways associated with cancer, human neurodegenerative
      disease, and neurodevelopmental disorders. These data are consistent with the
      established developmental neurotoxic and carcinogenic properties of MAM in
      rodents. They also support the hypothesis that early-life exposure to MAM
      glucoside (cycasin) has an etiological association with a declining, prototypical
      neurodegenerative disease seen in Guam, Japan, and New Guinea populations that
      formerly used the neurotoxic cycad plant for food or medicine, or both. These
      findings suggest environmental genotoxins, specifically MAM, target common
      pathways involved in neurodegeneration and cancer, the outcome depending on
      whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM
      related environmental genotoxins may have relevance to the etiology of related
      tauopathies, notably, Alzheimer's disease.

PMID- 21731633
TI  - Simvastatin prevents dopaminergic neurodegeneration in experimental parkinsonian
      models: the association with anti-inflammatory responses.
AB  - BACKGROUND: In addition to their original applications to lowering cholesterol,
      statins display multiple neuroprotective effects. N-methyl-D-aspartate (NMDA)
      receptors interact closely with the dopaminergic system and are strongly
      implicated in therapeutic paradigms of Parkinson's disease (PD). This study aims
      to investigate how simvastatin impacts on experimental parkinsonian models via
      regulating NMDA receptors. METHODOLOGY/PRINCIPAL FINDINGS: Regional changes in
      NMDA receptors in the rat brain and anxiolytic-like activity were examined after
      unilateral medial forebrain bundle lesion by 6-hydroxydopamine via a 3-week
      administration of simvastatin. NMDA receptor alterations in the post-mortem rat
      brain were detected by [3H]MK-801(Dizocilpine) binding autoradiography. 6
      hydroxydopamine treated PC12 was applied to investigate the neuroprotection of
      simvastatin, the association with NMDA receptors, and the anti-inflammation. 6
      hydroxydopamine induced anxiety and the downregulation of NMDA receptors in the
      hippocampus, CA1(Cornu Ammonis 1 Area), amygdala and caudate putamen was observed
      in 6-OHDA(6-hydroxydopamine) lesioned rats whereas simvastatin significantly
      ameliorated the anxiety-like activity and restored the expression of NMDA
      receptors in examined brain regions. Significant positive correlations were
      identified between anxiolytic-like activity and the restoration of expression of
      NMDA receptors in the hippocampus, amygdala and CA1 following simvastatin
      administration. Simvastatin exerted neuroprotection in 6-hydroxydopamine-lesioned
      rat brain and 6-hydroxydopamine treated PC12, partially by regulating NMDA
      receptors, MMP9 (matrix metalloproteinase-9), and TNF-a (tumour necrosis factor
      alpha). CONCLUSIONS/SIGNIFICANCE: Our results provide strong evidence that NMDA
      receptor modulation after simvastatin treatment could partially explain its
      anxiolytic-like activity and anti-inflammatory mechanisms in experimental
      parkinsonian models. These findings contribute to a better understanding of the
      critical roles of simvastatin in treating PD via NMDA receptors.

PMID- 21731634
TI  - The Smc5-Smc6 complex is required to remove chromosome junctions in meiosis.
AB  - Meiosis, a specialized cell division with a single cycle of DNA replication round
      and two consecutive rounds of nuclear segregation, allows for the exchange of
      genetic material between parental chromosomes and the formation of haploid
      gametes. The structural maintenance of chromosome (SMC) proteins aid manipulation
      of chromosome structures inside cells. Eukaryotic SMC complexes include cohesin,
      condensin and the Smc5-Smc6 complex. Meiotic roles have been discovered for
      cohesin and condensin. However, although Smc5-Smc6 is known to be required for
      successful meiotic divisions, the meiotic functions of the complex are not well
      understood. Here we show that the Smc5-Smc6 complex localizes to specific
      chromosome regions during meiotic prophase I. We report that meiotic cells
      lacking Smc5-Smc6 undergo catastrophic meiotic divisions as a consequence of
      unresolved linkages between chromosomes. Surprisingly, meiotic segregation
      defects are not rescued by abrogation of Spo11-induced meiotic recombination,
      indicating that at least some chromosome linkages in smc5-smc6 mutants originate
      from other cellular processes. These results demonstrate that, as in mitosis,
      Smc5-Smc6 is required to ensure proper chromosome segregation during meiosis by
      preventing aberrant recombination intermediates between homologous chromosomes.

PMID- 21731635
TI  - What the 'Moonwalk' illusion reveals about the perception of relative depth from
      motion.
AB  - When one visual object moves behind another, the object farther from the viewer
      is progressively occluded and/or disoccluded by the nearer object. For nearly
      half a century, this dynamic occlusion cue has been thought to be sufficient by
      itself for determining the relative depth of the two objects. This view is
      consistent with the self-evident geometric fact that the surface undergoing
      dynamic occlusion is always farther from the viewer than the occluding surface.
      Here we use a contextual manipulation ofa previously known motion illusion, which
      we refer to as the'Moonwalk' illusion, to demonstrate that the visual system
      cannot determine relative depth from dynamic occlusion alone. Indeed, in the
      Moonwalk illusion, human observers perceive a relative depth contrary to the
      dynamic occlusion cue. However, the perception of the expected relative depth is
      restored by contextual manipulations unrelated to dynamic occlusion. On the other
      hand, we show that an Ideal Observer can determine using dynamic occlusion alone
      in the same Moonwalk stimuli, indicating that the dynamic occlusion cue is, in
      principle, sufficient for determining relative depth. Our results indicate that
      in order to correctly perceive relative depth from dynamic occlusion, the human
      brain, unlike the Ideal Observer, needs additional segmentation information that
      delineate the occluder from the occluded object. Thus, neural mechanisms of
      object segmentation must, in addition to motion mechanisms that extract
      information about relative depth, play a crucial role in the perception of
      relative depth from motion.

PMID- 21731636
TI  - Raiders of the lost bark: orangutan foraging strategies in a degraded landscape.
AB  - Deforestation is rapidly transforming primary forests across the tropics into
      human-dominated landscapes. Consequently, conservationists need to understand how
      different taxa respond and adapt to these changes in order to develop appropriate
      management strategies. Our two year study seeks to determine how wild Sumatran
      orangutans (Pongo abelii) adapt to living in an isolated agroforest landscape by
      investigating the sex of crop-raiders related to population demographics, and
      their temporal variations in feeding behaviour and dietary composition. From
      focal animal sampling we found that nine identified females raided cultivated
      fruits more than the four males. Seasonal adaptations were shown through
      orangutan feeding habits that shifted from being predominantly fruit-based (56%
      of the total feeding time, then 22% on bark) to the fallback food of bark (44%,
      then 35% on fruits), when key cultivated resources such as jackfruit (Artocarpus
      integer), were unavailable. Cultivated fruits were mostly consumed in the
      afternoon and evening, when farmers had returned home. The finding that females
      take greater crop-raiding risks than males differs from previous human-primate
      conflict studies, probably because of the low risks associated (as farmers rarely
      retaliated) and low intraspecific competition between males. Thus, the behavioral
      ecology of orangutans living in this human-dominated landscape differs markedly
      from that in primary forest, where orangutans have a strictly wild food diet,
      even where primary rainforests directly borders farmland. The importance of wild
      food availability was clearly illustrated in this study with 21% of the total
      orangutan feeding time being allocated to feeding on cultivated fruits. As
      forests are increasingly converted to cultivation, humans and orangutans are
      predicted to come into conflict more frequently. This study reveals orangutan
      adaptations for coexisting with humans, e.g. changes in temporal foraging
      patterns, which should be used for guiding the development of specific human
      wildlife conflict mitigation strategies to lessen future crop-raiding and
      conflicts.

PMID- 21731637
TI  - Hybrid shell engineering of animal cells for immune protections and regulation of
      drug delivery: towards the design of "artificial organs".
AB  - BACKGROUND: With the progress in medicine, the average human life expectancy is
      continuously increasing. At the same time, the number of patients who require
      full organ transplantations is augmenting. Consequently, new strategies for cell
      transplantation are the subject of great interest. METHODOLOGY/PRINCIPAL
      FINDINGS: This work reports the design, the synthesis and the characterisation of
      robust and biocompatible mineralised beads composed of two layers: an alginate
      silica composite core and a Ca-alginate layer. The adequate choice of materials
      was achieved through cytotoxicity LDH release measurement and in vitro
      inflammatory assay (IL-8) to meet the biocompatibility requirements for medical
      purpose. The results obtained following this strategy provide a direct proof of
      the total innocuity of silica and alginate networks for human cells as
      underscored by the non-activation of immune defenders (THP-1 monocytes). The
      accessible pore size diameter of the mineralised beads synthesized was estimated
      between 22 and 30 nm, as required for efficient immuno-isolation without
      preventing the diffusion of nutrients and metabolites. The model human cells,
      HepG2, entrapped within these hybrid beads display a high survival rate over more
      than six weeks according to the measurements of intracellular enzymatic activity,
      respiration rate, as well as the "de novo" biosynthesis and secretion of albumin
      out of the beads. CONCLUSIONS/SIGNIFICANCE: The current study shows that active
      mammalian cells can be protected by a silica-alginate hybrid shell-like system.
      The functionality of the cell strain can be maintained. Consequently, cells
      coated with an artificial and a biocompatible mineral shell could respond
      physiologically within the human body in order to deliver therapeutic agents in a
      controlled fashion (i.e. insulin), substituting the declining organ functions of
      the patient.

PMID- 21731638
TI  - Adaptive evolution of the venom-targeted vWF protein in opossums that eat
      pitvipers.
AB  - The rapid evolution of venom toxin genes is often explained as the result of a
      biochemical arms race between venomous animals and their prey. However, it is not
      clear that an arms race analogy is appropriate in this context because there is
      no published evidence for rapid evolution in genes that might confer toxin
      resistance among routinely envenomed species. Here we report such evidence from
      an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae)
      and pitvipers (Serpentes: Crotalinae). In particular, we found high ratios of
      replacement to silent substitutions in the gene encoding von Willebrand Factor
      (vWF), a venom-targeted hemostatic blood protein, in a clade of opossums known to
      eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid
      substitutions in venom-resistant opossums include changes in net charge and
      hydrophobicity that are hypothesized to weaken the bond between vWF and one of
      its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our
      results provide the first example of rapid adaptive evolution in any venom
      targeted molecule, and they support the notion that an evolutionary arms race
      might be driving the rapid evolution of snake venoms. However, in the arms race
      implied by our results, venomous snakes are prey, and their venom has a
      correspondingly defensive function in addition to its usual trophic role.

PMID- 21731639
TI  - The complete genome sequence of Mycoplasma bovis strain Hubei-1.
AB  - Infection by Mycoplasma bovis (M. bovis) can induce diseases, such as pneumonia
      and otitis media in young calves and mastitis and arthritis in older animals.
      Here, we report the finished and annotated genome sequence of M. bovis strain
      Hubei-1, a strain isolated in 2008 that caused calf pneumonia on a Chinese farm.
      The genome of M. bovis strain Hubei-1 contains a single circular chromosome of
      953,114 bp with a 29.37% GC content. We identified 803 open reading frames (ORFs)
      that occupy 89.5% of the genome. While 34 ORFs were Hubei-1 specific, 662 ORFs
      had orthologs in the M. bovis type strain PG45 genome. Genome analysis validated
      lateral gene transfer between M. bovis and the Mycoplasma mycoides subspecies
      mycoides, while phylogenetic analysis found that the closest M. bovis neighbor is
      Mycoplasma agalactiae. Glycerol may be the main carbon and energy source of M.
      bovis, and most of the biosynthesis pathways were incomplete. We report that 47
      lipoproteins, 12 extracellular proteins and 18 transmembrane proteins are phase
      variable and may help M. bovis escape the immune response. Besides lipoproteins
      and phase-variable proteins, genomic analysis found two possible pathogenicity
      islands, which consist of four genes and 11 genes each, and several other
      virulence factors including hemolysin, lipoate protein ligase, dihydrolipoamide
      dehydrogenase, extracellular cysteine protease and 5'-nucleotidase.

PMID- 21731640
TI  - Spatial heterogeneity in resource distribution promotes facultative sociality in
      two trans-Saharan migratory birds.
AB  - BACKGROUND: Migrant populations must cope not only with environmental changes in
      different biomes, but also with the continuous constraints imposed by human
      induced changes through landscape transformation and resource patchiness.
      Theoretical studies suggest that changes in food distribution can promote changes
      in the social arrangement of individuals without apparent adaptive value.
      Empirical research on this subject has only been performed at reduced
      geographical scales and/or for single species. However, the relative contribution
      of food patchiness and predictability, both in space and time, to abundance and
      sociality can vary among species, depending on their degree of flexibility.
      METHODOLOGY/PRINCIPAL FINDINGS: By means of constrained zero-inflated Generalized
      Additive Models we analysed the spatial distribution of two trans-Saharan avian
      scavengers that breed (Europe) and winter (Africa) sympatrically, in relation to
      food availability. In the summering grounds, the probability of finding large
      numbers of both species increases close to predictable feeding sources, whereas
      in the wintering grounds, where food resources are widespread, we did not find
      such aggregation patterns, except for the black kite, which aggregated at desert
      locust outbreaks. The comparison of diets in both species through stable isotopes
      revealed that their diets overlapped during summering, but not during wintering.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that bird sociality at feeding
      grounds is closely linked to the pattern of spatial distribution and
      predictability of trophic resources, which are ultimately induced by human
      activities. Migrant species can show adaptive foraging strategies to face
      changing distribution of food availability in both wintering and summering
      quarters. Understanding these effects is a key aspect for predicting the fitness
      costs and population consequences of habitat transformations on the viability of
      endangered migratory species.

PMID- 21731641
TI  - Expression and trans-specific polymorphism of self-incompatibility RNases in
      coffea (Rubiaceae).
AB  - Self-incompatibility (SI) is widespread in the angiosperms, but identifying the
      biochemical components of SI mechanisms has proven to be difficult in most
      lineages. Coffea (coffee; Rubiaceae) is a genus of old-world tropical understory
      trees in which the vast majority of diploid species utilize a mechanism of
      gametophytic self-incompatibility (GSI). The S-RNase GSI system was one of the
      first SI mechanisms to be biochemically characterized, and likely represents the
      ancestral Eudicot condition as evidenced by its functional characterization in
      both asterid (Solanaceae, Plantaginaceae) and rosid (Rosaceae) lineages. The S
      RNase GSI mechanism employs the activity of class III RNase T2 proteins to
      terminate the growth of "self" pollen tubes. Here, we investigate the mechanism
      of Coffea GSI and specifically examine the potential for homology to S-RNase GSI
      by sequencing class III RNase T2 genes in populations of 14 African and
      Madagascan Coffea species and the closely related self-compatible species
      Psilanthus ebracteolatus. Phylogenetic analyses of these sequences aligned to a
      diverse sample of plant RNase T2 genes show that the Coffea genome contains at
      least three class III RNase T2 genes. Patterns of tissue-specific gene expression
      identify one of these RNase T2 genes as the putative Coffea S-RNase gene. We show
      that populations of SI Coffea are remarkably polymorphic for putative S-RNase
      alleles, and exhibit a persistent pattern of trans-specific polymorphism
      characteristic of all S-RNase genes previously isolated from GSI Eudicot
      lineages. We thus conclude that Coffea GSI is most likely homologous to the
      classic Eudicot S-RNase system, which was retained since the divergence of the
      Rubiaceae lineage from an ancient SI Eudicot ancestor, nearly 90 million years
      ago.

PMID- 21731642
TI  - Poly (A)+ transcriptome assessment of ERBB2-induced alterations in breast cell
      lines.
AB  - We report the first quantitative and qualitative analysis of the poly (A)+
      transcriptome of two human mammary cell lines, differentially expressing (human
      epidermal growth factor receptor) an oncogene over-expressed in approximately 25%
      of human breast tumors. Full-length cDNA populations from the two cell lines were
      digested enzymatically, individually tagged according to a customized method for
      library construction, and simultaneously sequenced by the use of the Titanium 454
      Roche-platform. Comprehensive bioinformatics analysis followed by experimental
      validation confirmed novel genes, splicing variants, single nucleotide
      polymorphisms, and gene fusions indicated by RNA-seq data from both samples.
      Moreover, comparative analysis showed enrichment in alternative events,
      especially in the exon usage category, in ERBB2 over-expressing cells, data
      indicating regulation of alternative splicing mediated by the oncogene.
      Alterations in expression levels of genes, such as LOX, ATP5L, GALNT3, and MME
      revealed by large-scale sequencing were confirmed between cell lines as well as
      in tumor specimens with different ERBB2 backgrounds. This approach was shown to
      be suitable for structural, quantitative, and qualitative assessment of complex
      transcriptomes and revealed new events mediated by ERBB2 overexpression, in
      addition to potential molecular targets for breast cancer that are driven by this
      oncogene.

PMID- 21731643
TI  - The NS1 glycoprotein can generate dramatic antibody-enhanced dengue viral
      replication in normal out-bred mice resulting in lethal multi-organ disease.
AB  - Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and
      production of antibody-enhanced disease (AED) was tested in out-bred mice.
      Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1)
      glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains reacted
      strongly and weakly with these antigens, respectively. These PAbs contained the
      IgG2a subclass, which cross-reacted with the virion-associated envelope (E)
      glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its
      AER via all mouse Fcgamma-receptor classes. Indeed, when these mice were
      challenged with a low dose (<0.5 LD50) of the DENV-2 NSx strain, but not the NG-C
      strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice
      developed life-threatening acute respiratory distress syndrome (ARDS), displayed
      by diffuse alveolar damage (DAD) resulting from i) dramatic interstitial alveolar
      septa-thickening with mononuclear cells, ii) some hyperplasia of alveolar type-II
      pneumocytes, iii) copious intra-alveolar protein secretion, iv) some hyaline
      membrane-covered alveolar walls, and v) DENV-2 antigen-positive alveolar
      macrophages. These mice also developed meningo-encephalitis, with greater than
      90,000-fold DENV-2 AER titers in microglial cells located throughout their brain
      parenchyma, some of which formed nodules around dead neurons. Their spleens
      contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp
      macrophages, while their livers displayed extensive necrosis, apoptosis and macro
      and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes.
      Their infections were confirmed by DENV-2 isolations from their lungs, spleens
      and livers. These findings accord with those reported in fatal human "severe
      dengue" cases. This DENV-2 AER/AED was blocked by high concentrations of only the
      NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1
      glycoprotein-based vaccines, particularly against DENV strains that contain
      multiple mutations or genetic recombination within or between their DENV E and
      NS1 glycoprotein-encoding genes. The model provides potential for assessing DENV
      strain pathogenicity and anti-DENV therapies in normal mice.

PMID- 21731644
TI  - Improved phylogenetic analyses corroborate a plausible position of Martialis
      heureka in the ant tree of life.
AB  - Martialinae are pale, eyeless and probably hypogaeic predatory ants.
      Morphological character sets suggest a close relationship to the ant subfamily
      Leptanillinae. Recent analyses based on molecular sequence data suggest that
      Martialinae are the sister group to all extant ants. However, by comparing
      molecular studies and different reconstruction methods, the position of
      Martialinae remains ambiguous. While this sister group relationship was well
      supported by Bayesian partitioned analyses, Maximum Likelihood approaches could
      not unequivocally resolve the position of Martialinae. By re-analysing a previous
      published molecular data set, we show that the Maximum Likelihood approach is
      highly appropriate to resolve deep ant relationships, especially between
      Leptanillinae, Martialinae and the remaining ant subfamilies. Based on improved
      alignments, alignment masking, and tree reconstructions with a sufficient number
      of bootstrap replicates, our results strongly reject a placement of Martialinae
      at the first split within the ant tree of life. Instead, we suggest that
      Leptanillinae are a sister group to all other extant ant subfamilies, whereas
      Martialinae branch off as a second lineage. This assumption is backed by
      approximately unbiased (AU) tests, additional Bayesian analyses and split
      networks. Our results demonstrate clear effects of improved alignment approaches,
      alignment masking and data partitioning. We hope that our study illustrates the
      importance of thorough, comprehensible phylogenetic analyses using the example of
      ant relationships.

PMID- 21731645
TI  - Region-specific responses of adductor longus muscle to gravitational load
      dependent activity in Wistar Hannover rats.
AB  - Response of adductor longus (AL) muscle to gravitational unloading and reloading
      was studied. Male Wistar Hannover rats (5-wk old) were hindlimb-unloaded for 16
      days with or without 16-day ambulation recovery. The electromyogram (EMG)
      activity in AL decreased after acute unloading, but that in the rostral region
      was even elevated during continuous unloading. The EMG levels in the caudal
      region gradually increased up to 6th day, but decreased again. Approximately 97%
      of fibers in the caudal region were pure type I at the beginning of experiment.
      Mean percentage of type I fibers in the rostral region was 61% and that of type
      I+II and II fiber was 14 and 25%, respectively. The percent type I fibers
      decreased and de novo appearance of type I+II was noted after unloading. But the
      fiber phenotype in caudal, not rostral and middle, region was normalized after 16
      day ambulation. Pronounced atrophy after unloading and re-growth following
      ambulation was noted in type I fibers of the caudal region. Sarcomere length in
      the caudal region was passively shortened during unloading, but that in the
      rostral region was unchanged or even stretched slightly. Growth-associated
      increase of myonuclear number seen in the caudal region of control rats was
      inhibited by unloading. Number of mitotic active satellite cells decreased after
      unloading only in the caudal region. It was indicated that the responses of fiber
      properties in AL to unloading and reloading were closely related to the region
      specific neural and mechanical activities, being the caudal region more
      responsive.

PMID- 21731646
TI  - Long-term costs and health impact of continued global fund support for
      antiretroviral therapy.
AB  - BACKGROUND: By the end of 2011 Global Fund investments will be supporting 3.5
      million people on antiretroviral therapy (ART) in 104 low- and middle-income
      countries. We estimated the cost and health impact of continuing treatment for
      these patients through 2020. METHODS AND FINDINGS: Survival on first-line and
      second-line ART regimens is estimated based on annual retention rates reported by
      national AIDS programs. Costs per patient-year were calculated from country
      reported ARV procurement prices, and expenditures on laboratory tests, health
      care utilization and end-of-life care from in-depth costing studies. Of the 3.5
      million ART patients in 2011, 2.3 million will still need treatment in 2020. The
      annual cost of maintaining ART falls from $1.9 billion in 2011 to $1.7 billion in
      2020, as a result of a declining number of surviving patients partially offset by
      increasing costs as more patients migrate to second-line therapy. The Global Fund
      is expected to continue being a major contributor to meeting this financial need,
      alongside other international funders and domestic resources. Costs would be $150
      million less in 2020 with an annual 5% decline in first-line ARV prices and $150
      370 million less with a 5%-12% annual decline in second-line prices, but $200
      million higher in 2020 with phase out of stavudine (d4T), or $200 million higher
      with increased migration to second-line regimens expected if all countries
      routinely adopted viral load monitoring. Deaths postponed by ART correspond to
      830,000 life-years saved in 2011, increasing to around 2.3 million life-years
      every year between 2015 and 2020. CONCLUSIONS: Annual patient-level direct costs
      of supporting a patient cohort remain fairly stable over 2011-2020, if current
      antiretroviral prices and delivery costs are maintained. Second-line
      antiretroviral prices are a major cost driver, underscoring the importance of
      investing in treatment quality to improve retention on first-line regimens.

PMID- 21731647
TI  - Changes in body condition of hibernating bats support the thrifty female
      hypothesis and predict consequences for populations with white-nose syndrome.
AB  - White-nose syndrome (WNS) is a new disease of bats that has devastated
      populations in eastern North America. Infection with the fungus, Geomyces
      destructans, is thought to increase the time bats spend out of torpor during
      hibernation, leading to starvation. Little is known about hibernation in healthy,
      free-ranging bats and more data are needed to help predict consequences of WNS.
      Trade-offs presumably exist between the energetic benefits and
      physiological/ecological costs of torpor, leading to the prediction that the
      relative importance of spring energy reserves should affect an individual's use
      of torpor and depletion of energy reserves during winter. Myotis lucifugus mate
      during fall and winter but females do not become pregnant until after spring
      emergence. Thus, female reproductive success depends on spring fat reserves while
      male reproductive success does not. Consequently, females should be "thrifty" in
      their use of fat compared to males. We measured body condition index (BCI;
      mass/forearm length) of 432 M. lucifugus in Manitoba, Canada during the winter of
      2009/2010. Bats were captured during the fall mating period (n = 200), early
      hibernation (n = 125), and late hibernation (n = 128). Adult females entered
      hibernation with greater fat reserves and consumed those reserves more slowly
      than adult males and young of the year. Consequently, adult females may be more
      likely than males or young of the year to survive the disruption of energy
      balance associated with WNS, although surviving females may not have sufficient
      reserves to support reproduction.

PMID- 21731648
TI  - The p53 tumor suppressor is stabilized by inhibitor of growth 1 (ING1) by
      blocking polyubiquitination.
AB  - The INhibitor of Growth tumor suppressors (ING1-ING5) affect aging, apoptosis,
      DNA repair and tumorigenesis. Plant homeodomains (PHD) of ING proteins bind
      histones in a methylation-sensitive manner to regulate chromatin structure. ING1
      and ING2 contain a polybasic region (PBR) adjacent to their PHDs that binds
      stress-inducible phosphatidylinositol monophosphate (PtIn-MP) signaling lipids to
      activate these INGs. ING1 induces apoptosis independently of p53 but other
      studies suggest proapoptotic interdependence of ING1 and p53 leaving their
      functional relationship unclear. Here we identify a novel ubiquitin-binding
      domain (UBD) that overlaps with the PBR of ING1 and shows similarity to
      previously described UBDs involved in DNA damage responses. The ING1 UBD binds
      ubiquitin with high affinity (K(d)~100 nM) and ubiquitin competes with PtIn-MPs
      for ING1 binding. ING1 expression stabilized wild-type, but not mutant p53 in an
      MDM2-independent manner and knockdown of endogenous ING1 depressed p53 levels in
      a transcription-independent manner. ING1 stabilized unmodified and six
      multimonoubiquitinated forms of wild-type p53 that were also seen upon DNA
      damage, but not p53 mutants lacking the six known sites of ubiquitination. We
      also find that ING1 physically interacts with herpesvirus-associated ubiquitin
      specific protease (HAUSP), a p53 and MDM2 deubiquitinase (DUB), and knockdown of
      HAUSP blocks the ability of ING1 to stabilize p53. These data link lipid stress
      signaling to ubiquitin-mediated proteasomal degradation through the PBR/UBD of
      ING1 and further indicate that ING1 stabilizes p53 by inhibiting
      polyubiquitination of multimonoubiquitinated forms via interaction with and
      colocalization of the HAUSP-deubiquitinase with p53.

PMID- 21731649
TI  - Seeing your error alters my pointing: observing systematic pointing errors
      induces sensori-motor after-effects.
AB  - During the procedure of prism adaptation, subjects execute pointing movements to
      visual targets under a lateral optical displacement: as consequence of the
      discrepancy between visual and proprioceptive inputs, their visuo-motor activity
      is characterized by pointing errors. The perception of such final errors triggers
      error-correction processes that eventually result into sensori-motor
      compensation, opposite to the prismatic displacement (i.e., after-effects). Here
      we tested whether the mere observation of erroneous pointing movements, similar
      to those executed during prism adaptation, is sufficient to produce adaptation
      like after-effects. Neurotypical participants observed, from a first-person
      perspective, the examiner's arm making incorrect pointing movements that
      systematically overshot visual targets location to the right, thus simulating a
      rightward optical deviation. Three classical after-effect measures
      (proprioceptive, visual and visual-proprioceptive shift) were recorded before and
      after first-person's perspective observation of pointing errors. Results showed
      that mere visual exposure to an arm that systematically points on the right-side
      of a target (i.e., without error correction) produces a leftward after-effect,
      which mostly affects the observer's proprioceptive estimation of her body
      midline. In addition, being exposed to such a constant visual error induced in
      the observer the illusion "to feel" the seen movement. These findings indicate
      that it is possible to elicit sensori-motor after-effects by mere observation of
      movement errors.

PMID- 21731650
TI  - A comprehensive survey of miRNA repertoire and 3' addition events in the
      placentas of patients with pre-eclampsia from high-throughput sequencing.
AB  - BACKGROUND: To gain insight into potential roles of isomiR spectrum and isomiRs
      with 3' additions in pre-eclampsia, we performed a comprehensive survey of miRNA
      repertoire and 3' addition events from placental samples with different degrees
      of pre-eclampsia by applying SOLiD sequencing platform. PRINCIPAL FINDINGS: Over
      30% isomiRs were detected with 3' non-template additional nucleotides, especially
      for additional nucleotide of adenosine. However, these modified isomiRs showed a
      lower percentage of total miRNA expression (<15%). Generally, 1-3 abundant
      isomiRs from a given miRNA locus were identified, but none of them was detected
      with 3' additions. Different miRNAs indicated various isomiR spectrums and
      expression patterns. The most abundant isomiR spectrum, isomiR profile and
      expression pattern always were stability, but herein we found several exceptions
      across samples, especially between normal and diseased samples. At isomiR level,
      we detected a distinct subset of differentially expressed modified isomiRs
      between normal and diseased samples or between mild and severe samples. Gene
      Ontology analysis of their experimentally validated target genes revealed
      enrichment for specific biological process categories. CONCLUSIONS: The
      phenomenon of multiple isomiRs, especially for isomiRs with 3' additions, is not
      a random event during pre-miRNA processing. Varieties of isomiRs and expression
      patterns reveal potential functional implication and should be taken into
      account. The study enriches association of miRNAs and human disease, including
      potential roles of various miRNA variants and 3' addition events.

PMID- 21731651
TI  - Carbon nanotubes enhance cytotoxicity mediated by human lymphocytes in vitro.
AB  - With the expansion of the potential applications of carbon nanotubes (CNT) in
      biomedical fields, the toxicity and biocompatibility of CNT have become issues of
      growing concern. Since the immune system often mediates tissue damage during
      pathogenesis, it is important to explore whether CNT can trigger cytotoxicity
      through affecting the immune functions. In the current study, we evaluated the
      influence of CNT on the cytotoxicity mediated by human lymphocytes in vitro. The
      results showed that while CNT at low concentrations (0.001 to 0.1 ug/ml) did not
      cause obvious cell death or apoptosis directly, it enhanced lymphocyte-mediated
      cytotoxicity against multiple human cell lines. In addition, CNT increased the
      secretion of IFN-gamma and TNF-alpha by the lymphocytes. CNT also upregulated the
      NF-kappaB expression in lymphocytes, and the blockage of the NF-kappaB pathway
      reduced the lymphocyte-mediated cytotoxicity triggered by CNT. These results
      suggest that CNT at lower concentrations may prospectively initiate an indirect
      cytotoxicity through affecting the function of lymphocytes.

PMID- 21731652
TI  - Apoptosis governs the elimination of Schistosoma japonicum from the non
      permissive host Microtus fortis.
AB  - The reed vole, Microtus fortis, is the only known mammalian host in which
      schistosomes of Schistosoma japonicum are unable to mature and cause significant
      pathogenesis. However, little is known about how Schistosoma japonicum maturation
      (and, therefore, the development of schistosomiasis) is prevented in M. fortis.
      In the present study, the ultrastructure of 10 days post infection schistosomula
      from BALB/c mice and M. fortis were first compared using scanning electron
      microscopy and transmission electron microscopy. Electron microscopic
      investigations showed growth retardation and ultrastructural differences in the
      tegument and sub-tegumental tissues as well as in the parenchymal cells of
      schistosomula from M. fortis compared with those in BALB/c mice. Then, microarray
      analysis revealed significant differential expression between the schistosomula
      from the two rodents, with 3,293 down-regulated (by >= 2-fold) and 71 up
      regulated (>= 2 fold) genes in schistosomula from the former. The up-regulated
      genes included a proliferation-related gene encoding granulin (Grn) and
      tropomyosin. Genes that were down-regulated in schistosomula from M. fortis
      included apoptosis-inhibited genes encoding a baculoviral IAP repeat-containing
      protein (SjIAP) and cytokine-induced apoptosis inhibitor (SjCIAP), genes encoding
      molecules involved in insulin metabolism, long-chain fatty acid metabolism,
      signal transduction, the transforming growth factor (TGF) pathway, the Wnt
      pathway and in development. TUNEL (terminal deoxynucleotidyl transferase dUTP
      nick end labeling) and PI/Annexin V-FITC assays, caspase 3/7 activity analysis,
      and flow cytometry revealed that the percentages of early apoptotic and late
      apoptotic and/or necrotic cells, as well as the level of caspase activity, in
      schistosomula from M. fortis were all significantly higher than in those from
      BALB/c mice.

PMID- 21731653
TI  - Apical transport of influenza A virus ribonucleoprotein requires Rab11-positive
      recycling endosome.
AB  - Influenza A virus RNA genome exists as eight-segmented ribonucleoprotein
      complexes containing viral RNA polymerase and nucleoprotein (vRNPs). Packaging of
      vRNPs and virus budding take place at the apical plasma membrane (APM). However,
      little is known about the molecular mechanisms of apical transport of newly
      synthesized vRNP. Transfection of fluorescent-labeled antibody and subsequent
      live cell imaging revealed that punctate vRNP signals moved along microtubules
      rapidly but intermittently in both directions, suggestive of vesicle trafficking.
      Using a series of Rab family protein, we demonstrated that progeny vRNP localized
      to recycling endosome (RE) in an active/GTP-bound Rab11-dependent manner. The
      vRNP interacted with Rab11 through viral RNA polymerase. The localization of vRNP
      to RE and subsequent accumulation to the APM were impaired by overexpression of
      Rab binding domains (RBD) of Rab11 family interacting proteins (Rab11-FIPs).
      Similarly, no APM accumulation was observed by overexpression of class II Rab11
      FIP mutants lacking RBD. These results suggest that the progeny vRNP makes use of
      Rab11-dependent RE machinery for APM trafficking.

PMID- 21731654
TI  - Relevant assay to study the adhesion of Plasmodium falciparum-infected
      erythrocytes to the placental epithelium.
AB  - In placental malaria, Plasmodium falciparum-infected erythrocytes adhere to the
      apical plasma membrane of the placental epithelium, triggering an impairment of
      placental function detrimental to the fetus. The design of anti-adhesion
      intervention strategies requires a detailed understanding of the mechanisms
      involved. However, most adhesion assays lack in vivo relevance and are hardly
      quantitative. Here, we describe a flow cytometry-based adhesion assay that is
      fully relevant by using apical epithelial plasma membrane vesicles as the
      adhesion matrix, and being applicable to infected erythrocytes directly isolated
      from patients. Adhesion is measured both as the percentage of pathogens bound to
      epithelial membrane vesicles as well as the mean number of vesicles bound per
      infected erythrocytes. We show that adhesins alternative to those currently
      identified could be involved. This demonstrates the power of this assay to
      advance our understanding of epithelial adhesion of infected erythrocytes and in
      the design of intervention strategies.

PMID- 21731655
TI  - Travelling waves of a delayed SIR epidemic model with nonlinear incidence rate
      and spatial diffusion.
AB  - This paper is concerned with the existence of travelling waves to a SIR epidemic
      model with nonlinear incidence rate, spatial diffusion and time delay. By
      analyzing the corresponding characteristic equations, the local stability of a
      disease-free steady state and an endemic steady state to this system under
      homogeneous Neumann boundary conditions is discussed. By using the cross
      iteration method and the Schauder's fixed point theorem, we reduce the existence
      of travelling waves to the existence of a pair of upper-lower solutions. By
      constructing a pair of upper-lower solutions, we derive the existence of a
      travelling wave connecting the disease-free steady state and the endemic steady
      state. Numerical simulations are carried out to illustrate the main results.

PMID- 21731656
TI  - Discovering disease associations by integrating electronic clinical data and
      medical literature.
AB  - Electronic health record (EHR) systems offer an exceptional opportunity for
      studying many diseases and their associated medical conditions within a
      population. The increasing number of clinical record entries that have become
      available electronically provides access to rich, large sets of patients'
      longitudinal medical information. By integrating and comparing relations found in
      the EHRs with those already reported in the literature, we are able to verify
      existing and to identify rare or novel associations. Of particular interest is
      the identification of rare disease co-morbidities, where the small numbers of
      diagnosed patients make robust statistical analysis difficult. Here, we introduce
      ADAMS, an Application for Discovering Disease Associations using Multiple
      Sources, which contains various statistical and language processing operations.
      We apply ADAMS to the New York-Presbyterian Hospital's EHR to combine the
      information from the relational diagnosis tables and textual discharge summaries
      with those from PubMed and Wikipedia in order to investigate the co-morbidities
      of the rare diseases Kaposi sarcoma, toxoplasmosis, and Kawasaki disease. In
      addition to finding well-known characteristics of diseases, ADAMS can identify
      rare or previously unreported associations. In particular, we report a
      statistically significant association between Kawasaki disease and diagnosis of
      autistic disorder.

PMID- 21731657
TI  - Evidence of disseminated intravascular coagulation in a hemorrhagic fever with
      renal syndrome-scoring models and severe illness.
AB  - BACKGROUND: Viral hemorrhagic fevers (VHF) are considered to be a serious threat
      to public health worldwide with up to 100 million cases annually. The general
      hypothesis is that disseminated intravascular coagulation (DIC) is an important
      part of the pathogenesis. The study objectives were to study the variability of
      DIC in consecutive patients with acute hemorrhagic fever with renal syndrome
      (HFRS), and to evaluate if different established DIC-scores can be used as a
      prognostic marker for a more severe illness. METHOD AND FINDINGS: In a
      prospective study 2006-2008, data from 106 patients with confirmed HFRS were
      analyzed and scored for the presence of DIC according to six different templates
      based on criteria from the International Society on Thrombosis and Haemostasis
      (ISTH). The DIC-scoring templates with a fibrinogen/CRP-ratio were most
      predictive, with predictions for moderate/severe illness (p<0.01) and bleeding of
      moderate/major importance (p<0.05). With these templates, 18.9-28.3% of the
      patients were diagnosed with DIC. CONCLUSIONS: DIC was found in about one fourth
      of the patients and correlated with a more severe disease. This supports that DIC
      is an important part of the pathogenesis in HFRS. ISTH-scores including
      fibrinogen/CRP-ratio outperform models without. The high negative predictive
      value could be a valuable tool for the clinician. We also believe that our
      findings could be relevant for other VHFs.

PMID- 21731658
TI  - In silico gene prioritization by integrating multiple data sources.
AB  - Identifying disease genes is crucial to the understanding of disease
      pathogenesis, and to the improvement of disease diagnosis and treatment. In
      recent years, many researchers have proposed approaches to prioritize candidate
      genes by considering the relationship of candidate genes and existing known
      disease genes, reflected in other data sources. In this paper, we propose an
      expandable framework for gene prioritization that can integrate multiple
      heterogeneous data sources by taking advantage of a unified graphic
      representation. Gene-gene relationships and gene-disease relationships are then
      defined based on the overall topology of each network using a diffusion kernel
      measure. These relationship measures are in turn normalized to derive an overall
      measure across all networks, which is utilized to rank all candidate genes. Based
      on the informativeness of available data sources with respect to each specific
      disease, we also propose an adaptive threshold score to select a small subset of
      candidate genes for further validation studies. We performed large scale cross
      validation analysis on 110 disease families using three data sources. Results
      have shown that our approach consistently outperforms other two state of the art
      programs. A case study using Parkinson disease (PD) has identified four candidate
      genes (UBB, SEPT5, GPR37 and TH) that ranked higher than our adaptive threshold,
      all of which are involved in the PD pathway. In particular, a very recent study
      has observed a deletion of TH in a patient with PD, which supports the importance
      of the TH gene in PD pathogenesis. A web tool has been implemented to assist
      scientists in their genetic studies.

PMID- 21731659
TI  - Juvenile hormone regulates extreme mandible growth in male stag beetles.
AB  - The morphological diversity of insects is one of the most striking phenomena in
      biology. Evolutionary modifications to the relative sizes of body parts,
      including the evolution of traits with exaggerated proportions, are responsible
      for a vast range of body forms. Remarkable examples of an insect trait with
      exaggerated proportions are the mandibular weapons of stag beetles. Male stag
      beetles possess extremely enlarged mandibles which they use in combat with rival
      males over females. As with other sexually selected traits, stag beetle mandibles
      vary widely in size among males, and this variable growth results from
      differential larval nutrition. However, the mechanisms responsible for coupling
      nutrition with growth of stag beetle mandibles (or indeed any insect structure)
      remain largely unknown. Here, we demonstrate that during the development of male
      stag beetles (Cyclommatus metallifer), juvenile hormone (JH) titers are
      correlated with the extreme growth of an exaggerated weapon of sexual selection.
      We then investigate the putative role of JH in the development of the
      nutritionally-dependent, phenotypically plastic mandibles, by increasing
      hemolymph titers of JH with application of the JH analog fenoxycarb during larval
      and prepupal developmental periods. Increased JH signaling during the early
      prepupal period increased the proportional size of body parts, and this was
      especially pronounced in male mandibles, enhancing the exaggerated size of this
      trait. The direction of this response is consistent with the measured JH titers
      during this same period. Combined, our results support a role for JH in the
      nutrition-dependent regulation of extreme mandible growth in this species. In
      addition, they illuminate mechanisms underlying the evolution of trait
      proportion, the most salient feature of the evolutionary diversification of the
      insects.

PMID- 21731660
TI  - Independent origins of cultivated coconut (Cocos nucifera L.) in the old world
      tropics.
AB  - As a portable source of food, water, fuel, and construction materials, the
      coconut (Cocos nucifera L.) played a fundamental role in human migrations and the
      development of civilization across the humid tropics. Here we investigated the
      coconut's domestication history and its population genetic structure as it
      relates to human dispersal patterns. A sample of 1,322 coconut accessions,
      representing the geographical and phenotypic diversity of the species, was
      examined using ten microsatellite loci. Bayesian analyses reveal two highly
      genetically differentiated subpopulations that correspond to the Pacific and Indo
      Atlantic oceanic basins. This pattern suggests independent origins of coconut
      cultivation in these two world regions, with persistent population structure on a
      global scale despite long-term human cultivation and dispersal. Pacific coconuts
      show additional genetic substructure corresponding to phenotypic and geographical
      subgroups; moreover, the traits that are most clearly associated with selection
      under human cultivation (dwarf habit, self-pollination, and "niu vai" fruit
      morphology) arose only in the Pacific. Coconuts that show evidence of genetic
      admixture between the Pacific and Indo-Atlantic groups occur primarily in the
      southwestern Indian Ocean. This pattern is consistent with human introductions of
      Pacific coconuts along the ancient Austronesian trade route connecting Madagascar
      to Southeast Asia. Admixture in coastal east Africa may also reflect later
      historic Arab trading along the Indian Ocean coastline. We propose two
      geographical origins of coconut cultivation: island Southeast Asia and southern
      margins of the Indian subcontinent.

PMID- 21731661
TI  - Turning males on: activation of male courtship behavior in Drosophila
      melanogaster.
AB  - The innate sexual behaviors of Drosophila melanogaster males are an attractive
      system for elucidating how complex behavior patterns are generated. The potential
      for male sexual behavior in D. melanogaster is specified by the fruitless (fru)
      and doublesex (dsx) sex regulatory genes. We used the temperature-sensitive
      activator dTRPA1 to probe the roles of fru(M)- and dsx-expressing neurons in male
      courtship behaviors. Almost all steps of courtship, from courtship song to
      ejaculation, can be induced at very high levels through activation of either all
      fru(M) or all dsx neurons in solitary males. Detailed characterizations reveal
      different roles for fru(M) and dsx in male courtship. Surprisingly, the system
      for mate discrimination still works well when all dsx neurons are activated, but
      is impaired when all fru(M) neurons are activated. Most strikingly, we provide
      evidence for a fru(M)-independent courtship pathway that is primarily vision
      dependent.

PMID- 21731662
TI  - A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth
      and enhances NK cells-mediated tumor immunity.
AB  - Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be
      associated with various types of cancers, particularly colorectal carcinoma, and
      developed to be a molecular target for cancer diagnosis and therapy. In present
      study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by
      immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical
      studies found that mAb CC4 specifically and strongly binds to tumor tissues,
      especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is
      specifically accumulated in tumor site and remarkably represses colorectal tumor
      growth. In vitro functional analysis showed that mAb CC4 significantly suppresses
      cell proliferation, migration and aggregation of colorectal cancer cells and also
      raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK
      cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking
      intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor
      CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a
      novel tumor-targeting carrier and cancer therapeutic.

PMID- 21731663
TI  - Plasma chemokine levels are associated with the presence and extent of
      angiographic coronary collaterals in chronic ischemic heart disease.
AB  - BACKGROUND: In patients with chronic ischemic heart disease (IHD), the presence
      and extent of spontaneously visible coronary collaterals are powerful
      determinants of clinical outcome. There is marked heterogeneity in the
      recruitment of coronary collaterals amongst patients with similar degrees of
      coronary artery stenoses, but the biological basis of this heterogeneity is not
      known. Chemokines are potent mediators of vascular remodeling in diverse
      biological settings. Their role in coronary collateralization has not been
      investigated. We sought to determine whether plasma levels of angiogenic and
      angiostatic chemokines are associated with of the presence and extent of coronary
      collaterals in patients with chronic IHD. METHODOLOGY/PRINCIPAL FINDINGS: We
      measured plasma concentrations of angiogenic and angiostatic chemokine ligands in
      156 consecutive subjects undergoing coronary angiography with at least one >=90%
      coronary stenosis and determined the presence and extent of spontaneously visible
      coronary collaterals using the Rentrop scoring system. Eighty-eight subjects
      (56%) had evidence of coronary collaterals. In a multivariable regression model,
      the concentration of the angiogenic ligands CXCL5, CXCL8 and CXCL12,
      hyperlipidemia, and an occluded artery were associated with the presence of
      collaterals; conversely, the concentration of the angiostatic ligand CXCL11,
      interferon-gamma, hypertension and diabetes were associated with the absence of
      collaterals (ROC area 0.91). When analyzed according to extent of
      collateralization, higher Rentrop scores were significantly associated with
      increased concentration of the angiogenic ligand CXCL1 (p<0.0001), and decreased
      concentrations of angiostatic ligands CXCL9 (p<0.0001), CXCL10 (p = 0.002), and
      CXCL11 (p = 0.0002), and interferon-gamma (p = 0.0004). CONCLUSIONS/SIGNIFICANCE:
      Plasma chemokine concentrations are associated with the presence and extent of
      spontaneously visible coronary artery collaterals and may be mechanistically
      involved in their recruitment.

PMID- 21731664
TI  - Complex deleterious interactions associated with malic enzyme may contribute to
      reproductive isolation in the copepod Tigriopus californicus.
AB  - Dobzhansky-Muller incompatibilities can result from the interactions of more than
      a single pair of interacting genes and there are several different models of how
      such complex interactions can be structured. Previous empirical work has
      identified complex conspecific epistasis as a form of complex interaction that
      has contributed to postzygotic reproductive isolation between taxa, but other
      forms of complexity are also possible. Here, I probe the genetic basis of
      reproductive isolation in crosses of the intertidal copepod Tigriopus
      californicus by looking at the impact of markers in genes encoding metabolic
      enzymes in F(2) hybrids. The region of the genome associated with the locus ME2
      is shown to have strong, repeatable impacts on the fitness of hybrids in crosses
      and epistatic interactions with another chromosomal region marked by the GOT2
      locus in one set of crosses. In a cross between one of these populations and a
      third population, these two regions do not appear to interact despite the
      continuation of a large effect of the ME2 region itself in both crosses. The
      combined results suggest that the ME2 chromosomal region is involved in
      incompatibilities with several unique partners. If these deleterious interactions
      all stem from the same factor in this region, that would suggest a different form
      of complexity from complex conspecific epistasis, namely, multiple independent
      deleterious interactions stemming from the same factor. Confirmation of this idea
      will require more fine-scale mapping of the interactions of the ME2 region of the
      genome.

PMID- 21731665
TI  - Weight-related behavior among adolescents: the role of peer effects.
AB  - PURPOSE: To investigate whether social interactions in friendship networks
      influence the following weight-related behaviors of adolescents: exercising
      regularly, playing an active sport, hours of TV/Video viewing, sleeping six or
      fewer hours, eating breakfast on weekdays, frequency of eating at fast food
      restaurants, eating five servings of fruits/vegetables daily, and consuming
      calorie-dense snacks. METHOD: Data from a nationally representative sample of
      adolescents are used to examine the association between peer and individual
      weight-related behaviors. Evidence from multivariate regression analysis
      controlling for an extensive list of individual- and family-level factors as well
      as school-level unobserved heterogeneity is obtained. RESULTS: We find a
      significant positive association between individuals' and friends' behaviors in
      terms of sports, exercise and fast food consumption. The estimated associations
      are robust to controls for individual- and family-level factors, unobserved
      heterogeneity at the school level and our attempts to account for non-random peer
      selection. CONCLUSIONS: The social transmission of weight-related behaviors is a
      viable explanation for the spread of obesity in friendship networks documented in
      recent research. Traditional weight reduction interventions may be fruitfully
      complemented with strategies that focus on harnessing peer support to modify
      behaviors.

PMID- 21731666
TI  - Avian influenza viruses infect primary human bronchial epithelial cells
      unconstrained by sialic acid alpha2,3 residues.
AB  - Avian influenza viruses (AIV) are an important emerging threat to public health.
      It is thought that sialic acid (sia) receptors are barriers in cross-species
      transmission where the binding preferences of AIV and human influenza viruses are
      sias alpha2,3 versus alpha2,6, respectively. In this study, we show that a normal
      fully differentiated, primary human bronchial epithelial cell model is readily
      infected by low pathogenic H5N1, H5N2 and H5N3 AIV, which primarily bind to sia
      alpha2,3 moieties, and replicate in these cells independent of specific sias on
      the cell surface. NHBE cells treated with neuraminidase prior to infection are
      infected by AIV despite removal of sia alpha2,3 moieties. Following AIV
      infection, higher levels of IP-10 and RANTES are secreted compared to human
      influenza virus infection, indicating differential chemokine expression patterns,
      a feature that may contribute to differences in disease pathogenesis between
      avian and human influenza virus infections in humans.

PMID- 21731667
TI  - An observational cohort study of the kynurenine to tryptophan ratio in sepsis:
      association with impaired immune and microvascular function.
AB  - Both endothelial and immune dysfunction contribute to the high mortality rate in
      human sepsis, but the underlying mechanisms are unclear. In response to
      infection, interferon-gamma activates indoleamine 2,3-dioxygenase (IDO) which
      metabolizes the essential amino acid tryptophan to the toxic metabolite
      kynurenine. IDO can be expressed in endothelial cells, hepatocytes and
      mononuclear leukocytes, all of which contribute to sepsis pathophysiology.
      Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in
      plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase
      inhibition. We hypothesized that IDO activity in sepsis would be related to
      plasma interferon-gamma, interleukin-10, T cell lymphopenia and impairment of
      microvascular reactivity, a measure of endothelial nitric oxide bioavailability.
      In an observational cohort study of 80 sepsis patients (50 severe and 30 non
      severe) and 40 hospital controls, we determined the relationship between IDO
      activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric
      oxide-dependent microvascular reactivity and lymphocyte subsets in sepsis. Plasma
      amino acids were measured by high performance liquid chromatography and
      microvascular reactivity by peripheral arterial tonometry. The plasma KT ratio
      was increased in sepsis (median 141 [IQR 64-235]) compared to controls (36 [28
      52]); p<0.0001), and correlated with plasma interferon-gamma and interleukin-10,
      and inversely with total lymphocyte count, CD8+ and CD4+ T-lymphocytes, systolic
      blood pressure and microvascular reactivity. In response to treatment of severe
      sepsis, the median KT ratio decreased from 162 [IQR 100-286] on day 0 to 89 [65
      139] by day 7; p = 0.0006) and this decrease in KT ratio correlated with a
      decrease in the Sequential Organ Failure Assessment score (p<0.0001). IDO
      mediated tryptophan catabolism is associated with dysregulated immune responses
      and impaired microvascular reactivity in sepsis and may link these two
      fundamental processes in sepsis pathophysiology.

PMID- 21731668
TI  - Dietary leucine--an environmental modifier of insulin resistance acting on
      multiple levels of metabolism.
AB  - Environmental factors, such as the macronutrient composition of the diet, can
      have a profound impact on risk of diabetes and metabolic syndrome. In the present
      study we demonstrate how a single, simple dietary factor--leucine--can modify
      insulin resistance by acting on multiple tissues and at multiple levels of
      metabolism. Mice were placed on a normal or high fat diet (HFD). Dietary leucine
      was doubled by addition to the drinking water. mRNA, protein and complete
      metabolomic profiles were assessed in the major insulin sensitive tissues and
      serum, and correlated with changes in glucose homeostasis and insulin signaling.
      After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes
      in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation,
      as well as alterations in metabolomic profile of amino acid metabolites, TCA
      cycle intermediates, glucose and cholesterol metabolites, and fatty acids in
      liver, muscle, fat and serum. Doubling dietary leucine reversed many of the
      metabolite abnormalities and caused a marked improvement in glucose tolerance and
      insulin signaling without altering food intake or weight gain. Increased dietary
      leucine was also associated with a decrease in hepatic steatosis and a decrease
      in inflammation in adipose tissue. These changes occurred despite an increase in
      insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation
      of mTOR, a phenomenon normally associated with insulin resistance. These data
      indicate that modest changes in a single environmental/nutrient factor can modify
      multiple metabolic and signaling pathways and modify HFD induced metabolic
      syndrome by acting at a systemic level on multiple tissues. These data also
      suggest that increasing dietary leucine may provide an adjunct in the management
      of obesity-related insulin resistance.

PMID- 21731669
TI  - Development of bacterial biofilms on artificial corals in comparison to surface
      associated microbes of hard corals.
AB  - Numerous studies have demonstrated the differences in bacterial communities
      associated with corals versus those in their surrounding environment. However,
      these environmental samples often represent vastly different microbial micro
      environments with few studies having looked at the settlement and growth of
      bacteria on surfaces similar to corals. As a result, it is difficult to determine
      which bacteria are associated specifically with coral tissue surfaces. In this
      study, early stages of passive settlement from the water column to artificial
      coral surfaces (formation of a biofilm) were assessed. Changes in bacterial
      diversity (16S rRNA gene), were studied on artificially created resin nubbins
      that were modelled from the skeleton of the reef building coral Acropora
      muricata. These models were dip-coated in sterile agar, mounted in situ on the
      reef and followed over time to monitor bacterial community succession. The
      bacterial community forming the biofilms remained significantly different (R =
      0.864 p<0.05) from that of the water column and from the surface mucus layer
      (SML) of the coral at all times from 30 min to 96 h. The water column was
      dominated by members of the alpha-proteobacteria, the developed community on the
      biofilms dominated by gamma-proteobacteria, whereas that within the SML was
      composed of a more diverse array of groups. Bacterial communities present within
      the SML do not appear to arise from passive settlement from the water column, but
      instead appear to have become established through a selection process. This
      selection process was shown to be dependent on some aspects of the physico
      chemical structure of the settlement surface, since agar-coated slides showed
      distinct communities to coral-shaped surfaces. However, no significant
      differences were found between different surface coatings, including plain agar
      and agar enhanced with coral mucus exudates. Therefore future work should
      consider physico-chemical surface properties as factors governing change in
      microbial diversity.

PMID- 21731670
TI  - Long-term effects of the cleaner fish Labroides dimidiatus on coral reef fish
      communities.
AB  - Cleaning behaviour is deemed a mutualism, however the benefit of cleaning
      interactions to client individuals is unknown. Furthermore, mechanisms that may
      shift fish community structure in the presence of cleaning organisms are unclear.
      Here we show that on patch reefs (61-285 m2) which had all cleaner wrasse
      Labroides dimidiatus (Labridae) experimentally removed (1-5 adults reef-1) and
      which were then maintained cleaner-fish free over 8.5 years, individuals of two
      site-attached (resident) client damselfishes (Pomacentridae) were smaller
      compared to those on control reefs. Furthermore, resident fishes were 37% less
      abundant and 23% less species rich per reef, compared to control reefs. Such
      changes in site-attached fish may reflect lower fish growth rates and/or
      survivorship. Additionally, juveniles of visitors (fish likely to move between
      reefs) were 65% less abundant on removal reefs suggesting cleaners may also
      affect recruitment. This may, in part, explain the 23% lower abundance and 33%
      lower species richness of visitor fishes, and 66% lower abundance of visitor
      herbivores (Acanthuridae) on removal reefs that we also observed. This is the
      first study to demonstrate a benefit of cleaning behaviour to client individuals,
      in the form of increased size, and to elucidate potential mechanisms leading to
      community-wide effects on the fish population. Many of the fish groups affected
      may also indirectly affect other reef organisms, thus further impacting the reef
      community. The large-scale effect of the presence of the relatively small and
      uncommon fish, Labroides dimidiadus, on other fishes is unparalleled on coral
      reefs.

PMID- 21731671
TI  - Securinine, a myeloid differentiation agent with therapeutic potential for AML.
AB  - As the defining feature of Acute Myeloid Leukemia (AML) is a maturation arrest, a
      highly desirable therapeutic strategy is to induce leukemic cell maturation. This
      therapeutic strategy has the potential of avoiding the significant side effects
      that occur with the traditional AML therapeutics. We identified a natural
      compound securinine, as a leukemia differentiation-inducing agent. Securinine is
      a plant-derived alkaloid that has previously been used clinically as a
      therapeutic for primarily neurological related diseases. Securinine induces
      monocytic differentiation of a wide range of myeloid leukemia cell lines as well
      as primary leukemic patient samples. Securinine's clinical potential for AML can
      be seen from its ability to induce significant growth arrest in cell lines and
      patient samples as well as its activity in significantly impairing the growth of
      AML tumors in nude mice. In addition, securinine can synergize with currently
      employed agents such as ATRA and decitabine to induce differentiation. This study
      has revealed securinine induces differentiation through the activation of DNA
      damage signaling. Securinine is a promising new monocytic differentiation
      inducing agent for AML that has seen previous clinical use for non-related
      disorders.

PMID- 21731672
TI  - Testing the applicability of Nernst-Planck theory in ion channels: comparisons
      with Brownian dynamics simulations.
AB  - The macroscopic Nernst-Planck (NP) theory has often been used for predicting ion
      channel currents in recent years, but the validity of this theory at the
      microscopic scale has not been tested. In this study we systematically tested the
      ability of the NP theory to accurately predict channel currents by combining and
      comparing the results with those of Brownian dynamics (BD) simulations. To
      thoroughly test the theory in a range of situations, calculations were made in a
      series of simplified cylindrical channels with radii ranging from 3 to 15 A, in a
      more complex 'catenary' channel, and in a realistic model of the mechanosensitive
      channel MscS. The extensive tests indicate that the NP equation is applicable in
      narrow ion channels provided that accurate concentrations and potentials can be
      input as the currents obtained from the combination of BD and NP match well with
      those obtained directly from BD simulations, although some discrepancies are seen
      when the ion concentrations are not radially uniform. This finding opens a door
      to utilising the results of microscopic simulations in continuum theory,
      something that is likely to be useful in the investigation of a range of
      biophysical and nano-scale applications and should stimulate further studies in
      this direction.

PMID- 21731673
TI  - Deterministic and stochastic allele specific gene expression in single mouse
      blastomeres.
AB  - Stochastic and deterministic allele specific gene expression (ASE) might
      influence single cell phenotype, but the extent and nature of the phenomenon at
      the onset of early mouse development is unknown. Here we performed single cell
      RNA-Seq analysis of single blastomeres of mouse embryos, which revealed
      significant changes in the transcriptome. Importantly, over half of the
      transcripts with detectable genetic polymorphisms exhibit ASE, most notably,
      individual blastomeres from the same two-cell embryo show similar pattern of ASE.
      However, about 6% of them exhibit stochastic expression, indicated by altered
      expression ratio between the two alleles. Thus, we demonstrate that ASE is both
      deterministic and stochastic in early blastomeres. Furthermore, we also found
      that 1,718 genes express two isoforms with different lengths of 3'UTRs, with the
      shorter one on average 5-6 times more abundant in early blastomeres compared to
      the transcripts in epiblast cells, suggesting that microRNA mediated regulation
      of gene expression acquires increasing importance as development progresses.

PMID- 21731674
TI  - An information theoretic, microfluidic-based single cell analysis permits
      identification of subpopulations among putatively homogeneous stem cells.
AB  - An incomplete understanding of the nature of heterogeneity within stem cell
      populations remains a major impediment to the development of clinically effective
      cell-based therapies. Transcriptional events within a single cell are inherently
      stochastic and can produce tremendous variability, even among genetically
      identical cells. It remains unclear how mammalian cellular systems overcome this
      intrinsic noisiness of gene expression to produce consequential variations in
      function, and what impact this has on the biologic and clinical relevance of
      highly 'purified' cell subgroups. To address these questions, we have developed a
      novel method combining microfluidic-based single cell analysis and information
      theory to characterize and predict transcriptional programs across hundreds of
      individual cells. Using this technique, we demonstrate that multiple
      subpopulations exist within a well-studied and putatively homogeneous stem cell
      population, murine long-term hematopoietic stem cells (LT-HSCs). These subgroups
      are defined by nonrandom patterns that are distinguishable from noise and are
      consistent with known functional properties of these cells. We anticipate that
      this analytic framework can also be applied to other cell types to elucidate the
      relationship between transcriptional and phenotypic variation.

PMID- 21731675
TI  - Factors associated with negative direct sputum examination in Asian and African
      HIV-infected patients with tuberculosis (ANRS 1260).
AB  - OBJECTIVE: To identify factors associated with negative direct sputum examination
      among African and Cambodian patients co-infected by Mycobacterium tuberculosis
      and HIV. DESIGN: Prospective multicenter study (ANRS1260) conducted in Cambodia,
      Senegal and Central African Republic. METHODS: Univariate and multivariate
      analyses (logistic regression) were used to identify clinical and radiological
      features associated with negative direct sputum examination in HIV-infected
      patients with positive M. tuberculosis culture on Lowenstein-Jensen medium.
      RESULTS: Between September 2002 and December 2005, 175 co-infected patients were
      hospitalized with at least one respiratory symptom and pulmonary radiographic
      anomaly. Acid-fast bacillus (AFB) examination was positive in sputum samples from
      110 subjects (63%) and negative in 65 patients (37%). Most patients were at an
      advanced stage of HIV disease (92% at stage III or IV of the WHO classification)
      with a median CD4 cell count of 36/mm3. In this context, we found that sputum AFB
      negativity was more frequent in co-infected subjects with associated respiratory
      tract infections (OR = 2.8 [95%CI:1.1-7.0]), dyspnea (OR = 2.5 [95%CI:1.1-5.6]),
      and localized interstitial opacities (OR = 3.1 [95%CI:1.3-7.6]), but was less
      frequent with CD4 <= 50/mm3 (OR = 0.4 [95%CI:0.2-0.90), adenopathies (OR = 0.4
      [95%CI:0.2-0.93]) and cavitation (OR = 0.1 [95%CI:0.03-0.6]). CONCLUSIONS: One
      novel finding of this study is the association between concomitant respiratory
      tract infection and negative sputum AFB, particularly in Cambodia. This finding
      suggests that repeating AFB testing in AFB-negative patients should be conducted
      when broad spectrum antibiotic treatment does not lead to complete recovery from
      respiratory symptoms. In HIV-infected patients with a CD4 cell count below 50/mm3
      without an identified cause of pneumonia, systematic AFB direct sputum
      examination is justified because of atypical clinical features (without
      cavitation) and high pulmonary mycobacterial burden.

PMID- 21731676
TI  - Detection of intra-tumor self antigen recognition during melanoma tumor
      progression in mice using advanced multimode confocal/two photon microscope.
AB  - Determining how tumor immunity is regulated requires understanding the extent to
      which the anti-tumor immune response "functions" in vivo without therapeutic
      intervention. To better understand this question, we developed advanced
      multimodal reflectance confocal/two photon fluorescence intra-vital imaging
      techniques to use in combination with traditional ex vivo analysis of tumor
      specific T cells. By transferring small numbers of melanoma-specific CD8+ T cells
      (Pmel-1), in an attempt to mimic physiologic conditions, we found that B16 tumor
      growth alone was sufficient to induce naive Pmel-1 T cell proliferation and
      acquisition of effector phenotype. Tumor -primed Pmel-1 T cells, are capable of
      killing target cells in the periphery and secrete IFNgamma, but are unable to
      mediate tumor regression. Within the tumor, Pmel-1 T cells have highly confined
      mobility, displaying long term interactions with tumor cells. In contrast,
      adoptively transferred non tumor-specific OT-I T cells show neither confined
      mobility, nor long term interaction with B16 tumor cells, suggesting that intra
      tumor recognition of cognate self antigen by Pmel-1 T cells occurs during tumor
      growth. Together, these data indicate that lack of anti-tumor efficacy is not
      solely due to ignorance of self antigen in the tumor microenvironment but rather
      to active immunosuppressive influences preventing a protective immune response.

PMID- 21731677
TI  - Daidzein prevents the increase in CD4+CD28null T cells and B lymphopoesis in
      ovariectomized mice: a key mechanism for anti-osteoclastogenic effect.
AB  - Estrogen deficiency leads to an upregulation of TNF-alpha producing T cells and B
      lymphopoesis which augments osteoclastogenesis. Estrogen deficiency also
      increases the population of premature senescent CD4+ CD28null T cells which
      secrete a higher amount of TNF-alpha thus leading to enhanced osteoclastogenesis.
      Isoflavonoids like daidzein and genistein are found mostly in soybeans, legumes,
      and peas. These share structural similarity with 17beta-stradiol (E2) and have
      osteoprotective role. This study explores the effect of daidzein (Daid) on the
      proliferation of TNF-alpha producing T cells, premature senescent T cells and B
      cell lymphopoesis under estrogen deficient conditions. For this study adult
      Balb/c mice were treated with Daid at 10 mg/kg body weight dose by oral gavage
      daily post ovariectomy (Ovx). After six weeks animals were autopsied and bone
      marrow and spleen cells were collected for FACS analysis. Blood serum was
      collected for ELISA. It was observed that Ovx mice treated with Daid for six
      weeks show reduction in Ovx induced expansion of CD4+ T cells in bone marrow and
      spleen when analysed by flow cytometry. Estrogen deficiency led to increased
      prevalence of TNF-alpha secreting CD4+CD28null T cells, however, treatment with
      Daid increased the percentage of CD4+CD28+ T cells. Co-culture of CD4+CD28null T
      cells and bone marrow resulted in enhanced osteoclastogenesis as evident by
      increased tartarate resistant acid phosphatase (TRAP) expression, an osteoclast
      marker. However, treatment with Daid resulted in reduced osteoclastogenesis in
      CD4+CD28null T cells and bone marrow cell co-culture. Daid also regulated B
      lymphopoesis and decreased mRNA levels of RANKL in B220+ cells. Taken together,
      we propose that one of the mechanisms by which Daid prevents bone loss is by
      reversing the detrimental immune changes as a result of estrogen deficiency.

PMID- 21731678
TI  - The first insight into the tissue specific taxus transcriptome via Illumina
      second generation sequencing.
AB  - BACKGROUND: Illumina second generation sequencing is now an efficient route for
      generating enormous sequence collections that represent expressed genes and
      quantitate expression level. Taxus is a world-wide endangered gymnosperm genus
      and forms an important anti-cancer medicinal resource, but the large and complex
      genomes of Taxus have hindered the development of genomic resources. The research
      of its tissue-specific transcriptome is absent. There is also no study concerning
      the association between the plant transcriptome and metabolome with respect to
      the plant tissue type. METHODOLOGY/PRINCIPAL FINDINGS: We performed the de novo
      assembly of Taxus mairei transcriptome using Illumina paired-end sequencing
      technology. In a single run, we produced 13,737,528 sequencing reads
      corresponding to 2.03 Gb total nucleotides. These reads were assembled into
      36,493 unique sequences. Based on similarity search with known proteins, 23,515
      Unigenes were identified to have the Blast hit with a cut-off E-value above 10-5.
      Furthermore, we investigated the transcriptome difference of three Taxus tissues
      using a tag-based digital gene expression system. We obtained a sequencing depth
      of over 3.15 million tags per sample and identified a large number of genes
      associated with tissue specific functions and taxane biosynthetic pathway. The
      expression of the taxane biosynthetic genes is significantly higher in the root
      than in the leaf and the stem, while high activity of taxane-producing pathway in
      the root was also revealed via metabolomic analyses. Moreover, many antisense
      transcripts and novel transcripts were found; clusters with similar differential
      expression patterns, enriched GO terms and enriched metabolic pathways with
      regard to the differentially expressed genes were revealed for the first time.
      CONCLUSIONS/SIGNIFICANCE: Our data provides the most comprehensive sequence
      resource available for Taxus study and will help define mechanisms of tissue
      specific functions and secondary metabolism in non-model plant organisms.

PMID- 21731679
TI  - The intensity of IUGR-induced transcriptome deregulations is inversely correlated
      with the onset of organ function in a rat model.
AB  - A low-protein diet applied during pregnancy in the rat results in intrauterine
      growth restricted (IUGR) fetuses. In humans, IUGR is associated with increased
      perinatal morbidity, higher incidence of neuro-developmental defects and
      increased risk of adult metabolic anomalies, such as diabetes and cardiovascular
      disease. Development and function of many organs are affected by environmental
      conditions such as those inducing fetal and early postnatal growth restriction.
      This phenomenon, termed "fetal programming" has been studied unconnectedly in
      some organs, but very few studies (if any) have investigated at the same time
      several organs, on a more comparative basis. However, it is quite probable that
      IUGR affects differentially most organ systems, with possible persistent changes
      in gene expression. In this study we address transcriptional alterations induced
      by IUGR in a multi-organ perspective, by systematic analysis of 20-days rat
      fetuses. We show that (1) expressional alterations are apparently stronger in
      organs functioning late in foetal or postnatal life than in organs that are
      functioning early (2) hierarchical classification of the deregulations put
      together kidney and placenta in one cluster, liver, lungs and heart in another;
      (3) the epigenetic machinery is set up especially in the placenta, while its
      alterations are rather mild in other organs; (4) the genes appear deregulated in
      chromosome clusters; (5) the altered expression cascades varies from organ to
      organ, with noticeably a very significant modification of the complement and
      coagulation cascades in the kidney; (6) we found a significant increase in TF
      binding site for HNF4 proteins specifically for liver genes that are down
      regulated in IUGR, suggesting that this decrease is achieved through the action
      of HNF transcription factors, that are themselves transcriptionnally induced in
      the liver by IUGR (x 1.84 fold). Altogether, our study suggests that a
      combination of tissue-specific mechanisms contributes to bring about tissue
      driven modifications of gene cascades. The question of these cascades being
      activated to adapt the organ to harsh environmental condition, or as an endpoint
      consequence is still raised.

PMID- 21731680
TI  - The TIP30 protein complex, arachidonic acid and coenzyme A are required for
      vesicle membrane fusion.
AB  - Efficient membrane fusion has been successfully mimicked in vitro using
      artificial membranes and a number of cellular proteins that are currently known
      to participate in membrane fusion. However, these proteins are not sufficient to
      promote efficient fusion between biological membranes, indicating that critical
      fusogenic factors remain unidentified. We have recently identified a TIP30
      protein complex containing TIP30, acyl-CoA synthetase long-chain family member 4
      (ACSL4) and Endophilin B1 (Endo B1) that promotes the fusion of endocytic
      vesicles with Rab5a vesicles, which transport endosomal acidification enzymes
      vacuolar (H+)-ATPases (V-ATPases) to the early endosomes in vivo. Here, we
      demonstrate that the TIP30 protein complex facilitates the fusion of endocytic
      vesicles with Rab5a vesicles in vitro. Fusion of the two vesicles also depends on
      arachidonic acid, coenzyme A and the synthesis of arachidonyl-CoA by ACSL4.
      Moreover, the TIP30 complex is able to transfer arachidonyl groups onto
      phosphatidic acid (PA), producing a new lipid species that is capable of inducing
      close contact between membranes. Together, our data suggest that the TIP30
      complex facilitates biological membrane fusion through modification of PA on
      membranes.

PMID- 21731681
TI  - Deep sequencing of ESTs from nacreous and prismatic layer producing tissues and a
      screen for novel shell formation-related genes in the pearl oyster.
AB  - BACKGROUND: Despite its economic importance, we have a limited understanding of
      the molecular mechanisms underlying shell formation in pearl oysters, wherein the
      calcium carbonate crystals, nacre and prism, are formed in a highly controlled
      manner. We constructed comprehensive expressed gene profiles in the shell-forming
      tissues of the pearl oyster Pinctada fucata and identified novel shell formation
      related genes candidates. PRINCIPAL FINDINGS: We employed the GS FLX 454 system
      and constructed transcriptome data sets from pallial mantle and pearl sac, which
      form the nacreous layer, and from the mantle edge, which forms the prismatic
      layer in P. fucata. We sequenced 260477 reads and obtained 29682 unique
      sequences. We also screened novel nacreous and prismatic gene candidates by a
      combined analysis of sequence and expression data sets, and identified various
      genes encoding lectin, protease, protease inhibitors, lysine-rich matrix protein,
      and secreting calcium-binding proteins. We also examined the expression of known
      nacreous and prismatic genes in our EST library and identified novel isoforms
      with tissue-specific expressions. CONCLUSIONS: We constructed EST data sets from
      the nacre- and prism-producing tissues in P. fucata and found 29682 unique
      sequences containing novel gene candidates for nacreous and prismatic layer
      formation. This is the first report of deep sequencing of ESTs in the shell
      forming tissues of P. fucata and our data provide a powerful tool for a
      comprehensive understanding of the molecular mechanisms of molluscan
      biomineralization.

PMID- 21731682
TI  - Mass-specific metabolic rate and sperm competition determine sperm size in
      marsupial mammals.
AB  - Two complementary hypotheses have been proposed to explain variation in sperm
      size. The first proposes that post-copulatory sexual selection favors an increase
      in sperm size because it enhances sperm swimming speed, which is an important
      determinant of fertilization success in competitive contexts. The second
      hypothesis proposes that mass-specific metabolic rate acts as a constraint,
      because large animals with low mass-specific metabolic rates will not be able to
      process resources at the rates needed to produce large sperm. This constraint is
      expected to be particularly pronounced among mammals, given that this group
      contains some of the largest species on Earth. We tested these hypotheses among
      marsupials, a group in which mass-specific metabolic rates are roughly 30% lower
      than those of eutherian mammals of similar size, leading to the expectation that
      metabolic rate should be a major constraint. Our findings support both hypotheses
      because levels of sperm competition are associated with increases in sperm size,
      but low mass-specific metabolic rate constrains sperm size among large species.
      We also found that the relationship between sperm size and mass-specific
      metabolic rate is steeper among marsupials and shallower among eutherian mammals.
      This finding has two implications: marsupials respond to changes in mass-specific
      metabolic rate by modifying sperm length to a greater extent, suggesting that
      they are more constrained by metabolic rate. In addition, for any given mass
      specific metabolic rate, marsupials produce longer sperm. We suggest that this is
      the consequence of marsupials diverting resources away from sperm numbers and
      into sperm size, due to their efficient sperm transport along the female tract
      and the existence of mechanisms to protect sperm.

PMID- 21731683
TI  - Enrichment of sialylated IgG by lectin fractionation does not enhance the
      efficacy of immunoglobulin G in a murine model of immune thrombocytopenia.
AB  - Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical
      symptoms. For its use in immune modulating therapies such as treatment of immune
      thrombocytopenic purpura high doses of IVIg are required. It has been suggested
      that only a fraction of IVIg causes this anti immune modulating effect. Recent
      studies indicated that this fraction is the Fc-sialylated IgG fraction. The aim
      of our study was to determine the efficacy of IVIg enriched for sialylated IgG
      (IVIg-SA+) in a murine model of passive immune thrombocytopenia (PIT). We
      enriched IVIg for sialylated IgG by Sambucus nigra agglutinin (SNA) lectin
      fractionation and determined the degree of sialylation. Analysis of IVIg-SA+
      using a lectin-based ELISA revealed that we enriched predominantly for Fab
      sialylated IgG, whereas we did not find an increase in Fc-sialylated IgG. Mass
      spectrometric analysis confirmed that Fc sialylation did not change after SNA
      lectin fractionation. The efficacy of sialylated IgG was measured by
      administering IVIg or IVIg-SA+ 24 hours prior to an injection of a rat anti-mouse
      platelet mAb. We found an 85% decrease in platelet count after injection of an
      anti-platelet mAb, which was reduced to a 70% decrease by injecting IVIg
      (p<0.01). In contrast, IVIg-SA+ had no effect on the platelet count. Serum levels
      of IVIg and IVIg-SA+ were similar, ruling out enhanced IgG clearance as a
      possible explanation. Our results indicate that SNA lectin fractionation is not a
      suitable method to enrich IVIg for Fc-sialylated IgG. The use of IVIg enriched
      for Fab-sialylated IgG abolishes the efficacy of IVIg in the murine PIT model.

PMID- 21731684
TI  - Transformation of human mesenchymal cells and skin fibroblasts into hematopoietic
      cells.
AB  - Patients with prolonged myelosuppression require frequent platelet and occasional
      granulocyte transfusions. Multi-donor transfusions induce alloimmunization,
      thereby increasing morbidity and mortality. Therefore, an autologous or HLA
      matched allogeneic source of platelets and granulocytes is needed. To determine
      whether nonhematopoietic cells can be reprogrammed into hematopoietic cells,
      human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with
      the demethylating agent 5-azacytidine (Aza) and the growth factors (GF)
      granulocyte-macrophage colony-stimulating factor and stem cell factor. This
      treatment transformed MSCs to round, non-adherent cells expressing T-, B-,
      myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as
      hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and
      mRNA array analysis suggested that Aza and GF treatment demethylated and
      activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with
      HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further
      studies are needed to determine whether transformed MSCs or skin fibroblasts are
      suitable for therapy.

PMID- 21731685
TI  - Phylogenetic beta diversity metrics, trait evolution and inferring the functional
      beta diversity of communities.
AB  - The beta diversity of communities along gradients has fascinated ecologists for
      decades. Traditionally such studies have focused on the species composition of
      communities, but researchers are becoming increasingly interested in analyzing
      the phylogenetic composition in the hope of achieving mechanistic insights into
      community structure. To date many metrics of phylogenetic beta diversity have
      been published, but few empirical studies have been published. Further inferences
      made from such phylogenetic studies critically rely on the pattern of trait
      evolution. The present work provides a study of the phylogenetic dissimilarity of
      96 tree communities in India. The work compares and contrasts eight metrics of
      phylogenetic dissimilarity, considers the role of phylogenetic signal in trait
      data and shows that environmental distance rather than spatial distance is the
      best correlate of phylogenetic dissimilarity in the study system.

PMID- 21731686
TI  - Concurrent detection of circulating minor histocompatibility antigen-specific
      CD8+ T cells in SCT recipients by combinatorial encoding MHC multimers.
AB  - Allogeneic stem cell transplantation (SCT) is a potentially curative treatment
      for patients with hematologic malignancies. Its therapeutic effect is largely
      dependent on recognition of minor histocompatibility antigens (MiHA) by donor
      derived CD8+ T cells. Therefore, monitoring of multiple MiHA-specific CD8+ T cell
      responses may prove to be valuable for evaluating the efficacy of allogeneic SCT.
      In this study, we investigated the use of the combinatorial encoding MHC multimer
      technique to simultaneously detect MiHA-specific CD8+ T cells in peripheral blood
      of SCT recipients. Feasibility of this approach was demonstrated by applying dual
      color encoding MHC multimers for a set of 10 known MiHA. Interestingly, single
      staining using a fluorochrome- and Qdot-based five-color combination showed
      comparable results to dual-color staining for most MiHA-specific CD8+ T cell
      responses. In addition, we determined the potential value of combinatorial
      encoding MHC multimers in MiHA identification. Therefore, a set of 75 candidate
      MiHA peptides was predicted from polymorphic genes with a hematopoietic
      expression profile and further selected for high and intermediate binding
      affinity for HLA-A2. Screening of a large cohort of SCT recipients resulted in
      the detection of dual-color encoded CD8+ T cells following MHC multimer-based T
      cell enrichment and short ex vivo expansion. Interestingly, candidate MiHA
      specific CD8+ T cell responses for LAG3 and TLR10 derived polymorphic peptides
      could be confirmed by genotyping of the respective SNPs. These findings
      demonstrate the potency of the combinatorial MHC multimer approach in the
      monitoring of CD8+ T cell responses to known and potential MiHA in limited
      amounts of peripheral blood from allogeneic SCT recipients.

PMID- 21731687
TI  - Expression of enzymatically inactive wasp venom phospholipase A1 in Pichia
      pastoris.
AB  - Wasp venom allergy is the most common insect venom allergy in Europe. It is
      manifested by large local reaction or anaphylactic shock occurring after a wasp
      sting. The allergy can be treated by specific immunotherapy with whole venom
      extracts. Wasp venom is difficult and costly to obtain and is a subject to
      composition variation, therefore it can be advantageous to substitute it with a
      cocktail of recombinant allergens. One of the major venom allergens is
      phospholipase A1, which so far has been expressed in Escherichia coli and in
      insect cells. Our aim was to produce the protein in secreted form in yeast Pichia
      pastoris, which can give high yields of correctly folded protein on defined
      minimal medium and secretes relatively few native proteins simplifying
      purification.Residual amounts of enzymatically active phospholipase A1 could be
      expressed, but the venom protein had a deleterious effect on growth of the yeast
      cells. To overcome the problem we introduced three different point mutations at
      the critical points of the active site, where serine137, aspartate165 or
      histidine229 were replaced by alanine (S137A, D165A and H229A). All the three
      mutated forms could be expressed in P. pastoris. The H229A mutant did not have
      any detectable phospholipase A1 activity and was secreted at the level of several
      mg/L in shake flask culture. The protein was purified by nickel-affinity
      chromatography and its identity was confirmed by MALDI-TOF mass spectrometry. The
      protein could bind IgE antibodies from wasp venom allergic patients and could
      inhibit the binding of wasp venom to IgE antibodies specific for phospholipase A1
      as shown by Enzyme Allergo-Sorbent Test (EAST). Moreover, the recombinant protein
      was allergenic in a biological assay as demonstrated by its capability to induce
      histamine release of wasp venom-sensitive basophils.The recombinant phospholipase
      A1 presents a good candidate for wasp venom immunotherapy.

PMID- 21731688
TI  - The Streptococcus pneumoniae pilus-1 displays a biphasic expression pattern.
AB  - The Streptococcus pneumoniae pilus-1 is encoded by pilus islet 1 (PI-1), which
      has three clonal variants (clade I, II and III) and is present in about 30% of
      clinical pneumococcal isolates. In vitro and in vivo assays have demonstrated
      that pilus-1 is involved in attachment to epithelial cells and virulence, as well
      as protection in mouse models of infection. Several reports suggest that pilus-1
      expression is tightly regulated and involves the interplay of numerous genetic
      regulators, including the PI-1 positive regulator RlrA. In this report we provide
      evidence that pilus expression, when analyzed at the single-cell level in PI-1
      positive strains, is biphasic. In fact, the strains present two phenotypically
      different sub-populations of bacteria, one that expresses the pilus, while the
      other does not. The proportions of these two phenotypes are variable among the
      strains tested and are not influenced by genotype, serotype, growth conditions,
      colony morphology or by the presence of antibodies directed toward the pilus
      components. Two sub-populations, enriched in pilus expressing or not expressing
      bacteria were obtained by means of colony selection and immuno-detection methods
      for five strains. PI-1 sequencing in the two sub-populations revealed the absence
      of mutations, thus indicating that the biphasic expression observed is not due to
      a genetic modification within PI-1. Microarray expression profile and western
      blot analyses on whole bacterial lysates performed comparing the two enriched sub
      populations, revealed that pilus expression is regulated at the transcriptional
      level (on/off regulation), and that there are no other genes, in addition to
      those encoded by PI-1, concurrently regulated across the strains tested. Finally,
      we provide evidence that the over-expression of the RrlA positive regulator is
      sufficient to induce pilus expression in pilus-1 negative bacteria. Overall, the
      data presented here suggest that the observed biphasic pilus expression phenotype
      could be an example of bistability in pneumococcus.

PMID- 21731689
TI  - Unraveling a 146 years old taxonomic puzzle: validation of Malabar snakehead,
      species-status and its relevance for channid systematics and evolution.
AB  - BACKGROUND: The Malabar snakehead Channa diplogramma is one of the most enigmatic
      and least understood species within the family Channidae, which comprise one of
      the most important groups of freshwater food fish in tropical Asia. Since its
      description from peninsular India in 1865, it has remained a taxonomic puzzle
      with many researchers questioning its validity, based on its striking similarity
      with the South East Asian C. micropeltes. In this study, we assessed the identity
      of the Malabar snakehead, C. diplogramma, using morphological and molecular
      genetic analyses, and also evaluated its phylogenetic relationships and
      evolutionary biogeography. METHODOLOGY/PRINCIPAL FINDINGS: The morphometric and
      meristic analysis provided conclusive evidence to separate C. diplogramma and C.
      micropeltes as two distinct species. Number of caudal fin rays, lateral line
      scales, scales below lateral line; total vertebrae, pre-anal length and body
      depth were the most prominent characters that can be used to differentiate both
      the species. Channa diplogramma also shows several ontogenic color phases during
      its life history, which is shared with C. micropeltes. Finally, the genetic
      distance between both species for the partial mitochondrial 16S rRNA and COI
      sequences is also well above the intra-specific genetic distances of any other
      channid species compared in this study. CONCLUSIONS/SIGNIFICANCE: The current
      distribution of C. diplogramma and C. micropeltes is best explained by
      vicariance. The significant variation in the key taxonomic characters and the
      results of the molecular marker analysis points towards an allopatric speciation
      event or vicariant divergence from a common ancestor, which molecular data
      suggests to have occurred as early as 21.76 million years ago. The resurrection
      of C. diplogramma from the synonymy of C. micropeltes has hence been confirmed
      146 years after its initial description and 134 years after it was synonymised,
      establishing it is an endemic species of peninsular India and prioritizing its
      conservation value.

PMID- 21731690
TI  - Endotoxemia is associated with altered innate and adaptive immune responses in
      untreated HIV-1 infected individuals.
AB  - BACKGROUND: Microbial translocation may contribute to the immunopathogenesis in
      HIV infection. We investigated if microbial translocation and inflammation were
      associated with innate and adaptive immune responses in adults with HIV.
      METHODOLOGY/PRINCIPAL FINDINGS: This was an observational cohort study. Sera from
      HIV-infected and HIV-uninfected individuals were analyzed for microbial
      translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody,
      and anti-alpha-galactosyl antibodies) and inflammatory markers (high sensitivity
      C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor
      receptor II, and IL-10) with enzyme-linked immunosorbent assays. Peripheral blood
      mononuclear cells (PBMC) from HIV-infected persons and healthy controls (primed
      with single-stranded HIV-1-derived RNA) were stimulated with LPS, and cytokine
      production was measured. Finally, HIV-infected patients were immunized with
      Prevnar 7vPnC+/-CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial
      translocation and inflammation on immunization were analyzed in a predictive
      regression model. We included 96 HIV-infected individuals, 76 on highly active
      antiretroviral therapy (HAART), 20 HAART-naive, and 50 healthy controls.
      Microbial translocation and inflammatory markers were higher among HIV-infected
      persons than controls. Cytokine levels following LPS stimulation were increased
      in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons.
      Further, RNA-priming of PBMCs from controls acted synergistically with LPS to
      augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine
      responses among HAART-naive, but not among HAART-treated HIV-infected
      individuals. CONCLUSIONS/SIGNIFICANCE: LPS acts synergistically with HIV RNA to
      stimulate innate immune responses in vitro and increasing serum LPS levels seem
      to predict poor antibody responses after vaccination among HAART-naive HIV
      infected persons. Thus, our results suggest that microbial translocation may be
      associated with innate and adaptive immune dysfunction in untreated HIV
      infection.

PMID- 21731691
TI  - Immunoglobulin G locus events in soft tissue sarcoma cell lines.
AB  - Recently immunoglobulins (Igs) have been found to be expressed by cells other
      than B lymphocytes, including various human carcinoma cells. Sarcomas are derived
      from mesenchyme, and the knowledge about the occurrence of Ig production in
      sarcoma cells is very limited. Here we investigated the phenomenon of
      immunoglobulin G (IgG) expression and its molecular basis in 3 sarcoma cell
      lines. The mRNA transcripts of IgG heavy chain and kappa light chain were
      detected by RT-PCR. In addition, the expression of IgG proteins was confirmed by
      Western blot and immunofluorescence. Immuno-electron microscopy localized IgG to
      the cell membrane and rough endoplasmic reticulum. The essential enzymes required
      for gene rearrangement and class switch recombination, and IgG germ-line
      transcripts were also identified in these sarcoma cells. Chromatin
      immunoprecipitation results demonstrated histone H3 acetylation of both the
      recombination activating gene and Ig heavy chain regulatory elements.
      Collectively, these results confirmed IgG expression in sarcoma cells, the
      mechanism of which is very similar to that regulating IgG expression in B
      lymphocytes.

PMID- 21731692
TI  - Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV).
AB  - The lack of a suitable small animal model for the analysis of hepatitis C virus
      (HCV) infection has hampered elucidation of the HCV life cycle and the
      development of both protective and therapeutic strategies against HCV infection.
      Human and mouse harbor a comparable system for antiviral type I interferon (IFN)
      induction and amplification, which regulates viral infection and replication.
      Using hepatocytes from knockout (ko) mice, we determined the critical step of the
      IFN-inducing/amplification pathways regulating HCV replication in mouse. The
      results infer that interferon-beta promoter stimulator (IPS-1) or interferon A
      receptor (IFNAR) were a crucial barrier to HCV replication in mouse hepatocytes.
      Although both IFNARko and IPS-1ko hepatocytes showed a reduced induction of type
      I interferons in response to viral infection, only IPS-1-/- cells circumvented
      cell death from HCV cytopathic effect and significantly improved J6JFH1
      replication, suggesting IPS-1 to be a key player regulating HCV replication in
      mouse hepatocytes. We then established mouse hepatocyte lines lacking IPS-1 or
      IFNAR through immortalization with SV40T antigen. Expression of human (h)CD81 on
      these hepatocyte lines rendered both lines HCVcc-permissive. We also found that
      the chimeric J6JFH1 construct, having the structure region from J6 isolate
      enhanced HCV replication in mouse hepatocytes rather than the full length
      original JFH1 construct, a new finding that suggests the possible role of the HCV
      structural region in HCV replication. This is the first report on the entry and
      replication of HCV infectious particles in mouse hepatocytes. These mouse
      hepatocyte lines will facilitate establishing a mouse HCV infection model with
      multifarious applications.

PMID- 21731693
TI  - The energetic cost of walking: a comparison of predictive methods.
AB  - BACKGROUND: The energy that animals devote to locomotion has been of intense
      interest to biologists for decades and two basic methodologies have emerged to
      predict locomotor energy expenditure: those based on metabolic and those based on
      mechanical energy. Metabolic energy approaches share the perspective that
      prediction of locomotor energy expenditure should be based on statistically
      significant proxies of metabolic function, while mechanical energy approaches,
      which derive from many different perspectives, focus on quantifying the energy of
      movement. Some controversy exists as to which mechanical perspective is "best",
      but from first principles all mechanical methods should be equivalent if the
      inputs to the simulation are of similar quality. Our goals in this paper are 1)
      to establish the degree to which the various methods of calculating mechanical
      energy are correlated, and 2) to investigate to what degree the prediction
      methods explain the variation in energy expenditure. METHODOLOGY/PRINCIPAL
      FINDINGS: We use modern humans as the model organism in this experiment because
      their data are readily attainable, but the methodology is appropriate for use in
      other species. Volumetric oxygen consumption and kinematic and kinetic data were
      collected on 8 adults while walking at their self-selected slow, normal and fast
      velocities. Using hierarchical statistical modeling via ordinary least squares
      and maximum likelihood techniques, the predictive ability of several metabolic
      and mechanical approaches were assessed. We found that all approaches are
      correlated and that the mechanical approaches explain similar amounts of the
      variation in metabolic energy expenditure. Most methods predict the variation
      within an individual well, but are poor at accounting for variation between
      individuals. CONCLUSION: Our results indicate that the choice of predictive
      method is dependent on the question(s) of interest and the data available for use
      as inputs. Although we used modern humans as our model organism, these results
      can be extended to other species.

PMID- 21731694
TI  - Control of centrin stability by Aurora A.
AB  - Aurora A is an oncogenic serine/threonine kinase which can cause cell
      transformation and centrosome amplification when over-expressed. Human breast
      tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here,
      we show that Aurora A mediates the phosphorylation of and localizes with centrin
      at the centrosome, with both proteins reaching maximum abundance from prophase
      through metaphase, followed by their precipitous loss in late stages of mitosis.
      Over-expression of Aurora A results in excess phospho-centrin and centrosome
      amplification. In contrast, centrosome amplification is not seen in cells over
      expressing Aurora A in the presence of a recombinant centrin mutant lacking the
      serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A
      results in a decrease in mitotic index and abrogation of centrin phosphorylation.
      Finally, a recombinant centrin mutation that mimics centrin phosphorylation
      increases centrin's stability against APC/C-mediated proteasomal degradation.
      Taken together, these results suggest that the stability of centrin is regulated
      in part by Aurora A, and that excess phosphorylated centrin may promote
      centrosome amplification in cancer.

PMID- 21731695
TI  - Genome sequencing reveals unique mutations in characteristic metabolic pathways
      and the transfer of virulence genes between V. mimicus and V. cholerae.
AB  - Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in
      the natural environmental and sometimes causes diarrhea and internal infections
      in humans. It shows similar phenotypes to V. cholerae but differs in some
      biochemical characteristics. The molecular mechanisms underlying the differences
      in biochemical metabolism between V. mimicus and V. cholerae are currently
      unclear. Several V. mimicus isolates have been found that carry cholera toxin
      genes (ctxAB) and cause cholera-like diarrhea in humans. Here, the genome of the
      V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and
      annotated. Analysis of its genome, together with those of other Vibrio species,
      revealed extensive differences within the Vibrionaceae. Common mutations in gene
      clusters involved in three biochemical metabolism pathways that are used for
      discrimination between V. mimicus and V. cholerae were found in V. mimicus
      strains. We also constructed detailed genomic structures and evolution maps for
      the general types of genomic drift associated with pathogenic characters in
      polysaccharides, CTX elements and toxin co-regulated pilus (TCP) gene clusters.
      Overall, the whole-genome sequencing of the V. mimicus strain carrying the
      cholera toxin gene provides detailed information for understanding genomic
      differences among Vibrio spp. V. mimicus has a large number of diverse gene and
      nucleotide differences from its nearest neighbor, V. cholerae. The observed
      mutations in the characteristic metabolism pathways may indicate different
      adaptations to different niches for these species and may be caused by ancient
      events in evolution before the divergence of V. cholerae and V. mimicus.
      Horizontal transfers of virulence-related genes from an uncommon clone of V.
      cholerae, rather than the seventh pandemic strains, have generated the pathogenic
      V. mimicus strain carrying cholera toxin genes.

PMID- 21731696
TI  - MicroRNA expression and clinical outcome of small cell lung cancer.
AB  - The role of microRNAs in small-cell lung carcinoma (SCLC) is largely unknown. miR
      34a is known as a p53 regulated tumor suppressor microRNA in many cancer types.
      However, its therapeutic implication has never been studied in SCLC, a cancer
      type with frequent dysfunction of p53. We investigated the expression of a panel
      of 7 microRNAs (miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a) in 31 SCLC
      tumors, 14 SCLC cell lines, and 26 NSCLC cell lines. We observed significantly
      lower miR-21, miR-29b, and miR-34a expression in SCLC cell lines than in NSCLC
      cell lines. The expression of the 7 microRNAs was unrelated to SCLC patients'
      clinical characteristics and was neither prognostic in term of overall survival
      or progression-free survival nor predictive of treatment response. Overexpression
      or downregulation of miR-34a did not influence SCLC cell viability. The
      expression of these 7 microRNAs also did not predict in vitro sensitivity to
      cisplatin or etoposide in SCLC cell lines. Overexpression or downregulation of
      miR-34a did not influence sensitivity to cisplatin or etoposide in SCLC cell
      lines. In contrast to downregulation of the miR-34a target genes cMET and Axl by
      overexpression of miR-34a in NSCLC cell lines, the intrinsic expression of cMET
      and Axl was low in SCLC cell lines and was not influenced by overexpression of
      miR-34a. Our results suggest that the expression of the 7 selected microRNAs are
      not prognostic in SCLC patients, and miR-34a is unrelated to the malignant
      behavior of SCLC cells and is unlikely to be a therapeutic target.

PMID- 21731697
TI  - Quantitation of cellular dynamics in growing Arabidopsis roots with light sheet
      microscopy.
AB  - To understand dynamic developmental processes, living tissues have to be imaged
      frequently and for extended periods of time. Root development is extensively
      studied at cellular resolution to understand basic mechanisms underlying pattern
      formation and maintenance in plants. Unfortunately, ensuring continuous specimen
      access, while preserving physiological conditions and preventing photo-damage,
      poses major barriers to measurements of cellular dynamics in growing organs such
      as plant roots. We present a system that integrates optical sectioning through
      light sheet fluorescence microscopy with hydroponic culture that enables us to
      image, at cellular resolution, a vertically growing Arabidopsis root every few
      minutes and for several consecutive days. We describe novel automated routines to
      track the root tip as it grows, to track cellular nuclei and to identify cell
      divisions. We demonstrate the system's capabilities by collecting data on
      divisions and nuclear dynamics.

PMID- 21731698
TI  - Genome-wide profiling of microRNAs in adipose mesenchymal stem cell
      differentiation and mouse models of obesity.
AB  - In recent years, there has been accumulating evidence that microRNAs are key
      regulator molecules of gene expression. The cellular processes that are regulated
      by microRNAs include e.g. cell proliferation, programmed cell death and cell
      differentiation. Adipocyte differentiation is a highly regulated cellular process
      for which several important regulating factors have been discovered, but still
      not all are known to fully understand the underlying mechanisms. In the present
      study, we analyzed the expression of 597 microRNAs during the differentiation of
      mouse mesenchymal stem cells into terminally differentiated adipocytes by real
      time RT-PCR. In total, 66 miRNAs were differentially expressed in mesenchymal
      stem cell-derived adipocytes compared to the undifferentiated progenitor cells.
      To further study the regulation of these 66 miRNAs in white adipose tissue in
      vivo and their dependence on PPARgamma activity, mouse models of genetically or
      diet induced obesity as well as a mouse line expressing a dominant negative
      PPARgamma mutant were employed.

PMID- 21731699
TI  - Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain.
AB  - Recent discovery of 5-hydroxymethylcytosine (5hmC) in genomic DNA raises the
      question how this sixth base is recognized by cellular proteins. In contrast to
      the methyl-CpG binding domain (MBD) of MeCP2, we found that the SRA domain of
      Uhrf1, an essential factor in DNA maintenance methylation, binds 5hmC and 5
      methylcytosine containing substrates with similar affinity. Based on the co
      crystal structure, we performed molecular dynamics simulations of the SRA:DNA
      complex with the flipped cytosine base carrying either of these epigenetic
      modifications. Our data indicate that the SRA binding pocket can accommodate 5hmC
      and stabilizes the flipped base by hydrogen bond formation with the hydroxyl
      group.

PMID- 21731700
TI  - The comparative osteology of the petrotympanic complex (ear region) of extant
      baleen whales (Cetacea: Mysticeti).
AB  - BACKGROUND: Anatomical comparisons of the ear region of baleen whales (Mysticeti)
      are provided through detailed osteological descriptions and high-resolution
      photographs of the petrotympanic complex (tympanic bulla and petrosal bone) of
      all extant species of mysticete cetaceans. Salient morphological features are
      illustrated and identified, including overall shape of the bulla, size of the
      conical process of the bulla, morphology of the promontorium, and the size and
      shape of the anterior process of the petrosal. We place our comparative
      osteological observations into a phylogenetic context in order to initiate an
      exploration into petrotympanic evolution within Mysticeti. PRINCIPAL FINDINGS:
      The morphology of the petrotympanic complex is diagnostic for individual species
      of baleen whale (e.g., sigmoid and conical processes positioned at midline of
      bulla in Balaenoptera musculus; confluence of fenestra cochleae and perilymphatic
      foramen in Eschrichtius robustus), and several mysticete clades are united by
      derived characteristics. Balaenids and neobalaenids share derived features of the
      bulla, such as a rhomboid shape and a reduced anterior lobe (swelling) in ventral
      aspect, and eschrichtiids share derived morphologies of the petrosal with
      balaenopterids, including loss of a medial promontory groove and dorsomedial
      elongation of the promontorium. Monophyly of Balaenoidea (Balaenidae and
      Neobalaenidae) and Balaenopteroidea (Balaenopteridae and Eschrichtiidae) was
      recovered in phylogenetic analyses utilizing data exclusively from the
      petrotympanic complex. SIGNIFICANCE: This study fills a major gap in our
      knowledge of the complex structures of the mysticete petrotympanic complex, which
      is an important anatomical region for the interpretation of the evolutionary
      history of mammals. In addition, we introduce a novel body of phylogenetically
      informative characters from the ear region of mysticetes. Our detailed anatomical
      descriptions, illustrations, and comparisons provide valuable data for current
      and future studies on the phylogenetic relationships, evolution, and auditory
      physiology of mysticetes and other cetaceans throughout Earth's history.

PMID- 21731701
TI  - Functional role of dimerization of human peptidylarginine deiminase 4 (PAD4).
AB  - Peptidylarginine deiminase 4 (PAD4) is a homodimeric enzyme that catalyzes Ca2+
      dependent protein citrullination, which results in the conversion of arginine to
      citrulline. This paper demonstrates the functional role of dimerization in the
      regulation of PAD4 activity. To address this question, we created a series of
      dimer interface mutants of PAD4. The residues Arg8, Tyr237, Asp273, Glu281,
      Tyr435, Arg544 and Asp547, which are located at the dimer interface, were mutated
      to disturb the dimer organization of PAD4. Sedimentation velocity experiments
      were performed to investigate the changes in the quaternary structures and the
      dissociation constants (K(d)) between wild-type and mutant PAD4 monomers and
      dimers. The kinetic data indicated that disrupting the dimer interface of the
      enzyme decreases its enzymatic activity and calcium-binding cooperativity. The
      K(d) values of some PAD4 mutants were much higher than that of the wild-type (WT)
      protein (0.45 uM) and were concomitant with lower k(cat) values than that of WT
      (13.4 s-1). The K(d) values of the monomeric PAD4 mutants ranged from 16.8 to
      45.6 uM, and the k(cat) values of the monomeric mutants ranged from 3.3 to 7.3 s
      1. The k(cat) values of these interface mutants decreased as the K(d) values
      increased, which suggests that the dissociation of dimers to monomers
      considerably influences the activity of the enzyme. Although dissociation of the
      enzyme reduces the activity of the enzyme, monomeric PAD4 is still active but
      does not display cooperative calcium binding. The ionic interaction between Arg8
      and Asp547 and the Tyr435-mediated hydrophobic interaction are determinants of
      PAD4 dimer formation.

PMID- 21731702
TI  - Intuitive visualization and analysis of multi-omics data and application to
      Escherichia coli carbon metabolism.
AB  - Combinations of 'omics' investigations (i.e, transcriptomic, proteomic,
      metabolomic and/or fluxomic) are increasingly applied to get comprehensive
      understanding of biological systems. Because the latter are organized as complex
      networks of molecular and functional interactions, the intuitive interpretation
      of multi-omics datasets is difficult. Here we describe a simple strategy to
      visualize and analyze multi-omics data. Graphical representations of complex
      biological networks can be generated using Cytoscape where all molecular and
      functional components could be explicitly represented using a set of dedicated
      symbols. This representation can be used i) to compile all biologically-relevant
      information regarding the network through web link association, and ii) to map
      the network components with multi-omics data. A Cytoscape plugin was developed to
      increase the possibilities of both multi-omic data representation and
      interpretation. This plugin allowed different adjustable colour scales to be
      applied to the various omics data and performed the automatic extraction and
      visualization of the most significant changes in the datasets. For illustration
      purpose, the approach was applied to the central carbon metabolism of Escherichia
      coli. The obtained network contained 774 components and 1232 interactions,
      highlighting the complexity of bacterial multi-level regulations. The structured
      representation of this network represents a valuable resource for systemic
      studies of E. coli, as illustrated from the application to multi-omics data. Some
      current issues in network representation are discussed on the basis of this work.

PMID- 21731703
TI  - Role of TMPRSS2-ERG gene fusion in negative regulation of PSMA expression.
AB  - Prostate specific membrane antigen (PSMA) is overexpressed in prostatic
      adenocarcinoma (CaP), and its expression is negatively regulated by androgen
      stimulation. However, it is still unclear which factors are involved in this
      downregulation. TMPRSS2-ERG fusion is the most common known gene rearrangement in
      prostate carcinoma. Androgen stimulation can increase expression of the TMPRSS2
      ERG fusion in fusion positive prostate cancer cells. The purpose of this
      investigation is to determine whether PSMA expression can be regulated by the
      TMPRSS2-ERG gene fusion. We employed two PSMA positive cell lines: VCaP cells,
      which harbor TMPRSS2-ERG fusion, and LNCaP cells, which lack the fusion. After 24
      hours of androgen treatment, TMPRSS2-ERG mRNA level was increased in VCaP cells.
      PSMA mRNA level was dramatically decreased in VCaP cells, while it only has
      moderate change in LNCaP cells. Treatment with the androgen antagonist flutamide
      partially restored PSMA expression in androgen-treated VCaP cells. Knocking down
      ERG by siRNA in VCaP cells enhances PSMA expression both in the presence and
      absence of synthetic androgen R1881. Overexpressing TMPRSS2-ERG fusions in LNCaP
      cells downregulated PSMA both in the presence or absence of R1881, while
      overexpressing wild type ERG did not. Using PSMA-based luciferase reporter
      assays, we found TMPRSS2-ERG fusion can inhibit PSMA activity at the
      transcriptional level. Our data indicated that downregulation of PSMA in androgen
      treated VCaP cells appears partially mediated by TMPRSS2-ERG gene fusion.

PMID- 21731704
TI  - Pharmacological characterization of [3H]CHIBA-3007 binding to glycine transporter
      1 in the rat brain.
AB  - Glycine transporter-1 (GlyT-1) in glial cells regulates extracellular levels of
      glycine, which acts as an obligatory co-agonist at the N-methyl-D-aspartate
      (NMDA) receptors in the brain. In the present study, we developed a novel
      radioligand, [3H]3-chloro-N-((S)-((R)-1-methylpiperidin-2-yl)(thiophen- 3
      yl)methyl)-4- (trifluoromethyl)picolinamide ([3H]CHIBA-3007), for studying GlyT-1
      in the brain. The presence of a single saturable high-affinity binding component
      for [3H]CHIBA-3007 binding to the rat brain membranes was detected. Scatchard
      analysis revealed an apparent equilibrium dissociation constant (K(d)) of 1.61+/
      0.16 nM and a maximal number of binding sites (B(max)) of 692.8+/-22.8 fmol/mg
      protein (mean +/- SEM, n = 3). The specific binding of [3H]CHIBA-3007 was
      inhibited by a number of GlyT-1 inhibitors, such as CHIBA-3007, desmethyl-CHIBA
      3007, CHIBA-3008, SSR504734, NFPS/ALX5407, LY2365109 and Org24598, consistent
      with the pharmacological profiles of GlyT-1 inhibitors. Interestingly, the
      potency of eight GlyT-1 inhibitors (CHIBA-3007, desmethyl-CHIBA-3007,
      NFPS/ALX5407, LY2365109, Org24598, SSR504734, sarcosine, and glycine) for
      blocking in vitro specific binding of [3H]CHIBA-3007 was significantly correlated
      with the potency of these inhibitors for inhibiting [14C]glycine uptake in the
      rat brain membranes. In contrast, the GlyT-2 inhibitor ALX1393 exhibited very
      weak for [3H]CHIBA-3007 binding. Furthermore, the regional distribution of
      [3H]CHIBA-3007 binding in the rat brain was similar to the previously reported
      distribution of GlyT-1. The present findings suggest that [3H]CHIBA-3007 would be
      a useful new radioligand for studying GlyT-1 in the brain.

PMID- 21731705
TI  - A minimal model for the mitochondrial rapid mode of Ca2+ uptake mechanism.
AB  - Mitochondria possess a remarkable ability to rapidly accumulate and sequester
      Ca2+. One of the mechanisms responsible for this ability is believed to be the
      rapid mode (RaM) of Ca2+ uptake. Despite the existence of many models of
      mitochondrial Ca2+ dynamics, very few consider RaM as a potential mechanism that
      regulates mitochondrial Ca2+ dynamics. To fill this gap, a novel mathematical
      model of the RaM mechanism is developed herein. The model is able to simulate the
      available experimental data of rapid Ca2+ uptake in isolated mitochondria from
      both chicken heart and rat liver tissues with good fidelity. The mechanism is
      based on Ca2+ binding to an external trigger site(s) and initiating a brief
      transient of high Ca2+ conductivity. It then quickly switches to an inhibited,
      zero-conductive state until the external Ca2+ level is dropped below a critical
      value (~100-150 nM). RaM's Ca2+- and time-dependent properties make it a unique
      Ca2+ transporter that may be an important means by which mitochondria take up
      Ca2+ in situ and help enable mitochondria to decode cytosolic Ca2+ signals.
      Integrating the developed RaM model into existing models of mitochondrial Ca2+
      dynamics will help elucidate the physiological role that this unique mechanism
      plays in mitochondrial Ca2+-homeostasis and bioenergetics.

PMID- 21731706
TI  - Regulation of gene expression in plants through miRNA inactivation.
AB  - Eukaryotic organisms possess a complex RNA-directed gene expression regulatory
      network allowing the production of unique gene expression patterns. A recent
      addition to the repertoire of RNA-based gene regulation is miRNA target decoys,
      endogenous RNA that can negatively regulate miRNA activity. miRNA decoys have
      been shown to be a valuable tool for understanding the function of several miRNA
      families in plants and invertebrates. Engineering and precise manipulation of an
      endogenous RNA regulatory network through modification of miRNA activity also
      affords a significant opportunity to achieve a desired outcome of enhanced plant
      development or response to environmental stresses. Here we report that expression
      of miRNA decoys as single or heteromeric non-cleavable microRNA (miRNA) sites
      embedded in either non-protein-coding or within the 3' untranslated region of
      protein-coding transcripts can regulate the expression of one or more miRNA
      targets. By altering the sequence of the miRNA decoy sites, we were able to
      attenuate miRNA inactivation, which allowed for fine regulation of native miRNA
      targets and the production of a desirable range of plant phenotypes. Thus, our
      results demonstrate miRNA decoys are a flexible and robust tool, not only for
      studying miRNA function, but also for targeted engineering of gene expression in
      plants. Computational analysis of the Arabidopsis transcriptome revealed a number
      of potential miRNA decoys, suggesting that endogenous decoys may have an
      important role in natural modulation of expression in plants.

PMID- 21731707
TI  - Transcriptional activation of TINF2, a gene encoding the telomere-associated
      protein TIN2, by Sp1 and NF-kappaB factors.
AB  - The expression of the telomere-associated protein TIN2 has been shown to be
      essential for early embryonic development in mice and for development of a
      variety of human malignancies. Recently, germ-line mutations in TINF2, which
      encodes for the TIN2 protein, have been identified in a number of patients with
      bone-marrow failure syndromes. Yet, the molecular mechanisms that regulate TINF2
      expression are largely unknown. To elucidate the mechanisms involved in human
      TINF2 regulation, we cloned a 2.7 kb genomic DNA fragment containing the putative
      promoter region and, through deletion analysis, identified a 406 bp region that
      functions as a minimal promoter. This promoter proximal region is predicted to
      contain several putative Sp1 and NF-kappaB binding sites based on bioinformatic
      analysis. Direct binding of the Sp1 and NF-kappaB transcription factors to the
      TIN2 promoter sequence was demonstrated by electrophoretic mobility shift assay
      (EMSA) and/or chromatin immunoprecipitation (ChIP) assays. Transfection of a
      plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells
      strongly activated TIN2 promoter-driven luciferase reporter expression.
      Similarly, the NF-kappaB molecules p50 and p65 were found to strongly activate
      luciferase expression in NF-kappaB knockout MEFs. Mutating the predicted
      transcription factor binding sites effectively reduced TIN2 promoter activity.
      Various known chemical inhibitors of Sp1 and NF-kappaB could also strongly
      inhibit TIN2 transcriptional activity. Collectively, our results demonstrate the
      important roles that Sp1 and NF-kappaB play in regulating the expression of the
      human telomere-binding protein TIN2, which can shed important light on its
      possible role in causing various forms of human diseases and cancers.

PMID- 21731708
TI  - Self-collected mid-turbinate swabs for the detection of respiratory viruses in
      adults with acute respiratory illnesses.
AB  - BACKGROUND: The gold standard for respiratory virus testing is a nasopharyngeal
      (NP) swab, which is collected by a healthcare worker. Midturbinate (MT) swabs are
      an alternative due to their ease of collection and possible self-collection by
      patients. The objective of this study was to compare the respiratory virus
      isolation of flocked MT swabs compared to flocked NP swabs. METHODS: Beginning in
      October 2008, healthy adults aged 18 to 69 years were recruited into a cohort and
      followed up for symptoms of influenza. They were asked to have NP and MT swabs
      taken as soon as possible after the onset of a fever or two or more respiratory
      symptoms with an acute onset. The swabs were tested for viral respiratory
      infections using Seeplex(r) RV12 multiplex PCR detection kit. Seventy six pairs
      of simultaneous NP and MT swabs were collected from 38 symptomatic subjects.
      Twenty nine (38%) of these pairs were positive by either NP or MT swabs or both.
      Sixty nine (91%) of the pair results were concordant. Two samples (3%) for hCV
      OC43/HKU1 and 1 sample (1%) for rhinovirus A/B were positive by NP but negative
      by MT. One sample each for hCV 229E/NL63, hCV OC43/HKU1, respiratory syncytial
      virus A, and influenza B were positive by MT but negative by NP. CONCLUSIONS:
      Flocked MT swabs are sensitive for the diagnosis of multiple respiratory viruses.
      Given the ease of MT collection and similar results between the two swabs, it is
      likely that MT swabs should be the preferred method of respiratory cell
      collection for outpatient studies. In light of this data, larger studies should
      be performed to ensure that this still holds true and data should also be
      collected on the patient preference of collection methods.

PMID- 21731709
TI  - Insulin-regulated Srebp-1c and Pck1 mRNA expression in primary hepatocytes from
      zucker fatty but not lean rats is affected by feeding conditions.
AB  - Insulin regulates the transcription of genes for hepatic glucose and lipid
      metabolism. We hypothesized that this action may be impaired in hepatocytes from
      insulin resistant animals. Primary hepatocytes from insulin sensitive Zucker lean
      (ZL) and insulin resistant Zucker fatty (ZF) rats in ad libitum or after an
      overnight fasting were isolated, cultured and treated with insulin and other
      compounds for analysis of gene expression using real-time PCR. The mRNA levels of
      one insulin-induced (Srebp-1c) and one insulin-suppressed (Pck1) genes in
      response to insulin, glucagon, and compactin treatments in hepatocytes from ad
      libitum ZL and ZF rats were analyzed. Additionally, the effects of insulin and
      T1317 on their levels in hepatocytes from ad libitum or fasted ZL or ZF rats were
      compared. The mRNA levels of Srebp-1c, Fas, and Scd1, but not that of Insr, Gck
      and Pck1, were higher in freshly isolated hepatocytes from ad libitum ZF than
      that from ZL rats. These patterns of Srebp-1c and Pck1 mRNA levels remained in
      primary hepatocyte cultured in vitro. Insulin's ability to regulate Srebp-1c and
      Pck1 expression was diminished in hepatocytes from ad libitum ZF, but not ZL
      rats. Glucagon or compactin suppressed Srebp-1c mRNA expression in lean, but not
      fatty hepatocytes. However, glucagon induced Pck1 mRNA expression similarly in
      hepatocytes from ad libitum ZL and ZF rats. Insulin caused the same dose
      dependent increase of Akt phosphorylation in hepatocytes from ad libitum ZL and
      ZF rats. It synergized with T1317 to induce Srebp-1c, and suppressed Pck1 mRNA
      levels in hepatocytes from fasted, but not that from ad libitum ZF rats. We
      demonstrated that insulin was unable to regulate its downstream genes' mRNA
      expression in hepatocytes from ad libitum ZF rats. This impairment can be
      partially restored in hepatocytes from ZF rats after an overnight fasting, a
      phenomenon that deserves further investigation.

PMID- 21731710
TI  - Mitochondrial oxidative phosphorylation compensation may preserve vision in
      patients with OPA1-linked autosomal dominant optic atrophy.
AB  - Autosomal Dominant Optic Atrophy (ADOA) is the most common inherited optic
      atrophy where vision impairment results from specific loss of retinal ganglion
      cells of the optic nerve. Around 60% of ADOA cases are linked to mutations in the
      OPA1 gene. OPA1 is a fission-fusion protein involved in mitochondrial inner
      membrane remodelling. ADOA presents with marked variation in clinical phenotype
      and varying degrees of vision loss, even among siblings carrying identical
      mutations in OPA1. To determine whether the degree of vision loss is associated
      with the level of mitochondrial impairment, we examined mitochondrial function in
      lymphoblast cell lines obtained from six large Australian OPA1-linked ADOA
      pedigrees. Comparing patients with severe vision loss (visual acuity [VA]<6/36)
      and patients with relatively preserved vision (VA>6/9) a clear defect in
      mitochondrial ATP synthesis and reduced respiration rates were observed in
      patients with poor vision. In addition, oxidative phosphorylation (OXPHOS)
      enzymology in ADOA patients with normal vision revealed increased complex II+III
      activity and levels of complex IV protein. These data suggest that OPA1
      deficiency impairs OXPHOS efficiency, but compensation through increases in the
      distal complexes of the respiratory chain may preserve mitochondrial ATP
      production in patients who maintain normal vision. Identification of genetic
      variants that enable this response may provide novel therapeutic insights into
      OXPHOS compensation for preventing vision loss in optic neuropathies.

PMID- 21731711
TI  - Redundant mechanisms prevent mitotic entry following replication arrest in the
      absence of Cdc25 hyper-phosphorylation in fission yeast.
AB  - Following replication arrest the Cdc25 phosphatase is phosphorylated and
      inhibited by Cds1. It has previously been reported that expressing Cdc25 where 9
      putative amino-terminal Cds1 phosphorylation sites have been substituted to
      alanine results in bypass of the DNA replication checkpoint. However, these
      results were acquired by expression of the phosphorylation mutant using a
      multicopy expression vector in a genetic background where the DNA replication
      checkpoint is intact. In order to clarify these results we constructed a
      Cdc25(9A)-GFP native promoter integrant and examined its effect on the
      replication checkpoint at endogenous expression levels. In this strain the
      replication checkpoint operates normally, conditional on the presence of the Mik1
      kinase. In response to replication arrest the Cdc25(9A)-GFP protein is degraded,
      suggesting the presence of a backup mechanism to eliminate the phosphatase when
      it cannot be inhibited through phosphorylation.

PMID- 21731712
TI  - Differentiation and glucocorticoid regulated apopto-phagocytic gene expression
      patterns in human macrophages. Role of Mertk in enhanced phagocytosis.
AB  - The daily clearance of physiologically dying cells is performed safely mainly by
      cells in the mononuclear phagocyte system. They can recognize and engulf dying
      cells utilizing several cooperative mechanisms. In our study we show that the
      expression of a broad range of apopto-phagocytic genes is strongly up-regulated
      during differentiation of human monocytes to macrophages with different donor
      variability. The glucocorticoid dexamethasone has a profound effect on this
      process by selectively up-regulating six genes and down-regulating several
      others. The key role of the up-regulated mer tyrosine kinase (Mertk) in
      dexamethasone induced enhancement of phagocytosis could be demonstrated in human
      monocyte derived macrophages by gene silencing as well as blocking antibodies,
      and also in a monocyte-macrophage like cell line. However, the additional role of
      other glucocorticoid induced elements must be also considered since the presence
      of autologous serum during phagocytosis could almost completely compensate for
      the blocked function of Mertk.

PMID- 21731713
TI  - Thyroid hormone signalling genes are regulated by photoperiod in the hypothalamus
      of F344 rats.
AB  - Seasonal animals adapt their physiology and behaviour in anticipation of climate
      change to optimise survival of their offspring. Intra-hypothalamic thyroid
      hormone signalling plays an important role in seasonal responses in mammals and
      birds. In the F344 rat, photoperiod stimulates profound changes in food intake,
      body weight and reproductive status. Previous investigations of the F344 rat have
      suggested a role for thyroid hormone metabolism, but have only considered Dio2
      expression, which was elevated in long day photoperiods. Microarray analysis was
      used to identify time-dependent changes in photoperiod responsive genes, which
      may underlie the photoperiod-dependent phenotypes of the juvenile F344 rat. The
      most significant changes are those related to thyroid hormone metabolism and
      transport. Using photoperiod manipulations and melatonin injections into long day
      photoperiod (LD) rats to mimic short day (SD), we show photoinduction and
      photosuppression gene expression profiles and melatonin responsiveness of genes
      by in situ hybridization; TSHbeta, CGA, Dio2 and Oatp1c1 genes were all elevated
      in LD whilst in SD, Dio3 and MCT-8 mRNA were increased. NPY was elevated in SD
      whilst GALP increased in LD. The photoinduction and photosuppression profiles for
      GALP were compared to that of GHRH with GALP expression following GHRH
      temporally. We also reveal gene sets involved in photoperiodic responses,
      including retinoic acid and Wnt/beta-catenin signalling. This study extends our
      knowledge of hypothalamic regulation by photoperiod, by revealing large temporal
      changes in expression of thyroid hormone signalling genes following photoperiod
      switch. Surprisingly, large changes in hypothalamic thyroid hormone levels or TRH
      expression were not detected. Expression of NPY and GALP, two genes known to
      regulate GHRH, were also changed by photoperiod. Whether these genes could
      provide links between thyroid hormone signalling and the regulation of the growth
      axis remains to be investigated.

PMID- 21731714
TI  - Short-term serum-free culture reveals that inhibition of Gsk3beta induces the
      tumor-like growth of mouse embryonic stem cells.
AB  - Here, we present evidence that the tumor-like growth of mouse embryonic stem
      cells (mESCs) is suppressed by short-term serum-free culture, which is reversed
      by pharmacological inhibition of Gsk3beta. Mouse ESCs maintained under standard
      conditions using fetal bovine serum (FBS) were cultured in a uniquely formulated
      chemically-defined serum-free (CDSF) medium, namely ESF7, for three passages
      before being subcutaneously transplanted into immunocompromised mice.
      Surprisingly, the mESCs failed to produce teratomas for up to six months, whereas
      mESCs maintained under standard conditions generated well-developed teratomas in
      five weeks. Mouse ESCs cultured under CDSF conditions maintained the expression
      of Oct3/4, Nanog, Sox2 and SSEA1, and differentiated into germ cells in vivo. In
      addition, when mESCs were cultured under CDSF conditions supplemented with FBS,
      or when the cells were cultured under CDSF conditions followed by standard
      culture conditions, they consistently developed into teratomas. Thus, these
      results validate that the pluripotency of mESCs was not compromised by CDSF
      conditions. Mouse ESCs cultured under CDSF conditions proliferated significantly
      more slowly than mESCs cultured under standard conditions, and were reminiscent
      of Eras-null mESCs. In fact, their slower proliferation was accompanied by the
      downregulation of Eras and c-Myc, which regulate the tumor-like growth of mESCs.
      Remarkably, when mESCs were cultured under CDSF conditions supplemented with a
      pharmacological inhibitor of Gsk3beta, they efficiently proliferated and
      developed into teratomas without upregulation of Eras and c-Myc, whereas mESCs
      cultured under standard conditions expressed Eras and c-Myc. Although the role of
      Gsk3beta in the self-renewal of ESCs has been established, it is suggested with
      these data that Gsk3beta governs the tumor-like growth of mESCs by means of a
      mechanism different from the one to support the pluripotency of ESCs.

PMID- 21731715
TI  - Intrapopulation variability shaping isotope discrimination and turnover:
      experimental evidence in arctic foxes.
AB  - BACKGROUND: Tissue-specific stable isotope signatures can provide insights into
      the trophic ecology of consumers and their roles in food webs. Two parameters are
      central for making valid inferences based on stable isotopes, isotopic
      discrimination (difference in isotopic ratio between consumer and its diet) and
      turnover time (renewal process of molecules in a given tissue usually measured
      when half of the tissue composition has changed). We investigated simultaneously
      the effects of age, sex, and diet types on the variation of discrimination and
      half-life in nitrogen and carbon stable isotopes (delta15N and delta13C,
      respectively) in five tissues (blood cells, plasma, muscle, liver, nail, and
      hair) of a top predator, the arctic fox Vulpes lagopus. METHODOLOGY/PRINCIPAL
      FINDINGS: We fed 40 farmed foxes (equal numbers of adults and yearlings of both
      sexes) with diet capturing the range of resources used by their wild
      counterparts. We found that, for a single species, six tissues, and three diet
      types, the range of discrimination values can be almost as large as what is known
      at the scale of the whole mammalian or avian class. Discrimination varied
      depending on sex, age, tissue, and diet types, ranging from 0.30/00 to 5.30/00
      (mean  = 2.60/00) for delta15N and from 0.20/00 to 2.90/00 (mean  = 0.90/00) for
      delta13C. We also found an impact of population structure on delta15N half-life
      in blood cells. Varying across individuals, delta15N half-life in plasma (6 to 10
      days) was also shorter than for delta13C (14 to 22 days), though delta15N and
      delta13C half-lives are usually considered as equal. CONCLUSION/SIGNIFICANCE:
      Overall, our multi-factorial experiment revealed that at least six levels of
      isotopic variations could co-occur in the same population. Our experimental
      analysis provides a framework for quantifying multiple sources of variation in
      isotopic discrimination and half-life that needs to be taken into account when
      designing and analysing ecological field studies.

PMID- 21731716
TI  - Continued stabilization of the nuclear higher-order structure of post-mitotic
      neurons in vivo.
AB  - BACKGROUND: Cellular terminal differentiation (TD) correlates with a permanent
      exit from the cell cycle and so TD cells become stably post-mitotic. However, TD
      cells express the molecular machinery necessary for cell proliferation that can
      be reactivated by experimental manipulation, yet it has not been reported the
      stable proliferation of any type of reactivated TD cells. Neurons become post
      mitotic after leaving the ventricular zone. When neurons are forced to reenter
      the cell cycle they invariably undergo cell death. Wider evidence indicates that
      the post-mitotic state cannot solely depend on gene products acting in trans,
      otherwise mutations in the corresponding genes may lead to reentry and completion
      of the cell cycle in TD cells, but this has not been observed. In the interphase,
      nuclear DNA of metazoan cells is organized in supercoiled loops anchored to a
      nuclear nuclear matrix (NM). The DNA-NM interactions define a higher-order
      structure in the cell nucleus (NHOS). We have previously compared the NHOS of
      aged rat hepatocytes with that of early post-mitotic rat neurons and our results
      indicated that a very stable NHOS is a common feature of both senescent and post
      mitotic cells in vivo. PRINCIPAL FINDINGS: In the present work we compared the
      NHOS in rat neurons from different post-natal ages. Our results show that the
      trend towards further stabilization of the NHOS in neurons continues throughout
      post-natal life. This phenomenon occurs in absence of overt changes in the post
      mitotic state and transcriptional activity of neurons, suggesting that it is
      independent of functional constraints. CONCLUSIONS: Apparently the continued
      stabilization of the NHOS as a function of time is basically determined by
      thermodynamic and structural constraints. We discuss how the resulting highly
      stable NHOS of neurons may be the structural, non-genetic basis of their
      permanent and irreversible post-mitotic state.

PMID- 21731717
TI  - Contribution of pollinator-mediated crops to nutrients in the human food supply.
AB  - The contribution of nutrients from animal pollinated world crops has not
      previously been evaluated as a biophysical measure for the value of pollination
      services. This study evaluates the nutritional composition of animal-pollinated
      world crops. We calculated pollinator dependent and independent proportions of
      different nutrients of world crops, employing FAO data for crop production, USDA
      data for nutritional composition, and pollinator dependency data according to
      Klein et al. (2007). Crop plants that depend fully or partially on animal
      pollinators contain more than 90% of vitamin C, the whole quantity of Lycopene
      and almost the full quantity of the antioxidants beta-cryptoxanthin and beta
      tocopherol, the majority of the lipid, vitamin A and related carotenoids, calcium
      and fluoride, and a large portion of folic acid. Ongoing pollinator decline may
      thus exacerbate current difficulties of providing a nutritionally adequate diet
      for the global human population.

PMID- 21731718
TI  - Evidence of distinct tumour-propagating cell populations with different
      properties in primary human hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: Increasing evidence that a number of malignancies are
      characterised by tumour cell heterogeneity has recently been published, but there
      is still a lack of data concerning liver cancers. The aim of this study was to
      investigate and characterise tumour-propagating cell (TPC) compartments within
      human hepatocellular carcinoma (HCC). METHODS: After long-term culture, we
      identified three morphologically different tumour cell populations in a single
      HCC specimen, and extensively characterised them by means of flow cytometry,
      fluorescence microscopy, karyotyping and microarray analyses, single cell
      cloning, and xenotransplantation in NOD/SCID/IL2Rgamma/- mice. RESULTS: The
      primary cell populations (hcc-1, -2 and -3) and two clones generated by means of
      limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed a number
      of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133,
      CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug
      resistance and tumorigenic potential. Moreover, we found that ALDH expression, in
      combination with CD44 or Thy-1 negativity or CD56 positivity identified
      subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3
      primary cell populations, respectively. Karyotyping revealed the clonal evolution
      of the cell populations and clones within the primary tumour. Importantly, the
      primary tumour cell population with the greatest tumorigenic potential and drug
      resistance showed more chromosomal alterations than the others and contained
      clones with epithelial and mesenchymal features. CONCLUSIONS: Individual HCCs can
      harbor different self-renewing tumorigenic cell types expressing a variety of
      morphological and phenotypical markers, karyotypic evolution and different gene
      expression profiles. This suggests that the models of hepatic carcinogenesis
      should take into account TPC heterogeneity due to intratumour clonal evolution.

PMID- 21731719
TI  - Por secretion system-dependent secretion and glycosylation of Porphyromonas
      gingivalis hemin-binding protein 35.
AB  - The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major
      pathogen in severe forms of periodontal disease and refractory periapical
      perodontitis. We have recently found that P. gingivalis has a novel secretion
      system named the Por secretion system (PorSS), which is responsible for secretion
      of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain.
      These proteinases contain conserved C-terminal domains (CTDs) in their C-termini.
      Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of
      P. gingivalis and contributes to its haem utilization, also contains a CTD,
      suggesting that HBP35 is translocated to the cell surface via the PorSS. In this
      study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in
      the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed
      that HBP35 is translocated to the cell surface via the PorSS and is glycosylated
      with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent
      protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to
      be required for cell surface translocation and glycosylation. The GFP-CTD fusion
      study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and
      RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD
      region peptides were not found in samples of glycosylated HBP35 protein by
      peptide map fingerprinting analysis, and antibodies against CTD-regions peptides
      did not react with glycosylated HBP35 protein. These results suggest both that
      the CTD region functions as a recognition signal for the PorSS and that
      glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits
      were used for making antisera against bacterial proteins in this study.

PMID- 21731720
TI  - N. elongata produces type IV pili that mediate interspecies gene transfer with N.
      gonorrhoeae.
AB  - The genus Neisseria contains at least eight commensal and two pathogenic species.
      According to the Neisseria phylogenetic tree, commensals are basal to the
      pathogens. N. elongata, which is at the opposite end of the tree from N.
      gonorrhoeae, has been observed to be fimbriated, and these fimbriae are
      correlated with genetic competence in this organism. We tested the hypothesis
      that the fimbriae of N. elongata are Type IV pili (Tfp), and that Tfp functions
      in genetic competence. We provide evidence that the N. elongata fimbriae are
      indeed Tfp. Tfp, as well as the DNA Uptake Sequence (DUS), greatly enhance N.
      elongata DNA transformation. Tfp allows N. elongata to make intimate contact with
      N. gonorrhoeae and to mediate the transfer of antibiotic resistance markers
      between these two species. We conclude that Tfp functional for genetic competence
      is a trait of a commensal member of the Neisseria genus. Our findings provide a
      mechanism for the horizontal gene transfer that has been observed among Neisseria
      species.

PMID- 21731721
TI  - Sequence imputation of HPV16 genomes for genetic association studies.
AB  - BACKGROUND: Human Papillomavirus type 16 (HPV16) causes over half of all cervical
      cancer and some HPV16 variants are more oncogenic than others. The genetic basis
      for the extraordinary oncogenic properties of HPV16 compared to other HPVs is
      unknown. In addition, we neither know which nucleotides vary across and within
      HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs)
      determine oncogenicity. METHODS: A reference set of 62 HPV16 complete genome
      sequences was established and used to examine patterns of evolutionary
      relatedness amongst variants using a pairwise identity heatmap and HPV16
      phylogeny. A BLAST-based algorithm was developed to impute complete genome data
      from partial sequence information using the reference database. To interrogate
      the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP
      were calculated in a case-control viral genome-wide association study (VWAS)
      using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16
      infections from Guanacaste, Costa Rica. RESULTS: HPV16 variants display
      evolutionarily stable lineages that contain conserved diagnostic SNPs. The
      imputation algorithm indicated that an average of 97.5+/-1.03% of SNPs could be
      accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with
      variant lineages and elevated odds ratios; however, individual causal SNPs could
      not be distinguished with certainty due to the nature of HPV evolution.
      CONCLUSIONS: Conserved and lineage-specific SNPs can be imputed with a high
      degree of accuracy from limited viral polymorphic data due to the lack of
      recombination and the stochastic mechanism of variation accumulation in the HPV
      genome. However, to determine the role of novel variants or non-lineage-specific
      SNPs by VWAS will require direct sequence analysis. The investigation of patterns
      of genetic variation and the identification of diagnostic SNPs for lineages of
      HPV16 variants provides a valuable resource for future studies of HPV16
      pathogenicity.

PMID- 21731722
TI  - Soil microbial responses to elevated CO2 and O3 in a nitrogen-aggrading
      agroecosystem.
AB  - Climate change factors such as elevated atmospheric carbon dioxide (CO2) and
      ozone (O3) can exert significant impacts on soil microbes and the ecosystem level
      processes they mediate. However, the underlying mechanisms by which soil microbes
      respond to these environmental changes remain poorly understood. The prevailing
      hypothesis, which states that CO2- or O3-induced changes in carbon (C)
      availability dominate microbial responses, is primarily based on results from
      nitrogen (N)-limiting forests and grasslands. It remains largely unexplored how
      soil microbes respond to elevated CO2 and O3 in N-rich or N-aggrading systems,
      which severely hinders our ability to predict the long-term soil C dynamics in
      agroecosystems. Using a long-term field study conducted in a no-till wheat
      soybean rotation system with open-top chambers, we showed that elevated CO2 but
      not O3 had a potent influence on soil microbes. Elevated CO2(1.5*ambient)
      significantly increased, while O3 (1.4*ambient) reduced, aboveground (and
      presumably belowground) plant residue C and N inputs to soil. However, only
      elevated CO2 significantly affected soil microbial biomass, activities (namely
      heterotrophic respiration) and community composition. The enhancement of
      microbial biomass and activities by elevated CO2 largely occurred in the third
      and fourth years of the experiment and coincided with increased soil N
      availability, likely due to CO2-stimulation of symbiotic N2 fixation in soybean.
      Fungal biomass and the fungi?bacteria ratio decreased under both ambient and
      elevated CO2 by the third year and also coincided with increased soil N
      availability; but they were significantly higher under elevated than ambient CO2.
      These results suggest that more attention should be directed towards assessing
      the impact of N availability on microbial activities and decomposition in
      projections of soil organic C balance in N-rich systems under future CO2
      scenarios.

PMID- 21731723
TI  - Interleukin-8 is activated in patients with chronic liver diseases and associated
      with hepatic macrophage accumulation in human liver fibrosis.
AB  - BACKGROUND: Interleukin-8 (IL-8, CXCL8) is a potent chemoattractant for
      neutrophils and contributes to acute liver inflammation. Much less is known about
      IL-8 in chronic liver diseases (CLD), but elevated levels were reported from
      alcoholic and hepatitis C-related CLD. We investigated the regulation of IL-8,
      its receptors CXCR1 and CXCR2 and possible IL-8 responding cells in CLD patients.
      METHODOLOGY: Serum IL-8 levels were measured in CLD patients (n = 200) and
      healthy controls (n = 141). Intrahepatic IL-8, CXCR1 and CXCR2 gene expression
      was quantified from liver samples (n = 41), alongside immunohistochemical
      neutrophil (MPO) and macrophage (CD68) stainings. CXCR1 and CXCR2 expression was
      analyzed on purified monocytes from patients (n = 111) and controls (n = 31). In
      vitro analyses explored IL-8 secretion by different leukocyte subsets. PRINCIPAL
      FINDINGS: IL-8 serum levels were significantly increased in CLD patients,
      especially in end-stage cirrhosis. Interestingly, patients with cholestatic
      diseases exhibited highest IL-8 serum concentrations. IL-8 correlated with liver
      function, inflammatory cytokines and non-invasive fibrosis markers.
      Intrahepatically, IL-8 and CXCR1 expression were strongly up-regulated. However,
      intrahepatic IL-8 could only be associated to neutrophil infiltration in patients
      with primary biliary cirrhosis (PBC). In non-cholestatic cirrhosis, increased IL
      8 and CXCR1 levels were associated with hepatic macrophage accumulation. In line,
      CXCR1, but not CXCR2 or CXCR3, expression was increased on circulating monocytes
      from cirrhotic patients. Moreover, monocyte-derived macrophages from CLD
      patients, especially the non-classical CD16+ subtype, displayed enhanced IL-8
      secretion in vitro. CONCLUSIONS: IL-8 is strongly activated in CLD, thus likely
      contributing to hepatic inflammation. Our study suggests a novel role of IL-8 for
      recruitment and activation of hepatic macrophages via CXCR1 in human liver
      cirrhosis.

PMID- 21731724
TI  - Friends and foes from an ant brain's point of view--neuronal correlates of colony
      odors in a social insect.
AB  - BACKGROUND: Successful cooperation depends on reliable identification of friends
      and foes. Social insects discriminate colony members (nestmates/friends) from
      foreign workers (non-nestmates/foes) by colony-specific, multi-component colony
      odors. Traditionally, complex processing in the brain has been regarded as
      crucial for colony recognition. Odor information is represented as spatial
      patterns of activity and processed in the primary olfactory neuropile, the
      antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory
      bulb. Correlative evidence indicates that the spatial activity patterns reflect
      odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a
      sensory filter in the peripheral nervous system was suggested, causing specific
      anosmia to nestmate colony odors. Here, we investigate neuronal correlates of
      colony odors in the brain of a social insect to directly test whether they are
      anosmic to nestmate colony odors and whether spatial activity patterns in the AL
      can predict how odor qualities like "friend" and "foe" are attributed to colony
      odors. METHODOLOGY/PRINCIPAL FINDINGS: Using ant dummies that mimic natural
      conditions, we presented colony odors and investigated their neuronal
      representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony
      odors elicited neuronal activity: In the periphery, we recorded sensory responses
      of olfactory receptor neurons (electroantennography), and in the brain, we
      measured colony odor specific spatial activity patterns in the AL (calcium
      imaging). Surprisingly, upon repeated stimulation with the same colony odor,
      spatial activity patterns were variable, and as variable as activity patterns
      elicited by different colony odors. CONCLUSIONS: Ants are not anosmic to nestmate
      colony odors. However, spatial activity patterns in the AL alone do not provide
      sufficient information for colony odor discrimination and this finding challenges
      the current notion of how odor quality is coded. Our result illustrates the
      enormous challenge for the nervous system to classify multi-component odors and
      indicates that other neuronal parameters, e.g., precise timing of neuronal
      activity, are likely necessary for attribution of odor quality to multi-component
      odors.

PMID- 21731725
TI  - Mitochondrial DNA signature for range-wide populations of Bicyclus anynana
      suggests a rapid expansion from recent refugia.
AB  - This study investigates the genetic diversity, population structure and
      demographic history of the afrotropical butterfly Bicyclus anynana using
      mitochondrial DNA (mtDNA). Samples from six wild populations covering most of the
      species range from Uganda to South Africa were compared for the cytochrome c
      oxidase subunit gene (COI). Molecular diversity indices show overall high mtDNA
      diversity for the populations, but low nucleotide divergence between haplotypes.
      Our results indicate relatively little geographic population structure among the
      southern populations, especially given the extensive distributional range and an
      expectation of limited gene flow between populations. We implemented neutrality
      tests to assess signatures of recent historical demographic events. Tajima's D
      test and Fu's F(S) test both suggested recent population growth for the
      populations. The results were only significant for the southernmost populations
      when applying Tajima's D, but Fu's F(S) indicated significant deviations from
      neutrality for all populations except the one closest to the equator. Based on
      our own findings and those from pollen and vegetation studies, we hypothesize
      that the species range of B. anynana was reduced to equatorial refugia during the
      last glacial period, and that the species expanded southwards during the past
      10.000 years. These results provide crucial background information for studies of
      phenotypic and molecular adaptation in wild populations of B. anynana.

PMID- 21731726
TI  - T regulatory cells are markers of disease activity in multiple sclerosis
      patients.
AB  - FoxP3+ Treg cells are believed to play a role in the occurrence of autoimmunity
      and in the determination of clinical recurrences. Contradictory reports are,
      however, available describing frequency and function of Treg cells during
      autoimmune diseases. We examined, by both polychromatic flow cytometry, and real
      time RT-PCR, several Treg markers in peripheral blood mononuclear cells from
      patients with multiple sclerosis (MS), an autoimmune disease affecting the
      central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3,
      CTLA4, and GITR expression, were significantly decreased in stable MS patients as
      compared to healthy donors, but, surprisingly, restored to normal levels during
      an acute clinical attack. We conclude that Treg cells are not involved in causing
      clinical relapses, but rather react to inflammation in the attempt to restore
      homeostasis.

PMID- 21731727
TI  - GNE is involved in the early development of skeletal and cardiac muscle.
AB  - UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamime kinase (GNE) is a
      bifunctional enzyme which catalyzes the two key sequential steps in the
      biosynthetic pathway of sialic acid, the most abundant terminal monosaccharide on
      glycoconjugates of eukaryotic cells. GNE knock out (GNE KO) mice are
      embryonically lethal at day E8.5. Although the role of GNE in the sialic pathway
      has been well established as well as the importance of sialylation in many
      diverse biological pathways, less is known about the involvement of GNE in muscle
      development. To address this issue we have studied the role of GNE during in
      vitro embryogenesis by comparing the developmental profile in culture of
      embryonic stem cells (ES) from wild type and from GNE KO E3.5 mice embryos,
      during 45 days. Neuronal cells appeared rarely in GNE KO ES cultures and did not
      reach an advanced differentiated stage. Although primary cardiac cells appeared
      at the same time in both normal and GNE KO ES cultures, GNE KO cardiac cells
      degraded very soon and their beating capacity decayed rapidly. Furthermore very
      rare skeletal muscle committed cells were detected in the GNE KO ES cultures at
      any stage of differentiation, as assessed by analysis of the expression of either
      Pax7, MyoD and MyHC markers. Beyond the supporting evidence that GNE plays an
      important role in neuronal cell and brain development, these results show that
      GNE is strongly involved in cardiac tissue and skeletal muscle early survival and
      organization. These findings could open new avenues in the understanding of
      muscle function mechanisms in health and in disease.

PMID- 21731728
TI  - Insights into the regulatory characteristics of the mycobacterial
      dephosphocoenzyme A kinase: implications for the universal CoA biosynthesis
      pathway.
AB  - Being vastly different from the human counterpart, we suggest that the last
      enzyme of the Mycobacterium tuberculosis Coenzyme A biosynthetic pathway,
      dephosphocoenzyme A kinase (CoaE) could be a good anti-tubercular target. Here we
      describe detailed investigations into the regulatory features of the enzyme,
      affected via two mechanisms. Enzymatic activity is regulated by CTP which
      strongly binds the enzyme at a site overlapping that of the leading substrate,
      dephosphocoenzyme A (DCoA), thereby obscuring the binding site and limiting
      catalysis. The organism has evolved a second layer of regulation by employing a
      dynamic equilibrium between the trimeric and monomeric forms of CoaE as a means
      of regulating the effective concentration of active enzyme. We show that the
      monomer is the active form of the enzyme and the interplay between the regulator,
      CTP and the substrate, DCoA, affects enzymatic activity. Detailed kinetic data
      have been corroborated by size exclusion chromatography, dynamic light
      scattering, glutaraldehyde crosslinking, limited proteolysis and fluorescence
      investigations on the enzyme all of which corroborate the effects of the ligands
      on the enzyme oligomeric status and activity. Cysteine mutagenesis and the
      effects of reducing agents on mycobacterial CoaE oligomerization further validate
      that the latter is not cysteine-mediated or reduction-sensitive. These studies
      thus shed light on the novel regulatory features employed to regulate metabolite
      flow through the last step of a critical biosynthetic pathway by keeping the
      latter catalytically dormant till the need arises, the transition to the active
      form affected by a delicate crosstalk between an essential cellular metabolite
      (CTP) and the precursor to the pathway end-product (DCoA).

PMID- 21731729
TI  - Radioactive phosphorylation of alcohols to monitor biocatalytic Diels-Alder
      reactions.
AB  - Nature has efficiently adopted phosphorylation for numerous biological key
      processes, spanning from cell signaling to energy storage and transmission. For
      the bioorganic chemist the number of possible ways to attach a single phosphate
      for radioactive labeling is surprisingly small. Here we describe a very simple
      and fast one-pot synthesis to phosphorylate an alcohol with phosphoric acid using
      trichloroacetonitrile as activating agent. Using this procedure, we efficiently
      attached the radioactive phosphorus isotope (32)P to an anthracene diene, which
      is a substrate for the Diels-Alderase ribozyme-an RNA sequence that catalyzes the
      eponymous reaction. We used the (32)P-substrate for the measurement of RNA
      catalyzed reaction kinetics of several dye-labeled ribozyme variants for which
      precise optical activity determination (UV/vis, fluorescence) failed due to
      interference of the attached dyes. The reaction kinetics were analyzed by thin
      layer chromatographic separation of the (32)P-labeled reaction components and
      densitometric analysis of the substrate and product radioactivities, thereby
      allowing iterative optimization of the dye positions for future single-molecule
      studies. The phosphorylation strategy with trichloroacetonitrile may be
      applicable for labeling numerous other compounds that contain alcoholic hydroxyl
      groups.

PMID- 21731730
TI  - Qualitative real-time schlieren and shadowgraph imaging of human exhaled
      airflows: an aid to aerosol infection control.
AB  - Using a newly constructed airflow imaging system, airflow patterns were
      visualized that were associated with common, everyday respiratory activities
      (e.g. breathing, talking, laughing, whistling). The effectiveness of various
      interventions (e.g. putting hands and tissues across the mouth and nose) to
      reduce the potential transmission of airborne infection, whilst coughing and
      sneezing, were also investigated. From the digital video footage recorded, it was
      seen that both coughing and sneezing are relatively poorly contained by commonly
      used configurations of single-handed shielding maneuvers. Only some but not all
      of the forward momentum of the cough and sneeze puffs are curtailed with various
      hand techniques, and the remaining momentum is disseminated in a large puff in
      the immediate vicinity of the cougher, which may still act as a nearby source of
      infection. The use of a tissue (in this case, 4-ply, opened and ready in the
      hand) proved to be surprisingly effective, though the effectiveness of this
      depends on the tissue remaining intact and not ripping apart. Interestingly, the
      use of a novel 'coughcatcher' device appears to be relatively effective in
      containing coughs and sneezes. One aspect that became evident during the
      experimental procedures was that the effectiveness of all of these barrier
      interventions is very much dependent on the speed with which the user can put
      them into position to cover the mouth and nose effectively.From these qualitative
      schlieren and shadowgraph imaging experiments, it is clear that making some
      effort to contain one's cough or sneeze puffs is worthwhile. Obviously, there
      will be a large amount of variation between individuals in the exact hand or
      tissue (the most common methods) configuration used for this and other practical
      factors may hinder such maneuvers in daily life, for example, when carrying
      shopping bags or managing young children.

PMID- 21731731
TI  - Genome assembly has a major impact on gene content: a comparison of annotation in
      two Bos taurus assemblies.
AB  - Gene and SNP annotation are among the first and most important steps in analyzing
      a genome. As the number of sequenced genomes continues to grow, a key question
      is: how does the quality of the assembled sequence affect the annotations? We
      compared the gene and SNP annotations for two different Bos taurus genome
      assemblies built from the same data but with significant improvements in the
      later assembly. The same annotation software was used for annotating both
      sequences. While some annotation differences are expected even between high
      quality assemblies such as these, we found that a staggering 40% of the genes
      (>9,500) varied significantly between assemblies, due in part to the availability
      of new gene evidence but primarily to genome mis-assembly events and local
      sequence variations. For instance, although the later assembly is generally
      superior, 660 protein coding genes in the earlier assembly are entirely missing
      from the later genome's annotation, and approximately 3,600 (15%) of the genes
      have complex structural differences between the two assemblies. In addition, 12
      20% of the predicted proteins in both assemblies have relatively large sequence
      differences when compared to their RefSeq models, and 6-15% of bovine dbSNP
      records are unrecoverable in the two assemblies. Our findings highlight the
      consequences of genome assembly quality on gene and SNP annotation and argue for
      continued improvements in any draft genome sequence. We also found that tracking
      a gene between different assemblies of the same genome is surprisingly difficult,
      due to the numerous changes, both small and large, that occur in some genes. As a
      side benefit, our analyses helped us identify many specific loci for improvement
      in the Bos taurus genome assembly.

PMID- 21731732
TI  - Reduced bone mass and muscle strength in male 5alpha-reductase type 1 inactivated
      mice.
AB  - Androgens are important regulators of bone mass but the relative importance of
      testosterone (T) versus dihydrotestosterone (DHT) for the activation of the
      androgen receptor (AR) in bone is unknown. 5alpha-reductase is responsible for
      the irreversible conversion of T to the more potent AR activator DHT. There are
      two well established isoenzymes of 5alpha-reductase (type 1 and type 2), encoded
      by separate genes (Srd5a1 and Srd5a2). 5alpha-reductase type 2 is predominantly
      expressed in male reproductive tissues whereas 5alpha-reductase type 1 is highly
      expressed in liver and moderately expressed in several other tissues including
      bone. The aim of the present study was to investigate the role of 5alpha
      reductase type 1 for bone mass using Srd5a1-/- mice. Four-month-old male Srd5a1-/
      mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical
      bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared
      with wild type (WT) mice. The cortical bone dimensions were reduced in the male
      Srd5a1-/- mice as a result of a reduced cortical periosteal circumference
      compared with WT mice. T treatment increased the cortical periosteal
      circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized
      Srd5a1-/- mice. Male Srd5a1-/- mice demonstrated a reduced forelimb muscle grip
      strength compared with WT mice (p<0.05). Female Srd5a1-/- mice had slightly
      increased cortical bone mass associated with elevated circulating levels of
      androgens. In conclusion, 5alpha-reductase type 1 inactivated male mice have
      reduced bone mass and forelimb muscle grip strength and we propose that these
      effects are due to lack of 5alpha-reductase type 1 expression in bone and muscle.
      In contrast, the increased cortical bone mass in female Srd5a1-/- mice, is an
      indirect effect mediated by elevated circulating androgen levels.

PMID- 21731733
TI  - Academic impact of a public electronic health database: bibliometric analysis of
      studies using the general practice research database.
AB  - BACKGROUND: Studies that use electronic health databases as research material are
      getting popular but the influence of a single electronic health database had not
      been well investigated yet. The United Kingdom's General Practice Research
      Database (GPRD) is one of the few electronic health databases publicly available
      to academic researchers. This study analyzed studies that used GPRD to
      demonstrate the scientific production and academic impact by a single public
      health database. METHODOLOGY AND FINDINGS: A total of 749 studies published
      between 1995 and 2009 with 'General Practice Research Database' as their topics,
      defined as GPRD studies, were extracted from Web of Science. By the end of 2009,
      the GPRD had attracted 1251 authors from 22 countries and been used extensively
      in 749 studies published in 193 journals across 58 study fields. Each GPRD study
      was cited 2.7 times by successive studies. Moreover, the total number of GPRD
      studies increased rapidly, and it is expected to reach 1500 by 2015, twice the
      number accumulated till the end of 2009. Since 17 of the most prolific authors
      (1.4% of all authors) contributed nearly half (47.9%) of GPRD studies, success in
      conducting GPRD studies may accumulate. The GPRD was used mainly in, but not
      limited to, the three study fields of "Pharmacology and Pharmacy", "General and
      Internal Medicine", and "Public, Environmental and Occupational Health". The UK
      and United States were the two most active regions of GPRD studies. One-third of
      GRPD studies were internationally co-authored. CONCLUSIONS: A public electronic
      health database such as the GPRD will promote scientific production in many ways.
      Data owners of electronic health databases at a national level should consider
      how to reduce access barriers and to make data more available for research.

PMID- 21731734
TI  - Dynamic changes of the phosphoproteome in postmortem mouse brains.
AB  - Protein phosphorylation is deeply involved in the pathological mechanism of
      various neurodegenerative disorders. However, in human pathological samples,
      phosphorylation can be modified during preservation by postmortem factors such as
      time and temperature. Postmortem changes may also differ among proteins.
      Unfortunately, there is no comprehensive database that could support the analysis
      of protein phosphorylation in human brain samples from the standpoint of
      postmortem changes. As a first step toward addressing the issue, we performed
      phosphoproteome analysis with brain tissue dissected from mouse bodies preserved
      under different conditions. Quantitative whole proteome mass analysis showed
      surprisingly diverse postmortem changes in phosphoproteins that were dependent on
      temperature, time and protein species. Twelve hrs postmortem was a critical time
      point for preservation at room temperature. At 4 degrees C, after the body was
      cooled down, most phosphoproteins were stable for 72 hrs. At either temperature,
      increase greater than 2-fold was exceptional during this interval. We found
      several standard proteins by which we can calculate the postmortem time at room
      temperature. The information obtained in this study will be indispensable for
      evaluating experimental data with human as well as mouse brain samples.

PMID- 21731735
TI  - Speed controls the amplitude and timing of the hippocampal gamma rhythm.
AB  - Cortical and hippocampal gamma oscillations have been implicated in many
      behavioral tasks. The hippocampus is required for spatial navigation where
      animals run at varying speeds. Hence we tested the hypothesis that the gamma
      rhythm could encode the running speed of mice. We found that the amplitude of
      slow (20-45 Hz) and fast (45-120 Hz) gamma rhythms in the hippocampal local field
      potential (LFP) increased with running speed. The speed-dependence of gamma
      amplitude was restricted to a narrow range of theta phases where gamma amplitude
      was maximal, called the preferred theta phase of gamma. The preferred phase of
      slow gamma precessed to lower values with increasing running speed. While maximal
      fast and slow gamma occurred at coincident phases of theta at low speeds, they
      became progressively more theta-phase separated with increasing speed. These
      results demonstrate a novel influence of speed on the amplitude and timing of the
      hippocampal gamma rhythm which could contribute to learning of temporal sequences
      and navigation.

PMID- 21731736
TI  - Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced
      apoptosis and DNA damage by nucleotide excision repair mechanism.
AB  - Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor
      for melanoma and non-melanoma skin cancers. This observation has been linked to
      the accumulation of UVB radiation-induced DNA lesions in cells, and that finally
      lead to the development of skin cancers. Earlier, we have shown that topical
      treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum
      marianum), inhibits photocarcinogenesis in mice; however it is less understood
      whether chemopreventive effect of silymarin is mediated through the repair of DNA
      lesions in skin cells and that protect the cells from apoptosis. Here, we show
      that treatment of normal human epidermal keratinocytes (NHEK) with silymarin
      blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of
      UVB radiation-induced DNA damage as demonstrated by reduced amounts of
      cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that
      ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation
      induced DNA damage by silymarin appears to be related with induction of
      nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis
      was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and
      dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER
      proficient fibroblasts from a healthy individual but did not repair UV-induced
      CPD-positive cells in NER-deficient fibroblasts from patients suffering from
      xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical
      analysis revealed that silymarin did not reduce the number of UVB-induced
      sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number
      of sunburn cells in their wild-type counterparts. Together, these results suggest
      that silymarin exert the capacity to reduce UV radiation-induced DNA damage and,
      thus, prevent the harmful effects of UV radiation on the genomic stability of
      epidermal cells.

PMID- 21731737
TI  - Blockade of VEGFR1 and 2 suppresses pathological angiogenesis and vascular
      leakage in the eye.
AB  - OBJECTIVE: VEGFR1 and 2 signaling have both been increasingly shown to mediate
      complications of ischemic retinopathies, including retinopathy of prematurity
      (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR).
      This study evaluates the effects of blocking VEGFR1 and 2 on pathological
      angiogenesis and vascular leakage in ischemic retinopathy in a model of ROP and
      in choroidal neovascularization (CNV) in a model of AMD. MATERIALS AND METHODS:
      Neutralizing antibodies specific for mouse VEGFR1 (MF1) and VEGFR2 (DC101) were
      administrated systemically. CNV was induced by laser photocoagulation and
      assessed 14d after laser treatment. Retinal NV was generated in oxygen-induced
      ischemic retinopathy (OIR) and assessed at p17. NV quantification was determined
      by measuring NV tufts and vascular leakage was quantified by measuring [(3)H]
      mannitol leakage from blood vessels into the retina. Gene expression was measured
      by real-time quantitative (Q)PCR. RESULTS: VEGFR1 and VEGFR2 expressions were up
      regulated during CNV pathogenesis. Both MF1 and DC101 significantly suppressed
      CNV at 50 mg/kg: DC101 suppressed CNV by 73+/-5% (p<0.0001) and MF1 by 64+/-6% (p
      = 0.0002) in a dosage-dependent manner. The combination of MF1 and DC101 enhanced
      the inhibitory efficacy and resulted in an accumulation of retinal microglia at
      the CNV lesion. Similarly, both MF1 and DC101 significantly suppressed retinal NV
      in OIR at 50 mg/kg: DC101 suppressed retinal NV by 54+/-8% (p = 0.013) and MF1 by
      50+/-7% (p<0.0002). MF1 was even more effective at inhibiting ischemia-induced
      BRB breakdown than DC101: the retina/lung leakage ratio for MF1 was reduced by
      73+/-24%, p = 0.001 and for DC101 by 12+/-4%, p = 0.003. The retina/renal leakage
      ratio for MF1 was reduced by 52+/-28%, p = 0.009 and for DC101 by 13+/-4%, p =
      0.001. CONCLUSION: Our study provides further evidence that both VEGFR1 and 2
      mediate pathological angiogenesis and vascular leakage in these models of ocular
      disease and suggests that antagonist antibodies to these receptor tyrosine
      kinases (RTKs) are potential therapeutic agents.

PMID- 21731738
TI  - Molecular and cellular characterization of an AT-hook protein from Leishmania.
AB  - AT-rich DNA, and the proteins that bind it (AT-hook proteins), modulate
      chromosome structure and function in most eukaryotes. Unlike other
      trypanosomatids, the genome of Leishmania species is unusually GC-rich, and the
      regulation of Leishmania chromosome structure, replication, partitioning is not
      fully understood. Because AT-hook proteins modulate these functions in other
      eukaryotes, we examined whether AT-hook proteins are encoded in the Leishmania
      genome, to test their potential functions. Several Leishmania ORFs predicted to
      be AT-hook proteins were identified using in silico approaches based on sequences
      shared between eukaryotic AT-hook proteins. We have used biochemical, molecular
      and cellular techniques to characterize the L. amazonensis ortholog of the L.
      major protein LmjF06.0720, a potential AT-hook protein that is highly conserved
      in Leishmania species. Using a novel fusion between the AT-hook domain encoded by
      LmjF06.0720 and a herpesviral protein, we have demonstrated that LmjF06.0720
      functions as an AT-hook protein in mammalian cells. Further, as observed for
      mammalian and viral AT-hook proteins, the AT-hook domains of LmjF06.0720 bind
      specific regions of condensed mammalian metaphase chromosomes, and support the
      licensed replication of DNA in mammalian cells. LmjF06.0720 is nuclear in
      Leishmania, and this localization is disrupted upon exposure to drugs that
      displace AT-hook proteins from AT-rich DNA. Coincidentally, these drugs
      dramatically alter the cellular physiology of Leishmania promastigotes. Finally,
      we have devised a novel peptido-mimetic agent derived from the sequence of
      LmjF06.0720 that blocks the proliferation of Leishmania promastigotes, and lowers
      amastigote parasitic burden in infected macrophages. Our results indicate that AT
      hook proteins are critical for the normal biology of Leishmania. In addition, we
      have described a simple technique to examine the function of Leishmania chromatin
      binding proteins in a eukaryotic context amenable to studying chromosome
      structure and function. Lastly, we demonstrate the therapeutic potential of
      compounds directed against AT-hook proteins in Leishmania.

PMID- 21731739
TI  - Intrinsic order and disorder in the bcl-2 member harakiri: insights into its
      proapoptotic activity.
AB  - Harakiri is a BH3-only member of the Bcl-2 family that localizes in membranes and
      induces cell death by binding to prosurvival Bcl-x(L) and Bcl-2. The cytosolic
      domain of Harakiri is largely disorder with residual alpha-helical conformation
      according to previous structural studies. As these helical structures could play
      an important role in Harakiri's function, we have used NMR and circular dichroism
      to fully characterize them at the residue-atomic level. In addition, we report
      structural studies on a peptide fragment spanning Harakiri's C-terminal
      hydrophobic sequence, which potentially operates as a transmembrane domain. We
      initially checked by enzyme immunoassays and NMR that peptides encompassing
      different lengths of the cytosolic domain are functional as they bind Bcl-x(L)
      and Bcl-2. The structural data in water indicate that the alpha-helical
      conformation is restricted to a 25-residue segment comprising the BH3 domain.
      However, structure calculation was precluded because of insufficient NMR
      restraints. To bypass this problem we used alcohol-water mixture to increase
      structure population and confirmed by NMR that the conformation in both milieus
      is equivalent. The resulting three-dimensional structure closely resembles that
      of peptides encompassing the BH3 domain of BH3-only members in complex with their
      prosurvival partners, suggesting that preformed structural elements in the
      disordered protein are central to binding. In contrast, the transmembrane domain
      forms in micelles a monomeric alpha-helix with a population close to 100%. Its
      three-dimensional structure here reported reveals features that explain its
      function as membrane anchor. Altogether these results are used to propose a
      tentative structural model of how Harakiri works.

PMID- 21731740
TI  - Tumor initiating cells in esophageal squamous cell carcinomas express high levels
      of CD44.
AB  - BACKGROUND: Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of
      esophageal cancer causing significant morbility and mortality in Asia. Mechanism
      of initiation and progression of this disease is unclear. Tumor initiating cells
      (TICs) are the subpopulation of cells which have the ability to self-renew, as
      well as, to drive initiation and progression of cancer. Increasing evidence has
      shown that TICs exist in a variety of tumors. However, the identification and
      characterization of TICs in esophageal carcinoma has remained elusive.
      METHODOLOGY/PRINCIPAL FINDINGS: to identify TICs in ESCC, ESCC cell lines
      including two primary cells were used for screening suitable surface marker. Then
      colony formation assay, drug resistant assay and tumorigenicity assay in immune
      deficient mice were used to characterize TICs in ESCC. We found that just the
      CD44 expression correlated with tumorigenicity in ESCC cell lines. And then
      induced differentiation of ESCC cells by all-trans retinoic acid treatment led to
      decreased expression of CD44. The FACS isolated cell subpopulations with high
      CD44 expression showed increased colony formation and drug resistance in vitro,
      as well as significantly enhanced tumorigenicity in NOD/SICD mice, as compared to
      the low expressing CD44 ESCC cells. CONCLUSIONS/SIGNIFICANCE: our study has
      discovered a novel TIC surface marker, CD44, which can be utilized to enrich
      efficiently the TICs in ESCC. These findings will be useful for further studies
      of these cells and exploring therapeutic approaches.

PMID- 21731741
TI  - Cell-free antigens from Paracoccidioides brasiliensis drive IL-4 production and
      increase the severity of paracoccidioidomycosis.
AB  - The thermally dimorphic fungus Paracoccidioides brasiliensis (Pb) is the
      causative agent of paracoccidioidomycosis (PCM), one of the most frequent
      systemic mycosis that affects the rural population in Latin America. PCM is
      characterized by a chronic inflammatory granulomatous reaction, which is
      consequence of a Th1-mediated adaptive immune response. In the present study we
      investigated the mechanisms involved in the immunoregulation triggered after a
      prior contact with cell-free antigens (CFA) during a murine model of PCM. The
      results showed that the inoculation of CFA prior to the infection resulted in
      disorganized granulomatous lesions and increased fungal replication in the lungs,
      liver and spleen, that paralleled with the higher levels of IL-4 when compared
      with the control group. The role of IL-4 in facilitating the fungal growth was
      demonstrated in IL-4-deficient- and neutralizing anti-IL-4 mAb-treated mice. The
      injection of CFA did not affect the fungal growth in these mice, which, in fact,
      exhibited a significant diminished amount of fungus in the tissues and smaller
      granulomas. Considering that in vivo anti-IL-4-application started one week after
      the CFA-inoculum, it implicates that IL-4-CFA-induced is responsible by the
      mediation of the observed unresponsiveness. Further, the characterization of CFA
      indicated that a proteic fraction is required for triggering the
      immunosuppressive mechanisms, while glycosylation or glycosphingolipids moieties
      are not. Taken together, our data suggest that the prior contact with soluble Pb
      antigens leads to severe PCM in an IL-4 dependent manner.

PMID- 21731742
TI  - DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses
      sister chromatid exchange.
AB  - Hyperphosphorylation of RPA2 at serine 4 and serine 8 (S4, S8) has been used as a
      marker for activation of the DNA damage response. What types of DNA lesions cause
      RPA2 hyperphosphorylation, which kinase(s) are responsible for them, and what is
      the biological outcome of these phosphorylations, however, have not been fully
      investigated. In this study we demonstrate that RPA2 hyperphosphorylation occurs
      primarily in response to genotoxic stresses that cause high levels of DNA double
      strand breaks (DSBs) and that the DNA-dependent protein kinase complex (DNA-PK)
      is responsible for the modifications in vivo. Alteration of S4, S8 of RPA2 to
      alanines, which prevent phosphorylations at these sites, caused increased mitotic
      entry with concomitant increases in RAD51 foci and homologous recombination.
      Taken together, our results demonstrate that RPA2 hyperphosphorylation by DNA-PK
      in response to DSBs blocks unscheduled homologous recombination and delays
      mitotic entry. This pathway thus permits cells to repair DNA damage properly and
      increase cell viability.

PMID- 21731743
TI  - Behavioral and endocrine consequences of simultaneous exposure to two different
      stressors in rats: interaction or independence?
AB  - Although behavioral and endocrine consequences of acute exposure to stressors
      have been extensively studied, little is known about how simultaneous exposure to
      two different stressors interacts to induce short- and long-term effects. In the
      present experiment we studied this interaction in adult male rats exposed to cat
      fur odor (impregnated cloth) or immobilization on boards either separately or
      simultaneously. We reasoned that exposure to the odor of a potential predator
      while immobilized, may potentiate its negative consequences as compared to
      exposure to only one of the stressors. Exposure to cat odor elicited the expected
      reduction of activity and avoidance of the area where the impregnated cloth was
      located. The endocrine response (plasma levels of ACTH and corticosterone, as a
      measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater
      after immobilization than after cat fur odor and no additive effects were found
      by simultaneous exposure to both stressors. Cat odor, but not immobilization,
      increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days
      after the stressors, with no evidence of enhanced HPA activation. In addition,
      cat odor exposure resulted in long-lasting (8 days later) fear conditioning to
      the box containing a clean cloth, which was reflected by hypoactivity, avoidance
      of the cloth area and enhanced HPA activation. All these effects were similarly
      observed in rats exposed simultaneously to cat odor and immobilization. In rats
      only exposed to immobilization, only some weak behavioral signs of fear
      conditioning were found, but HPA activation in response to the context paired to
      immobilization was enhanced to the same extent as in cat odor-exposed animals,
      supporting a certain degree of endocrine conditioning. The present results did
      not reveal important behavioral interactions between the two stressors when
      animals experienced both simultaneously, whereas some interactions were found
      regarding HPA activation. Theoretical implications are discussed.

PMID- 21731744
TI  - Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild
      type EGFR-expressing cells.
AB  - BACKGROUND: The sensitivity of non-small cell lung cancer (NSCLC) patients to
      EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating
      EGFR mutations. Although not as sensitive as patients harboring these mutations,
      some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs,
      suggesting that the existence of unexplored mechanisms renders most of wtEGFR
      expressing cancer cells insensitive. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI,
      gefitinib, is associated with elevated expression of breast cancer resistance
      protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In
      addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in
      both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with
      BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.
      CONCLUSIONS/SIGNIFICANCE: Thus, BCRP/ABCG2 expression may be a predictor for poor
      efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of
      gefitinib in patients with wtEGFR.

PMID- 21731745
TI  - Multiple insulin degrading enzyme variants alter in vitro reporter gene
      expression.
AB  - The insulin degrading enzyme (IDE) variant, v311 (rs6583817), is associated with
      increased post-mortem cerebellar IDE mRNA, decreased plasma beta-amyloid (Abeta),
      decreased risk for Alzheimer's disease (AD) and increased reporter gene
      expression, suggesting that it is a functional variant driving increased IDE
      expression. To identify other functional IDE variants, we have tested v685,
      rs11187061 (associated with decreased cerebellar IDE mRNA) and variants on H6,
      the haplotype tagged by v311 (v10; rs4646958, v315; rs7895832, v687; rs17107734
      and v154; rs4646957), for altered in vitro reporter gene expression. The reporter
      gene expression levels associated with the second most common haplotype (H2)
      successfully replicated the post-mortem findings in hepatocytoma (0.89 fold
      change, p = 0.04) but not neuroblastoma cells. Successful in vitro replication
      was achieved for H6 in neuroblastoma cells when the sequence was cloned 5' to the
      promoter (1.18 fold-change, p = 0.006) and 3' to the reporter gene (1.29 fold
      change, p = 0.003), an effect contributed to by four variants (v10, v315, v154
      and v311). Since IDE mediates Abeta degradation, variants that regulate IDE
      expression could represent good therapeutic targets for AD.

PMID- 21731746
TI  - Identification of a classical bipartite nuclear localization signal in the
      Drosophila TEA/ATTS protein scalloped.
AB  - Drosophila melanogaster wing development has been shown to rely on the activity
      of a complex of two proteins, Scalloped (Sd) and Vestigial (Vg). Within this
      complex, Sd is known to provide DNA binding though its TEA/ATTS domain, while Vg
      modulates this binding and provides transcriptional activation through N- and C
      terminal activation domains. There is also evidence that Sd is required for the
      nuclear translocation of Vg. Indeed, a candidate sequence which shows consensus
      to the bipartite family of nuclear localization signals (NLSs) has been
      identified within Sd previously, though it is not known if it is functional, or
      if additional unpredicted signals that mediate nuclear transport exist within the
      protein. By expressing various enhanced green fluorescent protein (eGFP) tagged
      constructs within Drosophila S2 cells, we demonstrate that this NLS is indeed
      functional and necessary for the proper nuclear localization of Sd. Additionally,
      the region containing the NLS is critical for the wildtype function of
      ectopically expressed Sd, in the context of wing development. Using site-directed
      mutagenesis, we have identified a group of five amino acids within this NLS which
      is critical for its function, as well as another group of two which is of lesser
      importance. Together with data that suggests that this sequence mediates
      interactions with Importin-alpha3, we conclude that the identified NLS is likely
      a classical bipartite signal. Further dissection of Sd has also revealed that a
      large portion of the C-terminal domain of the protein is required its proper
      nuclear localization. Finally, a Leptomycin B (LB) sensitive signal which appears
      to facilitate nuclear export is identified, raising the possibility that Sd also
      contains a nuclear export signal (NES).

PMID- 21731747
TI  - Birth preparedness and complication readiness among pregnant women in Southern
      Ethiopia.
AB  - BACKGROUND: Birth preparedness and complication preparedness (BPACR) is a key
      component of globally accepted safe motherhood programs, which helps ensure women
      to reach professional delivery care when labor begins and to reduce delays that
      occur when mothers in labor experience obstetric complications. OBJECTIVE: This
      study was conducted to assess practice and factors associated with BPACR among
      pregnant women in Aleta Wondo district in Sidama Zone, South Ethiopia. METHODS: A
      community based cross sectional study was conducted in 2007, on a sample of 812
      pregnant women. Data were collected using pre-tested and structured
      questionnaire. The collected data were analyzed by SPSS for windows version
      12.0.1. The women were asked whether they followed the desired five steps while
      pregnant: identified a trained birth attendant, identified a health facility,
      arranged for transport, identified blood donor and saved money for emergency.
      Taking at least two steps was considered being well-prepared. RESULTS: Among 743
      pregnant women only a quarter (20.5%) of pregnant women identified skilled
      provider. Only 8.1% identified health facility for delivery and/or for obstetric
      emergencies. Preparedness for transportation was found to be very low (7.7%).
      Considerable (34.5%) number of families saved money for incurred costs of
      delivery and emergency if needed. Only few (2.3%) identified potential blood
      donor in case of emergency. Majority (87.9%) of the respondents reported that
      they intended to deliver at home, and only 60(8%) planned to deliver at health
      facilities. Overall only 17% of pregnant women were well prepared. The adjusted
      multivariate model showed that significant predictors for being well-prepared
      were maternal availing of antenatal services (OR = 1.91 95% CI; 1.21-3.01) and
      being pregnant for the first time (OR = 6.82, 95% CI; 1.27-36.55). CONCLUSION:
      BPACR practice in the study area was found to be low. Effort to increase BPACR
      should focus on availing antenatal care services.

PMID- 21731748
TI  - Co-localization of the oncogenic transcription factor MYCN and the DNA methyl
      binding protein MeCP2 at genomic sites in neuroblastoma.
AB  - BACKGROUND: MYCN is a transcription factor that is expressed during the
      development of the neural crest and its dysregulation plays a major role in the
      pathogenesis of pediatric cancers such as neuroblastoma, medulloblastoma and
      rhabdomyosarcoma. MeCP2 is a CpG methyl binding protein which has been associated
      with a number of cancers and developmental disorders, particularly Rett syndrome.
      METHODS AND FINDINGS: Using an integrative global genomics approach involving
      chromatin immunoprecipitation applied to microarrays, we have determined that
      MYCN and MeCP2 co-localize to gene promoter regions, as well as inter/intragenic
      sites, within the neuroblastoma genome (MYCN amplified Kelly cells) at high
      frequency (70.2% of MYCN sites were also positive for MeCP2). Intriguingly, the
      frequency of co-localization was significantly less at promoter regions
      exhibiting substantial hypermethylation (8.7%), as determined by methylated DNA
      immunoprecipitation (MeDIP) applied to the same microarrays. Co
      immunoprecipitation of MYCN using an anti-MeCP2 antibody indicated that a
      MYCN/MeCP2 interaction occurs at protein level. mRNA expression profiling
      revealed that the median expression of genes with promoters bound by MYCN was
      significantly higher than for genes bound by MeCP2, and that genes bound by both
      proteins had intermediate expression. Pathway analysis was carried out for genes
      bound by MYCN, MeCP2 or MYCN/MeCP2, revealing higher order functions.
      CONCLUSIONS: Our results indicate that MYCN and MeCP2 protein interact and co
      localize to similar genomic sites at very high frequency, and that the patterns
      of binding of these proteins can be associated with significant differences in
      transcriptional activity. Although it is not yet known if this interaction
      contributes to neuroblastoma disease pathogenesis, it is intriguing that the
      interaction occurs at the promoter regions of several genes important for the
      development of neuroblastoma, including ALK, AURKA and BDNF.

PMID- 21731749
TI  - Molecular diet analysis of two african free-tailed bats (molossidae) using high
      throughput sequencing.
AB  - Given the diversity of prey consumed by insectivorous bats, it is difficult to
      discern the composition of their diet using morphological or conventional PCR
      based analyses of their faeces. We demonstrate the use of a powerful alternate
      tool, the use of the Roche FLX sequencing platform to deep-sequence uniquely 5'
      tagged insect-generic barcode cytochrome c oxidase I (COI) fragments, that were
      PCR amplified from faecal pellets of two free-tailed bat species Chaerephon
      pumilus and Mops condylurus (family: Molossidae). Although the analyses were
      challenged by the paucity of southern African insect COI sequences in the GenBank
      and BOLD databases, similarity to existing collections allowed the preliminary
      identification of 25 prey families from six orders of insects within the diet of
      C. pumilus, and 24 families from seven orders within the diet of M. condylurus.
      Insects identified to families within the orders Lepidoptera and Diptera were
      widely present among the faecal samples analysed. The two families that were
      observed most frequently were Noctuidae and Nymphalidae (Lepidoptera). Species
      level analysis of the data was accomplished using novel bioinformatics techniques
      for the identification of molecular operational taxonomic units (MOTU). Based on
      these analyses, our data provide little evidence of resource partitioning between
      sympatric M. condylurus and C. pumilus in the Simunye region of Swaziland at the
      time of year when the samples were collected, although as more complete databases
      against which to compare the sequences are generated this may have to be re
      evaluated.

PMID- 21731750
TI  - DNA methylation changes in atypical adenomatous hyperplasia, adenocarcinoma in
      situ, and lung adenocarcinoma.
AB  - BACKGROUND: Aberrant DNA methylation is common in lung adenocarcinoma, but its
      timing in the phases of tumor development is largely unknown. Delineating when
      abnormal DNA methylation arises may provide insight into the natural history of
      lung adenocarcinoma and the role that DNA methylation alterations play in tumor
      formation. METHODOLOGY/PRINCIPAL FINDINGS: We used MethyLight, a sensitive real
      time PCR-based quantitative method, to analyze DNA methylation levels at 15 CpG
      islands that are frequently methylated in lung adenocarcinoma and that we had
      flagged as potential markers for non-invasive detection. We also used two repeat
      probes as indicators of global DNA hypomethylation. We examined DNA methylation
      in 249 tissue samples from 93 subjects, spanning the putative spectrum of
      peripheral lung adenocarcinoma development: histologically normal adjacent non
      tumor lung, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS,
      formerly known as bronchioloalveolar carcinoma), and invasive lung
      adenocarcinoma. Comparison of DNA methylation levels between the lesion types
      suggests that DNA hypermethylation of distinct loci occurs at different time
      points during the development of lung adenocarcinoma. DNA methylation at CDKN2A
      ex2 and PTPRN2 is already significantly elevated in AAH, while CpG islands at
      2C35, EYA4, HOXA1, HOXA11, NEUROD1, NEUROD2 and TMEFF2 are significantly
      hypermethylated in AIS. In contrast, hypermethylation at CDH13, CDX2, OPCML,
      RASSF1, SFRP1 and TWIST1 and global DNA hypomethylation appear to be present
      predominantly in invasive cancer. CONCLUSIONS/SIGNIFICANCE: The gradual increase
      in DNA methylation seen for numerous loci in progressively more transformed
      lesions supports the model in which AAH and AIS are sequential stages in the
      development of lung adenocarcinoma. The demarcation of DNA methylation changes
      characteristic for AAH, AIS and adenocarcinoma begins to lay out a possible
      roadmap for aberrant DNA methylation events in tumor development. In addition, it
      identifies which DNA methylation changes might be used as molecular markers for
      the detection of preinvasive lesions.

PMID- 21731751
TI  - Inhibition of MLC phosphorylation restricts replication of influenza virus--a
      mechanism of action for anti-influenza agents.
AB  - Influenza A viruses are a severe threat worldwide, causing large epidemics that
      kill thousands every year. Prevention of influenza infection is complicated by
      continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK
      and protein kinase C inhibitors; however, the downstream effectors of these
      pathways have not been determined. In this study, we identified a common
      mechanism for the inhibitory effects of a significant group of anti-influenza
      agents. Our studies showed that influenza infection activates a series of
      signaling pathways that converge to induce myosin light chain (MLC)
      phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC
      phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C,
      and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation
      leads to the inhibition of influenza proliferation. In contrast, the induction of
      MLC phosphorylation enhances influenza proliferation, as does activation of the
      HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC
      phosphorylation. Additionally, in intracellular trafficking studies, we found
      that the nuclear export of influenza ribonucleoprotein depends on MLC
      phosphorylation. Our studies provide evidence that modulation of MLC
      phosphorylation is an underlying mechanism for the inhibitory effects of many
      anti-influenza compounds.

PMID- 21731752
TI  - The effects of cyclophosphamide on hippocampal cell proliferation and spatial
      working memory in rat.
AB  - Cyclophosphamide (CP) is a chemotherapy used in combinations that are associated
      with cognitive impairment. In the present study male Lister-hooded rats (n = 12)
      were used to investigate the effects of chronic administration of CP (30 mg/kg, 7
      i.v. doses, or an equivalent volume of saline) on performance in the novel
      location recognition (NLR) task and on the proliferation and survival of
      hippocampal cells. The survival of hippocampal cells dividing at the beginning of
      treatment was significantly reduced by CP. However, no difference was seen
      between CP treated and control groups for the number of cells proliferating 7
      days after the final injection and both groups performed equally well in the NLR
      task. These results indicate that the given dose of CP acutely reduces the
      survival of newly born hippocampal cells. However, it does not have a longer term
      effect on spatial working memory or hippocampal proliferation, suggesting that CP
      is less neurotoxic than other chemotherapies with which it is used in
      combination.

PMID- 21731753
TI  - Rapid detection of the H275Y oseltamivir resistance mutation in influenza A/H1N1
      2009 by single base pair RT-PCR and high-resolution melting.
AB  - INTRODUCTION: We aimed to design a real-time reverse-transcriptase-PCR (rRT-PCR),
      high-resolution melting (HRM) assay to detect the H275Y mutation that confers
      oseltamivir resistance in influenza A/H1N1 2009 viruses. FINDINGS: A novel
      strategy of amplifying a single base pair, the relevant SNP at position 823 of
      the neuraminidase gene, was chosen to maintain specificity of the assay. Wildtype
      and mutant virus were differentiated when using known reference samples of cell
      cultured virus. However, when dilutions of these reference samples were assayed,
      amplification of non-specific primer-dimer was evident and affected the overall
      melting temperature (T(m)) of the amplified products. Due to primer-dimer
      appearance at >30 cycles we found that if the cycle threshold (C(T)) for a
      dilution was >30, the HRM assay did not consistently discriminate mutant from
      wildtype. Where the C(T) was <30 we noted an inverse relationship between C(T)
      and T(m) and fitted quadratic curves allowed the discrimination of wildtype,
      mutant and 30?70 mutant?wildtype virus mixtures. We compared the C(T) values for
      a TaqMan H1N1 09 detection assay with those for the HRM assay using 59 clinical
      samples and demonstrated that samples with a TaqMan detection assay C(T)>32.98
      would have an H275Y assay C(T)>30. Analysis of the TaqMan C(T) values for 609
      consecutive clinical samples predicted that 207 (34%) of the samples would result
      in an HRM assay C(T)>30 and therefore not be amenable to the HRM assay.
      CONCLUSIONS: The use of single base pair PCR and HRM can be useful for
      specifically interrogating SNPs. When applied to H1N1 09, the constraints this
      placed on primer design resulted in amplification of primer-dimer products. The
      impact primer-dimer had on HRM curves was adjusted for by plotting T(m) against
      C(T). Although less sensitive than TaqMan assays, the HRM assay can rapidly, and
      at low cost, screen samples with moderate viral concentrations.

PMID- 21731754
TI  - Antidepressant-warfarin interaction and associated gastrointestinal bleeding risk
      in a case-control study.
AB  - BACKGROUND: Bleeding is the most common and worrisome adverse effect of warfarin
      therapy. One of the factors that might increase bleeding risk is initiation of
      interacting drugs that potentiate warfarin. We sought to evaluate whether
      initiation of an antidepressant increases the risk of hospitalization for
      gastrointestinal bleeding in warfarin users. METHODOLOGY/PRINCIPAL FINDINGS:
      Medicaid claims data (1999-2005) were used to perform an observational case
      control study nested within person-time exposed to warfarin in those >=18 years.
      In total, 430,455 warfarin users contributed 407,370 person-years of warfarin
      use. The incidence rate of hospitalization for GI bleeding among warfarin users
      was 4.48 per 100 person-years (95% CI, 4.42-4.55). Each gastrointestinal bleeding
      cases was matched to 50 controls based on index date and state. Warfarin users
      had an increased odds ratio of gastrointestinal bleeding upon initiation of
      citalopram (OR = 1.73 [95% CI, 1.25-2.38]), fluoxetine (OR = 1.63 [95% CI, 1.11
      2.38]), paroxetine (OR = 1.64 [95% CI, 1.27-2.12]), amitriptyline (OR = 1.47 [95%
      CI, 1.02-2.11]). Also mirtazapine, which is not believed to interact with
      warfarin, increased the risk of GI bleeding (OR = 1.75 [95% CI, 1.30-2.35]).
      CONCLUSIONS/SIGNIFICANCE: Warfarin users who initiated citalopram, fluoxetine,
      paroxetine, amitriptyline, or mirtazapine had an increased risk of
      hospitalization for gastrointestinal bleeding. However, the elevated risk with
      mirtazapine suggests that a drug-drug interaction may not have been responsible
      for all of the observed increased risk.

PMID- 21731755
TI  - PanSNPdb: the Pan-Asian SNP genotyping database.
AB  - The HUGO Pan-Asian SNP consortium conducted the largest survey to date of human
      genetic diversity among Asians by sampling 1,719 unrelated individuals among 71
      populations from China, India, Indonesia, Japan, Malaysia, the Philippines,
      Singapore, South Korea, Taiwan, and Thailand. We have constructed a database
      (PanSNPdb), which contains these data and various new analyses of them. PanSNPdb
      is a research resource in the analysis of the population structure of Asian
      peoples, including linkage disequilibrium patterns, haplotype distributions, and
      copy number variations. Furthermore, PanSNPdb provides an interactive comparison
      with other SNP and CNV databases, including HapMap3, JSNP, dbSNP and DGV and thus
      provides a comprehensive resource of human genetic diversity. The information is
      accessible via a widely accepted graphical interface used in many genetic
      variation databases. Unrestricted access to PanSNPdb and any associated files is
      available at: http://www4a.biotec.or.th/PASNP.

PMID- 21731756
TI  - Lipopolysaccharide renders transgenic mice expressing human serum amyloid P
      component sensitive to Shiga toxin 2.
AB  - Transgenic C57BL/6 mice expressing human serum amyloid P component (HuSAP) are
      resistant to Shiga toxin 2 (Stx2) at dosages that are lethal in HuSAP-negative
      wild-type mice. However, it is well established that Stx2 initiates extra
      intestinal complications such as the haemolytic-uremic syndrome despite the
      presence of HuSAP in human sera. We now demonstrate that co-administering
      purified Escherichia coli O55 lipopolysaccharide (LPS), at a dosage of 300 ng/g
      body weight, to HuSAP-transgenic mice increases their susceptibility to the
      lethal effects of Stx2. The enhanced susceptibility to Stx2 correlated with an
      increased expression of genes encoding the pro-inflammatory cytokine TNFalpha and
      chemokines of the CXC and CC families in the kidneys of LPS-treated mice, 48
      hours after the Stx2/LPS challenge. Co-administering the glucocorticoid
      dexamethasone, but not the LPS neutralizing cationic peptide LL-37, protected LPS
      sensitized HuSAP-transgenic mice from lethal doses of Stx2. Dexamethasone
      protection was specifically associated with decreased expression of the same
      inflammatory mediators (CXC and CC-type chemokines and TNFalpha) linked to
      enhanced susceptibility caused by LPS. The studies reveal further details about
      the complex cascade of host-related events that are initiated by Stx2 as well as
      establish a new animal model system in which to investigate strategies for
      diminishing serious Stx2-mediated complications in humans infected with
      enterohemorrhagic E. coli strains.

PMID- 21731757
TI  - Systemic signature of the lung response to respiratory syncytial virus infection.
AB  - Respiratory Syncytial Virus is a frequent cause of severe bronchiolitis in
      children. To improve our understanding of systemic host responses to RSV, we
      compared BALB/c mouse gene expression responses at day 1, 2, and 5 during primary
      RSV infection in lung, bronchial lymph nodes, and blood. We identified a set of
      53 interferon-associated and innate immunity genes that give correlated responses
      in all three murine tissues. Additionally, we identified blood gene signatures
      that are indicative of acute infection, secondary immune response, and vaccine
      enhanced disease, respectively. Eosinophil-associated ribonucleases were
      characteristic for the vaccine-enhanced disease blood signature. These results
      indicate that it may be possible to distinguish protective and unfavorable
      patient lung responses via blood diagnostics.

PMID- 21731758
TI  - TGF-beta-mediated sustained ERK1/2 activity promotes the inhibition of
      intracellular growth of Mycobacterium avium in epithelioid cells surrogates.
AB  - Transforming growth factor beta (TGF-beta) has been implicated in the
      pathogenesis of several diseases including infection with intracellular pathogens
      such as the Mycobacterium avium complex. Infection of macrophages with M. avium
      induces TGF-beta production and neutralization of this cytokine has been
      associated with decreased intracellular bacterial growth. We have previously
      demonstrated that epithelioid cell surrogates (ECs) derived from primary murine
      peritoneal macrophages through a process of differentiation induced by IL-4
      overlap several features of epithelioid cells found in granulomas. In contrast to
      undifferentiated macrophages, ECs produce larger amounts of TGF-beta and inhibit
      the intracellular growth of M. avium. Here we asked whether the levels of TGF
      beta produced by ECs are sufficient to induce a self-sustaining autocrine TGF
      beta signaling controlling mycobacterial replication in infected-cells. We showed
      that while exogenous addition of increased concentration of TGF-beta to infected
      macrophages counteracted M. avium replication, pharmacological blockage of TGF
      beta receptor kinase activity with SB-431542 augmented bacterial load in infected
      ECs. Moreover, the levels of TGF-beta produced by ECs correlated with high and
      sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126
      increased M. avium replication in infected-cells, suggesting that modulation of
      intracellular bacterial growth is dependent on the activation of ERK1/2.
      Interestingly, blockage of TGF-beta receptor kinase activity with SB-431542 in
      infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden
      and these effects were followed by a severe decrease in TGF-beta production. In
      summary, our findings indicate that the amplitude of TGF-beta signaling
      coordinates the strength and duration of ERK1/2 activity that is determinant for
      the control of intracellular mycobacterial growth.

PMID- 21731759
TI  - Notch, IL-1 and leptin crosstalk outcome (NILCO) is critical for leptin-induced
      proliferation, migration and VEGF/VEGFR-2 expression in breast cancer.
AB  - High levels of pro-angiogenic factors, leptin, IL-1, Notch and VEGF (ligands and
      receptors), are found in breast cancer, which is commonly correlated with
      metastasis and lower survival of patients. We have previously reported that
      leptin induces the growth of breast cancer and the expression of VEGF/VEGFR-2 and
      IL-1 system. We hypothesized that Notch, IL-1 and leptin crosstalk outcome
      (NILCO) plays an essential role in the regulation of leptin-mediated induction of
      proliferation/migration and expression of pro-angiogenic molecules in breast
      cancer. To test this hypothesis, leptin's effects on the expression and
      activation of Notch signaling pathway and VEGF/VEGFR-2/IL-1 were determined in
      mouse (4T1, EMT6 and MMT) breast cancer cells. Remarkably, leptin up-regulated
      Notch1-4/JAG1/Dll-4, Notch target genes: Hey2 and survivin, together with IL-1
      and VEGF/VEGFR-2. RNA knockdown and pharmacological inhibitors of leptin
      signaling significantly abrogated activity of reporter gene-luciferase CSL (RBP
      Jk) promoter, showing that it was linked to leptin-activated JAK2/STAT3, MAPK, PI
      3K/mTOR, p38 and JNK signaling pathways. Interestingly, leptin upregulatory
      effects on cell proliferation/migration and pro-angiogenic factors Notch, IL-1
      and VEGF/VEGFR-2 were abrogated by a gamma-secretase inhibitor, DAPT, as well as
      siRNA against CSL. In addition, blockade of IL-1R tI inhibited leptin-induced
      Notch, Hey2 and survivin as well as VEGF/VEGFR-2 expression. These data suggest
      leptin is an inducer of Notch (expression/activation) and IL-1 signaling
      modulates leptin effects on Notch and VEGF/VEGFR-2. We show for the first time
      that a novel unveiled crosstalk between Notch, IL-1 and leptin (NILCO) occurs in
      breast cancer. Leptin induction of proliferation/migration and upregulation of
      VEGF/VEGFR-2 in breast cancer cells were related to an intact Notch signaling
      axis. NILCO could represent the integration of developmental, pro-inflammatory
      and pro-angiogenic signals critical for leptin-induced cell
      proliferation/migration and regulation of VEGF/VEGFR-2 in breast cancer.
      Targeting NILCO might help to design new pharmacological strategies aimed at
      controlling breast cancer growth and angiogenesis.

PMID- 21731760
TI  - A novel missense mutation in the connexin30 causes nonsyndromic hearing loss.
AB  - Dysfunctional gap junctions caused by GJB2 (CX26) and GJB6 (CX30) mutations are
      implicated in nearly half of nonsyndromic hearing loss cases. A recent study
      identified a heterozygous mutation, c.119C>T (p.A40V), in the GJB6 gene of
      patients with nonsyndromic hearing loss. However, the functional role of the
      mutation in hearing loss remains unclear. In this study, analyses of cell biology
      indicated that a p.A40V missense mutation of CX30 causes CX30 protein
      accumulation in the Golgi body rather than in the cytoplasmic membrane. The tet
      on protein expression system was used for further study of mutant proteins in
      CX30 and CX30A40V co-expressions and in CX26 and CX30A40V co-expressions. The
      p.A40V missense mutation exerted a dominant negative effect on both normal CX30
      and CX26, which impaired gap junction formation. Moreover, computer-assisted
      modeling suggested that this p.A40V mutation affects the intra molecular
      interaction in the hydrophobic core of Trp44, which significantly alters the
      efficiency of gap junction formation. These findings suggest that the p.A40V
      mutation in CX30 causes autosomal-dominant nonsyndromic hearing loss. These data
      provide a novel molecular explanation for the role of GJB6 in hearing loss.

PMID- 21731761
TI  - Waterborne signaling primes the expression of elicitor-induced genes and buffers
      the oxidative responses in the brown alga Laminaria digitata.
AB  - As marine sessile organisms, seaweeds must respond efficiently to biotic and
      abiotic challenges in their natural environment to reduce the fitness
      consequences of wounds and oxidative stress. This study explores the early steps
      of the defense responses of a large marine brown alga (the tangle kelp Laminaria
      digitata) and investigates its ability to transmit a warning message to
      neighboring conspecifics. We compared the early responses to elicitation with
      oligoguluronates in laboratory-grown and harvested wild individuals of L.
      digitata. We followed the release of H2O2 and the concomitant production of
      volatile organic compounds. We also monitored the kinetics of expression of
      defense-related genes following the oxidative burst. Laboratory-grown algae were
      transplanted in kelp habitats to further evaluate their responses to elicitation
      after a transient immersion in natural seawater. In addition, a novel
      conditioning procedure was established to mimic field conditions in the
      laboratory. Our experiments showed that L. digitata integrates waterborne cues
      present in the kelp bed and/or released from elicited neighboring plants. Indeed,
      the exposure to elicited conspecifics changes the patterns of oxidative burst and
      volatile emissions and potentiates this kelp for faster induction of genes
      specifically regulated in response to oligoguluronates. Thus, waterborne signals
      shape the elicitor-induced responses of kelps through a yet unknown mechanism
      reminiscent of priming in land plants.

PMID- 21731762
TI  - Caspase-1 dependent IL-1beta secretion is critical for host defense in a mouse
      model of Chlamydia pneumoniae lung infection.
AB  - Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical
      pneumonia and is associated with various chronic inflammatory disorders. Caspase
      1 is a key component of the 'inflammasome', and is required to cleave pro-IL
      1beta to bioactive IL-1beta. Here we demonstrate for the first time a critical
      requirement for IL-1beta in response to CP infection. Caspase-1-/- mice exhibit
      delayed cytokine production, defective clearance of pulmonary bacteria and higher
      mortality in response to CP infection. Alveolar macrophages harbored increased
      bacterial numbers due to reduced iNOS levels in Caspase-1-/- mice.
      Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice
      phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1beta
      rescues CP infected Caspase-1-/- mice from mortality, indicating that IL-1beta
      secretion is crucial for host immune defense against CP lung infection. In vitro
      investigation reveals that CP-induced IL-1beta secretion by macrophages requires
      TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new
      protein synthesis by CP are required for inflammasome activation. Neither ROS nor
      cathepsin was required for CP infection induced inflammasome activation.
      Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial
      dysfunction indicating a possible mechanism involving the mitochondria for CP
      induced inflammasome activation.

PMID- 21731763
TI  - Genetic and molecular characterization of flagellar assembly in Shewanella
      oneidensis.
AB  - Shewanella oneidensis is a highly motile organism by virtue of a polar flagellum.
      Unlike most flagellated bacteria, it contains only one major chromosome segment
      encoding the components of the flagellum with the exception of the motor
      proteins. In this region, three genes encode flagellinsaccording to the original
      genome annotation. However, we find that only flaA and flaB encode functional
      filament subunits. Although these two genesare under the control of different
      promoters, they are actively transcribed and subsequently translated, producing a
      considerable number of flagellin proteins. Additionally, both flagellins are able
      to interact with their chaperon FliS and are subjected to feedback regulation.
      Furthermore, FlaA and FlaB are glycosylated by a pathwayinvolving a major
      glycosylating enzyme,PseB, in spite of the lack of the majority of theconsensus
      glycosylation sites. In conclusion, flagellar assembly in S. oneidensis has novel
      features despite the conservation of homologous genes across taxa.

PMID- 21731764
TI  - Dynamics of airborne influenza A viruses indoors and dependence on humidity.
AB  - There is mounting evidence that the aerosol transmission route plays a
      significant role in the spread of influenza in temperate regions and that the
      efficiency of this route depends on humidity. Nevertheless, the precise
      mechanisms by which humidity might influence transmissibility via the aerosol
      route have not been elucidated. We hypothesize that airborne concentrations of
      infectious influenza A viruses (IAVs) vary with humidity through its influence on
      virus inactivation rate and respiratory droplet size. To gain insight into the
      mechanisms by which humidity might influence aerosol transmission, we modeled the
      size distribution and dynamics of IAVs emitted from a cough in typical
      residential and public settings over a relative humidity (RH) range of 10-90%.
      The model incorporates the size transformation of virus-containing droplets due
      to evaporation and then removal by gravitational settling, ventilation, and virus
      inactivation. The predicted concentration of infectious IAVs in air is 2.4 times
      higher at 10% RH than at 90% RH after 10 min in a residential setting, and this
      ratio grows over time. Settling is important for removal of large droplets
      containing large amounts of IAVs, while ventilation and inactivation are
      relatively more important for removal of IAVs associated with droplets <5 um. The
      inactivation rate increases linearly with RH; at the highest RH, inactivation can
      remove up to 28% of IAVs in 10 min. Humidity is an important variable in aerosol
      transmission of IAVs because it both induces droplet size transformation and
      affects IAV inactivation rates. Our model advances a mechanistic understanding of
      the aerosol transmission route, and results complement recent studies on the
      relationship between humidity and influenza's seasonality. Maintaining a high
      indoor RH and ventilation rate may help reduce chances of IAV infection.

PMID- 21731765
TI  - Vitamin D status and bone and connective tissue turnover in brown bears (Ursus
      arctos) during hibernation and the active state.
AB  - BACKGROUND: Extended physical inactivity causes disuse osteoporosis in humans. In
      contrast, brown bears (Ursus arctos) are highly immobilised for half of the year
      during hibernation without signs of bone loss and therefore may serve as a model
      for prevention of osteoporosis. AIM: To study 25-hydroxy-vitamin D (25OHD) levels
      and bone turnover markers in brown bears during the hibernating state in winter
      and during the active state in summer. We measured vitamin D subtypes (D2 and
      D3), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D
      [1,25(OH)2D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum
      calcium and PIIINP. MATERIAL AND METHODS: We drew blood from seven immobilised
      wild brown bears during hibernation in February and in the same bears while
      active in June. RESULTS: Serum 25-hydroxy-cholecalciferol (25OHD3) was
      significantly higher in the summer than in the winter (22.8+/-4.6 vs. 8.8+/-2.1
      nmol/l, two tailed p-2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD2) was
      higher in winter (54.2+/-8.3 vs. 18.7+/-1.7 nmol/l, 2p<0.01). Total serum calcium
      and PTH levels did not differ between winter and summer. Activated 1,25(OH)2D
      demonstrated a statistically insignificant trend towards higher summer levels.
      Osteocalcin levels were higher in summer than winter, whereas other markers of
      bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of
      connective tissue and to some degree muscle turnover, was significantly higher
      during summer than during winter. CONCLUSIONS: Dramatic changes were documented
      in the vitamin D3/D2 ratio and in markers of bone and connective tissue turnover
      in brown bears between hibernation and the active state. Because hibernating
      brown bears do not develop disuse osteoporosis, despite extensive physical
      inactivity we suggest that they may serve as a model for the prevention of this
      disease.

PMID- 21731766
TI  - Suppression of STAT3 and HIF-1 alpha mediates anti-angiogenic activity of
      betulinic acid in hypoxic PC-3 prostate cancer cells.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is a
      transcription factor that regulates various cellular processes such as cell
      survival, angiogenesis and proliferation. In the present study, we examined that
      betulinic acid (BA), a triterpene from the bark of white birch, had the
      inhibitory effects on hypoxia-mediated activation of STAT3 in androgen
      independent human prostate cancer PC-3 cells. METHODOLOGY/PRINCIPAL FINDINGS: BA
      inhibited the protein expression and the transcriptional activities of hypoxia
      inducible factor-1alpha (HIF-1alpha) under hypoxic condition. Consistently, BA
      blocked hypoxia-induced phosphorylation, DNA binding activity and nuclear
      accumulation of STAT3. In addition, BA significantly reduced cellular and
      secreted levels of vascular endothelial growth factor (VEGF), a critical
      angiogenic factor and a target gene of STAT3 induced under hypoxia. Furthermore,
      BA prevented in vitro capillary tube formation in human umbilical vein
      endothelial cells (HUVECs) maintained in conditioned medium of hypoxic PC-3
      cells, implying anti-angiogenic activity of BA under hypoxic condition. Of note,
      chromatin immunoprecipitation (ChiP) assay revealed that BA inhibited binding of
      HIF-1alpha and STAT3 to VEGF promoter. Furthermore, silencing STAT3 using siRNA
      transfection effectively enhanced the reduced VEGF production induced by BA
      treatment under hypoxia. CONCLUSIONS/SIGNIFICANCE: Taken together, our results
      suggest that BA has anti-angiogenic activity by disturbing the binding of HIF
      1alpha and STAT3 to the VEGF promoter in hypoxic PC-3 cells.

PMID- 21731767
TI  - MicroRNA expression profiling reveals miRNA families regulating specific
      biological pathways in mouse frontal cortex and hippocampus.
AB  - MicroRNAs (miRNAs) are small regulatory molecules that cause post-transcriptional
      gene silencing. Although some miRNAs are known to have region-specific expression
      patterns in the adult brain, the functional consequences of the region
      specificity to the gene regulatory networks of the brain nuclei are not clear.
      Therefore, we studied miRNA expression patterns by miRNA-Seq and microarrays in
      two brain regions, frontal cortex (FCx) and hippocampus (HP), which have separate
      biological functions. We identified 354 miRNAs from FCx and 408 from HP using
      miRNA-Seq, and 245 from FCx and 238 from HP with microarrays. Several miRNA
      families and clusters were differentially expressed between FCx and HP, including
      the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster
      overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the
      clusters, we developed support for viewing genomic alignments of miRNA-Seq reads
      in the Chipster genome browser. We carried out pathway analysis of the predicted
      target genes of differentially expressed miRNA families and clusters to assess
      their putative biological functions. Interestingly, several miRNAs from the same
      family/cluster were predicted to regulate specific biological pathways. We have
      developed a miRNA-Seq approach with a bioinformatic analysis workflow that is
      suitable for studying miRNA expression patterns from specific brain nuclei. FCx
      and HP were shown to have distinct miRNA expression patterns which were reflected
      in the predicted gene regulatory pathways. This methodology can be applied for
      the identification of brain region-specific and phenotype-specific miRNA-mRNA
      regulatory networks from the adult and developing rodent brain.

PMID- 21731768
TI  - Functional analysis of conserved non-coding regions around the short stature hox
      gene (shox) in whole zebrafish embryos.
AB  - BACKGROUND: Mutations in the SHOX gene are responsible for Leri-Weill
      Dyschondrosteosis, a disorder characterised by mesomelic limb shortening. Recent
      investigations into regulatory elements surrounding SHOX have shown that
      deletions of conserved non-coding elements (CNEs) downstream of the SHOX gene
      produce a phenotype indistinguishable from Leri-Weill Dyschondrosteosis. As this
      gene is not found in rodents, we used zebrafish as a model to characterise the
      expression pattern of the shox gene across the whole embryo and characterise the
      enhancer domains of different CNEs associated with this gene.
      METHODOLOGY/PRINCIPAL FINDINGS: Expression of the shox gene in zebrafish was
      identified using in situ hybridization, with embryos showing expression in the
      blood, putative heart, hatching gland, brain pharyngeal arch, olfactory
      epithelium, and fin bud apical ectodermal ridge. By identifying sequences showing
      65% identity over at least 40 nucleotides between Fugu, human, dog and opossum we
      uncovered 35 CNEs around the shox gene. These CNEs were compared with CNEs
      previously discovered by Sabherwal et al., resulting in the identification of
      smaller more deeply conserved sub-sequence. Sabherwal et al.'s CNEs were assayed
      for regulatory function in whole zebrafish embryos resulting in the
      identification of additional tissues under the regulatory control of these CNEs.
      CONCLUSION/SIGNIFICANCE: Our results using whole zebrafish embryos have provided
      a more comprehensive picture of the expression pattern of the shox gene, and a
      better understanding of its regulation via deeply conserved noncoding elements.
      In particular, we identify additional tissues under the regulatory control of
      previously identified SHOX CNEs. We also demonstrate the importance of these CNEs
      in evolution by identifying duplicated shox CNEs and more deeply conserved sub
      sequences within already identified CNEs.

PMID- 21731769
TI  - Grouper as a natural biocontrol of invasive lionfish.
AB  - Lionfish (Pterois volitans/miles) have invaded the majority of the Caribbean
      region within five years. As voracious predators of native fishes with a broad
      habitat distribution, lionfish are poised to cause an unprecedented disruption to
      coral reef diversity and function. Controls of lionfish densities within its
      native range are poorly understood, but they have been recorded in the stomachs
      of large-bodied Caribbean groupers. Whether grouper predation of lionfish is
      sufficient to act as a biocontrol of the invasive species is unknown, but pest
      biocontrol by predatory fishes has been reported in other ecosystems. Groupers
      were surveyed along a chain of Bahamian reefs, including one of the region's most
      successful marine reserves which supports the top one percentile of Caribbean
      grouper biomass. Lionfish biomass exhibited a 7-fold and non-linear reduction in
      relation to the biomass of grouper. While Caribbean grouper appear to be a
      biocontrol of invasive lionfish, the overexploitation of their populations by
      fishers, means that their median biomass on Caribbean reefs is an order of
      magnitude less than in our study. Thus, chronic overfishing will probably prevent
      natural biocontrol of lionfishes in the Caribbean.

PMID- 21731770
TI  - Three-dimensional X-ray observation of atmospheric biological samples by linear
      array scanning-electron generation X-ray microscope system.
AB  - Recently, we developed a soft X-ray microscope called the scanning-electron
      generation X-ray microscope (SGXM), which consists of a simple X-ray detection
      system that detects X-rays emitted from the interaction between a scanning
      electron beam (EB) and the thin film of the sample mount. We present herein a
      three-dimensional (3D) X-ray detection system that is based on the SGXM
      technology and designed for studying atmospheric biological samples. This 3D X
      ray detection system contains a linear X-ray photodiode (PD) array. The specimens
      are placed under a CuZn-coated Si3N4 thin film, which is attached to an
      atmospheric sample holder. Multiple tilt X-ray images of the samples are detected
      simultaneously by the linear array of X-ray PDs, and the 3D structure is
      calculated by a new 3D reconstruction method that uses a simulated-annealing
      algorithm. The resulting 3D models clearly reveal the inner structure of the
      bacterium. In addition, the proposed method can easily be used for diverse
      samples in a broad range of scientific fields.

PMID- 21731771
TI  - Altered error processing following vascular thalamic damage: evidence from an
      antisaccade task.
AB  - Event-related potentials (ERP) research has identified a negative deflection
      within about 100 to 150 ms after an erroneous response--the error-related
      negativity (ERN)--as a correlate of awareness-independent error processing. The
      short latency suggests an internal error monitoring system acting rapidly based
      on central information such as an efference copy signal. Studies on monkeys and
      humans have identified the thalamus as an important relay station for efference
      copy signals of ongoing saccades. The present study investigated error processing
      on an antisaccade task with ERPs in six patients with focal vascular damage to
      the thalamus and 28 control subjects. ERN amplitudes were significantly reduced
      in the patients, with the strongest ERN attenuation being observed in two
      patients with right mediodorsal and ventrolateral and bilateral ventrolateral
      damage, respectively. Although the number of errors was significantly higher in
      the thalamic lesion patients, the degree of ERN attenuation did not correlate
      with the error rate in the patients. The present data underline the role of the
      thalamus for the online monitoring of saccadic eye movements, albeit not
      providing unequivocal evidence in favour of an exclusive role of a particular
      thalamic site being involved in performance monitoring. By relaying saccade
      related efference copy signals, the thalamus appears to enable fast error
      processing. Furthermore early error processing based on internal information may
      contribute to error awareness which was reduced in the patients.

PMID- 21731772
TI  - Molecular implication of PP2A and Pin1 in the Alzheimer's disease specific
      hyperphosphorylation of Tau.
AB  - BACKGROUND: Tau phosphorylation and dephosphorylation regulate in a poorly
      understood manner its physiological role of microtubule stabilization, and
      equally its integration in Alzheimer disease (AD) related fibrils. A specific
      phospho-pattern will result from the balance between kinases and phosphatases.
      The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit
      PR55/Balpha (PP2A(T55alpha)) is a major Tau phosphatase in vivo, which
      contributes to its final phosphorylation state. We use NMR spectroscopy to
      determine the dephosphorylation rates of phospho-Tau by this major brain
      phosphatase, and present site-specific and kinetic data for the individual sites
      including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes.
      METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate the importance of the PR55/Balpha
      regulatory subunit of PP2A within this enzymatic process, and show that,
      unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with
      the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be
      released by the phosphorylation dependent prolyl cis/trans isomerase Pin1.
      Because the stimulatory effect is lost with the dimeric PP2A core enzyme
      (PP2A(D)) or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the
      interaction between the PR55/Balpha subunit and the AT180 phospho-epitope on Tau.
      CONCLUSIONS/SIGNIFICANCE: Our results show that phosphorylation of T231 (AT180)
      can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope,
      even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231
      AT180 is required for efficient PP2A(T55alpha)-mediated dephosphorylation of
      pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported
      for certain Tau kinases and the one described here for Tau phosphatase
      PP2A(T55alpha) may contribute to the hyperphosphorylation of Tau observed in AD
      neurons.

PMID- 21731773
TI  - Mechanism of heparin acceleration of tissue inhibitor of metalloproteases-1 (TIMP
      1) degradation by the human neutrophil elastase.
AB  - Heparin has been shown to regulate human neutrophil elastase (HNE) activity. We
      have assessed the regulatory effect of heparin on Tissue Inhibitor of
      Metalloproteases-1 [TIMP-1] hydrolysis by HNE employing the recombinant form of
      TIMP-1 and correlated FRET-peptides comprising the TIMP-1 cleavage site. Heparin
      accelerates 2.5-fold TIMP-1 hydrolysis by HNE. The kinetic parameters of this
      reaction were monitored with the aid of a FRET-peptide substrate that mimics the
      TIMP-1 cleavage site in pre-steady-state conditionsby using a stopped-flow
      fluorescence system. The hydrolysis of the FRET-peptide substrate by HNE exhibits
      a pre-steady-state burst phase followed by a linear, steady-state pseudo-first
      order reaction. The HNE acylation step (k2 = 21+/-1 s-1) was much higher than the
      HNE deacylation step (k3 = 0.57+/-0.05 s-1). The presence of heparin induces a
      dramatic effect in the pre-steady-state behavior of HNE. Heparin induces
      transient lag phase kinetics in HNE cleavage of the FRET-peptide substrate. The
      pre-steady-state analysis revealed that heparin affects all steps of the reaction
      through enhancing the ES complex concentration, increasing k1 2.4-fold and
      reducing k-1 3.1-fold. Heparin also promotes a 7.8-fold decrease in the k2 value,
      whereas the k3 value in the presence of heparin was increased 58-fold. These
      results clearly show that heparin binding accelerates deacylation and slows down
      acylation. Heparin shifts the HNE pH activity profile to the right, allowing HNE
      to be active at alkaline pH. Molecular docking and kinetic analysis suggest that
      heparin induces conformational changes in HNE structure. Here, we are showing for
      the first time that heparin is able to accelerate the hydrolysis of TIMP-1 by
      HNE. The degradation of TIMP-1is associated to important physiopathological
      states involving excessive activation of MMPs.

PMID- 21731774
TI  - Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43
      revealed by MD simulations.
AB  - The gap junction protein connexin43 (Cx43) binds to the second PDZ domain of
      Zonula occludens-1 (ZO-1) through its C-terminal tail, mediating the regulation
      of gap junction plaque size and dynamics. Biochemical study demonstrated that the
      very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2
      binding and phosphorylation at residues Ser (-9) and Ser (-10) of the peptide can
      disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in
      complex with a shorter 9 aa peptide of connexin43 was solved experimentally.
      Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated
      Cx43 peptides were studied using molecular dynamics (MD) simulations and free
      energy calculation. The short peptide bound to PDZ2 exhibits large structural
      variations, while the extension of three upstream residues stabilizes the peptide
      conformation and enhanced the interaction. Phosphorylation at Ser(-9)
      significantly weakens the binding and results in conformational flexibility of
      the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43
      binding and phosphorylation induced dissociation.

PMID- 21731775
TI  - Vesicoureteral reflux and other urinary tract malformations in mice compound
      heterozygous for Pax2 and Emx2.
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common
      cause of chronic kidney disease in children. This disease group includes a
      spectrum of urinary tract defects including vesicoureteral reflux, duplex kidneys
      and other developmental defects that can be found alone or in combination. To
      identify new regulators of CAKUT, we tested the genetic cooperativity between
      several key regulators of urogenital system development in mice. We found a high
      incidence of urinary tract anomalies in Pax2;Emx2 compound heterozygous mice that
      are not found in single heterozygous mice. Pax2+/-;Emx2+/- mice harbor duplex
      systems associated with urinary tract obstruction, bifid ureter and a high
      penetrance of vesicoureteral reflux. Remarkably, most compound heterozygous mice
      refluxed at low intravesical pressure. Early analysis of Pax2+/-;Emx2+/- embryos
      point to ureter budding defects as the primary cause of urinary tract anomalies.
      We additionally establish Pax2 as a direct regulator of Emx2 expression in the
      Wolffian duct. Together, these results identify a haploinsufficient genetic
      combination resulting in CAKUT-like phenotype, including a high sensitivity to
      vesicoureteral reflux. As both genes are located on human chromosome 10q, which
      is lost in a proportion of VUR patients, these findings may help understand VUR
      and CAKUT in humans.

PMID- 21731776
TI  - Evolutionary analysis of novel serine proteases in the venom gland transcriptome
      of Bitis gabonica rhinoceros.
AB  - BACKGROUND: Serine proteases are major components of viper venom and target
      various stages of the blood coagulation system in victims and prey. A better
      understanding of the diversity of serine proteases and other enzymes present in
      snake venom will help to understand how the complexity of snake venom has evolved
      and will aid the development of novel therapeutics for treating snake bites.
      METHODOLOGY AND PRINCIPAL FINDINGS: Four serine protease-encoding genes from the
      venom gland transcriptome of Bitis gabonica rhinoceros were amplified and
      sequenced. Mass spectrometry suggests the four enzymes corresponding to these
      genes are present in the venom of B. g. rhinoceros. Two of the enzymes,
      rhinocerases 2 and 3 have substitutions to two of the serine protease catalytic
      triad residues and are thus unlikely to be catalytically active, though they may
      have evolved other toxic functions. The other two enzymes, rhinocerases 4 and 5,
      have classical serine protease catalytic triad residues and thus are likely to be
      catalytically active, however they have glycine rather than the more typical
      aspartic acid at the base of the primary specificity pocket (position 189). Based
      on a detailed analysis of these sequences we suggest that alternative splicing
      together with individual amino acid mutations may have been involved in their
      evolution. Changes within amino acid segments which were previously proposed to
      undergo accelerated change in venom serine proteases have also been observed.
      CONCLUSIONS AND SIGNIFICANCE: Our study provides further insight into the
      diversity of serine protease isoforms present within snake venom and discusses
      their possible functions and how they may have evolved. These multiple serine
      protease isoforms with different substrate specificities may enhance the
      envenomation effects and help the snake to adapt to new habitats and diets. Our
      findings have potential for helping the future development of improved
      therapeutics for snake bites.

PMID- 21731777
TI  - Increased infarct wall thickness by a bio-inert material is insufficient to
      prevent negative left ventricular remodeling after myocardial infarction.
AB  - BACKGROUND: Several injectable materials have been shown to preserve or improve
      cardiac function as well as prevent or slow left ventricular (LV) remodeling post
      myocardial infarction (MI). However, it is unclear as to whether it is the
      structural support or the bioactivity of these polymers that lead to beneficial
      effects. Herein, we examine how passive structural enhancement of the LV wall by
      an increase in wall thickness affects cardiac function post-MI using a bio-inert,
      non-degradable synthetic polymer in an effort to better understand the mechanisms
      by which injectable materials affect LV remodeling. METHODS AND RESULTS:
      Poly(ethylene glycol) (PEG) gels of storage modulus G' = 0.5+/-0.1 kPa were
      injected and polymerized in situ one week after total occlusion of the left
      coronary artery in female Sprague Dawley rats. The animals were imaged using
      magnetic resonance imaging (MRI) at 7+/-1 day(s) post-MI as a baseline and again
      post-injection 49+/-4 days after MI. Infarct wall thickness was statistically
      increased in PEG gel injected vs. control animals (p<0.01). However, animals in
      the polymer and control groups showed decreases in cardiac function in terms of
      end diastolic volume, end systolic volume and ejection fraction compared to
      baseline (p<0.01). The cellular response to injection was also similar in both
      groups. CONCLUSION: The results of this study demonstrate that passive structural
      reinforcement alone was insufficient to prevent post-MI remodeling, suggesting
      that bioactivity and/or cell infiltration due to degradation of injectable
      materials are likely playing a key role in the preservation of cardiac function,
      thus providing a deeper understanding of the influencing properties of
      biomaterials necessary to prevent post-MI negative remodeling.

PMID- 21731778
TI  - Functional expression of spider neurotoxic peptide huwentoxin-I in E. coli.
AB  - The coding sequence of huwentoxin-I, a neurotoxic peptide isolated from the venom
      of the Chinese spider Ornithoctonus huwena, was amplified by PCR using the cDNA
      library constructed from the spider venom glands. The cloned fragment was
      inserted into the expression vector pET-40b and transformed into the E. coli
      strain BL21 (DE3). The expression of a soluble fusion protein, disulfide
      interchange protein (DsbC)-huwentoxin-I, was auto-induced in the periplasm of E.
      coli in the absence of IPTG. After partial purification using a Ni-NTA column,
      the expressed fusion protein was digested using enterokinase to release
      heteroexpressed huwentoxin-I and was further purified using RP-HPLC. The
      resulting peptide was subjected to gel electrophoresis and mass spectrometry
      analysis. The molecular weight of the heteroexpressed huwentoxin-I was 3750.69,
      which is identical to that of the natural form of the peptide isolated from
      spider venom. The physiological properties of the heteroexpressed huwentoxin-I
      were further analyzed using a whole-cell patch clamp assay. The heteroexpressed
      huwentoxin-I was able to block currents generated by human Na(v1.7) at an IC50 of
      640 nmole/L, similar to that of the natural huwentoxin-I, which is 630 nmole/L.

PMID- 21731779
TI  - Using policy to strengthen the reach and impact of injury prevention efforts.

PMID- 21731780
TI  - Approaching Injury and Violence Prevention through Public Health Policy: A Window
      of Opportunity to Renew Our Focus.

PMID- 21731781
TI  - Systems thinking in injury prevention: an innovative model for informing state
      and local policies.

PMID- 21731782
TI  - Adoption of the 2006 field triage decision scheme for injured patients.
AB  - BACKGROUND: When emergency medical services (EMS) providers respond to the scene
      of an injury, they must decide where to transport the injured patients for
      further evaluation and treatment. This is done through a process known as "field
      triage", whereby a patient's injuries are matched to the most appropriate
      hospital. In 2005-2006 the National Expert Panel on Field Triage, convened by the
      Centers for Disease Control and Prevention and the National Highway Traffic
      Safety Administration, revised the 1999 American College of Surgeons Committee on
      Trauma Field Triage Decision Scheme. This revision, the 2006 Field Triage
      Decision Scheme, was published in 2006. METHODS: State Public Health departments'
      and EMS' external websites were evaluated to ascertain the current status of
      implementation of the 2006 Field Triage Decision Scheme. RESULTS: Information
      regarding field triage was located for 41 states. In nine states no information
      regarding field triage was available on their websites. Of the 41 states where
      information was located, seven were classified as "full adopters" of the 2006
      Field Triage Decision Scheme; nine were considered "partial adopters"; 17 states
      were found to be using a full version or modification of the 1999 Field Triage
      Decision Scheme; and eight states were considered to be using a different
      protocol or scheme for field triage. CONCLUSION: Many states have adopted the
      2006 Decision Scheme (full or partial). Further investigation is needed to
      determine the reasons why some states do not adopt the guidelines.

PMID- 21731783
TI  - Suburban Poverty: Barriers to Services and Injury Prevention among Marginalized
      Women who Use Methamphetamine.
AB  - OBJECTIVE: This paper aims to identify the needed healthcare and social services
      barriers for women living in suburban communities who are using or have used
      methamphetamine. Drug users are vulnerable to injury, violence and transmission
      of infectious diseases, and having access to healthcare has been shown to
      positively influence prevention and intervention among this population. Yet
      little is known regarding the social context of suburban drug users, their risks
      behaviors, and their access to healthcare. METHODS: The data collection involved
      participant observation in the field, face-to-face interviews and focus groups.
      Audio-recorded in-depth life histories, drug use histories, and resource needs
      were collected from 31 suburban women who were former or current users of
      methamphetamine. The majority was drawn from marginalized communities and highly
      vulnerable to risk for injury and violence. We provided these women with
      healthcare and social service information and conducted follow-up interviews to
      identify barriers to these services. RESULTS: Barriers included (1) restrictions
      imposed by the services and (2) limitations inherent in the women's social,
      economic, or legal situations. We found that the barriers increased the women's
      risk for further injury, violence and transmission of infectious diseases. Women
      who could not access needed healthcare and social resources typically used street
      drugs that were accessible and affordable to self-medicate their untreated
      emotional and physical pain. CONCLUSION: Our findings add to the literature on
      how healthcare and social services are related to injury prevention. Social
      service providers in the suburbs were often indifferent to the needs of drug
      using women. For these women, health services were accessed primarily at
      emergency departments (ED). To break the cycle of continued drug use, violence
      and injury, we suggest that ED staff be trained to perform substance abuse
      assessments and provide immediate referral to detoxification and treatment
      facilities. Policy change is needed for EDs to provide the care and linkages to
      treatment that can prevent future injuries and the spread of infectious diseases.

PMID- 21731784
TI  - Injury secondary to antiretroviral agents: retrospective analysis of a regional
      poison center database.
AB  - INTRODUCTION: Poisoning is an increasingly important cause of injury in the
      United States. In 2009 poison centers received 2,479,355 exposure reports,
      underscoring the role of poison centers in intentional and unintentional injury
      prevention. Antiretroviral (ARV) agents are commonly prescribed drugs known to
      cause toxicity, yet the frequency of these incidents is unknown. The objectives
      of this study were to quantify the number of reported cases of toxicity secondary
      to ARV agents at a regional poison center, and to describe the circumstances and
      clinical manifestations of these poisonings. METHODS: We conducted a
      retrospective review of poison center records between December 1, 2001, and
      January 7, 2010. RESULTS: One hundred sixty-two exposures to ARV agents were
      reported to the poison center, of which 30% were intentional and 70% were
      unintentional. Three patients developed major toxicity and no deaths occurred.
      The remaining patients developed moderate and minor effects as defined by poison
      center guidelines. CONCLUSION: ARV drug toxicity appears to be infrequently
      reported to the poison center. Fatal and major toxicities are uncommon, and
      intentional overdoses are associated with a more serious toxicity. Educational
      efforts should encourage clinicians to report toxicities related to the use of
      ARV agents to poison centers in order to better study this problem.

PMID- 21731785
TI  - Intentional ethylene glycol poisoning increase after media coverage of antifreeze
      murders.
AB  - BACKGROUND: The media can have a profound impact on human behavior. A sensational
      murder by ethylene glycol (EG) poisoning occurred in our state. The regional
      media provided extensive coverage of the murder. We undertook this investigation
      to evaluate our incidence of EG poisoning during the timeframe of before the
      first report linking a death to ethylene glycol to shortly after the first murder
      trial. METHODS: Descriptive statistics and linear regression were used to
      describe and analyze the number of EG cases over time. A search of the leading
      regional newspaper's archives established the media coverage timeline. RESULT:
      Between 2000 and 2004, our poison center (PC) handled a steady volume of
      unintentional exposures to EG [range: 105-123 per year, standard deviation
      (SD)=7.22]. EG exposures thought to be suicidal in intent increased from 12 cases
      in 2000 to 121 cases in 2004. In the 19 months prior to the first media report of
      this story, our PC handled a mean of 1 EG case with suicidal intent per month
      [range: 0-2, SD=.69]. In the month after the first media report, our PC handled 5
      EG cases with suicidal intent. When media coverage was most intense (2004), our
      PC received a mean of 10 EG suicidal-intent calls per month [range: 5-17,
      SD=3.55]. Although uncommon, reports of malicious EG poisonings also increased
      during this same period from 2 in 2000 to 14 in 2004. CONCLUSION: Media coverage
      of stories involving poisonings may result in copycat events, applicable to both
      self-poisonings and concern for malicious poisonings. Poison centers should be
      aware of this phenomenon, pay attention to local media and plan accordingly if a
      poisoning event receives significant media coverage. The media should be more
      sensitive to the content of their coverage and avoid providing "how to" poisoning
      information.

PMID- 21731786
TI  - Suicide fads: frequency and characteristics of hydrogen sulfide suicides in the
      United States.
AB  - OBJECTIVE: To assess the frequency of hydrogen sulfide (H(2)S) suicides and
      describe the characteristics of victims in the United States (U.S.) since the
      technique became common in Japan in 2007. METHODS: To ascertain the frequency of
      intentional H(2)S related deaths in the U.S. prior to the start of the Japanese
      trend in 2007, we searched the multiple-cause-of-death data from the National
      Vital Statistics System. To collect as much information about the victims as
      possible, we sent an email to the National Association of Medical Examiners
      (NAME) listserv asking for their cooperation in identifying cases of H(2)S
      suicide. To identify cases that were not voluntarily reported by medical
      examiners but were reported by the media, we conducted Google searches using the
      search terms: "hydrogen sulfide suicide," "H(2)S suicide," "detergent suicide,"
      "chemical suicide," and "suicide fad." We obtained all available autopsy reports
      and abstracted information, including the site of the incident, the presence of a
      note warning others about the toxic gas and the demographic characteristics of
      the victims. We contacted medical examiners who potentially had custody of the
      cases that were identified through media reports and requested autopsies of these
      victims. When unable to obtain the autopsies, we gathered information from the
      media reports. RESULTS: Forty-five deaths from H(2)S exposure occurred in the
      U.S. from 1999 to 2007, all unintentional. Responses from the NAME listserv
      yielded autopsy reports for 11 victims, and Google searches revealed an
      additional 19 H(2)S suicides in the U.S. since 2008. Overall (n=30), two cases
      were identified during 2008, 10 in 2009, and 18 in 2010. The majority of victims
      were white males, less than 30-years-old, left a warning note, and were found in
      cars. There were five reports of injuries to first responders, but no secondary
      fatalities. CONCLUSION: H(2)S suicides are increasing in the U.S., and their
      incidence is probably underestimated by public health officials and physicians.
      First responders are at risk when assessing these victims due to the severe
      toxicity of the gas. Emergency providers must be aware of H(2)S suicides to
      educate others and care for the rare survivor.

PMID- 21731787
TI  - Pre-Teen Alcohol Use as a Risk Factor for Victimization and Perpetration of
      Bullying among Middle and High School Students in Georgia.
AB  - OBJECTIVE: We examined the association between pre-teen alcohol use initiation
      and the victimization and perpetration of bullying among middle and high school
      students in Georgia. METHODS: We computed analyses using data from the 2006
      Georgia Student Health Survey (N=175,311) of students in grades 6, 8, 10 and 12.
      The current analyses were limited to students in grades 8, 10 and 12 (n=122,434).
      We used multilogistic regression analyses to determine the associations between
      early alcohol use and reports of both victimization and perpetration of bullying,
      perpetration only, victimization only, and neither victimization or perpetration,
      while controlling for demographic characteristics, other substance use, peer
      drinking and weapon carrying. RESULTS: Pre-teen alcohol use initiation was
      significantly associated with both bullying perpetration and victimization
      relative to non drinkers in bivariate analyses (OR=3.20 95%CI:3.03-3.39). The
      association was also significant between pre-teen alcohol use initiation and
      perpetration and victimization of bullying in analyses adjusted for confounders
      (Adj.OR=1.74; 95%CI:1.61-1.89). Overall, findings were similar for boys and
      girls. CONCLUSION: Pre-teen alcohol use initiation is an important risk factor
      for both the perpetration and victimization of bullying among boys and girls in
      Georgia. Increased efforts to delay and reduce early alcohol use through clinical
      interventions, education and policies may also positively impact other health
      risk behaviors, including bullying.

PMID- 21731788
TI  - Associations between Electronic Media Use and Involvement in Violence, Alcohol
      and Drug Use among United States High School Students.
AB  - OBJECTIVE: We identified associations between time spent watching television and
      time spent playing video or computer games or using computers and involvement in
      interpersonal violence, alcohol and drug use in a nationally representative
      sample of United States high school students. METHODS: We analyzed data from the
      2007 national Youth Risk Behavior Survey. Exposure variables were time spent
      watching television and time spent playing computer or video games or using
      computers (hereafter denoted as "computer/video game use") on an average school
      day; outcome variables included multiple measures assessing involvement in
      violence and alcohol or drug use. Chi-square tests were used to identify
      statistically significant associations between each exposure variable and each of
      the outcome variables. We used logistic regression to obtain crude odds ratios
      for outcome variables with a significant chi-square p-value and to obtain
      adjusted odds ratios controlling for sex, race, and grade in school. RESULTS:
      Overall, 35.4% (95% CI=33.1%-37.7%) of students reported frequent television (TV)
      use and 24.9% (95% CI=22.9%-27.0%) reported frequent computer/video game use. A
      number of risk behaviors, including involvement in physical fights and initiation
      of alcohol use before age 13, were significantly associated with frequent TV use
      or frequent computer/video game use, even after controlling for sex,
      race/ethnicity and grade. CONCLUSION: Findings highlight the need for additional
      research to better understand the mechanisms by which electronic media exposure
      and health-risk behaviors are associated and for the development of strategies
      that seek to understand how the content and context (e.g., watching with peers,
      having computer in common area) of media use influence risk behaviors among
      youth.

PMID- 21731789
TI  - A case study with an identified bully: policy and practice implications.
AB  - OBJECTIVE: Bullying is a serious public health problem that may include verbal or
      physical injury as well as social isolation or exclusion. As a result, research
      is needed to establish a database for policies and interventions designed to
      prevent bullying and its negative effects. This paper presents a case study that
      contributes to the literature by describing an intervention for bullies that has
      implications for practice and related policies regarding bullying. METHODS: An
      individualized intervention for an identified bully was implemented using the
      Participatory Culture-Specific Intervention Model (PCSIM; Nastasi, Moore, &
      Varjas, 2004) with a seventh-grade middle school student. Ecological and culture
      specific perspectives were used to develop and implement the intervention that
      included psychoeducational sessions with the student and consultation with the
      parent and school personnel. A mixed methods intervention design was used with
      the following informants: the target student, the mother of the student, a
      teacher and the school counselor. Qualitative data included semi-structured
      interviews with the parent, teacher and student, narrative classroom observations
      and evaluation/feedback forms filled out by the student and interventionist.
      Quantitative data included the following quantitative surveys (i.e., Child Self
      Report Post Traumatic Stress Reaction Index and the Behavior Assessment Scale for
      Children). Both qualitative and quantitative data were used to evaluate the
      acceptability, integrity and efficacy of this intervention. RESULTS: The process
      of intervention design, implementation and evaluation are described through an
      illustrative case study. Qualitative and quantitative findings indicated a
      decrease in internalizing, externalizing and bullying behaviors as reported by
      the teacher and the mother, and a high degree of acceptability and treatment
      integrity as reported by multiple stakeholders. CONCLUSION: This case study makes
      important contributions by describing an intervention that is targeted to
      specific needs of the bully by designing culture specific interventions and
      working with the student's unique environmental contexts. Contributions also are
      made by illustrating the use of mixed methods to document acceptability,
      integrity and efficacy of an intervention with documented positive effects in
      these areas. In addition, implications for policy and practice related to the
      treatment of students identified as bullies and future research needs are
      discussed.

PMID- 21731790
TI  - Dyadic Characteristics and Intimate Partner Violence among Men Who Have Sex with
      Men.
AB  - OBJECTIVE: Although the research community has begun to recognize intimate
      partner violence (IPV) as an important issue in same-sex relationships, there has
      been a lack of attention to characteristics of these relationships that may be
      associated with IPV. In particular, there has been a lack of attention paid to
      the associations between dyadic characteristics and IPV in same-sex
      relationships. This paper examined associations between dyadic characteristics,
      including relationship satisfaction, communal coping and efficacy, and
      perpetrating and experiencing IPV among a sample of United States men who have
      sex with men (MSM). METHODS: We collected data via an online survey with 528 MSM,
      who were greater than 18 years of age and reported at least one male sex partner
      in the last 12 months. The analysis examined dyadic factors associated with
      reporting of experiencing and perpetrating emotional violence, physical violence,
      and sexual violence. RESULTS: The prevalence of violence in the sample ranged
      from nine percent reporting perpetrating sexual violence to 33% of men reporting
      experiencing emotional violence. MSM who reported greater satisfaction with their
      relationship or who reported a higher degree of concordance with their partner on
      lifestyle choices were less likely to report experiencing or perpetrating
      emotional violence. MSM who perceived a stigma to being in a male same-sex couple
      were less likely to report experiencing or perpetrating sexual violence.
      CONCLUSION: The results presented here demonstrate high levels of IPV among MSM
      and that dyadic characteristics are associated with the occurrence of IPV.
      Understanding relationship characteristics associated with increased IPV among
      same-sex male couples can contribute to the development of more accurate IPV
      screening tools, and more sensitively and appropriately designed intervention
      messages.

PMID- 21731791
TI  - Rape victimization and high risk sexual behaviors: longitudinal study of african
      american adolescent females.
AB  - OBJECTIVES: African-American women are affected by disproportionately high rates
      of violence and sexually transmitted infections (STI)/human immunodeficiency
      virus (HIV) infection. It is imperative to address the intersection of these two
      urgent public health issues, particularly as these affect African-American
      adolescent girls. This study assessed the prevalence of rape victimization (RV)
      among a sample of African-American adolescent females and examined the extent to
      which participants with a history of RV engage in STI/HIV associated risk
      behaviors over a 12-month time period. METHODS: Three hundred sixty-seven African
      American adolescent females ages 15-21, seeking sexual health services at three
      local teenager-oriented community health agencies in an urban area of the
      Southeastern United States, participated in this study. Participants were asked
      to complete an audio computer-assisted self-interview (ACASI) at baseline, 6- and
      12-month follow-up. We assessed sociodemographics, history of RV and sexual
      practices. At baseline, participants indicating they had experienced forced sex
      were classified as having a history of RV. RESULTS: Twenty-five percent of
      participants reported a history of RV at baseline. At 6- and 12-months, victims
      of RV had significantly lower proportions of condom-protected sex (p=.008),
      higher frequency of sex while intoxicated (p=.005), more inconsistent condom use
      (p=.008), less condom use at last sex (p=.017), and more sex partners (p=.0001)
      than non-RV victims. Over the 12-month follow-up period, of those who did not
      report RV at baseline, 9.5% reported that they too had experienced RV at some
      point during the 12-month time frame. CONCLUSION: African-American adolescent
      females who experience RV are engaging in more risky sexual behaviors over time
      than non-RV girls, thereby placing themselves at higher risk for contracting
      STIs. In light of the results from this unique longitudinal study, we discuss
      considerations for policies and guidelines targeting healthcare, law enforcement
      and educational and community settings. The complexities of RV screening in
      healthcare settings are examined as is the need for tighter collaboration between
      healthcare providers and law enforcement. Finally, we consider the role of
      prevention and intervention programs in increasing awareness about RV as well as
      serving as an additional safe environment for screening and referral.

PMID- 21731792
TI  - Intimate Partner Violence and Sexual Risk-taking among Men Who Have Sex with Men
      in South Africa.
AB  - OBJECTIVE: A growing body of literature suggests that men who have sex with men
      (MSM) represent a high risk group for human immunodeficiency virus (HIV)
      infection in Africa, but are often overlooked in the development of HIV
      interventions and programming. Little attention has been paid to the presence of
      intimate partner violence (IPV) among MSM in African settings. This paper
      examines reporting of IPV among a sample of predominantly white, gay internet
      recruited MSM in South Africa and examines associations between IPV and sexual
      risk-taking. METHODS: Internet-using MSM were recruited through selective
      placement of banner advertisements on Facebook.com. Eligibility criteria were
      over 18-years-old, residence in South Africa and self-reporting of recent male
      male sexual behavior. There were 777 eligible respondents, of which 521 MSM with
      complete data are included in the final analysis. Ninety percent of the sample
      reported a White/ European race, and 96% self-identified as gay. RESULTS: The
      prevalence of IPV, both experienced and perpetrated, was relatively high, with 8%
      of men reporting having experienced recent physical IPV and 4.5% of men reporting
      recent experiences of sexual IPV. Approximately 4.5% of MSM reported recently
      perpetrating physical IPV, while the reporting of perpetration of recent sexual
      IPV was much lower at 0.45%. Reporting of experiencing and perpetration of
      physical IPV was significantly associated with race, level of education and
      reporting recent unprotected anal sex. Reporting of experiencing recent sexual
      IPV was significantly associated with reported experiences of homophobia.
      CONCLUSION: There is a limited amount of data on IPV within same-sex
      relationships in South Africa, and the results presented here suggest that the
      prevalence of IPV within this White/European and gay population is cause for
      concern. Collection of IPV data through surveys administered via social
      networking sites is feasible and represents a way of reaching otherwise
      marginalized population groups in IPV research; although in this instance Black
      Africans and MSM who did not identify as gay were severely under-represented.

PMID- 21731793
TI  - Treatment, Services and Follow-up for Victims of Family Violence in Health
      Clinics in Maputo, Mozambique.
AB  - BACKGROUND: Family violence (FV) is a global health problem that not only impacts
      the victim, but the family unit, local community and society at large. OBJECTIVE:
      To quantitatively and qualitatively evaluate the treatment and follow up provided
      to victims of violence amongst immediate and extended family units who presented
      to three health centers in Mozambique for care following violence. METHODS: We
      conducted a verbally-administered survey to self-disclosed victims of FV who
      presented to one of three health units, each at a different level of service, in
      Mozambique for treatment of their injuries. Data were entered into SPSS (SPSS,
      version 13.0) and analyzed for frequencies. Qualitative short answer data were
      transcribed during the interview, coded and analyzed prior to translation by the
      principal investigator. RESULTS: One thousand two hundred and six assault victims
      presented for care during the eight-week study period, of which 216 disclosed the
      relationship of the assailant, including 92 who were victims of FV. Almost all
      patients (90%) waited less than one hour to be seen, with most patients (67%)
      waiting less than 30 minutes. Most patients did not require laboratory or
      radiographic diagnostics at the primary (70%) and secondary (93%) health
      facilities, while 44% of patients received a radiograph at the tertiary care
      center. Among all three hospitals, only 10% were transferred to a higher level of
      care, 14% were not given any form of follow up or referral information, while 13%
      required a specialist evaluation. No victims were referred for psychological
      follow-up or support. Qualitative data revealed that some patients did not
      disclose violence as the etiology, because they believed the physician was unable
      to address or treat the violence-related issues and/or had limited time to
      discuss. CONCLUSION: Healthcare services for treating the physical injuries of
      victims of FV were timely and rarely required advanced levels of medical care,
      but there were no psychological services or follow-up referrals for violence
      victims. The healthcare environment at all three surveyed health centers in
      Mozambique does not encourage disclosure or self-report of FV. Policies and
      strategies need to be implemented to encourage patient disclosure of FV and
      provide more health system-initiated victim resources.

PMID- 21731794
TI  - Elder financial exploitation: implications for future policy and research in
      elder mistreatment.
AB  - Recent advances in the understanding of elder mistreatment have demonstrated that
      financial exploitation tends to be one of the most common forms of mistreatment
      affecting older populations. Agencies such as the World Bank and World Health
      Organization show significant concern regarding financial exploitation and its
      connection to physical and emotional injury to victims. The World Bank uses the
      term "financial violence" as a means of generally describing the harm caused to
      an individual as a result of financial exploitation or abuse. The proportion of
      financial exploitation in relation to other forms of elder mistreatment is
      defined in our research. We discuss the potential impact of elder financial
      exploitation on victims as well as explore the implications for future research
      and policy development focused on financial aspects of elder mistreatment and
      call for further study in the concept of financial exploitation as a violent act.

PMID- 21731795
TI  - A survey of georgia adult protective service staff: implications for older adult
      injury prevention and policy.
AB  - BACKGROUND: The aging population is a rapidly growing demographic. Isolation and
      limited autonomy render many of the elderly vulnerable to abuse, neglect and
      exploitation. As the population grows, so does the need for Adult Protective
      Services (APS). This study was conducted to examine current knowledge of older
      adult protection laws in Georgia among APS staff and to identify training
      opportunities to better prepare the APS workforce in case detection and
      intervention. METHODS: The Georgia State University Institute of Public Health
      faculty developed a primary survey in partnership with the Georgia Division of
      Aging Services' leadership to identify key training priority issues for APS
      caseworkers and investigators. A 47-item electronic questionnaire was delivered
      to all APS employees via work-issued email accounts. We conducted descriptive
      analyses, t-tests and chi-square analyses to determine APS employees' baseline
      knowledge of Georgia's elder abuse policies, laws and practices, as well as
      examine associations of age, ethnicity, and educational attainment with
      knowledge. We used a p-value of 0.05 and 95% confidence intervals to determine
      statistical significance of analyses performed. RESULT: Ninety-two out of 175 APS
      staff responded to the survey (53% response rate). The majority of respondents
      were Caucasian (56%) women (92%). For over half the survey items, paired sample t
      tests revealed significant differences between what APS staff reported as known
      and what APS staff members indicated they needed to know more about in terms of
      elder abuse and current policies. Chi-square tests revealed that non-Caucasians
      significantly preferred video conferencing as a training format (44% compared to
      18%), [chi(2)(1) = 7.102, p < .008], whereas Caucasians preferred asynchronous
      online learning formats (55% compared to 28%) [chi(2)(1) =5.951, p < .015].
      CONCLUSION: Results from this study provide the Georgia Division of Aging with
      insight into specific policy areas that are not well understood by APS staff.
      Soliciting input from intended trainees allows public health educators to tailor
      and improve training sessions. Trainee input may result in optimization of policy
      implementation, which may result in greater injury prevention and protection of
      older adults vulnerable to abuse, neglect and exploitation.

PMID- 21731796
TI  - Sanctification of Parenting, Moral Socialization, and Young Children's Conscience
      Development.
AB  - Religion is important to most U.S. families, but is often overlooked in research
      on children's development. This study examined parental religious beliefs about
      the sanctification of parenting, parental disciplinary strategies, and the
      development of young children's conscience in a sample of 58 two-parent families
      with a preschool child. Fathers were more punitive and used less induction when
      disciplining their children than did mothers. Maternal and paternal reports of
      the sanctification of parenting were positively related to positive
      socialization/praise and the use of induction. When mothers and fathers in the
      family were both using induction, children had higher scores on moral conduct.
      Parents' use of positive socialization combined with a belief in the
      sanctification of parenting predicted children's conscience development.

PMID- 21731797
TI  - Victim-Offender Relationship Status Moderates the Relationships of Peritraumatic
      Emotional Responses, Active Resistance, and Posttraumatic Stress Symptomatology
      in Female Rape Survivors.
AB  - This study examined whether the level of victim-offender relationship (VOR)
      moderated the relationship between peritraumatic fear and active resistance as
      well as the relationship between peritraumatic fear and posttraumatic stress
      symptom severity in a community sample of female rape survivors. One hundred
      thirty-five participants were interviewed about their emotional and behavioral
      responses during the rape and assessed for posttraumatic stress symptomatology
      within one month of the assault. Results indicated that peritraumatic fear was
      positively associated with active resistance, but only among survivors of
      acquaintance rape. Additionally, peritraumatic fear was positively associated
      with posttraumatic stress symptom severity, but only among survivors of intimate
      partner rape. These results suggest that VOR may be an important contextual
      factor that influences emotional and behavioral responses during rape as well as
      posttraumatic stress symptomatology in its aftermath.

PMID- 21731798
TI  - Highly Sensitive Vibrational Imaging by Femtosecond Pulse Stimulated Raman Loss.
AB  - Nonlinear vibrational imaging of live cells and organisms is demonstrated by
      detecting femtosecond pulse stimulated Raman loss. Femtosecond pulse excitation
      produced a 12 times larger stimulated Raman loss signal than picosecond pulse
      excitation. The large signal allowed real-time imaging of the conversion of
      deuterated palmitic acid into lipid droplets inside live cells, and three
      dimensional sectioning of fat storage in live C. elegans. With the majority of
      the excitation power contributed by the Stokes beam in the 1.0 to 1.2 MUm
      wavelength range, photodamage of biological samples was not observed.

PMID- 21731799
TI  - Two-photon microscopy for chemical neuroscience.
AB  - Microscopes using non-linear excitation of chromophores with pulsed near-IR light
      can generate highly localized foci of molecules in the electronic singlet state
      that are concentrated in volumes of less than one femtoliter. The three
      dimensional confinement of excitation arises from the simultaneous absorption of
      two IR photons of approximately half the energy required for linear excitation.
      Two-photon microscopy is especially useful for two types of interrogation of
      neural processes. First, uncaging of signaling molecules such as glutamate, as
      stimulation is so refined it can be used to mimic normal unitary synaptic levels.
      In addition, uncaging allows complete control of the timing and position of
      stimulation, so the two-photon light beam provides the chemical neuroscientist
      with an "optical conductor's baton" which can command synaptic activity at will.
      A second powerful feature of two-photon microscopy is that when used for
      fluorescence imaging it enables the visualization of cellular structure and
      function in living animals at depths far beyond that possible with normal
      confocal microscopes. In this review I provide a survey of the many important
      applications of two-photon microscopy in these two fields of neuroscience, and
      suggest some areas for future technical development.

PMID- 21731800
TI  - Benzothiophene Selective Estrogen Receptor Modulators Provide Neuroprotection by
      a novel GPR30-dependent Mechanism.
AB  - The clinical benzothiophene SERM (BT-SERM), raloxifene, was compared with
      estrogens in protection of primary rat neurons against oxygen-glucose deprivation
      (OGD). Structure-activity relationships for neuroprotection were determined for a
      family of BT-SERMs displaying a spectrum of ERalpha and ERbeta binding affinity
      and agonist/antagonist activity, leading to discovery of a neuroprotective
      pharmacophore, present in the clinically relevant SERMS, raloxifene and
      desmethylarzoxifene (DMA), for which submicromolar potency was observed for
      neuroprotection. BT-SERM neuroprotection did not correlate with binding to ER nor
      classical ER activity, however, both the neuroprotective SERMs and estrogens were
      shown, using pharmacological probes, to activate the same kinase signaling
      cascades. The antiestrogen ICI 182,780 inhibited the actions of estrogens, but
      not those of BT-SERMs, whereas antagonism of the G-protein coupled receptor,
      GPR30, was effective for both SERMs and estrogens. Since SERMs have antioxidant
      activity, ER-independent mechanisms were studied using the classical phenolic
      antioxidants, BHT and Trolox, and the Nrf2-dependent cytoprotective electrophile,
      sulforaphane. However, neuroprotection by these agents was not sensitive to GPR30
      antagonism. Collectively, these data indicate that the activity of
      neuroprotective BT-SERMs is GPR30-dependent and ER-independent and not mediated
      by antioxidant effects. Comparison of novel BT-SERM derivatives and analogs
      identified a neuroprotective pharmacophore of potential use in design of novel
      neuroprotective agents with a spectrum of ER activity.

PMID- 21731801
TI  - Smoking effect on ischemic heart disease in young patients.
AB  - OBJECTIVE: To evaluate the effect of tobacco smoking on the risk of nonfatal
      acute myocardial infarction in young adults (<=45 years). PATIENT AND METHODS: We
      conducted a population-based case-control study with 329 incident acute
      myocardial infarction cases (42 women; 287 men), consecutively admitted to the
      Cardiology department of hospitals in Aleppo, Syria, and 778 controls (486 women;
      292 men), selected within the noninstitutionalized Aleppo population, during 2008
      2010. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using
      unconditional logistic regression. RESULTS: The prevalence of current smoking was
      80.8% in male cases and 53.8% in male controls (OR = 3.63, 95%CI: 2.50, 5.27) and
      59.5% of female cases were smokers compared with 35.8% of controls (OR = 2.64,
      95%CI: 1.39, 5.02). No interaction was found between current smoking and gender
      on myocardial infarction risk (P = 0.401). A dose-effect response was present,
      the odds favoring myocardial infarction reaching an eight-fold increase for those
      who smoked >25 cigarettes/day compared with never smokers. The risk estimate for
      former smokers was similar to never smokers. CONCLUSIONS: Tobacco smoking is an
      important independent risk factor for acute myocardial infarction in young
      adults, with similar strength of association for both genders.

PMID- 21731802
TI  - Coronary Artery Disease in Patients Aged 35 or less - A Different Beast?
AB  - AIM: To assess the extent and severity of coronary artery disease (CAD) in 200
      consecutive patients aged 35 years or less undergoing diagnostic coronary
      angiography. PATIENTS AND METHODS: Findings in these 200 patients (<= 35 years of
      age) were analyzed to find the extent and severity of CAD. The mean age was 31.69
      (+/-3.76) years. Majority were males (94%) and from the Arab ethnicity (70.5%).
      RESULT: Smoking (71%) and history of premature CAD (27%) were the most frequent
      risk factors (RF). History of previous ST elevation myocardial infarction (MI)
      was present in 68%. Anterior wall MI was the most frequent location (63.3%). The
      majority (54.3%) had moderate or large size MI. Ejection fraction (EF) less than
      50% was noted in 30.3%. Left main or triple vessel CAD was seen in 15%. One- and
      two-vessel CAD was seen in 32.5% and 19% patients, respectively. Coronary
      angiogram was completely normal in 23.5%. The majority (54.5%) were treated
      conservatively and the rest (45.5%) needed percutaneous coronary intervention
      (PCI) or coronary artery bypass graft (CABG). The mean number of stents used was
      1.3 +/- 0.67 and the mean length of stents used was 20.3 +/- 12.6 mm. CONCLUSION:
      The extent and severity of CAD was very significant in this subgroup of very
      young (<=35 years) Asian patients. Smoking was the main risk factor and half of
      the patients needed either PCI or CABG.

PMID- 21731803
TI  - Relationship between admitting nonfasting blood glucose and in-hospital mortality
      stratified by diabetes mellitus among acute coronary syndrome patients in oman.
AB  - BACKGROUND AND OBJECTIVES: Hyperglycemia in patients admitted for acute coronary
      syndrome (ACS) is associated with increased in-hospital mortality. We evaluated
      the relationship between admitting (nonfasting) blood glucose and in-hospital
      mortality in patients with and without diabetes mellitus (DM) presenting with ACS
      in Oman. PATIENTS AND METHODS: Data were analyzed from 1551 consecutive patients
      admitted to 15 hospitals throughout Oman, with the final diagnosis of ACS during
      May 8, 2006 to June 6, 2006 and January 29, 2007 to June 29, 2007, as part of
      Gulf Registry of Acute Coronary Events. Admitting blood glucose was divided into
      four groups, namely, euglycemia (<=7 mmol/l), mild hyperglycemia (>7-<9 mmol/l),
      moderate hyperglycemia (>=9-<11 - mmol/l), and severe hyperglycemia (>=11
      mmol/l). RESULTS: Of all, 38% (n = 584) and 62% (n = 967) of the patients were
      documented with and without a history of DM, respectively. Nondiabetic patients
      with severe hyperglycemia were associated with significantly higher in-hospital
      mortality compared with those with euglycemia (13.1 vs 1.52%; P<0.001), mild
      hyperglycemia (13.1 vs 3.62%; P = 0.003), and even moderate hyperglycemia (13.1
      vs 4.17%; P = 0.034). Even after multivariate adjustment, severe hyperglycemia
      was still associated with higher in-hospital mortality when compared with both
      euglycemia (odds ratio [OR], 6.3; P<0.001) and mild hyperglycemia (OR, 3.43; P =
      0.011). No significant relationship was noted between admitting blood glucose and
      in-hospital mortality among diabetic ACS patients even after multivariable
      adjustment (all P values >0.05). CONCLUSION: Admission hyperglycemia is common in
      ACS patients from Oman and is associated with higher in-hospital mortality among
      those patients with previously unreported DM.

PMID- 21731804
TI  - Effect of gender difference in management of heart failure patients in aseer,
      saudi arabia.
AB  - BACKGROUND: Heart failure (HF) is a common medical problem with a high impact on
      public health. Evidence of gender difference in management of HF is scarce. We
      conducted a retrospective study to evaluate the presence of gender difference in
      management of HF patients admitted to the tertiary care hospital in the Aseer
      region/Saudi Arabia. PATIENTS AND METHODS: A chart review was conducted at Aseer
      Central Hospital (ACH) on consecutive patients admitted with the primary
      diagnosis of HF between Jun 2007 and May 2009. Data were collected on clinical
      and management profiles and analyzed for the presence of gender difference in HF
      management. RESULTS: A total of 206 male patients and 94 female patients with HF
      were reviewed. Ischemic and dilated cardiomyopathy etiologies were significantly
      higher in male patients (42.7 vs. 28.7%, P < 0.021) and (13.1% vs. 3.2%, P <
      0.008), respectively. Renal failure and atrial fibrillation were significantly
      higher in female patients with HF (20.2 vs., 5.3% P < 0.001) and (20.2 vs. 10.2%,
      P < 0.018), respectively. Smoking was significantly higher in male patients (11.7
      vs. 0%, P < 0.001). Echocardiography was performed equally for both genders and
      ejection fraction was significantly higher in female patients (38.2 +/- 16.9% vs.
      30.4 +/- 16.6%, P < 0.001). Beta-blockers were prescribed significantly less to
      female patients (36.2 vs. 57.8%, P < 0.001), while ACE inhibitors and digoxin
      were prescribed significantly less to male patients (64.1 vs.75.5%, P < 0.049)
      and (24.8 vs. 36.2%, P < 0.042), respectively. CONCLUSION: Gender differences
      were detected in clinical presentation and management of HF. Female patients with
      HF had less ischemic etiology and smoking, but more atrial fibrillation and renal
      dysfunction. Female patients were under-treated by Beta-blockers while male
      patients were under-treated by ACE inhibitors and digoxin. Both genders were
      investigated equally, and female patients had a better ejection fraction.

PMID- 21731805
TI  - Very Late Stent Thrombosis of Sirolimus-eluting Stent 59 Months After
      Implantation: A First Report from The Middle-East and Review of Literature.
AB  - Very late stent thrombosis occurs more frequently with drug-eluting stents and
      tends to occur despite dual antiplatelet therapy or after long periods of
      clopidogrel discontinuation. Stent thrombosis commonly presents with myocardial
      infarction or death. We report a 41-year-old Arab male with very late stent
      thrombosis after 59 months of sirolimus-eluting stent implantation and -49 months
      after clopidogrel discontinuation despite aspirin continuation, presenting with
      exertional angina. He underwent successful percutaneous coronary intervention.
      This case underlines the need for novel stent designs as well as newer
      therapeutic strategies in preventing very late stent thrombosis among patients
      receiving drug-eluting stents.

PMID- 21731806
TI  - Successful delivery by a cesarean section in a parturient with severe dilated
      cardiomyopathy, an implantable cardioverter defibrillator, and a repaired
      tetralogy of fallot.
AB  - Repaired congenital heart disease has become more prevalent in women of
      childbearing age. We report an unusual case of a 24-year-old multigravida with a
      repaired tetralogy of Fallot, severe dilated cardiomyopathy, and implantable
      cardioverter defibrillator placement who was managed successfully by a cesarean
      section three times. This case underscores the impact of such events on maternal
      and fetal safety and the importance of a multidisciplinary approach in the
      management of pregnant patients with complex congenital and medical problems.

PMID- 21731807
TI  - Atrioventricular Nodal Re-entrant Tachycardia Ablation: Unusual Function of Slow
      Pathway.
AB  - Slow pathway (SP) ablation is an acceptable, standard method for atrioventricular
      nodal re-entrant tachycardia (AVNRT) ablation. The exact role of SP in the human
      heart and the possible negative implications of SP ablation are unknown. The
      current case report describes an unusual, brief, functional heart block,
      following radiofrequency ablation of the SP. Our findings highlight the peculiar
      property of the SP in maintaining conduction over an atrioventricular (AV) node,
      in circumstances of extreme autonomic imbalance. SP can be ablated without major
      conduction problems for AVNRT. Careful pre-ablation evaluation of the AV
      conduction pattern may assist in predicting occurrences of this type of heart
      block.

PMID- 21731809
TI  - Alternative to animal testing.

PMID- 21731808
TI  - Unusual survival time of primary cardiac sarcoma of the right ventricle.
AB  - Primary cardiac sarcomas are rare tumors with unfavorable prognosis. We report a
      69-year-old male with a right ventricular mass diagnosed as primary malignant
      cardiac sarcoma with unexpected long survival of 16.5 months.

PMID- 21731810
TI  - Tubercular chronic calcific constrictive pericarditis.

PMID- 21731811
TI  - Animal testing and medicine.

PMID- 21731812
TI  - The contribution of animal science to the medical revolution.

PMID- 21731813
TI  - Is network clustering detectable in transmission trees?
AB  - Networks are often used to model the contact processes that allow pathogens to
      spread between hosts but it remains unclear which models best describe these
      networks. One question is whether clustering in networks, roughly defined as the
      propensity for triangles to form, affects the dynamics of disease spread. We
      perform a simulation study to see if there is a signal in epidemic transmission
      trees of clustering. We simulate susceptible-exposed-infectious-removed (SEIR)
      epidemics (with no re-infection) over networks with fixed degree sequences but
      different levels of clustering and compare trees from networks with the same
      degree sequence and different clustering levels. We find that the variation of
      such trees simulated on networks with different levels of clustering is barely
      greater than those simulated on networks with the same level of clustering,
      suggesting that clustering can not be detected in transmission data when re
      infection does not occur.

PMID- 21731814
TI  - A common surgical emergency complicated by anterior spinal cord infarction.

PMID- 21731815
TI  - Valsalva retinopathy in pregnancy. Should we treat?

PMID- 21731816
TI  - Pubic rami and sacral insufficiency fractures resulting in osteomyelitis, vulval
      abscess, discharging bone fragments and pelvic instability.

PMID- 21731817
TI  - Cervical spine tuberculosis causing instability and neurological compromise.

PMID- 21731818
TI  - A randomized questionnaire-based study on the impact of providing numerical
      information on colorectal cancer screening.
AB  - OBJECTIVES: To establish whether the provision of numerical data using pictograms
      and framed as event rates affects subjects' attitudes to colorectal cancer (CRC)
      screening. DESIGN: Randomized questionnaire and telephone study comparing a
      control group given standard NHS CRC information leaflets with an intervention
      group given the same leaflet but enhanced with additional numerical and pictorial
      information. SETTING: District General hospital and two general practices in
      North East England. Study carried out immediately prior to the introduction of
      CRC screening. PARTICIPANTS: A total of 478 non-gastroenterological subjects (age
      range 60-70 years). MAIN OUTCOME MEASURES: The difference in the two groups'
      overall wish to be screened; comparison of the impact of enhanced vs. unenhanced
      summary points in the NHS information leaflet; the summary point that most
      influenced their decision on screening; the views of the intervention group on
      the additional numerical and pictorial information provided. RESULTS: A total of
      256 (54%) responded (124 from the control group and 117 from the intervention
      group); 22% were interviewed by telephone; 90% of the control group and 85% of
      the intervention group wished to be screened (P = 0.34). Provision of numerical
      and pictorial information significantly changed the impact of five of the six
      summary points on the decision to be screened. Sixty-two percent of the
      intervention group found the pictograms helpful while 83% of those interviewed by
      telephone found the numerical data helpful; 73% of the control group when given
      by telephone the additional numerical information given to the intervention group
      said this would have been useful in aiding their decision-making. CONCLUSION:
      Providing additional numerical information would enhance the credibility of the
      screening programme without necessarily reducing the numbers screened.

PMID- 21731819
TI  - Sepsis caused by Raoultella terrigena.

PMID- 21731820
TI  - A rare and unusual case of isolated cerebellar metastasis from a non-muscle
      invasive transitional cell carcinoma of bladder.

PMID- 21731821
TI  - Type II diabetes mellitus: new presentation manifesting as Fournier's gangrene.

PMID- 21731822
TI  - Primary intraosseous osteoblastic meningioma.

PMID- 21731823
TI  - Late-onset capsular bag distension syndrome following cataract surgery.

PMID- 21731824
TI  - Atopic profile of patients failing medical therapy for chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory condition of the
      nasal airway and paranasal sinuses that can broadly be classified into CRS with
      nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The relationship
      between CRS and atopy to inhalant allergens remains unclear. We sought to examine
      the presence of atopy in patients failing medical therapy for both types of CRS.
      The objective of this research was to analyze the frequency and distribution of
      allergen sensitivity in patients failing medical therapy for CRSwNP and CRSsNP in
      comparison to rhinitis patients without CRS and the general population. METHODS:
      A prospectively collected database of 334 consecutive CRS patients who had
      surgery after failing maximal medical therapy was queried to identify those who
      met inclusion criteria: a sinus computed tomography (CT), an endoscopy consistent
      with CRS, and skin-prick testing with 24 common inhalant allergens in 8 classes
      at our institution (n = 125). Additionally, data from these CRS patients were
      compared to a group of 50 patients diagnosed with rhinitis who had similar
      symptoms but radiologically normal CT scans, as well as published normative
      population skin-prick testing data obtained from the National Health and
      Nutrition Examination Study III (NHANES III). The relationship between atopy, as
      assessed by the frequency of skin test positivity, and radiological disease
      severity, was assessed for several allergen classes in CRSwNP, CRSsNP and
      rhinitis patients. RESULTS: One or more positive skin results were observed in
      103 of 125 (82.4%) CRS patients who underwent surgery--a prevalence significantly
      higher than that found in the NHANES III study (p < 0.05) but not different from
      the rhinitis control group (36/50, 72.0%). The most prevalent positive skin test
      results were to dust mites and ragweed in CRSwNP, CRSsNP, and rhinitis patients.
      Comparing these 3 patient groups, there were no significant differences in the
      rates of positive skin-test results to any single allergen. However, the median
      number of skin test-positive results was higher in CRSwNP patients compared to
      CRSsNP and rhinitis patients. Consistent with other studies, we found that CRSwNP
      patients were more likely to be male and have concurrent asthma. CONCLUSION: In
      our series of patients failing medical therapy for CRS, we found higher rates of
      atopy compared with the general population but not compared with rhinitis
      patients. CRSwNP patients with medically refractory sinusitis were more likely to
      have multiple positive skin tests and asthma as compared to the general
      population or patients with either CRSsNP or rhinitis. Host barrier dysfunction
      may play a role in enabling multisensitization.

PMID- 21731825
TI  - Smoking and endoscopic sinus surgery: does smoking volume contribute to clinical
      outcome.
AB  - BACKGROUND: The effect of tobacco smoking on chronic rhinosinusitis (CRS) is not
      yet well-delineated. The purpose of this investigation was to evaluate the
      overall effect of smoking on postoperative outcomes (endoscopic score and health
      related quality-of-life [HRQoL]) after endoscopic sinus surgery (ESS) for CRS and
      to determine if volume of daily smoking impacts outcomes. METHODS: A total of 784
      patients with CRS were prospectively enrolled between January 2001 and April 2009
      after electing ESS from 1 of 3 academic tertiary care centers. Follow-up longer
      than 6 months was available on 39 smoking patients. Smoking volume
      (cigarettes/day) analysis was performed by dichotomizing patients into either of
      2 subgroups: light smokers (<20 cigarettes per day) or heavy smokers (>= 20
      cigarettes per day). Primary outcomes were Lund-Kennedy endoscopy scores and 2
      disease-specific HRQoL instruments: the Rhinosinusitis Disability Index (RSDI)
      and Chronic Sinusitis Survey (CSS). RESULTS: Smokers and nonsmokers experienced
      similar improvement in HRQoL following surgery (RSDI: p = 0.792 and CSS: p =
      0.117). No difference in HRQoL improvements between light smokers and heavy
      smokers was identified. While overall changes in endoscopy scores did not differ
      between smokers and nonsmokers, there was a significant difference in the
      prevalence of worsening postoperative endoscopy scores between heavy smokers,
      light smokers, and nonsmokers (100%, 33%, and 20%, respectively; p = 0.002).
      CONCLUSION: Active smoking status does not alter postoperative improvement in
      HRQoL after ESS. Although limited by a small sample size, increasing smoking
      volume may contribute to worse postoperative endoscopy scores.

PMID- 21731826
TI  - Cytomegalovirus Reactivation in Ulcerative Colitis Patients.
AB  - Ulcerative colitis (UC) patients are believed to have an increased risk for the
      colonic reactivation of cytomegalovirus (CMV) infection due to both inherent and
      iatrogenic factors. Numerous studies and case reports have described CMV
      infection as complicating the disease course of ulcerative colitis patients; the
      existing evidence suggests an association between the presence of CMV infection
      and increased colectomy and mortality rates in UC patients. Whether CMV is
      nonpathogenic with a tropism towards areas of dysplasia and inflammation in the
      colon of UC or plays an active role in pathogenesis is still debated. In this
      paper, we examine the existing evidence for the diagnosis and management of CMV
      infection in UC patients.

PMID- 21731827
TI  - Early Years Policy.
AB  - In this paper, we analyze the role that early years policy might play in
      narrowing educational attainment gaps. We begin by examining gaps in school
      readiness between low-, middle-, and high-income children, drawing on data from
      new large and nationally representative birth cohort studies in the US and UK. We
      find that sizable income-related gaps in school readiness are present in both
      countries before children enter school and then decompose these gaps to identify
      the factors that account for the poorer scores of low-income children. We then
      consider what role early years policy could play in tackling these gaps, drawing
      on the best available evidence to identify promising programs.

PMID- 21731828
TI  - New beginnings.

PMID- 21731829
TI  - Improving quality of depression care using organized systems of care: a review of
      the literature.
AB  - OBJECTIVE: To establish the need for a chronic disease management strategy for
      major depressive disorder (MDD), discuss the challenges involved in implementing
      guideline-level treatment for MDD, and provide examples of successful
      implementation of collaborative care programs. DATA SOURCES: A systematic
      literature search of MEDLINE and the US National Library of Medicine was
      performed. STUDY SELECTION: We reviewed clinical studies evaluating the
      effectiveness of collaborative care interventions for the treatment of depression
      in the primary care setting using the keywords collaborative care, depression,
      and MDD. This review includes 45 articles relevant to MDD and collaborative care
      published through May 2010 and excludes all non-English-language articles.
      RESULTS: Collaborative care interventions include a greater role for nonmedical
      specialists and a supervising psychiatrist with the major goal of improving
      quality of depression care in primary care systems. Collaborative care programs
      restructure clinical practice to include a patient care strategy with specific
      goals and an implementation plan, support for self-management training, sustained
      patient follow-up, and decision support for medication changes. Key components
      associated with the most effective collaborative care programs were improvement
      in antidepressant adherence, use of depression case managers, and regular case
      load supervision by a psychiatrist. Across studies, primary care patients
      randomized to collaborative care interventions experienced enhanced treatment
      outcomes compared with those randomized to usual care, with overall outcome
      differences approaching 30%. CONCLUSIONS: Collaborative care interventions may
      help to achieve successful, guideline-level treatment outcomes for primary care
      patients with MDD. Potential benefits of collaborative care strategies include
      reduced financial burden of illness, increased treatment adherence, and long-term
      improvement in depression symptoms and functional outcomes.

PMID- 21731830
TI  - Patient health questionnaire depression scale as a suicide screening instrument
      in depressed primary care patients: a cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to examine the sensitivity and specificity
      of the suicide item on the 9-item Patient Health Questionnaire (PHQ-9) when
      compared to a structured interview (the Structured Clinical Interview for DSM-IV;
      SCID-I mood module) in primary care patients with elevated depression symptoms.
      METHOD: In this cross-sectional study, we analyzed data from 166 patients from 2
      primary care clinics, 1 in Rhode Island and 1 in Massachusetts, who were enrolled
      in studies that focused on depression in primary care. Of the total participants,
      101 were enrolled in the survey study, and 65 were screened for or enrolled in
      either an open trial or a pilot randomized controlled trial. Data were collected
      between May 2004 and May 2009. RESULTS: We found that the specificity of the PHQ
      9 suicide screening item was 0.84 and sensitivity was 0.69 for the sample as a
      whole. CONCLUSIONS: This study suggests that the routine use of the PHQ-9 may be
      useful in primary care practice in that it may identify individuals at risk for
      suicide who would not otherwise have been identified. However, denial of
      suicidality on the PHQ-9 should be probed further if there are other risk factors
      for suicide present. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00541957.

PMID- 21731831
TI  - Safety and tolerability of aripiprazole in the treatment of irritability
      associated with autistic disorder in pediatric subjects (6-17 years old):results
      from a pooled analysis of 2 studies.
AB  - BACKGROUND: With increasing use of atypical antipsychotics among pediatric
      patients, detailed information about safety and tolerability is crucial. METHOD:
      Data were pooled from two 8-week, randomized, double-blind, multicenter, parallel
      group trials comparing aripiprazole versus placebo in subjects aged 6 to 17 years
      with irritability associated with DSM-IV-TR-diagnosed autistic disorder: one
      flexibly dosed (aripiprazole 2-15 mg/d; target of 5, 10, or 15 mg/d), the other
      fixed-dose (aripiprazole 5, 10, or 15 mg/d). The first was conducted from June
      2006-April 2008, and the second, from June 2006-June 2008. Adverse events were
      characterized with respect to incidence, duration, severity, timing of peak
      incidence of onset, and dose-response relationship. Extrapyramidal symptoms,
      drooling, and metabolic parameters were evaluated. RESULTS: Three hundred
      thirteen subjects comprised the safety sample (aripiprazole 212, placebo 101).
      Discontinuations due to adverse events with aripiprazole versus placebo were,
      overall, 10.4% versus 6.9%; subjects 6-12 years: 10.8% versus 5.1%; and subjects
      13-17 years: 8.9% versus 13.6%. Common adverse events with aripiprazole versus
      placebo included sedation (20.8% vs 4.0%), fatigue (16.5% vs 2.0%), vomiting
      (13.7% vs 6.9%), increased appetite (12.7% vs 6.9%), somnolence (10.4% vs 4.0%),
      and tremor (9.9% vs 0.0%). Most adverse events were mild or moderate and occurred
      early. Only fatigue showed a dose-response relationship (P < .05). Mean body
      weight change (last observation carried forward, 1.6 vs 0.4 kg) was higher with
      aripiprazole than placebo (P < .001). There were no between-treatment differences
      in metabolic changes. The extrapyramidal symptom-related adverse event incidence
      with aripiprazole versus placebo was, overall, 20.8% vs 9.9%; the incidence of
      akathisia-related events was 3.3% vs 8.9%. CONCLUSIONS: Aripiprazole was
      generally safe and well tolerated in subjects (6-17 years) with irritability
      associated with autistic disorder in these 8-week studies; clinicians should be
      aware of this clinical profile and strategies to manage adverse events if they
      occur. TRIAL REGISTRATION: clinicaltrials.gov Identifiers NCT00332241 and
      NCT00337571.

PMID- 21731832
TI  - Failure to fill electronically prescribed antidepressant medications: a
      retrospective study.
AB  - OBJECTIVE: Nonadherence to antidepressants has been reported to range widely from
      10% to 60%. Most adherence studies focus on persistence of use and do not include
      prescriptions that are not picked up by the patient. The objectives of this study
      were to determine the rate of unfilled antidepressant prescriptions as well as to
      identify factors associated with failure to fill these prescriptions. METHOD:
      This retrospective study used administrative and pharmacy data from a mid
      Atlantic managed care organization serving 3.3 million medical members and 1.2
      million pharmacy members. Electronic prescriptions for citalopram, duloxetine,
      sertraline, and venlafaxine sent to pharmacies from July 1, 2007, to June 30,
      2009, were matched to pharmacy claims to determine the rate of unfilled
      antidepressant prescriptions. Patients were >=18 years of age and had continuous
      pharmacy coverage from July 1, 2006, to July 31, 2009. Logistic regression was
      used to assess whether clinical and demographic factors were associated with
      unfilled electronic prescriptions. RESULTS: There were 557 electronically
      prescribed antidepressants for 267 patients. The rate of unfilled electronic
      prescriptions was 13.1%, which affected 19.9% of patients. Electronic
      prescriptions for new users of the antidepressant were 5 times more likely to be
      unfilled (odds ratio [OR]=5.13; 95% CI, 2.66-9.91; P<.001) than those for
      previous users. Antidepressant prescriptions for patients aged 18-34 years were
      most likely to be unfilled (OR=3.72; 95% CI, 1.81-7.67; P<.001). CONCLUSIONS:
      Nonadherence to antidepressants is a significant problem with one-fifth of
      patients never receiving their electronically prescribed antidepressant.
      Prescriptions for patients without a previous antidepressant claim and aged 18-34
      years were least likely to be filled. Interventions targeting patients who fail
      to fill their antidepressant prescription are needed.

PMID- 21731833
TI  - Effects of adjunctive aripiprazole on sexual functioning in patients with major
      depressive disorder and an inadequate response to standard antidepressant
      monotherapy: a post hoc analysis of 3 randomized, double-blind, placebo
      controlled studies.
AB  - OBJECTIVE: To investigate the specific effect of adjunctive aripiprazole on
      sexual function in patients with major depressive disorder and a history of an
      inadequate response to antidepressant medication by controlling for improvement
      in depressive symptoms as measured by improvement in Montgomery-Asberg Depression
      Rating Scale (MADRS) total scores. METHOD: For this post hoc analysis, data were
      pooled from 3 multicenter, randomized, double-blind, placebo-controlled
      aripiprazole augmentation studies (CN138-139: June 2004-April 2006; CN138-163:
      September 2004-December 2006; and CN138-165: March 2005-April 2008). Outpatients
      who met DSM-IV-TR criteria for a major depressive episode that had lasted >=8
      weeks with an inadequate response to prospective antidepressant treatment were
      randomized to adjunctive aripiprazole or placebo for 6 weeks. Sexual functioning
      was assessed using the Massachusetts General Hospital Sexual Functioning
      Inventory (MGH-SFI). To assess whether adjunctive aripiprazole improves sexual
      functioning directly, rather than as an indirect effect of improvement in
      depression symptoms, the mean change in MGH-SFI item scores and overall
      improvement scores was assessed using analysis of covariance, with double-blind
      baseline and change in MADRS total score as covariates. Correlations between MGH
      SFI items and MADRS total score and prolactin levels were also assessed. RESULTS:
      The analysis included 1,092 subjects (n=737 female and n=355 male). In the total
      population, adjunctive aripiprazole demonstrated statistically significant
      greater improvements versus placebo on the MGH-SFI item "interest in sex" (-0.34
      vs -0.18, P<.05). In males, no significant treatment differences were observed.
      In females, improvements in sexual functioning with adjunctive aripiprazole
      versus placebo were found on the MGH-SFI items "interest in sex" (-0.41 vs -0.21,
      P<.05) and "sexual satisfaction" (-0.44 vs -0.25, P<.05). CONCLUSIONS:
      Aripiprazole adjunctive to antidepressant treatment can have some beneficial
      effects on sexual functioning in patients with major depressive disorder who
      respond inadequately to standard antidepressant treatment; the benefits in women
      were specific to sexual interest and satisfaction and were independent of the
      improvement in depressive symptoms. TRIAL REGISTRATION: clinicaltrials.gov
      Identifiers: NCT00095823, NCT00095758, and NCT00105196.

PMID- 21731834
TI  - Patients with borderline personality disorder and major depressive disorder are
      not distinguishable by their neuropsychological performance: a case-control
      study.
AB  - OBJECTIVE: Patients with borderline personality disorder (BPD) and patients with
      major depressive disorder (MDD) exhibit a broad range of neuropsychological
      deficits. Studies in both groups of patients point to differences but also
      similarities. However, studies that compare both patient groups are missing from
      the literature. The present study aimed to compare neuropsychological functioning
      in BPD and MDD patients. METHOD: Eighteen patients with BPD, 27 patients with
      MDD, 17 patients with BPD and MDD, and 76 healthy control subjects were included
      in the case-control study. Patients were treated for their disorders as
      inpatients of the Clinic of Psychiatry and Psychotherapy Bethel, Ev. Hospital
      Bielefeld (Bielefeld, Germany). All patients met DSM-IV diagnoses as assessed by
      trained psychotherapists within the first week of their admission. In addition to
      a comprehensive neuropsychological test battery, the inhibitory control of
      emotional stimuli was assessed. Data were collected between June 2004 and June
      2007. RESULTS: Patients showed only a few impairments and no increased
      distractibility toward emotionally negative stimuli. Patients with BPD and
      patients with MDD were not distinguishable by the neuropsychological test
      results. CONCLUSIONS: These data did not support the notion of specific
      neuropsychological profiles in BPD and MDD. Future research needs to clarify the
      overlap of symptoms between both disorders.

PMID- 21731835
TI  - Remission with venlafaxine extended release or selective serotonin reuptake
      inhibitors in depressed patients: a randomized, open-label study.
AB  - BACKGROUND: This randomized, open-label, rater-blinded, multicenter study
      compared treatment outcomes with the serotonin-norepinephrine reuptake inhibitor
      (SNRI) venlafaxine extended release (ER) with selective serotonin reuptake
      inhibitors (SSRIs) in primary care patients with major depressive disorder.
      METHOD: Study data were collected from November 29, 2000, to March 4, 2003.
      Outpatients who met diagnostic criteria for major depressive disorder according
      to the Mental Health Screener, a computer-administered telephone interview
      program that screens for the most common mental disorders, and had a total score
      on the 17-item Hamilton Depression Rating Scale (HDRS(17)) >= 20 were randomly
      assigned to receive up to 6 months of open-label venlafaxine ER 75-225 mg/d (n =
      688) or an SSRI (n = 697): fluoxetine 20-80 mg/d, paroxetine 20-50 mg/d,
      citalopram 20-40 mg/d, and sertraline 50-200 mg/d. The primary outcome was
      remission (HDRS(17) score <= 7) at study end point using the last-observation
      carried-forward method to account for early termination. A mixed-effects model
      for repeated measures (MMRM) analysis evaluated secondary outcome measures.
      RESULTS: Fifty-one percent of patients completed the study. Month 6 remission
      rates did not differ significantly for venlafaxine ER and the SSRIs (35.5% vs
      32.0%, respectively; P = .195). The MMRM analysis of HDRS(17) scores also did not
      differ significantly (P = .0538). Significant treatment effects favoring the
      venlafaxine ER group were observed for remission rates at days 30, 60, 90, and
      135 and a survival analysis of time to remission (P = .006), as well as Clinical
      Global Impressions-severity of illness scale (P = .0002); Hospital Anxiety and
      Depression Scale-Anxiety subscale (P = .03); 6-item Hamilton Depression Rating
      Scale, Bech version (P = .009); and Quick Inventory of Depressive Symptomatology
      Self-Report (P = .0003). CONCLUSIONS: Remission rates for patients treated with
      venlafaxine ER or an SSRI did not differ significantly after 6 months of
      treatment. Results of most secondary analyses suggested that SNRI treatment had a
      greater antidepressant effect versus the SSRIs studied.

PMID- 21731836
TI  - A case of hypomania induced by lamotrigine augmentation.

PMID- 21731837
TI  - Efficacy of duloxetine and agomelatine does not exceed that of other
      antidepressants in patients with autistic disorder: preliminary results in 3
      patients.

PMID- 21731838
TI  - Lamotrigine-induced manic switch: a report of 2 cases.

PMID- 21731839
TI  - Two case reports of confusion psychosis: should we reevaluate the place of
      cycloid psychoses in modern psychiatry?

PMID- 21731840
TI  - Aripiprazole in treating a manic episode associated with hydrocephalus: a case
      report.

PMID- 21731841
TI  - The relationship between suicide attempts and borderline personality in gastric
      surgery candidates.

PMID- 21731842
TI  - A case of relapsing priapism associated with long-acting injectable risperidone.

PMID- 21731843
TI  - Recurrent catatonia treated with lithium and carbamazepine: a series of 2 cases.

PMID- 21731844
TI  - Atypical antipsychotics and insulin resistance in acute mental illness: a case
      series.

PMID- 21731845
TI  - Keeping hope alive.

PMID- 21731846
TI  - Prior discharges against medical advice and withdrawal of consent: what they can
      teach us about patient management.

PMID- 21731847
TI  - Acute psychosis and type 2 diabetes mellitus:should screening guidelines be
      revised?
AB  - Although psychosis increases the risk for developing type 2 diabetes, the
      temporal relationship between the onset of psychosis and the onset of diabetes
      has not been studied. We present 6 cases of acute psychosis, which led to the new
      diagnosis of type 2 diabetes during inpatient psychiatric admission within days
      to weeks of the psychotic episode. The implications of these findings and the
      efficacy of current diabetes screening guidelines are discussed.

PMID- 21731848
TI  - Do patients with borderline personality disorder in primary care gain access to
      mental health services?

PMID- 21731849
TI  - Role of the WWOX tumor suppressor gene in bone homeostasis and the pathogenesis
      of osteosarcoma.
AB  - Osteosarcoma is the most common primary bone malignancy in children with unknown
      etiology and often with poor clinical outcome. In recent years, a critical role
      has emerged for the WW domain-containing oxidoreductase (WWOX) in osteosarcoma
      and bone biology. WWOX is a tumor suppressor that is deleted or attenuated in
      most human tumors. Wwox-deficient mice develop osteosarcoma and a bone metabolic
      disease characterized by hypocalcemia and osteopenia. Studies of human
      osteosarcomas have revealed that the WWOX gene is deleted in 30% of cases and
      WWOX protein is absent or reduced in ~60% of tumors. Further, WWOX levels are
      attenuated in the majority of osteosarcoma cells, in which ectopic expression is
      associated with reduced proliferation, migration, invasion and tumorigenicity. At
      the molecular level, WWOX associates with RUNX2 and suppresses its
      transcriptional activity in osteoblasts and in cancer cells. This review provides
      new insights on the current knowledge of the spectrum of WWOX activities and
      future directions for the role of WWOX in bone biology and osteosarcoma.

PMID- 21731850
TI  - Chinese Culture, Homosexuality Stigma, Social Support and Condom Use: A Path
      Analytic Model.
AB  - PURPOSE: The objective of this study was to examine the interrelationships among
      individualism, collectivism, homosexuality-related stigma, social support, and
      condom use among Chinese homosexual men.  METHODS: A cross-sectional study using
      the respondent-driven sampling approach was conducted among 351 participants in
      Shenzhen, China. Path analytic modeling was used to analyze the
      interrelationships.  RESULTS: The results of path analytic modeling document the
      following statistically significant associations with regard to homosexuality:
      (1) higher levels of vertical collectivism were associated with higher levels of
      public stigma [beta (standardized coefficient) = 0.12] and self stigma (beta =
      0.12); (2) higher levels of vertical individualism were associated with higher
      levels self stigma (beta = 0.18); (3) higher levels of horizontal individualism
      were associated with higher levels of public stigma (beta = 0.12); (4) higher
      levels of self stigma were associated with higher levels of social support from
      sexual partners (beta = 0.12); and (5) lower levels of public stigma were
      associated with consistent condom use (beta = -0.19).  CONCLUSIONS: The findings
      enhance our understanding of how individualist and collectivist cultures
      influence the development of homosexuality-related stigma, which in turn may
      affect individuals' decisions to engage in HIV-protective practices and seek
      social support. Accordingly, the development of HIV interventions for homosexual
      men in China should take the characteristics of Chinese culture into
      consideration.

PMID- 21731851
TI  - Changing Knowledge and Attitudes with a Middle School Mental Health Education
      Curriculum.
AB  - PURPOSE: This research tested the effectiveness of a widely used mental health
      education curriculum in changing knowledge and attitudes about mental illness.
      METHOD: Middle school students from four schools were provided the Breaking the
      Silence: Teaching the Next Generation About Mental Illness mental health
      instruction while students from other classes at the same schools received usual
      class instruction. Students completed questionnaires assessing knowledge,
      attitudes, and social distance preferences before, immediately after, and six
      weeks after the instruction was given. RESULTS: Students given the Breaking the
      Silence instruction showed improvements in knowledge about mental illness,
      attitudes toward mental illness, and willingness to interact with people with
      mental illnesses. Students in the comparison classes showed no changes.
      CONCLUSIONS: Breaking the Silence was an effective means of improving the
      knowledge and attitudes of middle school students about mental illness.
      IMPLICATIONS: An easy-to-administer and effective curriculum, Breaking the
      Silence is available to teachers and schools to help improve understanding and
      acceptance of people with mental illness. Such a curriculum, introduced during
      childhood and adolescence, may help to prevent the negative attitudes and
      misunderstanding that characterize adult perceptions of mental illness.

PMID- 21731852
TI  - Quality of independent review board/ethics committee oversight in clinical trials
      in India.

PMID- 21731853
TI  - Comparative effectiveness research.

PMID- 21731854
TI  - Pharmacovigilance for clinical trials in India: Current practice and areas for
      reform.
AB  - Keeping in mind India's increasing participation in multinational trials, this
      article explores potential areas of Indian pharmacovigilance, requiring reform
      and provides recommendations for building a robust safety reporting system.
      Internal discrepancies exist between Schedule Y and Central Drugs Standard
      Control Organisation approval letter regarding what to report. Schedule Y's
      silence on expedited reporting requirements creates confusion for Indian sites
      that are part of multinational trial. Not allowing waiver for serious adverse
      events that are protocol specified or are study endpoints, along with lack of
      emphasis on causality as reporting criteria, adds substantial burden of
      uninformative cases for regulatory review. Despite global focus on Development
      Safety Update Report, Indian regulators are not yet insistent on real-time update
      of a drug's cumulative safety profile. Issues like reporting requirements for
      generic trials, pregnancy reporting and lenient timeline for death/life
      threatening events need attention. Finally, the need to formulate an all
      encompassing pharmacovigilance guideline for India, in sync with global practice
      cannot be overemphasized.

PMID- 21731855
TI  - Strategies for ensuring quality data from Indian investigational sites.
AB  - The topic of ensuring quality and compliance is and must be a top priority in the
      conduct of clinical trials, as warranted by regulatory guidelines as well as the
      inherent responsibility of the professionals conducting such research. Fast
      growing emerging clinical geographies such as India demand special attention due
      to rapid growth and associated factors that may put study quality at risk. In
      this paper, we used the basic principle of PDCA (Plan, Do, Check, and Adjust) to
      structure the processes of a clinical trial from protocol to final analysis in
      order to highlight the interactive nature of involved people and processes
      required to ensure quality of data and site functioning.

PMID- 21731856
TI  - Good documentation practice in clinical research.
AB  - One of the most common inspection findings in investigator site inspections is
      lack of reliable, accurate and adequate source documentation. This also happens
      to be the most common pitfall identified during sponsor audits. The importance of
      good documentation practice needs to be emphasized to investigator sites to
      ensure that the study results are built on the foundation of credible and valid
      data. This article focuses on the key principles of good documentation practice
      and offers suggestions for improvement.

PMID- 21731857
TI  - Trend of clinical drug trials in type 2 diabetes mellitus over last decade.
AB  - BACKGROUND: Type 2 diabetes mellitus (Type 2 DM) has been recognized as the
      recent pandemic; India and China competing each other for the title-"Diabetes
      Capital of the World." A number of new drugs have been recently available and has
      lead to a boom in the clinical drug trial industry. We intend to evaluate the
      trend of clinical drug trials in Type 2 DM over last one decade. MATERIALS AND
      METHODS: Clinical drug trial registry of USA was used for getting the data
      regarding number of drug trials conducted in each country over last decade.
      India, China, and USA being the countries with highest prevalence of diabetes
      were included in the analysis. The percentage share of each country in clinical
      drug trials in Type 2 DM was compared with their percentage share in prevalence
      of Type 2 DM. DISCUSSION: A significant growth in the drug trials in Type 2 DM
      was observed during 2005 to 2008, after which there has been a plateau. It was
      also recognized that India and China which contribute to around 30% of diabetic
      population of the world contributed in only 9.73% and 5.15% of drug trials in
      Type 2 DM during 2010, respectively. USA comprising of 15.15% of diabetic
      population of world was seen to have contributed in 38.36% of clinical drug
      trials in Type 2 DM. This raises a question of skewing in the data generated from
      various drug trials conducted in Type 2 DM.

PMID- 21731858
TI  - Plagiarism: Why is it such a big issue for medical writers?
AB  - Plagiarism is the wrongful presentation of somebody else's work or idea as one's
      own without adequately attributing it to the source. Most authors know that
      plagiarism is an unethical publication practice. Yet, it is a serious problem in
      the medical writing arena. Plagiarism is perhaps the commonest ethical issue
      plaguing medical writing. In this article, we highlight the different types of
      plagiarism and address the issues of plagiarism of text, plagiarism of ideas,
      mosaic plagiarism, self-plagiarism, and duplicate publication. An act of
      plagiarism can have several repercussions for the author, the journal in question
      and the publication house as a whole. Sometimes, strict disciplinary action is
      also taken against the plagiarist. The article cites examples of retraction of
      articles, suspension of authors, apology letters from journal editors, and other
      such actions against plagiarism.

PMID- 21731859
TI  - The Nuremberg Code-A critique.
AB  - The Nuremberg Code drafted at the end of the Doctor's trial in Nuremberg 1947 has
      been hailed as a landmark document in medical and research ethics. Close
      examination of this code reveals that it was based on the Guidelines for Human
      Experimentation of 1931. The resemblance between these documents is uncanny. It
      is unfortunate that the authors of the Nuremberg Code passed it off as their
      original work. There is evidence that the defendants at the trial did request
      that their actions be judged on the basis of the 1931 Guidelines, in force in
      Germany. The prosecutors, however, ignored the request and tried the defendants
      for crimes against humanity, and the judges included the Nuremberg Code as a part
      of the judgment. Six of ten principles in Nuremberg Code are derived from the
      1931 Guidelines, and two of four newly inserted principles are open to
      misinterpretation. There is little doubt that the Code was prepared after
      studying the Guidelines, but no reference was made to the Guidelines, for reasons
      that are not known. Using the Guidelines as a base document without giving due
      credit is plagiarism; as per our understanding of ethics today, this would be
      considered unethical. The Nuremberg Code has fallen by the wayside; since unlike
      the Declaration of Helsinki, it is not regularly reviewed and updated. The
      regular updating of some ethics codes is evidence of the evolving nature of human
      ethics.

PMID- 21731860
TI  - Not only documentation.

PMID- 21731861
TI  - Geriatric endocrinology.

PMID- 21731862
TI  - Radiation exposure and cytotoxic endocrinopathy: It is time for action.

PMID- 21731863
TI  - Management of hyperglycemia in geriatric patients with diabetes mellitus: South
      Asian consensus guidelines.
AB  - Asia is home to four of the world's five largest diabetic populations, two of
      them being South Asian nations, namely, India and Pakistan. This problem is
      compounded by a substantial rise in the elderly population in Asian countries. On
      the other hand, the heterogeneous health condition and multiple co-morbidities
      make the care of chronic disease in the elderly a challenging task. The aim of
      the South Asian Consensus Guidelines is to provide evidence-based recommendations
      to assist healthcare providers in the rational management of type 2 diabetes
      mellitus in the elderly population. Current Guidelines used systematic reviews of
      available evidence to form its key recommendations. No evidence grading was done
      for the purpose of this manuscript. The clinical questions of the guidelines, the
      methodology of literature search, and medical writing strategy were finalized by
      consultations in person and through mail. The South Asian Consensus guideline
      emphasizes tailoring of glycemic goals for patients based on age, co-morbid
      conditions especially that of cardiovascular system, risk of hypoglycemia, and
      life expectancy. It also recommends cautious use of available pharmacotherapy in
      geriatric patients with diabetes. The primary principle of diabetes therapy
      should be to achieve euglycemia, without causing hypoglycemia. Appropriate use of
      modern insulins and oral drugs, including incretin mimetics will help physicians
      achieve this aim.

PMID- 21731864
TI  - Endocrine effects of Fukushima: Radiation-induced endocrinopathy.
AB  - The unfortunate accidents of Chernobyl and Fukushima have led to an enormous
      amount of radioactive material being released into the atmosphere. Radiation
      exposure to the human body may be as a result of accidents, such as those in
      Chernobyl and Fukushima, or due to occupational hazards, such as in the employees
      of nuclear plants, or due to therapeutic or diagnostic procedures. These
      different sources of radiations may affect the human body as a whole or may cause
      localized damage to a certain area of the body, depending upon the extent and
      dosage of the irradiation. More or less every organ is affected by radiation
      exposure. Some require a higher dose to be affected while others may be affected
      at a lower dose. All the endocrine glands are susceptible to damage by radiation
      exposure; however, pituitary, thyroid and gonads are most likely to be affected.
      In addition to the endocrine effects, the rates of birth defects and carcinomas
      may also be increased in the population exposed to excessive radiation.

PMID- 21731865
TI  - Nuclear detonation, thyroid cancer and potassium iodide prophylaxis.
AB  - The recent nuclear disaster at Japan has raised global concerns about effects of
      radioactive leakage in the environment, associated hazards, and how they can be
      prevented. In this article, we have tried to explain about the guidelines laid
      down by World Health Organization for a potassium iodide prophylaxis following a
      nuclear disaster, and its mechanism of action in preventing thyroid cancer. Data
      was collected mainly from the studies carried out during the Chernobyl disaster
      of Russia in 1986 and the hazardous effects especially on the thyroid gland were
      studied. It was seen that radioactive iodine leakage from the nuclear plants
      mainly affected the thyroid gland, and especially children were at a higher risk
      at developing the cancers. Potassium Iodide prophylaxis can be administered in
      order to prevent an increase in the incidence of thyroid cancers in the
      population of an area affected by a nuclear disaster. However, one has to be
      cautious while giving it, as using it without indication has its own risks.

PMID- 21731866
TI  - Evaluation of efficacy and safety of orlistat in obese patients.
AB  - CONTEXT: Rapidly rising prevalence of obesity is alarming. Obesity predisposes to
      co-morbidities like hypertension, type 2 diabetes mellitus, dyslipidemias, thus
      substantially rising healthcare expenditure. Lifestyle modifications alone have
      very limited success, necessitating the addition of pharmacotherapy to it.
      OBJECTIVE: Present study was carried out to evaluate the efficacy and safety of
      orlistat in obese patients. MATERIALS AND METHODS: Eighty obese (BMI>30) patients
      according to inclusion and exclusion criteria were randomized into either of the
      two groups. Group 1 received orlistat 120 mg three times a day and group 2
      received placebo three times a day. Weight, waist circumference, BMI, total
      cholesterol, triglycerides, HDL, LDL were measured at baseline and then at 8(th),
      16(th) and 24(th) week. ADR reported by patients were recorded. For safety
      evaluation various hematological and biochemical parameters were assessed. Z test
      was used for analysis of data. RESULTS: Compared to placebo, orlistat caused
      significant reduction (P<0.05) in weight (4.65 kg vs 2.5 kg; orlistat vs placebo,
      respectively), BMI (1.91 kg/m(2) vs 0.64 kg/m(2)) and waist circumference (4.84
      cm vs 2 cm), cholesterol (10.68 mg vs 6.18 mg) and LDL level (5.87 mg vs 2.33
      mg). In the orlistat group, the GI side effects like loose stools, oily
      stools/spotting, abdominal pain and fecal urgency were observed. CONCLUSION:
      Orlistat is an effective and well-tolerated antiobesity drug, which can be
      employed as an adjunct to therapeutic lifestyle changes to achieve and maintain
      optimal weight.

PMID- 21731867
TI  - Relationship of associated secondary hyperparathyroidism to serum fibroblast
      growth factor-23 in end stage renal disease: a case-control study.
AB  - INTRODUCTION: Secondary hyperparathyroidism (SHPT) is an insidious disease that
      develops early in the course of chronic kidney disease (CKD) and increases in
      severity as the glomerular filtration rate deteriorates. Recent studies have
      identified fibroblast growth factor-23 (FGF23) as a new protein with phosphaturic
      activity. It is mainly secreted by osteoblasts and is now considered the most
      important factor for regulation of phosphorus homeostasis. It is not yet proven
      if there is any direct relation between parathyroid hormone (PTH) and FGF23. The
      present study aims to evaluate the relation between serum FGF23, phosphorus, and
      PTH in end-stage renal disease in patients with SHPT on regular hemodialysis.
      MATERIALS AND METHODS: Forty-six consecutive CKD adult patients (case group) and
      20 healthy adults (control group) were included in the study. All patients had
      SHPT and were on regular hemodialysis. Both groups were subjected to full medical
      history, clinical examination and biochemical studies. Serum phosphorus, calcium,
      ferritin, hemoglobin level, blood urea, creatinine, PTH, and FGF23 were analyzed.
      RESULTS: Levels of FGF23 were significantly higher in the case group in
      comparison with those in the control group, viz., 4-fold, and positively
      correlated with PTH. Phosphorus levels in the case group were significantly high
      in spite of the increasing levels of FGF23. Both PTH and FGF23 were positively
      correlated with phosphorus and negatively with hemoglobin levels. CONCLUSION:
      SHPT and FGF23 may have a partial role in the development of anemia in patients
      with CKD. FGF23 could be a central factor in the pathogenesis of SHPT. Its role
      in controlling hyperphosphatemia in CKD is vague.

PMID- 21731868
TI  - Dyslipidemia as a contributory factor in etiopathogenesis of diabetic neuropathy.
AB  - OBJECTIVES: The pathogenesis of neuropathy in type 2 diabetes mellitus is
      multifactorial.Dyslipidemia may contribute to the development of diabetic
      neuropathy. This study aimed to assess the atherogenic lipid indices in type 2
      diabetic patients with neuropathy. MATERIAL AND METHODS: Fifty-one patients with
      type 2 diabetes mellitus and 31 healthy subjects were studied in the Unit of
      Neurophysiology at the University Hospital of Medical College, Al-Nahrin
      University in Baghdad, Iraq, from January 2002 to January 2003. Neuropathy total
      symptom score (NTSS), neuropathy impairment score in the lower leg (NIS-LL), and
      electrophysiological study of sensory (ulnar and sural) and motor (ulnar and
      common peroneal) nerves were used to assess nerve function. Fasting venous blood
      was obtained from each participant for determination of lipid profile and
      atherogenic lipid ratios. RESULTS: The frequency of high blood pressure was
      significantly higher in neuropathic patients. The electrophysiology study
      revealed significant decrease in conduction velocity of ulnar (sensory and motor
      components), sural, and common peroneal nerves. The minimum F-wave latency of
      motor nerve was significantly prolonged. Among the lipid fractions, only high
      density lipoprotein-cholesterol was significantly reduced by 14% of healthy
      participant's value. Atherogenic lipid ratios were significantly higher in
      diabetic patients than corresponding healthy ratios. CONCLUSION: Metabolic lipid
      disturbances in terms of atherogenicity co-existwith neuropathy in type 2
      diabetes mellitus, irrespective of duration of disease.

PMID- 21731869
TI  - Prevalence of neonatal hypothyroidism and phenylketonuria in Southern Thailand: A
      10-year report.
AB  - BACKGROUND: Congenital hypothyroidism and phenylketonuria, the two major problems
      of several metabolic errors are presently the focus of attention, in Thailand.
      These two conditions are assigned as diseases to be controlled under the National
      Public Health Policies of Thailand. MATERIALS AND METHODS: Here, the authors
      summarize and report the 10-year study on the prevalence of neonatal
      hypothyroidism and phenylketonuria in Southern Thailand. RESULTS: This report is
      good representative data from Thailand, a country in Southeast Asia. Another
      interesting point in this study is the concern of the recalling process.
      CONCLUSION: It can be seen that there are a considerable number of infants who
      did not receive the confirmation test due to loss of follow-up after calling for
      a recheck.

PMID- 21731870
TI  - State of endocrinology and diabetology in Brazil.
AB  - Brazil is a large, populous country in South America, which has one of the
      biggest concentrations of people with diabetes. This article reviews the current
      status of diabetes care, medical education and training, and diabetes/endocrine
      research in Brazil. It highlights achievements in public health and research,
      which can be emulated by other countries. In Endocrine/Diabetes fields, a more
      realistic and responsible policies in terms of medical traineeship, patient
      education, and mainly scientific production would be mandatory to raise Brazil to
      a global competitive level.

PMID- 21731871
TI  - Endocrinology in Thailand: Unique challenges, unique solutions.
AB  - Thailand is a developing country in Southeast Asia with a nationally acknowledged
      requirement for improvement of the medical system. At present, endocrinology is a
      specific branch of medicine that is taught in few medical schools. There are very
      few endocrinologists in Thailand, who are unable to cope with the large number of
      patients with endocrinology problems. Primary care for common endocrine
      disorders, such as diabetes mellitus and thyroid disease, is still the domain of
      general practitioners. In this article, the author will present unique challenges
      and unique solutions of endocrinology practice in Thailand.

PMID- 21731872
TI  - The anesthetic, critical care and surgical challenges in the management of
      craniopharyngioma.
AB  - Among the childhood brain neoplasms, craniopharyngioma constitutes about 2-6% of
      all primary intracranial tumors. Craniopharyngioma poses a multitude of
      challenges to the neurosurgeon, endocrinologist, oncologist, intensivist and the
      anesthesiologist. The morbidity and mortality due to radical surgical treatment
      is quite high, to the extent of 40-50%. The conservative approach with limited
      surgical intervention and radiotherapy assistance is taken by some neurosurgeons,
      but its usefulness is very doubtful. We are reporting a case of craniopharyngioma
      in an 18-year-old female who had progressive loss of vision and was successfully
      managed with combined radical surgery and medical therapy.

PMID- 21731873
TI  - 17-alpha-Hydroxylase deficiency: An unusual case with primary amenorrhea and
      hypertension.
AB  - A 14-year-old girl presented with acute onset quadriparesis and newly detected
      hypertension. Parental consanguinity, delayed puberty with normal stature form
      the additional information. Hypokalemia with metabolic alkalosis, low cortisol,
      high ACTH and FSH pointed to the possibility of CAH with 17alpha hydroxylase
      deficiency. 46XX karyotype and high progesterone supported this. Normalization of
      hypokalemia and hypertension with glucocorticoid treatment confirmed the
      diagnosis. In summary, the possibility of 17 OHD should be suspected in patients
      with hypokalemic myopathy, Hypertension and hypogonadism so that appropriate
      therapy can be implemented.

PMID- 21731874
TI  - A young lady with swelling and stiffness of calf muscles.
AB  - Hypothyroidism causes a variety of changes in the body. Though uncommon,
      hypothyroidism can present as myopathy. Hoffman's syndrome is a specific, rare
      form of hypothyroid myopathy, which causes proximal weakness and
      pseudohypertrophy of muscles.

PMID- 21731875
TI  - Metformin high dosage and bleeding episode: A clinical case study.
AB  - Although metformin is a widely used anti-diabetic drug, it has certain side
      effects. This case reports a bleeding episode which occurred after up- titration
      of metformin while trying to achieve adequate glycemic control.

PMID- 21731876
TI  - Cor pulmonale in a case of infantile Gaucher's disease.
AB  - Infantile Gaucher's disease presenting as cor pulmonale is rarely reported in
      pediatric literature. We report a 3.3 year old boy with infantile Gaucher's
      disease who presented to us as interstitial lung disease, pulmonary hypertension
      along with features of cor pulmonale. The high resolution CT findings were
      typical of interstitial and airspace disease. Cor pulmonale in this patient was a
      result of severe pulmonary hypertension.

PMID- 21731877
TI  - Cabergoline-induced tricuspid regurgitation: Case report and review of
      literature.
AB  - The increased risk of cardiac valve disease in patients treated for Parkinson's
      disease with cabergoline has raised concerns about the safety of treatment with
      ergot-derived dopamine agonists in patients with endocrine diseases, especially
      prolactinoma. Concern is raised because the use of cabergoline was associated in
      one study with an increased prevalence of moderate tricuspid regurgitation, and
      in two other studies with mild tricuspid regurgitation. Furthermore, the use of
      cabergoline was associated with increased frequencies of valvular thickening,
      calcifications, and increased mitral tenting area.

PMID- 21731878
TI  - Acromegaly associated with a symptomatic Rathke's cyst.
AB  - Our aim is to describe a case of acromegaly that was associated with symptomatic
      Rathke's cyst. We describe a young male student without any significant family
      history who presented with clinical and biochemical features consistent with
      growth hormone excess, which was confirmed with dynamic testing. He also
      described a persistent headache predating symptoms of growth hormone excess by 4
      years. Magnetic resonance imaging (MRI) of the pituitary showed a large sellar
      mass which was thought to be a somatotroph adenoma. Trans-sphenoidal surgery was
      performed; however, a colloid lesion was identified by the neurosurgeon that
      proved to be a Rathke's cyst. The association of acromegaly with Rathke's cyst is
      very rare, with less than 10 cases found to be reported on review of literature.
      This is the first report from India.

PMID- 21731879
TI  - Endocrine disruptors: Ubiquitous, yet less known.

PMID- 21731880
TI  - Loss of follow-up of diabetic patients: What are the reasons?

PMID- 21731881
TI  - Speech delays and behavioral problems are the predominant features in individuals
      with developmental delays and 16p11.2 microdeletions and microduplications.
AB  - Microdeletions and microduplications encompassing a ~593-kb region of 16p11.2
      have been implicated as one of the most common genetic causes of susceptibility
      to autism/autism spectrum disorder (ASD). We report 45 microdeletions and 32
      microduplications of 16p11.2, representing 0.78% of 9,773 individuals referred to
      our laboratory for microarray-based comparative genomic hybridization (aCGH)
      testing for neurodevelopmental and congenital anomalies. The microdeletion was de
      novo in 17 individuals and maternally inherited in five individuals for whom
      parental testing was available. Detailed histories of 18 individuals with 16p11.2
      microdeletions were reviewed; all had developmental delays with below-average
      intelligence, and a majority had speech or language problems or delays and
      various behavioral problems. Of the 16 individuals old enough to be evaluated for
      autism, the speech/behavior profiles of seven did not suggest the need for ASD
      evaluation. Of the remaining nine individuals who had speech/behavior profiles
      that aroused clinical suspicion of ASD, five had formal evaluations, and three
      had PDD-NOS. Of the 19 microduplications with parental testing, five were de
      novo, nine were maternally inherited, and five were paternally inherited. A
      majority with the microduplication had delayed development and/or specific
      deficits in speech or language, though these features were not as consistent as
      seen with the microdeletions. This study, which is the largest cohort of
      individuals with 16p11.2 alterations reported to date, suggests that 16p11.2
      microdeletions and microduplications are associated with a high frequency of
      cognitive, developmental, and speech delay and behavior abnormalities.
      Furthermore, although features associated with these alterations can be found in
      individuals with ASD, additional factors are likely required to lead to the
      development of ASD.

PMID- 21731882
TI  - Assessment of depression, anxiety and apathy in prodromal and early huntington
      disease.
AB  - The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a
      multinational, multidisciplinary initiative with the goal of developing a data
      driven, comprehensive, psychometrically sound, rating scale for assessing
      symptoms and functional ability in prodromal and early Huntington disease (HD)
      gene expansion carriers. The process involves input from numerous sources to
      identify relevant symptom domains, including HD individuals, caregivers, and
      experts from a variety of fields, as well as knowledge gained from the analysis
      of data from ongoing large-scale studies in HD using existing clinical scales.
      This is an iterative process in which an ongoing series of field tests in
      prodromal (prHD) and early HD individuals provides the team with data on which to
      make decisions regarding which questions should undergo further development or
      testing and which should be excluded. We report here the development and
      assessment of the first iteration of interview questions aimed to assess
      Depression, Anxiety and Apathy in prHD and early HD individuals.

PMID- 21731883
TI  - Locally Deformable Shape Model to Improve 3D Level Set based Esophagus
      Segmentation.
AB  - In this paper we propose a supervised 3D segmentation algorithm to locate the
      esophagus in thoracic CT scans using a variational framework. To address
      challenges due to low contrast, several priors are learned from a training set of
      segmented images. Our algorithm first estimates the centerline based on a spatial
      model learned at a few manually marked anatomical reference points. Then an
      implicit shape model is learned by subtracting the centerline and applying PCA to
      these shapes. To allow local variations in the shapes, we propose to use
      nonlinear smooth local deformations. Finally, the esophageal wall is located
      within a 3D level set framework by optimizing a cost function including terms for
      appearance, the shape model, smoothness constraints and an air/contrast model.

PMID- 21731884
TI  - Self-heating in piezoresistive cantilevers.
AB  - We report experiments and models of self-heating in piezoresistive
      microcantilevers that show how cantilever measurement resolution depends on the
      thermal properties of the surrounding fluid. The predicted cantilever temperature
      rise from a finite difference model is compared with detailed temperature
      measurements on fabricated devices. Increasing the fluid thermal conductivity
      allows for lower temperature operation for a given power dissipation, leading to
      lower force and displacement noise. The force noise in air is 76% greater than in
      water for the same increase in piezoresistor temperature.

PMID- 21731885
TI  - Effect of atorvastatin therapy on oxidant-antioxidant status and atherosclerotic
      plaque formation.
AB  - BACKGROUND: The aim of this study was to determine the oxidant-antioxidant status
      and lipid peroxidation products, as well as paraoxonase and atherosclerotic
      plaque formation, in a hypercholesterolemic atherosclerosis rabbit model to
      investigate the effects of atorvastatin in the atherosclerotic process. METHODS:
      Forty male New Zealand rabbits were divided into four groups, ie, a control group
      receiving standard pellets, a group receiving atorvastatin therapy, a
      hypercholesterolemic group receiving an atherogenic diet, and a group receiving
      both an atherogenic diet and atorvastatin. RESULTS: The atherogenic diet
      increased the levels of low-density lipoprotein (LDL) thiobarbituric acid
      reactive substances (1.84 vs 3.79 nmol/mg protein) and LDL-conjugated diene (147
      vs 318 MUmol/mg protein) after induction of oxidation by Cu(2+), despite an
      increase of superoxide dismutase activity. Treatment with atorvastatin limited
      LDL oxidation significantly (LDL thiobarbituric acid reactive substances 2.19
      nmol/mg protein, LDL-conjugated diene 222 MUmol/mg protein). Paraoxonase, which
      prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids, showed
      a pronounced decrease in the group receiving the atherogenic diet (110 U/L to 28
      U/L), and atorvastatin treatment increased paraoxonase activity. Histological
      examination of arcus aorta tissues from the hypercholesterolemic group showed
      abundant plaque formation surrounding and obstructing the lumen, whereas
      treatment with atorvastatin prevented or limited plaque formation, keeping the
      plaque thin and localized. CONCLUSION: Atorvastatin has dramatic
      antiatherosclerotic effects, part of which seems to be due to the antioxidant
      features of the parent drug and/or its metabolites, favoring inhibition of LDL
      oxidation.

PMID- 21731886
TI  - Stentless aortic valve replacement: an update.
AB  - Although porcine aortic valves or pericardial tissue mounted on a stent have made
      implantation techniques easier, these valves sacrifice orifice area and increase
      stress at the attachment of the stent, which causes primary tissue failure.
      Optimizing hemodynamics to prevent patient-prosthetic mismatch and improve
      durability, stentless bioprostheses use was revived in the early 1990s. The
      purpose of this review is to provide a current overview of stentless valves in
      the aortic position. Retrospective and prospective randomized controlled studies
      showed similar operative mortality and morbidity in stented and stentless aortic
      valve replacement (AVR), though stentless AVR required longer cross-clamp and
      cardiopulmonary bypass time. Several cohort studies showed improved survival
      after stentless AVR, probably due to better hemodynamic performance and earlier
      left ventricular (LV) mass regression compared with stented AVR. However, there
      was a bias of operation age and nonrandomization. A randomized trial supported an
      improved 8-year survival of patients with the Freestyle or Toronto valves
      compared with Carpentier-Edwards porcine valves. On the contrary, another
      randomized study did not show improved clinical outcomes up to 12 years. Freedom
      from reoperation at 12 years in Toronto stentless porcine valves ranged from 69%
      to 75%, which is much lower than for Carpentier-Edwards Perimount valves. Cusp
      tear with consequent aortic regurgitation was the most common cause of structural
      valve deterioration. Cryolife O'Brien valves also have shorter durability
      compared with stent valves. Actuarial freedom from reoperation was 44% at 10
      years. Early prosthetic valve failure was also reported in patients who underwent
      root replacement with Shelhigh stentless composite grafts. There was no level I
      or IIa evidence of more effective orifice area, mean pressure gradient, LV mass
      regression, surgical risk, durability, and late outcomes in stentless
      bioprostheses. There is no general recommendation to prefer stentless
      bioprostheses in all patients. For new-generation pericardial stentless valves,
      follow-up over 15 years is necessary to compare the excellent results of stented
      valves such as the Carpentier-Edwards Perimount and Hancock II valves.

PMID- 21731887
TI  - Aldosterone and aldosterone receptor antagonists in patients with chronic heart
      failure.
AB  - Aldosterone is a mineralocorticoid hormone synthesized by the adrenal glands that
      has several regulatory functions to help the body maintain normal volume status
      and electrolyte balance. Studies have shown significantly higher levels of
      aldosterone secretion in patients with congestive heart failure compared with
      normal patients. Elevated levels of aldosterone have been shown to elevate blood
      pressure, cause left ventricular hypertrophy, and promote cardiac fibrosis. An
      appreciation of the true role of aldosterone in patients with chronic heart
      failure did not become apparent until the publication of the Randomized Aldactone
      Evaluation Study. Until recently, the use of aldosterone receptor antagonists has
      been limited to patients with severe heart failure and patients with heart
      failure following myocardial infarction. The Eplerenone in Mild Patients
      Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) study added
      additional evidence to support the expanded use of aldosterone receptor
      antagonists in heart failure patients. The results of the EMPHASIS-HF trial
      showed that patients with mild-to-moderate (New York Heart Association Class II)
      heart failure had reductions in mortality and hospitalizations from the addition
      of eplerenone to optimal medical therapy. Evidence remains elusive about the
      exact mechanism by which aldosterone receptor antagonists improve heart failure
      morbidity and mortality. The benefits of aldosterone receptor antagonist use in
      heart failure must be weighed against the potential risk of complications, ie,
      hyperkalemia and, in the case of spironolactone, possible endocrine
      abnormalities, in particular gynecomastia. With appropriate monitoring, these
      risks can be minimized. We now have evidence that patients with mild-to-severe
      symptoms associated with systolic heart failure will benefit from the addition of
      an aldosterone receptor antagonist to the standard therapies of angiotensin
      converting enzyme inhibitors and beta-blockers. This review will address the
      pharmacologic basis of aldosterone receptor antagonists in patients with heart
      failure and the clinical impact of this therapy.

PMID- 21731888
TI  - Chasing the reflected wave back into the heart: a new hypothesis while the jury
      is still out.
AB  - BACKGROUND: Arterial stiffness directly influences cardiac function and is
      independently associated with cardiovascular risk. However, the influence of the
      aortic reflected pulse pressure wave on left ventricular function has not been
      well characterized. The aim of this study was to obtain detailed information on
      regional ventricular wall motion patterns corresponding to the propagation of the
      reflected aortic wave on ventricular segments. METHODS: Left ventricular wall
      motion was investigated in a group of healthy volunteers (n = 14, age 23 +/- 3
      years), using cardiac magnetic resonance navigator-gated tissue phase mapping.
      The left ventricle was divided into 16 segments and regional wall motion was
      studied in high temporal detail. RESULTS: Corresponding to the expected timing of
      the reflected aortic wave reaching the left ventricle, a characteristic "notch"
      of regional myocardial motion was seen in all radial, circumferential, and
      longitudinal velocity graphs. This notch was particularly prominent in septal
      segments adjacent to the left ventricular outflow tract on radial velocity graphs
      and in anterior and posterior left ventricular segments on circumferential
      velocity graphs. Similarly, longitudinal velocity graphs demonstrated a brief
      deceleration in the upward recoil motion of the entire ventricle at the beginning
      of diastole. CONCLUSION: These results provide new insights into the possible
      influence of the reflected aortic waves on ventricular segments. Although the
      association with the reflected wave appears to us to be unambiguous, it
      represents a novel research concept, and further studies enabling the actual
      recording of the pulse wave are required.

PMID- 21731889
TI  - Stiffness of the large arteries in individuals with and without Down syndrome.
AB  - BACKGROUND: Down syndrome is known to cause premature aging in several organ
      systems. However, it remains unclear whether this aging effect also affects the
      structure and function of the large arterial trunks. In this controlled study,
      the possibility of changes in the large arteries due to aging was evaluated in
      patients with Down syndrome. METHODS: Eighty-two subjects of both genders were
      selected. The Down syndrome group had 41 active subjects consisting of 19 males
      and 22 females (mean age 21 +/- 1, range 13-42 years) without cardiovascular
      complications and who did not use vasoactive drugs. The control group consisted
      of 41 healthy individuals without trisomy 21 of the same gender and age as the
      Down syndrome group and who did not use vasoactive medication. Carotid-femoral
      pulse wave velocity was obtained as an index of aortic stiffness using an
      automatic noninvasive method. RESULTS: Individuals with Down syndrome had
      significantly lower blood pressure than those in the control group. Systolic
      blood pressure for the Down syndrome group and control group was 106 +/- 2 mmHg
      vs 117 +/- 2 mmHg (P < 0.001), respectively; diastolic blood pressure was 66 +/-
      2 mmHg vs 77 +/- 2 mmHg (P < 0.001); and mean arterial pressure was 80 +/- 1 mmHg
      vs 90 +/- 1 mmHg (P < 0.001). Only age and systolic blood pressure were shown to
      correlate significantly with pulse wave velocity, but the slopes of the linear
      regression curves of these two variables showed no significant difference between
      the two study groups. Pulse wave velocity, which was initially significantly
      lower in the Down syndrome group (7.51 +/- 0.14 m/s vs 7.84 +/- 0.12 m/s; P
      <0.05), was similar between the groups after systolic blood pressure adjustment
      (7.62 +/- 0.13 m/s vs 7.73 +/- 0.13 m/s). CONCLUSION: Despite evidence in the
      literature that patients with Down syndrome undergo early aging, this process
      does not seem to affect the large arterial trunks, given that values of carotid
      femoral pulse wave velocity were similar in individuals with or without trisomy
      21. Considering that Down syndrome presents with chronic hypotension, it is
      reasonable to propose that the prolonged reduction of arterial distending
      pressure may contribute to functional preservation of the arteries in patients
      with Down syndrome.

PMID- 21731890
TI  - Association of an overlap syndrome of autoimmune hepatitis and primary biliary
      cirrhosis with cytomegalovirus infection.
AB  - A 63-year-old woman, who presented with severe jaundice and elevated serum
      conjugated bilirubin level, denied alcohol and drug use and showed no evidence of
      viral hepatitis. Based on clinical and laboratory features, she was diagnosed
      with autoimmune hepatitis with primary biliary cirrhosis. Hematological and
      immunochemical assays, radiographic imaging, clinical examination, and liver
      biopsy were conducted. Laboratory results were the following: negative for
      fluorescence antinuclear antibody, negative for antismooth muscle antibodies but
      positive for antinuclear antibody (enzyme-linked immunosorbent assay) and
      antimitochondrial M2 antibody, high titers of serum globulin, and positive for
      cytomegalovirus IgM. Liver biopsy showed submassive lobular necrosis,
      inflammation with broad areas of parenchymal collapse, and chronic nonsuppurative
      destructive cholangitis. The patient responded well to corticosteroid therapy.
      This case might illustrate an association between cytomegalovirus infection and
      the occurrence of autoimmune hepatitis.

PMID- 21731891
TI  - Differences in maintenance of mean blood glucose (BG) and their association with
      response to "recognizing hunger".
AB  - BACKGROUND: Meals begin and end subjectively. We trained healthy subjects to
      recognize initial hunger as a preprandial target for meal consumption, and to
      create a "recognizing hunger" or initial hunger meal pattern. OBJECTIVE: Training
      subjects to "recognize hunger" lowers blood glucose (BG) and improves energy
      balance, and lowers metabolic risks and bodyweight. A minority may have low BG
      and low metabolic risks at recruitment, but the others may recover this favorable
      condition by training. METHODS: In a 7-day food diary, subjects reported their
      preprandial BG measurements; BG and energy availability by blood were assessed at
      the lowest BG during the day, and diary-mean BG thus characterized the individual
      meal pattern (daily energy intake). We analyzed the same diaries of a recent
      paper on a global, randomized comparison of subjects trained in "recognizing
      hunger" with control subjects. This time, we checked whether subjects who had
      maintained low BG (LBG subgroup) at recruitment were able to decrease mean BG and
      metabolic risk factors during "hunger recognition" like those who presented high
      BG (HBG subgroup). RESULTS: At recruitment, the BG means of 120 investigated
      subjects were within mean confidence limits of +/- 3.84 mg/dL, and we could
      stratify subjects in ten small strata of which each significantly differed by
      mean BG. Mean BG was stable in each control subject over five months; the mean
      absolute change being 6.0 +/- 4.6 mg/dL. Only three out of 34 trained subjects
      who had lower mean BG than 81.8 mg/dL significantly decreased mean BG, whereas 41
      out of 55 subjects whose mean BG was greater than 81.8 mg/dL significantly
      decreased mean BG after training (P < 0.0001). At recruitment, the LBG subgroup
      showed significantly lower insulin, lower BG area under curve (AUC) in the oral
      glucose tolerance test (GTT), and lower HbA1c than the HBG group. After training,
      only HBG subjects, compared with HBG controls, significantly decreased
      preprandial BG from 91.6 +/- 7.7 mg/dL to 81.0 +/- 7.7 mg/dL, in association with
      a decrease of HbA1c from 4.81% +/- 0.44% to 4.56% +/- 0.47%, of GTT insulin AUC
      from 244 +/- 138 mU/L to 164 +/- 92 mU/L, and of energy intake from 1872 +/- 655
      kcal to 1251 +/- 470 kcal (P < 0.001), with an increase of indices of insulin
      sensitivity from 5.9 +/- 3.3 to 9.8 +/- 5.6 and of beta cell function from 1.0 +/
      0.7 to 1.4 +/- 1.1 (P < 0.05). LBG subjects only decreased weekly-diary BG
      standard deviation in comparison with controls. CONCLUSION: At recruitment, the
      120 subjects maintained mean BG at one personal level of ten possibilities, and
      34 subjects were below 81.8 mg/dL (LBG) and 55 were over (HBG). The 55 HBG
      subjects showed higher mean insulin resistance, HbA1c, other cardiovascular risk
      factors, and increased bodyweight compared with the 34 LBG subjects. A total of
      41 out of the 55 HBG subjects regressed to LBG with training.

PMID- 21731892
TI  - Sulfur mustard induces expression of metallothionein-1A in human airway
      epithelial cells.
AB  - BACKGROUND: Sulfur mustard can cause several long-term complications in the
      organs of individuals exposed to this toxic gas, and among these, pulmonary
      sequelae are the most important. More than 25 years after the Iran-Iraq war,
      thousands of Iranians are suffering from the chronic respiratory complications of
      sulfur mustard. Currently, based on several clinical findings, bronchiolitis
      obliterans is confirmed as the major diagnosis in these patients. Numerous
      studies have revealed that this disorder is strongly associated with oxidative
      stress due to excessive production of harmful reactive substances and decreased
      levels of endogenous antioxidants. Metallothioneins (MTs) are a group of low
      molecular weight sulfhydryl-rich intra-cellular proteins, and several isoforms
      have been identified in humans. MT-1A is an inducible and important MT isoform,
      which is transcriptionally activated by a variety of stress stimuli, such as free
      radicals. METHODS: MT-1 mRNA expression and protein levels in endobronchial
      biopsy samples from 24 sulfur mustard-exposed patients and 15 unexposed control
      cases were evaluated by semi-quantitative reverse transcriptase polymerase chain
      reaction, real-time reverse transcriptase polymerase chain reaction, and
      immunohistochemistry. RESULTS: mRNA- MT-1A expression levels in sulfur mustard
      exposed patients were upregulated compared with normal samples. Protein
      expression was also markedly higher in controls than in sulfur mustard-exposed
      patients. CONCLUSION: Upregulation of MT-1A mRNA in patients who have been
      exposed to sulfur mustard seems to be due to oxidative stress, which is induced
      in an attempt to ameliorate this harmful situation by reestablishment of
      homeostasis, but depletion of its protein might be due to secondary consequences
      of sulfur mustard toxicity, which are as yet not understood.

PMID- 21731893
TI  - Acute otitis media in children.
AB  - CLINICAL QUESTION: What is the best treatment for acute otitis media in children?
      RESULTS: Watchful waiting, followed by amoxicillin treatment, if necessary, is
      the best first-line treatment for acute otitis media in children aged six months
      or older.

PMID- 21731895
TI  - Abdominal wall desmoid tumor mimicking a subserosal uterine leiomyoma.
AB  - Desmoid tumors are cytologically bland fibrous neoplasms originating from
      musculoaponeurotic structures throughout the body. The cause of desmoid tumors is
      uncertain, but may be related to trauma or hormonal factors, or may have a
      genetic association. These tumors can be found in some young women during
      pregnancy or just after giving birth. We report herein a case of desmoid tumor on
      the inner aspect of the abdominal wall that mimicked a large subserosal uterine
      leiomyoma. Initial clinical examination of the patient suggested a large
      abdominal wall tumor, while the imaging techniques including transabdominal
      ultrasound and magnetic resonance imaging suggested a large subserosal uterine
      leiomyoma as the initial diagnosis. This case emphasizes the importance of
      clinical examination during the diagnostic process.

PMID- 21731896
TI  - Walking just after a meal seems to be more effective for weight loss than waiting
      for one hour to walk after a meal.
AB  - There is a belief that walking just after a meal causes fatigue, stomach ache,
      and other types of discomfort. However, the author and one volunteer participant
      had no such negative reactions, and found that walking just after a meal was more
      effective for weight loss than waiting one hour after eating before walking. For
      people who do not experience abdominal pain, fatigue, or other discomfort when
      walking just after a meal, walking at a brisk speed for 30 minutes as soon as
      possible just after lunch and dinner leads to more weight loss than does walking
      for 30 minutes beginning one hour after a meal has been consumed. The author lost
      nearly 3 kg and a volunteer participant lost nearly 1.5 kg during one month of
      walking just after lunch and dinner. The author walked at a brisk pace, while the
      volunteer walked at a stroll. We repeated the preliminary experiment twice,
      between April and early May 2002, and once between August and September 2006, and
      obtained the same results.

PMID- 21731894
TI  - Sleep and its importance in adolescence and in common adolescent somatic and
      psychiatric conditions.
AB  - Restoring sleep is strongly associated with a better physical, cognitive, and
      psychological well-being. By contrast, poor or disordered sleep is related to
      impairment of cognitive and psychological functioning and worsened physical
      health. These associations are well documented not only in adults but also in
      children and adolescents. Importantly, adolescence is hallmarked by dramatic
      maturational changes in sleep and its neurobiological regulation, hormonal
      status, and many psychosocial and physical processes. Thus, the role of sleep in
      mental and physical health during adolescence and in adolescent patients is
      complex. However, it has so far received little attention. This review first
      presents contemporary views about the complex neurobiology of sleep and its
      functions with important implications for adolescence. Second, existing complex
      relationships between common adolescent somatic/organic, sleep-related, and
      psychiatric disorders and certain sleep alterations are discussed. It is
      concluded that poor or altered sleep in adolescent patients may trigger and
      maintain many psychiatric and physical disorders or combinations of these
      conditions, which presumably hinder recovery and may cross into later stages of
      life. Therefore, timely diagnosis and management of sleep problems appear
      critical for growth and development in adolescent patients.

PMID- 21731897
TI  - Pilot study of the efficacy and safety of lettuce seed oil in patients with sleep
      disorders.
AB  - BACKGROUND: Lactuca sativa (garden lettuce) is a popular salad herb. It has been
      in use in folk medicine since ancient times as both an appetite stimulant and as
      an aid to sleep. L. sativa seed oil (Sedan((r))) has demonstrated a pronounced
      sedative effect and potentiated the hypnotic effect of barbiturates in animal
      models. It also exhibited significant analgesic and anti-inflammatory activities.
      In this study, we evaluated the sedative and hypnotic effects of L. sativa in
      patients suffering from insomnia. METHODS: Sixty patients suffering from insomnia
      with or without anxiety were randomized to receive capsules containing L. sativa
      seed oil 1000 mg (n = 30) or placebo (n = 30). All patients were asked to
      complete a verbal questionnaire before the start of the trial and 1 week after
      starting treatment. RESULTS: Improvements in the modified State-Trait Anxiety
      Inventory and the Sleep rating scale scores were significantly greater in
      patients receiving L. sativa seed oil compared with those on placebo (P < 0.05).
      No side effects were found to be attributable to L. sativa seed oil at the given
      dosage. CONCLUSION: L. sativa seed oil was found to be a useful sleeping aid and
      may be a hazard-free line of treatment, especially in geriatric patients
      suffering from mild-to-moderate forms of anxiety and sleeping difficulties.

PMID- 21731898
TI  - Pharmacological enhancement of naltrexone treatment for opioid dependence: a
      review.
AB  - PURPOSE: Opioid dependence (OD) is a serious and growing clinical condition with
      increasing social costs that requires expanding treatment beyond opioid agonist
      substitution. The opioid antagonist naltrexone has displayed a remarkable
      association of theoretical effectiveness and poor clinical utility in treating OD
      due to noncompliant behavior and low acceptability among patients, only partly
      modified by psychosocial interventions. We reviewed pharmacological studies,
      including naltrexone depot formulations and combination treatments. METHOD: We
      searched PubMed for clinical studies on the use of naltrexone implants and slow
      release injections in OD, and investigations using adjunct medications to improve
      naltrexone maintenance therapy of OD. We discussed the results in view of their
      application to the clinical practice. RESULTS: Significant reduction in opioid
      use and improved retention in treatment have been found in several studies using
      depot naltrexone formulations, some of which are controlled clinical trials.
      Pilot investigations have gathered initial positive results on the use of
      naltrexone in combination with serotonin reuptake inhibitors, alpha-2 adrenergic,
      opioid, and gamma-aminobutyric acid agonist medications. CONCLUSION: Current
      evidence suggests that more research on effectiveness and safety is needed in
      support of depot naltrexone treatment for OD. Further research comparing slow
      release with oral naltrexone and opioid agonist medications will help
      characterize the role of opioid antagonist-mediated treatment of OD. Preliminary
      investigations on naltrexone combination treatments suggest the opportunity to
      continue study of new mixed receptor activities for the treatment of OD and other
      drug addictions.

PMID- 21731899
TI  - What You Hear and What You Say: Language Performance in Spanish English
      Bilinguals.
AB  - PURPOSE: This study assesses the factors that contribute to Spanish and English
      language development in bilingual children. METHOD: 757 Hispanic Pre-kindergarten
      and kindergarten age children completed screening tests of semantic and
      morphosyntactic development in Spanish and English. Parents provided information
      about their occupation and education as well as their children's English and
      Spanish exposure. Data were analyzed using zero-inflated regression models
      (comprising a logistic regression component and a negative binomial or Poisson
      component) to explore factors that contributed to children initiating L1 and L2
      performance and factors that contributed to building children's knowledge.
      RESULTS: Factors that were positively associated with initiating L1 and L2
      performance were language input/output, free and reduced lunch, and age. Factors
      associated with building knowledge included age, parent education, input/output,
      free and reduced lunch and school district. CONCLUSION: Amount of language input
      is important as children begin to use a language, and amount of language output
      is important for adding knowledge to their language. Semantic development seemed
      to be driven more by input while morphosyntax development relied on both input
      and output. Clinicians who assess bilingual children should examine children's
      language output in their second language to better understand their levels of
      performance.

PMID- 21731900
TI  - Thiolene-based microfluidic flow cells for surface plasmon resonance imaging.
AB  - Thiolene-based microfluidic devices have been coupled with surface plasmon
      resonance imaging (SPRI) to provide an integrated platform to study interfacial
      interactions in both aqueous and organic solutions. In this work, we develop a
      photolithographic method that interfaces commercially available thiolene resin to
      gold and glass substrates to generate microfluidic channels with excellent
      adhesion that leave the underlying sensor surface free from contamination and
      readily available for surface modification through self-assembly. These devices
      can sustain high flow rates and have excellent solvent compatibility even with
      several organic solvents. To demonstrate the versatility of these devices, we
      have conducted nanomolar detection of streptavidin-biotin interactions using in
      situ SPRI.

PMID- 21731902
TI  - Definition, epidemiology and magnitude of alcoholic hepatitis.
AB  - Alcoholic liver disease (ALD) is a major cause of alcohol-related morbidity and
      mortality. Its presentation ranges from fatty liver to alcoholic hepatitis (AH),
      cirrhosis, and hepatocellular carcinoma. Although the amount and pattern of
      alcohol consumption is a well recognized predisposing factor for the development
      of serious liver pathology, environmental factors and the host's genetic make-up
      may also play significant roles that have not yet been entirely explored.
      Continuing alcohol consumption is a major factor that influences the survival of
      patients with AH. The presence of cirrhosis at presentation or its development on
      follow up is a major factor determining the outcome in the long run. This chapter
      deals with the epidemiology and magnitude of ALD in general and AH in particular.

PMID- 21731901
TI  - Insulin resistance and chronic liver disease.
AB  - Increased insulin resistance is frequently associated with chronic liver disease
      and is a pathophysiological feature of hepatogenous diabetes. Distinctive factors
      including hepatic parenchymal cell damage, portal-systemic shunting and hepatitis
      C virus are responsible for the development of hepatogenous insulin
      resistance/diabetes. Although it remains unclear whether insulin secretion from
      pancreatic beta cells is impaired as it is in type 2 diabetes, retinopathic and
      cardiovascular risk is low and major causes of death in cirrhotic patients with
      diabetes are liver failure, hepatocellular carcinoma and gastrointestinal
      hemorrhage. Hemoglobin A1c is an inaccurate marker for the assessment and
      management of hepatogenous diabetes. Moreover, exogenous insulin or sulfonylureas
      may be harmful because these agents may promote hepatocarcinogenesis. Thus,
      pathogenesis, cause of death, assessment and therapeutic strategy for
      hepatogenous insulin resistance/diabetes differ from those for lifestyle-related
      type 2 diabetes. In this article, we review features of insulin resistance in
      relationship to chronic liver disease. We also discuss the impact of anti
      diabetic agents on interferon treatment and hepatocarcinogenesis.

PMID- 21731903
TI  - Pathogenesis of alcoholic hepatitis: Role of inflammatory signaling and oxidative
      stress.
AB  - Inflammatory signaling and oxidative stress are two major components in the
      pathogenesis of alcoholic hepatitis. Alcohol consumption results in translocation
      of gut bacteria into the portal system along with lipopolysaccharides that
      interact with toll-like receptors and results in the production of inflammatory
      and immunogenic mediators such as tumor necrosis factor-alpha (TNF-alpha) and
      interferons. Chronic consumption of alcohol causes priming of this process in
      which there is enhanced production of cytokines, interferon, interleukins, and
      TNF-alpha. Oxidative stress, genetic predisposition, and the unfolded protein
      response are other contributory mechanisms. Novel therapies aimed at these
      pathways may prevent, decrease, or delay the complications of alcoholic
      hepatitis.

PMID- 21731904
TI  - Symptoms and signs of acute alcoholic hepatitis.
AB  - Although there is not one specific sign or symptom related to alcoholic hepatitis
      (AH), a constellation of symptoms and signs can help make the diagnosis of AH
      with reasonable accuracy. Documentation of chronic and active alcohol abuse is
      paramount in making a diagnosis of AH. Clinical presentation after abstinence for
      more than 3 m should raise doubts about the diagnosis of AH and dictate the need
      for considering other causes of liver disease, decompensation of alcoholic
      cirrhosis, sepsis and malignancy as the cause of patient's clinical profile.

PMID- 21731905
TI  - Acute renal dysfunction in patients with alcoholic hepatitis.
AB  - Acute renal dysfunction is common in patients with alcoholic hepatitis (AH). Its
      presence leads to higher mortality in these patients. Despite advances in medical
      care, the outcome has changed little over the past decades. Studies using
      Pentoxifylline and molecular adsorbent recirculation system have shown
      encouraging data in small studies. Further larger well designed studies are
      needed to assess these modalities of treatment for the treatment of AH.

PMID- 21731906
TI  - General aspects of the treatment of alcoholic hepatitis.
AB  - General measures for treating patients with alcoholic hepatitis (AH) are similar
      irrespective of the disease severity. Alcohol abstinence is the cornerstone of
      treatment and can be achieved with appropriate social support, Alcoholics
      Anonymous and sometimes pharmacological therapy. Alcohol withdrawal should be
      anticipated and treatment initiated to prevent this complication. Treatment for
      complications of cirrhosis should be as for any other patient with cirrhosis. AH
      patients are particularly prone to infections and malnutrition. These should be
      identified and treated appropriately using broad spectrum antibiotics and
      nutritional support respectively.

PMID- 21731907
TI  - Bacteremia and "Endotipsitis" following transjugular intrahepatic portosystemic
      shunting.
AB  - AIM: To identify all cases of bacteremia and suspected endotipsitis after
      Transjugular intrahepatic portosystemic shunting (TIPS) at our institution and to
      determine risk factors for their occurrence. METHODS: We retrospectively reviewed
      records of all patients who underwent TIPS in our institution between 1996 and
      2009. Data included: indications for TIPS, underlying liver disease,
      demographics, positive blood cultures after TIPS, microbiological
      characteristics, treatment and outcome. RESULTS: 49 men and 47 women were
      included with a mean age of 55.8 years (range 15-84). Indications for TIPS
      included variceal bleeding, refractory ascites, hydrothorax and hepatorenal
      syndrome. Positive blood cultures after TIPS were found in 39/96 (40%) patients
      at various time intervals following the procedure. Seven patients had persistent
      bacteremia fitting the definition of endotipsitis. Staphylococcus species grew in
      66% of the positive cultures, Candida and enterococci species in 15% each of the
      isolates, and 3% cultures grew other species. Multi-variate regression analysis
      identified 4 variables: hypothyroidism, HCV, prophylactic use of antibiotics and
      the procedure duration as independent risk factors for positive blood cultures
      following TIPS (P < 0.0006, 0.005, 0.001, 0.0003, respectively). Prophylactic use
      of antibiotics before the procedure was associated with a decreased risk for
      bacteremia, preventing mainly early infections, occurring within 120 d of the
      procedure. CONCLUSION: Bacteremia is common following TIPS. Risk factors
      associated with bacteremia include failure to use prophylactic antibiotics,
      hypothyroidism, HCV and a long procedure. Our results strongly support the use of
      prophylaxis as a means to decrease early post TIPS infections.

PMID- 21731908
TI  - Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors
      in gastrointestinal cancer.
AB  - Matrix metalloproteinases (MMPs) are implicated in cancer development and
      progression and are associated with prognosis. Single-nucleotide polymorphisms
      (SNPs) of MMPs, most frequently located in the promoter region of the genes, have
      been shown to influence cancer susceptibility and/or progression. SNPs of MMP-1, 
      2, -3, -7, -8, -9, -12, -13 and -21 and of the tissue inhibitor of
      metalloproteinases (TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract
      tumors. The contribution of these polymorphisms to the cancer risk and prognosis
      of gastrointestinal tumors are reviewed in this paper.

PMID- 21731909
TI  - Recurrent renal cell cancer presenting as gastrointestinal bleed.
AB  - We present an unusual case of renal cell cancer (RCC) which relapsed with
      duodenal metastasis and unveiled itself by gastrointestinal (GI) bleeding. An 80
      year old Caucasian gentleman with history of renal cell cancer status post
      nephrectomy 11 mo previously, presented with syncope and melena. Computed
      tomography scan of the abdomen revealed heterogeneous soft tissue mass in the
      right nephrectomy bed invading the duodenum. Upper GI endoscopic biopsy confirmed
      the presence of recurrent renal cell cancer. However, due to extensive metastatic
      disease, the patient was placed on palliative chemotherapy as surgical options
      were ruled out. Our case report reiterates the fact that renal cell carcinoma can
      recur with gastrointestinal manifestations and, although a rarity, it should be
      considered in a patient with a history of malignancy who presents with these
      symptoms.

PMID- 21731910
TI  - Adult intussusception secondary to an ileum hamartoma.
AB  - Intussusception is a rare condition in the adult population. However, in contrast
      to its presentation in children, an identifiable etiology is found in the
      majority of cases. Clinical manifestations of adult intussusception are non
      specific and patients may present with acute, intermittent or chronic symptoms,
      predominantly those of intestinal obstruction. A 27-year-old male patient with
      recurrent abdominal pain secondary to intussusception is herein reported. The
      clinical presentation and ultrasonographic findings led to the diagnosis. At
      laparotomy, an ileal hamartoma was found as the lead point of the
      intussusception. Surgical management and histopathologic studies are described. A
      recurrent intestinal obstruction and classic ultrasound findings may lead to the
      diagnosis of intussusception but surgical exploration remains essential. The
      principle of resection without reduction is well established.

PMID- 21731911
TI  - Genetic relationships between Candida albicans strains isolated from dental
      plaque, trachea, and bronchoalveolar lavage fluid from mechanically ventilated
      intensive care unit patients.
AB  - Candida albicans often resides in the oral cavity of healthy humans as a harmless
      commensal organism. This opportunistic fungus can cause significant disease in
      critically ill patients, such as those undergoing mechanical ventilation in the
      intensive care unit (ICU) having compromised local airway defense mechanisms. The
      goal of this study was to determine the intra- and inter-patient genetic
      relationship between strains of C. albicans recovered from dental plaque,
      tracheal secretions, and the lower airway by bronchoalveolar lavage of patients
      undergoing mechanical ventilation. Three pulsed-field gel electrophoresis (PFGE)
      typing methods were used to determine the genetic relatedness of the C. albicans
      strains, including electrophoretic karyotyping (EK) and restriction endonuclease
      analysis of the genome using SfiI (REAG-S) and BssHII (REAG-B). The C. albicans
      isolates from dental plaque and tracheo-bronchial sites from the same patient
      were genetically indistinguishable and retained over time, whereas strains from
      different patients usually separated into different genotypes. Among the three
      methods, REAG-B proved to be the most discriminatory method to differentiate
      isolates. The finding of genetically similar strains from the oral and tracheo
      bronchial sites from the same patient supports the notion that the oral cavity
      may serve as an important source for C. albicans spread to the trachea and lung
      of mechanically ventilated patients.

PMID- 21731912
TI  - Detection of Streptococcus mutans Genomic DNA in Human DNA Samples Extracted from
      Saliva and Blood.
AB  - Caries is a multifactorial disease, and studies aiming to unravel the factors
      modulating its etiology must consider all known predisposing factors. One major
      factor is bacterial colonization, and Streptococcus mutans is the main
      microorganism associated with the initiation of the disease. In our studies, we
      have access to DNA samples extracted from human saliva and blood. In this report,
      we tested a real-time PCR assay developed to detect copies of genomic DNA from
      Streptococcus mutans in 1,424 DNA samples from humans. Our results suggest that
      we can determine the presence of genomic DNA copies of Streptococcus mutans in
      both DNA samples from caries-free and caries-affected individuals. However, we
      were not able to detect the presence of genomic DNA copies of Streptococcus
      mutans in any DNA samples extracted from peripheral blood, which suggests the
      assay may not be sensitive enough for this goal. Values of the threshold cycle of
      the real-time PCR reaction correlate with higher levels of caries experience in
      children, but this correlation could not be detected for adults.

PMID- 21731913
TI  - Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?
AB  - Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly
      effective and relatively safe agents for the treatment of a variety of
      gastrointestinal disorders. Unfortunately, this desirable pharmacological profile
      has also contributed to superfluous and widespread use in both the inpatient and
      outpatient settings. While generally well-tolerated, research published over the
      last decade has associated these agents with increased risks of Clostridium
      difficile disease, fractures likely due to calcium malabsorption and both
      community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism
      behind PPI-associated pneumonia may be multifactorial, but is thought to stem
      from compromising the stomach's "acid mantle" against gastric colonization of
      acid-labile pathogenic bacteria which then may be aspirated. A secondary
      postulate is that PPIs, through their inhibition of extra-gastric H(+)/K(+)
      ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus
      resulting in increased bacterial colonization of the larynx, esophagus and lungs.
      To date, several retrospective case control studies have been published looking
      at the association between PPI use and CAP. Some studies found a temporal
      relationship between PPI exposure and the incidence of pneumonia, but only two
      could define a dose-response relationship. Furthermore, other studies found an
      inverse correlation between duration of PPI use and risk of CAP. In terms of HAP,
      we reviewed two retrospective cohort studies and one prospective study. One
      retrospective study in a medical ICU found no increased association of HAP in PPI
      exposed patients compared to no acid-lowering therapy, while the other in
      cardiothoracic surgery patients showed a markedly increased risk compared to
      those receiving H(2)RAs. The one prospective study in ICU patients showed an
      increased risk of HAP with PPIs, but not with H(2)RAs. In conclusion, the current
      literature shows a slight trend toward an association between PPI use and
      pneumonia and an increased risk with PPIs over H(2)RAs, but the findings are not
      consistent across all studies. Larger controlled trials still need to be done to
      better identify the risk that PPIs impart towards patients contracting CAP or
      HAP. Until these are completed, we will have to continue to extrapolate across
      smaller controlled trials to predict the associated risks in our respective
      patient populations. In the interim, it appears prudent to limit the use of PPIs
      to situations where they are clinically indicated and, in such cases, use them at
      the lowest effective dose. In the case of prescribing for stress ulcer
      prophylaxis in ICU patients, perhaps H(2)RAs should be used as the preferred
      agents over PPIs.

PMID- 21731914
TI  - Hospitalist Rounds: nausea, fever, and weight loss.
AB  - The patient's monospot test was positive, but the clinical picture didn't fully
      match infectious mononucleosis. We dug further.

PMID- 21731915
TI  - Rethinking our approach to refills.

PMID- 21731916
TI  - Hyperthyroidism: a stepwise approach to management.
AB  - Clinical presentation and an algorithm-guided laboratory assessment can quickly
      narrow the diagnosis and help direct your choice, timing, and sequence of
      treatments.

PMID- 21731917
TI  - Looking beyond the D-dimer.
AB  - The D-dimer test ruled out a pulmonary embolism in our patient, but her signs and
      symptoms suggested that we take another look.

PMID- 21731918
TI  - Did too much Wii cause your patient's injury?
AB  - Motion-controlled game consoles like Wii may be used to play virtual sports, but
      the injuries associated with them are real. Here's what to watch for--and a handy
      table linking specific games to particular injuries.

PMID- 21731919
TI  - PURLs: consider this option for heavy menstrual bleeding.
AB  - Women who fail to respond to--or are unable to tolerate--other treatments for
      heavy menstrual blood loss now have another choice.

PMID- 21731920
TI  - CVD prevention in women: a practice update.
AB  - Which interventions should you consider recommending to women to reduce their
      risk of CVD? This comparison of the AHA's 2011 guidelines with USPSTF
      recommendations highlights the benefits of drawing upon both.

PMID- 21731921
TI  - Chronic lesions on legs.
AB  - The rash was asymptomatic and had developed over the past few years. The patient
      wasn't taking any prescriptions and hadn't changed detergents.

PMID- 21731922
TI  - Clinical Inquiry: which smoking cessation interventions work best?
AB  - Nicotine replacement therapy, bupropion, nortriptyline, clonidine, and
      varenicline are all effective, although insufficient evidence exists to recommend
      one intervention over another. Effective nonpharmacologic interventions include
      brief physician advice and more intensive counseling, such as proactive telephone
      counseling, group and individual counseling, and use of quit lines.

PMID- 21731923
TI  - Clinical Inquiry: is it safe to vaccinate children against varicella while
      they're in close contact with a pregnant woman?
AB  - Yes. All healthy children without evidence of immunity to varicella who are
      living in a household with a susceptible pregnant woman should be vaccinated.

PMID- 21731924
TI  - Cosmetic foot surgery: a step in the wrong direction.

PMID- 21731925
TI  - Can interepicondylar distance predict joint line position in primary and revision
      knee arthroplasty?
AB  - Restoration of the position of the prosthetic joint line (JL) to the same level
      as the original JL is a challenging problem in primary adn revision knee
      arthroplasty, and there is no reliable method for achieving this objective. We
      hypothesized that there is a constant ratio between the interepicondylar distance
      (IED) and the perpendicular distance from this interepicondylar line to the JL
      and analyzed 100 computed tomography scans of the knee to study this
      relationship. The IED and the perpendicular distance from this interepicondylar
      line to the JL was measured using both the clinical epicondylar axis (CEA) and
      the surgical epicondylar axis (SEA). Results showed that the ration between the
      IED adn the perpendicular distance from the interepicondylar line to the JL was
      3.0 using the CEA and 3.3 using the SEA. The ratio was found to be constant,
      irrespective of the patient's sex or height. We suggest using the CEA because of
      the ease in localizing epicondyle peaks and conclude that the position of the JL
      from the interepicondylar line is one-third the IED using the CEA. This will
      prove to be a valuable aid in restoring the JL position during knee arthroplasty.

PMID- 21731926
TI  - Associated lateral process and posteromedial tubercle talus fractures:a case
      report and literature review.
AB  - This article describes the case of a 39-year-old man who sustained both a lateral
      process and posteromedial tubercle talus fracture. Both fractures were treated
      with open reduction and internal fixation resulting in a satisfactory clinical
      outcome. Although this combination of injuries has been described in the
      literature, this is the first reported case to describe surgical fixation of both
      fractures.

PMID- 21731927
TI  - Women's musculoskeletal foot conditions exacerbated by shoe wear: an imaging
      perspective.
AB  - The predominance of several musculoskeletal foot conditions in women are largely
      the result of biomechanical alterations caused by ill-fitting shoes. In
      particular, the altered biomechanics (associated with high-heeled shoes and shoes
      with a narrowed toe box) has been linked to the genesis of hallux valgus, hammer
      toe deformity, Haglund syndrome, metatarsal stress fracture, Freiberg infraction,
      and Morton neuroma. In reviewing the imaging findings of several of these
      conditions, we emphasize the role of radiographs, special radiographic views, and
      the utility of more costly studies, such as magnetic resonance imaging.

PMID- 21731928
TI  - Diagnostics in suspicion of ankle syndesmotic injury.
AB  - Ankle sprains are among of the most common injuries seen in daily orthopaedic
      practice. Beside injuries of the lateral ligament, which is the most frequently
      injured single structure in the body of athletes, sprains can also affect the
      tibiofibular syndesmosis. These injuries are known as high ankle sprains. They
      can occur with or without a bony injury. In this report, we will discuss the high
      ankle sprain without any bony injury. These kinds of injuries are rare, but often
      associated with complications and are frequently misdiagnosed or undiagnosed. The
      purpose of this article is to provide a clear understanding of clinical tests
      described in the literature for testing of syndesmotic integrity.

PMID- 21731929
TI  - Use of intraoperative temporary invasive distraction to reduce a chronic talar
      neck fracture-dislocation.
AB  - Temporary invasive distraction can facilitate fracture reduction in the setting
      of delayed surgical intervention resulting in shortening and contracted soft
      tissues.

PMID- 21731930
TI  - Tibial stress injuries in athletes.

PMID- 21731931
TI  - Hiring technologically advanced staff.

PMID- 21731932
TI  - Improving function in transtibial amputation: the distal tibiofibular bone-bridge
      with Arthrex Tightrope fixation.
AB  - The distal tibiofibular bone bridge for transtibial amputation is designed to
      allow for axial loading in a prosthesis, better proprioception of the residual
      limb, and less pain from tibiofibular instability. Originally described as an
      osteoperiosteal sleeve by Janos Ertl, Sr. in the early 20th century, it was later
      modified by Pinto and Harris to a fibular bone block technique. In this article,
      we describe a new technique for securing the fibular bone block. Use of the
      Tightrope (Arthrex, Naples, Florida) suture-button fixation system minimizes the
      chance of symptomatic hardware, prevents diastasis, and allows physiologic
      micromotion. In our experience, this procedure has been highly successful.

PMID- 21731933
TI  - Compression force and pullout strength comparison of bioabsorbable implants for
      osteochondral lesion fixation.
AB  - We conducted a study to characterize compression forces and pullout strengths of
      4 commercially available bioabsorbable nails and screws in a synthetic bone
      model. A piezoelectric sensor was used to measure peak compression forces, and a
      material testing machine was used to measure maximum pullout strengths. The
      strongest compression force was found for SmartScrew (12.7 N), then SmartNail
      (12.3 N), LactoNail (8.5 N), and ReUnite Screw (5.1 N). Mean compression force
      was significantly (P<.05) different between LactoNail and SmartScrew, ReUnite
      Screw and SmartNail, and ReUnite Screw and SmartScrew. The most pullout strength
      was found for SmartScrew (530 N), then ReUnite Screw (414 N), SmartNail (336 N),
      and LactoNail (189 N). These values were all statistically significantly (P<.05)
      different from each other. In this model, SmartScrew had the overall strongest
      compression force and most pullout strength.

PMID- 21731934
TI  - Transradial radial perilunate: a case report.
AB  - We report a rare case of transradial styloid radial perilunate dislocation in a
      patient who presented with ulnar nerve symptoms, and we describe our treatment
      approach to this unusual injury. In a literature search, we found no other report
      of such an injury.

PMID- 21731935
TI  - Modified technique for unipolar allograft ankle replacement: midterm follow-up. A
      case report.
AB  - The management of tibiotalar arthritis remains a clinical challenge. Conventional
      treatment relies primarily upon arthrodesis or prosthetic arthroplasty. Fresh
      osteochondral total ankle allograft transplantation has been reported in limited
      cases. We report the case of a 42-year-old male who underwent a tibial
      refrigerated osteochondral allograft and a talar refrigerated osteochondral
      mosiacplasty. At 66-month follow-up, the patient demonstrated no limp with
      walking and was able to participate in tennis and snow skiing with no pain. His
      Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, total
      WOMAC score, and American Orthopaedic Foot and Ankle Society (AOFAS) Ankle
      Hindfoot Scale score were 0, 94, and 98, respectively. The final radiograph
      showed complete integration of the allograft with mild joint space narrowing.
      Osteochondral allografting for ankle arthritis may be considered an option in
      select patients.

PMID- 21731936
TI  - Studies of the isomerization and photophysical properties of a novel 2,2':6',2''
      terpyridine-based ligand and its complexes.
AB  - A novel 2,2':6',2''-terpyridine-based ligand L and its complexes
      [ML(2)](ClO(4))(2).CH(2)Cl(2) (M = Cd 1, Zn 2, Cu 4, Mn 5), [CoL(2)](ClO(4))(2)3,
      CdLI(2)6 and CdL(SCN)(2)7 were synthesized and fully characterized. The crystal
      structures of 1-6 were solved by single crystal X-ray diffraction analysis. The
      linear absorption and emission properties, and third-order nonlinear optical
      (NLO) properties of all the complexes were systematically investigated. The
      equilibrium of the trans- and cis- isomers of L was studied both experimentally
      and theoretically. The configurations and photophysical properties of the
      complexes display a large dependence on the choice of metal ions and anions.

PMID- 21731937
TI  - SCS-pincer palladium-catalyzed auto-tandem catalysis using dendritic catalysts in
      semi-permeable compartments.
AB  - Novel monometallic and dendritic SCS-pincer palladium complexes 2, 3 and 4 have
      been synthesized in good yields (60-89%) and high purity (palladium loading
      >97%). These complexes were successfully used as catalysts in the stannylation of
      cinnamyl chloride with hexamethylditin and in the catalytic auto-tandem reaction
      consisting of this stannylation followed by an electrophilic addition with 4
      nitrobenzaldehyde, showing similar reaction rates and selectivities for all
      complexes. Dendritic complex 4 has furthermore been used in the compartmentalized
      catalysis of single and auto-tandem reactions, allowing catalyst reuse for four
      consecutive runs.

PMID- 21731938
TI  - Protein assemblies by site-specific avidin-biotin interactions.
AB  - Exploiting self-assembly systems with biological building blocks is of
      significant interest in the fabrication of advanced biomaterials. We assessed the
      potential use of site-specific ligand labeling of protein building blocks in
      designing functional protein self-assemblies by combining site-specifically
      biotinylated bacterial alkaline phosphatase (as a bidentate or tetradentate
      ligand unit) and streptavidin (as a tetrameric receptor).

PMID- 21731939
TI  - A new rhodamine based colorimetric 'off-on' fluorescence sensor selective for
      Pd2+ along with the first bound X-ray crystal structure.
AB  - A new fluorescence rhodamine derivative bearing an 8-aminoquinoline moiety has
      been designed and synthesized for selective sensing of Pd(2+) in the presence of
      other competing metal ions in aqueous media. Pd(2+) induced spirolactam ring
      opening of rhodamine is confirmed for the first time by the X-ray crystal
      structure of the bound Pd(2+)-complex.

PMID- 21731940
TI  - Behaviors of dissolved antimony in the Yangtze River Estuary and its adjacent
      waters.
AB  - Antimony is a naturally occurring and cumulatively toxic element. With increasing
      concern as an inorganic contaminant, research on its environmental behavior is
      becoming a necessity. However, very little is known about this element. To
      further understand its biogeochemical behaviors and roles in the ecosystem, the
      main species of dissolved inorganic antimony (Sb(iii) and Sb(v)) in Yangtze River
      Estuary and its adjacent waters were determined by hydride generation and atomic
      fluorescence (HG-AFS) in our study. Results show that in surface water, the
      concentration for Sb(iii) and Sb(v) were in the range 0.029 MUg L(-1)~ 0.736 MUg
      L(-1) and 0.121 MUg L(-1)~ 2.567 MUg L(-1), with averages of 0.152 MUg L(-1) and
      0.592 MUg L(-1), respectively. While concentrations of Sb(iii) and Sb(v) in the
      bottom layer were much lower, ranging from 0.023 MUg L(-1) to 0.116 MUg L(-1)
      (average of 0.050 MUg L(-1)) and from 0.047 MUg L(-1) to 0.441 MUg L(-1) (average
      of 0.194 MUg L(-1)), respectively. Data analysis further demonstrates that the
      major processes controlling antimony geochemistry in the area are riverine input,
      atmospheric deposition, incursion of Taiwan Warm Current, and release from
      particulate phase. The surface-enrichment and bottom-depletion depth profile
      reveals it does appear as a mildly scavenged element but is less like arsenic
      than previously believed. Sb(v) was the predominant speciation in aquatic
      environment of our research, and Sb(iii) was a minor constituent of the total
      antimony. Regarding the adsorption-desorption process onto SPM, Sb(iii) has a
      higher affinity to particulate phase than Sb(v). Furthermore, the significant
      correlation between antimony and nutrients indicates it is an element with great
      biological potential, which is also an important behavior for antimony.

PMID- 21731941
TI  - Piperazic acid-containing natural products: isolation, biological relevance and
      total synthesis.
AB  - Since their first discovery in 1959, natural products containing the piperazic
      acid motif have been isolated from a variety of sources and exhibit diverse
      biological activity profiles. This review provides information about their
      isolation and biological activities, and presents an overview of recent total
      syntheses of these molecules.

PMID- 21731946
TI  - pH-programmable DNAzyme nanostructures.
AB  - Two engineered DNA nanostructures consisting of a nucleic acid functional hairpin
      and a DNA "tweezers" assembly act as pH-switchable devices for the "ON-OFF"
      activation/deactivation of the horseradish-peroxidase-mimicking DNAzyme.

PMID- 21731947
TI  - Anatomy of the S(1D) + H2 reaction: the dynamics on two new potential energy
      surfaces from quantum dynamics calculations.
AB  - We present exact quantum integral and differential cross sections for the title
      reaction from a time-dependent wavepacket method which takes account of all
      Coriolis couplings. We employ two new potential energy surfaces fitted using the
      double many-body expansion (DMBE) method. The difference between the two surfaces
      is that for the first the data was extrapolated to the complete basis set limit
      (CBS) and for the second the data was corrected semi-empirically (SEC). While the
      DMBE/CBS surface is, on first impressions, regarded as the most accurate, our
      results show that this surface gives consistent smaller cross section when
      compared to previous results employing an earlier surface, named Ho after its
      first author. We also find that the DMBE/CBS surface features an unphysical
      barrier for contracted H(2) distances which explains the smaller results. The
      DMBE/SEC surface, which is based on the same data, does not show the same barrier
      and the results compare much better to previous theoretical results as well as
      those from experiment. While we find that overall the differential cross sections
      from the DMBE/SEC surface are forward scattered, which is in line with
      experiment, the cross sections do not rise steeply enough with decreasing energy
      showing that this surface is not sufficiently attractive at low energies. We find
      this is due to a shallow van der Waals well present for the Ho surface but not on
      the DMBE surfaces.

PMID- 21731948
TI  - Size dependences of the diradical character and the second hyperpolarizabilities
      in dicyclopenta-fused acenes: relationships with their
      aromaticity/antiaromaticity.
AB  - Using long-range corrected density functional theory, the relationships between
      the electronic, magnetic, and nonlinear optical properties are drawn for two
      families of organic compounds, the dicyclopenta-fused acenes (DPAs) and the
      polyacenes (PAs), containing up to N = 12 fused rings. First, the longitudinal
      second hyperpolarizability (gamma) of singlet DPAs is significantly enhanced with
      increasing system size, in comparison to PAs. This behavior is associated with an
      increase in the longitudinal spin polarization between the terminal five-membered
      rings of DPAs and is consistent with previous studies where gamma is maximized
      for intermediate diradical character. The size dependence of the diradical
      character is also found to cause a hump in the gamma/N evolution for singlet DPAs
      around N = 8. In fact, in the case of singlet PAs, the diradical characters y(0)
      and y(1), the various magnetic properties and the gamma/N values vary
      monotonically with N, whereas for singlet DPAs, the shielding, the
      magnetizability, and the gamma/N values exhibit extrema near N = 8 due to the
      appearance of transversal spin polarization in the middle six-membered rings in
      addition to the longitudinal spin polarization between the terminal five-membered
      rings. Moreover, it is shown that for singlet DPAs the longitudinal spin
      polarization (characterized by y(0)) is associated with the antiaromaticity (N <=
      3) and the slight- or non-aromaticity (N >= 4) of the terminal five-membered
      rings, whereas the appearance of transversal spin-polarization (characterized by
      y(1)) is associated with the decrease in the aromaticity in the inner six
      membered rings as shown for large PAs. Therefore, the exceptional behaviors in
      singlet DPAs for small N (N < 9) are caused by the increase in diradical
      character y(0) correlated with the anti-aromaticity or the slight-/non
      aromaticity of terminal rings and the corresponding emergence of a global
      aromatic character. Such a relationship between the aromaticity/antiaromaticity
      and the diradical character is useful for designing real open-shell NLO molecules
      through the control of their diradical characters.

PMID- 21731949
TI  - Modulating the immobilization process of Au nanoparticles on TiO2(110) by
      electrostatic interaction between the surface and ionic liquids.
AB  - We found that the adsorption states of Au nanoparticles (NPs) on TiO(2)(110)
      varied with the ionic liquids (ILs) that encapsulate the NPs during the entire
      process from synthesis of NPs to immobilization of the NPs on the surface at 323
      K. Five kinds of ILs, including three 1-butyl-3-methylimidazolium ([C(4)MIm])
      cation-based ILs of tetrafluoroborate ([C(4)MIm][BF(4)]), hexafluorophosphate
      ([C(4)MIm][PF(6)]) and bis(trifluoromethylsulfonyl)amide ([C(4)MIm][NTf(2)]), and
      two [BF(4)] anion-based ILs of 1-(methoxymethyl)-1-methylpyrrolidinium
      ([PY1,1O1][BF(4)]) and N,N-diethyl-N-methyl-N-(2-methoxyethyl) ammonium
      ([N122,1O2][BF(4)]), were used. They provided different adsorption states of the
      Au NPs on the surface. We considered the determinant factor for the adsorption
      states of NPs on the surface from the viewpoint of electrostatic interactions
      between IL and IL and between IL and the surface. We deduced the influence of
      these interactions from the increments of NP's diameter and the amount of NPs
      after the immobilization, and obtained the order of anions as [BF(4)] ~ [NTf(2)]
      > [PF(6)] for the three [C(4)MIm] based ILs and the order of cations as [PY1,1O1]
      > [C(4)MIm] > [N122,1O2] for the three [BF(4)] based ILs. Interestingly, the
      above orders were no match with the conventional physicochemical and chemical
      parameters but beta of Kamlet-Taft solvent descriptors and Lewis basicity of
      anions in the case of anions of ILs. The results of anions indicate that the
      chemical natures of ILs might affect the immobilization of NPs through hydrogen
      bonding or coordination bonding with the surface. We suggested that such a trend
      in anions was 'local viscosity' of ILs in the vicinity of surface. Besides, layer
      formation of IL on the surface might be also an influential factor to control the
      size of NPs and the surface density of NPs. Our results show that the combination
      of a charged surface and charged molecules has the potential for controlling
      locations of the NPs on the surface preferentially with tuning the electrostatic
      interaction.

PMID- 21731950
TI  - On the formation of anisotropic gold nanoparticles by sputtering onto a nitrile
      functionalised ionic liquid.
AB  - Sputtering deposition of gold onto the 1-(butyronitrile)-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide (BCN)MI.N(Tf)(2) ionic liquid (IL) has
      generated colloidal and stable gold nanospheres (AuNS) and gold nanodisks (AuND)
      in a bimodal size distribution. Upon increasing the sputtering discharge voltage,
      three distinct phenomena were observed: (i) the mean diameter of both AuNS and
      AuND decreased; (ii) the population with lower diameters increased and (iii) the
      formation of AuND disappeared at voltages higher than 340 V. By dissolving the
      colloidal gold nanoparticles (AuNPs) in isopropanol and dropping the product onto
      carbon-coated Cu grids, 2D and 3D superlattices tended to be formed, as observed
      by transmission electron microscopy (TEM). Therefore, the formation of AuND is
      probably related to a strong interaction between sputtered Au atoms of low
      kinetic energy and the nitrile groups orientated to the vacuum phase of the IL
      surface, which drives the preferential anisotropic lateral growth.

PMID- 21731951
TI  - Ionic liquids as recycling solvents for the synthesis of magnetic nanoparticles.
AB  - This work describes an easy synthesis (one pot) of MFe(2)O(4) (M = Co, Fe, Mn,
      and Ni) magnetic nanoparticles MNPs by the thermal decomposition of
      Fe(Acac)(3)/M(Acac)(2) by using BMI.NTf(2) (1-n-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide) or BMI.PF(6) (1-n-butyl-3-methylimidazolium
      hexafluorophosphate) ionic liquids (ILs) as recycling solvents and oleylamine as
      the reducing and surface modifier agent. The effects of reaction temperature and
      reaction time on the features of the magnetic nanomaterials (size and magnetic
      properties) were investigated. The growth of the MNPs is easily controlled in the
      IL by adjusting the reaction temperature and time, as inferred from Fe(3)O(4)
      MNPs obtained at 150  degrees C, 200  degrees C and 250  degrees C with mean
      diameters of 8, 10 and 15 nm, respectively. However, the thermal decomposition of
      Fe(Acac)(3) performed in a conventional high boiling point solvent (diphenyl
      ether, bp 259  degrees C), under a similar Fe to oleylamine molar ratio used in
      the IL synthesis, does not follow the same growth mechanism and rendered only
      smaller NPs of 5 nm mean diameter. All MNPs are covered by at least one monolayer
      of oleylamine making them readily dispersible in non-polar solvents. Besides the
      influence on the nanoparticles growth, which is important for the preparation of
      highly crystalline MNPs, the IL was easily recycled and has been used in at least
      20 successive syntheses.

PMID- 21731952
TI  - Four [Tp*W(MU3-S)3Cu3(MU3-Br)]-based clusters: synthesis, structural
      characterization and third-order NLO properties.
AB  - Treatment of [Et(4)N][Tp*W(MU(3)-S)(3)(CuBr)(3)] (Tp* = hydridotris(3,5
      dimethylpyrazol-1-yl)borate) (1) with an excess of alpha-methylpyridine (alpha
      MePy) and NH(4)PF(6) in CH(2)Cl(2) afforded a cationic cluster [Tp*W(MU(3)
      S)(3)Cu(3)(alpha-MePy)(3)(MU(3)-Br)](PF(6)) (2) while the reaction of 1 with an
      excess of 1,4-pyrazine (1,4-pyz) and NH(4)PF(6) in MeCN-CH(2)Cl(2) at 65  degrees
      C produced a polymeric cluster [Tp*W(MU(3)-S)(3)Cu(3)(1,4-pyz)((1,4
      pyz)(0.5))(2)(MU(3)-Br)][Tp*W(MU(3)-S)(3)(CuBr)(3)] (3). Reactions of 1 with
      melamine (MA) in 1:1 or 1:2 gave rise to another polymeric cluster [{Tp*W(MU(3)
      S)(3)Cu(3)Br(MU(3)-Br)}(2)(MA)(2)] (4) and a neutral cluster [Tp*W(MU(3)
      S)(3)Cu(3)Br(MU(3)-Br)(MA)(2)] (5), respectively. Compounds 2-5 were
      characterized by elemental analysis, IR spectra, UV-vis spectra, (1)H NMR,
      electrospray ionization (ESI) mass spectra and X-ray crystallography. The cation
      of 2 has a cubane-like [Tp*W(MU(3)-S)(3)Cu(3)(MU(3)-Br)] structure with each
      alpha-MePy ligand coordinated at one Cu(i) center. For 3, each [Tp*W(MU(3)
      S)(3)Cu(3)(MU(3)-Br)] core is interconnected by 1,4-pyz bridges to form a 1D
      cationic zigzag chain with the [Tp*W(MU(3)-S)(3)(CuBr)(3)](-) anions arranged
      along its two sides. For 4, each [Tp*W(MU(3)-S)(3)Cu(3)(MU(3)-Br)] core is
      interlinked by MA bridges to afford a 1D spiral chain. 5 adopts a cubane-like
      [Tp*W(MU(3)-S)(3)Cu(3)(MU(3)-Br)] structure in which one terminal Br and two MA
      ligands are coordinated at three Cu centers. The third-order nonlinear optical
      (NLO) properties of 1-5 in DMF were investigated by femtosecond degenerate four
      wave mixing (DFWM) technique with a 80 fs pulse width at 800 nm. Compounds 1-5
      exhibit good NLO responses, and 3 and 4 possess the largest second-order
      hyperpolarizability gamma values among the known W/Cu/S clusters bearing the
      [Tp*WS(3)] unit.

PMID- 21731954
TI  - Secretory pathway genes assessed by high-throughput microscopy and synthetic
      genetic array analysis.
AB  - We developed a procedure for automated confocal microscopy to image the effect of
      the non-essential yeast gene deletion set on the localisation of the plasma
      membrane GFP-labelled protein Mrh1p-GFP. To achieve this it was necessary to
      devise an expression system expressing Redstar2 RFP-fluorescence specifically in
      the nucleus, mCherry RFP at a lower intensity in the cytoplasm and Mrh1p-GFP in
      the plasma membrane. This fluorescence labelling scheme utilising specifically
      designed image analysis scripts allowed automated segmentation of the cells into
      sub-regions comprising nuclei, cytoplasm and cell-surface. From this high
      throughput high content screening approach we were able to determine that gene
      deletions including emc1Delta, emc2Delta, emc3Delta, emc4Delta, emc5Delta and
      emc6Delta, caused intracellular mislocalisation at the ER of a plasma membrane
      protein Mrh1p-GFP. CPY processing patterns were unaffected in these mutants and
      collectively our data suggest a transport role for the EMC genes within the early
      secretory pathway. HAC1 is central to the unfolded protein response (UPR) and in
      its absence, i.e. the absence of UPR, emc1Delta-, emc3Delta-, emc4Delta-,
      emc5Delta-hac1Delta double mutants were specifically hypersensitive to ER-stress
      (tunicamycin) lending credence to the usefulness of the high content microscope
      screening for discovery of functional effects of single mutants.

PMID- 21731955
TI  - PELDOR analysis of enzyme-induced structural changes in damaged DNA duplexes.
AB  - PELDOR (pulsed electron-electron double resonance) spectroscopy was applied to
      determine spin-spin distances in spin-labeled DNA duplexes (13-mer and 17-mer)
      containing the damaged sites 8-oxoguanine or uncleavable abasic site analogue
      tetrahydrofuran. The lesions were located in one strand of the DNA, and two
      nitroxyl spin labels were attached at the 5'- and 3'-ends of the complementary
      strand. PELDOR data allow us to obtain distances between the two spin labels in
      DNAs, which turned out to be around 5 nm for the 13-mer DNA and around 6 nm for
      17-mer DNA. Results of PELDOR measurements were supported by molecular dynamics
      calculations. Study of the interaction of DNA fragments with DNA repair enzyme 8
      oxoguanine-DNA glycosylase from E. coli (Fpg protein) showed that this
      interaction leads to a noticeable decrease of the distance between spin labels,
      which indicates the enzyme-induced bending of the DNA duplex. This bending may be
      important for the mechanisms of recognition of damaged sites by DNA repair
      enzymes.

PMID- 21731956
TI  - N-Heterocyclic carbene (NHC) ligands and palladium in homogeneous cross-coupling
      catalysis: a perfect union.
AB  - Cross-coupling reactions using Pd-NHC (NHC = N-heterocyclic carbene) catalysts
      are discussed in this critical review and examined in terms of catalytic activity
      and how these have permitted advances in the area as they developed (95
      references).

PMID- 21731957
TI  - From Cerius2 based stereoview to mouse and enzyme: the model systems for
      discovery of novel urokinase inhibitors.
AB  - Antifibrinolytic therapy during major complex surgery could reduce blood loss and
      allogeneic transfusion. Novel antagonists of the plasminogen activator and the
      corresponding model system are of clinical importance. In this paper (1S,2'S,3S)
      1-[2-(S)-carboxylindolemethylenemethineaminoeth-1-yl]-2,3,4,5
      tetrahydropyrolo[1,2:1,6]pyrazino[3,4:2,3]-1,2,3,4-tetrahydrocarboline-2,5-dione
      (CIPPC) was presented as a novel antagonist of plasminogen activator, and its
      blood coagulation and action mechanism were investigated by using a model system
      which consisted of a mouse-tail bleeding assay, in vitro and in vivo fibrinolysis
      inhibition assays, a thrombus formation assay and a plasminogen (PLG)
      electrophoresis assay.

PMID- 21731958
TI  - Photophysical, electrochemical and anion sensing properties of Ru(II) bipyridine
      complexes with 2,2'-biimidazole-like ligand.
AB  - A new anion sensor [Ru(bpy)(2)(DMBbimH(2))](PF(6))(2) (3) (bpy is 2, 2'
      bipyridine and DMBbimH(2) is 7,7'-dimethyl-2,2'-bibenzimidazole) has been
      developed. Its photophysical, electrochemical and anion sensing properties are
      compared with two previously investigated systems,
      [Ru(bpy)(2)(BiimH(2))](PF(6))(2) (1) and [Ru(bpy)(2)(BbimH(2))](PF(6))(2) (2)
      (BiimH(2) is 2,2'-biimidazole and BbimH(2) is 2,2'-bibenzimidazole). The high
      acidity of the N-H fragments in these complexes make them easy to be deprotonated
      by strong basic anions such as F(-) and OAc(-), and they form N-H...X hydrogen
      bonds with weak basic anions like Cl(-), Br(-), I(-), NO(3)(-), and HSO(4)(-).
      Complex 3 displays strong hydrogen bonding with these 5 weak basic anions, with
      binding constants between 17,000 and 21,000, which are larger than those observed
      in complex 1, with binding constants between 3300 and 5700, and in complex 2,
      which shows no hydrogen bonding toward Cl(-), Br(-), I(-), and NO(3)(-), and
      forms considerable hydrogen bonds with HSO(4)(-) with a binding constant of
      11,209. These hydrogen bonding behaviours give different NMR, emission and
      electrochemical responses. The different anion binding affinity of these
      complexes may be mainly attributed to their different pK(a1) values, 7.2 for 1,
      5.7 for 2, and 6.2 for 3. The additional methyl groups at the 7 and 7' positions
      of complex 3 may also play an important role in the enhancement of anion binding
      strength.

PMID- 21731959
TI  - Transition metal-catalysed cross-coupling reactions of P-activated enols.
AB  - Transition metal catalysed cross-coupling reactions are ubiquitous in organic
      chemistry providing an impressive technique for C-C bond formation. Whilst many
      electrophilic partners have been described for these reactions, aryl and vinyl
      phosphates, phosphonates and phosphonites can offer advantages in terms of
      preparation, stability and reactivity profile. This critical review summarises
      the advances made to date utilising P-activated enols in metal-catalysed cross
      coupling reactions (97 references).

PMID- 21731960
TI  - Recent advances in enantioselective organocatalyzed anhydride desymmetrization
      and its application to the synthesis of valuable enantiopure compounds.
AB  - Recent years have witnessed increasing interest in the field of asymmetric
      organocatalysis. In particular, efforts in this field have been devoted to the
      use of small organic molecules in asymmetric processes based on enantiotopic face
      discrimination and, only recently, efforts have also been devoted to asymmetric
      organocatalytic desymmetrization of prochiral substrates-a process based on
      enantiotopic group discrimination. This critical review documents the advances in
      the use of organocatalysis for the enantioselective desymmetrization of achiral
      and meso anhydrides and its application to the synthesis of valuable compounds as
      reported until 2010 (134 references).

PMID- 21731961
TI  - Electrochemiluminescence analysis of folate receptors on cell membrane with on
      chip bipolar electrode.
AB  - In this paper we report a transparent bipolar electrode based microfluidic chip
      electrochemiluminescence (ECL) system for sensitive detection of folate receptors
      (FR) on cell membranes. This integrated system consists of a
      poly(dimethylsiloxane) (PDMS) layer containing a microchannel and a glass bottom
      sheet with indium tin oxide (ITO) strips as bipolar detectors. The ITO strips are
      fabricated using a PDMS micromold with carbon ink as a protective layer in place
      of traditional photoresist. The configuration of the bipolar electrode has great
      influence on the ECL intensity of Ru(bpy)(3)(2+)/tripropylamine(TPA) system.
      Further studies show that folic acid (FA) can strongly inhibit the ECL of the
      Ru(bpy)(3)(2+)/TPA system. Based on specific recognition between FA and FR on
      cell membrane, this microfluidic chip-ECL system is successfully applied for
      detecting the level of FR on human cervical tumor (HL-60) cells and MEF cells. It
      is found that the ECL intensity increases with the number of HL-60 cells in the
      range of 21 to 3.28 * 10(4) cells/mL. The average level of FR on HL-60 cells is
      calculated to be 8.05 +/- 0.75 * 10(-18) mol/cell. While for MEF cells, it shows
      a much slower ECL increment than HL-60 cells due to the much lower FR level on
      MEF cells (5.30 +/- 0.61 * 10(-19) mol/cell). Moreover, exocytosis of FA after FR
      mediated endocytosis was observed according to the change of the ECL signal with
      the incubation time of HL-60 cells in the FA- Ru(bpy)(3)(2+)/TPA system.

PMID- 21731962
TI  - Sensitive triplet exciton detection in polyfluorene using Pd-coordinated
      porphyrin.
AB  - We developed a sensitive spectroscopic method to probe triplet concentration in
      thin films of polyfluorene (PF) at room temperature. The energy of photoexcited
      triplet excitons is transferred to the guest metal-organic complex, meso
      tetratolylporphyrin-Pd (PdTPP), and detected as phosphorescent emission. The
      phosphorescence intensity of PdTPP-PF blends is proportional to the independently
      measured triplet concentration using photoinduced absorption experiments. The
      high sensitivity of this method allows room temperature detection of triplet
      excitons in spin-coated polymer films as thin as 10 nm. We found that the triplet
      lifetime is independent of PdTPP concentration and therefore this method is
      nearly non-perturbing for the triplet population.

PMID- 21731963
TI  - Nanoparticle-coated separators for lithium-ion batteries with advanced
      electrochemical performance.
AB  - We report a simple, scalable approach to improve the interfacial characteristics
      and, thereby, the performance of commonly used polyolefin based battery
      separators. The nanoparticle-coated separators are synthesized by first plasma
      treating the membrane in oxygen to create surface anchoring groups followed by
      immersion into a dispersion of positively charged SiO(2) nanoparticles. The
      process leads to nanoparticles electrostatically adsorbed not only onto the
      exterior of the surface but also inside the pores of the membrane. The thickness
      and depth of the coatings can be fine-tuned by controlling the zeta-potential of
      the nanoparticles. The membranes show improved wetting to common battery
      electrolytes such as propylene carbonate. Cells based on the nanoparticle-coated
      membranes are operable even in a simple mixture of EC/PC. In contrast, an
      identical cell based on the pristine, untreated membrane fails to be charged even
      after addition of a surfactant to improve electrolyte wetting. When evaluated in
      a Li-ion cell using an EC/PC/DEC/VC electrolyte mixture, the nanoparticle-coated
      separator retains 92% of its charge capacity after 100 cycles compared to 80 and
      77% for the plasma only treated and pristine membrane, respectively.

PMID- 21731964
TI  - Migration of As, Hg, Pb, and Zn in arroyo sediments from a semiarid coastal
      system influenced by the abandoned gold mining district at El Triunfo, Baja
      California Sur, Mexico.
AB  - Extensive waste deposits (tailings) and ash from the ignition oven of the
      abandoned gold mine of mining district El Triunfo (MD-ET) in Baja California Sur,
      Mexico have released trace elements into the sediments of the Hondo-Las Gallinas
      El Carrizal arroyo, which connects to the Pacific Ocean through an evaporitic
      basin. Migration of these elements through the arroyo is mainly caused by winds
      or tropical hurricanes that occur sporadically during the summer and cause the
      otherwise dry arroyo to overflow. To evaluate the concentration and distribution
      of the elements As, Hg, Pb, and Zn along the 48 km arroyo, surface sediments were
      collected from 26 sites, ranging from close to the MD-ET to the mouth of the
      arroyo at the Pacific Ocean. Concentrations in tailings and ash were for As 8890
      and 505 000 mg kg(-1); for Hg 0.336 and 54.9 mg kg(-1); for Pb 92,700 and 19,300
      mg kg(-1); and for Zn 49,600 and 1380 mg kg(-1). The average of the Normalized
      Enrichment Factor (Av-NEF) in surface sediments, calculated using background
      levels, indicates that the sediments are severely contaminated with As and Zn (Av
      NEF = 22), Pb (Av-NEF = 24) and with a moderate contamination of Hg (Av-NEF =
      7.5). The anthropogenic influence of those elements is reflected in the arroyo
      sediments as far as 18 km away from the MD-ET, whereas the samples closest to the
      discharge into the Pacific Ocean show a natural to moderate enrichment for As and
      Zn and low or no enrichment for Hg and Pb. A principal components analysis
      identified four principal components that explained 90% of the total variance.
      Factor 1 was characterized by a high positive contribution of the anthropogenic
      source elements, especially As, Pb, and Zn (37%), whereas Factor 2 was strongly
      correlated with the oxy-hydroxides of Fe and Mn (27%). Factor 3 was correlated
      with Li (16%) and Factor 4 with Al (10%), which indicates more than one source of
      lithogenic composition, though they played a minor role in the distribution of
      the elements.

PMID- 21731965
TI  - Uptake and distribution of ceria nanoparticles in cucumber plants.
AB  - The presence and release of nanoparticles (NPs) into the environment have
      important implications for human health and the environment. A critical aspect of
      the risk assessment of nanoparticles is to understand the interactions of
      manufactured nanoparticles with plants. In this study, the uptake and
      distribution characteristics of two types of ceria nanoparticles with sizes of
      ca. 7 nm and 25 nm in cucumber plants were investigated using a radiotracer
      method and other techniques. With increasing concentration of the nanoparticles,
      concentration dependent absorption by the plant roots was noticed, but the
      majority of the particles only loosely adhered to the root surface. The seedlings
      treated with 7 nm ceria particles showed significantly higher ceria contents in
      both roots and shoots than those exposed to 25 nm ceria particles at all test
      concentrations (2, 20, and 200 mg L(-1)). Only very limited amounts of ceria
      nanoparticles could be transferred from the roots to shoots because the entry of
      nanoparticles into the roots was difficult. However, the results of tissue
      distributions of ceria nanoparticles in the plants and two dimensional
      distributions of the particles in the leaves imply that once they have entered
      into the vascular cylinder, ceria nanoparticles could move smoothly to the end of
      the vascular bundle along with water flow. To the best of our knowledge, this is
      the first detailed study of uptake and distribution of metal oxide nanoparticles
      in plants.

PMID- 21731966
TI  - [The death of Dr. Mariano J. Levin].

PMID- 21731967
TI  - [Non-O1, non-O139 Vibrio cholerae bacteremia in a chronic hemodialysis patient].
AB  - Non-O1, and non-O139 Vibrio cholerae is an infrequent cause of bacteremia. There
      are no reports of such bacteremia in chronic hemodialysis patients. This work
      describes the case of a chronic hemodialysis patient that had an episode of
      septicemia associated with dialysis. Blood cultures were obtained and treatment
      was begun with vancomycin and ceftazidime. After 6.5 hours of incubation in the
      Bact/Alert system there is evidence of gram-negative curved bacilli that were
      identified as Vibrio cholerae by conventional biochemical tests, API 20 NE and
      the VITEK 2 system. This microorganism was sent to the reference laboratory for
      evaluation of serogroup and virulence factors and was identified as belonging to
      the non-O1 and non-O139 serogroup. The cholera toxin, colonization factor and
      heat-stable toxin were not detected. The isolate was susceptible to ampicillin,
      trimethoprim-sulfamethoxazole, ciprofloxacin, tetracycline, ceftazidime and
      cefotaxime by the disk diffusion method and the VITEK 2 system. The patient
      received intravenous ceftazidime for a 14 day- period and had a favorable
      outcome.

PMID- 21731968
TI  - First report of Israeli acute paralysis virus in asymptomatic hives of Argentina.
AB  - Honey bee mortality has recently been associated with Israeli acute paralysis
      virus (IAPV), a proposed etiological agent for a new syndrome known as Colony
      Collapse Disorder. Bees infected with this virus show shivering wings, progress
      into paralysis, and finally die outside the hive. During the last years, honey
      bee mortality became a serious problem for Argentinean beekeepers. We herein
      report the preliminary results of a survey carried out to detect IAPV in samples
      taken from several Argentine provinces, by using a reverse transcription
      Polymerase Chain Reaction assay. Our data indicate the existence of high
      frequency of IAPV in asymptomatic hives of Argentina.

PMID- 21731969
TI  - [Soil texture as a regulating factor of Escherichia coli adsorption in a Rolling
      Pampa basin (Argentina)].
AB  - Increase of bovine livestock rates in fragile areas of the Rolling Pampa entails
      a high risk of biological contamination. This biological contamination is
      regulated by edaphic variables such as texture, which control biological
      contaminants transport towards water bodies. In this work bacterial adsorption
      was correlated with individual particle sizes in 27 soils of a typical basin of
      the Rolling Pampa with slow centrifugation techniques. Bacterial adsorption
      values, using E. coli (ATCC 8739), ranged between 25.3 and 73.3% and significant
      correlation (R2 = 0.6) was found between bacterial adsorption and clay content.
      This correlation was improved when particles smaller than 3 um were considered
      (R2 = 0.64) highlighting the capacity of very fine silt in adsorption mechanisms.
      Data obtained were compared with those proposed by Ling et al. (2002), finding
      similar slope but different intercept. This difference disappeared when a wild
      strain, isolated from bovine manures present in the basin, was used, since a
      bacterial adsorption increase of 48% was found.

PMID- 21731970
TI  - Exploring the Antarctic soil metagenome as a source of novel cold-adapted enzymes
      and genetic mobile elements.
AB  - Metagenomic library PP1 was obtained from Antarctic soil samples. Both functional
      and genotypic metagenomic screening were used for the isolation of novel cold
      adapted enzymes with potential applications, and for the detection of genetic
      elements associated with gene mobilization, respectively. Fourteen
      lipase/esterase-, 14 amylase-, 3 protease-, and 11 cellulase-producing clones
      were detected by activity-driven screening, with apparent maximum activities
      around 35  degrees C for both amylolytic and lipolytic enzymes, and 35-55 
      degrees C for cellulases, as observed for other cold-adapted enzymes. However,
      the behavior of at least one of the studied cellulases is more compatible to that
      observed for mesophilic enzymes. These enzymes are usually still active at
      temperatures above 60  degrees C, probably resulting in a psychrotolerant
      behavior in Antarctic soils. Metagenomics allows to access novel genes encoding
      for enzymatic and biophysic properties from almost every environment with
      potential benefits for biotechnological and industrial applications. Only intI-
      and tnp-like genes were detected by PCR, encoding for proteins with 58-86 %, and
      58-73 % amino acid identity with known entries, respectively. Two clones, BAC 27A
      9 and BAC 14A-5, seem to present unique syntenic organizations, suggesting the
      occurrence of gene rearrangements that were probably due to evolutionary
      divergences within the genus or facilitated by the association with transposable
      elements. The evidence for genetic elements related to recruitment and
      mobilization of genes (transposons/integrons) in an extreme environment like
      Antarctica reinforces the hypothesis of the origin of some of the genes
      disseminated by mobile elements among "human-associated" microorganisms.

PMID- 21731971
TI  - Presence of enterotoxigenic Staphylococcus aureus in bulk tank milk from
      Argentine dairy farms.
AB  - Staphylococcus aureus is the most prevalent bovine mastitis pathogen in
      Argentina. The ability of this organism to produce enterotoxins is linked to
      staphylococcal food poisoning. Staphylococcal enterotoxins are low molecular
      weight proteins, highly resistant to heat and proteolytic enzyme activity. The
      aim of this study was to determine the ability to produce enterotoxins and types
      of enterotoxins A through E produced among 94 S. aureus isolated from bulk tank
      milk in Argentina by enzyme-linked immunosorbent assay. Eleven isolates (11.7 %)
      produced enterotoxins. Seven of them (7.4 %) produced enterotoxin C, two (2.1 %)
      enterotoxin D, one (1.1 %) enterotoxin B and one (1.1 %) enterotoxins C-D-E. None
      of the isolates produced enterotoxins A or E alone. Since presence of
      staphylococcal enterotoxins constitute a potential risk to public health, these
      findings underscore the need to control S. aureus bovine mastitis and to limit
      bacterial multiplication in bulk tank milk.

PMID- 21731972
TI  - Chemotactic responses to gas oil of Halomonas spp. strains isolated from saline
      environments in Argentina.
AB  - In this study, two halophilic bacterial strains isolated from saline habitats in
      Argentina grew in the presence of gas oil. They were identified as Halomonas spp.
      and Nesterenkonia sp. by 16S ribosomal RNA sequencing. Chemotaxis towards gas oil
      was observed in Halomonas spp. by using swimming assays.

PMID- 21731973
TI  - [Microbiological quality of the water used in a random sample from dairy farms in
      Cordoba, Argentina].
AB  - Bacteriological contamination of well water and wash water in a random sample
      obtained from 50 farms from Villa Maria (Cordoba) dairy area, Argentina, was
      evaluated during a visit in 2007. Forty six percent and 24 % of farms showed an
      aerobic mesophilic bacteria count higher than 500 CFU/ml in wash water and well
      water, respectively. Escherichia coli was isolated in 20 % of samples from both
      sources. Pseudomonas aeruginosa showed high frequency of isolation in well water
      (36 %) and wash water (42 %). Eighty and eighty-eight percent of dairy farms have
      contaminated well water and wash water, respectively. The findings show moderate
      concordance between contamination of well water and wash water for mesophilic
      aerobics and total coliforms. The results reveal that a high percentage of dairy
      farms in the basin under study have poor bacteriological water quality, not
      suitable for milking and washing facilities.

PMID- 21731974
TI  - [Comparative evaluation of the sensitivity of Acinetobacter to colistin, using
      the prediffusion and minimum inhibitory concentration methods: detection of
      heteroresistant isolates].
AB  - The objective of this study is to perform a comparative evaluation of the
      prediffusion and minimum inhibitory concentration (MIC) methods for the detection
      of sensitivity to colistin, and to detect Acinetobacter baumanii-calcoaceticus
      complex (ABC) heteroresistant isolates to colistin. We studied 75 isolates of ABC
      recovered from clinically significant samples obtained from various centers.
      Sensitivity to colistin was determined by prediffusion as well as by MIC. All the
      isolates were sensitive to colistin, with MIC = 2ug/ml. The results were analyzed
      by dispersion graph and linear regression analysis, revealing that the
      prediffusion method did not correlate with the MIC values for isolates sensitive
      to colistin (r2 = 0.2017). Detection of heteroresistance to colistin was
      determined by plaque efficiency of all the isolates with the same initial MICs of
      2, 1, and 0.5 ug/ml, which resulted in 14 of them with a greater than 8-fold
      increase in the MIC in some cases. When the sensitivity of these resistant
      colonies was determined by prediffusion, the resulting dispersion graph and
      linear regression analysis yielded an r2 = 0.604, which revealed a correlation
      between the methodologies used.

PMID- 21731975
TI  - [Evaluation of three methods for in vitro detection of antifungal susceptibility
      of Candida species].
AB  - Reference methods E.Def 7.1 and M27-A3 detect in vitro resistance; however, they
      are expensive and very laborious. Thus, their actual use in hospital laboratories
      is limited. There are commercial techniques available, having easier
      accessibility and development, which would yield results comparable to those of
      the reference methods. The objectives of this study were: a) to compare the
      results of minimal inhibitory concentration of 82 Candida spp. clinic isolates
      according to reference method E.Def 7.1 and ATB(r) Fungus 3; b) to compare the
      results of fluconazole susceptibility testing by disk diffusion in agar with Neo
      SensitabsTM tablets and Malbran disks with those of the reference methods.
      Minimal inhibitory concentration for amphotericin B, 5-flucytosine, fluconazole
      and itraconazole was performed according to the E.Def 7.1 and the ATB Fungus 3
      methods and diffusion was carried out with fluconazole disks and tablets. General
      concordance between the reference method and ATB Fungus 3 was 90.2 % and 96.3 and
      92.7% for diffusion with disks and tablets. The ATB Fungus 3 method was effective
      to determine susceptibility against amphotericin B and 5-flucytosine; however,
      discrepancies were observed with azole drugs. Disk diffusion methods are useful
      to determine susceptibility to fluconazole; however, 3 very major, 1 major and 2
      minor errors were observed with the tablets, whereas only 3 minor errors were
      observed with the disks.

PMID- 21731976
TI  - [Impact of the recent advances in the analysis of microbial communities on the
      control of the wastewater treatment process].
AB  - One of the main functions of environmental biotechnology is to address the study
      of microbial communities that provide essential services to society. Beyond the
      similarities with industrial and agricultural microbiology, the unique features
      exhibited by environmental biotechnology, such as process objectives, biomass
      characteristics and type and mode of feeding (substrates), allow a clear
      distinction from the other related disciplines. Recent advances in microbial
      ecology, ecophysiology, genomics and process engineering are herein reviewed to
      illustrate how the integration of the new knowledge can help overcome the
      shortcomings of classic microbiological analyses to understand, predict and
      optimize the performance of wastewater treatment.

PMID- 21731977
TI  - [Antimicrobial susceptibility testing in clinically relevant non-fermenting gram
      negative bacilli: recommendations from the Antimicrobial Agents Subcommittee of
      the Sociedad Argentina de Bacteriologia, Micologia y Parasitologia Clinicas,
      Asociacion Argentina de Microbiologia].
AB  - This document contains the recommendations for antimicrobial susceptibility
      testing of the clinically relevant non-fermenting gram-negative bacilli (NFGNB),
      adopted after conforming those from international committees to the experience of
      the Antimicrobial Agents Subcommittee members and invited experts. This document
      includes an update on NFGNB classification and description, as well as some
      specific descriptions regarding natural or frequent antimicrobial resistance and
      a brief account of associated resistance mechanisms. These recommendations not
      only suggest the antimicrobial drugs to be evaluated in each case, but also
      provide an optimization of the disk diffusion layout and a selection of results
      to be reported. Finally, this document also includes a summary of the different
      methodological approaches that may be used for detection and confirmation of
      emerging b-lactamases, such as class A and B carbapenemases.

PMID- 21731978
TI  - Anaesthetic management of a parturient with moyamoya disease.
AB  - Moyamoya disease is an uncommon progressive cerebral vasculopathy that is more
      frequently seen in the Asian population. It has been described sporadically in
      other parts of the world. Proper knowledge of the pathophysiology and institution
      of appropriate perioperative measures improves patient prognosis. We report a
      case of moyamoya disease for emergency Caesarean section at 37 weeks of
      gestation. Epidural anaesthesia was administered using 0.5 percent bupivacaine
      and 50 MUg fentanyl. A stable haemodynamic state was maintained using left
      lateral uterine displacement, intravenous crystalloids and ephedrine boluses. The
      patient suffered no neurological deficit and was discharged with a healthy baby
      four days after the surgery.

PMID- 21731979
TI  - Single-port access total laparoscopic hysterectomy for stage 1A1 cancer of the
      cervix.
AB  - We describe the first case of single-port access total laparoscopic hysterectomy
      with intracorporeal suturing of the vault performed in Singapore. A 40-year-old
      woman with microinvasive squamous cell carcinoma of the cervix successfully
      underwent single-port access total laparoscopic hysterectomy. Unique articulated
      and multifunction laparoscopic instruments were used to complete the surgery in
      118 minutes, with no complications. The patient had minimal pain postoperatively
      and recovered uneventfully within two weeks. This case illustrates the benefits
      of single-port access laparoscopic surgery in well-selected cases.

PMID- 21731980
TI  - Ectopic pregnancy in previous Caesarean section scar.
AB  - We report two cases of Caesarean scar pregnancies that were managed surgically.
      The first case was a 33-year-old woman who presented at 21 weeks of gestation
      with lower abdominal pain. An exploratory laparotomy was performed as she was
      hypotensive and had a drastic drop in haemoglobin level. Intraoperatively, a
      ruptured scar ectopic pregnancy with placenta percreta was found. A hysterectomy
      was performed in view of uncontrolled haemorrhage. The second case was a 30-year
      old woman who presented with irregular per vaginal spotting without abdominal
      pain. Ultrasonography revealed a gestational sac at a previous Caesarean scar,
      with interval increase in size and development of a yolk sac. On laparoscopy, the
      diagnosis of scar pregnancy was confirmed, and the gestational sac and
      surrounding myometrium were excised. Our case report shows that early diagnosis
      of scar pregnancy is important, as timely intervention can prevent life
      threatening complications and preserve fertility.

PMID- 21731981
TI  - Foetal sacrococcygeal teratoma: extremes in clinical presentation.
AB  - Sacrococcygeal teratoma (SCT) is a congenital tumour that can be diagnosed by
      ultrasonography (USG). We present our experience with the management of two cases
      of SCT in our institution between 2008 and 2009. In the first case, SCT was
      diagnosed at 17 weeks' gestation. The patient was followed up with fortnightly
      USG to monitor the tumour size, foetal growth and signs of foetal hydrops. The
      patient delivered a baby girl by Caesarean section at 37 weeks, with good Apgar
      scores. The neonate underwent an uneventful resection of SCT on Day 1 of life. In
      the second case, SCT was diagnosed at 20 weeks during screening. In view of
      foetal hydrops and anaemia, the patient underwent three in utero foetal blood
      transfusions. A baby boy was delivered by Caesarean section at 28 weeks. There
      was a large friable SCT with massive haemorrhage. Despite maximal resuscitative
      efforts, the neonate died 30 minutes after birth.

PMID- 21731982
TI  - Entangled bilateral adnexal torsion in a premenarchal girl: a laparoscopic
      approach.
AB  - Bilateral adnexal torsion is a rare event in children. A high index of suspicion,
      together with prompt surgical treatment, would help to save the ovaries and
      preserve its function. We report a case of entangled bilateral adnexal torsion
      managed successfully via laparoscopy. An 11-year-old premenarchal girl complained
      of chronic intermittent abdominal pain that worsened over 24 hours. Computed
      tomography of the abdomen and pelvis showed a bilobed cystic tumour (10 cm * 12
      cm * 12 cm and 3 cm * 4 cm) lying in the left abdomen and another cystic tumour
      (10 cm * 6 cm * 5 cm) in the pelvis. At laparoscopy, entangled bilateral adnexal
      torsion was seen. After disentanglement and detorsion of both adnexa, bilateral
      ovarian cystectomy was performed, and both ovaries were preserved. This case
      illustrates that laparoscopic treatment is possible for large entangled bilateral
      adnexal torsion in children.

PMID- 21731983
TI  - Recurrent Rapunzel syndrome.
AB  - Rapunzel syndrome is a rare condition that occurs when gastric trichobezoar
      extends beyond the pylorus and into the bowel. Recurrent Rapunzel syndrome is an
      extremely rare entity, with only two cases reported in the literature so far.
      Here, we present a case of recurrent Rapunzel syndrome in a 15-year-old girl. She
      underwent laparotomy twice in five years to extract trichobezoars measuring 58 cm
      and 62 cm. In both stances when Rapunzel syndrome was diagnosed, a tuft of hair
      extending from the stomach toward the jejunum was observed. The patient underwent
      psychiatric consultation and supervision after the first laparotomy; however, a
      lack of follow-up resulted in recurrence. We conclude that complete removal of
      trichobezoar and psychiatric consultation, coupled with long-term follow-up, are
      essential to prevent recurrence.

PMID- 21731984
TI  - Hypersexual features in Huntington's disease.
AB  - We report the case of a 30-year-old woman with a rare presentation of early
      adulthood Huntington's disease (HD) with hypersexuality. It is not known if
      sexual dysfunction in HD patients is due to a specific brain lesion or adverse
      psychosocial factors associated with HD. Although there are no evidence-based
      treatment guidelines for hypersexuality in HD, our patient exhibited significant
      improvement with olanzapine and haloperidol.

PMID- 21731985
TI  - Extrarenal teratoid Wilms' tumour.
AB  - We report an unusual case of extrarenal teratoid Wilms' tumour in a 15-month-old
      male child. The tumour was retroperitoneal in location and consisted of triphasic
      Wilms' tumour elements, along with the presence of heterologous components. The
      heterologous teratoid elements were composed of predominantly glandular
      epithelium with the presence of focal skeletal muscle, adipose and neuroglial
      tissues. Although extrarenal Wilms' tumours have been documented in the
      literature, only a few cases have been noted to date. We present the relevant
      clinical, radiological, histomorphological, histochemical and immunohistochemical
      features of this rare tumour, and discuss the various theories of its
      histogenesis.

PMID- 21731986
TI  - Peripheral type of primitive neuroectodermal tumour arising from the left orbital
      floor.
AB  - Primitive neuroectodermal tumours (PNETs) are rare tumours that originate from
      primitive neural crest cells. They are usually found in children below ten years
      of age. Peripheral PNETs (pPNETs) occur in soft tissues of the body, but have the
      same genetic changes as Ewing's sarcoma of the bone (now called soft tissue
      Ewing's sarcoma). They commonly present in the thoracopulmonary region, abdomen,
      pelvis and the extremities. The head and neck regions may also be involved. Our
      case demonstrates a PNET in the peripheral tissue arising from the left orbital
      floor and spreading locally to involve the left maxillofacial region, cheek and
      gum. The incidence of pPNETs is likely to be under-reported in the literature.
      Recent diagnostic advances, including cytogenetic and immunohistochemical
      analysis, have allowed these tumours to be distinguished from other small, poorly
      differentiated round cell tumours such as rhabdomyosarcoma, lymphoma and poorly
      differentiated synovial sarcoma.

PMID- 21731988
TI  - Jose Protacio Rizal (1861-1896): Physician and Philippine national hero.

PMID- 21731989
TI  - Electrocardiography Series. What is the cause of the regular wide QRS complex
      tachycardia?
AB  - Regular broad QRS complex tachycardias may be ventricular in origin or due to
      supraventricular tachycardia with aberrancy. Antidromic atrioventricular re
      entrant tachycardia occurring in Wolff-Parkinson-White syndrome is a third
      possibility. The electrocardiogram is a key tool for distinguishing these
      tachycardias, which have differing causes, prognoses and treatment strategies.
      Ventricular tachycardia may be monomorphic or polymorphic. The management of
      ventricular tachycardia depends on clinical symptoms and is influenced by the
      presence of structural heart disease.

PMID- 21731990
TI  - Half-dose ezetimibe add-on to statin therapy is effective in improving resistant
      hyperlipidaemia in Asian patients with ischaemic heart disease.
AB  - INTRODUCTION: Ezetimibe at full dose (10-mg) is used for lipid lowering. We
      hypothesised that ezetimibe at half dose is effective in achieving percentage
      improvement in lipid profile among Asian patients with severe hyperlipidaemia.
      METHODS: This was a prospective cohort study conducted between 2006 and 2008. 105
      patients with hyperlipidaemia not reaching target level with statin treatment
      alone were given add-on ezetimibe 5-mg daily treatment. Lipid profiles were
      compared at pre- and post-ezetimibe therapy. RESULTS: The mean age of the
      patients was 56.0 +/- 10.3 years. 79.0 percent were male and 62.9 percent had
      hypertension, 39 percent had diabetes mellitus with a mean HBA1c of 7.7 percent.
      58.1 percent had a history of myocardial infarction. The median simvastatin
      equivalent dose was 40 (range 5-80) mg. Duration of ezetimibe treatment was 102
      +/- 60 days. We observed improvements in total cholesterol (TC) (from 5.31 +/-
      1.02 to 4.33 +/- 1.11 mmol/l, 16.4 percent reduction, p-value less than 0.0005),
      low density lipoprotein (LDL) (from 3.43 +/- 0.87 to 2.52 +/- 0.95 mmol/l, 24.0
      percent reduction, p-value less than 0.0005) and TC to LDL ratio (from 4.92 +/
      1.42 to 4.03 +/-1.16, 16.2 percent reduction, p-value less than 0.0005). The
      percentage improvement of lipid profile was comparable to that of the published
      data based on 10-mg dosing. CONCLUSION: A 5-mg dose of daily ezetimibe add-on
      treatment is effective in improving lipid profiles in Asian patients with severe
      hyperlipidaemia not reaching target with statin monotherapy.

PMID- 21731991
TI  - Inter-fraction prostate motion during intensity-modulated radiotherapy for
      prostate cancer.
AB  - INTRODUCTION: This study aimed to analyse the inter-fraction prostate motion and
      setup error during intensity-modulated radiotherapy for prostate cancer at the
      National Cancer Centre Singapore. METHODS: Gold seeds were implanted as fiducial
      markers. Daily portal films were taken and displacements of the gold seeds from
      the isocentre in each axis were recorded. Random and systematic errors were used
      to derive a margin recipe for each axis based on the van Herk formula. RESULTS:
      1,077 fractions from 36 patients were analysed. 89.8 percent, 85.2 percent and
      83.6 percent of the setup errors were within +/- 2 mm for the right-left (RL),
      superior-inferior (SI) and anterior-posterior (AP) axes, respectively. The
      population systematic errors were 0.71 mm, 0.84 mm and 0.87 mm; the population
      random errors were 1.32 mm, 1.59 mm and 1.70 mm; the overall population mean
      setup errors were -0.14 (range -2.27 to 1.15) mm, 0.11 (range -2.32 to 1.69) mm
      and 0.08 (range -1.33 to 1.46) mm; and the van Herk margin recipes were 2.69 mm,
      3.22 mm and 3.37 mm for the RL, SI and AP axes, respectively. CONCLUSION: The
      setup errors and inter-fraction prostate movements were small. Gold seed
      implantation is a feasible and easy method of verifying the prostate position.

PMID- 21731992
TI  - Arterial vascularisation of the anterior perforated substance.
AB  - INTRODUCTION: The arteries of the anterior perforated substance (APS) are
      important due to their role in supplying blood to important internal structures
      such as the internal capsule, putamen and caudate nucleus. The purpose of this
      study was to investigate in detail the arteries of the APS. METHODS: The arteries
      of the APS were investigated in 60 cerebral hemispheres from 30 adult cadaveric
      brains. The internal carotid arteries were cannulated and perfused with coloured
      latex. The branches of the middle cerebral artery (MCA) penetrating the APS were
      investigated. These arteries, known as the lateral lenticulostriate arteries and
      originating from the M1 segment, early temporal and early frontal branches of the
      MCA, were recorded. RESULTS: The branches of the anterior choroidal artery, which
      reached the APS, were seen in all specimens. We found one to three branches that
      arose from the A2 segment of the anterior cerebral artery (ACA) to the APS in all
      hemispheres, and one to three branches that originated from the A1 segment of the
      ACA in 48 hemispheres. In addition, two accessory MCAs that originated from the
      A2 segment of the ACA were recorded as variations, and perforating branches to
      the APS were observed. CONCLUSION: Serious complications like motor deficits can
      occur as a result of injury to the arteries of the APS. Hence, neurosurgeons
      performing operations such as aneurysm or insular tumour surgeries must be aware
      of the importance of preserving these arteries.

PMID- 21731993
TI  - Aetiology of community-acquired urinary tract infection and antimicrobial
      susceptibility patterns of uropathogens isolated.
AB  - INTRODUCTION: Antibiotic resistance among uropathogens causing urinary tract
      infection (UTI) is increasing worldwide. In most cases of UTI, family physicians
      can provide empirical treatment without the benefit of a pre-therapy urine
      culture. Knowledge of the aetiology and antimicrobial susceptibility patterns of
      uropathogens is important in order to determine the best empiric treatment
      option. This study aimed to determine the aetiology and antimicrobial
      susceptibility of uropathogens in culture-positive, community-acquired UTIs over
      a one-year period. METHODS: This is a retrospective analysis of medical case
      records. All patients who were diagnosed and coded with UTI and had urine culture
      done were analysed. The prevalence of the UTI-causing organism and its antibiotic
      susceptibility was tabulated. Results were analysed with descriptive statistics.
      The chi-square and Fisher's exact tests were applied for categorical variables.
      RESULTS: The commonest organism isolated for all age groups and gender was
      Escherichia coli (74.5 percent) and Klebsiella spp. (8.7 percent). Among the oral
      antibiotics widely used in primary care in Singapore, the Enterobacteriaceae
      family was most susceptible to amoxicillin/clavulanate. There was no significant
      difference in the susceptibility of common oral antibiotics when tested against
      the Enterobacteriaceae for both male and female patients and between patients
      older than 65 years and those 65 years and below. CONCLUSION: Empirical treatment
      of community-acquired UTI with cotrimoxazole, ciprofloxacin, cephalothin and
      ampicillin is inadequate. Amoxicillin/clavulanate should be the drug of choice
      for empirical treatment instead.

PMID- 21731994
TI  - Attitudes of rehabilitation medicine doctors toward medical ethics in Malaysia.
AB  - INTRODUCTION: Medical ethics issues encountered in rehabilitation medicine differ
      from those in an acute care setting due to the complex relationships among the
      parties involved in rehabilitative care. The study examined the attitudes of
      Malaysian rehabilitation doctors toward medical ethics issues commonly
      encountered during patient care. METHODS: We surveyed 74 rehabilitation
      physicians and residents in Malaysia using a self-administered descriptive
      questionnaire. The questions covered medical ethics issues on allocation of
      resources, patient confidentiality, discharge planning, goal-setting,
      reimbursement documentation, decision-making capacity and withdrawal of life
      support. RESULTS: The overall response rate was 69 percent. More than 80 percent
      of respondents would disclose confidential information to their team members if
      it would affect the rehabilitation process. More than two-thirds of respondents
      would not allocate scarce rehabilitation resources if the functional outcome is
      marginally positive. Issues involving patients' autonomy in decision-making, both
      in life-threatening and non-life-threatening situations, showed mix responses.
      The least common response was on the issue of discharge planning, where 51
      percent of respondents would send a patient back to a nursing home with
      suboptimal care if there were no other alternatives. CONCLUSION: The attitude of
      Malaysian rehabilitation doctors toward ethical issues is reflective of the level
      of maturity of rehabilitation medicine in Malaysia. Issues on allocation of
      resources, discharge planning and decision-making capacity are significantly
      influenced by limited rehabilitation facilities in parts of the country. The lack
      of influence from external factors, such as a developed health insurance system,
      contributes to the difference in attitude between rehabilitation doctors in
      Malaysia and those in developed countries.

PMID- 21731995
TI  - Are the demographic and clinical features of pathological gamblers seeking
      treatment in Singapore changing?
AB  - INTRODUCTION: The expansion in gambling activities over the past decade has made
      gambling more accessible than ever. This could bring changes in the
      sociodemographic and clinical profiles of those seeking treatment for
      pathological gambling. METHODS: This study examined the differences between two
      cohorts of 150 patients each, treated at the National Addictions Management
      Service between 2001 and 2006 (cohort-1) and between 2006 and 2008 (cohort-2),
      respectively. RESULTS: Compared to cohort-1, cohort-2 was significantly younger
      (p-value less than 0.01), comprised fewer Chinese and were more highly educated
      (p-value less than 0.05), with no significant difference in gender or marital
      status. Regarding the type of gambling activities, cohort-2 was more likely to
      engage in soccer betting (p-value less than 0.01). Although the proportion
      presenting with any comorbidity remained unchanged, alcohol use disorders had
      increased more than three-fold and suicide risk was slightly elevated, although
      not significantly. DISCUSSION: Clinicians should undertake routine screening and
      assessment of alcohol misuse and suicide risk, offering brief interventions,
      where necessary, for this vulnerable population.

PMID- 21731996
TI  - Effects of intrathecal midazolam in spinal anaesthesia: a prospective randomised
      case control study.
AB  - INTRODUCTION: Subarachnoid block with local anaesthetics and adjuvants has been
      extensively used for surgery. Intrathecal midazolam produces antinociception and
      potentiates the effect of local anaesthetics. We compared intrathecal bupivacaine
      with and without midazolam to assess its effect on the duration of sensory block,
      motor block and pain relief. METHODS: A total of 100 patients scheduled for
      elective lower abdominal, lower limb and gynaecological procedures were selected
      to participate in this prospective, randomised, double-blind study. Patients were
      randomly allocated into two groups for intrathecal drug administration. Group B
      received 3 mL 0.5 percent bupivacaine with 0.4 mL saline, and group BM received 3
      mL 0.5 percent bupivacaine and 0.4 mL (2 mg) midazolam mixture. The onset,
      duration of sensory/motor block, time to first rescue analgesia and side effects
      were noted. RESULTS: Demographic profile and duration of surgery were comparable
      between the two groups. The onset of sensory (4.8 versus 4.6 min) and motor block
      (5.9 versus 6 min) was also comparable between the groups. The duration of
      sensory blockade was prolonged in the midazolam group (90.8 versus 115.8 min, p
      value is 0.001), while the duration of motor blockade was comparable (151.8
      versus 151.3 min, p-value is 0.51). The duration of effective analgesia was
      significantly longer in the midazolam group compared to the control group (121.3
      versus 221.1 min, p-value is 0.001). Sedation score was comparable in the two
      groups. CONCLUSION: The addition of preservative-free midazolam to bupivacaine
      intrathecally resulted in prolonged postoperative analgesia without increasing
      motor block.

PMID- 21731997
TI  - Treatment of Brodie's abscess: excellent results from curettage, bone grafting
      and antibiotics.
AB  - INTRODUCTION: Brodie's abscess is not a common variant of subacute osteomyelitis;
      however, when it does occur, the presentation is atypical and usually late. This
      study aimed to describe the mode of presentation of Brodie's abscess and evaluate
      the results of surgical treatment in a resource-poor setting. METHOD: Over a five
      year period, we retrospectively reviewed 20 patients who presented to two
      tertiary health institutions in south western Nigeria with clinical and
      radiological features of Brodie's abscess. RESULTS: Brodie's abscess accounted
      for just 2 percent of all patients with osteomyelitis. Most patients were adults
      (mean age 21.5 +/- 7.8 years) and males (75 percent). In the series, the tibia
      was involved in 50 percent of the cases, the femur in 30 percent, and the radius
      and fibula each in 10 percent. The diaphyseal part of the long bones was affected
      in 65 percent of the patients and the metaphysis, in the remaining patients. The
      average size of the cavities was 3.0 +/- 0.8 cm. 65 percent of the isolates
      yielded Staphylococcus aureus. All patients were treated by curettage of the
      abscess cavities, cancellous bone grafting and antibiotics. All patients had
      satisfactory outcomes, with complete incorporation of the grafts and new bone
      formation in the cavities. No patient reported any recurrence. CONCLUSION:
      Patients with Brodie's abscess respond well to surgical curettage of the abscess,
      cancellous bone grafting and antibiotic therapy.

PMID- 21731998
TI  - Recurrent vertebral hydatid disease: spectrum of MR imaging features.
AB  - INTRODUCTION: This study aimed to describe a spectrum of magnetic resonance (MR)
      imaging findings in a case series of four patients with recurrent vertebral
      hydatid disease (HD). METHODS: Four patients with recurrent spinal HD, who were
      studied with MR imaging at 1.5T or 0.5T MR units, were encountered during a ten
      year period. All patients had a history of repeated spinal surgery for hydatid
      resection. RESULTS: HD involving the lumbar spine was found in two patients, the
      thoracolumbar spine in one patient and the lumbosacral in one patient. Skip
      lesions were seen in one patient. All patients had extensive involvement of the
      extradural space, soft tissues of the back and posterior vertebral elements. HD
      involving the vertebral body, intervertebral disk and iliopsoas muscles were
      noted in three, two and three patients, respectively. Bone and extradural
      hydatids were typically small, and appeared hypointense on T1-weighted images,
      with a mildly enhancing rim on post-contrast T1-weighted images. Sacral hydatid
      was an expansile multicystic process. Muscle hydatids were large, surrounded by a
      gadolinium-enhancing rim and assumed a variety of patterns - either multilocular
      or a nonspecific inhomogenous cystic or dumbbell configuration. CONCLUSION: MR
      imaging is a valuable diagnostic tool for follow-up of patients with vertebral
      HD. Recurrent HD is characterised by extensive involvement of soft tissues of the
      back and extradural space. Extension into the intervertebral disk and iliopsoas
      muscles and skip lesions in the extradural space are not uncommon.

PMID- 21731999
TI  - Association of serum C-reactive protein and leptin levels with wasting in
      childhood tuberculosis.
AB  - INTRODUCTION: Wasting is a systemic manifestation of tuberculosis (TB) and is
      often thought to affect the severity and outcome of the disease. Leptin and
      several cytokines/proteins are thought to play a role in the relationship between
      TB, nutritional status and host immune response. The aim of this study was to
      determine the association of C-reactive protein (CRP), an inflammatory response
      protein and serum leptin levels with wasting in childhood TB. METHODS: A cross
      sectional observational analytic study was conducted at two hospitals in West
      Java from January to March 2010. The subjects were 13 children aged 2-120 months
      who were infected with TB and 26 healthy children of the same age and gender as
      the comparison group. History-taking and anthropometric, physical, serum CRP and
      leptin examinations were conducted for each subject. The association of CRP and
      serum leptin levels with wasting in childhood TB was studied. RESULTS: Serum
      leptin levels were lower (95 percent confidence interval [CI] 314.0-1,228.9
      pg/mL, p-value less than 0.001) and serum CRP levels were higher (95 percent CI
      16.5-81.1 mg/L) in the subjects than in the comparison group. There were positive
      correlations between leptin and body mass index (p-value less than 0.001) and
      between CRP and wasting (p-value less than 0.001), but a negative correlation
      between leptin and wasting (p-value less than 0.001). CONCLUSION: Elevated serum
      CRP levels and a decrease in serum leptin levels are associated with an increase
      in wasting in childhood TB.

PMID- 21732000
TI  - Ministry of Health clinical practice guidelines: management of gambling
      disorders.
AB  - The Ministry of Health (MOH) has published clinical practice guidelines on
      Management of Gambling Disorders to provide doctors and patients in Singapore
      with evidence-based guidance on the management of gambling disorders. This
      article reproduces the introduction and executive summary (with recommendations
      from the guidelines) from the MOH clinical practice guidelines on Management of
      Gambling Disorders for the information of readers of the Singapore Medical
      Journal. Chapters and page numbers mentioned in the reproduced extract refer to
      the full text of the guidelines, which are available from the Ministry of Health
      website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=26136). The
      recommendations should be used with reference to the full text of the guidelines.
      Following this article are multiple choice questions based on the full text of
      the guidelines.

PMID- 21732001
TI  - Chronic cough: a myriad of aetiologies.

PMID- 21732003
TI  - Feedback interventions for impaired self-awareness following brain injury: a
      systematic review.
AB  - OBJECTIVE: To determine the effectiveness of self-awareness interventions that
      involve a component of feedback for adults with brain injury. DESIGN: Systematic
      review. DATA SOURCES: Randomized and non-randomized studies identified by
      searching CINAHL, Cochrane Systematic Review Database, Embase, Medline, OTSeeker,
      PsycBITE, PsycINFO, Web of Science, clinical trial registries, and reference
      lists of eligible articles. RESULTS: Twelve studies of varied methodological
      quality met the inclusion criteria, of which 3 were randomized controlled trials
      involving a total of 62 people with brain injury of mixed aetiology. The type of
      feedback intervention and outcomes assessed were heterogeneous. The pooled
      estimate of improvement in self-awareness after completing a feedback
      intervention was of moderate effect size (Hedges' adjusted g = 0.64; 95%
      confidence interval: 0.11-1.16). CONCLUSION: Feedback interventions produced
      modest improvements in self-awareness. Further research is required to determine
      the effects of integrating feedback interventions into rehabilitation programmes
      and the impact of this on functional outcome.

PMID- 21732004
TI  - Determinants of major direct medical cost categories among patients with
      osteoporosis, osteoarthritis, back pain or fibromyalgia undergoing outpatient
      rehabilitation.
AB  - OBJECTIVE: To identify determinants of direct medical costs among patients with
      osteoporosis, osteoarthritis, back pain or fibromyalgia. DESIGN: Cross-sectional
      study. PARTICIPANTS: Convenience sample of 410 patients undergoing outpatient
      rehabilitation. METHODS: Resource use was assessed with a self-report
      retrospective questionnaire, and direct medical costs were calculated considering
      outpatient physician services, non-physician health services, medication and
      inpatient treatment. Non-parametric bootstrap techniques with 1,000 replications
      were used to estimate means of costs and their 95% confidence intervals (CI). To
      identify determinants of costs, a generalized linear model with log link function
      and gamma distribution, as well as a multivariate logistic regression analysis,
      were performed. RESULTS: Medical indication (p < 0.001), age (p = 0.034) and the
      scales of the Short Form-36 (SF-36) role physical (p < 0.001), physical
      functioning (p = 0.036), social functioning (p = 0.047) and vitality (p = 0.005)
      were significant predictors of direct medical costs, whereas the medical
      indication fibromyalgia (odds ratio (OR) = 5.74, 95% CI 2.051-16.066, p = 0.001),
      the Short-Form 36 (SF-36) scale role physical (OR = 0.988, 95% CI 0.980-0.996, p
      = 0.002) and comorbidity (OR = 1.161, 95% CI 1.043-1.292, p = 0.006) were
      statistically significant determinants of high direct medical costs beyond the
      median. CONCLUSION: Our work confirms known predictors of direct medical costs
      and broadens the understanding of determinants of direct medical costs beyond the
      median.

PMID- 21732005
TI  - Changes in skills required for using a manual wheelchair after reconstructive
      hand surgery in tetraplegia.
AB  - OBJECTIVE: The aim of this study was to document prospectively the changes in
      function that can affect the skills required to use a manual wheelchair after
      reconstructive hand and arm surgery in individuals with tetraplegia. DESIGN: Case
      series. The tests were conducted preoperatively and 12 months postoperatively.
      PATIENTS: Sixteen individuals who underwent a total of 23 grip/elbow extension
      reconstructions and who used a manual wheelchair as their main form of transport
      were included. METHODS: Functional tests of wheelchair control were performed.
      The tests addressed 8 aspects of manoeuvring a wheelchair. RESULTS: Sixty-eight
      percent of the individuals improved their manoeuvring skills after hand surgery.
      Improvements were also observed in the ability successfully to perform tests that
      were impossible to perform before surgery. The type of reconstruction and level
      of injury affected the outcome. CONCLUSION: The improvement in wheelchair
      propulsion ability after reconstructive hand and arm surgery in individuals with
      tetraplegic spinal cord injury implies increased mobility, which can help
      individuals to live a more active life.

PMID- 21732006
TI  - Left-ventricular function and autonomic cardiac adaptations after short-term
      inpatient cardiac rehabilitation: a prospective clinical trial.
AB  - OBJECTIVE: Cardiac rehabilitation is associated with cardiac autonomic and
      physiological benefits. However, it is unclear whether baseline left ventricular
      function (LVF) impacts on training-induced cardiac autonomic adaptations. The aim
      of this study was to assess the cardiac autonomic adaptations in patients with
      varying left ventricular function profiles undergoing coronary artery bypass
      grafting and cardiac rehabilitation. DESIGN: Assessor-blinded prospective trial.
      PATIENTS: Forty-four patients undergoing coronary artery bypass grafting, divided
      into normal LVFN (>= 55%, n = 23) or reduced LVFR (35-54%, n = 21) were
      evaluated. METHOD: Cardiac autonomic function was evaluated by heart rate
      variability indexes obtained both pre- and post-cardiac rehabilitation. All
      patients participated in a short-term (approximately 5 days) supervised inpatient
      physiotherapy program. RESULTS: There were differences in heart rate variability
      indexes, correlation dimension and SD2 according to time and group (e.g.
      interaction time (effect of cardiac rehabilitation) vs group (LVFN vs LVFR), p =
      0.04). Simple main effects analysis showed that the LVFR group benefited to a
      greater degree from cardiac rehabilitation compared with the LVFN group. Heart
      rate variability indexes increased significantly in the former group compared
      with the latter. CONCLUSION: Among post-coronary artery bypass grafting patients
      engaged in short-term inpatient rehabilitation, those with reduced left
      ventricular function are most likely to have better cardiac autonomic adaptations
      to exercise-based rehabilitation.

PMID- 21732007
TI  - Using content analysis to link texts on assessment and intervention to the
      International Classification of Functioning, Disability and Health - version for
      Children and Youth (ICF-CY).
AB  - OBJECTIVE: To explore how content analysis can be used together with linking
      rules to link texts on assessment and intervention to the International
      Classification of Functioning, Disability and Health - version for children and
      youth (ICF-CY). METHODS: Individual habilitation plans containing texts on
      assessment and intervention for children with disabilities and their families
      were linked to the ICF-CY using content ana-lysis. Texts were first divided into
      meaning units in order to extract meaningful concepts. Meaningful concepts that
      were difficult to link to ICF-CY codes were grouped, and coding schemes with
      critical attributes were developed. Meaningful concepts that could not be linked
      to the ICF-CY were assigned to the categories "not-definable" and "not-covered",
      using coding schemes with mutually exclusive categories. RESULTS: The size of the
      meaning units selected resulted in different numbers and contents of meaningful
      concepts. Coding schemes with critical attributes of ICF-CY codes facilitated the
      linking of meaningful concepts to the most appropriate ICF-CY codes. Coding
      schemes with mutually exclusive categories facilitated the classification of
      meaningful concepts that could or could not be linked to the ICF-CY. CONCLUSION:
      Content analysis techniques can be applied together with linking rules in order
      to link texts on assessment and intervention to the ICF-CY.

PMID- 21732009
TI  - Membrane proteins: the key players of a cancer cell.
AB  - Membrane proteins are involved in the prognosis of the most common forms of
      cancer. Membrane proteins are the hallmark of a cancer cell. The overexpressed
      membrane receptors are becoming increasingly important in cancer cell therapy.
      Current renewing therapy approaches based on receptor overexpression include;
      antibody therapy, nanocarrier drug delivery, and fluorescent tumor imaging in
      surgery. Gene profiling reveals cancer specific signatures and may identify
      membrane proteins that are related to cancer progression and lead to the
      development of improved therapy strategies in the future.

PMID- 21732010
TI  - Phospholipid dependence of the reversible, energy-linked, mitochondrial
      transhydrogenase in Manduca sexta.
AB  - Midgut mitochondria from fifth larval instar Manduca sexta exhibit a membrane
      associated transhydrogenase that catalyzes hydride ion transfer between NADP(H)
      and NAD(H). The NADPH-forming transhydrogenations occur as nonenergy- and energy
      linked activities. The energy-linked activities couple with electron transport
      dependent utilization of NADH/succinate, or with Mg(2+)-dependent ATPase. These
      energy-linked transhydrogenations have been shown to be physiologically and
      developmentally significant with respect to insect larval/pupal maturation. In
      the present study, isolated mitochondrial membranes were lyophilized and
      subjected to organic solvent or phospholipase treatments. Acetone extraction and
      addition of Phospholipase A(2) proved to be effective inhibitors of the insect
      transhydrogenase. Liberation of phospholipids was reflected by measured
      phosphorous release. Addition of phospholipids to organic solvent- and
      phospholipase-treated membranes was without effect. Employing a partially lipid
      depleted preparation, phosphatidylcholine, phosphatidylethanolamine and
      phosphatidylserine were reintroduced and transhydrogenase activity assessed. Of
      the phospholipids tested, only phosphatidylcholine significantly stimulated
      transhydrogenase activity. The results of this study suggest a phospholipid
      dependence of the M. sexta mitochondrial transhydrogenase.

PMID- 21732011
TI  - Palytoxin induces functional changes of anion transport in red blood cells:
      metabolic impact.
AB  - Palytoxin (PTX) is classified as one of the most powerful marine biotoxins (of
      high molecular weight and no protein origin) because it is able to interact
      strongly with important cellular structures influencing their function in
      different biological processes. This study of the effects of PTX on red blood
      cells (RBC) extends the knowledge about its toxicity, which concerns not only the
      well-known action on Na(+)/K(+)-ATPase but also band 3 protein (B3 or AE1), the
      role of which is essential for anion transport and for the structure, function,
      and metabolic integrity of the erythrocyte. The effects of PTX on RBC can be
      summarized as follows: it alters the anionic flux and seriously compromises not
      only CO(2) transport but also the metabolic modulation centered on the oxy-deoxy
      cycle of hemoglobin; it stabilizes the plasma membrane by preventing lipid
      peroxidation; and its effect does not lead to activation of caspases 3 and 8.
      From what is reported in steps 2 and 3, and on the basis of the results obtained
      on hemolysis, methemoglobin levels, and phosphatase activity, an increase of the
      reducing power of the erythrocytes (RBC) in the presence of PTX clearly emerges.
      The results have enabled us to outline some metabolic adaptations induced in the
      RBC by PTX.

PMID- 21732012
TI  - Severe combined immunodeficiency in Greek children over a 20-year period: rarity
      of gammac-chain deficiency (X-linked) type.
AB  - Severe combined immunodeficiencies (SCID) are a heterogeneous group of genetic
      disorders characterized by a blockade or impairment of both cellular and humoral
      immunity. Several epidemiological studies in different geographic areas have
      shown that the most common type of SCID affecting almost half of these patients
      is the X-linked common gamma-chain (gamma(c)) deficiency. The objective of the
      study was to document the incidence and types of SCID in our area. We conducted a
      retrospective analysis of patients who were diagnosed with SCID in the major
      immunology center in Greece for a 20-year period. During the study period, 30
      children from 27 unrelated families with final diagnosis of SCID were identified.
      The incidence of SCID in Greece is estimated at 1.7 cases per 100,000 live
      births. Out of 30 children, 19 were boys (63.3%) and 26 (86.7%) had Greek
      maternal origin. Lymphocyte immunophenotypes that were identified were T(-)B(
      )NK(+) in 12 (40%) children, T(-)B(+)NK(-) in six (20%), T(-)B(+)NK(+) in three
      (10%), T(-)B(-)NK(-) in two (6.7%) and T(+)B(+/-)NK(+) in seven (23.4%) (among
      them, four [13.4%] females with Omenn's syndrome). Molecular diagnosis was
      available for 12 children: gamma(c) (2) with non Greek maternal origin, Jak3 (2),
      Rag1 (2), Artemis (3), ADA deficiency (2), PNP deficiency (1). Out of the 26
      children of Greek maternal origin diagnosed with SCID representing 23 distinct
      families, only two (8.7%) had lymphocyte immunophenotype compatible with gamma(c)
      chain gene mutation (no molecular testing or enough DNA was available for them at
      the time of diagnosis). Findings of the present study suggest that, for unknown
      reasons, mutations of the gamma(c) chain of several cytokine receptors have a
      rare occurrence in our area.

PMID- 21732013
TI  - Individual antibody and T cell responses to vaccination and infection with the
      2009 pandemic swine-origin H1N1 influenza virus.
AB  - INTRODUCTION: The 2009 swine-origin H1N1 influenza virus (swH1N1) provided an
      opportunity to study immune responses to a new influenza strain in the context of
      seasonal influenza vaccination. Our goals were: to assess whether analyzing
      multiple parameters of immune responsiveness to influenza has an advantage over
      evaluating hemagglutination inhibition (HAI) titer alone, to determine whether
      vaccination with the seasonal vaccine induced cross-reactive immunity to swH1N1
      in some individuals, and to determine whether the immune response against swH1N1
      is higher after infection than vaccination. METHODS: Antibody and T cell
      responses were studied in ten subjects who were first immunized with the 2009
      2010 seasonal influenza subunit vaccine, then 6 weeks later with the swH1N1
      monovalent subunit vaccine. The amount of antibody against native virus
      glycoproteins, overall avidity of these antibodies, and HAI titer were measured.
      T cells were evaluated for proliferation and IFNgamma secretion in response to
      the vaccine in vitro. Individuals with influenza-like illness were also
      evaluated, adding a microplate neuraminidase inhibition (NAI) test. RESULTS: The
      immune response to influenza was highly variable and immune parameters did not
      increase in parallel. The seasonal vaccine induced antibodies recognizing the
      pandemic virus in 50% of subjects. Antibody affinity and NAI activity to swH1N1
      were higher after natural infection than vaccination. CONCLUSIONS: The evaluation
      of several immune parameters gives a more complete measure of immune
      responsiveness to influenza infection or vaccination than the HAI test alone.

PMID- 21732014
TI  - KRN/I-Ag7 mouse arthritis is independent of complement C3.
AB  - BACKGROUND: KRN/I-A(g7) (KxB/N) is a mouse model of inflammatory arthritis, which
      resembles human rheumatoid arthritis. Arthritis in these animals is caused by
      autoreactivity to a ubiquitously expressed autoantigen, glucose-6 phosphate
      isomerase. Tolerance is broken at both the T cell and B cell level. The sera from
      KRN/I-A(g7) mice can induce mouse arthritis in healthy mice. Complement
      components of the alternative complement pathway, including C3, have been shown
      to be required in induction of mouse arthritis by serum transfer. METHODS: We
      have bred KRN/I-A(g7) mice onto a C3-deficient background and followed cohorts
      for the spontaneous appearance of arthritis. We have also transferred KxB/N serum
      to B6.I-A ( g7 ) recipients. RESULTS: C3-deficient KRN/I-A(g7) mice spontaneously
      developed severe, destructive arthritis, comparable to that seen in C3-intact
      KRN/I-A(g7) mice. However, serum transfer experiments confirmed the strong
      requirement for C3 in the passive model. CONCLUSION: The pathogenesis of
      spontaneous KRN/I-A(g7) arthritis can largely proceed by complement-independent
      pathways and must have pathology effector mechanisms in addition to those seen in
      the passive serum transfer model.

PMID- 21732015
TI  - TRAIL is associated with impaired regulation of CD4+CD25- T cells by regulatory T
      cells in patients with rheumatoid arthritis.
AB  - Thirty-five rheumatoid arthritis (RA) patients and 27 healthy volunteers were
      enrolled in the study. Regulatory T (Treg) cell numbers were significantly
      reduced in RA patients. RA Treg cells exhibited an impaired capacity to inhibit
      proliferation and cytokine secretion of autologous T effector (Teff) cells.
      However, the crossover experiments further indicated that this impaired
      suppression was due to resistance of Teff cells but not to an intrinsic defect of
      Treg cells in RA patients. RA Teff cells showed a higher expression of membrane
      tumor necrosis factor-related apoptosis-inducing ligand and secreted more soluble
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL could
      induce apoptosis in Treg cells. Neutralization of TRAIL restored the regulation
      of Teff by Treg in RA patients. In summary, our data suggest that reduced
      peripheral Treg cell numbers and an increased resistance of Teff cells to
      suppression by Treg cells were present in RA patients, and TRAIL may be an
      underlying mechanism for the impaired regulation of Teff cells by Treg cells.

PMID- 21732016
TI  - Serum fructosamine and retinopathy of prematurity.
AB  - OBJECTIVE: To determine whether serum fructosamine which is a good marker for
      detecting hyperglycemia during the previous 2 to 3 wk in infants could predict
      the development of retinopathy of prematurity in very low birth weight infants.
      METHODS: One hundred sixty seven premature infants who had a birth weight of <
      1500 g and a gestational age of less than 32 wk were investigated in the present
      study. Blood glucose was measured at the bedside and infants were recorded as
      hyperglycemic if their mean blood glucose levels were higher than 150 mg/dL.
      Serum corrected fructosamine level was obtained from the cord blood at birth and
      after the first month of life. The infants' eyes were examined by
      ophthalmologists to detect retinopathy of prematurity at the gestational age of
      32 wk or at four wk after birth, whichever came first. RESULTS: Corrected
      fructosamine was 319.6 +/- 59.6 and 272.8 +/- 50.6 mmol/l for group 1 on 1(st)
      and 30(th) day respectively; 320 +/- 61.7 and 268.2 +/- 47.3 mmol/l for groups 2
      + 3 on 1(st) and 30(th) day respectively which did not differ between groups (p =
      0.766 and p = 0.665), whereas duration of hyperglycemia was 1.69 +/- 1.1 day in
      group 1 compared with 3.05 +/- 2.4 day in groups 2 + 3 which was significantly
      different (p = 0.019). The multivariate regression analysis indicated that the
      duration of hyperglycemia in days was significantly correlated with the
      development of retinopathy of prematurity (OR 3.26; 95% CI 1.09-9.80; p = 0.035).
      CONCLUSIONS: Although the duration of hyperglycemia may contribute to the
      development of retinopathy of prematurity, serum corrected fructosamine does not
      have a good predictive value in developing retinopathy of prematurity in very-low
      birth-weight (VLBW) infants.

PMID- 21732017
TI  - Novel mutation in a child with Goltz syndrome.
AB  - Goltz syndrome or focal dermal hypoplasia is a rare clinical syndrome presenting
      with cutaneous, skeletal, dental, ocular, central nervous system and soft-tissue
      defects. The authors report a female child clinically diagnosed as Goltz
      syndrome, confirmed to have a novel splice site mutation IVS2 + 1G > A of PORCN
      gene. Review of the 80 or so pathogenic mutations reported in the literature
      shows this to be a new mutation.

PMID- 21732018
TI  - Congenital hepatic arteriovenous malformation presenting with severe persistent
      pulmonary hypertension.
AB  - Congenital hepatic arteriovenous malformation is a rarely seen vascular
      malformation with persistent pulmonary hypertension in neonates. The authors
      report a full-term female newborn presenting with intractable heart failure and
      respiratory distress soon after birth. Investigation by echocardiography showed
      severe persistent pulmonary hypertension of the newborn and patent ductus
      arteriosus. The hepatic angiogram revealed congenital hepatic arteriovenous
      malformation; therefore, secondary pulmonary artery hypertension complicated with
      'steal' phenomenon was conclusively diagnosed.

PMID- 21732019
TI  - Hypercalcemia in extremely low birth weight neonates.
AB  - Hypercalcemia is rare in neonates but may be associated with hypophosphatemia in
      Extremely low birth weight (ELBW) neonates who are on parenteral nutrition
      without adequate phosphate supplementation.

PMID- 21732020
TI  - Molecular detection of murine herpesvirus 68 in ticks feeding on free-living
      reptiles.
AB  - The MHV-68 (designed as Murid herpesvirus 4 (MuHV 4) strain 68) isolated from two
      rodents, Myodes glareolus and Apodemus flavicollis, is considered as a natural
      pathogen of free-living murid rodents. Recently, the detection of MHV antibodies
      in the blood of animals living in the same biotope as MHV-infected mice has
      suggested that ticks may have a role in the transmission of this pathogen. Ixodes
      ricinus is one the most abundant tick species in Europe known to transmit
      multiple pathogens causing human and animal diseases. In this study, nymphs and
      larvae feeding on 116 individuals of a temperate lizard species-the green lizard
      Lacerta viridis captured in the Slovak Karst National Park, were examined for MHV
      68. The specific sequence of virion glycoprotein 150 was amplified in DNA
      individually isolated from I. ricinus ticks using single-copy sensitive nested
      polymerase chain reaction. MHV-68 was detected in ten of 649 nymphs and in five
      of 150 larvae, respectively. We found that 9.6% of green lizards fed at least one
      MHV-68-infected immature tick. Occurrence of MHV-68 within all ticks tested was
      1.8%. This study is first to show that immature I. ricinus ticks feeding on free
      living lizards in a Central European region could be infected with
      gammaherpesvirus (MHV-68), naturally infecting free-living murid rodents. Our
      results provide evidence supporting the hypothesis that ticks may play a
      mediating role in circulation of MHV-68 in nature.

PMID- 21732022
TI  - Orthopaedic case of the month: A 25-year-old man with a paramedian painful lump
      over the anterior chest wall.

PMID- 21732023
TI  - Similar local control between phenol- and ethanol-treated giant cell tumors of
      bone.
AB  - BACKGROUND: Giant cell tumors (GCTs) of bone often are treated with curettage,
      adjuvant therapy, and cementation. Phenol is a commonly used adjuvant associated
      with local control rates ranging from 9% to 25%. However, it is corrosive to the
      eyes, skin, and respiratory tract. Ethanol is readily available and does not
      cause chemical burns on contact, but it is unclear whether ethanol can achieve
      similar local control rates as phenol for treating GCTs. QUESTIONS/PURPOSES: We
      evaluated (1) the recurrence rate and recurrence-free Kaplan-Meier survival
      function, (2) Musculoskeletal Tumor Society (MSTS) functional score (1993
      version), and (3) complications of two groups of patients with GCTs treated with
      extensive curettage, local adjuvant therapy with phenol or ethanol, and cement
      reconstruction, to determine if ethanol was a reasonable alternative to phenol.
      PATIENTS AND METHODS: We retrospectively reviewed all 26 patients with GCTs in
      the long bones of extremities treated with curettage, high-speed burring,
      phenolization, and cementation between May 1995 and November 2001, and 35
      patients treated with the same protocol, except phenol was replaced with 95%
      ethanol, between November 2001 and November 2007. The recurrence rates, Kaplan
      Meier recurrence-free survival curves, and MSTS functional scores of these two
      treatment groups were compared with Fisher's exact test, Tarone-Ware test, and
      Mann-Whitney U test, respectively. The minimum followup was 36 months (mean, 58
      months; range, 36-156 months). RESULTS: Local recurrence rates were similar in
      the two groups: 11% in the ethanol group and 12% in the phenol group. The
      survival curves (using local recurrence as an endpoint) of the two groups were
      similar. The mean MSTS functional score was 27.3 (91%) for the ethanol group and
      26.9 (90%) for the phenol group. CONCLUSIONS: Ethanol is a reasonable alternative
      to phenol when adjuvant therapy is considered in the treatment of GCTs of long
      bones. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 21732024
TI  - No long-term difference between fixed and mobile medial unicompartmental
      arthroplasty.
AB  - BACKGROUND: Early studies in the literature reported relatively high early minor
      reintervention rate for the mobile-bearing unilateral knee arthroplasty (UKA)
      compared with short- and midterm survivorship after fixed- or mobile-bearing UKA.
      However, whether the long-term function and survivorship are similar is unclear.
      QUESTIONS/PURPOSES: We therefore asked whether (1) mobile- or fixed-bearing UKAs
      have comparable function (as measured by the Knee Society scores); (2) mobile-
      and fixed-bearing UKA have comparable Knee Society radiographic scores; and (3)
      the long-term survivorship is comparable. METHODS: We retrospectively reviewed 75
      patients (79 knees) with a fixed-bearing UKA and 72 patients (77 knees) with a
      mobile-bearing UKA operated on between 1989 and 1992. Mean age of the patients
      was 63 years; gender and body mass index (26 kg/m(2)) were comparable in the two
      groups. We obtained Knee Society function and radiographic scores and determined
      survival. The minimum followup was 15 years (mean, 17.2 +/- 4.8 years; range, 15
      21.2 years). RESULTS: The mean Knee Society function and knee scores were
      comparable in the two groups. Radiographically, the number of overcorrections and
      the number of radiolucencies were statistically higher in the mobile-bearing
      group (69% versus 24%). At final followup, considering revision for any reason,
      12 of 77 (15%) UKAs were revised (for aseptic loosening, dislocation, and
      arthritis progression) in the mobile-bearing group and 10 of 79 (12%) in the
      fixed-bearing group (for wear and arthritis progression). CONCLUSIONS: This long
      term study did not demonstrate any difference in survivorship between fixed and
      mobile-bearing but pointed out specific modes of failure.

PMID- 21732025
TI  - The classic: Delta shoulder prosthesis for rotator cuff rupture. 1993.

PMID- 21732026
TI  - Arthroscopic scapholunate joint reduction. Is an effective treatment for
      irreparable scapholunate ligament tears?
AB  - BACKGROUND: Irreparable tears to the scapholunate (SL) interosseous ligament area
      are common causes of mechanical wrist pain and yet treatment of this condition
      remains challenging. The reduction association of the SL joint (RASL) technique
      alleviates pain while preserving wrist function by creating a fibrous
      pseudarthrosis stabilized by a cannulated screw placed through the SL joint.
      Although arthroscopic RASL (ARASL) is a minimally invasive alternative to the
      open procedure, its effectiveness in controlling pain and preserving wrist
      function has not been established. QUESTIONS/PURPOSES: To determinate whether
      ARASL was obtained relieve pain and restore function to the wrist. PATIENTS AND
      METHODS: We reviewed eight patients (nine wrists) who had ARASL for SL
      instability with a reducible SL ligament tear (chronic lesion) from 2005 to 2009.
      Seven of eight were males and mean age was 44.5 years (range, 38-56 years). We
      recorded pain using a scale, the Disabilities of the Arm, Shoulder and Hand
      (DASH) score, grip strength, and range of motion (ROM). Minimum followup was 12
      months (mean, 34.6 months; range, 12-43 months). RESULTS: The visual analog pain
      score was rated 5.4 (range, 0-10) preoperatively and 1.5 (1-3) after ARASL.
      Postoperative grip strength of the wrist was 78% of the contralateral, unaffected
      wrist. The average postoperative wrist ROM was to 107 degrees , 20% less than the
      preoperative ROM. The SL angle decreased from 70.5 degrees  to 59.3 degrees . In
      three cases, screws were removed owing to loosening or symptoms. CONCLUSIONS: Our
      preliminary observations suggest ARASL for treating irreparable SL ligament tear
      is feasible, controls pain, and improves wrist function while preserving ROM.
      Larger series with longer followup are required to confirm our observations.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21732027
TI  - A simplified method to determine left atrial volume and transport function using
      multi-slice computed tomography in patients with atrial fibrillation: comparison
      with transthoracic echocardiography.
AB  - Although left atrial volumes (LAVs) and transport function can be accurately
      measured by multi-slice computed tomography (MSCT) during sinus rhythm, limited
      data are available for in patients with atrial fibrillation (AF). The aims of our
      study were to compare LAVs and function assessed by MSCT and transthoracic
      echocardiography (TTE) during AF, and to validate a simplified method to
      determine LAVs and functions using MSCT. A total of 150 consecutive AF patients
      who were scheduled to undergo catheter ablation were enrolled in this study. All
      subjects underwent MSCT and TTE on the same day. LAVs were measured by MSCT at
      every 10% of the R-R interval (10-phase analysis). LA transport function was
      assessed by measuring changes in LAVs. LAVs and functions were also assessed by
      TTE using a modified Simpson's method and an area-length method. Fifty patients
      were in sinus rhythm (SR) and 100 were in AF during their examinations. Although
      TTE underestimated the maximal LAV (LAV(max), by 38.3%) and overestimated the
      total LA emptying fraction (LAEF(total), by 61.1%) compared with MSCT, there were
      excellent correlations between TTE and MSCT. LAV(max) and the minimal LAV
      (LAV(min)) based on MSCT were determined at relatively constant cardiac phases
      during AF as well as SR (LAV(max); 40%, LAV(min); 100% of R-R interval, fixed
      phase analysis). LAVs and LAEF(total) assessed by 10-phase analysis showed good
      correlations with those assessed by fixed-phase analysis (P < 0.001). LAVs and
      function assessed by MSCT correlated well with LAVs and functions assessed by
      TTE, irrespective of the underlying rhythm. Our results indicate that in the
      context of MSCT, fixed-phase analysis is a simple and reliable method to
      determine LAVs and function in patients with AF.

PMID- 21732028
TI  - Gender-based prognostic value of pharmacological cardiac magnetic resonance
      stress testing: head-to-head comparison of adenosine perfusion and dobutamine
      wall motion imaging.
AB  - This study evaluated the gender related long-term prognostic value of adenosine
      perfusion and dobutamine wall motion imaging as assessed during a combined single
      session stress cardiac magnetic resonance (CMR) examination. In 717 patients a
      combined CMR stress examination was performed. Inducible perfusion deficits and
      wall motion abnormalities were identified visually. Clinical parameters were
      assessed at the time of the CMR examination. All patients were contacted to
      determine the occurrence of hard cardiac events (cardiac death, myocardial
      infarction) during a median follow-up period of 5.3 years. A complete combined
      CMR examination and follow-up data were available in 679 patients (471 men). A
      total of 77 hard cardiac events (63 in men) occurred during follow-up.
      Multivariate analysis revealed the presence of inducible perfusion deficits or
      wall motion abnormalities as independent predictors of hard cardiac events for
      both gender with an incremental value over conventional cardiovascular risk
      factors. In case of a negative stress test result, event-free survival was 100%
      in women for 4 years and >99% in men for 2 years after the CMR examination. CMR
      perfusion and wall motion testing are equally suited for cardiac risk
      stratification in men and women. Stress CMR negative women exhibited very low
      event rates up to 4 years following the examination, while in men annual event
      rates increased after the second year. Consequently, the generally proposed 2
      year warranty period of non-invasive stress testing may be prolonged to a 4 year
      level in CMR stress testing negative women.

PMID- 21732029
TI  - Scintigraphic spectrum of a patient population with suspected arrhythmogenic
      right ventricular dysplasia.
AB  - Gated radionuclide ventriculography (RNV), combined with inter- and
      intraventricular dyssynchrony measurement by phase analysis, is able to evidence
      right and left ventricular mechanical cardiac disorders and may contribute to the
      diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). Nevertheless, the
      patients referred for suspicion of ARVD on the basis of symptoms, electrical
      abnormalities or family history of sudden death, are very heterogeneous and the
      examination findings spread out from strictly normal to severely abnormal. In
      order to describe the patient population encountered in "real life" we propose to
      use an automatic clustering method based on RNV results in order to segment the
      overall population into subgroups with coherent scintigraphic data in each one. A
      series of 130 consecutive patients presenting with various criteria suggestive of
      ARVD has been studied over a 3-year period. Seven variables have been extracted
      from gated RNV: left and right ejection fractions, visual semi-quantitative
      assessment of left and right ventricular volumes, left and right phase standard
      deviations and inter-ventricular dyssynchrony (IVD) measured from the phase
      histograms. The Self Organizing Map (SOM) clustering method has been applied to
      these data with various numbers of variables (right ventricular values only or
      values from both ventricles) and an increasing number of classes from two to
      nine. Including left ventricular variables and IVD in the analysis results in
      significant changes in classification compared to right ventricular data alone.
      Clustering into nine classes seems to be the most pertinent one and separates
      patients into four groups of normal result or insignificant left, right or
      bilateral abnormalities, two groups of isolated right ventricular abnormalities
      of increasing severity and three groups of severe bilateral abnormalities, right
      predominant with and without IVD, and left predominant. Automatic clustering of
      patients on the basis of scintigraphic results helps to understand the
      signification of the large spectrum of results encountered in clinical practice
      for patients whose common characteristic is to present some abnormalities or risk
      factors leading to investigations in the context of suspicion of ARVD. Although
      the final diagnosis remains questionable in a large proportion of patients, the
      knowledge of the various profiles of gated blood pool phase analysis may help for
      stratification of patients at risk of ARVD.

PMID- 21732030
TI  - Left ventricular cavity obliteration during dobutamine stress echocardiography in
      diabetic patients.
AB  - Prevalence of dynamic left ventricular outflow tract obstruction (DLVO) during
      dobutamine stress-echo (DSE) seems disproportionally high among diabetic
      patients. We retrospectively identified 212 diabetic (D+) and 212 non diabetic (D
      ) subjects, who underwent DSE for suspected coronary artery disease (CAD); we
      evaluated DSE-induced DLVO prevalence and correlates. During DSE, 105 patients in
      D+ (50%) and 83 in D- group (39%, P = 0.032) developed a DLVO, with similar
      maximum gradient (94 +/- 49 mmHg in D+ vs. 86 +/- 49 mmHg in D-, P = NS). D+ and
      D- patients with DLVO showed reduced LV end-diastolic and end-systolic dimension.
      Compared with diabetic subjects without DLVO, diabetic patients with DLVO had
      higher left ventricular (LV) ejection fraction (EF), lower LV mass index;
      diastolic function was normal in a higher proportion of cases. Non diabetic
      patients with moderate or severe DLVO had higher LV EF compared with patients
      without DLVO. At multivariate analysis, in D+ patients, the only independent
      predictor was a smaller LV end-diastolic diameter (HR 0.779, CI 0.655-0.926, P =
      0.005); in D- patients lower age (HR 0.878, CI 0.806-0.957, P = 0.003), higher LV
      EF (HR 1.087, CI 1.003-1.177, P = 0.042) and lower peak WMSI (HR 0.017, CI 0.001
      0.325, P = 0.007) were associated to presence of DLVO. In D+ patients, during a
      median follow-up of 924 +/- 134 days, we observed 11 new cardiac events, only 1
      in patients with DLVO (P = 0.0041). DSE-provoked DLVO had a very high prevalence
      in patients evaluated for suspected CAD, especially among diabetic patients;
      echocardiographic predictors were a reduced LV dimension in D+ and a preserved
      systolic function, both at rest and at peak stress, in D- patients.

PMID- 21732031
TI  - Investigating the impact of mindfulness meditation training on working memory: a
      mathematical modeling approach.
AB  - We investigated whether mindfulness training (MT) influences information
      processing in a working memory task with complex visual stimuli. Participants
      were tested before (T1) and after (T2) participation in an intensive one-month MT
      retreat, and their performance was compared with that of an age- and education
      matched control group. Accuracy did not differ across groups at either time
      point. Response times were faster and significantly less variable in the MT
      versus the control group at T2. Since these results could be due to changes in
      mnemonic processes, speed-accuracy trade-off, or nondecisional factors (e.g.,
      motor execution), we used a mathematical modeling approach to disentangle these
      factors. The EZ-diffusion model (Wagenmakers, van der Maas, & Grasman,
      Psychonomic Bulletin & Review 14:(1), 3-22, 2007) suggested that MT leads to
      improved information quality and reduced response conservativeness, with no
      changes in nondecisional factors. The noisy exemplar model further suggested that
      the increase in information quality reflected a decrease in encoding noise and
      not an increase in forgetting. Thus, mathematical modeling may help clarify the
      mechanisms by which MT produces salutary effects on performance.

PMID- 21732032
TI  - Streptomyces shenzhenensis sp. nov., a novel actinomycete isolated from mangrove
      sediment.
AB  - An actinomycete strain, which was designated 172115(T), was isolated from
      mangrove soil in Shenzhen, China. Strain 172115(T) fell within the genus
      Streptomyces in the 16S rRNA gene tree and could be grouped into this genus based
      on its chemotaxonomic and morphological data. The strain shared the highest 16S
      rRNA gene sequence similarities with Streptomyces lanatus NBRC 12787(T)
      (AB184845) (98.29%) and Streptomyces lucensis NBRC 13056(T) (AB184280) (98.26%).
      The DNA-DNA hybridization values between strain 172115(T) and the two most
      closely related type strains were low enough to justify the assignment of the
      strain to a novel species. On the basis of these phenotypic, phylogenetic and
      chemotaxonomic characteristics, 172115(T) represents a novel species of the genus
      Streptomyces, for which, the name Streptomyces shenzhenensis sp. nov. is proposed
      for strain 172115(T) (=CCTCC AA 2011001(T)=DSM 42034(T)).

PMID- 21732033
TI  - Physiological diversity within the Kluyveromyces marxianus species [corrected].
AB  - The Kluyveromyces marxianus strains CBS 6556, CBS 397 and CBS 712(T) were
      cultivated on a defined medium with either glucose, lactose or sucrose as the
      sole carbon source, at 30 and 37 degrees C. The aim of this work was to evaluate
      the diversity within this species, in terms of the macroscopic physiology. The
      main properties evaluated were: intensity of the Crabtree effect, specific growth
      rate, biomass yield on substrate, metabolite excretion and protein secretion
      capacity, inferred by measuring extracellular inulinase activity. The strain
      Kluyveromyces lactis CBS 2359 was evaluated in parallel, since it is the best
      described Kluyveromyces yeast and thus can be used as a control for the
      experimental setup. K. marxianus CBS 6556 presented the highest specific growth
      rate (0.70 h(-1)) and the highest specific inulinase activity (1.65 U mg(-1) dry
      cell weight) among all strains investigated, when grown at 37 degrees C with
      sucrose as the sole carbon source. The lowest metabolite formation and highest
      biomass yield on substrate (0.59 g dry cell weight g sucrose(-1)) was achieved by
      K. marxianus CBS 712(T) at 37 degrees C. Taken together, the results show a
      systematic comparison of carbon and energy metabolism among three of the best
      known K. marxianus strains, in parallel to K. lactis CBS 2359.

PMID- 21732034
TI  - Granaticins and their biosynthetic gene cluster from Streptomyces vietnamensis:
      evidence of horizontal gene transfer.
AB  - Streptomyces vietnamensis, a recently designated species isolated from tropical
      forest soil, was found to be a new granaticin producer. The granaticin
      biosynthetic gene cluster (gra) and flanking genes from S. vietnamensis were
      cloned and sequenced by a sequential cloning strategy. All biosynthetic genes
      were found as expected. The high overall homology of the gra cluster from S.
      vietnamensis to that of Streptomyces violaceoruber Tu22 indicated a recent common
      ancestor of the two clusters. However, a flanking gene orf35 was missing from the
      gra cluster of S. vietnamensis, and high frequency of insertions and deletions of
      short fragment (shorter than 63 bp) were observed throughout the sequenced region
      compared to that of S. violaceoruber Tu22. These revealed a rapid evolution of
      the gra cluster and suggested that small insertions and deletions might be one of
      the basic evolution mechanisms for streptomycete genomes. The phylogenetic
      incongruence between 16S rDNA and the gra cluster and the scattered distribution
      of the granaticin producers within Streptomyces implicated horizontal gene
      transfer (HGT) being involved in the gra cluster dispersion. The remnants of
      orf35 found in S. vietnamensis present a scenario on how the antibiotic gene
      clusters evolved after HGT. The contemporary gra cluster residing in S.
      vietnamensis could be interpreted as a combination of HGT and highly variable
      vertical transmission.

PMID- 21732035
TI  - Cyanobacteria-mediated phenylpropanoids and phytohormones in rice (Oryza sativa)
      enhance plant growth and stress tolerance.
AB  - Phenylpropanoids, flavonoids and plant growth regulators in rice (Oryza sativa)
      variety (UPR 1823) inoculated with different cyanobacterial strains namely
      Anabaena oryzae, Anabaena doliolum, Phormidium fragile, Calothrix geitonos,
      Hapalosiphon intricatus, Aulosira fertilissima, Tolypothrix tenuis, Oscillatoria
      acuta and Plectonema boryanum were quantified using HPLC in pot conditions after
      15 and 30 days. Qualitative analysis of the induced compounds using reverse phase
      HPLC and further confirmation with LC-MS/MS showed consistent accumulation of
      phenolic acids (gallic, gentisic, caffeic, chlorogenic and ferulic acids),
      flavonoids (rutin and quercetin) and phytohormones (indole acetic acid and indole
      butyric acid) in rice leaves. Plant growth promotion (shoot, root length and
      biomass) was positively correlated with total protein and chlorophyll content of
      leaves. Enzyme activity of peroxidase and phenylalanine ammonia lyase and total
      phenolic content was fairly high in rice leaves inoculated with O. acuta and P.
      boryanum after 30 days. Differential systemic accumulation of phenylpropanoids in
      plant leaves led us to conclude that cyanobacterial inoculation correlates
      positively with plant growth promotion and stress tolerance in rice. Furthermore,
      the study helped in deciphering possible mechanisms underlying plant growth
      promotion and stress tolerance in rice following cyanobacterial inoculation and
      indicated the less explored avenue of cyanobacterial colonization in stress
      tolerance against abiotic stress.

PMID- 21732036
TI  - Clinical utility of the neutrophil distribution pattern obtained using the CELL
      DYN SAPPHIRE hematology analyzer for the diagnosis of myelodysplastic syndrome.
AB  - We evaluated the diagnostic utility of peripheral blood neutrophil distribution
      patterns obtained using the CELL-DYN SAPPHIRE hematology analyzer in patients
      with myelodysplastic syndrome (MDS). Peripheral blood was obtained from 467
      individuals including 32 patients with MDS, and the respective neutrophil
      distribution patterns were observed using two light scatters [7-degree complexity
      (7D) and 90-degree lobularity (90D)]. These scattering intensities are shown as
      median (median neutrophil distribution: MND) and coefficient of variation
      (neutrophil distribution width: NDW). Generally, MDS patients showed lower 7D
      MND, higher 7D NDW, lower 90D MND and higher 90D NDW than other comparable
      groups. Whereas 90D parameters were more diagnostically efficient than 7D ones in
      patients with MDS. The sensitivity and specificity of 90D MND for MDS patients
      became 78.1 and 78.9%, respectively (cut-off value = 14,514). 90D NDW was most
      diagnostically effective with 87.5% sensitivity and 91.0% specificity (cut-off
      value = 21.2%). Both 90D parameters showed no evident correlation with the degree
      of either leukocytopenia or peripheral blood dysgranulopoiesis. In conclusion,
      neutrophil distribution parameters, especially 90D NDW, appear to provide
      convenient and objective markers for the screening of patients with MDS in
      routine laboratory hematology.

PMID- 21732037
TI  - Induction therapy using the MRC UKALLXII/ECOG E2993 protocol in Chinese adults
      with acute lymphoblastic leukemia.
AB  - Patients with newly diagnosed acute lymphoblastic leukemia (ALL) at a single
      institution were analyzed retrospectively. From 2006 to 2010, 47 patients were
      treated using the MRC UKALLXII/ECOG E2993 protocol. Prior to July 2005, 40
      patients had been treated with the JALSG ALL 87 protocol. A complete remission
      (CR) rate of 91.5% was achieved with the E2993 protocol, which was not
      significantly higher than the 80% achieved using JALSG (P > 0.05). The median
      duration of CR in months was 19 for all patients treated with the MRC
      UKALLXII/ECOG E2993 protocol. Ph+ patients showed a median CR duration of 11.5
      months, while Ph- patients had a significantly longer CR duration of 19 months (P
      = 0.019). Further, Ph- patients at standard risk (stratified on the basis of age
      and white blood cell count at diagnosis) had a CR duration of 21 months, which
      was significantly longer than the 12-month CR duration for the ten Ph- patients
      at high risk (P = 0.001). Significant differences were found in the 2-year event
      free survival and overall survival rates between the MRC UKALLXII/ECOG E2993 and
      JALSG ALL 87 groups in the following three cohorts: all patients (P = 0.009 and
      0.022, respectively), Ph- patients (P = 0.009 and 0.018, respectively), and
      standard-risk patients (P = 0.014 and 0.007, respectively). The overall mortality
      rate for induction therapy in the MRC UKALLXII/ECOG E2993 group was 2.1% (1 of 47
      patients). One or more instances of grade IV myelosuppression occurred during
      induction therapy. Among the non-hematological toxicities, alopecia and elevated
      ALT and AST levels were the most common. The levels of ALT and AST could be
      reduced to less than twofold the normal values within 1-2 weeks. The data
      indicate that the MRC UKALLXII/ECOG E2993 regimen is well tolerated in Chinese
      adults with ALL and can improve survival compared with the JALSG ALL 87 protocol.
      Risk stratification at diagnosis based on age and WBC count is suitable for
      adults with ALL, and it is necessary to adopt different strategies as determined
      by diagnostic results. Lastly, Ph+ patients have an extremely poor prognosis.

PMID- 21732038
TI  - Vascular endothelial growth factor-C and its receptor type-3 expressed in acute
      lymphocytic leukemia cases with t(1;19).
AB  - The vascular endothelial growth factor (VEGF)-C system was analyzed in two cases
      of acute lymphocytic leukemia (ALL) with TCF3/PBX1 fusion to determine whether
      the VEGF-C system influences the growth of these ALL blasts. Bone marrow non
      adherent mononuclear cells were prepared from the patients, and expressions of
      VEGFs and VEGF receptors (VEGFRs) were analyzed based on RNA and protein levels.
      Cell proliferation was also assayed with or without neutralizing antibodies to
      VEGFs. The patients' leukemic blasts expressed a significant amount of VEGF-C and
      VEGFR type-3. When anti-VEGF-C antibody was added to the blast cell cultures,
      cell proliferation was suppressed. These observations indicate that, in our ALL
      cases with TCF3/PBX1 fusion, VEGF-C autocrine stimulation plays an important role
      in the proliferation of ALL.

PMID- 21732039
TI  - Pharmacologic strategies for the prevention of stroke in patients with atrial
      fibrillation.
AB  - OPINION STATEMENT: Stroke is a dreaded complication of atrial fibrillation. In
      the past, preventive therapy included aspirin and oral anticoagulation. Selected
      patients who are not suitable for oral anticoagulation may benefit from the
      addition of clopidogrel with aspirin. This combination, when compared with
      aspirin, offers a reduced risk of stroke at a cost of more major bleeding. We use
      this therapy in patients with atrial fibrillation who have unstable coronary
      syndromes or in patients who receive coronary artery stents who are not good
      candidates for "triple therapy" with aspirin, clopidogrel, and warfarin. The
      duration of therapy is tempered by many variables. In the case of coronary
      stents, we ask the interventionalist to consider a bare metal stent to shorten
      the duration of need for clopidogrel plus aspirin. After several months of
      combination therapy, we stop this therapy and begin warfarin therapy. Dabigatran
      is commercially available in the United States. In patients who have difficult to
      control International Normalized Ratio (INR) values or who do not wish to have
      regular coagulation monitoring, dabigatran offers a huge advantage. The benefit
      seems less if the INR is consistently within range. We are impressed with the
      superior reduction in stroke and systemic embolism with 150 mg of dabigatran
      twice daily compared to warfarin and also its low risk of intracranial
      hemorrhage. The results of clinical trials involving factor Xa agents are now
      being presented. How these agents fit into the marketplace remains to be seen but
      they will offer clinicians additional therapy for stroke prevention in atrial
      fibrillation.

PMID- 21732040
TI  - Accelerated BMIPP uptake immediately after reperfused ischemia in the isolated
      rat heart model.
AB  - OBJECTIVE: 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) can visualize
      myocardial fatty acid metabolism and has extensive potential for diagnosing
      cardiac diseases such as acute coronary syndrome in the clinical setting.
      Increased BMIPP uptake with decreased perfusion occasionally occurs under acute
      reperfusion ischemia and the kinetics of BMIPP remain unclear. The present study
      uses the isolated rat heart model to measure kinetic changes in BMIPP under acute
      reperfusion ischemia. METHODS: Male Wistar rats were allotted to normal control
      (NG), mild (MG) and severe (SG) ischemia groups. The hearts were perfused
      according to the Langendorff method at a constant flow rate, and BMIPP wash-in
      and wash-out were studied. No-flow ischemia was applied for 15 and 30 min to the
      MG and SG groups, followed immediately by the wash-in and wash-out study. Whole
      heart radioactivity was determined using an external gamma detector throughout
      the experiment. Rates of myocardial uptake (K1, mL/min) and clearance (k2, min(
      1)) were generated using a compartmental model analysis. The same procedures and
      protocols were performed using (99m)Tc-sestamibi (MIBI) as a perfusion study.
      RESULTS: Perfusion pressure significantly increased and mean heart rate
      significantly decreased in the severe ischemia group (heart rate: 244 +/- 76, 304
      +/- 105 and 94 +/- 140 bpm; perfusion pressure: 67 +/- 13, 101 +/- 31 and 160 +/-
      84 mmHg for NG, MG and SG, respectively). MIBI-K1 significantly decreased,
      whereas BMIPP-K1 increased in the MG and SG groups (MIBI-K1: 3.45 +/- 1.10, 1.95
      +/- 0.82, and 1.05 +/- 0.13 mL/min; BMIPP-K (1): 3.06 +/- 0.88, 3.91 +/- 0.87,
      and 4.94 +/- 1.51 mL/min for NG, MG and SG, respectively) with an inverse
      relationship to the severity of ischemia. MIBI-k2 increased markedly in severe
      ischemia (NG vs. MG: p < 0.05), whereas BMIPP-k2 did not change in the ischemic
      groups (MIBI-k2: 0.00072 +/- 0.0011, 0.00038 +/- 0.00076 and 0.043 +/- 0.033;
      BMIPP-k2: 0.0056 +/- 0.0028, 0.0029 +/- 0.0010 and 0.0037 +/- 0.0022 min(-1) for
      NG, MG and SG, respectively). CONCLUSION: Myocardial BMIPP uptake increased
      immediately upon reperfusion after no-flow ischemia, and was inversely related to
      the severity of ischemia. The increased uptake was not due to reduced clearance,
      but to accelerated extraction.

PMID- 21732041
TI  - Cell division and aging of the organism.
AB  - The capacity to regenerate cell compartments through cell proliferation is an
      important characteristic of many developed metazoan tissues. Pre- and post-natal
      development proceeds through the modifications occurring during cell division.
      Experiments with cultivated cells showed that cell proliferation originates
      changes in cell functions and coordinations that contribute to aging and
      senescence. The implications of the finite cell proliferation to aging of the
      organism is not the accumulation of cells at the end of their life cycle, but
      rather the drift in cell function created by cell division. Comparative
      gerontology shows that the regulation of the length of telomeres has no
      implications for aging. On the other hand there are interspecies differences in
      regard to the somatic cell division potential that seem to be related with the
      "plasticity" of the genome and with longevity, which should be viewed
      independently of the aging phenomenon. Telomeres may play a role in this
      plasticity through the regulation of chromosome recombination, and via the latter
      also in development.

PMID- 21732042
TI  - Distinct hepatic lipid profile of hypertriglyceridemic mice determined by easy
      ambient sonic-spray ionization mass spectrometry.
AB  - Easy ambient sonic-spray ionization mass spectrometry (EASI-MS) was used to
      interrogate the hepatic lipid profiles of hypertriglyceridemic and control
      normotriglyceridemic mice. The analyses of ex vivo complex lipid mixtures were
      made directly with EASI-MS without accompanying separation steps. Intense ions
      for phosphatidylcholines and triacylglycerols were observed in the positive ion
      mode whereas the spectra in the negative ion mode provided profiles of
      phosphatidylethanolamines and phosphatidylinositol. EASI-MS was coupled to high
      performance thin-layer chromatography for analysis of free fatty acids. Fourier
      transform-ion cyclotron resonance-mass spectrometry was also employed to confirm
      the identity of the detected lipids. We demonstrated higher incorporation of
      oleic acid in phosphatidylcholine and triacylglycerol composition, higher
      relative abundance of arachidonic acid containing phosphatidylinositol, and
      overall distinct free fatty acid profile in the livers of genetic
      hypertriglyceridemic mice. We propose that these alterations in liver lipid
      composition are related to the higher tissue and body metabolic rates described
      in these hypertriglyceridemic mice.

PMID- 21732043
TI  - Development of a simple gel permeation clean-up procedure coupled to a rapid
      disequilibrium enzyme-linked immunosorbent assay (ELISA) for the detection of
      Sudan I dye in spices and sauces.
AB  - Sudan dyes have been found to be added to chilli and chilli products for illegal
      colour enhancement purposes. Due to the possible carcinogenic effect, they are
      not authorized to be used in food in the European Union or the USA. However, over
      the last few years, many products imported from Asian and African countries have
      been reported via the Rapid Alert System for Food and Feed in the European Union
      to be contaminated with these dyes. In order to provide fast screening method for
      the detection of Sudan I (SI), which is the most widely abused member of Sudan
      dyes family, a unique (20 min without sample preparation) direct disequilibrium
      enzyme-linked immunosorbent assay (ELISA) was developed. The assay was based on
      polyclonal antibodies highly specific to SI. A novel, simple gel permeation
      chromatography clean-up method was developed to purify extracts from matrices
      containing high amounts of fat and natural pigments, without the need for a large
      dilution of the sample. The assay was validated according to the Commission
      Decision 2002/657/EC criteria. The detection capability was determined to be 15
      ng g(-1) in sauces and 50 ng g(-1) in spices. The recoveries found ranged from
      81% to 116% and inter- and intra-assay coefficients of variation from 6% to 20%.
      The assay was used to screen a range of products (85 samples) collected from
      different retail sources within and outside the European Union. Three samples
      were found to contain high amounts (1,649, 722 and 1,461 ng g(-1)) of SI by
      ELISA. These results were confirmed by liquid chromatography-tandem mass
      spectrometry method. The innovative procedure allows for the fast, sensitive and
      high throughput screening of different foodstuffs for the presence of the illegal
      colorant SI.

PMID- 21732044
TI  - Identification and characterization of impurities of tetracosactide by capillary
      electrophoresis and liquid chromatography coupled to time-of-flight mass
      spectrometry.
AB  - Tetracosactide is a synthetic peptide analogue of the human adrenocorticotropic
      hormone that stimulates the production of cortisol in the adrenal cortex. The
      medical use of the compound is primarily the diagnosis of the adrenal cortex
      function. In order to characterize impurities of the drug, tetracosactide samples
      were analysed by both liquid chromatography and capillary electrophoresis coupled
      to a quadrupole time-of-flight mass spectrometer. The identification of the
      impurities was carried out based on accurate mass determination and fragment ion
      spectra. The presence of several peptides of lower and higher masses than
      tetracosactide could be shown, including N- and C-terminally truncated peptides
      as well as peptides which still contained protecting groups or additional amino
      acids. Furthermore, a semi-quantitative estimation of the relative amounts of the
      impurities in different samples as well as a commercial preparation revealed that
      the number and the type of the impurities varied between the samples. Comparing
      the selectivity of liquid chromatography and capillary electrophoresis regarding
      the separation of tetracosactide impurities, it can be stated that capillary
      electrophoresis showed a higher suitability for the separation of tetracosactide
      fragments (smaller peptides) while the larger peptides, i.e. those wearing
      protecting groups, were separated more efficiently by liquid chromatography.

PMID- 21732045
TI  - Long-term therapy with intravenous immunoglobulin is beneficial in patients with
      autoimmune diseases.
AB  - The objective of our study is to evaluate the clinical response, steroid-sparing
      and adverse affects of long-term intravenous immunoglobulin (IVIG) treatment for
      autoimmune diseases. Patients were recruited from the Rheumatology clinic. All
      patients fulfilled the ACR criteria for the appropriate autoimmune disease.
      Beneficial effects of IVIG therapy in systemic lupus erythematosus (SLE) patients
      were evaluated utilizing the SLEDAI score. Clinical remission in patients with
      other autoimmune diseases was evaluated by a rheumatologist. Data were retrieved
      retrospectively from an IVIG database (Excel program). Seventeen patients-SLE (n
      = 11) and other autoimmune diseases (n = 6)-received a high dose IVIG protocol
      monthly for 6 months, followed by therapy every 2-3 months. The patients received
      a mean of 7.9 courses/patient. The mean follow-up for long-term therapy was 30
      months. The response to IVIG treatment was remission in 12 patients. Change in
      the SLEDAI score following IVIG therapy was significant (p < 0.05). In
      responders, IVIG harbored a significant steroid-sparing effect (p < 0.05). Mild
      and transient adverse effects persisted with long-term therapy in 50% of
      patients. Severe adverse effects (pulmonary embolism and seizures) occurred early
      in two patients with SLE and secondary anti-phospholipid syndrome. Long-term IVIG
      therapy is beneficial and carries a good safety profile for SLE and other
      autoimmune diseases.

PMID- 21732046
TI  - Antibiotic therapy in neonatal and pediatric septic shock.
AB  - Severe sepsis accounts for nearly 4,500 deaths (mortality rate 10%), and is
      responsible for nearly $2 billion annual healthcare expenditure in the United
      States. Early and speedy treatment of critically ill septic patients can halt or
      reduce the likelihood of physiologic progression to multi-system organ failure. A
      cornerstone of this therapeutic strategy is antibiotic administration. In this
      review, we discuss the empirical treatment strategies for the treatment of early
      and late neonatal sepsis, along with pediatric sepsis. Furthermore, we discuss
      the rationale that underlies the adoption of such treatment strategies. The
      present article also discusses the emergence of multi-drug organisms as the
      causative agents for sepsis, i.e. methicillin-resistant Staphylococcus aureus
      (MRSA), resistant enterococci and Klebsiella pneumoniae carbapenemases (KPC).

PMID- 21732047
TI  - Immunohistochemical assessment of intrinsic and extrinsic markers of hypoxia in
      reproductive tissue: differential expression of HIF1alpha and HIF2alpha in rat
      oviduct and endometrium.
AB  - Hypoxia is thought to be critical in regulating physiological processes within
      the female reproductive system, including ovulation, composition of the fluid in
      the oviductal/uterine lumens and ovarian follicle development. This study
      examined the localisation of exogenous (pimonidazole) and endogenous [hypoxia
      inducible factor 1alpha and 2alpha (HIF1alpha, -2alpha), glucose transporter type
      1 (GLUT1) and carbonic anhydrase 9 (CAIX)] hypoxia-related antigens within the
      oviduct and uterus of the rat reproductive tract. The extent to which each
      endogenous antigen co-compartmentalised with pimonidazole was also assessed.
      Female Wistar Furth rats (n = 10) were injected intraperitoneally with
      pimonidazole (60 mg/kg) 1 h prior to death. Reproductive tissues were removed
      immediately following death and fixed in 4% paraformaldehyde before being
      embedded in paraffin. Serial sections were cut (6-7 MUm thick) and antigens of
      interest identified using standard immunohistochemical procedures. The mucosal
      epithelia of the ampulla, isthmus and uterus were immunopositive for pimonidazole
      in most sections. Co-compartmentalisation of pimonidazole with HIF1alpha was only
      expressed in the mucosa of the uterus whilst co-compartmentalisation with
      HIF2alpha was observed in the mucosa of the ampulla, isthmus and uterus. Both
      GLUT1 and CAIX were co-compartmentalised with pimonidazole in mucosa of the
      isthmus and uterus. This study confirms that mucosal regions of the rat oviduct
      and uterus frequently experience severe hypoxia and there are compartment
      specific variations in expression of endogenous hypoxia-related antigens,
      including the HIF isoforms. The latter observation may relate to target gene
      specificity of HIF isoforms or perhaps HIF2alpha's responsiveness to non-hypoxic
      stimuli such as hypoglycaemia independently of HIF1alpha.

PMID- 21732048
TI  - Risk of lung cancer in relation to contiguous windows of endotoxin exposure among
      female textile workers in Shanghai.
AB  - OBJECTIVE: Exposure to endotoxin has been consistently associated with a reduced
      risk of lung cancer. However, there is a paucity of information regarding
      temporal aspects of this relationship. The objective of this study was to
      investigate the associations between contiguous windows of endotoxin exposure and
      risk of lung cancer. METHODS: Data were reanalyzed from a case-cohort study (602
      cases, 3,038 subcohort) of female textile workers in Shanghai, China. Cumulative
      endotoxin exposure was partitioned into two windows: >=20 and <20 years before
      risk. Exposure-response relations were examined using categorical and non-linear
      (semi-parametric) models, accounting for confounding by previous exposure
      windows. RESULTS: There was an inverse trend of decreasing risk of lung cancer
      associated with increasing levels of endotoxin exposure >=20 years before risk (p
      trend = 0.02). Women in the highest two categories of cumulative exposures had
      hazard ratios of 0.78 (95% CI 0.60-1.03) and 0.77 (95% CI 0.58-1.02) for lung
      cancer, respectively, in comparison with unexposed textile workers. There was,
      however, a weaker association and not statistically significant between lung
      cancer and endotoxin exposure accumulated in the more recent window (<20 years
      before risk). CONCLUSION: Results provide further evidence that endotoxin
      exposure that occurred 20 years or more before risk confers the strongest
      protection against lung cancer, indicating a possible early anti-carcinogenic
      effect. Further studies are needed to better understand the underlying biological
      mechanisms for this effect.

PMID- 21732049
TI  - Mediators and moderators of the effects of a year-long exercise intervention on
      endogenous sex hormones in postmenopausal women.
AB  - OBJECTIVE: To identify factors that mediate or moderate the effects of exercise
      on postmenopausal sex hormone concentrations. METHODS: Postmenopausal women were
      randomized to 12 months of aerobic exercise for 200 min/week (n = 160) or to a
      control group (n = 160). Intention-to-treat analyses were performed using general
      linear models with sex hormone concentrations at 6 and 12 months as the outcome.
      Mediation by adiposity and insulin was investigated by examining changes in
      effect estimates after adjustment for changes in these factors over 12 months.
      Moderation was studied as the interaction between group assignment and eight
      baseline characteristics. RESULTS: Intervention effects on sex hormone-binding
      globulin (SHBG) and estradiol changes were attenuated with adjustment for change
      in overall body fat, while there was less attenuation adjusting for intra
      abdominal fat change. Intervention effects on SHBG levels were unaffected by
      adjustment for insulin change. Significant interactions were identified between
      treatment and physical fitness (for SHBG and testosterone) and age (for
      testosterone), implying subgroup differences in intervention effect. CONCLUSIONS:
      Our data suggest that overall fat loss partially mediated exercise-induced
      changes in estradiol and SHBG concentrations. No previous RCT in postmenopausal
      women has studied moderators of exercise-induced sex hormone changes; therefore,
      future studies are needed to corroborate our results.

PMID- 21732050
TI  - Cytophagic histiocytic panniculitis with haemophagocytosis in a patient with
      familial multiple lipomatosis and review of the literature.
AB  - We report a patient with the extremely rare familial multiple lipomatosis
      syndrome, who developed the uncommon autoimmune disease cytophagic histiocytic
      panniculitis, manifested as inflammation of preexisting lipomas. Despite his
      initial critical condition and unsuccessful treatment with steroids, he responded
      to cyclosporin and remains well 15 years after diagnosis. In contrast with most
      previous reports, our patient stays dependent on cyclosporin; repeated attempts
      of discontinuing or substituting treatment were quickly followed by relapse.
      Haemophagocytic panniculitis is considered as a T-cell disorder, but its exact
      pathophysiological mechanism has not been clarified. Differential diagnosis of
      cytophagic histiocytic panniculitis mainly includes malignant histiocytosis,
      subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus
      panniculitis (lupus profundus). We discuss the main clinical features, diagnostic
      challenges and treatment issues of this usually benign, but at times life
      threatening autoimmune condition.

PMID- 21732051
TI  - Anti-citrullinated protein antibodies (ACPA) in early rheumatoid arthritis.
AB  - Autoantibodies with the highest specificity for rheumatoid arthritis (RA) are the
      antibodies directed to citrulline-containing epitopes, so-called anti
      citrullinated peptide/protein antibodies (ACPA). During the past decade it became
      clear that the presence of these antibodies was highly predictive of and specific
      for RA, and illustrating the importance of ACPA. Therefore, the presence of these
      antibodies is one of the new American College of Rheumatology (ACR)/European
      League Against Rheumatism (EULAR) 2010 criteria for RA. Apart from the presence
      of these antibodies, the composition of this antibody response matures during RA
      development. This review summarizes the current knowledge of the characteristics
      of ACPA in RA development.

PMID- 21732052
TI  - Measuring radiologist workload: how to do it, and why it matters.
AB  - This article discusses the results and implications of a nationwide survey of
      radiologist workload. Although the results are specific to one country, the
      method used, the underlying issues and the discussion engendered should be of
      interest to all radiologists worldwide. The balance between quality and quantity
      is highlighted, and the growing impact of activities outside of traditional
      reporting is considered. Variations in health care funding and staffing amongst
      countries clearly influence patterns of workload. It is hoped that this
      discussion will lead other radiologists to consider the method used, and to
      analyse workload in other countries, with a view to creating more robust workload
      data and stimulating debate.

PMID- 21732053
TI  - Ambulatory blood pressure monitoring: from old concepts to novel insights.
AB  - Ambulatory blood pressure monitoring (ABPM) is an out-of-office technique for the
      assessment of 24-h blood pressure measurements. ABPM is indicated to diagnose
      many conditions, including white-coat hypertension, resistant hypertension,
      episodic hypertension, nocturnal hypertension, autonomic dysfunction, hypotension
      secondary to excessive usage of antihypertensive medication, and masked
      hypertension. ABPM gives a better prediction of clinical outcomes in patients
      with hypertension and cardiovascular diseases when compared to office blood
      pressure measurements. Recently, several new indices have been introduced with
      the aim of predicting various clinical end-points in several patient populations.
      In this review, we aimed to determine the clinical utility of 24-h ABPM and its
      potential implications for the management of hypertension in patients with a high
      risk of cardiovascular mortality and morbidity, as well as various novel indices
      that can predict clinical end-points in different patient populations.

PMID- 21732054
TI  - 1H, 13C and 15N backbone and side-chain resonance assignments of Drosophila
      melanogaster Ssu72.
AB  - Ssu72 helps regulate transcription and co-transcriptional mRNA processing by
      dephosphorylating serine residues at the 5th position in the heptad repeats of
      the C-terminal domain of RNA polymerase II. Here we use multidimensional,
      multinuclear NMR experiments to assign the backbone and side-chain resonances of
      the 23 kDa Ssu72 from Drosophila melanogaster in the phosphate-bound state, and
      use NMR titrations to examine the phosphate-binding properties of three active
      site mutants.

PMID- 21732055
TI  - Backbone and side chain NMR resonance assignments for an archaeal homolog of the
      endonuclease Nob1 involved in ribosome biogenesis.
AB  - Eukaryotic ribosome biogenesis requires the concerted action of ~200 auxiliary
      protein factors on the nascent ribosome. For many of these factors structural and
      functional information is still lacking. The endonuclease Nob1 has been recently
      identified in yeast as the enzyme responsible for the final cytoplasmatic
      trimming step of the pre-18S rRNA during the biogenesis of the small ribosomal
      subunit. Here we report the NMR resonance assignments for a Nob1 homolog from the
      thermophilic archeon Pyrococcus horikoshii as a prerequisite for further
      structural studies of this class of proteins.

PMID- 21732056
TI  - Analysis of failed surgery for patellar instability in children with open growth
      plates.
AB  - PURPOSE: Many surgical procedures have been proposed to treat recurrent patellar
      dislocation in children. In recent years, a more tailored approach considering
      the underlying pathology has been advocated. The aim of the study was to analyze
      a group of patients with recurrent patellofemoral instability after unsuccessful
      operative stabilization (Roux-Goldthwait procedure, lateral release, medial
      reefing or in combination) in childhood and adolescence. METHODS: A total of 37
      children and adolescents with recurrent patellofemoral instability despite
      previous surgery were analyzed retrospectively. Radiographic examination included
      AP and lateral views to assess patella alta and limb alignment. MRI was performed
      to evaluate trochlear dysplasia and tibial tubercle-trochlear groove (TTTG)
      distance. As a control group, 23 age- and sex-matched adolescents that were
      treated with a favorable outcome after medial reefing alone or combined with a
      Roux-Goldthwait procedure were analyzed. RESULTS: Severe trochlear dysplasia
      (type B-D according to Dejour) as detected on MRI scans was found significantly
      more often in the study group (89%) than in the control group (21%). No
      statistical difference of patellar height ratio (Insall-Salvati index) and TTTG
      distance between the two groups could be found. CONCLUSION: Of the measured
      parameters, only the incidence of trochlear dysplasia was increased. Trochlear
      dysplasia therefore seems to be a major risk factor for failure of operative
      stabilization of recurrent patellofemoral instability in children and
      adolescents. The results in children are in consensus with the literature in
      adults that a more tailored operative therapy including reconstruction of the
      MPFL and trochleaplasty has to be considered. LEVEL OF EVIDENCE: Retrospective
      study, Level III.

PMID- 21732057
TI  - Does computer-assisted surgery improve postoperative leg alignment and implant
      positioning following total knee arthroplasty? A meta-analysis of randomized
      controlled trials?
AB  - PURPOSE: Computer-assisted surgery has been proposed as a technique to improve
      implant alignment during total knee arthroplasty (TKA). However, there is still a
      debate over the accuracy of placing the femoral and tibial components using
      computer-assisted systems in TKA. The aim of this study is to establish whether
      computer-assisted surgery leads to superior mechanical leg axis and implant
      positioning than conventional technique in patients with primary TKA. METHODS:
      Major electronic databases were systematically searched to identify relevant
      studies without language restriction. A meta-analysis of 41 randomized controlled
      trials (RCTs) or quasi-RCTs was performed in a random effects model. A subgroup
      analysis was conducted by type of navigation system to explore the clinical
      heterogeneity between these trials. The following radiographic parameters were
      used to compare computer-assisted surgery with conventional technique: (1)
      mechanical leg axis, (2) femoral component coronal alignment, (3) tibial
      component coronal alignment, (4) femoral component sagittal alignment, and (5)
      tibial component sagittal alignment. RESULTS: For the mechanical leg axis and
      coronal positioning of femoral and tibial components, there are statistically
      significant reductions in the number of patients with malalignment in the CAS
      group if the outlier cutoff value is +/-3 or 2 degrees  in the coronal and
      sagittal planes, respectively. Subgroup analysis demonstrates that CT-free
      navigation systems provide better alignment than conventional techniques in the
      coronal and sagittal alignment of femoral components within +/-3 and 2 degrees .
      If the outlier cutoff value for the tibial sagittal alignment is +/-2 degrees ,
      the outlier percentages are higher in the CT-free navigation group than in the
      conventional group. However, there was no significant difference in the tibial
      sagittal alignment at +/-3 degrees . CONCLUSION: Computer-assisted surgery does
      improve mechanical leg axis and component orientation in TKAs. However, high
      quality RCTs are necessary to determine whether surgeons could use computer
      assisted techniques to achieve a targeted tibial slope in TKA. LEVEL OF EVIDENCE:
      Therapeutic study (Systematic review of Level I/II studies), Level II.

PMID- 21732058
TI  - Isolation, identification and sequence analysis of a thioredoxin h gene, a member
      of subgroup III of h-type Trxs from grape (Vitis vinifera L. cv. Askari).
AB  - Thioredoxins (Trxs) are small ubiquitous proteins which play a regulatory role in
      a variety of cellular processes. In contrast to other organisms, plants have a
      great number of Trx types, consisting of six well-defined groups: f, m, x, and y
      in chloroplasts, o in mitochondria, and h mainly in cytosol. A full-length cDNA,
      designated VvCxxS2, encoding Trx h polypeptide was isolated and cloned from grape
      (Vitis vinifera L. cv. Askari) berries organ by reverse transcription polymerase
      chain reaction (RT-PCR). The cDNA was 381 bp nucleotides in length with a deduced
      amino acid of 126 residues, possessing a WCIPS active site, which belongs to the
      subgroup III of h-type Trxs based on phylogenetic analysis. The calculated
      molecular mass and the predicted isoelectric point of the deduced polypeptide are
      14.25 kDa and 4.68, respectively. Nucleotide sequence analysis of genomic DNA
      fragment of VvCxxS2 gene revealed that this gene possesses two introns at
      positions identical to the previously sequenced Trx h genes. A modeling analysis
      indicated that VvCxxS2 shares a common structure with other Trxs, and is
      preferably reduced by Grx rather than NADPH-dependent thioredoxin reductase
      (NTR). The deduced protein sequence showed a high similarity to Trx h from other
      plants, in particular from castor bean (Ricinus communis), Betula pendula and
      sweet orange (Citrus sinensis). Semiquantitative RT-PCR experiments indicated
      that the transcripts of VvCxxS2 gene are present in all plant organs and
      different developmental stages. In addition, the higher expression of the VvCxxS2
      gene was observed in berry organ as compared to the other organs.

PMID- 21732059
TI  - Suppression of lung cancer metastasis-related protein 1 (LCMR1) inhibits the
      growth of colorectal cancer cells.
AB  - Lung cancer metastasis-related protein 1 (LCMR1) is a critical subunit of the
      mediator complex, and plays an important role in the elaborate regulation of gene
      transcription. However, the functional role of LCMR1 in colorectal carcinoma
      (CRC) has not been clarified. In this study, LCMR1 expression in CRC specimens
      was quantified by using the quantitative reverse transcription polymerase chain
      reaction method. The effect of downregulation of LCMR1 by lentivirus-mediated
      small hairpin RNA (shRNA) on CRC cell proliferation and tumorigenesis was
      explored. There was a higher expression of LCMR1 in CRC tissue in comparison with
      adjacent normal colon tissue (P < 0.05). LCMR1 gene was effectively knocked down
      in human CRC RKO and DLD-1 cells that infected with lentivirus delivering shRNA
      against LCMR1, which resulted in inhibition of cell proliferation and
      augmentation of G0/G1 phase proportion. Moreover, the tumorigenicity of RKO cells
      was also dramatically inhibited after LCMR1 was knocked down. In conclusion, our
      results suggest that LCMR1 promotes CRC cell growth, and lentivirus-mediated
      silencing of LCMR1 may contribute to the gene therapy for CRC.

PMID- 21732060
TI  - Estrogen related receptor alpha-induced adipogenesis is PGC-1beta-dependent.
AB  - Previous report showed that Estrogen related receptor alpha (ERRalpha) knockout
      mice had a significant reduction in adipose tissue deposition. Although it was
      reported that ERRalpha could promote adipogenesis in several immortalized
      preadipocytes cell lines, the mechanism behind which is still unclear to date.
      Besides, the expression pattern of ERRalpha in white adipose tissue is rarely
      examined. Here, we show that the expression of ERRalpha in primary cultured
      adipocytes is closely associated with adipogenesis. Besides, we found that
      peroxisome proliferator-activated receptor-gamma coactivator 1beta (PGC-1beta)
      play an important role in regulating ERRalpha-induced adipogenesis. ERRalpha
      induced adipogenesis was greatly attenuated when knocking down PGC-1beta
      expression, while rescued by overexpression of PGC-1beta. However, PGC-1beta
      could still promote adipogenesis when suppressing ERRalpha expression.
      Furthermore, we demonstrated that ERRalpha could transcriptionally active PGC
      1beta expression and then enhance the formation of sterol-regulatory-element
      binding protein-1c (SREBP-1c)/PGC-1beta complex and peroxisome proliferator
      activated receptor-gamma (PPARgamma)/PGC-1beta complex. Taken together, these
      results indicate that ERRalpha-induced adipogenesis is triggered by modulating
      the expression of PGC-1beta.

PMID- 21732061
TI  - Unilateral fixed mydriasis: an uncommon presentation of temporal lobe epilepsy.

PMID- 21732062
TI  - Central pontine myelinolysis associated with pancreatic diabetes.

PMID- 21732063
TI  - Bilateral ocular perineuritis as the presenting feature of acute syphilis
      infection.

PMID- 21732064
TI  - Meningitis associated with bilateral optic papillitis following Mycoplasma
      pneumoniae infection.
AB  - Mycoplasma pneumoniae (M. pneumoniae) is a frequent cause for human infection,
      and central nervous system disease associated with M. pneumoniae infection is
      being reported with increasing frequency. We described herein a 60-year-old woman
      who developed meningitis associated with bilateral optic papillitis following M.
      pneumoniae infection and discussed the possible mechanisms. To our knowledge,
      there have been only a few reports that described the meningitis complicated by
      bilateral optic papillitis in association with M. pneumoniae infection. Our case
      highlighted the protean neurological manifestations of M. pneumoniae infection.

PMID- 21732065
TI  - Fetal variant of circle of the Willis and bilateral symmetrical parietal stroke.
AB  - We described a rare case in which a congenital abnormal vascular structure
      associated with mild hyperhomocysteinemia could have caused an ischemic stroke,
      with an unusual localization in the border-zone of MCA and PCA. We think that the
      lack of compensatory flow distribution from the right vertebral artery and the
      right posterior communicating artery probably determined the bilateral ischemic
      lesions in a patient, who possibly had hypotensive crisis.

PMID- 21732066
TI  - Cardiovascular safety of aripiprazole and pimozide in young patients with
      Tourette syndrome.
AB  - The pharmacotherapy for tic management in Tourette syndrome (TS) relies on
      neuroleptics, which have been associated with electrocardiographic abnormalities,
      including QTc interval prolongation. This study assessed the cardiovascular
      safety of the newer antipsychotic aripiprazole in comparison with the neuroleptic
      pimozide among young patients affected by TS. Fifty patients aged 6-18 years were
      assigned to either pimozide (n = 25; mean daily dose 4.4 mg/die) or aripiprazole
      (n = 25; 5.3 mg/die) treatment for up to 24 months. All patients underwent five
      serial cardiovascular assessments (baseline, 6, 12, 18 and 24 months). The group
      treated with pimozide showed significant changes in blood pressure (decreased),
      QT and QTc (both prolonged). The aripiprazole group showed changes from baseline
      to peak values in blood pressure (increased), whilst modifications in QT and QTc
      were not statistically significant. At equivalent doses, aripiprazole is
      characterised by a safer cardiovascular profile than pimozide, being associated
      with a lower frequency of QTc prolongation.

PMID- 21732067
TI  - Coagulation profile, haematological and biochemical changes in kids naturally
      infected with peste des petits ruminants.
AB  - The aim of this study was to examine the coagulation profile in peste des petits
      ruminant (PPR) in kids. Five kids from a group of 150 animals (72 goats and 78
      kids) were brought to the Veterinary Medical Teaching Hospital from a farm in
      Burdur province (Turkey) with nasal and ocular discharges and diarrhea. Fifteen
      goats and 41 kids had died due to diarrhea and three kids were presented to the
      Department of Pathology for diagnosis. Blood samples were taken from 12 ill
      animals (infected group) for haematological and biochemical analysis. In
      addition, five healthy kids were examined from another healthy flock (control
      group). Leukocyte and lymphocyte numbers of infected group showed significant
      declinations in comparison to control group (<=0.001). Haemorrhages in all organs
      of digestive system and small haemorrhagic areas in liver were caused to decrease
      in erythrocyte and haematocrit values (p <= 0.001) in infected group.
      Concentrations of blood urea nitrogen (BUN) (p <= 0.01) and creatinine (p <=
      0.001) in infected group were significantly higher than control group. Compared
      to control group, significant increases were determined in serum concentrations
      of alkaline phosphatase (ALP) (p <= 0.01), aspartate aminotransferase (AST) (p <=
      0.001) and alanine aminotransferase (ALT) (p <= 0.001) in the infected group. No
      significant differences were observed between the infected and control groups for
      serum gamma glutamyl-transferase (GGT) concentration value. In our study,
      thrombocytopenia (p <= 0.001) together with prolonged activated partial
      thromboplastin time (APTT; p <= 0.01) and prothrombin time (PT; p <= 0.001) may
      show that disseminated intravascular coagulopathy which can occur in kids with
      PPR.

PMID- 21732068
TI  - Fatty acid profile of hair lambs and their crossbreds slaughtered at different
      weights.
AB  - This study aims to investigate the effect of breed and slaughter weight on fatty
      the acid profile of the Longissimus dorsi muscle in lambs. Twenty-four Santa Ines
      (SI), 24.5 Ile de France * 0.5 Santa Ines (Ile * SI) and 12.5 Texel * 0.5 Santa
      Ines (Te * SI), slaughtered at different weights (30, 35, 40, and 45 kg), were
      evaluated. The animals were reared with creep feeding to weaning and were feedlot
      finished, receiving a diet composed of 30% hay and 70% concentrate. The analyses
      of fatty acids were carried out on the Longissimus muscle of the 13th rib. The
      experiment was in a three by four factorial design. The total mean saturated
      fatty acid level was 44.88%, with 43.30% monounsaturated fats and 1.72%
      polyunsaturated. The major fatty acids found included oleic (43%), palmitic
      (22%), and stearic (18%). The concentration of desirable fatty acids varied from
      61.56% to 66.78%, with Te * SI (66.78%) having the highest levels (P < 0.05). The
      slaughter weight affected (P < 0.05) the saturated and unsaturated (both mono and
      poly) fatty acid profiles. The 35-kg slaughter weight showed the most desirable
      fatty acid profile. The saturated myristic and stearic fatty acids decreased with
      an increase in the slaughter weight, but oleic acid increased. In the conditions
      of the present study, the meat from Santa Ines and Texel * Santa Ines lambs had
      fatty acid profiles more beneficial for human health due to the higher levels of
      unsaturated fatty acids.

PMID- 21732069
TI  - Brassinolide alleviates salt stress and increases antioxidant activity of cowpea
      plants (Vigna sinensis).
AB  - Soil salinity is one of the most severe factors limiting growth and physiological
      response in Vigna sinensis plants. Plant salt stress tolerance requires the
      activation of complex metabolic activities including antioxidative pathways,
      especially reactive oxygen species and scavenging systems within the cells which
      can contribute to continued growth under water stress. The present investigation
      was carried out to study the role of brassinolide in enhancing tolerance of
      cowpea plants to salt stress (NaCl). Treatment with 0.05 ppm brassinolide as
      foliar spray mitigated salt stress by inducing enzyme activities responsible for
      antioxidation, e.g., superoxide dismutase, peroxidase, polyphenol oxidase, and
      detoxification as well as by elevating contents of ascorbic acid, tocopherol, and
      glutathione. On the other hand, total soluble proteins decreased with increasing
      NaCl concentrations in comparison with control plants. However, lipid
      peroxidation increased with increasing concentrations of NaCl. In addition to,
      the high concentrations of NaCl (100 and 150 mM) decreased total phenol of cowpea
      plants as being compared with control plants. SDS-PAGE of protein revealed that
      NaCl treatments alone or in combination with 0.05 ppm brassinolide were
      associated with the disappearance of some bands or appearance of unique ones in
      cowpea plants. Electrophoretic studies of alpha-esterase, beta-esterase,
      polyphenol oxidase, peroxidase, acid phosphatase, and superoxide dismutase
      isoenzymes showed wide variations in their intensities and densities among all
      treatments.

PMID- 21732070
TI  - Progression of the lung cancer primary correlates with the identification of new
      brain metastases after initial radiosurgery.
AB  - We retrospectively evaluated the relationship between the response of lung
      lesions and distant progression-free survival (DPFS) after radiosurgery in
      patients with brain metastases. A total of 47 consecutive patients were treated
      with radiosurgery for brain metastases. Distant progression was defined as a new
      enhancing intracranial tumor or leptomeningeal enhancement noted on follow-up
      magnetic resonance imaging. Progression of lung lesions was defined as follows:
      (1) a 20% increase in the summed diameter of the target lesions; (2) an absolute
      increase of 5 mm when the summed diameter was very small; or (3) detection of new
      lesions in the lung. Distant progression after radiosurgery was observed for
      twenty-one (44.7%) patients; we observed development of new distant metastases in
      nine patients, development of leptomeningeal seeding in eight patients, and
      combined failure of distant progression and local control failure in four
      patients. Forty-two (89.4%) patients had lung lesions at the time of
      radiosurgery, and progression of their lung lesions during the post-radiosurgery
      follow-up period was observed for 18 (38.3%) of these. The median DPFS was 7.00
      months (95% CI, 6.153-7.847). Actuarial DPFS 3, 6, and 12 months after
      radiosurgery was 81.5, 61.3, and 36.7%, respectively. In multivariate analysis,
      only the criterion progression of lung lesions reached statistical and
      independent significance (P = 0.021, OR = 3.372, 95% CI, 1.200-9.480). The
      response of lung lesions after radiosurgery is likely to be a good predictor of
      DPFS after radiosurgery in patients with brain metastases.

PMID- 21732071
TI  - The genotoxic effect of radiofrequency waves on mouse brain.
AB  - Concerns about the health effects of radiofrequency (RF) waves have been raised
      because of the gradual increase in usage of cell phones, and there are scientific
      questions and debates about the safety of those instruments in daily life. The
      aim of this study is to evaluate the genotoxic effects of RF waves in an
      experimental brain cell culture model. Brain cell cultures of the mice were
      exposed to 10.715 GHz with specific absorbtion rate (SAR) 0.725 W/kG signals for
      6 h in 3 days at 25 degrees C to check for the changes in the micronucleus (MNi)
      assay and in the expression of 11 proapoptotic and antiapoptotic genes. It was
      found that MNi rate increased 11-fold and STAT3 expression decreased 7-fold in
      the cell cultures which were exposed to RF. Cell phones which spread RF may
      damage DNA and change gene expression in brain cells.

PMID- 21732072
TI  - Gangliocytoma of the medulla oblongata demonstrating high tracer uptake on
      positron emission tomography.

PMID- 21732073
TI  - Gamma knife radiosurgery for cranial neurocytomas.
AB  - Gamma-knife surgery may be an effective alternative for treatment of central
      neurocytomas owing to its relative safety compared with conventional
      radiotherapy. In this paper we present results of gamma-knife treatment (GKS) of
      residual or recurrent neurocytomas. Twenty-two patients (14 female, 8 male) with
      recurrent or residual neurocytomas who underwent GKS were included. Diagnosis was
      based on histological findings. The proliferative potential of the tumors was
      examined by immunostaining with MIB-1 antibody, which is specific for detection
      of Ki-67 antigen. Tumor volume was determined by using post-gadolinium magnetic
      resonance images. After GKS treatment, MR imaging was scheduled at three-month
      intervals in the first year, at six months intervals in the second year, and
      yearly thereafter. Histopathological diagnoses were: 18 cases of central
      neurocytomas, two liponeurocytomas, one cerebral neurocytoma and one cerebellar
      neurocytoma. The MIB1 labeling index (LI) varied from 0 to 5.7%. Marked reduction
      in tumor volume was seen in 15 patients. In six patients, the tumor volume
      remained unchanged, and progression was observed for one patient. No
      complications because of GKS were noted. Shrinking effect on tumor volume
      increased with increasing duration of follow-up. On the other hand, high MIB
      labeling index did not seem to have an effect on tumor response to GKS treatment.
      Findings of this study suggest that GKS is an effective and safe treatment
      alternative for residual or recurrent neurocytomas. However, its effectiveness
      should be confirmed with larger studies.

PMID- 21732074
TI  - Ultra-sensitive quantification of sub-nanomolar levels of iodine in blood serum
      samples by kinetic-spectrophotometric method.
AB  - A simple and sensitive kinetic-spectrophotometric method is developed for the
      determination of trace amounts of iodine in blood serum samples based on its
      catalytic effect on the oxidation of Nile Blue A by potassium bromate in sulfuric
      acid medium and at 25 degrees C. The absorbance is measured at 595.5 nm with the
      fixed-time method. The optimization of the operating conditions regarding
      concentration of the reagents, temperature, and interferences are also
      investigated. The calibration curve is linear over the concentration range
      between 20.0 to 500.0 ng ml(-1) of iodine with good precision and accuracy. The
      detection limit of the method is down to 12.0 ng ml(-1). The relative standard
      deviation for a standard solution of 100.0 ng ml(-1) of iodine is 1.32% (n = 10).
      The proposed method provides a highly sensitive, selective, and relatively rapid
      assay for iodine at ultra trace level without any pre-concentration and
      separation step. The method was applied to the determination of iodine in blood
      serum samples. The analytical results of the real samples were in excellent
      agreement with standard method.

PMID- 21732075
TI  - CD44-positive cells are candidates for astrocyte precursor cells in developing
      mouse cerebellum.
AB  - Neural stem cells are generally considered to be committed to becoming precursor
      cells before terminally differentiating into either neurons or glial cells during
      neural development. Neuronal and oligodendrocyte precursor cells have been
      identified in several areas in the murine central nervous system. The presence of
      astrocyte precursor cells (APCs) is not so well understood. The present study
      provides several lines of evidence that CD44-positive cells are APCs in the early
      postnatal mouse cerebellum. In developing mouse cerebellum, CD44-positive cells,
      mostly located in the white matter, were positive for the markers of the
      astrocyte lineage, but negative for the markers of mature astrocytes. CD44
      positive cells were purified from postnatal cerebellum by fluorescence-activated
      cell sorting and characterized in vitro. In the absence of any signaling
      molecule, many cells died by apoptosis. The surviving cells gradually expressed
      glial fibrillary acidic protein, a marker for mature astrocytes, indicating that
      differentiation into mature astrocytes is the default program for these cells.
      The cells produced no neurospheres nor neurons nor oligodendrocytes under any
      condition examined, indicating these cells are not neural stem cells. Leukemia
      inhibitory factor greatly promoted astrocytic differentiation of CD44-positive
      cells, whereas bone morphogenetic protein 4 (BMP4) did not. Fibroblast growth
      factor-2 was a potent mitogen for these cells, but was insufficient for survival.
      BMP4 inhibited activation of caspase-3 and greatly promoted survival, suggesting
      a novel role for BMP4 in the control of development of astrocytes in cerebellum.
      We isolated and characterized only CD44 strongly positive large cells and
      discarded small and/or CD44 weakly positive cells in this study. Further studies
      are necessary to characterize these cells to help determine whether CD44 is a
      selective and specific marker for APCs in the developing mouse cerebellum. In
      conclusion, we succeeded in preparing APC candidates from developing mouse
      cerebellum, characterized them in vitro, and found that BMPs are survival factors
      for these cells.

PMID- 21732077
TI  - Differential expression of the transcripts of Spartina alterniflora Loisel
      (smooth cordgrass) induced in response to petroleum hydrocarbon.
AB  - Petroleum hydrocarbons (PHC) in soil are potentially toxic to plants and exert
      negative effect on the environment and human health. To understand the effect of
      PHC on the gene expression profile of a wetland plant Spartina alterniflora in
      the coastal Louisiana, plants were subject up to 40% PHC under greenhouse
      conditions. The plants exposed to PHC showed 21% reduction of leaf total
      chlorophyll after 2 weeks of stress. Using 20 annealing control primers, 28
      differentially expressing genes (DEGs) were identified in leaf and root tissues
      of S. alterniflora in response to PHC stress. Eleven of these 28 DEGs had role in
      either molecular function (chlorophyll a-b binding protein, HSP70, NADH, RAN1
      binding protein, and RNA-binding protein), biological processes (cell wall
      protein, nucelosome/chromatin assembly factor) or cellular function (30 S
      ribosomal protein). This indicated that genes in different regulatory pathways of
      S. alterniflora were involved in response to PHC. All DEGs showed reduced
      transcript accumulation in root under oil stress, whereas they showed up- or down
      regulation in their transcript abundance in leaf depending on the concentration
      of the PHC. The genes identified through this study could be used in the genetic
      screen of S. alterniflora for resistance to PHC.

PMID- 21732076
TI  - IL-1beta down-regulates ADAMTS-13 mRNA expression in cells of the central nervous
      system.
AB  - ADAMTS-13 is the Von Willebrand factor (vWF) cleaving protease, responsible for
      the cleavage and down-regulation of the pro-thrombotic properties of ultra large
      VWF multimers. It is expressed predominantly by the hepatic stellate cells of the
      liver, but is also found to be expressed in other tissues, including brain.
      Reduced ADAMTS-13 is associated with a variety of thrombotic microangiopathies.
      Since the cellular origin and regulation of ADAMTS-13 expression in the brain is
      unknown, we aimed to investigate this in four different central nervous system
      (CNS)-derived cell lines, SHSY-5Y (human neuroblastoma), U373 (human
      astroglioma), CHME-3 (human foetal microglia) and hCMEC/D3 (adult human brain
      endothelial cells). All cell lines expressed ADAMTS-13 mRNA constitutively with
      neuroblastoma cells showing the highest expression. Interleukin (IL)-1beta down
      regulated ADAMTS-13 mRNA expression in astroglioma cells and microglial cells
      whereas TNF and IL-6 treatment showed no significant differences in ADAMTS-13
      mRNA expression in any cell line tested. ADAMTS-13 protein expression was reduced
      in a dose-dependent manner only in astroglioma cells following stimulation by IL
      1beta. The ability of IL-1beta to significantly reduce ADAMTS-13 mRNA expression
      in human microglia and astroglioma cells suggests a role in the haemostasis of
      the local microenvironment under inflammatory conditions. This is the first
      report of ADAMTS-13 expression in cells of the CNS; however, its function remains
      to be determined.

PMID- 21732078
TI  - Massive intra-abdominal haemorrhage following stapled haemorrhoidopexy.

PMID- 21732079
TI  - [Heterotopic gastric mucosa of the rectum. Case report with literature review].
AB  - Heterotopic gastric mucosa is a rare finding in the rectum. Apart from two other
      hypotheses, a misdifferentiation of entodermal stem cells is the most widely
      accepted aetiopathogenetic assumption today. Due to acid secretion, the lesions
      predominantly manifest with hematochezia. Therapeutic options include medicinal
      therapy and particularly (endoscopic) removal. From the pathologist's point of
      view a careful evaluation is required also in terms of basically possible
      dysplastic or malignant changes.

PMID- 21732080
TI  - [Rabies transmission through organ transplantation].
AB  - Classic rabies is a progressive and lethal infectious disease of animals, which
      may be transmitted to humans. Inter-human infections are extremely rare. The
      present case describes transmittal of rabies virus by lung transplantation from
      an infected donor. Histologically, a lymphocytic encephalomyelitis with neuronal
      cytoplasmic inclusion bodies was found. Immunohistochemically, rabies virus
      antigen was detected in the central, autonomous and peripheral nervous system. By
      means of electron microscopy, virions were demonstrated in the brain. A central
      task of health care in transplantations is the detection of uncommon infectious
      agents and the prevention of their transmittal.

PMID- 21732083
TI  - Deletion of Ia-2 and/or Ia-2beta in mice decreases insulin secretion by reducing
      the number of dense core vesicles.
AB  - AIMS/HYPOTHESIS: Islet antigen 2 (IA-2) and IA-2beta are dense core vesicle (DCV)
      transmembrane proteins and major autoantigens in type 1 diabetes. The present
      experiments were initiated to test the hypothesis that the knockout of the genes
      encoding these proteins impairs the secretion of insulin by reducing the number
      of DCV. METHODS: Insulin secretion, content and DCV number were evaluated in
      islets from single knockout (Ia-2 [also known as Ptprn] KO, Ia-2beta [also known
      as Ptprn2] KO) and double knockout (DKO) mice by a variety of techniques
      including electron and two-photon microscopy, membrane capacitance, Ca(2+)
      currents, DCV half-life, lysosome number and size and autophagy. RESULTS: Islets
      from single and DKO mice all showed a significant decrease in insulin content,
      insulin secretion and the number and half-life of DCV (p < 0.05 to 0.001).
      Exocytosis as evaluated by two-photon microscopy, membrane capacitance and Ca(2+)
      currents supports these findings. Electron microscopy of islets from KO mice
      revealed a marked increase (p < 0.05 to 0.001) in the number and size of
      lysosomes and enzymatic studies showed an increase in cathepsin D activity (p <
      0.01). LC3 protein, an indicator of autophagy, also was increased in islets of KO
      compared with wild-type mice (p < 0.05 to 0.01) suggesting that autophagy might
      be involved in the deletion of DCV. CONCLUSIONS/INTERPRETATION: We conclude that
      the decrease in insulin content and secretion, resulting from the deletion of Ia
      2 and/or Ia-2beta, is due to a decrease in the number of DCV.

PMID- 21732084
TI  - Fenestrations of the intracranial vertebrobasilar system diagnosed by MR
      angiography.
AB  - INTRODUCTION: Fenestrations of cerebral arteries are most common in the
      vertebrobasilar (VB) system, and magnetic resonance (MR) angiographic studies of
      these variations are sparse. METHODS: We retrospectively reviewed MR angiographic
      images of 3,327 patients; images were obtained using two 1.5-T imagers and picked
      up fenestrations of the intracranial vertebral artery (VA), VB junction, and
      basilar artery (BA) for evaluation. RESULTS: In 92 patients, we found 93
      fenestrations (2.80%), which included 18 of the intracranial VA (0.54%
      prevalence), 6 of the VB junction (0.18%), and 69 of the BA (2.07%). Most VA
      fenestrations were large, and the posterior inferior cerebellar artery arose from
      the fenestrated segment in 10 patients (56%). Fenestrations of the VB junction
      were small and triangular. Sixty-five (94%) of the 69 BA fenestrations were
      located at the proximal segment and had small slit-like configurations. The
      anterior inferior cerebellar artery arose from the fenestrated segment in 27
      patients (37%). We found 18 cerebral aneurysms in 16 (17%) of the 92 patients
      with fenestration but detected only one aneurysm at the fenestration. CONCLUSION:
      The overall prevalence of fenestrations of the intracranial VB system was 2.77%.
      We found associated cerebral aneurysms relatively frequently but rarely at the
      fenestration.

PMID- 21732085
TI  - Angiographically confirmed stent over expansion in the internal carotid artery
      during stenting: incidence, predictors, and outcomes.
AB  - INTRODUCTION: Selection of the appropriate diameter of stent is difficult in
      patients with the size mismatch between the internal carotid artery (ICA) and the
      common carotid artery (CCA). Although stent overexpansion (SOE) in the ICA after
      carotid artery stenting (CAS) is suspected of producing restenosis, SOE has not
      been well established. We discuss its incidence, predictors, and outcomes.
      METHODS: We retrospectively reviewed follow-up angiographs of 206 CAS-treated
      arteries in 201 patients who had undergone CAS. SOE was defined as angiographic
      evidence of an intimal gap between the non-stented normal and the dilated stented
      ICA at the distal stent edge. We also collected data on the patients' clinical
      status, comorbidities, and radiological and procedural data. Patients with SOE
      were further followed up closely by duplex ultrasound scans. RESULTS: SOE was
      detected in nine of 206 CAS-treated ICAs (4.4%). Univariate analysis revealed a
      significant association between SOE and open-cell stents, the stent diameter (p <
      0.01), pre-procedural stenosis, the ICA diameter, ICA/CCA ratio, and the
      ICA/stent ratio (p < 0.05). Entering these variables into a logistic regression
      model, open-cell stents were the only variable that significantly increased the
      risk for SOE (OR 2.36; 95% CI 0.99-4.60; p < 0.05). During a mean clinical follow
      up of 31.1 months (range 24-39 months), none of the patients with SOE developed
      new neurologic ischemic symptoms, stent-edge stenosis, or in-stent restenosis.
      CONCLUSION: SOE after CAS was not associated with clinical adverse effects. This
      study suggests that the diameter of stent should be determined by reference to
      the CCA diameter without respect to the ICA diameter.

PMID- 21732086
TI  - Functional analysis and gene expression profile of umbilical cord blood
      regulatory T cells.
AB  - The aim of the study was to analyze and compare the functional properties and the
      gene expression profile of regulatory T cells (Tregs) isolated from cord blood
      (CB) units (n = 23) and from the peripheral blood (PB) of adult normal donors (n
      = 13). Tregs were purified from mononuclear cells and expanded for 6 days with
      anti-CD3, anti-CD28, and IL-2. CB and PB Tregs presented similar immunophenotypic
      features. However, Tregs isolated from CB presented a much higher expansion
      capacity; this was confirmed by the genomic characterization that showed in CB
      derived Tregs significant enrichments of genes involved in cell proliferation,
      chromatin modification, and regulation of gene expression. All samples were
      positive for the FoxP3 gene and protein after expansion. CB and PB expanded Tregs
      exerted a comparable and potent suppressive function on the proliferative
      reaction of autologous T cells stimulated by allogeneic dendritic cells and
      presented a high in vitro IL-10 production capacity. Gene profile analysis also
      revealed for PB Tregs significant enrichments of genes involved in the adaptive
      immune response. These data offer further insights into the understanding of the
      biology of CB transplantation indicating a possible role played by CB Tregs in
      the suppression of the allogeneic T cell response.

PMID- 21732087
TI  - Liver failure as the only clinical manifestation of multiple myeloma.

PMID- 21732088
TI  - The effects of compression on the image quality of digital panoramic radiographs.
AB  - Size reduction through compression is an important issue that needs to be
      investigated for possible effects on image quality. The aim of the present study
      was to evaluate the subjective image quality of digital panoramic radiographs
      which were lossless and lossy compressed for the visualization of various
      anatomical structures. Fifty-five digital panoramic radiographs in Tagged Image
      File Format (Tiff) were used in the study. Two types of lossy (Joint Photographic
      Experts Group (Jpeg)) and one type of lossless (Lempel-Ziv-Welch) compression
      were applied to the original radiographs. These radiographs were evaluated by two
      observers separately for the visibility of some anatomical structures with visual
      grading. Mean quality number for each radiograph was obtained. The differences
      between the mean quality numbers in each compression and original image mode were
      evaluated with Friedman test. Pair-wise comparisons revealed that there were
      statistically significant differences between all groups (p = 0.000) for all
      comparisons except for Jpeg_1 and Jpeg_2 groups. Kappa statistics was used to
      evaluate inter- and intra-observer agreements. Intra-observer agreements were
      ranging from 0.229 to 1.000 and inter-observer agreements were ranging from 0.154
      to 1.000. The observers had better inter- and intra-observer agreements in highly
      compressed Jpeg_1 images. The anatomical structures evaluated in this study had
      better visibility in Tiff images than Jpeg images except for mandibular canal and
      mental foramen. While Jpeg compressed images offer high inter- and intra-observer
      agreements, the visibility of anatomical structures are better in Tiff images
      except for mandibular canal and mental foramen.

PMID- 21732089
TI  - Tooth wear in the deciduous dentition of 5-7-year-old children: risk factors.
AB  - This study was conducted to investigate the distribution and severity of tooth
      wear in deciduous dentition and its relationship with possible risk factors. A
      stratified cluster sample of 243 5-7-year-old children was examined using the
      tooth wear index of Smith and Knight, and their exposure to intrinsic and
      extrinsic risk factors was retrospectively investigated through a structured
      questionnaire. The severity of wear was quantitatively estimated by the number of
      surfaces with affected dentine and by the cumulative score of the sextants, based
      on the Basic Erosive Wear Examination scoring system. Only 1.6% of the children
      were tooth wear free, whereas 45.6% had moderate to severe wear involving
      dentine. Maxillary canines were the most affected teeth (83.2%), and
      occlusal/incisal the most affected surfaces (52.7%). The likelihood of tooth wear
      involving dentine was greater in boys than girls (OR = 1.72), in immigrants than
      in Greeks (OR = 1.93), and in 6- and 7-year olds than in 5-year olds (OR = 2.78
      to 2.93). After adjustment for age, gender, and nationality, exposure to several
      dietary factors and especially to soft drinks was found to significantly affect
      the prevalence (OR = 1.27) and the severity of tooth wear. Every additional
      serving/week of consumption of soft drinks increases the number of surfaces with
      dentine affected by 0.03 per year (p < 0.05) and the cumulative score of sextants
      by 0.04 (p < 0.05). The cluster of children with the higher prevalence and
      severity of tooth wear had an average exposure to soft drinks of 10 servings/week
      for a duration of 4 years. The cumulative score of sextants was better predicted
      by the assessed risk factors, in comparison with the number of surfaces with
      affected dentine. Tooth wear is a common condition in children, related both to
      the physiological process of aging of dentition and to the erosive effect of
      dietary factors. Strategies to reduce the intake of soft drinks in children are
      expected to have multiple benefits preventing tooth wear in childhood and in
      later life, as well as many other general and oral health diseases.

PMID- 21732090
TI  - Short-term consumption of probiotic lactobacilli has no effect on acid production
      of supragingival plaque.
AB  - Acidogenicity and the levels of mutans streptococci (MS) in dental plaque after
      the use of Lactobacillus rhamnosus GG (LGG) and Lactobacillus reuteri were
      determined. The study had a randomised, double-blind, crossover design. Thirteen
      volunteers used tablets containing LGG or a combination of L. reuteri SD2112 and
      PTA 5289 for 2 weeks. At baseline and at the end of each tablet period, all
      available supragingival plaque was collected. Lactic acid production was
      determined from a fixed volume (8 MUl) of fresh plaque and the rest of the plaque
      was used for culturing MS and lactobacilli. The retention of probiotics to the
      plaque was assessed using PCR techniques. No probiotic-induced changes were found
      in the acidogenicity of plaque. Also, MS counts remained at the original level.
      The number of subjects with lactobacilli in plaque increased in the L. reuteri
      group (p = 0.011) but not in the LGG group. PCR analysis of plaque revealed the
      presence of LGG in four and L. reuteri in six subjects after the use of the
      probiotic. The use of the lactobacilli did not affect the acidogenicity or MS
      levels of plaque. Short-term consumption of LGG and L. reuteri appeared not to
      influence the acidogenicity of plaque.

PMID- 21732091
TI  - Molecular advances in reporter genes: the need to witness the function of stem
      cells in failing heart in vivo.
AB  - Stem cells possess the ability to terminally differentiate in cell phenotypes
      belonging to several different lineages. Over the last decade, transplant of
      adult stem cells into the injuried myocardium has been widely studied as a
      revolutionary approach to promote the non-pharmacological improvement or
      replacement of the lost function. In spite of the tantalizing perspectives and
      controversial results, several questions about the viability and biology of
      transplanted stem cells in the beating heart still remain unanswered, mostly
      because of the current technological limitations. Recent advances in bio- and
      nano-technology are allowing the development of molecular probes for imaging thus
      providing a better understanding of stem cells physiology and fate in vivo.
      Reporter gene based molecular imaging is a high-throughput and sensitive tool
      used to unscramble over time the mechanisms underlying cell-induced myocardial
      repair in vivo. To date, the employed reporter genes have been exogenous
      (proteins which are expressed after gene engineering), or endogenous (detected by
      tracer substrates). This review will highlight current and outstanding
      experimental investigations, which are developing new probes to monitor the fate
      of stem cells transplanted in failing myocardium in vivo.

PMID- 21732092
TI  - Proteomics profiling of human embryonic stem cells in the early differentiation
      stage.
AB  - The regulatory pathways responsible for maintaining human embryonic stem cells
      (hESCs) in an undifferentiated state have yet to be elucidated. Since these
      pathways are thought to be governed by complex protein cues, deciphering the
      changes that occur in the proteomes of the ESCs during differentiation is
      important for understanding the expansion and differentiation processes involved.
      In this study, we present the first quantitative comparison of the hESC protein
      profile in the undifferentiated and early differentiated states. We used iTRAQ
      (isobaric tags for relative and absolute quantification) labeling combined with
      two dimensional capillary chromatography coupled with tandem mass spectrometry
      (MULC-MS/MS) to achieve comparative proteomics of hESCs at the undifferentiated
      stage, and at 6, 48, and 72 h after initiation of differentiation. In addition,
      two dimensional electrophoresis (2-DE) was performed on differentiating hESCs at
      eleven points of time during the first 72 h of differentiation. The results
      indicate that during the first 48 h of hESC differentiation, many processes are
      initiated and are later reversed, including chromatin remodeling, heterochromatin
      spreading, a decrease in transcription and translation, a decrease in glycolytic
      proteins and cytoskeleton remodeling, and a decrease in focal and cell adhesion.
      Only 72 h after differentiation induction did the expression of the homeobox
      prox1 protein increase, indicating the beginning of developmental processes.

PMID- 21732093
TI  - Longitudinal observations of serum heparin cofactor II-thrombin complex in
      treated Mucopolysaccharidosis I and II patients.
AB  - Monitoring of therapeutic response in mucopolysaccharidosis (MPS) patients is
      problematic as most biomarkers are specific for either disease complications or
      specific organ system involvement. Recent studies have indicated that serum
      heparin-cofactor II-thrombin complex (HCII-T) may serve as an important biomarker
      in the group of MPSs where dermatan sulphate is stored. This complex forms when
      blood coagulates in the presence of glycosaminoglycans (GAGs) where the ultimate
      amount of HCII-T that forms reflects the concentration of circulating GAGs. We
      have studied serum HCII-T levels in 9 MPS I and 11 MPS II treated patients and
      have compared values to studies of urinary GAGs. In severe MPS I patients treated
      with either transplantation or enzyme replacement therapy (ERT), serum HCII-T
      levels never reach the range of normal despite normalization of uGAGs in some
      patients. Some attenuated MPS I patients have normalization of HCII-T but require
      a protracted exposure time relative to the drop in urinary GAGs. Treated MPS II
      patients show a clear correlation of serum HCII-T levels with the presence of
      antibodies to Idursulfase, with antibody positive patients showing an early drop
      in HCII-T levels with eventual increases in levels often to levels above those
      seen at baseline. This is contrasted by a robust and persistent drop in uGAGs.
      Antibody negative MPS II patients show a drop in HCII-T levels on treatment but
      levels never normalize despite normalization of uGAGs. This study highlights the
      utility and biologic relevance of serum HCII-T levels in monitoring therapy in
      these disorders.

PMID- 21732094
TI  - CDG - an update.

PMID- 21732095
TI  - ECMO as a bridge to high-risk rotablation of heavily calcified coronary arteries.
AB  - Mechanical circulatory support (MCS) with short-term ventricular assist devices
      has been used as a bridge to high-risk percutaneous coronary interventions (PCI),
      as well as during interventions and in the post-procedural recovery period.
      Percutaneous extracorporeal membrane oxygenation (ECMO) is used when full
      cardiopulmonary support is necessary due to severe biventricular and pulmonary
      dysfunction. Prompted by two cases of high-risk rotablation of heavily calcified
      coronary arteries where ECMO was used as a bridge to intervention and post
      intervention recovery, we reviewed the bibliography and the new guidelines on
      cardiac revascularization with regard to the utility of MCS devices in high-risk
      PCI cases.

PMID- 21732096
TI  - [Intravascular ultrasound for recognition of atherosclerotic plaques and plaque
      composition. Current state of the diagnostic value].
AB  - Coronary atherosclerosis including acute coronary syndrome (ACS) is the leading
      cause of death in the western world and in the majority of patients is caused by
      plaque rupture in flow-limiting and non-flow-limiting angiographically
      intermediate stenoses. Histopathologic analyses have shown the relationship of
      plaque composition to acute clinical events and therefore to the vulnerability of
      coronary lesions. Knowledge of remodeling processes of the coronary artery has
      focused interest on non-flow-limiting lesions of the coronary tree. Intravascular
      ultrasound (IVUS) can demonstrate discrepancies between the extent of coronary
      atherosclerosis and angiographic imaging by in vivo plaque imaging. In addition
      the spectral analysis of IVUS-derived radiofrequency (RF) data enables more
      precise analysis of the plaque composition and plaque type.As IVUS is best able
      to assess stent underexpansion and malapposition the guidance of catheter-based
      coronary interventions plays a major role in angiographically unclear lesions
      even in the drug-eluting stent era. In the field of percutaneous coronary
      interventions (PCI) IVUS can influence the therapy and therefore optimize the
      stratification of patients.In terms of secondary prevention it is of great
      clinical importance to detect progression of coronary artery disease and moreover
      to predict coronary lesions with significant progression up to ACS. Coronary
      angiography and clinical parameters are poor surrogates to predict future events
      in a broad cohort of patients after PCI. In addition non-invasive imaging fails
      to identify coronary plaques with potential rupture and subsequent ACS. This
      highlights the need to identify potentially high risk lesions. However,
      prospective studies with IVUS-RF imaging to detect lesions that are considered to
      be prone to rupture showed no evidence for catheter-based invasive treatment of a
      non-flow-limiting high risk plaque.In the future the integrated combination of
      multiple technologies (e.g. IVUS-RF and optical coherence tomography) can further
      improve the accuracy of the analysis of high risk lesions.

PMID- 21732097
TI  - Prevalence and outcome of urinary retention after laparoscopic surgery for severe
      endometriosis--does histology provide answers?
AB  - INTRODUCTION AND HYPOTHESIS: Urinary retention after radical laparoscopic surgery
      for severe endometriosis is a clinically relevant complication. We hypothesized a
      relationship between the amount of resected nerves and the occurrence of urinary
      retention. METHODS: We evaluated, retrospectively, a cohort of 221 patients. The
      expression of nerves in the resected specimens was investigated in patients with
      urinary retention and matched controls using standardized immunohistochemistry
      techniques. RESULTS: The prevalence of urinary retention was 4.6% (n = 10).
      Importantly, there was no difference between cases and controls regarding the
      quantity of nerves in the resected specimens. The cumulative probability of 50%
      to overcome urinary retention was reached after 5.6 months. Age was the main risk
      factor for persistent retention (40.3 years with vs. 31.6 years without, p =
      0.01). CONCLUSIONS: In older endometriosis patients, surgical radicality should
      be balanced against preservation of organ function. There is a fairly good chance
      to recover, even after 6 months, which is important for patient counseling.

PMID- 21732098
TI  - Leukoplakia of the bladder: a case report and literature review.
AB  - An 81-year-old woman presented with symptoms of recurrent urinary tract
      infections, urge incontinence and nocturia. Cystoscopy performed revealed a
      whitish plaque lesion on the fundus and right lateral wall of the bladder. The
      histology of the biopsy confirmed the diagnosis of leukoplakia vesicae of the
      bladder. The plan is to follow her up with repeat cystoscopy and biopsy in 6
      months. The literature search revealed very little information on the
      pathogenesis and prognosis of this condition due to its rare occurrence. Analysis
      of the literature signifies the association of chronic irritation due to
      recurrent urinary tract infections being the commonest cause of leukoplakia
      vesicae. The recommended long-term follow-up and surveillance based on the
      literature review is by cystoscopy with or without biopsy.

PMID- 21732099
TI  - Usefulness of retropubic tape for recurrent stress incontinence after
      transobturator tape failure.
AB  - INTRODUCTION AND HYPOTHESIS: This study was conducted to evaluate the
      effectiveness and safety of retropubic suburethral slings (TVT) to treat
      recurrent stress urinary incontinence (SUI) after transobturator tape (TOT)
      failure. METHODS: A descriptive study was performed among women with recurrent
      SUI treated at the Vall d'Hebron University Hospital between January 2006 and
      December 2009. All women were preoperatively evaluated to rule out complications
      of the first sling. Urodynamic testing was performed before and after the TOT
      procedure in all cases. Postoperative follow-up was performed at 1, 6, and 12
      months and yearly thereafter. Outcomes were classified as cured, improved, or
      failed. RESULTS: Twenty-three women were operated on over the study period. The
      median time to reoperation was 12 months (range 6 to 34 months) and the median
      follow-up time was 36.1 months (range 7.8 to 60.2 months). Overall cure and
      improvement rates were 86.4% at 12 and 24 months and 75% at 36 months. Failure
      was found not to be related to time between both sling surgeries. Two cases of
      bladder perforation were recorded (8.7%). Postoperative complications were slight
      and self-limited. De novo urgency occurred in five cases (21.7%). CONCLUSIONS:
      TVT has been found to be effective to treat recurrent SUI after TOT failure in
      the present series with slight side effects.

PMID- 21732100
TI  - Constipation symptoms before and after vaginal and abdominal pelvic
      reconstructive surgery.
AB  - INTRODUCTION AND HYPOTHESIS: This article aims to evaluate how constipation
      symptoms change after pelvic reconstructive surgery using the Patient Assessment
      of Constipation Symptom Questionnaire (PAC-SYM). Our primary hypothesis was that
      constipation would improve after surgery. METHODS: Ninety-four subjects completed
      the PAC-SYM before and 7 weeks after pelvic reconstructive surgery from 2007
      through 2009 inclusive. PAC-SYM scores were compared for the cohort before and 7
      weeks post-surgery and based on route of surgery: vaginal or abdominal. RESULTS:
      Baseline PAC-SYM scores between those undergoing abdominal or vaginal
      reconstructive surgery were not significantly different (0.76 versus 0.83,
      respectively; p = 0.586). Subjects in the vaginal surgery group had a significant
      reduction in PAC-SYM scores, 0.83 to 0.62 (p = 0.049). After abdominal surgery,
      subjects had an increase in abdominal subscale scores, 0.69 to 1.03 (p = 0.012).
      CONCLUSIONS: Women undergoing vaginal prolapse surgery may have a short-term
      improvement in constipation symptoms, while those undergoing abdominal surgery
      have worsening of abdominal constipation symptoms.

PMID- 21732101
TI  - Surgical management of Skene's gland abscess/infection: a contemporary series.
AB  - INTRODUCTION AND HYPOTHESIS: We report our experience with surgical excision for
      treatment of Skene's gland abscess/infection after conservative measures have
      failed. METHODS: A retrospective review of patients that underwent surgical
      excision of Skene's gland abscess/infection by a single surgeon from 06/1995 to
      09/2008 was performed. Patients were separated into groups based on indication
      for procedure. Recurrence rate and success rate were calculated. RESULTS: The
      final study group included 34 patients. After initial excision, 88.2% (30/34) of
      patients had resolution of symptoms. Recurrence of signs and symptoms that
      prompted further treatment occurred in 30% (9/30). In those that recurred, 88.8%
      (8/9) of patients had resolution of symptoms after further therapy. Overall
      success rate in complete resolution of symptoms after all treatment was 85.3%.
      Only patients to fail were in the urethral pain and recurrent UTI groups.
      CONCLUSION: Surgical excision is a safe and effective therapy for the treatment
      of Skene's gland abscess/infection after conservative measures have failed.

PMID- 21732102
TI  - Reversible cortical diffusion restriction, hyperperfusion and T2-hyperintensity
      caused by two different types of epileptic seizure.

PMID- 21732103
TI  - Clinical significance of 2-[18F]fluoro-2-deoxy-D-glucose positron emission
      tomography for the assessment of 131I-metaiodobenzylguanidine therapy in
      malignant phaeochromocytoma.
AB  - PURPOSE: The aim of this study was to evaluate the significance of 2-[18F]fluoro
      2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the assessment of
      the therapeutic response to 131I-metaiodobenzylguanidine (MIBG) in malignant
      phaeochromocytoma. METHODS: We reviewed the records of 11 patients (7 men and 4
      women) with malignant phaeochromocytoma who underwent 131I-MIBG therapy (100-200
      mCi). 18F-FDG PET and serum catecholamine assays were performed 3 months before
      and after the first dose of 131I-MIBG. FDG uptake was evaluated in the observed
      lesions using the maximum standardised uptake value (SUVmax). The average SUVmax
      of all lesions (ASUV) was calculated. If more than five lesions were identified,
      the average SUVmax of the five highest SUVmax (ASUV5) was calculated. The ratio
      of pre- and post-therapy values was calculated for the highest SUVmax (rMSUV),
      ASUV (rASUV), ASUV5 (rASUV5), CT diameter (rCT) and serum catecholamine (rCA).
      Responder (R) and non-responder (NR) groups were defined after a clinical follow
      up of at least 6 months according to changes in symptoms, CT, magnetic resonance
      imaging (MRI) and 123I-MIBG scan. RESULTS: Post-therapy evaluation revealed five
      R and six NR patients. The size of the target lesions was not significantly
      different before and after therapy (p>0.05). However, ASUV and ASUV5 were
      significantly lower in the R group (rASUV 0.64+/-0.18, rASUV5 0.68+/-0.17)
      compared to the NR group (rASUV 1.40+/-0.54, rASUV5 1.37+/-0.61) (p<0.05).
      CONCLUSION: 18F-FDG PET can be potentially used to evaluate the response of
      malignant phaeochromocytoma to 131I-MIBG therapy.

PMID- 21732104
TI  - Is bone marrow uptake of 86Y-DOTATOC routinely observed?

PMID- 21732105
TI  - Androgen deprivation therapy influences the uptake of 11C-choline in patients
      with recurrent prostate cancer: the preliminary results of a sequential PET/CT
      study.
AB  - PURPOSE: The influence of androgen deprivation therapy (ADT) on (11)C-choline
      uptake in patients with prostate cancer (PC) has not yet been clarified. The aim
      of our study was to investigate this issue by means of sequential (11)C-choline
      positron emission tomography (PET)/CT in patients with recurrent PC. METHODS: We
      retrospectively studied 14 recurrent PC patients (mean age 67 years, range 55-82)
      during follow-up after radical prostatectomy (RP) with rising serum prostate
      specific antigen (PSA) levels. All patients had undergone at least two
      consecutive (11)C-choline PET/CT scans: the first (11)C-choline PET/CT before
      commencing ADT and the second (11)C-choline PET/CT after 6 months of ADT
      administration. RESULTS: The mean serum PSA level before ADT was 17.0 +/- 44.1
      ng/ml. After 6 months of ADT administration the PSA value significantly decreased
      in comparison to baseline (PSA = 2.4 +/- 3.1 ng/ml, p < .025). Moreover, before
      starting ADT, 13 of 14 patients had positive (11)C-choline PET/CT for metastatic
      spread, while after 6 months of ADT administration in 9 of 14 patients (11)C
      choline PET/CT became negative. CONCLUSION: These preliminary results suggest
      that ADT significantly reduces (11)C-choline uptake in androgen-sensitive PC
      patients.

PMID- 21732106
TI  - Dynamic 11C-methionine PET analysis has an additional value for differentiating
      malignant tumors from granulomas: an experimental study using small animal PET.
AB  - PURPOSE: We evaluated whether the dynamic profile of L-(11)C-methionine (11C-MET)
      may have an additional value in differentiating malignant tumors from granulomas
      in experimental rat models by small animal positron emission tomography (PET).
      METHODS: Rhodococcus aurantiacus and allogenic rat C6 glioma cells were
      inoculated, respectively, into the right and left calf muscles to generate a rat
      model bearing both granulomas and tumors (n=6). Ten days after the inoculations,
      dynamic 11C-MET PET was performed by small animal PET up to 120 min after
      injection of 11C-MET. The next day, after overnight fasting, the rats were
      injected with 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG), and dynamic 18F-FDG PET
      was performed up to 180 min. The time-activity curves, static images, and mean
      standardized uptake value (SUV) in the lesions were calculated. RESULTS: 11C-MET
      uptake in the granuloma showed a slow exponential clearance after an initial
      distribution, while the uptake in the tumor gradually increased with time. The
      dynamic pattern of 11C-MET uptake in the granuloma was significantly different
      from that in the tumor (p<0.001). In the static analysis of 11C-MET, visual
      assessment and SUV analysis could not differentiate the tumor from the granuloma
      in all cases, although the mean SUV in the granuloma (1.48+/-0.09) was
      significantly lower than that in the tumor (1.72+/-0.18, p<0.01). The dynamic
      patterns, static images, and mean SUVs of 18F-FDG in the granuloma were similar
      to those in the tumor (p=NS). CONCLUSION: Dynamic 11C-MET PET has an additional
      value for differentiating malignant tumors from granulomatous lesions, which
      deserves further elucidation in clinical settings.

PMID- 21732107
TI  - Biodistribution and radiation dosimetry of the 18 kDa translocator protein (TSPO)
      radioligand [18F]FEDAA1106: a human whole-body PET study.
AB  - PURPOSE: [(18)F]FEDAA1106 is a recently developed positron emission tomography
      (PET) radioligand for in vivo quantification of the 18 kDa translocator protein
      [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO
      imaging is expected to be useful for the clinical evaluation of neuroinflammatory
      diseases. The aim of this study was to provide dosimetry estimates for
      [(18)F]FEDAA1106 based on human whole-body PET measurements. METHODS: PET scans
      were performed for a total of 6.6 h after the injection of 183.8 +/- 9.1 MBq of
      [(18)F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on
      coronal images. Estimates of the absorbed doses of radiation were calculated
      using the OLINDA software. RESULTS: Peak uptake was largest in lungs, followed by
      liver, small intestine, kidney, spleen and other organs. Peak values of the
      percent injected dose (%ID) at a time after radioligand injection were calculated
      for the lungs (27.1%ID at 0.2 h), liver (21.1%ID at 0.6 h), small intestine
      (10.4%ID at 6.3 h), kidney (4.9%ID at 1.8 h) and spleen (4.6%ID at 0.6 h). The
      largest absorbed dose was found in the spleen (0.12 mSv/MBq), followed by kidneys
      (0.094 mSv/MBq). The calculated mean effective dose was 0.036 mSv/MBq.
      CONCLUSION: Based on the distribution and dose estimates, the estimated radiation
      burden of [(18)F]FEDAA1106 is moderately higher than that of
      [(18)F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity
      of this radioligand ought to be adjusted in line with regional regulations. This
      result would be helpful for further clinical TSPO imaging studies.

PMID- 21732108
TI  - Do androgens control the uptake of 18F-FDG, 11C-choline and 11C-acetate in human
      prostate cancer cell lines?
AB  - PURPOSE: The aim of this study was to evaluate the impact of androgen ablation
      therapy in different prostate cancer (PCa) cell lines--reflecting different
      stages of the disease--on (18)F-fluorodeoxyglucose (FDG), 11C-choline and 11C
      acetate uptake. METHODS: Uptake experiments were performed in androgen-sensitive
      (LNCaP, PC346C) and independent cell lines (22Rv1, PC346DCC, PC-3) as well as in
      a benign prostatic hyperplasia (BPH-1) cell line. Tracer uptake was assessed
      under androgen ablation. Results of the cancer cell lines were normalized to
      those of BPH-1. To evaluate the effect of androgen on the uptake of 18F-FDG, 11C
      choline and 11C-acetate in PCa cell lines, 10(-8) M R1881, 10(-10) M R1881, the
      combination of 10(-10) M R1881 plus 10(-6) M Casodex or 10(-6) M Casodex alone
      were added in parallel cell cultures 1 day before uptake experiments. Uptake in
      androgen-supplemented cell cultures was compared to the uptake under androgen
      deprivation. Uptake was corrected for cell number using protein content. RESULTS:
      Compared to BPH-1, a higher 18F-FDG uptake was observed only in PC346C cells,
      whereas a higher 11C-choline and markedly increased 11C-acetate uptake was seen
      in all cancer cell lines. Androgens significantly modulated the uptake of 18F-FDG
      in LNCaP, PC346C and 22Rv1 cells, and of 11C-choline in the PC346C and 22Rv1 cell
      line. No androgenic effect on 11C-choline and 18F-FDG uptake was observed in PC-3
      and PC346DCC cells. 11C-Acetate uptake was independent of androgen status in all
      PCa cell lines studied. CONCLUSION: 18F-FDG uptake in PCa cell lines showed the
      highest variability and strongest androgen effect, suggesting its poor potential
      for metabolic imaging of advanced PCa. In contrast to 18F-FDG and 11C-choline,
      11C-acetate uptake was unaffected by androgens and thus 11C-acetate seems best
      for monitoring PCa progression.

PMID- 21732109
TI  - Relationship between retinal nerve fiber layer thickness and driving ability in
      patients with human immunodeficiency virus infection.
AB  - BACKGROUND: The aim of this work is to study the possible association between
      retinal nerve fiber layer (NFL) thickness and driving ability. METHODS: Thirty
      eight drivers including 22 HIV-positive (HIV+) and 16 age-matched HIV-negative
      controls participants underwent a full ophthalmologic evaluation, including
      assessment of retinal NFL thickness. In the undilated state with standard optical
      correction and under standard illumination they also completed a computer-based,
      wide field-of-view driving simulation in which they were to obey traffic laws,
      engage in crash avoidance, and pass slower automobiles. Crashes, speeding and
      traffic light tickets, and off-road excursions contributed to a weighted score of
      driving errors. RESULTS: HIV-seropositive participants had a significantly higher
      weighted error score than control participants (18.4 [9.2] vs. 11.1 [4.5], p =
      0.006). NFL thickness was significantly correlated with driving errors (r = 
      0.51, p = 0.025); there was a trend for participants with a CD4 nadir <100 to
      have more errors than those with a nadir >100 (29.7 [13.2] vs. 19.3 [8.4], p =
      0.056). The highest number of driving errors occurred in individuals with both
      CD4 <100 and NFL thickness <80. CONCLUSIONS: Driving ability may be impacted by
      reductions in retinal nerve fiber layer thickness. Physicians should consider the
      potential impact that more complex ophthalmologic conditions in HIV-infected
      patients may have on driving performance.

PMID- 21732110
TI  - Three-year canaloplasty outcomes for the treatment of open-angle glaucoma:
      European study results.
AB  - BACKGROUND: To report 3-year results investigating the safety and efficacy of
      canaloplasty, a procedure involving circumferential viscodilation of Schlemm's
      canal and tensioning of the inner canal wall to treat open-angle glaucoma.
      METHODS: This was a prospective, multi-center, interventional study of 109 eyes
      of 109 adult, open-angle glaucoma patients undergoing canaloplasty or combined
      cataract-canaloplasty surgery. Qualifying preoperative intraocular pressures
      (IOP) were at least 16 mmHg with historical IOPs of at least 21 mmHg with or
      without medical therapy. A flexible microcatheter was used to viscodilate the
      full circumference of the canal and to place a trabecular tensioning suture.
      Primary outcome measures included IOP, glaucoma medication usage, and adverse
      events. RESULTS: Eyes with canaloplasty showed a mean baseline IOP of 23.0 +/-
      4.3 mmHg and mean glaucoma medication usage of 1.9 +/- 0.7 medications, which
      decreased to a mean IOP of 15.1 +/- 3.1 mmHg on 0.9 +/- 0.9 medications at 3
      years postoperatively. Eyes with combined cataract-canaloplasty surgery showed a
      mean baseline IOP of 24.3 +/- 6.0 mmHg on 1.5 +/- 1.2 medications, which
      decreased to a mean IOP of 13.8 +/- 3.2 mmHg on 0.5 +/- 0.7 medications at 3
      years. Intraocular pressure and medication use results for all study eyes were
      significantly decreased from baseline (p <0.00001) at all intervals. Late
      postoperative complications included cataracts (19.1%) and transient IOP
      elevation (1.8%). CONCLUSIONS: Canaloplasty demonstrated significant and
      sustained IOP reductions accompanied by an excellent short- and long-term safety
      profile in adult patients with open-angle glaucoma.

PMID- 21732111
TI  - Real-time polymerase chain reaction and intraocular antibody production for the
      diagnosis of viral versus toxoplasmic infectious posterior uveitis.
AB  - PURPOSE: The aim of this work was to determine the diagnostic performance of real
      time polymerase chain reaction (RT-PCR) and to assess intraocular specific
      antibody secretion (Goldmann-Witmer coefficient) on samples from patients with
      signs of posterior uveitis presumably of infectious origin and to target the use
      of these two biologic tests in the diagnostic of Toxoplasma/viral Herpesviridae
      posterior uveitis by the consideration of clinical behavior and delay of
      intraocular sampling. METHODS: Aqueous humour and/or vitreous fluid were
      collected from patients suspected of having posterior uveitis of infectious
      origin at presentation (140 samples). The diagnosis was confirmed by
      quantification of antibodies with the Goldmann-Witmer coefficient (GWC) and for
      detection of Herpesviridae and Toxoplasma gondii genomes with RT-PCR. Forty-one
      patients had final diagnosis of uveitis of non-Toxoplasma/non-viral origin and 35
      among them constituted the control group. The main outcome measures were
      sensitivity, specificity, and positive and negative predictive values (PPV and
      NPV). RESULTS: When pre-intraocular testing indication was compared with final
      diagnosis, GWC was a more sensitive and specific method than RT-PCR, and was
      successful in detecting T. gondii, especially if the patient is immunocompetent
      and the testing is carried out later in the disease course, up to 15 months. For
      viral Herpesviridae uveitis, the sensitivity and PPV of PCR evaluation was higher
      than detected with GWC with respectively 46% compared with 20% for sensitivity
      and 85% versus 60% for PPV. In either viral retinitis or toxoplasmosis infection,
      RT-PCR results were positive from 24 h, although GWC was not significant until 1
      week after the onset of signs. In toxoplasmosis patients, positive RT-PCR results
      were statistically correlated with the chorioretinitis area (more than three disc
      areas; p = 0.002), with the age older than 50 (p = 0.0034) and with a clinical
      anterior inflammation (Tyndall >=1/2+) and panuveitis; (p = 0.0001). CONCLUSIONS:
      For the diagnosis of viral or toxoplasmosis-associated intraocular inflammation,
      the usefulness of laboratory diagnosis tools (RT-PCR and GWC) depends on
      parameters other than the sensitivity of the tests. Certain patient
      characteristics such as the age of the patients, immune status, duration since
      the onset of symptoms, retinitis area, predominant site and extent of
      inflammation within the eye should orientate the rational for the choice of
      laboratory testing in analysis of intraocular fluids.

PMID- 21732112
TI  - A photothermal model of selective photothermolysis with dynamically changing
      vaporization temperature.
AB  - The theory of selective photothermolysis (SP) is used in many fields of laser
      surgery and medicine. As several parameters and a number of complicated
      photothermal interactions are involved in SP, numerical simulations have been
      providing an important and effective way in SP studies. However, with different
      photothermal models of SP, simulated results differ considerably. In addition,
      insufficient attention has been paid to tissue pressure variation during SP in
      these models, so that vessel rupture and other clinical phenomena cannot be
      explained. A novel photothermal model of SP was proposed using a Monte Carlo
      method to simulate the laser transport in the tissue, a heat transfer equation
      with dynamically changing vaporization temperature to calculate the temperature
      distribution, and the Arrhenius equation to predict the thermal damage. A factor
      of trapped vaporized tissue water k was introduced to describe the effects on
      tissue pressure, temperature, and other related parameters. It was shown that the
      simulation results are affected significantly by k. Temperature and thermal
      damage volume are almost identical, respectively, to those obtained with models
      with vaporization at 100 degrees C and models without vaporization when k = 0 and
      1, while thermal damage volume is close to that obtained with models of
      vaporization at 110 degrees C and 130 degrees C, respectively, when k = 0.022 and
      k = 0.18. To some extent, the current models without vaporization and models with
      vaporization at constant temperature can be regarded as special cases at specific
      situations of this new photothermal model of SP. In addition, more descriptive
      simulation results, such as temperature, thermal damage, and pressure, are
      accessible with this model, although the accuracy depends on the value of k, the
      estimation of which is planned as future work.

PMID- 21732113
TI  - Stability of dental implants after irradiation with an 830-nm low-level laser: a
      double-blind randomized clinical study.
AB  - Little is known about the benefits of low-level laser therapy (LLLT) on
      improvement of stability of dental implants. The aim of this randomized clinical
      study was to assess the LLLT effect on implants stability by means of resonance
      frequency analysis (RFA). Thirty implants were distributed bilaterally in the
      posterior mandible of eight patients. At the experimental side, the implants were
      submitted to LLLT (830 nm, 86 mW, 92.1 J/cm(2), 0.25 J, 3 s/point, at 20 points),
      and on the control side, the irradiation was simulated (placebo). The first
      irradiation was performed in the immediate postoperative period, and it was
      repeated every 48 h in the first 14 days. The initial implant stability quotient
      (ISQ) of the implants was measured by means of RFA. New ISQ measurements were
      made after 10 days, 3, 6, 9, and 12 weeks. The initial ISQ values ranged from 65
      84, with a mean of 76, undergoing a significant drop in stability from the 10th
      day to the 6th week in the irradiated group, and presenting a gradual increase
      from the 6th to the 12th week. The highest ISQ values were observed on the 10th
      day in the irradiated group, and the lowest in the 6th week in both groups. Under
      the conditions of this study, no evidence was found of any effect of LLLT on the
      stability of the implants when measured by RFA. Since high primary stability and
      good bone quality are of major relevancy for a rigid bone-implant interface,
      additional LLLT may have little impact macroscopically.

PMID- 21732114
TI  - Effect of 980-nm GaAlAs diode laser irradiation on healing of extraction sockets
      in streptozotocin-induced diabetic rats: a pilot study.
AB  - Low-level laser irradiation can promote the healing process in soft and hard
      tissue but the precise mechanisms are unclear. In this study, we examined the
      effect of LLLT (low-level laser therapy) on the healing of extraction sockets in
      diabetic and healthy rats. Forty-eight Sprague-Dawley rats were divided into
      normal (n = 24) and diabetic (n = 24) rats, and streptozotocin (STZ) injection
      was used to induce diabetes in the latter. The left and right maxillary first
      molars of all the rats were extracted. In the non-diabetic rats, the left
      extraction sockets were not irradiated (group 1) and the right ones were
      irradiated daily for 3, 5, 7, and 14 days after extraction with a galium-aluminum
      arsenide (GaAlAs) diode laser (group 2), and in the diabetic rats, similarly the
      left ones were not irradiated (group 3) and the right ones were irradiated (group
      4). Specimens acquired at these intervals were examined by hematoxylin and eosin
      (H&E) staining and reverse transcription polymerase chain reaction (RT-PCR).
      Histological observations and gene expression analyses revealed that groups 2
      (normal rats with LLLT) and 4 (diabetic rats with LLLT) showed faster initial
      healing and more new alveolar bone formation than group 1 (normal rats without
      LLLT) and group 3 (diabetic rats without LLLT), respectively. We conclude that
      980-nm GaAlAs low-intensity diode laser irradiation is beneficial for the initial
      stages of alveolar bone healing and for further calcification in both diabetic
      and normal rats when applied every day at a dose of 13.95 J/cm(2) for 60 s.

PMID- 21732115
TI  - Noninvasive visualization of intraepidermal and subepidermal blisters in
      vesiculobullous skin disorders by in vivo reflectance confocal microscopy.

PMID- 21732116
TI  - A mysterious term hippocampus involved in learning and memory.

PMID- 21732117
TI  - Absence of exon 17 c.2970-2872delAAT mutation in Turkish NF1 patients with mild
      phenotype.
AB  - INTRODUCTION: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder
      characterized by cafe-au-lait spots, neurofibromas, skinfold freckles, Lisch
      nodules, bone deformities, learning disabilities, and predisposition to
      neoplasms. It is caused by various mutations of the NF1 gene. Recently a 3-bp in
      frame deletion in exon 17, c.2970-2972 delAAT mutation, has been associated with
      a milder phenotype of NF1 manifesting with pigmentary skin changes only.
      MATERIALS AND METHODS: We therefore analyzed 35 NF1 patients without
      neurofibromas, learning problems, or bone lesions (19 familial, 16 sporadic, age
      7-44 years) for exon 17 mutations by DNA sequencing. RESULTS: We did not find the
      c.2970-2972 delAAT mutation in this group but identified two base changes in exon
      17 (c.2989A>G and c.2894T>A), whether these two novel mutations are related to a
      mild phenotype remains to be confirmed in further studies. Our results suggest
      the reported phenotypic associations may not be valid for all populations.

PMID- 21732118
TI  - Cerebellar mutism: definitions, classification and grading of symptoms.

PMID- 21732119
TI  - Diffusion-weighted imaging and pathological correlation in pediatric
      medulloblastomas-"They are not always restricted!".
AB  - INTRODUCTION: Some investigators have suggested that medulloblastomas can be
      distinguished from other cerebellar neoplasms by demonstrating "restricted
      diffusion" on the Apparent Diffusion Coefficient (ADC) map obtained from
      diffusion-weighted imaging (DWI) sequences on magnetic resonance imaging.
      Previous authors have postulated that this observed restricted diffusion is a
      reflection of very high cell density. There has been a tendency to assert that
      pediatric medulloblastoma uniformly demonstrates restricted diffusion on DWI.
      However, our clinical observation has been that there are pediatric
      medulloblastomas that exhibit normal or even increased diffusion on DWI. The
      current study was undertaken primarily to determine whether restricted diffusion
      is uniformly present in pediatric medulloblastoma and secondly to look for
      pathological features that might distinguish medulloblastomas with and without
      restricted diffusion. METHODS: The DWI characteristics of pathologically
      confirmed medulloblastomas diagnosed at our institution were retrospectively
      reviewed. The ADC was obtained in two non-overlapping, solid, non-hemorrhagic,
      non-necrotic regions of tumor and averaged. An ADC below 1 * 10(-3) mm(2)/s was
      considered to represent restricted diffusion. A detailed pathologic review of
      each tumor was conducted. RESULTS: Ten cases of medulloblastoma were reviewed, of
      which two demonstrated average ADCs above 1 * 10(-3) mm(2)/s (1.223 and 1.169 *
      10(-3) mm(2)/s, respectively), indicating no restricted diffusion. Pathologic
      review revealed that both of these non-restricting cases displayed a lack of
      reticulin deposition by light microscopy. CONCLUSION: DWI does not appear to be
      an entirely reliable means of distinguishing medulloblastomas from other
      cerebellar neoplasms. Histologically, restricted diffusion in medulloblastomas
      may be related to reticulin deposition.

PMID- 21732120
TI  - Socioeconomic impact on device-associated infections in limited-resource neonatal
      intensive care units: findings of the INICC.
AB  - PURPOSE: To evaluate the impact of country socioeconomic status and hospital type
      on device-associated healthcare-associated infections (DA-HAIs) in neonatal
      intensive care units (NICUs). METHODS: Data were collected on DA-HAIs from
      September 2003 to February 2010 on 13,251 patients in 30 NICUs in 15 countries.
      DA-HAIs were defined using criteria formulated by the Centers for Disease Control
      and Prevention. Country socioeconomic status was defined using World Bank
      criteria. RESULTS: Central-line-associated bloodstream infection (CLA-BSI) rates
      in NICU patients were significantly lower in private than academic hospitals
      (10.8 vs. 14.3 CLA-BSI per 1,000 catheter-days; p < 0.03), but not different in
      public and academic hospitals (14.6 vs. 14.3 CLA-BSI per 1,000 catheter-days; p =
      0.86). NICU patient CLA-BSI rates were significantly higher in low-income
      countries than in lower-middle-income countries or upper-middle-income countries
      [37.0 vs. 11.9 (p < 0.02) vs. 17.6 (p < 0.05) CLA-BSIs per 1,000 catheter-days,
      respectively]. Ventilator-associated-pneumonia (VAP) rates in NICU patients were
      significantly higher in academic hospitals than in private or public hospitals
      [13.2 vs. 2.4 (p < 0.001) vs. 4.9 (p < 0.001) VAPs per 1,000 ventilator days,
      respectively]. Lower-middle-income countries had significantly higher VAP rates
      than low-income countries (11.8 vs. 3.8 per 1,000 ventilator-days; p < 0.001),
      but VAP rates were not different in low-income countries and upper-middle-income
      countries (3.8 vs. 6.7 per 1,000 ventilator-days; p = 0.57). When examined by
      hospital type, overall crude mortality for NICU patients without DA-HAIs was
      significantly higher in academic and public hospitals than in private hospitals
      (5.8 vs. 12.5%; p < 0.001). In contrast, NICU patient mortality among those with
      DA-HAIs was not different regardless of hospital type or country socioeconomic
      level. CONCLUSIONS: Hospital type and country socioeconomic level influence DA
      HAI rates and overall mortality in developing countries.

PMID- 21732121
TI  - The public health impact of major depression: a call for interdisciplinary
      prevention efforts.
AB  - Major depression is a consequential public health problem in the United States.
      Depression has long been recognized as an important target of intervention in
      psychology and psychiatry, but these fields have focused efforts primarily on
      treatment rather than prevention. Although effective preventive interventions
      targeting high-risk groups have been developed, they have thus far had poor reach
      and sustainability in the community. The development of sustainable preventive
      interventions that have the potential to impact population health represents a
      critical goal for the field. To this end, a research agenda incorporating the
      perspectives of both mental health disciplines and public health is proposed as a
      guide for future depression prevention research. Increased interdisciplinary
      collaboration between mental health disciplines and public health is recommended
      to develop, enact, and evaluate multilevel preventive interventions aimed at
      reducing the population health burden of major depression.

PMID- 21732122
TI  - Growth patterns of lung metastases from sarcomas.
AB  - Complete resection of pulmonary metastases from sarcomas is an established method
      of treatment. While resection margins are well described for primary sarcoma
      lesions, minimal knowledge is available about margins and factors influencing
      local tumour control in the lung. The objective of the present study was to
      describe intrapulmonary patterns of growth for sarcoma metastases as a basis for
      planning resections. From January 2006 to January 2009, we retrospectively
      analysed 261 resected pulmonary sarcoma metastases from 52 patients. All
      metastases were reviewed for histological characteristics and resection margins.
      Metastases characterised by a solid, well-defined tumour mass were found in 127
      of 261 metastases (48.7%). Interstitial spread (39.8%), vascular infiltration
      (20.7%), satellite nodules (16.1%) and lymphangitic spread (10.7%) were
      identified as aggressive histological growth characteristics. Forty-five of 52
      patients (86.5%) had metastases with a mitotic index of 10 or more per 10 HPF,
      underlining their high-grade malignant potential. The following characteristics
      of aggressive intrapulmonary growth were highly correlated with each other:
      interstitial growth and lymphangitic spread (p = 0.002), interstitial growth and
      vascular infiltration (p < 0.001), vascular infiltration and satellite nodules (p
      = 0.009), interstitial growth and pleural invasion (p = 0.004); by contrast, the
      presence of a fibrous pseudocapsule (17.2%) was not associated with aggressive
      growth patterns. Almost half of all pulmonary sarcoma metastases could be
      identified with aggressive patterns of local growth, and only 17.2% are
      surrounded by a pseudocapsule which might allow safe resection margins.

PMID- 21732123
TI  - Pachydermia verrucosa...of the (very) bad kind!

PMID- 21732124
TI  - Expression of Kruppel-like factor 5 in gastric cancer and its clinical
      correlation in Taiwan.
AB  - Kruppel-like factors (KLFs), highly conserved zinc-finger proteins, play either
      anti- or pro-proliferation roles in different human cancers through regulating a
      wide range of genes' expression. Here, we investigated the expression of KLF5 in
      gastric cancers and its correlation with clinicopathological parameters and
      overall survival rates. In this study, KLF5 expression was measured by an
      immunohistochemical microarray assay of tissue taken from 76 surgical specimens.
      Higher KLF5 expression was significantly associated with lower tumor grade (P <
      0.001). Nuclear staining of the KLF5 expression was significantly associated with
      a higher tumor grade (P = 0.000), higher clinical stage (P = 0.019), lymph node
      status (P = 0.016), and 2-year survival (P = 0.017). Patients with nuclear
      staining of KLF5 had a significantly lower disease-free survival rate compared to
      patients with negative nuclear staining, as defined by a log-rank test (P =
      0.041). Our results revealed that KLF5 may play an oncogenetic role in gastric
      carcinogenesis.

PMID- 21732125
TI  - Reinforcement of pericranium as a dural substitute by fibrin sealant.
AB  - BACKGROUND: For dural plasty, several kinds of substitute materials are used
      clinically. Among these materials, pericranium is often used as a dural
      substitute since it is autologous and easy to harvest. However, it is rather thin
      and fragile, which makes it difficult to suture onto peripheral dura mater,
      especially when the defect is large. OBJECTIVE: We present a simple method of
      reinforcing the pericranium with fibrin sealant, which facilitates easier
      handling and suturing of the pericranium. METHODS: Fifteen patients who underwent
      surgical removal of meningioma, metastatic brain tumor and glioma attached to the
      dura mater were included in this analysis. To close the defects, we use 'fibrin
      sealed pericranium'. Herein we describe the method we employed in these cases.
      First, a standard skin flap is made by dissecting the subgaleal layer, leaving
      the periosteum on the bone. Second, fibrin sealant is evenly applied to the
      pericranium. Finally, the pericranium is cut along the reinforced area and
      dissected from the bone. The harvested pericranium is then used for closure of
      the dural defect. Some of these patients received further treatment as needed
      according to each pathology. The fibrin-sealed pericranium was examined
      histopathologically. RESULTS: Fibrin-sealing of pericranium made it durable
      enough to be handled and sutured easily. There were no significant complications
      or treatment failures, such as infection or CSF leakage. CONCLUSIONS:
      Reinforcement of the pericranium with fibrin sealant is a simple and easy method
      to reduce the stress of dural plasty.

PMID- 21732126
TI  - How eloquent is eloquent?

PMID- 21732127
TI  - Resection frequency map after awake resective surgery for non-lesional
      neocortical epilepsy involving eloquent areas.
AB  - BACKGROUND: The resection of eloquent areas is challenging due to postoperative
      neurological deficits. The purpose of this study was to assess the efficacy and
      risk of awake brain surgery for non-lesional epilepsy involving the eloquent
      areas or their adjacent areas and to advocate the generation of a resection
      frequency map. METHODS: We enrolled 55 patients who underwent awake surgery
      between 1994 and 2007 for non-lesional epilepsy involving the primary sensori
      motor or language areas. All patients underwent two-staged operations including
      subdural electrode monitoring and awake resective surgery. For each case, the
      preoperative and postoperative images were spatially normalized and compared on a
      standard atlas, and the resection map was then computed by summing up each
      resected area on the atlas. RESULTS: The postoperative seizure outcome was Engel
      class I in 27 patients (49.1%), II in nine (16.4%), III in 14 (25.5%) and IV in
      five (9.1%). Ten patients (18.2%) experienced postoperative neurological deficits
      including seven transient (12.7%) and three permanent, but mild ones (5.5%). The
      neurological complication rate of purely eloquent area resection was 36.8%
      (7/19). The resection frequency map computed in this study showed that the
      resection of eloquent areas was tolerable, with the exception of the Broca's
      area. CONCLUSIONS: Awake resective surgery with intraoperative brain mapping is
      an effective and safe treatment option for non-lesional epilepsy involving
      eloquent areas. The resection frequency map can show the resected area of a group
      as well as individuals and provide an objective measure of neurological risk.

PMID- 21732128
TI  - Impact of hepatic clearance of endotoxin using endotoxin activity assay.
AB  - BACKGROUND: Endotoxin (Et) in the portal vein blood is processed by the hepatic
      reticuloendothelial system, and therefore, it is possible that the hepatic
      clearance of Et may become a biological index for liver function. In this study,
      Et levels of preoperative peripheral and portal vein blood at the time of liver
      transplantation (LT) were measured in order to study the meaning. METHODS: The
      study population comprised 19 patients in whom pediatric living donor LT was
      performed. In the preoperative peripheral and the portal vein blood at the time
      of LT, we measured Et activity (EA) by the Et activity assay (EAA) and the
      Limulus amebocyte lysate (LAL) method. RESULTS: The preoperative peripheral vein
      blood showed a low EA in all cases. In the EA of the peripheral and the portal
      vein blood, the latter showed a significantly high level (p = 0.049). With the
      LAL method, 5.3% (2/38) of patients were positive for Et. CONCLUSIONS: The EAA is
      considered to be superior to the LAL method for the detection of Et, even in low
      endotoxinemia, and is also capable of elucidating the Et kinetics by accurately
      reflecting hepatic clearance.

PMID- 21732130
TI  - Two RFID-based solutions for secure inpatient medication administration.
AB  - Medication error can easily cause serious health damage to inpatients in
      hospital. Consequently, the whole society has to spend huge amount of extra
      resources for additional therapies and medication on those affected inpatients.
      In order to prevent medication errors, secure inpatient medication administration
      system is required in a hospital. Using RFID technology, such administration
      system provides automated medication verification for inpatient's medicine doses
      and generates corresponding medication evidence, which may be audited later for
      medical dispute. Recently, Peris-Lopez et al. (Int. J. Med. Inform., 2011)
      proposed an IS-RFID system to enhance inpatient medication safety. Nevertheless,
      IS-RFID system does not detect the denial of proof attack efficiently and the
      generated medication evidence cannot defend against counterfeit evidence
      generated from the hospital. That is, the hospital possesses enough privilege
      from the design of IS-RFID system to modify generated medication evidence
      whenever it is necessary. Hence, we design two lightweight RFID-based solutions
      for secure inpatient medication administration, one for online verification
      environment and the other for offline validation situation, to achieve system
      security on evidence generation and provide early detection on denial of proof
      attack.

PMID- 21732131
TI  - Subcellular FIH-1 expression patterns in invasive breast cancer in relation to
      HIF-1alpha expression.
AB  - BACKGROUND: Hypoxia Inducible Factor-1alpha (HIF-1alpha) expression in breast
      cancer is associated with a poor clinical outcome. HIF-1alpha shows two
      expression patterns: the canonical poor prognosis hypoxia-related perinecrotic
      pattern and a diffuse expression pattern that seems to have less downstream
      effects and is clearly associated with poor survival. Factor-inhibiting hypoxia
      inducible factor 1 (FIH-1) inhibits HIF-1 activity by hydroxylating the C
      terminal trans-activation domain of the HIF-1alpha subunit, thus preventing HIF-1
      from recruiting co-activators CPB/p300, which are important for inducing the
      transcription of target genes. The aim of this study was to investigate the
      expression patterns of FIH-1 in breast cancer and evaluate the relationship
      between FIH-1 and HIF-1alpha expression in breast cancer as a possible
      explanation for apparently less downstream effects of diffuse HIF-1alpha
      expression. METHODS: Tissue sections from 92 consecutive invasive breast
      carcinomas were stained by immunohistochemistry for FIH-1, HIF-1alpha, glucose
      transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX). RESULTS: 45 cases
      overexpressed HIF-1alpha, 5 of which in a perinecrotic fashion while FIH-1 was
      positive in 73 of the 92 cases studied. Contrary to our expectations, three out
      of five cases with perinecrotic HIF-1alpha expression were also positive for
      FIH1. Cytoplasmic FIH-1 correlated with HIF-1alpha expression (P = 0.03) and
      tumor grade (P = 0.01). HIF-1alpha overexpression predicted poorer prognosis as
      usual (P = 0.02). FIH expression had no additional prognostic value to HIF
      1alpha. CONCLUSIONS: FIH1 is expressed in the majority of invasive breast
      carcinomas and shows distinct subcellular localization patterns. FIH-1 expression
      does not seem to explain the proposed functional differences between diffuse and
      perinecrotic HIF-1alpha expression in breast cancer.

PMID- 21732133
TI  - Bereavement, doubt, and the loved body: a 9/11 meditation.
AB  - The experience of firefighters at the site of the World Trade Center collapse,
      especially their fanatic devotion to the task of body recovery, is examined in an
      effort to understand their motivations. The need to make physical contact with
      the body of a deceased loved one is considered in light of the Gospel accounts of
      the disciples' contact with the resurrected body of Jesus. The need for sensory
      contact with the loved body is discussed as a crucial element in the process of
      grief, leading to the process of recovery from traumatic loss.

PMID- 21732134
TI  - The First Church of Christ, Pragmatist: Christian Science and responsible
      optimism.
AB  - A common criticism of Christian Science is that it is neither Christian nor
      scientific. American psychologist and philosopher William James would not, I
      believe, share this view, even though he does make critical comments about
      Christian Science's orginator and her dogmatic followers. Following a suggestion
      of James, I distinguish two types of critical inquiry into Christian Science-
      outsider criticism and insider criticism--and show that the latter yields the
      better results. A pragmatic version of Christian Science can be offered that is
      distinct both from the myopic critics who malign it and from the dogmatic
      followers who recklessly adhere to it.

PMID- 21732135
TI  - Study on the enzymatic degradation of PBS and its alcohol acid modified
      copolymer.
AB  - Enzymatic hydrolytic degradation of polybutylene succinate (PBS),
      poly(polybutylenesuccinate-co-1,4-cyclohexane dimethanol) (PBS/CHDM) and
      poly(polybutylene succinate-co-diglycolic acid) (PBS/DGA) in mixed solvent of
      tetrahydrofuran (THF) and toluene was examined. Lipase was used as catalyst to
      degrade polymers with molecular weight of more than 100,000, and the molecular
      weight of products ranged from hundreds to thousands. Thermal decomposition
      temperatures of all products were below 250 degrees C. The degradation products
      of both PBS/CHDM and PBS/DGA showed two melting points at about 85 and 99 degrees
      C. Mass spectrometry (MS) was employed to obtain the molecular weight of
      oligomers extracted from the products, which proved to be low-polyesters with the
      molecular weight of less 1,000. The butanediol (BDO) monomer was found in
      PBS/CHDM degradation product for the first time.

PMID- 21732136
TI  - Heme-mediated binding of alpha-casein to ferritin: evidence for preferential
      alpha-casein binding to ferrous iron.
AB  - Bovine milk alpha-casein was identified as a ferritin-binding protein, and
      ferritin is known to be a heme-binding protein. In this study, we found that the
      binding of alpha-casein to bovine spleen ferritin in vitro was blocked by hemin,
      but not by iron-free hemin (protoporphyrin IX) or zinc-protoporphyrin IX,
      suggesting that the presence of iron in heme play a key role in this interaction.
      Indeed, the binding of alpha-casein to ferritin and biotinylated hemin was
      inhibited by adding excess ferrous ammonium sulfate (FAS). To further elucidate
      the binding mechanism of alpha-casein to biotinylated hemin, Ferrozine and
      nitrilotriacetic acid (NTA) were used as ferrous and ferric iron chelators,
      respectively. FAS-mediated inhibition of alpha-casein to biotinylated hemin was
      neutralized with Ferrozine, but not NTA, while FAS- as well as ferric chloride
      mediated inhibition in their interaction was neutralized by NTA. The following
      ions also inhibited alpha-casein-biotinylated hemin binding in order of potency
      of inhibition: FAS (Fe(2+)) << ferric chloride (Fe(3+)) < copper sulfate (Cu(2+))
      < zinc sulfate (Zn(2+)) < manganese chloride (Mn(2+)) < calcium chloride (Ca(2+))
      < magnesium sulfate (Mg(2+)). These results suggests that the binding of alpha
      casein to ferritin is heme-mediated through direct binding of alpha-casein to
      iron in the heme on the surface of ferritin molecule, and that alpha-casein
      preferentially binds Fe(2+) compared with any other metal ions, including Fe(3+).

PMID- 21732137
TI  - Usefulness of transcription-reverse transcription concerted reaction method for
      detecting circulating tumor cells in patients with colorectal cancer.
AB  - PURPOSE: The CellSearch system (Veridex, LLC) is useful for detecting circulating
      tumor cells (CTCs) in various carcinomas, including colorectal cancer (CRC);
      however, there are some problems associated with its clinical use. A
      transcription-reverse transcription concerted reaction (TRC) method, which is a
      PCR-based technique producing more stable and reliable results, because it is a
      more simplified process compared with the conventional techniques, has been
      introduced for detecting micrometastasis in some carcinomas. We aimed to
      demonstrate the effectiveness of TRC method in the CTC detection. METHODS: We
      compared the two methods for the sensitivity for CTC detection using the colon
      cancer cell line and 42 whole-blood samples from patients with advanced or
      metastatic CRC. Furthermore, 25 patients with metastatic CRC were enrolled to
      investigate the correlation between CTC detection and prognosis in both methods.
      RESULTS: The sensitivity of the TRC method was similar to that of the CellSearch
      system. The overall survival rate was significantly worse in the patients
      diagnosed as CTC-positive by the TRC method than in those diagnosed as CTC
      negative; this finding was similar to the prognosis indicated by the CellSearch
      system. However, clinically, the TRC method could detect CTCs more rapidly and at
      a reduced cost compared with the CellSearch system. CONCLUSIONS: The TRC method
      seems to be a useful alternative to the CellSearch system for clinically
      detecting CTCs in patients with metastatic CRC.

PMID- 21732138
TI  - Moving away from axillary lymph node dissection indicates practice-changing
      trials.

PMID- 21732139
TI  - Inhibition of heat shock protein response enhances PS-341-mediated glioma cell
      death.
AB  - BACKGROUND: Previous study indicated that PS-341 induces cell death via JNK
      pathway in vitro in glioma. However, suppressing proteasome complex by PS-341 may
      induce expression of heat shock proteins (HSPs), which confer potential
      protection against cellular stress. In this study, we explored whether induction
      of HSPs could impair PS-341-induced cell death and whether inhibition of HSPs
      could enhance cell damage induced by PS-341 in glioma cells. METHODS: HSP
      expression in glioma cells was modulated by HSP inhibitor, sublethal heat, or
      knockdown of heat shock factor1 (HSF1), then PS-341-induced cell damage was
      examined by different methods. Similar experiments were also performed in HSF1+/+
      and HSF1-/- cells. HSP70 expression and HSF1 nuclear localization were compared
      between glioma and normal brain tissues. RESULTS: HSP level was upregulated
      mediated by HSF1 when glioma cells were treated with PS-341. PS-341-mediated cell
      damage could be significantly augmented by HSP inhibition. Furthermore, HSP70
      expression and HSF1 nuclear localization were much more abundant in gliomas than
      in normal brain tissues. CONCLUSIONS: Our results demonstrated that HSP70
      impaired cell death induced by PS-341 in glioma cells. Administration of PS-341
      in combination with either HSP70 inhibitor or HSF1 knockdown may act as a new
      approach to treatment of glioma.

PMID- 21732140
TI  - Antigen-directed cancer surgery for primary colorectal cancer: 15-year survival
      analysis.
AB  - BACKGROUND: Tumor-associated glycoprotein-72 (TAG-72) is a mucin-like high
      molecular-weight glycosylated protein complex overexpressed by many
      adenocarcinomas. Antigen-directed cancer surgery using radiolabeled anti-TAG-72
      murine monoclonal antibodies (muMAbs) has been previously investigated for
      colorectal cancer. Survival analysis of primary colorectal cancer patients with a
      minimum of 15-year follow-up after antigen-directed cancer surgery was performed
      to assess the impact of complete surgical resection of all detectable
      radiolabeled anti-TAG-72 muMAb. METHODS: Survival analysis was performed on 92
      patients (study group) with primary colorectal cancer (July 1990 to August 1995)
      treated with antigen-directed cancer surgery using (125)I-labeled anti-TAG-72
      muMAb. The study group was subdivided into those with no detectable TAG-72
      antigen-bearing tissues (TAG-72 negative, N=33) and those with persistent
      detectable TAG-72 antigen-bearing tissues (TAG-72 positive, N=59) at completion
      of surgery. Comparisons were made with a control group (546 patients) from the
      same time period. RESULTS: Study group and control group were demographically
      similar, as were TAG-72-negative subgroup and TAG-72-positive subgroup. TAG-72
      negative subgroup had significantly improved median survival (8.8 versus 2.5
      years; P=0.005) and time-dependent survival (45.4% versus 22.0% at 10 years;
      P=0.002 and 39.4% versus 20.3% at 15 years; P=0.003) compared with TAG-72
      positive subgroup. TAG-72 positivity was as an independent predictor of long-term
      mortality risk, when controlled for pathologic stage of disease. CONCLUSIONS:
      Absence of detectable TAG-72 antigen within the surgical field at completion of
      antigen-directed cancer surgery for primary colorectal cancer is of significant
      prognostic value, conferring a long-term survival advantage to those in whom
      complete surgical removal of all tissues with detectable radiolabeled anti-TAG-72
      muMAb was accomplished.

PMID- 21732141
TI  - Expression of IGF1R is associated with tumor differentiation and survival in
      patients with lung adenocarcinoma.
AB  - PURPOSE: The insulin-like growth factor 1 receptor (IGF1R) is widely expressed in
      normal tissues and many malignancies in humans. We investigated the clinical
      significance of the expression of the IGF1R gene in human lung adenocarcinoma.
      METHODS: A total of 238 patients with lung adenocarcinoma were investigated.
      Quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR)
      assays were performed to evaluate the gene expression of IGF1R, and
      immunohistochemical staining was done to evaluate the protein expression of
      IGF1R. RESULTS: Among the 238 patients with lung adenocarcinoma, 107 tumors
      (45.0%) were IGF1R-low and 131 tumors (55.0%) were IGF1R-high. The IGF1R gene
      expression ratio was significantly lower in moderately to poorly differentiated
      adenocarcinomas than in well-differentiated adenocarcinomas (P = 0.0388). Gene
      expression of IGF1R was significantly correlated with protein expression of IGF1R
      (r = 0.7163, P < 0.0001). Regarding patient survival, overall survival was
      significantly lower in patients with IGF1R-low tumors than in those with IGF1R
      high tumors (63.2% versus 76.1% 5-year survival, P = 0.0188). Multivariate
      analysis using a Cox proportional-hazards model demonstrated that IGF1R gene
      status was a significant prognostic factor predicting overall survival of
      patients with lung adenocarcinoma (hazard ratio 1.800; P = 0.0321). Moreover, the
      disease-free survival rate was significantly lower in patients with IGF1R-low
      tumors than in those with IGF1R-high tumors (49.2% versus 64.6% 5-year survival,
      P = 0.0084). CONCLUSION: The present study suggests the level of IGF1R expression
      to be a useful prognostic marker for patients with dedifferentiated lung
      adenocarcinoma.

PMID- 21732142
TI  - A risk model for secondary cytoreductive surgery in recurrent ovarian cancer: an
      evidence-based proposal for patient selection.
AB  - BACKGROUND: To develop a risk model for predicting complete secondary
      cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. METHODS:
      Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR
      from 7 worldwide centers were pooled and analyzed. The risk model was developed
      based on the factors impacting on SCR surgical outcome. Additional data on 117
      patients who were not included in the development of the model were used for
      external validation and to assess the discrimination of the model. RESULTS: Of
      the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary
      cytoreduction was associated with six variables: FIGO stage (odds ratio [OR] =
      1.32, 95% confidence interval [95% CI]: 0.97-1.80), residual disease after
      primary cytoreduction (OR = 1.69, 95% CI: 1.26-2.27), progression-free interval
      (OR = 2.27, 95% CI: 1.71-3.01), Eastern Cooperative Oncology Group (ECOG)
      performance status (OR = 2.23, 95% CI: 1.45-3.44), CA125 (OR = 1.85, 95% CI: 1.41
      2.44), and ascites at recurrence (OR = 2.79, 95% CI: 1.88-4.13). These variables
      were entered into the risk model and assigned scores ranging from 0 to 11.9.
      Patients with total scores of 0-4.7 were categorized as the low-risk group, in
      which the proportion of complete cytoreduction was 53.4% compared with 20.1% in
      the high-risk group (OR = 4.55, 95% CI: 3.43-6.04). In external validation, the
      sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the
      curve of the receiver-operating characteristics for predicting complete SCR was
      0.68 (95% CI: 0.60-0.79). CONCLUSIONS: This model and scoring system may well
      predict the outcome of SCR and could potentially be useful in future clinical
      trials to determine which patients with recurrent ovarian cancer should have SCR
      as part of their management.

PMID- 21732143
TI  - Twist1 is an independent prognostic factor of esophageal squamous cell carcinoma
      and associated with its epithelial-mesenchymal transition.
AB  - BACKGROUND: Twist1 is known to be involved in epithelial-mesenchymal transition
      (EMT) and tumor progression. However, its specific role is different depending on
      the type of cancer. The functional role and clinical significance of Twist1 in
      esophageal squamous cell carcinoma (ESCC) have been rarely studied. METHODS: We
      examined Twist1 expression in a total of 199 samples using immunohistochemistry
      and real-time reverse-transcription polymerase chain reaction (RT-PCR). We also
      studied the association of Twist1 with EMT of ESCC using tissue samples and in
      vitro models. In addition, we examined the changes in the whole-genome expression
      profiles of two ESCC cell lines after inducing upregulation of Twist1. RESULTS:
      Twist1 expression was increased in ESCC compared with that of normal esophagus (P
      < 0.01). We found that expression of Twist1 was strongly associated with poor
      prognosis on both univariate analysis [relative risk (RR) = 3.019, P = 0.000] and
      multivariate analysis (RR = 3.131, P = 0.000). In addition, we found that Twist1
      expression was strongly correlated with EMT in ESCC tissues. Upregulation of
      Twist1 induced other EMT inducers in all three esophageal cancer cell lines
      investigated (TE1, TE8, and TE10). Twist1 also enhanced the migratory and
      invasive abilities of all three cell lines. Finally, microarray analysis of gene
      expression in the three ESCC cell lines revealed that Twist1 upregulation
      affected the expression of mainly cytoskeleton and extracellular matrix-related
      genes, which are directly related to cell morphology and movement. CONCLUSIONS:
      Our study indicates that Twist1 is associated with EMT of esophageal squamous
      cell carcinoma and may be used as a diagnostic and prognostic biomarker in ESCC.

PMID- 21732144
TI  - Eucalcemic parathyroid hormone elevation after parathyroidectomy for primary
      sporadic hyperparathyroidism: risk factors, trend, and outcome.
AB  - BACKGROUND: Patients with eucalcemic parathyroid hormone elevation (ePTH) after
      parathyroidectomy for primary hyperparathyroidism (HPT) may be at risk of
      recurrence. We aimed to examine risk factors, trend of PTH level, and outcome of
      patients with ePTH 6 months after parathyroidectomy. METHODS: A total of 161
      primary HPT were analyzed. The 6-month postoperative calcium and PTH levels were
      obtained. ePTH was defined as an elevated PTH level in the presence of
      normocalcemia. At 6 months, 98 had eucalcemic normal PTH and 63 (39.1%) had ePTH.
      Perioperative variables, PTH trend, and outcome were compared between 2 groups.
      Multivariable analyses were performed to identify independent preoperative and
      operative/postoperative risk factors for ePTH. RESULTS: Among preoperative
      factors, advanced age (odds ratio [OR] = 1.042, P = .027) and low 25
      hydroxyvitamin D(3) (25OHD(3)) (OR = 1.043, P = .009) were independently
      associated with ePTH, whereas among operative/postoperative factors, high 10-min
      intraoperative PTH level (OR = 1.015, P = .040) and high postoperative 3-month
      PTH (OR = 1.048, P < .001) were independently associated with ePTH. After a mean
      follow-up of 38.7 months, recurrence rate was similar between the 2 groups (P =
      1.00). In the first 2 postoperative years, 75 (46.6%) had ePTH on at least 1
      occasion and 8 (5.0%) had persistently ePTH on every occasion. CONCLUSIONS:
      Advanced age, low 25OHD(3), high 10-min intraoperative PTH, and high
      postoperative 3-month PTH were independently associated with ePTH at 6-month.
      Although 39.1% of patients had ePTH at 6 months, more than 50% had at least 1
      ePTH within the first 2 years of follow-up. Recurrence appeared similar between
      those with or without ePTH at 6 months.

PMID- 21732145
TI  - Hepatic resection for "BCLC stage A" hepatocellular carcinoma. The prognostic
      role of alpha-fetoprotein.
AB  - BACKGROUND: Our aim was to assess the capability of Barcelona Clinic Liver Cancer
      (BCLC) staging system in allocating stage A patients to hepatic resection (HR)
      and the effect on survival. METHODS: We enrolled 132 patients with hepatocellular
      carcinoma (HCC) amenable to HR. All patients underwent ultrasound (US)-guided
      anatomical resection (<=2 segments) and then postoperative results were
      evaluated. RESULTS: Results showed 95% of patients were Child A, 49% in BCLC A1,
      21% in A2, 6% in A3, and 24% in A4. No 30-day mortality occurred. Overall
      survival got worse from A1 to A4 (P = 0.0271), while no differences were found in
      Childs A patients with or without portal hypertension (P = 0.1674). Multivariate
      analysis (Cox model) shows that only AFP (<20 ng/ml) was an independent predictor
      of survival: If the AFP is incorporated in BCLC staging system (all A1 and A2
      patients with abnormal AFP levels were included in A3 subgroup), 5-year survival
      rate including normal AFP for A1 was 57% and for A2 was 65%, whereas the survival
      rates impaired in the worst candidates (5-year survival rate including AFP
      abnormal for A3 and A4 was 36%; P = 0.002). So, introducing AFP in BCLC
      classification it is possible to simplify the algorithm in only 2 classes, well
      separated in survival curves (class 1 [AFP-]: 60%; class 2 [AFP+]: 37%; P =
      0.0001). CONCLUSION: Our experience stressed the high value of BCLC system in
      staging of patients with HCC, but underlined that in selected patients (normal
      AFP) even A2 group may benefit from HR with a good survival.

PMID- 21732146
TI  - [Treatment of gunpowder tattoo and foreign bodies after blast injuries].
AB  - Gunpowder traumatic tattoo and foreign bodies in the skin secondary to explosions
      or gunshots need to be treated within 72 h if possible to achieve good aesthetic
      results. Hypertrophic scars can be treated by skin resurfacing using the Erb-YAG
      laser or the CO2 laser, while traumatic tattoos can be removed with the Q
      switched rubin laser.

PMID- 21732147
TI  - [Computer-assisted reconstruction of the facial skeleton].
AB  - Injury to the facial skeleton may result not only in aesthetic but also
      functional deficits. Computer-assisted surgery promises predictable
      reconstructive results. In clinical routine the authors use the combination of
      preoperative planning, intraoperative navigation and intraoperative imaging to
      treat complex facial trauma. With preoperative planning the intended
      reconstructive results can be precisely preplanned and guided intraoperatively
      using navigational surgery. Intraoperative imaging achieves the final
      intraoperative validation. Using computer-assisted surgery dislocation and
      malformation of fragments and transplants can be avoided in facial
      reconstruction. This means reliable quality control of surgical outcome and the
      number of further surgeries can be reduced in this complex reconstructive
      surgery.

PMID- 21732149
TI  - [Correlation of pure tone thresholds and hearing loss for numbers. Comparison of
      three calculation variations for plausibility checking in expertise].
AB  - BACKGROUND: The present study analyzes the best combination of frequencies for
      the calculation of mean hearing loss in pure tone threshold audiometry for
      correlation with hearing loss for numbers in speech audiometry, since the
      literature describes different calculation variations for plausibility checking
      in expertise. Three calculation variations, A (250, 500 and 1000 Hz), B (500 and
      1000 Hz) and C (500, 1000 and 2000 Hz), were compared. METHODS: Audiograms in 80
      patients with normal hearing, 106 patients with hearing loss and 135 expertise
      patients were analyzed in a retrospective manner. Differences between mean pure
      tone audiometry thresholds and hearing loss for numbers were calculated and
      statistically compared separately for the right and the left ear in the three
      patient collectives. RESULTS: We found the calculation variation A to be the best
      combination of frequencies, since it yielded the smallest standard deviations
      while being statistically different to calculation variations B and C. The 1- and
      2.58-fold standard deviation (representing 68.3% and 99.0% of all values) was +/
      4.6 and +/-11.8 dB for calculation variation A in patients with hearing loss,
      respectively. CONCLUSIONS: For plausibility checking in expertise, the mean
      threshold from the frequencies 250, 500 and 1000 Hz should be compared to the
      hearing loss for numbers. The common recommendation reported by the literature to
      doubt plausibility when the difference of these values exceeds +/-5 dB is too
      strict as shown by this study.

PMID- 21732150
TI  - [Recurrent epistaxis of unknown origin. A rare differential diagnosis and its
      treatment].
AB  - We present the case report on a 66-year-old male patient who appeared in our
      clinic with recurrent epistaxis. Anterior rhinoscopy during acute bleeding
      yielded no information on the origin of hemorrhage. On renewed epistaxis,
      angiography was performed on which an arteriovenous malformation in the sphenoid
      sinus could be identified as the cause of epistaxis. Embolization of afferent
      vessels successfully reduced the malformation and stopped the bleeding. In cases
      of recurrent epistaxis, especially in combination with an unremarkable anterior
      rhinoscopy, angiography is recommended for the detection of life-threatening
      vessel malformations.

PMID- 21732148
TI  - [Penetrating injuries in the face and neck region. Diagnosis and treatment].
AB  - Penetrating head and neck injuries often present with vascular lesions and airway
      compromise and may be life-threatening. Thus controlling bleeding and airway
      stabilisation take priority in emergency treatment. High-velocity projectiles,
      fragmentations from improvised explosive devices (IEDs) and shrapnel can cause
      severe tissue injury, representing a challenge for the head and neck surgeon.
      Since several organ structures, such as the eyes, midface, pharynx, larynx,
      trachea, esophagus, nerves, vessels and vertebral spine can be injured at the
      same time, patients should be referred to a specialized trauma center for
      interdisciplinary treatment following emergency treatment. High-speed ballistic
      injuries were once confined to the battle field and have been uncommon in Europe
      since World War II. For this reason, experience among civilian head and neck
      surgeons is at present limited. With the increased incidence of terrorism and the
      use of IEDs as the preferred weapon in terrorism it has become important for
      civilian head and neck surgeons to understand the role of ballistic injuries in
      mass casualty events. The present paper discusses current viewpoints in the
      diagnosis and treatment of penetrating head and neck injuries.

PMID- 21732151
TI  - [Bilateral deafness due to labyrinthitis in a patient with Crohn's disease].
AB  - Labyrinthitis with vestibulocochlear dysfunction in chronic inflammatory bowl
      disease is a rare but well described manifestation or complication. The
      diagnostic and therapeutic possibilities and limitations of this inflammatory
      otopathy are presented and discussed in the context of a case report. A bilateral
      loss of vestibular function and sensorineural hearing loss occurred in a 26-year
      old male patient with previously diagnosed Crohn's disease. He was treated with
      immune suppressive therapy during the onset and development of cochleovestibular
      symptoms. Diagnostic tests included pure tone audiograms, speech audiometry,
      caloric tests, VEMPs, and MRI. Therapy included azathioprine, corticosteroids
      (systemic and intratympanic), monoclonal antibodies, and cochlear implants.
      Despite immunosuppressive therapy including monoclonal antibodies, the patient
      progressively lost his hearing. Finally, bilateral cochlear implantation was
      carried out with good results. The treatment of patients with systemic
      inflammatory or autoimmune disease affecting the cochlear-vestibular organ is
      challenging. An interdisciplinary approach is needed. In cases of bilateral
      deafness, cochlear implantation is a satisfactory treatment and should not be
      delayed unnecessarily.

PMID- 21732152
TI  - Solid lipid nanoparticles loaded with anti-microRNA oligonucleotides (AMOs) for
      suppression of microRNA-21 functions in human lung cancer cells.
AB  - PURPOSE: Literature has highlighted the practical use of solid lipid
      nanoparticles (SLNs) in research, but few reports have combined SLNs with miRNA
      based therapy. We aimed to prepare SLNs to load anti-miRNA oligonucleotide (AMO)
      for miRNA-based therapy in vitro. METHODS: SLNs were employed to encapsulate AMO
      by a solvent diffusion method, and then the properties of AMO-CLOSs (cationic
      lipid binded oligonucleotide (AMO)-loaded SLNs) were characterized. We studied
      cellular uptake and activation properties of AMO-CLOSs in A549 cells, including
      antisense efficiency, cell migration and invasion. RESULTS: AMO-CLOSs were 187 nm
      in size and 46.6 mV in zeta potential with an approximately toroid morphology in
      the TEM image. AMO-CLOSs uptake by A549 cells was increased significantly higher
      and more effective than free AMO. Further results demonstrated that AMO-CLOSs
      showed high antisense efficiency of microRNA-21 and subsequently decreased the
      proliferation, migration and invasion of tumor cells. CONCLUSIONS: These findings
      suggest that AMO-CLOSs represent a potential new approach for carrying anti-miRNA
      inhibitors for cancer therapy.

PMID- 21732154
TI  - Candida esophagitis as the cause of swallowing disturbances in an 85-year-old
      patient with myasthenia gravis.
AB  - An 85-year-old man with myasthenia gravis was successfully treated with
      methotrexate (10 mg/week), pyridostigmine and prednisolone (0-30 mg/day) for over
      10 years. Then, he developed dysphagia and lost weight. Gastroscopy revealed
      Candida esophagitis. The patient received nystatin for 2 weeks. Methotrexate was
      stopped, and immunosuppressive therapy was continued with prednisolone alone. The
      patient has now remained in good condition for over 1 year. Although dysphagia is
      a typical symptom of myasthenia gravis, swallowing disturbances should not be
      attributed hastily to this disease, since they may also be a complication of
      therapy.

PMID- 21732153
TI  - An acetate prodrug of a pyridinol-based vitamin E analogue.
AB  - PURPOSE: To investigate of an approach to stabilize a novel pyridinol based alpha
      tocopherol analogue (1) as a prodrug by acetylation of its phenol moiety.
      METHODS: Biochemical indicators of oxidative stress in mitochondria were utilized
      to gain insight into the cytoprotective mechanism(s) of compound 1 acetate.
      Oxygen free radical scavenging activity was measured using DCF probe in a
      cultured cell model system that had been placed under oxidative stress. Lipid
      peroxidation was examined both in a cell-free system and in oxidatively stressed
      cultured cells. The bioenergetic parameters of mitochondria were evaluated by
      measuring mitochondrial membrane potential (Deltapsi(m)) and the MPT. RESULTS:
      The present results suggest strongly that the antioxidant efficacy of compound 1
      can be improved by using it as a prodrug. The tested prodrug has shown to be
      activated as a function of time, presumably due to susceptibility to enzymatic
      hydrolysis, and exhibits an antioxidant effect in time-dependent manner,
      providing a compound that is more effective than alpha-tocopherol acetate with
      regard to all protective properties studied. CONCLUSIONS: An effective approach
      to stabilize compound 1 was realized by using its acetate as a prodrug.

PMID- 21732155
TI  - [Outcome and predictors of early geriatric rehabilitation in an acute care
      setting].
AB  - BACKGROUND: Geriatric assessment and treatment including an interdisciplinary
      team is a well accepted method to improve functionality and mortality in the
      elderly. Nevertheless, only little evidence and limited data are available
      concerning the outcome of this approach in an acute care setting and early
      rehabilitation. PATIENTS AND METHODS: All patients included in a comprehensive
      geriatric program within 1 year were eligible for inclusion in a retrospective
      chart analysis. Admission to the program was allowed after counseling by an
      experienced geriatrician applying pre-defined criteria including significant
      deconditioning, preserved rehabilitation prognosis and/or ongoing instable
      medical condition requiring an acute care setting. Patients who refused therapy
      or died within the first week of treatment were excluded. A telephone interview
      was performed 6 months after patient discharge and data concerning mortality,
      functional course and quality of life (activities of daily life ADL) were
      retrieved. All patients were treated in an acute care setting in two geriatric
      and general internal medicine wards. RESULTS: A total of 138 patients were
      included in the program. In 128 cases data concerning the 6 month mortality could
      be retrieved and 92 patients agreed to participate in a complete telephone
      interview. Mortality within the early rehabilitation course was 4%, the 6 month
      mortality however was 28%. Functionality improved during early rehabilitation and
      a median increment of 10 points in the Barthel index was found (range 0-100).
      Analysis of individual increments showed high interindividual variability
      throughout the whole range of the ADL score at the beginning of the treatment.
      Concerning the 6 month course after hospital discharge functionality remained at
      a steady median value but showed a large range of both increasing and decreasing
      ADL values. Analysis of predictors by logistic regression revealed the ADL score
      on admission to the early rehabilitation program as the predominant predictor
      overriding other factors such as depression or cognitive impairment. An ADL value
      <=15 on admission was a strong predictor for an unfavorable outcome in early
      rehabilitation defined as death or an ADL increment <=10. An ADL value <=15 on
      admission was also a strong predictor for overall mortality within 6 months. On
      the other hand an ADL value <=15 on admission was a strong predictor for a steady
      or increasing functionality among the survivors of the 6 month postdischarge
      interval. CONCLUSIONS: The mortality rate in the early rehabilitation course in
      this preliminary and observational study was relatively low and may be explained
      by both the exclusion of patients not surviving the first week of treatment and
      an effective inclusion algorithm. The high overall 6 month mortality rate may
      also be explained by the selection of patients focusing on those severely
      functionally impaired. This subpopulation of elderly inpatients in acute care
      units reveals a high vulnerability to critical incidents. Besides scale effects
      there is also a remarkable variability in the 6 month postdischarge course
      pointing to heterogeneity and different patterns concerning the time course of
      functionality.

PMID- 21732156
TI  - Successful treatment of recurrent basilar artery occlusion with intra-arterial
      thrombolysis and vertebral artery coiling in a child.
AB  - BACKGROUND: Signs of brainstem ischemia in children may be subtle, and outcome
      following basilar artery occlusion is often poor. There currently are no
      guidelines in children regarding the best methods to diagnose and treat basilar
      artery occlusion. METHODS: Case report and literature review. RESULTS: We
      describe the presentation and management of recurrent basilar artery occlusion in
      a previously healthy 5-year-old boy with vertebral artery dissection. Treatment
      included emergent intra-arterial tPA and mechanical thrombolysis of basilar
      artery clot, followed by later coiling of the vertebral artery to prevent
      recurring episodes of basilar artery ischemia. CONCLUSION: Management of
      brainstem stroke in children requires coordination of neurology, critical care,
      and interventional radiology services. Delayed intra-arterial thrombolysis and
      vertebral artery coiling can be successfully used to treat basilar artery
      occlusion and prevent the recurrence of brainstem ischemia in children.

PMID- 21732157
TI  - Solution-mediated phase transformation of haloperidol mesylate in the presence of
      sodium lauryl sulfate.
AB  - Forming a salt is a common way to increase the solubility of a poorly soluble
      compound. However, the solubility enhancement gained by salt formation may be
      lost due to solution-mediated phase transformation (SMPT) during dissolution. The
      SMPT of a salt can occur due to a supersaturated solution near the dissolving
      surface caused by pH or other solution conditions. In addition to changes in pH,
      surfactants are also known to affect SMPT. In this study, SMPT of a highly
      soluble salt, haloperidol mesylate, at pH 7 in the presence of a commonly used
      surfactant, sodium lauryl sulfate (SLS), was investigated. Dissolution
      experiments were performed using a flow-through dissolution apparatus with
      solutions containing various concentrations of SLS. Compacts of haloperidol
      mesylate were observed during dissolution in the flow-through apparatus using a
      stereomicroscope. Raman microscopy was used to characterize solids. The
      dissolution of haloperidol mesylate was significantly influenced by the addition
      of sodium lauryl sulfate. In conditions where SMPT was expected, the addition of
      SLS at low concentrations (0.1-0.2 mM) reduced the dissolution of haloperidol
      mesylate. In solutions containing concentrations of SLS above the critical
      micelle concentration (CMC) (10-15 mM), the dissolution of haloperidol mesylate
      increased compared to below the CMC. The solids recovered from solubility
      experiments of haloperidol mesylate indicated that haloperidol free base
      precipitated at all concentrations of SLS. Above 5 mM of SLS, Raman microscopy
      suggested a new form, perhaps the estolate salt. The addition of surfactant in
      solids that undergo solution-mediated phase transformation can add complexity to
      the dissolution profiles and conversion.

PMID- 21732158
TI  - Macrophage-specific targeting of isoniazid through mannosylated gelatin
      microspheres.
AB  - Active targeting of drug molecules can be achieved by effective attachment of
      suitable ligands to the surface of carriers. The present work was attempted to
      prepare mannosylated gelatin microspheres (m-GMs) so as to achieve targeted
      delivery of isoniazid (INH) to alveolar macrophages (AMs) and maintain its
      therapeutic concentration for prolonged period of time. Microspheres were
      prepared by emulsification solvent extraction method and evaluated for
      physicochemical characteristics, drug release, ex vivo drug uptake by AMs and
      pharmacokinetic characteristics. Fourier transform infrared spectroscopy and
      nuclear magnetic resonance spectral analysis confirmed that mannosylation took
      place through Schiff base formation between aldehyde and amino groups of mannose
      and gelatin, respectively. Prepared microspheres offered suitable physicochemical
      characteristics for their delivery to AMs. Their average size was about 4 MUm and
      drug entrapment efficiency of 56% was achieved with them. Ex vivo uptake results
      indicated that in comparison to plain microspheres, m-GMs were selectively
      uptaken and were found to be associated with phago-lysosomal vesicles of AMs.
      Pharmacokinetic studies showed the formulation could maintain the therapeutic
      concentration of INH for prolonged period of time even with a reduced clinical
      dose. m-GMs were found to be stable in broncheo-alveolar lavage fluid. The study
      concluded that ligand decorated carriers could be a potential strategy to improve
      the therapeutic properties of INH.

PMID- 21732159
TI  - Platelet lysate mucohadesive formulation to treat oral mucositis in graft versus
      host disease patients: a new therapeutic approach.
AB  - Optimal treatment of oral mucositis (OM) due to graft versus host disease (GvHD)
      is currently not available. Platelet-derived growth factors (PDGFs) have high
      capability for tissue healing and may play a role in repairing the mucosal
      barrier. The aim of the present work was to develop a mucoadhesive formulation to
      administer platelet lysate to oral cavity prolonging contact time of platelet
      lysate with oral mucosa. The mucoadhesive formulation was characterized for in
      vitro properties (PDGF-AB concentration, mucoadhesive properties, cytotoxicity,
      fibroblast proliferation, wound healing). Moreover, a preliminary clinical study
      on seven GvHD patients with OM refractory to other therapies was conducted, to
      evaluate feasibility, safety, and efficacy. GVPL (mucoadhesive gel vehicle mixed
      with platelet lysate)showed good mucoadhesive properties; additionally, it was
      characterized by good biocompatibility in vitro on fibroblasts and it was able to
      enhance fibroblast proliferation and wound healing, maintaining the efficacy for
      up to 14 days following storage at 2-8 degrees C. In vivo, clinical response was
      good-to-complete in five, fair in one, none in the remaining one. The in vitro
      results indicate that GVPL has optimal mucoadhesive and healing enhancer
      properties, maintained over time (up to 14 days); preliminary clinical results
      suggest that oral application of platelet lysate-loaded mucoadhesive formulation
      is feasible, safe, well tolerated, and effective. A larger controlled randomized
      study is needed.

PMID- 21732160
TI  - [Acquired reactive perforating collagenosis following herpes zoster as isotopic
      response?].
AB  - Reactive perforating collagenosis is a disease whose pathogenesis is still not
      fully understood. Histological findings are degenerated collagen bundles which
      are arranged in vertical direction penetrating the epidermis into a dome-shaped
      crater. Usually diabetes mellitus and renal failure can be found among patients
      with reactive perforating collagenosis. To date, there have been five cases
      described where the eruption of reactive perforating collagenosis followed herpes
      zoster infection. This could be a form of Wolf's isotopic response, a term that
      is used for dermatoses which arise after the healing of a preexisting dermatosis.
      We report the sixth case of a herpes zoster-associated reactive perforating
      collagenosis and discuss the current literature.

PMID- 21732161
TI  - [Beauty from the inside. Does it really work?].
AB  - Skin functions and healthy appearance depend on a sufficient supply of essential
      nutrients. The relationship between nutrition and skin has become a hot topic
      that is exciting researchers and clinicians worldwide. Intervention studies
      indicate that it is in fact possible to manipulate and to delay skin aging and to
      improve skin conditions through supplementation with selected nutritional
      supplements. It has been shown that diet-based anti-aging strategies are most
      effective when directed against extrinsic skin aging. New insights into the
      effects of orally-administered, biologically active molecules on skin functions
      have stimulated a continuously growing interest in the development of nutritional
      supplements and functional food products to benefit human skin. This article
      attempts to provide a briefly overview to some of the healthy and protective
      substances used as functional food.

PMID- 21732162
TI  - [Immunosenescence. Current status and molecular mechanisms].
AB  - One of the most important biological changes occurring during human aging is
      termed 'immunosenescence' characterized by a functional decline in immunity
      leading to a progressive immunodeficiency. Regulatory mechanisms also are
      diminished, leading to an inefficient and poorly controlled pro-inflammatory
      activation of the immune response. This increases the risk for disorders such as
      infectious, autoimmune, neoplastic, cardiovascular and neurodegenerative disease.
      Many of these entities are quite relevant for dermatology. Hence,
      immunosenescence constitutes a pathologic process contributing to morbidity and
      mortality of important clinical relevance in an aging population. Investigation
      of the underlying pathomechanisms and the application of modern mechanism
      directed therapy offer many opportunities for a targeted modulation and
      "rejuvenation", thus indicating possible targets for the reduction of age
      associated morbidity and mortality. Some promising targeted 'molecular' therapies
      are already currently being used in the context of other diseases, also in the
      field of dermatology.

PMID- 21732163
TI  - [Necrobiosis lipoidica. Variants on a theme].
AB  - A 69-year-old patient presented with different skin lesions all of which belonged
      to group of necrobiosis lipoidica. The initial histologic diagnosis was actinic
      granuloma O'Brien. A subsequent biopsy was interpreted as granulomatous
      necrobiosis lipoidica. The history of these necrobiotic variants is reviewed and
      exemplarily depicted with this case. Necrobiosis lipoidica is part of the
      spectrum of granulomatous skin disorders. Although its etiology is unclear, an
      association with diabetes mellitus is often discussed. Multiple therapeutic
      options exist, but standardized guidelines for treatment are missing.

PMID- 21732164
TI  - Microvessel density but not neoangiogenesis is associated with 18F-FDG uptake in
      human atherosclerotic carotid plaques.
AB  - INTRODUCTION: The vulnerable atherosclerotic lesion exhibits the proliferation of
      neovessels and inflammation. The imaging modality 2-deoxy-2-[(18)F]fluoro-D: 
      glucose positron emission tomography ((18)FDG-PET) is considered for the
      identification of vulnerable plaques. PURPOSE: The purpose of this study was to
      compare the gene expression of neoangiogenesis and vulnerability-associated genes
      with (18)FDG uptake in patients undergoing carotid endarterectomy. PROCEDURES:
      Human atherosclerotic carotid artery plaques from symptomatic patients were used
      for gene expression analysis by quantitative PCR of vascular endothelial growth
      factor (VEGF) and integrin alpha(V) and integrin beta(3) subunits, genes
      essential during neoangiogenesis. We also evaluated the gene expression of CD34,
      a measure of microvessel density (MVD), as well as CD68, MMP-9, and cathepsin K,
      genes of major importance in plaque vulnerability. Gene expression analysis was
      compared with (18)FDG-PET. RESULTS: VEGF and integrin alpha(V)beta(3) gene
      expression did not correlate with (18)FDG uptake, whereas CD34 gene expression
      exhibited an inverse correlation with (18)FDG uptake. Additionally, we
      established that markers of vulnerability were correlated with (18)FDG uptake.
      CONCLUSIONS: Neoangiogenesis is not associated with (18)FDG uptake, whereas MVD
      and markers of vulnerability correlate with (18)FDG uptake. The absence of
      correlation between markers of neoangiogenesis and (18)FDG uptake suggests a
      temporal separation between the process of neoangiogenesis and inflammatory
      activity.

PMID- 21732165
TI  - Preclinical evaluation of radiolabeled DOTA-derivatized cyclic minigastrin
      analogs for targeting cholecystokinin receptor expressing malignancies.
AB  - PURPOSE: Targeting of cholecystokinin receptor expressing malignancies such as
      medullary thyroid carcinoma is currently limited by low in vivo stability of
      radioligands. To increase the stability, we have developed and preclinically
      evaluated two cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      (DOTA)-minigastrin analogs radiolabeled with (111)In and (68)Ga. PROCEDURES:
      Radiolabeling efficiency, in vitro characterization, cholecystokinin receptor
      subtype 2 (CCK-2) binding in human tumor tissues, and cell internalization on CCK
      2 receptor expressing AR42J cells, as well as biodistribution and small animal
      imaging in two different mouse xenograft models were studied. RESULTS: High
      receptor affinity and receptor-mediated uptake of the radioligands in AR42J cells
      was confirmed in vitro. (111)In-labeled cyclic DOTA-peptides showed a specific
      tumor uptake of ~1% ID/g in vivo, (68)Ga-labeled analogs of ~3% ID/g. Small
      animal SPECT imaging resulted to be superior with (111)In-DOTA-cyclo-MG2 in
      comparison with (111)In-DOTA-cyclo-MG1. CONCLUSIONS: Cyclic DOTA-minigastrin
      analogs are promising candidates for gastrin receptor scintigraphy and targeted
      radionuclide therapy.

PMID- 21732166
TI  - Gender and use of hypnotics or sedatives in old age: a nationwide register-based
      study.
AB  - OBJECTIVE: To investigate whether gender is associated with use of hypnotics or
      sedatives and with different types of hypnotics or sedatives in older people
      after adjustment for age, socioeconomic status (i.e., education) and co-morbidity
      (i.e., number of other drugs). SETTING: Sweden Method We conducted a register
      based analysis of data on gender, age, dispensed drugs, and education from people
      aged 75-89 years registered in the Swedish Prescribed Drug Register between July
      and October 2005 (n = 645,429). MAIN OUTCOME MEASURE: The hypnotic or sedative
      drug classes were benzodiazepines, benzodiazepine related drugs (i.e., Z-drugs)
      and other types of hypnotics or sedatives. The individual hypnotics or sedatives
      were nitrazepam, flunitrazepam, triazolam, zopiclone, zolpidem, clomethiazole and
      propiomazine. RESULTS: In the total study population, 27.1% of the women and
      18.1% of the men were dispensed at least one hypnotic or sedative drug. The
      logistic regression analyses of those who used hypnotics or sedatives (n =
      151,700) revealed that women were more likely than men to use benzodiazepines
      (adjusted OR = 1.11; 95% CI 1.07-1.14) and benzodiazepine related drugs (adjusted
      OR = 1.14; 95% CI 1.12-1.17), whereas men were more likely to use other types of
      hypnotics or sedatives (adjusted OR = 0.69; 95% CI 0.67-0.71). Among the
      individual hypnotics or sedatives, the strongest associations with gender was
      found for nitrazepam (adjusted OR = 1.19; 95% CI 1.14-1.25 for women compared
      with men), zolpidem (adjusted OR = 1.18; 95% CI 1.16-1.21), clomethiazole
      (adjusted OR = 0.48; 95% CI 0.46-0.51) and propiomazine (adjusted OR = 0.77; 95%
      CI 0.75-0.79). CONCLUSION: Use of hypnotics or sedatives in old age seems to be
      related to female gender. Also, among elderly users of hypnotics or sedatives,
      women appear to be more likely to use benzodiazepines and benzodiazepine related
      drugs than men. The explanation to these gender differences merits further
      investigation.

PMID- 21732167
TI  - The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic:
      preparation for severe respiratory emergency outbreaks.
AB  - PURPOSE: In view of the expected 2009 influenza A(H1N1) pandemic, the Italian
      Health Authorities set up a national referral network of selected intensive care
      units (ICU) able to provide advanced respiratory care up to extracorporeal
      membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome
      (ARDS). We describe the organization and results of the network, known as
      ECMOnet. METHODS: The network consisted of 14 ICUs with ECMO capability and a
      national call center. The network was set up to centralize all severe patients to
      the ECMOnet centers assuring safe transfer. An ad hoc committee defined criteria
      for both patient transfer and ECMO institutions. RESULTS: Between August 2009 and
      March 2010, 153 critically ill patients (53% referred from other hospitals) were
      admitted to the ECMOnet ICU with suspected H1N1. Sixty patients (48 of the
      referred patients, 49 with confirmed H1N1 diagnosis) received ECMO according to
      ECMOnet criteria. All referred patients were successfully transferred to the
      ECMOnet centers; 28 were transferred while on ECMO. Survival to hospital
      discharge in patients receiving ECMO was 68%. Survival of patients receiving ECMO
      within 7 days from the onset of mechanical ventilation was 77%. The length of
      mechanical ventilation prior to ECMO was an independent predictor of mortality.
      CONCLUSIONS: A network organization based on preemptive patient centralization
      allowed a high survival rate and provided effective and safe referral of patients
      with severe H1N1-suspected ARDS.

PMID- 21732168
TI  - Epidemiology and outcome following post-surgical admission to critical care.
AB  - PURPOSE: To describe the factors related to outcome in patients admitted to the
      intensive care unit (ICU) after major surgery at a national level (in Austria).
      METHODS: Analysis of a prospectively collected database of ICU admissions over an
      11-year period. Factors associated with mortality and how this changed with time
      were explored using logistic multilevel modelling. RESULTS: A total of 88,504
      surgical patients had a mean ICU length of stay of 6.5 days and total hospital
      stay of 31.3 days. They had an ICU mortality of 7.6% and a hospital mortality of
      11.8%. Factors associated with hospital mortality included age (odds ratio (OR)
      1.42 per 10 years of age), urgency of operation (2.02 for emergency when compared
      to elective), SAPS II score (OR 1.09), reason for admission being a medical cause
      and the specific nature of the surgery itself: thoracic (OR 1.81), cardiovascular
      (OR 1.25), trauma (OR 1.22) or gastrointestinal surgery (OR 1.71). In addition
      patients who had pre-existing chronic renal (OR 1.40), respiratory (OR 1.20) or
      cardiac failure (OR 1.29), cirrhosis (OR 2.50), alcoholism (OR 1.42), acute
      kidney injury (OR 1.88) and/or non-metastatic cancer (OR 1.20) were associated
      with higher hospital mortality than patients without this co-morbidity. There was
      a reduction in the OR for death over the whole 11-year period. This improved
      outcome remained valid even after adjusting for the identified risk factors for
      mortality (OR per year 0.96). CONCLUSIONS: This study has shown the high level of
      demand for critical care for this patient group and an improving rate of
      survival.

PMID- 21732169
TI  - The relationship history calendar: improving the scope and quality of data on
      youth sexual behavior.
AB  - Most survey data on sexual activities are obtained via face-to-face interviews,
      which are prone to misreporting of socially unacceptable behaviors. Demographers
      have developed various private response methods to minimize social desirability
      bias and improve the quality of reporting; however, these methods often limit the
      complexity of information collected. We designed a life history calendar-the
      Relationship History Calendar (RHC)-to increase the scope of data collected on
      sexual relationships and behavior while enhancing their quality. The RHC records
      detailed, 10-year retrospective information on sexual relationship histories. The
      structure and interview procedure draw on qualitative techniques, which could
      reduce social desirability bias. We compare the quality of data collected with
      the RHC with a standard face-to-face survey instrument through a field experiment
      conducted among 1,275 youth in Kisumu, Kenya. The results suggest that the RHC
      reduces social desirability bias and improves reporting on multiple measures,
      including higher rates of abstinence among males and multiple recent sexual
      partnerships among females. The RHC fosters higher levels of rapport and
      respondent enjoyment, which appear to be the mechanisms through which social
      desirability bias is minimized. The RHC is an excellent alternative to private
      response methods and could potentially be adapted for large-scale surveys.

PMID- 21732170
TI  - Education and male-female differences in later-life cognition: international
      evidence from Latin America and the Caribbean.
AB  - This study explores the role of early-life education for differences in cognitive
      functioning between men and women aged 60 and older from seven major urban areas
      in Latin America and the Caribbean. After documenting statistically significant
      differences in cognitive functioning between men and women for six of the seven
      study sites, I assess the extent to which these differences can be explained by
      prevailing male-female differences in education. I decompose predicted male
      female differences in cognitive functioning based on various statistical models
      for later-life cognition and find robust evidence that male-female differences in
      education are a major driving force behind cognitive functioning differences
      between older men and women. This study therefore suggests that early-life
      differences in educational attainment between boys and girls during childhood
      have a lasting impact on gender inequity in cognitive functioning at older ages.
      Increases in educational attainment and the closing of the gender gap in
      education in many countries in Latin America and the Caribbean may thus result in
      both higher levels and a more gender-equitable distribution of later-life
      cognition among the future elderly in those countries.

PMID- 21732171
TI  - Hair cell toxicity in anti-cancer drugs: evaluating an anti-cancer drug library
      for independent and synergistic toxic effects on hair cells using the zebrafish
      lateral line.
AB  - Inner ear hair cell loss is the most common pathology seen after ototoxic drug
      injury. While certain drugs such as aminoglycosides and cisplatin are well-known
      to have dramatic ototoxic effects, it is probable that there are other drugs that
      cause occult degrees of hair cell loss and lesser degrees of hearing loss. Anti
      cancer drugs are particularly strong candidates due to their general
      cytotoxicity. We have screened a library of 88 anti-cancer drugs (National Cancer
      Institute Approved Oncology Drugs Set) for drugs that damage hair cells of the
      zebrafish lateral line. The screen identified four out of five known ototoxic
      drugs. The screen also identified four out of seven suspected ototoxic drugs
      (drugs that have isolated case reports of patients developing hearing loss after
      administration). Five additional drugs with no known ototoxicity were identified
      as potentially novel ototoxins. Additional dose-response curves were performed to
      evaluate relative toxicity. Since anti-cancer drugs are often used clinically in
      combination, we also performed dose-response curves for a variety of anti-cancer
      drug combinations and demonstrated synergistic toxicity in five out of ten drug
      combinations that we tested. These findings support the use of the zebrafish
      lateral line as a screening tool to detect ototoxic effects in drugs and also
      suggest that ototoxicity should be considered in terms of drug regimens rather
      than individual drugs.

PMID- 21732172
TI  - Purification and characterization of a lectin with high hemagglutination property
      isolated from Allium altaicum.
AB  - A lectin was purified from the leaves of Allium altaicum and corresponding gene
      was cloned. The lectin namely Allium altaicum agglutinin (AAA) was ~24 kDa
      homodimeric protein and similar to a typical garlic leaf lectin. It was
      synthesized as 177 amino acid residues pre-proprotein, which consisted of 28 and
      43 amino acid long N and C-terminal signal peptides, respectively. The plant
      expressed this protein more in scapes and flowers in comparison to the bulbs and
      leaves. Hemagglutination activity (with rabbit erythrocytes) was 1,428 fold
      higher as compared to Allium sativum leaf agglutinin (ASAL) although, the
      insecticidal activity against cotton aphid (Aphis gossypii) was relatively low.
      Glycan array revealed that AAA had higher affinity towards GlcAb1-3Galb as
      compared to ASAL. Homology analysis showed 57-94% similarity with other Allium
      lectins. The mature protein was expressed in E. coli as a fusion with SUMO
      peptide in soluble and biologically active form. Recombinant protein retained
      high hemagglutination activity.

PMID- 21732173
TI  - Effect of vitamin E on characteristics of liver mitochondrial fractions from cold
      exposed rats.
AB  - In cold exposed rats, it is known that vitamin E induces an increase in the
      respiration of the whole mitochondrial population isolated from liver. To obtain
      information on the effects of cold exposure and vitamin E treatment on the
      dynamics of mitochondrial population, we determined characteristics of rat liver
      mitochondrial fractions, resolved at 1,000 (M(1)), 3,000 (M(3)), and 10,000 g
      (M(10)). We found that cold exposure increased the liver content of total
      mitochondrial proteins irrespective of vitamin E treatment. Conversely, protein
      distribution among the mitochondrial subpopulations was differentially affected
      by cold and antioxidant integration. In a cold environment, the M(1) fraction,
      characterized by the highest O(2) consumption and H(2)O(2) production rates,
      underwent a remarkable protein content reduction, which was attenuated by vitamin
      E. These changes were dependent on the opposite effects of the two treatments on
      mitochondrial oxidative damage and susceptibility to swelling. The proteins of
      the other fractions, in which the above effects were lower, underwent smaller
      (M(3)) or no change (M(10)) in the treatment groups. The cold also led to an
      increase in O(2) consumption of the M(1) fraction which was accentuated by
      vitamin E treatment. This phenomenon and the vitamin-induced recovery of the M(1)
      proteins supply an explanation of the previously reported increase in the
      respiration of the whole mitochondrial population induced by vitamin E in the
      liver from cold exposed rats.

PMID- 21732174
TI  - O2 consumption rates along the growth curve: new insights into Trypanosoma cruzi
      mitochondrial respiratory chain.
AB  - Understanding the energy-transduction pathways employed by Trypanosoma cruzi, the
      etiological agent of Chagas disease, may lead to the identification of new
      targets for development of a more effective therapy. Herein, the contribution of
      different substrates for O(2) consumption rates along T. cruzi epimastigotes
      (Tulahuen 2 and Y strains) growth curve was evaluated. O(2) consumption rates
      were higher at the late stationary phase not due to an increase on succinate
      dehydrogenase activity. Antimycin A and cyanide did not totally inhibit the
      mitochondrial respiratory chain (MRC). Malonate at 10 or 25 mM was not a potent
      inhibitor of complex II. Comparing complex II and III, the former appears to be
      the primary site of H(2)O(2) release. An update on T. cruzi MRC is presented that
      together with our results bring important data towards the understanding of the
      parasite's MRC. The findings mainly at the stationary phase could be relevant for
      epimastigotes transformation into the metacyclic form, and in this sense deserves
      further attention.

PMID- 21732175
TI  - Role of Trypanosoma cruzi peroxiredoxins in mitochondrial bioenergetics.
AB  - Trypanosoma cruzi cytosolic (TcCPx) and mitochondrial tryparedoxin peroxidase
      (TcMPx) play a fundamental role in H(2)O(2) detoxification. Herein, mitochondrial
      bioenergetics was evaluated in cells that overexpressed TcCPx (CPx) and TcMPx
      (MPx) and in pTEX. In MPx, a higher expression was observed for TcCPx, and the
      same correlation was true for CPx. Differences in H(2)O(2) release among the
      overexpressing cells were detected when the mitochondrial respiratory chain was
      inhibited using antimycin A or thenoyltrifluoroacetone. MPx had higher O(2)
      consumption rates than pTEX and CPx, especially in the presence of oligomycin. In
      all of the cells, the mitochondrial membrane potential and the ATP levels were
      similar. Because of the mild uncoupling that was observed in MPx, the presence or
      induction of a proton transporter in the mitochondrial membrane is suggested when
      TcMPx is expressed at higher levels. Our results show a possible interplay
      between the cytosolic and mitochondrial antioxidant systems in a trypanosomatid.

PMID- 21732176
TI  - Genistein inhibits mitochondrial-targeted oxidative damage induced by beta
      amyloid peptide 25-35 in PC12 cells.
AB  - The antioxidative properties of genistein (Gen) have been demonstrated by our
      previous studies and others, but its potential mechanism was not very clear.
      Because of the key role of mitochondria in oxidant production, we wondered if
      mitochondria were one of Gen's neuroprotective targets. In the present study we
      investigated whether Gen has protective effects on mitochondria damaged by
      Abeta25-35. PC12 cells were pre-incubated with or without Gen for 2 h followed by
      the incubation with 20 MUM Abeta25-35 for another 24 h before mitochondrial
      membrane fluidity (MMF), mitochondrial membrane potential (MMP) , and
      mitochondrial redox state were measured. The results showed that Gen alleviated
      the decrease of MMF induced by Abeta25-35, and maintained the MMP. Additionally,
      Gen promoted the mitochondrial antioxidative capability through increasing the
      GSH/GSSG ratio, GPx activity and MnSOD protein expression in mitochondria.
      Moreover, Gen reversed the changes of ChAT mRNA and AChE mRNA expression in cells
      induced by Abeta25-35. These results suggested that Gen can protect the
      mitochondrial membrane and maintain redox state in mitochondria damaged by
      Abeta25-35.

PMID- 21732177
TI  - IL-6 induces lipolysis and mitochondrial dysfunction, but does not affect insulin
      mediated glucose transport in 3T3-L1 adipocytes.
AB  - Interleukin-6 (IL-6) has emerged as an important cytokine involved in the
      regulation of metabolism. However, the role of IL-6 in the etiology of obesity
      and insulin resistance is not fully understood. Mitochondria are key organelles
      of energy metabolism, and there is growing evidence that mitochondrial
      dysfunction plays a crucial role in the pathogenesis of obesity-associated
      insulin resistance. In this study, we determined the direct effect of IL-6 on
      lipolysis in adipocytes, and the effects of IL-6 on mitochondrial function were
      investigated. We found that cells treated with IL-6 displayed fewer lipids and an
      elevated glycerol release rate. Further, IL-6 treatment led to decreased
      mitochondrial membrane potential, decreased cellular ATP production, and
      increased intracellular ROS levels. The mitochondria in IL-6-treated cells became
      swollen and hollow with reduced or missing cristae. However, insulin-stimulated
      glucose transport was unaltered. PGC-1alpha, NRF1, and mtTFA mRNA levels were
      markedly increased, and the mitochondrial contents were also increased. Our
      results demonstrate that IL-6 can exert a direct lipolytic effect and induce
      mitochondrial dysfunction. However, IL-6 did not affect insulin sensitivity in
      adipocytes in vitro. We deduce that in these cells, enhanced mitochondrial
      biogenesis might play a compensatory role in glucose transport.

PMID- 21732178
TI  - The status of paediatric medicines initiatives around the world--What has
      happened and what has not?
AB  - PURPOSE: This review was conducted to examine the current status of paediatric
      medicines initiatives across the globe. METHODS: The authors made a non
      systematic descriptive review of current world situation. RESULTS: Two regions,
      the United States (US) and the European Union (EU), and the World Health
      Organization (WHO) have introduced strong paediatric initiatives to improve
      children's health through improving access to better paediatric medicines. The
      experience from the US initiative indicates that it is possible to stimulate
      development and study of paediatric medicines and provide important new
      information for improvement of paediatric therapy. The early results from the EU
      initiative are similarly encouraging. In Canada, Japan, Australia and other
      developed countries, specific paediatric medicines initiatives have been less
      extensive and weaker, with modest results. Disappointingly, current evidence
      suggests that results from clinical trials outside the US often do not benefit
      children in the country in which the trials were largely conducted.
      Pharmaceutical companies that have derived a financial benefit commensurate with
      the cost of doing the paediatric trials in one country do not seem to be making
      the results of these trials available to all countries if there is no financial
      incentive to the company. The WHO campaign 'make medicines child size' has
      produced substantive accomplishments in building improved foundations to improve
      mechanisms that will enhance children's access to critical medicines in resource
      limited settings. However, practically all of this work has been performed using
      an amalgamation of short-term funding from a variety of sources as opposed to a
      sustained, programmatic commitment. CONCLUSIONS: Although much still needs to be
      done, it's clear that with concerted efforts and appropriate resources, change is
      possible but slow. Retaining and fostering public and political interest in
      paediatric medicines is challenging, but pivotal for success.

PMID- 21732179
TI  - Evolution of the IL17 receptor family in chordates: a new subfamily IL17REL.
AB  - The human interleukin 17 receptor (IL17R) family plays a critical role in
      inflammatory responses and contributes to the pathology of many autoimmune
      diseases. So far, five members, IL17RA to IL17RE, have been identified. Recently,
      some IL17R genes have been identified in non-mammalian species, such as zebrafish
      IL17RD; however, there are no reports on the evolutionary history of this complex
      gene family through comparative phylogenetic approaches. Here, we concentrated on
      the IL17R evolution in chordates. There are two IL17Rs in the genome of the basal
      chordate amphioxus: IL17RA and IL17RD. After two rounds of whole genome
      duplications, these two IL17R genes expanded into five early vertebrate IL17R
      genes, IL17RA to IL17RE. IL17RA and IL17RD are found in most vertebrates, whereas
      the other three, IL17RB, ILR17RC, and IL17RE, underwent some loss in vertebrates
      during evolution. Our sequence and structure analyses reveal functional
      similarities and distinctions between the different IL17Rs. Based on similarity
      searches for IL17R-like proteins within chordate sequences, a group of IL17RE
      like (IL17REL) proteins were identified from mammalians to lower vertebrates. In
      silico and expression analyses on the novel IL17RELs showed that this group of
      receptors is highly conserved across species, indicating that IL17REL may
      represent a unique subfamily of IL17Rs.

PMID- 21732180
TI  - The role of MHC class I allele Mamu-A*07 during SIV(mac)239 infection.
AB  - Virus-specific CD8(+) T cells play an important role in controlling HIV/SIV
      replication. These T cells recognize intracellular pathogen-derived peptides
      displayed on the cell surface by individual MHC class I molecules. In the SIV
      infected rhesus macaque model, five Mamu class I alleles have been thoroughly
      characterized with regard to peptide binding, and a sixth was shown to be
      uninvolved. In this study, we describe the peptide binding of Mamu-A1*007:01
      (formerly Mamu-A*07), an allele present in roughly 5.08% of Indian-origin rhesus
      macaques (n = 63 of 1,240). We determined a preliminary binding motif by eluting
      and sequencing endogenously bound ligands. Subsequently, we used a positional
      scanning combinatorial library and panels of single amino acid substitution
      analogs to further characterize peptide binding of this allele and derive a
      quantitative motif. Using this motif, we selected and tested 200 peptides derived
      from SIV(mac)239 for their capacity to bind Mamu-A1*007:01; 33 were found to bind
      with an affinity of 500 nM or better. We then used PBMC from SIV-infected or
      vaccinated but uninfected, A1*007:01-positive rhesus macaques in IFN-gamma
      Elispot assays to screen the peptides for T-cell reactivity. In all, 11 of the
      peptides elicited IFN-gamma(+) T-cell responses. Six represent novel A1*007:01
      restricted epitopes. Furthermore, both Sanger and ultradeep pyrosequencing
      demonstrated the accumulation of amino acid substitutions within four of these
      six regions, suggestive of selective pressure on the virus by antigen-specific
      CD8(+) T cells. Thus, it appears that Mamu-A1*007:01 presents SIV-derived
      peptides to antigen-specific CD8(+) T cells and is part of the immune response to
      SIV(mac)239.

PMID- 21732181
TI  - Chemical composition and nutritional value of unripe banana flour (Musa
      acuminata, var. Nanicao).
AB  - Banana flour obtained from unripe banana (Musa acuminata, var. Nanicao) under
      specific drying conditions was evaluated regarding its chemical composition and
      nutritional value. Results are expressed in dry weight (dw). The unripe banana
      flour (UBF) presented a high amount of total dietary fiber (DF) (56.24 g/100 g),
      which consisted of resistant starch (RS) (48.99 g/100 g), fructans (0.05 g/100 g)
      and DF without RS or fructans (7.2 g/100 g). The contents of available starch
      (AS) (27.78 g/100 g) and soluble sugars (1.81 g/100 g) were low. The main
      phytosterols found were campesterol (4.1 mg/100 g), stigmasterol (2.5 mg/100 g)
      and beta-sitosterol (6.2 mg/100 g). The total polyphenol content was 50.65 mg
      GAE/100 g. Antioxidant activity, by the FRAP and ORAC methods, was moderated,
      being 358.67 and 261.00 MUmol of Trolox equivalent/100 g, respectively. The
      content of Zn, Ca and Fe and mineral dialyzability were low. The procedure used
      to obtain UBF resulted in the recovery of undamaged starch granules and in a low
      energy product (597 kJ/100 g).

PMID- 21732182
TI  - Use of fluorescent lectin binding to distinguish Teladorsagia circumcincta and
      Haemonchus contortus eggs, third-stage larvae and adult worms.
AB  - Lectin binding to carbohydrates on parasite surfaces has been investigated as a
      method of distinguishing adult worms, eggs and sheathed and exsheathed L3 of
      Teladorsagia circumcincta and Haemonchus contortus, economically important
      abomasal parasites in temperate climates. Both species were maintained as pure
      laboratory cultures of field isolates from New Zealand. Each of the four life
      cycle stages could be distinguished by the binding of at least one lectin: adult
      worms by Sambucus nigra agglutinin (SNA); eggs by peanut agglutinin (PNA),
      ConcavalinA and Lens culinaris agglutinin (LCA); exsheathed L3 by Griffonia
      simplicifolia-I lectin (GSL-I) and Lotus tetragonolobus lectin (LTL) and sheathed
      L3 by Aleuria aurantia lectin (AAL). The whole surface of both adult T.
      circumcincta and H. contortus strongly bound lectins specific for N
      acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), mannose and fucose,
      but the two species could be distinguished by SNA binding only to T.
      circumcincta. Eggs could be distinguished by the binding of mannose-specific PNA
      to H. contortus and GalNAc-specific LCA and PSA to T. circumcincta eggs. GalNAc,
      GlcNAc and mannose lectins bound to the cuticle and over the excretory pores of a
      large proportion of sheathed L3 of both species, but only the H. contortus
      surface had exposed fucose or sialic acid complexes. The distinguishing lectin
      for sheathed L3 was AAL, which did not bind to T. circumcincta, but bound weakly
      to the head region of all fresh H. contortus and to 50-90% after 3 months
      storage. The cuticle of exsheathed L3 was unresponsive to all 19 lectins, and any
      binding was restricted to the head and tail regions. L3 exsheathed after 2-4
      months storage could be distinguished by the binding of GSL-I and LTL to H.
      contortus but not to T. circumcincta. Lectin binding could be a useful adjunct in
      identifying L3, but lacked the consistency to be definitive, whereas it could be
      further developed as a practical method of distinguishing parasitic nematodes at
      other stages in the life cycle, particularly the eggs.

PMID- 21732183
TI  - Synergistic activity of Cyt1A from Bacillus thuringiensis subsp. israelensis with
      Bacillus sphaericus B101 H5a5b against Bacillus sphaericus B101 H5a5b-resistant
      strains of Anopheles stephensi Liston (Diptera: Culicidae).
AB  - Integrated vector control is an effective and essential part of any successful
      vector control program. Increasing insecticide resistance requires strategies to
      prolong the use of highly effective vector control compounds. Synergistic
      activity between current effective pesticides is a powerful tool and is one such
      strategy. In the current study, Cyt1A from Bacillus thurigiensis subsp.
      israelensis and Bacillus sphaericus B101H5aH5b Bs were evaluated for the
      synergistic activity against B. sphaericus-resistant strains of Anopheles
      stephensi. The combinations of Cyt1A and B. sphaericus were found to act
      synergistically and were greatly enhanced at different ratios. A ratio of 1:4 of
      Cyt1A and Bs was 13,200-fold more toxic at LC(90) against the Bs-resistant
      strains of A. stephensi than was Bs alone and this high level of activity
      resulted from synergism between Cyt1A toxin and Bs. Our results therefore suggest
      that Cyt1A may enhance toxicity by facilitating the binding or insertion of the
      binary toxins to the microvillar membrane.

PMID- 21732184
TI  - Research and increase of expertise in arachno-entomology are urgently needed.
AB  - Considering the contents of international journals of parasitology dealing with
      broader topics inside this field show that rather a few papers appear with
      studies in the discipline of arachno-entomology. In the journals Journal of
      Parasitology, Parasitology Research and Trends in Parasitology, the relations of
      published papers on protozoology, helminthology and arachno-entomology showed
      that in all three journals, papers on protozoans were the most common, while
      those on helminths of any kind reached the second place being rather as common as
      the protozoan papers in Parasitology Research and in the Journal of Parasitology.
      In Trends of Parasitology, however, the papers on helminths reached only about
      25% of the numbers published on protozoan topics. But in all three journals-and
      this is important-the papers on arachno-entomological themes were scarce reaching
      less than the half of the protozoan papers in Parasitology Research, and only
      about 15% in the Journal of Parasitology and in the Trends of Parasitology. These
      disproportions between the three great subdivisions of targets in the focus of
      parasitological research are dangerous, since this lack exists already for
      several decades and thus led to a backlog of unsolved increasing problems that
      are caused by ticks, mites, insects and/or parasitic crustaceans especially in
      times of intensive globalization and global warming. Studies on the biology,
      vectorship, invasion and spreading of wanted vectors and on the control of pests
      and parasites belonging to the field of arachno-entomology are urgently needed.

PMID- 21732185
TI  - Pitfalls in multidetector computed tomography imaging of traumatic spinal
      injuries.
AB  - The advent of multidetector computed tomography (MDCT) has largely supplanted
      plain radiography as the recommended primary imaging modality for the evaluation
      of acute spinal injuries. Although MDCT is highly sensitive and specific for bony
      injuries, errors in diagnosis can still occur. Knowledge of the possible imaging
      pitfalls on MDCT, leading to either misdiagnosis of fractures or missed
      fractures, is vital in ensuring an accurate diagnosis. This paper serves to
      highlight conditions that can mimic or reduce the sensitivity for the detection
      of acute spinal injuries, as well as demonstrate imaging findings which aid in
      the detection and diagnosis of subtle spinal injuries. Review areas for
      clinically relevant extra-spinal findings in the context of trauma will also be
      discussed.

PMID- 21732186
TI  - Cross-species correlation between queen mating numbers and worker ovary sizes
      suggests kin conflict may influence ovary size evolution in honeybees.
AB  - During social evolution, the ovary size of reproductively specialized honey bee
      queens has dramatically increased while their workers have evolved much smaller
      ovaries. However, worker division of labor and reproductive competition under
      queenless conditions are influenced by worker ovary size. Little comparative
      information on ovary size exists in the different honey bee species. Here, we
      report ovariole numbers of freshly dissected workers from six Apis species from
      two locations in Southeast Asia. The average number of worker ovarioles differs
      significantly among species. It is strongly correlated with the average mating
      number of queens, irrespective of body size. Apis dorsata, in particular, is
      characterized by numerous matings and very large worker ovaries. The relation
      between queen mating number and ovary size across the six species suggests that
      individual selection via reproductive competition plays a role in worker ovary
      size evolution. This indicates that genetic diversity, generated by multiple
      mating, may bear a fitness cost at the colony level.

PMID- 21732187
TI  - FoxP3- and CD8-positive Infiltrating Immune Cells Together Determine Clinical
      Outcome in Colorectal Cancer.
AB  - Immune cells are known to affect clinical outcome in colorectal cancer. Subsets
      of immune cells can both support and inhibit immunological interaction with tumor
      cells. We examined the clinical impact of T cells that are supposed to be
      responsible for the down regulation of a T cell response: regulatory T cells or
      Tregs. The study population (n = 76) consisted of a random population of
      colorectal cancer patients who did not receive any (neo-) adjuvant therapy, with
      a median follow-up time of 7.3 years (range 0.1-23.1 years). Expression of FoxP3
      was used as an immunohistochemical marker to identify Tregs. We considered FoxP3+
      cells present in tumor stroma and tumor epithelium separately, and related
      results to clinical outcome and to data on CD8+ immune cell infiltration that we
      previously obtained in the same patient cohort. All samples showed presence of
      Foxp3+ cells and in the majority of the patients (85.5%) these cells were also
      present in the tumor epithelial compartment. A relative high level of Foxp3+
      cells in the tumor epithelium was significantly related to down regulation of HLA
      Class I expression (p-value 0.03). There was a trend, but no significant
      relation, towards a longer overall survival (p-value; 0.084) and disease-free
      survival (p-value; 0.073) when high levels of Foxp3+ cells were present in the
      tumor epithelium. More importantly, the ratio of CD8+/Foxp3+ cells did show a
      significant correlation with distant-recurrence-free survival. This was the case
      for both Foxp3+ cells specifically located in the tumor epithelium (p-value
      0.024) as well as in the stroma compartment (p-value 0.018). Unfortunately due to
      the small sample size the ratios did not retain their statistical significance in
      multivariate analysis. These results provide further evidence that local
      interactions in the cancer microenvironment between tumor cells and immune cells
      are not only determined by tumor cell-related factors like HLA expression, but
      also by interactions among immune cells.

PMID- 21732189
TI  - Endogenous tagging of the murine transcription factor Sox5 with hemaglutinin for
      functional studies.
AB  - Gene expression is usually studied at the transcript level rather than at the
      protein level due to the lack of a specific and sensitive antibody. A way to
      overcome this is to fuse to the protein of interest an immunoreactive tag that
      has well-characterized antibodies. This epitope tagging approach is often used
      for in vitro experiments but for in vivo studies, the success rate of protein
      tagging has not been extensively analyzed and our study seeks to cover the void.
      A small epitope, hemaglutinin derived from the influenza virus was used to tag a
      transcription factor, Sox5 at the N-terminal via homologous recombination in the
      mouse. Sox5 is part of the Sry-related high-mobility-group box gene family and
      plays multiple roles in essential biological processes. Understanding of its
      molecular function in relation to its biological roles remains incomplete. In our
      study, we show that the longer isoform of Sox5 can be tagged endogenously with
      hemaglutinin without affecting its biological function in vivo. The tagged
      protein is easily and specifically detected with an anti-hemaglutinin antibody
      using immunohistochemistry with its expression matching the endogenous expression
      of Sox5. Immunoprecipitation of Sox5 was also carried out successfully using an
      anti-hemaglutinin antibody. The transgenic line generated from this study is
      predicted to be useful for future experiments such as co-immunoprecipitation and
      chromatin immunoprecipitation, allowing the further understanding of Sox5.
      Lastly, this approach can be easily employed for the investigation of other
      transcription factors and proteins in vivo to overcome technical limitations such
      as antibody cross-reactivity and to perform isoform-specific studies.

PMID- 21732190
TI  - Does estrogen have any real effect on voiding dysfunction in women?
AB  - For many years, estrogen has been used to treat lower urinary tract dysfunction
      in postmenopausal women. The data supporting this practice vary. Large multi
      institutional studies have shown little role for systemic estrogens in the
      treatment of urinary incontinence. Vaginal estrogen preparations show superiority
      to systemic estrogens for the treatment of irritative voiding symptoms in meta
      analysis, but there is significant study heterogeneity and the practice remains
      debatable. Data from randomized controlled trials support estrogen use in the
      prevention of recurrent urinary tract infections. This article reviews the
      relevant literature addressing the role of estrogen therapy in urinary
      incontinence, irritative voiding symptoms, and recurrent urinary tract
      infections.

PMID- 21732191
TI  - The function of dog models in developing gene therapy strategies for human
      health.
AB  - The domestic dog is of great benefit to humankind, not only through companionship
      and working activities cultivated through domestication and selective breeding,
      but also as a model for biomedical research. Many single-gene traits have been
      well-characterized at the genomic level, and recent advances in whole-genome
      association studies will allow for better understanding of complex, multigenic
      hereditary diseases. Additionally, the dog serves as an invaluable large animal
      model for assessment of novel therapeutic agents. Thus, the dog has filled a
      crucial step in the translation of basic research to new treatment regimens for
      various human diseases. Four well-characterized diseases in canine models are
      discussed as they relate to other animal model availability, novel therapeutic
      approach, and extrapolation to human gene therapy trials.

PMID- 21732192
TI  - The emerging role for rat models in gene discovery.
AB  - Rat models have been used for many decades to study physiological and
      pathophysiological mechanisms. Prior to the release of the rat genome and new
      technologies for targeting gene manipulation, the rat had been the underdog in
      the genomics era, despite the abundance of physiological data compared to the
      mouse. The overarching goal of biomedical research is to improve health and
      advance medical science. Translating human disease gene discovery and validation
      in the rat, through the use of emerging technologies and integrated tools and
      databases, is providing power to understand the genetics, environmental
      influences, and biology of disease. In this review we briefly outline the rat
      models, bioinformatics tools, and technologies that are changing the landscape of
      translational research. The strategies used to translate disease traits to genes
      to function, and, ultimately, to improve human health is discussed. Finally, our
      perspective on how rat models will continue to positively impact biomedical
      research is provided.

PMID- 21732193
TI  - Genetic analysis of iron-deficiency effects on the mouse spleen.
AB  - Iron homeostasis is crucial to many biological functions in nearly all organisms,
      with roles ranging from oxygen transport to immune function. Disruption of iron
      homeostasis may result in iron overload or iron deficiency. Iron deficiency may
      have severe consequences, including anemia or changes in immune or
      neurotransmitter systems. Here we report on the variability of phenotypic iron
      tissue loss and splenomegaly and the associated quantitative trait loci (QTLs),
      polymorphic areas in the mouse genome that may contain one or more genes that
      play a role in spleen iron concentration or spleen weight under each dietary
      treatment. Mice from 26 BXD/Ty recombinant inbred strains, including the parent
      C57BL/6 and DBA/2 strains, were randomly assigned to adequate iron or iron
      deficient diets at weaning. After 120 days, splenomegaly was measured by spleen
      weight, and spleen iron was assessed using a modified spectrophotometry
      technique. QTL analyses and gene expression comparisons were then conducted using
      the WebQTL GeneNetwork. We observed wide, genetic-based variability in
      splenomegaly and spleen iron loss in BXD/Ty recombinant inbred strains fed an
      iron-deficient diet. Moreover, we identified several suggestive QTLs. Matching
      our QTLs with gene expression data from the spleen revealed candidate genes. Our
      work shows that individual differences in splenomegaly response to iron
      deficiency are influenced at least partly by genetic constitution. We propose
      mechanistic hypotheses by which splenomegaly may result from iron deficiency.

PMID- 21732194
TI  - Genetic determinants for intramuscular fat content and water-holding capacity in
      mice selected for high muscle mass.
AB  - Intramuscular fat content and water-holding capacity are important traits in
      livestock as they influence meat quality, nutritive value of the muscle, and
      animal health. As a model for livestock, two inbred lines of the Berlin Muscle
      Mouse population, which had been long-term selected for high muscle mass, were
      used to identify genomic regions affecting intramuscular fat content and water
      holding capacity. The intramuscular fat content of the Musculus longissimus was
      on average 1.4 times higher in BMMI806 than in BMMI816 mice. This was accompanied
      by a 1.5 times lower water-holding capacity of the Musculus quadriceps in BMMI816
      mice. Linkage analyses with 332 G(3) animals of reciprocal crosses between these
      two lines revealed quantitative trait loci for intramuscular fat content on
      chromosome 7 and for water-holding capacity on chromosome 2. In part, the
      identified loci coincide with syntenic regions in pigs in which genetic effects
      for the same traits were found. Therefore, these muscle-weight-selected mouse
      lines and the produced intercross populations are valuable genetic resources to
      identify genes that could also contribute to meat quality in other species.

PMID- 21732195
TI  - A randomized trial to improve patient-centered care and hypertension control in
      underserved primary care patients.
AB  - BACKGROUND: African Americans and persons with low socioeconomic status (SES) are
      disproportionately affected by hypertension and receive less patient-centered
      care than less vulnerable patient populations. Moreover, continuing medical
      education (CME) and patient-activation interventions have infrequently been
      directed to improve the processes of care for these populations. OBJECTIVE: To
      compare the effectiveness of patient-centered interventions targeting patients
      and physicians with the effectiveness of minimal interventions for underserved
      groups. DESIGN: Randomized controlled trial conducted from January 2002 through
      August 2005, with patient follow-up at 3 and 12 months, in 14 urban, community
      based practices in Baltimore, Maryland. PARTICIPANTS: Forty-one primary care
      physicians and 279 hypertension patients. INTERVENTIONS: Physician communication
      skills training and patient coaching by community health workers. MAIN MEASURES:
      Physician communication behaviors; patient ratings of physicians' participatory
      decision-making (PDM), patient involvement in care (PIC), reported adherence to
      medications; systolic and diastolic blood pressure (BP) and BP control. KEY
      RESULTS: Visits of trained versus control group physicians demonstrated more
      positive communication change scores from baseline (-0.52 vs. -0.82, p = 0.04).
      At 12 months, the patient+physician intensive group compared to the minimal
      intervention group showed significantly greater improvements in patient report of
      physicians' PDM (beta = +6.20 vs. -5.24, p = 0.03) and PIC dimensions related to
      doctor facilitation (beta = +0.22 vs. -0.17, p = 0.03) and information exchange
      (beta = +0.32 vs. -0.22, p = 0.005). Improvements in patient adherence and BP
      control did not differ across groups for the overall patient sample. However,
      among patients with uncontrolled hypertension at baseline, non-significant
      reductions in systolic BP were observed among patients in all intervention groups
      the patient+physician intensive (-13.2 mmHg), physician intensive/patient minimal
      (-10.6 mmHg), and the patient intensive/physician minimal (-16.8 mmHg), compared
      to the patient+physician minimal group (-2.0 mmHg). CONCLUSION: Interventions
      that enhance physicians' communication skills and activate patients to
      participate in their care positively affect patient-centered communication,
      patient perceptions of engagement in care, and may improve systolic BP among
      urban African-American and low SES patients with uncontrolled hypertension.

PMID- 21732197
TI  - Cultural, economic, and psychological predictors of colonoscopy in a national
      sample.
AB  - BACKGROUND: Although colorectal cancer (CRC) is the second leading cause of
      cancer death among adults in the US and colonoscopy is efficacious in reducing
      morbidity and mortality from CRC, screening rates are sub-optimal. Understanding
      the socioeconomic, cultural, and health care context within which decisions about
      colonoscopy are made allows physicians to address patients' most salient beliefs
      and values and other constraints when making screening recommendations.
      OBJECTIVE: To evaluate the direct and interactive effects of socioeconomics,
      health care variables, psychological characteristics, and cultural values on
      colonoscopy use. DESIGN, SETTING, PARTICIPANTS: National survey completed between
      January-August 2009 in a random sample of African American, white, and Hispanic
      adults ages 50-75 without cancer (n = 582). MAIN MEASURE: Self-reported
      colonoscopy use. KEY RESULTS: Only 59% of respondents reported having a
      colonoscopy. The likelihood of colonoscopy increased with having health insurance
      (OR = 2.82, 95% CI = 1.24, 6.43, p = 0.004), and increasing age (OR = 1.40, 95%
      CI = 1.11, 1.77, p = 0.001). In addition, respondents with greater self-efficacy
      were more likely to have a colonoscopy (OR = 2.41, 95% CI = 1.35, 4.29, p =
      0.003). CONCLUSIONS: Programs that help patients to overcome access and
      psychological barriers to screening are needed.

PMID- 21732198
TI  - Changes in drug use are associated with health-related quality of life
      improvements among methadone maintenance patients with HIV/AIDS.
AB  - PURPOSE: This longitudinal study assessed the changes in drug use patterns and
      health-related quality of life (HRQL) among HIV-positive drug users in the first
      methadone maintenance treatment (MMT) cohort in Vietnam. METHODS: A secondary
      analysis was conducted on 370 HIV-positive drug users (age: mean +/- SD: 29.5 +/-
      5.9 years; 95.7% men). Modified WHOQOL-BREF, self-report, and opioid confirmatory
      urine tests were used to assess HRQL and drug use behaviours at baseline, 3, 6,
      and 9 months. Generalized estimating equations (GEE) models were constructed to
      adjust for intra-individual correlations. RESULTS: MMT response rate after 9
      months was 89.9%. Rates of positive heroin urine tests rapidly decreased at the
      first trimester (18.1%) and then stabilized during the next 2 trimesters (11.8
      and 14.4%). Among patients with continued drug use, frequency of use decreased
      from 3.4 to 0.7 time/day. Improvements in HRQL were large over the course of the
      study and highest in the psychological domain. Adjusting for propensity score in
      GEE models, ongoing heroin use during MMT resulted in large decrements in all
      HRQL domains. CONCLUSIONS: MMT improved the outcomes of treatment for drug users
      in ways that might facilitate success of antiretroviral therapy. Integrating MMT
      to HIV care and treatment services could be beneficial in injection-driven HIV
      epidemics in resource-scare settings.

PMID- 21732199
TI  - Rating the methodological quality in systematic reviews of studies on measurement
      properties: a scoring system for the COSMIN checklist.
AB  - BACKGROUND: The COSMIN checklist is a standardized tool for assessing the
      methodological quality of studies on measurement properties. It contains 9 boxes,
      each dealing with one measurement property, with 5-18 items per box about design
      aspects and statistical methods. Our aim was to develop a scoring system for the
      COSMIN checklist to calculate quality scores per measurement property when using
      the checklist in systematic reviews of measurement properties. METHODS: The
      scoring system was developed based on discussions among experts and testing of
      the scoring system on 46 articles from a systematic review. Four response options
      were defined for each COSMIN item (excellent, good, fair, and poor). A quality
      score per measurement property is obtained by taking the lowest rating of any
      item in a box ("worst score counts"). RESULTS: Specific criteria for excellent,
      good, fair, and poor quality for each COSMIN item are described. In defining the
      criteria, the "worst score counts" algorithm was taken into consideration. This
      means that only fatal flaws were defined as poor quality. The scores of the 46
      articles show how the scoring system can be used to provide an overview of the
      methodological quality of studies included in a systematic review of measurement
      properties. CONCLUSIONS: Based on experience in testing this scoring system on 46
      articles, the COSMIN checklist with the proposed scoring system seems to be a
      useful tool for assessing the methodological quality of studies included in
      systematic reviews of measurement properties.

PMID- 21732200
TI  - Evaluation of an immunochromatographic assay: Giardia-Strip(r) (Coris BioConcept)
      for detection of Giardia intestinalis in human fecal specimens.

PMID- 21732201
TI  - Nontuberculous mycobacteria infection in solid organ transplant recipients.
AB  - Although advances in surgical technique, drug-induced immunosuppression, and
      supportive medical therapy have led to improved survival and quality of live
      after solid organ transplantations, infections still represent a major threat for
      transplant recipients.Infections with non tuberculous mycobacteria (NTM) are
      infrequent, but can be associated with relevant morbidity and mortality. With the
      exception of few comprehensive studies, the available literature consists
      predominantly of case reports and institutional experiences. This article reviews
      NTM infection in the setting of solid organ transplant (SOT) recipients dealing
      with clinical features, diagnosis, treatment and outcome. Published studies have
      documented a protean presentation of NTM infection in SOT recipients which may
      include skin and soft tissue lesions, osteoarticular infections and
      pleuropulmonary disease. An aggressive approach including histopathologic
      examination and acid-fast bacilli culture of aspirates or biopsy specimens from
      involved sites are essential for diagnosis. A combined treatment of debridement
      surgery, reduction of immunosuppressive medications and/or antimycobacterial
      drugs is frequently associated with a favorable outcome. It is strongly
      emphasized that a high index of suspicion for NTM infection should be maintained
      when managing SOT recipients with unusual clinical manifestations. Early
      diagnosis and initiation of therapy are essential to prevent morbidity and
      mortality in this vulnerable population.

PMID- 21732202
TI  - Norovirus infections in children under 5 years of age hospitalized due to the
      acute viral gastroenteritis in northeastern Poland.
AB  - The primary aim of this study was to evaluate the frequency and seasonality of
      norovirus infection in hospitalized Polish children under 5 years of age, and a
      secondary aim was to compare the clinical severity of norovirus and rotavirus
      disease. The prospective surveillance study was carried out from July 2009
      through June 2010. Stool samples from 242 children hospitalized due to acute
      viral gastroenteritis were tested for rotavirus group A and adenovirus with
      commercial immunochromatographic test and for norovirus with EIA assay. Single
      norovirus infection was found in 35/242 (14.5%) patients and in a further 5
      (2.1%) children as co-infection with rotavirus. Overall, norovirus was detected
      in 16.5% of stool specimens. Norovirus infections tended to peak from October to
      November and again from February to March. In autumn months and in February, the
      proportion of norovirus gastroenteritis cases was equal or even surpassed those
      of rotavirus origin. Both norovirus and rotavirus infections most commonly
      affected children between 12 and 23 months of age. The low-grade or no fever was
      significantly more common in children infected with norovirus (94.3%) compared to
      rotavirus cases (52.9%). Overall, norovirus gastroenteritis was less severe than
      rotavirus disease with regard to 20-point severity scale (p < 0.05). Noroviruses
      have emerged as a relevant cause of acute gastroenteritis in Polish children.
      There is a great need for introducing routine norovirus testing of hospitalized
      children with gastroenteritis.

PMID- 21732203
TI  - A functionally required unfoldome from the plant kingdom: intrinsically
      disordered N-terminal domains of GRAS proteins are involved in molecular
      recognition during plant development.
AB  - The intrinsic disorder is highly abundant in eukaryotic genomes. In the animal
      kingdom, numerous intrinsically disordered proteins (IDPs) have been
      characterized, especially in cell signalling and transcription regulation. An
      intrinsically disordered region often folds in different structures allowing an
      IDP to recognize and bind different partners at various binding interfaces. In
      contrast, there have only been a few reports of IDPs from the plant kingdom.
      Plant-specific GRAS proteins play critical and diverse roles in plant development
      and signalling and often act as integrators of signals from multiple plant growth
      regulatory inputs. Using computational and bioinformatics tools, we demonstrate
      here that the GRAS proteins are intrinsically disordered, thus forming the first
      functionally required unfoldome in the plant kingdom. Furthermore, the N-terminal
      domains of GRAS proteins are predicted to contain numerous Molecular Recognition
      Features (MoRFs), short interaction-prone segments that are located within
      extended disorder regions and are able to recognize their interacting partners
      and to undergo disorder-to-order transitions upon binding to these specific
      partners. Overlapping with the relatively conserved motifs in the N-terminal
      domains of GRAS proteins, these predicted MoRFs represent the potential protein
      protein binding sites and may be involved in molecular recognition during plant
      development. This study enables us to propose a conceptual framework that guides
      future experimental approaches to understand structure-function relationships of
      the entire GRAS family.

PMID- 21732204
TI  - Implementation intentions and imagery: individual and combined effects on
      prospective memory among young adults.
AB  - Prospective memory (PM) has been found to benefit from implementation intentions
      (i.e., "when I see X, I will do Y"). However, to date, it is unclear whether
      implementation intentions must incorporate imagery in order to produce a positive
      effect on PM, or whether the verbal statement alone is sufficient. It is also
      equivocal whether the use of visual imagery alone improves PM, absent an
      intentional statement. The present study investigated the individual influences
      of implementation intentions and imagery, as well as their combined effect, on
      PM. A total of 64 undergraduates were placed into one of four instructional
      conditions-read-only, implementation intention, imagery, or combined-and were
      then tested on a laboratory PM task. The results revealed that participants in
      the implementation intention, imagery, and combined groups completed
      significantly more PM tasks than did participants in the read-only group, but
      they did not differ from one another. Combining implementation intentions and
      imagery, however, did not improve PM performance over either strategy alone.
      Additionally, the implementation intention and imagery groups outperformed the
      read-only group on a secondary ongoing digit detection task. The results of this
      study suggest that implementation intentions do not require imagery to be
      effective in improving PM, and that imagery alone has positive effects on PM.
      Finally, the results of the ongoing digit detection task suggest that the use of
      implementation intentions and imagery might provide for automatic identification
      and processing of environmental cues.

PMID- 21732205
TI  - Exploring metacognitive accuracy in visual search.
AB  - For decades, researchers have examined visual search. Much of this work has
      focused on the factors (e.g., movement, set size, luminance, distractor features
      and proximity) that influence search speed. However, no research has explored
      whether people are aware of the influence of these factors. For instance,
      increases in set size will typically slow down target detection; yet no research
      has measured participants' metacognitive awareness of this phenomenon. The
      present research explores this area by integrating a visual search task with a
      metacognitive monitoring paradigm. All of the explored factors influenced search
      latency. However, all of the factors except target presence influenced ratings.
      Saliency and suppression are discussed as two possible explanations for the
      results. Future directions for extending the theory and the practical benefits of
      this research are also outlined.

PMID- 21732207
TI  - In-hospital death following inpatient surgical procedures in the United States,
      1996-2006.
AB  - BACKGROUND: Over the past decade, improvements in perioperative care have been
      widely introduced throughout the United States, yet there is no clear indication
      that the death rate following surgery has improved. We sought to evaluate the
      number of deaths after surgery in the United States over a 10-year period and to
      evaluate trends in postoperative mortality. METHODS: Using the National Hospital
      Discharge Survey, we identified patients who underwent a surgical procedure and
      subsequently died in the hospital within 30 days of admission. RESULTS: In 1996
      there were 12,250,000 hospitalizations involving surgery, rising to 13,668,000 in
      2006. Postoperative deaths, however, declined during this same period, from
      201,000 to 156,000 (P < 0.01), giving a postoperative in-hospital death ratio
      (death per hospitalization) of 1.64 and 1.14% (P < 0.001), respectively, for the
      two time frames. CONCLUSIONS: The death rate following surgery is substantial but
      appears to have improved. Such mortality statistics provide an essential measure
      of the public health impact of surgical care. Incorporating mortality statistics
      following therapeutic intervention is an essential strategy for regional and
      national surveillance of care delivery.

PMID- 21732208
TI  - Outcomes of laparoscopic versus open colectomy in elective surgery for
      diverticulitis.
AB  - BACKGROUND: The role of laparoscopy in the management of diverticular disease is
      evolving. Concerns were raised in the past because laparoscopic resection for
      diverticulitis is often difficult and occasionally hazardous. This study was
      undertaken to evaluate the difference in overall outcomes between elective open
      and laparoscopic surgery with or without anastomosis for diverticulitis. METHODS:
      Using the National Inpatient Sample (NIS) database, clinical data of patients who
      underwent elective open and laparoscopic surgery (lap) for diverticulitis from
      2002 to 2007 were collected and analyzed. Patients who underwent emergent surgery
      were excluded. RESULTS: A total of 124,734 patients underwent elective surgery
      for diverticulitis: open, 110,172 (88.3%); lap, 14,562 (11.7%). The overall
      intraoperative complication rate was significantly lower in the laparoscopy group
      (0.63% vs. 1.15%, P < 0.01). However, there was no significant difference
      observed in ureteral injury between groups (open, 0.17%; lap, 0.12%, P = 0.15).
      All evaluated postoperative complications (ileus, abdominal abscess, leak, wound
      infection, bowel obstruction, urinary tract infection, pneumonia, respiratory
      failure, venous thromboembolism) were significantly higher for the open
      procedures. The laparoscopy group had a shorter mean hospital stay (lap, 5.06
      days; open, 6.68 days, P < 0.01) and lower total hospital charges (lap, $36,389;
      open, $39,406, P < 0.01) than the open group. Also, mortality was four times
      higher in the open group (open, 0.54%; lap, 0.13%, P < 0.01). CONCLUSIONS: The
      laparoscopic operation was associated with lower morbidity, lower mortality,
      shorter hospital stay, and lower hospital charges compared to the open operation
      for diverticulitis. Elective laparoscopic surgery for diverticulitis is safe and
      can be considered the preferred operative option.

PMID- 21732209
TI  - A segmental labeling strategy for unambiguous determination of domain-domain
      interactions of large multi-domain proteins.
AB  - NMR structural determination of large multi-domain proteins is a challenging task
      due to significant spectral overlap with a particular difficulty in unambiguous
      identification of domain-domain interactions. Segmental labeling is a NMR
      strategy that allows for isotopically labeling one domain and leaves the other
      domain unlabeled. This significantly simplifies spectral overlaps and allows for
      quick identification of domain-domain interaction. Here, a novel segmental
      labeling strategy is presented for detection of inter-domain NOEs. To identify
      domain-domain interactions in human apolipoprotein E (apoE), a multi-domain, 299
      residues alpha-helical protein, on-column expressed protein ligation was utilized
      to generate a segmental-labeled apoE samples in which the N-terminal (NT-) domain
      was (2)H(99%)/(15)N-labeled whereas the C-terminal (CT-) domain was either (15)N-
      or (15)N/(13)C-labeled. 3-D (15)N-edited NOESY spectra of these segmental-labeled
      apoE samples allow for direct observation of the inter-domain NOEs between the
      backbone amide protons of the NT-domain and the aliphatic protons of the CT
      domain. This straightforward approach permits unambiguous identification of 78
      inter-domain NOEs, enabling accurate definition of the relative positions of both
      the NT- and the CT-domains and determination of the NMR structure of apoE.

PMID- 21732210
TI  - Olfactory detection thresholds and adaptation in adults with autism spectrum
      condition.
AB  - Sensory issues have been widely reported in Autism Spectrum Conditions (ASC).
      Since olfaction is one of the least investigated senses in ASC, the current
      studies explore olfactory detection thresholds and adaptation to olfactory
      stimuli in adults with ASC. 80 participants took part, 38 (18 females, 20 males)
      with ASC and 42 control participants (20 males, 22 females). A subgroup of
      participants (N = 19 in each group) also conducted an adaptation task.
      Standardized "Sniffin' Sticks" were used to measure olfactory detection levels
      and adaptation. Adults with and without ASC showed similar olfactory detection
      thresholds, and similar adaptation to an olfactory stimulus. Since diminished
      adaptation in ASC has been previously suggested, future research needs to examine
      adaptation in other modalities as well.

PMID- 21732211
TI  - Telephone counseling for patients with chronic heart failure: results of an
      evaluation study.
AB  - BACKGROUND: The effectiveness of a secondary prevention program for patients
      suffering from chronic heart failure (CHF) was evaluated. PURPOSE: The program
      aimed at improving participants' perceived health and actual physical symptoms.
      Insurants of a German health insurance company participated in a telephone
      counseling program with four modules focusing on dietary habits, physical
      activity, fluid intake, and medication compliance. METHOD: Multilevel analyses
      were conducted to analyze changes in health related outcome variables over time
      in N = 259 participants who completed the program in about 6 months. RESULTS: The
      results showed an improvement of perceived health status, physical symptoms, and
      somatic impairment. Furthermore, differential change was found when comparing
      "finishers" compared to "non-finishers" of specific modules indicating specific
      module effects. CONCLUSION: The results are auspicious and, if sustained, are
      expected to bring about long-term health benefits for our study's participants.
      The program proved to be applicable and well accepted in the sample of older,
      severely impaired CHF patients and effective in changing perceived health.

PMID- 21732212
TI  - Self-weighing frequency is associated with weight gain prevention over 2 years
      among working adults.
AB  - BACKGROUND: Little is known about the association between self-weighing frequency
      and weight gain prevention, particularly in worksite populations. PURPOSE: The
      degree to which self-weighing frequency predicted 2-year body weight change in
      working adults was examined. METHOD: The association between self-weighing
      frequency (monthly or less, weekly, daily, or more) and 24-month weight change
      was analyzed in a prospective cohort analysis (n = 1,222) as part of the larger
      HealthWorks trial. RESULTS: There was a significant interaction between follow-up
      self-weighing frequency and baseline body mass index. The difference in weight
      change ranged from -4.4 +/- 0.8 kg weight loss among obese daily self-weighers to
      2.1 +/- 0.4 kg weight gain for participants at a healthy weight who reported
      monthly self-weighing. CONCLUSION: More frequent self-weighing seemed to be most
      beneficial for obese individuals. These findings may aid in the refinement of
      self-weighing frequency recommendations used in the context of weight management
      interventions.

PMID- 21732213
TI  - The behavioral economics and neuroeconomics of reinforcer pathologies:
      implications for etiology and treatment of addiction.
AB  - The current paper presents a novel approach to understanding and treating
      addiction. Drawing from work in behavioral economics and developments in the new
      field of neuroeconomics, we describe addiction as pathological patterns of
      responding resulting from the persistently high valuation of a reinforcer and/or
      an excessive preference for the immediate consumption of that reinforcer. We
      further suggest that, as indicated by the competing neurobehavioral decision
      systems theory, these patterns of pathological choice and consumption result from
      an imbalance between two distinct neurobehavioral systems. Specifically,
      pathological patterns of responding result from hyperactivity in the
      evolutionarily older impulsive system (which values immediate and low-cost
      reinforcers) and/or hypoactivity in the more recently evolved executive system
      (which is involved in the valuation of delayed reinforcers). This approach is
      then used to explain five phenomena that we believe any adequate theory of
      addiction must address.

PMID- 21732214
TI  - Amadori-glycated phosphatidylethanolamine, a potential marker for hyperglycemia,
      in streptozotocin-induced diabetic rats.
AB  - It has been demonstrated in vivo that lipid glycation products such as Amadori
      glycated phosphatidylethanolamine (Amadori-PE) accumulate in the plasma of
      diabetic humans and animals, but how lipid glycation products are formed under
      hyperglycemic conditions are not clear. We sought to clarify the occurrence of
      lipid glycation and its relationships with lipid peroxidation and protein
      glycation during the development of hyperglycemia using the streptozotocin (STZ)
      induced diabetic rat model. A significant increase in Amadori-PE was observed in
      STZ rats 7 days after STZ treatment, and Amadori-PE (especially 18:0-20:4 Amadori
      PE) was found at high levels in the blood and in organs that are strongly
      affected by diabetes, such as the kidney. Significant changes in Amadori-PE
      appeared to occur prior to changes in levels of oxidized lipids, which increased
      after 21-28 days. In addition, accumulation of Nepsilon-(carboxymethyl)lysine
      (CML), a protein glycation product, proceeded somewhat more slowly and moderately
      than that of Amadori-PE, suggesting that Amadori-PE and CML are early and
      advanced glycation products, respectively. Our results suggest that Amadori-PE
      may be a useful predictive marker for hyperglycemia, particularly in the early
      stages of diabetes. Similar speculations have been made from previous human
      studies, but this study provides a direct evidence to support the speculations in
      rat study.

PMID- 21732215
TI  - Isolation of a novel oil globule protein from the green alga Haematococcus
      pluvialis (Chlorophyceae).
AB  - Cytoplasmic oil globules of Haematococcus pluvialis (Chlorophyceae) were isolated
      and analyzed for pigments, lipids and proteins. Astaxanthin appeared to be the
      only pigment deposited in the globules. Triacyglycerols were the main lipids
      (more than 90% of total fatty acids) in both the cell-free extract and in the oil
      globules. Lipid profile analysis of the oil globules showed that relative to the
      cell-free extract, they were enriched with extraplastidial lipids. A fatty acids
      profile revealed that the major fatty acids in the isolated globules were oleic
      acid (18:1) and linoleic acid (18:2). Protein extracts from the globules revealed
      seven enriched protein bands, all of which were possible globule-associated
      proteins. A major 33-kDa globule protein was partially sequenced by MS/MS
      analysis, and degenerate DNA primers were prepared and utilized to clone its
      encoding gene from cDNA extracted from cells grown in a nitrogen depleted medium
      under high light. The sequence of this 275-amino acid protein, termed the
      Haematococcus Oil Globule Protein (HOGP), revealed partial homology with a
      Chlamydomonas reinhardtii oil globule protein and with undefined proteins from
      other green algae. The HOGP transcript was barely detectable in vegetative cells,
      but its level increased by more than 100 fold within 12 h of exposure to nitrogen
      depletion/high light conditions, which induced oil accumulation. HOGP is the
      first oil-globule-associated protein to be identified in H. pluvialis, and it is
      a member of a novel gene family that may be unique to green microalgae.

PMID- 21732216
TI  - A rare presentation of an uncommon malignancy: thromboembolism in a patient with
      a gastrointestinal stromal tumor.

PMID- 21732217
TI  - Novel nonsense CDC73 mutations in Chinese patients with parathyroid tumors.
AB  - Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease
      characterized by the occurrences of parathyroid tumors and ossifying fibroma of
      maxilla/mandible. It is caused by mutations in CDC73 gene and mutation carriers
      are at increased risk of parathyroid carcinoma. Hyperparathyroidism could be the
      sole manifestation. We reported two Chinese patients having parathyroid neoplasm
      with equivocal malignant potential and parathyroid carcinoma respectively with
      both germline and somatic CDC73 mutations detected. Both of them presented with
      severe hypercalcemia and primary hyperparathyroidism with no other HPT-JT
      associated tumors and negative family history. We identified one novel germline
      mutation CDC73 NM_024529.4: c.1475G > A; NP_078805.3: p.Trp492X and one novel
      somatic mutation CDC73 NM_024529.4: c.142G > T; NP_078805.3: p.Glu48X. The other
      germline mutation CDC73 NM_024529.4: c.226C > T; NP_078805.3: p.Arg76X and
      somatic mutation CDC73 NM_024529.4: c.85delG; NP_078805.3: p.Glu29SerfsX8 were
      previously reported. This is the first report of CDC73 mutations in the Chinese
      population. Genetic analysis is reliable to confirm the underlying hereditary
      basis of hyperparathyroidism. By identification of mutations, the patient and the
      family members could benefit from regular surveillance for early detection of
      tumors.

PMID- 21732218
TI  - Estrogen replacement therapy and cognitive functions in healthy postmenopausal
      women: a randomized trial.
AB  - This study aimed to evaluate the effect of estrogen replacement therapy on verbal
      cognitive performance of middle-aged postmenopausal women. Middle-aged (40 to 59
      years) hysterectomized, oligosymptomatic women receiving 0.625 mg/day of
      conjugated equine estrogens (N = 27) or placebo (N = 32) in a double-blind
      parallel group design were compared according to their performance on a verbal
      memory battery before and after six 28-day cycles of treatment. Both groups had
      similar age and educational level. The estrogen group performed better on digit
      span-forward and on the recall of the easy stimuli on the verbal-paired
      associates test regardless of age, education, physical symptoms, number of years
      of menopause, or blood estradiol levels. However, the small magnitude of
      difference in the effect on attentional span suggests that the estrogen-related
      improvement is unlikely to be of clinical relevance. Estrogen replacement therapy
      did not improve verbal memory in middle-aged, hysterectomized, postmenopausal,
      asymptomatic women.

PMID- 21732219
TI  - Association between incident and baseline vertebral fractures in European women:
      vertebral fracture assessment in the Osteoporosis and Ultrasound Study (OPUS).
AB  - Vertebral fracture assessment (VFA) with densitometric devices uses less
      radiation than spinal radiography. We assessed risk of new vertebral fracture
      (VF) in women with baseline fracture identified on VFA using algorithm-based
      qualitative diagnosis. Women with VF had significantly greater risk of VF after 6
      years compared to those without baseline fracture. INTRODUCTION: Prevalent VFs
      predict future fracture and are identifiable on vertebral fracture assessment
      (VFA) using bone densitometry devices. We have previously performed cross
      sectional, but not longitudinal, VFA using the algorithm-based qualitative method
      (ABQ). We aimed to examine the prevalence and incidence of VF and test the
      association between prevalent and incident VF identified by ABQ VFA. METHODS: We
      used ABQ to assess vertebral images obtained at baseline and 6 years (Hologic
      devices) in 674 women at ages 39 to 80 years participating in the Osteoporosis
      and Ultrasound Study. Criteria for prevalent and incident VF were endplate
      fracture, with/without cortical fracture. We compared proportions (chi-squared
      test) and characteristics (two-sample t tests and analysis of variance) of women
      with and without VF and calculated odds ratios for incident VF in women with
      prevalent VF (logistic regression). RESULTS: Prevalent VF was identified in one
      premenopausal woman and 41 postmenopausal women. Incident VF was identified in 18
      postmenopausal women. Odds ratios (95% CI) for incident VF in postmenopausal
      women with prevalent VF were 7.8 (2.8, 22.1) (unadjusted) and 4.3 (1.4, 13.7)
      (adjusted for age and bone mineral density, BMD). Women with prevalent or
      incident VF were older (P < 0.01), with lower hip BMD (P < 0.001) compared to
      women without VF. CONCLUSIONS: Population-based postmenopausal women had
      relatively low prevalence and incidence of VF analysed with the ABQ method
      applied to VFA. Women with prevalent fracture had a significantly greater risk of
      incident VF than women without prevalent fracture.

PMID- 21732220
TI  - Characterization of microchannels created by metal microneedles: formation and
      closure.
AB  - Transdermal delivery of therapeutic agents for cosmetic therapy is limited to
      small and lipophilic molecules by the stratum corneum barrier. Microneedle
      technology overcomes this barrier and offers a minimally invasive and painless
      route of administration. DermaRoller((r)), a commercially available handheld
      device, has metal microneedles embedded on its surface which offers a means of
      microporation. We have characterized the microneedles and the microchannels
      created by these microneedles in a hairless rat model, using models with 370 and
      770 MUm long microneedles. Scanning electron microscopy was employed to study the
      geometry and dimensions of the metal microneedles. Dye binding studies,
      histological sectioning, and confocal microscopy were performed to characterize
      the created microchannels. Recovery of skin barrier function after poration was
      studied via transepidermal water loss (TEWL) measurements, and direct observation
      of the pore closure process was investigated via calcein imaging.
      Characterization studies indicate that 770 MUm long metal microneedles with an
      average base width of 140 MUm and a sharp tip with a radius of 4 MUm effectively
      created microchannels in the skin with an average depth of 152.5 +/- 9.6 MUm and
      a surface diameter of 70.7 +/- 9.9 MUm. TEWL measurements indicated that skin
      regains it barrier function around 4 to 5 h after poration, for both 370 and 770
      MUm microneedles. However, direct observation of pore closure, by calcein
      imaging, indicated that pores closed by 12 h for 370 MUm microneedles and by 18 h
      for 770 MUm microneedles. Pore closure can be further delayed significantly under
      occluded conditions.

PMID- 21732221
TI  - Measuring femoral lesions despite CT metal artefacts: a cadaveric study.
AB  - OBJECTIVE: Computed tomography is the modality of choice for measuring osteolysis
      but suffers from metal-induced artefacts obscuring periprosthetic tissues.
      Previous papers on metal artefact reduction (MAR) show qualitative improvements,
      but their algorithms have not found acceptance for clinical applications. We
      investigated to what extent metal artefacts interfere with the segmentation of
      lesions adjacent to a metal femoral implant and whether metal artefact reduction
      improves the manual segmentation of such lesions. MATERIALS AND METHODS: We
      manually created 27 periprosthetic lesions in 10 human cadaver femora. We filled
      the lesions with a fibrotic interface tissue substitute. Each femur was fitted
      with a polished tapered cobalt-chrome prosthesis and imaged twice--once with the
      metal, and once with a substitute resin prosthesis inserted. Metal-affected CTs
      were processed using standard back-projection as well as projection interpolation
      (PI) MAR. Two experienced users segmented all lesions and compared segmentation
      accuracy. RESULTS: We achieved accurate delineation of periprosthetic lesions in
      the metal-free images. The presence of a metal implant led us to underestimate
      lesion volume and introduced geometrical errors in segmentation boundaries.
      Although PI MAR reduced streak artefacts, it led to greater underestimation of
      lesion volume and greater geometrical errors than without its application.
      CONCLUSION: CT metal artefacts impair image segmentation. PI MAR can improve
      subjective image appearance but causes loss of detail and lower image contrast
      adjacent to prostheses. Our experiments showed that PI MAR is counterproductive
      for manual segmentation of periprosthetic lesions and should be used with care.

PMID- 21732222
TI  - Longer length of stay is not associated with better outcomes in VHA's substance
      abuse residential rehabilitation treatment programs.
AB  - Are longer stays in Veterans Health Administration (VHA) substance abuse
      residential rehabilitation treatment programs (SARRTPs) associated with better
      substance-related outcomes? To investigate, up to 50 new patients were randomly
      selected from each of 28 randomly selected programs (1,307 patients). The goal
      was to examine if patient and program average length of stay (ALOS) were
      associated with improvement on Addiction Severity Index (ASI) Alcohol and Drug
      composite scores in covariate-adjusted, multi-level regression models. Patients
      in programs with ALOS greater than 90 days tended to have more mental health
      treatment prior to the index episode and less severe substance-related symptoms,
      but more homelessness. At follow-up, programs longer than 90 days had the least
      improvement in the ASI Alcohol composite and significantly less improvement than
      programs with ALOSs of 15 to 30 and 31 to 45 days (both p < 0.05). Therefore, in
      VHA SARRTPs, ALOS greater than 90 days cannot be justified by the substance use
      disorder severity of the patients served or the magnitude of the clinical
      improvement observed.

PMID- 21732223
TI  - Nonmonotone backward masking functions and brightness reversals.
AB  - Increasing the target-field luminance aids detection for a simultaneously
      presented black target disc and a black masking annulus. At an intermediate
      interval separating the onset of the target from the mask, increasing the target
      field luminance reduces target detection. This decrease in performance occurs
      with both temporal and spatial forced choice tasks. With a spatial forced choice,
      an observer's performance can fall below chance. We associate below-chance
      performance with a brightness reversal of the black target disc, such that the
      target disc appears brighter than its surround. The occurrence of brightness
      reversals follows from our model of the Broca-Sulzer effect, and nonmonotone
      masking functions result from a generalization of luminance summation.

PMID- 21732224
TI  - Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer.
AB  - Microsatellite instability (MSI) is caused by defective mismatch repair (MMR) and
      is one of the very few molecular markers with proven clinical importance in
      colorectal cancer with respect to heredity, prognosis, and treatment effect. The
      gene expression of the MMR gene MSH2 may be a quantitative marker for the level
      of MMR and a potential molecular marker with clinical relevance. The aim was to
      investigate the gene expression of MSH2 in primary operable colorectal cancer in
      correlation with MSI, protein expression, and promoter hypermethylation. In a
      cohort of 210 patients, the primary tumor and lymphnode metastases were analyzed
      with immunohistochemistry, methylation and MSI analyses, and quantitative
      polymerase chain reaction (PCR). The median gene expression of MSH2 was 1.00
      (range 0.16-11.2, quartiles 0.70-1.51) and there was good agreement between the
      gene expression in primary tumor and lymph node metastasis (Spearman's rho =
      0.57, p < 0.001, n = 73). The validity of gene expression analysis was made
      probable by a significant correlation to protein expression (p = 0.005). MSI was
      most often caused by deficient MLH1 and was not correlated to MSH2 expression.
      Hypermethylation of the MSH2 gene promoter was only detected in 14 samples and
      only at a low level with no correlation to gene expression. MSH2 gene expression
      was not a prognostic factor for overall survival in univariate or multivariate
      analysis. The gene expression of MSH2 is a potential quantitative marker ready
      for further clinical validation.

PMID- 21732225
TI  - Treatment targets in intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than
      ischemic stroke. The therapeutic interventions that are currently available focus
      mainly on supportive care and secondary prevention. There is a paucity of
      evidence to support any one acute intervention that improves functional outcome.
      This chapter highlights current treatment targets for ICH based on the
      pathophysiology of the disease.

PMID- 21732226
TI  - SPECT imaging for detecting coronary artery disease and determining prognosis by
      noninvasive assessment of myocardial perfusion and myocardial viability.
AB  - Basic knowledge of active and passive transport mechanisms for concentrating
      monovalent cations in myocardial cells led to the investigation of the
      application of radioisotopes of potassium, thallium, rubidium, and ammonia to the
      in vivo noninvasive assessment of regional myocardial perfusion and viability
      utilizing gamma camera or positron emission tomographic (PET) imaging technology.
      Subsequently, technetium-99m (Tc-99m)-labeled isonitriles (sestamibi and
      tetrofosmin), which bind to mitochondrial membranes, emerged as superior imaging
      agents with single photon emission tomography (SPECT) imaging. When any of these
      imaging agents are injected intravenously during either exercise or pharmacologic
      stress, myocardial defects in tracer uptake represent either abnormal regional
      flow reserve or myocardial scar reflecting of coronary artery disease (CAD). The
      major clinical indications for stress SPECT or PET myocardial perfusion imaging
      are for detection of CAD as the cause of chest pain and risk stratification for
      prognostication. Patients with normal stress myocardial perfusion scans have an
      excellent prognosis with <1.0% annual rate future annual death or nonfatal
      infarction. The greater the extent and severity of ischemic perfusion defects
      (defects seen on stress images but improve on resting images), the greater the
      subsequent death or infarction rate during follow-up. Rest imaging alone is
      performed for determination of myocardial viability in patients with CAD and
      severe left ventricular dysfunction. Myocardial segments showing >50% uptake
      compared to normal uptake have a better long-term outcome with revascularization
      than with medical therapy with enhanced left ventricular function and improved
      survival. Other applications of SPECT imaging include the evaluation of cardiac
      sympathetic function, assessment of myocardial metabolism in health and disease,
      and molecular imaging of coronary atherosclerosis and myocardial stem cell
      therapy.

PMID- 21732227
TI  - Physical and mental health status and health behaviors of survivors of multiple
      cancers: a national, population-based study.
AB  - BACKGROUND: Little is known about the unique experience of adults with a history
      of multiple cancer diagnoses (i.e., survivors of multiple cancers). PURPOSE: This
      research assessed the health status and health behaviors of survivors of multiple
      cancers. METHODS: The health status and health behaviors of 8,734 survivors of
      multiple cancers, 47,562 survivors of a single cancer, and 348,229 non-cancer
      controls were compared using weighted data from the 2009 Behavioral Risk Factor
      Surveillance System. RESULTS: Survivors of multiple cancers reported poorer
      physical and mental health status outcomes (e.g., more mental distress and
      greater activity limitations) than survivors of a single cancer (all p's < 0.001)
      who reported poorer outcomes than controls (all p's < 0.001). Survivors of
      multiple cancers reported unhealthier behaviors than survivors of a single cancer
      and healthier behaviors than controls on most health behavior outcomes (e.g.,
      alcohol use, tobacco use, and diet) (all p's < 0.001). CONCLUSIONS: Data suggest
      the need for clinical interventions to enhance physical and mental health status
      and to increase adoption of healthier behaviors in survivors of multiple cancers.

PMID- 21732228
TI  - Utility of high fat and low carbohydrate diet in suppressing myocardial FDG
      uptake.
AB  - INTRODUCTION: Fluoro-deoxy-glucose (FDG) can be used to visualize inflammation in
      atherosclerotic plaques in coronary arteries, if myocardial FDG uptake is
      adequately suppressed. Prolonged fasting for suppressing myocardial FDG uptake is
      inconsistent. We evaluated the feasibility to consistently suppress myocardial
      FDG uptake with a low carbohydrate high fat protein permitted (LCHFPP) diet.
      MATERIALS AND METHODS: This was a prospective study. 50 patients were included in
      fasting group (>12 hours fasting) and 60 patients were included into LCHFPP diet.
      Fasting group had no special dietary preparation. Patients in LCHFPP diet group
      were asked to consume LCHFPP diet the night before and 4 hours prior to the
      study. Visual analysis of myocardial FDG uptake was done on maximum intensity
      projection image. Using CT images for localization, the ability to delineate
      possible FDG uptake in the left coronary artery was assessed in the corresponding
      PET image and the studies were classified as "interpretable" or "Not
      interpretable". RESULTS: 60 patients (mean age 47 years) from LCHFPP diet group
      and 50 patients (mean age 49.9 years) from fasting group were included. None of
      the patients were known diabetics. The mean blood glucose level was 96 mg/dL.
      Forty-eight patients had consumed LCHFPP diet as per protocol. Twelve had
      consumed LCHFPP diet only on the night before the study (non-compliant). The
      average duration of fasting in compliant patients was 5.9 +/- 0.9 hours in the
      diet group and 14.6 hours in fasting group. In LCHFPP diet group, the myocardial
      FDG uptake was classified as complete suppression in 31; minimal uptake in 15;
      moderate inhomogenous uptake in 8 and homogenous intense uptake in 6 patients.
      Fifty-four of the 60 patients had interpretable study. When non-compliant
      patients were excluded, 84% of the patients had significant FDG uptake
      suppression and 94% of the studies were classified as interpretable. In the
      fasting group, complete myocardial suppression of FDG uptake was noticed in 16;
      minimal in 8; moderate inhomogenous in 15; and homogenous intense in 11 patients.
      27 patients (54%) had interpretable study. CONCLUSION: Consistent and significant
      myocardial FDG uptake suppression is possible in most patients using LCHFPP diet.
      The LCHFPP diet, if taken as per protocol, leads to consistent myocardial FDG
      uptake suppression to allow for adequate evaluation of the left coronary artery
      inflammation in nearly all the patients. LCHFPP diet is also significantly more
      efficacious than prolonged (>12 hours) fasting protocol in suppressing myocardial
      FDG uptake.

PMID- 21732229
TI  - A preclinical study of the safety and efficacy of OcclusinTM 500 Artificial
      Embolization Device in sheep.
AB  - INTRODUCTION: This study evaluated the safety, effectiveness, and biodegradation
      of a new embolic agent, OcclusinTM 503 Artificial Embolization Device (OCL 503).
      The agent consists of biodegradable poly-lactic-co-glycolic acid microspheres
      (150-212 MUm) coated with type I bovine collagen and was compared with
      Embosphere(r) Microspheres (300-500 MUm) in this controlled study of uterine
      artery embolization (UAE) in sheep. METHODS: Unilateral UAE was performed in 32
      adult ewes randomly assigned. Vessels were embolized to effective stasis. The
      cohort was divided into four groups, which were sacrificed at 1, 3, 6, and 12
      months. RESULTS: Both agents were 100% effective in achieving stasis. At 6
      months, all OCL 503-treated arteries were occluded, the microspheres degraded
      with time, and at 12 months all four animals examined demonstrated
      recanalization. OCL 503 was found in the untreated uterine artery in one animal
      with no other evidence of non target embolization. In the Embosphere-treated
      group, all vessels remained occluded and microspheres were detected in the
      contralateral uterine artery in 6 of 15 examined vessels and in 10 vaginal, 2
      ovarian, and 1 vesical artery. No procedural-related complications were seen in
      either group. CONCLUSIONS: OCL 503 is as effective an embolic agent as
      Embosphere(r) Microspheres when embolizing ovine uterine arteries and resorbs
      with time, allowing recanalization of the treated arteries. No device-related
      issues or adverse events were observed.

PMID- 21732230
TI  - Two cases of plasmacytoid variant of urothelial carcinoma of urinary bladder:
      systemic chemotherapy might be of benefit.
AB  - We report two cases of the plasmacytoid variant of urothelial carcinoma of
      urinary bladder in which systemic chemotherapy was effective. In the first case,
      a 76-year-old man presented with dysphasia. Magnetic resonance imaging (MRI) and
      computed tomography revealed a brain tumor and a bladder tumor. Resection of the
      brain tumor and transurethral resection of the bladder tumor were performed. The
      pathological diagnosis was plasmacytoid variant of urothelial carcinoma of
      urinary bladder with brain metastasis (pT1N0M1). Three cycles of adjuvant MVAC
      (methotrexate, vinblastine, adriamycin, and cisplatin) chemotherapy were
      performed. He has no evidence of recurrence 96 months after resection of brain
      metastasis. In the second case, a 76-year-old man presented with hematuria. MRI
      revealed a bladder tumor with abdominal wall invasion, and a transurethral biopsy
      was performed. The pathological diagnosis was plasmacytoid variant of urothelial
      carcinoma of urinary bladder (cT4bN0M0). After three cycles of neoadjuvant GC
      (gemcitabine and cisplatin) chemotherapy, MRI demonstrated a complete response.
      Radical cystectomy was performed, and the pathological diagnosis was pT0pN0.
      Although there was no evidence of recurrence 9 months after radical cystectomy,
      he died from other causes. Our two cases suggest that systemic chemotherapy might
      be effective for the plasmacytoid variant of urothelial carcinoma.

PMID- 21732231
TI  - Pathogenic and regulatory T cells in type 1 diabetes: losing self-control,
      restoring it, and how to take the temperature.
AB  - The central role of T cells in type 1 diabetes pathogenesis is well established,
      but these cells continue to pose numerous challenges in understanding their
      dynamics and in following their modifications. Important progress has been
      recently made in pinpointing some novel antigens targeted by pathogenic T cells
      and the epitope sequences recognized. Studies on the interplay between effector T
      cells, their regulatory counterparts, and cells of the innate immune system have
      unraveled novel pathways and may inspire new therapeutic approaches. At the same
      time, the appreciation of the plasticity of regulatory T cells has raised
      important caveats on their use for cell-based therapies. Continuous development
      of T-cell assays exploring both pathogenic and regulatory players will be
      critical to "take the temperature" of undergoing disease progression and
      reversal.

PMID- 21732232
TI  - The role of lean body mass and physical activity in bone health in children.
AB  - In the context of physical education curricula, markers of physical fitness
      (e.g., aerobic capacity, muscular strength, flexibility, and body mass index or
      body fat) are usually evaluated in reference to health standards. Despite their
      possible mediating role in the relationship between weight-bearing or muscle
      forces and features of bone tissue, these attributes of fitness may not be the
      most relevant to predict skeletal health. It is therefore important to analyze
      the relative contribution of these factors to the variability in bone tissue of
      different parts of the skeleton, and to analyze it by gender, as sensitivity to
      mechanical loading can diverge for boys and girls. We compared the effects of
      habitual physical activity (PA) and lean mass, as surrogates of weight-bearing
      and muscle forces, and of physical fitness (aerobic and muscle capacity of lower
      and upper limbs) on bone mineral content (BMC) and size of total body, lumbar
      spine, femoral neck, and 1/3 radius in 53 girls and 64 boys from 7.9 to 9.7 years
      of age. After controlling for bone age, body mass, body height, and calcium
      intake, lean mass was the most important predictor of bone size and/or mineral in
      both genders (p < 0.05), while habitual weight-bearing PA positively influenced
      BMC in boys (p < 0.05). The effect of muscle in bone was not determined by PA and
      fitness score did not explain bone variability. Femoral neck was the bone site
      more closely associated with mechanical loading factors; boys with a PA > 608
      counts/min/day (~105 min/day of moderate and vigorous intensity) showed 13-20%
      more BMC than those with less physical activity, and girls with a lean mass >19
      kg showed 12-19% more BMC than those with less lean mass. These findings suggest
      that lean mass was the most important predictor of bone size and/or
      mineralization in both genders, while habitual weight-bearing PA appears to
      positively impact on bone mineral in prepubertal boys and that both lean mass and
      PA need to be considered in physical education curricula and other health
      enhancing programs.

PMID- 21732233
TI  - [Endoprosthetics].

PMID- 21732234
TI  - [Musculoskeletal puncture, injection and infiltration: swiss rheumatologists'
      point of view].
AB  - Arthrocentesis, injection and infiltration of joints and soft tissues belong to
      the basic procedures in rheumatology. The indications and the practical
      performance are based on experience and tradition. Nowadays, a crucial
      reappraisal and adaption of indications and technical aspects appear important in
      the light of new evidence and technical developments. The main indications for
      puncture remain the search of an infectious arthritis and reduction of intra
      articular pressure due to effusion. Good indications for the injection of
      glucocorticoids are inflammation in sterile joints and activated osteoarthritis.
      The local infiltration with corticosteroids in mechanically induced
      enthesopathies at the lateral epicondyle of the humerus or at the plantar fascia
      have to be questioned in the light of recent publications which show that this
      common practice is associated with a poorer outcome than without injection.

PMID- 21732235
TI  - [Report of the DGRh (German Society for Rheumatology)].

PMID- 21732236
TI  - [Report of the DRL].

PMID- 21732237
TI  - Shock, adjust, decide: reproductive decision making in cystic fibrosis (CF)
      carrier couples--a qualitative study.
AB  - Cystic fibrosis (CF) is the most common recessive condition affecting the White
      British population. Facilitating reproductive decision making for couples at
      genetic risk for CF is an important aspect of genetic counseling practice in the
      UK. The purpose of this study was to explore the reproductive decision making
      process for 31 members of CF carrier couples (15 men and 16 women) with or
      without an affected child. The design involved a qualitative approach consisting
      of semi-structured interviews and data analysis informed by grounded theory
      methodology. Sex and personal experience of CF were identified as factors that
      may influence reproductive decision making. Findings suggest these hypotheses:
      (1) CF carrier couples who have an affected child/pregnancy, are more likely to
      embark on another pregnancy than couples who have a healthy child from an at-risk
      pregnancy, and (2) men and women play different roles in the reproductive
      decision making process. Data analysis resulted in development of a structured
      framework modeling the reproductive decision making process, which may be helpful
      in guiding genetic counseling with CF carrier couples and other at risk couples
      making reproductive decisions.

PMID- 21732238
TI  - Control of ADAR1 editing of hepatitis delta virus RNAs.
AB  - Hepatitis delta virus (HDV) uses ADAR1 editing of the viral antigenome RNA to
      switch from viral RNA replication to packaging. At early times in the replication
      cycle, the virus produces the protein HDAg-S, which is required for RNA
      synthesis; at later times, as result of editing at the amber/W site, the virus
      produces HDAg-L, which is required for packaging, but inhibits further RNA
      synthesis as levels increase. Control of editing during the replication cycle is
      essential for the virus and is multifaceted. Both the rate at which amber/W site
      editing occurs and the ultimate amount of editing are restricted; moreover,
      despite the nearly double stranded character of the viral RNA, efficient editing
      is restricted to the amber/W site. The mechanisms used by the virus for
      controlling editing operate at several levels, and range from molecular
      interactions to procedural. They include the placement of editing in the HDV
      replication cycle, RNA structural dynamics, and interactions of both ADAR1 and
      HDAg with specific structural features of the RNA. That HDV genotypes 1 and 3 use
      different RNA structural features for editing and control the process in ways
      related to these features underscores the critical roles of editing and its
      control in HDV replication. This review will cover the mechanisms of editing at
      the amber/W site and the means by which the virus controls it in these two
      genotypes.

PMID- 21732239
TI  - ADHD: volumetry, motor, and oculomotor functions.
AB  - The use of quantitative neuroimaging (volumetry), motor, and oculomotor
      assessments for studying children with attention-deficit/hyperactivity disorder
      (ADHD) has grown dramatically in the past 20 years. Most evidence to date
      suggests that anomalous basal ganglia development plays an important role in
      early manifestation of ADHD; however, widespread cerebellar and cortical delays
      are also observed and are associated with the behavioral (cognitive, motor,
      oculomotor) phenotype in children with ADHD. These motor and "executive" control
      systems appear to develop in parallel, such that both systems display a similar
      protracted developmental trajectory, with periods of rapid growth in elementary
      years and continued maturation into young adulthood. Development of each system
      is dependent on the functional integrity and maturation of related brain regions,
      suggesting a shared neural circuitry that includes frontostriatal systems and the
      cerebellum (i.e., those identified as anomalous in studies of volumetry in ADHD).
      Motor and oculomotor paradigms provide unique opportunities to examine executive
      control processes that exist at the interface between movement and cognition in
      children with ADHD, also linking cognition and neurological development. The
      observed pattern of volumetric differences, together with the known parallel
      development of motor and executive control systems, appears to predict motor and
      oculomotor anomalies in ADHD, which are highly relevant, yet commonly overlooked
      in clinical settings.

PMID- 21732240
TI  - Metabolic engineering of flavonoids in plants and microorganisms.
AB  - Over 9,000 flavonoid compounds have been found in various plants, comprising one
      of the largest families of natural products. Flavonoids are an essential factor
      in plant interactions with the environment, often serving as the first line of
      defense against UV irradiation and pathogen attacks. Flavonoids are also major
      nutritional compounds in foods and beverages, with demonstrated health benefits.
      Some flavonoids are potent antioxidants, and specific flavonoid compounds are
      beneficial in many physiological and pharmacological processes. Therefore,
      engineering of flavonoid biosynthesis in plants or in microorganisms has
      significant scientific and economical importance. Construction of biosynthetic
      pathways in heterologous systems offers promising results for large-scale
      flavonoid production by fermentation or bioconversion. Genomics and metabolomics
      now offer unprecedented tools for detailed understanding of the engineered
      transgenic organism and for developing novel technologies to further increase
      flavonoid production yields. We summarize some of the recent metabolic
      engineering strategies in plants and microorganisms, with a focus on applications
      of metabolic flux analysis. We are confident that these engineering approaches
      will lead to successful industrial flavonoid production in the near future.

PMID- 21732241
TI  - Isolation of a novel promoter for efficient protein expression by Aspergillus
      oryzae in solid-state culture.
AB  - A novel promoter from a hemolysin-like protein encoding the gene, hlyA, was
      characterized for protein overexpression in Aspergillus oryzae grown in solid
      state culture. Using endo-1,4-beta-glucanase from A. oryzae (CelA) as the
      reporter, promoter activity was found to be higher than that of the alpha-amylase
      (amyA) and manganese superoxide dismutase (sodM) genes not only in wheat bran
      solid-state culture but also in liquid culture. Expression of the A. oryzae
      endoglucanase CelB and two heterologous endoglucanases (TrEglI and TrEglIII from
      Trichoderma reesei) under the control of the hlyA promoter were also found to be
      stronger than under the control of the amyA promoter in A. oryzae grown in wheat
      bran solid-state culture, suggesting that the hlyA promoter may be useful for the
      overproduction of other proteins as well. In wheat bran solid-state culture, the
      productivity of the hlyA promoter in terms of protein produced was high when the
      cultivation temperature was 30 degrees C or 37 degrees C, when the water content
      was 0.6 or 0.8 ml/g wheat bran, and from 48 to 72 h after inoculation. Because A.
      oryzae sporulated actively under these conditions and because hemolysin has been
      reported to play a role in fungal fruiting body formation, high-level expression
      of hlyA may be related to sporulation.

PMID- 21732242
TI  - Alkanols and chlorophenols cause different physiological adaptive responses on
      the level of cell surface properties and membrane vesicle formation in
      Pseudomonas putida DOT-T1E.
AB  - In order to cope with the toxicity imposed by the exposure to environmental
      hydrocarbons, many bacteria have developed specific adaptive responses such as
      modifications in the cell envelope. Here we compared the influence of n-alkanols
      and chlorophenols on the surface properties of the solvent-tolerant bacterium
      Pseudomonas putida DOT-T1E. In the presence of toxic concentrations of n
      alkanols, this strain significantly increased its cell surface charge and
      hydrophobicity with changes depending on the chain length of the added n
      alkanols. The adaptive response occurred within 10 min after the addition of the
      solvent and was demonstrated to be of physiological nature. Contrary to that,
      chlorophenols of similar hydrophobicity and potential toxicity as the
      corresponding alkanols caused only minor effects in the surface properties. To
      our knowledge, this is the first observation of differences in the cellular
      adaptive response of bacteria to compound classes of quasi equal hydrophobicity
      and toxicity. The observed adaptation of the physico-chemical surface properties
      of strain DOT-T1E to the presence of alkanols was reversible and correlated with
      changes in the composition of the lipopolysaccharide content of the cells. The
      reaction is explained by previously described reactions allowing the release of
      membrane vesicles that was demonstrated for cells affected by 1-octanol and heat
      shock, whereas no membrane vesicles were released after the addition of
      chlorophenols.

PMID- 21732243
TI  - Sulfhydryl oxidases: sources, properties, production and applications.
AB  - The formation of disulfide bonds in proteins and small molecules can greatly
      affect their functionality. Sulfhydryl oxidases (SOXs) are enzymes capable of
      oxidising the free sulfhydryl groups in proteins and thiol-containing small
      molecules by using molecular oxygen as an electron acceptor. SOXs have been
      isolated from the intracellular compartments of many organisms, but also secreted
      SOXs are known. These latter enzymes are generally active on small compounds and
      their physiological role is unknown, whereas the intracellular enzymes prefer
      proteins as substrates and are involved in protein folding. An increasing number
      of scientific publications and patent applications on SOXs have been published in
      recent years. The present mini-review provides an up-to-date summary of SOXs from
      various families, their production and their actual or suggested applications.
      The sequence features and domain organisation of the characterised SOXs are
      reviewed, and special attention is paid to the physicochemical features of the
      enzymes. A review of patents and patent applications regarding this class of
      enzymes is also provided.

PMID- 21732244
TI  - Scleroglucan: biosynthesis, production and application of a versatile
      hydrocolloid.
AB  - Since its first description in the early 1960s, scleroglucan attracted much
      attention from both academia and industry. Scleroglucan is an exopolysaccharide
      secreted by the basidiomycete Sclerotium rolfsii and appreciated as a
      multipurpose compound applicable in many industrial fields, including oil
      industry, food industry and pharmacy. In this review, the current knowledge on
      scleroglucan chemistry, genetics, biosynthesis and production will be summarized
      and different application possibilities will be discussed. The biosynthesis of
      scleroglucan in S. rolfsii will be highlighted by recent transcriptomic data and
      linked to physiological data to better understand the biogenesis of scleroglucan
      and its link to the phytopathologic lifestyle of S. rolfsii.

PMID- 21732245
TI  - Enzymatic degradation of granular potato starch by Microbacterium aurum strain
      B8.A.
AB  - Microbacterium aurum strain B8.A was isolated from the sludge of a potato starch
      processing factory on the basis of its ability to use granular starch as carbon-
      and energy source. Extracellular enzymes hydrolyzing granular starch were
      detected in the growth medium of M. aurum B8.A, while the type strain M. aurum
      DSMZ 8600 produced very little amylase activity, and hence was unable to degrade
      granular starch. The strain B8.A extracellular enzyme fraction degraded wheat,
      tapioca and potato starch at 37  degrees C, well below the gelatinization
      temperature of these starches. Starch granules of potato were hydrolyzed more
      slowly than of wheat and tapioca, probably due to structural differences and/or
      surface area effects. Partial hydrolysis of starch granules by extracellular
      enzymes of strain B8.A resulted in large holes of irregular sizes in case of
      wheat and tapioca and many smaller pores of relatively homogeneous size in case
      of potato. The strain B8.A extracellular amylolytic system produced mainly
      maltotriose and maltose from both granular and soluble starch substrates; also,
      larger maltooligosaccharides were formed after growth of strain B8.A in rich
      medium. Zymogram analysis confirmed that a different set of amylolytic enzymes
      was present depending on the growth conditions of M. aurum B8.A. Some of these
      enzymes could be partly purified by binding to starch granules.

PMID- 21732246
TI  - Quantitative investigation of non-hydrolytic disruptive activity on crystalline
      cellulose and application to recombinant swollenin.
AB  - For the efficient degradation and bioconversion of cellulosic biomass, it is
      important to efficiently disrupt and convert crystalline regions of cellulose
      into easily hydrolyzable regions than to simply hydrolyze cellulose. Expansin
      like proteins such as swollenins have disruptive functions on lignocellulose,
      including crystalline cellulose, via non-hydrolytic mechanisms. In this work, we
      produced the swollenin from Trichoderma asperellum in Escherichia coli. The
      recombinant protein was then refolded into the bioactive form with simultaneous
      purification via a novel cellulose-assisted process. We devised a novel, simple,
      and efficient method to quantitatively determine the non-hydrolytic disruptive
      activity of swollenin on crystalline cellulose. This method is based on the
      synergism of the swollenin and the endoglucanase FnCel5A from Fervidobacterium
      nodosum. The change from crystalline regions into easily hydrolyzable forms, due
      to non-hydrolytic disruption, might be slight and not easily be observed.
      However, disrupted regions of cellulose could be hydrolyzed by FnCel5A, and
      reducing sugars were formed by the synergism. The disruptive function of the
      swollenin was quantitatively characterized by measuring the release of reducing
      sugars. These methods and processes will be useful for further research on non
      hydrolytic disruptive bioactivities and provide novel approaches for the
      efficient and economical bioconversion of cellulosic biomass.

PMID- 21732247
TI  - The benefits of being transient: isotope-based metabolic flux analysis at the
      short time scale.
AB  - Metabolic fluxes are the manifestations of the co-operating actions in a complex
      network of genes, transcripts, proteins, and metabolites. As a final quantitative
      endpoint of all cellular interactions, the intracellular fluxes are of immense
      interest in fundamental as well as applied research. Unlike the quantities of
      interest in most omics levels, in vivo fluxes are, however, not directly
      measureable. In the last decade, 13C-based metabolic flux analysis emerged as the
      state-of-the-art technique to infer steady-state fluxes by data from labeling
      experiments and the use of mathematical models. A very promising new area in
      systems metabolic engineering research is non-stationary 13C-metabolic flux
      analysis at metabolic steady-state conditions. Several studies have demonstrated
      an information surplus contained in transient labeling data compared to those
      taken at the isotopic equilibrium, as it is classically done. Enabled by recent,
      fairly multi-disciplinary progress, the new method opens several attractive
      options to (1) generate new insights, e.g., in cellular storage metabolism or the
      dilution of tracer by endogenous pools and (2) shift limits, inherent in the
      classical approach, towards enhanced applicability with respect to cultivation
      conditions and biological systems. We review the new developments in metabolome
      based non-stationary 13C flux analysis and outline future prospects for accurate
      in vivo flux measurement.

PMID- 21732248
TI  - A comparative study of fragment screening methods on the p38alpha kinase: new
      methods, new insights.
AB  - The stress-activated kinase p38alpha was used to evaluate a fragment-based drug
      discovery approach using the BioFocus fragment library. Compounds were screened
      by surface plasmon resonance (SPR) on a Biacore(TM) T100 against p38alpha and two
      selectivity targets. A sub-set of our library was the focus of detailed follow-up
      analyses that included hit confirmation, affinity determination on 24 confirmed,
      selective hits and competition assays of these hits with respect to a known ATP
      binding site inhibitor. In addition, functional activity against p38alpha was
      assessed in a biochemical assay using a mobility shift platform (LC3000, Caliper
      LifeSciences). A selection of fragments was also evaluated using fluorescence
      lifetime (FLEXYTE(TM)) and microscale thermophoresis (Nanotemper) technologies. A
      good correlation between the data for the different assays was found. Crystal
      structures were solved for four of the small molecules complexed to p38alpha.
      Interestingly, as determined both by X-ray analysis and SPR competition
      experiments, three of the complexes involved the fragment at the ATP binding
      site, while the fourth compound bound in a distal site that may offer potential
      as a novel drug target site. A first round of optimization around the remotely
      bound fragment has led to the identification of a series of triazole-containing
      compounds. This approach could form the basis for developing novel and active
      p38alpha inhibitors. More broadly, it illustrates the power of combining a range
      of biophysical and biochemical techniques to the discovery of fragments that
      facilitate the development of novel modulators of kinase and other drug targets.

PMID- 21732249
TI  - Fragment-based lead discovery: challenges and opportunities.
AB  - Fragment-based lead discovery has undergone remarkable changes over the last 15
      years. During this time, the pharmaceutical industry has changed dramatically as
      well, and continued evolution of the industry is assured. These changes present
      many challenges but also several opportunities for executing fragment-based drug
      design. This article will explore some of the more significant changes in the
      industry and how they may affect future discovery efforts related to fragment
      based initiatives.

PMID- 21732250
TI  - Cancer's Enemy.
AB  - The Cancer Prevention and Research Institute of Texas (CPRIT) supports cancer
      prevention and control programs, as well as research and commercialization
      projects. CPRIT funds public and professional education, clinical services, and
      policy and systems change. It is interested in supporting projects that will
      encourage real change in how physicians deliver cancer care and show a measurable
      difference at the patient level.

PMID- 21732251
TI  - Chasing dr. Feelgood.
AB  - Texas has fewer pill mills churning out massive volumes of prescriptions for
      powerful narcotics thanks to the Texas Medical Board (TMB). Since Sept. 1, 2010,
      pain management clinics must be TMB-certified to continue operating. The board
      has been busy enforcing the law. At press time, TMB had suspended 11 pain
      management clinic certificates and five physicians' medical licenses because of
      rule violations.

PMID- 21732252
TI  - Changing MCAT.
AB  - A special committee of the Association of American Medical Colleges is
      recommending major changes to the Medical College Admission Test (MCAT) to more
      closely align its subject matter with the science knowledge needed to practice
      21st century medicine. But while the proposed new MCAT increases the emphasis on
      biochemistry and cellular and molecular biology, it also sharpens the focus on
      critical analysis and behavioral and social sciences that affect the more human
      side of medicine.

PMID- 21732253
TI  - High tech u.
AB  - Implementing a certified electronic health record system and then achieving
      meaningful use are no small tasks for a medical practice. The federal government
      has made $116 million in grants available nationwide to ramp up training for a
      robust, qualified workforce to help physicians. Community colleges and
      universities throughout Texas use the federal money to enhance or create
      certificate and degree programs that will prepare medical office staff, recent
      college graduates, and information technology professionals to oversee health
      information technology at multiple sites, including the physician practice.

PMID- 21732258
TI  - [Are phyllanthus species effective in hepatitis B?].

PMID- 21732259
TI  - [Are public programs to promote physical activity effective?].

PMID- 21732260
TI  - [Comparison of survival under domestic or institutional care: the Hannover
      morbidity and mortality long-term care study].
AB  - BACKGROUND AND OBJECTIVE: Empirical data, representative of the total population
      are necessary for medico-actuarial risk calculations. Our study compares
      mortalities of long-term care (LTC) patients with regard to age, gender and
      distribution of care levels when in home or institutional care. METHODS: The data
      of 88.575 long-term care patients were analysed longitudinally for ten years,
      using routine data on the files of the German Federal Health Insurance fund
      (average observation period 2.5 years, a total of 221.625 observation years). The
      numbers of LTC patients and their care levels while remaining in home or
      institutional care were calculated, as were any changes to another care level or
      discontinuation of long-term care benefits (as a result of the need for care
      falling below the eligibility criteria for care level I or to death) during 1 -
      10 years after the onset of long-term care. RESULTS: Total mortality was found to
      increase with age and care level in homecare as well as in institutional settings
      for both sexes. It is greatly influenced by the first year mortality, which for
      both genders was lower for care level 1 in home care settings but higher for care
      level 2 and much higher for care level 3 than in institutional care settings.
      Follow-up mortality (second to tenth year after the start of LTC) was lower for
      care level 1 and 2 in home care settings than for institutional care. But for
      care level 3 the follow-up mortality was conversely higher in home care settings
      than in institutional care (for both genders). The number of patients returning
      to an active life after rehabilitation is much higher for home care patients than
      those who had been in institutional care. The transfer rate from homecare to
      institutional care increased during the first three years after onset of care,
      descending thereafter, and was much higher than conversely. CONCLUSION: The
      slogan "outpatient care before inpatient care" must be differentiated and
      considered carefully with regard to the character and constellation of diseases,
      age attained, length of time after onset of care, care level, potential for
      resuming an active life, as well as level of compensation and number and nature
      of activities of daily life together with being given the necessary help when
      choosing between homecare or institutional care. Differentiation between first
      year and follow-up mortalities is recommended when undertaking medico-actuarial
      calculations.

PMID- 21732261
TI  - [Inferior vena cava thrombosis after laparoscopy].
AB  - HISTORY AND FINDINGS: A previously healthy 43-year-old woman was admitted because
      of pain in the lower abdomen. Abdominal and transvaginal ultrasound revealed a
      cystic structure in the right ovary, providing the indication for an exploratory
      laparoscopy. A hemorrhagic corpus luteum was enucleated. Laboratory tests had
      merely shown a raised C-reactive protein level and marginally elevated
      leukocytes. A family history of thrombotic episodes had been elicited. FURTHER
      COURSE, DIAGNOSIS AND TREATMENT: Although heparin had been applied increasing
      swelling developed in both thighs and lower legs at day six, indicating
      thrombosis of the inferior vena cava. Laboratory tests revealed a mutation in
      factor V (Leiden). Computed tomography showed complete thrombotic IVC occlusion.
      Thrombolytic treatment with recombinant tissue plasminogen was initiated, direct
      thrombus aspiration attempted and a filter inserted in the IVC. Low molecular
      heparin was infused, replaced by oral anticoagulation with phenprocoumon.
      Subsequent Doppler ultrasound examination demonstrated almost complete resolution
      of the thrombus, except for a few small residual thrombi. CONCLUSION: This case
      demonstrates that even minor laparoscopic interventions carry the risk of an IVC
      thrombosis as a late complication, indicating appropriate measures to prevent
      thrombosis.

PMID- 21732262
TI  - [New options for helicobacter pylori antibiotic treatment].
AB  - Helicobacter plays a central role in the pathogenesis of several gastric diseases
      and its eradication has a therapeutic or prophylactic effect in many clinical
      situations. However, treatment of Helicobacter infection can be challenging and
      the frequently recommended clarithromycin based triple therapy fails in more than
      20% of patients. Reasons for treatment failure include antibiotic resistances and
      bacterial persistence in an acidic stomach, for instance due to rapid
      metabolization of the proton pump inhibitor by the host. Therapeutic efficiency
      can be improved by a therapy tailored for an individual patient and the
      respective pathogen. In an alternative approach the antibiotic therapy can be
      intensified leading to a sequential or concomitant therapy. These and other
      strategies tested only in single studies can achieve eradication in 90 % and up
      to over 95 % of patients, respectively, and should be used more often in clinical
      practice.

PMID- 21732263
TI  - [Treatment of pseudoaneurysms by thrombin injection].
AB  - The incidence of pseudoaneurysms after percutaneus arterial procedures is a quite
      common complication. Ultrasound-guided thrombin injection is an effective and
      elegant therapy with a low procedural risk, when the physician is trained in the
      technique. This paper provides a tutorial for physicians including tips and
      pitfalls.

PMID- 21732264
TI  - [Effectiveness, quality and transfer: further development of disease prevention
      and health promotion through research].

PMID- 21732266
TI  - [Improving general practitioners guided dementia care].

PMID- 21732267
TI  - [IgG food allergies - a subject of controversy].

PMID- 21732270
TI  - The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging
      and narrow-band imaging for differentially diagnosing colon adenoma.
AB  - BACKGROUND AND STUDY AIMS: Conventional colonoscopy can result in unnecessary
      biopsy or endoscopic resection due to its inability to distinguish adenomas from
      hyperplastic polyps. This study therefore evaluated the efficacy of high
      resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band
      imaging (NBI) in discriminating colon adenoma from hyperplastic polyps. PATIENTS
      AND METHODS: This was a prospective multicenter study in patients undergoing AFI
      and NBI examinations. HRE, AFI, and NBI images were classified into two groups
      based on morphological characteristics, the predominant color intensities, and
      the visibility of meshed capillary vessels, respectively. Each of the endoscopic
      photographs were independently evaluated by a single endoscopist. The images were
      then assessed by three specialists and three residents, the latter having
      performed < 500 colonoscopies and < 30 NBI and AFI examinations. Diagnostic test
      statistics were calculated to compare the accuracy in differentiating colon
      adenoma from hyperplastic polyps for each method. RESULTS: A total of 183
      patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps
      were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps
      with an accuracy of 84.9 % and 88.4 %, respectively, whereas HRE exhibited an
      accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent
      with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9
      %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and
      residents, AFI and NBI dramatically improved the diagnostic accuracy of residents
      from 69.1 % to 86.1 % and 84.7 %, respectively. CONCLUSIONS: Both AFI and NBI are
      considered to be feasible tools that can discriminate colon adenoma from
      hyperplastic polyps, and their use may be particularly beneficial for less
      experienced endoscopists.

PMID- 21732271
TI  - Natural-orifice transluminal endoscopic surgery: low-pressure pneumoperitoneum is
      sufficient and is associated with an improved cardiopulmonary response
      (PressurePig Study).
AB  - BACKGROUND AND AIMS: The aim of this randomized trial in the acute porcine model
      was to compare the quality of transgastric peritoneoscopy with the use of low
      pressure versus standard-pressure pneumoperitoneum and to evaluate the respective
      associated cardiopulmonary changes. METHODS: For transgastric peritoneoscopy,
      carbon dioxide was insufflated via the endoscope for a constant intraperitoneal
      pressure of 6 mmHg or 12 mmHg in 9 pigs each. The quality of transgastric
      peritoneoscopy was rated on a visual analog scale (0 mm, min.; 100 mm, max.) by
      the endoscopist, who was blinded to the intraperitoneal pressure. The cardiac
      index and global end-diastolic volume index (GEDVI, reflecting preload) were
      measured every 3 minutes by transpulmonary thermodilution. The following were
      also recorded: heart rate, mean arterial pressure (MAP), systemic vascular
      resistance index (SVRI, reflecting afterload), peak inspiratory pressure (PIP),
      pH, PCO (2), and PO (2). RESULTS: The quality of transgastric peritoneoscopy with
      the use of low-pressure pneumoperitoneum was not inferior to that obtained using
      standard-pressure pneumoperitoneum (87.0 mm vs. 87.3 mm; P<0.05). In both groups
      we observed a statistically significant rise in MAP and SVRI. The increase in
      SVRI was less pronounced during low-pressure peritoneum ( P=0.042), indicating a
      reduced stress response in comparison to standard-pressure peritoneum. There were
      no relevant differences between the groups in relation to cardiac index, GEDVI,
      and heart rate. An intra-abdominal pressure of 6 mmHg also led to better
      oxygenation ( P=0.031 for difference in PO (2) between the two groups) due to
      lower peak inspiratory pressure ( P<0.001 for difference). There were only slight
      differences between the groups with regard to pH and PCO (2). CONCLUSIONS:
      Pneumoperitoneum of 12-16 mmHg is used for standard laparoscopy. For NOTES, low
      pressure pneumoperitoneum is sufficient and is associated with an improved
      cardiopulmonary response compared to standard-pressure pneumoperitoneum.

PMID- 21732272
TI  - Body mass index increase, serum leptin, adiponectin, neuropeptide Y and lipid
      levels during treatment with olanzapine and haloperidol.
AB  - INTRODUCTION: Body mass index (BMI) increase is an undesired effect associated
      with antipsychotics, and crucial for patients' global health and treatment
      compliance. We aimed to investigate the relation between BMI during olanzapine or
      haloperidol treatments and leptin, neuropeptide Y (NPY), adiponectin and lipid
      serum levels. METHODS: In this 9-month, randomized and naturalist study, 34 male
      patients, 18 on olanzapine and 16 on haloperidol group were enrolled, all were
      under monotherapy. Patient outcome was evaluated with positive and negative
      syndrome scale (PANSS) at every 3-month period. In each visit, BMI, leptin, NPY,
      lipid, olanzapine or haloperidol levels were also monitored. RESULTS AND
      DISCUSSION: Leptin levels positively correlated with BMI in olanzapine (r=0.64,
      p<0.001) and haloperidol (r=0.73, p<0.001) groups; only in olanzapine patients,
      the former also correlated with PANSS score (r=0.54, p<0.05). NPY levels
      negatively correlated with olanzapine levels (r=- 0.65, p<0.01). Adiponectin
      levels had not significantly varied. CONCLUSION: Antipsychotics probably
      interfere on leptin and NPY signalling ways and disturb these hormones in eating
      behaviour control.

PMID- 21732273
TI  - The interplay between macrophages and angiogenesis in development, tissue injury
      and regeneration.
AB  - During organ development and remodeling, macrophages support angiogenesis, not
      only by secreting proangiogenic growth factors and matrix-remodeling proteases,
      but also by physically interacting with the sprouting vasculature to assist the
      formation of complex vascular networks. Recent data further indicate that
      embryonic and tumor-associated macrophages express similar genetic programs,
      possibly suggesting convergent functions in organogenesis and tumorigenesis. In
      this article, we review the role of macrophages in development, tissue injury and
      regeneration, by focusing on the mechanisms used by subsets of these cells, such
      as the TIE2-expressing macrophages, to regulate angiogenesis and
      lymphangiogenesis in both fetal and post-natal life.

PMID- 21732274
TI  - Cancer stem cells and angiogenesis.
AB  - Cancer stem cells (CSCs) or tumor initiating cells were identified and
      characterized as a unique subpopulation with stem cell features in many types of
      cancer. Current CSC studies provide novel insights regarding tumor initiation,
      progression, angiogenesis, resistance to therapy and interplay with the tumor
      micro-environment. A cancer stem cell niche has been proposed based on these
      findings. The niche provides the soil for CSC self-renewal and maintenance,
      stimulating essential signaling pathways in CSCs and leading to secretion of
      factors that promote angiogenesis and long term growth of CSCs. We present
      evidence which has emerged over the past 5 years indicating interaction of CSCs
      with angiogenesis in the proposed "vascular niche". Based on these findings,
      targeting the "cancer stem cell niche" by combining an individualized anti-CSC
      approach with treatment of their microenvironment may represent a novel
      therapeutic strategy against solid tumor systems.

PMID- 21732276
TI  - Evolution of angiogenesis.
AB  - Endothelial cells, which are the main agents of the angiogenic process in
      vertebrates, are lacking in the vessels of invertebrates. These are limited by
      the basement membranes of epithelial or myoepithelial cells. This fact leads to
      the questions of how vessels grow in invertebrates and how vertebrate
      angiogenesis evolved. We herein review the knowledge available about vascular
      growth in invertebrates. The cases described include the ascidian Botryllus, the
      annelid Hirudo and the squid Idiosepius. All these processes of vascular growth
      in invertebrates show substantial differences with the vertebrate angiogenesis,
      although the signalling system mediated by VEGF and its receptor VEGFR seems to
      be involved in all cases. However, VEGF signalling is used by many processes of
      cell directional migration, and it cannot be considered as a hallmark of
      angiogenesis. We also describe the close similarity between the molecular control
      of the endothelial angiogenesis and the branching morphogenesis of the tracheal
      system of insects. In both cases, the process is regulated by hypoxia and
      activates a leading tip cell which inhibits responsiveness of the adjacent cells
      through a Delta/Notch signalling pathway. We suggest that endothelial
      angiogenesis in vertebrates arose through cooption of this hypoxia-sensing
      mechanism by replacing the FGF/FGFR axis of insects by a VEGF/VEGFR-mediated
      system, and adding a second layer of control of the endothelial state (quiescent
      or activated) mediated by angiopoietins and Tie receptors. This evolutionarily
      new control mechanism of endothelial angiogenesis establishes an
      endothelial/perivascular cell crosstalking which does not exist in invertebrates.

PMID- 21732275
TI  - Signal transduction in vasculogenesis and developmental angiogenesis.
AB  - The vasculature is a highly specialized organ that functions in a number of key
      physiological tasks including the transport of oxygen and nutrients to tissues.
      Formation of the vascular system is an essential and rate-limiting step in
      development and occurs primarily through two main mechanisms, vasculogenesis and
      angiogenesis. Both vasculogenesis, the de novo formation of vessels, and
      angiogenesis, the growth of new vessels from pre-existing vessels by sprouting,
      are complex processes that are mediated by the precise coordination of multiple
      cell types to form and remodel the vascular system. A host of signaling molecules
      and their interaction with specific receptors are central to activating and
      modulating vessel formation. This review article summarizes the current state of
      research involving signaling molecules that have been demonstrated to function in
      the regulation of vasculogenesis and angiogenesis, as well as molecules known to
      play a role in vessel maturation, hypoxia-driven angiogenesis and arterial-venous
      specification.

PMID- 21732277
TI  - Angiogenesis in development and cancer today.

PMID- 21732278
TI  - Local inhibition of angiogenesis results in an atrophic non-union in a rat
      osteotomy model.
AB  - Long bone and in particular tibia fractures frequently fail to heal. A disturbed
      revascularisation is supposed to be a major cause for impaired bone healing or
      the development of non-unions. We aim to establish an animal model, which
      reliably mimics the clinical situation. Human microvascular endothelial cells
      (HMEC-1) and primary human osteoblast like cells (POBs) were cultured with
      different angiogenesis-inhibitors (Fumagillin, SU5416, Artesunate and 3,5,4'
      Trimethoxystilbene) released out of poly(D,L-Lactide) (PDLLA) coated k-wires and
      cell activity was determined. Discs containing PDLLA or PDLLA +
      Fumagillin/Artesunate were placed at the chorionallantoic membrane of hen eggs
      and the effect on vessel formation and egg vitality was observed. Tibia osteotomy
      was performed in rats and stabilised with K-wires coated with PDLLA + Fumagillin
      or with PDLLA only (control group). The healing was compared at different time
      points to the PDLLA control. Fumagillin and Artesunate inhibited the activity of
      HMEC-1 with minor effect on POBs. Artesunate caused embryonic death, whereas
      Fumagillin had no effects on egg vitality, but reduced the blood vessels. In the
      animal study all rats showed an impaired healing with reduced biomechanical
      stability. The Fumagillin treated tibiae had a significantly decreased callus
      size at day 42 and 84, less blood vessels in the early callus, a reduced
      histological callus size at day 10, 28 and 84, as well as an altered callus
      composition. This study presents a less vascularised, atrophic, tibia non-union
      and can be used in further investigations to analyse the pathology of atrophic
      non-union and to test new interventions.

PMID- 21732279
TI  - Osteogenic differentiation of bone marrow-derived mesenchymal stromal cells on
      bone-derived scaffolds: effect of microvibration and role of ERK1/2 activation.
AB  - Although in vivo studies have shown that low-magnitude, high-frequency (LMHF)
      vibration (LM: < 1 *g; HF: 20-90 Hz) exhibits anabolic effects on skeletal
      homeostasis, the underlying cellular/molecular regulation involved in bone
      adaptation to LMHF vibration is little known. In this report, we tested the
      effects of microvibration (magnitude: 0.3 *g, frequency: 40 Hz, amplitude: +/- 50
      MUm, 30 min/12 h) on proliferation and osteodifferentiation of bone marrow
      derived mesenchymal stromal cells (BMSCs) seeded on human bone-derived scaffolds.
      The scaffolds were prepared by partial demineralisation and deproteinisation.
      BMSCs were allowed to attach to the scaffolds for 3 days. Morphological study
      showed that spindle-shaped BMSCs almost completely covered the surface of bone
      derived scaffold and these cells expressed higher ALP activity than those
      cultured on plates. After microvibration treatment, BMSC proliferation was
      decreased on day 7 and 10; however, numbers of genes and proteins expressed
      during osteogenesis, including Cbfa1, ALP, collagen I and osteocalcin were
      greatly increased. ERK1/2 activation was involved in microvibration-induced BMSC
      osteogenesis. Taken together, this study suggests that bone-derived scaffolds
      have good biocompatibility and show osteoinductive properties. By increasing the
      osteogenic lineage commitment of BMSCs and enhancing osteogenic gene expressions,
      microvibration promotes BMSC differentiation and increase bone formation of BMSCs
      seeded on bone-derived scaffolds. Moreover, ERK1/2 pathway plays an important
      role in microvibration-induced osteogenesis in BMSC cellular scaffolds.

PMID- 21732280
TI  - CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory
      capacity of mesenchymal stromal cells.
AB  - e assumption that mesenchymal stromal cell (MSC)-based-therapies are capable of
      augmenting physiological regeneration processes has fostered intensive basic and
      clinical research activities. However, to achieve sustained therapeutic success
      in vivo, not only the biological, but also the mechanical microenvironment of
      MSCs during these regeneration processes needs to be taken into account. This is
      especially important for e.g., bone fracture repair, since MSCs present at the
      fracture site undergo significant biomechanical stimulation. This study has
      therefore investigated cellular characteristics and the functional behaviour of
      MSCs in response to mechanical loading. Our results demonstrated a reduced
      expression of MSC surface markers CD73 (ecto-5'-nucleotidase) and CD29 (integrin
      beta1) after loading. On the functional level, loading led to a reduced migration
      of MSCs. Both effects persisted for a week after the removal of the loading
      stimulus. Specific inhibition of CD73/CD29 demonstrated their substrate dependent
      involvement in MSC migration after loading. These results were supported by
      scanning electron microscopy images and phalloidin staining of actin filaments
      displaying less cell spreading, lamellipodia formation and actin accumulations.
      Moreover, focal adhesion kinase and Src-family kinases were identified as
      candidate downstream targets of CD73/CD29 that might contribute to the
      mechanically induced decrease in MSC migration. These results suggest that MSC
      migration is controlled by CD73/CD29, which in turn are regulated by mechanical
      stimulation of cells. We therefore speculate that MSCs migrate into the fracture
      site, become mechanically entrapped, and thereby accumulate to fulfil their
      regenerative functions.

PMID- 21732281
TI  - Correspondence between performance of Eucalyptus spp trees selected from family
      and clonal tests.
AB  - We examined the correspondence in performance between trees selected from a
      family test and their respective clones from a clonal test of Eucalyptus. Full
      sib families were obtained from controlled pollination among individuals of
      Eucalyptus grandis and between E. grandis and E. urophylla. The hybridizations
      did not follow a factorial scheme. The family tests were carried out at three
      locations in Eunapolis and Itabela counties, in Bahia, Brazil, in 2003. Four
      hundred and ninety-seven high-performance trees were selected, by the individual
      BLUP procedure, in the family tests at two years of age, based on wood volume.
      The clones from these trees and 14 checks were evaluated in clonal tests carried
      out in the same region in 2006. The wood volume of the clones was evaluated at
      two years of age. Trait correlation between the trees selected from the family
      and clonal tests was low. The estimate of the coincidence between the best trees
      and the best clones using an average of the different intensities of selection
      was only 27%. These results demonstrate that the selection of trees in the family
      test should not be too drastic; otherwise the chance plus clones may be
      overlooked.

PMID- 21732282
TI  - Genetic differentiation in Aspidosperma polyneuron (Apocynaceae) over a short
      geographic distance as assessed by AFLP markers.
AB  - Studies on intraspecific variation can contribute to the development of
      conservation strategies by identifying units of conservation for threatened
      species. Aspidosperma polyneuron is a tropical tree of seasonal semideciduous
      forests that is currently endangered and protected because it has been heavily
      logged for lumber, although it was once common in Brazil and neighboring
      countries. We investigated genetic structure in two samples of A. polyneuron
      collected from steep hillsides and from flat areas of a natural forest fragment
      in northern Parana State, Brazil. Seven AFLP primer combinations yielded 200
      markers, with a polymorphic rate of 88.5% for samples from the flat area and 99%
      for samples from the high declivity area. Total genetic diversity (H(T)) was
      0.387, while the genetic diversity within the populations (H(S)) was 0.307 and
      0.372, for samples from the flat and the high declivity areas, respectively.
      Genetic differentiation between samples was high, with a mean F(ST) of 0.265 and
      a genetic distance of 0.148, indicative of a high degree of genetic structure
      over a short distance. Principal coordinate analysis separated the samples into
      three groups of individuals; the first group included individuals from the high
      declivity area, the second group consisted of individuals only from the flat
      area, and the third group had individuals from both areas. Bayesian analysis also
      showed K = 3 clusters. The unexpected high level of intraspecific variation of A.
      polyneuron in this small forest fragment should be taken into account when
      evaluating the genetic impact of forest degradation on this species in other
      semideciduous forest fragments.

PMID- 21732283
TI  - Identification and isolation of full-length cDNA sequences by sequencing and
      analysis of expressed sequence tags from guarana (Paullinia cupana).
AB  - The current intense production of biological data, generated by sequencing
      techniques, has created an ever-growing volume of unanalyzed data. We reevaluated
      data produced by the guarana (Paullinia cupana) transcriptome sequencing project
      to identify cDNA clones with complete coding sequences (full-length clones) and
      complete sequences of genes of biotechnological interest, contributing to the
      knowledge of biological characteristics of this organism. We analyzed 15,490 ESTs
      of guarana in search of clones with complete coding regions. A total of 12,402
      sequences were analyzed using BLAST, and 4697 full-length clones were identified,
      responsible for the production of 2297 different proteins. Eighty-four clones
      were identified as full-length for N-methyltransferase and 18 were sequenced in
      both directions to obtain the complete genome sequence, and confirm the search
      made in silico for full-length clones. Phylogenetic analyses were made with the
      complete genome sequences of three clones, which showed only 0.017%
      dissimilarity; these are phylogenetically close to the caffeine synthase of
      Theobroma cacao. The search for full-length clones allowed the identification of
      numerous clones that had the complete coding region, demonstrating this to be an
      efficient and useful tool in the process of biological data mining. The
      sequencing of the complete coding region of identified full-length clones
      corroborated the data from the in silico search, strengthening its efficiency and
      utility.

PMID- 21732284
TI  - Risk of colorectal cancer associated with the methylenetetrahydrofolate reductase
      (MTHFR) C677T polymorphism in the Kashmiri population.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate
      metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The
      two common functional polymorphisms of MTHFR, 677 C->T and 1298 A->C, have been
      shown to impact various diseases, including cancer. The 677 C->T polymorphism has
      been widely investigated in different cancers and has been implicated as a risk
      factor for the development of various cancers. We investigated MTHFR C677T
      genotype frequency in colorectal cancer cases in the Kashmiri population and
      correlated this information with the known clinicopathological characters of
      colorectal cancer, in a case-control study. Eighty-six colorectal cancer cases
      were studied for MTHFR C677T polymorphism, compared to 160 controls taken from
      the general population, employing the PCR-RFLP technique. We found the frequency
      of the three different genotypes of MTHFR in our ethnic Kashmir population, i.e.,
      CC, CT and TT, to be 68.6, 20.9 and 10.4% among colorectal cancer cases and 75.6,
      16.9 and 7.5% among the general control population, respectively. There was a
      significant association between the MTHFR TT genotype and colorectal cancer in
      the higher age group. We conclude that the MTHFR C677T polymorphism slightly
      increases the risk for colorectal cancer development in our ethnic Kashmir
      population.

PMID- 21732285
TI  - Genetic diversity in wild sweet cherries (Prunus avium) in Turkey revealed by SSR
      markers.
AB  - Wild sweet cherry (Prunus avium) trees are abundant in the northern part of
      Turkey, including the Coruh Valley. We analyzed 18 wild sweet cherry genotypes
      collected from diverse environments in the upper Coruh Valley in Turkey to
      determine genetic variation, using 10 SSR primers. These SSR primers generated 46
      alleles; the number of alleles per primer ranged from 3 to 7, with a mean of 4.6.
      The primer PS12A02 gave the highest number of polymorphic bands (N = 7), while
      CPSCT010, UDAp-401 and UDAp-404 gave the lowest number (N = 3). Seven groups were
      separated in the dendrogram, although most of the genotypes did not cluster
      according to phenological and morphological traits. This level of genetic
      diversity in these wild sweet cherry genotypes is very high and therefore these
      trees would be useful as breeders for crosses between cultivated sweet cherry and
      wild genotypes.

PMID- 21732286
TI  - Candidate gene region for control of rib eye area in Canchim beef cattle.
AB  - Investigation of molecular marker effects on production traits is essential to
      define marker assisted selection strategies in beef cattle. We looked for a
      possible association of molecular markers and backfat thickness (BFT) and rib eye
      area (REA) in Canchim (5/8 Charolais + 3/8 Zebu) and MA (offspring of Charolais
      bulls and 1/2 Canchim + 1/2 Zebu cows) animals raised exclusively on pasture.
      Traits were measured on 987 individuals from seven herds from two Brazilian
      States (Sao Paulo and Goias), in March and April from 2005 to 2007, when animals
      were, on average, 19 months of age. Five microsatellite markers lying in QTL
      regions for BFT and REA (BMS490 and ETH10 on chromosome 5, INRA133 and ILSTS090
      on chromosome 6, and BMS2142 on chromosome 19) were genotyped and association
      analyses were performed under an animal model using the restricted maximum
      likelihood method. After correction for multiple tests, a significant effect of
      microsatellite BMS490 on REA was observed, suggesting that at least one QTL
      affecting carcass traits in this region of the BTA5. No significant effect on BFT
      was observed for these markers.

PMID- 21732287
TI  - Breeding value accuracy estimates for growth traits using random regression and
      multi-trait models in Nelore cattle.
AB  - We quantified the potential increase in accuracy of expected breeding value for
      weights of Nelore cattle, from birth to mature age, using multi-trait and random
      regression models on Legendre polynomials and B-spline functions. A total of
      87,712 weight records from 8144 females were used, recorded every three months
      from birth to mature age from the Nelore Brazil Program. For random regression
      analyses, all female weight records from birth to eight years of age (data set I)
      were considered. From this general data set, a subset was created (data set II),
      which included only nine weight records: at birth, weaning, 365 and 550 days of
      age, and 2, 3, 4, 5, and 6 years of age. Data set II was analyzed using random
      regression and multi-trait models. The model of analysis included the
      contemporary group as fixed effects and age of dam as a linear and quadratic
      covariable. In the random regression analyses, average growth trends were modeled
      using a cubic regression on orthogonal polynomials of age. Residual variances
      were modeled by a step function with five classes. Legendre polynomials of fourth
      and sixth order were utilized to model the direct genetic and animal permanent
      environmental effects, respectively, while third-order Legendre polynomials were
      considered for maternal genetic and maternal permanent environmental effects.
      Quadratic polynomials were applied to model all random effects in random
      regression models on B-spline functions. Direct genetic and animal permanent
      environmental effects were modeled using three segments or five coefficients, and
      genetic maternal and maternal permanent environmental effects were modeled with
      one segment or three coefficients in the random regression models on B-spline
      functions. For both data sets (I and II), animals ranked differently according to
      expected breeding value obtained by random regression or multi-trait models. With
      random regression models, the highest gains in accuracy were obtained at ages
      with a low number of weight records. The results indicate that random regression
      models provide more accurate expected breeding values than the traditionally
      finite multi-trait models. Thus, higher genetic responses are expected for beef
      cattle growth traits by replacing a multi-trait model with random regression
      models for genetic evaluation. B-spline functions could be applied as an
      alternative to Legendre polynomials to model covariance functions for weights
      from birth to mature age.

PMID- 21732288
TI  - Phylogenetic study and barcoding of the blood cockle, Tegillarca granosa, found
      on the west coast of peninsular Malaysia using the COI gene.
AB  - Blood cockles are among the most economically important brackish water
      invertebrates found in Malaysia. However, our knowledge of blood cockle phylogeny
      and systematics is rudimentary, especially for the species Tegillarca granosa. It
      is unclear, for instance, whether the cockles occurring on the west coast of
      peninsular Malaysia constitute a single species, or multiple, phylogenetically
      distinct species. We performed the first DNA molecular phylogenetic analysis of
      T. granosa to distinguish it from other related species found in other parts of
      the world and to create a DNA database for the species. An approximately 585
      nucleotide fragment of the mitochondrial DNA (cytochrome oxidase I, COI) was
      sequenced for 150 individual cockles, representing 10 populations: three from the
      north, four from the central part and three from the southern part of peninsular
      Malaysia. Phylogenetic analyses of the resulting dataset yielded tree topologies
      that not only showed the relationship between T. granosa and its closest
      relatives but its position in the evolutionary tree. Three mitochondrial clades
      were evident, each containing an individual genus. Using the mutation rate of the
      COI gene, the divergence time between T. granosa and its closest related species
      was estimated to be 460 thousand years ago. This study provides a phylogenetic
      framework for this ecologically prominent and commercially important cockle
      species.

PMID- 21732289
TI  - Utilization of molecular markers for the conservation of blood cockles, Anadara
      granosa (Arcidae).
AB  - We examined genetic variation in blood cockles in an effort to obtain information
      useful for the sustainability, management, and the stability of this species as a
      major commodity in the fisheries sector. Ten populations of cockles were sampled
      from the north to the south of the west coast of peninsular Malaysia. The cockles
      were collected in collaboration with the Fisheries Research Institute, Penang.
      The population genetic analysis of the cockles were studied via RAPD-PCR and
      mtDNA sequencing. Three hundred individuals were analyzed with RAPD-PCR
      experiments. High gene diversity over all loci was observed (Shannon index =
      0.549 +/- 0.056 and Nei's gene diversity = 0.4852 +/- 0.0430 among 35 loci). The
      second method, mtDNA sequencing, was employed to complement the information
      obtained from RAPD-PCR. The gene selected for mtDNA sequencing was cytochrome c
      oxidase I (COI). One hundred and fifty individuals were sequenced, yielding a
      partial gene of 585 bp. Statistical analysis showed homogeneity in general but
      did reveal some degree of variability between the populations in Johor and the
      rest of the populations. The Mantel test showed a positive but nonsignificant
      correlation between geographic and genetic distances (r = 0.2710, P = 0.622), as
      in the RAPD analysis. We propose that the homogeneity between distant populations
      is caused by two factors: 1) the translocation of the spats; 2) larvae are
      carried by current movement from the north of the peninsula to the south. The
      different genetic composition found in Johor could be due to pollution, mutagenic
      substances or physical factors such as the depth of the water column. This
      population genetic study is the first for this species in peninsular Malaysia.
      The data from this study have important implications for fishery management,
      conservation of blood cockles and translocation policies for aquaculture and
      stock enhancement programs.

PMID- 21732290
TI  - Expressed sequence tag-simple sequence repeat-based molecular variance in two
      Salicornia (Amaranthaceae) populations.
AB  - Salicornia spp is one of the most salt-tolerant vascular plants and is native to
      salt marshes and estuaries. We developed expressed sequence tag derived-simple
      sequence repeat (EST-SSR) markers for estimating genetic diversity and marker
      assisted Salicornia breeding. Six polymorphic EST-SSRs of 40 detected 27 alleles,
      ranging from three to five alleles per locus. The average number of alleles per
      locus was 4.33 and 4.17, and the major allele frequency at locus DY529765 was
      high, being 0.859 and 0.857 in S. bigelovii and S. europea, respectively. Gene
      diversity, heterozygosity and polymorphism information content were highest at
      locus DY529950 and similar in these two species. Gene diversity increased with
      increase in the number of alleles that had a low major allele frequency at a
      locus. Six polymorphic loci effectively discriminated 46 taxa into three clusters
      via different analyses. Significant deviation of F(ST) from zero in three
      suggested populations for six loci indicated population differentiation and
      limited gene flow among them. A reduced median network established that taxon
      SB65 is primitive. SMART (simple modular architecture research tool) analysis of
      peptide sequences of six EST-SSRs showed that loci DY529765, DY529950 and
      EC906203 contained transmembrane, TLC, AgrB and NTR domains and might be involved
      in salinity stress tolerance. These EST-SSRs are a valuable resource for marker
      development and may be useful in marker-assisted Salicornia breeding.

PMID- 21732291
TI  - In silico characterization of putative members of the coffee (Coffea arabica)
      ethylene signaling pathway.
AB  - The plant hormone ethylene is involved in several developmental and physiological
      processes in plants, including senescence, fruit ripening and organ abscission,
      as well as in biotic and abiotic stress responses. Initiation of these processes
      involves complex regulation of both ethylene biosynthesis and the ability of
      cells to perceive the hormone and respond in an appropriate manner, a process
      which is regulated both spatially and temporally. Ethylene is a gaseous hormone
      whose sensitivity is a key factor to limiting its response in target cells. We
      made a search of the Coffee Expressed Sequence Tag (CAFEST) database for
      expressed sequence tags related to known elements of the ethylene signaling
      pathway. Sequences showing a reliable similarity were clusterized, annotated and
      analyzed for conserved domains. Multiple alignments comprising the sequences that
      we found and sequences of ethylene signaling elements from other species were
      made, and their phylogeny was assessed by phylogenetic trees constructed with the
      MEGA4 software. The expression profile was assessed by in silico Northern blot
      analysis performed using the Cluster and TreeView programs. The CAFEST database
      was found to have a large number of sequences related to previously described
      ethylene signaling pathway elements, allowing identification of putative members
      from almost every step of this pathway. The phylogenetic trees demonstrated high
      similarity between the sequences found in the CAFEST and those from other
      species, and the electronic Northern blot analysis detected their expression in
      various tissues, development stages and stress conditions.

PMID- 21732292
TI  - Plasticity of Corynebacterium diphtheriae pathogenicity islands revealed by PCR.
AB  - Despite the existence of a vaccine against diphtheria, this disease remains
      endemic and is reemerging in several regions due to many factors, including
      variations in genes coding for virulence factors. One common feature of virulence
      factors is their high concentration in pathogenicity islands (PAIs), very
      unstable regions acquired via horizontal gene transfer, which has lead to the
      emergence of various bacterial pathogens. The 13 putative PAIs in Corynebacterium
      diphtheriae NCTC 13129 and the reemergence of this disease point to the great
      variability in the PAIs of this species, which may reflect on bacterial life
      style and physiological versatility. We investigated the relationships between
      the large number of PAIs in C. diphtheriae and the possible implications of their
      plasticity in virulence. The GenoFrag software was used to design primers to
      analyze the genome plasticity of two pathogenicity islands of the reference
      strain (PiCds 3 and 8) in 11 different strains. We found that PiCd 3 was absent
      in only two strains, showing genes playing putative important roles in virulence
      and that only one strain harbored PiCd 8, due to its location in a putative
      "hotspot" for horizontal gene transfer events.

PMID- 21732293
TI  - [Osteoporosis].

PMID- 21732295
TI  - ["On the etiology of stroke and prevention". PRAXIS 28 January 1932].

PMID- 21732296
TI  - [Spinal tumors - part 1: extradural tumors. Epidemiology, clinical aspects and
      therapy].
AB  - Spinal tumors are classified according to their location in extradural,
      intradural-extramedullary, and intradural-intramedullary tumors. The most
      frequent extradural tumors are metastases. Primary spinal tumors are rare and
      predominantly benign. Independent of their origin, spinal tumors manifest
      themselves with progressive local or radicular pain and neurological deficits. A
      preferably early diagnosis and subsequent therapy is important to improve the
      prognosis. The treatment of choice for most of these tumors is the complete
      surgical resection. In particular with the occurrence of neurological deficits a
      fast surgical intervention is indicated, since the prognosis depends on duration
      and severity of the preoperative existing deficits. Below, clinical presentation
      and relevant treatment options of spinal extradural tumors are discussed.

PMID- 21732297
TI  - [Spinal tumors - part 2: intradural tumors. Epidemiology, clinical aspects and
      therapy].
AB  - Intradural spinal tumors are classified in extra- and intramedullary tumors. The
      most frequent intradural-extramedullary tumors are meningiomas and neurinomas.
      Among the intradural-intramedullary tumors the most frequent ones are ependymomas
      and astrocytomas. Independent of their origin, spinal tumors usually manifest
      with progressive local or radicular pain and neurological deficits. The treatment
      of choice for most of these tumors is a complete surgical resection. In tumors
      with infiltrative growth into the intramedullary area, a marginal tumor tissue
      has to be left in situ in order to avoid additional neurological deficits. In
      particular if neurological deficits appear, a fast surgical intervention is
      indicated, since the prognosis depends on duration and severity of the
      preoperative existing deficits. Below, clinical presentation and relevant
      treatment options of spinal intradural tumors are discussed.

PMID- 21732298
TI  - [Comment from tHE cardiologic-angiologic viewpoint].

PMID- 21732299
TI  - [Statins in primary prevention - a must for the general practitioner?].

PMID- 21732300
TI  - [Extrauterine pregnancy].

PMID- 21732301
TI  - [No complaints, but constantly elevated cholestatic serum liver tests].
AB  - A 75 year old woman presented with long-lasting pruritus and elevation of serum
      levels of alkaline phosphatase and gamma-glutamyl transpeptidase (GGT).
      Potentially hepatotoxic drugs were stopped; an abdominal ultra-sonography was
      normal. Antimitochondrial antibodies were elevated and are the serologic hallmark
      of primary biliary cirrhosis. The disease can progress from an asymptomatic
      inflammation to a cirrhosis. The disease-modifying treatment consists in
      ursodeoxycholic acid 13-15 mg/kg per day. Concomitant to the primary biliary
      cirrhosis hypothyroidism, osteoporosis, malabsorption and dyslipidemia can occur.

PMID- 21732302
TI  - [Not Available].

PMID- 21732303
TI  - [Not Available].

PMID- 21732308
TI  - Setting up and running an advanced light microscopy and imaging facility.
AB  - During the last twenty years, interest in light microscopy and imaging techniques
      has grown in various fields, such as molecular and cellular biology,
      developmental biology, and neurobiology. In addition, the number of scientific
      articles and journals using these techniques is rapidly increasing. Nowadays,
      most research institutions require sophisticated microscopy systems to cover
      their investigation demands. In general, such instruments are too expensive and
      complex to be purchased and managed by a single laboratory or research group, so
      they have to be shared with other groups and supervised by specialized personnel.
      This is the reason why microscopy and imaging facilities are becoming so
      important at research institutions nowadays. In this unit, we have gathered and
      presented a number of issues and considerations from our own experience that we
      hope will be helpful when planning or setting up a new facility.

PMID- 21732309
TI  - Photoactivation and imaging of optical highlighter fluorescent proteins.
AB  - A major advance in the microscopic study of cells and tissues is the introduction
      of photoactivatable fluorescent proteins, which can specifically mark proteins of
      interest within a living cell. Fluorescent proteins are now available that allow
      a pool of molecules to be "turned on" by photoactivation. This unit discusses
      technical aspects for the general use of photoactivatable fluorescent proteins
      and introduces some specific applications in the concluding remarks.

PMID- 21732310
TI  - Zinc fixation for flow cytometry analysis of intracellular and surface epitopes,
      DNA content, and cell proliferation.
AB  - Zinc salt-based fixation (ZBF) is a simple, cost-effective, and nonhazardous
      fixation method for cell suspensions that preserves all cellular structures and
      enables flow cytometric analysis of both surface and intracellular proteins, DNA
      content profiles, and pulse-labeling using the thymidine analog EdU in the same
      cell sample. ZBF performs equally well to formaldehyde in the preservation of
      surface epitope labeling and forward and side light scatter parameters, as
      measured by flow cytometry. DNA is maintained at high molecular weight, improving
      the quantification and allowing subsequent quantitative PCR analysis. Finally,
      ZBF treatment allows for long-term storage of labeled cells with little change in
      these parameters.

PMID- 21732311
TI  - Quantitation of DNA and RNA with absorption and fluorescence spectroscopy.
AB  - Quantitation of nucleic acids is a fundamental tool in molecular biology that
      requires accuracy, reliability, and the use of increasingly smaller sample
      volumes. This unit describes the traditional absorbance measurement at 260 nm and
      three more sensitive fluorescence techniques employing Hoechst 33258, ethidium
      bromide, and PicoGreen. The range of the assays covers 25 pg/ml to 50 ug/ml.
      Absorbance at 260 nm has an effective range from 1 to 50 ug/ml; Hoechst 33258
      from 0.01 to 15 ug/ml; ethidium bromide from 0.1 to 10 ug/ml; and PicoGreen from
      25 to 1000 pg/ml.

PMID- 21732312
TI  - Basic confocal microscopy.
AB  - This unit introduces the reader to the basic principles of confocal microscopy
      and the design and capabilities of current confocal microscopes. The advantages
      and disadvantages of confocal microscopy compared to other techniques for
      fluorescence imaging are described. There are also practical guidelines for
      sample preparation and optimization of imaging parameters, as well as examples of
      some of the applications of confocal microscopy.

PMID- 21732313
TI  - In vitro analysis of mouse mesencephalic neural crest development.
AB  - The neural crest is a unique structure in vertebrates. Neural crest cells play
      important roles in the formation of organs that characterize the vertebrate body
      plan. In this unit, we describe a primary culture method for mouse mesencephalic
      neural crest cells. The neural crest cells cultured by this method actively
      proliferate and differentiate into various cell types that originate from cranial
      neural crest cells, such as chondrocytes, neurons, and glia. Therefore, this
      primary culture method is useful for analyzing the development of mouse
      mesencephalic neural crest cells.

PMID- 21732314
TI  - Automated three-chambered social approach task for mice.
AB  - Autism is diagnosed by three major symptom categories: unusual reciprocal social
      interactions, impaired communication, and repetitive behaviors with restricted
      interests. Direct social approach in mice has strong face validity to simple
      social approach behaviors in humans, which are frequently impaired in autism.
      This unit presents a basic protocol for a standardized, high-throughput social
      approach test for assaying mouse sociability. Our automated three-chambered
      social approach task quantifies direct social approach behaviors when a subject
      mouse is presented with the choice of spending time with either a novel mouse or
      a novel object. Sociability is defined as the subject mouse spending more time in
      the chamber containing the novel target mouse than in the chamber containing the
      inanimate novel object. The Basic Protocol describes procedures for testing one
      subject at a time in a single apparatus. A Support Protocol addresses data
      collection.

PMID- 21732315
TI  - Stem-loop RT-qPCR for miRNAs.
AB  - This unit presents a specific and sensitive quantitative reverse-transcription
      PCR (RT-qPCR) method for measuring individual microRNAs (miRNAs) in tissue or
      cultured cells. miRNAs are 17 to 24 nucleotides (nt) in length. Standard and
      quantitative PCR methods require a template that is at least two times the length
      of either of the specific forward or reverse primers, each typically ~ 20 nt in
      length. Thus, the target minimum length is >= 40 nt, making miRNAs too short for
      standard RT-qPCR methods. In this assay, each of the RT-qPCR nucleic acid
      reagents, including the RT-primer, the forward and reverse PCR primers, and the
      hydrolysis probe, contain design features that, together, optimize miRNA
      specificity and assay sensitivity. The RT-primer contains a highly stable stem
      loop structure that lengthens the target cDNA. The forward PCR primer adds
      additional length with nucleotides that optimize its melting temperature (T(m))
      and enhance assay specificity. The reverse primer disrupts the stem loop. Assay
      specificity is further optimized by placement of the probe over much of the
      original miRNA sequence, and the probe T(m) is optimized by addition of a minor
      groove binding (MGB) moiety.

PMID- 21732316
TI  - Detection and analysis of proteins modified by O-linked N-acetylglucosamine.
AB  - O-GlcNAc is a common post-translational modification of nuclear, mitochondrial,
      and cytoplasmic proteins that is implicated in the etiology of type II diabetes
      and Alzheimer's disease, as well as cardioprotection. This unit covers simple and
      comprehensive techniques for identifying proteins modified by O-GlcNAc, studying
      the enzymes that add and remove O-GlcNAc, and mapping O-GlcNAc modification
      sites.

PMID- 21732318
TI  - Recombineering-based procedure for creating BAC transgene constructs for animals
      and cell lines.
AB  - The use of BAC/P1 as a vector for the generation of a transgene has gained
      popularity after the genomic annotation of many organisms was completed (often
      based on the respective BAC library). Large-scale generation of BAC transgenic
      mice has proven that BAC transgene approaches have less integration position
      effects and dosage artifacts when compared with traditional transgenic
      approaches. Also, a BAC can achieve the same tissue-specific expression as a
      knock-in of the same gene with less effort and shorter time of establishment. The
      lambda-RED recombinogenic system has been used to manipulate DNA constructs with
      site-directed mutagenesis, truncation, and tagging with an epitope tag or as a
      fusion protein by homologous recombination, as well as used here to modify many
      BACs with various transgenes. The recombineering plasmid, pKD46, is used to
      fabricate BAC transgenic constructs that can be used in generating transgenic
      organisms as well as used in mammalian cell culture.

PMID- 21732317
TI  - Simultaneous single-molecule mapping of protein-DNA interactions and DNA
      methylation by MAPit.
AB  - Sites of protein binding to DNA are inferred from footprints or spans of
      protection against a probing reagent. In most protocols, sites of accessibility
      to a probe are detected by mapping breaks in DNA strands. As discussed in this
      unit, such methods obscure molecular heterogeneity by averaging cuts at a given
      site over all DNA strands in a sample population. The DNA methyltransferase
      accessibility protocol for individual templates (MAPit), an alternative method
      described in this unit, localizes protein-DNA interactions by probing with
      cytosine-modifying DNA methyltransferases followed by bisulfite sequencing.
      Sequencing individual DNA products after amplification of bisulfite-converted
      sequences permits assignment of the methylation status of every enzyme target
      site along a single DNA strand. Use of the GC-methylating enzyme M.CviPI allows
      simultaneous mapping of chromatin accessibility and endogenous CpG methylation.
      MAPit is therefore the only footprinting method that can detect subpopulations of
      molecules with distinct patterns of protein binding or chromatin architecture and
      correlate them directly with the occurrence of endogenous methylation. Additional
      advantages of MAPit methylation footprinting as well as considerations for
      experimental design and potential sources of error are discussed.

PMID- 21732319
TI  - Isolation by distance between spouses and its effect on children's growth in
      height.
AB  - Heterosis is thought to be an important contributor to human growth and
      development. Marital distance (distance between parental birthplaces) is commonly
      considered as a factor favoring the occurrence of heterosis and can be used as a
      proximate measure of its level. The aim of this study is to assess the net effect
      of expected heterosis resulting from marital migration on the height of
      offspring, controlling for midparental height and socioeconomic status (SES).
      Height measurements on 2,675 boys and 2,603 girls ages 6 to 18 years from
      Ostrowiec Swietokrzyski, Poland were analyzed along with sociodemographic data
      from their parents. Midparental height was calculated as the average of the
      reported heights of the parents. Analyses revealed that marital distance,
      midparental height, and SES had a significant effect on height in boys and girls.
      The net effect of marital distance was much more marked in boys than girls,
      whereas other factors showed comparable effects. Marital distance appears to be
      an independent and important factor influencing the height of offspring.
      According to the "isolation by distance" hypothesis, greater distance between
      parental birthplaces may increase heterozygosity, potentially promoting
      heterosis. We propose that these conditions may result in reduced metabolic costs
      of growth among the heterozygous individuals.

PMID- 21732320
TI  - Modeling neolithic dispersal in central Europe: demographic implications.
AB  - On the basis of new examination of ancient DNA and craniometric analyses,
      Neolithic dispersal in Central Europe has been recently explained as reflecting
      colonization or at least a major influx of near eastern farmers. Given the fact
      that Neolithic dispersal in Central Europe was very rapid and extended into a
      large area, colonization would have to be associated with high population growth
      and fertility rates of an expanding Neolithic population. We built three
      demographic models to test whether the growth and fertility rates of Neolithic
      farmers were high enough to allow them to colonize Central Europe without
      admixture with foragers. The principle of the models is based on stochastic
      population projections. Our results demonstrate that colonization is an unlikely
      explanation for the Neolithic dispersal in Central Europe, as the majority of
      fertility and growth rate estimates obtained in all three models are higher than
      levels expected in the early Neolithic population. On the basis of our models, we
      derived that colonization would be possible only if (1) more than 37% of women
      survived to mean age at childbearing, (2) Neolithic expansion in Central Europe
      lasted more than 150 years, and (3) the population of farmers grew in the entire
      settled area. These settings, however, represent very favorable demographic
      conditions that seem unlikely given current archaeological and demographic
      evidence. Therefore, our results support the view that Neolithic dispersal in
      Central Europe involved admixture of expanding farmers with local foragers. We
      estimate that the admixture contribution from foragers may have been between 55%
      and 72%.

PMID- 21732321
TI  - Technical note: a landmark-based approach to the study of the ear ossicles using
      ultra-high-resolution X-ray computed tomography data.
AB  - Previous study of the ear ossicles in Primates has demonstrated that they vary on
      both functional and phylogenetic bases. Such studies have generally employed two
      dimensional linear measurements rather than three-dimensional data. The
      availability of Ultra- high-resolution X-ray computed tomography (UhrCT) has made
      it possible to accurately image the ossicles so that broadly accepted
      methodologies for acquiring and studying morphometric data can be applied. Using
      UhrCT data also allows for the ossicular chain to be studied in anatomical
      position, so that it is possible to consider the spatial and size relationships
      of all three bones. One issue impeding the morphometric study of the ear ossicles
      is a lack of broadly recognized landmarks. Distinguishing landmarks on the
      ossicles is difficult in part because there are only two areas of articulation in
      the ossicular chain, one of which (the malleus/incus articulation) has a complex
      three-dimensional form. A measurement error study is presented demonstrating that
      a suite of 16 landmarks can be precisely located on reconstructions of the
      ossicles from UhrCT data. Estimates of measurement error showed that most
      landmarks were highly replicable, with an average CV for associated interlandmark
      distances of less than 3%. The positions of these landmarks are chosen to reflect
      not only the overall shape of the bones in the chain and their relative
      positions, but also functional parameters. This study should provide a basis for
      further examination of the smallest bones in the body in three dimensions.

PMID- 21732322
TI  - Interactions of beta-lactoglobulin with serotonin and arachidonyl serotonin.
AB  - beta-Lactoglobulin (beta-LG) is a lipocalin, which is the major whey protein of
      cow's milk and the milk of other mammals. However, it is absent from human milk.
      The biological function of beta-LG is not clear, but its potential role in
      carrying fatty acids through the digestive tract has been suggested. beta-LG has
      been found in complexes with lipids such as butyric and oleic acids and has a
      high affinity for a wide variety of compounds. Serotonin (5-hydroxytryptamine, 5
      HT), an important compound found in animals and plants, has various functions,
      including the regulation of mood, appetite, sleep, muscle contraction, and some
      cognitive functions such as memory and learning. In this study, the interaction
      of serotonin and one of its derivatives, arachidonyl serotonin (AA-5HT), with
      beta-LG was investigated using circular dichroism (CD) and fluorescence intensity
      measurements. These two ligands interact with beta-LG forming equimolar
      complexes. The binding constant for the serotonin/beta-LG interaction is between
      105 and 106 M(-1) , whereas for the AA-5HT/beta-LG complex it is between 104 and
      105 M(-1) as determined by measurements of either protein or ligand fluorescence.
      The observed binding affinities were higher in hydroethanolic media (25% EtOH).
      The interactions between serotonin/beta-LG and AA-5HT/beta-LG may compete with
      self-association (micellization) of both the ligand and the protein. According to
      far- and near-UV CD results, these ligands have no apparent influence on beta-LG
      secondary structure, however they partially destabilize its tertiary structure.
      Their binding by beta-LG may be one of the peripheral mechanisms of the
      regulation of the content of serotonin and its derivatives in the bowel of milk
      fed animals.

PMID- 21732323
TI  - Isothermal titration calorimetry study of the polyelectrolyte complexation of
      xanthan and chitosan samples of different degree of polymerization.
AB  - Mixing oppositely charged polyelectrolytes in aqueous solutions leads to the
      spontaneous formation of polyelectrolyte complexes. Here, we characterize the
      interaction between xanthan of two different chain lengths, a tri-glucosamine and
      a chitosan polymer by isothermal titration calorimetry (ITC). Analysis of the
      experimental thermodynamic data assuming a single set of identical sites
      indicated both enthalpic and entropic contributions to the overall interaction in
      the interaction between xanthan and tri-glucosamine. The relative contribution of
      entropy compared to enthalpy was found to be largest for the shortest chain
      length of xanthan. Using a chitosan polymer instead of tri-glucosamine gave rise
      to two different stages in the interaction process. A model where the first stage
      of the ITC curve represent an initial polyelectrolyte complexation stage followed
      by aggregation on further titration of chitosan to the xanthan is suggested.
      Ultrastructure images by applying atomic force microscopy at some selected
      extents of titration are consistent with the two-stage interpretation of the
      thermodynamic data.

PMID- 21732324
TI  - Hydrodynamic deformation and removal of Staphylococcus epidermidis biofilms
      treated with urea, chlorhexidine, iron chloride, or DispersinB.
AB  - The force-deflection and removal characteristics of bacterial biofilm were
      measured by two different techniques before and after chemical, or enzymatic,
      treatment. The first technique involved time lapse imaging of a biofilm grown in
      a capillary flow cell and subjected to a brief shear stress challenge imparted
      through increased fluid flow. Biofilm removal was determined by calculating the
      reduction in biofilm area from quantitative analysis of transmission images. The
      second technique was based on micro-indentation using an atomic force microscope.
      In both cases, biofilms formed by Staphylococcus epidermidis were exposed to
      buffer (untreated control), urea, chlorhexidine, iron chloride, or DispersinB. In
      control experiments, the biofilm exhibited force-deflection responses that were
      similar before and after the same treatment. The biofilm structure was stable
      during the post-treatment shear challenge (1% loss). Biofilms treated with
      chlorhexidine became less deformable after treatment and no increase in biomass
      removal was seen during the post-treatment shear challenge (2% loss). In
      contrast, biofilms treated with urea or DispersinB became more deformable and
      exhibited significant biofilm loss during the post-treatment flow challenge (71%
      and 40%, respectively). During the treatment soak phase, biofilms exposed to urea
      swelled. Biofilms exposed to iron chloride showed little difference from the
      control other than slight contraction during the treatment soak. These
      observations suggest the following interpretations: (1) chemical or enzymatic
      treatments, including those that are not frankly antimicrobial, can alter the
      cohesion of bacterial biofilm; (2) biocidal treatments (e.g., chlorhexidine) do
      not necessarily weaken the biofilm; and (3) biofilm removal following treatment
      with agents that make the biofilm more deformable (e.g., urea, DispersinB) depend
      on interaction between the moving fluid and the biofilm structure. Measurements
      such as those reported here open the door to development of new technologies for
      controlling detrimental biofilms by targeting biofilm cohesion rather than
      killing microorganisms.

PMID- 21732325
TI  - Development of hybrid baculovirus vectors for artificial MicroRNA delivery and
      prolonged gene suppression.
AB  - MicroRNA (miRNA) plays essential roles in regulating gene expression, but miRNA
      delivery remains a hurdle, thus entailing a vector system for efficient transfer.
      Baculovirus emerges as a promising gene delivery vector but its inherent
      transient expression restricts its applications in some scenarios. Therefore,
      this study primarily aimed to develop baculovirus as a miRNA expression vector
      for prolonged gene suppression. We constructed recombinant baculoviruses carrying
      artificial egfp-targeting miRNA sequences within the miR155 backbone, which after
      expression by the cytomegalovirus promoter could knockdown the enhanced green
      fluorescent protein (EGFP) expression in a sequence- and dose-dependent manner.
      By swapping the mature miRNA sequences, the baculovirus miRNA shuttle effectively
      repressed the overexpression of endogenous TNF-alpha in arthritic synoviocytes
      without inducing apoptosis. To prolong the baculovirus-mediated expression, we
      further developed a hybrid baculovirus vector that exploited the Sleeping Beauty
      (SB) transposon for gene integration and sustained miRNA expression. The hybrid
      baculovirus vector that combined the miR155 scaffold and SB transposon
      effectively repressed the transgene expression for a prolonged period of time,
      hence diversifying the applications of baculovirus to indications necessitating
      prolonged gene regulation such as arthritis.

PMID- 21732326
TI  - Cell surface display of carbonic anhydrase on Escherichia coli using ice
      nucleation protein for CO2 sequestration.
AB  - Carbonic anhydrase (CA) has recently gained renewed interests for its potential
      as a mass-transfer facilitator for CO(2) sequestration. However, the low
      stability and high price severely limit its applications. In this work, the
      expression of alpha-CA from Helicobacter pylori on the outer membrane of
      Escherichia coli using a surface-anchoring system derived from ice nucleation
      protein (INP) from Pseudomonas syringae was developed. To find the best surface
      anchoring motif, full-length INP (114 kDa), truncated INP (INP-NC, 33 kDa), and
      INP's N-domain with first two subunits (INP-N, 22 kDa) were evaluated. Two
      vectors, pKK223-3 and pET22b(+), with different promoters (T7 and Tac) were used
      to construct the fusion genes, and for each vector, three recombinant strains,
      each expressing a different length of the fusion protein, were obtained. SDS
      PAGE, Western blot, immunofluorescence microscopy, FACS, and whole-cell ELISA
      confirmed the expression of fusion proteins on the surface of E. coli. The
      smallest fusion protein with INP-N as the anchoring motif had the highest
      expression level and CA activity, suggesting that INP-N is the best carrying
      protein due to its smaller size. Also, the T7 promoter in pET22b(+) induced with
      0.2 mM IPTG gave high protein expression levels, whereas the Tac promoter in
      pKK223-3 gave low expression levels. The surface displayed CA was at least
      twofold more stable than that of the free form, and did not show any adverse
      effect on cell growth and outer membrane integrity. Cells with surface displayed
      CA were successfully used to facilitate CO(2) sequestration in contained liquid
      membrane (CLM).

PMID- 21732327
TI  - A new fluorescence complementation biosensor for detection of estrogenic
      compounds.
AB  - Estrogenic compounds are an important class of hormonal substances that can be
      found as environmental contaminants, with sources including pharmaceuticals,
      human and animal waste, the chemical industry, and microbial metabolism. Here we
      report the creation of a biosensor useful for monitoring such compounds, based on
      complementation of fluorescent protein fragments. A series of sensors were made
      consisting of fragments of a split mVenus fluorescent protein fused at several
      different N-terminal and C-terminal positions flanking the ligand binding domain
      of the estrogen receptor alpha. When expressed in HeLa cells, sensor 6 (ERalpha
      312-595) showed a nine-fold increase in fluorescence in the presence of estrogen
      receptor agonists or antagonists. Sensor 2 (ERalpha 281-549) discriminated
      between agonists and antagonists by showing a decrease in fluorescence in the
      presence of agonists while being induced by antagonists. The fluorescent signal
      of sensor 6 increased over a period of 24 h, with a two-fold induction visible at
      4 h and four-fold at 8 h of ligand incubation. Ligand titration showed a good
      correlation with the known relative binding affinities of the compound. The
      sensor could detect a number of compounds of interest that can act as
      environmental endocrine disruptors. The lack of a substrate requirement, the
      speed of signal development, the potential for high throughput assays, and the
      ability to distinguish agonists from antagonists make this an attractive sensor
      for widespread use.

PMID- 21732328
TI  - Physical degradation of proteins in well-defined fluid flows studied within a
      four-roll apparatus.
AB  - In most applications of biotechnology and downstream processing proteins are
      exposed to fluid stresses in various flow configurations which often lead to the
      formation of unwanted protein aggregates. In this paper we present physical
      degradation experiments for proteins under well-defined flow conditions in a four
      roll apparatus. The flow field was characterized numerically by computational
      fluid dynamics (CFD) and experimentally by particle image velocimetry (PIV). The
      local shear strain rate as well as the local shear and elongation rate was used
      to characterize the hydrodynamic stress environment acting on the proteins.
      Lysozyme was used as a model protein and subjected to well-defined fluid stresses
      in high and low stress environment. By using in situ turbidity measurements
      during stressing the aggregate formation was monitored directly in the fluid
      flow. An increase in absorbance at 350 nm was attributed to a higher content of
      visible particles (>1 um). In addition to lysozyme, the formation of aggregates
      was confirmed for two larger proteins (bovine serum albumin and alcohol
      dehydrogenase). Thus, the presented experimental setup is a helpful tool to
      monitor flow-induced protein aggregation with high reproducibility. For instance,
      screening experiments for formulation development of biopharmaceuticals for fill
      and finish operations can be performed in the lab-scale in a short time-period if
      the stress distributions in the application are transferred and applied in the
      four-roll mill.

PMID- 21732329
TI  - Tuning structural durability of yeast-encapsulating alginate gel beads with
      interpenetrating networks for sustained bioethanol production.
AB  - Microorganisms have become key components in many biotechnological processes to
      produce various chemicals and biofuels. The encapsulation of microbial cells in
      calcium cross-linked alginate gel beads has been extensively studied due to
      several advantages over using free cells. However, industrial use of alginate gel
      beads has been hampered by the low structural stability of the beads. In this
      study, we demonstrate that the incorporation of interpenetrating covalent cross
      links in an ionically cross-linked alginate gel bead significantly enhances the
      bead's structural durability. The interpenetrating network (IPN) was prepared by
      first cross-linking alginate chemically modified with methacrylic groups, termed
      methacrylic alginate (MA), with calcium ions and subsequently conducting a photo
      cross-linking reaction. The resulting methacrylic alginate gel beads (IPN-MA)
      exhibited higher stiffness, ultimate strength and ultimate strain and also
      remained more stable in media either subjected to high shear or supplemented with
      chelating agents than calcium cross-linked alginate gel beads. Furthermore, yeast
      cells encapsulated in IPN-MA gel beads remained more metabolically active in
      ethanol production than those in calcium cross-linked alginate gel beads.
      Overall, the results of this study will be highly useful in designing
      encapsulation devices with improved structural durability for a broad array of
      prokaryotic and eukaryotic cells used in biochemical and industrial processes.

PMID- 21732330
TI  - Engineering the pentose phosphate pathway to improve hydrogen yield in
      recombinant Escherichia coli.
AB  - Among various routes for the biological hydrogen production, the NAD(P)H
      dependent pentose phosphate (PP) pathway is the most efficient for the dark
      fermentation. Few studies, however, have focused on the glucose-6-phosphate 1
      dehydrogenase, encoded by zwf, as a key enzyme activating the PP pathway.
      Although the gluconeogenic activity is essential for activating the PP pathway,
      it is difficult to enhance the NADPH production by regulating only this activity
      because the gluconeogenesis is robust and highly sensitive to concentrations of
      glucose and AMP inside the cell. In this study, the FBPase II (encoded by glpX),
      a regulation-insensitive enzyme in the gluconeogenic pathway, was activated.
      Physiological studies of several recombinant, ferredoxin-dependent hydrogenase
      system-containing Escherichia coli BL21(DE3) strains showed that overexpression
      of glpX alone could increase the hydrogen yield by 1.48-fold compared to a strain
      with the ferredoxin-dependent hydrogenase system only; the co-overexpression of
      glpX with zwf increased the hydrogen yield further to 2.32-fold. These results
      indicate that activation of the PP pathway by glpX overexpression-enhanced
      gluconeogenic flux is crucial for the increase of NAD(P)H-dependent hydrogen
      production in E. coli BL21(DE3).

PMID- 21732331
TI  - Optimization of flowrate for expansion of human embryonic stem cells in perfusion
      microbioreactors.
AB  - Microfluidic systems create significant opportunities to establish highly
      controlled microenvironmental conditions for screening pluripotent stem cell
      fate. However, since cell fate is crucially dependent on this microenvironment,
      it remains unclear as to whether continual perfusion of culture medium supports
      pluripotent stem cell maintenance in feeder-free, chemically defined conditions,
      and further, whether optimum perfusion conditions exist for subsequent use of
      human embryonic stem cell (hESCs) in other microfludic systems. To investigate
      this, we designed microbioreactors based on resistive flow to screen hESCs under
      a linear range of flowrates. We report that at low rates (conditions where
      glucose transport is convection-limited with Peclet number <1), cells are
      affected by apparent nutrient depletion and waste accumulation, evidenced by
      reduced cell expansion and altered morphology. At higher rates, cells are
      spontaneously washed out, and display morphological changes which may be
      indicative of early-stage differentiation. However, between these thresholds
      exists a narrow range of flowrates in which hESCs expand comparably to the
      equivalent static culture system, with regular morphology and maintenance of the
      pluripotency marker TG30 in >95% of cells over 7 days. For MEL1 hESCs the optimum
      flowrate also coincided with the time-averaged medium exchange rate in static
      cultures, which may therefore provide a good first estimate of appropriate
      perfusion rates. Overall, we demonstrate hESCs can be maintained in
      microbioreactors under continual flow for up to 7 days, a critical outcome for
      the future development of microbioreactor-based screening systems and assays for
      hESC culture.

PMID- 21732333
TI  - The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm.
AB  - The use of tyrosine kinase inhibitors (TKIs) has become an integral component of
      cancer therapy. Imatinib mesylate, a breakpoint cluster region-Abelson BCR-ABL1
      inhibitor, was the first TKI approved in cancer medicine and has served as a
      model for the development of similar agents for other cancers. An important
      drawback of TKI therapy is the development of resistance, frequently through the
      acquisition of mutations. Mutations at the gatekeeper residues of BCR-ABL1 (eg,
      the threonine-to-isoleucine mutation at codon 315) and other oncogenic kinases
      have proven highly resistant to currently available TKIs. Advances in the
      structural biology of oncogenic kinases have facilitated the rational development
      of TKIs that are active against gatekeeper mutations.

PMID- 21732332
TI  - Prediction models in cancer care.
AB  - Prediction is ubiquitous across the spectrum of cancer care from screening to
      hospice. Indeed, oncology is often primarily a prediction problem; many of the
      early stage cancers cause no symptoms, and treatment is recommended because of a
      prediction that tumor progression would ultimately threaten a patient's quality
      of life or survival. Recent years have seen attempts to formalize risk prediction
      in cancer care. In place of qualitative and implicit prediction algorithms, such
      as cancer stage, researchers have developed statistical prediction tools that
      provide a quantitative estimate of the probability of a specific event for an
      individual patient. Prediction models generally have greater accuracy than
      reliance on stage or risk groupings, can incorporate novel predictors such as
      genomic data, and can be used more rationally to make treatment decisions.
      Several prediction models are now widely used in clinical practice, including the
      Gail model for breast cancer incidence or the Adjuvant! Online prediction model
      for breast cancer recurrence. Given the burgeoning complexity of diagnostic and
      prognostic information, there is simply no realistic alternative to incorporating
      multiple variables into a single prediction model. As such, the question should
      not be whether but how prediction models should be used to aid decision-making.
      Key issues will be integration of models into the electronic health record and
      more careful evaluation of models, particularly with respect to their effects on
      clinical outcomes.

PMID- 21732334
TI  - Does "in situ lymphoma" occur as a distinct step in the development of nodular
      lymphocyte-predominant Hodgkin lymphoma?
AB  - The concept of in situ neoplasia, already well acknowledged in epithelial tumors,
      has now been extended to lymphoid neoplasms. Among germinal center (GC)-derived
      lymphomas, a type of "in situ follicular lymphoma (FL)" has been described in
      which cells that strongly express BCL2 are observed in histologically abnormal
      follicles. In this commentary, the author suggests that another GC-derived
      lymphoma, ie, nodular lymphocyte-predominant Hodgkin lymphoma with a micronodular
      pattern in which small GCs or broken-up GCs are present within nodules, may be
      regarded as an early lesion limited to GC. Like "in situ FL," this is likely to
      be an in situ step that potentially leads to overt lymphoma.

PMID- 21732335
TI  - Preoperative chemotherapy for bladder cancer: a standard waits to be optimally
      deployed.

PMID- 21732336
TI  - Use of human papillomavirus vaccines among young adult women in the United
      States: an analysis of the 2008 National Health Interview Survey.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommends catch-up
      administration of human papillomavirus (HPV) vaccines to girls and women ages 13
      to 26 who have not been vaccinated previously. In response to debate regarding
      catch-up vaccination of young adult women, this study examined whether 18- to 26
      year-old women most likely to benefit from catch-up vaccination were aware of the
      HPV vaccine, and initiated the vaccine series by the end of 2008. METHODS: We
      used data from the 2008 National Health Interview Survey to assess HPV vaccine
      awareness and use, and reasons for not vaccinating, among women aged 18-26 years
      (n = 1583). Sociodemographic, health care access, and health history factors
      associated with vaccine initiation were assessed using multivariate logistic
      regression. RESULTS: Overall, 11.7% of women aged 18-26 years reported receiving
      at least 1 dose of the HPV vaccine by the end of 2008. In multivariate analyses,
      younger age, history of previous HPV infection, unmarried status, health
      insurance, flu shot in the past year, and receipt of 1 or more recommended
      lifetime vaccines were significantly associated with HPV vaccine initiation. Two
      fifths (39.6%) of unvaccinated women were interested in receiving the HPV vaccine
      (n = 1327). Primary reasons for lack of interest in the vaccine were belief that
      it was not needed, not knowing enough about it, concerns about safety, and not
      being sexually active. CONCLUSION: HPV vaccine coverage among young adult women
      was low, and lower among the uninsured than the insured. Public financing and
      care provision programs have the potential to expand vaccine coverage among
      uninsured women, who are at increased risk of cervical cancer.

PMID- 21732337
TI  - Expanding Nilotinib Access in Clinical Trials (ENACT): an open-label, multicenter
      study of oral nilotinib in adult patients with imatinib-resistant or imatinib
      intolerant Philadelphia chromosome-positive chronic myeloid leukemia in the
      chronic phase.
AB  - BACKGROUND: Nilotinib is a selective, potent BCR-ABL inhibitor. Previous studies
      demonstrated the efficacy and safety of nilotinib in Philadelphia chromosome
      positive chronic myeloid leukemia patients in chronic phase (CML-CP) or
      accelerated phase who failed prior imatinib. METHODS: This expanded access trial
      further characterized the safety of nilotinib 400 mg twice daily in patients with
      CML-CP (N = 1422). RESULTS: In this large, heavily pretreated population,
      nilotinib demonstrated significant efficacy, with complete hematologic response
      and complete cytogenetic response achieved in 43% and 34% of patients,
      respectively. Responses were rapid, mostly occurring within 6 months, and were
      higher in patients with suboptimal response to imatinib, with 75% and 50%
      achieving major cytogenetic response and complete cytogenetic response,
      respectively. At 18 months, the progression-free survival rate was 80%. Most
      patients achieved planned dosing of 400 mg twice daily and maintained the dose
      >12 months. Nonhematologic adverse events (AEs) were mostly mild to moderate and
      included rash (28%), headache (25%), and nausea (17%). Grade 3 or 4
      thrombocytopenia (22%), neutropenia (14%), and anemia (3%) were low and managed
      by dose reduction or brief interruption. Grade 3 or 4 elevations in serum
      bilirubin and lipase occurred in 4% and 7% of patients, respectively. The
      incidence of newly occurring AEs decreased over time. Of patients who experienced
      a dose reduction because of AEs and attempted a re-escalation, 87% successfully
      achieved re-escalation to the full dose. CONCLUSIONS: This large study confirms
      that nilotinib was well tolerated and that grade 3 or 4 AEs occurred infrequently
      and were manageable through transient dose interruptions.

PMID- 21732338
TI  - Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia:
      an effective but myelosuppressive regimen to be offered to patients with advanced
      disease.
AB  - BACKGROUND: The combination of fludarabine, cyclophosphamide, and rituximab (FCR)
      has produced promising results in chronic lymphocytic leukemia and other
      lymphoproliferative disorders. The authors report the final results from a
      multicenter, prospective study examining FCR in Waldenstrom macroglobulinemia
      (WM). METHODS: Forty-three patients with symptomatic WM that was untreated or
      pretreated with 1 line of chemotherapy received rituximab 375 mg/m(2)
      intravenously on day 1 and fludarabine 25 mg/m(2) and cyclophosphamide 250
      mg/m(2) intravenously on days 2 through 4. FCR was repeated every 28 days for up
      to 6 courses. RESULTS: The overall response rate was 79%, and the major response
      rate of 74.4%, including 11.6% complete remissions (CRs) and 20.9% very good
      partial remissions. An amelioration of the quality of responses was observed
      during follow-up, leading to 18.6% of CRs. No differences in terms of responses
      were observed among previously treated or untreated patients. Among the clinical
      and laboratory features that were considered, only the beta2-microglobulin level
      had a significant impact in terms of achieving a major response. The major
      toxicity reported was grade 3/4 neutropenia, which occurred in 45% of courses and
      was the main reason for treatment discontinuation. After the end of treatment, 19
      patients (44%) had long-lasting episodes of neutropenia. Three patients developed
      myelodysplastic syndrome during follow-up. CONCLUSIONS: The FCR regimen was
      capable of neutralizing adverse prognostic factors and proved to be active in
      patients with WM, leading to rapid disease control and good-quality responses.
      Because myelosuppression was the main concern, further studies are warranted to
      optimize dosages and treatment duration.

PMID- 21732339
TI  - Clinically significant Gleason sum upgrade: external validation and head-to-head
      comparison of the existing nomograms.
AB  - BACKGROUND: Several nomograms have been developed for the purpose of predicting
      the likelihood of an increase in Gleason sum (GS) from biopsy information
      compared with the GS determined after examination of the "entire prostate" in
      patients with prostate cancer. In this study, the authors evaluated and compared
      the ability of 4 nomograms (published by Capitanio et al, Chun et al, Kulkarni et
      al, and Moussa et al) to predict GS upgrades for patients with biopsy GS <=6
      prostate cancer who underwent radical prostatectomy (RP) at their center.
      METHODS: The entire study cohort included 942 patients with a biopsy GS <=6.
      Predictive performances of the nomograms were compared using area under the
      receiver operating characteristic curve (AUC-ROC) analysis, calibration plots,
      and decision curve analysis (DCA) in the entire cohort, in patients with low-risk
      prostate cancer (LRPC), and a subgroup of those patients who underwent extended
      biopsy with >=10 cores. RESULTS: Patients with a GS >=7 at prostatectomy included
      319 of 942 patients (33.9%) in the entire study cohort, 263 of 814 patients
      (32.2%) with LRPC, and 84 of 301 patients (27.9%) with LRPC who underwent
      extended biopsy. With an AUC-ROC of 0.637 to 0.647 in the different subgroups of
      patients with low-risk cancer, the Kulkarni et al nomogram demonstrated
      significantly higher discriminative ability compared with the other nomograms.
      The same nomogram provided a small clinical benefit at DCA. All nomograms were
      poorly calibrated. CONCLUSIONS: The available prognostic tools had limited
      ability to predict clinically significant upgrading in patients with biopsy GS
      <=6 and, thus, the authors concluded that these tools are not ready for clinical
      application.

PMID- 21732340
TI  - Urinary acylcarnitines are altered in human kidney cancer.
AB  - Kidney cancer often diagnosed at late stages when treatment options are severely
      limited. Thus, greater understanding of tumor metabolism leading ultimately to
      novel approaches to diagnosis is needed. Our laboratory has been utilizing
      metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids
      at concentrations different from control patients. Here, we collected urine
      samples from kidney cancer patients and analyzed them by chromatography coupled
      to mass spectrometry. Once normalized to control for urinary concentration,
      samples were analyzed by two independent laboratories. After technical
      validation, we now show differential urinary concentrations of several
      acylcarnitines as a function of both cancer status and kidney cancer grade, with
      most acylcarnitines being increased in the urine of cancer patients and in those
      patients with high cancer grades. This finding was validated in a mouse xenograft
      model of human kidney cancer. Biological validation shows carbon chain length
      dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher
      chain length acylcarnitines demonstrated inhibitory effects on NF-kappaB
      activation, suggesting an immune modulatory effect of these compounds. Thus,
      acylcarnitines in the kidney cancer urine may reflect alterations in metabolism,
      cell component synthesis and/or immune surveillance, and may help explain the
      profound chemotherapy resistance seen with this cancer. This study shows for the
      first time the value of a novel class of metabolites which may lead to new
      therapeutic approaches for cancer and may prove useful in cancer biomarker
      studies. Furthermore, these findings open up a new area of investigation into the
      metabolic basis of kidney cancer.

PMID- 21732341
TI  - Biomarkers predicting development of metachronous gastric cancer after endoscopic
      resection: an analysis of molecular pathology of Helicobacter pylori eradication.
AB  - Metachronous gastric cancer (MGC) after endoscopic resection (ER) of gastric
      cancer still occurs to some degree even after Helicobacter pylori (H. pylori)
      treatment. We evaluated whether two biomarkers related to carcinogenesis
      expressed in intestinal metaplasia (IM) become predictors for MGC development
      after eradication. We performed a hospital-based, case-control study of 75
      patients, including 50 mucosal cancer patients who had undergone ER (Group DYS),
      and 25 age- and sex-matched chronic gastritis patients for whom H. pylori had
      been successfully eradicated (control). Additionally, Group DYS patients were
      divided into two groups: 25 successfully H. pylori-eradicated (eradicated group)
      and 25 un-eradicated patients (persistent group). All patients were followed for
      1 year. We analyzed microsatellite instability (MSI) and immunoperoxidase assays
      using a monoclonal antibody for the colonic phenotype (Das-1). Both MSI and Das-1
      reactivity in IM were significantly higher in Group DYS than in the control (p <
      0.05 and p < 0.01, respectively). MSI and Das-1 reactivity were strong and
      independent predictors for gastric cancer (OR = 7.09, 95% CI 1.27-39.6, p = 0.03
      for MSI and OR = 4.96, 95% CI 1.64-15.0, p = 0.005 for Das-1 reactivity). The
      incidence of MSI tended to decrease in the eradicated group (p = 0.07), but not
      in the persistent group. The Das-1 immunoreactivity in IM also declined in both
      the eradicated group and the control. Interestingly, all MGCs after ER were
      positive for MSI or Das-1 reactivity. MSI or Das-1 reactivity in IM strongly
      predicts the development of MGC. Patients in whom these biomarkers persist after
      eradication may therefore have a high risk of developing MGC.

PMID- 21732342
TI  - Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in
      erlotinib-resistant NSCLC and other EGFR-dependent cancer models.
AB  - The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases
      has been implicated in a variety of cancers. In particular, activating mutations
      such as the L858R point mutation in exon 21 and the small in-frame deletions in
      exon 19 of the EGFR tyrosine kinase domain are correlated with sensitivity to
      EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) patients.
      Clinical treatment of patients is limited by the development of drug resistance
      resulting mainly from a gatekeeper mutation (T790M). In this study, we evaluated
      the therapeutic potential of a novel, irreversible pan-HER inhibitor, HM781-36B.
      The results from this study show that HM781-36B is a potent inhibitor of EGFR in
      vitro, including the EGFR-acquired resistance mutation (T790M), as well as HER-2
      and HER-4, compared with other EGFR tyrosine kinases inhibitors (erlotinib,
      lapatinib and BIBW2992). HM781-36B treatment of EGFR DelE746_A750-harboring
      erlotinib-sensitive HCC827 and EGFR L858R/T790M-harboring erlotinib-resistant NCI
      H1975 NSCLC cells results in the inhibition of EGFR phosphorylation and the
      subsequent deactivation of downstream signaling proteins. Additionally, HM781-36B
      shows an excellent efficacy in a variety of EGFR- and HER-2-dependent tumor
      xenograft models, including erlotinib-sensitive HCC827 NSCLC cells, erlotinib
      resistant NCI-H1975 NSCLC cells, HER-2 overexpressing Calu-3 NSCLC cells, NCI-N87
      gastric cancer cells, SK-Ov3 ovarian cancer cells and EGFR-overexpressing A431
      epidermoid carcinoma cancer cells. On the basis of these preclinical results,
      HM781-36B is the most potent pan-HER inhibitor, which will be advantageous for
      the treatment of patients with NSCLC including clinical limitation caused by
      acquired mutation (EGFR T790M), breast cancer and gastric cancer.

PMID- 21732343
TI  - ETS-1/RhoC signaling regulates the transcription factor c-Jun in melanoma.
AB  - Recently, we discovered that the loss of E-cadherin induces c-Jun protein
      expression, which is a member of the AP-1 transcription factor family and a key
      player in the processes of cell proliferation and tumor development and also
      found in elevated levels in melanomas. Notably, the mRNA level of c-Jun was not
      affected, suggesting that c-Jun is regulated at post-transcriptional level. Here,
      we present data that suggest that the dynamic cytoskeletal network, linked to E
      cadherin, is involved in the regulation of the c-Jun protein and transcriptional
      activity. In a signaling cascade, the loss of E-cadherin activates the
      transcriptional regulator ETS-1 and consequently leads to the induction of RhoC
      expression that stabilizes c-Jun in melanoma. The link between RhoC and c-Jun
      seems to be indirect via the cytoskeleton. We conclude that the loss of E
      cadherin mediated cell-adhesion induces c-Jun protein expression in a multistep
      process, offering several possibilities for therapeutic intervention.

PMID- 21732344
TI  - Human adipose tissue-derived mesenchymal stem cells expressing yeast
      cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat
      glioblastoma.
AB  - Prodrug cancer gene therapy by mesenchymal stem cells (MSCs) targeted to tumors
      represents an attractive tool to activate prodrugs directly within the tumor
      mass, thus avoiding systemic toxicity. In this study, we tested the feasibility
      and efficacy of human adipose tissue-derived MSCs, engineered to express the
      suicide gene cytosine deaminase::uracil phosphoribosyltransferase to treat
      intracranial rat C6 glioblastoma. Experiments were designed to simulate
      conditions of future clinical application for high-grade glioblastoma therapy by
      direct injections of therapeutic stem cells into tumor. We demonstrated that
      genetically modified therapeutic stem cells still have the tumor tropism when
      injected to a distant intracranial site and effectively inhibited glioblastoma
      growth after 5-fluorocytosine (5-FC) therapy. Coadministration of C6 cells and
      therapeutic stem cells with delayed 5-FC therapy improved the survival in a
      therapeutic stem cell dose-dependent manner and induced complete tumor regression
      in a significant number of animals. Continuous intracerebroventricular delivery
      of 5-FC using osmotic pump reduced the dose of prodrug required for the same
      therapeutic effect, and along with repeated administration of therapeutic stem
      cells increased the survival time. Intracerebral injection of therapeutic stem
      cells and treatment with 5-FC did not show any detectable adverse effects.
      Results support the arguments to begin clinical studies for treatment of high
      grade brain tumors.

PMID- 21732345
TI  - Inecalcitol, an analog of 1alpha,25(OH)(2) D(3) , induces growth arrest of
      androgen-dependent prostate cancer cells.
AB  - 19-nor-14-epi-23-yne-1,25(OH)(2) D(3)  (inecalcitol) is a unique vitamin D(3) 
      analog. We evaluated the activity of inecalcitol in a human prostate cancer model
      system. The analog was 11-fold more potent than 1,25(OH)(2) D(3)  in causing 50%
      clonal growth inhibition of androgen-sensitive human prostate cancer LNCaP cells.
      Inecalcitol, more than 1,25(OH)(2) D(3) , reduced in a dose-dependent manner the
      expression levels of the transcription factor ETS variant 1 and the
      serine/threonine protein kinase Pim-1, both of which are upregulated in prostate
      cancer. Remarkably, dose challenge experiments revealed that inecalcitol maximal
      tolerated dose (MTD) by intraperitoneal (i.p.) administration was 30 MUg/mouse
      (1,300 MUg/kg) three times per week, while we previously found that the MTD of
      1,25(OH)(2) D(3)  is 0.0625 MUg/mouse; therefore, inecalcitol is 480 times less
      hypercalcemic than 1,25(OH)(2) D(3) . Pharmacokinetic studies showed that plasma
      half-life of inecalcitol were 18.3 min in mice. A xenograft model of LNCaP cells
      was developed in immunodeficient mice treated with inecalcitol. The tumors of the
      diluent-treated control mice increased in size but those in the inecalcitol
      treatment group did not grow. Our data suggest that inecalcitol inhibits androgen
      responsive prostate cancer growth in vivo and should be examined either alone or
      with other chemotherapy in clinical trials in individuals with rising serum
      prostate-specific antigen after receiving either surgery or irradiation therapy
      with curative intent.

PMID- 21732346
TI  - Breast cancer incidence trends in Norway--explained by hormone therapy or
      mammographic screening?
AB  - A decline in breast cancer incidence has been observed in several countries after
      2002. Reduced use of menopausal hormonal therapy (HT), as a consequence of the
      publication of results from the Women's Health Initiative, has been argued to be
      the main reason. In Norway, the governmentally funded Norwegian Breast Cancer
      Screening Program (NBCSP) was implemented during the same time period as the
      increased use of HT. This study investigated trends in breast cancer incidence by
      use of HT and introduction of the screening program. We obtained rates of breast
      cancer from the Cancer Registry of Norway and sales data of HT preparations from
      the Norwegian Institute of Public Health. Mammography rates were estimated from
      published reports. Breast cancer incidence rates increased steadily from 1956 to
      the end of the 20th century, particularly in women aged 55-69 during 1996-2002
      residing in the counties where the NBCSP was first introduced. The rates declined
      after 2002-2003. HT use increased in 1987-2001, peaking around year 2000. In
      particular, sales of combined estrogen and progestogen preparations declined
      after 2002. Among women aged 55-59, rates of hormone receptor positive breast
      cancers peaked in 2000-2003. No such trend was seen in other age groups. In
      conclusion, the interpretation of breast cancer incidence trends in Norway from
      1987 to 2009 is complicated because the NBCSP was introduced during a period with
      increasing HT use. Both factors likely contributed to the observed trends, and
      the role of each may vary across age groups.

PMID- 21732347
TI  - The critical role of JNK in the ER-mitochondrial crosstalk during apoptotic cell
      death.
AB  - Apoptosis or programmed cell death is an extremely coordinated phenomenon that
      involves the participation of a complex interacting crosstalk between the
      endoplasmic reticulum and mitochondria. This involves a series of signaling
      molecules like stress kinases, caspases, Bcl-2 family of proteins, etc. that
      coordinately induce apoptosis by releasing apoptotic proteins from the
      mitochondria and mediate DNA damage of the cell. Among the stress kinases, JNK, a
      member of the MAPK family has been believed to be critically mediating these
      apoptotic phenomena. The involvement of JNK has been clouded by controversies
      because of its role both as a pro-apoptotic and an anti-apoptotic mediator. A
      very significant initiator of JNK activation is the pro-inflammatory cytokine, IL
      1beta, levels of which are significantly elevated in varied diseases especially
      diabetes where it is believed to significantly contribute to pancreatic beta-cell
      death. During apoptotic cell death, the endoplasmic reticulum and the
      mitochondrion participate in a relay of cellular events that determine the onset
      of the classical apoptotic pathways. Here we discuss the details of this ER
      mitochondrial crosstalk and the role of JNK herein that ultimately culminates
      into apoptotic cell death that is evident in various pathophysiological
      conditions.

PMID- 21732348
TI  - mda-7/IL-24 differentially regulates soluble and nuclear clusterin in prostate
      cancer.
AB  - Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), a unique
      member of the IL-10 gene family, displays a broad range of antitumor properties
      including cancer-specific induction of apoptosis, inhibition of tumor
      angiogenesis, and modulation of anti-tumor immune responses. Here, we identify
      clusterin (CLU) as a MDA-7/IL-24 interacting protein in DU-145 cells and
      investigate the role of MDA-7/IL-24 in regulating CLU expression and mediating
      the antitumor properties of mda-7/IL-24 in prostate cancer. Ad.mda-7 decreased
      expression of soluble CLU (sCLU) and increased expression of nuclear CLU (nCLU).
      In the initial phase of Ad.mda-7 infection sCLU expression increased and CLU
      interacted with MDA-7/IL-24 producing a cytoprotective effect. Infection of
      stable clones of DU-145 prostate cancer cells expressing sCLU with Ad.mda-7
      resulted in generation of nCLU that correlated with decreased cell viability and
      increased apoptosis. In the presence of mda-7/IL-24, sCLU-DU-145 cells displayed
      G(2)/M phase arrest followed by apoptosis. Similarly, Ad.mda-7 infection
      decreased cell migration by altering cytoskeleton in sCLU-DU-145 cells. Ad.mda-7
      treated sCLU-DU-145 cells displayed a significant reduction in tumor growth in
      mouse xenograft models and reduced angiogenesis when compared to the vector
      control group. Tumor tissue lysates demonstrated enhanced nCLU generated from
      sCLU with increased apoptosis in the presence of MDA-7/IL-24. Our findings reveal
      novel aspects relative to the role of sCLU/nCLU in regulating the anticancer
      properties of MDA-7/IL-24 that may be exploited for developing enhanced therapies
      for prostate cancer.

PMID- 21732349
TI  - Role of insulin-like growth factors (IGFs), their receptors and genetic
      regulation in the chondrogenesis and growth of the mandibular condylar cartilage.
AB  - Growth of the mandibular condylar cartilage (MCC) is reviewed as a function of
      genetic and epigenetic factors. The growth centers around the differential
      spatial concentration of the chondrocytes, influence of growth factors like TGF
      beta and heterogeneity in the number of IGF receptors, control the action of IGF.
      Besides these factors, growth of the mandibular condyle is influenced by
      differential response of chondrocytes as a function of their source/ageing, which
      in turn is regulated by TGF-beta, BMPs and IGFs. While IGF-1 promotes
      proteoglycan synthesis and survival of the chondrocytes to maintain cartilage
      homeostasis, TGF-beta synergistically catalysed the effect of IGF-1, while BMPs
      catalysed proteolysis as and when physiologically needed. To understand these
      processes, role of IGF-1 and its six receptors is at the center to a number of
      physiological processes being regulated by its mode of application for the growth
      and differentiation. Probing deeper, biological functions of IGFs seemed to
      depend on their level of free status rather than bound status to respective IGF
      binding proteins (IGF-BPs), considered prerequisite to modulate their biological
      functions. Genetic regulation of their secretion has thrown light on their
      insulin-like structural homology, level and response in osteo-arthritis (OA),
      rheumatic arthritis (RA) and diabetes type-II. Biochemistry and spatial
      distribution of IGF receptors in different domains exerts control on IGF-1
      activities. In ultimate analysis, IGF-axis conserved during the evolution to
      regulate cell growth and proliferation affect nearly every organ in the body as
      judged from the techniques determining skeletal maturity and decision making
      dependent on it for orthodontic, orthognathic/orthopedic and dental implant
      applications.

PMID- 21732350
TI  - Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a
      caspase-3- and caspase-9-dependent mitochondrial signaling pathway.
AB  - Zearalenone is a mycotoxin produced mainly by Fusarium. There are numerous
      incidences of mycotoxicosis in laboratory and domestic animals, especially in
      pigs. However, little is known about molecular mechanisms of zearalenone
      toxicity. Granulosa cells are the maximal cell population in follicles, and they
      play an essential role in the development and maturation of follicles. The
      objective of this study was to explore the effect of zearalenone at high
      concentrations on proliferation and apoptosis of porcine granulosa cells and
      uncover signaling pathway underlying the cytotoxicity of zearalenone. We found
      that zearalenone reduced the proliferation of porcine granulosa cells in a dose
      dependent manner as shown by the MTT assay and zearalenone resulted in an obvious
      apoptosis and necrosis in porcine granulosa cells as determined by the TUNEL
      analysis and flow cytometry. In addition, TUNEL assay with caspase inhibitors
      showed that zearalenone triggered a caspase-3- and caspase-9-dependent apoptotic
      process in porcine granulosa cells. Fluorescence spectrophotometer displayed that
      zearalenone led to a loss of mitochondrial transmembrane potential of porcine
      granulosa cells but enhanced reactive oxygen species (ROS) levels of the cells.
      Notably, Western blots revealed that caspase-3 and caspase-9 were activated by
      zearalenone in porcine granulosa cells. Collectively, our results suggest that
      zearalenone induces apoptosis and necrosis of porcine granulosa cells in a dose
      dependent manner via a caspase-3- and caspase-9-dependent mitochondrial pathway.
      This study thus offers a novel insight into molecular mechanisms by which
      zearalenone has adverse cytotoxicity on reproduction.

PMID- 21732351
TI  - Possible role of RKIP in cytotrophoblast migration: immunohistochemical and in
      vitro studies.
AB  - Raf kinase inhibitor protein (RKIP) regulates growth and differentiation
      signaling of mitogen-activated protein kinases (MAPK), GRK2 and NF-kappaB
      pathways each of which regulates cytotrophoblast differentiation and normal
      placental development. We show here that RKIP is expressed in human normal and
      preeclampic placentas as detected by immunostaining. RKIP was detected in villous
      cytotrophoblast in normal placenta and switched to syncytiotrophoblast in pre
      eclampsia (PE)-complicated pregnancies. RKIP was also localized in extravillous
      cytotrophoblast of cell islands and cell columns both in normal and in PE
      placentas, although staining was less uniform in the latter specimens. In order
      to test RKIP involvement in cytotrophoblast function, we performed in vitro
      studies on HTR-8/SVneo cells, a first trimester cytotrophoblast cell line. We
      show that the RKIP inhibitor locostatin reduces ERK phosphorylation and impairs
      HTR-8/SV neo cells motility in wound closure experiments. We also document the
      presence of GRK2 mRNA, the reduction of phosphorylated RKIP expression by
      locostatin and the induction of PAI mRNA expression in HTR-8/SV neo cells,
      suggesting the involvement of GRK2 and NF-kappaB pathways in these cells. In
      conclusion, our work provides evidence that RKIP is a novel factor expressed in
      cytotrophoblast cells where it likely regulates cell migration.

PMID- 21732352
TI  - Mouse embryonic stem cells that survive gamma-rays exposure maintain pluripotent
      differentiation potential and genome stability.
AB  - This study aimed to investigate the cell cycle, apoptosis, cytogenetics and
      differentiation capacity of mouse embryonic stem cells (mESCs) that survived a
      single dose of 2 or 5 Gy gamma-rays during a period of up to 96 h of culture.
      After 2 Gy irradiation and 24 h culture, compared to control, a significant
      majority of cells was blocked at the G2/M phase and a massive apoptosis was
      recorded. Between 48 and 72 h post-irradiation, the parameters used to describe
      the cell cycle and apoptosis returned similar to those of control samples. When
      mESCs were irradiated with 5 Gy, a small fraction of cells, even after 96 h of
      culture, still presented clear evidences of a G2/M block and apoptosis. The
      cytogenetic analysis performed at 96 h showed that the structural stability of
      the aberrations did not change significantly when comparing control and 2 or 5 Gy
      treated populations. However, the chromosomal damage observed in the progeny of
      the survived cells after 5 Gy exposure is significantly higher than that observed
      in control samples, although it is mostly of the stable and transmissible type.
      Ninety-six hours after irradiation, the survived mESCs maintained their
      undifferentiated status and capability to differentiate into the three germ
      layers. Overall, these results indicate a commitment of mESCs to maintain
      pluripotency and genome stability.

PMID- 21732353
TI  - Dok-1 and Dok-2 deficiency induces osteopenia via activation of osteoclasts.
AB  - Osteoporosis causes fractures that lead to reduction in the quality of life and
      it is one of the most prevalent diseases as it affects approximately 10% of the
      population. One of the important features of osteoporosis is osteopenia. However,
      its etiology is not fully elucidated. Dok-1 and Dok-2 are adaptor proteins acting
      downstream of protein tyrosine kinases that are mainly expressed in the cells of
      hematopoietic lineage. Although these proteins negatively regulate immune system,
      their roles in bone metabolism are not understood. Here, we analyzed the effects
      of Dok-1 and Dok-2 double-deficiency on bone. Dok-1/2 deficiency reduced the
      levels of trabecular and cortical bone mass compared to wildtype. In addition,
      Dok-1/2 deficiency increased periosteal perimeters and endosteal perimeters of
      the mid shaft of long bones. Histomorphometric analysis of the bone parameters
      indicated that Dok-1/2 deficiency did not significantly alter the levels of bone
      formation parameters including mineralizing surface/bone surface (MS/BS), mineral
      apposition rate (MAR) and bone formation rate (BFR). In contrast, Dok-1/2
      deficiency enhanced the levels of bone resorption parameters including osteoclast
      number (N.Oc/BS) and osteoclast surface (Oc.S/BS). Analyses of individual
      osteoclastic activity indicated that Dok-1/2 deficiency enhanced pit formation.
      Systemically, Dok-1/2 deficiency increased the levels of urinary
      deoxypyridinoline (Dpyr). Search for the target point of the Dok-1/2 deficiency
      effects on osteoclasts identified that the mutation enhanced sensitivity of
      osteoclast precursors to macrophage colony-stimulating factor. These data
      revealed that Dok-1 and Dok-2 deficiency induces osteopenia by activation of
      osteoclasts.

PMID- 21732354
TI  - Activation of the p53 pathway induces alpha-smooth muscle actin expression in
      both myeloid leukemic cells and normal macrophages.
AB  - A range of cell types of mesenchymal origin express alpha-smooth muscle actin
      (alpha-SMA), a protein that plays a key role in controlling cell motility and
      differentiation along the fibrocyte and myofibroblast lineages. Although alpha
      SMA is often expressed in stromal cells associated to a variety of cancers
      including hematological malignancies, up to now the role of anti-cancer drugs on
      alpha-SMA has not been deeply investigated. In this study, we demonstrated that
      Nutlin-3, the small molecule inhibitor of the MDM2/p53 interactions,
      significantly up-regulated the mRNA and protein levels of alpha-SMA in normal
      macrophages as well as in p53(wild-type) but not in p53(mutated/null) myeloid
      leukemic cells. The p53-dependence of alpha-SMA up-regulation induced by Nutlin-3
      was demonstrated in experiments performed with siRNA for p53. Of note, Nutlin-3
      mediated up-regulation of alpha-SMA in OCI leukemic cells was accompanied by cell
      adhesion to plastic substrate and by reduced cell migratory response in transwell
      assays. Notably, the role of alpha-SMA induction in the modulation of myeloid
      cell migration was clearly documented in alpha-SMA gene knockdown experiments. In
      addition, Nutlin-3 significantly up-regulated alpha-SMA expression in primary
      endothelial cells, but not in fibroblasts and mesenchymal stem cells (MSC).
      Conversely, transforming growth factor-beta1 up-regulated alpha-SMA in
      fibroblasts and MSC, but not in macrophages and endothelial cells. Taken
      together, these data indicate that Nutlin-3 is a potent inducer of alpha-SMA in
      both normal and leukemic myeloid cells as well as in endothelial cells.

PMID- 21732355
TI  - Requirements for ion and solute transport, and pH regulation during enamel
      maturation.
AB  - Transcellular bicarbonate transport is suspected to be an important pathway used
      by ameloblasts to regulate extracellular pH and support crystal growth during
      enamel maturation. Proteins that play a role in amelogenesis include members of
      the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases
      (CAs) have also been identified. The defined functions of these genes are likely
      interlinked during enamel mineralization. The purpose of this study is to
      quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells
      obtained from secretory and maturation stages on rat incisors. We also present
      novel data on the enamel phenotypes for two animal models, a mutant porcine (CFTR
      DeltaF508) and the NBCe1-null mouse. Our data show that two SLCs (AE2 and NBCe1),
      Cftr, and Car2, Car3, Car6, and Car12 are all significantly up-regulated at the
      onset of the maturation stage of amelogenesis when compared to the secretory
      stage. The remaining SLCs and CA gene transcripts showed negligible expression or
      no significant change in expression from secretory to maturation stages. The
      enamel of CFTR-DeltaF508 adult pigs was hypomineralized and showed abnormal
      crystal growth. NBCe1-null mice enamel was structurally defective and had a
      marked decrease in mineral content relative to wild-type. These data demonstrate
      the importance of many non-matrix proteins to amelogenesis and that the
      expression levels of multiple genes regulating extracellular pH are modulated
      during enamel maturation in response to an increased need for pH buffering during
      hydroxyapatite crystal growth.

PMID- 21732356
TI  - Acetylation-dependent nuclear arrangement and recruitment of BMI1 protein to UV
      damaged chromatin.
AB  - Polycomb group (PcG) proteins, organized into Polycomb bodies, are important
      regulatory components of epigenetic processes involved in the heritable
      transcriptional repression of target genes. Here, we asked whether acetylation
      can influence the nuclear arrangement and function of the BMI1 protein, a core
      component of the Polycomb group complex, PRC1. We used time-lapse confocal
      microscopy, micro-irradiation by UV laser (355 nm) and GFP technology to study
      the dynamics and function of the BMI1 protein. We observed that BMI1 was
      recruited to UV-damaged chromatin simultaneously with decreased lysine
      acetylation, followed by the recruitment of heterochromatin protein HP1beta to
      micro-irradiated regions. Pronounced recruitment of BMI1 was rapid, with half
      time tau = 15 sec; thus, BMI1 is likely involved in the initiation step leading
      to the recognition of UV-damaged sites. Histone hyperacetylation, stimulated by
      HDAC inhibitor TSA, suppression of transcription by actinomycin D, and ATP
      depletion prevented increased accumulation of BMI1 to gammaH2AX-positive
      irradiated chromatin. Moreover, BMI1 had slight ability to recognize
      spontaneously occurring DNA breaks caused by other pathophysiological processes.
      Taken together, our data indicate that the dynamics of recognition of UV-damaged
      chromatin, and the nuclear arrangement of BMI1 protein can be influenced by
      acetylation and occur as an early event prior to the recruitment of HPbeta to UV
      irradiated chromatin.

PMID- 21732357
TI  - Inhibitory regulation of osteoclast differentiation by interleukin-3 via
      regulation of c-Fos and Id protein expression.
AB  - Interleukin-3 (IL-3) is produced under various pathological conditions and is
      thought to be involved in the pathogenesis of inflammatory diseases; however, its
      function in bone homeostasis under normal conditions or nature of the downstream
      molecular targets remains unknown. Here we examined the effect of IL-3 on
      osteoclast differentiation from mouse and human bone marrow-derived macrophages
      (BMMs). Although IL-3 can induce osteoclast differentiation of multiple myeloma
      bone marrow cells, IL-3 greatly inhibited osteoclast differentiation of human
      BMMs isolated from healthy donors. These inhibitory effects of IL-3 were only
      observed at early time points (days 0 and 1). IL-3 inhibited the expression of c
      Fos and NFATc1 in BMMs treated with RANKL. However, IL-3-mediated inhibition of
      osteoclast differentiation was not completely reversed by ectopic expression of c
      Fos or NFATc1. Importantly, IL-3 induced inhibitor of DNA binding/differentiation
      (Id)1 in hBMMs, while Id2 were sustained during osteoclast differentiation of
      mBMMs treated with IL-3. Ectopic expression of NFATc1 in Id2-deficient BMMs
      completely reversed the inhibitory effect of IL-3 on osteoclast differentiation.
      Furthermore, inflammation-induced bone erosion was markedly inhibited by IL-3
      administration. Taken together, our results suggest that IL-3 plays an inhibitory
      role in osteoclast differentiation by regulating c-Fos and Ids, and also exerts
      anti-bone erosion effects.

PMID- 21732358
TI  - Immortalization and characterization of osteoblast cell lines generated from wild
      type and Nmp4-null mouse bone marrow stromal cells using murine telomerase
      reverse transcriptase (mTERT).
AB  - Intermittent parathyroid hormone (PTH) adds new bone to the osteoporotic
      skeleton; the transcription factor Nmp4/CIZ represses PTH-induced bone formation
      in mice and as a consequence is a potential drug target for improving hormone
      clinical efficacy. To explore the impact of Nmp4/CIZ on osteoblast phenotype, we
      immortalized bone marrow stromal cells from wildtype (WT) and Nmp4-knockout (KO)
      mice using murine telomerase reverse transcriptase. Clonal lines were initially
      chosen based on their positive staining for alkaline phosphatase and capacity for
      mineralization. Disabling Nmp4/CIZ had no gross impact on osteoblast phenotype
      development. WT and KO clones exhibited identical sustained growth, reduced
      population doubling times, extended maintenance of the mature osteoblast
      phenotype, and competency for differentiating toward the osteoblast and adipocyte
      lineages. Additional screening of the immortalized cells for PTH-responsiveness
      permitted further studies with single WT and KO clones. We recently demonstrated
      that PTH-induced c-fos femoral mRNA expression is enhanced in Nmp4-KO mice and in
      the present study we observed that hormone stimulated either an equivalent or
      modestly enhanced increase in c-fos mRNA expression in both primary null and KO
      clone cells depending on PTH concentration. The null primary osteoblasts and KO
      clone cells exhibited a transiently enhanced response to bone morphogenetic
      protein 2 (BMP2). The clones exhibited lower and higher expressions of the PTH
      receptor (Pthr1) and the BMP2 receptor (Bmpr1a, Alk3), respectively, as compared
      to primary cells. These immortalized cell lines will provide a valuable tool for
      disentangling the complex functional roles underlying Nmp4/CIZ regulation of bone
      anabolism.

PMID- 21732359
TI  - Afadin controls p120-catenin-ZO-1 interactions leading to endothelial barrier
      enhancement by oxidized phospholipids.
AB  - Afadin is a novel regulator of epithelial cell junctions assembly. However, its
      role in the formation of endothelial cell junctions and the regulation of
      vascular permeability remains obscure. We previously described protective effects
      of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) in
      the in vitro and in vivo models of lung endothelial barrier dysfunction and acute
      lung injury, which were mediated by Rac GTPase. This study examined a role of
      afadin in the OxPAPC-induced enhancement of interactions between adherens
      junctions and tight junctions as a novel mechanism of endothelial cell (EC)
      barrier preservation. OxPAPC induced Rap1-dependent afadin accumulation at the
      cell periphery and Rap1-dependent afadin interaction with adherens junction and
      tight junction proteins p120-catenin and ZO-1, respectively. Afadin knockdown
      using siRNA or ectopic expression of afadin mutant lacking Rap1 GTPase binding
      domain suppressed OxPAPC-induced EC barrier enhancement and abolished barrier
      protective effects of OxPAPC against thrombin-induced EC permeability. Afadin
      knockdown also abolished protective effects of OxPAPC against ventilator-induced
      lung injury in vivo. These results demonstrate for the first time a critical role
      of afadin in the regulation of vascular barrier function in vitro and in vivo via
      coordination of adherens junction-tight junction interactions.

PMID- 21732360
TI  - The pro-apoptotic effect of quercetin in cancer cell lines requires ERbeta
      dependent signals.
AB  - Quercetin has potentially beneficial effects on disease prevention, including
      cancer. An intriguing issue regarding the mechanisms of action of quercetin is
      the ability of this drug to modulate estrogen receptor (ER) activities. In a
      previous study, we demonstrated that quercetin elicited apoptosis through an
      ERalpha-dependent mechanism. However, the contribution of ERbeta in quercetin
      induced apoptosis remains elusive. Here, we report that quercetin, at
      nutritionally relevant concentrations, mimicked the 17beta-estradiol (E2)-induced
      apoptotic effect in both ERbeta1-transfected HeLa and in ERbeta1-containing DLD-1
      colon cancer cell lines by inducing the activation of p38. p38 activation is
      responsible for pro-apoptotic activation of caspase-3 and the cleavage of
      poly(ADP-ribose) polymerase. Notably, no inactivation or downregulation of the
      survival kinases (i.e., AKT and ERK1/2) or the antiapoptotic protein Bcl-2 was
      observed after quercetin stimulation. On the contrary, quercetin acted similarly
      to E2 by increasing the levels of the oncosuppressor protein PTEN and by impeding
      ERbeta-dependent cyclin D1 promoter activity, which subsequently resulted in the
      transcription of the estrogen-responsive element remaining unchanged. As a whole,
      these data indicate that quercetin mimics the E2 effects in the presence of
      ERbeta1, thus maintaining its anti-carcinogenic potential. In addition, the
      quercetin pro-apoptotic action in the presence of ERalpha may render it as a dual
      sided protective agent against E2-related cancer in the reduction of tumour
      growth in organs that express ERalpha and/or ERbeta.

PMID- 21732361
TI  - Heterogeneity in apoptotic responses of microvascular endothelial cells to
      oxidative stress.
AB  - Oxidative stress contributes to disease and can alter endothelial cell (EC)
      function. EC from different vascular beds are heterogeneous in structure and
      function, thus we assessed the apoptotic responses of EC from lung and heart to
      oxidative stress. Since protein kinase Cdelta (PKCdelta) is activated by
      oxidative stress and is an important modulator of apoptosis, experiments assessed
      the level of apoptosis in fixed lung and heart sections of PKCdelta wild-type
      (PKCdelta(+/+)) and null (PKCdelta(-/-)) mice housed under normoxia (21% O(2)) or
      hyperoxia (~95% O(2)). We noted a significantly greater number of TUNEL-positive
      cells in lungs of hyperoxic PKCdelta(+/+) mice, compared to matched hearts or
      normoxic organs. We found that 33% of apoptotic cells identified in hyperoxic
      lungs of PKCdelta(+/+) mice were EC, compared to 7% EC in hyperoxic hearts. We
      further noted that EC apoptosis was significantly reduced in lungs of PKCdelta(-/
      ) hyperoxic mice, compared to lungs of PKCdelta(+/+) hyperoxic mice. In vitro,
      both hyperoxia and H(2)O(2) promoted apoptosis in EC isolated from
      microvasculature of lung (LMVEC), but not from the heart (HMVEC). H(2)O(2)
      treatment significantly increased p38 activity in LMVEC, but not in HMVEC.
      Inhibition of p38 attenuated H(2)O(2)-induced LMVEC apoptosis. Baseline
      expression of total PKCdelta protein, as well as the caspase-mediated,
      catalytically active PKCdelta cleavage fragment, was higher in LMVEC, compared to
      HMVEC. PKCdelta inhibition significantly attenuated H(2)O(2)-induced LMVEC p38
      activation. Conversely, overexpression of wild-type PKCdelta or the catalytically
      active PKCdelta cleavage product greatly increased H(2)O(2)-induced HMVEC caspase
      and p38 activation. We propose that enhanced susceptibility of lung EC to oxidant
      induced apoptosis is due to increased PKCdelta->p38 signaling, and we describe a
      PKCdelta-centric pathway which dictates the differential response of EC from
      distinct vascular beds to oxidative stress.

PMID- 21732362
TI  - Hyal-1 but not Hyal-3 deficiency has an impact on ovarian folliculogenesis and
      female fertility by altering the follistatin/activin/Smad3 pathway and the
      apoptotic process.
AB  - Ovarian follicle development is a process regulated by various endocrine,
      paracrine and autocrine factors that act coordinately to promote follicle growth.
      However, the vast majority of follicles does not reach the pre-ovulatory stage
      but instead, undergo atresia by apoptosis. We have recently described a role for
      the somatic hyaluronidases (Hyal-1, Hyal-2, and Hyal-3) in ovarian follicular
      atresia and induction of granulosa cell apoptosis. Herein, we show that Hyal-1
      but not Hyal-3 null mice have decreased apoptotic granulosa cells after the
      induction of atresia and an increased number of retrieved oocytes after
      stimulation of ovulation. Furthermore, young Hyal-1 null mice had a significantly
      higher number of primordial follicles than age matched wild-type animals.
      Recruitment of these follicles at puberty resulted in an increased number of
      primary and healthy preantral follicles in Hyal-1 null mice. Consequently, older
      Hyal-1 deficient female mice have prolonged fertility. At the molecular level,
      immature Hyal-1 null mice have decreased mRNA expression of follistatin and
      higher levels of phospho-Smad3 protein, resulting in increased levels of phospho
      Akt in pubertal mice. Hyal-1 null ovarian follicles did not exhibit hyaluronan
      accumulation. For Hyal-3 null mice, compensation by Hyal-1 or Hyal-2 might be
      related to the lack of an ovarian phenotype. In conclusion, our results
      demonstrate that Hyal-1 plays a key role in the early phases of folliculogenesis
      by negatively regulating ovarian follicle growth and survival. Our findings add
      Hyal-1 as an ovarian regulator factor for follicle development, showing for the
      first time an interrelationship between this enzyme and the
      follistatin/activin/Smad3 pathway.

PMID- 21732363
TI  - 18beta-glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim
      pathway in human breast cancer MCF-7 cells.
AB  - Triterpenes found in plants display a multitude of biological activities,
      including anti-tumor properties. The present study investigates the effect of
      18beta-glycyrrhetinic acid (GRA) a pentacyclic triterpenoid of the beta-amyrin
      type, isolated from the root of Licorice (Glycyrrhizza glabra) on human breast
      cancer cells, MCF-7. GRA showed potent inhibitory effects on MCF-7 proliferation
      in a concentration- and time-dependent manner without affecting immortalized
      normal mammary epithelial cell line (MCF-10A). Growth inhibition of MCF-7 cells
      by GRA occurred through apoptosis, as evident from phosphatidyl serine
      externalization and DNA fragmentation. Apoptosis was primarily mediated through
      mitochondrial death cascade as evidenced by loss of mitochondrial membrane
      potential, release of cytochrome c and activation of caspase-9. GRA induced an
      increase in Bax:Bcl-2 ratio along with a significant increase in the protein
      level of the BH3 protein Bim. SiRNA-mediated knock down of Bim markedly
      attenuated GRA-mediated apoptosis. Profiling of transcriptional regulators of Bim
      revealed a role of Forkhead box O 3a transcription factor (FOXO3a) as judged by
      increased expression and nuclear translocation of FOXO3a. Silencing of FOXO3a
      resulted in marked attenuation in the expression of Bim as well as protection
      against GRA-mediated apoptosis. Furthermore, GRA-induced activation and nuclear
      localization of FOXO3a was associated with a reduced activity of Akt kinase.
      These results suggest that GRA induces apoptosis in human breast carcinoma MCF-7
      cells via caspase activation and modulation of Akt/FOXO3a pathway.

PMID- 21732364
TI  - Duplicated chromosomal fragments stabilize shortened telomeres in normal human
      IMR-90 cells before transition to senescence.
AB  - To assess why during in vitro aging of fibroblasts the maintenance of chromosomal
      stability is effective or occasionally fails, a detailed cytogenetic analysis was
      performed in normal human IMR-90 fetal lung fibroblasts. The onset of senescence
      was inferred from proliferation activity, expression pattern of cell cycle
      regulating proteins, activity of beta-galactosidase, and morphological features.
      Over the period of proliferation, a moderate increase of non-transmissible
      structural chromosomal aberrations was observed. In addition, using fluorescence
      in situ hybridization (mFISH and mBAND) techniques, we detected clonally
      expanding translocations in up to 70% of the analyzed metaphases, all involving
      one homolog of chromosome 9 as an acceptor. Notably, chromosomes are randomly
      involved as donor-chromosomes of the translocated terminal acentric fragments.
      These fragments result from duplication because the donor chromosomes are
      apparently unchanged. Interstitial telomeric signals were detectable at fusion
      sites, most likely belonging to chromosome 9. Quantitative fluorescence in situ
      hybridization (QFISH) detecting telomere sequences, followed by mFISH technique
      revealed that already in young cells the respective telomeres of one chromosome 9
      were particularly short. For the first time, we have observed dysfunctional
      telomeres of one specific chromosome in normal human cells that have been
      stabilized by duplicated terminal sequences.

PMID- 21732365
TI  - NADPH oxidase 4 mediates upregulation of type 4 phosphodiesterases in human
      endothelial cells.
AB  - The protective actions of prostacyclin (PGI(2) ) are mediated by cyclic AMP
      (cAMP) which is reduced by type 4 phosphodiesterases (PDE4) which hydrolyze cAMP.
      Superoxide (O2(-)) from NADPH oxidase (Nox) is associated with impaired PGI(2)
      bioactivity. The objective of this study, therefore, was to study the
      relationship between Nox and PDE4 expression in human umbilical vein endothelial
      cells (HUVECs). HUVECs were incubated with the thromboxane A(2) analog, U46619, 8
      isoprostane F(2alpha) (8IP), or tumor necrosing factor alpha (TNFalpha) [+/
      iloprost (a PGI(2) analog)] and the expression of PDE4A, B, C, and D and splice
      variants thereof assessed using Western blotting and qPCR and mRNA silencing of
      Nox4 and Nox5. Effects on cell replication and angiogenesis were also studied.
      U46619, 8IP, and TNFalpha increased the expression of Nox 4 and Nox 5 and all
      PDE4 isoforms as well as cell replication and tubule formation (index of
      angiogenesis), effects inhibited by mRNA silencing of Nox4 (but not Nox5) and
      iloprost and rolipram. These data demonstrate that upregulation of Nox4 leads to
      an upregulation of PDE4A, B, and D and increased hydrolysis of cAMP which in turn
      augments cell replication and angiogenesis. This mechanism may be central to
      vasculopathies associated with endothelial dysfunction since the PGI(2)-cAMP
      signaling axis plays a key role in mediating functions that include hemostasis
      and angiogenesis.

PMID- 21732366
TI  - The transient receptor potential channel TRPV6 is dynamically expressed in bone
      cells but is not crucial for bone mineralization in mice.
AB  - Bone is the major store for Ca(2+) in the body and plays an important role in
      Ca(2+) homeostasis. During bone formation and resorption Ca(2+) must be
      transported to and from bone by osteoblasts and osteoclasts, respectively.
      However, little is known about the Ca(2+) transport machinery in these bone
      cells. In this study, we examined the epithelial Ca(2+) channel TRPV6 in bone.
      TRPV6 mRNA is expressed in human and mouse osteoblast-like cells as well as in
      peripheral blood mononuclear cell-derived human osteoclasts and murine tibial
      bone marrow-derived osteoclasts. Also other transcellular Ca(2+) transport genes,
      calbindin-D(9k) and/or -D(28K), Na(+)/Ca(2+) exchanger 1, and plasma membrane
      Ca(2+) ATPase (PMCA1b) were expressed in these bone cell types.
      Immunofluorescence and confocal microscopy on human osteoblasts and osteoclasts
      and mouse osteoclasts revealed TRPV6 protein at the apical domain and PMCA1b at
      the osteoidal domain of osteoblasts, whereas in osteoclasts TRPV6 was
      predominantly found at the bone-facing site. TRPV6 was dynamically expressed in
      human osteoblasts, showing maximal expression during mineralization of the
      extracellular matrix. 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) did not change
      TRPV6 expression in both mineralizing and non-mineralizing SV-HFO cultures.
      Lentiviral transduction-mediated overexpression of TRPV6 in these cells did not
      alter mineralization. Bone microarchitecture and mineralization were unaffected
      in Trpv6(D541A/D541A) mice in which aspartate 541 in the pore region was replaced
      with alanine to render TRPV6 channels non-functional. In summary, TRPV6 and other
      proteins involved in transcellular Ca(2+) transport are dynamically expressed in
      bone cells, while TRPV6 appears not crucial for bone metabolism and matrix
      mineralization in mice.

PMID- 21732367
TI  - Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary
      epithelial cells.
AB  - Rspo2 was identified as a novel common integration site (CIS) for the mouse
      mammary tumor virus (MMTV) in viral induced mouse mammary tumors. Here we show
      that Rspo2 modulates Wnt signaling in mouse mammary epithelial cells. Co
      expression of both genes resulted in an intermediate growth phenotype on plastic
      and had minor effects on the growth-promoting properties of Wnt1 in soft agar.
      However, individual Rspo2 and Wnt1 HC11 transfectants as well as the double
      transfectant were tumorigenic in athymic nude mice, with tumors from each line
      having distinctive histological characteristics. Rspo2 and Rspo2/Wnt1 tumors
      contained many spindle cells, consistent with an epithelial-mesenchymal
      transformation (EMT) phenotype. When Rspo2 and Rspo2/Wnt1 tumor cells were
      transferred into naive mice, they exhibited greater metastatic activity than
      cells derived from Wnt1 tumors. For comparison, C57MG/Wnt1/Rspo2 co-transfectants
      exhibited invasive properties in three-dimensional (3D) Matrigel cultures that
      were not seen with cells transfected only with Wnt1 or Rspo2. Use of Dickkopf-1,
      a specific antagonist of the Wnt/beta-catenin pathway, or short hairpin RNA
      targeting beta-catenin expression demonstrated that the invasive activity was not
      mediated by beta-catenin. Our results indicate that Rspo2 and Wnt1 have mutually
      distinct effects on mammary epithelial cell growth and these effects are context
      dependent. While Rspo2 and Wnt1 act synergistically in the beta-catenin pathway,
      other mechanisms are responsible for the invasive properties of stable double
      transfectants observed in 3D Matrigel cultures.

PMID- 21732368
TI  - Functional ion channels and cell proliferation in 3T3-L1 preadipocytes.
AB  - Mouse 3T3-L1 preadipocytes are widely used for metabolic study of obesity;
      however, their cellular physiology is not fully understood. The present study
      investigates functional ion channels and their role in the regulation of cell
      proliferation using whole-cell patch voltage-clamp, RT-PCR, Western blot, and
      cell proliferation assay in undifferentiated 3T3-L1 preadipocytes. We found three
      types of ionic currents present in 3T3-L1 preadipocytes, including an inwardly
      rectifying K(+) current (I(Kir), recorded in 15% of cells) inhibited by Ba(2+), a
      Ca(2+)-activated intermediate K(+) current (IK(Ca), recorded in 44% of cells)
      inhibited by clotrimazole (or TRAM-34) as well as a chloride current (I(Cl))
      inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in 12% of
      cells, which can be activated in all cells with hypotonic (0.8 T) insult,
      implicating a volume-sensitive I(Cl) (I(Cl.vol)). RT-PCR and Western blot
      analysis revealed the expression of KCa3.1 (for IK(Ca)), Kir2.1 (for I(Kir)), and
      Clcn3 (for I(Cl.vol)). Blockade of IK(Ca) with TRAM-34 or I(Cl.vol) with DIDS
      inhibited cell proliferation in a concentration-dependent manner. Knockdown of
      KCa3.1 or Clcn3 with specific siRNAs also suppressed cell proliferation. Flow
      cytometry analysis showed that blockade or silencing of KCa3.1 or Clcn3 channels
      with corresponding blockers or siRNAs caused an accumulation of cells at the
      G0/G1 phase. These results demonstrate that three functional ion channel
      currents, I(KCa), I(Cl.vol), and I(Kir), are heterogeneously present in 3T3-L1
      preadipocytes. I(KCa) and I(Cl.vol) participate in the regulation of cell
      proliferation.

PMID- 21732369
TI  - Parathyroid hormone-related protein is a hypertrophy factor for human mesangial
      cells: Implications for diabetic nephropathy.
AB  - Hypertrophy of human mesangial cells (HMC) is among the earliest characteristics
      in patients with diabetic nephropathy (DN). Recently, we observed the
      upregulation of parathyroid hormone (PTH)-related protein (PTHrP) in experimental
      DN, associated with renal hypertrophy. Herein, we first examined whether PTHrP
      was overexpressed in human DN, and next assessed the putative role of this
      protein on high glucose (HG)-induced HMC hypertrophy. As previously found in
      mice, kidneys from diabetic patients showed an increased tubular and glomerular
      immunostaining for PTHrP. In HMC, HG medium increased PTHrP protein expression
      associated with the development of hypertrophy as assessed by cell protein
      content. This effect was also induced by PTHrP(1-36). HG and PTHrP(1-36)-induced
      hypertrophy were associated with an increase in cyclin D1 and p27Kip1 protein
      expression, a decreased cyclin E expression, and the prevention of cyclin E/cdk2
      complex activation. Both PTHrP neutralizing antiserum (alpha-PTHrP) and the
      PTH/PTHrP receptor antagonist (JB4250) were able to abolish HG induction of
      hypertrophy, the aforementioned changes in cell cycle proteins, and also TGF
      beta1 up-regulation. Moreover, the capability of both HG and PTHrP(1-36) to
      induce HMC hypertrophy was abolished by alpha-TGFbeta1. These data show for the
      first time that PTHrP is upregulated in the kidney of patients with DN. Our
      findings also demonstrate that PTHrP acts as an important mediator of HG-induced
      HMC hypertrophy by modulating cell cycle regulatory proteins and TGF-beta1.

PMID- 21732370
TI  - Applications of circular dichroism (CD) for structural analysis of proteins:
      qualification of near- and far-UV CD for protein higher order structural
      analysis.
AB  - Circular dichroism (CD) spectroscopy is routinely used in the biopharmaceutical
      industry to study the effects of manufacturing, formulation, and storage
      conditions on protein conformation and stability, and these results are often
      included in regulatory filings. In this context, the purpose of CD spectroscopy
      is often to verify that a change in the formulation or manufacturing process of a
      product has not produced a change in the conformation of a protein. A comparison
      of two or more spectra is often required to confirm that the protein's structure
      has been maintained. Traditionally, such comparisons have been qualitative in
      nature, based on visually inspecting the overlaid spectra. However, visual
      assessment is inherently subjective and therefore prone to error. Furthermore,
      recent requests from regulatory agencies to demonstrate the suitability of the CD
      spectroscopic method for the purpose of comparing spectra have highlighted the
      need to appropriately qualify CD spectroscopy for characterization of
      biopharmaceutical protein products. In this study, we use a numerical spectral
      comparison approach to establish the precision of the CD spectroscopic method and
      to demonstrate that it is suitable for protein structural characterization in
      numerous biopharmaceutical applications.

PMID- 21732371
TI  - Moisture content impacts the stability of DNA adsorbed onto gold microparticles.
AB  - Particle-mediated epidermal delivery (PMED) of small quantities of DNA (0.5-4.0
      MUg) has been reported to both induce an immune response and protect against
      disease in human subjects. In order for the PMED of DNA to be a viable technique
      for vaccination, the adsorbed DNA must be stable during shipping and storage.
      Here, we report that the storage stability of plasmid DNA adsorbed to 2-MUm gold
      particles is strongly dependent on sample water content. Gold/DNA samples stored
      at 60 degrees C and 6% relative humidity (RH) maintained supercoil content after
      4-month storage, whereas storage at higher RHs facilitated degradation. Storage
      with desiccants had stabilizing effects on DNA similar to storage at 6% RH.
      However, storage with "indicating" Drierite and phosphorus pentoxide resulted in
      enhanced rates of DNA degradation.

PMID- 21732372
TI  - Designed experiments with binary responses.

PMID- 21732373
TI  - Introduction: the human sciences and Cold War America.
AB  - Studies of the history of the human sciences during the Cold War era have
      proliferated over the past decade--in JHBS and elsewhere. This special issue
      focuses on the connections between the behavioral sciences and the culture and
      politics of the Cold War in the United States. In the recent literature, there is
      a tendency to identify the Cold War human sciences with two main paradigms: that
      of psychocultural analysis, on the one hand, and of the systems sciences, on the
      other. The essays in the special issue both extend understanding of each of these
      interpretive frameworks and help us to grasp their interconnection.

PMID- 21732374
TI  - The last stand of the psychocultural cold warriors: military contract research in
      Vietnam.
AB  - In 1966, the social scientists of the Simulmatics Corporation arrived in Saigon.
      Tasked by the Pentagon with helping to pacify South Vietnam, they conducted
      political and social psychological research on Viet Cong defectors, government
      soldiers, and Vietnamese villagers. This essay argues that Simulmatics's work
      captures some of the ironies of Cold War social science: its tendency to mask
      militarization behind the rhetoric of peaceful nation-building, its blurring of
      data collection and intelligence gathering, and its ambitious dedication to
      revealing the unseen contents of hearts and minds while remaining ignorant of the
      historical, cultural, and linguistic contexts in which its subjects lived.

PMID- 21732375
TI  - X-rays of inner worlds: the mid-twentieth-century American projective test
      movement.
AB  - This essay begins to tell the neglected history of the projective test movement
      in the U.S. behavioral sciences from approximately 1941 to 1968. This cross
      disciplinary enterprise attempted to use projective techniques as "X-ray"
      machines to see into the psyches of subjects tested around the world. The aim was
      to gather subjective materials en masse, pursuing data on a scope, scale, and
      manner rarely hazarded before in any science. In particular, the targeted data
      included the traces of the inner life and elusive aspects of subjective
      experience including dreams, life stories, and myriad test results from a battery
      of tests. This essay explores how the movement and the experimental data bank
      that resulted were unlikely yet telling sites for the practice and pursuit of the
      Cold War human sciences. To look closely at the encounters that resulted is to
      show how the most out-of-the-way places and seemingly insignificant moments
      played a role in heady scientific ambitions and global geopolitical projects. At
      times, the projective test movement became a mirror of Cold War rationality
      itself, as tests were employed at the very limits of their possible extension.
      The essay argues for an off-kilter centrality in the movement itself, shedding
      light on the would-be unified social sciences after World War II and the
      "subjective turn" they took.

PMID- 21732376
TI  - Cyborg pantocrator: international relations theory from decisionism to rational
      choice.
AB  - International relations theory took shape in the 1950s in reaction to the
      behavioral social science movement, emphasizing the limits of rationality in a
      context of high uncertainty, weak rules, and the possibility of lethal conflict.
      Yet the same discipline rapidly developed "rational choice" models applied to
      foreign policy decision making or nuclear strategy. This paper argues that this
      transformation took place almost seamlessly around the concept of "decision."
      Initially associated with an antirationalist or "decisionist" approach to
      politics, the sovereign decision became the epitome of political rationality when
      it was redescribed as "rational choice," thus easing the cultural acceptance of
      political realism in the postwar years.

PMID- 21732377
TI  - Chicago neoliberalism versus Cowles planning: perspectives on patents and public
      goods in Cold War economic thought.
AB  - In post-Sputnik America, when many policymakers and social scientists feared the
      Soviet Union had a technological advantage over the United States, assessing the
      relative importance of patents for inventive activity and examining whether
      scientific research constituted a public good were paramount concerns. The
      neoliberals of the University of Chicago and the planners of the Cowles
      Commission both spoke to these issues. This paper sheds light on their views on
      patents and public goods in the late 1950s and early 1960s by examining
      representatives of Cowles and Chicago, Kenneth Arrow and Ronald Coase,
      respectively. Furthermore, it evaluates whether their views on patents and public
      goods clashed with the interests of RAND, at which both Arrow and Coase worked at
      some point during this time period. The paper argues that the Chicago-neoliberal
      position of Coase undermined the interests of RAND, while the Cowles-planning
      conclusions of Arrow furthered those interests.

PMID- 21732381
TI  - Assessment of the effect of the non-volatile wine matrix on the volatility of
      typical wine aroma compounds by headspace solid phase microextraction/gas
      chromatography analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of the whole non
      volatile wine matrix composition on the volatility of typical wine aroma
      compounds by comparing the slopes of regression lines of five deodorised and
      reconstituted wines with the slopes calculated for the same compounds in a
      control wine with no matrix effect. RESULTS: The main effect observed was a
      reduction in the slopes, or a retention effect, that was largest for the
      reconstituted sparkling wine, which showed between 11 and 69% lower slopes than
      the control wine. In addition, an increase in the slopes, or a 'salting-out'
      effect, in the most compositionally complex reconstituted aged-red and sweet
      wines was also noticed for some volatiles with a very low boiling point or a low
      hydrophobic constant value. CONCLUSION: This study has shown that the non
      volatile composition of wines strongly affects the volatility of wine aroma
      compounds. In addition, the aroma chemical class, in particular its
      physicochemical properties (volatility and hydrophobicity), strongly influences
      this behaviour. On the basis of these results, many odour threshold values
      calculated in simple hydroalcoholic solutions and usually employed to evaluate
      the odour importance of specific volatile compounds may have been over- or
      underestimated.

PMID- 21732382
TI  - Effect of phenolic acids on the rheological properties and proteins of hard wheat
      flour dough and bread.
AB  - BACKGROUND: The effects of different phenolic acids on the rheological properties
      and gluten proteins of hard wheat flour dough and bread were investigated.
      Caffeic, ferulic, syringic and gallic acids were each blended with hard wheat
      flour at a concentration of 4.44 umol L(-1) g(-1) flour. RESULTS: Mixing time and
      tolerance were reduced with the addition of phenolic acids. The phenolic acids
      reduced the maximum resistance to extension (R(max)) and increased the
      extensibility of dough, with effects in the following order: gallic < syringic <
      ferulic < caffeic acid. The effect on R(max) was more pronounced in overmixed
      dough. Loaf volume was most significantly decreased with the addition of caffeic
      acid. Extraction of sodium dodecyl sulfate-soluble high-molecular-weight proteins
      was increased in both mixed and fermented doughs by the addition of ferulic and
      caffeic acids. The order of influence of the phenolic acids on the rheological
      properties and protein structure of dough and bread was consistent with that of
      their antioxidant activity. CONCLUSION: The addition of caffeic and ferulic acids
      reduced R(max) and increased the extensibility of hard wheat flour dough by
      modifying the high-molecular-weight gluten, which resulted in decreased bread
      volume.

PMID- 21732383
TI  - Optimization of peptic hydrolysis parameters for the production of angiotensin I
      converting enzyme inhibitory hydrolysate from Acetes chinensis through Plackett
      Burman and response surface methodological approaches.
AB  - BACKGROUND: Angiotensin I-converting enzyme (ACE) plays an important
      physiological role in regulating blood pressure. The elevation of blood pressure
      could be suppressed by inhibiting ACE. ACE inhibitory peptides derived from food
      proteins could exert antihypertensive effects without side effects. Acetes
      chinensis is a marine shrimp suitable for the production of ACE inhibitory
      peptides. The principal objective of this study was to screen for the significant
      variables, and further to optimize the levels of the selected variables, for the
      enzymatic production of ACE inhibitory peptides from Acetes chinensis. RESULTS:
      Plackett-Burman design and response surface methodology were employed to optimize
      the peptic hydrolysis parameters of Acetes chinensis to obtain a hydrolysate with
      potent ACE inhibitory activity. The peptic hydrolysis variables were subject to a
      Plackett-Burman design for screening the main factors. The selected significant
      parameters such as pH, hydrolysis temperature and enzyme/substrate (E/S) ratio
      were further optimized using a central composite design. The optimized conditions
      were: pH 2.5, hydrolysis temperature 45  degrees C, E/S ratio 17 800 U kg(-1)
      shrimp and substrate concentration 200 g L(-1). The results showed that 3-5 h
      hydrolysis could result in a hydrolysate with ACE inhibition IC(50) of 1.17 mg
      mL(-1) and a high DH of 25-27%. CONCLUSION: Plackett-Burman design and RSM
      performed well in the optimization of peptic hydrolysis parameters of Acetes
      chinensis to produce hydrolysate with ACE inhibitory activity. A hydrolysate with
      potent ACE inhibitory activity and high degree of hydrolysis was obtained, so
      that the yield of ACE inhibitory peptides in it was high.

PMID- 21732384
TI  - Comparison of cell wall metabolism in the pulp of three cultivars of 'Nanfeng'
      tangerine differing in mastication trait.
AB  - BACKGROUND: Like sweet orange (Citrus sinensis), tangerine (Citrus reticulata) is
      another citrus crop grown widely throughout the world. However, whether it shares
      a common mechanism with sweet orange in forming a given mastication trait is
      still unclear. In this study, three 'Nanfeng' tangerine cultivars, 'Yangxiao-26'
      ('YX-26') with inferior mastication trait, elite 'YX-26' with moderate
      mastication trait and 'Miguang' ('MG') with superior mastication trait, were
      selected to investigate the formation mechanism of mastication trait. RESULTS:
      'MG' had the lowest contents of total pectin, protopectin and lignin and the
      highest gene expression levels of citrus polygalacturonase (PG) and pectin
      methylesterase (PME) at the end of fruit ripening, whereas 'YX-26' had the lowest
      water-soluble pectin (WSP) content, the highest lignin content and the lowest PG
      and PME expression levels. The contents of cellulose and hemicellulose were
      similar among the three tangerines. CONCLUSION: The fruit mastication trait of C.
      reticulata was determined by the proportions of WSP and protopectin as well as
      lignin content, not by cellulose and hemicellulose contents. Pectin content could
      be a major contribution to the feeling of mastication trait, while PG and PME
      exhibited an important role in forming a given mastication trait according to the
      present results as well as previous results for C. sinensis.

PMID- 21732385
TI  - Effects of ethylene, cytokinin and physical treatments on BoPaO gene expression
      of harvested broccoli.
AB  - BACKGROUND: Broccoli is a highly perishable vegetable that shows enhanced
      postharvest senescence and intense de-greening caused by chlorophyll degradation.
      One of the key steps of chlorophyll catabolism is the opening of chlorophyll
      tretrapyrrole catalysed by pheophorbide a oxygenase (PaO). In this study the
      expression of a gene encoding a putative PaO was characterised under several
      chemical and physical treatments. RESULTS: A fragment of a gene encoding a PaO
      from broccoli (BoPaO) was cloned. The expression of BoPaO showed an important
      increment during postharvest senescence, in correlation with chlorophyll
      degradation. Furthermore, broccoli heads were treated with the hormones cytokinin
      and ethylene. Cytokinin delayed the increment in BoPaO expression, while ethylene
      accelerated the process. Also, several postharvest treatments were applied in
      order to evaluate their effect on BoPaO expression. Samples treated with modified
      atmosphere, hot air, UV-C or white light showed a delay in chlorophyll
      degradation and de-greening. In most cases the treatments also delayed the
      increment in BoPaO expression during senescence. CONCLUSION: A close correlation
      between chlorophyll degradation and BoPaO expression was found during broccoli
      senescence. This relationship was corroborated in samples treated with different
      hormonal and physical applications.

PMID- 21732386
TI  - Transoral approach for Stensen's duct lithiasis.
AB  - INTRODUCTION: Extracorporeal lithotripsy (ECL) and interventional sialendoscopy
      are the classical treatments for Stensen's duct salivary stones, but some cases
      cannot be treated using these techniques. Another technique is now available,
      transoral Stensen's duct approach. TECHNICAL NOTE: Transoral Stensen's duct
      approach can be performed under local anesthesia. The exact location of Stensen's
      duct is confirmed after introduction of a 0000 probe (Storz((r)) ) in the duct
      that is stopped by the impacted stone. This may be confirmed on preoperative
      noninjected CT-scan. During this approach, the surgeon passes the mucosa and
      buccinator muscle, tracts the buccal fat pad laterally, and then finds the duct.
      During this procedure one must avoid harming the superior buccal branch of the
      facial nerve by dissecting gently close to the duct. When the duct is found, the
      stone is easily removed with a ductal lateral incision or better 12 o'clock
      ductal incision. DISCUSSION: Transoral approach of Stensen's duct salivary
      lithiasis is an easy, fast, and inexpensive technique that can be recommended in
      case sialendoscopy surgery fails. Morbidity for patients is much lower than that
      of classical parotidectomy.

PMID- 21732387
TI  - Cognitive and emotional covariates of violence exposure among former prisoners:
      links to antisocial behavior and emotional distress and implications for theory.
AB  - In this study, formerly incarcerated men (N = 123) were assessed for their
      experiences with violence in the community as well as their current behavioral
      and mental health status (antisocial behavior and emotional distress).
      Participants also completed measures of two constructs theorized to moderate
      relations between exposure to violence and outcomes: cognitive beliefs supporting
      aggressive responding and negative emotional reactivity to witnessed violence.
      Data on key social-demographic background factors affecting outcomes were also
      collected. Analyses showed that, after controlling the effects of background
      factors, relationships between experiences with violence in the community and
      behavioral/mental health were moderated by cognitive beliefs and emotional
      reactivity. At high levels of support for aggressive responding, significant
      positive links were observed between exposure to violence and antisocial behavior
      as well as emotional distress. At high levels of negative reactivity to violence,
      a significant positive link was observed between exposure to violence and
      emotional distress (but not antisocial behavior). Findings are discussed with
      respect to research and theory on the effects of exposure to violence in high
      risk adult populations.

PMID- 21732388
TI  - Scanning electron microscopy of Streptomyces without use of any chemical
      fixatives.
AB  - A new, short, and quick method was developed for preparation of specimen for
      observing Actinomycetes of genus Streptomyces by scanning electron microscopy.
      The cultures were directly grown on stubs and coated with a film of gold without
      using any fixative and dehydrating procedures. Using this simple preparation
      procedure, surface of intact sporing structures of Streptomyces was observed over
      a range of magnifications. As the preparation procedure is so simple and rapid,
      this procedure could be most useful for the routine examination and
      identification of Streptomyces.

PMID- 21732389
TI  - Two-level hierarchical parallelization of second-order Moller-Plesset
      perturbation calculations in divide-and-conquer method.
AB  - A two-level hierarchical parallelization scheme including the second-order Moller
      Plesset perturbation (MP2) theory in the divide-and-conquer method is presented.
      The scheme is a combination of coarse-grain parallelization assigning each
      subsystem to a group of processors, with fine-grain parallelization, where the
      computational tasks for evaluating MP2 correlation energy of the assigned
      subsystem are distributed among processors in the group. Test calculations
      demonstrate that the present scheme shows high parallel efficiency and makes MP2
      calculations practical for very large molecules.

PMID- 21732390
TI  - Optimal scaling factors for CM1 and CM3 atomic charges in RM1-based aqueous
      simulations.
AB  - Scaling factors for atomic charges derived from the RM1 semiempirical quantum
      mechanical wavefunction in conjunction with CM1 and CM3 charge models have been
      optimized by minimizing errors in absolute free energies of hydration,
      DeltaG(hyd) , for a set of 40 molecules. Monte Carlo statistical mechanics
      simulations and free energy perturbation theory were used to annihilate the
      solutes in gas and in a box of TIP4P water molecules. Lennard-Jones parameters
      from the optimized potentials for liquid simulations-all atom (OPLS-AA) force
      field were utilized for the organic compounds. Optimal charge scaling factors
      have been determined as 1.11 and 1.14 for the CM1R and CM3R methods,
      respectively, and the corresponding unsigned average errors in DeltaG(hyd)
      relative to experiment were 2.05 and 1.89 kcal/mol. Computed errors in aniline
      and two derivatives were particularly large for RM1 and their removal from the
      data set lowered the overall errors to 1.61 and 1.75 kcal/mol for CM1R and CM3R.
      Comparisons are made to the AM1 method which yielded total errors in DeltaG(hyd)
      of 1.50 and 1.64 kcal/mol for CM1A*1.14 and CM3A*1.15, respectively. This work is
      motivated by the need for a highly efficient yet accurate quantum mechanical (QM)
      method to study condensed-phase and enzymatic chemical reactions via mixed QM and
      molecular mechanical (QM/MM) simulations. As an initial test, the Menshutkin
      reaction between NH(3) and CH(3) Cl in water was computed using a RM1/TIP4P
      Ew/CM3R procedure and the resultant DeltaG(?) , DeltaG(rxn) , and geometries were
      in reasonable accord with other computational methods; however, some potentially
      serious shortcomings in RM1 are discussed.

PMID- 21732391
TI  - Computational protocols for prediction of solute NMR relative chemical shifts. a
      case study of L-tryptophan in aqueous solution.
AB  - In this study, we have applied two different spanning protocols for obtaining the
      molecular conformations of L-tryptophan in aqueous solution, namely a molecular
      dynamics simulation and a molecular mechanics conformational search with
      subsequent geometry re-optimization of the stable conformers using a quantum
      mechanically based method. These spanning protocols represent standard ways of
      obtaining a set of conformations on which NMR calculations may be performed. The
      results stemming from the solute-solvent configurations extracted from the MD
      simulation at 300 K are found to be inferior to the results stemming from the
      conformations extracted from the MM conformational search in terms of replicating
      an experimental reference as well as in achieving the correct sequence of the NMR
      relative chemical shifts of L-tryptophan in aqueous solution. We find this to be
      due to missing conformations visited during the molecular dynamics run as well as
      inaccuracies in geometrical parameters generated from the classical molecular
      dynamics simulations.

PMID- 21732392
TI  - A comparison of neighbor search algorithms for large rigid molecules.
AB  - Fast determination of neighboring atoms is an essential step in molecular
      dynamics simulations or Monte Carlo computations, and there exists a variety of
      algorithms to efficiently compute neighbor lists. However, most of these
      algorithms are general, and not specifically designed for a given type of
      application. As a result, although their average performance is satisfactory,
      they might be inappropriate in some specific application domains. In this
      article, we study the case of detecting neighbors between large rigid molecules,
      which has applications in, e.g., rigid body molecular docking, Monte Carlo
      simulations of molecular self-assembly or diffusion, and rigid body molecular
      dynamics simulations. More precisely, we compare the traditional grid-based
      algorithm to a series of hierarchy-based algorithms that use bounding volumes to
      rapidly eliminate large groups of irrelevant pairs of atoms during the neighbor
      search. We compare the performance of these algorithms based on several
      parameters: the size of the molecules, the average distance between them, the
      cutoff distance, as well as the type of bounding volume used in the culling
      hierarchy (AABB, OBB, wrapped, or layered spheres). We demonstrate that for
      relatively large systems (> 100,000 atoms) the algorithm based on the hierarchy
      of wrapped spheres shows the best results and the traditional grid-based
      algorithm gives the worst timings. For small systems, however, the grid-based
      algorithm and the one based on the wrapped sphere hierarchy are beneficial.

PMID- 21732393
TI  - Low prevalence of genetic prenatal diagnosis in Japan.

PMID- 21732394
TI  - Genome-wide array-based copy number profiling in human placentas from unexplained
      stillbirths.
AB  - OBJECTIVE: Accumulating evidence suggests that genomic structural variations,
      particularly copy number variations (CNV), are a common occurrence in humans that
      may bear phenotypic consequences for living individuals possessing the variant.
      While precise estimates vary, large-scale karyotypic abnormalities are present in
      6-12% of stillbirths (SB). However, due to inherent limitations of conventional
      cytogenetics, the contribution of genomic aberrations to stillbirth is likely
      underrepresented. High-resolution copy number variant analysis by genomic array
      based profiling may overcome such limitations. METHODS: Prospectively acquired SB
      cases > 22 weeks underwent classification of 'unexplained' stillbirth by
      Wigglesworth and Aberdeen criteria after extensive testing and rigorous
      multidisciplinary audit. Genome-wide analysis was conducted using high-resolution
      Illumina single nucleotide polymorphism (SNP) arrays (Human CNV370-Duo) on
      placental and fetal samples. Potential alternate detection methods were completed
      by one or more of three independent means (quantitative PCR, Illumina1M, or
      Agilent105K comparative genomic hybridization arrays). RESULTS: In our cohort of
      54 stillbirths, 29 met strict unexplained criteria. Among these, we identified 24
      putative novel CNVs. Subsequent interrogation detected 18 of 24 CNVs (75%) in
      placental samples, 8 of which were also confirmed in available fetal samples;
      none were present in maternal blood. CONCLUSION: We describe the potential of
      whole-genome placental profiling to identify small genomic imbalances, which
      might contribute to a small proportion of well-characterized, unexplained
      stillbirths.

PMID- 21732396
TI  - Probiotics function mechanistically as delivery vehicles for neuroactive
      compounds: Microbial endocrinology in the design and use of probiotics.
AB  - I hypothesize here that the ability of probiotics to synthesize neuroactive
      compounds provides a unifying microbial endocrinology-based mechanism to explain
      the hitherto incompletely understood action of commensal microbiota that affect
      the host's gastrointestinal and psychological health. Once ingested, probiotics
      enter an interactive environment encompassing microbiological, immunological, and
      neurophysiological components. By utilizing a trans-disciplinary framework known
      as microbial endocrinology, mechanisms that would otherwise not be considered
      become apparent since any candidate would need to be shared among all three
      components. The range of neurochemicals produced by probiotics includes
      neurochemicals for which receptor-based targets on immune and neuronal elements
      (intestinal and extra-intestinal) have been well characterized. Production of
      neurochemicals by probiotics therefore allows for their consideration as delivery
      vehicles for neuroactive compounds. This unifying microbial endocrinology-based
      hypothesis, which may facilitate the selection and design of probiotics for
      clinical use, also highlights the largely unrecognized role of neuroscience in
      understanding how microbes may influence health.

PMID- 21732397
TI  - Neuroactive probiotics.

PMID- 21732398
TI  - Ultra high-performance liquid chromatography of porphyrins.
AB  - An ultra high-performance liquid chromatographic (UHPLC) system was developed and
      optimized for the separation of porphyrins of clinical interest. Optimum
      conditions for the simultaneous separation of uroporphyrin, hepta-, hexa-, penta
      carboxylic acid porphyrins and coproporphyrin and their type I and III isomers on
      a Thermo Hypersil BDS C18 column (2.4 um particle size, 100 * 2.1 mm i.d.) using
      a gradient elution with 10% (v/v) acetonitrile in 1.0 m ammonium acetate buffer
      (pH 5.16) and 10% (v/v) acetonitrile in methanol at a flow-rate of 0.4 mL/min.
      The effect of mobile phase buffer molarity on the sensitivity of fluorescence
      detection and resolution of porphyrin isomers was investigated. The method was
      successfully applied to the analysis of porphyrins extracted from the urine and
      faeces of patients with various human porphyrias.

PMID- 21732399
TI  - Social factors influencing natal dispersal in male white-faced capuchins (Cebus
      capucinus).
AB  - White-faced capuchin males disperse from their natal group at around 4.5 years of
      age, but there is much variation in dispersal timing: our youngest confirmed
      disperser was 19 months and the oldest 11 years old. In this study, we
      investigate possible factors influencing dispersal decisions in this species.
      Between 1983 and 2010, 64 males were born into three study groups in Santa Rosa
      National Park, Area de Conservacion Guanacaste, and Costa Rica. As of August
      2010, 21 died or were presumed dead (<14 months), 13 remained natal residents,
      and 30 were presumed dispersers. We used backward logistic regression to identify
      proximate factors that predict the occurrence of male natal dispersal. The
      occurrence of a takeover (significant positive association) and group size
      (nonsignificant negative association) were included in the model. Male age,
      number of maternal brothers, and number of adult males were not significant
      predictors of natal dispersal. The resultant model correctly classified 97% of
      dispersed and 89% of resident natal males, for an overall success rate of 95%.
      The occurrence of a group takeover was the strongest predictor of male dispersal,
      with natal males being 18.7 times more likely to disperse in the context of a
      group takeover than during peaceful times. A linear regression model showed that
      the tenure length of a male's probable father influences the age of natal
      dispersal, explaining 15% of the observed variation in age. However, when our
      oldest disperser was removed (an outlier) this effect disappeared. Collectively,
      these results indicate that group instability, as evidenced by the occurrence of
      a takeover, shorter tenure length of a natal male's father, and smaller group
      size, triggers natal dispersal in this species while the converse leads to a
      delay. These data add to our growing evidence of the enormous impact that
      takeovers have on the behavioral ecology of this species.

PMID- 21732400
TI  - Langerhans cell histiocytosis with central nervous system involvement--complete
      response to 2-chlorodeoxyadenosine after failure of tyrosine kinase inhibitor
      therapies with sorafenib and imatinib.
AB  - Langerhans cell histiocytosis (LCH) is rare in adults, and only a subset of these
      patients suffers from central nervous system (CNS) involvement. Hence, evidence
      based treatment recommendations are lacking. A case of a 20-year-old student with
      multisystem LCH and extensive CNS involvement is described, who showed a durable
      response to 2-chlorodeoxyadenosine after prior therapies with the tyrosine kinase
      inhibitors sorafenib and imatinib. In accordance to the experiences provided by
      other case series, which are reviewed herein, 2-chlorodeoxyadenosine can be
      considered an effective and safe option for adult LCH with CNS involvement.

PMID- 21732402
TI  - Prenatal immune challenge compromises the normal course of neurogenesis during
      development of the mouse cerebral cortex.
AB  - Maternal infection during pregnancy is an environmental risk factor for the
      development of severe brain disorders in offspring, including schizophrenia and
      autism. However, little is known about the neurodevelopmental mechanisms
      underlying the association between prenatal exposure to infection and the
      emergence of cognitive and behavioral dysfunctions in later life. By injecting
      viral mimetic polyriboinosinic-polyribocytidylic acid (Poly I:C) into mice, we
      investigated the influence of maternal immune challenge during pregnancy on the
      development of the cerebral cortex of offspring. Our previous study showed that
      stimulation of the maternal immune system compromised the expression properties
      of transcription factors and the synaptogenesis of cortical neurons in upper
      layers but not those in deeper layers. The objective of the current study was to
      examine further whether maternal immune challenge has an influence on the
      cellular-biological features of the cortical progenitors that generate distinct
      cortical neuronal subtypes. We found the following abnormalities in the cortex of
      mice given the prenatal Poly I:C injection during later stages of cortical
      neurogenesis. First, proliferative activity and the expression of Pax6, which is
      a master regulator of the gene expression of transcription factors, were
      significantly decreased in the cortical progenitors. Second, the laminar
      allocation and gene expression were significantly altered in the daughter neurons
      generated at the same birth dates. These results demonstrate that specific
      abnormalities in the cortical progenitors preceded deficits in neuronal
      phenotypes. These changes may underlie the emergence of psychiatric brain and
      behavioral dysfunctions after in utero exposure to an infection.

PMID- 21732401
TI  - Noninvasive measurement of brain glycogen by nuclear magnetic resonance
      spectroscopy and its application to the study of brain metabolism.
AB  - Glycogen is the reservoir for glucose in the brain. Beyond the general agreement
      that glycogen serves as an energy source in the central nervous system, its exact
      role in brain energy metabolism has yet to be elucidated. Experiments performed
      in cell and tissue culture and animals have shown that glycogen content is
      affected by several factors, including glucose, insulin, neurotransmitters, and
      neuronal activation. The study of in vivo glycogen metabolism has been hindered
      by the inability to measure glycogen noninvasively, but, in the past several
      years, the development of a noninvasive localized (13) C nuclear magnetic
      resonance (NMR) spectroscopy method has allowed the study of glycogen metabolism
      in the conscious human. With this technique, (13) C-glucose is administered
      intravenously, and its incorporation into and washout from brain glycogen is
      tracked. One application of this method has been to the study of brain glycogen
      metabolism in humans during hypoglycemia: data have shown that mobilization of
      brain glycogen is augmented during hypoglycemia, and, after a single episode of
      hypoglycemia, glycogen synthesis rate is increased, suggesting that glycogen
      stores rebound to levels greater than baseline. Such studies suggest that
      glycogen may serve as a potential energy reservoir in hypoglycemia and may
      participate in the brain's adaptation to recurrent hypoglycemia and eventual
      development of hypoglycemia unawareness. Beyond this focused area of study, (13)
      C NMR spectroscopy has a broad potential for application in the study of brain
      glycogen metabolism and carries the promise of a better understanding of the role
      of brain glycogen in diabetes and other conditions.

PMID- 21732403
TI  - Clozapine and lithium require Caenorhabditis elegans beta-arrestin and serum- and
      glucocorticoid-inducible kinase to affect Daf-16 (FOXO) localization.
AB  - Numerous studies have implicated low levels of signaling in the Akt network with
      psychotic illnesses, and a growing body of literature has shown that all classes
      of antipsychotic drugs increase Akt signaling. The most clinically effective
      antipsychotic drug is clozapine. With Caenorhabditis elegans as a model system,
      this study demonstrates that clozapine is unique among antipsychotic drugs
      because it requires beta-arrestin and serum and glucocorticoid-inducible kinase
      (SGK) in addition to Akt to suppress the nuclear localization of DAF-16 (Forkhead
      box O [FOXO]). Lithium, a mood stabilizer often used to treat psychosis, also
      requires beta-arrestin and SGK to suppress the nuclear localization of DAF-16.

PMID- 21732404
TI  - Female reproductive tract of the lesser anteater (Tamandua tetradactyla,
      myrmecophagidae, Xenarthra). Anatomy and histology.
AB  - The morphological and histological features of the unusual reproductive tract of
      the female lesser anteater, Tamandua tetradactyla (Myrmecophagidae, Xenarthra),
      are described for the first time. The present study aimed to establish the main
      similarities and differences between this species and other xenarthrans. The
      populations of this species are declining rapidly for a number of reasons and our
      study is relevant to diverse programs related to its conservation. Studies were
      carried out on five female genital tracts of adult specimens. Ovaries were ovoid,
      presenting a medulla completely surrounded by the cortex, differently from that
      described in other xenarthans. Like in Dasypus but different from all other
      armadillos studied, single oocyte follicles were observed and a simple the
      uterus. The uterovaginal canal connects the uterus with the urogenital sinus. The
      simple columnar epithelium of the uterovaginal canal ends abruptly at a septum
      which resembles a hymen, where the transitional epithelium of the urogenital
      sinus appears. This ancestral feature is shared with that of other armadillos,
      except Tolypeutes matacus, which has a true vagina. Characteristics of the
      reproductive tract and sperm morphology of other Xenarthra are comparatively
      discussed. These observations suggest that important reproductive features are
      shared between the family Myrmecophagidae and the genus Dasypus, a basal group in
      the phylogeny of Xenarthra.

PMID- 21732405
TI  - An in vitro correlation of metastatic capacity, substrate rigidity, and ECM
      composition.
AB  - The process of metastasis requires a metastatic cancer cell to invade a variety
      of micro-environments of variable stiffnesses. Unlike metastatic cells, normal
      cell function and viability is dependent on the stiffness of the environment and
      used as a cue to maintain cell health and proper tissue organization. In this
      study we have asked if metastatic cells can ignore the parameter of stiffness and
      if this ability is gradually acquired and if so, through what mechanism. Using a
      panel of mouse mammary tumor cells derived from the same parental tumor, but
      possessing different metastatic abilities, we cultured the cells on hard and soft
      substrates conjugated with collagen or fibronectin. Normal and non-metastatic
      tumor cells responded to changes in stiffness on fibronectin, but not collagen.
      However, the more metastatic cells ignored the change in stiffness on fibronectin
      coated substrates. This lack of response on fibronectin correlated with a change
      in the expression level of the alpha3 integrin subunit, activation of the beta1
      subunit, and phosphorylation of FAKpY397. We conclude that through fibronectin,
      changes in the activation and tethering of the beta-1 integrin provides a
      mechanism for metastatic cells to disregard changes in compliance to survive and
      navigate in environments of different stiffness.

PMID- 21732406
TI  - Curcumin protects against ovariectomy-induced bone loss and decreases
      osteoclastogenesis.
AB  - Curcumin has anti-oxidative activity. In view of the increasing evidence for a
      biochemical link between increased oxidative stress and reduced bone density we
      hypothesized that curcumin might increase bone density by elevating antioxidant
      activity in some target cell type. We measured bone density by Micro-CT, enzyme
      expression levels by quantitative PCR or enzyme activity, and osteoclast (OC)
      formation by tartrate-resistant acid phosphatase staining. The bone mineral
      density of the femurs of curcumin-administered mice was significantly higher than
      that of vehicle-treated mice after ovariectomy (OVX) and this was accompanied by
      reduced amounts of serum collagen-type I fragments, which are markers of bone
      resorption. Curcumin suppressed OC formation by increasing receptor activator of
      nuclear factor-kappaB ligand (RANKL)-induced glutathione peroxidase-1, and
      reversed the stimulatory effect of homocysteine, a known H(2) O(2) generator, on
      OC formation by restoring Gpx activity. Curcumin generated an aberrant RANKL
      signal characterized by reduced expression of nuclear factor of activated T cells
      2 (NFAT2) and attenuated activation of mitogen-activated protein kinases (ERK,
      JNK, and p38). Curcumin thus inhibited OVX-induced bone loss, at least in part by
      reducing osteoclastogenesis as a result of increased antioxidant activity and
      impaired RANKL signaling. These findings suggest that bone loss associated with
      estrogen deficiency could be attenuated by curcumin administration.

PMID- 21732407
TI  - PI3K/Akt responses to oxytocin stimulation in Caco2BB gut cells.
AB  - Recently, we discovered oxytocin receptor (OTR) expression in the developing gut
      villus epithelium that emerges in villus-crypt junctions after weaning. Oxytocin
      (OT) and OTR regulate many physiological functions in various tissues; however,
      their function in gut epithelium is unknown. We explored responses of PI3K and
      Akt phosphoisoforms to OT stimuli in the Caco2BB human gut cell line. In Caco2BB
      cells, PI3K and pAkt levels peaked at 62.5  nM OT. At higher concentrations, PI3K
      decreased more gradually than pAkt(S473) suggesting that the pAkt(S473) response
      is separate from PI3K. At <=7.8  nM OT, pAkt(T308) increased while pAkt(S473)
      decreased. Using a specific OTR antagonist, we demonstrated that responses of
      pAkt(T308) to OT depend on OTR in contrast to the partial OTR-dependence of the
      pAkt(S473) response. Differential pAkt phosphoisoform responses included pAkt
      phosphoserine 473 persistently free of phosphothreonine 308. The reduction in
      PI3K after 62.5  nM OT for 30  min coincided with OTR internalization. The
      PI3K/Akt activation profile was somewhat different in other cell lines (MCF-7
      breast cancer cells, HT29 gut cells), which have PI3K activating mutations, that
      were examined to establish experimental parameters. In Caco2BB cells, the
      divergent effects of OT upon pAkt phosphoisoforms suggests separate sub-pathways;
      pAkt (T308) activation depends on OTR via the PI3K pathway and pAkt(S473)
      presumably results from its specific kinase mTORC2 (mammalian target of rapamycin
      complex 2). Thus, OT may modulate gut cell functions downstream of mTOR complexes
      (e.g., translation control as suggested by others in uterine cells). We will next
      explore OT-stimulated kinase activities downstream of mTOR related to pAkt
      phosphoisoforms.

PMID- 21732408
TI  - Effect of dual-specificity protein phosphatase 5 on pluripotency maintenance and
      differentiation of mouse embryonic stem cells.
AB  - The MAPK/Erk signaling pathway is considered as a key regulator of the
      pluripotency and differentiation of embryonic stem (ES) cells, while dual
      specificity protein phosphatases (DUSPs) are negative regulators of MAPK.
      Although DUSPs are potential embryogenesis regulators, their functions in the
      regulation of ES cell differentiation have not been demonstrated. The present
      study revealed that Dusp5 was expressed in mouse ES (mES) cells and that its
      expression was correlated with the undifferentiated state of these cells.
      Exogenous Dusp5 expression enhanced mES cell clonogenicity and suppressed mES
      cell differentiation by maintaining Nanog expression via the inhibition of the
      Erk pathway. Following Dusp5 knockdown, Nanog and Oct4 expression was
      significantly attenuated and the Erk signaling pathway was activated.
      Additionally, EBs derived from Dusp5 knockdown mES cells (KDEBs) exhibited a weak
      adherence capability, very little outgrowth, and a reduction in the number of
      epithelial-like cells. The expression of Gata6 (an endodermal marker) and Flk1
      and Twist1 (mesodermal markers) was inhibited in KDEBs, which indicated that
      Dusp5 influenced the differentiation of these germ layers during EB development.
      Collectively, this study suggested that Dusp5 plays an important role in the
      maintenance of pluripotency in mES cells, and that Dusp5 may be required for EB
      development.

PMID- 21732409
TI  - Resolution of inflammation by N-arachidonoylglycine.
AB  - N-arachidonoylglycine (NAgly) is an endogenous signaling lipid that is a member
      of the eicosanoid super family and is related to anandamide. It shows anti
      inflammatory activity in vivo in the mouse peritonitis model where it reduces
      migration of inflammatory leukocytes following injection of pro-inflammatory
      agents into the peritoneal cavity. Using cell culture models, including GPR18
      transfected HEK-293 cells, evidence is presented that the orphan receptor GPR18
      is involved in this action. Increases in free arachidonic acid, and robust
      stimulation of anti-inflammatory eicosanoids were observed at low micromolar
      concentrations. These included 15-deoxy-delta-13,14-PGJ(2) and lipoxin A(4) both
      of which are believed to mediate the resolution stage of inflammation. It was
      further shown that NAgly might act via GPR18 activation in promoting the number
      of Trypan Blue stained cells, a possible indicator of programmed cell death.
      Thus, we hypothesize that NAgly induces the death of inflammatory cells, a
      process that is considered to be important for the resolution of inflammation.

PMID- 21732410
TI  - The number of the genes in a functional category matters during rat liver
      regeneration after partial hepatectomy.
AB  - Rat liver regeneration after partial hepatectomy (PH) is a good model to study
      the regulation of cell proliferation. We isolated hepatocytes from regenerating
      liver at different time points after PH and used microarray Rat Genome 230 2.0
      chip to analyze the functional profiles of all up- or down-regulated genes
      manually and with automatic gene ontological tools. We found that the transcript
      expressions of PH and sham operation group were apparently different. For PH
      group, in the priming phase (2-12  h), signaling, transcription, response to
      stimulus genes predominated in up-regulated genes; in the proliferation phase (24
      72 h), cell proliferation genes predominated; in the termination phase (120-168 
      h), differentiation and translation genes predominated; while metabolism genes
      predominated in the down-regulated genes at all time points (2-168  h). These
      functional profiles are consistent with the cellular and molecular phenomenon
      observed during liver regeneration, and can be closely connected with the
      biological process. Moreover, the results indicated that not only the quantity of
      specific genes but also the number of the genes in the specific functional
      category was regulated during liver regeneration, which means the number of
      similar genes in a specific functional category matters as well as the regulation
      of the genes. The changes of the number of the regulated cell proliferation genes
      and metabolism genes during liver regeneration were similar to the expression
      patterns of some cell division genes and metabolism genes.

PMID- 21732411
TI  - Protein kinase CK2 promotes cancer cell viability via up-regulation of
      cyclooxygenase-2 expression and enhanced prostaglandin E2 production.
AB  - Augmented expression of protein kinase CK2 is associated with hyperproliferation
      and resistance to apoptosis in cancer cells. Effects of CK2 are at least
      partially linked to signaling via the Wnt/beta-catenin pathway, which is
      dramatically enhanced in colon cancer. Cyclooxygenase-2 (COX-2), a Wnt/beta
      catenin target gene, has been associated with enhanced cancer progression and
      metastasis. However, the possibility that a connection may exist between CK2 and
      COX-2 has not been explored previously. Here we investigated changes in COX-2
      expression and activity upon CK2 modulation and evaluated how these changes
      affected cell viability. COX-2 expression and cell viability decreased upon
      selective inhibition of COX-2 with SC-791 or CK2 with 2-dimethylamino-4,5,6,7
      tetrabromo-1H-benzimidazole (DMAT), both in human colon (HT29-ATCC, HT29-US, DLD
      1) and breast (ZR-75) cancer cells, as well as in human embryonic kidney (HEK
      293T) cells. On the other hand, ectopic CK2alpha expression promoted up
      regulation of COX-2 by activating the Wnt/beta-catenin pathway in HEK-293T cells.
      Noteworthy, over-expression of either CK2alpha, beta-catenin or COX-2, as well as
      supplementation of the medium with prostaglandin E2 (PGE2), all were individually
      sufficient to overcome limitations in cell viability triggered by CK2 inhibition
      either upon addition of DMAT or over-expression of a dominant negative CK2alpha
      variant. Altogether, these findings provide new insight to the role of CK2 in
      cancer by up-regulating COX-2 expression and thereby PGE2 production.

PMID- 21732412
TI  - Deregulated HOX genes in ameloblastomas are located in physical contiguity to
      keratin genes.
AB  - The expression of the HOX gene network in mid-stage human tooth development
      mostly concerns the epithelial tooth germ compartment and involves the C and D
      HOX loci. To further dissect the HOX gene implication with tooth epithelium
      differentiation we compared the expression of the whole HOX network in human
      ameloblastomas, as paradigm of epithelial odontogenic tumors, with tooth germs.
      We identified two ameloblastoma molecular types with respectively low and high
      number of active HOX C genes. The highly expressing HOX C gene ameloblastomas
      were characterized by a strong keratinized phenotype. Locus C HOX genes are
      located on chromosome 12q13-15 in physical contiguity with one of the two keratin
      gene clusters included in the human genome. The most posterior HOX C gene, HOX
      C13, is capable to interact with hair keratin genes located on the other keratin
      gene cluster in physical contiguity with the HOX B locus on chromosome 17q21-22.
      Inside the HOX C locus, a 2.2 kb ncRNA (HOTAIR) able to repress transcription, in
      cis, along the entire HOX C locus and, in trans, at the posterior region of the
      HOX D locus has recently been identified. Interestingly both loci are deregulated
      in ameloblastomas. Our finding support an important role of the HOX network in
      characterizing the epithelial tooth compartment. Furthermore, the physical
      contiguity between locus C HOX and keratin genes in normal tooth epithelium and
      their deregulation in the neoplastic counterparts suggest they may act on the
      same mechanism potentially involved with epithelial tumorigenesis.

PMID- 21732413
TI  - Identification of specific nuclear structural protein alterations in human breast
      cancer.
AB  - Breast cancer is the most commonly diagnosed type of cancer and a major cause of
      death in women. Reliable biomarkers are urgently needed to improve early
      detection or to provide evidence of the prognosis for each individual patient
      through expression levels in tumor tissue or body fluids. This proteomic analysis
      focused on the nuclear structure of human breast cancer tissue, which has been
      shown to be a promising tool for cancer biomarker development. The nuclear matrix
      composition of human breast cancer (n = 14), benign controls (n = 2), and healthy
      controls (n = 2) was analyzed by high-resolution two-dimensional gel
      electrophoresis and mass spectrometry. Validation studies were performed in an
      individual sample set consisting of additional breast cancer tissues (n = 3) and
      additional healthy control tissues (n = 2) by one-dimensional immunoblot. In this
      setting, we identified five proteins that were upregulated in human breast cancer
      tissue, but absent in the healthy and benign controls (P < 0.001). These spots
      were also present in the investigated human breast cancer cell lines, but absent
      in the MCF10a cell line, which represents normal human epithelial breast cells.
      Two of the breast cancer-specific proteins have been confirmed to be calponin h2
      and calmodulin-like protein 5 by one-dimensional immunoblot. This is the first
      study demonstrating the expression of both proteins in human breast cancer
      tissue. Further studies are required to investigate the potential role of these
      proteins as biomarkers for early diagnosis or prognosis in human breast cancer.

PMID- 21732414
TI  - An individual-based modeling approach for evaluation of endpoint sensitivity in
      harpacticoid copepod life-cycle tests and optimization of test design.
AB  - In the present study, an individual-based model for Nitocra spinipes was
      developed and used to optimize the test design of a proposed Organisation for
      Economic Co-operation and Development test guideline for harpacticoid copepods.
      The variability between individuals was taken into account, based on measured
      data, leading to stochastic model output. Virtual experiments were performed with
      the model to analyze the endpoint sensitivity and the effect of number of
      replicates and inspection intervals on statistical power. The impact of mortality
      was evaluated; most sublethal effects could not be determined if the mortality
      was >=70%. Most sensitive to mortality was the determination of effects on brood
      size, for which the statistical power was reduced at 10% mortality. Our
      simulations show that increasing the number of replicates from 72 to 96 or 144
      has little impact on the statistical power, whereas 25 replicates disallow
      relevant endpoint detection. Furthermore, it was demonstrated that the proposed
      1D inspection interval can be shifted to a 3D interval, without losing
      statistical power. It was demonstrated that developmental endpoints have a higher
      statistical power than reproductive endpoints in the current test design. The
      present study highlights the usefulness of individual-based models for optimizing
      the experimental design. The use of such models in the development of standard
      test guidelines will lead to a faster and less resource-demanding process.

PMID- 21732415
TI  - Occurrence and endocrine effects of agrichemicals in a small Nebraska, USA,
      watershed.
AB  - The Bow Creek watershed (Nebraska, USA) is dominated by the production of beef
      cattle and row crops; therefore, surface waters are likely to receive runoff
      containing steroid hormones and pesticides. The goal of the present study was to
      determine the occurrence and endocrine effects of agrichemicals in this
      watershed. To accomplish this, four sites within the watershed-Pearl, Bow, and
      East Bow Creeks and a site at the confluence with the Missouri River-were
      selected. In June of 2008, polar organic chemical integrative samplers (POCIS)
      were deployed at each site, whereas in June of 2009, water and sediment samples
      were collected. Caged fathead minnows (Pimephales promelas) were deployed at all
      of the selected sites in both years. Analysis of these samples revealed that
      steroid hormones were not present; however, pesticides were present in POCIS
      extracts and water samples. In general, the amount of pesticides was higher in
      POCIS retrieved from Pearl and Bow Creeks than in POCIS from East Bow Creek and
      the confluence. This variation between sites appeared to be related to row crop
      density, as row crop land cover surrounding the Pearl and Bow Creek sites was
      higher than that surrounding the East Bow and confluence sites. To determine the
      endocrine effects of agrichemicals within this watershed, the hepatic mRNA
      expression of vitellogenin and estrogen receptor alpha (ERalpha), as well as the
      gonadal expression of P450 aromatase A, was determined for the caged minnows.
      Females deployed at East Bow Creek and the confluence experienced decreases in
      the expression of ERalpha, suggesting that these females had been defeminized;
      however, this defeminization could not be attributed to any of the pesticides
      detected at these sites.

PMID- 21732416
TI  - Evaluation of influence of sediment on the sensitivity of a unionid mussel
      (Lampsilis siliquoidea) to ammonia in 28-day water exposures.
AB  - A draft update of the U.S. Environmental Protection Agency ambient water quality
      criteria (AWQC) for ammonia substantially lowers the ammonia AWQC, primarily due
      to the inclusion of toxicity data for freshwater mussels. However, most of the
      mussel data used in the updated AWQC were generated from water-only exposures and
      limited information is available on the potential influence of the presence of a
      substrate on the response of mussels in laboratory toxicity tests. Our recent
      study demonstrated that the acute sensitivity of mussels to ammonia was not
      influenced by the presence of substrate in 4-d laboratory toxicity tests. The
      objective of the current study was to determine the sensitivity of mussels to
      ammonia in chronic 28-d water exposures with the sediment present (sediment
      treatment) or absent (water-only treatment). The chronic toxicity test was
      conducted starting with two-month-old juvenile mussels (fatmucket, Lampsilis
      siliquoidea) in a flow-through diluter system, which maintained consistent pH
      (~8.3) and six concentrations of total ammonia nitrogen (N) in overlying water
      and in sediment pore water. The chronic value (ChV, geometric mean of the no
      observed-effect concentration and the lowest-observed-effect concentration) was
      0.36 mg N/L for survival or biomass in the water-only treatment, and was 0.66 mg
      N/L for survival and 0.20 mg N/L for biomass in the sediment treatment. The 20%
      effect concentration (EC20) for survival was 0.63 mg N/L in the water-only
      treatment and was 0.86 mg N/L in the sediment treatment (with overlapping 95%
      confidence intervals; no EC20 for biomass was estimated because the data did not
      meet the conditions for any logistic regression analysis). The similar ChVs or
      EC20s between the water-only treatment and the sediment treatment indicate that
      the presence of sediment did not substantially influence the sensitivity of
      juvenile mussels to ammonia in the 28-d chronic laboratory water exposures.

PMID- 21732417
TI  - Thinking about our every day miracle.

PMID- 21732418
TI  - Two-year effects of an interdisciplinary intervention on recovery following hip
      fracture in older Taiwanese with cognitive impairment.
AB  - OBJECTIVE: This article aims to evaluate the long-term effects of an
      interdisciplinary intervention program on cognitively impaired older persons
      after hip fracture in Taiwan. METHODS: Of 160 subjects randomly assigned to
      control (n = 81) and intervention (n  =  79) groups, 24 (29.6%) and 27 (34.2%)
      were cognitively impaired in the control and intervention groups, respectively,
      and outcomes were followed for 2 years after discharge. RESULTS: Among
      cognitively impaired subjects, more in the intervention group recovered their
      previous walking ability (odds ratio [OR] =3.49; confidence interval [CI] = 1.64
      to 7.42), activities of daily life performance (beta  =  18.59; p = 0.0002), and
      more were readmitted to the hospital (OR  =  4.44, CI  =  1.53 to 12.89) than
      those in the control group during the first 2 years following discharge. Among
      subjects without cognitive impairment, more in the intervention group recovered
      their previous walking ability (OR  =  2.6; CI  =  1.33 to 5.07), had fewer falls
      (OR  =  0.47; CI  =  0.25 to 0.86), and made fewer emergency room visits (OR  = 
      0.33; CI = 0.11 to 0.97) during the first 2 years following discharge than those
      in the control group. CONCLUSIONS: Cognitively impaired individuals benefited
      from our interdisciplinary intervention by improving their walking ability and
      physical function during the first 2 years following discharge. Specific
      strategies on fall prevention following hip fracture need to be further developed
      for cognitively impaired individuals.

PMID- 21732419
TI  - Abundance and functional roles of intrinsic disorder in allergenic proteins and
      allergen representative peptides.
AB  - The pathological process of allergies generally involves an initial activation of
      certain immune cells, tied to an ensuing inflammatory reaction on renewed contact
      with the allergen. In IgE-mediated hypersensitivity, this typically occurs in
      response to otherwise harmless food- or air-borne proteins. As some members of
      certain protein families carry special properties that make them allergenic,
      exploring protein allergens at the molecular level is instrumental to an improved
      understanding of the disease mechanisms, including the identification of relevant
      antigen features. For this purpose, we inspected a previously identified set of
      allergen representative peptides (ARPs) to scrutinize protein intrinsic disorder.
      The resulting study presented here focused on the association between these ARPs
      and protein intrinsic disorder. In addition, the connection between the disorder
      enriched ARPs and UniProt functional keywords was considered. Our analysis
      revealed that ~ 20% of the allergen peptides are highly disordered, and that ~
      77% of ARPs are either located within disordered regions of corresponding
      allergenic proteins or show more disorder/flexibility than their neighbor
      regions. Furthermore, among the subset of allergenic proteins, ~ 70% of the
      predicted molecular recognition features (MoRFs that consist of short interactive
      disordered regions undergoing disorder-to-order transitions at interaction with
      binding partners) were identified as ARPs. These results suggest that intrinsic
      disorder and MoRFs may play functional roles in IgE-mediated allergy.

PMID- 21732420
TI  - Mutational analysis of domain antibodies reveals aggregation hotspots within and
      near the complementarity determining regions.
AB  - High-affinity antibodies are critical for numerous diagnostic and therapeutic
      applications, yet their utility is limited by their variable propensity to
      aggregate either at low concentrations for antibody fragments or high
      concentrations for full-length antibodies. Therefore, determining the sequence
      and structural features that differentiate aggregation-resistant antibodies from
      aggregation-prone ones is critical to improving their activity. We have
      investigated the molecular origins of antibody aggregation for human V(H) domain
      antibodies that differ only in the sequence of the loops containing their
      complementarity determining regions (CDRs), yet such antibodies possess
      dramatically different aggregation propensities in a manner not correlated with
      their conformational stabilities. We find the propensity of these antibodies to
      aggregate after being transiently unfolded is not a distributed property of the
      CDR loops, but can be localized to aggregation hotspots within and near the first
      CDR (CDR1). Moreover, we have identified a triad of charged mutations within CDR1
      and a single charged mutation adjacent to CDR1 that endow the poorly soluble
      variant with the desirable biophysical properties of the aggregation-resistant
      antibody. Importantly, we find that several other charged mutations in CDR1, non
      CDR loops and the antibody scaffold are incapable of preventing aggregation. We
      expect that our identification of aggregation hotspots that govern antibody
      aggregation within and proximal to CDR loops will guide the design and selection
      of antibodies that not only possess high affinity and conformational stability,
      but also extreme resistance to aggregation.

PMID- 21732421
TI  - Statistical mechanics-based method to extract atomic distance-dependent
      potentials from protein structures.
AB  - In this study, we have developed a statistical mechanics-based iterative method
      to extract statistical atomic interaction potentials from known, nonredundant
      protein structures. Our method circumvents the long-standing reference state
      problem in deriving traditional knowledge-based scoring functions, by using rapid
      iterations through a physical, global convergence function. The rapid convergence
      of this physics-based method, unlike other parameter optimization methods,
      warrants the feasibility of deriving distance-dependent, all-atom statistical
      potentials to keep the scoring accuracy. The derived potentials, referred to as
      ITScore/Pro, have been validated using three diverse benchmarks: the high
      resolution decoy set, the AMBER benchmark decoy set, and the CASP8 decoy set.
      Significant improvement in performance has been achieved. Finally, comparisons
      between the potentials of our model and potentials of a knowledge-based scoring
      function with a randomized reference state have revealed the reason for the
      better performance of our scoring function, which could provide useful insight
      into the development of other physical scoring functions. The potentials
      developed in this study are generally applicable for structural selection in
      protein structure prediction.

PMID- 21732422
TI  - Invertebrate glia. Introduction.

PMID- 21732424
TI  - Roles of glial cells in neural circuit formation: insights from research in
      insects.
AB  - Investigators over the years have noted many striking similarities in the
      structural organization and function of neural circuits in higher invertebrates
      and vertebrates. In more recent years, the discovery of similarities in the
      cellular and molecular mechanisms that guide development of these circuits has
      driven a revolution in our understanding of neural development. Cellular
      mechanisms discovered to underlie axon pathfinding in grasshoppers have guided
      productive studies in mammals. Genes discovered to play key roles in the
      patterning of the fruitfly's central nervous system have subsequently been found
      to play key roles in mice. The diversity of invertebrate species offers to
      investigators numerous opportunities to conduct experiments that are harder or
      impossible to do in vertebrate species, but that are likely to shed light on
      mechanisms at play in developing vertebrate nervous systems. These experiments
      elucidate the broad suite of cellular and molecular interactions that have the
      potential to influence neural circuit formation across species. Here we focus on
      what is known about roles for glial cells in some of the important steps in
      neural circuit formation in experimentally advantageous insect species. These
      steps include axon pathfinding and matching to targets, dendritic patterning, and
      the sculpting of synaptic neuropils. A consistent theme is that glial cells
      interact with neurons in two-way, reciprocal interactions. We emphasize the
      impact of studies performed in insects and explore how insect nervous systems
      might best be exploited next as scientists seek to understand in yet deeper
      detail the full repertory of functions of glia in development.

PMID- 21732423
TI  - The glia of Caenorhabditis elegans.
AB  - Glia have been, in many ways, the proverbial elephant in the room. Although glia
      are as numerous as neurons in vertebrate nervous systems, technical and other
      concerns had left research on these cells languishing, whereas research on
      neurons marched on. Importantly, model systems to study glia had lagged
      considerably behind. A concerted effort in recent years to develop the canonical
      invertebrate model animals, Drosophila melanogaster and Caenorhabditis elegans,
      as settings to understand glial roles in nervous system development and function
      has begun to bear fruit. In this review, we summarize our current understanding
      of glia and their roles in the nervous system of the nematode C. elegans. The
      recent studies we describe highlight the similarities and differences between C.
      elegans and vertebrate glia, and focus on novel insights that are likely to have
      general relevance to all nervous systems.

PMID- 21732425
TI  - Trophic neuron-glia interactions and cell number adjustments in the fruit fly.
AB  - Trophic interactions between neurons and enwrapping glia, and between neurons and
      target cells, provide plasticity to the mammalian nervous system. Here, we review
      evidence that analogous cell interactions operate in the development of the
      nervous system of the fruit-fly Drosophila. Homologues of the canonical mammalian
      trophic factors also maintain neuronal and glial survival in Drosophila,
      adjusting cell populations to enable appropriate function, and revealing
      commonalities in nervous system development across the animals. There are also
      differences between neuron-glia interactions in flies and humans, not
      surprisingly, because we are only related to flies through a remote common
      ancestor. Nevertheless, the shared cellular and molecular mechanisms underlying
      developmental plasticity and enwrapping glial functions, strengthen the
      opportunity to use Drosophila to understand the brain, to model brain diseases
      and to understand the involvement of glial cells in nervous system regeneration.

PMID- 21732427
TI  - Glial solute carrier transporters in Drosophila and mice.
AB  - Glia regulate brain physiology primarily by regulating the movement and
      concentration of substances in the extracellular fluid. Therefore, one approach
      to understanding the role of glia in brain physiology is to study what happens
      when glial transporters are removed or modified. The largest and most highly
      conserved class of transporter is solute carrier (SLC) proteins. SLC proteins are
      highly expressed in brain, and many are found in glia. The function of many SLC
      proteins in the brain--particularly in glia--is very poorly understood. SLC
      proteins can be relatively easily knocked out or modified in genetic model
      organisms to better understand glial function. Drosophila are popular genetic
      model organisms that offer a nice balance between genetic malleability and brain
      complexity. They are ideal for such an endeavor. This article lists and discusses
      SLC transporter family members that are expressed in both mouse and Drosophila
      glia, in an effort to provide a foundation for studies of glial SLC transporters
      using Drosophila as a model.

PMID- 21732426
TI  - Glial cell modulation of circadian rhythms.
AB  - Studies of Drosophila and mammals have documented circadian changes in the
      morphology and biochemistry of glial cells. In addition, it is known that
      astrocytes of flies and mammals contain evolutionarily conserved circadian
      molecular oscillators that are similar to neuronal oscillators. In several
      sections of this review, I summarize the morphological and biochemical rhythms of
      glia that may contribute to circadian control. I also discuss the evidence
      suggesting that glia-neuron interactions may be critical for circadian timing in
      both flies and mammals. Throughout the review, I attempt to compare and contrast
      findings from these invertebrate and vertebrate models so as to provide a
      synthesis of current knowledge and indicate potential research avenues that may
      be useful for better understanding the roles of glial cells in the circadian
      system.

PMID- 21732428
TI  - SBA-15-type organosilica with 4-mercapto-N,N-bis-(3-Si-propyl)butanamide for
      palladium scavenging and cross-coupling catalysis.
AB  - This work describes the synthesis of novel functional silica materials with
      difunctional thiol-amide substructures and featuring regular architectures on a
      mesoscopic level. The functional materials were synthesised by both one-pot co
      condensation and post-grafting approaches. The thiol groups confined in the
      matrix were found to be efficient for palladium entrapment, leading to highly
      active and reusable heterogeneous catalysts for Sonogashira and Suzuki-Miyaura
      cross-coupling reactions. This work evidences the crucial role of both the thiol
      precursor and the condensation degree of the silica scaffold in view of the
      design of stable and reusable tailor-made mesoporous catalytic silica materials.

PMID- 21732429
TI  - Cubic and hexagonal mesoporous carbon in the pores of anodic alumina membranes.
AB  - Cubic and circular hexagonal mesoporous carbon phases in the confined environment
      of the pores of anodic alumina membranes (AAM) were obtained by organic-organic
      self-assembly of a preformed oligomeric resol precursor and the triblock
      copolymer templates Pluronic F127 or P123, respectively. Casting and solvent
      evaporation were followed by self-assembly and the formation of a condensed wall
      material by thermopolymerization of the precursor oligomers, thus resulting in
      mesostructured phenolic resin phases. Subsequent thermal decomposition of the
      surfactant and carbonization were achieved through thermal treatment at
      temperatures up to 1000  degrees C under an inert atmosphere. The resulting
      hierarchical mesoporous composite materials were characterized by small-angle X
      ray scattering and nitrogen-sorption measurements. The structural features were
      directly imaged in TEM cross-sections of the composite membranes. For both
      structures, the AAM pores were completely filled and no shrinkage was observed
      due to strong adhesion of the carbon-wall material to the AAM pore walls. As a
      consequence, the pore size of the mesophase system stays almost constant even
      after thermal treatment at 1000  degrees C.

PMID- 21732430
TI  - Two-step electrochemically directed synthesis of Pr4N(TCNQ)n (n=1, 2):
      preparation, structure, and properties of a magnetically isolated dimer and a
      quasi-one-dimensional chain.
AB  - Solid-state electrochemistry of a tetracyanoquinodimethane (TCNQ)-modified
      electrode in contact with a tetrapropylammonium cation (Pr(4)N(+)) electrolyte
      showed two electron-transfer steps to give Pr(4)N(TCNQ)(2) (1) and Pr(4)N(TCNQ)
      (2) rather than the traditional one-electron step to directly give Pr(4)N(TCNQ).
      Two thermodynamically stable Pr(4)N(+)-TCNQ stoichiometries, 1 and 2, were
      synthesized and characterized. The degree of charge transfer (rho) calculated
      from the crystal structure is -0.5 for the TCNQ moieties in 1 and -1.0 for those
      in 2. Raman spectra for Pr(4)N(TCNQ)(2) show only one resonance for the
      extracyclic C=C stretching at 1423 cm(-1), which lies approximately midway
      between that of TCNQ at 1454 cm(-1) and TCNQ(-) at 1380 cm(-1). Both the magnetic
      susceptibility and EPR spectra are temperature-dependent, with a magnetic moment
      close to that for one unpaired electron per (TCNQ)(2) unit in 1, whereas 2 is
      almost diamagnetic. Pressed discs of both complexes show conductivity (1-2*10(-5)
      S cm(-1)) in the semiconductor range. For 1, the position of zero current for the
      steady-state voltammograms implies 50% of TCNQ(-) and 50% TCNQ(0) is present in
      solution, thereby supporting a dissociation of (TCNQ)(2)(-) in solution, but is
      indicative of only TCNQ(-) being present for 2.

PMID- 21732431
TI  - Self-assembly of supramolecular architectures and polymers by orthogonal metal
      complexation and hydrogen-bonding motifs.
AB  - A modular construction kit with two orthogonal noncovalent binding sites for self
      assembly of supramolecular architectures is presented. The heteroditopic building
      blocks contain a terpyridine (tpy) unit for coordination of metal ions and a
      Hamilton receptor for multiple H-bonding of cyanuric acid derivatives. The
      association constants of ligand binding of M(II) complexes (M=Ru, Zn, Fe, and Pt)
      with a dendritic end cap were determined to be in the range of 10(2) and 10(4) L
      mol(-1) in chloroform. The capabilities for binding of metal ions were
      investigated by (1)H NMR and UV/Vis spectroscopy. The Fe complexes are most
      appropriate for the generation of discrete and high-ordered architectures due to
      their strong tendency to form FeL(2) complexes. Superstructures are readily
      formed in a one-pot procedure at room temperature. No mutual interactions between
      the orthogonal binding motifs were observed, and this demonstrates the highly
      specific nature of each binding process. Decomplexation experiments were carried
      out to examine the reversibility of Fe-tpy coordination. Substitution of the
      terminal end cap with a homoditopic bis-cyanurate linkage leads to formation of
      an iron-containing supramolecular strand. Formation of coordination polymers was
      confirmed by viscosity measurements. The supramolecular polymer strands can be
      reversibly cleaved by addition of a terminating cyanuric acid building block, and
      this proves the dynamic nature of this noncovalent polymerization process.

PMID- 21732432
TI  - Structure, magnetism and theory of a family of nonanuclear Cu(II)5Ln(III)4
      triethanolamine clusters displaying single-molecule magnet behaviour.
AB  - Synthesis, crystal structures and magnetic studies are reported for four new
      heterometallic Cu(II)-Ln(III) clusters. The reaction of Cu(NO(3))(2).3H(2)O with
      triethanolamine (teaH(3)), pivalic acid, triethylamine and Ln(NO(3))(3).6H(2)O
      (Ln=Gd, Tb, Dy and Ho) results in the formation of four isostructural nonanuclear
      complexes of general formula
      [Cu(II)(5)Ln(III)(4)O(2)(teaH)(4){O(2)CC(CH(3))(3)}(2)(NO(3))(4)(OMe)(4)].2MeOH.2
      t(2)O [Ln=Gd (1), Tb (2), Dy (3) and Ho (4)]. The metal core of each cluster is
      made up of four face- and vertex-sharing tetrahedral units. Solid-state DC
      magnetic susceptibility studies reveal competing anti- and ferromagnetic
      interactions within each cluster leading to large-spin ground states for 1-4.
      Solid-state AC magnetic susceptibility studies show frequency-dependent out-of
      phase (chi''(M)) signals for 2-4 below 4 K, suggestive of single-molecule magnet
      behaviour. Ab initio calculations on one of the anisotropic examples (3) provided
      a rare set of J values for Dy-Cu and Cu-Cu exchange interactions (Dy-Dy zero),
      some ferro- and some antiferromagnetic in character, that explain its magnetic
      behaviour.

PMID- 21732433
TI  - The role of electronic coupling in linear porphyrin arrays probed by single
      molecule fluorescence spectroscopy.
AB  - Single-molecule photophysical properties of two families of linear porphyrin
      arrays have been investigated by single-molecule fluorescence detection
      techniques. Butadiyne-linked arrays (Z(N)B) with extensive pi-conjugation perform
      as photostable one-quantum systems. This demonstration has been suggested by the
      long-lasting initial emissive state and subsequent discrete one-step
      photobleaching in the fluorescence intensity trajectories (FITs). As in the
      behavior of a one-quantum system, Z(N)B shows anti-bunching data in the
      coincidence measurements. On the other hand, in directly-linked arrays (Z(N))
      with strong dipole coupling, each porphyrin moiety keeps individual character in
      photobleaching dynamics. The stepwise photobleachings in the FITs account for
      this explanation. Most of the FITs of Z(N) do not carry momentary cessation of
      fluorescence emission, which has been explained by the strongly bound electron
      hole pair of Frenkel exciton that suppresses charge transfer between the molecule
      and surrounding polymers. These results give insight into the influences of
      interchromophorinc interactions between porphyrin moieties in the multiporphyrin
      arrays on their fluorescence dynamics at the single-molecule level.

PMID- 21732434
TI  - Intramolecular weak interactions in the thermodynamic stereoselectivity of
      copper(II) complexes with carnosine-trehalose conjugates.
AB  - The interactions of metal ions with chiral molecules are of particular interest
      for relevant biochemical processes, as many of them are made possible only with a
      selected chirality of the stereocenters. In this work we report a study of the
      stereoselectivity of copper(II) complexes with D-trehalose-L-carnosine and D
      trehalose-D-carnosine as a prototypical case of natural chirality selection. The
      interest in L-carnosine dipeptide is compounded by its antioxidant and antitumor
      properties, which are further enhanced when combined with D-trehalose.
      Potentiometric, calorimetric, and UV/circular dichroism (CD) spectroscopic
      measurements show that the copper(II) dimer of D-trehalose-L-carnosine is more
      stable than the D-trehalose-D-carnosine diastereoisomeric copper(II) dimer (log
      beta(L)(22-2) - log beta(D)(22-2) = 3.6). Free-energy calculations highlight that
      the cause of this different behavior lies with different intramolecular weak
      interactions between the diastereoisomers. The different pattern of hydrogen
      bonds and the different CH-pi interactions between the pi-electron-rich imidazole
      and the alpha-glucose rings are more favorable by 5 kcal mol(-1) in the L dimer.

PMID- 21732435
TI  - Design and synthesis of iridium bis(carbene) complexes for efficient blue
      electrophosphorescence.
AB  - Five iridium bis(carbene) complexes, [Ir(pmi)(2)(pypz)] (1), [Ir(mpmi)(2)(pypz)]
      (2), [Ir(fpmi)(2)(pypz)] (3), [Ir(fpmi)(2)(pyim)] (4), and [Ir(fpmi)(2)(tfpypz)]
      (5) (pmi=1-phenyl-3-methylimdazolin-2-ylidene-C,C(2'); fpmi=1-(4-fluorophenyl)-3
      methylimdazolin-2-ylidene-C,C(2'); mpmi=1-(4-methyl-phenyl)-3-methylimdazolin-2
      ylidene-C,C(2'); pypz=2-(1H-pyrazol-5-yl)pyridinato; pyim=2-(1H-imidazol-2
      yl)pyridinato; and tfpypz=2-(3-(trifluoromethyl)-1H-pyrazol-5-yl)pyridinato),
      were synthesized and their structures were characterized by NMR spectroscopy,
      mass spectroscopy and X-ray diffraction. These complexes showed phosphorescent
      emission with the emission maxima between 453 and 490 nm. Various
      spectrophotometric measurements, cyclic voltammetric studies, and density
      functional theory (DFT) calculations show that, unlike most of the phosphorescent
      cyclometalated iridium complexes, the lowest unoccupied molecular orbital (LUMO)
      energy and the emissive state of these iridium complexes are mainly controlled by
      the N,N'-heteroaromatic (N^N) ligand. Despite the fact that the LUMO levels of
      these complexes are mainly on the N^N ligands, the efficiencies of the
      electroluminescent (EL) devices are very high. For example, the EL devices using
      [Ir(mpmi)(2)(pypz)], [Ir(fpmi)(2)(pypz)], and [Ir(fpmi)(2)(tfpypz)] as the dopant
      emitters exhibited light- to deep-blue electrophosphorescence with external
      quantum efficiencies of 15.2, 14.1, and 7.6% and Commission Internationale
      d'Enclairage (x,y) coordinates (CIE(x,y)) of (0.14, 0.27), (0.14, 0.18) and
      (0.14, 0.10), respectively.

PMID- 21732436
TI  - On the reactions of methyl radicals with TiO2 nanoparticles and granular powders
      immersed in aqueous solutions.
AB  - Methyl radicals react with TiO(2) nanoparticles (NPs) immersed in aqueous
      solutions to form transients in which the methyls are covalently bound to the
      particles. The rate constant for this reaction approaches the diffusion
      controlled limit and increases somewhat with the number of methyls bound to the
      particle. The transients decompose to yield ethane. Thus, formally the particles
      "catalyse" the dimerization of the radicals, a reaction that is diffusion
      controlled. Rutile powders behave similarly to the TiO(2) NPs whereas the
      mechanism for the decomposition of the transients formed in the analogous
      reaction of the radicals with anatase powders differs. These results are of
      importance as alkyl radicals are formed near the surface of TiO(2) in a variety
      of important photocatalytic processes. The results imply that the reactions of
      alkyl radicals with TiO(2) have to be considered in these processes.

PMID- 21732437
TI  - Synthesis of mesoporous Pt nanoparticles with uniform particle size from aqueous
      surfactant solutions toward highly active electrocatalysts.
AB  - Pores for improved catalysis: Mesoporous Pt nanoparticles (MPNs) with large
      surface areas are created within 10 min by a very simple, one-step, aqueous
      reaction at room temperature. The obtained MPNs exhibit significantly enhanced
      catalytic activity toward the methanol oxidation reaction.

PMID- 21732438
TI  - Moderate and advanced intramolecular proton transfer in urea-anion hydrogen
      bonded complexes.
AB  - The study of the interactions of the three urea-based receptors AH, BH(+) and
      CH(2+) with a variety of anions, in MeCN, has made it possible to verify the
      current view that hydrogen bonding is frozen proton transfer from the donor (the
      urea N-H fragment in this case) to the acceptor (the anion X(-)). The poorly
      acidic, neutral receptor AH establishes two equivalent hydrogen bonds N-H...X(-),
      with all anions, including CH(3)COO(-) and F(-), in which moderate proton
      transfer from N-H to the anion takes place. The strongly acidic, dicationic
      receptor CH(2+) forms, with most anions, complexes in which two inequivalent
      hydrogen bonds are present: one involving moderate proton transfer (N-H...X(-))
      and one in which advanced proton transfer has taken place, described as N(-)...H
      X. The degree of proton advancement is directly related to the basic tendencies
      of the anion. The cationic receptor BH(+) of intermediate acidic properties only
      forms complexes with two inequivalent hydrogen bonds (moderate+advanced proton
      transfer) with CH(3)COO(-) and F(-), and complexes with two equivalent hydrogen
      bonds (moderate proton transfer) with all the other anions. Moreover, [B...HF]
      and [C...HF](+), on addition of a second F(-) ion, lose the bound HF molecule to
      give HF(2)(-). Release of CH(3)COOH, with the formation of
      [CH(3)COOH...CH(3)COO](-), also takes place with the [B...CH(3)COOH] complex in
      the presence of a large excess of anion.

PMID- 21732439
TI  - Inelastic neutron scattering on an Mn10 supertetrahedron: assessment of exchange
      coupling constants, ferromagnetic spin waves and an analogy to the Huckel method.
AB  - The synthesis, crystal structure and magnetic characterisation by magnetisation
      and inelastic neutron scattering (INS) of a mixed-valent Mn(10) supertetrahedral
      aggregate [Mn(III)(6)Mn(II)(4)(MU(4)-O)(4)(MU(3)-N(3))(3)(MU(3)
      Br)(Hmpt)(6)(Br)]Br(0.7)(N(3))(0.3).2MeOH.3MeCN (1) (H(3)mpt=3-methylpentan-1,3,5
      triol) is reported. The magnetic core of the molecule can be described as an
      octahedron of six S=2 Mn(III) ions with four faces, each capped by a S=5/2 Mn(II)
      ion such as to form the supertetrahedron. Unlike most related complexes, the
      molecular symmetry is slightly reduced from approximately T(d) to C(3). The
      magnetic data reveal a total spin of S=22 in the ground state due to
      ferromagnetic exchange couplings within the molecule. The combined INS and
      magnetic data permits the accurate determination of the exchange coupling
      constants. Two types are found. The couplings between the Mn(III) ions in the
      inner octahedron are characterised by J(a)=18.4(3) K, whereas the couplings
      between the apical Mn(II) ions to the neighbouring Mn(III) ions are given by
      J(b)=7.3(2) K. The significantly larger coupling strength J(a) as compared to
      J(b), and the near-T(d) symmetry have profound consequences on the energy
      spectrum, which are discussed and carefully analysed. In particular, the observed
      INS spectra can consistently be reproduced by a simplified model in which the
      inner octahedron is replaced by one large spin of length S(0)=12. This model
      provides intuitive insight into the structure of the magnetic spectrum.
      Additionally, the magnetic excitations at low temperature are analysed within the
      frame of ferromagnetic linear spin-wave theory, which permits an analytical
      calculation of the energy levels. For ferromagnetic clusters, a close analogy to
      the Huckel method of electronic structure calculation can be drawn, which allows
      one to grasp the results of the spin-wave theory or the magnetic excitation
      spectrum, respectively, in a chemical language.

PMID- 21732440
TI  - Generating hydrogen gas from methane with carbon captured as pure spheroidal
      nanomaterials.
AB  - Energy production by using hydrogen gas as a feedstock is considered to be one of
      the keys to creating clean energy, with the proviso that the gas is generated in
      a sustainable way with no emissions. A simple, self-sustaining process generating
      hydrogen gas from methane using inexpensive stainless steel wire-mesh catalysts
      at elevated temperatures (800  degrees C) is reported. A theoretical analysis of
      the production of electricity by this process revealed peak chain energy
      efficiencies up to 21% (emission free) when using a percentage of the produced
      hydrogen (approximately 40% of purified yield) as the heat source. In addition, a
      practical method has been developed to purify the carbon byproduct, affording
      essentially pure highly graphitic spheroidal carbon for advanced materials
      applications.

PMID- 21732441
TI  - Chemical surface modification of self-assembled monolayers by radical nitroxide
      exchange reactions.
AB  - This article describes the application of nitroxide exchange reactions of surface
      bound alkoxyamines as a tool for reversible chemical modification of self
      assembled monolayers (SAMs). This approach is based on radical chemistry, which
      allows for introduction of various functional groups and can be used to
      reversibly introduce functionalities at surfaces. To investigate the scope of
      this surface chemistry, alkoxyamines with different functionalities were
      synthesized and were then applied to the immobilization of, for example, dyes,
      sugars, or biotin. Surface analysis was carried out by contact angle, X-ray
      photoelectron spectroscopy, and fluorescence microscopy measurements. The results
      show that this reaction is highly efficient, reversible, and mild and allows for
      immobilization of various sensitive functional groups. In addition, Langmuir
      Blodgett lithography was used to generate structured SAMs. Site-selective
      immobilization of a fluorescent dye could be achieved by nitroxide exchange
      reactions.

PMID- 21732442
TI  - Differences in reactivity of epoxides in the copolymerisation with carbon dioxide
      by zinc-based catalysts: propylene oxide versus cyclohexene oxide.
AB  - The homogeneous dinuclear zinc catalyst going back to the work of Williams et al.
      is to date the most active catalyst for the copolymerisation of cyclohexene oxide
      and CO(2) at one atmosphere of carbon dioxide. However, this catalyst shows no
      copolymer formation in the copolymerisation reaction of propylene oxide and
      carbon dioxide, instead only cyclic carbonate is found. This behaviour is known
      for many zinc-based catalysts, although the reasons are still unidentified.
      Within our studies, we focus on the parameters that are responsible for this
      typical behaviour. A deactivation of the catalyst due to a reaction with
      propylene oxide turns out to be negligible. Furthermore, the catalyst still shows
      poly(cyclohexene carbonate) formation in the presence of cyclic propylene
      carbonate, but the catalyst activity is dramatically reduced. In
      terpolymerisation reactions of CO(2) with different ratios of cyclohexene oxide
      to propylene oxide, no incorporation of propylene oxide can be detected, which
      can only be explained by a very fast back-biting reaction. Kinetic investigations
      indicate a complex reaction network, which can be manifested by theoretical
      investigations. DFT calculations show that the ring strains of both epoxides are
      comparable and the kinetic barriers for the chain propagation even favour the
      poly(propylene carbonate) over the poly(cyclohexene carbonate) formation.
      Therefore, the crucial step in the copolymerisation of propylene oxide and carbon
      dioxide is the back-biting reaction in the case of the studied zinc catalyst. The
      depolymerisation is several orders of magnitude faster for poly(propylene
      carbonate) than for poly(cyclohexene carbonate).

PMID- 21732443
TI  - Novel multidentate sulfur-nitrogen ligands with enhanced complexation properties.
AB  - Di(tert-butyl)sulfur diimide and bis(trimethylsilyl)sulfur diimide were reacted
      with different metalated amines to form versatile novel multidentate ligand
      systems with side-arm donation. Their complexation properties in terms of ligand
      design, denticity and the cation size are discussed. We report herein the
      synthesis and structure elucidation of
      [(tBuN)(2)S{LiMe(2)N(C(6)H(4))S(NtBu)(2)}(2)] (1),
      [(Li{Me(2)N(C(6)H(4))S(NSiMe(3))(2)})(2)] (2),
      [(Li(thf){Me(2)N(C(6)H(4))S(NSiMe(3))(2)})(2)] (3), [(Li{2
      PicS(NSiMe(3))(2)})(2)] (4), [(Li{Me(2)N(CH(2))(2)N(Me)S(NSiMe(3))(2)})(2)] (5),
      [(Na{Me(2)N(CH(2))(2)N(Me)S(NSiMe(3))(2)})(2)] (6) and
      [(K{Me(2)N(C(6)H(4))S(NSiMe(3))(2)})(2)] (7).

PMID- 21732444
TI  - Theoretical and X-ray crystallographic evidence of a fluorine-imine gauche
      effect: an addendum to Dunathan's stereoelectronic hypothesis.
AB  - The preference of beta-fluoroimines to adopt a gauche conformation has been
      studied by single-crystal X-ray diffraction analysis and DFT methods. Empirical
      and theoretical evidence for a preferential gauche arrangement around the NCCF
      torsion angle (phi) is presented ((E)-2-fluoro-N-(4-nitrobenzylidene)ethanamine:
      phi(NCCF) =70.0 degrees ). In the context of this study, the analysis of a
      pyridoxal-derived beta-fluoroaldimine was performed, a species that is implicated
      in the inhibition of pyridoxal phosphate (PLP)-dependent enzymes by beta
      fluoroamine derivatives. The gauche preference of the internal aldimine
      (=NCH(2)CH(2)F) that can be rationalized by stereoelectronic arguments does not
      hold for the corresponding external system (N=CHCH(2)F) (E(min) when phi(NCCF)
      =120 degrees ). Moreover, the C-F bond is lengthened by more than 0.02 A at
      phi(NCCF) =+/-90 degrees , when it is exactly antiperiplanar to the conjugated
      imine. This activation of the C-F sigma bond by an adjacent pi system constitutes
      an addendum to Dunathan's stereoelectronic hypothesis.

PMID- 21732445
TI  - Catalytic enantioselective beta-alkylation of alpha,beta-unsaturated aldehydes by
      combination of transition-metal- and aminocatalysis: total synthesis of
      bisabolane sesquiterpenes.
AB  - Branching out! The first co-catalytic enantioselective (up to 98:2 e.r.) beta
      alkylation of alpha,beta-unsaturated aldehydes by combination of simple chiral
      amine and copper catalysts provides beta-branched aldehydes in a one-pot
      protocol. The methodology was applied to the short total syntheses of bisabolane
      sesquiterpenes (S)-(+)-curcumene, (E)-(S)-(+)-3-dehydrocurcumene and (S)-(+)
      tumerone.

PMID- 21732446
TI  - An axially chiral, electron-deficient borane: synthesis, coordination chemistry,
      Lewis acidity, and reactivity.
AB  - An axially chiral dihydroborepine with a binaphthyl backbone and a C(6)F(5)
      substituent at the boron atom was prepared by transmetalation from the
      corresponding tin precursor. This novel motif was structurally characterized by X
      ray diffraction analysis as its THF and its PhCN Lewis acid/base complex. (1)H
      NMR measurements at variable temperatures of the former adduct revealed a
      remarkable dynamic behavior in solution. Several more Lewis pairs with oxygen,
      nitrogen, carbon, and phosphorus sigma-donors were synthesized and analyzed by
      multinuclear NMR spectroscopy. The determination of the borane's Lewis acidity
      with the Gutmann-Beckett method attests its substantial Lewis acidity [85% with
      Et(3) PO as well as 74% with Ph(3) PO relative to the parent B(C(6)F(5))(3)].
      Representative examples of Si-H bond activation (carbonyl reduction and
      dehydrogenative Si-O coupling) are included, demonstrating the chemical stability
      and the synthetic potential of the new chiral boron-based Lewis acid.

PMID- 21732447
TI  - Synthetic utilization of 2-chloro-1,1,1,2-tetrafluoroethane.
AB  - beta-Substituted alpha-fluoro-alpha,beta-unsaturated carboxylic acids have been
      successfully synthesized, usually in a (Z)-stereospecific manner by way of a
      stepwise or a one-pot three-step procedure starting from 2-chloro-1,1,1,2
      tetrafluoroethane (HCFC-124), one of the major byproducts of the industrial
      process for tetrafluoroethene formation from chlorofluoromethane (HCFC-22).

PMID- 21732448
TI  - Composition dependence of the photocatalytic activities of BiOCl(1-x)Br(x) solid
      solutions under visible light.
AB  - We prepared BiOCl(1-x)Br(x) (x=0-1) solid solutions and characterized their
      structures, morphologies, and photocatalytic properties by X-ray diffraction,
      diffuse reflectance spectroscopy, scanning electron microscopy, Raman
      spectroscopy, photocurrent and photocatalytic activity measurements and also by
      density functional theory calculations for BiOCl, BiOBr, BiOCl(0.5)Br(0.5). Under
      visible-light irradiation BiOCl(1-x)Br(x) exhibits a stronger photocatalytic
      activity than do BiOCl and BiOBr, with the activity reaching the maximum at x=0.5
      and decreasing gradually as x is increased toward 1 or decreased toward 0. This
      trend is closely mimicked by the photogenerated current of BiOCl(1-x)Br(x) ,
      indicating that the enhanced photocatalytic activity of BiOCl(1-x)Br(x) with
      respect to those of BiOCl and BiOBr originates from the trapping of
      photogenerated carriers. Our electronic structure calculations for
      BiOCl(0.5)Br(0.5) with the anion (O(2-), Cl(-), Br(-)) and cation (Bi(3+))
      vacancies suggest that the trapping of photogenerated carriers is caused most
      likely by Bi(3+) cation vacancies, which generate hole states above the
      conduction band maximum.

PMID- 21732449
TI  - Ruthenium-catalysed synthesis of fluorinated bicyclic amino esters through tandem
      carbene addition/cyclopropanation of enynes.
AB  - The reaction of fluorinated 1,6- and 1,7-enynes, containing the moiety
      N(PG)C(CF(3))(CO(2)R), with diazo compounds in the presence of [RuCl(cod)(Cp*)]
      (cod=cycloocta-1,5-diene, Cp*=C(5)Me(5) , PG=protecting group) as the catalyst
      precursor leads to the formation of fluorinated 3-azabicyclo[3.1.0]hexane-2
      carboxylates and 4-azabicyclo-[4.1.0]heptane-3-carboxylates. This catalytic
      transformation was applied to various protecting groups and has proved to be a
      selective and a general synthetic tool to form constrained proline or homoproline
      derivatives in good yields. Z stereoselectivity of the created alkenyl group is
      obtained with N(2)CHSiMe(3), whereas N(2)CHCO(2)Et favours selectively the E
      configuration for the same double bond. The diastereoselectivity exo/endo depends
      on the size of the created ring. The X-ray structures of two products have been
      determined, showing the stereochemistry of the compounds. The reaction can be
      understood by initial [2+2] addition of the Ru=CHY bond, generated from
      diazoalkane, with the C=CH bond of the enyne leading to a key bicyclic
      ruthenacyclobutane, which promotes the cyclopropanation, rather than metathesis.
      This selective formation of bicyclic [n.1.0] compounds results from the ruthenium
      catalysed creation of three carbon-carbon bonds in a single step under mild
      conditions.

PMID- 21732450
TI  - Amine- and sulfonamide-promoted Wittig olefination reactions in water.
AB  - Amine-promoted olefination: The reaction of a phosphonium salt and an aldehyde in
      water to yield alkenes with high E-configurational control is promoted by
      catalytic amounts of non-basic amines in aqueous bicarbonate media. Possible
      catalytic cycles involving imines and iminium intermediates are discussed.

PMID- 21732451
TI  - The organocatalytic vinylogous aldol reaction: recent advances.
AB  - Over the past decade, organocatalysis has emerged as a powerful tool for
      stereoselective carbon-carbon bond formation under exceptionally mild conditions.
      The organocatalytic versions of a large number of traditional synthetic
      transformations are now well established and the quest for new applications of
      the basic concepts of organocatalysis continues. This review addresses the
      emergent interest in the organocatalytic vinylogous aldol reaction. While
      noteworthy progress has been made in this area, significant challenges lie ahead.

PMID- 21732452
TI  - Macroscopic, free-standing Ag-reduced, graphene oxide Janus films prepared by
      evaporation-induced self-assembly.
AB  - A facile, efficient, and unique self-assembly process for the preparation of the
      macroscopic, free-standing, Ag-reduced, graphene oxide (Ag-RGO) Janus films,
      which exhibit a unique asymmetry of their two surfaces with macroscopic
      dimensions, is presented. A novel strategy using an evaporation-induced, self
      assembly (EISA) process is shown to be a powerful and flexible method for
      synthesizing well-defined Janus thin films.

PMID- 21732453
TI  - Remote communication in a DNA-based nanoswitch.
AB  - Nano-telegraph: It is shown quantum chemically how the hydrogen-bond strength of
      a DNA base pair can be remotely switched (across several nanometers) between
      three states (weak, intermediate, and strong) through a pi-conjugated "organic
      wire".

PMID- 21732454
TI  - Metabolite characterization of a novel anti-cancer agent, icotinib, in humans
      through liquid chromatography/quadrupole time-of-flight tandem mass spectrometry.
AB  - Icotinib is a novel anti-cancer drug that has shown promising clinical efficacy
      and safety in patients with non-small-cell lung cancer (NSCLC). At this time, the
      metabolic fate of icotinib in humans is unknown. In the present study, a liquid
      chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/Q-TOF MS)
      method was established to characterize metabolites of icotinib in human plasma,
      urine and feces. In addition, nuclear magnetic resonance (NMR) detection was
      utilized to determine the connection between side-chain and quinazoline groups
      for some complex metabolites. In total, 29 human metabolites (21 isomer
      metabolites) were characterized, of which 23 metabolites are novel compared to
      the metabolites in rats. This metabolic study revealed that icotinib was
      extensively metabolized at the 12-crown-4 ether moiety (ring-opening and further
      oxidation), carbon 15 (hydroxylation) and an acetylene moiety (oxidation) to
      yield 19 oxidized metabolites and to further form 10 conjugates with sulfate acid
      or glucuronic acid. To our knowledge, this is the first report of the human
      metabolic profile of icotinib. Study results indicated that significant attention
      should be paid to the metabolic profiles of NSCLC patients during the development
      of icotinib.

PMID- 21732455
TI  - Probing sites of histidine phosphorylation with iodination and tandem mass
      spectrometry.
AB  - Phosphorylation at histidine residues occurs frequently in biology, but is often
      overlooked in proteomics experiments due to extreme acid lability. A new method
      utilizing histidine labeling with iodine to record information about
      phosphorylation is described. Essentially, phosphorylated histidine residues are
      not labeled while unmodified histidine undergoes complete iodination. Iodination
      is stabile both under acidic conditions, and upon collisional activation in the
      gas phase. This enables site-specific information to be retained with standard
      liquid chromatography separations and tandem mass spectrometry by collisional
      activation. Semi-quantitative information about the relative amounts of
      phosphorylated versus unmodified states can also be easily obtained from the
      relative ion abundances. This new method should provide a pathway forward for
      analyzing histidine phosphorylation in complex systems.

PMID- 21732456
TI  - Direct identification of bacteria in blood culture by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry: a new methodological
      approach.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has recently been demonstrated to be a powerful tool for the rapid
      identification of bacteria from growing colonies. In order to speed up the
      identification of bacteria, several authors have evaluated the usefulness of this
      MALDI-TOF MS technology for the direct and quick identification bacteria from
      positive blood cultures. The results obtained so far have been encouraging but
      have also shown some limitations, mainly related to the bacterial growth and to
      the presence of interference substances belonging to the blood cultures. In this
      paper, we present a new methodological approach that we have developed to
      overcome these limitations, based mainly on an enrichment of the sample into a
      growing medium before the extraction process, prior to mass spectrometric
      analysis. The proposed method shows important advantages for the identification
      of bacterial strains, yielding an increased identification score, which gives
      higher confidence in the results.

PMID- 21732457
TI  - Multicomponent ionic complexes studied by matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry methods.

PMID- 21732459
TI  - Towards optimized MR thermometry of the human heart at 3T.
AB  - Catheter ablation using radio frequency (RF) has been used increasingly for the
      treatment of cardiac arrhythmias and may be combined with proton resonance
      frequency shift (PRFS) -based MR thermometry to determine the therapy endpoint.
      We evaluated the suitability of two different MR thermometry sequences (TFE and
      TFE-EPI) and three blood suppression techniques. Experiments were performed
      without heating, using an optimized imaging protocol including navigator
      respiratory compensation, cardiac triggering, and image processing for the
      compensation of motion and susceptibility artefacts. Blood suppression
      performance and its effect on temperature stability were evaluated in the
      ventricular septum of eight healthy volunteers using multislice double inversion
      recovery (MDIR), motion sensitized driven equilibrium (MSDE), and inflow
      saturation by saturation slabs (IS). It was shown that blood suppression during
      MR thermometry improves the contrast-to-noise ratio (CNR), the robustness of the
      applied motion correction algorithm as well as the temperature stability. A
      gradient echo sequence accelerated by an EPI readout and parallel imaging (SENSE)
      and using inflow saturation blood suppression was shown to achieve the best
      results. Temperature stabilities of 2  degrees C or better in the ventricular
      septum with a spatial resolution of 3.5 * 3.5 * 8mm(3) and a temporal resolution
      corresponding to the heart rate of the volunteer, were observed. Our results
      indicate that blood suppression improves the temperature stability when
      performing cardiac MR thermometry. The proposed MR thermometry protocol, which
      optimizes temperature stability in the ventricular septum, represents a step
      towards PRFS-based MR thermometry of the heart at 3 T.

PMID- 21732460
TI  - Prenatal diagnosis of a cleft of the tongue, lower lip and mandible.

PMID- 21732461
TI  - SonoAVC: a new tool in early diagnosis of patent urachus with bladder prolapse.

PMID- 21732462
TI  - Effect of image settings on nuchal translucency thickness measurement by a semi
      automated system.
AB  - OBJECTIVE: To investigate whether pre- and post-processing image settings affect
      NT measurements made by a semi-automatic method (SAM). METHODS: Different image
      settings (e.g. gain) were either adjusted one at a time on images that had been
      obtained during fetal NT scans (post-processing, n = 66), or adjusted one at a
      time during live scanning and image acquisition of the adult posterior tibial
      artery (pre-processing group, n = 91). The NT and luminal diameter of the
      posterior tibial artery, respectively, were measured by SAM on all original and
      adjusted images. RESULTS: Alteration of the image settings resulted in a
      statistically significant effect on the measurements taken by SAM, with an
      average pair difference ranging from 0.001 mm to 0.139 mm. Most of the
      differences were small and therefore the clinical impact would be negligible. The
      pair differences were greatest with a very high contrast setting, or without
      tissue harmonic imaging (THI); the paired difference in measurement in those with
      vs those without THI was more than 0.1 mm in over 40% of cases. CONCLUSIONS:
      Measurements made by SAM are affected by image settings.

PMID- 21732463
TI  - In vitro evaluation of hexagonal polymeric micelles in macrophage phagocytosis.
AB  - This paper develops a non-spherical polymeric micelle using an amphiphilic block
      copolymer and a porphyrin crystalline structure. The nanoscale polymer micelles
      were characterized by transmission electron microscopy (TEM) and atomic force
      microscopy (AFM), revealing particle sizes of approximately 150 nm with a
      particular shape in the hexagonal lattice. The shape shows the selective uptake
      efficacy for the HeLa and macrophage cells, and inhibits phagocytosis against the
      macrophage.

PMID- 21732464
TI  - Peripheral cyanohexyl substituent in wide bandgap polymer: increase the electron
      injection property for blue phosphorescence light emitting device.
AB  - Novel blue phosphor host, PCNCzSi, using 3,6-linked carbazole with delta-pi
      tetraphenylsilane segment as the main chain modified by peripheral cyanohexyl
      group was designed. The Si-carbazole backbone entitles the polymer with wide
      bandgap, high E(T) and good hole transporting ability. The introduction of
      peripheral CN group with high electron affinity enhances the electron injecting
      property of the polymer revealed by electron-only device and UPS measurement.
      Highly efficient spin-coated phosphorescent polymer light-emitting device, using
      PCNCzSi as the host for blue iridium complex, FIrpic, was realized. The maximum
      luminous efficiency and maximum external quantum efficiency of the device were 15
      cd/A and 6.7%, respectively, which are very high values for blue phosphorescent
      device using polymers as hosts as known.

PMID- 21732465
TI  - Thermal and Photochemical Control of Molecular Orientation of Azo-Functionalized
      Polymer Liquid Crystals and Application for Photo-Rewritable Paper.
AB  - A photo-responsive multi-bilayered film consisting of azobenzene polymer liquid
      crystals (PA6Az1) and poly(vinyl alcohol) (PVA) has been prepared on a glass
      substrate by alternate spin coating of the polymer solutions. The reflectivity of
      the multi-bilayered film disappears by annealing at 80  degrees C. The
      disappearance of the reflection by the annealing is related to the thermal out-of
      plane molecular orientation of PA6Az1 even in the multi-bilayered film, which
      leads to a very small difference in refractive indices between PA6Az1 and PVA.
      The reflectance of the multi-bilayered film is increased again by UV irradiation
      because of the transformation from the out-of-plane orientation to an in-plane
      random orientation. In this way, on-off switching of the reflection is achieved
      by combination of the thermally spontaneous out-of-plane molecular orientation
      and following photoisomerization of PA6Az1 comprising the multi-bilayered film. 

PMID- 21732466
TI  - Tuning the donor-acceptor strength of low-bandgap platinum-acetylide polymers for
      near-infrared photovoltaic applications.
AB  - Two near-infrared (NIR) absorbing metallopolyynes of platinum (P1 and P2)
      functionalized with a weakly electron-donating fluorene unit and two strong
      electron acceptors (viz. benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) and
      [1,2,5]thiadiazolo[3,4-i]dibenzo[a,c]phenazine) were synthesized and applied for
      NIR photovoltaic applications. With these designed weak donor-strong acceptor
      electronic traits, these metallopolymers possess narrow bandgaps of 1.54 and 1.65
      eV and a low HOMO level of about 5.50 eV, thus inducing a power conversion
      efficiency up to 1% for bulk heterojunction solar cells at the NIR wavelength.

PMID- 21732467
TI  - Self-healing in nanocomposite hydrogels.
AB  - Polymer hydrogels with characteristics distinct from those of solid materials are
      one of the most promising candidates for smart materials. Here, we report that a
      nanocomposite hydrogel (NC gel) consisting of a unique polymer/clay network
      structure, can exhibit complete self-healing through autonomic reconstruction of
      crosslinks across a damaged interface. Mechanical damage in NC gels can be
      repaired without the use of a healing agent, and even sections of NC gels
      separated by cutting, from whichever the same or different kinds of NC gel,
      perfectly (re-)combine by just contacting the cut surfaces together at mildly
      elevated temperatures. In NC gels, the autonomic fusion of cut surfaces as well
      as the self-healing could be achieved not only immediately after being cut but
      also after a long waiting time.

PMID- 21732468
TI  - Synthesis and characterizations of regioregular poly(3-alkylthiophene) with
      alternating dodecyl/1H,1H,2H,2H-perfluorooctyl side chains.
AB  - A regioregular poly[4'-dodecyl-3-(1H,1H,2H,2H-perfluorooctyl)-2,2'-bithiophene]
      (P3DDFT) with alternating alkyl and semifluoroalkyl side chains were synthesized.
      Short ethylene spacer between perfluorohexyl part and thiophene did not largely
      affect the absorption and emission properties of the polythiophene backbone in
      comparison with poly(3-dodecylthiophene) (P3DDT). P3DDFT showed a larger onset of
      the oxidation potential (+0.17 V) observed by cyclic voltamogram due to the
      electron withdrawing effect of the fluoroalkyl part. Thermal analysis and X-ray
      diffraction patterns indicated that P3DDFT in the solid state forms a
      semicrystalline lamellar structure that is similar to that of P3DDT. Ultraviolet
      photoemission spectroscopy was also used to investigate their electron structure
      in the films. Comparison of hole mobilities in the films suggested that P3DDFT
      could have a less ordered packing structure compared to P3DDT both in the bulk
      and at the dielectric interface.

PMID- 21732469
TI  - Oriented synthesis of one-dimensional polypyrrole molecule chains in a metal
      organic framework.
AB  - We report for the first time the preparation of single polypyrrole (PPy) molecule
      chains using a "metal-organic framework" with 1 nm channels as a template. The
      obtained one-dimensional (1-D) PPy has highly structure order and excellent
      conductivity, which has improved by as much as five orders of magnitude in
      comparison with that of 2-D PPy.

PMID- 21732470
TI  - One-pot synthesis of microcapsules with nanoscale inclusions.
AB  - Temperature responsive poly(N-isopropylmethacrylamide) (pNIPMAm) microgel
      capsules around 1 um containing multiple poly(N-isopropylacrylamide) (pNIPAm)
      nanoinclusions were prepared. This structure was achieved through the addition of
      a cross-linked pNIPMAm shell to stable, monodispersed aggregates of pNIPAm
      chains. This one-pot synthetic approach resulted in core/shell microgels at high
      temperature wherein only the shell (pNIPMAm) component contained stable, covalent
      cross-links between chains. Thus, upon decreasing the temperature following
      synthesis, the majority of the encapsulated pNIPAm chains escaped from the shell,
      resulting in nearly hollow microcapsules. Remnant pNIPAm segments in the
      microcapsule then form nanoparticulate inclusions upon raising the temperature.

PMID- 21732471
TI  - Circumpolar adaptation, social change, and the development of autoimmune thyroid
      disorders among the Yakut (Sakha) of Siberia.
AB  - OBJECTIVES: Alterations in thyroid function appear to play a central role in
      adaptation to Arctic environments. Increased thyroid activity in indigenous
      circumpolar populations is associated with upregulated metabolism, including
      elevated basal metabolic rate (BMR); however, little is known about the possible
      health consequences of these climate-induced changes on thyroid function. The
      focus of the present study is to determine the prevalence of autoimmune thyroid
      disorders and their lifestyle and metabolic correlates among a sample of
      indigenous Yakut adults from northeastern Siberia. METHODS: Anthropometric
      dimensions, health data, and plasma samples were collected among 281 adults (143
      women, 138 men; >=18 years old) from the rural community of Berdygestiakh (62
      degrees N, 127 degrees E; pop. 4,900), Sakha Republic (Yakutia), Russia. BMR
      measurements were available for 96 women and 98 men. Free triiodothyronine (T(3)
      ), free thyroxine (T(4) ), thyroid stimulating hormone (TSH), and anti-thyroid
      peroxidase antibody (TPOAb) levels were determined using enzyme immunoassay.
      RESULTS: Twenty-two percent of women and 6% of men had clinically elevated (>30
      IU/ml) TPOAb. TPOAb was positively correlated with TSH (P < 0.01), T(3) (P <
      0.05), and T(4) (P < 0.05) in women and showed a positive trend with T(4) (P =
      0.06) in men. Monthly household income was significantly positively correlated
      with TPOAb in men (P < 0.01) and showed a trend among women (P = 0.06).
      CONCLUSIONS: Although preliminary, these findings document higher than expected
      TPOAb levels among Yakut women and suggest possible consequences of increased
      thyroid activity associated with circumpolar adaptation and social change.

PMID- 21732472
TI  - A spatial view of the CD8+ T-cell response: the case of HCV.
AB  - In viral infections, a memory T-cell population comprises multiple subtypes of
      cells, distributed in diverse anatomic compartments and possibly re-circulating
      among them. Accordingly, memory T cells display distinct phenotypes and
      functions, depending on the nature of the infecting virus, the anatomic location
      of the infection, and the differences between the sites of active infection and T
      cell collection. This paper explores the body compartments where virus-specific
      CD8(+) T cells have been found during chronic hepatitis C virus infection,
      describes the cells' memory qualities, and discusses how they are spatially
      regulated, in comparison with other human viral infections. Understanding the
      role of compartmentalization and diversity of HCV-specific memory T-cell subsets
      may be the key to developing effective immunotherapies.

PMID- 21732473
TI  - Electronic database to detect drug-drug interactions between antidepressants and
      oral anticancer drugs from a cancer center in Singapore: implications to
      clinicians.
AB  - BACKGROUND: Electronic drug interaction databases are often utilized in clinical
      practice to detect for possible drug-drug interactions between drug pairs. It is
      uncertain, however, whether most of these detections interactions are clinically
      important in practice. To demonstrate these issues, this study utilized a
      comprehensive drug-drug interaction (DDI) electronic database to elucidate the
      prevalence of DDIs at a cancer centre between antidepressants and oral anticancer
      drugs (ACDs). METHODS: Drug utilization reports were retrieved to determine the
      patients who were prescribed with antidepressants oral ACDs between 2006 and 2009
      at a cancer center. Medication records of these patients were retrospectively
      examined using OncoRx, an internet-based oncology-specific database that allows
      the identification of DDIs. RESULTS: Out of 910 users of antidepressants, about
      one-third (281 patients, 30.9%) used an oral ACD and an antidepressant
      concomitantly. From these patients, about one-fifth (21.0%) had potential DDIs.
      These patients were users of 17 potentially interacting drug pairs. Ten out of
      the 17 drug pairs could potentially cause pharmacokinetic interactions, and the
      rest were pharmacodynamic interactions, with only three out of the 17 drug pairs
      were clinically documented to cause interacting events. CONCLUSION: The lack of
      screening conditions may have led to an over detection of DDI combinations by
      electronic DDI databases. Many of the detected interactions may not deem high
      significance in clinical practice. This study exposed a major weakness of current
      electronic DDI databases for detecting oral ACDs and antidepressants DDIs.

PMID- 21732474
TI  - Human induced pluripotent stem cells harbor homoplasmic and heteroplasmic
      mitochondrial DNA mutations while maintaining human embryonic stem cell-like
      metabolic reprogramming.
AB  - Human induced pluripotent stem cells (iPSCs) have been recently found to harbor
      genomic alterations. However, the integrity of mitochondrial DNA (mtDNA) within
      reprogrammed cells has yet to be investigated. mtDNA mutations occur at a high
      rate and contribute to the pathology of a number of human disorders. Furthermore,
      the lack of mtDNA integrity may alter cellular bioenergetics and limit efficient
      differentiation. We demonstrated previously that the derivation of iPSCs is
      associated with mitochondrial remodeling and a metabolic switch towards
      glycolysis. Here, we have discovered that alterations of mtDNA can occur upon the
      induction of pluripotency. Massively parallel pyrosequencing of mtDNA revealed
      that human iPSCs derived from young healthy donors harbored single base mtDNA
      mutations (substitutions, insertions, and deletions), both homoplasmic (in all
      mtDNA molecules) and heteroplasmic (in a fraction of mtDNAs), not present in the
      parental cells. mtDNA modifications were mostly common variants and not disease
      related. Moreover, iPSC lines bearing different mtDNA mutational loads maintained
      a consistent human embryonic stem cell-like reprogramming of energy metabolism.
      This involved the upregulation of glycolytic enzymes, increased glucose-6
      phosphate levels, and the over-expression of pyruvate dehydrogenase kinase 1
      protein, which reroutes the bioenergetic flux toward glycolysis. Hence, mtDNA
      mutations within iPSCs may not necessarily impair the correct establishment of
      pluripotency and the associated metabolic reprogramming. Nonetheless, the
      occurrence of pathogenic mtDNA modifications might be an important aspect to
      monitor when characterizing iPSC lines. Finally, we speculate that this random
      rearrangement of mtDNA molecules might prove beneficial for the derivation of
      mutation-free iPSCs from patients with mtDNA disorders.

PMID- 21732475
TI  - Concise review: Vascular stem cells and tumor angiogenesis.
AB  - Solid tumors are complex "organs" of cancer cells and a heterogeneous population
      of hematopoietic cells, mesenchymal cells, and endothelial cells. The cancer stem
      cell model proposes that tumor growth and progression is driven by rare
      populations of cancer stem cells; however, nontumor-forming stem and progenitor
      cells are also present within the tumor microenvironment. These adult stem cells
      do not form tumors when injected into experimental animals, but they may augment
      tumor growth through juxtacrine and paracrine regulation of tumor cells and by
      contributing to neovascularization. Thus, cancer cells may actively co-opt
      nontumor-forming stem cells distally from the bone marrow or proximally from
      nearby tissue and subvert their abilities to differentiate and maintain tissue
      growth, repair, and angiogenesis. This review will cover the roles of nontumor
      forming vascular stem cells in tumor growth and angiogenesis.

PMID- 21732476
TI  - Concise review: Bone marrow for the treatment of spinal cord injury: mechanisms
      and clinical applications.
AB  - Transplantation of bone marrow stem cells into spinal cord lesions enhances
      axonal regeneration and promotes functional recovery in animal studies. There are
      two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and
      mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might
      promote spinal cord repair following transplantation have been extensively
      investigated. The objective of this review is to discuss these mechanisms; we
      briefly consider the controversial topic of HSC and MSC transdifferentiation into
      central nervous system cells but focus on the neurotrophic, tissue sparing, and
      reparative action of MSC grafts in the context of the spinal cord injury (SCI)
      milieu. We then discuss some of the specific issues related to the translation of
      HSC and MSC therapies for patients with SCI and present a comprehensive critique
      of the current bone marrow cell clinical trials for the treatment of SCI to date.

PMID- 21732477
TI  - FUS-CHOP fusion protein expression coupled to p53 deficiency induces liposarcoma
      in mouse but not in human adipose-derived mesenchymal stem/stromal cells.
AB  - Human sarcomas have been modeled in mice by expression of specific fusion genes
      in mesenchymal stem cells (MSCs). However, sarcoma models based on human MSCs are
      still missing. We attempted to develop a model of liposarcoma by expressing FUS
      (FUsed in Sarcoma; also termed TLS, Translocated in LipoSarcoma)-CHOP (C/EBP
      HOmologous Protein; also termed DDIT3, DNA Damage-Inducible Transcript 3), a
      hallmark mixoid liposarcoma-associated fusion oncogene, in wild-type and p53
      deficient mouse and human adipose-derived mesenchymal stem/stromal cells (ASCs).
      FUS-CHOP induced liposarcoma-like tumors when expressed in p53(-/-) but not in
      wild-type (wt) mouse ASCs (mASCs). In the absence of FUS-CHOP, p53(-/-) mASCs
      forms leiomyosarcoma, indicating that the expression of FUS-CHOP redirects the
      tumor genesis/phenotype. FUS-CHOP expression in wt mASCs does not initiate
      sarcomagenesis, indicating that p53 deficiency is required to induce FUS-CHOP
      mediated liposarcoma in fat-derived mASCs. In a human setting, p53-deficient
      human ASCs (hASCs) displayed a higher in vitro growth rate and a more extended
      lifespan than wt hASCs. However, FUS-CHOP expression did not induce further
      changes in culture homeostasis nor initiated liposarcoma in either wt or p53
      depleted hASCs. These results indicate that FUS-CHOP expression in a p53
      deficient background is sufficient to initiate liposarcoma in mouse but not in
      hASCs, suggesting the need of additional cooperating mutations in hASCs. A
      microarray gene expression profiling has shed light into the potential
      deregulated pathways in liposarcoma formation from p53-deficient mASCs expressing
      FUS-CHOP, which might also function as potential cooperating mutations in the
      transformation process from hASCs.

PMID- 21732478
TI  - The apical polarity determinant Crumbs 2 is a novel regulator of ESC-derived
      neural progenitors.
AB  - ESCs undergoing neural differentiation in vitro display an intrinsic
      heterogeneity with a large subset of the cells forming polarized neural rosettes
      that maintain the neural progenitor microenvironment. This heterogeneity is not
      only necessary for normal development but also causes substantial technical
      challenges for practical applications. Here, we report a novel regulator of early
      neural progenitors, the apical polarity protein Crb2 (Crumbs homologue 2).
      Employing monolayer differentiation of mouse ESCs to model neurogenesis in vitro,
      we find that Crb2 is upregulated with Sox1 and Musashi at the onset of
      neuroepithelial specification and localizes to the apical side of neural
      rosettes. Stable Crb2-knockdown (KD) lines die at the onset of neural
      specification and fail to stabilize several apical polarity proteins. However,
      these cells are able to proliferate under self-renewing conditions and can be
      differentiated into mesodermal and endodermal lineages. Conversely, Crb2
      overexpression during neural differentiation results in elevated levels of other
      apical polarity proteins and increases proliferation. Additionally, sustained
      overexpression of Crb2 reduces terminal differentiation into TuJ1-positive
      neurons. Furthermore, we demonstrate that Crb2 overexpression under self-renewing
      conditions increases glycogen synthase kinase (GSK)-3beta inhibition, correlating
      with an increase in clonogenicity. To confirm the importance of GSK-3beta
      inhibition downstream of Crb2, we show that Crb2-KD cells can be forced into
      neural lineages by blocking GSK-3beta function and supplementing Epidermal Growth
      Factor (EGF) and basic Fibroblast Growth Factor (bFGF). Thus, this is the first
      demonstration that a member of the Crumbs family is essential for survival and
      differentiation of ESC-derived neural progenitors.

PMID- 21732479
TI  - Osteoblasts derived from induced pluripotent stem cells form calcified structures
      in scaffolds both in vitro and in vivo.
AB  - Reprogramming somatic cells into an ESC-like state, or induced pluripotent stem
      (iPS) cells, has emerged as a promising new venue for customized cell therapies.
      In this study, we performed directed differentiation to assess the ability of
      murine iPS cells to differentiate into bone, cartilage, and fat in vitro and to
      maintain an osteoblast phenotype on a scaffold in vitro and in vivo. Embryoid
      bodies derived from murine iPS cells were cultured in differentiation medium for
      8-12 weeks. Differentiation was assessed by lineage-specific morphology, gene
      expression, histological stain, and immunostaining to detect matrix deposition.
      After 12 weeks of expansion, iPS-derived osteoblasts were seeded in a gelfoam
      matrix followed by subcutaneous implantation in syngenic imprinting control
      region (ICR) mice. Implants were harvested at 12 weeks, histological analyses of
      cell and mineral and matrix content were performed. Differentiation of iPS cells
      into mesenchymal lineages of bone, cartilage, and fat was confirmed by morphology
      and expression of lineage-specific genes. Isolated implants of iPS cell-derived
      osteoblasts expressed matrices characteristic of bone, including osteocalcin and
      bone sialoprotein. Implants were also stained with alizarin red and von Kossa,
      demonstrating mineralization and persistence of an osteoblast phenotype.
      Recruitment of vasculature and microvascularization of the implant was also
      detected. Taken together, these data demonstrate functional osteoblast
      differentiation from iPS cells both in vitro and in vivo and reveal a source of
      cells, which merit evaluation for their potential uses in orthopedic medicine and
      understanding of molecular mechanisms of orthopedic disease.

PMID- 21732480
TI  - An endothelial cell niche induces hepatic specification through dual repression
      of Wnt and Notch signaling.
AB  - Complex cross-talk between endoderm and the microenvironment is an absolute
      requirement to orchestrate hepatic specification and expansion. In the mouse, the
      septum transversum and cardiac mesoderm, through secreted bone morphogenetic
      proteins (BMP) and fibroblast growth factors (FGF), respectively, instruct the
      adjacent ventral endoderm to become hepatic endoderm. Consecutively, endothelial
      cells promote expansion of the specified hepatic endoderm. By using a mouse
      reporter embryonic stem cell line, in which hCD4 and hCD25 were targeted to the
      Foxa2 and Foxa3 loci, we reconstituted an in vitro culture system in which
      committed endoderm cells coexpressing hCD4-Foxa2 and hCD25-Foxa3 were isolated
      and cocultured with endothelial cells in the presence of BMP4 and bFGF. In this
      culture setting, we provide mechanistic evidence that endothelial cells function
      not only to promote hepatic endoderm expansion but are also required at an
      earlier step for hepatic specification, at least in part through regulation of
      the Wnt and Notch pathways. Activation of Wnt and Notch by chemical or genetic
      approaches increases endoderm cell numbers but inhibits hepatic specification,
      and conversely, chemical inhibition of both pathways enhances hepatic
      specification and reduces proliferation. By using identical coculture conditions,
      we defined a similar dependence of endoderm harvested from embryos on endothelial
      cells to support their growth and hepatic specification. Our findings (1) confirm
      a conserved role of Wnt repression for mouse hepatic specification, (2) uncover a
      novel role for Notch repression in the hepatic fate decision, and (3) demonstrate
      that repression of Wnt and Notch signaling in hepatic endoderm is controlled by
      the endothelial cell niche.

PMID- 21732481
TI  - PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell
      pluripotency and somatic cell reprogramming.
AB  - Polycomb repressive complex two (PRC2) has been implicated in embryonic stem (ES)
      cell pluripotency; however, the mechanistic roles of this complex are unclear. It
      was assumed that ES cells contain PRC2 with the same subunit composition as that
      identified in HeLa cells and Drosophila embryos. Here, we report that PRC2 in
      mouse ES cells contains at least three additional subunits: JARID2, MTF2, and a
      novel protein denoted esPRC2p48. JARID2, MTF2, and esPRC2p48 are highly expressed
      in mouse ES cells compared to differentiated cells. Importantly, knockdowns of
      JARID2, MTF2, or esPRC2p48 alter the level of PRC2-mediated H3K27 methylation and
      result in the expression of differentiation-associated genes in ES cells.
      Interestingly, expression of JARID2, MTF2, and esPRC2p48 together, but not
      individually, enhances Oct4/Sox2/Klf4-mediated reprogramming of mouse embryonic
      fibroblasts (MEFs) into induced pluripotent stem cells, whereas knockdown or
      knockout of JARID2, MTF2, or esPRC2p48 significantly inhibits reprogramming.
      JARID2, MTF2, and esPRC2p48 modulate H3K27 methylation and facilitate repression
      of lineage-associated gene expression when transduced into MEFs, and
      synergistically stimulate the histone methyltransferase activity of PRC2 in
      vitro. Therefore, these studies identify JARID2, MTF2, and esPRC2p48 as important
      regulatory subunits of PRC2 in ES cells and reveal critical functions of these
      subunits in modulating PRC2's activity and gene expression both in ES cells and
      during somatic cell reprogramming.

PMID- 21732482
TI  - A nonhuman primate model for urinary bladder regeneration using autologous
      sources of bone marrow-derived mesenchymal stem cells.
AB  - Animal models that have been used to examine the regenerative capacity of cell
      seeded scaffolds in a urinary bladder augmentation model have ultimately
      translated poorly in the clinical setting. This may be due to a number of factors
      including cell types used for regeneration and anatomical/physiological
      differences between lower primate species and their human counterparts. We
      postulated that mesenchymal stem cells (MSCs) could provide a cell source for
      partial bladder regeneration in a newly described nonhuman primate bladder
      (baboon) augmentation model. Cell-sorted CD105(+) /CD73(+) /CD34(-) /CD45(-)
      baboon MSCs transduced with green fluorescent protein (GFP) were seeded onto
      small intestinal submucosa (SIS) scaffolds. Baboons underwent an approximate 40%
      50% cystectomy followed by augmentation cystoplasty with the aforementioned
      scaffolds or controls and finally enveloped with omentum. Bladders from sham,
      unseeded SIS, and MSC/SIS scaffolds were subjected to trichrome, H&E, and
      immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining
      for muscle markers combined with an anti-GFP antibody revealed that >90% of the
      cells were GFP(+) /muscle marker(+) and >70% were GFP(+) /Ki-67(+) demonstrating
      grafted cells were present and actively proliferating within the grafted region.
      Trichrome staining of MSC/SIS-augmented bladders exhibited typical bladder
      architecture and quantitative morphometry analyses revealed an approximate 32%
      and 52% muscle to collagen ratio in unseeded versus seeded animals, respectively.
      H&E staining revealed a lack of infiltration of inflammatory cells in grafted
      animals and in corresponding kidneys and ureters. Simple cystometry indicated
      recovery between 28% and 40% of native bladder capacity. Data demonstrate MSC/SIS
      composites support regeneration of bladder tissue and validate this new bladder
      augmentation model.

PMID- 21732483
TI  - Enrichment of human ESC-derived multipotent mesenchymal stem cells with
      immunosuppressive and anti-inflammatory properties capable to protect against
      experimental inflammatory bowel disease.
AB  - Human ESCs provide access to the earliest stages of human development and may
      serve as an unlimited source of functional cells for future cell therapies. The
      optimization of methods directing the differentiation of human embryonic stem
      cells (hESCs) into tissue-specific precursors becomes crucial. We report an
      efficient enrichment of mesenchymal stem cells (MSCs) from hESCs through specific
      inhibition of SMAD-2/3 signaling. Human ESC-derived MSCs (hESC-MSCs) emerged as a
      population of fibroblastoid cells expressing a MSC phenotype: CD73+ CD90+ CD105+
      CD44+ CD166+ CD45- CD34- CD14- CD19- human leucocyte antigen-DR (HLA-DR)-. After
      28 days of SMAD-2/3 inhibition, hESC cultures were enriched (>42%) in multipotent
      MSCs. CD73+CD90+ hESC-MSCs were fluorescence activated cell sorting (FACS)
      isolated and long-term cultures were established and maintained for many passages
      displaying a faster growth than somatic tissue-derived MSCs while maintaining MSC
      morphology and phenotype. They displayed osteogenic, adipogenic, and chondrocytic
      differentiation potential and exhibited potent immunosuppressive and anti
      inflammatory properties in vitro and in vivo, where hESC-MSCs were capable of
      protecting against an experimental model of inflammatory bowel disease.
      Interestingly, the efficient enrichment of hESCs into MSCs through inhibition of
      SMAD-2/3 signaling was not reproducible with distinct induced pluripotent stem
      cell lines. Our findings provide mechanistic insights into the differentiation of
      hESCs into immunosuppressive and anti-inflammatory multipotent MSCs with
      potential future clinical applications.

PMID- 21732484
TI  - Human placenta-derived adherent cells prevent bone loss, stimulate bone
      formation, and suppress growth of multiple myeloma in bone.
AB  - Human placenta has emerged as a valuable source of transplantable cells of
      mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes,
      including enhanced engraftment of hematopoietic stem cells, modulation of
      inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs)
      are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple
      myeloma is closely associated with induction of bone disease and large lytic
      lesions, which are often not repaired and are usually the sites of relapses. We
      evaluated the antimyeloma therapeutic potential, in vivo survival, and
      trafficking of PDACs in the severe combined immunodeficiency (SCID)-rab model of
      medullary myeloma-associated bone loss. Intrabone injection of PDACs into
      nonmyelomatous and myelomatous implanted bone in SCID-rab mice promoted bone
      formation by stimulating endogenous osteoblastogenesis, and most PDACs
      disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone
      disease and tumor growth were dose-dependent and comparable with those of fetal
      human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment
      of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor
      injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small
      number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma
      cell growth rate in vitro was lower in coculture with PDACs than with MSCs from
      human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast
      precursors and inhibited their differentiation. This study suggests that altering
      the bone marrow microenvironment with PDAC cytotherapy attenuates growth of
      myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma
      osteolysis.

PMID- 21732485
TI  - Transplanted stem cell-secreted vascular endothelial growth factor effects
      poststroke recovery, inflammation, and vascular repair.
AB  - Cell transplantation offers a novel therapeutic strategy for stroke; however, how
      transplanted cells function in vivo is poorly understood. We show for the first
      time that after subacute transplantation into the ischemic brain of human central
      nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell
      secreted factor, human vascular endothelial growth factor (hVEGF), is necessary
      for cell-induced functional recovery. We correlate this functional recovery to
      hVEGF-induced effects on the host brain including multiple facets of vascular
      repair and its unexpected suppression of the inflammatory response. We found that
      transplanted hCNS-SCns affected multiple parameters in the brain with different
      kinetics: early improvement in blood-brain barrier integrity and suppression of
      inflammation was followed by a delayed spatiotemporal regulated increase in
      neovascularization. These events coincided with a bimodal pattern of functional
      recovery, with, an early recovery independent of neovascularization, and a
      delayed hVEGF-dependent recovery coincident with neovascularization. Therefore,
      cell transplantation therapy offers an exciting multimodal strategy for brain
      repair in stroke and potentially other disorders with a vascular or inflammatory
      component.

PMID- 21732486
TI  - Locally applied vascular endothelial growth factor A increases the osteogenic
      healing capacity of human adipose-derived stem cells by promoting osteogenic and
      endothelial differentiation.
AB  - Human adipose-derived stem cells (hASCs) are known for their capability to
      promote bone healing when applied to bone defects. For bone tissue regeneration,
      both sufficient angiogenesis and osteogenesis is desirable. Vascular endothelial
      growth factor A (VEGFA) has the potential to promote differentiation of common
      progenitor cells to both lineages. To test this hypothesis, the effects of VEGFA
      on hASCs during osteogenic differentiation were tested in vitro. In addition,
      hASCs were seeded in murine critical-sized calvarial defects locally treated with
      VEGFA. Our results suggest that VEGFA improves osteogenic differentiation in
      vitro as indicated by alkaline phosphatase activity, alizarin red staining, and
      quantitative real-time polymerase chain reaction analysis. Moreover, local
      application of VEGFA to hASCs significantly improved healing of critical-sized
      calvarial defects in vivo. This repair was accompanied by a striking enhancement
      of angiogenesis. Both paracrine and, to a lesser degree, cell-autonomous effects
      of VEGFA-treated hASCs were accountable for angiogenesis. These data were
      confirmed by using CD31(-) /CD45(-) mouse ASCs(GFP+) cells. In summary, we
      demonstrated that VEGFA increased osteogenic differentiation of hASCS in vitro
      and in vivo, which was accompanied by an enhancement of angiogenesis.
      Additionally, we showed that during bone regeneration, the increase in
      angiogenesis of hASCs on treatment with VEGFA was attributable to both paracrine
      and cell-autonomous effects. Thus, locally applied VEGFA might prove to be a
      valuable growth factor that can mediate both osteogenesis and angiogenesis of
      multipotent hASCs in the context of bone regeneration.

PMID- 21732487
TI  - PKCdelta-induced PU.1 phosphorylation promotes hematopoietic stem cell
      differentiation to dendritic cells.
AB  - Human CD34(+) hematopoietic stem cells (HSCs) exhibit the potential to
      differentiate into a variety of specialized blood cells. The distinct
      intracellular mechanisms that control cell fate and lineage commitment of these
      multipotent cells are not well defined. In this study, we investigate and
      modulate the signaling processes during HSC differentiation toward myeloid
      dendritic cells (mDCs). DC differentiation induced by the cytokines Granulocyte
      macrophage colony-stimulating factor (GM-CSF) and Interleukin-4 (IL-4) led to
      activation of the Extracellular-signal-regulated kinase (ERK), protein kinase C
      (PKC), and Janus kinase (JAK)/Signal Transducer and Activator of Transcription
      (STAT) but not the SAPK/c-Jun NH(2) -terminal kinase and p38 mitogen-activated
      protein kinase signaling pathways. From the activated signaling pathways the PKC
      isoform delta was found to phosphorylate the transcription factor PU.1, which is
      described as one of the key factors for myeloid HSC differentiation. On molecular
      level, PKCdelta regulated PU.1 activity by affecting its transactivation
      activity, whereas its DNA binding activity remained unaffected. This was
      accompanied by PKCdelta-induced phosphorylation of the PU.1 transactivation
      domain. Furthermore, treatment with PKC- and ERK1/2-specific signaling inhibitors
      impaired both HSC differentiation toward mDCs as well as phosphorylation-mediated
      transactivation activity of PU.1. Taken together, these results provide new
      insights into the molecular mechanisms promoting the differentiation process of
      HSCs toward mDCs and introduce the PKC isoform delta as critical mediator.

PMID- 21732488
TI  - GABAA receptor signaling induces osmotic swelling and cell cycle activation of
      neonatal prominin+ precursors.
AB  - Signal-regulated changes in cell size affect cell division and survival and
      therefore are central to tissue morphogenesis and homeostasis. In this respect,
      GABA receptors (GABA(A)Rs) are of particular interest because allowing anions
      flow across the cell membrane modulates the osmolyte flux and the cell volume.
      Therefore, we have here investigated the hypothesis that GABA may regulate neural
      stem cell proliferation by inducing cell size changes. We found that, besides
      neuroblasts, also neural precursors in the neonatal murine subependymal zone
      sense GABA via GABA(A) Rs. However, unlike in neuroblasts, where it induced
      depolarization-mediated [Ca(2+)](i) increase, GABA(A) Rs activation in precursors
      caused hyperpolarization. This resulted in osmotic swelling and increased surface
      expression of epidermal growth factor receptors (EGFRs). Furthermore, activation
      of GABA(A) Rs signaling in vitro in the presence of EGF modified the expression
      of the cell cycle regulators, phosphatase and tensin homolog and cyclin D1,
      increasing the pool of cycling precursors without modifying cell cycle length. A
      similar effect was observed on treatment with diazepam. We also demonstrate that
      GABA and diazepam responsive precursors represent prominin(+) stem cells.
      Finally, we show that as in in vitro also in in vivo a short administration of
      diazepam promotes EGFR expression in prominin(+) stem cells causing activation
      and cell cycle entry. Thus, our data indicate that endogenous GABA is a part of a
      regulatory mechanism of size and cell cycle entry of neonatal stem cells. Our
      results also have potential implications for the therapeutic practices that
      involve exposure to GABA(A) Rs modulators during neurodevelopment.

PMID- 21732489
TI  - Sur8/Shoc2 involves both inhibition of differentiation and maintenance of self
      renewal of neural progenitor cells via modulation of extracellular signal
      regulated kinase signaling.
AB  - Sur8/Shoc2 is a scaffold protein that regulates the Ras-extracellular signal
      regulated kinase (ERK) pathway. However, the roles of Sur8 in cellular
      physiologies are poorly understood. In this study, Sur8 was severely repressed in
      the course of neural progenitor cell (NPC) differentiation in the cerebral cortex
      of developing rat embryos. Similarly, Sur8 was also critically reduced in
      cultured NPCs, which were induced differentiation by removal of basic fibroblast
      growth factor (bFGF). Sur8 regulation occurs at the protein level rather than at
      the mRNA level as revealed by both in situ hybridization and reverse
      transcriptase polymerase chain reaction analyses. The role of Sur8 in NPC
      differentiation was confirmed by lentivirus-mediated Sur8 knockdown, which
      resulted in increased differentiation, whereas exogenous expression of Sur8
      inhibited differentiation. Contrastingly, NPC proliferation was promoted by
      overexpression, but was suppressed by Sur8 knockdown. The role of Sur8 as an
      antidifferentiation factor in the developing rat brain was confirmed by an ex
      vivo embryo culture system combined with the lentivirus-mediated Sur8 knockdown.
      The numbers and sizes of neurospheres were reduced, but neuronal outgrowth was
      enhanced by the Sur8 knockdown. The Ras-ERK pathway is involved in Sur8-mediated
      regulations of differentiation, as the treatment of ERK kinase (MEK) inhibitors
      blocks the effects of Sur8. The regulations of NPCs' differentiation and
      proliferation by the Ras-ERK pathway were also shown by the rescues of the
      effects of bFGF depletion, neuronal differentiation, and antiproliferation by
      epidermal growth factor. In summary, Sur8 is an antidifferentiation factor that
      stimulates proliferation for maintenance of self-renewal in NPCs via modulation
      of the Ras-ERK pathway.

PMID- 21732490
TI  - The Rho kinase pathway regulates mouse adult neural precursor cell migration.
AB  - Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally
      migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB).
      Following neural injury, they also migrate to the site of damage. This study
      investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in
      vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of
      ROCK using Y27632 promoted cell body elongation, process protrusion, and
      migration, while inhibiting NPC chain formation. It had no effect on
      proliferation, apoptosis, or differentiation. Both isoforms of ROCK were
      involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote
      NPC migration and morphological changes; knockdown of ROCK2 alone was partially
      effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion
      of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week
      reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion
      alone. However, ROCK inhibition did not affect the tangential-to-radial switch of
      NPC migration, as labeled cells were present in all OB layers. The decrease in
      NPC number at the OB was not attributed to a decrease in NPCs at the SVZ.
      However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS
      and increased the distribution of these cells to ectopic brain regions, such as
      the accessory olfactory nucleus, where the majority differentiated into neurons.
      These findings suggest that ROCK signaling regulates NPC migration via regulation
      of cell-cell contact and chain migration.

PMID- 21732491
TI  - Adult human Muller glia cells are a highly efficient source of rod
      photoreceptors.
AB  - There is growing evidence that Muller glia cells (MGCs) might act as regenerative
      elements in injured retinas of fishes and amniotes. However, their
      differentiation potential in humans is yet unknown. We isolated Muller glia from
      adult human retinas and propagated them in vitro revealing for the first time
      their ability to differentiate into rod photoreceptors. These results were also
      confirmed with mice retinas. Here, we describe conditions by which human MGCs
      adopt a rod photoreceptor commitment with a surprising efficiency as high as 54%.
      Functional characterization of Muller glia-derived photoreceptors by patch-clamp
      recordings revealed that their electrical properties are comparable to those of
      adult rods. Interestingly, our procedure allowed efficient derivation of MGC
      cultures starting from both injured and degenerating and postmortem human
      retinas. Human transplanted Muller glia-derived photoreceptors integrate and
      survive within immunodeficient mouse retinas. These data provide evidence that
      Muller glia retains an unpredicted plasticity and multipotent potential into
      adulthood, and it is therefore a promising source of novel therapeutic
      applications in retinal repair.

PMID- 21732492
TI  - Pretreatment of human mesenchymal stem cells with pioglitazone improved
      efficiency of cardiomyogenic transdifferentiation and cardiac function.
AB  - The efficacy of transplantation of default human marrow-derived mesenchymal stem
      cells (MSCs) was modest. In this study, our challenge was to improve the efficacy
      of MSC transplantation in vivo by pretreatment of MSCs with pioglitazone. MSCs
      were cultured with or without medium containing 1 MUM of pioglitazone before
      cardiomyogenic induction. After cardiomyogenic induction in vitro, cardiomyogenic
      transdifferentiation efficiency (CTE) was calculated by immunocytochemistry using
      anti-cardiac troponin-I antibody. For the in vivo experiments, myocardial
      infarction (MI) at the anterior left ventricle was made in nude rats. Two weeks
      after MI, MSCs pretreated with pioglitazone (p-BM; n = 30) or without
      pioglitazone (BM; n = 17) were injected, and then survived for 2 weeks. We
      compared left ventricular function by echocardiogram and immunohistochemistry to
      observe cardiomyogenic transdifferentiation in vivo. Pretreatment with
      pioglitazone significantly increased the CTE in vitro (1.9% +/- 0.2% n = 47 vs.
      39.5% +/- 4.7% n = 13, p < .05). Transplantation of pioglitazone pretreated MSCs
      significantly improved change in left ventricular % fractional shortening (BM; 
      4.8% +/- 2.1%, vs. p-BM; 5.2% +/- 1.5%). Immunohistochemistry revealed
      significant improvement of cardiomyogenic transdifferentiation in p-BM in vivo
      (BM; 0% +/- 0% n = 5, vs. p-BM; 0.077% +/- 0.041% n = 5). Transplantation of
      pioglitazone-pretreated MSCs significantly improved cardiac function and can be a
      promising cardiac stem cell source to expect cardiomyogenesis.

PMID- 21732493
TI  - A fibrin patch-based enhanced delivery of human embryonic stem cell-derived
      vascular cell transplantation in a porcine model of postinfarction left
      ventricular remodeling.
AB  - It is unknown how to use human embryonic stem cell (hESC) to effectively treat
      hearts with postinfarction left ventricular (LV) remodeling. Using a porcine
      model of postinfarction LV remodeling, this study examined the functional
      improvement of enhanced delivery of combined transplantation of hESC-derived
      endothelial cells (ECs) and hESC-derived smooth muscle cells (SMCs) with a fibrin
      three-dimensional (3D) porous scaffold biomatrix. To facilitate tracking the
      transplanted cells, the hESCs were genetically modified to stably express green
      fluorescent protein and luciferase (GFP/Luc). Myocardial infarction (MI) was
      created by ligating the first diagonal coronary artery for 60 minutes followed by
      reperfusion. Two million each of GFP/Luc hESC-derived ECs and SMCs were seeded in
      the 3D porous biomatrix patch and applied to the region of ischemia/reperfusion
      for cell group (MI+P+C, n = 6), whereas biomatrix without cell (MI+P, n = 5), or
      saline only (MI, n = 5) were applied to control group hearts with same coronary
      artery ligation. Functional outcome (1 and 4 weeks follow-up) of stem cell
      transplantation was assessed by cardiac magnetic resonance imaging. The
      transplantation of hESC-derived vascular cells resulted in significant LV
      functional improvement. Significant engraftment of hESC-derived cells was
      confirmed by both in vivo and ex vivo bioluminescent imaging. The mechanism
      underlying the functional beneficial effects of cardiac progenitor
      transplantation is attributed to the increased neovascularization. These findings
      demonstrate a promising therapeutic potential of using these hESC-derived
      vascular cell types and the mode of patch delivery.

PMID- 21732494
TI  - Growth factor independence 1 protects hematopoietic stem cells against apoptosis
      but also prevents the development of a myeloproliferative-like disease.
AB  - The regulation of gene transcription is elementary for the function of
      hematopoietic stem cells (HSCs). The transcriptional repressor growth factor
      independence 1 (Gfi1) restricts HSC proliferation and is essential to maintain
      their self-renewal capacity and multipotency after transplantation. In addition,
      Gfi1(-/-) HSCs are severely compromised in their ability to compete with wild
      type (wt) HSCs after transplantation. We now report that Gfi1 protects HSCs
      against stress-induced apoptosis, probably, by repressing the proapoptotic target
      gene Bax, since irradiated Gfi1(-/-) HSCs display higher expression of Bax and
      show a higher rate of apoptosis than wt HSCs. This protective function of Gfi1
      appears to be functionally relevant since Gfi1(-/-) HSCs that express Bcl-2,
      which antagonizes the effects of Bax, regain their ability to self renew and to
      initiate multilineage differentiation after transplantation. Surprisingly, Gfi1(
      /-) xBcl-2 transgenic mice also show a strong, systemic expansion of Mac-1(+) Gr
      1(-) myeloid cells in bone marrow and peripheral lymphoid organs. These cells
      express high levels of the proleukemogenic transcription factor Hoxa9 and, in
      older mice, appear as atypical monocytoid-blastoid cells in the peripheral blood.
      As a result of this massive expansion of myeloid cells, all Gfi1(-/-) xBcl-2 mice
      eventually succumb to a myeloproliferative-like disease resembling a preleukemic
      state. In summary, our data demonstrate that Gfi1's ability to protect against
      apoptosis is essential for HSC function. In addition, our finding show that Gfi1
      prevents the development of myeloproliferative diseases and provides evidence how
      Gfi1 deficiency could be linked to myeloid leukemia.

PMID- 21732495
TI  - Radical acceleration of nuclear reprogramming by chromatin remodeling with the
      transactivation domain of MyoD.
AB  - Induced pluripotent stem cells (iPSCs) can be created by reprogramming
      differentiated cells through introduction of defined genes, most commonly Oct4,
      Sox2, Klf4, and c-Myc (OSKM). However, this process is slow and extremely
      inefficient. Here, we demonstrate radical acceleration of iPSC creation with a
      fusion gene between Oct4 and the powerful transactivation domain (TAD) of MyoD
      (M(3)O). Transduction of M(3) O as well as Sox2, Klf4, and c-Myc into fibroblasts
      effectively remodeled patterns of DNA methylation, chromatin accessibility,
      histone modifications, and protein binding at pluripotency genes, raising the
      efficiency of making mouse and human iPSCs more than 50-fold in comparison to
      OSKM. These results identified that one of the most critical barriers to iPSC
      creation is poor chromatin accessibility and protein recruitment to pluripotency
      genes. The MyoD TAD has a capability of overcoming this problem. Our approach of
      fusing TADs to unrelated transcription factors has far-reaching implications as a
      powerful tool for transcriptional reprogramming beyond application to iPSC
      technology.

PMID- 21732496
TI  - Crucial role of c-Myc in the generation of induced pluripotent stem cells.
AB  - c-Myc transduction has been considered previously to be nonessential for induced
      pluripotent stem cell (iPSC) generation. In this study, we investigated the
      effects of c-Myc transduction on the generation of iPSCs from an inbred mouse
      strain using a genome integration-free vector to exclude the effects of the
      genetic background and the genomic integration of exogenous genes. Our findings
      reveal a clear difference between iPSCs generated using the four defined factors
      including c-Myc (4F-iPSCs) and those produced without c-Myc (3F-iPSCs). Molecular
      and cellular analyses did not reveal any differences between 3F-iPSCs and 4F
      iPSCs, as reported previously. However, a chimeric mice formation test indicated
      clear differences, whereby few highly chimeric mice and no germline transmission
      was observed using 3F-iPSCs. Similar differences were also observed in the mouse
      line that has been widely used in iPSC studies. Furthermore, the defect in 3F
      iPSCs was considerably improved by trichostatin A, a histone deacetyl transferase
      inhibitor, indicating that c-Myc plays a crucial role in iPSC generation through
      the control of histone acetylation. Indeed, low levels of histone acetylation
      were observed in 3F-iPSCs. Our results shed new light on iPSC generation
      mechanisms and strongly recommend c-Myc transduction for preparing high-quality
      iPSCs.

PMID- 21732497
TI  - Neural stem cells maintain their stemness through protein kinase C zeta-mediated
      inhibition of TRIM32.
AB  - Several studies over the last couple of years have delivered insights into the
      mechanisms that drive neuronal differentiation. However, the mechanisms that
      ensure the maintenance of stemness characteristics in neural stem cells over
      several rounds of cell divisions are still largely unknown. Here, we provide
      evidence that the neuronal fate determinant TRIM32 binds to the protein kinase C
      zeta. Through this interaction, TRIM32 is retained in the cytoplasm. However,
      during differentiation, this interaction is abrogated and TRIM32 translocates to
      the nucleus to initiate neuronal differentiation by targeting c-Myc for
      proteasomal degradation.

PMID- 21732498
TI  - Control design and implementation of a novel master-slave surgery robot system,
      MicroHand A.
AB  - BACKGROUND: Compared with conventional minimally invasive surgery and open
      surgery, robotic-assisted minimally invasive surgery can overcome or eliminate
      drawbacks caused by operator restrictions, motion limitation by the trocar and
      the image system, such as fatigue, trembling, low precision, constrained degree
      of-freedom, poor hand-eye coordination and restricted surgical vision. In this
      paper, a novel partly tendon-driven master-slave robot system is proposed to
      assist minimally invasive surgery and a master-slave control architecture is
      developed for abdominal surgical operations. METHODS: A novel master-slave
      surgery robot system named MicroHand A has been developed. A kinematic analysis
      of master and slave manipulators was conducted, based on screw theory and vector
      loop equation. The relationships of the tendon-driven multi-DOF surgical
      instrument among Cartesian space, actuator space and joint space were derived for
      control purposes. The control system architecture of the MicroHand A was designed
      with intuitive motion control and motion scaling control. Llewellyn's absolute
      stability criterion and the transparency of the one-DOF master-slave system are
      also analysed. RESULTS: Intuitive motion control under dissimilar kinematics in
      master-slave manipulations and motion scaling control were accomplished to solve
      absonant hand-eye coordination, kinematic dissimilarity and workspace mismatch of
      master-slave manipulator problems. A series of tests and animal experiments were
      carried out to evaluate system performance. The experimental results demonstrate
      that the system could accomplish intuitive motion control and motion scaling
      control, and that the control system is stable and reliable. CONCLUSIONS: The
      experiments performed on the MicroHand A robotic system yielded expected control
      results. The system satisfies the requirements of minimally invasive surgery.
      Intuitive motion control and motion scaling control under different kinematics
      for the master and slave have been implemented.

PMID- 21732499
TI  - A description of multiple family workshops for carers of people with anorexia
      nervosa.
AB  - Carers of people with eating disorders are uncertain about how best to help and
      express the need for information. Fifty per cent of carers (usually parents)
      exhibit clinically significant anxiety and/or depression. This may result from a
      difficulty coping with the manifestations of anorexia nervosa (AN) in the
      sufferer. In turn, eating disorder symptoms can be maintained by family reactions
      to the illness. Thus, carer's own symptoms, plus their uncertainty about how to
      help, impinge upon the AN sufferer, exacerbating their symptoms and behaviours.
      In this paper, we describe an intervention which uses cognitive behavioural
      therapy principles to alleviate carer's depression and anxiety and motivational
      interviewing to target behaviours that maintain eating disorder symptoms, for
      example high expressed emotion and poor communication. This is given in the form
      of an educational workshop for two families.

PMID- 21732500
TI  - A practical comparison of two types of family intervention: an exploratory RCT of
      family day workshops and individual family work as a supplement to inpatient care
      for adults with anorexia nervosa.
AB  - BACKGROUND: Little is known about the outcome of involving families in the
      treatment of adults with anorexia nervosa. Carers of people with anorexia nervosa
      experience significant levels of distress. This may contribute to unhelpful
      behaviours which maintain the illness. AIMS: To evaluate the effectiveness and
      acceptability of family workshops with educational and skills-based components as
      compared to individual family work. METHOD: An exploratory randomised controlled
      trial of two forms of family intervention was conducted for inpatients with
      anorexia nervosa (n = 48) and their family members on a specialised unit for
      adults. RESULTS: In both groups, there was an improvement in patients' BMI and a
      reduction in carers' distress. There were no differences between groups.
      CONCLUSION: Preliminary findings suggest that workshop-based intervention with
      two families might be as effective as an individually focused family
      intervention. This may offer a more cost-effective intervention for this
      treatment-resistant group.

PMID- 21732501
TI  - Family work in anorexia nervosa: a qualitative study of carers' experiences of
      two methods of family intervention.
AB  - BACKGROUND: Qualitative methods can aid in the development of complex
      interventions. AIMS: Qualitative methodology was used to examine treatment
      efficacy, carer satisfaction and process of change in carers of people with
      anorexia nervosa who participated in a randomised controlled trial (RCT)
      comparing individual family work (IFW) and multi-(dual) family workshops. METHOD:
      Twenty-three carers were interviewed. Themes were developed using Interpretive
      Phenomenological Analysis (IPA). RESULTS: Carers who worked with another family
      described this as beneficial. There was dissatisfaction about a lack of structure
      perceived in the IFW. Most carers felt the interventions helped them communicate,
      understand the illness and gain personal and familial insight. Although there was
      lack of consensus on the most helpful techniques, carers felt sessions should
      focus on individual relationships and practical guidance for challenging
      behaviour. CONCLUSIONS: Carers valued structured, skills-based interventions. The
      inclusion of multiple families may reduce carer blame and isolation and
      facilitate skills-based learning.

PMID- 21732502
TI  - Hydrogen-independent reductive transformation of carbohydrate biomass into gamma
      valerolactone and pyrrolidone derivatives with supported gold catalysts.

PMID- 21732504
TI  - Random walk to graphene (Nobel lecture).

PMID- 21732503
TI  - The particle-size dependence of the activation energy for decomposition of
      lithium amide.

PMID- 21732505
TI  - Graphene: materials in the Flatland (Nobel lecture).
AB  - Much like the world described in Abbott's "Flatland", graphene is a two
      dimensional object. And, as "Flatland" is "A Romance of Many Dimensions",
      graphene is much more than just a flat crystal. It possesses a number of unusual
      properties which are often unique or superior to those in other materials. In
      this brief lecture I would like to explain the reason for my (and many other
      people's) fascination with this material, and invite the reader to share some of
      the excitement I've experienced while researching it.

PMID- 21732506
TI  - Catalytic oxidation of silanes by carbon nanotube-gold nanohybrids.

PMID- 21732507
TI  - 3,7-Diazadibenzophosphole oxide: a phosphorus-bridged viologen analogue with
      significantly lowered reduction threshold.

PMID- 21732508
TI  - Asymmetric synthesis of isothiazoles through Cu catalysis: direct catalytic
      asymmetric conjugate addition of allyl cyanide to alpha,beta-unsaturated
      thioamides.

PMID- 21732509
TI  - Electric-field-responsive handle for large-area orientation of discotic liquid
      crystalline molecules in millimeter-thick films.

PMID- 21732510
TI  - The interaction of gold(I) cations with 1,3-dienes.

PMID- 21732511
TI  - Taking the aromaticity out of aromatic interactions.

PMID- 21732512
TI  - Palladium concave nanocubes with high-index facets and their enhanced catalytic
      properties.

PMID- 21732513
TI  - Stefan Hecht.

PMID- 21732514
TI  - Improved ruthenium-catalyzed amination of alcohols with ammonia: synthesis of
      diamines and amino esters.

PMID- 21732520
TI  - Atomic ensemble effects in electrocatalysis: the site-knockout strategy.
AB  - During an electrocatalytic reaction bonds are broken and formed, and this
      requires that the reactants, the intermediates formed at the elementary reaction
      steps, and the products interact with a given number of surface atoms of the
      catalyst. Modifying the number of groups with an adequate number of surface atoms
      in a suitable geometric arrangement for a determined reaction step to proceed may
      affect the activity and/or selectivity of the catalyst. Although separating
      purely geometric atomic ensemble effects from electronic effects is not
      straightforward, the insights extracted from a detailed investigation of atomic
      ensemble effects can have a profound impact in the determination of
      electrocatalytic reaction mechanisms and in the design of more active and more
      selective electrocatalysts. This Minireview illustrates, using cyanide-modified
      Pt(111) electrodes as an archetype, how eliminating only one kind of site from
      the surface (the site-knockout strategy) by means of a regular array of inert
      adsorbates can be used to successfully study atomic ensemble effects in
      electrocatalysis. The possible consequences for the design of more efficient and
      more selective electrocatalysts are also commented on.

PMID- 21732521
TI  - cis-trans Isomerisation of substituted aromatic imines: a comparative
      experimental and theoretical study.
AB  - The cis-trans isomerisation of N-benzylideneaniline (NBA) and derivatives
      containing a central C=N bond has been investigated experimentally and
      theoretically. Eight different NBA molecules in three different solvents were
      irradiated to enforce a photochemical trans--(hnu)-->cis isomerisation and the
      kinetics of the thermal backreaction cis--(Delta)-->trans were determined by NMR
      spectroscopy measurements in the temperature range between 193 and 288 K.
      Theoretical calculations using density functional theory and Eyring transition
      state theory were carried out for 12 different NBA species in the gas phase and
      three different solvents to compute thermal isomerisation rates of the thermal
      back reaction. While the computed absolute rates are too large, they reveal and
      explain experimental trends. Time-dependent density functional theory provides
      optical spectra for vertical transitions and excitation energy differences
      between trans and cis forms. Together with isomerisation rates, the latter can be
      used to identify "optimal switches" with good photochromicity and reasonable
      thermal stability.

PMID- 21732522
TI  - Quantitative study of non-covalent interactions at the electrode-electrolyte
      interface using cyanide-modified Pt(111) electrodes.

PMID- 21732523
TI  - Application study of medical robots in vascular intervention.
AB  - BACKGROUND: Based on the background of minimally invasive surgery and
      applications of medical robots, a vascular interventional robotic system has been
      developed that can be used in the field of vascular intervention. METHODS: The
      robotic system comprises a propulsion system, an image navigation system and a
      virtual surgery training system. Integration of the three systems constitutes a
      vascular intervention prototype robotic system used to carry out in vitro
      vascular intervention and animal experiments. RESULTS: On a transparent glass
      vascular model, a catheter was shown to enter an arbitrary branch of the vascular
      model with catheter motion meeting the requirements of clinical vascular
      intervention surgery (VIS); i.e. error band of catheter motion < 0.5 mm. In the
      animal experiments, 1.33-2.00 mm (4F-6F) diameter catheters were selectively
      inserted successfully into predefined targets in the animal, such as the renal,
      cardiovascular and cerebrovascular artery. Compared with conventional manual
      surgery, the time for robotic surgery is a little longer. There were no operative
      complications in the animal experiments. CONCLUSIONS: These simulation and animal
      study results demonstrate that this vascular interventional robotic system allows
      doctors to perform angiography remotely and prevents them from radiation
      exposure. The system may be the basis for further clinical applications of
      vascular intervention.

PMID- 21732524
TI  - Induced chronic hypoxia negates the pro-angiogenic effect of surface immobilized
      heparin in a polyurethane porous scaffold.
AB  - Porous scaffolds are frequently utilized in tissue regeneration. We have
      developed a polyurethane (PU) scaffold with a freely interconnecting porosity
      that can be modified with a covalently linked heparinized surface. The ability of
      this surface functionality to stimulate vessel and cellular growth into the PU
      scaffold has been evaluated by subcutaneous implantation of discs in the rat
      under normoxia and chronic hypoxia (hypobaric chamber) for 10 days. The
      heparinized surface alone was able to significantly increase vascularization and
      cellularization under normoxia (p < 0.05), but this response was negated by
      hypoxia. Addition of vascular endothelial growth factor to heparinized discs
      resulted in increased vascularity and cellularization under both conditions (p <
      0.05). This suggests that endogenous growth factor production was limiting under
      chronic hypoxia but that an angiogenic response could still occur with exogenous
      delivery of factors.

PMID- 21732525
TI  - A novel polymer-free paclitaxel-eluting stent with a nanoporous surface for rapid
      endothelialization and inhibition of intimal hyperplasia: Comparison with a
      polymer-based sirolimus-eluting stent and bare metal stent in a porcine model.
AB  - Hypersensitivity and inflammatory responses to polymers may be responsible for
      late stent thrombosis after implantation of a drug-eluting stent (DES). Polymer
      free DES may reduce the prevalence of these adverse reactions in vessels. We
      evaluated a polymer-free paclitaxel-eluting-stent with a nanoporous surface (nano
      PES) for endothelialization and inhibition of neointimal hyperplasia by optical
      coherence tomography (OCT) and pathology in a porcine model. Nano-PES with high
      dose (HD) and low-dose (LD) paclitaxel (1.0 MUg/mm(2) and 0.4 MUg/mm(2),
      respectively) was compared with a sirolimus-eluting stent (SES) and bare-metal
      stent (BMS) in a porcine model. Fifty-three stents (14 HD, 14 LD, 14 SES, 11 BMS)
      were implanted in 18 minipigs. At 14 days, nano-PES with HD and LD showed more
      complete endothelialization compared with SES. BMS had 100% endothelial coverage.
      At 28 days, a significant reduction in neointimal hyperplasia was detected by OCT
      in the nano-PES HD group compared with BMS. No benefit in prevention of the
      neointimal hyperplasia was observed in the nano-PES LD group. Nano-PES stents
      showed decreased deposition of fibrin and inflammation compared with SES.
      Pharmacokinetic studies revealed that nano-PES could effectively deliver the drug
      to the local coronary artery and it released the drug more rapidly than SES. Such
      a release profile was favorable for rapid endothelialization of nano-PES. The
      present study showed the nano-PES to be a new drug-delivery technology; that it
      used a nanoporous stent surface; that it offered desirable drug-elution
      properties without the use of polymers; that it may translate into an improved
      safety profile for next-generation DES.

PMID- 21732526
TI  - Photochemical cross-linking of plastically compressed collagen gel produces an
      optimal scaffold for corneal tissue engineering.
AB  - The experiments were designed to use photochemically cross-linked plastically
      compressed collagen (PCPCC) gel to support corneal epithelial cells. A
      plastically compressed collagen (PCC) scaffold was photo cross-linked by UVA in
      the presence of riboflavin to form a biomaterial with optimal mechanical
      properties. The breaking force, rheology, surgical suture strength, transparency,
      ultrastructure, and cell-based biocompatibility were compared between PCPCC and
      PCC gels. The breaking force increased proportionally with an increased
      concentration of riboflavin. The stress required to reach breaking point of the
      PCPCC scaffolds was over two times higher compared to the stress necessary to
      break PCC scaffolds in the presence of 0.1% riboflavin. Rheology results
      indicated that the structural properties of PCC remain unaltered after UVA cross
      linking. The PCC gels were more easily broken than PCPCC gels when sutured on to
      bovine corneas. The optical density values of PCPCC and PCC showed no significant
      differences (p > 0.05). SEM analyses showed that the collagen fibres within the
      PCPCC gels were similar in morphology to PCC gels. No difference in cell-based
      biocompatibility was seen between the PCPCC and PCC scaffolds in terms of their
      ability to support the ex vivo expansion of corneal epithelial cells or their
      subsequent differentiation evidenced by similar levels of cytokeratin 14. In
      conclusion, PCPCC scaffold is an optimal biomaterial for use in therapeutic
      tissue engineering of the cornea.

PMID- 21732527
TI  - In vitro biodegradation behavior of magnesium and magnesium alloy.
AB  - Magnesium has the potential to be used as degradable metallic biomaterial. For
      magnesium and its alloys to be used as biodegradable implant materials, their
      degradation rates should be consistent with the rate of healing of the affected
      tissue, and the release of the degradation products should be within the body's
      acceptable absorption levels. Conventional magnesium degrades rapidly, which is
      undesirable. In this study, biodegradation behaviors of high purity magnesium and
      commercial purity magnesium alloy AZ31 in both static and dynamic Hank's solution
      are systematically investigated. The in vitro test results show that magnesium
      purification and selective alloying are effective approaches to reduce the
      degradation rate of magnesium. In the static condition, the corrosion products
      accumulate on the materials surface as a protective layer, which results in a
      lower degradation rate than the dynamic condition. Anodized coating can
      significantly further reduce the degradation rate of magnesium. This study
      strongly indicates that magnesium can be used as degradable implant material as
      long as the degradation is controlled at a low rate. Magnesium purification,
      selective alloying, and anodized coating are three effective approaches to reduce
      the rate of degradation.

PMID- 21732528
TI  - A novel alkali metals/strontium co-substituted calcium polyphosphate scaffolds in
      bone tissue engineering.
AB  - Our purpose of this study is to develop potassium or sodium/strontium co
      substituted calcium polyphosphate (K/Sr-CPP or Na/Sr-CPP) bioceramics in
      application of bone repairing scaffold. The incorporation of K, Na, and Sr into
      CPP substrate via a calcining-sintering process was confirmed by X-ray
      diffractometry and inductively coupled plasma atomic emission spectroscopy. In
      vitro degradation study of co-substituted CPP indicated the incorporation of
      alkali metal elements promoted the degradability of CPP, and the scanning
      electron microscope showed the apatite-like minerals were precipitated on the
      surface of co-substituted CPP. The compress resistant strength of co-substituted
      CPP was elevated by dopants. The MTT assay and confocal laser-scanning microscope
      on osteoblasts culturing with co-substituted CPP showed no cytotoxicity. The cell
      proliferation on co-substituted CPP was even better than others. Thus, this co
      substituted CPP bioceramics might have potential of applications in orthopedic
      field.

PMID- 21732529
TI  - Preparation and characterization of novel poly(epsilon-caprolactone)/biphasic
      calcium phosphate hybrid composite microspheres.
AB  - Desirably porous biodegradable hybrid composite microspheres were fabricated for
      use in bone graft and bone substitute applications. In this study, novel
      poly(epsilon-caprolactone)/biphasic calcium phosphate (70/30) composite
      microspheres (PCL/BCP MPs) were prepared using the emulsion solvent-evaporation
      method. Throughout this process, the ammonium bicarbonate (NH4HCO3) content was
      changed to obtain the desired porous structure. However, to maintain the
      spherical shape, the NH4HCO3 content should not be higher than 5%. In the optical
      images of the PCL/BCP MPs, almost all the microparticles had a spherical shape,
      and the average diameter was about 600 MUm. The scanning electron microscopy and
      cross-sectional optical images showed that the pore density and pore diameter of
      PCL/BCP MPs increased with increasing initial NH4HCO3 concentrations. In the
      phase-composition analysis of the PCL/BCP MPs, which was characterized by X-ray
      diffraction and EDS, the two crystals BCP and PCL phases were shown to be
      miscible in PCL/BCP MPs. When the degradation of these microspheres was
      characterized, PCL/BCP MPs-0, PCL/BCP MPs-2, and PCL/BCP MPs-5 were found to
      display a sustained biodegradability, and the rate of degradation increased at
      higher initial NH4HCO3 concentrations. Proliferation of cells on three different
      sample types was assessed and compared, and based on these results, the PCL/BCP
      MPs-5 was chosen to study MG-63 osteoblast-cell adhesion, growth, and
      proliferation. Furthermore, confocal images indicated that the cells effectively
      adhered, spread, and proliferated on PCL/BCP MPs-5 during a 5-day culture period.

PMID- 21732530
TI  - Hybrid coaxial electrospun nanofibrous scaffolds with limited immunological
      response created for tissue engineering.
AB  - Electrospinning using synthetic and natural polymers is a promising technique for
      the fabrication of scaffolds for tissue engineering. Numerous synthetic polymers
      are available to maximize durability and mechanical properties (polyurethane)
      versus degradability and cell adhesion (polycaprolactone). In this study, we
      explored the feasibility of creating scaffolds made of bicomponent nanofibers
      from both polymers using a coaxial electrospinning system. We used a core of
      poly(urethane) and a sheath of a mixture of poly(epsilon-caprolactone) and
      gelatin, all dissolved in 1,1,1,3,3,3-hexafluror-2-propanol. These nanofibrous
      scaffolds were then evaluated to confirm their core-sheath nature and
      characterize their morphology and mechanical properties under static and dynamic
      conditions. Furthermore, the antigenicity of the scaffolds was studied to confirm
      that there is no significant foreign body response to the scaffold itself that
      would preclude its use in vivo. The results show the advantages of combining both
      natural and synethic polymers to create a coaxial scaffold capable of
      withstanding dynamic culture conditions and encourage cellular migration to the
      interior of the scaffold for tissue-engineering applications. Also, the results
      show that there is no significant immunoreactivity in vivo to the components of
      the scaffolds.

PMID- 21732531
TI  - Protein-conjugated acrolein as a biochemical marker of brain infarction.
AB  - The relationship between acrolein (CH(2) =CH-CHO) and brain infarction is the
      focus of this review. It has been found that acrolein is produced mainly within
      cells from polyamines by polyamine oxidases (PAOs), especially from spermine by
      spermine oxidase during cell damage, and that acrolein is more toxic than
      reactive oxygen species (ROS) in a cell culture system. Thus, the possibility
      that acrolein and PAOs are good biochemical markers of stroke was tested because
      there are no other reliable biochemical markers at the early stage of stroke.
      Levels of protein-conjugated acrolein (PC-Acro) and PAOs (acrolein-producing
      enzymes) were significantly increased in the plasma of stroke patients. The
      multiplied value of PC-Acro by PAOs was nearly parallel with the size of stroke.
      Furthermore, when the combined measurements of PC-Acro, interleukin-6 (IL-6) and
      C-reactive protein (CRP) were evaluated along with age using a receiver operating
      characteristic (ROC) curve, even silent brain infarction (SBI), which is a small
      brain infarction, was indicated with approximately 84% sensitivity and
      specificity. These findings clearly indicate that acrolein is strongly correlated
      with cell damage during brain infarction.

PMID- 21732532
TI  - A high-fat diet reduces ceramide synthesis by decreasing adiponectin levels and
      decreases lipid content by modulating HMG-CoA reductase and CPT-1 mRNA expression
      in the skin.
AB  - SCOPE: Molecules involved in skin function are greatly affected by nutritional
      conditions. However, the mechanism linking high-fat (HF) diets with these
      alterations is not well understood. This study aimed to investigate the molecular
      changes in skin function that result from HF diets. METHODS AND RESULTS: Sprague
      Dawley rats were fed HF diets for 28 days. The skin levels of ceramide, lipids
      and mRNAs involved in lipid metabolism were evaluated using TLC, oil red O
      staining and quantitative PCR, respectively. The serum adiponectin concentration
      was determined by ELISA. HF diets led to reduced ceramide levels and lowered skin
      lipid content. They also decreased mRNA levels of serine palmitoyltransferase
      (SPT) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the skin
      and those of peroxisome proliferator-activated receptor-alpha -PPAR-alpha), which
      upregulates SPT and HMG-CoA reductase expression. The HF diets reduced the serum
      concentration of adiponectin, which acts upstream of PPAR-alpha. Finally, these
      diets led to increased mRNA levels of carnitine palmitoyltransferase-1, the rate
      limiting enzyme that acts in beta-oxidation. CONCLUSION: Our study suggests that
      HF diets reduce ceramide and lipid synthesis in the skin by reducing levels of
      SPT and HMG-CoA reductase through lowered adiponectin and PPAR-alpha activity.
      Additionally, they decrease lipid content by enhancing beta-oxidation.

PMID- 21732533
TI  - High dose of dietary resveratrol enhances insulin sensitivity in healthy rats but
      does not lead to metabolite concentrations effective for SIRT1 expression.
AB  - SCOPE: trans-Resveratrol has been shown to improve insulin sensitivity and to
      enhance cellular glucose uptake. Evidence from recent studies indicates that
      these effects depend on SIRT1-pathways. METHODS AND RESULTS: Since ingestion of
      resveratrol leads to the presence of resveratrol and resveratrol metabolites in
      the body, we aimed at investigating (i) whether a daily dose of 300 mg
      resveratrol/kg body weight in healthy male Wistar rats for a period of 8 wk
      affects the selected parameters of glucose and lipid metabolism and (ii) whether
      the resulting plasma concentrations of resveratrol metabolites were effective in
      modulating SIRT1 expression. The dietary dose was based on the results from
      preceding toxicity studies. The results from the feeding experiment revealed
      plasma concentrations of resveratrol and its metabolites below 1 MUmol/L and
      showed that fasting glucose and insulin levels were decreased by 35 and 41%,
      respectively, in the resveratrol group compared with controls. Insulin
      sensitivity was enhanced by 70%, whereas liver SIRT1 protein expression was not
      affected. Treatment of HepG2 cells with 10 MUM resveratrol (1.49-fold) or its
      diglucuronides (1.21-fold) increased SIRT1 expression. CONCLUSION: These results
      suggest that the improved insulin sensitivity after dietary administration of 300
      mg resveratrol/kg body weight does not involve increased protein expression of
      SIRT1.

PMID- 21732534
TI  - Resveratrol inhibits migration and Rac1 activation in EGF- but not PDGF-activated
      vascular smooth muscle cells.
AB  - SCOPE: Migration of vascular smooth muscle cells (VSMC) reflects one of the
      initial steps in atherosclerosis. Resveratrol (RV) is suggested to mediate
      putative vasoprotective properties of red wine leading to the hypothesis that RV
      interferes with growth factor-induced migration of VSMC. METHODS AND RESULTS: We
      show here that RV (50 MUM) strongly reduces epidermal growth factor (EGF)- but
      not platelet-derived growth factor (PDGF)-induced VSMC migration using the wound
      healing technique. Accordingly, RV inhibited Rac1 activation and lamellipodia
      formation in response to EGF but not PDGF as shown by pull-down assays and
      fluorescence microscopy after actin staining with phalloidin-FITC, respectively.
      Since Src-family kinases and the phosphatidylinositol-3 kinase (PI3K) are
      reported to be crucial upstream mediators of Rac1 activation we examined the PI3K
      inhibitor wortmannin and the src kinase inhibitor SU6656 side-by-side with RV for
      their anti-migratory potential. Whereas src inhibition abrogated both EGF- and
      PDGF-triggered migration, wortmannin, like RV, was more effective in EGF- than
      PDGF-activated cells, suggesting that PI3K inhibition, previously shown for RV in
      growth factor-activated VSMC, contributes to the anti-migratory effect of RV in
      EGF-stimulated VSMC. CONCLUSION: This study is the first to discover an anti
      migratory potential of RV in EGF-activated VSMC that is most likely mediated via
      Rac1 inhibition.

PMID- 21732535
TI  - Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for
      metastatic dissemination of basal-like breast carcinomas.
AB  - Basal-like breast carcinoma is characterized by the expression of
      basal/myoepithelial markers, undifferentiated phenotype, highly aggressive
      behaviour and frequent triple negative status (ESR-, PR-, Her2neu-). We have
      previously shown that epithelial-mesenchymal transition (EMT) occurs in basal
      like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player
      and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2
      mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma
      cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear
      LOXL2 expression, and this subcellular distribution is significantly associated
      with distant metastatic incidence in basal-like breast carcinomas. LOXL2
      silencing in basal-like carcinoma cells induces a mesenchymal-epithelial
      transition (MET) associated with a decrease of tumourigenicity and suppression of
      metastatic potential. Mechanistic studies indicate that LOXL2 maintains the
      mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism
      involving transcriptional downregulation of Lgl2 and claudin1 and disorganization
      of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is
      a new candidate marker of basal-like carcinomas and a target to block metastatic
      dissemination of this aggressive breast tumour subtype.

PMID- 21732536
TI  - Synthesis and structure-activity relationships of constrained heterocyclic
      analogues of combretastatin A4.
AB  - A series of combretastatin A4 (CA4) analogues with a lactam or lactone ring fused
      to the trimethoxyphenyl or the B-phenyl moiety were synthesized in an efficient
      and stereoselective manner by using a domino Heck-Suzuki-Miyaura coupling
      reaction. The vascular-disrupting potential of these conformationally restricted
      CA4 analogues was assessed by various in vitro assays: inhibition of tubulin
      polymerization, modification of endothelial cell morphology, and disruption of
      endothelial cell cords. Compounds were also evaluated for their growth inhibitory
      effects against murine and human tumor cells. B-ring-constrained derivatives that
      contain an oxindole ring (in contrast to compounds with a benzofuranone ring) as
      well as analogues bearing a six-membered lactone core fused to the
      trimethoxyphenyl ring are endowed with significant biological activity. The most
      potent compound of this series (oxindole 9 b) is of particular interest, as it
      combines chemical stability and a biological activity profile characteristic of a
      vascular-disrupting agent.

PMID- 21732537
TI  - Tissue uptake study and photodynamic therapy of melanoma-bearing mice with a
      nontoxic, effective chlorin.
AB  - Chlorins have intense red absorptions and high tumor affinities that make them
      interesting candidates for photodynamic therapy (PDT) of cancer. This paper
      reports cytotoxicity, phototoxicity, in vitro cellular uptake, and in vivo
      biodistribution and PDT efficacy of a synthetic chlorin derivative (TCPCSO3H)
      towards Cloudman melanoma cells (S91). No cytotoxic effects were observed in
      vitro at concentrations up to 20 MUm, and no toxicity was observed in vivo in DBA
      mice with doses up to 2 mg kg-1. Pharmacokinetics and biodistribution of TCPCSO3H
      were evaluated in vivo in DBA mice bearing S91 tumors. TCPCSO3H demonstrated
      preferential accumulation in S91 mouse melanoma, with tumor-to-normal tissue
      ratios of 5 and 11 for muscle and skin, respectively, 24 h after intravenous
      injection of 2 mg kg-1. Photodynamic therapy performed under these conditions
      with 70 mW cm-2 diode laser irradiation at 655 nm for 25 min (total light
      dose=105 J cm-2) resulted in scab formation, followed by temporary or permanent
      (>60 days) tumor remission. According to the Kaplan-Meier analysis, the median
      survival time of the control group was 9 days, whereas that of the treated group
      was 38 days.

PMID- 21732538
TI  - Identification of a glycogen synthase kinase-3beta inhibitor that attenuates
      hyperactivity in CLOCK mutant mice.
AB  - Bipolar disorder is characterized by a cycle of mania and depression, which
      affects approximately 5 million people in the United States. Current treatment
      regimes include the so-called "mood-stabilizing drugs", such as lithium and
      valproate that are relatively dated drugs with various known side effects.
      Glycogen synthase kinase-3beta (GSK-3beta) plays a central role in regulating
      circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3beta. We
      designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides
      containing a piperidine ring that possess IC50 values in the range of 4 to 680 nM
      against human GSK-3beta. One of these compounds exhibits reasonable kinase
      selectivity and promising preliminary absorption, distribution, metabolism, and
      excretion (ADME) data. The administration of this compound at doses of 10 to 25
      mg kg-1 resulted in the attenuation of hyperactivity in
      amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of
      prepulse inhibition, similar to the effects found for valproate (400 mg kg-1) and
      the antipsychotic haloperidol (1 mg kg-1). We also tested this compound in mice
      carrying a mutation in the central transcriptional activator of molecular
      rhythms, the CLOCK gene, and found that the same compound attenuates locomotor
      hyperactivity in response to novelty. This study further demonstrates the use of
      inhibitors of GSK-3beta in the treatment of manic episodes of bipolar/mood
      disorders, thus further validating GSK-3beta as a relevant therapeutic target in
      the identification of new therapies for bipolar patients.

PMID- 21732539
TI  - [3H]UR-MK136: a highly potent and selective radioligand for neuropeptide Y Y1
      receptors.

PMID- 21732540
TI  - Synthesis of aryl-substituted naphthalene-linked pyrrolobenzodiazepine conjugates
      as potential anticancer agents with apoptosis-inducing ability.
AB  - A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1
      c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were
      designed, synthesized, and evaluated for their anticancer activity against a
      panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential,
      with some of them exhibiting particularly high activity (0.01-0.19 MUM). Thermal
      denaturation studies showed effective DNA binding capacity relative to DC-81. In
      assays for biological activity relating to cell-cycle distribution, these PBD
      conjugates induce G0/G1-phase arrest and also cause an increase in the levels of
      p53 and caspase-9 proteins, followed by apoptotic cell death. One conjugate in
      particular is the most promising candidate of the series, with the potential to
      be selected for further studies, either alone or in combination with existing
      anticancer therapies.

PMID- 21732541
TI  - Bromophycolide A targets heme crystallization in the human malaria parasite
      Plasmodium falciparum.

PMID- 21732542
TI  - Integration of CO2 capture and mineral carbonation by using recyclable ammonium
      salts.
AB  - A new approach to capture and store CO(2) by mineral carbonation using recyclable
      ammonium salts was studied. This process integrates CO(2) capture with mineral
      carbonation by employing NH(3), NH(4)HSO(4), and NH(4)HCO(3) in the capture,
      mineral dissolution, and carbonation steps, respectively. NH(4)HSO(4) and NH(3)
      can then be regenerated by thermal decomposition of (NH(4))(2)SO(4). The use of
      NH(4)HCO(3) as the source of CO(2) can avoid desorption and compression of CO(2).
      The mass ratio of Mg/NH(4)HCO(3)/NH(3) is the key factor controlling carbonation
      and the optimum ratio of 1:4:2 gives a conversion of Mg ions to hydromagnesite of
      95.5%. Thermogravimetric analysis studies indicated that the regeneration
      efficiency of NH(4)HSO(4) and NH(3) in this process is 95%. The mass balance of
      the process shows that about 2.63 tonnes of serpentine, 0.12 tonnes of
      NH(4)HSO(4), 7.48 tonnes of NH(4)HCO(3), and 0.04 tonnes of NH(3) are required to
      sequester 1 tonne of CO(2) as hydromagnesite.

PMID- 21732543
TI  - Recent progress on the growth mechanism of carbon nanotubes: a review.
AB  - Tremendous progress has been achieved during the past 20 years on not only
      improving the yields of carbon nanotubes and move progressively towards their
      mass production, but also on gaining a profound fundamental understanding of the
      nucleation and the growth processes. Parameters that influence the yield but also
      the quality (e.g., microstructure, homogeneity within a batch) are better
      understood. The influence of the carbon precursor, the reaction conditions, the
      presence of a catalyst, the chemical and physical status of the latter, and other
      factors have been extensively studied. The purpose of the present Review is not
      to list all the experiments reported in the literature, but rather to identify
      trends and provide a comprehensive summary on the role of selected parameters.
      The role of the catalyst occupies a central place in this Review as a careful
      control of the metal particle size, particle dispersion on the support, the
      metastable phase formed under reaction conditions, its possible reconstruction,
      and faceting strongly influence the diameter of the carbon nanotubes, their
      structure (number of walls, graphene sheet orientation, chirality), their
      alignment, and the yield. The identified trends will be compared with recent
      observations on the growth of graphene. Recent results on metal-free catalysts
      will be analyzed from a different perspective.

PMID- 21732544
TI  - Carbon nanotube mass production: principles and processes.
AB  - Our society requires new materials for a sustainable future, and carbon nanotubes
      (CNTs) are among the most important advanced materials. This Review describes the
      state-of-the-art of CNT synthesis, with a focus on their mass-production in
      industry. At the nanoscale, the production of CNTs involves the self-assembly of
      carbon atoms into a one-dimensional tubular structure. We describe how this
      synthesis can be achieved on the macroscopic scale in processes akin to the
      continuous tonne-scale mass production of chemical products in the modern
      chemical industry. Our overview includes discussions on processing methods for
      high-purity CNTs, and the handling of heat and mass transfer problems.
      Manufacturing strategies for agglomerated and aligned single-/multiwalled CNTs
      are used as examples of the engineering science of CNT production, which includes
      an understanding of their growth mechanism, agglomeration mechanism, reactor
      design, and process intensification. We aim to provide guidelines for the
      production and commercialization of CNTs. Although CNTs can now be produced on
      the tonne scale, knowledge of the growth mechanism at the atomic scale, the
      relationship between CNT structure and application, and scale-up of the
      production of CNTs with specific chirality are still inadequate. A
      multidisciplinary approach is a prerequisite for the sustainable development of
      the CNT industry.

PMID- 21732545
TI  - The Bidder's organ of the toad Rhinella arenarum (Amphibia, Anura). Presence of
      steroidogenic enzymes.
AB  - The Bidder's organ (BO) of male true toads of Bufonidae family is located in the
      anterior pole of the testis and it has been compared to a rudimentary ovary
      because of the presence of previtellogenic follicles. In some species, BO remains
      in both sexes, while in others only adult males preserve the structure. Several
      studies suggest that the development of BO is inhibited by the differentiation of
      the corresponding gonad. The purpose of this study is to describe morphological
      and histological variability of the BO of Rhinella arenarum and also analyze its
      steroidogenic capacity. Observations indicate that although most bidderian
      follicles are in pre vitellogenesis, there are others in early or late
      vitellogenesis. Moreover, we found that BOs weight was significantly lower in
      males during the pre-reproductive period and that there is no significant
      correlation between the weights of BO and the adjacent testis. We also analyzed
      the presence of steroidogenic enzymes using immunohistochemistry. Results
      indicate that all the follicles were immunoreactive with the antibody against
      aromatase, while only few of them were positive for the cytochrome P450 side
      chain cleavage. Furthermore, activities of 3beta-hydroxysteroid
      dehydrogenase/isomerase, cytochrome P450 17-hydroxylase, C17,20-lyase and
      aromatase were detected by the transformation of radioactive substrates into
      products. Taken together, these results confirm the steroidogenic capacity of the
      BO in adult males of R. arenarum.

PMID- 21732546
TI  - Mating does not influence reproductive investment, in a viviparous lizard.
AB  - Mating is crucial for females that reproduce exclusively sexually and should
      influence their investment into reproduction. Although reproductive adjustments
      in response to mate quality have been tested in a wide range of species, the
      effect of exposure to males and mating per se has seldom been studied.
      Compensatory mechanisms against the absence of mating may evolve more frequently
      in viviparous females, which pay higher direct costs of reproduction, due to
      gestation, than oviparous females. To test the existence of such mechanisms in a
      viviparous species, we experimentally manipulated the mating opportunity of
      viviparous female lizard, Lacerta (Zootoca) vivipara. We assessed the effect of
      mating on ovulation, postpartum body condition and parturition date, as well as
      on changes in locomotor performances and body temperatures during the breeding
      cycle. Female lizards ovulated spontaneously and mating had no influence on
      litter size, locomotor impairment or on selected body temperature. However,
      offspring production induced a more pronounced locomotor impairment and physical
      burden than the production of undeveloped eggs. Postpartum body condition and
      parturition dates were not different among females. This result suggests that
      gestation length is not determined by an embryonic signal. In the common lizard,
      viviparity is not associated with facultative ovulation and a control of litter
      size after ovulation, in response to the absence of mating.

PMID- 21732547
TI  - 3H-L-leucine transport by the promiscuous crustacean dipeptide-like
      cotransporter.
AB  - The crustacean intestine and hepatopancreas display a variety of solute transport
      mechanisms for transmembrane transfer of dietary contents from lumen to
      epithelial cytosol. An in vitro intestinal perfusion apparatus was used to
      characterize mucosal to serosoal (MS) and serosal to mucosal (SM) Zn(2+) 
      dependent (3)H-L-leucine transport by the intestine of the American lobster,
      Homarus americanus. Transmural 20 uM MS (3)H-L-leucine fluxes across lobster
      intestine were a hyperbolic function of luminal zinc concentration (1-50 uM)
      following Michaelis-Menten kinetics (K(m) = 2.67 +/- 0.74 uM; J(max) = 19.56 +/-
      2.22 pmol/cm(2) *min). Transmural 20 uM SM (3)H-L-leucine fluxes were not
      affected by serosal zinc, resulting in a highly significant stimulation of net
      amino acid transfer to the blood by luminal metal. MS fluxes of 20 uM (3)H-L
      leucine were also hyperbolic functions of luminal [Cu(2+)], [Mn(2+)], [Na(+)],
      and [H(+)]. MS flux of (3)H-L-leucine was a sigmoidal function of luminal [L
      leucine] and was stimulated by the addition of 20 uM luminal zinc at both pH 7.0
      and 5.5. A greater enhanced amino acid transport occurred at the lower pH 5.5. MS
      flux of 20 uM (3)H-L-leucine in the presence of 20 uM zinc was significantly
      inhibited by addition of 100 uM luminal glycylsarcosine, and MS flux of 20 uM
      (3)H-glycylsarcosine was inhibited by 100 uM L-leucine in the presence of 20 uM
      zinc. Results suggest that (3)H-L-leucine and metals form a complex (e.g., Leu-Zn
      Leu] that may functionally mimic dipeptides and use a dipeptide-like transporter
      during MS fluxes as suggested for fish and mammals.

PMID- 21732548
TI  - Use of the monoclonal antibody MOC-31 as an immunomarker for detecting metastatic
      adenocarcinoma in effusion cytology.
AB  - BACKGROUND: MOC-31 is an established immunologic marker with which to detect
      adenocarcinomas. The objective of the current study was to evaluate the use of
      MOC-31 in the diagnosis of metastatic adenocarcinoma in effusion specimens.
      METHODS: The authors evaluated cytologic specimens of effusions/washings in which
      MOC-31 immunostaining was performed on unstained cell block sections or
      Papanicolaou-stained cytospin preparations. Membranous staining with or without
      cytoplasmic staining was considered to be positive. The immunostaining results
      were correlated with the cytologic diagnoses and clinical follow-up data.
      RESULTS: A total of 215 effusions and washings were identified (cell blocks in
      162 cases, cytospin preparations in 53 cases, and both in 2 cases in which MOC-31
      immunostaining was performed). A total of 94 (44%) of the 215 cases were found to
      be positive for malignancy, including 87 metastatic adenocarcinomas. Specimens
      were positive for MOC-31 in 76 (87%; 55 cell blocks and 21 cytospin preparations)
      of 87 cases of metastatic adenocarcinoma. Eleven cases of metastatic
      adenocarcinoma were found to be negative for MOC-31 (4 cases from lung tumors, 2
      from stomach tumors, 2 from colon tumors, 2 from breast tumors, and 1 from a
      renal tumor). Minimal and/or focal cytoplasmic staining for MOC-31 was noted in
      13% of cases of reactive mesothelial cells/mesothelioma. The sensitivity of MOC
      31 for metastatic adenocarcinoma was 89%, the specificity was 100%, the negative
      predictive value was 92%, and the positive predictive value was 100%.
      CONCLUSIONS: MOC-31 alone was found to be highly sensitive for distinguishing
      reactive mesothelial cells/mesothelioma from metastatic adenocarcinoma in
      effusion specimens. Interpreting membranous MOC-31 staining as positive can help
      prevent confusion between reactive mesothelial cells/mesothelioma and metastatic
      adenocarcinoma. Cancer (Cancer Cytopathol) 2011;. (c) 2011 American Cancer
      Society.

PMID- 21732549
TI  - Cytologic-histologic correlation.
AB  - The process of cytologic-histologic correlation is highly valuable to the fields
      of both cytopathology and surgical pathology, because correlation provides a
      wealth of data that may be used to improve diagnostic testing and screening
      processes. In this study, overall improvement appeared to be driven largely by
      improvement in preanalytic Papanicolaou (Pap) test sampling, because longer
      institutional participation also was associated with improved sampling
      sensitivity. The authors hypothesized that Pap test sampling may have improved
      secondary to the introduction of liquid-based technology, which was implemented
      in many laboratories during the study time frame. Through the performance of
      continuous data tracking and retrospective root cause analysis to identify
      factors that may have influenced any observed changes in performance indicators,
      institutions may learn which initiatives are successful or unsuccessful. The
      future of correlation lies in the standardization of methods, the development of
      more formal and rigorous root cause analysis processes to determine system
      components underlying correlation discrepancies, and the active use of
      correlation data to redesign testing and screening processes for quality and
      patient safety improvement.

PMID- 21732550
TI  - Evaluation of chromosomal aberrations in patients with benign conditions and
      reactive changes in urinary cytology.
AB  - BACKGROUND: Fluorescence in situ hybridization (FISH) is routinely used to help
      clarify atypical urinary cytology. However, to the authors' knowledge, little is
      known regarding the frequency of chromosomal aberrations in non-neoplastic
      conditions that could potentially lead to false-positive FISH results. The
      objective of the current study was to evaluate the frequency of chromosomal
      aberrations in benign cells of the urinary tract using the UroVysion FISH test.
      METHODS: The authors analyzed 77 Papanicolaou-stained benign urine cytology
      specimens with reactive epithelial atypia using a FISH assay detecting the
      chromosomes 3, 7, and 17 and the gene locus 9p21. A positive test result was
      defined as an increased copy number of at least 2 chromosomes in >= 4 of 25
      cells, or > 10 cells with a tetraploid or octaploid pattern, or homozygous or
      heterozygous deletion of 9p21 (>= 12cells). RESULTS: FISH was positive in 27 of
      77 bladder washings (35.1%) including 25 of 65 bladder washings (40.5%) and 2 of
      15 voided urines (13.5%) from patients with irritative bladder (15 of 36
      patients), a history of radiotherapy (7 of 12 patients), nonspecific cystitis (3
      of 11 patients), hematuria (3 of 8 patients), and lithiasis (1 of 4 patients) .
      In 7 of 27 FISH-positive urothelial specimens, the positivity was solely due a
      polyploid pattern (tetraploid/octaploid pattern) in > 10 of the cells.
      CONCLUSIONS: Chromosomal aberrations can occur in reactive urothelial cells, with
      a tetraploid pattern being the most common. Even an aneuploid pattern of FISH
      signals does not always prove malignancy because it rarely occurs in reactive
      urothelial cells. Correlation of FISH results with cytomorphology and patient
      history is crucial to avoid false-positive diagnoses.

PMID- 21732551
TI  - Use of high-risk human papillomavirus testing in patients with low-grade squamous
      intraepithelial lesions.
AB  - BACKGROUND: The role of testing for high-risk human papillomavirus (HR HPV) when
      triaging women with a cytologic diagnosis of low-grade squamous intraepithelial
      lesion (LSIL) has not been well established. The objective of the current study
      was to correlate the status of HR HPV with the incidence of cervical
      intraepithelial neoplasia 2 and more severe lesions (CIN 2+) on tissue follow-up
      in women with LSIL. METHODS: A total of 1046 women with LSIL and HR HPV testing
      were identified in the database of a large teaching hospital within a 12-month
      period. HR HPV testing was performed using the Hybrid Capture 2 assay with 1
      relative light unit/cutoff as the cutoff. RESULTS: Of the 1046 women with LSIL
      and concurrent HR HPV testing, 82.3% tested positive for HR HPV, 91.1% of whom
      were women aged < 30 years and 73% of whom were women aged >= 30 years (P <
      .001). Cytologic and/or histologic follow-up was available in 979 (93.6%) women;
      25.5% had negative follow-up, 62.5% were found to have CIN 1 lesions, and 12.0%
      had CIN 2+ lesions. The sensitivity and negative predictive value of HR HPV
      status as a marker of CIN 2+ lesions were 98.3% and 98.9%, respectively. The
      colposcopy rate was 73.3% and 96.9% for women aged >= 30 years and women aged <
      30 years, respectively (P = .01). CONCLUSIONS: Using 1 RLU/CO as the cutoff
      value, HR HPV testing was found to be highly sensitive for detecting CIN 2+
      lesions in women with LSIL. The colposcopy rate was significantly lower in women
      aged >= 30 years compared with women aged < 30 years. Triaging with HR HPV
      testing may be indicated in women aged >= 30 years with LSIL cytology, but not in
      women aged < 30 years. Cancer (Cancer Cytopathol) 2011;. (c) 2011 American Cancer
      Society.

PMID- 21732552
TI  - In vivo post-translational modifications of recombinant mussel adhesive protein
      in insect cells.
AB  - Mussel adhesive proteins (MAPs) have been suggested as promising bioadhesives for
      diverse application fields, including medical uses. Previously, we successfully
      constructed and produced a new type of functional recombinant MAP, fp-151, in a
      prokaryotic Escherichia coli expression system. Even though the E. coli-derived
      MAP showed several excellent features, such as high production yield and
      efficient purification, in vitro enzymatic modification is required to convert
      tyrosine residues to l-3,4-dihydroxyphenyl alanine (dopa) molecules for its
      adhesive ability, due to the intrinsic inability of E. coli to undergo post
      translational modification. In this work, we produced a soluble recombinant MAP
      in insect Sf9 cells, which are widely used as an effective and convenient
      eukaryotic expression system for eukaryotic foreign proteins. Importantly, we
      found that insect-derived MAP contained converted dopa residues by in vivo post
      translational modification. In addition, insect-derived MAP also had other post
      translational modifications including phosphorylation of serine and hydroxylation
      of proline that originally occurred in some natural MAPs. To our knowledge, this
      is the first report on in vivo post-translational modifications of MAP containing
      dopa and other modified amino acid residues.

PMID- 21732553
TI  - Plasma biomarker identification in S-adenosylhomocysteine hydrolase deficiency.
AB  - S-Adenosylhomocysteine hydrolase (AHCY) deficiency is a rare congenital disorder
      in methionine metabolism clinically characterized by white matter atrophy,
      delayed myelination, slowly progressive myopathy, retarded psychomotor
      development and mildly active chronic hepatitis. In the present study, we
      utilized a comparative proteomics strategy based on 2-DE/MALDI-MS and LC/ESI-MS
      to analyze plasma proteins from three AHCY-deficient patients prior to and after
      receiving dietary treatment designed to alleviate disease symptoms. Obtained
      results revealed candidate biomarkers for the detection of myopathy specifically
      associated with AHCY deficiency, such as carbonic anhydrase 3, creatine kinase,
      and thrombospondin 4. Several proteins mediating T-cell activation and function
      were identified as well, including attractin and diacylglycerol kinase alpha.
      Further validation and functional analysis of identified proteins with clinical
      value would ensure that these biomarkers make their way into routine diagnosis
      and management of AHCY deficiency.

PMID- 21732554
TI  - A multiplexed bead assay for profiling glycosylation patterns on serum protein
      biomarkers of pancreatic cancer.
AB  - A multiplexed bead-based immunoassay was developed to simultaneously profile
      glycosylation patterns of serum proteins to investigate their usefulness as
      biomarkers for pancreatic cancer. The multiplex assay utilized protein-specific
      capture antibodies chemically coupled individually to beads labeled with specific
      amounts of fluorescent dye. Captured proteins were detected based on the extent
      and specific type of glycosylation as determined by successive binding of
      fluorescent lectin probes. Advantages to this technique include the fact that
      antibodies coupled to the beads had minimal nonspecific binding to the lectins
      ConA/SNA, avoiding the step of chemically blocking the antibody glycans and the
      bead assays were performed in a 96-well filter plate enabling high-throughput
      screening applications with improved reproducibility. The assay was tested with
      ConA and SNA lectins to examine the glycosylation patterns of alpha-1-beta
      glycoprotein (A1BG) and serum amyloid p (SAP) component for use as potential
      biomarkers for the detection of pancreatic cancer based on the results from prior
      biomarker studies. The results showed that the SNA response on the captured A1BG
      protein could distinguish chronic pancreatitis samples from pancreatic cancer
      with a p-value of 0.035 and for the SAP protein with SNA, a p-value of 0.026 was
      found between the signal of normal controls and the pancreatic cancer samples.
      For the ConA response, a decline in the signal for both proteins in the serum
      samples was found to distinguish pancreatic cancer from normal controls and renal
      cell carnoma samples (A1BG, p<0.05; and SAP, p<0.0001).

PMID- 21732555
TI  - Bile UPLC-MS fingerprinting and bile acid fluxes during human liver
      transplantation.
AB  - Bile flow restoration is a crucial step in the recovery process post
      transplantation of the liver. Here, metabolic trajectories based on changes in
      bile secretion - a known marker of functionality - have been utilised as an
      approach for discovering bile fluxes during transplantation. A total of ten liver
      transplants were monitored and from these 68 bile samples from both donors and
      recipients were collected and analysed using ultra-performance LC-MS in
      combination with multivariate statistical analysis. Based on the principal
      component scores constructed from the total bile fingerprint, differentiation of
      the bile acid concentrations before and after transplantation was detected. A
      trend was also observed, by constructing metabolic trajectories, whereby the post
      transplant profiles approached the position of pre-transplant profiles within 30
      60 min of the restoration of bile secretion function. The ten major conjugated
      bile acid salts were measured and a significant increase in concentrations of
      taurocholic acid and taurochenodeoxycholic acid were seen after transplantation.
      In addition, the ratios of secondary bile acids detected in gall bladder and
      hepatic bile were measured before and after transplantation. This study suggests
      that bile acid ratios in the donor liver at the pre-transplant and post
      transplant stage may be important and that profiling of secreted bile after
      transplantation may aid clinical assessment and progress post-transplantation.

PMID- 21732556
TI  - Isolation of compensatory inhibitor domain mutants to novel activation domain
      variants using the split-ubiquitin screen.
AB  - The control of transcription factor function plays an important role in the
      development of many processes in eukaryotes, such as drug resistance in fungi and
      human tumours undergoing chemotherapy. Detailed molecular mapping of the
      interactions between transcription factors and their protein partners can give
      important information about their mechanisms of action and reveal potential
      therapeutic targets. We devised a genetic screening system for mapping the
      interaction site between the Saccharomyces cerevisiae transcription factor
      inhibitor pair Gal4p and Gal80p. A novel Gal4p activation domain mutant, L868K,
      was produced, which prevented it interacting with Gal80p. The split-ubiquitin
      system was used with a mutant GAL80 library in order to screen for compensatory
      mutants in Gal80p which would restore binding with L868K. Five single amino acid
      residue compensatory mutations in Gal80p which restored the interaction with
      Gal4p(L868K) were isolated. These compensatory mutations were specific to L868K
      as they were unable to restore the interaction with two other Gal4p mutants that
      were incapable of interacting with Gal80p. Mutations within Gal80p that were
      capable of compensating for Gal4p (L868K) clustered inside a Gal80p surface
      cleft, supporting the idea that this area is important for Gal4p binding. Our
      data suggest a way to generate information about interaction sites that should be
      applicable to any transcription factor.

PMID- 21732557
TI  - Fractionation of the human plasma proteome for monoclonal antibody proteomics
      based biomarker discovery.
AB  - mAb proteomics, a reversed biomarker discovery approach, is a novel methodology
      to recognize the proteins of biomarker potential, but requires subsequent antigen
      identification steps. While in case of high-abundant proteins, it generally does
      not represent a problem, for medium or lower abundant proteins, the
      identification step requires a large amount of sample to assure the proper amount
      of antigen for the ID process. In this article, we report on the use of combined
      chromatographic and precipitation techniques to generate a large set of fractions
      representing the human plasma proteome, referred to as the Analyte Library, with
      the goal to use the relevant library fractions for antigen identification in
      conjunction with mAb proteomics. Starting from 500 mL normal pooled human plasma,
      this process resulted in 783 fractions with the average protein concentration of
      1 mg/mL. First, the serum albumin and immunoglobulins were depleted followed by
      prefractionation by ammonium sulfate precipitation steps. Each precipitate was
      then separated by size exclusion chromatography, followed by cation and anion
      exchange chromatography. The 20 most concentrated ion exchange chromatography
      fractions were further separated by hydrophobic interaction chromatography. All
      chromatography and precipitation steps were carefully designed aiming to maintain
      the native forms of the intact proteins throughout the fractionation process. The
      separation route of vitamin D-binding protein (an antibody proteomics lead) was
      followed in all major fractionation levels by dot blot assay in order to identify
      the library fraction it accumulated in and the identity of the antigen was
      verified by Western blot.

PMID- 21732558
TI  - Tunable mesoporous bragg reflectors based on block-copolymer self-assembly.

PMID- 21732559
TI  - Near-band-edge electroluminescence from heavy-metal-free colloidal quantum dots.

PMID- 21732560
TI  - Solution-processed heterojunction solar cells based on p-type PbS quantum dots
      and n-type Bi2 S3 nanocrystals.

PMID- 21732561
TI  - Carbon nanotubes with temperature-invariant creep and creep-recovery from -190 to
      970  degrees C.

PMID- 21732562
TI  - Effect of acene length on electronic properties in 5-, 6-, and 7-ringed
      heteroacenes.

PMID- 21732563
TI  - Highly stable porous polymer networks with exceptionally high gas-uptake
      capacities.

PMID- 21732564
TI  - Accelerated in vivo epidermal telomere loss in Werner syndrome.
AB  - Many data pertaining to the accelerated telomere loss in cultured cells derived
      from Werner syndrome (WS), a representative premature aging syndrome, have been
      accumulated. However, there have been no definitive data on in vivo telomere
      shortening in WS patients. In the present study, we measured terminal restriction
      fragment (TRF) lengths of 10 skin samples collected from extremities of 8 WS
      patients aged between 30 and 61 years that had been surgically amputated because
      of skin ulceration, and estimated the annual telomere loss. Whereas the values of
      TRF length in younger WS patients (in their thirties) were within the normal
      range, those in older WS patients were markedly shorter relative to non-WS
      controls. Regression analyses indicated that the TRF length in WS was
      significantly shorter than that in controls (p < 0.001). Furthermore, we found
      that TRF lengths in muscle adjacent to the examined epidermis were also
      significantly shorter than those of controls (p = 0.047). These data demonstrate
      for the first time that in vivo telomere loss is accelerated in systemic organs
      of WS patients, suggesting that abnormal telomere erosion is one of the major
      causes of early onset of age-related symptoms and a predisposition to sarcoma and
      carcinoma in WS.

PMID- 21732565
TI  - Put on your thinking cap: G-quadruplexes, helicases, and telomeres.

PMID- 21732566
TI  - Conserved role of Ras-GEFs in promoting aging: from yeast to mice.

PMID- 21732567
TI  - Ku circles the telomere?

PMID- 21732568
TI  - Ocular surface changes after lateral rectus muscle recession.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the changes in the integrated ocular
      surface/lacrimal gland unit after strabismus surgery. PATIENTS AND METHODS: The
      authors prospectively studied 23 patients undergoing lateral rectus muscle
      recession via fornix incision. At 1 week preoperatively and 1, 2, 3, and 4 months
      postoperatively, McMonnies' dry eye questionnaire, corneal fluorescein staining,
      corneal and conjunctival sensitivity with an esthesiometer, tear film break-up
      time, Schirmer I test, and impression cytology were performed. Impression
      cytology was performed in the inferotemporal and superotemporal bulbar
      conjunctiva and the goblet cell density (GCD) was measured. RESULTS: McMonnies'
      dry eye questionnaire scores increased significantly after surgery (P < .05 at 7
      days and 1, 2, and 3 months) and returned to baseline at 4 months
      postoperatively. A temporary increase in corneal staining was observed, but it
      returned to baseline by 2 months. The tear film break-up time score was decreased
      at 1 week postoperatively and recovered slowly, but did not return to normal by 4
      months. GCD in the inferotemporal area was significantly decreased until 2 months
      postoperatively. CONCLUSION: Tear film instability resulted from GCD depletion
      and conjunctival sensitivity could be one of the causative factors of ocular
      irritation symptoms after strabismus surgery. The ocular surface parameters
      returned to baseline at 4 months postoperatively.

PMID- 21732569
TI  - Selective laser trabeculoplasty in uncontrolled pseudoexfoliation glaucoma.
AB  - BACKGROUND AND OBJECTIVE: To assess the efficacy and safety of selective laser
      trabeculoplasty (SLT) in uncontrolled pseudoexfoliation glaucoma (PEXG). PATIENTS
      AND METHODS: Fifty-seven eyes (57 patients) with uncontrolled PEXG and intra
      ocular pressure (IOP) greater than 23 mm Hg underwent SLT. All received
      ophthalmic evaluation preoperatively and at intervals postoperatively. IOP was
      measured at 1 hour, 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively.
      During follow-up, patients were treated with topical anti-glaucoma medications as
      necessary. RESULTS: One year postoperatively, mean IOP in all patients decreased
      from 26.01 +/- 2.5 to 17.8 +/- 2.8 mm Hg (31.5%; P < .001). Mean medications per
      patient decreased from 2.8 to 2.3. Complications included conjunctival redness
      and infection within 1 day postoperatively in 30 eyes (67%). One hour after SLT
      treatment, an increase in IOP greater than 5 mm Hg was detected in two eyes
      (3.5%) and resolved within 24 hours with topical medication. CONCLUSION: SLT is
      safe and effective in patients with PEXG.

PMID- 21732574
TI  - The expanding role of phakic intraocular lenses-not just for the rare patient
      anymore.

PMID- 21732575
TI  - Change in visual acuity in albinism in the early school years.
AB  - PURPOSE: To determine whether binocular best-corrected visual acuity (B-BCVA)
      improves in the early school years in patients with albinism and whether this is
      related to type of albinism, ocular pigment, or appearance of the macula.
      METHODS: Patients with albinism seen between 5.5 and 9 years (Visit A) and 9.5
      and 14 years of age (Visit B), with visits separated by at least 2.5 years, were
      included. Type of albinism, B-BCVA, glasses wear, iris pigment and macular
      transparency grade, and presence or absence of an annular reflex and melanin in
      the macula were recorded. RESULTS: Mean B-BCVA was 20/84 at Visit A and 20/61 at
      Visit B (P < .001). B-BCVA improved in 80%. Improvement in B-BCVA and glasses
      wear, iris grade, macular grade, macular melanin, and annular reflex were weakly
      correlated. However, a moderate correlation was found between measured B-BCVA and
      iris grade at Visit A (r = 0.485, P < .001) and Visit B (r = 0.467, P < .001),
      and the presence of macular melanin at Visit A (r = 0.436, P < .001) and Visit B
      (r = 0.482, P < .001). CONCLUSIONS: B-BCVA often improves in albinism in the
      early school years and this observation should be included in counseling. The
      etiology is unknown but may be related to change in nystagmus, use of precise
      null point, developmental maturation, and/or some of the ocular characteristics
      evaluated in this study.

PMID- 21732576
TI  - Residual symptoms after surgery for unilateral congenital superior oblique palsy.
AB  - PURPOSE: To establish the surgical results and residual symptoms in 48 cases with
      unilateral congenital superior oblique muscle palsy that had surgical
      intervention to the vertical muscles alone. METHODS: Myectomy and concomitant
      disinsertion of the inferior oblique (IO) muscle was performed in 38 cases and
      myectomy and concomitant IO disinsertion and recession of the superior rectus
      muscle in the ipsilateral eye was performed in 10 cases. The preoperative and
      postoperative vertical deviation values and surgical results were compared.
      RESULTS: Of the patients who had myectomy and concomitant IO disinsertion, 74%
      achieved an "excellent" result, 21% a "good" result, and 5% a "poor" result
      postoperatively. The difference in deviation between preoperative and
      postoperative values was statistically significant (P < .001). Of the patients
      who had myectomy and concomitant inferior oblique disinsertion and ipsilateral
      superior rectus recession, 50% achieved an "excellent" result, 20% a "good"
      result, and 30% a "poor" result postoperatively. The difference in deviation
      between preoperative and postoperative values was statistically significant (P <
      .001). CONCLUSION: Both procedures are effective and successful in patients with
      superior oblique muscle palsy, but a secondary surgery may be required.

PMID- 21732577
TI  - Acute anterior uveitis and optic neuritis as ocular complications of influenza A
      infection in an 11-year-old boy.
AB  - The authors describe an 11-year-old boy developing bilateral acute anterior
      uveitis, papillitis in one eye, and neuroretinitis in the other eye after an
      upper respiratory tract infection of influenza A virus, possibly H1N1. Steroid
      pulse therapy resolved these conditions. The authors recommend alertness for
      visual blurring and ocular inflammation after influenza A infection.

PMID- 21732578
TI  - Challenges of managing sympathetic ophthalmia in a young child and the role of
      infliximab.
AB  - The authors report the difficult challenges and use of infliximab in the delayed
      presentation of a 21/2-year-old boy with a penetrating eye injury from a small
      ballpoint pen that led to sympathetic ophthalmia.

PMID- 21732580
TI  - Caring for veterans in rural areas: psychiatric nurses must seek out local
      resources.

PMID- 21732582
TI  - Simulation plays a leading role in education.

PMID- 21732585
TI  - Ligand influence over the formation of dinuclear [2+2] versus trinuclear [3+3]
      Cu(I) Schiff base macrocyclic complexes.
AB  - The preparation and characterization of three new macrocyclic ligands with
      pendant arms based on the [2+2] condensation of isophthalaldehyde and the
      corresponding triamine substituted at the central N-atom is reported. None of
      these new macrocyclic ligands undergo any equilibrium reaction, based on imine
      hydrolysis to generate [1+1] macrocyclic formation or higher oligomeric
      compounds, such as [3+3], [4+4], etc., at least within the time scale of days.
      This indicates the stability of the newly generated imine bond. In sharp
      contrast, the reaction of the [2+2] macrocyclic Schiff bases with Cu(I) generates
      the corresponding dinuclear Cu(I) complexes [Cu(2)(L(1))](2+), 1(2+);
      [Cu(2)(L(2))(CH(3)CN)(2)](2+), 2(2+); and [Cu(2)(L(3))(CH(3)CN)(2)](2+), 3(2+),
      together with their trinuclear Cu(I) homologues [Cu(3)(L(4))](3+), 4(3+);
      [Cu(3)(L(5))(CH(3)CN)(3)](3+), 5(3+); and [Cu(3)(L(6))(CH(3)CN)(3)](3+), 6(3+),
      where the [2+2] ligand has undergone an expansion to the corresponding [3+3]
      Schiff base that is denoted as L(4), L(5), or L(6). The conditions under which
      the dinuclear and trinuclear complexes are formed were analyzed in terms of
      solvent dependence and synthetic pathways. The new complexes are characterized in
      solution by NMR, UV-vis, and MS spectroscopy and in the solid state by X-ray
      diffraction analysis and IR spectroscopy. For the particular case of the L(2)
      ligand, MS spectroscopy is also used to monitor the metal assisted transformation
      where the dinuclear complex 2(2+) is transformed into the trinuclear complex
      5(3+). The Cu(I) complexes described here, in general, react slowly (within the
      time scale of days) with molecular oxygen, except for the ones containing the
      phenolic ligands 2(2+) and 5(3+) that react a bit faster.

PMID- 21732586
TI  - Palladium-catalyzed carbonation-diketonization of terminal aromatic alkenes via
      carbon-nitrogen bond cleavage for the synthesis of 1,2-diketones.
AB  - A palladium-catalyzed carbonation-diketonization reaction of terminal alkenes via
      carbon-nitrogen bond cleavage under an atmosphere of oxygen has been developed. A
      series of 1,2-diketones were readily prepared from the reaction of aromatic
      terminal alkenes with nitroalkanes.

PMID- 21732587
TI  - Solvothermal synthesis and characterization of polyselenidoarsenate salts of
      transition metal complex cations.
AB  - The polyselenidoarsenates [Fe(phen)(3)][As(2)Se(6)] (1),
      [Zn(phen)(dien)][As(2)Se(6)].2phen (2), [{Mn(phen)(2)}(2)(MU-eta(2),eta(2)
      AsSe(4))](2)[As(2)Se(6)].H(2)O (3), and [Ni(phen)(3)][As(2)Se(2)(MU-Se(3))(MU
      Se(5))] (4) (dien = diethylenetriamine and phen = 1,10-phenanthroline) were
      prepared by the reaction of As(2)O(3), Se, dien, and phen in the presence of
      transition metals in a methanol solvent under solvothermal conditions. Compounds
      1-3 consist of [As(2)Se(6)](2-) anions with [Fe(phen)(3)](2+),
      [Zn(phen)(dien)](2+), and [{Mn(phen)(2)}(2)(MU-eta(2),eta(2)-AsSe(4))](+) complex
      counter cations, respectively. The [As(2)Se(6)](2-) anion is formed from two
      As(III)Se(3) trigonal pyramids linked through two Se-Se bonds. Compound 3 is the
      first example of a mixed-valent selenidoarsenate(III,V) and exhibits the
      coexistence of As(III)Se(3) trigonal pyramidal and As(V)Se(4) tetrahedral units.
      Compound 4 is composed of a helical chain of [As(2)Se(2)(MU-Se(3))(MU-Se(5))(2
      )](infinity) and octahedral [Ni(phen)(3)](2+) cations. The [As(2)Se(2)(MU
      Se(3))(MU-Se(5))(2-)](infinity) chain is constructed from AsSe(+) units
      alternatively linked by MU-Se(3)(2-) and MU-Se(5)(2-) bridging ligands. When the
      structures of compounds 1-4 are compared, the transition metal ions show
      different structural directing effects during the synthesis of arsenic
      polyselenides in methanol. Compounds 1, 2, 3, and 4 exhibit semiconducting
      properties with band gaps of 1.88, 2.29, 1.82, and 2.01 eV, respectively.

PMID- 21732588
TI  - Direct assembly of hydrophobic nanoparticles to multifunctional structures.
AB  - We present a general process that allows convenient production of multifunctional
      composite particles by direct self-assembly of hydrophobic nanoparticles on host
      nanostructures containing high-density surface thiol groups. Hydrophobic
      nanoparticles of various compositions and combinations can be directly assembled
      onto the host surface through the strong coordination interactions between metal
      cations and thiol groups. The resulting structures can be further conveniently
      overcoated with a layer of normal silica to stabilize the assemblies and render
      them highly dispersible in water for biomedical applications. As the entire
      fabrication process does not involve complicated surface modification procedures,
      the hydrophobic ligands on the nanoparticles are not disturbed significantly so
      that they retain their original properties such as highly efficient luminescence.
      Many complex composite nanostructures with tailored functions can be efficiently
      produced by using this versatile approach. For example, multifunctional
      nonspherical nanostructures can be efficiently produced by using mercapto-silica
      coated nano-objects of arbitrary shapes as hosts for immobilizing functional
      nanoparticles. Multilayer structures can also be achieved by repeating the
      mercapto-silica coating and nanoparticle immobilization processes. Such assembly
      approach will provide the research community a highly versatile, configurable,
      scalable, and reproducible process for the preparation of various multifunctional
      structures.

PMID- 21732589
TI  - Physiological and proteomic analysis of salinity tolerance in Puccinellia
      tenuiflora.
AB  - Soil salinity poses a serious threat to agriculture productivity throughout the
      world. Studying mechanisms of salinity tolerance in halophytic plants will
      provide valuable information for engineering plants for enhanced salt tolerance.
      Monocotyledonous Puccinellia tenuiflora is a halophytic species that widely
      distributed in the saline-alkali soil of the Songnen plain in northeastern China.
      Here we investigate the molecular mechanisms underlying moderate salt tolerance
      of P. tenuiflora using a combined physiological and proteomic approach. The
      changes in biomass, inorganic ion content, osmolytes, photosynthesis, defense
      related enzyme activities, and metabolites in the course of salt treatment were
      analyzed in the leaves. Comparative proteomic analysis revealed 107 identities
      (representing 93 unique proteins) differentially expressed in P. tenuiflora
      leaves under saline conditions. These proteins were mainly involved in
      photosynthesis, stress and defense, carbohydrate and energy metabolism, protein
      metabolism, signaling, membrane, and transport. Our results showed that reduction
      of photosynthesis under salt treatment was attributed to the down-regulation of
      the light-harvesting complex (LHC) and Calvin cycle enzymes. Selective uptake of
      inorganic ions, high K(+)/Na(+) ratio, Ca(2+) concentration changes, and an
      accumulation of osmolytes contributed to ion balance and osmotic adjustment in
      leaf cells. Importantly, P. tenuiflora plants developed diverse reactive oxygen
      species (ROS) scavenging mechanisms in their leaves to cope with moderate
      salinity, including enhancement of the photorespiration pathway and thermal
      dissipation, synthesis of the low-molecular-weight antioxidant alpha-tocopherol,
      and an accumulation of compatible solutes. This study provides important
      information toward improving salt tolerance of cereals.

PMID- 21732590
TI  - Singlet oxygen generation by novel NIR BODIPY dyes.
AB  - Five novel near-infrared BODIPY dyes were prepared for improved singlet oxygen
      generation using thiophene and bromine. Theoretical, optical, photostable, and
      singlet oxygen generation characteristics of these dyes were assessed. Predicted
      excitation energies by TDDFT calculations were in good agreement (DeltaE ~ 0.06
      eV) with experimental data. All five dyes showed both excitation and emission in
      the NIR range. In particular, two dyes having sulfur and bromine atoms showed
      efficient singlet oxygen generation with high photostability.

PMID- 21732591
TI  - Highly functional group compatible Rh-catalyzed addition of arylboroxines to
      activated N-tert-butanesulfinyl ketimines.
AB  - The rhodium-catalyzed addition of readily accessible arylboroxines to N-tert
      butanesulfinyl ketimines derived from oxetan-3-one, N-Boc-azetidin-3-one, and
      isatins proceeds in high yields with excellent functional group compatibility.
      Moreover, high diastereoselectivities are observed for the additions to the N
      sulfinyl ketimines derived from isatins.

PMID- 21732592
TI  - Enhanced hypolipidemic effect and safety of red mold dioscorea cultured in deep
      ocean water.
AB  - Red mold dioscorea (RMD) produced by Monascus sp. was proven to be a
      hypolipidemic functional food. Deep ocean water (DOW), that is, water obtained
      from over 200 m deep in the ocean, was found to promote the growth of fungus via
      its mineral richness. On the basis of the advantages, this study used 650 m DOW
      as the culture water to culture Monascus purpuresus NTU 568 and produce the DOW
      RMD. The goal of this study is to compare the difference between DOW-RMD and
      reverse osmosis water-cultured RMD (ROW-RMD) on the hypolipidemic effect.
      Hyperlipidemic hamsters were fed a high-cholesterol diet and administered various
      doses of DOW-RMD or ROW-RMD for 8 weeks. After sacrifice, biochemical analyses in
      serum, liver, and feces were carried out. The results showed that DOW-RMD had a
      greater effect on lowering cholesterol levels and lipid peroxidation in serum and
      lipid plaque in heart aorta than ROW-RMD. However, DOW was likely to modulate the
      Monascus metabolite biosynthesis pathway toward the formation of hypolipidemic
      yellow pigments (such as monascin and ankaflavin) rather than red pigments and
      the mycotoxin citrinin. In addition, the DOW with higher Mg(2+) ion was proven to
      absorb into DOW-RMD; however, the accumulation of Mg(2+) ions should contribute a
      greater hypolipidemic effect to DOW-RMD. Comprehensively, the DOW-induced
      metabolism modulation and the ions of DOW were a benefit to the development of
      safe DOW-RMD with low citrinin levels and high hypolipidemic,
      antiatherosclerosis, and anti-fatty liver effects.

PMID- 21732593
TI  - Gold-catalyzed deacylative cycloisomerization reactions of 3-acylindole/ynes: a
      new approach for carbazole synthesis.
AB  - The synthesis of functionalized carbazoles through gold-catalyzed deacylative
      cycloisomerization of 3-acylindole/ynes is described. A mechanistic proposal for
      these transformations involving a novel carbonyl group facilitated heterolytic
      fragmentation upon the loss of an acylium ion intermediate is presented. The
      eliminated acylium ion species could be trapped by the organogold intermediate to
      afford acylcarbazoles.

PMID- 21732594
TI  - Cross-coupling of mesylated phenol derivatives with potassium
      alkoxymethyltrifluoroborates.
AB  - Cross-coupling of mesylated phenol derivatives with various potassium
      alkoxymethyltrifluoroborates has been achieved. The corresponding aryl and
      heteroaryl alkoxymethyl compounds have been obtained with equal facility with
      both electron-rich and electron-poor substituents on the activated alcohol.

PMID- 21732595
TI  - Synthesis and Suzuki-Miyaura cross-coupling reactions of potassium Boc-protected
      aminomethyltrifluoroborate with aryl and hetaryl halides.
AB  - Potassium Boc-protected aminomethyltrifluoroborate, a primary aminomethyl
      equivalent, was synthesized successfully through a "one-pot" process. With this
      trifluoroborate, Suzuki-Miyaura cross-coupling reactions were investigated with a
      variety of both aryl and hetaryl chlorides in good to excellent yields.

PMID- 21732596
TI  - On the elucidation of the mechanism of Vinca alkaloid fluorination in superacidic
      medium.
AB  - Detailed investigations on one of the key steps of the superacidic fluorination
      of Vinca alkaloids that is the origin of C20' activation are reported. While two
      different pathways can be envisioned for the emergence of the transient secondary
      carbocationic intermediate, isotopic labeling experiments unambiguously revealed
      the involvement of a 1,2-hydride shift mechanism.

PMID- 21732597
TI  - Efficient synthesis of 3,4-ethylenedioxythiophene (EDOT)-based functional pi
      conjugated molecules through direct C-H bond arylations.
AB  - A variety of 3,4-ethylenedioxythiophene (EDOT)-based pi-conjugated molecules were
      efficiently synthesized in good yields through Pd-catalyzed direct C-H bond
      arylations, wherein a detailed synthetic investigation, including the screening
      of various kinds of palladium catalysts, ligands, additives, and solvents, was
      carried out. In addition, the spectroscopic and electrochemical properties of
      these EDOT-containing molecules were also investigated.

PMID- 21732598
TI  - 1,3-Dipolar cycloaddition of hydrazones with alpha-oxo-ketenes: a three-component
      stereoselective entry to pyrazolidinones and an original class of spirooxindoles.
AB  - Stereodefined monocyclic, spirobicyclic, and bis-spirotricyclic pyrazolidin-3
      ones can be prepared efficiently by a three-component reaction involving a 1,3
      dipolar cycloaddition of azomethine imines obtained from hydrazones with alpha
      oxo-ketene dipolarophiles generated in situ. The reaction allows the creation of
      four covalent bonds and two contiguous chiral quaternary centers with excellent
      diastereoselectivity in a single catalyst/additive-free, highly atom-economical
      transformation. From a fundamental point of view, the reaction introduces alpha
      oxo-ketenes as effective dipolarophiles in 1,3-dipolar cycloadditions.

PMID- 21732599
TI  - Direct detection of biologically significant thiols and disulfides with
      manganese(IV) chemiluminescence.
AB  - The quantification of low-molecular mass thiols and disulfides involved in
      cellular redox processes is hindered by oxidation or degradation of analytes
      during conventional sample preparation steps (including deproteinization and
      derivatization). Researchers therefore seek techniques that minimize sample
      handling and permit direct detection of thiols and disulfides within a single
      chromatographic separation. We demonstrate a new HPLC procedure for these
      biologically important analytes that incorporates direct chemiluminescence
      detection with a manganese(IV) reagent. A mixture of seven thiols and disulfides
      (cysteine, N-acetylcysteine, homocysteine, glutathione (GSH), glutathione
      disulfide (GSSG), cystine, and homocystine) in their native forms were separated
      using a C18 column within 20 min. Detection limits for these analytes ranged from
      5 * 10(-8) to 1 * 10(-7) M, and the precision for retention times and peak areas
      was excellent, with relative standard deviations of less than 0.3% and 2%,
      respectively. This approach was employed to determine two key biomarkers of
      oxidative stress, GSH and GSSG, in whole blood taken from 12 healthy volunteers.
      Samples were deproteinized, centrifuged, and diluted prior to analysis using a
      simple procedure that was shown to avoid significant artificial oxidation of GSH.

PMID- 21732600
TI  - Combating bacterial colonization on metals via polymer coatings: relevance to
      marine and medical applications.
AB  - Metals are widely used in engineering as well as medical applications. However,
      their surfaces are easily colonized by bacteria that form biofilms. Among the
      numerous concerns with biofilm formation, biocorrosion is of particular
      importance in industry, because structural integrity may be compromised, leading
      to technical failures. In the food industry and medical field, biofilms also pose
      health risks. To inhibit bacterial colonization, the surfaces of metals can be
      coated with a polymeric layer which is antiadhesive and/or bactericidal. This
      article describes polymers that have these desired properties and the
      methodologies for immobilizing them on metal surfaces of relevance to the marine
      and medical fields. The focus is on polymer coatings that have a high degree of
      stability in aqueous medium and do not leach out. The efficacies of the different
      polymer coatings against bacteria commonly encountered in marine (Desulfovibrio
      desulfuricans) and medical applications (Staphylococcus aureus, Staphylococcus
      epidermidis and Escherichia coli) are demonstrated.

PMID- 21732601
TI  - Homoleptic tetranuclear complexes of divalent tin and lead tetraolates.
AB  - Homoleptic tetranuclear complexes of divalent tin and lead tetraolates,
      M(4)(hfpt)(2) [M = Sn (1) and Pb (2); hfpt(4-) is an anion of 1,1,1,5,5,5
      hexafluoropentane-2,2,4,4-tetraol], have been obtained in high yield from the
      corresponding (trimethylsilyl)amides. The solid-state structures of 1 and 2
      contain discrete molecules in which a butterfly tetrahedron of metal atoms is
      sandwiched between two tetraolate ligands acting in tetradentate mode. The lone
      pair Sn(2+) and Pb(2+) cations exhibit pyramidal coordination of four ligand
      oxygen atoms. A multinuclear NMR study unambiguously confirmed that metal
      tetraolates retain their polynuclear structure in solution of even coordinating
      solvents. An interesting example of the strong through-space coupling between
      (19)F of the tetraolate trifluoromethyl groups and (117/119)Sn or (207)Pb nuclei
      was found. Both compounds were shown to have clean, low-temperature decomposition
      that results in crystalline oxides SnO(2) and PbO, respectively, for 1 and 2.
      This work demonstrates the remarkable coordination properties of the tetraolate
      ligand that can be utilized for the preparation of a wide variety of poly- and
      heterometallic complexes. Decomposition studies revealed a great potential of
      metal tetraolate complexes as prospective molecular precursors for the soft
      chemistry approach to oxide materials.

PMID- 21732602
TI  - A novel tunable green- to yellow-emitting beta-YFS:Ce3+ phosphor for solid-state
      lighting.
AB  - A Ce(3+)-activated fluorosulfide phosphor (beta-YFS:Ce(3+)) was synthesized by
      solid-state reaction in a sealed tube. The crystal structure has been refined
      from the XRD profiles and there are two different crystallographic rare earth
      sites, namely, Y(1) and Y(2), where the Ce(3+) ions occupied. The emission band
      with a maximum at 495 nm of beta-Y(0.99)Ce(0.01)FS phosphor was characterized by
      the 4f-5d transitions of Ce(3+) ion. With increasing Ce(3+) concentration, the
      emission variations were observed from 495 to 547 nm. When beta-YFS:Ce(3+)
      phosphors were utilized to incorporate with n-UV/blue chip, greenish-white light
      with color rendering index of 65-77 were obtained. The results indicate that the
      tunable green- to yellow-emitting beta-YFS:Ce(3+) can serve as a potential
      phosphor for incorporation in fabrication for solid-state lighting. The
      preparation, spectroscopic characterization, quantum efficiency, thermal
      quenching behavior, and related LED device data are also presented.

PMID- 21732603
TI  - Probabilistic design of a near-surface CO2 leak detection system.
AB  - A methodology is developed for predicting the performance of near-surface CO(2)
      leak detection systems at geologic sequestration sites. The methodology
      integrates site characterization and modeling to predict the statistical
      properties of natural CO(2) fluxes, the transport of CO(2) from potential
      subsurface leakage points, and the detection of CO(2) surface fluxes by the
      monitoring network. The probability of leak detection is computed as the
      probability that the leakage signal is sufficient to increase the total flux
      beyond a statistically determined threshold. The methodology is illustrated for a
      highly idealized site monitored with CO(2) accumulation chamber measurements
      taken on a uniform grid. The TOUGH2 code is used to predict the spatial profile
      of surface CO(2) fluxes resulting from different leakage rates and different soil
      permeabilities. A response surface is fit to the TOUGH2 results to allow
      interpolation across a continuous range of values of permeability and leakage
      rate. The spatial distribution of leakage probability is assumed uniform in this
      application. Nonlinear, nonmonotonic relationships of network performance to soil
      permeability and network density are evident. In general, dense networks (with
      ~10-20 m between monitors) are required to ensure a moderate to high probability
      of leak detection.

PMID- 21732604
TI  - Biotic and abiotic pathways of phosphorus cycling in minerals and sediments:
      insights from oxygen isotope ratios in phosphate.
AB  - A key question to address in the development of oxygen isotope ratios in
      phosphate (delta(18)O(p)) as a tracer of biogeochemical cycling of phosphorus in
      ancient and modern environments is the nature of isotopic signatures associated
      with uptake and cycling of mineral-bound phosphate by microorganisms. Here, we
      present experimental results aimed at understanding the biotic and abiotic
      pathways of P cycling during biological uptake of phosphate sorbed to
      ferrihydrite and the selective uptake of sedimentary phosphate phases by
      Escherichia coli and Marinobacter aquaeolei. Results indicate that a significant
      fraction of ferrihydrite-bound phosphate is biologically available. The fraction
      of phosphate taken up by E. coli attained an equilibrium isotopic composition in
      a short time (<50 h) due to efficient O-isotope exchange (between O in PO(4) and
      O in water; that is, actual breaking and reforming of P-O bonds) (biotic
      pathway). The difference in isotopic composition between newly equilibrated
      aqueous and residual sorbed phosphate groups promoted the ion exchange (analogous
      to isotopic mixing) of intact phosphate ions (abiotic pathway) so that this
      difference gradually became negligible. In sediment containing different P
      phases, E. coli extracted loosely sorbed phosphate first, whereas M. aquaeolei
      preferred Fe-oxide-bound phosphate. The presence of bacteria always imprinted a
      biotic isotopic signature on the P phase that was taken up and cycled. For
      example, the delta(18)O(p) value of loosely sorbed phosphate shifted gradually
      toward equilibrium isotopic composition. The delta(18)O(p) value of Fe-oxide
      bound phosphate, however, showed only slight changes initially but, when new Fe
      oxides were formed, coprecipitated/occluded phosphate retained delta(18)O values
      of the aqueous phosphate at the time of formation of new Fe oxides.
      Concentrations and isotopic compositions of authigenic and detrital phosphates
      did not change, suggesting that these phosphate phases were not utilized by
      bacteria. These findings support burgeoning applications of delta(18)O(p) as a
      tracer of phosphorus cycling in sediments, soils, and aquatic environments and as
      an indicator of paleo- environmental conditions.

PMID- 21732605
TI  - Orthogonally dual-clickable Janus nanoparticles via a cyclic templating strategy.
AB  - Synthetic asymmetrical systems, Janus particles and patchy particles, are capable
      of undergoing hierarchical assembly processes that mimic those of Nature, to
      serve as switchable devices, optical probes, phase-transfer catalysts, and
      multifunctional drug carriers, each of which benefits from opposing surface
      patterns that behave differently. Production of nanometer-sized Janus particles
      that are equipped with efficient chemistries remains a challenge. A robust Janus
      faced polymer nanoparticle framework that presents two orthogonally click
      reactive surface chemistries has been generated by a recyclable strategy that
      involves reactive functional group transfer by templating against gold
      nanoparticle substrates. This anisotropic functionalization approach is
      compatible with a wide range of soft materials, providing Janus nanoparticles for
      the construction of dual-functionalized devices by accurately controlling
      chemical functionality at the nanoscopic level.

PMID- 21732606
TI  - Theranostic nanoparticles engineered for clinic and pharmaceutics.
AB  - Nanomedicine is the manipulation of human biological systems at the molecular
      level using nanoscale or nanostructured materials. Because nanoscale materials
      interact effectively with biological systems, the use of nanodiagnostics and
      nanotherapeutics may overcome many intractable health challenges. A variety of
      nanoparticles have been designed with modifiable functional surfaces and
      bioactive cores. The engineering of nanoparticles can result in several
      advantageous therapeutic and diagnostic properties including enhanced permeation
      and retention in the circulatory system, specific delivery of drugs to target
      sites, highly-efficient gene transfection, and enhanced medical imaging.  These
      nanoscale materials offer the opportunity to detect chronic diseases early and to
      monitor the therapeutic effects of nanoformulated drugs used in the clinic. Many
      of these novel nanoparticles contain both drug(s) and imaging agent(s) within an
      individual nanoparticle for simultaneous disease diagnosis and therapy. Further
      integration of therapeutic compounds with diagnostic agents into theranostic
      nanoparticles would be highly beneficial.  However, the unique physiochemical
      properties that make nanomaterials attractive for therapy and diagnosis may be
      also associated with potential health hazards. Our research has demonstrated that
      the biological response to nanomaterials is related to many factors including
      exposure levels, systemic accumulation and excretion profiles, tissue and organ
      distribution, and the age of the test subject. Therefore, when engineering new
      nanomaterials for clinical use, researchers need to consider these factors to
      minimize toxicity of nanoparticles in these applications. We have fabricated and
      evaluated nanomaterials such as cationic amphiphilic polymers and
      metallofullerenes that demonstrate both high efficiency and low toxicity in gene
      therapy and/or chemotherapy. In this Account, we describe the development of
      theranostic nanomaterials with low toxicity and illustrate their potential use as
      novel nanomedicines in translational research.

PMID- 21732607
TI  - Direct measurement of off-state trapping rate fluctuations in single quantum dot
      fluorescence.
AB  - Fluorescence decay times measured during the off-state of single CdSe/ZnS quantum
      dot blinking are found to decrease with increasing off-state duration,
      contradicting the charging model widely considered to explain the blinking
      phenomenon. The change in the nonradiative process of a short off-state duration
      compared to a long one is investigated here through simultaneous measurement of
      fluorescence decay and blinking behavior. The results are investigated in the
      framework of two models based on fluctuating trapping rates.

PMID- 21732608
TI  - A versatile solvent-free mechanochemical route to the synthesis of heterometallic
      dicyanoaurate-based coordination polymers.
AB  - The solid-state mechanochemical method was proved to be a fast, simple, and
      efficient route to the synthesis of heterometallic [Au(CN)(2)]-based coordination
      polymers. Thus, a series of mixed-metal complexes, such as KCo[Au(CN)(2)](3),
      KNi[Au(CN)(2)](3), Cu(H(2)O)(2)[Au(CN)(2)](2), and Zn[Au(CN)(2)](2), was obtained
      by grinding stoichiometric amounts of K[Au(CN)(2)] and transition metal(II)
      chlorides. This solid-state method rapidly yields pure dicyanoaurate-based
      compounds, also in cases when the aqueous solution synthesis leads to an
      unseparable mixture of products. In addition, in some cases, the solid state
      reaction was faster than the corresponding solvent-based reaction. This
      mechanochemical method can be applied also to main group metals to obtain various
      cyanoaurate-based heterometallic coordination polymers, such as
      Me(2)Sn[Au(CN)(2)](2) and Ph(3)Sn[Au(CN)(2)]. For the 2:1 mixture of K[Au(CN)(2)]
      and Me(2)SnCl(2), the dramatic enhancement of the reaction rate by the presence
      of a minor amount of water was noticed. In Ph(3)Sn[Au(CN)(2)], as was revealed by
      single-crystal X-ray diffraction, each Ph(3)Sn unit is linked to two others by
      two Au(CN)(2) bridges via Sn-N bonds to form an infinite cyanide-bridged chain.
      There are no Au...Au contacts between the chains due to the sterical hindrance of
      the phenyl groups. A dehydrated blue Co[Au(CN)(2)](2) complex was obtained during
      grinding or heating of the moderate-pink Co(H(2)O)(2)[Au(CN)(2)](2) complex. This
      complex displays a vapochromic response when exposed to a variety of organic
      solvents, as well as water and ammonia vapors.

PMID- 21732609
TI  - Asymmetric propargylation of ketones using allenylboronates catalyzed by chiral
      biphenols.
AB  - Chiral biphenols catalyze the enantioselective asymmetric propargylation of
      ketones using allenylboronates. The reaction uses 10 mol % of 3,3'-Br(2)-BINOL as
      the catalyst and allenyldioxoborolane as the nucleophile, in the absence of
      solvent, and under microwave irradiation to afford the homopropargylic alcohol.
      The reaction products are obtained in good yields (60-98%) and high enantiomeric
      ratios (3:1-99:1). Diastereoselective propargylations using chiral racemic
      allenylboronates result in good diastereoselectivities (dr >86:14) and
      enantioselectivities (er >92:8) under the catalytic conditions.

PMID- 21732610
TI  - Aptamer-conjugated DNA icosahedral nanoparticles as a carrier of doxorubicin for
      cancer therapy.
AB  - DNA can be used to nanofabricate three-dimensional (3D) polyhedra. A variety of
      applications of 3D DNA assemblies have been proposed. Drug encasulation and
      intracellular delivery using DNA nanoparticles, however, have remained a
      challenge. Here, we create a distinct five-point-star motif and aptamer
      conjugated six-point-star motif using well-used primer sequences to
      intermolecularly construct DNA icosahedra as a nanocarrier for doxorubicin.
      Aptamer-conjugated doxorubicin-intercalated DNA icosahedra (Doxo@Apt-DNA-icosa)
      show an efficient and specific internalization for killing epithelial cancer
      cells.

PMID- 21732611
TI  - Synthesis, structures, and magnetism of copper(II) and manganese(II) coordination
      polymers with azide and pyridylbenzoates.
AB  - Three transition-metal coordination polymers with azide and/or carboxylate
      bridges have been synthesized from 4-(3-pyridyl)benzoic acid (4,3-Hpybz) and 4-(4
      pyridyl)benzoic acid (4,4-Hpybz) and characterized by X-ray crystallography and
      magnetic measurements. Compound 1, [Cu(4,3-pybz)(N(3))](n), consists of 2D
      coordination networks in which the uniform chains with (MU-EO-N(3))(MU-COO)
      double bridges are cross-linked by the 4,3-pybz ligands. Compound 2, [Cu(2)(4,4
      pybz)(3)(N(3))](n).3nH(2)O, consists of 2-fold interpenetrated 3D coordination
      networks with the alpha-Po topology, in which the six-connected dinuclear motifs
      with mixed (MU-EO-N(3))(MU-COO)(2) (EO = end-on) triple bridges are linked by the
      4,4-pybz spacers. Compound 3, [Mn(4,4-pybz)(N(3))(H(2)O)(2)](n), contains 2D
      manganese(II) coordination networks in which the chains with single MU-EE-N(3)
      bridges (EE = end-to-end) are interlinked by the 4,4-pybz ligands, and the
      structure also features a 2D hydrogen-bonded network in which Mn(II) ions are
      linked by double triatomic bridges, (MU-EE-N(3))(O-H...N) and (O-H...O)(2).
      Magnetic studies indicated that the mixed azide and carboxylate bridges in 1 and
      2 induce ferromagnetic coupling between Cu(II) ions and that 3 features
      antiferromagnetic coupling through the EE-azide bridge. In addition, compound 1
      exhibits antiferromagnetic ordering below 6.2 K and behaves as a field-induced
      metamagnet. A magnetostructural survey indicates a general trend that the
      ferromagnetic coupling through the mixed bridges decreases as the Cu-N-Cu angle
      increases.

PMID- 21732612
TI  - Connecting the nanodots: programmable nanofabrication of fused metal shapes on
      DNA templates.
AB  - We present a novel method for producing complex metallic nanostructures of
      programmable design. DNA origami templates, modified to have DNA binding sites
      with a uniquely coded sequence, were adsorbed onto silicon dioxide substrates.
      Gold nanoparticles functionalized with the cDNA sequence were then attached.
      These seed nanoparticles were later enlarged, and even fused, by electroless
      deposition of silver. Using this method, we constructed a variety of metallic
      structures, including rings, pairs of bars, and H shapes.

PMID- 21732613
TI  - Anti-stress effects of Glycine tomentella Hayata in tilapia: inhibiting COX-2
      expression and enhancing EPA synthesis in erythrocyte membrane and fish growth.
AB  - The objective of this study was to elucidate the in vivo effects of the ethanol
      extract of wooly Glycine tomentella Hayata (GTE) root on tilapia to elucidate
      whether GTE has antistress activity. Tilapia as an animal model were fed with or
      without GTE, then injected with lipopolysaccharide (LPS) or ammonium chloride
      (NH(4)Cl). The tilapia were exposed to 100 mg/L of aqueous NH(4)Cl, and/or acute
      cold stress. Growth parameters of the tilapia were measured during the feeding
      trials. Tilapia injected with GTE (20 MUg/g of fish), NH(4)Cl (100 MUg/g of fish)
      and/or LPS (1 MUg/g of fish) were then sampled 2 h poststimulation. GTE
      significantly inhibited cyclooxygenase-2 expression and hemoglobin (Hb) dimer
      formation (36 kDa). GTE also improved growth and blood viscosity and upregulated
      eicosapentaenoic acid content of erythrocytes. The in vivo results indicated that
      GTE (20 MUg/g of fish) can be applied as a stress-tolerance enhancing agent for
      the aquaculture industry.

PMID- 21732614
TI  - Star-shaped pyrrole-fused tetrathiafulvalene oligomers: synthesis and redox, self
      assembling, and conductive properties.
AB  - A series of star-shaped pyrrole-fused tetrathiafulvalene (TTF) oligomers 1-3 was
      synthesized via an S(N)Ar reaction of fluorinated benzenes with the pyrrolyl
      sodium salts. Electrochemical and chemical oxidations of 1-3 revealed that a
      radical cation moiety on each TTF unit was successfully accumulated in all
      oligomers. Self-assembled structures of neutral and oxidized species were
      characterized by SEM and XRD, and their conductive properties of the iodine-doped
      1-3 as well as an intermolecular mixed-valence ion radical salt were
      investigated.

PMID- 21732615
TI  - Chirped pulse Fourier transform microwave study of 2,2,2-trifluoroethyl formate.
AB  - The rotational spectra of 2,2,2-trifluoroethyl formate and its three (13)C
      isotopologues have been measured with a molecular-beam-based, chirped-pulsed
      Fourier transform microwave spectrometer in combination with a conventional Balle
      Flygare-type instrument up to 18 GHz. Although ab initio calculations predict the
      presence of two low-energy conformers (analogous to the trans and gauche forms of
      ethyl formate), the trans isomer was the only stable conformer observed. The r(s)
      geometry of the molecular main carbon frame was precisely derived based on a
      coplanar heavy-atom backbone of this conformer. ESPs of the two lowest energy
      conformers were calculated to obtain information about the role of through-space
      effects on their structures and relative stability.

PMID- 21732616
TI  - Highly enantioslective synthesis of multisubstituted polyfunctional
      dihydropyrrole via an organocatalytic tandem Michael/cyclization sequence.
AB  - A unique approach to asymmetric synthesis of various optically pure
      multisubstituted 2,3-dihydropyrroles catalyzed by a novel rosin-derived tertiary
      amine-thiourea via a tandem Michael/cyclization sequence with high yield (up to
      97%) and good to excellent enantioselectivities (up to 97% ee) is present. This
      strategy provides an efficient and convenient method to access enantioenrich
      nitrogen heterocycles.

PMID- 21732617
TI  - Utilizing the adaptive polyoxometalate [As2W19O67(H2O)](14-) to support a
      polynuclear lanthanoid-based single-molecule magnet.
AB  - Five members of a new family of polyoxometalate (POM)-ligated tetranuclear rare
      earth metal complexes have been synthesized and characterized. These compounds
      have the general formula
      (HDABCO)(8)H(5)Li(8)[Ln(4)As(5)W(40)O(144)(H(2)O)(10)(gly)(2)].25H(2)O [Ln = Gd
      (1), Tb (2), Dy (3), Ho (4) and Y = (5), HDABCO = monoprotonated 1,4
      diazabicyclooctane, gly = glycine] and were synthesized from the preformed POM
      precursor [As(2)W(19)O(67)(H(2)O)](14-). The structure is comprised of two
      {As(2)W(19)O(68)} building blocks linked by a unit containing four rare earth
      ions and two additional tungsten centers, with the two glycine ligands playing a
      key bridging role. Two crystallographically distinct rare earth ions are present
      in each complex, both of which possess axially compressed, approximate square
      antiprismatic coordination geometry. The variable-temperature magnetic
      susceptibility profiles for 2-4 are dominated by population/depopulation of the
      M(J) sublevels of the relevant ground terms, and fitting of the data has afforded
      the ligand field parameters in each case, from which the energies of the M(J)
      sublevels can be calculated. Alternating current magnetic susceptibility data
      have revealed the onset of slow magnetic relaxation for 3, with the energy
      barrier to magnetization reversal determined to be 3.9(1) K. As for other
      lanthanoid complexes that display slow magnetic relaxation, this energy barrier
      is due to the splitting of the M(J) sublevels of the Dy(3+) ions such that the
      ground sublevel has a relatively large |M(J)| value, thereby affording Ising-type
      magnetic anisotropy. This complex is thus the first POM-supported polynuclear
      lanthanoid-based SMM. Simulation of the W-band EPR spectrum of 1 has afforded the
      spin Hamiltonian parameters for this species, while the X-band EPR spectrum of 3
      indicates the presence of a non-negligible fourth-order transverse component of
      the anisotropy, which is responsible for the small effective energy barrier
      observed for 3 and the absence of slow magnetic relaxation for 4.

PMID- 21732618
TI  - Correlated optical measurements and plasmon mapping of silver nanorods.
AB  - Plasmonics is a rapidly growing field, yet imaging of the plasmonic modes in
      complex nanoscale architectures is extremely challenging. Here we obtain spatial
      maps of the localized surface plasmon modes of high-aspect-ratio silver nanorods
      using electron energy loss spectroscopy (EELS) and correlate to optical data and
      classical electrodynamics calculations from the exact same particles. EELS
      mapping is thus demonstrated to be an invaluable technique for elucidating
      complex and overlapping plasmon modes.

PMID- 21732619
TI  - Charged nucleobases and their potential for RNA catalysis.
AB  - Catalysis in living cells is carried out by both proteins and RNA. Protein
      enzymes have been known for over 200 years, but RNA enzymes, or "ribozymes", were
      discovered only 30 years ago. Developing insight into RNA enzyme mechanisms is
      invaluable for better understanding both extant biological catalysis as well as
      the primitive catalysis envisioned in an early RNA-catalyzed life. Natural
      ribozymes include large RNAs such as the group I and II introns; small RNAs such
      as the hepatitis delta virus and the hairpin, hammerhead, VS, and glmS ribozymes;
      and the RNA portion of the ribosome and spliceosome. RNA enzymes use many of the
      same catalytic strategies as protein enzymes, but do so with much simpler side
      chains. Among these strategies are metal ion, general acid-base, and
      electrostatic catalysis. In this Account, we examine evidence for participation
      of charged nucleobases in RNA catalysis. Our overall approach is to integrate
      direct measurements on catalytic RNAs with thermodynamic studies on
      oligonucleotide model systems.  The charged amino acids make critical
      contributions to the mechanisms of nearly all protein enzymes. Ionized
      nucleobases should be critical for RNA catalysis as well. Indeed, charged
      nucleobases have been implicated in RNA catalysis as general acid-bases and
      oxyanion holes. We provide an overview of ribozyme studies involving nucleobase
      catalysis and the complications involved in developing these mechanisms. We also
      consider driving forces for perturbation of the pK(a) values of the bases.
      Mechanisms for pK(a) values shifting toward neutrality involve electrostatic
      stabilization and the addition of hydrogen bonding. Both mechanisms couple
      protonation with RNA folding, which we treat with a thermodynamic formalism and
      conceptual models. Furthermore, ribozyme reaction mechanisms can be multichannel,
      which demonstrates the versatility of ribozymes but makes analysis of
      experimental data challenging.  We examine advances in measuring and analyzing
      perturbed pK(a) values in RNA. Raman crystallography and fluorescence
      spectroscopy have been especially important for pK(a) measurement. These methods
      reveal pK(a) values for the nucleobases A or C equal to or greater than
      neutrality, conferring potential histidine- and lysine/arginine-like behavior on
      them. Structural support for ionization of the nucleobases also exists: an
      analysis of RNA structures in the databases conducted herein suggests that
      charging of the bases is neither especially uncommon nor difficult to achieve
      under cellular conditions. Our major conclusions are that cationic and anionic
      charge states of the nucleobases occur in RNA enzymes and that these states make
      important catalytic contributions to ribozyme activity. We conclude by
      considering outstanding questions and possible experimental and theoretical
      approaches for further advances.

PMID- 21732620
TI  - Reversible phase transitions within self-assembled fibrillar networks of (R)-18
      (n-alkylamino)octadecan-7-ols in their carbon tetrachloride gels.
AB  - The CCl(4) gel phases of a series of low-molecular-mass organogelators, (R)-18-(n
      alkylamino)octadecan-7-ols (HSN-n, where n = 0-5, 18 is the alkyl chain length),
      appear to be unprecedented in that the fibrillar networks of some of the
      homologues undergo thermally reversible, gel-to-gel phase transitions, and some
      of those transitions are evident as opaque-transparent changes in the appearance
      of the samples. The gels have been examined at different concentrations and
      temperatures by a wide variety of spectroscopic, diffraction, thermal, and
      rheological techniques. Analyses of those data and data from the neat gelators
      have led to an understanding of the source of the gel-to-gel transitions. IR and
      SANS data implicate the expulsion (on heating the lower-temperature gel) or the
      inclusion (on cooling the higher-temperature gel) of molecules of CCl(4) that are
      interspersed between fibers in bundles. However, the root cause of the
      transitions is a consequence of changes in the molecular packing of the HSN-n
      within the fibers. This study offers opportunities to design new gelators that
      are capable of behaving in multiple fashions without entering the sol/solution
      phase, and it identifies a heretofore unknown transformation of organogels.

PMID- 21732621
TI  - Selective extraction of large-diameter single-wall carbon nanotubes with specific
      chiral indices by poly(9,9-dioctylfluorene-alt-benzothiadiazole).
AB  - Semiconducting single-wall carbon nanotubes (SWCNTs) having large diameters (d(t)
      > 1.3 nm) are successfully extracted in toluene by fluorene-based polymers. In
      particular, poly(9,9-dioctylfluorene-alt-benzothiadiazole) shows excellent
      selectivity for (15,4) SWCNTs. Although the importance of structural matching
      between the fluorene backbone and the tube surface has already been discussed,
      the present photoluminescence studies reveal that matching the energy levels
      between fluorene-based polymers and SWCNTs is crucial for selective nanotube
      extractions.

PMID- 21732622
TI  - Analgesic effects and mechanisms of anti-inflammation of taraxeren-3-one from
      Diospyros maritima in mice.
AB  - This study investigated the analgesic effects of taraxeren-3-one, which is an
      ingredient from Diospyros maritima (DM), using the models of acetic acid-induced
      writhing response and the formalin test, and its anti-inflammatory effects using
      the model of lambda-carrageenan (Carr)-induced paw edema. Treatment of male ICR
      mice with taraxeren-3-one inhibited the numbers of writhing response and formalin
      induced pain in the late phase, significantly. In the anti-inflammatory test,
      taraxeren-3-one decreased paw edema at 4 and 5 h after Carr administration and
      increased the activities of superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx), and glutathione (GSH) in the liver tissue at 5 h
      after Carr injection. Taraxeren-3-one affects malondialdehyde (MDA), nitric oxide
      (NO), and tumor necrosis factor-alpha (TNF-alpha) levels from both the edema paw
      and serum at 5 h after Carr injection. Western blotting revealed that taraxeren-3
      one decreased Carr-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX
      2) expressions. These anti-inflammatory mechanisms of taraxeren-3-one might be
      related to the decrease in the level of MDA in the edema paw via increasing the
      activities of SOD, CAT, GPx, and GSH in the liver. Also, taraxeren-3-one could
      affect the production of NO and TNF-alpha and, therefore, affect the anti
      inflammatory effects.

PMID- 21732623
TI  - ALD functionalized nanoporous gold: thermal stability, mechanical properties, and
      catalytic activity.
AB  - Nanoporous metals have many technologically promising applications, but their
      tendency to coarsen limits their long-term stability and excludes high
      temperature applications. Here, we demonstrate that atomic layer deposition (ALD)
      can be used to stabilize and functionalize nanoporous metals. Specifically, we
      studied the effect of nanometer-thick alumina and titania ALD films on thermal
      stability, mechanical properties, and catalytic activity of nanoporous gold (np
      Au). Our results demonstrate that even only 1 nm thick oxide films can stabilize
      the nanoscale morphology of np-Au up to 1,000 degrees C, while simultaneously
      making the material stronger and stiffer. The catalytic activity of np-Au can be
      drastically increased by TiO(2) ALD coatings. Our results open the door to high
      temperature sensor, actuator, and catalysis applications and functionalized
      electrodes for energy storage and harvesting applications.

PMID- 21732624
TI  - A small-molecule screening strategy to identify suppressors of statin myopathy.
AB  - The reduction of plasma low-density lipoprotein levels by HMG-CoA reductase
      inhibitors, or statins, has had a revolutionary impact in medicine, but muscle
      related side effects remain a dose-limiting toxicity in many patients. We
      describe a chemical epistasis approach that can be useful in refining the
      mechanism of statin muscle toxicity, as well as in screening for agents that
      suppress muscle toxicity while preserving the ability of statins to increase the
      expression of the low-density lipoprotein receptor. Using this approach, we
      identified one compound that attenuates the muscle side effects in both cellular
      and animal models of statin toxicity, likely by influencing Rab prenylation. Our
      proof-of-concept screen lays the foundation for truly high-throughput screens
      that could help lead to the development of clinically useful adjuvants that can
      one day be co-administered with statins.

PMID- 21732625
TI  - Switchable ternary nanoporous supramolecular network on photo-regulation.
AB  - Controlled regulation of the switchable behavior of the supramolecular network is
      central to the potential application in the molecular scale nanodevices. In this
      work, it is reported that the reversible accommodation of the guest molecules in
      the nanoporous supramolecular network can be regulated by the UV/visible light.
      The nanoporous complex template of TCDB/4NN-Macrocycle(trans,trans,trans,trans)
      with photosensitive units is well-defined. After the UV irradiation, the template
      can be switched on to encapsulate coronene molecules due to the formation of a
      new photoisomer(trans,cis,trans,cis) and switched off to expel coronene from the
      inner cavities under the visible light. The photoregulated switchable
      multicomponent supramolecular guest-host network provides a novel strategy for
      fabricating the functional nanodevices at the molecular scale.

PMID- 21732626
TI  - Synthesis and in vitro biological evaluation of carbonyl group-containing
      analogues for sigma1 receptors.
AB  - To identify the ligands for sigma(1) receptors that are potent and selective,
      analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular
      acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues
      synthesized and tested, 5 displayed very high affinity for sigma(1) (K(i) = 0.48
      4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors
      (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a,
      14b, 14c, and 14e) showed very low affinity for VAChT (K(i) > 290 nM), and the
      fifth compound (14g) showed moderate affinity for VAChT (K(i) = 44.2 nM). The
      compound [1'-(4-fluorobenzyl)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4
      fluorophenyl)methanone (14a) displayed very high affinity and selectivity for
      sigma(1) receptor (K(i) = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these
      most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with
      fluorine-18 or carbon-11, which will allow further evaluation of their properties
      as PET probes for imaging sigma(1) receptor in vivo.

PMID- 21732627
TI  - Hetero-Diels-Alder reaction of phosphinyl and phosphonyl nitroso alkenes with
      conjugated dienes: an aza-Cope rearrangement.
AB  - Phosphorylated nitroso alkenes react with cyclic dienes such as cyclopentadiene
      or cyclohexadiene to afford hetero Diels-Alder-type cycloadducts where the
      nitroso alkene participates as dienophile component and the cyclic olefin acts as
      the 4pi-electron (diene) system. Subsequent aza-Cope rearrangement affords highly
      functionalized 5,6-dihydro-4H-1,2-oxazines. Conversely, the reaction of TMS
      substituted cyclopentadiene (dienophile) with nitroso alkenes as heterodienes
      leads directly to bicyclic 1,2-oxazines. Theoretical studies are in agreement
      with the experimental results and with the new aza-Cope rearrangement proposed.

PMID- 21732628
TI  - Thermal phase behavior of DMPG bilayers in aqueous dispersions as revealed by 2H-
      and 31P-NMR.
AB  - The synthetic lipid 1,2-dimyristoyl-sn-3-phosphoglycerol (DMPG), when dispersed
      in water/NaCl exhibits a complex phase behavior caused by its almost unlimited
      swelling in excess water. Using deuterium ((2)H)- and phosphorus ((31)P)-NMR we
      have studied the molecular properties of DMPG/water/NaCl dispersions as a
      function of lipid and NaCl concentration. We have measured the order profile of
      the hydrophobic part of the lipid bilayer with deuterated DMPG while the
      orientation of the phosphoglycerol headgroup was deduced from the (31)P NMR
      chemical shielding anisotropy. At temperatures >30  degrees C we observe well
      resolved (2)H- and (31)P NMR spectra not much different from other liquid
      crystalline bilayers. From the order profiles it is possible to deduce the
      average length of the flexible fatty acyl chain. Unusual spectra are obtained in
      the temperature interval of 20-25  degrees C, indicating one or several phase
      transitions. The most dramatic changes are seen at low lipid concentration and
      low ionic strength. Under these conditions and at 25  degrees C, the
      phosphoglycerol headgroup rotates into the hydrocarbon layer and the hydrocarbon
      chains show larger flexing motions than at higher temperatures. The orientation
      of the phosphoglycerol headgroup depends on the bilayer surface charge and
      correlates with the degree of dissociation of DMPG-Na(+). The larger the negative
      surface charge, the more the headgroup rotates toward the nonpolar region.

PMID- 21732629
TI  - Multicolor, one- and two-photon imaging of enzymatic activities in live cells
      with fluorescently Quenched Activity-Based Probes (qABPs).
AB  - Fluorescence imaging provides an indispensable way to locate and monitor
      biological targets within complex and dynamic intracellular environments. Of the
      various imaging agents currently available, small molecule-based probes provide a
      powerful tool for live cell imaging, primarily due to their desirable properties,
      including cell permeability (as a result of their smaller sizes), chemical
      tractability (e.g., different molecular structures/designs can be installed), and
      amenability to imaging a wide variety of biological events. With a few
      exceptions, most existing small molecule probes are however not suitable for in
      vivo bioimaging experiments in which high-resolution studies of enzyme activity
      and localization are necessary. In this article, we reported a new class of
      fluorescently Quenched Activity-Based Probes (qABPs) which are highly modular,
      and can sensitively image (through multiple enzyme turnovers leading to
      fluorescence signal amplification) different types of enzyme activities in live
      mammalian cells with good spatial and temporal resolution. We have also
      incorporated two-photon dyes into our modular probe design, enabling for the
      first time activity-based, fluorogenic two-photon imaging of enzyme activities.
      This, hence, expands the repertoire of 'smart', responsive probes currently
      available for live cell bioimaging experiments.

PMID- 21732630
TI  - A synthetic antimicrobial peptidomimetic (LTX 109): stereochemical impact on
      membrane disruption.
AB  - LTX 109 is a synthetic antimicrobial peptidomimetic (SAMP) currently in clinical
      phase II trials for topical treatment of infections of multiresistant bacterial
      strains. All possible eight stereoisomers of the peptidomimetic have been
      synthesized and tested for antimicrobial effect, hemolysis, and hydrophobicity,
      revealing a strong and unusual dependence on the stereochemistry for a molecule
      proposed to act on a general membrane mechanism. The three-dimensional structures
      were assessed using nuclear magnetic resonance spectroscopy (NMR) and molecular
      dynamics (MD) simulations in aqueous solution and in phospholipid bilayers. The
      solution structures of the most active stereoisomers are perfectly preorganized
      for insertion into the membrane, whereas the less active isomers need to pay an
      energy penalty in order to enter the lipid bilayer. This effect is also found to
      be reinforced by a significantly improved water solubility of the less active
      isomers due to a guanidyl-pi stacking that helps to solvate the hydrophobic
      surfaces.

PMID- 21732631
TI  - Nitrogen-containing organic compounds and oligomers in secondary organic aerosol
      formed by photooxidation of isoprene.
AB  - Electrospray ionization high-resolution mass spectrometry (ESI HR-MS) was used to
      probe molecular structures of oligomers in secondary organic aerosol (SOA)
      generated in laboratory experiments on isoprene photooxidation at low- and high
      NO(x) conditions. Approximately 80-90% of the observed products are oligomers and
      up to 33% by number are nitrogen-containing organic compounds (NOC). We observe
      oligomers with maximum 8 monomer units in length. Tandem mass spectrometry
      (MS(n)) confirms NOC compounds are organic nitrates and elucidates plausible
      chemical building blocks contributing to oligomer formation. Most organic
      nitrates are comprised of methylglyceric acid units. Other important
      multifunctional C(2)-C(5) monomer units are identified including methylglyoxal,
      hydroxyacetone, hydroxyacetic acid, and glycolaldehyde. Although the molar
      fraction of NOC in the high-NO(x) SOA is high, the majority of the NOC oligomers
      contain only one nitrate moiety resulting in a low average N:C ratio of 0.019.
      Average O:C ratios of the detected SOA compounds are 0.54 under the low-NO(x)
      conditions and 0.83 under the high-NO(x) conditions. Our results underscore the
      importance of isoprene photooxidation as a source of NOC in organic particulate
      matter.

PMID- 21732632
TI  - Dominant Intermediate Charcot-Marie-Tooth disorder is not due to a catalytic
      defect in tyrosyl-tRNA synthetase.
AB  - Charcot-Marie-Tooth disorder (CMT) is the most common inherited peripheral
      neuropathy, afflicting 1 in every 2500 Americans. One form of this disease,
      Dominant Intermediate Charcot-Marie-Tooth disorder type C (DI-CMTC), is due to
      mutation of the gene encoding the cytoplasmic tyrosyl-tRNA synthetase (TyrRS).
      Three different TyrRS variants have been found to give rise to DI-CMTC: replacing
      glycine at position 41 by arginine (G41R), replacing glutamic acid at position
      196 by lysine (E196K), and deleting amino acids 153-156 (Delta(153-156)). To test
      the hypothesis that DI-CMTC is due to a defect in the ability of tyrosyl-tRNA
      synthetase to catalyze the aminoacylation of tRNA(Tyr), we have expressed each of
      these variants as recombinant proteins and used single turnover kinetics to
      characterize their abilities to catalyze the activation of tyrosine and its
      subsequent transfer to the 3' end of tRNA(Tyr). Two of the variants, G41R and
      Delta(153-156), display a substantial decrease in their ability to bind tyrosine
      (>100-fold). In contrast, the E196K substitution does not significantly affect
      the kinetics for formation of the tyrosyl-adenylate intermediate and actually
      increases the rate at which the tyrosyl moiety is transferred to tRNA(Tyr). The
      observation that the E196K substitution does not decrease the rate of catalysis
      indicates that DI-CMTC is not due to a catalytic defect in tyrosyl-tRNA
      synthetase.

PMID- 21732633
TI  - Urinary bisphenol A concentrations and their implications for human exposure in
      several Asian countries.
AB  - Bisphenol A (BPA) is an industrial chemical used in the manufacture of
      polycarbonate plastics and epoxy resins. Due to the potential of this compound to
      disrupt normal endocrinal functions, concerns over human exposure to BPA have
      been raised. Although several studies have reported human exposure to BPA in
      Western nations, little is known about exposure in Asian countries. In this
      study, we determined total urinary BPA concentrations (free plus conjugated) in
      296 urine samples (male/female: 153/143) collected from the general population in
      seven Asian countries, China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam,
      using high-performance liquid chromatography (HPLC) tandem mass spectrometry
      (MS/MS). On the basis of urinary BPA concentrations, we estimated the total daily
      intake. The results indicated that BPA was detected in 94.3% of the samples
      analyzed, at concentrations ranging from <0.1 to 30.1 ng/mL. The geometric mean
      concentration of BPA for the entire sample set from seven countries was 1.20
      ng/mL. The highest concentration of BPA was found in samples from Kuwait (median:
      3.05 ng/mL, 2.45 MUg/g creatinine), followed by Korea (2.17 ng/mL, 2.40 MUg/g),
      India (1.71 ng/mL, 2.09 MUg/g), Vietnam (1.18 ng/mL, 1.15 MUg/g), China (1.10
      ng/mL, 1.38 MUg/g), Malaysia (1.06 ng/mL, 2.31 MUg/g), and Japan (0.95 ng/mL,
      0.58 MUg/g). Among the five age groups studied (<= 19, 20-29, 30-39, 40-49, and
      >= 50 years), the highest median concentration of BPA was found in urine samples
      from the age group of <= 19 years. There was no significant difference in BPA
      concentrations between genders (male and female) or domicile of residence (rural
      and urban). The estimated median daily intakes of BPA for the populations in
      Kuwait, Korea, India, China, Vietnam, Malaysia, and Japan were 5.19, 3.69, 2.90,
      2.13, 2.01, 1.80, and 1.61 MUg/day, respectively. The estimated daily intake of
      BPA in the seven Asian countries was significantly lower than the tolerable daily
      intake recommended by the U.S. Environmental Protection Agency. This is the first
      study to document the occurrence of and human exposure to BPA in several Asian
      countries.

PMID- 21732634
TI  - Ruthenium-catalyzed homo Diels-Alder [2 + 2 + 2] cycloadditions of alkynyl
      phosphonates with bicyclo[2.2.1]hepta-2,5-diene.
AB  - Ruthenium-catalyzed homo Diels-Alder [2 + 2 + 2] cycloadditions between alkynyl
      phosphonates and bicyclo[2.2.1]hepta-2,5-diene were studied. The observed
      reactivity was found to be dependent on the presence of the phosphonate moiety.
      The Ru-catalyzed cycloaddition was compatible with a variety of aromatic and
      aliphatic substituted alkynyl phosphonates, providing the corresponding
      phosphonate substituted deltacyclenes in low to good yields (up to 88%).

PMID- 21732635
TI  - Should we consider using liquid fluoride thorium reactors for power generation?

PMID- 21732636
TI  - Toxicity of carbon dioxide: a review.
AB  - The toxicity of carbon dioxide has been established for close to a century. A
      number of animal experiments have explored both acute and long-term toxicity with
      respect to the lungs, the cardiovascular system, and the bladder, showing
      inflammatory and possible carcinogenic effects. Carbon dioxide also induces
      multiple fetal malformations and probably reduces fertility in animals. The aim
      of the review is to recapitulate the physiological and metabolic mechanisms
      resulting from CO(2) inhalation. As smokers are exposed to a high level of carbon
      dioxide (13%) that is about 350 times the level in normal air, we propose the
      hypothesis that carbon dioxide plays a major role in the long term toxicity of
      tobacco smoke.

PMID- 21732637
TI  - Ion-tuned DNA/Ag fluorescent nanoclusters as versatile logic device.
AB  - A novel kind of versatile logic device has been constructed utilizing ion-tuned
      DNA/Ag fluorescent nanoclusters, with K(+) and H(+) as two inputs. A well-chosen
      hairpin DNA with a poly-C loop serves as the template for synthesizing two
      species of Ag nanoclusters. Several G-tracts and C-tracts on its two terminals
      enable the hairpin DNA to convert into the G-quadruplex and/or i-motif structures
      upon input of K(+) and H(+). Such a structural change remarkably influences the
      spectral behaviors of Ag nanoclusters. In particular, different species of Ag
      nanoclusters have distinct fluorescence responses to the input of K(+) and H(+).
      These unique features of DNA/Ag nanoclusters enable multiple logic operations via
      multichannel fluorescence output, indicating the versatility as a molecular logic
      device. By altering the specific sequence of the hairpin DNA, more logic gates
      can be constructed utilizing Ag nanoclusters.

PMID- 21732638
TI  - The p38 MAPK inhibitor SB203580 induces cytochrome P450 1A1 gene expression in
      murine and human hepatoma cell lines through ligand-dependent aryl hydrocarbon
      receptor activation.
AB  - We have previously shown that the p38 MAPK inhibitor SB203580 (SB) significantly
      induced Cyp1a1 gene expression at the mRNA and activity levels, whereas it
      dramatically inhibited the induction of Cyp1a1 by TCDD in murine hepatoma Hepa
      1c1c7 cells. However, the molecular mechanisms involved were not investigated
      yet. Therefore, the current study aims to examine the capacity of SB to induce
      the constitutive CYP1A1 gene expression in Hepa 1c1c7 and HepG2 cells and to
      explore the mechanisms involved. Our results showed that SB induced the Cyp1a1
      mRNA, protein, and activity levels in a concentration-dependent manner in Hepa
      1c1c7 cells. The increase in Cyp1a1 mRNA by SB was completely blocked by the
      transcriptional inhibitor, actinomycin D, implying that SB increased de novo RNA
      synthesis. In addition, the lack of Cyp1a1 induction by SB in mutant aryl
      hydrocarbon receptor (AhR)-deficient C12 cells and with cotreatment with the AhR
      antagonist, alpha-naphthoflavone, clearly suggests an AhR-dependent induction.
      This was further supported by the ability of SB to induce Cyp1a1 independent from
      its effect on MAPKs, and to bind to and activate AhR transformation and its
      subsequent binding to the xenobiotic responsive element (XRE). This is the first
      demonstration that the p38 MAPK inhibitor, SB can directly bind to and activate
      AhR-induced Cyp1a1 gene expression in an AhR-dependent manner and represents a
      novel mechanism by which SB induces this enzyme.

PMID- 21732639
TI  - A role for Dehalobacter spp. in the reductive dehalogenation of dichlorobenzenes
      and monochlorobenzene.
AB  - Previously, we demonstrated the reductive dehalogenation of dichlorobenzene (DCB)
      isomers to monochlorobenzene (MCB), and MCB to benzene in sediment microcosms
      derived from a chlorobenzene-contaminated site. In this study, enrichment
      cultures were established for each DCB isomer and each produced MCB and trace
      amounts of benzene as end products. MCB dehalogenation activity could only be
      transferred in sediment microcosms. The 1,2-DCB-dehalogenating culture was
      studied the most intensively. Whereas Dehalococcoides spp. were not detected in
      any of the microcosms or cultures, Dehalobacter spp. were detected in 16S rRNA
      gene clone libraries from 1,2-DCB enrichment cultures, and by PCR using
      Dehalobacter-specific primers in 1,3-DCB and 1,4-DCB enrichments and MCB
      dehalogenating microcosms. Quantitative PCR showed Dehalobacter 16S rRNA gene
      copies increased up to 3 orders of magnitude upon dehalogenation of DCBs or MCB,
      and that nearly all of bacterial 16S rRNA genes in a 1,2-DCB-dehalogenating
      culture belonged to Dehalobacter spp. Dehalobacter 16S rRNA genes from DCB
      enrichment cultures and MCB-dehalogenating microcosms showed considerable
      diversity, implying that 16S rRNA sequences do not predict dehalogenation-spectra
      of Dehalobacter spp. These studies support a role for Dehalobacter spp. in the
      reductive dehalogenation of DCBs and MCB, and this genus should be considered for
      its potential impact on chlorobenzene fate at contaminated sites.

PMID- 21732640
TI  - Synthesis of unsymmetrical sulfides using ethyl potassium xanthogenate and
      recyclable copper catalyst under ligand-free conditions.
AB  - The synthesis of unsymmetrical sulfides has been achieved in good to excellent
      yields with inexpensive ethyl potassium xanthogenate via cross-coupling reaction
      using recyclable CuO nanoparticles under ligand-free conditions.The copper oxide
      nanoparticles can be recovered and reused up to five cycles without loss of
      activity.

PMID- 21732641
TI  - Regioselective ring opening and isomerization reactions of 3,4-epoxyesters
      catalyzed by boron trifluoride.
AB  - Efficient ring opening of 3,4-epoxyesters with alcohols to produce 4-alkoxy-3
      hydroxyesters and their isomerization into 4-ketoesters using boron trifluoride
      as the catalyst are presented. Both transformations are simple and efficient
      methods for the synthesis of the above named synthetically useful compounds.

PMID- 21732642
TI  - Single-walled carbon nanotube/pyrenecyclodextrin nanohybrids for ultrahighly
      sensitive and selective detection of p-nitrophenol.
AB  - Electrochemical detection of p-nitrophenol (P-NP) using a highly sensitive and
      selective platform based on single-walled carbon nanotube/pyrenecyclodextrin
      (SWCNT/PyCD) nanohybrids is described for the first time. The electrochemical
      performance of the SWCNT/PyCD nanohybrid electrode was fully compared with bare
      glassy carbon, single-SWCNT, single-PyCD, and SWCNT/CD (without pyrene rings)
      electrodes. Besides the techniques of cyclic voltammetry and chronoamperometric
      transients, differential pulse voltammetry (DPV) has been used for the detection
      of P-NP without any interference from o-nitrophenol (O-NP) at the potentials of 
      0.80 and -0.67 V, respectively. The SWCNT/PyCD nanohybrid electrode is highly
      sensitive, and it shows an ultrahigh sensitivity of 18.7 MUA/MUM toward P-NP in
      contrast to the values reported previously. The detection limit (S/N = 3) of the
      SWCNT/PyCD nanohybrid electrode toward P-NP is 0.00086 MUM (0.12 ppb), which is
      well below the allowed limit in drinking water, 0.43 MUM, given by the U.S.
      Environmental Protection Agency (EPA). The analytical performance of the
      SWCNT/PyCD nanohybrid electrode toward P-NP is superior to the existing
      electrodes.

PMID- 21732643
TI  - BN white graphene with "colorful" edges: the energies and morphology.
AB  - Interfaces play a key role in low dimensional materials like graphene or its
      boron nitrogen analog, white graphene. The edge energy of hexagonal boron nitride
      (h-BN) has not been determined as its lower symmetry makes it difficult to
      separate the opposite B-rich and N-rich zigzag sides. We report unambiguous
      energy values for arbitrary edges of BN, including the dependence on the
      elemental chemical potentials of B and N species. A useful manifestation of the
      additional Gibbs degree of freedom in the binary system, this dependence offers a
      way to control the morphology of pure BN or its carbon inclusions and to engineer
      their electronic and magnetic properties.

PMID- 21732644
TI  - Synthesis of functionalized pyridazin-3(2H)-ones via selective bromine-magnesium
      exchange and lactam directed ortho C-H magnesiation.
AB  - Selective bromine-magnesium exchange on 2-benzyl-5-bromo-4-methoxypyridazin-3(2H)
      one could be achieved when MesMgBr was used as reagent. With more nucleophilic
      RMgCl species (R = Bu, i-Pr, Ph) both nucleophilic addition-elimination at C-4
      and bromine-magnesium exchange at C-5 occurred. In 2-benzyl-5-bromopyridazin
      3(2H)-one, which does not contain a substituent at C-4, addition could not be
      suppressed. Less nucleophilic Mg amides (TMPMgCl.LiCl) allowed regioselective C-H
      magnesiation at the C-4 position in such substrates, as exemplified for 2-benzyl
      5-chloro- and 2-benzyl-6-chloropyridazin-3(2H)-one. Quenching of the magnesiated
      pyridazinones with electrophiles gives access to a variety of hitherto unknown
      pyridazin-3(2H)-one derivatives.

PMID- 21732645
TI  - Achieving chemo-, regio-, and stereoselectivity in palladium-catalyzed reaction
      of gamma-borylated allylic acetates.
AB  - Three-carbon highly functionalized gamma-borylated allylic acetates underwent a
      regio- and stereocontrolled Tsuji-Trost reaction in the presence of palladium
      complexes. An ipso substitution of the acetate with complete stereoretention of
      the chiral center was achieved, leading to vinylic boronates with enantiomeric
      excesses above 99%.

PMID- 21732646
TI  - Thermodynamic and physical interactions between novel polymeric surfactants and
      lipids: toward designing stable polymer-lipid complexes.
AB  - Surfactant amphiphilic macromolecules (AMs) were complexed with a 1:1 ratio of
      1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine (DOPE), either by a coevaporation (CE) or postaddition (PA)
      method, to form AM-lipid complexes with enhanced drug delivery applications. By
      characterizing the surfactant-lipid interactions, these heterogeneous drug
      delivery systems can be better controlled and engineered for optimal therapeutic
      outcomes. In this study, the physical interactions between DOPE:DOTAP liposomes
      and AM surfactants were investigated. Langmuir film balance and isothermal
      calorimetry studies showed cooperative intermolecular interactions between pure
      lipids and AM in monolayers and high thermostability of structure formed by the
      addition of AM micelles to DOTAP:DOPE vesicles in buffer solution respectively.
      Increasing the AM weight ratio in the complexes via the CE method led to complete
      vesicle solubilization--from lamellar aggregates, to a mixture of coexisting
      vesicles and micelles, to mixed micelles. Isothermal calorimetry evaluation of AM
      lipid complexes shows that, at higher AM weight ratios, PA-produced complexes
      exhibit greater stability than complexes at lower AM weight ratios. Similar
      studies show that AM-lipid complexes produced by the CE methods display stronger
      interactions between AM-lipid components than complexes produced by the PA
      method. The results suggest that the PA method produces vesicles with AM
      molecules associated with its outer leaflet only (i.e., an AM-coated vesicle),
      while the CE method produces complexes ranging from mixed vesicles to mixed
      micelle in which the AM-lipid components are more intimately associated. These
      results will be helpful in the design of AM-lipid complexes as structurally
      defined, stable, and effective drug delivery systems.

PMID- 21732647
TI  - Highly luminescent CdSe/Cd(x)Zn(1-x)S quantum dots coated with thickness
      controlled SiO2 shell through silanization.
AB  - A silanization technique of hydrophobic quantum dots (QDs) was applied to SiO(2)
      coated CdSe/Cd(x)Zn(1-x)S QDs to precisely control the SiO(2) shell thickness and
      retain the original high photoluminescence (PL) properties of the QDs.
      Hydrophobic CdSe/Cd(x)Zn(1-x)S core-shell QDs with PL peak wavelengths of 600 and
      652 nm were prepared by a facile organic route by using oleic acid (OA) as a
      capping agent. The QDs were silanized by using partially hydrolyzed tetraethyl
      orthosilicate by replacing surface OA. These silanized QDs were subsequently
      encapsulated in a SiO(2) shell by a reverse micelles synthesis. The silanization
      plays an important role for the QDs to be coated with a homogeneous SiO(2) shell
      and retain a high PL efficiency in water. Transmission electron microscopy
      observation shows that the shells are 1-9 nm with final particle sizes of 10-25
      nm, depending on the initial QD size. In the case of short reaction time (6 h),
      the QDs were coated with a very thin SiO(2) layer because no visible SiO(2) shell
      was observed but transferred into the water phase. The silica coating does not
      change the PL peak wavelength of the QDs. The full width at half-maximum of PL
      was decreased 4 nm after coating for QDs emitting at both 600 and 652 nm. The PL
      efficiency of the SiO(2)-coated is up to 40%, mainly determined by the initial PL
      efficiency of the underlying CdSe/Cd(x)Zn(1-x)S QDs.

PMID- 21732648
TI  - Anisotropic wetting on checkerboard-patterned surfaces.
AB  - A series of surfaces with microscale checkerboard patterns consisting of
      continuous central lines and discontinuous lateral lines were fabricated. The
      surface wetting properties of these checkerboard patterns were found to be
      anisotropic. The central continuous lines were found to have a strong influence
      on the dynamic wetting properties and moving trajectories of the water droplets.
      The droplets move more easily in the direction parallel to the central continuous
      lines and less easily in the direction perpendicular to the central continuous
      lines. Meanwhile, the droplets' moving path tends to incline toward the central
      continuous lines from a tilting direction. When the microsurface was modified
      with a layer of nanowire, the surface wettability was found to be isotropic and
      superhydrophobic.

PMID- 21732649
TI  - Chlorotrimethylsilane activation of acylcyanamides for the synthesis of mono-N
      acylguanidines.
AB  - A simple and efficient one-pot method for the synthesis of monoprotected
      guanidines is presented. Treatment of an acylcyanamide with chlorotrimethylsilane
      generates a reactive N-silylcarbodiimide capable of guanylating a variety of
      amines. Typically the reaction is complete in 15 min for primary and secondary
      aliphatic amines at rt. Hindered amines and anilines are also competent
      nucleophiles but require extended reaction times.

PMID- 21732650
TI  - Synthesis of iodo-indoloazepinones in an iodine-mediated three-component domino
      reaction via a regioselective 7-endo-dig iodo-cyclization pathway.
AB  - An efficient and rapid synthetic strategy for the naturally occurring
      indoloazepinone scaffold via a three-component reaction of indole-2-carboxamides,
      1,3-disubstituted propargyl alcohols, and I(2) is described. The strategy
      involves a C-H functionalization-alkyne activation-intramolecular hydroamidation
      deprotonation domino sequence. The salient feature of this sequence is
      regioselective electrophilic 7-endo-dig iodo-cyclization during the
      intramolecular hydroamidation to afford a seven-membered azepinone ring annulated
      to the indole.

PMID- 21732651
TI  - Determination of parent and substituted polycyclic aromatic hydrocarbons in high
      fat salmon using a modified QuEChERS extraction, dispersive SPE and GC-MS.
AB  - A fast and easy modified QuEChERS (quick, easy, cheap, rugged and safe)
      extraction method has been developed and validated for determination of 33 parent
      and substituted polycyclic aromatic hydrocarbons (PAHs) in high-fat smoked salmon
      that greatly enhances analyte recovery compared to traditional QuEChERS
      procedures. Sample processing includes extraction of PAHs into a solution of
      ethyl acetate, acetone and isooctane followed by cleanup with dispersive SPE and
      analysis by GC-MS in SIM mode. Method performance was assessed in spike recovery
      experiments (500 MUg/g wet weight) in three commercially available smoked salmon
      with 3-11% fat. Recoveries of some 2-, 3- and 5-ring PAHs were improved 50-200%
      over traditional methods, while average recovery across all PAHs was improved
      67%. Method precision was good with replicate extractions typically yielding
      relative standard deviations <10%, and detection limits were in the low ng/g
      range. With this method, a single analyst could extract and clean up >=60 samples
      for PAH analysis in an 8 h work day.

PMID- 21732652
TI  - pi-Extended and six-coordinate iron(II) complexes: structures, magnetic
      properties, and the electrochemical synthesis of a conducting iron(II)
      metallopolymer.
AB  - Herein, we describe the preparation of three new bidentate pi-extended
      derivatives of the ligand N-phenyl-2-pyridinalimine (ppi) containing a 3-thienyl
      (4) substituent at position 4 of the aniline ring or 2-thienyl (6) or phenyl (2)
      substituents at each of the 2,5 positions of the aniline rings. Three iron(2+)
      complexes (7-9) containing these ligands were prepared by combining two
      equivalents each of 2, 4, or 6 with Fe(NCS)(2), and the resulting neutral, six
      coordinate complexes were fully characterized, including with single crystal X
      ray diffraction experiments in the case of complexes 7 and 9. Variable
      temperature magnetic susceptibility and Mossbauer experiments confirm the
      presence of spin-crossover in complexes 7 and 8, and the unusual solid state
      variable temperature magnetic properties of complex 9 likely result from crystal
      packing forces. Electropolymerization of the 2,5-dithienyl-substituted complex
      (9) produces a conducting and electrochromic metallopolymer film (poly-9).

PMID- 21732653
TI  - Ribonuclease a: revealing structure-function relationships with semisynthesis.

PMID- 21732654
TI  - Thickness dependence of plasmonic charge carrier generation in ultrathin a-Si:H
      layers for solar cells.
AB  - Nanocomposite layers of Ag nanoparticles and a-Si:H film constitute attractive
      candidates for the realization of ultrathin "two-dimensional" plasmonic solar
      cells, with an ideal 18% efficiency predicted for an average layer thickness of
      only 20 nm. By combining optical spectroscopy with photoconductivity
      measurements, we here characterize different contributions to the light
      absorption and charge carrier generation in such nanocomposites. We focus in
      particular on the important role of the absorber layer thickness for these
      processes, by studying a range of a-Si:H thicknesses from 9 to 67 nm. Through
      detailed comparison with numerical calculations by the finite element method,
      observed experimental features are connected to specific resonance modes and
      charge carrier generation mechanisms. The influence of dipolar and quadrupolar
      near-field distributions are evaluated with respect to different figures of merit
      for plasmonic solar cells. We briefly discuss how the present findings may be
      implemented in practical solar cell configurations.

PMID- 21732655
TI  - Comment on "Comparative assessment of life cycle assessment methods used for
      personal computers".

PMID- 21732656
TI  - Metal-free oxyaminations of alkenes using hydroxamic acids.
AB  - A radical-mediated approach to metal-free alkene oxyamination is described. This
      method capitalizes on the unique reactivity of the amidoxyl radical in alkene
      additions to furnish a general difunctionalization using simple diisopropyl
      azodicarboxylate (DIAD) as a radical trap. This protocol capitalizes on the
      intramolecular nature of the process, providing single regioisomers in all cases.
      Difunctionalizations of cyclic alkenes provide trans oxyamination products
      inaccessible using current methods with high levels of stereoselectivity,
      complementing cis-selective oxyamination processes.

PMID- 21732657
TI  - Photolysis of (3-methyl-2H-azirin-2-yl)-phenylmethanone: direct detection of a
      triplet vinylnitrene intermediate.
AB  - The photoreactivity of (3-methyl-2H-azirin-2-yl)-phenylmethanone, 1, is
      wavelength-dependent (Singh et al. J. Am. Chem. Soc. 1972, 94, 1199-1206).
      Irradiation at short wavelengths yields 2P, whereas longer wavelengths produce
      3P. Laser flash photolysis of 1 in acetonitrile using a 355 nm laser forms its
      triplet ketone (T(1K), broad absorption with lambda(max) ~ 390-410 nm, tau ~ 90
      ns), which cleaves and yields triplet vinylnitrene 3 (broad absorption with
      lambda(max) ~ 380-400 nm, tau = 2 MUs). Calculations (B3LYP/6-31+G(d)) reveal
      that T(1K) of 1 is located 67 kcal/mol above its ground state (S(0)) and has a
      long C-N bond (1.58 A), and the calculated transition state to form 3 is only 1
      kcal/mol higher in energy than T(1K) of 1. The calculations show that 3 has
      significant 1,3-carbon iminyl biradical character, which explains why 3 reacts
      efficiently with oxygen and decays by intersystem crossing to the singlet
      surface. Photolysis of 1 in argon matrixes at 14 K produced ketene imine 7, which
      presumably is formed from 3 intersystem crossing to 7. In comparison, photolysis
      of 1 in methanol with a 266 nm laser produces mainly ylide 2 (lambda(max) ~ 380
      nm, tau ~ 6 MUs, acetonitrile), which decays to form 2P. Ylide 2 is formed via
      singlet reactivity of 1, and calculations show that the first singlet excited
      state of the azirine chromophore (S(1A)) is located 113 kcal/mol above its S(0)
      and that the singlet excited state of the ketone (S(1K)) is 85 kcal/mol.
      Furthermore, the transition state for cleaving the C-C bond in 1 to form 2 is
      located 49 kcal/mol above the S(0) of 1. Thus, we theorize that internal
      conversion of S(1A) to a vibrationally hot S(0) of 1 forms 2, whereas intersystem
      crossing from S(1K) to T(1K) results in 3.

PMID- 21732658
TI  - Difference of coordination between alkali- and alkaline-earth-metal ions to a
      symmetrical alpha,alpha',delta,delta'-tetramethylcucurbit[6]uril.
AB  - To explore differences in coordination between alkali- and alkaline-earth-metal
      ions and cucurbit[n]urils, a water-soluble alpha,alpha',delta,delta'
      tetramethylcucurbit[6]uril (TMeQ[6]) was used to synthesize a series of complexes
      and their supramolecular assemblies, based on the coordination of TMeQ[6] with
      alkali- and alkaline-earth-metal ions. The complexes and corresponding
      supramolecular assemblies were structurally characterized by single-crystal X-ray
      diffraction. Unlike cucurbituril (Q[6]), which formed the metal-Q[6] polymers
      based on the direct coordination of carbonyl oxygen atoms to the alkali-metal
      ions, TMeQ[6] formed metal-TMeQ[6] polymers based on the direct coordination of
      carbonyl oxygen atoms with the alkaline-earth-metal ions rather than the alkali
      metal ions.

PMID- 21732659
TI  - Enantioselective N-heterocyclic carbene-catalyzed Michael addition to alpha,beta
      unsaturated aldehydes by redox oxidation.
AB  - Enantioselective N-heterocyclic carbene-catalyzed Michael addition reactions to
      alpha,beta-unsaturated aldehydes by redox oxidation were realized. With 10 mol %
      of camphor-derived triazolium salt D, 15 mol % of DBU, 5 mol % of NaBF(4), and
      100 mol % of quinone oxidant, the reactions of various dicarbonyl compounds with
      alpha,beta-unsaturated aldehydes led to 3,4-dihydro-alpha-pyrones in good yields
      and excellent ee's.

PMID- 21732660
TI  - Monoalkylation of acetonitrile by primary alcohols catalyzed by iridium
      complexes.
AB  - The monoalkylation of acetonitrile by primary alcohols was achieved in a one-pot
      sequence in the presence of iridium catalysts. A diversity of nitriles has been
      obtained from aryl- and alkyl-methanols in excellent yield.

PMID- 21732661
TI  - Synthesis of the tricyclic core of labiatin A and australin A.
AB  - A concise synthesis of the tricyclic core of the marine diterpene natural
      products labiatin A and australin A has been accomplished. The key ring-forming
      transformation is a cascade reaction comprising generation of a copper carbenoid
      from a diazo ketone, intramolecular reaction of the carbenoid with a cyclic
      ether, and rearrangement of the resulting free oxonium ylide or its metal-bound
      equivalent with ring expansion of the original cyclic ether.

PMID- 21732662
TI  - Substituent effects in synthetic lectins--exploring the role of CH-pi
      interactions in carbohydrate recognition.
AB  - Contacts between aromatic surfaces and saccharide CH groups are common motifs in
      natural carbohydrate recognition. These CH-pi interactions are modeled in
      "synthetic lectins" which employ oligophenyl units as apolar surfaces. Here we
      report the synthesis and study of new synthetic lectins with fluoro- and hydroxy
      substituted biphenyl units, designed to explore the role of pi-electron density
      in carbohydrate CH-pi interactions. We find evidence that recognition can be
      moderated through electronic effects but that other factors such as cavity
      hydration are also important and sometimes predominant in determining binding
      strengths.

PMID- 21732663
TI  - Facile Sc(OTf)3-catalyzed generation and successive aromatization of
      isobenzofuran from o-dicarbonylbenzenes.
AB  - Isobenzofuran can be prepared from o-phthalaldehyde using hydrosilane. The formed
      isobenzofuran is trapped by an alkene via a Diels-Alder reaction. Further
      dehydration proceeds to furnish the conjugated aromatic compound. This multistep
      reaction was promoted by catalytic amounts of Sc(OTf)(3).

PMID- 21732664
TI  - Detection of environmentally persistent free radicals at a superfund wood
      treating site.
AB  - Environmentally persistent free radicals (EPFRs) have previously been observed in
      association with combustion-generated particles and airborne PM(2.5) (particulate
      matter, d < 2.5um). The purpose of this study was to determine if similar
      radicals were present in soils and sediments at Superfund sites. The site was a
      former wood treating facility containing pentachlorophenol (PCP) as a major
      contaminant. Both contaminated and noncontaminated (just outside the contaminated
      area) soil samples were collected. The samples were subjected to the conventional
      humic substances (HS) extraction procedure. Electron paramagnetic resonance (EPR)
      spectroscopy was used to measure the EPFR concentrations and determine their
      structure for each sample fraction. Analyses revealed a ~30* higher EPFR
      concentration in the PCP contaminated soils (20.2 * 10(17) spins/g) than in the
      noncontaminated soil (0.7 * 10(17) spins/g). Almost 90% of the EPFR signal
      originated from the minerals/clays/humins fraction. GC-MS analyses revealed ~6500
      ppm of PCP in the contaminated soil samples and none detected in the background
      samples. Inductively coupled plasma-atomic emission spectrophotometry (ICP-AES)
      analyses revealed ~7* higher concentrations of redox-active transition metals, in
      the contaminated soils than the noncontaminated soil. Vapor phase and liquid
      phase dosing of the clays/minerals/humins fraction of the soil with PCP resulted
      in an EPR signal identical to that observed in the contaminated soil, strongly
      suggesting the observed EPFR is pentachlorophenoxyl radical. Chemisorption and
      electron transfer from PCP to transition metals and other electron sinks in the
      soil are proposed to be responsible for EPFR formation.

PMID- 21732665
TI  - Deformation and breakup of micro- and nanoparticle stabilized droplets in
      microfluidic extensional flows.
AB  - Using a microfluidic flow-focusing device, monodisperse water droplets in oil
      were generated and their interface populated by either 1 MUm or 500 nm amine
      modified silica particles suspended in the water phase. The deformation and
      breakup of these Pickering droplets were studied in both pure extensional flow
      and combined extensional and shear flow at various capillary numbers using a
      microfluidic hyperbolic contraction. The shear resulted from droplet confinement
      and increased with droplet size and position along the hyperbolic contraction.
      Droplet deformation was found to increase with increasing confinement and
      capillary number. At low confinements and low capillary numbers, the droplet
      deformation followed the predictions of theory. For fully confined droplets,
      where the interface was populated by 1 MUm silica particles, the droplet
      deformation increased precipitously and two tails were observed to form at the
      rear of the droplet. These tails were similar to those seen for surfactant
      covered droplets. At a critical capillary number, daughter droplets were observed
      to stream from these tails. Due to the elasticity of the particle-laden
      interface, these drops did not return to a spherical shape, but were observed to
      buckle. Although increases in droplet deformation were observed, no tail
      streaming occurred for the 500 nm silica particle covered droplets over the range
      of capillary numbers studied.

PMID- 21732666
TI  - A single intrathecal injection of DNA and an asymmetric cationic lipid as
      lipoplexes ameliorates experimental autoimmune encephalomyelitis.
AB  - Intrathecal delivery of gene therapeutics is a route of administration that
      overcomes several of the limitations that plague current immunosuppressive
      treatments for autoimmune diseases of the central nervous system (CNS). Here we
      report intrathecal delivery of small amounts (3 MUg) of plasmid DNA that codes
      for an immunomodulatory fusion protein, OX40-TRAIL, composed of OX40, a tumor
      necrosis factor receptor, and tumor necrosis factor related apoptosis inducing
      ligand (TRAIL). This DNA was delivered in a formulated nucleic acid-lipid complex
      (lipoplexes) with an asymmetric two-chain cationic lipid myristoyl (14:0) and
      lauroyl (12:1) rosenthal inhibitor-substituted compound (MLRI) formed from the
      tetraalkylammonium glycerol-based compound N-(1-(2,3-dioleoyloxy)-propyl-N-1-(2
      hydroxy)ethyl)-N,N-dimethyl ammonium iodide. Delivery and expression in the CNS
      of OX40-TRAIL in the mouse prior to onset of experimental autoimmune
      encephalomyelitis (EAE), an animal model for multiple sclerosis, decreased the
      severity of clinical disease. We believe this preclinical demonstration of rapid,
      widespread, and biologically therapeutic nonviral gene delivery to the CNS is
      important in further development of clinical lipid-based therapeutics for CNS
      disorders.

PMID- 21732667
TI  - Theoretical investigation of adsorption of molecular oxygen on small copper
      clusters.
AB  - Adsorption of molecular oxygen on Cu(N) (N = 2-10) clusters is investigated using
      density functional theory under the generalized gradient approximation of Perdew
      Burke-Ernzerhof. An extensive structure search is performed to identify low
      energy conformations of Cu(N)O(2) complexes. Optimal adsorption sites are
      assigned for low-energy isomers of the clusters. Among these are some new
      arrangements unidentified heretofore. Distinct size dependences are noted for the
      ground state Cu(N)O(2) complexes in stability, adsorption energy, Cu-O(2) bond
      strength, and other characteristic quantities. Cu(N)O(2) with odd-N tend to have
      larger adsorption energies than their even-N neighbors, with the exception of
      Cu(6)O(2), which has a relatively large adsorption energy resulting from the
      adsorption-induced 2D-to-3D structural transition in Cu(6). The energetically
      preferred spin-multiplicity of all the odd-N Cu(N)O(2) complexes is doublet; it
      is triplet for N = 2 and 4 and singlet for N = 6, 8, and 10.

PMID- 21732668
TI  - Computationally derived rules for persistence of C60 nanowires on recumbent
      pentacene bilayers.
AB  - The tendency for C(60) nanowires to persist on two monolayers of recumbent
      pentacene is studied using molecular dynamics (MD) simulations. A review of
      existing experimental literature for the tilt angle adopted by pentacene on noble
      metal surfaces shows that studies cover a limited range from 55 degrees  to 90
      degrees , motivating simulation studies of essentially the entire range of tilt
      angles (10 degrees -90 degrees ) to predict the optimum surface tilt angle for
      C(60) nanowire formation. The persistence of a 1D nanowire depends sensitively on
      this tilt angle, the amount of initial tensile strain, and the presence of
      surface step edges. At room temperature, C(60) nanowires oriented along the
      pentacene short axes persist for several nanoseconds and are more likely to occur
      if they reside between, or within, pentacene rows for phi <= ~60 degrees . The
      likelihood of this persistence increases the smaller the tilt angle. Nanowires
      oriented along the long axes of pentacene molecules are unlikely to form. The
      limit of stability of nanowires was tested by raising the temperature to 400 K.
      Nanowires located between pentacene rows survived this temperature rise, but
      those located initially within pentacene rows are only stable in the range phi(1)
      = 30 degrees -50 degrees . Flatter pentacene surfaces, that is, tilt angles above
      about 60 degrees , are subject to disorder caused by C(60) molecules "burrowing"
      into the pentacene surface. An initial strain of 5% applied to the C(60)
      nanowires significantly decreases the likelihood of nanowire persistence. In
      contrast, any appreciable surface roughness, even by half a monolayer in height
      of a third pentacene monolayer, strongly enhances the likelihood of nanowire
      formation due to the strong binding energy of C(60) molecules to step edges.

PMID- 21732669
TI  - LC-MS/MS quantification of sulforaphane and indole-3-carbinol metabolites in
      human plasma and urine after dietary intake of selenium-fortified broccoli.
AB  - This study aimed at developing a sensitive LC-MS/MS method for the quantification
      of sulforaphane (SFN) and indole-3-carbinol metabolites in plasma and urine after
      dietary intake of regular and selenium-fertilized broccoli using stable isotope
      dilution analysis. In a three-armed, placebo-controlled, randomized human
      intervention study with 76 healthy volunteers, 200 g of regular (485 MUg of total
      glucosinolates and <0.01 MUg of selenium per gram fresh weight) or selenium
      fertilized broccoli (589 MUg of total glucosinolates and 0.25 MUg of selenium per
      gram fresh weight) was administered daily for 4 weeks. Glucoraphanin and
      glucobrassicin metabolites quantified in plasma and urine were SFN-glutathione,
      SFN-cysteine, SFN-cysteinylglycine, SFN-acetylcysteine, and indole-3
      carboxaldehyde, indole-3-carboxylic acid, and ascorbigen, respectively. Dietary
      intake of selenium-fertilized broccoli increased serum selenium concentration
      analyzed by means of atomic absorption spectroscopy by up to 25% (p < 0.001), but
      affected neither glucosinolate concentrations in broccoli nor their metabolite
      concentrations in plasma and urine compared to regular broccoli.

PMID- 21732670
TI  - Molecular tumor clocks to study the evolution of drug resistance.
AB  - It is likely that drug resistance evolves after transformation. Exactly how these
      resistant cells arise is uncertain. This review outlines how the evolution of
      individual human cancers may be inferred by comparing genomic variation from
      different parts of the same tumor. The past of a tumor may help predict its
      responses to chemotherapy.

PMID- 21732671
TI  - Polysulfated xanthones: multipathway development of a new generation of dual
      anticoagulant/antiplatelet agents.
AB  - A multipathway strategy was used to evaluate the in vitro and in vivo
      antithrombotic effects of a new synthetic family of sulfated small molecules.
      Polysulfated xanthonosides showed highly effective anticoagulation effects in
      vitro, both in plasma (clotting times) and in whole human blood
      (thromboelastography), as well as in vivo (ip administration, mice).
      Physicochemical properties were assessed for mangiferin heptasulfate (7), which
      showed high solubility and stability in water and in human plasma and no putative
      hepatotoxicity in vivo. Mangiferin heptasulfate (7) was found to be a direct
      inhibitor of FXa, while persulfated 3,6-(O-beta-glucopyranosyl)xanthone (13)
      acted as a dual inhibitor of FXa (directly and by antithrombin III activation).
      By impedance aggregometry, compounds 7 and 13 exhibited the antiplatelet effect
      by inhibition of both arachidonic acid and ADP-induced platelet aggregation. Dual
      anticoagulant/antiplatelet agents, such as sulfated xanthonosides 7 and 13, are
      expected to lead to a new therapeutic approach for the treatment of both venous
      and arterial thrombosis.

PMID- 21732672
TI  - Hematopoietic stem cell gene therapy as a treatment for autoimmune diseases.
AB  - A key function of the immune system is to protect us from foreign pathogens such
      as viruses, bacteria, fungi and multicellular parasites. However, it is also
      important in many other aspects of human health such as cancer surveillance,
      tissue transplantation, allergy and autoimmune disease. Autoimmunity can be
      defined as a chronic immune response that targets self-antigens leading to tissue
      pathology and clinical disease. Autoimmune diseases, as a group of diseases that
      include type 1 diabetes, multiple sclerosis, rheumatoid arthritis and systemic
      lupus erythematosus, have no effective cures, and treatment is often based on
      long-term broad-spectrum immunosuppressive regimes. While a number of strategies
      aimed at providing disease specific treatments are being explored, one avenue of
      study involves the use of hematopoietic stem cells to promote tolerance. In this
      manuscript, we will review the literature in this area but in particular examine
      the relatively new experimental field of gene therapy and hematopoietic stem cell
      transplantation as a molecular therapeutic strategy to combat autoimmune disease.

PMID- 21732673
TI  - A single mutation in arrestin-2 prevents ERK1/2 activation by reducing c-Raf1
      binding.
AB  - Arrestins regulate the signaling and trafficking of G protein-coupled receptors
      (GPCRs). GPCR complexes with both nonvisual arrestins channel signaling to G
      protein-independent pathways, one of which is the activation of extracellular
      signal regulated kinase 1/2 (ERK1/2). Here we used alanine-scanning mutagenesis
      of residues on the nonreceptor-binding surface conserved between arrestin-2 and
      arrestin-3. We show that an Arg307Ala mutation significantly reduced arrestin-2
      binding to c-Raf1, whereas the binding of the mutant to active phosphorylated
      receptor and downstream kinases MEK1 and ERK2 was not affected. In contrast to
      wild-type arrestin-2, the Arg307Ala mutant failed to rescue arrestin-dependent
      ERK1/2 activation via beta2-adrenergic receptor in arrestin-2/3 double knockout
      mouse embryonic fibroblasts. Thus, Arg307 plays a specific role in arrestin-2
      binding to c-Raf1 and is indispensable in the productive scaffolding of c-Raf1
      MEK1-ERK1/2 signaling cascade. Arg307Ala mutation specifically eliminates
      arrestin-2 signaling through ERK, which makes arrestin-2-Arg307Ala the first
      signaling-biased arrestin mutant constructed. In the crystal structure the side
      chain of homologous arrestin-3 residue Lys308 points in a different direction.
      Alanine substitution of Lys308 does not significantly affect c-Raf1 binding to
      arrestin-3 and its ability to promote ERK1/2 activation, suggesting that the two
      nonvisual arrestins perform the same function via distinct molecular mechanisms.

PMID- 21732674
TI  - A multichannel model for the self-consistent analysis of coherent transport in
      graphene nanoribbons.
AB  - In this contribution, we analyze the multichannel coherent transport in graphene
      nanoribbons (GNRs) by a scattering matrix approach. We consider the transport
      properties of GNR devices of a very general form, involving multiple bands and
      multiple leads. The 2D quantum transport over the whole GNR surface, described by
      the Schrodinger equation, is strongly nonlinear as it implies calculation of self
      generated and externally applied electrostatic potentials, solutions of the 3D
      Poisson equation. The surface charge density is computed as a balance of carriers
      traveling through the channel at all of the allowed energies. Moreover, formation
      of bound charges corresponding to a discrete modal spectrum is observed and
      included in the model. We provide simulation examples by considering GNR
      configurations typical for transistor devices and GNR protrusions that find an
      interesting application as cold cathodes for X-ray generation. With reference to
      the latter case, a unified model is required in order to couple charge transport
      and charge emission. However, to a first approximation, these could be considered
      as independent problems, as in the example.

PMID- 21732675
TI  - Temporal changes in the levels of perfluorinated compounds in California women's
      serum over the past 50 years.
AB  - Serum samples collected from California women at different time periods: 1960s (n
      = 40), 1980s (n = 30), and 2009 (n = 35) were examined for the presence of 12
      perfluorinated compounds (PFCs) using an online SPE-HPLC-MS/MS method. At each
      time period, perfluorooctane sulfonate (PFOS) was present at the highest
      concentration, followed by perfluorooctanoic acid (PFOA, except in the 1960s). We
      found the highest levels of PFOS (median = 42.1 ng/mL) and perfluorohexane
      sulfonate (PFHxS, median = 1.56 ng/mL) in the 1960s samples, possibly reflecting
      widespread use of precursor PFCs. PFOS showed a statistically significant drop
      from the 1960s to the 1980s (28.8 ng/mL ) and to 2009 (9.0 ng/mL ), the latter
      being in agreement with national data. For PFOA, there was an approximately 10
      fold increase in median concentrations from the 1960s (0.27 ng/mL) to the 1980s
      (2.71 ng/mL), and a slight drop in the 2009 samples (2.08 ng/mL). For longer
      chain perfluorocarboxylic acids (PFCAs), there was a continuous build-up in serum
      from the 1960s to 2009. To our knowledge, this is the first study to investigate
      temporal changes of PFCs over the past 50 years.

PMID- 21732676
TI  - The native ensemble and folding of a protein molten-globule: functional
      consequence of downhill folding.
AB  - The continually emerging functional significance of intrinsic disorder and
      conformational flexibility in proteins has challenged the long-standing dogma of
      a well-defined structure contributing to a specific function. Molten-globular
      states, a class of proteins with significant secondary-structure but a fluid
      hydrophobic core, is one such example. They have however been difficult to
      characterize due to the complexity of experimental data and lack of computational
      avenues. Here, we dissect the folding mechanism of the alpha-helical molten
      globular protein NCBD from three fundamentally different approaches: statistical
      mechanical variable barrier model, C(alpha)-based Go-model and explicit water all
      atom molecular dynamics (MD) simulations. We find that NCBD displays the
      characteristics of a one-state globally downhill folder but is significantly
      destabilized. Using simulation techniques, we generate a highly constrained but a
      heterogeneous native ensemble of the molten-globule for the first time that is
      consistent with experimental data including small angle X-ray scattering (SAXS),
      circular dichroism (CD), and nuclear magnetic resonance (NMR). The resulting
      native ensemble populates conformations reported in other bound-forms providing
      direct evidence to the mechanism of conformational selection for binding multiple
      partners in this domain. Importantly, our simulations reveal a connection between
      downhill folding and large conformational flexibility in this domain that has
      been evolutionarily selected and functionally exploited resulting in large
      binding promiscuity. Finally, the multimodel approach we employ here serves as a
      powerful methodology to study mechanisms and suggests that the thermodynamic
      features of molten-globules fall within the array of folding mechanisms available
      to small single-domain proteins.

PMID- 21732677
TI  - Revisiting the Stober method: inhomogeneity in silica shells.
AB  - We demonstrate that the silica shell on nanoparticles formed by a typical Stober
      method is inhomogeneous in nature. The outer layer of the shell is chemically
      more robust than the inner layer, which can be selectively etched by hot water.
      Methods are developed to "harden" the soft silica shells. These new
      understandings are exploited to develop versatile and template-free approaches
      for fabricating sophisticated yolk-shell nanostructures.

PMID- 21732678
TI  - Chains of magnetosomes extracted from AMB-1 magnetotactic bacteria for
      application in alternative magnetic field cancer therapy.
AB  - Chains of magnetosomes extracted from AMB-1 magnetotactic bacteria are shown to
      be highly efficient for cancer therapy when they are exposed to an alternative
      magnetic field. When a suspension containing MDA-MB-231 breast cancer cells was
      incubated in the presence of various amounts of extracted chains of magnetosomes,
      the viability of these cells remained high in the absence of an alternative
      magnetic field. By contrast, when this suspension was exposed to an alternative
      magnetic field of frequency 183 kHz and field strengths of 20, 40, or 60 mT, up
      to 100% of these cells were destroyed. The antitumoral activity of the extracted
      chains of magnetosomes is demonstrated further by showing that they can be used
      to fully eradicate a tumor xenografted under the skin of a mouse. For that, a
      suspension containing ~1 mg of extracted chains of magnetosomes was administered
      within the tumor and the mouse was exposed to three heat cycles of 20 min, during
      which the tumor temperature was raised to ~43  degrees C. We also demonstrate the
      higher efficiency of the extracted chains of magnetosomes compared with various
      other materials, i.e., whole inactive magnetotactic bacteria, individual
      magnetosomes not organized in chains, and two different types of chemically
      synthesized superparamagnetic iron oxide nanoparticles currently tested for
      alternative magnetic field cancer therapy. The higher efficiency of the extracted
      chains of magnetosomes compared with that of the other nanoparticles is
      attributed to three factors: (i) a specific absorption rate higher for the
      magnetosomes than for the chemically synthesized superparamagnetic iron oxide
      nanoparticles, (ii) a more uniform heating for the chains of magnetosomes than
      for the individual magnetosomes and (iii) the ability of the chains of
      magnetosomes to penetrate within the cancer cells or bind at the cell membrane
      following the application of the alternative magnetic field, which enables
      efficient cell destruction. Biodistribution studies revealed that extracted
      chains of magnetosomes administered directly within xenografted breast tumors
      progressively left the tumors during the 14 days following their administration
      and were then eliminated in large proportion in the feces.

PMID- 21732679
TI  - Weak temperature dependence of structure in hydrophobic polyelectrolyte aqueous
      solution (PSSNa): correlation between scattering and viscosity.
AB  - We study in this paper, either in the semidilute regime by small angle scattering
      or in dilute and semidilute unentangled regimes by viscosimetric measurements,
      the influence of temperature on the structure of aqueous solutions of an
      hydrophobic polyelectrolyte, poly(styrene-co-sodium styrene sulfonate). There is
      a strong consistency between the two methods: the very weak dependence over
      temperature at high chemical charge is increased for lower charge fractions,
      i.e., when hydrophobicity is increased. The solvent quality is thus modified,
      whereas, for comparison, the hydrophilic polyelectrolyte poly(acrylamide-co
      sodium-2-acrylamido-2-methylpropane sulfonate), shows a structure totally
      independent of temperature, for all the charge fractions.

PMID- 21732680
TI  - Wettability conversion from superoleophobic to superhydrophilic on titania/single
      walled carbon nanotube composite coatings.
AB  - Superoleophobic surfaces were demonstrated on perfluorosilane-rendered titania
      (TiO(2))/single-walled carbon nanotube (SWNT) composite coatings. Scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM) observations
      revealed that SWNTs play a key role in the formation of overhanging structures
      and the nanoscale roughness on the coating surface, which compose the two
      critical morphologic factors for a superoleophobic surface. The wettability
      conversion from superoleophobic to superhydrophilic of the composite coatings was
      realized by the gradual decomposition of 1H,1H,2H,2H
      perfluorodecyltrichlorosilane (FDTS) on the coating surface using UV irradiation.
      Contact angle measurement on both smooth TiO(2) surface and rough composite
      coating surface under different UV irradiation time revealed that the wetting
      behavior of the liquids on the composite coating surface passes from the Cassie
      to the Wenzel and finally to the inversed-Cassie regime. Different liquids show
      different irradiation time for the wetting state change. By controlling the UV
      irradiation dose, liquids with surface tension difference smaller than 5 mN/m can
      exist in completely converse wetting states on the same coating surface, that is,
      superphobic for one liquid while superphilic for another with lower surface
      tension. Mixed organic liquids with different surface tension can be completely
      separated through a coated grid using this wettability tuning technique.

PMID- 21732682
TI  - Palladium-catalyzed C-S coupling: access to thioethers, benzo[b]thiophenes, and
      thieno[3,2-b]thiophenes.
AB  - The first C-S bond formation/cross-coupling/cyclization domino reaction using
      thiourea as a cheap and easy to handle dihydrosulfide surrogate has been
      developed. Structurally important biarylthioether, benzo[b]thiophenes, and
      thieno[3,2-b]thiophene scaffolds are provided in high yield.

PMID- 21732683
TI  - Regioselective carbon-carbon bond cleavage in the oxidation of
      cyclopropenylcarbinols.
AB  - The strained double bond of cyclopropenylcarbinols undergoes a facile oxidation
      reaction to lead to unsaturated carbonyl derivatives. The distribution of the
      formed products depends on the relative stability of carbon-centered radical
      species, and the Sharpless kinetic resolution leads to enantiomerically pure
      Baylis-Hillman enal adducts.

PMID- 21732684
TI  - pH-Dependent reactivity for glycyl-L-tyrosine in carboxypeptidase-A-catalyzed
      hydrolysis.
AB  - The dipeptide glycyl-L-tyrosine (GY) can be either a substrate for
      carboxypeptidase A (CPA) or an inhibitor, depending on pH. In this work, we
      investigate the pH-dependent reactivity of this dipeptide in CPA-catalyzed
      hydrolysis using a combined quantum mechanical and molecular mechanical method.
      It is shown that the monoionic form of the dipeptide, prevalent at high pH,
      chelates the active site zinc ion, rendering the enzyme inactive. This inhibitory
      form is consistent with an earlier X-ray structure of the CPA-GY complex. On the
      other hand, the prevailing di-ionic form of the dipeptide at low pH was found to
      undergo hydrolysis via a nucleophilic mechanism, leading to an acyl-enzyme
      complex. The stability of this reaction intermediate is consistent with previous
      low-temperature solid-state NMR results. The calculated overall free-energy
      barrier of 20.1 kcal/mol is in excellent agreement with the experimental value of
      19.9 kcal/mol.

PMID- 21732685
TI  - Atomic-scale characterization of graphene grown on copper (100) single crystals.
AB  - Growth of graphene on copper (100) single crystals by chemical vapor deposition
      has been accomplished. The atomic structure of the graphene overlayer was studied
      using scanning tunneling microscopy. A detailed analysis of moire superstructures
      present in the graphene topography reveals that growth occurs in a variety of
      orientations over the square atomic lattice of the copper surface. Transmission
      electron microscopy was used to elucidate the crystallinity of the grown
      graphene. Pristine, defect-free graphene was observed over copper steps, corners,
      and screw dislocations. Distinct protrusions, known as "flower" structures, were
      observed on flat terraces, which are attributed to carbon structures that depart
      from the characteristic honeycomb lattice. Continuous graphene growth also occurs
      over copper adatoms and atomic vacancies present at the single-crystal surface.
      The copper atom mobility within vacancy islands covered with suspended graphene
      sheets reveals a weak graphene-substrate interaction. The observed continuity and
      room-temperature vacancy motion indicates that copper mobility likely plays a
      significant role in the mechanism of sheet extension on copper substrates.
      Lastly, these results suggest that the quality of graphene grown on copper
      substrates is ultimately limited by nucleation at the surface of the metal
      catalyst.

PMID- 21732686
TI  - Sombrero-shaped plasmonic nanoparticles with molecular-level sensitivity and
      multifunctionality.
AB  - We demonstrate top-down synthesis of monodisperse plasmonic nanoparticles
      designed to contain internal Raman hot spots. Our Raman-active nanoparticles are
      fabricated using nanoimprint lithography and thin-film deposition and are
      composed of novel internal structures with sublithographic dimensions: a disk
      shaped Ag core, a Petri-dish-shaped SiO(2) base whose inner surface is coated
      with Ag film, and a sub-10 nm scale circular gap between the core and the base.
      Confocal Raman measurements and electromagnetic simulations show that Raman hot
      spots appear at the inside perimeter of individual nanoparticles and serve as the
      source of a 1000-fold improvement of minimum molecular detection level that
      enables detection of signals from a few molecules near hot spots. A multimodality
      version of these nanoparticles, which includes the functionality offered by
      magnetic multilayers, is also demonstrated. These results illustrate the
      potential of direct fabrication for creating exotic monodisperse nanoparticles,
      which combine engineered internal nanostructures and multilayer composite
      materials, for use in nanoparticle-based molecular imaging and detection.

PMID- 21732687
TI  - Enantiospecific synthesis of genetically encodable fluorescent unnatural amino
      acid L-3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid.
AB  - Fluorescent unnatural amino acids (UAAs), when genetically incorporated into
      proteins, can provide unique advantages for imaging biological processes in vivo.
      Synthesis of optically pure L-enantiomer of fluorescent UAAs is crucial for their
      effective application in live cells. An efficient six-step synthesis of L-3-(6
      acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (L-Anap), a genetically
      encodable and polarity-sensitive fluorescent UAA, has been developed. The
      synthesis takes advantage of a high-yield and enantiospecific Fukuyama-Mitsunobu
      reaction as the key transformation.

PMID- 21732688
TI  - Magnetic sponge prepared with an alkanedithiol-bridged network of nanomagnets.
AB  - The magnetic dipole-dipole interaction between nanomagnets having huge magnetic
      moments can have a strength comparable to that of the van der Waals interaction
      between them, and it can be manipulated by applying an external magnetic field of
      conventional strength. Therefore, the cooperation between the dipole-dipole
      interaction and the applied magnetic field allows the magnetic moments of
      nanomagnets to be aligned and organized in an ordered manner. In this work, a
      network of magnetic nanoparticles connected with flexible long-alkyl-chain
      linkers was designed to develop a "magnetic sponge" capable of absorbing and
      desorbing guest molecules with changes in the applied magnetic field. The
      magnetization of the sponge with long-alkyl-chain bridges (30 C atoms) exhibited
      a 500% increase after cooling in the presence of an applied field of 7 T relative
      to that in the absence of a magnetic field. Cooling in a magnetic field leads to
      anisotropic stretching in the sponge due to reorganization of the nanomagnets
      along the applied field, in contrast to the isotropic organization under zero
      field conditions. Such magnetic-responsive organization and reorganization of the
      magnetic particle network significantly influences the gas absorption capacity of
      the nanopores inside the material. The absorption and desorption of guests in an
      applied magnetic field at low temperature can be regarded as a fascinating
      "breathing feature" of our magnetic sponge.

PMID- 21732689
TI  - Structure-guided design of cell wall biosynthesis inhibitors that overcome beta
      lactam resistance in Staphylococcus aureus (MRSA).
AB  - beta-Lactam antibiotics have long been a treatment of choice for bacterial
      infections since they bind irreversibly to Penicillin-Binding Proteins (PBPs),
      enzymes that are vital for cell wall biosynthesis. Many pathogens express drug
      insensitive PBPs rendering beta-lactams ineffective, revealing a need for new
      types of PBP inhibitors active against resistant strains. We have identified
      alkyl boronic acids that are active against pathogens including methicillin
      resistant S. aureus (MRSA). The crystal structures of PBP1b complexed to 11
      different alkyl boronates demonstrate that in vivo efficacy correlates with the
      mode of inhibitor side chain binding. Staphylococcal membrane analyses reveal
      that the most potent alkyl boronate targets PBP1, an autolysis system regulator,
      and PBP2a, a low beta-lactam affinity enzyme. This work demonstrates the
      potential of boronate-based PBP inhibitors for circumventing beta-lactam
      resistance and opens avenues for the development of novel antibiotics that target
      Gram-positive pathogens.

PMID- 21732690
TI  - Porous coordination polymer hybrid device with quartz oscillator: effect of
      crystal size on sorption kinetics.
AB  - A new strategy to synthesize monodispersed porous coordination polymer (PCP)
      nanocrystals at room temperature was developed and utilized for the formation of
      PCP thin films on gold substrates with fine control over the crystal sizes using
      the coordination modulation method. Hybridization of these PCP thin films with an
      environment-controlled quartz crystal microbalance system allowed determining the
      adsorption properties for organic vapors (methanol and hexane). In the case of
      high sensitivity (at the low-concentration dosing of analytes), the sensor
      response depended on the crystal size but not on the type of analyte. In
      contrast, at the high-concentration dosing, a clear dependence of the sorption
      kinetics on the analyte was observed due to significant sorbate-sorbate
      interaction.

PMID- 21732691
TI  - Investigation on the interaction between ilaprazole and bovine serum albumin
      without or with different C-ring flavonoids from the viewpoint of food-drug
      interference.
AB  - The interaction between ilaprazole and bovine serum albumin (BSA) has been
      investigated in the absence and presence of four popular flavonoids with
      different C-ring structures, quercetin, luteolin, taxifolin, and (+)-catechin, by
      means of fluorescence spectroscopy. The results indicated that ilaprazole had a
      strong ability to quench the intrinsic fluorescence of BSA, and site marker
      competitive experiments indicated that the binding of ilaprazole to BSA primarily
      took place in subdomain IIA. The quenching process of ilaprazole with BSA was
      easily affected by flavonoids,; however, they did not change the quchenching
      mechanism of ilaprazole with BSA, whereas all of the fluorescence quenching was
      initiated by a static quenching procedure combining with nonradiative energy
      transfer. The presence of flavonoids decreased the quenching constants of
      ilaprazole with BSA from 2.2 to 23.7% and decreased the binding constants from
      73.7 to 98.3%, which depended on the different flavonoids' structures. The
      decreased binding constants and unchangeable spatial distance of ilaprazole with
      BSA by the introduction of quercetin, luteolin, and taxifolin may result from the
      competition of flavonoids and ilaprazole binding to BSA, whereas in the presence
      of (+)-catichin, decreased binding constants and increased spatial distance
      possibly resulted from the formation of a ternary ilaprazole-BSA-(+)-catechin
      complex. All of these results may have relevant consequences in rationalizing the
      interferences of common food to gastric ulcer treatments.

PMID- 21732692
TI  - Highly porous core-shell polymeric fiber network.
AB  - Core-shell nanofibers are of great interest in the field of tissue engineering
      and cell biology. We fabricated porous core-shell fiber networks using an
      electrospinning system with a water-immersed collector. We hypothesized that the
      phase separation and solvent evaporation process would enable the control of the
      pore formation on the core-shell fiber networks. To synthesize porous core-shell
      fiber networks, we used polycaprolactone (PCL) and gelatin. Quantitative analysis
      showed that the sizes of gelatin-PCL core-shell nanofibers increased with PCL
      concentrations. We also observed that the shapes of the pores created on the PCL
      fiber networks were elongated, whereas the gelatin-PCL core-shell fiber networks
      had circular pores. The surface areas of porous nanofibers were larger than those
      of the nonporous nanofibers due to the highly volatile solvent and phase
      separation process. The porous core-shell fiber network was also used as a matrix
      to culture various cell types, such as embryonic stem cells, breast cancer cells,
      and fibroblast cells. Therefore, this porous core-shell polymeric fiber network
      could be a potentially powerful tool for tissue engineering and biological
      applications.

PMID- 21732693
TI  - Gas chromatography-mass spectrometry assessment of amines in Port wine and grape
      juice after fast chloroformate extraction/derivatization.
AB  - A simple, reliable, and sensitive gas chromatography-mass spectrometry method for
      the quantification of volatile and nonvolatile biogenic amines in Port wines and
      grape juices was developed and evaluated. The method was based on a previously
      reported two-phase derivatization procedure with isobutyl chloroformate in a
      toluene medium, which provides a quantitative reaction in 10 min. Following the
      derivatization step, the excess of reagent was eliminated by treatment with
      alkaline methanol. The derivatization procedure was performed directly on 1 mL of
      sample, avoiding any fastidious and time-consuming cleanup extraction steps. The
      method allows the simultaneous quantification of 22 amines, which can be found in
      wines: methylamine, dimethylamine, ethylamine, diethylamine, propylamine,
      isopropylamine, butylamine, isobutylamine, amylamine, isoamylamine, 2
      methylbutylamine, hexylamine, pyrrolidine, piperidine, morpholine, 1,3
      diaminopropane, putrescine, cadaverine, 1,6-diaminohexane, 2-phenylethylamine,
      histamine, and tyramine. Because of the fact that histamine and tyramine
      derivatives are degraded during the isobutyl chloroformate elimination step, the
      corresponding determination was made after removal of the excess of derivatizing
      reagent by evaporating an aliquot of the toluene layer obtained after the
      reaction. The presented method showed excellent analytical characteristics in
      what linearity, recovery, repeatability, and limit of detections were respected.
      It was used to assess the concentration of biogenic amines in juice grapes and
      Tawny and Vintage Port wines with different aging times. On the whole, the total
      content of amines in Port wines was low. Most of the amines found in wines have
      their origin in the raw material used for their elaboration, so the Port
      winemaking process is not prone to the production of this kind of compounds.
      Total biogenic amine contents have shown a decrease with the aging of both types
      of Port wines.

PMID- 21732694
TI  - Determination of 67Zn distribution in navy bean (Phaseolus vulgaris L.) after
      foliar application of 67Zn-lignosulfonates using isotope pattern deconvolution.
AB  - The improvement of Zn fertilizers requires new techniques to evaluate their
      efficacy. In this paper, the (67)Zn stable isotope was used as tracer of several
      Zn-lignosulfonate complexes to study the foliar-applied Zn uptake and
      distribution behavior in the plant, compared with ZnEDTA. Navy bean plants (
      Phaseolus vulgaris L.) were grown hydroponically in a Zn-free nutrient solution,
      and six modified lignosulfonates and EDTA complexed with (67)Zn were used in
      foliar application in the young leaves as Zn sources. Zinc isotopes in roots,
      stems, and sprayed and unsprayed leaves were determined by ICP-MS, and signal
      interferences caused by the compounds of the digested vegetal samples were
      corrected. The mathematical procedure of isotope pattern deconvolution allowed
      the minimization of the uncertainty in the measured molar fractions of Zn from
      fertilizer or from natural sources. Significant differences in Zn use and
      distribution were observed among the fertilizers when the calculated
      concentrations of Zn from the fertilizer were compared, whereas they were
      unnoticeable attending to the total Zn in plant tissues, usually determined at
      the conventional studies. By foliar spray, higher Zn uptake and mobilization to
      leaves and stems were achieved with (67)ZnEDTA than with (67)Zn-LS complexes. The
      ultrafiltered LS and phenolated LS showed slightly better ability to provide Zn
      to the bean plants than the other LS. The foliar-applied Zn use and distribution
      in the plant were related with the stability of the Zn-lignosulfonates complexes.
      Those presenting the lower stability versus pH, but the highest complexing
      capacity, were slightly more suitable to supply foliar-applied Zn to navy beans.

PMID- 21732695
TI  - Synthesis of silver/poly(2-hydroxyethyl methacrylate) particles via a combination
      of inverse miniemulsion and silver ion reduction in a "nanoreactor".
AB  - Silver salt/poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hybrid particles were
      first prepared by inverse miniemulsion polymerization of 2-hydroxyethyl
      methacrylate (HEMA) with silver tetrafluoroborate (AgBF(4)) as a lipophobe. High
      silver salt loads of up to 13% with respect to the disperse phase were achieved.
      The silver/poly(HEMA) hybrid particles were subsequently formed via a gas-phase
      in situ reduction of AgBF(4) by hydrazine on the surfaces of silver
      salt/poly(HEMA) particles. The formation of silver nanoparticles was confirmed by
      UV-vis spectroscopy and X-ray diffraction. The morphology of the hybrid particles
      of silver salt/poly(HEMA) and silver/poly(HEMA) was fully characterized by
      transmission electron microscopy (TEM), atomic force microscopy (AFM), and
      dynamic light scattering (DLS). The influence of the reaction parameters
      including the type and amount of cosolvent, salt content, and type of surfactant
      on the particle properties and colloidal stability during the reduction process
      was thoroughly investigated.

PMID- 21732696
TI  - Phenolic metabolism in grafted versus nongrafted cherry tomatoes under the
      influence of water stress.
AB  - Use of grafts using rootstocks capable of palliating the effects of water stress
      can be a possible solution to reduce yield losses. For response to stress, plants
      can induce the metabolism of phenylpropanoids. The aim of the present work is to
      determine the response of reciprocal grafts made between one tolerant cherry
      tomato cultivar, Zarina, and a more sensitive cultivar, Josefina. The analysis of
      the phenylpropanoids pathway was carried out both enzymatically and
      metabolically. DAHP synthase, shikimate dehydrogenase, phenylalanine ammonium
      lyase, cinnamate 4-hydroxylase, and 4-coumarate CoA ligase activities were
      determined, and characteristic metabolites from the pathway were measured by
      means of HPLC-MS. Growth in the grafts JosxZar and ZarxJos was not appreciably
      affected by stress. JosxZar had increased concentrations of phenolic compounds
      after water stress. This could be correlated with the greater activity of
      synthesis enzymes as well as a decrease in phenol-degrading enzymes. Phenolic
      metabolism is more influenced by the aerial part, and therefore it is concluded
      that the capacity of inducing tolerance in rootstocks depends on the genotype of
      the shoot.

PMID- 21732697
TI  - Effects of tyrosinase and laccase on oat proteins and quality parameters of
      gluten-free oat breads.
AB  - Effects of a Trichoderma reesei tyrosinase (TYR) and a Trametes hirsuta laccase
      (LAC) on breadmaking performance of gluten-free oat flour were investigated by
      SDS-PAGE analysis of oat protein fractions, large deformation rheology, and
      microscopy of the doughs, as well as on the basis of specific volume and firmness
      of the gluten-free breads. TYR induced the formation of higher molecular weight
      proteins in the SDS-PAGE assay. Microscopical analysis showed more intensive
      protein aggregation in the TYR-treated dough than in the dough without TYR. TYR
      also increased the firmness of the dough, which was assumed to be because of the
      cross-linking of oat globulins. LAC did not affect the oat globulins. TYR alone,
      or together with a commercial Thermomyces lanuginosus xylanase (XYL), increased
      significantly the specific volume of the gluten-free oat bread. A combination of
      TYR and XYL also increased the softness of the bread, whereas a combination of
      LAC and XYL improved the specific volume but did not affect the softness of oat
      bread. The results thus indicate that cross-linking of oat globulins by TYR,
      especially with the addition of XYL, was beneficial for improving the texture of
      gluten-free oat bread.

PMID- 21732698
TI  - Purification of the human SMN-GEMIN2 complex and assessment of its stimulation of
      RAD51-mediated DNA recombination reactions.
AB  - A deficiency in the SMN gene product causes the motor neuron degenerative disease
      spinal muscular atrophy. GEMIN2 was identified as an SMN-interacting protein, and
      the SMN-GEMIN2 complex constitutes part of the large SMN complex, which promotes
      the assembly of the spliceosomal small nuclear ribonucleoprotein (snRNP). In
      addition to its splicing function, we previously found that GEMIN2 alone
      stimulates RAD51-mediated recombination in vitro, and functions in DNA double
      strand-break (DSB) repair through homologous recombination in vivo. However, the
      function of SMN in homologous recombination has not been reported. In the present
      study, we successfully purified the SMN-GEMIN2 complex as a fusion protein. The
      SMN-GEMIN2 fusion protein complemented the growth-defective phenotype of GEMIN2
      knockout cells. The purified SMN-GEMIN2 fusion protein enhanced the RAD51
      mediated homologous pairing much more efficiently than GEMIN2 alone. SMN-GEMIN2
      possessed DNA-binding activity, which was not observed with the GEMIN2 protein,
      and significantly stimulated the secondary duplex DNA capture by the RAD51-single
      stranded DNA complex during homologous pairing. These results provide the first
      evidence that the SMN-GEMIN2 complex plays a role in homologous recombination, in
      addition to spliceosomal snRNP assembly.

PMID- 21732699
TI  - Spectral modification and catalytic inhibition of human cytochromes P450 1A1,
      1A2, 1B1, 2A6, and 2A13 by four chemopreventive organoselenium compounds.
AB  - Several organoselenium compounds including benzyl selenocyanate (BSC), 1,2
      phenylenebis(methylene)selenocyanate (o-XSC), 1,3
      phenylenebis(methylene)selenocyanate (m-XSC), and 1,4
      phenylenebis(methylene)selenocyanate (p-XSC) have been shown to prevent cancers
      caused by polycyclic aromatic hydrocarbons (PAHs) and 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) in experimental animals; these chemical carcinogens are
      activated by human P450 1 and 2A family enzymes, respectively, to carcinogenic
      metabolites. In this study, we examined whether these selenium compounds interact
      with and inhibit human P450 1 and 2A enzymes in vitro. Four organoselenium
      compounds induced reverse Type I binding spectra with P450 1A1, 1A2, and 1B1 and
      Type I binding spectra with P450 2A6 and 2A13. The spectral dissociation
      constants (K(s)) for the interaction of P450 1B1 with these chemicals were 3.6
      5.7 MUM; the values were lower than those with seen with P450 1A1 (19-30 MUM) or
      1A2 (6.3-13 MUM). The K(s) values for Type I binding of P450 2A13 with m-XSC and
      BSC were both 0.20 MUM; the values were very low compared to those for the
      interaction of P450 2A6 with m-XSC (5.7 MUM) and BSC (2.0 MUM). Four selenium
      compounds directly inhibited 7-ethoxyresorufin O-deethylation activities
      catalyzed by P450 1A1, 1A2, and 1B1 with IC(50) values <1.0 MUM, except for the
      inhibition of P450 1A2 by BSC (1.3 MUM). Coumarin 7-hydroxylation activities of
      P450 2A13 were more inhibited by four selenium compounds than those of P450 2A6,
      with IC(50) values of 0.22-1.4 MUM for P450 2A13 and 2.4-6.2 MUM for P450 2A6.
      Molecular docking studies of the interaction of four organoselenium compounds
      with human P450 enzymes suggest that these chemicals can be docked into the
      active sites of these human P450 enzymes and that the sites of the selenocyanate
      functional groups of these chemicals differ between the P450 1 and 2A family
      enzymes.

PMID- 21732700
TI  - Pure white organic light-emitting diode with lifetime approaching the longevity
      of yellow emitter.
AB  - A high-efficiency pure white organic light-emitting diode was fabricated with
      lifetime approaching that of the low-excitation-energy (yellow) emitter
      containing counterpart, or six times that of the deep-blue counterpart. The white
      device was composed of two emission layers with mixed hosts of different
      compositions. They were respectively doped with yellow rubrene and deep-blue 4,4'
      bis-[4-{N,N,N',N'- tetrakis-(4-fluoro-diphenylamino)-phenyl}-vinyl]-biphenyl. The
      resulting efficiency was 6.0 lm/W (12.4 cd/A) at 20 mA/cm(2). The long device
      lifetime may be attributed to the double mixed-host architecture employed that
      effectively dispersed the injected carriers into three different recombination
      zones and consequently diluted the damaging effect arising from the accumulated
      charge from un-recombined carriers, hence leading to a markedly improved
      lifespan.

PMID- 21732701
TI  - Metabolic profiling of lung granuloma in Mycobacterium tuberculosis infected
      guinea pigs: ex vivo 1H magic angle spinning NMR studies.
AB  - A crucial and distinctive feature of tuberculosis infection is that Mycobacterium
      tuberculosis (Mtb) resides in granulomatous lesion at various stages of disease
      development and necrosis, an aspect that is little understood. We used a novel
      approach, applying high resolution magic angle spinning nuclear magnetic
      resonance spectroscopy (HRMAS NMR) directly to infected tissues, allowing us to
      study the development of tuberculosis granulomas in guinea pigs in an untargeted
      manner. Significant up-regulation of lactate, alanine, acetate, glutamate,
      oxidized and the reduced form of glutathione, aspartate, creatine,
      phosphocholine, glycerophosphocholine, betaine, trimethylamine N-oxide, myo
      inositol, scyllo-inositol, and dihydroxyacetone was clearly visualized and was
      identified as the infection progressed. Concomitantly, phosphatidylcholine was
      down-regulated. Principal component analysis of NMR data revealed clear group
      separation between infected and uninfected tissues. These metabolites are
      suggestive of utilization of alternate energy sources by the infiltrating cells
      that generate much of the metabolites in the increasingly necrotic and hypoxic
      developing granuloma through the glycolytic, pentose phosphate, and tricarboxylic
      acid pathways. The most relevant changes seen are, surprisingly, very similar to
      metabolic changes seen in cancer during tumor development.

PMID- 21732702
TI  - Side-chain peptide-synthetic polymer conjugates via tandem "ester-amide/thiol
      ene" post-polymerization modification of poly(pentafluorophenyl methacrylate)
      obtained using ATRP.
AB  - Herein the concept of tandem postpolymerization modification as a versatile route
      to synthesize well-defined, highly functionalized polymers is introduced.
      Poly(pentafluorophenyl methacrylate) obtained by atom transfer radical
      polymerization was first modified with allylamine, which displaces the active
      ester to give well-defined polymers with pendant alkene groups, which are
      difficult to obtain by direct (radical) polymerization of allylic-functional
      monomers. The produced poly(allylmethacrylamide) was modified by a second
      postpolymerization modification reaction with a thiol-terminated peptide (CVPGVG)
      using AIBN as the radical source. NMR, IR, and SEC demonstrated successful
      conjugation onto the polymer to give a polymer-peptide hybrid material. This
      versatile strategy should extend the scope of controlled radical polymerization
      and "click"-type reactions.

PMID- 21732703
TI  - The case for less, not more, US FDA regulation.

PMID- 21732704
TI  - US FDA Modernization Act, section 114: uses, opportunities and implications for
      comparative effectiveness research.
AB  - BACKGROUND: Section 114 of the 1997 US FDA Modernization Act (FDAMA) is an
      important vehicle for pharmaceutical companies to promote the economic value of
      their drugs to formulary decision makers, but little is known about how the
      Section has been interpreted and used. METHODS: We conducted a web-based survey
      of a convenience sample of 35 outcomes directors of major pharmaceutical and
      biotechnology companies. We asked them about their interpretation of, and
      experiences with, Section 114, as well as their views regarding the FDA's role in
      the matter, and whether the advent of comparative effectiveness research (CER)
      will affect the use of Section 114 promotions. RESULTS: Of the 35 experts, 16
      (46%) completed the survey. 81% stated they always or frequently consider using
      Section 114 when making promotional claims for drugs. 75% stated that the FDA
      should issue guidance on how to make such promotions to payers, especially what
      qualifies as "healthcare economic information" and "competent and reliable
      scientific evidence." Most expected to use Section 114 to a greater extent in the
      future, and agreed that the increased focus on CER would increase Section 114
      use. CONCLUSIONS: The survey suggests strong awareness about Section 114 among
      the outcomes directors and some use of the Section for promotional purposes. It
      also reflects a belief that CER will increase use of Section 114 promotions, and
      that guidance from the FDA is needed. More clarity - and, ideally, flexible
      interpretation - from the FDA is warranted, especially given the rise of CER.

PMID- 21732705
TI  - Prolonging assembly through dissociation: a self-assembly paradigm in
      microtubules.
AB  - We study a one-dimensional model of microtubule assembly and disassembly in which
      GTP bound to tubulins within the microtubule undergoes stochastic hydrolysis. In
      contrast to models that consider only a cap of GTP-bound tubulin, stochastic
      hydrolysis allows GTP-bound tubulin remnants to exist within the microtubule. We
      find that these buried GTP remnants enable an alternative mechanism of recovery
      from shrinkage and enhances fluctuations of filament lengths. Under conditions
      for which this alternative mechanism dominates, an increasing depolymerization
      rate leads to a decrease in dissociation rate and thus a net increase in
      assembly.

PMID- 21732706
TI  - Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma
      proteins.
AB  - The binding of nateglinide (NA) enantiomers with human plasma (HP), human serum
      albumin (HSA) and bovine serum albumin (BSA) was investigated. The protein
      binding was studied over a drug concentration range of 5-100 MUM at a protein
      concentration of 600 MUM. Unbound drug concentrations were determined by direct
      chiral liquid chromatography using chiralcel OJ-RH column. At therapeutic drug
      concentrations, the protein binding of each enantiomer was >98%. The results
      showed that the binding of NA enantiomers was stereoselective, mutually
      competitive and non-linear. The binding characteristics were, however, opposite
      for the two most important plasma binding proteins. Opposite stereo-selectivity
      was observed between BSA and HSA while stereo-selectivity was identical between
      HSA and HP. Scatchard analysis was used to illustrate the different binding
      affinities of NA enantiomers to BSA, HSA and HP. The interaction between
      enantiomers observed in HP and serum albumins was confirmed as a competitive type
      interaction at the high affinity site. Scatchard analysis was used to illustrate
      the different binding affinities of NA enantiomers to BSA, HSA and HP.

PMID- 21732707
TI  - The social constructions of unwanted pregnancy and abortion in Lima, Peru.
AB  - Although modern contraceptive use in Peru has increased, many women still face
      unwanted or unplanned pregnancies and abortions remain high despite the
      illegality of elective pregnancy termination. To improve understanding of how men
      and women make reproductive decisions, we conducted this study in Lima. Fifty-two
      18-37 year old low- and middle-income women and men participated in in-depth
      interviews and focus groups. Reproductive planning constitutes a worry among
      participants. The paradigm of contraception, pregnancy, childbearing and
      pregnancy termination is complex and contained within a context of contradictory
      pressures toward women: while women feel the need to be autonomous in all realms
      of their lives, they also need to meet the traditional roles associated with
      sexuality and childbearing and rearing. The woman, her partner and family members
      take part in reproductive decisions. However, participants expressed difficulties
      preventing unwanted pregnancies and social stigma if they resorted to abortion
      or, interestingly, if they continued a pregnancy when involved in a socially
      undesirable personal situation. Abortion-related stigma generated fear and guilt
      in addition to safety concerns given the unsafe, clandestine contexts in which
      pregnancy termination takes place. Despite these concerns, interviewees often
      opted for abortion for personal reasons, which were primarily economic.

PMID- 21732708
TI  - The impact of reducing financial barriers on utilisation of a primary health care
      facility in Rwanda.
AB  - This study investigates the impact of subsidising community-based health
      insurance (mutuelle) enrolment, removing point-of-service co-payments, and
      improving service delivery on health facility utilisation rates in Mayange, a
      sector of rural Rwanda of approximately 25,000 people divided among five
      'imidugudu' or small villages. While comprehensive service upgrades were
      introduced in the Mayange Health Centre between April 2006 and February 2007,
      utilisation rates remained similar to comparison sites. Between February 2007 and
      April 2007, subsidies for mutuelle enrolment established virtually 100% coverage.
      Immediately after co-payments were eliminated in February 2007, patient visits
      levelled at a rate triple the previous value. Regression analyses using data from
      Mayange and two comparison sites indicate that removing financial barriers
      resulted in about 0.6 additional annual visits for curative care per capita.
      Although based on a single local pilot, these findings suggest that in order to
      achieve improved health outcomes, key short-term objectives include improved
      service delivery and reduced financial barriers. Based on this pilot, higher
      utilisation rates may be affected if broader swaths of the population are
      enrolled in mutuelle and co-payments are eliminated. Health leaders in Rwanda
      should consider further studies to determine if the impact of eliminating co
      payments and increasing subsidies for mutuelle enrolment as seen in Mayange holds
      at greater levels of scale. Broader studies to better elucidate the impact of
      enrolment subsidies and co-payment subsidies on utilisation, health outcomes, and
      costs would also provide policy insights.

PMID- 21732709
TI  - A Congolese-US participatory action research partnership to rebuild the lives of
      rape survivors and their families in eastern Democratic Republic of Congo.
AB  - The Democratic Republic of Congo (DRC) remains an all-too-potent reminder of how
      war, human rights violations and their related health and economic impacts can
      devastate a society. The last decade has seen the use of rape as a weapon of war
      in the DRC, where rebels and soldiers subject women and girls to brutalising
      attacks, rape, torture and mutilation. Survivors of sexual and gender-based
      violence (SGBV) are often further traumatised by infections, disease, poverty,
      stigma and social isolation. Substantial evidence exists showing an association
      between social determinants (e.g., poverty, stress and trauma, stigma, lack of
      access to health care) and health; however, limited research has been conducted
      to elucidate these relationships or to develop and test interventions to change
      social determinants of health, especially in conflict and post-conflict settings
      such as the DRC. The purpose of this article is to present a Congolese-US
      community-academic research partnership to obtain evidence to develop and
      implement a sustainable intervention to begin to address the social determinants
      of health, including poverty and traumatic stress for survivors of SGBV and their
      families in the South Kivu province of eastern DRC.

PMID- 21732710
TI  - Methodological characteristics of the national dietary surveys carried out in the
      European Union as included in the European Food Safety Authority (EFSA)
      Comprehensive European Food Consumption Database.
AB  - In 2009 competent organisations in the European Union provided the European Food
      Safety Authority (EFSA) with data from the most recent national dietary survey at
      the level of individuals' consumption. Twenty different Member States provided
      EFSA with data from 22 different national dietary surveys, with consumption
      figures for adults and, when available, for children. Member States' dietary data
      were assembled into the EFSA Comprehensive European Food Consumption Database. In
      this paper an overview of the methodologies and protocols employed in the
      different national dietary surveys is provided. Specifically, details about
      dietary assessment methods, interview administration, sampling design, portion
      size estimation, dietary software, evaluation of under-reporting and non-dietary
      information collected are described. This information is crucial to evaluate the
      level of accuracy of food consumption data and to anticipate and acknowledge the
      utmost important sources of heterogeneity of national databases included in the
      Comprehensive Database. The Comprehensive Database constitutes a unique resource
      for the estimation of consumption figures across the European Union and
      represents a useful tool to assess dietary exposure to hazardous substances and
      nutrient intake in Europe. Nevertheless, the many substantial methodological
      differences that characterise the Comprehensive Database are acknowledged and
      critically discussed.

PMID- 21732711
TI  - Comparison of deposition in the USP and physical mouth-throat models with solid
      and liquid particles.
AB  - BACKGROUND: Experimental deposition was studied using three different mouth
      throat models: (1) the standard United States Pharmacopeia induction port (IP),
      (2) the idealized human mouth and throat replica developed by the University of
      Alberta (UofA replica), and (3) the conductive rubber mouth-throat cast from a
      human subject developed by Lovelace Respiratory Research Institute (LRRI cast).
      METHODS: Both solid and liquid monodispersed fluorescent particles in the size
      range of 2-30 MUm in diameter were delivered into the devices at flow rates of
      15, 30, and 60 L min(-1). For solid particles, the study was conducted with and
      without grease coating inside the devices to investigate the effects of particle
      bounce. CONCLUSIONS: Large amounts of rebounded particles were found for the IP
      and UofA replica without the coating treatment, while particle bounce was only
      observed at the large particle size for the LRRI cast. The UofA replica and LRRI
      cast agreed well for solid particles with coating treatments and liquid
      particles. The deposition results from this study were also compared to data of
      in vivo deposition studies from the literature. The deposition efficiencies in
      the UofA replica and LRRI cast were within the range of in vivo data, which
      showed a large scatter.

PMID- 21732712
TI  - Meeting an adult ally on the way out into the world: adolescent patients'
      experiences of useful psychotherapeutic ways of working at an age when
      independence really matters.
AB  - The aim of this study was to explore how adolescents in ongoing psychotherapies
      prefer their therapists to interact with them when they are establishing a
      therapeutic bond. Semi-structured qualitative interviews were held with 14
      patients. A hermeneutic-phenomenological approach was used to analyze interview
      transcripts. The participants' descriptions of important experiential dimensions
      in their interaction with their therapists clustered around five themes: the
      adolescents (1) feeling vulnerable and ambivalent in relationship with a
      potential helper when therapy started; the therapists (2) showed them that they
      were comfortable with being a therapist (3), strengthened their autonomy by
      establishing therapeutic boundaries, (4) showed that they recognized patients'
      individuality by respecting their personal boundaries, (5) helped them make their
      experiences understandable and meaningful, and (6) allowed mutuality and
      emotional closeness.

PMID- 21732713
TI  - The effects of metabolite molecules produced by drinking water-isolated bacteria
      on their single and multispecies biofilms.
AB  - The elucidation of the mechanisms by which diverse species survive and interact
      in drinking water (DW) biofilm communities may allow the identification of new
      biofilm control strategies. The purpose of the present study was to investigate
      the effects of metabolite molecules produced by bacteria isolated from DW on
      biofilm formation. Six opportunistic bacteria, viz. Acinetobacter calcoaceticus,
      Burkholderia cepacia, Methylobacterium sp., Mycobacterium mucogenicum,
      Sphingomonas capsulata and Staphylococcus sp. isolated from a drinking water
      distribution systems (DWDS) were used to form single and multispecies biofilms in
      the presence and absence of crude cell-free supernatants produced by the partner
      bacteria. Biofilms were characterized in terms of mass and metabolic activity.
      Additionally, several physiological aspects regulating interspecies interactions
      (sessile growth rates, antimicrobial activity of cell-free supernatants, and
      production of iron chelators) were studied to identify bacterial species with
      biocontrol potential in DWDS. Biofilms of Methylobacterium sp. had the highest
      growth rate and M. mucogenicum biofilms the lowest. Only B. cepacia was able to
      produce extracellular iron-chelating molecules. A. calcoaceticus, B. cepacia,
      Methylobacterium sp. and M. mucogenicum biofilms were strongly inhibited by crude
      cell-free supernatants from the other bacteria. The crude cell-free supernatants
      of M. mucogenicum and S. capsulata demonstrated a high potential for inhibiting
      the growth of counterpart biofilms. Multispecies biofilm formation was strongly
      inhibited in the absence of A. calcoaceticus. Only crude cell-free supernatants
      produced by B. cepacia and A. calcoaceticus had no inhibitory effects on
      multispecies biofilm formation, while metabolite molecules of M. mucogenicum
      showed the most significant biocontrol potential.

PMID- 21732714
TI  - Hippocampal synaptic plasticity in Alzheimer's disease: what have we learned so
      far from transgenic models?
AB  - Transgenic (Tg) mouse models of Alzheimer's disease (AD) are used to investigate
      mechanisms underlying disease pathology and identify therapeutic strategies. Most
      Tg AD models, which at least partly recapitulate the AD phenotype, are based on
      insertion of one or more human mutations (identified in Familial AD) into the
      mouse genome, with the notable exception of the anti-NGF mouse, which is based on
      the cholinergic unbalance hypothesis. It has recently emerged that impaired
      hippocampal synaptic function is an early detectable pathological alteration,
      well before the advanced stage of amyloid plaque accumulation and general cell
      death. Nevertheless, electrophysiological studies performed on different Tg
      models or on the same model by different research groups have yielded contrasting
      results. We therefore summarized data from original research papers studying
      hippocampal synaptic function using electrophysiology, to review what we have
      learned so far. We analyzed results obtained using the following Tg models: (1)
      single/multiple APP mutations; (2) single presenilin (PS) mutations; (3) APPxPS1
      mutations; (4) APPxPS1xtau mutations (3xTg); and (5) anti-NGF expressing (AD11)
      mice. We observed that the majority of papers focus on excitatory basic
      transmission and long-term potentiation, while few studies evaluate inhibitory
      transmission and long-term depression. We searched for common synaptic
      alterations in the various models that might underlie the memory deficits
      observed in these mice. We also considered experimental variables that could
      explain differences in the reported results and briefly discuss successful rescue
      strategies. These analyses should prove useful for future design of
      electrophysiology experiments to assess hippocampal function in AD mouse models.

PMID- 21732715
TI  - Surface acoustic waves increase the susceptibility of Pseudomonas aeruginosa
      biofilms to antibiotic treatment.
AB  - Bacterial urinary tract infections resulting from prolonged patient
      catheterization have become a major health problem. One of the major issues is
      bacterial resistance to antibiotic treatments due to biofilm formation inside the
      catheters, thus enhancing the search for alternative treatments. In the present
      study, a device containing a piezo element capable of transmitting low-frequency
      surface acoustic waves (SAW) onto the indwelling catheter was used. The SAW were
      able to eradicate biofilm-residing bacteria by >85% when applied simultaneously
      with an antibiotic in three clinically relevant species, viz. Escherichia coli,
      Staphylococcus epidermidis and Pseudomonas aeruginosa. Moreover, transcriptome
      analysis revealed that SAW can alter the transcription pattern of P. aeruginosa,
      suggesting that this signal can be specifically sensed by the bacterium.

PMID- 21732716
TI  - Influence of gender on receipt of guideline-based antiretroviral therapy in the
      era of HAART.
AB  - United States HIV guidelines delineate preferred antiretroviral treatment (ART)
      and discourage use of sub-potent, toxic, or adversely interacting combinations.
      It is unclear how often patients receive guideline concordant ART and what
      factors are correlated with receiving guideline-inconsistent ART. The objective
      of this study was to assess ART reported by participants of the Women's
      Interagency HIV Study (WIHS) and the Multicenter AIDS Cohort Study (MACS) to
      determine whether gender is associated with receipt of guideline-inconsistent
      ART. ART reported by WIHS and MACS participants from 1 January 2001, to 31
      December 2007, was assessed for concordance with HIV guidelines. Logistic
      regression with generalized estimating equations estimated the crude and adjusted
      odds ratios and 95% confidence intervals associated with guideline-inconsistent
      regimens. Of 2937 participants, 463 subjects (WIHS n = 263; MACS n = 200)
      reported guideline-inconsistent ART during the study period. Age > 50 years (aOR
      = 2.22, 95% CI 1.14, 4.33) and HIV-1 RNA (aOR = 1.17, 95% CI 1.08, 1.25) but not
      participant gender (aOR = 1.21, 95% CI 0.88, 1.65) were associated with guideline
      inconsistent ART. The prevalence of guideline-inconsistent ART peaked in 2004;
      however, there was not a statistically significant increase or decrease over
      time. Guideline-inconsistent ART was not related to gender, but was often used by
      older patients and patients with higher viral loads. Monitoring ART quality based
      on concordance with expert guidelines could improve treatment outcomes in a
      substantial number of patients.

PMID- 21732717
TI  - Mito-communications.

PMID- 21732718
TI  - Mitochondrial genome sequence of the Tibetan wild ass (Equus kiang).
AB  - The Tibetan wild ass, or kiang (Equus kiang) is endemic to the cold and hypoxic
      (4000-7000 m above sea level) climates of the montane and alpine grasslands of
      the Tibetan Plateau. We report here the complete nucleotide sequence of the E.
      kiang mitochondrial genome. Our results show that E. kiang mitochondrial DNA is
      16,634 bp long, and predicted to encode all the 37 genes that are typical for
      vertebrates.

PMID- 21732719
TI  - DNA barcoding of an invasive mammal species, the small Indian mongoose (Herpestes
      javanicus; E. Geoffroy Saint-Hillaire 1818) in the Caribbean and Hawaiian
      Islands.
AB  - BACKGROUND AND AIM: The use of DNA barcodes has been proposed as a promising tool
      for identifying species. The efficacy of this tool for invasive species requires
      further exploration. The species status of the small Indian mongoose, an exotic
      invasive in several parts of the world, has been contentious due to morphological
      similarity with its congeners in its natural habitat. Although the small Indian
      mongoose is recognized as Herpestes javanicus, this nomenclature has been used
      interchangeably with Herpestes auropunctatus. MATERIALS AND METHODS: Here, we
      demonstrate the utility of using DNA barcoding approaches with mtDNA cytochrome b
      to discriminate between the two species and other sympatric members of the genus
      Herpestes (Herpestes naso, Herpestes urva, and Herpestes edwardsii). Using the
      diagnostic DNA positions we obtain, we can identity specimens of nonnative
      populations of the small Indian mongoose from the Caribbean and Hawaiian Islands
      to their species of origin. RESULTS: A singe diagnostic site accomplishes the
      identification of H. javanicus versus H. auropunctatus. CONCLUSION: Our results
      indicate that the nonnative mongoose populations from the Caribbean and Hawaiian
      Islands are H. auropunctatus, and not H. javanicus.

PMID- 21732720
TI  - Investigation of DNA binding mechanism, photoinduced cleavage activity,
      electrochemical properties and biological functions of mixed ligand copper(II)
      complexes with benzimidazole derivatives: synthesis and spectral
      characterization.
AB  - The benzimidazole derivative Schiff bases and their copper(II) (Cu(II)) mixed
      polypyridyl complexes (1-4) have been synthesized and characterized by the
      spectral and analytical techniques. DNA binding/cleavage studies indicate a
      stronger binding capability for the complex 4 which is confirmed by the
      absorbance, viscometric and gel-electrophoresis studies. The photocleavage of
      plasmid pBR322 DNA reveals that hydroxyl radical (OH(*)) and singlet oxygen
      ((1)O(2)) are likely to be the reactive species. Analysis of the growth activity
      shows that the antimicrobial effect of these Schiff bases on Gram-negative
      bacteria is higher than that on Gram-positive. Furthermore, the complexes having
      nitro group show an increased antimicrobial effect.

PMID- 21732721
TI  - Constituents with tyrosinase inhibitory activities from branches of Ficus erecta
      var. sieboldii King.
AB  - Phytochemical investigation of the branches of Ficus erecta var. sieboldii King
      resulted in the isolation of eight constituents: p-hydroxybenzoic acid (1),
      methyl p-hydroxybenzoate (2), vanillic acid (3), methyl vanillate (4), syringic
      acid (5), beta-sitosterol (6), alpha-amyrin acetate (7), and ethyl linoleate (8).
      Their chemical structures were identified via spectroscopic means as well as by
      comparing their data with literature values. Studies on tyrosinase inhibition
      activities were conducted for the isolated compounds. Among them, p
      hydroxybenzoic acid (1) and methyl p-hydroxybenzoate (2) were identified as
      active tyrosinase inhibitors with IC(50) values of 0.98 +/- 0.042 and 0.66 +/-
      0.025 mM, respectively, showing comparable activities to that of arbutin (IC(50)
      = 0.32 +/- 0.015 mM), a standard control. Inhibition kinetics, as analyzed by
      Lineweaver-Burk plots, indicated that compounds 1 and 2 were competitive
      inhibitors of diphenolase of mushroom tyrosinase. Notably, isolated compounds 1-8
      were reported for the first time as constituents of F. erecta.

PMID- 21732722
TI  - Interprofessional education for interprofessional practice about patients'
      decision support/patients' decision aids.

PMID- 21732723
TI  - Development and validation of the interprofessional collaborator assessment
      rubric (ICAR).
AB  - There have been increasing calls for a competency-based approach in
      interprofessional education (IPE). The purpose of this multi-site research
      project was to develop a validated set of interprofessional collaborator
      competencies and an associated competency-based assessment rubric, in both
      English and French languages. The first phase involved a detailed comparative
      analysis of peer-reviewed and grey literature using typological analysis to
      construct a draft list of interprofessional collaborator competency categories
      and statements. A two-round Delphi survey of experts was undertaken to validate
      these competencies. In the second phase, an assessment rubric was developed based
      on the validated competencies and then evaluated for utility, clarity,
      practicality and fairness through multi-site focus groups with students and
      faculty at both college and university levels. The paper outlines an approach to
      developing, constructing and validating a bilingual instrument for
      interprofessional learning and assessment. The approach was collaborative in
      nature, involving an interprofessional project team and respondents from across
      multiple health profession education programs. The Delphi survey ratings indicate
      a high level of agreement with the importance of the competency statements and
      focus group participants rated the rubric positively and felt it had value. The
      focus group results were also useful in pre-piloting the contextual application
      of the instrument across multiple health profession education programs. This
      rubric instrument may be used across a variety of professions and learning
      contexts. Future work includes evaluation of further dimensions of validity and
      reliability for this tool across a variety of settings.

PMID- 21732724
TI  - Interprofessional professionalism: linking professionalism and interprofessional
      care.

PMID- 21732725
TI  - Workshop report: European workshop on ataxia-telangiectasia, Frankfurt, 2011.
AB  - Ataxia-telangiectasia (A-T) is a devastating human recessive disorder
      characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal
      instability, and cancer susceptibility. The European Workshop on Ataxia
      Telangiectasia 2011 in Frankfurt focused on status quo of patient care and future
      clinical research directions. In Europe, approximately 600 patients are
      registered and many national websites have been established. During the meeting,
      guidelines of patient care were discussed and all participants agreed to build up
      an European A-T research network in near future to bring basic research and new
      therapies into clinical applications.

PMID- 21732726
TI  - Activation of the nuclear factor kappaB pathway by heavy ion beams of different
      linear energy transfer.
AB  - PURPOSE: Risk assessment of radiation exposure during long-term space missions
      requires the knowledge of the relative biological effectiveness (RBE) of space
      radiation components. Few data on gene transcription activation by different
      heavy ions are available, suggesting a dependence on linear energy transfer. The
      transcription factor Nuclear Factor kappaB (NF-kappaB) can be involved in
      cancerogenesis. Therefore, NF-kappaB activation by accelerated heavy ions of
      different linear energy transfer (LET) was correlated to survival. MATERIALS AND
      METHODS: NF-kappaB-dependent gene induction after exposure to heavy ions was
      detected in stably transfected human embryonic kidney 293 cells (HEK-pNF-kappaB
      d2EGFP/Neo cells carrying a neomycin resistance), using the destabilized Enhanced
      Green Fluorescent Protein (d2EGFP) as reporter. RESULTS: Argon (LET 272 keV/MUm)
      and neon ions (LET 91 keV/MUm) had the highest potential to activate NF-kappaB,
      resulting in a RBE of 8.9 in comparison to 150 kV X-rays. The RBE for survival
      also reached its maximum in this LET range, with a maximal value of 2.
      CONCLUSIONS: NF-kappaB might be involved in modulating survival responses of
      cells hit by heavy ions in the LET range of 91-272 keV/MUm and could therefore
      become a factor to be considered for risk assessment of radiation exposure during
      space travel.

PMID- 21732727
TI  - Configuration interaction calculations of cross sections for proton stopping
      reactions.
AB  - PURPOSE: To illustrate the role of quantum mechanical electronic structure
      methods in providing accurate predictions of the cross sections for ionization
      and electron capture processes that occur as a result of proton collisions in the
      high-eV to low-keV energy region. METHODS: Calculations are carried out to
      compute potential curves and non-adiabatic coupling elements for a variety of
      collision partners employing the ab initio multireference single- and double
      excitation configuration interaction (MRD-CI) method. These results are used as
      input for the electronic-state close-coupling (ESCC) method in order to compute
      cross sections for various transitions that occur because of collisions. RESULTS:
      Emphasis is placed on proton-molecule collisions that play a key role in various
      medical applications as well as in astrophysics and nano-scale materials
      manufacturing. Examples discussed include the Na-He pair of atoms of interest in
      recent astrophysical observations, proton collisions with various hydrocarbons
      and also with water and oxygen, and key ionic products such as H(2)O(+) and
      H(3)O(+) . CONCLUSIONS: The computed cross sections provide a detailed picture of
      radiation damage dynamics in Monte Carlo simulations. This information can
      potentially enhance the efficiency of proton beam focusing and also reduce
      undesirable side effects on body tissues.

PMID- 21732728
TI  - Enhancement of bioconversion efficiency of limonin by Pseudmonas putida G7.
AB  - The biocatalytic activity of periplasmic dehydrogenase of Pseudomonas putida G7
      strain to catalyse limonin was enhanced when whole cells were permeabilized with
      EDTA (1 MUM) lysozyme (100 MUg/ml). The treated cells were entrapped in dialysis
      membranes to increase the stability. Permeabilized cells (1 g dry weight)
      entrapped in dialysis membrane could biotransform 73.67% of limonin in
      unpasteurized mandarin juices in a single-batch cycle of 3 h. Furthermore,
      permeabilized cells stored for 45 days in phosphate buffered saline (at 4 or 30
      degrees C) retained enzyme activity and were reusable for up to eight batch
      cycles of limonin reduction. The results of this study suggest a potential
      application of permeabilized P. putida G7 cells for reducing limonin levels in
      mandarin juices.

PMID- 21732729
TI  - Fabrication of capillary-like network in a matrix of water-soluble polymer using
      poly(methyl methacrylate) microfibers.
AB  - Poly(methyl methacrylate) (PMMA) microfibers were used as a template for
      development of a capillary-like network in agarose hydrogel. Microfibers with
      diameter 10-20 MUm, which is comparable to the diameter of native capillary
      vessels, were fabricated using a wet spinning technique. The microfibers were
      embedded in agarose gel and dissolved by immersing the gel in dichloromethane.
      The resultant microchannels in the gel had the same diameter as the microfibers,
      and allowed an aqueous solution to be perfused through the gel. The methodology
      is promising for fabricating a capillary-like network in tissue engineering
      scaffolds of various water-soluble polymers.

PMID- 21732730
TI  - Presence of retinopathy in type 1 diabetic patients is associated with
      subclinical macroangiopathy.
AB  - PURPOSE: The aim of the study was to assess the relationships between diabetic
      retinopathy, subclinical atherosclerosis and wave reflection in type 1 diabetic
      patients. METHODS: The investigation involved 87 type 1 diabetic patients aged 34
      years (interquartile range [IQR]: 29-43), with a disease duration of 10 years
      (IQR: 9-14). Of these 39 (45%) had diabetic retinopathy. Carotid intima-media
      thickness (CIMT) was measured using high resolution ultrasonography. Wave
      reflection and central hemodynamics [central (CAI(x)) and peripheral augmentation
      index (PAI(x))] were determined with the use of tonometry. RESULTS: Patients with
      retinopathy compared to those without had increased CIMT (530 vs 480 MUm, p =
      0.017) and wave reflection (CAI(x) [118.90 vs 110.96 %, p = 0.03] and PAI(x)
      [64.95 vs 57.44 %, p = 0.029]). In logistic regression analysis, patient's age,
      duration of diabetes, systolic and diastolic blood pressure, postprandial
      glycemia, HbA1c value, CIMT (p = 0.017), CAI(x) (p = 0.03) and PAI(x) (p = 0.016)
      were associated with the presence of diabetic retinopathy. However, in the
      multivariate model, CIMT and CAI(x) did not remain predictors of retinopathy.
      CONCLUSIONS: We have shown that the presence of retinopathy in type 1 diabetic
      patients is associated with subclinical atherosclerosis and wave reflection.

PMID- 21732731
TI  - Effects of the transcutaneous electrode temperature on the accuracy of
      transcutaneous carbon dioxide tension.
AB  - AIM: The harmful effect of hypocapnia on the neonatal brain emphasizes the
      importance of monitoring arterial carbon dioxide tension (PaCO2). Transcutaneous
      monitoring of carbon dioxide (tcPCO2) reduces the need for arterial blood
      sampling. Drawbacks are high electrode temperature causing risks of skin burning.
      The aim was to determine the accuracy and precision of tcPCO2 at reduced
      electrode temperature. METHODS: Forty newborns (GA 24.9-41.7) were included. Two
      tc-monitors were applied (TCM4, Radiometer, Copenhagen). Arterial blood gas
      sampling and monitoring of tcPCO2-level at different electrode temperatures was
      done simultaneously (39 degrees C, 40 degrees C, 41 degrees C, 42 degrees C, 44
      degrees C). Difference of PaCO2 - tcPCO2 was expressed as a percentage of the
      mean. RESULTS: Mean PaCO2 was 5.8kPa [3,2; 7.9]. Bias (PaCO2 - tcPCO2) increased
      from 5% at 44 degrees C to 17% at 39 degrees C, but did not differ significantly
      between 41 degrees C and 40 degrees C. The precision of the tcPCO2 at each
      temperature ranged from +7-10%. After correction for the temperature-dependent
      overreading, we found increasing PaCO2 - tcPCO2 difference with increasing PaCO2,
      approx. 2% pr. kPa increase of CO(2). Only mild transient erythema was observed.
      CONCLUSION: A lower electrode temperature in tcPCO2-monitoring increases
      systematic overreading of the tc-electrode. However, in very preterm babies,
      monitoring at 40 degrees C or 41 degrees C is possible provided a bias correction
      of 12-15% is applied.

PMID- 21732732
TI  - Changing incidence and subtypes of ALS in Modena, Italy: A 10-years prospective
      study.
AB  - We performed a prospective population-based study to describe the temporal
      pattern of the incidence and prevalence and the clinical features and phenotypes
      of ALS in Modena, Italy, from 2000 to 2009. From 2000 onwards, a prospective
      registry has been collecting all cases of incident ALS among residents in the
      province of Modena. This source was implemented by cases resulting from the
      provincial hospitals, and by death certificates. Based on 193 newly diagnosed
      cases, the crude average annual incidence rate of ALS was 2.9 cases per 100,000
      person years (py); adjusted incidence rate was 2.8/100,000. The age-standardized
      incidence rates increased from 2.6 per 100,000 py in 2000-2004 to 2.9 per 100,000
      py in 2005-2009, representing an annual increase of approximately 2% throughout
      the 10-year period. There was a constant increase in prevalence rates throughout
      the years of the study (from 5.8/100,000 on 31 December 2000 to 11.2/100,000 on
      31 December 2009). Median life time was 29 months for patients diagnosed before
      the year 2000 and 36 months for patients diagnosed from 1 January 2000 (p <
      0.01). Thus, we report incidence rates similar to those reported by recent
      European population based studies, but we observed an increasing trend over the
      10 years of the study. The increasing incidence is not explained by aging of the
      population, and our study raises the question as to whether local environmental
      or genetic factors are driving this temporal trend. Along with an increasing
      incidence, we found an important increase in prevalence and survival probably
      related to access to mutidisciplinary clinics and improvements in symptomatic
      care of ALS.

PMID- 21732733
TI  - Reduced deactivation in reward circuitry and midline structures during emotion
      processing in borderline personality disorder.
AB  - OBJECTIVES. Borderline personality disorder (BPD) is characterized by a pervasive
      affective dysregulation. While recent imaging studies demonstrated the neural
      correlates of abnormal emotion processing in BPD and recently one study reported
      alterations of the reward circuit in this patient group, the exact neural
      mechanisms underlying the impact of abnormal emotion on reward behavior remain
      unclear. METHODS. We therefore conducted an fMRI study in healthy controls and
      BPD patients to investigate the modulation of the anticipation of reward by
      simultaneously presented emotional pictures. RESULTS. BPD patients revealed a
      disturbed differentiation between reward and non-reward anticipation in the
      bilateral pregenual anterior cingulate cortex if a positive or negative emotional
      picture is presented simultaneously. In the ventral striatum and the bilateral
      ventral tegmental area, BPD patients and healthy controls are able to
      differentiate between reward and non-reward even under emotional stimulation, but
      BPD patients show a reduced deactivation in the above mentioned regions compared
      to healthy controls. CONCLUSIONS. Altered emotion processing in BPD patients is
      likely to affect the reward system. More basic deficits in reward circuitry and
      other midline regions' level of resting state activity may contribute to this
      effect.

PMID- 21732734
TI  - Credibility of low-strength static magnet therapy as an attention control
      intervention for a randomized controlled study of CranioSacral therapy for
      migraine headaches.
AB  - BACKGROUND: Developing valid control groups that generate similar perceptions and
      expectations to experimental complementary and alternative (CAM) treatments can
      be challenging. The perceived credibility of treatment and outcome expectancy
      often contributes to positive clinical responses to CAM therapies, thereby
      confounding efficacy data. As part of a clinical feasibility study, credibility
      and expectancy data were obtained from subjects suffering from migraine who
      received either CranioSacral therapy (CST) or an attention-control, sham, and low
      strength magnet (LSSM) intervention. OBJECTIVE: The objective of this study was
      to evaluate whether the LSSM intervention generated similar levels of subject
      credibility and expectancy compared to CST. DESIGN: This was a two-arm randomized
      controlled trial. SUBJECTS: Sixty-five (65) adults with moderate to severe
      migraine were the subjects of this study. INTERVENTIONS: After an 8-week
      baseline, subjects were randomized to eight weekly treatments of either CST
      (n=36) or LSSM (n=29). The latter involved the use of a magnet-treatment protocol
      using inactive and low-strength static magnets designed to mimic the CST protocol
      in terms of setting, visit timing, body positioning, and therapist-subject
      interaction. OUTCOME MEASURES: A four-item, self-administered
      credibility/expectancy questionnaire, based on a validated instrument, was
      completed after the first visit. RESULTS: Using a 0-9 rating scale, the mean
      score for perceived logicality of treatment was significantly less for LSSM
      (5.03, standard deviation [SD] 2.34) compared to CST (6.64, SD 2.19). Subject
      confidence that migraine would improve was greater for CST (5.94, SD 2.01) than
      for LSSM (4.9, SD 2.21), a difference that was not statistically significant.
      Significantly more subjects receiving CST (6.08, SD 2.27) would confidently
      recommend treatment to a friend than those receiving LSSM (4.69, SD 2.49).
      CONCLUSIONS: Although LSSM did not achieve a comparable level of credibility and
      expectancy to the CST, several design and implementation factors may have
      contributed to the disparity. Based on analysis of these factors, the design and
      implementation of a future study may be improved.

PMID- 21732735
TI  - College students' Facebook stalking of ex-partners.
AB  - There are abundant anecdotes and warnings of inappropriate behaviors on social
      networking sites, particularly about Facebook. The purpose of the present study
      was to examine whether individuals obsessively monitor or harass their ex
      partners on Facebook (related to general "Facebook stalking") and, if so, whether
      those individuals would also engage in cyber obsessional pursuit (COP) and
      obsessive relational pursuit (ORI), which are categories of cyberstalking and
      stalking. A total of 411 valid participants answered questions about the ways
      they communicated with their ex-romantic partners using Facebook, resulting in
      three factors: Covert Provocation, Public Harassment, and Venting. Each category
      of Facebook harassment was related to perpetration of COP and ORI. Additionally,
      participants who engaged in COP were almost six times more likely to also
      perpetrate ORI. If participants admitted to engaging in some types of stalking
      behaviors, they did so online, offline, and on Facebook. Implications for social
      networking site usage and stalking laws are discussed. There is a kernel of truth
      to the popular term "Facebook stalking."

PMID- 21732736
TI  - Mutations in the rrs A1401G gene and phenotypic resistance to amikacin and
      capreomycin in Mycobacterium tuberculosis.
AB  - The aminoglycosides amikacin (AMK)/kanamycin (KAN) and the cyclic polypeptide
      capreomycin (CAP) are important injectable drugs in the treatment of multidrug
      resistant tuberculosis. Cross-resistance among these drug classes occurs and
      information on the minimum inhibitory concentrations (MICs), above the normal
      wild-type distribution, may be useful in identifying isolates that are still
      accessible to drug treatment. Isolates from the Eastern Cape Province of South
      Africa were subjected to DNA sequencing of the rrs (1400-1500 region) and tlyA
      genes. Sequencing data were compared with (i) conventional susceptibility testing
      at standard critical concentrations (CCs) on Middlebrook 7H11 agar and (ii) MGIT
      960-based MIC determinations to assess the presence of AMK- and CAP-resistant
      mutants. Isolates with an rrs A1401G mutation showed high-level resistance to AMK
      (>20 mg/L) and decreased phenotypic susceptibility to CAP (MICs 10-15 mg/L). The
      MICs of CAP were below the bioavailability of the drug, which suggests that it
      may still be effective against multi- or extensively drug resistant tuberculosis
      [M(X)DR-TB]. Agar-based CC testing was found to be unreliable for resistance
      recognition of CAP in particular.

PMID- 21732737
TI  - Synthesis, characterization, nucleic acid binding, and cytotoxic activity of a
      Ru(II) polypyridyl complex.
AB  - The binding properties of [Ru(bpy)(2)(H(2)IIP)](2+) (1) {bpy=2,2'-bipyridine,
      H(2)IIP=2-(indole-3-yl)-imidazolo[4,5-f][1,10]phenanthroline} with calf thymus
      DNA (CT-DNA) and yeast tRNA have been investigated comparatively by different
      spectroscopic and viscosity measurements. The results suggest that the affinity
      of complex 1 binding with yeast tRNA is stronger than that of complex 1 binding
      with CT-DNA, and complex 1 is a better enantioselective binder to yeast tRNA than
      to CT-DNA. The toxicity of complex 1 was concentration dependent, and HL-60 cells
      are more sensitive to complex 1 than Hep-G2 cells; complex 1 could induce Hep-G2
      cell apoptosis.

PMID- 21732738
TI  - Perinatal depressive symptoms in HIV-infected versus HIV-uninfected women: a
      prospective study from preconception to postpartum.
AB  - OBJECTIVE: Depression is common among HIV-infected women, predicts treatment
      nonadherence, and consequently may impact vertical transmission of HIV. We report
      findings from a study evaluating preconception, pregnancy, and postpartum
      depressive symptoms in HIV-infected vs. at-risk, HIV-uninfected women. METHODS:
      We examined the prevalence and predictors of elevated perinatal (i.e., pregnancy
      and/or postpartum) depressive symptoms using a Center for Epidemiological Studies
      Depression (CES-D) scale score of >=16 in 139 HIV-infected and 105 HIV-uninfected
      women (62% African American) from the Women's Interagency HIV Study (WIHS).
      RESULTS: The prevalence of elevated perinatal depressive symptoms did not differ
      by HIV serostatus (HIV-infected 44%, HIV-uninfected 50%, p=0.44). Among HIV
      infected women, the strongest predictor of elevated symptoms was preconception
      depression (odds ratio [OR] 5.71, 95% confidence interval [CI] 2.67-12.19,
      p<0.001); crack, cocaine, and/or heroin use during preconception was marginally
      significant (OR 3.10, 95% CI 0.96-10.01, p=0.06). In the overall sample,
      additional significant predictors of perinatal depression included having
      multiple sex partners preconception (OR 2.20, 95% CI 1.12-4.32, p=0.02), use of
      preconception mental health services (OR 2.51, 95% CI 1.03-6.13, p=0.04), and not
      graduating from high school (OR 1.92, 95% CI 1.06-3.46, p=0.03). CONCLUSIONS:
      Elevated perinatal depressive symptoms are common among HIV-infected and at-risk
      HIV-uninfected women. Depressive symptoms before pregnancy were the strongest
      predictor of perinatal symptoms. Findings underscore the importance of early and
      ongoing assessment and treatment to ensure low vertical transmission rates and
      improving postpregnancy outcomes for mothers and children.

PMID- 21732739
TI  - Pregnancy outcome in women following splenectomy.
AB  - OBJECTIVE: To investigate pregnancy outcome of patients following splenectomy.
      METHODS: A retrospective study comparing pregnancies of women who have and have
      not undergone splenectomy was performed. The study investigated a select
      population representing the south of Israel. Women lacking antenatal care as well
      as those having multiple gestations were excluded from the analysis. Stratified
      analysis, using a multiple logistic regression model, was performed to control
      for confounders. RESULTS: During the study period, there were 219,656 deliveries,
      of which 150 occurred in women who underwent splenectomy. Postsplenectomy women
      tended to be older, were more likely to be Jewish, and had a lower number of
      deliveries and an earlier gestational age at delivery. Higher rates of fertility
      treatment, previous cesarean delivery, and severe preeclampsia were found among
      postsplenectomy women. In addition, splenectomy was significantly associated with
      pregnancy and labor complications, such as cesarean delivery, pneumonia during
      pregnancy, and complications of anesthesia and sedation during labor. Using a
      multivariate analysis with backward elimination, the following conditions were
      independently associated with splenectomy: previous cesarean delivery (odds ratio
      [OR] 1.5, 95% confidence interval [CI] 1.1-2.3, p=0.039), fertility treatment (OR
      2.6, 95% CI 1.3-5.4, p=0.008), preterm delivery (OR 1.9, 95% CI 1.3-3.1,
      p=0.003), and maternal age (OR 1.04, 95% CI 1.015-1.07, p=0.002). After
      controlling for possible confounders by using another multivariate analysis with
      preterm delivery as the outcome variable, splenectomy was found to be an
      independent risk factor for preterm delivery (OR 2.1, 95% CI 1.4-3.3, p=0.001).
      CONCLUSION: Splenectomy is an independent risk factor for preterm delivery.

PMID- 21732740
TI  - Biomechanical comparison of two different collar structured implants supporting 3
      unit fixed partial denture: a 3-D FEM study.
AB  - OBJECTIVE: The purpose of the study was to compare the effects of two distinct
      collar geometries of implants on stress distribution in the bone as well as in
      the fixture-abutment complex, in the framework and in the veneering material of 3
      unit fixed partial denture (FPD). MATERIAL AND METHODS: The 3-dimensional finite
      element analysis method was selected to evaluate the stress distribution in the
      system composed of 3-unit FPD supported by two different dental implant systems
      with two distinct collar geometries; microthread collar structure (MCS) and non
      microthread collar structure (NMCS). In separate load cases, 300 N vertical, 150
      N oblique and 60 N horizontal, forces were utilized to simulate the
      multidirectional chewing forces. Tensile and compressive stress values in the
      cortical and cancellous bone and von Mises stresses in the fixture-abutment
      complex, in the framework and veneering material, were simulated as a body and
      investigated separately. RESULTS: In the cortical bone lower stress values were
      found in the MCS model, when compared with NMCS. In the cancellous bone, lower
      stress values were observed in the NMCS model when compared with MCS. In the
      implant-abutment complex, highest von Mises stress values were noted in the NMCS
      model; however, in the framework and veneering material, highest stress values
      were calculated in MCS model. CONCLUSIONS: MCS implants when compared with NMCS
      implants supporting 3-unit FPDs decrease the stress values in the cortical bone
      and implant-abutment complex. The results of the present study will be evaluated
      as a base for our ongoing FEA studies focused on stress distribution around the
      microthread and non-microthread collar geometries with various prosthesis design.

PMID- 21732741
TI  - Site-to-site variation of muscle activity and sensitivity in the human anterior
      temporalis muscle: implications for contingent stimulation.
AB  - OBJECTIVE: To evaluate variation of electromyographic (EMG) activity and
      sensitivity between different sites of anterior temporalis (AT) muscle. MATERIALS
      AND METHODS: Sixteen healthy subjects (eight men: 28.8 +/- 5.2 year old and eight
      women: 29.1 +/- 3.9) participated in one experimental session. EMG activity
      during masticatory muscle contraction was recorded from nine sites at the AT
      muscle in a 3 * 3 grid with 1 cm between. The subjects maintained steady 30% of
      maximal voluntary contraction (MVC) using visual feedback. The surface EMG
      electrode was moved sequentially between these nine test sites and the
      contractions were repeated. One site was tested four times to assess test-re-test
      variability. The sensory threshold to electrical stimulation and impedance was
      also measured at the same sites as the placement of EMG electrodes. RESULTS: The
      30% MVC force values did not differ between sites (p = 0.863) or within the same
      site (p = 0.995) due to the feedback. The EMG activity during 30% MVC was highest
      at the anterior-superior site (p < 0.05) with a marginal difference within the
      same site (p = 0.044). Impedance was higher at the posterior-superior, posterior
      middle and posterior-inferior sites (p < 0.05). The sensory threshold was highest
      at the posterior-superior site (p < 0.05). CONCLUSION: These findings showed that
      electrodes close to the hairline have higher impedance and sensory thresholds and
      should be avoided. The anterior-superior site produces the highest EMG activity
      and lower sensory thresholds and can be recommended as the optimal site to place
      the electrode for contingent stimulation.

PMID- 21732742
TI  - Nuclear MASPIN expression relates to a better prognosis in elderly patients with
      laryngeal carcinoma.
AB  - CONCLUSION: MASPIN subcellular location can be considered a prognostic marker
      that is potentially useful for identifying elderly patients with laryngeal
      carcinoma at higher risk of early loco-regional recurrence, who may benefit from
      more aggressive therapy. In a targeted treatment setting, re-activated nuclear
      MASPIN in combination with anti-angiogenic and/or cytotoxic drugs may be
      effective in treating laryngeal carcinoma in elderly patients. OBJECTIVES: Aging
      is associated with molecular, cellular, and physiological changes that influence
      carcinogenesis and cancer growth. MASPIN has multifaceted anti-tumor effects and
      available evidence supports the hypothesis that its subcellular location
      influences its functions. The aim of the present study was to firstly assess the
      potential prognostic role of subcellular MASPIN location in elderly patients (>65
      years old) with laryngeal carcinoma. METHODS: MASPIN expression and location were
      immunohistochemically determined in 68 consecutive elderly patients with
      laryngeal carcinoma. RESULTS: Nodal involvement and pathological stage correlated
      strongly with the prognosis for laryngeal carcinomas in elderly patients, in
      terms of disease recurrence rate and disease-free survival. The loco-regional
      recurrence rate was significantly lower (p = 0.041) and the disease-free survival
      after treatment was significantly longer (p = 0.045) in cases with a nuclear
      pattern of MASPIN subcellular expression.

PMID- 21732743
TI  - Vocal fold wound healing after injection of human adipose-derived stem cells in a
      rabbit model.
AB  - CONCLUSION: Injection of injured rabbit vocal folds with human adipose-derived
      stem cells (hADSCs) led to improved wound healing and fewer signs of scarring as
      demonstrated by a decreased collagen content in the treated folds compared with
      the untreated folds. hADSCs remained viable for up to 12 weeks in rabbit vocal
      folds. OBJECTIVE: The aim of this study was to investigate the morphologic and
      histologic properties of scarred rabbit vocal folds following injection of
      hADSCs. METHODS: This was a randomized, controlled animal study. Twenty-four
      vocal folds from 12 New Zealand rabbits were scarred using a CO(2) laser and
      injected with either hADSCs (left vocal fold) or phosphate-buffered saline (right
      vocal fold). Every 4 weeks for the first 12 weeks after injection, an endoscopic
      examination was performed to assess the morphology of the vocal folds. Twelve
      weeks later the animals were euthanized and the tissues were stained for
      histology. RESULTS: In comparison with the right vocal folds, there was
      significantly less granulation tissue in the hADSCs-injected left vocal folds (p
      < 0.05). Histological examination revealed excessive collagen deposition and
      perichondral fibrosis in the right vocal folds, whereas the left vocal folds
      exhibited better wound healing and less collagen deposition (p < 0.05). Among the
      12 specimens injected with hADSCs, 4 specimens demonstrated viable hADSCs under
      immunofluorescent cytochemistry.

PMID- 21732744
TI  - Contrast enhancement of the inner ear after intravenous administration of a
      standard or double dose of gadolinium contrast agents.
AB  - CONCLUSION: Imaging of the endolymphatic space was possible in most cases after
      administering a standard dose of gadolinium (Gd) by using heavily T2-weighted 3D
      fluid-attenuated inversion recovery (hT(2)W-3D-FLAIR) magnetic resonance imaging
      (MRI). OBJECTIVES: The aim of this study was to characterize the contrast
      enhancement in the inner ear after intravenous injection of Gd and to compare the
      signal intensity after a double dose or standard dose of Gd. METHODS: We injected
      a standard dose of gadodiamide hydrate (DTPA-BMA) or a double dose of gadoteridol
      (HP-DO3A) intravenously in patients affected by Meniere's disease and performed
      hT(2)W-3D-FLAIR 3 T MRI. Contrast enhancement of the basal turn of the cochlea
      was evaluated semiquantitatively. RESULTS: Endolymphatic hydrops was observed in
      the cochlea and vestibule of the affected ears of patients with Meniere's disease
      in both the double-dose group and the standard-dose group.

PMID- 21732745
TI  - The challenge and importance of standardizing pre-analytical variables in
      surgical pathology specimens for clinical care and translational research.
AB  - The introduction of targeted cancer therapies into clinical practice, in which
      patients are selected for novel treatments based on results of companion
      molecular testing of their tumor specimens, has created significant new
      challenges for the surgical pathology laboratory. These include standardization
      of tissue handling and sample preparation with accurate documentation to ensure
      optimal quality of clinical samples to reduce the risk of errors in molecular
      biology tests. The assay of tumor tissues for biomarkers that can provide
      predictive data for prognosis or treatment should enable selection of the most
      appropriate therapies (Yaziji et al. 2008, Hicks and Kulkarni 2008). Major
      advances have been made in the ability to profile clinical samples for research
      at the DNA, RNA and protein levels. To translate this new information into the
      clinical setting, however, the quality of the starting material, in this case the
      tumor tissue, determines the accuracy and reliability of companion diagnostic
      assay results and therefore optimal therapeutic strategies. Inaccurate results
      owing to compromised tissue quality can lead to false positive or false negative
      results with therapeutic consequences that can harm patients and affect their
      eventual outcome.

PMID- 21732746
TI  - Optimizing the use and applications of special stains: clinical and experimental
      approaches.

PMID- 21732747
TI  - Detection of Histoplasma capsulatum DNA in peripheral blood from a patient with
      ocular histoplasmosis syndrome.
AB  - Ocular histoplasmosis syndrome (OHS) is a significant cause of vision loss in
      young and middle-aged adults. We report here a case of an immunocompetent 37-year
      old man who presented fever, malaise, headache, and anterior cervical
      lymphadenopathy for one week, after which he started to experience a sudden loss
      in visual acuity of his right eye. Fluorescent angiography and an optical
      coherent tomography demonstrated the presence of a type II choroidal neo-vascular
      membrane in the right eye, suggesting a diagnosis of OHS. A peripheral blood
      sample was tested by nested PCR to detect Histoplasma capsulatum using a set of
      primers known to amplify a DNA sequence coding for a specific 100-kDa protein of
      this fungus (Hc100-PCR). The blood sample was Hc100-PCR-positive and sequence
      analysis showed an identity of 97% with the reference sequence. The patient
      received intravitreal bevacizumab injection and itraconazol therapy, leading to
      an improvement in media vision acuity. In this case, the molecular test provided
      evidence linking the ocular lesions with an earlier infection by H. capsulatum
      and demonstrated that the Hc100-nested PCR assay is a valuable tool in the
      diagnosis of histoplasmosis.

PMID- 21732748
TI  - Absence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii
      isolated from Swedish patients.
AB  - Pneumocystis jirovecii remains an important cause of pneumonia in the
      immunocompromised host, with the largest group of patients at risk for P.
      jirovecii pneumonia (PCP) in Sweden being those with haematological diseases.
      Widespread prophylaxis and treatment for P. jirovecii with sulfa-containing drugs
      have effectively decreased the incidence of PCP, but concerns have been raised
      about the possible emergence of P. jirovecii isolates that are resistant to these
      drugs. Two point mutations in the gene coding for the dihydropteroate synthase
      enzyme (DHPS) in P. jirovecii have been shown to be associated with prior
      exposure to sulfa drugs. We retrospectively studied the occurrence of P.
      jirovecii DHPS mutations in isolates recovered from 103 Swedish patients. The
      DHPS gene, including the polymorphic positions 165 and 171, were amplified and
      sequenced by pyrosequencing technology. All the clinical specimens showed a wild
      type pattern indicating that the occurrence of P. jirovecii DHPS mutations in
      Sweden is very low or absent.

PMID- 21732750
TI  - Endotoxin exposure and childhood wheeze and asthma: a meta-analysis of
      observational studies.
AB  - BACKGROUND: Exposure to endotoxin has been widely investigated as a potential
      factor for asthma and associated symptoms in children with different results. To
      clarify a potential relationship, we performed the present meta-analysis to
      integrate the results of studies examining the association of endotoxin exposure
      with wheeze and asthma in children. METHODS: A search for relevant studies and
      reviews was conducted in MEDLINE, Highwire, CINAHL, and The Cochrane Library
      databases. Adjusted odds ratio (OR) with corresponding 95% confidence interval
      (CI) for endotoxin exposure and wheeze or asthma were retrieved and pooled to
      generate summary effect estimates in STATA 11.1. RESULTS: Nineteen studies were
      included in the meta-analysis. The summary estimates suggested that endotoxin was
      positively associated with wheeze in infants and toddlers (meta-OR: 1.48, 95% CI:
      1.10-1.98), but negatively related to asthma in school-aged children (meta-OR:
      0.82, 95% CI: 0.69-0.97 for endotoxin concentration and 0.68, 95% CI: 0.50-0.93
      for endotoxin load). CONCLUSIONS: Based on the studies evaluated, endotoxin is a
      risk factor for wheeze in younger children, but a protective factor for asthma in
      older children. Thus, this study supports the "hygiene hypothesis."

PMID- 21732751
TI  - Could precision-engineered peptide epitopes/vaccines be the key to a cancer cure?

PMID- 21732753
TI  - Afatinib (BIBW 2992) development in non-small-cell lung cancer.
AB  - Afatinib (BIBW 2992), a novel aniline-quinazoline derivative, irreversibly and
      equipotently targets the intrinsic kinase activity of all active ErbB receptor
      family members. Preclinical results show that afatinib is effective in lung
      cancer models, including those with EGF receptor (EGFR) mutations resistant to
      reversible first-generation EGFR inhibitors. Afatinib is being investigated in
      the LUX-Lung program, which will evaluate afatinib as a first-line treatment in
      patients with EGFR-activating mutations (LUX-Lung 2, 3 and 6) and as a second- or
      third-line treatment in patients that have acquired resistance to gefitinib
      and/or erlotinib (LUX-Lung 1, 4 and 5). LUX-Lung 1 and 2 have demonstrated,
      within their respective target groups, a significant increase in the disease
      control rate of 58 and 86%, respectively, and significant prolongation of
      progression-free survival. Further Phase III clinical trials are currently
      ongoing to assess afatinib in combination with paclitaxel (LUX-Lung 5), and
      compared with cisplatin/pemetrexed (LUX-Lung 3) or cisplatin/gemcitabine (LUX
      Lung 6).

PMID- 21732754
TI  - Ridaforolimus: a promising drug in the treatment of soft-tissue sarcoma and other
      malignancies.
AB  - Ridaforolimus (deforolimus; AP23573; MK-8669) is a novel sirolimus derivative
      manufactured by ARIAD Pharmaceuticals and acquired by Merck. It is a small
      molecule kinase inhibitor of the mTOR in clinical development for the treatment
      of cancer. Both intravenous and oral formulations of the agent are being tested
      in cancer clinical trials. In preclinical and clinical studies, ridaforolimus
      exhibited significant antitumor activity with acceptable safety and tolerability.
      With single-agent ridaforolimus, mucositis and myelosuppression were dose
      limiting toxicities. In advanced soft-tissue sarcoma, single-agent ridaforolimus
      was associated with a 29% clinical benefit rate and 2% partial response rate. A
      Phase III trial has recently been reported to have met its primary end point.

PMID- 21732755
TI  - When tumor cells make blood vessels: implications for glioblastoma therapy.
AB  - The paper by Soda et al. provides experimental evidence for the plasticity of
      glioblasoma multiforme (GBM) cells, specifically their ability to form vascular
      endothelial cells (ECs). The study demonstrates the existence of tumor-derived
      ECs (TDECs) in GBM blood vessels of transgenic mice and humans. Blood vessels
      with TDECs were functional and were more frequently found in hypoxic tumor
      regions. In vitro hypoxic conditions enhanced the transition of tumor-initiating
      cells to an endothelial-like morphology and the formation of tube-like
      structures. Contrary to normal ECs, TDECs did not express VEGF receptors, and
      treatment of experimental GBM tumors with anti-VEGF/VEGF receptor agents led to
      an increase in the proportion of TDECs relative to normal ECs. These findings
      identify a new potential mechanism of resistance of GBM tumors to anti-VEGF
      therapies. Future strategies for GBM therapy will likely require the combined
      targeting of normal ECs and TDECs, as well as the development of strategies that
      prevent the conversion of tumor cells into vascular ECs.

PMID- 21732756
TI  - Negative regulation of mTORC2 by glycogen synthase kinase-3beta: an adaptive
      process to stress with an anticancer therapeutic potential?
AB  - Exposure of cells to hormones, mitogens and growth factors can lead to the
      activation of PI3K and serine-threonine kinase Akt/PKB. Akt is recruited to the
      plasma membrane, a process that facilitates its phosphorylation at threonine 308
      and serine (S)473 mediated by the PI3K-dependent kinase 1 and mTORC2 kinase,
      respectively. Active Akt has several targets, one of the most important being
      mTORC1, which is essential for stimulation of protein synthesis and cell growth.
      Active Akt phosphorylates the alpha- and beta-isoforms of glycogen synthase
      kinase 3 (GSK-3), leading to the inhibition of GSK-3 activity and phosphorylation
      of proteins with key roles in cell proliferation and metabolism. Akt activity is
      induced in response to various forms of stress, mainly to facilitate cell
      survival and maintain cell proliferation. Recent work by Chen and colleagues has
      placed GSK-3beta in a negative regulatory loop resulting in Akt inactivation. GSK
      3beta carries out this function via the phosphorylation of the mTORC2 component
      protein rictor at S1235, a modification that compromises the ability of mTORC2 to
      induce Akt activity by phosphorylation at S473. Rictor phosphorylation at S1235
      can be detected in proliferating cells, but it can be particularly induced in
      cells exposed to endoplasmic reticulum stress. Rictor S1235 phosphorylation
      decreases the tumorigenic properties of activated Ras, providing evidence for a
      link between the GSK-3beta-mTORC2 axis and tumorigenesis. A part of its potential
      role in regulating metabolic processes associated with endoplasmic reticulum
      stress, an interesting question is whether disruption of the GSK-3beta-mTORC2 arm
      would have any implications in tumor formation and treatment.

PMID- 21732757
TI  - Organ-specific markers in circulating tumor cell screening: an early indicator of
      metastasis-capable malignancy.
AB  - Circulating tumor cells (CTCs) represent an important biological link in the
      spread of primary solid tumors to the metastatic disease responsible for most
      cancer mortality. Their detection in the peripheral blood of patients with many
      different carcinomas has shown that tumor-cell dissemination can proceed at an
      early stage of tumor development and their presence is associated with poor
      clinical outcomes, particularly in metastatic disease. In this article we
      describe how the increasingly sensitive isolation and detailed molecular
      characterization of CTCs has greatly improved our understanding of metastatic
      proliferation. We focus on how CTC detection and knowledge of the molecular
      architecture of these cells can serve as biomarkers to signal metastasis-capable
      disseminating cells and predict therapy-specific response. This has marked
      clinical utility for improved selection of systemic therapies to the individual
      needs of a cancer patient, real-time monitoring of metastatic disease treatments
      and the development of new targeted therapies.

PMID- 21732758
TI  - A new frontier in personalized cancer therapy: mapping molecular changes.
AB  - Mutations in the genome of a normal cell can affect the function of its many
      genes and pathways. These alterations could eventually transform the cell from a
      normal to a malignant state by allowing an uncontrolled proliferation of the cell
      and formation of a cancer tumor. Each tumor in an individual patient can have
      hundreds of mutated genes and perturbed pathways. Cancers clinically presenting
      as the same type or subtype could potentially be very different at the molecular
      level and thus behave differently in response to therapy. The challenge is to
      distinguish the key mutations driving the cancer from the background of
      mutational noise and find ways to effectively target them. The promise is that
      such a molecular approach to classifying cancer will lead to better diagnostic,
      prognostic and personalized treatment strategies. This article provides an
      overview of advances in the molecular characterization of cancers and their
      applications in therapy.

PMID- 21732759
TI  - Somatostatin receptors in non-neuroendocrine malignancies: the potential role of
      somatostatin analogs in solid tumors.
AB  - Somatostatin receptors (sstrs) are G-protein-coupled receptors that mediate
      various physiological effects when activated by the neuropeptide somatostatin or
      its synthetic analogs. In addition to the well-documented antisecretory effects
      of sstr(2)-preferential somatostatin analogs octreotide and lanreotide, ligand
      binding to sstr initiates an inhibitory action on tumor growth. This effect may
      result from both indirect actions (suppression of growth factors and growth
      promoting hormones [e.g., GH/IGF-1 axis] and inhibition of angiogenesis) and
      direct actions (activation of antigrowth activities [e.g., apoptosis]). As solid
      tumor cells express multiple sstrs, there is a rationale to evaluate the
      potential antitumor effects of pasireotide (SOM230), a multireceptor-targeted
      somatostatin analog with high binding affinity for sstr(1-3) and sstr(5).
      Pasireotide reduces systemic IGF-1 levels more potently than currently available
      somatostatin analogs and has been well tolerated in clinical trials.

PMID- 21732760
TI  - Emerging radiation techniques for early-stage breast cancer after breast
      conserving surgery.
AB  - Standard whole-breast irradiation consisting of a dose of 45-50 Gy over 5 weeks
      with or without the addition of a boost to the tumor bed has equivalent survival
      to mastectomy and is considered to be the standard of care for most patients with
      early-stage breast cancer. Newer techniques have been developed to shorten the
      course of radiation or limit normal tissue exposure in an attempt to increase
      accessibility to and tolerance of radiation therapy. This article will review
      some of the newer regimens and techniques for treating early-stage breast cancer
      after breast-conserving surgery.

PMID- 21732762
TI  - Demonstration of a sex difference in the predictability of widths of unerupted
      permanent canines and premolars in a Japanese population.
AB  - OBJECTIVES: (1) To identify any differences in the accuracy of the prediction of
      the summed widths of unerupted permanent canines and premolars for males vs
      females and, if differences are identified, (2) to examine the sex differences in
      the best combination of independent variables and (3) to evaluate the practical
      accuracy using our models for both sexes, respectively. MATERIALS AND METHODS:
      Records for 200 orthodontic patients (100 males and 100 females) with discernible
      tooth crowding in the permanent dentition were selected. Mesiodistal tooth crown
      widths, dental arch widths, and basal arch lengths were measured. Predicted sum
      widths of permanent canines and premolars in both dental arches were calculated
      using stepwise regression analysis. RESULTS: Among male subjects, the best
      combinations of independent variables were the widths of the upper central and
      lateral incisors (U1, U2) and the first molar (U6) for the maxilla (R(2) = 0.615)
      and the mandible, lower central and lateral incisors (L1, L2), and the first
      molar (L6) (R(2) = 0.685), whereas in females, the best combinations for
      prediction were found to be U1, U2, U6, and the maxillary arch width for the
      maxilla (R(2) = 0.429) and L1, L2, L6, and the basal arch length for the mandible
      (R(2) = 0.426). Correlation coefficients between each independent and dependent
      variable in the female subject group were found to be weaker than those for the
      male subject group. CONCLUSIONS: We found the sex differences in the accuracy of
      prediction and the best combination of independent variables for predicting the
      summed widths of unerupted canines and premolars. These new models should be
      clinically useful, providing highly accurate prediction.

PMID- 21732763
TI  - Free-radical scavenger edaravone treatment confers neuroprotection against
      traumatic brain injury in rats.
AB  - Traumatic brain injury (TBI) is one of the leading causes of neurological
      disability in young adults. Edaravone, a novel synthetic small-molecule free
      radical scavenger, has been shown to have a neuroprotective effect in both animal
      models of cerebral ischemia and stroke patients; however, the underlying
      mechanism is poorly understood. In this report, we investigated the potential
      mechanisms of edaravone treatment in a rat model of TBI. TBI was induced in the
      right cerebral cortex of male adult rats using Feeney's weight-drop method.
      Edaravone (0.75, 1.5, or 3 mg/kg) or vehicle (normal saline) was intravenously
      administered at 2 and 12 h after TBI. Edaravone treatment significantly decreased
      hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal
      programmed cell death compared to vehicle treatment. The protective effects of
      edaravone treatment were also related to the pathology of TBI on non-neuronal
      cells, as edaravone decreased astrocyte and glial activation. Lastly, edaravone
      treatment significantly reduced the presence of inflammatory cytokines, cerebral
      edema, blood-brain barrier (BBB) permeability, and, importantly, neurological
      deficits following TBI. Our results suggest that edaravone exerts a
      neuroprotective effect in the rat model of TBI. The likely mechanism is via
      inhibiting oxidative stress, leading to a decreased inflammatory response and
      glial activation, and thereby reducing neuronal death and improving neurological
      function.

PMID- 21732764
TI  - Mild stretch-induced injury increases susceptibility to interleukin-1beta-induced
      release of matrix metalloproteinase-9 from astrocytes.
AB  - Traumatic brain injury (TBI) results in the activation of glia and the release of
      proinflammatory cytokines, including interleukin (IL)-1beta. The response of
      astrocytes to mild TBI has not been well studied. We used an in vitro model of
      cell stretch to investigate the effects of mild mechanical insult on astrocyte
      injury (lactate dehydrogenase and propidium iodide), and on mediators of
      inflammation including IL-1beta, the chemokine CX3CL1, and nitrite. Here, we
      tested the hypothesis that a mild mechanical insult would increase susceptibility
      of astrocytes to delayed exposure to IL-1beta, including enhanced release of the
      matrix metalloproteinease-9 (MMP-9). We investigated the role of the mitogen
      protein-activated kinase (MAPK) pathway in these responses. Cells subjected to a
      mild stretch show an increase in activation of the ERK1/2 and JNK pathways, and
      an increase in lactate dehydrogenase (LDH), but no change in the levels of
      inflammatory mediators. An early increase in LDH was dependent on ERK activation.
      Exposure to IL-1beta, or to stretch alone, did not increase MMP-9. In contrast,
      the combination of mild stretch followed by IL-1beta resulted in greater
      activation of the ERK pathway compared to either stimulus alone, and also
      resulted in an increase in the production of MMP-9 by astrocytes. Inhibition of
      the ERK pathway suppressed the increase in MMP-9 induced by the combination of
      stretch and IL-1beta treatment. These results suggest that a primary mild
      mechanical injury renders astrocytes more susceptible to a secondary exposure to
      a proinflammatory cytokine such as IL-1beta via the activation of the ERK
      pathway, and suggest a mechanism by which a mild head injury may confer increased
      susceptibility to neurologic injury caused by a subsequent insult.

PMID- 21732765
TI  - Natural history of headache after traumatic brain injury.
AB  - Headache is one of the most common persisting symptoms after traumatic brain
      injury (TBI). Yet there is a paucity of prospective longitudinal studies of the
      incidence and prevalence of headache in a sample with a range of injury severity.
      We sought to describe the natural history of headache in the first year after
      TBI, and to determine the roles of prior history of headache, sex, and severity
      of TBI as risk factors for post-traumatic headache. A cohort of 452 acute,
      consecutive patients admitted to inpatient rehabilitation services with TBI were
      enrolled during their inpatient rehabilitation from February 2008 to June 2009.
      Subjects were enrolled across 7 acute rehabilitation centers designated as TBI
      Model Systems centers. They were prospectively assessed by structured interviews
      prior to inpatient rehabilitation discharge, and at 3, 6, and 12 months after
      injury. Results of this natural history study suggest that 71% of participants
      reported headache during the first year after injury. The prevalence of headache
      remained high over the first year, with more than 41% of participants reporting
      headache at 3, 6, and 12 months post-injury. Persons with a pre-injury history of
      headache (p<0.001) and females (p<0.01) were significantly more likely to report
      headache. The incidence of headache had no relation to TBI severity (p=0.67).
      Overall, headache is common in the first year after TBI, independent of the
      severity of injury range examined in this study. Use of the International
      Classification of Headache Disorders criteria requiring onset of headache within
      1 week of injury underestimates rates of post-traumatic headache. Better
      understanding of the natural history of headache including timing, type, and risk
      factors should aid in the design of treatment studies to prevent or reduce the
      chronicity of headache and its disruptive effects on quality of life.

PMID- 21732766
TI  - Immunological aspects of allogeneic and autologous mesenchymal stem cell
      therapies.
AB  - Mesenchymal stem cells (MSCs) have potential for therapeutic application as an
      immunomodulatory and regenerative agent. The immunogenicity and survival of MSCs
      after infusion are, however, not clear and evidence suggests that allogeneic but
      also autologous MSCs disappear rapidly after infusion. This may be associated
      with the susceptibility of MSCs to lysis by natural killer (NK) cells, possibly a
      result of culture-induced stress. In the present study we examined whether NK
      cell-mediated lysis of MSCs could be inhibited by immunosuppressive drugs. Human
      MSCs were isolated from adipose tissue and expanded in culture. Peripheral blood
      mononuclear cells were activated with interleukin (IL)-2 (200 U/ml) and IL-15 (10
      ng/ml) for 7 days. CD3(-)CD16(+)CD56(+) NK cells were then isolated by
      fluorescence-activated cell sorting and added to europium-labeled MSCs for 4 hr
      in the presence or absence of immunosuppressive drugs. Lysis of MSCs was
      determined by spectrophotometric measurement of europium release. Nonactivated NK
      cells were not capable of lysing MSCs. Cytokine-activated NK cells showed
      upregulated levels of granzyme B and perforin and efficiently lysed allogeneic
      and autologous MSCs. Addition of tacrolimus, rapamycin or sotrastaurin to the
      lysis assay did not inhibit MSC killing. Furthermore, preincubation of activated
      NK cells with the immunosuppressive drugs for 24 hr before exposure to MSCs had
      no effect on MSC lysis. Last, addition of the immunosuppressants before and
      during the activation of NK cells, reduced NK cell numbers but did not affect
      their capacity to lyse MSCs. We conclude that the immunosuppressive drugs
      tacrolimus, rapamycin, and sotrastaurin are not capable of inhibiting the lysis
      of allogeneic and autologous MSCs by activated NK cells. Other approaches to
      controlling lysis of MSCs should be investigated, as controlling lysis may
      determine the efficacy of MSC therapy.

PMID- 21732767
TI  - The pathologist: part of the team.

PMID- 21732768
TI  - Melanocytic lesions: current state of knowledge--part III.

PMID- 21732769
TI  - An update on reporting histopathologic prognostic factors in melanoma.
AB  - CONTEXT: Accurate diagnosis of melanocytic lesions is essential for the adequate
      clinical management of patients. Thus, thorough reporting of histopathologic
      parameters, especially in the initial biopsies, is a critical component of both
      diagnosis and staging. OBJECTIVE: To review current data on histopathologic
      prognostic factors for melanoma, with special emphasis on their use and
      applicability to clinical practice. Special attention is focused on the criteria
      highlighted by the new 2009 version of The American Joint Committee on Cancer
      (AJCC) system of melanoma staging and classification. DATA SOURCES: Published
      peer-reviewed literature and personal experience of the authors. CONCLUSIONS:
      When reporting melanoma, we recommend that a template be provided, including all
      the histologic parameters that have been proved significant in determining the
      tumor staging and prognosis of a patient. The template may also include other
      details that may be helpful in further analysis of potential complete excisional
      biopsies or metastatic lesions, such as predominant type of tumor cells, presence
      or absence of desmoplastic component, or associated benign melanocytic lesions.
      Although there are several drawbacks in reporting some of these histopathologic
      parameters (interobserver variability, occasional lack of a perfectly
      reproducible method for quantifying these criteria), we suggest that at least the
      essential histopathologic parameters highlighted by the newest version of the
      AJCC system for melanoma staging and classification should be included in the
      report.

PMID- 21732770
TI  - Update on fluorescence in situ hybridization in melanoma: state of the art.
AB  - CONTEXT: Recent advances in understanding the molecular basis of melanoma have
      resulted in development of fluorescence in situ hybridization (FISH) protocols
      designed to detect genetic abnormalities discriminating melanoma from nevi. The
      most extensively studied is a 4-probe multicolor FISH probe panel targeting
      chromosomes 6 and 11. Validation studies showed promising sensitivity and
      specificity for distinguishing benign nevi and malignant melanoma by FISH. Recent
      studies show that a melanoma FISH assay has great potential for becoming an
      important diagnostic adjunct in classification of melanocytic lesions and in
      diagnosis of melanoma. OBJECTIVE: To present a comprehensive review of the
      science and practical aspects of FISH in melanoma for pathologists considering
      the use of melanoma FISH in their practice. DATA SOURCES: Review of the
      literature and personal experience of the authors. CONCLUSIONS: Judicious use of
      a 4-probe multicolor melanoma FISH procedure can enhance accuracy for diagnosis
      of melanoma and improve classification of melanocytic proliferations.

PMID- 21732771
TI  - Lentigo maligna: melanoma in situ on chronically sun-damaged skin.
AB  - CONTEXT: Cutaneous primary invasive malignant melanoma often is classified by its
      histologic appearance. Major recognized histologic subtypes of melanoma include
      superficial spreading, lentigo maligna melanoma, nodular, and acral lentiginous.
      More recently, it has been shown that most primary invasive melanomas harbor
      nonrandom genetic or biochemical aberrations that correlate with anatomic site or
      with the amount of cutaneous exposure to sunlight. It also is generally accepted
      that most primary invasive melanomas are preceded by an intraepidermal atypical
      melanocytic proliferation that lacks invasive capability (melanoma in situ).
      OBJECTIVE: To focus on lentigo maligna, the preinvasive/in situ form of melanoma
      located on chronically sun-damaged skin. DATA SOURCES: Review of the literature
      and the authors' personal experiences. CONCLUSIONS: A better understanding of the
      earliest stage of melanoma progression, including the contribution of chronic
      exposure to ultraviolet radiation, may lead to improved classification schemes
      that direct more effective targeted or personalized therapies for patients.

PMID- 21732772
TI  - The recurrent nevus phenomenon: a history of challenge, controversy, and
      discovery.
AB  - CONTEXT: The diagnosis of recurrent nevus poses a potential challenge to
      practicing pathologists. Although most recurrent nevi show uniform microscopic
      findings and pose no great diagnostic difficulty, a few cases exhibit some
      histopathologic features similar to, and in some cases indistinguishable from,
      melanoma. Historically, the term pseudomelanoma has been used in the literature
      to describe such recurrent nevi, although this label has the potential for
      confusion and is no longer the favored term for recurrent pigmented melanocytic
      nevi. OBJECTIVE: To describe historical, histopathologic, and immunohistochemical
      features of recurrent pigmented melanocytic nevi and to review briefly the
      literature surrounding the mechanism of recurrence. DATA SOURCES: Published peer
      reviewed literature and the authors' personal experience. CONCLUSIONS:
      Recognition of the histopathologic pattern of recurrent nevi leads the
      pathologist to the correct diagnosis in most cases; however, in particularly
      challenging specimens or in circumstances in which there is insufficient clinical
      history, immunohistochemical studies have proved helpful in distinguishing
      recurrent nevi from melanoma.

PMID- 21732773
TI  - Acral junctional nevus versus acral lentiginous melanoma in situ: a differential
      diagnosis that should be based on clinicopathologic correlation.
AB  - CONTEXT: Acral lentiginous melanoma is the most prevalent clinical presentation
      of melanoma in ethnic groups other than whites and also occurs in significant
      numbers in North America and Europe. Despite a clear-cut clinical picture,
      histologic findings seen in partial biopsies may be too subtle and deceive
      pathologists dealing with such cases. OBJECTIVES: To make pathologists aware of
      the histologic findings during early phases of acral lentiginous melanoma
      (including the in situ phase), to compare those findings with what is seen in
      acral junctional nevus, and to highlight their similarities and differences. This
      review will also emphasize the important clinical and dermatoscopic findings to
      be considered when diagnosing acral lentiginous melanoma. DATA SOURCES: Review of
      published articles on the epidemiology; the clinical, dermatoscopic, and
      histopathologic findings; and the molecular biology of acral lentiginous melanoma
      as well as the personal experience of the authors when dealing with such cases.
      CONCLUSIONS: Acral lentiginous melanoma is a clinicopathologic entity with a
      clear-cut clinical picture: a diameter larger than 0.7 mm; ill-defined, darkly
      pigmented, flat lesion with irregular borders on acral locations; and the
      presence of mostly single-cell proliferations of melanocytes along the dermo
      epidermal junction. Along with a few additional criteria, these findings should
      be sufficient to allow the pathologist to make the diagnosis and to recommend
      complete excision. Fluent communication between clinician and pathologist will
      facilitate a correct diagnosis.

PMID- 21732774
TI  - Immunohistochemistry of melanocytic proliferations.
AB  - CONTEXT: Histologic analysis allows accurate classification of most melanocytic
      lesions as benign or malignant. Only in a minority of lesions is it necessary to
      use other techniques as an aid in the diagnosis. Among them, most authors
      recommend immunohistochemistry. OBJECTIVE: To describe how to apply
      immunohistochemistry to particular differential diagnoses and the potential
      pitfalls. DATA SOURCES: Personal experience and review of literature.
      CONCLUSIONS: There is no single marker, or combination thereof, that establishes
      an unequivocal diagnosis of melanoma or nevus. Thus it is necessary to carefully
      analyze the pattern of expression (patchy versus diffuse) and localization
      (maturation) in the context of morphologic standard features.

PMID- 21732775
TI  - Molecular diagnostics in melanoma: current status and perspectives.
AB  - CONTEXT: In the current "molecular" era, the advent of technology, such as array
      based platforms, systems biology, and genome-wide approaches, has made it
      possible to examine human cancers, including melanoma, for genetic mutations,
      deletions, amplification, differentially regulated genes, and epigenetic changes.
      Advancement in current technologies is such that one can now examine ribonucleic
      acid (RNA), deoxyribonucleic acid (DNA), and protein directly from the patient's
      own tumor. OBJECTIVE: To apply these new technologies in advancing molecular
      diagnostics in melanoma has historically suffered from a major obstacle, namely,
      the scarcity of fresh frozen, morphologically defined tumor banks, annotated with
      clinical information. Recently, some of the new platforms have advanced to permit
      utilization of formalin-fixed, paraffin-embedded (FFPE) tumor specimens as
      starting material. DATA SOURCES: This article reviews the latest technologies
      applied to FFPE melanoma sections, narrowing its focus on the utility of
      transcriptional profiling, especially for melastatin; comparative genomic
      hybridization; BRAF and NRAS mutational analysis; and micro ribonucleic acid
      profiling. CONCLUSION: New molecular approaches are emerging and are likely to
      improve the classification of melanocytic neoplasms.

PMID- 21732776
TI  - Are there barriers to the release of paraffin blocks for clinical research
      trials? A College of American Pathologists survey of 609 laboratories.
AB  - CONTEXT: The number of paraffin blocks submitted for patients enrolled in
      clinical research trials appears to be declining. OBJECTIVE: To obtain
      information on laboratory policies and procedures in complying with requests to
      submit paraffin blocks for research. DESIGN: A questionnaire was sent to members
      of a voluntary market research panel composed of pathologists representing a
      broad spectrum of experience and practice settings. The questions addressed
      departmental policies and the likely responses to requests to submit pathology
      materials for patients enrolled in clinical trials. RESULTS: The survey was
      completed by 609 of 762 pathologists (80%) who responded to the invitation. More
      than 90% of respondents stated that they comply with these requests. Although 14%
      have a policy precluding the release of blocks for research, 84% of those will
      send limited tissue samples in lieu of blocks. When tumor is confined to a single
      block, most laboratories will not release the block but will send unstained
      slides. Very few laboratories require reimbursement before releasing tissues.
      CONCLUSIONS: Pathologists attempt to comply with requests for materials but
      usually refuse to release the only diagnostic paraffin block so that materials
      are retained for possible future needs. Other problems identified in this survey
      include difficulties in getting blocks returned when needed and poor
      communication between researchers and laboratories. Lack of reimbursement and
      inadequate consent are not significant barriers to release of materials.

PMID- 21732777
TI  - Development of an evidence-based approach to external quality assurance for
      breast cancer hormone receptor immunohistochemistry: comparison of reference
      values.
AB  - CONTEXT: External quality assurance and proficiency testing programs for breast
      cancer predictive biomarkers are based largely on traditional ad hoc design; at
      present there is no universal consensus on definition of a standard reference
      value for samples used in external quality assurance programs. OBJECTIVE: To
      explore reference values for estrogen receptor and progesterone receptor
      immunohistochemistry in order to develop an evidence-based analytic platform for
      external quality assurance. DESIGN: There were 31 participating laboratories, 4
      of which were previously designated as "expert" laboratories. Each participant
      tested a tissue microarray slide with 44 breast carcinomas for estrogen receptor
      and progesterone receptor and submitted it to the Canadian Immunohistochemistry
      Quality Control Program for analysis. Nuclear staining in 1% or more of the tumor
      cells was a positive score. Five methods for determining reference values were
      compared. RESULTS: All reference values showed 100% agreement for estrogen
      receptor and progesterone receptor scores, when indeterminate results were
      excluded. Individual laboratory performance (agreement rates, test sensitivity,
      test specificity, positive predictive value, negative predictive value, and kappa
      value) was very similar for all reference values. Identification of suboptimal
      performance by all methods was identical for 30 of 31 laboratories. Estrogen
      receptor assessment of 1 laboratory was discordant: agreement was less than 90%
      for 3 of 5 reference values and greater than 90% with the use of 2 other
      reference values. CONCLUSIONS: Various reference values provide equivalent
      laboratory rating. In addition to descriptive feedback, our approach allows
      calculation of technical test sensitivity and specificity, positive and negative
      predictive values, agreement rates, and kappa values to guide corrective actions.

PMID- 21732778
TI  - Aberrant protein expression and promoter methylation of p16 gene are correlated
      with malignant transformation of salivary pleomorphic adenoma.
AB  - CONTEXT: The significance of promoter methylation of the p16 gene and
      intracellular localization of p16 protein in the carcinogenesis of salivary
      carcinoma ex pleomorphic adenoma (Ca-ex-PA) is not clear. The correlation of the
      promoter methylation of the p16 gene and the expression and localization of p16
      protein in Ca-ex-PA need to be further clarified. OBJECTIVE: To investigate the
      p16 protein expression and promoter methylation of p16 gene in Ca-ex-PA and their
      roles in the malignant transformation of pleomorphic adenoma to Ca-ex-PA. DESIGN:
      The p16 protein expression and promoter methylation of the p16 gene were
      determined in both benign and malignant components of 50 primary salivary Ca-ex
      PA tissues by immunohistochemistry and methylation-specific polymerase chain
      reaction. Expression of p16 protein and promoter methylation of the p16 gene
      between the benign and the malignant components was compared statistically.
      RESULTS: The tumor cells in the malignant components showed significantly higher
      p16 protein expression in the cytoplasm and lower expression in the nuclei than
      those in the benign components. Promoter methylation frequency of the p16 gene in
      the malignant components (36%) was significantly higher than that in the benign
      components (16%). There were no correlations between p16 protein expression and
      promoter methylation of the p16 gene in either benign or malignant components.
      CONCLUSIONS: Overexpression of p16 protein in the cytoplasm and decreased
      expression of p16 protein in the nucleus may play important roles in the
      evolution of pleomorphic adenoma to Ca-ex-PA. Promoter methylation of the p16
      gene may be correlated with the malignant transformation of pleomorphic adenoma.

PMID- 21732779
TI  - Recurrence risk and margin status in granular cell tumors of the breast: a
      clinicopathologic study of 13 patients.
AB  - CONTEXT: Granular cell tumors (GCTs) of the breast are rare neoplasms that mimic
      epithelial malignancy clinically and rarely occur in association with it.
      Granular cell tumors of the breast are not infrequently excised with positive
      margins. Reports describing risk of recurrence including data on margin status
      and follow-up are lacking. OBJECTIVE: To review our series of GCTs of the breast
      to determine the risk of recurrence if excised with positive or close margins.
      DESIGN: Cases of GCT of the breast were reviewed. Margin status of specimens was
      recorded as positive, close (<1 mm), and negative. RESULTS: Thirteen female
      patients with GCT of the breast were identified. Mean patient age at presentation
      was 45 years. Seventy-seven percent of patients were African American and 23%
      were white. African American patients presented on average 13 years earlier than
      white patients. Average tumor size was 1.22 cm. Fifteen percent of lesions had
      positive margins on excisional biopsy or lumpectomy and 31% had tumor cells
      within 1 mm of the margin. One of 13 patients (8%) had coexistent invasive ductal
      carcinoma. Average follow-up for the entire group was 77 months. Patients with
      positive margins remained free of tumor progression or recurrence for 89 months
      and patients with close margins also remained disease free during a 64-month
      follow-up period. No tumors recurred out of the entire group. CONCLUSION:
      Granular cell tumors of the breast have little long-term risk for recurrence,
      even when excised with positive margins. Surgical evaluation after nonexcisional
      biopsy may still be indicated to assess for the possible association of
      colocalized carcinoma.

PMID- 21732780
TI  - Trainable immunohistochemical HER2/neu image analysis: a multisite performance
      study using 260 breast tissue specimens.
AB  - CONTEXT: Aperio Technologies, Inc (Vista, California) provides a new
      immunohistochemistry (IHC) HER2 Image Analysis (IA) system that allows tuning of
      the intensity thresholds of the HER2/ neu scoring scheme to adapt to the staining
      characteristics of different reagents. OBJECTIVE: To compare the trainable IHC
      HER2 IA system for different reagents to conventional manual microscopy (MM) in a
      multisite study. DESIGN: Two hundred sixty formalin-fixed, paraffin-embedded
      breast cancer specimens from 3 clinical sites were assayed: 180 specimens stained
      with Dako's HercepTest (Carpinteria, California), and 80 specimens stained with
      Ventana's PATHWAY HER-2/neu (Tucson, California). At each site, 3 pathologists
      performed a blinded reading of the glass slides with the use of a light
      microscope. The glass slides were then scanned and after a wash-out period and
      randomization, the same pathologists outlined a representative set of tumor
      regions to be analyzed by IHC HER2 IA. Each of the methods, MM and IA, was
      evaluated separately and comparatively by using kappa statistics of negative
      HER2/neu scores (0, 1+) versus equivocal HER2/neu scores (2+) versus positive
      HER2/neu scores (3+) among the different pathologists. RESULTS: kappa Values for
      IA and MM were obtained across all sites. MM: 0.565-0.864; IA: 0.895-0.947; MM
      versus IA: 0.683-0.892 for site 1; MM: 0.771-0.837; IA: 0.726-0.917; MM versus
      IA: 0.687-0.877 for site 2; MM: 0.463-0.674; IA: 0.864-0.918; MM versus IA: 0.497
      0.626 for site 3. CONCLUSION: Aperio's trainable IHC HER2 IA system shows
      substantial equivalence to MM for Dako's HercepTest and Ventana's PATHWAY HER
      2/neu at 3 clinical sites. Image analysis improved interpathologist agreement in
      the different clinical sites.

PMID- 21732781
TI  - Expression of AIF and HtrA2/Omi in small lymphocytic lymphoma and diffuse large B
      cell lymphoma.
AB  - CONTEXT: The pathogenesis of non-Hodgkin lymphoma may involve deregulation of
      apoptosis. In response to apoptotic stimuli, several proapoptotic proteins are
      released into the cytoplasm from the mitochondria, including second mitochondria
      derived activator of caspases/direct inhibitor of apoptosis protein binding
      protein with low p I (Smac/DIABLO), apoptosis-inducing factor (AIF), and high
      temperature requirement protein A2 (HtrA2/Omi). Apoptosis-inducing factor
      promotes apoptosis through a caspase-independent pathway, while Smac/DIABLO and
      HtrA2/Omi do so through both caspase-dependent and caspase-independent pathways.
      Smac/DIABLO was reported to be strongly positive in diffuse large B-cell lymphoma
      (DLBCL) and virtually absent in small lymphocytic lymphoma/chronic lymphocytic
      leukemia (SLL/CLL). Little is known about the expression of AIF and HtrA2/Omi in
      lymphomas. OBJECTIVE: To evaluate the expression of AIF and HtrA2/Omi in SLL and
      DLBCL. DESIGN: Twenty-three DLBCLs, 20 SLLs/CLLs, and 10 benign lymph nodes were
      evaluated for AIF and HtrA2/Omi expression by immunohistochemical staining.
      RESULTS: Apoptosis-inducing factor was strongly and diffusely expressed in 19 of
      23 (83%) cases of DLBCL with comparable expression pattern between germinal
      center-like and non-germinal center-like subgroups. Apoptosis-inducing factor was
      weakly positive in 15 of 20 (75%) cases of SLL/CLL with increased intensity in
      pseudofollicles. In contrast, HtrA2/Omi was weakly expressed in SLL/CLL (17 of
      20; 85%) and DLBCL (18 of 23; 78%). CONCLUSIONS: The different expression level
      and pattern of AIF and HtrA2/Omi in SLL/CLL and DLBCL may suggest different
      apoptotic mechanisms involved in the pathogenesis and prognosis of these
      diseases. HtrA2/Omi does not appear to be a major player in the regulation of
      apoptosis of DLBCL and SLL/CLL.

PMID- 21732782
TI  - CD34+ cell enumeration by flow cytometry: a comparison of systems and
      methodologies.
AB  - CONTEXT: An increasing number of medical centers can collect bone marrow,
      peripheral blood, or umbilical cord stem cells. Pathology laboratories should
      accommodate this trend, but investment in additional equipment may be
      impractical. OBJECTIVES: To compare CD34(+) cell counting results by using 2
      widely available flow cytometry systems, with and without the use of a separate
      hematology analyzer (ie, single-platform versus dual-platform methodologies).
      DESIGN: Whole blood and peripheral blood stem cell (PBSC) samples were analyzed
      from 13 healthy allogeneic PBSC donors and 46 autologous PBSC donors with various
      malignancies. The Cytomics FC500 (Beckman Coulter, Fullerton, California) was
      compared with the FACSCalibur (BD Biosciences, San Jose, California). Dual
      platform CD34(+) cell counting incorporated data from a KX-21 hematology analyzer
      (Sysmex, Kobe, Japan). RESULTS: Subtle differences in CD34(+) cell counting
      between 2 systems and 2 methods did not achieve statistical significance.
      CONCLUSION: Different systems and methods for CD34(+) cell enumeration, properly
      validated, can support care for patients undergoing transplants and provide
      meaningful data for multicenter studies or meta-analyses.

PMID- 21732783
TI  - Application of thrombolytic drugs on clotted blood and bone marrow specimens to
      generate usable cells for cytogenetic analyses.
AB  - CONTEXT: Clotted blood and bone marrow specimens account for a large proportion
      of failed cytogenetic studies. There are no published protocols describing
      salvage of clotted specimens such that conventional chromosome or fluorescence in
      situ hybridization (FISH) studies can be performed. OBJECTIVE: To evaluate the
      utility of thrombolytic drugs on clotted blood samples to yield intact cells
      suitable for cytogenetic analysis. DESIGN: Five commercially available
      thrombolytic drugs (alteplase, urokinase, streptokinase, tenecteplase, reteplase)
      were evaluated in a series of blinded experiments to identify the best drug for
      lysing clots to produce samples suitable for chromosome and FISH studies. After
      the selection of alteplase as the drug yielding the most promising results, a
      comparative study between alteplase (0.75 mg/ml) and a commercially available
      anticlotting reagent (ACR) was performed. For each sample, mitotic index,
      chromosome length, and quality of slides prepared for conventional chromosome and
      FISH analyses were evaluated. RESULTS: Alteplase-treated samples produced a
      higher mitotic index than those treated with ACR while showing equivalent quality
      in conventional chromosome and FISH studies. We have demonstrated the utility of
      treating clotted blood samples with alteplase before cell culture to yield cells
      suitable for cytogenetic analysis. Since clinical implementation, this technique
      has been applied to more than 250 bone marrow samples, with a 93% success rate.
      CONCLUSIONS: We believe the routine use of alteplase on clotted blood and bone
      marrow specimens should become standard for cytogenetics laboratories and may
      have similar utility in salvaging clotted specimens for other clinical assays
      requiring intact cells for analysis.

PMID- 21732784
TI  - CallWall: tracking resident calls to improve clinical utilization of pathology
      laboratories.
AB  - CONTEXT: Clinical pathology (CP) laboratories are used for millions of tests each
      year. These lead to thousands of calls to CP residents. However, although
      laboratory utilization is a frequent topic of study, clinical utilization--the
      content of the interactions between clinicians and CP residents--is not. Because
      it reflects questions about laboratory utilization, clinical utilization could
      suggest ways to improve both training and care by reducing diagnostic error.
      OBJECTIVES: To build and implement a secure, scalable Web-based system to allow
      CP residents at any hospital to track the calls they receive, the interaction's
      context, and the action taken as a result, with evidence where applicable, and to
      use this system to report on clinical utilization at a major academic hospital.
      DESIGN: Entries were analyzed from a nearly year-long period to describe the
      clinical utilization of CP at a large academic teaching hospital. RESULTS:
      Sixteen residents logged 847 calls during 10 months, roughly evenly distributed
      among transfusion medicine, chemistry, microbiology, and hematopathology. Calls
      covered 94 different analytes in chemistry and 71 different organisms or tests in
      microbiology. Analysis revealed areas where CP can improve clinical care through
      educating the clinical services, for example, about ordering Rh immune globulin,
      testosterone testing, and diagnosis of tick-borne diseases. Documenting calls
      also highlighted patterns among residents. CONCLUSIONS: Clinical utilization is a
      potentially rich knowledge base for improving patient care and resident training.
      Our resident call-tracking system is a useful way for measuring clinical
      utilization and mining it for actionable information.

PMID- 21732786
TI  - Emergence of a high-grade sarcoma in a recurrent meningioma: malignant
      progression or collision tumor?
AB  - Anaplastic meningiomas that resemble sarcomas often reveal clues to their
      meningothelial differentiation or develop in a plausible setting that confirms
      their meningothelial origin. Malignant mesenchymal neoplasms without obvious
      evidence of meningothelial differentiation or origin are more likely to be true
      primary or metastatic sarcomas. Because of their clinical and biological
      differences, it is important to distinguish anaplastic meningioma from a sarcoma.
      We present a 67-year-old woman with multiple meningiomas, who developed a high
      grade spindle cell tumor 6 months after the resection of a World Health
      Organization grade I meningioma. It was not clear whether this tumor represented
      a malignant transformation of meningioma or a primary sarcoma. Malignant
      transformation of a meningioma is exceptional within this short period and a
      coexisting sarcoma and meningioma are equally uncommon. Even though these
      malignant neoplasms are rare in general, they appear to be more prevalent in
      patients with multiple meningiomas including those with neurofibromatosis type 2.

PMID- 21732785
TI  - Mitochondrial disorders of DNA polymerase gamma dysfunction: from anatomic to
      molecular pathology diagnosis.
AB  - CONTEXT: Primary mitochondrial dysfunction is one of the most common causes of
      inherited disorders predominantly involving the neuromuscular system. Advances in
      the molecular study of mitochondrial DNA have changed our vision and our approach
      to primary mitochondrial disorders. Many of the mitochondrial disorders are
      caused by mutations in nuclear genes and are inherited in an autosomal recessive
      pattern. Among the autosomal inherited mitochondrial disorders, those related to
      DNA polymerase gamma dysfunction are the most common and the best studied.
      Understanding the molecular mechanisms and being familiar with the recent
      advances in laboratory diagnosis of this group of mitochondrial disorders are
      essential for pathologists to interpret abnormal histopathology and laboratory
      results and to suggest further studies for a definitive diagnosis. OBJECTIVES: To
      help pathologists better understand the common clinical syndromes originating
      from mutations in DNA polymerase gamma and its associated proteins and use the
      stepwise approach of clinical, laboratory, and pathologic diagnosis of these
      syndromes. DATA SOURCES: Review of pertinent published literature and relevant
      Internet databases. CONCLUSIONS: Mitochondrial disorders are now better
      recognized with the development of molecular tests for clinical diagnosis. A
      cooperative effort among primary physicians, diagnostic pathologists,
      geneticists, and molecular biologists with expertise in mitochondrial disorders
      is required to reach a definitive diagnosis.

PMID- 21732787
TI  - Cutaneous protothecosis.
AB  - Prototheca species are an achlorophyllic algae that cause infections primarily in
      immunocompromised individuals. At least one-half of infectious cases are
      cutaneous. Because protothecosis is seldom suspected clinically, patients may be
      subjected to various treatment modalities for extended periods without
      satisfactory results. Cutaneous protothecosis shares similar clinical and
      pathologic findings with deep tissue fungal mycoses. The typical presentation
      occurs most commonly on the face and extremities as erythematous plaques,
      nodules, or superficial ulcers. Prototheca spp are spherical, unicellular,
      nonbudding organisms that are sometimes noted on routine hematoxylin-eosin
      staining but are best visualized with periodic acid-Schiff and Gomori methenamine
      silver histochemical stains. Although protothecosis can be diagnosed on biopsy,
      culture of the organism on a medium such as Sabouraud dextrose agar is required
      for definitive diagnosis. Treatment may require a combination of surgical
      excision and antifungal agents. Therefore, cutaneous protothecosis should be
      considered in a lesion that appears suspicious for the more-common fungal
      infections.

PMID- 21732788
TI  - Sarcomatoid carcinoma of esophagus.
AB  - Sarcomatoid carcinoma of the esophagus is an uncommon malignancy, representing
      approximately 2% of esophageal carcinomas. It has also been referred to as
      carcinosarcoma, pseudosarcoma, pseudosarcomatous squamous cell carcinoma, spindle
      cell carcinoma, and polypoid carcinoma, reflecting the uncertainty of its
      pathogenesis. Histologically, carcinomatous and sarcomatous components coexist.
      The clinical and radiologic findings resemble other esophageal neoplasms.
      Sarcomatoid carcinoma often presents as a large, intraluminal, polypoid mass on
      barium esophagram. Despite its size, however, sarcomatoid carcinoma has a more
      favorable prognosis than other malignant esophageal neoplasms, likely because of
      its exophytic growth into the lumen, rather than deep invasion. This article
      provides a brief overview of the clinicopathologic features and possible
      pathogenesis of this uncommon tumor.

PMID- 21732791
TI  - Neoplastic transformation in vitro by mixed beams of high-energy iron ions and
      protons.
AB  - The radiation environment in space is complex in terms of both the variety of
      charged particles and their dose rates. Simulation of such an environment for
      experimental studies is technically very difficult. However, with the variety of
      beams available at the National Space Research Laboratory (NSRL) at Brookhaven
      National Laboratory (BNL) it is possible to ask questions about potential
      interactions of these radiations. In this study, the end point examined was
      transformation in vitro from a preneoplastic to a neoplastic phenotype. The
      effects of 1 GeV/n iron ions and 1 GeV/n protons alone provided strong evidence
      for suppression of transformation at doses <=5 cGy. These ions were also studied
      in combination in so-called mixed-beam experiments. The specific protocols were a
      low dose (10 cGy) of protons followed after either 5-15 min (immediate) or 16-24
      h (delayed) by 1 Gy of iron ions and a low dose (10 cGy) of iron ions followed
      after either 5-15 min or 16-24 h by 1 Gy of protons. Within experimental error
      the results indicated an additive interaction under all conditions with no
      evidence of an adaptive response, with the one possible exception of 10 cGy iron
      ions followed immediately by 1 Gy protons. A similar challenge dose protocol was
      also used in single-beam studies to test for adaptive responses induced by 232
      MeV/n protons and (137)Cs gamma radiation and, contrary to expectations, none
      were observed. However, subsequent tests of 10 cGy of (137)Cs gamma radiation
      followed after either 5-15 min or 8 h by 1 Gy of (137)Cs gamma radiation did
      demonstrate an adaptive response at 8 h, pointing out the importance of the
      interval between adapting and challenge dose. Furthermore, the dose-response data
      for each ion alone indicate that the initial adapting dose of 10 cGy used in the
      mixed-beam setting may have been too high to see any potential adaptive response.

PMID- 21732792
TI  - SIVmac251 is inefficiently transmitted to rhesus macaques by penile inoculation
      with a single SIVenv variant found in ramp-up phase plasma.
AB  - Abstract   Despite the fact that approximately half of all HIV patients acquire
      infection through penile exposure, there have been no recent studies of penile
      SIV transmission in rhesus macaques and the nature of the virus variants
      transmitted, target cells, and pathways of virus dissemination to systemic
      lymphoid tissues are not known. Single genome amplification (SGA) and sequencing
      of HIV-1 RNA in plasma of acutely infected humans allows the identification and
      enumeration of transmitted/founder viruses responsible for productive systemic
      infection. Studies using the SGA strategy have shown that intrarectal and
      intravaginal SIV transmission to macaques recapitulates key features of human HIV
      transmission. To date, no studies have used the SGA assay to identify
      transmitted/founder virus(es) in macaques infected after penile SIV exposure.
      Here we report that SIV can be transmitted by penile SIV exposure. However,
      similar exposure to a high-dose inoculum infects only about half the animals,
      which is about 50% less efficient transmission than occurs after vaginal SIV
      challenge. In addition, only a single SIV env variant established the systemic
      infection in all five animals that became infected after penile exposure, a
      result that is consistent with low incidence and few transmitted HIV variants in
      heterosexually infected men. Our results suggest that the penile transmission of
      SIVmac251 in rhesus macaques recapitulates the key features of penile HIV-1
      transmission and may provide insight into host or viral factors that permit
      penile transmission and dissemination. Furthermore, this SIV challenge exposure
      route will be useful in testing vaccines and other prophylactic approaches.

PMID- 21732793
TI  - Molecular characteristics of HIV type 1 infection among prisoners from Central
      Western Brazil.
AB  - Abstract   This study among antiretroviral-experienced prisoners from central
      western Brazil investigated mutations associated with secondary resistance to
      nucleoside/nonnucleoside reverse transcriptase inhibitors (NRTI/NNRTI), protease
      inhibitors (Stanford HIV-1 Resistance/International Aids Society Databases), and
      HIV-1 subtypes (REGA/phylogenetic analyses/SimPlot). Twenty-seven prisoners from
      three prisons (16 males and four females from Mato Grosso do Sul State and seven
      males from Goias State) had HIV-1 protease and reverse transcriptase fragments
      sequenced after nested PCR. Median age was 35 years. Seven males and two females
      were intravenous drug users, three males referred homosexual practice. Resistance
      mutations were present in 37% (10/27): NRTI+NNRTI mutations (n=5), NRTI mutations
      (n=3), multidrug-resistant mutations (n=2). Subtype B (48%), subtype C (11%),
      B/F1, B/C, and F1/B/C recombinants (40.7%) were detected. Possible intraprison
      transmissions were identified: two intravenous drug user females (subtype C); two
      clusters among homosexual males (subtype B and B/F1). High resistance rate and
      possible intraprison transmission highlight the need for improved prevention,
      counseling, and treatment strategies for prisoners.

PMID- 21732794
TI  - Highlights from the July 2011 issue of DNA and Cell Biology.

PMID- 21732795
TI  - Round two in the heavyweight match with diabetes.

PMID- 21732796
TI  - Seeking patient-centered solutions to a national epidemic.

PMID- 21732797
TI  - Comparison of a novel insulin bolus-patch with pen/syringe injection to deliver
      mealtime insulin for efficacy, preference, and quality of life in adults with
      diabetes: a randomized, crossover, multicenter study.
AB  - OBJECTIVE: This study compared the efficacy, safety, device satisfaction, and
      quality of life (QOL) in people with diabetes using an insulin bolus-patch versus
      current devices (pen/syringe) to deliver mealtime insulin. RESEARCH DESIGN AND
      METHODS: Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2)
      were randomized to bolus-patch or current injection device (55% pen and 45%
      syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study.
      Efficacy was assessed by equivalence in mean daily seven-point blood glucose
      (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device
      effects (ADEs), and adverse events (AEs). Device satisfaction was determined by
      the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the
      validated Diabetes Specific QOL Scale (DSQOLS). RESULTS: Using bolus-patch, MDBG
      (mean+/-SE) was equivalent to that using pen/syringe (8.61+/-0.28 vs. 9.02+/-0.26
      mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower
      using bolus-patch (3.18+/-0.18 vs. 3.63+/-0.17 mmol/L; P=0.004), as was the
      coefficient of variation (CV) (37.2+/-1.7 vs. 40.3+/-1.7%; P=0.046). Hemoglobin
      A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between
      groups. There were no severe hypoglycemia episodes or serious ADEs. Between
      device AEs were comparable. Subjects scored better on six of seven subscales on
      the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus
      pen/syringe. At study completion, 76% of subjects would choose to switch to bolus
      patch (P=0.001). CONCLUSIONS: Delivery of mealtime insulin with bolus-patch
      compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven
      point blood glucose measurements, good safety, significant device satisfaction,
      and improved QOL.

PMID- 21732798
TI  - Exenatide once-weekly clinical development: safety and efficacy across a range of
      background therapies.
AB  - In patients with type 2 diabetes mellitus (T2DM), the physiologic glucagon-like
      peptide-1 (GLP-1) response, which is involved in glucose regulation through
      several mechanisms, is dysfunctional. GLP-1 receptor agonists can fill an unmet
      therapeutic need in the treatment of T2DM: improving glycemic control without
      increasing the risk of hypoglycemia (except with concomitant sulfonylureas) and
      reducing weight in a substantial proportion of patients. GLP-1 receptor agonists
      have impacted established disease treatment algorithms for T2DM. For example, in
      2009 the American Diabetes Association and European Association for the Study of
      Diabetes revised their consensus treatment algorithm to incorporate GLP-1
      receptor agonists. GLP-1 receptor agonists were originally represented by
      exenatide BID (ExBID), a short-acting agent requiring twice-daily injections at
      mealtime. The longer-acting agent liraglutide, requiring once-daily injections,
      recently received regulatory approval. Several other long-acting agents are in
      clinical development, one of which is the once-weekly formulation of exenatide
      (exenatide once weekly [ExQW]). This article reviews the clinical development of
      ExQW in the DURATION program. Patients in theses clinical trials were receiving
      various background treatments, ranging from lifestyle therapy to combination oral
      therapy, although the majority (68%) received metformin monotherapy.
      Specifically, safety, glycemic control, and weight were compared in patients
      treated with ExQW versus ExBID, sitagliptin, pioglitazone, or insulin glargine.
      Moreover, measures of beta-cell function, cardiovascular risk, inflammation, and
      hepatic health were investigated. During ExQW clinical development, consistent
      clinical efficacy (glycosylated hemoglobin, -1.5% to -1.9%; weight, -2 kg to -4
      kg) and safety data were observed in patients with T2DM treated with ExQW.

PMID- 21732800
TI  - Kinematics and energy expenditure of sitting t'ai chi.

PMID- 21732801
TI  - Evolution of inequalities in breast and cervical cancer screening in Barcelona:
      population surveys 1992, 2001, and 2006.
AB  - OBJECTIVE: To describe and compare breast and cervical cancer screening among
      women in Barcelona in 1992, 2001, and 2006 by social class, age, and screening
      approach. METHODS: This was a study of trends based on analysis of Barcelona
      health interview surveys for the years 1992 (n=5,003), 2001 (n=10,030), and 2006
      (n=6,050). Dependent variables were having regular mammographies (at least every
      2 years) and having regular cytologic testing (at least every 3 years).
      Independent variables were age, social class, and survey year. A descriptive
      analysis was carried out. To compare prevalence in terms of social class and the
      years studied, we calculated prevalence differences (PD) and prevalence ratios
      (PR) by fitting robust Poisson regression models. RESULTS: In 1992, women aged
      40?49 had more regular mammographies than those aged 50?69, with social class
      inequalities in both age groups. Having cervical cancer screening was more common
      than having breast cancer screening, with prevalence varying from 46.4% in the
      low social classes to 59.2% in the high classes. In 2001, breast cancer screening
      had risen, particularly in women aged 50?69, a tendency that had stabilized by
      2006. Inequalities diminished over the period, more markedly in women aged 50?69;
      PRs of 1.22 and 1.58, respectively, for high and middle social classes with
      respect to the lowest class in 1992 fell to PRs of 1.07 and 1.08, respectively,
      in 2006. In the case of cervical cancer screening, inequalities also diminished
      but not to the same extent. CONCLUSIONS: Preventive screening for breast and
      cervical cancer has increased, and the population screening program for breast
      cancer among women aged 50?69 years appears to contribute more than opportunistic
      screening for cervical cancer in reducing social class inequalities.

PMID- 21732802
TI  - Improvement in posttraumatic stress disorder in postconflict Rwandan women.
AB  - BACKGROUND: Depression and posttraumatic stress disorder (PTSD) are common in
      developing and postconflict countries. The purpose of this study is to examine
      longitudinal changes in PTSD in HIV-infected and uninfected Rwandan women who
      experienced the 1994 genocide. METHODS: Five hundred thirty-five HIV-positive and
      163 HIV-negative Rwandan women in an observational cohort study were followed for
      18 months. Data on PTSD symptoms were collected longitudinally by the Harvard
      Trauma Questionnaire (HTQ) and analyzed in relationship to demographics, HIV
      status, antiretroviral treatment (ART), and depression. PTSD was defined as a
      score on the HTQ of >=2. RESULTS: There was a continuing reduction in HTQ scores
      at each follow-up visit. The prevalence of PTSD symptoms changed significantly,
      with 61% of the cohort having PTSD at baseline vs. 24% after 18 months. Women
      with higher HTQ score were most likely to have improvement in PTSD symptoms
      (p<0.0001). Higher rate of baseline depressive symptoms (p<0.0001) was associated
      with less improvement in PTSD symptoms. HIV infection and ART were not found to
      be consistently related to PTSD improvement. CONCLUSIONS: HIV care settings can
      become an important venue for the identification and treatment of psychiatric
      problems affecting women with HIV in postconflict and developing countries.
      Providing opportunities for women with PTSD symptoms to share their history of
      trauma to trained counselors and addressing depression, poverty, and ongoing
      violence may contribute to reducing symptoms.

PMID- 21732803
TI  - Longitudinal changes in feeding among children with cerebral palsy between the
      ages of 4 and 7 years.
AB  - OBJECTIVE: To examine differences in feeding among children with cerebral palsy
      (CP) who varied in the severity of their oral motor involvement; to examine
      longitudinal change in feeding behaviours for different severity groups. METHOD:
      Twenty-three children with CP participated (mean age = 4.53 years at the first
      time point). Feeding data were collected from parent questionnaires at 6 month
      intervals over 30 months. RESULTS: Significant differences were observed among
      severity groups for all feeding variables except coughing and choking during
      meals. Only one variable, coughing, showed significant change over time.
      CONCLUSIONS: Children with CP who had severe oral-motor involvement had marked
      and pervasive feeding difficulties which showed some fluctuation with time, but
      generally were stable. Children with CP who did not have oral motor involvement
      and those who had mild-moderate involvement also showed little-to-no change over
      time and had fewer problems than those in the severe group.

PMID- 21732804
TI  - Multidisciplinary perspective for cerebral palsy assessment after an
      international, classification of functioning, disability and health training.
AB  - OBJECTIVE: To assess knowledge related to the ICF before and after an ICF
      training and to identify items to compose a monocentric rehabilitation ICF code
      set for cerebral palsy (CP). METHODS: (a) DESIGN: A cross-sectional study with a
      descriptive-explorative design. (b) PARTICIPANTS: Professionals from the fields
      of physiotherapy, nutrition, dentistry, occupational therapy, psychology, social
      work, speech therapy and medicine. (c) INSTRUMENT: A questionnaire to assess
      ICF's knowledge (total score = 17). RESULTS: A high effect size of the ICF
      training was found (Cohen's d = 4.10). Ninety-one and 43 ICF categories were
      selected for a comprehensive evaluation and triage, respectively, for CP.
      CONCLUSION: ICF categories were identified to compose a comprehensive evaluation
      and for triage through an ICF code sets for CP. Studies are needed to validate
      the instrument on the knowledge of the ICF and to test the impact of ICF's
      training for clinical rehabilitation of CP.

PMID- 21732805
TI  - The relationship between race and challenging behaviours in infants and toddlers
      with autistic disorder and pervasive developmental disorder-not otherwise
      specified.
AB  - OBJECTIVE: To examine the contributions of race and diagnostic category to
      endorsement rates of challenging behaviours in infants and toddlers with autism,
      PDD-NOS and atypical development without ASD, using the Baby and Infant Screen
      for Children with aUtIsm Traits, Part-3 (BISCUIT Part-3). DESIGN: Multivariate
      analyses of variance (MANOVAs) on each sub-scale of the BISCUIT Part-3. Follow-up
      univariate analyses and post-hoc tests as needed. METHODS: Scores on the BISCUIT
      Part-3 were compared for 453 Caucasian and 409 African-American infants and
      toddlers, grouped by race and diagnosis. RESULTS: Significant differences between
      races were found on five out of 10 aggressive behaviours, while no significant
      differences were found on self-injurious or stereotypic behaviours. Significant
      differences between diagnostic groups were found on all behaviours. CONCLUSION:
      Cultural factors should be taken into account when examining challenging
      behaviours in infants and toddlers with ASD.

PMID- 21732806
TI  - The occurrence of challenging behaviours in children with autism spectrum
      disorders and atypical development.
AB  - OBJECTIVE: This study examines the occurrence of challenging behaviours in
      children with ASDs and atypical development. DESIGN: This study is a descriptive
      non-experimental design that inspects the frequencies of challenging behaviours
      among two diagnostic groups. This type of methodology is important since research
      in this area is still in the beginning stages of development. METHODS: The sample
      consisted of 2131 children, with 633 having an ASD and 1498 having atypical
      development. The Baby and Infant Screen for Children with aUtIsm Traits-Part 3
      (BISCUIT-Part 3) assesses problematic behaviours within this population. The
      frequencies of challenging behaviours were examined along with an inspection of
      the co-occurring items. RESULTS: Greater percentages of problematic behaviours
      were found in the ASD group as compared to the group with atypical development.
      CONCLUSION: Challenging behaviours are variables affecting the behavioural
      presentation of those with ASDs and may be considered into the treatment plans
      for these children.

PMID- 21732807
TI  - Group swimming and aquatic exercise programme for children with autism spectrum
      disorders: a pilot study.
AB  - OBJECTIVE: To evaluate the effectiveness of a 14-week aquatic exercise programme
      for children with autism spectrum disorders (ASD). DESIGN: Non-randomized control
      trial. METHODS: Twelve children participated in this pilot study with seven
      participants in the aquatic exercise group and five in the control group. The
      programme was held twice per week for 40 minutes per session. Swimming skills,
      cardiorespiratory endurance, muscular endurance, mobility skills and participant
      and parent satisfaction were measured before and after the intervention. RESULTS:
      No significant between-group changes were found. Within-group improvements for
      swimming skills were found for the intervention group. Programme attendance was
      high. Parents and children were very satisfied with the programme activities and
      instructors. CONCLUSIONS: This pilot programme was feasible and showed potential
      for improving swimming ability in children with ASD. Exercise intensity was low
      for some participants, most likely contributing to a lack of significant findings
      on fitness outcomes.

PMID- 21732808
TI  - A man with severe Alzheimer's disease stops wandering during a picture colouring
      activity.
AB  - OBJECTIVE: To assess the effects of a picture colouring activity on the wandering
      (and constructive engagement) of a man with severe Alzheimer's disease. METHOD:
      The colouring activity was compared with a music listening condition and a
      baseline/control condition. A choice phase involving the colouring activity and
      the music condition was also implemented. RESULTS: Wandering was constant during
      the baseline condition, but it was reduced to low or virtually 0% levels during
      the music condition and picture colouring activity. Moreover, the patient
      regularly selected the colouring activity (which also promoted constructive
      engagement) during the choice phase. CONCLUSION: Simple leisure activities, such
      as picture colouring, might help patients with Alzheimer's disease reduce
      wandering.

PMID- 21732809
TI  - Going beyond the identification of change facilitators to effectively implement a
      new model of services: lessons learned from a case example in paediatric
      rehabilitation.
AB  - PURPOSE: To identify facilitators and barriers to service reorganization, how
      they evolved and interacted to influence change during the implementation of a
      new service delivery model of paediatric rehabilitation. METHODS: Over 3 years,
      different stakeholders responded to SWOT questionnaires (n = 139) and
      participated in focus groups (n = 19) and telephone interviews (n = 13). A
      framework based on socio constructivist theories made sense of the data. RESULTS:
      Facilitators related to the programme's structure (e.g. funding), the actors
      (e.g. willingness to test the new service model) and the change management
      process (e.g. participative approach). Some initial facilitators became barriers
      (e.g. leadership lacked at the end), while other barriers emerged (e.g. lack of
      tools). Understanding factor interactions requires examining the multiple actors'
      intentions, actions and consequences and their relations with structural
      elements. CONCLUSIONS: Analysing facilitators and barriers helped better
      understand the change processes, but this must be followed by concrete actions to
      successfully implement new paediatric rehabilitation models.

PMID- 21732810
TI  - Factors associated with self-reported mammography use for women with and women
      without a disability.
AB  - BACKGROUND: Although their risk of breast cancer is similar to that of women
      without a disability, women with a disability might be less likely to obtain a
      mammogram within the recommended time frame. The purpose of this study was to
      expand our knowledge of the association between mammography use and having a
      disability by controlling for sociodemographic and health variables. METHODS:
      Data from the 2008 Behavioral Risk Factor Surveillance System (BRFSS) were used
      to obtain prevalence of self-reported mammography use in the past 2 years among
      U.S. women >=40 years of age (n=204,981) as well as women 50-74 years of age
      (n=122,374). Logistic regression was used to estimate associations between
      disability and obtaining a mammogram for each age cohort, controlling for
      sociodemographic factors. RESULTS: Prevalence of self-reported mammography use is
      lower for women with a disability (72.2% for women >=40 years of age and 78.1%
      for women 50-74 years of age) than women without a disability (77.8% and 82.6%,
      respectively). Women with a disability had lower odds of mammography use than
      women without a disability for both age cohorts (>=40, adjusted odds ratio [aOR]
      0.92, p=0.01; 50-74 years, aOR 0.92, p=0.03). CONCLUSIONS: Disparities in
      obtaining a mammogram at recommended screening intervals persist for women with
      disabilities. This demonstrates the need for continued health promotion and
      prevention activities directed toward women with a disability to improve their
      accessibility to obtaining a mammogram.

PMID- 21732811
TI  - Vitamin D status and Framingham risk score in overweight postmenopausal women.
AB  - BACKGROUND: Epidemiologic studies have suggested associations between vitamin D
      status and coronary heart disease (CHD) risk. The purpose of this work was to
      determine if vitamin D status was predictive of CHD risk assessed by Framingham
      risk score (FRS) in overweight, Caucasian, postmenopausal women, using the
      baseline data collected in a clinical trial. METHODS: The study comprised 178
      women aged 42-67 years (mean+/-standard deviation [SD] 55.7+/-4.3). Fasting serum
      was used to analyze blood lipids and vitamin D. The status of the latter was
      determined based on serum 25-hydroxyvitamin D [25(OH)D], with inadequacy defined
      as serum 25(OH)D <75 nmol/L (or <50.0 nmol/L, per new Institute of Medicine
      recommendations). Usual dietary intake and activity were assessed using 3-day
      food and 2-day activity records, respectively. Education, medical history, blood
      pressure, and anthropometric measures were obtained as well. Season was
      determined based on date of blood draw. RESULTS: Mean serum 25(OH)D concentration
      was 65.3+/-27.5 nmol/L (range 7.0-147.6 nmol/L); 66% (n=118) and 32% (n=57) of
      subjects were vitamin D insufficient [25(OH)D <75 nmol/L or <50 nmol/L,
      respectively] of which 14% (n=25) were vitamin D deficient [25(OH)D <37.5
      nmol/L]. Body mass index (BMI) was a significant negative and dietary vitamin D
      positive predictor of 25(OH)D. In hierarchical regression, FRS was predicted by
      education level only. No association was observed between 25(OH)D and FRS
      (p=0.981). CONCLUSIONS: Serum 25(OH)D concentrations were inversely associated
      with BMI, but no relationship with FRS was found. Given the physiologic
      importance of vitamin D, further investigations aimed at determining the effects
      of obesity and heart disease on vitamin D requirements are warranted.

PMID- 21732812
TI  - Aneuploidy rates in failed pregnancies following assisted reproductive
      technology.
AB  - BACKGROUND: Approximately 10%-15% of clinically recognized pregnancies end with a
      first trimester loss. Cytogenetic analysis of products of conception (POC) has
      revealed that a large proportion of these spontaneous miscarriages are a result
      of chromosomal abnormalities. However, relatively few studies have evaluated
      chromosomal abnormalities in pregnancies achieved using assisted reproductive
      technologies (ART). Here, we review the incidence and type of chromosomal
      abnormalities that occurred in our infertility patient population undergoing ART
      and provide a review of the literature pertaining to this subject. METHODS: A
      retrospective chart review of all patients from our medical center who conceived
      using ART between January 2000 and January 2008, who experienced a subsequent
      early pregnancy loss, and whose POCs were successfully karyotyped were included.
      We also conducted a literature review in PubMed, searching for other articles on
      this subject. RESULTS: Two hundred fourteen patients conceived with ART,
      experienced an early loss, and subsequently underwent a dilation and curettage
      (D&C) between 2000 and 2008. A total of 59 (27%) patients chose to have
      cytogenetic testing, and their POCs were successfully karyotyped. The overall
      rate of aneuploidy in this group was 83%. Our PubMed search revealed a total of
      12 studies that were identified and evaluated and deemed appropriate for review.
      CONCLUSIONS: Consistent with most of the literature, we found a high rate of
      aneuploidy present in infertile patients conceiving using ART. Because an
      abnormal karyotype provides an explanation for an early loss, this and other
      studies seem to suggest that routinely carrying out this assessment in such
      patients may be of value.

PMID- 21732813
TI  - MicroRNA and messenger RNA analyses of mesenchymal stem cells derived from teeth
      and the Wharton jelly of umbilical cord.
AB  - Microarray analyses of transcriptomes have been used to characterize mesenchymal
      stem cells (MSCs) of various origins. MicroRNAs (miRNAs) are short, nonprotein
      coding RNAs involved in post-transcriptional gene inhibition in a variety of
      tissues, including cancer cells and MSCs. This study has integrated the use of
      miRNA and mRNA expression profiles to analyze human MSCs derived from Wharton's
      jelly (WJ) of the umbilical cord, milk teeth (MT), and adult wisdom teeth (AT).
      Because both miRNA and mRNA expression in MT and AT MSCs were so similar, they
      were combined together as tooth MSCs for comparison with WJ MSCs. Twenty-five
      genes that were up-regulated in tooth MSCs and 41 genes that were up-regulated in
      WJ MSCs were identified by cross-correlating miRNA and mRNA profiles. Functional
      network analysis show that tooth MSCs signature genes, represented by SATB2 and
      TNFRSF11B, are involved in ossification, bone development, and actin cytoskeleton
      organization. In addition, 2 upregulated genes of tooth MSCs-NEDD4 and EMP1-have
      been shown to be involved in neuroectodermal differentiation. The signature genes
      of WJ MSCs, represented by KAL1 and PAPPA, are involved in tissue development,
      regulation of cell differentiation, and bone morphogenetic protein signaling
      pathways. In conclusion, the combined interrogation of miRNA and mRNA expression
      profiles in this study proved useful in extracting reliable results from a genome
      wide comparison of multiple types of MSCs. Subsequent functional network analysis
      provided further functional insights about these MSCs.

PMID- 21732814
TI  - Isolation and characterization of human anterior cruciate ligament-derived
      vascular stem cells.
AB  - The anterior cruciate ligament (ACL) usually fails to heal after rupture mainly
      due to the inability of the cells within the ACL tissue to establish an adequate
      healing process, making graft reconstruction surgery a necessity. However, some
      reports have shown that there is a healing potential of ACL with primary suture
      repair. Although some reports showed the existence of mesenchymal stem cell-like
      cells in human ACL tissues, their origin still remains unclear. Recently, blood
      vessels have been reported to represent a rich supply of stem/progenitor cells
      with a characteristic expression of CD34 and CD146. In this study, we attempted
      to validate the hypothesis that CD34- and CD146-expressing vascular cells exist
      in hACL tissues, have a potential for multi-lineage differentiation, and are
      recruited to the rupture site to participate in the intrinsic healing of injured
      ACL. Immunohistochemistry and flow cytometry analysis of hACL tissues
      demonstrated that it contains significantly more CD34 and CD146-positive cells in
      the ACL ruptured site compared with the noninjured midsubstance. CD34+CD45- cells
      isolated from ACL ruptured site showed higher expansionary potentials than
      CD146+CD45- and CD34-CD146-CD45- cells, and displayed higher differentiation
      potentials into osteogenic, adipogenic, and angiogenic lineages than the other
      cell populations. Immunohistochemistry of fetal and adult hACL tissues
      demonstrated a higher number of CD34 and CD146-positive cells in the ACL septum
      region compared with the midsubstance. In conclusion, our findings suggest that
      the ACL septum region contains a population of vascular-derived stem cells that
      may contribute to ligament regeneration and repair at the site of rupture.

PMID- 21732815
TI  - Efficient hematopoietic redifferentiation of induced pluripotent stem cells
      derived from primitive murine bone marrow cells.
AB  - Heterogeneity among induced pluripotent stem cell (iPSC) lines with regard to
      their gene expression profile and differentiation potential has been described
      and at least partly linked to the tissue of origin. Here, we generated iPSCs from
      primitive [lineage negative (Lin(neg))] and nonadherent differentiated [lineage
      positive (Lin(pos))] bone marrow cells (BM-iPSC), and compared their
      differentiation potential to that of fibroblast-derived iPSCs (Fib-iPSC) and
      embryonic stem cells (ESC). In the undifferentiated state, individual iPSC clones
      but also ESCs proved remarkably similar when analyzed for alkaline phosphatase
      and SSEA-1 staining, endogenous expression of the pluripotency genes Nanog, Oct4,
      and Sox2, or global gene expression profiles. However, substantial differences
      between iPSC clones were observed after induction of differentiation, which
      became most obvious upon cytokine-mediated instruction toward the hematopoietic
      lineage. All 3 BM-iPSC lines derived from undifferentiated Lin(neg) cells yielded
      high proportions of cells expressing the hematopoietic differentiation marker
      CD41 and in 2 of these lines high proportions of CD41+/ CD45+ cells were
      detected. In contrast, little hematopoiesis-specific surface marker expression
      was detected in 4 Lin(pos) BM-iPSC and 3 Fib-iPSC lines. These results were
      corroborated by functional studies demonstrating robust colony outgrowth from
      hematopoietic progenitors in 2 of the Lin(neg) BM-iPSCs only. Thus, in
      conclusion, our data demonstrate efficient generation of iPSCs from primitive
      hematopoietic tissue as well as efficient hematopoietic redifferentiation for
      Lin(neg) BM-iPSC lines, thereby supporting the notion of an epigenetic memory in
      iPSCs.

PMID- 21732816
TI  - Neurogenic properties and a clinical relevance of multipotent stem cells derived
      from cord blood samples stored in the biobanks.
AB  - Several innovative therapies with human umbilical cord blood stem cells (SCs) are
      currently developing to treat central nervous system (CNS) diseases. It has been
      shown that cord blood contains multipotent lineage-negative (LinNEG) SCs capable
      of neuronal differentiation. Clinically useful cord blood samples are stored in
      different biobanks worldwide, but the content and neurogenic properties of LinNEG
      cells are unknown. Here we have compared 5 major methods of blood processing:
      Sepax, Hetastarch, plasma depletion, Prepacyte-SC, and density gradient. We
      showed that Sepax-processed blood units contained 10-fold higher number of LinNEG
      cells after cryopreservation in comparison to all other methods. We showed in
      this study that multipotent SCs derived from fresh and frozen cord blood samples
      could be efficiently induced in defined serum-free medium toward neuronal
      progenitors (NF200+, Ki67+). During neuronal differentiation, the multipotent SCs
      underwent precise sequential changes at the molecular and cellular levels: Oct4
      and Sox2 downregulation and Ngn1, NeuN, and PSD95 upregulation, similar to
      neurogenesis process in vivo. We expect that data presented here will be valuable
      for clinicians, researchers, biobanks, and patients and will contribute for
      better efficacy of future clinical trials in regeneration of CNS.

PMID- 21732817
TI  - Mesenchymal stromal cell migration: possibilities to improve cellular therapy.
AB  - Mesenchymal stromal cells (MSC) represent a type of multipotent cells that can be
      isolated from several human tissues and that can be expanded ex vivo for clinical
      application. The regenerative and immune modulatory capacities of MSC have raised
      hopes for clinical applications of MSC. At the moment, many clinical trials
      applying MSC for treatment of multiple diseases are being set up. Currently,
      extensive expansion (3-6 weeks) is required to obtain enough cells for
      transplantation. However, culture-expanded MSC have almost completely lost their
      engraftment potential. MSC expansion cultures are initiated with a heterogeneous,
      poorly defined cell population. It is unknown which MSC populations are expanded
      and how this affects homing capacity. Thus, understanding MSC migration will
      offer perspectives to modulate the expansion protocols to obtain cells that
      maintain migration and homing capacities. This review highlights our current
      understanding of MSC migration with particular emphasis on the possibilities to
      improve MSC-based therapy.

PMID- 21732818
TI  - Expression of Sonic hedgehog during cell proliferation in the human cerebellum.
AB  - The regulation of cell proliferation in the external granular layer (EGL) of the
      developing cerebellum is important for its normal patterning. An important signal
      that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by
      the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors
      of the EGL. Deregulation of Shh signaling has been associated with abnormal
      development, and been implicated in medulloblastomas, which are tumors that arise
      from the cerebellum. Given the importance of the Shh pathway in cerebellum
      development and disease, there has been no systematic study of its expression
      pattern during human cerebellum development. In this study, we describe the
      expression pattern of Shh, its receptor patched, smoothened, and its effectors
      that belong to the Gli family of transcription factors, during normal human
      cerebellum development from 10 weeks of gestational age, and in medulloblastomas
      that represents a case of abnormal cell proliferation in the cerebellum. This
      expression pattern is compared to equivalent stages in the normal development of
      cerebellum in mouse, as well as in tumors. Important differences between human
      and mouse that reflect differences in the normal developmental program between
      the 2 species are observed. First, in humans there appears to be a stage of Shh
      signaling within the EGL, when the PC are not yet the source of Shh. Second,
      unlike in the postnatal mouse cerebellum, expression of Shh in the PC in the
      postnatal human cerebellum is downregulated. Finally, medulloblastomas in the
      human but not in patched heterozygote mouse express Shh. These results highlight
      cross-species differences in the regulation of the Shh signaling pathway.

PMID- 21732819
TI  - Vaccinomics and a new paradigm for the development of preventive vaccines against
      viral infections.
AB  - In this article we define vaccinomics as the integration of immunogenetics and
      immunogenomics with systems biology and immune profiling. Vaccinomics is based on
      the use of cutting edge, high-dimensional (so called "omics") assays and novel
      bioinformatics approaches to the development of next-generation vaccines and the
      expansion of our capabilities in individualized medicine. Vaccinomics will allow
      us to move beyond the empiric "isolate, inactivate, and inject" approach
      characterizing past vaccine development efforts, and toward a more detailed
      molecular and systemic understanding of the carefully choreographed series of
      biological processes involved in developing viral vaccine-induced "immunity."
      This enhanced understanding will then be applied to overcome the obstacles to the
      creation of effective vaccines to protect against pathogens, particularly
      hypervariable viruses, with the greatest current impact on public health. Here we
      provide an overview of how vaccinomics will inform vaccine science, the
      development of new vaccines and/or clinically relevant biomarkers or surrogates
      of protection, vaccine response heterogeneity, and our understanding of
      immunosenescence.

PMID- 21732820
TI  - Publics and vaccinomics: beyond public understanding of science.
AB  - Vaccines have been among the most effective tools for addressing global public
      health challenges. With the advent of genomics, novel approaches for vaccine
      discovery are opening up new opportunities for vaccine development and
      applications, particularly with the expectation of personalized vaccines and the
      possibility of addressing a broader range of infectious diseases. In this
      context, it is useful to reflect on the social contexts of vaccine development as
      these have been influenced by social, ethical, political challenges. This article
      discusses the historical context of vaccine controversies and factors that help
      explain public acceptance and resistance, illustrating that these challenges go
      well beyond simple public misunderstandings. The broader vaccine challenges
      evident along the innovation trajectory, from development to commercialization
      and implementation include problems in research and development, organizational
      issues, and legal and regulatory challenges that may collectively contribute to
      public resistance or confidence. The recent history of genomics provides further
      lessons that the developing field of vaccinomics can learn from.

PMID- 21732822
TI  - Twenty-first century vaccinomics innovation systems: capacity building in the
      global South and the role of Product Development Partnerships (PDPs).
AB  - The availability of sequence information from publicly available complete genomes
      and data intensive sciences, together with next-generation sequencing
      technologies offer substantial promise for innovation in vaccinology and global
      public health in the beginning of the 21st century. This article presents an
      innovation analysis for the nascent field of vaccinomics by describing one of the
      major challenges in this endeavor: the need for capacities in "vaccinomics
      innovation systems" to support the developing countries involved in the creation
      and testing of new vaccines. In particular, we discuss the need for understanding
      how institutional frameworks can enhance capacities as intrinsic to a systems
      approach to health technology development. We focus our attention on the global
      South, meaning the technically less advanced and developing nations in Africa,
      Asia, and Latin America. This focus is timely and appropriate because the
      challenge for innovation in postgenomics medicine is markedly much greater in
      these regions where basic infrastructures are often underresourced and new or the
      anticipated institutional relationships can be fragile. Importantly, we examine
      the role of Product Development Partnerships (PDPs) as a 21st century
      organizational innovation that contributes to strengthening fragile institutions
      and capacity building. For vaccinomics innovation systems to stand the test of
      time in a context of global public health, local communities, knowledge, and
      cultures need to be collectively taken into account at all stages in programs for
      vaccinomics-guided vaccine development and delivery in the global South where the
      public health needs for rational vaccine development are urgent.

PMID- 21732821
TI  - Therapeutic cancer vaccines and translating vaccinomics science to the global
      health clinic: emerging applications toward proof of concept.
AB  - As vaccines evolve to be a more common treatment for some cancers, further
      research is needed to improve the process of developing vaccines and assessing
      response to treatment. Vaccinomics involves a wide-ranging integration of
      multiple high throughput technologies including transcriptional, translational,
      and posttranslational population-based assessments of the human genome,
      transcriptome, proteome, and immunome. Vaccinomics combines the fields of
      immunogenetics, immunogenomics, immunoproteomics, and basic immunology to create
      vaccines that are tailor made to an individual or groups of individuals. This
      broad range of omics applications to tumor immunology includes antigen discovery,
      diagnostic biomarkers, cancer vaccine development, predictors of immune response,
      and clinical response biomarkers. These technologies have aided in the
      advancement of cancer vaccine development, as illustrated in examples including
      NY-ESO-1 originally defined by SEREX, and HER2/neu peptides analyzed via high
      throughput epitope prediction methods. As technology improves, it presents an
      opportunity to improve cancer immunotherapy on a global scale, and attention must
      also be given to utilize these high-throughput methods for the understanding of
      cancer and immune signatures across populations.

PMID- 21732823
TI  - Complementary and alternative medicine practitioners and Accountable Care
      Organizations: the train is leaving the station.
AB  - Legislation that supports the establishment of Accountable Care Organizations
      (ACOs) was recently enacted into law as part of the Patient Protection and
      Affordable Care Act, and in 2012 the Centers for Medicare and Medicaid Services
      will begin contracting with ACOs. Although ACOs will play a significant role in
      reform of the U.S. health care delivery system, thus far, discussions have
      focused exclusively on the coordination of conventional health services. This
      article discusses the potential engagement of the complementary and alternative
      (CAM) workforce in ACOs and the foreseeable impacts of ACO legislation on the
      future of U.S. CAM services.

PMID- 21732824
TI  - Women's use of complementary and alternative medicine for fertility enhancement:
      a review of the literature.
AB  - OBJECTIVES: The use of complementary and alternative medicine (CAM) has increased
      in Western countries, with women identified as the primary users. Women's use of
      CAM in reproductive health is well documented; however, little is known about the
      use of CAM to enhance fertility, despite anecdotal evidence that this is a
      growing trend in reproductive medicine. The objective of this review was to
      examine the literature on women's use of CAM to enhance fertility, focusing on
      prevalence, motivations for use, and how information is sourced. DESIGN: A
      systematic search of multiple databases was conducted using key words and
      selection criteria. RESULTS: A total of eight articles that met the selection
      criteria, published between 1990 and 2010, were found and included in the review.
      The articles were analyzed under five key themes: "user prevalence," "user
      profile," "motivation for use," "expectations and satisfaction," and "referral
      and information sources." This review demonstrates important gaps in the evidence
      regarding women's use of CAM for fertility enhancement. There are no population
      based studies with representative samples, no commonly accepted definitions of
      CAM research, and few studies describing women's motivations for and experiences
      of using CAM for fertility enhancement. Importantly, little is known about
      women's sources of information about CAM in this context. CONCLUSIONS: Nationally
      representative, population-based studies are required to fill the gaps in the
      evidence, provide prevalence rates, and inform policy and clinical practice.

PMID- 21732825
TI  - Effect of Chinese herbal fomentation on arteriovenous fistula maturation.
AB  - OBJECTIVES: The study objectives were to examine the effects of Chinese herbal
      fomentation on radiocephalic arteriovenous fistula (AVF) maturation. METHODS: All
      patients' preoperative evaluation, operative procedure, and follow-up information
      records were reviewed to identify patients undergoing radiocephalic AVF
      procedures for maintenance hemodialysis. All patients underwent preoperative
      vessel ultrasound. The ultrasound examinations were repeated every 2 months after
      the operative procedure. From the day after the operation, the forearm of the
      patient is fomented with a mixture of Dan Shen and Hong Hua in dry powdered form
      dissolved in fresh warm water. The fomentation lasted for 60 minutes, once a day
      for 28 consecutive days. RESULTS: Sixty-four (64) specific access site operations
      were yielded in 62 patients for analysis. Forty-nine (49; 76.6%) of the 64
      fistulas were considered sonographically mature and 15 (23.4%) were deemed
      sonographically immature. The sonographically mature fistulas (n=46) that were
      suitable for puncture had blood flow of 655+/-132 mL/minute, and venous diameter
      of 4.5+/-0.3 mm. The most frequent complication was thrombosis before first use,
      which accounted for 6 AVFs failures to mature (0.16 per patient-year). There were
      two hospitalizations for fistula-related bacteremia in the group (0.05 per
      patient-year). CONCLUSIONS: The Chinese herbal fomentation reduced the frequency
      of early thrombosis of new AVFs and was accompanied by an increase in the
      proportion of AVFs that were suitable for dialysis.

PMID- 21732826
TI  - Letter written in response to van bon et Al.: "Insulin glulisine compared to
      insulin aspart and to insulin lispro administered by continuous subcutaneous
      insulin infusion in patients with type 1 diabetes: a randomized controlled
      trial".

PMID- 21732828
TI  - The Clean Air Act and health--a clearer view from 2011.

PMID- 21732829
TI  - Wnt signaling and Dupuytren's disease.
AB  - BACKGROUND: Dupuytren's disease is a benign fibromatosis of the hands and fingers
      that leads to flexion contractures. We hypothesized that multiple genetic and
      environmental factors influence susceptibility to this disease and sought to
      identify susceptibility genes to better understand its pathogenesis. METHODS: We
      conducted a genomewide association study of 960 Dutch persons with Dupuytren's
      disease and 3117 controls (the discovery set) to test for association between the
      disease and genetic markers. We tested the 35 single-nucleotide polymorphisms
      (SNPs) most strongly associated with Dupuytren's disease (P<1*10(-4)) in the
      discovery set in three additional, independent case series comprising a total of
      1365 affected persons and 8445 controls from Germany, the United Kingdom, and The
      Netherlands. RESULTS: Initially, we observed a significant genomewide association
      between Dupuytren's disease and 8 SNPs at three loci. Tests of replication and
      joint analysis of all data from 2325 patients with Dupuytren's disease and 11,562
      controls yielded an association with 11 SNPs from nine different loci (P<5.0*10(
      8)). Six of these loci contain genes known to be involved in the Wnt-signaling
      pathway: WNT4 (rs7524102) (P=2.8*10(-9); odds ratio, 1.28), SFRP4 (rs16879765)
      (P=5.6*10(-39); odds ratio, 1.98), WNT2 (rs4730775) (P=3.0*10(-8); odds ratio,
      0.83), RSPO2 (rs611744) (P=7.9*10(-15); odds ratio, 0.75), SULF1 (rs2912522)
      (P=2.0*10(-13); odds ratio, 0.72), and WNT7B (rs6519955) (P=3.2*10(-33); odds
      ratio, 1.54). CONCLUSIONS: This study implicates nine different loci involved in
      genetic susceptibility to Dupuytren's disease. The fact that six of these nine
      loci harbor genes encoding proteins in the Wnt-signaling pathway suggests that
      aberrations in this pathway are key to the process of fibromatosis in Dupuytren's
      disease.

PMID- 21732830
TI  - Images in clinical medicine. Nonobstructive hydronephrosis with secondary
      polycythemia.

PMID- 21732831
TI  - Lessons from the trenches--a high-functioning primary care clinic.

PMID- 21732832
TI  - Level IV evidence--adverse anecdote and clinical practice.

PMID- 21732833
TI  - New regimens to prevent tuberculosis in adults with HIV infection.
AB  - BACKGROUND: Treatment of latent tuberculosis in patients infected with the human
      immunodeficiency virus (HIV) is efficacious, but few patients around the world
      receive such treatment. We evaluated three new regimens for latent tuberculosis
      that may be more potent and durable than standard isoniazid treatment. METHODS:
      We randomly assigned South African adults with HIV infection and a positive
      tuberculin skin test who were not taking antiretroviral therapy to receive
      rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600
      mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily
      for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6
      months (control group). The primary end point was tuberculosis-free survival.
      RESULTS: The 1148 patients had a median age of 30 years and a median CD4 cell
      count of 484 per cubic millimeter. Incidence rates of active tuberculosis or
      death were 3.1 per 100 person-years in the rifapentine-isoniazid group, 2.9 per
      100 person-years in the rifampin-isoniazid group, and 2.7 per 100 person-years in
      the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the
      control group (P>0.05 for all comparisons). Serious adverse reactions were more
      common in the continuous-isoniazid group (18.4 per 100 person-years) than in the
      other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of
      Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance.
      CONCLUSIONS: On the basis of the expected rates of tuberculosis in this
      population of HIV-infected adults, all secondary prophylactic regimens were
      effective. Neither a 3-month course of intermittent rifapentine or rifampin with
      isoniazid nor continuous isoniazid was superior to 6 months of isoniazid. (Funded
      by the National Institute of Allergy and Infectious Diseases and others;
      ClinicalTrials.gov number, NCT00057122.).

PMID- 21732834
TI  - Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children.
AB  - BACKGROUND: The dual epidemic of human immunodeficiency virus (HIV) and
      tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We
      conducted a double-blind, randomized, placebo-controlled trial of preexposure
      isoniazid prophylaxis against tuberculosis in HIV-infected children and
      uninfected children exposed to HIV during the perinatal period. METHODS: We
      randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days
      of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or
      matching placebo for 96 weeks. All patients received bacille Calmette-Guerin
      (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected
      children had access to antiretroviral therapy. The primary outcome measures were
      tuberculosis disease and death in HIV-infected children and latent tuberculosis
      infection, tuberculosis disease, and death in HIV-uninfected children within 96
      to 108 weeks after randomization. RESULTS: Antiretroviral therapy was initiated
      in 98.9% of HIV-infected children during the study. Among HIV-infected children,
      protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the
      isoniazid group and 53 (19.3%) in the placebo group (P=0.93). Among HIV
      uninfected children, there was no significant difference in the combined
      incidence of tuberculosis infection, tuberculosis disease, or death between the
      isoniazid group (39 children, 10%) and the placebo group (45 children, 11%;
      P=0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95%
      confidence interval [CI], 95 to 153) among HIV-infected children as compared with
      41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There
      were no significant differences in clinical or severe laboratory toxic effects
      between treatment groups. CONCLUSIONS: Primary isoniazid prophylaxis did not
      improve tuberculosis-disease-free survival among HIV-infected children or
      tuberculosis-infection-free survival among HIV-uninfected children immunized with
      BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis
      remained high among HIV-infected children. (Funded by the National Institutes of
      Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.).

PMID- 21732835
TI  - Effect of nesiritide in patients with acute decompensated heart failure.
AB  - BACKGROUND: Nesiritide is approved in the United States for early relief of
      dyspnea in patients with acute heart failure. Previous meta-analyses have raised
      questions regarding renal toxicity and the mortality associated with this agent.
      METHODS: We randomly assigned 7141 patients who were hospitalized with acute
      heart failure to receive either nesiritide or placebo for 24 to 168 hours in
      addition to standard care. Coprimary end points were the change in dyspnea at 6
      and 24 hours, as measured on a 7-point Likert scale, and the composite end point
      of rehospitalization for heart failure or death within 30 days. RESULTS: Patients
      randomly assigned to nesiritide, as compared with those assigned to placebo, more
      frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs.
      42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified
      level for significance (P<=0.005 for both assessments or P<=0.0025 for either)
      was not met. The rate of rehospitalization for heart failure or death from any
      cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo
      group (absolute difference, -0.7 percentage points; 95% confidence interval [CI],
      -2.1 to 0.7; P=0.31). There were no significant differences in rates of death
      from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute
      difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening
      renal function, defined by more than a 25% decrease in the estimated glomerular
      filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21;
      P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a
      decrease in the rate of death and rehospitalization and had a small,
      nonsignificant effect on dyspnea when used in combination with other therapies.
      It was not associated with a worsening of renal function, but it was associated
      with an increase in rates of hypotension. On the basis of these results,
      nesiritide cannot be recommended for routine use in the broad population of
      patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number,
      NCT00475852.).

PMID- 21732836
TI  - A hemodynamic study of pulmonary hypertension in sickle cell disease.
AB  - BACKGROUND: The prevalence and characteristics of pulmonary hypertension in
      adults with sickle cell disease have not been clearly established. METHODS: In
      this prospective study, we evaluated 398 outpatients with sickle cell disease
      (mean age, 34 years) at referral centers in France. All patients underwent
      Doppler echocardiography, with measurement of tricuspid-valve regurgitant jet
      velocity. Right heart catheterization was performed in 96 patients in whom
      pulmonary hypertension was suspected on the basis of a tricuspid regurgitant jet
      velocity of at least 2.5 m per second. Pulmonary hypertension was defined as a
      mean pulmonary arterial pressure of at least 25 mm Hg. RESULTS: The prevalence of
      a tricuspid regurgitant jet velocity of at least 2.5 m per second was 27%. In
      contrast, the prevalence of pulmonary hypertension as confirmed on
      catheterization was 6%. The positive predictive value of echocardiography for the
      detection of pulmonary hypertension was 25%. Among the 24 patients with confirmed
      pulmonary hypertension, the pulmonary-capillary wedge pressure was 15 mm Hg or
      less (indicating precapillary pulmonary hypertension) in 11 patients. Patients
      with confirmed pulmonary hypertension were older and had poorer functional
      capacity and higher levels of N-terminal pro-brain natriuretic peptide than other
      patients. In contrast, patients who had a tricuspid regurgitant jet velocity of
      at least 2.5 m per second without pulmonary hypertension and patients with a
      tricuspid regurgitant jet velocity of less than 2.5 m per second had similar
      clinical characteristics. CONCLUSIONS: In this study of adults with sickle cell
      disease, the prevalence of pulmonary hypertension as confirmed on right heart
      catheterization was 6%. Echocardiographic evaluation alone had a low positive
      predictive value for pulmonary hypertension. (Funded by the French Ministry of
      Health and Assistance Publique-Hopitaux de Paris; ClinicalTrials.gov number,
      NCT00434902.).

PMID- 21732837
TI  - Clinical practice. Glucocorticoid-induced bone disease.

PMID- 21732838
TI  - Images in clinical medicine. Dermatologic signs of multiple myeloma.

PMID- 21732839
TI  - Clinical problem-solving. A sleeping giant.

PMID- 21732840
TI  - What is thwarting tuberculosis prevention in high-burden settings?

PMID- 21732841
TI  - The lost decade of nesiritide.

PMID- 21732842
TI  - Why do the same drugs look different? Pills, trade dress, and public health.

PMID- 21732843
TI  - Percutaneous repair or surgery for mitral regurgitation.

PMID- 21732844
TI  - Percutaneous repair or surgery for mitral regurgitation.

PMID- 21732846
TI  - Ex vivo lung perfusion in lung transplantation.

PMID- 21732848
TI  - Quality of care and negligence litigation in nursing homes.

PMID- 21732849
TI  - Quality of care and negligence litigation in nursing homes.

PMID- 21732851
TI  - Case 9-2011: A man with flushing and hypotension.

PMID- 21732852
TI  - Case 9-2011: A man with flushing and hypotension.

PMID- 21732855
TI  - Comparison of workplace protection factors for different biological contaminants.
AB  - This study compared workplace protection factors (WPFs) for five different
      contaminants (endotoxin, fungal spores, (1->3)-beta-D-glucan, total particle
      mass, and total particle number) provided by an N95 elastomeric respirator (ER)
      and an N95 filtering facepiece respirator (FFR). We previously reported size
      selective WPFs for total particle numbers for the ER and FFR, whereas the current
      article is focused on WPFs for bioaerosols and total particle mass. Farm workers
      (n = 25) wore the ER and FFR while performing activities at eight locations
      representing horse farms, pig barns, and grain handling facilities. For the
      determination of WPFs, particles were collected on filters simultaneously inside
      and outside the respirator during the first and last 15 min of a 60-min
      experiment. One field blank per subject was collected without actual sampling. A
      reporting limit (RL) was established for each contaminant based on geometric
      means (GMs) of the field blanks as the lowest possible measurable values.
      Depending on the contaminant type, 38-48% of data points were below the RL.
      Therefore, a censored regression model was used to estimate WPFs (WPF(censored)).
      The WPF(censored) provided by the two types of respirators were not significantly
      different. In contrast, significant differences were found in the WPF(censored)
      for different types of contaminants. GMs WPFs(censored) for the two types of
      respirators combined were 154, 29, 18, 19, and 176 for endotoxin, fungal spore
      count, (1->3)-beta-D-glucan, total particle mass, and total particle number,
      respectively. The WPF(censored) was more strongly associated with concentrations
      measured outside the respirator for endotoxin, fungal spores, and total particle
      mass except for total particle number. However, when only data points with
      outside concentrations higher than 176*RL were included, the WPFs increased, and
      the association between the outside concentrations and the WPFs became weaker.
      Results indicate that difference in WPFs observed between different contaminants
      may be attributed to differences in the sensitivity of analytical methods to
      detect low inside concentrations, rather than the nature of particles (biological
      or non-biological).

PMID- 21732856
TI  - Impact of three biological decontamination methods on filtering facepiece
      respirator fit, odor, comfort, and donning ease.
AB  - The objective of this study was to determine if ultraviolet germicidal
      irradiation (UVGI), moist heat incubation (MHI), or microwave-generated steam
      (MGS) decontamination affects the fitting characteristics, odor, comfort, or
      donning ease of six N95 filtering facepiece respirator (FFR) models. For each
      model, 10 experienced test subjects qualified for the study by passing a standard
      OSHA quantitative fit test. Once qualified, each subject performed a series of
      fit tests to assess respirator fit and completed surveys to evaluate odor,
      comfort, and donning ease with FFRs that were not decontaminated (controls) and
      with FFRs of the same model that had been decontaminated. Respirator fit was
      quantitatively measured using a multidonning protocol with the TSI PORTACOUNT
      Plus and the N95 Companion accessory (designed to count only particles resulting
      from face to face-seal leakage). Participants' subjective appraisals of the
      respirator's odor, comfort, and donning ease were captured using a visual analog
      scale survey. Wilcoxon signed rank tests compared median values for fit, odor,
      comfort, and donning ease for each FFR and decontamination method against their
      respective controls for a given model. Two of the six FFRs demonstrated a
      statistically significant reduction (p < 0.05) in fit after MHI decontamination.
      However, for these two FFR models, post-decontamination mean fit factors were
      still >= 100. One of the other FFRs demonstrated a relatively small though
      statistically significant increase (p < 0.05) in median odor response after MHI
      decontamination. These data suggest that FFR users with characteristics similar
      to those in this study population would be unlikely to experience a clinically
      meaningful reduction in fit, increase in odor, increase in discomfort, or
      increased difficulty in donning with the six FFRs included in this study after
      UVGI, MHI, or MGS decontamination. Further research is needed before
      decontamination of N95 FFRs for purposes of reuse can be recommended.

PMID- 21732857
TI  - Learning a sparse code for temporal sequences using STDP and sequence
      compression.
AB  - A spiking neural network that learns temporal sequences is described. A sparse
      code in which individual neurons represent sequences and subsequences enables
      multiple sequences to be stored without interference. The network is founded on a
      model of sequence compression in the hippocampus that is robust to variation in
      sequence element duration and well suited to learn sequences through spike-timing
      dependent plasticity (STDP). Three additions to the sequence compression model
      underlie the sparse representation: synapses connecting the neurons of the
      network that are subject to STDP, a competitive plasticity rule so that neurons
      specialize to individual sequences, and neural depolarization after spiking so
      that neurons have a memory. The response to new sequence elements is determined
      by the neurons that have responded to the previous subsequence, according to the
      competitively learned synaptic connections. Numerical simulations show that the
      model can learn sets of intersecting sequences, presented with widely differing
      frequencies, with elements of varying duration.

PMID- 21732858
TI  - Synchronization and redundancy: implications for robustness of neural learning
      and decision making.
AB  - Learning and decision making in the brain are key processes critical to survival,
      and yet are processes implemented by nonideal biological building blocks that can
      impose significant error. We explore quantitatively how the brain might cope with
      this inherent source of error by taking advantage of two ubiquitous mechanisms,
      redundancy and synchronization. In particular we consider a neural process whose
      goal is to learn a decision function by implementing a nonlinear gradient
      dynamics. The dynamics, however, are assumed to be corrupted by perturbations
      modeling the error, which might be incurred due to limitations of the biology,
      intrinsic neuronal noise, and imperfect measurements. We show that error, and the
      associated uncertainty surrounding a learned solution, can be controlled in large
      part by trading off synchronization strength among multiple redundant neural
      systems against the noise amplitude. The impact of the coupling between such
      redundant systems is quantified by the spectrum of the network Laplacian, and we
      discuss the role of network topology in synchronization and in reducing the
      effect of noise. We discuss range of situations in which the mechanisms we model
      arise in brain science and draw attention to experimental evidence suggesting
      that cortical circuits capable of implementing the computations of interest here
      can be found on several scales. Finally, simulations comparing theoretical bounds
      to the relevant empirical quantities show that the theoretical estimates we
      derive can be tight.

PMID- 21732859
TI  - A systematic method for configuring VLSI networks of spiking neurons.
AB  - An increasing number of research groups are developing custom hybrid
      analog/digital very large scale integration (VLSI) chips and systems that
      implement hundreds to thousands of spiking neurons with biophysically realistic
      dynamics, with the intention of emulating brainlike real-world behavior in
      hardware and robotic systems rather than simply simulating their performance on
      general-purpose digital computers. Although the electronic engineering aspects of
      these emulation systems is proceeding well, progress toward the actual emulation
      of brainlike tasks is restricted by the lack of suitable high-level configuration
      methods of the kind that have already been developed over many decades for
      simulations on general-purpose computers. The key difficulty is that the dynamics
      of the CMOS electronic analogs are determined by transistor biases that do not
      map simply to the parameter types and values used in typical abstract
      mathematical models of neurons and their networks. Here we provide a general
      method for resolving this difficulty. We describe a parameter mapping technique
      that permits an automatic configuration of VLSI neural networks so that their
      electronic emulation conforms to a higher-level neuronal simulation. We show that
      the neurons configured by our method exhibit spike timing statistics and temporal
      dynamics that are the same as those observed in the software simulated neurons
      and, in particular, that the key parameters of recurrent VLSI neural networks
      (e.g., implementing soft winner-take-all) can be precisely tuned. The proposed
      method permits a seamless integration between software simulations with hardware
      emulations and intertranslatability between the parameters of abstract neuronal
      models and their emulation counterparts. Most important, our method offers a
      route toward a high-level task configuration language for neuromorphic VLSI
      systems.

PMID- 21732860
TI  - Characterization of minimum error linear coding with sensory and neural noise.
AB  - Robust coding has been proposed as a solution to the problem of minimizing
      decoding error in the presence of neural noise. Many real-world problems,
      however, have degradation in the input signal, not just in neural
      representations. This generalized problem is more relevant to biological sensory
      coding where internal noise arises from limited neural precision and external
      noise from distortion of sensory signal such as blurring and phototransduction
      noise. In this note, we show that the optimal linear encoder for this problem can
      be decomposed exactly into two serial processes that can be optimized separately.
      One is Wiener filtering, which optimally compensates for input degradation. The
      other is robust coding, which best uses the available representational capacity
      for signal transmission with a noisy population of linear neurons. We also
      present spectral analysis of the decomposition that characterizes how the
      reconstruction error is minimized under different input signal spectra, types and
      amounts of degradation, degrees of neural precision, and neural population sizes.

PMID- 21732861
TI  - An optimal feedback control framework for grasping objects with position
      uncertainty.
AB  - As we move, the relative location between our hands and objects changes in
      uncertain ways due to noisy motor commands and imprecise and ambiguous sensory
      information. The impressive capabilities humans display for interacting and
      manipulating objects with position uncertainty suggest that our brain maintains
      representations of location uncertainty and builds compensation for uncertainty
      into its motor control strategies. Our previous work demonstrated that specific
      control strategies are used to compensate for location uncertainty. However, it
      is an open question whether compensation for position uncertainty in grasping is
      consistent with the stochastic optimal feedback control, mainly due to the
      difficulty of modeling natural tasks within this framework. In this study, we
      develop a stochastic optimal feedback control model to evaluate the optimality of
      human grasping strategies. We investigate the properties of the model through a
      series of simulation experiments and show that it explains key aspects of
      previously observed compensation strategies. It also provides a basis for
      individual differences in terms of differential control costs-the controller
      compensates only to the extent that performance benefits in terms of making
      stable grasps outweigh the additional control costs of compensation. These
      results suggest that stochastic optimal feedback control can be used to
      understand uncertainty compensation in complex natural tasks like grasping.

PMID- 21732862
TI  - Reappraisal of the somatosensory homunculus and its discontinuities.
AB  - Neuroscience folklore has it that somatotopy in human primary somatosensory
      cortex (SI) has two significant discontinuities: the hands and face map onto
      adjacent regions in SI, as do the feet and genitalia. It has been proposed that
      these conjunctions in SI result from coincident sources of stimulation in the
      fetal position, where the hands frequently touch the face, and the feet the
      genitalia. Computer modeling using a Hebbian variant of the self-organizing
      Kohonen net is consistent with this proposal. However, recent work reveals that
      the genital representation in SI for cutaneous sensations (as opposed to
      tumescence) is continuous with that of the lower trunk and thigh. This result, in
      conjunction with reports of separate face innervation and its earlier onset of
      sensory function, compared to that of the rest of the body, allows a reappraisal
      of homuncular organization. It is proposed that the somatosensory homunculus
      comprises two distinct somatotopic regions: the face representation and that of
      the rest of the body. Principles of self-organization do not account
      satisfactorily for the overall homuncular map. These results may serve to alert
      computational modelers that intrinsic developmental factors can override simple
      rules of plasticity.

PMID- 21732864
TI  - The combinatorics of neurite self-avoidance.
AB  - During neural development in Drosophila, the ability of neurite branches to
      recognize whether they are from the same or different neurons depends crucially
      on the molecule Dscam1. In particular, this recognition depends on the stochastic
      acquisition of a unique combination of Dscam1 isoforms out of a large set of
      possible isoforms. To properly interpret these findings, it is crucial to
      understand the combinatorics involved, which has previously been attempted only
      using stochastic simulations for some specific parameter combinations. Here we
      present closed-form solutions for the general case. These reveal the
      relationships among the key variables and how these constrain possible biological
      scenarios.

PMID- 21732865
TI  - A general likelihood framework for characterizing the time course of neural
      activity.
AB  - We develop a general likelihood-based framework for use in the estimation of
      neural firing rates, which is designed to choose the temporal smoothing
      parameters that maximize the likelihood of missing data. This general framework
      is algorithm-independent and thus can be applied to a multitude of established
      methods for firing rate or conditional intensity estimation. As a simple example
      of the use of the general framework, we apply it to the peristimulus time
      histogram and kernel smoother, the methods most widely used for firing rate
      estimation in the electrophysiological literature and practice. In doing so, we
      illustrate how the use of the framework can employ the general point process
      likelihood as a principled cost function and can provide substantial improvements
      in estimation accuracy for even the most basic of rate estimation algorithms. In
      particular, the resultant kernel smoother is simple to implement, efficient to
      compute, and can accurately determine the bandwidth of a given rate process from
      individual spike trains. We perform a simulation study to illustrate how the
      likelihood framework enables the kernel smoother to pick the bandwidth parameter
      that best predicts missing data, and we show applications to real experimental
      spike train data. Additionally, we discuss how the general likelihood framework
      may be used in conjunction with more sophisticated methods for firing rate and
      conditional intensity estimation and suggest possible applications.

PMID- 21732866
TI  - Condom negotiation strategy use and effectiveness among college students.
AB  - College students may engage in risky sexual behaviors, such as inconsistent
      condom use, which increase their risk of sexually transmitted infections. This
      study examined the association between six condom influence strategies (CIS) and
      reported condom use among a diverse group of college students. Differences in CIS
      and condom use were examined by gender, race or ethnicity, and relationship
      status (casual, monogamous, or no current relationship). The study also used a
      cluster analysis to investigate how the CIS were used relative to one another,
      and how patterns of CIS use were related to condom use. Results showed
      interesting differences in CIS use by gender, race or ethnicity, and relationship
      status. Four patterns of CIS usage emerged, and results suggested that using all
      CIS frequently and using more assertive CIS may be particularly important for
      increased condom use. Men reported more condom use than women overall, but
      results indicated that using CIS were especially vital for increasing condom use
      for women. Surprisingly, there were no differences in condom use found for race
      or ethnicity and relationship type. Programs aimed at increasing students' condom
      use could benefit from promoting and practicing CIS, and recognizing potential
      differences among demographic groups.

PMID- 21732867
TI  - Proximal postural control mechanisms may be exaggeratedly adopted by individuals
      with peripheral deficiencies: a review.
AB  - In quiet stance, it is understood that healthy individuals control their posture
      primarily by a peripheral mechanism for anteroposterior sway and by a proximal
      mechanism for medialateral sway. The authors proposed the hypothesis that
      patients suffering from disease-related deficiencies, at their feet and legs, may
      exaggeratedly adopt proximal control mechanisms at their hip in the
      anteroposterior and medialateral axes. They critically reviewed the literature to
      test the proximal control hypothesis against published findings. The selected
      articles analyzed postural control mechanisms in individuals with diabetic
      peripheral neuropathy and in healthy controls. The data selected were kinematic
      and electromyographic. In the anteroposterior axis, 4 authors had previously
      tested the proposed hypothesis, but the findings are contrasted. In the
      medialateral axis, one study failed to validate the tested hypothesis. Overall,
      the published studies did not conform with the proximal control hypothesis.
      However, these studies did not specifically or deeply test such a hypothesis. The
      lack of results is critical because individuals suffering from peripheral disease
      related deficiencies may be unstable, in part, because of a change in postural
      control mechanisms. For improvement of their stability and appropriate
      interventions, scientific explorations of the proximal control hypothesis should
      be investigated. Two proposals are made to move forward.

PMID- 21732868
TI  - Human supplementary motor area contribution to predictive motor planning.
AB  - The supplementary motor area (SMA) is involved in planning limb movements. An
      important component of such planning is the prediction of the sensory
      consequences of action. The authors used transcranial magnetic stimulation (TMS)
      to probe the contribution of SMA to motor planning during a predictive load
      bearing task. Single TMS pulses were delivered over the SMA after a cue
      instructing the participant to release a platform supporting his or her right
      hand, which in turn held a 2 kg mass. Participants were less able to bear the
      load successfully when TMS was delivered 400-500 ms prior to the response. This
      result suggests that the SMA contributes to the prediction of the sensory
      consequences of movement well before movement onset.

PMID- 21732869
TI  - Concordance and discordance of couples living in a rural Pakistani village:
      perspectives on contraception and abortion--a qualitative study.
AB  - In Pakistan, fertility rates and intended family size have fallen, but
      contraceptive use remains low. This has led to a high prevalence of unintended
      pregnancies, a large proportion of which result from disagreement between spouses
      about how to confront them. This study aims to understand how Pakistani couples
      view family planning, and how they communicate and make decisions surrounding
      fertility regulation. In-depth interviews were conducted with five couples and an
      additional five women and two men. Two focus groups--one for males and one for
      females--were also conducted. Family planning methods were more favoured by women
      than their husbands. Women reported the largest barrier to contraceptive use to
      be men's opposition to family planning or reproductive choices more generally, as
      well as fear of side effects of contraception. Abortion was viewed unfavourably
      except in situations of economic difficulty, having several young children or
      women's health problems. Couples reported rarely communicating about fertility
      intentions until later in childbearing after an unintended pregnancy. Discussions
      about family planning were largely initiated by women, although some felt unable
      to approach their husbands regarding this topic. Concordant intentions and
      communication between spouses led to desired pregnancy outcomes. In cases of
      discordance, women's intentions tended to determine actions and outcomes. Spousal
      communication, or the lack thereof, is an obstacle to effective contraceptive
      use, and strategies to improve couples' communication would undoubtedly enable
      them to achieve their reproductive intentions.

PMID- 21732870
TI  - An aporphine alkaloid from Nelumbo nucifera as an acetylcholinesterase inhibitor
      and the primary investigation for structure-activity correlations.
AB  - N-methylasimilobine (1), a new-found strong acetylcholinesterase (AChE)
      inhibitor, along with two weakly active aporphine alkaloids, nuciferine (2) and
      nornuciferine (3) were separated from Nelumbo nucifera. N-methylasimilobine (1)
      inhibited 50% of AChE activity at the concentrations of 1.5 +/- 0.2 ug mL(-1)
      when the standard IC(50) value of Physostigmine was 0.013 +/- 0.002 ug mL(-1).
      The mode of AChE inhibition by 1 was reversible and non-competitive. In addition,
      molecular modelling was performed to explore the binding mode of inhibitor 1 at
      the active site of AChE.

PMID- 21732871
TI  - Detection of ochratoxin A and cis- and trans-resveratrol in red wines and their
      musts from Calabria (Italy).
AB  - The natural occurrence of ochratoxin A (OTA) and cis- and trans-resveratrols in
      red wines has been widely reported. The aim of this work was to evaluate the
      ochratoxin A (OTA) and both cis- and trans-resveratrol content of red wine (from
      must to wine) in a pilot-scale vinification process in Calabria (Italy). Eleven
      samples were collected at different stages of vinification and analysis was
      carried out by HPLC. Wine from manufacturer 3 contained the highest amount of
      trans-resveratrol (3.41 mg l(-1)). This wine was characterized by an Aglianico
      Magliocco grape variety. Interestingly, data regarding OTA showed that the value
      of this contaminant was low in all analyzed samples and, in each case, below the
      legal limit (2.0 mg l(-1) (ppb)). Overall, the results demonstrated the high
      quality of wines produced in Calabria.

PMID- 21732872
TI  - Transfer, viability and colonisation of Campylobacter jejuni in the chicken
      vitellus and in embryos.
AB  - 1. The objective of this study was to evaluate the ability of Campylobacter
      jejuni to penetrate and colonise eggs from specific-pathogen-free (SPF) and heavy
      breeder hens, and to determine its effects on the viability of SPF embryos. 2. We
      detected C. jejuni in 10% of breeder hens and 20% of SPF eggs, which demonstrates
      the ability of the bacteria to go through the pores of eggs and contaminate the
      vitellus after 3 h of contact. These results indicate that there is a risk of
      contamination under commercial production conditions, where, after oviposition,
      there is contact between the egg and organic material such as faeces and blood.
      3. We observed that in 80% of SPF eggs analysed, C. jejuni survived the 21-d
      incubation period. This positive result suggests that this microorganism was also
      responsible for early embryonic mortality. 4. The ability of C. jejuni to
      penetrate the eggs in this study suggests that serious problems may occur under
      natural field conditions, which may cause significant problems for producers.

PMID- 21732873
TI  - Exogenous DNA internalisation by sperm cells is improved by combining lipofection
      and restriction enzyme mediated integration.
AB  - 1. Three types of exogenous DNA inserts, i.e. complete linearised pVIVO2-GFP/LacZ
      vector (9620 bp), the LacZ gene (5317 bp) and the GFP gene (2152 bp) were used to
      transfect chicken spermatozoa through simple incubation of sperm cells with
      insert. 2. PCR assay, Dot Blot hybridisation and Southern hybridisation showed
      the successful internalisation of exogenous DNA by chicken sperm cells. 3.
      Lipofection and Restriction Enzyme Mediated Integration (REMI) were used to
      improve the rate of internalisation of exogenous DNA by sperm cells. 4. Results
      from dot blot as well as Southern hybridisation were semi-quantified and improved
      exogenous DNA uptake by sperm cells through lipofection and REMI. Stronger
      signals were observed from hybridisation of LacZ as well as GFP specific probe
      with the DNA from lipofected exogenous DNA transfected sperm DNA in comparison
      with those transfected with nude exogenous DNA.

PMID- 21732874
TI  - Sodium butyrate maintains growth performance by regulating the immune response in
      broiler chickens.
AB  - 1. The experiment was conducted to investigate the effects of dietary sodium
      butyrate on the growth performance and immune response of broiler chickens. In
      experiment 1, 240 1-d-old chickens were allocated into 4 dietary groups (0, 0.25,
      0.50 or 1.00 g sodium butyrate/kg) with 6 replicates each. In experiment 2, 120 1
      d-old chickens were fed a control diet (without sodium butyrate) or 1.00 g sodium
      butyrate/kg diet. Half of the chickens fed on each diet were injected intra
      peritoneally with 0.5 g/kg body weight of Escherichia coli lipopolysaccharide
      (LPS) at 16, 18 and 20 d of age. 2. There was no effect of dietary sodium
      butyrate on growth performance. On d 21, serum interleukin-6 (IL-6) and tumour
      necrosis factor-alpha (TNF-alpha) were decreased in chickens given 1.00 g sodium
      butyrate/kg, serum superoxide dismutase (SOD) and catalase activities were
      significantly increased, and malondialdehyde (MDA) was decreased by dietary
      sodium butyrate at 0.50 or 1.00 g/kg. On d 42, serum IL-6 was markedly decreased
      by dietary sodium butyrate, while 1.00 g sodium butyrate/kg greatly reduced MDA
      and increased catalase. 3. LPS challenge significantly reduced the growth
      performance of chickens. Serum IL-1beta, IL-6, TNF-alpha, corticosterone, alpha-1
      acid glycoprotein (AGP) and prostaglandin E(2) (PGE(2)) were increased in LPS
      challenged chickens. Dietary sodium butyrate supplementation maintained the body
      weight gain and feed intake. Sodium butyrate supplementation inhibited the
      increase in IL-6 and AGP in serum at 16 d of age and TNF-alpha, corticosterone,
      AGP and PGE(2) at 20 d of age. Similar inhibitory effects of sodium butyrate in
      serum glucose and total protein concentrations were also found at 20 d of age. 4.
      The results indicated that dietary sodium butyrate supplementation can improve
      the growth performance in chickens under stress and that this may be used to
      moderate the immune response and reduce tissue damage.

PMID- 21732875
TI  - Effects of dietary polysavone (Alfalfa extract) and chlortetracycline
      supplementation on antioxidation and meat quality in broiler chickens.
AB  - 1. A total of 360 1-d-old male commercial Arbor Acre broiler chickens were
      randomly assigned to 5 groups (6 replicates of 12 birds each) to evaluate the
      dietary effects of polysavone (0.5, 1.0 and 1.5 g/kg), a natural extract from
      alfalfa, and 0.15 g/kg chlortetracycline (CTC) on growth performance,
      antioxidation and meat quality of broiler chickens. 2. Over the 6-week study,
      feed intake increased significantly with CTC supplementation and final body
      weight (BW) was significantly higher for 1.0 g/kg polysavone and 0.15 g/kg CTC
      treatments. Feed:gain ratio was not significantly affected by the dietary
      treatments. 3. At 3 weeks of age, serum total superoxide dismutase (T-SOD)
      activity for all polysavone treatments was significantly higher than controls,
      liver T-SOD activity in 1.5 g/kg polysavone group was significantly higher than
      the control and CTC groups, and serum glutathione peroxidase (GSHPx) activity for
      1.5 g/kg polysavone and liver GSHPx activity in all polysavone groups were
      significantly higher than CTC. 4. At 6 weeks of age, serum and liver T-SOD
      activity in 1.5 g/kg polysavone group and liver GSHPx activity for all polysavone
      treatments were higher significantly than the control and CTC groups, and serum
      malondialdehyde (MDA) content for all polysavone treatments was significantly
      lower than CTC. 5. Breast muscle T-SOD activity and pH value at 6 weeks of age
      were significantly higher and MDA content was significantly lower in 1.0 and 1.5
      g/kg polysavone groups than in the control and CTC groups. Breast muscle shear
      force was significantly lower in l.5 g/kg polysavone group compared with the
      control, and drip loss for all polysavone treatments was significantly lower than
      CTC. 6. It was indicated that polysavone modulates antioxidation and modifies
      meat quality, but with no adverse effect on performance of broiler chickens, and
      that CTC can be beneficial to performance but has no beneficial effect on
      antioxidant function or meat quality.

PMID- 21732876
TI  - Effects of caponisation on lipid and fatty acid composition of intramuscular and
      abdominal fat of medium-growth broilers.
AB  - 1. Capons and intact male broilers were used to investigate the effects of
      caponisation on intramuscular fat and abdominal adipose tissue lipid content and
      fatty acid profile. 2. Capons had significantly higher total lipid content
      (P<0.05). 3. Neutral lipids were the major fractions in intramuscular and
      abdominal fat but their proportions differed significantly among groups and
      tissues (P<0.05). 4. The predominant saturated, monounsaturated and
      polyunsaturated fatty acids in all samples were C16:0, C16:1 omega-9, C18:0,
      C18:1 omega-9, C18:1 omega-7, C18:2 omega-6 and C20:4 omega-6. 5. Caponisation
      resulted in a significant omega-6/omega-3, PUFA and PUFA/SFA ratio reduction as
      well as a significant increase in atherogenic and thrombogenic indices increase
      in intramuscular fat (P<0.05) without affecting their appropriate value for a
      healthy diet.

PMID- 21732877
TI  - Molecular cloning, polymorphism and tissue distribution of the MHC class IIB gene
      in the Chinese goose (Anser cygnoides).
AB  - 1. The goose major histocompatibility complex (MHC) class IIB cDNA (Ancy-MHCII)
      was cloned by homology cloning and rapid amplification of cDNA ends by polymerase
      chain reaction (RACE-PCR), and the genomic structure and tissue expression were
      investigated. 2. Three different 5'-RACE sequences (Ancy-MHC II5'-1, Ancy-MHC
      II5'-2, Ancy-MHC II5'-3), one 3'-RACE sequence (Ancy-MHC II-3') and two different
      full length Ancy-MHC IIB cDNA sequences (Ancy-CD01, Ancy-CD02), which came from
      different alleles at one locus or different loci, were determined. 3. The genomic
      organisation is composed of 6 exons and 5 introns, with a longer intron region
      than that of the chicken. The alleles encode 259 and 260 amino acids in the
      mature protein. 4. The number of non-synonymous substitutions (dN) in the peptide
      binding region of exon 2 from 8 alleles was higher than that of the synonymous
      substitutions (dS). 5. Tissue-specific expression of Ancy-MHC II mRNA was
      detected in an adult goose using RT-PCR. These results showed that Ancy-MHC II
      mRNA was expressed in the lung, spleen, liver, intestine, heart, kidney,
      pancreas, brain, skin and muscle. This is consistent with the expression of MHC
      class IIB in various tissues from the chicken. 6. Sequences from goose, snipe and
      duck clustered together when compared with known MHC class IIB sequences from the
      other species, significantly differing from mammals and aquatic species,
      indicating a pattern consistent with accepted evolutionary pathways.

PMID- 21732878
TI  - Association of polymorphisms for nuclear receptor coactivator 1 gene with egg
      production traits in the maternal line of Shaobo hens.
AB  - 1. The objectives of the study were to find polymorphic sites and elucidate the
      association between SNPs in the nuclear receptor coactivator 1 (NCOA1) gene and
      reproductive traits. 2. SNPs were detected by PCR-SSCP and DNA sequencing. Four
      SNPs were detected, including T10155007A, T10125838C, G10118492A and G10109315T.
      Three polymorphisms were associated with total egg production at the age of 300 d
      and the G10109315T polymorphism was associated with age at first egg. 3. In
      conclusion, the NCOA1 gene can be used as a molecular marker for reproductive
      traits in hens.

PMID- 21732879
TI  - Impacts of dried whole eggs on productive performance, quality of fresh and
      stored eggs, reproductive organs and lipid metabolism of laying hens.
AB  - 1. Rejected eggs were processed by freezing, freezing and boiling, or
      autoclaving, dried at 55 degrees C, and the chemical and amino-acid analysis and
      microbiological properties of the dried whole eggs (DWE) determined. The
      processed DWE was included in a laying-hen mash diet at 50 or 100 g/kg, mainly to
      replace soybean meal and maize, in a factorial design of 3*2 and fed to hens
      between 25 and 41 weeks of age. In addition, a control diet without DWE was used
      to create a total of 7 treatments; each having 5 replicates of 5 hens. 2. Hens
      fed the diet containing 50-g/kg frozen and boiled DWE and 100-g/kg frozen DWE
      laid the largest egg size, while hens fed the 50-g/kg frozen and boiled or
      autoclaved DWE diets yielded the highest egg mass and best feed conversion
      efficiency. 3. Hens fed the 50-g/kg frozen DWE laid eggs with a higher yolk
      indices, Haugh unit scores, and eggshell thickness and maintained higher Haugh
      unit scores during egg storage. 4. Yolk cholesterol significantly decreased in
      eggs from groups fed either the 50-g/kg frozen or autoclaved DWE diet, with
      freezing having the stronger effect. 6. In conclusion, 50-g/kg autoclaved DWE
      diets fed to laying hens between 25 and 41 weeks of age had no adverse effects on
      production, egg quality or reproductive organs, but decreased yolk cholesterol,
      and thus could be beneficially included in laying-hen diets.

PMID- 21732880
TI  - Effects of rice husk diluted dietary switching on the phenotypic change of
      gastrointestinal tract in adult ganders.
AB  - 1. An experiment was conducted to test the directionality, scaling and
      reversibility of phenotypic responses of the gastrointestinal tract (GIT) of
      adult ganders to rice husk (RH) diluted dietary switching. 2. A total of 96 140-d
      old ganders were acclimatised to a basal diet for 2 weeks. The birds were
      randomly assigned to 4 treatments. On d 1, diets in the experimental groups were
      switched from the basal diet to diets which contained 200, 400 or 600 g/kg RH by
      mass, with no RH in the basal diet. After 21 d, the diet of all the experimental
      birds was switched back to the basal diet until d 42. 3. Increasing RH content
      significantly increased feed intake, and a decreased trend appeared after diet
      switching. The weights of geese fed on the 600 g/kg RH diet for 21 d reduced, and
      were significantly less than those of the other three groups, while body weights
      (BW) of the geese in all groups increased after diet-switching back to the basal
      diet. At d 21, significantly heavier relative weights of proventriculus, gizzard
      and all gut components, except duodenum, were observed in birds fed on a 600 g/kg
      RH diet, and significantly heavier relative weights of gizzard were observed in
      birds given a 400 g/kg RH diet. Thickness of the two gastric walls, gizzard
      length and all gut components lengths increased significantly in birds given a
      600 g/kg RH diet compared with the other three groups. At d 42, no significant
      differences were noted in the relative weights or lengths of GIT, except for the
      caeca, which were significantly heavier in birds fed on 600 g/kg RH diet. 4. The
      results of the experiment were in accordance with the predictions of the
      hypothesis that there is matching between loads and capacities. The observed
      phenotypic responses were directional and scaled to the demands.

PMID- 21732881
TI  - Effects of different rearing and feeding methods on meat quality and
      antioxidative properties in Chinese Yellow male broilers.
AB  - 1. This study examined responses of male broilers during a 42-d production cycle
      to two different rearing and feeding methods. 2. A total of 400 Chinese Yellow
      male broilers were allotted randomly at 21 d into two groups; the control was a
      typical indoor commercial rearing method and the treatment had outdoor access
      with scattered feeding (OS). Each group had 5 replicates with 40 birds per
      replicate. 3. Growth performance was similar for both groups from 21 to 63 d of
      age. OS birds had significantly lower abdominal fat percentage, meat shear force,
      drip loss, breast meat colour b* value and significantly higher pH value compared
      with the controls. OS birds had significantly lower muscle fibre diameter and
      greater muscle fibre density. Serum glutathione peroxidase and catalase
      activities were significantly higher and the contents of cholesterol, lactic
      acid, glycogen and malondialdehyde of breast muscle were significantly lower in
      OS birds than controls. 4. The results suggest that the OS feeding method had no
      negative effects on performance (weight, gain, feed conversion rate, carcase
      traits) compared with controls, and appeared to be beneficial for meat quality
      indices and oxidative stability.

PMID- 21732882
TI  - Effect of trypsin inhibitor activity in soya bean on growth performance, protein
      digestibility and incidence of sub-clinical necrotic enteritis in broiler chicken
      flocks.
AB  - 1. The effect of three different levels of dietary trypsin inhibitor activity
      (achieved by varying the amount of non-toasted full fat soya bean in replacement
      for toasted full fat soya bean) on the incidence of spontaneously-occurring sub
      clinical necrotic enteritis (NE) in broiler chickens was compared. A fourth
      dietary treatment compared the effect of a diet that used potato protein
      concentrate as the major protein source. The determined trypsin inhibitor
      activity increased with the increasing content of non-toasted soya bean: 1.90,
      6.21, 8.46 and 3.72 mg/g for the three soya bean diets (0, 100 and 200 g of non
      toasted soya bean/kg) and the potato protein diet respectively. 2. Although
      increasing amounts of the non-toasted full-fat soya bean increased the feed
      intakes of the birds, there was a marked reduction in protein digestibility,
      weight gain and feed conversion efficiency. 3. There was a linear increase in sub
      clinical NE lesions in the duodenum, jejunum, mid small intestine and ileum with
      increasing non-toasted soya bean. Caecal Clostridium perfringens counts increased
      with the increasing dietary content of non-toasted soya bean. Serum alpha-toxin
      antibodies were higher in the birds fed the 200 g non-toasted soya bean/kg diet
      compared with the other diets. 4. The results demonstrated that variation in the
      amount of non-toasted dietary soya bean not only affects growth performance of
      broilers but also affects the incidence of sub-clinical necrotic enteritis in the
      flock. Ensuring the lowest possible trypsin-inhibitor activity in soya bean
      samples is a valuable tool to improve the health and welfare of birds and in
      reducing the financial losses from this disease.

PMID- 21732883
TI  - The effect of glycerol inclusion on broiler performance and nutrient
      digestibility.
AB  - 1. Crude glycerol from biodiesel production was offered ad libitum to broiler
      chickens in a 21-d feeding and digestibility trial. The study was designed as a
      3*2 + 1 factorial design with 3 concentrations (33, 67, 100 g/kg) of glycerol
      from 2 sources, A and B (PRS Environmental Ltd and John Thompson and Sons Ltd)
      and a control diet. The diets were formulated to contain apparent metabolisable
      energy (AME) of 12.95 MJ/kg (assuming 14.6 MJ/kg for glycerol). 2. No significant
      interactions occurred, so only the main effects were discussed. At 7-14 d, feed
      conversion ratio (FCR) showed a significant linear response with increased
      glycerol inclusion. However quadratic responses on FCR were observed for the 21
      28 d period and 7-28 d. 3. Glycerol digestibility was significantly greater with
      birds offered the 67 g/kg and 100 g/kg glycerol-based diets in contrast to the
      digestibility of 33 g/kg glycerol-based diets. 4. Glycerol inclusion level also
      had an effect on AME, which increased linearly with increasing glycerol
      inclusion. Birds offered the diets containing glycerol also required less energy
      per unit gain in contrast to birds offered the control diet. 5. When examining
      the effect of source of glycerol, source A glycerol resulted in the highest AME
      (15.20 vs. 14.72 MJ/kg). There was no significant effect of glycerol source on
      the other performance parameters. 6. Glycerol digestibility was significantly
      greater with glycerol from source B (John Thompson and Sons, Ltd) with a mean
      value of 0.848 in contrast to source A (PRS Environmental), which had a somewhat
      lower mean glycerol digestibility of 0.757. 7. In conclusion, glycerol source did
      not affect performance and increasing level of glycerol improved FCR, with 67
      g/kg inclusion resulting in the most efficient conversion of feed to gain without
      any negative effects upon nutrient digestibility.

PMID- 21732884
TI  - Kinetic modelling and residue depletion of drugs in eggs.
AB  - 1. A physiologically-based pharmacokinetic model was developed for the purpose of
      describing the relationship between plasma concentration of drugs and their
      deposition into eggs. 2. By incorporating the physiology of egg formation into
      the model, the transfer of drugs into the egg albumen and yolk could be described
      using rate constants. 3. The model was used to describe concentrations in albumen
      and yolk of sulphanilamide, sulphaquinoxaline and pyrimethamine as a function of
      time using datasets from the literature. 4. The model could be used as a tool to
      obtain an insight into those properties of a drug which are responsible for the
      amount of residue in eggs, and could help in the design of critical studies for
      determining withdrawal periods for eggs.

PMID- 21732885
TI  - Effects of perilla extract on productive performance, serum values and hepatic
      expression of lipid-related genes in Shaoxing ducks.
AB  - 1. The aim of this study was to identify the effect of perilla extract, a source
      of polyunsaturated fatty acids, on lipid metabolism and expression of lipid
      related genes in livers of Shaoxing ducks. 2. Two hundred and forty 28-week-old
      laying ducks received a commercial diet with perilla extract added at 0 (control)
      or 200 mg/kg of feed. 3. Ducks fed on a diet with perilla extract had increased
      laying rates compared with control ducks. 4. Serum concentrations of
      triglycerides were reduced by perilla extract, while high-density lipoprotein
      cholesterol and total serum cholesterol increased. 5. The expression of genes
      involved in hepatic lipogenesis, sterol regulatory element-binding protein-1,
      acetyl CoA carboxylase, stearoyl CoA desaturase, fatty acid synthase,
      apolipoprotein B, and apolipoprotein very low density lipoprotein, were decreased
      in the perilla group. 6. The mRNA expression of peroxisome proliferators
      activated receptor alpha and acyl-coenzyme A oxidase was enhanced following
      treatment with perilla extract, and a similar tendency was observed in the
      expression of liver fatty acid-binding protein. 7. The results show that a diet
      with 200 mg/kg perilla extract regulated fat metabolism of Shaoxing ducks by
      improving egg laying, altering serum lipid profiles, stimulating lipid catabolic
      gene expression and inhibiting lipogenic gene expression in the liver.

PMID- 21732886
TI  - Effect of oxygen supplementation in the hatcher at high altitude on the
      incubation results of broiler eggs laid at low altitude.
AB  - 1. The object of this research was to investigate the effects of high altitude
      with supplementary oxygen during the last stage of incubation of broiler eggs
      laid at low altitude and incubated at low and high altitude. We analysed thyroid
      hormones and haematological variables. 2. The treatment groups were: low altitude
      (LA), high altitude with oxygen supplementation in the hatcher (HA-OX) and high
      altitude non-oxygen-supplemented (HA-NOX). 3. High altitude affected relative egg
      weight loss and early embryonic mortality. The hatchability of fertile eggs was
      lower at high than at low altitude. 4. Oxygen supplementation into the hatcher
      cabinet during the last stage of incubation decreased late embryonic mortality
      ratio (LEM(1)) and improved survival rates of embryos incubated at high altitude.
      5. Eggs incubated at low altitude had a higher hatched chick weight and relative
      chick weight than those incubated at high altitude. Hatched chick weight and
      relative chick weight did not change with oxygen supplementation at high
      altitude. 6. High altitude caused an increase in plasma T(3) and T(4)
      concentrations as well as in the ratio of T(3):T(4) in embryos. High altitude
      newly hatched chicks showed a higher T(3):T(4) ratio than low altitude chicks;
      this ratio decreased with oxygen supplementation at high altitude. Altitude and
      oxygen supplementation did not affect the mean plasma T(4). 7. Newly-hatched
      chicks incubated at high altitude showed a higher plasma haematocrit (PCV) than
      the newly-hatched chicks from eggs incubated at low altitude. High altitude
      without supplementation increased haemoglobin (Hb), while oxygen supplementation
      returned the value to low altitude values.

PMID- 21732887
TI  - Influence of chicken native breeds on some physical and biochemical
      characteristics and short-term storage of semen.
AB  - 1. The major objective of this study was to examine the influence of 24-h storage
      of semen at low temperature on semen characteristics and fertilising ability of
      spermatozoa in two native breeds (Kadaknath-KN, Aseel Peela-AP) and White Leghorn
      (WL) chicken. 2. Various physical and biochemical properties of freshly
      ejaculated semen of KN and AP were investigated. Fertility was examined in
      freshly-ejaculated as well as 24-h-stored (3 degrees C) semen diluted (1:3) with
      Beltsville Poultry Semen Extender. 3. No significant difference was observed in
      sperm motility among the different breeds whereas live counts were higher in WL
      than the native breeds. Body weight, semen volume and sperm concentration were
      highest in AP, followed by KN and WL. A similar trend was observed in the
      percentage of dead and morphologically-abnormal spermatozoa. 4. The activity of
      acid and alkaline phosphatase in seminal plasma were higher in WL than KN,
      whereas the opposite trend was recorded for glutamic oxaloacetic and pyruvic
      transaminases. The cholesterol content of semen was highest in AP, followed by KN
      and WL. Cholesterol was much lower in seminal plasma compared with whole semen
      but there were no differences between breeds. Mean values of the methylene blue
      reduction time test were higher in WL than in the native breeds. 5. Fertility and
      hatchability, using freshly-diluted semen, were poorer in the native breeds than
      in WL. The pattern of fertility deteriorated further, especially in native fowls,
      when the birds were inseminated with 24-h-stored semen. 6. In conclusion,
      variation in physical and biochemical characteristics of semen in native breeds
      compared to WL correlated with poor fertility after short-term storage of semen.

PMID- 21732889
TI  - Prenatal diagnostics in TESA/PESA pregnancies in Denmark 1995-2007: a shift from
      invasive procedures to nuchal translucency examination.
AB  - Evidently, children born after intracytoplasmic sperm injection (ICSI) are at an
      increased risk of having sex chromosomal abnormalities. Here we evaluate the
      change in methods used for prenatal diagnostics in patients having ICSI with
      epididymal or testicular sperm from the introduction of the procedure in 1995
      until December 2007. Four hundred and fifty pregnancies resulted in the birth of
      553 children. Of the Danish subpopulation 115 (34.2%) received nuchal
      translucency examination (NT) and 43 (12.8%) received invasive prenatal
      diagnostics (IPD). IPD was carried out in 11 out of 23 couples (48%) during the
      period 1995-1998. Since 2002, less than 10% chose to receive IPD. Twenty-one
      (57%) of 37 Danish women 37-44 years of age underwent IPD compared to only 22
      (7.4%) of the 299 women less than 37 years of age (p < 0.001). Conversely, since
      1999 the use of NT has gradually increased to a frequency of 88.9% in 2007. The
      partners of vasectomized men had significantly more often NT performed compared
      to those of non-vasectomized men. IPD were not otherwise associated with the
      etiology of azoospermia. This study documents a shift in prenatal diagnostics
      from IPD to NT for testicular sperm aspiration/percutaneous epididymal sperm
      aspiration (TESA/PESA) couples.

PMID- 21732890
TI  - The position of the fertility counsellor in a fertility team: a critical
      appraisal.
AB  - The ongoing evolution of reproductive medicine has revealed the complexity of
      emotional reactions of couples seeking to fulfil their desire for a child. The
      position of counselling is evaluated from three perspectives: the couple, medical
      staff and the individual counsellor. This leads to three proposed levels of
      counselling, as an integrated component of Assisted Reproductive Technology
      (ART).

PMID- 21732891
TI  - Are prior pregnancy outcomes relevant for models of fertility-specific distress
      or infertility helpseeking?
AB  - Women with prior pregnancy but no live birth are inconsistently termed as either
      'primary infertile' or 'secondary infertile' in psychosocial studies of infertile
      women. The goal of this study was to discover whether infertile women who had
      experienced pregnancies but no live births were more similar in attitudes and
      behaviour to infertile women who had not experienced pregnancies or to those who
      had live births. We used the National Survey of Fertility Barriers (NSFB), which
      contains self-reported data from a probability-based sample of US women aged
      between 25 and 45, to accomplish our goal. In this cross-sectional analysis,
      infertile women who had not experienced pregnancies were compared on the basis of
      fertility-specific distress (FSD) and medical help-seeking for infertility to
      women who had had pregnancies with live births and women with pregnancies but no
      live births. Women were interviewed by telephone in their homes. Data of 1,027
      women who had had an infertility episode within the past 10 years were analysed
      using multiple regression and logistic regression. Infertile women who had never
      been pregnant experience higher levels of FSD and were more likely to seek
      treatment than infertile women who had been pregnant, regardless of the outcome
      of the pregnancy.

PMID- 21732892
TI  - QSAR studies on the depuration rates of polycyclic aromatic hydrocarbons,
      polybrominated diphenyl ethers and polychlorinated biphenyls in mussels (Elliptio
      complanata).
AB  - Based on the mechanism of action, a quantitative structure-activity relationship
      (QSAR) model for the depuration rate constants (k(d)) of 28 PAHs, 8 PBDEs and 28
      PCBs in mussels (Elliptio complanata) was constructed by partial least squares
      (PLS) regression, following the guidelines for development and validation of QSAR
      models. For the training set of the QSAR model, r2 = 0.953, the cross-validated
      regression coefficient (Q2(CUM)) was 0.947. The predicted log k(d) values for the
      validation set were consistent with the observed values, with a standard error
      (SE) of 0.160 log units and a squared correlation coefficient (Q2(EXT)) of 0.892.
      Comparatively, the developed QSAR model had good robustness, predictive ability
      and extended applicability domain. The electrophilicity index (omega), molecular
      polarizability (alpha), the averages of the negative potentials on the molecular
      surface (V(s-)) and the balance parameter of surface potential (tau) were the key
      parameters governing the log k(d) values in the QSAR model, which indicated that
      the log k(d) value was mainly related to the partition ability, electrostatic
      interactions, and van der Waals interactions of compounds.

PMID- 21732893
TI  - Internal and external validation of the long-term QSARs for neutral organics to
      fish from ECOSARTM.
AB  - This study concentrates on the external validation of an existing Quantitative
      Structure-Activity Relationship (QSAR) model widely used for long-term aquatic
      toxicity to fish. In the context of the REACH legislation, QSARs are used as an
      alternative for experimental data to achieve a complete environmental assessment
      without the need for animal testing. The predictivity of the model was evaluated
      in order to increase the reliability of the model. We assessed whether the model
      met all of the OECD principles. The model was adapted to become more robust, and
      predictions were made with an external validation set collected from several
      databases. For the internal validation of the QSAR, the r2, Q2(Loo) and Q2(LMO)
      were used as validation criteria, and for the external validation r2, Q2(ext), h
      and the validation ratio were used. A few substances were classified as outliers
      and therefore the applicability domain of the QSAR had to be adjusted. The QSAR
      passed all validation criteria and met all the OECD principles for QSAR
      validation, and the long-term toxicity QSAR for fish can be applied with high
      certainty of a correct prediction within the limits of the inherent uncertainty
      of the model in cases where the substance falls within the applicability domain.

PMID- 21732894
TI  - Treatment of advanced HIV disease in antiretroviral-naive HIV-1-infected patients
      receiving once-daily atazanavir/ritonavir or twice-daily lopinavir/ritonavir,
      each in combination with tenofovir disoproxil fumarate and emtricitabine.
AB  - Current guidelines for HIV therapy recommend initiating treatment at a CD4 cell
      count of 500 cells/mm(3). However, a large proportion of patients with HIV
      infection begin antiretroviral treatment at a more advanced stage. In the CASTLE
      study, patients with the most advanced HIV disease (CD4 cell count <50
      cells/mm(3)) showed that 78% (45/58) vs. 58% (28/48) of the patients achieved HIV
      RNA <50 copies/mL in the intent-to-treat analysis at week 96 for
      atazanavir/ritonavir and lopinavir/ritonavir, respectively. This current sub
      analysis of the CASTLE study describes demographics, virologic failure,
      discontinuations, safety, tolerability, immunologic response, and clinical
      outcomes for the following baseline strata: CD4 cell count (cells/mm(3)) <50, 50
      to <100, 100 to <200, and >=200 and HIV RNA (copies/mL) <100,000, 100,000 to
      <500,000, and >=500,000. In the lowest CD4 cell count stratum (<50 cells/mm(3)),
      the proportion of discontinuations was 2-fold greater for the lopinavir/ritonavir
      arm (33%) than for the atazanavir/ritonavir arm (16%) with a similar rate of
      virologic failure between the two groups. Also in this CD4 cell count stratum,
      grades 2-4 treatment-related adverse events occurred in 25% in the
      atazanavir/ritonavir group and in 43% of lopinavir/ritonavir group, and the rate
      was also higher than in the higher CD4 cell count strata within the
      lopinavir/ritonavir treatment group (range: 29-34%). Grades 2-4 treatment-related
      diarrhea and nausea occurred in more patients receiving lopinavir/ritonavir than
      atazanavir/ritonavir in all strata. The atazanavir/ritonavir group had more
      grades 2-4 treatment-related jaundice than in the lopinavir/ritonavir group.
      These results highlight the importance of tolerability of antiretroviral therapy
      (ART) in the patients at greatest risk of morbidity and mortality when using
      regimens of similar potency.

PMID- 21732895
TI  - Predictors of HIV positivity among pregnant women presenting for obstetric care
      in South India - a case-control study.
AB  - Feminization of the HIV epidemic in India has increasingly burdened the public
      health infrastructure to provide prevention of mother-to-child transmission
      (PMTCT) services. A mere 20% of pregnant women in the country receive HIV
      counseling and testing. One of the strategies, for expansion of PMTCT services is
      to ascertain an accurate identification of HIV-positive pregnant women. Thus, we
      sought to characterize a demographic profile of pregnant women at high-risk for
      HIV infection. We performed a retrospective case-control study. We included as
      cases, all HIV-positive women identified in a PMTCT program implemented in 23
      charitable faith-based hospitals in four states in South India over a period of
      75 months, starting in January 2003. Thus a total of 320 HIV-positive cases were
      frequency matched using stratified random sampling to 365 HIV-negative pregnant
      women presenting for antenatal care during the same time period. Cases and
      controls were compared using Chi-square test for categorical variables and
      Student's t-test for continuous variables. Multivariate step-wise logistic
      regression analysis was performed. On multivariate analysis, following factors
      were independently predictive of HIV positivity: age <=25 years (odds ratio [OR]
      0.50; confidence interval [CI] 0.33-0.76; p = 0.001); illiteracy (OR 4.89; CI
      2.79-8.57; p <0.0001); woman holding a service and/or professional job (OR 0.27;
      CI 0.14-0.53; p <0.0001); spouses holding a service or higher job (OR 3.13; CI
      2.13-4.59; p <0.0001); being married <=5 years (OR 2.89; CI 1.68-4.95; p
      <0.0001); late gestational age at presentation (OR 3.06; CI 2.04-4.59; p
      <0.0001); history of fetal and/or live born loss (OR 2.36; CI 1.51-3.67; p
      <0.0001). To our knowledge this is the first large study to evaluate factors
      predictive of HIV positivity among women presenting for antenatal care in the
      Indian setting. This type of profiling of HIV-positive pregnant women may help
      expand PMTCT services in a focused and cost-effective manner in India.

PMID- 21732896
TI  - Sexual risk behavior among HIV-positive patients at an urban clinic in Santiago,
      Dominican Republic.
AB  - More than 1% of adults in the Dominican Republic are HIV-infected and most
      infections are acquired sexually. We studied sexual risk behaviors in a group of
      HIV-positive patients treated in Santiago, Dominican Republic.   Interviews were
      conducted with 129 participants seen in May 2006 at one of the country's largest
      public hospital HIV clinics. Questions included demographics, sexual history,
      condom use, and focused on patients' last sexual encounter.   Most patients
      (72.4%) had been sexually active since their HIV diagnosis. Following their
      diagnosis, 72.8% of sexually active patients used condoms more frequently, 21.7%
      used condoms with the same frequency, and 5.4% used condoms less often. The most
      common reason cited for not using a condom after HIV diagnosis differed by
      gender; men cited decreased sexual pleasure (70.0%) and women reported that their
      partner had refused to use a condom (71.8%). Sexually active patients who
      believed that their partner did not have HIV were much more likely to report
      using a condom at their last sexual encounter than those who did not know their
      partner's HIV status (odds ratio [OR] = 16.9).   HIV-positive patients reported
      using condoms more frequently following their HIV diagnosis and were more likely
      to use a condom if they believed their partner did not have HIV. Increased HIV
      testing may lead to reduced sexual risk behavior in the Dominican Republic.

PMID- 21732897
TI  - Acceptance-based behavior therapy to promote HIV medication adherence.
AB  - A significant number of adults with HIV in the USA do not maintain adherence to
      highly active antiretroviral therapy (HAART) at adequate levels. Although
      traditional cognitive behavioral interventions have shown promise in promoting
      HAART adherence, acceptance-based behavior therapy (ABBT) may be particularly
      useful in this population. ABBT has the potential to overcome common avoidance
      based barriers associated with poor adherence, including denial of various
      illness-related factors and avoidance of stigmatization. We describe the
      rationale for promoting psychological and behavioral acceptance in HIV-positive
      populations; outline an ABBT to promote HAART adherence targeting primary care
      patients from urban, minority, low socioeconomic backgrounds; and report
      preliminary qualitative observations of treatment feasibility and acceptability.

PMID- 21732898
TI  - The development of a screening tool to evaluate gross motor function in HIV
      infected infants.
AB  - Neurodevelopmental delay or HIV encephalopathy is a stage four disease indicator
      for paediatric HIV/AIDS according to the World Health Organisation (WHO), and may
      be used as a criterion for initiation of highly active antiretroviral therapy
      (HAART). To date, the only means of prevention of this condition is early
      initiation of HAART. Studies which have been carried out in South African clinics
      have revealed the high prevalence of this condition. In developing countries,
      commencement of HAART is based on declining virologic and immunologic status, as
      standardised neurodevelopmental assessment tools are not widely available. A
      standardised developmental screening tool which is suitable for use in a
      developing country is therefore necessary in order to screen for
      neurodevelopmental delay to allow for further assessment and referral to
      rehabilitation services, as well as providing an additional assessment criterion
      for initiation of HAART.   The infant gross motor screening test (IGMST) was
      developed for this purpose. The standardisation sample of the IGMST consisted of
      112 HIV-infected infants between six and 18 months of age. Item selection for the
      IGMST was based on the Gross Motor scale of the Bayley Scales of Infant
      Development (BSID)-III. Content validity was assessed by a panel of experts using
      a nominal group technique (NGT; agreement >80%). Concurrent validity (n=60) of
      the IGMST was carried out against the BSID-III, and agreement was excellent
      (K=0.85). The diagnostic properties of the IGMST were evaluated and revealed:
      sensitivity 97.4%, specificity 85.7%, positive predictive value (PPV) 92.7%, and
      negative predictive value (NPV) 94.7%. Reliability testing (n=30) revealed inter
      rater reliability as: r=1, test-retest reliability: r=0.98 and intra-rater
      reliability: r=0.98. The results indicate that the statistical properties of the
      IGMST are excellent, and the tool is suitable for use within the paediatric HIV
      setting.

PMID- 21732899
TI  - Use of routine data collected by the prevention of mother-to-child transmission
      program for HIV surveillance among pregnant women in Rwanda: opportunities and
      limitations.
AB  - To compare HIV prevalence measured by antenatal clinics (ANC) sentinel
      surveillance and by the prevention of mother-to-child transmission (PMTCT)
      program in Rwanda. We compared HIV prevalence from anonymous testing performed
      under ANC surveillance, and that measured from voluntary counselling and testing
      performed under the PMTCT program, in a random sample of the same population of
      pregnant women attending for their first antenatal visit at 29 ANC surveillance
      sites with a PMTCT program in 2007 in Rwanda. All of the 13,318 pregnant women
      recruited in the ANC surveillance accepted to participate in the PMTCT program.
      HIV prevalence measured by sentinel surveillance was 4.35% whereas that measured
      for 1873 pregnant women (out of the total sentinel population) by the PMTCT
      program was 3.49% (p=0.07). For 3% of the PMTCT population, HIV test results were
      missing from the counselling logbook versus 0.3% in the ANC laboratory logbooks.
      For 10 pregnant women, HIV test results were divergent between the PMTCT and the
      ANC laboratory logbooks. After missing data and errors were corrected, HIV
      prevalence results from PMTCT was 3.27% (significantly different from ANC
      surveillance: p =0.03). High uptake of PMTCT program among pregnant women was
      observed in Rwanda in 2007. HIV prevalence measured by the ANC surveillance and
      PMTCT program were significantly different. Poor performance in HIV testing
      practices and PMTCT/laboratories data management could explain this difference.
      Improvement in HIV testing practices and in PMTCT/laboratory data management are
      needed in order to use PMTCT data for HIV surveillance and to ensure good
      performance of all the package of care provided by the PMTCT program.

PMID- 21732900
TI  - Operating characteristics of carbohydrate-deficient transferrin (CDT) for
      identifying unhealthy alcohol use in adults with HIV infection.
AB  - Unhealthy alcohol use (the spectrum of risky use through dependence) is common in
      HIV-infected persons, yet it can interfere with HIV medication adherence, may
      lower CD4 cell count, and can cause hepatic injury. Carbohydrate-deficient
      transferrin (CDT), often measured as %CDT, can detect heavy drinking but whether
      it does in people with HIV is not well established. We evaluated the operating
      characteristics of %CDT in HIV-infected adults using cross-sectional data from
      300 HIV-infected adults with current or past alcohol problems. Past 30-day
      alcohol consumption was determined using the Timeline Followback (TLFB), a
      validated structured recall questionnaire, as the reference standard. Sensitivity
      and specificity of %CDT (at manufacturer's cut-off point of 2.6%) for detecting
      both "at-risk" (>=4 drinks in a day or >7 drinks per week for women, >=5 drinks
      in a day or >14 per week for men) and "heavy" drinking (>=4 drinks in a day for
      women, >=5 drinks in a day for men on at least seven days) were calculated.
      Receiver operating characteristic (ROC) curves were estimated to summarize the
      diagnostic ability of %CDT for distinguishing "at risk" and "heavy" levels of
      drinking. Exploratory analyses that stratified by gender and viral hepatitis
      infection were performed. Of 300 subjects, 103 reported current consumption at
      "at-risk" amounts, and 47 reported "heavy" amounts. For "at-risk" drinking,
      sensitivity of %CDT was 28% (95% confidence interval (CI) 19%, 37%), specificity
      90% (95% CI 86%, 94%); area under the ROC curve (AUC) was 0.59. For "heavy"
      drinking, sensitivity was 36% (95% CI 22%, 50%), specificity 88% (95% CI 84%,
      92%); AUC was 0.60. Sensitivity appeared lower among women and those with viral
      hepatitis; specificity was similar across subgroups. Among HIV-infected adults,
      %CDT testing yielded good specificity, but poor sensitivity for detecting "at
      risk" and "heavy" alcohol consumption, limiting its clinical utility for
      detecting unhealthy alcohol use in this population.

PMID- 21732901
TI  - Acceptability of circumcision as a means of HIV prevention among men who have sex
      with men in China.
AB  - Conclusive evidence-based research has shown that circumcision reduces the risk
      of HIV transmission via heterosexual intercourse, whilst ongoing studies are
      investigating similar effects via homosexual transmissions and the results are
      equivocal. Few acceptability studies regarding circumcision were conducted among
      men who have sex with men (MSM). In this cross-sectional study, a total of 307
      MSM were recruited by snowball sampling and were interviewed anonymously by some
      peer field workers in Yangzhou, China. Amongst all uncircumcised participants
      (93.4% of all participants were uncircumcised), the willingness to be circumcised
      increased from 8.1% to 30.7%, before and after the participants were briefed
      about a hypothetical potential benefit of a 50% risk reduction of circumcision in
      preventing HIV transmission among MSM. In the multivariate analysis, perception
      of overly long foreskin (odds ratio [OR] = 6.04), unprotected sexual intercourse
      with male regular sex partners in the last six months (OR = 2.04), and seeing no
      chance for contracting HIV in the next 12 months (OR = 0.54) were significantly
      associated with conditional willingness for circumcision. Adjusting for these
      variables, other significant factors were identified by multiple logistic
      regression analysis, including number of perceived disadvantages for having
      overly long foreskin (adjusted OR = 2.60), variables that were derived from the
      Theory of Planned Behaviors (TPB), and having some circumcised MSM peers
      (adjusted OR = 0.45-4.38). Some risk compensation behaviors however, may be
      practiced by 15.9% of the MSM who were willing to undergo circumcision. The
      acceptability would increase slightly with the effect size of circumcision in
      protecting MSM from HIV transmission via homosexual intercourse. However, it was
      only around 30%, even if circumcision could result in a large (50%) risk
      reduction in HIV transmission among MSM. If future studies can establish efficacy
      of circumcision, relevant promotion programs need to guard against risk
      compensation, though the magnitude of risk compensation may be moderate.

PMID- 21732902
TI  - Acceptability of male circumcision for prevention of HIV infection among men and
      women in Uganda.
AB  - In the last decade, three randomized controlled trials in Kenya, South Africa,
      and Uganda have shown that medical male circumcision (MMC) reduces the sexual
      transmission of HIV from women to men. Objectives of this assessment were to
      measure acceptability of adult MMC and circumcision of children to inform
      policies regarding whether and how to promote MMC as an HIV prevention strategy.
      This mixed-method study, conducted across four Ugandan districts, included a two
      stage household survey of 833 adult males and 842 adult females, focus group
      discussions, and a health provider survey.   Respondents' acceptability of MMC
      was positive and substantial after being informed about the results of recent
      randomized trials. In uncircumcised men, between 40% and 62% across the districts
      would consider getting circumcised. Across the four districts between 60% and 86%
      of fathers and 49% and 95% of mothers were supportive of MMC for sons. Widespread
      support exists among men and women in this study for promoting MMC as part of
      Uganda's current 'ABC + ' HIV prevention strategy.

PMID- 21732903
TI  - Pharmacoeconomic aspects of poor adherence: can better adherence reduce
      healthcare costs?
AB  - BACKGROUND: Poor adherence to medical treatment is one of the main reasons why
      patients do not achieve the full benefits of their therapy. It also has a
      substantial financial weight in terms of money wasted for unused medication and
      increased healthcare costs including hospitalization due to clinical
      complications. OBJECTIVE: To provide an overview and examples of the financial
      and economic consequences of poor adherence to treatment, techniques and devices
      for monitoring adherence and interventions for improvement of treatment
      adherence. RESULTS: New electronic devices with monitoring features may help to
      objectively monitor patients' adherence to a treatment regimen that can help a
      healthcare professional determine how to intervene to improve adherence and
      subsequent clinical outcome. Interventions that aim to enhance adherence may
      confer cost-effectiveness benefits in some indications and settings. The nature
      of the intervention(s) used depends on a range of factors, including patient
      preference, therapy area and cost of the intervention. However, there is a
      pressing need for rigorous trials, as current studies often have major flaws in
      the economic methodology, especially in terms of incremental analysis and
      sensitivity analysis. LIMITATIONS: This review has focused on a limited number of
      therapeutic areas as coverage of a more extensive range of diseases may be beyond
      the scope of such a summary. Nevertheless, the examples are representative of the
      challenges encountered in many other diseases. CONCLUSIONS: The clinical and
      economic consequences of non-adherence and interventions to improve compliance
      reflect the nature and severity of non-adherence, as well as the pathophysiology
      and severity of the disease. Interventions that aim to enhance adherence may
      confer cost-effectiveness benefits in some indications and settings, and good
      adherence can help payers and providers contain costs by extracting maximum value
      from their investment in therapies.

PMID- 21732904
TI  - Management of vaccinations in Italy: a national survey after healthcare
      regionalization.
AB  - OBJECTIVES: The main aim of this study was to describe the effects of regional
      organization and performance in managing vaccinations, in the light of the
      institutional devolution recently introduced in Italy. METHODS: We analysed (1)
      the general organization of regions for vaccination programmes, (2) the
      management of four vaccination programmes (combined measles-rubella-parotitis,
      varicella for children, influenza, and pneumococcal 23-valent for adults). First,
      we conducted preliminary face-to-face interviews with 16 regional managers of the
      infective disease prevention departments. Subsequently, we sent them a
      standardized questionnaire to obtain comparable information on general
      organization and on the four specific vaccination programmes considered. In all,
      14 regions were eventually included. RESULTS: The survey showed a widespread lack
      of regional staff involved in the management of vaccinations and a geographical
      variation in the availability of computerized data collection. We recorded poor
      coverage for varicella and pneumococcal 23-valent vaccinations compared to MRP
      and influenza. Prices of the four vaccines varied widely among regions, with only
      a weak correlation between prices and volumes. LIMITATIONS AND CONCLUSIONS: The
      major limitation of the survey was the lack of information available at regional
      level. The piecemeal diffusion of computerized systems and the widespread lack of
      sufficient staff should mainly explain this. Economic incentives could be offered
      to regions that achieve national targets. Such incentives should encourage
      collaboration between central and regional authorities consistent with
      institutional trends in regional devolution.

PMID- 21732905
TI  - Exogenous hCG activity, but not endogenous LH activity, is positively associated
      with live birth rates in anovulatory infertility.
AB  - OBJECTIVE: To evaluate, retrospectively, the roles of endogenous and exogenous
      luteinising hormone (LH) activity on live birth rate in ovulation induction
      cycles. METHODS: Associations between LH activity at baseline, end of stimulation
      and live birth rate were analysed in relation to patient characteristics,
      baseline and end of stimulation variables in WHO group II anovulatory women (n =
      155) stimulated with recombinant follicle-stimulating hormone (rFSH) or highly
      purified human menopausal gonadotrophin (HP-hMG). HP-hMG provides FSH and
      exogenous LH activity mainly in the form of human chorionic gonadotrophin (hCG).
      RESULTS: Serum LH concentrations at baseline or end of stimulation were not
      predictive of live birth rate in the rFSH group (n = 79) or HP-hMG group (n =
      76). Serum hCG concentration at end of stimulation was a significant positive
      predictor in HP-hMG-treated women. Other variables were not independently
      predictive of live birth in either of the groups, except for a negative
      association between serum FSH concentrations at the start of stimulation and live
      birth in the rFSH-treated group. CONCLUSIONS: Endogenous LH concentrations are
      not predictive of live birth in anovulatory WHO group II patients undergoing
      ovulation induction with rFSH or HP-hMG. On the other hand, exogenous hCG
      activity during HP-hMG stimulation is positively associated with treatment
      outcome.

PMID- 21732906
TI  - Associations of positive and negative life changes with well-being in young and
      middle-aged adult cancer survivors.
AB  - Both positive and negative changes are commonly reported by cancer survivors, and
      both may impact quality of life. Yet few studies have directly compared the
      associations of positive and negative changes across multiple life domains with
      multiple aspects of well-being. This study examined positive and negative changes
      and their conjoint relation to a range of well-being indices. We used
      correlational and regression analyses of data from 237 young to middle aged (X =
      45.3 years) cancer survivors, several years after treatment. Measures included
      demographic and medical variables, medical post-cancer positive and negative
      changes on multiple life domains, and a range of positive and negative adjustment
      indices. Demographic factors, especially income, related to both positive and
      negative outcomes. On average, participants reported no change on most life
      domains, although modest amounts of both positive and negative changes were
      reported. Negative change, rather than positive change, was closely associated
      with cancer survivors' adjustment. Detailed measurement of both positive and
      negative changes - as well as lack of change - is important to advance
      understanding of cancer's impact on survivors.

PMID- 21732907
TI  - Chemical constituents of Jordanian propolis.
AB  - Seventeen compounds, including a new lanostane triterpenoid, 24(Z)-1beta-3beta
      dihydroxyeupha-7,24-dien-26-oic acid, have been isolated from the methanolic
      extracts of two samples of Jordanian propolis collected from two different places
      with different dominant flora. The structures of the isolated compounds were
      elucidated by spectral methods including IR, UV, MS and 1- and 2-D NMR.

PMID- 21732908
TI  - Isolation, characterisation and cytotoxicity study of arjunolic acid from
      Terminalia arjuna.
AB  - Arjunolic acid (AA), a triterpenoid, was isolated from the ethyl acetate and
      methanol extracts of Terminalia arjuna core wood. The purity of AA was analysed
      by its melting point, FT-IR and NMR spectroscopy analyses. In vitro cytotoxicity
      was assessed using Ehrlich ascites carcinoma (EAC) and Dalton's lymphoma (DAL)
      cell lines by incubating with different concentrations of AA. The cancer cell
      death percentage at 100 ug concentrations of AA ranged between 66% and 70% on the
      DAL and EAC cell lines, respectively. This infers that AA causes considerable
      membrane damage to cancer cells.

PMID- 21732909
TI  - Water and urea permeation pathways of the human excitatory amino acid transporter
      EAAT1.
AB  - Glutamate transport is coupled to the co-transport of 3 Na(+) and 1 H(+) followed
      by the counter-transport of 1 K(+). In addition, glutamate and Na(+) binding to
      glutamate transporters generates an uncoupled anion conductance. The human glial
      glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows
      significant passive and active water transport, which suggests that water
      permeation through glutamate transporters may play an important role in glial
      cell homoeostasis. Urea also permeates EAAT1 and has been used to characterize
      the permeation properties of the transporter. We have previously identified a
      series of mutations that differentially affect either the glutamate transport
      process or the substrate-activated channel function of EAAT1. The water and urea
      permeation properties of wild-type EAAT1 and two mutant transporters were
      measured to identify which permeation pathway facilitates the movement of these
      molecules. We demonstrate that there is a significant rate of L-glutamate
      stimulated passive and active water transport. Both the passive and active L
      glutamate-stimulated water transport is most closely associated with the
      glutamate transport process. In contrast, L-glutamate-stimulated [(14)C]urea
      permeation is associated with the anion channel of the transporter. However,
      there is also likely to be a transporter-specific, but glutamate independent,
      flux of water via the anion channel.

PMID- 21732910
TI  - Intraflagellar transport proteins in ciliogenesis of photoreceptor cells.
AB  - BACKGROUND INFORMATION: The assembly and maintenance of cilia depend on IFT
      (intraflagellar transport) mediated by molecular motors and their interplay with
      IFT proteins. Here, we have analysed the involvement of IFT proteins in the
      ciliogenesis of mammalian photoreceptor cilia. RESULTS: Electron microscopy
      revealed that ciliogenesis in mouse photoreceptor cells follows an intracellular
      ciliogenesis pathway, divided into six distinct stages. The first stages are
      characterized by electron-dense centriolar satellites and a ciliary vesicle,
      whereas the formations of the ciliary shaft and the light-sensitive outer segment
      discs are features of the later stages. IFT proteins were associated with ciliary
      apparatus during all stages of photoreceptor cell development. CONCLUSIONS: Our
      data conclusively provide evidence for the participation of IFT proteins in
      photoreceptor cell ciliogenesis, including the formation of the ciliary vesicle
      and the elongation of the primary cilium. In advanced stages of ciliogenesis the
      ciliary localization of IFT proteins indicates a role in IFT as is seen in mature
      cilia. A prominent accumulation of IFT proteins in the periciliary cytoplasm at
      the base of the cilia in these stages most probably resembles a reserve pool of
      IFT molecules for further delivery into the growing ciliary shaft and their
      subsequent function in IFT. Nevertheless, the cytoplasmic localization of IFT
      proteins in the absence of a ciliary shaft in early stages of ciliogenesis may
      indicate roles of IFT proteins beyond their well-established function for IFT in
      mature cilia and flagella.

PMID- 21732911
TI  - Characterization of a novel angiogenic model based on stable, fluorescently
      labelled endothelial cell lines amenable to scale-up for high content screening.
AB  - BACKGROUND: Blood vessel formation is important for many physiological and
      pathological processes and is therefore a critical target for drug development.
      Inhibiting angiogenesis to starve a tumour or promoting 'normalization' of tumour
      vasculature in order to facilitate delivery of anticancer drugs are both areas of
      active research. Recapitulation of vessel formation by human cells in vitro
      allows the investigation of cell-cell and cell-matrix interactions in a
      controlled environment and is therefore a crucial step in developing HCS (high
      content screening) and HTS (high throughput screening) assays to search for
      modulators of blood vessel formation. HUVECs (human umbilical-vein endothelial
      cells) exemplify primary cells used in angiogenesis assays. However, primary
      cells have significant limitations that include phenotypic decay and/or
      senescence by six to eight passages in culture, making stable integration of
      fluorescent markers and large-scale expansion for HTS problematic. To overcome
      these limitations for HTS, we developed a novel angiogenic model system that
      employs stable fluorescent endothelial cell lines based on immortalized HMECs
      (human microvascular endothelial cell). We then evaluated HMEC cultures, both
      alone and co-cultured with an EMC (epicardial mesothelial cell) line that
      contributes vascular smooth muscle cells, to determine the suitability for HTS or
      HCS. RESULTS: The endothelial and epicardial lines were engineered to express a
      panel of nuclear- and cytoplasm-localized fluorescent proteins to be mixed and
      matched to suit particular experimental goals. HMECs retained their angiogenic
      potential and stably expressed fluorescent proteins for at least 13 passages
      after transduction. Within 8 h after plating on Matrigel, the cells migrated and
      coalesced into networks of vessel-like structures. If co-cultured with EMCs, the
      branches formed cylindrical-shaped structures of HMECs surrounded by EMC
      derivatives reminiscent of vessels. Network formation measurements revealed
      responsiveness to media composition and control compounds. CONCLUSIONS: HMEC
      based lines retain most of the angiogenic features of primary endothelial cells
      and yet possess long-term stability and ease of culture, making them intriguing
      candidates for large-scale primary HCS and HTS (of ~10000-1000000 molecules).
      Furthermore, inclusion of EMCs demonstrates the feasibility of using epicardial
      derived cells, which normally contribute to smooth muscle, to model large vessel
      formation. In summary, the immortalized fluorescent HMEC and EMC lines and
      straightforward culture conditions will enable assay development for HCS of
      angiogenesis.

PMID- 21732912
TI  - MAL, but not MAL2, expression promotes the formation of cholesterol-dependent
      membrane domains that recruit apical proteins.
AB  - Our recent studies have been aimed at understanding the mechanisms regulating
      apical protein sorting in polarized epithelial cells. In particular, we have been
      investigating how lipid rafts serve to sort apical proteins in the biosynthetic
      pathway. The recent findings that lipid domains are too small or transient to
      host apically destined cargo have led to newer versions of the hypothesis that
      invoke proteins required for lipid domain coalescence and stabilization. MAL
      (myelin and lymphocyte protein) and its highly conserved family member, MAL2,
      have emerged as possible regulators of this process in the direct and indirect
      apical trafficking pathways respectively. To test this possibility, we took a
      biochemical approach. We determined that MAL, but not MAL2, self-associates,
      forms higher-order cholesterol-dependent complexes with apical proteins and
      promotes the formation of detergent-resistant membranes that recruit apical
      proteins. Such biochemical properties are consistent with a role for MAL in raft
      coalescence and stabilization. These findings also support a model whereby
      hydrophobic mismatch between the long membrane-spanning helices of MAL and the
      short-acyl-chain phospholipids in the Golgi drive formation of lipid domains rich
      in raft components that are characterized by a thicker hydrophobic core to
      alleviate mismatch.

PMID- 21732913
TI  - Interaction between the SH3 domain of Src family kinases and the proline-rich
      motif of HTLV-1 p13: a novel mechanism underlying delivery of Src family kinases
      to mitochondria.
AB  - The association of the SH3 (Src homology 3) domain of SFKs (Src family kinases)
      with protein partners bearing proline-rich motifs has been implicated in the
      regulation of SFK activity, and has been described as a possible mechanism of
      relocalization of SFKs to subcellular compartments. We demonstrate in the present
      study for the first time that p13, an accessory protein encoded by the HTLV-1
      (human T-cell leukaemia virus type 1), binds the SH3 domain of SFKs via its C
      terminal proline-rich motif, forming a stable heterodimer that translocates to
      mitochondria by virtue of its N-terminal mitochondrial localization signal. As a
      result, the activity of SFKs is dramatically enhanced, with a subsequent increase
      in mitochondrial tyrosine phosphorylation, and the recognized ability of p13 to
      insert itself into the inner mitochondrial membrane and to perturb the
      mitochondrial membrane potential is abolished. Overall, the present study, in
      addition to confirming that the catalytic activity of SFKs is modulated by
      interactors of their SH3 domain, leads us to hypothesize a general mechanism by
      which proteins bearing a proline-rich motif and a mitochondrial localization
      signal at the same time may act as carriers of SFKs into mitochondria, thus
      contributing to the regulation of mitochondrial functions under various
      pathophysiological conditions.

PMID- 21732914
TI  - Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate
      sulfurtransferase to produce hydrogen sulfide.
AB  - H2S (hydrogen sulfide) has recently been recognized as a signalling molecule as
      well as a cytoprotectant. We recently demonstrated that 3MST (3-mercaptopyruvate
      sulfurtransferase) produces H2S from 3MP (3-mercaptopyruvate). Although a
      reducing substance is required for an intermediate persulfide at the active site
      of 3MST to release H2S, the substance has not been identified. In the present
      study we show that Trx (thioredoxin) and DHLA (dihydrolipoic acid) associate with
      3MST to release H2S. Other reducing substances, such as NADPH, NADH, GSH,
      cysteine and CoA, did not have any effect on the reaction. We also show that 3MST
      produces H2S from thiosulfate. The present study provides a new insight into a
      mechanism for the production of H2S by 3MST.

PMID- 21732915
TI  - Novel NADPH-cysteine covalent adduct found in the active site of an aldehyde
      dehydrogenase.
AB  - PaBADH (Pseudomonas aeruginosa betaine aldehyde dehydrogenase) catalyses the
      irreversible NAD(P)+-dependent oxidation of betaine aldehyde to its corresponding
      acid, the osmoprotector glycine betaine. This reaction is involved in the
      catabolism of choline and in the response of this important pathogen to the
      osmotic and oxidative stresses prevalent in infection sites. The crystal
      structure of PaBADH in complex with NADPH showed a novel covalent adduct between
      the C2N of the pyridine ring and the sulfur atom of the catalytic cysteine
      residue, Cys286. This kind of adduct has not been reported previously either for
      a cysteine residue or for a low-molecular-mass thiol. The Michael addition of the
      cysteine thiolate in the 'resting' conformation to the double bond of the
      alpha,beta-unsaturated nicotinamide is facilitated by the particular conformation
      of NADPH in the active site of PaBADH (also observed in the crystal structure of
      the Cys286Ala mutant) and by an ordered water molecule hydrogen bonded to the
      carboxamide group. Reversible formation of NAD(P)H-Cys286 adducts in solution
      causes reversible enzyme inactivation as well as the loss of Cys286 reactivity
      towards thiol-specific reagents. This novel covalent modification may provide a
      physiologically relevant regulatory mechanism of the irreversible PaBADH
      catalysed reaction, preventing deleterious decreases in the intracellular
      NAD(P)+/NAD(P)H ratios.

PMID- 21732916
TI  - A new HLA-B*15 allele, B*15:220, found in three individuals sharing the HLA
      A*66:01, HLA-C*12:03 and HLADRB1*07:01 alleles.
AB  - The new allele HLA-B*15:220 is associated with a conserved haplotype.

PMID- 21732917
TI  - Characterization of 236 novel alleles at the HLA-A, -B, -C, -DRB1, -DQB1 and 
      DPB1 loci from China Marrow Donor Program.
AB  - Two hundred and thirty-six novel human leukocyte antigen (HLA) alleles are
      described from volunteer donors of the China Marrow Donor Program: 71 HLA-A
      alleles, 79 HLA-B alleles, 43 HLA-C, 16 HLA-DRB1 alleles, 26 HLA-DQB1 and 1 HLA
      DPB1. Two hundred and thirteen (90.3%) of the 236 novel alleles are single
      nucleotide substitution variants when compared with their most homologous allele.
      Seventy-eight of these single nucleotide variants are silent substitutions. The
      remaining novel alleles differ from their most similar allele by two to four
      nucleotide substitutions. Some of the novel alleles encode amino acid changes at
      positions not previously reported to be polymorphic, such as codons 57, 62, 67,
      41 and 52 in HLA-A alleles; codons 133, 156, 201 and 215 in HLA-B alleles; codons
      74, 208 and 225 in HLA-C; codons 25, 32 and 72 in HLA-DRB1; codons 20, 39 and 77
      in HLA-DQB1.

PMID- 21732918
TI  - Characterization of new HLA-A and -B alleles from Kazakhstan.
AB  - Eight novel alleles, two HLA-A and six HLA-B, are described in Kazakh
      individuals.

PMID- 21732919
TI  - Normal muscle MRI does not preclude increased connective tissue in muscle of
      recessive myotonia congenita.

PMID- 21732921
TI  - Serum adiponectin after ischemic stroke.

PMID- 21732923
TI  - Timing of do-not-resuscitate orders for hospitalized older adults who require a
      surrogate decision-maker.
AB  - OBJECTIVES: To examine the frequency of surrogate decisions for in-hospital do
      not-resuscitate (DNR) orders and the timing of DNR order entry for surrogate
      decisions. DESIGN: Retrospective cohort study. SETTING: Large, urban, public
      hospital. PARTICIPANTS: Hospitalized adults aged 65 and older over a 3-year
      period (1/1/2004-12/31/2006) with a DNR order during their hospital stay.
      MEASUREMENTS: Electronic chart review provided data on frequency of surrogate
      decisions, patient demographic and clinical characteristics, and timing of DNR
      orders. RESULTS: Of 668 patients, the ordering physician indicated that the DNR
      decision was made with the patient in 191 cases (28.9%), the surrogate in 389
      (58.2%), and both in 88 (13.2%). Patients who required a surrogate were more
      likely to be in the intensive care unit (62.2% vs 39.8%, P<.001) but did not
      differ according to demographic characteristics. By hospital Day 3, 77.6% of
      patient decisions, 61.9% of surrogate decisions, and 58.0% of shared decisions
      had been made. In multivariable models, the number of days from admission to DNR
      order was higher for surrogate (odds ratio (OR)=1.97, P<.001) and shared
      decisions (OR=1.48, P=.009) than for patient decisions. The adjusted hazard ratio
      for hospital death was higher for patients with surrogate than patient decisions
      (2.61, 95% confidence interval (CI)=1.56-4.36). Patients whose DNR orders were
      written on Day 6 or later were twice as likely to die in the hospital (OR=2.20,
      95% CI=1.45-3.36) than patients with earlier DNR orders. CONCLUSION: For patients
      who have a DNR order entered during their hospital stay, order entry occurs later
      when a surrogate is involved. Surrogate decision-making may take longer because
      of the greater ethical, emotional, or communication complexity of making
      decisions with surrogates than with patients.

PMID- 21732924
TI  - Effect of mental disorders on diagnosis, treatment, and survival of older adults
      with colon cancer.
AB  - OBJECTIVES: To evaluate the extent to which preexisting mental disorders
      influence diagnosis, treatment, and survival in older adults with colon cancer.
      DESIGN: Retrospective cohort study. SETTING: The Surveillance, Epidemiology and
      End Results (SEER)-Medicare linked database. PARTICIPANTS: Eighty thousand six
      hundred seventy participants, aged 67 and older with a diagnosis of colon cancer.
      MEASUREMENTS: The association between the presence of a preexisting mental
      disorder and the stage of colon cancer at diagnosis, receipt of cancer treatment,
      and overall and colon cancer-specific mortality were assessed using Cox
      proportional hazards regression and logistic regression. RESULTS: Participants
      with mental disorders were more likely to have been diagnosed with colon cancer
      at autopsy (4.4% vs 1.1%; P<.001) and at an unknown stage of cancer (14.6% vs
      6.2%; P<.001); to have received no surgery, chemotherapy, or radiation therapy
      (adjusted risk ratio (ARR)=2.09, 95% confidence interval (CI)=1.86-2.35); and to
      have received no chemotherapy for Stage 3 cancer (ARR=1.63, 95% CI=1.49-1.79).
      The rate of overall mortality (hazard ratio (HR)=1.33, 95% CI=1.31-1.36) and
      colon cancer-specific mortality (HR=1.23, 95% CI=1.19-1.27) was substantially
      higher in participants with a preexisting mental disorder than in their
      counterparts. All of these associations were particularly pronounced in
      participants with psychotic disorders and those with dementia. CONCLUSION: Public
      health initiatives are needed to improve colon cancer detection and treatment in
      older adults with mental disorders.

PMID- 21732925
TI  - Predictive cross-validation for the choice of linear mixed-effects models with
      application to data from the Swiss HIV Cohort Study.
AB  - Model choice in linear mixed-effects models for longitudinal data is a
      challenging task. Apart from the selection of covariates, also the choice of the
      random effects and the residual correlation structure should be possible.
      Application of classical model choice criteria such as Akaike information
      criterion (AIC) or Bayesian information criterion is not obvious, and many
      versions do exist. In this article, a predictive cross-validation approach to
      model choice is proposed based on the logarithmic and the continuous ranked
      probability score. In contrast to full cross-validation, the model has to be
      fitted only once, which enables fast computations, even for large data sets.
      Relationships to the recently proposed conditional AIC are discussed. The
      methodology is applied to search for the best model to predict the course of CD4+
      counts using data obtained from the Swiss HIV Cohort Study.

PMID- 21732926
TI  - A powerful and robust test statistic for randomization inference in group
      randomized trials with matched pairs of groups.
AB  - For group-randomized trials, randomization inference based on rank statistics
      provides robust, exact inference against nonnormal distributions. However, in a
      matched-pair design, the currently available rank-based statistics lose
      significant power compared to normal linear mixed model (LMM) test statistics
      when the LMM is true. In this article, we investigate and develop an optimal test
      statistic over all statistics in the form of the weighted sum of signed Mann
      Whitney-Wilcoxon statistics under certain assumptions. This test is almost as
      powerful as the LMM even when the LMM is true, but it is much more powerful for
      heavy tailed distributions. A simulation study is conducted to examine the power.

PMID- 21732927
TI  - Senicapoc trial results support the existence of different sub-phenotypes of
      sickle cell disease with possible drug-induced phenotypic shifts.

PMID- 21732928
TI  - A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins
      (Combotox) in adult patients with refractory B-lineage acute lymphoblastic
      leukaemia.
AB  - Novel agents are needed for patients with refractory and relapsed acute
      lymphoblastic leukaemia (ALL). Combotox is a 1:1 mixture of two immunotoxins
      (ITs), prepared by coupling deglycosylated ricin A chain (dgRTA) to monoclonal
      antibodies directed against CD22 (RFB4-dgRTA) and CD19 (HD37-dgRTA). Pre-clinical
      data demonstrated that Combotox was effective in killing both pre-B-ALL cell
      lines and cells from patients with pre-B ALL. A clinical study of paediatric
      patients in which 3 of 17 patients with ALL experienced complete remission,
      supported the preclinical work and motivated this study. This study was a Phase
      I, dose-escalation trial using Combotox in adults with refractory or relapsed B
      lineage-ALL. A cycle consisted of three doses, with one dose given every other
      day. Dose levels were 3, 5, 6, 7 and 8 mg/m(2) per dose. Seventeen patients, aged
      19-72 years, were enrolled in this multi-institution study. The maximum tolerated
      dose was 7 mg/m(2) /dose (21 mg/m(2) /cycle) and vascular leak syndrome was the
      dose-limiting toxicity. Two patients developed reversible grade 3 elevations in
      liver function tests. One patient achieved partial remission and proceeded to
      allogeneic stem cell transplantation. All patients with peripheral blasts
      experienced decreased blast counts following the administration of Combotox.
      Thus, Combotox can be safely administered to adults with refractory leukaemia.

PMID- 21732929
TI  - Molecular analysis of globin gene expression in different thalassaemia disorders:
      individual variation of beta(E) pre-mRNA splicing determine disease severity.
AB  - Thalassaemia is characterized by the reduced or absent production of globins in
      the haemoglobin molecule leading to imbalanced alpha-globin/non alpha-globin
      chains. HbE, the result of a G to A mutation in codon 26 of the HBB (beta-globin)
      gene, activates a cryptic 5' splice site in codon 25 leading to a reduction of
      correctly spliced beta(E) -globin (HBB:c.79G>A) mRNA and consequently beta(+) 
      thalassaemia. A wide range of clinical severities in bothalpha- and beta
      thalassaemia syndromes, from nearly asymptomatic to transfusion-dependent, has
      been observed. The correlation between clinical heterogeneity in various
      genotypes of thalassaemia and the levels of globin gene expression and beta(E) 
      globin pre-mRNA splicing were examined using multiplex quantitative real-time
      reverse transcription polymerase chain reaction (RT-qPCR) and allele-specific RT
      qPCR. The alpha-globin/non alpha-globin mRNA ratio was demonstrated to be a good
      indicator for disease severity among different thalassaemia disorders. However,
      the alpha-globin/non alpha-globin mRNA ratio ranged widely in beta
      thalassaemia/HbE patients, with no significant difference between mild and severe
      phenotypes. Interestingly, the correctly to aberrantly spliced beta(E) -globin
      mRNA ratio in 30% of mild beta-thalassaemia/HbE patients was higher than that of
      the severe patients. The splicing process of beta(E) -globin pre-mRNA differs
      among beta-thalassaemia/HbE patients and serves as one of the modifying factors
      for disease severity.

PMID- 21732930
TI  - Managing multiple myeloma: the emerging role of novel therapies and adapting
      combination treatment for higher risk settings.
AB  - Novel therapies have transformed the treatment paradigm for multiple myeloma with
      significant improvements in survival now seen in both younger and older patients.
      Nonetheless, the disease is heterogeneous and high-risk patients in particular
      continue to have poor outcome. Moreover, the disease remains incurable. Efforts
      to refine risk stratification and disease characteristics continue with the use
      of cytogenetics, enhanced imaging techniques and other new technologies, such as
      genomics. The integration of novel therapies into induction therapy,
      consolidation and maintenance continues to evolve, and the appropriate use of
      combination strategies including proteasome inhibition and immunomodulatory
      treatment is emerging as a platform with application across the disease spectrum.
      Despite these advances, resistance to novel agents occurs and so the
      identification of new targets and the recognition of clonal heterogeneity are
      especially important as improvements to current treatment strategies are
      developed, with the goal of further improving patient outcome. 

PMID- 21732931
TI  - The impact of ignoring multiple membership data structures in multilevel models.
AB  - This study compared the use of the conventional multilevel model (MM) with that
      of the multiple membership multilevel model (MMMM) for handling multiple
      membership data structures. Multiple membership data structures are commonly
      encountered in longitudinal educational data sets in which, for example, mobile
      students are members of more than one higher-level unit (e.g., school). While the
      conventional MM requires the user either to delete mobile students' data or to
      ignore prior schools attended, MMMM permits inclusion of mobile students' data
      and models the effect of all schools attended on student outcomes. The simulation
      study identified underestimation of the school-level predictor coefficient, as
      well as underestimation of the level-two variance component with corresponding
      overestimation of the level-one variance when multiple membership data structures
      were ignored. Results are discussed along with limitations and ideas for future
      MMMM methodological research as well as implications for applied researchers.

PMID- 21732932
TI  - Conceptual relevance of new-onset epilepsy.
AB  - The definitions of "first seizure" and "new-onset epilepsy" are arbitrary and
      rather simple for use to describe the beginning of a complex brain disease in
      which seizures are only one symptom. A diligent study of early stages in epilepsy
      including detailed clinical information, psychiatric comorbidities, sophisticated
      advanced neuroimaging, and timely functional brain tests may provide a better
      understanding of epileptogenesis. The goal will be to understand the process of
      evolution to chronic epilepsy and eventually to prevent refractory epilepsy.

PMID- 21732933
TI  - Neuroimaging predictors of AED resistance in new-onset epilepsies.
AB  - The best prognostic factors in early-onset epilepsies are the response to the
      first antiepileptic drug (AED) trial, age at seizure onset, number of seizures
      prior to treatment, and the presence of a lesion or abnormal neurologic
      examination. However, early and adequate response to AED is most likely an
      epiphenomenon reflecting the nature of underlying epileptogenicity, which may be
      defined as a complex interaction of underlying pathology, genetics, and
      environment. Patients with the same type of epileptogenic lesion, for example,
      hippocampal sclerosis, may have a varying response to AED. Modern neuroimaging,
      in particular quantitative magnetic resonance imaging (MRI) techniques may be
      helpful to better understand this complex interaction of factors leading to
      refractoriness. Patients who respond well to AEDs have no or minor MRI
      abnormalities, and among those with underlying lesions there is an inverse
      correlation between outcome and the extent of MRI-defined neuronal damage outside
      the main lesion, which may be undetectable by visual analyses of routine MRI. The
      extent of neuronal damage appears to be related to the severity of initial
      precipitating injuries, probably interacts with genetic factors, and may progress
      over time when seizures are uncontrolled. The presence and extent of
      abnormalities detected by quantitative MRI may also be helpful to guide AED
      withdrawal in those patients who are seizure free for >2 years. Combined MRI
      measures may have potential clinical value for predicting AED response in near
      future.

PMID- 21732934
TI  - The role of magnetoencephalography in "nonlesional" epilepsy.
AB  - The surgical management of neocortical epilepsy is challenging because many
      patients are without obvious structural lesions, or lesions are small and easily
      overlooked during routine clinical interpretation of magnetic resonance imaging
      (MRI) data. Even when functional imaging data suggest focal epileptiform
      pathology, in the absence of a concordant structural lesion, invasive monitoring
      is often required to confirm that an appropriate surgical target has been
      identified. This study sought to determine the extent to which knowledge of
      magnetoencephalography (MEG) data can augment the MRI-based detection of
      structural brain lesions. MRI and whole-head MEG data were obtained from 40
      patients with neocortical epilepsy. As a result of MEG data, 29 cases were sent
      for MRI reevaluation. In seven of these cases, MEG-guided review led to
      specification of now clear, but previously unidentified, lesions. There were two
      additional cases for which follow-up high-resolution imaging did not confirm
      structural abnormalities. In patients with neocortical epilepsy, MEG is a useful
      adjunct to MRI for the identification of structural lesions.

PMID- 21732935
TI  - The methylation hypothesis: do epigenetic chromatin modifications play a role in
      epileptogenesis?
AB  - Any structural brain lesion can provoke epilepsy, although onset and progression
      of seizures as well as response to antiepileptic drug (AED) treatment remain
      difficult to predict in each patient. Tremendous work has focused on the
      development of new AED compounds with the intention to treat seizures. However,
      these efforts have not yet discovered a "magic bullet" that cures epilepsy in
      every patient or modifies disease progression. With the "methylation hypothesis"
      we propose that epigenetic mechanisms play a pivotal role in epileptogenesis in
      patients with structural lesions. "Epigenetics" is defined as information that is
      heritable during cell division other than the DNA sequence itself, that is, DNA
      methylation or histone tail modifications, which can produce lasting alterations
      in chromatin structure and gene expression. They are increasingly recognized as
      fundamental regulatory processes in central nervous system development, synaptic
      plasticity, and memory, and also play a role in neurologic disorders such as
      schizophrenia and spinal muscular atrophy. The methylation hypothesis suggests
      that seizures by themselves can induce epigenetic chromatin modifications,
      thereby aggravating the epileptogenic condition. The impact of the methylation
      hypothesis for new-onset epilepsy will be discussed. Unravelling of epigenetic
      pathomechanisms will also open new strategies to identify molecular targets for
      pharmacologic treatment in epilepsies.

PMID- 21732936
TI  - Unveiling epileptogenic lesions: the contribution of image processing.
AB  - Magnetic resonance imaging (MRI) is a pivotal component in the investigation of
      patients with any form of epilepsy because of its unmatched ability in
      visualizing structural brain pathology. The MRI signature of newly diagnosed
      epilepsy is not yet fully defined, mainly because of the lack of a cohesive
      methodology to evaluate structural changes in the early stages of the disease. By
      revealing subtle lesions that previously eluded visual inspection in patients
      with drug-resistant epilepsy, quantitative computer-assisted image analysis has
      clearly demonstrated increased sensitivity and diagnostic accuracy compared to
      conventional techniques. Therefore, the application of image processing methods
      in patients with newly diagnosed epilepsy promises to reduce the trial-error
      period in potential surgical candidates, provide solid biomarkers for monitoring
      the disease and identifying treatment responders. A clearer understanding of
      brain pathology at the early stages of the disorder will help clinicians to
      develop better criteria for identifying patients who are at risk of secondary
      brain damage and for timely intervention that achieves seizure control.

PMID- 21732937
TI  - MRI-negative epilepsy: protocols to optimize lesion detection.
AB  - Identification of the structural lesions that underlie pediatric epilepsy can be
      challenging. Careful evaluation of the gray-white matter interface is crucial,
      and necessitates multiplanar thin images of high resolution that can
      differentiate focal lesions from partial volume averaging artifacts created by
      the innate gyral configuration. Careful evaluation of the hippocampus and of the
      myelination patterns can further increase the diagnostic yield of the study.
      Magnetization transfer imaging can call attention to a lesion that is either very
      subtle or not evident on conventional sequences. Detection of cortical anomalies
      is best performed early in infancy, preferably before 6 months of age. If the
      initial magnetic resonance imaging (MRI) scan is performed between 9 and 18
      months of age and is negative, a repeat scan after 2 years of age may be
      necessary.

PMID- 21732938
TI  - Evaluation of brain connectivity: the role of magnetoencephalography.
AB  - Communication between regions of the brain, both normal interactions and
      pathologic traffic, is manifest by electromagnetic activity.
      Magnetoencephalography (MEG)--with high resolution in both the temporal and
      spatial domains, as well as a comprehensive, whole-head view--offers ready
      noninvasive access to this ongoing communication. The waveforms are amenable to a
      variety of signal processing techniques that can elucidate connectivity between
      brain areas. In conjunction with the other modalities acquired during the
      evaluation of a patient with epilepsy, MEG can provide information that is
      important for determining therapeutic strategy.

PMID- 21732939
TI  - Diffusion tensor imaging in temporal lobe epilepsy.
AB  - Although mesial temporal sclerosis (MTS) has long been recognized in association
      with temporal lobe epilepsy (TLE), there is a growing body of literature
      suggesting structural abnormalities extending beyond the temporal lobe in
      patients with TLE. Diffusion tensor imaging (DTI) is a novel imaging technique
      that provides insight into the structural integrity of cerebral white matter. DTI
      studies have demonstrated extensive bilateral white matter abnormalities in TLE
      that extend far beyond the temporal lobe, even in patients with unilateral MTS.
      The relationship between white matter abnormalities, seizures, and comorbidity in
      TLE remains unclear.

PMID- 21732940
TI  - Gender and drug effects on neuroimaging in epilepsy.
AB  - Men are different from women, and patients with epilepsy are different in many
      aspects from healthy control subjects. Quantitative or semiquantitative analysis
      of neuroimaging data depends on the comparison between either a single patient
      against a group of healthy or unaffected controls, or comparisons between groups
      of patients and controls. Matching for gender is desired, but is sometimes not
      possible, for example, in the case of nuclear medicine with women in childbearing
      age usually not being recruited as healthy controls. Antiepileptic drug treatment
      is the other major confounder for comparisons of cognitive functioning between
      patients and healthy control subjects. Whether these two covariates, gender and
      drug effects, are of interest or nuisance variables depends on the question and
      design of the neuroimaging study.

PMID- 21732941
TI  - Combining EEG and fMRI in the study of epileptic discharges.
AB  - The combining of electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) is a unique noninvasive method for investigating the brain regions
      involved at the time of epileptic discharges. The neuronal discharges taking
      place during an interictal spike or spike-wave burst result in an increase in
      metabolism and blood flow, which is reflected in the blood oxygen-level dependent
      (BOLD) signal measured by fMRI. This increase is most intense in the region
      generating the discharge but is also present in regions affected by the
      discharge. On occasion, epileptic discharges result in decreased metabolism, the
      origin of which is only partially understood. EEG-fMRI applied to focal epilepsy
      results in maxima of the BOLD signal most often concordant with other methods of
      localization and has been shown to help in localizing epileptic foci in
      nonlesional frontal lobe epilepsy. It has also demonstrated the involvement of
      the thalamus in generalized epileptic discharges. In patients with new-onset
      epilepsy it could be used to evaluate the source and extent of the brain
      structures involved during discharges and their evolution as the disease
      progresses.

PMID- 21732942
TI  - Tracking cognitive changes in new-onset epilepsy: functional imaging challenges.
AB  - Functional imaging has potential for tracking changes in cognition during the
      onset and evolution of epilepsy. Although the concept of imaging such changes
      over time is an exciting new direction, feasibility remains an open question. The
      current article outlines a case example in which functional magnetic resonance
      imaging (fMRI) and event-related potentials (ERPs) were used to monitor memory
      changes before and after selective temporal lobe resection. From this example,
      three key methodologic challenges for new-onset epilepsy are identified and
      discussed. The first challenge relates to the interpretation of results in
      regions near epileptogenic tissue. We argue that this is best addressed by
      collecting information from multiple modalities to test for convergent evidence.
      The second challenge relates to optimizing the methods for sensitivity to
      detecting changes. In this case, enhanced imaging methods and a region-of
      interest approach provide necessary focus. The third and final challenge relates
      to the practical difficulties of conducting research in new-onset epilepsy cases.
      We suggest that greater integration of imaging research within the clinical
      setting is needed.

PMID- 21732943
TI  - Language reorganization in early onset temporal lobe epilepsy.
AB  - Behavioral and functional magnetic resonance imaging (fMRI) studies have
      consistently shown abnormalities of language function or cortical organization in
      patients with well-established temporal lobe epilepsy (TLE). However, whether
      these changes are present in new-onset TLE has not been studied to date. Studying
      such changes in new-onset TLE would provide valuable insight into the timing and
      factors that affect language deficits in TLE and may unmask fundamental
      differences in brain organization in persons who have TLE and those who do not.

PMID- 21732944
TI  - Neuroimaging in epilepsy: the state of the art.
AB  - Our understanding of epileptogenesis is still limited. Knowledge is increasing
      with regard to structural and functional changes in chronic stages of epilepsy.
      At the same time, we have to appreciate that there is a significant lack of such
      information in new-onset epilepsy. The First Halifax International Epilepsy
      Conference tried to fill this gap, focusing on the contribution of advanced
      neuroimaging in early stages of epilepsy. The following article aims to
      synthesize the themes that emerged from this meeting. Participants agreed that
      (1) there is a need for a unified theory of epileptogenesis, addressing the
      interplay of functional and structural brain changes; (2) neuroimaging reveals
      widespread brain alterations in epilepsy; (3) advances in neuroimaging challenge
      the concept of "MRI-negative" (magnetic resonance imaging negative) focal
      epilepsy; (4) methodologic limitations and potential confounders must be
      considered in the translation of innovative imaging approaches to clinical
      practice; and (5) there is an urgent need for longitudinal studies that begin
      early in the disease process.

PMID- 21732945
TI  - Experimental study of ERT monitoring ability to measure solute dispersion.
AB  - This paper reports experimental measurements performed to test the ability of
      electrical resistivity tomography (ERT) imaging to provide quantitative
      information about transport parameters in porous media such as the dispersivity
      alpha, the mixing front velocity u, and the retardation factor R(f)  associated
      with the sorption or trapping of the tracers in the pore structure. The flow
      experiments are performed in a homogeneous porous column placed between two
      vertical set of electrodes. Ionic and dyed tracers are injected from the bottom
      of the porous media over its full width. Under such condition, the mixing front
      is homogeneous in the transverse direction and shows an S-shape variation in the
      flow direction. The transport parameters are inferred from the variation of the
      concentration curves and are compared with data obtained from video analysis of
      the dyed tracer front. The variations of the transport parameters obtained from
      an inversion performed by the Gauss-Newton method applied on smoothness
      constrained least-squares are studied in detail. While u and R(f)  show a
      relatively small dependence on the inversion procedure, alpha is strongly
      dependent on the choice of the inversion parameters. Comparison with the video
      observations allows for the optimization of the parameters; these parameters are
      found to be robust with respect to changes in the flow condition and conductivity
      contrast.

PMID- 21732946
TI  - The effect of smoking on the mRNA expression of MMPs and TIMP-1 in untreated
      chronic periodontitis patients: a cross-sectional study.
AB  - BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs) are important for extracellular matrix. Expression of MMPs has
      been evaluated in gingiva without studying smoking. The aim of this study was to
      explore the effect of smoking on mRNA expression of MMP-1, -3, -8, -9 and -13 and
      TIMP-1 in untreated chronic periodontitis and in periodontal health. MATERIAL AND
      METHODS: Gingival samples were harvested from 30 subjects with untreated chronic
      periodontitis (15 nonsmokers and 15 smokers) and 30 periodontally healthy
      subjects (15 nonsmokers and 15 smokers). Full-mouth plaque score, gingival index,
      bleeding on probing, probing depth and clinical attachment level were recorded.
      Total RNA was isolated, and the mRNA expression of MMPs and TIMP-1 was assessed
      by RT-PCR. RESULTS: Periodontitis groups were comparable in clinical
      measurements. Nonsmoker subjects with periodontitis had statistically
      significantly higher MMP-1, lower MMP-9 and TIMP-1 expression and higher MMP
      1/TIMP-1 ratio than smokers; and higher MMP-8 expression and MMP-8/TIMP-1 and MMP
      1/TIMP-1 ratios than healthy nonsmokers. Healthy nonsmokers had statistically
      significantly higher MMP-13 expression than healthy smokers. Smoker periodontitis
      and healthy subjects had similar expression levels of MMPs and TIMP-1 and
      MMPs/TIMP-1 ratios. There was correlation among the MMPs only for smoker
      periodontitis subjects. Expression of MMP-13 was correlated with mean clinical
      attachment level. CONCLUSION: Within its limits, this study demonstrated that
      smoking affected mRNA expression of MMPs and TIMP-1, MMPs/TIMP-1 ratios and
      relationships among MMPs in untreated chronic periodontitis and expression of
      MMPs in health. In the absence of smoking, chronic periodontitis affected
      expression of MMPs and MMPs/TIMP-1 ratios.

PMID- 21732947
TI  - Effects of induced diabetes and the administration of aminoguanidine in the
      biomechanical retention of implants: a study in rats.
AB  - BACKGROUND AND OBJECTIVE: The present study aimed to assess the effects of
      induced diabetes and the administration of aminoguanidine in the biomechanical
      retention of implants in rats. MATERIAL AND METHODS: Thirty-six rats were
      randomly divided into six groups: group 1, healthy rats (no aminoguanidine);
      group 2 and group 3, healthy rats receiving 10 and 20 mg/kg of aminoguanidine
      daily, respectively; group 4, diabetic rats (no aminoguanidine); and group 5 and
      group 6, diabetic rats receiving 10 and 20 mg/kg of aminoguanidine daily,
      respectively. In each rat an implant was inserted in the femur. After 28 d of
      healing, the rats were killed. The implants were removed by applying a counter
      torque, and the maximum force required for the rupture of the bone-implant
      interface was recorded using an analog torque meter. The data were evaluated
      using analysis of variance and the Student's t-test. RESULTS: In the healthy
      groups, no statistically significant difference could be observed in the average
      counter-torque values for implant removal, whereas in the diabetic groups, a
      daily dose of 20 mg/kg of aminoguanidine raised the counter-torque values to the
      values found in healthy rats. CONCLUSION: The administration of 20 mg/kg of
      aminoguanidine daily in diabetic rats raised the biomechanical retention of the
      implants to the level observed in the healthy rat group.

PMID- 21732948
TI  - Establishment of the first international repository for transfusion-relevant
      bacteria reference strains: ISBT working party transfusion-transmitted infectious
      diseases (WP-TTID), subgroup on bacteria.
AB  - BACKGROUND: Bacterial contamination of platelet concentrates (PCs) still remains
      a significant problem in transfusion with potential important clinical
      consequences, including death. The International Society of Blood Transfusion
      Working Party on Transfusion-Transmitted Infectious Diseases, Subgroup on
      Bacteria, organised an international study on Transfusion-Relevant Bacteria
      References to be used as a tool for development, validation and comparison of
      both bacterial screening and pathogen reduction methods. MATERIAL AND METHODS:
      Four Bacteria References (Staphylococcus epidermidis PEI-B-06, Streptococcus
      pyogenes PEI-B-20, Klebsiella pneumoniae PEI-B-08 and Escherichia coli PEI-B-19)
      were selected regarding their ability to proliferate to high counts in PCs and
      distributed anonymised to 14 laboratories in 10 countries for identification,
      enumeration and bacterial proliferation in PCs after low spiking (0.3 and 0.03
      CFU/ml), to simulate contamination occurring during blood donation. RESULTS:
      Bacteria References were correctly identified in 98% of all 52 identifications.
      S. pyogenes and E. coli grew in PCs in 11 out of 12 laboratories, and K.
      pneumoniae and S. epidermidis replicated in all participating laboratories. The
      results of bacterial counts were very consistent between laboratories: the 95%
      confidence intervals were for S. epidermidis: 1.19-1.32 * 10(7) CFU/ml, S.
      pyogenes: 0.58-0.69 * 10(7) CFU/ml, K. pneumoniae: 18.71-20.26 * 10(7) CFU/ml and
      E. coli: 1.78-2.10 * 10(7) CFU/ml. CONCLUSION: The study was undertaken as a
      proof of principle with the aim to demonstrate (i) the quality, stability and
      suitability of the bacterial strains for low-titre spiking of blood components,
      (ii) the property of donor-independent proliferation in PCs, and (iii) their
      suitability for worldwide shipping of deep frozen, blinded pathogenic bacteria.
      These aims were successfully fulfilled. The WHO Expert Committee Biological
      Standardisation has approved the adoption of these four bacteria strains as the
      first Repository for Transfusion-Relevant Bacteria Reference Strains and,
      additionally, endorsed as a project the addition of six further bacteria strain
      preparations suitable for control of platelet contamination as the next step of
      enlargement of the repository.

PMID- 21732949
TI  - Food reinforcement effects on tympanic membrane temperature in response to
      restraint stress in Garnett's bushbaby (Otolemur garnettii).

PMID- 21732950
TI  - Increased inherent intestinal granzyme B expression may be associated with SIV
      pathogenesis in Asian non-human primates.
AB  - BACKGROUND: Unlike Asian non-human primates, chronically SIV-infected African non
      human primates (NHP) display a non-pathogenic disease course. The different
      outcomes may be related to the development of an SIV-mediated breach of the
      intestinal mucosa in the Asian species that is absent in the African animals.
      METHODS: To examine possible mechanisms that could lead to the gut breach, we
      determined whether the colonic lamina propria (LP) of SIV-naive Asian monkeys
      contained more granzyme B (GrB) producing CD4 T cells than did that of the
      African species. GrB is a serine protease that may disrupt mucosal integrity by
      damaging tight junction proteins. RESULTS: We found that the colonic LP of Asian
      NHP contain more CD4(+) /GrB(+) cells than African NHP. We also observed reduced
      CD4 expression on LP T cells in African green monkeys. CONCLUSION: Both
      phenotypic differences could protect against SIV-mediated damage to the
      intestinal mucosa and could lead to future therapies in HIV(+) humans.

PMID- 21732951
TI  - New approach for graded compression spinal cord injuries in Rhesus macaque:
      method feasibility and preliminary observations.
AB  - BACKGROUND: Current models of spinal cord injury (SCI) have been ineffective for
      translational research. Primate blunt SCI, which more closely resembles human
      injury, could be a promising model to fill this gap. METHODS: Graded compression
      SCI was produced by inflating at T9 an epidural balloon as a function of spinal
      canal dimensions in a non-uniform group of monkeys. RESULTS: Sham injury and cord
      compression by canal invasion of 50-75% produced minimal morpho-functional
      alterations, if at all. Canal invasion of 90-100% resulted in proportional
      functional deficits. Unexpectedly, these animals showed spontaneous gradual
      recovery over a 12-week period achieving quadruped walking, although with
      persistent absence of foot grasping reflex. Histopathology revealed predominance
      of central cord damage that correlated with functional status. CONCLUSIONS: Our
      preliminary results suggest that this model could potentially be a useful
      addition to translational work, but requires further validation by including
      animals with permanent injuries and expansion of replicates.

PMID- 21732952
TI  - Preliminary pharmacokinetics and cardiovascular effects of fenoldopam continuous
      rate infusion in six healthy dogs.
AB  - Fenoldopam is a selective dopamine-1 receptor agonist that causes peripheral
      arterial vasodilation, increased renal blood flow, and diuresis. Enthusiasm
      exists for the use of fenoldopam in nonpolyuric kidney injury in dogs, although
      pharmacokinetic data are lacking. The purpose of this study was to collect basic
      pharmacokinetic and hemodynamic effect data for fenoldopam when administered to
      healthy awake dogs. Six healthy, awake beagles were given a 180-min fenoldopam
      constant rate infusion at 0.8 MUg/kg per minute followed by a 120-min washout
      period. Citrated blood was collected during and after infusion for the
      measurement of plasma fenoldopam concentration by HPLC with mass spectrometry.
      Heart rate and indirect systolic blood pressure were concurrently measured. Mean
      +/- SD, steady-state plasma fenoldopam concentrations of 20 +/- 17 ng/mL were
      achieved within 10 min of starting the infusion. Area under the plasma
      concentration-time curve was 3678 +/- 3030 ng/mL . min, and plasma clearance was
      66 +/- 43 mL/min per kg. Elimination was rapidly achieved in all dogs. Heart rate
      and systolic blood pressure were unaffected by the fenoldopam infusion. Based on
      the results of this study, further evaluation of the effects of fenoldopam in
      dogs at differing doses and in dogs with clinical conditions such as acute
      nonpolyuric kidney injury is warranted.

PMID- 21732953
TI  - Metabolic surgery for type 2 diabetes.
AB  - Conventional bariatric operations, including Roux-en-Y gastric bypass (RYGB),
      laparoscopic adjustable gastric banding, and biliopancreatic diversion (BPD)
      appear to be a safe and effective treatment for many severely obese patients with
      type 2 diabetes mellitus (T2DM). These operations improve glucose homeostasis
      through a variety of mechanisms, however, not only due to reduced food intake and
      body weight. Research to elucidate the weight-independent antidiabetic mechanisms
      of gastrointestinal (GI) surgery and to clarify the molecular mechanisms
      responsible for the benefits of GI surgery on glucose homeostasis is a compelling
      research objective. We review the existing knowledge regarding the clinical
      outcomes and of the mechanisms of GI surgery to treat T2DM.

PMID- 21732954
TI  - Effect of plunger diameter on the push-out bond values of different root filling
      materials.
AB  - AIMS: To evaluate the effect of plunger diameter on the push-out bond strength of
      different root filling materials to root canal dentine. METHODOLOGY: Freshly
      extracted human incisors (n=90) were decoronated, and the root canals were
      enlarged with post drills. Prepared roots were placed into a custom alignment
      apparatus to embed the roots vertically within self-curing acrylic resin. The
      specimens were randomly assigned into three groups according to the root filling
      system used: gutta-percha/AH Plus; Resilon/Epiphany; and fibre-reinforced
      composite (FRC)/Duolink resin cement. After filling, the specimens were further
      subdivided according to the diameter of the plunger used to employ the debonding
      force: 0.75, 1 and 1.25 mm. Intra-radicular bond strength was measured using the
      push-out test at a cross-head speed of 1 mm min(-1) . The data were analysed
      statistically using Kruskal-Wallis test with Bonferroni correction at P = 0.05.
      RESULTS: Regardless of the plunger diameter, FRC yielded the highest bond
      strength, followed by gutta-percha and Resilon, respectively (P<0.001). In all
      groups, greater plunger diameter resulted in an apparent increased bond strength,
      but the differences were only significant in the FRC group, with the 1.25-mm
      plunger generating higher debonding values compared with that of its 0.75- and 1
      mm versions (P<0.001). In the gutta-percha and Resilon groups, the majority of
      specimens had adhesive failures. Roots filled with FRC exhibited more cohesive
      failures than those of the other test groups. CONCLUSIONS: Different plunger
      diameters are associated with significantly different intra-radicular push-out
      bond strengths of root filling systems.

PMID- 21732955
TI  - Tissue engineering human small-caliber autologous vessels using a xenogenous
      decellularized connective tissue matrix approach: preclinical comparative
      biomechanical studies.
AB  - Suggesting that bioartificial vascular scaffolds cannot but tissue-engineered
      vessels can withstand biomechanical stress, we developed in vitro methods for
      preclinical biological material testings. The aim of the study was to evaluate
      the influence of revitalization of xenogenous scaffolds on biomechanical
      stability of tissue-engineered vessels. For measurement of radial distensibility,
      a salt-solution inflation method was used. The longitudinal tensile strength test
      (DIN 50145) was applied on bone-shaped specimen: tensile/tear strength
      (SigmaB/R), elongation at maximum yield stress/rupture (DeltaB/R), and modulus of
      elasticity were determined of native (NAs; n = 6), decellularized (DAs; n = 6),
      and decellularized carotid arteries reseeded with human vascular smooth muscle
      cells and human vascular endothelial cells (RAs; n = 7). Radial distensibility of
      DAs was significantly lower (113%) than for NAs (135%) (P < 0.001) or RAs (127%)
      (P = 0.018). At levels of 120 mm Hg and more, decellularized matrices burst (120,
      160 [n = 2] and 200 mm Hg). Although RAs withstood levels up to 300 mm Hg, ANOVA
      revealed a significant difference from NA (P = 0.018). Compared with native
      vessels (NAs), SigmaB/R values were lower in DAs (44%; 57%) (P = 0.014 and P =
      0.002, respectively) and were significantly higher in RAs (71%; 83%) (both P <
      0.001). Similarly, DeltaB/R values were much higher in DAs compared with NAs
      (94%; 88%) (P < 0.001) and RAs (87%; 103%) (P < 0.001), but equivalent in NAs and
      RAs. Modulus of elasticity (2.6/1.1/3.7 to 16.6 N/mm(2)) of NAs, DAs, RAs was
      comparable (P = 0.088). Using newly developed in vitro methods for small-caliber
      vascular graft testing, this study proved that revitalization of decellularized
      connective tissue scaffolds led to vascular graft stability able to withstand
      biomechanical stress mimicking the human circulation. This tissue engineering
      approach provides a sufficiently stable autologized graft.

PMID- 21732956
TI  - Independence of bacteria on phytoplankton? Insufficient support for Fouilland &
      Mostajir's (2010) suggested new concept.
AB  - In a recent review, Fouilland & Mostajir questioned the direct dependence of
      bacterioplankton on phytoplankton based on a dataset of total primary production
      (particulate plus dissolved) and bacterial carbon demand (bacterial production
      plus respiration) estimated rates. We point out two problems for this
      interpretation. Firstly, there is considerable uncertainty in the authors'
      application of conversion factors to raw data and modelled rates so that the
      shape of the scatterplots can be substantially altered. Secondly, the current
      conceptual view of dissolved organic carbon lability and its temporal and spatial
      variations still provides enough support for the accepted paradigm.

PMID- 21732958
TI  - A comparison of three continuous scales used to determine the prevalence of
      clinically significant dental fear.
AB  - OBJECTIVE: To assess the level of agreement and concordance of three different
      dental anxiety and fear scales and determine whether using commensurate cut
      points reduces discrepancies in the estimated prevalence of high dental fear.
      METHODS: A representative sample of the Australian adult population completed a
      computer-assisted telephone interview (CATI) with additional data obtained on a
      random sample of 25% of those completing the CATI. Participants completed three
      measures of dental anxiety and fear: the Dental Anxiety Scale, the Index of
      Dental Anxiety and Fear, and a single-item question. Cut-points were determined
      to equivalize the range of possible score responses defining a case of high
      dental fear for each scale. RESULTS: A total of 1084 people completed the CATI
      and returned a questionnaire (response rate = 71.4%). Prevalence estimates ranged
      from 7.3% to 28.4% depending upon both the scale and cut-point used. The overall
      percent agreement between the scales was high, but the overlap between the scales
      in those people determined to have high dental fear was considerably lower. Using
      different cut-points to define a case significantly altered the sensitivity and
      specificity of the scale in predicting dental avoidance, problem-oriented
      visiting and fear of lack of control. CONCLUSIONS: Equivalizing scale cut-points
      does reduce variation in prevalence estimates of high dental fear across scales,
      but variation remains because of differences in the nature of, and content
      covered by, each scale. Dichotomizing scores on continuous scales to obtain
      prevalence estimates of high dental fear should be appropriately justified,
      correctly interpreted and supplemented by results describing the distribution of
      scores.

PMID- 21732959
TI  - A case of pityriasis rubra pilaris with associated focal acantholytic
      dyskeratosis complicated by Kaposi's varicelliform eruption.
AB  - The clinical and histopathological diagnosis of pityriasis rubra pilaris (PRP)
      can be difficult because clinical findings are often subtle in early stages, and
      microscopic findings can overlap with those of other skin diseases. Focal
      acantholytic dyskeratosis (FAD) can rarely be seen in PRP and can mimic Darier's
      disease, Grover's disease or other disorders characterized by these
      histopathologic features. Kaposi's varicelliform eruption is a widespread
      infection due to herpes simplex virus (HSV) types 1 and 2, coxsackievirus A16 or
      vaccinia virus, occurring in a preexisting dermatosis; only one case has been
      reported in PRP. We report a patient with PRP whose biopsies showed both herpes
      simplex infection and FAD. A complete understanding of the mechanism behind this
      eruption evolved gradually, aided in great measure by the histopathologic
      findings.

PMID- 21732960
TI  - Evaluation of the ability of neurobiological, neurodevelopmental and socio
      economic variables to predict cognitive outcome in premature infants.
AB  - BACKGROUND: When developed in the 1990s, the Neurobiologic Risk Score (NBRS) and
      Neurodevelopmental Risk Exam (NRE) correlated well with developmental outcomes in
      premature infants. Given recent advances in neonatology, we assessed their
      present ability to predict cognitive outcome, alone and combined with socio
      economic factors. METHODS: One hundred and twenty-nine neonates <32 weeks
      gestational age were assessed at 6, 12 and/or 24 months corrected age with the
      Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale
      (CAT/CLAMS). Indices of socio-economic status included maternal education and
      marital status. RESULTS: At 24 months corrected age (n= 67), the NBRS (r=-0.5),
      maternal education (r= 0.46) and marital status (r= 0.37) correlated with the
      CAT/CLAMS. These correlations increased when NBRS and maternal education were
      combined (r= 0.63) and when specific NBRS components (intraventricular
      haemorrhage, periventricular leukomalacia, seizures) and maternal education were
      combined (r= 0.66). CONCLUSIONS: In the contemporary neonatal intensive care
      unit, measures used to predict cognitive outcome should incorporate both
      neurobiological risk factors and socio-economic variables.

PMID- 21732961
TI  - The ubiquitous plasmid pXap41 in the invasive phytopathogen Xanthomonas
      arboricola pv. pruni: complete sequence and comparative genomic analysis.
AB  - The complete DNA sequence of the 41 102-bp plasmid pXap41 from the invasive plant
      pathogen Xanthomonas arboricola pv. pruni CFBP 5530 was determined and its 44
      coding regions were annotated. Comparative analysis with 15 Xanthomonas plasmids
      and 19 complete genomes revealed that nearly one-fourth of this plasmid has high
      sequence identity to plasmid pXAC64 and an 8.8-kb chromosomal region of
      Xanthomonas axonopodis pv. citri strain 306 carrying genes that encode type III
      effectors and helper proteins. The presence of pXap41 in all X. arboricola pv.
      pruni genotypes was confirmed for eight strains by plasmid profiling and for 35
      X. arboricola pv. pruni isolates with a new plasmid multiplex PCR assay. This
      plasmid was not detected in any other X. arboricola pathovars (n=12), indicating
      the potential for the application of the pXap41 PCR method as a pathovar-level
      detection and identification tool.

PMID- 21732962
TI  - Enzymatic detachment of spore germlings in Magnaporthe oryzae.
AB  - Magnaporthe oryzae germlings tightly attach to the host surface by producing
      extracellular matrix (ECM) from germ tubes and appressoria, which are important
      for the early infection process. To understand the adhesion mechanisms of ECM
      during differentiation of infection structure, we evaluated the effects of
      various enzymes on M. oryzae germlings and the disease symptoms of the host
      plant, wheat. Treatment with beta-mannosidase, collagenase N-2, collagenase S-1,
      or gelatinase B at 1-h postinoculation (hpi) resulted in germling detachment,
      although producing normal appressoria. Treatment with matrix metalloproteinases
      (MMPs) at 6 hpi also caused germling detachment. Furthermore, we confirmed by the
      inoculation tests and scanning electron microscopy that the germlings on the
      wheat plant were removed and did not manifest pathogenicity on treatment with
      MMPs. The most effective MMPs were crude collagenase, collagenase S-1, and
      gelatinase B, suggesting that the application of MMPs is promising for crop
      protection from fungal diseases by its detachment action.

PMID- 21732963
TI  - The Rv1651c-encoded PE-PGRS30 protein expressed in Mycobacterium smegmatis
      exhibits polar localization and modulates its growth profile.
AB  - Sequencing analysis of the complete genome of Mycobacterium tuberculosis (Mtb)
      H37Rv resulted in the identification of a novel multigene, the PE family of
      genes. The genes of the largest PE_PGRS subfamily of the PE family are mainly
      restricted to pathogenic mycobacteria, and their exact role in the biology of Mtb
      is not clearly understood. Based on their sequence homology, PE_PGRS proteins
      were initially thought to serve common functions. However, studies on individual
      proteins reveal that the individual proteins of this subfamily could be
      performing several unrelated tasks. In the present study, we investigated the
      function of PE_PGRS30 by expressing it in Mycobacterium smegmatis. PE_PGRS30
      expression in M. smegmatis resulted in phenotypic changes with altered colony
      morphology and growth profile. The recombinant PE_PGRS30 showed polar
      localization and was found to be associated with the cell wall of M. smegmatis.
      Thus, the present study suggests that the prolonged lag phase of growth caused by
      the PE_PGRS30 may, in part, contribute to the latency of Mtb.

PMID- 21732964
TI  - Identification of the third type of PVL phage in ST59 methicillin-resistant
      Staphylococcus aureus (MRSA) strains.
AB  - The genes lukS-PV and lukF-PV for Panton-Valentine leukocidin (PVL) that confers
      high virulence to Staphylococcus aureus are located on the prophages (PVL phages)
      which have been classified into group 1 and 2 sfi21-like Siphoviridae. We report
      novel PVL phages lysogenized in ST59 methicillin-resistant Staphylococcus aureus
      (MRSA) strains isolated in Japan (JCSC7247) and Taiwan (JCSC5967). The genomes of
      phi7247PVL and phi5967PVL showed more than 99% identity, and the regions
      containing the five genes located at both ends of the prophages, int (integrase),
      hol (holin), ami (amidase), lukS-PV, and lukF-PV, are highly homologous to extant
      PVL phages. The genes for the structural module are less homologous to these
      phages, but are highly homologous to non-PVL phages belonging to group 3 Sfi21
      like Siphoviridae, for example phiN315. Subsequent PCR identification and
      nucleotide sequencing of an additional 11 Taiwanese ST59 MRSA isolates suggested
      they all carry the same phage as phi5967PVL, which differed from phi7247PVL by a
      single base. This study adds evidence to the notion that novel PVL phages would
      be generated through illegitimate recombination events by acquiring the region at
      which hol, ami, luk, and int genes would line up upon lytic growth, and suggests
      that the PVL-positive MRSA clones that have emerged worldwide may carry distinct
      phages.

PMID- 21732965
TI  - History, ethics, and the truth.

PMID- 21732966
TI  - Public health nurses tailor interventions for families at risk.
AB  - OBJECTIVES: To use structured clinical data from public health nurse (PHN)
      documentation to describe client risk, to describe family home visiting
      interventions, including tailoring, and to assess the associations between client
      risk and intervention tailoring. DESIGN AND SAMPLE: Retrospective cohort design.
      A cohort of 486 family home visiting clients who received at least 3 visits from
      PHNs in a local Midwest public health agency (2000-2005). MEASURES: Omaha System
      variables documenting assessments, interventions, and outcomes. A risk index was
      created to identify low- and high-risk clients. Descriptive and inferential
      methods were used to describe interventions, and to assess intervention tailoring
      between groups. INTERVENTION: Routine PHN family home visiting practice. RESULTS:
      The risk index meaningfully discriminated between groups. PHNs provided more
      visits and interventions to clients in the high-risk group, with variations in
      problem, category, and target by group, demonstrating that PHNs tailored
      interventions to address specific client needs. CONCLUSIONS: Standardized
      terminologies and structured clinical data are useful tools to support PHN
      practice, and may be useful to advance health care quality research, program
      evaluation, policy development, and population health outcomes.

PMID- 21732967
TI  - Self-reported cardiovascular risk factors in immigrants and Swiss nationals.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the prevalence of
      self-reported cardiovascular risk factors differs between immigrants and Swiss
      nationals. DESIGN AND SAMPLE: This study is a secondary data analysis of the
      Swiss Health Survey 2002, a cross-sectional survey. In total, 19,249 individuals
      living in Switzerland were included. MEASURES: The prevalence of hypertension,
      high cholesterol level, smoking, diabetes, overweight, low fruit and vegetable
      intake, and physical inactivity were calculated for major immigrant groups and
      Swiss nationals. Demographic data were used to control for age and socioeconomic
      status. RESULTS: Major immigrant groups were people from Italy, Germany, former
      Yugoslavia, Spain, Portugal, France, and Turkey. Compared with Swiss women, women
      from former Yugoslavia were more likely to have hypertension, and women from
      Germany were more likely to have high cholesterol levels. Women from Italy,
      former Yugoslavia, Spain, Portugal, and Turkey were more likely to show physical
      inactivity and (except Turkish women) to be overweight. Men from these countries
      (except Spanish men) were more likely to be overweight than Swiss men.
      CONCLUSIONS: Differences exist in the prevalence of modifiable cardiovascular
      risk factors between Swiss nationals and many of the immigrant groups. Age and
      socioeconomic status could only partly explain the differences.

PMID- 21732968
TI  - Use of the program explication method to explore the benefits of a service for
      homeless and marginalized young people.
AB  - Maintaining the alignment between the dynamic development of health and social
      services and the rapidly advancing scientific evaluation literature is a central
      challenge facing service administrators. We describe "program explication," a
      consulting method designed to assist services to identify and review implicit
      program logic assumptions against the evaluation literature. Program explication
      initially facilitates agency staff to identify and document service components
      and activities considered critical for improving client outcomes. Program
      assumptions regarding the relationship between service activities and client
      outcomes are then examined against available scientific evidence. We demonstrate
      the application of this method using an example of its use in reviewing a service
      for homeless young people operating in Melbourne, Australia, known as the Young
      People's Health Service (YPHS). The YPHS involved 21 activities organized within
      4 components. The intended benefits of each of the activities were coherently
      articulated and logically consistent. Our literature search revealed moderate to
      strong evidence for around 1 quarter of the activities. The program explication
      method proved feasible for describing and appraising the YPHS service
      assumptions, thereby enhancing service evaluability.

PMID- 21732969
TI  - Public health nurse perceptions of empowerment and advocacy in child health
      surveillance in West Ireland.
AB  - OBJECTIVE: The objective of this study was to analyze public health nurses'
      perceptions of empowerment and advocacy within a child health screening and
      surveillance program in West Ireland. DESIGN AND SAMPLE: This study combined both
      qualitative and quantitative research methods. A purposive sample of 9 public
      health nurses (PHNs) (phase 1) participated in 2 focus groups and a purposive
      sample of 43 clients attending the child health screening service completed a
      questionnaire (phase 2). MEASURES: Focus groups and Questionnaires were used.
      RESULTS: Thematic content analysis revealed that PHNs in the study did not
      perceive themselves to be empowered in their work. They attributed this to
      workload, lack of professional advocacy, and restricted access to power and
      opportunity, while also identifying the need for continued managerial support and
      feedback. CONCLUSIONS: The results suggest that PHNs need to be empowered in
      order to facilitate client empowerment. PHNs struggled with empowerment and
      client advocacy. There is a need for professional development for PHNs in order
      to support them to more critically engage with empowerment and self-efficacy in
      their work. This needs to be done within organizational structures that support
      PHNs to critically analyze the role of advocacy and empowerment in their
      practice.

PMID- 21732970
TI  - Friere's dialogic concept enables family health program teams to incorporate
      health promotion.
AB  - ABSTRACT Objective: The study analyzes the possibility of incorporating health
      promotion measures into the work processes of Family Health Program teams at a
      primary health care clinic in Brazil. DESIGN AND SAMPLE: We used the
      participatory research concept developed in 1968 by Freire. The study sample
      comprised the end-users of the health care system, together with 3
      multidisciplinary teams. A total of 77 health care users and 55 health
      professionals participated in the study. MEASURES: Culture circles composed of
      health care professionals, and users from different areas investigated generative
      topics, encoded/decoded topics, and engaged in critical probing for
      clarification. Topics affecting quality of life and health were heuristically
      evaluated. RESULTS: Although most topics were related to changing the focus of
      health care facilities, some were related to subsidizing community-based
      interventions, improving environmental strategies, individual skills, and public
      policies. Incorporating the novel health promotion measures and creating an
      expanded full-treatment clinic are important steps toward that goal. CONCLUSIONS:
      Topics that can stimulate dialogue among the members of the culture circles
      include creating an environment of closer cultural contact, with repercussions
      for work processes, family health models, and general health models, as well as
      the inclusion of social aspects in the decision-making processes related to
      health issues that affect the living conditions of the population.

PMID- 21732971
TI  - Philosophical and ethical perspectives on cardiovascular disease risk in low-wage
      workers.
AB  - One of the overriding goals of Healthy People 2010 is to reduce the health
      disparities observed among Americans. Because workers in small businesses tend to
      have little or no access to health screening or preventive health education
      programs, they may be unaware of their unique risk factors and are thus more at
      risk of cardiovascular disease (CVD). Furthermore, occupational health nurses are
      more likely to be available in health programs to employees in large rather than
      small businesses. The purpose of this paper is to illustrate how nursing values
      and philosophy might influence public health nurses' thinking about nursing
      science and ethical issues relating to the risk of CVD among low-wage workers.
      The following questions will guide the exploration of health disparities among
      low-wage workers: (a) What are the health disparities observed among low-wage
      workers with CVD risk? (b) What are the philosophical and ethical perspectives on
      the issues presented? (c) Based on these findings, how should limited resources
      be allocated? and (d) How does this affect nursing? These approaches will provide
      the foundation for developing a culturally sensitive ethical and philosophical
      perspective to prevent CVD and promote cardiovascular health among low-wage
      workers.

PMID- 21732972
TI  - The skills gap in nursing management in the South African public health sector.
AB  - OBJECTIVES: Nurse managers are central to health delivery in South Africa.
      However, there is a paucity of research that analyzes their competence to
      successfully discharge their managerial role. To identify the competencies
      perceived to be important for effective nursing management in the South African
      public sector and the managers' self-assessed proficiency in these. DESIGN AND
      SAMPLE: A cross-sectional survey using a self-administered questionnaire. 215
      senior nursing managers at South African public sector hospitals. MEASURES:
      Respondents rated the level of importance that 51 proposed competencies had in
      their job and indicated their proficiency in each. RESULTS: Public sector
      managers ranked controlling as the most important competency, followed by
      leading, organizing, and self-management. Health/clinical skills, planning, and
      legal/ethical competencies were ranked as being relatively less important. They
      assessed themselves as being most competent in self-management, followed by
      planning, controlling, leading, and specific health skills. The competency gap
      was the largest for legal/ethical issues, organizing, and controlling. The
      competency gap for planning and self-management was relatively smaller.
      CONCLUSIONS: This research confirms that there is a lack of management capacity
      within the public health sector and also identifies the areas in which the lack
      of knowledge or skills is most significant.

PMID- 21732973
TI  - Photovoice engages rural youth in childhood obesity prevention.
AB  - Photovoice is a participatory action research methodology that involves the use
      of photography and enables people to document, reflect upon, and communicate
      community needs to policymakers for the purpose of promoting social change. We
      describe how Photovoice was used to engage rural youth in childhood obesity
      prevention research and obtain their perspectives of community assets and
      barriers that influenced children's physical activity and diets in their county.
      The photographs and stories produced by the youth garnered public interest and
      were beneficial in raising community awareness of community conditions that may
      contribute to childhood obesity and the need for environmental change.
      Utilization of the method also provided a beneficial leadership experience for
      the youth participants.

PMID- 21732974
TI  - Predictive factors of the nursing diagnosis sedentary lifestyle in people with
      high blood pressure.
AB  - OBJECTIVES: To verify the reproducibility of defining the characteristics and
      related factors in order to identify a sedentary lifestyle in patients with high
      blood pressure. DESIGN AND SAMPLE: A cross-sectional study. 310 patients
      diagnosed with high blood pressure. MEASURES: Socio-demographics and variables
      related to defining the characteristics and related factors of a sedentary
      lifestyle. The coefficient Kappa was utilized to analyze the reproducibility. The
      sensitivity, specificity, and predictive value of the defining characteristics
      were also analyzed. Logistic regression was applied in the analysis of possible
      predictors. RESULTS: The defining characteristic with the greatest sensitivity
      was demonstrates physical deconditioning (98.92%). The characteristics chooses a
      daily routine lacking physical exercise and verbalizes preference for activities
      low in physical activity presented higher values of specificity (99.21% and
      95.97%, respectively). CONCLUSIONS: The following indicators were identified as
      powerful predictors (85.2%) for the identification of a sedentary lifestyle:
      demonstrates physical deconditioning, verbalizes preference for activities low in
      physical activity, and lack of training for accomplishment of physical exercise.

PMID- 21732975
TI  - Time of initiation of skin-to-skin contact in extremely preterm infants in
      Sweden.
AB  - AIM: To describe the time of first skin-to-skin contact in extremely preterm
      infants in a national perspective and to investigate possible factors affecting
      the time of first skin-to-skin contact. METHODS: A population-based prospective
      descriptive study of extremely preterm infants (n = 520) in seven regional
      hospitals in Sweden. RESULTS: Extremely preterm infants in Sweden experience
      first skin-to-skin contact with the parent at a median of six postnatal days
      (range 0-44). Low gestational age, a high score on the clinical risk index for
      babies, and the number of days on a ventilator tended to delay first skin-to-skin
      contact. A statistically significant difference was also found between regional
      hospitals. CONCLUSION: There is a difference in the time of first skin-to-skin
      contact based on the infant's medical condition and the tradition in the neonatal
      intensive care unit at the regional hospital where the infant is born.

PMID- 21732976
TI  - The effect of olfactory stimulation on energy expenditure in growing preterm
      infants.
AB  - AIM: To test the hypothesis that olfactory stimulation in growing healthy preterm
      infants leads to an increase in resting energy expenditure (REE). DESIGN: A
      prospective, randomized clinical trial with crossover was conducted in 20
      healthy, appropriate weights for gestational age, gavage-fed preterm infants.
      Infants were studied while asleep and cared for in a skin servo-controlled
      convective incubator. Using a pipette, 15 drops of saturated solution of vanillin
      (Aldrich, Fallavier, France) were dripped to a cloth diaper that was placed on
      the opposite side of the incubator. REE was measured by indirect calorimetry
      (DeltaTrac II, Helsinki, Finland) exactly 1 h after feeding. Each infant was
      studied twice by randomization: after a period of 20 min of vanillin odour or
      after 20 min without vanillin odour. RESULTS: We found no statistically
      significant difference in REE of preterm infants when exposed to vanillin odour
      (74.5 +/- 10.1 kcal/kg/day) in comparison with their REE when not exposed to
      vanillin odour (79.0 +/- 11.3 kcal/kg/day). CONCLUSIONS: Vanillin odour does not
      significantly influence REE in metabolically and thermally stable preterm
      infants.

PMID- 21732977
TI  - Omega-3 polyunsaturated essential fatty acids are associated with depression in
      adolescents with eating disorders and weight loss.
AB  - AIM: To study the relationship between polyunsaturated fatty acids (PUFA) status
      and depression in adolescents with eating disorders (ED) and weight loss.
      METHODS: Erythrocyte membranes from 217 adolescents (209 girls, eight boys) with
      ED were analysed for fatty acids (FA). ED and depression were diagnosed by
      clinical interviews and supported by self-report instruments. RESULTS:
      Adolescents with ED and depression did not differ from those with ED only in
      terms of age, BMI, weight loss and duration of disease. In their FA profile,
      depressed adolescents had lower proportions of eicosapentanoic acid (EPA) and
      docosahexanoic acid (DHA), the end products of the omega3 PUFA series. The ratio
      of long-chain (>18 carbons) omega6/omega3 PUFA was therefore higher in depressed
      adolescents. Indices of desaturase activities did not differ between depressed
      and not depressed adolescents. CONCLUSION: Low omega3 status is related to
      depression in adolescents with ED. This cannot be explained by differences in
      weight (loss) and duration of disease, nor by differences in PUFA processing by
      desaturases. Data suggest a lower dietary intake of omega3 PUFA in those with
      depression. Further investigations should determine whether omega3 PUFA status
      improves by refeeding only or whether supplementation with PUFA is warranted.

PMID- 21732978
TI  - Impact of the new european paediatric regulatory framework on ethics committees:
      overview and perspectives.
AB  - AIM: To evaluate the impact of the new European paediatric regulatory framework
      on the activities of Ethics Committees operating in Europe and to assess their
      involvement and interest in paediatric research. METHODS: Task-force in Europe
      for Drug Development for the Young Network of Excellence and Relating
      Expectations and Needs to the Participation and Empowerment of Children in
      Clinical Trials project set up an inventory of Ethics Committees existing in
      Europe and conducted a survey on their approach to paediatric trials. RESULTS:
      Ethics Committees operating in 22 European Countries participated in this survey.
      Results showed a high lack of knowledge, understanding and awareness of the
      current European paediatric regulatory framework and a lack of involvement of
      Ethics Committees in paediatric research, especially in terms of training and
      education, demonstrated also by the decreasing number of Ethics Committees
      answering exhaustively to the whole questionnaire. The majority of participating
      Ethics Committees expressed interest in future initiatives related to paediatric
      research. CONCLUSIONS: Despite a limited knowledge and understanding of the
      current paediatric regulatory framework, a significant number of Ethics
      Committees operating in Europe show interest in initiatives related to paediatric
      research. Networking may be an essential tool to be used to enhance Ethics
      Committees role in supporting paediatric research. Any initiative should be
      undertaken at European level in collaboration with European Union Institutions.

PMID- 21732979
TI  - Differential host susceptibility to Batrachochytrium dendrobatidis, an emerging
      amphibian pathogen.
AB  - The amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) has received
      considerable attention due to its role in amphibian population declines
      worldwide. Although many amphibian species appear to be affected by Bd, there is
      little information on species-specific differences in susceptibility to this
      pathogen. We used a comparative experimental approach to examine Bd
      susceptibility in 6 amphibian species from the United States. We exposed
      postmetamorphic animals to Bd for 30 days and monitored mortality, feeding rates,
      and infection levels. In all species tested, Bd-exposed animals had higher rates
      of mortality than unexposed (control) animals. However, we found differences in
      mortality rates among species even though the amount of Bd detected on the
      different species' bodies did not differ. Of the species tested, southern toads
      (Anaxyrus terrestris) and wood frogs (Lithobates sylvaticus) had the highest
      rates of Bd-related mortality. Within species, we detected lower levels of Bd on
      individuals that survived longer and found that the relationship between body
      size and infection levels differed among species. Our results indicate that, even
      under identical conditions, amphibian species differ in susceptibility to Bd.
      This study represents a step toward identifying and understanding species
      variation in disease susceptibility, which can be used to optimize conservation
      strategies.

PMID- 21732980
TI  - Negative effects of habitat loss on survival of migrant Warblers in a forest
      mosaic.
AB  - Habitat loss and fragmentation in forested landscapes often negatively affect
      animal abundance; however, whether these factors also affect fitness is not well
      known. We hypothesized that observed decreases in bird occurrence and abundance
      in landscapes with harvested forests are associated with reduced apparent
      survival of adults. We defined apparent survival as an estimate of survival that
      accounts for an imperfect resighting probability, but not permanent emigration
      (i.e., dispersal). We examined the association between spatially extensive
      habitat loss and apparent survival of males of 2 Neotropical migrant species,
      Blackburnian Warbler (Dendroica fusca) and Black-Throated Green Warbler (D.
      virens), over 7 years in the Greater Fundy Ecosystem, New Brunswick, Canada. We
      estimated apparent survival among and within breeding seasons. We quantified
      amount of habitat in the context of individual species. In this landscape,
      boundaries between land-cover types are gradual rather than clearly identifiable
      and abrupt. Estimated apparent within-season survival of both species decreased
      as a function of amount of habitat within a 2000-m radius; survival was
      approximately 12 times (95% CI 3.43-14) greater in landscapes with 85% habitat
      than in landscapes with 10% habitat. Apparent annual survival also decreased as a
      function of amount of habitat within a 100-m radius. Over the range of habitat
      amount, apparent annual survival decreased 15% (95% CI 7-29%) as the amount of
      habitat decreased. Our results suggest that reduced species occurrence in
      landscapes with low proportions of habitat is due partly to lower apparent
      survival at these sites. This mechanism operates both directly (i.e., via effects
      on mortality or dispersal during breeding) and possibly through indirect effects
      during the nonbreeding season. Habitat loss was associated not only with a lower
      number of individuals, but also with lower survival of those individuals.

PMID- 21732981
TI  - Comparison of the occurrence of mold infection among patients receiving
      chemotherapy for acute leukemia versus patients undergoing stem cell
      transplantation.
AB  - OBJECTIVES: Invasive mold infections (IMI) are an important cause of morbidity
      and mortality in patients with hematological malignancies. Cumulative incidence
      numbers vary greatly, probably because local circumstances influence the
      incidence of IMI. Therefore, comparison of different patient groups at risk
      should be performed at one hospital. METHODS: We performed a single-center
      retrospective analysis examining both adult patients treated with chemotherapy
      for acute leukemia or MDS and patients undergoing allogeneic or autologous stem
      cell transplantation (SCT) between June 2007 and August 2009. IMI were classified
      according to the EORTC criteria. RESULTS: A total of 211 patients with 237
      predefined risk episodes were analyzed. A total of 22 IMI were observed: three of
      them were classified as proven, 15 as probable, and four as possible. No IMI were
      observed in the autologous SCT group. The incidence of proven and probable IMI in
      the allogeneic SCT group was 7.2%, and in the chemotherapy group, 14.3%. Patients
      with IMI had a higher mortality risk. CONCLUSIONS: We demonstrate for the first
      time that patients receiving intensive chemotherapy for acute leukemia have the
      highest risk of developing IMI during their treatment compared to patients with
      allogeneic SCT.

PMID- 21732982
TI  - One-year clinical and radiographic assessment of fluoride-enhanced implants on
      immediate non-functional loading in posterior maxilla and mandible: a pilot
      prospective clinical series study.
AB  - OBJECTIVE: The functional, esthetic, and psychological problems of 3-6 months of
      edentulousness and also discomfort of two-stage surgery might cause many patients
      to avoid implant-supported restorations. Therefore, the immediate non-functional
      loading protocol might be of value. METHODS: Twenty Astra Tech implants, 11-13 mm
      in length and 3.5-4 mm in diameter, were placed in maxillary and mandibular
      posterior sites of 10 healthy patients (two for each) with adequate alveolar
      bone. Temporary prostheses were relieved of all centric and eccentric contacts.
      Functional permanent prostheses were fabricated 13 weeks postoperatively.
      Clinical and radiographic examinations (including the implant stability quotient
      [ISQ]) were carried out immediately after implantation and 3, 6, and 12 months
      postoperatively. RESULTS: A 100% success rate was observed within 1 year. The
      plaque and bleeding indices, and pocket-probing depths did not show a significant
      change throughout the study. The ISQ values after implant insertion, and 3, 6,
      and 12 months later were respectively 76.6 +/- 6.57, 77.6 +/- 10.54, 81.8 +/-
      6.8, and 82.43 +/- 3.7. The increase was statistically significant (P=0.004)
      according to the Freidman test. The ISQ values measured after the implant
      insertion were significantly different from those measured in the sixth and 12th
      postoperative months (P<0.008) according to the Wilcoxon signed-ranks test. The
      mean crestal alveolar bone resorption values in the third, sixth, and 12th
      postoperative months were 0.4 +/- 0.55, 0.48 +/- 0.37, and 0.48 +/- 0.21 mm,
      respectively; and the change in marginal alveolar bone loss was not significant
      according to the Freidman test. CONCLUSION: Within the limitations of this pilot
      study, non-functional immediate loading might meet the expectations of both the
      patients and clinicians.

PMID- 21732983
TI  - Bone healing of critical-sized nasal defects in rabbits by statins in two
      different carriers.
AB  - OBJECTIVES: To evaluate bone healing following implantation of a statin with two
      different carriers in rabbit nasal bone using histological and
      immunohistochemical methods. MATERIALS AND METHODS: Twenty adult, male Japanese
      white rabbits (age: 12-16 weeks, weight: 2.5-3 kg) were used in this study. Five
      bone circular defects (5 mm in diameter) per rabbit were created in the nasal
      bone while preserving the nasal membrane. In the experimental groups, 2.5 mg/ml
      simvastatin dissolved in 0.2 ml water with hydrogel was implanted in one group,
      2.5 mg/ml simvastatin dissolved in 0.2 ml water with an atelocollagen sponge
      (ACS) in the second group with, only the hydrogel in the third group and only an
      ACS in the fourth group. No material was implanted in the control group. Four
      animals were killed in each period, at 1, 2, 4, 8 and 12 weeks postoperatively.
      The parts that had been operated on were removed and prepared for histological
      assessment. The expression of bone morphogenetic proteins (BMP)-2 and the bone
      ration was evaluated using histological and immunohistochemical methods. RESULTS:
      No significant differences were observed between the simvastatin with hydrogel
      group and the simvastatin with ACS group at 1, 2, 4, 8 and 12 weeks
      postoperatively regarding expression of BMP-2, although the number of cells that
      stained positive for BMP-2 in both of the implanted groups increased
      significantly at 2 and 4 weeks postoperatively in comparison with the control
      group (P<0.0001). For new bone area ratio, there were no significant differences
      between the simvastatin with hydrogel groups and the simvastatin with ACS group
      after 2, 4, 8 and 12 weeks, although these groups showed higher value than
      control group (P<0.0001). CONCLUSION: This study suggests that both the
      simvastatin with hydrogel and simvastatin with ACS implants showed similar BMP-2
      expression and new bone formation, and there were no significant differences
      between the two carriers.

PMID- 21732984
TI  - Long-term follow-up of turned single implants placed in periodontally healthy
      patients after 16-22 years: radiographic and peri-implant outcome.
AB  - OBJECTIVES: Retrospectively evaluate the survival, radiographic and peri-implant
      outcome of single turned BranemarkTM implants after at least 16 years. MATERIALS
      AND METHODS: From 134 patients (C-group), 101 could be contacted concerning
      implant survival and 50 (59 remaining implants) were clinically examined (I
      group). Marginal bone level was radiographically measured from the implant
      abutment junction at baseline (=within 6 months after abutment connection) and 1
      4, 5-8 and 16-22 years post-operatively. Probing depth, gingival and plaque index
      were measured. Marginal bone-level changes were analyzed using Friedman's and
      Wilcoxon's signed ranks tests. Spearman's correlations between radiographic and
      clinical parameters were calculated. RESULTS: In the C-group, 13 out of 166
      implants in 11 out of 134 patients failed (CSR=91.5%). In the I-group (28 males
      22 females; mean age 23.9 years at baseline; range 14-57), the mean follow-up was
      18.4 years (range 16-22). The mean bone level was 1.7+/-0.88 mm (range -0.8 to 5)
      after 16-22 years. Changes in the mean marginal bone level were statistically
      significant between baseline and the second measuring interval (1-4 years).
      Thereafter, no significant differences could be demonstrated. The mean
      interproximal probing depth, gingival and plaque indices were 3.9+/-1.27 mm,
      1.2+/-0.81 and 0.2+/-0.48, respectively. Probing depth was moderately correlated
      with gingival inflammation (r=0.6; P<0.001) but not with bone level (P>0.05).
      81.4% of the implants had a bone level <=2nd thread and 91.5% had a probing depth
      <=5 mm. 76.3% had both bone level <=2nd thread and probing depth <=5 mm.
      CONCLUSIONS AND CLINICAL IMPLICATIONS: The single turned BranemarkTM implant is a
      predictable solution with high clinical survival and success rates. In general, a
      steady-state bone level can be expected over decades, with minimal signs of peri
      implant disease. A minority (5%), however, presents with progressive bone loss.

PMID- 21732985
TI  - Patients with palmoplantar pustulosis have increased IL-17 and IL-22 levels both
      in the lesion and serum.
AB  - Recent findings about the pathogenesis of pustulosis palmaris et plantaris (PPP),
      also known as palmoplantar pustulosis, suggest that IL-17 expression in the
      acrosyringium as well as infiltration of IL-17 positive cells, e.g. Langerhans
      cells may play important roles. However, to date, it has not been established
      whether circulating IL-17 related cytokines are involved in PPP. We studied the
      circulating IL-17 related cytokines as well as the mRNA levels in lesional skin.
      IL-17 related cytokine mRNAs were increased in the PPP lesions compared with the
      control tissues (five patients vs five controls). The serum levels of TNF-alpha,
      IL-17, IL-22 and IFN-gamma also were significantly increased in PPP, but not IL
      23 and IL-8 (48 patients vs 20 controls). Our findings document that not only the
      serum IL-17 but also tissue IL-17 are elevated in PPP and may be in the
      pathogenesis of this disorder.

PMID- 21732986
TI  - LL-37 suppresses sodium nitroprusside-induced apoptosis of systemic sclerosis
      dermal fibroblasts.
AB  - The human cathelicidin antimicrobial peptide LL-37 regulates apoptosis of several
      cell types. Defective apoptosis of skin fibroblasts may contribute to systemic
      sclerosis (SSc). Here, we show that LL-37 inhibited apoptosis of SSc fibroblasts
      and identified the signalling pathways by which LL-37 mediates apoptosis.
      Immunohistochemistry showed that cathelicidin expression was enhanced in SSc
      patients compared with healthy controls. In addition, LL-37 decreased sodium
      nitroprusside (SNP)-induced apoptosis of SSc fibroblasts. LL-37 significantly
      increased expression of Bcl-2 and decreased levels of BAX protein. Pretreatment
      with LL-37 decreased activation of caspase-3 following SNP-treatment. Moreover,
      exposure of SSc fibroblasts to LL-37 resulted in increased expression of COX-2
      and stimulation of prostaglandin E(2) (PGE(2)). Furthermore, LL-37 induced
      phosphorylation of ERK and the ERK inhibitor PD98059 blocked the inhibitory
      effect of LL-37 on apoptosis. Our data indicate that LL-37 may be associated with
      skin sclerosis by inhibiting apoptosis of dermal fibroblasts.

PMID- 21732987
TI  - An enhanced risk of basal cell carcinoma is associated with particular
      polymorphisms in the VDR and MTHFR genes.
AB  - BACKGROUND: Vitamin D and folate are influenced by ultraviolet radiation (UVR),
      and both are implicated in skin carcinogenesis. Polymorphisms in the genes
      involved in the metabolism of these two compounds may alter the risk of basal
      cell carcinoma (BCC). OBJECTIVE: To assess the frequency of four polymorphisms in
      the gene encoding the vitamin D receptor (VDR) (FokI, BsmI, TaqI and ApaI) and
      two in the gene encoding methylenetetrahydrofolate reductase (MTHFR) (677C/T and
      1286A/C) in 142 patients of Polish origin with BCC and the same number of
      controls. The expression of VDR and MTHFR proteins in the skin, and the vitamin D
      status of a subset of patients and controls were also measured. PATIENTS/METHODS:
      The polymorphisms were assayed by PCR-RFLP, the VDR and MTHFR proteins by
      immunoblotting and vitamin D status as 25-hydroxyvitamin D (25(OH)D) level in the
      serum by RIA. RESULTS: The presence of the TT genotype in the FokI VDR
      polymorphism resulted in a >10-fold higher risk of BCC development. The CT
      genotype in 677C/T MTHFR polymorphism and CC genotype in 1286A/C MTHFR
      polymorphism also significantly increased the risk of BCC development. The
      expression of the VDR and MTHFR proteins was significantly higher in BCCs of the
      patients than in the healthy skin of the controls. The median serum level of
      25(OH)D was significantly higher in the control group compared with the patients
      with BCC. CONCLUSIONS: Certain VDR and MTHFR gene polymorphisms increase the risk
      of BCC development in individuals of Polish origin.

PMID- 21732988
TI  - Influence of heparan sulfate chains in proteoglycan at the dermal-epidermal
      junction on epidermal homeostasis.
AB  - Basement membrane (BM) plays important roles in skin morphogenesis and
      homeostasis by controlling dermal-epidermal interactions. However, it remains
      unclear whether heparan sulfate (HS) chains of proteoglycan in epidermal BM
      contribute to epidermal homeostasis. To explore the function of HS chains at the
      dermal-epidermal junction (DEJ), we used a skin equivalent (SE) model. This model
      lacked HS at the DEJ and showed abnormal expression of the differentiation
      markers filaggrin and loricrin; similar changes were seen in ultraviolet B
      irradiated human skin. Perlecan (core-protein of HS proteoglycan) remained
      localized at the DEJ in both SE and UV-irradiated human skin. Heparanase, which
      degrades HS, was increased in epidermis of UV-irradiated skin, compared with
      unirradiated skin. We found that deposition of HS at the DEJ in the SE model was
      markedly augmented by a synthetic heparanase inhibitor, and release of HS into
      conditioned medium was suppressed. The inhibitor also increased filaggrin and
      loricrin expression. Moreover, the recovery of HS was associated with an increase
      of Ki67-positive basal cells, compared with control SE cultured without
      inhibitor. Comparative gene expression analysis in epidermis of SE cultured in
      the presence and absence of heparanase inhibitor, using DNA microarrays, showed
      that recovery of HS was associated with increased expression of differentiation
      related genes and down-regulation of degradation-enzyme-related genes. These
      results indicate that degradation of HS at the DEJ by heparanase impairs
      epidermal homeostasis in SE, leading to abnormal differentiation and
      proliferation behaviour. Thus, HS chains in epidermal BM appear to play an
      important role in epidermal homeostasis.

PMID- 21732989
TI  - Lymphoplasmacyte-rich meningioma: a convexity mass with regional enhancement in
      the adjacent brain parenchyma.
AB  - Lymphoplasmacyte-rich meningioma (LPM) is a rare, benign variant of meningioma,
      characterized by massive inflammatory cell infiltration and a variable proportion
      of meningothelial tumorous elements. Here we report the clinicopathological
      features of an LPM located at the right frontal convexity in a 37-year-old woman.
      The patient had suffered an initial generalized tonic-clonic seizure when she was
      32 weeks pregnant. The lesion exhibited low intensity on T1-weighted MRI and high
      intensity on T2-weighted images, with surrounding parenchymal edema. The mass
      exhibited gadolinium enhancement with dural tail signs. Moreover, multiple foci
      of linear enhancement spreading through the sulci and into the nearby brain
      parenchyma were evident. At 1 month after parturition, en bloc removal of the
      mass, the attached dura mater and adjacent brain tissue was performed.
      Histologically, the mass located in the subdural space was composed of a mixture
      of B- and T-lymphocytes and plasma cells. Within the mass, multiple small lobules
      of meningothelial cells showing immunoreactivity for epithelial membrane antigen
      and vimentin were observed. The inflammatory cells had also infiltrated the
      subarachnoid and Virchow-Robin spaces, and the dura mater. The cerebral cortex
      showed ischemic changes, but no tumor cell invasion. On the basis of these
      histological features, the lesion appeared to be LPM with an inconspicuous
      meningothelial component and extensive inflammatory infiltration. This case
      appears to provide useful information on the pathogenesis of this variant.

PMID- 21732990
TI  - The diversities of PrP(Sc)  distributions and pathologic changes in various brain
      regions from a Chinese patient with G114V genetic CJD.
AB  - Human genetic Creutzfeldt-Jakob disease (gCJD; one of the prion diseases) is
      caused by point mutations and insertions in the prion protein gene (PRNP).
      Previously we have reported a Chinese gCJD case with a substitution of valine (V)
      for glycine (G) at codon 114. To investigate the detailed pathogenic and
      pathologic characteristics of G114V gCJD, 10 different brain regions were
      thoroughly analyzed. PrP-specific Western blots and immunohistochemical (IHC)
      assays identified larger amounts of PrP(Sc)  in the regions of brain cortex.
      Assays of the transcriptions of PrP-specific mRNA by RT-PCR and real-time PCR
      showed comparable levels in 10 brain regions. In line with the distribution of
      PrP(Sc) , typical vacuolations in brains, markedly in four cortex regions, were
      detected. Contrast to the distributing features of spongiform and of PrP(Sc) ,
      massive gliosis was detected in all brain regions by GFAP-specific IHC tests.
      Moreover, two-dimensional gel immunoblots found three major sets of PrP(Sc) 
      spots, indicating that PrP(Sc)  in brain tissues was a mixture of molecules with
      different biochemical properties. The data here provide the pathogenic and
      neuropathological features of G114V gCJD.

PMID- 21732991
TI  - Low-grade malignant triton tumor in the lumbar spine: a rare variant of malignant
      peripheral nerve sheath tumor with rhabdomyoblastic differentiation.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is an uncommon type of sarcoma
      that arises from peripheral nerve sheaths and rarely involves the spinal roots.
      The origin of this tumor is thought to be Schwann cells or pluripotent cells of
      the neural crest. The subgroup of tumors in which malignant Schwann cells coexist
      with malignant rhabdomyoblasts is termed malignant triton tumor (MTT). MPNSTs can
      show different degrees of malignancy, but overall spinal MTTs are high-grade
      lesions. We report the exceptional instance of a spinal low-grade MTT in a 39
      year-old man treated with total surgical removal followed by local radiation
      therapy. Histological low grade was based on the lack of necrosis, a low grade of
      atypia, a low mitotic rate and a Ki-67 labelling index <25%. After 18 months of
      follow-up the patient is alive with no evidence of disease. A thorough review of
      the literature yielded 57 well-documented spinal MPNSTs. Ten of them corresponded
      to MTTs, but none showed low-grade features. An analysis of the clinical,
      radiological and treatment data was performed to identify factors that might
      influence the outcome. Overall the 18-month survival rate was 45% but dropped to
      0% in the subgroup of spinal MTTs. Besides, a size exceeding 2 cm, extra-spinal
      extension, association with neurofibromatosis and subtotal removal were all
      related to a worse outcome. In conclusion, spinal MTTs generally exhibit a more
      aggressive behavior than conventional MPNSTs. The occurrence of a spinal low
      grade MTT with a better prognosis should also be recognized.

PMID- 21732992
TI  - Condensing results of wet sieving analyses into a single data: a comparison of
      methods for particle size description.
AB  - Sieve analysis is used in feed analysis, and studies of digestive physiology with
      various approaches to describe an average value of particle size which can serve
      to compare different samples. To demonstrate the effects of such different
      approaches, we compared five particle size indicators to demonstrate advantages
      and disadvantages of each method, the modulus of fineness (MOF), the discrete
      mean (dMEAN) and median (dMED), and the continuous mean (cMEAN) and median
      (cMED), well aware of the fact that a gold standard for this procedure is
      lacking. Data were obtained from 580 individual faecal samples of different
      herbivore species by wet sieving over a cascade of nine sieves with mesh sizes
      ranging from 0.063 to 16 mm. MOF, dMEAN and dMED can be calculated directly from
      the results of sieve analysis, but cMEAN and cMED require a curve-fitting
      procedure. Across the whole sample size, dMEAN and cMEAN showed the highest
      correlation. The correlation between the respective MEAN and MED was higher for d
      than for c. As expected, MOF deviated most from the other measurements.
      Simulating different sieve sets resulted in a poor correlation between the
      results from the different sets in MOF and cMED, but a good correlation in dMEAN
      and cMEAN, suggesting that these latter measures can also be compared between
      studies that do not use identical sieve sets. As the calculation of dMEAN is
      comparatively simpler and less time-consuming than that of cMEAN, we propose the
      dMEAN as a standard for the description of a mean particle size value obtained
      from sieve analysis. For practical application, the good correlation of different
      simulated sieve sets indicates that sets with fewer sieves could be used in large
      scale studies to reduce analytical workload.

PMID- 21732994
TI  - Effects of glucose, propionate and splanchnic hormones on neuropeptide mRNA
      concentrations in the ovine hypothalamus.
AB  - The capacity for glucose, propionate or hormones of splanchnic origin to
      influence appetite by directly regulating the expression of neuropeptides in the
      feeding centres of the hypothalamus of the ruminant is not described. Therefore,
      our objective was to measure the direct effect of metabolites (glucose and
      propionate) or hormones [insulin, cholecystokinin (CCK), glucagon-like peptide-1
      (GLP-1) and polypeptide YY (PYY)] on hypothalamic mRNA concentrations for
      neuropeptide Y (NPY), agouti-related peptide (AgRP) and proopiomelanocortin
      (POMC) following in vitro incubation. Hypothalamic tissue from 4- to 5-month-old
      lambs was obtained at slaughter and immediately incubated in culture media for 2
      h at 36  degrees C. Treatments included a control Dulbecco's modified Eagle
      medium (DMEM) containing 1 mm glucose or DMEM with the following additions: 10 mm
      glucose, 1 mm propionate, 1 nm insulin, 120 pm GLP-1, 100 pm PYY, 80 pm CCK or 10
      mm glucose plus 1 nm insulin. The abundance of mRNA for NPY, AgRP and POMC was
      measured using quantitative reverse transcriptase PCR. Fisher's protected LSD
      test was used to compare changes in relative mRNA concentrations for the
      hypothalamus incubated in the control media vs. the rest of the treatments. The
      media containing glucose plus insulin increased POMC mRNA concentration (p
      <0.05), but did not affect NPY or AgRP mRNA concentration. There were no effects
      observed for the other treatments (p > 0.20). Results of the present study are
      consistent with the concept that effects of propionate on feed intake in
      ruminants is not mediated through direct effects on the hypothalamus, and that
      insulin is required for an effect of glucose on hypothalamic POMC expression.

PMID- 21732995
TI  - Preferences of owners of overweight dogs when buying commercial pet food.
AB  - Most pet dogs in developed countries are fed commercial diets. The aim of this
      study was to evaluate the preferences of owners of overweight dogs when buying
      commercial pet food. The study was a descriptive observational multi-centre study
      on a group of 198 owners of urban household dogs. Personal interviews were
      conducted to examine the owners' opinions with questions rating the importance of
      certain qualities of prepared dog food. Bivariate analyses for comparisons of
      absolute means between groups of owners of dogs with excess weight (n = 137) and
      owners of normal weight dogs (n = 61) were made using the Mann-Whitney U-test. A
      low price (p < 0.001) and special offers (p = 0.008) of commercial dog food were
      more important for owners of dogs with excess weight than for owners of normal
      weight dogs. The quality of ingredients (p = 0.007) and the nutritional
      composition (p < 0.001) were more important for owners of normal weight dogs than
      for owners of dogs with excess weight. The veterinarian was the most important
      source of information on dog nutrition for both groups (83.6% for owners of
      normal weight dogs and 83.2% for owners of dogs with excess weight) (p = 0.88).
      The owners of dogs with excess weight had less interest in corrected dog
      nutrition than owners of normal weight dogs (p < 0.001).

PMID- 21732996
TI  - Co-ordination of quorum-sensing regulation in Rhizobium leguminosarum by
      induction of an anti-repressor.
AB  - Analysis of quorum-sensing (QS) regulation in Rhizobium leguminosarum revealed an
      unusual type of gene regulation that relies on the population density-dependent
      accumulation of an anti-repressor. The cinS gene, which is co-transcribed with
      the N-acyl-homoserine-lactone synthase gene cinI, is required to fully induce
      rhiR and raiR, whose products, together with their partner AHL synthases,
      regulate other genes in a QS-regulated hierarchy. Purified CinS bound to the R.
      leguminosarum transcriptional regulator PraR, which repressed rhiR and raiR
      expression. PraR bound to the rhiR and raiR promoters and CinS displaced PraR
      from these promoters, thereby inducing their expression. Although induction of
      cinS required CinI-made AHL, it appears CinS does not require the AHL for its
      anti-repressor function. The LuxR-type regulator ExpR was also required for
      normal induction of rhiR and raiR and it appears that this occurs by ExpR
      repressing the transcription of praR. Therefore ExpR and CinS act independently
      to attenuate PraR action, ExpR by repressing its transcription and CinS by
      attenuating its repressive activity. Thus, as CinS accumulates in a population
      density-dependent manner it induces the QS hierarchy by relieving PraR-mediated
      repression of rhiR and raiR.

PMID- 21732997
TI  - The male bias in the number of Purkinje cells and the size of the murine
      cerebellum may require Mullerian inhibiting substance/anti-Mullerian hormone.
AB  - There is a male bias in the size of the cerebellum, with males, on average,
      having more Purkinje cells than females. The critical periods in cerebellum
      development occur when the immature testes secrete Mullerian inhibiting substance
      (MIS; synonym anti-Mullerian hormone) but only trace levels of testosterone. This
      suggests that the male bias in the cerebellum is generated by a different
      mechanism to the testosterone-sensitive reproductive nuclei. Consistent with
      this, in the present study, we report that Purkinje cells and other cerebella
      neurones express receptors for MIS, and that MIS(-/-) male mice have female-like
      numbers of Purkinje cells and a female-like size to other parts of their
      cerebellum. The size of the cell bodies of Purkinje cells was also dimorphic,
      although only a minority of this was a result of MIS. This suggests that MIS
      induces the initial male bias in the cerebellum, which is then refined by
      pubescent testosterone and/or other sex-specific factors.

PMID- 21732998
TI  - External validation of exhaled breath profiling using an electronic nose in the
      discrimination of asthma with fixed airways obstruction and chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Fixed airflow limitation can be found both in asthma and chronic
      obstructive pulmonary disease (COPD), posing a day-to-day diagnostic challenge.
      OBJECTIVE: We aimed to determine the external validity of metabolomic analysis of
      exhaled air by electronic nose for distinguishing asthma and COPD in patients
      with fixed airways obstruction. METHODS: One hundred patients were included in a
      cross-sectional design: 60 asthma patients: 21 with fixed airways obstruction
      (fixed asthma), 39 with reversible airways obstruction (classic asthma) and 40
      COPD patients (GOLD stages II-III). Standardized sampling of exhaled breath was
      performed and volatile organic compounds were captured using an electronic nose
      resulting in breathprints. External validity in newly recruited patients
      (validation sets) was tested using a previous and independent training set.
      Breathprints were analysed by principal component and canonical discriminant
      analysis and area under the curve (AUC) of receiver operating characteristic
      curves. RESULTS: External validity of breathprints showed 88% accuracy for
      distinguishing fixed asthma from COPD (AUC 0.95, 95% CI 0.84-1.00, sensitivity
      85%, specificity 90%) and 83% for classic asthma (AUC 0.93, 95% CI 0.87-1.00,
      sensitivity 91%, specificity 90%) (both P<0.001). Discriminative accuracy was not
      confounded by current smoking. CONCLUSIONS AND CLINICAL RELEVANCE: External
      validation of exhaled breath molecular profiling shows high accuracy in
      distinguishing asthma and COPD in newly recruited patients with fixed airways
      obstruction. Exhaled air analysis may therefore reduce misdiagnosis in
      obstructive airways diseases, potentially leading to more appropriate management.

PMID- 21732999
TI  - Drug-specific cyclodextrins with emphasis on sugammadex, the neuromuscular
      blocker rocuronium and perioperative anaphylaxis: implications for drug allergy.
AB  - Cyclodextrins, oligosaccharides linked in a circular arrangement around a central
      cavity, are used extensively in the pharmaceutical industry to improve drug
      delivery. Their usefulness depends on their capacity to form a drug inclusion, or
      host-guest, complex within the cavity. In an attempt to improve the delivery of
      the widely used neuromuscular blocking drug (NMBD) rocuronium, a rocuronium
      inclusion complex was formed with a chemically modified gamma-cyclodextrin. The
      high binding affinity and specificity of the modified carrier (named sugammadex)
      for rocuronium (and other aminosteroid NMBDs) led to its use in anaesthesia as an
      innovative and useful agent for rapid reversal of rocuronium-induced
      neuromuscular block by sequestering the drug as an inclusion complex. This, in
      turn, led to the suggestion that sugammadex might be useful to remove the NMBD
      from the circulation of patients experiencing rocuronium-induced anaphylaxis, a
      suggestion subsequently supported in case reports where traditional treatment had
      failed. Successful resuscitations suggested that sugammadex might be a valuable
      new treatment for such intractable cases but, given the inappropriateness of
      clinical trials, confirmation or refutation will have to await the slow
      accumulation of results of individual case reports. Important questions related
      to antibody accessibility of drug allergenic structures on the rocuronium
      sugammadex inclusion complex, and the competition between sugammadex and IgE
      antibodies (both free and cell bound) for rocuronium, also remain and can be
      investigated in vitro. The sugammadex findings indicate that the use of carrier
      molecules such as the cyclodextrins to improve drug delivery will sometimes give
      rise to changed immunologic and allergenic behaviour of some drugs and this will
      have to be taken into account in preclinical drug safety assessments of drug
      carrier complexes. The possibility of encapsulating and removing other allergenic
      drugs, e.g., penicillins and cephalosporins, in cases of difficult-to-reverse
      anaphylaxis to these drugs is discussed.

PMID- 21733000
TI  - Diagnostic dilemmas of hyalinizing trabecular tumours on fine needle aspiration
      cytology: a study of seven cases with BRAF mutation analysis.
AB  - OBJECTIVE: Hyalinizing trabecular tumours (HTTs) are rare follicular-derived
      neoplasms that behave in an almost benign manner. HTT is frequently misdiagnosed
      as papillary carcinoma by fine needle aspiration (FNA) cytology or as papillary
      or medullary carcinoma on surgical resection. METHODS: The authors examined FNA
      material from seven cases of histologically verified HTT. Cytological findings
      were reviewed and correlated with ultrasonographic and histological features. In
      addition, MIB-1 and calcitonin immunostaining was performed on surgical
      specimens, and BRAF mutation analysis on three pre-operative FNA specimens and
      seven histology specimens. RESULTS: The original cytological diagnosis was either
      suspicious or positive for papillary carcinoma in all patients. The FNA-based
      differential diagnoses included HTT, papillary carcinoma or, less likely,
      medullary carcinoma in two patients. Aspirates showed oval to spindle-shaped
      cells with frequent intranuclear inclusions, isolated in loosely cohesive groups
      with a trabecular or syncytial pattern in a bloody background. Radiating
      arrangements of tumour cells surrounding hyaline stroma with serrated
      calcifications and a lack of papillary or sheet-like fragments may suggest HTT on
      FNA. Spherical calcified bodies and possible psammoma bodies were frequently
      found in three cases. Retrospectively, six of the seven cases showed membranous
      immunoreactivity for MIB-1, but none of the seven possessed the BRAF (V600E)
      mutation or showed calcitonin reactivity. CONCLUSIONS: Although the recognition
      of HTT on FNA cytology is difficult, because of its morphological similarities to
      papillary and medullary carcinoma, its characteristic cytological features along
      with ultrasonographic findings may suggest the diagnosis preoperatively and avoid
      surgical over-treatment.

PMID- 21733001
TI  - Cytological diagnosis of filarial infection in an endemic area where screening
      and prophylaxis is in place.
AB  - OBJECTIVE: Filariasis has a worldwide distribution. However, the disease is often
      overlooked or misdiagnosed because of its unusual presentations and there may be
      false-negative results in endemic areas. This study was carried out to assess the
      role of cytology in the demonstration of filarial parasites in an area where
      screening and prophylaxis are in place. METHODS: This study was carried out in
      Wardha district in central India, which is endemic for filarial infection. A
      total of 9182 smears of cases undergoing cytological evaluation were routinely
      screened at the time of reporting for the presence of adult filarial worm,
      microfilarial larvae or their fertilized and unfertilized eggs, irrespective of
      their original clinical diagnosis. RESULTS: Microfilariae were found incidentally
      in fine needle aspiration (FNA) smears of patients presenting with other clinical
      conditions. Smears of seven cases were found to be positive for microfilaria.
      Four cases presented with subcutaneous nodules in the upper arm, two cases were
      seen incidentally in axillary lymph node aspirates and microfilariae were found
      in the pleural fluid in one case. Another case was suspected to have breast
      cancer, but aspirates from the axillary area showed lymphatic obstruction
      considered to be due to filariasis. CONCLUSION: FNA cytology is an inexpensive,
      simple and easy procedure for detecting microfilariae. Detection of microfilariae
      may not be common even in endemic areas as screening and prophylaxis is routinely
      performed, and patients may show atypical presentations such as subcutaneous
      nodules. We believe that careful screening of FNAs, especially those from
      subcutaneous swellings, as well as serous fluids, is very important in a
      filariasis-endemic zone.

PMID- 21733002
TI  - Transfusion medicine--the way ahead.

PMID- 21733004
TI  - Thalassaemia: the long road from the bedside through the laboratory to the
      community.

PMID- 21733005
TI  - Transfusion tomorrow: Royal College of Pathologists, November 2010.

PMID- 21733007
TI  - Alcohol and cannabis abuse/dependence symptoms and life satisfaction in young
      adulthood.
AB  - INTRODUCTION AND AIMS: To examine the associations between substance
      abuse/dependence symptoms and life satisfaction, before and after adjustment for
      fixed and time-dynamic sources of confounding. DESIGN AND METHODS: Data were
      drawn from a 30year longitudinal study of a birth cohort of 987 individuals.
      Associations between alcohol abuse/dependence symptoms, cannabis abuse/dependence
      symptoms and life satisfaction were examined using repeated measures regression
      models. Associations were adjusted for fixed and time-dynamic sources of
      confounding, including family background, personality, demographics, recent life
      events, current employment and recent mental illness. RESULTS: There were
      significant associations between alcohol abuse/dependence and life satisfaction
      (P<0.0001) and between cannabis abuse/dependence and life satisfaction
      (P<0.0001). These significant associations remained after adjustment for fixed
      sources of confounding. However, adjusting for time-dynamic sources of
      confounding substantially reduced the associations. After adjustment for time
      dynamic sources of confounding there were no significant associations between
      alcohol abuse/dependence and life satisfaction (P>0.17) or cannabis
      abuse/dependence and life satisfaction (P>0.25). DISCUSSION AND CONCLUSIONS:
      These findings suggest that associations between life substance abuse/dependence
      and life satisfaction can be explained by time-dynamic factors, such as
      employment, life events and comorbid mental illness that are associated with
      reduced life satisfaction. When due allowance is made for confounding, alcohol
      and cannabis abuse/dependence are not associated with reduced life satisfaction.

PMID- 21733006
TI  - Consumption of clotting factors in severe haemophilia patients undergoing
      prophylaxis and on-demand treatment in Italy.

PMID- 21733008
TI  - Drugs, sex...and alcohol? Extending the community pharmacist's public health
      role.

PMID- 21733009
TI  - Credentialing of pharmacy technicians in the USA.
AB  - OBJECTIVE: This review will compare the USA and UK regarding pharmacy
      technicians' roles, it will summarize the current roles and responsibilities of
      pharmacy technicians in the USA, public perception of pharmacy technicians,
      pharmacy organizations' perspectives on pharmacy technician credentialing,
      academic programmes for pharmacy technicians, accreditation of pharmacy
      technician programmes, pharmacy technician certification exams and differing
      perspectives on the push for standardized technician training. It will conclude
      with observations regarding the importance of standardized pharmacy technician
      training. METHODS: Articles were identified via searches of PubMed and IPA from
      inception to November 2010 related to credentialing of pharmacy technicians.
      Search terms included pharmacy technician, pharmacy technician certification,
      pharmacy registration, technician education and technician requirements. Articles
      describing the roles and responsibilities of a technician, public perception of
      technicians, demographics, certification processes and the future of technician
      roles were included. An Internet search was also performed to identify articles
      in the lay press related to this topic. KEY FINDINGS: Providing a pharmacy
      technician with proper training and education is necessary for operating a
      successful pharmacy. In the USA, mandating a national standardized training
      programme is the source of the debate. Current rules and regulations regarding
      the training and education needed for a pharmacy technician vary from state to
      state in the USA. Attitudes of technicians towards standardized training may be
      difficult to change. CONCLUSION: This paper provides a review of pharmacy
      technicians' roles and responsibilities across different pharmacy settings.
      Although the literature provides some insight, more studies are needed to assess
      the value and impact of the knowledge and skills possessed by certified pharmacy
      technicians with standardized training compared with technicians with site
      specific or limited training.

PMID- 21733010
TI  - Can I help you? A qualitative study of pharmacist and pharmacy assistant views on
      the role of pharmacy assistants in New Zealand.
AB  - OBJECTIVES: To begin to explore the role of PAs more fully in a New Zealand
      context, through semi-structured interviews with PAs and pharmacists. METHODS:
      Semi-structured, qualitative interviews with a convenience sample of pairs of PAs
      and pharmacists working in a pharmacy together. KEY FINDINGS: Pharmacists and PAs
      both described important roles for PAs. The PAs tended to see themselves as the
      first point of contact for customers, and that they fulfilled an important
      healthcare role for the public. Pharmacists agreed that they were the first point
      of contact yet viewed this more as a gatekeeper role to the pharmacist. Views
      were also expressed about the difference between PAs and other retail employees.
      Pharmacists and PAs noted that the 'public' expected PAs to have a basic
      knowledge of non-prescription medicines and their uses. PAs described
      difficulties when requesting personal information from customers or asking
      essential questions where the customer had made a specific product request. Being
      able to know when to refer to the pharmacist was seen as a key role. CONCLUSION:
      Despite being able to describe a number of roles for PAs, these were highly
      variable. The lack of mandatory training and a clearly articulated role for PAs
      in New Zealand meant that in some cases PAs might be seen as little more than
      general retail assistants--a view not in line with their actual roles and
      practices. Attention to these issues may well help to resolve this, as will
      public education about the PA's role.

PMID- 21733011
TI  - Responsible self-medication: perceived risks and benefits of over-the-counter
      analgesic use.
AB  - OBJECTIVES: This study examines awareness of the potential risks associated with
      over-the-counter (OTC) use of paracetamol and non-steroidal anti-inflammatory
      drugs (NSAIDs) among Australian consumers to better understand patterns of usage
      of these products. METHODS: We employed two self-reported cross-sectional surveys
      (conducted in 2001 and 2009) using computer-aided telephone interviewing. Both
      survey samples were weighted to match national population proportions; data were
      collected for 3702 respondents (study 1, 2001, n=1901; study 2, 2009, n=1801).
      The inclusion criteria were age over 18 years and willingness to participate in
      the survey. KEY FINDINGS: Self-reported regular use (once or more per month) of
      OTC analgesics declined between 2001 (67.5%) and 2009 (55.0%; P<0.05). In 2009
      42.0% of regular OTC analgesic users were purchasing NSAIDs outside the pharmacy
      setting (compared with none in 2001). Stated awareness of potential risks has
      increased slightly among regular paracetamol users (from 49.0% in 2001 to 52.0%
      in 2009) and regular NSAID users (from 25.0% in 2001 to 41.0% in 2009). Regular
      OTC analgesic users were considered to be using the product appropriately if
      there were no contraindications, warnings, precautions or potential drug
      interactions to the analgesic that they had used. In 2001, significantly more
      people were using paracetamol appropriately than were using NSAIDs appropriately
      (98.3 compared with 79.3%; P<0.05). Corresponding figures for 2009 were 96.4 and
      69.1% (P<0.5). CONCLUSIONS: Increasing consumer awareness of the need to consider
      potential risks prior to taking OTC analgesics is a positive sign. However, this
      has not translated to an increase in appropriate use of OTC NSAIDs; since
      ibuprofen has become available outside the pharmacy setting in Australia fewer
      people are using NSAIDs appropriately according to the label. The quality use of
      medicines, in particular OTC NSAIDs, is becoming increasingly reliant on product
      labelling and the ability of consumers to understand and self-assess risk.

PMID- 21733012
TI  - A survey on the knowledge, beliefs and behaviour of a general adult population in
      Malaysia with respect to the adverse effects of medicines.
AB  - OBJECTIVE: The aim of the study was to explore, in the Malaysian general
      population: knowledge and beliefs of the characteristics in general of medication
      related side effects and side effects associated with different types of
      medicines; behaviour related to the safe use of drugs before and after taking a
      medication; and behaviour in the event of a medication-related side effect.
      METHODS: A 24-item self-administered questionnaire was developed and used to
      survey the general public living or working in suburban Kuala Lumpur, Malaysia.
      Eight hundred questionnaires were distributed, face to face, by researchers using
      quota sampling. Respondents' knowledge, belief and behaviour were analysed and
      correlated with demographics, medical history and experience of side effects. KEY
      FINDINGS: Six hundred and ten respondents completed the questionnaire giving a
      response rate of 76.3%. The mean knowledge score for the respondents was 18.4+/
      3.6 out of the maximum possible score of 26. Educational level and experience of
      side effect had an influence on the knowledge score obtained. Respondents had
      misconceptions regarding the safety of complementary and alternative medicines
      (CAMs) and over-the-counter medications. Medication history and previous
      experience with side effects had a significant influence on the higher behaviour
      score obtained. CONCLUSION: The survey has shown moderate results with regard to
      the knowledge of public regarding safety of medications, and there was evidence
      of under-estimating the risk of medications, especially CAMs. The misconceptions
      among the public, and inappropriate behaviour on drug safety-related aspects, is
      a concern which needs to be addressed in the interventions designed.

PMID- 21733013
TI  - Job satisfaction and the association with involvement in clinical activities
      among hospital pharmacists in Hong Kong.
AB  - OBJECTIVES: To describe the relationship between job satisfaction of hospital
      pharmacists and the extent of their involvement in clinical pharmacy activities,
      and to examine if demographics and practice characteristics are associated with
      the extent of involvement in clinical pharmacy activities and job satisfaction.
      METHODS: A cross-sectional study was conducted by surveying with a self
      administered questionnaire mailed to all full-time pharmacists employed by the
      Hospital Authority, Hong Kong. KEY FINDINGS: Respondents reporting job and career
      satisfaction averaged near the neutral point. The results indicated an unmet
      expectation of work balance between clinical activities and drug distribution,
      with the majority of responding pharmacists desiring a shift of work balance from
      more drug distributive roles towards more clinical activities. The results also
      suggested that an unmet expectation in work balance affects job and career
      satisfaction, particularly in younger, frontline pharmacists. CONCLUSIONS:
      Younger, frontline pharmacists reported lower job satisfaction and a greater gap
      of unmet expectations in their work balance. This study highlights the importance
      of pharmacists' involvement in clinical activities, as job enrichment would
      improve job satisfaction and maximise benefits towards patients and healthcare
      organisations.

PMID- 21733014
TI  - Measuring dispensary workload: a comparison of the event recording and direct
      time techniques.
AB  - OBJECTIVES: To compare dispensary workload, determined using the Welsh
      benchmarking event recording technique and the direct time technique, at two
      district general UK National Health Service hospitals within different university
      local health Boards (hospital A--manual dispensing system; hospital B--automated
      dispensing system). METHODS: Data on dispensary workload were collected, over a
      period of 6 weeks (hospital A: 8 May-18 June 2007; hospital B: 1 October-11
      November 2007), by a non-participant observer using two simultaneous methods of
      workload measurement: direct time and event recording. Direct time technique
      involved timing each task involved in dispensing a sample of prescriptions from
      receipt to issue of dispensed medicines to patients. Welsh benchmarking event
      recording involved continuously logging staff activities that deviated from the
      dispensary rota on a data collection form to enable calculation of total staff
      time involved in dispensing activities. Data on number of items dispensed were
      obtained from the pharmacy computer system and also by manual counting of
      prescription items. The mean dispensary workloads were calculated as the number
      of items dispensed per person per hour. Two-sample t-tests were used to compare
      dispensary workload measurements determined using direct time and event recording
      technique reported by each individual hospital. Mean workloads for hospitals A
      and B were compared using a two-sample t-test. Statistical significance was taken
      as P<=0.05. KEY FINDINGS: Hospital A was associated with a lower workload (direct
      time: 7.27+/-7.16 items per person per hour; event recording: 9.57+/-10.6 items
      per person per hour). In contrast, hospital B gave a higher workload (direct
      time: 11.93+/-8.3 items per person per hour; event recording: 12.6+/-8.80 items
      per person per hour). There was a significant difference between workload (direct
      time: P<0.01; event recording: P<0.01) reported for both hospitals. The direct
      time and event recording techniques produced consistent results at each hospital
      (hospital A: t=0.02, P=0.99; hospital B: t=0.004, P=0.1). CONCLUSION: The direct
      time and Welsh benchmarking event recording techniques produced consistent
      results at both hospitals. Thus the Welsh benchmarking event recording technique
      is a valid and reproducible method of measuring dispensary workload. Hospital B
      (automated) had a higher workload than hospital A (manual). Further work is
      required to investigate the impact of automation on dispensary workload.

PMID- 21733015
TI  - An evaluation of using multi-source feedback (MSF) among junior hospital
      pharmacists.
AB  - OBJECTIVE: The mini Peer Assessment Tool (mini-PAT) for pharmacists was
      introduced in 2006 as a formative method of assessing junior hospital pharmacists
      in the workplace and is the first widespread application of multi-source feedback
      (MSF) specifically within a pharmacy setting. The aim of this study was to
      evaluate the feasibility and measurement characteristics of the assessment
      method, in order to guide its future application. METHODS: At the time of the
      study (September 2008) the assessment had been in place for 3 years. All
      assessment data from the first 3 years were analysed retrospectively. KEY
      FINDINGS: We evaluated 633 mini-PAT assessments. Over the study period, the
      assessor response rate remained relatively consistent at 77% and compared
      favourably with applications of MSF within medicine. Members of the pharmacy team
      (pharmacists and pharmacy technicians) dominated the assessor nomination lists.
      It was encouraging to see completed assessment forms returned from nominated
      doctors and nurses with whom the junior pharmacist had been working. Differences
      were found between how different occupational groups rated the junior pharmacists
      against the 16 items on the assessment form (Kruskal-Wallis, df=3, P<0.001).
      Pharmacist assessors rated the junior pharmacists lowest against all 16 items on
      the mini-PAT assessment form, whereas nominated doctors rated them the highest.
      CONCLUSION: This study demonstrates that an MSF assessment method can
      successfully be applied to a wide range of junior hospital pharmacists, and that
      the majority of junior hospital pharmacists assessed meet expectations.

PMID- 21733016
TI  - Assessment of sotalol prescribing in a community hospital: opportunities for
      clinical pharmacist involvement.
AB  - OBJECTIVE: Due to risk of serious adverse drug events (ADEs) sotalol use is
      limited in renal insufficiency and heart failure. To reduce potential life
      threatening ADEs, medication safety initiatives that ensure appropriate dosing of
      sotalol are necessary. Pharmacist-managed renal dosing assessment programmes
      ensure appropriate dosing of renally eliminated medications. A prospective
      medication safety evaluation was conducted to assess the need to include sotalol
      in an existing renal dosing assessment programme as well as the impact of
      clinical pharmacist assessment on sotalol prescribing. METHODS: Patients in a 736
      bed community hospital, receiving sotalol during a 6-week period, were
      prospectively evaluated. Information was collected on indication, dosing,
      concomitant disease states and medications, renal function, QTc length, symptoms
      of toxicity and readmissions. Pharmacist recommendations were made when necessary
      and were followed to determine acceptance rate and patient outcomes. KEY
      FINDINGS: Thirty-six patients were prescribed sotalol for atrial
      tachyarrhythmias. Thirty-two (89%) were dosed inappropriately with respect to
      renal function. Twenty (56%) had left-ventricular dysfunction as defined by an
      ejection fraction of <= 40%. At time of initial assessment, 15 (42%) were
      exhibiting signs of potential sotalol toxicity. Pharmacists provided
      recommendations regarding discontinuation or dosage adjustment on 32 patients
      with a 38% full and a 12% partial acceptance rate. All-cause readmission rates
      for patients receiving appropriate therapy, including those after pharmacist
      recommendations were accepted (Group A; n=16), were compared to those remaining
      on inappropriate therapy (Group B; n=20). Readmission rates within 6 months
      differed between groups (31% for Group A, 55% for Group B; P=0.095, odds ratio
      3.7). CONCLUSION: This medication safety evaluation suggests the need for
      pharmacist assessment in patients receiving sotalol. Dosage adjustment or
      avoidance in patients with renal insufficiency, heart failure and other relative
      contraindications is often necessary to avoid toxicity. Sotalol was
      inappropriately prescribed in the majority of patients secondary to renal
      insufficiency. Based on this evaluation, it was recommended to add sotalol to the
      institution's pharmacist-managed renal dosing adjustment programme. Ensuring
      clinical pharmacist assessment when sotalol is prescribed can help reduce
      potential life-threatening ADEs and hospital readmissions.

PMID- 21733017
TI  - Pressure ulcer prevalence and prevention practices in care of the older person in
      the Republic of Ireland.
AB  - AIMS AND OBJECTIVES: The aim of this study was to establish pressure ulcer
      prevalence and prevention in the long-term care setting. BACKGROUND: There is no
      information on pressure ulcers prevalence in care of the older person in Ireland;
      therefore, a prevalence study was undertaken to investigate key aspects related
      to current practices in pressure ulcer prevention. DESIGN: A cross-sectional
      survey design was employed. METHOD: Ethical approval was received. Participants
      included 1100 older individuals residing in 12 long-term care settings. Data were
      collected using the Braden scale, the European Pressure Ulcer Advisory Panel
      minimum data set and pressure ulcer grading system. RESULTS: All participants
      were Irish and white, 70% were women, and 75% were aged 80 years or older.
      Prevalence was 9%, with 28% of pressure ulcers grade 1, 33% grade 2, 15% grade 3
      and 24% grade 4, mainly located on the sacrum (58%) and the heel (25%). Seventy
      seven per cent scored Braden low risk or not at risk; however, 53% were
      completely immobile/very limited mobility and 58% were chair/bedfast. There was a
      significant association between activity and mobility and pressure ulcer
      development (chi(2) = 45.50, p < 0.001 and chi(2) = 46.91, p = 0.0001,
      respectively). Fifty per cent had a pressure redistribution device in bed, and
      48% had one in use on the chair; however, 9% had a repositioning regime planned
      for when in bed and 5% planned for when seated in the chair. CONCLUSIONS: This
      paper reports on the first ever pressure ulcer prevalence survey conducted in
      long-term care in Ireland, and results provide significant insights into decision
      making and use of resources in the prevention of pressure ulcers. RELEVANCE TO
      CLINICAL PRACTICE: Pressure ulcers are common, costly and impact negatively on
      individuals. Current practices in prevention show several areas for improvement,
      namely, risk assessment, care planning and documentation.

PMID- 21733018
TI  - A narrative review of South Asian patients' experiences of cardiac
      rehabilitation.
AB  - AIMS AND OBJECTIVES: To review the empirical literature relating to South Asian
      patients' experiences of cardiac rehabilitation. BACKGROUND: Individuals of South
      Asian origin (originating from India, Pakistan, Bangladesh, or Sri Lanka) have
      increased risk of coronary heart disease-related mortality and morbidity. Low
      levels of cardiac rehabilitation participation have been reported among South
      Asian groups in several English-speaking countries. DESIGN: Narrative review.
      METHODS: Primary research evidence published in English between 1999-2010
      obtained using pre-defined search criteria in electronic databases MEDLINE,
      CINAHL, PubMed, EMBASE, Google Scholar and PsycINFO. RESULTS: Eleven studies met
      the inclusion criteria for review. Four prominent themes were identified in the
      literature related to: (1) exercise; (2) culture and religion; (3) programme
      access and structure; (4) communication and language. CONCLUSIONS: The emerging
      themes distilled from the review encompass several factors associated with South
      Asian patients' experiences of cardiac rehabilitation that are commensurate with
      low uptake and poor adherence. However, few researchers have disaggregated their
      data by ethnic origin to describe what might best meet the needs of South Asian
      patients. Further research is needed to thoughtfully address issues of uptake of
      and compliance with cardiac rehabilitation by South Asian patients and to support
      the development of culturally sensitive and safe CR programmes. RELEVANCE TO
      CLINICAL PRACTICE: The findings from this review can help nurses to develop
      guidelines for the design and delivery of culturally competent South Asian
      cardiac rehabilitation programmes. Important considerations related to physical
      exercise, language and communication preferences, religious and cultural needs
      and programme access and structure, need to be addressed in a culturally relevant
      and culturally sensitive manner to enhance the uptake and efficacy of cardiac
      rehabilitation for South Asian individuals.

PMID- 21733019
TI  - Correlation, causation, and agency.

PMID- 21733020
TI  - Are temporary staff associated with more severe emergency department medication
      errors?
AB  - The use of temporary staff in healthcare is on the rise due in part to work-force
      shortages and perceived cost savings. They may present an increased risk of
      errors from insufficient training and orientation, and less familiarity with
      local culture and practice. However, their impact, particularly in the emergency
      department where the risk of preventable medication errors is high, has not been
      established. The objective of this study was to evaluate whether temporary staff
      medication errors would be associated with more severe harm than permanent staff
      medication errors. We used a national Internet-based medication error reporting
      system (MEDMARX) and did a cross-sectional study of the dataset between the years
      2000 and 2005. After adjusting for clustering by facility, temporary staff errors
      were more likely than permanent staff errors to reach the patient (odds ratio
      [OR] 1.42, 95% confidence intervals [CI] 0.97-2.09), require patient monitoring
      (OR 1.91, 95% CI 1.21-3.03), result in temporary harm (OR 3.11, 95% CI 1.13
      8.59), and be life-threatening (OR 8.63, 95% CI 1.22-61.0). In conclusion,
      emergency department medication errors associated with temporary staff were more
      harmful than those associated with permanent staff.

PMID- 21733021
TI  - How do allied health professionals evaluate new models of care? What are we
      measuring and why?
AB  - The aim of this study was to identify what outcome measures or quality indicators
      are being used to evaluate advanced and new roles in nine allied health
      professions and whether the measures are evaluating outcomes of interest to the
      patient, the clinician, or the healthcare provider. A systematic search strategy
      was used. Medical and allied health databases were searched and relevant articles
      extracted. Relevant studies with at least 1 outcome measure were evaluated. A
      total of 106 articles were identified that described advanced roles, however,
      only 23 of these described an outcome measure in sufficient detail to be included
      for review. The majority of the reported measures fit into the economic and
      process categories. The most reported outcome related to patients was
      satisfaction surveys. Measures of patient health outcomes were infrequently
      reported. It is unclear from the studies evaluated whether new models of allied
      healthcare can be shown to be as safe and effective as traditional care for a
      given procedure. Outcome measures chosen to evaluate these services often reflect
      organizational need and not patient outcomes. Organizations need to ensure that
      high-quality performance measures are chosen to evaluate the success of new
      health service innovations. There needs to be a move away from in-house type
      surveys that add little or no valid evidence as to the effect of a new
      innovation. More importance needs to be placed on patient outcomes as a measure
      of the quality of allied health interventions.

PMID- 21733022
TI  - Heart failure patients receiving ACEIs/ARBs were less likely to be hospitalized
      or to use emergency care in the following year.
AB  - Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to decrease
      morbidity and mortality in heart failure (HF) patients in randomized-controlled
      trials; observational studies have confirmed this benefit among patients
      discharged with HF. Investigating the benefit of ACEIs or angiotensin receptor
      blockers (ARBs) among general HF patients has important implications for quality
      of-care measurement and quality initiatives. The objective of this study is to
      assess the impact of receipt of ACEIs/ARBs among patients with HF on
      hospitalization, emergency care, and healthcare cost during the following year.
      Using administrative data, we identified HF patients between 2000 and 2005 in a
      large health plan (n=2,396 patients). We conducted multivariate analysis to
      assess the impact of receipt of an ACEI/ARB on likelihood of hospitalization and
      emergency care, and on total healthcare cost. We found that patients who received
      ACEIs/ARBs were less likely to be hospitalized (odds ratio [OR]=0.82, p<.05) or
      use emergency care (OR=0.82, p<.05) in the following year. Receipt of ACEIs/ARBs
      was not associated with significantly increased cost. Incentivizing the receipt
      of ACEIs/ARBs in a general population with HF may be a suitable target for pay
      for-performance programs, disease management programs, or newer complementary
      frameworks, such as value-based insurance design.

PMID- 21733023
TI  - Putting a face on medical errors: a patient perspective.
AB  - Knowledge of the patient's perspective on medical error is limited. Research
      efforts have centered on how best to disclose error and how patients desire to
      have medical error disclosed. On the basis of a qualitative descriptive component
      of a mixed method study, a purposive sample of 30 community members told their
      stories of medical error. Their experiences focused on lack of communication,
      missed communication, or provider's poor interpersonal style of communication,
      greatly contrasting with the formal definition of error as failure to follow a
      set standard of care. For these participants, being a patient was more important
      than error or how an error is disclosed. The patient's understanding of error
      must be a key aspect of any quality improvement strategy.

PMID- 21733024
TI  - The relative effectiveness of managed care penetration and the healthcare safety
      net in reducing avoidable hospitalizations.
AB  - Avoidable hospitalizations represent a key indicator for access to, and the
      quality of, primary care. Therefore, understanding their behavior is essential in
      terms of management of healthcare resources and costs. This analysis examines the
      affect of 2 healthcare strategies on the rate of avoidable hospitalization,
      managed care and the healthcare safety net. The avoidable hospitalizations
      definition developed by Weissman et al. (1992) was used to identify relevant
      inpatient episodes. A 2-stage simultaneous equations multivariate regression
      model with instrumental variables was used to estimate the relative influence of
      HMO penetration and the composition of local hospital markets on the rate of
      avoidable hospitalizations. Control variables in the model include healthcare
      supply and demand, demographic, socioeconomic, and health status characteristics.
      Increased market presence of public hospitals significantly reduced avoidable
      hospitalizations. HMO penetration did not influence the rate of avoidable
      hospitalizations. The results suggest that public investments in healthcare
      facilities and infrastructure are more effective in reducing avoidable
      hospitalizations.

PMID- 21733025
TI  - Medicine administration errors and their severity in secondary care older
      persons' ward: a multi-centre observational study.
AB  - AIM AND OBJECTIVES: To assess the severity of medicine administration errors to
      older patients. BACKGROUND: Severity of medicine administration errors has been
      determined in a variety of settings but not in care-of-older-person wards, which
      this study aims to do. DESIGN: Undisguised observational study. PARTICIPANTS:
      Sixty-two nurses were observed administering oral medicines to 625 patients.
      INTERVENTIONS: Data were collected on the preparation and administration of oral
      medicines. Thirty-five cases of error were selected and analysed for their
      severity. RESULTS: In the 65 drug rounds observed 2129 potential drug
      administrations were made to 625 patients, of which 817 doses (38.4%) were given
      incorrectly (95% CI = 36.3-40.4). The overall mean harm score of the 35 incidents
      analysed was 4.1 (range 1.1-8.6, SD 1.8) on a scale of 0-10. CONCLUSIONS: The
      number and severity of MAEs observed is high compared with previous studies.
      RELEVANCE TO CLINICAL PRACTICE: There is a need to decrease the number and
      severity of MAEs, by increasing nurse awareness and error reporting.

PMID- 21733026
TI  - A prospective study of nosocomial urinary tract infection in hip fracture
      patients.
AB  - AIM: To investigate risk factors and consequences of nosocomial urinary tract
      infection in hip fracture patients. BACKGROUND: Nosocomial urinary tract
      infection is a well-known problem in hip fracture patients. There are several
      risk factors for nosocomial urinary tract infection described in the literature.
      DESIGN: Prospective observational study with a descriptive and comparative
      design. METHODS: Hip fracture patients were included consecutively between April
      2006-March 2007. Excluded were those under 50, having an indwelling urinary
      catheter, signs of cognitive impairment or additional severe physical problems at
      the time of admission. To verify nosocomial urinary tract infection, a urine
      specimen was taken at admission and discharge. Patients with and without
      nosocomial urinary tract infection were compared. RESULTS: The study included 86
      hip fracture patients, of whom 45 (52.3%) contracted nosocomial urinary tract
      infection in hospital. Earlier reported risk factors for nosocomial urinary tract
      infection were not confirmed in this study, with one exception: diabetes. All
      diabetic patients in the study contracted urinary tract infections. Patients
      receiving cloxacillin as antibiotic prophylaxis for wound infection contracted
      UTI less often than other patients. There were no statistical differences between
      groups with regard to urinary tract infection frequency four months after
      fracture or with regard to mortality after one year. CONCLUSION: Diabetes was the
      only previously known risk factor for nosocomial urinary tract infection
      confirmed among hip fracture patients in this study. Cloxacillin as antibiotic
      prophylaxis for surgery seemed to offer a certain protection against nosocomial
      urinary tract infection. RELEVANCE TO CLINICAL PRACTICE: Nurses in clinical
      practice should be aware of the risk of urinary tract infections in hip fracture
      patients and especially in hip fracture patients with diabetes. Patients given
      cloxacillin as antibiotic prophylaxis seem less likely to contract nosocomial
      urinary tract infection.

PMID- 21733027
TI  - Individual and work environment characteristics associated with error occurrences
      in Korean public hospitals.
AB  - AIMS: To determine individual and work environment characteristics associated
      with the occurrence of errors in Korean public hospitals. BACKGROUND: Medical
      errors are affected by individual and work environment characteristics. Few
      studies have examined the factors influencing medical errors, including
      perceptions of safety climate and individual and organisational characteristics.
      DESIGN: A survey. METHODS: A questionnaire was distributed to 2358 nurses in 33
      public hospitals to collect information on the frequency of errors, perceptions
      of safety climate and general characteristics of the participants. Data on
      hospital characteristics were obtained from the Regional Public Hospital Profile.
      The response rate was 89.7%. Multiple logistic regression analysis was performed
      to determine the factors influencing the occurrence of errors. RESULTS: Of the
      participants, 19% reported having made at least one error in the previous year.
      Nurses with better perceptions of workgroup- (OR = 0.73) and organisation- (OR =
      0.69) level safety climate were less likely to make errors. Nurses with less than
      3 years of nursing experience (OR = 2.05) were more likely to make errors than
      those with ten years or more. Nurses working at Red Cross hospitals (OR = 1.63)
      and in rural areas (OR = 2.04) were more likely to make errors than those at
      Regional Medical Centres and in urban areas, respectively. CONCLUSION: The
      factors associated with the occurrence of errors were perceived safety climate,
      years of nursing experience and hospitals' ownership and location. RELEVANCE TO
      CLINICAL PRACTICE: Public hospital executives and nurse managers should be
      actively involved in creating a strong safety climate. Furthermore, training
      programmes and managerial support focussed on improving patient safety and
      directed at less experienced nurses, especially those working at Red Cross
      hospitals in rural areas, need to be emphasised to prevent errors.

PMID- 21733028
TI  - Evidence of hidden biodiversity, ongoing speciation and diverse patterns of
      genetic structure in giant Antarctic amphipods.
AB  - Recent molecular research on Antarctic benthic organisms has challenged
      traditional taxonomic classifications, suggesting that our current perceptions of
      Antarctic biodiversity and species distributions must be thoroughly revised.
      Furthermore, genetic differentiation at the intraspecific level remains poorly
      understood, particularly in eastern Antarctica. We addressed these issues using
      DNA sequence data for two sibling amphipod species that could be collected on a
      circum-Antarctic scale: Eusirus perdentatus and Eusirus giganteus. Haplotype
      networks and Bayesian phylogenies based on mitochondrial (COI, CytB) and nuclear
      (ITS2) DNA provided strong evidence of multiple cryptic species of Eusirus, with
      several occurring in sympatry and at least one likely to have a true circum
      Antarctic distribution. Within species, gene flow was often highly restricted,
      consistent with a brooding life history and in some cases suggestive of current
      or future allopatric speciation. Patterns of genetic structure were not always
      predictable: one cryptic species showed preliminary evidence of high genetic
      differentiation across ~150 km in eastern Antarctica (F(ST) > 0.47, P < 0.01),
      yet another was remarkably homogenous across ~5000 km (F(ST) = 0.00, P = 1.00).
      Genetic diversity also varied among cryptic species, independent of sample size
      (pi = 0.00-0.99). These results indicate several hidden levels of genetic
      complexity in these Antarctic amphipods that are neither apparent from previous
      taxonomic or ecological studies nor predictable from their life history. Such
      genetic diversity and structure may reflect different modes of survival for
      Antarctic benthic organisms during historic glacial cycles, and/or subsequent re
      establishment of populations on the shelf, and highlight our misunderstanding of
      Antarctic marine species diversity.

PMID- 21733029
TI  - The impact of socioeconomic inequalities and lack of health insurance on physical
      functioning among middle-aged and older adults in the United States.
AB  - Socioeconomic inequalities and lack of private health insurance have been viewed
      as significant contributors to health disparities in the United States. However,
      few studies have examined their impact on physical functioning over time,
      especially in later life. The current study investigated the impact of
      socioeconomic inequalities and lack of private health insurance on individuals'
      growth trajectories in physical functioning, as measured by activities of daily
      living. Data from the Health and Retirement Study (1994-2006) were used for this
      study, 6519 black and white adults who provided in-depth information about
      health, socioeconomic, financial and health insurance information were analysed.
      Latent growth curve modelling was used to estimate the initial level of physical
      functioning and its rate of change over time. Results showed that higher level of
      income and assets and having private health insurance significantly predicted
      better physical functioning. In particular, decline in physical functioning was
      slower among those who had private health insurance. Interestingly, changes in
      economic status, such as decreases in income and assets, had a greater impact on
      women's physical functioning than on men's. Black adults did not suffer more
      rapid declines in physical functioning than white adults after controlling for
      socioeconomic status. The current longitudinal study suggested that anti-poverty
      and health insurance policies should be enhanced to reduce the negative impact of
      socioeconomic inequalities on physical functioning throughout an individual's
      life course.

PMID- 21733030
TI  - Two weeks of postsurgical therapy may be enough for high-risk cases of
      endocarditis caused by Streptococcus viridans or Streptococcus bovis.
AB  - The duration of antimicrobial therapy after surgery for infective endocarditis
      (IE) is controversial. A short course of postsurgical therapy is currently
      accepted only for patients with negative valve culture. We performed a
      retrospective (1994-2008) analysis of patients who underwent surgery for IE in
      our hospital and had a high risk of complications ( one of more of the following:
      <2 weeks of antibiotic treatment before surgery; embolism; perivalvular
      extension; and positive valve culture) to compare outcomes of patients who
      received short-course antimicrobial therapy (SAT) (median 15 days) or long-course
      antimicrobial therapy (LAT) (median 32 days), irrespective of the results of
      valve culture. Our endpoints included length of hospital stay, renal and hepatic
      failure, relapse, re-infection, and mortality rates 1 year after surgery. During
      the study period, 140 patients underwent surgery for IE (valve replacement,
      87.9%). Of these, 133 fulfilled the high-risk group criteria and 92 completed the
      antimicrobial schedule. Comparison of patients receiving SAT (37) and LAT (55)
      showed that the SAT group had a shorter length of hospital stay (29 vs. 40 days,
      p 0.01), and a trend towards lower frequency of renal failure (5.4% vs. 18.2%, p
      0.11) and hepatic failure (5.4% vs. 9.1%, p 0.69), whereas mortality (5.4% vs.
      3.6%, p 1), relapse (0% vs. 1.8%, p 1) and re-infection (5.4% vs. 3.6%, p 1)
      rates were similar between both groups. Multivariate analysis showed that IE
      caused by Streptococcus viridans or Streptococcus bovis was independently
      associated with SAT. Postsurgical SAT is safe, especially when IE is caused by
      Streptococcus viridans or Streptococcus bovis, even in patients at high risk of
      complications.

PMID- 21733031
TI  - Molecular epidemiology of late recurrent candidaemia--a population-based study in
      Iceland.
AB  - Candidaemia is associated with high patient mortality. Among those who survive an
      initial episode of candidaemia, the incidence of recurrent episodes has been
      incompletely defined. All patients in Iceland with candidaemia in 1980-2008 were
      identified, and clinical information was reviewed. Episodes of candidaemia in the
      same patient were considered to be separate if they occurred >= 1 month apart or
      were caused by different Candida species. The isolates were genotyped by using
      PCR fingerprinting, and antifungal susceptibility was determined. During the 29
      year period, candidaemia was diagnosed in 307 patients in Iceland, 298 of whom
      (97.1%) had a single episode. Overall, 206 patients survived >1 month from the
      first episode and were therefore at risk of recurrence, yielding 1062 patient
      years of observation in the survivors. Of those, nine (4.4%) later developed
      recurrent candidaemia. The median time between recurrences was 6 months (range,
      <1 month to 14 years). Patients with late recurrences were younger (p 0.012) and
      more likely to have underlying gastrointestinal diseases than patients with
      single episodes (55.6% vs. 18.5%, respectively; p 0.017). The recurrences were
      caused by identical Candida sp. genotypes in two of 13 cases (15%), but by
      different species or dissimilar genotypes in eight of 13 (62%); isolates were
      missing in three cases. In conclusion, late recurrent candidaemia was a
      relatively rare event, and younger patients with gastrointestinal disorders were
      more prone to recurrent infections. The majority of late recurrences represented
      re-infections with new Candida strains that were susceptible to common antifungal
      agents.

PMID- 21733032
TI  - Ultrasound assessment of endometrial cavity in perimenopausal women on oral
      progesterone for abnormal uterine bleeding: comparison of diagnostic accuracy of
      imaging with hysteroscopy-guided biopsy.
AB  - AIM: To investigate the effect of oral progesterone on the accuracy of imaging
      studies performed to detect endometrial pathology in comparison to hysteroscopy
      guided biopsy in perimenopausal women on progesterone treatment for abnormal
      uterine bleeding. METHODS: The study population comprised of women aged 40-55
      years with complaints of abnormal uterine bleeding who were also undergoing oral
      progesterone therapy. Women with a uterus >= 12 weeks' gestation size, previous
      abnormal endometrial biopsy, cervical lesion on speculum examination, abnormal
      Pap smear, active pelvic infection, adnexal mass on clinical examination or
      during ultrasound scan and a positive pregnancy test were excluded. A
      transvaginal ultrasound followed by saline infusion sonography were done. On the
      following day, a hysteroscopy followed by a guided biopsy of the endometrium or
      any endometrial lesion was performed. Comparison between the results of the
      imaging study with the hysteroscopy and guided biopsy was done. RESULTS: The
      final analysis included 83 patients. For detection of overall pathology, polyp
      and fibroid transvaginal ultrasound had a positive likelihood ratio of 1.65, 5.45
      and 5.4, respectively, and a negative likelihood ratio of 0.47, 0.6 and 0.43,
      respectively. For detection of overall pathology, polyp and fibroid saline
      infusion sonography had a positive likelihood ratio of 4.4, 5.35 and 11.8,
      respectively, and a negative likelihood ratio of 0.3, 0.2 and 0.15, respectively.
      CONCLUSION: In perimenopausal women on oral progesterone therapy for abnormal
      uterine bleeding, imaging studies cannot be considered as an accurate method for
      diagnosing endometrial pathology when compared to hysteroscopy and guided biopsy.

PMID- 21733033
TI  - Are serum markers altered in first trimester screening in poor ovarian reserve
      patients?
AB  - AIM: To investigate whether serum biochemical markers were altered during first
      trimester screenings in patients who have diminished ovarian reserve. METHODS:
      One hundred and fifty-one women who conceived after intracytoplasmic sperm
      injection were enrolled during the 11- to 14-week scan between June 2006 and July
      2008. The normoresponders (Group 1: 125 patients) had >6 oocytes and the poor
      responders (Group 2: 26 patients) had <=6 oocytes in oocyte retrieval. The means
      of the multiples of the median (MoM) of pregnancy-associated plasma protein A
      (PAPP-A), free beta-human chorionic gonadotropin (beta-hCG) and nuchal
      translucency of the poor responder and normoresponder groups were compared and a
      potential relationship between serum markers and poor ovarian reserve was
      investigated. Data were analyzed with the Student's t-test, chi2-test and Mann
      Whitney two sample test (unpaired, nonparametric). P < 0.05 was considered
      significant. RESULTS: The means of the MoMs of the poor responders and
      normoresponders were 1.16 +/- 0.45 and 1.04 +/- 0.32 (P = 0.111) for nuchal
      translucency, 0.92 +/- 0.48 and 0.89 +/- 0.61 (P = 0.399) for PAPP-A, and 1.08 +/
      0.40 and 1.21 +/- 0.95 (P = 0.831) for beta-hCG, respectively. CONCLUSION: There
      was no statistically significant difference between the groups in serum
      biochemical markers, nuchal translucency means and screen positive rates during
      the first trimester screening.

PMID- 21733034
TI  - Should lymphadenectomy be performed in early stage I and II sarcomas of the
      corpus uteri.
AB  - AIM: The aim of this study was to investigate the impact of radical
      lymphadenectomy as a prognostic factor in the management of uterine sarcomas.
      METHODS: Sixty patients with histologically-proven uterine sarcomas were
      recruited for this study. The patients were evaluated retrospectively, during the
      time period from September 1990 to June 2008, in the Department of Obstetrics and
      Gynecology of Aschaffenburg Clinic in Germany. The normality of the quantitative
      variables was tested using the Kolmogorov-Smirnov test. RESULTS: Of 60 patients,
      35 (58.3%) underwent total abdominal hysterectomy, bilateral salpingo
      oophorectomy and pelvic or para-aortic lymphadenectomy. The excision of iliac
      nodes was the strongest and most independent factor (beta = 0.64, P = 0.000)
      associated with survival. Recurrence of disease developed in 14 out of 25
      patients (56%) who did not receive lymphadenectomy, but in only 10 out of 35
      patients (29%) who underwent lymphadenectomy. The mean survival in years after
      surgery plus lymphadenectomy was 5.28 years, while in patients who did not
      undergo lymphadenectomy it was 1.56 years. CONCLUSIONS: Removal of lymphatic
      tissue in patients with early-stage uterine sarcoma significantly decreases the
      recurrence rate of the disease and improves the postoperative survival. However,
      there is a need for further prospective randomized controlled trials to
      investigate the adequate surgical management of uterine sarcomas and to clarify
      the prognostic value of lymphadenectomy at the initial surgery.

PMID- 21733035
TI  - Prepubertal vulval fibroma with a coincidental ectopic breast fibroadenoma:
      report of an unusual case with literature review.
AB  - Prepubertal vulval fibroma and ectopic breast fibroadenoma of the vulva are two
      rare tumors, and they are very difficult to distinguish from other vulval masses,
      both clinically and pathologically. The complication of the two diseases is
      extremely rare. We report the case of an extremely large and progressively
      enlarging mass in the vulva of an 18-year-old Chinese girl. The mass was excised
      completely and pathologically diagnosed as a prepubertal vulval fibroma and
      ectopic breast fibroadenoma. The patient was followed up for 10 months and no
      evidence of recurrence was observed. Prepubertal vulval fibroma and vulval
      ectopic breast fibroadenoma should be considered in their preoperative
      differential diagnosis of a vulval mass, especially in prepubertal girls.
      Pathologically, immunohistochemical staining for vimentin and CD34 is valuable
      for diagnosis. Complete surgical excision is effective and long-term follow up is
      necessary.

PMID- 21733036
TI  - Coexistence of endometriosis and uterine septum in patients with abortion or
      infertility.
AB  - AIM:  To investigate the coexistence of endometriosis and uterine septum patients
      whose complaints are abortion and infertility. METHODS: Ninety-two patients with
      a uterine septum and 191 patients who had undergone diagnostic laparoscopy for
      infertility were reviewed. The incidence of endometriosis in patients with a
      uterine septum was compared with patients with a normal uterine cavity; then the
      incidence of endometriosis was compared in association with having a preoperative
      diagnosis of presumed unexplained infertility in women with a partial or complete
      uterine septum. RESULTS: There was no significant difference between the patients
      who had a uterine septum and those with a normal cavity in terms of the incidence
      of endometriosis (P = 0.39). Also, the incidence of endometriosis was not
      significantly different in patients who had a complete or partial uterine septum
      (P = 0.49). Endometriosis was observed in 8.7% of the patients who were presumed
      to have unexplained infertility in the complete uterine septum group and in 18.8%
      of the patients in the partial uterine septum group; but the difference was not
      statistically significant when complete and partial uterine septum groups were
      compared according to the type of infertility (partial uterine septum group, P =
      0.13; complete uterine septum group, P = 0.28). CONCLUSION: An increased
      incidence of endometriosis was not observed in patients with a septate uterus.
      The reason for infertility in women with a partial uterine septum may be related
      to endometriosis.

PMID- 21733037
TI  - Influence of regular aerobic exercise on endothelium-dependent vasodilation and
      cardiorespiratory fitness in pregnant women.
AB  - AIM: To evaluate the effect of regular aerobic exercise on the endothelial
      function and cardiorespiratory fitness in pregnant women. METHOD: This was a
      randomized, double-blinded, controlled clinical trial of 64 healthy primigravid
      women between 16 and 20 weeks' gestation. The experimental group took part in
      aerobic exercise at an intensity of 50-65% of their maximum heart rate for 60
      min, three times a week for 16 weeks. The control group undertook their usual
      physical activity. The outcomes were the endothelial function evaluated by flow
      mediated dilatation and cardiorespiratory fitness evaluated by the maximum
      indirect oxygen consumption (VO2max) in a 6-min walk test. RESULTS: Initially, no
      differences were found between the groups in any of the variables. At the end of
      the intervention, the participants that performed exercise showed a higher
      cardiorespiratory fitness, measured by the walked distance in the 6-min walk test
      (P = 0.014) and by the VO2max (P = 0.014). Also, the exercise group showed a
      lower heart rate at rest and a higher flow-mediated dilatation than the control
      group (P = 0.02). CONCLUSIONS: Regular aerobic exercise improves endothelium
      dependent vasodilation in pregnancy. This intervention may be an early and
      effective alternative to strengthen the prevention of disorders associated to
      endothelial dysfunction.

PMID- 21733038
TI  - Short- and long-term outcomes in babies born after antenatal magnesium treatment.
AB  - AIM: To identify the prenatal events associated with adverse outcome in babies
      born at less than 32 weeks' gestation, including antenatal magnesium sulfate
      treatment. METHODS: A case-control study was performed to examine the effect of
      long-term tocolysis with MgSO4. Long-term neonatal and infantile adverse outcomes
      were defined as one of the following: intraventricular hemorrhage,
      periventricular leukomalacia, cerebral palsy and infantile death. RESULTS: Data
      were analyzed for 425 cases (236 who received magnesium sulfate and 189 control
      cases who did not). Perinatal deaths included 13 cases that had received
      magnesium (5.5%) and 17 control cases (9.0%). Long-term neonatal and infantile
      adverse outcomes were noted in 80 cases. The factor associated with an increased
      risk of combined adverse outcome after adjustment for confounding effects was the
      administration of corticosteroids (adjusted odds ratio [OR] 0.47, 95% confidence
      interval [CI] 0.27-0.81), but not magnesium sulfate (OR 0.82, 95% CI 0.48-1.40).
      In the subgroup that also received ritodrine (n = 315), magnesium sulfate was
      given to 195 cases. In this group, the factor associated with an increased risk
      of combined adverse outcome (n = 64) after adjustment for the confounding effects
      was also corticosteroids (adjusted OR 0.25, 95% CI 0.13-0.49), but magnesium
      sulfate was not associated with an increase in risk (OR 0.64, 95% CI 0.34-1.22).
      CONCLUSIONS: Long-term tocolysis with magnesium sulfate is not a significant
      factor related to the occurrence of neonatal and infantile adverse outcomes.
      Further study is needed to clarify the dose-response effect of magnesium sulfate.

PMID- 21733039
TI  - Prevalence of celiac disease in parents of preterm or low birthweight newborns.
AB  - AIM:  Celiac disease (CD) may present with atypical symptoms, including poor
      pregnancy outcomes, such as preterm and low birthweight (LBW) deliveries, thus we
      aimed to investigate the frequency of CD in mothers and fathers of preterm or LBW
      newborns. MATERIALS AND METHODS: In this study, 316 parents of 164 preterm or LBW
      newborns and 246 parents of 123 healthy newborns were included. CD was screened
      using tissue transglutaminase immunoglobulin A. Endoscopic duodenal biopsy was
      provided in the seropositive cases. RESULTS: Positive tissue transglutaminase
      immunoglobulin A was found in six (1.1%; 1/94) individuals (three mothers and
      three fathers); five were from the study group (1.6%; 1/63) and one was from the
      control group (0.4%; 1/246). CD prevalence in mothers, fathers and parents of
      preterm newborns was 1/57 (1.8%), 1/57 (1.8%) and 1/29 (3.5%), respectively. In
      the LBW group, seropositivity in fathers was 1/50 (2%) with no seropositive
      mothers. Biopsy-proven CD was found in 1/159 mothers (0.6%) and 1/79 fathers
      (1.3%). Mean birthweights of the newborns of seropositive mothers and fathers
      were 214 g (P < 0.05) and 320 g lower than those of seronegative ones,
      respectively. However, in logistic regression analysis it was found that
      seropositivity of mothers or fathers did not affect gestational age or
      birthweight of the newborns. CONCLUSION: Because the prevalence of CD in parents
      of preterm or LBW newborns is not statistically higher than the healthy
      population, routine CD screening in that group cannot be recommended at the time
      being. For more definite conclusions further studies are needed.

PMID- 21733040
TI  - Low-grade appendiceal mucinous neoplasm with disseminated peritoneal
      adenomucinosis involving the uterus, mimicking primary mucinous endometrial
      adenocarcinoma: a case report.
AB  - We present a patient with a low-grade appendiceal mucinous neoplasm, resulting in
      disseminated peritoneal adenomucinosis (pseudomyxoma peritonei) with uterine
      involvement, and mimicking primary mucinous endometrial adenocarcinoma. On
      immunohistochemistry, neoplastic glands were cytokeratin 7-negative and
      cytokeratin 20-positive, indicating a gastrointestinal origin rather than a
      primary ovarian mucinous neoplasm. A diagnosis of uterine metastasis of
      appendiceal origin was made, based on the constellation of clinicopathological
      findings, that is, preceding appendiceal neoplasm, peritoneal involvement,
      absence of coexisting prototypical endometrioid adenocarcinoma or endometrial
      hyperplasia. The patient underwent hysterectomy and there was no evidence of
      disease progression at the 12-month follow up. This suggested the indolent nature
      of this particular neoplasm, despite its advanced stage.

PMID- 21733041
TI  - Serum maternal hepcidin levels 3 days after delivery are higher compared to those
      measured at parturition.
AB  - AIM: Our aim was to investigate the levels of hepcidin at parturition and 3 days
      after delivery and to relate hepcidin levels to parameters of iron homeostasis.
      MATERIALS AND METHODS: We measured hepcidin levels with mass spectrometry in
      serum samples of 38 term pregnant women taken just prior to and 3 days after
      vaginal delivery (n = 23) or cesarean section (CS) (n = 15). Hepcidin levels were
      related to iron homeostasis parameters and interleukin (IL)-6 levels. Parameters
      measured before and after delivery were compared with the Wilcoxon test. RESULTS:
      Serum iron levels (median, interquartile range) decreased (14.3, 9.6-21.1 vs.
      8.9, 6.8-11.5 umol/L, P < 0.01), while hepcidin levels increased (2.73, 2.2-3.45
      vs. 10.62, 6.70-15.89 ug/L, P < 0.01) by the third day after parturition compared
      to those measured before delivery. IL-6 levels were comparable before and after
      delivery. No direct association between serum hepcidin and iron homeostasis
      parameters or IL-6 levels was found. CONCLUSIONS: Factors triggering hepcidin
      synthesis dominate 3 days after delivery. Studies are needed to assess the
      contribution of hepcidin to iron homeostasis during the periparturition period.

PMID- 21733042
TI  - Seroprevalence of Treponema Pallidum antibody among pregnant population of
      Bangladesh.
AB  - AIM: The aim of this study was to investigate the seroprevalence of antibody to
      Treponema pallidum among pregnant women and its association with age, sexual
      behavior and socioeconomic status. MATERIALS AND METHODS: In this cross-sectional
      study, 1266 sera were collected from pregnant women attending Bangabandhu Sheikh
      Mujib Medical University and Rajshahi, Khulna and Chittagong Medical College
      Hospitals between February 2007 and April 2008. From each hospital, samples were
      collected from about a quarter of the total recruited pregnant women. Sera were
      tested to identify the antibody to T. pallidum using Treponema pallidum
      hemagglutination at the Virology Department of Bangabandhu Sheikh Mujib Medical
      University. Logistic regression was used to explore potential risk factors for
      syphilis. RESULTS: Among 1250 sera tested (16 sera were discarded due to
      hemolysis), 37 (2.96%) were positive for T. pallidum antibody. Higher
      seropositivity was associated with couples with no formal education, low
      socioeconomic status (P = 0.006), marriage at or before 18 years of age (P =
      0.002), multiple marriages of the husband (P = 0.031) and sexual activity for
      more than 10 years (P = 0.007). Among these factors, low education level of
      women, early age of marriage and multiple marriages of the husband showed
      individual effects on high seropositivity to T. pallidum. CONCLUSIONS: The high
      seroprevalence of syphilis among pregnant women attending the antenatal clinics
      of these hospitals indicates the need for the incorporation of screening for
      syphilis in routine antenatal screening in Bangladesh. Improvement of education
      level in the female population, prevention of early marriage and preventing
      polygamy of husbands may play an important role in prevention of syphilis among
      women.

PMID- 21733043
TI  - Effects on in vitro fertilization-embryo transfer outcomes of vascular
      endothelial growth factor receptor-1, -2 and -3 in eutopic endometrial tissue of
      women with endometriosis.
AB  - AIM:  This study was performed to assess the expression levels of vascular
      endothelial growth factor receptor (VEGFR)-1, -2 and -3 mRNA in eutopic
      endometrial tissue and their effects on in vitro fertilization-embryo transfer
      (IVF-ET) outcomes in women with endometriosis. MATERIALS AND METHODS: Twenty
      women with endometriosis III or IV (study group) and 20 with tubal infertility
      only (control group) were evaluated. Controlled ovarian stimulation in all
      patients consisted of the long protocol using gonadotrophin-releasing hormone
      agonist. Prior to the administration of 0.1 mg triptorelin daily in the mid
      luteal phase of the preceding menstrual cycle, a biopsy specimen was taken from
      the endometrial cavity, and the expression levels of VEGFR-1, -2 and -3 mRNA were
      analyzed with real-time reverse transcription-polymerase chain reaction. RESULTS:
      There were no significant differences in the numbers of retrieved oocytes and
      mature oocytes, fertilization rate and clinical pregnancy rate between the study
      and control groups. However, the implantation rate was significantly lower in the
      study group (P < 0.05). The relative amounts of VEGFR-1, -2 and -3 mRNA were
      significantly higher in the study group than in the control group (P < 0.001
      each). The relative amounts of VEGFR-1 and -3 mRNA were significantly higher in
      the non-pregnant than in the pregnant subgroup of the study group (P < 0.01, P <
      0.05, respectively). CONCLUSIONS: Increased expression of VEGFR in the
      endometrium, especially VEGFR-1 and -3, may be related to the development of
      endometriosis and may reduce the receptivity of the endometrium.

PMID- 21733044
TI  - Inhibitory effect of soluble platelet-derived growth factor receptor beta on
      intraosseous growth of breast cancer cells in nude mice.
AB  - Bone metastasis is a frequent complication of advanced breast cancer. On the
      basis of functional and molecular evidence, signaling mediated by the binding of
      platelet-derived growth factor (PDGF)-BB and -DD to PDGF receptor beta
      (PDGFRbeta) is critical for the survival and growth of metastatic breast cancer
      cells within the bone microenvironment. In this study, we propose a new approach
      to blocking PDGFRbeta signaling using soluble PDGFRbeta (sPDGFRbeta) as a decoy
      receptor for PDGF-BB and -DD secreted from tumor cells and bone marrow stromal
      cells. A bone-seeking TNBCT/Bo cell line was established by in vivo selection
      from TNBCT human breast cancer cells, which are negative for estrogen receptor,
      progesterone receptor, and human epidermal growth factor receptor 2 protein
      expression. The TNBCT/Bo cells were transfected with a mammalian expression
      vector encoding the extracellular domain of PDGFRbeta. A stable transfectant
      (TNBCT/Bo-sPDGFRbeta) grew at a similar rate to that of control cells under
      normal culture conditions, although growth stimulation of human fibroblasts with
      PDGF-BB was neutralized by the culture medium from TNBCT/Bo-sPDGFRbeta cells.
      Intratibial injection of TNBCT/Bo-sPDGFRbeta cells into athymic nude mice
      resulted in a significant decrease in tumor incidence compared with control mice
      (P < 0.01). This attenuated growth correlated with decreased cancer cell
      proliferation, angiogenesis, and recruitment of stromal cells, and with an
      increase in the number of apoptotic cells. These findings suggest that sPDGFRbeta
      is useful for the treatment of breast cancer bone metastasis.

PMID- 21733045
TI  - Breakage of the nuclear envelope by an extending mitotic nucleus occurs during
      anaphase in Schizosaccharomyces japonicus.
AB  - During open mitosis in higher eukaryotic cells, the nuclear envelope completely
      breaks down and then mitotic chromosomes are exposed in the cytoplasm. By
      contrast, mitosis in lower eukaryotes, including fungi, proceeds with the nucleus
      enclosed in an intact nuclear envelope. The mechanism of mitosis has been studied
      extensively in yeast, a closed mitosis organism. Here, we describe a form of
      mitosis in which the nuclear envelope is torn by elongation of the nucleus in the
      fission yeast Schizosaccharomyces japonicus. The mitotic nucleus of Sz. japonicus
      adopted a fusiform shape in anaphase, and its following extension caused
      separation. Finally, a tear in the nuclear envelope occurred in late anaphase. At
      the same time, a polarized-biased localization of nuclear pores was seen in the
      fusiform-shaped nuclear envelope, suggesting a compromise in the mechanical
      integrity of the lipid membrane. It has been known that nuclear membrane remains
      intact in some metazoan mitosis. We found that a similar tear of the nuclear
      envelope was also observed in late mitosis of the Caenorhabditis elegans embryo.
      These findings provide insight into the diversity of mitosis and the biological
      significance of breakdown of the nuclear envelope.

PMID- 21733046
TI  - Improved retention rates with low-cost interventions in hypertension and diabetes
      management in a rural African environment of nurse-led care: a cluster-randomised
      trial.
AB  - OBJECTIVE: To compare the effects of low-level facility-based interventions on
      patient retention rates for cardiovascular (CV) disease in an environment of task
      shifting and nurse-led care in rural health districts in Central Cameroon.
      METHODS: This study is an open-label, three-arm, cluster-randomised trial in
      nurse-led facilities. All three groups implemented a treatment contract. The
      control group (group 1) had no additional intervention, group 2 received the
      incentive of 1 month of free treatment every forth month of regularly respected
      visits, and group 3 received reminder letters in case of a missed follow-up
      visit. The primary outcome was patient retention at 1 year. Secondary outcomes
      were adherence to follow-up visit schemes and changes in blood pressure (BP) and
      blood glucose levels. Patients' monthly spending for drugs and transport was
      calculated retrospectively. RESULTS: A total of 33 centres and 221 patients were
      included. After 1 year, 109 patients (49.3%) remained in the programme. Retention
      rates in groups 2 and 3 were 60% and 65%, respectively, against 29% in the
      control group. The differences between the intervention groups and the control
      group were significant (P < 0.001), but differences between the two intervention
      groups were not (P = 0.719). There were no significant differences in BP or
      fasting plasma glucose trends between retained patients in the study groups.
      Average monthly cost to patients for antihypertensive medication was ? 1.1 +/-
      0.9 and for diabetics ?1.2 +/- 1.1. Transport costs to the centres were on
      average ?1.1 +/- 1.0 for hypertensive patients and ?1.1 +/- 1.6 for patients with
      diabetes. CONCLUSIONS: Low-cost interventions suited to an environment of task
      shifting and nurse-led care and needing minimal additional resources can
      significantly improve retention rates in CV disease management in rural Africa.
      The combination of a treatment contract and reminder letters in case of missed
      appointments was an effective measure to retain patients in care.

PMID- 21733047
TI  - Hantavirus ecology in rodent populations in three protected areas of Argentina.
AB  - In this study, we identified hantavirus genotypes and their reservoirs and
      evaluated the spatial and temporal distribution of the virus in rodent population
      in three protected areas of Argentina over 3 years (2007-2010). A total of 837
      rodents were captured with an effort of 22 117 trap-nights. We detected the
      genotype Lechiguanas in Oligoryzomys nigripes and O. flavescens and Pergamino in
      Akodon azarae. There was no correlation between seroprevalence and trap success
      of the host. The proportion of seropositive males was significantly higher than
      the proportion of seropositive females. The total length of seropositives was
      higher than that of seronegatives in each host species. Seropositive individuals
      were observed in warm months and not in cold months, which suggests an infection
      cycle. This investigation confirms that protected areas of central east Argentina
      are places with a variety of sylvan rodents species associated with different
      hantavirus genotypes where reservoirs are numerically dominant. Although there
      was more than one known reservoir of hantavirus, only one species had antibodies
      in each area. This can be explained because the transmission of the virus does
      need not only the presence of a rodent species but also a threshold density.
      Longevity of even a small proportion of the host population in cold months may
      provide a trans-seasonal mechanism for virus persistence. The seroprevalence
      detected was higher than the one found before in rodent populations of Argentina,
      and this explains the appearance of human cases in two of these three areas.

PMID- 21733048
TI  - Can benign prostatic hyperplasia be identified in the primary care setting using
      only simple tests? Results of the Diagnosis IMprovement in PrimAry Care Trial.
AB  - AIMS: Diagnosis IMprovement in PrimAry Care Trial (D-IMPACT) was a prospective,
      multicentre epidemiological study in three European countries to identify the
      optimal subset of simple tests applied in primary care to diagnose benign
      prostatic hyperplasia (BPH) in men who spontaneously present with lower urinary
      tract symptoms (LUTS). METHODS: Consecutive male patients aged >= 50 years who
      spontaneously attended their regular general practitioner (GP) office with LUTS
      were eligible for inclusion if they had not previously undergone BPH diagnostic
      tests or received treatment for BPH. Patients were assessed on three occasions,
      twice by their regular GP (visits 1 and 2) and once by a urologist (visit 3). The
      diagnostic accuracy of each variable was determined using the urologists' final
      BPH diagnosis (at visit 3) as gold-standard. Independent variables analysed were
      as follows: age; BPH diagnosis performed by GP in visit 1 (yes/no); probability
      of BPH diagnosis assessed by GP in visit 1; urinalysis (normal/abnormal);
      prostate-specific antigen (PSA); International Prostate Symptom Score (IPSS);
      diagnosis of BPH performed by GP in visit 2 (yes/no); and probability of BPH
      diagnosis assessed by GP in visit 2. Statistically significant variables (p <
      0.1) were included in a logistic regression model to identify the best algorithm
      and describe each test contribution. RESULTS: The most frequent spontaneously
      reported LUTS were nocturia and weak urinary stream. BPH study prevalence was
      66.0% (95%CI: 62.3-69.5) and 32% of patients were at risk of BPH progression (PSA
      > 1.5 ng/ml and prostate volume >= 30 cm(3)). Among the independent variables
      analysed, only age, IPSS and PSA showed a statistically significant relationship
      with BPH diagnosis. In a logistic regression model including age, IPSS, PSA and
      probability of BPH (based on physical examination and symptoms), positive
      predictive value (PPV) was 77.1%. Exclusion of BPH probability resulted in a PPV
      of 75.7%. CONCLUSIONS: A diagnostic algorithm including only objective variables
      (age, IPSS and PSA), easily implemented in any GP office, allows GPs to
      accurately diagnose BPH in approximately three-quarters of patients spontaneously
      reporting LUTS.

PMID- 21733049
TI  - Lack of intra-laboratory reproducibility in using Platelia Aspergillus enzyme
      immunoassay test for detection of Aspergillus galactomannan antigen.

PMID- 21733050
TI  - Comparison of the clinical competence of nurses working in two university
      hospitals in Iran.
AB  - Hospitals are integrated with medical universities in Iran and are categorized
      into three types with respect to educational and health services quality. This
      cross-sectional study aimed to determine and compare the level of clinical
      competence of nurses who were working in type 1 and type 2 university hospitals.
      The clinical competence of all 266 nurses in the two hospitals was assessed by
      using the self-assessment method. The Nurse Competence Scale, a questionnaire
      consisting of 73 items, was used to assess the level of clinical competence and
      the frequency of using skills. The nurses who were working in the type 1
      university hospital viewed themselves as more competent than those who were
      working in the type 2 university hospital. Also, only 70% of the clinical skills
      were used frequently by the nurses who were working in the type 2 university
      hospital, in comparison to > 83% for the nurses who were working in the type 1
      university hospital. The results can be used for the educational needs assessment
      of nurses and for modifying the quality of care in hospitals.

PMID- 21733051
TI  - Prenatal alcohol consumption and knowledge about alcohol consumption and fetal
      alcohol syndrome in Korean women.
AB  - The study investigated prenatal alcohol consumption and knowledge of alcohol
      risks and fetal alcohol syndrome among Korean women. The participants were 221
      Korean women who attended the post-partum care centers in Seoul, Korea. The data
      included the participants' background characteristics, quantity-frequency
      typology, Student Alcohol Questionnaire, and a scale on the participants'
      knowledge of fetal alcohol syndrome. Alcohol was consumed during pregnancy by
      12.7% of the participants. Of these, 60.7% drank alcohol with their spouse. A few
      participants reported that nurses identified their drinking habits and gave them
      information on alcohol consumption and fetal alcohol syndrome. Most of the
      participants did not have the opportunity for prenatal counseling about fetal
      alcohol syndrome. The knowledge level regarding alcohol risks and fetal alcohol
      syndrome among the participants was poor. Alcohol consumption before pregnancy
      was significantly related to prenatal alcohol consumption. Prenatal alcohol
      consumption was not related to knowledge about alcohol consumption and fetal
      alcohol syndrome. The assessment of alcohol consumption and counseling about
      alcohol are needed for pregnant women in order to prevent fetal alcohol syndrome.

PMID- 21733052
TI  - Factors associated with depressive symptoms in low-income, older Korean women
      with hypertension.
AB  - The purpose of this study was to identify the factors that are associated with
      depressive symptoms in community-dwelling, low-income, older Korean women with
      hypertension. A total of 107 low-income, older (aged 74 +/- 6 years) Korean women
      with hypertension participated in the study. Information about depressive
      symptoms, functional status, and social support were collected by interviews that
      used the Geriatric Depression Scale, Katz's Activities of Daily Living, and the
      Lubben Social Support Network Scale, respectively. A logistic regression analysis
      was used to determine the factors that affected depressive symptoms. The results
      indicated that the depressed women had been diagnosed with hypertension for a
      longer period of time and took a larger number of medications than the women in
      the non-depressive group. They also had poorer functional status and an
      "isolated" social support network. The social support network, length of time
      since diagnosis, number of medications, and functional status were associated
      independently with depressive symptoms. It was concluded that clinicians should
      assess for the factors that are associated with depressive symptoms, including a
      poor social support network, poor daily activity, the number of medications, and
      the length of time since diagnosis in order to prevent the symptoms of
      comorbidities worsening in low-income, hypertensive, older women.

PMID- 21733053
TI  - Maternity care professionals' perceptions of supporting employed women in Norway.
AB  - The World Health Organization calls on health professionals to support women in
      combining maternity and work. The aim of this study was to explore midwives' and
      public health nurses' perceptions of supporting employed women to balance work
      and family life during pregnancy and early motherhood. An exploratory design,
      including multistage focus group interviews, was used. The focus group consisted
      of five midwives and one public health nurse who was working in maternity care.
      The data were analyzed by using qualitative content analysis. The comprehensive
      theme, "empowering the women when they are in 'another' state of normality", was
      based on two themes, "being in dialogue with the women" and "supporting the women
      to manage daily activities". The first theme was based on the subthemes,
      "perceiving the women to be in 'another' state of normality" and "providing an
      open atmosphere for dialogue", while the second subtheme was based on "confirming
      self-esteem" and "suggesting adjustments at work". The midwives and public health
      nurse empowered the women by enhancing their ability to carry out the self-care
      that was necessary in order to manage both their work and family life.
      Collaboration between maternity healthcare providers and employers should be
      developed in order to support employed women.

PMID- 21733054
TI  - Manual restraint and shows of force: the City-128 study.
AB  - Manual restraint is used to manage disturbed behaviour by patients. This study
      aimed to assess the relationship of manual restraint and show of force to
      conflict behaviours, the use of containment methods, service environment,
      physical environment, patient routines, staff characteristics, and staff group
      variables. Data from a multivariate, cross-sectional study of 136 acute
      psychiatric wards in England were used to conduct this analysis. Manual restraint
      was used less frequently on English acute psychiatric wards (0.20 incidents per
      day) than show of force (0.28 incidents per day). Both were strongly associated
      with the proportion of patients subject to legal detention, aggressive
      behaviours, and the enforcement of treatment and detention. Medical, nursing, and
      security guard staff provision were associated in different ways with variations
      in the use of these coercive interventions. An effective ward structure of rules
      and routines was associated with less dependence on these control methods.
      Training for manual restraint should incorporate the scenarios of attempted
      absconding and enforcement of treatment, as well as violent behaviour. Attempts
      to lessen usage of these interventions could usefully focus on increasing the
      availability of medical staff to patients, reducing reliance on security guards
      and establishing a good ward structure.

PMID- 21733055
TI  - Continuing challenges for the mental health consumer workforce: a role for mental
      health nurses?
AB  - The aim of this paper is to discuss issues impacting on consumer workforce
      participation and challenges that continue to arise for these workers, other
      service providers, and the mental health system. The literature identifies the
      following issues as problematic: role confusion and role strain; lack of support,
      training, and supervision structures; job titles that do not reflect actual work;
      poor and inconsistent pay; overwork; limited professional development;
      insufficient organizational adaptation to expedite consumer participation; staff
      discrimination and stigma; dual relationships; and the need to further evaluate
      consumer workforce contributions. These factors adversely impact on the emotional
      well-being of the consumer workforce and might deprive them of the support
      required for the consumer participation roles to impact on service delivery. The
      attitudes of mental health professionals have been identified as a significant
      obstacle to the enhancement of consumer participation and consumer workforce
      roles, particularly in public mental health services. A more comprehensive
      understanding of consumer workforce roles, their benefits, and the obstacles to
      their success should become integral to the education and training provided to
      the mental health nursing workforce of the future to contribute to the
      development of a more supportive working environment to facilitate the
      development of effective consumer roles.

PMID- 21733056
TI  - Remogliflozin etabonate, a selective inhibitor of the sodium-dependent
      transporter 2 reduces serum glucose in type 2 diabetes mellitus patients.
AB  - AIMS: Remogliflozin etabonate (RE) is the pro-drug of remogliflozin (R), a
      selective inhibitor of renal sodium-dependent glucose transporter 2 (SGLT2) that
      improves glucose control via enhanced urinary glucose excretion (UGE). This study
      evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of
      repeated doses of RE in subjects with type 2 diabetes mellitus (T2DM). METHODS:
      In a double-blinded, randomized, placebo-controlled trial, subjects who were drug
      naive or had metformin discontinued received RE [100 mg BID (n = 9), 1000 mg QD
      (n = 9), 1000 mg BID (n = 9)], or placebo (n = 8) for 12 days. Safety parameters
      were assessed, including urine studies to evaluate renal function. Plasma
      concentrations of RE and metabolites were measured with the first dose and at
      steady state. RE effects on glucose levels were assessed with fasting glucose
      concentrations, frequently sampled 24-h glucose profiles and oral glucose
      tolerance tests. RESULTS: No significant laboratory abnormalities or safety
      events were reported; the most frequent adverse events were headache and
      flatulence. Plasma exposure to RE and R were proportional to administered dose
      with negligible accumulation. Mean 24-h UGE increased in RE treatment groups.
      Compared with the placebo group, 24-h mean (95% CI) changes in plasma glucose
      were -1.2 (-2.2 to -0.3) (100 mg BID), -0.8 (-1.7 to 0.2) (1000 mg QD) and -1.7 (
      2.7 to -0.8) mmol/l (1000 mg BID). CONCLUSIONS: Administration of RE for 12 days
      is well-tolerated and results in clinically meaningful improvements in plasma
      glucose, accompanied by changes in body weight and blood pressure in subjects
      with T2DM.

PMID- 21733057
TI  - Does intentional weight loss reduce cancer risk?
AB  - Epidemiologic evidence points to obesity as a major risk factor for many cancers,
      including cancers of the breast, endometrium, colorectum, kidney, oesophagus and
      pancreas. Whether intentional weight loss might reduce this excess risk is not
      yet proven. We searched the medical literature for studies reporting changes in
      cancer risk following intentional weight loss, and for studies reporting changes
      in cancer-relevant risk factors of oestrogens, sex hormone binding globulin
      (SHBG), Insulin-like growth factor-I (IGF-I), IGF binding proteins and selected
      inflammatory markers [C-reactive protein (CRP), interleukin 6 (IL-6) and tumour
      necrosis factor-alpha (TNF-alpha)]. Observational cohort studies and randomized
      controlled trials of both dietary interventions and bariatric surgery all
      indicate fairly immediate reductions in cancer incidence following intentional
      weight loss. Oestrogen levels drop and SHBG levels increase coincident with
      intentional weight loss, with about a one-third reduction in free oestradiol to
      be expected from a 10% weight loss. CRP levels also drop substantially after
      weight loss at about this same 3 : 1 ratio. Reductions in TNF-alpha and IL-6 are
      consistently seen, but of a smaller magnitude, and IGF-I and IGFBP changes after
      weight loss are small and inconsistent. Because both cancer incidence and levels
      of circulating cancer biomarkers drop fairly rapidly following weight loss,
      intentional weight loss may well lead to meaningful reductions in cancer risk
      with a short latency time.

PMID- 21733058
TI  - Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and
      inadequate glycaemic control on metformin and pioglitazone: a 52-week,
      randomized, double-blind, active-controlled, parallel-group study.
AB  - AIM: To assess the efficacy and safety of adding alogliptin versus uptitrating
      pioglitazone in patients with type 2 diabetes and inadequate glycaemic control on
      metformin and pioglitazone. METHODS: In this randomized, double-blind, active
      controlled, parallel-group study, patients with type 2 diabetes and A1c >=7.0 and
      <=10.0% on metformin (>=1500 mg or maximum tolerated dose; Met) and pioglitazone
      30 mg (Pio30) received alogliptin 25 mg (Alo25; n = 404) or pioglitazone 15 mg (n
      = 399) added to Met+Pio30 for 52 weeks. The primary endpoint was change from
      baseline (CFB) in A1c at weeks 26 and 52, with sequential testing for non
      inferiority of Met+Pio30+Alo25 at weeks 26 and 52 and then for superiority at
      week 52. RESULTS: Met+Pio30+Alo25 showed superior glycaemic control versus
      Met+Pio45 at week 52 [least squares (LS) mean CFB in A1c, -0.70 vs. -0.29%; p <
      0.001]. At week 52, Met+Pio30+Alo25 resulted in greater CFB in A1c regardless of
      baseline A1c (p < 0.001); higher proportions of patients achieving A1c <=7.0
      (33.2 vs. 21.3%) and <=6.5% (8.7 vs. 4.3%; p < 0.001); greater CFB in fasting
      plasma glucose (FPG; LS mean CFB, -0.8 vs. -0.2 mmol/L; p < 0.001); and greater
      improvements in measures of beta-cell function (p < 0.001). Hypoglycaemia
      incidence was low (Met+Pio30+Alo25, 4.5%; Met+Pio45, 1.5%), mostly mild to
      moderate, but with two severe events in the Met+Pio30+Alo25 group. No meaningful
      differences in incidences of individual adverse events were observed between
      treatments. CONCLUSIONS: Adding alogliptin to an existing metformin-pioglitazone
      regimen provided superior glycaemic control and potentially improved beta-cell
      function versus uptitrating pioglitazone in patients with type 2 diabetes, with
      no clinically important differences in safety.

PMID- 21733059
TI  - Metformin opposes impaired AMPK and SIRT1 function and deleterious changes in
      core clock protein expression in white adipose tissue of genetically-obese db/db
      mice.
AB  - AIM: AMPK activates SIRT1 in liver and skeletal muscle. Impaired circadian
      function is associated with development of obesity. SIRT1 regulates circadian
      function and is suppressed in white adipose tissue (WAT) of obese patients. We
      examined the potential role of AMPK and SIRT1 in regulation of circadian
      components in WAT of obese db/db mice and in mice fed a high-fat diet (HFD), and
      investigated whether metformin-mediated activation of AMPK opposed any
      deleterious changes in the WAT clock mechanism. METHODS: db/+ and db/db mice were
      administered metformin (250 mg/kg/day; 7 days). Separately, mice were fed HFD for
      16-weeks. 3T3-L1 adipocytes were incubated with metformin, EX527 or FK866,
      inhibitors of SIRT1 and NAMPT, respectively. Gene and protein expression were
      measured by qRT-PCR and immunoblotting. RESULTS: AMPK activity, NAMPT expression
      and SIRT1 expression were decreased in WAT of db/db and HFD mice, in association
      with suppressed expression of the core circadian components CLOCK and BMAL1.
      Expression of Ppargamma and the adipogenic repressors Irf3 and Irf4 were also
      suppressed. Metformin increased AMPK activity in WAT of db/db mice and in
      metformin-treated adipocytes, with increased NAMPT, SIRT1 and circadian component
      expression. Metformin-mediated induction of Clock mRNA in adipocytes was blocked
      by inhibition of NAMPT and SIRT1. CONCLUSIONS: Decreased AMPK-SIRT1 signalling in
      db/db and HFD mice impacts WAT circadian function causing dysregulated lipid
      regulation, favouring an obese phenotype. Metformin mediates a phenotypic shift
      away from lipid accretion through AMPK-NAMPT-SIRT1 mediated changes in clock
      components, supporting chronotherapeutic treatment approaches for obesity.

PMID- 21733060
TI  - Glucoregulatory effects and prolonged duration of action of davalintide: a novel
      amylinomimetic peptide.
AB  - AIMS: Davalintide is a second-generation amylinomimetic peptide possessing
      enhanced pharmacological properties over rat amylin to reduce food intake in
      preclinical models. The current experiments in rats describe additional
      glucoregulatory actions of davalintide consistent with amylin agonism, and
      explore the duration of action of these effects. METHODS: Subcutaneous (SC)
      injection of davalintide slowed gastric emptying with equal potency to amylin
      (ED50's = 2.3 and 4.1 ug/kg). This effect was maintained for 8 h with
      davalintide, but not amylin. Intraperitoneal injection of davalintide also
      reduced food intake with a potency similar to amylin (ED50's = 5.0 and 11.3
      ug/kg). Consistent with amylin agonism, davalintide (10 ug/kg, SC) suppressed the
      plasma glucagon response over 90 min following an intravenous arginine bolus in
      anaesthetized rats. The elimination t(1/2) of davalintide (200 ug/kg, SC) was 26
      min, similar to the t(1/2) of amylin, suggesting that pharmacokinetic-independent
      mechanisms contribute to davalintide's enhanced duration of action. Binding
      kinetic studies using 125I davalintide revealed no appreciable dissociation from
      the amylin nucleus accumbens receptor after 7 h while 125I rat amylin did
      dissociate from this receptor (K(off) = 0.013/min). Sustained SC infusion of
      davalintide (275 ug/kg/day) or amylin (300) decreased plasma glucose after an
      oral glucose challenge at 2 weeks (by 27 and 31%) and suppressed gastric emptying
      at 3 weeks (by 29 and 47%), demonstrating durable glucoregulatory actions of both
      peptides. CONCLUSIONS: These data show glucoregulatory properties of davalintide
      consistent with amylin agonism and suggest that slowed receptor dissociation
      plays a role in davalintide's prolonged pharmacodynamic actions.

PMID- 21733061
TI  - Safety and efficacy of vildagliptin versus placebo in patients with type 2
      diabetes and moderate or severe renal impairment: a prospective 24-week
      randomized placebo-controlled trial.
AB  - AIM: Assess safety/tolerability and efficacy of the DPP-4 inhibitor vildagliptin
      in 515 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal
      impairment (RI). METHODS: Double-blind, randomized, parallel-group, placebo
      controlled, 24-week clinical trial assessing safety and efficacy of vildagliptin
      (50 mg qd) added to current antidiabetic therapy, in patients with T2DM and
      moderate or severe RI (GFR >= 30 to <50 or <30 ml/min/1.73 m(2) ). RESULTS: The
      study population comprised of 165 and 129 patients with moderate RI and 124 and
      97 patients with severe RI randomized to vildagliptin and placebo, respectively,
      with most patients receiving background insulin therapy (68 and 81% for moderate
      and severe RI, respectively). After 24 weeks, the between-treatment difference in
      the adjusted mean change in A1C was -0.5 +/- 0.1% (p < 0.0001) in moderate RI
      (baseline A1C = 7.9%) and -0.6 +/- 0.1% (p < 0.0001) in severe RI (baseline A1C =
      7.7%). In patients with moderate RI, similar proportions of those receiving
      vildagliptin or placebo experienced any AE (68 vs. 73%), any SAE (9 vs. 9%), any
      AE leading to discontinuation (3 vs. 5%) or death (1 vs. 1%). This was also true
      for patients with severe RI: AEs (73 vs. 74%), SAEs (19 vs. 21%), AEs leading to
      discontinuation (9 vs. 6%) and death (2 vs. 4%). CONCLUSIONS: In this 24-week
      study of 515 patients with T2DM and moderate or severe RI, vildagliptin added to
      ongoing antidiabetic therapy had a safety profile similar to placebo. Further,
      relative to placebo, vildagliptin elicited a statistically and clinically
      significant decrease in A1C in patients with moderate or severe RI.

PMID- 21733062
TI  - A review of orbital and intracranial magnetic resonance imaging in 79 canine and
      13 feline patients (2004-2010).
AB  - OBJECTIVE: To review the distribution of orbital and intracranial disease in
      canine and feline patients undergoing magnetic resonance imaging (MRI) following
      referral to a veterinary ophthalmologist and to correlate results of MRI with
      pathologic conditions including neoplasia, suspected optic neuritis (ON) and
      orbital cellulitis. Recognized and emerging imaging techniques are reviewed.
      PROCEDURE: Medical records of 79 canine and 13 feline patients were reviewed.
      RESULTS: Neoplasia was diagnosed in 53/92 (57.6%) of patients. The most prevalent
      types of neoplasia were carcinoma (16/53, 30.1%), sarcoma (11/53, 20.8%),
      lymphoma (8/53, 15.1%) and presumptive meningioma (9/53, 17.0%). Carcinomas and
      sarcomas were characterized by bony lysis and intracranial/sinonasal extension.
      Lymphoma was generally unilateral, less invasive and originated from the
      ventromedial orbit. Intracranial masses representing presumptive meningiomas
      frequently exhibited a 'dural tail' sign. Diagnosis of suspected ON was made in
      13 of 92 (14.1%) patients. Results of MRI in patients with suspected ON included
      unilateral optic nerve hyperintensity (3/13, 23.0%), bilateral optic nerve
      hyperintensity (1/13, 7.7%) and optic chiasmal hyperintensity (3/13, 23.0%).
      Seven suspected ON patients demonstrated intracranial multifocal patchy contrast
      enhancement (7/13, 53.8%). Diagnosis of orbital cellulitis was made in 12/92
      (13.0%) patients. CONCLUSIONS: Orbital neoplasia was the most common pathologic
      condition detected. Essential Roentgen characteristics are helpful when
      diagnosing pathologic processes and providing prognoses in cases of orbital or
      intracranial disease. Magnetic resonance imaging comprises an important
      diagnostic component in cases of suspected ON. Emerging contrast and functional
      MRI techniques as well as SI data may increase our ability to characterize
      disease processes.

PMID- 21733063
TI  - A slowly progressive retinopathy in the Shetland Sheepdog.
AB  - OBJECTIVE: To describe a slowly progressive retinopathy (SPR) in Shetland
      Sheepdogs. Animals  Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of
      SPR and six normal Shetland Sheepdogs were included in the study. PROCEDURE:
      Ophthalmic examination including slit-lamp biomicroscopy and ophthalmoscopy was
      performed in all dogs. Electroretinograms and obstacle course-test were performed
      in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups
      according to their dark-adapted b-wave amplitudes. SPR1-dogs had ophthalmoscopic
      signs of SPR, but normal dark-adapted b-wave amplitudes. Dogs with both
      ophthalmoscopic signs and subnormal, dark-adapted b-wave amplitudes were assigned
      to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination.
      RESULTS: The ophthalmoscopic changes included bilateral, symmetrical, greyish
      discoloration in the peripheral tapetal fundus with normal or marginally
      attenuated vessels. Repeated examination showed that the ophthalmoscopic changes
      slowly spread across the central parts of the tapetal fundus, but did not
      progress to obvious neuroretinal thinning presenting as tapetal hyper
      reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed
      significantly reduced b-wave amplitudes throughout dark-adaptation. Microscopy
      showed thinning of the outer nuclear layer and abnormal appearance of rod and
      cone outer segments. Testing for the progressive rod-cone degeneration ( prcd )
      mutation in three dogs with SPR was negative. CONCLUSION: Slowly progressive
      retinopathy is a generalized rod-cone degeneration that on ophthalmoscopy looks
      similar to early stages of progressive retinal atrophy. The ophthalmoscopic
      findings are slowly progressive without tapetal hyper-reflectivity. Visual
      impairment is not obvious and the electroretinogram is more subtly altered than
      in progressive retinal atrophy. The etiology remains unclear. SPR is not caused
      by the prcd-mutation.

PMID- 21733064
TI  - A survey of ocular abnormalities in miniature horses.
AB  - OBJECTIVE: To determine the incidence of ocular abnormalities in miniature
      horses. DESIGN: Descriptive study. ANIMALS STUDIED: Fifty-three miniature horses.
      PROCEDURE: Ophthalmic examinations were performed using diffuse and focal
      illumination, slit-lamp biomicroscopy and indirect ophthalmoscopy. Coat color,
      mane and tail color, age and gender were recorded with results of ophthalmic
      examination. RESULTS: Ocular abnormalities detected most frequently consisted of
      cysts arising from the posterior iris, ciliary body, and peripheral retina,
      curvilinear streaks of retinal pigmented epithelium extending from the peripheral
      temporal retina, and retinal dysplasia (folds). One miniature horse also had
      multiple ocular abnormalities (cornea globosa, goniosynechiae, decreased or
      absent and pupillary light reflexes, miotic and dyscoric pupils, iris hypoplasia,
      and epinuclear cataract). Ocular abnormalities were observed in horses that had a
      flaxen or white mane and tail color and a chocolate coat color. CONCLUSIONS:
      Abnormal ocular phenotype detected in eyes of Miniature Horses was similar to
      multiple congenital and hereditary ocular abnormalities reported in the Rocky
      Mountain Horse. Phenotypic ocular developmental abnormalities and coat, mane and
      tail color were most compatible with a heterozygous or homozygous effect of the
      Silver Dapple locus.

PMID- 21733065
TI  - Neuromuscular blockade with rocuronium bromide for ophthalmic surgery in horses.
AB  - PURPOSE: The production of a central eye to ease surgical access for intraocular
      surgery is generally dependent on the depth of anesthesia. The aim of this study
      was to evaluate the eyeball position under muscle relaxation with rocuronium
      during general anesthesia. MATERIAL AND METHODS: Twenty horses, body weight 480
      +/- 62 kg; age 12.6 +/- 6.2 years (mean +/- SD) were anesthetised for various
      ophthalmic surgeries. Horses were premedicated with acepromazine, xylazine, and
      butorphanol intravenously and anesthesia induced with ketamine and diazepam.
      Anesthesia was maintained with isoflurane in 100% oxygen and 0.6 mL/kg/h of an
      infusion containing midazolam, ketamine, and xylazine diluted in 500 mL 0.9%
      NaCl. Horses were mechanically ventilated. Neuromuscular function was assessed
      with an acceleromyograph (TOF-Guard(r)) and the N. peroneus superficialis was
      stimulated every 15 s with a train-of-four stimulation pattern. A dose of 0.3
      mg/kg rocuronium was administered intravenously. The changes in the eyeball
      position were recorded. RESULTS: The dose of 0.3 mg/kg rocuronium produced a 100%
      neuromuscular block in all horses. Onset time and clinical duration of block was
      2.38 +/- 2.02 min (range 0.5-8) and 32 +/- 18.6 min (range 7.7-76.2),
      respectively. The globe rotated to central position within 31 +/- 2.8 s. The
      whole iris was visible after 42 +/- 7.7 s in all horses. No additional bolus of
      rocuronium was necessary for any surgery. CONCLUSION: Neuromuscular blockade with
      rocuronium bromide can be used safely to facilitate ophthalmic surgery in
      equines.

PMID- 21733066
TI  - Allergic conjunctivitis and conjunctival provocation tests in atopic dogs.
AB  - INTRODUCTION: Canine atopic dermatitis (cAD) is a very common disease, but little
      is known about eye involvement. The conjunctival provocation test (CPT) is used
      in human to study the ocular response to allergenic stimuli and to evaluate anti
      allergic therapy. To our knowledge it has not been used in dogs. OBJECTIVES: To
      evaluate the prevalence of ocular signs in a population of atopic dogs and relate
      these with clinical cAD scores; and the usefulness of CPT for dust mites in
      atopic dogs with itchy eyes. PROCEDURES: Sixty cAD patients were evaluated for
      (i) ocular signs of allergic conjunctivitis including conjunctival hyperemia,
      chemosis, epiphora, ocular discharge, pruritus and corneal involvement, graded 0
      to 3 according to severity, and (2) cAD Extent and Severity Index (CADESI-03).
      Additionally, CPTs for Dermatophagoides farinae (n = 12) and Dermatophagoides
      pteronyssinus (n = 12) were performed in sensitized atopic dogs and 24 control
      dogs. RESULTS: Periocular and ocular signs of allergy were present in 60% (36/60)
      of cases. Conjunctival hyperemia (90%) was the most common sign. Severity of
      ocular signs was significantly correlated with eye pruritus (r(s)  = 0.690, P =
      <0.001) and skin lesions score for head region (r(s) = 0.261, P = 0.04). A highly
      significant difference (P < 0.001, Fisher test) was found in CPTs between the
      test and the control groups. CONCLUSION:  Allergic conjunctivitis signs
      associated with cAD seem under valuated so these patients would benefit from an
      ophthalmologic evaluation. Furthermore, we found CPT to be a reliable, easy to
      perform and safe test for the etiologic diagnosis of allergic conjunctivitis in
      the dog.

PMID- 21733067
TI  - In vivo measurement of central corneal thickness in normal chicks (Gallus gallus
      domesticus) with the optical low-coherence reflectometer.
AB  - OBJECTIVE: To determine the practicability and accuracy of central corneal
      thickness (CCT) measurements in living chicks utilizing a noncontact, high-speed
      optical low-coherence reflectometer (OLCR) mounted on a slit lamp. ANIMALS
      STUDIED:  Twelve male chicks (Gallus gallus domesticus). Procedures  Measurements
      of CCT were obtained in triplicate in 24 eyes of twelve 1-day-old anaesthetized
      chicks using OLCR. Every single measurement taken by OLCR consisted of the
      average result of 20 scans obtained within seconds. Additionally, corneal
      thickness was determined histologically after immersion fixation in Karnovsky's
      solution alone (20 eyes) or with a previous injection of the fixative into the
      anterior chamber before enucleation (4 eyes). RESULTS:  Central corneal thickness
      measurements using OLCR in 1-day-old living chicks provide a rapid and feasible
      examination technique. Mean CCT measured with OLCR (189.7 +/- 3.34 MUm) was
      significantly lower than histological measurements (242.1 +/- 47.27 MUm) in eyes
      with fixation in Karnovsky's solution (P = 0.0005). In eyes with additional
      injection of Karnovsky's fixative into the anterior chamber, mean histologically
      determined CCT was 195.2 +/- 8.25 MUm vs. 191.9 +/- 8.90 MUm with OLCR. A trend
      for a lower variance was found compared to the eyes that had only been immersion
      fixed. CONCLUSION: Optical low-coherence reflectometry is an accurate examination
      technique to measure in vivo CCT in the eye of newborn chicks. The knowledge of
      the thickness of the chick cornea and the ability to obtain noninvasive,
      noncontact measurements of CCT in the living animal may be of interest for
      research and development of eye diseases in chick models.

PMID- 21733068
TI  - Cryptococcus gattii chorioretinitis in a ferret.
AB  - Bilateral exudative chorioretinitis was diagnosed in an 18-month-old male
      neutered ferret (Mustela putorius furo) with a generalized Cryptococcus gattii
      infection confirmed by PCR. The animal was referred to the Ophthalmology Service
      of the Autonomous University of Barcelona (VTH-UAB) for acute onset blindness.
      Complete ophthalmic examination revealed absent menace response and dazzle reflex
      in both eyes (OU), as well as subretinal edema located in the tapetal fundus. At
      that time, the clinical ophthalmologic diagnosis was bilateral exudative
      chorioretinitis. Treatment with prednisone (0.5 mg/kg PO q24 h) was instituted in
      addition to the ongoing treatment with fluconazole (10 mg/kg PO q24 h). The
      following rechecks revealed secondary cataracts with subsequent lens subluxation
      and panretinal degeneration OU. Despite being blind and the poor prognosis of
      disseminate cryptococcosis, the patient remained active and in good body
      condition during 6 months after the initial diagnosis. At that time, the ferret
      showed ataxia, incontinence, and generalized pain. A magnetic resonance imaging
      study revealed a mass affecting the spine. The owners declined further
      investigations and the ferret was humanely euthanized. The postmortem
      histopathology confirmed the initial diagnosis of cryptococcosis and the presence
      of intraretinal Cryptococcus spp. To the authors' knowledge, this is the first
      report of Cryptococcus spp. induced exudative chorioretinitis in a ferret.

PMID- 21733069
TI  - Mortierella wolfii keratomycosis in a horse.
AB  - PURPOSE: To describe a case of superficial keratomycosis caused by Mortierella
      wolfii (M. wolfii) in a horse. METHODS: A thoroughbred filly was presented with
      painful right eye of 2 days' duration. A superficial corneal ulcer was observed
      ventrally together with multifocal punctuate opacities axially. Samples were
      collected by swabbing and scraping the ulcerated lesion and submitted for
      microbiologic and cytologic examination. RESULTS: Microscopic evaluation of
      debrided corneal tissue revealed the presence of nonseptate fungal hyphae, and
      culture of a corneal swab yielded fungal growth. Medical treatment with topical
      antifungal, antibiotic and autogenous serum and systemic anti-inflammatory
      resolved the problem within 2 weeks. CONCLUSIONS: Cytologic evaluation of a
      corneal scraping was useful to make a clinical diagnosis of keratomycosis. Based
      on the mycological characteristics, the fungus isolated from the corneal lesion
      was identified as M. wolfii. To the authors' knowledge, this is the first case
      report of equine keratomycosis associated with this fungus, although the organism
      is known to infect various organs of cattle.

PMID- 21733070
TI  - Repair of a scleral defect with an autogenous fascia lata graft in a dog.
AB  - A case of a traumatic scleral rupture with uveal herniation in a dog was treated
      with an autogenous fascia lata graft. Placement of the graft resolved the uveal
      prolapse and resulted in return of strength and a more normal structure. Fascia
      lata appears to be an effective scaffolding graft for the repair of scleral
      defects. It is cheap, easily harvested and large grafts may be obtained. Healing
      was rapid and the end result was a cosmetic, comfortable, fully functional eye.

PMID- 21733072
TI  - Propagation characteristics of the electrical impulse in the normal and
      obstructed ureter as determined at high electrophysiological resolution.

PMID- 21733073
TI  - Defining predictors of response to intralesional verapamil injection therapy for
      Peyronie's disease.
AB  - OBJECTIVE: * To assess factors that predict penile curvature responses to
      intralesional verapamil (ILV) injection therapy for men with Peyronie's disease
      (PD). PATIENTS AND METHODS: * Men with PD for <1 year were assessed at baseline
      and after 3 months of bi-monthly ILV-injection therapy. Curvature was assessed at
      the time of maximum penile rigidity. * Univariate relationships were tested with
      correlation or chi-square analyses. * Multivariate analyses included logistic and
      linear regression. * We analysed curvature improvement, defined as a decrease of
      >=10  degrees  from baseline. Additionally, the relationship between curvature
      outcomes and patient age and degree of baseline penile curvature were assessed.
      RESULTS: * Data from 131 men were included and the rates of penile curvature
      change were:26% improved, 12% worsened, and 62% stable. * Age (r=-0.24, P < 0.01)
      and larger baseline penile curvature (r= 0.33, P < 0.01) were associated with
      improved curvature on univariate analysis. * On multivariate analysis (logistic
      regression), both age [odds ratio (OR) 0.93, P < 0.01, 95%CI 0.89-0.97] and
      larger baseline penile curvature (OR 1.07, P < 0.01, 95%CI 1.04-1.11) were
      associated with improvements in curvature after ILV-injection therapy. *
      Improvements in curvature were associated with age (<=40 years vs >40 years; OR
      0.27, P < 0.05, 95%CI 0.10-0.75) and degree of penile curvature at baseline (<=30
      degrees  vs >30  degrees ; OR 9.12, P < 0.01, 95%CI 1.94-42.84) when
      dichotomized as indicated. CONCLUSION: * Younger age and larger baseline penile
      curvature were predictive of favourable curvature outcomes. * Analysis of
      dichotomized variables suggests that age and baseline curvature thresholds may be
      important to consider when deciding on ILV as a therapeutic strategy for PD.

PMID- 21733074
TI  - Erectile dysfunction is predictive of all-cause mortality in patients with
      prostate cancer treated with permanent interstitial brachytherapy.
AB  - OBJECTIVE: To evaluate the relationship between pre-treatment erectile function
      and all-cause mortality in patients with prostate cancer treated with
      brachytherapy. PATIENTS AND METHODS: In all, 1279 consecutive patients with
      clinically localized prostate cancer and pre-implant erectile function assessed
      by the International Index of Erectile Function-6 (IIEF-6) underwent
      brachytherapy. Potency was defined as an IIEF-6 score of >=13 without
      pharmacological or mechanical support. Patients were stratified into IIEF-6-score
      cohorts (<=12, 13-23 and 24-30). The median follow-up was 5.0 years. RESULTS: The
      8-year overall survival (OS) of the study population was 85.1%. The 8-year OS for
      IIEF-6scores <=12, 13-23 and 24-30 were 78.0%, 92.8% and 91.4%, respectively (P <
      0.001). Cardiovascular events accounted for a significant portion of deaths in
      each IIEF-6 group. When combined with other risk factors for cardiovascular
      disease, an IIEF-6 score of <=12 had an additive effect on all-cause mortality
      (IIEF-6 score of <=12 and less than two comorbidities vs two or more
      comorbidities were 18.2% and 32.1%). CONCLUSIONS: A pre-implant IIEF-6score of
      <=12 was associated with a higher incidence of all-cause mortality. Pre-treatment
      erectile dysfunction is a surrogate for underlying vascular pathology, probably
      explaining the lower OS in this subset of patients. Aggressive treatment of
      medical co-morbidity is warranted to impactOS.

PMID- 21733075
TI  - A systems-based modelling approach using transurethral resection of the prostate
      (TURP) specimens yielded incremental prognostic significance to Gleason when
      predicting long-term outcome in men with localized prostate cancer.
AB  - OBJECTIVE: To develop a systems-based model for predicting prostate cancer
      specific survival (PCSS) using a conservatively managed cohort with clinically
      localized prostate cancer and long-term follow-up. PATIENTS AND METHODS:
      Transurethral prostate (TURP) specimens in tissue microarray format and medical
      records from a 758 patient cohort were obtained. Slides were stained with
      haematoxylin and eosin (H&E), imaged and digitally outlined for invasive tumour.
      Additional sections were analysed with two multiplex quantitative
      immunofluorescence (IF) assays for cytokeratin-18 (epithelial cells), 4'-6
      diamidino-2-phenylindole(nuclei), p63/high-molecular-weight keratin (basal
      cells), androgen receptor (AR) and alpha-methyl CoA-racemase, Ki67,
      phosphorylated AKT (pAKT)and CD34. Images were acquired with spectral imaging
      software. H&E and IF images were evaluated with image analysis algorithms;
      feature data were integrated with clinical variables to construct prognostic
      models for outcome. RESULTS: Using a training set of 256 patients with 24%
      events, one clinical variable (Gleason score) and two tissue-specific
      characteristics (H&E morphometry and tumour-specific pAKT levels) were identified
      (concordance index [CoI] 0.79, sensitivity 76%, specificity 86%, hazard ratio
      [HR] 6.6) for predicting PCSS. Validation on an independent cohort of 269
      patients with 29% events yielded a CoI of 0.76, sensitivity 59%, specificity 80%
      and HR of 3.6. Both H&E and IF features were selected in a multivariate setting
      and added incremental prognostic value to the Gleason score alone (CoI 0.77 to
      CoI 0.79). Furthermore, global Ki67 expression and AR levels in Gleason grade 3
      tumours were both univariately associated with outcome; however, neither was
      selected in the final model. CONCLUSION: A previously validated prostate needle
      biopsy systems modelling approach that integrates clinical data with reproducible
      methods to assess H&E morphometry and biomarker expression, provided incremental
      benefit to the TURP Gleason score for predicting PCSS. Ki67 and AR, known to be
      associated with outcome in the prostate needle biopsy, were not associated with
      PCSS in multivariate models using TURP specimens.

PMID- 21733076
TI  - Effects of intravesical onabotulinumtoxinA on bladder dysfunction and autonomic
      dysreflexia after spinal cord injury: role of nerve growth factor.
AB  - OBJECTIVE: To assess the significance of onabotulinumtoxinA (onabotA)
      intravesical administration in blocking autonomic dysreflexia (AD) response
      induced by cystometrogram (CMG) after T4 spinal cord transection (SCT). MATERIALS
      AND METHODS: Female rats were stratified into three groups: a sham group; a SCT
      only group; and a SCT with onabotA treatment group. Each group was further
      subdivided into two subgroups: AD assessment, or nerve growth factor (NGF)
      assessment via enzyme-linked immunosorbent assay (ELISA). Three weeks after T4
      SCT, all groups were assessed. Arterial pressure and heart rate were measured
      during and after CMG. NGF was also extracted from the bladder and the dorsal root
      ganglia (DRG) of the T4 root and quantified by ELISA. In the onabotA-treated
      group, 48 h before assessment, onabotA (1 mL, 20 U/mL in saline) was given using
      a urethral tube and was left indwelling for 30 min. Univariate anova was used to
      analyse the data and statistical significance was set at P < 0.05. RESULTS: The
      maximum voiding pressure and the number of uninhibited contractions were
      significantly lower in the group treated with intravesical onabotA than in the
      SCT-only group. Intravesical onabotA significantly blocked the dysreflexia
      response (high arterial pressure with bradycardia) induced by CMG after SCT.
      Intravesical onabotA also significantly lowered NGF concentrations in the bladder
      and the T4 DRG segment. CONCLUSIONS: The results of the present study showed that
      intravesical onabotA controls neurogenic detrusor overactivity and AD after SCT.
      The findings shed light on the potential benefits of intravesical onabotA
      treatment in patients with spinal cord injury, and also provide a novel mechanism
      for the control of AD via a minimally invasive treatment modality.

PMID- 21733077
TI  - Delayed proximal ureteric stricture formation after complex partial nephrectomy.
AB  - OBJECTIVE: *  To report and review our incidence of delayed ureteric stricture
      (US) after complex nephron-sparing surgery (NSS). PATIENTS AND METHODS: *  Using
      our institutional kidney cancer database, we identified 720 patients who
      underwent NSS from 1 January 2000 until 31 December 2010 and identified eleven
      (1.5%) patients with a delayed US. *  Patient and tumour characteristics were
      reviewed. RESULTS: *  Median (range) tumour size and RENAL nephrometry score was
      4.1 (2-7.2) cm and 10p (4-11p), respectively. *  There were eight of 10 solitary
      tumours (80%) located in the lower or mid-pole of the kidney. *  There were eight
      of 11 patients with delayed US (72.7%) who experienced a postoperative urinary
      leak. *  There were two of 11 (18.2%) patients who experienced a postoperative
      retroperitoneal haemorrhage, with one of these patients requiring selective
      embolization. *  All US were in the upper third of the ureter and were diagnosed
      at a minimum of 10 weeks postoperatively (median 154 days, range 70-400 days).
      CONCLUSIONS: *  US formation is an uncommon and under-reported event after
      complex NSS. *  Risk factors appear to include tumour complexity, imperative
      indications, mid- or lower pole location, postoperative urinary leak and
      haemorrhage. *  Although uncommon, postoperative US can occur after NSS for
      complex renal masses, necessitating patient counselling and diligent
      postoperative surveillance.

PMID- 21733078
TI  - Air-filled postcranial bones in theropod dinosaurs: physiological implications
      and the 'reptile'-bird transition.
AB  - Pneumatic (air-filled) postcranial bones are unique to birds among extant
      tetrapods. Unambiguous skeletal correlates of postcranial pneumaticity first
      appeared in the Late Triassic (approximately 210 million years ago), when they
      evolved independently in several groups of bird-line archosaurs (ornithodirans).
      These include the theropod dinosaurs (of which birds are extant representatives),
      the pterosaurs, and sauropodomorph dinosaurs. Postulated functions of skeletal
      pneumatisation include weight reduction in large-bodied or flying taxa, and
      density reduction resulting in energetic savings during foraging and locomotion.
      However, the influence of these hypotheses on the early evolution of pneumaticity
      has not been studied in detail previously. We review recent work on the
      significance of pneumaticity for understanding the biology of extinct
      ornithodirans, and present detailed new data on the proportion of the skeleton
      that was pneumatised in 131 non-avian theropods and Archaeopteryx. This includes
      all taxa known from significant postcranial remains. Pneumaticity of the cervical
      and anterior dorsal vertebrae occurred early in theropod evolution. This 'common
      pattern' was conserved on the line leading to birds, and is likely present in
      Archaeopteryx. Increases in skeletal pneumaticity occurred independently in as
      many as 12 lineages, highlighting a remarkably high number of parallel
      acquisitions of a bird-like feature among non-avian theropods. Using a
      quantitative comparative framework, we show that evolutionary increases in
      skeletal pneumaticity are significantly concentrated in lineages with large body
      size, suggesting that mass reduction in response to gravitational constraints at
      large body sizes influenced the early evolution of pneumaticity. However, the
      body size threshold for extensive pneumatisation is lower in theropod lineages
      more closely related to birds (maniraptorans). Thus, relaxation of the
      relationship between body size and pneumatisation preceded the origin of birds
      and cannot be explained as an adaptation for flight. We hypothesise that skeletal
      density modulation in small, non-volant, maniraptorans resulted in energetic
      savings as part of a multi-system response to increased metabolic demands.
      Acquisition of extensive postcranial pneumaticity in small-bodied maniraptorans
      may indicate avian-like high-performance endothermy.

PMID- 21733079
TI  - Evolution of Hepatitis B and C serum markers: a still challenging issue.

PMID- 21733080
TI  - Is poor quality of life always present with minimal hepatic encephalopathy?

PMID- 21733081
TI  - Insulin-like growth factor-I and the liver.
AB  - Insulin-like growth factors (IGFs) play an essential role in growth and
      development, as well as in the overall cellular regulation and metabolism in the
      human body. In chronic liver disease, IGF levels are decreased, and the
      circulating levels correlate to the extent of hepatocellular dysfunction.
      Patients with cirrhosis are characterised by a variety of metabolic disturbances,
      including nutritional and metabolic complications such as insulin resistance,
      malnutrition, osteopenia and hypogonadism, all related to IGF-I deficiency. The
      complex process of hepatic fibrogenesis and the systemic consequences in
      cirrhosis are only partly understood. Disruption of the growth hormone (GH)-IGF-I
      axis seems to be closely associated with the development of liver disease, and
      treatment with recombinant human IGF (rhIGF)-I has been shown to halt, and even
      reverse, the fibrotic degeneration. IGF-I in itself has a strong antifibrotic
      effect that acts directly through the GH/IGF system and indirectly by the
      regulation of hepatoprotective and profibrogenic factors. It is most likely that
      IGF-I deficiency contributes to the diverse metabolic complications of cirrhosis.
      At present, liver transplantation remains the only efficient treatment of
      cirrhosis, and thus new methods of managing the disease are called for. RhIGF-I
      supplementation and IGF-I gene therapy may represent future perspectives of
      treatment.

PMID- 21733082
TI  - The role of the innate immune recognition system in the pathogenesis of primary
      biliary cirrhosis: a conceptual view.
AB  - The aetiology of primary biliary cirrhosis (PBC) remains unknown. Infectious and
      non-infectious noxious insults in combination with tissue-specific factors may
      precipitate PBC. Activation of innate immune response because of impending danger
      signals seems to be a key event in early PBC, as evidenced by granuloma
      formation, eosinophilic reaction and IgM elevation. Aberrant mitophagy in
      'stressed' biliary epithelia cells may initiate the immune response against
      mitochondrial antigens. Antimitochondrial autoantibodies recognize evolutionarily
      conserved molecules. The question arises, whether they are pathogenic or rather
      an expression of beneficial autoimmunity. The generally stable course of PBC
      suggests that stimulatory and inhibitory autoimmune reactions govern the
      inflammatory biliary process. Tissue repair and defense are the heart of innate
      immunity. But continuous exposure of exogenous stimuli may precipitate functional
      antireceptor autoantibodies that are no more protective but rather harmful.
      Mitophagy, apoptosis and bile duct proliferation define the inflammatory response
      within bile ducts. Autoantigens may be clustered in different blebs on the
      surface of apoptotic cells targeting a variety of membrane and non-membrane
      associated antigens. Thus, the autoantibody response in PBC may target, for
      instance, the pro- and anti-apoptotic proteins of the Bcl-2 family or receptors
      of the adrenergic or cholinergic system, hereby interfering with the programme of
      apoptosis and the proliferation of biliary epithelial cells. Consideration of
      there being functional autoantibodies into the pathogenesis of PBC may help to
      improve our understanding of the aetiopathogenesis of PBC.

PMID- 21733083
TI  - Recombinant hepatocyte growth factor treatment in a canine model of congenital
      liver hypoplasia.
AB  - BACKGROUND: Although the liver has a large regenerative capacity, in many
      hepatopathies, these repair mechanisms fail. The therapeutic potential of
      hepatocyte growth factor (HGF) has been proven in numerous toxin-induced liver
      failure models in rodents, but never in spontaneously occurring liver diseases in
      larger animal models. AIM: The aim of this study was to induce liver growth in a
      hypoplastic liver by the administration of exogenous recombinant HGF. The natural
      hypoplastic liver model used is the canine congenital portosystemic shunt (CPSS)
      characterized by strongly reduced liver growth and function. METHODS: Recombinant
      HGF (rHGF), 200 MUg/kg, was given twice daily during 3 weeks by an intravenous
      injection in six dogs with CPSS. Liver volumes were determined by computed
      tomography before and at 1, 2, 3 and 7 weeks after the initiation of treatment.
      Portosystemic shunting was evaluated with an ammonia tolerance test and liver
      portal perfusion was quantified with scintigraphy. Simultaneously, blood
      parameters for liver function were assayed and liver biopsies were taken for
      histology, immunohistochemistry and gene-expression measurements. RESULTS: During
      3 weeks of HGF treatment, hepatocyte proliferation increased and an increase in
      liver volume up to 44% was seen, persisting in two dogs up to 4 weeks after the
      termination of treatment. Ki-67 expression, gene expression of E2F1 and CDC6,
      phosphorylated-c-MET and phosphorylated-ERK1/2 protein levels confirmed increased
      hepatocyte proliferation and HGF signalling. The aberrant portal perfusion did
      not change during treatment. CONCLUSIONS: Transient in vivo liver growth is shown
      using CPPS as a naturally occurring large animal model, indicating the
      therapeutic potential of HGF in liver disease.

PMID- 21733084
TI  - Chronic alcohol-induced liver disease inhibits dendritic cell function.
AB  - BACKGROUND/AIMS: We have compared dendritic cell (DC) function derived from the
      alcoholic liver disease (ALD) sensitive Long-Evans (LE) and resistant Fischer rat
      strains to determine if the influence of ethanol on DCs was dependent on ALD.
      METHODS: The LE and Fischer rats were fed an ethanol-containing or isocaloric
      control liquid diet for 8 weeks and comparisons were made to LE rats injected
      with thioacetamide as a liver disease control. DCs were isolated from the spleen
      after expansion with human Fms-like tyrosine kinase receptor 3 ligand plasmid.
      Maturation markers CD86, CD80, CD40 and MHC-II were analysed by flow cytometry
      with or without lipopolysaccharide and poly I:C stimulation. Production of tumour
      necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)
      12p40 and IL-10 cytokines and the antigen presentation ability of DCs was
      determined. RESULTS: Only LE rats developed ALD characterized by liver injury,
      elevated alanine aminotransferase levels and steatosis; CD86 and CD40 expression
      was decreased in LE but not Fischer rats. Reduced TNF-alpha, IFN-gamma, IL-12,
      proinflammatory and enhanced IL-10 cytokine production was found in DCs isolated
      from ethanol-fed LE but not Fischer rats. Allostimulatory activity was reduced in
      LE compared with the Fischer strain. In contrast, DCs isolated from thioacetamide
      induced liver damage displayed a reduction only in IL-12p40; TNF-alpha, IL-10 and
      IFN-alpha production as well as antigen presenting ability remained intact
      compared with controls. CONCLUSIONS: ALD sensitive LE rats exhibited
      characteristics of a suppressed DC phenotype that was not observed following
      thioacetamide-induced liver disease, which suggests an important role for ALD in
      altering the host cellular and humoral immune responses.

PMID- 21733085
TI  - Brain biomolecules oxidation in portacaval-shunted rats.
AB  - BACKGROUND: Oxidative stress induced by a high ammonia concentration has been
      suggested to be implicated in the pathophysiology of hepatic encephalopathy (HE).
      Therefore, oxidative damage of brain biomolecules could contribute towards
      explaining the neurological and motor alterations observed in HE. METHODS:
      Portacaval-shunted (PCS) rats (n = 5) were used as an animal model of chronic HE.
      Plasma and brain ammonia were measured by the l-glutamate dehydrogenase method.
      Reactive oxygen species was measured by the dichlorodihydrofluorescein diacetate
      method. Lipid peroxidation was measured as thiobarbituric acid-reactive
      substances (TBARS) by a colorimetric method; malondialdehyde (MDA) and 4-hydroxy
      2-noneal (HNE) were measured by HPLC and an immunological method respectively.
      Protein oxidation (carbonylation) was measured as total carbonyl after labelling
      with 2,4-dinitrophenyl hydrazine (DNPH) using a spectrophotometric method.
      Individual protein oxidation was studied, after labelling with DNPH and its
      separation by one-dimensional (1D) electrophoresis, by an immunological method.
      RESULTS: Ammonia-induced oxidative stress in PCS rats was associated with
      increased MDA and HNE, together with increased protein oxidation, evidenced by
      total carbonyl quantification and by the analysis of individual protein bands
      separated by 1D electrophoresis. However, lipid peroxidation measured as TBARS
      did not show differences. CONCLUSION: Our data show an increased evidence of
      oxidative stress in PCS rat brain; moreover, PCS rat brain proteins are oxidized
      (carbonylated), some proteins being more sensitive to oxidation than others.
      These data also show that at least six specific brain proteins in PCS rats are
      highly sensitive to carbonylation. Identification of these proteins may be
      crucial for a better understanding of HE pathophysiology.

PMID- 21733086
TI  - An incidentally found complex cystic lesion in the liver.

PMID- 21733087
TI  - Minimal hepatic encephalopathy does not impair health-related quality of life in
      patients with cirrhosis: a prospective study.
AB  - BACKGROUND: Minimal hepatic encephalopathy (HE) is a serious complication of
      cirrhosis; however, the impact of minimal HE on health-related quality of life
      (HRQoL) remains controversial. The Psychometric Hepatic Encephalopathy Score
      (PHES) remains a 'gold standard' for the assessment of minimal HE, but its
      results clearly differ between studied populations. AIM: We studied the effect of
      minimal HE on patient HRQoL. METHODS: Eighty-seven consecutive cirrhotic patients
      were included. All patients underwent clinical and psychometric evaluation at the
      same day. Ten subjects with overt HE confirmed with West Haven criteria were
      excluded from the study, thus 77 patients were finally analysed. Patients with
      minimal HE were identified on the grounds of altered PHES. HRQoL was assessed by
      the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and the
      Chronic Liver Disease Questionnaire (CLDQ). Normative reference data for PHES
      were established from a cohort of 305 healthy Polish subjects. RESULTS: Twenty
      nine (37.7%) patients were diagnosed with minimal HE. When patients with and
      without minimal HE were compared, HRQoL was not significantly different in none
      of the SF-36 and CLDQ domains. CONCLUSION: Minimal HE does not affect HRQoL.

PMID- 21733088
TI  - Hepcidin response to acute iron intake and chronic iron loading in dysmetabolic
      iron overload syndrome.
AB  - BACKGROUND: The pathogenesis of dysmetabolic iron overload syndrome (DIOS) is
      still unclear. Hepcidin is the key regulator of iron homeostasis controlling iron
      absorption and macrophage release. AIM: To investigate hepcidin regulation by
      iron in DIOS. METHODS: We analysed urinary hepcidin at baseline and 24 h after a
      65 mg oral iron dose in 24 patients at diagnosis and after iron depletion (n =
      13) and compared data with those previously observed in 23 healthy controls.
      Serum iron indices, liver histology and metabolic data were available for all
      patients. RESULTS: At diagnosis, hepcidin values were significantly higher than
      in controls (P < 0.001). After iron depletion, hepcidin levels decreased to
      normal values in all patients. At baseline, a significant response of hepcidin to
      iron challenge was observed only in the subgroup with lower basal hepcidin
      concentration (P = 0.007). In iron-depleted patients, urinary hepcidin
      significantly increased after oral iron test (P = 0 .006). CONCLUSIONS: Ours
      findings suggest that in DIOS, the progression of iron accumulation is
      counteracted by the increase in hepcidin production and progressive reduction of
      iron absorption, explaining why these patients develop a mild-moderate iron
      overload that tends to a plateau.

PMID- 21733089
TI  - Role of hepatitis E infection in acute on chronic liver failure in Egyptian
      patients.
AB  - BACKGROUND: The vast majority of patients who are referred to a specialist
      hepatological centre suffer from acute deterioration of their chronic liver
      disease. Yet, this entity of acute on chronic liver failure remains poorly
      defined. AIM: The aim of the present study was to highlight the occurrence of
      hepatitis E viraemia by nested reverse transcriptase polymerase chain reaction
      (RT-PCR) in patients with acute on chronic liver failure. MATERIALS AND METHODS:
      The study included 100 patients with acute on chronic liver disorders admitted to
      Mansoura University Hospital, Egypt. Blood samples were obtained from patients
      and sera were separated. Sera were subjected to a study of viral hepatitis
      markers for hepatitis A by IgM, for hepatitis B by S antigen and core IgM and for
      hepatitis C virus by IgG and RT-PCR for HCV. Liver function tests were evaluated
      including alanine transaminase, aspartate transaminase and bilirubin total and
      direct by an autoanalyser. Study for hepatitis E virus (HEV) was performed using
      a molecular technique. Nested RT-PCR was performed for each serum sample.
      RESULTS: HEV RNA was detected in the sera of 13 patients (13%) of the patients
      with chronic liver disorders. The majority of the positive cases were among
      patients with cirrhosis (29.9%) followed by patients with HCC (15.4%). On
      multirisk analysis for the factors associated with the presence of HEV viraemia,
      younger age < 45 years and lower albumin level < 3.5 g/dl were significantly (P =
      0.04, P = 0.03) associated with HEV viraemia. DISCUSSION: From this study it
      appears that HEV viraemia is a common cause of acute on chronic liver disorders
      in Egypt. CONCLUSION: There is no effective vaccine is available against HEV,
      mass awareness and preventive measures are important to the related.

PMID- 21733090
TI  - Association of mannose-binding lectin-2 gene polymorphism with the development of
      hepatitis C-induced hepatocellular carcinoma.
AB  - BACKGROUND: Development of end-stage liver and graft disease is suspected to be
      partially determined by the individual genetic background. Mannose-binding lectin
      (MBL) is an important immunomodulatory factor, which is supposed to be involved
      in complement activation and oncogenesis. Genetic polymorphisms of MBL-2 alter
      MBL functionality. The aim of our study was to determine the prevalence of MBL-2
      polymorphism (rs7096206) in hepatitis C virus (HCV)-induced hepatocellular
      carcinoma (HCC) based on histological analysis of explanted livers in patients
      undergoing liver transplantation (LT). METHODS: One hundred and seventy-seven
      patients, who underwent LT for HCV-induced liver disease, were genotyped for MBL
      2 by TaqMan genotyping assay. Sixty-two patients with histologically confirmed
      HCC were compared with 115 patients without HCC. MBL-2 genotypes were corelated
      with the growth patern, tumour size and pretransplant alpha-fetoprotein (AFP)
      level of HCC patients. RESULTS: The prevalence of GG/GC genotypes was
      significantly higher among HCC patients compared with tumour-free explanted
      livers (P = 0.004; odds ratio 2.5; 1.3-4.8). GG/GC genotype group was
      significantly associated with the size of HCC (P = 0.022), higher pretransplant
      AFP level (P = 0.010) and bilobar tumour growth (P = 0.038). Furthermore, CC
      genotype was found to be significantly more frequent in AFP-negative HCCs (P =
      0.002). CONCLUSION: Mannose-binding lectin-2 polymorphism seems to be involved in
      the development of pretransplant HCV-induced HCC and should be further
      investigated as potential risk factor for HCV-associated carcinogenesis.

PMID- 21733091
TI  - Diagnostic value and utility of the simplified International Autoimmune Hepatitis
      Group criteria in acute-onset autoimmune hepatitis.
AB  - BACKGROUND: The diagnosis of autoimmune hepatitis (AIH) is already difficult, and
      that of acute-onset AIH with atypical features is even more challenging, even
      though the revised original diagnostic criteria created by an international AIH
      group were widely accepted and incorporated into clinical practice. AIMS:
      Recently, simplified diagnostic criteria were proposed. We compared the
      performance parameters of the simplified scoring system in patients with acute
      onset AIH and examined its usefulness and limitations. METHODS: Fifty-five
      patients with acute-onset AIH (29 non-severe, 14 severe and 12 fulminant) were
      assessed according to the simplified scoring system and compared with the revised
      original one. RESULTS: Of the 55 patients, 22 (40%) were diagnosed as 'definite'
      AIH, 28 (51%) as 'probable' and five (9%) as 'non-diagnostic' based on the
      revised original scoring system. By the simplified scoring system, six (11%) were
      diagnosed as 'definite' AIH, 16 (29%) as 'probable' and 33 (60%) as 'non
      diagnostic'. Anti-nuclear antibody titres did not differ among the three groups.
      The immunoglobulin G level was higher in fulminant than in non-severe patients (P
      = 0.01). Sixty-five per cent showed acute hepatitis (massive necrosis, submassive
      necrosis and severe acute hepatitis) and 35% showed chronic hepatitis.
      CONCLUSIONS: The revised original scoring system performed better in patients
      with acute-onset AIH than the simplified scoring system.

PMID- 21733092
TI  - Liver transplantation using donor organs with markedly elevated liver enzymes:
      how far can we go?
AB  - BACKGROUND: The disparity between the demand for solid organs and the current
      supply is a growing problem for patients with end-stage liver disease. To
      overcome organ shortage, extended criteria donor organs are also accepted for
      liver transplantation. AIMS: We here unprecedentedly report the clinical course
      of patients receiving livers with markedly elevated liver enzymes. METHODS:
      Between November 2007 and December 2010, 15 donor livers with markedly elevated
      liver enzymes [median aspartate aminotransferase (AST) 1400 (500-7538) U/l,
      median alanine aminotransferase (ALT) 1026 (308-9179) U/l] were offered to our
      transplant centre. Based on elaborate judgment, seven of these donor livers were
      rejected and eight donor livers were transplanted. RESULTS: All eight
      transplanted patients showed a liver enzyme peak on the day of surgery (AST 2076
      +/- 1808 U/l, ALT 1087 +/- 833 U/l) and a statistically significant decrease from
      day 0 to day 7 post-liver transplantation. INR decreased and platelet count
      increased statistically significantly within 1 week after liver transplantation.
      The patients were discharged from the hospital 28 +/- 11 days after liver
      transplantation in good clinical condition. CONCLUSIONS: These data demonstrate
      that using donor livers with markedly elevated liver enzymes may be an acceptable
      option to expand the donor pool. Universal objective parameters for acceptance
      should be defined in future studies.

PMID- 21733093
TI  - Influence of hepatitis C virus on neurocognitive function in patients free from
      other risk factors: validation from therapeutic outcomes.
AB  - BACKGROUND AND AIMS: Mild neurocognitive dysfunction and altered cerebral proton
      magnetic resonance spectroscopy ((1) H-MRS) have been demonstrated in patients
      with chronic hepatitis C (CHC). This longitudinal study aimed to quantify these
      abnormalities in a cohort of patients free from correlated risk factors and
      determine whether treatment-induced viral clearance abolished these
      abnormalities. METHODS: Treatment-naive, non-cirrhotic patients with CHC,
      rigorously screened and excluded for other causes of impaired neurocognition,
      underwent neurocognitive testing, (1) H-MRS and evaluation for quality of life
      (QOL), mood and fatigue, before and 6 months after the completion of antiviral
      therapy. A comparison group of healthy controls was similarly assessed at
      baseline and 1 year later. RESULTS: Post-treatment results in 40 patients with
      CHC [31 sustained virological responders, hepatitis C virus (HCV)-R and 9 non
      responders, HCV-NR] were compared with their pretreatment results, and with the
      baseline and follow-up assessments of 39 healthy controls. Before receiving
      treatment, patients had impaired learning efficiency, poorer QOL and higher
      fatigue scores compared with the controls. Viral clearance was associated with a
      significant albeit small improvement in the QOL score that did not reach control
      levels. Cerebral (1) H-MRS demonstrated a lower N-acetyl aspartate/creatine (CRE)
      ratio in the globus pallidus (GP) of patients with hepatitis C, which was
      unchanged with viral clearance. The GP choline/CRE ratio increased in HCV-R
      following treatment, without a correlation with cognitive measures. CONCLUSIONS:
      The hepatitis C virus has a measurable effect on CNS integrity in patients
      screened for other medical and/or psychiatric comorbidities. Viral clearance has
      not been demonstrated to abolish these abnormalities.

PMID- 21733094
TI  - Updated thresholds for alanine aminotransferase do not exclude significant
      histological disease in chronic hepatitis C.
AB  - BACKGROUND AND AIM: Histological changes in hepatitis C virus (HCV)-infected
      patients with persistently normal alanine aminotransferase (PNALT) have not been
      evaluated for updated upper limits of normal (ULN; <= 19/30 U/L for
      females/males). We assessed significant fibrosis (>= F2, METAVIR) in patients
      with PNALT and persistently elevated alanine aminotransferase (PEALT). PATIENTS
      AND METHODS: Nine hundred and twenty consecutive, unselected HCV patients were
      stratified into four groups: Group I: (n = 124) PNALT within the updated ULN [0.5
      * ULN (corresponding to <= 19 U/L) for females; 0.75 * ULN (corresponding to <=
      30 U/L) for males]; Group II (n = 173): PNALT <= 1 * ULN but greater than Group
      I; Group III (n = 313): PEALT 1-2 * ULN; and Group IV (n = 310): PEALT > 2 * ULN.
      PNALT was defined as >= 3 determinations within the normal range over >= 6
      months. RESULTS: Advanced >= F3 and >= F2 fibrosis increased incrementally across
      Groups I; II; III; and IV: 24.2 and 45.2%; 25.4 and 56.1%; 36.1 and 64.2%; and 50
      and 77.1% respectively (P<0.0001 for both). Multivariable logistic regression
      analysis identified age [odds ratio (OR), 1.05; 95% confidence intervals (CI):
      1.02-1.08; P<0.0001], alanine aminotransferase (ALT) groups (OR 1.38; 95% CI:
      1.03-1.83; P = 0.030), presence of moderate-severe steatosis (OR 2.70; 95% CI:
      1.19-6.15; P = 0.018) and >= A2 necroinflammation (OR 17.9; 95% CI: 8.88-36.20; P
      < 0.0001) as independent predictors of >= F2 fibrosis. Updated ULN for ALT were
      better at excluding >= F2 fibrosis compared with traditional ULN (90.6 vs. 74.2%,
      P = 0.0041) but less specific (20.8 vs. 44%, P = 0.0007) with similar
      positive/negative predictive values. CONCLUSIONS: HCV patients with 'updated'
      normal ALT have the lowest prevalence of significant fibrosis, although utilizing
      these levels without resorting to biopsy would miss significant fibrosis in
      almost one-half of such patients.

PMID- 21733095
TI  - The effect of caffeine and alcohol consumption on liver fibrosis - a study of
      1045 Asian hepatitis B patients using transient elastography.
AB  - BACKGROUND: Role of caffeine consumption in chronic hepatitis B virus (HBV)
      infected patients and the interaction with alcohol consumption is unclear. AIM:
      This study aimed to investigate the relationship between caffeine and alcohol
      consumption and liver stiffness in chronic HBV-infected patients. METHODS:
      Chronic HBV-infected patients who underwent transient elastography examination in
      2006-2008 were studied. Advanced fibrosis was defined as liver stiffness > 9 kPa
      for patients with normal alanine aminotransferase (ALT) or > 12 kPa for those
      with elevated ALT according to previous validation study. Caffeine and alcohol
      consumption was recorded using a standardized questionnaire. Excessive alcohol
      intake was defined as 30 g/day in men and 20 g/day in women. RESULTS: The liver
      stiffness of 1045 patients who completed the questionnaire was 8.3 +/- 6.2 kPa.
      Two hundred and sixteen (20.7%) patients had advanced fibrosis. Ninety-five
      (19.0%) patients who drank >= 1 cup of coffee had advanced fibrosis, compared
      with 121 (22.2%) patients who drank < 1 cup (P = 0.21). The amount of caffeine
      intake had positive correlation with the amount of alcohol intake (r(s) = 0.167,
      P < 0.001). Although 231 (22.1%) patients reported alcohol consumption, only 11
      (1%) had excessive alcohol intake. The prevalence of advanced fibrosis among
      patients with mild to moderate alcohol intake (26, 18.8%) was comparable to that
      among non-drinkers (190, 21.0%) (P = 0.57). CONCLUSION: Caffeine intake does not
      affect liver stiffness in chronic HBV-infected patients. Patients who drink
      coffee regularly tend to drink alcohol. Most chronic HBV-infected patients do not
      have excessive alcohol consumption. The prevalence of advanced fibrosis among
      mild to moderate alcohol drinkers was low in this population.

PMID- 21733096
TI  - Liver transplantation with donors over the expected lifespan in the model for end
      staged liver disease era: is Mother Nature punishing us?
AB  - BACKGROUND: The lack of sufficient donors to satisfy the waiting list
      requirements has prompted many to expand the acceptance criteria. The purpose of
      this study was to evaluate our liver transplantation (LT) experience with donors
      beyond the average lifespan. PATIENTS AND METHODS: From January 2008 to December
      2009, we received 75 liver offers involving donors >= 75 years of age. Donor and
      recipient data were analysed by both uni- and multivariate Cox proportional
      hazard model analyses. RESULTS: We performed 32 adult liver transplants (43%).
      Half of the patients received organs through rescue allocations. Seven recipients
      (22%) developed initial poor function. Two had primary graft non-function (PNF).
      Four recipients were re-transplanted (two PNF and two ischaemic-type bile
      lesions). One- and 3-year cumulative survival was 62 and 51% respectively. PNF,
      lab model for end-staged liver disease (MELD), post-LT haemodialysis, post-LT re
      operations and post-LT sepsis were significant predictors by univariate analysis.
      Only PNF reached multivariate significance (P = 0.0307). Rescue offer allocation
      reached significance as a predictor of PNF by general linear model forward
      analysis. One- and 3-year 'MELD based allocation' (n = 16) vs 'rescue allocation'
      (n = 16) survival rates were 44 and 29% vs 82 and 76% respectively (P = 0.0197).
      CONCLUSIONS: Although grafts from donors >= 75 years allow for an expansion of
      the donor pool, long-term recipient survival is inferior to that encountered with
      younger donors. Acceptable results could be obtained by identifying 'preferred'
      recipients for rescue allocations.

PMID- 21733098
TI  - Tumour necrosis factor-alpha promoter region polymorphisms and spontaneous HBsAg
      clearance.

PMID- 21733099
TI  - Towards a rational use of low-molecular-weight heparin in patients with
      cirrhosis.

PMID- 21733100
TI  - Dosing and monitoring of low-molecular-weight heparin in cirrhotic patients.

PMID- 21733101
TI  - Evidence-based practice: what evidence counts?

PMID- 21733102
TI  - Defining male support during and after pregnancy from the perspective of HIV
      positive and HIV-negative women in Durban, South Africa.
AB  - INTRODUCTION: Greater male support during pregnancy and in the postpartum period
      may improve health outcomes for mothers and children. To develop effective
      strategies to engage men, we need to first understand the ways that men are
      currently engaged and the barriers to their greater involvement. METHODS: We
      conducted in-depth interviews in isiZulu with 30 HIV-positive women and 16 HIV
      negative women who received prenatal care from a public clinic in Durban, South
      Africa. Interviews were audiotaped, transcribed, translated, and coded for
      analysis. RESULTS: Although less than a quarter of women reported that their
      partners accompanied them to the clinic, they described receiving other material
      and psychosocial support from partners. More HIV-positive women reported that
      their partners were not involved or not supportive, and in some cases direct
      threats and experiences with violence caused them to fear partner involvement.
      DISCUSSION: We need to broaden the lens through which we consider male support
      during pregnancy and in the postpartum period and acknowledge that male
      involvement may not always be in the best interest of women. Engaging supportive
      partners outside of the clinic setting and incorporating other important social
      network members are important next steps in the effort to increase support for
      women.

PMID- 21733103
TI  - Postpartum care: evaluation and experience among care providers and care
      receivers.
AB  - INTRODUCTION: There have been substantial alterations in the structure of
      postpartum care over the last several decades. Our aim was to investigate the
      perceived quality of, and satisfaction with, postpartum care among caregivers and
      care receivers in the maternity ward of a community hospital in Norway with about
      2600 births per year. METHODS: We conducted a cohort study of women giving birth
      and the caregiving staff in the maternity ward during a 7-month period. A
      questionnaire, with a Cronbach alpha coefficient above 0.8, was filled in
      anonymously, both by the staff in the ward and by the women. The questionnaire
      explored the respondents' evaluations of the information offered by the staff;
      the teaching of skills in child care and establishment of breastfeeding;
      assistance with practical tasks like making beds, serving meals, and keeping
      order in the room; visiting rules; level of noise in the ward; whether the
      pediatric service was adequate; length of the stay; and to what extent caregivers
      were able to respond to the individual needs of the mothers. Finally, the
      questionnaire explored the degree of kindliness communicated by the staff. Five
      extra questions in the women's questionnaire explored their personal experiences
      in the ward. RESULTS: The care receivers' evaluations of the maternity ward did
      not differ significantly from that of the caregivers in questions related to
      overall care and service. However, the mothers rated the importance of assistance
      with child care during the night significantly higher than did the staff.
      Responses to questions addressing noise in the ward demonstrated a higher
      tolerance among the mothers compared with the staff. In addition, mothers tended
      (but not a statistically significant result) to rate the quality of the teaching
      of child-care skills lower, compared with the staff's ratings. DISCUSSION: By
      exploring both the caregivers' and care receivers' evaluations and expectations
      of the actual services in the maternity ward, areas for enhancement of the
      quality of the ward and its services can be detected and carried out. The present
      study revealed 2 areas needing further focus: assistance with child care during
      the night and teaching of child-care skills during the stay. We believe that
      investigations that collect data from both caregivers and care receivers, by
      using adapted and validated questionnaires to gather information on quality and
      satisfaction with the maternity ward, are mandatory for improvement and
      continuous adaptation of health services.

PMID- 21733104
TI  - Lost in translation: reproductive health care experiences of Somali Bantu women
      in Hartford, Connecticut.
AB  - INTRODUCTION: Reproductive health problems are the leading cause of women's
      morbidity and mortality worldwide. In the United States, officially sponsored
      refugee women continue to face challenges in accessing reproductive health
      programs despite having access to health insurance. METHODS: The objective of
      this study was to explore the reproductive health experiences of 1 such
      population--Somali Bantu women in Connecticut--to identify potential barriers to
      care experienced by marginalized populations. The study was qualitative,
      consisting of key informant interviews, a focus group session, and a
      semistructured survey. RESULTS: Although all the women in the study reported
      having access to reproductive health care services, they also reported having
      unmet health needs resulting from barriers to care that included ethnic
      distinction/language barriers, passive acceptance of incorrect care, cultural
      discordance in family planning services, patient-provider sex discordance, and
      desire but limited scope for ownership in health care outcomes. The root cause of
      the various types of patient-provider discordance was the lack of recognition
      that the Somali Bantu are distinct in culture, language, and solidarity from
      ethnic Somalis, resulting in Language Line translation services being conducted
      in a Somali language that the Somali Bantu women did not understand. DISCUSSION:
      The results of the study primarily highlight the larger issue of information
      asymmetry within the health care system that, if left unaddressed, will persist
      as new vulnerable populations of refugees arrive in the United States.

PMID- 21733105
TI  - Postpartum depression and correlated factors in women who received in vitro
      fertilization treatment.
AB  - INTRODUCTION: Postpartum depression is a significant mental health problem that
      occurs more frequently in the first 4 weeks postpartum and also may occur later
      during the first postpartum year. Women who receive in vitro fertilization (IVF)
      treatment have a particular perinatal experience that may create postpartum
      mental health concerns. The purpose of this cross-sectional study was to evaluate
      factors associated with postpartum depression in women who received IVF
      treatment. METHODS: Sixty of 71 eligible postpartum women who were treated at an
      infertility treatment center and who conceived by IVF were included in this
      study, which used a self-administered, structured questionnaire. RESULTS: The
      prevalence of postpartum depression was 25%, including mild (16.7%), moderate
      (6.7%), and severe (1.7%). Pearson correlation analysis showed that the frequency
      of receiving IVF treatment and perceived stress were positively correlated with
      postpartum depression, whereas family function and social support were negatively
      correlated with postpartum depression. Multiple regression analysis showed that
      the frequency of receiving IVF treatment, birth method, and social support were
      significant predictive factors for postpartum depression when covariates were
      controlled (R(2) 56.6%). DISCUSSION: A higher frequency of IVF treatment,
      cesarean birth, and inadequate social support increase the possibility of
      postpartum depression, and clinicians should provide appropriate anticipatory
      education or counseling.

PMID- 21733106
TI  - Australian midwives' knowledge of antenatal and postpartum depression: a national
      survey.
AB  - INTRODUCTION: Emotional care provided by midwives may improve health and well
      being; reduce stress, trauma, and depressive symptoms; and enhance maternal
      outcomes in childbearing women. The provision of intrapartum and postpartum
      emotional care can be challenging and requires a good knowledge base for the
      provider to screen and assist distressed women. This study assessed Australian
      midwives' levels of knowledge and learning needs regarding antenatal depression
      and postpartum depression. METHODS: Eight hundred and fifteen members of the
      Australian College of Midwives completed a postal survey, which consisted of 20
      items drawn from the literature and the National Baseline Survey-Health
      Professional Knowledge Questionnaire. RESULTS: On average, respondents correctly
      answered 62.9% of items related to antenatal depression and 70.7% of questions
      about postpartum depression. Many midwives were unable to identify the risk
      factors (70.6%) or prevalence of antenatal depression (49.6%). Nearly all (98.3%)
      respondents underestimated the percentage of antenatally depressed women that
      attempts suicide. Significant percentages of midwives did not correctly identify
      the incidence (44.4%), onset period (71%), and treatment options (32%) associated
      with postpartum depression. About half did not understand the use of
      antidepressant medications (48.6%) and incorrectly reported that the Edinburgh
      Postnatal Depression Scale was a suitable instrument to assess symptoms of
      psychotic depression (43.8%). DISCUSSION: There are key knowledge deficits
      relating to onset of, assessment of, and treatment for depressive symptoms during
      the antenatal and postpartum periods. There is a need for continuing professional
      education to improve midwives' knowledge and competency in the assessment and
      care of women suffering depression.

PMID- 21733107
TI  - Racial discrimination and the black-white gap in adverse birth outcomes: a
      review.
AB  - INTRODUCTION: The purpose of this integrative review was to evaluate what is
      known about the relationship between racial discrimination and adverse birth
      outcomes. METHODS: A search of the Cumulative Index of Nursing and Allied Health
      Literature, MEDLINE, and PsycINFO was conducted. The keywords used were: preterm
      birth, premature birth, preterm delivery, preterm labor, low birth weight, very
      low birth weight, racism, racial discrimination, and prejudice. Ten research
      studies were reviewed. All of the studies included African American women in
      their samples, were conducted in the United States, and were written in English.
      We did not limit the year of publication for the studies. Data were extracted
      based on the birth outcomes of preterm birth, low birth weight, or very low birth
      weight. RESULTS: A consistent positive relationship existed between perceptions
      of racial discrimination and preterm birth, low birth weight, and very low birth
      weight. No relationship was found between racial discrimination and gestational
      age at birth. DISCUSSION: Future research should explore the effects of racial
      discrimination as a chronic stressor contributing to the persistent gap in birth
      outcomes between racial groups.

PMID- 21733108
TI  - An educational intervention to change planned behavior concerning midwife
      assisted out-of-hospital childbirth.
AB  - INTRODUCTION: 'The Business of Being Born' is a documentary film that reviews the
      history, economics, and culture of birth in the United States, with an emphasis
      on viewing low-risk birth as a natural and reasonably safe experience that does
      not require medical intervention. METHODS: A nonequivalent control group design
      with 468 American university students was used to examine the potential of 'The
      Business of Being Born' for changing attitudes toward, and planned behavior
      concerning, midwife-assisted out-of-hospital childbirth. RESULTS: Viewing the
      film had a large positive effect on planned behavior concerning midwife-assisted
      out-of-hospital childbirth. Rationales for planned behaviors indicated that trust
      and safety concerns accounted for the appeal of physician-assisted hospital
      childbirth over midwife-assisted out-of-hospital childbirth, but that viewing the
      film substantially tempered these concerns vis-a-vis midwife-assisted out-of
      hospital childbirth among a large portion of participants. DISCUSSION: The
      results indicate that 'The Business of Being Born' can increase awareness of and
      support for the midwifery profession, and that these changes may result in
      increased demand for midwifery services. However, proactive efforts must be taken
      to ensure that the film reaches its target audience.

PMID- 21733109
TI  - Anesthesia and analgesia-related preferences and outcomes of women who have birth
      plans.
AB  - INTRODUCTION: This study described anesthesia and analgesia-related preferences
      and outcomes of women who used a birth plan for labor and birth. METHODS: A
      prospective cohort study was conducted (N = 63). Data were abstracted from
      medical records, birth plans, and a follow-up survey. Descriptive statistics were
      used for analysis. RESULTS: Women who elected birth plans were primarily white,
      college-educated, primigravida, and under the care of a certified nurse-midwife.
      One-third of births were induced, 10% required instrumentation, and 29% were
      cesarean births. Nearly every birth was associated with at least 1 labor and
      birth complication, although most complications were minor. Analgesic preferences
      were reported to be the most important birth plan request. Greater than 50% of
      women requested to avoid epidural analgesia; however, 65% of women received
      epidural analgesia. On follow-up, greater than 90% of women who received epidural
      analgesia reported being pleased. The majority of women agreed that the birth
      plan enhanced their birth experiences, added control, clarified their thoughts,
      and improved communication with their health care providers. DISCUSSION:
      Anesthesia and analgesia-related preferences were an important component of the
      birth plans. The majority of women favorably viewed the use of a birth plan,
      whether or not preferences were fulfilled or complications occurred.

PMID- 21733110
TI  - International clinical experience for midwifery students.
AB  - INTRODUCTION: The purpose of this survey was to obtain information that would
      elucidate what types and amounts of international clinical experiences are
      available to midwifery students in accredited midwifery programs. Furthermore,
      the survey assessed the need for and interest in an online pre-trip preparation
      course and the possibility of future collaborative efforts between midwifery
      programs. METHODS: A formal electronic descriptive survey was sent to eligible
      directors of midwifery education (DOME) from 38 accredited institutions in the
      United States. RESULTS: Twenty-nine of 38 (76%) responded to the survey, and 9 of
      29 programs (31%) offer international clinical experiences. Sixteen (80%) of the
      20 programs not currently offering international experiences indicated interest
      in offering these experiences. Of the 9 programs that have international
      experiences, only 1 reported offering a formal pre-trip course. DISCUSSION: The
      results of this survey suggest that there is interest in collaborative efforts
      for developing a formal pre-trip preparation course and sharing international
      experiences that would promote sustainable programs of international experiences
      for student midwives.

PMID- 21733111
TI  - Stressful childbirth situations: a qualitative study of midwives.
AB  - INTRODUCTION: This study aimed to explore clinical life-threatening childbirth
      situations, which midwives perceive as extremely stressful, and to identify how
      midwives cope with those experiences. METHODS: Participants were 18 midwives
      employed in 6 labor and delivery units in Israeli hospitals. Individual
      semistructured, in-depth interviews were conducted wherein participants were
      asked to describe an extremely stressful situation that they had experienced,
      their significant feelings associated with the event, their coping strategies,
      and their support systems. RESULTS: Thematic content analysis revealed 2 themes,
      with each consisting of 4 categories. The first theme focused on reactions to
      stressful childbirth situations and their impact on midwives. Categories were:
      functioning professionally in an unexpected reality, emotional reactions,
      physical reactions, and long-term effects. The second theme related to coping
      with stressful situations, focusing on coping difficulties, and suggestions for
      change. Categories were: midwives' coping difficulties, their colleagues'
      reactions, their feelings about supervisory staff support, and their suggestions
      for meeting expressed needs. DISCUSSION: Stressful childbirth situations can have
      a long-term impact on midwives' professional and personal identities. Midwives
      need to feel supported and valued in order to deal with emotional stress.
      Incorporating clinical supervision by experienced midwives can serve as a
      supportive framework for other midwives.

PMID- 21733112
TI  - Integration of routine rapid HIV screening in an urban family planning clinic.
AB  - INTRODUCTION: Family planning centers can play an important role in HIV
      screening, education, and risk-reduction counseling for women who are sexually
      active. This article describes how 1 urban Title X-funded family planning clinic
      transitioned from using a designated HIV counselor for targeted testing to a
      model that uses clinic staff to provide integrated, routine, nontargeted, rapid
      HIV testing as standard of care. METHODS: Representative clinic staff members
      developed an integrated testing model that would work within the existing clinic
      flow. Education sessions were provided to all staff, signs promoting routine HIV
      testing were posted, and patient and clinician information materials were
      developed. A review of HIV testing documentation in medical charts was performed
      after the new model of routine, nontargeted, rapid HIV testing was integrated, to
      determine any changes in patient testing rates. A survey was given to all staff
      members 6 months after the transition to full integration of HIV testing to
      evaluate the systems change process. RESULTS: Two years after the transition, the
      rate of patients with an HIV test in the medical chart within the last 12 months
      increased 25.5%. The testing acceptance rate increased 17%. Sixteen HIV
      seropositive individuals were identified and linked into medical care. All
      surveyed clinic staff agreed that offering routine HIV screening to all patients
      is very important, and 78% rated the integration efforts as successful.
      DISCUSSION: Integrating routine HIV screening into a family planning clinic can
      be critical to identifying new HIV infections in women. This initiative
      demonstrated that routine, nontargeted, rapid HIV screening can be offered
      successfully as a standard of care in a high-volume, urban, reproductive health
      care setting. This description and evaluation of the process of changing the
      model of HIV testing in a clinic setting is useful for clinicians who are
      interested in expanding routine HIV testing in their clinics.

PMID- 21733115
TI  - Interpretation of auscultation findings: intermittent auscultation categories.

PMID- 21733116
TI  - Share with women. Newborn screening and hearing test.

PMID- 21733117
TI  - Share with women. Vitamin D.

PMID- 21733118
TI  - [Share with women. Weight gain during pregnancy].

PMID- 21733119
TI  - Thromboembolic disease in systemic vasculitis is associated with enhanced
      microparticle-mediated thrombin generation.

PMID- 21733120
TI  - Transgenic crops: an option for future agriculture.

PMID- 21733121
TI  - Benzo[a]pyrene exposure increases toxic biomarkers and morphological disorders in
      mouse cervix.
AB  - Benzo[a]pyrene (BaP) is a representative compound of polycyclic aromatic
      hydrocarbons exerting cytotoxicity and genotoxicity in the human liver, lung,
      stomach and skin. However, the toxic effect of BaP on cervical tissue remains
      unclear. This study was carried out to investigate the toxic effects of BaP on
      the cervix of ICR mice. Female mice were treated with BaP by intraperitoneal
      injection and oral gavage at a dose of 2.5, 5 and 10 mg/kg body-weight, twice a
      week for 14 weeks. BaP treatment caused a significant increase in the levels of
      MDA and IL-6 with significantly increased activity of CYP1A1, creatine kinase and
      aspartate aminotransferase (AST) and decreased activity of glutathione-S
      transferase in the cervix and liver. The relative cervix weight was markedly
      reduced in the intraperitoneal BaP injection groups, whereas only a slight
      reduction was observed in the oral gavage groups. The increase in weight
      decreased with increasing BaP dose. Moreover, BaP treatment induced significant
      pathomorphological changes in the cervical tissue and increased the mortality of
      the mice. Taken together, these results suggest that BaP causes a certain toxic
      effect on cervical tissue.

PMID- 21733122
TI  - Protein and DNA oxidation in different anatomic regions of rat brain in a mimetic
      ageing model.
AB  - It has been reported that d-galactose administration causes an increase in
      oxidative and osmotic stresses in several tissues of rodents. In this study, we
      established a brain ageing model by using d-galactose and investigated the
      concentrations of oxidative stress markers on the hippocampus, parietal and
      frontal lobes of male Sprague-Dawley rats. A mimetic ageing model was established
      by injecting d-galactose (60 mg/kg/day/i.p.) in the experimental group for 42
      days. At the end of this period, we tested spatial memory using the Morris water
      maze test. To investigate the magnitude of oxidative damage in proteins, lipids
      and DNA, we studied the concentrations of various oxidative stress parameters in
      the hippocampus, parietal and frontal lobes of the brain. Glial and neuronal cell
      oxidative damage was observed in each of the three anatomic regions. It was found
      that protein carbonyl groups and advanced oxidation product concentrations in the
      d-galactose applied group were significantly high in each of the three brain
      lobes compared with the control group. Thiol concentration was found to be
      decreased in the parietal lobe. A concurrent increase in lipid hydroperoxides was
      also observed in this lobe. On the other hand, 8-hydroxy-2'-deoxyguanosine
      concentration was significantly increased in the hippocampal lobe of rats in the
      experimental group when compared with the controls. The results obtained from the
      mimetic ageing model rats showed that various anatomical regions of brain have
      different susceptibility to oxidative damage of proteins, lipids and DNA.

PMID- 21733123
TI  - The influence of dosing time, variable compliance and circadian low-density
      lipoprotein production on the effect of simvastatin: simulations from a
      pharmacokinetic-pharmacodynamic model.
AB  - The aim of this study was to explore the influence of simvastatin dosing time,
      variable compliance and circadian cholesterol production on the reduction of low
      density lipoprotein (LDL). A published pharmacokinetic-pharmacodynamic (PKPD)
      model for simvastatin was identified and evaluated. A model for circadian LDL
      production was incorporated into the PKPD model. Reduction in LDL from baseline
      was simulated stochastically from the full model at dose levels of 10, 20, 40 and
      80 mg daily for 30 days. Simulated dosing times for each data set were morning
      (8.00 a.m.), evening (22.00 p.m.), evening with reduced compliance and evening
      for a hypothetical bioequivalent generic. Differences in LDL reduction from
      baseline between evening (33-43%) and morning dosing (31-43%) were negligible
      across a range of doses. Any differences were negated when variable compliance
      was considered. In addition, differences in simvastatin effect between morning
      and evening dosing were found to be within the range of LDL concentrations that
      would be permissible for a bioequivalent generic (at the lower limit) and hence
      are not likely to be important clinically. The results of this study suggest that
      taking simvastatin in the evening is not superior to morning dosing.

PMID- 21733124
TI  - Small artery remodelling in hypertension.
AB  - Increased blood pressure (essential hypertension) is associated with increased
      cardiovascular risk, and the condition is treated primarily with a view to
      reducing this parameter. However, in the early stages, the main pathological
      changes are increased peripheral resistance and altered cardiovascular structure.
      The aim of this MiniReview was to trace the endeavours over the past several
      decades to translate these findings into answering the question whether
      normalization of resistance vessel structure should be a target for therapy. This
      MiniReview describes first the altered structure of the resistance vasculature in
      essential hypertension, where the vessels show increased media/lumen ratio
      because of inward eutrophic remodelling. Secondly, evidence is presented that
      altered small artery structure appears to have prognostic consequences. Then, the
      cellular mechanisms that may be involved are discussed, where there is evidence
      that vasoconstriction in itself can cause inward remodelling and that this can be
      prevented by vasodilators. This leads to a discussion of the degree to which it
      may be possible to rectify the abnormal structure, where it appears that this may
      be achieved using a therapy that causes vasodilatation in the patient concerned.
      Finally, the consequences of these findings are considered as regards clues for
      strategies that may be able to improve the outcome of antihypertensive therapy.
      The MiniReview concludes that there is reasonably strong evidence that
      improvement in abnormal resistance vessel structure requires a treatment that
      reduces peripheral resistance in the individual patient.

PMID- 21733125
TI  - Improving the NQO1-inducing activities of phenolic acids from radix Salvia
      miltiorrhiza: a methylation strategy.
AB  - NAD(P)H: quinone oxidoreductase1 (NQO1) is an important detoxification enzyme
      that can protect mammalian cells against toxic quinones and reduce the risk of
      tumorigenesis. In this study, it was found that salvianolic acid B (SaB),
      lithospermic acid (LA), and rosmarinic acid (RA), three main hydrophilic
      constituents in Danshen, conjugated with glutathione (GSH) easily in vitro but
      exhibited no NQO1-inducing activities in Hepa 1c1c7 cells, which might attribute
      to their poor absorptions. After a simple methylation strategy that aimed at
      improving the liposolubility, both the NQO1-inducing activities and the
      absorptions in cells of the phenolic acids improved obviously, without losing the
      GSH-conjugating abilities. The concentration to double the specific activity of
      NQ01 values of methylated products of lithospermic acid and rosmarinic acid were
      17.86 +/- 2.34 MUg/mL and 11.97 +/- 0.60 MUg/mL, respectively. The findings
      indicated that methylation is an effective strategy to improve the NQO1-inducing
      activities of phenolic acids in Danshen.

PMID- 21733126
TI  - Single-cell genomics: unravelling the genomes of unculturable microorganisms.

PMID- 21733129
TI  - Insulin independence by supplemental islet transplantation 5 years after initial
      islet transplantation.

PMID- 21733127
TI  - Biotechnological uses of enzymes from psychrophiles.
AB  - The bulk of the Earth's biosphere is cold (e.g. 90% of the ocean's waters are <=
      5 degrees C), sustaining a broad diversity of microbial life. The permanently
      cold environments vary from the deep ocean to alpine reaches and to polar
      regions. Commensurate with the extent and diversity of the ecosystems that
      harbour psychrophilic life, the functional capacity of the microorganisms that
      inhabitat the cold biosphere are equally diverse. As a result, indigenous
      psychrophilic microorganisms provide an enormous natural resource of enzymes that
      function effectively in the cold, and these cold-adapted enzymes have been
      targeted for their biotechnological potential. In this review we describe the
      main properties of enzymes from psychrophiles and describe some of their known
      biotechnological applications and ways to potentially improve their value for
      biotechnology. The review also covers the use of metagenomics for enzyme
      screening, the development of psychrophilic gene expression systems and the use
      of enzymes for cleaning.

PMID- 21733130
TI  - Estimating the location and shape of hybrid zones.
AB  - We propose a new model to make use of georeferenced genetic data for inferring
      the location and shape of a hybrid zone. The model output includes the posterior
      distribution of a parameter that quantifies the width of the hybrid zone. The
      model proposed is implemented in the GUI and command-line versions of the
      Geneland program versions >= 3.3.0. Information about the program can be found on
      http://www2.imm.dtu.dk/gigu/Geneland/.

PMID- 21733131
TI  - UBE3A regulates MC1R expression: a link to hypopigmentation in Angelman syndrome.
AB  - Angelman syndrome (AS) is a neurogenetic disorder caused by the lack of
      functional ubiquitin-protein ligase E3A (UBE3A) that acts as an E3 ligase in the
      ubiquitin-proteosomal degradation pathway and/or as a transcriptional
      coactivator. Besides neurological deficit, hypopigmentation is another phenotype
      associated with AS patients currently attributed to the hemizygosity of the type
      II oculocutaneous albinism (OCA2) gene. Here we show that the melanocortin-1
      receptor (MC1R) is down-regulated in the skin of the Ube3a((-/-))  mice.
      Luciferase-reporter assay shows that UBE3A is able to induce MC1R promoter
      activity. Using chromatin immunoprecipitation assay, Ube3a was observed to be
      physically associated with the Mc1r promoter. Deletion of the E box/SP1 element
      in the MC1R minimal promoter abolishes the ability of UBE3A to elevate MC1R
      promoter-luciferase reporter activity. Ube3a((-/-))  mice also show relative skin
      hypopigmentation. These results demonstrate that UBE3A plays a role in MC1R
      transcriptional regulation which can contribute to the development of
      hypopigmentation in AS patients.

PMID- 21733132
TI  - Understanding foot-and-mouth disease virus early pathogenesis and immune
      responses.

PMID- 21733133
TI  - An investigation into alternative reservoirs of canine leishmaniasis on the
      endemic island of Mallorca (Spain).
AB  - The role of wild and free-roaming domestic carnivores as a reservoir of
      Leishmania infantum was investigated on the Mediterranean island of Mallorca
      (Balearic Islands, Spain), an endemic area for this disease. Serum, blood and/or
      spleen samples from 169 animals [48 dogs from a kennel, 86 wild-caught feral
      cats, 23 pine martens (Martes martes), 10 common genets (Genetta genetta) and two
      weasels (Mustela nivalis)] were analysed. Seroprevalence determined by Western
      blotting was 38% in dogs and 16% in feral cats, while the prevalence of infection
      determined by PCR was 44% in dogs, 26% in cats, 39% in pine martens and 10% in
      genets. This is the first report of infection by L. infantum in the pine marten
      or any other member of the Mustelidae family. Restriction fragment length
      polymorphism (RFLP) analysis found 33 different patterns in 23 dogs, 14 cats and
      three martens. Two patterns were shared by dogs and cats, two by different cats,
      and one by different dogs. Patterns were different to those previously reported
      in carnivores from peninsular Spain. No external lesions compatible with
      leishmaniasis were observed in any species other than the dogs. Although the dog
      is probably the primary reservoir of leishmaniasis in endemic areas, the
      prevalence and the absence of apparent signs of this disease within the island's
      abundant feral cat and pine marten populations could make these species potential
      primary or secondary hosts of L. infantum in Mallorca.

PMID- 21733134
TI  - Common, emerging, vector-borne and infrequent abortogenic virus infections of
      cattle.
AB  - This review deals with the aetiology and the diagnosis of bovine viral abortion.
      While the abortion rates on beef and dairy cattle farms usually do not exceed
      10%, significant economic losses because of abortion storms may be encountered.
      Determining the cause of abortions is usually a challenge, and it generally
      remains obscure in more than 50% of the necropsy submitted foetuses. Bovine viral
      diarrhoea virus and bovine herpesvirus-1 are the most common viruses causally
      associated with bovine abortions in farmed cattle globally. Rift Valley fever
      virus and bluetongue virus are important insect-transmitted abortogenic viruses.
      The geographic distribution of these two viruses is primarily dependent on the
      distribution of the insect vector, but direct transmission is possible. Recent
      global warming and subsequent insect vector expansion, coupled with the increase
      in international trade of animals and animal products, have been important
      factors in recent geographic advances of those two viruses. Bovine herpesviruses
      4 and 5 in cattle, as well as other less frequent vector-borne viruses including
      epizootic haemorrhagic disease virus, Aino virus, Wesselsbron virus and lumpy
      skin disease virus, are discussed.

PMID- 21733135
TI  - Review of biological factors relevant to import risk assessments for epizootic
      ulcerative syndrome (Aphanomyces invadans).
AB  - Epizootic ulcerative syndrome (EUS) is a disease affecting both wild and farmed
      fish in freshwater and estuarine environments. After it was first described in
      Japan in 1971, the disease has spread widely across Asia and to some regions of
      Australia, North America and Africa. In Asia and Africa, the spread of the
      disease has substantially affected livelihoods of fish farmers and fishermen. No
      reports are yet published showing the presence of the disease in Europe or South
      America. Given its epizootic nature and its broad susceptible fish species range,
      it would appear that the disease has the potential for further spread. This study
      provides a review of the scientific literature on several biological factors of
      the pathogen, Aphanomyces invadans, associated with the disease EUS and aspects
      of the disease that are relevant to undertaking import risk assessments (IRA)
      covering (i) Life cycle and routes of transmission; (ii) Minimum infectious dose;
      (iii) Tissue localization and pathogen load; (iv) Predisposing factors for
      infection and factors influencing expression of disease; (v) Carrier state in
      fish; (vi) Diagnostic methods; (vii) Survival in the environment; (viii)
      Permissive temperature range; (ix) Stability of the agent in aquatic animal
      products; (x) Prevalence of infection; and (xi) Affected life stages. Much of the
      biological information presented is relevant to a broad range of risk questions.
      Areas where data are lacking were identified, and the information provided is put
      into context with other aspects that need to be addressed in an IRA.

PMID- 21733136
TI  - Attachment security as a mechanism linking foster care placement to improved
      mental health outcomes in previously institutionalized children.
AB  - BACKGROUND: Children reared in institutions experience elevated rates of
      psychiatric disorders. Inability to form a secure attachment relationship to a
      primary caregiver is posited to be a central mechanism in this association. We
      determined whether the ameliorative effect of a foster care (FC) intervention on
      internalizing disorders in previously institutionalized children was explained by
      the development of secure attachment among children placed in FC. Second we
      evaluated the role of lack of attachment in an institutionalized sample on the
      etiology of internalizing disorders within the context of a randomized trial.
      METHODS: A sample of 136 children (aged 6-30 months) residing in institutions was
      recruited in Bucharest, Romania. Children were randomized to FC (n = 68) or to
      care as usual (CAU; n = 68). Foster parents were recruited, trained, and overseen
      by the investigative team. Attachment security at 42 months was assessed using
      the Strange Situation Procedure, and internalizing disorders at 54 months were
      assessed using the Preschool Age Psychiatric Assessment. RESULTS: Girls in FC had
      fewer internalizing disorders than girls in CAU (OR = 0.17, p = .006). The
      intervention had no effect on internalizing disorders in boys (OR = 0.47, p =
      .150). At 42 months, girls in FC were more likely to have secure attachment than
      girls in CAU (OR = 12.5, p < .001), but no difference was observed in boys (OR =
      2.0, p = .205). Greater attachment security predicted lower rates of
      internalizing disorders in both sexes. Development of attachment security fully
      mediated intervention effects on internalizing disorders in girls. CONCLUSION:
      Placement into FC facilitated the development of secure attachment and prevented
      the onset of internalizing disorders in institutionalized girls. The differential
      effects of FC on attachment security in boys and girls explained gender
      differences in the intervention effects on psychopathology. Findings provide
      evidence for the critical role of disrupted attachment in the etiology of
      internalizing disorders in children exposed to institutionalization.

PMID- 21733137
TI  - Ownership type and team climate in elderly care facilities: the moderating effect
      of stress factors.
AB  - AIMS: This paper is a report of a study examining the association between
      ownership type and perceived team climate among older people care staff. In
      addition, we examined whether work stress factors (time pressure, resident
      related stress, role conflicts and role ambiguity) mediated or moderated the
      above mentioned association. BACKGROUND: There has been a trend towards
      contracting out in older people care facilities in Finland and the number of
      private for-profit firms has increased. Studies suggest that there may be
      differences in employee well-being and quality of care according to the ownership
      type of older people care. METHODS: Cross-sectional survey data was collected
      during the autumn of 2007 from 1084 Finnish female older people care staff aged
      18-69 years were used. Team Climate Inventory was used to measure team climate.
      Ownership type was divided into four categories: for-profit sheltered homes, not
      for-profit sheltered homes, public sheltered homes and not-for-profit nursing
      homes. Analyses of covariance were used to examine the associations. RESULTS:
      Team climate dimensions participative safety, vision and support for innovation
      were higher in not-for-profit organizations (both sheltered homes and nursing
      homes) compared to for-profit sheltered homes and public sheltered homes. Stress
      factors did not account for these associations but acted as moderators in a way
      that in terms of task orientation and participative safety employees working in
      for-profit organizations seemed to be slightly more sensitive to work-related
      stress than others. CONCLUSION: Our results suggest that for-profit organizations
      and public organizations may have difficulties in maintaining their team climate.
      In consequence, these organizations should focus more effort on improving their
      team climate.

PMID- 21733138
TI  - A follow-up evaluation of the impact of the Chief Nursing Officer's review of
      mental health nursing in Mental Health Trusts and Universities in England:
      comparisons of two e-surveys.
AB  - AIMS: This article is a report of a study that aimed to establish a national
      picture of the implementation of Review recommendations over time in both Mental
      Health Trusts and Higher Education Institutions (Universities) in England.
      BACKGROUND: The 2006 Review of Mental Health Nursing in England by the Chief
      Nursing Officer made 17 key recommendations for Mental Health Trusts and
      Universities to improve mental health nursing. This article outlines key findings
      from a national survey of National Health Service Trusts and Universities in
      England with regard to prioritization and progress on implementation of these
      recommendations. METHODS: An e-survey was carried out in 2008-2009 based on the
      Chief Nursing Officer review recommendations and guidance. Participants included
      all Trusts which delivered mental health services (n = 68) and Universities which
      delivered pre-registration mental health nursing education (n = 50) in England.
      RESULTS: There appears to be some evidence that the Chief Nursing Officer review
      of Mental Health Nursing in England continues to be implemented in both Mental
      Health Trusts and Universities. There is variety in levels of implementation, but
      Mental Health Trusts and Universities broadly agree on priority areas.
      CONCLUSIONS: The Chief Nursing Officer review has been influential in focusing
      the care and education of mental health nurses and services in England. There
      appears to be a range of barriers and facilitators which aid the implementation
      of healthcare policy. More attention is required from researchers to enhance and
      evaluate the impact of policy implementation on the quality of care provided.

PMID- 21733139
TI  - Trends in health outcomes for family caregivers of hip-fractured elders during
      the first 12 months after discharge.
AB  - AIM: This article reports on trends in health outcomes for family caregivers of
      hip-fractured patients and the effects of social support on these outcomes.
      BACKGROUND: Little is known about the impact of caregiving on the health outcomes
      of family caregivers of patients with hip fracture. METHOD:   For this
      prospective, correlational study, data were collected from 135 family caregivers
      of hip-fractured elders (2001-2005). Data on health-related quality of life and
      social support were collected from family caregivers at 1, 3, 6 and 12 months
      after discharge of the older hip-fractured patient. FINDINGS: During the 12
      months after the patients' discharge, family caregivers' scores improved
      significantly in role performance-related scales, including bodily pain, social
      function, role limitations due to emotional problems and role limitations due to
      physical problems. However, caregivers' scores for general health and mental
      health were significantly lower at 12 months [59.91 (sd = 24.54) and 65.91 (sd =
      14.36) respectively] than at 1 month after discharge [64.35 (sd = 23.29) and
      67.94 (sd = 18.47) respectively]. The trends for most subscale scores for health
      related quality of life were positively related to perceived availability of
      social support. CONCLUSIONS: Caring for a hip-fractured older family member over
      a sustained period may enhance family caregivers' role performance, but have a
      negative impact on their perceived general health and mental health. These
      results suggest that home care nurses should develop interventions early after
      discharge to assess and improve family caregivers' health perception, mental
      health and social support.

PMID- 21733140
TI  - Self-care agency and perceived health among people using advanced medical
      technology at home.
AB  - AIM: This article reports a study of self-care agency and perceived health in a
      group of people using advanced medical technology at home. BACKGROUND: An
      increasing number of people are using medical technology for self-care. Few
      studies describe daily life in this context at an overriding level, irrespective
      of the specific sort of technology. A connection between self-care, perceived
      health and sense of coherence has previously been implied. METHODS: A
      descriptive, comparative, cross-sectional quantitative design was used. Data were
      collected from a questionnaire during the winter of 2009/2010. The questionnaire
      addressed perceived health and daily life with medical technology. Swedish
      versions of the Appraisal of Self-care Agency scale and the 13-item version of
      Antonovsky's sense of coherence scale were included. RESULTS: The questionnaire
      was answered by 180 adults performing self-care at home involving long-term
      oxygen, a ventilator, or peritoneal- or haemo-dialysis. Health-related and
      technology-related variables in daily life were mostly highly satisfactory.
      Perceived health was rated significantly lower among participants using long-term
      oxygen. Sufficient sense of coherence, knowledge of how to use technology, close
      contact with others and not feeling helpless contributed positively to self-care
      agency. Positive contributing factors for perceived health were being satisfied
      with life, having an active life and not feeling helpless, whereas age was a
      negative factor. CONCLUSION: Daily life is manageable for people in this context.
      Long-term oxygen treatment and advanced age can be regarded as risk factors for
      perceiving ill health.

PMID- 21733141
TI  - Life experiences of security and insecurity among women with chronic heart
      failure.
AB  - AIM: This paper is a report of a study illuminating women's experiences of living
      with chronic heart failure with a focus on feelings of security and insecurity.
      BACKGROUND: To be secure is a basic human need. Although feelings of being
      insecure has been found to be a common problem among people who live with chronic
      heart failure few qualitative studies, particularly among women, have been
      carried out in the field. METHOD: Eight women took part in focus group interviews
      during 2006. The data were analysed using qualitative content analysis. FINDINGS:
      The women's feelings of security include acceptance of the past, everyday life
      and the future, trusting the self and the body despite the disease, not having to
      deal with dependency alone, and faith in care and treatment. The women's feelings
      of insecurity include feeling guilty for being sick and incapacitated, fear of
      living with a frail and failing body, anxiety about growing dependence on others,
      loneliness and death and lack of faith in care and treatment. CONCLUSION: The
      outlook on the past, the present and the view about the future, can be
      fundamental for the quality of life, and the sense of security and insecurity
      among women living with chronic heart failure. To support a sense of security it
      seems essential that nursing staff attempt to understand the women's outlook on
      life and their personal interpretations of living with chronic heart failure.
      This can be crucial for enhancing feelings of security in daily life for these
      women.

PMID- 21733142
TI  - A qualitative analysis of the nutritional requirements of palliative care
      patients.
AB  - BACKGROUND: The National Health Servive (NHS) Quality Improvement Scotland
      developed nutritional Clinical Standards to address the problem of malnutrition
      in hospitals. NHS palliative care units are obliged to incorporate these
      standards into nutritional aspects of care. The nutritional needs of this patient
      population are under-researched. The present study aimed to explore patients'
      views of nutrition, to begin to understand their concerns and to determine
      whether such standards meet the needs of patients in the palliative care setting.
      METHODS: A qualitative study was conducted in 2009 in an NHS Palliative Care
      Unit. Six inpatients were involved in one-to-one interviews, which were
      audiotaped and transcribed verbatim. The transcripts were subject to qualitative
      data analysis in accordance with a previous framework. RESULTS: A recurring theme
      that emerged was that of change and uncertainty. Four main areas subject to
      change were: disease state, symptoms, oral dietary intake and weight. Each change
      could exert control over, or be controlled by, the patient. When patients were
      eventually unable to exert control, they accepted the change, either willingly or
      enforced, thereby unintentionally setting their own targets. CONCLUSIONS: The
      present study enables a deeper understanding of the concerns that palliative care
      patients have regarding their oral dietary intake and weight. Their
      'malnutrition' not only refers to physical malnutrition alone, but also
      incorporates psychological and social 'malnutrition'. When applying standards or
      protocols regarding nutritional care, these wider issues must be taken into
      account to meet patients' nutritional needs.

PMID- 21733143
TI  - Simple nutritional intervention in patients with advanced cancers of the
      gastrointestinal tract, non-small cell lung cancers or mesothelioma and weight
      loss receiving chemotherapy: a randomised controlled trial.
AB  - BACKGROUND: Weight loss in patients with cancer is common and associated with a
      poorer survival and quality of life. Benefits from nutritional interventions are
      unclear. The present study assessed the effect of dietary advice and/or oral
      nutritional supplements on survival, nutritional endpoints and quality of life in
      patients with weight loss receiving palliative chemotherapy for gastrointestinal
      and non-small cell lung cancers or mesothelioma. METHODS: Participants were
      randomly assigned to receive no intervention, dietary advice, a nutritional
      supplement or dietary advice plus supplement before the start of chemotherapy.
      Patients were followed for 1 year. Survival, nutritional status and quality of
      life were assessed. RESULTS: In total, 256 men and 102 women (median age, 66
      years; range 24-88 years) with gastrointestinal (n = 277) and lung (n = 81)
      cancers were recruited. Median (range) follow-up was 6 (0-49) months. One-year
      survival was 38.6% (95% confidence interval 33.3-43.9). No differences in
      survival, weight or quality of life between groups were seen. Patients surviving
      beyond 26 weeks experienced significant weight gain from baseline to 12 weeks,
      although this was independent of nutritional intervention. CONCLUSIONS: Simple
      nutritional interventions did not improve clinical or nutritional outcomes or
      quality of life. Weight gain predicted a longer survival but occurred
      independently of nutritional intervention.

PMID- 21733144
TI  - The development of nonweighed pilot methods for estimating phenylalanine
      exchanges in non-phenylketonuria volunteers.
AB  - BACKGROUND: In children with phenylketonuria (PKU), the daily weighing of the
      phenylalanine allowance from food is advocated. There is a need to develop
      nonweighed methods of measuring dietary phenylalanine, aiming to ease caregiver
      burden and possibly improve dietary adherence. The accuracy of three methods
      (household measures, digital photographs and weighing) for measuring 50-mg
      phenylalanine exchanges for PKU was investigated in a randomised, controlled
      trial. METHODS: There were 51 volunteers (32 females; 19 males; median age:
      34years, range 13-77years), who were all unconnected with PKU. For three
      consecutive days, all volunteers attended a research centre and, each day, were
      randomly allocated a different method (household measures, digital photographs
      and weighing) for phenylalanine exchange measurement. On each day, they measured
      the amount of food equivalent to one 50-mg phenylalanine exchange for 24 common
      foods. All phenylalanine exchange samples (3672 samples) were then reweighed by
      the investigators. RESULTS: No method of measuring 50-mg phenylalanine exchanges
      was accurate when used by volunteers. The median percentages (range) of all food
      samples within 10% of target were only 67% (41-98), 44% (4-96) and 41% (4-98) for
      weighing, household measures and photographs, respectively. The respective median
      (range) of samples within 20% of the target weights were: 96% (51-100) weighing,
      82% (10-100) photographs and 80% (6-100) household measures. No noteworthy
      difference in accuracy was observed between household measures and photographs.
      CONCLUSIONS: Volunteers not associated with PKU could not measure 50-mg
      phenylalanine exchanges accurately using weighing, household measurements or
      photographs. Therefore, it is important to consider developing methods for
      improving accuracy of measurement of 50-mg phenylalanine exchanges in PKU.

PMID- 21733145
TI  - The potential investment impact of improved access to accelerated approval on the
      development of treatments for low prevalence rare diseases.
AB  - BACKGROUND: Over 95% of rare diseases lack treatments despite many successful
      treatment studies in animal models. To improve access to treatments, the
      Accelerated Approval (AA) regulations were implemented allowing the use of
      surrogate endpoints to achieve drug approval and accelerate development of life
      saving therapies. Many rare diseases have not utilized AA due to the difficulty
      in gaining acceptance of novel surrogate endpoints in untreated rare diseases.
      METHODS: To assess the potential impact of improved AA accessibility, we devised
      clinical development programs using proposed clinical or surrogate endpoints for
      fifteen rare disease treatments. RESULTS: We demonstrate that better AA access
      could reduce development costs by approximately 60%, increase investment value,
      and foster development of three times as many rare disease drugs for the same
      investment. CONCLUSION: Our research brings attention to the need for well
      defined and practical qualification criteria for the use of surrogate endpoints
      to allow more access to the AA approval pathway in clinical trials for rare
      diseases.

PMID- 21733146
TI  - Composite lymphoma in the anterior mediastinum: a case report and review of the
      literature.
AB  - We recently encountered an unusual case of Composite lymphoma (CL) in the
      anterior mediastinum arising in a 37-year-old woman who presented initially with
      continuous pain in the right shoulder and chest. The woman had been suffered from
      continuous pain for three months before she went to our department of
      cardiovascular surgery. Chest computed tomography scan revealed the oval space
      occupying lesion of anterior mediastinum. Surgery was performed and the disease
      was diagnosed pathologically as CL which composed of nodular sclerosing Hodgkin
      lymphoma and diffuse large B-cell lymphoma, via hematoxylin-eosin (H&E),
      immunohistochemical staining and in situ hybridization.

PMID- 21733147
TI  - Effect of deferiprone or deferoxamine on right ventricular function in
      thalassemia major patients with myocardial iron overload.
AB  - BACKGROUND: Thalassaemia major (TM) patients need regular blood transfusions that
      lead to accumulation of iron and death from heart failure. Deferiprone has been
      reported to be superior to deferoxamine for the removal of cardiac iron and
      improvement in left ventricular (LV) function but little is known of their
      relative effects on the right ventricle (RV), which is being increasingly
      recognised as an important prognostic factor in cardiomyopathy. Therefore data
      from a prospective randomised controlled trial (RCT) comparing these chelators
      was retrospectively analysed to assess the RV responses to these drugs. METHODS:
      In the RCT, 61 TM patients were randomised to receive either deferiprone or
      deferoxamine monotherapy, and CMR scans for T2* and cardiac function were
      obtained. Data were re-analysed for RV volumes and function at baseline, and
      after 6 and 12 months of treatment. RESULTS: From baseline to 12 months,
      deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p=0.008),
      whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p=0.001). This was
      associated with a 27% increase in T2* (p<0.001) and 3.1% increase in LVEF
      (p<0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL,
      p=0.38), or RVEF (70.0 to 69.9%, p=0.93) whereas the T2* increased by 13%
      (p<0.001), but with no change in LVEF (0.32%; p=0.66). Analysis of between drugs
      treatment effects, showed significant improvements favouring deferiprone with a
      mean effect on RVESV of -1.82 mL (p=0.014) and 1.16% for RVEF (p=0.009). Using
      regression analysis the improvement in RVEF at 12 months was shown to be greater
      in patients with lower baseline EF values (p<0.001), with a significant
      difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p=0.012).
      CONCLUSION: In this retrospective analysis of a prospective RCT, deferiprone
      monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic
      volume. This improvement in the RV volumes and function may contribute to the
      improved cardiac outcomes seen with deferiprone.

PMID- 21733148
TI  - A comparative analysis of DNA methylation across human embryonic stem cell lines.
AB  - BACKGROUND: We performed a comparative analysis of the genome-wide DNA
      methylation profiles from three human embryonic stem cell (HESC) lines. It had
      previously been shown that HESC lines had significantly higher non-CG methylation
      than differentiated cells, and we therefore asked whether these sites were
      conserved across cell lines. RESULTS: We find that heavily methylated non-CG
      sites are strongly conserved, especially when found within the motif TACAG. They
      are enriched in splice sites and are more methylated than other non-CG sites in
      genes. We next studied the relationship between allele-specific expression and
      allele-specific methylation. By combining bisulfite sequencing and whole
      transcriptome shotgun sequencing (RNA-seq) data we identified 1,020 genes that
      show allele-specific expression, and 14% of CG sites genome-wide have allele
      specific methylation. Finally, we asked whether the methylation state of
      transcription factor binding sites affects the binding of transcription factors.
      We identified variations in methylation levels at binding sites and found that
      for several transcription factors the correlation between the methylation at
      binding sites and gene expression is generally stronger than in the neighboring
      sequences. CONCLUSIONS: These results suggest a possible but as yet unknown
      functional role for the highly methylated conserved non-CG sites in the
      regulation of HESCs. We also identified a novel set of genes that are likely
      transcriptionally regulated by methylation in an allele-specific manner. The
      analysis of transcription factor binding sites suggests that the methylation
      state of cis-regulatory elements impacts the ability of factors to bind and
      regulate transcription.

PMID- 21733149
TI  - Treating frailty--a practical guide.
AB  - Frailty is a common syndrome that is associated with vulnerability to poor health
      outcomes. Frail older people have increased risk of morbidity,
      institutionalization and death, resulting in burden to individuals, their
      families, health care services and society. Assessment and treatment of the frail
      individual provide many challenges to clinicians working with older people.
      Despite frailty being increasingly recognized in the literature, there is a
      paucity of direct evidence to guide interventions to reduce frailty. In this
      paper we review methods for identification of frailty in the clinical setting,
      propose a model for assessment of the frail older person and summarize the
      current best evidence for treating the frail older person. We provide an evidence
      based framework that can be used to guide the diagnosis, assessment and treatment
      of frail older people.

PMID- 21733150
TI  - Development of environmental tools for anopheline larval control.
AB  - BACKGROUND: Malaria mosquitoes spend a considerable part of their life in the
      aquatic stage, rendering them vulnerable to interventions directed to aquatic
      habitats. Recent successes of mosquito larval control have been reported using
      environmental and biological tools. Here, we report the effects of shading by
      plants and biological control agents on the development and survival of
      anopheline and culicine mosquito larvae in man-made natural habitats in western
      Kenya. Trials consisted of environmental manipulation using locally available
      plants, the introduction of predatory fish and/or the use of Bacillus
      thuringiensis var. israelensis (Bti) in various combinations. RESULTS: Man-made
      habitats provided with shade from different crop species produced significantly
      fewer larvae than those without shade especially for the malaria vector Anopheles
      gambiae. Larval control of the African malaria mosquito An. gambiae and other
      mosquito species was effective in habitats where both predatory fish and Bti were
      applied, than where the two biological control agents were administered
      independently. CONCLUSION: We conclude that integration of environmental
      management techniques using shade-providing plants and predatory fish and/or Bti
      are effective and sustainable tools for the control of malaria and other mosquito
      borne disease vectors.

PMID- 21733151
TI  - Suicide in the Philippines: time trend analysis (1974-2005) and literature
      review.
AB  - BACKGROUND: Suicide prevention is given a low priority in many Western Pacific
      countries due to competing health problems, stigma and poor understanding of its
      incidence and aetiology. Little is known about the epidemiology of suicide and
      suicidal behaviour in the Philippines and although its incidence is reported to
      be low, there is likely to be under-reporting because of its non-acceptance by
      the Catholic Church and the associated stigma to the family. This study aims to
      investigate trends in the incidence of suicide in the Philippines, assess
      possible underreporting and provide information on the methods used and the
      reasons for suicide. METHODS: Data for suicide deaths occurring between 1974 and
      2005 were obtained from Philippine Health Statistics. Age- and sex-specific
      trends were examined graphically. Underreporting was investigated by comparing
      trends in suicides, accidents and deaths of undetermined intent. To provide a
      fuller picture of suicide in the Philippines, a comprehensive search for
      published papers, theses and reports on the epidemiology of suicide in the
      Philippines was undertaken. RESULTS: The incidence of suicide in males increased
      from 0.23 to 3.59 per 100,000 between 1984 and 2005. Similarly, rates rose from
      0.12 to 1.09 per 100,000 in females. Amongst females, suicide rates were highest
      in 15-24 year olds, whilst in males rates were similar in all age groups
      throughout the study period. The most commonly used methods of suicide were
      hanging, shooting and organophosphate ingestion. In non-fatal attempts, the most
      common methods used were ingestion of drugs, specifically isoniazid and
      paracetamol, or organophosphate ingestion. Family and relationship problems were
      the most common precipitants. While rates were lower compared to other countries,
      there is suggestive evidence of underreporting and misclassification to
      undetermined injury. Recent increases may reflect either true increase or better
      reporting of suicides. CONCLUSIONS: While suicide rates are low in the
      Philippines, increases in incidence and relatively high rates in adolescents and
      young adults point to the importance of focused suicide prevention programs.
      Improving data quality and better reporting of suicide deaths is likewise
      imperative to inform and evaluate prevention strategies.

PMID- 21733152
TI  - Functional exchangeability of the nuclear localization signal (NLS) of capsid
      protein between PCV1 and PCV2 in vitro: Implications for the role of NLS in viral
      replication.
AB  - BACKGROUND: Porcine circovirus type 2 (PCV2) is believed to be the primary
      causative agent of postweaning multisystemic wasting syndrome (PMWS). It is
      supposed that capsid protein of PCV may contribute to replication control via
      interaction between Cap and Rep in the nucleoplasm. In this study, we described
      the construction and in vitro characterization of NLS-exchanged PCV DNA clones
      based on a PMWS-associated PCV2b isolate from China to determine the role of ORF2
      NLS in PCV replication. RESULTS: The PCV1, PCV2, PCV2-NLS1 and PCV1-NLS2 DNA
      clone were generated by ligating a copy of respective genome in tandem with a
      partial duplication. The PCV2-NLS1 and PCV1-NLS2 DNA clone contained a chimeric
      genome in which the ORF2 NLS was exchanged. The four DNA clones were all
      confirmed to be infectious in vitro when transfected into PK-15 cells, as PCV
      capsid protein were expressed in approximately 10-20% of the transfected cells.
      The in vitro growth characteristics of the DNA clones were then determined and
      compared. All the recovered progeny viruses gave rise to increasing infectious
      titers during passages and were genetically stable by genomic sequencing. The
      chimeric PCV1-NLS2 and PCV2-NLS1 viruses had the final titers of about 104.2 and
      103.8 TCID50/ml, which were significantly lower than that of PCV1 and PCV2 (105.6
      and 105.0 TCID50/ml, respectively). When the ORF2 NLS exchanged, the mutant PCV2
      (PCV2-NLS1) still replicated less efficiently and showed lower infectious titer
      than did PCV1 mutant (PCV1-NLS2), which was consistent with the distinction
      between wild type PCV1 and PCV2. CONCLUSIONS: Recovery of the chimeiric PCV1-NLS2
      and PCV2-NLS1 progeny viruses indicate that the nuclear localization signal
      sequence of capsid protein are functionally exchangeable between PCV1 and PCV2
      with respect to the role of nuclear importing and propagation. The findings also
      reveal that ORF2 NLS play an accessory role in the replication of PCV. However,
      we found that ORF2 NLS was not responsible for the distinction of in vitro growth
      characteristic between PCV1 and PCV2. Further studies are required to determine
      the in vivo viral replication and pathogenicity of the NLS chimeric DNA clones.

PMID- 21733153
TI  - Facile synthesis of concentrated gold nanoparticles with low size-distribution in
      water: temperature and pH controls.
AB  - The citrate reduction method for the synthesis of gold nanoparticles (GNPs) has
      known advantages but usually provides the products with low nanoparticle
      concentration and limits its application. Herein, we report a facile method to
      synthesize GNPs from concentrated chloroauric acid (2.5 mM) via adding sodium
      hydroxide and controlling the temperature. It was found that adding a proper
      amount of sodium hydroxide can produce uniform concentrated GNPs with low size
      distribution; otherwise, the largely distributed nanoparticles or instable
      colloids were obtained. The low reaction temperature is helpful to control the
      nanoparticle formation rate, and uniform GNPs can be obtained in presence of
      optimized NaOH concentrations. The pH values of the obtained uniform GNPs were
      found to be very near to neutral, and the pH influence on the particle size
      distribution may reveal the different formation mechanism of GNPs at high or low
      pH condition. Moreover, this modified synthesis method can save more than 90%
      energy in the heating step. Such environmental-friendly synthesis method for gold
      nanoparticles may have a great potential in large-scale manufacturing for
      commercial and industrial demand.

PMID- 21733154
TI  - A firearm bullet lodged into the thoracic spinal canal without vertebral bone
      destruction: a case report.
AB  - INTRODUCTION: Firearm injuries account for 13% to 17% of all spinal cord
      injuries, and are generally caused during warfare or assault with intent to kill.
      Spinal cord injuries caused by firearms are usually observed in patients aged 15
      to 34 years old, and are especially common among men. CASE PRESENTATION: We
      report the case of a 28-year-old Iraqi man who was referred to our radiology
      department with lower limb paraplegia secondary to a gunshot wound. We performed
      64-slice computerized tomography with two-dimensional and three-dimensional
      reconstruction of the thoracolumbar spine. On the two-dimensional and three
      dimensional reconstructed axial images of the thoracolumbar spine, an intra
      canalicular bullet nucleus was found at the mid-spinal cord at the T8 level, with
      no evidence of vertebral bone destruction. CONCLUSIONS: To the best of our
      knowledge, there is only one previous report in the literature describing a case
      of a bullet nucleus lodged into the inferior epidural spinal canal without
      destruction of the vertebral bone. With the rise of violence worldwide the
      incidence of gunshot injuries continues to increase, and, thus, it is essential
      for radiologists to have a clear understanding of gunshot injuries and the
      findings on radiographic images.

PMID- 21733155
TI  - Genome sequence and global sequence variation map with 5.5 million SNPs in
      Chinese rhesus macaque.
AB  - BACKGROUND: Rhesus macaque (Macaca mulatta) is the most widely used nonhuman
      primate animal in biomedical research. A global map of genetic variations in
      rhesus macaque is valuable for both evolutionary and functional studies. RESULTS:
      Using next-generation sequencing technology, we sequenced a Chinese rhesus
      macaque genome with 11.56-fold coverage. In total, 96% of the reference Indian
      macaque genome was covered by at least one read, and we identified 2.56 million
      homozygous and 2.94 million heterozygous SNPs. We also detected a total of
      125,150 structural variations, of which 123,610 were deletions with a median
      length of 184 bp (ranging from 25 bp to 10 kb); 63% of these deletions were
      located in intergenic regions and 35% in intronic regions. We further annotated
      5,187 and 962 nonsynonymous SNPs to the macaque orthologs of human disease and
      drug-target genes, respectively. Finally, we set up a genome-wide genetic
      variation database with the use of Gbrowse. CONCLUSIONS: Genome sequencing and
      construction of a global sequence variation map in Chinese rhesus macaque with
      the concomitant database provide applicable resources for evolutionary and
      biomedical research.

PMID- 21733156
TI  - Improving the efficiency of feed utilization in poultry by selection. 1. Genetic
      parameters of anatomy of the gastro-intestinal tract and digestive efficiency.
AB  - BACKGROUND: Feed costs represent about 70% of the costs of raising broilers. The
      main way to decrease these costs is to improve feed efficiency by modification of
      diet formulation, but one other possibility would be to use genetic selection.
      Understanding the genetic architecture of the gastro-intestinal tract (GIT) and
      the impact of the selection criterion on the GIT would be of particular interest.
      We therefore studied the genetic parameters of AMEn (Apparent metabolisable
      energy corrected for zero nitrogen balance), feed efficiency, and GIT traits in
      chickens.Genetic parameters were estimated for 630 broiler chickens of the eighth
      generation of a divergent selection experiment on AMEn. Birds were reared until
      23 d of age and fed a wheat-based diet. The traits measured were body weight
      (BW), feed conversion ratio (FCR), AMEn, weights of crop, liver, gizzard and
      proventriculus, and weight, length and density of the duodenum, jejunum and
      ileum. RESULTS: The heritability estimates of BW, FCR and AMEn were moderate. The
      heritability estimates were higher for the GIT characteristics except for the
      weights of the proventriculus and liver. Gizzard weight was negatively correlated
      with density (weight to length ratio) of duodenum, jejunum and ileum.
      Proventriculus and gizzard weights were more strongly correlated with AMEn than
      with FCR, which was not the case for intestine weight and density. CONCLUSIONS:
      GIT traits were largely dependent on genetics and that selecting on AMEn or FCR
      would modify them. Phenotypic observations carried out in the divergent lines
      selected on AMEn were consistent with estimated genetic correlations between AMEn
      and GIT traits.

PMID- 21733157
TI  - Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging
      rats.
AB  - BACKGROUND: GH and IGFs serum levels decline with age. Age-related changes appear
      to be associated to decreases in these anabolic hormones. We have previously
      demonstrated that IGF-I replacement therapy improves insulin resistance, lipid
      metabolism and reduces oxidative damage (in brain and liver) in aging rats. Using
      the same experimental model, the aim of this work was to study whether the
      exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in
      aging rats. METHODS: Three experimental groups were included in this study: young
      healthy controls (yCO, 17 weeks old); untreated old rats (O, 103 weeks old); and
      aging rats treated with IGF-II (O+IGF-II, 2 MUg * 100 g body weight-1 * day-1)
      for 30 days. Analytical parameters were determined in serum by routine laboratory
      methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel,
      Switzerland). Serum levels of hormones (testosterone, IGF-I and insulin) were
      assessed by RIA. Serum Total Antioxidant Status was evaluated using a
      colorimetric assay. Mitochondrial membrane potential was evaluated using
      rhodamine 123 dye (adding different substrates to determine the different
      states). ATP synthesis in isolated mitochondria was determined by an enzymatic
      method. RESULTS: Compared with young controls, untreated old rats showed a
      reduction of IGF-I and testosterone levels with a decrease of serum total
      antioxidant status (TAS). IGF-II therapy improved serum antioxidant capability
      without modifying testosterone and IGF-I circulating concentrations. In addition,
      IGF-II treatment reduced oxidative damage in brain and liver, improving
      antioxidant enzyme activities and mitochondrial function. IGF-II was also able to
      reduce cholesterol and triglycerides levels increasing free fatty acids
      concentrations. CONCLUSIONS: We demonstrate that low doses of IGF-II induce
      hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial
      function, without affecting testosterone and IGF-I levels.

PMID- 21733158
TI  - An organogenesis network-based comparative transcriptome analysis for
      understanding early human development in vivo and in vitro.
AB  - BACKGROUND: Integrated networks hold great promise in a variety of contexts. In a
      recent study, we have combined expression and interaction data to identify a
      putative network underlying early human organogenesis that contains two modules,
      the stemness-relevant module (hStemModule) and the differentiation-relevant
      module (hDiffModule). However, owing to its hypothetical nature, it remains
      unclear whether this network allows for comparative transcriptome analysis to
      advance our understanding of early human development, both in vivo and in vitro.
      RESULTS: Based on this integrated network, we here report comparisons with the
      context-dependent transcriptome data from a variety of sources. By viewing the
      network and its two modules as gene sets and conducting gene set enrichment
      analysis, we demonstrate the network's utility as a quantitative monitor of the
      stem potential versus the differentiation potential. During early human
      organogenesis, the hStemModule reflects the generality of a gradual loss of the
      stem potential. The hDiffModule indicates the stage-specific differentiation
      potential and is therefore not suitable for depicting an extended developmental
      window. Processing of cultured cells of different types further revealed that the
      hStemModule is a general indicator that distinguishes different cell types in
      terms of their stem potential. In contrast, the hDiffModule cannot distinguish
      between differentiated cells of different types but is able to predict
      differences in the differentiation potential of pluripotent cells of different
      origins. We also observed a significant positive correlation between each of
      these two modules and early embryoid bodies (EBs), which are used as in vitro
      differentiation models. Despite this, the network-oriented comparisons showed
      considerable differences between the developing embryos and the EBs that were
      cultured in vitro over time to try to mimic in vivo processes. CONCLUSIONS: We
      strongly recommend the use of these two modules either when pluripotent cell
      types of different origins are involved or when the comparisons made are
      constrained to the in vivo embryos during early human organogenesis (and an
      equivalent in vitro differentiation models). Network-based comparative
      transcriptome analysis will contribute to an increase in knowledge about human
      embryogenesis, particularly when only transcriptome data are currently available.
      These advances will add an extra dimension to network applications.

PMID- 21733159
TI  - Yersinia enterocolitica palearctica serobiotype O:3/4--a successful group of
      emerging zoonotic pathogens.
AB  - BACKGROUND: High-pathogenic Y. enterocolitica ssp. enterocolitica caused several
      human outbreaks in Northern America. In contrast, low pathogenic Y.
      enterocolitica ssp. palearctica serobiotype O:3/4 is responsible for sporadic
      cases worldwide with asymptomatic pigs being the main source of infection.
      Genomes of three Y. enterocolitica ssp. palearctica serobiotype O:3/4 human
      isolates (including the completely sequenced Y11 German DSMZ type strain) were
      compared to the high-pathogenic Y. enterocolitica ssp. enterocolitica 8081 O:8/1B
      to address the peculiarities of the O:3/4 group. RESULTS: Most high-pathogenicity
      associated determinants of Y. enterocolitica ssp. enterocolitica (like the High
      Pathogenicity Island, yts1 type 2 and ysa type 3 secretion systems) are absent in
      Y. enterocolitica ssp. palearctica serobiotype O:3/4 genomes. On the other hand
      they possess alternative putative virulence and fitness factors, such as a
      different ysp type 3 secretion system, an RtxA-like and insecticidal toxins, and
      a N-acetyl-galactosamine (GalNAc) PTS system (aga-operon). Horizontal acquisition
      of two prophages and a tRNA-Asn-associated GIYep-01 genomic island might also
      influence the Y. enterocolitica ssp. palearctica serobiotype O:3/4
      pathoadaptation. We demonstrated recombination activity of the PhiYep-3 prophage
      and the GIYep-01 island and the ability of the aga-operon to support the growth
      of the Y. enterocolitica ssp. enterocolitica O:8/1B on GalNAc. CONCLUSIONS: Y.
      enterocolitica ssp. palearctica serobiotype O:3/4 experienced a shift to an
      alternative patchwork of virulence and fitness determinants that might play a
      significant role in its host pathoadaptation and successful worldwide
      dissemination.

PMID- 21733160
TI  - Understanding the relationship between the perceived characteristics of clinical
      practice guidelines and their uptake: protocol for a realist review.
AB  - BACKGROUND: Clinical practice guidelines have the potential to facilitate the
      implementation of evidence into practice, support clinical decision making,
      specify beneficial therapeutic approaches, and influence public policy. However,
      these potential benefits have not been consistently achieved. The limited impact
      of guidelines can be attributed to organisational constraints, the complexity of
      the guidelines, and the lack of usability testing or end-user involvement in
      their development. Implementability has been referred to as the perceived
      characteristics of guidelines that predict the relative ease of their
      implementation at the clinical level, but this concept is as yet poorly defined.
      The objective of our study is to identify guideline attributes that affect uptake
      in practice by considering evidence from four disciplines (medicine, psychology,
      management, human factors engineering) to determine the relationship between the
      perceived characteristics of recommendations and their uptake and to develop a
      framework of implementability. METHODS: A realist-review approach to knowledge
      synthesis will be used to understand attributes of guidelines (e.g., its text and
      content) and how changing these elements might impact clinical practice and
      clinical decision making. It also allows for the exploration of 'what works for
      whom, in what circumstances, and in what respects'. The realist review will be
      structured according to Pawson's five practical steps in realist reviews: (1)
      clarifying the scope of the review, (2) determining the search strategy, (3)
      ensuring proper article selection and study quality assessment, (4) extracting
      and organising data, and (5) synthesising the evidence and drawing conclusions.
      Data will be synthesised according to a two-stage analysis: (1) we will extract
      and define all relevant guideline attributes from the different disciplines, then
      create a shortlist of unique attributes and investigate their relationships with
      uptake, and (2) we will compare and contrast the attributes and guideline uptake
      within each and between the four disciplines to create a robust framework of
      implementability. DISCUSSION: Creating guidelines that are designed to maximise
      uptake may be a potentially effective and inexpensive way of increasing their
      impact. However, this is best achieved by a comprehensive framework to inform the
      design of guidelines drawing on a range of disciplines that study behaviour
      change. This study will use a customised realist-review approach to synthesising
      the literature to better understand and operationalise a complex and under
      theorised concept.

PMID- 21733161
TI  - A clinical pathway for community-acquired pneumonia: an observational cohort
      study.
AB  - BACKGROUND: Six hospitals instituted a voluntary, system-wide, pathway for
      community acquired pneumonia (CAP). We proposed this study to determine the
      impact of pathway antibiotics on patient survival, hospital length of stay (LOS),
      and total hospital cost. METHODS: Data were collected for adults from six U.S.
      hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and
      medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts
      were assigned according to antibiotics received within 48 hours of admission.
      Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000
      mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90
      day mortality, hospital LOS, total hospital cost, and total pharmacy cost.
      RESULTS: Overall, 792 patients met study criteria. Of these, 505 (64%) received
      pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted
      means and p-values were derived from Least Squares regression models that
      included Pneumonia Severity Index risk class, patient age, heart failure, chronic
      obstructive pulmonary disease, and admitting hospital as covariates. After
      adjustment, patients who received pathway antibiotics experienced lower adjusted
      90-day mortality (p = 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, p <
      0.01), lower mean hospital costs ($2,485 vs. $3,281, p = 0.02), and similar mean
      pharmacy costs ($356 vs. $442, p = 0.11). CONCLUSIONS: Pathway antibiotics were
      associated with improved patient survival, hospital LOS, and total hospital cost
      for patients admitted to the hospital with CAP.

PMID- 21733162
TI  - S-nitrosoglutathione reduces oxidative injury and promotes mechanisms of
      neurorepair following traumatic brain injury in rats.
AB  - BACKGROUND: Traumatic brain injury (TBI) induces primary and secondary damage in
      both the endothelium and the brain parenchyma, collectively termed the
      neurovascular unit. While neurons die quickly by necrosis, a vicious cycle of
      secondary injury in endothelial cells exacerbates the initial injury in the
      neurovascular unit following TBI. In activated endothelial cells, excessive
      superoxide reacts with nitric oxide (NO) to form peroxynitrite. Peroxynitrite has
      been implicated in blood brain barrier (BBB) leakage, altered metabolic function,
      and neurobehavioral impairment. S-nitrosoglutathione (GSNO), a nitrosylation
      based signaling molecule, was reported not only to reduce brain levels of
      peroxynitrite and oxidative metabolites but also to improve neurological function
      in TBI, stroke, and spinal cord injury. Therefore, we investigated whether GSNO
      promotes the neurorepair process by reducing the levels of peroxynitrite and the
      degree of oxidative injury. METHODS: TBI was induced by controlled cortical
      impact (CCI) in adult male rats. GSNO or 3-Morpholino-sydnonimine (SIN-1) (50
      MUg/kg body weight) was administered orally two hours following CCI. The same
      dose was repeated daily until endpoints. GSNO-treated (GSNO group) or SIN-1
      treated (SIN-1 group) injured animals were compared with vehicle-treated injured
      animals (TBI group) and vehicle-treated sham-operated animals (Sham group) in
      terms of peroxynitrite, NO, glutathione (GSH), lipid peroxidation, blood brain
      barrier (BBB) leakage, edema, inflammation, tissue structure, axon/myelin
      integrity, and neurotrophic factors. RESULTS: SIN-1 treatment of TBI increased
      whereas GSNO treatment decreased peroxynitrite, lipid peroxides/aldehydes, BBB
      leakage, inflammation and edema in a short-term treatment (4-48 hours). GSNO also
      reduced brain infarctions and enhanced the levels of NO and GSH. In a long-term
      treatment (14 days), GSNO protected axonal integrity, maintained myelin levels,
      promoted synaptic plasticity, and enhanced the expression of neurotrophic
      factors. CONCLUSION: Our findings indicate the participation of peroxynitrite in
      the pathobiology of TBI. GSNO treatment of TBI not only reduces peroxynitrite but
      also protects the integrity of the neurovascular unit, indicating that GSNO
      blunts the deleterious effects of peroxynitrite. A long-term treatment of TBI
      with the same low dose of GSNO promotes synaptic plasticity and enhances the
      expression of neurotrophic factors. These results support that GSNO reduces the
      levels of oxidative metabolites, protects the neurovascular unit, and promotes
      neurorepair mechanisms in TBI.

PMID- 21733163
TI  - Investigating the global genomic diversity of Escherichia coli using a multi
      genome DNA microarray platform with novel gene prediction strategies.
AB  - BACKGROUND: The gene content of a diverse group of 183 unique Escherichia coli
      and Shigella isolates was determined using the Affymetrix GeneChip(r) E. coli
      Genome 2.0 Array, originally designed for transcriptome analysis, as a genotyping
      tool. The probe set design utilized by this array provided the opportunity to
      determine the gene content of each strain very accurately and reliably. This
      array constitutes 10,112 independent genes representing four individual E. coli
      genomes, therefore providing the ability to survey genes of several different
      pathogen types. The entire ECOR collection, 80 EHEC-like isolates, and a diverse
      set of isolates from our FDA strain repository were included in our analysis.
      RESULTS: From this study we were able to define sets of genes that correspond to,
      and therefore define, the EHEC pathogen type. Furthermore, our sampling of 63
      unique strains of O157:H7 showed the ability of this array to discriminate
      between closely related strains. We found that individual strains of O157:H7
      differed, on average, by 197 probe sets. Finally, we describe an analysis method
      that utilizes the power of the probe sets to determine accurately the
      presence/absence of each gene represented on this array. CONCLUSIONS: These
      elements provide insights into understanding the microbial diversity that exists
      within extant E. coli populations. Moreover, these data demonstrate that this
      novel microarray-based analysis is a powerful tool in the field of molecular
      epidemiology and the newly emerging field of microbial forensics.

PMID- 21733164
TI  - Fibroblast growth factor 2 orchestrates angiogenic networking in non-GIST STS
      patients.
AB  - BACKGROUND: Non-gastrointestinal stromal tumor soft-tissue sarcomas (non-GIST
      STSs) constitute a heterogeneous group of tumors with poor prognosis. Fibroblast
      growth factor 2 (FGF2) and fibroblast growth factor receptor-1 (FGFR-1), in close
      interplay with platelet-derived growth factor-B (PDGF-B) and vascular endothelial
      growth factor receptor-3 (VEGFR-3), are strongly involved in angiogenesis. This
      study investigates the prognostic impact of FGF2 and FGFR-1 and explores the
      impact of their co-expression with PDGF-B and VEGFR-3 in widely resected tumors
      from non-GIST STS patients. METHODS: Tumor samples from 108 non-GIST STS patients
      were obtained and tissue microarrays were constructed for each specimen.
      Immunohistochemistry was used to evaluate the expressions of FGF-2, FGFR-1, PDGF
      B and VEGFR-3. RESULTS: In the multivariate analysis, high expression of FGF2 (P
      = 0.024, HR = 2.2, 95% CI 1.1-4.4) and the co-expressions of FGF2 & PDGF-B
      (overall; P = 0.007, intermediate; P = 0.013, HR = 3.6, 95% CI = 1.3-9.7, high; P
      = 0.002, HR = 6.0, 95% CI = 2.0-18.1) and FGF2 & VEGFR-3 (overall; P = 0.050,
      intermediate; P = 0.058, HR = 2.0, 95% CI = 0.98-4.1, high; P = 0.028, HR = 2.6,
      95% CI = 1.1-6.0) were significant independent prognostic indicators of poor
      disease-specific survival. CONCLUSION: FGF2, alone or in co-expression with PDGF
      B and VEGFR-3, is a significant independent negative prognosticator in widely
      resected non-GIST STS patients.

PMID- 21733165
TI  - Increased risk of miscarriage among women experiencing physical or sexual
      intimate partner violence during pregnancy in Guatemala City, Guatemala: cross
      sectional study.
AB  - BACKGROUND: Violence against women by their male intimate partners (IPV) during
      pregnancy may lead to negative pregnancy outcomes. We examined the role of IPV as
      a potential risk factor for miscarriage in Guatemala. Our objectives were: (1) To
      describe the magnitude and pattern of verbal, physical and sexual violence by
      male intimate partners in the last 12 months (IPV) in a sample of pregnant
      Guatemalans; (2) To evaluate the influence of physical or sexual IPV on
      miscarriage as a pregnancy outcome. METHODS: All pregnant women reporting to the
      maternity of a major tertiary care public hospital in Guatemala City from June
      1st to September 30th, 2006 were invited to participate in this cross-sectional
      study. The admitting physician assessed occurrence of miscarriage, defined as
      involuntary pregnancy loss up to and including 28 weeks gestation. Data on IPV,
      social and demographic characteristics, risk behaviours, and medical history were
      collected by interviewer-administered questionnaire. Laboratory testing was
      performed for HIV and syphilis. The relationship between IPV and miscarriage was
      assessed through multivariable logistic regression. RESULTS: IPV affected 18% of
      the 1897 pregnant Guatemalan women aged 15-47 in this sample. Verbal IPV was most
      common (16%), followed by physical (10%) and sexual (3%) victimisation. Different
      forms of IPV were often co-prevalent. Miscarriage was experienced by 10% of the
      sample (n = 190). After adjustment for potentially confounding factors, physical
      or sexual victimisation by a male intimate partner in the last 12 months was
      significantly associated with miscarriage (ORadj 1.1 to 2.8). Results were robust
      under a range of analytic assumptions. CONCLUSIONS: Physical and sexual IPV is
      associated with miscarriage in this Guatemalan facility-based sample. Results
      cohere well with findings from population-based surveys. IPV should be recognised
      as a potential cause of miscarriage. Reproductive health services should be used
      to screen for spousal violence and link to assistance.

PMID- 21733166
TI  - INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence
      Gives Added Therapeutic Effect?): study protocol for a mixed methods study to
      assess the feasibility of a future randomised controlled trial of the clinical
      utility of invasive urodynamic testing.
AB  - BACKGROUND: Urinary incontinence is an important health problem to the individual
      sufferer and to health services. Stress and stress predominant mixed urinary
      incontinence are increasingly managed by surgery due to advances in surgical
      techniques. Despite the lack of evidence for its clinical utility, most
      clinicians undertake invasive urodynamic testing (IUT) to confirm a functional
      diagnosis of urodynamic stress incontinence before offering surgery for this
      condition. IUT is expensive, embarrassing and uncomfortable for women and carries
      a small risk. Recent systematic reviews have confirmed the lack of high quality
      evidence of effectiveness.The aim of this pilot study is to test the feasibility
      of a future definitive randomised control trial that would address whether IUT
      alters treatment decisions and treatment outcome in these women and would test
      its clinical and cost effectiveness. METHODS/DESIGN: This is a mixed methods
      pragmatic multicentre feasibility pilot study with four components:-(a) A
      multicentre, external pilot randomised trial comparing basic clinical assessment
      with non-invasive tests and IUT. The outcome measures are rates of recruitment,
      randomisation and data completion. Data will be used to estimate sample size
      necessary for the definitive trial.(b) Qualitative interviews of a purposively
      sampled sub-set of women eligible for the pilot trial will explore willingness to
      participate, be randomised and their overall trial experience.(c) A national
      survey of clinicians to determine their views of IUT in this context, the main
      outcome being their willingness to randomise patients into the definitive
      trial.(d) Qualitative interviews of a purposively sampled group of these
      clinicians will explore whether and how they use IUT to inform their decisions.
      DISCUSSION: The pilot trial will provide evidence of feasibility and
      acceptability and therefore inform the decision whether to proceed to the
      definitive trial. Results will inform the design and conduct of the definitive
      trial and ensure its effectiveness in achieving its research aim. TRIAL
      REGISTRATION NUMBER: Current Controlled Trials ISRCTN71327395 assigned 7th June
      2010.

PMID- 21733167
TI  - Brain iron accumulation in unexplained fetal and infant death victims with smoker
      mothers--the possible involvement of maternal methemoglobinemia.
AB  - BACKGROUND: Iron is involved in important vital functions as an essential
      component of the oxygen-transporting heme mechanism. In this study we aimed to
      evaluate whether oxidative metabolites from maternal cigarette smoke could affect
      iron homeostasis in the brain of victims of sudden unexplained fetal and infant
      death, maybe through the induction of maternal hemoglobin damage, such as in case
      of methemoglobinemia. METHODS: Histochemical investigations by Prussian blue
      reaction were made on brain nonheme ferric iron deposits, gaining detailed data
      on their localization in the brainstem and cerebellum of victims of sudden death
      and controls. The Gless and Marsland's modification of Bielschowsky's was used to
      identify neuronal cell bodies and neurofilaments. RESULTS: Our approach
      highlighted accumulations of blue granulations, indicative of iron positive
      reactions, in the brainstem and cerebellum of 33% of victims of sudden death and
      in none of the control group. The modified Bielschowsky's method confirmed that
      the cells with iron accumulations were neuronal cells. CONCLUSIONS: We propose
      that the free iron deposition in the brain of sudden fetal and infant death
      victims could be a catabolic product of maternal methemoglobinemia, a biomarker
      of oxidative stress likely due to nicotine absorption.

PMID- 21733168
TI  - Spontaneous traumatic macular hole closure in a 50-year-old woman: a case report.
AB  - INTRODUCTION: Traumatic macular holes (TMH) are well-known complications of
      ocular contusion injury. Spontaneous closure occurs in approximately 50% of
      cases, but rarely after the age of thirty. We report a case of spontaneous
      closure of a full thickness macular hole due to a blunt trauma and we suggest
      possible mechanisms for this closure. CASE PRESENTATION: A 50-year-old Greek
      woman was referred with a history of reduced best-corrected visual acuity after
      blunt trauma to her right eye. Diagnosis was based on fundoscopic, optical
      coherence tomography as well as fluorescein angiography findings with follow-up
      visits at two days, 20 days and five months. Fundoscopy revealed a full-thickness
      TMH with a minor sub-retinal hemorrhage and posterior vitreous detachment. The
      presence of a coagulum in the TMH base was observed. Subsequently, TMH closure
      was observed. CONCLUSION: The clot in the TMH base, potentially a hemorrhage by
      product containing a significant quantity of platelets, may have simulated the
      clot observed after autologous serum use, thus facilitating a similar effect.
      This may have stimulated glial cell migration and proliferation, thus
      contributing to spontaneous hole closure.

PMID- 21733169
TI  - Delayed diagnosis of oral squamous cell carcinoma: a case series.
AB  - INTRODUCTION: In malign neoplasms, oral cancer is one of the important causes of
      mortality and morbidity. Squamous cell carcinoma is the most common form of oral
      cancers in adults and is related to risk factors such as smoking and alcohol
      consumption. CASE PRESENTATION: In this article, we present three case reports of
      oral squamous cell carcinomas with delayed diagnosis. The first patient was a 52
      year-old Turkish man, the second patient was a 61-year-old Turkish man and the
      third patient was a 60-year-old Turkish woman. All were referred to the Ankara
      University Faculty of Dentistry with pain, swelling and various complaints in
      their jaws. CONCLUSION: Early diagnosis is of vital importance for the prognosis
      of the patients with oral squamous cell carcinomas. For this reason, dentists
      play a crucial role in the early detection and prevention of oral cancers.

PMID- 21733170
TI  - Trends in total and cause-specific mortality by marital status among elderly
      Norwegian men and women.
AB  - BACKGROUND: Previous research has shown large and increasing relative differences
      in mortality by marital status in several countries, but few studies have
      considered trends in cause-specific mortality by marital status among elderly
      people. METHODS: The author uses discrete-time hazard regression and register
      data covering the entire Norwegian population to analyze how associations between
      marital status and several causes of death have changed for men and women of age
      75-89 from 1971-2007. Educational level, region of residence and centrality are
      included as control variables. There are 804 243 deaths during the 11 102 306
      person-years of follow-up. RESULTS: Relative to married persons, those who are
      never married, divorced or widowed have significantly higher mortality for most
      causes of death. The odds of death are highest for divorcees, followed by never
      married and widowed. Moreover, the excess mortality among the non-married is
      higher for men than for women, at least in the beginning of the time period.
      Relative differences in mortality by marital status have increased from 1971
      2007. In particular, the excess mortality of the never married women and, to a
      lesser extent, men has been rising. The widening of the marital status
      differentials is most pronounced for mortality resulting from circulatory
      diseases, respiratory diseases (women), other diseases and external deaths
      (women). Differences in cancer mortality by marital status have been stable over
      time. CONCLUSIONS: Those who are married may have lower mortality because of
      protective effects of marriage or selection of healthy individuals into marriage,
      and the importance of such mechanisms may have changed over time. However, with
      the available data it is not possible to identify the mechanisms responsible for
      the increasing relative differences in mortality by marital status in Norway.

PMID- 21733171
TI  - Genome-wide SNP discovery in tetraploid alfalfa using 454 sequencing and high
      resolution melting analysis.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common type of
      sequence variation among plants and are often functionally important. We describe
      the use of 454 technology and high resolution melting analysis (HRM) for high
      throughput SNP discovery in tetraploid alfalfa (Medicago sativa L.), a species
      with high economic value but limited genomic resources. RESULTS: The alfalfa
      genotypes selected from M. sativa subsp. sativa var. 'Chilean' and M. sativa
      subsp. falcata var. 'Wisfal', which differ in water stress sensitivity, were used
      to prepare cDNA from tissue of clonally-propagated plants grown under either well
      watered or water-stressed conditions, and then pooled for 454 sequencing. Based
      on 125.2 Mb of raw sequence, a total of 54,216 unique sequences were obtained
      including 24,144 tentative consensus (TCs) sequences and 30,072 singletons,
      ranging from 100 bp to 6,662 bp in length, with an average length of 541 bp. We
      identified 40,661 candidate SNPs distributed throughout the genome. A sample of
      candidate SNPs were evaluated and validated using high resolution melting (HRM)
      analysis. A total of 3,491 TCs harboring 20,270 candidate SNPs were located on
      the M. truncatula (MT 3.5.1) chromosomes. Gene Ontology assignments indicate that
      sequences obtained cover a broad range of GO categories. CONCLUSIONS: We describe
      an efficient method to identify thousands of SNPs distributed throughout the
      alfalfa genome covering a broad range of GO categories. Validated SNPs represent
      valuable molecular marker resources that can be used to enhance marker density in
      linkage maps, identify potential factors involved in heterosis and genetic
      variation, and as tools for association mapping and genomic selection in alfalfa.

PMID- 21733172
TI  - 4D Flexible Atom-Pairs: An efficient probabilistic conformational space
      comparison for ligand-based virtual screening.
AB  - BACKGROUND: The performance of 3D-based virtual screening similarity functions is
      affected by the applied conformations of compounds. Therefore, the results of 3D
      approaches are often less robust than 2D approaches. The application of 3D
      methods on multiple conformer data sets normally reduces this weakness, but
      entails a significant computational overhead. Therefore, we developed a special
      conformational space encoding by means of Gaussian mixture models and a
      similarity function that operates on these models. The application of a model
      based encoding allows an efficient comparison of the conformational space of
      compounds. RESULTS: Comparisons of our 4D flexible atom-pair approach with over
      15 state-of-the-art 2D- and 3D-based virtual screening similarity functions on
      the 40 data sets of the Directory of Useful Decoys show a robust performance of
      our approach. Even 3D-based approaches that operate on multiple conformers yield
      inferior results. The 4D flexible atom-pair method achieves an averaged AUC value
      of 0.78 on the filtered Directory of Useful Decoys data sets. The best 2D- and 3D
      based approaches of this study yield an AUC value of 0.74 and 0.72, respectively.
      As a result, the 4D flexible atom-pair approach achieves an average rank of 1.25
      with respect to 15 other state-of-the-art similarity functions and four different
      evaluation metrics. CONCLUSIONS: Our 4D method yields a robust performance on 40
      pharmaceutically relevant targets. The conformational space encoding enables an
      efficient comparison of the conformational space. Therefore, the weakness of the
      3D-based approaches on single conformations is circumvented. With over 100,000
      similarity calculations on a single desktop CPU, the utilization of the 4D
      flexible atom-pair in real-world applications is feasible.

PMID- 21733173
TI  - Predictors for reproductive isolation in a ring species complex following genetic
      and ecological divergence.
AB  - BACKGROUND: Reproductive isolation (RI) is widely accepted as an important "check
      point" in the diversification process, since it defines irreversible evolutionary
      trajectories. Much less consensus exists about the processes that might drive RI.
      Here, we employ a formal quantitative analysis of genetic interactions at several
      stages of divergence within the ring species complex Ensatina eschscholtzii in
      order to assess the relative contribution of genetic and ecological divergence
      for the development of RI. RESULTS: By augmenting previous genetic datasets and
      adding new ecological data, we quantify levels of genetic and ecological
      divergence between populations and test how they correlate with a restriction of
      genetic admixture upon secondary contact. Our results indicate that the isolated
      effect of ecological divergence between parental populations does not result in
      reproductively isolated taxa, even when genetic transitions between parental taxa
      are narrow. Instead, processes associated with overall genetic divergence are the
      best predictors of reproductive isolation, and when parental taxa diverge in
      nuclear markers we observe a complete cessation of hybridization, even to
      sympatric occurrence of distinct evolutionary lineages. Although every parental
      population has diverged in mitochondrial DNA, its degree of divergence does not
      predict the extent of RI. CONCLUSIONS: These results show that in Ensatina, the
      evolutionary outcomes of ecological divergence differ from those of genetic
      divergence. While evident properties of taxa may emerge via ecological
      divergence, such as adaptation to local environment, RI is likely to be a
      byproduct of processes that contribute to overall genetic divergence, such as
      time in geographic isolation, rather than being a direct outcome of local
      adaptation.

PMID- 21733174
TI  - Single-step processing of copper-doped titania nanomaterials in a flame aerosol
      reactor.
AB  - Synthesis and characterization of long wavelength visible-light absorption Cu
      doped TiO2 nanomaterials with well-controlled properties such as size,
      composition, morphology, and crystal phase have been demonstrated in a single
      step flame aerosol reactor. This has been feasible by a detailed understanding of
      the formation and growth of nanoparticles in the high-temperature flame region.
      The important process parameters controlled were: molar feed ratios of
      precursors, temperature, and residence time in the high-temperature flame region.
      The ability to vary the crystal phase of the doped nanomaterials while keeping
      the primary particle size constant has been demonstrated. Results indicate that
      increasing the copper dopant concentration promotes an anatase to rutile phase
      transformation, decreased crystalline nature and primary particle size, and
      better suspension stability. Annealing the Cu-doped TiO2 nanoparticles increased
      the crystalline nature and changed the morphology from spherical to hexagonal
      structure. Measurements indicate a band gap narrowing by 0.8 eV (2.51 eV) was
      achieved at 15-wt.% copper dopant concentration compared to pristine TiO2 (3.31
      eV) synthesized under the same flame conditions. The change in the crystal phase,
      size, and band gap is attributed to replacement of titanium atoms by copper atoms
      in the TiO2 crystal.

PMID- 21733175
TI  - Microglial p38alpha MAPK is a key regulator of proinflammatory cytokine up
      regulation induced by toll-like receptor (TLR) ligands or beta-amyloid (Abeta).
AB  - BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia
      has been implicated as an important contributor to pathophysiology progression in
      both acute and chronic neurodegenerative diseases. Therefore, it is critical to
      elucidate intracellular signaling pathways that are significant contributors to
      cytokine overproduction in microglia exposed to specific stressors, especially
      pathways amenable to drug interventions. The serine/threonine protein kinase
      p38alpha MAPK is a key enzyme in the parallel and convergent intracellular
      signaling pathways involved in stressor-induced production of IL-1beta and
      TNFalpha in peripheral tissues, and is a drug development target for peripheral
      inflammatory diseases. However, much less is known about the quantitative
      importance of microglial p38alpha MAPK in stressor-induced cytokine
      overproduction, or the potential of microglial p38alpha MAPK to be a druggable
      target for CNS disorders. Therefore, we examined the contribution of microglial
      p38alphaMAPK to cytokine up-regulation, with a focus on the potential to suppress
      the cytokine increase by inhibition of the kinase with pharmacological or genetic
      approaches. METHODS: The microglial cytokine response to TLR ligands 2/3/4/7/8/9
      or to Abeta1-42 was tested in the presence of a CNS-penetrant p38alpha MAPK
      inhibitor, MW01-2-069A-SRM. Primary microglia from mice genetically deficient in
      p38alpha MAPK were used to further establish a linkage between microglia p38alpha
      MAPK and cytokine overproduction. The in vivo significance was determined by
      p38alpha MAPK inhibitor treatment in a LPS-induced model of acute
      neuroinflammation. RESULTS: Increased IL-1beta and TNFalpha production by the BV
      2 microglial cell line and by primary microglia cultures was inhibited in a
      concentration-dependent manner by the p38alpha MAPK-targeted inhibitor. Cellular
      target engagement was demonstrated by the accompanying decrease in the
      phosphorylation state of two p38alpha MAPK protein substrates, MK2 and MSK1.
      Consistent with the pharmacological findings, microglia from p38alpha-deficient
      mice showed a diminished cytokine response to LPS. Further, oral administration
      of the inhibitor blocked the increase of IL-1beta in the cerebral cortex of mice
      stressed by intraperitoneal injection of LPS. CONCLUSION: The p38alpha MAPK
      pathway is an important contributor to the increased microglial production of
      proinflammatory cytokines induced by diverse stressors. The results also indicate
      the feasibility of targeting p38alpha MAPK to modulate CNS proinflammatory
      cytokine overproduction.

PMID- 21733176
TI  - Anti-spasmodic action of crude methanolic extract and a new compound isolated
      from the aerial parts of Myrsine africana.
AB  - BACKGROUND: Myrsine africana is an herbaceous plant that is traditionally used as
      appetizer and carminative. Locally, it is used for the treatment of pulmonary
      tuberculosis, rheumatism and diarrhea by healers. The aims of the current study
      were to screen the crude methanol extract obtained from the aerial parts (leaves
      and stem) of M. africana, for antispasmodic actions on isolated tissues and
      further to subject the ethyl acetate (EtOAc) fraction of plant to column
      chromatography for isolation of pure compounds. METHODS: The antispasmodic action
      of the crude methanol extract was measured on the spontaneous rabbit's jejunum
      preparations at concentration 0.01, 0.03, 0.1, 0.3, 1.0, 5.0 and 10.0 mg/ml. The
      crude extract was also applied, in similar concentrations, on KCl (80 mM) induced
      contractions to explain its possible mode of action. RESULTS: A new compound
      Myrsigenin was isolated from the EtOAc fraction of M. africana. The structure of
      the compound was identified with the help of 13C-NMR, 1H-NMR, HMBC, HMQC, NOESY
      and COSY. The plant crude methanol extract showed a significant antispasmodic
      action on rabbit jejunum and abolished the tissue contraction completely at
      concentration of 5.0 mg/ml. CONCLUSION: The study concludes that the methanol
      crude extract of aerial parts of M. africana has antispasmodic action possibly
      through the calcium channel blocking mechanisms. A new compound Myrsigenin was
      isolated from the EtOAc fraction of the plant.

PMID- 21733177
TI  - Effect of a low fat versus a low carbohydrate weight loss dietary intervention on
      biomarkers of long term survival in breast cancer patients ('CHOICE'): study
      protocol.
AB  - BACKGROUND: Weight loss in overweight or obese breast cancer patients is
      associated with an improved prognosis for long term survival. However, it is not
      clear whether the macronutrient composition of the chosen weight loss dietary
      plan imparts further prognostic benefit. A study protocol is presented for a
      dietary intervention to investigate the effects of weight loss dietary patterns
      that vary markedly in fat and carbohydrate contents on biomarkers of exposure to
      metabolic processes that may promote tumorigenesis and that are predictive of
      long term survival. The study will also determine how much weight must be lost
      for biomarkers to change in a favorable direction. METHODS/DESIGN: Approximately
      370 overweight or obese postmenopausal breast cancer survivors (body mass index:
      25.0 to 34.9 kg/m2) will be accrued and assigned to one of two weight loss
      intervention programs or a non-intervention control group. The dietary
      intervention is implemented in a free living population to test the two extremes
      of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus
      a low carbohydrate, high fat diet. The effects of these dietary patterns on
      biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and
      steroid sex hormone metabolism will be measured. Participants will attend 3
      screening and dietary education visits, and 7 monthly one-on-one dietary
      counseling and clinical data measurement visits in addition to 5 group visits in
      the intervention arms. Participants in the control arm will attend two clinical
      data measurement visits at baseline and 6 months. The primary outcome is high
      sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor
      necrosis factor-alpha, insulin-like growth factor-1 (IGF), IGF binding protein-3,
      8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding
      globulin, adiponectin, and leptin. DISCUSSION: While clinical data indicate that
      excess weight for height is associated with poor prognosis for long term
      survival, little attention is paid to weight control in the clinical management
      of breast cancer. This study will provide information that can be used to answer
      important patient questions about the effects of dietary pattern and magnitude of
      weight loss on long term survival following breast cancer treatment. CLINICAL
      TRIAL REGISTRATION: CA125243.

PMID- 21733178
TI  - Early postoperative cognitive dysfunction and postoperative delirium after
      anaesthesia with various hypnotics: study protocol for a randomised controlled
      trial--the PINOCCHIO trial.
AB  - BACKGROUND: Postoperative delirium can result in increased postoperative
      morbidity and mortality, major demand for postoperative care and higher hospital
      costs. Hypnotics serve to induce and maintain anaesthesia and to abolish
      patients' consciousness. Their persisting clinical action can delay postoperative
      cognitive recovery and favour postoperative delirium. Some evidence suggests that
      these unwanted effects vary according to each hypnotic's specific pharmacodynamic
      and pharmacokinetic characteristics and its interaction with the individual
      patient.We designed this study to evaluate postoperative delirium rate after
      general anaesthesia with various hypnotics in patients undergoing surgical
      procedures other than cardiac or brain surgery. We also aimed to test whether
      delayed postoperative cognitive recovery increases the risk of postoperative
      delirium. METHODS/DESIGN: After local ethics committee approval, enrolled
      patients will be randomly assigned to one of three treatment groups. In all
      patients anaesthesia will be induced with propofol and fentanyl, and maintained
      with the anaesthetics desflurane, or sevoflurane, or propofol and the analgesic
      opioid fentanyl.The onset of postoperative delirium will be monitored with the
      Nursing Delirium Scale every three hours up to 72 hours post anaesthesia.
      Cognitive function will be evaluated with two cognitive test batteries (the Short
      Memory Orientation Memory Concentration Test and the Rancho Los Amigos Scale)
      preoperatively, at baseline, and postoperatively at 20, 40 and 60 min after
      extubation.Statistical analysis will investigate differences in the hypnotics
      used to maintain anaesthesia and the odds ratios for postoperative delirium, the
      relation of early postoperative cognitive recovery and postoperative delirium
      rate. A subgroup analysis will be used to categorize patients according to
      demographic variables relevant to the risk of postoperative delirium (age, sex,
      body weight) and to the preoperative score index for delirium. DISCUSSION: The
      results of this comparative anaesthesiological trial should whether each the
      three hypnotics tested is related to a significantly different postoperative
      delirium rate. This information could ultimately allow us to select the most
      appropriate hypnotic to maintain anaesthesia for specific subgroups of patients
      and especially for those at high risk of postoperative delirium. REGISTERED AT
      TRIAL.GOV NUMBER: ClinicalTrials.gov: NCT00507195.

PMID- 21733179
TI  - Ectopic cervical thymoma in a patient with myasthenia gravis.
AB  - Ectopic cervical thymoma is rare and is often misdiagnosed as a thyroid tumor or
      other malignancy. Ectopic thymic tissue can be found along the entire thymic
      descent path during embryogenesis. However, a thymoma arising from such ectopic
      thymic tissue is extremely rare. Herein we report a patient with ectopic cervical
      thymoma and myasthenia gravis (MG) and discuss the management.

PMID- 21733180
TI  - A web server for predicting inhibitors against bacterial target GlmU protein.
AB  - BACKGROUND: The emergence of drug resistant tuberculosis poses a serious concern
      globally and researchers are in rigorous search for new drugs to fight against
      these dreadful bacteria. Recently, the bacterial GlmU protein, involved in
      peptidoglycan, lipopolysaccharide and techoic acid synthesis, has been identified
      as an important drug target. A unique C-terminal disordered tail, essential for
      survival and the absence of gene in host makes GlmU a suitable target for
      inhibitor design. RESULTS: This study describes the models developed for
      predicting inhibitory activity (IC50) of chemical compounds against GlmU protein
      using QSAR and docking techniques. These models were trained on 84 diverse
      compounds (GlmU inhibitors) taken from PubChem BioAssay (AID 1376). These
      inhibitors were docked in the active site of the C-terminal domain of GlmU
      protein (2OI6) using the AutoDock. A QSAR model was developed using docking
      energies as descriptors and achieved maximum correlation of 0.35/0.12 (r/r2)
      between actual and predicted pIC50. Secondly, QSAR models were developed using
      molecular descriptors calculated using various software packages and achieved
      maximum correlation of 0.77/0.60 (r/r2). Finally, hybrid models were developed
      using various types of descriptors and achieved high correlation of 0.83/0.70
      (r/r2) between predicted and actual pIC50. It was observed that some molecular
      descriptors used in this study had high correlation with pIC50. We screened
      chemical libraries using models developed in this study and predicted 40
      potential GlmU inhibitors. These inhibitors could be used to develop drugs
      against Mycobacterium tuberculosis. CONCLUSION: These results demonstrate that
      docking energies can be used as descriptors for developing QSAR models. The
      current work suggests that docking energies based descriptors could be used along
      with commonly used molecular descriptors for predicting inhibitory activity
      (IC50) of molecules against GlmU. Based on this study an open source platform,
      http://crdd.osdd.net/raghava/gdoq, has been developed for predicting inhibitors
      GlmU.

PMID- 21733181
TI  - Effects of transplantation with bone marrow-derived mesenchymal stem cells
      modified by Survivin on experimental stroke in rats.
AB  - BACKGROUND: This study was performed to determine whether injury induced by
      cerebral ischemia could be further improved by transplantation with bone marrow
      derived mesenchymal stem cells (MSCs) modified by Survivin (SVV). METHODS: MSCs
      derived from bone marrow of male Sprague-Dawley rats were infected by the self
      inactive lentiviral vector GCFU carrying green fluorescent protein (GFP) gene and
      SVV recombinant vector (GCFU-SVV). In vitro, vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) were detected in infected MSCs
      supernatants under hypoxic conditions by ELSIA. In vivo, experiments consisted of
      three groups, one receiving intravenous injection of 500 MUl of phosphate
      buffered saline (PBS) without cells (control group) and two groups administered
      the same volume solution with either three million GFP-MSCs (group GFP) or
      SVV/GFP-MSCs (group SVV). All animals were submitted to 2-hour middle cerebral
      artery occlusion (MCAO) and then reperfusion. Differentiation and survival of the
      transplanted MSCs were determined by confocal microscope. Western blot was used
      to detect the expression of VEGF and bFGF in ischemic tissue. A 2,3,5
      triphenyltetrazolium chloride (TTC) staining was used to assess the infarct
      volume. Evaluation of neurological function was performed using a modified
      Neurological Severity Score (mNSS). RESULTS: In vitro, modification with SVV
      further increased secretion of VEGF and bFGF under hypoxic condition. In vivo,
      only very few transplantated cells co-expressed GFP and NeuN. The survival
      transplanted cells in the group SVV was 1.3-fold at 4 days after transplantation
      and 3.4-fold higher at 14 days after transplantation, respectively, when compared
      with group GFP. Expression of VEGF and bFGF in the ischemic tissue were further
      up-regulated by modification with SVV. Moreover, modification with SVV further
      reduced the cerebral infarct volume by 5.2% at 4 days after stroke and improved
      post-stroke neurological function at 14 days after transplantation. CONCLUSION:
      Modification with SVV could further enhance the therapeutic effects of MSCs
      possibly through improving the MSCs survival capacity and up-regulating the
      expression of protective cytokines in the ischemic tissue.

PMID- 21733182
TI  - Exercise training improves sleep pattern and metabolic profile in elderly people
      in a time-dependent manner.
AB  - Aging and physical inactivity are two factors that favors the development of
      cardiovascular disease, metabolic syndrome, obesity, diabetes, and sleep
      dysfunction. In contrast, the adoption a habitual of moderate exercise may
      present a non-pharmacological treatment alternative for sleep and metabolic
      disorders. We aimed to assess the effects of moderate exercise training on sleep
      quality and on the metabolic profile of elderly people with a sedentary
      lifestyle. Fourteen male sedentary, healthy, elderly volunteers performed
      moderate training for 60 minutes/day, 3 days/week for 24 wk at a work rate
      equivalent to the ventilatory aerobic threshold. The environment was kept at a
      temperature of 23 +/- 2  degrees C, with an air humidity 60 +/- 5%. Blood and
      polysomnographs analysis were collected 3 times: at baseline (1 week before
      training began), 3 and 6 months (after 3 and 6 months of training). Training
      promoted increasing aerobic capacity (relative VO2, time and velocity to VO2max;
      p < 0.05), and reduced serum NEFA, and insulin concentrations as well as improved
      HOMA index (p < 0.05), and increased adiponectin levels (p < 0.05), after 3
      months of training when compared with baseline data. The sleep parameters, awake
      time and REM sleep latency were decreased after 6 months exercise training (p <
      0.05) in relation baseline values. Our results demonstrate that the moderate
      exercise training protocol improves the sleep profile in older people, but the
      metabolism adaptation does not persist. Suggesting that this population requires
      training strategy modifications as to ensure consistent alterations regarding
      metabolism.

PMID- 21733183
TI  - Primary prevention of cardiovascular diseases: a cost study in family practices.
AB  - BACKGROUND: Considering the scarcity of health care resources and the high costs
      associated with cardiovascular diseases, we investigated the spending on
      cardiovascular primary preventive activities and the prescribing behaviour of
      primary preventive cardiovascular medication (PPCM) in Dutch family practices
      (FPs). METHODS: A mixed methods design was used, which consisted of a
      questionnaire (n = 80 FPs), video recordings of hypertension- or cholesterol
      related general practitioner visits (n = 56), and the database of Netherlands
      Information Network of General Practice (n = 45 FPs; n = 157,137 patients). The
      questionnaire and video recordings were used to determine the average frequency
      and time spent on cardiovascular primary preventive activities per FP
      respectively. Taking into account the annual income and full time equivalents of
      general practitioners, health care assistants, and practice nurses as well as the
      practice costs, the total spending on cardiovascular primary preventive
      activities in Dutch FPs was calculated. The database of Netherlands Information
      Network of General Practice was used to determine the prescribing behaviour in
      Dutch FPs by conducting multilevel regression models and adjusting for patient
      and practice characteristics. RESULTS: Total expenditure on cardiovascular
      primary preventive activities in FPs in 2009 was ?38.8 million (?2.35 per
      capita), of which 47% was spent on blood pressure measurements, 26% on
      cardiovascular risk profiling, and 11% on lifestyle counselling. Fifteen percent
      (?11 per capita) of all cardiovascular medication prescribed in FPs was a PPCM.
      FPs differed greatly on prescription of PPCM (odds ratio of 3.1). CONCLUSIONS:
      Total costs of cardiovascular primary preventive activities in FPs such as blood
      pressure measurements and lifestyle counselling are relatively low compared to
      the costs of PPCM. There is considerable heterogeneity in prescribing behaviour
      of PPCM between FPs. Further research is needed to determine whether such large
      differences in prescription rates are justified. Striving for an optimal use of
      cardiovascular primary preventive activities might lead to similar health
      outcomes, but may achieve important cost savings.

PMID- 21733184
TI  - Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to
      detoxification pathway in colon cancer cells.
AB  - BACKGROUND: Resistance to chemotherapy remains one of the principle obstacles to
      the treatment of colon cancer. In order to identify the molecular mechanism of
      this resistance, we investigated the role of the steroid and xenobiotic receptor
      (SXR) in the induction of drug resistance. Indeed, this nuclear receptor plays an
      important role in response to xenobiotics through the upregulation of
      detoxification genes. Following drug treatments, SXR is activated and interacts
      with the retinoid X receptor (RXR) to induce expression of some genes involved in
      drug metabolism such as phase I enzyme (like CYP), phase II enzymes (like UGT)
      and transporters (e.g. MDR1). RESULTS: In this study, we have shown that
      endogenous SXR is activated in response to SN-38, the active metabolite of the
      anticancer drug irinotecan, in human colon cancer cell lines. We have found that
      endogenous SXR translocates into the nucleus and associates with RXR upon SN-38
      treatment. Using ChIP, we have demonstrated that endogenous SXR, following its
      activation, binds to the native promoter of the CYP3A4 gene to induce its
      expression. RNA interference experiments confirmed SXR involvement in CYP3A4
      overexpression and permitted us to identify CYP3A5 and MRP2 transporter as SXR
      target genes. As a consequence, cells overexpressing SXR were found to be less
      sensitive to irinotecan treatment. CONCLUSIONS: Altogether, these results suggest
      that the SXR pathway is involved in colon cancer irinotecan resistance in colon
      cancer cell line via the upregulation of select detoxification genes.

PMID- 21733185
TI  - Fracture surgery of the extremities with the intra-operative use of 3D-RX: a
      randomized multicenter trial (EF3X-trial).
AB  - BACKGROUND: Posttraumatic osteoarthritis can develop after an intra-articular
      extremity fracture, leading to pain and loss of function. According to
      international guidelines, anatomical reduction and fixation are the basis for an
      optimal functional result. In order to achieve this during fracture surgery, an
      optimal view on the position of the bone fragments and fixation material is a
      necessity. The currently used 2D-fluoroscopy does not provide sufficient insight,
      in particular in cases with complex anatomy or subtle injury, and even an 18-26%
      suboptimal fracture reduction is reported for the ankle and foot. More intra
      operative information is therefore needed.Recently the 3D-RX-system was
      developed, which provides conventional 2D-fluoroscopic images as well as a 3D
      reconstruction of bony structures. This modality provides more information, which
      consequently leads to extra corrections in 18-30% of the fracture operations.
      However, the effect of the extra corrections on the quality of the anatomical
      fracture reduction and fixation as well as on patient relevant outcomes has never
      been investigated.The objective of this study protocol is to investigate the
      effectiveness of the intra-operative use of the 3D-RX-system as compared to the
      conventional 2D-fluoroscopy in patients with traumatic intra-articular fractures
      of the wrist, ankle and calcaneus. The effectiveness will be assessed in two
      different areas: 1) the quality of fracture reduction and fixation, based on the
      current golden standard, Computed Tomography. 2) The patient-relevant outcomes
      like functional outcome range of motion and pain. In addition, the diagnostic
      accuracy of the 3D-RX-scan will be determined in a clinical setting and a cost
      effectiveness as well as a cost-utility analysis will be performed.
      METHODS/DESIGN: In this protocol for an international multicenter randomized
      clinical trial, adult patients (age > 17 years) with a traumatic intra-articular
      fracture of the wrist, ankle or calcaneus eligible for surgery will be subjected
      to additional intra-operative 3D-RX. In half of the patients the surgeon will be
      blinded to these results, in the other half the surgeon may use the 3D-RX results
      to further optimize fracture reduction. In both randomization groups a CT-scan
      will be performed postoperatively. Based on these CT-scans the quality of
      fracture reduction and fixation will be determined. During the follow-up visits
      after hospital discharge at 6 and 12 weeks and 1 year postoperatively the patient
      relevant outcomes will be determined by joint specific, health economic and
      quality of life questionnaires. In addition a follow up study will be performed
      to determine the patient relevant outcomes and prevalence of posttraumatic
      osteoarthritis at 2 and 5 years postoperatively. DISCUSSION: The results of the
      study will provide more information on the effectiveness of the intra-operative
      use of 3D-imaging during surgical treatment of intra-articular fractures of the
      wrist, ankle and calcaneus. A randomized design in which patients will be
      allocated to a treatment arm during surgery will be used because of its high
      methodological quality and the ability to detect incongruences in the reduction
      and/or fixation that occur intra-operatively in the blinded arm of the 3D-RX. An
      alternative, pragmatic design could be to randomize before the start of the
      surgery, then two surgical strategies would be compared. This resembles clinical
      practice better, but introduces more bias and does not allow the assessment of
      incongruences that would have been detected by 3D-RX in the blinded arm. TRIAL
      REGISTRATION: Dutch Trial Register NTR 1902.

PMID- 21733186
TI  - CREST--a large and diverse superfamily of putative transmembrane hydrolases.
AB  - BACKGROUND: A number of membrane-spanning proteins possess enzymatic activity and
      catalyze important reactions involving proteins, lipids or other substrates
      located within or near lipid bilayers. Alkaline ceramidases are seven
      transmembrane proteins that hydrolyze the amide bond in ceramide to form
      sphingosine. Recently, a group of putative transmembrane receptors called
      progestin and adipoQ receptors (PAQRs) were found to be distantly related to
      alkaline ceramidases, raising the possibility that they may also function as
      membrane enzymes. RESULTS: Using sensitive similarity search methods, we
      identified statistically significant sequence similarities among several
      transmembrane protein families including alkaline ceramidases and PAQRs. They
      were unified into a large and diverse superfamily of putative membrane-bound
      hydrolases called CREST (alkaline ceramidase, PAQR receptor, Per1, SID-1 and
      TMEM8). The CREST superfamily embraces a plethora of cellular functions and
      biochemical activities, including putative lipid-modifying enzymes such as
      ceramidases and the Per1 family of putative phospholipases involved in lipid
      remodeling of GPI-anchored proteins, putative hormone receptors, bacterial
      hemolysins, the TMEM8 family of putative tumor suppressors, and the SID-1 family
      of putative double-stranded RNA transporters involved in RNA interference.
      Extensive similarity searches and clustering analysis also revealed several
      groups of proteins with unknown function in the CREST superfamily. Members of the
      CREST superfamily share seven predicted core transmembrane segments with several
      conserved sequence motifs. CONCLUSIONS: Universal conservation of a set of
      histidine and aspartate residues across all groups in the CREST superfamily,
      coupled with independent discoveries of hydrolase activities in alkaline
      ceramidases and the Per1 family as well as results from previous mutational
      studies of Per1, suggests that the majority of CREST members are metal-dependent
      hydrolases. REVIEWERS: This article was reviewed by Kira S. Markarova, Igor B.
      Zhulin and Rob Knight.

PMID- 21733187
TI  - Estrogen receptor beta expression in prostate adenocarcinoma.
AB  - BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in men and the
      second leading cause of cancer death in men. Estrogen induction of cell
      proliferation is a crucial step in carcinogenesis of gynecologic target tissues,
      and there are many studies recently done, showing that prostate cancer growth is
      also influenced by estrogen. The characterization of estrogen receptor beta (ER
      b) brought new insight into the mechanisms underlying estrogen signalling. In the
      present study, we investigated the expression of estrogen receptor-b (ER-b) in
      human prostate cancer tissues. METHODS: We selected 52 paraffin-embedded blocks
      of prostate needle biopsies in a cross-sectional study to determine frequency and
      rate of ER-b expression in different grades of prostate adenocarcinoma according
      to Gleason grading system. Immunohistochemical staining of tissue sections by
      monoclonal anti ER-b antibody was performed using an Envision method visualising
      system. RESULTS: ER-b expression was seen in tumoral cells of prostatic carcinoma
      in all 29 cases with low and intermediate tumors (100%) and 19 of 23 cases with
      high grade tumor (83%). Mean rate of ER-b expression in low & intermediate grade
      cancers was 68.41% (SD = 25.63) whereas high grade cancers showed 49.48% rate of
      expression (SD = 28.79). CONCLUSIONS: ER-b expression is reduced in high grade
      prostate cancers compared to low & intermediate grade ones (P value 0.027).

PMID- 21733188
TI  - Tinnitus referral pathways within the National Health Service in England: a
      survey of their perceived effectiveness among audiology staff.
AB  - BACKGROUND: In the UK, audiology services deliver the majority of tinnitus
      patient care, but not all patients experience the same level of service. In 2009,
      the Department of Health released a Good Practice Guide to inform commissioners
      about key aspects of a quality tinnitus service in order to promote equity of
      tinnitus patient care in UK primary care, audiology, and in specialist multi
      disciplinary centres. The purpose of the present research was to evaluate
      utilisation and opinions on pathways for the referral of tinnitus patients to and
      from English Audiology Departments. METHODS: We surveyed all audiology staff
      engaged in providing tinnitus services across England. A 36-item questionnaire
      was mailed to 351 clinicians in all 163 National Health Service (NHS) Trusts
      identified as having a tinnitus service. 138 clinicians responded. The results
      presented here describe experiences and opinions of the current patient pathways
      to and from the audiology tinnitus service. RESULTS: The most common referral
      pathway was from general practice to a hospital-based Ear, Nose & Throat
      department and from there to a hospital-based audiology department (64%).
      Respondents considered the NHS tinnitus referral process to be generally
      effective (67%), but expressed needs for improving GP referral and patients'
      access to services. 'Open access' to the audiology clinic was rarely an option
      for patients (9%), nor was the opportunity to access specialist counselling
      provided by clinical psychology (35%). To decrease the number of inappropriate
      referrals, 40% of respondents called for greater awareness by referrers about the
      audiology tinnitus service. CONCLUSIONS: Respondents in the present survey were
      generally satisfied with the tinnitus referral system. However, they highlighted
      some potential targets for service improvement including 1] faster and more
      appropriate referral from GPs, to be achieved through education on tinnitus
      referral criteria, 2] improved access to psychological services through
      audiologist training, and 3] ongoing support from tinnitus support groups,
      national charities, or open access to the tinnitus clinic for existing patients.

PMID- 21733189
TI  - Bilateral ureteropelvic disruption following blunt abdominal trauma: case report.
AB  - BACKGROUND: Ureteral injury occurs in less than 1% of blunt abdominal trauma
      cases, partly because the ureters are relatively well protected in the
      retroperitoneum. Bilateral ureteral injury is extremely rare, with only 10
      previously reported cases. Diagnosis may be delayed if ureteric injury is not
      suspected, and delay of 36 hours or longer has been observed in more than 50% of
      patients with ureteric injury following abdominal trauma, leading to increased
      morbidity. CASE PRESENTATION: A 29-year-old man was involved in a highway motor
      vehicle collision and was ejected from the front passenger seat even though
      wearing a seatbelt. He was in a preshock state at the scene of the accident. An
      intravenous line and left thoracic drain were inserted, and he was transported to
      our hospital by helicopter. Whole-body, contrast-enhanced computed tomography
      (CT) scan showed left diaphragmatic disruption, splenic injury, and a grade I
      injury to the left kidney with a retroperitoneal haematoma. He underwent
      emergency laparotomy. The left diaphragmatic and splenic injuries were repaired.
      Although a retroperitoneal haematoma was observed, his renal injury was treated
      conservatively because the haematoma was not expanding. In the intensive care
      unit, the patient's haemodynamic state was stable, but there was no urinary
      output for 9 hours after surgery. Anuresis prompted a review of the abdominal x
      ray which had been performed after the contrast-enhanced CT. Leakage of contrast
      material from the ureteropelvic junctions was detected, and review of the repeat
      CT scan revealed contrast retention in the perirenal retroperitoneum bilaterally.
      He underwent cystoscopy and bilateral retrograde pyelography, which showed
      bilateral complete ureteral disruption, preventing placement of ureteral stents.
      Diagnostic laparotomy revealed complete disruption of the ureteropelvic junctions
      bilaterally. Double-J ureteral stents were placed bilaterally and ureteropelvic
      anastomoses were performed. The patient's postoperative progress was satisfactory
      and he was discharged on the 23rd day. CONCLUSION: Diagnosis of ureteral injury
      was delayed, although delayed phase contrast-enhanced CT and abdominal x-rays
      performed after CT revealed the diagnosis early. Prompt detection and early
      repair prevented permanent renal damage and the necessity for nephrectomy.

PMID- 21733190
TI  - Bacteriophage-encoded shiga toxin gene in atypical bacterial host.
AB  - BACKGROUND: Contamination from fecal bacteria in recreational waters is a major
      health concern since bacteria capable of causing human disease can be found in
      animal feces. The Dog Beach area of Ocean Beach in San Diego, California is a
      beach prone to closures due to high levels of fecal indicator bacteria (FIB). A
      potential source of these FIB could be the canine feces left behind by owners who
      do not clean up after their pets. We tested this hypothesis by screening the DNA
      isolated from canine feces for the bacteriophage-encoded stx gene normally found
      in the virulent strains of the fecal bacterium Escherichia coli. RESULTS: Twenty
      canine fecal samples were collected, processed for total and bacterial fraction
      DNA, and screened by PCR for the stx gene. The stx gene was detected in the total
      and bacterial fraction DNA of one fecal sample. Bacterial isolates were then
      cultivated from the stx-positive fecal sample. Eighty nine of these canine fecal
      bacterial isolates were screened by PCR for the stx gene. The stx gene was
      detected in five of these isolates. Sequencing and phylogenetic analyses of 16S
      rRNA gene PCR products from the canine fecal bacterial isolates indicated that
      they were Enterococcus and not E. coli. CONCLUSIONS: The bacteriophage-encoded
      stx gene was found in multiple species of bacteria cultivated from canine fecal
      samples gathered at the shoreline of the Dog Beach area of Ocean Beach in San
      Diego, California. The canine fecal bacteria carrying the stx gene were not the
      typical E. coli host and were instead identified through phylogenetic analyses as
      Enterococcus. This suggests a large degree of horizontal gene transfer of
      exotoxin genes in recreational waters.

PMID- 21733191
TI  - Anti-inflammatory function of arctiin by inhibiting COX-2 expression via NF
      kappaB pathways.
AB  - BACKGROUND: Arctiin, isolated from Forsythia suspensa has been reported to have
      anti-inflammatory, anti-oxidant, antibacterial, and antiviral effects in vitro.
      However, there has been a lack of studies regarding its effects on immunological
      activity. The aim of this study is to investigate the anti-inflammatory potential
      and possible mechanisms of arctiin in LPS-induced macrophages. METHODS: We
      investigated the mRNA and protein levels of proinflammatory cytokines through RT
      PCR and western blot analysis, followed by a FACS analysis for surface molecule
      changes. RESULTS: Arctiin dose dependently decreased the production of NO and
      proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, and PGE2, and it
      reduced the gene and protein levels as determined by RT-PCR and western blot
      analysis, respectively. The expression of co-stimulatory molecules such as B7-1
      and B7-2 were also inhibited by arctiin. Furthermore, the activation of the
      nuclear transcription factor, NF-kappaB in macrophages was inhibited by arctiin.
      CONCLUSION: Taken together these results provide evidence of the bioactivity of
      arctiin in inflammatory diseases and suggest that arctiin may exert anti
      inflammatory effect by inhibiting the pro-inflammatory mediators through the
      inactivation of NF-kB.

PMID- 21733192
TI  - Recombinant immunotoxin anti-c-Met/PE38KDEL inhibits proliferation and promotes
      apoptosis of gastric cancer cells.
AB  - BACKGROUND: Our study aims to evaluate the anti-growth effects of recombinant
      immunotoxin (IT) anti-c-Met/PE38KDEL on gastric cancer cells, and its mechnisms.
      METHODS: Gastric cancer cells were treated with increasing doses of IT and c-Met
      protein was quantified by Western blotting. Cell proliferation was determined by
      Cell Counting Kit-8 assay (CCK). [3H]-leucine incorporation assay was used to
      evaluate IT inhibition of protein synthesis. Cell apoptosis was quantified by
      flow cytometry. Caspase activities were measured using colorimetric protease
      assays. RESULTS: Cell growth and protein synthesis of the gastric cancer cell
      lines were suppressed by IT in a dose- and time-dependent manner. IT also induced
      apoptosis in a dose-dependent manner. The apoptosis rates of gastric cancer cell
      lines MKN-45 and SGC7901 were 19.19% and 27.37%, respectively when treated with
      50 ng/ml of IT. There were significant increase of caspase-3 activity at 24 hr of
      IT treatment (100 ng/ml) (P < 0.01) in these gastric cancer cell lines.
      CONCLUSIONS: IT anti-c-Met/PE38KDEL has anti-growth effects on the gastric cancer
      cell lines in vitro, and it provides an experimental basis for c-Met-targeted
      therapy towards in vivo testing.

PMID- 21733193
TI  - Endocarditis caused by methicillin-susceptible Staphylococcus aureus with reduced
      susceptibility to vancomycin: a case report.
AB  - INTRODUCTION: Staphylococcus aureus is the most common cause of acute infective
      endocarditis.Recent reports have described heteroresistance to vancomycin
      associated with methicillin-resistant Staphylococcus aureus. We present the first
      case report in Argentina of the failure of treatment with vancomycin in
      endocarditis caused by methicillin-susceptible Staphylococcus aureus containing
      subpopulations with reduced susceptibility to vancomycin. CASE PRESENTATION: We
      report the case of a 66-year-old Hispanic man with infective endocarditis
      complicated by septic emboli in the lumbosacral spine and the left iliopsoas
      muscle. This disease was caused by methicillin-susceptible Staphylococcus aureus
      containing subpopulations with reduced susceptibility to vancomycin. He was
      initially treated with cephalothin and gentamicin but developed a rash caused by
      beta-lactams and interstitial nephritis. For that reason, the treatment was
      subsequently switched to vancomycin but he failed to respond. The infection
      resolved after administration of vancomycin in combination with gentamicin and
      rifampin. CONCLUSION: Our case report provides important evidence for the
      existence of subpopulations of methicillin-susceptible Staphylococcus aureus that
      have reduced susceptibility to vancomycin which would account for treatment
      failure. Our case raises an alert about the existence of these strains and
      highlights the need to determine the vancomycin minimum inhibitory concentration
      of Staphylococcus aureus to screen for the presence of strains that have reduced
      vancomycin susceptibility at different infection sites.

PMID- 21733194
TI  - Occupational risk factors for Parkinson's disease: a case-control study in Japan.
AB  - BACKGROUND: The evidence for associations between occupational factors and the
      risk of Parkinson's disease (PD) is inconsistent. We assessed the risk of PD
      associated with various occupational factors in Japan. METHODS: We examined 249
      cases within 6 years of onset of PD. Control subjects were 369 inpatients and
      outpatients without neurodegenerative disease. Information on occupational
      factors was obtained from a self-administered questionnaire. Relative risks of PD
      were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) based
      on logistic regression. Adjustments were made for gender, age, region of
      residence, educational level, and pack-years of smoking. RESULTS: Working in a
      professional or technical occupation tended to be inversely related to the risk
      of PD: adjusted OR was 0.59 (95% CI: 0.32-1.06, P = 0.08). According to a
      stratified analysis by gender, the decreased risk of PD for persons in
      professional or technical occupations was statistically significant only for men.
      Adjusted ORs for a professional or technical occupation among men and women were
      0.22 (95% CI: 0.06-0.67) and 0.99 (0.47-2.07), respectively, and significant
      interaction was observed (P = 0.048 for homogeneity of OR). In contrast, risk
      estimates for protective service occupations and transport or communications were
      increased, although the results were not statistically significant: adjusted ORs
      were 2.73 (95% CI: 0.56-14.86) and 1.74 (95% CI: 0.65-4.74), respectively. No
      statistical significance was seen in data concerning exposure to occupational
      agents and the risk of PD, although roughly a 2-fold increase in OR was observed
      for workers exposed to stone or sand. CONCLUSION: The results of our study
      suggest that occupational factors do not play a substantial etiologic role in
      this population. However, among men, professional or technical occupations may
      decrease the risk of PD.

PMID- 21733195
TI  - Cause for concern in the use of non-steroidal anti-inflammatory medications in
      the community--a population-based study.
AB  - BACKGROUND: Non-steroidal anti-inflammatory (NSAID) medications are a common
      cause of reported adverse drug side-effects. This study describes the prevalence
      of non-steroidal anti-inflammatory (NSAID) use (other than low-dose aspirin) and
      the presence of co-existing relative contraindications to NSAID use and chronic
      conditions in a representative population sample. METHODS: Data were analysed
      from 3,206 adults attending first follow-up of the North West Adelaide Health
      Study (NWAHS) in 2004-2006, a longitudinal representative population study.
      Medications were brought into study clinic visits by participants. Clinical
      assessment included measured blood pressure, kidney function, serum cholesterol,
      blood glucose. Questionnaires assessed demographics, lifestyle risk factors,
      physician-diagnosed chronic conditions. Data were weighted to census measures by
      region, age group, gender, and probability of selection in the household, to
      provide population representative estimates. Pearson's Chi-square tests
      determined significant differences in proportions. Multiple logistic regression
      was used to examine associations of socio-demographic characteristics with use of
      NSAIDs. RESULTS: Of 3,175 participants, 357 (11.2%), and 16% of those aged > 55
      years, reported using either non-specific NSAIDs or COX-2 inhibitors, other than
      low-dose aspirin. Among people using NSAIDs, 60.8% had hypertension, 30.8% had
      Stage 3 or higher chronic kidney disease, 17.2% had a history of cardiovascular
      disease (CVD) and 20.7% had a > 15% 10-year CVD risk. The prevalence of NSAID use
      among people with hypertension was 16%, with kidney disease 15.9%, and a history
      of CVD 20.0%. Among people taking diuretics, 24.1% were also taking NSAIDs, and
      of those taking medications for gastro-esophageal reflux, 24.7% were on NSAIDs.
      Prescription-only COX-2 inhibitors, but not other NSAIDs, were used more by
      people > 75 years than by 35-54 year olds (OR 3.7, 95% CI 2.0, 6.7), and also
      were more commonly used by people with hypertension, cardiac and kidney disease.
      CONCLUSIONS: There is a high prevalence of current NSAID use among groups at-risk
      for significant drug-related adverse events or who have major chronic conditions
      that are relative contraindications to NSAID use. Assessment of absolute risks
      regarding cardiovascular and kidney disease need to take into account use of
      medications such as NSAIDs. The potential to make a substantial impact on chronic
      disease burden via improved use of NSAIDs is considerable.

PMID- 21733196
TI  - CGGBP1 regulates cell cycle in cancer cells.
AB  - BACKGROUND: CGGBP1 is a CGG-triplet repeat binding protein, which affects
      transcription from CGG-triplet-rich promoters such as the FMR1 gene and the
      ribosomal RNA gene clusters. Earlier, we reported some previously unknown
      functions of CGGBP1 in gene expression during heat shock stress response.
      Recently we had found CGGBP1 to be a cell cycle regulatory midbody protein
      required for normal cytokinetic abscission in normal human fibroblasts, which
      have all the cell cycle regulatory mechanisms intact. RESULTS: In this study we
      explored the role of CGGBP1 in the cell cycle in various cancer cell lines.
      CGGBP1 depletion by RNA interference in tumor-derived cells caused an increase in
      the cell population at G0/G1 phase and reduced the number of cells in the S
      phase. CGGBP1 depletion also increased the expression of cell cycle regulatory
      genes CDKN1A and GAS1, associated with reductions in histone H3 lysine 9
      trimethylation in their promoters. By combining RNA interference and genetic
      mutations, we found that the role of CGGBP1 in cell cycle involves multiple
      mechanisms, as single deficiencies of CDKN1A, GAS1 as well as TP53, INK4A or ARF
      failed to rescue the G0/G1 arrest caused by CGGBP1 depletion. CONCLUSIONS: Our
      results show that CGGBP1 expression is important for cell cycle progression
      through multiple parallel mechanisms including the regulation of CDKN1A and GAS1
      levels.

PMID- 21733197
TI  - Intimate partner violence towards women.
AB  - INTRODUCTION: Between 10% and 70% of women may have been physically or sexually
      assaulted by a partner at some stage, with assault rates against men reported at
      about one quarter of the rate against women. In at least half of people studied,
      the problem lasts for 5 years or more. Women reporting intimate partner violence
      (IPV) are more likely than other women to complain of poor physical or mental
      health, and of disability. METHODS AND OUTCOMES: We conducted a systematic review
      and aimed to answer the following clinical question: What are the effects of
      interventions initiated by healthcare professionals aimed at female victims of
      intimate partner violence? We searched: Medline, Embase, The Cochrane Library,
      and other relevant databases up to September 2009 (Clinical Evidence reviews are
      updated periodically, please check our website for the most up-to-date version of
      this review). RESULTS: We found 26 systematic reviews, RCTs, or observational
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review we
      present information relating to the effectiveness and safety of the following
      interventions: advocacy; career counselling plus critical consciousness
      awareness; cognitive behavioural counselling; cognitive trauma therapy;
      counselling; nurse support and guidance; peer support groups; safety planning;
      and shelters.

PMID- 21733198
TI  - Primary prevention of CVD: treating hypertension.
AB  - INTRODUCTION: Hypertension (persistent diastolic blood pressure of 90 mm Hg or
      greater and systolic blood pressure 140 mm Hg or greater) affects 20% of the
      world's adult population, and increases the risk of cardiovascular disease, end
      stage renal disease, and retinopathy. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of different antihypertensive drugs for people with hypertension?
      What are the effects of dietary modification for people with hypertension? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to December 2007 (Clinical Evidence reviews are updated periodically, please
      check our website for the most up-to-date version of this review). We included
      harms alerts from relevant organisations such as the US Food and Drug
      Administration (FDA) and the UK Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: We found 21 systematic reviews, RCTs, or observational
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review we
      present information relating to the effectiveness and safety of the following
      interventions: a low-salt diet, antihypertensive drugs, calcium supplements, fish
      oil supplements, magnesium supplements, and potassium supplements.

PMID- 21733199
TI  - Urinary tract infection in children.
AB  - INTRODUCTION: Up to 11.3% of girls and 3.6% of boys will have had a urinary tract
      infection (UTI) by the age of 16 years, and recurrence of infection is common.
      Vesicoureteric reflux is identified in up to 40% of children being investigated
      for a first UTI, and is a risk factor for, but weak predictor of, renal
      parenchymal defects. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical questions: What are the effects of
      treatment of acute urinary tract infection in children? What are the effects of
      interventions to prevent recurrence? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to July 2009 (Clinical Evidence reviews
      are updated periodically, please check our website for the most up-to-date
      version of this review). We included harms alerts from relevant organisations
      such as the US Food and Drug Administration (FDA) and the UK Medicines and
      Healthcare products Regulatory Agency (MHRA). RESULTS: We found 25 systematic
      reviews, RCTs, or observational studies that met our inclusion criteria. We
      performed a GRADE evaluation of the quality of evidence for interventions.
      CONCLUSIONS: In this systematic review we present information relating to the
      effectiveness and safety of the following interventions: antibiotics (short
      initial intravenous antibiotics, long initial intravenous antibiotics, initial
      oral antibiotics, single-dose or single-day courses of oral antibiotics, short
      courses of oral antibiotics, long courses of oral antibiotics, immediate
      empirical antibiotics, delayed antibiotics, prolonged delay of antibiotics,
      prophylactic antibiotics); immunotherapy; surgical correction of minor functional
      abnormalities; and surgical correction of moderate to severe vesicoureteric
      reflux.

PMID- 21733200
TI  - Partner notification.
AB  - INTRODUCTION: Many people diagnosed with a sexually transmitted disease (STD) do
      not have symptoms, and may not inform their past or current sexual partners of
      their diagnosis or routinely use condoms. Several strategies have been used to
      notify and treat partners of people diagnosed with an STD, but only a limited
      number of RCTs of their effectiveness have been undertaken. METHODS AND OUTCOMES:
      We conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of partner notification strategies in people with
      different STDs? What are the effects of interventions to improve effectiveness of
      patient referral in people with STDs? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to August 2008 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 17
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions: contract
      referral; counselling (both alone and in combination with educational
      interventions) of index patients; educational interventions for the index
      patient; information for the index patient or partner; outreach assistance;
      patient referral; patient referral via different types of healthcare
      professional; patient-delivered partner therapy; patient-delivered home-sampling
      kits; provider referral; and reminders (any format) for the index patient.

PMID- 21733201
TI  - Multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis is the most common cause of neurological
      disability in young adults. Irreversible disability can occur, but life
      expectancy is generally not affected. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of interventions aimed at reducing relapse rates and disability in
      people with multiple sclerosis? What are the effects of interventions to improve
      symptoms during acute relapse? What are the effects of treatments for fatigue,
      spasticity, and multidisciplinary care on disability in people with multiple
      sclerosis? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to June 2008 (Clinical Evidence reviews are updated
      periodically, please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 68 systematic reviews, RCTs, and
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following key interventions: amantadine, azathioprine, behaviour
      modification, botulinum toxin, corticosteroids, exercise, gabapentin, inpatient
      or outpatient rehabilitation, interferon beta, intrathecal baclofen, intravenous
      immunoglobulin, methotrexate, mitoxantrone, modafinil, natalizumab, oral drug
      treatments, parenteral glatiramer acetate, physiotherapy, and plasma exchange.

PMID- 21733202
TI  - NSAIDs.
AB  - INTRODUCTION: NSAIDs are widely used. Almost 10% of people in The Netherlands
      used a non-aspirin NSAID in 1987, and the overall use was 11 defined daily doses
      per 1000 population a day. In Australia in 1994, overall use was 35 defined daily
      doses per 1000 population a day, with 36% of the people receiving NSAIDs for
      osteoarthritis, 42% for sprain and strain or low back pain, and 4% for rheumatoid
      arthritis; 35% of the people receiving NSAIDs were aged over 60 years. METHODS
      AND OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: Are there any important differences between oral NSAIDs? What
      are the effects of topical NSAIDs; and of co-treatments to reduce the risk of
      gastrointestinal adverse effects of oral NSAIDs? We searched: Medline, Embase,
      The Cochrane Library, and other important databases up to September 2009
      (Clinical Evidence reviews are updated periodically, please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      36 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the benefits and harms of the following interventions: differences in
      efficacy among different oral NSAIDs, between oral and topical NSAIDs, and
      between oral NSAIDs and alternative analgesics; dose-response relationship of
      oral NSAIDs; and H(2) blockers, misoprostol, or proton pump inhibitors to
      mitigate gastrointestinal adverse effects of oral NSAIDs.

PMID- 21733203
TI  - Squamous cell carcinoma of the skin (non-metastatic).
AB  - INTRODUCTION: Cutaneous squamous cell carcinoma is a malignant tumour of
      keratinocytes arising in the epidermis, with histological evidence of dermal
      invasion. Incidence varies by country and skin colour, and is as high as
      400/100,000 in Australia. People with fair skin colour who sunburn easily without
      tanning, people with xeroderma pigmentosum, and people who are immunosuppressed
      are most susceptible to squamous cell carcinoma. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: Does the use of sunscreen help prevent cutaneous squamous cell
      carcinoma and solar keratosis? What is the optimal margin for primary excision of
      cutaneous squamous cell carcinoma (non-metastatic)? Does micrographically
      controlled surgery result in lower rates of local recurrence than standard
      primary excision in people with squamous cell carcinoma of the skin (non
      metastatic)? Does radiotherapy after surgery affect local recurrence of cutaneous
      squamous cell carcinoma in people with squamous cell carcinoma of the skin (non
      metastatic)? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to October 2009 (Clinical Evidence reviews are updated
      periodically, please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 11 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: micrographically controlled surgery, primary
      excision, radiotherapy after surgery, and sunscreens.

PMID- 21733204
TI  - Follow-up of tetralogy of Fallot patients: tertiary centre versus satellite
      clinic.
AB  - BACKGROUND: Canadian Cardiovascular Society consensus guidelines recommend that
      tetralogy of Fallot patients be seen by a congenital cardiologist every 2 years.
      In Atlantic Canada, tetralogy of Fallot patients are followed up at either
      tertiary or satellite clinics, which are held in the community and attended by
      paediatric cardiologists. The effectiveness of satellite clinics in congenital
      cardiac disease follow-up is unproven. Our objective was to compare patient
      reported quality of life measures to determine whether these were impacted by the
      site of follow-up. METHODS: We included patients with tetralogy of Fallot
      undergoing surgical repair at the Izaak Walton Killam Health Centre from 1
      November, 1972 to 31 May, 2002. Quality of life surveys, SF-10 or SF-36v2, were
      administered to consenting patients. We analysed the subjective health status by
      patient age and site of follow-up. RESULTS: Of the 184 eligible patients, 72 were
      lost to follow-up. Of the locatable patients, 61% completed the questionnaires.
      In all, 90% (101 out of 112) were followed up at recommended intervals. Of the
      112 (68%) patients, 76 were followed up at a tertiary clinic. These patients were
      older, with a mean age of 18.4 years versus 14.7 years, and scored higher on the
      SF-36 physical component summary (52.6 versus 45.7, p = 0.02) compared with
      satellite clinic patients. The SF-36 mental component summary scores were similar
      for patients regardless of the site of follow-up. SF-10 physical and psychosocial
      scores were similar regardless of the site of follow-up. CONCLUSION: Tetralogy of
      Fallot patients followed at either satellite or tertiary clinics have similar
      subjective health status.

PMID- 21733205
TI  - Age-dependent effects of milrinone and levosimendan on ventricular function and
      haemodynamics in newborn and mature pigs.
AB  - Inodilators are used in the treatment of low cardiac output, mainly after cardiac
      surgery. At present, there is little knowledge of the effect of inodilators in
      the newborn heart. Immediately after birth and in the neonatal period, the
      metabolism and physiology of the heart undergo major changes. We hypothesised
      that effects of the inodilators milrinone and levosimendan on myocardial
      contractility and haemodynamics under normal physiological conditions were age
      dependent. Animal studies were conducted on 48 pigs using a closed-chest
      biventricular conductance catheter method. Pigs in two age groups, that is, 5-6
      days and 5-6 weeks, were assigned to milrinone, levosimendan, or a control group.
      We observed that both milrinone - 19.2% with a p value of 0.05 - and levosimendan
      - 25.7% with a p value of 0.03 compared with the control group increased cardiac
      output, as well as myocardial contractility with a maximum pressure development
      over time: milrinone 28.2%, p = 0.01 and levosimendan 19.4%, p = 0.05. Milrinone
      improved diastolic performance (p < 0.05) in the left ventricle in the 5-6-week
      old animals. In the newborn animals, neither of the inodilators increased
      ventricular contractility or cardiac output; however, we observed a significant
      decrease in the mean arterial pressure: milrinone 34.6%, p < 0.01 and
      levosimendan 30.1%, p = 0.02. Both inodilators demonstrated age-dependent
      haemodynamic effects, and it is noteworthy that neither milrinone nor
      levosimendan was able to increase cardiac output in the newborn heart.

PMID- 21733206
TI  - Cardiac computed tomography and conventional angiography in the diagnosis of
      congenital cardiac disease in children: recent trends and radiation doses.
AB  - BACKGROUND: The use of imaging that employs ionising radiation is increasing in
      the setting of paediatric cardiology. Children's high radiosensitivity and the
      lack of contemporary radiation data warrant a review of the radiation doses from
      the latest "state-of-the-art" angiography and computed tomography systems.
      OBJECTIVES: In children aged less than 16 years with congenital cardiac disease,
      we aimed to report: recent trends in the use of diagnostic angiography and
      cardiac dual-source computed tomography; the characteristics, lesions, and
      imaging histories of patients undergoing these procedures; and the average
      radiation doses imparted by each modality. STUDY DESIGN: Retrospective review of
      consecutive cases undergoing cardiac computed tomography or diagnostic
      angiography in a teaching hospital between January, 2008 and December, 2009.
      Radiation doses were converted to effective doses (millisievert) using published
      conversion factors. RESULTS: Angiography was performed 3.7 times more often than
      computed tomography. Computed tomography examinations increased by 92.5%, whereas
      angiography decreased by 26.4% in 2009 compared with 2008. Patients undergoing
      computed tomography were younger and weighed less than those undergoing
      angiography, but lesions were similar between the 2 groups. Multiple lifetime
      angiography was more prevalent than multiple lifetime computed tomography (p <
      0.001). The median procedural dose - range - from angiography and computed
      tomography was 5 (0.2-27.8) and 1.7 (0.5-9.5) millisieverts, respectively (p <
      0.001). CONCLUSION: Despite not being completely analogous investigations,
      computed tomography should be considered prior to angiography and not withheld on
      radiation dose concerns, given that it imparts lower and more consistent doses
      than conventional angiography.

PMID- 21733207
TI  - Impulsivity and cognitive distortions in pathological gamblers attending the UK
      National Problem Gambling Clinic: a preliminary report.
AB  - BACKGROUND: Pathological gambling (PG) is a form of behavioural addiction that
      has been associated with elevated impulsivity and also cognitive distortions in
      the processing of chance, probability and skill. We sought to assess the
      relationship between the level of cognitive distortions and state and trait
      measures of impulsivity in treatment-seeking pathological gamblers. METHOD:
      Thirty pathological gamblers attending the National Problem Gambling Clinic, the
      first National Health Service clinic for gambling problems in the UK, were
      compared with 30 healthy controls in a case-control design. Cognitive distortions
      were assessed using the Gambling-Related Cognitions Scale (GRCS). Trait
      impulsivity was assessed using the UPPS-P, which includes scales of urgency, the
      tendency to be impulsive in positive or negative mood states. Delay discounting
      rates were taken as a state measure of impulsive choice. RESULTS: Pathological
      gamblers had elevated impulsivity on several UPPS-P subscales but effect sizes
      were largest (Cohen's d>1.4) for positive and negative urgency. The pathological
      gamblers also displayed higher levels of gambling distortions, and elevated
      preference for immediate rewards, compared to controls. Within the pathological
      gamblers, there was a strong relationship between the preference for immediate
      rewards and the level of cognitive distortions (R2=0.41). CONCLUSIONS: Impulsive
      choice in the gamblers was correlated with the level of gambling distortions, and
      we hypothesize that an impulsive decision-making style may increase the
      acceptance of erroneous beliefs during gambling play.

PMID- 21733208
TI  - Perceptual processing advantages for trauma-related visual cues in post-traumatic
      stress disorder.
AB  - BACKGROUND: Intrusive re-experiencing in post-traumatic stress disorder (PTSD)
      comprises distressing sensory impressions from the trauma that seem to occur 'out
      of the blue'. A key question is how intrusions are triggered. One possibility is
      that PTSD is characterized by a processing advantage for stimuli that resemble
      those that accompanied the trauma, which would lead to increased detection of
      such cues in the environment. METHOD: We used a blurred picture identification
      task in a cross-sectional (n=99) and a prospective study (n=221) of trauma
      survivors. RESULTS: Participants with acute stress disorder (ASD) or PTSD, but
      not trauma survivors without these disorders, identified trauma-related pictures,
      but not general threat pictures, better than neutral pictures. There were no
      group differences in the rate of trauma-related answers to other picture
      categories. The relative processing advantage for trauma-related pictures
      correlated with re-experiencing and dissociation, and predicted PTSD at follow
      up. CONCLUSIONS: A perceptual processing bias for trauma-related stimuli may
      contribute to the involuntary triggering of intrusive trauma memories in PTSD.

PMID- 21733209
TI  - Is childhood OCD a risk factor for eating disorders later in life? A longitudinal
      study.
AB  - BACKGROUND: It has been suggested that childhood obsessive-compulsive disorder
      (OCD) may be a risk factor for the development of an eating disorder (ED) later
      in life, but prospective studies are lacking. We aimed to determine the
      prevalence of ED at follow-up and clinical predictors in a longitudinal clinical
      sample of adolescents/young adults diagnosed with OCD in childhood. METHOD: All
      contactable (n=231) young people with OCD assessed over 9 years at a national and
      specialist paediatric OCD clinic were included in this study. At follow-up, 126
      (57%) young people and parents completed the ED section of the Developmental and
      Well-being Assessment. Predictors for ED were investigated using logistic
      regression. RESULTS: In total, 16 participants (12.7%) had a diagnosis of ED at
      follow-up. Having an ED was associated with female gender and persistent OCD at
      follow-up. There was a trend for family history of ED being predictive of ED
      diagnosis. Five (30%) of those who developed an ED at follow-up had ED symptoms
      or food-related obsessions/compulsions at baseline. A difference in predictors
      for an ED versus other anxiety disorders at follow-up was identified.
      CONCLUSIONS: This study provides initial evidence that baseline clinical
      predictors such as female gender and family history of ED might be specific to
      the later development of ED in the context of childhood OCD. Clinicians should be
      alert to ED subthreshold symptoms in young girls presenting with OCD. Future
      longitudinal studies are needed to clarify the relationship between childhood OCD
      and later ED.

PMID- 21733210
TI  - Visual memory as a potential cognitive endophenotype of attention deficit
      hyperactivity disorder.
AB  - BACKGROUND: Executive functions have been proposed as endophenotypes for
      attention deficit hyperactivity disorder (ADHD); however, data regarding visual
      memory are lacking. We therefore assessed visual memory in adolescents with ADHD
      and their unaffected siblings compared with controls. METHOD: The participants
      included 279 adolescents with ADHD, 108 unaffected siblings, and 173 unaffected
      school controls. They were assessed by using the visual memory tasks of the
      Cambridge Neuropsychological Test Automated Battery (CANTAB): Delayed Matching to
      Sample (DMS), Spatial Recognition Memory (SRM), Paired Associates Learning (PAL),
      and Pattern Recognition Memory (PRM). RESULTS: Compared with the controls,
      probands with ADHD had a significantly lower number of correct responses, a
      higher probability of an error following a correct response and following an
      error response in the DMS, and a lower percentage of correct responses in the
      SRM. Their unaffected siblings occupied an intermediate position between ADHD
      probands and controls in the probability of an error following a correct response
      and following an error response in the DMS, and in the percentage of correct
      responses in the SRM. In general, lower IQ and current use of and duration of
      treatment with methylphenidate were associated with more severe visual memory
      deficits. CONCLUSIONS: The present results suggest that ADHD is associated with
      poorer visual memory function. Visual memory assessed by the DMS and SRM tasks in
      the CANTAB may be a useful endophenotype for ADHD.

PMID- 21733211
TI  - The structure of mental health research: networks of influence among psychiatry
      and clinical psychology journals.
AB  - BACKGROUND: Psychiatry and clinical psychology are the two dominant disciplines
      in mental health research, but the structure of scientific influence and
      information flow within and between them has never been mapped. METHOD: Citations
      among 96 of the highest impact psychiatry and clinical psychology journals were
      examined, based on 10 052 articles published in 2008. Network analysis explored
      patterns of influence between journal clusters. RESULTS: Psychiatry journals
      tended to have greater influence than clinical psychology journals, and their
      influence was asymmetrical: clinical psychology journals cited psychiatry
      journals at a much higher rate than the reverse. Eight journal clusters were
      found, most dominated by a single discipline. Their citation network revealed an
      influential central cluster of 'core psychiatry' journals that had close
      affinities with a 'psychopharmacology' cluster. A group of 'core clinical
      psychology' journals was linked to a 'behavior therapy' cluster but both were
      subordinate to psychiatry journals. Clinical psychology journals were less
      integrated than psychiatry journals, and 'health psychology/behavioral medicine'
      and 'neuropsychology' clusters were relatively peripheral to the network.
      CONCLUSIONS: Scientific publication in the mental health field is largely
      organized along disciplinary lines, and is to some degree hierarchical, with
      clinical psychology journals tending to be structurally subordinate to psychiatry
      journals.

PMID- 21733212
TI  - Familial clustering of suicide risk: a total population study of 11.4 million
      individuals.
AB  - BACKGROUND: Research suggests that suicidal behaviour is aggregated in families.
      However, due to methodological limitations, including small sample sizes, the
      strength and pattern of this aggregation remains uncertain. METHOD: We examined
      the familial clustering of completed suicide in a Swedish total population
      sample. We linked the Cause of Death and Multi-Generation Registers and compared
      suicide rates among relatives of all 83 951 suicide decedents from 1952-2003 with
      those among relatives of population controls. RESULTS: Patterns of familial
      aggregation of suicide among relatives to suicide decedents suggested genetic
      influences on suicide risk; the risk among full siblings (odds ratio 3.1, 95%
      confidence interval 2.8-3.5, 50% genetic similarity) was higher than that for
      maternal half-siblings (1.7, 1.1-2.7, 25% genetic similarity), despite similar
      environmental exposure. Further, monozygotic twins (100% genetic similarity) had
      a higher risk than dizygotic twins (50% genetic similarity) and cousins (12.5%
      genetic similarity) had higher suicide risk than controls. Shared (familial)
      environmental influences were also indicated; siblings to suicide decedents had a
      higher risk than offspring (both 50% genetically identical but siblings having a
      more shared environment, 3.1, 2.8-3.5 v. 2.0, 1.9-2.2), and maternal half
      siblings had a higher risk than paternal half-siblings (both 50% genetically
      identical but the former with a more shared environment). Although comparisons of
      twins and half-siblings had overlapping confidence intervals, they were supported
      by sensitivity analyses, also including suicide attempts. CONCLUSIONS: Familial
      clustering of suicide is primarily influenced by genetic and also shared
      environmental factors. The family history of suicide should be considered when
      assessing suicide risk in clinical settings or designing and administering
      preventive interventions.

PMID- 21733213
TI  - Cool and hot executive functions in medication-naive attention deficit
      hyperactivity disorder children.
AB  - BACKGROUND: This study aimed to compare 'cool' [working memory (WM) and response
      inhibition] and 'hot' (delay aversion) executive functions (EFs) in children with
      and without attention deficit hyperactivity disorder (ADHD). METHOD: A total of
      100 ADHD children (45 with family history of ADHD and 55 with no family history)
      and 100 healthy controls, all medication free, were tested on tasks related to
      the 'hot' (i.e. two choice-delay tasks) and 'cool' domains of EF (i.e. Digits
      backward, Corsi Block Task backward, Go/No-Go Task, Stop-Signal Task, and the
      Stroop). RESULTS: Compared with the controls, children with ADHD were found to
      perform significantly worse on one or more measures of response inhibition, WM,
      and delay aversion after controlling for co-morbidities and estimated IQ. In
      addition, comparisons between ADHD children with family history of ADHD and those
      with no family history found significant differences on measures of response
      inhibition and WM but not delay aversion. These results are largely supported by
      results of two logistic regressions. CONCLUSIONS: ADHD was found to be associated
      with deficits on both cool and hot EFs. There is also evidence to suggest that
      cool EFs impairment is related to a family history of ADHD. Findings of this
      study have helped to elucidate the nature and extent of EF deficits in children
      with ADHD.

PMID- 21733214
TI  - Functional improvement and correlations with symptomatic improvement in adults
      with attention deficit hyperactivity disorder receiving long-acting
      methylphenidate.
AB  - BACKGROUND: Data on the relationship between core symptoms and daily functioning
      in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily
      functioning was assessed as part of an open-label extension, and associations
      with symptom scores were evaluated. METHOD: After a 5-week double-blind study
      with adults with ADHD receiving osmotic-controlled release oral delivery system
      (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were
      eligible for a 7-week open-label extension in which all patients received OROS
      MPH. Data for the Conners' Adult ADHD Rating Scale - Observer: Screening Version
      (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary
      endpoints included the observer self-reported short version of the CAARS (CAARS
      S:S) and the Clinical Global Impressions - Severity Scale (CGI-S). Daily
      functioning and quality of life were assessed using the Sheehan Disability Scale
      (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
      respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in
      subgroups. Relationships between symptom and functional outcomes were evaluated
      in a multivariate regression analysis. RESULTS: A total of 370 patients entered
      the open-label extension. Significant improvements from baseline in CAARS-O:SV
      were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co
      morbidity. Significant improvements from double-blind baseline were also seen for
      the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV
      Hyperactivity/Impulsivity subscale were associated with improvements in SDS total
      and subscale scores, and in the Q-LES-Q score at open-label endpoint.
      Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not
      significantly associated with functional changes. CONCLUSIONS: Improvements in
      ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS
      MPH are associated with improvements in daily functioning and quality of life.

PMID- 21733215
TI  - A randomized controlled trial of an Internet-based cognitive-behavioural skills
      package for carers of people with anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa (AN) poses a major burden on families. Carers (e.g.
      parents or partners) of people with AN are often highly distressed and may
      inadvertently respond in ways that can contribute to the maintenance of the
      disorder, e.g. through high levels of over-involvement and criticism [also known
      as expressed emotion (EE)]. This study aimed to evaluate the efficacy of a novel
      web-based systemic cognitive-behavioural (CBT) intervention for carers of people
      with AN, designed to reduce carer distress and teach skills in how to offer
      effective support. METHOD: Carers of people with AN (n=64) were randomly
      allocated to either the web-intervention, overcoming anorexia online, with
      limited clinician supportive guidance (by email or phone), or to ad-hoc usual
      support from the UK patient and carer organization Beat. Carer outcomes were
      assessed at post-treatment (4 months) and follow-up (6 months). RESULTS: Compared
      with the control intervention, web-based treatment significantly reduced carers'
      anxiety and depression (primary outcome) at post-treatment, with a similar trend
      in carers' EE. Other secondary outcomes did not favour the online intervention.
      Gains were maintained at follow-up. CONCLUSIONS: This is the first ever study to
      use an online CBT program to successfully reduce carer distress and improve
      carers' ability to support the person with AN.

PMID- 21733216
TI  - Prospective relationships of ADHD symptoms with developing substance use in a
      population-derived sample.
AB  - BACKGROUND: Clinically ascertained reports suggest that boys and girls with
      attention deficit hyperactivity disorder (ADHD) may differ from each other in
      their vulnerability to substance use problems. METHOD: A total of 1545 Finnish
      adolescents were assessed for DSM-IV-based ADHD symptoms by their parents and
      classroom teachers using standardized rating scales at age 11-12 years. At age
      14, substance use disorders and psychiatric co-morbidity were assessed with the
      Semi-Structured Assessment for the Genetics of Alcoholism, providing DSM-III
      R/DSM-IV diagnoses for Axis I disorders. At age 17.5, substance use was assessed
      by multi-item questionnaire. RESULTS: Although baseline ADHD symptoms were less
      common among females, they were more predictive of adverse substance use outcomes
      once conduct disorder and previous substance use were controlled for. Only in
      females were baseline ADHD symptoms significant predictors of alcohol abuse and
      dependence and illicit drug use at age 14. At the age of 17.5, parents' reports
      of inattentiveness and hyperactivity were significant predictors for frequent
      alcohol use in both sexes, but they were more predictive of frequent alcohol and
      illicit drug use in girls. Impulsivity in teachers' ratings predicted frequent
      alcohol use and illicit drug use in boys. Parental reports of inattentiveness in
      their 11-/12-year-old daughters were a consistent predictor for illicit drug use
      across adolescence. CONCLUSIONS: Inattentiveness and hyperactivity may be more
      predictive of alcohol use disorders and maladaptive patterns of alcohol and
      illicit drug use among girls than boys. The importance of these behavioural
      symptoms should be assessed further in the community, as they could jeopardize
      adolescents' successful transitioning into adult roles.

PMID- 21733217
TI  - Confirmation bias: why psychiatrists stick to wrong preliminary diagnoses.
AB  - BACKGROUND: Diagnostic errors can have tremendous consequences because they can
      result in a fatal chain of wrong decisions. Experts assume that physicians'
      desire to confirm a preliminary diagnosis while failing to seek contradictory
      evidence is an important reason for wrong diagnoses. This tendency is called
      'confirmation bias'. METHOD: To study whether psychiatrists and medical students
      are prone to confirmation bias and whether confirmation bias leads to poor
      diagnostic accuracy in psychiatry, we presented an experimental decision task to
      75 psychiatrists and 75 medical students. RESULTS: A total of 13% of
      psychiatrists and 25% of students showed confirmation bias when searching for new
      information after having made a preliminary diagnosis. Participants conducting a
      confirmatory information search were significantly less likely to make the
      correct diagnosis compared to participants searching in a disconfirmatory or
      balanced way [multiple logistic regression: odds ratio (OR) 7.3, 95% confidence
      interval (CI) 2.53-21.22, p<0.001; OR 3.2, 95% CI 1.23-8.56, p=0.02].
      Psychiatrists conducting a confirmatory search made a wrong diagnosis in 70% of
      the cases compared to 27% or 47% for a disconfirmatory or balanced information
      search (students: 63, 26 and 27%). Participants choosing the wrong diagnosis also
      prescribed different treatment options compared with participants choosing the
      correct diagnosis. CONCLUSIONS: Confirmatory information search harbors the risk
      of wrong diagnostic decisions. Psychiatrists should be aware of confirmation bias
      and instructed in techniques to reduce bias.

PMID- 21733218
TI  - Prevalence of psychiatric diagnoses in preterm and full-term children,
      adolescents and young adults: a meta-analysis.
AB  - BACKGROUND: Preterm (PT) birth and low birth weight (LBW) are high-prevalence
      events that are associated with adverse outcomes in the longer term, with
      vulnerability increasing as maturity at birth decreases. Psychiatric
      symptomatology appears heightened in PT/LBW survivors, though there are some
      discordant findings from studies using questionnaire measures, particularly with
      respect to anxiety and depressive symptoms. METHOD: This article synthesises
      findings from research using clinical psychiatric diagnostic criteria in PT/LBW
      individuals aged 10-25 years compared with term-born peers. Key outcomes of
      interest were the rates of individuals receiving any psychiatric diagnosis and
      the number of diagnoses of anxiety or depressive disorders. RESULTS: A literature
      search for studies reporting prevalence of 'any diagnosis' yielded five studies
      that met inclusion criteria, with a total of 565 PT/LBW and 533 control
      individuals. Also, five studies were found that reported rates of
      anxiety/depression (692 PT/LBW and 605 control individuals). The risk of these
      outcomes was increased for PT/LBW individuals compared with controls [any
      diagnosis: odds ratio (OR) 3.66, 95% confidence interval (CI) 2.57-5.21; anxiety
      or depressive disorder: OR 2.86, 95% CI 1.73-4.73]. CONCLUSIONS: The studies
      reviewed here indicate that, in addition to monitoring and management of medical
      and cognitive sequelae, the psychological well-being of PT/LBW individuals should
      be a key part of ongoing care.

PMID- 21733219
TI  - Daily cortisol, stress reactivity and psychotic experiences in individuals at
      above average genetic risk for psychosis.
AB  - BACKGROUND: Hypothalamic-pituitary-adrenocortical (HPA) axis abnormalities have
      been found in patients with a psychotic disorder and first-degree relatives of
      patients with a psychotic disorder react with subtle increases in non-clinical
      psychotic experiences and negative emotions in the face of everyday stress. The
      current study investigated whether HPA axis functioning is altered in individuals
      at above average genetic risk for psychotic disorder, examining diurnal cortisol
      profiles, cortisol reactivity to daily stressors and the association between HPA
      axis activity and subclinical psychotic experiences. METHOD: Participants
      included siblings of patients with a psychotic disorder (n=60) and a healthy
      comparison group (n=63). The Experience Sampling Method (a structured diary
      technique) was employed to assess stress, psychotic experiences, negative affect
      and salivary cortisol repeatedly in the flow of daily life. RESULTS: Multi-level
      analyses revealed higher diurnal cortisol levels and heightened cortisol
      reactivity to negative daily events in siblings compared with controls. Diurnal
      cortisol slope did not differ between the two groups, but momentary increases in
      psychotic experiences and negative affect were associated with increased cortisol
      in the sibling group. CONCLUSIONS: Findings support altered HPA axis activity in
      individuals at above average genetic risk for psychotic disorder, as evidenced by
      higher diurnal cortisol levels and increased cortisol reactivity to daily stress.
      Results also suggest a dynamic association between cortisol secretion and the
      intensity of psychotic-like experiences and negative emotions in daily life,
      although the direction of this association remains to be elucidated.

PMID- 21733220
TI  - Adiposity as a possible mediator of low testosterone salivary levels in
      adolescent boys in prodromal stages of psychosis.

PMID- 21733221
TI  - Decreased regional cerebral blood flow in medial prefrontal cortex during trauma
      unrelated stressful imagery in Vietnam veterans with post-traumatic stress
      disorder.
AB  - BACKGROUND: Neuroimaging research has demonstrated medial prefrontal cortex
      (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or
      emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few
      studies have examined brain responses to the recollection of stressful, but
      trauma-unrelated, personal events in PTSD. In the current study, we sought to
      determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and
      amygdala in PTSD could be observed during the recollection of trauma-unrelated
      stressful personal events. METHOD: Participants were 35 right-handed male combat
      veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven
      male, 10 female) with current military-related PTSD and 18 (nine male, nine
      female) with no current or lifetime PTSD. We used positron emission tomography
      (PET) and script-driven imagery to study rCBF during the recollection of trauma
      unrelated stressful versus neutral and traumatic events. RESULTS: Voxelwise tests
      revealed significant between-group differences for the trauma-unrelated stressful
      versus neutral comparison in mPFC, specifically in the anterior cingulate cortex
      (ACC). Functional region of interest (ROI) analyses demonstrated that this
      interaction in mPFC represented greater rCBF decreases in the PTSD group during
      trauma-unrelated stressful imagery relative to neutral imagery compared to the
      non-PTSD group. No differential amygdala activation was observed between groups
      or in either group separately. CONCLUSIONS: Veterans with PTSD, compared to those
      without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma
      unrelated stressful personal experiences. Functional neuroanatomical models of
      PTSD must account for diminished mPFC responses that extend to emotional stimuli,
      including stressful personal experiences that are not directly related to PTSD.

PMID- 21733222
TI  - Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are
      spectrum conditions? A family study perspective.
AB  - BACKGROUND: Experts have proposed removing obsessive-compulsive disorder (OCD)
      from the anxiety disorders section and grouping it with putatively related
      conditions in DSM-5. The current study uses co-morbidity and familiality data to
      inform these issues. METHOD: Case family data from the OCD Collaborative Genetics
      Study (382 OCD-affected probands and 974 of their first-degree relatives) were
      compared with control family data from the Johns Hopkins OCD Family Study (73 non
      OCD-affected probands and 233 of their first-degree relatives). RESULTS: Anxiety
      disorders (especially agoraphobia and generalized anxiety disorder), cluster C
      personality disorders (especially obsessive-compulsive and avoidant), tic
      disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder),
      grooming disorders (especially trichotillomania and pathological skin picking)
      and mood disorders (especially unipolar depressive disorders) were more common in
      case than control probands; however, the prevalences of eating disorders
      (anorexia and bulimia nervosa), other impulse-control disorders (pathological
      gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did
      not differ between the groups. The same general pattern was evident in relatives
      of case versus control probands. Results in relatives did not differ markedly
      when adjusted for demographic variables and proband diagnosis of the same
      disorder, though the strength of associations was lower when adjusted for OCD in
      relatives. Nevertheless, several anxiety, depressive and putative OCD-related
      conditions remained significantly more common in case than control relatives when
      adjusting for all of these variables simultaneously. CONCLUSIONS: On the basis of
      co-morbidity and familiality, OCD appears related both to anxiety disorders and
      to some conditions currently classified in other sections of DSM-IV.

PMID- 21733223
TI  - Drug-free patients with major depression show an increased electrophysiological
      response to valid and invalid feedback.
AB  - BACKGROUND: Depressed patients are biased in their response to negative
      information. They have been found to show a maladaptive behavioral and aberrant
      electrophysiological response to negative feedback. The aim of this study was to
      investigate the behavioral and electrophysiological response to feedback validity
      in drug-free depressed patients. METHOD: Fifteen drug-free in-patients with
      unipolar major depression disorder (MDD) and 30 demographically matched controls
      performed a time-estimation task in which they received valid and invalid (i.e.
      related and unrelated to performance) positive and negative feedback. The number
      of behavioral adjustments to the feedback and the feedback-related negativity
      (FRN) were measured. RESULTS: Patients made fewer correct adjustments after valid
      negative feedback than controls, and their FRNs were larger. Neither patients nor
      controls adjusted their time estimates following invalid negative feedback.
      CONCLUSIONS: The FRN results suggest that depressed drug-free in-patients have an
      atypical rostral anterior cingulate response to feedback that is independent of
      feedback validity. Their behavioral response to invalid negative feedback,
      however, is not impaired. This study confirms the notion that the behavioral
      responses of depressed individuals to negative feedback are context dependent.

PMID- 21733224
TI  - Testing the validity and acceptability of the diagnostic criteria for Hoarding
      Disorder: a DSM-5 survey.
AB  - BACKGROUND: The DSM-5 Obsessive-Compulsive Spectrum Sub-Workgroup is recommending
      the creation of a new diagnostic category named Hoarding Disorder (HD). The
      validity and acceptability of the proposed diagnostic criteria have yet to be
      formally tested. METHOD: Obsessive-compulsive disorder/hoarding experts and
      random members of the American Psychiatric Association (APA) were shown eight
      brief clinical vignettes (four cases meeting criteria for HD, three with hoarding
      behaviour secondary to other mental disorders, and one with subclinical hoarding
      behaviour) and asked to decide the most appropriate diagnosis in each case.
      Participants were also asked about the perceived acceptability of the criteria
      and whether they supported the inclusion of HD in the main manual. RESULTS:
      Altogether, 211 experts and 48 APA members completed the survey (30% and 10%
      response rates, respectively). The sensitivity and specificity of the HD
      diagnosis and the individual criteria were high (80-90%) across various types of
      professionals, irrespective of their experience with hoarding cases. About 90% of
      participants in both samples thought the criteria would be very/somewhat
      acceptable for professionals and sufferers. Most experts (70%) supported the
      inclusion of HD in the main manual, whereas only 50% of the APA members did.
      CONCLUSIONS: The proposed criteria for HD have high sensitivity and specificity.
      The criteria are also deemed acceptable for professionals and sufferers alike.
      Training of professionals and the development and validation of semi-structured
      diagnostic instruments should improve diagnostic accuracy even further. A field
      trial is now needed to confirm these encouraging findings with real patients in
      real clinical settings.

PMID- 21733225
TI  - Distinct periods of developmental sensitivity to the effects of 3,4-(+/-)
      methylenedioxymethamphetamine (MDMA) on behaviour and monoamines in rats.
AB  - Previous findings showed allocentric and egocentric learning deficits in rats
      after MDMA treatment from postnatal days (PD) 11-20 but not after treatment from
      PD 1-10. Shorter treatment periods (PD 1-5, 6-10, 11-15, or 16-20) resulted in
      allocentric learning deficits averaged across intervals but not for any interval
      individually and no egocentric learning deficits individually or collectively.
      Whether this difference was attributable to treatment length or age at the start
      of treatment was unclear. In the present experiment rat litters were treated on
      PD 1-10, 6-15, or 11-20 with 0, 10, or 15 mg/kg MDMA q.i.d. at 2-h intervals. Two
      male/female pairs/litter received each treatment. One pair/litter received
      acoustic startle with prepulse inhibition, straight channel swimming, Cincinnati
      water maze (CWM), and conditioned fear in a latent inhibition paradigm. The other
      pair/litter received locomotor activity, straight channel swimming, Morris water
      maze (MWM), and locomotor activity retest with MK-801 challenge. MDMA impaired
      CWM learning following PD 6-15 or 11-20 exposure. In MWM acquisition, all MDMA
      treated groups showed impairment. During reversal and shift, the PD 6-15 and PD
      11-20 MDMA-treated groups were significantly impaired. Reductions in locomotor
      activity were most evident after PD 6-15 treatment while increases in acoustic
      startle were most evident after PD 1-10 treatment. After MK-801 challenge, MDMA
      treated offspring showed less locomotion compared to controls. Region-specific
      changes in brain monoamines were also observed but were not significantly
      correlated with behavioural changes. The results show that PD 11-20 exposure to
      MDMA caused the largest long-term cognitive deficits followed by PD 6-15 exposure
      with PD 1-10 exposure least affected. Other effects, such as those upon MK-801
      stimulated locomotion showed greatest effects after PD 1-10 MDMA exposure. Hence,
      each effect has a different window of developmental susceptibility.

PMID- 21733226
TI  - The effect of clozapine on the AMPK-ACC-CPT1 pathway in the rat frontal cortex.
AB  - Clozapine is an antipsychotic drug that has a greater efficacy than other
      medications in some contexts, especially for the treatment of treatment-resistant
      schizophrenia. However, clozapine induces more metabolic side-effects involving
      abnormality in lipid metabolism compared to other antipsychotics. AMP-activated
      protein kinase (AMPK) plays a central role in controlling lipid metabolism
      through modulating the downstream acetyl CoA carboxylase (ACC) and carnitine
      palmitoyl transferase 1 (CPT1) pathway. In this study, we investigated the effect
      of a single intraperitoneal injection of clozapine on the AMPK-ACC-CPT1 pathway
      in the rat frontal cortex, which has been implicated as a target site for this
      antipsychotic drug. At 2 h after injection, the clinically relevant dose of
      clozapine had activated AMPK, with increased phosphorylation of AMPKalpha at
      Thr(172), and had inactivated ACC, with increased phosphorylation of ACC at
      Ser(79). In addition, clozapine activated the brain-specific isoform of CPT1,
      CPT1c, whose activity is inhibited by unphosphorylated ACC, in the rat frontal
      cortex. Immunohistochemistry and immunofluorescence analysis showed that
      clozapine induced an increase in number of p-AMPKalpha (Thr(172))- and p-ACC
      (Ser(79))-positive cells among the neurons of the rat frontal cortex. Taken
      together, these results show that clozapine activated the AMPK-ACC-CPT1 pathway
      in the neurons of the rat frontal cortex. These findings indicate that the
      antipsychotic agent clozapine affects the lipid regulatory system of neurons in
      the brain.

PMID- 21733227
TI  - Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val66Met
      polymorphism is associated with a better response to OROS-MPH in Korean ADHD
      children.
AB  - Research on psychostimulants, analysis of animal models and genetic association
      studies all suggest that the brain-derived neurotrophic factor gene (BDNF) may be
      a good candidate for pharmacogenetic studies of attention deficit hyperactivity
      disorder (ADHD). Yet to date there have been no pharmacogenetic studies of BDNF
      in ADHD. A total of 102 drug-naive ADHD children (8.7+/-2.1 yr) were treated with
      osmotic release oral system-methylphenidate (OROS-MPH) for 12 wk, and four kinds
      of response criteria were applied, based first, on a combined threshold of the
      ADHD Rating Scale - IV (ARS) and the Clinical Global Impression - Improvement
      scale (CGI-I); second, on scores of 1 or 2 vs. 3-7 on the CGI - Severity scale;
      third, on a >50% reduction in ARS scores; and fourth, on satisfaction of all of
      the aforementioned criteria. The Val66Met polymorphism of BDNF and six single
      nucleotide polymorphisms from the SLC6A2, ADRA2A and NTF-3 genes were tested for
      association with each criterion. Relative to other genotypes, homozygosity for
      the Val allele of the BDNF Val66Met polymorphism was associated with a greater
      relative frequency of good response under all four response criteria (after
      controlling for baseline ARS score, age, gender, final dose (mg/kg) of OROS-MPH
      at 12 wk, and level of academic functioning). This association was significant at
      the uncorrected level for the first and third response criteria (p=0.013 and
      p=0.018, respectively) and significant at a Bonferroni-corrected level for the
      second and fourth response criteria (p=0.0002, p=0.0003, respectively). Our
      findings support an association between homozygosity for the Val allele of BDNF
      and better response to OROS-MPH in Korean ADHD children as assessed by four
      different response criteria.

PMID- 21733228
TI  - Chronic modafinil effects on drug-seeking following methamphetamine self
      administration in rats.
AB  - Acute administration of the cognitive enhancing drug, modafinil (Provigil(r)),
      reduces methamphetamine (Meth) seeking following withdrawal from daily self
      administration. However, the more clinically relevant effects of modafinil on
      Meth-seeking after chronic treatment have not been explored. Here, we determined
      the impact of modafinil on Meth-seeking after chronic daily treatment during
      extinction or abstinence following Meth self-administration. Rats self
      administered intravenous Meth during daily 2-h sessions for 14 d, followed by
      extinction sessions or abstinence. During this period, rats received daily
      injections of vehicle, 30, or 100 mg/kg modafinil and were then tested for Meth
      seeking via cue, Meth-primed, and context-induced reinstatement at early and late
      withdrawal time-points. We found that chronic modafinil attenuated relapse to a
      Meth-paired context, decreased conditioned cue-induced and Meth-primed
      reinstatement, and resulted in enduring reductions in Meth-seeking even after
      discontinuation of treatment. Additionally, we determined that only a very high
      dose of modafinil (300 mg/kg) during maintenance of self-administration had an
      impact on Meth intake. These results validate and extend clinical and preclinical
      findings that modafinil may be a viable treatment option for Meth addiction.

PMID- 21733229
TI  - Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat
      brain: implications for its efficacy in bipolar disorder.
AB  - An up-regulated brain arachidonic acid (AA) cascade and a hyperglutamatergic
      state characterize bipolar disorder (BD). Lamotrigine (LTG), a mood stabilizer
      approved for treating BD, is reported to interfere with glutamatergic
      neurotransmission involving N-methyl-d-aspartate receptors (NMDARs). NMDARs allow
      extracellular calcium into the cell, thereby stimulating calcium-dependent
      cytosolic phospholipase A2 (cPLA2) to release AA from membrane phospholipid. We
      hypothesized that LTG, like other approved mood stabilizers, would reduce NMDAR
      mediated AA signalling in rat brain. An acute subconvulsant dose of NMDA (25
      mg/kg) or saline was administered intraperitoneally to unanaesthetized rats that
      had been treated p.o. daily for 42 d with vehicle or a therapeutically relevant
      dose of LTG (10 mg/kg.d). Regional brain AA incorporation coefficients k* and
      rates J in, and AA signals, were measured using quantitative autoradiography
      after intravenous [1-14C]AA infusion, as were other AA cascade markers. In
      chronic vehicle-treated rats, acute NMDA compared to saline increased k* and J in
      in widespread regions of the brain, as well as prostaglandin (PG)E2 and
      thromboxane B2 concentrations. Chronic LTG treatment compared to vehicle reduced
      brain cyclooxygenase (COX) activity, PGE2 concentration, and DNA-binding activity
      of the COX-2 transcription factor, NF-kappaB. Pretreatment with chronic LTG
      blocked the acute NMDA effects on AA cascade markers. In summary, chronic LTG
      like other mood stabilizers blocks NMDA-mediated signalling involving the AA
      metabolic cascade. Since markers of the AA cascade and of NMDAR signalling are up
      regulated in the post-mortem BD brain, mood stabilizers generally may be
      effective in BD by dampening NMDAR signalling and the AA cascade.

PMID- 21733230
TI  - Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of
      cognitively impaired phencyclidine-treated monkeys.
AB  - Schizophrenia patients, long-term abusers of phencyclidine (PCP), and monkeys
      treated with PCP all exhibit enduring cognitive deficits. Evidence indicates that
      loss of prefrontal cortex spine synapses results in cognitive dysfunction,
      suggesting the presence of synaptic pathology in the monkey PCP model; however,
      there is no direct evidence of such changes. In this study we use the monkey PCP
      model of schizophrenia to investigate at the ultrastructural level whether
      remodelling of dorsolateral prefrontal cortex (DLPFC) asymmetric spine synapses
      occurs following PCP. Subchronic PCP treatment resulted in a decrease in the
      number of asymmetric spine synapses, which was greater in layer II/III than layer
      V of DLPFC, compared to vehicle-treated controls. This decrease may contribute to
      PCP-induced cognitive dysfunction in the non-human primate model and perhaps in
      schizophrenia. Thus, the synapse loss in the PCP model provides a novel target
      for the development of potential treatments of cognitive dysfunction in this
      model and in schizophrenia.

PMID- 21733231
TI  - Effectiveness of psychotropic medications in the maintenance phase of bipolar
      disorder: a meta-analysis of randomized controlled trials.
AB  - The purpose of this meta-analysis was to examine the efficacy of maintenance
      treatments for bipolar disorder. Placebo-controlled or active comparator bipolar
      maintenance clinical trials of >=6 months' duration with at least 15
      patients/treatment group were identified using Medline, EMBASE,
      clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome
      measure was relative risk for relapse for patients in remission. Twenty trials
      (5,364 patients) were identified. Overall, lithium and quetiapine were the most
      studied agents (eight and five trials, respectively). The majority of studies
      included patients who had previously responded to treatment for an acute episode.
      All interventions, with the exception of perphenazine+mood stabilizer, showed a
      relative risk for manic/mixed or depressive relapse below 1.0, although there was
      variation in the statistical significance of the findings vs. placebo. No
      monotherapy was associated with a significantly reduced risk for both manic/mixed
      and depressed relapse. Of the combination treatments, only
      quetiapine+lithium/divalproex, was associated with a significantly reduced risk
      vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed
      and depressed poles of bipolar illness. Limitations for the analysis include
      differences in study durations and definitions of relapse. In conclusion,
      available maintenance therapies show considerable variation in efficacy. The
      efficacy of lithium and divalproex has been confirmed, but newer therapies, such
      as a number of atypical antipsychotics were also shown to be effective in bipolar
      disorder. Efficacy of all maintenance interventions needs to be balanced against
      the safety and tolerability profiles of individual agents.

PMID- 21733232
TI  - Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the
      anxiogenic effect of acute imipramine and fluoxetine administration.
AB  - A growing body of evidence indicates that facilitation of serotonin-2C receptor
      (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala
      (BLA) is involved in anxiety generation. We investigated here whether BLA 5
      HT2CRs exert a differential role in the regulation of defensive behaviours
      related to generalized anxiety (inhibitory avoidance) and panic (escape)
      disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the
      anxiogenic effect caused by acute systemic administration of the antidepressants
      imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze
      after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK
      212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of
      inhibitory avoidance acquisition and escape expression. We also investigated
      whether intra-BLA administration of SB-242084 interferes with the acute
      anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test,
      and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and
      MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic
      effect, SB-242084 had the opposite effect. None of these drugs affected escape
      performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully
      blocked the anxiogenic effect caused either by the local microinjection of 5-HT
      or the systemic administration of imipramine and fluoxetine. Our findings
      indicate that 5-HT2CRs in BLA are selectively involved in the regulation of
      defensive behaviours associated with generalized anxiety, but not panic. The
      results also provide the first direct evidence that activation of BLA 5-HT2CRs
      accounts for the short-term aversive effect of antidepressants. 

PMID- 21733233
TI  - Slow dissociation of partial agonists from the D2 receptor is linked to reduced
      prolactin release.
AB  - In this study we investigated the correlation between affinity, efficacy,
      peripheral receptor occupancy, and kinetic properties of D2 dopamine receptor
      ligands with time-course evaluations of prolactin release in rat blood. We
      profiled typical and atypical antipsychotic antagonists at D2 receptors, the
      partial agonist aripiprazole, and four novel partial agonist compounds with
      different properties. Clozapine and quetiapine revealed lower prolactin release
      and fast dissociation kinetics, linking fast dissociation and prolactin-sparing
      properties. Surprisingly, haloperidol, a highly prolactin-releasing antagonist,
      shared intermediate dissociation properties. Factors other than kinetic
      properties may thus contribute to prolactin-releasing properties of antagonists.
      Partial agonists sharing similar efficacies and receptor occupancies differed
      markedly in their ability to induce hyperprolactinaemia. Aripiprazole moderately
      released prolactin even at high receptor occupancies, with slow dissociation from
      D2 receptors. Other compounds displaying low affinities and fast dissociations
      released prolactin substantially, although less than haloperidol. The effect
      augmented after repeated administrations. Compounds with high affinities and slow
      dissociation rates stimulated moderate prolactin release at high receptor
      occupancies, reaching a ceiling effect at 50-60% occupancy. Moreover, the effect
      developed tolerance. In conclusion, we investigated the affinity and kinetic
      properties of D2 partial agonists associated with their ability to induce
      prolactin release in blood. We propose that for D2 partial agonists, at
      comparable intrinsic activities and peripheral occupancies, the prolactin
      releasing properties are linked to their kinetic rate properties. Differently
      from D2 antagonists, partial agonists display slow dissociation and high affinity
      associated with a low prolactin release profile.

PMID- 21733234
TI  - Evidence-based pharmacotherapy of panic disorder: an update.
AB  - The evidence-based pharmacotherapy of panic disorder continues to evolve. This
      paper reviews data on first-line pharmacotherapy, evidence for maintenance
      treatment, and management options for treatment-refractory patients. A Medline
      search of research on pharmacotherapy was undertaken, and a previous systematic
      review on the evidence-based pharmacotherapy of panic disorder was updated.
      Selective serotonin reuptake inhibitors remain a first-line pharmacotherapy of
      panic disorder, with the serotonin noradrenaline reuptake inhibitor venlafaxine
      also an acceptable early option. Temporary co-administration of benzodiazepines
      can be considered. Maintenance treatment reduces relapse rates, but further
      research to determine optimal duration is needed. For patients not responding to
      first-line agents several pharmacotherapy options are available, but there is a
      notable paucity of data on the optimal choice. 

PMID- 21733235
TI  - Acute administration of typical and atypical antipsychotics reduces EEG gamma
      power, but only the preclinical compound LY379268 reduces the ketamine-induced
      rise in gamma power.
AB  - A single non-anaesthetic dose of ketamine, a non-competitive NMDA receptor
      (NMDAR) antagonist with hallucinogenic properties, induces cognitive impairment
      and psychosis, and aggravates schizophrenia symptoms in patients. In conscious
      rats an equivalent dose of ketamine induces key features of animal models of
      acute psychosis, including hyperlocomotor activity, deficits in prepulse
      inhibition and gating of auditory evoked potentials, and concomitantly increases
      the power of ongoing spontaneously occurring gamma (30-80 Hz) oscillations in the
      neocortex. This study investigated whether NMDAR antagonist-induced aberrant
      gamma oscillations could be modulated by acute treatment with typical and
      atypical antipsychotic drugs. Extradural electrodes were surgically implanted
      into the skull of adult male Wistar rats. After recovery, rats were
      subcutaneously administered either clozapine (1-5 mg/kg, n=7), haloperidol (0.05
      0.25 mg/kg; n=8), LY379268 (a preclinical agonist at mGluR2/3 receptors: 0.3-3
      mg/kg; n=5) or the appropriate vehicles, and 30 min later received ketamine (5
      mg/kg s.c.). Quantitative measures of EEG gamma power and locomotor activity were
      assessed throughout the experiment. All three drugs significantly reduced the
      power of baseline EEG gamma oscillations by 30-50%, an effect most prominent
      after LY379268, and all inhibited ketamine-induced hyperlocomotor activity.
      However, only pretreatment with LY379268 attenuated trough-to-peak ketamine
      induced gamma hyperactivity. These results demonstrate that typical and atypical
      antipsychotic drugs acutely reduce cortical gamma oscillations, an effect that
      may be related to their clinical efficacy.

PMID- 21733236
TI  - The phosphodiesterase-4 inhibitor rolipram reverses Abeta-induced cognitive
      impairment and neuroinflammatory and apoptotic responses in rats.
AB  - beta-amyloid (Abeta) peptides play an important role in cognition deficits,
      neuroinflammation, and apoptosis observed in Alzheimer's disease (AD). Activation
      of cyclic AMP (cAMP) signalling enhances memory and inhibits inflammatory and
      apoptotic responses. However, it is not known whether inhibition of
      phosphodiesterase-4 (PDE4), a critical controller of intracellular cAMP
      concentrations, affects AD-associated neuroinflammatory and apoptotic responses
      and whether these responses contribute to deficits of memory mediated by cAMP
      signalling. We addressed these issues using memory tests and neurochemical
      measures. Specifically, rats microinfused with aggregated Abeta25-35 (10
      MUg/side) into bilateral CA1 subregions displayed deficits in learning ability
      and memory, as evidenced by decreases in escape latency during acquisition trials
      and exploratory activities in the probe trial in the water-maze task and 24-h
      retention in the passive avoidance test. These effects were reversed by rolipram
      (0.1, 0.25 and 0.5 mg/kg.d i.p.), a prototypic PDE4 inhibitor, in a dose
      dependent manner. Interestingly, Abeta25-35-treated rats also displayed decreases
      in expression of phosphorylated cAMP response-element binding protein (pCREB) and
      Bcl-2, but increases in expression of NF-kappaB p65 and Bax in the hippocampus;
      these effects were also reversed by rolipram in a dose-dependent manner. Similar
      neurochemical results were observed by replacing Abeta25-35 with Abeta1-42, a
      full-length amyloid peptide that quickly forms toxic oligomers. These results
      suggest that PDE4 inhibitors such as rolipram may reverse Abeta-induced memory
      deficits at least in part via the attenuation of neuronal inflammation and
      apoptosis mediated by cAMP/CREB signalling. PDE4 could be a target for treatment
      of memory loss associated with AD.

PMID- 21733237
TI  - Mouse strain differences in phencyclidine-induced behavioural changes.
AB  - Administration of phencyclidine (PCP) is acknowledged to generate a model of
      psychosis in animals. With the identification of genetic susceptibility factors
      for schizophrenia and bipolar disorder, great efforts have been made to generate
      genetic animal models for major mental illnesses. As these disorders are
      multifactorial, comparisons among drug-induced (non-genetic) and genetic models
      are becoming an important issue in biological psychiatry. A major barrier is that
      the standard mouse strain used in the generation of genetic models is C57BL/6,
      whereas almost all studies with PCP-induced models have utilized other strains.
      To fill this technical gap, we systematically compared the behavioural changes
      upon PCP administration in different mouse strains, including C57BL/6N, C57BL/6J,
      ddY, and ICR. We observed strain differences in PCP-induced hyperlocomotion and
      enhanced immobility in the forced swim test (ddY>>C57BL/6N and 6J>ICR). In
      contrast, there was no strain difference in the impairment of recognition memory
      in the novel object recognition memory test after withdrawal of chronic PCP
      administration. This study provides practical guidance for comparing genetic with
      PCP-induced models of psychosis in C57BL/6. Furthermore, such strain differences
      may provide a clue to the biological mechanisms underlying PCP-induced
      endophenotypes possibly relevant to major mental illnesses.

PMID- 21733238
TI  - Modulation of neuroplasticity pathways and antidepressant-like behavioural
      responses following the short-term (3 and 7 days) administration of the 5-HT4
      receptor agonist RS67333.
AB  - It has been recently suggested that activation of 5-HT4 receptors might exert
      antidepressant-like effects in rats after 3 d treatment, suggesting a new
      strategy for developing faster-acting antidepressants. We studied the effects of
      3 d and 7 d treatment with the 5-HT4 receptor partial agonist RS67333 (1.5
      mg/kg.d) in behavioural tests of chronic efficacy and on neuroplastic-associated
      changes, such as adult hippocampal neurogenesis, expression of CREB, BDNF, beta
      catenin, AKT and 5-HT4 receptor functionality. RS67333 treatment up-regulated
      hippocampal cell proliferation, beta-catenin expression and pCREB/CREB ratio
      after 3 d treatment. This short-term treatment also reduced immobility time in
      the forced swim test (FST), together with a partial reversion of the anhedonic
      like state (sucrose consumption after chronic corticosterone). Administration of
      RS67333 for 7 d resulted in a higher increase in the rate of hippocampal cell
      proliferation, a significant desensitization of 5-HT4 receptor-coupled adenylate
      cyclase activity and a more marked increase in the expression of neuroplasticity
      related proteins (BDNF, CREB, AKT): these changes reached the same magnitude as
      those observed after 3 wk administration of classical antidepressants.
      Consistently, a positive behavioural response in the novelty suppressed feeding
      (NSF) test and a complete reversion of the anhedonic-like state (sucrose
      consumption) were also observed after 7 d treatment. These results support the
      antidepressant-like profile of RS67333 with a shorter onset of action and suggest
      that this time period of administration (3-7 d) could be a good approximation to
      experimentally predict the onset of action of this promising strategy.

PMID- 21733239
TI  - Hypothalamus and pituitary volume in schizophrenia: a structural MRI study.
AB  - Volumetric differences of the hypothalamus and/or the pituitary gland tend to
      support involvement of the HPA axis in psychotic disorders. These structures were
      manually outlined in 154 schizophrenia patients and 156 matched healthy
      comparison subjects by MRI brain images. Linear regression analyses were
      performed to investigate differences in volume between groups. Moreover, the
      effects of illness duration and type of medication were investigated. No
      significant differences were found between patients and healthy controls in
      volumes of the hypothalamus and pituitary gland. In addition, there were no
      differences in volumes between patients with short and long illness duration.
      There was a trend towards patients receiving typical antipsychotic medication at
      the time of scanning having larger pituitary volumes than patients receiving
      atypical medication. These findings indicate that volume decreases in brain
      structures important for the normal functioning of the HPA axis are not present,
      either in recent-onset or chronically ill patients.

PMID- 21733240
TI  - Vagus nerve stimulation enhances perforant path-CA3 synaptic transmission via the
      activation of beta-adrenergic receptors and the locus coeruleus.
AB  - Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and
      depression and has cognition-enhancing effects in patients with Alzheimer's
      disease. The hippocampus is widely recognized to be related to epilepsy,
      depression, and Alzheimer's disease. One possible mechanism of VNS involves its
      effect on the hippocampus; i.e. it increases the release of noradrenaline in the
      hippocampus. However, the effect of VNS on synaptic transmission in the
      hippocampus is unknown. To determine whether VNS modulates neurotransmission in
      the hippocampus, we examined the effects of VNS on perforant path (PP)-CA3
      synaptic transmission electrophysiologically in anaesthetized rats. VNS induces a
      persistent enhancement of PP-CA3 field excitatory post-synaptic potentials
      (fEPSPs). Arc, an immediate early gene, was used to identify active brain regions
      after VNS. The locus coeruleus (LC), which contains the perikarya of
      noradrenergic projections, harboured more Arc-positive cells, as measured by in
      situ hybridization, after 10-min VNS. In addition, electrical lesions of LC
      neurons or intraventricular administration of the beta-adrenergic receptor
      antagonist timolol prevented the enhancement of PP-CA3 responses by VNS. In
      conclusion, the protracted increase in PP-CA3 synaptic transmission that is
      induced by VNS entails activation of the LC and beta-adrenergic receptors. Our
      novel findings suggest that information from the periphery modulates synaptic
      transmission in the CA3 region of the hippocampus.

PMID- 21733241
TI  - Molecular adaptation to chronic antidepressant treatment: evidence for a more
      rapid response to the novel alpha2-adrenoceptor antagonist/5-HT-noradrenaline
      reuptake inhibitor (SNRI), S35966, compared to the SNRI, venlafaxine.
AB  - Evidence of early changes in neural plasticity may aid the prediction of rapid
      onset antidepressant drugs. Here we compared the dual alpha2-adrenoceptor
      antagonist/5-HT-noradrenaline reuptake inhibitor (SNRI), S35966, to the SNRI,
      venlafaxine, with regards to their effect on rat brain expression of a panel of
      neural plasticity-related genes: Arc, BDNF, and VGLUT1, as well as Homer1a and
      Shank1B (not studied previously). Abundance of mRNA was determined by in-situ
      hybridization in cortical and hippocampal regions 2 h and 16 h following drug
      administration for 14, 7 and 1 d. After 14 d, both S35966 and venlafaxine
      increased mRNA of all genes, including Homer1a and Shank1B, and effects were
      similarly time- and region-dependent. After 7 d, S35966 elevated Arc, Shank1B and
      BDNF mRNA, whereas venlafaxine increased Shank1B mRNA only. Finally, after 1 d
      (acute administration), S35966 increased Arc and Homer1a mRNA whereas venlafaxine
      had no effect on any gene examined. In summary, a 14-d course of treatment with
      S35966 or venlafaxine induced similar region- and time-dependent increases in
      expression of neural plasticity-related genes including Shank1B and Homer1a. Some
      genes responded earlier to S35966, suggesting that drugs with combined alpha2
      adrenoceptor antagonist/SNRI properties may elicit more rapid changes in markers
      of neural plasticity than a SNRI alone.

PMID- 21733242
TI  - Increase of antipsychotic medication in depressive inpatients from 2000 to 2007:
      results from the AMSP International Pharmacovigilance Program.
AB  - While international guidelines recommend monotherapy with antidepressants for
      depressed patients, recent investigation has demonstrated augmenting effects of
      antipsychotics (APs) in patients with major depression. We set out to investigate
      the use of APs in a European sample of depressed inpatients and the possible
      changes in their prescription over the period from 2000 to 2007. On two reference
      days in the years 2000 (32 psychiatric institutions, N=1078) and 2007 (54
      psychiatric institutions, N=1826), the following data were recorded for all
      depressed inpatients (ICD-10: F32.00, F32.01, F32.1, F32.10, F32.11, F32.2,
      F33.0, F33.00, F33.01, F33.1, F33.10, F33.11, F33.2), monitored as part of the
      AMSP (Arzneimittelsicherheit in der Psychiatrie) surveillance programme: age,
      sex, ICD-10 diagnosis and all medication applied on that day. Depressed
      inpatients with psychotic symptoms were excluded. We found a significant increase
      in the number of AP-treated inpatients from 37.9% in 2000 to 45.8% in 2007
      (chi2=17.257, p<0.001). The number of inpatients who received an atypical AP rose
      significantly between 2000 and 2007, from 12.8% to 28.3% (chi2=93.37, p<0.001).
      On the contrary, the percentage of inpatients receiving typical APs showed a
      significant decrease from 30.2% to 24.1% over the same period (chi2=13.179,
      p<0.001). Examining only the subgroup of severely depressed inpatients we found
      an increase in the number of AP-treated inpatients, but this was not
      statistically significant (chi2=2.047, p=0.15). Our study revealed a significant
      increase in the usage of atypical APs. However, this effect was not only due to
      augmentation strategies for severely depressed inpatients. Further studies are
      needed to examine possible putative effects of AP augmentation treatment in mild
      to moderate depression.

PMID- 21733243
TI  - Mood dysregulation and stabilization: perspectives from emotional cognitive
      neuroscience.
AB  - Mood is conceptualized as a long-lasting emotional state, which can have profound
      implications for mental and physical health. The development of neuroimaging
      methods has enabled significant advances towards elucidating the mechanisms
      underlying regulation of mood and emotion; however, our understanding of mood and
      emotion dysregulation in stress-related psychiatric disorders is still largely
      lacking. From the cognitive-affective neuroscience perspective, achieving deeper,
      more mechanistic understanding of mood disorders necessitates detailed
      understanding of specific components of neural systems involved in mood
      dysregulation and stabilization. In this review, we provide an overview of neural
      systems implicated in the development of a long-term negative mood state, as well
      as those related to emotion and emotion regulation, and discuss their proposed
      involvement in mood and anxiety disorders.

PMID- 21733244
TI  - Prefrontal cortex glutathione S-transferase levels in patients with bipolar
      disorder, major depression and schizophrenia.
AB  - Antioxidant defence systems have received increasing attention in the
      pathophysiology of psychiatric disorders, including: bipolar disorder (BD), major
      depressive disorder (MDD), and schizophrenia (SCZ). Recently, we reported
      decreased glutathione (GSH) levels in post-mortem prefrontal cortex from patients
      with BD, MDD, and SCZ. To explore this further, we evaluated the levels of two
      glutathione S-transferase (GST) isoforms via immunoblotting: GST Pi and GST Mu.
      GST Pi levels were not affected in any of the patients groups vs. controls. GST
      Mu levels were significantly decreased in patients with MDD and SCZ but not BD.
      Compared to controls, GST Mu levels were not different in BD patients who had
      been treated with mood stabilizers at the time of death but were significantly
      lower in those not taking mood stabilizers at the time of death. These data
      suggest that GST Mu may be a target for mood stabilizers.

PMID- 21733245
TI  - Neuron density and serotonin receptor binding in prefrontal cortex in suicide.
AB  - Although serotonin receptor and cytoarchitectonic alterations are reported in
      prefrontal cortex (PFC) in suicide and depression, no study has considered
      binding relative to neuron density. Therefore, we measured neuron density and
      serotonin transporter (SERT), 5-HT1A and 5-HT2A binding in matched suicides and
      controls. Suicides and normal controls (n=15 matched pairs) were psychiatrically
      characterized. Neuron density and binding were determined in dorsal [Brodmann
      area (BA) 9] and ventral (BA 47) PFC by stereology and quantitative
      autoradiography in near-adjacent sections. Binding index was defined as the ratio
      of receptor binding to neuron density. Suicides had lower neuron density in the
      gyrus of both areas. The binding index was lower for SERT in BA 47 but not in
      BA9; the 5-HT1A binding index was higher in BA 9 but not in BA 47, while the 5
      HT2A binding index was not different between groups. SERT binding was lower in
      suicides in BA 47 but not BA 9, while 5-HT1A binding was higher in BA 9 but not
      BA 47. SERT binding negatively correlated with 5-HT1A binding in BA 47 in
      suicides. Neuron density decreased with age. The 5-HT1A binding index was higher
      in females than males. We found lower neuron density and lower SERT binding index
      in both PFC regions in suicides. More 5-HT1A binding with less SERT binding and
      the negative correlation in depressed suicides suggests post-synaptic receptor up
      regulation, and it is independent of the difference in neuron density. Thus,
      abnormalities in both cortical neurons and in their serotonergic innervation are
      present in suicides and future studies will need to determine whether cortical
      changes reflect the trophic effect of altered serotonin innervation.

PMID- 21733246
TI  - The role of drinking water in the transmission of antimicrobial-resistant E.
      coli.
AB  - To determine whether drinking water contaminated with antimicrobial-resistant E.
      coli is associated with the carriage of resistant E. coli, selected households
      sending water samples to Ontario and Alberta laboratories in 2005-2006 were asked
      to participate in a cross-sectional study. Household members aged >=12 years were
      asked to complete a questionnaire and to submit a rectal swab. In 878
      individuals, 41% carried a resistant strain of E. coli and 28% carried a
      multidrug-resistant strain. The risk of carriage of resistant E. coli was 1.26
      times higher for users of water contaminated with resistant E. coli. Other risk
      factors included international travel [prevalence ratio (PR) 1.33], having a
      child in nappies (PR 1.33), being male (PR 1.33), and frequent handling of raw
      red meats (PR 1.10). Protecting private water sources (e.g. by improving systems
      to test and treat them) may help slow the emergence of antimicrobial resistance
      in E. coli.

PMID- 21733247
TI  - Trend of hospital utilization for encephalitis.
AB  - Encephalitis generally results in a serious illness requiring hospitalization.
      The aim of this study was to describe the epidemiology of hospitalization for
      encephalitis in Italy, taking into account the geographical distribution,
      aetiology, seasonality and evolution of hospitalization rates over recent years.
      The mean hospitalization rate was 5.88/100 000. For most of these
      hospitalizations (n=13 119, 55.6%), no specific cause of encephalitis was
      reported. The most common aetiological category was 'viral', which accounted for
      40.1% (n=4205) of such hospitalizations (rate 1.05/100 000). Within this
      category, herpes virus was the leading causative agent (n=1579, 0.39/100 000).
      This report highlights a significant increase of 'viral encephalitis not
      otherwise specified' (ICD-9 code 049.9) vs. a reduction of all other causes. A
      seasonal pattern was noted in people aged >=65 years in this group. Specific
      surveillance of encephalitis without known origin should be reinforced in order
      to identify the potential role of emerging pathogens and to design preventive
      interventions.

PMID- 21733248
TI  - Risk factors for mortality in non-pregnancy-related listeriosis.
AB  - We examined non-pregnancy-related listeriosis cases in England and Wales reported
      to the Health Protection Agency between 1990 and 2009 (n=1864) using
      unconditional multivariate logistic regression analysis to identify factors
      independently associated with mortality. A subset analysis of cases between 2005
      and 2009 (n=694) investigated the additional effect of antibiotic therapy on
      survival. In these cases particular malignancies, alcoholism, cardiovascular
      disease, increasing age, and treatment to reduce gastric acid secretion were
      positively associated with mortality. The absence of a concurrent condition and
      presence of autoimmune disease had a protective effect. The subset analysis
      identified illness in winter or spring as a risk factor and antibiotic therapy as
      a protective factor for mortality. The impact of antibiotic therapy, seasonality
      and reduced gastric acid status on survival should be further investigated.
      Policy-makers and clinicians need to more broadly advise those at risk of
      contracting this disease and dying as a consequence.

PMID- 21733249
TI  - Collecting close-contact social mixing data with contact diaries: reporting
      errors and biases.
AB  - The analysis of contact networks plays a major role to understanding the dynamics
      of disease spread. Empirical contact data is often collected using contact
      diaries. Such studies rely on self-reported perceptions of contacts, and
      arrangements for validation are usually not made. Our study was based on a
      complete network study design that allowed for the analysis of reporting accuracy
      in contact diary studies. We collected contact data of the employees of three
      research groups over a period of 1 work week. We found that more than one third
      of all reported contacts were only reported by one out of the two involved
      contact partners. Non-reporting is most frequent in cases of short, non-intense
      contact. We estimated that the probability of forgetting a contact of <=5 min
      duration is greater than 50%. Furthermore, the number of forgotten contacts
      appears to be proportional to the total number of contacts.

PMID- 21733250
TI  - Prevalence and growth kinetics of Shiga toxin-producing Escherichia coli (STEC)
      in bovine offal products in Japan.
AB  - Recent epidemiological data suggest a link between the consumption of bovine
      offal products and Shiga toxin-producing Escherichia coli (STEC) infection in
      Japan. This study thus examined the prevalence of STEC in various types of these
      foods. PCR screened 229 bovine offal products for the presence of Shiga toxin
      (stx) gene. Thirty-eight (16.6%) samples were stx positive, of which eight were
      positive for rfbE(O157) and three were positive for wzy(O26). Four O157 and one
      O26 STEC isolates were finally obtained from small-intestine and omasum products.
      Notably, homogenates of bovine intestinal products significantly reduced the
      extent of growth of O157 in the enrichment process compared to homogenates of
      beef carcass. As co-incubation of O157 with background microbiota complex from
      bovine intestinal products in buffered peptone water, in the absence of meat
      samples, tended to reduce the extent of growth of O157, we reasoned that certain
      microbiota present in offal products played a role. In support of this,
      inoculation of generic E. coli from bovine intestinal products into the
      homogenates significantly reduced the extent of growth of O157 in the homogenates
      of bovine intestinal and loin-beef products, and this effect was markedly
      increased when these homogenates were heat-treated prior to inoculation.
      Together, this report provides first evidence of the prevalence of STEC in a
      variety of bovine offal products in Japan. The prevalence data herein may be
      useful for risk assessment of those products as a potential source of human STEC
      infection beyond the epidemiological background. The growth characteristic of
      STEC O157 in offal products also indicates the importance of being aware when to
      test these food products.

PMID- 21733251
TI  - Under-recognition and reporting of dengue in Cambodia: a capture-recapture
      analysis of the National Dengue Surveillance System.
AB  - Robust disease burden estimates are important for decision-making concerning
      introduction of new vaccines. Dengue is a major public health problem in the
      tropics but robust disease burden estimates are lacking. We conducted a two
      sample, capture-recapture study in the largest province in Cambodia to determine
      disease under-recognition to the National Dengue Surveillance System (NDSS).
      During 2006-2008, community-based active surveillance for acute febrile illness
      was conducted in 0- to 19-year-olds in rural and urban areas combined with
      testing for dengue virus infection. Of 14 354 individuals under active
      surveillance (22 498 person-seasons), the annual incidence ranged from 13.4 to
      57.8/1000 person-seasons. During the same period, NDSS incidence rates ranged
      from 1.1/1000 to 5.7/1000, which was 3.9- to 29.0-fold lower than found in the
      capture-recapture study. In hospitalized cases, the rate of under-recognition was
      1.1- to 2.4-fold. This study shows the substantial degree of under
      recognition/reporting of dengue and that reported hospitalized cases are not a
      good surrogate for estimating dengue disease burden.

PMID- 21733252
TI  - Epidemiological and clinical aspects of human Brucella suis infection in
      Polynesia.
AB  - High brucellosis seroprevalence rates in domestic swine herds have been reported
      in Wallis and Futuna Islands and are associated with a significant burden of
      human infection by Brucella suis, a species that is rarely incriminated in human
      disease. Between 2003 and 2010, seven patients had a positive blood culture for
      B. suis biovar 1, 11 symptomatic patients had a positive Rose Bengal test (RBT)
      and a positive serum agglutination test (SAT) and three asymptomatic cases were
      found to be positive for RBT, SAT or ELISA IgM (after systematic screening of 52
      family members of 15 index cases). Overall, Brucella infection was diagnosed in
      21 people, corresponding to a mean annual incidence of 19 cases/100 000
      inhabitants. Compared to series of patients infected with other more commonly
      encountered Brucella spp. such as B. melitensis and B. abortus, clinical
      presentation and percentage and distribution of complications were similar, apart
      from a marked observation of significantly increased median alanine
      aminotransferase levels, 20 times greater than upper normal rates, but not
      accompanied by any particular hepatic pathology. Wallis and Futuna, where people
      live in close proximity to animals and where the cultural significance of pig
      raising precludes the implementation of adequate veterinary preventive measures,
      thus represents one of the few known B. suis foci worldwide and allows for
      evaluation of the peculiarities of this infection.

PMID- 21733253
TI  - Acinetobacter calcoaceticus-Acinetobacter baumannii complex species in clinical
      specimens in Singapore.
AB  - This study was performed to determine the prevalence, distribution of specimen
      sources, and antimicrobial susceptibility of the Acinetobacter calcoaceticus
      Acinetobacter baumannii (Acb) species complex in Singapore. One hundred and
      ninety-three non-replicate Acb species complex clinical isolates were collected
      from six hospitals over a 1-month period in 2006. Of these, 152 (78.7%) were
      identified as A. baumannii, 18 (9.3%) as 'Acinetobacter pittii' [genomic species
      (gen. sp.) 3], and 23 (11.9%) as 'Acinetobacter nosocomialis' (gen. sp. 13TU).
      Carbapenem resistance was highest in A. baumannii (72.4%), followed by A. pittii
      (38.9%), and A. nosocomialis (34.8%). Most carbapenem-resistant A. baumannii and
      A. nosocomialis possessed the bla(OXA-23-like) gene whereas carbapenem-resistant
      A. pittii possessed the bla(OXA-58-like) gene. Two imipenem-resistant strains (A.
      baumannii and A. pittii) had the bla(IMP-like) gene. Representatives of
      carbapenem-resistant A. baumannii were related to European clones I and II.

PMID- 21733254
TI  - Paediatric intensive care admissions for respiratory syncytial virus
      bronchiolitis in France: results of a retrospective survey and evaluation of the
      validity of a medical information system programme.
AB  - The purpose of this study was to describe the characteristics of patients with
      bronchiolitis admitted to a paediatric intensive care unit (PICU), and to
      evaluate a national registry of hospitalizations (Programme de Medicalisation des
      Systemes d'Information; PMSI) as a potential source of epidemiological data. Of
      the 49 French PICUs invited to take part in a retrospective survey of children
      aged <2 years who were hospitalized during the 2005-2006 epidemic season, 24
      agreed to participate. Overall, 467 children were enrolled: 75% were aged <2
      months, 76% had positive respiratory syncytial virus (RSV) tests, 34.9% required
      non-invasive ventilation, 36.6% were mechanically ventilated, and six infants
      died. The main neonatal characteristics were: prematurity (31.9%), respiratory
      disease (16.5%), congenital heart disease (6.4%), receiving mechanical
      ventilation (11.6%), and bronchopulmonary dysplasia at day 28 (3.8%). For
      bronchiolitis episode, the kappa coefficient between the survey and PMSI data was
      good only for mechanical ventilation (0.63) and the death rate (0.86).

PMID- 21733255
TI  - The epidemiology of sporadic human infections with unusual cryptosporidia
      detected during routine typing in England and Wales, 2000-2008.
AB  - Routine typing of 14 469 isolates from human cryptosporidiosis cases between 2000
      and 2008 revealed that 7439 (51.4%) were Cryptosporidium (C.) hominis, 6372
      (44.0%) C. parvum, 51 (0.4%) both C. hominis and C. parvum, 443 (3.1%) were not
      typable and 164 (1.1%) were other Cryptosporidium species or genotypes. Of the
      latter, 109 were C. meleagridis, 38 C. felis, 11 C. ubiquitum, one C. canis, two
      horse, two novel and one skunk genotype. C. hominis monkey genotype and C.
      cuniculus were identified in a separate study. Patients with unusual infections
      were older than those with C. hominis (P<0.01) or C. parvum (P<0.01) and were
      more likely to be immunocompromised (Fisher's exact P<0.01). Forty-one percent of
      unusual cases had travelled abroad, mainly to the Indian subcontinent.
      Significant risk factors in those with unusual species were travel abroad (C.
      meleagridis, P<0.01), being immunocompromised (C. felis, Fisher's exact P=0.02),
      and contact with cats (C. felis, Fisher's exact P=0.02).

PMID- 21733256
TI  - Geographical gradient of mean age of dengue haemorrhagic fever patients in
      northern Thailand.
AB  - Dengue haemorrhagic fever (DHF) is caused by dengue virus transmitted by Aedes
      mosquitoes; mean age of patients varies temporally and geographically.
      Variability in age of patients may be due to differences in transmission
      intensity or demographic structure. To compare these two hypotheses, the mean age
      of DHF patients from 90 districts in northern Thailand (1994-1996, 2002-2004) was
      regressed against (i) Aedes abundance or (ii) demographic variables (birthrate,
      average age) of the district. We also developed software to quantify direction
      and strength of geographical gradients of these variables. We found that, after
      adjusting for socioeconomics, climate, spatial autocorrelation, the mean age of
      patients was correlated only with Aedes abundance. The geographical gradient of
      mean age of patients originated from entomological, climate, and socioeconomic
      gradients. Vector abundance was a stronger determinant of mean age of patients
      than demographic variables, in northern Thailand.

PMID- 21733257
TI  - Eradication and control of livestock ticks: biological, economic and social
      perspectives.
AB  - Comparisons of successful and failed attempts to eradicate livestock ticks reveal
      that the social context of farming and management of the campaigns have greater
      influence than techniques of treatment. The biology of ticks is considered
      principally where it has contributed to control of ticks as practiced on farms.
      The timing of treatments by life cycle and season can be exploited to reduce
      numbers of treatments per year. Pastures can be managed to starve and desiccate
      vulnerable larvae questing on vegetation. Immunity to ticks acquired by hosts can
      be enhanced by livestock breeding. The aggregated distribution of ticks on hosts
      with poor immunity can be used to select animals for removal from the herd.
      Models of tick population dynamics required for predicting outcomes of control
      methods need better understanding of drivers of distribution, aggregation,
      stability, and density-dependent mortality. Changing social circumstances,
      especially of land-use, has an influence on exposure to tick-borne pathogens that
      can be exploited for disease control.

PMID- 21733258
TI  - Geographical and host distribution patterns of Parvicapsula minibicornis
      (Myxozoa) small subunit ribosomal RNA genetic types.
AB  - Parvicapsula minibicornis is a myxozoan parasite implicated in mortalities of
      both juvenile and pre-spawning adult salmon in the Pacific Northwest of North
      America. Disease severity and presentation varies between salmon species and
      geographical localities. To better characterize population structure of the
      parasite, we sought genetic markers in the P. minibicornis ribosomal RNA gene. We
      compared samples from California with the type specimen from British Columbia,
      identified sequence variations, and then sequenced 197 samples from fish, river
      water and the parasite's polychaete worm host. Although DNA sequences of the
      parasite were >98.9% similar, there was enough variation to define 15 genotypes.
      All genotypes were detected in fish samples, although not in all species. A
      single genotype only was found in sockeye and pink salmon in the Fraser River
      Basin, but was not detected in sockeye from the adjacent Columbia River Basin.
      All coho salmon, irrespective of river basin, were infected with a unique mix of
      2 genotypes. These data indicated that the P. minibicornis population exhibited
      strong signals of structuring by both geography and salmonid host species.
      Particular genotypes may correlate with disease differences seen in salmon
      populations in the Pacific Northwest.

PMID- 21733259
TI  - Differential virulence in two congeneric ticks infesting songbird nestlings.
AB  - Virulence is part of the proximate base to the understanding of host-parasite
      interactions, and therefore it is crucial to interpret parasite-induced damage as
      an outcome of co-evolution between parasite and host. We experimentally
      investigated the impact of 2 congeneric ticks with contrasting transmission modes
      and host specificity, on the health of songbird nestlings (Parus major). The
      nidicolous Ixodes arboricola lives in tree holes where it obtains blood from
      adult birds and their nestlings, hence is prone to vertical transmission. All
      developmental stages of the field-dwelling Ixodes ricinus feed on different host
      taxa, hence are prone to horizontal transmission. Within each nest we infested 3
      nestlings with varying loads of I. ricinus and 3 with Ixodes arboricola. Ixodes
      arboricola had no negative effects on nestling health (haematocrit, inflammation,
      body size, body condition). Body size was positively associated with the number
      of feeding I. arboricola adults. In contrast, I. ricinus infestations by nymphs
      and adult ticks led to haematocrit reductions. Furthermore, I. arboricola was a
      more prudent feeder, with longer feeding durations for smaller bloodmeals.
      Although the negative effects on nestling health were limited, our results are in
      line with current theories, stating that virulence increases with horizontal
      transmission, reduced dependence on individual hosts and reduced relatedness
      among co-exploiting ticks.

PMID- 21733260
TI  - Host-parasite interactions and global climate oscillations.
AB  - It is suspected that host-parasite interactions are influenced by climatic
      oscillations such as the North Atlantic Oscillation (NAO). However, the effects
      of climatic oscillations on host-parasite interactions have never been
      investigated. A long-term (1982-1999) dataset of the host snail Lymnaea stagnalis
      and trematode metacercariae infection has been collected for Lake Chany in
      Western Siberia. Using this dataset, we estimated the impact of the NAO on the
      population dynamics of hosts and parasites as well as their interactions. The
      results of general linear models showed that the abundance of dominant parasite
      species and the total parasite abundance significantly increased with NAO, with
      the exception of Moliniella anceps. Other climatic and biological factors were
      relatively weak to explain the abundance. There was no significant relationship
      between NAO and the population density of host snails. The prevalence of
      infection was related to the total abundance of parasites, but not to the NAO.
      Thus, the responses to the NAO differed between the host and parasites,
      indicating mismatching in host-parasite interactions. Therefore, climatic
      oscillations, such as the NAO, influence common parasitism.

PMID- 21733261
TI  - Environmental constraints influencing survival of an African parasite in a north
      temperate habitat: effects of temperature on development within the host.
AB  - The monogenean Protopolystoma xenopodis has been established in Wales for >40
      years following introduction with Xenopus laevis from South Africa. This provides
      an experimental system for determining constraints affecting introduced species
      in novel environments. Parasite development post-infection was followed at 15, 20
      and 25 degrees C for 15 weeks and at 10 degrees C for ?1 year and correlated with
      temperatures recorded in Wales. Development was slowed/arrested at ?10 degrees C
      which reflects habitat conditions for >6 months/year. There was wide variation in
      growth at constant temperature (body size differing by >10 times) potentially
      attributable in part to genotype-specific host-parasite interactions. Parasite
      density had no effect on size but host sex did: worms in males were 1.8 times
      larger than in females. Minimum time to patency was 51 days at 25 degrees C and
      73 days at 20 degrees C although some infections were still not patent at both
      temperatures by 105 days p.i. In Wales, fastest developing infections may mature
      within one summer (about 12 weeks), possibly accelerated by movements of hosts
      into warmer surface waters. Otherwise, development slows/stops in October-April,
      delaying patency to about 1 year p.i., while wide variation in developmental
      rates may impose delays of 2 years in some primary infections and even longer in
      secondary infections.

PMID- 21733262
TI  - Site selection of Acanthochondria cornuta (Copepoda: Chondracanthidae) in
      Platichthys flesus (Teleostei: Pleuronectidae).
AB  - Acanthochondria cornuta (Copepoda: Chondracanthidae) (N=4841; prevalence: 80.0%;
      mean+/-s.d. [range] intensity: 28.8+/-24.0 [1-110] parasites) infected the
      branchial chambers of the European flounder, Platichthys flesus (L.), (N=210)
      according to an established spatial pattern. This was independent of host size.
      Higher intensities resulted, most frequently, in higher numbers of infection
      sites, probably due to increased intraspecific competition. Preferential
      infection of the ocular side was supported by the recorded abundance data and
      reflected, probably, the fish's bottom-dwelling behaviour. As the parasite
      develops from one stage into another, it seems to migrate towards different
      sites: the copepodites and pre-adult females occurred, mainly, in the
      holobranchs; the adults preferred the internal wall (non-gravid/post-gravid
      females; adult males) or the pseudobranchs (gravid females). The ventilating
      water current along with the blood supply are suggested as 2 major factors in
      determining parasite spatial distribution within the chamber. Parasite crowding
      in a restricted and narrow space of the posterior region of the internal wall was
      recorded frequently and resembled that previously reported for the plaice.
      Differences to other host-parasite systems previously studied should relate with
      the anatomy of the respiratory apparatus. Bigamous females are reported for the
      first time.

PMID- 21733263
TI  - Determinants of anti-hepatitis A antibody seroprevalence in 2- to 19-year-olds in
      the USA using NHANES 2007-2008.
AB  - The aim of the study was to describe the epidemiology and determinants of anti
      hepatitis A seroprevalence in 2- to 19-year-olds in the USA for 2007-2008. This
      study was conducted in a sample of 2621 individuals aged 2-19 years in the USA
      using data from National Health and Nutrition Examination Survey (NHANES) 2007
      2008. The overall seroprevalence of anti- hepatitis A virus (HAV) in this
      population was 39% (95% confidence interval 32.6-45.3). HAV seroprevalence was
      higher in Mexican Americans than other ethnic groups, in younger persons, and in
      those who reported previous vaccination compared to those who did not. We
      concluded that anti-hepatitis A seroprevalence rates are increasing in younger
      individuals in the USA, indicating a shift of seroprevalence over time due to
      vaccination status. Findings are consistent with a persistent influx of infection
      through international travel and migration and highlight the need to discern
      hepatitis A infection from vaccination status when assessing the effectiveness of
      vaccination using seroprevalence data.

PMID- 21733264
TI  - The risk of airborne influenza transmission in passenger cars.
AB  - Travel in passenger cars is a ubiquitous aspect of the daily activities of many
      people. During the 2009 influenza A(H1N1) pandemic a case of probable
      transmission during car travel was reported in Australia, to which spread via the
      airborne route may have contributed. However, there are no data to indicate the
      likely risks of such events, and how they may vary and be mitigated. To address
      this knowledge gap, we estimated the risk of airborne influenza transmission in
      two cars (1989 model and 2005 model) by employing ventilation measurements and a
      variation of the Wells-Riley model. Results suggested that infection risk can be
      reduced by not recirculating air; however, estimated risk ranged from 59% to
      99.9% for a 90-min trip when air was recirculated in the newer vehicle. These
      results have implications for interrupting in-car transmission of other illnesses
      spread by the airborne route.

PMID- 21733265
TI  - African horse sickness in The Gambia: circulation of a live-attenuated vaccine
      derived strain.
AB  - African horse sickness virus serotype 9 (AHSV-9) has been known for some time to
      be circulating amongst equids in West Africa without causing any clinical disease
      in indigenous horse populations. Whether this is due to local breeds of horses
      being resistant to disease or whether the AHSV-9 strains circulating are
      avirulent is currently unknown. This study shows that the majority (96%) of
      horses and donkeys sampled across The Gambia were seropositive for AHS, despite
      most being unvaccinated and having no previous history of showing clinical signs
      of AHS. Most young horses (<3 years) were seropositive with neutralizing
      antibodies specific to AHSV-9. Eight young equids (<3 years) were positive for
      AHSV-9 by serotype-specific RT-PCR and live AHSV-9 was isolated from two of these
      horses. Sequence analysis revealed the presence of an AHSV-9 strain showing 100%
      identity to Seg-2 of the AHSV-9 reference strain, indicating that the virus
      circulating in The Gambia was highly likely to have been derived from a live
      attenuated AHSV-9 vaccine strain.

PMID- 21733266
TI  - First reported foodborne outbreak associated with microsporidia, Sweden, October
      2009.
AB  - Microsporidia are spore-forming intracellular parasites that infrequently cause
      disease in immunocompetent persons. This study describes the first report of a
      foodborne microsporidiosis outbreak which affected persons visiting a hotel in
      Sweden. Enterocytozoon bieneusi was identified in stool samples from 7/11 case
      patients, all six sequenced samples were genotype C. To confirm that this was not
      a chance finding, 19 stool samples submitted by healthy persons from a comparable
      group who did not visit the hotel on that day were tested; all were negative for
      microsporidia. A retrospective cohort study identified 135 case-patients (attack
      rate 30%). The median incubation period was 9 days. Consumption of cheese
      sandwiches [relative risk (RR) 4.1, 95% confidence interval (CI) 1.4-12.2] and
      salad (RR 2.1, 95% CI 1.1-4) were associated with illness. Both items contained
      pre-washed, ready-to-eat cucumber slices. Microsporidia may be an under-reported
      cause of gastrointestinal outbreaks; we recommend that microsporidia be explored
      as potential causative agents in food- and waterborne outbreaks, especially when
      no other organisms are identified.

PMID- 21733267
TI  - Body composition and appetite: fat-free mass (but not fat mass or BMI) is
      positively associated with self-determined meal size and daily energy intake in
      humans.
AB  - The idea of body weight regulation implies that a biological mechanism exerts
      control over energy expenditure and food intake. This is a central tenet of
      energy homeostasis. However, the source and identity of the controlling mechanism
      have not been identified, although it is often presumed to be some long-acting
      signal related to body fat, such as leptin. Using a comprehensive experimental
      platform, we have investigated the relationship between biological and
      behavioural variables in two separate studies over a 12-week intervention period
      in obese adults (total n 92). All variables have been measured objectively and
      with a similar degree of scientific control and precision, including
      anthropometric factors, body composition, RMR and accumulative energy consumed at
      individual meals across the whole day. Results showed that meal size and daily
      energy intake (EI) were significantly correlated with fat-free mass (FFM, P
      values < 0.02-0.05) but not with fat mass (FM) or BMI (P values 0.11-0.45) (study
      1, n 58). In study 2 (n 34), FFM (but not FM or BMI) predicted meal size and
      daily EI under two distinct dietary conditions (high-fat and low-fat). These data
      appear to indicate that, under these circumstances, some signal associated with
      lean mass (but not FM) exerts a determining effect over self-selected food
      consumption. This signal may be postulated to interact with a separate class of
      signals generated by FM. This finding may have implications for investigations of
      the molecular control of food intake and body weight and for the management of
      obesity.

PMID- 21733268
TI  - A school-based obesity control programme: Project Energize. Two-year outcomes.
AB  - Through-school nutrition and physical activity interventions are designed to help
      reduce excess weight gain and risk of chronic disease. From 2004 to 2006, Project
      Energize was delivered in the Waikato Region of New Zealand as a longitudinal
      randomised controlled study of 124 schools (year 1-6), stratified by rurality and
      social deprivation, and randomly assigned to intervention or control. Children
      (686 boys and 662 girls) aged 5 (1926) and 10 (1426) years (692 interventions and
      660 controls) had height, weight, body fat (by bioimpedance) and resting blood
      pressure (BP) measured at baseline and 2 years later. Each intervention school
      was assigned an 'Energizer'; a trained physical activity and nutrition change
      agent, who worked with the school to achieve goals based on healthier eating and
      quality physical activity. After adjustment for baseline measures, rurality and
      social deprivation, the intervention was associated with a reduced accumulation
      of body fat in younger children and a reduced rate of rise in systolic BP in
      older children. There was some evidence that the pattern of change within an age
      group varied with rurality, ethnicity and sex. We conclude that the introduction
      of an 'Energizer led' through-school programme may be associated with health
      benefits over 2 years, but the trajectory of this change needs to be measured
      over a longer period. Attention should also be paid to the differing response by
      ethnicity, sex, age group and the effect of rurality and social deprivation.

PMID- 21733269
TI  - Mapping the increasing risk of human alveolar echinococcosis in Limburg, The
      Netherlands.
AB  - The parasite Echinococcus multilocularis was first detected in The Netherlands in
      1996 and repeated studies have shown that the parasite subsequently spread in the
      local population of foxes in the province of Limburg. It was not possible to
      quantify the human risk of alveolar echinococcosis because no relationship
      between the amount of parasite eggs in the environment and the probability of
      infection in humans was known. Here, we used the spread of the parasite in The
      Netherlands as a predictor, together with recently published historical records
      of the epidemiology of alveolar echinococcosis in Switzerland, to achieve a
      relative quantification of the risk. Based on these analyses, the human risk in
      Limburg was simulated and up to three human cases are predicted by 2018. We
      conclude that the epidemiology of alveolar echinococcosis in The Netherlands
      might have changed from a period of negligible risk in the past to a period of
      increasing risk in the forthcoming years.

PMID- 21733270
TI  - An evaluation of dog rabies control in Limpopo province (South Africa).
AB  - Rabies is a prevalent and re-emerging disease in South Africa particularly in
      rural areas with high human densities. Outbreaks are frequently reported in the
      north and eastern parts of this country, probably an indication of inadequacy in
      the control of the disease. Following the 2005/2006 outbreak in Limpopo, we
      undertook an analysis of case surveillance data and genetically characterized 18
      rabies viruses, all recovered from domestic dogs. Although rabies prevalence
      gradually declined annually from 2007, dog rabies still remains a public and
      veterinary health hazard in this region. Sylvatic rabies cycles are maintained by
      the black-backed jackal species in specific ecological conditions in the
      northwest of the province (Waterberg area), unlike in the north and east (Vhembe
      and Mopani districts, respectively), where spillover of infection between dogs
      and jackals is likely to predominate. Genetic analysis demonstrated that the
      rabies virus strain currently circulating within dog populations in Limpopo
      province is the same variant responsible for the 2005/2006 rabies outbreak.
      However, residual foci probably exist hence the observed sporadic outbreaks.
      These data further underline the value of continuous and sustainable dog
      immunization in controlling rabies.

PMID- 21733271
TI  - Eliciting expert opinion on the effectiveness and practicality of interventions
      in the farm and rural environment to reduce human exposure to Escherichia coli
      O157.
AB  - Few hard data are available on emergent diseases. However, the need to mitigate
      and manage emergent diseases has prompted the use of various expert consultation
      and opinion elicitation methods. We adapted best-worst scaling (BWS) to elicit
      experts' assessment of the relative practicality and effectiveness of measures to
      reduce human exposure to E. coli O157. Cattle vaccination was considered the most
      effective and hand-washing was considered the most practical measure. BWS proved
      a powerful tool for expert elicitation as it breaks down a cognitively burdensome
      process into simple, repeated, tasks. In addition, statistical analysis of the
      resulting data provides a scaled set of scores for the measures, rather than just
      a ranking. The use of two criteria (practicality and effectiveness) within the
      BWS process allows the identification of subsets of measures judged as
      potentially performing well on both criteria, and conversely those judged to be
      neither effective nor practical.

PMID- 21733272
TI  - Transmission dynamics of primary pneumonic plague in the USA.
AB  - Plague is thought to have killed millions during three catastrophic pandemics.
      Primary pneumonic plague, the most severe form of the disease, is transmissible
      from person-to-person and has the potential for propagating epidemics. Efforts to
      quantify its transmission potential have relied on published data from large
      outbreaks, an approach that artificially inflates the basic reproductive number
      (R(0)) and skews the distribution of individual infectiousness. Using data for
      all primary pneumonic plague cases reported in the USA from 1900 to 2009, we
      determined that the majority of cases will fail to transmit, even in the absence
      of antimicrobial treatment or prophylaxis. Nevertheless, potential for sustained
      outbreaks still exists due to superspreading events. These findings challenge
      current concepts regarding primary pneumonic plague transmission.

PMID- 21733273
TI  - Emergence of metallo-beta-lactamase IMP-14 and VIM-2 in Pseudomonas aeruginosa
      clinical isolates from a tertiary-level hospital in Thailand.
AB  - Seventy-five clinical isolates of Pseudomonas aeruginosa collected in a tertiary
      teaching hospital in Thailand were investigated for susceptibility to
      antimicrobials including imipenem. Metallo-beta-lactamase (MBL) enzymes were
      detected by E-test MBL assay and PCR; class 1 integron genes were also detected
      by PCR. Strains positive for bla(IMP) and bla(VIM) genes were further
      characterized by DNA sequencing and examined for clonality by pulsed-field gel
      electrophoresis. High rates of resistance to anti-pseudomonal agents were found.
      MBL enzymes were found in 13 (17.3%) strains and 24 (32%) carried class 1
      integron genes. Twelve of the latter strains harboured the bla(IMP-14) gene and
      one strain the bla(VIM-2) gene. All of the IMP-14 strains were identical or
      closely related suggesting clonal dissemination of these genes.

PMID- 21733274
TI  - Molecular typing of adenovirus circulating in a Colombian paediatric population
      with acute respiratory infection.
AB  - Human adenoviruses (HAdV) cause a broad spectrum of diseases including acute
      respiratory infection (ARI), and are responsible for 5% of cases requiring
      hospitalization in children aged <5 years in Colombia; however, little is known
      about the circulating types, partly due to the lack of reliable typing tests. In
      order to evaluate a VA gene PCR-sequencing approach for identification of HAdV
      circulating types in a Colombian population, 52 nasopharyngeal aspirates/swabs
      from children with ARI were processed. After a BLAST analysis, matches with
      species B (41/48, 85.42%), C (6/48, 12.5%), and D (1/48, 2.08%) were found; and
      at the type level, type 3 (22/48, 45.83%) was the most frequent. This initial
      effort to expand our knowledge about the molecular epidemiology of HAdV
      circulating in Bogota, Colombia, showed that HAdV-B was the predominant
      circulating species in the study period and reports, for the first time in
      Colombia, the presence of HAdV-D in a respiratory sample.

PMID- 21733275
TI  - Seroprevalence of toxocariasis in hypereosinophilic individuals in Ahwaz, south
      western Iran.
AB  - Eosinophilia in human peripheral blood is caused by different agents, including
      toxocariasis. The present study aimed to evaluate the prevalence of toxocariasis
      in hypereosinophilic individuals in the city of Ahwaz, located in south-western
      Iran, using enzyme-linked immunosorbent assay and Western blot techniques. Serum
      samples were examined from 100 individuals with peripheral blood eosinophilia and
      also from another 100 individuals without eosinophilia as the control group. In
      hypereosinophilic individuals seroprevalence antibodies against Toxocara were
      found in 19 (19%), of whom 12 (63.15%) were female and 7 (36.85%) were male.
      Positive sera were subsequently confirmed by Western blot. All of the observed
      bands ranged from 24 to 100 kDa. Antibodies against Toxocara were found in 1% of
      the control group, but were not confirmed by Western blot. The results showed
      significant differences between the frequency of infection within age and gender
      (P < 0.05); the highest prevalence of infection was observed in adults.
      Differences between the hypereosinophilic and healthy individuals, in terms of
      Toxocara infection frequency, also proved significant (P < 0.05).The present
      study thus confirmed the significant prevalence of toxocariasis as a hygienic
      problem among hypereosinophilic individuals in this area. It is, therefore,
      necessary to examine these individuals for toxocariasis.

PMID- 21733276
TI  - 'A good shepherd, but with obstructive sleep apnoea syndrome': traditional
      uvulectomy case series and literature review.
AB  - BACKGROUND: In the West, removal of the uvula is predominantly undertaken as part
      of palatal surgery, in cases of obstructive sleep apnoea. In the developing
      world, such as the Middle East and Africa, uvulectomy is a more common practice.
      The uvula is removed for curative or preventive purposes, or as part of ritual
      practice. Due to immigration from developing to developed world countries, and to
      Western doctors working abroad, such doctors are increasingly being confronted
      with unfamiliar traditional healing practices, within a medical context. METHODS:
      The Medline and Embase online databases were systematically searched for
      literature on traditional uvulectomy. We present a review of this literature. We
      also present the first report, to our best knowledge, of obstructive sleep apnoea
      as a late complication of traditional uvulectomy. DISCUSSION: Traditional
      uvulectomy may be complicated by post-operative haemorrhage and local infections,
      among many other problems. We report cases of obstructive sleep apnoea and
      snoring caused by palatal stenosis resulting from traditional uvulectomy during
      childhood.

PMID- 21733277
TI  - Nasal extranodal natural killer T cell lymphoma: an atypical presentation.
AB  - OBJECTIVE: We report two cases of nasal natural killer T cell lymphoma which
      presented atypically following surgical intervention. CASE REPORT: Two patients
      with a previous history of endoscopic nasal surgery presented with progressive
      facial swelling and necrosis. The histology of several nasal biopsies was
      suggestive of acute, necrotising inflammation. Considering these patients'
      midline destruction of the nose and face, and their inconclusive biopsies,
      immunohistochemical studies were undertaken, enabling the diagnosis of peripheral
      natural killer T cell lymphoma. CONCLUSION: Natural killer T cell lymphoma of the
      sinonasal tract is an important differential diagnosis of destructive lesions of
      the nose and midface. The definitive diagnosis is often delayed. Hence, this
      tumour should be considered in patients with atypical presentations of acute
      inflammation following surgical intervention; such patients should be thoroughly
      investigated. Early immunohistochemical investigation is needed to enable prompt
      diagnosis in suspicious cases.

PMID- 21733278
TI  - Do Latino and non-Latino grocery stores differ in the availability and
      affordability of healthy food items in a low-income, metropolitan region?
AB  - OBJECTIVE: To compare non-ethnically based supermarkets and Latino grocery stores
      (tiendas) in a lower-income region with regard to the availability, quality and
      cost of several healthy v. unhealthy food items. DESIGN: A cross-sectional study
      conducted by three independent observers to audit twenty-five grocery stores
      identified as the main source of groceries for 80 % of Latino families enrolled
      in a childhood obesity study. Stores were classified as supermarkets and tiendas
      on the basis of key characteristics. SETTING: South San Diego County. SUBJECTS:
      Ten tiendas and fifteen supermarkets. RESULTS: Tiendas were smaller than
      supermarkets (five v. twelve aisles, P = 0.003). Availability of fresh produce
      did not differ by store type; quality differed for one fruit item. Price per unit
      (pound or piece) was lower in tiendas for most fresh produce. The cost of meeting
      the US Department of Agriculture's recommended weekly servings of produce based
      on an 8368 kJ (2000 kcal)/d diet was $US 3.00 lower in tiendas compared with
      supermarkets (P < 0.001). The cost of 1 gallon of skimmed milk was significantly
      higher in tiendas ($US 3.29 v. $US 2.69; P = 0.005) and lean (7 % fat) ground
      beef was available in only one tienda (10 %) compared with ten (67 %)
      supermarkets (P = 0.01). CONCLUSIONS: Barriers remain in the ability to purchase
      healthier dairy and meat options in tiendas; the same is not true for produce.
      These results highlight the potential that tiendas have in improving access to
      quality, fresh produce within lower-income communities. However, efforts are
      needed to increase the access and affordability of healthy dairy and meat
      products.

PMID- 21733279
TI  - Dietary habits and inadequate control of blood pressure in hypertensive adults
      assisted by a Brazilian Family Doctor Program.
AB  - OBJECTIVE: To estimate dietary habits and other factors associated with
      inadequate blood pressure (BP) control in hypertensive patients adherent to
      antihypertensive drug treatment assisted by a Brazilian Family Doctor Program
      (FDP). DESIGN: A cross-sectional study. SETTING: FDP units, Niteroi, Rio de
      Janeiro, Brazil. SUBJECTS: We included data from both male and female
      participants aged >=20 years. Participants completed a standardized questionnaire
      containing questions related to demographics, socio-economic factors,
      comorbidities and lifestyle, as well as a validated FFQ and eleven additional
      qualitative questions to investigate dietary habits. Food items were divided into
      sixteen groups. Medical consultations were performed, BP measurements were taken,
      blood and urine samples were assessed and anthropometric and nutritional status
      was evaluated. RESULTS: Individuals with inadequate BP control presented higher
      BMI values (prevalence ratio (PR) = 1.027, 95% CI 1.009, 1.045) and also consumed
      more meat (PR = 1.091, 95% CI 1.022, 1.165), which are potentially modifiable
      variables. Higher levels of serum creatinine (PR = 1.894, 95% CI 1.241, 2.892)
      were also associated with inadequate BP control, as were skin colour (white).
      After inclusion of the Na excretion index, which is an indirect measure of salt
      intake, a slight decrease was observed in the PR for meat, which resulted in loss
      of statistical significance. CONCLUSIONS: The results indicate that salt
      consumption, skin colour, BMI and serum creatinine are associated with inadequate
      BP control.

PMID- 21733280
TI  - Predictors of nutrition label viewing during food purchase decision making: an
      eye tracking investigation.
AB  - OBJECTIVE: Nutrition label use could help consumers eat healthfully. Despite
      consumers reporting label use, diets are not very healthful and obesity rates
      continue to rise. The present study investigated whether self-reported label use
      matches objectively measured label viewing by monitoring the gaze of individuals
      viewing labels. DESIGN: The present study monitored adults viewing sixty-four
      food items on a computer equipped with an eye-tracking camera as they made
      simulated food purchasing decisions. ANOVA and t tests were used to compare label
      viewing across various subgroups (e.g. normal weight v. overweight v. obese;
      married v. unmarried) and also across various types of foods (e.g. snacks v.
      fruits and vegetables). SETTING: Participants came to the University of
      Minnesota's Epidemiology Clinical Research Center in spring 2010. SUBJECTS: The
      203 participants were >=18 years old and capable of reading English words on a
      computer 76 cm (30 in) away. RESULTS: Participants looked longer at labels for
      'meal' items like pizza, soup and yoghurt compared with fruits and vegetables,
      snack items like crackers and nuts, and dessert items like ice cream and cookies.
      Participants spent longer looking at labels for foods they decided to purchase
      compared with foods they decided not to purchase. There were few between-group
      differences in nutrition label viewing across sex, race, age, BMI, marital
      status, income or educational attainment. CONCLUSIONS: Nutrition label viewing is
      related to food purchasing, and labels are viewed more when a food's
      healthfulness is ambiguous. Objectively measuring nutrition label viewing
      provides new insight into label use by various sociodemographic groups.

PMID- 21733281
TI  - What is the real cost of our food? Implications for the environment, society and
      public health nutrition.
AB  - The current, globalised food system supplies 'cheap' food to a large proportion
      of the world's population, but with significant social, environmental and health
      costs that are poorly understood. The present paper examines the nature and
      extent of these costs for both rural and urban communities, by illustrating the
      financial pressures on food producers and manufacturers to produce cheap food,
      the disconnection people experience with how and where their food is produced,
      and the rise in obesity levels that plague the globe. The paper then proposes
      that community food systems may play an important role in mitigating the adverse
      environmental, economic and social effects of the dominant food system, by the
      use of more sustainable food production methods, the development of local
      economies and enabling closer connections between farmers and consumers. There
      are many opportunities for public health nutritionists to contribute to the local
      food system literature to ascertain whether these systems improve inequities,
      provide better access to healthy food and help stem the tide of rising global
      obesity levels. Public health nutritionists can play a key role in supporting
      people to become food citizens and to advocate for democratic and sustainable
      food systems.

PMID- 21733282
TI  - Rapid-acting antidepressant strategies: mechanisms of action.
AB  - Current antidepressants are ineffective in many depressed patients. Thus there is
      an urgent need to develop treatment strategies which have significantly faster
      response, can be sustained and have minimal side-effects. This paper reviews
      clinical data, potential biomarkers, mechanisms of action and future research
      directions for two proven strategies that produce marked improvement in severe
      depressive symptoms within 48 h, ketamine and sleep deprivation therapy (SDT).
      These treatments provide unequivocal evidence that the depressive process can be
      rapidly reversed in a subgroup of patients. Seventeen ketamine studies in over
      150 patients showed a rapid response. Low-dose intravenous ketamine produced mild
      psychotomimetic effects but response has not been effectively sustained. SDT has
      been investigated in over 60 studies with a 40-60% response rate within 48 h.
      Although SDT is often used in Europe to initiate a rapid response, it is less
      utilized within the USA, in part, because it has a short duration when
      administered alone. We review data concerning chronotherapeutic strategies of
      bright-light therapy (BLT) and sleep-phase advance (SPA) which successfully
      sustain the antidepressant efficacy of SDT. Evidence is further discussed that a
      significant group of mood disorders have abnormal circadian rhythms which are
      known to be controlled by clock genes. It is hypothesized that chronotherapeutic
      manipulations can reset clock genes and thus, abnormalities in circadian rhythms.
      Further findings are reviewed that ketamine, in addition to its role as an NMDA
      antagonist, can also alter circadian rhythms. Thus, ketamine may share a critical
      mechanism with SDT.

PMID- 21733283
TI  - D-serine adjuvant treatment alleviates behavioural and motor symptoms in
      Parkinson's disease.
AB  - Parkinson's disease (PD) manifestations include motor symptoms and behavioural
      deficits that resemble schizophrenia negative symptoms. The N-methyl-D-aspartate
      subtype of glutamate receptor (NMDAR) represents a novel pharmacological target
      in PD. D-serine (DSR) allosterically modulates in-vivo NMDAR-mediated
      neurotransmission and has been shown to improve negative and antipsychotic drug
      induced parkinsonian symptoms in schizophrenia patients. This pilot study
      assessed DSR effects in ten PD patients who completed a 6-wk double-blind,
      placebo-controlled, crossover adjuvant treatment trial with 30 mg/kg.d DSR.
      Primary outcome analyses consisted of separate repeated-measures multivariate
      analyses of variance for Unified Parkinson's Disease Rating Scale (UPDRS),
      Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), Abnormal Involuntary
      Movement Scale (AIMS), and Positive and Negative Syndrome Scale (PANSS) scores.
      DSR treatment was well tolerated and resulted in increased DSR serum levels
      (p=0.001) and significantly reduced UPDRS (p=0.02), SAS (p=0.009) and PANSS
      (0.05) total scores. These preliminary findings suggest that DSR treatment may be
      beneficial in PD. Larger-sized studies with optimized DSR dosages are warranted.

PMID- 21733284
TI  - The suppression of appetite and food consumption by methylphenidate: the
      moderating effects of gender and weight status in healthy adults.
AB  - Females typically show greater behavioural responses to stimulant drugs than
      males, including loss of appetite; as seen, for example, in those who use
      methylphenidate (MP) therapeutically for treatment of attention deficit
      hyperactivity disorder (ADHD). This is a relevant issue because of the strong
      link between ADHD and obesity. In a sample (n=132) of normal-weight (BMI <25) and
      obese (BMI >30) men and women we assessed appetite, cravings, and snack-food
      intake in response to MP (0.5 mg/kg) and placebo. Results indicated a significant
      three-way interaction for the three dependent variables--food-related responding
      diminishing in all groups from placebo to MP, except in obese males who showed no
      decreases to the MP challenge. These data show for the first time the existence
      of gender differences in the appetite response to MP, and are relevant for
      finding a dopamine pathway to new weight-loss medications, which would be
      utilized differently in males than in females.

PMID- 21733285
TI  - Importance of inter-hemispheric prefrontal connection in the effects of non
      competitive NMDA receptor antagonists.
AB  - Previous studies have shown that systemic, but not unilateral intra-prefrontal
      cortex administration of non-competitive NMDA antagonists, increased prefrontal
      activity, the cortical efflux of serotonin, and induced stereotypies. In this
      work we used in-vivo microdialysis and immunohistochemistry to test the
      hypothesis as to whether MK-801 and ketamine need to act on both prefrontal
      cortices to reproduce these neurochemical and behavioural changes. Dialysis
      probes were implanted in the medial prefrontal cortex, and extracellular
      serotonin as well as behavioural stereotypies was measured after systemic
      administration of MK-801 and ketamine (1 mg/kg and 25 mg/kg, respectively), and
      unilateral and bilateral perfusion of both drugs (300 MUm and 3 mm,
      respectively). Additionally, the prefrontal (glutamatergic) level of activity was
      measured using c-Fos immunohistochemistry. Systemic and bilateral (but not
      unilateral) prefrontal administration of MK-801 and ketamine increased serotonin
      efflux whereas only systemic administration of both drugs produced
      hyperlocomotion and stereotypies. The unilateral perfusion of 1 MUm tetrodotoxin
      in the medial prefrontal cortex reduced increases of serotonin in both
      hemispheres, the expression of c-Fos in the contralateral side, and stereotypy
      scores after systemic NMDA antagonists. Our results support the hypothesis that a
      bilateral impairment of cortical inhibition in the medial prefrontal cortex is
      needed for non-competitive NMDA antagonists to induce the state of pyramidal cell
      hyperactivity and concurrent efflux of serotonin. Furthermore, hyperlocomotion
      and stereotypies produced by MK-801 and ketamine do not appear to result from
      changes in the activity of prefrontal cortex although this structure exerts some
      control over these behaviours.

PMID- 21733286
TI  - First-episode psychosis is characterized by failure of deactivation but not by
      hypo- or hyperfrontality.
AB  - BACKGROUND: It is not known whether first-episode psychosis is characterized by
      the same prefrontal cortex functional imaging abnormalities as chronic
      schizophrenia. METHOD: Thirty patients with a first episode of non-affective
      functional psychosis and 28 healthy controls underwent functional magnetic
      resonance imaging (fMRI) during performance of the n-back working memory task.
      Voxel-based analyses of brain activations and deactivations were carried out and
      compared between groups. The connectivity of regions of significant difference
      between the patients and controls was also examined. RESULTS: The first-episode
      patients did not show significant prefrontal hypo- or hyperactivation compared to
      controls. However, they showed failure of deactivation in the medial frontal
      cortex. This area showed high levels of connectivity with the posterior cingulate
      gyrus/precuneus and parts of the parietal cortex bilaterally. Failure of
      deactivation was significantly greater in first-episode patients who had or went
      on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and
      in those who met RDC criteria for schizophrenia compared to those who did not.
      CONCLUSIONS: First-episode psychosis is not characterized by hypo- or
      hyperfrontality but instead by a failure of deactivation in the medial frontal
      cortex. The location and connectivity of this area suggest that it is part of the
      default mode network. The failure of deactivation seems to be particularly marked
      in first-episode patients who have, or progress to, schizophrenia.

PMID- 21733287
TI  - Abnormal prefrontal activity subserving attentional control of emotion in
      remitted depressed patients during a working memory task with emotional
      distracters.
AB  - BACKGROUND: Patients with major depressive disorder (MDD) show deficits in
      processing of facial emotions that persist beyond recovery and cessation of
      treatment. Abnormalities in neural areas supporting attentional control and
      emotion processing in remitted depressed (rMDD) patients suggests that there may
      be enduring, trait-like abnormalities in key neural circuits at the interface of
      cognition and emotion, but this issue has not been studied systematically.
      METHOD: Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years;
      mean duration of illness 34 months) and 20 age- and gender-matched healthy
      controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK)
      task, a working memory task with emotional distracter stimuli. We used blood
      oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to
      measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal
      cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using
      a region of interest (ROI) approach in SPM2. RESULTS: rMDD patients exhibited
      significantly greater activity relative to HC in the left DLPFC [Brodmann area
      (BA) 9/46] in response to negative emotional distracters during high working
      memory load. By contrast, rMDD patients exhibited significantly lower activity in
      the right DLPFC and left VLPFC compared to HC in response to positive emotional
      distracters during high working memory load. These effects occurred during
      accurate task performance. CONCLUSIONS: Remitted depressed patients may continue
      to exhibit attentional biases toward negative emotional information, reflected by
      greater recruitment of prefrontal regions implicated in attentional control in
      the context of negative emotional information.

PMID- 21733288
TI  - Poor school performance in offspring of patients with schizophrenia: what are the
      mechanisms?
AB  - BACKGROUND: Offspring of patients with schizophrenia exhibit poorer school
      performance compared with offspring of non-schizophrenic parents. We aimed to
      elucidate the mechanisms behind this association. METHOD: We linked longitudinal
      national population registers in Sweden and compared school performance among
      offspring of schizophrenic parents with offspring of non-schizophrenic parents (1
      439 215 individuals with final grades from compulsory school 1988-2006). To
      investigate the mechanisms, we studied offspring of schizophrenic patients and
      controls within the same extended families. We investigated genetic effects by
      stratifying analyses of parent-child associations according to genetic
      relatedness (half-cousins, full cousins and half-siblings). Environmental effects
      were investigated by comparing school performance of offspring of schizophrenic
      fathers and of schizophrenic mothers, respectively, and by stratifying the
      analyses according to environmental relatedness while controlling genetic
      relatedness (paternal and maternal half-cousins, paternal and maternal half
      siblings). RESULTS: Offspring of parents with schizophrenia had poorer overall
      school performance than unrelated offspring of non-schizophrenic parents (-0.31
      s.d.). Variability in genetic relatedness greatly moderated the strength of the
      within-family association (beta=-0.23 within exposure-discordant half-cousins,
      beta=-0.13 within exposure-discordant full cousins, beta=0.04 within exposure
      discordant half-siblings), while no evidence was found that the environment
      affected offspring school performance. CONCLUSIONS: Genetic factors account for
      poorer school performance in children of parents with schizophrenia. This
      supports that cognitive deficits found in individuals with schizophrenia and
      their relatives might be genetically inherited. Early detection of prodromal
      signs and impaired functioning of offspring of patients with schizophrenia could
      lead to earlier and better tailored interventions.

PMID- 21733289
TI  - Subjective experience and meaning of psychoses: the German Subjective Sense in
      Psychosis Questionnaire (SUSE).
AB  - BACKGROUND: Clinical research on subjective determinants of recovery and health
      has increased, but no instrument has been developed to assess the subjective
      experience and meaning of psychoses. We have therefore constructed and validated
      the Subjective Sense in Psychosis Questionnaire (SUSE) to measure sense making in
      psychotic disorders. METHOD: SUSE was based on an item pool generated by
      professionals and patients. For pre-testing, 90 psychosis patients completed the
      instrument. Psychometric properties were assessed using methods of classical test
      theory. In the main study, SUSE was administered to a representative sample of
      400 patients. Factor structure, reliability and validity were assessed and
      confirmatory factor analyses (CFAs) were used for testing subscale coherence and
      adequacy of the hypothesized factor structure. Response effects due to clinical
      settings were tested using multilevel analyses. RESULTS: The final version of
      SUSE comprises 34 items measuring distinct aspects of the experience and meaning
      of psychoses in a consistent overall model with six coherent subscales
      representing positive and negative meanings throughout the course of psychotic
      disorders. Multilevel analyses indicate independence from clinical context
      effects. Patients relating psychotic experiences to life events assessed their
      symptoms and prospects more positively. 76% of patients assumed a relationship
      between their biography and the emergence of psychosis, 42% reported positive
      experience of symptoms and 74% ascribed positive consequences to their psychosis.
      CONCLUSIONS: SUSE features good psychometric qualities and offers an empirical
      acquisition to subjective assessment of psychosis. The results highlight the
      significance of subjective meaning making in psychoses and support a more
      biographical and in-depth psychological orientation for treatment.

PMID- 21733290
TI  - Self-monitoring as a familial vulnerability marker for psychosis: an analysis of
      patients, unaffected siblings and healthy controls.
AB  - BACKGROUND: Alterations in self-monitoring have been reported in patients with
      psychotic disorders, but it remains unclear to what degree they represent true
      indicators of familial vulnerability for psychosis. METHOD: An error-correction
      action-monitoring task was used to examine self-monitoring in 42 patients with
      schizophrenia, 32 of their unaffected siblings and 41 healthy controls. RESULTS:
      Significant between-group differences in self-monitoring accuracy were found
      (chi2=29.3, p<0.0001), patients performing worst and unaffected siblings
      performing at an intermediate level compared to controls (all between-group
      differences p<0.05). In the combined group of healthy controls and unaffected
      siblings, detection accuracy was associated with positive schizotypy as measured
      by the Structured Interview for Schizotypy - Revised (SIS-R) (beta=-0.16,
      s.e.=0.07, p=0.026), but not with negative schizotypy (beta=-0.05, s.e.=0.12,
      p=0.694). In patients, psychotic symptoms were not robustly associated with
      detection accuracy (beta=-0.01, s.e.=0.01, p=0.094), although stratified analysis
      revealed suggestive evidence for association in patients not currently using
      antipsychotic medication (beta=-0.03, s.e.=0.01, p=0.052), whereas no association
      was found in patients on antipsychotic medication (beta=-0.01, s.e.=0.01,
      p=0.426). A similar pattern of associations was found for negative symptoms.
      CONCLUSIONS: Alterations in self-monitoring may be associated with familial risk
      and expression of psychosis. The association between psychotic symptoms and self
      monitoring in patients may be affected by antipsychotic medication, which may
      explain previous inconsistencies in the literature.

PMID- 21733291
TI  - Striatal function in relation to negative symptoms in schizophrenia.
AB  - BACKGROUND: Previous studies have suggested that motivational aspects of
      executive functioning, which may be disrupted in schizophrenia patients with
      negative symptoms, are mediated in part by the striatum. Negative symptoms have
      been linked to impaired recruitment of both the striatum and the dorsolateral
      prefrontal cortex (DLPFC). Here we tested the hypothesis that negative symptoms
      are associated primarily with striatal dysfunction, using functional magnetic
      resonance imaging (fMRI). METHOD: Working-memory load-dependent activation and
      gray matter volumes of the striatum and DLPFC were measured using a region-of
      interest (ROI) approach, in 147 schizophrenia patients and 160 healthy controls.
      In addition to testing for a linear relationships between striatal function and
      negative symptoms, we chose a second, categorical analytic strategy in which we
      compared three demographically and behaviorally matched subgroups: patients with
      a high burden of negative symptoms, patients with minimal negative symptoms, and
      healthy subjects. RESULTS: There were no differences in striatal response
      magnitudes between schizophrenia patients and healthy controls, but right DLPFC
      activity was higher in patients than in controls. Negative symptoms were
      inversely associated with striatal, but not DLPFC, activity. In addition,
      patients with a high burden of negative symptoms exhibited significantly lower
      bilateral striatal, but not DLPFC, activation than schizophrenia patients with
      minimal negative symptoms. Working memory performance, antipsychotic exposure and
      changes in gray matter volumes did not account for these differences.
      CONCLUSIONS: These data provide further evidence for a robust association between
      negative symptoms and diminished striatal activity. Future work will determine
      whether low striatal activity in schizophrenia patients could serve as a reliable
      biomarker for negative symptoms.

PMID- 21733292
TI  - Drug cue induced overshadowing: selective disruption of natural reward processing
      by cigarette cues amongst abstinent but not satiated smokers.
AB  - BACKGROUND: Addicts show both reward processing deficits and increased salience
      attribution to drug cues. However, no study to date has demonstrated that
      salience attribution to drug cues can directly modulate inferences of reward
      value to non-drug cues. Associative learning depends on salience: a more salient
      predictor of an outcome will 'overshadow' a less salient predictor of the same
      outcome. Similarly, blocking, a demonstration that learning depends on prediction
      error, can be influenced by the salience of the cues employed. METHOD: This study
      investigated whether salient drug cues might interact with neutral cues
      predicting financial reward in an associative learning task indexing blocking and
      overshadowing in satiated smokers (n=24), abstaining smokers (n=24) and non
      smoking controls (n=24). Attentional bias towards drug cues, craving and expired
      CO were also indexed. RESULTS: Abstaining smokers showed drug cue induced
      overshadowing, attributing higher reward value to drug cues than to neutral cues
      that were equally predictive of reward. Overshadowing was positively correlated
      with expired CO levels, which, in turn, were correlated with craving in
      abstainers. An automatic attentional bias towards cigarette cues was found in
      abstainers only. CONCLUSIONS: These findings provide the first evidence that drug
      cues interact with reward processing in a drug dependent population.

PMID- 21733293
TI  - Early development of Brycon orthotaenia (Pisces: Characidae).
AB  - Brycon orthotaenia is an important fish for commercial and sport fishing and may
      reach 7 kg in body weight; it is endangered in some regions of Brazil's Sao
      Francisco River Basin. Breeders were subjected to spawning induction to analyse
      the early development; oocytes and semen were obtained by manual extrusion and
      fertilization was carried out using the dry method. After fertilization, eggs
      were kept in incubators at 24 degrees C. Egg samples were collected every 10 min
      until hatching in order to monitor embryonic development and were analysed and
      photographed. Larvae samples were collected daily until the seventh day to
      analyse the larvae development; larvae were fixed in Bouin's fluid and subjected
      to routine histological and histochemical techniques for glycoprotein and glyco
      conjugated detection. Oocyte extrusion occurred 6 h after the second hormone dose
      at 26 degrees C. The recently extruded oocytes were spherical, dark green and non
      adhesive, with a diameter of 1479.67 +/- 53.18 and 3094.60 +/- 80.34 MUm after
      hydration. The blastopore closure occurred within 7 h 30 min of fertilization and
      the fertilization rate was 50.0 +/- 5.5 % at 24 degrees C. Embryonic development
      was completed within 21 h 30 min of fertilization. Complete yolk sac resorption
      and mouth opening occurred on the third day after hatching, at which time an
      adhesive organ with mucosubstances was observed. On the third day, an olfactory
      chamber with cilia and intense cannibalism amongst the larvae was observed. The
      complete differentiation of the digestive system occurred on the fifth day and
      the nervous and sensorial systems differentiation occurred on the sixth to
      seventh days.

PMID- 21733294
TI  - Nutraceutical value and safety of tomato fruits produced by mycorrhizal plants.
AB  - Tomato fruit has assumed the status of 'functional food' due to the association
      between its consumption and a reduced likelihood of certain types of cancers and
      CVD. The nutraceutical value of tomatoes can be affected by the cultivation
      conditions, e.g. the phytochemical content of the fruits may increase with the
      establishment of beneficial mycorrhizal symbioses in the plants. A
      multidisciplinary study was carried out to gain knowledge on the antioxidant,
      oestrogenic/anti-oestrogenic and genotoxic activity of tomato fruits produced by
      mycorrhizal plants. The present results showed that the symbiosis positively
      affected the growth and mineral nutrient content of tomato plants and enhanced
      the nutritional and nutraceutical value of tomato fruits through modifications of
      plant secondary metabolism, which led to increased levels of lycopene in fruits
      obtained from mycorrhizal plants, compared with controls. Moreover, such changes
      did not result in the production of mutagenic compounds, since tomato extracts
      induced no in vitro genotoxic effects. Fruit extracts, both hydrophilic and the
      lipophilic fractions, originating from mycorrhizal plants strongly inhibited 17
      beta-oestradiol-human oestrogen receptor binding, showing significantly higher
      anti-oestrogenic power compared with controls. The present study shows that
      beneficial plant symbionts, such as mycorrhizal fungi, can lead to the production
      of safe and high-quality food, which is an important societal issue strongly
      demanded by both consumers and producers.

PMID- 21733295
TI  - Adverse metabolic phenotype in low-birth-weight lambs and its modification by
      postnatal nutrition.
AB  - Both high and low maternal dietary intakes adversely affect fetal nutrient supply
      in adolescent sheep pregnancies. Aims were: (a) to assess the impact of prenatal
      nutrition on pregnancy outcome, offspring growth and offspring glucose metabolism
      and (b) to determine whether the offspring metabolic phenotype could then be
      altered by modifying postnatal nutrition. Dams carrying a single fetus were
      offered either an optimal control (C) intake to maintain adiposity throughout
      pregnancy, undernourished to maintain weight at conception but deplete maternal
      reserves (UN), or overnourished to promote rapid maternal growth and adiposity
      (ON). Placental weight and gestation length were reduced in ON dams and lamb
      birth weights were C>UN>ON (P < 0.001). All offspring were fed ad libitum from
      weaning to 6 months of age. ON offspring exhibited rapid catch-up growth and had
      increased fasting glucose and relative glucose intolerance compared with C
      offspring (P < 0.05). Irrespective of prenatal diet and sex, birth weight
      correlated negatively with these indices of glucose metabolism. From 7 to 12
      months offspring either had continued ad libitum diet (ADLIB; to induce an
      obesogenic state) or a decreased ration appropriate for normal growth (NORM). At
      12 months, the negative relationship between birth weight and indices of glucose
      metabolism persisted in ADLIB females (for example, fasting glucose, r - 0.632; P
      < 0.03) but was absent in NORM females and in both male groups. Therefore, low
      birth-weight offspring from differentially achieved prenatal malnutrition exhibit
      an early adverse metabolic phenotype, and this can apparently be ameliorated by
      postnatal nutrition in females but not in males.

PMID- 21733296
TI  - How much should I eat? Situational norms affect young women's food intake during
      meal time.
AB  - Portion size and the intake of others have been found to influence people's food
      intake. No study, however, has tested the potential influences of both types of
      situational norms on intake during the same eating occasion. We experimentally
      tested the effects of manipulating portion size and the intake of others on young
      women's meal intake during a 20 min eating opportunity. An experimental design
      with a three (confederate's intake: small, standard, large) by two (portion size:
      small, standard) between-participants design was used. A total of eighty-five
      young women participated. Portion size and the confederate's intake both
      influenced young women's intake. Participants consumed more when offered a larger
      portion than when offered a smaller portion, and they also ate more when their
      eating companion ate more. The present results indicate that the effects of
      portion size and the intake of others were independent but additive. Thus, both
      types of situational norms might independently guide an individual's intake
      during a single eating occasion.

PMID- 21733297
TI  - Rich micronutrient fortification of locally produced infant food does not improve
      mental and motor development of Zambian infants: a randomised controlled trial.
AB  - It is uncertain whether multiple micronutrients benefit the mental and
      psychomotor development of young children in developing countries. We conducted a
      randomised double-blind controlled trial to evaluate the effect of a richly
      micronutrient-fortified v. a basal fortified porridge on mental and psychomotor
      development in Zambian infants. Infants (n 743) were randomised at age 6 months
      to receive either the richly fortified or the basal fortified infant food and
      were followed up until 18 months of age. All the infants were evaluated monthly
      for achievement of a series of developmental milestones. The Bayley scales of
      infant development II were administered to a subsample of 502 infants at 6, 12
      and 18 months. Rich micronutrient fortification had no significant benefit on the
      following: (a) number of developmental milestones achieved (rate ratio at 12
      months = 1.00; 95 % CI 0.96, 1.05; P = 0.81, adjusted for sex, socio-economic
      status and maternal education, with similar results at 15 and 18 months); (b)
      ages of walking unsupported (hazard ratio (HR) 1.04; 95 % CI 0.88, 1.24; P =
      0.63, adjusted for the above covariates) and of speaking three or four clear
      words (HR 1.01; 95 % CI 0.84, 1.20; P = 0.94, adjusted for the above covariates);
      (c) mental development index (MDI) and psychomotor development index (PDI) of the
      Bayley scales (scores difference adjusted for baseline scores, age at the
      assessment, sex, socio-economic status, maternal education, language, age and HIV
      status: MDI 0.3 (95 % CI - 0.5, 1.1), P = 0.43; PDI - 0.1 (95 % CI - 0.9, 0.7), P
      = 0.78). In conclusion, the results do not support the hypothesis that rich
      micronutrient fortification improves Zambian infants' mental and motor
      development.

PMID- 21733298
TI  - Value and pitfalls in iodine fortification and supplementation in the 21st
      century.
AB  - Although the number of iodine-deficient countries has been reduced by almost 50 %
      over the last decade, it still remains a frequently misunderstood health problem.
      The most devastating effects of iodine deficiency occur during fetal development
      and childhood, periods in which sufficient iodine delivery remains critical.
      Besides the determination of thyroid size, the concentration of urinary iodine,
      serum thyroid-stimulating hormone and serum thyroglobulin are useful biomarkers
      to assess iodine status. Severe iodine deficiency is associated with neurological
      complications, cretinism, endemic goitre development, hypothyroidism, decreased
      fertility and increased infant mortality. The recommended iodine supplementation
      strategies are based on correction of iodine deficiency, close monitoring and
      evaluation of iodine administration, cooperation of the salt industry, training
      of local health care professionals and education of the population. Besides the
      multiple beneficial effects of supplementation, we present in this review a
      critical look at the possible side effects.

PMID- 21733299
TI  - Maternal low-protein diet-induced delayed reflex ontogeny is attenuated by
      moderate physical training during gestation in rats.
AB  - We evaluated the effects of moderate- to low-intensity physical training during
      gestation on reflex ontogeny in neonate rats whose mothers were undernourished.
      Virgin female Wistar rats were divided into four groups as follows: untrained
      (NT, n 7); trained (T, n 7); untrained with a low-protein diet (NT+LP, n 7);
      trained with a low-protein diet (T+LP, n 4). Trained rats were subjected to a
      protocol of moderate physical training on a treadmill over a period of 4 weeks (5
      d/week and 60 min/d, at 65 % of VO2max). After confirming the pregnancy, the
      intensity and duration of the exercise were reduced. Low-protein groups were
      provided with an 8 % casein diet, and controls were provided with a 17 % casein
      diet. Their respective offspring were evaluated (during the 10th-17th days of
      postnatal life) in terms of physical feature maturation, somatic growth and
      reflex ontogeny. Pups born to mothers provided with the low-protein diet during
      gestation and lactation showed delayed physical feature and reflex maturation and
      a deficit in somatic growth when compared with controls. However, most of these
      deficiencies were attenuated in pups of undernourished mothers undergoing
      training. In conclusion, physical training during gestation attenuates the
      effects of perinatal undernutrition on some patterns of maturation in the central
      nervous system during development.

PMID- 21733300
TI  - Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene
      variants in African Americans and European Americans with diabetes or the
      metabolic syndrome.
AB  - Over the past 50 years, increases in dietary n-6 PUFA, such as linoleic acid,
      have been hypothesised to cause or exacerbate chronic inflammatory diseases. The
      present study examines an individual's innate capacity to synthesise n-6 long
      chain PUFA (LC-PUFA) with respect to the fatty acid desaturase (FADS) locus in
      Americans of African and European descent with diabetes or the metabolic
      syndrome. Compared with European Americans (EAm), African Americans (AfAm)
      exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7.9 (sd
      2.1), AfAm 9.8 (sd 1.9) % of total fatty acids; P < 2.29 * 10-9) and the AA:n-6
      precursor fatty acid ratio, which estimates FADS1 activity (EAm 5.4 (sd 2.2),
      AfAm 6.9 (sd 2.2); P = 1.44 * 10-5). In all, seven SNP mapping to the FADS locus
      revealed strong association with AA, EPA and dihomo-gamma-linolenic acid (DGLA)
      in the EAm. Importantly, EAm homozygous for the minor allele (T) had
      significantly lower AA levels (TT 6.3 (sd 1.0); GG 8.5 (sd 2.1); P = 3.0 * 10-5)
      and AA:DGLA ratios (TT 3.4 (sd 0.8), GG 6.5 (sd 2.3); P = 2.2 * 10-7) but higher
      DGLA levels (TT 1.9 (sd 0.4), GG 1.4 (sd 0.4); P = 3.3 * 10-7) compared with
      those homozygous for the major allele (GG). Allele frequency patterns suggest
      that the GG genotype at rs174537 (associated with higher circulating levels of
      AA) is much higher in AfAm (0.81) compared with EAm (0.46). Similarly, marked
      differences in rs174537 genotypic frequencies were observed in HapMap
      populations. These data suggest that there are probably important differences in
      the capacity of different populations to synthesise LC-PUFA. These differences
      may provide a genetic mechanism contributing to health disparities between
      populations of African and European descent.

PMID- 21733301
TI  - Therapeutic effect of antisecretory factor-rich egg yolk on the late phases of
      2,4,6-trinitrobenzenesulphonic acid colitis in mice.
AB  - Antisecretory factor (AF) is expressed in all tissues of mammals, inhibits
      intestinal hypersecretion and has anti-inflammatory properties as well.
      Endogenous AF synthesis may be stimulated by feeding hydrothermally processed
      cereals. Alternatively, freeze-dried egg yolk can be used as a source of
      exogenous AF. Several reports have suggested that AF from freeze-dried egg yolk
      may be useful in inflammatory bowel disease. We assessed the effect of freeze
      dried, AF-rich egg yolk intake on 2,4,6-trinitrobenzenesulphonic acid (TNBS)
      colitis. Balb/c mice were randomised to receive (1) AF in sterile drinking-water
      (4 g/l, n 38) and (2) sterile drinking-water alone (vehicle, n 38) from TNBS or
      saline administration onwards. Different subsets of mice were killed at weeks 1-3
      after TNBS or saline administration. Macroscopic and microscopic damage was
      assessed in colonic specimens. Eicosanoid and cytokine production was evaluated
      in supernatants of 24 h-incubated colonic explants. Myeloperoxidase activity was
      measured in frozen colonic samples, while apoptosis was assessed in paraffined
      samples by the in situ oligoligation method. AF-treated mice showed a milder
      colonic damage compared with the vehicle group, which became statistically
      significant at week 3. This was accompanied by decreased IL-2, IL-1 and
      leukotriene B4 production at weeks 2 and 3, as well as increased interferon-gamma
      at week 1, in AF-treated mice compared with vehicle-treated mice. AF-treated mice
      had significantly increased counts of apoptotic cells in the lamina propria at
      weeks 1 and 2 post-TNBS. In conclusion, the administration of AF-rich egg yolk
      has a therapeutic effect in the late phases of TNBS colitis in Balb/c mice.

PMID- 21733302
TI  - Hepatic expression of sodium-dependent vitamin C transporters: ontogeny,
      subtissular distribution and effect of chronic liver diseases.
AB  - Ascorbic acid uptake is a key step in determining the overall bioactivity of this
      vitamin. Expression of Na-dependent vitamin C transporters (SVCT; SLC23A1 and
      SLC23A2) during long-term oxidative stress occurring in several chronic liver
      diseases may determine the antioxidant defence in this organ. In patients with
      hepatocellular cholestasis, primary biliary cirrhosis, haemochromatosis and non
      alcoholic steatohepatitis, using real-time RT-PCR, an enhanced hepatic expression
      of both SLC23A1 and SLC23A2, but not other organic anions transporters, such as
      OATP1A2, OATP1B1 and OATP1B3, was found. To further investigate these findings,
      we used secondary biliary cirrhosis induced in rats by long-term biliary
      obstruction as a model of chronic liver disease accompanied by oxidative stress
      because of bile acid accumulation. In control rat liver, expression of Slc23a1
      was low at birth, increased progressively up to adulthood and decreased in
      senescence, whereas expression of Slc23a2 did not change significantly after
      birth. In 8-week-old rats, immunohistochemistry and confocal microscopy studies
      revealed the expression in hepatocytes and bile duct cells of mainly Slc23a1,
      whereas both Slc23a1 and Slc23a2 were expressed in endothelial, stellate and
      Kupffer cells. In adult rats, when obstructive cholestasis was maintained for 8
      weeks, a significant up-regulation of Slc23a2 accompanied by a down-regulation of
      Slc23a1 was found. In sum, there is a selective cell-type distribution of SVCT in
      the liver tissue, which, in addition to differential control in the expression of
      both isoforms, may play a role in the ability of different liver cell types to
      take up vitamin C under physiological and pathological conditions.

PMID- 21733303
TI  - Effects of short-term feeding of Bt MON810 maize on growth performance, organ
      morphology and function in pigs.
AB  - Male weanling pigs (n 32) with a mean initial body weight of 7.5 kg and a mean
      weaning age of 28 d were used in a 31 d study to investigate the effects of
      feeding GM (Bt MON810) maize on growth performance, intestinal histology and
      organ weight and function. At weaning, the pigs were fed a non-GM starter diet
      during a 6 d acclimatisation period. The pigs were then blocked by weight and
      litter ancestry and assigned to diets containing 38.9 % GM (Bt MON810) or non-GM
      isogenic parent line maize for 31 d. Body weight and feed disappearance were
      recorded on a weekly basis (n 16/treatment), and the pigs (n 10/treatment) were
      killed on day 31 for the collection of organ, tissue and blood samples. GM maize
      fed pigs consumed more feed than the control pigs during the 31 d study (P <
      0.05) and were less efficient at converting feed to gain during days 14-30 (P <
      0.01). The kidneys of the pigs fed GM maize tended to be heavier than those of
      control pigs (P = 0.06); however, no histopathological changes or alterations in
      blood biochemistry were evident. Small intestinal morphology was not different
      between treatments. However, duodenal villi of GM maize-fed pigs tended to have
      fewer goblet cells/MUm of villus compared with control pigs (P = 0.10). In
      conclusion, short-term feeding of Bt MON810 maize to weaned pigs resulted in
      increased feed consumption, less efficient conversion of feed to gain and a
      decrease in goblet cells/MUm of duodenal villus. There was also a tendency for an
      increase in kidney weight, but this was not associated with changes in
      histopathology or blood biochemistry. The biological significance of these
      findings is currently being clarified in long-term exposure studies in pigs.

PMID- 21733304
TI  - Reported zinc, but not copper, intakes influence whole-body bone density, mineral
      content and T score responses to zinc and copper supplementation in healthy
      postmenopausal women.
AB  - A supplementation trial starting with 224 postmenopausal women provided with
      adequate vitamin D and Ca was conducted to determine whether increased Cu and Zn
      intakes would reduce the risk for bone loss. Healthy women aged 51-80 years were
      recruited for a double-blind, placebo-controlled study. Women with similar
      femoral neck T scores and BMI were randomly assigned to two groups of 112 each
      that were supplemented daily for 2 years with 600 mg Ca plus maize starch placebo
      or 600 mg Ca plus 2 mg Cu and 12 mg Zn. Whole-body bone mineral contents,
      densities and T scores were determined biannually by dual-energy X-ray
      absorptiometry, and 5 d food diaries were obtained annually. Repeated-measures
      ANCOVA showed that bone mineral contents, densities and T scores decreased from
      baseline values to year 2. A priori contrasts between baseline and year 2
      indicated that the greatest decreases occurred with Cu and Zn supplementation.
      Based on 5 d food diaries, the negative effect was caused by Zn and mainly
      occurred with Zn intakes >= 8.0 mg/d. With Zn intakes < 8.0 mg/d, Zn
      supplementation apparently prevented a significant decrease in whole-body bone
      densities and T scores. Food diaries also indicated that Mg intakes < 237 mg/d,
      Cu intakes < 0.9 mg/d and Zn intakes < 8.0 mg/d are associated with poorer bone
      health. The findings indicate that Zn supplementation may be beneficial to bone
      health in postmenopausal women with usual Zn intakes < 8.0 mg/d but not in women
      consuming adequate amounts of Zn.

PMID- 21733305
TI  - On a refinement of the 13C-mixed TAG breath test.
AB  - The present study was aimed to improve and simplify the 13C-mixed TAG (13C-MTG)
      breath test while keeping it acceptable for the patient. Healthy volunteers (ten
      women and eight men) were examined on four occasions, receiving in a random order
      300 mg 13C-MTG: (1) contained in two wafers; (2) administered with a 50 g wheat
      roll; as well as given with either (3) 10 or (4) 30 g butter, spread onto a 50 g
      wheat roll, as the test meal, respectively. Samples of expiratory air were taken
      for 6 h postprandially for the mass spectroscopic measurement of 13CO2
      enrichment. After intake of the sole 13C-MTG, the cumulative 13C recovery in
      breath air (AUC) appeared to be unsatisfactory, as after 6 h it did not exceed 10
      %. Application of the substrate with the 50 g wheat roll did not bring about any
      improvement in this parameter. The addition of the unlabelled fat to the test
      meal dramatically increased the cumulative 13C recovery. However, we found higher
      values for the momentary 13C recovery and AUC with 10 g butter compared with 30
      g. It can be concluded that: (1) addition of unlabelled fat is indispensable to
      obtain a proper course of the breath 13C elimination during the conduct of the
      13C-MTG breath test and (2) it is possible to apply a considerably smaller amount
      of the unlabelled fat than has previously been recommended for this test.

PMID- 21733306
TI  - The assessment of vascular function during dietary intervention trials in human
      subjects.
AB  - The potential to reduce cardiovascular morbidity through dietary modification
      remains an area of intense clinical and scientific interest. Any putatively
      beneficial intervention should be tested within a randomised controlled trial
      which records appropriate endpoints, ideally incident CVD and death. However, the
      large sample sizes required for these endpoints and associated high costs mean
      that the majority of dietary intervention research is conducted over short
      periods among either healthy volunteers or those at only slightly increased risk,
      with investigators using a diverse range of surrogate measures to estimate
      arterial health in these studies. The present review identifies commonly employed
      techniques, discusses the relative merits of each and highlights emerging
      approaches.

PMID- 21733307
TI  - High-fructose feeding impacts on the adrenergic control of renal haemodynamics in
      the rat.
AB  - The present study explored the hypothesis that a prolonged 8 weeks exposure to a
      high fructose intake suppresses adrenergic and angiotensin II (Ang II)-mediated
      vasoconstriction and is associated with a higher contribution of alpha1D
      adrenoceptors. A total of thirty-two Sprague-Dawley rats received either 20 %
      fructose solution (FFR) or tap water (control, C) to drink ad libitum for 8
      weeks. Metabolic and haemodynamic parameters were assessed weekly. The renal
      cortical vasoconstrictor responses to noradrenaline (NA), phenylephrine (PE),
      methoxamine (ME) and Ang II were determined in the presence and absence of
      BMY7378 (alpha1D-adrenoceptor antagonist). FFR had increased blood pressure,
      plasma levels of glucose, TAG and insulin. FFR expressed reduced renal vascular
      responses to adrenergic agonists and Ang II (NA: 50 %, PE: 50 %, ME, 65 %, Ang
      II: 54 %). Furthermore in the C group, the magnitude of the renal cortical
      vasoconstriction to all agonists was blunted in the presence of the low or high
      dose of BMY7378 (NA: 30 and 31 %, PE: 23 and 33 %, ME: 19 and 44 %, Ang II: 53
      and 77 %), respectively, while in the FFR, vasoconstriction was enhanced to
      adrenergic agonists and reduced to Ang II (NA: 8 and 83 %, PE: 55 %, ME, 2 and
      177 %, Ang II: 61 and 31 %). Chronic high fructose intake blunts vascular
      sensitivity to adrenergic agonists and Ang II. Moreover, blocking of the alpha1D
      adrenoceptor subtype results in enhancement of renal vasoconstriction to
      adrenergic agonists, suggesting an inhibitory action of alpha1D-adrenoceptors in
      the FFR. alpha1D-Adrenoceptors buffer the AT1-receptor response in the renal
      vasculature of normal rats and fructose feeding suppressed this interaction.

PMID- 21733308
TI  - Medium-chain fatty acid nanoliposomes suppress body fat accumulation in mice.

PMID- 21733309
TI  - Whole grain consumption has a modest effect on the development of diabetes in the
      Goto-Kakisaki rat.
AB  - Epidemiological evidence suggests that whole grain intake is associated with
      reduced risk of type 2 diabetes. However, studies of individual whole grains on
      the prevention of type 2 diabetes are lacking. The objective of the present study
      was to examine the effect of different whole grains on type 2 diabetes in an
      animal model of type 2 diabetes, the Goto-Kakisaki (GK) rat. GK rats were fed
      either a basal diet or a whole grain-containing diet for 5 months. Whole grain
      diets contained 65 % whole grain flours of wheat, barley, oats or maize. After 2
      months of feeding, fasting plasma glucose concentrations were lower in the wheat,
      barley and oats groups, compared with the basal group, whereas glycated Hb was
      significantly greater in the wheat group compared with other groups. Feeding of
      whole barley and maize increased plasma C-peptide concentrations compared with
      whole wheat at 2 months. There was a trend in the improvement of insulin
      resistance with a consumption of barley and oats diets at 2 months (P = 0.06)
      compared with the basal diet. Oxidative stress markers, urinary thiobarbituric
      acid-reactive substances and 8-isoprostane, did not improve with whole grain
      intake at 2 months. At 5 months, whole grain diets did not differ from the basal
      diet in glycaemic control, insulin secretion, oxidative stress and preservation
      of pancreatic beta-cell mass. These results suggest that the consumption of whole
      grains may offer modest benefit early in the development of type 2 diabetes, but
      this benefit is lost with further development of the disease.

PMID- 21733310
TI  - Analysis of the erosive effect of different dietary substances and medications.
AB  - Excessive consumption of acidic drinks and foods contributes to tooth erosion.
      The aims of the present in vitro study were twofold: (1) to assess the erosive
      potential of different dietary substances and medications; (2) to determine the
      chemical properties with an impact on the erosive potential. We selected sixty
      agents: soft drinks, an energy drink, sports drinks, alcoholic drinks, juice,
      fruit, mineral water, yogurt, tea, coffee, salad dressing and medications. The
      erosive potential of the tested agents was quantified as the changes in surface
      hardness (DeltaSH) of enamel specimens within the first 2 min (DeltaSH2-0 = SH2
      min - SHbaseline) and the second 2 min exposure (DeltaSH4-2 = SH4 min - SH2 min).
      To characterise these agents, various chemical properties, e.g. pH,
      concentrations of Ca, Pi and F, titratable acidity to pH 7.0 and buffering
      capacity at the original pH value (beta), as well as degree of saturation (pK -
      pI) with respect to hydroxyapatite (HAP) and fluorapatite (FAP), were determined.
      Erosive challenge caused a statistically significant reduction in SH for all
      agents except for coffee, some medications and alcoholic drinks, and non
      flavoured mineral waters, teas and yogurts (P < 0.01). By multiple linear
      regression analysis, 52 % of the variation in DeltaSH after 2 min and 61 % after
      4 min immersion were explained by pH, beta and concentrations of F and Ca (P <
      0.05). pH was the variable with the highest impact in multiple regression and
      bivariate correlation analyses. Furthermore, a high bivariate correlation was
      also obtained between (pK - pI)HAP, (pK - pI)FAP and DeltaSH.

PMID- 21733311
TI  - Increased Mauthner cell activity and escaping behaviour in seabream fed long
      chain PUFA.
AB  - There is limited information on the specific effects of long-chain PUFA (LCPUFA)
      on neuron development and functioning. Deficiency of those essential fatty acids
      impairs escape and avoidance behaviour in fish, where Mauthner cells (M-cells)
      play a particularly important role in initiating this response. Gilthead seabream
      larvae fed two different LCPUFA profiles were challenged with a sonorous
      stimulus. Feeding n-3 LCPUFA increased the content of these fatty acids in fish
      tissues and caused a higher number of larvae to react to the stimulus with a
      faster burst swimming speed response. This faster startle response in fish fed n
      3 LCPUFA was also associated with an increased immune-positive neural response,
      particularly in M-cells, denoting a higher production of acetylcholine. The
      present study shows the first evidence of the effect of n-3 LCPUFA on the
      functioning of particular neurons in fish, the M-cells and the behaviour response
      that they modulate to escape from a sound stimulus.

PMID- 21733312
TI  - Is physical activity in weight management more about 'calories in' than 'calories
      out'?

PMID- 21733313
TI  - Glyceollins inhibit platelet-derived growth factor-mediated human arterial smooth
      muscle cell proliferation and migration.
AB  - Platelet-derived growth factor (PDGF)-BB can induce abnormal proliferation and
      migration of vascular smooth muscle cells (VSMC) that are involved in the
      development of CVD. In our preliminary study, phytoalexin glyceollins
      (glyceollins I, II and III) isolated from soyabean seeds cultured with
      Aspergillus sojae showed strong antioxidant and anti-inflammatory activity. Since
      antioxidants showed beneficial effects on chronic inflammatory diseases, the
      purpose of the present study was to examine the effects of glyceollins on PDGF
      induced proliferation and migration in human aortic smooth muscle cells (HASMC).
      Incubation of resting HASMC with glyceollins for 24 h significantly diminished
      PDGF-increased cell number and DNA synthesis in a dose-dependent manner without
      any cytotoxicity. In addition to blocking of the PDGF-inducible progression
      through the G0/G1 to the S phase of the cell cycle, glyceollins down-regulated
      the expression of cyclin-dependent kinase (CDK)2 and cyclin D1, and up-regulated
      the expression of CDK inhibitors such as p27kip1 and p53.Glyceollins also
      effectively inhibited reactive oxygen species generation and phosphorylation of
      PDGF receptor-beta, phospholipase Cgamma1, Akt and extracellular signal-regulated
      kinase 1/2 by PDGF stimulation. Furthermore, glyceollins were found to inhibit
      PDGF-induced dissociation of actin filaments and cell migration. Thus, the
      results suggest that glyceollins could become a potent therapeutic agent for
      regulating VSMC-associated vascular disease such as atherosclerosis and
      restenosis after angioplasty.

PMID- 21733314
TI  - Mediterranean diet adherence during pregnancy and fetal growth: INMA (Spain) and
      RHEA (Greece) mother-child cohort studies.
AB  - Dietary intake of specific nutrients or food groups during pregnancy could
      influence fetal growth, but scant evidence is available on effects of dietary
      patterns. The aim of this study was to evaluate the impact of Mediterranean diet
      (MD) adherence during pregnancy on fetal growth in two population-based mother
      child cohorts in Spain and Greece. We studied 2461 mother-newborn pairs from the
      Spanish multi-centre 'INMA' study (Atlantic area: INMA-Atlantic; Mediterranean
      area: INMA-Mediterranean), and 889 pairs from the 'RHEA' study in Crete, Greece.
      Maternal diet during pregnancy was assessed by FFQ and MD adherence was evaluated
      through an a priori score. Fetal growth restriction was based on a customised
      model, and multivariate log-binomial and linear regression models were used to
      adjust for several confounders. MD scores differ significantly between the
      cohorts with women in INMA-Atlantic reporting higher intakes of fish and dairy
      products, while women in the Mediterranean area reported higher intakes of
      cereals, vegetables and fruits. Women with high MD adherence had a significantly
      lower risk of delivering a fetal growth-restricted infant for weight (risk
      ratios: 0.5; 95 % CI 0.3, 0.9) in the INMA-Mediterranean cohort. Stratified
      analysis by smoking revealed that higher MD adherence increased birth weight and
      birth length in smoking mothers, whereas this effect was not apparent in non
      smoking mothers. The results of the present study show that several types of MD
      exist across European Mediterranean regions. High MD adherence may modify the
      detrimental effect of smoking on birth size, but overall effects of diet were not
      universal for the studies in this analysis.

PMID- 21733315
TI  - Soya protein- and casein-based nutritionally complete diets fed during gestation
      and lactation differ in effects on characteristics of the metabolic syndrome in
      male offspring of Wistar rats.
AB  - The AIN-93G diets based on soya protein or casein were fed to pregnant Wistar
      rats from day 3 of gestation and compared for their effects on characteristics of
      the metabolic syndrome in male offspring. Pregnant rats were randomised to either
      a casein (C) or soya protein (S) diet (n 12) during gestation only (Expt 1) or
      during gestation and lactation (Expt 2). Male offspring were weaned to either a C
      or S diet for 9 weeks (Expt 1) or 15 weeks (Expt 2). In Expt 1, pups born to S
      fed dams had higher fasting blood glucose (BG), systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) at week 4, higher blood glucose (BG) response to a
      glucose administration (P < 0.001) and higher body weight (BW) at week 8 (P <
      0.05). In Expt 2, consumption of the S diet throughout gestation and lactation
      resulted in higher BW (P < 0.05), DBP (P < 0.005) and SBP (P < 0.005) in the
      offspring. They also had higher homeostasis model assessment of insulin
      resistance (HOMA-IR; P < 0.05) and plasma homocysteine (P < 0.05) at weaning,
      higher fasting BG and glucose response to glucose administration (P < 0.005) at
      week 12 and higher HOMA-IR (P < 0.01) at week 15. Although composition of the
      weaning diets interacted with the diet of the dams, the latter was the dominant
      factor in determining metabolic outcomes in the offspring. In conclusion, the S
      diet, compared with the C diet, when consumed during gestation or throughout
      gestation and lactation increased the presence of characteristics of the
      metabolic syndrome in the offspring.

PMID- 21733316
TI  - Saturated fatty acids activate microglia via Toll-like receptor 4/NF-kappaB
      signalling.
AB  - Diets rich in SFA have been implicated in Alzheimer's disease (AD). There is
      strong evidence to suggest that microglial activation augments the progression of
      AD. However, it remains uncertain whether SFA can initiate microglial activation
      and whether this response can cause neuronal death. Using the BV-2 microglial
      cell line and primary microglial culture, we showed that palmitic acid (PA) and
      stearic acid (SA) could activate microglia, as assessed by reactive morphological
      changes and significantly increased secretion of pro-inflammatory cytokines, NO
      and reactive oxygen species, which trigger primary neuronal death. In addition,
      the mRNA level of these pro-inflammatory mediators determined by RT-PCR was also
      increased by PA and SA. We further investigated the intracellular signalling
      mechanism underlying the release of pro-inflammatory mediators from PA-activated
      microglial cells. The present results showed that PA activated the
      phosphorylation and nuclear translocation of the p65 subunit of NF-kappaB.
      Furthermore, pyrrolidine dithiocarbamate, a NF-kappaB inhibitor, attenuated the
      production of pro-inflammatory mediators except for IL-6 in PA-stimulated
      microglia. Administration of anti-Toll-like receptor (TLR)4-neutralising antibody
      repressed PA-induced NF-kappaB activation and pro-inflammatory mediator
      production. In conclusion, the present in vitro study demonstrates that SFA could
      activate microglia and stimulate the TLR4/NF-kappaB pathway to trigger the
      production of pro-inflammatory mediators, which may contribute to neuronal death.

PMID- 21733317
TI  - Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat
      diet.
AB  - Consumption of fruits and vegetables has been investigated for their role in the
      prevention of many chronic conditions. Among the fruits, mango provides numerous
      bioactive compounds such as carotenoids, vitamin C and phenolic compounds, which
      have been shown to have antioxidant and anti-inflammatory properties. The present
      study examined the effects of dietary supplementation of freeze-dried mango pulp,
      in comparison with the hypolipidaemic drug, fenofibrate, and the hypoglycaemic
      drug, rosiglitazone, in reducing adiposity and alterations in glucose metabolism
      and lipid profile in mice fed a high-fat (HF) diet. Male C57BL/6J mice were
      randomly divided into six treatment groups (eight to nine/group): control (10 %
      energy from fat); HF (60 % energy from fat); HF+1 or 10 % freeze-dried mango
      (w/w); HF+fenofibrate (500 mg/kg diet); HF+rosiglitazone (50 mg/kg diet). After 8
      weeks of treatment, mice receiving the HF diet had a higher percentage body fat
      (P = 0.0205) and epididymal fat mass (P = 0.0037) compared with the other
      treatment groups. Both doses of freeze-dried mango, similar to fenofibrate and
      rosiglitazone, prevented the increase in epididymal fat mass and the percentage
      of body fat. Freeze-dried mango supplementation at the 1 % dose improved glucose
      tolerance as shown by approximately 35 % lower blood glucose area under the curve
      compared with the HF group. Moreover, freeze-dried mango lowered insulin
      resistance, as indicated by the homeostasis model assessment of insulin
      resistance, to a similar extent as rosiglitazone and modulated NEFA. The present
      findings demonstrate that incorporation of freeze-dried mango in the diet of mice
      improved glucose tolerance and lipid profile and reduced adiposity associated
      with a HF diet.

PMID- 21733318
TI  - Lupin seed gamma-conglutin lowers blood glucose in hyperglycaemic rats and
      increases glucose consumption of HepG2 cells.
AB  - The aim of the present study was to evaluate the effect of a chronic oral gamma
      conglutin treatment in male Sprague-Dawley rats in which hyperglycaemia had been
      induced by supplying 10 % d-glucose in drinking-water. A gamma-conglutin dosage
      of 28 mg/kg body weight was daily administered to animals for 21 d. Plasma
      glucose, insulin and glucose overloading were monitored. Chronic administration
      of glucose resulted in a statistically significant (P < 0.05) increase in fasting
      blood glucose (2.5-fold) and insulin (2.7-fold) v. the values recorded in control
      rats. Simultaneous treatment with gamma-conglutin attenuated the rise in plasma
      glucose (1.9-fold) and insulin (1.8-fold) levels in the glucose-fed rats (P <
      0.05). Fasting insulin and homeostasis model of insulin resistance were decreased
      by 34 and 48 % (P < 0.05), respectively, in the gamma-conglutin-treated rats v.
      the values found in pair-fed animals. To confirm these results with a different
      approach, HepG2 cells, grown for 24 and 48 h in Dulbecco's minimum essential
      medium containing different glucose concentrations (5.5, 11.1 and 16.5 mmol/l),
      were exposed to 10 MUmol/l gamma-conglutin with or without 10 mmol/l metformin or
      100 nmol/l insulin. gamma-Conglutin increased glucose consumption (from 1.5- to
      2.5-fold) in HepG2 cells, under all experimental conditions; this effect was more
      evident after 48 h incubation. Moreover, in this in vitro model, the addition of
      gamma-conglutin potentiated the activity of insulin and metformin in cell glucose
      consumption. These findings extend the previous ones and suggest the potential
      use of lupin gamma-conglutin in the control of glycaemia.

PMID- 21733319
TI  - Measured energy value of pistachios in the human diet.
AB  - Previous studies have suggested that lipid from nuts is more poorly absorbed than
      that from other food sources. If lipid from nuts is poorly absorbed, then the
      metabolisable energy contained in the nuts is less than that predicted by the
      Atwater general factors. A crossover feeding study was conducted in which sixteen
      volunteers consumed pistachios for 3 weeks as part of a controlled diet.
      Pistachio doses were 0, 42 and 84 g/d. Urine and faecal samples were collected,
      and urine, faeces and diet were analysed for N, fat, total dietary fibre, ash and
      combustible energy. Blood was also collected after each treatment period and
      analysed for plasma lipids. Energy value of pistachio nuts was calculated from
      differences in energy excretion during the different dietary treatments. The
      measured energy density of pistachios was found to be 22.6 kJ/g, which is 5 %
      less than the currently accepted energy value of 23.7 kJ/g, as calculated using
      the Atwater general factors. The pistachio nut intervention lowered LDL
      cholesterol by 6 %, but did not significantly change plasma total cholesterol,
      HDL-cholesterol or TAG. In conclusion, pistachio nuts contain less metabolisable
      energy than that calculated from the Atwater general factors. Accurate
      information about metabolisable energy content of foods is important for reliable
      food labelling.

PMID- 21733320
TI  - Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol
      response to supplementation in healthy young and older Irish adults.
AB  - There is increasing epidemiological evidence linking sub-optimal vitamin D status
      with overweight and obesity. Although increasing BMI and adiposity have also been
      negatively associated with the change in vitamin D status following
      supplementation, results have been equivocal. The aim of this randomised, placebo
      controlled study was to investigate the associations between anthropometric
      measures of adiposity and the wintertime serum 25-hydroxycholecalciferol
      (25(OH)D) response to 15 MUg cholecalciferol per d in healthy young and older
      Irish adults. A total of 110 young adults (20-40 years) and 102 older adults ( >=
      64 years) completed the 22-week intervention with >85 % compliance. The change in
      25(OH)D from baseline was calculated. Anthropometric measures of adiposity taken
      at baseline included height, weight and waist circumference (WC), along with
      skinfold thickness measurements to estimate fat mass (FM). FM was subsequently
      expressed as FM (kg), FM (%), FM index (FMI (FM kg/height m2)) and as a
      percentage ratio to fat-free mass (FFM). In older adults, vitamin D status was
      inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and
      FM:FFM (%) at baseline (r - 0.33, - 0.36, - 0.33, - 0.30, - 0.33 and - 0.27,
      respectively, all P values < 0.01). BMI in older adults was also negatively
      associated with the change in 25(OH)D following supplementation (beta - 1.27, CI 
      2.37, - 0.16, P = 0.026); however, no such associations were apparent in younger
      adults. Results suggest that adiposity may need to be taken into account when
      determining an adequate wintertime dietary vitamin D intake for healthy older
      adults residing at higher latitudes.

PMID- 21733321
TI  - High-fat diet causes increased serum insulin and glucose which synergistically
      lead to renal tubular lipid deposition and extracellular matrix accumulation.
AB  - Renal tubular lipid accumulation is associated with renal injury in the metabolic
      syndrome, but its mechanisms are not fully elucidated. The purpose of the present
      study was to investigate the exact mechanism of renal tubular lipid accumulation
      in the diet-induced metabolic syndrome. The in vivo experiments showed that a
      high-fat diet induced hyperglycaemia, hyperinsulinaemia and
      hypertriacylglycerolaemia, subsequent increases in sterol regulatory element
      binding protein-1 (SREBP-1) and transforming growth factor-beta1 (TGF-beta1),
      lipid droplet deposit in renal tubular cells and interstitial extracellular
      matrix accumulation in Wistar rats. A human renal proximal tubular epithelial
      cell line (HKC) was used to determine the direct role of insulin, and the results
      revealed that insulin induced SREBP-1, fatty acid synthase (FASN), TGF-beta1
      expressions, lipid droplet and extracellular matrix deposits. Knockdown of SREBP
      1 by RNA interference technology significantly inhibited FASN, TGF-beta1 up
      regulation, lipid and extracellular matrix accumulation caused by insulin. In
      addition, we found that insulin and high glucose could synergistically increase
      SREBP-1, FASN, TGF-beta1 and fibronectin expressions in HKC cells. These results
      indicate that high-fat diet-induced increased serum insulin and glucose
      synergistically cause renal tubular lipid deposit and extracellular matrix
      accumulation via the SREBP-1 pathway.

PMID- 21733322
TI  - Reduction of monocyte chemoattractant protein 1 and macrophage migration
      inhibitory factor by a polyphenol-rich extract in subjects with clustered
      cardiometabolic risk factors.
AB  - Inflammation is a hallmark of the metabolic syndrome, which also contributes to a
      pro-atherogenic state. NF-kappaB activation, a critical step in regulating
      inflammatory reactions, can be inhibited by polyphenol (PF) extracts, at least in
      vitro. In the present study, we set out to study whether a PF-rich extract could
      attenuate the chronic inflammatory state and/or an acute immune response in vivo
      in subjects with clustered metabolic risk factors. A commercially available, PF
      rich extract (500 mg daily) or placebo was administered for 4 weeks to thirty
      four subjects with two or more metabolic risk factors using a randomised, double
      blind, cross-over design. During the final study visit, an acute inflammatory
      challenge (lipopolysaccharide (LPS) 1 ng/kg body weight) was administered to a
      random subgroup of subjects (PF-rich extract (n 12) and placebo (n 12)). The PF
      rich extract modestly reduced the inflammatory chemokines monocyte
      chemoattractant protein 1 (MCP-1) and macrophage migration inhibitory factor
      (MIF) (MCP-1 - 6.5 % (PF, median 116 (interquartile range 97-136) pg/ml v.
      placebo, median 124 (interquartile range 105-153) pg/ml; P < 0.05); MIF - 10.8 %
      (PF, median 2512 (interquartile range 1898-3972) pg/ml v. placebo, median 2814.5
      (interquartile range 2296-3852) pg/ml; P < 0.05); however, other measured markers
      of inflammation and cardiometabolic disease, such as C-reactive protein, IL-6,
      HDL-cholesterol, adiponectin and oxidised LDL, remained unaffected. Following the
      LPS challenge, we found a statistically significant 48 % reduction of MCP-1
      production in the PF-rich extract group (n 12) v. placebo (n 12) over 6 h (PF 766
      (sd 155) v. placebo 1466 (sd 989) ng/ml; P < 0.05, area under the curve). In
      conclusion, short-term oral administration of the PF-rich extract caused a modest
      anti-inflammatory effect in subjects with clustered metabolic risk factors.
      Further dose-ranging studies are needed to evaluate whether and to what extent PF
      rich extracts can be used to reduce the pro-inflammatory state in subjects with
      metabolic diseases at increased cardiovascular risk.

PMID- 21733323
TI  - Medium-chain fatty acid nanoliposomes suppress body fat accumulation in mice.
AB  - Medium-chain fatty acids (MCFA) are widely used in diets for patients with
      obesity. To develop a delivery system for suppressing dietary fat accumulation
      into adipose tissue, MCFA were encapsulated in nanoliposomes (NL), which can
      overcome the drawbacks of MCFA and keep their properties unchanged. In the
      present study, crude liposomes were first produced by the thin-layer dispersion
      method, and then dynamic high-pressure microfluidisation (DHPM) and DHPM combined
      with freeze-thawing methods were used to prepare MCFA NL (NL-1 and NL-2,
      respectively). NL-1 exhibited smaller average size (77.6 (SD 4.3) nm), higher
      zeta potential (- 40.8 (SD 1.7) mV) and entrapment efficiency (73.3 (SD 16.1) %)
      and better stability, while NL-2 showed narrower distribution (polydispersion
      index 0.193 (SD 0.016)). The body fat reduction property of NL-1 and NL-2 were
      evaluated by short-term (2 weeks) and long-term (6 weeks) experiments of mice. In
      contrast to the MCFA group, the NL groups had overcome the poor palatability of
      MCFA because the normal diet of mice was maintained. The body fat and total
      cholesterol (TCH) of NL-1 (1.54 (SD 0.30) g, P = 0.039 and 2.33 (SD 0.44) mmol/l,
      P = 0.021, respectively) and NL-2 (1.58 (SD 0.69) g, P = 0.041 and 2.29 (SD 0.38)
      mmol/l, P = 0.015, respectively) significantly decreased when compared with the
      control group (2.11 (SD 0.82) g and 2.99 (SD 0.48) mmol/l, respectively). The TAG
      concentration of the NL-1 group (0.55 (SD 0.14) mmol/l) was remarkably lower (P =
      0.045) than the control group (0.94 (SD 0.37) mmol/l). No significant difference
      in weight and fat gain, TCH and TAG was detected between the MCFA NL and MCFA
      groups. Therefore, MCFA NL could be potential nutritional candidates for obesity
      to suppress body fat accumulation.

PMID- 21733324
TI  - Chronic dietary supplementation of proanthocyanidins corrects the mitochondrial
      dysfunction of brown adipose tissue caused by diet-induced obesity in Wistar
      rats.
AB  - The present study aims to determine the effects of grape seed proanthocyanidin
      extract (GSPE) on brown adipose tissue (BAT) mitochondrial function in a state of
      obesity induced by diet. Wistar male rats were fed with a cafeteria diet (Cd) for
      4 months; during the last 21 d, two groups were treated with doses of 25 and 50
      mg GSPE/kg body weight. In the BAT, enzymatic activities of citrate synthase,
      cytochrome c oxidase (COX) and ATPase were determined and gene expression was
      analysed by real-time PCR. The mitochondrial function of BAT was determined in
      fresh mitochondria by high-resolution respirometry using both pyruvate and
      carnitine-palmitoyl-CoA as substrates. The results show that the Cd causes an
      important decrease in the gene expression of sirtuin 1, nuclear respiratory
      factor 1, isocitrate dehydrogenase 3gamma and COX5alpha and, what is more
      telling, decreases the levels of mitochondrial respiration both with pyruvate and
      canitine-palmitoyl-CoA. Most of these parameters, which are indicative of
      mitochondrial dysfunction due to diet-induced obesity, are improved by chronic
      supplementation of GSPE. The beneficial effects caused by the administration of
      GSPE are exhibited as a protection against weight gain, in spite of the Cd the
      rats were fed. These data indicate that chronic consumption of a moderate dose of
      GSPE can correct an energy imbalance in a situation of diet-induced obesity,
      thereby improving the mitochondrial function and thermogenic capacity of the BAT.

PMID- 21733325
TI  - Hepatoprotective and antioxidant activities of grapeseeds against ethanol-induced
      oxidative stress in rats.
AB  - The present study was carried out to evaluate the hepatoprotective effect and
      antioxidant role of grape (Vitis vinifera L.) seeds (GS) against ethanol-induced
      oxidative stress. The hepatoprotective and antioxidant roles of the GS
      supplementation feed against ethanol-induced oxidative stress were evaluated by
      measuring liver damage serum marker enzymes, aspartate aminotransferase, alanine
      aminotransferase, gamma-glutamyl transpeptidase and lactate dehydrogenase,
      antioxidant defence system such as GSH, glutathione reductase, superoxide
      dismutase, glutathione S-transferase and glutathione peroxidase and
      malondialdehyde (MDA) content in various tissues of rats. Rats were divided into
      four experimental groups: I (control), II (20 % ethanol), III (15 % GS) and IV
      (20 % ethanol+15 % GS). According to the results, the level of serum marker
      enzymes was significantly increased in group II as compared to that of group I,
      but decreased in group IV as compared to that of group II. Also, administration
      of GS-supplemented food restored the ethanol-induced MDA, which was increased
      near the control level. The results indicated that GS could be as important as
      diet-derived antioxidants in preventing oxidative damage in the tissues by
      reducing the lipid oxidation or inhibiting the production of ethanol-induced free
      radicals in rats.

PMID- 21733326
TI  - Resveratrol attenuates steatosis in obese Zucker rats by decreasing fatty acid
      availability and reducing oxidative stress.
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common
      manifestations of chronic liver disease worldwide. The aim of the present study
      was to assess the effect of resveratrol on liver fat accumulation, as well as on
      the activity of those enzymes involved in lipogenesis and fatty acid oxidation in
      fa/fa Zucker rats. A total of thirty rats were assigned to three experimental
      groups and orally treated with resveratrol for 6 weeks, or without resveratrol
      (C: control group; RSV15 group: 15 mg/kg body weight per d; RSV45 group: 45 mg/kg
      body weight per d). Liver histological analysis was performed by microscopy.
      Levels of hepatic carnitine palmitoyltransferase-Ia (CPT-Ia), acyl-coenzyme A
      oxidase (ACO), fatty acid synthase, glucose-6-phosphate dehydrogenase and malic
      enzyme were assessed by spectrophotometry, and acetyl-CoA carboxylase was
      assessed by radiometry. Commercial kits were used to determine serum TAG, NEFA,
      total HDL and non-HDL-cholesterol, glycerol, ketonic bodies, glucose, insulin,
      adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
      alkaline phosphatase (ALP), hepatic TAG, thiobarbituric acid reactive substrates,
      GSH (GSSG) and superoxide dismutase. Resveratrol reduced liver weight and TAG
      content. It did not modify the activity of lipogenic enzymes but it did increase
      CPT-Ia and ACO activities. NEFA and ALP were reduced in both resveratrol-treated
      groups. AST/GOT was reduced only by the lowest dose. ALT/GPT, TAG and adiponectin
      remained unchanged. Resveratrol reduced liver oxidative stress. This study
      demonstrates that resveratrol can protect the liver from NAFLD by reducing fatty
      acid availability. Moreover, resveratrol also protects liver from oxidative
      stress.

PMID- 21733327
TI  - The effects of repeated ingestion of high and low glucose-electrolyte solutions
      on gastric emptying and blood 2H2O concentration after an overnight fast.
AB  - The addition of carbohydrate to drinks designed to have a role in rehydrating the
      body is commonplace. The gastric emptying and fluid uptake characteristics
      following repeated ingestion of drinks with high and low glucose concentrations
      were examined in eight subjects (three male and five female). Following a 13 h
      fluid restriction period, the subjects ingested a volume of test solution
      amounting to 3 % of the initial body mass over a period of 60 min. Test drinks
      were 2 and 10 % glucose-electrolyte solutions with osmolalities of 189 (SD 3) and
      654 (SD 3) mOsm/kg, respectively. The initial bolus of each test solution
      contained 10 g of (2)H(2)O. Blood samples were collected throughout drinking and
      for 60 min afterwards. Gastric volumes were determined via gastric aspiration at
      15 min intervals for 120 min. No difference between trials in total stomach
      volume was observed until 30 min after the ingestion of the first bolus of test
      drink, but blood (2)H concentration was increased during both trials 10 min after
      ingestion of the first bolus. Blood (2)H concentration was greater at this time
      point during the 2 % glucose trial than during the 10 % glucose trial and
      remained higher for the duration of the trial with the exception of one time
      point. Urine volume at the end of the trial was greater in the 2 % glucose trial
      than in the 10 % glucose trial. It is concluded that the reduced overall rate of
      fluid uptake following ingestion of the 10 % glucose solution was due largely to
      a relatively slow rate of gastric emptying.

PMID- 21733328
TI  - Effect of gelatinisation of starch with casein proteins on incretin hormones and
      glucose transporters in vitro.
AB  - Foods that have a low glycaemic index or foods that contain slowly digestible
      starch are beneficial in controlling fluctuations in blood glucose and insulin
      levels. The study hypothesis is that gelatinisation of starch in structured
      casein networks provides a method for decreasing the digestion rate of the starch
      and, hence, minimising postprandial glucose fluctuations. This study examined the
      effect of starch gelatinisation with or without casein on (1) gene expression and
      peptide secretion levels of the incretin hormones glucagon-like peptide 1 and
      glucose-independent insulinotropic polypeptide and (2) gene expression of the
      sodium-glucose cotransporter and GLUT-2 in intestinal cell culture systems. The
      intestinal epithelial cell line, STC-1, and the enteroendocrine colonic cell
      line, Caco-2, were exposed to in vitro digested foods (starch gelatinised with
      alpha-casein, starch gelatinised with beta-casein and gelatinised starch alone).
      The encapsulation of starch with casein before in vitro digestion lowers levels
      of incretin hormone secretion. Digestion of starch gelatinised with casein also
      releases less glucose than starch alone as indicated by significantly (P < 0.05)
      lower levels of glucose transporter mRNA transcripts. Some subtle cellular
      response differences were observed following exposure to starch gelatinised with
      alpha- compared to beta-casein. Fractionation of alpha-casein and beta-casein by
      reverse-phase HPLC identified that fractions that differed in hydrophobicity
      differed significantly (P < 0.05) in their ability to promote secretion of the
      incretin hormones. Evidence suggests that gelatinisation of starch with casein
      may be a functional food ingredient that minimises blood glucose fluctuations.

PMID- 21733329
TI  - The confusion about dietary fatty acids recommendations for CHD prevention.
AB  - A recent meta-analysis of prospective cohort studies has not found an association
      between dietary saturated fat intake and CHD incidence. This funnelled the
      discussion about the importance of the recommendation to lower the intake of
      saturated fat for the prevention of CHD. At the same time a document of the
      European Food Safety Authority has suggested that specific quantitative
      recommendations are not needed for individual fatty acids but that more general
      statements can suffice. In this review, we discuss methodological aspects of the
      absence of association between SFA intake and CHD incidence in prospective cohort
      studies. We also summarise the results of the controlled dietary experiments on
      blood lipids and on CHD incidence in which saturated fat was replaced by either
      cis-unsaturated fat or carbohydrates. Finally, we propose a nutritionally
      adequate diet with an optimal fatty acid composition for the prevention of CHD in
      the context of dietary patterns. Such diets are characterised by a low intake of
      saturated fat, and as low as possible intake of trans-fat and fulfil the
      requirements for the intake of n-6 and n-3 fatty acids. No recommendation is
      needed for the intake of cis-MUFA.

PMID- 21733330
TI  - Bioavailability of vitamin B12 in cows' milk.
AB  - The natural source of vitamin B12 in human diets comes from animal products. For
      example, one glass (250 ml) of milk provides approximately 50 % of the RDA (2.4
      MUg/d). It was hypothesised that the provision of vitamin B12 from milk is more
      efficiently absorbed than the synthetic form used in vitamin supplements. Pigs (n
      10) were used as a model for intestinal absorption of vitamin B12 in humans to
      compare the net fluxes of vitamin B12 across the portal-drained viscera (PDV; an
      indicator of intestinal absorption) after ingestion of meals complemented with
      conventional and vitamin B12-enriched (via injections to cows) milk (raw,
      pasteurised or microfiltrated) or with equivalent amounts of cyanocobalamin, the
      synthetic form used in supplements or unsupplemented. Net flux of vitamin B12
      across PDV after the ingestion of milk was positive, though not influenced by
      milk enrichment (P>0.3) or technological processes (P = 0.8) and was greater than
      after ingestion of equivalent amounts of cyanocobalamin (cyanocobalamin v. all
      milk, P <= 0.003). In fact, net fluxes of this vitamin were not different from 0
      after either cyanocobalamin or the meal devoid of vitamin B12 (unsupplemented v.
      cyanocobalamin, P = 0.7). The cumulative PDV fluxes during the 24 h following
      ingestion of meals complemented with milk varied from 5.5 to 6.8 MUg. These
      values correspond to an efficiency of intestinal absorption of vitamin B12 from
      milk varying between 8 and 10 %. Therefore, vitamin B12, which is abundant in
      cows' milk, is also substantially more available than the most commonly used
      synthetic form of this vitamin.

PMID- 21733331
TI  - Different variations of tissue B-group vitamin concentrations in short- and long
      term starved rats.
AB  - Prolonged starvation changes energy metabolism; therefore, the metabolic response
      to starvation is divided into three phases according to changes in glucose, lipid
      and protein utilisation. B-group vitamins are involved in energy metabolism via
      metabolism of carbohydrates, fatty acids and amino acids. To determine how
      changes in energy metabolism alter B-group vitamin concentrations during
      starvation, we measured the concentration of eight kinds of B-group vitamins
      daily in rat blood, urine and in nine tissues including cerebrum, heart, lung,
      stomach, kidney, liver, spleen, testis and skeletal muscle during 8 d of
      starvation. Vitamin B1, vitamin B6, pantothenic acid, folate and biotin
      concentrations in the blood reduced after 6 or 8 d of starvation, and other
      vitamins did not change. Urinary excretion was decreased during starvation for
      all B-group vitamins except pantothenic acid and biotin. Less variation in B
      group vitamin concentrations was found in the cerebrum and spleen. Concentrations
      of vitamin B1, vitamin B6, nicotinamide and pantothenic acid increased in the
      liver. The skeletal muscle and stomach showed reduced concentrations of five
      vitamins including vitamin B1, vitamin B2, vitamin B6, pantothenic acid and
      folate. Concentrations of two or three vitamins decreased in the kidney, testis
      and heart, and these changes showed different patterns in each tissue and for
      each vitamin. The concentration of pantothenic acid rapidly decreased in the
      heart, stomach, kidney and testis, whereas concentrations of nicotinamide were
      stable in all tissues except the liver. Different variations in B-group vitamin
      concentrations in the tissues of starved rats were found. The present findings
      will lead to a suitable supplementation of vitamins for the prevention of the re
      feeding syndrome.

PMID- 21733332
TI  - Acute satiety response of mammalian, avian and fish proteins in dogs.
AB  - Fish proteins have been reported to be more satiating than meat proteins. The
      objective was to determine the effect of different animal protein pre-meals on
      satiety. A total of ten intact female hounds were fed pork loin, beef loin,
      chicken breast, salmon fillet or pollock fillet. Each pre-meal was fed to contain
      100 g protein. Blood was collected at 0, 5, 15, 30, 60, 90 and 120 min
      postprandially and analysed for glucose, insulin, total ghrelin, active glucagon
      like peptide-1 (GLP-1) and plasma amino acids (AA). Dogs were fed 2 * 
      metabolisable energy, 3 h following the pre-meal, and intake was determined 30,
      60, 180 and 1440 min after food presentation. Glucose decreased over time (P <
      0.001), but was lowest (P = 0.01) when dogs consumed pollock or chicken. Insulin
      increased (P < 0.0001) over time, and was greater (P = 0.09) when dogs consumed
      salmon. GLP-1 increased (P < 0.001) over time, and was greatest (P = 0.04) when
      dogs consumed beef. Ghrelin decreased (P < 0.0001) over time for all pre-meals.
      The tryptophan:large neutral AA ratio tended to be greater (P = 0.08) when dogs
      consumed pork, salmon and pollock. Different protein sources may influence blood
      markers in dogs, but it does not appear that fish substrates have different
      satiating abilities than mammalian or avian sources.

PMID- 21733333
TI  - Dietary free glutamate prevents diarrhoea during intra-gastric tube feeding in a
      rat model.
AB  - Recent studies indicate that l-glutamate (l-Glu), abundant in many foods, is a
      stimulator of gastric vagal afferent nerves. The aim of the present study was to
      examine the possibility that l-Glu supplementation of a protein-rich liquid diet
      may prevent the incidence of diarrhoea during repetitive intra-gastric tube
      feeding. The gastric vagal afferent nerve recording of rats indicated that intra
      gastric administration of a protein-rich liquid diet supplemented with 0.5 %
      monosodium glutamate enhanced the basal afferent activities seen with the protein
      rich diet alone. The examination of the faeces showed that the addition of
      monosodium glutamate to the liquid diet significantly prevented the incidence of
      diarrhoea induced by repetitive gastric feeding. In conclusion, supplementation
      of an enteral liquid diet with free l-Glu may ameliorate diarrhoea during intra
      gastric tube feeding by sending visceral glutamate information from the stomach
      to the brain.

PMID- 21733334
TI  - Blood profiling of proteins and steroids during weight maintenance with
      manipulation of dietary protein level and glycaemic index.
AB  - Weight regain after weight loss is common. In the Diogenes dietary intervention
      study, a high-protein and low-glycaemic index (GI) diet improved weight
      maintenance. The objective of the present study was to identify (1) blood
      profiles associated with continued weight loss and weight regain (2) blood
      biomarkers of dietary protein and GI levels during the weight-maintenance phase.
      Blood samples were collected at baseline, after 8 weeks of low-energy diet
      induced weight loss and after a 6-month dietary intervention period from female
      continued weight losers (n 48) and weight regainers (n 48), evenly selected from
      four dietary groups that varied in protein and GI levels. The blood
      concentrations of twenty-nine proteins and three steroid hormones were measured.
      The changes in analytes during weight maintenance largely correlated negatively
      with the changes during weight loss, with some differences between continued
      weight losers and weight regainers. Increases in leptin (LEP) and C-reactive
      protein (CRP) were significantly associated with weight regain (P < 0.001 and P =
      0.005, respectively), and these relationships were influenced by the diet.
      Consuming a high-protein and high-GI diet dissociated the positive relationship
      between the change in LEP concentration and weight regain. CRP increased during
      the weight-maintenance period only in weight regainers with a high-protein diet
      (P < 0.001). In addition, testosterone, luteinising hormone, angiotensinogen,
      plasminogen activator inhibitor-1, resistin, retinol-binding protein 4, insulin,
      glucagon, haptoglobin and growth hormone were also affected by the dietary
      intervention. The blood profile reflects not only the weight change during the
      maintenance period, but also the macronutrient composition of the dietary
      intervention, especially the protein level.

PMID- 21733335
TI  - Mitogen-activated protein kinase mediates the apoptosis of highly metastatic
      human non-small cell lung cancer cells induced by isothiocyanates.
AB  - Dietary isothiocyanates have been shown to possess anti-tumour activity,
      inhibiting several types of cultured human cancer cell growth. However, there are
      limited studies on their effects on cancer cell metastasis. Our previous study
      showed that benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC)
      suppressed human lung cancer cell metastasis potential. In the present study, we
      found BITC (7.5 and 10 MUm) and PEITC (12.5 and 20 MUm) induced highly metastatic
      human non-small cell lung cancer L9981 cell apoptosis in a dose-dependent manner.
      Caspase-3 was activated. They also caused cell cycle arrest at the G2/M phase,
      via modulation of cyclin B1 expression. The mitogen-activated protein kinase
      (MAPK) signalling pathway was involved. c-Jun N-terminal kinase, extracellular
      signal-regulated protein kinase 1/2 and p38 were activated in a dose-dependent
      manner; activator protein 1 (AP-1) transcriptional activation and cyclin D1
      expression were repressed. Apoptosis and MAPK activation were abrogated by anti
      oxidant N-acetyl cysteine (NAC), suggesting that cell death signalling was
      triggered by oxidative stress. Further microarray analysis evaluated the
      potential targeted genes related to apoptosis and the cell cycle. Our studies
      suggested that BITC and PEITC suppressed the metastasis potential of highly
      metastatic lung cancer cells by inducing apoptosis and cell cycle arrest, via
      targeting the MAPK/AP-1 pathway. This may provide a novel approach for metastasis
      therapy of lung cancer by dietary isothiocyanates and possibly other types of
      cancer.

PMID- 21733336
TI  - Chronic caffeine intake decreases circulating catecholamines and prevents diet
      induced insulin resistance and hypertension in rats.
AB  - We tested the hypothesis that long-term caffeine intake prevents the development
      of insulin resistance and hypertension in two pathological animal models: the
      high-fat (HF) and the high-sucrose (HSu) diet rat. We used six groups of animals:
      control; caffeine-treated (Caff; 1 g/l in drinking water during 15 d); HF;
      caffeine-treated HF (HFCaff); HSu; caffeine-treated HSu (HSuCaff). Insulin
      sensitivity was assessed using the insulin tolerance test. Blood pressure, weight
      gain, visceral fat, hepatic glutathione, plasma caffeine, insulin and NO, and
      serum NEFA and catecholamines were measured. Caffeine reversed insulin resistance
      and hypertension induced by both the HF and HSu diets. In the HF-fed animals
      caffeine treatment restored fasting insulin levels to control values and reversed
      increased weight gain and visceral fat mass. In the HSu group, caffeine reversed
      fasting hyperglycaemia and restored NEFA to control values. There were no changes
      either in plasma NO or in hepatic glutathione levels. In contrast, caffeine
      totally prevented the increase in serum catecholamines induced by HF and HSu
      diets. To test the hypothesis that inhibition of the sympathetic nervous system
      prevents the development of diet-induced insulin resistance we administered
      carvedilol, an antagonist of beta1, beta2 and also alpha1 adrenoceptors, to HF
      and HSu rats. Carvedilol treatment fully prevented diet-induced insulin
      resistance and hypertension, mimicking the effect of caffeine. We concluded that
      long-term caffeine intake prevented the development of insulin resistance and
      hypertension in HF and HSu models and that this effect was related to a decrease
      in circulating catecholamines.

PMID- 21733337
TI  - Effect of anthocyanins on expression of matrix metalloproteinase-2 in naproxen
      induced gastric ulcers.
AB  - Non-steroidal anti-inflammatory drugs cause gastric ulceration through a number
      of mechanisms including inhibition of PG synthesis, generation of reactive oxygen
      species (ROS) and induction of apoptosis. Recently, matrix metalloproteinases
      (MMP) have been suggested to play a crucial role in these mechanisms. The present
      study investigated the protective effect of anthocyanins isolated from black rice
      bran (Heugjinjubyeo) against naproxen-induced gastric mucosal injury in rats. The
      oral administration of anthocyanins (5, 25 or 50 mg/kg body weight) showed
      significant protection against naproxen (80 mg/kg body weight)-induced gastric
      ulcer and inhibited lipid peroxidation in the gastric mucosa. In addition,
      pretreatment with anthocyanins resulted in a significant increase in the
      activities of radical-scavenging enzymes such as superoxide dismutase, catalase
      and glutathione peroxidase. Also biochemical and zymographic analyses suggested
      that the administration of anthocyanins gives a significant protection against
      naproxen-induced gastric antral ulcer through scavenging ROS and regulation of
      matrix metalloproteinase-2 (MMP-2) activity. The results of intracellular radical
      activation show that anthocyanins suppress the generation of intracellular ROS
      and attenuate the suppression of MMP-2 activity by naproxen. These results
      suggest that anthocyanins extracted from black rice may offer potential remedy of
      gastric antral ulceration.

PMID- 21733338
TI  - A potential role for CD25+ regulatory T-cells in the protection against casein
      allergy by dietary non-digestible carbohydrates.
AB  - Dietary non-digestible carbohydrates reduce the development of cows' milk allergy
      in mice. In the present study, the contribution of CD25+ regulatory T-cells
      (Treg) was investigated using in vivo Treg depletion and adoptive transfer
      studies. Mice were orally sensitised with casein and fed a diet containing 2 %
      short-chain galacto-, long-chain fructo- and acidic oligosaccharides (GFA) or a
      control diet. Donor splenocytes of mice sensitised with casein and fed the GFA or
      control diet were adoptively transferred to naive recipient mice, which were
      casein- or sham-sensitised and fed the control diet. In addition, in vivo or ex
      vivo CD25+ Treg depletion was performed using anti-CD25 (PC61). The acute
      allergic skin response upon intradermal casein challenge and casein-specific Ig
      were determined. Furthermore, T-helper (TH) 1 and TH2 cell numbers were analysed
      in the mesenteric lymph nodes. The oligosaccharide diet strongly reduced the
      development of the acute allergic skin response, which was abrogated by the in
      vivo anti-CD25 treatment. The diet enhanced the percentage of TH1 cells and
      tended to reduce the percentage of TH2 cells in casein-sensitised mice. Recipient
      mice were protected against the development of an acute allergic skin response
      when transferred with splenocytes from casein-sensitised GFA-fed donor mice
      before sensitisation. Ex vivo depletion of CD25+ Treg abrogated this transfer of
      tolerance. Splenocytes from sham-sensitised GFA-fed donor mice did not suppress
      the allergic response in recipient mice. In conclusion, CD25+ Treg contribute to
      the suppression of the allergic effector response in casein-sensitised mice
      induced by dietary intervention with non-digestible carbohydrates.

PMID- 21733339
TI  - SNP and mRNA expression for glutathione peroxidase 4 in Kashin-Beck disease.
AB  - Kashin-Beck disease (KBD) is a chronic endemic osteoarthropathy, which mainly
      occurs in West and Northeast China. Epidemiological studies suggest that Se
      deficiency is an important environmental factor for the incidence of KBD.
      Glutathione peroxidase 4 (GPx4) belongs to the glutathione peroxidase family,
      which is crucial for optimal antioxidant defences. Our purpose is to investigate
      the putative association between GPx4 polymorphisms and the risk of KBD.
      Restriction fragment length polymorphism-PCR was used to detect two SNP
      (rs713041, rs4807542) in 219 cases and 194 controls in Han Chinese subjects, and
      quantitative analysis for the GPx4 mRNA level was performed by the real-time PCR
      method. The results revealed that linkage disequilibrium existed in the two SNP.
      A significant difference was observed in the haplotype A-T (P = 0.0066) of GPx4,
      which was obviously lower in the KBD cases (0.006 v. 0.032 %). Correlation
      analysis based on a single locus showed no association between each SNP and KBD
      risk. Furthermore, the GPx4 mRNA level was dramatically lower in the blood of KBD
      patients. Overall, our finding indicated GPx4 polymorphisms and decreased mRNA
      level may be related to the development of KBD in the Chinese population,
      suggesting GPx4 as a possible candidate susceptibility gene for KBD.

PMID- 21733340
TI  - Physical activity and obesity in children with congenital cardiac disease.
AB  - BACKGROUND: Children with congenital cardiac disease experience challenges in
      developing healthy patterns of physical activity due to decreased exercise
      capacity and parental fear and confusion about what is permissible. The purpose
      of this study was to describe physical activity habits in children 10-14 years of
      age with congenital cardiac disease and the relationship of those habits to
      obesity as defined by body mass index. METHODS: This cross-sectional study used
      self-report measures and clinical data to describe the association between
      physical activity participation and body mass index in 10- to 14-year-old
      children with congenital cardiac disease. Further, physical activity levels were
      compared between children who were overweight or obese and those who were not.
      RESULTS: Children (n = 84; 51 males; 33 females) reported low rates of physical
      activity compared to reports on healthy children. Only 9.5% were overweight (body
      mass index between the 85th and 94th percentile), and alarmingly 26% were obese
      (body mass index at or above the 95th percentile). Physical activity and body
      mass index were not significantly correlated (r = -0.11, p = 0.45) and there was
      no significant difference in mean physical activity (t = 0.67) between children
      who were overweight or obese and those who were not. CONCLUSIONS: Children in
      this study reported low rates of physical activity and a higher obesity rate than
      was reported in previous studies. However, the two were not significantly
      correlated. Further research is indicated to determine the specific factors
      contributing to obesity and to test interventions to combat obesity in children
      with congenital cardiac disease.

PMID- 21733341
TI  - Single coronary artery giving rise to an intraseptal left coronary artery in a
      patient presenting with neurocardiogenic syncope.
AB  - BACKGROUND: Syncope occurs frequently in adolescents, and is often benign.
      Potential worrisome syncopal events include those occurring with exertion,
      concurrent chest pain, dyspnoea or palpitations, and those with focal or diffuse
      neurologic changes. CASE: A 16-year-old female was referred to our institution
      for a history of exercise-induced spells. She was diagnosed since the age of 2
      years with neurocardiogenic syncope and postural orthostatic tachycardia
      syndrome. She had been evaluated at multiple institutions, and was followed by
      pediatric neurology for a diagnosis of migraines. Owing to recurrent worsening
      symptoms and a syncopal episode requiring resuscitation, an echocardiogram was
      performed. The right coronary was normal, but the left coronary artery ostium
      could not be identified well. Doppler patterns were suspicious of an abnormal
      left coronary artery, and computed tomography angiography was performed. This
      revealed a single coronary artery arising from the right aortic sinus, with the
      left coronary artery arising from the proximal coronary trunk and coursing
      through the infundibular septum. This was surgically treated utilising a left
      internal mammary artery bypass graft to the left anterior descending coronary
      artery. A year later, she has not experienced any recurrence of syncope, and has
      returned to athletic activity. CONCLUSION: This case highlights the index of
      suspicion that must be present when evaluating any patient with syncope, both
      clinically and via echocardiography. A computed tomography angiogram is indicated
      for better evaluation of coronary artery anatomy when an anomalous coronary
      cannot be ruled out by echocardiography.

PMID- 21733342
TI  - Danon disease: characteristic late gadolinium enhancement pattern on cardiac
      magnetic resonance imaging.
AB  - Danon disease is a rare entity associated with the clinical triad of mental
      retardation, skeletal myopathy, and severe hypertrophic cardiomyopathy. We report
      two cases of Danon disease and describe the results of the cardiac magnetic
      resonance imaging studies that were conducted to assess the pattern of cardiac
      hypertrophy.

PMID- 21733343
TI  - Comparison of right ventricular deformation and dyssynchrony in patients with
      different subtypes of hypoplastic left heart syndrome after Fontan surgery using
      two-dimensional speckle tracking.
AB  - BACKGROUND: The left ventricle in patients with hypoplastic left heart syndrome
      may influence right ventricular function and outcome. We aimed to investigate
      differences in right ventricular deformation and intraventricular dyssynchrony
      between hypoplastic left heart syndrome patients with different anatomical
      subtypes and left ventricle sizes after Fontan surgery using two-dimensional
      speckle tracking. PATIENTS AND METHODS: We examined 29 hypoplastic left heart
      syndrome patients aged 5.4 plus or minus 2.8 years after Fontan surgery and
      compared 15 patients with mitral and aortic atresia with the remaining 14
      patients with other anatomic subtypes. We used two-dimensional speckle tracking
      to measure the global and regional systolic longitudinal strain and strain rate
      as well as intraventricular dyssynchrony. RESULTS: Global strain (-19.5, 2.8%
      versus -17.4, 3.9%) and global strain rate (-1.0, 0.2 per second versus -0.9, 0.3
      per second) were not different between groups. The mitral and aortic atresia
      group had higher strain in the basal septal (-13.0, 5.0% versus -3.9, 9.3%, p =
      0.003) and mid-septal (-19.4, 4.7% versus -13.2, 6.5%, p = 0.009) segments, and
      higher strain rates in the mid-septal segment (-1.14, 0.3 per second versus 
      0.95, 0.4 per second, p = 0.047), smaller left ventricle area (0.18, 0.41 square
      centimetre versus 2.83, 2.07 square centimetre, p = 0.0001), and shorter wall-to
      wall delay (38, 29 milliseconds versus 81, 57 milliseconds, p = 0.02).
      CONCLUSION: Significant differences in regional deformation and intraventricular
      dyssynchrony exist between the mitral and aortic atresia subtype with small left
      ventricles and the other anatomic subtypes with larger left ventricles after
      Fontan surgery.

PMID- 21733344
TI  - Results of early foetal echocardiography and cumulative detection rate of
      congenital heart disease.
AB  - OBJECTIVE: The aim of this study is to evaluate the cumulative detection rate of
      foetal echocardiography during gestation and in the early neonatal period, with a
      special emphasis on early foetal echocardiography. METHODS: We conducted a
      retrospective survey of all singleton pregnancies from 1993 to 2007, with
      complete sequential echocardiography from 11 plus 0 to 13 plus 6 weeks of
      gestation. It was mandatory to have at least one foetal echocardiography in the
      second or third trimester and one postnatally. RESULTS: Our study included 3521
      pregnancies, in which 77 cases were diagnosed with congenital heart disease. Of
      them, 66 were detected in the first trimester - 11 plus 0 to 11 plus 6 weeks: 22
      cases; 12 plus 0 to 12 plus 6 weeks: 23 cases; 13 plus 0 to 13 plus 6 weeks: 21
      cases - with an 85.7% detection rate of congenital heart disease in early foetal
      echocardiography. In the second trimester, seven cases were found, with a
      detection rate of 9.1%. The third trimester reported two cases, with a detection
      rate of 2.6%. Postnatally, two (2.6%) cases were detected. The overall in utero
      detection rate of congenital heart disease was 97.4%. CONCLUSIONS: Foetal
      echocardiography performed at the time of anomaly screening in the first
      trimester results in high detection rates of congenital heart disease. Cardiac
      pathology may evolve, and further examinations at later stages of pregnancy could
      improve the detection rate of congenital heart disease.

PMID- 21733345
TI  - Non-communicable diseases--finally on the global agenda.
AB  - After the UN Millennium Development Goals were declared in September 2000 (see
      Table 1), one of the major short-comings recognized world-wide was the lack of
      mention of non-communicable diseases (NCDs). While AIDS and malaria were
      included, none of the leading and universal non-communicable causes of death made
      the list. There was no mention of cardiovascular diseases, cancer or diabetes,
      even though these place a far greater burden on global health and economic
      development than the infectious diseases, and are predicted to continue to
      increase in epidemic proportions. After much public discussion and intense
      lobbying, a significant-and uncommon-achievement occurred: on May 13th, 2010, the
      United Nations General Assembly voted in favour of convening a summit on non
      communicable diseases, to take place in September 2011.

PMID- 21733346
TI  - Patterns of fatal machine rollovers in Canadian agriculture.
AB  - INTRODUCTION: Our objectives were to examine the activities and circumstances
      associated with agricultural machine-related rollover fatalities. METHODS: We
      identified agricultural machine rollover fatalities recorded by the Canadian
      Agricultural Injury Surveillance Program (CAISP) in 1990-2005. We determined
      sideways and backwards rollovers by year, age and sex of the victims,
      agricultural season, machine type, and the activity, circumstances and location
      of the injury event. RESULTS: The annual rate of rollover fatalities in Canada
      was 9.1 per 100,000 farm operations. Rollover fatalities decreased to 30% of
      baseline over the 16-year study period (p = .004). Fatal rollovers most often
      occurred among men aged 50-69 years and 60-79 years for sideways and backwards
      rollovers, respectively. DISCUSSION: Sideways rollovers occur when driving across
      an incline or at the edge of a ditch bordering a roadway or field. Backwards
      rollovers occur when driving up an incline, towing or extracting stuck machines,
      pulling stumps or trees, and towing implements or logs. Primary prevention
      programs for rollover injuries should target these identified patterns of injury.

PMID- 21733347
TI  - Estimating gestational age at birth: a population-based derivation-validation
      study.
AB  - INTRODUCTION: Information on newborn gestational age (GA) is essential in
      research on perinatal and infant health, but it is not always available from
      administrative databases. We developed and validated a GA prediction model for
      singleton births for use in epidemiological studies. METHODS: Derivation of
      estimated GA was calculated based on 130 328 newborn infants born in Ontario
      hospitals between 2007 and 2009, using linear regression analysis, with several
      infant and maternal characteristics as the predictor (independent) variables. The
      model was validated in a separate sample of 130 329 newborns. RESULTS: The
      discriminative ability of the linear model based on infant birth weight and sex
      was reasonably approximate for infants born before the 37th week of gestation (r2
      = 0.67; 95% CI: 0.65-0.68), but not for term births (37-42 weeks; r2 = 0.12; 95%
      CI: 0.12-0.13). Adding other infant and maternal characteristics did not improve
      the model discrimination. CONCLUSION: Newborn gestational age before 37 weeks can
      be reasonably approximated using locally available data on birth weight and sex.

PMID- 21733348
TI  - The influence of primary health care organizational models on patients'
      experience of care in different chronic disease situations.
AB  - OBJECTIVES: To examine the extent to which experience of care varies across
      chronic diseases, and to analyze the relationship of primary health care (PHC)
      organizational models with the experience of care reported by patients in
      different chronic disease situations. METHODS: We linked a population survey and
      a PHC organizational survey conducted in two regions of Quebec. We identified
      five groups of chronic diseases and contrasted these with a no-chronic-disease
      group. RESULTS: Accessibility of care is low for all chronic conditions and shows
      little variation across diseases. The contact and the coordination-integrated
      models are the most accessible, whereas the single-provider model is the least.
      Process and outcome indices of care experience are much higher than accessibility
      for all conditions and vary across diseases, with the highest being for
      cardiovascular-risk-factors and the lowest for respiratory diseases (for people
      aged 44 and under). However, as we move from risk factors to more severe chronic
      conditions, the coordination-integrated and community models are more likely to
      generate better process of care, highlighting the greater potential of these two
      models to meet the needs of more severely chronically ill individuals within the
      Canadian health care system.

PMID- 21733349
TI  - An assessment of the barriers to accessing food among food-insecure people in
      Cobourg, Ontario.
AB  - INTRODUCTION: Low-income people are most vulnerable to food insecurity; many turn
      to community and/or charitable food programs to receive free or low-cost food.
      This needs assessment aims to collect information on the barriers to accessing
      food programs, the opportunities for improving food access, the barriers to
      eating fresh vegetables and fruit, and the opportunities to increasing their
      consumption among food-insecure people in Cobourg, Ontario. METHODS: We
      interviewed food program clients using structured individual interviews
      consisting of mostly opened-ended questions. RESULTS: Food program clients
      identified barriers to using food programs as lack of transportation and the food
      programs having insufficient quantities of food or inconvenient operating hours.
      They also stated a lack of available vegetables and fruit at home, and income as
      barriers to eating more vegetables and fruit, but suggested a local fresh fruit
      and vegetable bulk-buying program called "Good Food Box" and community gardens as
      opportunities to help increase their vegetable and fruit intake. DISCUSSION: Many
      of the barriers and opportunities identified can be addressed by working with
      community partners to help low-income individuals become more food secure.

PMID- 21733350
TI  - Estimates of the treated prevalence of bipolar disorders by mental health
      services in the general population: comparison of results from administrative and
      health survey data.
AB  - INTRODUCTION: Informed provision of population mental health services requires
      accurate estimates of disease burden. METHODS: We estimated the treated
      prevalence of bipolar disorders by mental health services in the Calgary Zone, a
      catchment area in Alberta with a population of over one million. Administrative
      data in a central repository provides information of mental health care contacts
      for about 95% of publically funded mental health services. We compared this
      treated prevalence against self-reported data in the 2002 Canadian Community
      Health Survey: Mental Health and Well-Being (CCHS 1.2). RESULTS: Of the 63 016
      individuals aged 18 years plus treated in the Calgary Zone in 2002-2008, 3659
      (5.81%) and 1065 (1.70%) were diagnosed with bipolar I and bipolar II disorder,
      respectively. The estimated treated population prevalence of these disorders was
      0.41% and 0.12%, respectively. We estimated that 0.44% to 1.17% of the Canadian
      population was being treated by psychiatrists for bipolar I disorder from CCHS
      1.2. DISCUSSION: For bipolar I disorder the estimate based on local
      administrative data is close to the lower end of the health survey range. The
      degree of agreement in our estimates reinforces the utility of administrative
      data repositories in the surveillance of chronic mental disorders.

PMID- 21733351
TI  - Life with arthritis in Canada: a personal and public health challenge.
AB  - "Arthritis" describes more than 100 conditions that affect the joints, the
      tissues that surround joints and other connective tissue. These conditions range
      from relatively mild forms of tendonitis and bursitis to systemic illnesses, such
      as rheumatoid arthritis. Life with arthritis in Canada: a personal and public
      health challenge presents the latest knowledge about arthritis in the Canadian
      population and its wide-ranging impact. It provides an overview of the impact of
      arthritis, and is designed to increase public awareness of the importance of
      prevention and timely management. Although progress has been made on
      interventions, arthritis remains common, disabling and costly. Increasing
      participation in physical activity and maintaining a healthy body weight may help
      to mitigate the effects of arthritis.

PMID- 21733352
TI  - Direct activation of Bmi1 by Twist1: implications in cancer stemness, epithelial
      mesenchymal transition, and clinical significance.
AB  - Cancer stemness is a concept used to describe a minor population of cells (cancer
      stem cells-CSCs) residing in a tumor, which possess self-renewal properties and
      are resistant to chemo/radiation therapy. Epithelial-mesenchymal transition
      (EMT), a major mechanism of cancer metastasis, is a process which generates cells
      with stem-like properties. The relationship between cancer stemness and EMT is
      well documented but without detailed mechanistic explanation. Bmi1 belongs to the
      polycomb repressive complex 1 (PRC1) which maintains self-renewal and stemness.
      Recent results showed that Twist1, an EMT regulator, directly activates Bmi1 and
      these two molecules function together to mediate cancer stemness and EMT. These
      results provide a molecular explanation of the relationship between cancer
      stemness and EMT. Bmi1 is frequently overexpressed in various types of human
      cancers and can confer drug resistance. Twist1 is also overexpressed in various
      human cancers with prognostic significance. The functional interdependence
      between Twist1 and Bmi1 provides a fresh insight into the molecular mechanism of
      EMT-induced cancer stemness. Further investigation of the mechanisms mediating
      EMT and cancer stemness will be helpful in the management and treatment of
      metastatic cancers.

PMID- 21733353
TI  - Arthroscopy- assisted surgery for tibial plateau fractures.
AB  - Like other intra-articular fractures, the tibial plateau fracture is challenging
      for orthopedic surgeons because of its severity of trauma, associated soft tissue
      injuries. Open reduction incurs serious complications, especially wound healing
      after traditional dissections. Unsatisfactory results often occur in complex or
      bicondylar tibial plateau fractures. Traditional surgical methods achieved
      satisfactory results in 70-80% of cases. However, these methods have a high
      incidence of complications including loss of reduction, infection, and septic
      arthritis. The advantages of arthroscopy-assisted reduction and internal fixation
      include direct visualization of intra-articular fracture, accurate fracture
      reduction, and reduced morbidity. It is straightforward in the diagnosis and
      treatment of meniscal and ligamentous injuries, and removal of loose fragments.
      Good early to medium-term results of arthroscopically assisted osteosynthesis of
      tibial plateau fractures have been reported. The author reviews the current
      surgical principles, pitfalls, approaches, clinical results, and complications of
      arthroscopyassisted surgery for tibial plateau fractures.

PMID- 21733354
TI  - Disrupted hepatic adiponectin signaling impairs liver regeneration of steatotic
      rats.
AB  - BACKGROUND: Individuals with non-alcohol fatty liver disease (NAFLD) exhibit
      impaired liver regeneration in a clinical setting and animal experiments.
      Adiponectin signaling is recognized as an important pathway of lipid metabolism,
      energy expenditure, anti-inflammation, and cellular proliferation. We herein
      investigate hepatic adiponectin signaling in dietary steatotic murine models
      undergoing hepatectomy, which has never been explored. METHODS: Sprague-Dawley
      rats fed with a normal diet (normal), high fat diet (HF), and a methionine
      choline deficiency diet for 1 week (MCD 1W) and 5 weeks (MCD 5W), were used. The
      animals underwent 70% hepatectomy and were thereafter sacrificed at indicated
      time points. RESULTS: MCD 5W and HF displayed decreased Ki-67 labeling index and
      restituted liver mass compared to normal. Hepatic adiponectin, as well as TNF
      alpha, of MCD5W and HF were increased compared to normal; whereas adiponectin
      receptor type 1 (AdipoR1) and adiponectin receptor type 2 (AdpoR2) were
      reciprocally decreased when compared to normal. PPARalpha, a downstream molecule
      of AdipoR2 axis, was decreased in MCD 5W compared to normal. Adenosine
      monophosphate- activated protein kinase (AMPK), a downstream molecule of AdipoR1
      axis, was inactivated soon after hepatectomy in normal; whereas activation of
      AMPK persisted until day 3 after hepatectomy in MCD 5W and HF. CONCLUSIONS:
      Reciprocal expression of adiponectin and its receptors in steatotic rats
      represents a unique form of adiponectin signaling disruption, which might be
      associated with impaired liver regeneration.

PMID- 21733355
TI  - Tissue expression of the hepatitis C virus NS3 protein does not correlate with
      histological or clinical features in patients with chronic hepatitis C.
AB  - BACKGROUND: In chronic hepatitis B, the HBcAg viral protein in liver tissue
      demonstrates a positive correlation with serum aminotransferase levels, serum
      hepatitis B viral DNA, and histological activities. Little is known if similar
      relationships exist for chronic hepatitis C. This study attempted to determine if
      expression of the hepatocyte NS3 protein of the hepatitis C virus (HCV-NS3) was
      correlated with the serum HCV-RNA load, hepatitis activity, or other clinical
      parameters. METHODS: Clinical and histological data of 214 patients with chronic
      hepatitis C were retrospectively reviewed. A mouse monoclonal antibody was used
      to detect HCV-NS3 in hepatocytes. The staining intensity was scored
      semiquantitatively as 0~3+, and its correlations with the serum HCV-RNA load,
      hepatitis activity, and other clinical parameters were analyzed. RESULTS: In
      total, 202 (94%) of the 214 liver biopsies were positive for HCV-NS3, and the
      intensity of HCV-NS3 staining was 0 in 12 (6%), 1+ in 181 (84%), and 2+ in 21
      patients (10%). The intensity of HCV-NS3 expression in the samples did not
      correlate with patient age (p = 0.302, ANOVA), patient gender (p = 0.130,
      Fisher's exact test), the alanine transaminase level (p = 0.177, ANOVA), serum
      HCV-RNA level (p = 0.305, ANOVA), HCV antibody titer (p = 0.139, Chi-squared
      test), hepatitis activity index score (p = 0.861, Chisquared test), or sustained
      viral response rate (p = 0.861, Chi-squared test). CONCLUSIONS: This HCV-NS3
      immunohistochemical staining method was reliable for detecting HCV in liver
      specimens. Hepatocyte expression of HCV-NS3 was not correlated with the serum
      viral load, severity of hepatic injury, or treatment response.

PMID- 21733356
TI  - The diagnostic value of computed tomographic coronary angiography in patients
      with acute myocardial infarction versus stable angina pectoris: a preliminary
      report.
AB  - BACKGROUND: Computed tomographic coronary angiography (CTA) is a non-invasive
      alternative to conventional coronary angiography (CCA) in detecting chronic
      coronary artery disease (CAD). However, the value of CTA in estimating acute
      myocardial infarction (AMI) has not been evaluated. METHODS: CTA and CCA were
      performed on 10 patients with non-ST-elevated AMI and 17 patients with stable
      angina pectoris. The plaque components and stenosis severity were assessed by
      both modalities to clarify the diagnostic values of CTA in AMI and stable angina
      pectoris. RESULTS: A high total coronary artery calcium (CAC) score was
      significantly correlated with the presence of CAD and the target lesion CAC score
      (p < 0.01). The AMI group tended to have a lower target CAC score (p = 0.10) and
      target plaque burden (p = 0.27), compared to the stable angina pectoris group. To
      estimate the coronary artery stenotic severity, CTA and CCA had concordant
      correlations in all segments, except in the proximal left anterior descending
      (LAD) artery. The calcium score and calcification fraction percentage in the
      proximal LAD artery were significantly higher than those of other segments (p <
      0.01). Compared to CCA, CTA overestimated the severity of stenosis in the
      proximal LAD arterial segment in the stable angina pectoris group (p = 0.028),
      but not in the AMI group. CONCLUSIONS: CTA has diagnostic values similar to those
      of CCA in detecting coronary lesions in patients with AMI or stable angina
      pectoris. However, a high level of plaque CAC in the stable angina pectoris group
      may lead to an overestimation of the severity of coronary stenosis, especially in
      the proximal LAD arterial segment. Although less remarkable, the impact of CAC on
      the diagnostic value of CTA was still substantial in patients with AMI.

PMID- 21733357
TI  - The levels of stress and depression among interns and clerks in three medical
      centers in Taiwan--a cross-sectional study.
AB  - BACKGROUND: Depression and heavy stress have been reported as two important
      problems for medical students in previous studies; and stress and depression
      levels were also related to gender and grades. The aims of this article were to
      investigate the emotional problems of Taiwanese interns and clerks, and to
      clarify their relationship to work circumstances, identity of interns and clerks
      in the hospitals, gender discrepancy and their levels of stress and depression.
      METHODS: Three medical centers in Taiwan were selected in this study. All interns
      in the three medical centers and clerks in Chang Gung Memorial Hospital were
      invited to complete an anonymous self-report questionnaire. The questionnaire
      included demographic data, levels of various stresses in hospitals recorded with
      visual analog scales, and a Chinese version of Zun's Selfadministered Depression
      Scale. One-way analysis of variance was also adopted to compare the distress
      scores, and the Scheffe test was chosen for the post hoc comparisons. RESULTS:
      First, working in different medical centers was not a factor influencing levels
      of stress and depression of interns. Second, interns had higher stress levels of
      g"work loading" and "occupational risks", and more depressive symptoms, such as
      "poor sleep quality", "poor appetite", "libido loss", "body weight loss", and
      "anhedonia". However, identity did not significantly impact levels of depression.
      Third, gender discrepancy showed significant influences on some stress sources
      and depressed symptoms. CONCLUSIONS: When comparing some depressive symptoms and
      stress sources among medical students, differences of gender and identities were
      statistically significant. Further longitudinal studies are needed.

PMID- 21733358
TI  - Comparison between 0.08% ropivacaine and 0.06% levobupivacaine for epidural
      analgesia during nulliparous labor: a retrospective study in a single center.
AB  - BACKGROUND: Levobupivacaine and ropivacaine are new local anesthetics that have
      effects similar to bupivacaine. However, the relative potency of these two drugs
      is controversial. The purpose of this retrospective study was to assess whether a
      combination of 0.06% levobupivacaine and 0.0002% fentanyl had the same effects as
      0.08% ropivacaine and 0.0002% fentanyl on the mode of delivery and other
      obstetric outcomes when used for epidural analgesia of labor in nulliparous
      women. METHODS: Computer records of 392 Asian nulliparous parturients, who had
      presented with spontaneous labor or spontaneous rupture of the membranes, and had
      received epidural analgesia were retrospectively reviewed. Of these, 193 received
      0.08% ropivacaine and 199 received 0.06% levobupivacaine. Fentanyl (0.0002%) was
      used in both regimens. RESULTS: There were no significant differences in the mode
      of delivery, duration of labor, or neonatal outcome between the two groups. In
      the levobupivacaine group, the parturients required top-up boluses of local
      anesthetics more frequently (1.4 +/- 1.6 vs. 0.9 +/- 1.3, p< 0.0001), and the
      incidence of temporary maternal fever (25 % vs. 15%, p = 0.024) and the cost of
      local anesthetic were higher (292 +/- 183 NTD vs. 146 +/- 104 NTD, p< 0.0001).
      However, the amount of local anesthetic administered during labor was lower (79
      +/- 49 mg vs. 114 +/- 81 mg, p< 0.0001) than for the ropivacaine group.
      CONCLUSIONS: 0.06 % levobupivacaine was as effective as 0.08% ropivacaine, when
      both were used with 0.0002% fentanyl for labor epidural analgesia of nulliparous
      women.

PMID- 21733359
TI  - An anatomical study of the inferior oblique muscle with emphasis on its nerve
      entry.
AB  - BACKGROUND: Anatomical studies regarding the inferior oblique muscle are scarce
      and the exact location of the entry of oculomotor nerve to the muscle has not
      been reported. In the present study, the objectives were to examine the exact
      location of the entry of oculomotor nerve to the inferior oblique muscle and to
      study the topographical anatomy of the muscle. METHODS: The study included 56
      intact orbits from 28 embalmed south Indian adult cadavers. The entire course of
      the nerve to the inferior oblique was exposed from both anterior and posterior
      aspects in all specimens. The exact location of the entry of nerve supplying the
      inferior oblique muscle was identified and the distances of the muscle from
      inferior and medial orbital margins were measured. RESULTS: The oculomotor nerve
      entered the inferior oblique muscle through the orbital surface in 42 (75%)
      cases, through the ocular surface in 10 (17.9%) cases and through the posterior
      border in 4 (7.1%) cases. The distance of the muscle from the inferior orbital
      margin was 1 mm in majority (78.5%) of the cases. The distance of the muscle from
      the medial orbital margin was 11 mm in majority (42.8%) of the cases. CONCLUSION:
      The present study reports that the oculomotor nerve most often enters the
      inferior oblique muscle through its orbital surface. Detailed knowledge of the
      topographical anatomy of inferior oblique muscle and its site of nerve entry are
      essential for surgeons when performing ophthalmological surgery and regional
      anesthesia.

PMID- 21733360
TI  - Clinical results of all-inside meniscal repair using the FasT-Fix meniscal repair
      system.
AB  - BACKGROUND: The meniscus plays a key role in the functioning of the knee. At the
      present time, meniscal repair has becomes the main treatment for meniscal tear.
      Compared to open surgery, arthroscopic meniscal repair has become popular because
      of shorter time need for the operation, the smaller wound, and better
      accessibility to the tear portion, which is particularly difficult during open
      surgery. Three arthroscopic techniques are widely used, namely inside-out,
      outside-in, and all-inside. Arthroscopy all inside meniscal repair has the lowest
      neurovascular injury rate. METHODS: This study prospectively evaluated 31
      consecutively treated patients to determine the effectiveness/safety of
      arthroscopic meniscal repair using the FasTFix repair system. The inclusion
      criteria for this study were: vertical fullthickness tear> 10 mm in length;
      location of the meniscal tear < 6 mm from the meniscocapsular junction; repair of
      the meniscus solely with the FasTFix system; no former meniscus surgery; and no
      evidence of arthritis during arthroscopy. Anterior cruciate ligament (ACL)
      deficient knees were reconstructed using a hamstring autograft at the time of the
      meniscal repair. Follow-up examinations consisted of Lysholm knee score, Tegner
      activity score and radiographic evaluation. RESULTS: After an average of 3 years
      follow-up, no symptoms of meniscal tears were found in 30/31 of the cases. For
      patients with isolated meniscal repair or concurrent ACL reconstruction, the
      Lysholm and Tegner activity scores had significantly improved postoperatively. No
      neurovascular or other major complications were directly associated with the use
      of the device. CONCLUSIONS: Arthroscopic all-inside repair using the FasT-Fix
      device appears to be a safe and effective procedure.

PMID- 21733361
TI  - The characteristics and distribution of dental anomalies in patients with cleft.
AB  - BACKGROUND: Dental anomalies associated with different severities of cleft lip
      and palate have been rarely reported. This retrospective study investigates the
      characteristics of dental anomalies associated with different types of cleft, and
      compares the dental anomaly traits based on sex and severity of cleft. METHODS:
      Cleft patients born in 1995 with qualified diagnostic records from 7 to 11 years
      were included for evaluation. Records were retrieved from database of Chang Gung
      Craniofacial Center, including panoramic radiographs and intraoral photographs.
      In total, 196 patients with complete records were included in the evaluation.
      This study compares the dental anomalies associated with each type of cleft.
      RESULTS: The frequency of dental anomalies in the maxillary incisor area in the
      cleft palate (CP) group (20%) was significantly lower than that in other groups.
      The frequency of missing maxillary lateral incisors (MLIs) increased as the cleft
      severity increased. Supernumerary teeth and missing lower incisors exhibited the
      opposite trend. No sexual dimorphism appeared in terms of the frequencies of peg
      laterals and missing MLIs. The distribution patterns of missing MLIs and peg
      laterals in males, but not in females, were consistent for the three types of
      unilateral clefts. CONCLUSION: Regarding the characteristics of dental anomalies
      among the three unilateral clefts, missing MLIs, supernumerary teeth, and missing
      lower incisors were found to be related to cleft severity. The maxillary lateral
      incisor was the most affected tooth in the cleft area. The frequency of missing
      MLIs and peg laterals was not sexual dimorphic, but the distribution pattern was
      different between the sexes.

PMID- 21733362
TI  - Multiple cerebral aneurysms and brain metastasis from primary cardiac
      myxosarcoma: a case report and literature review.
AB  - Primary neoplasms of the heart are rare. Malignant cardiac myxoma, or so-called
      myxosarcoma, accounts for about 6% of primary malignant cardiac tumors. Cerebral
      metastasis of malignant cardiac myxoma is extremely rare; only three cases have
      been reported and two of them included an autopsy study. The case described
      herein is the first reported brain metastasis combined with multiple cerebral
      aneurysms originating from primary cardiac myxosarcoma. The true incidence of
      cerebral myxomatous aneurysm is unknown and the pathogenesis of myxomatous
      aneurysm formation has not been fully defined. The current hypothesis favors that
      tumor materials from cardiac myxomas embolize into the vasa vasorum of the
      peripheral arteries and subsequently prolifere in the vessel wall. This then
      leads to a weakening of subintimal tissue, such as the internal elastic lamina,
      with subsequent aneurysm formation. The prognosis of cardiac myxosarcoma is very
      poor. Although malignancies most likely develop from the mesenchymal cells, they
      are difficult to treat with any modality (operation, chemotherapy, radiotherapy
      or transplantation) because these tumors have usually undergone extensive spread
      by the time the diagnosis is made.

PMID- 21733363
TI  - Retinal pigment epithelial tear after intravitreous triamcinolone acetonide
      injection for fibrovascular pigment epithelial detachment.
AB  - A 78-year-old woman was diagnosed with fibrovascular pigment epithelial
      detachment (PED) associated with age-related macular degeneration (AMD) affecting
      both eyes. Due to decreased vision in her left eye (20/2000) and disease
      progression, the patient received 4 mg of triamcinolone acetonide (TA) by
      intravitreal injection into her left eye. There were no immediate post-injection
      complications in the left eye. However, one week later, a retinal pigment
      epithelial (RPE) tear, temporal-inferior to the fovea in the left eye, was noted
      and confirmed by fundus photography, fluorescein angiography and optical
      coherence tomography. In contrast, there no similar RPE tear occurred in her
      right eye after treated several times by intravitreous bevacizumab injection. Not
      only anti-vascular endothelium growth factor agents, but also intravitreal TA
      when used to treat AMD with PED, would seem to induce a RPE tear in the absence
      of previous or concurrent adjuvant therapy. Further investigations are required
      to confirm the mechanism by which the RPE tear occurs.

PMID- 21733364
TI  - [Pay more attention to standardizing the diagnosis and treatment of intrahepatic
      cholestasis of pregnancy].

PMID- 21733365
TI  - [Relationship between total bile acid concentration and fetal pulmonary
      surfactant in intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: To explore the relationship between total bile acid (TBA)
      concentration and fetal pulmonary surfactant in intrahepatic cholestasis of
      pregnancy (ICP). METHODS: Fifty five patients with ICP (ICP group) who received
      cesarean section from April 2008 to February 2010 in Second Xiangya Hospital,
      Central South University, were recruited. The general conditions of the neonates
      within 7 days after birth in ICP group were recorded. Those with fetal distress,
      neonatal asphyxia, or neonatal respiratory distress syndrome were referred as
      pathological neonates, others were referred as normal neonates. Over the same
      period, 23 healthy gravidas were recruited as control group. Enzymatic method was
      used to detect the TBA concentrations in maternal blood, cord blood and amniotic
      fluid. ELISA was employed to measure the urfactant protein A (SP-A) concentration
      in cord blood. High performance liquid chromatography system was used to detect
      the concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI),
      lysophosphatidylcholine (LPC), and sphingomyelin (SM) in amniotic fluid. RESULTS:
      (1) The concentrations of TBA in maternal blood, cord blood and amniotic fluid
      were (30.1 +/- 7.9), (9.3 +/- 3.3) and (4.4 +/- 1.5) mmol/L in ICP group, (4.8 +/
      2.2), (4.9 +/- 0.9) and (1.4 +/- 1.1) mmol/L in control group, respectively. The
      differences between the two groups were significant (P < 0.05). (2) The SP-A
      concentration in cord blood in ICP group was (29.5 +/- 6.4) ug/L, significantly
      higher than that in control group, which was (22.6 +/- 7.4) ug/L (P < 0.05). (3)
      There were 20 pathological neonates and 35 normal neonates in ICP group. In
      pathological neonates, the concentrations of TBA and SP-A in cord blood were
      (10.9 +/- 2.2) mmol/L, (37.0 +/- 5.9) ug/L, respectively; and were (8.0 +/- 2.8)
      mmol/L, (26.7 +/- 4.8) ug/L in normal neonates. The differences were significant
      (P < 0.05). (4) There was a positive correlation between TBA concentration in
      cord blood and in maternal blood (r(1) = 0.706, P < 0.05). The TBA concentration
      in cord blood was positively correlated with SP-A concentration as well (r(3) =
      0.494, P < 0.05). (5) The PC and PI concentrations in amniotic fluid were (65.4
      +/- 7.2) mg/L and (3.8 +/- 0.6) mg/L in ICP group, (69.7 +/- 3.7) mg/L and (4.3
      +/- 0.7) mg/L in control group, respectively. The differences were significant (P
      < 0.05). The concentration of LPC in amniotic fluid in ICP group was (4.8 +/-
      0.9) mg/L, significantly higher than that in control group (P < 0.05), which was
      (4.2 +/- 0.6) mg/L. The concentration of SM in amniotic fluid was (3.5 +/- 0.8)
      mg/L in ICP group, (4.0 +/- 0.5) mg/L in control group, with no significant
      difference (P > 0.05). (6)The ratio of PC/LPC in ICP group (14.2 +/- 3.2) was
      significantly lower than that in control group (16.9 +/- 2.5) (P < 0.05). (7)The
      TBA concentration in cord blood was negatively correlated with PC and PI
      concentrations (r(1) = -0.561, r(2) = -0.407, P < 0.05), and had no correlation
      with LPC concentration (r(3) = 0.260, P > 0.05). CONCLUSIONS: (1) The fetal TBA
      concentrations in both cord blood and amniotic fluid of patients with ICP was
      higher than those of healthy gravidas, they were also positively correlated with
      maternal TBA concentration. (2) ICP resulted in the change of fetal pulmonary
      surfactant and this change was associated with TBA concentrations in both cord
      blood and amniotic fluid.

PMID- 21733366
TI  - [Expression and significance of interleukin-18, 12 and tumor necrosis factor
      alpha in intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: To investigate the effect of Interleukin (IL)-18, IL-12 and tumor
      necrosis factor-alpha (TNF-alpha) in hepatic injury in intrahepatic cholestasis
      of pregnancy (ICP). METHODS: Sixty-two cases of ICP patients (ICP group), 30
      cases of normal pregnant women (control group) and 30 cases of hepatitis B (HBV)
      women (hepatitis group) were recruited. Serum IL-18, IL-12 and TNF-alpha were
      examined by ELISA. Serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) were examined by automatic biochemical analysis
      instrument. RESULTS: (1) In hepatitis group, serum concentrations of IL-18, IL-12
      and TNF-alpha were (256 +/- 51) ng/L, (122 +/- 96) ng/L and (207 +/- 3) ng/L;
      serum levels of ALT and AST were (363 +/- 174) U/L and (359 +/- 237) U/L,
      respectively. In ICP group, serum concentrations of IL-18, IL-12 and TNF-alpha
      were (72 +/- 32) ng/L, (42 +/- 28) ng/L and (48 +/- 14) ng/L; serum levels of ALT
      and AST were (201 +/- 128) U/L and (132 +/- 87) U/L, respectively.While in
      control group, serum concentrations of IL-18, IL-12 and TNF-alpha were (43 +/-
      13) ng/L, (10 +/- 3) ng/L and (33 +/- 9) ng/L; serum levels of ALT and AST were
      (13 +/- 4) U/L and (15 +/- 3) U/L, respectively. Serum IL-18, IL-12, TNF-alpha,
      ALT and AST levels in hepatitis group were significantly higher than those in ICP
      group and control group (P < 0.05). Serum IL-18, IL-12, TNF-alpha, ALT and AST
      levels in ICP group were significantly higher than those in control group(P <
      0.05). (2) In severe ICP subgroup, serum concentrations of IL-18, IL-12 and TNF
      alpha were (81 +/- 32) ng/L, (50 +/- 25) ng/L and (50 +/- 14) ng/L; serum levels
      of ALT and AST were (269 +/- 111) U/L and (181 +/- 73) U/L. In mild ICP subgroup,
      serum concentrations of IL-18, IL-12 and TNF-alpha were (48 +/- 18) ng/L, (17 +/-
      4) ng/L and (40 +/- 10) ng/L; serum levels of ALT and AST were (87 +/- 46) U/L
      and (50 +/- 21) U/L, respectively. Serum IL-18, IL-12, TNF-alpha, ALT and AST
      levels in severe ICP subgroup were significantly higher than those in mild ICP
      subgroup and control group (P < 0.05). And serum ALT and AST levels in mild ICP
      subgroup were significantly higher than those in control group (P < 0.05). (3)
      There were 16 cases with preterm birth (50%, 16/32) and 10 cases with meconium
      stained amniotic fluid (31%, 10/32) in severe ICP subgroup, significantly higher
      than those in mild ICP subgroup (P < 0.05), which contained 2 preterm births (7%,
      2/30) and 1 meconium-stained amniotic fluid (3%, 1/30). While in control group,
      the numbers were 1 (3%, 1/30) and 1 (3%, 1/30), respectively. As for the cases of
      neonates whose 1 minute Apgar score were not more than 7, there were 2 cases, 1
      case and 1 case in severe ICP subgroup, mild ICP subgroup and control group,
      respectively, which showed no significant difference (P > 0.05). CONCLUSION:
      Serum IL-18, IL-12 and TNF-alpha may be involved in the process of hepatic injury
      of ICP.

PMID- 21733367
TI  - [Clinical analysis of fetal death cases in intrahepatic cholestasis of
      pregnancy].
AB  - OBJECTIVE: To investigate the clinical features, critical laboratory parameters,
      and fetal monitoring methods in intrahepatic cholestasis of pregnancy (ICP).
      METHODS: A retrospective analysis of 21 cases of ICP suffered with fetal death in
      Women's hospital, School of Medicine, Zhejiang University from January 1999 to
      December 2010 were discussed. RESULTS: (1) The average age of ICP patients
      suffered with fetal death were (30.2 +/- 4.6) years old. Among them, 4 cases were
      older than 35 years, six cases were multipara, one of them suffered stillbirth 2
      year before. Twenty cases were singleton pregnancies and 1 case was twin
      pregnancy. (2) All 21 cases of fetal death occurred in the third trimester, 12
      cases occurred before 37 weeks, 9 cases after 37 weeks.Nine cases were diagnosed
      by ultrasound in outpatient clinics, fetal heart beat disappeared in 9 patients
      after admission because of ICP, two disappeared after labor, one during
      anesthesia before emergent surgery. Perinatal mortality rate of ICP was 0.148%
      (21/14 184), and fetal death occurred from 29 to 41 weeks with an average
      gestational age of (33.8 +/- 4.2) weeks. (3) Puritus occurred in all 21 cases
      while 11 of them had pruritus all over the body. Ten pregnant women felt the
      fetal movement decreased or disappeared before diagnosis of fetal death. The
      glycocholic acid levels increased in all of the 21 cases. Among them, glycocholic
      acid levels in 11 cases were (21.49 - 64.48) umol/L, while in 10 cases were >=
      64.48 umol/L. Serum bile acid levels elevated in 16 cases which had been analyzed
      (the other 5 cases had not been checked), and the highest level reached 270
      umol/L. Serum alanine aminotransferase and aspartate aminotransferase were
      increased in 14 cases. Seven cases had their total bilirubin > 21 umol/L, and 12
      cases had their direct bilirubin levels significantly elevated. Among the 21
      cases of ICP, 15 cases were in severe status, while the other 6 cases were mild.
      (4) Nine patients had no antepartum surveillance since fetal death were diagnosed
      before admission. The results of antepartum surveillance were as follows: 2 cases
      had nonreassuring nonstress test (NST), one had mild "V" type deceleration.
      Absence of diastolic flow in umbilical artery were found in 3 cases, and low
      fetal biophysical score was got in one case. (5) All 21 patients had vaginal
      delivery. Six of them delivered after natural contraction, and the remaining 14
      cases delivered after oral intake of mifepristone and amniotic injection of
      ethacridine, or oxytocin induced labor within 48 hours, only one case delivered
      after additional dinoprostone suppositories. The appearance of fetus, placentas
      and membranes were normal, the lengths of umbilical cord were average. Four cases
      were found with cords binding the necks or the bodies. Eighteen cases had grade
      III amniotic fluid with meconium-stained, and 2 cases complicated by
      oligohydramnios. Ten cases had their fetuses and placentas examined by
      pathologist. Among them, one case had multiple malformations, no more obvious
      pathological abnormalities were found in other fetuses. Pathologic examination
      showed that fibrin deposited around chorion and deciduas basalis, large vessels
      accompanied by calcification, degeneration, hemorrhagic infarction, and increased
      focal syncytial nodules could be seen in all of the ten placentas. CONCLUSIONS:
      Fetal death in pregnant women with ICP often occurs after the contractions,
      Severe ICP may be a key factor that involved in the occurrence of fetal death. Up
      to now, there is no valid indicators in fetal monitoring, which can predict fetal
      death. Extensive assessment of the severity and careful antepartum surveillance
      should be achieved before timely termination of pregnancy.

PMID- 21733368
TI  - [Expression and clinical significance of constitutive androstane receptor in
      placental syntrophoblast of intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: To explore the expression and clinical significance of constitutive
      androstane receptor (CAR) in placenta syntrophoblast from patients with
      intrahepatic cholestasis of pregnancy (ICP). METHODS: Placenta were collected
      from women with ICP who delivered from April 2009 to March 2010 in First
      Affiliated Hospital of Chongqing Medical University. According to the severity of
      ICP, patients were classified into mild ICP group (n = 10) and severe ICP group
      (n = 10). Ten healthy pregnant women who delivered in the same period were chosen
      as control group. The location of CAR protein in placenta was studied by
      immunohistochemical streptavidin-biotin complex (SABC) method. CAR mRNA level was
      determined by reverse transcription (RT)-PCR technique and CAR protein expression
      level was determined by western blot. RESULTS: (1) CAR was located in the
      placenta syncytiotrophoblastic cells in control group and mild ICP group, showed
      light tan when stained, and was mainly in the cytoplasm. In severe ICP group, CAR
      was also located in placenta syncytiotrophoblastic cells but mainly in the
      nucleolus, showed dark tan when stained. (2) The mRNA expressions of CAR in
      control group, mild ICP group, severe ICP group were 0.06 +/- 0.03, 0.07 +/- 0.03
      and 0.56 +/- 0.03, respectively. CAR in severe ICP group was significantly higher
      than those in control group and mild ICP group (P < 0.05). The difference of mRNA
      between control group and mild ICP group was not statistically significant (P >
      0.05). (3) The CAR protein levels in control group, mild ICP group, severe ICP
      group were 0.74 +/- 0.03, 0.79 +/- 0.03 and 1.02 +/- 0.04, respectively. CAR
      protein expression in the severe ICP group was significantly higher than the
      other two groups (P < 0.05). And there was no statistical significance between
      mild group and control group (P > 0.05). CONCLUSION: In ICP women, especially
      severe ICP patients, the CAR expression in placenta syncytiotrophoblastic cells
      increased appreciably, which may be involved in the maintenance of placenta
      barrier function and protection in ICP pathogenesis.

PMID- 21733369
TI  - [Clinical significance of intermittent sinusoidal fetal heart rate at third
      trimester].
AB  - OBJECTIVE: To investigate clinical significance of intermittent sinusoidal fetal
      heart rate at third trimester. METHODS: From Jan 2002 to Dec 2010, 48 pregnant
      women at 33 to 41 gestational weeks undergoing electronic fetal heart rate (FHR)
      monitoring presented with intermittent sinusoidal FHR in Department of Obstetrics
      and Gynecology, Second School of Clinical Medicine, Jinan University were
      enrolled in this retrospective study. Twenty-one cases were categorized into
      continuous group (i.e. with sinusoidal feature and a constant duration >= 10
      minutes), while the other 27 cases were categorized into intermittent group (i.e.
      with a duration < 10 minutes). In the mean time, 76 normal cases were chosen
      randomly matched as control group. Blood gas and hemoglobin were measured in
      umbilical artery after fetal head delivery. General neurological system
      examination were performed in those fetus in hospitalization. The outcome of
      those fetuses was compared. RESULTS: (1) Neonatal complications: the rate of
      asphyxia, meconium-stained amniotic fluid and fetal anemia were 63% (17/27), 33%
      (9/27) and 63% (17/27) in group of intermittent sinusoidal FHR, which were
      significantly higher than 1% (1/76), 4% (3/76), 3% (2/76) in control group (P <
      0.05). When compared with 67% (14/21), 52% (11/21), 76% (16/21) in group of
      continuous sinusoidal, the statistical difference were not observed (P > 0.05).
      (2) Blood gas in neonate: the rates of pH less than 7 were 18% (5/27) in
      intermittent group, 52% (11/21) in continuous group and 0 in control group, which
      all reached statistical difference among those three groups (P < 0.05). (3) Brain
      damage and death: the rates of brain damage and death were 48% (13/27) and 11%
      (3/27) in intermittent group, 81% (17/21) and 43% (9/21) in continuous group, and
      0 in control group, which all showed significant difference between them (P <
      0.05). CONCLUSION: Intermittent and continuous sinusoidal FHR are typical
      graphics of severe fetal anemia at third trimester. Intermittent sinusoidal FHR
      is indicative of serious fetal hypoxia.

PMID- 21733370
TI  - [Evaluation the efficacy and safety of estradiol and drospirenone tablets in the
      treatment of menopausal symptoms among postmenopausal Chinese healthy women:a
      randomized, multi-center, double-blind, placebo-controlled clinical study].
AB  - OBJECTIVE: To study the efficacy and safety of estradiol and drospirenone tablets
      (Angeliq) in treatment of menopausal symptoms among postmenopausal Chinese
      healthy women. METHODS: Total 244 postmenopausal Chinese healthy women who had
      moderate to severe hot flushes were randomly assigned into estradiol and
      drospirenone (observation group, n = 183) or placebo group (n = 61) by the ratio
      of 3:1 for 16 weeks in this randomized multi-center double-blind placebo
      controlled study. During the trial, the follow-up visits were conducted at week
      4, 8, 12, 16 of treatment and 2 weeks after treatment respectively. Height,
      weight, vital signs, hot flushes, other relevant menopausal symptoms and vaginal
      bleeding were observed in each follow-up visit, while the clinical global
      impression scale was assessed at 16 weeks as well. RESULTS: It showed that hot
      flushes were reduced significantly more in observation group than that in placebo
      group (P < 0.01), although both treatments were effective. The absolute values of
      mean severity index of total hot flushes decreased by -0.6 +/- 0.5 in observation
      group and -0.4 +/- 0.4 in placebo group from baseline respectively, which reached
      significant difference (P < 0.05). However, the absolute values of mean severity
      index of moderate to severe hot flushes decreased by -0.6 +/- 0.8 in observation
      group and -0.3 +/- 0.6 in placebo group from baseline respectively, which had no
      significant difference (P > 0.05). After 16 weeks treatment, it also showed that
      estradiol and drospirenone had significant better efficacy than placebo on
      moderate to severe sweating, vaginal dryness and clinical global impression scale
      (P < 0.01). During the trial, blood pressure in observation group was stable. The
      rate of vaginal bleeding in observation group was higher than that in the placebo
      group, especially during the week 4 to week 8 when 48.9% (87/178) in observation
      group and 10.7% (6/56) in placebo group of patients bled. Although the cumulative
      amenorrhea rate of observation group was lower than that of placebo group in each
      cycle (28 days), it increased gradually along with duration of the treatment. The
      commonest adverse event in observation group was breast tenderness which
      accounted for 12.0% (22/183). The level of serum potassium was in the normal
      range in observation group mostly.Meanwhile, the other adverse events rate was
      low. Serious adverse events reported in this trial were assessed as not study
      drug related or as unlikely study drug related. CONCLUSION: Estradiol and
      drospirenone tablets which could effectively alleviate menopausal symptoms in
      postmenopausal Chinese healthy women is a novel hormone replacement therapy
      regimen with high safety and efficacy.

PMID- 21733371
TI  - [Clinical significance of counting follicles in diagnosis of polycystic ovary
      syndrome by the three-dimensional ultrasound imaging with sonography based
      automated volume calculation method].
AB  - OBJECTIVE: To investigate clinical significance of counting follicles
      classification by three-dimensional imaging with sonography based automated
      volume calculation (SonoAVC) in the diagnosis of polycystic ovary syndrome
      (PCOS). METHODS: Eighty cases with PCOS were counted classified follicles and
      determined ovarian volume by three-dimensional (3D) imaging with SonoAVC method
      matched with 60 infertile women with fallopian tube or male factors as control.
      Main clinical, biological and other ultrasonographic markers were assessed during
      the early follicular phase, and the relationship between the follicle number
      range per ovary or the volume per ovary and the major hormonal features of PCOS
      was studied. RESULTS: Three-dimensional ultrasound imaging with SonoAVC method
      provides a new path for objective quantitative assessment of follicle count,
      ovarian volume, total follicle numbers. The volume of (11 +/- 8) ml, total
      numbers of 27 +/- 14 follicle and number of 22 +/- 19 follicle with diameter of
      >= 2 - < 6 mm in PCOS patients were significantly higher than (6 +/- 4) ml in
      ovarian volume, 6 +/- 4 in total follicles and 2 +/- 3 in follicle with diameter
      of >= 2 - < 6 mm in controls (P < 0.05), while follicles were similar for the >=
      6 - <= 9 mm range (P > 0.05). Total follicle numbers and follicles >= 2 - < 6 mm
      had significantly positive relationships with ovarian volume (r = 0.600, 0.618, P
      < 0.01) and level of testosterones (r = 0.364, 0.291, P < 0.05), follicles >= 2 -
      < mm also had significantly positive relationships with total follicle number (r
      = 0.916, P < 0.01). The follicles within the >= 6 - <= 9 mm range was
      significantly and negatively related to ovarian volume and total follicle numbers
      (r = -0.618, -0.263, all P = 0.001), but no significantly related to the major
      hormonal features of PCOS. The ovarian volume was significantly positively
      related with luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio (r
      = 0.282, P = 0.010) but negatively related to FSH level (r = -0.226, P = 0.042).
      CONCLUSIONS: Ovarian volume, total follicle numbers and follicles >= 2 - < 6 mm
      in PCOS patients were significantly higher than those in controls. The larger
      ovarian volume might produce more total follicle and follicles >= 2 - < 6 mm. The
      higher level of testosterone might produce more total follicle probably, which
      mainly result in more follicles >= 2 - < 6 mm. These morphologically
      ultrasonographic characteristics could reflect pathophysiological changes in
      PCOS. Obviously, it has important clinical significance to count follicles in
      patients with PCOS by the three-dimensional ultrasound imaging with SonoAVC
      method.

PMID- 21733372
TI  - [Mechanism of hypoxia inducing factor-1alpha in low endometrial receptivity].
AB  - OBJECTIVE: To study the mechanism of hypoxia inducing factor-1alpha (HIF-1alpha)
      pathway in establishment of hypoxia inducing low endometrial receptivity.
      METHODS: RL95-2 cell lines, the ideal model of study ER, were cultured in hypoxia
      condition induced by CoCl2, and the expression of mRNA and protein of HIF-1alpha
      and tumor necrosis factor like weak inducer of apoptosis (TWEAK) were measured by
      reverse transcription-PCR and western blot. The apoptosis rate was analyzed by
      flow cytometry. Then the mechanism confirmed by comparing the two factors in
      endometrium and the ultra-appearance of inflammatory reaction and apoptosis
      between recurrent spontaneous abortion women and control women. RESULTS: (1) On
      different time point (0, 12, 24, 48 hour), mRNA expression of HIF-1alpha were
      0.272 +/- 0.010, 0.354 +/- 0.020, 0.591 +/- 0.020, 0.890 +/- 0.020, while the
      expression of TWEAK were 0.104 +/- 0.010, 0.510 +/- 0.020, 1.021 +/- 0.020, 1.237
      +/- 0.040, respectively, the expression level between 12, 24, 48 and 0 hour all
      showed significant differences (P < 0.05). (2) Protein expression of HIF-1alpha
      were 0.853 +/- 0.010, 0.931 +/- 0.030, 1.124 +/- 0.010, 1.317 +/- 0.020
      respectively, while was 0.042 +/- 0.010, 0.091 +/- 0.010, 0.131 +/- 0.020, 0.205
      +/- 0.030 in TWEAK expression, the different level were statistically significant
      (P < 0.05). (3) With longer culture under hypoxia, the cell apoptosis rate
      increased obviously. The apoptosis rate of each time point were (3.2 +/- 1.4)%,
      (16.2 +/- 3.2)%, (26.3 +/- 3.5)%, (31.8 +/- 3.5)%, the differences between 12,
      24, 48 and 0 hour had significance (P < 0.05). (4) The positive rate of HIF
      1alpha stained in epithelium cells and stroma cells of test group were 32.3%,
      8.4% and 16.7%, 7.3% in control group. The positive rate of TWEAK were 28.3%,
      3.9% in recurrent spontaneous abortion group and 11.6%, 2.7% in control group (P
      < 0.05). The ultra-appearance of inflammatory cell infiltrated and apoptosis were
      obvious in test group. CONCLUSIONS: Cell inflammation reaction and apoptosis
      induced by HIF-1alpha pathway may participate the mechanism of hypoxia inducing
      low endometrial receptivity. HIF-1alpha might become a novel target for improving
      poor endometrial receptivity.

PMID- 21733373
TI  - [Clinicopathologic analysis of small cell neuroendocrine carcinoma of the
      cervix].
AB  - OBJECTIVE: To analyse the clinico-pathologic characteristics, diagnosis, therapy
      and prognostic of small cell neuroendocrine carcinoma of the cervix (SCNCC).
      METHODS: The clinic-pathological features of 12 patients with SCNCC treated in
      Tumor Hospital of Guangxi Medical University, admitted during March 2006 to July
      2010, were analyzed retrospectively. RESULTS: Of 12 patients, the mean age was
      38.7 years (rang 28 - 57 years), 6 had stages Ib1-IIa, 6 had stages IIb-IV. Among
      8 patients (Ib1-IIIb) underwent surgery, 4 of them received neoadjuvant
      chemotherapy, 8 of them received adjuvant chemotherapy and(or) radiotherapy. All
      had greater than one-half stromal invasion, 4 patients had positive pelvic lymph
      nodes metastases. The positive ratio of the chromogranin (CgA), synaptophysin,
      neuronspecific enolase (NSE), cytokeratins (CK), CD(56) tested by
      immunohistochemical staining were 8/12, 9/10, 4/4, 4/4, 4/4, respectively. Median
      follow-up period was 3 months (1 - 22 months). Among 8 patients underwent
      surgery, 2 patients developed lung metastases, 1 patient developed liver and lung
      metastases, 1 patient developed liver metastases concurrently with bone
      metastases, disease-free survival (DFS) were 3 months (Ib2 with positive lymph
      nodes), 4.6 months (IIa), 7 months (Ib1), 17 months (Ib2); 2 patient died (8.5
      and 11.3 months, respectively) after surgery; 4 patients are alive and show no
      evidence of disease. Among 4 patients untreated, 1 patients received concurrent
      chemoradiation and are alive for 10.1 months. Two patient untreated (IIIb, IV)
      died after 0.6 and 1.3 months final diagnosis, respectively. One patient was lost
      follow-up. CONCLUSIONS: SCNCC is a highly malignant tumor with rare morbility,
      propensity for distant spread and dismal prognosis. Final diagnosis of SCNCC
      depends on pathomorphology and immunohistochemical analysis. Combined therapeutic
      modalities may in favor of survival in some patients.

PMID- 21733374
TI  - [In vivo and in vitro research study of the influence on placenta angiogenesis by
      gene silencing of netrin-1].
AB  - OBJECTIVE: To study influence on angiogenesis of placenta by gene silencing of
      netrin-1. METHODS: Netrin-1 gene in human umbilical vein endothelial cells
      (HUVEC) and placenta of pregnant rats were silenced by RNA interference. The
      following methods were used in this study, including the phenytetrazoliumromide
      (MTT) for viability, clone formation for proliferation, transwell for migration,
      and tube formation for angiogenesis in vitro. The change of fetal growth was
      recorded. Placental microvessel density in pregnant rats was measured by
      immunohistochemical CD(34) staining in vivo. RESULTS: (1) HUVEC: viability and
      proliferation of HUVEC were remarkably inhibited by gene silencing of netrin-1,
      which number of clone formation, migration cell, tube formation were from (69 +/-
      6)%, 86 +/- 17, 37 +/- 9 decreased to (46 +/- 5)%, 46 +/- 13 and 17 +/- 5 (P <
      0.05) respectively. (2) Placenta of pregnant rats: after netrin-1 gene silenced,
      fetal weight were decreased from (2.39 +/- 0.17) g to (2.12 +/- 0.10) g (P <
      0.05). Placental microvessel density was decreased from (258 +/- 38)/mm(2) to
      (197 +/- 32)/mm(2) in vivo (P < 0.05). CONCLUSIONS: Gene silencing of netrin-1
      could inhibit viability, proliferation, migration, tubal formation of HUVEC and
      angiogenesis of placenta. Netrin-1 plays an important role in regulating
      angiogenesis in placenta.

PMID- 21733375
TI  - [Preferred reporting items for systematic reviews and meta-analysis for reporting
      quality of Chinese meta-analysis on stomatology].
AB  - OBJECTIVE: To determine the current status and influence factors of reporting
      quality of the Chinese meta-analysis on stomatology. METHODS: A comprehensive
      electronic search was carried out through Chinese BioMedical Literature Database
      (CBM), VIP Database for Chinese Technical Periodicals (VIP) and China National
      Knowledge Infrastructure (CNKI) and a hand searching was also performed through
      19 stomatological journals in Chinese to identify meta-analysis on stomatology.
      Two reviewers took responsibility for study inclusion, data extraction and
      reporting quality assessment with preferred reporting items for systematic
      reviews and meta-analysis (PRISMA) in duplicate and any disagreement was resolved
      by discussion. RESULTS: A total of 34 meta-analysis on stomatology were eligible,
      most of them were on oral medicine and oral and maxillofacial surgery, and mainly
      focusing on etiology, prevention and treatment of oral diseases. The number of
      the meta-analysis increased during recent years. Reporting quality of the meta
      analysis was not high and the PRISMA scored (13.6 +/- 4.2). The main factors that
      influenced the reporting quality of meta-analysis were published on evidence
      based medicine journals (adjusted beta = 0.53, t = 4.15, P < 0.001) and year of
      publication (adjusted beta = -0.44, t = -3.28, P = 0.001). The sensitivity
      analysis showed that this outcome was stable. CONCLUSIONS: Reporting quality of
      the Chinese meta-analysis on stomatology is low. To provide sufficient evidence
      to the clinicians and promote the development of evidence-based dentistry in
      China, experts on stomatology should study the knowledge of evidence-based
      medicine and comply with PRISMA statement when producing the meta-analysis.

PMID- 21733376
TI  - [Dental anomalies in Chinese children with complete unilateral cleft lip and
      palate].
AB  - OBJECTIVE: To investigate the prevalence of dental anomalies in Chinese children
      with complete unilateral cleft lip and palate (UCLP). METHODS: Dental histories
      and radiographs of 244 Chinese children with UCLP were collected. The diagnosis
      of dental anomalies was based on panoramic radiographs before alveolar bone
      grafting. All patients were over 8 years old. RESULTS: In the UCLP group, 66.8%
      of the patients was presented with hypodontia. The maxillary lateral incisors
      were the most common teeth affected, followed by maxillary second premolars,
      mandibular incisors and mandibular second premolars. A total of 33.6% the
      patients was presented with dental malformation, most were microdontic laterel
      incisors. A total of 4.9% the patients was presented with hyperdontia. The
      supernumerary teeth were more frequently found in the cleft region. The
      prevalence of missing maxillary lateral incisor in the noncleft side was
      statistically different between genders, which was higher in male (P < 0.050).
      This group of Chinese children with UCLP demonstrated significantly higher
      prevalence of hypodontia, hyperdontia, and malformation on the cleft side than on
      the noncleft side (P < 0.01). CONCLUSIONS: Hypodontia is the most common type of
      dental anomalies. The prevalence of dental anomalies is higher in the UCLP
      patients than in the normal population. Dental anomalies occur more frequently on
      the cleft side than on the noncleft side.

PMID- 21733377
TI  - [Preliminary study on genotypic diversity of Streptococcus mutans in Xinjiang
      Uygur preschool children].
AB  - OBJECTIVE: To investigate the relationship between genotypic diversity of
      Streptococcus mutans (Sm) and deciduous teeth caries in Xinjiang Uygur autonomous
      region. METHODS: Isolates of Sm were obtained from 17 caries-free and 17 caries
      active Uygur preschool children aged from 3 to 5 years. A total of 143 isolates
      were subcultured, biochemically characterised and identified by polymerase chain
      reaction (PCR) as Sm and Streptococcus sobrinus (Ss). Then the Sm isolates were
      genotyped by arbitrarily primed-PCR (AP-PCR). RESULTS: A total of 81 Sm isolates
      from caries-active subjects and 62 isolates from caries-free subjects were
      identified by PCR and forty distinct genotypes identified from 143 clinical
      isolates. In seventeen caries-active group, 9 children had only 1 genotype, 5
      children had 2 genotypes, 3 children had 3 genotypes. In seventeen caries-free
      group, 14 children had only 1 genotype, 3 children had more than 2 genotypes. The
      Spearman correlation test showed a strong association between genotypic diversity
      and caries experience (r = 0.342, P < 0.05). CONCLUSIONS: Isolates of Sm in
      caries-active Uygur preschool children show apparent more genetic diversity than
      those in caries-free children. The genotypes of isolates might be related to
      differences in caries susceptibility.

PMID- 21733378
TI  - [Clinical study of osteotome sinus floor elevation without grafting and with
      simultaneous implants placement].
AB  - OBJECTIVE: To investigate the clinical results of osteotome sinus floor elevation
      (OSFE) without grafting combined with simultaneous implant placement. METHODS: A
      total of 65 patients underwent maxillary sinus floor elevation from alveolus
      without any bone grafting from January 2000 to December 2008 and 96 implants were
      placed in the maxillary posterior edentulous region simultaneously. Clinical and
      radiography examinations were performed. The residual bone height ranged from 5
      to 8 mm and the mean bone height was (6.78 +/- 1.04) mm. The mean following
      period was 33.4 months. Statistical analysis was performed by chi square test.
      RESULTS: Ninety-five of 96 implants were clinically stable and functioned without
      any pain and other complaints. One implant was extracted 15 days after operation
      because of mobility and the other implants obtained osseointegration. The mean
      implant protrusion length was 2.6 mm, ranging from 1 to 5 mm. Different degree of
      new bone formation was observed in 51 (54%) of implants. New maxillary sinus
      floor outline was observed in 33 (35%) of implants and there was no obvious new
      bone in 11 (12%) of implants. There was no significant deference between the
      implant protrusion length and sinus floor remodeling. CONCLUSIONS: Under strict
      indications, the clinical results of OSFE without bone grafting combined with
      simultaneous implant placement were predictable in short term. The new sinus
      floor formation was not related to the implant protrusion length.

PMID- 21733379
TI  - [Expression of tumor necrosis factor in placenta tissue of pregnant rats with
      chronic peridontitis].
AB  - OBJECTIVE: To examine the expression of tumor necrosis factor in placenta of
      pregnant rats with chronic periodontitis. METHODS: Twenty Wistar female rats were
      randomly divided into two groups, control (n = 8) and experimental group (n =
      12). The periodontitis model was established in the experimental group. The
      females and males in the two groups got together four weeks later. Nineteen days
      after pregnancy all rats were executed and placenta collected. The delivery time
      and neonatal birth weight were recorded and the pathological changes of
      periodontal tissue observed. Tumor necrosis factor (TNF) expression was examined
      in placenta by real-time quantitative polymerase chain reaction analysis.
      RESULTS: The animal model of chronic periodontitis was successfully established.
      Experimental group delivered 30 offspring and the control group 56 offspring. The
      average number of pups born alive per litter in experimental group (4.1 +/- 2.2)
      was significantly lower than that in control group (9.2 +/- 2.2), P < 0.05. The
      birth weight of pups in experimental group [(5.01 +/- 0.43) g] was significantly
      lower than that in the control group [(5.79 +/- 0.53) g], P < 0.05. The relative
      quantitative expression of TNF was (1.807 +/- 0.265) in experimental group the
      and (1.003 +/- 0.021) in the control group (P = 0.001). CONCLUSIONS: Chronic
      periodontitis may be related to preterm low birth weight.

PMID- 21733380
TI  - [Effects of Bushenguchiwan on expression of matrix metalloproteinase-13 in rats'
      periodontium].
AB  - OBJECTIVE: To investigate the influence of Bushenguchiwan on expression of matrix
      metalloproteinase-13 (MMP-13) in periodontium of rats with experimental
      periodontitis. METHODS: The model of experimental periodontitis of rats was
      established and treated by Bushenguchiwan with different doses. The periodontal
      tissues from groups of different doses were immunohistochemically stained by
      antibody of MMP-13. The expression of MMP-13 was examined and semi-quantitative
      analysis of signals performed by integrated absorbance. RESULTS: MMP-13 was
      intensely positive in gingival epithelial cells and periodontal fibroblasts in
      periodontitis models and negative in normal rat periodontal tissues. After 30
      days of Bushenguchiwan treatment with high dose, middle dose and low dose, the
      expression of MMP-13 (2.9103 +/- 0.5534, 3.6588 +/- 0.4330, 4.4550 +/- 0.4255)
      was down-regulated respectively compared with model rats (5.3233 +/- 0.7993), P <
      0.05. After 60 days of treatment the expression of MMP-13 (2.1855 +/- 0.5381,
      2.8558 +/- 0.4759, 3.8980 +/- 0.5885) was down-regulated more significantly. with
      model rats (6.2693 +/- 0.4538), P < 0.05. CONCLUSIONS: Bushenguchiwan could down
      regulate the expression of MMP-13 in rats' periodontium and the high dose group
      had better effect.

PMID- 21733381
TI  - [Orthodontic treatment of skeletal Class III patients with mandibular third molar
      extraction in both post-puberty and adult].
AB  - OBJECTIVE: To assess the skeletodental changes after extracting mandibular third
      molars in skeletal Class III patients in both post-puberty and adult. METHODS:
      Nineteen skeletal Class III patients in post-puberty or adult (16 female, 3 male)
      successfully treated with extracting mandibular third molars were included in the
      study. Cephalograms were analyzed to assess the skeletal and dental changes
      before and after treatment. Paired t-test was performed for statistical analysis
      of the data. RESULTS: The results revealed that the main changes were upright
      [(12.37 +/- 6.81) degrees ] and distal movement [(3.16 +/- 1.23) mm] of the
      mandibular molars, and retraction [(1.98 +/- 1.36) mm] of the mandibular
      incisors. There was a significant improvement in overjet [(2.75 +/- 1.65) mm].
      CONCLUSIONS: The lower molars and incisors could be distalized significantly with
      extraction of the lower third molars.

PMID- 21733382
TI  - [Preoperative Doppler evaluation of vascular perforators in the anterolateral
      thigh flap harvest].
AB  - OBJECTIVE: To evaluate the accuracy of Hadeco ES-1000spm hand-held doppler during
      the anterolateral thigh (ALT) flap harvest. METHODS: Twenty-five patients (26
      sides) with ALT flaps for head and neck reconstruction between May 2005 and May
      2010 received preoperative Doppler examination for the location of the cutaneous
      perforators of ALT flaps. The Doppler signals and body mass index (BMI) were
      recorded preoperatively according to ABC system. The locations of Doppler signals
      and of the actual cutaneous perforators at surgery were plotted and compared. The
      diameter of perforators was measured. RESULTS: One to three cutaneous perforators
      of the ALT flap were consistently found at specific locations. They were named
      perforators A, B, C from proximal to distal. Perforators A, B and C were present
      in 15 (58%), 24 (92%) and 20 (77%) cases and the diameter (> 0.5 mm) of A, B and
      C were 11/15, 22 (92%) and 8 (40%) respectively. The Doppler signal was within
      0.5 cm of the actual perforator location in 85% flaps. The accuracy of Doppler
      decreased with increase of BMI. CONCLUSIONS: Preoperative assessment by hand-held
      Doppler is useful in predicting the perforator vessels' locations and diameter
      although it's accuracy is limited.

PMID- 21733383
TI  - [Evaluation of promoting the oral cavity health measures of rural AIDS
      patients/HIV-carriers].
AB  - OBJECTIVE: To survey the status of oral cavity hygiene knowledge, attitude and
      practice (KAP) of rural acquired immunodeficiency syndrome (AIDS) patients and
      human immunodeficiency virus (HIV) carriers and take corresponding intervention
      measures to improve the oral health of these patients. METHODS: From May to
      August in 2009, the methods of anonymous face to face structured interview and
      oral examination at the scene were carried out at the baseline in rural AIDS
      patients/HIV-carriers. According to the results of the survey, intervention
      measures were taken. The results of the intervention and the oral hygiene status
      were compared before and after the intervention. RESULTS: The oral health status
      of 82 AIDS patients and HIV-carriers were in poor before the intervention, and
      the knowledge of AIDS-related oral health of 76 AIDS patients and HIV-carriers
      was promoted after interventions, "scaling can spread AIDS" were 22 cases (27%),
      and after the intervention 41 patients (54%) think that can spread (chi(2) =
      20.066, P < 0.001). The oral diseases of related AIDS were decreased
      dramatically, 68 patients (83%) had gingivitis before intervention and 47 cases
      (62%) after the intervention (chi(2) = 8.852, P = 0.003). The personal oral
      cavity hygiene and related oral KAP of AIDS caused by subjective factors had
      improved to different extent, "brushing teeth over 3 min at every turn", there
      were over 36 cases (44%) before intervention and 45 patients after intervention
      (59%) (chi(2) = 4.017, P = 0.045). CONCLUSIONS: The oral hygiene and KAP of AIDS
      patients and HIV-carriers in rural areas were poor and improved after
      intervention.

PMID- 21733384
TI  - [Adoption of the condyle position of patients with extensive tooth wear during
      occlusal rehabilitation].
AB  - OBJECTIVE: To evaluate the adoption of the condyle position of patients with
      extensive tooth wear during occlusal rehabilitation, and the correlation between
      increased vertical dimensions and the changes of joint spaces. METHODS: Twenty
      seven patients (five from Beifang hospital, others from Peking University School
      and Hospital of Stomatology) with extensive tooth wear were selected and received
      occlusal rehabilitation treatment. The radiographs of standard Schullers position
      were taken before treatment (stage 1), 1 month following delivery of temporary
      restoration (stage 2), and 1 month following delivery of permanent restoration
      (stage 3). RESULTS: The superior, anterior and posterior joint spaces were (3.24
      +/- 0.16), (2.06 +/- 0.11), (1.89 +/- 0.13) mm at stage 1; (3.61 +/- 0.15), (1.94
      +/- 0.10), (2.52 +/- 0.11) mm at stage 2; (3.49 +/- 0.19), (1.93 +/- 0.10), (2.40
      +/- 0.13) mm at stage 3. The posterior joint spaces at stage 2 and stage 3 were
      significantly larger than that at stage 1(P < 0.01). The superior spaces at stage
      2 were significantly larger than that at stage 1 (P < 0.05). No correlations
      between the increased vertical dimensions and the changes of joint spaces were
      found in the three stages (P > 0.05). CONCLUSIONS: The condyle positions in the
      patients with extensive tooth wear changed after occlusal rehabilitation.

PMID- 21733385
TI  - [Effects of cleaners on the color stability of prosthesis silicone rubbers].
AB  - OBJECTIVE: To evaluate the effect of different cleaners on the color stability of
      two silicone rubbers used for maxillofacial prosthesis, and to provide
      recommendations for clinical use. METHODS: Thirty skin-color columniform
      specimens (12 mm diameter, 10 mm height) of two silicone rubber (A:A-2000; Z:ZY
      1) were prepared, randomly divided into 6 groups according to the table of random
      number, and cleaned with the following solutions: isopropyl alcohol (I), three
      kinds of denture cleaners (P: Polident, S: Steradent, C: Cleansoft) and distilled
      water (D), simulating the total immersion time of 1 year (1, 15, 10, 3 and 10 min
      each time respectively). Control group was kept in dark place without treatment.
      The L(*), a(*), b(*) value were tested before and after immersion. Then color
      difference value was calculated. RESULTS: Color differences were different among
      groups. Color difference in group I (A: 2.15, Z: 2.00) were significantly greater
      than that in any other group. There were no significant differences between
      groups using denture cleaner P (A: 0.36, Z: 0.36), C (A: 0.42, Z: 0.37) and S (A:
      0.33, Z: 0.38), and group D (A: 0.22, Z: 0.23). CONCLUSIONS: Isopropyl alcohol
      causes the most severe fading, and denture cleaners and distilled water cause
      obscure fading.

PMID- 21733386
TI  - [Piezoelectric surgery in maxillary sinus floor elevation with hydraulic
      pressure].

PMID- 21733387
TI  - [Prosthodontic treatment of congenital tooth agenesis III. Prosthodontic
      principles of congenital tooth agenesis].

PMID- 21733388
TI  - [Progress in studies on Wnt signaling pathway in oral medicine].

PMID- 21733389
TI  - [Improving cytotoxicity of resin-base materials by N-Acetylcysteine].

PMID- 21733390
TI  - [The leading role of the concept of damage control surgery in severe liver
      trauma].

PMID- 21733391
TI  - [Study of bioartificial liver based on translational medicine].

PMID- 21733392
TI  - [The dilatation of the proximal neck after endovascular repair of abdominal
      aortic aneurysm].
AB  - OBJECTIVES: To review the dilatation of the proximal neck in abdominal aortic
      aneurysm (AAA) after endovascular repair (EVR), and to analyze the factors
      contributed to these changes. METHODS: From January 1997 to January 2007, a total
      of 45 patients treated by EVR met the inclusion criteria. There were 44 male and
      1 female patients, with an average age of (69 +/- 17) years. The patients were
      all asymptomatic abdominal aortic aneurysm, combined hypertension in 37 cases,
      coronary heart disease in 40 cases. All the patients had the complete
      preoperative enhanced CT information, and accepted more than 6 months of regular
      enhanced CT follow-up (1, 3, 6, 12 months after surgery and annually thereafter).
      The proximal aneurysm neck diameter increase was determined by CT, increase over
      2 mm as having change, less than 2 mm as no change. RESULTS: The average follow
      up interval was (34 +/- 25) months (ranging from 9 to 100 months). The mean
      preoperative proximal neck diameter was (21.5 +/- 2.3) mm, and (22.4 +/- 2.4) mm
      one month after operation and (24.0 +/- 2.8) mm at the latest follow-up. The
      increase of proximal neck diameter was detected in 71.1%. The oversizing
      percentage was 19% +/- 6%. The incidence of proximal neck over-sizing stent-graft
      in diameter was 6.7%. The incidence of no dilation at proximal neck diameter was
      97.4%, 68.6%, 39.3% and 3.3% at 16, 24, 36 and 96 months postoperatively
      respectively. The stent-graft migration was detected in 22.2% patients, and the
      migration distance was (7.0 +/- 1.3) mm (ranging from 0 to 9.5 mm). There were no
      case which the migration oversized 10 mm or need to reintervention. CONCLUSIONS:
      The more oversizing percentage, the more dilatation in the proximal neck. The
      stent-graft migration and the dilatation of the proximal neck might have effect
      on each other.

PMID- 21733393
TI  - [The anatomy features and surgical significance of the pulmonary circuits of
      pulmonary atresia with ventricular septal defect and major aortopulmonary
      collateral arteries].
AB  - OBJECTIVES: To analyze the anatomy features of the pulmonary circuits in the
      patients with pulmonary atresia (PA) with ventricular septal defect (VSD) and
      major aortopulmonary collateral arteries (MAPCA), and discuss the clinical
      significance. METHODS: From April 2002 to June 2010, the anatomy features of
      pulmonary circuits in 33 patients with PA/VSD/MAPCA were examined and analyzed.
      There were 21 male and 12 female patients. The age ranged from 11 months to 29
      years. The anatomic types of PA/VSD included group B for 22 cases, group C for 11
      cases. Thirty-one patients of them underwent 33 operative procedures. The
      operations included aorta-pulmonary shunt in 8 cases, one stage unifocalization
      with VSD open in 2 cases, complete repair in 23 cases. RESULTS: Twenty-nine
      (87.9%) patients had native pulmonary arteries, 6 of them were normal size and 23
      were hypoplastic size. Four patients (12.1%) had no native pulmonary arteries.
      The postoperative oxygen saturation of the patients undergone shunt and one stage
      unifocalization was increased to 83% to 90%. There was one early death after
      complete repair because of multiorgan function failure. There were 4 cases of
      severe low cardiac output and 3 cases of respiratory function failure. Sixteen
      patients after complete repair were followed up more than one year. The
      postoperative right ventricular pressure was 41 to 99 mmHg (1 mmHg = 0.133 kPa).
      The ejection fraction value was more than 50% in 14 patients and less than 50% in
      2 patients. Two patients had medium pulmonary insufficiency. CONCLUSIONS: An
      individualized approach based on the anatomy of the pulmonary circuits permits
      achievement in the patients with PA/VSD/MAPCA. The surgical strategy for
      PA/VSD/MAPCA mainly depends on the anatomy features of native pulmonary arteries,
      confluent pulmonary arteries and MAPCA.

PMID- 21733394
TI  - [The study of resting energy expenditure equation for short bowel syndrome
      patients].
AB  - OBJECTIVES: To determine the accuracy of resting energy expenditure (REE)
      calculated by using the Harris-Benedict (HB) equation, Food and Agriculture
      Organization/World Health Organization/United Nations University (FAO/WHO/UNU)
      equations (FAO equations), Shizgal-Rosa (SR) equation and the LIU equation in
      patients with short bowel syndrome (SBS). In addition, to explore the
      relationship between measured REE and body weight, fat free mass, body cell mass,
      fat mass and fat mass percent. METHODS: Fourty-one SBS patients including 30 male
      and 11 female, aged from 18 to 60 years admitted between January 2001 and October
      2010 were enrolled in this study. All patients required long-term parenteral or
      enteral plus parenteral nutrition support. Their mean age and mean stature were
      (37 +/- 16) years and (164.3 +/- 9.0) cm, and the average body weight and
      residual small intestine was (47.4 +/- 9.3) kg and (52 +/- 45) cm. Measured REEs
      and calculated REEs of SBS patients were estimated respectively by indirect
      calorimetry and REE equations, and then defined the difference of them. And body
      mass were metered by body composition analyzer. RESULTS: A significant
      correlation was found between measured REEs (1218 +/- 293) Kcal and calculated
      REEs from the HB equation (r = 0.588, P < 0.01), the SR equations (r = 0.591, P <
      0.01), the FAO equations (r = 0.411, P < 0.01) and the LIU equation (r = 0.585, P
      < 0.01). In the total sample, the paired t test between measured REEs and REEs
      derived from the HB equation, SR equation and FAO equation showed no significant
      difference (P > 0.05). However, measured REEs were significantly higher than REEs
      calculated using the LIU equations by 14.17% (P < 0.01). There was also a
      significant correlation between measured REEs and body weight, fat free mass and
      body cell mass (r = 0.548, 0.641 and 0.581). CONCLUSIONS: Indirect calorimetry is
      preferred when an accurate REE estimate of SBS patients is necessary. However, if
      this machine is not available, SR equation is recommended to use and LIU equation
      must be avoided. Fat free mass may be more useful than body weight in REE
      calculation.

PMID- 21733395
TI  - [Analysis of factors of formation and development about degenerative lumbar
      scoliosis].
AB  - OBJECTIVES: To investigate the correlation between scoliosis angle and the
      asymmetric index of degenerative lumbar scoliosis, the degree of intervertebral
      disc degeneration, decreased bone density. METHODS: As a retrospectively study, a
      total of 96 patients with degenerative lumbar scoliosis were retrospectively
      enrolled from January 2002 to August 2010 as scoliosis group, meanwhile 96
      patients with lumbar spinal stenosis matched in gender, age and body mass index
      (BMI) were selected as control group. All patients were studied with plain
      radiographs, MRI and dual energy X-ray absorptiometry at presentation.
      Radiographic measurements include Cobb angle, the height of the convex and
      concave side of the apical disc and the contiguous disc superiorly and
      inferiorly, the height of the convex and concave side of the apical and the
      contiguous vertebral body superiorly and inferiorly in scoliosis group, the
      height of L(2-3), L(3-4), L(4-5) discs and the height of L(2-4) vertebral body in
      control group. The average relative signal intensity of lumbar intervertebral
      disc and cerebrospinal fluid in T2WI sagittal image was measured in apex
      intervertebral disc and adjacent discs by Adobe Photoshop 6.0 in scoliosis group,
      which was measured in L(2-3), L(3-4), L(4-5) disc in control group. The bone
      density of lumbar, femoral neck, trochanter, and Ward's triangle regions were
      measured with dual-energy X-ray absorptiometry. RESULTS: The intervertebral disc
      height in convex side was greater than the height in the concave side [(40 +/- 7)
      mm vs. (28 +/- 7) mm, P < 0.01], the vertebral body height in convex side was
      greater than the height in the concave side [(76 +/- 12) mm vs. (72 +/- 10) mm, P
      = 0.016] in scoliosis group. There was significant statistically difference in
      the degenerative degree of intervertebral discs between two groups (P = 0.003).
      There was significant statistically difference of the average T-value and the
      rate of osteoporosis between two groups (P < 0.01). Multiple linear regression
      analysis showed that the asymmetric disc index, the degenerative degree of
      intervertebral disc and osteoporosis were the predominant correlative factors,
      which affected the development of degenerative lumbar scoliosis. CONCLUSIONS:
      Degenerative lumbar scoliosis is always accompanied by the height asymmetry of
      intervertebral discs and vertebral body from convex and concavity sides. There is
      positive correlation between the angle of scoliosis and the asymmetric disc
      index, the degeneration of intervertebral disc, and negative correlation between
      the angle of scoliosis and the bone density (T-value).

PMID- 21733396
TI  - [The efficacy and complications of posterior hemivertebra resection with
      monosegmental fusion for congenital scoliosis].
AB  - OBJECTIVE: To evaluate the efficacy and complications of posterior hemivertebra
      resection with monosegmental fusion in the treatment of congenital scoliosis.
      METHODS: Thirty consecutive cases of congenital scoliosis managed by posterior
      hemivertebra resection with monosegmental fusion of the two adjacent vertebra
      were investigated retrospectively. Radiographs were reviewed to determine the
      coronal curve magnitude and sagittal alignment preoperatively, postoperatively
      and at last follow-up. Operative reports and patient charts were reviewed to
      record any perioperative and late complications. RESULTS: The total number of
      resected hemivertebra was 30. Mean operation time was 193.8 min with average
      blood loss of 369.0 ml. The segmental scoliosis was corrected from 36.4 degrees 
      to 4.9 degrees  with a correction rate of 86.5%, and segmental kyphosis
      (difference to normal segmental alignment) from 21.2 degrees  to 6.6 degrees 
      with a correction rate of 68.9%. The trunk shift was improved from 17.1 to 8.8
      mm. The correction of the compensatory cranial and caudal curve were 74.9% and
      75.1%. There were 1 delayed wound healing, 2 pedicle cutting and 1 rod breakages.
      Radiolucent gaps were found on the lateral view in 2 cases without any sign of
      implant failure and correction loss. CONCLUSIONS: Posterior hemivertebra
      resection with monosegmental fusion of the two adjacent vertebra allows for early
      intervention in very young children. Excellent correction in the frontal and
      sagittal planes can be obtained. And a short segment of fusion allows for normal
      growth in the unaffected parts of the spine. The most common complication is
      implant failure.

PMID- 21733397
TI  - [A comparative study on the surgical outcomes of spinal fusion in adolescent
      idiopathic scoliosis patients with or without triradiate cartilages closed].
AB  - OBJECTIVE: To investigate the effect of potential spinal growth on the posterior
      only spinal instrumentation of adolescent idiopathic scoliosis (AIS). METHODS:
      From June 2003 to October 2007, 40 patients received posterior-only spinal
      instrumentation. Group of open triradiate cartilage (Group A) included 16 female
      AIS patients with mean age of 11.8, and group of closed triradiate cartilages
      (Group B) covered 24 female AIS patients with mean age of 13.7. The mean
      preoperative Cobb angles of Group A and B were 53.3 degrees  and 49.6 degrees 
      respectively, and the mean kyphosis in the sagittal plane was 27.7 degrees  and
      27.8 degrees  respectively. RESULTS: The post-operative Cobb angles were 22.2
      degrees  (Group A) vs. 20.7 degrees  (Group B) (P = 0.34) with correction rate of
      58.3% (Group A) vs. 57.7% (Group B) (P = 0.83). The mean Cobb angles at final
      follow-up were 24.8 degrees  (Group A) vs. 21.1 degrees  (Group B) (P = 0.05)
      with the correction loss of 5.3% (Group A) vs. 1.0% (Group B) (P = 0.01). In the
      sagittal plane, the average post-operative kyphosis was 22.5 degrees  (Group A)
      vs. 23.9 degrees  (Group B) (P = 0.49) with correction of 5.2 degrees  (Group A)
      vs. 3.9 degrees (Group B) (P = 0.63). The mean kyphosis at final follow-up was
      20.8 degrees (Group A) vs. 24.7 degrees (Group B) (P = 0.04) with the correction
      loss of -1.7 degrees  (Group A) vs. 0.8 degrees (Group B) (P = 0.01). Group A
      showed obvious correction loss in the coronal plane and decrease of kyphosis in
      the sagittal plane. Adding on phenomenon was found in 2 cases with Lenke type I
      with selected fusion in Group A, but not in Group B. CONCLUSIONS: Although
      similar post-operative correction is found in AIS patients with OTRC or CTRC, the
      loss of correction and "adding on phenomenon" are more likely to happen in
      patients with OTRC.

PMID- 21733398
TI  - [Impact factors for hidden blood loss after primary total knee arthroplasty].
AB  - OBJECTIVE: To investigate the relative factors for hidden blood loss (HBL) after
      primary total knee arthroplasty (TKA). METHODS: A retrospective study of 422
      consecutive patients who underwent primary TKA between October 2007 and August
      2009 was carried on. There were 60 male and 362 female patients with a mean age
      of 65.7 years. The HBL was calculated according to Gross formula. The effect of
      patient gender, age, body mass index (BMI), pre-operative diagnosis, unilateral
      or simultaneous bilateral TKA, tourniquet time, type of prosthesis, postoperative
      anticoagulation method and deep vein thrombosis (DVT) on the postoperative HBL
      were analyzed. RESULTS: The HBL in patients underwent unilateral TKA was
      significantly lower than that in those underwent simultaneous bilateral TKA
      [(1284 +/- 207) ml vs. (2248 +/- 504) ml, P = 0.000]. Unvaried analysis showed
      that the HBL were associated with BMI, tourniquet time, prosthesis type and
      postoperative anticoagulation method. Multivariate linear regression analysis
      showed that the impact factors of postoperative HBL include BMI, tourniquet time
      and prosthesis type. CONCLUSIONS: BMI, bilateral simultaneous TKA, tourniquet
      time and intercondylar open prosthesis impact the HBL after primary TKA. However,
      the influence of gender, age, diagnosis, postoperative anticoagulation method and
      DVT on the HBL are not significant.

PMID- 21733399
TI  - [Operative experiences on transumbilical single incision laparoscopic
      cholecystectomy].
AB  - OBJECTIVE: To study the feasibility and safety of transumbilical single incision
      laparoscopic cholecystectomy. METHODS: Eighty-two cases with gallbladder diseases
      were underwent with transumbilical single incision laparoscopic cholecystectomy.
      Some difficulties and countermeasure in operations were analyzed. RESULTS: Nine
      in all patients were converted because of the surrounding inflammation of
      gallbladder, difficult to dissect in Calot's triangulation and variation of
      gallbladder artery. Of them, 6 cases converted to two-hole laparoscopic
      cholecystectomy and 3 cases to open operation. Other 73 cases were successfully
      operated with transumbilical single incision laparoscopic cholecystectomy. The
      success rate was 89.0%. The average operative duration was 48.4 min. The average
      operative blood loss was 20.8 ml. Patients returned to liquid food on the first
      day after operation. Hospital duration was 3 ~ 6 d. During 13.7 months of follow
      up, there was no bile duct injury, large bleeding, incision infection, bile
      fistula and umbilical hernia. The incision healed well. The scar in umbilicus was
      concealing and difficult to be observed. CONCLUSIONS: Transumbilical single
      incision laparoscopic cholecystectomy is safe and feasible. The difficulties in
      technique are easy to be broken through.

PMID- 21733400
TI  - [The effect of intra-abdominal hypertension on hemodynamics of acute necrotizing
      pancreatitis in porcine model].
AB  - OBJECTIVE: To assess the effect of intra-abdominal hypertension (IAH) on
      hemodynamics of severe acute pancreatitis (SAP) in porcine model. METHODS:
      Following baseline registrations, SAP was induced in 12 animals. The N(2)
      pneumoperitoneum was used to increase the intra-abdominal pressure to 30 mmHg (1
      mmHg = 0.133 kPa) in 6 of 12 SAP animals thereafter and keep constant during the
      experiment. The investigation period was 12 h. Heart rate, cardiac output (CO),
      central venous pressure (CVP), mean arterial pressure and pulmonary arterial
      wedge pressure (PAWP) were continuously measured with the aid of balloon tipped
      flow-directed catheter and electrocardiography monitor. Oxygen partial pressure
      of artery (PaO(2)), carbon dioxide partial pressure of artery (PaCO(2)), ScvO(2),
      base excess (BE), and blood lactic acid (LAC) were measured by acid-base
      analysis. RESULTS: In the IAH group, CO decreased significantly at 12 h, CVP and
      PAWP increased significantly at 3 h, 6 h and 12 h compared with SAP group (all P
      < 0.05). Peak inspiration pressure increased immediately after pneumoperitoneum
      in the IAH group, to (50.2 +/- 3.1) cmH(2)O (1 cmH(2)O = 0.098 kPa) and (49.8 +/-
      0.9) cmH(2)O at 6 h and 12 h respectively. The pH, PaO(2), ScvO(2) and BE showed
      a tendency to fall in the IAH group. PaCO(2) and LAC were increased significantly
      in the IAH group (all P < 0.05). CONCLUSIONS: There were remarkable and
      relatively irreversible effects on global hemodynamics in response to sustained
      IAH of 12 h with the underlying condition of SAP. Abdominal decompression is
      beneficial for patients of SAP with IAH.

PMID- 21733401
TI  - [The hyposensitization of oval cell to antiproliferative effect of transforming
      growth factor beta1 by hepatitis B virus X gene].
AB  - OBJECTIVE: To determine whether hepatitis B virus X (HBX) protein expression
      affect the oval cells' response to anti-proliferative effect of transforming
      growth factor beta1 (TGFbeta1) in oval cells. METHODS: Real-time PCR, Western
      blot analysis were performed to detect the expression of TGFbetaRII in HBX
      transfected oval cells named HBX-EGFP-LE/6, and EGFP-LE/6, LE/6 control cells. In
      addition, exogenous TGFbeta1 was added into all three oval cell lines, MTT assay
      was preformed to clarify different responses to the anti-proliferative effect of
      TGFbeta1. RESULTS: The TGFbetaRII mRNA levels in LE/6 and EGFP-LE/6 cells were
      (10.2 +/- 1.8) and (8.8 +/- 0.9) folds of those in HBX-EGFP-LE/6 cells, the
      difference was significant (P < 0.05). HBX protein expression also reduced the
      protein levels of TGFbetaRII in HBX-EGFP-LE/6 oval cells, compared to the control
      cells. The MTT results exhibited that, after TGFbeta1 addition, proliferative
      inhibition rate in the HBX-EGFP-LE/6 cells was 18.1% +/- 1.5% while those in
      control cells were 42.2% +/- 2.8% and 41.9% +/- 5.0%, the difference was
      significant (P < 0.01). CONCLUSION: HBX protein expression affects TGFbetaRII
      transcriptional activity and protein synthesis, and insensitive oval cells to
      anti-proliferative effect of TGFbeta1.

PMID- 21733402
TI  - [Biomechanical stability of unilateral pedicle screw fixation on cadaveric model
      simulated two-level posterior lumbar interbody fusion].
AB  - OBJECTIVE: To analyze the biomechanical efficacy of unilateral pedicle screw
      fixation on human cadaveric lumbar spine model simulated by two-level posterior
      lumbar interbody fusion (PLIF). METHODS: Six fresh-frozen adult human cadaveric
      lumbar spine motion segments (L(2)-S(2)) were simulated to unilateral/bilateral
      L(4)-S(1) PLIF constructs augmented by unilateral/bilateral pedicle screw
      fixation sequentially and respectively. All configurations were tested by MTS 858
      in the following sequential construct order: the intact, UI (unilateral
      instability), UIUF1C (unilateral instability via unilateral pedicle screw
      fixation plus one cage), BIUF1C (bilateral instability via unilateral pedicle
      screw fixation plus one cage), BIBF1C (bilateral instability via bilateral
      pedicle screw fixation plus one cage) and BI (bilateral instability without
      pedicle screw and cage). Each specimen was nondestructively tested in
      flexion/extension, lateral bending, and axial rotation. An axial compressive load
      ranged from 40 N to 360 N and the maximum peak moment of 8 N.m was applied during
      testing. The range of motion (ROM) and neutral zone (NZ) of fusion segment were
      recorded by a 6-Eagle Motion Analysis F40 system, and then statistic comparison
      were performed between different simulated constructs with One Way of ANOVA and
      Post hoc LSD tests. RESULTS: BIBF1C had the lowest ROM and NZ of L(4)-S(1) fusion
      segments in all loading models, which were significantly lower than those of any
      uninstrumented construct (the intact, UI and BI) (P < 0.05). In
      flexion/extension, lateral bending, and axial rotation, the ROM of UIUF1C was
      respectively 2.53 +/- 1.12, 4.03 +/- 2.19, 2.78 +/- 1.00 and the NZ of UIUF1C was
      respectively 1.14 +/- 0.70, 1.96 +/- 1.13, 1.28 +/- 0.71, which were
      significantly lower than those of the intact (P < 0.05). Compared to BIBF1C, the
      ROM and NZ were respectively increased 60.13% and 17.52% in flexion/extension,
      315.46% and 243.86% in lateral bending, 8.17% and 6.20% in axial rotation,
      however, there were no significant differences between these two constructs (P >
      0.05). In lateral-bending and axial rotation, the ROM and NZ of BIUF1C were
      significantly higher than those of BIBF1C (P < 0.05). In flexion/extension, the
      ROM and NZ of BIUF1C were higher than those of BIBF1C but there were no
      significant differences (P > 0.05). Compared to the intact, BIUF1C had lower ROM
      and NZ except for higher NZ in axial rotation, and there were significant
      differences only in flexion/extension (P < 0.05). CONCLUSIONS: All tested two
      level unilateral fixation on simulated human cadaveric model with unilateral PLIF
      can achieve similar initial biomechanical stability in comparison with two-level
      bilateral pedicle screw fixation. However in most test modes, two-level
      unilateral pedicle screw fixation on simulated human cadaveric model with
      bilateral PLIF can not achieve enough biomechanical efficacy in comparison with
      two-level bilateral pedicle screw fixation.

PMID- 21733403
TI  - [Research on the effects of PIAS3 expression on the invasion of glioma TJ905
      cells].
AB  - OBJECTIVES: To investigate the function and possible mechanisms of PIAS3
      expression on the invasion of TJ905 cells. METHODS: PIAS3 overexpression vectors
      were constructed and PIAS3 siRNA were chemically synthesized, which were
      separately transfected into TJ905 cells for upregulation or downregulation of
      PIAS3 expression levels in TJ905 cells. After that, the invasive effects of TJ905
      cells were measured by Transwell assay, and the expression of PIAS3, tissue
      inhibitor of metalloproteinases (TIMP)3, matrix metalloprotease (MMP)-2, and MMP
      9 were identified by Western blot. RESULTS: In vitro transfection efficiency of
      plasmids and oligonucleotides were separately 85.3% +/- 3.1% and 95.1% +/- 2.9%.
      PIAS3 overexpression plasmid transfection in vitro could effectively improve the
      expression of PIAS3 protein in TJ905 cells and inhibit the invasion of TJ905
      cells (P < 0.05), and cell penetration ratio reduced from 87.9% +/- 9.3% to 37.3%
      +/- 7.9% compared with control group, while it upregulated TIMP3 and
      downregulated MMP-2, MMP-9 protein expression (P < 0.05); PIAS3 siRNA
      transfection could inhibit the PIAS3 protein expression of TJ905 cells and
      promote the invasion of TJ905 cells (P < 0.05), and cell penetration ratio
      increased from 83.9% +/- 7.1% to 93.2% +/- 3.1% compared with control group,
      while it downregulated TIMP3 and upregulated MMP-2, MMP-9 protein expression (P <
      0.05). CONCLUSION: PIAS3 expression is closely related to the invasion properties
      of glioma TJ905 cells.

PMID- 21733404
TI  - [Proteomic analysis between keloid and normal skin].
AB  - OBJECTIVE: To investigate and search correlative proteins of keloid by comparing
      the results of differential proteomic analysis between keloid and normal skin.
      METHODS: From January 2010 to June 2010 two-dimensional gel electrophoresis was
      used to define patterns of protein expression in keloid skin from 8 patients and
      matched normal skin from 3 patients. Differential expression protein spots were
      showed and analyzed by matrix-assisted laser desorption ionization-time of
      flying/time of flying (MALDI-TOF/TOF) mass spectrometry. RESULTS: This study
      succeeded to provide a two-dimensional protein profiling comparison between
      normal skin and keloid. Gel-analysis software identified an average of 2978 spots
      in keloid while 3053 spots in normal skin and statistical filtering yielded 40
      spots of a 4-fold change, 32 of which were identified by using mass spectrometry,
      20 were up-regulated and 12 were down-regulated. Functional analysis revealed
      that these proteins could be fractionated to carrier proteins (3 proteins),
      signal transduction proteins (4 proteins), proliferation and apoptosis related
      proteins (2 proteins), cytoskeleton proteins (6 proteins), extracellular matrix
      proteins (8 proteins), immunity related proteins (3 proteins), tumor related
      proteins (2 proteins), and function unknown protein (4 proteins). CONCLUSIONS:
      Proteomic analysis can identify the proteins with variance of keloid versus
      normal skin. The further research to these differential proteins may help reveal
      the pathogenesis of keloid and provide new treatments for keloid.

PMID- 21733405
TI  - In Situ intestinal perfusion of irinotecan: application to P-gp mediated drug
      interaction and introduction of an improved HPLC assay.
AB  - PURPOSE: To determine experimentally the intestinal permeability of the
      anticancer prodrug irinotecan, and to quantify the amount of its cytotoxic
      metabolite SN-38 that is intestinally excreted (exsorped) as a predictor of
      intestinal toxicity, and to assess the effect of p-glycoprotein (p-gp) inhibitors
      (verapamil as a model) on the permeability and toxicity of irinotecan. METHODS:
      Single pass intestinal perfusion of rat's whole length small intestines is
      applied to assess the permeability of the parent drug and quantify the
      intestinally excreted metabolite. The perfusion solution contained 30MUg/ml of
      irinotecan (control group) without or with verapamil (verapamil group). A simple
      reversed phase HPLC method with UV detection is developed and validated for
      simultaneous determination of irinotecan and SN-38 using camptothecin as an
      internal standard. RESULTS: HPLC-UV method found to be simple, specific,
      accurate, and precise. Effective permeability coefficient of irinotecan found to
      be 4.9+/-1.7 10-3 mm/min and was doubled in verapamil group (P=0.007). Average
      cumulative amount of SN-38 exsorped found to be 29 ng/cm over 2 hours perfusion
      time which was decreased to 15 ng/cm in verapamil group (P=0.016). CONCLUSIONS:
      in situ intestinal perfusion method was successfully applied to quantify the
      permeability of irinotecan and the exsorption of SN-38 in the same experiment, in
      a manner that robustly reflects real in vivo situation. P-gp inhibition using
      verapamil found to significantly enhance the intestinal permeability of
      irinotecan and potentially decrease the intestinal toxicity due to SN-38
      exposure.

PMID- 21733406
TI  - An overview of tuberculosis chemotherapy - a literature review.
AB  - Tuberculosis (TB) is a major threat in global public health. The emergence of HIV
      and also multi drug resistant (MDR) and extremely drug resistant (XDR)-TB poses a
      vital challenge to the control of the disease. For the last 40 years, no new anti
      TB drug has been discovered. This literature review provides a brief discussion
      of existing drugs and emerging drug targets, and also of the advantages of
      incorporating modern drug delivery systems and immune modulators in order to
      improve the existing treatment regimen in terms of better efficacy, reduced drug
      administration frequency, shortened period of treatment and reduced drug related
      toxicity. The investigation for new a drug target is essential in carrying on the
      fight against MDR and XDR-TB. However, owing to the enormous cost and time
      involved in new drug development, improvement of the existing treatment regimen
      is seen to be a valid alternative.

PMID- 21733407
TI  - In vitro photo-controlled drug release system based on amphiphilic linear
      dendritic diblock copolymers; self-assembly behavior and application as
      nanocarrier.
AB  - PURPOSE: A simple type of photoresponsive amphiphilic linear-dendritic diblock
      copolymer has been synthesized and investigated for its ability to act as a drug
      carrier. These structures contain hydrophilic polyethylene oxide monomethyl ether
      (PEOM) as hydrophilic block and carbosiloxane dendritic branches as hydrophobic
      block grafted by two and six Magneson II as azo chromophore, PEOM-Azo, 2 and PEOM
      Azo, 6 respectively. Self-assembling of the amphiphilic macromolecules of PEOM
      Azo, 2 and PEOM-Azo, 6, briefly were represented as PEOM-Azo [2, 6], leads to the
      formation of their micellar aggregates in aqueous media. METHOD: Their micellar
      properties such as critical micelle concentration (CMC), aggregation number and
      thereby total numbers of azo-groups in each micellar aggregates were determined.
      Also, they were characterized by TEM, SEM and DLS. RESULTS: The unloaded
      aggregates examined under UV light (366 nm), which were observed to be smaller
      than 300 nm. The release patterns of the encapsulated drug molecule from these
      aggregates were investigated as regulated by the PEOM-Azo [2, 6] systems in trans
      and cis forms. CONCLUSION: A comparison of the release behavior of the loaded
      PEOM-Azo [2, 6] systems indicated that the release rate of the encapsulated
      active molecules from the carriers was slower when the azo moieties were in trans
      form as compared to that the azo in the cis form. The in vitro release behavior
      of drug from these polymeric systems represents potential of the carriers for
      controlled drug delivery.

PMID- 21733408
TI  - Preparation of chitosan-plasmid DNA nanoparticles encoding interleukin-12 and
      their expression in CT-26 colon carcinoma cells.
AB  - PURPOSE: Interleukin-12 (Il-12) as a cytokine has been proved to possess
      antitumor effects via stimulating the immune system. Non-viral gene delivery
      systems exhibit low toxicity and are easier to prepare compared to their viral
      counterparts. In this study, we aimed to prepare plasmid DNA loaded chitosan
      nanoparticles for expression of Il-12 and to evaluate their physicochemical
      characteristics, cytotoxicity and transfection efficiency in Murine CT-26 colon
      carcinoma cells. METHODS: Nanoparticles were prepared using a complex
      coacervation process at different N/P ratios and characterized in terms of size,
      zeta potential, polydispersity index, morphology, encapsulation efficiency and
      polyplex formation. The cytotoxicities and transfection efficiencies of the
      prepared polyplexes were evaluated by MTT assay and ELISA (for hIL-12, p70),
      respectively. RESULTS: Size and zeta potential varied from 76.73 to 867.03 nm and
      between 5.68 and 16.77 mV, respectively. Strong attachment of the DNA to chitosan
      was observed after polyplex preparation. Encapsulation efficiencies were high
      (72.97-94.87%). The transfection efficiencies of the prepared complexes were
      obviously higher than those of naked pDNA when N/P ratios were between 16 and 60.
      Maximum level of phIL-12 expression was obtained at (N/P = 16) with mean particle
      size of 381.83+/-82.77 nm (polydispersity index=0.44) indicating the improved
      transfection of pUMVC3-hIL12 about 2.80 times compared to that of the naked
      pUMVC3-hIL12. Prepared polyplexes were nontoxic to CT-26 cells. CONCLUSIONS:
      Chitosan-DNA nanoparticles at N/P = 16 with minimal cytotoxicity, can be used as
      suitable candidate for Il-12 delivery. This article is open to POST-PUBLICATION
      REVIEW. Registered readers (see "For Readers") may comment by clicking on
      ABSTRACT on the issue's contents page.

PMID- 21733409
TI  - Investigation of nanosized crystalline form to improve the oral bioavailability
      of poorly water soluble cilostazol.
AB  - PURPOSE: The aim of this study was to develop cilostazol (CLT) nanocrystals
      intended to improve its dissolution rate and enhance its bioavailability.
      METHODS: In this study, CLT nanosuspension was prepared by the anti-solvent and
      high-pressure homogenization method. The effects of the production parameters,
      such as the stabilizer concentration, pressure and number of cycles, were
      investigated. Characterization of the product was performed by scanning electron
      microscopy (SEM), Nitrogen adsorption, differential scanning calorimetry (DSC), X
      ray powder diffraction analysis (XRPD), X-ray Photoelectron Spectroscopy (XPS),
      particle size analysis and dissolution testing. Additionally, the comparison
      studies of oral bioavailability in beagle dogs of three type tables were
      performed. RESULTS: The images of SEM showed a spherical smooth CLT powder, and
      Nitrogen adsorption test revealed spray dried powder were porous with high BET
      surface area compared with that of raw CLT. DSC and XRPD results demonstrated
      that the combination of preferred polymorph B and C of CLT were prepared
      successfully, the saturation solubility of the nanosized crystalline powder is
      about 5 fold greater than that of raw CLT, and the dissolution rate was enhanced
      4 fold than that of raw CLT. The Cmax and AUC0-48h of CLT nanosized crystalline
      tablets were 2.1 fold and 1.9 fold, and 3.0 fold and 2.3 fold compared with those
      of the nanosized tablets and commercial tablets, respectively. CONCLUSION: The
      anti-solvent-high-pressure homogenization technique was employed successfully to
      produce cilostazol nanosuspensions. The bioavailability of CLT tablets prepared
      using spray dried nanosized crystalline powder after oral administration to dogs
      was markedly increased compared with that produced by nanosized tablets and
      commercial tablets, because of its greater dissolution rate owing to its
      transition of the crystalline state to form C and form B, reduced particle size
      and porous structure with increased surface area.

PMID- 21733410
TI  - How critical is the duration of the sampling scheme for the determination of half
      life, characterization of exposure and assessment of bioequivalence?
AB  - In noncompartmental analysis, poor characterization of the terminal elimination
      rate constant (Kel) will lead to biased results for half-life and total exposure
      (AUCinf), providing incorrect relative bioavailability and bioequivalence
      conclusions. We set out to determine if the sampling scheme duration was crucial
      for proper half-life and AUCinf determination. Profiles for 1000 subjects were
      simulated with a sampling scheme covering five half-lives. Concentrations were
      gradually removed from the end of the profile to determine if precision and bias
      in the half-life and AUCinf values were affected. Additionally, 30 bioequivalence
      studies were simulated to determine the influence of unreliable AUCinf PK
      parameter on BE conclusions. Precision and bias became unacceptable for AUCinf
      and half-life if Kel was not determined with a sampling scheme covering at least
      2 and 4 half-lives, respectively. Bioequivalence conclusions also deteriorated if
      unreliable PK parameters were maintained. Sampling scheme duration is important
      when calculating noncompartmental parameters. In conclusion, sampling scheme
      duration should be at least 4 times the average measured half-life in order to
      have confidence in the reported half-life values. Additionally, individual
      subject's pharmacokinetic parameters should be removed from the pivotal
      statistical analysis when their associated calculated half-life is longer than
      half of the total sampling interval.

PMID- 21733411
TI  - Clinical trial risk in Non-Hodgkin's lymphoma: endpoint and target selection.
AB  - PURPOSE: To quantify the clinical trial risk of new drug development in Non
      Hodgkin's lymphoma (NHL). Risk estimates for this disease have not been reported
      before. METHODS: We undertook a retrospective review of clinical trials in (NHL)
      in four subtypes to compare the success rate with the industry average. Our
      inclusion criteria required that a drug must initiate its phase I trial in one of
      the four NHL subtypes between 1998 and June 2008 in the US. In addition, clinical
      trials of new drug candidates that pertain to four subtypes of NHL were retrieved
      from clinicaltrial.gov. Drug candidates that did not meet these criteria were
      excluded from the study. RESULTS: The overall success rate (8-11%) was
      significantly lower than the industry standard (17%). Overall survival (OS) as a
      secondary outcome appeared more predictive than primary endpoints that were
      surrogate, of overall success. Further, targeted therapies appear more successful
      in these lymphoma sub-types than broad acting drugs. CONCLUSION: Clinical trial
      risk in NHL, with an 89% failure rate reported here, may be reduced by basing
      decisions on OS secondary endpoints and biologic drugs.

PMID- 21733412
TI  - Exposure of LS-180 cells to drugs of diverse physicochemical and therapeutic
      properties up-regulates P-glycoprotein expression and activity.
AB  - PURPOSE: Drug transporters are increasingly recognized as important determinants
      of variability in drug disposition and therapeutic response, both in pre-clinical
      and clinical stages of drug development process. The role P-glycoprotein (P-gp)
      plays in drug interactions via its inhibition is well established. However, much
      less knowledge is available about drugs effect on P-gp up-regulation. The
      objective of this work was to in vitro investigate and rank commonly used drugs
      according to their potencies to up-regulate P-gp activity utilizing the same
      experimental conditions. METHODS: The in vitro potencies of several drugs of
      diverse physicochemical and therapeutic properties including rifampicin,
      dexamethasone, caffeine, verapamil, pentylenetetrazole, hyperforin, and beta
      estradiol over broad concentration range to up-regulate P-gp expression and
      activity were examined. For dose-response studies, LS-180 cells were treated with
      different concentrations of the selected drugs followed by P-gp protein and gene
      expressions analyses. P-gp functionality was determined by uptake studies with
      rhodamine 123 as a P-gp substrate, followed by Emax/EC50 evaluation. RESULTS: The
      results demonstrated a dose-dependent increase in P-gp expression and activity
      following treatments. At 50 uM concentration (hyperforin, 0.1 uM), examined drugs
      increased P-gp protein and gene expressions by up to 5.5 and 6.2-fold,
      respectively, while enhanced P-gp activity by 1.8-4-fold. The rank order of these
      drugs potencies to up-regulate P-gp activity was as following: hyperforin >>>
      dexamethasone ~ beta-estradiol > caffeine > rifampicin ~ pentylenetetrazole >
      verapamil. CONCLUSIONS: These drugs have the potential to be involved in drug
      interactions when administered with other drugs that are P-gp substrates. Further
      studies are needed to in vivo evaluate these drugs and verify the consequences of
      such induction on P-gp activity for in vitro-in vivo correlation purposes.

PMID- 21733413
TI  - Effect of a 36-month pharmaceutical care program on the coronary heart disease
      risk in elderly diabetic and hypertensive patients.
AB  - PURPOSE: To examine the effect of a pharmaceutical care program on the coronary
      heart disease risk in elderly diabetic and hypertensive patients. METHODS: A
      total of 200 elderly (> 60 years) diabetic and/or hypertensive patients were
      recruited into a randomized, controlled, prospective clinical trial with a 36
      month follow-up, developed in a public primary health care unit in a municipality
      in the Brazilian State of Sao Paulo. A range of clinical measurements were
      evaluated at the baseline and up to 36 months afterwards. The intervention group
      patients received pharmaceutical care from a clinical pharmacist, whereas the
      control group patients received their usual care from the medical and nursing
      staff. The Framingham scoring method was used to estimate changes in the 10-year
      coronary heart disease risk scores of all the patients. RESULTS: A total of 194
      patients completed the study. Significant reductions (p < 0.05) in the mean
      values (baseline vs. 36 months) for the systolic blood pressure [156.7 mmHg vs
      133.7 mmHg; P < 0.001), diastolic blood pressure (106.6 mmHg vs. 91.6 mmHg; P <
      0.001),fasting glucose (135.1 mg/dL vs. 107.9 mg/dL; P < 0.001), hemoglobin A1C
      (7.7% vs. 7.0%; P <0.001), triglycerides (206.0 mg/dL vs. 152.5 mg/dL; P <
      0.001), low-density lipoprotein (LDL)cholesterol (112.4 mg/dL vs. 102.0 mg/dL; P
      < 0.001), high-density lipoprotein cholesterol (55.5 mg/dL vs. 65.5 mg/dL; P <
      0.001), total cholesterol (202.5 mg/dL vs. 185.9 mg/dL; P < 0.001), body mass
      index (26.2 kg/m2 vs. 26.1 kg/m2; P < 0.001), and abdominal circumference (103.2
      cm vs. 102.5 cm; P= 0.001) were observed in the intervention group, whereas no
      significant changes were verified in the control group. The mean Framingham risk
      prediction score in the intervention group was 6.8% at baseline and decreased to
      4.5%; P < 0.001) after 36 months, but remained unchanged in the control group.
      CONCLUSION: The pharmaceutical care program resulted in better clinical
      measurements and reduced the cardiovascular risk scores in elderly diabetic and
      hypertensive patients over a 36-month period.

PMID- 21733414
TI  - The glucosamine controversy; a pharmacokinetic issue.
AB  - Glucosamine (GlcN) is a naturally occurring aminosugar that is widely used to
      treat osteoarthritis despite controversial clinical trial results. Animal
      studies, on the other hand, unequivocally suggest anti-inflammatory and disease
      modifying effects for GlcN. Many explanations have been offered as to the root of
      the controversy. They include superiority of a crystalline sulphate salt over
      HCl, industry bias, insensitive assessment metrics and poor methodology. Herein,
      we rule out a difference in bioequivalence between GlcN salts and that of
      chemically equivalent doses and suggest additional factors; i.e., inconsistency
      in the chemical potency of some products used, under-dosing of patients as well
      as variable and erratic bioavailability indices for the lack of GlcN efficacy
      observed in some studies. Clinical trials using higher doses of pharmaceutical
      grade GlcN or formulations with greater bioavailability should yield positive
      results.

PMID- 21733415
TI  - Safety of liver surface instillation of plasmid DNA in normal and carbon
      tetrachloride-induced hepatitis mice.
AB  - PURPOSE: We previously demonstrated liver- and lobe-selective gene transfer
      following instillation of plasmid DNA (pDNA) onto the liver surface in mice.
      Safety concerns must be resolved prior to future clinical use. Thus, we
      investigated safety of liver surface instillation of pDNA in normal and hepatitis
      mice. METHODS: pDNA was instilled onto the liver surface in normal and carbon
      tetrachloride-induced hepatitis mice. Gene expression (luciferase activity) and
      serum transaminase activities were measured at appropriate time points. RESULTS:
      Transfection efficiency and target site selectivity were almost the same between
      the instillation of pDNA using a micropipette and a catheter. Serum transaminase
      activities 6 h after instillation of pDNA or a vehicle treatment using a
      micropipette were significantly higher than the no treatment mice, whereas
      instillation using a catheter did not raise serum transaminase activities
      throughout the tested time points, suggesting the safety of instillation using a
      catheter. This safety was also confirmed in hepatitis mice. A dose escalation
      study verified that liver surface instillation using a catheter did not raise
      serum transaminase at high doses with saturation of gene expression not only in
      normal mice, but also in hepatitis mice, supporting the safety of this method.
      CONCLUSIONS: We demonstrated that liver surface instillation of pDNA using a
      catheter did not raise serum transaminase activities. Information in this study
      will be useful for future clinical use of liver surface instillation of pDNA
      using a catheter.

PMID- 21733416
TI  - Safety assessment of potentially inappropriate medications use in older people
      and the factors associated with hospital admission.
AB  - PURPOSE: Potentially Inappropriate Medications (PIM) use in elderly people may be
      responsible for the development of Adverse Drug Reaction (ADR) which, when
      severe, leads to hospital admissions. OBJECTIVES: to estimate the prevalence of
      elderly who had used PIM before being admitted to hospital admission and to
      identify the risk factors and the hospitalizations related to ADR arising from
      PIM. METHODS: A descriptive and cross-sectional study was performed in the
      internal medicine ward of a teaching hospital (Brazil), in 2008. With the aid of
      a validated form, patients aged >= 60 years, with length of hospital stay >= 24
      hours, were interviewed about drugs taken prior to the hospital admission and the
      complaints/reasons for hospitalization. RESULTS: 19.1% (59/308) of older patients
      had taken PIM before hospital admission and in 4.9%; there were a causal relation
      between the PIM taken and the complaint reported. PIM responsible for admissions
      were: amiodarone, amitriptyline, cimetidine, clonidine, diazepam, digoxin,
      estrogen, fluoxetine, lorazepam, short-acting nifedipine and propranolol. 47.0%
      of the clinical manifestations of PIM-related ADR were: dizziness, fatigue,
      digoxin toxicity and erythema. Only polypharmacy was detected as a risk factor
      for the occurrence of ADR of PIM (p = 0.02). CONCLUSION: PIM use in elderly
      people is not a risk factor for ADR-related hospital admission. Probably, severe
      ADR, which lead to hospitalizations of older people, can be explained by
      idiosyncratic response or the predisposition of these patients to develop adverse
      drug events, whether or not drugs are classed as PIM.

PMID- 21733417
TI  - Efficacy of paracetamol versus diclofenac for Grade II ankle sprains.
AB  - BACKGROUND: Ankle sprains are usually treated with the RICE protocol often with
      nonsteroidal anti-inflammatory drugs (NSAID) for pain reduction. We evaluated the
      effect of diclofenac, an NSAID, versus paracematol in the reduction of pain and
      acute edema of severe ankle sprains. MATERIALS AND METHODS: Ninety patients, 18
      to 60 years old, with Grade II acute ankle sprains were randomized into two
      groups. Group A (45 patients) received for the first 10 days diclofenac 75 mg
      orally twice per day. Group B (45 patients) received paracetamol 500 mg orally
      three times per day for the same period. We evaluated ankle joint edema with the
      Figure-of-Eight method and with the volumetric method, as well as pain with the
      Visual Analogue Scale (VAS) in both groups. RESULTS: The patients had no
      significant differences concerning their baseline values (p > 0.05). The ankle
      joint edema was decreased in both groups (p < 0.001) but there was more edema in
      group A than in group B at the third post-traumatic day with both measurement
      methods (p = 0.028/0.025). By the tenth post-traumatic day no difference was
      found. Pain decreased in both groups at the third day and at the tenth day (p <
      0.001). CONCLUSION: According to these results, diclofenac and paracetamol had
      the same effect on pain reduction of ankle sprains but more acute ankle edema was
      present in patients who were treated with diclofenac than in patients who were
      treated with paracetamol.

PMID- 21733418
TI  - Alcohol sclerosing therapy is not an effective treatment for interdigital
      neuroma.
AB  - BACKGROUND: Alcohol sclerosing therapy has been reported as a safe and effective
      means of treating interdigital neuromas, both with or without ultrasound. The use
      of ultrasound introduces beside the ultrasound device, increased cost, and the
      need for skilled technicians and may reduce usability, especially in the
      outpatient clinic. We report a series of patients with interdigital neuroma
      treated using ethanol sclerosing therapy in a clinic setting without the use of
      ultrasound. MATERIALS AND METHODS: We retrospectively reviewed charts of 32
      consecutive patients who were enrolled to receive a series of sclerosing ethanol
      injections from June 2009 to April 2010 for the treatment of a painful
      interdigital neuroma. Plain radiographs and MRI scans were obtained if clinically
      indicated to assistance with the diagnosis. Duration and quality of symptoms were
      recorded and current pain levels were evaluated on a visual analog pain scale.
      Previous treatments, including orthotic use, corticosteroid injection, or prior
      neuroma resection were reported. A solution of 1 ml consisting of 20% ethanol and
      0.25% bupivacain solution was injected without the use of ultrasound into the
      affected webspace. The mixture was provided by the local pharmacy. Technical
      success was confirmed by the temporary resolution of pain following local
      anesthetic infiltration. If still symptomatic, an injection was repeated every 2
      weeks, with most patients receiving a series of four injections. Pain was
      evaluated on a visual analog pain scale at each visit. Treatment success was
      defined as resolution of pain as expressed by the patient. RESULTS: Of the 32
      patients successful relief of symptoms was only achieved in seven patients, while
      25 showed no significant reduction of symptoms and considered or underwent a
      surgical excision. CONCLUSION: Alcohol sclerosing therapy administered in the
      clinic setting without alcohol is not an effective treatment in the nonoperative
      management of painful interdigital neuromas and has been abandoned in our clinic.

PMID- 21733419
TI  - Pantalar arthrodesis for post-traumatic arthritis and diabetic neuroarthropathy
      of the ankle and hindfoot.
AB  - BACKGROUND: Pantalar arthrodesis is an important salvage option for stabilizing
      the hindfoot and salvaging the limb following trauma or collapse. This report
      evaluates the healing rates and complications which occur in diabetics and post
      traumatic patients. MATERIALS AND METHODS: Twenty patients presenting with post
      traumatic arthritis of the ankle-hindfoot (twelve) or with Type II or Type IIIA
      Charcot arthropathy (eight) were managed with a pantalar fusion. Followup
      averaged 46 months. Patients were evaluated using the Short Form-36 (SF-36), the
      American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score, the
      Short Musculoskeletal Function Assessment (SMFA) and the Visual Analog Pain Scale
      (VAS). RESULTS: There were no amputations in either group. Casting averaged 14.9
      weeks, full weightbearing was achieved at 25.1 weeks and time to union averaged
      44.1 weeks. Average age was 56.3 yrs. and BMI averaged 34.2. Fourteen patients
      (70%) had their surgery performed in multiple stages. Acceptable outcomes were
      noted for all patients for the SF-36, AOFAS and SMFA scores. VAS scores averaged
      2.2. There were ten complications (50%); four patients (two in each group)
      required additional surgery. CONCLUSIONS: Pantalar arthrodesis is a reasonable
      salvage option for patients with severe post traumatic arthropathy and
      neuropathic arthropathy. Patients should be informed of the increased risks as
      well as the long periods of postoperative immobilization and nonweightbearing. We
      believe a pantalar arthrodesis can produce acceptable outcomes regardless of the
      cause of disability, with a staged or single approach, and whether the surgery is
      performed with plates and screws or an intramedullary device.

PMID- 21733420
TI  - First ray resection arthroplasty versus arthrodesis in the treatment of the
      rheumatoid foot.
AB  - BACKGROUND: Different options exist for the operative treatment of forefoot
      problems and deformities in rheumatoid arthritis (RA). The current study compared
      first ray and resection arthroplasty with respect to patient satisfaction,
      clinical and functional outcome. MATERIALS AND METHODS: In a retrospective study
      53 RA patients were investigated with a minimum followup of 2 years after
      corrective forefoot surgery. Two patient groups were distinguished: One group had
      been treated with arthrodesis of the first metatarsophalangeal (MTP) joint
      whereas the other group had been treated with a first ray resection arthroplasty.
      Both groups underwent resection arthroplasty at the lesser metatarsal heads. Our
      arthrodesis patients were significantly younger than patients with resection
      arthroplasty. Five patients had been treated bilaterally so that the results of
      58 feet were analyzed. RESULTS: Patient satisfaction was lower in the arthrodesis
      group as compared to the resection arthroplasty patients. However, the
      arthrodesis patients revealed better functional results and showed a push-off
      from the hallux. No significant radiographic difference was seen in the mean
      hallux valgus angles. Younger patients revealed a higher disease activity and a
      worse general health status than older patients. Pedobarographic results
      demonstrated significant differences in selected foot regions, predominantly in
      the hallux. Peak pressures were significantly higher in the lateral midfoot and
      the hallux after arthrodesis as compared to the resection arthroplasty group.
      CONCLUSION: Patients with arthrodesis revealed better foot function during the
      dynamic roll-over process even though the resection arthroplasty patients were
      subjectively more satisfied.

PMID- 21733421
TI  - Ankle tourniquet pain control in forefoot surgery: a randomized study.
AB  - BACKGROUND: Forefoot surgery is often performed under regional anesthesia in
      awake patients, using tourniquet or Esmarch bandage to obtain a bloodless field.
      The purpose of this study was to examine the value and need for local tourniquet
      pain control using local subcutaneous analgesic mixture in patients undergoing
      forefoot surgery under ankle block anesthesia. MATERIALS AND METHODS: We
      prospectively randomized 56 patients who underwent forefoot surgery under ankle
      block to receive either subcutaneous local anesthetic mixture under the
      tourniquet or no additional anesthetic. We checked for local tourniquet pain
      score (VAS 0 to 100) and skin condition during and after the procedure. RESULTS:
      The tourniquet was quite tolerable in both groups, with an average VAS score of 7
      to 21. No difference was observed between groups throughout most of the
      procedure. No correlation between VAS scores and procedure length or patient's
      age or gender was found. CONCLUSION: An ankle tourniquet was well-tolerated by
      patients without need for local anesthetic beneath the cuff.

PMID- 21733422
TI  - Operative fixation of unstable ankle fractures in patients aged over 80 years.
AB  - INTRODUCTION: Controversy exists regarding the surgical treatment of unstable
      ankle fractures in the very elderly age group of over 80 years. However, the
      literature regarding the prognosis of surgery in this elderly group is limited.
      The purpose of our study was to evaluate the results of patients above 80 years
      old who underwent operative fixation for unstable ankle fractures. MATERIALS AND
      METHODS: Ninety-two consecutive patients, 80 females and 12 males, above 80 years
      of age had open reduction and internal fixation for unstable ankle fractures
      during the period of January 1998 to August 2007. The data was collected
      retrospectively from the case records and radiographs. The complications were
      noted and the risk factors for poor outcome were analyzed. The average age was
      85.2 (range, 80.1 to 95.1) years. The minimum duration of followup was 9 months,
      with an average of 15 (range, 9 to 28) months. RESULTS: The most common fracture
      pattern was Danis-Weber B type. The superficial wound infection rate was 7% (6
      cases) and the deep infection rate was 4.6% (4 cases). The 30 day postoperative
      mortality was 5.4% (five cases). Eighty-six percent (75 out of 87 cases) were
      able to return back to their pre injury mobility at the last followup. Diabetes,
      dementia, peripheral vascular disease and smoking were found to be statistically
      significant risk factors associated with wound complications. CONCLUSION: The
      results of operative fixation of unstable ankle fractures were encouraging with
      good functional recovery and return to pre injury mobility status in most cases.

PMID- 21733423
TI  - Closed intramedullary screw fixation for nonunion of fifth metatarsal Jones
      fracture.
AB  - BACKGROUND: Nonunion following a proximal fifth metatarsal metaphyseal-diaphyseal
      or Jones fracture can cause considerable pain with high morbidity and loss of
      work. Treatment should aim for early union, thus allowing early return to
      activity. The present study evaluated the outcomes and the time required for
      union following closed intramedullary screw fixation for this condition.
      MATERIALS AND METHODS: Between January 2005 to August 2009, 14 patients were
      diagnosed with nonunion following a Jones fracture. Mean age at surgery was 49
      years. Mean duration from injury to surgery was 28 weeks. All nonunions were
      fixed with a single intramedullary screw inserted from the base of the fifth
      metatarsal without opening the nonunion site. Serial postoperative radiographs
      were evaluated to determine union. Time required for return to activity was
      determined. Outcome was assessed with help of pain scores. Mean followup was 27
      months. RESULTS: Union was achieved in all 14 patients with one delayed union.
      Mean time to union was 13.3 (range, 8 to 20) weeks. All patients were able to
      start unassisted full weightbearing without pain at mean 10.2 weeks. Overall pain
      score improved from a preoperative mean of 5.4 to postoperative mean of 1.0.
      Complications included one deep infection, one delayed wound healing and one
      sural neuroma. CONCLUSION: Closed intramedullary screw fixation achieved an
      excellent union rate when used in the treatment of nonunion of a Jones fractures.

PMID- 21733424
TI  - Effect of supramalleolar varus and valgus deformities on the tibiotalar joint: a
      cadaveric study.
AB  - BACKGROUND: Distal tibia coronal plane malalignment predisposes the ankle joint
      to asymmetric load. The purpose of this cadaveric study was to quantify changes
      in pressure and force transfer in an ankle with a supramalleolar deformity.
      MATERIALS AND METHODS: Seventeen cadaveric lower legs were loaded with 700 N
      after creating supramalleolar varus and valgus deformities. The fibula was left
      intact in 11 specimens and osteotomized in six. Tekscan(c) sensors were used to
      measure the tibiotalar pressure characteristics. RESULTS: In isolated
      supramalleolar deformity, the center of force and peak pressure moved in an
      anteromedial direction for valgus and posterolateral direction for varus
      deformities. The change was in an anteromedial direction for varus and in a
      posterolateral direction for valgus deformities in specimens with an osteotomized
      fibula. CONCLUSION: Two essentially different groups of varus and valgus
      deformities of the ankle joint need to be distinguished. The first group is an
      isolated frontal plane deformity and the second group is a frontal plane
      deformity with associated incongruency of the ankle mortise. CLINICAL RELEVANCE:
      Our findings underline the complexity of asymmetric osteoarthritis of the ankle
      joint. In addition, results from this study provide useful information for future
      basic research on coronal plane deformity of the hindfoot and for determining
      appropriate surgical approaches.

PMID- 21733425
TI  - Limitations of standard fluoroscopy in detecting rotational malreduction of the
      syndesmosis in an ankle fracture model.
AB  - BACKGROUND: When treating ankle fractures with associated syndesmosis injury,
      failure to anatomically reduce the syndesmosis may lead to poor outcome. While
      shortening and posterior subluxation of the distal fibula are readily detected by
      intraoperative fluoroscopy, it is unclear how well malrotation can be assessed.
      The ability of fluoroscopy to detect rotational malreduction of the fibula was
      the subject of this study. MATERIALS AND METHODS: Distal fibula fractures with
      complete syndesmotic injury were produced in ten cadaveric ankles. Two Kirschner
      wires were used to fix the fibula in neutral (0 degrees), 10 to 30 degrees of
      external rotation (ER), and 10 degrees to 30 degrees of internal rotation (IR).
      Using C-arm fluoroscopy tibio-fibular clear space and tibio-fibular overlap in
      the AP and mortise views, and posterior fibular subluxation in the lateral view
      were measured to assess reduction of the syndesmosis. RESULTS: The radiographic
      indices were able to detect as little as 10 degrees of IR but were within their
      normal range in up to 30 degrees of ER. When assessing for a 2mm difference
      compared to the intact ankle, sensitivity of all indices were low after more than
      15 degrees ER, but high and clinically useful after more than 15 degrees of IR.
      CONCLUSION: Radiographic indices for syndesmosis disruption could not detect ER
      malreduction of the syndesmosis of up to 30 degrees. CLINICAL RELEVANCE: In the
      setting of ankle fractures with syndesmosis disruption, fixing the fibula in as
      much as 30 degrees of external rotation may go undetected using intraoperative
      fluoroscopy alone.

PMID- 21733426
TI  - Medial longitudinal arch deformation during walking and stair navigation while
      carrying loads.
AB  - BACKGROUND: Understanding the biomechanics of the medial longitudinal arch (MLA)
      may provide insights into injury risk and prevention, as well as function of the
      arch-supporting structures. Our understanding of MLA deformation is currently
      limited to sit-to-stand, walking, and running. MATERIAL AND METHODS: Three
      dimensional deformation of the MLA of the right foot was characterized in 17
      healthy participants during several simulated activities of daily living. MLA
      deformation was quantified by both changes in arch length and navicular
      displacement during the stance phase of three motions: walking, stair ascent, and
      stair descent. Three levels of load were also evaluated: no load, a front load
      (13.6 kg), and a backpack load (13.6 kg). Force platforms and an eight-camera
      motion capture system were used to collect relevant lower extremity kinetic and
      kinematic data. RESULTS: Motion type had a significant (p < 0.05) effect on
      navicular displacement and arch length elongation with navicular displacement
      being greatest during stair descent, while the walking and stair descent
      conditions showed the greatest increase in arch length. External load did not
      significantly affect either of these two measures (p > 0.05). CONCLUSION:
      Differences in the MLA deformation variables resulting from varied dynamic
      activities of daily living can be greater than those during walking and should be
      considered. CLINICAL RELEVANCE: Detailing the mechanics of the MLA may aid in
      further understanding injuries associated with the MLA, and the results of the
      current study indicate that these mechanics change based on activity.

PMID- 21733427
TI  - Anterolateral and medial locking plate stiffness in distal tibial fracture model.
AB  - BACKGROUND: The purpose of this study was to compare the axial and torsional
      stiffness between anterolateral and medial distal tibial locking plates in a
      pilon fracture model. MATERIALS AND METHODS: The biomechanical stiffness of
      anterolateral or medial plated pilon fracture models was evaluated. Six Sawbones
      Composite Tibiae with a simulated pilon fracture representing varus or valgus
      comminution (OTA 43-A2.2) were plated with a Synthes 3.5-mm contoured LCP
      anterolateral or medial locking distal tibia plate. Load as a function of axial
      displacement and torque as a function of angular displacement were recorded. Each
      tibia was tested with a fracture wedge in place and removed with a medial and
      then anterolateral plate. RESULTS: Loading the tibial plateau medial to the
      central axis, no significant difference in mean stiffness between the
      anterolateral and medial plates was demonstrated with the fracture wedge in
      place. A significant difference was demonstrated with the wedge removed. Loading
      the plateau posterior to the central axis, no significant difference in mean
      stiffness between plates was demonstrated with the wedge in place or removed.
      With the wedge in place, there was a significant difference in mean torsional
      stiffness for clockwise rotation, but not counterclockwise rotation. With the
      wedge removed, no significant difference appeared in mean stiffness for clockwise
      and counterclockwise rotation. CONCLUSION: Distal tibia extra-articular fractures
      stabilized with anterolateral or medial locking plate constructs demonstrated no
      statistically significant difference in biomechanical stiffness in compression
      and torsion testing. CLINICAL RELEVANCE: We believe this study indicates the
      primary concern when treating a pilon fracture may be soft-tissue considerations.
      Further clinical studies are required before definitive changes can be
      recommended regarding pilon fracture fixation.

PMID- 21733428
TI  - Calcific tendinitis of the peroneus longus: case report.

PMID- 21733429
TI  - Syndactyly with hallux valgus: a case report.

PMID- 21733430
TI  - Bicortical structural autograft harvest during medializing calcaneal osteotomy:
      technique tip.

PMID- 21733431
TI  - Endoscopic debridement of the Achilles insertion, bursa, and the calcaneal
      tubercle with an accessory postero-lateral portal: technique tip.

PMID- 21733432
TI  - Calcaneal traction pin placement simplified: a cadaveric study.
AB  - BACKGROUND: The tibial neurovascular bundle and sural nerve are at risk with
      errant pin placement during transcalcaneal pin placement. The purpose of this
      study was to determine a relative safe zone using a single osseous landmark to
      establish a technique applicable in the presence of trauma. We describe the
      neural anatomy anatomically and radiographically, giving surgeons a reliable and
      relatively safe technique for transcalcaneal pin placement. MATERIALS AND
      METHODS: Twenty-four cadavers were dissected for the major medial neurovascular
      structures and the sural nerve. The closest distance from the neurovascular
      structures to the posterior inferior calcaneus was measured. RESULTS: The mean
      distance from the posterior inferior calcaneus to the closest major medial
      neurovascular structure was 3.4 cm (SD +/- 0.36; range, 2.6 to 4.1 cm). The mean
      distance to the sural nerve was 3.4 cm (SD +/- 0.54; range, 2.3 to 4.6 cm).
      According to the 95% confidence intervals, a relative safe zone of 3.1 cm as a
      radius from the posterior inferior calcaneus was determined. CONCLUSION: A
      relatively safe zone of 3.1 cm based on 95% confidence intervals as described as
      a radius from the posterior inferior calcaneus can be used for transcalcaneal pin
      placement in most cases without injury to the medial neurovascular bundle or
      sural nerve. However anatomic variation may result in the neurovascular bundle
      being within this zone. CLINICAL RELEVANCE: We describe a surgical technique for
      reliable placement of a transcalcaneal pin within this relative safe zone and a
      safe distance from the closest neurovascular structure.

PMID- 21733434
TI  - Epidemiology and outcomes of acute Achilles tendon rupture with operative or
      nonoperative treatment using an identical functional bracing protocol.
AB  - BACKGROUND: This study reports on the demographics of acute Achilles tendon
      rupture in our region and compares the results of a selective approach to
      operative and nonoperative treatment using an identical rehabilitation program
      with functional bracing. MATERIALS AND METHODS: A consecutive series of 363
      patients, aged 15 to 60 years, treated over 8.5 years by either open operative
      repair (143) or nonoperatively (220) were compared with respect to demographics,
      re-rupture rate, and major wound complication. RESULTS: There was an almost equal
      number of males (159) and females (152) up to age 50 years but males comprised
      73% of patients aged 51 to 60 years. Netball was the most common cause of injury
      and explains the relatively high incidence in females. In the 143 patients
      treated surgically there were two re-ruptures (1.4%) and two reoperations for
      wound complications (1.4%). In the 220 patients treated nonoperatively there were
      19 re-ruptures (8.6%), 13 of 113 males (11.5%) and six of 107 females (5.6%).
      There was a significantly lower re-rupture rate, and reoperation rate in the
      surgical group (p < 0.05). In the nonoperative group there was a significantly
      lower rate of re-rupture in patients over 40 (six of 119) (4.1%) compared with
      those 40 years and under (13 of 99, 13.1%) and between females over 40 when
      compared with males 40 years and under. CONCLUSION: In our region there is a high
      incidence of Achilles tendon rupture among women due to netball and results in a
      younger age of injury than previously reported. Our results support surgery in
      patients less than 40 years, particularly males, if there are no
      contraindications. Functional bracing as part of nonoperative treatment can
      result in low re-rupture rates in patients over 40, especially in females.

PMID- 21733435
TI  - Prospective, randomized, multi-center feasibility trial of rhPDGF-BB versus
      autologous bone graft in a foot and ankle fusion model.
AB  - BACKGROUND: The increased morbidity and surgical time associated with harvesting
      autologous bone graft (ABG) have encouraged surgeons to develop synthetic
      orthobiologic alternatives. The recombinant form of platelet-derived growth
      factor (rhPDGF-BB), an angiogenic, mitogenic, and chemotactic cytokine, has been
      shown to significantly enhance bone formation in human periodontal osseous
      defects when combined with a tricalcium phosphate carrier (beta-TCP). The purpose
      of this prospective, controlled, randomized, multi-center feasibility clinical
      trial was to compare the safety and efficacy of this biosynthetic bone graft
      substitute (AugmentTM Bone Graft) to ABG during ankle and hindfoot fusion.
      MATERIALS AND METHODS: Twenty adult subjects requiring ankle or hindfoot fusion
      from three U.S. centers were enrolled and randomized in a 2:1 ratio to receive
      AugmentTM or ABG, respectively. Surgical approach and fixation techniques were
      standardized, and minimum followup was 9 months. The primary endpoint was
      radiographic osseous union, evaluated by a blinded independent radiologist.
      Secondary endpoints included assessment of clinical success, union rate by serial
      computed tomography (CT) examination, time to full weightbearing, AOFAS Ankle
      Hindfoot Score (AOFAS), Foot Function Index (FFI), Short Form-12 (SF-12), and
      Visual Analog pain assessment Scale (Pain VAS). RESULTS: At 36 weeks, 77% (10/13)
      of the AugmentTM and 50% (3/6) of the ABG patients were fused based on
      radiographic criteria. There were two nonunions in the AugmentTM group (9%,
      2/14). Healing rates based on 12 week CT scanning (50% osseous bridging) were 69%
      (9/13) in the AugmentTM and 60% (3/5) in the ABG groups, respectively. All
      functional outcome measures (FFI, AOFAS, SF-12), as well as the VAS pain scores,
      improved in both groups over time. Surgical procedure times lasted an average 26
      minutes longer for the ABG as compared to the AugmentTM populations. There were
      no device related serious adverse events in this study. CONCLUSION: Based on the
      available data, the rate of radiographic union, time to full weightbearing, and
      outcomes scores between the AugmentTM and ABG subjects appear comparable.
      AugmentTM may represent a safe and efficacious treatment alternative to ABG
      during foot and ankle arthrodesis.

PMID- 21733436
TI  - Outcomes following midfoot arthrodesis for primary arthritis.
AB  - BACKGROUND: Primary midfoot arthritis is a disabling painful condition of the
      foot. The aim of the study was to assess the functional outcomes following
      midfoot arthrodesis for primary midfoot arthritis. MATERIALS AND METHODS: Between
      2000 and 2006, 95 patients (104 feet) underwent midfoot arthrodesis for primary
      midfoot arthritis. Midfoot collapse, if present, was corrected at the time of
      arthrodesis. Mean age at surgery was 62 years. Gastrocnemius contracture was seen
      in 81 (78%) feet and was treated with a recession. Radiographs were reviewed for
      correction of deformity. Complications and reoperations were noted. Outcome
      evaluation included pain, American Orthopaedic Foot Ankle Society (AOFAS) midfoot
      score and patient satisfaction. Outcomes were available in 68 patients (74 feet)
      with mean followup of 56 (range, 24 to 102) months. RESULTS: We achieved union in
      96 out of 104 feet (92 %). There was one delayed union and eight nonunions. Major
      complications (4/104, 4%) included three deep infections and one chronic regional
      pain syndrome. Reoperations were required in 11 feet in addition to 26
      symptomatic hardware removals. Radiographs showed a significant improvement in
      the talo-first metatarsal angle and medial cuneiform height. Pain improved from
      preoperative mean of 7 +/- 2 to postoperative mean of 2 +/- 2. AOFAS score
      improved from preoperative mean of 32 (range, 25 to 43) to postoperative mean of
      79 (range, 65 to 90). Ninety percent of patients were satisfied with the final
      result. CONCLUSION: Primary or degenerative arthritis of the midfoot with
      refractory symptoms was treated with midfoot arthrodesis with good results and a
      low incidence of nonunion.

PMID- 21733437
TI  - Role of intraoperative varus stress test for lateral soft tissue release during
      chevron bunion procedure.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical results of
      distal chevron osteotomy performed in conjunction with selective lateral soft
      tissue release. The criterion for doing a lateral soft tissue release was
      assessed by determining the ease and completeness of passive hallux valgus
      correction at the time of surgery. MATERIALS AND METHODS: Between August 2005 and
      November 2007, 48 feet in 43 patients classified as having mild to moderate
      hallux valgus were retrospectively studied. Distal chevron osteotomy without
      lateral soft tissue release was performed in 26 cases (Group 1) when passive
      correction of the hallux valgus deformity was possible. Distal chevron osteotomy
      with lateral soft tissue release was performed in 22 cases (Group 2) when passive
      correction was not possible. Average followup was 23 (range, 12 to 28) months.
      Clinical results were assessed using radiographic parameters [hallux valgus angle
      (HVA), first and second intermetatarsal angle (1,2 IMA)], AOFAS scale and
      patient's subjective satisfaction. RESULTS: For Group 1: the average correction
      of HVA was 12.8 degrees, the average correction of IMA was 4.7 degrees, and the
      AOFAS score improved an average of 29.2 points at the last followup. Thirteen
      patients were very satisfied and ten patients were satisfied with the results. No
      patient was dissatisfied. For Group 2: the average correction of HVA was 19.1
      degrees, the average correction of IMA was 7 degrees and AOFAS score improved at
      an average of 31.8 points at the last followup. Twelve patients were very
      satisfied, seven patients were satisfied and one patient, who had stiffness of
      the first metatarsophalangeal joint, was dissatisfied with the result.
      CONCLUSION: Distal chevron osteotomy with selective lateral soft tissue release
      based on the ability to passively correct the hallux valgus deformity lead to
      safe and stable correction.

PMID- 21733438
TI  - Functional outcome of matrix-associated autologous chondrocyte implantation in
      the ankle.
AB  - BACKGROUND: The technique of Matrix-associated autologous chondrocyte
      implantation (MACI) is well established with satisfactory outcomes up to 5 years
      in the knee. Fewer series describe the outcomes of this technique in the ankle.
      We present the functional outcomes of the technique for a single surgeon series
      in a general hospital setting. MATERIALS AND METHODS: Twenty-seven patients, mean
      age 41, were reviewed at 3.7 (range, 1 to 5) years. Patients were assessed using
      the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scale, Tegener
      activity score and University of California lower extremity activity scale. MRI
      findings were also reviewed. RESULTS: While most patients report a significant
      improvement in symptoms with full return to activities of daily living, 36% of
      those under 40 and 78% of those over 40 reported restricted recreational
      activity. Of the patients under 40 years of age, 86% were able to run compared
      with 23% of those over 40. Of patients over 40, 64% continued to have moderate or
      severe pain. CONCLUSION: Careful preoperative counseling is required for patients
      of all ages regarding likely outcomes. In patients over 40, the procedure is
      unlikely to give good pain relief and alternative options should be considered.

PMID- 21733439
TI  - Noninsertional Achilles tendinopathy treated with gastrocnemius lengthening.
AB  - BACKGROUND: Surgery is frequently considered an option for refractory,
      symptomatic noninsertional Achilles tendinopathy. Gastrocnemius equinus can
      result in mechanical overload of the Achilles tendon and may be a factor in its
      etiology. Our hypothesis was that reducing load transmission to the Achilles
      tendon by gastrocnemius lengthening (Strayer procedure) may be an effective
      treatment. MATERIALS AND METHODS: A prospective case series of all patients with
      a minimum 1-year symptomatic noninsertional Achilles tendinopathy who underwent
      gastrocnemius lengthening was evaluated before surgery, and at 1 and 2 years
      after surgery. There were 14 patients (17 tendons). RESULTS: One year after
      surgery, the median American Orthopaedic Foot and Ankle Society (AOFAS) Ankle
      Hindfoot score was 100 points, as compared to 71 points preoperatively (p <
      0.001). The median total Foot Function Index (FFI) decreased significantly from
      39 to 12 points at 1 year (p < 0.001) and remained stable (12 points) at 2 years.
      An electronic goniometer recorded a mean gain in ankle dorsiflexion of 13
      degrees. At 1 year after surgery the MRI in all eight patients (ten tendons) with
      a preoperative MRI demonstrated a decrease in signal hyperintensity and tendon
      size, signifying an improvement of the tendinopathy. At 2 years after surgery,
      patient satisfaction assessment revealed that all but one patient was satisfied
      with the result and 11 of the 14 (79%) patients were able to resume their
      previous sporting activities. There were no complications. CONCLUSION:
      Gastrocnemius lengthening was an effective treatment for chronic Achilles
      noninsertional tendinopathy. Two-year results show good to excellent clinical
      outcome.

PMID- 21733440
TI  - Radiographic analysis of wedge allograft correction of angular malalignment in
      ankle fusion.
AB  - BACKGROUND: Patients undergoing ankle arthrodesis often have coronal or sagittal
      plane malalignment. Correction of this deformity can be technically challenging.
      This retrospective review examines the use of an augmented interposition wedge
      allograft for deformity correction in ankle arthrodesis. MATERIALS AND METHODS:
      Nineteen patients underwent open ankle arthrodesis with interposition allograft
      at our institution since 2003. Sixteen patients had isolated ankle fusions and
      three patients had ankle fusions as part of a tibiotalocalcaneal fusion. A wedge
      of frozen tricortical iliac crest or femoral head allograft was cut to
      appropriate size and shape to correct angular deformity with an average maximum
      graft width of 9.5 mm. Fixation of the arthrodesis was with either a cannulated
      screw and plate construct or a lateral blade plate. Radiographs were reviewed to
      assess preoperative, initial postoperative and final alignment at the time of
      solid fusion. Fusion was assessed on plain radiographs by visualization of
      bridging bony trabeculae. RESULTS: Seventeen of 19 patients (89%) obtained fusion
      at an average of 14.9 wks. Eleven ankles had preoperative tibiotalar valgus
      deformity with an average coronal alignment of 98.8 degrees and sagittal
      alignment of 110.5 degrees. Final coronal alignment was 90.9 degrees and sagittal
      alignment was 107.7 degrees. Eight ankles had varus deformity with an average
      coronal alignment of 77.4 degrees and sagittal alignment of 101.9 degrees. Final
      coronal alignment was 89.4 degrees and sagittal alignment was 107.4 degrees.
      CONCLUSION: The tibiotalar joint fusion rate in this series compares favorably to
      historically published data for standard ankle fusion. Interposition allograft
      was an effective method for deformity correction in difficult ankle arthrodeses.

PMID- 21733441
TI  - Surgeon practices regarding operative treatment of posterior malleolus fractures.
AB  - BACKGROUND: Operative indications for surgical treatment of posterior malleolar
      fractures associated with fractures of the distal fibula and tibia are not
      currently well defined. The purpose of the present study was to determine the
      current practice among orthopaedic surgeons regarding the management of posterior
      malleolus fractures. MATERIALS AND METHODS: Web-based questionnaires were emailed
      to members of the Orthopaedic Trauma Association (OTA) and American Orthopaedic
      Foot and Ankle Society (AOFAS). Requested information included demographics and
      treatment preferences for five clinical scenarios with different fracture
      characteristics. Four hundred one respondents completed the survey (20% response
      rate). Ninety eight (24%) subjects had received specialty training in orthopaedic
      trauma, 199 (50%) in foot and ankle (F&A) surgery and six (2%) in both
      orthopaedic trauma and F&A surgery. Ninety five (24%) had either no or other
      specialty training. RESULTS: The most frequently reported indication for fixation
      was not based on a fragment size threshold, but rather was ''depends on stability
      and other factors'' (56%). Trauma surgeons, those with less than 10 years
      experience, and those who treated more than five ankles fractures per month were
      significantly more likely to use factors other than size for indications (p =
      0.026, <0.01, and <0.01, respectively). Despite this general response, fragment
      size still affected treatment decisions. A fragment comprising 50% of the
      articular surface was indicated for fixation by 97% of respondents, while a size
      of 10% would be treated by only 9% of respondents. For a posterior fragment with
      20% articular involvement and a small free osteochondral fragment, fixation was
      deemed necessary by 44% of respondents. There were no differences in fellowship
      training, years of experience in practice, or ankle fracture volume per month in
      these three situations. A larger proportion of trauma trained surgeons considered
      fixation necessary compared to F&A trained surgeons in this case (p = 0.028).
      When posterior malleolus fixation was indicated for a large fragment, direct open
      reduction using the flexor hallucis longus -peroneal tendon interval was the most
      commonly selected approach in all cases. Trauma-trained surgeons were
      significantly more likely to choose antiglide plate fixation compared to screw
      only fixation (p < 0.05). CONCLUSION: In this survey study of trauma and F&A
      surgeons, significant variation existed regarding most aspects of posterior
      malleolar ankle fracture treatment. Most notably, factors other than fragment
      size most impacted surgical indications. Newer techniques such as direct exposure
      and plating of the posterior malleolus are chosen more frequently than
      traditional techniques of indirect reduction and percutaneous screw fixation.

PMID- 21733442
TI  - Corticosteroid injections in the treatment of foot & ankle disorders: an AOFAS
      survey.
AB  - BACKGROUND: Evidence-based guidelines for the use of injectable corticosteroids
      are lacking, and the true incidence of complications is unknown. MATERIALS AND
      METHODS: The 2007--2008 AOFAS membership (969 members) was electronically queried
      to identify corticosteroid injection practices for certain clinical entities and
      rates of complications. One hundred ninety-seven surveys were returned. Eleven
      clinical diagnoses were evaluated for number of injections per year per
      respondent, rate of injection, plans to change injection pattern, and use of
      immobilization. Thirteen possible complications were analyzed for observed
      frequencies and total number of complications. RESULTS: Those in practice less
      than 5 years showed the lowest rate of injections at 14.1 per month, which
      increased to 26.1 for those in practice 6 to 10 years. An overall average of 20.6
      injections per month per clinician was reported. Injections for midsubstance
      Achilles tendinopathy was largely avoided as demonstrated by a 98% no-inject
      rate. Insertional Achilles tendonitis was similar, albeit lower with an 88% no
      inject rate. Non-Achilles tendonitis showed a varied response for injections.
      Posterior tibial tendonitis was injected 26% of the time, whereas peroneal
      tendonitis was injected 54% of the time. Complications including skin
      depigmentation were observed most frequently (5.1%), followed by atrophy (4%),
      flare reaction (3.5%), MTPJ dislocation (2.7%), plantar fascia rupture (1.5%),
      and heel pad atrophy (1.4%). CONCLUSION: Despite many case reports of
      complications, our survey indicates that the incidence of complications was
      perceived to be low and generally related to the injection site (skin
      depigmentation, atrophy, flare reaction).

PMID- 21733443
TI  - Surgical treatment of advanced hallux rigidus by interpositional arthroplasty.
AB  - BACKGROUND: While arthrodesis is the gold-standard for end-stage hallux rigidus,
      it leads to loss of mobility. The purpose of this paper was to report our
      clinical results with modified interpositional arthroplasty for the treatment of
      advanced (Grade III and IV of Coughlin and Shurnas) hallux rigidus. MATERIAL AND
      METHODS: Twenty-five feet with Grade III and IV hallux rigidus underwent
      cheilectomy, minimal proximal phalanx resection (modified Keller) and
      interposition of the dorsal capsule and EHB. RESULTS: At a minimum followup of 15
      months, the mean postoperative hallux AOFAS score was 93.6 points with a pain
      subscore of 36.4 (maximum, 40 points) and functional subscore of 42.5 (maximum,
      45 points). Subjectively, patients were completely satisfied with the surgical
      outcome in 75% of the cases. CONCLUSION: The modified interpositional
      arthroplasty was a feasible surgical option to address advanced hallux rigidus in
      middle aged patients.

PMID- 21733444
TI  - Influence of stretching and warm-up on Achilles tendon material properties.
AB  - BACKGROUND: Controversy exists on stretching and warm-up in injury prevention. We
      hypothesized that warm up has a greater effect on Achilles tendon biomechanics
      than static stretching. This study investigated static stretching and warm-up on
      Achilles tendon biomechanics in recreational athletes, in vivo. MATERIALS AND
      METHODS: Ten active, healthy subjects, 5 males, 5 females, With a mean age of
      22.9 years with no previous Achilles tendon injuries were recruited. Typical
      stretching and warm-up routines were created. Testing was performed in a
      randomized cross-over design. A custom-built dynamometer was utilized to perform
      controlled isometric plantarflexion. A low profile ultrasound probe was utilized
      to visualize the musculotendinous junction of the medial gastrocnemius. An eight
      camera motion capture system was used to capture ankle motion. Custom software
      calculated Achilles tendon biomechanics. RESULTS: Achilles tendon force
      production was consistent. No statistically significant differences were detected
      in stretch, stiffness, and strain between pre-, post-stretching, and post-warm-up
      interventions. CONCLUSION: Stretching or warm-up alone, and combined did not
      demonstrate statistically significant differences. Stretching and warm-up may
      have an equivalent effect on Achilles tendon biomechanics. Prolonged and more
      intense protocols may be required for changes to occur. CLINICAL RELEVANCE:
      Stretching and warm-up of the Achilles before exercise are commonly practiced.
      Investigating the effect of stretching and warm-up may shed light on potential
      injury prevention.

PMID- 21733445
TI  - Stabilization of chevron bunionectomy with a capsuloperiosteal flap.
AB  - BACKGROUND: Distal chevron osteotomy (DCO) for mild to moderate hallux valgus
      deformity is inherently more stable than the other forms of distal metatarsal
      osteotomy, but complications such as loss of correction, infection, joint
      stiffness, delayed union, malunion and nonunion can occur. In this study, we
      evaluated the use of a capsuloperiosteal flap for stabilization of DCO in the
      treatment of hallux valgus. MATERIALS AND METHODS: A retrospective study was
      conducted on 59 patients (88 feet) that underwent distal Chevron osteotomy
      stabilized only with a capsuloperiosteal flap for mild and moderate hallux valgus
      deformity with a mean followup of 11.3 years. Clinical evaluation was calculated
      using the hallux score of the American Orthopaedic Foot and Ankle Society
      (AOFAS). RESULTS: The score improved from a preoperative mean of 52 to a mean of
      91.5 points at last followup. Average hallux valgus angle changed from 30.3
      degrees preoperatively to 14.2 degrees postoperatively at the last followup.
      Intermetatarsal angle 1-2 changed from 13.6 degrees preoperatively to 10.2
      degrees postoperatively. The correction proved to be consistent with only an
      average of 3.4-degree correction loss and 4.9-degree loss in the range of motion.
      Eighty-six feet (97.7%) were pain free. Discomfort with shoewear was absent in 84
      feet (95.5%) postoperatively and 24 of 25 (96%) patients were satisfied
      cosmetically. CONCLUSION: Capsuloperiosteal flap stabilization of distal chevron
      osteotomy for mild-moderate hallux valgus yielded excellent clinical results at
      long-term followup.

PMID- 21733446
TI  - Analysis of the proximal phalanx size as a guide for an Akin closing wedge
      osteotomy.
AB  - BACKGROUND: The Akin closing wedge osteotomy for correction of hallux valgus
      interphalangeus has experienced a resurgence in popularity. Commonly, the size of
      the osteotomy is visually judged intraoperatively. We present a means of
      performing the osteotomy more objectively. MATERIALS AND METHODS: Radiographs of
      101 feet were studied to derive mean values for dimensions of the hallux proximal
      phalanx in the general population. Based on these we calculated the size of
      osteotomy required for given corrections. RESULTS: The mean hallux width 5 mm
      distal to the apex of the articular surface differed between males and females.
      In males the mean width was 18 mm (95% CI 17.5 to 18.8) and in females 15 mm (95%
      CI 14.5 to 15.5). For a 10 degree correction, an osteotomy with a 3 mm base would
      be required. CONCLUSION: Although the Akin osteotomy dimensions are commonly
      estimated, a more objective method of planning the osteotomy is presented. The
      method can also be applied to any closing wedge osteotomy. CLINICAL RELEVANCE: We
      believe this method of the Akin osteotomy can improve the accuracy of the
      surgery.

PMID- 21733447
TI  - A biomechanical analysis of a tensioned suture device in the fixation of the
      ligamentous Lisfranc injury.
AB  - BACKGROUND: We hypothesized that using a cadaveric Lisfranc ligamentous injury
      model, abduction stress would provoke greater post-injury motion than axial
      weightbearing between the medial cuneiform (MC1) and the base of the second
      metatarsal (MT2). Second, we hypothesized that both a tensioned suture-button
      device and a rigid screw fixation method could maintain a reduction and similarly
      restrain motion to intact (pre-injury) levels. MATERIALS AND METHODS: Motion was
      measured between MC1 and MT2 in five matched pairs of human cadaveric feet.
      Specimens were tested prior to injury, following a transverse ligamentous
      Lisfranc injury, and then randomized to either screw or tensioned suture-button
      fixation. Axial then abduction loads were applied. Measurements were repeated
      after one thousand loading cycles. RESULTS: With both axial and abduction loads,
      statistically significant differences in motion were detected between the intact
      and post-injury conditions, although the magnitudes were greater with abduction
      (6.8 mm versus 2.0 mm, p = 0.000004). With abduction loads, both fixation methods
      were effective in restraining motion to pre-injury levels (screw fixation: 1.5 mm
      intact versus 1.1 mm post-fixation, p = 0.487; suture-button fixation: 1.3 mm
      intact versus 2.1 mm post-fixation, p = 0.063), and similarly, both devices
      restrained motion to less than post-injury levels (screw fixation: 8.1 mm post
      injury versus 1.1 mm post-fixation, p = 0.001; suture-button fixation: mean 5.5
      mm post-injury versus 2.1 mm post-fixation, p = 0.0002). No significant
      differences in these patterns were detected following cyclic loading. CONCLUSION:
      Small, though statistically significant, amounts of motion are produced between
      MC1 and MT2 with axial loading after a ligamentous Lisfranc injury. With
      abduction stress, we were able to show a significantly greater difference between
      pre- and post-injury motion and the ability of both fixation methods to restrain
      motion to pre-injury levels. CLINICAL RELEVANCE: Abduction stress may be valuable
      when diagnosing and testing the transverse ligamentous Lisfranc injury. Both
      suture-button and screw fixation methods restrain motion at the Lisfranc complex.

PMID- 21733448
TI  - Biomechanical evaluation of a locking and nonlocking reconstruction plate in an
      osteoporotic calcaneal fracture model.
AB  - BACKGROUND: This study evaluated the effects of locking vs nonlocking
      configuration on the biomechanical performance of a calcaneal reconstruction
      plate in an osteoporotic cadaveric model. MATERIALS AND METHODS: A Saunders II B
      type calcaneal fracture was created in ten matched pair of cadaveric calcanei.
      Each pair was fixed with the Ascension calcaneal reconstruction plate using
      either locking or nonlocking screws in the same hole pattern. Specimens were
      axially loaded for 1000 cycles through the talus followed by load to failure.
      Statistical comparisons were made between the locking and nonlocking constructs
      on the displacements during cyclic loading as well as construct stiffness and
      load achieved at selected fragment displacements. RESULTS: No significant
      difference was detected between the locking and nonlocking constructs in
      displacement during cyclic loading (p > 0.2) for the numbers available. Similarly
      no significant difference was found in stiffness of the constructs between the
      groups: 445.7 +/- 148.8 (N/mm +/- SD) for the locking plate and 395.2 +/- 127.7
      for the nonlocking plate (p > 0.14). The load achieved at 2 mm displacement of
      the posterior fragment for the two groups were not different: locking plate at
      744.6 +/- 237.2 N and nonlocking plate at 739.3 +/- 269.7 N (p > 0.99).
      CONCLUSION: This study did not reveal a mechanical advantage to locking
      technology for calcaneal fractures with the selected plate and fracture model.
      CLINICAL RELEVANCE: While locking plate technology has shown mechanical
      advantages for fracture management in other osteoporotic models, in our fracture
      model and plating construct, this was not found. It is still unclear which
      fixation technique is most beneficial in these calcaneal fractures.

PMID- 21733449
TI  - Osteochondral autograft transplantation for acute osteochondral fractures
      associated with an ankle fracture.
AB  - BACKGROUND: Osteochondral fractures of the talar dome (OCFT) are frequently
      associated with ankle fractures. Controversy exists regarding the treatment of
      acute Grade III and IV OCFT. Osteochondral autograft transplantation (OAT) is a
      possible operative solution. MATERIALS AND METHODS: We performed OAT in 16
      patients with acute Grade III or IV OCFT. There were ten males and six females
      with the average age of 33.9 (range, 18 to 49) years. The average period of
      followup was 36.3 (range, 21 to 48) months. OCFT was identified, and clinically
      determined to be Grade III or IV using radiographs and intraoperative assessment.
      Seven patients were Grade III, nine patients were Grade IV OCFT. The OAT
      consisted of two sequential procedures: 1) harvesting of osteochondral autograft
      cylinder from the nonweightbearing surface of the ipsilateral knee, and 2)
      implanting the donor graft into the talar defect with press-fit technique. Single
      cylinder transplantation or a mosaicplasty was used. The outcome was determined
      by the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale,
      the simplified symptomatology evaluation, plain radiography and MRI. RESULTS: The
      mean size of the osteochonral fracture defects was 84.1 (range, 50 to 125) mm(2),
      and the mean depth was 2.5 (range, 1 to 5) mm. The mean AOFAS score was 95.4
      (range, 86 to 100) points postoperatively. At the latest followup, there was no
      radiographic evidence of post-traumatic arthritis. Based on the MRI of all
      patients, 93.7% of the osteochondral grafts showed bony integration and articular
      congruity of the talar dome. CONCLUSION: OAT was shown to be an effective
      treatment with excellent clinical outcome and imaging evidence of graft
      integration.

PMID- 21733450
TI  - Effect of a steel toe cap on forefoot injury pattern in a cadaveric model.
AB  - BACKGROUND: Crush injuries to the foot are a common workplace injury and a
      significant source of morbidity, disability and lost wages. Many regulatory
      bodies including the Occupational Safety and Health Administration (OSHA)
      recommend the use of safety shoes in certain occupations to help protect against
      these occupational hazards. However there remains controversy and paucity of
      published data regarding the protection afforded by a steel toe cap in regards to
      clinical injury pattern. This study looks to investigates the protective
      influence of a steel toe cap on crush injuries of the forefoot. MATERIALS AND
      METHODS: Five non-osteoporotic paired cadaver lower extremities were
      appropriately fitted to a standard work boot. One foot of each pair was fitted
      into a steel toe capped boot (designated ''ST'' group) while the other foot was
      fitted into an identical version of the work boot but without the protective
      steel toe cap (designated ''NST'' group). Each foot was crushed using a custom
      designed rig with a load of 150 lb dropped from a calibrated height of 3 feet to
      the forefoot. X-rays were obtained to assess fracture location & comminution and
      stress fluoroscopy was used to assess for any ligamentous Lisfranc injury.
      RESULTS: The NST group averaged 8.2 fractured bones per foot while the ST group
      averaged 3.6 fractured bones per foot (p = 0.001). The NST group demonstrated
      significantly more metatarsal fractures (3.2 fractures/foot) versus the ST group
      (one fracture/foot) (p = 0.020). The NST group demonstrated significantly more
      proximal phalanx fractures (4.2 fractures/foot) compared to the ST group (2.6
      fractures/foot) (p = 0.035). Middle and distal phalanx fractures were not
      significantly different between the two groups. A higher percentage of the bones
      fractured were deemed comminuted in the NST group (53.6%) versus the ST group
      (38.8%) although this did not reach statistical significance. CONCLUSION: This
      study demonstrated that the steel toe affords protective advantages in crush
      injuries to the foot in limiting the number and severity of metatarsal and
      proximal phalanx fractures. However the steel toe does not fully protect the
      forefoot from injury. CLINICAL RELEVANCE: Crush injuries to the foot are a common
      workplace injury. Strict adherence to workplace safety standards may limit the
      severity of crush injuries to the foot and additional safety measures such as
      metatarsal guards should be considered when appropriate.

PMID- 21733451
TI  - Valgus deformity of the great toe interphalangeal joint treated by reversed
      sliding osteotomy of the proximal phalanx: a case report.

PMID- 21733452
TI  - Technical tip: the crescentic shelf: a modified Ludoff osteotomy.

PMID- 21733453
TI  - Editorial: conflict of interest and FAI.

PMID- 21733454
TI  - J. Leonard Goldner Award 2010. Ligament balancing for total ankle arthroplasty:
      an in vitro evaluation of the elongation of the hind- and midfoot ligaments.
AB  - BACKGROUND: The changes in length of the hindfoot ligaments in response to
      alterations in ankle and subtalar joint orientation under physiologic load in
      eight fresh-frozen cadaver limbs were documented. RESULTS: In eversion, the
      tibiocalcaneal (11% +/- 4%, mean +/- SD], calcaneofibular (6% +/- 4%), posterior
      talofibular (7% +/- 4%), posterolateral talocalcaneal (21% +/- 9%), posteromedial
      talocalcaneal (33% +/- 45%) and calcaneonavicular (bifurcate) (8% +/- 7%)
      ligaments were elongated relative to their lengths in inversion. In inversion,
      the anterior capsular (talocalcaneal) (5% +/- 3%) and the plantar cuboidnavicular
      (5% +/- 6%) ligaments were elongated relative to their everted lengths. In
      dorsiflexion, the superficial (26% +/- 8%) and deep posterior tibiotalar (30% +/-
      13%), calcaneofibular (8% +/- 4%), tibiocalcaneal (4% +/- 2%) and lateral
      talocalcaneal (cervical) (2% +/- 1%) ligaments were elongated. In plantarflexion,
      the tibionavicular (26% +/- 5%) and the anterior talofibular (7% +/- 4%)
      ligaments were lengthened. No statistically significant elongation was documented
      in any ankle position for the anterior tibiotalar, talocalcaneal interosseous,
      plantar calcaneocuboid, calcaneocuboid (bifurcate), all components of the spring
      ligament, and the dorsal cuboidnavicular ligaments. CONCLUSION: Components of the
      deltoid ligament complex elongated largest at the ankle joint with any hindfoot
      movement but inversion. Therefore, selective release of components of the deltoid
      ligament complex may provide a means for achieving optimal ligament balancing in
      total ankle arthroplasty. Specifically, release of the superficial and deep
      posterior tibiotalar ligament may improve range of motion in total ankle
      arthroplasties, whereas the release of the tibiocalcaneal ligament may correct a
      varus talar tilt.

PMID- 21733455
TI  - STARTM ankle: long-term results.
AB  - BACKGROUND: There has been a resurgence of interest in total ankle replacement
      (TAR) due to improved results with newer prostheses. However, long-term
      survivorship data has been limited. The STARTM Ankle prosthesis is the first
      three-part prosthesis approved for use in the United States. MATERIALS AND
      METHODS: Eighty-four total ankle replacements were performed in 80 patients using
      the STARTM Ankle prosthesis and followed prospectively. Postoperatively, patients
      were evaluated with the AOFAS score for pain and function, and serial radiographs
      were evaluated for stability and alignment of the prosthesis. Implant failure,
      secondary procedures, and complications were recorded. RESULTS: Ninety-one
      percent of prostheses remain implanted at an average followup of 9.1 years. The
      probability of implant survival was 96% at 5 years and 90% at 10 years. An
      average 39-point improvement in the AOFAS ankle-hindfoot score was noted, from a
      mean of 43 to a mean of 82 points. We noted a statistically significant increase
      in both average pain and function sub-scores. Postoperative range of motion
      averaged 4.5 degrees of dorsiflexion and 35 degrees of plantarflexion. Ninety-two
      percent of the patients were satisfied with their outcome. Ten patients (13%)
      developed concerning osteolytic lesions. Change in prosthetic alignment and
      adjacent joint arthritis were similar to previous reports. We report 21
      complications, which included 14 additional surgical procedures. CONCLUSION: The
      first U.S. prospective long-term survivorship data with the STARTM Ankle
      prosthesis found it to be an excellent long-term option for the treatment of
      ankle arthritis.

PMID- 21733456
TI  - Minifragment plate fixation of high-energy navicular body fractures.
AB  - BACKGROUND: The purpose of this study was to assess the ability of miniplate
      fixation in navicular fractures to restore medial column stability, maintain
      reduction, and determine the impact this approach may have on the development of
      avascular collapse of the navicular. We hypothesized that comminuted fractures of
      the navicular can be safely reduced and maintained to union with minifragment
      plate fixation with a low incidence of avascular collapse. MATERIALS AND METHODS:
      A retrospective chart review was performed on 24 patients with navicular
      fractures treated with open reduction and internal fixation with minifragment
      plate fixation at a level one trauma center over a period of 6 years. RESULTS:
      All fractures united. No patient developed a deep infection. There was no loss of
      reduction. Isolated broken screws were evident in three patients (12.5%), with no
      plate breakage, and no implant failure by pullout. Four patients (17%) underwent
      plate removal for painful prominent hardware following fracture healing. Four
      patients (17%) developed radiographic arthrosis of the talonavicular joint. One
      patient (4%) had radiographic avascular collapse evident at 6 months and was
      treated with plate removal and an orthotic device. CONCLUSION: Minifragment
      fixation was a good alternative to independent lag screws for rigid stabilization
      of navicular body fractures.

PMID- 21733457
TI  - Salvage of failed total ankle arthroplasty with fusion using structural allograft
      and internal fixation.
AB  - BACKGROUND: The current study presents our experience with conversion of failed
      TAA to fusion. MATERIALS AND METHODS: A retrospective review of all failed total
      ankles converted to fusion from 1999 to 2009 was performed at our institution.
      RESULTS: Twelve total ankles were converted to isolated ankle fusions (Group I)
      and 12 converted to ankle-hindfoot fusions (Group II). All isolated ankle fusions
      were stabilized with anterior plate and screws with one nonunion. Structural bone
      graft was used in ten of 12. Mean outcome scores using the AOFAS-Ankle/Hindfoot
      score and Maryland Foot Score improved from preoperative values of 43 +/- 13 and
      56.7 +/- 14 to 67 +/- 12 and 71.2 +/- 16 postoperatively, respectively (p <
      0.05). All Group II ankle-hindfoot fusion patients were fixed using either
      anterior plate and screws, intramedullary nail, or a combination nail:plate
      construct. All received structural allografts. Five patients developed nonunion
      including four subtalar nonunions Preoperative scores on the AOFAS-AHS and MFS
      were 48.8 +/- 14 and 58.3 +/- 14. Postoperative scores were 51.2 +/- 17 for the
      AOFAS and 64.5 +/- 14 for the MFS. These changes were not statistically
      significant. However, the difference in nonunions was significant, p < 0.05.
      CONCLUSION: Failed total ankles can be successfully converted to fusion using
      structural bone graft and internal fixation. The primary risk appears to be
      nonunion of the subtalar joint when ankle-hindfoot fusion is required. We believe
      this risk can be decreased by using a separate approach for preparation of the
      subtalar joint.

PMID- 21733458
TI  - Radiographic evaluation of minimally invasive distal metatarsal osteotomy for
      hallux valgus.
AB  - BACKGROUND: The use of minimally invasive surgical technique for hallux valgus is
      controversial. The purpose of this study was to retrospectively evaluate the
      radiographic results of a minimally invasive distal metatarsal osteotomy for
      correction of hallux valgus. MATERIALS AND METHODS: From September 2005 to March
      2008, a minimally invasive distal metatarsal osteotomy was performed in 82
      patients (125 feet) for hallux valgus. The average age was 40.8 (range, 13 to 71)
      years. The mean followup period was 18.3 (range, 9 to 38) months. These patients
      were categorized into groups based on their gender, age, preoperative hallux
      valgus angle, and preoperative 1-2 intermetatarsal angle. The radiographs were
      reviewed for preoperative and final followup hallux valgus angle, 1-2
      intermetatarsal angle, and malunion or nonunion. A final followup hallux valgus
      angle greater than 20 degrees was defined as ''recurrence of deformity'' and
      represented a poor radiographic result. RESULTS: There were no nonunions but one
      case of plantarflexion malunion. One case had skin irritation due to prominent
      bone. A poor radiographic result occurred in 29 feet (23.2%). Of those 36 feet
      whose preoperative hallux valgus angle was equal or greater than 30 degrees, 23
      feet had a poor radiographic result (63.9%). Of those 89 feet whose preoperative
      hallux valgus angle was less than 30 degrees, only six feet had a poor
      radiographic result (6.7%) (p = 0.0001). The preoperative 1-2 intermetatarsal
      angle was found to have no statistically significant influence on poor
      radiographic results (p = 0.0539). Both the age and sex of the patients had no
      statistically significant influence (p = 0.8048 and 0.8604, respectively).
      CONCLUSION: Based on our results, we do not recommend use of this technique to
      treat moderate to severe hallux valgus (hallux valgus angle, 30) degrees. We
      believe a traditional open osteotomy with formal capsulorrhaphy would be a better
      choice of treatment.

PMID- 21733459
TI  - Transient bone marrow edema of the foot and ankle and its association with
      reduced systemic bone mineral density.
AB  - BACKGROUND: Transient bone marrow edema in the foot and ankle is an uncommon
      condition that should be distinguished from early avascular necrosis, stress
      fracture, or bone bruise. The diagnosis is based on the clinical presentation of
      pain with weightbearing without a history of trauma, combined with typical
      findings on magnetic resonance imaging. The etiology is not known, but recent
      case reports have suggested a possible link to systemic osteoporosis. This study
      examined the relationship between transient bone marrow edema of the foot and
      ankle and low systemic bone mineral density. MATERIAL AND METHODS: Over a period
      of 2 years, ten patients (eight women and two men) who were referred to our foot
      and ankle clinic were diagnosed as having transient bone marrow edema. Their mean
      age was 59 years. All underwent dual energy X-ray absorptiometry (DEXA) scan and
      were tested for serum vitamin D levels. The patients were treated with either a
      controlled ankle motion (CAM) walker or a stiff-soled postoperative shoe and all
      recovered in 5 to 10 months. RESULTS: Four patients were found to have
      osteoporosis and five had osteopenia. Only one patient had normal bone density.
      Serum vitamin D levels were low in nine patients, and normal in one. CONCLUSION:
      Our study found a strong association with transient bone marrow edema in the foot
      and ankle and low systemic bone mineral density, which appears to be due to a
      vitamin D deficiency. We recommend that, when TBME is diagnosed, patients should
      be referred for assessment and treatment of their bone mineral density.

PMID- 21733460
TI  - First metatarsal length change after basilar closing wedge osteotomy for hallux
      valgus.
AB  - BACKGROUND: Hallux valgus deformities with large intermetatarsal angles require a
      more proximal metatarsal procedure to adequately correct the deformity. Due to
      the relative ease of a closing wedge osteotomy, this technique was adopted but
      with concern over first metatarsal shortening. In this study, we primarily
      evaluated angular correction and first metatarsal shortening. MATERIALS AND
      METHODS: We evaluated 70 feet in 57 patients (average age, 54 years) with 52
      female and five male. The average followup was 14 (range, 6 to 45) months. The
      charts were reviewed for the presence of metatarsalgia. Digital radiographic
      measurements were made for pre- and postoperative hallux valgus and
      intermetatarsal angles, dorsiflexion angle of the first metatarsal, and absolute
      and relative shortening of the first metatarsal. RESULTS: The average hallux
      valgus angle improved from 31 to 11 degrees (p < 0.0001) and intermetatarsal
      angle from 13.2 to 4.4 angles (p < 0.0001). The absolute shortening of the first
      metatarsal was 2.2 mm and relative shortening was 0.6 mm. There was 1.3 degrees
      of dorsiflexion on average. CONCLUSION: Excellent correction of the deformity
      with minimal dorsiflexion or new complaints of metatarsalgia was found with this
      technique. The new method of assessing the relative shortening found to be less
      than the absolute shortening, which we feel more accurately reflects the
      functional length of the first metatarsal.

PMID- 21733461
TI  - The fate of syndesmotic screws.
AB  - BACKGROUND: A standard protocol for the management of syndesmosis injuries has
      yet to be established. Debate persists regarding number of screws, screw
      diameter, number of cortices purchased, and the need for and timing of screw
      removal. The purpose of this study was to identify factors related to screw
      fixation that may lead to the ultimate failure of syndesmosis fixation defined as
      a loss of reduction of the syndesmosis, screw breakage, screw loosening, or
      widening of the medial clear space. MATERIALS AND METHODS: A retrospective
      assessment of 137 consecutive patients who underwent open reduction and internal
      fixation of the distal tibiofibular joint at a single institution from 2004 to
      2008 was performed. Clinical and radiographic data were recorded regarding
      problems with questionable clinical significance (number of syndesmotic screws,
      number of cortices, screw diameter, screw location, hardware failure) and loss of
      syndesmosis reduction. A series of Fisher's exact tests were used to evaluate
      outcomes. A p value of 0.05 defined as significant. RESULTS: The 3.5-mm diameter
      screws were statistically more likely to break than 4- or 4.5-mm screws, but
      there was no difference in frequency of loss of reduction of the syndesmosis as a
      function of screw diameter; however, a power study revealed an n value of 1656
      would be required to show a significant difference. CONCLUSION: Screw diameter
      may have an effect on screw breakage but clinical significance of hardware
      failure itself is unknown including whether or not it results in a loss of
      reduction or failure of syndesmotic fixation.

PMID- 21733462
TI  - Extremely proximal fractures of the fifth metatarsal in the developmental age.
AB  - BACKGROUND: Numerous studies document the high incidence of this type of fracture
      of the foot in childhood due to the presence of the growth plate of the apophysis
      of the fifth metatarsal. Our aim in this study was to evaluate the presence and
      morphology of the growth nucleus and correlate its presence with fractures of the
      apophysis of the fifth metatarsal. MATERIALS AND METHODS: Between 2001 and 2003,
      we reviewed the radiographs of 481 patients (558 feet) between 6 months and 16
      years that were diagnosed with a fracture. We evaluated for the presence and
      morphology of the growth nucleus of the base of the fifth metatarsal in the 7- to
      16-year age group because this is the time interval in which the nucleus becomes
      visible radiographically. RESULTS: We identified the nucleus of the base of the
      fifth metatarsal in 115 patients for a total of 132 feet. A fracture of the fifth
      metatarsal was found in 12.8%. A misdiagnosis had been made in 47%. Misdiagnosis
      was strictly related to the presence of the growth nucleus of the apophysis
      except two cases where an accessory bone was present. CONCLUSIONS: Our study
      demonstrated a much higher incidence of the presence of the growth nucleus than
      documented in previous reports and that its morphology varied widely in relation
      to the stage of maturity of the patient and the radiographic technique. Its
      presence led to a high rate of misdiagnosis of a fracture.

PMID- 21733463
TI  - Correction of rigid equinovarus deformity using a multiplanar external fixator.
AB  - BACKGROUND: The rigid equinovarus foot deformity is a challenging condition
      treated by the orthopaedic foot and ankle surgeon. Rapid surgical correction of
      the deformity may lead to skin and neurologic complications. Gradual correction
      of the deformity with a multiplanar external fixator may decrease these
      complications. The purpose of this study was to present the results of a group of
      patients with rigid equinovarus deformities corrected using a multiplanar
      external fixator. MATERIALS AND METHODS: We retrospectively reviewed the results
      of correction of a rigid equinovarus deformity using multiplanar external
      fixation in a small group of patients. All patients underwent open Achilles
      lengthening, posterior capsule release, tibialis posterior tendon lengthening,
      flexor digitorum longus and flexor hallux longus lengthening, followed by
      application of a multiplanar external fixator with gradual correction of the
      deformity over a period of several weeks. Preoperative and postoperative
      deformity and AOFAS ankle-hindfoot scores were assessed. RESULTS: A total of
      eight rigid equinovarus deformities in six patients were treated with a
      multiplanar external fixator. The average patient age at the time of surgery was
      37.2 (range, 17 to 59 +/- 15.0) years. Causes of the deformity included trauma in
      three patients, traumatic brain injury in two patients, and long-standing
      rheumatoid arthritis in one patient. The average preoperative AOFAS ankle
      hindfoot score was 28.3 (range, 12 to 38 +/- 7.7). The average postoperative
      AOFAS ankle-hindfoot score was 68.1 (range 38 to 86 +/- 15.5) at an average
      followup of 71.9 (30 to 120 +/- 36.2) weeks. All deformities were gradually
      corrected to a plantigrade foot using a multiplanar external fixator over an
      average time of 5 (range, 4 to 6 +/- 0.8) weeks. After correction of the
      deformity, the external fixator was left in place for a time period equal to or
      twice the length of time it took to achieve correction. The average duration of
      external fixation was 10.8 (range, 8 to 16 +/- 2.8) weeks. Seven of eight
      deformities maintained correction at final followup. There was one case of
      recurrence. CONCLUSION: Correction of a rigid equinovarus deformity using a
      multiplanar external fixator was a viable treatment option. It allowed for
      correction of the deformity in a controlled manner, helping to reduce the risk of
      neurovascular complications that may result from single stage surgical
      correction. The risk of wound complications still exists with the correction of
      such a complex deformity.

PMID- 21733464
TI  - Relationship of the Scarf valgus-inducing osteotomy of the calcaneus to the
      medial neurovascular structures.
AB  - BACKGROUND: The Scarf valgus inducing osteotomy of the calcaneus is an operative
      technique to correct varus deformity of the hindfoot. It is versatile with
      significant corrective power; however, the neurovascular structures are in close
      proximity on the medial side and thus may be harmed during the osteotomy.
      Moreover, because this type of osteotomy can cause a great lateral translation,
      traction of the medial neurovascular structures is possible. We performed an
      anatomic study to evaluate the medial soft tissues after a lateralizing Scarf
      type calcaneal osteotomy. MATERIALS AND METHODS: The osteotomies were carried out
      on ten fresh-frozen cadaver specimens. We performed the osteotomy and induced
      valgus. Then we performed a medial dissection to identify the important medial
      structures: the medial and lateral plantar nerve (MPN , LPN) and the posterior
      tibial artery (PTA). We noted their relation to the osteotomy and their
      integrity. RESULTS: In several cases, one or more of the structures were
      sectioned. In five cases, all the structures crossed the osteotomy, four of which
      even a transection of one or both of the plantar nerves occurred. Although the
      PTA crossed the osteotomy in eight specimens, there was no transection of this
      structure. CONCLUSION: Scarf osteotomy of the calcaneus is a highly corrective
      osteotomy. However, caution must be exercised when performing as the medial
      neurovascular structures cross the osteotomy lines and transection can occur.
      CLINICAL RELEVANCE: When performing the osteotomy one should keep in mind that
      vigorous sawing and large displacement can cause damage to the medial
      neurovascular structures.

PMID- 21733465
TI  - Augmented tendon Achilles repair using a tissue reinforcement scaffold: a
      biomechanical study.
AB  - BACKGROUND: Missed or chronic Achilles tendon ruptures may have muscle atrophy
      and tendon retraction resulting in a defect that must be augmented with
      endogenous or exogenous materials. The Artelon(r) Tissue Reinforcement (ATR)
      scaffold is a readily available synthetic degradable poly(urethane urea) material
      used to augment tendon repair. The objective of this study was to compare human
      cadaveric Achilles tendon repairs with and without ATR. MATERIALS AND METHODS:
      Eighteen fresh frozen human cadaver limbs were dissected and the tendon
      transected 2 cm proximal to the calcaneal insertion. The control group of nine
      specimens was repaired with sutures, while the experimental group was repaired
      with sutures and reinforced with a tubularized patch of ATR. Specimens were
      tested for ultimate load to failure in an Instron machine after preloading to 10
      N followed by cyclic loading for 20 cycles from 2 to 30 N. RESULTS: The ultimate
      load to failure in the control group was a mean of 248.1 N +/- 19.6 (202 to 293
      at 95% CI) versus 370.4 N +/- 25.2 (312 to 428 at 95% CI) in the ATR group. The
      ultimate load to failure was 370.4 +/- 25.2 N (312 to 428 at 95% CI) and 248.1 +/
      19.6 N (202 to 293 at 95% CI) in the experimental and control groups,
      respectively (p = 0.0015). Creep of the ATR augmented group was 2.0 +/- 0.5 mm,
      compared to 3.1 +/- 1.1 mm for the control group (p = 0.026). CONCLUSION: ATR
      provided a statistically significant improvement in load to failure when compared
      to control specimens in a cadaver model. CLINICAL RELEVANCE: This finding may
      allow for development of more aggressive rehabilitation techniques following
      chronic Achilles tendon repairs.

PMID- 21733466
TI  - Deep peroneal nerve injury following external fixation of the ankle: case report
      and anatomic study.
AB  - BACKGROUND: We present a case of deep peroneal nerve injury after application of
      external fixator and conducted a cadaveric study of the relationship of the deep
      peroneal nerve to the lateral tibial cortex. MATERIALS AND METHODS: A case of toe
      drop after application of the external fixator is reported. Twelve cadaveric
      lower legs were dissected to identify the course of the deep peroneal nerve. The
      tibia were divided into four Zones with equal length. The course of the nerve
      through each Zone of the tibia was studied Result: In Zone 1, the deep peroneal
      nerve went around the fibular neck and was found on the interosseous membrane at
      the distal portion of Zone 1. In Zone 2, the nerve still lay on the interosseous
      membrane in all specimens at the posterior edge of the lateral tibia. In Zone 3,
      the nerve moved away from the interosseous membrane and had direct contact with
      the tibia in nine specimens. In Zone 4, the nerve was on the anterior surface of
      the distal tibia. CONCLUSION: The deep peroneal nerve can be injured during the
      application of a unilateral frame ankle external fixator. The nerve is
      particularly at risk in Zone 2 and 3. CLINICAL RELEVANCE: The study provided an
      anatomic basis for the safe application of a unilateral external fixator of the
      tibia.

PMID- 21733467
TI  - Tendon transfer for anterior and posterior tibialis dysfunction following hip
      dislocation: case report.

PMID- 21733468
TI  - Talar neck fracture after tibiotalar arthrodesis: case report.

PMID- 21733469
TI  - Halving the knots in percutaneous tendo Achilles repair: technique tip.

PMID- 21733470
TI  - Fixation of maximal shift Scarf osteotomy with inside-out plating: technique tip.

PMID- 21733471
TI  - FootForum: H-caps and patient-centric healthcare.

PMID- 21733472
TI  - Understanding the burden of depression.
AB  - Major depressive disorder is a highly prevalent, chronic, and disabling disease
      affecting millions of individuals worldwide. The burden of major depressive
      disorder includes impaired role functioning, decreased quality of life, the
      development of medical conditions, and increased morbidity and mortality. The
      long-term, recurrent nature of depression and its frequent resistance to
      available therapies lead to increased utilization of health services, which
      represents a large financial burden in health care costs. Major depressive
      disorder is often undertreated; however, even when treatment is adequate,
      remission rates are low and partial response is common.

PMID- 21733473
TI  - Administering and evaluating the results of the adult ADHD Self-Report Scale
      (ASRS) in adolescents.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common condition that can be
      difficult to diagnose in adolescents, since symptoms may vary among patients,
      evolve over time, and mimic symptoms of other disorders. Various rating scales
      are helpful to the clinician when evaluating patients for ADHD and should be used
      as part of a thorough assessment. Clinicians should use both informant- and self
      report rating scales to gather as much information as possible, while being aware
      that informants are subject to rater error and adolescents typically underreport
      symptoms. Rating scales can establish a baseline measure of the patient's symptom
      type and frequency, provide a framework for assessing symptom impairment, and aid
      clinicians in monitoring treatment response. The Adult ADHD Self-Report Scale
      (ASRS-v1.1) Symptom Checklist is a reliable self-report rating scale for
      adolescents as well as adults.

PMID- 21733474
TI  - Highlights of the international consensus statement on major depressive disorder.
AB  - The International Consensus Group on Depression gathered to outline a universal
      treatment algorithm for depression with the purpose of merging the evidence base
      and standards of clinical practice from various countries, including the United
      States, Europe, the Middle East, China, and Japan. This brief summary includes
      the following recommendations made by the consensus group: periodically screen
      all patients for depression, use measurement-based tools and full psychiatric
      assessments to complete differential diagnoses, refer patients to psychiatric
      specialists when appropriate, establish a therapeutic alliance with patients and
      their families, begin treatment with an antidepressant for moderate or severe
      depression, treat patients to remission, and continually monitor patients'
      symptomatic improvement.

PMID- 21733475
TI  - First episode of self-harm in older age: a report from the 10-year prospective
      Manchester Self-Harm project.
AB  - OBJECTIVE: Self-harm is closely related to completed suicide, especially in older
      age. As empirical research of self-harm in older age is scarce, with no studies
      confined to first-ever episodes in older age, we examined the clinical
      characteristics and the risk of repetition in first-ever self-harm in older age.
      METHOD: The Manchester Self-Harm (MaSH) project, a prospective cohort study,
      gathered data from September 1, 1997, through August 31, 2007, for individuals
      presenting with self-harm at emergency departments of 3 large hospitals in North
      West England. The characteristics of older patients (aged >= 55 years) who
      presented with a first-ever episode of self-harm are described and compared to
      those of middle-aged patients (35-54 years) presenting with a first-ever episode
      of self-harm. Following each episode, the MaSH form, a standard assessment form
      developed for the MaSH project, was completed by a clinician. Potential risk
      factors for repetition were examined by Cox regression analyses. RESULTS: A total
      of 374 older patients and 1,937 middle-aged patients presented with a first-ever
      episode of self-harm. The circumstances at the time of self-harm suggested higher
      suicidal intent in older age. In comparison with middle-aged patients, the rate
      of repetition in older-aged patients was lower (15.4% versus 11.8%, respectively;
      hazard ratio for older age = 0.65; 95% CI, 0.45-0.93; P = .019), although
      repetition was more often fatal among the older group (3.3% versus 13.6%,
      respectively; P = .009). The most important predictor of repetition in older age,
      ie, physical health problems, had no predictive value in middle-aged patients,
      whereas psychiatric characteristics had little impact on the risk of repetition
      in old age. CONCLUSIONS: High suicidal intent and different predictors of
      repetition in first-ever self-harm in older age highlight the need for age
      specific interventions beyond the scope of psychiatric care alone.

PMID- 21733476
TI  - Concise Health Risk Tracking scale: a brief self-report and clinician rating of
      suicidal risk.
AB  - OBJECTIVE: Monitoring suicidality and risk following initiation of antidepressant
      treatment is an essential component of clinical care, but few brief, reliable
      ratings of suicidal ideation and behavior in adults are available. This report
      evaluates the psychometric properties of a brief self- and clinician-rated
      measure of factors related to the risk of suicide attempt or completion. METHOD:
      Adult outpatients with nonpsychotic major depressive disorder (MDD) (n = 240)
      were enrolled from July 2007 through February 2008 and treated in an 8-week, open
      label trial with the clinician's choice of a selective serotonin reuptake
      inhibitor at 6 primary care and 9 psychiatric clinical care settings in the
      National Institute of Mental Health-funded Depression Trials Network. Diagnosis
      of MDD was determined by the Psychiatric Diagnostic Screening Questionnaire and
      an MDD checklist based on DSM-IV-TR criteria. Suicidal ideation and behavior are
      1 of 9 symptoms of MDD (depressed mood, loss of interest, appetite or weight
      change, sleep disturbance, reduced concentration or indecisiveness, fatigue or
      decreased energy, psychomotor agitation or retardation, feelings of
      worthlessness, or excessive guilt). The newly developed Concise Health Risk
      Tracking (CHRT) scale was administered both as the CHRT Self-Report (CHRT-SR) and
      Clinician Rating (CHRT-C) scales. Psychometric evaluations were conducted on both
      scales. RESULTS: The internal consistency (Cronbach alpha) was .77 for the 7-item
      CHRT-C and .78 for the 7-item CHRT-SR with a consistent factor structure, and 3
      independent factors (current suicidal thoughts and plans, perceived lack of
      social support, and hopelessness) for both versions. CONCLUSIONS: The 7-item CHRT
      C and the 7-item CHRT-SR have excellent psychometric properties and can be used
      to monitor suicidal risk in clinical practice and research settings. Whether
      either scale will predict suicide attempts or completions in actual practice
      would require a very large prospective study sample. TRIAL REGISTRATION:
      Clinicaltrials.gov Identifier: NCT00532103.

PMID- 21733477
TI  - Concise Associated Symptoms Tracking scale: a brief self-report and clinician
      rating of symptoms associated with suicidality.
AB  - OBJECTIVE: US Food and Drug Administration (FDA) warnings recommend monitoring
      negative symptoms associated with the initiation of antidepressant medications as
      these symptoms may interfere with full recovery and pose safety concerns. There
      is currently no brief, reliable rating instrument for assessing treatment
      emergent, negative symptoms. We evaluated the psychometric properties of 2
      versions of the newly developed 17-item Concise Associated Symptom Tracking
      (CAST) scale, the CAST Clinician Rating (CAST-C) and CAST Self-Rated (CAST-SR),
      which are brief instruments designed to measure the 5 relevant associated symptom
      domains (irritability, anxiety, mania, insomnia, and panic). METHOD: The study
      enrolled 265 outpatients with major depressive disorder (MDD), from July 2007
      through February 2008, into an 8-week, open-label trial with a selective
      serotonin reuptake inhibitor. Diagnosis of MDD was determined by the Psychiatric
      Diagnostic Screening questionnaire and an MDD checklist based on DSM-IV-TR
      criteria. Suicidality (suicidal ideation with associated behaviors) is 1 of 9
      symptoms of MDD (depressed mood, loss of interest, appetite or weight change,
      sleep disturbance, reduced concentration or indecisiveness, fatigue or decreased
      energy, psychomotor agitation or retardation, feelings of worthlessness or
      excessive guilt). Psychometric evaluations were conducted on both versions of the
      CAST. RESULTS: Cronbach alpha was .80 (CAST-C) and .81 (CAST-SR). Factor analysis
      identified 5 factors for each scale: (1) irritability, (2) anxiety, (3) mania,
      (4) insomnia, and (5) panic. When the item that cross-loaded on 2 factors was
      eliminated, the 16-item solution had a better goodness of fit (CAST-C: 0.90 vs
      0.87; CAST-SR: 0.88 vs 0.84). Cronbach alpha for the 16-item versions was .77
      (CAST-C) and .78 (CAST-SR). The 5 associated CAST symptom domains correlated well
      with other standard measures of these domains. CONCLUSIONS: The 16-item CAST-C
      and CAST-SR demonstrated excellent psychometric properties. These are potentially
      useful measures for monitoring treatment-emergent negative symptoms associated
      with antidepressants, as recommended by the FDA. TRIAL REGISTRATION:
      Clinicaltrials.gov Identifier: NCT00532103.

PMID- 21733478
TI  - Alcohol use disorders in schizophrenia: a national cohort study of 12,653
      patients.
AB  - BACKGROUND: Comorbid alcohol use disorders (AUDs) in schizophrenia are associated
      with increased morbidity, more inpatient treatment, and violent offending. It is
      of clinical importance to identify those with schizophrenia who may go on to
      develop an alcohol use disorder; however, the risk factors are not well
      understood. The aim of this study was to identify risk factors for the
      development of an AUD in patients after they had been diagnosed with
      schizophrenia. METHOD: We conducted a retrospective case-control study of 12,653
      individuals diagnosed with ICD-defined schizophrenia in Sweden in 1973-2004,
      using data from national registers. We tested the associations between individual
      factors (marital status, immigrant status, and previous violent offending),
      sociodemographic factors (income and education), and parental risk factors (AUDs,
      psychosis, and violent offending) ICD-defined and AUD development using logistic
      regression modeling. RESULTS: Over a median follow-up of 17.3 years, 7.6% of
      patients had at least 1 hospital diagnosis of AUD. After adjustment for gender
      and age at diagnosis in a multivariate regression model, previous violent
      offending (OR = 2.1; 95% CI, 1.8-2.5), low education (OR = 1.3; 95% CI, 1.1-1.5),
      maternal AUD (OR = 1.9; 95% CI, 1.4-2.7), and paternal AUD (OR = 1.9; 95% CI, 1.5
      2.3) remained independently associated with increased risk of patient AUD.
      CONCLUSIONS: AUDs are a common sequela of schizophrenia. Risk factors that could
      be identified at the time of first presentation include low educational
      attainment, previous violent offending, and parental history of AUDs and may
      inform clinical treatment and follow-up of those most at risk.

PMID- 21733479
TI  - The epidemiology of the proposed DSM-5 hoarding disorder: exploration of the
      acquisition specifier, associated features, and distress.
AB  - OBJECTIVE: Compulsive hoarding, characterized by the acquisition of and failure
      to discard a large number of possessions, is increasingly recognized as a
      significant public health burden. Many facets of the phenomenology, including an
      understanding of the population prevalence and associated features, are not yet
      fully understood. There is growing evidence that hoarding may warrant its own
      diagnosis in DSM-5, and it is therefore imperative to investigate the proposed
      cardinal symptoms along with correlated features that may be diagnostically
      relevant. METHOD: The present investigation examined the point prevalence of
      hoarding disorder in a nationally representative sample from the German
      population (N = 2,512). The hoarding definition considered in this study was
      derived from the Hoarding Rating Scale (HRS) and informed by 3 of the proposed
      DSM-5 criteria. Several hypothesized core components of hoarding disorder were
      also assessed using questions from the HRS and the UCLA Hoarding Severity Scale,
      including types of acquisition, perfectionism, indecision, procrastination,
      distress, and impairment. Data were collected from May 16, 2009, to June 19,
      2009. RESULTS: Analyses revealed a current population estimate of 5.8%. Hoarding
      prevalence did not differ between men and women. Hoarders were significantly more
      likely to buy items, acquire free things, and steal items they did not need,
      compared to nonhoarders (P < .001). Perfectionism, indecision, and
      procrastination were all uniquely and significantly associated with hoarding
      status (P < .001). Relationships between the proposed core features and
      distress/impairment are also detailed. CONCLUSIONS: The current investigation
      identified the proposed hoarding disorder as a highly prevalent syndrome;
      however, it should be noted that we were not able to fully ascertain the DSM-5
      criteria and that the current estimate may be higher than the actual population
      rate. Future research on the diagnostic criteria and associated features will be
      necessary to help clarify etiologic underpinnings, treatment efforts, and
      diagnostic nosology.

PMID- 21733480
TI  - Homeopathic treatments in psychiatry: a systematic review of randomized placebo
      controlled studies.
AB  - OBJECTIVE: To systematically review placebo-controlled randomized trials of
      homeopathy for psychiatric conditions. DATA SOURCES: Eligible studies were
      identified using the following databases from database inception to April 2010:
      PubMed, CINAHL, PsycINFO, Hom-Inform, Cochrane CENTRAL, National Center for
      Complementary and Alternative Medicine grantee publications database, and
      ClinicalTrials.gov. Gray literature was also searched using Google, Google
      Scholar, the European Committee for Homeopathy, inquiries with homeopathic
      experts and manufacturers, and the bibliographic lists of included published
      studies and reviews. Search terms were as follows: (homeopath* or homoeopath*)
      and (placebo or sham) and (anxiety or panic or phobia or post-traumatic stress or
      PTSD or obsessive-compulsive disorder or fear or depress* or dysthym* or
      attention deficit hyperactivity or premenstrual syndrome or premenstrual disorder
      or premenstrual dysphoric disorder or traumatic brain injury or fibromyalgia or
      chronic fatigue syndrome or myalgic encephalitis or insomnia or sleep
      disturbance). Searches included only English-language literature that reported
      randomized controlled trials in humans. STUDY SELECTION: Trials were included if
      they met 7 criteria and were assessed for possible bias using the Scottish
      Intercollegiate Guidelines Network (SIGN) 50 guidelines. Overall assessments were
      made using the Grading of Recommendations Assessment, Development and Evaluation
      procedure. Identified studies were grouped into anxiety or stress, sleep or
      circadian rhythm complaints, premenstrual problems, attention
      deficit/hyperactivity disorder, mild traumatic brain injury, and functional
      somatic syndromes. RESULTS: Twenty-five eligible studies were identified from an
      initial pool of 1,431. Study quality according to SIGN 50 criteria varied, with 6
      assessed as good, 9 as fair, and 10 as poor. Outcome was unrelated to SIGN
      quality. Effect size could be calculated in 16 studies, and number needed to
      treat, in 10 studies. Efficacy was found for the functional somatic syndromes
      group (fibromyalgia and chronic fatigue syndrome), but not for anxiety or stress.
      For other disorders, homeopathy produced mixed effects. No placebo-controlled
      studies of depression were identified. Meaningful safety data were lacking in the
      reports, but the superficial findings suggested good tolerability of homeopathy.
      A funnel plot in 13 studies did not support publication bias (chi(2)(1) = 1.923,
      P = .166). CONCLUSIONS: The database on studies of homeopathy and placebo in
      psychiatry is very limited, but results do not preclude the possibility of some
      benefit.

PMID- 21733481
TI  - Controversial issues in child psychiatry.

PMID- 21733482
TI  - Rediscovering adverse anticholinergic effects.

PMID- 21733483
TI  - Cognitive inhibition in suicidal depressed elderly: a case-control pilot study.

PMID- 21733484
TI  - In bipolar disorder beyond 10 weeks of treatment, the term antidepressants is a
      misnomer.

PMID- 21733485
TI  - Metabolic syndrome in inpatients treated with clozapine.

PMID- 21733489
TI  - An international consensus study of neuroleptic malignant syndrome diagnostic
      criteria using the Delphi method.
AB  - OBJECTIVE: The lack of generally accepted diagnostic criteria for neuroleptic
      malignant syndrome (NMS) impedes research and clinical management of patients
      receiving antipsychotic medications. The purpose of this study was to develop NMS
      diagnostic criteria reflecting a broad consensus among clinical knowledge
      experts, represented by an international multispecialty physician panel.
      PARTICIPANTS: Eleven psychiatrists, 2 neurologists, 2 anesthesiologists, and 2
      emergency medicine specialists participated in a formal Delphi consensus
      procedure. EVIDENCE: A core bibliography consisting of 12 prominent, current
      reviews of the NMS literature was identified by an objective, comprehensive
      electronic search strategy. Each panel member was given a copy of these
      references and asked to examine them before commencing the survey process.
      CONSENSUS PROCESS: After reviewing the core bibliography, panel members were
      asked to list any clinical signs or symptoms or diagnostic studies that they
      believed, on the basis of their knowledge and clinical experience, were useful in
      making a diagnosis of NMS. In subsequent survey rounds, panel members assigned
      priority points to these items, and items that failed to receive a minimum
      priority score were eliminated from the next round. Information about individual
      panel member responses was fed back to the group anonymously in the form of the
      group median or mean and the number of members who had ranked or scored each
      survey item. The a priori consensus endpoint was defined operationally as a
      change of 10% or less in the mean priority score for any individual item, and an
      average absolute value change of 5% or less across all items, between consecutive
      rounds. The survey was conducted from January 2009 through September 2009.
      RESULTS: Consensus was reached on the fifth round regarding the following
      criteria: recent dopamine antagonist exposure, or dopamine agonist withdrawal;
      hyperthermia; rigidity; mental status alteration; creatine kinase elevation;
      sympathetic nervous system lability; tachycardia plus tachypnea; and a negative
      work-up for other causes. The panel also reached a consensus on the relative
      importance of these criteria and on the following critical values for
      quantitative criteria: hyperthermia, > 100.4 degrees F or > 38.0 degrees C on at
      least 2 occasions; creatine kinase elevation, at least 4 times the upper limit of
      normal; blood pressure elevation, >= 25% above baseline; blood pressure
      fluctuation, >= 20 mm Hg (diastolic) or >= 25 mm Hg (systolic) change within 24
      hours; tachycardia, >= 25% above baseline; and tachypnea, >= 50% above baseline.
      CONCLUSIONS: These diagnostic criteria significantly advance the field because
      they represent the consensus of an international multispecialty expert panel,
      include critical values, provide guidance regarding the relative importance of
      individual elements, and are less influenced by particular theoretical biases
      than most previously published criteria. They require validation before being
      applied in clinical settings.

PMID- 21733490
TI  - A randomized, double-blind, placebo-controlled study of the safety and
      tolerability of high-dose quetiapine in patients with persistent symptoms of
      schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: Quetiapine is often prescribed at higher than approved doses. We
      investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d.
      METHOD: A trial was carried out from October 2003-September 2005 in 19 referral
      centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were
      randomized on the basis of persistent symptoms of moderate severity (< 30%
      improvement in total Positive and Negative Syndrome Scale score after >= 4 weeks
      of quetiapine). The 8 week, double-blind study compared continuation of
      quetiapine 800 mg/d (n = 43) versus 1,200 mg/d (n = 88). The primary outcome
      measure was emergent or worsening parkinsonism (Simpson-Angus Scale). Secondary
      outcomes were adverse events, metabolic side effects, and symptom severity.
      RESULTS: Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and >
      800-mg/d groups, respectively. Emergent or deteriorating parkinsonism in the high
      dose group was 3.1% greater (95% CI, -7.8% to 14.0%; P = .76) than in the 800
      mg/d group, a value that was within the a priori limit of 16% defined as
      noninferiority. Both doses of quetiapine were safe and well tolerated. Weight
      gain was greater in the high-dose group (1.7 kg over 12 weeks; >= 7% body weight,
      n = 11 [12.5%]) versus the 800-mg/d group (1.1 kg over 12 weeks; >= 7% body
      weight, n = 4 [9.3%]). The mean adjusted difference in weight gain (1.3 kg) was
      greater in the high-dose group (95% CI, 0.0-2.5; P = .044). Symptom severity
      declined, with no significant difference between groups. CONCLUSIONS: The results
      did not demonstrate any advantage for use of quetiapine outside the approved dose
      range. TRIAL REGISTRATION: www.clinicaltrials.gov Identifier: NCT00328978.

PMID- 21733491
TI  - Measurement of constructs using self-report and behavioral lab tasks: is there
      overlap in nomothetic span and construct representation for impulsivity?
AB  - There has been little empirical evidence examining the overlap in nomothetic span
      for self-report measures and construct representation for behavioral lab tasks in
      most psychological constructs. Using the personality trait of impulsivity as an
      example, the authors completed a meta-analysis of 27 published research studies
      examining the relationship between these methods. In general, although there is a
      statistically significant relationship between multidimensional self-report and
      lab task impulsivity (r = 0.097), practically, the relationship is small.
      Examining relationships among unidimensional impulsivity self-report and lab task
      conceptualizations indicated very little overlap in self-report and behavioral
      lab task constructs. Significant relationships were found between lack of
      perseverance and prepotent response inhibition (r = 0.099); between lack of
      planning and prepotent response inhibition (r = 0.106), delay response (r =
      0.134), and distortions in elapsed time (r = 0.104); between negative urgency and
      prepotent response inhibition (r = 0.106); and between sensation seeking and
      delay response (r = 0.131). Researchers should take care to specify which
      particular unidimensional constructs are operationalized with not only
      impulsivity, but with all traits. If self-report and lab task conceptualizations
      measure disparate aspects of impulsivity, we, as a field, should not expect large
      conceptual overlap between these methods.

PMID- 21733492
TI  - The genetic impact of the Q551R interleukin-4 receptor alpha polymorphism for
      aggressive or chronic periodontitis and the occurrence of periodontopathic
      bacteria.
AB  - OBJECTIVE: The Q551R polymorphism of the gene encoded for the alpha chain of the
      interleukin-4 receptor (IL-4RA) could influence both IL-4 and IL-13 signalling.
      Since both cytokines could be important in the pathogenesis of periodontitis the
      aim of this study was to evaluate putative associations of the Q551R polymorphism
      to generalized aggressive or chronic periodontitis and five periodontopathogens.
      DESIGN: 154 patients with severe generalized periodontitis (chronic: n=68, mean
      age=48.7 +/- 9.4 years; aggressive: n=86, mean age=40.4 +/- 9.8 years) and
      controls without periodontitis (n=89, mean age=46.2 +/- 10.8 years) were
      included. The Q551R polymorphism was analysed by PCR-SSP CTS-Kit, Heidelberg,
      Germany. Subgingival bacteria were determined molecular biologically using micro
      Ident test (HainLifescience, Nehren, Germany). Distributions of single alleles
      and genotypes were calculated by Chi(2)-test with Yates correction or Fisher's
      exact test. Adjusted odds ratios were generated by logistic regression with
      respect to established cofactors for periodontitis. RESULTS: The mutant allele
      R551 (p(Y)=0.013) and the genotypes QR+RR (p(B)=0.024) occurred more frequently
      amongst patients with chronic periodontitis vs. controls. Carriers of the Q551R
      polymorphism had an increased adjusted odds ratio for chronic periodontitis
      (OR=3.2, 95%CI 1.5-6.5, p=0.002) and severe periodontitis (chronic+aggressive) in
      general (OR=2.0, 95%CI 1.1-3.6, p=0.003). Moreover, in the total study cohort the
      Q551R polymorphism was associated with the presence of Tannerella forsythia
      (90.3% vs. 78.0%, p(Y)=0.01). CONCLUSIONS: The Q551R IL-4RA polymorphism is a
      putative risk indicator for severe chronic periodontitis, but was not significant
      associated to AP.

PMID- 21733493
TI  - Synergic effects of estradiol and progesterone on regulation of the hypothalamic
      neuronal nitric oxide synthase expression in ovariectomized mice.
AB  - Nitric oxide (NO) is a gaseous neurotransmitter that plays an important role in
      the regulation of sexual behavior in rodents. NO is produced, within the central
      nervous system, by the enzyme neural NO synthase (nNOS) whose expression is
      influenced by gonadal hormones. In previous studies, we demonstrated that part of
      the nitrergic hypothalamic and limbic system is influenced, in physiological
      conditions, by the hormonal fluctuations during the estrous cycle, but we were
      unable to distinguish among the role played by progesterone (P) or estradiol
      (E(2)) in inducing these changes. In the present study, we investigated the
      effects of E(2) and P (alone or together) on the nitrergic system of
      gonadectomized female mice, following a timing of administration that emulates
      the different phases of estrous cycle. In parallel, we tested the influence of
      the two hormones on sexual behavior, confirming that P works in synergistic
      fashion with E(2) to facilitate female receptivity. The quantitative analysis of
      nNOS-ir system demonstrated a statistically significant variation in the number
      of positive cells only in those part of the limbic-hypothalamic nitrergic system
      that are affected in cycling females, i.e. the bed nucleus of the stria
      terminalis, the arcuate nucleus and the medial preoptic area, with the highest
      number of positive neurons observed in E(2)+P group. The variable effects of E(2)
      and P may depend on the different distribution of their receptors within the
      analyzed nuclei, but the relationships among variations of estrogen and
      progesterone levels and in vivo modulation of nNOS expression remain unknown and
      needed further investigations.

PMID- 21733494
TI  - Evolution of gait abnormalities in SOD1(G93A) transgenic mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized
      by the loss of upper and lower motoneurons. Clinically, it is manifested by
      weakness, muscle atrophy and progressive paralysis and ends up with patients'
      death 2-5 years after diagnosis. Although these symptoms lead in many cases to
      gait deficits in patients, an exhaustive locomotor profile of animal models
      mimicking the disease has not been assessed yet. In this work we evaluated the
      locomotor performance of the SOD1(G93A) mouse model of ALS using computerized
      treadmill gait analysis. SOD1(G93A) mice presented early (8 weeks of age) gait
      abnormalities, evidenced by an increase in the time of the propulsion phase of
      hindlimb stance. The alterations progressed during the disease until a complete
      disturbance of normal gait. This finding is meaningful to the field because the
      identification of a significant difference in a functional endpoint as early as 8
      weeks might be a step forward resolving the debate about treatment of mice prior
      to the symptomatic phase in efficacy studies. These results also point out that
      digitizing analysis of treadmill locomotion may be useful to evaluate whether new
      therapeutic approaches are improving functional outcome of the animals.

PMID- 21733495
TI  - EWTD, the Temple Report and other drivers towards a consultant-delivered service.

PMID- 21733497
TI  - Measuring category intuitiveness in unconstrained categorization tasks.
AB  - What makes a category seem natural or intuitive? In this paper, an unsupervised
      categorization task was employed to examine observer agreement concerning the
      categorization of nine different stimulus sets. The stimulus sets were designed
      to capture different intuitions about classification structure. The main
      empirical index of category intuitiveness was the frequency of the preferred
      classification, for different stimulus sets. With 169 participants, and a within
      participants design, with some stimulus sets the most frequent classification was
      produced over 50 times and with others not more than two or three times. The main
      empirical finding was that cluster tightness was more important in determining
      category intuitiveness, than cluster separation. The results were considered in
      relation to the following models of unsupervised categorization: DIVA, the
      rational model, the simplicity model, SUSTAIN, an Unsupervised version of the
      Generalized Context Model (UGCM), and a simple geometric model based on
      similarity. DIVA, the geometric approach, SUSTAIN, and the UGCM provided good,
      though not perfect, fits. Overall, the present work highlights several
      theoretical and practical issues regarding unsupervised categorization and
      reveals weaknesses in some of the corresponding formal models.

PMID- 21733498
TI  - [Can the decision for admission to the hospital in community-acquired pneumonia
      be improved?].

PMID- 21733499
TI  - [Severe hypomagnesemia related to omeprazole].

PMID- 21733500
TI  - [Fusobacterium arising from hepatic abscess and abscessed ovarian neoplasm].

PMID- 21733501
TI  - [Inappropriate drug prescription and adverse drug effects in elderly patients].
AB  - AIMS: Inappropriate drug prescription (IP) has been related to higher
      hospitalization rates and development of adverse drug effects (ADE). We have
      studied the inappropriate drug prescriptions given to elderly patients admitted
      to the hospital and the frequency and severity of the adverse events related with
      them. PATIENTS AND METHODS: A prospective study was conducted in a sample of 100
      patients over 65 years admitted in an Internal Medicine Department in whom at
      least one inappropriate drug prescription (Beers and STOPP (B-S) criteria
      [Screening Tool of Older Person's Prescriptions]) as outpatients or during the
      first 48 hours after the admission. The relationship of the adverse events with
      the inappropriate drug prescription was established using the Naranjo algorithm.
      RESULTS: A total of 97 patients, mean age 81 years (range 66-101) were included.
      The total amount of medicines prescribed during the hospital stay was 865,
      average of 9 (range 3-16). Thirty two percent was being treated with more than 10
      drugs. A total of 153 (17.7%) were B-S drugs. There were 26 ADEs, 18 related with
      B-S drugs. Digoxin and lorazepam were the IP drugs most frequently prescribed and
      those related with a larger number of ADE. Fifty six percent of the ADEs were
      considered severe. Institutionalized elderly patients were treated with more
      drugs, but not more B-S medicaments. CONCLUSIONS: The frequency of ADEs related
      to IP is very high in the elderly. It is necessary to implement strategies to
      identify, and use properly these drugs in elderly population.

PMID- 21733502
TI  - Reevaluating the role of dilation and curettage in the diagnosis of pregnancy of
      unknown location.
AB  - OBJECTIVE: To evaluate the clinical utility of dilation and curettage (D&C) in
      diagnosing ectopic pregnancy (EP). DESIGN: Retrospective cohort study. SETTING:
      University hospital. PATIENT(S): Clinically stable women (n = 321) who underwent
      a diagnostic D&C with no visible intrauterine pregnancy (IUP) on transvaginal
      ultrasound or those with an abnormal hCG trend. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): EP or IUP made by final pathologic review. RESULT(S):
      Overall, 73.2% of the patients were ultimately diagnosed with EP and 26.8% were
      found to have a nonviable IUP. Those with EPs had significantly lower initial
      hCGs than those with nonviable IUPs and were more likely to have had a history of
      an EP. On ultrasound, the overall impression, the presence of free fluid, and the
      endometrial echo complex correlated well with the final diagnoses but did not
      have 100% predictive value. CONCLUSION(S): D&C remains valuable to differentiate
      EP from nonviable IUP and to avoid misdiagnosis and unnecessary exposure to
      methotrexate. Low initial hCG values and ultrasound findings such as a thin
      endometrial echo complex and the presence of free fluid are associated with but
      are not diagnostic of an ectopic pregnancy.

PMID- 21733503
TI  - National study of factors influencing assisted reproductive technology outcomes
      with male factor infertility.
AB  - OBJECTIVE: To evaluate the outcomes of assisted reproductive technology (ART)
      cycles for male factor infertility, and method of sperm collection. DESIGN:
      Historic cohort study. SETTING: Clinic-based data. PATIENTS: Cycles from the
      Society for Assisted Reproductive Technology Clinic Outcomes Reporting System
      database for 2004 to 2008 were limited to three groups: non-intracytoplasmic
      sperm injection (ICSI) and ICSI cycles for tubal ligation only; non-ICSI and ICSI
      cycles for male factor infertility only; and all cycles (regardless of
      infertility diagnosis) using ICSI only. INTERVENTION(S) AND MAIN OUTCOME
      MEASURE(S): Multivariate logistic regression was used to model the adjusted odds
      ratio (AOR) of clinical intrauterine gestation (CIG) and live birth (LB) rates
      for tubal ligation versus male factor infertility only; ICSI versus non-ICSI for
      male factor infertility only; and ICSI outcomes based on method of sperm
      collection. RESULT(S): Models for male factor infertility only versus tubal
      ligation only ICSI cycles had lower CIG (AOR 0.92) but not LB (AOR 0.87). No
      difference was seen for non-ICSI cycles. Within male factor infertility only
      cycles, ICSI had a worse outcome than non-ICSI for CIG (AOR 0.93) but not for LB
      (AOR 0.94). For all ICSI cycles with no male factor infertility and ejaculated
      sperm as the reference group, models showed better rates of CIG with male factor
      infertility ejaculated sperm (AOR 1.07) and with male factor infertility
      aspirated sperm (AOR 1.09). The LB rate was higher with male factor infertility
      ejaculated sperm only (AOR 1.04). CONCLUSION(S): The ICSI and sperm source
      influence CIG and LB rates in male factor infertility cases.

PMID- 21733504
TI  - Single-port laparoscopic cornual resection for a spontaneous cornual ectopic
      pregnancy following ipsilateral salpingectomy.
AB  - OBJECTIVE: To describe the single-port laparoscopic management of a spontaneous
      cornual ectopic pregnancy following ipsilateral salpingectomy. DESIGN: Case
      report and technique description. SETTING: University hospital. PATIENT(S): A 28
      year-old woman with a spontaneous cornual pregnancy of 5 weeks' gestation
      following previous ipsilateral salpingectomy. INTERVENTION(S): Single-port
      laparoscopic cornual resection (surgeon, Y.-W.K.). MAIN OUTCOME MEASURE(S): Serum
      beta-hCG levels. RESULT(S): Complete resolution of cornual pregnancy.
      CONCLUSION(S): We performed a successful single-port laparoscopic cornual
      resection for a spontaneous cornual ectopic pregnancy following ipsilateral
      salpingectomy.

PMID- 21733505
TI  - Single-nucleotide polymorphisms in the lysyl oxidase-like protein 4 and
      complement component 3 genes are associated with increased risk for endometriosis
      and endometriosis-associated infertility.
AB  - This study was conducted to assess genetic associations with endometriosis in a
      Puerto Rican population. Statistically significant differences in the allelic
      frequencies and genotype distribution of genetic variants in lysyl oxidase-like
      protein 4 (LOXL4) and complement component 3 (C3) were documented in patients
      with endometriosis-associated infertility versus controls, and in patients with
      endometriosis versus controls, respectively. In women who have the risk genotype
      at both single-nucleotide polymorphisms, the estimated risk for endometriosis
      nearly doubled.

PMID- 21733506
TI  - Importance of timing of gestational exposure to methotrexate for its teratogenic
      effects when used in setting of misdiagnosis of ectopic pregnancy.
AB  - OBJECTIVE: To report a case of embryopathy due to misadministration of
      methotrexate in the setting of suspected ectopic pregnancy that resulted in a
      different pattern of malformations than is typically seen with methotrexate.
      DESIGN: Case report. SETTING: Community hospital. PATIENT(S): A 30-year-old
      primigravida women exposed to methotrexate (50 mg/m(2)) at 5 6/7 weeks'
      gestation. INTERVENTION(S): The patient underwent amniocentesis because of
      abnormal results at the first-trimester genetic screening (low levels of
      pregnancy associated plasma protein A and hCG) and fetal echocardiogram because
      of single umbilical artery. MAIN OUTCOME MEASURE(S): Fetal anomalies. RESULT(S):
      The fetus was found to have a single umbilical artery, tetralogy of Fallot, and a
      "horseshoe lung," despite administration of high doses of folic acid. The
      pregnancy ultimately ended with fetal demise at 30 weeks. CONCLUSION(S): As
      medical management of ectopic pregnancy becomes more common, practitioners should
      be cautious about the potential teratogenic effects in unrecognized intrauterine
      pregnancies and be able to diagnose the myriad defects, including cardiac
      anomalies, that could result from such exposure.

PMID- 21733507
TI  - Prospective, observational study of the depth of anesthesia during oocyte
      retrieval using a total intravenous anesthetic technique and the Bispectral index
      monitor.
AB  - Fifty patients scheduled to undergo IVF received a standard anesthetic of
      fentanyl and propofol for induction, followed by propofol infusion, with
      Bispectral index values and modified Ramsey sedation scores recorded at 5-minute
      intervals for the duration of anesthesia care. Moderate sedation was found only
      transiently during the first 5-10 minutes of the oocyte retrieval, but thereafter
      the level of sedation increased, with deep sedation and general anesthesia
      measured in all patients as determined by both the Bispectral index scores and
      lack of response to painful stimulation.

PMID- 21733508
TI  - Effect of combined metformin and oral contraceptive therapy on metabolic factors
      and endothelial function in overweight and obese women with polycystic ovary
      syndrome.
AB  - In this randomized, double-blind, placebo-controlled study, 19 overweight women
      with polycystic ovary syndrome were randomized to a 3-month course of either
      metformin plus combined hormonal oral contraceptive (OC) (n = 9) or OC plus
      matched placebo (n = 10). After 3 months, both treatments had similar effects on
      androgen levels, lipid profile, insulin sensitivity, and serum inflammatory
      markers, but flow-mediated dilatation increased by 69.0% in the metformin plus OC
      group while it remained unchanged in the OC group. CLINICAL TRIAL REGISTRATION
      NO: NCT00682890.

PMID- 21733509
TI  - Single training session for first time pelvic C-clamp users: correct pin
      placement and frame assembly.
AB  - BACKGROUND: Unstable pelvic fractures with associated haemodynamic instability
      are major contributors of mortality and morbidity after blunt trauma. The pelvic
      C-clamp is one of the methods for emergency skeletal stabilization for pelvic
      ring injuries with posterior instability. The application of this device is
      taught on courses, but it is seldom used. The safety and efficiency of C-clamp
      application by trained first time users is unknown. We hypothesised that the
      pelvic C-clamp cannot be safely positioned on a training model after one training
      session. METHODS AND MATERIALS: A theoretical and a practical session on the
      application of the pelvic C-clamp was held within an interval of 11.2+/-4.4.
      Twenty-seven participants of various levels of training were assessed on accuracy
      and efficacy of the application of the pelvic C-clamp was applied to a pelvic
      model (Pelvic TrainerTM). RESULTS: 70.4% of all participants were able to place
      both pins inside the safe zone, whilst 81.5% of all pins were positioned safe.
      18.5% were considered to be in unsafe position. The distance to optimal target
      point was 9.6+/-7.8mm on the left (injured) hemipelvis and 8.7+/-7.8mm on the
      right (uninjured). The time needed for assembly was 99.7+/-39.7s, for placement
      it averaged at 133.9+/-74s. CONCLUSIONS: The majority of pins were placed into
      the safe zone on a training model within 4 min after one training session. 18.5%
      dangerous pin placement within 11 days of the training requires careful
      consideration (risk/benefit) in the context of a critically injured dying
      patient.

PMID- 21733511
TI  - Re: The invisible nail: a technique report of treatment of a pathological humerus
      fracture with a radiolucent intramedullary nail [Injury 2011;42:424-6].

PMID- 21733510
TI  - Evaluation of intrapleural contrast-enhanced abdominal pelvic CT-scan in
      detecting diaphragm injury in stable patients with thoraco-abdominal stab wound:
      a preliminary study.
AB  - BACKGROUND: Many of the patients with thoraco-abdominal stab wound remain
      asymptomatic; in this regard, previous studies reported that 7-48% of
      asymptomatic patients had diaphragm injury (DI). Thoracoscopy or multidetector
      computed tomography (MDCT) scan is the best method to detect DI. We aimed to
      evaluate the role of CT scan with intrapleural contrast to rule out DI in stable
      thoraco-abdominal stab wounds. METHOD: In a prospective study, we evaluated all
      haemodynamically stable patients with thoraco-abdominal stab wound, from October
      2009 to 2010. Exclusion criteria included patients who needed emergency
      thoracotomy or laparotomy, those who were haemodynamically unstable and those
      with blunt trauma or gunshot injury. In the CT-scan department, 500 cc of diluted
      meglumine diatrozate was transfused into the pleural space via a chest tube and
      the CT scan was performed from the dome of the diaphragm to the pelvic cavity. In
      the second step, all patients were taken for thoracoscopy within 24h after
      admission. The CT-scan slide was considered positive if one of the following
      signs was found: (1) the diaphragm was obviously injured as seen in CT-scan
      slides and (2) contrast agent was seen in the peritoneal cavity. Sensitivity and
      specificity were calculated for CT scan and thoracoscopy. RESULTS: Four out of 40
      patients had DI according to thoracoscopy. CT scan with intrapleural contrast
      predicted diaphragmatic injury correctly in all four patients. Considering
      thoracoscopy as the gold-standard method, the CT scan had two false-positive
      cases. The sensitivity of the intrapleural-contrast CT scan was 100% and its
      specificity was 94.4%. CONCLUSION: Our study showed that CT scan with
      intrapleural contrast can be an acceptable approach to rule out DI and limit the
      use of thoracoscopy for final diagnosis and repair of DI in cases with suspicious
      or positive CT-scan results, especially in trauma centres with high load of
      trauma patients and little accessible equipment.

PMID- 21733512
TI  - Complex suicide: self-incineration and acetaminophen overdose.

PMID- 21733513
TI  - Predictors of mortality following severe pelvic ring fracture: results of a
      population-based study.
AB  - INTRODUCTION: Traumatic disruption of the pelvic ring is uncommon but is
      associated with a high risk of mortality. These injuries are predominantly due to
      high energy blunt trauma such as a fall from height, road or workplace trauma,
      and severe associated injuries are prevalent, increasing the complexity of
      managing this patient group. The aim of this population-based study was to
      investigate predictors of mortality following severe pelvic ring fractures
      managed in an inclusive, regionalised trauma system. METHODS: Cases aged>=15
      years from 1st July 2001 to 30th June 2008 were extracted from the population
      based statewide Victorian State Trauma Registry for analysis. Patient
      demographic, prehospital and admission characteristics were considered as
      potential predictors of mortality. Multivariate logistic regression was used to
      identify predictors of mortality with adjusted odds ratios (AOR) and 95%
      confidence intervals (CI) calculated. RESULTS: There were 348 cases over the 8
      year period. The mortality rate was 19%. Patients aged>=65 years were at higher
      odds of mortality (AOR 7.6, 95% CI: 2.8, 20.4) than patients aged 15-34 years.
      Patients hypotensive at the scene (AOR 5.5, 95% CI: 2.3, 13.2), and on arrival at
      the definitive hospital of care (AOR 3.7, 955 CI: 1.7, 8.0), were more likely to
      die than patients without hypotension. The presence of a severe chest injury was
      associated with an increased odds of mortality (AOR 2.8, 95% CI: 1.3, 6.1),
      whilst patients injured in intentional events were also more likely to die than
      patients involved in unintentional events (AOR 4.9, 95% CI: 1.6, 15.6). There was
      no association between the hospital of definitive management and mortality after
      adjustment for other variables, despite differences in the protocols for managing
      these patients at the major trauma services (Level 1 trauma centres).
      CONCLUSIONS: The findings highlight the importance of effective control of
      haemodynamic instability for reducing the risk of mortality. As most patients
      survive these injuries, further research should focus on long term morbidity and
      the impact of different treatment approaches.

PMID- 21733514
TI  - Plenary address to the combined National Trauma Research Institute and
      Australasian Trauma Society's Annual Scientific Meeting held in Melbourne,
      Australia on November 19, 2010.

PMID- 21733515
TI  - Re: Predictive factors for cutting-out in femoral intramedullary nailing [Injury
      2010:41(December (12));1312-16].

PMID- 21733516
TI  - Knee chondral injuries: clinical treatment strategies and experimental models.
AB  - Articular cartilage has a very limited capacity to repair and as such premature
      joint degeneration is often the end point of articular injuries. Patients with
      chondral injury have asymptomatic periods followed by others in which discomfort
      or pain is bearable. The repair of focal cartilage injuries requires a precise
      diagnosis, a completed knee evaluation to give the correct indication for surgery
      proportional to the damage and adapted to each patient. Many of the surgical
      techniques currently performed involve biotechnology. The future of cartilage
      repair should be based on an accurate diagnosis using new MRI techniques.
      Clinical studies would allow us to establish the correct indications and surgical
      techniques implanting biocompatible and biodegradable matrices with or without
      stem cells and growth factors. Arthroscopic techniques with the design of new
      instruments can facilitate repair of patella and tibial plateau lesions.

PMID- 21733517
TI  - Fine mapping of chromosome 3q22.3 identifies two haplotype blocks in ESYT3
      associated with coronary artery disease in female Han Chinese.
AB  - OBJECTIVE: Genome-wide association study recently identified the chromosome
      3q22.3 as a novel locus associated with coronary artery disease (CAD). This study
      was designed to identify the critical haplotype blocks within this region in Han
      Chinese populations. METHODS: We selected 1920 CAD patients and healthy
      participants from Han Chinese and genotyped 22 single nucleotide polymorphisms
      (SNPs) spanning 150 kilobases (kb) chromosomal region flanking rs9818870, a SNP
      associated with CAD at 3q22.3 in Caucasian. RESULTS: Seven SNPs were found to be
      strongly associated with CAD in females and clustered in two haplotype blocks of
      ESYT3 gene. This was validated in two geographically isolated case-control
      populations. The two blocks were 14 and 25kb long, respectively. In a combined
      haplotype analysis, the odds ratios (95% confidence interval, permuted P value)
      were 0.70 (0.58-0.83, 2*10(-5)) and 1.44 (1.20-1.72, 5*10(-5)) for haplotypes TTG
      and CCA in block 1 as well as 0.73 (0.61-0.87, 3*10(-4)) and 1.35 (1.13-1.62,
      0.0013) for haplotypes TCG and CTT in block 2, respectively. ESYT3 was expressed
      in human lymphocyte, vascular endothelial cell, and smooth muscle cell. The risk
      factors including gender, obesity, hypertension, diabetes, and hyperlipidemia
      exhibited strong effects on the genetic contribution to CAD. CONCLUSION: We
      identified two haplotype blocks of ESYT3 gene in 3q22.3 region that likely harbor
      functional variants, which cooperate with other risk factors and play a role in
      the pathogenesis of coronary artery disease in females.

PMID- 21733518
TI  - Serum level of pigment epithelium-derived factor is a marker of atherosclerosis
      in humans.
AB  - OBJECTIVE: Pigment epithelium-derived factor (PEDF) could play a protective role
      against atherosclerosis. However, there is no clinical study to examine the
      relationship between serum level of PEDF and atherosclerosis in humans.
      METHODS/RESULTS: The study involved 317 consecutive outpatients in Kurume
      University Hospital (220 male and 97 female) with a mean age of 62.1+/-9.1. We
      examined whether serum level of PEDF were independently associated with vascular
      inflammation evaluated by [(18)F]-fluorodeoxyglucose positron emission tomography
      (FDG-PET) and intima-media thickness (IMT) in carotid artery in humans. Carotid
      [(18)F]-FDG uptake, an index of vascular inflammation within the atherosclerotic
      plaques, was measured as standardized uptake value (SUV). Mean serum PEDF level,
      carotid SUV and IMT values were 13.5+/-1.1 MUg/mL, 1.34+/-0.19, and 0.71+/-0.15
      mm, respectively. In multiple stepwise regression analysis, estimated glomerular
      filtration rate (p<0.001), males (p<0.001), homeostasis model assessment of
      insulin resistance index (p<0.05), heart rate (p<0.05), triglycerides (p<0.05),
      carotid IMT (p<0.05), waist circumference (p<0.05) and carotid SUV (p<0.05) were
      independently correlated to PEDF level (R(2)=0.332). CONCLUSION: The present
      study reveals that serum level of PEDF is independently associated with vascular
      inflammation and IMT, thus suggesting that PEDF level is a novel biomarker that
      could reflect atherosclerosis in humans.

PMID- 21733519
TI  - The effects of initial conditions and takeoff technique on running jumps for
      height and distance.
AB  - This study used a subject-specific model with eight segments driven by joint
      torques for forward dynamics simulation to investigate the effects of initial
      conditions and takeoff technique on the performance of running jumps for height
      and distance. The torque activation profiles were varied in order to obtain
      matching simulations for two jumping performances (one for height and one for
      distance) by an elite male high jumper, resulting in a simulated peak height of
      1.98m and a simulated horizontal distance of 4.38m. The peak height
      reached/horizontal distance travelled by the mass centre for the same
      corresponding initial conditions were then maximised by varying the activation
      timings resulting in a peak height of 2.09m and a horizontal distance of 4.67m.
      In a further two optimizations the initial conditions were interchanged giving a
      peak height of 1.82m and a horizontal distance of 4.04m. The four optimised
      simulations show that even with similar approach speeds the initial conditions at
      touchdown have a substantial effect on the resulting performance. Whilst the
      takeoff phase is clearly important, unless the approach phase and the subsequent
      touchdown conditions are close to optimal then a jumper will be unable to
      compensate for touchdown condition shortcomings during the short takeoff phase to
      achieve a performance close to optimum.

PMID- 21733520
TI  - Development of a pressure-driven injection system for precisely time controlled
      attoliter sample injection into extended nanochannels.
AB  - The rapidly developing interest in nanofluidics, which is used to examine liquids
      on an order that ranges from an attoliter to a femtoliter, correlates with the
      recent interest in decreased sample amounts, such as in the field of single-cell
      analysis. For general nanofluidic analysis, the fact that a pressure-driven flow
      does not limit the choice of solvents (aqueous or organic) is an important
      aspect. In this paper, an automated injection system using a pressure-driven flow
      for several hundred nanometer-sized channels (extended nanochannels) is
      described. By automatically, and independently, switching four pressure lines
      using solenoid valves controlled by a sequencer with a time resolution of 10 ms,
      550 aL sample band in minimum was reproducibly injected under normal phase
      conditions. The reproducibility of the band injection was improved by one order
      when compared with the previous injection method, which enables determination of
      time zero for injection. These facts are essential for the further band analysis
      in nanochannels, where diffusion is dominant. This injection system using
      pressure-driven flow can be used with any kind of solvent, which should make it a
      significant tool for nanofluidic applications, such as immunoassay, DNA analysis,
      and chromatography.

PMID- 21733521
TI  - Constructing chiral caves and efficiently separating enantiomers of glutamic acid
      with novel surface-imprinting technique.
AB  - Dimethylaminoethyl methacrylate (DMAEMA) was first graft-polymerized onto the
      surfaces of micron-sized silica gel particles in the manner of "grafting from" in
      a solution polymerization system, obtaining the grafted particles PDMAEMA/SiO(2).
      Then, the molecular imprinting towards the grafted PDMAEMA was conducted with one
      enantiomer of glutamic acid (Glu), L-Glu, as template molecule and with 2,2'
      dichlorodiethylether (DCEE) as crosslinking agent by adopting the novel surface
      molecular imprinting technique established by our research group, and the single
      enantiomer (L-Glu) molecule-imprinted material MIP-PDMAEMA/SiO(2) was obtained.
      With another enantiomer of glutamic acid, D-Glu, as the contrast compound, the
      recognition property of MIP-PDMAEMA/SiO(2) for L-Glu was investigated in depth
      with both static and dynamic methods, and its ability to separate L-Glu and D-Glu
      in the racemic solution was examined. The experiment results show that the
      surface-imprinted material MIP-PDMAEMA/SiO(2) has fine recognition selectivity
      and binding affinity for l-Glu, whereas its ability to combine D-Glu is poor. The
      selectivity coefficient of MIP-PDMAEMA/SiO(2) for L-Glu with respect to D-Glu is
      equal to 3.30, displaying an excellent chiral separation result. It is obvious
      that in this study, the substance separation at the molecular configuration level
      has been realized successfully.

PMID- 21733522
TI  - Advanced development in analysis of phytochemicals from medicine and food dual
      purposes plants used in China.
AB  - The concept of "Let food be thy medicine and medicine be thy food" was widely
      accepted for thousand years. It is now well known that some foods and food
      components have beneficial physiological and psychological effects. In China, the
      Ministry of Health of the People's Republic of China announced 87 items of
      materials, including 81 plants, could be used as both medicine and food.
      Increasing consumer demand for safety and health benefits, it is of critical
      importance to have high-quality and comprehensive data on bioactive compounds
      (phytochemicals) in these materials. In this review, we summarized the advanced
      development (2006-2010) in analysis of phytochemicals from medicine and food dual
      purposes plants (MFDPP) used in China.

PMID- 21733523
TI  - Methacrylate monolithic stationary phases for gradient elution separations in
      microfluidic devices.
AB  - Methacrylate monolithic stationary phases were produced in fused-silica chips by
      UV initiation. Poly(butyl methacrylate-co-ethylene dimethacrylate) (BMA) and
      poly(lauryl methacrylate-co-ethylene dimethacrylate) (LMA) monoliths containing
      30, 35 and 40% monomers were evaluated for the separation of peptides under
      gradient conditions. The peak capacity was used as an objective tool for the
      evaluation of the separation performance. LMA monoliths of the highest density
      gave the highest peak capacities (~40) in gradients of 15 min and all LMA
      monoliths gave higher peak capacities than the BMA monoliths with the same
      percentage of monomers. Increasing the gradient duration to 30 min did not
      increase the peak capacity significantly. However, running fast (5 min) gradients
      provides moderate peak capacities (~20) in a short time. Due to the system dead
      volume of 1 MUL and the low bed volume of the chip, early eluting peptides
      migrated over a significant part of the column during the dwell time under
      isocratic conditions. It was shown that this could explain an increased band
      broadening on the monolithic stationary phase materials used. The effect is
      stronger with BMA monoliths, which partly explains the inferior performance of
      this material with respect to peak capacity. The configuration of the connections
      on the chip appeared to be critical when fast analyses were performed at
      pressures above 20 bar.

PMID- 21733524
TI  - Measurement of the eddy diffusion term in chromatographic columns. I. Application
      to the first generation of 4.6mm I.D. monolithic columns.
AB  - The corrected heights equivalent to a theoretical plate (HETP) of three 4.6mm
      I.D. monolithic Onyx-C(18) columns (Onyx, Phenomenex, Torrance, CA) of different
      lengths (2.5, 5, and 10 cm) are reported for retained (toluene, naphthalene) and
      non-retained (uracil, caffeine) small molecules. The moments of the peak profiles
      were measured according to the accurate numerical integration method. Correction
      for the extra-column contributions was systematically applied. The peak parking
      method was used in order to measure the bulk diffusion coefficients of the sample
      molecules, their longitudinal diffusion terms, and the eddy diffusion term of the
      three monolithic columns. The experimental results demonstrate that the maximum
      efficiency was 60,000 plates/m for retained compounds. The column length has a
      large impact on the plate height of non-retained species. These observations were
      unambiguously explained by a large trans-column eddy diffusion term in the van
      Deemter HETP equation. This large trans-rod eddy diffusion term is due to the
      combination of a large trans-rod velocity bias (?3%), a small radial dispersion
      coefficient in silica monolithic columns, and a poorly designed distribution and
      collection of the sample streamlets at the inlet and outlet of the monolithic
      rod. Improving the performance of large I.D. monolithic columns will require (1)
      a detailed knowledge of the actual flow distribution across and along these
      monolithic rod and (2) the design of appropriate inlet and outlet distributors
      designed to minimize the nefarious impact of the radial flow heterogeneity on
      band broadening.

PMID- 21733525
TI  - Monolith-based immobilized metal affinity chromatography increases production
      efficiency for plasmid DNA purification.
AB  - Immobilized metal affinity monolith column as a new class of chromatographic
      support is shown to be superior to conventional particle-based column as plasmid
      DNA (pDNA) purification platform. By harnessing the affinity of endotoxin to
      copper ions in the solution, a majority of endotoxin (90%) was removed from the
      alkaline cell lysate using CuCl(2)-induced precipitation. RNA and remaining
      endotoxin were subsequently removed to below detection limit with minimal loss of
      pDNA using either monolith or particle-based column. Monolith column has the
      additional advantage of feed concentration and flowrate-independent dynamic
      binding capacity for RNA molecules, enabling purification process to be conducted
      at high feed RNA concentration and flowrate. The use of monolith column gives
      three fold increased productivity of pDNA as compared to particle-based column,
      providing a more rapid and economical platform for pDNA purification.

PMID- 21733526
TI  - Amination of surfaces via self-assembly of dopamine.
AB  - Catechols can strongly bind to a variety of substrates so as to functionalize the
      target surfaces by forming self-assembled monolayer. However, catecholic amine
      might self-oxidize and polymerize at high pH since the amine is susceptible to
      nucleophilic addition reaction that results in polymerized oligomers on surfaces.
      Therefore, the availability of amines for further derivation reaction would be
      restricted to a large extent. Herein, by controlling pH values to avoid self
      oxidative polymerization, dopamine (DA) forms thin and surface-adherent
      monolayers onto a wide range of inorganic and organic materials, including mica,
      silica, and Au surface, allowing amination of the surfaces that resemble
      commercially used aminosilanization. The self-assembly process was traced by
      surface topography and elemental composition analysis using atomic force
      microscope (AFM), X-ray photoelectron spectroscopy (XPS), and electrochemical
      characterization (electrochemical impedance spectroscopy and cyclic voltammetry
      measurements). Then, the aminated surfaces were used for secondary derivation
      reactions to create a variety of ad-layers, including patterned streptavidin
      through specific binding interaction with biotin and ferrocene surface via
      amidation reaction. The surface and interface properties of the obtained surfaces
      were tested by electrochemical measurements.

PMID- 21733527
TI  - Syntheses of silsesquioxane (POSS)-based inorganic/organic hybrid and the
      application in reinforcement for an epoxy resin.
AB  - A new inorganic/organic hybrid material containing silsesquioxane was prepared by
      the reaction of caged octa (aminopropyl silsesquioxane) (POSS-NH(2)) with n-butyl
      glycidyl ether (nBGE) and 1,4-butanediol diglycidyl ether (BDGE). The copolymers
      of POSS, nBGE, and BDGE could be obtained with varied feed ratio of POSS-NH(2),
      nBGE, and BDGE in the preparation. The hybrid material was added into an epoxy
      resin (E51) for enhancing the toughening and thermal properties of the epoxy
      resin. The results showed that the toughening and the thermal properties of the
      cured epoxy resin were greatly improved by the addition of the hybrid. The
      enhancement was ascribed to nano-scale effect of the POSS structure and the
      formation of anchor structure in the cured network. The investigation of kinetics
      for the curing process of the hybrid-modified epoxy resin revealed that two kinds
      of curing reactions occurred in different temperature ranges. They were
      attributed to the reactions between amino groups of the curing agent with epoxy
      groups of E51 and with residue epoxy groups in the hybrid. The reacting
      activation energies were calculated based on Kissinger's and Flynn-Wall-Ozawa's
      methods, respectively.

PMID- 21733528
TI  - Prenatal exposure to cigarette smoke causes persistent changes in the oxidative
      balance and in DNA structural integrity in rats submitted to the animal model of
      schizophrenia.
AB  - Epidemiological studies have indicated that prenatal exposure to environmental
      insults can bring an increased risk of schizophrenia. The objective of our study
      was to determine biochemical parameters in rats exposed to cigarette smoke (CS)
      in the prenatal period, evaluated in adult offspring submitted to animal model of
      schizophrenia induced by acute subanaesthetic doses of ketamine (5 mg/kg, 15
      mg/kg and 25 mg/kg). Pregnant female Wistar rats were exposed to 12 commercially
      filtered cigarettes per day, daily for a period of 28 days. We evaluated the
      oxidative damage in lipid and protein in the rat brain, and DNA damage in the
      peripheral blood of male adult offspring rats. To determine oxidative damage in
      the lipids, we measured the formation of thiobarbituric acid reactive species
      (TBARS) and the oxidative damage to the proteins was assessed by the
      determination of carbonyl groups content. We also evaluated DNA damage using
      single-cell gel electrophoresis (comet assay). Our results showed that rats
      exposed to CS in the prenatal period presented a significant increase of the
      lipid peroxidation, protein oxidation and DNA damage in adult age. We can observe
      that the animals submitted at acute doses of ketamine also presented an increase
      of the lipid peroxidation and protein oxidation at different doses and
      structures. Finally, we suggest that exposure to CS during the prenatal period
      affects two essential cerebral processes during development: redox regulation and
      DNA integrity, evaluated in adult offspring. These effects can leads to several
      neurochemical changes similar to the pathophysiology of schizophrenia.

PMID- 21733529
TI  - Negative impact of borderline global cognitive scores on quality of life after
      subthalamic nucleus stimulation in Parkinson's disease.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly
      improves quality of life (QoL) in Parkinson's disease (PD). Dementia is
      considered as a contraindication for STN-DBS. However, no controlled study
      assessed the impact of STN-DBS on the QoL and motor outcome in PD patients with a
      borderline global cognitive impairment. We studied clinical baseline and
      progression parameters in a cohort of STN-DBS patients with a global cognitive
      score still in the non-demented range but scoring in the lowest quartile of the
      Mattis Dementia Rating Scale (MDRS), a measure of global cognitive functioning.
      Data from a German randomised controlled study comparing DBS (60 patients) with
      best medical treatment (BMT, 59 patients) were analysed. Changes in patients' QoL
      scores were assessed using the Parkinson's disease questionnaire (PDQ-39) at
      baseline and at the 6 months follow up. Patients were split into four groups
      according to their MDRS performance at baseline and these groups were compared in
      the context of motor outcome and QoL. Twelve out of sixty patients of the STN-DBS
      group scored in the lowest quartile of the MDRS (range between one hundred thirty
      and one hundred thirty seven points). An individual analysis revealed that 3 of
      12 patients showed a clinical relevant improvement in QoL whereas the group
      statistics did not reveal any significant improvement in QoL measures after STN
      DBS compared to the BMT group. Since this failure to improve in QoL cannot be
      explained by a failure to improve in motor functions, stimulation settings and
      psychiatric scales after STN-DBS, the failure to improve in QoL in patients with
      a borderline global cognitive score might be specifically related to lower
      cognitive functioning.

PMID- 21733531
TI  - Hypertriglyceridemic waist: a simple clinical phenotype associated with coronary
      artery disease in women.
AB  - The aim of the present study was to compare the ability of the
      hypertriglyceridemic waist phenotype and the National Cholesterol Education
      Program-Adult Treatment Panel III (NCEP-ATP III) clinical criteria to predict
      coronary artery disease (CAD) risk in a sample of women. We studied 254 women
      among whom the presence/absence of CAD was assessed by angiography. The
      hypertriglyceridemic waist phenotype was defined as having both a high waist
      circumference (>=85 cm) and increased fasting triglyceride levels (>=1.5 mmol/L),
      whereas the presence of at least 3 of the 5 NCEP-ATP III criteria was used as the
      "reference" screening approach to identify women with the features of the
      metabolic syndrome. Women with hypertriglyceridemic waist were characterized by
      higher adiposity indices as well as by a more disturbed fasting metabolic risk
      profile compared with women without this phenotype. Similar differences were
      observed when comparing the metabolic profile of women with vs without at least 3
      of the NCEP-ATP III clinical criteria. Moreover, differences in the Framingham
      risk score were essentially similar when women were considered at low or high
      risk by either hypertriglyceridemic waist or by NCEP-ATP III clinical criteria (P
      < .0001). Finally, both clinical phenotypes were predictive of CAD
      (hypertriglyceridemic waist: relative odds ratio, 2.1; 95% confidence interval,
      1.1-3.8; P = .02; NCEP-ATP III clinical criteria: relative odds ratio, 2.5; 95%
      confidence interval, 1.4-4.6; P < .003). These results suggest that
      hypertriglyceridemic waist is a simple screening tool to identify women with
      clustering metabolic abnormalities and at increased CAD risk.

PMID- 21733532
TI  - Use of the Internet for sex partnership in men who have sex with men before HIV
      infection.
AB  - Over half (58.4%) of 77 recently diagnosed Chinese HIV infected men having sex
      with men (MSM) had networked sex partners through Internet in the year prior to
      their infections. Internet using MSM were younger (29.6y vs 38.7y; t = -4.77, P <
      0.01), better educated, more likely to have a regular sex partner, and have
      undergone regular HIV testing (Chi square = 5.57, P < 0.05). These
      characteristics could be used for planning public health interventions.

PMID- 21733533
TI  - [Fundamental topics in the training of new diagnostic imaging specialists].

PMID- 21733534
TI  - [Malignant phyllodes tumor of the breast with liposarcomatous differentiation.
      Solution to case 40].

PMID- 21733535
TI  - [PHACES syndrome (Pascual Castroviejo type II): prenatal and postnatal magnetic
      resonance imaging].
AB  - The neurocutaneous syndrome known by the acronym PHACE consists of the
      association of a segmental facial hemangioma with, among other entities,
      posterior fossa anomalies, cerebrovascular anomalies, cardiac involvement/aortic
      coarctation, and eye abnormalities. When ventral developmental defects are also
      present, the syndrome is referred to as PHACES. We report the prenatal and
      postnatal MRI findings in a case of PHACES with involvement of the right
      posteroinferior cerebellar artery. This case is exceptional because, to our
      knowledge, it is the first to report the findings at both prenatal and postnatal
      MRI and because of the unique vascular anomaly that widens the spectrum of
      possible intracranial arterial anomalies in this syndrome. 

PMID- 21733536
TI  - [Complete unilateral dilation of the vas deferens as a cause of an inguinal
      mass].
AB  - The complete unilateral dilation of the vas deferens is an extremely rare
      radiologic finding. Most cystic structures adjacent to the prostate can be
      grouped into cysts and diverticula. The finding of an inguinal mass makes it
      necessary to rule out intestinal hernias and other entities. We present the case
      of a patient who developed an inguinal mass secondary to unilateral dilation of
      the vas deferens. 

PMID- 21733537
TI  - [Early magnetic resonance imaging detection of a cavernous angioma after cranial
      radiotherapy for an anaplastic ependymoma in a boy].
AB  - Radiotherapy forms part of most therapeutic, preventive, and conditioning
      regimens in pediatric oncology. Numerous late secondary effects of cranial
      radiation are well known. However, radiation-induced cavernous angiomas (RICA)
      have been reported only sporadically and even fewer cases of earlier presentation
      of RICA have been reported. In this brief report, we describe a RICA that
      appeared in a boy treated for a CNS tumor (an infratentorial anaplastic
      ependymoma) after a short latency period between the end of radiotherapy and the
      development of the RICA. We comment on the different variables proposed to
      explain the formation of these lesions, as well as on their imaging features,
      treatment, prognosis, and follow-up. 

PMID- 21733538
TI  - [Solution to case 35. Multiple gastrointestinal stromal tumors of the small bowel
      in association with neurofibromatosis type 1].

PMID- 21733539
TI  - [Imaging biomarkers, quantitative imaging, and bioengineering].
AB  - Imaging biomarkers define objective characteristics extracted from medical images
      that are related to normal biological processes, diseases, or the response to
      treatment. To develop an imaging biomarker, it is necessary to carry out a series
      of steps to validate its relation with the reality studied and to check its
      clinical and technical validity. This process includes defining tests for the
      concepts and mechanisms; obtaining standardized and optimized anatomic,
      functional, and molecular images; analyzing the data with computer models;
      displaying data appropriately; obtaining the appropriate statistic measures; and
      conducting tests on the principle, efficacy, and effectiveness. In this article,
      we aim to explain the steps that must be established to enable biomarkers to be
      correctly applied, from their theoretical conception to their clinical
      implementation. To this end, we use the evaluation of angiogenesis in articular
      cartilage as an example.

PMID- 21733540
TI  - [Solution to case 37. Cocaine-induced rhabdomyolysis].

PMID- 21733541
TI  - Adsorption of ciprofloxacin on surface-modified carbon materials.
AB  - The adsorption capacity of ciprofloxacin (CPX) was determined on three types of
      carbon-based materials: activated carbon (commercial sample), carbon nanotubes
      (commercial multi-walled carbon nanotubes) and carbon xerogel (prepared by the
      resorcinol/formaldehyde approach at pH 6.0). These materials were used as
      received/prepared and functionalised through oxidation with nitric acid. The
      oxidised materials were then heat treated under inert atmosphere (N2) at
      different temperatures (between 350 and 900 degrees C). The obtained samples were
      characterised by adsorption of N2 at -196  degrees C, determination of the point
      of zero charge and by temperature programmed desorption. High adsorption
      capacities ranging from approximately 60 to 300 mgCPxgC(-1) were obtained (for
      oxidised carbon xerogel, and oxidised thermally treated activated carbon Norit
      ROX 8.0, respectively). In general, it was found that the nitric acid treatment
      of samples has a detrimental effect in adsorption capacity, whereas thermal
      treatments, especially at 900  degrees C after oxidation, enhance adsorption
      performance. This is due to the positive effect of the surface basicity. The
      kinetic curves obtained were fitted using 1st or 2nd order models, and the
      Langmuir and Freundlich models were used to describe the equilibrium isotherms
      obtained. The 2nd order and the Langmuir models, respectively, were shown to
      present the best fittings.

PMID- 21733542
TI  - Fate of hazardous aromatic substances in membrane bioreactors.
AB  - In this work, the removal of hazardous aromatic compounds was investigated in two
      types of membrane bioreactors (MBRs), based on cross-flow and semi dead-end
      filtration systems. BTEX and PAH were efficiently eliminated from wastewater
      during treatment via a membrane bioreactor (90-99.9%) but non-biotic processes,
      i.e. volatilisation and sorption, contributed significantly. The semi dead-end
      MBR showed slightly better removal efficiencies than the cross-flow MBR. However,
      non-biotic processes were more significant in the first process and, finally,
      degradation rates were higher in the cross-flow MBR. Higher degradation rates
      were explained by a higher bio-availability of pollutants. Differences in shear
      stress imposed in cross-flow and semi dead-end filtration systems radically
      modify the sludge morphology. High shear stress (cross-flow filtration) generates
      dispersed bacteria and larger quantities of dissolved and colloidal matter.
      Sorption of hydrophobic compounds (PAHs) on suspended solid was less marked in
      disaggregated sludge. The results suggest new strategies for improving micro
      pollutant degradation in MBRs.

PMID- 21733543
TI  - Differential toxicity of silver and titanium dioxide nanoparticles on Drosophila
      melanogaster development, reproductive effort, and viability: size, coatings and
      antioxidants matter.
AB  - Silver and titanium dioxide nanoparticles are known to induce oxidative stress in
      vitro and in vivo. Here we test if they impact development, mating success, and
      survivorship in Drosophila melanogaster, and if so, if these effects are
      reversible by antioxidants. Ingestion of nanotitanium dioxide during the larval
      stage of the life cycle showed no effects on development or survivorship, up to
      doses of 200 MUg mL(-1). Conversely, ingestion of nanosilver had major dose,
      size, and coating-dependent effects on each of these aspects of life history.
      Each of these effects was partially or fully reversible by vitamin C. Larvae
      growing on nanosilver supplemented with vitamin C showed a greater than twofold
      increase in survivorship compared to flies reared on nanosilver alone, and a
      threefold increase in mating success. Vitamin C also rescued cuticular and
      pigmentation defects in nanosilver fed flies. Biochemical assays of superoxide
      dismutase and glutathione show these markers respond to nanotitanium dioxide and
      nanosilver induced oxidative stress, and this response is reduced by vitamin C.
      These results indicate that life history effects of nanosilver ingestion result
      from oxidative stress, and suggest antioxidants as a potential remediation for
      nanosilver toxicity. Conversely, the lack of nanotitanium dioxide life history
      toxicity shows that oxidative stress does not necessarily result in whole
      organism effects, and argues that nanoparticle toxicity needs to be examined at
      different levels of biological organization.

PMID- 21733544
TI  - Is it possible to remediate a BTEX contaminated chalky aquifer by in situ
      chemical oxidation?
AB  - An industrial coating site in activity located on a chalky plateau, contaminated
      by BTEX (mainly xylenes, no benzene), is currently remediated by in situ chemical
      oxidation (ISCO). We present the bench scale study that was conducted to select
      the most appropriate oxidant. Ozone and catalyzed hydrogen peroxide (Fenton's
      reaction) were discarded since they were incompatible with plant activity.
      Permanganate, activated percarbonate and activated persulfate were tested. Batch
      experiments were run with groundwater and groundwater-chalk slurries with these
      three oxidants. Total BTEX degradation in groundwater was reached with all the
      oxidants. The molar ratios [oxidant]:[Fe(2+)]:[BTEX] were 100:0:1 with
      permanganate, 100:100:1 with persulfate and 25:100:1 with percarbonate.
      Precipitation of either manganese dioxide or iron carbonate (siderite) occurred.
      The best results with chalk slurries were obtained with permanganate at the molar
      ratio 110:0:1 and activated persulfate at the molar ratio 110:110:1. To avoid
      precipitation, persulfate was also used without activation at the molar ratio
      140:1. Natural Oxidant Demand measured with both oxidants was lower than 5% of
      initial oxidant contents. Activated percarbonate was not appropriate because of
      radical scavenging by carbonated media. Permanganate and persulfate were both
      effective at oxidant concentrations of ca 1 g kg(-1) with permanganate and 1.8 g
      kg(-1) with persulfate and adapted to site conditions. Activation of persulfate
      was not mandatory. This bench scale study proved that ISCO remediation of a
      chalky aquifer contaminated by mainly xylenes was possible with permanganate and
      activated or unactivated persulfate.

PMID- 21733545
TI  - Studies on atmospheric degradation of diazinon in the EUPHORE simulation chamber.
AB  - The gas phase atmospheric degradation of diazinon has been investigated at the
      large outdoor European Photoreactor (EUPHORE) in Valencia, Spain. The rate
      constant for reaction of diazinon with OH radicals was measured using a
      conventional relative rate method with di-n-buthylether as reference compound
      being k = (3.5 +/- 1.2) * 10-11 cm3 molecule-1 s-1 at 302 +/- 10 K and
      atmospheric pressure. The available evidence indicates that tropospheric
      degradation of diazinon is mainly controlled by reaction with OH radicals, and
      that the tropospheric lifetime with respect to the OH reaction is estimated to be
      around 4h whereas its lifetime with respect to the photolysis is higher than 1d
      under our conditions. Significant aerosol formation was observed following the
      reaction of diazinon with OH radicals, and the main carbon-containing products
      detected in the particle phase were hydroxydiazinon, hydroxydiazoxon and 2
      isopropyl-6-methyl-pyrimidinyl-4-ol.

PMID- 21733546
TI  - Seasonal change of PCDDs/PCDFs/DL-PCBs in the water of Ayase River, Japan:
      pollution sources and their contributions to TEQ.
AB  - In Japan, Ayase River is one of the most polluted rivers by PCDDs, PCDFs and
      dioxin-like PCBs, which are referred to as dioxins in this paper. The water
      samples of the river were collected once per month for a year, and dioxins were
      analyzed to examine the dioxin sources and their contributions to toxic
      equivalent (TEQ). The WHO-2006 TEQs ranged from 0.26 to 7.0 pg-TEQL(-1) and the
      average was 2.7 pg-TEQL(-1); eight of 12 samples exceeded the environmental
      quality standard in Japan (1.0 pg-TEQL(-1)). The TEQ value was high during the
      irrigation period from May to August. The most part of the dioxins in the river
      water existed in suspended solids (SS) and it seemed that the river received
      water with highly-dioxin-contaminated SS in the irrigation period. The homologue
      profiles of the water samples suggested that the dioxins were influenced by
      pentachlorophenol (PCP) and chlornitrofen (CNP) formulations which were widely
      used as herbicides for the paddy fields in Japan. According to TEQ apportionment
      estimated by using indicative congeners, the TEQ was mainly contributed by PCP.
      Moreover, it was also shown that the TEQ contributions of PCP and CNP
      formulations increased along with the increase of the total TEQ and the TEQ
      contribution was dominated by these herbicides during the irrigation period.
      Therefore, it was concluded that the herbicides-originated dioxins run off from
      the paddy fields into the river during the irrigation period and increased the
      dioxins level in the river water. The result from the principal component
      analysis was consistent with these conclusions.

PMID- 21733547
TI  - Treatment of polychlorinated biphenyls in two surface soils using catalyzed H2O2
      propagations.
AB  - Two surface soils contaminated with polychlorinated biphenyls (PCBs) collected
      from Superfund sites in the New England region of the United States, Fletcher
      Paints and Merrimack Industrial Metals, were evaluated for field treatment at the
      bench level using catalyzed H(2)O(2) propagations (CHP-modified Fenton's
      reagent). The two soils were first evaluated for the potential for in situ
      treatment based on two criteria: (1) temperature (< 40  degrees C after CHP
      reagent addition), and (2) hydrogen peroxide longevity (> 24h). In situ CHP
      remediation was more applicable to the Fletcher soil, while the Merrimack soil
      was better suited to ex situ treatment based on temperature increases and
      hydrogen peroxide lifetimes. Using the highest hydrogen peroxide concentrations
      appropriate for in situ treatment in each soil, PCB destruction was 94 % in the
      Fletcher soil but only 48% in the Merrimack soil. However, 98% PCB destruction
      was achieved in the Merrimack soil using conditions more applicable to ex situ
      treatment (higher hydrogen peroxide concentrations with temperatures > 40 
      degrees C). Analysis of degradation products by gas chromatography/mass
      spectroscopy showed no detectable chlorinated degradation products, suggesting
      that the products of PCB oxidation were rapidly dechlorinated and degraded. The
      results of this research document that the two PCB-contaminated soils studied can
      be effectively treated using aggressive CHP conditions, and that such a detailed
      bench study provides important information before implementing field treatment.

PMID- 21733548
TI  - Polychlorinated dibenzo-p-dioxins, dibenzofurans, and dioxin-like polychlorinated
      biphenyls in rice straw smoke and their origins in Japan.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      and dioxin-like polychlorinated biphenyls (DL-PCBs) contained in the smoke
      generated from rice straw burning in post-harvest paddy fields in Japan were
      analyzed to determine their congener profiles. Both the apportionment of toxic
      equivalent (TEQ) by using indicative congeners and the comparison of the homolog
      profiles showed that the PCDDs/PCDFs/DL-PCBs present in the rice-straw smoke were
      greatly influenced by those present as impurities in pentachlorophenol (PCP) and
      chlornitrofen (CNP, 4-nitrophenyl-2,4,6-trichlorophenyl ether) formulations that
      had been widely used as herbicides in paddy fields in Japan. Further, in order to
      investigate the effects of paddy-field soil on the PCDDs/PCDFs/DL-PCBs present in
      rice-straw smoke, PCDD/PCDF/DL-PCB homolog profiles of rice straw, rice-straw
      smoke and paddy-field soil were compared. Rice-straw smoke was generated by
      burning rice straw on a stainless-steel tray in a laboratory. The results
      suggested that the herbicides-originated PCDDs/PCDFs/DL-PCBs and the atmospheric
      PCDDs/PCDFs/DL-PCBs contributed predominantly to the presence of PCDDs/PCDFs/DL
      PCBs in the rice-straw smoke while the contribution of PCDDs/PCDFs/DL-PCBs formed
      during rice straw burning was relatively minimal. The major sources of the
      PCDDs/PCDFs/DL-PCBs found in the rice-straw smoke were attributed primarily to
      the paddy-field soil adhered to the rice straw surface and secondarily to the air
      taken by the rice straw. The principal component analysis supported these
      conclusions. It is concluded that rice straw burning at paddy fields acts as a
      driving force in the transfer of PCDDs/PCDFs/DL-PCBs from paddy-field soil to the
      atmosphere.

PMID- 21733549
TI  - Acquired glomerular lesions in patients with Down syndrome.
AB  - The long-term survival of persons with Down syndrome has dramatically increased
      over the past 50 years. There are no studies addressing the spectrum of
      glomerular lesions in these patients. We reviewed the clinical-pathologic
      characteristics of 17 patients with Down syndrome who underwent renal biopsy. The
      cohort consisted of 12 whites and 5 African Americans with mean age of 29 years
      (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal
      presentations included renal insufficiency (15 patients, mean serum creatinine
      3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean
      24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross
      hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5
      patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative
      glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2),
      pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis
      (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141
      months) was available on 16 patients (94%). Two patients (1 with membranous
      glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had
      complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental
      glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious
      glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci
      immune crescentic glomerulonephritis, 2 with membranoproliferative
      glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental
      glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In
      summary, a wide spectrum of glomerular diseases can be seen in patients with Down
      syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the
      most common. Renal biopsy is necessary to determine the type of glomerular lesion
      and appropriate treatment.

PMID- 21733550
TI  - The hormone receptor, human epidermal growth factor receptor 2, and molecular
      subtype status of individual tumor foci in multifocal/multicentric invasive
      ductal carcinoma of breast.
AB  - Multifocal/multicentric breast cancers are common. However, investigations of
      biomarkers such as estrogen receptor, progesterone receptor, and human epidermal
      growth factor receptor 2 in individual tumor foci of such cancers are rare. This
      study was designed to evaluate the status of the hormone receptors, human
      epidermal growth factor receptor 2, and its molecular subtypes in individual foci
      of multifocal/multicentric invasive ductal carcinoma of the breast and to
      identify the factors associated with the different phenotypes of individual foci.
      We performed immunohistochemical analyses of the estrogen receptor, progesterone
      receptor, cytokeratin 5/6, epidermal growth factor receptor, and p53 and
      fluorescence in situ hybridization of human epidermal growth factor receptor 2 in
      individual foci of 65 cases of multifocal/multicentric invasive ductal carcinoma
      and the associated ductal carcinoma in situ components using tissue microarrays.
      The estrogen receptor status differed in 2 (3%) of the 65 invasive ductal
      carcinomas, progesterone receptor status in 7 (11%), human epidermal growth
      factor receptor 2 status in 4 (6%), and molecular subtypes in 5 (8%). The
      presence of different molecular subtypes in the invasive tumor foci was
      associated with differences in histologic features (P = .005), high histologic
      and nuclear grade (P = .012 and P = .021, respectively), p53 overexpression (P =
      .006), and mixed molecular subtypes in the ductal carcinoma in situ components (P
      = .011). Multifocal/multicentric invasive ductal carcinomas usually have a single
      phenotype in terms of hormone receptors, human epidermal growth factor receptor
      2, and molecular subtypes; and thus, immunohistochemical analyses of the index
      tumor may be sufficient in routine practice. However, if multifocal/multicentric
      invasive ductal carcinomas are of high grade, of different histologic features,
      or of heterogeneous ductal carcinoma in situ component, biomarkers of the various
      foci need to be evaluated separately.

PMID- 21733551
TI  - Senescence in intraductal papillary mucinous neoplasm of the pancreas.
AB  - Intraductal papillary mucinous neoplasm of the pancreas is attracting attention
      as a precursor lesion of the invasive ductal adenocarcinoma, whereas it has been
      reported that some intraductal papillary mucinous neoplasms do not display
      progression to malignancy and remain almost unchanged in size and morphology.
      Recent studies have reported that oncogene-induced senescence has been observed
      in neoplasms, especially in premalignant lesions, and that it can play an
      important role in preventing malignant progression. To clarify the presence of
      senescence in intraductal papillary mucinous neoplasms, we analyzed the
      expression of several markers of senescence. The intraductal papillary mucinous
      neoplasms evaluated in this study were classified into 4 groups according to the
      degree of dysplasia. Senescence-associated beta-galactosidase activity and
      senescence-associated heterochromatin foci formation were investigated in 33
      cases of intraductal papillary mucinous neoplasms and 6 normal controls.
      Immunohistochemical analysis of p16(INK4a) and p15(INK4b) was performed in 158
      cases of intraductal papillary mucinous neoplasms and 10 normal controls. In the
      normal controls, neither senescence-associated beta-galactosidase activity nor
      senescence-associated heterochromatin foci formation was observed. Most of the
      normal epithelia were negative for either p16(INK4a) or p15(INK4b). For all 4
      markers, the percentages of positive cases reached a peak in intraductal
      papillary mucinous neoplasm with low-grade dysplasia and showed significant
      decreasing trends in the transition from intraductal papillary mucinous neoplasm
      with low-grade dysplasia to intraductal papillary mucinous neoplasm with an
      associated invasive carcinoma. Our results indicate that senescence is induced in
      the early stage of intraductal papillary mucinous neoplasm and gradually
      attenuated according to the progression. It is suggested that senescence plays a
      role in preventing malignant progression of intraductal papillary mucinous
      neoplasm.

PMID- 21733552
TI  - Pleomorphic adenoma arising in an incidental midline isthmic thyroid nodule: a
      case report and review of the literature.
AB  - Ectopic salivary gland tissue is common in the head and neck, usually associated
      with lymph nodes in lateral areas. It is rarely noted in the thyroid gland. Here
      we report the first case of a pleomorphic adenoma presenting as a midline nodule
      in the isthmus of thyroid in a 66-year-old man. We propose the possibility of
      origin in ectopic salivary gland tissue that may have aberrantly migrated with
      the median anlage from the foramen cecum in the base of the tongue during
      embryogenesis.

PMID- 21733553
TI  - Small cell carcinoma of the kidney: a clinicopathologic study of 14 cases.
AB  - Small cell carcinoma of the kidney is distinctively rare. We searched pathology
      files in 2 institutions and found 14 cases of renal small cell carcinoma. The
      patients' mean age at diagnosis was 59 years (range, 22-75 years); 8 were women,
      and 6 were men. Patients usually presented with hematuria (n = 6) and abdominal
      pain (n = 5). The mean tumor size was 7.1 cm (range, 3.5-14.0 cm). The small cell
      carcinoma was pure in 9 cases and mixed with high-grade urothelial carcinoma in 5
      cases. None was associated with any type of renal cell carcinoma. Tumor necrosis
      was present in all cases, and lymphovascular invasion was identified in 6 cases.
      The tumor invaded the perinephric adipose tissue in 13 cases and was confined to
      the kidney in only 1 case. Lymph node metastases were identified in all patients
      who underwent lymph node dissection (5/5). On immunostains, the small cell
      carcinoma cells were positive for pancytokeratin (11/12), chromogranin (6/9), and
      synaptophysin (8/9). Follow-up data were available for 13 patients, and 11 died
      of small cell carcinoma at a mean of 15 months (range, 4-31 months) after
      diagnosis. Of the 2 surviving patients, 1 was alive at 5 months after diagnosis,
      and the other, whose disease was confined to the kidney, was alive with no
      evidence of disease at 137 months. In summary, renal small cell carcinoma is a
      highly aggressive disease that often presents at an advanced stage with
      widespread metastases. Patients usually have a poor clinical outcome despite
      multimodal therapy. The frequent coexistence of small cell carcinoma with
      urothelial carcinoma suggests that renal small cell carcinomas may evolve from a
      preexisting urothelial carcinoma.

PMID- 21733554
TI  - Interobserver agreement for Polyomavirus nephropathy grading in renal allografts
      using the working proposal from the 10th Banff Conference on Allograft Pathology.
AB  - A classification schema for grading Polyomavirus nephropathy was proposed at the
      2009 Banff allograft meeting. The schema included 3 stages of Polyomavirus
      nephropathy: early (stage A), florid (stage B), and late sclerosing (stage C).
      Grading categories for histologic viral load levels were also proposed. To
      examine the applicability and the interobserver agreement of the proposed
      Polyomavirus nephropathy grading schema, we evaluated 24 renal allograft biopsies
      with confirmed Polyomavirus nephropathy by histology and SV40. Four renal
      pathologists independently scored the Polyomavirus nephropathy stage (A, B, or
      C), without knowledge of the clinical history. Viral load was scored as a percent
      of tubules exhibiting viral replication, using either a 3-tier viral load score
      (1: <=1%; 2: >1%-10%; 3: >10%) or a 4-tier score (1: <=1%; 2: >1%-<=5%; 3: >5%
      15%; 4: >15%). The kappa score for the Polyomavirus nephropathy stage was 0.47
      (95% confidence interval, 0.35-0.60; P < .001). There was a substantial agreement
      using both the 3-tier and the 4-tier scoring for the viral load (Kendall
      concordance coefficients, 0.72 and 0.76, respectively; P < .001 for both). A
      better complete agreement was found using the 3-tier viral load score. In this
      first attempt to evaluate the interobserver reproducibility of the proposed
      Polyomavirus nephropathy classifying schema, we demonstrated moderate kappa
      agreement in assessing the Polyomavirus nephropathy stage and a substantial
      agreement in scoring the viral load level. The proposed grading schema can be
      applied in routine allograft biopsy practice for grading the Polyomavirus
      nephropathy stage and the viral load level.

PMID- 21733555
TI  - Hyperplastic polyp of the duodenum: a report of 9 cases with immunohistochemical
      and molecular findings.
AB  - Benign serrated polyps are commonly found in the colorectum but have rarely been
      described in other parts of the gastrointestinal tract. We report a series of 9
      serrated polyps arising in the duodenum with clinicopathologic features,
      immunohistochemical expression profile of mucins (MUC2, MUC5AC, MUC6), and
      molecular analysis for BRAF and KRAS. The polyps were diagnosed as incidental
      endoscopy findings in 9 different patients, comprising 3 male and 6 female
      patients, with a mean age of 52.2 years (range, 21-72 years). The second part of
      the duodenum was the most common site (n = 5), followed by the ampulla (n = 1)
      and the distal duodenum (n = 1), with the location of the 2 remaining polyps
      unspecified. Other upper gastrointestinal tract pathology features included
      Barrett esophagus for 5 patients, Helicobacter gastritis for 1 patient, and mild
      chronic gastritis for 1 patient. The histologic appearance of the polyps was
      similar to microvesicular hyperplastic polyp in the colorectum. Immunostaining
      for mucins showed MUC6 expression in the crypt bases of all polyps, MUC5AC
      expression in 8 cases (89%), and mucin 2 expression in 6 cases (67%). Molecular
      testing was successful in 6 polyps, showing BRAF mutation (V600E) in 2 polyps,
      KRAS mutation in 2 polyps, and no mutation for either gene in 2 polyps.
      Colonoscopy reports were available for 6 patients, of whom 4 were diagnosed with
      hyperplastic polyps or sessile serrated polyps in the colorectum. However, no
      patient met the criteria for serrated polyposis. Although probably rare and of
      uncertain malignant potential, hyperplastic polyp should be considered in the
      differential diagnosis of benign duodenal polyp.

PMID- 21733556
TI  - Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft
      parts.
AB  - Pleomorphic hyalinizing angiectatic tumor of soft parts is a recently recognized,
      low-grade mesenchymal neoplasm of uncertain lineage. It is characterized by
      clusters of ectatic, fibrin-lined, thin-walled vessels surrounded by pleomorphic
      but mitotically inert spindled cells with frequent intranuclear inclusions and a
      variable inflammatory component. Here, we report a case of recurrent pleomorphic
      hyalinizing angiectatic tumor in a 37-year-old white woman. Touch imprint
      cytologic analysis revealed oval and spindled cells with fine chromatin,
      occasional prominent intranuclear inclusions, and intracytoplasmic pigment. The
      histologic features of the cells constituting the bulk of tumor were those
      characteristic of a putative precursor lesion ("early pleomorphic hyalinizing
      angiectatic tumor") as well as another recently described entity known as
      hemosiderotic fibrohistiocytic lipomatous lesion. Cytogenetic analysis revealed 2
      unbalanced translocations involving chromosomes 1 and 3 and chromosomes 1 and 10,
      with a karyotype of 45,XX,der(1)t(1;3)(p31;q12),
      3,der(10)t(1;10)(p31;q25)[11]/46,XX[4], thus suggesting that this disease is
      neoplastic. The controversies in classification of these lesions are also
      discussed.

PMID- 21733557
TI  - In immunocompromised patients, Epstein-Barr virus lymphadenitis can mimic
      angioimmunoblastic T-cell lymphoma morphologically, immunophenotypically, and
      genetically: a case report and review of the literature.
AB  - The development of lymphomas and solid malignancies in association with
      immunosuppression is a well-documented occurrence in the medical literature. We
      report the case of a young man who developed progressive diffuse lymphadenopathy
      with associated extremely high levels of serum Epstein-Barr virus in the setting
      of chronic immunosuppressive treatment of glomerulonephritis. Excisional biopsy
      of a right inguinal node revealed a sclerosing process with the morphologic
      appearance of angioimmunoblastic T-cell lymphoma with a CD3(+), CD4(+)
      immunophenotype. In situ hybridization of Epstein-Barr virus-encoded RNA was
      positive. Molecular probe studies demonstrated a clonal T-cell population. Upon
      reduction of immunosuppression, the patient's lymphadenopathy and Epstein-Barr
      virus titer have resolved without recurrence over 2 years time. This case
      demonstrates that a benign Epstein-Barr virus-associated process can mimic
      angioimmunoblastic T-cell lymphoma and should be considered particularly in the
      setting of immunosuppression, emphasizing the need for close communication with
      the treating physician in the interpretation of lymph node biopsies.

PMID- 21733558
TI  - Cross-talk between chronic lymphocytic leukemia cells and bone marrow endothelial
      cells: role of signal transducer and activator of transcription 3.
AB  - Chronic lymphocytic leukemia bone marrow is characterized by increased
      angiogenesis. However, the molecular mediators of neovascularization and the
      biologic significance of increased endothelial cell proliferation in chronic
      lymphocytic leukemia require further investigation. Because signal transducer and
      activator of transcription 3 is constitutively activated in chronic lymphocytic
      leukemia, we studied the role of signal transducer and activator of transcription
      3 in modulating vascular endothelial growth factor expression and the effect of
      vascular endothelial cells on chronic lymphocytic leukemia cells. Using chromatin
      immunoprecipitation, we found that anti-signal transducer and activator of
      transcription 3 antibodies immunoprecipitated DNA of signal transducer and
      activator of transcription 3, vascular endothelial growth factor, and other
      signal transducer and activator of transcription 3-regulated genes. In addition,
      signal transducer and activator of transcription 3-short interfering RNA
      significantly reduced messenger RNA levels of vascular endothelial growth factor
      in chronic lymphocytic leukemia cells, suggesting that signal transducer and
      activator of transcription 3 induces vascular endothelial growth factor
      expression in chronic lymphocytic leukemia. Remarkably, bone marrow chronic
      lymphocytic leukemia cells expressed high levels of vascular endothelial growth
      factor, and high vascular endothelial growth factor levels were detected in the
      plasma of patients with untreated chronic lymphocytic leukemia and correlated
      with white blood cell count. Chronic lymphocytic leukemia bone marrow biopsies
      revealed increased microvascular density and attachment of chronic lymphocytic
      leukemia cells to endothelial cells. Coculture of chronic lymphocytic leukemia
      cells and human umbilical vein endothelial cells showed a similar attachment.
      Furthermore, coculture studies with human umbilical vein endothelial cells showed
      that human umbilical vein endothelial cells protected chronic lymphocytic
      leukemia cells from spontaneous apoptosis by direct cell-to-cell contact as
      assessed by flow cytometry using annexin V. Our data suggest that constitutively
      activated signal transducer and activator of transcription 3 induces vascular
      endothelial growth factor production by chronic lymphocytic leukemia cells and
      that chronic lymphocytic leukemia cells derive a survival advantage from
      endothelial cells via cell-to-cell contact.

PMID- 21733559
TI  - Renal medullary carcinomas: histopathologic phenotype associated with diverse
      genotypes.
AB  - Chromosomal abnormalities and gene mutations have become major determinants in
      the classification of kidney carcinomas. Most renal medullary carcinomas develop
      in patients with hereditary sickle cell disease, but sporadic cases unassociated
      with sickle cell disease have also been described, for which underlying genetic
      abnormality is unknown. We evaluated 3 patients with renal medullary carcinoma (1
      patient with sickle cell disease and 2 patients without sickle cell disease) for
      germ line and somatic mutations in genes commonly involved in pathogenesis of
      renal carcinomas using denaturing high-performance liquid chromatography and
      direct sequencing. Chromosomal abnormalities were studied by the conventional
      cytogenetic and SNP arrays analysis. Expression of hypoxia-inducible factor
      1alpha was examined using immunohistochemistry. Two new mutations in the gene for
      fumarate hydratase were identified in 1 case of medullary renal carcinoma without
      sickle cell disease: a germ line mutation in exon 6 (R233H) and an acquired
      (somatic) mutation in exon 8 (P374S). No fumarate hydratase mutations were
      identified in the other 2 patients. The second sporadic case of renal medullary
      carcinoma harbored double somatic mutations in von Hippel-Lindau gene, and renal
      medullary carcinoma in the patient with sickle cell disease showed von Hippel
      Lindau gene promoter methylation (epigenetic silencing). No consistent pattern of
      chromosomal abnormalities was found between 2 cases tested. All 3 cases showed
      increased hypoxia-inducible factor 1alpha expression. Medullary renal carcinomas
      from patients with or without sickle cell disease show involvement of genes
      important in hypoxia-induced signaling pathways. Generalized cellular hypoxia (in
      sickle cell disease) or pseudohypoxia (in tumors with fumarate hydratase and von
      Hippel-Lindau mutations or epigenetic silencing) may act alone or in concert at
      the level of medullary tubular epithelium to promote development of this rare
      type of renal carcinoma, which could then be genetically reclassified as either
      fumarate hydratase-associated renal carcinomas or high-grade clear cell renal
      cell carcinomas.

PMID- 21733560
TI  - In situ follicular lymphoma with progressive transformation of the germinal
      centers confirmed by laser capture microdissection, IGH gene rearrangement
      analysis, and fluorescence in situ hybridization for t(14;18).
AB  - The authors report an unusual case of in situ follicular lymphoma associated with
      progressive transformation of the germinal centers. The patient was a 74-year-old
      Chinese woman with sequential lymphadenopathy in the right and left cervical
      regions over a period of 2 months. The first biopsy revealed in situ follicular
      lymphoma with progressive transformation of germinal centers, and the biopsy of
      the second lymph node led to a diagnosis of in situ follicular lymphoma. The
      immunophenotype, polymerase chain reaction amplification of the immunoglobulin
      heavy chain gene, and fluorescence in situ hybridization for t(14;18) were
      analyzed in each biopsy specimen, which showed both specimens to have
      t(14;18)(q32;q21) and revealed progression from polyclonality to monoclonality.
      These findings suggest a case of multicentric in situ follicular lymphoma and
      provide new insights into the pathogenesis of this disease.

PMID- 21733561
TI  - Frameshift mutations of vacuolar protein sorting genes in gastric and colorectal
      cancers with microsatellite instability.
AB  - Vacuolar protein sorting plays crucial roles in the traffic of molecules between
      cellular organelles. Although involvement of vacuolar protein sorting proteins in
      cancer is known, genetic alterations of VPS genes have not been reported in
      cancers. We found that VPS4B, VPS13A, VPS13B, VPS13C, VPS33A, VPS35, VPS37B,
      VPS37D, VPS41, and VPS54 have mononucleotide repeats in their coding sequences.
      To see whether these genes are mutated in cancers with microsatellite
      instability, we analyzed the mononucleotide repeats in 30 gastric cancers with
      high microsatellite instability, 13 gastric cancers with low microsatellite
      instability, and 45 gastric cancers with stable microsatellites and 40 colorectal
      cancers with high microsatellite instability, 14 colorectal cancers with low
      microsatellite instability, and 45 colorectal cancers with stable microsatellites
      by single-strand conformation polymorphism. We found mutations of VPS13A, VPS13B,
      VPS13C, VPS33A, VPS35, VPS37B, VPS41, and VPS54 in 9, 3, 12, 3, 5, 9, 2, and 2
      cancers, respectively, all in cancers with high microsatellite instability. The
      gastric cancers and colorectal cancers with high microsatellite instability
      harbored one or more mutations of the VPS genes in 53.3% and 50.0%, respectively.
      Loss of Vps13A expression was observed in 30% of the gastric cancers and 35% of
      the colorectal cancers, whereas loss of Vps35 was observed in 55% of the gastric
      cancers and 55% of the colorectal cancers. Our data indicate that frameshift
      mutations of VPS genes and losses of expression of Vps13A and Vps35 proteins are
      common in gastric cancers and colorectal cancers with high microsatellite
      instability and suggest that these alterations might contribute to development of
      cancers with high microsatellite instability by deregulating vacuolar protein
      sorting proteins.

PMID- 21733562
TI  - High prevalence of wild-type transthyretin deposition in patients with idiopathic
      carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly.
AB  - Carpal tunnel syndrome is the most common type of entrapment neuropathy. However,
      the cause of carpal tunnel syndrome remains unclear in most cases. Senile
      systemic amyloidosis, induced by wild-type transthyretin deposition, is a
      prevalent aging-related disorder and often accompanied by carpal tunnel syndrome.
      In this study, we measured the frequency of unrecognized wild-type transthyretin
      deposition in patients with idiopathic carpal tunnel syndrome. One hundred twenty
      three patients with carpal tunnel syndrome, including 100 idiopathic patients,
      treated by carpal tunnel release surgery were analyzed. Tenosynovial tissues
      obtained at surgery were analyzed by Congo red and immunohistochemical staining.
      If staining for transthyretin was positive, the entire transthyretin gene was
      analyzed by direct DNA sequencing. We also analyzed tenosynovial tissues from 32
      autopsy cases as controls. Thirty-four patients (34.0%) with idiopathic carpal
      tunnel syndrome showed amyloid deposition in the tenosynovial tissue, and all
      amyloid showed specific immunolabeling with antitransthyretin antibody. Direct
      DNA sequencing of the entire transthyretin gene did not reveal any mutations,
      indicating that all amyloid deposits were derived form wild-type transthyretin.
      Statistical analysis using logistic regression showed that the prevalence of
      transthyretin deposition in the idiopathic carpal tunnel syndrome group was
      significantly higher than that in controls (odds ratio, 15.8; 95% confidence
      interval, 3.3-5.7), and age and male sex were independent risk factors for
      transthyretin amyloid deposition. Our results demonstrate that wild-type
      transthyretin deposition is a common cause of carpal tunnel syndrome in elderly
      men. It is likely that many patients develop carpal tunnel syndrome as an initial
      symptom of senile systemic amyloidosis.

PMID- 21733563
TI  - Hepatocyte nuclear factor 4A expression discriminates gastric involvement by
      metastatic breast carcinomas from primary gastric adenocarcinomas.
AB  - Breast carcinomas sometimes metastasize to the stomach, and the histopathologic
      distinction of such metastases from primary gastric adenocarcinomas is often
      difficult. We characterized the clinicopathologic features of 21 breast
      carcinomas that had metastasized to the stomach and examined the use of a panel
      of antibodies, including hepatocyte nuclear factor 4A, for distinguishing the
      metastases from primary gastric diffuse-type adenocarcinomas. Histologically, all
      the metastatic breast carcinomas showed a poorly differentiated and/or signet
      ring cell morphology. Although most metastatic breast and primary gastric
      carcinomas contained signet ring cell components, the cases that were
      predominantly or exclusively composed of univacuolated-type signet ring cells
      were limited to metastatic breast carcinomas. Immunohistochemically, hepatocyte
      nuclear factor 4A was expressed in all 33 primary gastric carcinomas that were
      examined but was never expressed in metastatic breast carcinomas. Previously
      reported markers for breast and gastric carcinomas also showed a high
      specificity, but their sensitivities were quite variable. Estrogen receptor
      alpha, progesterone receptor, mammaglobin, and gross cystic disease fluid protein
      15 were expressed in 76%, 33%, 52%, and 62%, respectively, of the metastatic
      breast carcinomas, whereas none of the primary gastric carcinomas expressed these
      antigens. CDX2, MUC5AC, MUC6, and CK20 were expressed in 36%, 85%, 27%, and 55%,
      respectively, of the primary gastric carcinomas. All the metastatic breast
      carcinomas were negative for these antibodies except for 1 case that expressed
      MUC5AC. Overall, the use of immunohistochemistry efficiently discriminated
      metastatic breast carcinomas from primary gastric carcinomas. In particular, the
      present study identified hepatocyte nuclear factor 4A as an excellent marker for
      differentiating the 2 lesions.

PMID- 21733564
TI  - Development of a framework based on an ecosystem services approach for deriving
      specific protection goals for environmental risk assessment of pesticides.
AB  - General protection goals for the environmental risk assessment (ERA) of plant
      protection products are stated in European legislation but specific protection
      goals (SPGs) are often not precisely defined. These are however crucial for
      designing appropriate risk assessment schemes. The process followed by the Panel
      on Plant Protection Products and their Residues (PPR) of the European Food Safety
      Authority (EFSA) as well as examples of resulting SPGs obtained so far for
      environmental risk assessment (ERA) of pesticides is presented. The ecosystem
      services approach was used as an overarching concept for the development of SPGs,
      which will likely facilitate communication with stakeholders in general and risk
      managers in particular. It is proposed to develop SPG options for 7 key drivers
      for ecosystem services (microbes, algae, non target plants (aquatic and
      terrestrial), aquatic invertebrates, terrestrial non target arthropods including
      honeybees, terrestrial non-arthropod invertebrates, and vertebrates), covering
      the ecosystem services that could potentially be affected by the use of
      pesticides. These SPGs need to be defined in 6 dimensions: biological entity,
      attribute, magnitude, temporal and geographical scale of the effect, and the
      degree of certainty that the specified level of effect will not be exceeded. In
      general, to ensure ecosystem services, taxa representative for the key drivers
      identified need to be protected at the population level. However, for some
      vertebrates and species that have a protection status in legislation, protection
      may be at the individual level. To protect the provisioning and supporting
      services provided by microbes it may be sufficient to protect them at the
      functional group level. To protect biodiversity impacts need to be assessed at
      least at the scale of the watershed/landscape.

PMID- 21733565
TI  - Relating nutrient and herbicide fate with landscape features and characteristics
      of 15 subwatersheds in the Choptank River watershed.
AB  - Excess nutrients and agrochemicals from non-point sources contribute to water
      quality impairment in the Chesapeake Bay watershed and their loading rates are
      related to land use, agricultural practices, hydrology, and pollutant fate and
      transport processes. In this study, monthly baseflow stream samples from 15
      agricultural subwatersheds of the Choptank River in Maryland USA (2005 to 2007)
      were characterized for nutrients, herbicides, and herbicide transformation
      products. High-resolution digital maps of land use and forested wetlands were
      derived from remote sensing imagery. Examination of landscape metrics and water
      quality data, partitioned according to hydrogeomorphic class, provided insight
      into the fate, delivery, and transport mechanisms associated with agricultural
      pollutants. Mean Nitrate-N concentrations (4.9 mg/L) were correlated positively
      with percent agriculture (R(2)=0.56) and negatively with percent forest
      (R(2)=0.60). Concentrations were greater (p=0.0001) in the well-drained upland
      (WDU) hydrogeomorphic region than in poorly drained upland (PDU), reflecting
      increased denitrification and reduced agricultural land use intensity in the PDU
      landscape due to the prevalence of hydric soils. Atrazine and metolachlor
      concentrations (mean 0.29 MUg/L and 0.19 MUg/L) were also greater (p=0.0001) in
      WDU subwatersheds than in PDU subwatersheds. Springtime herbicide concentrations
      exhibited a strong, positive correlation (R(2)=0.90) with percent forest in the
      WDU subwatersheds but not in the PDU subwatersheds. In addition, forested
      riparian stream buffers in the WDU were more prevalent than in the PDU where
      forested patches are typically not located near streams, suggesting an
      alternative delivery mechanism whereby volatilized herbicides are captured by the
      riparian forest canopy and subsequently washed off during rainfall.
      Orthophosphate, CIAT (6-chloro-N-(1-methylethyl)-1,3,5-triazine-2,4-diamine),
      CEAT (6-chloro-N-ethyl-1,3,5-triazine-2,4-diamine), and MESA (2-[(2-ethyl-6
      methylphenyl) (2-methoxy-1-methylethyl)amino]-2-oxoethanesulfonic acid) were also
      analyzed. These findings will assist efforts in targeting implementation of
      conservation practices to the most environmentally-critical areas within
      watersheds to achieve water quality improvements in a cost-effective manner.

PMID- 21733566
TI  - Intraperitoneal treatment with the trifunctional bispecific antibody Catumaxomab
      in patients with platinum-resistant epithelial ovarian cancer: a phase IIa study
      of the AGO Study Group.
AB  - OBJECTIVE: The aim of this study was to select the best catumaxomab regimen for
      further investigation in ovarian cancer based on confirmed tumour response.
      METHODS: Randomised open-label phase IIa study in women with platinum-resistant
      or -refractory epithelial ovarian cancer. Catumaxomab (6-hour intraperitoneal
      infusion on days 0, 3, 7 and 10) was administered at a low (10, 10, 10 and 10
      MUg) or high dose (10, 20, 50 and 100 MUg). Responders were patients with either
      a complete (CR) or partial (PR) response. RESULTS: Forty-five patients were
      randomised to receive either low dose (23) or high dose (22). There were no
      responders in the low-dose versus one patient (5%) in the high-dose group with a
      PR. In the low-dose group, two patients (9%) had stable disease compared with
      five patients (23%) in the high-dose group. Catumaxomab was well tolerated and
      there was no difference between the dose groups in the incidence of treatment
      induced adverse events, the most common of which were gastrointestinal and
      injection-site reactions. CONCLUSION: Catumaxomab had modest activity in platinum
      resistant ovarian cancer. The high-dose regimen was associated with a slightly
      better therapeutic index than the low dose regimen.

PMID- 21733568
TI  - Interparental conflict and early adolescents' aggression: is irregular sleep a
      vulnerability factor?
AB  - We investigated whether (a) short and irregular sleep are related to aggressive
      behavior in early adolescence and (b) whether they moderate the relation between
      interparental conflict and aggressive behavior. 176 early adolescents (mean age
      11.6 years, 89 girls) reported their bed and wake times on weekdays and on
      weekends and their aggressive behavior. Interparental conflict was rated by their
      mothers and adolescents reported whether they felt threatened by the conflict. No
      direct association between early adolescents' sleep and aggression was found.
      However, short sleep duration on weekday nights, long sleep duration on weekends,
      and a large weekday to weekend difference in sleep duration moderated the
      relation between interparental conflict and early adolescents' aggression.
      Findings are consistent with the hypothesis that irregular sleep is a
      vulnerability factor for early adolescents' aggression and underscore the
      importance of sufficient and regular sleep for resilience.

PMID- 21733569
TI  - Retroperitoneal fibrosis: gaining traction on an enigma.

PMID- 21733570
TI  - Prednisone versus tamoxifen in patients with idiopathic retroperitoneal fibrosis:
      an open-label randomised controlled trial.
AB  - BACKGROUND: Glucocorticoids are the mainstay of treatment of idiopathic
      retroperitoneal fibrosis, but they often have substantial toxic effects. Several
      reports have suggested tamoxifen as an alternative to glucocorticoids. We
      compared the efficacy of prednisone with that of tamoxifen in maintainance of
      remission in patients with idiopathic retroperitoneal fibrosis. METHODS: In this
      open-label, randomised controlled trial, we enrolled patients aged 18-85 years
      with newly diagnosed idiopathic retroperitoneal fibrosis at the Parma Hospital,
      Parma, Italy, between Oct 1, 2000, and June 30, 2006. After induction therapy
      with 1 mg/kg daily of prednisone for 1 month, the patients who achieved remission
      were randomly assigned to receive tapering prednisone (initial dose 0.5 mg/kg
      daily) for 8 months or tamoxifen (fixed dose 0.5 mg/kg daily) for 8 months. The
      sequence of randomisation (1:1), blocked in groups of two and four (with block
      size randomly selected), was generated by the trial statistician with a computer
      programme. After the end of treatment, the patients were followed up for an
      additional 18 months. Neither patients nor those giving interventions or
      analysing the data were masked to group assignment. The two radiologists who
      assessed CT and MRI scans were masked. The primary endpoint was the relapse rate
      by the end of treatment (month 8), which was analysed by intention to treat. This
      trial is registered with ClinicalTrials.gov, number NCT00440349. FINDINGS: After
      induction therapy, 36 of the 40 enrolled patients achieved remission and were
      randomly assigned to treatment (18 per group). One patient (6%) in the prednisone
      group and seven patients (39%) in the tamoxifen group relapsed by the end of
      treatment (difference -33% [95% CI -58 to -8, p=0.0408]. The difference in
      relapse rate between the groups was sustained after the additional 18-month
      follow-up: the 26-month estimated cumulative relapse probability was 17% with
      prednisone and 50% with tamoxifen (difference -33% [-62 to -3, p=0.0372]).
      Cushingoid changes and grade 2 hypercholesterolaemia were more common in the
      prednisone group than in the tamoxifen group (p=0.0116 and p=0.0408,
      respectively). INTERPRETATION: Prednisone is more effective in prevention of
      relapses than is tamoxifen in patients with idiopathic retroperitoneal fibrosis.
      Therefore, prednisone should be considered as first-line treatment for patients
      with newly diagnosed idiopathic retroperitoneal fibrosis. FUNDING: Parma
      University Hospital.

PMID- 21733571
TI  - Effects of TiO2 nanotubes with different diameters on gene expression and
      osseointegration of implants in minipigs.
AB  - Titanium dioxide (TiO(2)) nanotubes can accelerate the adhesion and
      differentiation of osteoblasts, yet little is known how this nano-modified
      implant surface affects osseointegration at molecular level in vivo. The aim of
      this study was to investigate the effects of TiO(2) nanotubes with different
      diameters (30 nm, 70 nm and 100 nm) on biological attachment mechanism of
      implants to bone in vivo by studying the gene expression and bone formation
      around the implants. The histological features and fluorochrome labeling changes
      of bone around implants on the non-decalcified sections (at 3, 5 and 8 weeks
      after implantation) were investigated by using traditional light- and fluorescent
      microscopy, and the gene expression of alkaline phosphatase (ALP), osterix (Osx),
      collagen-I (Col-I) and tartrate-resistant acid phosphatase (TRAP) was examined by
      using real-time PCR at 1, 2, 3, 4 and 5 weeks after implantation. Comparing with
      machined titanium implants, a significant increase in bone-implant contact (BIC)
      and gene expression levels was found in the bone attached to implants with TiO(2)
      nanotubes, especially with 70 nm diameter nanotubes. At the same time, the
      sequential fluorescent labeling images illustrated dynamic bone deposition. In
      conclusion, TiO(2) nanotubes can modulate bone formation events at the bone
      implant interface as to reach favorable molecular response and osseointegration;
      in addition, the diameters of nanotubes can be precisely controlled in order to
      obtain better bone formation.

PMID- 21733572
TI  - Self-assembled nanoparticles based on hyaluronic acid-ceramide (HA-CE) and
      Pluronic(r) for tumor-targeted delivery of docetaxel.
AB  - Hyaluronic acid-ceramide (HA-CE)-based self-assembled nanoparticles were
      developed for intravenous docetaxel (DCT) delivery. In this study,
      physicochemical properties, cellular uptake efficiency, and in vivo targeting
      capability of the nanoparticles developed were investigated. DCT-loaded
      nanoparticles composed of HA-CE and Pluronic 85 (P85) with a mean diameter of 110
      140 nm were prepared and their morphological shapes were assessed using
      transmission electron microscopy (TEM). DCT release from nanoparticle was
      enhanced with increasing P85 concentrations in our in vitro model. Blank
      nanoparticles exhibited low cytotoxicity in U87-MG, MCF-7 and MCF-7/ADR cell
      lines. From cellular uptake studies, the nanoparticles developed enhanced the
      intracellular DCT uptake in the CD44-overexpressing cell line (MCF-7). The
      nanoparticles were shown to be taken up by the HA-CD44 interaction according to
      DCT and coumarin 6 (C6) cellular uptake studies. The multidrug resistance (MDR)
      overcoming effects of DCT-loaded HA-CE/P85-based nanoparticles were also observed
      in cytotoxicity tests in MCF-7/ADR cells. Following the intravenous injection of
      DCT-loaded cyanine 5.5 (Cy5.5)-conjugated nanoparticles in MCF-7/ADR tumor
      bearing mice, its in vivo targeting for CD44-overexpressing tumors was identified
      by non-invasive near-infrared (NIR) fluorescence imaging. These results indicate
      that the HA-CE-based nanoparticles prepared may be a promising anti-cancer drug
      delivery system through passive and active tumor targeting.

PMID- 21733573
TI  - Wharton's Jelly stem cells: future clinical applications.
AB  - This review focuses on the therapeutic potential of stem cells harvested from the
      Wharton's Jelly of the human umbilical cord. Recently, investigators have found
      that a potent stem cell population exists within the Wharton's Jelly. In this
      review, the authors define a new subset of stem cells, termed perinatal stem
      cells, and compare them to other sources of stem cells. Furthermore,
      cryopreservation of Wharton's Jelly stem cells is described for potential use in
      future cell based therapies and/or regenerative medicine applications. Current
      evidence of the application of mesenchymal stem cells from various sources in
      both pre-clinical and clinical trials is reviewed in the context of potential
      indications of use for Wharton's Jelly derived mesenchymal stem cells.

PMID- 21733574
TI  - A case of confined placental mosaicism with double trisomy associated with
      stillbirth.
AB  - We present a case of stillbirth in which the fetus was well grown and
      karyotypically normal, but the placenta was morphologically abnormal and had
      confined placental mosaicism (CPM) for a double trisomy of chromosomes 12 and 15.
      A compilation of published cases of CPM reveals that whilst approximately 80% of
      pregnancies progress normally, there is an association with abnormal placental
      morphology, intrauterine growth restriction, fetal abnormalities and stillbirth.
      This case highlights the potential adverse effects of CPM and the benefit of
      placental examination in determining the cause of stillbirth.

PMID- 21733575
TI  - Body feathers as a potential new biomonitoring tool in raptors: a study on
      organohalogenated contaminants in different feather types and preen oil of West
      Greenland white-tailed eagles (Haliaeetus albicilla).
AB  - We investigated the variation in concentrations and profiles of various classes
      of organohalogenated compounds (OHCs) in different feather types, muscle tissue
      and preen oil from 15 white-tailed eagle (Haliaeetus albicilla) carcasses from
      Greenland. The influence of moult patterns and potential external contamination
      onto the feather surface was examined, while the present study is also the first
      to investigate the use of body feathers for OHC monitoring. Concentrations of sum
      polychlorinated biphenyls (PCBs) in feathers from white tailed eagles ranged from
      2.3 ng/g in a primary wing feather to 4200 ng/g in body feathers. Using 300 mg of
      body feathers, almost 50 different OHCs could be quantified and median
      concentrations in body feathers were 10 fold higher than concentrations in tail
      feathers (rectrices) or primary wing feathers. Body feathers could be very useful
      for biomonitoring taking into account their easy sampling, short preparation time
      and high levels of OHCs. In addition, the effects of confounding variables such
      as feather size, moult and age are also minimised using body feathers.
      Correlations with concentrations in muscle tissue and preen oil were high and
      significant for all feather types (r ranging from 0.81 to 0.87 for sum PCBs).
      Significant differences in concentrations and profiles of OHCs were found between
      different primary feathers, indicating that the accumulation of OHCs in feathers
      varies over the moulting period (maximum three years). Washing of feathers with
      an organic solvent (acetone) resulted in a significant decrease in the measured
      concentrations of OHCs in feathers. However, our results indicated that preen oil
      is probably not the only contributor to the external contamination that can be
      removed by washing with acetone. Possibly dust and other particles may be of
      importance and may be sticking to the preened feathers. Rectrices washed only
      with water showed high and significant correlations with concentrations in muscle
      and preen oil as well. Washing with acetone therefore does not seem to be of
      great influence when relating to internal tissue concentrations. We recommend
      washing feathers only with distilled water in order to remove dirt and dust
      particles before analysis.

PMID- 21733576
TI  - The incidence and prevalence of admissions for melancholia in two cohorts (1875
      1924 and 1995-2005).
AB  - BACKGROUND AND METHOD: There have been recent proposals to have melancholia
      reinstated in classification systems as a disorder distinct from major depressive
      disorder. Data from two epidemiologically complete cohorts of patients presenting
      to mental health services in North Wales between 1875-1924 and 1995-2005 have
      been used to map the features of melancholia. RESULTS: The data point to a
      decline in the contemporary incidence of hospital admissions for depressive
      psychosis, and greater heterogeneity among hospitalized severe non-psychotic
      depressions today. They indicate that historically untreated episodes of
      "melancholia" had a sudden onset, an average duration of less than 6 months and a
      lesser likelihood of relapse than severe depressive disorders have today.
      LIMITATIONS: This is a study of the hospitalized illness rather than the natural
      illness and the relationship between illness and being hospitalized remains at
      present poorly understood. CONCLUSIONS: These are the first data on the
      comparative incidence and natural history of melancholia in historical and
      contemporary samples. They point to the distinctiveness of the condition and
      support arguments for its separation from other mood disorders.

PMID- 21733577
TI  - Enhanced stress analgesia to a cognitively demanding task in patients with
      posttraumatic stress disorder.
AB  - BACKGROUND: Uncontrollable stress is frequently accompanied by a primarily opioid
      mediated stress analgesia. In posttraumatic stress disorder (PTSD) exaggerated
      stress-induced analgesia to trauma reminders was proposed. The present study
      investigated whether enhanced analgesia occurs in response to a trauma-unrelated
      cognitive stressor in PTSD. METHODS: Functional magnetic resonance imaging data
      were obtained from fourteen outpatients with PTSD and 14 trauma-exposed subjects
      without PTSD (NPTSD) during mechanical painful stimulation before and after
      stress. Blood oxygenation level-dependent (BOLD) responses were assessed during
      painful stimulation. Pain ratings, pain thresholds and pain tolerance were
      assessed pre- and post-stress. Heart rate and blood pressure were recorded
      before, during and after stress. RESULTS: In comparison to NPTSD, PTSD-patients
      showed significantly more analgesia in terms of an increase of pain threshold and
      tolerance and a decrease in pain ratings after the stressor. Post-stress, PTSD
      patients compared to NPTSD displayed more activation of the rostral anterior
      cingulate cortex and decreased neural activity in brain areas associated with
      pain perception. However heart rate increase during stress and blood pressure
      decrease post-stress was lower in PTSD pointing to a dysregulation of the
      cardiovascular system in response to stress. LIMITATIONS: The small sample size
      represents a limiting factor in interpreting the results and might have led to
      low levels of significance for the group differences in BOLD response changes.
      CONCLUSIONS: These findings show enhanced stress reactivity and accompanying
      reduced pain perception in PTSD-patients in contrast to traumatized participants
      without PTSD. The results suggest that the previously reported enhanced analgesic
      response after trauma-related stress in PTSD transfers to trauma-unrelated
      stressors.

PMID- 21733578
TI  - Maternal background strain influences fetal-maternal trafficking more than
      maternal immune competence in mice.
AB  - The objective of this study was to determine if fetal-maternal cell trafficking
      is affected by maternal immune competence and/or parental background strain using
      fluorescence-activated cell sorting (FACS). In our experience the sensitivity of
      FACS allows for the detection of 5 fetal in 10(7) maternal cells and assessment
      of cell surface phenotype. Wild-type C57BL/6J (n=18), FVB/NJ (n=15), and
      immunodeficient B6129S7-Rag1(tm1Mom)/J (n=16) female mice were mated to C57BL/6J
      males homozygous for the green fluorescent protein (GFP) transgene. Single cell
      suspensions of maternal lung, liver, spleen, bone marrow, and blood were analyzed
      between late gestation (day e16-18) and 1 day post-partum for the number of GFP
      positive fetal cells in relation to 10(7) maternal cells and the percentage of
      GFP-positive cells that expressed the surface markers CD11b, CD29, CD34, CD44, or
      CD105. The highest relative proportions of GFP-positive fetal cells were observed
      in maternal lungs and livers from immunocompetent allogenic females. Among
      congenic matings, fetal cell microchimerism was higher in immunodeficient
      compared with immunocompetent females. Maternal strain and strain differences
      between the mother and father statistically significantly affected both the
      numbers of fetal cells and the relative distribution of cell types in maternal
      organs. The highest relative proportion of fetal cells was observed in allogenic
      matings with immunocompetent females. Since allogenic matings are more similar to
      those that occur in humans, future studies using animal models of microchimerism
      should consider incorporating this type of experimental design.

PMID- 21733579
TI  - Maternal history of depression is associated with enhanced theory of mind in
      depressed and nondepressed adult women.
AB  - Theory of mind forms the basis of social cognition and develops on a stereotyped
      ontogenetic timetable. Yet, there are individual differences in theory of mind
      that may be transmitted through genetic and/or environmental mechanisms. In the
      current study we examined the relation of maternal history of depression to
      individual differences in theory of mind in a sample of adult women. Sixty-one
      depressed women (23% with a positive maternal history of depression) and 30 non
      depressed women (33% with a positive maternal history of depression) completed
      the 'Reading the Mind in the Eyes task', a test of theory of mind decoding. Women
      with a maternal history of depression performed better on the Eyes task than
      those without. Further, the younger the mother's onset of depression, the better
      the current probands' Eyes task performance. These results are consistent with a
      broader literature linking hypersensitive social cognition and depression risk.
      We discuss the potential clinical implications of our results.

PMID- 21733580
TI  - Socio-cognitive-behavioral structural equation model of internalized stigma in
      people with severe and persistent mental illness should include personality
      dimensions.

PMID- 21733581
TI  - Association between smoking and outcomes in older adults with atrial
      fibrillation.
AB  - Tobacco smoking is a risk factor for atrial fibrillation (AF), but little is
      known about the impact of smoking in patients with AF. Of the 4060 patients with
      recurrent AF in the Atrial Fibrillation Follow-up Investigation of Rhythm
      Management (AFFIRM) trial, 496 (12%) reported having smoked during the past two
      years. Propensity scores for smoking were estimated for each of the 4060 patients
      using a multivariable logistic regression model and were used to assemble a
      matched cohort of 487 pairs of smokers and nonsmokers, who were balanced on 46
      baseline characteristics. Cox and logistic regression models were used to
      estimate the associations of smoking with all-cause mortality and all-cause
      hospitalization, respectively, during over 5 years of follow-up. Matched
      participants had a mean age of 70 +/- 9 years (+/- S.D.), 39% were women, and 11%
      were non-white. All-cause mortality occurred in 21% and 16% of matched smokers
      and nonsmokers, respectively (when smokers were compared with nonsmokers, hazard
      ratio=HR=1.35; 95% confidence interval=95%CI=1.01-1.81; p=0.046). Unadjusted,
      multivariable-adjusted and propensity-adjusted HR (95% CI) for all-cause
      mortality associated with smoking in the pre-match cohort were: 1.40 (1.13-1.72;
      p=0.002), 1.45 (1.16-1.81; p=0.001), and 1.39 (1.12-1.74; p=0.003), respectively.
      Smoking had no association with all-cause hospitalization (when smokers were
      compared with nonsmokers, odds ratio=OR=1.21; 95%CI=0.94-1.57, p=0.146). Among
      patients with AF, a recent history of smoking was associated with an increased
      risk of all-cause mortality, but had no association with all-cause
      hospitalization.

PMID- 21733582
TI  - Examination of balance ability evaluated by a stipulated tempo step test.
AB  - This study is aimed at examining the correlation between age and gait time using
      a Single-leg forward step (SFS) test. Two groups consisting of sixty healthy
      elderly women (age 71.4 +/- 6.4 years) and twenty young women (age 20.2 +/- 0.9
      years) performed the step test. The test subjects put one leg forward and
      returned it to its original position while matching varying metronome tempos (40
      bpm, 60 bpm, and 120 bpm) for 10s. As an evaluation parameter, the time
      difference between the metronome sound and the time when the subject's foot hits
      the ground was used. A significant time difference was found only in the group of
      elderly women. The time differences were greater in the 40 bpm and 120 bpm step
      tests than in the 60 bpm step test. The time variances showed significantly low
      correlations with gait time (r=0.33-0.42). Since the SFS test purposefully
      produces balance instability via shifts in one's center of gravity through
      forward and backward movements, the elderly with inferior balancing ability as
      well as a diminished ability to walk might have difficulty succeeding in this
      test. In conclusion, the SFS test is deemed effective in evaluating elderly
      subjects' balancing ability.

PMID- 21733583
TI  - Left ventricular non-compaction benefit from cardiac resynchronization therapy.

PMID- 21733584
TI  - Longitudinal investigation of protozoan parasites in meat lamb farms in southern
      Western Australia.
AB  - In this study, 96 faecal samples were collected from pregnant Merino ewes, at two
      broad-acre, commercial sheep farms in southern Western Australia, on two separate
      occasions (16 and 2 weeks prior to lambing). Following lambing, 111 (Farm A) and
      124 (Farm B) female crossbred lambs (2-6 weeks old), were individually identified
      using ear tags (a numbered tag and a radio-frequency tag). A total of 1155 faecal
      samples were collected only from these individually identified lambs on five
      separate sampling occasions. All samples were screened using PCR to detect
      Cryptosporidium (18S rRNA and actin loci) and Giardia duodenalis (glutamate
      dehydrogenase and triosephosphate isomerise loci). The overall prevalences (lambs
      positive for a parasite on at least one of the five samplings) at Farm A and B
      were 81.3% and 71.4%, respectively for Cryptosporidium and similarly 67.3% and
      60.5% for Giardia, respectively. Cryptosporidium and Giardia prevalences at
      individual samplings ranged between 18.5 and 42.6% in lambs and were <10% in the
      ewes. Cryptosporidium xiaoi was the most prevalent species detected at all five
      samplings and was also isolated from lamb dam water on Farm B. Cryptosporidium
      ubiquitum was most commonly detected in younger lambs and Cryptosporidium parvum
      was detected in lambs at all five samplings, typically in older lambs and as part
      of a mixed species infection with C. xiaoi. A novel, possibly new genotype (sheep
      genotype I), was identified in six Cryptosporidium isolates from Farm B. Giardia
      duodenalis assemblage E was the most common genotype detected at all five
      samplings, with greater proportions of assemblage A and mixed assemblage A and E
      infections identified in older lambs. This longitudinal study identified high
      overall prevalences of Cryptosporidium and Giardia in lambs grazed extensively on
      pastures, while reinforcing that sampling a random selection of animals from a
      flock/herd on one occasion (point prevalence), underestimates the overall
      prevalence of these parasites in the flock/herd across an extended time period.
      Based on these findings, grazing lambs were identified as a low risk source of
      zoonotic Cryptosporidium and Giardia species/genotypes, with these protozoa
      detected at all five samplings in some lambs, indicating that these individuals
      were either unable to clear the naturally acquired protozoan infections or were
      repeatedly re-infected from their environment or other flock members.

PMID- 21733585
TI  - Prevalence and risk factor analysis of livestock associated MRSA-positive pig
      herds in The Netherlands.
AB  - In 2005, methicillin-resistant Staphylococcus aureus was found in pig herds and
      in humans in contact with pigs. To determine the prevalence of, this now-called
      livestock-associated (LA) MRSA among pig herds in The Netherlands and to identify
      and quantify risk factors, an observational study of 202 pig herds was performed
      between 2007 and 2008. Five environmental wipes and 60 nasal swabs from each herd
      were collected, and microbiological analysis was performed on single
      environmental samples and pooled nasal samples. A herd was considered MRSA
      positive if >=1 sample tested positive. The prevalence of MRSA-positive herds was
      67% in breeding herds and 71% in finishing herds. Multivariable logistic
      regression analysis was then performed on data from 171 breeding herds. The
      number of MRSA-positive herds increased from ~30% at the start to ~75% at the end
      of the study, most likely due to transmission between herds. The prevalence of
      MRSA increased with herd size, as ~40% of smaller herds (<250 sows) were MRSA
      positive compared to >80% of larger herds (>500 sows). Other risk factors (e.g.
      antimicrobial use, purchase of gilts and hygiene measures) were not significantly
      associated with MRSA, though associated with herd size. Herd size appeared to be
      a compilation of several factors, which made larger herds more often MRSA
      positive.

PMID- 21733586
TI  - Factors associated with mortality of geriatric horses in the United Kingdom.
AB  - Geriatric horses (aged>=15 years) now represent a substantial proportion of the
      equine population, yet mortality rates for aged horses in the UK have not
      previously been described. Although post-mortem studies have provided some data
      regarding specific causes of death, "old age" is a common owner-reported reason
      for euthanasia of adult horses, indicating further elucidation of reasons for
      death or euthanasia is required for the geriatric equine population. The
      objective of this cohort study was to describe mortality rates, causes of death
      or euthanasia and factors associated with mortality in geriatric horses and
      ponies. Veterinary registered horses randomly selected for a cross-sectional
      questionnaire survey on geriatric health were enrolled in the cohort study
      (n=908). Follow-up information was obtained over an 18-month period via telephone
      questionnaires and mortality questionnaires, providing data regarding reasons for
      death or euthanasia, were completed for 118 cases of mortality. Overall and
      stratified mortality rates were calculated and Cox proportional hazards models
      were used to investigate risk factors associated with mortality. The majority
      (94%) of mortalities were euthanised, most frequently due to lameness (24%) and
      colic (21%). Veterinary advice was important in owner decision making regarding
      euthanasia of cases of colic or other acute illnesses, while poor quality of life
      was considered an important factor where euthanasia was due to chronic diseases
      or lameness. Overall mortality rate was 11.1 (95% C.I. 9.2-13.2) per 100 horse
      years at risk, with the mortality rate of animals >30 years of age over five
      times the rate in horses aged 15-19 years. On multivariable analysis, increasing
      age was associated with increasing mortality and Cob/Cob crossbreeds and
      Thoroughbred/Thoroughbred crossbreeds had an increased risk of mortality. Horses
      considered to be underweight had a greater risk of mortality than those in good
      condition. Increasing number of owner-reported clinical signs and the degree to
      which pain was reported to limit normal daily activities were associated with
      increased risk of mortality. The results of this study provide useful information
      about rates and factors associated with mortality in geriatric horses in the UK,
      which should be relevant to veterinary surgeons involved in the treatment of aged
      horses.

PMID- 21733587
TI  - Patient knowledge and antibiotic abuse: Evidence from an audit study in China.
AB  - We conduct an audit study in which a pair of simulated patients with identical
      flu-like complaints visits the same physician. Simulated patient A is instructed
      to ask a question that showcases his/her knowledge of appropriate antibiotic use,
      whereas patient B is instructed to say nothing beyond describing his/her
      symptoms. We find that a patient who displays knowledge of appropriate
      antibiotics use reduces both antibiotic prescription rates and drug expenditures.
      Such knowledge also increases physicians' information provision about possible
      side effects, but has a negative impact on the quality of the physician-patient
      interactions. Our results suggest that antibiotics abuse in China is not driven
      by patients actively demanding antibiotics, but is largely a supply-side
      phenomenon.

PMID- 21733588
TI  - Is being in school better? The impact of school on children's BMI when starting
      age is endogenous.
AB  - In this paper, we investigate the impact of attending school on body weight and
      obesity using a regression-discontinuity design. As is the case with academic
      outcomes, school exposure is related to unobserved determinants of weight
      outcomes because some families choose to have their child start school late (or
      early). If one does not account for this endogeneity, it appears that an
      additional year of school exposure results in a greater BMI and a higher
      probability of being overweight or obese. When we compare the weight outcomes of
      similar age children with one versus two years of school exposure due to
      regulations on school starting age, the significant positive effects disappear,
      and most point estimates become negative, but insignificant. However, additional
      school exposure appears to improve weight outcomes of children for whom the
      transition to elementary school represents a more dramatic change in environment
      (those who spent less time in childcare prior to kindergarten).

PMID- 21733589
TI  - Patent pools and clearinghouses in the life sciences.
AB  - The biopharmaceutical industry is slowly absorbing the idea of collaborative
      patent licensing models. Recently, two patent pools for developing countries have
      been launched: the Pool for Open Innovation against Neglected Tropical Diseases
      initiated by GlaxoSmithKline (GSK), which is referred to as the BIO Ventures for
      Global Health (BVGH) pool, and the Medicines Patent Pool (MPP) initiated by
      UNITAID. Various organizations have recommended using pools or clearinghouses
      beyond the humanitarian dimension where many patents are owned by many different
      actors. As a first attempt, MPEG LA, which administers patent pools in various
      technology fields, is now setting up a clearinghouse for patents related to
      molecular diagnostics. These examples as well as the results from an empirical
      study provide useful insights for the design and administration of future pools
      and clearinghouses in the life sciences.

PMID- 21733590
TI  - Applying usability heuristics to radiotherapy systems.
AB  - BACKGROUND AND PURPOSE: Heuristic evaluations have been used to evaluate safety
      of medical devices by identifying and assessing usability issues. Since
      radiotherapy treatment delivery systems often consist of multiple complex user
      interfaces, a heuristic evaluation was conducted to assess the potential safety
      issues of such a system. MATERIAL AND METHODS: A heuristic evaluation was
      conducted to evaluate the treatment delivery system at Princess Margaret Hospital
      (Toronto, Canada). Two independent evaluators identified usability issues with
      the user-interfaces and rated the severity of each issue. RESULTS: The evaluators
      identified 75 usability issues in total. Eighteen of them were rated as high
      severity, indicating the potential to have a major impact on patient safety. A
      majority of issues were found on the record and verify system, and many were
      associated with the patient setup process. While the hospital has processes in
      place to ensure patient safety, recommendations were developed to further
      mitigate the risks of potential consequences. CONCLUSIONS: Heuristic evaluation
      is an efficient and inexpensive method that can be successfully applied to
      radiotherapy delivery systems to identify usability issues and improve patient
      safety. Although this study was conducted only at one site, the findings may have
      broad implications for the design of these systems.

PMID- 21733591
TI  - Radiotherapy and oncology.

PMID- 21733592
TI  - Effect of high dose per pulse flattening filter-free beams on cancer cell
      survival.
AB  - PURPOSE: To investigate if there is a statistically significant difference in
      cancer cell survival using a high dose per pulse flattening filter-free (FFF)
      beam compared to a standard flattened beam. MATERIAL AND METHODS: To validate the
      radiobiological effect of the flattened and FFF beam, two glioblastoma cell lines
      were treated with either 5 or 10 Gy using different dose rates. Dose verification
      was performed and colony formation assays were carried out. To compare the
      predictability of our data, radiobiological models were included. RESULTS: The
      results presented here demonstrate that irradiation of glioblastoma cell lines
      using the FFF beam is more efficient in reducing clonogenic cell survival than
      the standard flattened beam, an effect which becomes more significant the higher
      the single dose. Interestingly, in our experimental setting, the radiobiological
      effect of the FFF beam is dependent on dose per pulse rather than on delivery
      time. The used radiobiological models are able to describe the observed dose rate
      dependency between 6 and 24 Gy/min. CONCLUSION: The results presented here show
      that dose per pulse might become a crucial factor which influences cancer cell
      survival. Using high dose rates, currently used radiobiological models as well as
      molecular mechanisms involved urgently need to be re-examined.

PMID- 21733593
TI  - Familial concordance of metabolic syndrome in Korean population--Korean National
      Health and Nutrition Examination Survey 2005.
AB  - AIMS: To investigate the familial concordance of metabolic syndrome and its
      components in a nationally representative survey in Korean. METHODS: We used data
      from the Korean National Health and Nutrition Examination Survey (KNHANES), a
      nationwide survey examining the general health and nutritional status of the
      Korean people. We enrolled 1641 married couples and 1527 parents-1342 offspring.
      RESULTS: Prevalence of the metabolic syndrome was 17.1% for husbands, 11.7% for
      wives, 14.3% for parents, and 7.2% for offspring. After adjustment for age, there
      were strong positive correlations between family members for the metabolic
      variables. Compared with husbands whose wives did not have metabolic syndrome,
      adjusted odds ratio in husbands whose wives had metabolic syndrome was 1.43 (95%
      CI: 1.10-1.87) for the risk of having metabolic syndrome. Similarly, wives whose
      husbands had metabolic syndrome had 1.41 (95% CI: 1.08-1.84) times higher risk of
      having metabolic syndrome. Compared with children whose parents did not have
      metabolic syndrome, adjusted odds ratio in children with at least one parent with
      the metabolic syndrome was 2.56 (95% CI: 1.09-5.98) for the metabolic syndrome.
      CONCLUSIONS: Our study revealed that there is significant familial concordance
      for metabolic syndrome and its components in Korean families.

PMID- 21733594
TI  - Co-existence of positive MET FISH status with EGFR mutations signifies poor
      prognosis in lung adenocarcinoma patients.
AB  - MET, a receptor tyrosine kinase for hepatocyte growth factor, is associated with
      tumor progression and acquired resistance to epidermal growth factor tyrosine
      kinase inhibitors (EGFR-TKI). Therefore, MET gene alterations could be both
      prognostic and predictive. Fluorescence in situ hybridization (FISH) is one
      method for assessing gene alteration, but the frequency of positive cases varies
      due to a lack of standardized criteria. We evaluated MET gene copy number in lung
      adenocarcinoma and its association with clinicopathological characteristics. FISH
      was applied to evaluate high MET gene copy number and true amplification in 138
      lung adenocarcinoma patients using two criteria: the Cappuzzo scoring system and
      PathVysion. MET positive cases according to the Cappuzzo scoring system evidenced
      both aneuploidy and true amplification, whereas PathVysion revealed only
      amplification. Proportion of MET FISH positive cases was 15% and 4% determined by
      the Cappuzzo system and PathVysion, respectively. PathVysion demonstrated higher
      frequencies of MET FISH positives among men and smokers and evidenced no MET FISH
      positives in patients with bronchioloalveolar carcinoma. Prognosis was
      significantly associated with MET FISH positive only as defined by the PathVysion
      system (gene amplification), not by the Cappuzzo system. However, progression
      free survival time of patients with both EGFR mutations and MET FISH positive
      defined by the Cappuzzo scoring system was significantly shorter than with EGFR
      mutations alone. These results suggest that MET FISH is a potential prognostic
      factor and coexistence of MET FISH with EGFR mutations signifies worse prognosis.

PMID- 21733595
TI  - Mast cells and histamine enhance the proliferation of non-small cell lung cancer
      cells.
AB  - Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with an
      extremely low survival rate. It is characterized by a chronic inflammatory
      process with intense mast cell infiltrate that is associated with reduced
      survival. The aim of this study was to test the hypothesis that mast cells have
      an enhancing effect on NSCLC proliferation. To assess the tumor-promoting
      potential of mast cells, we used the human alveolar basal adenocarcinoma (A549)
      and the mouse Lewis lung carcinoma (LLC) cell lines, umbilical cord blood-derived
      mast cells (CBMC) and the mast cell-deficient mouse Sash model. The proliferation
      rate of A549/LLC cells was markedly increased by mast cells and histamine.
      Histamine proliferating activity was mediated via H(1), H(2) and H(4) receptors
      and caused ERK phosphorylation. LLC induced in Sash mice or in wild-type mice
      treated with the mast cell stabilizer nedocromil sodium displayed an accelerated
      growth (number of metastic colonies in the lungs, total lung area and lung/total
      mice weight ratio). In summary, we have shown a significant effect of mast cells
      and histamine in enhancing NSCLC/LLCX growth in vitro, while in a mouse LLC model
      in vivo we have found that mast cells are important negative regulators of cancer
      development. Therefore our results would indicate a pro-tumorogenic effect of the
      mast cells in vitro on established lung tumor cell lines, and anti-tumorogenic
      effect in mice at lung cancer induction. In conclusion, mast cell/anti-histamine
      targeted therapies should carefully consider this dual effect.

PMID- 21733596
TI  - [Reversible posterior encephalopathy during pregnancy and/or puerperium in the
      intensive care unit].

PMID- 21733597
TI  - [A flagrant case of scientific fraud].

PMID- 21733598
TI  - [Epidemiological characteristics and types of domestic and leisure accidents:
      sentinel health network of Castilla y Leon (2009)].
AB  - OBJECTIVES: To study incidence, epidemiological characteristics and types of
      domestic and leisure accidents in Castilla y Leon during 2009. DESIGN: A
      descriptive study using a prospective sample design. EMPLACEMENT: Health Primary
      Care Centres of Castilla y Leon. PARTICIPANTS: The Nurse Registry is made up of
      130 nurses selected by conglomerates analysis. They cover 5% of the population.
      PRINCIPAL MEASUREMENTS: The information was obtained by means of an anonymous
      form. The studied variables were sex, age, type, place, type and origin of the
      accident. A descriptive analysis was performed using chi(2), Fischer, chi(2) of
      trends and t Student tests, with 95% confidence intervals. RESULTS: The annual
      cumulative incidence was 2651 cases/100000 inhabitants, there being slightly
      higher percentage of men (50.4%). The <= 15 and >= 65 years age groups had more
      accidents. The time of day of 49.2% of the accidents was during the morning and
      71.7% were on a working day. The majority (57.1%) took place in the home, 16,8%
      in the street, and 7.3% in schools. The most common accidents types were falls to
      the same level (40.4%) and use of cutting and sharp objects (22.7%). CONCLUSIONS:
      Most accidents took place within the home, on a working day and by falls. The
      most affected were the <= 15 and >= 65 years old age groups.

PMID- 21733599
TI  - [Referrals to a gastroenterology outpatient clinic from primary care: evaluation
      of two programs].
AB  - OBJECTIVES: To analyze the effect of implementing a high-resolution clinic (HRC)
      and an increasing resolution capacity program in primary care (IRCPPC) for
      referrals to a gastroenterology outpatient clinic from primary care and the
      resources used. METHODS: A retrospective and observational study based on a
      review of referral sheets and databases was performed. We analyzed the number and
      reason for referrals, delay times and resource consumption in two periods: before
      (first 4 months of 2007) and after (first 4 months of 2009) the launch of the
      IRCPPC and HRC. RESULTS: In the first and second periods, 881 and 1076 patients,
      respectively, referred from primary health care were evaluated in the
      gastroenterology clinic, with a decrease in the delay time in the second period
      (80.8 +/- 64.34 days vs 36.1 +/- 29.12 days, p < 0.001). The most frequent
      reasons for referral were dyspepsia (27.7%), high-risk of colorectal cancer
      (17.1%), disturbance of bowel rhythm (18.2%), abdominal pain (16%), and
      gastroesophageal reflux (11.2%), with no differences between the two periods.
      Although delay times until the first visit (10.8 +/- 9.03 days vs 42.8 +/- 28.67
      days, p < 0.001) and until discharge (39.6 +/- 80.65 days vs 128.6 +/- 135.34
      days, p < 0.001) were lower in referrals to the HRC, the number of visits (3.6 +/
      2.20 vs 3.2 +/- 1.95, p = 0.015) and the cost of referrals (592.7 +/- 421.50 ?
      vs 486.0 +/- 309.66 ?, p < 0.001) was higher. CONCLUSIONS: In the study period
      the number of referrals increased, while the delay time decreased. Although the
      HRC reduces delay times, it is associated with an increase in health resource
      use.

PMID- 21733600
TI  - [Importance of chronic musculoskeletal problems in the population of Catalonia
      (Spain): prevalence and effect on self-perceived health, activity restriction and
      use of health services].
AB  - OBJECTIVE: To determine the importance of chronic musculoskeletal problems in the
      adult population of Catalonia (Spain) and their effect on self-perceived health,
      activity restriction and use of health services. METHODS: A population-based
      survey of 15,926 adults was performed. Multistage stratified sampling was
      performed. The variables gathered were sociodemographic characteristics, self
      reported chronic health problems, self-perceived health, activity restriction and
      use of health services. Musculoskeletal problems were grouped into four
      categories: osteoarthritis-arthritis or rheumatism (OA), chronic dorsal or lumbar
      pain (LBP), chronic cervical pain (UBP), and osteoporosis. RESULTS: Chronic
      health problems were reported by 77.4% of the adult population. The most frequent
      health problem was LBP, followed by UBP and OA. After adjustment by age was
      performed, female sex increased the risk of reporting OA, LBP, UBP and
      osteoporosis (OR=2.6, 1.5, 2.3, and 5.3, respectively). The prevalence increased
      with greater age and with lower socioeconomic status. After adjustment was
      performed by age, sex, social class and obesity, self-perceived health was worse
      in people with these problems (42.7% vs 11%). The four categories were the main
      causes of activity restriction in the last year (OR 2.70) and the last 15 days
      (OR=2.32) and were associated with a higher use of health services. CONCLUSIONS:
      Los problemas reumaticos son los principales problemas de salud cronicos
      declarados por la poblacion adulta. La prevalencia es mayor es las mujeres,
      aumenta con la edad y en las clases desfavorecidas. Hay una asociacion
      significativa entre declarar problemas musculoesqueleticos y salud autopercibida
      mala o regular, y mayor restriccion de actividades y uso de servicios sanitarios.

PMID- 21733601
TI  - Synthesis and biological evaluation of derivatives of 4-deoxypodophyllotoxin as
      antitumor agents.
AB  - In an attempt to generate compounds with superior bioactivity and reduced
      toxicity, a series of derivatives of deoxypodophyllotoxin were synthesized by
      reacting 4'-demethyl-4-deoxypodophyllotoxin with substituted piperazines or their
      amino acid amides. The cytotoxic activity of these compounds against three human
      cancer cell lines was evaluated. We found that p-nitrophenylpiperazine
      substitution (Compound 8b) led to an increase in the potency of the compound.
      Compound 8b exhibited the most potent cytotoxicity against A-549, HeLa and SiHa
      cells (IC(50) values were 0.102, 0.180 and 0.0195 MUM, respectively). In
      addition, flow cytometric analysis showed that 8b induced cell cycle arrest in
      the G1 phase accompanied by apoptosis in A-549 cells.

PMID- 21733602
TI  - Educator as shaman and the sublated space.
AB  - This paper seeks to identify and explore some of the tensions that nurse
      educators face when engaging in the competing internal and external demands that
      are made on their delivery of curricula. It offers that one of the ways to
      explore these tensions constructively is to see them dialectically. It seeks to
      identify three archetypal dialectical themes that can be present in our teaching
      and offers that the educator's role can be understood to be one of a shaman as
      they seek to resolve these dialectical tensions skillfully.

PMID- 21733603
TI  - Oral citrulline does not affect whole body protein metabolism in healthy human
      volunteers: results of a prospective, randomized, double-blind, cross-over study.
AB  - BACKGROUND & AIMS: Citrulline increases protein synthesis during refeeding in
      rodents with short bowel syndrome, aging and malnutrition, and improves nitrogen
      balance in fed healthy humans. The aim of the current study therefore was to
      determine whether citrulline had affected protein metabolism in healthy
      volunteers. METHODS: In a randomized, double-blind, cross-over study, 12 healthy
      adults received a 5-h intravenous infusion of L-[1-(13)C]-leucine in the post
      absorptive state, after a 7-day oral supplementation with 0.18 g/kg/day
      citrulline, or an iso-nitrogenous placebo. Treatment order was randomized,
      treatment periods were separated by 13-day wash out. Leucine appearance rate (Ra)
      was determined from plasma [1-(13)C]-keto-iso-caproate enrichment and leucine
      oxidation from expired (13)CO(2), and nitrogen balance was estimated from 6-h
      urinary urea excretion. RESULTS: Compared with placebo, oral citrulline
      supplementation increased plasma citrulline, arginine and ornithine
      concentrations, but failed to affect albumin, transthyretin, free insulin and
      insulin-like growth factor (IGF)-1 plasma concentrations, urinary nitrate
      excretion, or nitrogen balance. Citrulline supplementation did not alter leucine
      Ra, leucine oxidation, nor whole-body protein synthesis. CONCLUSION: In healthy,
      well nourished volunteers, oral citrulline increases plasma citrulline and
      arginine availability but does not affect whole-body protein kinetics in the post
      absorptive state.

PMID- 21733604
TI  - Patient-focused endpoints in advanced cancer: criterion-based validation of
      accelerometer-based activity monitoring.
AB  - BACKGROUND & AIMS: Objective assessment of daily physical activity (PA) by body
      worn accelerometers offers potential as a novel endpoint in the clinical
      management of advanced cancer patients. This study aimed to assess criterion
      based validity of an accelerometer-based activity monitoring system (AM-system),
      ActivPALTM, using two different methods. METHODS: Advanced cancer in patients and
      outpatients (Karnofsky Performance Status (KPS) 40-100). ActivPALTM measurements
      were validated against (i) observations and (ii) energy expenditure (EE) measured
      by 2-week doubly-labelled water (DLW) protocol. RESULTS: Absolute errors for mean
      time spent in different body positions (<0.1%) and number of transfers (0%) were
      low. Step count error was significantly higher in patients with KPS 40-60 (non
      self caring) compared to KPS 70-100 (self-caring) (33 vs. 24%, p = 0.006). Post
      hoc mathematical analysis demonstrated that absolute errors for the mean energy
      expenditure of activity (EEA) (1.4%) and mean total EE (0.4%) were low, but
      agreement was also low. CONCLUSIONS: AM-systems provide valid estimates of body
      positions and transfers, but not step count, especially in non-self caring
      patients. ActivPALTM can derive estimates of EE but there is considerable
      variability in results, which is consistent, in part, with the inaccuracy in step
      count. Further studies are required to assess the validity of different endpoints
      derived from AM-systems in advanced cancer patients.

PMID- 21733605
TI  - Oral glutamine supplementation during preoperative radiochemotherapy in patients
      with rectal cancer: a randomised double blinded, placebo controlled pilot study.
AB  - BACKGROUND & AIMS: Enteral glutamine may have protective effects on gut function
      and reduce metabolic stress in patients receiving radiochemotherapy. The aim of
      our study was to evaluate its influence in patients with rectal cancer undergoing
      preoperative radiochemotherapy. METHODS: We performed a randomized double blind,
      placebo controlled pilot study in 33 patients. 30 g of glutamine, average dose
      0.41 g/kg (SD = 0.07) g/kg/day was administered orally in three doses per day for
      five weeks during preoperative radiochemotherapy of rectal cancer. 30 g of
      maltodextrin was given as placebo. Body weight was measured and NRS 2002
      screening was performed before and after treatment. Bowel function was evaluated
      by stool consistency and frequency. Plasma levels of inflammatory parameters and
      hormones were measured. RESULTS: There was no difference between groups in
      frequency and severity of diarrhoea during radiochemotherapy (p = 0.5 and p =
      0.39 respectively), insulin levels significantly increased in both groups, IL-6
      only in glutamine group. CONCLUSION: Results of this small pilot study in rectal
      cancer patients receiving preoperative radiochemotherapy, showed that ingestion
      of larger quantities of glutamine given more often as previously reported did not
      diminish the incidence and severity of diarrhoea and did not affect inflammatory
      and metabolic activity compared to the placebo treatment with maltodextrin.

PMID- 21733606
TI  - Exposure to moderate concentrations of tropospheric ozone impairs tree stomatal
      response to carbon dioxide.
AB  - With rising concentrations of both atmospheric carbon dioxide (CO(2)) and
      tropospheric ozone (O(3)), it is important to better understand the interacting
      effects of these two trace gases on plant physiology affecting land-atmosphere
      gas exchange. We investigated the effect of growth under elevated CO(2) and O(3),
      singly and in combination, on the primary short-term stomatal response to CO(2)
      concentration in paper birch at the Aspen FACE experiment. Leaves from trees
      grown in elevated CO(2) and/or O(3) exhibited weaker short-term responses of
      stomatal conductance to both an increase and a decrease in CO(2) concentration
      from current ambient level. The impairement of the stomatal CO(2) response by
      O(3) most likely developed progressively over the growing season as assessed by
      sap flux measurements. Our results suggest that expectations of plant water
      savings and reduced stomatal air pollution uptake under rising atmospheric CO(2)
      may not hold for northern hardwood forests under concurrently rising tropospheric
      O(3).

PMID- 21733607
TI  - Workaholism and well-being among Japanese dual-earner couples: a spillover
      crossover perspective.
AB  - This study among Japanese dual-earner couples examined the impact of workaholism
      on employees' and their partners' work-family conflicts and psychological
      distress. The matched responses of 994 couples were analyzed with logistic
      regression analyses. Results showed that workaholics (i.e., employees scoring
      high on both working excessively and working compulsively) were more likely to
      experience work-to-family conflict and psychological distress compared to relaxed
      workers (i.e., low on both working excessively and working compulsively) for both
      genders. Results also showed that husbands of workaholic women were more likely
      to experience family-to-work conflict, whereas wives of workaholic men were not.
      These findings integrate and expand previous findings on workaholism and the
      recently formulated spillover-crossover model.

PMID- 21733608
TI  - Biopolitical endpoints: diagnosing a deserving British nuclear test veteran.
AB  - This article examines recent claims for healthcare made by British veterans who
      participated in nuclear bomb testing in the 1950s. Specifically, it focuses on
      their claims for war disablement pensions, exploring how they seek and challenge
      medical diagnoses. Detailing three veteran case studies, the article offers an
      ethnographic analysis of illness narratives. It explores how sufferers attempt to
      recast and reject the evidential burdens that they face in pension appeals, and
      identifies three narratives strategies that they deploy aimed at linking somatic
      realities to political etiologies. I propose the notion of biopolitical endpoints
      to capture how test veterans narratively connect political and medical domains as
      they seek to enable state culpability and redress.

PMID- 21733609
TI  - Mothers' preferences and willingness to pay for HPV vaccines in Vinh Long
      Province, Vietnam.
AB  - About 530,000 women develop cervical cancer worldwide and 275,000 die from the
      disease each year. Eighty percent of these deaths occur in developing countries.
      In Vietnam, cervical cancer has recently emerged as the most common type of
      cancer in women, and there are no national screening programs for cervical
      cancer. Since 2009, two different human papillomavirus (HPV) vaccines have been
      licensed for use in Vietnam, but access to these vaccines is generally limited to
      people who live in urban areas. Studies have shown that HPV vaccination may be
      cost-effective in cervical cancer prevention in Vietnam, depending on vaccination
      costs. Given that current HPV vaccines are expensive and public health funding
      for supporting a rapid introduction of the vaccine is limited, expanding and
      sustaining access to the HPV vaccine may require alternative financing
      mechanisms, such as fees-based immunization services. A conjoint analysis study
      was conducted with mothers of girls 9-17 years of age in Vinh Long Province in
      Vietnam to estimate the mothers' demand for HPV vaccines for their daughters and
      to measure the tradeoffs between vaccine fees and vaccine uptake. The results
      suggest that the demand for HPV vaccines was high, increased with vaccine
      effectiveness and duration of effectiveness, and decreased with vaccine cost.
      Vaccine effectiveness was the most important vaccine attribute to these mothers,
      followed by duration of effectiveness. The predicted probability of respondents
      buying an HPV vaccine that was 70% effective for 10 years varied by the price,
      ranging from 30% when the vaccine price was $353 per course, to 68% when the
      vaccine cost $6 per course. As expected, demand and predicted purchase
      probability were higher among groups with higher socioeconomic status.

PMID- 21733610
TI  - Moving towards universal health insurance in China: performance, issues and
      lessons from Thailand.
AB  - China is now in the course of implementing a new round of health system reforms.
      Universal health insurance coverage through the basic social medical insurance
      system is high on the reform agenda. This paper examines the performance of
      China's current social medical insurance system in terms of revenue collection,
      risk pooling, the benefit package, and provider payment mechanisms based on a
      literature review and publicly available data. On the basis of critical
      assessment, the paper attempts to address the issues challenging China as it
      moves towards universal coverage. Focusing in particular on the reform experience
      in Thailand as it implemented universal coverage, the following policy
      implications for further reform in China are articulated, taking into account
      China's particular circumstances: firstly, the gaps in the benefit package across
      different schemes should be further reduced; secondly, the prevailing fee-for
      service payment system needs to be transformed; thirdly, the primary health care
      delivery and referral system needs to be strengthened in coordination with the
      reform of the health insurance system; and fourthly, raising the risk pooling
      level and integrating fragmented insurance schemes should be long-run objectives
      of reform.

PMID- 21733611
TI  - From cardiopulmonary to cardiorespiratory resuscitation.

PMID- 21733612
TI  - Severe controlled hemorrhage resuscitation with small volume poloxamer 188 in
      sedated miniature swine.
AB  - BACKGROUND: The surfactant poloxamer 188 (P188) has been shown to improve
      survival following hemorrhage. This study used P188 as a small volume
      resuscitation product in a sedated, sexually mature, male miniature swine severe
      hemorrhage model for potential improvement in rate and time of survival. METHODS:
      Fourteen swine were anesthetized, catheterized for hemorrhage and resuscitation
      and allowed to recover from anesthesia. The animals were sedated and hemorrhaged
      60% of estimated blood volume (~39 mlkg(-1)) exponentially over 1h. Following
      hemorrhage the animals were treated with either 1.33 mlkg(-1) of P188 (150 mgml(
      1); 7 swine) or the P188 citrate vehicle (7 swine) given as an i.v. infusion over
      2 min without additional resuscitation fluids. The data were compared with
      control data from sedated swine similarly hemorrhaged, but with no resuscitation
      (untreated; n=16). RESULTS: Median (95% CI) survival time for the untreated
      control swine was 55.8 (36.5-86) min with a 6% survival at 180 min. Median
      survival time of 161 (80-180) min for the P188 swine was significantly greater
      than control (p=0.0186), whereas the citrate vehicle median survival time of 91
      (32-180) min was not significantly different from control or P188. At the
      survival target time of 180 min, survival rates were not significantly different
      among the three groups. TEG data from swine demonstrated anti-coagulant
      properties of P188. This was confirmed with human blood ex vivo. CONCLUSION: In
      the presence of severe controlled hemorrhage, P188 improved median survival time.
      However, retardation of blood clotting raises concerns as to its use in the
      presence of uncontrolled hemorrhage.

PMID- 21733613
TI  - Intrapartum caesarean rates differ significantly between ethnic groups-
      relationship to induction.
AB  - OBJECTIVE: Given international variation in obstetric practices and outcomes,
      comparison of labour outcomes in different ethnic groups could provide important
      information regarding the underlying reasons for rising caesarean delivery rates.
      Increasing numbers of women from Eastern European countries are now delivering in
      Irish maternity hospitals. We compared labour outcomes between Irish and Eastern
      European (EE) women in a large tertiary referral center. STUDY DESIGN: This was a
      prospective consecutive cohort study encompassing a single calendar year. The
      cohort comprised 5550 Irish and 867 EE women delivered in a single institution in
      2009. Women who had multiple pregnancies, breech presentation, and elective or
      pre-labour caesarean sections (CS) were excluded. Data obtained from birth
      registers included maternal age, nationality, parity, gestation, onset of labour,
      mode of delivery and birth weight. RESULTS: The overall intrapartum CS rate was
      11.4% and was significantly higher in Irish compared to EE women (11.8% vs. 8.8%;
      p=0.008). The proportion of primiparas was lower in Irish compared to EE women
      (44.8% vs. 63.6%; p<0.0001). The intrapartum CS rate was almost doubled in Irish
      compared to EE primiparas (20.7% vs. 11.0%; p<0.0001). Analysis of primiparas
      according to labour onset revealed a higher intrapartum CS rate in Irish
      primiparas in both spontaneous (13.5% vs. 7.2%; p<0.0001) and induced labour
      (29.5% vs. 19.3%; p=0.005). Irish women were older with 19.7% of primiparas aged
      more than 35, compared to 1.6% of EE women (p<0.0001). The primigravid CS rate in
      Irish women was significantly higher in women aged 35 years or older compared
      women aged less than 35 (30.6% vs. 18.3%; p<0.0001) consistent in both
      spontaneous and induced labour. The primiparous induction rate was 45.4% in Irish
      women compared to 32% in EE women, and more Irish women were induced before 41
      weeks gestation. CONCLUSION: The results highlight that primigravid intrapartum
      CS rates were significantly lower in EE compared to Irish women. This could
      potentially be explained by the younger age and lower induction rates in EE
      primiparas. Further studies are required to determine the factors for this
      significant difference in labour outcomes for these two Caucasian groups.

PMID- 21733614
TI  - Does urinary incontinence subtype affect sexual function?
AB  - OBJECTIVE: Urinary incontinence (UI) may affect a woman's physical and
      psychological well-being in different aspects. The aim of this study was to
      compare the effects of urinary stress incontinence (USI), detrusor overactivity
      (DO) and mixed urinary incontinence (MUI) on sexual function. STUDY DESIGN: One
      hundred and seventy urinary incontinent, sexually active women were included in
      this cross-sectional study. After urodynamic evaluation, participants were
      divided into three subgroups as USI (n=61), DO (n=55) and MUI (n=54). Patients
      were matched according to age, parity and body mass index (BMI), rendering the
      sample size to 41 patients in each group. Turkish version short form of the
      Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire (PISQ-12) was
      filled out by each of the participants. Totally, 52 patients were excluded from
      the study (47 could not be matched and 5 incomplete questionnaire). Demographic
      characteristics of the participants, total and three domain scores of PISQ-12
      were compared among three UI subgroups. RESULTS: The study group was consisted of
      38 (32.2%) DO, 41 (34.7%) USI and 39 (33.1%) MUI patients. Demographic
      characteristics of the patients were similar in three subgroups. Patients with a
      diagnosis of MUI had significantly lower mean PISQ-12 scores than the ones with
      USI and DO whereas patients with USI had lower mean PISQ-12 scores than patients
      with DO. CONCLUSION: Although urinary stress incontinence effects sexual function
      more than detrusor overactivity in terms of PISQ-12 scores, mixed urinary
      incontinence has the greatest impact on sexual function when compared with
      urinary stress incontinence and detrusor overactivity.

PMID- 21733615
TI  - Adenomyosis and junctional zone changes in patients with endometriosis.
AB  - OBJECTIVES: To evaluate image findings in the junctional zone (JZ) in patients
      with endometriosis and correlate with image findings of adenomyosis. To attempt a
      correlation of the degree of adenomyotic infiltration with the degree of
      infiltration and stage of endometriosis. STUDY DESIGN: Magnetic resonance imaging
      (MRI) of the uterus was performed in 153 women with suspected deeply infiltrating
      endometriosis and planned surgery, and in a reference group of 129 women without
      endometriosis, verified during hysterectomy. Changes in the JZ and endometriosis
      in the pelvis were described in detail. Diagnosis of adenomyosis at MRI was based
      on optimal criteria derived from the hysterectomy control group. The stage of
      endometriosis (AFS stage) was determined during surgery. RESULTS: In the group of
      women with endometriosis 34.6% had adenomyosis compared with 19.4% in the
      reference group (p<0.05). More women with endometriosis (39.9%) had an irregular
      JZ compared to 22.5% in the reference group (p<0.01). Among women with severe
      endometriosis (AFS stage IV) 42.8% had adenomyosis compared to 29.4% in the women
      with other stages of endometriosis (AFS stages I+II+III) (p=0.10). More women
      with severe endometriosis (AFS stage IV) had deeper wall invasion of adenomyosis
      (p>0.05) but the presence of deep infiltrative rectovaginal endometriosis and the
      size of infiltration were not correlated to adenomyosis or depth of infiltration
      of adenomyosis. CONCLUSIONS: In a group of young women with severe symptomatic
      endometriosis and planned surgery a systematic evaluation of the JZ revealed that
      one third had uterine adenomyosis, but the invasive potential of endometrial
      cells in the uterus and in the peritoneum corresponded only to a limited degree.

PMID- 21733616
TI  - Transvaginal mesh (ProliftTM) repair: 2-year anatomic outcomes.
AB  - OBJECTIVE: The aim of our study was to report anatomic outcomes at 2 years in
      patients who underwent transvaginal mesh repair (ProliftTM) for pelvic organ
      prolapse (POP). STUDY DESIGN: We conducted a prospective study of 60 women who
      underwent surgery between April 2005 and March 2008 and presented for 2 year
      follow-up visits. RESULTS: Median follow-up was 29 months, and mean age was 57.5
      years. There were significant improvements in the Pelvic Organ Prolapse
      Quantification system (POP-Q) measurements of point C/D and the leading edge of
      the prolapse/most dependent part of the vagina (p<0.001). Overall anatomic
      success rate was 85%. Mesh exposure was seen in 15% of patients and there was
      recurrent prolapse in 10%. CONCLUSIONS: Women undergoing the ProliftTM procedure
      have a good anatomical success rate over the medium term. The higher mesh erosion
      rates seen in our study emphasises the need for long-term follow-up in these
      patients.

PMID- 21733617
TI  - Laparoscopic treatment of a tailgut cyst.

PMID- 21733618
TI  - Lenses for learning: visual techniques in natural resource management.
AB  - In this study, we explored the use of selected visual techniques (e.g. video,
      photography, diagramming) in facilitating learning among Indigenous communities
      living in remote protected areas at sites in Vietnam and Australia. The
      techniques were employed during interviews and workshops aimed at accessing and
      enhancing local peoples' perspectives on their landscape and on specific natural
      resource management issues. The effectiveness of the different techniques for
      enabling learning varied markedly with the context, highlighting the need for
      facilitator skill and flexibility in application of techniques. Visual techniques
      helped to engage participants; encourage unrestrained and lateral thinking;
      provide opportunities for self-expression and reflection; and to expose
      participants to perspectives of other community members. Valuable insights
      emerged on broad aspects of learning and these were incorporated into a simple
      model that highlights three types of conceptualisation found to be important in
      these processes.

PMID- 21733619
TI  - Reuse of sugarcane bagasse ash (SCBA) to produce ceramic materials.
AB  - Sugarcane bagasse ash (SCBA) is a residue resulting from the burning of bagasse
      in boilers in the sugarcane/alcohol industry. SCBA has a very high silica
      concentration and contains aluminum, iron, alkalis and alkaline earth oxides in
      smaller amounts. In this work, the properties of sintered ceramic bodies were
      evaluated based on the concentration of SCBA, which replaced non-plastic
      material. The ash was mixed (up to 60 wt%) with a clayed raw material that is
      used to produce roof tiles. Prismatic probes were pressed and sintered at
      different temperatures (up to 1200  degrees C). Technological tests of ceramic
      probes showed that the addition of ash has little influence on the ceramic
      properties up to 1000  degrees C. X-ray diffraction and thermal analysis data
      showed that, above this temperature the ash participates in the sintering process
      and in the formation of new important phases. The results reported show that the
      reuse of SCBA in the ceramic industry is feasible.

PMID- 21733620
TI  - Varicocele and male factor infertility treatment: a new meta-analysis and review
      of the role of varicocele repair.
AB  - CONTEXT: Varicocele is a common condition, found in many men who present for
      infertility evaluation. OBJECTIVE: To assess the effect of varicocelectomy on
      male infertility. EVIDENCE ACQUISITION: A literature search was performed using
      Embase and Medline. Literature reviewed included meta-analyses and randomized and
      nonrandomized prospective (controlled and noncontrolled) studies. In addition, a
      new meta-analysis was performed. EVIDENCE SYNTHESIS: Four randomized controlled
      trials reporting on pregnancy outcome after repair of clinical varicoceles in
      oligozoospermic men were identified. Using the random effect model, the combined
      odds ratio was 2.23 (95% confidence interval [CI], 0.86-5.78; p=0.091),
      indicating that varicocelectomy is moderately superior to observation, but the
      effect is not statistically significant. We identified 22, 17, and 5 prospective
      studies reporting on sperm concentration, total motility, and progressive
      motility, respectively, before and after repair of clinical varicocele. The
      random effect model combined improvement in sperm concentration was 12.32 million
      sperm per milliliter (95% CI, 9.45-15.19; p<0.0001). The random effect model
      combined improvement in sperm total and progressive motility were 10.86% (95% CI,
      7.07-14.65; p<0.0001) and 9.69% (95% CI, 4.86-14.52; p=0.003), respectively.
      These results indicate that varicocelectomy is associated with a significant
      increase in sperm concentration as well as total and progressive motility.
      Prospective studies also show that varicocelectomy reduces seminal oxidative
      stress and sperm DNA damage as well as improving sperm ultramorphology. Studies
      indicate that a microsurgical approach to a varicocele repair results in less
      recurrence and fewer complications than other techniques. CONCLUSIONS: Although
      there is no conclusive evidence that a varicocele repair improves spontaneous
      pregnancy rates, varicocelectomy improves sperm parameters (count and total and
      progressive motility), reduces sperm DNA damage and seminal oxidative stress, and
      improves sperm ultramorphology. The various methods of repair are all viable
      options, but microsurgical repair seems to be associated with better outcomes.

PMID- 21733621
TI  - Using laser to unobstruct the obstructed prostatic urethra due to benign
      prostatic hyperplasia: has transurethral resection of the prostate finally become
      history, or is it here to stay?

PMID- 21733623
TI  - Subcritical water extraction for the remediation of phthalate ester-contaminated
      soil.
AB  - Subcritical water has been used as an environment-friendly extraction fluid for
      many classes of organic compounds. It was used for the removal of phthalate
      esters (PEs), such as di-methyl phthalate, DMP; di-ethyl phthalate, DEP; di-iso
      propyl phthalate, DIPP; di-n-butyl phthalate, DBP; benzyl butyl phthalate, BBP;
      di-n-pentyl phthalate, DpentP; di-n-hexyl phthalate, DHXP; di-heptyl phthalate,
      DheptP; di-2-ethylhexyl phthalate, DEHP; di-n-nonyl phthalate, DNP; di-n-octyl
      phthalate, DOP; di-n-decyl phthalate, DDP, in soil samples under the optimum
      condition of 250  degrees C and 10 MPa in our study. The soil samples cleaned
      with subcritical water were extracted by homemade accelerated solvent extraction
      system (ASE) and analyzed by HPLC-UV to check for soil remediation efficiency.
      Three types of soil collected at different sites in Taiwan have been tested.
      Although at higher PEs concentration levels, the modification of treatments may
      be necessary for satisfactory removal of the contaminants, soil samples of
      different PEs levels treated with subcritical water extraction (SCWE) were
      analyzed and the results indicated removal efficiency ranges of 80-90% for PEs
      spiked in soil samples. Soil samples contaminated with native DEHP were treated
      and gave comparable recovery efficiencies. Our results indicate that the
      applications of subcritical water as soil remediation for removal of PEs
      contaminant are feasible.

PMID- 21733624
TI  - Decolorization of different dyes by a newly isolated white-rot fungi strain
      Ganoderma sp.En3 and cloning and functional analysis of its laccase gene.
AB  - A laccase-producing white-rot fungi strain Ganoderma sp.En3 was newly isolated
      from the forest of Tzu-chin Mountain in China. Ganoderma sp.En3 had a strong
      ability of decolorizing four synthetic dyes, two simulated dye bath effluents and
      the real textile dye effluent. Induction in the activity of laccase during the
      decolorization process indicated that laccase played an important role in the
      efficient decolorization of different dyes by this fungus. Phytotoxicity study
      with respect to Triticum aestivum and Oryza sativa demonstrated that Ganoderma
      sp.En3 was able to detoxify four synthetic dyes, two simulated dye effluents and
      the real textile dye effluent. The laccase gene lac-En3-1 and its corresponding
      full-length cDNA were then cloned and characterized from Ganoderma sp.En3. The
      deduced protein sequence of LAC-En3-1 contained four copper-binding conserved
      domains of typical laccase protein. The functionality of lac-En3-1 gene encoding
      active laccase was verified by expressing this gene in the yeast Pichia pastoris
      successfully. The recombinant laccase produced by the yeast transformant could
      decolorize the synthetic dyes, simulated dye effluents and the real textile dye
      effluent. The ability of decolorizing different dyes was positively related to
      the laccase activity. In addition, the 5'-flanking sequence upstream of the start
      codon ATG in lac-En3-1 gene was obtained. Many putative cis-acting responsive
      elements were predicted in the promoter region of lac-En3-1.

PMID- 21733625
TI  - Effect of humic acid on sorption of technetium by alumina.
AB  - Sorption of technetium by alumina has been studied in absence as well as in
      presence of humic acid using (95)Tc(m) as a tracer. Measurements were carried out
      at fixed ionic strength (0.1M NaClO(4)) under varying pH (3-10) as well as redox
      (aerobic and reducing anaerobic) conditions. Under aerobic conditions, negligible
      sorption of technetium was observed onto alumina both in absence and in presence
      of humic acid. However, under reducing conditions (simulated with [Sn(II)] = 10(
      6)M), presence of humic acid enhanced the sorption of technetium in the low pH
      region significantly and decreased at higher pH with respect to that in absence
      of humic acid. Linear additive as well as surface complexation modeling of Tc(IV)
      sorption in presence of humic acid indicated the predominant role of sorbed humic
      acid in deciding technetium sorption onto alumina.

PMID- 21733626
TI  - Taguchi optimization approach for Pb(II) and Hg(II) removal from aqueous
      solutions using modified mesoporous carbon.
AB  - Using the Taguchi method, this study presents a systematic optimization approach
      for removal of lead (Pb) and mercury (Hg) by a nanostructure, zinc oxide-modified
      mesoporous carbon CMK-3 denoted as Zn-OCMK-3. CMK-3 was synthesized by using SBA
      15 and then oxidized by nitric acid. The zinc oxide was loaded to the modified
      CMK-3 by the equilibrium adsorption of Zn(II) ions from aqueous solution followed
      by calcination to convert zinc nitrate to zinc oxide. The CMK-3 had porous
      structure and high specific surface area which can accommodate zinc oxide in a
      spreading manner, the zinc oxide connects to the carbon surface via oxygen atoms.
      The controllable factors such as agitation time, initial concentration,
      temperature, dose and pH of solution have been optimized. Under optimum
      conditions, the pollutant removal efficiency (PRE) was 97.25% for Pb(II) and 99%
      for Hg(II). The percentage contribution of each controllable factor was also
      determined. The initial concentration of pollutant is the most influential
      factor, and its value of percentage contribution is up to 31% and 43% for Pb and
      Hg, respectively. Our results show that the Zn-OCMK-3 is an effective
      nanoadsorbent for lead and mercury pollution remediation. Langmuir and Freundlich
      adsorption isotherms were used to model the equilibrium adsorption data for
      Pb(II) and Hg(II).

PMID- 21733627
TI  - Pomace waste management scenarios in Quebec--impact on greenhouse gas emissions.
AB  - Fruit processing industries generate tremendous amount of solid wastes which is
      almost 35-40% dry weight of the total produce used for the manufacturing of
      juices. These solid wastes, referred to as, "pomace" contain high moisture
      content (70-75%) and biodegradable organic load (high BOD and COD values) so that
      their management is an important issue. During the management of these pomace
      wastes by different strategies comprising incineration, landfill, composting,
      solid-state fermentation to produce high-value enzymes and animal feed, there is
      production of greenhouse gases (GHG) which must be taken into account. In this
      perspective, this study is unique that discusses the GHG emission analysis of
      agro-industrial waste management strategies, especially apple pomace waste
      management and repercussions of value-addition of these wastes in terms of their
      sustainability using life cycle assessment (LCA) model. The results of the
      analysis indicated that, among all the apple pomace management sub-models for a
      functional unit, solid-state fermentation to produce enzymes was the most
      effective method for reducing GHG emissions (906.81 tons CO(2) eq. per year),
      while apple pomace landfill resulted in higher GHG emissions (1841.00 tons CO(2)
      eq. per year). The assessment and inventory of GHG emissions during solid-state
      fermentation gave positive indications of environmental sustainability for the
      use of this strategy to manage apple pomace and other agricultural wastes,
      particularly in Quebec and also extended to other countries. The analysis and use
      of parameters in this study were drawn from various analytical approaches and
      data sources. There was absence of some data in the literature which led to
      consideration of some assumptions in order to calculate GHG emissions. Hence,
      supplementary experimental studies will be very important to calculate the GHG
      emissions coefficients during agro-industrial waste management.

PMID- 21733628
TI  - Pain in children--a call for more longitudinal research.

PMID- 21733629
TI  - Treatment of antecubital defect with infection and artery exposure.

PMID- 21733630
TI  - Another important factor affecting fluid requirement after severe burn: a
      retrospective study of 166 burn patients in Shanghai.
AB  - BACKGROUND: The modified Evans formula is the most often used schema for
      calculating intravenous resuscitation fluid requirement in burn patients in
      China, including two parameters: body weight and burnt body surface area (BBS).
      The aim of this retrospective study was to analyse depth of wound influencing
      intravenous fluid replacement in addition to these two factors. METHODS: We
      reviewed the records of 166 patients admitted in Shanghai Ruijin Hospital during
      2000-2008 whose BBS was larger than 25% total body surface area (TBSA). The
      modified Evans formula was used in all patients. The volume of fluid therapy was
      determined by urinary output. RESULT: In the first and second 24 h the volume of
      intravenous fluid resuscitation per bodyweight per BBS (VIWB) showed a
      significant positive correlation to full-thickness burn size ratio (FBSR: full
      thickness BBS/total BBS) (R(2)=0.138, P<0.001; R(2)=0.108, P<0.001). The volume
      of fluid resuscitation was not different than the modified Evans formula in
      superficial burn only patients. Each 20% increase in full-thickness burn size
      ratio increased 0.1 in volume infused per bodyweight per BBS in the first 24 h
      afterburn and 0.06 in the second 24 h. CONCLUSION: Full-thickness burn wounds
      received more volume of intravenous fluid than superficial burn wounds,
      especially in the second 24 h afterburn. The formula meets the fluid predictions
      of different depth of wound by using the modified fluid coefficients.

PMID- 21733631
TI  - Life goals and alcohol use among first-year college students: the role of motives
      to limit drinking.
AB  - The main objective of the present study was to advance our understanding of how
      life goals are associated with hazardous alcohol use among first-year university
      students. One-hundred and seventeen students rated a series of self-generated
      life goals on meaning and efficacy and then completed alcohol assessments. Higher
      goal meaning ratings were associated with less alcohol use and fewer heavy
      drinking episodes. Tests of indirect effects showed that the associations between
      goal meaning ratings and alcohol use indices were mediated by motives to limit
      drinking, particularly the motive to maintain self-control/standards. These
      results replicate and extend previous work on goal meaning and hazardous drinking
      among students. Findings are consistent with the view that engagement in
      university life goals may serve as a protective factor against hazardous drinking
      among first-year students due to greater concern with the impact of drinking on
      their ability to attain goal standards.

PMID- 21733632
TI  - Driving kids to smoke? Children's reported exposure to smoke in cars and early
      smoking initiation.
AB  - The health risks associated with second hand smoke (SHS) are well-known. However,
      little is known about exposure to SHS in cars and risk of smoking uptake. This
      paper investigates the association between pre-adolescents reported exposure to
      smoking in cars and prevalence of early stage smoking activity. Data from Keeping
      Kids Smokefree baseline surveys of students were used to investigate smoking
      status and reported exposure to smoking in cars. Log binomial regression analyses
      were used to investigate if reported exposure to SHS in cars was associated with
      smoking prevalence. 83% of 5676 students invited took part. After controlling for
      all variables reported exposure to smoking in cars and homes were significantly
      associated with increased risk of initiated smoking (RR 1.87, 95% CI 1.43-2.44,
      and RR 1.5, 95% CI 1.13-1.97, respectively). Exposure to smoking in cars was
      substantially and significantly associated with risk of current smoking (RR 3.21,
      95% CI 1.45-7.08). Early smoking uptake is associated with students' reported
      exposure to smoking in cars which confirms the importance of protecting children
      from SHS. Smoking in cars is under parental control and therefore modifiable.
      Moreover, children's reports of SHlS exposure offer a simple way of identifying
      families who can be targeted for tobacco control interventions.

PMID- 21733633
TI  - Tizanidine for alcohol withdrawal treatment.
AB  - The noradrenergic system is an important neurotransmission system implicated in
      the occurrence of alcohol withdrawal symptoms and anxiety leading to relapse
      during abstinence from alcohol usage. Tizanidine can play a role in alcohol
      withdrawal since it interferes with the noradrenergic system neurotransmission.
      Many noradrenergic system inhibitors in the central nervous system have proven
      their efficacy in the treatment of alcohol withdrawal syndrome. Imidazoline
      receptors have been also implicated in the pathophysiology of addiction.
      Tizanidine is an alpha2-adrenoreceptor agonist that inhibits noradrenaline
      release and binds to imidazoline receptors. It is used as an antispastic agent
      due to its central action on noradrenergic system. Although Tizanidine has been
      tested as a treatment for opioid withdrawal it has not been tried in alcohol
      withdrawal yet. A theoretical rationale supports the fact that it can be an
      efficient treatment for the alcohol withdrawal syndrome as well as for the
      prevention of relapses.

PMID- 21733634
TI  - TRPV1: a useful therapeutic target for patients with vulnerable coronary plaques.
AB  - Acute coronary syndromes are generally caused by atherosclerotic plaque rupture.
      Inflammation is one of the most important features of vulnerable plaque.
      Adventitial vanilloid receptor TRPV1 and sensory C-fibers may play a pistol role
      for adventitial inflammation. TRPV1 is also present in platelets, and the
      presence of this receptor may provide a link between inflammatory mediators and
      platelet activation in atherosclerosis. The hypothesis we propose here is that
      TRPV1 may be a useful therapeutic target for patients with vulnerable coronary
      plaques. The fact that statins act directly on sensory neurons to decrease
      expression of proinflammatory neuropeptides, supports our hypothesis as above.
      However, the mechanisms mediating this potential effect are poorly understood.
      Future studies are required to determine whether downregulated expression of
      TRPV1 contributes to these therapeutic actions.

PMID- 21733635
TI  - A note on the frequency of gastric ulcers detected during post-mortem examination
      at a pig abattoir.
AB  - There is growing interest in using findings from post-mortem meat inspection as
      indicators of on-farm and preslaughter animal welfare. This study considered
      whether oesophago-gastric ulcers might be a useful feature in pigs. The stomachs
      of 9827 finishing pigs from 60 farms were examined to provide an estimate of the
      frequency of oesophago-gastric ulcers in England. Stomachs were graded using a
      four-point scale ranging from normal, hyperkeratotic, eroded or ulcerated with or
      without stenosis. Over 79% of stomachs had either an oesophago-gastric ulcer or
      visible pre-ulcerative changes, including hyperkeratosis of the epithelium lining
      the pars oesophagea. The frequency of severe ulceration (Grade 3) was 6%, and
      mild ulcers (Grades 1 and 2) 73%. There was a significantly higher frequency of
      oesophago-gastric lesions in the groups of pigs that were held at the abattoir
      overnight, compared with those slaughtered on the day of arrival. This could have
      been due to the combined effect of overnight fasting plus stress in an unfamiliar
      environment. However, the exact fasting times of the animals were unknown and so
      it was not possible to provide a precise assessment of the effect of feed
      withdrawal.

PMID- 21733636
TI  - [Inflammatory bowel diseases: gynecological and obstetrical considerations].
AB  - Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative
      colitis, are invalidating inflammatory affections, which evolve by relapse
      interrupted with clinical remission. Crohn's disease commonly affects young women
      in their reproductive years with a peak of incidence between 20 and 30.
      Infertility and sexual dysfunction are equivalent to that of the general
      population while they are increasing in patients with active IBD or after
      colorectal surgery. IBD are well controlled by medical treatments and the
      frequency of relapse during the pregnancy is similar to that of the non-pregnant
      IBD patients. The data concerning the risk of congenital malformations in IBD are
      contradictory. The risk of preterm delivery and low birth weight is significantly
      increased and correlated to the disease activity. When a medical treatment
      insures a quiescent disease before the pregnancy, it is advisable to continue it
      during the pregnancy because the benefits of controlled disease outweigh the
      risks of medication. IBD, possible perianal lesions and colorectal surgical
      interventions influence the mode of delivery, but the indication of caesarean
      section should primarily be governed by obstetric necessity. Preconceptional
      counseling seems desirable because of the risks during pregnancy, according to
      the disease activity, the surgical histories and the therapeutic agents.

PMID- 21733637
TI  - [Collodion baby and respiratory distress syndrome].
AB  - The congenital ichthyosis appears mainly in the form of collodion baby. This one
      can be suspected in case of polyhydramnios associated with a snowy aspect of the
      amniotic liquid in the antenatal echography. The reported four cases of collodion
      baby were premature children having presented a respiratory distress syndrome of
      variable gravity. The pulmonary disease was of multifactorial origin. The outcome
      was favorable for four children.

PMID- 21733638
TI  - [Anti-TNFalpha therapy and its implication in gynecology and obstetrics].
AB  - Anti-TNFalpha treatments have modified the medical care, the course and the
      quality of life of the patients with autoimmune rheumatic, cutaneous or bowel
      inflammatory diseases. On the other hand, these treatments may have potential
      severe side effects during pregnancy (congenital malformations, fetal
      infections). Actually, many pregnancies have been reported during anti-TNFalpha
      exposures, with good maternal and neonatal outcomes. The introduction or the
      discontinuation of these treatments will always have to be discussed with the
      specialist of the chronic disease and, ideally, during a preconceptional
      counselling. In gynecology, anti-TNFalpha drugs may offer a new safe and
      effective approach to treating patients with recurrent miscarriages or
      unexplained or failed in vitro fertilization cycles. On the other hand, these
      treatments significantly increase the risk for serious infections or viral
      reactivations and may promote gynaecological malignancies. An adapted
      gynaecological survey is necessary.

PMID- 21733639
TI  - [Value of fetal scalp pH sampling early during the first stage of labour].
AB  - OBJECTIVE: When fetal heart rate (FHR) abnormalities occur early during the first
      stage of labour, the risk of caesarean increases. In this study, we assessed the
      value of fetal scalp pH sampling on delivery mode, among women with FHR
      abnormalities before or at 5 cm cervical dilatation. METHODS: It is a
      retrospective observational study setting in a tertiary maternity center. All
      women with a live singleton cephalic fetus at term, who had a fetal scalp pH
      sampling, between January and July 2009, were included. We compared vaginal
      delivery and neonatal morbidity rates according to cervical dilatation at the
      time of the first fetal scalp pH sampling (<= 5 or >5 cm). Neonatal morbidity was
      defined by pH at birth less or equal to 7.10 and/or 5 minutes Apgar score less or
      equal to 7 and/or neonatal transfer. RESULTS: During the study period, 108 women
      had at least one fetal scalp pH sampling, 8.5% of eligible women. Forty-six
      (42.6%) had a first pH at or before 5 cm cervical dilatation. The vaginal
      delivery rate was 62% and increased with increasing cervical dilatation at the
      time of the first fetal scalp pH (P<0.001). Among women who had fetal scalp pH
      early during the first stage of labour (<= 5 cm), 50% delivered vaginally versus
      71% when the fetal scalp pH was performed after 5 cm (P=0.026). The frequency of
      pH at birth less or equal to 7.10 was lower when the fetal scalp pH was performed
      before or at 5 cm (4.4% versus 16.9%, P=0.04). Neonatal morbidity rates were
      similar in both groups. CONCLUSION: In this study, when FHR abnormalities occur
      early during the first stage of labour, use of fetal scalp pH sampling allows a
      vaginal delivery in half of cases without an increase in neonatal morbidity.

PMID- 21733640
TI  - [Detection of Staphylococcus aureus resistant to methicillin (MRSA) by molecular
      biology (Cepheid GeneXpert IL, GeneOhm BD, Roche LightCycler, Hyplex Evigene I2A)
      versus screening by culture: Economic and practical strategy for the laboratory].
AB  - OBJECTIVES: Patients admitted in cardiac surgery and cardiac ICU at the Clinic
      Saint-Gatien (Tours) are screened for MRSA at the entrance by nasal swab and
      culture on blood agar and selective chromogenic medium made by addition of
      cefoxitin: BBL CHROMagar MRSA-II BD (result obtained at Day +1). We wanted to
      assess the molecular biology techniques available to obtain a result at day 0 for
      the majority of patients and to define an economic and practical strategy for the
      laboratory. TECHNIQUES: We studied four molecular biology techniques: Cepheid
      GeneXpert (Cepheid) GeneOhm (BD), LightCycler (Roche) and Hyplex (I2A). Upon
      reception, nasal swabs were treated by culture, considered as reference, and one
      of the techniques of molecular biology, according to the manufacturer's notice.
      We conducted four studies between April 2008 and February 2009 to obtain a
      significant sample for each of them. METHODS: By screening we mean a method that
      allows us to exclude MRSA carriage for patients waiting for surgery, and not to
      change patient management: for example, lack of isolation measures specific to
      entrance, no modification of antibiotic prophylaxis during surgery and no
      isolation measures in the immediate postoperative period. RESULTS: The criteria
      we considered for this evaluation were: (1) technician time: time to perform one
      or a series of sample(s) n=10 or more (about 2h for all techniques except
      GeneXpert 75min), level of skilled competences (no specific training for
      GeneXpert); (2) results: turnaround time (all molecular biology techniques), ease
      of reading and results interpretations (no specialized training required for
      GeneXpert), failure or not (12% of failure of internal controls for GeneOhm); (3)
      economic: cost for one or a series of sample(s) (n=10 or more), if we considered
      X as the reference culture cost (10 X Hyplex and LightCycler, 20 X and 40 X for
      GeneXpert GeneOhm); (4) NPV: 100% for GeneXpert and LightCycler. CONCLUSION: At
      same sensitivity, no technique, including culture, can solve alone our problem,
      which is: (1) get results at day 0 for batch of samples (n<10): all molecular
      biology techniques; (2) beyond 10 samples: LightCycler (Roche) automated or
      Hyplex (I2A) manual; (3) when the result at day 1 is sufficient, the use of
      chromogenic agar with a reading of less than 18h as BBL CHROMagar MRSA II (BD)
      remains the most economical; (4) to be sure that a patient admitted at Day 0,
      even at night's emergency, is not carrier of MRSA: only Cepheid GeneXpert
      technology (IL). Furthermore, Cepheid GeneXpert (IL) allows performing several
      tests in parallel. The rapidity of this system can help control the transmission
      and make better use of antibiotics.

PMID- 21733641
TI  - [Celiac disease.]

PMID- 21733642
TI  - Ability of baclofen to prevent somatic manifestations and neurochemical changes
      during nicotine withdrawal.
AB  - BACKGROUND: Nicotine (NIC), the major active component of tobacco, is critical in
      the maintenance of the smoking habit. The aims of the present study were to
      analyze the behavioural and neurochemical variations during NIC withdrawal
      syndrome in mice, and whether they are prevented with baclofen (BAC, GABA(B)
      receptor agonist). METHODS: Swiss-Webster albino mice received NIC (2.5 mg/kg,
      s.c.) 4 times daily, for 7 consecutive days. On day 8 (the day of the
      experiment), NIC-treated mice received the nicotine antagonist mecamylamine (MEC,
      2 mg/kg, i.p.) 1h after the last dose of NIC. A second group of dependent mice
      received BAC (2mg/kg, i.p.) before MEC-precipitated abstinence. The somatic signs
      were measured for 30 min. Dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT)
      and its metabolites concentrations were determined by HPLC in the striatum,
      cortex and hippocampus. RESULTS: The global score was greater in the abstinent
      group compared to the control group. Moreover, the global score time course
      showed a higher increase at 10 min compared to the global score at 5 min or 30
      min after MEC-precipitated NIC withdrawal. In addition, the global score was
      attenuated by BAC. The DA and dihydroxyphenyl acetic acid (DOPAC) cortical levels
      decreased in the abstinent group, while BAC reestablished these levels 10 min
      after NIC withdrawal. Furthermore, DA and 5-HT striatal levels decreased during
      NIC withdrawal, and BAC reverted this decrease. CONCLUSION: In conclusion, the
      prevention of NIC withdrawal signs by BAC could be related to changes in
      dopaminergic and serotonergic activity.

PMID- 21733643
TI  - Antimicrobial susceptibility pattern of Helicobacter suis strains.
AB  - Helicobacter suis is a very fastidious porcine gastric pathogen, which is also
      considered to be of zoonotic importance. In vitro antimicrobial susceptibility
      cannot be determined using standard assays, as this agent only grows in a
      biphasic medium with an acidic pH. Therefore, a combined agar and broth dilution
      method was used to analyse the activity of nine antimicrobial agents against nine
      H. suis isolates. After 48 h microaerobic incubation, minimal inhibitory
      concentrations (MICs) were determined by software-assisted calculation of
      bacterial growth. Only for enrofloxacin a bimodal distribution of MICs was
      demonstrated, indicating acquired resistance in one strain, which showed an AGT
      >AGG (Ser->Arg) substitution at codon 99 of gyrA. In conclusion, the assay
      developed here is suitable for determination of the antimicrobial susceptibility
      of H. suis isolates, although activity of acid sensitive antimicrobial agents may
      be higher than predicted from MIC endpoints.

PMID- 21733644
TI  - Molecular characterization of Corynebacterium pseudotuberculosis isolates using
      ERIC-PCR.
AB  - Caseous lymphadenitis is an infectious sheep and goats disease caused by
      Corynebacterium pseudotuberculosis and characterized by abscesses in superficial
      and visceral lymph nodes. C. pseudotuberculosis strains isolated from these hosts
      have been shown to be very difficult to type by the existing methods. The aim of
      this study is evaluating the potential of the Enterobacterial Repetitive
      Intergenic Consensus (ERIC-PCR) as a tool for molecular typing of C.
      pseudotuberculosis strains isolated in sheep. One hundred and twenty seven
      isolates of C. pseudotuberculosis were isolated from lesions suspected to have
      had caseous lymphadenitis collected from sheep at the slaughterhouse. Animals
      were from 24 flocks in 13 municipalities of the Minas Gerais State, Brazil.
      Species identification of the isolates was performed by routine biochemical tests
      and mPCR. Fingerprint was performed by RAPD using ERIC-1R, ERIC-2 and ERIC
      1R+ERIC-2 primers. Seventeen different genotypes were generated by ERIC 1-PCR, 21
      genotypes by ERIC 2-PCR and 21 genotypes by ERIC 1+2-PCR. Hunter-Gaston
      Discrimination Index (HGDI) found for ERIC 1, ERIC 2, ERIC 1+2 PCR were 0.69,
      0.87, and 0.84, respectively. For most herds evaluated observed at most three
      different genotypes among isolates from animals of these property, in all ERIC
      PCR assays. However a few flocks observed between four and nine genotypes per
      flock. The W Kendall value found for correlation among the three techniques of
      ERIC-PCR was 0.91 (P<5.0 x 10(-6)). The results show that ERIC-PCR has good
      discriminatory power and advantages over other DNA-based typing methods, making
      it a useful tool to discriminate C. pseudotuberculosis isolates.

PMID- 21733645
TI  - Thymosin beta 10 expression in developing human salivary glands.
AB  - Thymosin beta 10 (Tbeta10) is a member of beta-thymosins (Tbetas), a family of
      low molecular mass peptides abundant in many cell types. In previous studies,
      Tbetas have been shown to play essential roles in many cellular functions,
      including cytokinesis, migration and endocytosis. Recently, Tbeta10 has been
      found in high quantities in the saliva of human newborns, while it disappeared in
      the adults. On the basis of these data, it seemed of some interest to study the
      influence of Tbeta10 during the development of the human salivary glands. To this
      end, we analyzed, using immunocytochemistry, the expression of Tbeta10 in samples
      of the major and minor salivary glands obtained, at autopsy, from 2 human fetuses
      and 4 newborns, ranging from 13 up to 33weeks of gestation. Tbeta10
      immunoreactivity was detected in all salivary glands examined, with marked
      differences from one gland to the next, the parotid glands showing the highest
      Tbeta10 reactivity and minor salivary glands the lowest reactivity. Marked
      changes were observed in Tbeta10 expression and localization during
      embryogenesis. Tbeta10 was mainly localized extracellularly in the youngest human
      fetuses (13weeks), in the cytoplasm of immature duct cells at 20weeks, in acinar
      cells and in the duct lumen in 33weeks old fetuses. Our data show, for the first
      time, a strong expression of Tbeta10 in the human salivary glands during the
      initial phases of the physiological development, present at the 13th week of
      gestation, and suggesting a role for the peptide in the salivary glands'
      organogenesis.

PMID- 21733646
TI  - Internal artificial vagina (IAV) to assess breeding behavior of young Bos taurus
      and Bos indicus bulls.
AB  - Bull breeding soundness evaluation (BBSE) usually neglects the libido and mating
      ability evaluation. The internal artificial vagina (IAV) permits semen sampling,
      as well as mating ability evaluation. Few studies have been performed using IAV
      with young bulls and there are none with Bos indicus bulls. The present study
      evaluated sexual behavior, mating ability and semen quality in young Bos taurus
      (Devon) and B. indicus (Nellore) bulls using the IAV device. In the first
      experiment, 52 Devon bulls, 18-25 months old were observed, and the behavior and
      mating ability recorded over a 10-min period within a restrained mount-cow with
      an IAV inserted. In the second experiment, 20 Nellore bulls, 20-30 months old
      were evaluated over a 20 min period. Of the 52 Devon bulls, 45 (86.5%) had semen
      recovered with the IAV, 31 (69.0%) were considered satisfactory. Nellore bulls
      exhibited a different sexual behavior, with 10 bulls not showing any interest in
      the females. Four bulls demonstrated sexual interest only once, e.g., sniffing,
      two showed interest on more than one occasion, and four had more than two mounts
      or mounting attempts. None out of the Nellore bulls was collected with IAV. The
      IAV was an effective and welfare-promoting animal technology for the evaluation
      of semen quality and mating ability of B. taurus bulls. However, the IAV was not
      adequate for young Nellore bulls, probably due to their quiescent sexual behavior
      and delayed sexual maturity. Further studies are needed to evaluate the
      performance of the IAV for older Nellore bulls.

PMID- 21733647
TI  - Vaginal DHEA to treat menopause related atrophy: a review of the evidence.
AB  - Vaginal atrophy is a common symptom of postmenopausal estrogen deficiency and can
      present as dryness, irritation, infection and dyspareunia and can affect sexual
      function and quality of life. Currently vaginal atrophy is treated with the
      intravaginal application of preparations containing estradiol or estriol, which
      are both effective and safe. It has been proposed that intravaginally
      administered dehydroepiandrosterone (DHEA) can be used to treat vaginal atrophy.
      DHEA and its sulphate DHEAS are the most abundant circulating sex steroid
      hormones in women, and provide a large precursor reservoir for the intracellular
      production of androgens and estrogens in non-reproductive tissues. Levels of DHEA
      and DHEAS decline with age. Although there is some evidence to support the use of
      intravaginal DHEA for postmenopausal women with symptoms of vaginal atrophy,
      independent studies are required to confirm this. In addition studies regarding
      the effects of vaginal DHEA on sexual function in women without vaginal atrophy
      are needed. Given that the efficacy and long term safety of low dose vaginal
      estradiol and estriol therapy is well established and that vaginal estrogen
      requires application of 2-3 times a week, rather than daily dosing; the benefit
      of daily vaginal DHEA over estrogen also needs to be considered as women may find
      it unpalatable to adhere to daily dosing with a cream preparation.

PMID- 21733648
TI  - Dynamic liveness and forgeries detection of the finger surface on the basis of
      spectroscopy in the 400-1650 nm region.
AB  - Differentiation of living fingers, fake fingers and fingers from dead bodies was
      investigated using spectral analysis. For this purpose, reflection and
      transmission spectra in the wavelength region from 400 to 1650 nm were recorded
      from living volunteers and corpses. In an additional small test series (one
      living volunteer, three cadavers), time-resolved spectral images were prepared
      using reflectance (derived from pulse oximetry). The dynamic differences in the
      curves (including the absorption changes caused by the blanching effect and the
      pulse) provide initial approaches for the realisation of systems for liveness
      detection. Significant differences that would be useful for the integration into
      fingerprint recording systems of methods to defend against forgeries are
      discussed.

PMID- 21733649
TI  - Segmentation process significantly influences the accuracy of 3D surface models
      derived from cone beam computed tomography.
AB  - AIMS: To assess the accuracy of surface models derived from 3D cone beam computed
      tomography (CBCT) with two different segmentation protocols. MATERIALS AND
      METHODS: Seven fresh-frozen cadaver heads were used. There was no conflict of
      interests in this study. CBCT scans were made of the heads and 3D surface models
      were created of the mandible using two different segmentation protocols. The one
      series of 3D models was segmented by a commercial software company, while the
      other series was done by an experienced 3D clinician. The heads were then
      macerated following a standard process. A high resolution laser surface scanner
      was used to make a 3D model of the macerated mandibles, which acted as the
      reference 3D model or "gold standard". The 3D models generated from the two
      rendering protocols were compared with the "gold standard" using a point-based
      rigid registration algorithm to superimpose the three 3D models. The linear
      difference at 25 anatomic and cephalometric landmarks between the laser surface
      scan and the 3D models generate from the two rendering protocols was measured
      repeatedly in two sessions with one week interval. RESULTS: The agreement between
      the repeated measurement was excellent (ICC=0.923-1.000). The mean deviation from
      the gold standard by the 3D models generated from the CS group was 0.330mm+/
      0.427, while the mean deviation from the Clinician's rendering was 0.763mm+/
      0.392. The surface models segmented by both CS and DS protocols tend to be larger
      than those of the reference models. In the DS group, the biggest mean differences
      with the LSS models were found at the points ConLatR (CI: 0.83-1.23), ConMedR
      (CI: -3.16 to 2.25), CoLatL (CI: -0.68 to 2.23), Spine (CI: 1.19-2.28), ConAntL
      (CI: 0.84-1.69), ConSupR (CI: -1.12 to 1.47) and RetMolR (CI: 0.84-1.80).
      CONCLUSION: The Commercially segmented models resembled the reality more closely
      than the Doctor's segmented models. If 3D models are needed for surgical drilling
      guides or surgical planning which requires high precision, the additional cost of
      the commercial segmentation services seem to be justified to produce a more
      accurate surface models.

PMID- 21733650
TI  - Primarily solid intraventricular brain tumors.
AB  - Solid intraventricular-neoplasms are readily seen on cross-sectional images, but
      the myriad of entities to be considered may make a focused differential diagnosis
      elusive. Clinical symptoms of patients with intraventricular-tumors are non
      specific and are generally related to increased intracranial pressure or
      hydrocephalus. The objective of this article is to present the most relevant
      demographic, clinical and imaging features of solid intraventricular-tumors for
      the purpose of a more comprehensive differential-diagnosis.

PMID- 21733651
TI  - Complications and co-morbidities in radiographs of patients in traditional bone
      setters' homes in Ogwa, Edo State, Nigeria: a community-based study.
AB  - BACKGROUND: Musculoskeletal injuries are common in developing countries, but
      access to high quality orthopedic care is not. Traditional bone setters (TBS)
      serve to fill the gap, but the nature and quality of their treatment are largely
      understudied. Traditional bone setting in Idunmunkpaghan clan of Ogwa community,
      Edo State, Nigeria, was founded by Odion Ekhimere between about 1680 and 1705.
      The TBS practice in this community is studied to find out the complications and
      co-morbidities associated with it. METHODS: A prospective community-based study
      of the patients admitted in the traditional bone setters' homes was done at Ogwa
      over a -2-year period by studying the admission and discharge radiographs of
      patients treated in the community and by interviewing the TBS and patients.
      RESULT: Ninety patients with radiographs of the lesion sites were followed up
      from admission to discharge at the TBS homes, comprising 53 males (53.89%) and 37
      females (41.11%) with a male to female ratio of 1.4:1. Sixty five patients
      (72.2%) had fracture or dislocation. Forty four of the 65 patients (67.7%) with
      fracture/dislocation had complications including mal-union 31(70.4%), secondary
      osteoarthritis 8 (18.2%), non-reduction of dislocation 7 (11.9%), non-union 8
      (18.2%), and others 12 (27.2%). Co-morbidities were identified in 15 patients
      (16.7%) and included severe osteoarthritis 7 (46.7%), diabetic foot ulcer 4
      (26.7%), severe hypertension with cardiomegaly 4 (26.7%), metastatic carcinoma of
      the prostate 3 (20.0%), septic arthritis 2 (13.3%), pulmonary tuberculosis 1
      (6.7%) and others 3 (20.0%). CONCLUSION: The practice of traditional bone setting
      is well established in Idunmunkpaghan clan in Ukpogo quarter of Ogwa. Education
      and training of the TBS is the key to reduction of complications and co
      morbidities seen in their practices as they have high patronage and the patients
      have high regards for them and will continue to patronize them.

PMID- 21733652
TI  - Simultaneous quantification of 17 constituents from Yuanhu Zhitong tablet using
      rapid resolution liquid chromatography coupled with a triple quadrupole
      electrospray tandem mass spectrometry.
AB  - A rapid resolution liquid chromatography coupled with a triple quadrupole mass
      spectrometry (RRLC-QQQ) was employed to identify and quantify the major bioactive
      constituents in Yuanhu Zhitong tablet (YZT), a traditional Chinese medicine.
      Seventeen constituents were simultaneously determined and quantified by reference
      standards in 9 min, namely scopoletin, protopine, alpha-allocryptopine,
      tetrahydropalmatine, coptisine, tetrahydroberberine, corydaline, berberine,
      byakangelicin, byakangelicol, xanthotoxin, bergapten, pimpinellin, oxypeucedanin,
      imperatorin, osthole and isoimperatorin. All of them were performed on an Agilent
      XDB C(18) column (4.6 mm * 50 mm, 1.8 MUm) with linear gradient elution of
      acetonitrile-0.3% formic acid water (pH 2.7). The proposed method was applied to
      analyze 15 batches of samples with acceptable linearity (r(2), 0.9938-0.9999),
      precisions (RSD, 1.01-4.92%), repeatability (RSD, 1.33-4.91%), stability (RSD,
      1.46-4.86%), recovery (RSD, 1.11-4.81%) of the seventeen compounds. Furthermore,
      the Hierarchical Cluster Analysis was applied to classify 15 samples based on
      characteristics of the 17 compound markers. As a result, the analytical method
      possessing high sensitivity and speed is suitable for the quality control of YZT.

PMID- 21733653
TI  - Assessing patient-centered communication in a family practice setting: how do we
      measure it, and whose opinion matters?
AB  - OBJECTIVE: This study evaluated variables thought to influence patient's
      perceptions of patient-centeredness. We also compared results from two coding
      schemes that purport to evaluate patient-centeredness, the Measure of Patient
      Centered Communication (MPCC) and the 4 Habits Coding Scheme (4HCS). METHODS: 174
      videotaped family practice office visits, and patient self-report measures were
      analyzed. RESULTS: Patient factors contributing to positive perceptions of
      patient-centeredness were successful negotiation of decision-making roles and
      lower post-visit uncertainty. MPCC coding found visits were on average 59%
      patient-centered (range 12-85%). 4HCS coding showed an average of 83 points
      (maximum possible 115). However, patients felt their visits were highly patient
      centered (mean 3.7, range 1.9-4; maximum possible 4). There was a weak
      correlation between coding schemes, but no association between coding results and
      patient variables (number of pre-visit concerns, attainment of desired decision
      making role, post-visit uncertainty, patients' perception of patient
      centeredness). CONCLUSIONS: Coder inter-rater reliability was lower than
      expected; convergent and divergent validity were not supported. The 4HCS and MPCC
      operationalize patient-centeredness differently, illustrating a lack of
      conceptual clarity. PRACTICE IMPLICATIONS: The patient's perspective is
      important. Family practice providers can facilitate a more positive patient
      perception of patient-centeredness by addressing patient concerns to help reduce
      patient uncertainty, and by negotiating decision-making roles.

PMID- 21733654
TI  - Language, culture and emotions: exploring ethnic minority patients' emotional
      expressions in primary healthcare consultations.
AB  - OBJECTIVE: This study explores ethnic minority patients' expression of emotional
      cues and concerns in primary healthcare, and examines relationships with patient,
      provider and consultation attributes. METHODS: 191 video-recorded consultations
      were analyzed using the VR-CoDES. Patients were interviewed before the
      consultation. Generalized Estimating Equations models (GEE) were used to test for
      associations. RESULTS: Psychosocial versus bio-medically oriented encounters
      contained significantly more cues (p<=0.05). Patients with poor versus good
      language proficiency expressed significantly less cues (p<=0.001). No significant
      correlations were found with patients' cultural values, patients' or physicians'
      gender or the presence of an interpreter. Female patients express more concerns
      (p<=0.05), female physicians have a higher number of concerns expressed by
      patients (p<=0.02). CONCLUSION: This study shows that independent of physician
      and diagnosis, patients' language proficiency has a more important impact on the
      number of cues expressed by the patient than cultural difference. PRACTICE
      IMPLICATIONS: Medical schools and Continuing Medical Education should focus on
      training programs for recognizing and handling linguistic barriers between
      physicians and patients. Patient education programs should encourage patients who
      experience language barriers to open up to physicians. In situations where
      language is a barrier, physicians and patients should be encouraged to use
      interpreters to enhance the expression of emotions.

PMID- 21733655
TI  - CD147 overexpression allows an accurate discrimination of bladder cancer
      patients' prognosis.
AB  - BACKGROUND: Urothelial bladder carcinoma (UBC) is a chemo-sensitive tumour, but
      the response to treatment is heterogeneous. CD147 has been associated with
      chemotherapy resistance. We aimed to define tumours with an aggressive phenotype
      by the combined analysis of clinicopathological and biological parameters.
      METHODS: 77 patients with T1G3 or muscle-invasive UBC treated by radical
      cystectomy were studied. Immunohistochemistry was performed to detect CD147,
      heparanase, CD31 (blood vessels identification) and D2-40 (lymphatic vessels
      identification) expressions. The immunohistochemical reactions were correlated
      with the clinicopathological and the outcome parameters. 5-year disease-free
      survival (DFS) and overall survival (OS) rates were estimated using the Kaplan
      Meier method. Multivariate analysis was performed by Cox proportional hazards
      analysis. RESULTS: The 5-year DFS and OS rates were significantly influenced by
      the classical clinicopathological parameters, and by the occurrence of
      lymphovascular invasion. CD147 and heparanase immunoexpression did not affect
      patients' outcome. However, patients with pT3/pT4 tumours had a median OS time of
      14.7 months (95% CI 7.1-22.3, p = 0.003), which was reduced to 9.2 months (95% CI
      1.5-17.0, p = 0.008) if the tumours were CD147 positive. We developed a model of
      tumour aggressiveness using parameters as stage, grade, lymphovascular invasion
      and CD147 immunoexpression, which separated a low aggressiveness from a high
      aggressiveness group, remaining as an independent prognostic factor of DFS (HR
      3.746; 95% CI 1.244-11.285; p = 0.019) and OS (HR 3.247; 95% CI 1.015-10.388, p =
      0.047). CONCLUSION: CD147 overexpression, included in a model of UBC
      aggressiveness, may help surgeons to identify patients who could benefit from a
      personalized therapeutic regimen. Additional validation is needed.

PMID- 21733656
TI  - An experimental approach to studying the effectiveness and safety of meglumine
      antimoniate formulations.
AB  - Among the problems associated to leishmaniasis, the two most outstanding ones are
      the lack of a vaccine and the adverse effects caused by drugs use for its
      control. Meglumine antimoniate compounds are the first-line drugs in the
      treatment for cutaneous leishmaniasis (the most prevalent form of the disease in
      Colombia); nevertheless, they are far from being ideal drugs due to their
      toxicity (not to mention the emergence of drug-resistant parasites), all of which
      has prompted current search for new strategies to improve their safety. This work
      assesses the effectiveness and safety (toxicity including new aspects related
      with immunotoxicity not reported previously) of two different meglumine
      antimoniate formulations using an in vitro and in vivo murine model. The results
      evidence that although both injectable formulations induce an equally efficient
      (clearance of intracellular parasites), both give rise to adverse effects,
      including a preferential immunomodulation on Balb/c mice and in a lesser
      proportion on ICR mice. These results are comparable to human trials reporting
      variable reactions when following the same treatment regimen. The model presented
      herein is proposed as a tool for evaluating the effectiveness and safety of
      meglumine antimoniate-based antileishmanial formulations.

PMID- 21733657
TI  - Cardiac CT: practical approach to integrate appropriate indications in daily
      practice.
AB  - Recent advances in CT technologies had significantly improved the clinical
      utility of cardiac CT. Major efforts have been made to optimize the image
      quality, standardize protocols and limit the radiation exposure. Rapid progress
      in post-processing tools dedicated not only to the coronary artery assessment but
      also to the cardiac cavities, valves and veins extended applications of cardiac
      CT. This potential might be however used optimally considering the current
      appropriate indications for use as well as the current technical imitations.
      Coronary artery disease and related ischemic cardiomyopathy remain the major
      applications of cardiac CT and at the same time the most complex one. Integration
      of a specific knowledge is mandatory for optimal use in this area for
      asymptomatic as for symptomatic patients, with a specific regards to patient with
      acute chest pain. This review aimed to propose a practical approach to implement
      appropriate indications in our routine practice. Emerging indications and future
      direction are also discussed. Adequate preparation of the patient, training of
      physicians, and the multidisciplinary interaction between actors are the key of
      successful implementation of cardiac CT in daily practice.

PMID- 21733658
TI  - Pro-epileptic effects of the cannabinoid receptor antagonist SR141716 in a model
      of audiogenic epilepsy.
AB  - Endocannabinoid system and its CB1 receptors are suggested to provide endogeneous
      protection against seizures. The present study examines whether CB1 receptors
      contribute to resistance to seizures and kindling epileptogenesis in a model of
      audiogenic epilepsy. Three groups of Wistar rats were used: rats unsusceptible to
      audiogenic seizures, rats with acquired resistance to audiogenic seizures and
      rats with reproducible audiogenic running seizures. Chronic treatment with the
      CB1 receptor antagonist SR141716 (5 daily dosing of 30mg/kg) did not change
      innate resistance to audiogenic seizures in non-epileptic rats but reverted
      acquired seizure resistance in rats which lost their epileptic sensitivity with
      repeated testing. In the latter rats, audiogenic running seizures reappeared for
      at least two weeks after the end of treatment. In rats with reproducible seizure
      response, acutely, SR lengthened audiogenic seizures due to prolongation or
      appearance, de novo, of post-running limbic clonus without any effect on running
      seizure per se. This limbic component mimicked audiogenic kindling and indicated
      propagation of sound-induced brainstem seizure to the limbic forebrain. After
      chronic SR administration the incidence of the limbic clonus remained to be
      increased for at least two weeks. The present study supports the hypothesis about
      a role of CB1 receptors in endogeneous anticonvulsive mechanisms of the brain.

PMID- 21733659
TI  - Seizure susceptibility in polymicrogyria: clinical and experimental approaches.
AB  - Polymicrogyria is a cerebral cortical malformation characterized by an
      excessively folded cortical ribbon of miniature and individually thin
      convolutions. Although polymicrogyria is a highly epileptogenic lesion, its
      epileptogenic mechanism is unclear. The anomalous cortex associated with
      polymicrogyria includes less excitable neural tissue such as a cell sparse zone,
      but involves a part of a larger epileptic network extending to adjacent cortical
      areas. This malformation can be modeled in rats with a transcortical prenatal or
      neonatal freeze lesion, which mimics the histological characteristics of a human
      four-layered polymicrogyria. Several hypotheses have so far been presented for
      seizure susceptibility in polymicrogyria, including alterations of glutamate
      receptor distribution, abnormalities in ion channels, new excitatory or
      inhibitory connections, and downregulation of GABA(A) receptor subunits. The
      cortical hyperexcitability in polymicrogyria may be reduced by the inhibitory
      neuronal network. Further detailed investigations of a population with aberrantly
      migrating inhibitory interneurons will provide novel and important insights into
      the pathogenetic mechanisms of epilepsy in polymicrogyria.

PMID- 21733660
TI  - European ancestry and polymorphisms in DNA repair genes modify the risk of
      melanoma: a case-control study in a high UV index region in Brazil.
AB  - BACKGROUND: UV radiation is the major environmental factor related to development
      of cutaneous melanoma. Besides sun exposure and the influence of latitude, some
      host characteristics such as skin phototype and hair and eye color are also risk
      factors for melanoma. Polymorphisms in DNA repair genes could be good candidates
      for susceptibility genes, mainly in geographical regions exposed to high solar
      radiation. OBJECTIVE: Evaluate the role of host characteristics and DNA repair
      polymorphism in melanoma risk in Brazil. METHODS: We carried out a hospital-based
      case-control study in Brazil to evaluate the contribution of host factors and
      polymorphisms in DNA repair to melanoma risk. A total of 412 patients (202 with
      melanoma and 210 controls) were analyzed regarding host characteristics for
      melanoma risk as well as for 11 polymorphisms in DNA repair genes. RESULTS: We
      found an association of host characteristics with melanoma development, such as
      eye and hair color, fair skin, history of pigmented lesions removed, sunburns in
      childhood and adolescence, and also European ancestry. Regarding DNA repair gene
      polymorphisms, we found protection for the XPG 1104 His/His genotype (OR 0.32;
      95% CI 0.13-0.75), and increased risk for three polymorphisms in the XPC gene
      (PAT+; IV-6A and 939Gln), which represent a haplotype for XPC. Melanoma risk was
      higher in individuals carrying the complete XPC haplotype than each individual
      polymorphism (OR 3.64; 95% CI 1.77-7.48). CONCLUSIONS: Our data indicate that the
      host factors European ancestry and XPC polymorphisms contributed to melanoma risk
      in a region exposed to high sun radiation.

PMID- 21733661
TI  - Pragmatic management of Panton-Valentine leukocidin-associated staphylococcal
      diseases.
AB  - Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus is associated
      with a broad spectrum of diseases, ranging from common uncomplicated soft tissue
      infections to severe diseases such as complicated soft tissue infections,
      extensive bone and joint infections, and necrotising pneumonia. Specialised
      management of infection based on the presence of PVL may not be required for mild
      infections, whereas it could be lifesaving in other settings. Moreover, most
      severe PVL diseases are recently identified entities and a 'gold standard'
      treatment from comparatives studies of different therapeutic options is lacking.
      Thus, recommendations are based on expert opinions, which are elaborated based on
      theory, in vitro data and analogies with other toxin-mediated diseases. In this
      review, we consider the potential need for specialised PVL-based management and,
      if required, which tools should be used to achieve optimal management.

PMID- 21733662
TI  - Will new generations of modified antimicrobial peptides improve their potential
      as pharmaceuticals?
AB  - The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly
      established in the literature, and most research articles on this topic conclude
      by stating that AMPs represent promising therapeutic agents against bacterial and
      fungal pathogens. Indeed, early research in this field showed that AMPs were
      diverse in nature, had high activities with low minimal inhibitory
      concentrations, had broad spectrums of activity against bacterial, fungal and
      viral pathogens, and could easily be manipulated to alter their specificities,
      reduce their cytotoxicities and increase their antimicrobial activities.
      Unfortunately, commercial development of these peptides, for even the simplest of
      applications, has been very limited. With some peptides there are obstacles with
      their manufacture, in vivo efficacy and in vivo retention. More recently, the
      focus has shifted. Contemporary research now uses a more sophisticated approach
      to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid
      AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and
      immobilised AMPs have all emerged with selective or 'targeted' antimicrobial
      activities, improved retention, or unique abilities that allow them to bind to
      medical or industrial surfaces. These groups of new peptides have creative
      medical and industrial application potentials to treat antibiotic-resistant
      bacterial infections and septic shock, to preserve food or to sanitise surfaces
      both in vitro and in vivo.

PMID- 21733663
TI  - Concomitant blockade of 5-HT(1A) receptor and 5-HT transporter: use of the Hunter
      Serotonin toxicity criteria in a clinical pharmacology study.
AB  - There is a potential risk that 5-HT(1A) receptor blockade combined with blockade
      of the 5-HT transporter by an SSRI may cause a toxic increase in 5-HT within the
      synapse, sparking concern for 'serotonin syndrome', a rare but potentially life
      threatening condition. We evaluated the safety and pharmacodynamics of the
      combination of the 5-HT(1A) antagonist lecozotan and the SSRI citalopram in a
      well-controlled Clinical Pharmacology Unit setting using the Hunter Serotonin
      Toxicity Criteria (HSTC), a set of validated decision rules featuring
      neurological and body temperature measurements, to detect any clinically relevant
      serotonin toxicity. Forty-three young healthy male subjects were randomized, to 2
      parallel double-blind treatment groups following a 10-day citalopram 40 mg run-in
      period: citalopram 40 mg/lecozotan 10mg or citalopram 40 mg/placebo for 9 days.
      Overall, the combined administration of active drugs was well tolerated, however,
      one subject experienced moderate hyperreflexia, tremor of the hands, and sweating
      of hands and feet after 3 days of combined treatment. The event prompted
      treatment withdrawal and was regarded as mild serotonin toxicity, as per the
      HSTC. The onset of the event was around the time of peak plasma concentrations
      (t(max)) of both lecozotan and citalopram, and its time course corresponds to the
      well-defined PK profile of lecozotan. No evidence of a PK interaction was
      detected trough lecozotan and citalopram plasma concentrations analysis. The
      utility of the HSTC in detecting the non-discrete group of symptoms commonly
      referred to as "serotonin toxicity" was demonstrated in this clinical
      pharmacology study combining two 5-HT agents in a clinically controlled setting.

PMID- 21733664
TI  - A comparison of lipase and trypsin encapsulated in mesoporous materials with
      varying pore sizes and pH conditions.
AB  - Immobilized enzymes have an advantage over enzymes free in solution in that they
      are easily recovered after completed reaction. In addition, immobilization often
      gives enhanced stability. Entrapment of an enzyme in the pores of a mesoporous
      material is an attractive procedure since the enzyme is immobilized without any
      covalent bonding to a support which may be detrimental to the catalytic
      performance. The objective of this work is to compare the encapsulation and
      catalytic performance of lipase from Mucor miehei and trypsin from bovine
      pancreas, two hydrolases with rather dissimilar properties and structures. We
      also demonstrate the importance of the pore dimensions and the pH for proper
      function of the encapsulated enzyme. Mesoporous silica particles (SBA-15) with
      three different pore sizes (50 A, 60 A and 89 A) were synthesized and hexagonal
      structures with narrow pore size distributions were confirmed with TEM, SAXS and
      N(2)-adsorption. Lipase and trypsin were encapsulated separately in the silica
      particles and the results indicate distinct differences between the two enzymes,
      both in loading capacity and catalytic activity. For trypsin the encapsulation
      rate and the loading capacity were large with a maximum reached at pH 7.6. The
      largest product yield was obtained with the particles with 60 A pores, however,
      the yield was significantly lower than with free trypsin. For lipase optimal
      encapsulation rate and loading capacity were reached with the particles with 89 A
      pores at pH 6.0 but were low compared to trypsin. However, the catalytic activity
      of the encapsulated lipase was more than twice as large as for free lipase, which
      can be explained by an interfacial activation of lipase at the silica surface.

PMID- 21733665
TI  - [Antibiotic therapy of bone and joint infections in children: recent changes].
AB  - Management of bone and joint infections in children associates early appropriate
      antibiotic therapy against Staphylococcus aureus and Kingella kingae and, if
      necessary, surgical drainage of abscess or septic arthritis. In 2007, the
      Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP)
      proposed guidelines for antibiotherapy in acute and non-complicated cases, with
      an intravenous therapy during 4 to 7 days followed by oral therapy during 3
      weeks.

PMID- 21733666
TI  - Membranes and organelles. Editorial overview.

PMID- 21733667
TI  - Explaining drug policy: Towards an historical sociology of policy change.
AB  - The goal of seeking to understand the development over time of drug policies is a
      specific version of the more general intellectual project of finding ways of
      explaining social change. The latter has been a preoccupation of some of the
      greatest thinkers within the social sciences of the last 200 years, from Foucault
      all the way back to the three nineteenth-century pioneers, Marx, Durkheim and
      Weber. I describe this body of work as 'historical sociology'. In this paper, I
      outline how a particular approach to historical sociology can be fruitfully drawn
      upon to understand the development of drug policy, using by way of illustration
      the example of the analysis of a recent transformation in British drug policy:
      the rise of the criminal justice agenda. I conclude by arguing that by looking at
      developments in drug policy in this way, some new insights are opened up.

PMID- 21733668
TI  - Synthesis of functional SiO2-coated graphene oxide nanosheets decorated with Ag
      nanoparticles for H2O2 and glucose detection.
AB  - In this paper, we report on the first preparation of well-defined SiO(2)-coated
      graphene oxide (GO) nanosheets (SiO(2)/GO) without prior GO functionalization by
      combining sonication with sol-gel technique. The functional SiO(2)/GO
      nanocomposites (F-SiO(2)/GO) obtained by surface functionalization with NH(2)
      group were subsequently employed as a support for loading Ag nanoparticles
      (AgNPs) to synthesize AgNP-decorated F-SiO(2)/GO nanosheets (AgNP/F-SiO(2)/GO) by
      two different routes: (1) direct adsorption of preformed, negatively charged
      AgNPs; (2) in situ chemical reduction of silver salts. The morphologies of these
      nanocomposites were characterized by transmission electron microscopy (TEM) and
      scanning electron microscopy (SEM). It is found that the resultant AgNP/F
      SiO(2)/GO exhibits remarkable catalytic performance for H(2)O(2) reduction. This
      H(2)O(2) sensor has a fast amperometric response time of less than 2s. The linear
      range is estimated to be from 1*10(-4) M to 0.26 M (r=0.998) and the detection
      limit is estimated to be 4 * 10(-6) M at a signal-to-noise ratio of 3,
      respectively. We also fabricated a glucose biosensor by immobilizing glucose
      oxidase (GOD) into AgNP/F-SiO(2)/GO nanocomposite-modified glassy carbon
      electrode (GCE) for glucose detection. Our study demonstrates that the resultant
      glucose biosensor can be used for the glucose detection in human blood serum.

PMID- 21733669
TI  - Bio-Photonic Sensing Cells over transparent substrates for anti-gestrinone
      antibodies biosensing.
AB  - In a previous work we introduced the term Bio-Photonic Sensing Cells (BICELLs),
      referred to periodic networks of nano-pillar suitable for biosensing when are
      vertically interrogated. In this article, we demonstrate the biosensing
      capabilities of a type of micrometric size BICELLs made of SU-8 nano-pillars
      fabricated over transparent substrates. We verify the biochips functionality
      comparing the theoretical simulations with the experimental results when are
      optically interrogated in transmission. We also demonstrate a sensitivity
      enhancement by reducing the pitch among nano-pillars from 800 to 700 nm. Thus,
      the Limit of Detection achievable in these types of BICELLs is in the order of 64
      pg/mL for 700 nm in pitch among nano-pillars in comparison with 292 pg/mL for 800
      nm in pitch when are interrogated by Fourier Transform Visible and Infrared
      Spectrometry. The experiments exhibited a good reproducibility with a relative
      standard deviation of 0.29% measured within 8 days for a specific concentration.
      Finally, BICELLs functionality was tested in real conditions with unpurified
      rabbit serum for detecting anti-gestrinone antibodies, demonstrating the high
      performance of this type of BICELLs to detect specific antibodies having
      immobilized the suitable bioreceptors onto the sensing surface.

PMID- 21733670
TI  - Label-free colorimetric and quantitative detection of cancer marker protein using
      noncrosslinking aggregation of Au/Ag nanoparticles induced by target-specific
      peptide probe.
AB  - Assays for non-enzyme protein based on peptide-protein interaction are few due to
      the fact that most of peptide-protein bindings do not produce easily measurable
      output signals. Here we report a homogenous assay for colorimetric and
      quantitative detection of a cancer marker and promising antitumor target, cyclin
      A(2), using noncrosslinking aggregation of unmodified AuNPs/AgNPs by utilizing
      the difference of coagulating ability of a cationic peptide probe (P1) and its
      binding form toward naked AuNPs/AgNPs. In the absence of cyclin A(2), P1
      coagulates particles immediately, whereas cyclin A(2) binding prevents the
      interaction of P1 with metal particles surface, significantly reducing the
      magnitude of aggregation. The extent of aggregation is dependent on the
      concentration of the target protein cyclin A(2) and the difference in color can
      readily be distinguished by spectrometer and naked eyes. The assay is sensitive
      and selective. Cyclin A(2) assay using AuNPs as colorimetric indicator is more
      easily monitored by naked eyes owing to the distinct color change, and 40 nM
      cyclin A(2) can be detected without the aid of any instruments. Using inexpensive
      desktop spectrometer, cyclin A(2) assay using AgNPs as colorimetric indicator can
      detect as low as 30 nM cyclin A(2), which is 20 fold lower than that of cyclin
      A(2) assay using terbium-chelating peptide as the probe reported recently (Pazos
      et al., 2008, 130, 9652-9653). This strategy will shed light on developing of
      unlabeled peptide-based protein biosensors.

PMID- 21733671
TI  - Optimized ferrocene-functionalized ZnO nanorods for signal amplification in
      electrochemical immunoassay of Escherichia coli.
AB  - A novel amplified electrochemical immunoassay based on ferrocene (Fc)
      functionalized ZnO nanorods (NRs) was developed in the present work. The
      detection antibody ((d)Ab) and Fc were immobilized onto the surface of ZnO NRs,
      denoted as {(d)Ab-ZnO-Fc} bioconjugates. The amount of (d)Ab and Fc in the
      bioconjugates was investigated using the copper reduction/bicinchoninic acid
      reaction (BCA protein assay) and inductive coupled plasma-atomic emission
      spectroscopy (ICP-AES), respectively. Greatly amplified signal was achieved in
      the sandwich-type immunoassay when (d)Ab and Fc linked to ZnO NRs at a proper
      ratio. Using Escherichia coli (E. coli) as a model antigen, the designed
      immunoassay showed an excellent analytical performance, and exhibited a wide
      dynamic response range of E. coli concentration from 10(2) to 10(6)cfu/mL with a
      detection limit of 50 cfu/mL (S/N=3). By introducing a pre-enrichment step, the
      detection of 5 cfu/10 mL E. coli in hospital sewage water was realized. This
      proposed signal amplification strategy was promising and could be easily extended
      to monitor other biorecognition events.

PMID- 21733673
TI  - Moving, sensing and learning with cerebellar damage.
AB  - The cerebellum is a subcortical brain structure that is essential for learning
      and controlling movement. Recent work shows that the cerebellum also plays a role
      in certain perceptual abilities, beyond what would be expected secondary to poor
      movement control. This review covers these and other recent advances, focusing on
      how cerebellar damage affects human abilities ranging from sensory perception to
      movement control and motor learning.

PMID- 21733672
TI  - Synaptic microcircuit dysfunction in genetic models of neurodevelopmental
      disorders: focus on Mecp2 and Met.
AB  - Recent findings in the genetics of neurodevelopmental syndromes have ushered in
      an exciting era of discovery in which substrates of neurologic dysfunction are
      being identified at the synaptic and microcircuit levels in mouse models of these
      disorders. We review recent progress in this area, focusing on two examples of
      mouse models of autism spectrum disorders (ASDs): Mecp2 models of Rett syndrome,
      and a Met-knockout model of non-syndromic forms of autism. In both cases, a
      dominant theme is changes in synaptic strength, associated with hyper
      connectivity or hypo-connectivity in specific microcircuits. Alterations in
      intrinsic neuronal excitability are also found, but do not appear to be as
      common. The microcircuit-specific nature of synaptic changes observed in these
      ASD models indicates that it will be necessary to define mechanisms of circuit
      dysfunction on a case-by-case basis, not only in neocortex but also in brainstem
      and other sub-cortical areas. Thus, functional microcircuit analysis is emerging
      as an important line of investigation, highly complementary to neurogenetic and
      molecular strategies, and holds promise for generating models of the underlying
      pathophysiology and for guiding development of novel therapeutic strategies.

PMID- 21733674
TI  - Clinical management of primary vulvar cancer.
AB  - AIMS: Vulvar cancer is a rare disease with increasing incidence over the last
      decades. Treatment includes surgical, radio- and chemotherapeutical options;
      however, due to the low incidence of the disease and the lack of randomised
      trials many questions regarding indication of different treatment approaches
      remain unanswered. This article discusses the current literature to elaborate
      recommendations for the management of primary vulvar cancer in clinical routine.
      METHODS: We reviewed the available literature on treatment of invasive vulvar
      cancer with emphasis on therapeutic strategies such as surgery and
      radio/chemotherapy. RESULTS: Surgery of the primary tumour and the groins remain
      the cornerstone of treatment in vulvar cancer with a strong trend towards a less
      radical approach in early stage disease. Complete vulvectomy was replaced by
      radical local excision with plastic reconstruction and the sentinel node
      technique was implemented to avoid the morbidity of complete groin dissection in
      node negative patients. In patients with advanced primary disease, treatment
      decisions are still a challenge. Criteria for the indication and performance of
      chemo/radiotherapy of the vulva/groins/pelvis are still not fully established and
      vary between different countries and institutions due to the low level of
      evidence. Often an individualised therapeutic approach aside from guidelines is
      necessary to treat these patients adequately. CONCLUSIONS: To enable reasonable
      treatment decisions and avoid unnecessary morbidity, treatment in specialised
      centres should be intended at any time. Clinical studies performed by several
      study groups on an international level are urgently needed to further improve
      therapy.

PMID- 21733675
TI  - Treatment with curative intent of stage III non-small cell lung cancer patients
      of 75 years: a prospective population-based study.
AB  - BACKGROUND: There is little data on the survival of elderly patients with stage
      III non-small cell lung cancer (NSCLC). METHODS: Patients with stage III NSCLC in
      the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008
      were included. FINDINGS: One thousand and two patients with stage III were
      diagnosed, of which 237 were 75 years or older. From 228 patients, co-morbidity
      scores were available. Only 33/237 patients (14.5%) had no co-morbidities, 195
      (85.5%) had one or more important co-morbidities, 60 (26.3%) two or more co
      morbidities, 18 (7.9%) three or more co-morbidities and 2 patients (0.9%)
      suffered from four co-morbidities. Forty-eight percent were treated with curative
      intent. No significant difference in Charlson co-morbidity, age or gender was
      found between patients receiving curative or palliative intent treatment.
      Treatment with curative intent was associated with increased overall survival
      (OS) compared to palliative treatment: median OS 14.2 months (9.6-18.7) versus
      5.2 months (4.3-6.0), 2-year OS 35.5% versus 12.1%, for curative versus
      palliative treatment. FINDINGS: Patients who received only radiotherapy with
      curative intent had a median OS of 11.1 months (95% confidence interval [95% CI]
      6.4-15.8) and a 5-year OS of 20.3%; for sequential chemotherapy and radiotherapy,
      the median OS was 18.0 months (95% CI 12.2-23.7), with a 5-year OS of 14.9%. Only
      four patients received concurrent chemo-radiation. INTERPRETATION: In this
      prospective series treating elderly patients with stage III NSCLC with curative
      intent was associated with significant 5-year survival rates.

PMID- 21733676
TI  - Body mass index and risk of non-Hodgkin's and Hodgkin's lymphoma: a meta-analysis
      of prospective studies.
AB  - We conducted a meta-analysis of prospective studies to summarise the
      epidemiologic evidence regarding the association of body mass index (BMI) with
      non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) incidence and NHL
      mortality. Pertinent studies were identified by searching PubMed (1966-May 2011)
      and the reference lists of retrieved articles. For each study, we estimated a
      relative risk (RR) for a 5 kg/m(2) increase in BMI. A random-effects model was
      used to combine the RR estimates from individual studies. The summary RRs for a 5
      kg/m(2) increase in BMI were 1.07 (95% confidence intervals (CI), 1.04-1.10) for
      NHL incidence (16 studies, n=17,291 cases) and 1.14 (95% CI, 1.04-1.26) for NHL
      mortality (five studies, n=3407 cases). BMI was significantly positively
      associated with risk of diffuse large B-cell lymphoma (RR, 1.13; 95% CI, 1.02
      1.26), but not other NHL subtypes. The difference in risk estimates for subtypes
      was not statistically significant (P=0.10). There was evidence of a nonlinear
      association between BMI and HL (P for nonlinearity=0.01) (five studies, n=1557
      cases). The summary RRs of HL were 0.97 (95% CI, 0.85-1.12) for overweight and
      1.41 (95% CI, 1.14-1.75) for obesity. These results indicate that BMI is
      positively associated with risk of NHL and HL as well as with NHL mortality.

PMID- 21733677
TI  - Chewing areca nut, betel quid, oral snuff, cigarette smoking and the risk of
      oesophageal squamous-cell carcinoma in South Asians: a multicentre case-control
      study.
AB  - Oesophageal cancer remains an important public health problem worldwide. This
      multicentre matched case-control study examined the chewing areca nut alone,
      betel quid with tobacco, oral snuff (snuff dipping) and cigarette smoking as the
      risk factors for oesophageal squamous-cell carcinoma. We enrolled 91 cases of
      oesophageal squamous-cell carcinoma and 364 matched controls from three tertiary
      care hospitals in Karachi, Pakistan. A structured questionnaire was used to
      collect the data through face-to-face interview of the participants.
      Multivariable conditional logistic regression model showed that after adjusting
      for the effect of ethnicity, ever chewed areca nut alone (adjusted matched odds
      ratio (mOR(adj))=3.7; 95% confidence interval (CI): 1.6-8.5), ever chewed betel
      quid with tobacco (mOR(adj)=12.8; 95% CI: 6.3-26.2), ever practiced snuff dipping
      (mOR(adj)=4.3; 95% CI: 1.6-11.7) and ever smoked cigarettes (mOR(adj)=2.9; 95%
      CI: 1.4-5.9) were significantly and independently associated with oesophageal
      squamous-cell carcinoma status. The adjusted summary population attributable risk
      (PAR) percent for all four substances together was 67.0. Furthermore, despite
      incomplete synergy, there was manifold increase in the risk of oesophageal
      squamous-cell carcinoma, if the respondents ever smoked cigarettes and ever
      chewed betel quid with tobacco (mOR(adj)=21.4; 95% CI: 6.3-72.4) or if they ever
      smoked cigarettes and ever practiced snuff dipping (mOR(adj)=14.4; 95% CI: 2.3
      91.1). The adjusted PAR (%) was higher for the dual practice of smoking
      cigarettes and chewing betel quid with tobacco (64.3) than the dual practice of
      smoking cigarettes and snuff dipping (32.2). Public awareness to curtail the
      addiction to these substances may result in a substantial reduction in the
      incidence of oesophageal squamous-cell carcinoma and related mortality in this
      and similar settings.

PMID- 21733678
TI  - Cancer and pregnancy: a comprehensive review.
AB  - BACKGROUND: Pregnancy complicated by cancer is relatively rare but, as women in
      western societies tend to delay childbearing to the third and fourth decade of
      life, this phenomenon is going to be encountered more often in the future.
      MATERIAL AND METHODS: Review of the literature and description of the different
      diagnostic and therapeutic approaches which are required to diagnose and treat
      pregnant mothers with cancer. RESULTS: As in non-pregnant patients, every effort
      should be made to provide the maximal benefit and best prognosis to the pregnant
      patient. In most cases, in order to avoid any harm to the fetus, different
      diagnostic approach should be incorporated and treatment should be tailored to
      each pregnant woman. Cooperation of multidisciplinary teams, incorporating
      medical and radiation oncologists, surgeons, obstetricians, neonatologists and
      experienced nursing staff, is required to provide optimal care for the patient.
      The benefits from use of surgery, chemotherapy and/or radiotherapy as well as the
      mother's wishes and beliefs need to be factored into recommendations and
      treatment planning. CONCLUSIONS: With the experience gained, the developments in
      clinical and radiation oncology and the cooperation of multidisciplinary teams,
      treatment of cancer during pregnancy with normal fetal outcome is feasible.

PMID- 21733679
TI  - Production of leucine amino peptidase in lab scale bioreactors using Streptomyces
      gedanensis.
AB  - Studies were conducted on the production of leucine amino peptidase (LAP) by
      Streptomyces gedanensis to ascertain the performance of the process in shake
      flask, parallel fermenter and 5-L fermenter utilizing soy bean meal as the carbon
      source. Experiments were conducted to analyze the effects of aeration and
      agitation rate on cell growth and LAP production. The results unveiled that an
      agitation rate of 300 rpm, 50% dissolved oxygen (DO) upholding and 0.15 vvm
      strategies were the optimal for the enzyme production, yielding 22.72 +/- 0.11
      IU/mL LAP in parallel fermenter which was comparable to flask level (24.65 +/-
      0.12 IU/mL LAP) fermentation. Further scale-up, in 5-L fermenter showed 50% DO
      and 1 vvm aeration rate was the best, producing optimum and the production was
      20.09 +/- 0.06 IU/mL LAP. The information obtained could be useful to design a
      strategy to improve a large-scale bioreactor cultivation of cells and production
      of LAP.

PMID- 21733680
TI  - Current status of the metabolic engineering of microorganisms for biohydrogen
      production.
AB  - The improvement of H2 production capabilities of hydrogen (H2)-producing
      microorganisms is a challenging issue. Microorganisms have evolved for fast
      growth and substrate utilization rather than H2 production. To develop good H2
      producing biocatalysts, many studies have focused on the redirection and/or
      reconstruction of cellular metabolisms. These studies included the elimination of
      enzymes and carbon pathways interfering or competing with H2 production, the
      incorporation of non-native metabolic pathways leading to H2 production, the
      utilization of various carbon substrates, the rectification of H2-producting
      enzymes (nitrogenase and hydrogenase) and photophosphorylation systems, and in
      silico pathway flux analysis, among others. Owing to these studies, significant
      improvements in the yield and rate of H2 production, and in the stability of H2
      production activity, were reached. This review presents and discusses the recent
      developments in biohydrogen production, with a focus on metabolic pathway
      engineering.

PMID- 21733681
TI  - Structural characterization and antioxidant properties of an exopolysaccharide
      produced by the mangrove endophytic fungus Aspergillus sp. Y16.
AB  - A homogeneous exopolysaccharide, designated As1-1, was obtained from the culture
      medium of the mangrove endophytic fungus Aspergillus sp. Y16 and purified by
      anion-exchange and gel-permeation chromatography. Results of chemical and
      spectroscopic analyses, including one- and two-dimensional nuclear magnetic
      resonance (1D and 2D NMR) spectroscopy showed that As1-1 was mainly composed of
      mannose with small amounts of galactose, and that its molecular weight was about
      15 kDa. The backbone of As1-1 mainly consists of (1->2)-linked alpha-d
      mannopyranose units, substituted at C-6 by the (1->6)-linked alpha-d
      mannopyranose, (1->)-linked beta-d-galactofuranose and (1->)-linked beta-d
      mannopyranose units. As1-1 possessed good in vitro antioxidant activity as
      evaluated by scavenging assays involving 1,1-diphenyl-2-picrylhydrazyl (DPPH) and
      superoxide radicals. The investigation demonstrated that As1-1 is an
      exopolysaccharide different from those of other marine microorganisms, and could
      be a potential antioxidant and food supplement.

PMID- 21733682
TI  - Synthesis and antihistamine evaluations of novel loratadine analogues.
AB  - A series of loratadine analogues containing hydroxyl group and chiral center were
      synthesized. The effect of the synthesized compounds on the histamine-induced
      contractions of guinea-pig ileum muscles was studied. In addition, the in vivo
      asthma-relieving effect of the analogues in the histamine induced asthmatic
      reaction in guinea-pigs was determined. Most of the compounds exhibited definite
      H(1) antihistamine activity. The S-enantiomers, compounds 2, 4 and 8, are more
      potent than the R-enantiomers, compounds 1, 3 and 7. Compound 6 was the most
      active one among the eight synthesized compounds.

PMID- 21733683
TI  - Structure-activity study on a series of alpha-glutamic acid scaffold based
      compounds as new ADAMTS inhibitors.
AB  - A series of alpha-glutamic acid scaffold based 4-(benzamido)-4-(1,3,4-oxadiazol-2
      yl) butanoic acids were designed and synthesized as new ADAMTS inhibitors. The
      compounds dose-dependently inhibited the enzymatic activities of ADAMTS-4 and
      ADAMTS-5. One of the most active compound 2h potently inhibited ADAMTS-4 and
      ADAMTS-5 with IC(50) values of 1.2 and 0.8 MUM, respectively. These inhibitors
      may serve as new lead compounds for further development of therapeutics to treat
      osteoarthritis.

PMID- 21733684
TI  - Structure-activity studies of RNA-binding oxazolidinone derivatives.
AB  - The structure-activity relationship of a series of oxazolidinones binding to T
      box riboswitch antiterminator RNA has been investigated. Oxazolidinones
      differentially substituted at C-5 were prepared and the ligand-induced
      fluorescence resonance energy transfer (FRET) changes in FRET-labeled
      antiterminator model RNA were assayed. Both qualitative and quantitative analysis
      of the structure-activity relationship indicate that hydrogen bonding and
      hydrophobic properties play a significant role in ligand binding.

PMID- 21733685
TI  - Hydrophobic tag-assisted liquid-phase synthesis of a growth hormone-inhibiting
      peptide somatostatin.
AB  - Hydrophobic tag-assisted liquid-phase peptide synthesis technique and disulfide
      bond formation have been well-combined, leading to the efficient and practical
      preparation of a growth hormone-inhibiting peptide somatostatin. Intramolecular
      disulfide bond formation has successfully been carried out even under relatively
      high concentrations, enabling the effective peptide modifications in preparative
      scale.

PMID- 21733686
TI  - Antiproliferative activity and QSAR studies of a series of new 4-aminomethylidene
      derivatives of some pyrazol-5-ones.
AB  - Twenty five 4-aminomethylidene derivatives obtained from 3-phenyl-2-pyrazolin-5
      one and 1,3-diphenyl-2-pyrazolin-5-one were synthesized and tested for their
      antiproliferative activity against human breast cancer MDA-MB-361 and MDA-MB-453
      cell lines. The compounds derived from 1,3-diphenyl-2-pyrazolin-5-one exhibited
      the most remarkable activity in the treatment of both cell lines. In vitro
      antiproliferative activities were accompanied by an important apoptotic fraction
      of both cell lines; also, compounds inhibited key endothelial cell functions
      implicated in invasion and angiogenesis. QSAR methods were performed in order to
      analyze the influence of structural features of the compounds investigated on the
      antiproliferative potential on MDA-MB-361 and MDA-MB-453 cancer cells. One
      parameter heuristic analysis was performed and different whole molecule and
      fragmental descriptors were considered for rationalization of mechanism of
      interaction of these compounds with active place of hypothetical target included
      in tumorigenesis.

PMID- 21733687
TI  - Limonoids from seeds of Thai Xylocarpus moluccensis.
AB  - A new andirobin, thaimoluccensin A (1), and two new phragmalin-type limonoids,
      thaimoluccensins B (2) and C (3), were isolated from seeds of a Thai mangrove
      plant, Xylocarpus moluccensis, together with eight known compounds. The
      structures of these compounds were elucidated on the basis of spectroscopic data.
      Only 7-deacetylgedunin (7), a gedunin-type limonoid, exhibited significant
      inhibitory activity against nitric oxide production from activated macrophages
      with IC(50) value less than 10 MUM, suggesting that the compound has anti
      inflammatory activity.

PMID- 21733688
TI  - Design, synthesis and antimycobacterial evaluation of novel 3-substituted-N-aryl
      6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide analogues.
AB  - In the present investigation, a series of 3-substituted-N-aryl-6,7-dimethoxy-3a,4
      dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide analogues were synthesized and
      were evaluated for antitubercular activity by two fold serial dilution technique.
      All the newly synthesized compounds showed moderate to high inhibitory activities
      against Mycobacterium tuberculosis H(37)Rv and INH resistant M. tuberculosis. The
      compound N,3-bis(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2
      c]pyrazole-2-carboxamide (4c) was found to be the most promising compound active
      against M. tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis with
      minimum inhibitory concentration 0.78 MUM.

PMID- 21733689
TI  - Simple but powerful: phenanthroline-based small molecules for cellular imaging
      and cancer screening.
AB  - A two-step synthetic procedure gives highly fluorescent phenanthroline molecular
      probes. The compounds localize in the endoplasmic reticulum and their potential
      as bioactive probes was evaluated. The materials are quickly taken up by living
      cells within 5 min. Preliminary in vitro studies have shown that these compounds
      are selective to esophageal cancer cells and can be used as selective markers in
      intracellular cancer diagnostics. The materials show a remarkable cytotoxicity
      towards cancer cells vs normal as 7-1.

PMID- 21733690
TI  - Benzimidazolone as potent chymase inhibitor: modulation of reactive metabolite
      formation in the hydrophobic (P1) region.
AB  - A new class of chymase inhibitor featuring a benzimidazolone core with an acid
      side chain and a P(1) hydrophobic moiety is described. Incubation of the lead
      compound with GSH resulted in the formation of a GSH conjugate on the
      benzothiophene P(1) moiety. Replacement of the benzothiophene with different
      heterocyclic systems such as indoles and benzoisothiazole is feasible. Among the
      P(1) replacements, benzoisothiazole prevents the formation of GSH conjugate and
      an in silico analysis of oxidative potentials agreed with the experimental
      outcome.

PMID- 21733691
TI  - Nothospondin, a new AP-1 inhibitory quassinoid from the Cameroonian plant
      Nothospondias staudtii.
AB  - A high throughput screen for inhibitors of the oncogenic transcription factor
      activator protein-1 (AP-1) was applied to the NCI repository of natural product
      extracts. The liphophilic extract of the plant Nothospondias staudtii
      (Simaroubaceae) displayed significant AP-1 inhibition. Bioassay-guided
      fractionation of the extract lead to a new quassinoid named nothospondin (1), and
      the known compound glaucarubinone (2). The structure of 1 was elucidated by
      spectroscopic methods. Compounds 1 and 2 showed potent, dose-dependent AP-1
      inhibition at noncytotoxic concentrations.

PMID- 21733692
TI  - Azepanone-based inhibitors of human cathepsin S: optimization of selectivity via
      the P2 substituent.
AB  - A series of azepanone inhibitors of cathepsin S is described. Selectivity over
      both cathepsin K and cathepsin L was achieved by varying the P2 substituent.
      Ultimately, a balanced potency and selectivity profile was achieved in compound
      39 possessing a 1-methylcyclohexyl alanine at P2 and nicotinamide as the P'
      substituent. The cellular potency of selected analogs is also described.

PMID- 21733693
TI  - Development of potent B-RafV600E inhibitors containing an arylsulfonamide
      headgroup.
AB  - A potent series of inhibitors against the B-Raf(V600E) kinase have been developed
      that show excellent activity in cellular assays and good oral bioavailability in
      rats. The key structural features of the series are an arylsulfonamide headgroup,
      a thiazole core, and a fluorine ortho to the sulfonamide nitrogen.

PMID- 21733694
TI  - Mechanical energy transfers across lower limb segments during stair ascent and
      descent in young and healthy older adults.
AB  - Older adults present with altered movement patterns during stair negotiation
      although the extent to which modifications in pattern and speed influence
      mechanical efficiency is unknown. This study evaluated mechanical energy
      transfers attributed to active force production during stair negotiation in young
      and older adults to provide insight into age-related changes in mechanical
      efficiency. Secondary analysis on data obtained from 23 young (23.7+/-3.0 years)
      and 32 older adults (67.0+/-8.2 years) during self-paced stair ascent and descent
      was conducted. Mechanical energy expenditures (MEE) during concentric transfer,
      eccentric transfer and no-transfer phases were determined for the ankle, knee and
      hip power profiles in the sagittal plane. Mechanical energy compensations (MEC)
      were also determined at each joint. During ascent, MEEs were similar for young
      and older adults although older adults compensated ankle muscles to a lesser
      extent during concentric muscle action. Controlling for cadence eliminated this
      difference. During descent, older adults demonstrated lower energy expenditures
      at the ankle and hip and similar expenditures at the knee compared to young
      adults. Changes in joint MEE in the older group resulted in reduced energy
      compensation at the ankle during concentric and eccentric activity and at the
      knee during eccentric activity. These age-related differences in mechanical
      energy transfers and related adjustments in MEC were not a function of the slower
      cadence in older adults and suggest a loss in mechanical efficiency. These
      results provide a benchmark against which physical impairments in older adults
      may be explored.

PMID- 21733695
TI  - Walking while resisting a perturbation: Effects on ankle dorsiflexor activation
      during swing and potential for rehabilitation.
AB  - Motor control studies have shown that when walking is performed while resisting a
      perturbation applied to the lower limb, the muscle activation pattern can be
      temporarily modified. The objective of the present study is to validate if such
      an approach, targeting the ankle, could specifically promote an increased
      activation of the ankle dorsiflexor muscles that are of key importance for the
      rehabilitation of foot drop. METHODS: 12 adults, with no gait deficit, walked on
      a treadmill for three periods of 5min: before, during and after exposure to a
      torque perturbation applied by a robotized ankle-foot orthosis that tended to
      plantarflex the ankle during the swing phase. Spatiotemporal gait parameters,
      ankle and knee kinematics, and the electromyographic activity of five lower limb
      muscle groups were recorded. RESULTS: The perturbation initially caused a
      deviation of the ankle towards plantarflexion. This movement error was rapidly
      reduced and associated with a large increase (78.2%; p<0.001) in tibialis
      anterior (ankle dorsiflexor; TA) activation, specifically in the stance-to-swing
      burst. This increase carried over to post-perturbation walking, gradually
      disappearing over several strides. Interestingly, these aftereffects led to an
      increase in peak ankle dorsiflexion of approximately 7 degrees  during the swing
      phase. CONCLUSIONS: Walking while resisting a torque perturbation applied at the
      ankle during swing promotes an increase in TA muscle activation that carries over
      after perturbation removal, leading to an increased ankle dorsiflexion. Training
      based on this approach may have the potential of improving the gait of persons
      with foot drop.

PMID- 21733696
TI  - Effect of footwear on the external knee adduction moment - A systematic review.
AB  - CONTEXT: Footwear modifications have been investigated as conservative
      interventions to decrease peak external knee adduction moment (EKAM) and pain
      associated with knee osteoarthritis (OA). OBJECTIVE: To evaluate the literature
      on the effect of different footwear and orthotics on the peak EKAM during walking
      and/or running. METHODS: A systematic search of databases resulted in 348
      articles of which 33 studies were included. RESULTS: Seventeen studies included
      healthy individuals and 19 studies included subjects with medial knee OA. Quality
      assessment (modified Downs and Black quality index) showed an (average+/-SD) of
      73.1+/-10.1%. The most commonly used orthotic was the lateral wedge, with three
      studies on the medial wedge. Lateral wedging was associated with decreased peak
      EKAM in healthy participants and participants with medial knee OA while there is
      evidence for increased peak EKAM with the use of medial wedges. Modern footwear
      (subjects' own shoe, "stability" and "mobility" shoes, clogs) were likely to
      increase the EKAM compared to barefoot walking in individuals with medial knee
      OA. Walking in innovative shoes ("variable stiffness") decreased the EKAM
      compared to control shoes. Similarly, shoes with higher heels, sneakers and dress
      shoes increased EKAM in healthy individuals compared to barefoot walking.
      CONCLUSIONS: Further development may be needed toward optimal footwear for
      patients with medial knee OA with the aim of obtaining similar knee moments to
      barefoot walking.

PMID- 21733697
TI  - Reducing blood loss in primary knee arthroplasty: a prospective randomised
      controlled trial of tranexamic acid and fibrin spray.
AB  - A prospective, randomised controlled trial compared the effects of two
      medications intended to reduce blood loss from total knee arthroplasty. Patients
      were randomised to one of the following three treatment groups: 10mg/kg
      tranexamic acid at given at induction of anaesthesia, 10 ml of fibrin spray
      administered topically during surgery, or to a control group receiving neither
      treatment. Sixty six patients underwent elective cemented total knee
      arthroplasty; computer navigation was used in all cases. There was no significant
      difference in blood loss between the tranexamic acid and fibrin spray groups
      (p=0.181). There was no significant difference in blood loss between the
      tranexamic acid and fibrin spray groups(p=0.181). The fibrin spray led to a
      significant reduction in blood loss compared to control (p=0.007). The effect of
      tranexamic acid did not reach significance (p=0.173). We conclude that fibrin
      spray was effective in reducing blood loss but that with a study of this power,
      we were unable to detect an effect of tranexamic acid in cemented navigated total
      knee replacement at the dose used.

PMID- 21733698
TI  - Design, synthesis and biological evaluation of tyrosine-based hydroxamic acid
      analogs as novel histone deacetylases (HDACs) inhibitors.
AB  - Histone deacetylases (HDACs) are a promising target for treating cancer and some
      other disorders. Herein, based on the structure of our previously reported
      tetrahydroisoquinoline-based hydroxamic acids, a novel series of tyrosine-based
      hydroxamic acid derivatives was designed and synthesized as HDACs inhibitors.
      Compared with tetrahydroisoquinoline-based hydroxamic acids, tyrosine-based
      hydroxamic acid derivatives exhibited more potent HDAC8 inhibitory activity.
      However, the antiproliferative activities and HeLa cell nuclear extract
      inhibition of several selected tyrosine-based hydroxamic acids were moderate.

PMID- 21733699
TI  - Requirements for mammalian carboxylesterase inhibition by substituted ethane-1,2
      diones.
AB  - Carboxylesterases (CE) are ubiquitous enzymes found in both human and animal
      tissues and are responsible for the metabolism of xenobiotics. This includes
      numerous natural products, as well as a many clinically used drugs. Hence, the
      activity of these agents is likely dependent upon the levels and location of CE
      expression. We have recently identified benzil is a potent inhibitor of mammalian
      CEs, and in this study, we have assessed the ability of analogues of this
      compound to inhibit these enzymes. Three different classes of molecules were
      assayed: one containing different atoms vicinal to the carbonyl carbon atom and
      the benzene ring [PhXC(O)C(O)XPh, where X=CH2, CHBr, N, S, or O]; a second
      containing a panel of alkyl 1,2-diones demonstrating increasing alkyl chain
      length; and a third consisting of a series of 1-phenyl-2-alkyl-1,2-diones. In
      general, with the former series of molecules, heteroatoms resulted in either loss
      of inhibitory potency (when X=N), or conversion of the compounds into substrates
      for the enzymes (when X=S or O). However, the inclusion of a brominated methylene
      atom resulted in potent CE inhibition. Subsequent analysis with the alkyl diones
      [RC(O)C(O)R, where R ranged from CH3 to C8H17] and 1-phenyl-2-alkyl-1,2-diones
      [PhC(O)C(O)R where R ranged from CH3 to C6H13], demonstrated that the potency of
      enzyme inhibition directly correlated with the hydrophobicity (clogP) of the
      molecules. We conclude from these studies that that the inhibitory power of these
      1,2-dione derivatives depends primarily upon the hydrophobicity of the R group,
      but also on the electrophilicity of the carbonyl group.

PMID- 21733700
TI  - Treatment and complications of mandibular fractures: a 10-year analysis.
AB  - The surgical treatment and complications of patients with mandibular fractures in
      Amsterdam over a period of 10 years are analysed. Between January 2000 and
      January 2009 225 patients were surgically treated for a mandibular fracture (mean
      age of 32.6 (SD+/-14.6) years). A total of 426 fracture lines were identified. Of
      213 dentate patients 29 patients were treated primarily with intermaxillary
      fixation (IMF). IMF combined with osteosynthesis was performed on 99 patients.
      Seventy-nine patients received IMF only per-operatively to make open reduction
      and internal fixation (ORIF) possible. Of 12 edentulous patients three patients
      were treated with Gunning splints. Nine patients were treated by manual reduction
      and internal fixation. A total of 1965 screws and 442 plates were used. Sixty
      (26.7%) patients presented with complications, including (transient)
      hyposensibility of the lip and chin (34 patients), dysocclusion (15 patients),
      infected osteosynthesis material (six patients) and temporomandibular dysfunction
      (five patients). Four patients needed surgical retreatment for correction of a
      dysocclusion. The results of this report are partly in line with other studies
      and provide important data for improving the treatment of the fractured mandible.

PMID- 21733701
TI  - Oral health-related quality of life and depression/anxiety in long-term
      recurrence-free patients after treatment for advanced oral squamous cell cancer.
AB  - This report focuses on the association between oral health-related quality of
      life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients
      who were recurrence-free for 8 years after treatment for advanced oral squamous
      cell. Participants were 24 patients (mean age 55 years, 75% men) treated with
      neoadjuvant concurrent radiochemotherapy followed by surgery with a mean
      recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP)
      and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2).
      OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged
      correlation analysis, the correlation between OHRQoL to t1 and depression to t2
      was significant and greater than the non-significant correlation for depression
      to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than
      vice versa. However, the difference in the correlation coefficients was not
      significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL
      measured with the OHIP was impaired in comparison to the normal population. In
      the limitations of the study design and bearing the small sample size in mind,
      the results give evidence that OHRQoL predicts psychological outcomes, namely
      depression and anxiety, better than vice versa.

PMID- 21733702
TI  - Upper airway distress due to an oropharyngeal infantile myofibroma.
AB  - Infantile myofibroma is an uncommon fibrous tumour of infancy, usually present at
      birth. It is a rare cause of child airway obstruction, with only one neonatal
      case reported. We report an eight months age case which was referred to our Unit
      for increasing respiratory distress. CT scan showed a well defined margins mass
      measuring 7*5*5cm arising from the left parapharyngeal space and occupying the
      oropharynx. We performed a complete surgical resection through a transoral
      approach with no events during the surgery. The patient has been followed-up by
      the first author for five years with no signs of recurrence or sequelaes.

PMID- 21733703
TI  - Correlation between clinical findings and CT-measured displacement in patients
      with fractures of the zygomaticomaxillary complex.
AB  - BACKGROUND: This prospective clinical study aimed to analyse the influence of
      displacement on duration and severity of symptoms of fractures of the
      zygomaticomaxillary complex. METHODS: 47 patients, who received surgical
      treatment of zygomaticomaxillary complex fractures at the Department of Oral and
      Maxillofacial Surgery/Plastic Surgery, University Hospital Jena were examined
      preoperatively, 1, 3 and 10 days as well as 6 months post-operation for
      ophthalmologic, occlusal and neurosensory changes. RESULTS: Preoperatively,
      periorbital haematoma and ooedema were present in 76.6% and 31.9% of the
      patients, which increased until day 1 post-op and decreased until the end of
      hospital stay. Preoperative diplopia was present in 83.0% of the patients and
      resolved postoperatively in all but 3 cases, in whom it persisted until end of
      the study. Occlusal disturbances and limited mouth opening were present in 21.3%
      of the patients and resolved by end of the study in all but 2 cases. Neither
      ophthalmologic nor occlusal changes correlated with the degree of displacement.
      Postoperatively no significant differences were detectable among the groups. In
      44.8% of the patients neurosensory disturbances persisted until end of the follow
      up. In the non-displaced fracture group none of the patients suffered from
      neurosensory disturbances at the 6-month follow-up. CONCLUSION: Although the
      degree of displacement has a significant impact on the incidence of sensory
      disturbances preoperatively, postoperatively no differences were observed between
      displaced and non-displaced fractures.

PMID- 21733704
TI  - Triple dumbbell-shaped jugular foramen schwannomas.
AB  - PURPOSE: Triple dumbbell-shaped jugular foremen schwannomas (DSJFSs) have high
      cervical extension according to Bulsara's classification. One-stage, single
      discipline, total removal of triple DSJFSs is not always possible due to their
      both intracranial and cervical extensions. We evaluated our experience in one
      stage resection of triple DSJFSs by using a combined neurosurgical and head and
      neck approach. METHODS: Between October 2004 and May 2009, eight patients with
      triple DSJFSs were treated surgically at our institute. The clinical and
      radiological features, operative procedures and outcomes are retrospectively
      reviewed. RESULTS: Total tumour removal was achieved in seven patients and near
      total in one. New cranial nerve (CN) paresis occurred after surgery in one
      patient and worsening of preoperative CN deficits was noted in three. Two
      patients experienced cerebrospinal fluid leakage and one of them had a repeated
      operation with closure of the dural deficit. Follow-up period ranged from 23 to
      60 months (mean 38 months). All CN dysfunction had improved considerably at the
      last follow-up examination. There have been no clinical or radiological signs of
      tumour recurrence. CONCLUSIONS: One-stage total resection of triple DSJFSs can be
      achieved by a multidisciplinary cranial base team composed of neurosurgeons and
      head and neck surgeons via a craniocervical approach.

PMID- 21733705
TI  - Multimodality imaging in the evaluation of aorta-right atrial tunnel.

PMID- 21733706
TI  - Isolated giant ascending aortic aneurysm in a child: a novel mutation of the
      ACTA2 gene.

PMID- 21733708
TI  - Effects of FP15, a peroxynitrite decomposition catalyst on cardiac and pulmonary
      function after cardiopulmonary bypass.
AB  - OBJECTIVE: Peroxynitrite, a toxic nitrogen species, has been implicated in the
      development of ischemia/reperfusion injury. The aim of the present study was to
      investigate the effects of the potent peroxynitrite decomposition catalyst, FP15,
      on myocardial, endothelial, and pulmonary function in an experimental model of
      cardioplegic arrest and extracorporal circulation. METHODS: Twelve anesthetized
      dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic
      cardiac arrest, reperfusion was started and either saline vehicle (control, n =
      6) or FP15 (n = 6) was administered. Left-ventricular preload-recruitable stroke
      work (PRSW) was measured by a combined pressure-volume conductance catheter at
      baseline and after 60 min of reperfusion. Left anterior descending (LAD) coronary
      (CBF) and pulmonary blood flow (PBF), endothelium-dependent vasodilatation to
      acetylcholine (ACh), and alveolo-arterial O2 gradient were determined. RESULTS:
      The administration of FP15 led to a significantly better recovery of PRSW (given
      as percent of baseline: 93 +/- 9 vs 62 +/- 6%, p < 0.05). CBF was also
      significantly higher in the FP15 group (44 +/- 6 vs 25 +/- 4 ml min(-1), p <
      0.05). Injection of ACh resulted in a significantly higher increase in CBF (70 +/
      6 vs 35 +/- 5%, p < 0.05) in the FP15-treated animals. The alveolo-arterial O2
      gradient was significantly lower after FP15 administration (83 +/- 7 vs 49 +/- 6
      mmHg, p < 0.05). Catalytic peroxynitrite decomposition did not affect baseline
      cardiovascular and pulmonary functions. CONCLUSIONS: Application of FP15 improves
      myocardial, endothelial, and pulmonary function after cardiopulmonary bypass with
      hypothermic cardiac arrest. The observed protective effects imply that catalytic
      peroxynitrite decomposition could be a novel therapeutic option in the treatment
      of ischemia/reperfusion injury.

PMID- 21733709
TI  - Pulmonary artery banding: still a valuable option in developing countries?
AB  - OBJECTIVE: We examined whether the socio-economic circumstances of a developing
      country justify pulmonary artery banding (PAB) for the deferral of perceived high
      risk patients requiring biventricular repair. METHODS: A retrospective cohort
      analysis was done on 143 consecutive patients with ventricular anatomy suitable
      for a biventricular repair, who had a pulmonary artery band applied between 1
      January 2002 and 31 December 2007 as they were considered too high a risk to
      undergo corrective surgery. The goal in all patients was to lower their risk of
      definitive surgery by improving their clinical condition. The minimum follow-up
      period was 2 years with the closing date for data collection being 31 January
      2010. The mean weight and age at PAB was 5.34 +/- 2.94 kg and 9.9 +/- 17.3
      months. The endpoints of the study were mortality, interval hospital readmission,
      growth pattern post-banding, whether or not definitive correction was achieved,
      and the current follow-up status of uncorrected patients. RESULTS: The hospital
      mortality was 8% (n = 12), the inter-stage mortality 21% (n = 30), and the total
      mortality 29% (n = 42). Positive growth was not shown in 50% following the
      banding procedure. The mean number of inter-current hospital admissions was 1.5
      +/- 2 times per patient. At the termination of data collection, after a mean
      interval of 24.5 +/- 14.3 months, debanding and full correction was achieved in
      43% (n = 62). In addition to the 29% (n = 42) that were confirmed to be dead, an
      additional 28% (n = 39) were not corrected and of these almost half were regarded
      as lost to follow-up. Thus, of the entire cohort of patients, 57% (n = 81) have
      not achieved definitive correction at the termination of data collection.
      CONCLUSION: A strategy of deferring biventricular repair by the application of a
      pulmonary artery band is ineffective under Third World conditions largely due to
      lack of patient compliance. This study shows that the overall mortality in the
      inter-stage period following PAB is high prior to definitive correction. Less
      than half of patients will eventually be repaired in a reasonable time frame and
      patient follow-up is unreliable. We conclude that consideration should be given
      to early definitive repair even in perceived high-risk cases.

PMID- 21733710
TI  - Multimodality imaging of caseous calcification of mitral annulus.

PMID- 21733711
TI  - Partial anomalous pulmonary venous connection to the superior vena cava: the
      outcome after the Warden procedure.
AB  - OBJECTIVE: Partial anomalous pulmonary venous connection (PAPVC) draining into
      the superior vena cava (SVC) has been repaired with various techniques. We
      investigated the outcome of the Warden procedure for repair of this anomaly.
      METHODS: From December 1994 to January 2011, 30 patients underwent a Warden
      procedure for repair of PAPVC to the SVC in our center. Their median age at the
      time of the operation was 4.9 years (range, 1 month to 55 years). Follow-up data
      were obtained through a review of medical records, correspondence with the
      patients' cardiologists, and direct telephone contact. The mean follow-up
      duration was 5.3 +/- 5.1 years (range, 1 month to 16 years). RESULTS: One patient
      died of an underlying cardiac condition and cerebral complication unrelated to
      the Warden procedure. One patient had transient postoperative sinus node
      dysfunction. During follow-up, pulmonary venous pathway obstruction occurred in
      one patient, and systemic venous pathway obstruction occurred in three patients.
      Re-operation or re-intervention for systemic venous pathway obstruction was
      required in younger (<2 years) and smaller (<7 kg) patients within 1 year after
      the Warden procedure. All patients were in regular sinus rhythm in the latest
      electrocardiogram. CONCLUSIONS: The Warden procedure is a safe and effective
      surgical option for repair of PAPVC to the SVC in terms of preserving the sinus
      node function and non-obstructive pulmonary venous pathway. However, more
      attention must be paid to the reconstruction of non-obstructive systemic venous
      pathway, especially in younger and smaller children. Patch augmentation could be
      considered and effectively performed, if there is any doubt regarding tension
      free anastomosis.

PMID- 21733712
TI  - Left coronary to pulmonary artery fistula in a patient with severe coronary
      atherosclerosis.

PMID- 21733713
TI  - The philosophy of a nerve-sparing thoracotomy closure.

PMID- 21733714
TI  - Long-term health-related quality of life following surgery for lung cancer.
AB  - OBJECTIVE: The aim of the study was to examine the long-term health-related
      quality of life following surgery for lung cancer. METHODS: We performed a
      prospective population-based cohort study to explore health-related quality of
      life after lung surgery. We used a validated quality-of-life instrument (Short
      Form-36 (SF-36)) to gather information on health-related quality of life at
      baseline, 6 months, and 2 years after surgery. The main outcome measures were the
      SF-36 physical component summary (PCS) and mental component summary (MCS) scores.
      RESULTS: Between 2006 and 2008, 249 patients were included. The response rate at
      6 months was 85% and, at 2 years of follow-up, was 95%. The study population
      consisted of 166 patients who completed all three SF-36 questionnaires. The PCS
      score decreased from baseline to 6 months (47.4 vs 41.1; p < 0.001) and remained
      unchanged at the 2-year follow-up (41.1 vs 41.4). The MCS score increased from
      baseline to 6 months (40.5 vs 44.6; p = 0.001), with a further improvement at 2
      years (44.6 vs 46.9; p = 0.005). At 2-year follow-up, both the PCS score and the
      MCS score of the study population were lower than that of an age- and gender
      matched reference population (41.4 vs 44.0; p = 0.013 and 46.9 vs 50.6; p =
      0.01). CONCLUSIONS: We found that patients undergoing surgery for lung cancer had
      an early decrease in the physical aspect of health-related quality of life at 6
      months after surgery, which was still present at 2 years of follow-up. A moderate
      clinically relevant improvement was noted in the mental aspect at 6 months and
      further improvement was reported at 2 years of follow-up.

PMID- 21733715
TI  - Combination or sequencing strategies to improve the outcome of metastatic renal
      cell carcinoma patients: a critical review.
AB  - The introduction of novel anti-angiogenic therapies has greatly improved the
      outcome of patients with metastatic renal cell carcinoma (mRCC). The use of these
      therapies in combination or sequentially is proposed to provide greater efficacy.
      We have reviewed completed and ongoing clinical trials in mRCC that have reported
      efficacy and/or safety data of novel therapies used in combination or
      sequentially. Bevacizumab appears to be a useful partner when combined with
      interferon (IFN), while controversial results have been reported when combined
      with temsirolimus and everolimus. Other combinations appear to have unacceptable
      tolerability or require dose or schedule optimization. Sequencing data provide a
      clear indication that multiple lines of treatment may extend survival. The
      'ideal' sequence, however, is still unknown. In conclusion, novel therapies used
      in combination or sequentially have potential to provide optimised treatment and
      patient outcomes in mRCC. The results from ongoing/planned trials are expected to
      help shape future therapy.

PMID- 21733716
TI  - MKP-1 regulates cytokine mRNA stability through selectively modulation
      subcellular translocation of AUF1.
AB  - MAPK phosphatase-1 (MKP-1)/dual specificity protein phosphatase-1 (DUSP-1) is a
      negative regulator of the host inflammatory response to infection. However, the
      mechanisms underlying the regulation of cytokine expression by MKP-1, especially
      at the post-transcriptional level, have not been fully delineated. In the current
      study, MKP-1 specifically dephosphorylated activated MAPK responses and
      attenuated LPS-induced IL-6, IL-10, and TNF-alpha expression. In addition, MKP-1
      was important in destabilizing cytokine mRNAs. In LPS-stimulated rat macrophages
      with overexpressed MKP-1, half-lives of IL-6, IL-10 and TNF-alpha mRNAs were
      significantly reduced compared to controls. Conversely, half-lives of IL-6, IL
      10, and TNF-alpha mRNAs were significantly increased in bone marrow macrophages
      derived from MKP-1 knock out (KO) mice compared with macrophages derived from MKP
      1 wild type (WT) mice. Furthermore, MKP-1 promoted translocation of RNA-binding
      protein (RNA-BP) ARE/poly-(U) binding degradation factor 1 (AUF1) from the
      nucleus to the cytoplasm in response to LPS stimulation as evidenced by Western
      blot and immunofluorescent staining. Knockdown AUF1 mRNA expression by AUF1 siRNA
      in MKP-1 WT bone marrow macrophages significantly delayed degradation of IL-6, IL
      10 and TNF- alpha mRNAs compared with controls. Finally, AUF1 was
      immunoprecipitated with the RNA complex in cellular lysates derived from bone
      marrow macrophages of MKP-1 KO vs. WT mice, which had increased AUF1-bound target
      mRNAs, including IL-6, IL-10, and TNF-alpha in WT macrophages compared with MKP-1
      KO macrophages. Thus, this work provides new mechanistic insight of MKP-1
      signaling and regulation of cytokine mRNA stability through RNA binding proteins
      in response to inflammatory stimuli.

PMID- 21733717
TI  - Leptin and resistin induce increased procoagulability in diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) suffer from an increased risk of
      cardiovascular events caused by thrombotic conditions. Adipose tissue might play
      a crucial role in this pathogenesis by synthesis of procoagulant mediators. This
      study was performed to elucidate the role of the adipocytokines leptin and
      resistin in the development of hypercoagulability and hypofibrinolysis under
      diabetic conditions. METHODS: Sixty two patients with or without DM were included
      in our study to measure leptin, resistin and tissue factor (TF) plasma
      concentrations. Moreover, flow chamber experiments were performed to assess
      factor Xa and plasmin activity on the surface of HUVECs. Western blot and real
      time PCR were performed to determine mRNA and protein expression of main factors
      of the coagulation and fibrinolytic system. RESULTS: Patients with diabetes
      showed increased levels of leptin and resistin (leptin: 25.69+/-13.9 vs. 15.98+/
      17.5 ng/mL, p<0.05; resistin: 2.61+/-0.6 vs. 1.19+/-0.7 ng/mL, p<0.05), which
      were positively correlated with TF. In vitro, leptin and resistin induced
      increased factor Xa activity (leptin: 4.29+/-0.57-fold, p<0.05; resistin 4.19+/
      0.7-fold, p<0.05 vs. control) on HUVECs as also reflected by elevated TF mRNA and
      protein expression. Moreover, stimulatory (plasminogen activator inhibitor 1) and
      inhibitory (tissue plasminogen activator) mediators of the fibrinolytic cascade
      were induced by leptin and resistin, leading to a balanced plasmin activity
      regulation. CONCLUSIONS: Leptin and resistin lead to a procoagulant state in
      HUVECs by inducing TF expression. This mechanism might be one explanation for the
      prothrombotic state observed under diabetic conditions.

PMID- 21733718
TI  - Development of a sandwich ELISA for evaluating soluble PD-L1 (CD274) in human
      sera of different ages as well as supernatants of PD-L1+ cell lines.
AB  - PD-L1 (CD274) is a critical membrane-bound costimulatory molecule that inhibits
      immune responses through its receptor, PD-1. Previous data have showed that this
      molecule is associated with autoimmune diseases, chronic viral infections and
      tumor immune escape. However, the existence and role of soluble form of human PD
      L1 (sPD-L1) remain unknown. We show here that a novel enzyme-linked immunosorbent
      assay (ELISA) was developed to detect the sPD-L1 protein. Many culture
      supernatants of the PD-L1+ cell lines contain high levels of this factor.
      Interestingly, the sPD-L1 is detectable in human serum and the concentration
      increases in an age-dependent manner. Human sPD-L1 has a unique protein form in
      the serum and the matrix metalloproteinase inhibitor (MMPI) could suppress sPD-L1
      production. Moreover, the sPD-L1 could specially bind to PD-1. Together, these
      data demonstrate that the existence of circulating sPD-L1 in human serum might
      play an important role in immunoregulation.

PMID- 21733719
TI  - Regulatory T cell lineage commitment in the thymus.
AB  - A substantial fraction of the Foxp3(+) CD4(+) regulatory T (T(reg)) cell
      repertoire is generated through instructive and/or selective processes in the
      thymus, and there is some consensus that clonal deviation into the T(reg) lineage
      is a result of self-antigen recognition. Paradoxically, the same holds true for a
      diametrically different cell fate decision of developing thymocytes, namely their
      removal from the repertoire through apoptotic cell death (clonal deletion). Here,
      we will review our current understanding of how T cell receptor stimulation,
      cytokine signaling, co-stimulation, epigenetic modifications and T cell intrinsic
      developmental tuning synergize during T(reg) cell differentiation, and how
      instructive signals converge at the Foxp3 gene-locus during entry into the T(reg)
      cell lineage. We will also discuss how these parameters relate to known
      determinants of negative selection.

PMID- 21733720
TI  - Navigating the poststroke continuum of care.
AB  - Stroke is a significant source of death and disability worldwide. The increasing
      prevalence of stroke survivors forecasts substantial socioeconomic burden and a
      greater need for comprehensive poststroke rehabilitative services. Despite the
      rapidly rising burden of cerebrovascular disease, particularly in developing
      countries, there has been limited implementation of multidisciplinary stroke
      units, a proven care modality in reducing patient mortality and improving
      functional outcomes. Transitioning from these acute inpatient settings to in- and
      outpatient rehabilitation or long-term care environments has consistently been
      identified as an obstacle to quality stroke rehabilitation. To address the
      barriers preventing the seamless delivery of poststroke care, an evaluation of
      patient-caregiver perspectives, treatment challenges, and system-wide
      shortcomings is presented. The fragmentation of the current poststroke chain of
      care could benefit from the introduction of case managers or "navigators,"
      discharge planning, electronic medical records, and evidence-based
      neurorehabilitation guidelines. By aiding in successful care transitions, these
      proposed efforts could advance post-acute stroke patients along the care
      continuum to achieve their rehabilitative goals.

PMID- 21733721
TI  - Risk of stroke in 28,000 patients with celiac disease: a nationwide cohort study
      in Sweden.
AB  - BACKGROUND: Earlier studies on stroke in celiac disease (CD) have been
      underpowered, but a recent study suggested that childhood CD is associated with a
      10-fold increased risk of death from stroke, although it was based on small
      numbers. We examined the risk of stroke in patients with biopsy-verified CD.
      METHODS: We collected biopsy data from all 28 pathology departments in Sweden and
      identified 28,676 individuals with CD diagnosed between 1969 and 2007 (Marsh 3:
      villous atrophy). In the main analyses, we used Cox regression to estimate hazard
      ratios (HRs) for stroke in patients with CD compared with HRs for stroke in
      141,806 sex- and age-matched controls. RESULTS: During follow-up, there were 785
      first-stroke diagnoses in patients with CD and 2937 in reference individuals.
      Patients with CD were at increased risk of stroke (HR 1.10; 95% confidence
      interval [CI] 1.01-1.19). HRs were similar for ischemic stroke and brain
      hemorrhage and were not affected by adjustment for type 1 diabetes, rheumatoid
      arthritis, use of medication against hypertension, or dyslipidemia. The absolute
      risk of stroke in patients with CD was 267 per 100,000 person-years (excess risk
      24/100,000). The highest risk estimates occurred in the first year, with
      virtually no increased risk after more than 5 years of follow-up after CD
      diagnosis. The HR for stroke in childhood CD was 1.10 (95% CI 0.37-3.22).
      CONCLUSIONS: Patients with CD are at only a small increased risk of stroke, which
      persists only for a brief period after diagnosis. CD does not seem to be a major
      risk factor for stroke.

PMID- 21733722
TI  - Restless legs syndrome and conditions associated with metabolic dysregulation,
      sympathoadrenal dysfunction, and cardiovascular disease risk: a systematic
      review.
AB  - Restless legs syndrome (RLS) is a distressing sleep and sensorimotor disorder
      that affects a large percentage of adults in the western industrialized world and
      is associated with profound reductions in quality of life. However, the etiology
      of RLS remains incompletely understood. Enhanced understanding regarding both the
      antecedents and sequelae of RLS could shed new light on the pathogenesis of RLS.
      Evidence from an emerging body of literature suggests associations between RLS
      and diabetes, hypertension, obesity, and related conditions linked to sympathetic
      activation and metabolic dysregulation, raising the possibility that these
      factors may likewise play a significant role in the development and progression
      of RLS, and could help explain the recently documented associations between RLS
      and subsequent cardiovascular disease. However, the relation between RLS and
      these chronic conditions has received relatively little attention to date,
      although potential implications for the pathogenesis and treatment of RLS could
      be considerable. In this paper, we systematically review the recently published
      literature regarding the association of RLS to cardiovascular disease and related
      risk factors characterized by sympathoadrenal and metabolic dysregulation,
      discuss potential underlying mechanisms, and outline some possible directions for
      future research.

PMID- 21733723
TI  - Quantitative assessment of physiological and behavioural parameters in healthy
      dairy cows evoked by transcutaneous electrical nerve stimulation of the udder.
AB  - The pain and distress associated with transcutaneous electrical nerve stimulation
      (TENS) of the udder was evaluated by treating 20 healthy dairy cows with an
      electrical udder stimulator. This generated a sequence of pulses (frequency:
      160+/-10% impulses per second, duration 250 MUs) and provided voltage ranges from
      0 to 10 volts (+/-10%). Trials took place on three consecutive days, twice daily
      after morning and evening milking. Daily sessions were divided into two periods:
      (1) control (sham treatment) and (2) treatment (real treatment). Physiological
      (heart rate, respiratory rate, and plasma cortisol concentration) as well as
      ethological parameters (kicking, weight shifting, and looking backwards to udder)
      were defined as pain-indicating parameters and observed. Evaluation of data
      showed that only one parameter (kicking) was significantly increased during real
      treatment compared to sham treatment. It is concluded that the TENS therapy
      tested in this study can evoke changes in behaviour (increased kicking)
      consistent with an experience of pain in some cows.

PMID- 21733724
TI  - Long-term follow-up in two siblings with pyridoxine-dependent seizures associated
      with a novel ALDH7A1 mutation.
AB  - Pyridoxine-dependent seizures (PDS) is a rare disorder characterized by seizures
      resistant to anticonvulsants but controlled by daily pharmacologic doses of
      pyridoxine. Mutations in the antiquitin (ALDH7A1) gene have recently reported to
      cause PDS in most of patients. We report the long-term follow-up in two PDS
      siblings carrying a novel ALDH7A1 mutation.

PMID- 21733725
TI  - [Care for a family carer in Primary Care using the uncertainty theory].
AB  - This case discussion starts from the Uncertainty Theory of illness of Merle
      Mishel, who raised the idea that even without a solution to the uncertainty, a
      person should accept it as a part of their life and reinterpret it as an
      opportunity to promote a new view of life governed by probability. The author
      proposes theoretical concepts that allow the phenomena experienced by family
      caregivers to be approached from the perspective of their experiences and stress.
      It establishes uncertainty and indecisiveness as contradictions that should not
      create anxiety permanently. This can be released gradually, if we create lines of
      flight though the care. Among these lines are located the Problem Solving Method
      as a strategy useful in primary health care to reduce the uncertainty of the
      caregivers. This article describes the outcome of Isabel, a 63- year-old female
      family caregiver of her dependent mother and her daughter with anorexia. The
      primary care nurse identifies the problem of weariness of the care-givers role
      and that of conflict of decisions during home visits. It describes the assessment
      made from the main concepts of the theory and the work with the care-givers by
      the problem solving method in order to reduce anxiety and help to mobilize
      internal resources and increase their welfare.

PMID- 21733726
TI  - [Analysis of Satisfaction in women with recent diagnosis of breast cancer.
      Multicenter study in Oncology Services].
AB  - OBJECTIVES: 1) Evaluation of the level of satisfaction on the care received in
      women diagnosed with breast cancer and identifying improvement areas, 2)
      Comparison of proportions of patients satisfied and dissatisfied with the
      attention received in the Oncology Services (OS) in Asturias (Spain). METHODS:
      Multicenter, cross-sectional comparative study using an anonymous and voluntary
      satisfaction survey. The studied population was composed of women diagnosed with
      breast cancer in 2008, and receiving care in OS in Asturias. The tool used was
      the modified SERVQHOS, adapted to our context. Analysis was performed to
      determine Cronbach's alpha reliability of the instrument after the adjustments;
      descriptive statistics and Pearson chi-square test were carried out in the
      comparisons of satisfaction in the different OS, assuming a confidence level of
      95%. The SPSS 18.0 statistics package was used. RESULTS: A total of 85 patients
      the OS A, 107 from the OS B and 34 from the OS C participated. The information
      provided by doctors was the only aspect of the objective quality with which
      participants of the OS A were satisfied. Significant differences were found
      between departments regarding the status of the clinics (P<.00) and waiting times
      (P<.00). All the participants were satisfied with the kindness of the staff, but
      the highest proportion of dissatisfied was in OS B (P<.00). Communication with
      family members did not reach participants' expectations in OS C (P=.02).
      CONCLUSIONS: Our findings have identified improvement opportunities in several
      aspects of care in our OS. From them, aspects evaluated as positive might be
      promoted, while corrective actions might be established for the negative ones,
      all of them aimed to improve the quality of care in OS in Asturias.

PMID- 21733727
TI  - A double-blind study of the efficacy and safety of multiple daily doses of
      amikacin versus one daily dose for children with perforated appendicitis in Costa
      Rica.
AB  - BACKGROUND: There is evidence that aminoglycosides given in a single daily dose
      (once daily dose, ODD) are as effective and safe as multiple daily doses (MDD).
      However, the published pharmacokinetic and pharmacodynamic data are overly
      representative of pediatric populations in Europe and the USA, and not
      representative of low or middle-income countries such as Costa Rica, in which the
      patient population might differ from those in higher income settings. METHODS: A
      double-blind, randomized clinical trial of the efficacy and safety of ODD vs. MDD
      amikacin therapy was conducted for children aged 2-12 years with an
      intraoperative diagnosis of perforated appendicitis. One hundred patients were
      randomized following a one-to-one randomization to receive either amikacin 7.5
      mg/kg every 8 h (MDD) or 22.5 mg/kg as a single dose (ODD). Patients in both
      groups were given clindamycin 10 mg/kg every 6 h. Efficacy was evaluated by the
      occurrence of intra-abdominal abscesses, documented by abdominal ultrasound, and
      therapeutic failure. Safety was determined by the presence of renal or cochlear
      toxicity. RESULTS: Fifty patients were enrolled in each group. There were no
      statistically significant differences in the incidence of intra-abdominal
      abscesses or therapeutic failures, or in the occurrence of cochlear or renal
      toxicity, between the MDD and ODD treatment groups. CONCLUSIONS: In this patient
      population of Costa Rican children with perforated appendicitis, we found that
      amikacin ODD is as safe and effective as the MDD regimen. This could have
      implications for national health systems such as that in Costa Rica, as ODD is
      presumably a more economic option and may reduce the cost of antibiotic treatment
      in patients with perforated appendicitis. This would need to be confirmed through
      an economic analysis, which is outside the purview of this paper.

PMID- 21733728
TI  - Misleading abstract conclusions in randomized controlled trials in rheumatology:
      comparison of the abstract conclusions and the results section.
AB  - INTRODUCTION: Readers of scientific articles often read only the abstract and its
      conclusions because of lack of time or of access to the full-length articles.
      OBJECTIVES: To assess the prevalence of misleading conclusions in abstracts of
      randomized controlled trials (RCTs) in rheumatology, determine whether trials are
      registered and whether abstract conclusions are based on the primary outcome
      (PO), and identify the predictors of misleading abstract conclusions. METHODS: We
      searched Medline, Embase and the Cochrane Collaboration for reports of RCTs
      assessing rheumatoid arthritis, osteoarthritis or spondylarthropathies published
      between January 2006 and April 2008. Abstract conclusions were misleading if: the
      PO was not reported in the conclusion; the conclusions were based on only a
      secondary outcome or subgroup results; the results and conclusions were in
      disagreement; negative results were suggested as equivalent, or if there was no
      discussion of benefits and risks in cases of serious adverse events. RESULTS: Of
      the 144 reports selected, we focused on the 105 articles containing a clear PO.
      Twenty-four reports (23%) contained misleading conclusions. Lack of PO reporting
      (n=10) and conclusions disagreeing with article results (n=7) were the most
      frequent reasons. Nineteen out of 144 (13.2%) declared study registration with
      clear and similar registered and published POs and no misleading abstract
      conclusions. Reports of negative results showed a higher frequency of misleading
      conclusions as did those assessing osteoarthritis. On multivariable analysis,
      only negative results predicted misleading abstract conclusions (OR=9.58 [3.20
      28.70]). CONCLUSIONS: Almost one-quarter of these RCT in rheumatology had
      misleading conclusions in the abstract, especially those with negative results.

PMID- 21733729
TI  - Bone loss in adults with cystic fibrosis: prevalence, associated factors, and
      usefulness of biological markers.
AB  - BACKGROUND: Osteoporosis is a common complication of cystic fibrosis. OBJECTIVE:
      To determine the prevalence of osteopenia and osteoporosis in adults with cystic
      fibrosis and to look for factors associated with low bone mineral density (BMD)
      values. METHODS: During this prospective 2-year study, we collected clinical data
      (history, body mass index, and treatments) and laboratory data (nutritional and
      hormonal status, markers for inflammation and bone turnover, and calcium and
      phosphate levels). Lung function tests and a 6-meter walking test were performed.
      BMD was measured at the spine, total hip, and femoral neck. RESULTS: We included
      55 patients (31 women) with a mean age of 31.9 years; 14 were homozygous and 25
      heterozygous for the deltaF508 mutation and 20 (36%) had a history of fractures.
      BMD values indicated osteopenia in 32 (58.2%) patients and osteoporosis in 11
      (20%) patients at one or more measurement sites. At all three sites, BMD values
      correlated with the body mass index, forced vital capacity as % predicted, and
      forced expiratory volume in 1 s as % predicted; at the femoral neck and total
      hip, BMD values correlated with the 6-meter walking test result and grip
      strength. CONCLUSION: BMD was low in 78.2% of adults with cystic fibrosis. Three
      factors reflecting lung disease severity were associated with low BMD values,
      namely, respiratory function, physical function (walking test and grip strength),
      and nutritional status.

PMID- 21733730
TI  - Associations of HLA-shared epitope, anti-citrullinated peptide antibodies and
      lifestyle-related factors in Hungarian patients with rheumatoid arthritis: data
      from the first Central-Eastern European cohort.

PMID- 21733731
TI  - Usefulness of routine hepatitis C and hepatitis B serology in the diagnosis of
      recent-onset arthritis. Systematic prospective screening in all patients seen by
      the rheumatologists of a defined area--brief report.
AB  - OBJECTIVE: Previous studies evaluating the usefulness of systematic screening for
      hepatitis B and C in patients with recent-onset arthritis suffered from a major
      bias since they were conducted in hospitals. The objective of the present study
      was to evaluate the relevance of such screening, performed by hospital and office
      based rheumatologists of a defined area, in the diagnosis of arthritis or
      inflammatory polyarthralgia of less than 1 year duration. METHODS: The CRRRI is a
      network which includes most hospital and office-based rheumatologists of an area
      with a population of 506,755 inhabitants. All patients seen by the CRRRI
      participants in their usual practice between March 2008 and December 2010 for
      inflammatory polyarthralgia, mono-, oligo-, or polyarthritis of less than 1 year
      duration were included. Patients' serum samples were screened for the presence of
      anti-hepatitis C virus (HCV) antibodies, with positive samples further evaluated
      for HCV-RNA with a reverse transcriptase-polymerase chain reaction, and for the
      presence of hepatitis B virus (HBV) infection. RESULTS: Two hundred and thirty
      three patients were included (162 women, 71 men; mean age of 50.6+/-15.8 years).
      Patients were evaluated for inflammatory polyarthralgia (n=51), monoarthritis
      (n=21), oligoarthritis (n=35) or polyarthritis (n=126) lasting for a mean 19.8+/
      29.8 weeks. No new HCV or HBV infection diagnosis was done. CONCLUSION: In this
      study not suffering from a hospital-selection bias, screening for hepatitis C and
      B infection was not helpful in the diagnosis process of recent-onset arthritis.
      KEY MESSAGES: Systematic hepatitis B and C serology is not relevant in patients
      with recent-onset (<1 year) arthritis.

PMID- 21733732
TI  - Associated risk factors with worse functional prognosis and hip replacement
      surgery in ankylosing spondylitis.

PMID- 21733733
TI  - Elevated BAFF (BLyS) and APRIL in Juvenile idiopathic arthritis patients:
      relation to clinical manifestations and disease activity.
AB  - OBJECTIVE: To assess the level of B-cell activating factor belonging to the tumor
      necrosis factor family (BAFF) also known as B-lymphocyte stimulator (BLyS) and A
      proliferation-inducing ligand (APRIL) in the serum of Juvenile idiopathic
      arthritis (JIA) patients and to detect their relation to the clinical
      manifestations and disease activity in the different subtypes of the disease.
      METHODS: Seventy-four consecutively recruited JIA patients were clinically
      examined, the Juvenile arthritis disease activity score in 27 joints (JADAS-27)
      calculated and Childhood Health Assessment Questionnaire (CHAQ) used to measure
      the functional status. Thirty-four healthy matched children served as controls.
      Routine laboratory examinations were recorded and serum BAFF and April were
      determined. RESULTS: The JIA patients were 20 systemic-onset, 31 oligoarticular
      and 23 polyarticular. Serum BAFF and APRIL were elevated in JIA patients being
      higher in systemic onset and both significantly correlated. APRIL significantly
      correlated with both JADAS-27 and CHAQ scores while BAFF correlated only with
      JADAS-27. The APRIL serum levels were significantly associated with the presence
      of RF and ANA. The BAFF serum levels were significantly higher in oligoarticular
      onset JIA patients with uveitis compared to those without. CONCLUSION: Our
      results suggest increased BAFF and APRIL serum levels in JIA patients denoting
      their possible role in the disease and calling for additional research to
      elucidate the intrinsic mechanisms explaining APRIL and BAFF over expression.

PMID- 21733734
TI  - Septic arthritis with negative bacteriological findings in adult native joints: a
      retrospective study of 74 cases.
AB  - BACKGROUND: No microorganism is identified in 7-35% of cases of septic arthritis.
      The diagnosis is, therefore, only presumptive. We reviewed our cases of septic
      arthritis in adult native joints to determine the frequency of negative cultures,
      disease characteristics and the frequency of misdiagnosis of septic arthritis.
      METHODS: This retrospective study included all patients admitted to our
      department from 1979-2005 with arthritis, diagnosed and treated as septic.
      RESULTS: No microorganism was isolated from synovial fluid or blood samples from
      74 out of 398 (19%) patients with presumed septic arthritis. Patients without
      microorganisms were younger (54 vs 62 years), less likely to have risk factors
      for septic arthritis (31% vs 41%) and had lower mortality (0 vs 5%) than patients
      with positive cultures. Long-term outcome was known for 48 patients. A
      retrospective analysis of all data and long-term outcome concluded that septic
      arthritis was probable in 18 patients and improbable in 13. Ten of the latter
      developed rheumatic disease after a mean time of 6 months: rheumatoid arthritis
      (n=3), spondyloarthropathies (n=3), unclassified rheumatic disease (n=2), Wegener
      granulomatosis (n=1) and cytosteatonecrosis (n=1). Fever and signs of
      inflammation were more frequent and synovial fluid cell counts were higher in
      patients with improbable septic arthritis. Conversely, radiological signs were
      more common in patients with probable septic arthritis. CONCLUSION: At least 14%
      of patients diagnosed with septic arthritis with negative bacteriological results
      subsequently develop rheumatic disease. This pseudoseptic arthritis is
      indistinguishable from true septic arthritis. When no microorganism is
      identified, the diagnosis remains presumptive and follow-up is necessary to
      screen for other diseases, especially rheumatic diseases.

PMID- 21733735
TI  - Occupational exposure in parkinsonian disorders: a 43-year prospective cohort
      study in men.
AB  - BACKGROUND: Several occupations and occupational exposures have been investigated
      for associations with Parkinson's disease. Common findings are increased risk
      associated with pesticide exposure and no association between Parkinson's disease
      and welding. METHODS: We explored the association between a broad range of
      possible occupational risk factors and Parkinson's disease as well as Parkinson's
      disease plus other forms of Parkinsonism (referred to as Parkinsonian disorders),
      using prospectively collected data in the population-based Swedish Twin Registry.
      A cohort of 14,169 Swedish men was followed for up to 43 years. We identified 234
      Parkinsonian disorder cases including 204 Parkinson's disease cases with complete
      data. We assessed exposure to 14 chemical and biological compounds through a job
      exposure matrix. Hazard ratios (HR) with 95% confidence intervals (CI) adjusted
      for age, smoking, and education were used to estimate the relative risk of
      disease associated with exposure. RESULTS: Exposure to inorganic dust was
      associated with increased risk of Parkinson's disease and Parkinsonian disorders,
      HR 1.6 (95% CI 1.1-2.4) and 1.5 (1.0-2.2) respectively. There was no association
      between Parkinson's disease or Parkinsonian disorders and occupational exposure
      to pesticides, welding smoke, metal dust, wood dust, animal handling, stone and
      concrete dust, chrome and nickel dust, quartz dust, organic dust, oil, asbestos,
      organic solvents and irritating gas. CONCLUSIONS: Inorganic dust should be
      explored further as a potential risk factor for Parkinson's disease. Occupational
      exposure to pesticides and twelve other compounds explored in this study may not
      be associated with risk of Parkinson's disease in Swedish men.

PMID- 21733736
TI  - Co-existence of primary hyperparathyroidism and Parkinson's disease in three
      patients: an incidental finding?

PMID- 21733737
TI  - Tardive syndrome and Parkinson's disease responsive to concomitant tetrabenazine
      and levodopa therapy.

PMID- 21733738
TI  - A case of parkinsonism and dopa-induced severe dyskinesia associated with novel
      mutation in the GTP cyclohydrolase I gene.

PMID- 21733739
TI  - Increased levels of total tau protein in the cerebrospinal fluid in Huntington's
      disease.

PMID- 21733740
TI  - Role of voriconazole in combined acanthamoeba and fungal corneal ulcer.
AB  - We report a case of a 21 year old male who presented with smear-proven fungal
      corneal ulcer in left eye, refractory to treatment with topical natamycin.
      Corneal smears and culture were taken along with anterior chamber tap for
      microbiological investigations and intracameral 1% voriconazole was injected
      followed by institution of oral as well as topical voriconazole drops. Corneal
      and aqueous smear as well as culture confirmed the presence of acanthamoeba. The
      keratitis responded favourably to voriconazole therapy which was instituted along
      with topical trophicidal drugs and anterior chamber became quiet by 7th day. The
      patient was slowly tapered from voriconazole and was off the drug by 6 months. At
      one year follow up, he continues to remain asymptomatic. The possibility exists
      that the fungal organisms had either partially or completely responded to
      natamycin eye drops and voriconazole therapy further inhibited their growth along
      with being highly efficacious in suppressing acanthamoeba trophozoites.
      Voriconazole may be specifically instrumental in corneal ulcers with coinfection
      of acanthamoeba and fungal organisms and preventing recrudescence of both. Normal
      saline wet mount and 10% KOH mount of paracentesis sample for suspicious cases of
      refractory corneal ulcers to specifically look for trophozoites in order to
      institute timely treatment are recommended.

PMID- 21733741
TI  - Re-feeding syndrome in head and neck--prevention and management.
AB  - "Re-feeding syndrome" is a potentially fatal, but entirely avoidable condition.
      It was first reported in severely malnourished prisoners in World War II.
      Recently interest in the topic has seen a resurgence with the increased use of
      artificial nutrition and improved monitoring. In 2007, the National Institute for
      Clinical Excellence (NICE) has produced guidelines for the prevention and
      management of re-feeding syndrome. These have some important differences to the
      previous guidelines of the Parenteral and Enteral Nutrition Group of the British
      Dietetic Association (PENG). The aim of this article is to review the literature
      on re-feeding syndrome, and present the most recent guidelines for its diagnosis,
      prevention and treatment.

PMID- 21733742
TI  - A prospective randomized multicenter clinical trial of the Provox2 and Groningen
      Ultra Low Resistance voice prostheses in the rehabilitation of post-laryngectomy
      patients: a lifetime and preference study.
AB  - To prospectively study patients' preference for and the lifetime of the Groningen
      Ultra Low Resistance (GULR) and Provox2 tracheo-esophageal shunt prosthesis
      (TESP, plural TESPs) in post-laryngectomy patients. Eighty post-laryngectomy
      patients were included in 4 oncological centers in the Netherlands. We used a
      repeated measures design study with 4 randomized groups in a partial cross-over
      design using 3 consecutive TESPs (3 intervals) in different orders. (Group 1:
      GULR-GULR-GULR; Group 2: GULR-GULR-Provox2; Group 3: Provox2-Provox2-GULR; and
      Group 4: Provox2- Provox2-Provox2). Replacement dates and reasons for replacement
      were monitored with questionnaires as were patients' preferences for GULR or
      Provox2. A great variability of lifetime within and between groups was seen. Mean
      lifetimes found (all groups and intervals added) were 106.2 and 102.7 days, and
      median lifetimes were 76 and 65 days for GULR and Provox2, respectively. Lifetime
      showed no significant differences between groups, intervals, and TESP types. Many
      patients dropped out due to reasons having to do with GULR-characteristics
      (n=21). The main dropout reason was "high phonating resistance (HPR)" (57.1%).
      Only 10 patients preferred GULR. A significantly larger number of patients (n=39,
      79.6%) preferred Provox2 either by choice or by dropping out due to GULR
      characteristics (P<0.001). The main replacement reasons were "leakage though
      TESP" (GULR 59.1%, Provox2 52.1%) and HPR (GULR 15.9%, Provox2 12.7%). No
      significant differences in lifetime between GULR and Provox2 were found. The
      patients' preference for Provox2 was significant (P<0.001). Patients' preference
      was a more important outcome measurement in TESP effectiveness than device
      lifetime.

PMID- 21733743
TI  - Phytochrome structure and photochemistry: recent advances toward a complete
      molecular picture.
AB  - Phytochromes are nature's primary photoreceptors dedicated to detecting the red
      and far-red regions of the visible light spectrum, a region also essential for
      photosynthesis and thus crucial to the survival of plants and other
      photosynthetic organisms. Given their roles in measuring competition and
      diurnal/seasonal light fluctuations, understanding how phytochromes work at the
      molecular level would greatly aid in engineering crop plants better suited to
      specific agricultural settings. Recently, scientists have determined the three
      dimensional structures of prokaryotic phytochromes, which now provide clues as to
      how these modular photoreceptors might work at the atomic level. The models point
      toward a largely unifying mechanism whereby novel knot, hairpin, and dimeric
      interfaces transduce photoreversible bilin isomerization into protein
      conformational changes that alter signal output.

PMID- 21733744
TI  - Synthesis, spectroscopic and thermal studies of some IIB group complexes with a
      new N2-Schiff base ligand.
AB  - Synthesis, spectroscopic and thermal studies of some complexes of a new N(2)
      Schiff base ligand of N(1),N(2)-bis((E)-2-methyl-3-phenylallylidene)ethane-1,2
      diamine (L) with a general formula of MLX(2) (M = Zn(II), Cd(II) and Hg(II); X =
      Cl(-), Br(-), I(-), SCN(-) and N(3)(-)) are described. The ligand and its
      complexes were characterized by elemental analysis, molar conductance, UV-vis
      spectra, FT-IR spectra, MS, (1)H NMR and (13)C NMR spectra. The conductivity
      measurement as well as spectral data indicated that the complexes are non
      electrolyte. (1)H and (13)C NMR spectra have been studied in DMSO-d(6) and/or
      CDCl(3). The thermal behavior of the complexes shows weight loss by decomposition
      of the anions and ligand segments in the subsequent steps. Activation
      thermodynamic parameters of decomposition such as E*, DeltaH*, DeltaS* and
      DeltaG* were calculated from TG curves.

PMID- 21733745
TI  - Molecular interaction study of the diisopropyl ether-propionic acid mixture by
      spectroscopic and dielectric studies.
AB  - FTIR and 13C NMR spectral studies have been carried out on diisopropyl ether
      propionic acid binary mixture to probe the molecular interactions and
      stoichiometry of complexation. Density functional theory (DFT) calculations of
      vibrational frequencies of pure acid and ether-acid binary mixtures have also
      been performed. In addition, Kirkwood-correlation factors, excess permittivity
      and excess free energy of mixing have been obtained at various concentrations and
      at four different temperatures from the dielectric measurements. Excess
      permittivity is found to have positive deviation and excess free energy deviates
      negatively from ideal behaviour.

PMID- 21733746
TI  - The mixed anion mineral parnauite Cu9[(OH)10|SO4|(AsO4)2].7H2O--a Raman
      spectroscopic study.
AB  - The mixed anion mineral parnauite Cu(9)[(OH)(10)|SO(4)|(AsO(4))(2)].7H(2)O from
      two localities namely Cap Garonne Mine, Le Pradet, France and Majuba Hill mine,
      Pershing County, Nevada, USA has been studied by Raman spectroscopy. The Raman
      spectrum of the French sample is dominated by an intense band at 975 cm(-1)
      assigned to the nu(1) (SO(4))(2-) symmetric stretching mode and Raman bands at
      1077 and 1097 cm(-1) may be attributed to the nu(3) (SO(4))(2-) antisymmetric
      stretching mode. Two Raman bands 1107 and 1126 cm(-1) are assigned to carbonate
      CO(3)(2-) symmetric stretching bands and confirms the presence of carbonate in
      the structure of parnauite. The comparatively sharp band for the Pershing County
      mineral at 976 cm(-1) is assigned to the nu(1) (SO(4))(2-) symmetric stretching
      mode and a broad spectral profile centered upon 1097 cm(-1) is attributed to the
      nu(3) (SO(4))(2-) antisymmetric stretching mode. Two intense bands for the
      Pershing County mineral at 851 and 810 cm(-1) are assigned to the nu(1)
      (AsO(4))(3-) symmetric stretching and nu(3) (AsO(4))(3-) antisymmetric stretching
      modes. Two Raman bands for the French mineral observed at 725 and 777 cm(-1) are
      attributed to the nu(3) (AsO(4))(3-) antisymmetric stretching mode. For the
      French mineral, a low intensity Raman band is observed at 869 cm(-1) and is
      assigned to the nu(1) (AsO(4))(3-) symmetric stretching vibration. Chemical
      composition of parnauite remains open and the question may be raised is parnauite
      a solid solution of two or more minerals such as a copper hydroxy-arsenate and a
      copper hydroxy sulphate.

PMID- 21733747
TI  - Spectroscopic research on ultrahigh pressure (UHP) macrodiamond at Copeton and
      Bingara NSW, Eastern Australia.
AB  - Millions of macrodiamonds were mined from Cenozoic placers across Eastern
      Australia, 98% from within the Copeton and Bingara area (85 km across) in the
      Phanerozoic New England region of New South Wales (NSW). Raman spectroscopy of
      inclusions in uncut diamond, from the Copeton and Bingara parcels, identifies
      them as ultrahigh pressure (UHP) macrodiamond formed during termination of
      subduction by continental collision. Infrared spectral properties of the two
      parcels are critically similar in terms of nitrogen abundance (low in zoned
      diamond, high in unzoned diamond), requiring a pair of different growth
      mechanisms/protoliths. Within each parcel, the degrees of nitrogen aggregation
      are relatively strong and coherent, but they are so different from each other
      (moderate aggregation for Bingara, strong for Copeton) that the two parcels
      require separate primary and local sources. The local sources are post-tectonic
      alkali basaltic intrusions which captured UHP minerals (garnet, pyroxene,
      diamond) from eclogite-dominated UHP terranes (density stranded at depth-mantle,
      lower crust). X-ray diffraction studies on Copeton diamond indicate a normal
      density, despite previous reports of anomalously high density. For non
      fluorescent diamond, a 2nd order Raman peak, which is prominent in theoretical
      perfect diamond and in African cratonic diamond, is suppressed in Copeton and
      Bingara UHP macrodiamond. Pervasive deformation during macrodiamond growth
      probably causes this suppression, the strong nitrogen aggregation, and the
      exceptional durability documented through industrial use.

PMID- 21733748
TI  - Experimental and theoretical study of the exited state of aminostyryl terpyridine
      derivatives: hydrogen-bonding effects.
AB  - The synthesis, structure and photophysical behavior of the aminostyryl
      terpyridine derivatives, named 4'-(4-{2-[4-(N,N-dimethylaniline)]vinyl}phenyl)
      2,2':6',2"-terpyridine (M(1)) and the related model compounds 4'-(4-{2-[4-(N,N
      diphenylammino)phenyl]vinyl}phenyl)-2,2':6',2"-terpyridine (M(2)), respectively,
      are reported. Large solvatochromic shifts of the first excited-state fluorescence
      maximum suggest the intramolecular charge transfer characters for both compounds.
      In addition, with N,N-dimethyl substituents, its fluorescence is quenched a lot
      in protic solvents. This is consisted with the decay of its S(1) state, through
      nonradiative internal conversion, to the ground state, which is facilitated by
      the formation of the hydrogen bond between M(1) and alcohols. Whereas, the
      introduction of N,N-diphenyl substituents has been proved to be a hydrogen-bond
      free case with the unchanged Phi(f). Furthermore, the formation of TICT state via
      diffusive twisting motion of the dimethyl/phenylamino group is the major
      relaxation process, which is proved by the ultrafast relaxation dynamics
      experiment and theoretically conformational optimization of the first excited
      state of both the compounds.

PMID- 21733749
TI  - Study of catalytic reduction and photodegradation of methylene blue by
      heterogeneous catalyst.
AB  - The photocatalytic degradation of methylene blue is investigated in aqueous
      solution containing CoS/nanoAl-MCM-41 photocatalyst under visible light. The
      catalyst is characterized by X-ray diffraction (XRD), UV-vis diffused reflectance
      spectra (UV-vis DRS) and transmission electron microscopy (TEM) techniques. The
      effect of CoS, nanoAl-MCM-41 support and different wt% of CoS over the support on
      the photocatalytic degradation and influence of parameters such as CoS loading,
      catalyst amount, pH and initial concentration of methylene blue on degradation
      are evaluated. Hypsochromic effects (i.e. blue shifts of spectral bands)
      resulting from N-demethylation of the dimethylamino group in methylene blue
      occurs in presence of CoS/nanoAl-MCM-41 under ambient condition. Meanwhile, the
      bleaching of methylene blue MB, by sulfide ion, in an aqueous solution is studied
      in the presence nanoAl-MCM-41 catalyst. In the presence of sulfide ions, MB is
      bleached to its colorless leuco (LMB) and MBH(2)(+) forms. In an acidified
      solution (pH<2) the bleaching process generates LMB and by changing pH between
      2.0 and 7.0 bleaching of MB dye to MBH(2)(+) form is observed. Using nanoAl-MCM
      41 with encapsulated CoS nanoparticles only causes demethylation of MB in aqueous
      solution.

PMID- 21733750
TI  - Synthesis, X-ray crystal structure and fluorescent spectra of novel pyrazolo[1,5
      a]pyrazin-4(5H)-one derivatives.
AB  - A series of fluorescent compounds, containing pyrazolo[1,5-a]pyrazin-4(5H)-one
      moiety, were designed and synthesized from ethyl 1-(2-oxo-2-phenylethyl)-3-phenyl
      1H-pyrazole-5-carboxylates. The structures of the compounds have been confirmed
      by IR, (1)H NMR, HRMS and X-ray crystal diffraction. The optical properties of
      the compounds were investigated by UV-vis absorption and fluorescence
      spectroscopy. The effect of pH on the UV-vis absorption of compound 2a in
      methanol-H(2)O solutions was studied and interpreted by theory calculation. The
      pK(a) value of compound 2a was determined by the absorption spectra.

PMID- 21733751
TI  - High kurtosis of intracranial electroencephalogram as a marker of ictogenicity in
      pediatric epilepsy surgery.
AB  - OBJECTIVE: We determined whether kurtosis analysis of intracranial
      electroencephalogram (EEG) can estimate the localization of the epileptogenic
      zone. METHODS: We analyzed 29 pediatric epilepsy patients who underwent
      intracranial EEG before focal resective surgery. We localized the brain regions
      with high kurtosis, the seizure onset zone (SOZ) and the regions with high-rate,
      high-amplitude and long-duration interictal paroxysms >=20 Hz. We tested
      correlations between the surgical resection of those regions and post-surgical
      seizure outcome, and correlations between kurtosis and the
      rate/amplitude/duration of interictal paroxysms. RESULTS: The resection of the
      regions with high kurtosis correlated with 1-year post-surgical seizure outcome
      (p=0.028) but not with 2-year outcome. Kurtosis showed more significant
      correlation with 1-year seizure outcome than the SOZ and the
      rate/amplitude/duration of interictal paroxysms. Kurtosis showed positive,
      independent correlations with the amplitude and duration of interictal paroxysms
      (p<0.0001) but not with the rate (p=0.4). CONCLUSIONS: The regions with high
      kurtosis provide more reliable information to predict seizure outcome than the
      SOZ and the regions with high-rate/amplitude and long-duration interictal
      paroxysms. Kurtosis reflects combined effects of the amplitude and duration of
      the interictal paroxysms. SIGNIFICANCE: High kurtosis suggests the regions with
      acquired ictogenicity within the irritative zone.

PMID- 21733752
TI  - Development and validation of a subjective post sleep diary (SPSD) to assess
      sleep status in subjects with restless legs syndrome.
AB  - OBJECTIVE: To describe the development and psychometric properties of a daily
      subjective (patient-reported) sleep diary, the Subjective Post Sleep Diary
      (SPSD), that assesses sleep in relation to Restless Legs Syndrome (RLS). METHODS:
      In 2008, the SPSD was developed de novo guided by input from 56 individuals in
      the US with RLS obtained via focus groups and one-on-one cognitive debriefing
      sessions. The psychometric properties of the SPSD were evaluated among an
      additional 470 RLS subjects in the US using three different administration
      routes; the internet only (N=130), an Interactive Voice Response System (IVRS;
      N=146) only and a hybrid version (internet and/or IVRS; N=194). RESULTS: A 12
      item sleep diary assessing the key sleep parameters associated with RLS was
      developed and shown to have face validity following several rounds of focus
      groups and cognitive debriefing sessions. The SPSD items had high correlations
      with other sleep instruments and low correlations with constructs unrelated to
      sleep, and high known-groups predictive ability. CONCLUSIONS: The Subjective Post
      Sleep Diary (SPSD) is a short, valid and responsive instrument for measuring RLS
      related sleep via the internet, IVRS or a combination of the two modes for US
      English speakers.

PMID- 21733753
TI  - NLRP3 inflammasomes link inflammation and metabolic disease.
AB  - A strong link between inflammation and metabolism is becoming increasingly
      evident. A number of recent landmark studies have implicated the activation of
      the NLRP3 inflammasome, an interleukin-1beta family cytokine-activating protein
      complex, in a variety of metabolic diseases including obesity, atherosclerosis
      and type 2 diabetes. Here, we review these new developments and discuss their
      implications for a better understanding of inflammation in metabolic disease, and
      the prospects of targeting the NLRP3 inflammasome for therapeutic intervention.

PMID- 21733754
TI  - PKC-theta function at the immunological synapse: prospects for therapeutic
      targeting.
AB  - Protein kinase C (PKC)-theta regulates conventional effector T (Teff) cell
      function. Since this initial finding, it has become clear that the role of PKC
      theta in T cells is complex. PKC-theta plays a central role in Teff cell
      activation and survival, and negatively regulates stability of the immunological
      synapse (IS). Recent studies demonstrated that PKC-theta is required for the
      development of natural CD4(+)Foxp3(+) regulatory T (Treg) cells, and mediates
      negative regulation of Treg cell function. Here, we examine the role of PKC-theta
      in the IS, evidence for its distinct localization in Treg cells and the
      therapeutic implications of inhibiting PKC-theta in Teff cells, to reduce
      effector function, and in Treg cells, to increase suppressor function, for the
      prevention and treatment of autoimmune and alloimmune disease states.

PMID- 21733755
TI  - Pathology of post primary tuberculosis of the lung: an illustrated critical
      review.
AB  - Post primary tuberculosis occurs in immunocompetent adults, is restricted to the
      lungs and accounts for 80% of all clinical cases and nearly 100% of transmission
      of infection. The supply of human tissues with post primary tuberculosis
      plummeted with the introduction of antibiotics decades before the flowering of
      research using molecular methods in animal models. Unfortunately, the paucity of
      human tissues prevented validation of the models. As a result, it is a paradigm
      of contemporary research that caseating granulomas are the characteristic lesion
      of all tuberculosis and that cavities form when they erode into bronchi. This
      differs from descriptions of the preantibiotic era when many investigators had
      access to thousands of cases. They reported that post primary tuberculosis begins
      as an exudative reaction: a tuberculous lipid pneumonia of foamy alveolar
      macrophages that undergoes caseation necrosis and fragmentation to produce
      cavities. Granulomas in post primary disease arise only in response to old
      caseous pneumonia and produce fibrosis, not cavities. We confirmed and extended
      these observations with study of 104 cases of untreated tuberculosis. In
      addition, studies of the lungs of infants and immunosuppressed adults revealed a
      second type of tuberculous pneumonia that seldom produces cavities. Since the
      concept that cavities arise from caseating granulomas was supported by studies of
      animals infected with Mycobacterium bovis, we investigated its pathology. We
      found that M. bovis does not produce post primary tuberculosis in any species. It
      only produces an aggressive primary tuberculosis that can develop small cavities
      by erosion of caseating granulomas. Consequently, a key unresolved question in
      the pathogenesis of tuberculosis is identification of the mechanisms by which
      Mycobacterium tuberculosis establish a localized safe haven in alveolar
      macrophages in an otherwise solidly immune host where it can develop conditions
      for formation of cavities and transmission to new hosts.

PMID- 21733756
TI  - The increasing importance of Intellectual Property in Transfusion Medicine.
AB  - The Scottish National Blood Transfusion Service (SNBTS) originated in Edinburgh
      in the 1920's by dentist Jack Copland. Since that time the scope of Transfusion
      Medicine has broadened significantly to accommodate advances in technologies such
      as cell isolation, culture and manipulation. Many transfusion services, including
      SNBTS, now provide expertise both in the traditional field of blood transfusion
      and the newer, wider field of human cell (including 'adult' and embryonic stem
      cells) and tissue procurement and culture - in all the new science of
      "regenerative medicine". This paper describes the importance of Intellectual
      Property in the provision of Transfusion Medicine today and provides guidance on
      the management of Intellectual Property so that advances in the field have the
      best chance of successful translation into clinical practice.

PMID- 21733757
TI  - Cladribine as a therapeutic option in multiple sclerosis.
AB  - There is an unmet need for more potent and convenient drugs in the treatment of
      patients diagnosed with multiple sclerosis (MS). Among five currently
      investigated oral drugs with an ongoing or completed phase III program, promising
      efficacy data for oral cladribine have recently been published. However, benefits
      need to be weighed against potential risks to define the role of this compound
      within current treatment regimens. Here we review present data on efficacy of
      oral cladribine and discuss known and anticipated risks of this drug.

PMID- 21733758
TI  - Randomized comparison of the Personality Assessment Inventory and the Minnesota
      Multiphasic Personality Inventory-2 in the epilepsy monitoring unit.
AB  - The two most common personality measures used in evaluation of patients on
      epilepsy monitoring units (EMUs) are the Personality Assessment Inventory (PAI)
      and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Both have been
      evaluated separately for their ability to distinguish patients with epilepsy from
      patients with psychogenic events, but they have never been compared directly. The
      primary aim of this study was to provide comparison data in an EMU population
      between the PAI, MMPI-2, and the MMPI-2-RF (MMPI-2 Restructured Form). Results
      show that the PAI Somatic Complaints (SOM) scale and the Conversion subscale (SOM
      C), with classification rates of 79%, outperform other indicators from the PAI
      and indicators from the MMPI-2 and the MMPI-2-RF. Given its other strengths
      combined with better diagnostic validity performance, the PAI may be the better
      personality assessment measure for use in distinguishing patients with epilepsy
      from those with psychogenic seizures in the EMU.

PMID- 21733759
TI  - No response to acoustic stimuli: absence or akinetic seizure?
AB  - Absence seizures are defined by a loss of consciousness during generalized spike
      wave discharges (SWCs). We describe a patient who did not respond to acoustic
      stimuli during generalized SWCs, but who had full recall of any test word given
      during the SWCs. Our patient's inability to move illustrates that the clinical
      features during generalized SWCs need to be tested differentially. This pertains
      especially to studies that evaluate the pathophysiological correlates during
      SWCs.

PMID- 21733760
TI  - Use of rosiglitazone and pioglitazone immediately after the cardiovascular risk
      warnings.
AB  - BACKGROUND: Meta-analyses of oral hypoglycemic agents (OHAs) revealed that
      rosiglitazone increased the risk of myocardial infarction (MI) and heart failure
      (HF) and that pioglitazone increased the risk of HF and decreased the risk of MI.
      OBJECTIVE: To characterize the change in the pattern of use of OHAs immediately
      after the publication of these meta-analyses on May 21, 2007. METHODS: Pharmacy
      and medical claims data for a managed care organization were analyzed for
      patients continuously enrolled from January 1, 2005, to November 30, 2007, with
      at least 1 pharmacy claim for OHA in the 13-month period between November 1,
      2006, and November 30, 2007. A 5-month pre-publication period (November 1, 2006,
      through March 31, 2007) was compared with a 5-month post-publication period (July
      1, 2007, through November 30, 2007) using a differences-in-differences
      multinomial logistic regression. This regression explored discontinuation;
      continuation with monotherapy or adding another drug; and switching to a drug
      different from the index monotherapy drug after adjusting for gender, age, type
      of insurance, past 1-year history of MI or HF, and risk factors for MI and HF in
      the past 1 year. RESULTS: The relative rate of switching to nonindex drug in the
      postpublication relative to prepublication was 2.64 (P=.046) for monotherapy
      rosiglitazone users and 0.72 (P=.583) for monotherapy pioglitazone users. The
      differences-in-differences estimate of the rate of switching to nonindex drugs
      for monotherapy rosiglitazone users was 3.64 (P=.090) times higher relative to
      the estimate for monotherapy pioglitazone users. CONCLUSION: The pattern of use
      differed fundamentally between monotherapy rosiglitazone users and users of all
      other monotherapy OHAs in the postperiod. Not only were monotherapy rosiglitazone
      patients switching to non-rosiglitazone drugs at a higher rate, but the rate also
      was more than 3 times higher than similar switches among monotherapy pioglitazone
      users in the postperiod relative to the preperiod. This shows that the market
      response as observed by patient/prescriber decisions to the adverse news was
      interpreted narrowly to monotherapy rosiglitazone, and there is little or no
      spillover to the other drugs. Therefore, this study found that there was a
      differential effect of meta-analyses on the use of the 2 drugs.

PMID- 21733761
TI  - Increased difficulties and complications encountered during hysteroscopy in women
      with genital tuberculosis.
AB  - BACKGROUND: Genital tuberculosis (TB) in women is a common disease in developing
      countries, and hysteroscopy and laparoscopy are vital tools in diagnosis. STUDY
      OBJECTIVE: To retrospectively compare the difficulties encountered and
      complications of hysteroscopy in women with and without genital TB. DESIGN: Case
      control clinical audit (Canadian Task Force classification II-1). SETTING:
      Medical college and hospital. PATIENTS: Ninety-nine women who underwent
      hysteroscopy, with or without other procedures, who were found to have genital TB
      at various investigations (group 1) and 289 women who underwent hysteroscopy
      during the same period with similar characteristics but without evidence of
      genital TB (group 2, controls). INTERVENTION: Hysteroscopy. MEASUREMENTS AND MAIN
      RESULTS: Difficulties encountered and complications observed were recorded,
      compared, and analyzed using the chi(2) and Fisher exact tests. Indications for
      hysteroscopy in the study vs the control group were infertility in 92 patients
      (92.92%) vs 124 (42.90 %), amenorrhea in 6 (6.66%) vs 12 (4.15%), and
      postmenopausal bleeding in 1 (1.11%) vs 29 (10.03%). Difficulties and
      complications were significantly higher in group 1. Inability to distend the
      cavity was observed in 8 women in group 1 (8.08%) vs 2 in group 2 (0.69%).
      Excessive bleeding was observed in 5 women in group 1 (5.05%) vs 1 in group 2
      (0.35 %). Uterine perforation was observed in 8 women in group 1 (8.08%) vs 5 in
      group 2 (1.73%), and flare-up of genital TB was observed in 1 woman in group 1.
      CONCLUSION: Hysteroscopy in women with genital TB is associated with difficulty
      in performing the procedure and with higher rates of complications.

PMID- 21733762
TI  - Glucose sensing by electrogenerated chemiluminescence of glucose-dehydrogenase
      produced NADH on electrodeposited redox hydrogel.
AB  - In this work, we report a new sensing approach based on electrogenerated
      chemiluminescence (ECL) in an electrodeposited redox hydrogel using glucose
      dehydrogenase as a model system. The ECL-hydrogel films were electrodeposited by
      potential cycling of a PBS solution containing [poly(4-vinylpyridine)Ru(2,2'
      bipyridine)(2)Cl(-)](+/2+). The film was easily prepared in a rapid, reproducible
      and well-controlled one-step procedure. The deposited hydrogel film is permeable
      to water-soluble chemicals and biochemicals, like enzyme substrates and
      coenzymes. Electrochemistry and ECL of NADH were studied at the level of the
      hydrogel film. Results indicate that ECL emission occurs at a relatively low
      anodic potential compared to the classical Ru(bipy)(3)(2+) complex. This is an
      important advantage since the measurements performed with the ECL hydrogel are
      thus less sensitive to interfering species. An ECL oxidative-reductive mechanism
      is presented for the ECL-hydrogel. Then we showed that the intensity of the ECL
      of NADH produced by the enzymatic activity varies with the enzyme substrate
      concentration. Such sensing approach combines enzymatic selectivity with the ECL
      advantages at low oxidation potential.

PMID- 21733763
TI  - Quantification of acetaminophen (paracetamol) in human plasma and urine by stable
      isotope-dilution GC-MS and GC-MS/MS as pentafluorobenzyl ether derivative.
AB  - We report on the quantitative determination of acetaminophen (paracetamol; NAPAP
      d(0)) in human plasma and urine by GC-MS and GC-MS/MS in the electron-capture
      negative-ion chemical ionization (ECNICI) mode after derivatization with
      pentafluorobenzyl (PFB) bromide (PFB-Br). Commercially available tetradeuterated
      acetaminophen (NAPAP-d(4)) was used as the internal standard. NAPAP-d(0) and
      NAPAP-d(4) were extracted from 100-MUL aliquots of plasma and urine with 300 MUL
      ethyl acetate (EA) by vortexing (60s). After centrifugation the EA phase was
      collected, the solvent was removed under a stream of nitrogen gas, and the
      residue was reconstituted in acetonitrile (MeCN, 100 MUL). PFB-Br (10 MUL, 30
      vol% in MeCN) and N,N-diisopropylethylamine (10 MUL) were added and the mixture
      was incubated for 60 min at 30  degrees C. Then, solvents and reagents were
      removed under nitrogen and the residue was taken up with 1000 MUL of toluene,
      from which 1-MUL aliquots were injected in the splitless mode. GC-MS
      quantification was performed by selected-ion monitoring ions due to [M-PFB](-)
      and [M-PFB-H](-), m/z 150 and m/z 149 for NAPAP-d(0) and m/z 154 and m/z 153 for
      NAPAP-d(4), respectively. GC-MS/MS quantification was performed by selected
      reaction monitoring the transition m/z 150 -> m/z 107 and m/z 149 -> m/z 134 for
      NAPAP-d(0) and m/z 154 -> m/z 111 and m/z 153 -> m/z 138 for NAPAP-d(4). The
      method was validated for human plasma (range, 0-130 MUM NAPAP-d(0)) and urine
      (range, 0-1300 MUM NAPAP-d(0)). Accuracy (recovery, %) ranged between 89 and
      119%, and imprecision (RSD, %) was below 19% in these matrices and ranges. A
      close correlation (r>0.999) was found between the concentrations measured by GC
      MS and GC-MS/MS. By this method, acetaminophen can be reliably quantified in
      small plasma and urine sample volumes (e.g., 10 MUL). The analytical performance
      of the method makes it especially useful in pediatrics.

PMID- 21733764
TI  - [Chronic autoimmune urticaria as a possible non endocrine manifestation of
      autoimmune polyglandular syndrome type II].

PMID- 21733765
TI  - Successful endoscopic removal of metal vascular coils from the biliary tree.

PMID- 21733766
TI  - Endoscopic ultrasonography-guided fine needle aspiration biopsy using 22-gauge
      needle in diagnosis of autoimmune pancreatitis.
AB  - BACKGROUNDS: The effectiveness of endoscopic ultrasonography-guided fine-needle
      aspiration (EUS-FNA) has not been fully evaluated in the diagnosis of autoimmune
      pancreatitis (AIP). AIM: To evaluate the effectiveness of EUS-FNA using 22-gauge
      needles in the diagnosis of AIP. METHODS: EUS-FNA was examined in 85 patients
      with pancreatic mass, including 64 patients with pancreatic cancer and 21
      patients with AIP. We investigated ability of EUS-FNA using 22-gauge needle for
      the differential diagnosis between AIP and pancreatic cancer. We also compared
      the factors concerning FNA procedures (number of needle passes, size of lesion,
      device, and amount of obtained pancreatic tissue) between two diseases. RESULTS:
      Tissues obtained from 21 patients with AIP, although none of them demonstrated
      histology suspicious for malignancy, did not show histological evidence
      definitive for AIP. The amount of obtained pancreatic tissue was almost equal
      between two diseases in each pancreatic location. Sensitivity, specificity,
      overall accuracy, and negative predictive value of histological diagnosis of
      pancreatic cancer were 92.2%, 100%, 94.1%, and 80.8%, respectively. CONCLUSION:
      EUS-FNA using 22-gauge needle distinguished benign from malignant pancreatic mass
      with >90% of accuracy, regardless of the location. Hence, it was helpful for the
      clinical diagnosis of AIP, however not providing satisfactory samples for the
      histological diagnosis of AIP.

PMID- 21733767
TI  - A man with hepatocellular carcinoma presenting as erythroderma.

PMID- 21733768
TI  - Precut sphincterotomy, repeated cannulation and post-ERCP pancreatitis in
      patients with bile duct stone disease.
AB  - BACKGROUND: Repeated attempts at cannulating the papilla of Vater and "needle
      knife" precut sphincterotomy are independent risk factors for post-ERCP
      pancreatitis. Whether precut alone or repeated attempts at cannulation is the
      culprit factor in the development of post-ERCP pancreatitis remains
      controversial. AIM: To retrospectively assess the role of precutting and multiple
      cannulation in the occurrence of post-ERCP pancreatitis in a consecutive series
      of patients with bile stone disease. METHODS: 2004 patients who had undergone
      endoscopic retrograde cholangio-pancreatography over a 9-year period for bile
      stones were evaluated. Pancreatitis rate was assessed in relation to the number
      of cannulation attempts (<10 and >=10) and precutting. RESULTS: Procedures were
      successful in 1878 patients (93.7%). Cannulation was done without precutting in
      1717 cases and with in 161. Pancreatitis occurred in 2.7% of patients who had
      undergone biliary cannulation without precutting and in 6.5% with (p=0.006). It
      was lower with <10 attempts than with >=10 (p<0.0001), either without (p<0.0001)
      or with precutting (p<0.01). Pancreatitis rate did not differ without and with
      precutting when <10 attempts at cannulation were done, whilst it was lower when
      precut was done before 10 attempts than when 10 or more attempts were made
      without precutting (p=0.02). CONCLUSIONS: Pancreatitis rate was lower when precut
      was done with <10 attempts than when >=10 attempts were made without precutting.
      In experienced hands precut biliary sphincterotomy does not seem to be an
      independent risk factor for post-ERCP pancreatitis in patients undergoing
      endoscopic retrograde cholangio-pancreatography for bile duct stones.

PMID- 21733769
TI  - Spontaneous portal vein arterialization in hepatic artery thrombosis.

PMID- 21733770
TI  - [Peliosis hepatitis secondary to hormone treatment].

PMID- 21733771
TI  - Allelic drop-out probabilities estimated by logistic regression--further
      considerations and practical implementation.
AB  - We discuss the model for estimating drop-out probabilities presented by
      Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of
      the model has demonstrated that the model is not perfect. However, the model is
      very useful for advanced forensic genetic work, where allelic drop-out is
      occurring. With this discussion, we hope to improve the drop-out model, so that
      it can be used for practical forensic genetics and stimulate further discussions.
      We discuss how to estimate drop-out probabilities when using a varying number of
      PCR cycles and other experimental conditions.

PMID- 21733772
TI  - Comments on: "Is alumina-on-alumina ceramic bearings total hip replacement the
      right choice in patients younger than 50 years of age? A 7- to 15-year follow-up
      study" by P. Boyer, D. Huten, P. Loriaut, V. Lestrat, C. Jeanrot, P. Massin,
      published in Orthop Traumatol Surg Res 2010;96:616-22.

PMID- 21733773
TI  - ERAS - enhanced recovery after surgery.

PMID- 21733774
TI  - Support vector machines with constraints for sparsity in the primal parameters.
AB  - This paper introduces a new support vector machine (SVM) formulation to obtain
      sparse solutions in the primal SVM parameters, providing a new method for feature
      selection based on SVMs. This new approach includes additional constraints to the
      classical ones that drop the weights associated to those features that are likely
      to be irrelevant. A nu-SVM formulation has been used, where nu indicates the
      fraction of features to be considered. This paper presents two versions of the
      proposed sparse classifier, a 2-norm SVM and a 1-norm SVM, the latter having a
      reduced computational burden with respect to the first one. Additionally, an
      explanation is provided about how the presented approach can be readily extended
      to multiclass classification or to problems where groups of features, rather than
      isolated features, need to be selected. The algorithms have been tested in a
      variety of synthetic and real data sets and they have been compared against other
      state of the art SVM-based linear feature selection methods, such as 1-norm SVM
      and doubly regularized SVM. The results show the good feature selection ability
      of the approaches.

PMID- 21733775
TI  - [What is the place of the Anatolian Journal of Cardiology in the World?].

PMID- 21733776
TI  - [Interview with Prof. Dr. Ali Ekmekci by Prof. Dr. Yilmaz Nisanci].

PMID- 21733777
TI  - Witnessing a rare event: thrombus in transit after coronary angiography.

PMID- 21733778
TI  - Supravalvular pulmonary stenosis due to hydatid cyst.

PMID- 21733779
TI  - Diagnosis of a caseous mitral annular calcification.

PMID- 21733780
TI  - A ring in the heart: an atrial septal aneurysm.

PMID- 21733781
TI  - Slowly progressive conduction system disturbance in a patient with polymyositis.

PMID- 21733782
TI  - Thirty-six years with the same prosthetic mitral valve.

PMID- 21733783
TI  - QT interval prolongation due to metronidazole administration.

PMID- 21733784
TI  - [Effects of patient education and counseling about life style on quality of life
      in patients with coronary artery disease].

PMID- 21733785
TI  - [Augmentation of vessel narrowing by nitroglycerine in a case with myocardial
      bridge].

PMID- 21733786
TI  - Late bare-metal stent thrombosis in a patient with Crohn's disease.

PMID- 21733787
TI  - Embolic acute myocardial infarction treated by intracoronary catheter aspiration
      embolectomy in a patient with mechanical aortic valve prosthesis.

PMID- 21733788
TI  - [Two situations, which are difficult to differentiate from each other: plagiarism
      and duplication].

PMID- 21733789
TI  - [Valve-sparing operation for ascending aorta aneurysm].

PMID- 21733790
TI  - Functional mitral regurgitation and papillary muscle dyssynchrony in patients
      with left ventricular systolic dysfunction.
AB  - In a dilated heart with impaired systolic functions, functional mitral
      regurgitation could be seen even in the presence of structurally normal mitral
      apparatus. A number of mechanisms play role in the development of functional
      mitral regurgitation. These are increased mitral tethering forces, reduction in
      closing forces and mechanical and electrical dyssynchrony. Papillary muscle
      dyssynchrony has also been shown to be related with functional mitral
      regurgitation. Cardiac resynchronization therapy is known to reduce the amount of
      functional mitral regurgitation in patients with left ventricular systolic
      failure although some may not respond to treatment with cardiac resynchronization
      therapy. Papillary muscle dyssynchrony may predict the response of cardiac
      resynchronization therapy on the regression of functional mitral regurgitation
      and may suggest the suitable therapeutic options, such as cardiac
      resynchronization therapy, mitral valve repair, coronary revascularization
      separately or in combination. In this review, the mechanisms of functional mitral
      regurgitation, papillary muscle dyssynchrony and its relationship with functional
      mitral regurgitation and the relationship of papillary muscle dyssynchrony with
      the improvement of functional mitral regurgitation after cardiac
      resynchronization therapy are focused.

PMID- 21733791
TI  - [Management of lung cancer-related pain].
AB  - Pain occurs in seventy-four percent of patients suffering from advanced lung
      cancer, and eighty-two percent of patients feels that the applied treatment of
      pain was inefficient. The management of cancer-related pain is based on the WHO
      analgesic ladder. The ladder has three steps. Step one involves the use of
      nonsteroidal anti-inflammatory drugs for mild pain, step two mild opioids for
      moderate pain and step three strong opioids for the treatment of heavy pain. This
      management - in case of emergency - is supplemented by interventional procedures
      (nerve blockades, surgery). The most effective pain-killing intervention is the
      all-round oncological and surgical therapy. The different treatments
      (oncological, radiological, surgical, drug and interventional) are applied in
      combination with each other. The paper is dealt with the possibility offered by
      the drug and interventional treatments.

PMID- 21733792
TI  - [Mephedrone -- an old-new drug of abuse].
AB  - New natural and synthetic compounds are continuously introduced into the illicit
      drug market. Their origin, composition, main and side-effects are often not
      exactly known by the users themselves. Thus, the control of these substances is
      extremely difficult. AIMS: In year 2008, a new synthetic drug called mephedrone
      (2-metilamino-1-(4-metilfenil) propan-1-on) appeared in Hungary. This work
      summarizes its frequency in biological samples investigated for illicit drugs,
      and experiences of the medical examination of mephedrone-users. METHODS:
      Toxicological analyses of biological samples (urine and/or blood) were carried by
      GC-MS at the Institute of National Toxicology and at Department of Forensic
      Medicine, University Szeged. RESULTS: Altogether 5386 samples were analyzed in
      2010 (4922 in Budapest and 464 in Szeged), and mephedrone was identified in 363
      cases (7%). CONCLUSIONS: Mephedrone is banned in Hungary since January 1st, 2011,
      but it still available in the illegal drug market. At present we do not have
      sufficient experience with its long-term effects, tolerance, addiction,
      withdrawal symptoms or toxic dose. Thus, it is difficult to establish whether
      addiction and/or mental disorder occurred.

PMID- 21733793
TI  - [Complementary therapies--based on the principles of evidence-based medicine.
      Position statement of the Medical Sciences Section of the Hungarian Academy of
      Sciences].

PMID- 21733794
TI  - [Uterine papillary serous carcinoma].

PMID- 21733795
TI  - [History of arteficial deformation of the human body. I. Artificial cranial
      deformation].

PMID- 21733796
TI  - [Role of oncogenetics in the treatment of breast and ovarian cancer].

PMID- 21733797
TI  - Judy Bonds: Environmental leader and organizer 1952-2011.

PMID- 21733798
TI  - From (before) Bhopal to (after) BP: trade secrets and the right to know.
AB  - This paper discuses the tensions between, on the one hand, workers' and
      communities' right to know about occupational and environmental hazards, and on
      the other hand, trade secrets and the rights of their corporate owners. We first
      discuss the role of trade secrets in economic development in the context of the
      benefits claimed for free markets. We then describe the ongoing struggles of
      workers and communities in the United States for access to information about
      hazards. The third section of the paper is a discussion of the reformulation of
      labor and occupational health and safety regulation as matters of human rights,
      again focusing on the situation in the United States. The final section is a
      discussion of the implications of the human rights approach for the occupational
      and environmental health practitioner. Although the paper focuses primarily on
      the U.S. experience, we believe that the lessons learned may be broadly
      applicable.

PMID- 21733799
TI  - Environmental and occupational health and human rights.
AB  - Modern environmental- and occupational-related morbidities and mortality are
      determined by the power relations inherent in our existing capitalist systems of
      production and consumption. These systems thwart human public health rights
      because of the priority to maximize profit for the systems' owners rather than to
      establish ecologically sound and socially just development for all. The
      international public health community must return to its primary prevention roots
      and take action to eliminate the potential for population morbidities that result
      from hazardous substance exposures in work and community environments. The 1988
      Adelaide Recommendations on Healthy Public Policy provide us with guidelines that
      incorporate a human rights approach and build on several decades of international
      public health declarations and charters. To succeed, public health must work with
      the labor movement. A human rights approach to environmental public health can
      help us make a transition to sustainable modes of production and consumption. The
      environmental justice movement's strategy for an economic greening that sets as a
      priority "pathways out of poverty" can help to advance environmental public
      health rights.

PMID- 21733800
TI  - Lessons on corporate "sustainability" disclosure from Deepwater Horizon.
AB  - The BP oil spill highlighted shortcomings of current financial and sustainability
      reporting standards and practice. "Integrated reporting" aims to combine
      financial and social/environmental information into a single annual corporate
      report. But without more stringent standards, integrated reports would neglect
      substantial risks and, as BP's sustainability reports demonstrate, create false
      impressions of good practice.To be of value, integration must: 1. Require timely
      disclosure of enforcement notices, orders and allegations issued by regulators.
      2. Require disclosure of credible scientific reports and concerns indicative of
      potentially catastrophic risks of a company's products and activities, regardless
      of scientific uncertainty. 3. Require review and disclosures of a firm's safety
      culture. 4. Require disclosure of any facts or circumstances needed to ensure
      that the management's self-portrait of its sustainability strategies, goals and
      progress is not materially misleading.In conducting its misleading reporting, BP
      largely followed Global Reporting Initiative (GRI) guidelines. GRI is soliciting
      input, beginning in summer 2011, on how to revise those guidelines. Since GRI may
      prove a leading source for sustainability disclosure rules in integrating
      reporting, lessons learned from the BP experience must be applied to the next GRI
      revisions.

PMID- 21733801
TI  - Response to Lewis's lessons on corporate "sustainability" disclosure from
      Deepwater Horizon.

PMID- 21733802
TI  - Ten years after: is it time to revisit the 1994 OSHA indoor air quality rule?
AB  - Approximately 20 million nonsmoking workers are employed in workplaces without
      restrictions on smoking and are potentially exposed to secondhand smoke--a Class
      A carcinogen. These workers are largely in the service industry, in southern and
      western states and in non-urban areas. The Occupational Safety and Health
      Administration's (OSHA's) 1994 proposal for smoke-free workplaces (withdrawn in
      2001) was attacked by many interest groups that may no longer oppose this
      protection. Federal regulation for smoke-free workplaces is needed for workers,
      who are not protected by state and local smoke-free laws. This policy could save
      thousands of lives each year, and prevent significant illness. Twenty-one states
      have "state plans" that would allow more protective laws. Of the 29 states under
      OSHA, 11 have comprehensive smoke-free statutes. Changes in the policy
      environment and in institutions such as unions, restaurant associations, and the
      tobacco industry since 2001 may improve the prospects for federal action and
      reduce disparities that currently characterize exposure to secondhand smoke.

PMID- 21733803
TI  - Implementation and evaluation of interventions for home care aides on blood and
      body fluid exposure in large-group settings.
AB  - Participatory research conducted with academic, union and management cooperation
      resulted in the development, implementation, and process evaluation of
      interventions designed to reduce occupational blood and body fluid exposure among
      home care aides. Home care aides working for a large urban home care agency took
      part in the design and implementation of an interactive participatory training
      program conducted in large-group settings, and the development and evaluation of
      two training tools: an information card for home care aides and a sharps safety
      magnet for their clients. A process evaluation conducted immediately following
      the interactive training program found that 72 percent of the home care aides
      preferred it to lecture-style trainings typically offered, while only 9 percent
      preferred typical trainings. Home care aides were able to effectively articulate
      information learned during the interactive training program, with less than 2
      percent providing inaccurate information about what was taught during the
      training. Home care aides overall responded positively to the information card
      and the magnet, with aides caring for clients who used sharps rating the tools as
      more useful. Participatory training programs can be effectively implemented in a
      large-group setting.

PMID- 21733804
TI  - Wages, wage violations, and pesticide safety experienced by migrant farmworkers
      in North Carolina.
AB  - Farmworkers have the potential to receive wages that fail to meet minimum wage
      standards. This analysis describes wages and minimum wage violations among
      farmworkers, and it determines associations of wage violations with personal
      characteristics and pesticide safety regulation violations. Data are from a cross
      sectional survey of 300 eastern North Carolina farmworkers conducted in June
      through August, 2009. Most farmworkers (90.0%) were paid by the hour, but 11.7
      percent received piece-rate pay. Wage violations were prevalent among
      farmworkers: 18.3 percent of all farmworkers, 45.3 percent of farmworkers without
      H-2A visas, and 3.6 percent of farmworkers with H-2A visas experienced wage
      violations. Most farmworkers experienced numerous pesticide safety violations.
      Personal characteristics were not associated with wage violations among
      farmworkers without H-2A visas, but some pesticide safety violations were
      associated with wage violations. The association of violations indicates that
      some growers generally violate regulations. Greater enforcement of all
      regulations is needed.

PMID- 21733805
TI  - The "Chair Campaign" in Korea: an alternative approach in occupational health and
      safety for service workers.
AB  - In spite of the increasing number of service workers in Korea, their occupational
      health and safety concerns have largely been neglected. It is in this context
      that the Chair Campaign, which lasted four months, was launched as an alternative
      occupational health approach for service workers. The campaign succeeded in
      getting wide public support, bringing about a special inspection by the Ministry
      of Labor. Finally, chairs were provided for workers at checkout counters in 71
      department stores and 449 large discount stores. However, there are still many
      workplaces where workers cannot sit, whether chairs are provided or not. Although
      there is still much to be done, this campaign raised social awareness that
      service workers, mainly women, have the right to work in healthy and safe
      conditions. This paper will review the campaign and evaluate its achievements and
      limitations.

PMID- 21733806
TI  - Health, safety and environmental education at the Canadian Labour Congress.
AB  - This piece describes involvement and reflections by Dave Bennett in three areas:
      1) union education at the Canadian Labour Congress (CLC) from the late 1970s
      onwards; 2) insights regarding how the CLC moved into health and safety education
      in the early 1980s; and 3) further thoughts on how the CLC moved from health and
      safety into environmental protection education in the early 1990s, and consequent
      changes in the perspective adopted by health and safety courses. There are two
      types of critical comment on these educational processes, one which examines the
      educational dilemmas at the time, with an evaluation of the decisions reached,
      and the other a retrospective view of the educational process as a result of
      reflective hindsight.

PMID- 21733807
TI  - Public health keys for the future.

PMID- 21733808
TI  - Amanda Hawes: a formidable force for chemical companies to contend with in worker
      health and safety cases.

PMID- 21733811
TI  - Put your right hip in, put your right hip out.
AB  - Hip replacement is one of the most common surgical procedures in the United
      States. Among the multiple reasons that joints degenerate, arthritis leads as a
      cause of hip pain and failure. Currently, most artificial joints wear out after
      10 to 20 years, potentially necessitating another surgery. Total hip arthroplasty
      (or total hip replacement) involves replacing the femoral neck and femoral head.
      Devices are held in place using either cement, cementless, or hybrid procedures.
      Although it occurs in fewer than 1% of procedures, infection can be devastating
      and lead to the need for multiple surgeries. Today, several options are available
      when hip replacement is needed. Minimally invasive surgery (MIS) employs the same
      procedures and materials used in conventional hip surgery but results in less
      soft-tissue dissection. MIS anterior-hip arthroplasty is a variant of MIS that
      shortens recovery time. Hip resurfacing spares the femoral head and is generally
      viewed as a more complicated procedure that may be more appropriate for younger,
      more active patients. Computed-assisted surgery may allow better positioning of
      the acetabular component of the prosthesis. Two developing issues related to
      devices used for hip replacement are device recall and device registries.

PMID- 21733812
TI  - Medication administration: are you up to date?
AB  - Pharmacists working in long-term care facilities are often called upon to educate
      nurses and other care staff on proper medication-administration technique. New
      medications, as well as new drug-delivery methods for older medications, require
      all health care practitioners to learn about the specific manufacturers'
      recommendations for each product. In addition, keeping abreast of current
      infection-control standards is imperative for all staff administering
      medications.

PMID- 21733813
TI  - Reasons for bisphosphonate exclusion in patients treated for osteoporosis.
AB  - OBJECTIVE: Inadequate treatment is a concern in management of osteoporosis
      because of its negative impact on fracture risk, health care costs, and quality
      of life. Bisphosphonates are the most effective drug class at decreasing hip and
      spine fractures. The purpose of the study was to discover reasons for exclusion
      of bisphosphonates in the treatment of patients with osteoporosis. DESIGN: A
      cross-sectional study of electronic medical records. SETTING: Academic family
      medicine outpatient clinics. PATIENTS: Subset of patients older than 25 years of
      age who had a diagnosis of osteoporosis and were not on bisphosphonate treatment
      on December 31, 2007. OUTCOMES: The primary endpoint was the reason patients were
      not on bisphosphonate therapy. Secondary endpoints included the length of
      previous bisphosphonate therapy and the number of patients receiving other
      prescription treatments for osteoporosis. RESULTS: Of 698 patients with
      osteoporosis, 418 (60%) were not treated with a bisphosphonate. Patients were
      91.6% female and 76.4% white, with a mean age of 77.5 +/- 13.5 years. Of the
      random sample of 191 patients, 17 (8.9%) patients did not have an identifiable
      reason for bisphosphonate exclusion. The most common reasons were
      gastrointestinal (GI) diagnosis (28%), low functional status (24%), and poor
      renal function (12%). Almost half (44.5%) of patients were previously on a
      bisphosphonate, with an average use of 20.7 +/- 17.7 months. Only 2.6% of
      patients received osteoporosis treatment other than a bisphosphonate. CONCLUSION:
      Even though 60% of patients were not prescribed a bisphosphonate, 91.1% had a
      reason for exclusion. With GI reasons most common, parenteral forms of
      bisphosphonates recently approved for osteoporosis may increase use.

PMID- 21733814
TI  - Insomnia: a therapeutic review for pharmacists.
AB  - OBJECTIVE: To review the literature for the management of insomnia. DATA SOURCE:
      MEDLINE/PUBMED searches (January 1950-June 2010) were conducted to identify
      pertinent English-language studies. STUDY SELECTION AND DATA EXTRACTION: All
      studies evaluating aspects of the treatment of insomnia. DATA SYNTHESIS: Insomnia
      is a major public health problem requiring effective diagnosis and treatment.
      Treatment options include cognitive behavioral therapy as well as pharmacologic
      therapy. Benzodiazepine receptor-agonist modulators are considered first-line
      therapy in the treatment of chronic insomnia. A nonbenzodiazepine receptor
      modulator option to improve sleep latency is ramelteon. Low-dose sedative
      antidepressants, such as quetiapine or olanzapine, may be used in the treatment
      of comorbid insomnia. Over-the-counter and herbal agents are not recommended.
      CONCLUSION: Numerous medications being used in the management of insomnia have
      side effects that can limit their use and have a potential for drug interactions.
      Furthermore, some medications used in the treatment of insomnia do not have
      clinical trial data to support their use. Future studies are warranted to define
      second- and third-line agents in the management of insomnia.

PMID- 21733815
TI  - Trimethoprim-sulfamethoxazole-induced hyponatremia.
AB  - An 86-year-old Caucasian male developed hyponatremia while on trimethoprim
      sulfamethoxazole (TMP-SMX) 80/400 mg, one tablet by mouth twice daily. Upon
      discontinuation of therapy, his serum sodium and symptoms improved. He was
      inadvertently rechallenged several months later with TMP-SMX and had similar
      symptoms and laboratory abnormalities. TMP-SMX-induced hyponatremia is a rare
      occurrence. Previous publications have most often reported this phenomenon in
      combination with hyperkalemia. However, this patient represents a case of TMP-SMX
      induced hyponatremia independent of hyperkalemia and provides a rare opportunity
      to observe a challenge and rechallenge with the offending medication. Although
      the mechanism behind this adverse drug reaction remains unclear, a score of 7 on
      the Naranjo probability scale indicates a probable likelihood that TMP-SMX was
      the cause of the hyponatremia in this patient. This case demonstrates that TMP
      SMX can result in the development of hyponatremia independent of hyperkalemia.
      Health care providers should be aware of the potential for hyponatremia
      associated with TMP-SMX and consider monitoring electrolytes and renal function
      during therapy.

PMID- 21733816
TI  - Immigrants: distinct differences, increasing insight.

PMID- 21733817
TI  - The dawn of a revolution in personalized lung cancer prevention.
AB  - Lung cancer prevention and early detection, which have fallen on hard times for
      more than the past 20 years, seem to have turned a corner toward better times
      ahead. Exciting new results of randomized controlled trials that targeted the
      arachidonic acid pathway, including a celecoxib trial reported by Mao and
      colleagues in this issue of the journal (beginning on page 984) and a trial of
      the prostacyclin analog iloprost, complement recently reported 20%-30% lung
      cancer mortality reductions, either with aspirin in targeting the arachidonic
      acid pathway or with computed tomography screening. The new results show
      encouraging activity personalized to former smokers and/or people expressing
      predictive biomarkers. These trials and technological advances in molecular
      profiling and imaging herald substantial clinical advances on the horizon of this
      field.

PMID- 21733818
TI  - Cancer vaccines: moving toward prevention?
AB  - After several decades of research, recent successful phase III controlled
      clinical trials have renewed enthusiasm for vaccine treatment of cancer. This
      perspective on the report by Berta and colleagues in this issue of the journal
      (beginning on page 994) discusses the potential prevention of oral cancer through
      vaccine strategies and, in the broader context, ideal characteristics of tumor
      antigens as candidates for vaccines for both treating and preventing cancer,
      potential primary and secondary prevention settings for vaccines, desirable types
      of immune effectors induced by vaccines, and safety.

PMID- 21733819
TI  - Rapamycin and mTORC1 inhibition in the mouse: skin cancer prevention.
AB  - Therapeutic and preventive effects of rapamycin include reduced risk of
      nonmelanoma skin cancer (NMSC). In this issue of the journal (beginning on page
      1011), Checkley and colleagues report that rapamycin inhibits mTOR complex 1 in
      murine epidermis, thereby inhibiting tumor promotion mediated by tetradecanoyl
      phorbol-13 acetate in association with a strong anti-inflammatory effect.
      Rapamycin is an immunosuppressive drug for preventing graft rejection in organ
      transplant recipients and reduces the risk of NMSC and Kaposi's sarcoma in this
      population, albeit by mechanisms distinct from immunosuppression. Important
      future directions include identifying molecular predictors of rapamycin/rapalog
      sensitivity or resistance (potentially, for example, PI3K pathway alterations and
      KRAS mutations) and combined non-rapalog, mTOR-targeting approaches, all of which
      should increase efficacy and minimize toxicity.

PMID- 21733820
TI  - The BATTLE to personalize lung cancer prevention through reverse migration.
AB  - Agents can enter clinical development for cancer prevention either initially or
      after previous development for a different indication, such as arthritis, with
      both approaches consuming many years of development before an agent is fully
      evaluated for cancer prevention. We propose the following, third approach:
      reverse migration, that is, importing agents, targets, and study designs to
      personalize interventions and concepts developed in advanced cancer to the
      setting of cancer prevention. Importing these "ready-made" features from therapy
      will allow reverse migration to streamline preventive agent development. We
      recently reported the Biomarker-integrated Approaches of Targeted Therapy for
      Lung Cancer Elimination (BATTLE) trial of personalized lung cancer therapy and
      now propose the reverse migration development of personalized lung cancer
      prevention based on the BATTLE model.

PMID- 21733821
TI  - Role of autophagy in cancer prevention.
AB  - Macroautophagy (autophagy hereafter) is a catabolic process by which cells
      degrade intracellular components in lysosomes. This cellular garbage disposal and
      intracellular recycling system maintains cellular homeostasis by eliminating
      superfluous or damaged proteins and organelles and invading microbes and by
      providing substrates for energy generation and biosynthesis in stress. Autophagy
      thus promotes the health of cells and animals and is critical for the
      development, differentiation, and maintenance of cell function and for the host
      defense against pathogens. Deregulation of autophagy is linked to susceptibility
      to various disorders including degenerative diseases, metabolic syndrome, aging,
      infectious diseases, and cancer. Autophagic activity emerges as a critical factor
      in the development and progression of diseases that are associated with increased
      cancer risk as well as in different stages of cancer. Given that cancer is a
      complex process and autophagy exerts its effects in multiple ways, the role of
      autophagy in tumorigenesis is context-dependent. As a cytoprotective survival
      pathway, autophagy prevents chronic tissue damage that can lead to cancer
      initiation and progression. In this setting, stimulation or restoration of
      autophagy may prevent cancer. In contrast, once cancer occurs, many cancer cells
      upregulate basal autophagy and utilize autophagy to enhance fitness and survive
      in the hostile tumor microenvironment. These findings revealed the concept that
      aggressive cancers can be addicted to autophagy for survival. In this setting,
      autophagy inhibition is a therapeutic strategy for established cancers.

PMID- 21733823
TI  - A DNA vaccine against ERBB2 impairs chemical carcinogenesis in random-bred
      hamsters.
AB  - Vaccines against oncoantigens halt early neoplastic lesions in several cancer
      prone, genetically engineered mouse models, whereas their ability to prevent
      chemical carcinogenesis has not been explored. This is a significant issue, as
      exposure to chemical mutagens is responsible for a substantial percentage of
      cancers worldwide. Here, we show that the archetypal oncoantigen ERBB2 is
      transiently overexpressed in Syrian hamsters during the early stages of 7,12
      dimethylbenz[alpha]anthracene (DMBA)-induced oral carcinogenesis. Repeated DNA
      vaccinations against ERBB2 significantly reduce the number, size, and severity of
      oral lesions in a manner directly proportional to the anti-ERBB2 antibody
      response. These results support the prospects of vaccines as a fresh strategy in
      the management of individuals at risk for exposure to defined carcinogenic
      agents.

PMID- 21733822
TI  - Lung cancer chemoprevention with celecoxib in former smokers.
AB  - Ample studies suggest that the cyclooxygenase-2 (COX-2)/prostaglandin E(2)
      (PGE(2)) pathway plays a pivotal role in carcinogenesis and that COX-2 inhibition
      may help prevent lung cancer. Therefore, we conducted a randomized, double-blind,
      placebo-controlled trial of the COX-2-selective inhibitor celecoxib (400 mg bid
      for 6 months) in former-smokers (age >= 45, >= 30 pack-years of smoking, >= 1
      year of sustained abstinence from smoking). We assessed the impact of celecoxib
      on cellular and molecular events associated with lung cancer pathogenesis; the
      primary endpoint was bronchial Ki-67 labeling index (Ki-67 LI) after 6 months of
      treatment. Of 137 randomized subjects, 101 completed both baseline and 6-month
      bronchoscopies and were evaluable for the primary endpoint analysis. The
      beneficial effect on Ki-67 LI was greater in the celecoxib arm (versus placebo)
      in a mixed-effects analysis (P = 0.0006), and celecoxib significantly decreased
      Ki-67 LI by an average of 34%, whereas placebo increased Ki-67 LI by an average
      of 3.8% (P = 0.04; t test). In participants who crossed over to the other study
      arm at 6 months (all of whom had received 6 months of celecoxib at the end of a
      12 months treatment period), the decreases in Ki-67 LI correlated with a
      reduction and/or resolution of lung nodules on computed tomography. Celecoxib
      significantly reduced plasma c-reactive protein and interleukin-6 mRNA and
      protein and increased 15(S)-hydroxy-eicosatetraenoic acid levels in
      bronchoalveolar lavage (BAL) samples. The baseline ratio of COX-2 to 15
      hydroxyprostaglandin dehydrogenase mRNA in BAL cells was a significant predictive
      marker of Ki-67 response to celecoxib (P = 0.002). Our collective findings
      support the continued investigation of celecoxib for lung cancer chemoprevention
      in former smokers at a low risk of cardiovascular disease.

PMID- 21733824
TI  - Decreased prostate cancer-specific survival of men with BRCA2 mutations from
      multiple breast cancer families.
AB  - The role of a germ-line BRCA2 mutation in the development of prostate cancer is
      established, but the clinical presentation linked to outcome for this group of
      men has not been well described. A total of 148 men from 1,423 families were
      ascertained from the kConFab consortium. Each participant met the following
      criteria: (i) a verified case of prostate cancer; (ii) confirmed as either a
      carrier or noncarrier of a family-specific BRCA pathogenic mutation; (iii)
      comprehensive clinical and treatment data were available. Clinical data were
      linked to treatment received and overall survival was analyzed by Kaplan-Meier.
      Prostate cancer in men from breast cancer-prone families has a high risk of
      disease progression, irrespective of mutation status. BRCA2 mutation carriers
      have an increased risk of death and prostate cancer-related death [HR (95% CI)
      4.5 (2.12-9.52), P = 8.9 * 10(-5)] by comparison with noncarriers. Serum PSA
      readings taken prior to diagnosis in 90% of all men, age adjusted, were above
      clinical significance. Following D'Amico risk stratification, 77.5% of BRCA2
      mutation carriers and 58.7% of noncarriers had high-risk disease. BRCA2 mutation
      status was also an independent prognostic indicator of overall survival.
      Furthermore, there was a poor overall survival outcome for both the BRCA2
      mutation carriers and noncarriers given curative-intent treatment. All men in
      breast cancer-prone families are at risk of developing aggressive prostate
      cancer. This information is significant and should be included in discussions
      with genetic counselors and medical professionals when discussing prostate cancer
      treatment options for men in these families, irrespective of mutation status.

PMID- 21733825
TI  - Rapamycin is a potent inhibitor of skin tumor promotion by 12-O
      tetradecanoylphorbol-13-acetate.
AB  - Aberrant activation of phosphoinositide-3-kinase (PI3K)/Akt signaling has been
      implicated in the development and progression of multiple human cancers. During
      the process of skin tumor promotion induced by treatment with the phorbol ester
      12-O-tetradecanoylphorbol-13-acetate (TPA), activation of epidermal Akt occurs as
      well as several downstream effectors of Akt, including the activation of mTORC1.
      Rapamycin, an established mTORC1 inhibitor, was used to further explore the role
      of mTORC1 signaling in epithelial carcinogenesis, specifically during the tumor
      promotion stage. Rapamycin blocked TPA-induced activation of mTORC1 as well as
      several downstream targets. In addition, TPA-induced epidermal hyperproliferation
      and hyperplasia were inhibited in a dose-dependent manner with topical rapamycin
      treatments. Immunohistochemical analyses of the skin from mice in this multiple
      treatment experiment revealed that rapamycin also significantly decreased the
      number of infiltrating macrophages, T cells, neutrophils, and mast cells seen in
      the dermis following TPA treatment. Using a two-stage skin carcinogenesis
      protocol with 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and TPA as the
      promoter, rapamycin (5-200 nmol per mouse given topically 30 minutes prior to
      TPA) exerted a powerful antipromoting effect, reducing both tumor incidence and
      tumor multiplicity. Moreover, topical application of rapamycin to existing
      papillomas induced regression and/or inhibited further growth. Overall, the data
      indicate that rapamycin is a potent inhibitor of skin tumor promotion and suggest
      that signaling through mTORC1 contributes significantly to the process of skin
      tumor promotion. The data also suggest that blocking this pathway either alone or
      in combination with other agents targeting additional pathways may be an
      effective strategy for prevention of epithelial carcinogenesis.

PMID- 21733826
TI  - EarlyCDT-Lung: an immunobiomarker test as an aid to early detection of lung
      cancer.
AB  - Recent publications have reported the technical and clinical validation of
      EarlyCDT-Lung, an autoantibody test which detected elevated autoantibodies in 40%
      of lung cancers at diagnosis. This manuscript reports the results of EarlyCDT
      Lung run on four new (postvalidation) data sets. The following four cohorts of
      patients (n = 574) with newly diagnosed lung cancer were identified: group 1 (n =
      122), 100% small cell lung cancer (SCLC); group 2 (n = 249), 97% non-small cell
      lung cancer (NSCLC); group 3 (n = 122), 100% NSCLC; group 4 (n = 81), 62% NSCLC.
      Serum samples were obtained after diagnosis, prior to any anticancer treatment.
      Autoantibody levels were measured against a panel of six tumor-related antigens
      (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1, and SOX2) in the EarlyCDT-Lung panel and
      previously established cutoffs applied. In groups 2, 3, and 4, patients were
      individually matched by gender, age, and smoking history to a control individual
      with no history of malignant disease. Assay sensitivity was tested in relation to
      cancer type and stage, and in the matched normals to demographic variables. The
      autoantibody panel showed sensitivity/specificity of 57%/n.d (not done) for SCLC
      in group 1, 34%/87% for NSCLC in group 2, 31% and 84% for NSCLC in group 3, and
      35%/89% for NSCLC and 43%/89% for SCLC in group 4. There was no significant
      difference in positivity of EarlyCDT-Lung and different lung cancer stages. These
      studies confirm the value of an autoantibody assay, EarlyCDT-Lung, as an aid to
      detecting lung cancer in patients at high risk of the disease.

PMID- 21733827
TI  - Data supporting a new physiological role for brain apelin in the regulation of
      hypothalamic oxytocin neurons in lactating rats.
AB  - Apelin is a bioactive peptide identified as the endogenous ligand of the human
      orphan G protein-coupled receptor APJ in 1998. The present data show that apelin
      modulates the activity of magnocellular and parvocellular oxytocin (OXY) neurons
      in the lactating rat. A combination of in situ hybridization and
      immunohistochemistry demonstrated the presence of apelin receptor mRNA in
      hypothalamic OXY neurons. Double immunofluorescence labeling then revealed the
      colocalization of apelin with OXY in about 20% of the hypothalamic OXY-positive
      neurons. Intracerebroventricular apelin administration inhibited the activity of
      magnocellular and parvocellular OXY neurons, as shown by measuring the c-fos
      expression in OXY neurons or by direct electrophysiological measurements of the
      electrical activity of these neurons. This effect was correlated with a decrease
      in the amount of milk ejected. Thus, apelin inhibits the activity of OXY neurons
      through a direct action on apelin receptors expressed by these neurons in an
      autocrine and paracrine manner. In conclusion, these findings highlight the
      inhibitory role of apelin as an autocrine/paracrine peptide acting on OXY neurons
      during breastfeeding.

PMID- 21733828
TI  - Androgen suppression-induced stimulation of spermatogonial differentiation in
      juvenile spermatogonial depletion mice acts by elevating the testicular
      temperature.
AB  - Why both testosterone (T) suppression and cryptorchidism reverse the block in
      spermatogonial differentiation in adult mice homozygous for the juvenile
      spermatogonial depletion (jsd) mutation has been a conundrum. To resolve this
      conundrum, we analyzed interrelations between T suppression, testicular
      temperature, and spermatogonial differentiation and used in vitro techniques to
      separate the effects of the two treatments on the spermatogonial differentiation
      block in jsd mice. Temporal analysis revealed that surgical cryptorchidism
      rapidly stimulated spermatogonial differentiation whereas androgen ablation
      treatment produced a delayed and gradual differentiation. The androgen
      suppression caused scrotal shrinkage, significantly increasing the intrascrotal
      temperature. When serum T or intratesticular T (ITT) levels were modulated
      separately in GnRH antagonist-treated mice by exogenous delivery of T or LH,
      respectively, the inhibition of spermatogonial differentiation correlated with
      the serum T and not with ITT levels. Thus, the block must be caused by peripheral
      androgen action. When testicular explants from jsd mice were cultured in vitro at
      32.5 C, spermatogonial differentiation was not observed, but at 37 C significant
      differentiation was evident. In contrast, addition of T to the culture medium did
      not block the stimulation of spermatogonial differentiation at 37 C, and androgen
      ablation with aminoglutethimide and hydroxyflutamide did not stimulate
      differentiation at 32.5 C, suggesting that T had no direct effect on
      spermatogonial differentiation in jsd mice. These data show that elevation of
      temperature directly overcomes the spermatogonial differentiation block in adult
      jsd mice and that T suppression acts indirectly in vivo by causing scrotal
      regression and thereby elevating the testicular temperature.

PMID- 21733829
TI  - Evidence of adrenal failure in aging Dax1-deficient mice.
AB  - Dosage-sensitive sex reversal, adrenal hypoplasia congenita (AHC) critical region
      on the X chromosome, gene 1 (Dax1) is an orphan nuclear receptor essential for
      development and function of the mammalian adrenal cortex and gonads. DAX1 was
      cloned as the gene responsible for X-linked AHC, which is characterized by
      adrenocortical failure necessitating glucocorticoid replacement. Contrary to
      these human data, young mice with genetic Dax1 knockout (Dax1(-/Y)) exhibit
      adrenocortical hyperfunction, consistent with the historic description of Dax1 as
      a transcriptional repressor that inhibits steroidogenic factor 1-dependent
      steroidogenesis. This paradox of molecular function and two apparently opposite
      phenotypes associated with Dax1 deficiency in mice and humans is compounded by
      the recent observations that under certain circumstances, Dax1 can serve as a
      transcriptional activator of steroidogenic factor 1. The recently revealed role
      of Dax1 in embryonic stem cell pluripotency, together with the observation that
      its expression in the adult adrenal is restricted to the subcapsular cortex,
      where presumptive undifferentiated progenitor cells reside, has led us to
      reexamine the phenotype of Dax1(-/Y) mice in order to reconcile the conflicting
      mouse and human data. In this report, we demonstrate that although young Dax1(
      /Y) mice have enhanced steroidogenesis and subcapsular adrenocortical
      proliferation, as these mice age, they exhibit declining adrenal growth,
      decreasing adrenal steroidogenic capacity, and a reversal of their initial
      enhanced hormonal sensitivity. Together with a marked adrenal dysplasia in aging
      mice, these data reveal that both Dax1(-/Y) mice and patients with X-linked AHC
      exhibit adrenal failure that is consistent with adrenocortical subcapsular
      progenitor cell depletion and argue for a significant role of Dax1 in maintenance
      of these cells.

PMID- 21733830
TI  - Antenatal dexamethasone treatment in midgestation reduces system A-mediated
      transport in the late-gestation murine placenta.
AB  - Clinically, approximately 30% of women who receive synthetic glucocorticoids
      (sGC) for risk of preterm labor carry to term. In vitro studies have shown that
      sGC acutely regulate the placental system A amino acid transporter, but there are
      no comparable data in vivo. Hence, the objective of our study was to examine the
      acute [embryonic day (E)15.5] and longer-term (E17.5 and E18.5) consequences of
      midgestation antenatal sGC [dexamethasone (DEX); 0.1 mg/kg on E13.5 and E14.5] on
      placental system A-mediated transfer in the mouse (measured in vivo as maternal
      fetal unidirectional (14)C-methylaminoisobutyric acid transfer per gram of
      placenta). System A transfer and Slc38a mRNA expression significantly increased
      from E12.5 to E18.5 (P < 0.05), corresponding to increased fetal growth. DEX
      treatment had no acute effect at E15.5 or longer-term effect at E17.5 but
      significantly decreased system A-mediated transfer before term (E18.5; P < 0.05)
      in placentae of male and female fetuses. There was no effect of DEX on Slc38a
      gene expression. Administration of DEX in this regime had no effect on birth
      weight. We conclude that sGC treatment in midgestation leads to a substantial
      decrease in placental system A-mediated transport in late gestation, suggesting
      that prenatal sGC therapy may lead to a reduction in availability of neutral
      amino acids to the fetus if gestation persists to term.

PMID- 21733831
TI  - Smooth muscle cell-specific knockout of androgen receptor: a new model for
      prostatic disease.
AB  - Androgen-driven stromal-epithelial interactions play a key role in normal
      prostate development and function as well as in the progression of common
      prostatic diseases such as benign prostatic hyperplasia and prostate cancer.
      However, exactly how, and via which cell type, androgens mediate their effects in
      the adult prostate remains unclear. This study investigated the role for smooth
      muscle (SM) androgen signaling in normal adult prostate homeostasis and function
      using mice in which androgen receptor was selectively ablated from prostatic SM
      cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate
      weight and exhibited histological abnormalities such as hyperplasia,
      inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell
      identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged
      beyond puberty and were not explained by changes in serum hormones. Furthermore,
      in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater
      increase in prostate weight than controls and developed urinary retention. KO
      mice also demonstrated a reduced response to castration compared with controls.
      Together these results demonstrate that prostate SM cells are vital in mediating
      androgen-driven stromal-epithelial interactions in adult mouse prostates,
      determining cell identity and function and limiting hormone-dependent epithelial
      cell proliferation. This novel mouse model provides new insight into the possible
      role for SM androgen action in prostate disease.

PMID- 21733832
TI  - Increased bone formation and bone mass induced by sclerostin antibody is not
      affected by pretreatment or cotreatment with alendronate in osteopenic,
      ovariectomized rats.
AB  - Clinical studies have revealed a blunting of the bone anabolic effects of
      parathyroid hormone treatment in osteoporotic patients in the setting of pre- or
      cotreatment with the antiresorptive agent alendronate (ALN). Sclerostin
      monoclonal antibody (Scl-Ab) is currently under clinical investigation as a new
      potential anabolic therapy for postmenopausal osteoporosis. The purpose of these
      experiments was to examine the influence of pretreatment or cotreatment with ALN
      on the bone anabolic actions of Scl-Ab in ovariectomized (OVX) rats. Ten-month
      old osteopenic OVX rats were treated with ALN or vehicle for 6 wk, before the
      start of Scl-Ab treatment. ALN-pretreated OVX rats were switched to Scl-Ab alone
      or to a combination of ALN and Scl-Ab for another 6 wk. Vehicle-pretreated OVX
      rats were switched to Scl-Ab or continued on vehicle to serve as controls. Scl-Ab
      treatment increased areal bone mineral density, volumetric bone mineral density,
      trabecular and cortical bone mass, and bone strength similarly in OVX rats
      pretreated with ALN or vehicle. Serum osteocalcin and bone formation rate on
      trabecular, endocortical, and periosteal surfaces responded similarly to Scl-Ab
      in ALN or vehicle-pretreated OVX rats. Furthermore, cotreatment with ALN did not
      have significant effects on the increased bone formation, bone mass, and bone
      strength induced by Scl-Ab in the OVX rats that were pretreated with ALN. These
      results indicate that the increases in bone formation, bone mass, and bone
      strength with Scl-Ab treatment were not affected by pre- or cotreatment with ALN
      in OVX rats with established osteopenia.

PMID- 21733833
TI  - Exploring treatment attendance and its relationship to outcome in a randomized
      controlled trial of treatment for alcohol problems: secondary analysis of the UK
      Alcohol Treatment Trial (UKATT).
AB  - AIMS: To identify client characteristics that predict attendance at treatment
      sessions and to investigate the effect of attendance on outcomes using data from
      the UK Alcohol Treatment Trial. METHODS: Logistic regression was used to
      determine whether there were characteristics that could predict attendance and
      then continuation in treatment. Linear regression was used to explore the effects
      of treatment attendance on outcomes. RESULTS: There were significant positive
      relationships between treatment attendance and outcomes at Month 3. At Month 12,
      these relationships were only significant for dependence and alcohol problems for
      those randomized to motivational enhancement therapy (MET). There were
      significant differences between groups in attendance, with MET clients more
      likely to attend than clients allocated to social behaviour and network therapy
      (SBNT). MET clients were also more likely to attend all sessions (three sessions)
      compared with SBNT (eight sessions). MET clients with larger social networks and
      those with confidence in their ability not to drink excessively were more likely
      to attend. SBNT clients with greater motivation to change and those with more
      negative short-term alcohol outcome expectancies were more likely to attend. No
      significant predictors were found for retention in treatment for MET. For those
      receiving SBNT, fewer alcohol problems were associated with continuation in
      treatment. CONCLUSION: Attending more sessions was associated with better
      outcomes. An interpretation of these findings is that, to improve outcomes,
      methods should be developed and used to increase attendance rates. Different
      characteristics were identified that predicted attendance and continuation in
      treatment for MET and SBNT.

PMID- 21733834
TI  - Heavy episodic drinking in Europe: a cross section study in primary care in six
      European countries.
AB  - AIMS: We examined the prevalence of heavy episodic drinking in general practice
      attenders who were non-hazardous drinkers, the associated risk factors and the
      outcome over 6 months. METHODS: Consecutive attenders aged 18-75 were recruited
      from the UK, Spain, Slovenia, Estonia, the Netherlands and Portugal and followed
      up after 6 months. Data were collected on alcohol use using the Alcohol Use
      Disorder Identification test (at recruitment and 6 months) and risk factors for
      heavy episodic alcohol use at recruitment. RESULTS: The prevalence of heavy
      episodic drinking in non-hazardous drinkers was 4.5% across Europe [lowest in
      Portugal (1.5%); highest Netherlands (8.4%)]. It was less frequent in Spain,
      Slovenia, Estonia and Portugal compared with the UK and Netherlands. It was
      higher in men [odd ratio (OR) 4.4, 95% confidence interval (CI) 3.3, 5.9], people
      between 18 and 29 years of age, those employed (OR 1.8, 95% CI 1.3, 2.6) and
      those using recreational drugs (OR 2.1, 95% CI 1.4, 3.3). It was lower in people
      with existing DSMIV major depression (OR 0.54, 95% CI 0.31, 0.96). Heavy episodic
      drinkers were more likely to become hazardous drinkers at 6 months (male: OR 7.2,
      95% CI 4.1, 12.7; female: OR 9.4, 95% CI 4.3, 20.6). CONCLUSION: Women and men in
      the UK, men in the Netherlands and younger people in all countries are at the
      greatest risk of exhibiting heavy episodic drinking behaviours even in the
      absence of hazardous alcohol use. There is hence an urgent need for general
      practitioners to consider early detection and management of heavy episodic
      drinking behaviour in this population.

PMID- 21733835
TI  - Exposure to alcohol advertising and alcohol consumption among Australian
      adolescents.
AB  - AIMS: Underage drinking is a major problem in Australia and may be influenced by
      exposure to alcohol advertising. The objective of the present study was to
      collect data on 12-17 year old Australian adolescents' exposure to different
      types of alcohol advertising and examine the association between exposure to
      advertising and alcohol consumption. METHODS: A cross-sectional survey of 1113
      adolescents aged 12-17 years recruited with a variety of methods to gain a cross
      section of participants across metropolitan, regional and rural New South Wales
      (including independent schools, mall intercepts and online). Participants
      answered a series of questions assessing adolescents' exposure to alcohol
      advertising across eight media (including television, Internet and point-of
      sale). Alcohol consumption was assessed using three questions (initiation, recent
      consumption and frequency of consumption in the previous 12 months). RESULTS: The
      majority indicated that they had been exposed to alcohol advertisements on
      television, in newspapers and magazines, on the Internet, on billboards/posters
      and promotional materials and in bottleshops, bars and pubs; exposure to some of
      these types of alcohol advertisements was associated with increased alcohol
      consumption, with differences by age and gender. CONCLUSION: The results are
      consistent with studies from other countries and suggest that exposure to alcohol
      advertisements among Australian adolescents is strongly associated with drinking
      patterns. Given current high levels of drinking among Australian youth, these
      findings suggest the need to address the high levels of young people's exposure
      to alcohol advertising.

PMID- 21733836
TI  - Evaluation of myocyte proliferation in alcoholic cardiomyopathy: telomerase
      enzyme activity (TERT) compared with Ki-67 expression.
AB  - AIMS: Although the human heart was classically considered a terminal organ,
      recent studies have reported a myocyte proliferation response versus some
      aggressions. Excessive ethanol consumption induces development of cardiomyopathy
      (CMP) through myocyte apoptosis. We evaluated myocyte proliferation response in
      the heart of chronic alcoholic donors with telomerase activity (telomerase
      reverse transcriptase (TERT)) compared with Ki-67 nuclear expression. METHODS:
      Heart samples were prospectively obtained from organ donors on life support. We
      included donors with (1) high lifetime alcohol consumption (n = 15), (2)
      longstanding hypertension (n = 14), (3) other causes of CMP (valve, coronary or
      idiopathic) (n = 8) and (4) previously healthy donors (n = 6). Groups 2 and 3
      were subdivided according to the presence of CMP. Evaluation comprised parameters
      of ethanol consumption, left ventricular function by chest X-ray and 2D
      echocardiography, and histology and immunohistochemical studies. Myocyte
      proliferation was evaluated using an assay for Ki-67 expression and measuring
      telomerase gene activity by real-time PCR. RESULTS: Forty-three donors were
      included in the study, 35 having CMP. Nuclear Ki-67 activity was low in healthy
      controls and significantly increased in the other groups, mainly in those with
      CMP. Alcoholics with CMP had a non-significantly lower proliferation response
      than the other CMP groups. No proliferation activity was detected with TERT in
      any case. CONCLUSION: Heart Ki-67 proliferation activity increases in organ
      donors with CMP, independently of its origin. Alcoholics presented non
      significant lower myocyte proliferation capacity compared with the other groups
      of CMP. TERT activity was not a useful marker of proliferation in this model. Ki
      67 is a better procedure to evaluate proliferation than TERT expression in
      alcohol-induced heart damage.

PMID- 21733837
TI  - 1alpha,25(OH)2-vitamin D and a nongenomic vitamin D analogue inhibit ultraviolet
      radiation-induced skin carcinogenesis.
AB  - Exposure to ultraviolet radiation (UVR) can lead to a range of deleterious
      responses in the skin. An important form of damage is the DNA photolesion
      cyclobutane pyrimidine dimer (CPD). CPDs can be highly mutagenic if not repaired
      prior to cell division and can lead to UV-induced immunosuppression, making them
      potentially carcinogenic. UVR exposure also produces vitamin D, a prehormone.
      Different shapes of the steroid hormone 1alpha,25-dihydroxyvitamin D3
      [1,25(OH)2D3] can produce biological responses through binding either to its
      cognate nuclear receptor (VDR) to regulate gene transcription or to the VDR
      associated with plasma membrane caveolae to produce, via signal transduction,
      nongenomic physiologic responses. Here, we show that both 1,25(OH)2D3 and
      1alpha,25(OH)2-lumisterol (JN), a conformationally restricted analogue that can
      generate only nongenomic responses, are effective inhibitors of UV damage in an
      immunocompetent mouse (Skh:hr1) model susceptible to UV-induced tumors. Both
      1,25(OH)2D3 and JN significantly reduced UVR-induced CPD, apoptotic sunburn
      cells, and immunosuppression. Furthermore, these compounds inhibited skin tumor
      development, both papillomas and squamous cell carcinomas, in these mice. The
      observed reduction of these UV-induced effects by 1,25(OH)2D3 and JN suggests a
      role for these compounds in prevention against skin carcinogenesis. To the best
      of our knowledge, this is the first comprehensive report of an in vivo long-term
      biological response generated by chronic dosing with a nongenomic-selective
      vitamin D steroid.

PMID- 21733838
TI  - Prevention of colitis-associated colorectal cancer with 8-hydroxydeoxyguanosine.
AB  - Colitis-associated cancer (CAC) is one of clear examples of inflammation
      carcinogenesis sequence, by which the strict control of colitis with potent anti
      inflammatory or antioxidative agent offers the chance of cancer prevention.
      Supported with the facts that Rac1 binds and activates STAT3, which are
      significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but
      8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically
      can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in
      various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX
      NF-kappaB pathway by exogenous 8-OHdG administration may ameliorate inflammatory
      signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC.
      Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can
      alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to
      ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route
      daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS
      induced colitis as well as various inflammatory mediators such as TNF-alpha, IL
      6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention
      effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS
      for 1 week, after which 8-OHdG-containing diets were given for 20 weeks. As
      results, mice that consumed 8-OHdG-containing diet significantly reduced both
      tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level
      were significantly attenuated in the 8-OHdG-treated group. Significantly
      decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix
      metalloproteinasess, COX-2, NOX4, and beta-catenin nuclear accumulation were
      responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we
      clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC.

PMID- 21733839
TI  - The trypanocidal drug suramin and other trypan blue mimetics are inhibitors of
      pyruvate kinases and bind to the adenosine site.
AB  - Ehrlich's pioneering chemotherapeutic experiments published in 1904 (Ehrlich, P.,
      and Shiga, K. (1904) Berlin Klin. Wochenschrift 20, 329-362) described the
      efficacy of a series of dye molecules including trypan blue and trypan red to
      eliminate trypanosome infections in mice. The molecular structures of the dyes
      provided a starting point for the synthesis of suramin, which was developed and
      used as a trypanocidal drug in 1916 and is still in clinical use. Despite the
      biological importance of these dye-like molecules, the mode of action on
      trypanosomes has remained elusive. Here we present crystal structures of suramin
      and three related dyes in complex with pyruvate kinases from Leishmania mexicana
      or from Trypanosoma cruzi. The phenyl sulfonate groups of all four molecules
      (suramin, Ponceau S, acid blue 80, and benzothiazole-2,5-disulfonic acid) bind in
      the position of ADP/ATP at the active sites of the pyruvate kinases (PYKs). The
      binding positions in the two different trypanosomatid PYKs are nearly identical.
      We show that suramin competitively inhibits PYKs from humans (muscle, tumor, and
      liver isoenzymes, K(i) = 1.1-17 MUM), T. cruzi (K(i) = 108 MUM), and L. mexicana
      (K(i) = 116 MUM), all of which have similar active sites. Synergistic effects
      were observed when examining suramin inhibition in the presence of an allosteric
      effector molecule, whereby IC(50) values decreased up to 2-fold for both
      trypanosomatid and human PYKs. These kinetic and structural analyses provide
      insight into the promiscuous inhibition observed for suramin and into the mode of
      action of the dye-like molecules used in Ehrlich's original experiments.

PMID- 21733840
TI  - Structural and functional studies on the N-terminal domain of the Shigella type
      III secretion protein MxiG.
AB  - MxiG is a single-pass membrane protein that oligomerizes within the inner
      membrane ring of the Shigella flexneri type III secretion system (T3SS). The MxiG
      N-terminal domain (MxiG-N) is the predominant cytoplasmic structure; however, its
      role in T3SS assembly and secretion is largely uncharacterized. We have
      determined the solution structure of MxiG-N residues 6-112 (MxiG-N(6-112)),
      representing the first published structure of this T3SS domain. The structure
      shows strong structural homology to forkhead-associated (FHA) domains.
      Canonically, these cell-signaling modules bind phosphothreonine (Thr(P)) via
      highly conserved residues. However, the putative phosphate-binding pocket of MxiG
      N(6-112) does not align with other FHA domain structures or interact with Thr(P).
      Furthermore, mutagenesis of potential phosphate-binding residues has no effect on
      S. flexneri T3SS assembly and function. Therefore, MxiG-N has a novel function
      for an FHA domain. Positioning of MxiG-N(6-112) within the EM density of the S.
      flexneri needle complex gives insight into the ambiguous stoichiometry of the
      T3SS, supporting models with 24 MxiG subunits in the inner membrane ring.

PMID- 21733841
TI  - Molecular basis for the unique role of the AAA+ chaperone ClpV in type VI protein
      secretion.
AB  - Ring-forming AAA(+) ATPases act in a plethora of cellular processes by remodeling
      macromolecules. The specificity of individual AAA(+) proteins is achieved by
      direct or adaptor-mediated association with substrates via distinct recognition
      domains. We investigated the molecular basis of substrate interaction for Vibrio
      cholerae ClpV, which disassembles tubular VipA/VipB complexes, an essential step
      of type VI protein secretion and bacterial virulence. We identified the ClpV
      recognition site within VipB, showed that productive ClpV-VipB interaction
      requires the oligomeric state of both proteins, solved the crystal structure of a
      ClpV N-domain-VipB peptide complex, and verified the interaction surface by
      mutant analysis. Our results show that the substrate is bound to a hydrophobic
      groove, which is formed by the addition of a single alpha-helix to the core N
      domain. This helix is absent from homologous N-domains, explaining the unique
      substrate specificity of ClpV. A limited interaction surface between both
      proteins accounts for the dramatic increase in binding affinity upon ATP-driven
      ClpV hexamerization and VipA/VipB tubule assembly by coupling multiple weak
      interactions. This principle ensures ClpV selectivity toward the VipA/VipB
      macromolecular complex.

PMID- 21733842
TI  - Kinetic and chemical mechanisms of homocitrate synthase from Thermus
      thermophilus.
AB  - The homocitrate synthase from Thermus thermophilus (TtHCS) is a metal-activated
      enzyme with either Mg(2+) or Mn(2+) capable of serving as the divalent cation.
      The enzyme exhibits a sequential kinetic mechanism. The mechanism is steady state
      ordered with alpha-ketoglutarate (alpha-Kg) binding prior to acetyl-CoA (AcCoA)
      with Mn(2+), whereas it is steady state random with Mg(2+), suggesting a
      difference in the competence of the E.Mn.alpha-Kg.AcCoA and E.Mg.alpha-Kg.AcCoA
      complexes. The mechanism is supported by product and dead-end inhibition studies.
      The primary isotope effect obtained with deuterioacetylCoA (AcCoA-d(3)) in the
      presence of Mg(2+) is unity (value 1.0) at low concentrations of AcCoA, whereas
      it is 2 at high concentrations of AcCoA. Data suggest the presence of a slow
      conformational change induced by binding of AcCoA that accompanies deprotonation
      of the methyl group of AcCoA. The solvent kinetic deuterium isotope effect is
      also unity at low AcCoA, but is 1.7 at high AcCoA, consistent with the proposed
      slow conformational change. The maximum rate is pH independent with either Mg(2+)
      or Mn(2+) as the divalent metal ion, whereas V/K(alpha-Kg) (with Mn(2+))
      decreases at low and high pH giving pK values of about 6.5 and 8.0. Lysine is a
      competitive inhibitor that binds to the active site of TtHCS, and shares some of
      the same binding determinants as alpha-Kg. Lysine binding exhibits negative
      cooperativity, indicating cross-talk between the two monomers of the TtHCS dimer.
      Data are discussed in terms of the overall mechanism of TtHCS.

PMID- 21733843
TI  - Molecular insights into DNA polymerase deterrents for ribonucleotide insertion.
AB  - DNA polymerases can misinsert ribonucleotides that lead to genomic instability.
      DNA polymerase beta discourages ribonucleotide insertion with the backbone
      carbonyl of Tyr-271; alanine substitution of Tyr-271, but not Phe-272, resulted
      in a >10-fold loss in discrimination. The Y271A mutant also inserted
      ribonucleotides more efficiently than wild type on a variety of ribonucleoside
      (rNMP)-containing DNA substrates. Substituting Mn(2+) for Mg(2+) decreased sugar
      discrimination for both wild-type and mutant enzymes primarily by increasing the
      affinity for rCTP. This facilitated crystallization of ternary substrate
      complexes of both the wild-type and Y271A mutant enzymes. Crystallographic
      structures of Y271A- and wild type-substrate complexes indicated that rCTP is
      well accommodated in the active site but that O2' of rCTP and the carbonyl oxygen
      of Tyr-271 or Ala-271 are unusually close (~2.5 and 2.6 A, respectively).
      Structure-based modeling indicates that the local energetic cost of positioning
      these closely spaced oxygens is ~2.2 kcal/mol for the wild-type enzyme. Because
      the side chain of Tyr-271 also hydrogen bonds with the primer terminus, loss of
      this interaction affects its catalytic positioning. Our results support a model
      where DNA polymerase beta utilizes two strategies, steric and geometric, with a
      single protein residue to deter ribonucleotide insertion.

PMID- 21733844
TI  - Glycosylation increases the thermostability of human aquaporin 10 protein.
AB  - Human aquaporin10 (hAQP10) is a transmembrane facilitator of both water and
      glycerol transport in the small intestine. This aquaglyceroporin is located in
      the apical membrane of enterocytes and is believed to contribute to the passage
      of water and glycerol through these intestinal absorptive cells. Here we
      overproduced hAQP10 in the yeast Pichia pastoris and observed that the protein is
      glycosylated at Asn-133 in the extracellular loop C. This finding confirms one of
      three predicted glycosylation sites for hAQP10, and its glycosylation is unique
      for the human aquaporins overproduced in this host. Nonglycosylated protein was
      isolated using both glycan affinity chromatography and through mutating
      asparagine 133 to a glutamine. All three forms of hAQP10 where found to
      facilitate the transport of water, glycerol, erythritol, and xylitol, and
      glycosylation had little effect on functionality. In contrast, glycosylated
      hAQP10 showed increased thermostability of 3-6  degrees C compared with the
      nonglycosylated protein, suggesting a stabilizing effect of the N-linked glycan.
      Because only one third of hAQP10 was glycosylated yet the thermostability
      titration was mono-modal, we suggest that the presence of at least one
      glycosylated protein within each tetramer is sufficient to convey an enhanced
      structural stability to the remaining hAQP10 protomers of the tetramer.

PMID- 21733845
TI  - Structural basis of digoxin that antagonizes RORgamma t receptor activity and
      suppresses Th17 cell differentiation and interleukin (IL)-17 production.
AB  - The retinoic acid-related orphan nuclear receptor gammat (RORgammat)/RORgamma2 is
      well known as a master regulator of interleukin 17 (IL-17)-producing helper T
      (Th17) cell development. To develop a therapeutic agent against Th17-mediated
      autoimmune diseases, we screened chemical compounds and successfully found that
      digoxin inhibited IL-17 production. Further studies revealed that digoxin bound
      to the ligand binding domain of RORgammat and suppressed Th17 differentiation
      without affecting Th1 differentiation. To better understand the structural basis
      for the inhibitory activity of digoxin, we determined the crystal structure of
      the RORgammat ligand-binding domain in complex with digoxin at 2.2 A resolution.
      The structure reveals that digoxin binds to the ligand-binding pocket protruding
      between helices H3 and H11 from the pocket. In addition, digoxin disrupts the key
      interaction important for the agonistic activity, resulting in preventing the
      positioning of helix H12 in the active conformation, thus antagonizing
      coactivator interaction. Functional studies demonstrated that digoxin inhibited
      RORgammat activity and decreased IL-17 production but not RORalpha activity.
      Digoxin inhibited IL-17 production in CD4(+) T cells from experimental autoimmune
      encephalomyelitis mice. Our data indicates that RORgammat is a promising
      therapeutic target for Th17-derived autoimmune diseases and our structural data
      will help to design novel RORgammat antagonists.

PMID- 21733846
TI  - WNK2 kinase is a novel regulator of essential neuronal cation-chloride
      cotransporters.
AB  - NKCC1 and KCC2, related cation-chloride cotransporters (CCC), regulate cell
      volume and gamma-aminobutyric acid (GABA)-ergic neurotranmission by modulating
      the intracellular concentration of chloride [Cl(-)]. These CCCs are oppositely
      regulated by serine-threonine phosphorylation, which activates NKCC1 but inhibits
      KCC2. The kinase(s) that performs this function in the nervous system are not
      known with certainty. WNK1 and WNK4, members of the WNK (with no lysine [K])
      kinase family, either directly or via the downstream SPAK/OSR1 Ste20-type
      kinases, regulate the furosemide-sensitive NKCC2 and the thiazide-sensitive NCC,
      kidney-specific CCCs. What role the novel WNK2 kinase plays in this regulatory
      cascade, if any, is unknown. Here, we show that WNK2, unlike other WNKs, is not
      expressed in kidney; rather, it is a neuron-enriched kinase primarily expressed
      in neocortical pyramidal cells, thalamic relay cells, and cerebellar granule and
      Purkinje cells in both the developing and adult brain. Bumetanide-sensitive and
      Cl(-)-dependent (86)Rb(+) uptake assays in Xenopus laevis oocytes revealed that
      WNK2 promotes Cl(-) accumulation by reciprocally activating NKCC1 and inhibiting
      KCC2 in a kinase-dependent manner, effectively bypassing normal tonicity
      requirements for cotransporter regulation. TiO(2) enrichment and tandem mass
      spectrometry studies demonstrate WNK2 forms a protein complex in the mammalian
      brain with SPAK, a known phosphoregulator of NKCC1. In this complex, SPAK is
      phosphorylated at Ser-383, a consensus WNK recognition site. These findings
      suggest a role for WNK2 in the regulation of CCCs in the mammalian brain, with
      implications for both cell volume regulation and/or GABAergic signaling.

PMID- 21733847
TI  - Structural and functional insights into DR2231 protein, the MazG-like nucleoside
      triphosphate pyrophosphohydrolase from Deinococcus radiodurans.
AB  - Deinococcus radiodurans is among the very few bacterial species extremely
      resistant to ionizing radiation, UV light, oxidizing agents, and cycles of
      prolonged desiccation. The proteome of D. radiodurans reflects the evolutionary
      pressure exerted by chronic exposure to (nonradioactive) forms of DNA and protein
      damage. A clear example of this adaptation is the overrepresentation of protein
      families involved in the removal of non-canonical nucleoside triphosphates (NTPs)
      whose incorporation into nascent DNA would promote mutagenesis and DNA damage.
      The three-dimensional structure of the DR2231 protein has been solved at 1.80 A
      resolution. This protein had been classified as an all-alpha-helical MazG-like
      protein. The present study confirms that it holds the basic structural module
      characteristic of the MazG superfamily; two helices form a rigid domain, and two
      helices form a mobile domain and connecting loops. Contrary to what is known of
      MazG proteins, DR2231 protein shows a functional affinity with dUTPases.
      Enzymatic and isothermal calorimetry assays have demonstrated high specificity
      toward dUTP but an inability to hydrolyze dTTP, a typical feature of dUTPases. Co
      crystallization with the product of hydrolysis, dUMP, in the presence of
      magnesium or manganese cations, suggests similarities with the dUTP/dUDP
      hydrolysis mechanism reported for dimeric dUTPases. The genome of D. radiodurans
      encodes for all enzymes required for dTTP synthesis from dCMP, thus bypassing the
      need of a dUTPase. We postulate that DR2231 protein is not essential to D.
      radiodurans and rather performs "house-cleaning" functions within the framework
      of oxidative stress response. We further propose DR2231 protein as an
      evolutionary precursor of dimeric dUTPases.

PMID- 21733848
TI  - Stalled proteasomes are directly relieved by P97 recruitment.
AB  - The 26 S proteasome is the eukaryotic protease responsible for the degradation of
      most cellular proteins. As such it accommodates the ability to function under
      diverse conditions that the cell may encounter. This function is supported by
      various adaptors that modulate various aspects in protein degradation, these
      include regulation of substrate delivery, deubiquitination, unfolding, and 20 S
      gate dilation. Here we show a new functional complex between the P97 and the
      proteasome that is assembled in response to proteasomal impairment. This entails
      P97 binding to the 26 S proteasome via the 19 S particle thereby forming an
      additional hexameric ATPase ring to relieve repression. P97-bound proteasomes
      showed selective binding toward the Npl4-ufd1 P97 co-factors, indicating a unique
      cellular role for P97 binding to proteasomes. P97-bound proteasomes display
      enhanced activity, showing a relief in proteolysis impairment. Our findings place
      P97 directly in non-ERAD proteasomal functions and establish a new checkpoint in
      UPS impairment. The ability to modulate proteasome activity and properly respond
      to protein misfolding, is of great importance in cellular regulation.

PMID- 21733849
TI  - Glucocorticoid elevation of dexamethasone-induced gene 2 (Dig2/RTP801/REDD1)
      protein mediates autophagy in lymphocytes.
AB  - Glucocorticoid hormones, including dexamethasone, induce apoptosis in lymphocytes
      and consequently are used clinically as chemotherapeutic agents in many
      hematologic malignancies. Dexamethasone also induces autophagy in lymphocytes,
      although the mechanism is not fully elucidated. Through gene expression analysis,
      we found that dexamethasone induces the expression of a gene encoding a stress
      response protein variously referred to as Dig2, RTP801, or REDD1. This protein is
      reported to inhibit mammalian target of rapamycin (mTOR) signaling. Because
      autophagy is one outcome of mTOR inhibition, we investigated the hypothesis that
      Dig2/RTP801/REDD1 elevation contributes to autophagy induction in dexamethasone
      treated lymphocytes. In support of this hypothesis, RNAi-mediated suppression of
      Dig2/RTP801/REDD1 reduces mTOR inhibition and autophagy in glucocorticoid-treated
      lymphocytes. We observed similar results in Dig2/Rtp801/Redd1 knock-out murine
      thymocytes treated with dexamethasone. Dig2/RTP801/REDD1 knockdown also leads to
      increased levels of dexamethasone-induced cell death, suggesting that
      Dig2/RTP801/REDD1-mediated autophagy promotes cell survival. Collectively, these
      findings demonstrate for the first time that elevation of Dig2/RTP801/REDD1
      contributes to the induction of autophagy.

PMID- 21733850
TI  - K-Cl cotransporter gene expression during human and murine erythroid
      differentiation.
AB  - The K-Cl cotransporter (KCC) regulates red blood cell (RBC) volume, especially in
      reticulocytes. Western blot analysis of RBC membranes revealed KCC1, KCC3, and
      KCC4 proteins in mouse and human cells, with higher levels in reticulocytes. KCC
      content was higher in sickle versus normal RBC, but the correlation with
      reticulocyte count was poor, with inter-individual variability in KCC isoform
      ratios. Messenger RNA for each isoform was measured by real time RT-quantitative
      PCR. In human reticulocytes, KCC3a mRNA levels were consistently the highest, 1-7
      fold higher than KCC4, the second most abundant species. Message levels for KCC1
      and KCC3b were low. The ratios of KCC RNA levels varied among individuals but
      were similar in sickle and normal RBC. During in vivo maturation of human
      erythroblasts, KCC3a RNA was expressed consistently, whereas KCC1 and KCC3b
      levels declined, and KCC4 message first increased and then decreased. In mouse
      erythroblasts, a similar pattern for KCC3 and KCC1 expression during in vivo
      differentiation was observed, with low KCC4 RNA throughout despite the presence
      of KCC4 protein in mature RBC. During differentiation of mouse erythroleukemia
      cells, protein levels of KCCs paralleled increasing mRNA levels. Functional
      properties of KCCs expressed in HEK293 cells were similar to each other and to
      those in human RBC. However, the anion dependence of KCC in RBC resembled most
      closely that of KCC3. The results suggest that KCC3 is the dominant isoform in
      erythrocytes, with variable expression of KCC1 and KCC4 among individuals that
      could result in modulation of KCC activity.

PMID- 21733851
TI  - Vesicle-associated membrane protein 8 (VAMP8) is a SNARE (soluble N
      ethylmaleimide-sensitive factor attachment protein receptor) selectively required
      for sequential granule-to-granule fusion.
AB  - Compound exocytosis is found in many cell types and is the major form of
      regulated secretion in acinar and mast cells. Its key characteristic is the
      homotypic fusion of secretory granules. These then secrete their combined output
      through a single fusion pore to the outside. The control of compound exocytosis
      remains poorly understood. Although soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (SNAREs) such as syntaxin 2, SNAP23 (synaptosome
      associated protein of 23 kDa), and SNAP25 have been suggested to play a role,
      none has been proven. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE
      first associated with endocytic processes but more recently has been suggested as
      an R-SNARE in regulated exocytosis. Secretion in acinar cells is reduced when
      VAMP8 function is inhibited and is less in VAMP8 knock-out mice. Based on
      electron microscopy experiments, it was suggested that VAMP8 may be involved in
      compound exocytosis. Here we have tested the hypothesis that VAMP8 controls
      homotypic granule-to-granule fusion during sequential compound exocytosis. We use
      a new assay to distinguish primary fusion events (fusion with the cell membrane)
      from secondary fusion events (granule-granule fusion). Our data show the
      pancreatic acinar cells from VAMP8 knock-out animals have a specific reduction in
      secondary granule fusion but that primary granule fusion is unaffected.
      Furthermore, immunoprecipitation experiments show syntaxin 2 association with
      VAMP2, whereas syntaxin 3 associates with VAMP8. Taken together our data indicate
      that granule-to-granule fusion is regulated by VAMP8 containing SNARE complexes
      distinct from those that regulate primary granule fusion.

PMID- 21733853
TI  - Pregnancy outcomes in 188 French cases of prenatally diagnosed Klinefelter
      syndrome.
AB  - BACKGROUND: Klinefelter syndrome (KS), a common sex chromosome aneuploidy
      (47,XXY) is diagnosed prenatally with an incidence of 0.15%. The diagnosis is
      generally incidental, since there are no typical malformations on ultrasound
      (US). Once detected, genetic counseling is often difficult and the parents'
      decision to continue or terminate the pregnancy is greatly dependent on the
      amount and nature of the information provided. We sought to assess the pregnancy
      outcomes (i.e. continuation versus termination) and the influence of
      multidisciplinary centers for prenatal diagnosis on parental decisions in cases
      of KS. METHODS: From 1985 to 2009, 188 prenatal diagnoses of KS were made by 11
      participating laboratories in mainland France. In each case, the karyotype
      indication, parental ages, year of prenatal testing, sampling procedure,
      karyotype, associated US findings and outcome were recorded. RESULTS AND
      CONCLUSIONS: The pregnancy termination rate declined markedly over time, from
      46.9% before 1997 to 11.6% thereafter, in line with the introduction of new
      legislation on prenatal diagnosis for medical reasons and, more specifically, the
      creation of multidisciplinary prenatal diagnosis centers. However, an additional
      microdeletion in one KS infant who exhibited echogenic bowel on US was
      unfortunately diagnosed postnatally. This raises the question as to whether array
      comparative genomic hybridization should be prenatally advised when US
      abnormalities are detected, in line with advice for fetuses with a normal
      karyotype.

PMID- 21733854
TI  - DNA damage induces down-regulation of PEPCK and G6P gene expression through
      degradation of PGC-1alpha.
AB  - Hepatic gluconeogenesis plays a crucial role in glucose homeostasis. Although it
      is well established that various cellular processes are modulated by DNA damage,
      whether the DNA damage signaling pathway regulates gluconeogenesis has not yet
      been studied. In this study, we found that mRNA levels of phosphoenolpyruvate
      carboxykinase (PEPCK) and glucose-6-phosphatase (G6P), key enzymes for
      gluconeogenesis, were dramatically decreased upon IR- and UV-irradiation. PEPCK
      and G6P promoter activities were also suppressed by IR- and UV-irradiation,
      suggesting that PEPCK and G6P gene transcription are down-regulated upon DNA
      damage. We also found that the protein level of PGC-1alpha, which is a critical
      transcription factor for PEPCK gene expression, is decreased upon UV-irradiation.
      The decreased PGC-1alpha protein level was abolished by MG132, a potent
      proteasome inhibitor, suggesting that PGC-1alpha is degraded through the
      ubiquitin-proteasome pathway upon UV-irradiation. These results reveal a novel
      link between glucose metabolism and the DNA damage signaling pathway and suggest
      a possible role for PEPCK and G6P in the DNA damage response.

PMID- 21733855
TI  - A cotton gene encoding novel MADS-box protein is preferentially expressed in
      fibers and functions in cell elongation.
AB  - Cotton fibers, as natural fibers, are widely used in the textile industry in the
      world. In order to find genes involved in fiber development, a cDNA (designated
      as GhMADS11) encoding a novel MADS protein with 151 amino acid residues was
      isolated from cotton fiber cDNA library. The deduced protein shares high
      similarity with Arabidopsis AP1 and AGL8 in MADS domain. However, the GhMADS11
      protein (being absent of the partial K-domain and normal C-terminus) is shorter
      than AP1 and AGL8 by the reason of gene frameshift mutation during evolution. The
      experimental results revealed that GhMADS11 was not a transcriptional activator,
      and it did not form homodimer. GhMADS11 transcripts were specifically accumulated
      in elongating fibers, but no or very low signals of its expression were detected
      in other tissues of cotton. Overexpression of GhMADS11 in fission yeast promotes
      atypical cell elongation by 1.4-2.0-fold. Furthermore, morphological analysis
      indicated that the transformed cells expressing GhMADS11m, a MIKC-type derivative
      of GhMADS11 by the site-directed mutation, displayed the same phenotype as that
      of the transformed cells with GhMADS11. The concurrence of these data sets
      suggested that GhMADS11 protein may function in fiber cell elongation, and its
      MADS domain and partial K-domain are sufficient for this function.

PMID- 21733856
TI  - Radiation dose measurement in gastrointestinal studies.
AB  - Barium studies investigations (barium swallow, barium meal and barium enema) are
      the basic routine radiological examination, where barium sulphate suspension is
      introduced to enhance image contrast of gastrointestinal tracts. The aim of this
      study was to quantify the patients' radiation doses during barium studies and to
      estimate the organ equivalent dose and effective dose with those procedures. A
      total of 33 investigations of barium studies were measured by using
      thermoluminescence dosemeters. The result showed that the patient entrance
      surface doses were 12.6 +/- 10, 44.5 +/- 49 and 35.7 +/- 50 mGy for barium
      swallow, barium meal, follow through and enema, respectively. Effective doses
      were 0.2, 0.35 and 1.4 mSv per procedure for barium swallow, meal and enema
      respectively. Radiation doses were comparable with the previous studies. A
      written protocol for each procedure will reduce the inter-operator variations and
      will help to reduce unnecessary exposure.

PMID- 21733857
TI  - Regulation of radiation protection of the patient: how and how much, the current
      Belgian situation.
AB  - Regulation of radiation protection has always been a cornerstone to protect the
      patient when exposed to ionising radiation. However, large differences exist
      between the implementation of international approved recommendations. Even when a
      well-established supra-national legislative format exists, further translation is
      always adapted to a suitable level of the medical sector in a country. Actual
      trends are given for the Belgian situation, where the legislation on radiation
      protection in medicine is currently under revision.

PMID- 21733858
TI  - Is hair loss a reality in neuro-interventional radiology?
AB  - Reports in the literature of radiation-induced hair loss are becoming
      increasingly common. This work describes a retrospective dose study of patients
      (n = 958) undergoing diagnostic (primarily cerebral angiograms) and therapeutic
      (primarily cerebral embolisation) procedures in a neuro-interventional suite. A
      comparison of patient doses as dose area product (DAP) readings from a single
      plane image intensifier system (mean DAP value of 8772 cGy cm2) were compared
      with patient doses from a flat panel biplane system (mean DAP value of 7855 cGy
      cm2). Over 80 % of patients requiring neuro-interventional procedures were found
      to undergo two procedures or more. An estimated 7 % of therapeutic procedures
      were found to reach the International Commission on Radiological Protection
      threshold for temporary epilation.

PMID- 21733859
TI  - Breast cancer screening with tomosynthesis--initial experiences.
AB  - Experiences gained so far using tomosynthesis for breast cancer screening will be
      reported. A short summary of results from preparatory studies will also be
      presented. The sensitivity and specificity of breast tomosynthesis (BT) will be
      compared with conventional two-dimensional digital mammography (DM) for breast
      cancer screening in a population-based study. Over 2000 women have been examined
      so far with BT and DM. The BT reading is significantly more time-consuming than
      the DM reading. Preparatory studies have shown that BT has a higher diagnostic
      precision and higher accuracy of size measurements and stage determination than
      DM. There is potential to use lower compression force with BT compared with DM,
      without decreasing the diagnostic accuracy. BT might play an important role in
      clinical as well as screening mammography. A large-scale population-based study
      to investigate BT as a screening modality is underway.

PMID- 21733860
TI  - Radiation protection at Hadron therapy facilities.
AB  - The Italian National Centre for Oncological Hadrontherapy is currently under
      construction in Pavia. It is designed for the treatment of deep-seated tumours
      (up to a depth of 27 cm of water equivalent) with proton and C-ion beams as well
      as for both clinical and radiobiological research. The particles will be
      accelerated by a 7-MeV u(-1) LINAC injector and a 400-MeV u(-1) synchrotron. In
      the first phase of the project, three treatment rooms will be in operation,
      equipped with four fixed beams, three horizontal and one vertical. The
      accelerators are currently undergoing commissioning. The main radiation
      protection problems encountered (shielding, activation, etc.) are hereby
      illustrated and discussed in relation to the constraints set by the Italian
      national authorities.

PMID- 21733861
TI  - Effects of high ambient temperature on glow-peak fading properties of LiF:Mg,Ti
      thermoluminescent dosemeters.
AB  - The effects of a controlled high temperature environment on LiF:Mg,Ti
      thermoluminescent dosemeters (TLDs) were investigated. TLDs were exposed to
      ambient temperatures of 30, 40 and 50 degrees C. Sensitivity changes before
      irradiation, typically called pre-irradiation fading, and signal loss after
      irradiation, called post-irradiation fading, were studied. Dosemeters were
      subjected to up to 33 d of pre-irradiation and 68 d of post-irradiation storage.
      For pre-irradiation fading, peak 5 showed a signal increase of ~30 % and peak 4
      showed an ~30 % decrease in 20 d. The sum of the areas of peaks 4 and 5 remained
      relatively constant even for long pre-irradiation times, although at 50 degrees
      C, losses in peak 5 signal were too significant to maintain the sum of peaks 4
      and 5 constant. Peak 3 was still detectable even at 50 degrees C and the longest
      irradiation times, but peak 2 was very difficult to detect after 15-20 d,
      especially with post-irradiation fading.

PMID- 21733862
TI  - A national programme for patient and staff dose monitoring in interventional
      cardiology.
AB  - A national programme on patient and staff dose evaluation in interventional
      cardiology made in cooperation with the haemodynamic section of the Spanish
      Society of Cardiology has recently been launched. Its aim is to propose a set of
      national diagnostic reference levels (DRLs) for patients as recommended by the
      International Commission on Radiological Protection and to initiate several
      optimisation actions to improve radiological protection of both patients and
      staff. Six hospitals have joined the programme and accepted to submit their data
      to a central database. First to be acquired were the quality control data of the
      X-ray systems and radiation doses of patients and professionals. The results from
      9 X-ray systems, 1467 procedures and staff doses from 43 professionals were
      gathered. Provisional DRLs resulted in 44 Gy cm(2) for coronary angiography and
      78 Gy cm(2) for interventions. The X-ray systems varied up to a factor of 5 for
      dose rates in reference conditions. Staff doses showed that 50 % of
      interventional cardiologists do not use their personal dosemeters correctly.

PMID- 21733863
TI  - How 'do's' and 'dont's' can be of significant importance in radiation protection:
      a case report.
AB  - The Norwegian Radiation Protection Authority (NRPA) was contacted by a cardiology
      department because of a suspicious radiation burn on a patient. The patient had
      undergone two bi-ventricular pacemaker implantations and the lesion was
      recognised as radiation dermatitis. The NRPA sent sets of thermoluminescense
      dosemeters to the department to measure the skin dose on eight successive
      patients undergoing bi-ventricular pacemaker implantations. The average maximum
      entrance surface dose for the eight patients was 5.3 Gy, ranging from 2.0 to 13.1
      Gy. A site audit was performed during a procedure, with the aim to observe the
      general skills in radiation protection. Based on the findings in the audit, a few
      very simple 'Do's' and 'Don'ts' were highlighted in a meeting directly after the
      audit. After the audit, dose measurements were performed on six new patients
      showing an average maximum entrance surface dose of 0.4 Gy, ranging from 0.2 to
      0.8 Gy. The aim of this work was to illustrate the dose reductions that are
      possible to achieve with a very few basic advices, especially when the operator
      has suboptimal competence.

PMID- 21733864
TI  - Dosimetry using Gafchromic XR-RV2 radiochromic films in interventional radiology.
AB  - Patient dose measurements of local entrance dose to the skin have been carried
      out using radiochromic film (Gafchromic XR-RV2) in a sample of interventional
      procedures. The major aim of the work was to measure patient entrance dose from
      such examinations using Gafchromic XR-RV2. Forty-five various interventional
      procedures (including nefrostomies and urinary stenting, biliary stenting and
      percutaneous transhepatic biliary drainage (PTBD) and aorta stent grafting) were
      evaluated. Maximum entrance doses were 537 +/- 119 mGy in nephrostomies, 943 +/-
      631 mGy in biliary stenting and PTBD and 2425 +/- 569 mGy in aorta stent
      grafting. Results indicate that all patients undergoing aorta stent grafting
      received skin dose above 1500 mGy, which means that there is an increasing
      potential to suffer radiation-induced skin injuries. The film provides dose
      mapping, the position of the skin area with highest dose and can be used for
      immediate qualitative and as well as for quantitative assessment of patient skin
      dose.

PMID- 21733865
TI  - Increases in patient doses need to be avoided when upgrading interventional
      cardiology systems to flat detectors.
AB  - The aim of this study was to evaluate patient doses in two interventional
      cardiology laboratories over a period of 1 y in which the imaging devices were
      changed from image intensifier (II) to flat detector (FD). Dosimetric data from a
      total of 1040 coronary angiography (CA) procedures and 1087 percutaneous
      transluminal coronary angioplasty (PTCA) procedures were gathered. During the
      period studied with II imaging, median values of dose area product were 28 Gy
      cm(2) for CA and 57 Gy cm(2) for PTCA. In the first half of the year with FD
      imaging, median values were 37 Gy cm(2) for CA and 89 Gy cm(2) for PTCA. A
      significant increase in patient doses was noticed in the early stages of use of
      FD technology for imaging IC procedures, while fluoroscopy time and number of
      images remained similar. A careful setting of the X-ray systems, after upgrading
      the imaging system, is essential to avoid unjustified increases in patient doses.

PMID- 21733866
TI  - Performance of mammography equipment in the Macedonian breast screening campaign
      2008/2009.
AB  - Breast screening campaign in Macedonia started in the end of 2007 and 19 national
      mammography departments were included. Contrary to the European Guidelines for
      Quality Assurance in Mammography Screening, the quality assurance activities were
      not implemented before the start of the campaign, except at the University Clinic
      of Radiology, Skopje. The quality control tests were performed for the very first
      time at 13 mammography units under a licence-obtaining procedure. One of the
      machines was suspended from clinical and screening practice due to heavy
      malfunction of the generator, X-ray tube and automatic exposure control (AEC)
      system. Only 3 of the 13 mammography machines met the criteria for tube voltage
      (kV) accuracy. Two of the seven AEC systems were calibrated in the optimal
      optical density (OD) range (OD >1.4). AEC settings corresponded to the
      recommendations at eight units, while nine units met basic overall image quality
      criteria. Mean glandular dose (MGD) was higher than the recommended level of 2.5
      mGy in four departments. Mean gradient of the film G(0.25-2.0) was below 2.8 at
      four units. Only two light boxes had a luminance of >1700 cd m(-2) and six rooms
      had an ambient light level of <50 lx. The findings of this work clearly suggest
      that the performance of the mammography equipment involved in the campaign in
      almost 50 % do not supply basic quality criteria for a breast screening
      programme.

PMID- 21733867
TI  - A study on occupational exposure in a PET/CT facility.
AB  - Staff occupational exposure for (18)F-FDG studies has been assessed. For this
      purpose, different detectors, all traceable to PTB standards, have been used.
      Measurements were carried out in different working areas in the facility for
      different procedures and 400 MBq per patient standard injected activity. A
      radiological map of the patient lying on the couch was obtained; the largest dose
      rate result was obtained in contact with the patient's abdomen. The maximum dose
      to the most exposed staff member for this position is 3.6 mSv y(-1), under some
      conservative assumptions. A typical value would be 0.9 +/- 0.3 mSv y(-1) close to
      the abdomen, taking into account staff rotations. These results have been
      obtained from a sample of 50 patients and average values have been statistically
      tested. Particularly, a negligible probability of reaching 20 mSv in a year
      (assuming no incidents or contamination) was obtained (P < 0.01). Annual dose
      received by personnel lies well within the recommended limits (International
      Commission on Radiological Protection), these measurements help to optimise
      working procedures in the facility.

PMID- 21733868
TI  - Self-agency in rhesus monkeys.
AB  - Rhesus monkeys (Macaca mulatta) have shown the ability to monitor their own
      mental states, but fail the mirror self-recognition test. In humans, the sense of
      self-agency is closely related to self-awareness, and results from monitoring the
      relationship between intentional, sensorimotor and perceptual information. Humans
      and rhesus monkeys were trained to move a computer icon with a joystick while a
      distractor icon partially matched their movements. Both humans and monkeys were
      able to monitor and identify the icon they were controlling, suggesting they have
      some understanding of self-agency.

PMID- 21733869
TI  - Biodiversity: past, present and future.
AB  - On 12-15 May 2011, a diverse group of students, researchers and practitioners
      from across Canada and around the world met in Banff, Alberta, to discuss the
      many facets of biodiversity science at the 6th Annual Meeting of the Canadian
      Society for Ecology and Evolution.

PMID- 21733870
TI  - Female choice and extra-pair paternity in a traditional human population.
AB  - Seeking out extra-pair paternity (EPP) is a viable reproductive strategy for
      females in many pair-bonded species. Across human societies, women commonly
      engage in extra-marital affairs, suggesting this strategy may also be an
      important part of women's reproductive decision-making. Here, I show that among
      the Himba 17 per cent of all recorded marital births are attributed by women to
      EPP, and EPP is associated with significant increases in women's reproductive
      success. In contrast, there are no cases of EPP among children born into 'love
      match' marriages. This rate of EPP is higher than has been recorded in any other
      small-scale society. These results illustrate the importance of seeking EPP as a
      mechanism of female choice in humans, while simultaneously showing it to be
      highly variable and context-dependent.

PMID- 21733871
TI  - An Early Cambrian stem polychaete with pygidial cirri.
AB  - The oldest annelid fossils are polychaetes from the Cambrian Period. They are
      representatives of the annelid stem group and thus vital in any discussion of how
      we polarize the evolution of the crown group. Here, we describe a fossil
      polychaete from the Early Cambrian Sirius Passet fauna, Pygocirrus butyricampum
      gen. et sp. nov., with structures identified as pygidial cirri, which are
      recorded for the first time from Cambrian annelids. The body is slender and has
      biramous parapodia with chaetae organized in laterally oriented bundles. The
      presence of pygidial cirri is one of the characters that hitherto has defined the
      annelid crown group, which diversified during the Cambrian-Ordovician transition.
      The newly described fossil shows that this character had already developed within
      the total group by the Early Cambrian.

PMID- 21733872
TI  - Long-term cleaner fish presence affects growth of a coral reef fish.
AB  - Cleaning behaviour is considered to be a classical example of mutualism. However,
      no studies, to our knowledge, have measured the benefits to clients in terms of
      growth. In the longest experimental study of its kind, over an 8 year period,
      cleaner fish Labroides dimidiatus were consistently removed from seven patch
      reefs (61-285 m(2)) and left undisturbed on nine control reefs, and the growth
      and parasite load of the damselfish Pomacentrus moluccensis determined. After 8
      years, growth was reduced and parasitic copepod abundance was higher on fish from
      removal reefs compared with controls, but only in larger individuals. Behavioural
      observations revealed that P. moluccensis cleaned by L. dimidiatus were 27 per
      cent larger than nearby conspecifics. The selective cleaning by L. dimidiatus
      probably explains why only larger P. moluccensis individuals benefited from
      cleaning. This is the first demonstration, to our knowledge, that cleaners affect
      the growth rate of client individuals; a greater size for a given age should
      result in increased fecundity at a given time. The effect of the removal of so
      few small fish on the size of another fish species is unprecedented on coral
      reefs.

PMID- 21733873
TI  - A new navigational mechanism mediated by ant ocelli.
AB  - Many animals rely on path integration for navigation and desert ants are the
      champions. On leaving the nest, ants continuously integrate their distance and
      direction of travel so that they always know their current distance and direction
      from the nest and can take a direct path to home. Distance information originates
      from a step-counter and directional information is based on a celestial compass.
      So far, it has been assumed that the directional information obtained from ocelli
      contribute to a single global path integrator, together with directional
      information from the dorsal rim area (DRA) of the compound eyes and distance
      information from the step-counter. Here, we show that ocelli mediate a distinct
      compass from that mediated by the compound eyes. After travelling a two-leg
      outbound route, untreated foragers headed towards the nest direction, showing
      that both legs of the route had been integrated. In contrast, foragers with
      covered compound eyes but uncovered ocelli steered in the direction opposite to
      the last leg of the outbound route. Our findings suggest that, unlike the DRA,
      ocelli cannot by themselves mediate path integration. Instead, ocelli mediate a
      distinct directional system, which buffers the most recent leg of a journey.

PMID- 21733874
TI  - Experimental manipulation of fertility reveals potential lactation costs in a
      free-ranging marsupial.
AB  - Lactation is the most energetically expensive component of reproduction in
      mammals. Theory predicts that reproducing females will adjust their behaviour to
      compensate for increased nutritional demands. However, experimental tests are
      required, since comparisons of the behaviour of naturally reproducing and non
      reproducing females cannot distinguish between true costs of reproduction,
      individual differences or seasonal variation. We experimentally manipulated
      reproduction in free-ranging, eastern grey kangaroos (Macropus giganteus), using
      a fertility control agent. Our novel field experiment revealed that females
      altered their behaviour in direct response to the energetic demands of
      reproduction: reproducing females increased bite rates, and thus food intake,
      when the energetic demands of lactation were highest. Reproducing females did not
      reduce the time spent on vigilance for predators, but increased their forage
      intake on faecal-contaminated pasture, thereby increasing the risk of infection
      by gastrointestinal parasites-a largely unrecognized potential cost of
      reproduction.

PMID- 21733875
TI  - How selection forces dictate the variant surface antigens used by malaria
      parasites.
AB  - Red blood cells infected by the malaria parasite Plasmodium falciparum express
      variant surface antigens (VSAs) that evade host immunity and allow the parasites
      to persist in the human population. There exist many different VSAs and the
      differential expression of these VSAs is associated with the virulence (damage to
      the host) of the parasites. The aim of this study is to unravel the differences
      in the effect key selection forces have on parasites expressing different VSAs
      such that we can better understand how VSAs enable the parasites to adapt to
      changes in their environment (like control measures) and how this may impact the
      virulence of the circulating parasites. To this end, we have built an individual
      based model that captures the main selective forces on malaria parasites, namely
      parasite competition, host immunity, host death and mosquito abundance at both
      the within- and between-host levels. VSAs are defined by the net growth rates
      they infer to the parasites and the model keeps track of the expression of, and
      antibody build-up against, each VSA in all hosts. Our results show an ordered
      acquisition of VSA-specific antibodies with host age, which causes a dichotomy
      between the more virulent VSAs that reach high parasitaemias but are restricted
      to young relatively non-immune hosts, and less virulent VSAs that do not reach
      such high parasitaemias but can infect a wider range of hosts. The outcome of a
      change in the parasite's environment in terms of parasite virulence depends on
      the exact balance between the selection forces, which sets the limiting factor
      for parasite survival. Parasites will evolve towards expressing more virulent
      VSAs when the limiting factor for parasite survival is the within-host parasite
      growth and the parasites are able to minimize this limitation by expressing more
      virulent VSAs.

PMID- 21733876
TI  - Role of shear stress and stretch in vascular mechanobiology.
AB  - Blood vessels are under constant mechanical loading from blood pressure and flow
      which cause internal stresses (endothelial shear stress and circumferential wall
      stress, respectively). The mechanical forces not only cause morphological changes
      of endothelium and blood vessel wall, but also trigger biochemical and biological
      events. There is considerable evidence that physiologic stresses and strains
      (stretch) exert vasoprotective roles via nitric oxide and provide a homeostatic
      oxidative balance. A perturbation of tissue stresses and strains can disturb
      biochemical homeostasis and lead to vascular remodelling and possible dysfunction
      (e.g. altered vasorelaxation, tone, stiffness, etc.). These distinct biological
      endpoints are caused by some common biochemical pathways. The focus of this brief
      review is to point out some possible commonalities in the molecular pathways in
      response to endothelial shear stress and circumferential wall stretch.

PMID- 21733877
TI  - Indicators for assessing folate and vitamin B-12 status and for monitoring the
      efficacy of intervention strategies.
AB  - Deficiencies of folate or of vitamin B-12 are widespread and constitute a major
      global burden of morbidity that affect all age groups. Detecting or confirming
      the presence of folate or vitamin B-12 deficiency and distinguishing one from the
      other depends, ultimately, on laboratory testing. Tests to determine the presence
      of folate or vitamin B-12 deficiency are used singly or in combination to
      establish the nutritional status and prevalence of deficiencies of the vitamins
      in various populations. The efficacy of interventions through the use of
      fortification or supplements is monitored by using the same laboratory tests.
      Tests currently in use have limitations that can be either technical or have a
      biological basis. Consequently, each single test cannot attain perfect
      sensitivity, specificity, or predictive value. Laboratory indicators of vitamin B
      12 or folate status involve the measurement of either the total or a
      physiologically relevant fraction of the vitamin in a compartment such as blood.
      Thus, assays to measure vitamin B-12 or folate in plasma or serum as well as
      folate in red blood cells are in widespread use, and more recently, methods to
      measure vitamin B-12 associated with the plasma binding protein transcobalamin
      (holotranscobalamin) have been developed. Alternatively, concentrations of
      surrogate biochemical markers that reflect the metabolic function of the vitamin
      can be used. Surrogates most commonly used are plasma homocysteine, for detection
      of either vitamin B-12 or folate deficiency, and methylmalonic acid for detection
      of vitamin B-12 deficiency. The general methods as well as their uses,
      indications, and limitations are presented.

PMID- 21733878
TI  - Case studies: iron.
AB  - Iron biomarkers were developed to define the size of iron stores and the adequacy
      of the iron supply required to meet functional needs. Approximately 80% of the
      iron delivered to tissues through the circulating plasma pool will be
      incorporated into hemoglobin. Consequently, with the exception of serum ferritin,
      iron biomarkers are measures of iron sufficiency for erythrocyte production. They
      have proven to be very valuable in the determination of the cause of anemia in
      the clinical setting in which additional information about factors that affect
      the patient's health is available. However, all current biomarkers are affected
      by factors other than iron status, which limit their utility for the
      determination of the prevalence of iron deficiency in some populations,
      particularly in populations who live in developing countries. Furthermore,
      relations between iron status and functional outcomes such as neonatal and infant
      mortality; motor, cognitive, and emotional development in infants; and severe
      morbidity from malaria in young children are inadequately characterized. There is
      a need to identify and standardize biomarkers that have the highest predictive
      value for specific functional outcomes in each setting. The most appropriate
      biomarkers may vary with the setting and be influenced by age, sex, gestational
      stage of pregnancy, and environmental factors such as repeated or chronic
      infections. There is also an urgent need for improved technology to permit the
      use of specific biomarkers in field studies in resource-poor regions. Finally,
      more research is required to define the potential role of hepcidin and non
      transferrin-bound iron assays.

PMID- 21733879
TI  - The prevention of type 2 diabetes: should we recommend vegetable oils instead of
      fatty fish?

PMID- 21733880
TI  - Executive summary--Biomarkers of Nutrition for Development: Building a Consensus.
AB  - The ability to develop evidence-based clinical guidance and effective programs
      and policies to achieve global health promotion and disease prevention goals
      depends on the availability of valid and reliable data. With specific regard to
      the role of food and nutrition in achieving those goals, relevant data are
      developed with the use of biomarkers that reflect nutrient exposure, status, and
      functional effect. A need exists to promote the discovery, development, and use
      of biomarkers across a range of applications. In addition, a process is needed to
      harmonize the global health community's decision making about what biomarkers are
      best suited for a given use under specific conditions and settings. To address
      these needs, the Eunice Kennedy Shriver National Institute of Child Health and
      Human Development, National Institutes of Health, US Department of Health and
      Human Services, organized a conference entitled "Biomarkers of Nutrition for
      Development: Building a Consensus," which was hosted by the International Atomic
      Energy Agency. Partners included key multilateral, US agencies and public and
      private organizations. The assembly endorsed the utility of this initiative and
      the need for the BOND (Biomarkers of Nutrition for Development) project to
      continue. A consensus was reached on the requirement to develop a process to
      inform the community about the relative strengths or weaknesses and specific
      applications of various biomarkers under defined conditions. The articles in this
      supplement summarize the deliberations of the 4 working groups: research,
      clinical, policy, and programmatic. Also described are content presentations on
      the harmonization processes, the evidence base for biomarkers for 5 case-study
      micronutrients, and new frontiers in science and technology.

PMID- 21733881
TI  - Role of vimentin in the inhibitory effects of low-molecular-weight heparin on PC
      3M cell adhesion to, and migration through, endothelium.
AB  - Low-molecular-weight heparin (LMWH) has been used in cancer patients with venous
      thromboembolic complications, resulting in a higher survival rate and an
      inhibitory action on experimental metastasis. In the present study, human
      umbilical vein endothelial cells (HUVECs) were treated with LMWH for 24 h. We
      found that the resulting HUVECs could significantly inhibit the highly metastatic
      human prostate cancer cell line (PC-3M) in terms of its adhesion to the
      endothelium and migration across the endothelium, according to scanning electron
      microscopy. We also determined the elevated levels of endothelial intercellular
      Ca(2+) concentration after the adhesion of PC-3M cells to HUVECs was greatly
      reduced by incubation with LMWH. Using proteomics, we surveyed the global protein
      changes in HUVECs after LMWH treatment and identified four down-regulated
      proteins that were possible isoforms of cytoskeletal vimentin intermediate
      filaments, cartilage-derived C-type lectin, and serine/threonine protein
      phosphatase 1beta (PP-1B). LMWH affected the morphology of vimentin and the
      expression levels of alpha(v) integrin and PP-1B in HUVECs bound to PC-3M cells.
      Vimentin assists in the adhesion of PC-3M cells, which was confirmed by short
      interfering RNA experiments. Furthermore, the direct binding of purified vimentin
      protein with LMWH was detected with surface plasmon resonance methods. However,
      when we used fluorescence-labeled heparin for 24 h to identify whether this
      binding occurred within cells, heparin was distributed principally around
      endothelial cells. Taken together, these findings suggest that the monoincubation
      of LMWH with HUVECs could inhibit PC-3M cell adhesion to, and migration through,
      endothelium. LMWH's regulation of vimentin plays a role in the antimetastatic
      action.

PMID- 21733882
TI  - Bioactivation pathways of the cannabinoid receptor 1 antagonist rimonabant.
AB  - In the present work, the characterization of the biotransformation and
      bioactivation pathways of the cannabinoid receptor 1 antagonist rimonabant
      (Acomplia) is described. Rimonabant was approved in Europe in 2006 for the
      treatment of obesity but was withdrawn in 2008 because of a significant drug
      related risk of serious psychiatric disorders. The aim of the present work is to
      characterize the biotransformation and potential bioactivation pathways of
      rimonabant in vitro in human and rat liver microsomes. The observation of a major
      iminium ion metabolite led us to perform reactive metabolite trapping, covalent
      binding to proteins, and time-dependent inhibition of cytochrome P450 3A4
      studies. The major biotransformation pathways were oxidative dehydrogenation of
      the piperidinyl ring to an iminium ion, hydroxylation of the 3 position of the
      piperidinyl ring, and cleavage of the amide linkage. In coincubations with
      potassium cyanide, three cyanide adducts were detected. A high level of covalent
      binding of rimonabant in human liver microsomes was observed (920 pmol
      equivalents/mg protein). In coincubations with potassium cyanide and
      methoxylamine, the covalent binding was reduced by approximately 40 and 30%,
      respectively, whereas GSH had no significant effect on covalent binding levels.
      Rimonabant was also found to inhibit cytochrome P450 3A4 irreversibly in a time
      dependent manner. In view of these findings, it is noteworthy that, to date, no
      toxicity findings related to the formation of reactive metabolites from
      rimonabant have been reported.

PMID- 21733883
TI  - Thioacetamide intoxication triggers transcriptional up-regulation but enzyme
      inactivation of UDP-glucuronosyltransferases.
AB  - Thioacetamide (TAA) is a potent hepatotoxicant and has been widely used to
      develop experimental liver fibrosis/cirrhosis models. Although the liver toxicity
      of TAA has been extensively studied, little is known about its potential
      influence on UDP-glucuronosyltransferases (UGTs) associated with the development
      of liver fibrosis. The study presented here aimed to uncover the regulation
      patterns of UGTs in TAA-induced liver fibrosis of rats. Potential counteracting
      effects of hepatoprotective agents were also determined. TAA treatment for 8
      weeks induced a significant transcriptional up-regulation of the major UGT
      isoforms, including UGT1A1, UGT1A6, and UGT2B1, accompanied with the dramatic
      elevations of most typical serum biomarkers of liver function and fibrosis
      scores. Upon TAA intoxication, the mRNA and protein levels of the major UGT
      isoforms were increased to 1.5- to 2.5-fold and 2.5- to 3.3-fold of that of the
      normal control, respectively. The hepatoprotective agents Schisandra spp. lignans
      extract and dimethyl diphenyl bicarboxylate could largely abolish TAA-induced up
      regulation of all three UGT isoforms. However, enzyme activities of UGTs remained
      unchanged after TAA treatment. The dissociation of protein expression and enzyme
      activity could possibly be attributed to the inactivating effects of TAA, upon a
      NADPH-dependent bioactivation, on UGTs. This study suggests that the
      transcriptional up-regulation of UGTs may be an alternative mechanism of their
      preserved activities in liver fibrosis/cirrhosis.

PMID- 21733884
TI  - The enigmatic genome of Chara australis virus.
AB  - Most of the genomic sequence of Chara australis virus (CAV), previously called
      Chara corallina virus, has been determined. It is a ssRNA molecule of 9065 nt
      with at least four ORFs. At its 5' end is an ORF encoding a protein of 227 kDa,
      distantly homologous to the multifunctional replicases of benyviruses and
      rubiviruses. Next is an ORF encoding a protein of 44 kDa, homologous to the
      helicases of pestiviruses. The third ORF encodes an unmatched protein of 38 kDa
      that is probably a movement protein. The fourth and 3'-terminal ORF encodes a
      protein of 17.7 kDa homologous to the coat proteins of tobamoviruses. The short
      methyltransferase region of the CAV replicase matches only the C-terminal motif
      of benyvirus methyltransferases. This and other clues indicate that approximately
      11% and 2% of the 5' and 3' termini of the complete CAV genome, respectively, are
      missing from the sequence. The aligned amino acid sequences of the CAV proteins
      and their nearest homologues contain many gaps but relationships inferred from
      them were little affected by removal of these gaps. Sequence comparisons show
      that three of the CAV genes may have diverged from the most closely related genes
      of other viruses 250-450 million years ago, and the sister relationship between
      the genes of CAV and those of benyviruses and tobamoviruses, mirroring the
      ancient sister relationship between charophytes (i.e. the algal host of CAV) and
      embryophytes (i.e. the plant hosts of tobamoviruses and benyviruses), is
      congruent with this possibility.

PMID- 21733885
TI  - Cryptic AUG is important for 48S ribosomal assembly during internal initiation of
      translation of coxsackievirus B3 RNA.
AB  - We have investigated the possible role of a conserved cis-acting element, the
      cryptic AUG, present in the 5' UTR of coxsackievirus B3 (CVB3 ) RNA. CVB3 5' UTR
      contains multiple AUG codons upstream of the initiator AUG, which are not used
      for the initiation of translation. The 48S ribosomal assembly takes place
      upstream of the cryptic AUG. We show here that mutation in the cryptic AUG
      results in reduced efficiency of translation mediated by the CVB3 IRES; mutation
      also reduces the interaction of mutant IRES with a well characterized IRES trans
      acting factor, the human La protein. Furthermore, partial silencing of the La
      gene showed a decrease in IRES activity in the case of both the wild-type and
      mutant. We have demonstrated here that the interaction of the 48S ribosomal
      complex with mutant RNA was weaker compared with wild-type RNA by ribosome
      assembly analysis. We have also investigated by chemical and enzymic
      modifications the possible alteration in secondary structure in the mutant RNA.
      Results suggest that the secondary structure of mutant RNA was only marginally
      altered. Additionally, we have demonstrated by generating compensatory and non
      specific mutations the specific function of the cryptic AUG in internal
      initiation. Results suggest that the effect of the cryptic AUG is specific and
      translation could not be rescued. However, a possibility of tertiary interaction
      of the cryptic AUG with other cis-acting elements cannot be ruled out. Taken
      together, it appears that the integrity of the cryptic AUG is important for
      efficient translation initiation by the CVB3 IRES RNA.

PMID- 21733886
TI  - Determinants of attenuation in the envelope protein of the flavivirus Alfuy.
AB  - Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus endemic to
      Australia and Papua New Guinea. Most strains of MVEV cause potentially fatal
      cases of encephalitis in humans and horses, and have been shown to be highly
      neuroinvasive in weanling mice. In contrast, the naturally occurring subtype
      Alfuy virus (ALFV) has never been associated with human disease, nor is it
      neuroinvasive in weanling mice, even at high doses. To identify viral factors
      associated with ALFV attenuation, a chimeric infectious clone was constructed
      containing the structural genes premembrane (prM) and envelope (E) of ALFV
      swapped into the MVEV genome. The resulting virus (vMVEV/ALFVstr) was no longer
      neuroinvasive in mice, suggesting that motifs within prM-E of ALFV confer
      attenuation. To define these motifs further, mutants were constructed by
      targeting divergent sequences between the MVEV and ALFV E proteins that are known
      markers of virulence in other encephalitic flaviviruses. MVEV mutants containing
      a unique ALFV sequence in the flexible hinge region (residues 273-277) or lacking
      the conserved glycosylation site at position 154 were significantly less
      neuroinvasive in mice than wild-type MVEV, as determined by delayed time to death
      or increased LD(50). Conversely, when the corresponding MVEV sequences were
      inserted into the vMVEV/ALFVstr chimera, the mutant containing the MVEV hinge
      sequence was more neuroinvasive than the parental chimera, though not to the same
      level as wild-type MVEV. These results identify the hinge region and E protein
      glycosylation as motifs that contribute to the attenuation of ALFV.

PMID- 21733887
TI  - The neural basis of deictic shifting in linguistic perspective-taking in high
      functioning autism.
AB  - Personal pronouns, such as 'I' and 'you', require a speaker/listener to
      continuously re-map their reciprocal relation to their referent, depending on who
      is saying the pronoun. This process, called 'deictic shifting', may underlie the
      incorrect production of these pronouns, or 'pronoun reversals', such as referring
      to oneself with the pronoun 'you', which has been reported in children with
      autism. The underlying neural basis of deictic shifting, however, is not
      understood, nor has the processing of pronouns been studied in adults with
      autism. The present study compared the brain activation pattern and functional
      connectivity (synchronization of activation across brain areas) of adults with
      high-functioning autism and control participants using functional magnetic
      resonance imaging in a linguistic perspective-taking task that required deictic
      shifting. The results revealed significantly diminished frontal (right anterior
      insula) to posterior (precuneus) functional connectivity during deictic shifting
      in the autism group, as well as reliably slower and less accurate behavioural
      responses. A comparison of two types of deictic shifting revealed that the
      functional connectivity between the right anterior insula and precuneus was lower
      in autism while answering a question that contained the pronoun 'you', querying
      something about the participant's view, but not when answering a query about
      someone else's view. In addition to the functional connectivity between the right
      anterior insula and precuneus being lower in autism, activation in each region
      was atypical, suggesting over reliance on individual regions as a potential
      compensation for the lower level of collaborative interregional processing. These
      findings indicate that deictic shifting constitutes a challenge for adults with
      high-functioning autism, particularly when reference to one's self is involved,
      and that the functional collaboration of two critical nodes, right anterior
      insula and precuneus, may play a critical role for deictic shifting by supporting
      an attention shift between oneself and others.

PMID- 21733889
TI  - Which components of heart failure programmes are effective? A systematic review
      and meta-analysis of the outcomes of structured telephone support or
      telemonitoring as the primary component of chronic heart failure management in
      8323 patients: Abridged Cochrane Review.
AB  - AIMS: Telemonitoring (TM) and structured telephone support (STS) have the
      potential to deliver specialized management to more patients with chronic heart
      failure (CHF), but their efficacy is still to be proven. The aim of this meta
      analysis was to review randomized controlled trials (RCTs) of TM or STS for all
      cause mortality and all-cause and CHF-related hospitalizations in patients with
      CHF, as a non-invasive remote model of a specialized disease-management
      intervention. METHODS AND RESULTS: We searched all relevant electronic databases
      and search engines, hand-searched bibliographies of relevant studies, systematic
      reviews, and meeting abstracts. Two reviewers independently extracted all data.
      Randomized controlled trials comparing TM or STS to usual care in patients with
      CHF were included. Studies that included intensified management with additional
      home or clinic-visits were excluded. Primary outcomes (mortality and
      hospitalizations) were analysed; secondary outcomes (cost, length of stay, and
      quality of life) were tabulated. Thirty RCTs of STS and TM were identified (25
      peer-reviewed publications (n= 8323) and five abstracts (n= 1482)). Of the 25
      peer-reviewed studies, 11 evaluated TM (2710 participants), 16 evaluated STS
      (5613 participants) with two testing both STS and TM in separate intervention
      arms compared with usual care. Telemonitoring reduced all-cause mortality {risk
      ratio (RR) 0.66 [95% confidence interval (CI) 0.54-0.81], P< 0.0001 }and STS
      showed a similar, but non-significant trend [RR 0.88 (95% CI 0.76-1.01), P=
      0.08]. Both TM [RR 0.79 (95% CI 0.67-0.94), P= 0.008], and STS [RR 0.77 (95% CI
      0.68-0.87), P< 0.0001] reduced CHF-related hospitalizations. Both interventions
      improved quality of life, reduced costs, and were acceptable to patients.
      Improvements in prescribing, patient-knowledge and self-care, and functional
      class were observed. CONCLUSION: Telemonitoring and STS both appear effective
      interventions to improve outcomes in patients with CHF. Systematic Review Number:
      Cochrane Database of Systematic Reviews. 2008:Issue 3. Art. No.: CD007228. DOI:
      10.1002/14651858.CD007228.

PMID- 21733890
TI  - Multiple sclerosis relapses are not associated with exercise.
AB  - Since multiple sclerosis (MS) often affects physically active young individuals,
      it is important to know if exercise can result in increased disease activity.
      Therefore we used a self-report questionnaire to examine the relationship of
      different levels of sports activity and relapses in 632 patients with MS. In
      order to analyse whether subjective recall might have biased the results, we
      performed, in a subgroup of our sample, an objective assessment of clinical data
      and physical fitness parameters. We were unable to find any association between
      sports activity and clinical relapses in either of the two analyses. The group
      with highest activity even shows the lowermost mean values, standard deviations
      and range concerning the number of relapses. Our data suggest that physical
      activity has no significant influence on clinical disease activity.

PMID- 21733891
TI  - Wide inter-individual variability of bispectral index and spectral entropy at
      loss of consciousness during increasing concentrations of dexmedetomidine,
      propofol, and sevoflurane.
AB  - BACKGROUND: The bispectral index (BIS) and the spectral entropy (state entropy,
      SE, and response entropy, RE) are depth-of-anaesthesia monitors derived from EEG
      and have been developed to measure the effects of anaesthetics on the cerebral
      cortex. We studied whether they can differentiate consciousness from
      unconsciousness during increasing doses of three different anaesthetic agents.
      METHODS: Thirty healthy male volunteers aged 19-30 yr were recruited and divided
      into three 10-volunteer groups to receive either dexmedetomidine, propofol, or
      sevoflurane in escalating concentrations at 10 min intervals until loss of
      consciousness (LOC) was reached. Consciousness was tested at 5 min intervals and
      after drug discontinuation at 1 min intervals by requesting the subjects to open
      their eyes. LOC was defined as unresponsiveness to the request and pre-LOC as the
      last meaningful response. The first meaningful response to the request after drug
      discontinuation was defined as regaining of consciousness (ROC). For the
      statistical analysis, pre-LOC and ROC values were pooled to represent the
      responsive state while LOC values represented the unresponsive state. Prediction
      probability (P(K)) was estimated with the jack-knife method. RESULTS: The lowest
      mean values for BIS, SE, and RE were recorded at LOC with all three drugs. The
      P(K) values were low for dexmedetomidine (BIS 0.62, SE 0.58, RE 0.59), propofol
      (BIS 0.73, SE 0.72, RE 0.72), and sevoflurane (BIS 0.70, SE 0.52, RE 0.62).
      CONCLUSIONS: Because of wide inter-individual variability, BIS and entropy were
      not able to reliably differentiate consciousness from unconsciousness during and
      after stepwise increasing concentrations of dexmedetomidine, propofol, and
      sevoflurane.

PMID- 21733892
TI  - Subordinate male cichlids retain reproductive competence during social
      suppression.
AB  - Subordinate males, which are excluded from reproduction often save energy by
      reducing their investment in sperm production. However, if their position in a
      dominance hierarchy changes suddenly they should also rapidly attain
      fertilization capability. Here, we asked how social suppression and ascension to
      dominance influences sperm quality, spermatogenesis and reproductive competence
      in the cichlid Astatotilapia burtoni, where reproduction is tightly coupled to
      social status. Dominant territorial (T) males are reproductively active while
      subordinate non-territorial (NT) males are suppressed, but given the opportunity,
      NT males will perform dominance behaviours within minutes and attain T male
      testes size within days. Using the thymidine analogue 5-bromo-2-deoxyuridine
      (BrdU) to label germ cell proliferation, we found that the spermatogenic cycle
      takes approximately 11-12 days, and social status had no effect on proliferation,
      suggesting that spermatogenesis continues during reproductive suppression.
      Although sperm velocity did not differ among social states, NT males had reduced
      sperm motility. Remarkably, males ascending in status showed sperm motility
      equivalent to T males within 24 h. Males also successfully reproduced within
      hours of social opportunity, despite four to five weeks of suppression and
      reduced testis size. Our data suggest that NT males maintain reproductive
      potential during suppression possibly as a strategy to rapidly improve
      reproductive fitness upon social opportunity.

PMID- 21733893
TI  - Evolution of ruminant headgear: a review.
AB  - The horns, ossicones and antlers of ruminants are familiar and diverse examples
      of cranial appendages. We collectively term ruminant cranial appendages
      'headgear'; this includes four extant forms: antlers (in cervids), horns (in
      bovids), pronghorns (in pronghorn antelope) and ossicones (in giraffids).
      Headgear evolution remains an open and intriguing question because phylogenies
      (molecular and morphological), adult headgear structure and headgear development
      (where data are available) all suggest different pictures of ruminant evolution.
      We discuss what is known about the evolution of headgear, including the evidence
      motivating previous hypotheses of single versus multiple origins, and the
      implications of recent phylogenetic revisions for these hypotheses. Inclusion of
      developmental data is critical for progress on the question of headgear
      evolution, and we synthesize the scattered literature on this front. The areas
      most in need of attention are early development in general; pronghorn and
      ossicone development in particular; and histological study of fossil forms of
      headgear. An integrative study of headgear development and evolution may have
      ramifications beyond the fields of systematics and evolution. Researchers in
      organismal biology, as well as those in biomedical fields investigating skin,
      bone and regenerative medicine, may all benefit from insights produced by this
      line of research.

PMID- 21733894
TI  - Host behaviour and physiology underpin individual variation in avian influenza
      virus infection in migratory Bewick's swans.
AB  - Individual variation in infection modulates both the dynamics of pathogens and
      their impact on host populations. It is therefore crucial to identify
      differential patterns of infection and understand the mechanisms responsible. Yet
      our understanding of infection heterogeneity in wildlife is limited, even for
      important zoonotic host-pathogen systems, owing to the intractability of host
      status prior to infection. Using novel applications of stable isotope ecology and
      eco-immunology, we distinguish antecedent behavioural and physiological traits
      associated with avian influenza virus (AIV) infection in free-living Bewick's
      swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher
      serum delta13C (-25.3+/-0.4) than their non-infected counterparts (-26.3+/-0.2).
      Thus, individuals preferentially foraging in aquatic rather than terrestrial
      habitats experienced a higher risk of infection, suggesting that the abiotic
      requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles
      were more likely to be infected (30.8% compared with 11.3% for adults), shed
      approximately 15-fold higher quantity of virus and exhibited a lower specific
      immune response than adults. Together, these results demonstrate the potential
      for heterogeneity in infection to have a profound influence on the dynamics of
      pathogens, with concomitant impacts on host habitat selection and fitness.

PMID- 21733895
TI  - Common mechanism underlies repeated evolution of extreme pollution tolerance.
AB  - Human alterations to the environment can exert strong evolutionary pressures, yet
      contemporary adaptation to human-mediated stressors is rarely documented in
      wildlife populations. A common-garden experimental design was coupled with
      comparative transcriptomics to discover evolved mechanisms enabling three
      populations of killifish resident in urban estuaries to survive normally lethal
      pollution exposure during development, and to test whether mechanisms are unique
      or common across populations. We show that killifish populations from these
      polluted sites have independently converged on a common adaptive mechanism,
      despite variation in contaminant profiles among sites. These populations are
      united by a similarly profound desensitization of aryl-hydrocarbon receptor
      mediated transcriptional activation, which is associated with extreme tolerance
      to the lethal effects of toxic dioxin-like pollutants. The rapid, repeated,
      heritable and convergent nature of evolved tolerance suggests that ancestral
      killifish populations harboured genotypes that enabled adaptation to twentieth
      century industrial pollutants.

PMID- 21733896
TI  - Blood flow to long bones indicates activity metabolism in mammals, reptiles and
      dinosaurs.
AB  - The cross-sectional area of a nutrient foramen of a long bone is related to blood
      flow requirements of the internal bone cells that are essential for dynamic bone
      remodelling. Foramen area increases with body size in parallel among living
      mammals and non-varanid reptiles, but is significantly larger in mammals. An
      index of blood flow rate through the foramina is about 10 times higher in mammals
      than in reptiles, and even higher if differences in blood pressure are
      considered. The scaling of foramen size correlates well with maximum whole-body
      metabolic rate during exercise in mammals and reptiles, but less well with
      resting metabolic rate. This relates to the role of blood flow associated with
      bone remodelling during and following activity. Mammals and varanid lizards have
      much higher aerobic metabolic rates and exercise-induced bone remodelling than
      non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic
      groups are generally larger than from mammals, indicating a routinely highly
      active and aerobic lifestyle. The simple measurement holds possibilities offers
      the possibility of assessing other groups of extinct and living vertebrates in
      relation to body size, behaviour and habitat.

PMID- 21733897
TI  - Bad to the bone: facial structure predicts unethical behaviour.
AB  - Researchers spanning many scientific domains, including primatology, evolutionary
      biology and psychology, have sought to establish an evolutionary basis for
      morality. While researchers have identified social and cognitive adaptations that
      support ethical behaviour, a consensus has emerged that genetically determined
      physical traits are not reliable signals of unethical intentions or actions.
      Challenging this view, we show that genetically determined physical traits can
      serve as reliable predictors of unethical behaviour if they are also associated
      with positive signals in intersex and intrasex selection. Specifically, we
      identify a key physical attribute, the facial width-to-height ratio, which
      predicts unethical behaviour in men. Across two studies, we demonstrate that men
      with wider faces (relative to facial height) are more likely to explicitly
      deceive their counterparts in a negotiation, and are more willing to cheat in
      order to increase their financial gain. Importantly, we provide evidence that the
      link between facial metrics and unethical behaviour is mediated by a
      psychological sense of power. Our results demonstrate that static physical
      attributes can indeed serve as reliable cues of immoral action, and provide
      additional support for the view that evolutionary forces shape ethical judgement
      and behaviour.

PMID- 21733898
TI  - Male attractiveness regulates daughter fecundity non-genetically via maternal
      investment.
AB  - Mothers can non-genetically influence offspring phenotype in response to
      environmental conditions, including mate attractiveness. If such 'maternal
      effects' influence the offspring's reproduction and F2 generation, there is a
      mechanism for non-genetic trans-generational effects on phenotype, including
      epigenetic phenomena, with implications for evolution and population dynamics. We
      demonstrate in the zebra finch Taeniopygia guttata such non-genetic effects on
      offspring fecundity and the size of early stage F2 (eggs) in response to
      experimentally manipulated father's attractiveness. Our experimental design
      allowed us to deduce that the mechanism for this non-genetic paternal effect was
      via maternal investment in eggs. This affected female offspring size and,
      consequently, fecundity and F2 (egg) size. This demonstrates that female
      perception of mate attractiveness can have non-genetic, trans-generational
      fitness consequences and this may have important implications for the evolution
      of sexually selected traits and population dynamics.

PMID- 21733899
TI  - Unravelling transmission trees of infectious diseases by combining genetic and
      epidemiological data.
AB  - Knowledge on the transmission tree of an epidemic can provide valuable insights
      into disease dynamics. The transmission tree can be reconstructed by analysing
      either detailed epidemiological data (e.g. contact tracing) or, if sufficient
      genetic diversity accumulates over the course of the epidemic, genetic data of
      the pathogen. We present a likelihood-based framework to integrate these two data
      types, estimating probabilities of infection by taking weighted averages over the
      set of possible transmission trees. We test the approach by applying it to
      temporal, geographical and genetic data on the 241 poultry farms infected in an
      epidemic of avian influenza A (H7N7) in The Netherlands in 2003. We show that the
      combined approach estimates the transmission tree with higher correctness and
      resolution than analyses based on genetic or epidemiological data alone.
      Furthermore, the estimated tree reveals the relative infectiousness of farms of
      different types and sizes.

PMID- 21733900
TI  - Changes in species diversity and size composition in the Firth of Clyde demersal
      fish community (1927-2009).
AB  - Following the repeal in 1962 of a long-standing ban on trawling, yields of
      demersal fish from the Firth of Clyde, southwest Scotland, increased to a maximum
      in 1973 and then declined until the directed fishery effectively ceased in the
      early 2000s. Since then, the only landings of demersal fish from the Firth have
      been by-catch in the Norway lobster fishery. We analysed changes in biomass
      density, species diversity and length structure of the demersal fish community
      between 1927 and 2009 from scientific trawl surveys, and related these to the
      fishery harvesting rate. As yields collapsed, the community transformed from a
      state in which biomass was distributed across numerous species (high species
      evenness) and large maximum length taxa were common, to one in which 90 per cent
      of the biomass was vested in one species (whiting), and both large individuals
      and large maximum length species were rare. Species evenness recovered quickly
      once the directed fishery ceased, but 10 years later, the community was still
      deficient in large individuals. The changes partly reflected events at a larger
      regional scale but were more extreme. The lag in response with respect to fishing
      has implications for attempts at managing a restoration of the ecosystem.

PMID- 21733901
TI  - Evidence for instantaneous e-vector detection in the honeybee using an
      associative learning paradigm.
AB  - Many insects use the polarization pattern of the sky for obtaining compass
      information during orientation or navigation. E-vector information is collected
      by a specialized area in the dorsal-most part of the compound eye, the dorsal rim
      area (DRA). We tested honeybees' capability of learning certain e-vector
      orientations by using a classical conditioning paradigm with the proboscis
      extension reflex. When one e-vector orientation (CS+) was associated with sugar
      water, while another orientation (CS-) was not rewarded, the honeybees could
      discriminate CS+ from CS-. Bees whose DRA was inactivated by painting did not
      learn CS+. When ultraviolet (UV) polarized light (350 nm) was used for CS, the
      bees discriminated CS+ from CS-, but no discrimination was observed in blue (442
      nm) or green light (546 nm). Our data indicate that honeybees can learn and
      discriminate between different e-vector orientations, sensed by the UV receptors
      of the DRA, suggesting that bees can determine their flight direction from
      polarized UV skylight during foraging. Fixing the bees' heads during the
      experiments did not prevent learning, indicating that they use an 'instantaneous'
      algorithm of e-vector detection; that is, the bees do not need to actively scan
      the sky with their DRAs ('sequential' method) to determine e-vector orientation.

PMID- 21733902
TI  - Quantitative disease resistance: to better understand parasite-mediated selection
      on major histocompatibility complex.
AB  - We outline a descriptive framework of how candidate alleles of the immune system
      associate with infectious diseases in natural populations of animals. Three kinds
      of alleles can be separated when both prevalence of infection and infection
      intensity are measured--qualitative disease resistance, quantitative disease
      resistance and susceptibility alleles. Our descriptive framework demonstrates why
      alleles for quantitative resistance and susceptibility cannot be separated based
      on prevalence data alone, but are distinguishable on infection intensity. We then
      present a case study to evaluate a previous finding of a positive association
      between prevalence of a severe avian malaria infection (GRW2, Plasmodium
      ashfordi) and a major histocompatibility complex (MHC) class I allele (B4b) in
      great reed warblers Acrocephalus arundinaceus. Using the same dataset, we find
      that individuals with allele B4b have lower GRW2 infection intensities than
      individuals without this allele. Therefore, allele B4b provides quantitative
      resistance rather than increasing susceptibility to infection. This implies that
      birds carrying B4b can mount an immune response that suppresses the acute-phase
      GRW2 infection, while birds without this allele cannot and may die. We argue that
      it is important to determine whether MHC alleles related to infections are
      advantageous (quantitative and qualitative resistance) or disadvantageous
      (susceptibility) to obtain a more complete picture of pathogen-mediated balancing
      selection.

PMID- 21733903
TI  - First record of preserved soft parts in a Palaeozoic podocopid (Metacopina)
      ostracod, Cytherellina submagna: phylogenetic implications.
AB  - The metacopines represent one of the oldest and most important extinct groups of
      ostracods, with a fossil record from the Mid-Ordovician to the Early Jurassic.
      Herein, we report the discovery of a representative of the group with three
      dimensionally preserved soft parts. The specimen--a male of Cytherellina submagna
      -was found in the Early Devonian (416 Ma) of Podolia, Ukraine. A branchial plate
      (Bp) of the cephalic maxillula (Mx), a pair of thoracic appendages (walking
      legs), a presumed furca (Fu) and a copulatory organ are preserved. The material
      also includes phosphatized steinkerns with exceptionally preserved marginal pore
      canals and muscle scars. The morphology of the preserved limbs and valves of C.
      submagna suggests its relationship with extant Podocopida, particularly with the
      superfamilies Darwinuloidea and Sigillioidea, which have many similar
      characteristic features, including a large Bp on the Mx, the morphology of
      walking legs, Fu with two terminal claws, internal stop-teeth in the left valve,
      adductor muscle scar pattern, and a very narrow fused zone along the anterior and
      posterior margins. More precise determination of affinities will depend on the
      soft-part morphology of the cephalic segment, which has not been revealed in the
      present material.

PMID- 21733904
TI  - Neural network detected in a presumed vestigial trait: ultrastructure of the
      salmonid adipose fin.
AB  - A wide variety of rudimentary and apparently non-functional traits have persisted
      over extended evolutionary time. Recent evidence has shown that some of these
      traits may be maintained as a result of developmental constraints or neutral
      energetic cost, but for others their true function was not recognized. The
      adipose fin is small, fleshy, non-rayed and located between the dorsal and caudal
      fins on eight orders of basal teleosts and has traditionally been regarded as
      vestigial without clear function. We describe here the ultrastructure of the
      adipose fin and for the first time, to our knowledge, present evidence of
      extensive nervous tissue, as well as an unusual subdermal complex of
      interconnected astrocyte-like cells equipped with primary cilia. The fin contains
      neither adipose tissue nor fin rays. Many fusiform actinotrichia, comprising
      dense striated macrofibrils, support the free edge and connect with collagen
      cables that link the two sides. These results are consistent with a recent
      hypothesis that the adipose fin may act as a precaudal flow sensor, where its
      removal can be detrimental to swimming efficiency in turbulent water. Our
      findings provide insight to the broader themes of function versus constraints in
      evolutionary biology and may have significance for fisheries science, as the
      adipose fin is routinely removed from millions of salmonids each year.

PMID- 21733905
TI  - The effect of enteral nutrition supplements on serum voriconazole levels.
AB  - This is the case of a 13-year-old Hispanic boy (34.2 kg, 1.14 m(2)) who had
      achieved stable therapeutic levels on voriconazole who later experienced levels
      reported as 'none detected' after the initiation of tube feeds. This case
      outlines the temporal relationship of the effect of tube feeds on voriconazole
      serum levels. Based on this information, voriconazole suspension should not be
      prescribed to patients also receiving supplemental enteral nutrition. In absence
      of formal animal or human pharmacokinetic studies, it is the recommendation of
      the author to separate this combination and to be very vigilant about checking
      serum voriconazole levels in patients on voriconazole suspension and enteral
      nutrition supplements.

PMID- 21733906
TI  - EGFR inhibitors as first-line therapy in EGFR mutation-positive patients with
      NSCLC.
AB  - PURPOSE: The purpose of this review article is to describe the recent data
      supporting the use of epidermal growth factor receptor (EGFR) receptor tyrosine
      kinase inhibitors (TKIs) in the first-line setting of EGFR mutation-positive non
      small cell lung cancer (NSCLC). SUMMARY: EGFR receptor TKIs were originally
      developed in unselected NSCLC patients and demonstrated modest clinical benefit
      compared to placebo. With the discovery of improved benefits in the approximately
      16% of NSCLC patients with an EGFR mutation, trials in selected populations were
      undertaken, demonstrating comparable efficacy to standard chemotherapy with an
      improved toxicity profile. The most common toxicity is rash, sometimes requiring
      dose adjustment and discontinuation and the most serious toxicity is interstitial
      lung disease, which occurs in about 1% of patients treated with EGFR receptor
      TKIs and is fatal in 30% who develop this toxicity. CONCLUSION: The EGFR receptor
      TKIs are an effective therapy in EGFR-mutated NSCLC and are recommended as first
      line therapy for those with advanced or metastatic disease.

PMID- 21733908
TI  - Human scotopic dark adaptation: Comparison of recoveries of psychophysical
      threshold and ERG b-wave sensitivity.
AB  - We have compared the time course of dark adaptation of the human scotopic visual
      system, measured psychophysically and from the b-wave of the electroretinogram
      (ERG), for bleaches ranging from a few percent to near total. We also measured
      light adaptation, in order to apply a "Crawford transformation" to convert the
      raw measurements of dark adaptation into equivalent background intensities. For
      both the "psychophysical threshold equivalent" intensity and the "ERG b-wave
      sensitivity equivalent" intensity, the equivalent background declined over much
      of its range with an "S2" component, though with somewhat different slopes of 
      0.36 (psychophysical) and -0.22 (ERG) log(10) unit min(-1), respectively. In
      addition, the magnitude of the equivalent background was approximately 1 log(10)
      unit lower in the psychophysical experiments than in the ERG experiments. Despite
      these differences, the two approaches extract a common time course for the
      decline in level of free opsin following moderately large bleaches. We conclude
      that the recovery of psychophysical scotopic visual threshold over the S2 region
      reflects events that are present by the stage of the first synapse of rod vision,
      stemming ultimately from the presence of unregenerated opsin in the rod outer
      segments.

PMID- 21733909
TI  - AUXIN-BINDING-PROTEIN1, the second auxin receptor: what is the significance of a
      two-receptor concept in plant signal transduction?
AB  - Since we are living in the 'age of transcription', awareness of aspects other
      than transcription in auxin signal transduction seems to have faded. One purpose
      of this review is to recall these other aspects. The focus will also be on the
      time scales of auxin responses and their potential or known dependence on either
      AUXIN BINDING PROTEIN 1 (ABP1) or on TRANSPORT-INHIBITOR-RESISTANT1 (TIR1) as a
      receptor. Furthermore, both direct and indirect evidence for the function of ABP1
      as a receptor will be reviewed. Finally, the potential functions of a two
      receptor system for auxin and similarities to other two-receptor signalling
      systems in plants will be discussed. It is suggested that such a functional
      arrangement is a property of plants which strengthens tissue autonomy and
      overcomes the lack of nerves or blood circulation which are responsible for rapid
      signal transport in animals.

PMID- 21733910
TI  - Intracardiac blood cyst: rare finding in a complex congenital heart lesion.

PMID- 21733911
TI  - The phosphatonin fibroblast growth factor 23 links calcium-phosphate metabolism
      with left-ventricular dysfunction and atrial fibrillation.
AB  - AIMS: High serum phosphate is linked to cardiovascular morbidity and mortality in
      the general population. Fibroblast growth factor 23 (FGF-23) is a critical
      phosphate regulating hormone, potentially reflecting phosphate load better than a
      single serum phosphate measurement. Recent pioneering echocardiographic studies
      associated FGF-23 with left-ventricular morphology. However, the association
      between FGF-23 and left-ventricular function is unknown, prompting us to
      investigate this relationship in our HOM SWEET HOMe study. METHODS AND RESULTS:
      We studied the association between C-terminal FGF-23, coronary artery disease,
      and left-ventricular function in 885 subjects undergoing elective coronary
      angiography. Left-ventricular function was assessed with ventriculography. More,
      pro-brain natriuretic peptide (pro-BNP) plasma levels were measured. The presence
      of left-ventricular hypertrophy and atrial fibrillation was assessed by
      electrocardiography. Patients with an ejection fraction <40% had significantly
      higher FGF-23 levels compared with patients with the ejection fraction >40% (P<
      0.001). In multivariable regression analysis, the observed relationship between
      FGF-23 and left-ventricular function remained significant after adjustment for
      estimated glomerular filtration rate, presence of left-ventricular hypertrophy,
      and other confounding variables. In accordance, FGF-23 significantly correlated
      with pro-BNP plasma levels (r = 0.31; P< 0.001). Prevalent atrial fibrillation
      was associated with elevated FGF-23 levels, while the presence of coronary artery
      disease was not. CONCLUSIONS: Fibroblast growth factor 23 levels are associated
      with left-ventricular function and atrial fibrillation even in the absence of
      renal function impairment. Of note, these cross-sectional data cannot prove
      causality; therefore, future studies will have to discern whether FGF-23 exerts a
      direct untoward effect on the myocardium, or rather represents an 'innocent
      bystander' which reflects a high phosphate burden.

PMID- 21733912
TI  - Myocardial ischaemia in patients with coronary endothelial dysfunction: insights
      from body surface ECG mapping and implications for invasive evaluation of chronic
      chest pain.
AB  - AIMS: Coronary endothelial dysfunction (ED), by predisposing to abnormal
      vasomotion, may cause chest pain in individuals with non-obstructed coronary
      arteries. The aim of this study was to correlate the magnitude of coronary ED
      with the presence and extent of inducible myocardial ischaemia using body surface
      electrocardiogram (ECG) mapping in symptomatic patients. METHODS AND RESULTS: In
      30 patients with chest pain and angiographically normal coronary arteries or mild
      atherosclerosis, we studied endothelium-dependent responses with acetylcholine
      (ACH) and endothelium-independent function with nitroglycerin and adenosine in
      the left anterior descending artery. Eighty-lead body surface ECG maps were
      collected at baseline and after each dose of ACH. There was a significant
      correlation between the maximal change in epicardial diameter with ACH and the
      magnitude of ST-segment shift [r = -0.44 (95% CI: -0.097 to -0.69), P = 0.015].
      Patients with >= 0.05 mV ST-segment shift/lead had greater epicardial
      vasoconstriction (31.6 vs. 15.6%, P = 0.019), and lower coronary flow reserve
      (2.9 vs. 3.6, P = 0.047) compared with those with ST-segment shift <0.05 mV. Four
      patients had inducible ischaemia with ACH in the absence of abnormal epicardial
      or global microvascular vasomotion (>20% decrease in diameter or <50% increase in
      blood flow). CONCLUSIONS: This study demonstrates that abnormal vasomotion due to
      coronary ED is associated with myocardial ischaemia in patients with chest pain.
      The magnitude of ischaemia correlates with the extent of ED. A small subset of
      patients develop myocardial ischaemia during ACH infusion without significant
      abnormalities in epicardial or global microvascular endothelium-dependent blood
      flow responses.

PMID- 21733913
TI  - Capture of circulatory endothelial progenitor cells and accelerated re
      endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit
      denudation model.
AB  - AIMS: The GenousTM Bio-engineered RTM stent (GS) aims to promote vascular healing
      by capture of circulatory endothelial progenitor cells (EPCs) to the surface of
      the stent struts, resulting in accelerated re-endothelialization. Here, we
      assessed the function of the GS in comparison to bare-metal stent (BMS), when
      exposed to the human and animal circulation. METHODS AND RESULTS: First, 15
      patients undergoing coronary angiography received an extracorporeal femoral
      arteriovenous (AV) shunt containing BMS and GS. Macroscopical mural thrombi were
      observed in BMS, whereas GS remained visibly clean. Confocal and scanning
      electron microscopic (SEM) analysis of GS showed an increase in strut coverage.
      Quantitative polymerase chain reaction (qPCR) analysis of captured cells on the
      GS demonstrated increased expression of endothelial markers KDR/VEGFR2 and E
      selectin, and a decrease in pro-thrombogenic markers tissue factor pathway
      inhibitor and plasminogen activator inhibitor-1 compared with BMS. Secondly, a
      similar primate AV shunt model was used to validate these findings and occlusion
      of BMS was observed, while GS remained patent, as demonstrated by live imaging of
      indium-labelled platelets. Thirdly, in an in vitro cell-capture assay, GS struts
      showed increased coverage by EPCs, whereas monocyte coverage remained similar to
      BMS. Finally, the assessment of re-endothelialization was studied in a rabbit
      denudation model. Twenty animals received BMS and GS in the aorta and iliac
      arteries for 7 days. Scanning electron microscopic analysis showed a trend
      towards increased strut coverage, confirmed by qPCR analysis revealing increased
      levels of endothelial markers (Tie2, CD34, PCD31, and P-selectin) in GS.
      CONCLUSION: In this proof-of-concept study, we have demonstrated that the bio
      engineered EPC-capture stent, GenousTM RTM stent, is effective in EPC capture,
      resulting in accelerated re-endothelialization and reduced thrombogenicity.

PMID- 21733914
TI  - When does a fetus become a person? An Israeli viewpoint.
AB  - BACKGROUND AND METHODOLOGY: 'Biological' and 'human' life or 'personhood' are not
      necessarily identical. While the Catholic Church does not separate the two,
      concluding that human life commences at conception, Judaism endows the fetus with
      personhood gradually throughout the pregnancy. Gradualism is also reflected in
      many Western abortion laws that prohibit 'late abortion'. Importantly, the
      Israeli law does not prohibit abortion at any stage of pregnancy. To examine
      attitudes regarding the status of the fetus vis-a-vis its stages of development,
      a questionnaire presenting ten successive stages was distributed to Israeli
      respondents (n = 281). For each stage participants were asked to grade the fetus
      as having 'personhood' or as a 'living organism' on a five-point scale. Data were
      analysed to show frequency distribution. RESULTS: The fetus gains its ascribed
      personhood gradually. Most of the participants perceived the fetus as a person at
      the stage in which the woman feels its movements. Additionally, many (especially
      secular respondents) evaluated the fetus as a living organism at earlier stages,
      thus making a distinction between the fetus as a living organism and as a person.
      An international comparison with English-speaking countries revealed a local
      'Israeli' tendency to attribute personhood status to the fetus only at a
      relatively late stage. DISCUSSION AND CONCLUSIONS: The 'Israeli' fetus acquires
      its status gradually. This finding challenges the dichotomous conceptualisation
      of the fetus as 'a person' or 'non-person'. The authors conclude by presenting
      the perceived transformation of the fetus to 'personhood' as being influenced by
      national and religious factors.

PMID- 21733915
TI  - Improving nutrition and physical activity in the workplace: a meta-analysis of
      intervention studies.
AB  - A comprehensive search of the literature for studies examining physical activity
      or nutrition interventions in the workplace, published between 1999 and March
      2009, was conducted. This search identified 29 relevant studies. Interventions
      were grouped according to the theoretical framework on which the interventions
      were based (e.g. education, cognitive-behavioural, motivation enhancement, social
      influence, exercise). Weighted Cohen's d effect sizes, percentage overlap
      statistics, confidence intervals and fail safe Ns were calculated. Most
      theoretical approaches were associated with small effects. However, large effects
      were found for some measures of interventions using motivation enhancement.
      Effect sizes were larger for studies focusing on one health behaviour and for
      randomized controlled trials. The workplace is a suitable environment for making
      modest changes in the physical activity, nutrition and health of employees.
      Further research is necessary to determine whether these changes can be
      maintained in the long term.

PMID- 21733916
TI  - Perceptions of gender-based violence among South African youth: implications for
      health promotion interventions.
AB  - Gender-based violence is a widespread problem in South Africa. Past structural
      inequities have created a climate conducive to violence against women. As an
      initial step toward developing a health promotion program, we conducted
      exploratory formative research to examine the barriers that affect the health and
      well-being of youth. Fourteen focus groups (nine with girls and five with boys)
      were conducted with 112 adolescents in a racially mixed community on the
      outskirts of Cape Town, South Africa. We utilized grounded theory and thematic
      analysis to examine the data. The impact of poverty, ubiquitous gendered
      violence, transactional sex and unsafe recreational spaces emerged as the major
      themes. The experiences of youth were consumed by issues of safety rather than
      the pursuit of other developmentally appropriate markers. Our findings suggest
      that health promotion programs should create safe spaces for youth and
      opportunities to critically question the assumptions and manifestations of a
      patriarchal society. Furthermore, the findings indicate that there is a strong
      need for multi-sectorial interventions directed at many levels to prevent gender
      based violence.

PMID- 21733917
TI  - Testing acuity and contrast vision under standardised lighting conditions.
AB  - AIMS: The aim of this work was to construct a lighting device that allows a
      uniform lighting of top illumination charts, as used for the examination of
      contrast vision and visual acuity. The relevant standards make strict demands for
      such charts with regard to the quality of the lighting, the absolute brightness
      and the uniformity of the luminous intensity distribution over the chart surface.
      If measurements are made under differing daylight conditions or if artificial
      light sources are installed in the examination room, as frequently practiced,
      then these requirements cannot be fulfilled. METHODS: A lighting device was
      developed using daylight spectrum tubes installed on the right and left sides of
      the chart. The tubes were shielded by opaque diffusers to scatter the light.
      RESULTS: The device produced an accurate and uniform distribution of luminance at
      21 points over the chart that was not obtained with overhead lighting running
      parallel or horizontal to the chart. CONCLUSION: A uniform illumination of top
      illumination test charts was achieved allowing adherence to the standards for
      measuring acuity set out by the European Union and enabling comparison of such
      visual examinations in multi-centre clinical studies.

PMID- 21733918
TI  - Tachyphylaxis during treatment of exudative age-related macular degeneration with
      ranibizumab.
AB  - AIM: To determine whether tachyphylaxis occurs during treatment with ranibizumab
      (Lucentis, Genentech, Inc., South San Francisco, California, USA) for exudative
      age-related macular degeneration (AMD). DESIGN: Retrospective review of cases.
      PARTICIPANTS: The treatment results of 1076 eyes (976 patients) treated with
      ranibizumab for exudative AMD was evaluated to identify patients with a potential
      tachyphylactic response. The participants had to have a minimum of 12 months
      follow-up. METHODS: Tachyphylaxis was defined as a lack of response to the drug
      at the time of reactivation of choroidal neovascularisation (CNV) in patients who
      had responded to the initial treatment. The authors considered it a lack of
      response to ranibizumab if a decrease in vision and an increase in central
      retinal thickness (CRT) were observed despite repeated injections. Hence a
      stabilisation in vision and/or stabilisation in CRT during treatment were not
      considered tachyphylaxis, and other unfavourable responses such as a tear in the
      retinal pigment epithelium and therefore a decrease in vision during treatment
      were also not considered as tachyphylaxis. Every patient in this cohort who has
      had an injection-free interval after primary inactivation of CNV and who has
      received retreatment at a later stage was identified. In this population, those
      cases that did not respond to retreatment (tachyphylaxis) were identified and
      characterised. MAIN OUTCOME MEASURES: Number of patients who developed
      tachyphylaxis after treatment with ranibizumab. RESULTS: 20 patients (2%)
      developed tachyphylaxis during their treatment. CONCLUSION: Tachyphylaxis can
      occur during the treatment of exudative AMD with ranibizumab. The precise
      mechanism for the development of tachyphylaxis is unclear. Both local and
      systemic factors might be involved.

PMID- 21733919
TI  - Low folate status and indoor pollution are risk factors for endemic optic
      neuropathy in Tanzania.
AB  - AIMS: Bilateral optic neuropathy in Dar-es-Salaam, Tanzania was first reported as
      an epidemic in 1988. Now argued to be endemic in 2010, the aetiology remains
      unclear. The authors investigated the hypothesis that low folate and vitamin B12
      status are associated with optic neuropathy, and also sought to investigate
      whether mercury, commonly used drugs, dietary factors and indoor pollution may
      also be risk factors. METHODS: 57 cases and 102 controls were recruited from two
      tertiary referral centres in Dar-es-Salaam. Data were collected on demographic
      characteristics, diet, medication history and HIV status. Folate and vitamin B12
      (holo-transcobalamin) were measured in stored serum samples. Exposure to mercury
      was assessed from concentrations in random urine samples. RESULTS: Cooking
      indoors more than twice per week (OR 54.48 (95% CI 9.30 to 319.10)) and indoor
      use of charcoal or firewood (OR 21.20 (95% CI 2.51 to 179.36)) increased the risk
      of optic neuropathy. Risk was reduced in those with a higher folate status
      (highest versus lowest quartile OR=0.11 (95% CI 0.02 to 0.51)) and higher protein
      intakes (OR=0.84 (95% CI 0.72 to 0.96). No association was found with mercury
      exposure or any common drug or food commodity. CONCLUSION: This study presents
      the first direct evidence of low folate status and indoor pollution in the
      aetiology of endemic bilateral optic neuropathy in Tanzania.

PMID- 21733920
TI  - Comparison of manually corrected retinal thickness measurements from multiple
      spectral-domain optical coherence tomography instruments.
AB  - BACKGROUND/AIMS: To compare retinal thickness measurements from three different
      spectral domain optical coherence instruments when manual segmentation is
      employed to standardise retinal boundary locations. METHODS: 40 eyes of 21
      healthy subjects were scanned on the Cirrus HD-OCT, Topcon 3D-OCT-2000 and
      Heidelberg Spectralis-OCT. Raw data were imported into custom grading software
      (3D-OCTOR). Manual segmentation was performed on every data set, and retinal
      thickness values in the foveal central subfield were computed. RESULTS: 37 eyes
      of 20 subjects were gradable on every machine. The average retinal thicknesses
      for these eyes were 236.7 MUm (SD 20.1), 235.7 MUm (SD 20.4) and 236.5 MUm (SD
      18.0) for the Cirrus, 3D-OCT-2000 and Spectralis, respectively. Comparing manual
      retinal thickness measurements between any two machines, the maximum difference
      was 18.2 MUm. The mean absolute differences per eye between two machines were:
      4.9 MUm for Cirrus versus 3D-OCT-2000, 3.7 MUm for Cirrus versus Spectralis and
      4.4 MUm for 3D-OCT-2000 versus Spectralis. CONCLUSIONS: When a uniform position
      is used to locate the outer retinal boundary, the retinal thickness measurements
      derived from three different spectral domain optical coherence instruments
      devices are virtually identical. Manual correction may allow OCT-derived
      thickness measurements to be compared between devices in clinical trials and
      clinical research.

PMID- 21733921
TI  - Response to: the utility of relative afferent pupillary defect as a screening
      tool for glaucoma: prospective examination of a large population-based study in a
      south Indian population.

PMID- 21733922
TI  - Early clinical outcomes of implantation of posterior chamber phakic intraocular
      lens with a central hole (Hole ICL) for moderate to high myopia.
AB  - AIM: To assess the early clinical outcomes of an ICL with a central hole (Hole
      ICL) implantation for the correction of moderate to high myopia. METHODS: This
      study evaluated 20 eyes of 20 patients with spherical equivalents of -7.36 +/-
      2.13 D (mean +/- SD) who underwent Hole ICL implantation. Before surgery and at 1
      week and 1, 3 and 6 months after surgery, we assessed the safety, efficacy,
      predictability, stability and adverse events of the surgery. RESULTS: Logarithm
      of the minimum angle of resolution (logMAR) uncorrected visual acuity and logMAR
      best spectacle-corrected visual acuity were -0.20 +/- 0.12 and -0.25 +/- 0.06,
      respectively, 6 months after surgery. The safety and efficacy indices were 1.13
      +/- 0.24 and 1.03 +/- 0.30, respectively. At 6 months, 95%, and 100% eyes were
      within +/- 0.5 and +/- 1.0 D of the targeted correction, respectively. Change in
      manifest refraction from week 1 to month 6 was 0.06 +/- 0.28 D. No significant
      rise in intraocular pressure (including pupillary block) or a secondary cataract
      occurred in any case during the period of observation. CONCLUSIONS: Implantation
      of a newly developed Hole ICL offered good results for all measures of safety,
      efficacy, predictability and stability for the correction of moderate to high
      myopic errors, even without peripheral iridectomy, suggesting its viability as a
      surgical option for the treatment of such eyes.

PMID- 21733923
TI  - Changing trends in keratoplasty in the West of Scotland: a 10-year review.
AB  - BACKGROUND/AIMS: To review the indications and types of keratoplasty performed in
      the West of Scotland between 2001 and 2010. METHODS: A retrospective analysis of
      the histopathological diagnoses of all corneal buttons submitted to the regional
      Ocular Pathology Laboratory (Glasgow, UK) between January 2001 and December 2010
      was performed. RESULTS: Between 2001 and 2010, a total of 921 keratoplasties were
      performed in the West of Scotland. These included 646 (70.1%) penetrating
      keratoplasties and 275 (29.9%) lamellar keratoplasties (LK). Keratoconus (n=264,
      28.7%) was the leading indication for keratoplasty, followed by graft failure
      (n=177, 19.2%), Fuch's endothelial dystrophy (n=124, 13.5%), keratitis (n=106,
      11.5%), pseudophakic/aphakic bullous keratopathy (n=88, 9.6%), endothelial
      failure (n=67, 7.3%), non-Fuch's corneal dystrophies (n=21, 2.3%), trauma (n=19,
      2.0%), autoimmune/inflammatory diseases (n=16, 1.7%) and others (n=39, 4.2%). A
      significant increase in the proportion of LK over penetrating keratoplasty was
      observed during this 10-year period: from 14.1% LK (2001-2005) to 40.4% LK
      (chi(2)=71.78, p value<0.001). CONCLUSION: Keratoconus was the leading indication
      for keratoplasty in the West of Scotland. Both anterior LK and endothelial
      keratoplasty seemed to show an emerging trend as the procedures of choice for
      dealing with anterior and posterior corneal pathologies, respectively.

PMID- 21733924
TI  - Prostate cancer screening has no effect on prostate cancer specific mortality
      over 20 years of follow-up of Swedish men.

PMID- 21733925
TI  - Six-month interventions - parent-centred dietary modification alone or in
      combination with child-centred physical activity may reduce child BMI at 2 years.

PMID- 21733926
TI  - Economic evaluation alongside the Premature Infants in Need of Transfusion
      randomised controlled trial.
AB  - BACKGROUND: The Premature Infants in Need of Transfusion (PINT) Outcome Study
      showed no significant difference in the primary outcome of death or
      neurodevelopmental impairment (NDI) in extremely low birthweight (ELBW) infants.
      However, a post-hoc analysis expanding the definition of NDI to include
      borderline intellectual functioning (Mental Development Index (MDI) <85) found an
      improvement in outcomes in the group maintained at higher haemoglobin levels.
      OBJECTIVE: To determine the cost effectiveness of more frequent red blood cell
      transfusions (high-Hb threshold) compared with less frequent transfusions (low-Hb
      threshold) in ELBW infants. DESIGN/METHODS: The authors performed an economic
      evaluation using patient-level data collected during the PINT randomised trial.
      The authors measured comprehensive costs from a third-party payer's perspective
      over a time horizon from birth through 18-21 months corrected age. RESULTS: The
      average total cost in the high-Hb threshold group was CAN$149 767 compared with
      CAN$150 227 in the low-Hb threshold group (difference of CAN$460, p=0.96). Cost
      effectiveness analysis estimated savings of CAN$6879 for every additional infant
      surviving without severe NDI. There was a 48% chance that the high-Hb threshold
      reduced costs while improving outcome and a 90% chance that it would be cost
      effective at a willingness-to-pay threshold of CAN$250 000 per additional
      survivor without severe NDI. Post-hoc analysis defining cognitive delay as MDI
      score <85, instead of <70, revealed savings in the high-Hb threshold group of
      CAN$4457 per additional survivor without NDI. Results were robust to
      deterministic sensitivity analyses. CONCLUSION: A high-Hb threshold for
      transfusion, as measured in ELBW PINT study infants through 18 months corrected
      gestational age, may be an economically appealing intervention. The estimates
      were associated with moderate statistical uncertainty that should be targeted in
      larger, future studies.

PMID- 21733927
TI  - Pharmacogenetics and pharmacogenomics: a clinical reality.
AB  - Pharmacogenetics and pharmacogenomics strive to explain the interindividual
      variability in response to drugs due to genetic variation. For certain drugs,
      genetic tests can reduce adverse drug reactions and improve treatment efficacy.
      In this review, we will briefly consider some successful tests introduced into
      clinical practice and potential future developments.

PMID- 21733928
TI  - Quality indicators for laboratory diagnostics: consensus is needed.

PMID- 21733929
TI  - Comparison of total and intact aminoterminal propeptide of type I procollagen
      assays in patients with breast cancer with or without bone metastases.
AB  - BACKGROUND: Aminoterminal propeptide of type I procollagen (PINP) reflects bone
      formation. Two different antigens exist in human serum: intact PINP and a
      monomeric form. The intact PINP assay measures trimeric form and the total assay
      measures both forms. The structure and origin of the monomeric form is still
      unclear. METHODS: Automated intact and total PINP assays were compared in breast
      cancer patients with (n = 60) or without bone metastases (n = 226). In addition,
      cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was measured
      from the same patients and compared with the concentration of PINP monomer
      (difference between intact and total PINP). Monomeric PINP was purified from
      human ascitic fluid and characterized by sodium dodecyl sulphate polyacrylamide
      gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: The correlations were
      good (r > 0.948) between intact PINP and total P1NP in all patient groups. The
      correlation between the monomeric form and ICTP was lower in patients without
      bone metastases (r = 0.507) than in patients with bone metastases (r = 0.894).
      This indicates that the monomeric form reflects the degradation of type I
      collagen because bone metastases are osteolytic in nature. After several steps in
      the purification of the monomer form there was a single peak. Only the single
      band was visible in the SDS-PAGE gel. The alpha1-chain of intact PINP consists of
      161 amino acids with a molecular weight of 14224.02. The purified monomer peptide
      in MALDI-TOF MS was smaller, 10576.41, and most likely cleaved after the arginine
      residue (amino acid number 120) with a trypsin-like protease. CONCLUSIONS: Intact
      and total PINP assays give similar results in many conditions, but there are
      differences, for example in breast carcinoma, which should be recognized.

PMID- 21733931
TI  - Pervasive refusal syndrome.
AB  - We report here on a case of severe pervasive refusal syndrome. This is of
      interest for three reasons. Firstly, most reported cases are adolescent girls;
      our case is regarding an adolescent boy. Secondly, he was successfully treated at
      home and thirdly, the serology showed an apparent infective pre-cursor to the
      illness with evidence of possible autoimmune serology. A 14-year old boy
      deteriorated from a picture where diagnosed CFS/ME developed into Pervasive
      Refusal Syndrome. This included the inability to move or speak, with closed eyes,
      multiple tics, facial grimacing, heightened sensitivity to noise (hyperacusis)
      and touch (hyperaesthesia), and inability or unwillingness to eat anything except
      small amounts of sloppy food. Successful rehabilitation is reported. Finally the
      issue of nomenclature is discussed, raising the question whether Pervasive
      Refusal Syndrome would be better renamed in a way that does not imply that the
      condition is always volitional and oppositional, as this can distract focus away
      from an alliance between family and clinicians.

PMID- 21733932
TI  - A qualitative exploration of child clinical psychologists' understanding of user
      involvement.
AB  - 'Service User Involvement' is a key directive for mental health services. This is
      thought to be especially complex in child services-despite evidence that it can
      be achieved-because of the need to use developmentally-appropriate tools.
      Children are in a multi-faceted position of disempowerment when they enter mental
      health services; attempts to involve them in these services are entangled with
      intricate power issues. To explore these issues, eight Clinical Psychologists who
      work with children were interviewed about their views and experiences of User
      Involvement. Their accounts were analysed by drawing on Foucauldian Discourse
      Analysis. The resulting account demonstrates how children are consistently
      positioned as both vulnerable and powerless (in contrast to parents and
      professionals). This has the effect of rendering them as less-than-ideal
      candidates for involvement in service evaluation and planning, in a context where
      parents may seem to offer a more straightforward option to professionals, and
      where those professionals see themselves as having to operate within certain
      constraints.

PMID- 21733933
TI  - Combining individual cognitive behaviour therapy and caregiver-child sessions for
      childhood depression: an open trial.
AB  - The objective was to obtain preliminary evidence on the feasibility and efficacy
      of combining individual cognitive behavior therapy (CBT) with complimentary
      caregiver-child sessions for depressed youths. Fifteen children participated in
      an open clinical trial. Treatment included 16 CBT sessions combined with seven
      caregiver/caregiver-child sessions over 12 weeks. Data were collected at pre-,
      mid-, and post-treatment and at one- and six-month follow-ups. Significant
      decreases in depressive symptoms were apparent, with the majority showing
      clinically meaningful improvement. Benchmarked against the literature, the
      combination equaled or outperformed CBT in other studies and was superior to
      control conditions. Mother and teacher reports of child functioning significantly
      improved, providing social validation of the effects. Mothers reported improved
      caregiver-child relationships and less parenting stress. Children did not report
      acute improvements in relations with their caregivers. However, when a father
      participated, improved father-child relations were reported in the follow-up
      period. Younger age and lower pretreatment severity predicted greater symptom
      change. The positive treatment effects provide support for the combined
      intervention and suggest a further research focus on the effects of caregiver
      involvement in the treatment of depressed youths.

PMID- 21733934
TI  - Compliance with antithrombotic guidelines in surgery patients in German
      hospitals: a multicenter study involving pharmacy interns.
AB  - Despite the existence of antithrombotic guidelines, there is low compliance with
      these guidelines in clinical practice. Until now pharmacy interns (PIs) have not
      been involved in this process. The objectives were to involve PIs to evaluate
      compliance with antithrombotic guidelines for VTE prophylaxis in surgery
      patients, and in cases of noncompliance to carry out pharmaceutical
      interventions. The study was conducted in 7 hospitals in Germany involving 27 PIs
      within the project "Pharmacy interns on the ward" (P-STAT 2). Pharmacy interns
      determined the thromboembolic risk, documented antithrombotic medication, and
      checked the compliance with current antithrombotic guidelines. A total of 6491
      patients were enrolled; 5695 patients received antithrombotic prophylaxis.
      Antithrombotic guideline was followed in 77.5% patients. Many patients are not
      receiving appropriate VTE prophylaxis or heparin bridging regimen despite the
      fact that evidence-based antithrombotic guidelines are available. Pharmacy
      interns may play an important role in antithrombotic management.

PMID- 21733935
TI  - Defibrotide blunts the prothrombotic effect of thalidomide on endothelial cells.
AB  - Patients with multiple myeloma (MM) are at relatively high risk of developing
      thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy
      has been identified to increase this risk. Defibrotide (DF), a polydisperse
      oligonucleotide, showed previously to counteract the alterations in endothelial
      cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the
      impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis
      induced by thalidomide. In this in vitro study, MM by itself alters the
      profibrinolytic potential of ECs decreasing the tissue plasminogen activator (t
      PA) and increasing the plasminogen activator inhibitor 1 (PAI-1) levels which is
      potentiated by thalidomide. Defibrotide was able to counteract these effects.
      Additionally, DF upregulated the t-PA and downregulated PAI-1 gene expression
      modulated by thalidomide. Defibrotide also protects ECs from thalidomide-mediated
      cell death without interfering with its antitumor effects. These findings support
      DF clinical use for the prevention of DVT induced by immunomodulatory drugs.

PMID- 21733936
TI  - The role of Factor V Leiden in adult patients with venous thromboembolism: a meta
      analysis of published studies from Turkey.
AB  - Factor V Leiden (FVL) is the most common inherited risk factor for venous
      thromboembolism (VTE). The frequency of FVL in patients with VTE has been
      reported from different parts of Turkey. A meta-analysis was performed to
      estimate the risk of VTE associated with FVL in Turkish population. Published
      studies were retrieved from Pubmed and Science Citation Index/Expanded. We
      selected studies comparing the prevalence of FVL in patients with VTE with
      controls. The analysis was performed by the software comprehensive meta-analysis.
      The analysis consisted of 10 studies including 1202 patients with VTE and 1283
      controls. The pooled frequency of FVL was significantly higher in patients with
      VTE (22.8%) than controls (7.6%). The pooled odds ratio (OR) was 3.4 (95%
      confidence interval [CI], 2.6-4.5). The study showed homogeneity (Q value,
      9.955). No publication bias was observed in any comparison model. Our meta
      analysis showed an association of FVL with VTE in Turkey.

PMID- 21733937
TI  - Hemostatic treatment using factor VIII concentrates for neutralizing high
      responding inhibitors prior to CVAD insertion for immune-tolerance induction
      therapy.
AB  - We have utilized high-dose factor VIII (FVIII) concentrates in 4 hemophilia A
      patients with inhibitors prior to surgery for the insertion of a central venous
      access device. In total, 3 patients out of 4 had high responding inhibitors.
      Dosing algorithms for this type of therapy have not been previously validated and
      established. We devised an effective formula to calculate the initial dose
      required to neutralize the inhibitors, although some of the patients demonstrated
      a lower recovery of FVIII than expected. An anamnestic inhibitor response was
      evident in 3 cases, but overall our strategy provided a reliable hemostatic
      effect for at least 4 days after surgery. In addition, our protocol appeared to
      be more cost-effective than FVIII bypass therapy. The financial saving in 1 case
      for the initial 3 days was estimated to be approximately US$49 122. Our results
      demonstrated that high-dose FVIII therapy provided clinically effective and
      economically viable results even in high responders.

PMID- 21733938
TI  - Platelet and monocyte activation in acute ischemic stroke--is there a correlation
      with stroke etiology?
AB  - An upregulation of platelet CD40 ligand (CD40L) and CD62P has been described in
      atherosclerotic cardiovascular diseases and among patients with acute cerebral
      ischemia. Correlation between platelet and monocyte activation and the etiology
      of ischemic stroke were examined in 41 patients with acute ischemic stroke.
      Compared to 10 controls, all patients with stroke showed a significantly elevated
      platelet expression of CD40L (P < .001) and had significantly higher amounts of
      platelet-monocyte aggregates (P = .002). Plasma levels of interleukin 7 were
      significantly lower in patients with stroke compared to controls (P = .006).
      Patients with small artery disease had a significantly higher platelet CD40L
      expression than patients with cardioembolic stroke (P = .029). Plasma levels of
      soluble CD40L were significantly higher in patients with large artery disease
      compared to patients with cardioembolic stroke (P = .047). In conclusion,
      patients with acute ischemic stroke show an upregulation of platelet CD40L and an
      activation of cellular coagulation with highest activation in the large artery
      disease subgroup.

PMID- 21733939
TI  - Early coagulopathy in patients with ruptured abdominal aortic aneurysm.
AB  - Ruptured abdominal aortic aneurysm (AAA) is associated with a high mortality
      despite surgical management. Earlier reports indicate that a major cause of
      immediate intraoperative death in patients with ruptured AAA is related to
      hemorrhage due to coagulopathy. Acidosis is, besides hypothermia and
      hemodilution, a possible cause of coagulopathy. The aim of the present study was
      to investigate the incidence of coagulopathy and acidosis preoperatively in
      patients with ruptured AAA in relation to the clinical outcome with special
      regard to the influence of shock. For this purpose, 95 consecutive patients who
      underwent surgery for AAA (43 ruptured with shock, 12 ruptured without shock, and
      40 nonruptured) were included. Coagulopathy was defined as prothrombin time
      (international normalized ratio [INR]) >=1.5 and acidosis was defined as base
      deficit >=6 mmol/L. Mortality and postoperative complications were recorded. The
      present study shows a state of acidosis at the start of surgery in 30 of 55
      patients with ruptured AAA. However, only in 7 of 55 patients with ruptured AAA a
      state of preoperative coagulopathy was demonstrated. Furthermore, in our patients
      with shock due to ruptured AAA only 2 of 12 deaths were due to coagulopathy and
      bleeding. Indeed, our results show a relatively high incidence of thrombosis
      related causes of death in patients with ruptured AAA, indicating a relation to
      an activated coagulation in these patients. These findings indicate that modern
      emergency management of ruptured AAA has improved in the attempt to prevent fatal
      coagulopathy.

PMID- 21733940
TI  - Effects of antiphospholipid antibodies on in vitro platelet aggregation.
AB  - Antiphospholipid antibodies contribute to the development of thrombosis, although
      precise mechanisms remain to be elucidated. We determined the effects of affinity
      purified anti-beta(2)-glycoprotein 1 (anti-beta(2)GP1) and anti-prothrombin (anti
      PT) antibodies on in vitro platelet aggregation. Adenosine diphosphate (ADP) and
      collagen-induced platelet aggregation were performed using platelet-rich plasma
      ([PRP] 250 * 10(9)/L). Antiphospholipid antibodies (1.25-10 MUg/mL) were
      preincubated with PRP for 10 minutes at 37 degrees C prior to the addition of
      agonist. Anti-beta(2)GP1 antibodies significantly reduced platelet aggregation
      (percentage area under the curve; %AUC) in a concentration-dependent manner using
      both 5 MUmol/L (P < .001) and 2.5 MUmol/L (P = .038) ADP but did not
      significantly affect the rate of aggregation. Anti-PT antibodies significantly
      enhanced 5 ug/mL collagen-induced platelet aggregation (%AUC; P = .034) but did
      not affect ADP-induced platelet aggregation. These results suggest (1)
      interactions and effects of antiphospholipid antibodies on platelets are agonist
      and concentration dependent and (2) anti-beta(2)GP1 antibodies may inhibit dense
      granule release and/or inhibition of the arachidonic acid pathway.

PMID- 21733941
TI  - Interaction between MMP-9 gene polymorphisms and smoking in relation to
      myocardial infarction in a Uighur population.
AB  - OBJECTIVES: Matrix metalloproteinase 9 (MMP-9) plays a pivotal role in early
      atherosclerosis, vascular remodeling, and development of arterial plaque rupture.
      The potentially functional MMP-9 gene polymorphism may contribute to the
      susceptibility of myocardial infarction (MI). We aimed to investigate the
      association between the interaction of 2 single-nucleotide polymorphisms ([SNPs] 
      1562C>T and R279Q) of the MMP-9 gene and smoking with MI in a Uighur population
      of China. METHODS: A case-control study composed of 384 coronary angiography
      proven patients with MI and 451 sex-matched and ethnically matched control
      participants were enrolled in the study. The genotypes of the 2 selected SNPs
      were determined by the method of polymerase chain reaction and restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: Analysis of 2 SNPs, the
      frequency of -1562 CT and TT genotypes in MI group was significantly higher than
      in control group (25.52% vs 17.29%; P = .004). And the -1562 T allele showed
      significant association with MI (MI vs controls: 14.19% vs 9.31%; P = .002).
      R279Q locus did not show significant differences between patients and controls (
      P > .05). Multiple logistic regression analysis showed that -1562 T allele (CT or
      TT genotype; odds ratio [OR] 1.31, 95% confidence interval [CI] 1.22-1.40; P =
      .004), the interaction between -1562 T allele and smoking (OR 4.42, 95% CI 2.74
      7.13; P < .001), and the interaction between 279 Q allele and smoking (OR 2.07,
      95% CI: 1.04-4.13; P = .021) were independent risk factors for MI. CONCLUSIONS:
      There findings suggest that MMP-9 -1562C>T polymorphism could be associated with
      the susceptibility to MI. Another SNP (R279Q) polymorphism was not significantly
      associated with MI. The -1562C>T or R279Q polymorphism of MMP-9 gene and smoking
      have a synergistic effect and are significantly associated with the risk of MI in
      Chinese Uighur population, respectively.

PMID- 21733942
TI  - Prevention of deep vein thrombosis and pulmonary embolism in patients with
      stroke.
AB  - Venous thromboembolism (VTE), encompassing deep venous thrombosis and pulmonary
      embolism, is a potentially fatal but preventable complication of stroke. Reported
      rates of VTE after stroke have decreased over the last four decades, possibly due
      to the implementation of stroke units, early mobilization and hydration, and
      increased early use of antiplatelets. Additional means of thromboprophylaxis in
      stroke include mechanical methods (ie, compression stockings) to prevent venous
      stasis and medical therapy including antiplatelets, heparins, and heparinoids.
      Risk of VTE must be balanced by potential risk of hemorrhagic complications from
      pharmacotherapy. Unfractionated heparin, low-molecular-weight heparin (LMWH), and
      danaparoid are acceptable options for chemoprophylaxis though none have shown
      superior efficacy for VTE prevention without an associated increase in major
      hemorrhage. The efficacy and timing of pharmacological thromboprophylaxis in
      hemorrhagic stroke are not well defined. Graduated compression stockings are
      associated with an increased rate of adverse events and are not recommended and
      intermittent pneumatic compression stockings require further investigation.

PMID- 21733943
TI  - The role of cognitive appraisal in adaptation to traumatic stress in adults with
      serious mental illness: a critical review.
AB  - A compelling body of literature suggests that negative appraisal may be
      associated with adverse reactions to traumatic stress. However, very few studies
      have examined how appraisal influences posttraumatic adaptation in people with
      serious mental illness (SMI) despite evidence of disproportionately high
      prevalence rates of trauma exposure and Posttraumatic Stress Disorder (PTSD) in
      this population. The purpose of this article is to provide a critical analysis of
      the theoretical and empirical literature on cognitive appraisal and psychological
      adaptation to traumatic stress with a specific focus on individuals diagnosed
      with SMI. It will be argued that appraisal is a key correlate that may partially
      account for higher rates of PTSD in people diagnosed with major mood and
      schizophrenia-spectrum disorders, meriting special consideration for future
      research.

PMID- 21733944
TI  - Reliability of the Baltimore Activity Scale Questionnaire for Intermittent
      Claudication.
AB  - We assessed the reliability of the Baltimore Activity Scale for Intermittent
      Claudication (BASIC) for the evaluation of physical activity levels in
      individuals with intermittent claudication. We also identify the characteristics
      of the patients that influence the reliability of this questionnaire. A total of
      38 men and women with peripheral artery disease and symptoms of intermittent
      claudication participated in the study. BASIC was administered to patients by the
      same evaluator at 2 different visits, separated by 7 days. The concordance
      coefficient ranged from .43 (How often do you walk at a fast pace?) to .85 (What
      happens when you feel pain while you walk?). The concordance coefficient of BASIC
      total score was .60. Higher concordance coefficients were observed in women (.66
      vs .55), in younger patients (.63 vs .56), and in patients with lower ankle
      brachial index (.64 vs .55). The reliability of BASIC questionnaire ranged from
      moderate to good in patients with claudication.

PMID- 21733945
TI  - The association of Raynaud syndrome with thromboangiitis obliterans--a meta
      analysis.
AB  - Thromboangiitis obliterans (TAO) has traditionally been included among the
      diseases associated with Raynaud syndrome (RS). The prevalence of RS in patients
      with TAO is not well defined. The objective of this meta-analysis is to assess
      the prevalence of RS in patients with TAO. A literature search was performed for
      the studies dealing with RS and TAO. The studies provided sufficient data to
      estimate the prevalence of RS in patients with TAO. A total of 8 eligible
      studies, contributing data on 851 patients, were included in this meta-analysis.
      For TAO, a pooled prevalence of 28.1% and 95% confidence interval ([CI] = 0.158,
      0.423) were obtained. Statistically publication bias was not present (P = .232).
      Despite some heterogeneity, there is a possible indication of an association
      between RS and patients with TAO.

PMID- 21733946
TI  - Influence of abnormal fasting plasma glucose on left ventricular function in
      older patients with acute myocardial infarction.
AB  - We assessed whether the admission fasting plasma glucose (FPG) levels were
      associated with all-cause mortality and left ventricular (LV) function in older
      patients with acute myocardial infarction (AMI). A total of 1854 consecutive
      patients were categorized into 4 groups: hypoglycemia, euglycemia, mild
      hyperglycemia, and severe hyperglycemia. The primary outcomes were in-hospital/3
      year mortality and LV function. There was a near-linear relationship between FPG
      and Killip class. However, no significant correlation was found between FPG
      levels and LV ejection fraction. Both FPG levels and Killip classes were all
      independent significant predictors of mortality. Compared with the euglycemia
      group, both the hypo- and hyperglycemia groups were associated with higher in
      hospital and 3-year mortality. In older patients with AMI, the FPG values had
      differential influences on LV function and mortality. There was a U-shaped
      relationship between FPG and in-hospital/3-year mortality, and a near-linear
      relationship between increased admission glucose levels and higher Killip
      classification.

PMID- 21733947
TI  - Prognostic value of mean platelet volume in patients with non-ST-elevation acute
      coronary syndrome.
AB  - The aim of this study is to determine mean platelet volume (MPV) in a population
      with non-ST-elevation acute coronary syndrome (nSTEACS) and explore its relation
      with prognosis. Patients (n = 329) with a diagnosis of nSTEACS at admission were
      recruited, with a determination of MPV in the first 12 hours at admission. We
      also collected blood from 87 healthy controls. A composite end point of
      cardiovascular death and new ACS was assessed at 6-month follow-up. Patients with
      nSTEACS showed larger platelets (MPV: 11.0 [10.3-11.8] vs 9.2 [8.6-10.0] fL; P <
      .001.). In Cox regression analysis, MPV at admission was a significant predictor
      of cardiovascular adverse events in univariate analysis, hazard ratio (HR) 1.4
      95% confidence interval (CI) 1.1-1.8; P = .018; but after adjustment with
      clinical variables, MPV lost its statistical significance. In conclusion,
      patients with nSTEACS present with larger platelets than healthy controls,
      however this parameter did not show an independent prognostic significance at 6
      month follow-up.

PMID- 21733948
TI  - Quality of life of patients with peripheral arterial disease and chronic stable
      angina.
AB  - The Coronary Artery Disease in gENeral practiCE (CADENCE) study examined chronic
      stable angina (CSA). This further analysis examined atherosclerotic risk factors,
      symptomatic status, clinical management, and quality of life in patients with CSA
      with and without peripheral arterial disease (PAD). The CADENCE study involved
      207 Australian general practitioners (GPs) recruiting 10 to 15 consecutively
      presenting patients with CSA (n = 2031). General practitioners completed a 2-page
      case report form, detailing demographic data, cardiovascular status, risk
      factors, and GP perception of control. Patients completed the Seattle Angina
      Questionnaire. Patients with coexisting CSA and PAD (17%) were more likely to be
      older and had more comorbidities than patients with CSA without coexisting PAD.
      Patients with peripheral arterial disease had a longer history of heart disease
      and were more likely to experience angina on a weekly basis. Patients with
      peripheral arterial disease had poorer quality-of-life indices.

PMID- 21733949
TI  - Factors associated with increased carotid intima-media thickness and being
      nondipper in nonobese and normotensive young patients affected by PCOS.
AB  - Polycystic ovary syndrome (PCOS) is characterized by chronic unovulation,
      hyperandrogenism, and insulin resistance. We evaluated factors that affect
      "nondipper" status during 24-hour ambulatory blood pressure monitoring (ABPM) and
      carotid intima-media thickness (cIMT) in PCOS. Forty-two nonobese women newly
      diagnosed as PCOS and 32 healthy women were included. After biochemical and
      hormonal measurements, the ovaries were imaged by pelvic ultrasonography and cIMT
      was measured by B-mode ultrasonography. A 24-hour ABPM was performed thereafter.
      Carotid IMT and the ratio of nondippers were elevated compared with controls.
      Homeostasis model assessment insulin resistance index (HOMA-IR) and low-density
      lipoprotein cholesterol (LDL-C) were found to be related with being a nondipper
      in PCOS. None of the parameters evaluated were found to correlate with cIMT. In
      conclusion, patients with PCOS had increased nondipping ratios and cIMT when
      compared with controls. Insulin resistance and LDL cholesterol are factors that
      are related to diurnal variation in normotensive and young patients with PCOS.

PMID- 21733950
TI  - Frailty across the spectrum of ankle-brachial index.
AB  - We investigated the burden of frailty across the spectrum of ankle-brachial index
      (ABI < 0.9, 0.9 <= ABI < 1.1, 1.1 <= ABI < 1.4 and >=1.4) using data from the
      National Health and Nutritional Examination Survey (NHANES) in respondents aged
      >50 years. Criteria used to identify frailty status included weight loss, slow
      walking speed, weakness, exhaustion, and low physical activity. Participants
      meeting 1 to 2 criteria were classified as prefrail, and those meeting >=3
      criteria were classified as frail. Prevalence of frailty in respondents with ABI
      < 0.9 (17.5%) and 0.9 <= ABI < 1.1 (6.7%) was higher than in participants with
      normal ABI-1.1 <= ABI < 1.4 (4.7%). In multivariable multinomial logistic
      regression models, ABI < 0.9 predicted frailty (odds ratio [OR] = 2.31, 95%
      confidence interval [CI] = 1.08-4.94) and prefrailty (OR = 1.36, 95% CI = 0.90
      2.07). Higher prevalence of frailty was seen in participants with ABI >= 1.4
      (7.3%), P = .39. Frailty predicted general and cardiovascular mortality in
      participants with ABI < 0.9. Frailty mediates increased morbidity and mortality
      seen in peripheral arterial disease (PAD).

PMID- 21733951
TI  - Reperfusion strategies for acute ischemic stroke.
AB  - Stroke remains a major cause of morbidity and mortality worldwide. Despite
      preventive measures, effective management strategies are needed to reduce the
      morbidity and mortality associated with this devastating condition. While the
      management of hemorrhagic stroke is mostly limited to supportive care,
      reperfusion strategies in ischemic stroke have been developed and continue to
      evolve. Conceptually, the pathophysiology of ischemic stroke is similar to that
      of acute myocardial infarction and the objective of management is similar (ie, to
      rapidly restore normal flow to reduce permanent damage). It is, therefore, not
      surprising that the management of acute ischemic stroke includes intravenous (IV)
      thrombolysis, the only Food and Drug Administration (FDA)-approved strategy at
      this point. In addition, there are a myriad of emerging endovascular
      interventional techniques. We review the current literature and discuss some of
      the technical aspects of endovascular therapy in the setting of acute ischemic
      stroke.

PMID- 21733952
TI  - Cilostazol: a pilot study on safety and clinical efficacy in neuropathies of
      diabetes mellitus type 2 (ASCEND).
AB  - BACKGROUND: Diabetic polyneuropathy may have vascular and metabolic components in
      its pathophysiologic mechanism. Cilostazol, aside from its antiplatelet and
      vasodilatory properties, may increase nerve blood flow and potentially improve
      neuropathy. OBJECTIVE: To assess the efficacy and safety of cilostazol in
      diabetic polyneuropathy. METHODS: Forty-seven diabetic patients were randomized
      into placebo, low-dose (100 mg/d), and high-dose (200 mg/d) cilostazol groups.
      Primary efficacy parameter was a change in neuropathy symptom scores and
      secondary efficacy parameter was a change in walking speed from baseline to week
      12. Safety parameters were changes in nerve conduction studies as well as
      reporting of adverse events. RESULTS/CONCLUSION: Despite significant improvement
      in the neuropathy symptom scores in the overall motor and sensory categories of
      the 3 arms of the study from baseline to week 12, no significant differences were
      found among the groups, indicating nonsuperiority of cilostazol in regard to
      improvement of neuropathy symptoms over the short study span. However,
      cilostazol, at low dose, was effective in improving walking speed from baseline
      to week 12, implying an improved blood flow. No significant worsening nor
      improvement in motor and sensory nerve conduction parameters were observed,
      comparing the 3 study arms from baseline to weeks 4, 12, and 16, supporting
      cilostazol's safety. Overall, the adverse events of the 3 study arms did not
      significantly differ, and neither were there serious adverse events reported,
      also signifying safety and tolerability in our Filipino cohort of patients with
      neuropathy in diabetes mellitus treated with cilostazol.

PMID- 21733953
TI  - Differential effects of terlipressin on pulmonary and systemic hemodynamics in
      patients with cirrhosis and pulmonary hypertension: an echo study.
AB  - Terlipressin has been associated with pulmonary arterial vasodilation in patients
      with pulmonary hypertension (PH). We investigated the effects of terlipressin on
      pulmonary vascular resistance (PVR) in patients with cirrhosis without and with
      PH. Pulmonary vascular resistance and cardiac output (CO) by Doppler ultrasound,
      mean arterial pressure (MAP), and systemic vascular resistance (SVR) were
      evaluated in patients with cirrhosis with PVR -120 dyne s cm-5 (group 1, n = 20)
      and PVR >120 dyne s cm-5 (group 2, n = 10) before and 30 minutes after
      terlipressin infusion (2 mg). After terlipressin, PVR increased significantly in
      group 1 (96.1 +/- 20.2 vs 85.1 +/- 18 dyne s cm-5; P = .004) but decreased
      significantly in group 2 (170.4 +/- 37.8 vs 157.8 +/- 28.1 dyne s cm-5; P= .04).
      Pulmonary vascular resistance changes in group 2 correlated significantly with
      baseline PVR (r = -0.632; P = .04). Terlipressin induced a significant increase
      in MAP and SVR and a significant decrease in CO in both groups. Terlipressin
      significantly reduces pulmonary pressures in patients with cirrhosis having PH
      together with systemic hemodynamic improvement.

PMID- 21733954
TI  - Hematologic parameters and angiographic progression of coronary atherosclerosis.
AB  - Hematologic parameters have prognostic importance in cardiovascular disease.
      However, the relation between atherosclerosis progression and hematologic
      parameters is not well defined. A total of 394 patients requiring repeat coronary
      angiography were included in the study. According to angiography, patients were
      divided into 2 groups, progressive (n = 196) and nonprogressive (n = 198)
      diseases. Hematologic parameters including mean platelet volume (MPV) and
      neutrophil/lymphocyte (N/L) ratio were measured. Glucose, creatinine, and
      cholesterol were significantly higher in the progressive group. Mean platelet
      volume count was similar in both groups. The N/L ratio was significantly higher
      in the progressive group (5.0 +/- 5.1 vs 3.2 +/- 3; P = .001). In multivariate
      analysis, the N/L ratio was significantly related with progression (relative risk
      [RR]: 2.267, 95% CI: 1.068-4.815, P = .03). Progression rate was significantly
      high in patients with high N/L ratio (39% vs 56%). Our results suggest that the
      N/L ratio is a predictor of progression of atherosclerosis.

PMID- 21733955
TI  - Transarterial chemoembolization for HCC in patients with extensive liver
      transplantation waiting times.
AB  - The treatment of hepatocellular cancer (HCC) with transarterial chemoembolization
      (TACE) prior to orthotopic liver transplant (OLT) is of increasing importance due
      to the rise in HCC incidence and donor shortage. This single-center study
      examines 28 patients treated with TACE and 7 patients not treated with TACE, with
      HCC prior to OLT between 1999 and 2008. The overall 1- and 5-year survival of all
      transplanted patients with HCC was 94% (33 of 35) and 80% (28 of 35). There was
      no difference in survival (P = .99) between patients who underwent
      transplantation immediately (median 95 days) and patients who had significantly
      longer wait times (median 308 days) when treated with TACE. During extensive wait
      times for OLT, TACE can be used to keep patients with HCC on the waiting list by
      preventing tumor progression, with similar outcomes compared with those who
      underwent transplantation immediately.

PMID- 21733956
TI  - Commuting to work: RN travel time to employment in rural and urban areas.
AB  - PURPOSE: To investigate the variation in average daily travel time to work among
      registered nurses (RNs) living in urban, suburban, and rural areas. We examine
      how travel time varies across RN characteristics, job setting, and availability
      of local employment opportunities. METHOD: Descriptive statistics and linear
      regression using a 5% sample from the 2000 Census and a longitudinal survey of
      newly licensed RNs (NLRN). Travel time for NLRN respondents was estimated using
      geographic information systems (GIS) software. FINDINGS: In the NLRN, rural
      nurses and those living in small towns had significantly longer average commute
      times. Young married RNs and RNs with children also tended to have longer commute
      times, as did RNs employed by hospitals. CONCLUSIONS: The findings indicate that
      travel time to work varies significantly across locale types. Further research is
      needed to understand whether and to what extent lengthy commute times impact RN
      workforce needs in rural and urban areas.

PMID- 21733957
TI  - The potential public health effects of a police announcement about HIV
      nondisclosure: a case scenario analysis.
AB  - In May 2010, a local police force released the details of an HIV-transmission
      related criminal investigation. This involved the publication of the name and
      photograph of, and charges against a man who the police allege did not disclose
      his HIV status prior to engaging in sexual activities that pose a "significant
      risk" for HIV transmission. Presently, however, there are no public health
      analyses of this situation. Consequently, the available literature on Canadian
      criminal laws, HIV transmission within this jurisdiction, and HIV prevention are
      presented and discussed herein. The outcome of this analysis is the conclusion
      that the act of publicizing an HIV-related criminal investigation more likely
      inhibits than encourages STI/HIV testing among HIV-negative and HIV-positive men
      who have sex with men. It is the assertion here that this undertaking thus
      conflicts with the overall public health goals of HIV prevention, and should
      likely not occur in the future.

PMID- 21733958
TI  - Early indicators of autism spectrum disorders at 12 and 24 months of age: a
      prospective, longitudinal comparative study.
AB  - Prospective questionnaire data from a longitudinal population sample on children
      with autism spectrum disorders (ASD), developmental delay, specific language
      impairment, or typical development (TD), were collected at ages eight, 12 and 24
      months, via the Communication and Symbolic Behavior Scale Developmental Profile
      (CSBS) - Infant Toddler Checklist, and the Actions and Gesture section of the
      MacArthur-Bates Communicative Development Inventory (CDI):Words and Gestures. The
      four groups were compared at four years of age to identify whether any early
      behaviours differentiated the groups. While children with ASD differed from TD
      children on most social communicative measures by 12 months of age, the only
      social communication characteristic which could differentiate the children with
      ASD from the other groups were gesture scores on the CDI at 12 months and the
      CSBS at 24 months. Significant markers of ASD were identifiable in this community
      sample at an early age, although discrimination between clinical groups was
      rarely evident.

PMID- 21733959
TI  - Emotion regulation and internalizing symptoms in children with autism spectrum
      disorders.
AB  - The aim of this study was to examine the unique contribution of two aspects of
      emotion regulation (awareness and coping) to the development of internalizing
      problems in 11-year-old high-functioning children with an autism spectrum
      disorder (HFASD) and a control group, and the moderating effect of group
      membership on this. The results revealed overlap between the two groups, but also
      significant differences, suggesting a more fragmented emotion regulation pattern
      in children with HFASD, especially related to worry and rumination. Moreover, in
      children with HFASD, symptoms of depression were unrelated to positive mental
      coping strategies and the conviction that the emotion experience helps in dealing
      with the problem, suggesting that a positive approach to the problem and its
      subsequent emotion experience are less effective in the HFASD group.

PMID- 21733960
TI  - Empirical and normative ethics: a synthesis relating to the care of older
      patients.
AB  - The aim of this study was to synthesize the concepts from empirical studies and
      analyze, compare and interrelate them with normative ethics. The International
      Council of Nurses (ICN) and the Health and Medical Service Act are normative
      ethics. Five concepts were used in the analysis; three from the grounded theory
      studies and two from the theoretical framework on normative ethics. A
      simultaneous concept analysis resulted in five outcomes: interconnectedness,
      interdependence, corroboratedness, completeness and good care are all related to
      the empirical perspective of the nurse's interaction with the older patient, and
      the normative perspective, i.e. that found in ICN code and SFS law. Empirical
      ethics and normative ethics are intertwined according to the findings of this
      study. Normative ethics influence the nurse's practical performance and could be
      supporting documents for nurses as professionals.

PMID- 21733961
TI  - Changing constantly and constant change.

PMID- 21733963
TI  - The relationship between gender segregation in the workplace and long-term
      sickness absence in Sweden.
AB  - BACKGROUND: The aim of the study is to investigate whether the gender composition
      in workplaces is related to long-term sickness absence (LSA). We start off with
      Kanter's theory on ''tokenism,'' suggesting an increased risk of stress among
      minority groups (tokens), which, in turn, might increase the risk of ill health
      and LSA. METHODS: The dataset consists of information obtained from the Swedish
      level of Living Survey (LNU) and the Swedish Establishment Survey (APU), linked
      to register-based data from the Swedish Social Insurance Agency. The longitudinal
      data is representative for the Swedish population and consists of 496 women and
      566 men, aged 20-55 at baseline. Our study group consisted of employed persons in
      1991 and we analyze, by means of piecewise constant intensity regressions, the
      first entry into LSA with a follow-up period of nine years. RESULTS: Compared
      with women in gender-integrated workplaces, women's risk of LSA is most elevated
      at both extremely male-dominated (0-20% females) and extremely female-dominated
      workplaces (80-100% females), although the result among women in the most male
      dominated group did not reach statistical significance at the 5% level. Men's
      risk seems less varied by gender composition. CONCLUSIONS: The present study
      suggests that the gender composition in the workplace has an impact on the risk
      of LSA, especially among women. Our findings lend no support for Kanter's theory
      on the effects of being a token. Most likely, women's and men's different status
      positions have an impact on the different associations found.

PMID- 21733964
TI  - Acinetobacter baumannii isolates from pets and horses in Switzerland: molecular
      characterization and clinical data.
AB  - OBJECTIVES: We investigated whether Acinetobacter baumannii isolates of
      veterinary origin shared common molecular characteristics with those described in
      humans. METHODS: Nineteen A. baumannii isolates collected in pets and horses were
      analysed. Clonality was studied using repetitive extragenic palindromic PCR (rep
      PCR) and multilocus sequence typing (MLST). PCR and DNA sequencing for various
      beta-lactamase, aminoglycoside-modifying enzyme, gyrA and parC, ISAba1 and
      IS1133, adeR and adeS of the AdeABC efflux pump, carO porin and class 1/2/3
      integron genes were performed. RESULTS: Two main clones [A (n = 8) and B (n = 9)]
      were observed by rep-PCR. MLST indicated that clone A contained isolates of
      sequence type (ST) ST12 (international clone II) and clone B contained isolates
      of ST15 (international clone I). Two isolates of ST10 and ST20 were also noted.
      Seventeen isolates were resistant to gentamicin, 12 to ciprofloxacin and 3 to
      carbapenems. Isolates of ST12 carried bla(OXA-66), bla(ADC-25), bla(TEM-1), aacC2
      and IS1133. Strains of ST15 possessed bla(OXA-69), bla(ADC-11), bla(TEM-1) and a
      class 1 integron carrying aacC1 and aadA1. ISAba1 was found upstream of bla(ADC)
      (one ST10 and one ST12) and/or bla(OXA-66) (seven ST12). Twelve isolates of
      different STs contained the substitutions Ser83Leu in GyrA and Ser80Leu or
      Glu84Lys in ParC. Significant disruptions of CarO porin and overexpressed efflux
      pumps were not observed. The majority of infections were hospital acquired and in
      animals with predisposing conditions for infection. CONCLUSIONS: STs and the
      molecular background of resistance observed in our collection have been
      frequently described in A. baumannii detected in human patients. Animals should
      be considered as a potential reservoir of multidrug-resistant A. baumannii.

PMID- 21733965
TI  - High prevalence of extended-spectrum beta-lactamases and qnr determinants in
      Citrobacter species from Japan: dissemination of CTX-M-2.
AB  - OBJECTIVES: Extended-spectrum beta-lactamases (ESBLs) have become a problem among
      AmpC-producing Enterobacteriaceae and the emergence of concomitant quinolone
      resistance in beta-lactamase-producing isolates poses a global threat. In this
      study we investigated the prevalence and regional variation of ESBLs in Japanese
      clinical isolates of Citrobacter spp. and analysed plasmid-mediated quinolone
      resistance (PMQR) determinants in ESBL-producing Citrobacter spp. METHODS: A
      total of 348 clinical isolates of Citrobacter spp. collected throughout Japan
      were studied. Screening and the boronic acid disc test were performed to detect
      ESBLs in Citrobacter spp. with chromosomal AmpC beta-lactamases. PCR and
      sequencing were done to identify ESBL and PMQR genes. For ESBL-producing
      Citrobacter spp., PFGE was performed using the SfiI restriction enzyme. RESULTS:
      The number of ESBL-producing isolates confirmed phenotypically was 67 (19.3%).
      The prevalence of ESBL-producing Citrobacter koseri was significantly higher
      (32.1%) than that of ESBL-producing Citrobacter freundii (4.6%) (P < 0.01).
      Moreover, the prevalence of ESBLs was notably higher among C. koseri from
      southern Japan (60.0%). CTX-M-2 was predominant in C. koseri. Of the ESBL
      producing C. koseri analysed, 23.2% possessed PMQR determinants, and there was a
      significant association between qnrB4 and bla(SHV-12). The 57 ESBL-producing
      Citrobacter spp. possessing bla(CTX-M), bla(SHV) or bla(TEM) were divided into 18
      unique PFGE types. CONCLUSIONS: This is the first report about the prevalence of
      PMQR determinants among ESBL-producing Citrobacter spp. from Japan. Our data
      suggest that ESBLs and PMQR determinants are spreading among C. koseri in Japan.

PMID- 21733966
TI  - Comparison of the bactericidal activity of various fluoroquinolones against
      Mycobacterium tuberculosis in an in vitro experimental model.
AB  - OBJECTIVES: To compare the bactericidal activity of various fluoroquinolones
      against Mycobacterium tuberculosis in the latent and exponential growth phases.
      METHODS: Ciprofloxacin, levofloxacin and moxifloxacin were tested against 16 M.
      tuberculosis clinical isolates (4 resistant and 12 susceptible to
      fluoroquinolones) from Elche, Spain, isolated between 1992 and 2009. To study
      bactericidal activity, an inoculum of approximately 10(5) cfu of each isolate was
      cultured in Middlebrook 7H9 broth. The broth was previously acidified to pH 4.6
      to obtain the microorganism in the stationary phase. Cultures with different
      concentrations (0.1 to 50 mg/L) of antibiotic and antibiotic-free controls were
      incubated for 48 h then plated onto Middlebrook 7H11 to detect bacterial killing.
      In all stages of the process the M. tuberculosis strain ATCC 41323 was included
      as a quality control to ensure reproducible results. RESULTS: Moxifloxacin and
      levofloxacin were found to exhibit bactericidal activity at lower concentrations
      and against more strains in both the latent and the exponential growth phases
      compared with ciprofloxacin. The bactericidal activity of moxifloxacin was
      greater than that of levofloxacin against microorganisms in the exponential
      growth phase, but the opposite was true in the latent phase. CONCLUSIONS: Our
      data confirm the usefulness of moxifloxacin in the treatment of tuberculosis and
      suggest that levofloxacin may be used as an alternative drug in the treatment of
      latent tuberculosis when it is not possible to use isoniazid. Based on the
      results presented, ciprofloxacin appears to be a poor choice.

PMID- 21733967
TI  - Thoracic facet joint synovitis causing thoracic spinal cord compression and
      myelopathy in a patient with rheumatoid arthritis.

PMID- 21733969
TI  - What does imaging tell us about polymyalgia rheumatica?

PMID- 21733968
TI  - Inequalities in primary care management of knee pain and disability in older
      adults: an observational cohort study.
AB  - OBJECTIVES: To describe primary care management of knee pain, in relation to
      National Institute for Health and Clinical Excellence (NICE) OA guidelines, and
      examine variation in management by patient characteristics. METHODS: Subjects
      were 755 adults aged >=50 years who responded to baseline and 3-year surveys and
      had consulted primary care for knee pain. Medical records (1997-2006) were
      searched. Associations of having interventions from the outer circle (adjunctive
      treatments or Step 3) of the NICE guidelines with self-reported socio-demographic
      and knee-specific factors were determined. RESULTS: Eighty per cent had received
      a Step 3 intervention. Thirty-eight per cent had been referred to secondary care,
      and 10% had received a knee replacement. Forty-three per cent had been prescribed
      an opioid and 41% an NSAID. Severe knee pain or disability at baseline and follow
      up was the main association with receiving a Step 3 intervention [adjusted odds
      ratio (OR) 2.26; 95% CI 1.38, 3.70] and with referral (OR 2.57; 95% CI 1.72,
      3.83). Older patients were less likely to be referred. Although non-significant,
      those of higher social class, in more affluent areas, older age or overweight or
      obese, appeared more likely to receive a knee replacement. Fifty per cent of
      those reporting severe knee pain or disability in both surveys had not been
      referred to secondary care. CONCLUSION: Most of the older adults who consult
      primary care with knee pain receive at least one Step 3 intervention from the OA
      guidelines. Inequalities in the management and referral of knee problems in
      primary care were generally not observed, although there were some trends towards
      differences in likelihood of total knee replacement.

PMID- 21733970
TI  - Impaired hippocampal long-term potentiation and failure of learning in beta1,4-N
      acetylgalactosaminyltransferase gene transgenic mice.
AB  - Gangliosides (sialic acid-containing glycosphingolipids) play important roles in
      many physiological functions, including synaptic plasticity in the hippocampus,
      which is considered as a cellular mechanism of learning and memory. In the
      present study, three types of synaptic plasticity, long-term potentiation (LTP),
      long-term depression (LTD) and reversal of LTP (depotentiation, DP), in the field
      excitatory post-synaptic potential in CA1 hippocampal neurons and learning
      behavior were examined in beta1,4-N-acetylgalactosaminyltransferase (beta1,4
      GalNAc-T; GM2/GD2 synthase) gene transgenic (TG) mice, which showed a marked
      decrease in b-pathway gangliosides (GQ1b, GT1b and GD1b) in the brain and
      isolated hippocampus compared with wild-type (WT) mice. The magnitude of the LTP
      induced by tetanus (100 pulses at 100 Hz) in TG mice was significantly smaller
      than that in control WT mice, whereas there was no difference in the magnitude of
      the LTD induced by three short trains of low-frequency stimulation (LFS) (200
      pulses at 1 Hz) at 20 min intervals between the two groups of mice. The reduction
      in the LTP produced by delivering three trains of LFS (200 pulses at 1 Hz, 20 min
      intervals) was significantly greater in the TG mice than in the WT mice. Learning
      was impaired in the four-pellet taking test (4PTT) in TG mice, with no
      significant difference in daily activity or activity during the 4PTT between TG
      and WT mice. These results suggest that the overexpression of beta1,4 GalNAc-T
      resulted in altered synaptic plasticity of LTP and DP in hippocampal CA1 neurons
      and learning in the 4PTT, and this is attributable to the shift from b-pathway
      gangliosides to a-pathway gangliosides.

PMID- 21733974
TI  - A new AURKC mutation causing macrozoospermia: implications for human
      spermatogenesis and clinical diagnosis.
AB  - The presence of close to 100% large-headed multi-tailed spermatozoa in the
      ejaculate has been described as a rare phenotype of male infertility with a very
      poor prognosis. We demonstrated previously that most cases were caused by a
      homozygous mutation (c.144delC) in the Aurora Kinase C gene (AURKC) leading to
      the absence or the production of a non-functional protein. AURKC deficiency in
      these patients blocked meiosis and resulted in the production of tetraploid
      spermatozoa unsuitable for fertilization. We describe here the study of two
      brothers presenting with large-headed spermatozoa. Molecular analysis of the
      AURKC gene was carried out in two brothers presenting with a typical large-headed
      spermatozoa phenotype. Both affected brothers were heterozygous for the c.144delC
      mutation. After complete sequencing of the gene a new heterozygous variant, c.436
      2A>G, was identified in both patients. This mutation is located in the acceptor
      consensus splice site of exon 5. AURKC transcripts were extracted from one of the
      patient's leukocytes and reverse transcription polymerase chain reaction could be
      realized showing the presence of a truncated transcript indicating that c.436
      2A>G leads to the skipping of exon 5. These results indicate that AURKC molecular
      analysis of patients with large-headed spermatozoa should not be stopped in the
      absence of a homozygous recurrent mutation on exon 3 but complete sequence
      analysis should be performed. This diagnosis is important as the identification
      of AURKC mutations in patients indicates that all spermatozoa will be
      chromosomally abnormal and that ICSI should not be attempted.

PMID- 21733975
TI  - Management of acute infective conjunctivitis.
AB  - Eye conditions account for 2-5% of all consultations in general practice.1 One
      third of these eye problems (equivalent to around 13-14 cases per 1,000
      population per year) are cases of infective conjunctivitis, normally a self
      limiting condition.2,3 Traditionally, topical antibacterials have been prescribed
      for people with acute infective conjunctivitis.4 In 2005, chloramphenicol eye
      drops became available over the counter (OTC) from UK pharmacies as a treatment
      for conjunctivitis, and there is evidence that the overall use of chloramphenicol
      for this indication has increased since then.5 Here we review the evidence on the
      efficacy of antibacterials in acute infective conjunctivitis. We also offer
      practical information and advice for prescribers and community pharmacists on
      managing patients with the condition.

PMID- 21733976
TI  - Distinct carbohydrate and lipid-based molecular patterns within
      lipopolysaccharides from Burkholderia cepacia contribute to defense-associated
      differential gene expression in Arabidopsis thaliana.
AB  - Lipopolysaccharides are structural components within the cell walls of Gram
      negative bacteria. The LPSs as microbe-associated molecular pattern (MAMP)
      molecules can trigger defense-related responses involved in MAMP-triggered
      immunity and basal resistance in plants, presumably from an initial perception
      event. LPS from Burkholderia cepacia as well as two fragments, the glycolipid,
      lipid A and the polysaccharide (OPS-core) chain, were used to treat Arabidopsis
      thaliana seedlings to evaluate the eliciting activities of the individual LPS sub
      domains by means of Annealing Control Primer-based Differential Display
      transcript profiling. Genes found to be up-regulated encode for proteins involved
      in signal perception and transduction, transcriptional regulation and defense -
      and stress responses. Furthermore, genes encoding proteins involved in
      chaperoning, secretion, protein-protein interactions and protein degradation were
      differentially expressed. It is concluded that intact LPS, as well as the two sub
      components, induced the expression of a broad range of genes associated with
      perception and defense as well as metabolic reprogramming of cellular activities
      in support of immunity and basal resistance. Whilst the lipid A and OPS moieties
      were able to up-regulate sub-sets of defense-associated genes over the same
      spectrum of categories as intact LPS, the up-regulation observed with intact LPS
      was the more comprehensive, suggesting that the lipid A and glycan molecular
      patterns of the molecule act as partial agonists, but that the intact LPS
      structure is required for full agonist activity.

PMID- 21733977
TI  - Rotavirus-induced IFN-beta promotes anti-viral signaling and apoptosis that
      modulate viral replication in intestinal epithelial cells.
AB  - Rotavirus (RV), a leading cause of diarrhea, primarily infects intestinal
      epithelial cells (IEC). Rotavirus-infected IEC produce IFN-beta and express
      hundreds of IFN-dependent genes. We thus hypothesized that type 1 IFN plays a key
      role in helping IEC limit RV replication and/or protect against cell death. To
      test this hypothesis, we examined IEC (HT29 cells) infected with RV (MOI 1) +/-
      neutralizing antibodies to IFN-alpha/beta via microscopy and SDS-PAGE
      immunoblotting. We hypothesized that neutralization of IFN would be clearly
      detrimental to RV-infected IEC. Rather, we observed that blockade of IFN function
      rescued IEC from the apoptotic cell death that otherwise would have occurred 24
      48 h following exposure to RV. This resistance to cell death correlated with
      reduced levels of viral replication at early time points (< 8 h) following
      infection and eventuated in reduced production of virions. The reduction in RV
      replication that resulted from IFN neutralization correlated with, and could be
      recapitulated by, blockade of IFN-induced protein kinase R (PKR) activation,
      suggesting involvement of this kinase. Interestingly, pharmacologic blockade of
      caspase activity ablated RV-induced apoptosis and dramatically increased viral
      protein synthesis, suggesting that IFN-induced apoptosis helps to control RV
      infection. These results suggest non-mutually exclusive possibilities that IFN
      signaling is usurped by RV to promote early replication and induction of cell
      death may be a means by which IFN signaling possibly clears RV from the
      intestine.

PMID- 21733978
TI  - Clinical audit: a useful tool for reducing severe postpartum haemorrhages?
AB  - OBJECTIVE: Reducing the rate of severe postpartum haemorrhage (PPH) is a major
      challenge in obstetrics today. One potentially effective tool for improving the
      quality of care is the clinical audit, that is, peer evaluation and comparison of
      actual practices against explicit criteria. Our objective was to assess the
      impact of regular criteria-based audits on the prevalence of severe PPH. DESIGN:
      Quasi-experimental before-and-after survey. SETTING: Two French maternity units
      in the Rhone-Alpes region, with different organization of care. PARTICIPANTS: All
      staff of both units. INTERVENTION: Quarterly clinical audit meetings at which a
      team of reviewers analysed all cases of severe PPH and provided feedback on
      quality of care and where all staff actively participated. MAIN OUTCOME MEASURES:
      The primary outcome was the prevalence of severe PPH. Secondary outcomes included
      the global quality of care for women with severe PPH, including the performance
      rate for each recommended procedure. Differences in these variables between 2005
      and 2008 were tested. RESULTS: The prevalence of severe PPH declined
      significantly in both units, from 1.52 to 0.96% of deliveries in the level III
      hospital (P = 0.048) and from 2.08 to 0.57% in the level II hospital (P < 0.001).
      From 2005 to 2008, the proportion of deliveries with severe PPH that was managed
      consistently with the guidelines increased for all of its main components, in
      both units. CONCLUSION: Regular clinical audits of cases severe PPH were
      associated with a persistent reduction in the prevalence of severe PPH.

PMID- 21733979
TI  - Does spirometry training in general practice improve quality and outcomes of
      asthma care?
AB  - OBJECTIVE: Clinical asthma guidelines recommend spirometry for asthma diagnosis,
      but there is inconsistent evidence about benefits to patients in using it for
      ongoing management. Our aim was to determine whether training in the use of
      spirometry for management of asthma provided better health outcomes and improved
      the quality of care in the primary care setting. DESIGN: Pragmatic, cluster
      randomized controlled trial. SETTING: General practices in two states of
      Australia. PARTICIPANTS: Forty practices and 397 adults with asthma.
      INTERVENTION: The staff of 26 intervention practices received comprehensive
      spirometry training. Fourteen control practices provided usual care. MAIN OUTCOME
      MEASURES: Primary outcome measures were quality of life, self-reported asthma
      symptoms and lung function. Secondary measures related to the process of care
      (e.g. performance of spirometry, preparation of a written asthma action plan) and
      patient and general practitioner rating of the acceptability and usefulness of
      spirometry. RESULTS: There were no statistically significant differences between
      the groups at 12 months for quality of life (mean difference = -0.23; 95% CI: 
      0.44, -0.01), days off work (rate ratio = 1.52; 95% CI: 0.91, 2.54),
      exacerbations (rate ratio = 1.09; 95% CI: 0.85, 1.41), asthma on waking (rate
      ratio = 1.21; 95% CI: 0.79, 1.85), nocturnal asthma (rate ratio = 0.98; 95% CI:
      0.63, 1.51) and post-bronchodilator FEV(1)/FVC ratio (mean difference = -0.01,
      95% CI: -0.03, 0.02). There was no improvement in the quality of care provided.
      CONCLUSIONS: Training in spirometry did not result in any measurable improvement
      in the use of spirometry, quality of management of asthma or patient outcomes in
      primary care.

PMID- 21733980
TI  - Increased live birth rates with GnRH agonist addition for luteal support in
      ICSI/IVF cycles: a systematic review and meta-analysis.
AB  - BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate
      whether the addition of GnRH agonist for luteal support in ICSI/IVF cycles
      enhances the probability of live birth. METHODS: Systematic literature search
      (MEDLINE, EMBASE, CENTRAL and RCT registries) was conducted to identify relevant
      randomized controlled trials published as full manuscripts. Meta-analysis of data
      yielded pooled risk differences (RDs) and 95% confidence intervals (CIs). A
      random effects model was applied for pooling the studies. RESULTS: Six relevant
      RCTs were identified including a total of 2012 patients. The probability of live
      birth rate (RD: +16%, 95% CI: +10 to +22%) was significantly higher in patients
      who received GnRH agonist support compared with those who did not. The subgroup
      analysis according to the type of GnRH analogue used for LH suppression did not
      change the effect observed (studies in which GnRH agonist was used during ovarian
      stimulation, RD: +15%, 95% CI: +5 to +23%); (studies in which GnRH antagonist was
      used during ovarian stimulation, RD: +19%, 95% CI: +11 to +27%). CONCLUSIONS: The
      best available evidence suggests that GnRH agonist addition during the luteal
      phase significantly increases the probability of live birth rates.

PMID- 21733981
TI  - The translational challenge in the development of new and effective therapies for
      endometriosis: a review of confidence from published preclinical efficacy
      studies.
AB  - BACKGROUND: Endometriosis is a benign gynaecological condition that presents
      symptoms of chronic pelvic pain and the ectopic growth of endometrial lesions at
      sites on the peritoneum. Few new approaches to the management of the disease
      symptoms and progression have emerged in decades. The cornerstone of developing
      new therapies is the confidence and translational value placed in the preclinical
      models used to assess efficacy of emerging approaches. METHODS: We systematically
      reviewed preclinical efficacy data from rodent and non-human primates, evaluating
      the effects of an investigational agent or target reported in PubMed between 2000
      and 2010. We evaluated the reports for which model and end-points had been used
      to determine efficacy, whether there was evidence of independent replication,
      whether techniques had been incorporated into the experimental design to
      eliminate potential bias and whether there was a confirmation of drug exposure or
      target engagement in the study. RESULTS: We identified 94 publications that met
      our criteria for review. Efficacy studies were conducted in a wider range of
      different models with no clear consensus on which model or end-point has the most
      translational value. The large majority of studies either did not report what
      measures were incorporated into the design to address potential bias or account
      for it or did not confirm whether the specified target was engaged. CONCLUSIONS:
      Greater scrutiny of the preclinical efficacy models, end-points and experimental
      designs is needed if the desire of translating novel treatment approaches is to
      be realized for women with endometriosis.

PMID- 21733982
TI  - A novel molecular mechanism for nitrated {alpha}-synuclein-induced cell death.
AB  - Although previous studies have demonstrated the involvement of nitrated alpha
      synuclein in neurodegenerative disorders (synucleinopathies), the effects of
      nitrated alpha-synuclein and the molecular mechanisms underlying its toxicity are
      still unclear. In the present study, nitrated alpha-synuclein with four 3
      nitrotyrosines (Tyr(39), Tyr(125), Tyr(133), and Tyr(136)) was obtained non
      enzymatically by incubation with nitrite. The nitrated protein existed as a
      mixture of monomers, dimers, and polymers in solution. The nitrated alpha
      synuclein could induce cell death in a time- and concentration-dependent manner
      when SH-SY5Y cells (a human neuroblastoma cell line) were incubated with the
      dimers and polymers. Treatment with anti-integrin alpha5beta1 antibody partially
      rescued the SH-SY5Y cells from the cell death. Dot blotting and
      immunoprecipitation revealed that the nitrated protein bound to integrin on the
      cell membranes. Level of nitric oxide (NO) and calcium-independent inducible NO
      synthase (iNOS) activity increased during the initial stages of the treatment.
      The expression of phosphorylated focal adhesion kinase (FAK) decreased in the
      cells. Subsequently, an increase in caspase 3 activity was observed in SH-SY5Y
      cells. Our results demonstrate that activation of iNOS and inhibition of FAK may
      both be responsible for the cell death induced by nitrated alpha-synuclein. These
      data suggest that the cytotoxicity of nitrated alpha-synuclein is mediated via an
      integrin-iNOS/-FAK signaling pathway, and that the nitration of alpha-synuclein
      plays a role in neuronal degeneration.

PMID- 21733984
TI  - Improvement of heart rate variability by eurythmy therapy after a 6-week eurythmy
      therapy training.
AB  - BACKGROUND: Eurythmy therapy (EYT) is a mind-body therapy used in anthroposophic
      medicine. Recently, the authors were able to show that at comparable workloads,
      EYT stimulated heart rate variability (HRV) whereas conventional ergometer
      training attenuated HRV. Furthermore, a long-term improvement of quality of life
      (QoL) and stress coping strategies by EYT could be shown. OBJECTIVE: This study
      aimed to evaluate the long-term effects of EYT training on HRV. DESIGN: A total
      of 23 healthy women (mean age = 44.57 +/- 8.04 years) performed 10 hours of EYT
      over a period of 6 weeks. Electrocardiograms were recorded before and after the
      EYT trial. HRV was quantified by the extent of high (HF), low (LF), very low
      (VLF), and ultra low frequency (ULF) oscillations of heart rate. RESULTS:
      Autonomic regulation was significantly changed following the EYT training
      compared with baseline. Especially the proportion referring to the total power
      (P) of HF/P and LF/P increased, whereas ULF/P and (ULF+VLF)/P decreased after the
      training period. CONCLUSION: EYT shifted the autonomic regulation proportionally
      referring to the total power mainly caused by changes of ULF and VLF components
      of HRV. The LF and HF spectral components were also decreased following EYT while
      their proportion in relation to the total variance of the power spectrum was
      increased. The proportional enhancement of the higher frequency and the decrease
      of the ULF and VLF components are probably an indicator of an improvement of
      autonomic regulation processes by more relaxed physical activity after the EYT
      training, thus supporting the plausibility of the improved QoL and better stress
      coping strategies.

PMID- 21733985
TI  - Chemotherapeutic effects of bioassay-guided extracts of the American cockroach,
      Periplaneta americana.
AB  - The organic extract of Periplaneta americana L. (Dictyoptera; Blattidae) has been
      traditionally used in southwestern China as an alternative medicine against
      disorders such as hepatitis, trauma, gastric ulcers, burns, and heart disease.
      The present study describes bioassay-guided purification and chemotherapeutic
      evaluation of the 60% ethanolic fraction of P americana organic extracts (PAE60).
      The most effective cytotoxic fraction was determined by way of repeated in vitro
      screenings against 12 distinct cultured human carcinoma cell lines: Eca 109,
      BGC823, HO8910, LS174T, CNE, HeLa, K562, PC-3, A549, BEL 7404, HL-60, and KB,
      followed by in vivo antitumor assays of the lead fraction (PAE60). The complexity
      of enriched active fraction was qualitatively evaluated using thin layer
      chromatography. Reconstituted PAE60 was effective at inhibiting HL-60, KB, CNE,
      and BGC823 cell growth with IC(50) values <20 ug mL-(1). PAE60 reduced tumor
      growth in S180-bearing immunocompetent mice by 72.62% after 10 days following
      oral doses of 500 mg kg d-(1) compared with 78.75% inhibition following 40 mg kg
      d-(1) of cyclophosphamide (CTX). Thymus and spleen indices of S180-bearing mice
      treated with PAE60 were significantly greater (P < .05) than CTX treatment
      groups, suggesting potential immunomodulation of antitumor host defenses by
      PAE60. Antiviral activity was also investigated and PAE60 inhibited herpes
      simplex type-2 replication (IC(50) = 4.11 +/- 0.64 ug mL-(1)) with a selectivity
      index (CC(50) to IC(50) ratio) of 64.84 in Vero cells but was less effective on
      type-1 virus (IC(50) of 25.6 +/- 3.16 ug mL-(1)). These results support future
      clinical trials on P. americana as an alternative or complementary medicinal
      agent.

PMID- 21733986
TI  - Inhibition of radiation-induced DNA damage by jamun, Syzygium cumini, in the
      cultured splenocytes of mice exposed to different doses of gamma-radiation.
AB  - The radioprotective property of 50 mg/kg body weight jamun (Syzygium cumini)
      extract was studied in the cultured splenocytes of mice exposed to 0, 0.5, 1, 2,
      3, or 4 Gy of gamma-radiation. The spleens of irradiated mice were removed
      aseptically and the splenocytes were extracted from the individual spleens and
      cultured. The micronuclei were prepared 72 hours after irradiation in binucleate
      splenocytes by blocking cytokinesis with cytochalasin-B. Irradiation of mice
      resulted in a dose-dependent elevation in the micronucleated splenocytes. The
      exposure of mice not only elevated splenocytes bearing one micronucleus but also
      cells bearing 2 and multiple (>2) micronuclei indicating induction of complex DNA
      damage after irradiation. Oral treatment of mice with 50 mg/kg body weight of
      jamun leaf extract protected against the radiation-induced micronuclei formation.
      Jamun extract also protected against the formation of 2 and multiple micronuclei
      indicating repair or inhibition of complex DNA damage. The assessment of lipid
      peroxidation in mice brain homogenate has indicated a concentration dependent
      inhibition of lipid peroxidation by jamun extract. Studies in a cell free system
      revealed that jamun extract inhibited the formation of OH, O(2)-, DPPH, and
      ABTS(+) free radicals in a concentration dependent manner. Our study demonstrates
      that jamun extract protected mice against the radiation-induced DNA damage and
      inhibition of radiation-induced free radical formation may be one of the
      mechanisms of radioprotection.

PMID- 21733987
TI  - An exploratory study on the quality of life and individual coping of cancer
      patients during mistletoe therapy.
AB  - BACKGROUND: Although several clinical studies have shown that mistletoe therapy
      (MT, Viscum album) may improve cancer patients' quality-of-life (QoL),
      qualitative information on the improvement's nature is still lacking. DESIGN:
      This exploratory, prospective, cohort-study comprised 25 patients with different
      types of cancer. The patients filled in the EORTC QLQ-C30 Version 3.0
      questionnaire at the beginning of MT (n = 25) and three months later (n = 21). If
      patients agreed, they were interviewed on both occasions (n = 17); the interviews
      were transcribed verbatim and submitted to a qualitative content analysis (n =
      12). RESULTS: Analysis of the questionnaires showed significant improvements in
      several subscales during MT. The interviews analysis revealed that most patients
      adopted the MT with a supportive goal, with all patients undergoing conventional
      therapies. After three months of MT, most interviewed patients revealed higher
      vitality and autonomy. MT was often seen as a chance to make an own personal
      contribution to the therapy, which was particularly appreciated in cases in which
      no conventional therapy was (anymore) advised. Concrete personal achievements
      such as changes in the private and/or in the professional environment were
      spontaneously mentioned by the patients, illustrating and corroborating their
      improvements in QoL. CONCLUSION: Our results show that the patients experienced
      an improvement of QoL during MT. This therapy seemed to offer a platform for an
      integrative coping with the disease, which might be important in reconciling the
      perceived shock of an existential illness with a good QoL.

PMID- 21733988
TI  - Impact of yoga on functional outcomes in breast cancer survivors with aromatase
      inhibitor-associated arthralgias.
AB  - Arthralgia affects postmenopausal breast cancer survivors (BCSs) receiving
      aromatase inhibitors (AIs). This study aims to establish the feasibility of
      studying the impact of yoga on objective functional outcomes, pain, and health
      related quality of life (HR-QOL) for AI-associated arthralgia (AIAA).
      Postmenopausal women with stage I to III breast cancer who reported AIAA were
      enrolled in a single-arm pilot trial. A yoga program was provided twice a week
      for 8 weeks. The Functional Reach (FR) and Sit and Reach (SR) were evaluated as
      primary outcomes. Pain, as measured by the Brief Pain Inventory (BPI), self
      reported Patient Specific Functional Scale (PSFS), and Functional Assessment of
      Cancer Therapy-Breast (FACT-B) were secondary outcomes. Paired t tests were used
      for analysis, and 90% provided data for assessment at the end of the
      intervention. Participants experienced significant improvement in balance, as
      measured by FR, and flexibility, as measured by SR. The PSFS improved from 4.55
      to 7.21, and HR-QOL measured by FACT-B also improved; both P < .05. The score for
      the Pain Severity subscale of the BPI reduced. No adverse events nor development
      or worsening of lymphedema was observed. In all, 80% of participants adhered to
      the home program. Preliminary data suggest that yoga may reduce pain and improve
      balance and flexibility in BCSs with AIAA. A randomized controlled trial is
      needed to establish the definitive efficacy of yoga for objective functional
      improvement in BCSs related to AIAA.

PMID- 21733989
TI  - National decision-making on adopting new vaccines: a systematic review.
AB  - In recent years numerous new vaccines have been developed, offering potential
      reductions in the morbidity and mortality caused by a range of diseases. This has
      led to increased interest in decision-making about the adoption of new vaccines
      into national immunization programmes. This paper aims to systematically review
      the literature on national decision-making around the adoption of new vaccines. A
      thematic framework was developed inductively through analysis of the vaccine
      adoption decision-making frameworks included in the review. This thematic
      framework was then applied to the remaining studies included in the review. In
      total, 85 articles were included in the review: 39 articles describing examples
      of vaccine adoption decision-making, 26 presenting vaccine decision-making
      frameworks, 21 empirical articles of decision-making relating to vaccine adoption
      and 19 theoretical essays. An analysis of vaccine adoption decision-making
      frameworks identified nine broad categories of criteria: the importance of the
      health problem; vaccine characteristics; immunization programme considerations;
      acceptability; accessibility, equity and ethics; financial/economic issues;
      impact; alternative interventions and the decision-making process. The quality of
      the empirical studies was varied. Although some of the issues included in the
      frameworks were similar to those considered in the studies, there were also some
      notable differences. On the whole, the frameworks were more comprehensive than
      the studies, including a greater range of criteria. The existing literature
      provides a good foundation for further research into vaccine adoption decision
      making. The current review, in pulling together what is already known and by
      identifying strengths, weaknesses and gaps in the existing evidence base, aims to
      encourage a more focused and rigorous approach to the topic in future. This could
      help to identify the most appropriate ways to develop vaccine adoption decision
      making, so as to improve decisions and, ultimately, health outcomes.

PMID- 21733990
TI  - Hydrogen peroxide production is not primarily increased in human myotubes
      established from type 2 diabetic subjects.
AB  - CONTEXT: Increased oxidative stress and mitochondrial dysfunction have been
      implicated in the development of insulin resistance in type 2 diabetes. To date,
      it is unknown whether increased mitochondrial reactive oxygen species (ROS)
      production in skeletal muscle from patients with type 2 diabetes is primarily
      increased or a secondary adaptation to environmental, lifestyle, and hormonal
      factors. OBJECTIVE: This study investigates whether ROS production is primarily
      increased in isolated diabetic myotubes. SETTING: Mitochondrial membrane
      potential, hydrogen peroxide (H(2)O(2)), superoxide, and mitochondrial mass were
      determined in human myotubes precultured under normophysiological conditions.
      Furthermore, the corresponding ATP synthesis was measured in isolated
      mitochondria. PATIENTS: Muscle biopsies were taken from 10 lean subjects, 10
      obese subjects, and 10 subjects with type 2 diabetes; satellite cells were
      isolated, cultured, and differentiated to myotubes. RESULTS: Mitochondrial mass,
      membrane potential/mitochondrial mass, and superoxide-production/mitochondrial
      mass were not different between groups. In contrast, H(2)O(2)
      production/mitochondrial mass and ATP production were significantly reduced in
      diabetic myotubes compared to lean controls (P < 0.05). The ATP/H(2)O(2) ratios
      were not significantly different between groups. CONCLUSIONS: Our result
      indicates that the ROS production is not primarily increased in diabetic myotubes
      but rather is reduced. Moreover, the comparable ATP/H(2)O(2) ratios indicate that
      the reduced ROS production in diabetic myotubes parallels the reduced ATP
      production because ROS production in diabetic myotubes must be considered to be
      in a proportion comparable to lean. Thus, the increased ROS production seen in
      skeletal muscle of type 2 diabetic patients is an adaptation to the in vivo
      conditions.

PMID- 21733991
TI  - The economics of improving medication adherence in osteoporosis: validation and
      application of a simulation model.
AB  - CONTEXT: Adherence to osteoporosis treatment is low. Although new therapies and
      behavioral interventions may improve medication adherence, questions are likely
      to arise regarding their cost-effectiveness. OBJECTIVE: Our objectives were to
      develop and validate a model to simulate the clinical outcomes and costs arising
      from various osteoporosis medication adherence patterns among women initiating
      bisphosphonate treatment and to estimate the cost-effectiveness of a hypothetical
      intervention to improve medication adherence. DESIGN: We constructed a computer
      simulation using estimates of fracture rates, bisphosphonate treatment effects,
      costs, and utilities for health states drawn from the published literature.
      Probabilities of transitioning on and off treatment were estimated from
      administrative claims data. SETTING AND PATIENTS: Patients were women initiating
      bisphosphonate therapy from the general community. INTERVENTION: We evaluated a
      hypothetical behavioral intervention to improve medication adherence. MAIN
      OUTCOME MEASURES: Changes in 10-yr fracture rates and incremental cost
      effectiveness ratios were evaluated. RESULTS: A hypothetical intervention with a
      one-time cost of $250 and reducing bisphosphonate discontinuation by 30% had an
      incremental cost-effectiveness ratio (ICER) of $29,571 per quality-adjusted life
      year in 65-yr-old women initiating bisphosphonates. Although the ICER depended on
      patient age, intervention effectiveness, and intervention cost, the ICERs were
      less than $50,000 per quality-adjusted life year for the majority of intervention
      cost and effectiveness scenarios evaluated. Results were sensitive to
      bisphosphonate cost and effectiveness and assumptions about the rate at which
      intervention and treatment effects decline over time. CONCLUSIONS: Our results
      suggests that behavioral interventions to improve osteoporosis medication
      adherence will likely have favorable ICERs if their efficacy can be sustained.

PMID- 21733992
TI  - Autocrine proliferative effects of hGH are maintained in primary cultures of
      human mammary carcinoma cells.
AB  - CONTEXT: Empirical evidence suggests that autocrine human GH (hGH) may possess a
      proliferative and oncogenic role in human mammary carcinoma. However, this
      concept is largely derived from studies using cultured human mammary carcinoma
      cell (HMCC) lines. OBJECTIVE: We investigated the expression and functionality of
      hGH and the hGH receptor in isolated cultures of primary HMCC. DESIGN: Epithelial
      cell adhesion molecule-positive primary HMCC were isolated from surgical biopsies
      of patients with mammary carcinoma and cultured in vitro. Expression of hGH and
      hGH receptor was determined by RT-PCR, immunofluorescence microscopy, and ELISA.
      The proliferative response of the cultured primary HMCC to hGH stimulation or hGH
      inhibition with a hGH antagonist was determined. RESULTS: One hundred percent of
      cultured primary HMCC expressed the hGH receptor, and 52% expressed hGH at the
      mRNA level. hGH-positive primary HMCC produced hGH protein within the cell and
      secreted hGH to the media. Both hGH-negative and hGH-positive HMCC responded to
      hGH stimulation with large increases in cell number. hGH-positive HMCC responded
      to inhibition of hGH by a hGH antagonist with a decrease in cell number, whereas
      hGH-negative HMCC did not. CONCLUSION: Primary HMCC proliferate in response to
      hGH, and the proliferation of hGH-positive HMCC is inhibited by hGH antagonism.
      Inhibition of hGH in patients with mammary carcinoma may therefore limit tumor
      growth.

PMID- 21733993
TI  - Genetically determined dosage of follicle-stimulating hormone (FSH) affects male
      reproductive parameters.
AB  - CONTEXT: The detailed role of FSH in contributing to male testicular function and
      fertility has been debated. We have previously identified the association between
      the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, -211 bp from the
      mRNA start) and significantly reduced male serum FSH. OBJECTIVE: In the current
      study, the T-allele carriers of the FSHB -211 G/T single nucleotide polymorphism
      represented a natural model for documenting downstream phenotypic consequences of
      insufficient FSH action. DESIGN AND SUBJECTS: We genotyped rs10835638 in the
      population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT
      carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu,
      Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing
      was performed using linear regression (additive, recessive models) adjusted by
      age, body mass index, smoking, and recruitment center. RESULTS: Serum hormones
      directly correlated with the T-allele dosage of rs10835638 included FSH (additive
      model, P = 1.11 * 10(-6); T-allele effect, -0.41 IU/liter), inhibin-B (P = 2.16 *
      10(-3); T-allele effect, -14.67 pg/ml), and total testosterone (P = 9.30 * 10(
      3); T-allele effect, -1.46 nmol/liter). Parameters altered only among TT
      homozygotes were reduced testicular volume (recessive model, P = 1.19 * 10(-4);
      TT genotype effect, -9.47 ml) and increased serum LH (P = 2.25 * 10(-2); TT
      genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative
      genotypes did not affect sperm motility and morphology, calculated free
      testosterone, serum SHBG, and estradiol concentrations. CONCLUSION: We showed for
      the first time that genetically determined low FSH may have wider downstream
      effects on the male reproductive system, including impaired testes development,
      altered testicular hormone levels (inhibin-B, total testosterone, LH), and
      affected male reproductive potential.

PMID- 21733994
TI  - Differential nongenetic impact of birth weight versus third-trimester growth
      velocity on glucose metabolism and magnetic resonance imaging abdominal obesity
      in young healthy twins.
AB  - CONTEXT: Low birth weight is associated with type 2 diabetes, which to some
      extent may be mediated via abdominal adiposity and insulin resistance. Fetal
      growth velocity is high during the third trimester, constituting a potential
      critical window for organ programming. Intra-pair differences among monozygotic
      twins are instrumental in determining nongenetic associations between early
      environment and adult metabolic phenotype. OBJECTIVE: Our objective was to
      investigate the relationship between size at birth and third-trimester growth
      velocity on adult body composition and glucose metabolism using intra-pair
      differences in young healthy twins. METHODS: Fifty-eight healthy twins (42
      monozygotic/16 dizygotic) aged 18-24 yr participated. Insulin sensitivity was
      assessed using hyperinsulinemic-euglycemic clamps. Whole-body fat was assessed by
      dual-energy x-ray absorptiometry scan, whereas abdominal visceral and sc fat (L1
      L4) were assessed by magnetic resonance imaging. Third-trimester growth velocity
      was determined by repeated ultrasound examinations. RESULTS: Size at birth was
      nongenetically inversely associated with adult visceral and sc fat accumulation
      but unrelated to adult insulin action. In contrast, fetal growth velocity during
      third trimester was not associated with adult visceral or sc fat accumulation.
      Interestingly, third-trimester growth was associated with insulin action in a
      paradoxical inverse manner. CONCLUSIONS: Abdominal adiposity including
      accumulation of both sc and visceral fat may constitute primary nongenetic
      factors associated with low birth weight and reduced fetal growth before the
      third trimester. Reduced fetal growth during vs. before the third trimester may
      define distinct adult trajectories of metabolic and anthropometric
      characteristics influencing risk of developing type 2 diabetes.

PMID- 21733995
TI  - Identification of genetic alterations of AXIN2 gene in adrenocortical tumors.
AB  - BACKGROUND: Mutations of the beta-catenin gene (CTNNB1), which lead to
      constitutive activation of Wnt signaling, have recently been described in
      adrenocortical adenomas (AA) and carcinomas (ACC). However, somatic CTNNB1
      mutations may explain only about 50% of beta-catenin accumulation observed in
      adrenocortical tumors, indicating that other components of the Wnt pathway may be
      involved. OBJECTIVE: The objective of the study was to investigate whether
      alterations in AXIN2 may be present in adrenocortical tumors. METHODS: We studied
      49 human adrenocortical samples: 30 AA, six ACC, five primary pigmented nodular
      adrenocortical disease five ACTH-independent macronodular adrenal hyperplasias
      (AIMAH), and three ACTH-dependent hyperplasias in addition to the human ACC cell
      lines SW13 and H295R. Samples were screened for somatic genetic alterations in
      exon 3 of CTNNB1 and exons 5, 7, and 9 of AXIN2. RESULTS: We found an in-frame,
      12-bp deletion beginning at coding nucleotide 2013 in exon 7 of the AXIN2 gene,
      c.2013_2024del12 (p.Arg671_Pro674del), in two of 30 AA (7%), one of six ACC
      (17%), and the ACC H295R cell line. Immunohistochemistry revealed that tumors
      with AXIN2 genetic defects showed nuclear/cytoplasmic accumulation of beta
      catenin, indicating the activation of Wnt signaling. In addition, the ACC and
      H295R cells with AXIN2 deletion (c.2013_2024del12) harbored p.Ser45del and
      p.Ser45Pro CTNNB1 mutations, respectively. Two single-nucleotide polymorphisms
      were identified in exon 7 of AXIN2, c.2351C>T in 2 AA, and one AIMAH and
      c.2342A>G in an AIMAH tissue. CONCLUSION: The present study reports, for the
      first time, that AXIN2 genetic defects may be found in adrenocortical tumors.
      However, the functional consequence of this genetic alteration remains to be
      determined.

PMID- 21733996
TI  - The protein kinase a pathway regulates CYP17 expression and androgen production
      in the human placenta.
AB  - BACKGROUND: Our previous work demonstrated that the human placenta expresses
      CYP17 and is capable of de novo production of C-19 steroids; thus, it has
      intrinsic capacity to generate estrogens without fetal or maternal steroid
      precursors. OBJECTIVE: Our objective was to elucidate the regulation of CYP17
      expression and androgen production in the human trophoblasts. METHODS: Fresh
      placentas and JEG-3 cells were used for all experiments. CYP17 mRNA analysis was
      performed via RT-PCR, and steroid products were quantified using RIA. To assess
      protein kinase A (PKA) pathway involvement, a pharmacological approach was used
      with forskolin (FSK) (10 MUM), an activator, and H89 (10 MUM), an inhibitor of
      the PKA pathway. RESULTS: FSK treatment amplified CYP17 mRNA levels in both cell
      types when compared with basal, with levels increasing over time, peaking at 72
      h, and appearing more robust in primary cells; this difference ranged from 2- to
      10-fold and was statistically significant at all time points. Meanwhile, H89
      reduced CYP17 levels and blunted the effect of FSK when the treatments were
      combined. Similarly, FSK treatment significantly increased 17alpha
      hydroxyprogesterone concentration in both cell cultures, and H89 blunted that
      effect as well. CONCLUSIONS: We confirm again that the human trophoblast
      expresses CYP17 and is able to generate estrogen precursors. We demonstrate that
      this process is regulated, at least in part, by the cAMP/PKA pathway.

PMID- 21733997
TI  - Deletions of the androgen-metabolizing UGT2B genes have an effect on circulating
      steroid levels and biochemical recurrence after radical prostatectomy in
      localized prostate cancer.
AB  - CONTEXT: The prognostic relevance of inherited variations in hormone-related
      genes in the context of prostate cancer (PCa) progression has not been well
      studied. Of these, UDP-glucuronosyltransferase (UGT) gene products lead to
      inactivation of steroids. OBJECTIVE: Our objective was to determine whether
      polymorphisms in five UGT genes, involved in steroid metabolism, are associated
      with the risk of biochemical recurrence after radical prostatectomy (RP) and to
      examine their relationship with hormonal exposure. DESIGN: The study included 526
      Caucasian and 320 Asian men who underwent RP for clinically localized PCa. The
      relationship between genotypes and biochemical recurrence were assessed with
      multivariate Cox proportional hazard models. Plasma steroids were measured using
      specific and sensitive mass spectrometry-based methods. RESULTS: The presence of
      at least two deleted copies of UGT2B17 and UGT2B28 genes resulted in a hazard
      ratio of 2.26 (95% confidence interval = 1.41-3.61; P = 0.0007) for Caucasians
      and 2.16 (95% confidence interval = 1.24-3.73; P = 0.006) for Asians. A positive
      association was observed only between UGT2B17 deletion and the Gleason score in
      Asians, whereas no other interaction was shown with prostate-specific antigen,
      Gleason score, and TNM (tumor node metastasis) staging. Patients carrying UGT2B17
      deletions and those with three deleted UGT2B copies had significantly lower
      androgen glucuronides, in support of an altered androgen metabolism. CONCLUSION:
      This study is the first to recognize the prognostic significance of common
      deletions in steroid inactivation pathways in localized PCa after RP. Alteration
      of circulating steroid levels associated with UGT2B gene deletions further
      support the notion that such inherited genomic deletions have the potential to
      modify hormonal exposure and risk of recurrence.

PMID- 21733998
TI  - The Hormone Foundation's: Patient guide to vitamin D deficiency.

PMID- 21734001
TI  - Approach to the child with fractures.
AB  - Evaluation of the child with fractures is challenging, as no clear guidelines
      exist to distinguish traumatic from pathological fractures. Although most
      fractures in childhood are benign, recurrent fractures may be associated with a
      wide variety of primary skeletal diseases as well as secondary causes,
      necessitating a careful history and physical exam to guide the evaluation. There
      is no "gold standard" for the evaluation and treatment of children with fractures
      and low bone mineral density (BMD); therefore, the diagnosis of osteoporosis in a
      pediatric patient should be made using a combination of clinical and radiographic
      features. Interpretation of bone densitometry in growing patients presents a
      unique set of challenges because areal BMD measured by dual-energy x-ray
      absorptiometry depends on multiple dynamic variables. Interpretation of pediatric
      dual-energy x-ray absorptiometry should be based on Z-scores (sd scores compared
      to age, sex, and ethnicity-matched controls), using normative databases specific
      to the brand of densitometer and the patient population. Given the skeleton's
      ability to recover from low BMD through modeling and remodeling, optimizing
      management of underlying conditions leading to bone fragility is the initial
      step. Conservative measures including calcium and vitamin D supplementation and
      weight-bearing physical activity are important interventions that should not be
      overlooked. The use of bisphosphonates in children and adolescents is
      controversial due to lack of long-term efficacy and safety data and should be
      limited to clinical trials and compassionate therapy in children with
      significantly compromised quality of life. Close monitoring is required, and
      further study is necessary to assess their long-term safety and efficacy in
      children.

PMID- 21734002
TI  - Double pituitary and conserved function in an adult patient with
      neurofibromatosis type 1.

PMID- 21734003
TI  - The safety of incretin-based therapies--review of the scientific evidence.
AB  - CONTEXT: Antidiabetic therapies based on potentiation of incretin action are now
      widely used; however, understanding of their long-term safety remains incomplete.
      EVIDENCE ACQUISITION: We searched articles in PubMed for data assessing the
      safety of incretin-based therapies. EVIDENCE SYNTHESIS: Three major areas of
      interest are reviewed: incretin action in the cardiovascular system,
      pancreatitis, and cancer. Incretin therapies reduce weight gain, minimize
      hypoglycemia, decrease inflammation, and are cardioprotective in preclinical
      studies. However, data permitting conclusions about whether incretin therapies
      modify the development of cardiovascular events in humans are not available. Case
      reports link incretin therapies to pancreatitis, but retrospective case control
      studies do not associate pancreatitis with glucagon-like peptide-1 receptor (GLP
      1R) agonists or dipeptidyl peptidase-4 inhibitors. Preclinical studies of
      pancreatitis have yielded conflicting results, and mechanisms linking incretin
      receptor activation to pancreatic inflammation have not yet been forthcoming. GLP
      1R activation promotes C-cell hyperplasia and medullary thyroid cancer in
      rodents; however, long-term clinical studies of sufficient size and duration to
      permit conclusions regarding cancer and incretin therapeutics have not yet been
      completed. CONCLUSIONS: The available data on incretin action and incidence of
      cardiovascular events, pancreatitis, or cancer are not yet sufficient or robust
      enough to permit firm conclusions regarding associations with incretin-based
      therapies in humans with diabetes. The forthcoming results of long-term
      cardiovascular safety studies should provide more conclusive information about
      the safety of GLP-1R agonists and dipeptidyl peptidase-4 inhibitors in diabetic
      patients.

PMID- 21734004
TI  - Hepatic VLDL overproduction: is hyperinsulinemia or insulin resistance the
      culprit?

PMID- 21734005
TI  - The nutrient problem, as seen through the lens of calcium.

PMID- 21734006
TI  - Management of recurrent/persistent papillary thyroid carcinoma: efficacy of the
      surgical option.

PMID- 21734011
TI  - Genetic analysis in the Collaborative Cross breeding population.
AB  - Genetic reference populations in model organisms are critical resources for
      systems genetic analysis of disease related phenotypes. The breeding history of
      these inbred panels may influence detectable allelic and phenotypic diversity.
      The existing panel of common inbred strains reflects historical selection biases,
      and existing recombinant inbred panels have low allelic diversity. All such
      populations may be subject to consequences of inbreeding depression. The
      Collaborative Cross (CC) is a mouse reference population with high allelic
      diversity that is being constructed using a randomized breeding design that
      systematically outcrosses eight founder strains, followed by inbreeding to obtain
      new recombinant inbred strains. Five of the eight founders are common laboratory
      strains, and three are wild-derived. Since its inception, the partially inbred CC
      has been characterized for physiological, morphological, and behavioral traits.
      The construction of this population provided a unique opportunity to observe
      phenotypic variation as new allelic combinations arose through intercrossing and
      inbreeding to create new stable genetic combinations. Processes including
      inbreeding depression and its impact on allelic and phenotypic diversity were
      assessed. Phenotypic variation in the CC breeding population exceeds that of
      existing mouse genetic reference populations due to both high founder genetic
      diversity and novel epistatic combinations. However, some focal evidence of
      allele purging was detected including a suggestive QTL for litter size in a
      location of changing allele frequency. Despite these inescapable pressures, high
      diversity and precision for genetic mapping remain. These results demonstrate the
      potential of the CC population once completed and highlight implications for
      development of related populations.

PMID- 21734012
TI  - Expansion of cyclin D and CDK1 paralogs in Oikopleura dioica, a chordate
      employing diverse cell cycle variants.
AB  - Proliferative and endoreduplicative cell cycles are used to variable extents
      during the ontogeny of individual organisms and in different evolutionary
      lineages. Chordate growth and development is typically dominated by proliferative
      cycles, but the urochordate, Oikopleura dioica, has systemically elaborated a
      number of endocycling modes to support rapid development and growth in an
      extraordinarily short chordate life cycle. Here, we identify the O. dioica cyclin
      and cyclin-dependent kinase (CDK) complements and assess their deployment with
      respect to mitotic, meiotic, and endoreduplicative life cycle phases. Oikopleura
      dioica's "transcriptional" cyclin and CDK complements are similar to other
      complex invertebrates, whereas both the "cell cycle" cyclin and CDK complements
      display astonishing amplifications centered on the cyclin D, cyclin B, and CDK1
      families. Somatic endocycles in O. dioica involve downregulation of cyclins B and
      A, as in other endocycle model systems, but are also characterized by overlapping
      expression of an array of cyclin D isoforms. Amplification of the mitotic CDK1
      family to five paralogs, which continue to be expressed in endocycling phases, is
      unexpected as suppression of CDK1 activity is central to endocycle transitions in
      Drosophila and mammals. This amplification is unique among metazoans, and
      substitutions in odCDK1 paralogs in the nearly invariant cyclin interaction
      PSTAIRE helix show striking parallels to those in the only other known eukaryotic
      CDK1 paralogs, plant CDKA and CDKB. As plant CDK1 paralogs exhibit an expanded
      repertoire of cyclin partners, including cyclin D, the evolutionary coexpansion
      of odCDK1 and odCyclin D families suggests that multiple CDK1-cyclin D complexes
      may modulate spatiotemporal control of kinase activity and substrate specificity
      in diverse cell cycle variants.

PMID- 21734013
TI  - Genome-wide profiling of chromatin signatures reveals epigenetic regulation of
      MicroRNA genes in colorectal cancer.
AB  - Altered expression of microRNAs (miRNA) occurs commonly in human cancer, but the
      mechanisms are generally poorly understood. In this study, we examined the
      contribution of epigenetic mechanisms to miRNA dysregulation in colorectal cancer
      by carrying out high-resolution ChIP-seq. Specifically, we conducted genome-wide
      profiling of trimethylated histone H3 lysine 4 (H3K4me3), trimethylated histone
      H3 lysine 27 (H3K27me3), and dimethylated histone H3 lysine 79 (H3K79me2) in
      colorectal cancer cell lines. Combining miRNA expression profiles with chromatin
      signatures enabled us to predict the active promoters of 233 miRNAs encoded in
      174 putative primary transcription units. By then comparing miRNA expression and
      histone modification before and after DNA demethylation, we identified 47 miRNAs
      encoded in 37 primary transcription units as potential targets of epigenetic
      silencing. The promoters of 22 transcription units were associated with CpG
      islands (CGI), all of which were hypermethylated in colorectal cancer cells. DNA
      demethylation led to increased H3K4me3 marking at silenced miRNA genes, whereas
      no restoration of H3K79me2 was detected in CGI-methylated miRNA genes. DNA
      demethylation also led to upregulation of H3K4me3 and H3K27me3 in a number of CGI
      methylated miRNA genes. Among the miRNAs we found to be dysregulated, many of
      which are implicated in human cancer, miR-1-1 was methylated frequently in early
      and advanced colorectal cancer in which it may act as a tumor suppressor. Our
      findings offer insight into the association between chromatin signatures and
      miRNA dysregulation in cancer, and they also suggest that miRNA reexpression may
      contribute to the effects of epigenetic therapy.

PMID- 21734014
TI  - CXCR3 enhances a T-cell-dependent epidermal proliferative response and promotes
      skin tumorigenesis.
AB  - The chemokine receptor CXCR3 has been proposed to play a critical role in host
      antitumor responses. In this study, we defined CXCR3-expressing immune cell
      infiltration in human skin squamous cell carcinomas and then used CXCR3-deficient
      mice to assess the contribution of CXCR3 to skin tumorigenesis. Our studies
      employed two established protocols for chemical skin carcinogenesis
      [methylcholanthrene (MCA) or 7,12-dimethylbenz(a)anthracene (DMBA)/12-O
      tetradecanoylphorbol-13-acetate (TPA) models]. CXCR3 deletion did not affect
      tumor development in the MCA model; however, CXCR3 was important in the DMBA/TPA
      model where gene deletion reduced the incidence of skin tumors. This decreased
      incidence of skin tumors did not reflect differences in epidermal development but
      rather was associated with reduced epidermal thickness and proliferation in
      CXCR3(-/-) mice, implicating the CXCR3 pathway in DMBA/TPA-induced epidermal
      inflammation and proliferation. Notably, CXCR3 expressed in CD4(+) and CD8(+) T
      cells was found to be important for enhanced epidermal proliferation.
      Specifically, CXCR3-deficient mice reconstituted with T cells isolated from wild
      type mice treated with DMBA/TPA restored wild-type levels of epidermal
      proliferation in the mutant mice. Taken together, our findings establish that
      CXCR3 promotes epidermal tumorigenesis likely through a T-cell-dependent
      induction of keratinocyte proliferation.

PMID- 21734015
TI  - Dual function of ERRalpha in breast cancer and bone metastasis formation:
      implication of VEGF and osteoprotegerin.
AB  - Bone metastasis is a complication occurring in up to 70% of advanced breast
      cancer patients. The estrogen receptor-related receptor alpha (ERRalpha) has been
      implicated in breast cancer and bone development, prompting us to examine whether
      ERRalpha may function in promoting the osteolytic growth of breast cancer cells
      in bone. In a mouse xenograft model of metastatic human breast cancer,
      overexpression of wild-type ERRalpha reduced metastasis, whereas overexpression
      of a dominant negative mutant promoted metastasis. Osteoclasts were directly
      affected and ERRalpha upregulated the osteoclastogenesis inhibitor,
      osteoprotegerin (OPG), providing a direct mechanistic basis for understanding how
      ERRalpha reduced breast cancer cell growth in bone. In contrast, ERRalpha
      overexpression increased breast cancer cell growth in the mammary gland. ERRalpha
      overexpressing primary tumors were highly vascularized, consistent with an
      observed upregulation of angiogenic growth factor, the VEGF. In support of these
      findings, we documented that elevated expression of ERRalpha mRNA in breast
      carcinomas was associated with high expression of OPG and VEGF and with disease
      progression. In conclusion, our results show that ERRalpha plays a dual role in
      breast cancer progression in promoting the local growth of tumor cells, but
      decreasing metastatic growth of osteolytic lesions in bone.

PMID- 21734016
TI  - Islet amyloid polypeptide is a target antigen for diabetogenic CD4+ T cells.
AB  - OBJECTIVE: To investigate autoantigens in beta-cells, we have used a panel of
      pathogenic T-cell clones that were derived from the NOD mouse. Our particular
      focus in this study was on the identification of the target antigen for the
      highly diabetogenic T-cell clone BDC-5.2.9. RESEARCH DESIGN AND METHODS: To
      purify beta-cell antigens, we applied sequential size exclusion chromatography
      and reverse-phase high-performance liquid chromatography to membrane preparations
      of beta-cell tumors. The presence of antigen was monitored by measuring the
      interferon-gamma production of BDC-5.2.9 in response to chromatographic fractions
      in the presence of NOD antigen-presenting cells. Peak antigenic fractions were
      analyzed by ion-trap mass spectrometry, and candidate proteins were further
      investigated through peptide analysis and, where possible, testing of islet
      tissue from gene knockout mice. RESULTS: Mass-spectrometric analysis revealed the
      presence of islet amyloid polypeptide (IAPP) in antigen-containing fractions.
      Confirmation of IAPP as the antigen target was demonstrated by the inability of
      islets from IAPP-deficient mice to stimulate BDC-5.2.9 in vitro and in vivo and
      by the existence of an IAPP-derived peptide that strongly stimulates BCD-5.2.9.
      CONCLUSIONS: IAPP is the target antigen for the diabetogenic CD4 T-cell clone BDC
      5.2.9.

PMID- 21734017
TI  - High-fat diet-induced adipocyte cell death occurs through a cyclophilin D
      intrinsic signaling pathway independent of adipose tissue inflammation.
AB  - OBJECTIVE: Previous studies have demonstrated that mice fed a high-fat diet (HFD)
      develop insulin resistance with proinflammatory macrophage infiltration into
      white adipose tissue. Concomitantly, adipocytes undergo programmed cell death
      with the loss of the adipocyte-specific lipid droplet protein perilipin, and the
      dead/dying adipocytes are surrounded by macrophages that are organized into crown
      like structures. This study investigated whether adipocyte cell death provides
      the driving signal for macrophage inflammation or if inflammation induces
      adipocyte cell death. RESEARCH DESIGN AND METHODS: Two knockout mouse models were
      used: granulocyte/monocyte-colony stimulating factor (GM-CSF)-null mice that are
      protected against HFD-induced adipose tissue inflammation and cyclophilin D (CyP
      D)-null mice that are protected against adipocyte cell death. Mice were fed for 4
      14 weeks with a 60% HFD, and different markers of cell death and inflammation
      were analyzed. RESULTS: HFD induced a normal extent of adipocyte cell death in GM
      CSF-null mice, despite a marked reduction in adipose tissue inflammation.
      Similarly, depletion of macrophages by clodronate treatment prevented HFD-induced
      adipose tissue inflammation without any affect on adipocyte cell death. However,
      CyP-D deficiency strongly protected adipocytes from HFD-induced cell death,
      without affecting adipose tissue inflammation. CONCLUSIONS: These data
      demonstrate that HFD-induced adipocyte cell death is an intrinsic cellular
      response that is CyP-D dependent but is independent of macrophage
      infiltration/activation.

PMID- 21734018
TI  - Rhythmic activity of neurons in the rostral ventrolateral medulla of conscious
      cats: effect of removal of vestibular inputs.
AB  - Although it is well established that bulbospinal neurons located in the rostral
      ventrolateral medulla (RVLM) play a pivotal role in regulating sympathetic nerve
      activity and blood pressure, virtually all neurophysiological studies of this
      region have been conducted in anesthetized or decerebrate animals. In the present
      study, we used time- and frequency-domain analyses to characterize the naturally
      occurring discharges of RVLM neurons in conscious cats. Specifically, we compared
      their activity to fluctuations in carotid artery blood flow to identify neurons
      with cardiac-related (CR) activity; we then considered whether neurons with CR
      activity also had a higher-frequency rhythmic firing pattern. In addition, we
      ascertained whether the surgical removal of vestibular inputs altered the
      rhythmic discharge properties of RVLM neurons. Less than 10% of RVLM neurons
      expressed CR activity, although the likelihood of observing a neuron with CR
      activity in the RVLM varied between recording sessions, even when tracking
      occurred in a very limited area and was higher after vestibular inputs were
      surgically removed. Either a 10-Hz or a 20- to 30-Hz rhythmic discharge pattern
      coexisted with the CR discharges in some of the RVLM neurons. Additionally, the
      firing rate of RVLM neurons, including those with CR activity, decreased after
      vestibular lesions. These findings raise the prospect that RVLM neurons may or
      may not express rhythmic firing patterns at a particular time due to a variety of
      influences, including descending projections from higher brain centers and
      sensory inputs, such as those from the vestibular system.

PMID- 21734019
TI  - Gastric bypass reduces fat intake and preference.
AB  - Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This
      study investigated how gastric bypass affects intake of and preference for high
      fat food in an experimental (rat) study and within a trial setting (human).
      Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr
      after surgery compared with patients after vertical-banded gastroplasty (P =
      0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and
      increased standard low-fat chow consumption compared with sham controls (P <
      0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed
      much lower preferences for Intralipid concentrations > 0.5% in an ascending
      concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle
      preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after
      surgery. However, there was no difference in appetitive or consummatory behavior
      in the brief access test between the two groups (P = 0.71) using similar
      Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1
      (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml
      corn oil after saccharin ingestion in gastric bypass rats induced a conditioned
      taste aversion. These findings suggest that changes in fat preference may
      contribute to long-term maintained weight loss after gastric bypass.
      Postingestive effects of high-fat nutrients resulting in conditioned taste
      aversion may partially explain this observation; the role of GLP-1 in mediating
      postprandial responses after gastric bypass requires further investigation.

PMID- 21734020
TI  - Anatomical dissociation of melanocortin receptor agonist effects on taste- and
      gut-sensitive feeding processes.
AB  - Injections of the melanocortin 3/4 receptor (MCR) agonist melanotan II (MTII) to
      a variety of brain structures produces anorexia, suggesting distributed brain MCR
      control of food intake. We performed a detailed analysis of feeding behavior
      (licking microstructure analysis) after a range of MTII doses (0.005 nM to 1 nM)
      was targeted to the forebrain (third ventricle, 3V) or hindbrain (fourth
      ventricle, 4V) regions. MTII (0.1 nM and 1 nM) delivered to the 3V or 4V
      significantly reduced 0.8 M sucrose intake. The anorexia was mediated by
      reductions in the number of licking bursts in the meal, intrameal ingestion rate,
      and meal duration; these measures have been associated with postingestive
      feedback inhibition of feeding. Anorexia after 3V but not 4V MTII injection was
      also associated with a reduced rate of licking in the first minute (initial lick
      rate) and reduced mean duration of licking bursts; these measures have been
      associated with taste evaluation. MTII effects on taste evaluation were further
      explored: In experiment 2, 3V MTII (1 nM) significantly reduced intake of
      noncaloric 4 mM saccharin and 0.1 M and 1 M sucrose solutions, but not water. The
      anorexia was again associated with reduced number of licking bursts, ingestion
      rate, meal duration, initial lick rate, and mean burst duration. In experiments 3
      and 4, brief access (20 s) licking responses for sweet sucrose (0.015 M to 0.25
      M) and bitter quinine hydrochloride (0.01 mM to 1 mM) solutions were evaluated.
      Licking responses for sucrose were suppressed, whereas those for quinine
      solutions were increased after 3V MTII, but not after 4V MTII injections (0.1 nM
      and 1 nM). The results suggest that multiple brain MCR sites influence
      sensitivity to visceral feedback, whereas forebrain MCR stimulation is necessary
      to influence taste responsiveness, possibly through attenuation of the perceived
      intensity of taste stimuli.

PMID- 21734021
TI  - Identification and validation of differentially expressed transcripts in a
      hepatocyte model of cold-induced glycerol production in rainbow smelt (Osmerus
      mordax).
AB  - Rainbow smelt (Osmerus mordax) avoid freezing by producing antifreeze protein
      (AFP) and accumulating glycerol. Glyceroneogenesis occurs in liver via a branch
      in glycolysis and gluconeogenesis and is activated by low temperature.
      Hepatocytes were isolated from the livers of fish acclimated to 8 degrees C.
      Cells were incubated at warm (8 degrees C; nonglycerol accumulating) or cold (0.4
      degrees C; glycerol accumulating) temperature over a 72-h time course. Reciprocal
      suppression subtractive hybridization libraries enriched for cold-responsive
      transcripts were constructed at 72 h. Microarray analyses using a 16K salmonid
      cDNA array were performed at 24, 48, and 72 h. Expression of type II AFP and 21
      carbohydrate, amino acid, or lipid metabolism-related transcripts were validated
      using quantitative RT-PCR. Type II AFP transcript levels were not directly
      temperature related. In cold cells, levels of the glucose synthesis transcript
      were transiently higher. Increased glycerol production was not associated with
      increased phosphofructokinase or cytosolic glycerol-3-phosphate dehydrogenase
      transcript levels. Levels of transcripts (phosphoenolpyruvate carboxykinase,
      mitochondrial malate dehydrogenase, alanine aminotransferase, glutamate
      dehydrogenase, and aquaglyceroporin 9) associated with mobilization of amino
      acids to fuel glycerol accumulation were all transiently higher, suggesting a
      common regulatory mechanism. In cold compared with warm cells, pyruvate
      dehydrogenase kinase [an inhibitor of pyruvate dehydrogenase (PDH)] transcript
      levels were 20-fold higher. Potent inhibition of PDH would direct pyruvate and
      oxaloacetate derived from amino acids to glycerol, as opposed to oxidation via
      the citric acid cycle. Levels of a transcript potentially encoding glycerol-3
      phosphatase, an enzyme not yet characterized in any vertebrate species, were
      higher following cold incubation. Finally, this study also presents the novel
      finding of increased glutamine synthetase transcript levels in response to low
      temperature.

PMID- 21734022
TI  - Changes in cerebral blood flow velocity in patients with hypothyroidism.
AB  - BACKGROUND: At present, hypothyroidism is a well-known risk factor for
      cardiovascular disorders. The aim of this study was to assess the effects of
      hypothyroidism on cerebral blood flow velocity with transcranial Doppler (TCD)
      ultrasonography. DESIGN AND METHODS: In this study, 30 subjects were enrolled for
      clinical, subclinical, and healthy control groups. Bilateral middle cerebral
      artery (MCA) peak-systolic, end-diastolic, and mean blood flow velocities;
      Gosling's pulsatility index values; and Pourcelot's resistance index values were
      recorded and compared with each other. TCD was performed in clinical hypothyroid
      patients after they became euthyroid with thyroid hormone replacement therapy
      (HRT). The initial and post-HRT results for the clinical hypothyroid group were
      then compared and evaluated. RESULTS: There were 30 subjects in each group.
      Men/women ratio and mean age in clinical hypothyroid, subclinical hypothyroid,
      and control groups were 3/27, 4/26, and 5/25, and 37.4, 34.4, and 36.7
      respectively. Peak-systolic, end-diastolic, and mean blood flow velocities of
      bilateral MCA were similar in clinical and subclinical hypothyroid groups but
      significantly higher when compared with the control group. After adequate thyroid
      HRT in clinical hypothyroid group, the peak-systolic, end-diastolic, and mean
      blood flow velocities were significantly decreased. CONCLUSIONS: Increased
      cerebral blood flow velocities were observed in clinical and subclinical patients
      with hypothyroidism. The normalization of increased blood flow velocity with
      thyroid HRT suggests a reversible condition.

PMID- 21734023
TI  - Improved performance of bacterium and yeast identification by a commercial matrix
      assisted laser desorption ionization-time of flight mass spectrometry system in
      the clinical microbiology laboratory.

PMID- 21734024
TI  - Acute hepatitis as a manifestation of parvovirus B19 infection.
AB  - There are few reports in the literature of hepatitis as a manifestation of
      parvovirus B19 infection. We describe a case of parvovirus B19-associated acute
      hepatitis diagnosed based on a positive serologic test (IgM) and molecular
      detection of parvovirus B19 DNA in a liver biopsy specimen. Parvovirus B19
      infection should be considered in the differential diagnosis of patients
      presenting with acute hepatitis.

PMID- 21734025
TI  - KPC screening by updated BD Phoenix and Vitek 2 automated systems.
AB  - Current BD Phoenix and Vitek 2 methodologies were assessed as screens for KPC
      beta-lactamases. Using carbapenem MICs or expert system interpretations as
      screens, both systems exhibited high (97%) sensitivity in tests with 103 well
      characterized Gram-negative isolates, 77 of which were KPC producers.

PMID- 21734026
TI  - Hallucinations, sensory neuropathy, and peripheral visual deficits in a young
      woman infected with Bartonella koehlerae.
AB  - A young woman experiencing depression, anxiety, mood swings, severe headaches,
      muscle spasms, interphalangeal joint stiffness, decreased peripheral vision,
      diminished tactile sensation, and hallucinations was persistently Bartonella
      koehlerae seroreactive and bacteremic. Following antibiotic treatment, B.
      koehlerae antibodies and DNA were not detected and all symptoms resolved.

PMID- 21734027
TI  - Helicobacter pylori homB, but not cagA, is associated with gastric cancer in
      Iran.
AB  - While several distinct virulence factors of Helicobacter pylori have been shown
      to be associated with different clinical outcomes, there is still much to learn
      about the role of different bacterial factors in gastric carcinogenesis. This
      study looked at the distribution of the cagA, homA, and homB genes in strains
      isolated from patients suffering from gastroduodenal diseases in Iran and
      assessed if there was any association between disease state and the presence of
      the aforementioned virulence factors. Genomic DNA from 138 H. pylori strains was
      isolated and genotyped via PCR. Strains were obtained from dyspeptic patients (35
      from gastritis patients, 62 from peptic ulcer patients, and 41 from gastric
      cancer patients) at the Teaching Touba Clinic and Imam Hospital of the Mazandaran
      University of Medical Sciences in Sari, Iran. The overall prevalence rates of
      cagA, homA, and homB were 58%, 54%, and 43%, respectively. Stratification of
      patients showed a significant difference in the prevalence of H. pylori virulence
      genes across the disease states. The frequency of homB was statistically
      significantly higher in gastric cancer patients (78%) than in patients suffering
      from peptic ulcers (20%) or gastritis (43%) (P < 0.0001). The presence of homB
      was also associated with the presence of cagA (r = 0.243). These data suggest
      that in this population the presence of homB may be a predictor of more virulent
      strains of H. pylori and influence the severity of disease manifestation.

PMID- 21734028
TI  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      based single nucleotide polymorphism genotyping assay using iPLEX gold technology
      for identification of Mycobacterium tuberculosis complex species and lineages.
AB  - The major goal of the present study was to investigate the potential use of a
      novel single nucleotide polymorphism (SNP) genotyping technology, called iPLEX
      Gold (Sequenom), for the simultaneous analysis of 16 SNPs that have been
      previously validated as useful for identification of Mycobacterium tuberculosis
      complex (MTBC) species and classification of MTBC isolates into distinct genetic
      lineages, known as principal genetic groups (PGGs) and SNP cluster groups (SCGs).
      In this context, we developed a 16-plex iPLEX assay based on an allele-specific
      primer single-base-extension reaction using the iPLEX Gold kit (Sequenom),
      followed by matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS) analysis on the commercially available Sequenom
      MassARRAY platform. This assay was tested on a panel of 55 well-characterized
      MTBC strains that were also genotyped for the same loci using the previously
      reported SNaPshot assay, as well as 10 non-MTBC mycobacteria and 4 bacteria not
      belonging to the genus Mycobacterium. All MTBC samples were successfully analyzed
      with the iPLEX assay, which yielded clear allelic data for 99.9% of the SNPs (879
      out of 880). No false-positive results were obtained with the negative controls.
      Compared to the SNaPshot assay, the newly developed 16-plex iPLEX assay produced
      fully concordant results that allowed reliable differentiation of MTBC species
      and recognition of lineages, thus demonstrating its potential value in
      diagnostic, epidemiological, and evolutionary applications. Compared to the
      SNaPshot approach, the implementation of the iPLEX technology could offer a
      higher throughput and could be a more flexible and cost-effective option for
      microbiology laboratories.

PMID- 21734030
TI  - Real-time detection of blaKPC in clinical samples and surveillance specimens.
AB  - A real-time PCR assay was developed targeting the bla(KPC) responsible for
      Klebsiella pneumoniae carbapenemase (KPC)-mediated carbapenem resistance and was
      validated for testing colonies or enrichment broth cultures. The assay accurately
      detects KPC-containing strains with high analytical specificity and sensitivity.

PMID- 21734029
TI  - High concordance between the position-specific scoring matrix and geno2pheno
      algorithms for genotypic interpretation of HIV-1 tropism: V3 length as the major
      cause of disagreement.
AB  - The agreement between the position-specific scoring matrix (PSSM) and geno2pheno
      as tools for genotypic interpretation of HIV-1 tropism using 800 clinical
      specimens was assessed. There was an overall concordance of 88%. Disagreement was
      found mostly in specimens with short V3 lengths (<35 amino acids). Thus,
      consideration of V3 lengths should improve the predictability of HIV-1 tropism
      using genotypic algorithms.

PMID- 21734031
TI  - Multiplex method for simultaneous serological detection of porcine reproductive
      and respiratory syndrome virus and porcine circovirus type 2.
AB  - Porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory
      syndrome virus (PRRSV) are major contributors to the porcine respiratory disease
      complex (PRDC). Routine serological diagnosis and surveillance play an important
      role in the prevention of PRDC, as it is a leading cause of economic losses to
      the swine industry. We herein describe an advanced microsphere-based immunoassay
      that permits the simultaneous detection of antibodies to PCV2 and PRRSV, thereby
      reducing the time and effort involved in testing. Recombinant PRRSV nucleoprotein
      antigen and the PCV2 capsid antigen were coupled to fluorophore-dyed beads with
      distinct spectral addresses. Weekly serum samples from 72 pigs that were
      experimentally exposed to either PCV2, PRRSV, or both PCV2 and PRRSV were used to
      validate the microbead assay (MBA) in comparison with the "gold standard" enzyme
      linked immunosorbent assays. The kinetics of the PCV2- and PRRSV-specific
      antibody responses measured by the microbead assay were comparable to those of
      the standard assays; Spearman's rank correlations were 0.72 (P < 0.001) for PRRSV
      and 0.80 (P < 0.001) for PCV2. Diagnostic sensitivity and specificity were
      determined using field sera whose positive or negative status was determined by
      the standard tests. The diagnostic sensitivity and specificity were both 98% for
      PCV2 and were 91% and 93%, respectively, for PRRSV (kappa coefficients, 0.85 and
      0.67 for PCV2 and PRRSV, respectively). Multiplexing did not interfere with assay
      performance or diagnostic sensitivity. Therefore, the described study
      demonstrates proof of concept for the development of more versatile and
      economical microbead array-based multiplex serological test panels for veterinary
      use.

PMID- 21734032
TI  - Infections caused by unusual Methylobacterium species.
AB  - We describe six patients with hospital-acquired bacteremia caused by
      Methylobacterium species, including M. radiotolerans (n = 2), M. thiocyanatum (n
      = 2), M. aminovorans (n = 1), and M. lusitanum (n = 1), which were confirmed to
      species level by 16S rRNA gene sequence analysis. Among these patients, five had
      catheter-related bacteremia and all had favorable outcomes.

PMID- 21734033
TI  - Effect of the expression of aquaporins 1 and 3 in mouse oocytes and compacted
      eight-cell embryos on the nucleation temperature for intracellular ice formation.
AB  - The occurrence of intracellular ice formation (IIF) is the most important factor
      determining whether cells survive a cryopreservation procedure. What is not clear
      is the mechanism or route by which an external ice crystal can traverse the
      plasma membrane and cause the heterogeneous nucleation of the supercooled
      solution within the cell. We have hypothesized that one route is through
      preexisting pores in aquaporin (AQP) proteins that span the plasma membranes of
      many cell types. Since the plasma membrane of mature mouse oocytes expresses
      little AQP, we compared the ice nucleation temperature of native oocytes with
      that of oocytes induced to express AQP1 and AQP3. The oocytes were suspended in
      1.0  M ethylene glycol in PBS for 15  min, cooled in a Linkam cryostage to -7.0  
      degrees  C, induced to freeze externally, and finally cooled at 20   degrees 
      C/min to -70   degrees  C. IIF that occurred during the 20   degrees  C/min
      cooling is manifested by abrupt black flashing. The mean IIF temperatures for
      native oocytes, for oocytes sham injected with water, for oocytes expressing
      AQP1, and for those expressing AQP3 were -34, -40, -35, and -25   degrees  C
      respectively. The fact that the ice nucleation temperature of oocytes expressing
      AQP3 was 10-15   degrees  C higher than the others is consistent with our
      hypothesis. AQP3 pores can supposedly be closed by low pH or by treatment with
      double-stranded Aqp3 RNA. However, when morulae were subjected to such
      treatments, the IIF temperature still remained high. A possible explanation is
      suggested.

PMID- 21734034
TI  - Ribosomal protein S6 interacts with the latency-associated nuclear antigen of
      Kaposi's sarcoma-associated herpesvirus.
AB  - The latency-associated nuclear antigen (LANA) is central to the maintenance of
      Kaposi's sarcoma-associated herpesvirus (KSHV) and to the survival of KSHV
      carrying tumor cells. In an effort to identify interaction partners of LANA, we
      purified authentic high-molecular-weight complexes of LANA by conventional
      chromatography followed by immunoprecipitation from the BC-3 cell line. This is
      the first analysis of LANA-interacting partners that is not based on forced
      ectopic expression of LANA. Subsequent tandem mass spectrometry (MS/MS) analysis
      identified many of the known LANA-interacting proteins. We confirmed LANA's
      interactions with histones. Three classes of proteins survived our stringent four
      step purification procedure (size, heparin, anion, and immunoaffinity
      chromatography): two heat shock proteins (Hsp70 and Hsp96 precursor), signal
      recognition particle 72 (SRP72), and 10 different ribosomal proteins. These
      proteins are likely involved in structural interactions within LANA high
      molecular-weight complexes. Here, we show that ribosomal protein S6 (RPS6)
      interacts with LANA. This interaction is mediated by the N-terminal domain of
      LANA and does not require DNA or RNA. Depletion of RPS6 from primary effusion
      lymphoma (PEL) cells dramatically decreases the half-life of full-length LANA.
      The fact that RPS6 has a well-established nuclear function beyond its role in
      ribosome assembly suggests that RPS6 (and by extension other ribosomal proteins)
      contributes to the extraordinary stability of LANA.

PMID- 21734035
TI  - Enhanced control of pathogenic Simian immunodeficiency virus SIVmac239
      replication in macaques immunized with an interleukin-12 plasmid and a DNA prime
      viral vector boost vaccine regimen.
AB  - DNA priming has previously been shown to elicit augmented immune responses when
      administered by electroporation (EP) or codelivered with a plasmid encoding
      interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and
      recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved
      when incorporating these vaccination strategies into the DNA priming phase, as
      determined by pathogenic simian immunodeficiency virus SIVmac239 challenge
      outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids
      (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with
      corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose
      SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the
      median SIV peak and set point viral loads in rhesus macaques (RMs) that received
      pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads
      in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong
      suppression of viremia was observed, with intermittent "blips" in virus
      replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and
      lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12
      demonstrated a typical maximum of 1.5 log reduction in virus load. There was no
      significant difference in the overall magnitude of SIV-specific antibodies or CD8
      T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced
      a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines.
      This vaccine strategy is relevant for existing vaccine candidates entering
      clinical evaluation, and this model may provide insights into control of
      retrovirus replication.

PMID- 21734036
TI  - Evidence for a dual antiviral role of the major nuclear domain 10 component Sp100
      during the immediate-early and late phases of the human cytomegalovirus
      replication cycle.
AB  - In recent studies, the nuclear domain 10 (ND10) components PML and hDaxx were
      identified as cellular restriction factors that inhibit the initiation of human
      cytomegalovirus (HCMV) replication. The antiviral function of ND10, however, is
      antagonized by the IE1 protein, which induces ND10 disruption. Here we show that
      IE1 not only de-SUMOylates PML immediately upon infection but also directly
      targets Sp100. IE1 expression alone was sufficient to downregulate endogenous
      Sp100 independently of the presence of PML. Moreover, cotransfection experiments
      revealed that IE1 negatively interferes with the SUMOylation of all Sp100
      isoforms. The modulation of Sp100 at immediate-early (IE) times of infection,
      indeed, seemed to have an in vivo relevance for HCMV replication, since knockdown
      of Sp100 resulted in more cells initiating the viral gene expression program. In
      addition, we observed that Sp100 was degraded in a proteasome-dependent manner at
      late times postinfection, suggesting that Sp100 may play an additional antiviral
      role during the late phase. Infection experiments conducted with Sp100 knockdown
      human foreskin fibroblasts (HFFs) confirmed this hypothesis: depletion of Sp100
      resulted in augmented release of progeny virus particles compared to that from
      control cells. Consistent with this observation, we noted increased amounts of
      viral late gene products in the absence of Sp100. Importantly, this elevated late
      gene expression was not dependent on enhanced viral IE gene expression. Taken
      together, our data provide evidence that Sp100 is the first ND10-related factor
      identified that not only possesses the potential to restrict the initial stage of
      infection but also inhibits HCMV replication during the late phase.

PMID- 21734037
TI  - The TRIM5{alpha} genotype of rhesus macaques affects acquisition of simian
      immunodeficiency virus SIVsmE660 infection after repeated limiting-dose
      intrarectal challenge.
AB  - It has recently been shown that polymorphism at the rhesus macaque TRIM5 locus
      can affect simian immunodeficiency virus (SIV) replication. Here we show that
      TRIM5 alleles can also affect acquisition of SIVsmE660. Animals coexpressing the
      TRIM5(TFP) and TRIM5(CypA) alleles took significantly longer to become infected
      with SIVsmE660, but not SIVmac239, after repeated limiting-dose intrarectal
      challenge than did animals expressing other TRIM5 allele combinations. Our
      results indicate that the TRIM5 alleles can be a barrier to productive infection
      and that this should be taken into account when designing acquisition studies
      using SIVsmE660 or related viruses.

PMID- 21734038
TI  - RNA binding by a novel helical fold of b2 protein from wuhan nodavirus mediates
      the suppression of RNA interference and promotes b2 dimerization.
AB  - Wuhan nodavirus (WhNV) is a newly identified member of the Nodaviridae family
      with a bipartite genome of positive-sense RNAs. A nonstructural protein encoded
      by subgenomic RNA3 of nodaviruses, B2, serves as a potent RNA silencing
      suppressor (RSS) by sequestering RNA duplexes. We have previously demonstrated
      that WhNV B2 blocks RNA silencing in cultured Drosophila cells. However, the
      molecular mechanism by which WhNV B2 functions remains unknown. Here, we
      successfully established an RNA silencing system in cells derived from Pieris
      rapae, a natural host of WhNV, by introducing into these cells double-stranded
      RNA (dsRNA)-expressing plasmids or chemically synthesized small interfering RNAs
      (siRNAs). Using this system, we revealed that the WhNV B2 protein inhibited Dicer
      mediated dsRNA cleavage and the incorporation of siRNA into the RNA-induced
      silencing complex (RISC) by sequestering dsRNA and siRNA. Based on the modeled B2
      3-dimensional structure, serial single alanine replacement mutations and N
      terminal deletion analyses showed that the RNA-binding domain of B2 is formed by
      its helices alpha2 and alpha3, while helix alpha1 mediates B2 dimerization.
      Furthermore, positive feedback between RNA binding and B2 dimerization was
      uncovered by gel shift assay and far-Western blotting, revealing that B2
      dimerization is required for its binding to RNA, whereas RNA binding to B2 in
      turn promotes its dimerization. All together, our findings uncovered a novel RNA
      binding mode of WhNV B2 and provided evidence that the promotion effect of RNA
      binding on dimerization exists in a viral RSS protein.

PMID- 21734039
TI  - Human cytomegalovirus infection maintains mTOR activity and its perinuclear
      localization during amino acid deprivation.
AB  - The mammalian target of rapamycin (mTOR) kinase is present in 2 functionally
      distinct complexes, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). Active mTORC1
      mediates phosphorylation of eIF4E-binding protein (4E-BP) and p70 S6 kinase
      (S6K), which is important for maintaining translation. During human
      cytomegalovirus (HCMV) infection, cellular stress responses are activated that
      normally inhibit mTORC1; however, previous data show that HCMV infection
      circumvents stress responses and maintains mTOR kinase activity. Amino acid
      deprivation is a stress response that normally inhibits mTORC1 activity. Amino
      acids can signal to mTORC1 through the Rag proteins, which promote the
      colocalization of mTORC1 with its activator Rheb-GTP in a perinuclear region,
      thereby inducing 4E-BP and S6K phosphorylation. As expected, our results show
      that amino acid depletion in mock-infected cells caused loss of mTORC1 activity
      and loss of the perinuclear localization; however, there was no loss of activity
      or perinuclear localization in HCMV-infected cells where the perinuclear
      localization of Rheb-GTP and mTOR coincided with the perinuclear assembly
      compartment (AC). This suggested that HCMV infection bypasses normal Rag
      dependent amino acid signaling. This was demonstrated by short hairpin RNA
      (shRNA) depletion of Rag proteins, which had little effect on mTORC1 activity in
      infected cells but inhibited activity in mock-infected cells. Our data show that
      HCMV maintains mTORC1 activity in an amino acid- and Rag-independent manner
      through the colocalization of mTOR and Rheb-GTP, which occurs in association with
      the formation of the AC, thus bypassing inhibition that may result from lowered
      amino acid levels.

PMID- 21734040
TI  - Interaction and interdependent packaging of tegument protein UL11 and
      glycoprotein e of herpes simplex virus.
AB  - The UL11 tegument protein of herpes simplex virus plays a critical role in the
      secondary envelopment; however, the mechanistic details remain elusive. Here, we
      report a new function of UL11 in the budding process in which it directs
      efficient acquisition of glycoprotein E (gE) via a direct interaction. In vitro
      binding assays showed that the interaction required only the first 28, membrane
      proximal residues of the cytoplasmic tail of gE, and the C-terminal 26 residues
      of UL11. A second, weaker binding site was also found in the N-terminal half of
      UL11. The significance of the gE-UL11 interaction was subsequently investigated
      with viral deletion mutants. In the absence of the gE tail, virion packaging of
      UL11, but not other tegument proteins such as VP22 and VP16, was reduced by at
      least 80%. Reciprocally, wild-type gE packaging was also drastically reduced by
      about 87% in the absence of UL11, and this defect could be rescued in trans by
      expressing U(L)11 at the U(L)35 locus. Surprisingly, a mutant that lacks the C
      terminal gE-binding site of UL11 packaged nearly normal amounts of gE despite its
      strong interaction with the gE tail in vitro, indicating that the interaction
      with the UL11 N terminus may be important. Mutagenesis studies of the UL11 N
      terminus revealed that the association of UL11 with membrane was not required for
      this function. In contrast, the UL11 acidic cluster motif was found to be
      critical for gE packaging and was not replaceable with foreign acidic clusters.
      Together, these results highlight an important role of UL11 in the acquisition of
      glycoprotein-enriched lipid bilayers, and the findings may also have important
      implications for the role of UL11 in gE-mediated cell-to-cell spread.

PMID- 21734041
TI  - epitopes immediately below the base of the V3 loop of gp120 as targets for the
      initial autologous neutralizing antibody response in two HIV-1 subtype B-infected
      individuals.
AB  - Epitopes that drive the initial autologous neutralizing antibody response in HIV
      1-infected individuals could provide insights for vaccine design. Although highly
      strain specific, these epitopes are immunogenic, vulnerable to antibody attack on
      infectious virus, and could be involved in the ontogeny of broadly neutralizing
      antibody responses. To delineate such epitopes, we used site-directed
      mutagenesis, autologous plasma samples, and autologous monoclonal antibodies to
      map the amino acid changes that led to escape from the initial autologous
      neutralizing antibody response in two HIV-1 subtype B-infected individuals.
      Additional mapping of the epitopes was accomplished by using alanine scanning
      mutagenesis. Escape in the two individuals occurred by different pathways, but
      the responses in both cases appeared to be directed against the same region of
      gp120. In total, three amino acid positions were identified that were
      independently associated with autologous neutralization. Positions 295 and 332
      are located immediately before and after the N- and C-terminal cysteines of the
      V3 loop, respectively, the latter of which affected an N-linked glycan that was
      critical to the neutralization epitope. Position 415 affected an N-linked glycan
      at position 413 in the C terminus of V4 that might mask epitopes near the base of
      V3. All three sites lie in close proximity on a four-stranded antiparallel sheet
      on the outer domain of gp120. We conclude that a region just below the base of
      the V3 loop, near the coreceptor binding domain of gp120, can be a target for
      autologous neutralization.

PMID- 21734042
TI  - Inhibition of HIV-1 integration in ex vivo-infected CD4 T cells from elite
      controllers.
AB  - Elite controllers spontaneously maintain undetectable levels of HIV-1 replication
      for reasons that remain unclear. Here, we show that in elite controllers, direct
      ex vivo infection of purified CD4 T cells without prior in vitro activation
      results in disproportionately low levels of integrated HIV-1 DNA relative to the
      quantity of reverse transcripts, while the levels of two-long terminal repeat (2
      LTR) circles were excessively elevated relative to those of integrated HIV-1 DNA.
      This indicates that chromosomal HIV-1 integration is inhibited in ex vivo
      infected CD4 T cells from elite controllers. This defect in HIV-1 integration was
      unrelated to p21, a host protein that can restrict early HIV-1 replication steps,
      and was not visible following infection of in vitro-activated CD4 T cells from
      elite controllers. These data contribute to increasing evidence that intrinsic
      inhibition of specific HIV-1 replication steps plays an important role in the
      ability of elite controllers to maintain undetectable viral loads.

PMID- 21734043
TI  - The histone acetyltransferase CLOCK is an essential component of the herpes
      simplex virus 1 transcriptome that includes TFIID, ICP4, ICP27, and ICP22.
AB  - Studies published elsewhere have shown that the herpes simplex virus regulatory
      protein ICP0 interacts with BMAL1, a partner and regulator of circadian histone
      acetyltransferase CLOCK, that both proteins localize at ND10 bodies and are
      stabilized by viral proteins, that enzymatically active CLOCK partially
      complements DeltaICP0 mutants, and that silencing of CLOCK suppresses the
      expression of viral genes. Here we report that CLOCK is a component of the
      transcriptional complex that includes TFIID, ICP4, ICP27, and ICP22. The results
      suggest that the CLOCK histone acetyltransferase is a component of the viral
      transcriptional machinery throughout the replicative cycle of the virus and that
      ICP27 and ICP22 initiate their involvement in viral gene expression as components
      of viral transcriptome.

PMID- 21734044
TI  - Direct and specific binding of the UL16 tegument protein of herpes simplex virus
      to the cytoplasmic tail of glycoprotein E.
AB  - The UL16 tegument protein of herpes simplex virus (HSV) is conserved throughout
      all of the herpesvirus families. Previous studies have shown that the binding of
      HSV to heparan sulfate molecules on the host cell triggers the release of UL16
      from the capsid, but the mechanism by which the signal is sent from the virion
      surface into the tegument is unknown. Here, we report that a glutathione S
      transferase chimera bearing the cytoplasmic tail of viral glycoprotein E (gE) is
      capable of binding to UL16 in lysates of eukaryotic cells or purified from
      bacteria. Moreover, mass spectrometry studies of native-UL16 complexes purified
      from infected cells also revealed the presence of gE. Proof that UL16-gE can
      interact within cells required the fortuitous discovery of a mutant possessing
      only the first 155 residues of UL16. Confocal microscopy of cotransfected cells
      revealed that this mutant colocalized with gE in the cytoplasm, whereas it was
      found throughout the cytoplasm and nucleus when expressed alone. In contrast, the
      full-length UL16 molecule was very poorly capable of finding gE. Moreover,
      membrane flotation assays showed that UL16(1-155) was able to float to the top of
      sucrose step gradients when coexpressed with gE, whereas full-length UL16 was
      not. Thus, the discovery of the UL16(1-155) mutant confirmed the specific in
      vitro interaction with gE and provides evidence that a binding domain at the N
      terminus of UL16 may be controlled by a regulatory domain within the C terminus.
      These findings suggest the possibility that the UL16-gE interaction may play
      roles in the tegument signaling mechanism, virus budding, and the gE-mediated
      mechanism of cell-to-cell spread.

PMID- 21734045
TI  - Herpes simplex virus 1 protein kinase Us3 and major tegument protein UL47
      reciprocally regulate their subcellular localization in infected cells.
AB  - Us3 is a serine-threonine protein kinase encoded by herpes simplex virus 1 (HSV
      1). We have identified UL47, a major virion protein, as a novel physiological
      substrate of Us3. In vitro kinase assays and systematic analysis of mutations at
      putative Us3 phosphorylation sites near the nuclear localization signal of UL47
      showed that serine at residue 77 (Ser-77) was required for Us3 phosphorylation of
      UL47. Replacement of UL47 Ser-77 by alanine produced aberrant accumulation of
      UL47 at the nuclear rim and impaired the nuclear localization of UL47 in a
      significant fraction of infected cells. The same defect in UL47 localization was
      produced by an amino acid substitution in Us3 that inactivated its protein kinase
      activity. In contrast, a phosphomimetic mutation at UL47 Ser-77 restored wild
      type nuclear localization. The UL47 S77A mutation also reduced viral replication
      in the mouse cornea and the development of herpes stromal keratitis in mice. In
      addition, UL47 formed a stable complex with Us3 in infected cells, and nuclear
      localization of Us3 was significantly impaired in the absence of UL47. These
      results suggested that Us3 phosphorylation of UL47 Ser-77 promoted the nuclear
      localization of UL47 in cell cultures and played a critical role in viral
      replication and pathogenesis in vivo. Furthermore, UL47 appeared to be required
      for efficient nuclear localization of Us3 in infected cells. Therefore, Us3
      protein kinase and its substrate UL47 demonstrated a unique regulatory feature in
      that they reciprocally regulated their subcellular localization in infected
      cells.

PMID- 21734046
TI  - HIV-specific functional antibody responses in breast milk mirror those in plasma
      and are primarily mediated by IgG antibodies.
AB  - Despite months of mucosal virus exposure, the majority of breastfed infants born
      to HIV-infected mothers do not become infected, raising the possibility that
      immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)
      specific antibodies are present in the milk of HIV-infected mothers, but little
      is known about their virus-specific functions. In this study, HIV Env-specific
      antibody binding, autologous and heterologous virus neutralization, and antibody
      dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma
      of 41 HIV-infected lactating women. Although IgA is the predominant antibody
      isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV
      Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in
      milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet the response
      in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus
      neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001) in
      milk were directly correlated with that in the systemic compartment but were 2
      log units lower in magnitude. Autologous neutralization was rarely detected in
      milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env
      binding IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r
      = 0.17 and P = 0.30). Moreover, IgGs purified from milk and plasma had equal
      neutralizing potencies against a tier 1 virus (r = 0.65; P < 0.0001), whereas
      only 1 out of 35 tested non-IgG milk fractions had detectable neutralization.
      These results suggest that plasma-derived IgG antibodies mediate the majority of
      the low-level HIV neutralization and ADCC activity in breast milk.

PMID- 21734047
TI  - Productive dengue virus infection of human endothelial cells is directed by
      heparan sulfate-containing proteoglycan receptors.
AB  - Dengue virus causes leakage of the vascular endothelium, resulting in dengue
      hemorrhagic fever and dengue shock syndrome. The endothelial cell lining of the
      vasculature regulates capillary permeability and is altered by immune and
      chemokine responses which affect fluid barrier functions of the endothelium. Our
      findings indicate that human endothelial cells are highly susceptible to
      infection by dengue virus (type 4). We found that dengue virus productively
      infects ~80% of primary human endothelial cells, resulting in the rapid release
      of ~10(5) virions 1 day postinfection. Analysis of potential inhibitors of dengue
      virus entry demonstrated that antibodies and ligands to integrins and cellular
      receptors were unable to inhibit dengue virus infection of endothelial cells. In
      contrast, pretreating cells with heparin or heparan sulfate resulted in a 60 to
      80% reduction in dengue virus-infected cells, and pretreatment of endothelial
      cells with heparinase III or protease reduced dengue infectivity by >80%. Dengue
      virus bound specifically to resin immobilized heparin, and binding was
      competitively inhibited by excess heparin but not other ligands. Collectively,
      these findings suggest that dengue virus specifically attaches to heparan sulfate
      containing proteoglycan receptors on endothelial cells. Following attachment to
      human endothelial cell receptors, dengue virus causes a highly productive
      infection that has the potential to increase viral dissemination and viremia.
      This provides the potential for dengue virus-infected endothelial cells to
      directly alter barrier functions of the endothelium, contribute to enhancement of
      immune cell activation, and serve as potential targets of immune responses which
      play a central role in dengue pathogenesis.

PMID- 21734048
TI  - Vesicular stomatitis virus has extensive oncolytic activity against human
      sarcomas: rare resistance is overcome by blocking interferon pathways.
AB  - Oncolytic viruses have been tested against many carcinomas of ectodermal and
      endodermal origin; however, sarcomas, arising from mesoderm, have received
      relatively little attention. Using 13 human sarcomas representing seven tumor
      types, we assessed the efficiency of infection, cytolysis, and replication of
      green fluorescent protein (GFP)-expressing vesicular stomatitis virus (VSV) and
      its oncolytically enhanced mutant VSV-rp30a. Both viruses efficiently infected
      and killed 12 of 13 sarcomas. VSV-rp30a showed a faster rate of infection and
      replication. In vitro and in vivo, VSV was selective for sarcomas compared with
      normal mesoderm. A single intravenous injection of VSV-rp30a selectively infected
      all subcutaneous human sarcomas tested in mice and arrested the growth of tumors
      that otherwise grew 11-fold. In contrast to other sarcomas, synovial sarcoma
      SW982 demonstrated remarkable resistance, even to high titers of virus
      (multiplicity of infection [MOI] of 100). We found no dysfunction in VSV binding
      or internalization. SW982 also resisted infection by human cytomegalovirus and
      Sindbis virus, suggesting a virus resistance mechanism based on an altered
      antiviral state. Quantitative reverse transcriptase (qRT)-PCR analysis revealed a
      heightened basal expression of interferon-stimulated genes (ISGs). Pretreatment,
      but not cotreatment, with interferon attenuators valproate, Jak1 inhibitor, or
      vaccinia virus B18R protein rendered SW982 highly susceptible, and this
      correlated with downregulation of ISG expression. Jak1 inhibitor pretreatment
      also enhanced susceptibility in moderately VSV-resistant liposarcoma and bladder
      carcinoma. Overall, we find that the potential efficacy of VSV as an oncolytic
      agent extends to nonhematologic mesodermal tumors and that unusually strong
      resistance to VSV oncolysis can be overcome with interferon attenuators.

PMID- 21734049
TI  - Contribution of E3-ubiquitin ligase activity to HIV-1 restriction by
      TRIM5alpha(rh): structure of the RING domain of TRIM5alpha.
AB  - TRIM5alpha(rh) is a cytosolic protein that potently restricts HIV-1 before
      reverse transcription. TRIM5alpha(rh) is composed of four different domains:
      RING, B-box 2, coiled coil, and B30.2(SPRY). The contribution of each of these
      domains to restriction has been extensively studied, with the exception of the
      RING domain. The RING domain of TRIM5alpha exhibits E3-ubiquitin ligase activity,
      but the contribution of this activity to the restriction of HIV-1 is not known.
      To test the hypothesis that the E3-ubiquitin ligase activity of the RING domain
      modulates TRIM5alpha(rh) restriction of HIV-1, we correlated the E3-ubiquitin
      ligase activity of a panel of TRIM5alpha(rh) RING domain variants with the
      ability of these mutant proteins to restrict HIV-1. For this purpose, we first
      solved the nuclear magnetic resonance structure of the RING domain of TRIM5alpha
      and defined potential functional regions of the RING domain by homology to other
      RING domains. With this structural information, we performed a systematic
      mutagenesis of the RING domain regions and tested the TRIM5alpha RING domain
      variants for the ability to undergo self-ubiquitylation. Several residues,
      particularly the ones on the E2-binding region of the RING domain, were defective
      in their self-ubiquitylation ability. To correlate HIV-1 restriction to self
      ubiquitylation, we used RING domain mutant proteins that were defective in self
      ubiquitylation but preserve important properties required for potent restriction
      by TRIM5alpha(rh), such as capsid binding and higher-order self-association. From
      these investigations, we found a set of residues that when mutated results in
      TRIM5alpha molecules that lost both the ability to potently restrict HIV-1 and
      their self-ubiquitylation activity. Remarkably, all of these changes were in
      residues located in the E2-binding region of the RING domain. Overall, these
      results demonstrate a role for TRIM5alpha self-ubiquitylation in the ability of
      TRIM5alpha to restrict HIV-1.

PMID- 21734050
TI  - Functional genomics reveals the induction of inflammatory response and
      metalloproteinase gene expression during lethal Ebola virus infection.
AB  - Ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and
      nonhuman primates with mortality rates of up to 90%. Previous studies with Zaire
      Ebola virus (ZEBOV), mouse-adapted virus (MA-ZEBOV), and mutant viruses (ZEBOV
      NP(ma), ZEBOV-VP24(ma), and ZEBOV-NP/VP24(ma)) allowed us to identify the
      mutations in viral protein 24 (VP24) and nucleoprotein (NP) responsible for
      acquisition of high virulence in mice. To elucidate specific molecular signatures
      associated with lethality, we compared global gene expression profiles in spleen
      samples from mice infected with these viruses and performed an extensive
      functional analysis. Our analysis showed that the lethal viruses (MA-ZEBOV and
      ZEBOV-NP/VP24(ma)) elicited a strong expression of genes 72 h after infection. In
      addition, we found that although the host transcriptional response to ZEBOV
      VP24(ma) was nearly the same as that to ZEBOV-NP/VP24(ma), the contribution of a
      mutation in the NP gene was required for a lethal phenotype. Further analysis
      indicated that one of the most relevant biological functions differentially
      regulated by the lethal viruses was the inflammatory response, as was the
      induction of specific metalloproteinases, which were present in our newly
      identify functional network that was associated with Ebola virus lethality. Our
      results suggest that this dysregulated proinflammatory response increased the
      severity of disease. Consequently, the newly discovered molecular signature could
      be used as the starting point for the development of new drugs and therapeutics.
      To our knowledge, this is the first study that clearly defines unique molecular
      signatures associated with Ebola virus lethality.

PMID- 21734051
TI  - Nuclear accumulation of the papillomavirus E1 helicase blocks S-phase progression
      and triggers an ATM-dependent DNA damage response.
AB  - Replication of the papillomavirus genome is initiated by the assembly of a
      complex between the viral E1 and E2 proteins at the origin. The E1 helicase is
      comprised of a C-terminal ATPase/helicase domain, a central domain that binds to
      the origin, and an N-terminal regulatory region that contains nuclear import and
      export signals mediating its nucleocytoplasmic shuttling. We previously reported
      that nuclear accumulation of E1 has a deleterious effect on cellular
      proliferation which can be prevented by its nuclear export. Here we have shown
      that nuclear accumulation of E1 from different papillomavirus types blocks cell
      cycle progression in early S phase and triggers the activation of a DNA damage
      response (DDR) and of the ATM pathway in a manner that requires both the origin
      binding and ATPase activities of E1. Complex formation with E2 reduces the
      ability of E1 to induce a DDR but does not prevent cell cycle arrest. Transient
      viral DNA replication still occurs in S-phase-arrested cells but surprisingly is
      neither affected by nor dependent on induction of a DDR and of the ATM kinase.
      Finally, we provide evidence that a DDR is also induced in human papillomavirus
      type 31 (HPV31)-immortalized keratinocytes expressing a mutant E1 protein
      defective for nuclear export. We propose that nuclear export of E1 prevents cell
      cycle arrest and the induction of a DDR during the episomal maintenance phase of
      the viral life cycle and that complex formation with E2 further safeguards
      undifferentiated cells from undergoing a DDR when E1 is in the nucleus.

PMID- 21734052
TI  - Amino acid residues 253 and 591 of the PB2 protein of avian influenza virus A
      H9N2 contribute to mammalian pathogenesis.
AB  - We investigated the tropism, host responses, and virulence of two variants of
      A/Quail/Hong Kong/G1/1997 (H9N2) (H9N2/G1) with D253N and Q591K in the PB2
      protein in primary human macrophages and bronchial epithelium in vitro and in
      mice in vivo. Virus with PB2 D253N and Q591K had greater polymerase activity in
      minireplicon assays, induced more tumor necrosis factor alpha (TNF-alpha) in
      human macrophages, replicated better in differentiated normal human bronchial
      epithelial (NHBE) cells, and was more pathogenic for mice. Taken together, our
      studies help define the viral genetic determinants that contribute to
      pathogenicity of H9N2 viruses.

PMID- 21734053
TI  - High cell-free virus load and robust autologous humoral immune responses in
      breast milk of simian immunodeficiency virus-infected african green monkeys.
AB  - The design of immunologic interventions to prevent postnatal transmission of
      human immunodeficiency virus (HIV) will require identification of protective
      immune responses in this setting. Simian immunodeficiency virus (SIV)-infected
      rhesus monkeys (RMs), a species that develops an AIDS-like illness following
      experimental infection, transmit the virus at a high rate during breastfeeding.
      In contrast, postnatal transmission of SIV occurs rarely or not at all in
      natural, asymptomatic primate hosts of SIV. These contrasting transmission
      patterns provide a unique opportunity to study mechanisms that evolved to protect
      suckling infants from SIV infection. We compared the virologic and immunologic
      properties of milk of SIV-infected and uninfected natural hosts of SIV, African
      green monkeys (AGMs), to that of RMs. Interestingly, despite a low number of milk
      CD4(+) T lymphocytes in uninfected AGMs, milk virus RNA load in SIV-infected AGMs
      was comparable to that of SIV-infected RMs and that in AGM plasma. This
      observation is in contrast to the relatively low virus load in milk compared to
      that in plasma of SIV-infected RMs and HIV-infected women. Milk of SIV-infected
      AGMs also displayed robust virus-specific cellular immune responses. Importantly,
      an autologous challenge virus-specific neutralization response was detected in
      milk of five of six SIV-infected AGMs that was comparable in magnitude to that in
      plasma. In contrast, autologous challenge virus neutralization was not detectable
      in milk of SIV-infected RMs. The autologous virus-specific adaptive immune
      responses in breast milk of AGMs may contribute to impedance of virus
      transmission in the infant oral/gastrointestinal tract and the rarity of
      postnatal virus transmission in natural hosts of SIV.

PMID- 21734054
TI  - The papillomavirus E1 helicase activates a cellular DNA damage response in viral
      replication foci.
AB  - The papillomavirus E1 and E2 proteins are essential for viral genome replication.
      E1 is a helicase that unwinds the viral origin and recruits host cellular factors
      to replicate the viral genome. E2 is a transcriptional regulator that helps
      recruit the E1 helicase to the origin and also plays a role in genome
      partitioning. We find that when coexpressed, the E1 and E2 proteins from several
      papillomavirus types localize to defined nuclear foci and result in growth
      suppression of the host cells. Growth suppression was due primarily to E1 protein
      function, and nuclear expression of E1 was accompanied by activation of a DNA
      damage response, resulting in phosphorylation of ATM, Chk2, and H2AX. Growth
      suppression and ATM activation required the ATPase and origin-specific binding
      functions of the E1 protein and resulted in active DNA repair, as evidenced by
      incorporation of nucleotide analogs and detection of free DNA ends. In the
      presence of the E2 protein, these activities became localized to nuclear foci. We
      postulate that these foci represent viral replication factories and that a
      cellular DNA damage response is activated to facilitate replication of viral DNA.

PMID- 21734055
TI  - Parasite-mediated upregulation of NK cell-derived gamma interferon protects
      against severe highly pathogenic H5N1 influenza virus infection.
AB  - Outbreaks of influenza A viruses are associated with significant human morbidity
      worldwide. Given the increasing resistance to the available influenza drugs, new
      therapies for the treatment of influenza virus infection are needed. An
      alternative approach is to identify products that enhance a protective immune
      response. In these studies, we demonstrate that infecting mice with the Th1
      inducing parasite Toxoplasma gondii prior to highly pathogenic avian H5N1
      influenza virus infection led to decreased lung viral titers and enhanced
      survival. A noninfectious fraction of T. gondii soluble antigens (STAg) elicited
      an immune response similar to that elicited by live parasites, and administration
      of STAg 2 days after H5N1 influenza virus infection enhanced survival, lowered
      viral titers, and reduced clinical disease. STAg administration protected H5N1
      virus-infected mice lacking lymphocytes, suggesting that while the adaptive
      immune response was not required for enhanced survival, it was necessary for STAg
      mediated viral clearance. Mechanistically, we found that administration of STAg
      led to increased production of gamma interferon (IFN-gamma) from natural killer
      (NK) cells, which were both necessary and sufficient for survival. Further,
      administration of exogenous IFN-gamma alone enhanced survival from H5N1 influenza
      virus infection, although not to the same level as STAg treatment. These studies
      demonstrate that a noninfectious T. gondii extract enhances the protective immune
      response against severe H5N1 influenza virus infections even when a single dose
      is administered 2 days postinfection.

PMID- 21734056
TI  - Suppression of STAT-1 expression by human papillomaviruses is necessary for
      differentiation-dependent genome amplification and plasmid maintenance.
AB  - High-risk human papillomaviruses (HPVs) infect stratified epithelia to establish
      persistent infections that maintain low-copy-number episomes in infected basal
      cells. Amplification of viral genomes occurs upon keratinocyte differentiation,
      followed by virion synthesis. During persistent HPV infections, viral proteins
      act to evade surveillance by both innate and adaptive immune responses. One of
      the primary pathways regulating the innate immune response is the JAK/STAT
      pathway. Our studies indicate that the expression of STAT-1, but not other
      members of interferon (IFN)-stimulated gene factor 3 (ISGF-3) complex such as
      STAT-2 and IFN regulatory factor 9 (IRF9), is selectively suppressed by HPV
      proteins at the level of transcription. Both E6 and E7 oncoproteins independently
      suppress the expression of STAT-1, and mutational analyses indicate that the E6
      targeting E6-associated protein (E6AP) is responsible for suppression. The levels
      of STAT-1 proteins increase upon differentiation of both normal and HPV-positive
      cells but are still significantly reduced in the latter cells. Transient
      restoration of STAT-1 levels in HPV-positive cells using recombinant retroviruses
      significantly impaired viral amplification upon differentiation while long-term
      increases abrogated maintenance of episomes. Similarly, increased levels of STAT
      1 induced by gamma interferon treatment inhibited HPV genome amplification upon
      differentiation. Overall, our findings demonstrate that suppression of STAT-1
      expression by HPV proteins is necessary for genome amplification and maintenance
      of episomes, suggesting an important role for this activity in viral
      pathogenesis.

PMID- 21734057
TI  - Antigenic drift in H5N1 avian influenza virus in poultry is driven by mutations
      in major antigenic sites of the hemagglutinin molecule analogous to those for
      human influenza virus.
AB  - H5N1 highly pathogenic avian influenza virus has been endemic in poultry in Egypt
      since 2008, notwithstanding the implementation of mass vaccination and culling of
      infected birds. Extensive circulation of the virus has resulted in a progressive
      genetic evolution and an antigenic drift. In poultry, the occurrence of antigenic
      drift in avian influenza viruses is less well documented and the mechanisms
      remain to be clarified. To test the hypothesis that H5N1 antigenic drift is
      driven by mechanisms similar to type A influenza viruses in humans, we generated
      reassortant viruses, by reverse genetics, that harbored molecular changes
      identified in genetically divergent viruses circulating in the vaccinated
      population. Parental and reassortant phenotype viruses were antigenically
      analyzed by hemagglutination inhibition (HI) test and microneutralization (MN)
      assay. The results of the study indicate that the antigenic drift of H5N1 in
      poultry is driven by multiple mutations primarily occurring in major antigenic
      sites at the receptor binding subdomain, similarly to what has been described for
      human influenza H1 and H3 subtype viruses.

PMID- 21734058
TI  - Spontaneous pulmonary alveolar proteinosis in captive "moustached tamarins"
      (Saguinus mystax).
AB  - Pulmonary alveolar proteinosis is a rare human disease characterized by
      accumulation of surfactant in alveoli without generating an inflammatory
      response. Lung lesions resembling pulmonary alveolar proteinosis were observed in
      7 adult tamarins (5 males and 2 females). Gross lesions were characterized by
      areas of discoloration, slight bulging over the lung parenchyma, and occasional
      consolidation. Histologic examination of tamarin lung samples revealed intra
      alveolar accumulation of amorphous, amphophilic, periodic acid-Schiff-positive,
      finely granular to dense material. In some cases, type II pneumocyte hypertrophy
      and hyperplasia were observed with pleural and septal thickening and fibrosis.
      Large numbers of intra-alveolar foamy macrophages were noted surrounding and/or
      in the vicinity of the lesions. Immunohistochemical analysis of the lung lesions
      using polyclonal (surfactant proteins A, B, and C) and monoclonal (surfactant
      protein D) antibodies revealed the granular material to be composed largely of
      surfactant protein B, followed by surfactant protein A. Surfactant proteins C and
      D were present in lesser quantities, with the latter observed surrounding the
      lipoproteinaceous deposits. Transmission electron microscopy of the affected
      lungs showed numerous, irregularly shaped osmiophilic lamellar bodies in type II
      pneumocytes. The cytoplasm in alveolar macrophages was expanded, containing
      ingested surfactant with swollen mitochondria and rough endoplasmic reticulum.
      Thoracic radiographs, available in 1 animal, depicted the lesions as small
      multifocal opacities randomly distributed in cranial and diaphragmatic lung
      lobes. This is, to the authors' knowledge, the first report of spontaneous
      pulmonary alveolar proteinosis in nonhuman primates.

PMID- 21734059
TI  - Erythrocyte fatty acid composition is associated with the risk of hypertension in
      middle-aged and older women.
AB  - Experimental studies have suggested different effects of various fats on blood
      pressure. However, epidemiologic evidence of these relations remains limited and
      inconsistent. We therefore assessed the association of fatty acid (FA)
      composition in erythrocyte membranes with the risk of hypertension. We selected
      516 cases of incident hypertension and 516 matched controls during 12.9 y of
      follow-up in the Women's Health Study. Erythrocyte FA was measured in baseline
      bloods using GC. After controlling matching factors and lifestyle factors,
      erythrocyte SFA showed a positive association, whereas total cis PUFA, cis (n-3)
      PUFA, and the ratio of PUFA:SFA (PS ratio) showed an inverse association with the
      risk of hypertension. The multivariable RR of hypertension across the increasing
      quartiles of erythrocyte FA subtypes were 1.00, 1.19, 1.44, and 1.76 for total
      SFA; 1.00, 0.84, 0.88, and 0.56 for total cis PUFA; 1.00, 0.87, 0.66, and 0.65
      for cis (n-3) PUFA; and 1.00, 0.99, 0.70, and 0.51 for the PS ratio. After
      further adjusting for obesity-related metabolic factors, these associations were
      attenuated and remained significant only for the PS ratio. cis MUFA, cis (n-6)
      PUFA, and trans unsaturated FA in erythrocyte membranes were not associated with
      the risk of hypertension. Our study showed that FA composition in erythrocyte
      membranes is associated with the risk of hypertension in middle-aged and older
      women. However, after controlling for obesity-related metabolic factors, the
      associations remained significant only for the PS ratio.

PMID- 21734060
TI  - Astaxanthin-rich extract from the green alga Haematococcus pluvialis lowers
      plasma lipid concentrations and enhances antioxidant defense in apolipoprotein E
      knockout mice.
AB  - Dyslipidemia and oxidative stress contribute to atherogenesis. Astaxanthin (ASTX)
      is a red-colored carotenoid well known for its high antioxidant capacity.
      However, its effects on lipid metabolism and antioxidant defense mechanisms have
      received only limited investigation. We fed male apoE knockout (apoE)(-/-) mice,
      a mouse model for atherosclerosis, a high-fat (15%)/high-cholesterol (0.2%) diet
      alone (control) or supplemented with ASTX-rich Hematococcus pluvialis extract
      (0.03% ASTX by weight) for 4 wk. ASTX-fed apoE(-/-) mice had significantly lower
      plasma total cholesterol and TG concentrations than controls, but body weight and
      plasma alanine aminotransferase and aspartate aminotransferase did not differ
      between the groups. qRT-PCR analysis demonstrated significantly greater mRNA
      levels of LDL receptor (LDLR), 3-hydroxy-3-methylglutaryl CoA reductase, and
      sterol regulatory element binding protein 2 (SREBP-2) and greater mature SREBP-2
      protein in the livers of ASTX-fed mice, indicating that increased LDLR expression
      may be responsible for the hypocholesterolemic effect of ASTX. Hepatic lipogenic
      gene expression was not altered, but carnitine palmitoyl transferase 1, acetyl
      CoA carboxylase beta, and acyl-CoA oxidase mRNA abundance were significantly
      increased by ASTX supplementation, suggesting the TG-lowering effect of ASTX may
      be due to increased fatty acid beta-oxidation in the liver. Expression of the
      nuclear factor E2 related factor 2-responsive endogenous antioxidant gene also
      was induced with concomitantly lower glutathione disulfide levels in the livers
      of ASTX-fed apoE(-/-) mice compared to controls. In conclusion, these results
      suggest that supplementation of ASTX-rich H. pluvialis extract improves
      cholesterol and lipid metabolism as well as antioxidant defense mechanisms, all
      of which could help mitigate the progression of atherosclerosis.

PMID- 21734061
TI  - Less traditional diets in Chinese mothers and children are similarly linked to
      socioeconomic and cohort factors but vary with increasing child age.
AB  - Global shifts toward an increasingly Western diet and rises in nutrition-related
      noncommunicable diseases necessitate systematic examination of dietary change in
      adults and children. This study longitudinally examined mother and child dietary
      intakes and their relationship with socioeconomic factors across 4 mutually
      exclusive cohorts followed over 6- to 7-y time periods (cohort A: 1991-1997,
      cohort B: 1993-2000, cohort C: 1997-2004, cohort D: 2000-2006). The cohorts
      included 966 mother-child pairs (children 3-5 y at baseline) from the China
      Health and Nutrition Survey. Dietary intake was assessed using 24-h recall and
      household food consumption data; dietary variables were the percentage of total
      energy from animal-source foods (ASF), fats/oils, and grains. Mother-child
      comparison of dietary variables used average annual change measures, Spearman
      partial correlations, random effects models, and seemingly unrelated regression
      models and estimation. Whereas children were earlier adopters and maintainers of
      a less traditional Chinese diet, mothers experienced greater shifts away from the
      traditional Chinese diet with increasing child age. Mother-child correlations for
      the dietary variables ranged from 0.46 to 0.89 (P < 0.001). Similar increased
      intake of ASF and decreased intake of grains were reported for mothers and
      children of urban (vs. rural) residence and with higher levels of maternal
      education (P < 0.001). A comparable cohort effect was shown, with mothers and
      children consuming a less traditional Chinese diet in the later (C and D)
      compared to earlier (A and B) cohorts (P < 0.05). Our findings provide insight
      into dietary changes in mothers and children within the context of a rapidly
      changing nutrition and socioeconomic environment.

PMID- 21734062
TI  - Bacterial vaginosis is associated with variation in dietary indices.
AB  - Bacterial vaginosis (BV) is a common condition of unknown etiology and has been
      linked to adverse reproductive and obstetric health outcomes. Prior dietary
      research on BV has focused on specific macro- and micronutrients, but not dietary
      indices. We assessed the relationship between BV and selected dietary indicators
      among a cohort of 1735 nonpregnant women ages 15-44 y from Birmingham, Alabama.
      Annual intake was assessed with the Block98 FFQ, and the glycemic index, glycemic
      load (GL), and Healthy Eating Index were calculated by the Block Dietary Data
      System. The Naturally Nutrient Rich (NNR) score was also calculated. Vaginal
      flora was evaluated using Nugent Gram-stain criteria. Crude OR and adjusted OR
      were determined by multinomial and logistic regression in cross-sectional and
      prospective analyses, respectively. Participants were predominantly African
      American (85.5%) aged 25.3 +/- 6.8 y (mean +/- SD). Per 10-unit increase, GL was
      positively (adjusted OR = 1.01, 95% CI = 1.00-1.03) and NNR was negatively
      (adjusted OR = 0.93, 95% CI = 0.88-0.99) associated with BV compared to normal
      vaginal flora. In prospective analyses, only GL was associated with BV
      progression (adjusted OR = 1.03, 95% CI = 1.00-1.05) and persistence (adjusted OR
      = 1.02, 95% CI = 1.01-1.04) after adjustment. Both GL and NNR were associated
      with greater BV prevalence and GL was associated with an increase in BV
      persistence and acquisition. These results suggest that diet composition may
      contribute to vaginal flora imbalances and be important for elucidating the
      etiology of BV.

PMID- 21734063
TI  - Randomized trial of the immunogenicity and safety of the Hepatitis B vaccine
      given in an accelerated schedule coadministered with the human papillomavirus
      type 16/18 AS04-adjuvanted cervical cancer vaccine.
AB  - The human papillomavirus type 16/18 (HPV-16/18) AS04-adjuvanted cervical cancer
      vaccine is licensed for females aged 10 years and above and is therefore likely
      to be coadministered with other licensed vaccines, such as hepatitis B. In this
      randomized, open-label study, we compared the immunogenicity of the hepatitis B
      vaccine administered alone (HepB group) or with the HPV-16/18 AS04-adjuvanted
      vaccine (HepB+HPV group) in healthy women aged 20 to 25 years (clinical trial
      NCT00637195). The hepatitis B vaccine was given at 0, 1, 2, and 12 months (an
      accelerated schedule which may be required by women at high risk), and the HPV
      16/18 vaccine was given at 0, 1, and 6 months. One month after the third dose of
      hepatitis B vaccine, in the according-to-protocol cohort (n = 72 HepB+HPV; n = 76
      HepB), hepatitis B seroprotection rates (titer of >=10 mIU/ml) were 96.4% (95%
      confidence interval [CI], 87.5 to 99.6) and 96.9% (CI, 89.2 to 99.6) in the
      HepB+HPV and HepB groups, respectively, in women initially seronegative for anti
      hepatitis B surface antigen (HBs) and anti-hepatitis B core antigen (HBc).
      Corresponding geometric mean titers of anti-HBs antibodies were 60.2 mIU/ml (CI,
      40.0 to 90.5) and 71.3 mIU/ml (CI, 53.9 to 94.3). Anti-HBs antibody titers rose
      substantially after the fourth dose of hepatitis B vaccine. All women initially
      seronegative for anti-HPV-16 and anti-HPV-18 antibodies seroconverted after the
      second HPV-16/18 vaccine dose and remained seropositive up to 1 month after the
      third dose. Both vaccines were generally well tolerated, with no difference in
      reactogenicity between groups. In conclusion, coadministration of the HPV-16/18
      AS04-adjuvanted vaccine did not affect the immunogenicity or safety of the
      hepatitis B vaccine administered in an accelerated schedule in young women.

PMID- 21734064
TI  - Antibodies to lytic infection proteins in lymphocryptovirus-infected rhesus
      macaques: a model for humoral immune responses to epstein-barr virus infection.
AB  - Humoral immune responses to rhesus lymphocryptovirus (rhLCV) lytic infection
      proteins were evaluated in the rhesus macaque animal model for Epstein-Barr virus
      (EBV) infection. We found a hierarchy of humoral responses to 14 rhLCV lytic
      infection proteins in naturally infected rhesus macaques, with (i) widespread and
      robust responses to four glycoproteins expressed as late proteins, (ii) frequent
      but less robust responses to a subset of early proteins, and (iii) low-level
      responses to immediate-early proteins. This hierarchy of humoral responses was
      similar to that reported for EBV-infected humans, with the notable exception of
      the response to rhBARF1. Serum antibodies to rhBARF1 were frequently detected in
      healthy rhLCV-infected macaques, but in humans, anti-BARF1 antibodies have been
      reported primarily in patients with EBV-positive nasopharyngeal carcinoma (NPC).
      The macaque data accurately predicted that serum antibodies against BARF1 are a
      normal response to EBV infection when human serum samples are analyzed. The
      rhesus macaque animal provides a unique perspective on humoral responses to EBV
      infection in humans and can be a valuable model for EBV vaccine development.

PMID- 21734065
TI  - Mucosal immunization with a Staphylococcus aureus IsdA-cholera toxin A2/B chimera
      induces antigen-specific Th2-type responses in mice.
AB  - Staphylococcus aureus is a leading cause of opportunistic infection worldwide and
      a significant public health threat. The iron-regulated surface determinant A
      (IsdA) adhesin is essential for S. aureus colonization on human nasal epithelial
      cells and plays an important role in iron acquisition and resistance to human
      skin defenses. Here we investigated the murine immune response to intranasal
      administration of a cholera toxin A(2)/B (CTA(2)/B) chimera containing IsdA.
      Plasmids were constructed to express the IsdA-CTA(2)/B chimera and control
      proteins in Escherichia coli. Proper construction of the chimera was verified by
      SDS-PAGE, Western blotting, GM1 enzyme-linked immunosorbent assay (ELISA), and
      confocal microscopy. Groups of female BALB/c mice were mock immunized or
      immunized with IsdA-CTA(2)/B, IsdA mixed with CTA(2)/B, or IsdA alone, followed
      by one booster immunization at 10 days postpriming. Analysis of serum IgG and
      nasal, intestinal, and vaginal IgA suggested that mucosal immunization with IsdA
      CTA(2)/B induces significant IsdA-specific humoral immunity. Functional in vitro
      assays revealed that immune serum significantly blocks the adherence of S. aureus
      to human epithelial cells. Splenocytes from mice immunized with IsdA-CTA(2)/B
      showed specific cellular proliferation and production of interleukin-4 (IL-4)
      after in vitro stimulation. Immunization with IsdA-CTA(2)/B drove isotype
      switching to IgG1, indicative of a Th2-type response. Our results suggest that
      the immunogenicity of the S. aureus IsdA-CTA(2)/B chimera merits further
      investigation as a potential mucosal vaccine candidate.

PMID- 21734066
TI  - Reduced degranulation of NK cells in patients with frequently recurring herpes.
AB  - NK cells lyse virus-infected cells by degranulation; however, alterations in NK
      cell degranulation in persistent viral infections have not been directly studied.
      Earlier reports have documented a decrease in NK activity in patients with
      frequently recurring herpes (FRH). We corroborate these findings by showing that
      the degranulation responses of blood NK cells from patients with FRH, both during
      relapse and during remission, are significantly lower than those in healthy
      donors. The impaired degranulation was probably not caused by defective target
      cell recognition, since it was observed upon stimulation both with K562 cells and
      with a receptor-independent stimulus (phorbol 12-myristate 13-acetate plus
      ionomycin). We also show that the intracellular expression of perforin and CD107a
      by NK cells from patients with FRH is not different from that in healthy donors,
      thus excluding that the low NK cell degranulation in FRH is caused by a smaller
      size of the lytic granule compartment. We confirm previous reports on lowered NK
      activity in FRH patients and show that NK activity is significantly impaired only
      during remission, but not relapse; the causes for the discrepancy between the low
      degranulation and "normal" NK cell activity during relapse are discussed. In all,
      these data point at the deficit of NK cell degranulation in FRH. Whether this is
      a predisposing factor or a consequence of herpes simplex virus infection requires
      further investigation.

PMID- 21734067
TI  - Oral treatment of chickens with lactobacilli influences elicitation of immune
      responses.
AB  - Commensal microbes in the intestine are in constant interaction with host cells
      and play a role in shaping the immune system. Lactobacillus acidophilus,
      Lactobacillus reuteri, and Lactobacillus salivarius are members of the chicken
      intestinal microbiota and have been shown to induce different cytokine profiles
      in mononuclear cells in vitro. The objective of the present study was to examine
      the effects of these bacteria individually or in combination on the induction of
      antibody- and cell-mediated immune responses in vivo. The birds received
      lactobacilli weekly via oral gavage starting on day of hatch and subsequently, at
      14 and 21 days, were immunized with sheep red blood cells (SRBC), keyhole limpet
      hemocyanin (KLH), Newcastle disease virus vaccine, and infectious bursal disease
      virus vaccine. Antibody responses in serum were measured weekly for 4 weeks
      beginning on the day of primary immunization. The cell-mediated immune response
      was evaluated at 21 days postimmunization by measurement of gamma interferon (IFN
      gamma) production in splenocytes stimulated with inactivated vaccine antigens. L.
      salivarius-treated birds had significantly more serum antibody to SRBC and KLH
      than birds that were not treated with probiotics. L. salivarius-treated birds
      also had decreased cell-mediated immune responses to recall antigen stimulation.
      L. reuteri treatment did not significantly affect the systemic immune response,
      while L. acidophilus treatment increased the antibody response to KLH. These
      results indicate that systemic antibody- and cell-mediated immune responses can
      be modulated by oral treatment with lactobacilli but that these bacteria may vary
      in their ability to modulate the immune response.

PMID- 21734068
TI  - Monoclonal antibodies to hyphal exoantigens derived from the opportunistic
      pathogen Aspergillus terreus.
AB  - Aspergillus terreus has been difficult to identify in cases of aspergillosis, and
      clinical identification has been restricted to the broad identification of
      aspergillosis lesions in affected organs or the detection of fungal
      carbohydrates. As a result, there is a clinical need to identify species-specific
      biomarkers that can be used to detect invasive A. terreus disease. Monoclonal
      antibodies (MAbs) were developed to a partially purified preparation of cytolytic
      hyphal exoantigens (HEA) derived from A. terreus culture supernatant (CSN).
      Twenty-three IgG1 isotype murine MAbs were developed and tested for cross
      reactivity against hyphal extracts of 54 fungal species. Sixteen MAbs were shown
      to be specific for A. terreus. HEA were detected in conidia, hyphae, and in CSN
      of A. terreus. HEA were expressed in high levels in the hyphae during early
      stages of A. terreus growth at 37 degrees C, whereas at room temperature the
      expression of HEA peaked by days 4 to 5. Expression kinetics of HEA in CSN showed
      a lag, with peak levels at later time points at room temperature and 37 degrees C
      than in hyphal extracts. Serum spiking experiments demonstrated that human serum
      components do not inhibit detection of the HEA epitopes by MAb enzyme-linked
      immunosorbent assay (ELISA). Immunoprecipitation and proteomic analysis
      demonstrated that MAbs 13E11 and 12C4 immunoprecipitated a putative
      uncharacterized leucine aminopeptidase (Q0CAZ7), while MAb 19B2 recognized a
      putative dipeptidyl-peptidase V (DPP5). Studies using confocal laser scanning
      microscopy showed that the uncharacterized leucine aminopeptidase mostly
      localized to extracellular matrix structures while dipeptidyl-peptidase V was
      mostly confined to the cytoplasm.

PMID- 21734069
TI  - When might a cane be necessary for walking following a stroke?
AB  - BACKGROUND: For individuals with lateral postural imbalance after stroke, the
      decision to adopt a cane for walking often is not based on objective findings.
      OBJECTIVE: The authors investigated the explanatory value of 2 posturographic
      criteria for lateral postural imbalance on the walking abilities of poststroke
      subjects. METHODS: Indices of postural asymmetry (percentage of body weight on
      the less loaded lower limb) and instability (mediolateral variance of center-of
      pressure displacements) were measured in 40 healthy individuals and 52 patients
      (mean 94.2 days after first hemispheric stroke), who stood still on a double
      force platform. Cut-off values (mean +/- 2 standard deviations) were calculated
      and compared. The predictive value of both postural indices on walking abilities
      with or without a cane was analyzed. RESULTS: Of the patients, 34.6% were
      unstable along the mediolateral axis (variance >7 mm(2)), and 44.2% were
      asymmetrical (body weight <40%); 30% needed a technical aid and 35% walked
      without a cane. The probability of being able to walk without a cane was less
      than 5% if the paretic lower limb was not loaded more than 40%. The postural
      instability index was less informative. CONCLUSIONS: This study suggests that
      patients who do not load more than 40% of their body weight on their paretic
      lower limb may benefit from the prescription of a cane.

PMID- 21734070
TI  - Atrophy and intramuscular fat in specific muscles of the thigh: associated
      weakness and hyperinsulinemia in stroke survivors.
AB  - PURPOSE: Sarcopenia and increased fat infiltration in muscle may play a role in
      the functional impairment and high risk for diabetes in stroke. Our purpose was
      to compare muscle volume and muscle attenuation across 6 muscles of the paretic
      and nonparetic thigh and examine the relationships between intramuscular fat and
      insulin resistance and between muscle volume and strength in stroke patients.
      METHODS: Stroke participants (70; 39 men, 31 women) aged 40 to 84 years, BMI = 16
      to 45 kg/m(2) underwent multiple thigh CT scans, total body scan by DXA (dual
      energy X-ray absorptiometry), peak oxygen intake (VO(2peak)) graded treadmill
      test, 6-minute walk, fasting blood draws, and isokinetic strength testing.
      RESULTS: Muscle volume is 24% lower and subcutaneous fat volume is 5% higher in
      the paretic versus nonparetic thigh. Muscle attenuation (index of amount of fat
      infiltration in muscle) is 17% higher in the nonparetic midthigh than the
      paretic. The semitendinosis/semimembranosis, biceps femoris, sartorius, vastus
      (medialis/lateralis), and rectus femoris have lower (between 9% and 19%) muscle
      areas on the paretic than the nonparetic thigh. Muscle attenuation is 15% to 25%
      higher on the nonparetic than the paretic side for 5 of 6 muscles. The nonparetic
      midthigh muscle attenuation is negatively associated with insulin. Eccentric peak
      torque of the nonparetic leg and paretic leg are associated with the
      corresponding muscle volume. CONCLUSIONS: The skeletal muscle atrophy, increased
      fat around and within muscle, and ensuing muscular weakness observed in chronic
      stroke patients relates to diabetes risk and may impair functional mobility and
      independence.

PMID- 21734071
TI  - Changes in breast cancer biomarkers in the IGF1R/PI3K pathway in recurrent breast
      cancer after tamoxifen treatment.
AB  - Development of resistance to the antioestrogen tamoxifen occurs in a large
      proportion of patients with oestrogen receptor-positive (ER+) breast cancer and
      is an important clinical challenge. While loss of ER occurs in c.20% of tamoxifen
      resistant tumours, this cannot be the sole explanation for tamoxifen treatment
      failure. PI3K pathway activation, including by insulin-like growth factor
      receptor 1 (IGF1R), has been implicated in some resistance models. The primary
      aim was to determine whether evidence exists in clinical breast cancer for a role
      of IGF1R and/or the PI3K pathway, in acquisition of resistance to tamoxifen.
      Invasive primary and recurrent tamoxifen-resistant tumours from the same patient
      (n=77) were assessed for changes in ER, progesterone receptor (PgR), human
      epidermal growth factor receptor 2 (HER2), IGF1R, stathmin, PTEN expression and
      PIK3CA mutations where possible. ER and PgR levels were significantly reduced at
      recurrence with 22 and 45%, respectively, showing negative status at this time.
      Acquisition of HER2 overexpression occurred in 6% of cases. IGF1R expression was
      significantly reduced in both ER+ and ER- recurrences and stathmin levels
      increased. A positive association between stathmin and IGF1R emerged in recurrent
      samples, despite their opposing relationships with ER, suggesting some
      coalescence of their activities may be acquired. The data confirm loss of ER and
      PgR and gain of HER2 in some tamoxifen-resistant tumours. There is no evidence
      for IGF1R gain in tamoxifen resistance; increases in stathmin levels suggest that
      activation of the PI3K pathway may have contributed, but PTEN loss and PIK3CA
      hotspot mutations were relatively rare.

PMID- 21734072
TI  - Insulinoma-released exosomes or microparticles are immunostimulatory and can
      activate autoreactive T cells spontaneously developed in nonobese diabetic mice.
AB  - Exosomes (EXO) are secreted intracellular microparticles that can trigger
      inflammation and induce Ag-specific immune responses. To test possible roles of
      EXO in autoimmunity, we isolated small microparticles, mainly EXO, from mouse
      insulinoma and examined their activities to stimulate the autoimmune responses in
      NOD mice, a model for human type 1 diabetes. We demonstrate that the EXO contains
      strong innate stimuli and expresses candidate diabetes autoantigens. They can
      induce secretion of inflammatory cytokines through a MyD88-dependent pathway, and
      activate purified APC and result in T cell proliferation. To address whether EXO
      or the secreted microparticles are possible autoimmune targets causing islet
      specific inflammation, we monitored the T cell responses spontaneously developed
      in prediabetic NOD mice for their reactivity to the EXO, and compared this
      reactivity between diabetes-susceptible and -resistant congenic mouse strains. We
      found that older NOD females, which have advanced islet destruction, accumulated
      more EXO-reactive, IFN-gamma-producing lymphocytes than younger females or age
      matched males, and that pancreatic lymph nodes from the prediabetic NOD, but not
      from the resistant mice, were also enriched with EXO-reactive Th1 cells. In vivo,
      immunization with the EXO accelerates insulitis development in nonobese diabetes
      resistant mice. Thus, EXO or small microparticles can be recognized by the
      diabetes-associated autoreactive T cells, supporting that EXO might be a possible
      autoimmune target and/or insulitis trigger in NOD or congenic mouse strains.

PMID- 21734073
TI  - TNF receptor 1 deficiency increases regulatory T cell function in nonobese
      diabetic mice.
AB  - TNF has been implicated in the pathogenesis of type 1 diabetes. When administered
      early in life, TNF accelerates and increases diabetes in NOD mice. However, when
      administered late, TNF decreases diabetes incidence and delays onset. TNFR1
      deficient NOD mice were fully protected from diabetes and only showed mild peri
      insulitis. To further dissect how TNFR1 deficiency affects type 1 diabetes, these
      mice were crossed to beta cell-specific, highly diabetogenic TCR transgenic I
      A(g7)-restricted NOD4.1 mice and Kd-restricted NOD8.3 mice. TNFR1-deficient
      NOD4.1 and NOD8.3 mice were protected from diabetes and had significantly less
      insulitis compared with wild type NOD4.1 and NOD8.3 controls. Diabetic NOD4.1
      mice rejected TNFR1-deficient islet grafts as efficiently as control islets,
      confirming that TNFR1 signaling is not directly required for beta cell
      destruction. Flow cytometric analysis showed a significant increase in the number
      of CD4(+)CD25(+)Foxp3(+) T regulatory cells in TNFR1-deficient mice. TNFR1
      deficient T regulatory cells were functionally better at suppressing effector
      cells than were wild type T regulatory cells both in vitro and in vivo. This
      study suggests that blocking TNF signaling may be beneficial in increasing the
      function of T regulatory cells and suppression of type 1 diabetes.

PMID- 21734074
TI  - The dual function cytokine IL-33 interacts with the transcription factor NF
      kappaB to dampen NF-kappaB-stimulated gene transcription.
AB  - Full-length IL-33 is a member of the IL-1 family of cytokines, which can act in
      an autocrine or paracrine manner by binding to the IL-33R on several different
      target cell types. In addition, IL-33 can act in an intracrine fashion by
      translocating to the nucleus, where it binds to the chromatin and modulates gene
      expression. In this article, we report that full-length IL-33, but not mature IL
      33, interacts with the transcription factor NF-kappaB. This interaction occurs
      between the N-terminal part of IL-33 from aa 66-109 and the N-terminal Rel
      homology domain of NF-kappaB p65. Coimmunoprecipitation experiments in cells
      overexpressing IL-33 or endogenously expressing IL-33 revealed rhIL-1beta
      stimulated association between IL-33 and p65, whereas binding to the p50 subunit
      was constitutive. The biological consequence of IL-33/NF-kappaB complex formation
      was reduction in NF-kappaB p65 binding to its cognate DNA and impairment of p65
      triggered transactivation. Overexpression of IL-33 resulted in a reduction and
      delay in the rhIL-1beta-stimulated expression of endogenous NF-kappaB target
      genes such as IkappaBalpha, TNF-alpha, and C-REL. We suggest that nuclear IL-33
      sequesters nuclear NF-kappaB and reduces NF-kappaB-triggered gene expression to
      dampen proinflammatory signaling.

PMID- 21734075
TI  - NF-kappaB signaling participates in both RANKL- and IL-4-induced macrophage
      fusion: receptor cross-talk leads to alterations in NF-kappaB pathways.
AB  - NF-kappaB activation is essential for receptor activator for NF-kappaB ligand
      (RANKL)-induced osteoclast formation. IL-4 is known to inhibit the RANKL-induced
      osteoclast differentiation while at the same time promoting macrophage fusion to
      form multinucleated giant cells (MNG). Several groups have proposed that IL-4
      inhibition of osteoclastogenesis is mediated by suppressing the RANKL-induced
      activation of NF-kappaB. However, we found that IL-4 did not block proximal,
      canonical NF-kappaB signaling. Instead, we found that IL-4 inhibited alternative
      NF-kappaB signaling and induced p105/50 expression. Interestingly, in nfkappab1(
      /-) bone marrow-derived macrophages (BMM), the formation of both multinucleated
      osteoclast and MNG induced by RANKL or IL-4, respectively, was impaired. This
      suggests that NF-kappaB signaling also plays an important role in IL-4-induced
      macrophage fusion. Indeed, we found that the RANKL-induced and IL-4-induced
      macrophage fusion were both inhibited by the NF-kappaB inhibitors IkappaB kinase
      2 inhibitor and NF-kappaB essential modulator inhibitory peptide. Furthermore,
      overexpression of p50, p65, p52, and RelB individually in nfkappab1(-/-) or
      nfkappab1(+/+) BMM enhanced both giant osteoclast and MNG formation.
      Interestingly, knockdown of nfkappab2 in wild-type BMM dramatically enhanced both
      osteoclast and MNG formation. In addition, both RANKL- and IL-4-induced
      macrophage fusion were impaired in NF-kappaB-inducing kinase(-/-) BMM. These
      results suggest IL-4 influences NF-kappaB pathways by increasing p105/p50 and
      suppressing RANKL-induced p52 translocation and that NF-kappaB pathways
      participate in both RANKL- and IL-4-induced giant cell formation.

PMID- 21734076
TI  - CD31 is required on CD4+ T cells to promote T cell survival during Salmonella
      infection.
AB  - Hematopoietic cells constitutively express CD31/PECAM1, a signaling adhesion
      receptor associated with controlling responses to inflammatory stimuli. Although
      expressed on CD4(+) T cells, its function on these cells is unclear. To address
      this, we have used a model of systemic Salmonella infection that induces high
      levels of T cell activation and depends on CD4(+) T cells for resolution.
      Infection of CD31-deficient (CD31KO) mice demonstrates that these mice fail to
      control infection effectively. During infection, CD31KO mice have diminished
      numbers of total CD4(+) T cells and IFN-gamma-secreting Th1 cells. This is
      despite a higher proportion of CD31KO CD4(+) T cells exhibiting an activated
      phenotype and an undiminished capacity to prime normally and polarize to Th1.
      Reduced numbers of T cells reflected the increased propensity of naive and
      activated CD31KO T cells to undergo apoptosis postinfection compared with wild
      type T cells. Using adoptive transfer experiments, we show that loss of CD31 on
      CD4(+) T cells alone is sufficient to account for the defective CD31KO T cell
      accumulation. These data are consistent with CD31 helping to control T cell
      activation, because in its absence, T cells have a greater propensity to become
      activated, resulting in increased susceptibility to become apoptotic. The impact
      of CD31 loss on T cell homeostasis becomes most pronounced during severe,
      inflammatory, and immunological stresses such as those caused by systemic
      Salmonella infection. This identifies a novel role for CD31 in regulating CD4 T
      cell homeostasis.

PMID- 21734078
TI  - Comment on "Dermatitis herpetiformis sera or goat anti-transglutaminase-3
      transferred to human skin-grafted mice mimics dermatitis herpetiformis
      immunopathology".

PMID- 21734077
TI  - Prevention of lymphocyte apoptosis in septic mice with cancer increases
      mortality.
AB  - Lymphocyte apoptosis is thought to have a major role in the pathophysiology of
      sepsis. However, there is a disconnect between animal models of sepsis and
      patients with the disease, because the former use subjects that were healthy
      prior to the onset of infection while most patients have underlying
      comorbidities. The purpose of this study was to determine whether lymphocyte
      apoptosis prevention is effective in preventing mortality in septic mice with
      preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild
      type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell
      line. Three weeks later, after development of palpable tumors, all animals
      received an intratracheal injection of Pseudomonas aeruginosa. Despite having
      decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly
      increased mortality compared with WT mice following P. aeruginosa pneumonia (85
      versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was
      associated with increases in Th1 cytokines TNF-alpha and IFN-gamma in
      bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10
      in stimulated splenocytes. There were no differences in tumor size or pulmonary
      pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference
      was not specific to Bcl-2 overexpression, similar experiments were performed in
      Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality
      compared with septic WT mice with cancer. These data demonstrate that, despite
      overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in
      septic hosts without comorbidities, the same strategy worsens survival in mice
      with cancer that are given pneumonia.

PMID- 21734079
TI  - Modulation of inflammasome pathways by bacterial and viral pathogens.
AB  - Inflammasomes are emerging as key regulators of the host response against
      microbial pathogens. These cytosolic multiprotein complexes recruit and activate
      the cysteine protease caspase-1 when microbes invade sterile tissues or elicit
      cellular damage. Inflammasome-activated caspase-1 induces inflammation by
      cleaving the proinflammatory cytokines IL-1beta and IL-18 into their biologically
      active forms and by releasing the alarmin HMGB1 into the extracellular milieu.
      Additionally, inflammasomes counter bacterial replication and clear infected
      immune cells through an inflammatory cell death program termed pyroptosis. As a
      countermeasure, bacterial and viral pathogens evolved virulence factors to
      antagonize inflammasome pathways. In this review, we discuss recent progress on
      how inflammasomes contribute to host defense against bacterial and viral
      pathogens, and we review how viruses and bacteria modulate inflammasome function
      to their benefit.

PMID- 21734080
TI  - Circulating micro-RNAs in acute kidney injury: early observations.

PMID- 21734081
TI  - Assessment of glycemic control in dialysis patients with diabetes: glycosylated
      hemoglobin or glycated albumin?

PMID- 21734082
TI  - Comparison of insulin action on glucose versus potassium uptake in humans.
AB  - BACKGROUND AND OBJECTIVES: Insulin has several physiologic actions that include
      stimulation of cellular glucose and potassium uptake. The ability of insulin to
      induce glucose uptake by cells is impaired in type 2 diabetes mellitus, but
      whether potassium uptake is similarly impaired is not known. This study examines
      whether the cellular uptake of these molecules is regulated in concert or
      independently. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty-two
      nondiabetic and 13 type 2 diabetic subjects with normal GFR were given a similar,
      constant metabolic diet for 8 days. On day 9, they were subjected to a
      hyperinsulinemic euglycemic clamp for 2 hours. Serum and urinary chemistry were
      obtained before and during the clamp. Glucose disposal rate was calculated from
      glucose infusion rate during hyperinsulinemic euglycemia. Intracellular potassium
      and phosphate uptake were calculated by the reduction of extracellular potassium
      or phosphate content corrected for urinary excretion. RESULTS: Although glucose
      disposal rate tended to be lower in type 2 diabetics, cellular potassium uptake
      was similar between diabetics and nondiabetics. Additionally, although glucose
      disposal rate was lower with increasing body mass index (R2 = 0.362), cellular
      potassium (R2 = 0.052), and phosphate (R2 = 0.002), uptake rates did not
      correlate with body mass index. There was also no correlation between glucose
      disposal rate and potassium (R2 = 0.016) or phosphate uptake (R2 = 0.053).
      Conclusions Insulin-stimulated intracellular uptake of glucose and potassium are
      independent of each other. In type 2 diabetes, potassium uptake is preserved
      despite impaired glucose disposal.

PMID- 21734083
TI  - Endogenous erythropoietin and the association with inflammation and mortality in
      diabetic chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Anemia and inflammation are prevalent in diabetic
      patients with chronic kidney disease (CKD). The role of endogenous erythropoietin
      (EPO) in the pathophysiology of anemia in chronic diseases and its relationship
      to clinical outcomes remain uncertain. In this cohort study, we aimed to identify
      factors associated with endogenous EPO levels and investigate their relation to
      all-cause mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between 2004
      and 2005, 215 patients with type 2 diabetes were enrolled. Exclusion criteria
      included stage renal disease ESRD and any form of anemia therapy. The association
      of EPO levels with clinical and laboratory variables was investigated by linear
      regression modeling. Predictors of all-cause mortality were evaluated by Cox
      proportional hazards analyses. RESULTS: Patients (median age, 67 years; 52% men;
      median duration of diabetes, 10 years; median estimated GFR, 49 ml/min per 1.73
      m2) were followed for up to 7.0 years. Forty-one patients died. Elevated EPO
      levels were independently associated with elevated C-reactive protein, low
      ferritin, and hypertension, in a multivariate model that also included age,
      cardiovascular disease, kidney function, albumin, cholesterol, and hemoglobin.
      Higher EPO levels were independently predictive for mortality, as were age, low
      levels of albumin, and cardiovascular disease. CONCLUSIONS: In diabetic patients
      with CKD, elevated endogenous EPO levels were predictive for mortality and were
      related mainly to markers of inflammation, independent of kidney function, and
      despite low hemoglobin levels. Understanding the phenomenon of EPO resistance and
      iron dysregulation caused by inflammation is crucial for effective and safe
      treatment of anemia in patients with CKD.

PMID- 21734084
TI  - TRPC6 mutations in children with steroid-resistant nephrotic syndrome and
      atypical phenotype.
AB  - BACKGROUND AND OBJECTIVES: Mutations in the TRPC6 gene have been recently
      identified as the cause of late-onset autosomal-dominant focal segmental
      glomerulosclerosis (FSGS). To extend the screening, we analyzed TRPC6 in 33
      Italian children with sporadic early-onset SRNS and three Italian families with
      adult-onset FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: TRPC6 mutation
      analysis was performed through PCR and sequencing. The effects of the detected
      amino acid substitutions were analyzed by bioinformatics tools and functional in
      vitro studies. The expression levels of TRPC6 and nephrin proteins were evaluated
      by confocal microscopy. RESULTS: Three heterozygous missense mutations
      (c.374A>G_p.N125S, c.653A>T_p.H218L, c.2684G>T_p.R895L) were identified. The
      first new mutation, p.H218L, was found in a 18-year-old boy who presented a
      severe form of FSGS at the age of 8 years. The second, p.R895L, a new de novo
      mutation, was identified in a girl with collapsing glomerulosclerosis at the age
      of 2 years. The former mutation, p.N125S, was found in two siblings with early
      onset steroid-resistant nephrotic syndrome (SRNS) at the ages of 4 and 14 years.
      Renal immunofluorescence revealed upregulated expression of TRPC6 and loss of
      nephrin in glomeruli. The intracellular calcium concentrations were significantly
      higher in the cells expressing all mutant TRPC6 channels compared with cells
      expressing wild-type TRPC6. CONCLUSIONS: Our findings suggest that TRPC6 variants
      can also be detected in children with early-onset and sporadic SRNS (4 of 33
      patients). Moreover, in one patient a new de novo TRPC6 mutation was associated
      with a rare severe form of childhood collapsing glomerulosclerosis with rapid
      progression to uremia.

PMID- 21734085
TI  - Clinical practices and outcomes in elderly hemodialysis patients: results from
      the Dialysis Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND AND OBJECTIVES: Demand for hemodialysis among elderly patients is
      increasing worldwide. Although clinical care of this high-risk group is complex
      and challenging, no guidelines exist to inform hemodialysis practices. The
      Dialysis Outcomes and Practice Patterns Study (DOPPS) provides a unique
      opportunity to assess dialysis practices and associated outcomes among elderly
      versus younger patients on chronic in-center hemodialysis in 12 countries.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical characteristics, dialysis
      practices, and outcomes of elderly versus younger patients were compared among
      participants in four DOPPS regions in 2005 through 2007. RESULTS: Although
      participant mean age increased over time in all DOPPS countries, the percentage
      of elderly varied widely. Overall, comorbidities and malnutrition were more
      common in the elderly. Fistulae were used less frequently among elderly versus
      younger patients in Europe and North America but not in Australia, New Zealand,
      and Japan. No difference in treatment time was observed between elderly and
      younger patients after normalizing for body weight. In all regions,
      ultrafiltration rates were lower among elderly patients. Elderly patients
      reported poorer quality of life with respect to the physical but not mental
      component scores. Mortality risk was three- to sixfold higher in the elderly
      group, whereas causes of death overall were similar for elderly and younger
      patients. CONCLUSIONS: Elderly patients represent a different proportion of DOPPS
      participants across countries, possibly reflecting differences in policies and
      clinical practices. In general, hemodialysis practices in the elderly reflected
      each region's clinical patterns, with some variation by age group depending upon
      the practice.

PMID- 21734086
TI  - Longitudinal body composition changes due to dialysis.
AB  - BACKGROUND AND OBJECTIVES: Nutritional status remains a powerful predictor of
      outcome in the dialysis population. High body mass index (BMI) seems protective,
      but which body compartment (fat or lean mass) confers this protection remains
      unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a longitudinal
      study (n = 60; n = 46 completed) examining changes in body composition in
      incident peritoneal dialysis (PD) and hemodialysis (HD) patients over 12 months.
      We measured total body protein (TBP) by in vivo neutron activation, expressed as
      nitrogen index (NI), and lean body mass (LBM) and total body fat (TBF) by dual
      energy x-ray absorptiometry. Visceral and subcutaneous fat areas (SFAs) were
      determined from computed tomography. Comparisons were made between different BMI
      groups and dialysis modalities. RESULTS: No significant change was found in TBP,
      NI, or TBF. The obese group (BMI >30) had an increase in all mean LBM parameters
      with a significant increase in NI compared with normal-weight and the overweight
      group. This increase in NI remained significant after multivariate analysis beta
      coefficient (0.08). PD patients had the greatest increase in TBF, with a
      significant increase in visceral fat (VFA:SFA ratio beta coefficient = 0.23).
      CONCLUSIONS: Obese patients showed preservation of TBP compared with normal- and
      overweight patients, suggesting that energy storage as fat mass is of value in
      the dialysis population.

PMID- 21734087
TI  - Intradialytic hypertension and the association with interdialytic ambulatory
      blood pressure.
AB  - BACKGROUND AND OBJECTIVES: Increasing BP during maintenance hemodialysis or
      intradialytic hypertension is associated with increased morbidity and mortality.
      In hemodialysis patients, ambulatory BP measurements predict adverse
      cardiovascular outcomes better than in-center measurements. We hypothesized that
      patients with intradialytic hypertension have higher interdialytic ambulatory
      systolic BP than those without intradialytic hypertension. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We performed a case-control study in adult
      hemodialysis patients. Cases consisted of subjects with intradialytic
      hypertension (systolic BP increase >=10 mmHg from pre- to posthemodialysis in at
      least four of six treatments), and controls were subjects with >=10 mmHg
      decreases from pre- to posthemodialysis in at least four of six treatments. The
      primary outcome was mean interdialytic 44-hour systolic ambulatory BP. RESULTS:
      Fifty subjects with a mean age of 54.5 years were enrolled (25 per group) among
      whom 80% were men, 86% diabetic, 62% Hispanic, and 38% African American. The mean
      prehemodialysis systolic BP for the intradialytic-hypertension and control groups
      were 144.0 and 155.5 mmHg, respectively. Mean posthemodialysis systolic BP was
      159.0 and 128.1 mmHg, for the intradialytic-hypertension and control groups,
      respectively. The mean systolic ambulatory BP was 155.4 and 142.4 mmHg for the
      intradialytic-hypertension and control groups, respectively (P = 0.005). Both
      daytime and nocturnal systolic BP were higher among those with intradialytic
      hypertension as compared with controls. There was no difference in interdialytic
      weight gain between groups. CONCLUSIONS: Time-integrated BP burden as measured by
      44-hour ambulatory BP is higher in hemodialysis patients with intradialytic
      hypertension than those without intradialytic hypertension.

PMID- 21734088
TI  - Cardiovascular and noncardiovascular mortality among men and women starting
      dialysis.
AB  - BACKGROUND AND OBJECTIVES: Although women have a survival advantage in the
      general population, women on dialysis have similar mortality to men. We
      hypothesized that this paired mortality risk during dialysis may be explained by
      a relative excess of cardiovascular-related mortality in women. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We compared 5-year age-stratified cardiovascular
      and noncardiovascular mortality rates, relative risks, and hazard ratios in a
      European cohort of incident adult dialysis patients (European Renal Association
      European Dialysis and Transplant Association [ERA-EDTA] Registry) with the
      European general population (Eurostat). Cause of death was recorded by ERA-EDTA
      codes in dialysis patients and by International Statistical Classification of
      Diseases codes in the general population. RESULTS: Overall, sex did not have a
      predictive effect on outcome in dialysis. Stratification into age categories and
      causes of death showed greater noncardiovascular mortality in young women (<45
      years). In other age categories (45 to 55 and >55 years), women presented lower
      cardiovascular mortality. This cardiovascular benefit was, however, smaller than
      in the general population. Stratification by diabetic nephropathy showed that
      diabetic women in all age categories remained at increased mortality risk
      compared with men, an effect mainly attributed to the noncardiovascular
      component. CONCLUSIONS: Mortality rates and causes of death in men and women on
      dialysis vary with age. Increased noncardiovascular mortality may explain the
      loss of the survival advantage of women on dialysis. Both young and diabetic
      women starting dialysis are at a higher mortality risk than equal men.

PMID- 21734089
TI  - Development and validation of a general population renal risk score.
AB  - BACKGROUND AND OBJECTIVES: There is a need for prediction scores that identify
      individuals at increased risk for developing progressive chronic kidney disease
      (CKD). Therefore, this study was performed to develop and validate a "renal risk
      score" for the general population. Design, setting, participants, & measurements
      For this study we used data from the PREVEND (Prevention of Renal and Vascular
      ENdstage Disease) study, a prospective population-based cohort study with a
      median follow-up of 6.4 years. Participants with two or three consecutive
      estimated GFR (eGFR) measurements during follow-up were included. Participants
      within the group who had the most renal function decline (top 20% of the total
      population) and had an eGFR value <60 ml/min per 1.73 m2 during follow-up were
      defined as having progressive CKD. Possible predictors for progressive CKD were
      selected on the basis of univariable logistic regression analyses. RESULTS: A
      final prediction model was built using backward logistic regression analysis.
      Besides baseline eGFR, the model contained age, urinary albumin excretion,
      systolic BP, C-reactive protein, and known hypertension. The area under the
      receiver operating characteristic (ROC) curve was 0.84. We performed internal
      validation by using a bootstrapping procedure. As expected, after the regression
      coefficients were corrected for optimism, the area under the ROC curve was still
      0.84. For clinical use we divided all predictors in meaningful clinical
      categories to develop a score chart. The area under the ROC curve was 0.83,
      indicating the high discriminative value of this model. CONCLUSIONS: Given the
      high internal validity of this renal risk score, this score can be helpful to
      identify individuals at increased risk for progressive CKD.

PMID- 21734090
TI  - Predictors of acute kidney injury in septic shock patients: an observational
      cohort study.
AB  - BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is a frequent complication
      in critically ill patients and sepsis is the most common contributing factor. We
      aimed to determine the risk factors associated with AKI development in patients
      with septic shock. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Observational
      cohort study consisted of consecutive adults with septic shock admitted to a
      medical intensive care unit (ICU) of a tertiary care academic hospital from July
      2005 to September 2007. AKI was defined according to RIFLE criteria (urine output
      and creatinine criteria). Demographic, clinical, and treatment variables were
      reviewed. Main outcomes measured were AKI occurrence, all-cause hospital
      mortality, and hospital and ICU length of stay. RESULTS: Three hundred ninety
      patients met inclusion criteria, of which 237 (61%) developed AKI. AKI
      development was independently associated with delay to initiation of adequate
      antibiotics, intra-abdominal sepsis, blood product transfusion, use of
      angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker, and body
      mass index (kg/m2). Higher baseline GFR and successful early goal directed
      resuscitation were associated with a decreased risk of AKI. Hospital mortality
      was significantly greater in patients who developed AKI (49 versus 34%).
      CONCLUSIONS: In a contemporary cohort of patients with septic shock, both patient
      and health care delivery risk factors seemed to be important for AKI development.

PMID- 21734091
TI  - Recurrence and graft loss after kidney transplantation for henoch-schonlein
      purpura nephritis: a multicenter analysis.
AB  - BACKGROUND AND OBJECTIVES: The actuarial risk at 5 years for clinical recurrence
      of Henoch-Schonlein purpura nephritis (HSPN) and graft loss caused by recurrence
      of -HSPN after renal transplantation was reported in 1994 to be as high as 35%
      and 11%, respectively. The aim of this study is to re-evaluate, in a large cohort
      of patients with a long-term follow-up, whether these rates have changed. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from six transplant centers in
      Belgium and France with strict diagnostic criteria of HSPN and a potential post
      transplant follow-up of >=3 years were included. RESULTS: Forty-three patients
      were included. Patient survival is excellent: 98%, 95%, and 95% at 5, 10, and 15
      years, respectively. Overall graft survival rates were 84%, 66%, and 56% at 5,
      10, and 15 years, respectively. Clinical recurrence in a first kidney transplant
      occurred in five patients. Three patients lost their first graft due to HSPN
      recurrence 19 to 96 months after transplantation, two of whom had systemic signs
      of the illness. Actuarial risk for clinical recurrence in a first graft is 2.5%
      and 11.5% at 5 and 10 years, respectively. Actuarial risk for graft loss caused
      by recurrence in a first graft is 2.5% and 7.5% at 5 and 10 years, respectively.
      Severity of the disease at presentation and type of immunosuppression after
      transplantation did not affect recurrence. CONCLUSIONS: We found that recurrence
      rates of HSPN after transplantation are lower than previously reported. The
      actuarial risk of graft loss from recurrence in a first graft is 7.5% at 10
      years.

PMID- 21734092
TI  - Introduction to the well-transplant visit--more than vital signs and a creatinine
      check.

PMID- 21734093
TI  - Monitoring and managing graft health in the kidney transplant recipient.
AB  - Ongoing monitoring of kidney transplants is a widely accepted and practiced part
      of posttransplantation management. One reason to monitor is to evaluate whether
      the transplant is stable. The transplant community evaluates stability by
      checking kidney function. Despite problems with sensitivity and specificity,
      obtaining serial serum creatinine levels is the most common approach to assessing
      kidney function. Some programs supplement serial serum creatinine levels with
      surveillance kidney biopsies. Although not uniformly accepted as beneficial,
      surveillance biopsies are useful in select subsets of patients such as highly
      sensitized recipients. Recent biopsy studies shed light on which histopathology
      findings portend poor prognoses. The Long-Term Deterioration of Kidney Allograft
      Function Study (DeKAF) and similar studies that will prospectively evaluate
      therapeutic interventions should help the transplant community better define how
      to monitor and manage the kidney transplant optimally. In the meantime, Kidney
      Diseases: Improving Global Outcomes (KDIGO) provides an evidence-based approach
      toward monitoring and managing the kidney transplant.

PMID- 21734094
TI  - Metabolic syndrome in kidney transplantation: management of risk factors.
AB  - The metabolic syndrome is a constellation of clinical abnormalities related to
      insulin resistance and inflammation. The syndrome is now recognized as a risk
      factor for diabetes and cardiovascular disease in the general population. Recent
      studies suggest that the metabolic syndrome is common after kidney
      transplantation, also possibly being predictive of allograft loss and poor
      allograft function. The development or worsening of obesity plays a central role
      in the development of metabolic syndrome after kidney transplantation.
      Immunosuppression also plays an important role in the pathogenesis of the
      individual components of the metabolic syndrome. In fact, the overriding
      influence of immunosuppressive medications makes it unclear whether the metabolic
      syndrome has the same value in predicting outcomes as is true in the general
      population. However, recent studies suggest that the presence of metabolic
      syndrome before transplantation predicts the subsequent development of new-onset
      diabetes after transplantation, independent of other widely known risk factors.
      Aggressive management of the metabolic syndrome is warranted both before and
      after transplantation.

PMID- 21734095
TI  - Posttransplantation proteinuria: an approach to diagnosis and management.
AB  - Proteinuria is a common problem encountered in the treatment of renal transplant
      recipients, occurring in up to 45% of patients. Proteinuria from native kidneys
      falls rapidly after renal transplantation, and persistent or worsening
      proteinuria is usually indicative of allograft pathology. Biopsy studies of
      transplant patients with proteinuria have confirmed that transplant-specific
      diagnoses (transplant glomerulopathy, interstitial fibrosis and tubular atrophy,
      and acute rejection) are more commonly found than other proteinuric conditions,
      such as glomerulonephritis. As in the nontransplant setting, proteinuria is
      associated with worse clinical outcomes, including an increased risk for death,
      cardiovascular events, and graft loss. Blockade of the renin-angiotensin
      aldosterone system with angiotensin-converting enzyme inhibitors and angiotensin
      receptor blockers will reduce proteinuria, but the long-term effect of these
      medications on patient and graft survival remains unknown.

PMID- 21734096
TI  - Posttransplantation anemia: mechanisms and management.
AB  - Treatment of anemia in patients with chronic kidney disease is a topic of
      increasing interest and controversy. However, anemia in the kidney transplant
      recipient has received relatively little attention in the literature despite the
      reported high prevalence of 30% to 40%. The pathogenesis of anemia among kidney
      transplant recipients is usually multifactorial, including compromised graft
      function, iron deficiency, immunosuppressive and other medications, and an
      inflammatory state causing erythropoietin resistance. It is unclear whether
      posttransplantation anemia is causally linked to cardiovascular events and
      mortality. Clinicians should screen kidney transplant recipients for
      posttransplantation anemia and carefully weigh the potential risks and benefits
      of treatment on an individual basis until well-designed, prospective studies
      provide further insight. This article reviews the prevalence, pathogenesis, and
      management of anemia in kidney transplant recipients.

PMID- 21734097
TI  - Downregulation of Klotho expression by dehydration.
AB  - Klotho, a transmembrane protein, protease, and hormone mainly expressed in renal
      tissue counteracts aging. Overexpression of Klotho substantially prolongs the
      life span. Klotho deficiency leads to excessive formation of 1,25(OH)(2)D(3),
      growth deficit, accelerated aging, and early death. Aging is frequently
      paralleled by dehydration, which is considered to accelerate the development of
      age-related disorders. The present study explored the possibility that
      dehydration influences Klotho expression. Klotho transcript levels were
      determined by RT-PCR, and Klotho protein abundance was detected by Western
      blotting in renal tissue from hydrated and 36-h-dehydrated mice as well as in
      human embryonic kidney (HEK293) cells. Dehydration was followed by a significant
      decline of renal Klotho transcript levels and protein abundance, accompanied by
      an increase in plasma osmolarity as well as plasma ADH, aldosterone, and
      1,25(OH)(2)D(3) levels. Antidiuretic hormone (ADH; 50 nM) and aldosterone (1 MUM)
      significantly decreased Klotho transcription and protein expression in HEK293
      cells. In conclusion, the present observations disclose a powerful effect of
      dehydration on Klotho expression, an effect at least partially mediated by
      enhanced release of ADH and aldosterone.

PMID- 21734098
TI  - Advanced glycation end products inhibit adhesion ability of differentiated
      podocytes in a neuropilin-1-dependent manner.
AB  - Podocyte injury can occur by a number of stimuli. Maintaining of an intact
      podocyte structure is essential for glomerular filtration; therefore, podocyte
      damage severely impairs renal function. Recently, we have reported that addition
      of glycated BSA [advanced glycation end products (AGE)-BSA] to differentiated
      murine podocytes inhibited neuropilin-1 (NRP1) expression and dramatically
      influenced podocyte migration ability (Bondeva T, Ruster C, Franke S,
      Hammerschmid E, Klagsbrun M, Cohen CD, Wolf G. Kidney Int 75: 605-616, 2009;
      Bondeva T, Wolf G. Am J Nephrol 30: 336-345, 2009). The present study analyzes
      the influence of AGEs and NRP1 on podocyte adhesion and cytoskeleton
      reorganization. We show that treatment with AGE-BSA significantly reduced
      podocyte adhesion to collagen IV, laminin, and fibronectin compared with Co-BSA
      (nonglycated BSA)-incubated cells, which was further augmented by transient
      inhibition of NRP1 expression using NRP1 short interference (si) RNA. On the
      other hand, forced overexpression of NRP1 markedly increased the adhesion ability
      of podocytes to the ECMs despite the AGE-BSA treatment. No changes were observed
      when podocyte adhesion to collagen I was assayed. These findings were also
      manifested with disorganization of podocyte actin stress fibers and decreased
      lamellipodia formation processes due to AGE-BSA treatment or NRP1 suppression. In
      addition, AGE-BSA or suppression of NRP1 both reduced the phosphorylation of
      focal adhesion kinase (FAK) and Erk1/2 in PMA-stimulated differentiated
      podocytes. Analysis of RhoA family GTPase activity demonstrated that treatment
      with AGE-BSA or NRP1 depletion inhibited as well the activation of the Rac-1 and
      Cdc42 but did not affect RhoA activity. All these effects were reversed by forced
      overexpression of full-length NRP1 cloned into the pcDNA3 vector in
      differentiated podocytes. Our study demonstrates that AGEs, in part via
      suppression of NRP1 expression, decreased podocyte adhesion and contribute to
      reduction of Rac-1 and Cdc42 GTPase activity. These effects may be further
      responsible for the podocytes damage and loss in diabetic nephropathy. Our
      findings suggest a role for NRP1 in regulating the podocyte actin cytoskeleton,
      and therefore reduction of NRP1 expression could be critical for podocyte
      function.

PMID- 21734099
TI  - E3 ubiquitin-protein ligases in rat kidney collecting duct: response to
      vasopressin stimulation and withdrawal.
AB  - The E3 ubiquitin (Ub)-protein ligases (E3s) play a role as regulators of protein
      trafficking and degradation. We aimed to integrate the profile of E3s in rat
      kidney and examine the changes in protein abundance of the selected E3s in
      response to 1-deamino-8-D-arginine vasopressin (dDAVP) stimulation/withdrawal.
      Sprague-Dawley rats were infused with vehicle (n = 13), dDAVP for 5 days (n =
      13), or dDAVP was withdrawn for periods (15 min, 30 min, 1, 3, 6, 12, or 24 h)
      after 5-day infusion (n = 46). Total RNA was isolated from the inner medulla (IM)
      for transcriptome analysis. Plasma membrane (PM)- or intracellular vesicle (ICV)
      enriched fractions of whole kidney were immunoisolated for liquid chromatography
      tandem mass spectrometry analysis. dDAVP infusion for 5 days (D5d) significantly
      increased urine osmolality, which was maintained during 3-h withdrawal of dDAVP
      after 5-day infusion (D5d-3h). Consistent with this, aquaporin-2 (AQP2)
      expression in the PM fractions of D5d and D5d-3h increased, whereas AQP2
      expression in the ICV fractions of D5d-3h was further increased, indicating
      internalization of AQP2. Transcriptome analysis revealed 86 genes of E3s and LC
      MS/MS analysis demonstrated 16 proteins of E3s. Among these, seven E3s (BRCA1,
      UBR4, BRE1B, UHRF1, NEDD4, CUL5, and FBX6) were shared. RT-PCR demonstrated mRNA
      expressions of the seven identified E3s in the kidney, and immunoblotting
      demonstrated changes in protein abundance of the selected E3s (BRE1B, NEDD4, and
      CUL5) in response to dDAVP stimulation/withdrawal or lithium-induced nephrogenic
      diabetes insipidus. The rate of AQP2 degradation was retarded in mpkCCDc14 cells
      with small interfering RNA-mediated knockdown of NEDD4 or CUL5. Taken together,
      identified E3s could be involved in the degradation of proteins associated with
      vasopressin-induced urine concentration.

PMID- 21734100
TI  - Osteopontin deficiency protects against aldosterone-induced inflammation,
      oxidative stress, and interstitial fibrosis in the kidney.
AB  - Osteopontin (OPN) has been implicated in the pathology of several renal
      conditions. Recently, we demonstrated in vitro that aldosterone has important
      roles in collagen synthesis by inducing OPN (Irita J, Okura T, Kurata M, Miyoshi
      K, Fukuoka T, Higaki J. Hypertension 51: 507-513, 2008). The aim of the present
      study was to clarify the roles of OPN in aldosterone-mediated renal fibrosis by
      infusing aldosterone into either wild-type (WT) or OPN knockout mice (OPN(-/-)).
      We used uninephrectomized mice treated with aldosterone and high salt to
      exacerbate renal fibrosis. After 4 wk of treatment with aldosterone, we showed
      similar increases in systolic blood pressure in both strains of mice. Urine
      albumin excretion was greater in aldosterone-infused WT mice than in aldosterone
      infused OPN(-/-) mice. Immunohistochemical analysis showed high levels of OPN
      expression in aldosterone-infused WT mice. Interstitial fibrosis and inflammatory
      infiltrations were increased in aldosterone-infused WT mice compared with either
      vehicle-infused WT or aldosterone-infused OPN(-/-) mice. These changes were
      ameliorated markedly by eplerenone treatment in aldosterone-infused WT mice.
      Aldosterone-infused WT mice also had increased expression of NADPH oxidase
      subunits compared with aldosterone-infused OPN(-/-) mice. We observed a marked
      increase in oxidative stress markers in aldosterone-infused WT mice compared with
      aldosterone-infused OPN(-/-) mice. These results indicate that OPN is a promoter
      of aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis
      in the kidney and suggest that inhibition of OPN may be a potential therapeutic
      target for prevention of renal injury.

PMID- 21734101
TI  - GABA(B)-mediated inhibition of multiple modes of glutamate release in the nucleus
      of the solitary tract.
AB  - In the caudal portions of the solitary tract (ST) nucleus, primary sensory
      afferents fall into two broad classes based on the expression of transient
      receptor potential vanilloid type 1 (TRPV1) receptors. Both afferent classes
      (TRPV1+/-) have indistinguishable glutamate release mechanisms for ST-evoked
      excitatory postsynaptic currents (EPSCs). However, TRPV1+ terminals release
      additional glutamate from a unique, TRPV1-operated vesicle pool that is
      temperature sensitive and facilitated by ST activity to generate asynchronous
      EPSCs. This study tested whether presynaptic gamma-aminobutyric acid (GABA)(B)
      receptors inhibit both the evoked and TRPV1-operated release mechanisms on second
      order ST nucleus neurons. In horizontal slices, shocks activated single ST axons
      and evoked the time-invariant (latency jitter <200 MUs), glutamatergic EPSCs,
      which identified second-order neurons. Gabazine eliminated GABA(A) responses in
      all recordings. The GABA(B) agonist baclofen inhibited the amplitude of ST-EPSCs
      from both TRPV1+ and TRPV1- afferents with a similar EC(50) (~1.2 MUM). In TTX,
      GABA(B) activation decreased miniature EPSC (mEPSC) rates but not amplitudes,
      suggesting presynaptic actions downstream from terminal excitability. With
      calcium entry through voltage-activated calcium channels blocked by cadmium,
      baclofen reduced mEPSC frequency, indicating that GABA(B) reduced vesicle release
      by TRPV1-dependent calcium entry. GABA(B) activation also reduced temperature
      evoked increases in mEPSC frequency, which relies on TRPV1. Our studies indicate
      that GABA(B) G protein-coupled receptors are uniformly distributed across all ST
      primary afferent terminals and act at multiple stages of the excitation-release
      cascades to suppress both action potential-triggered and TRPV1-coupled glutamate
      transmission pathways. Moreover, the segregated release cascades within TRPV1+ ST
      primary afferents represent independent, potential targets for differential
      modulation.

PMID- 21734102
TI  - Somatic calcium level reports integrated spiking activity of cerebellar
      interneurons in vitro and in vivo.
AB  - We examined the relationship between somatic Ca2+ signals and spiking activity of
      cerebellar molecular layer interneurons (MLIs) in adult mice. Using two-photon
      microscopy in conjunction with cell-attached recordings in slices, we show that
      in tonically firing MLIs loaded with high-affinity Ca2+ probes, Ca2+-dependent
      fluorescence transients are absent. Spike-triggered averages of fluorescence
      traces for MLIs spiking at low rates revealed that the fluorescence change
      associated with an action potential is small (1% of the basal fluorescence). To
      uncover the relationship between intracellular Ca2+ concentration ([Ca2+](i)) and
      firing rates, spikes were transiently silenced with puffs of the GABA(A) receptor
      agonist muscimol. [Ca2+](i) relaxed toward basal levels following a single
      exponential whose amplitude correlated to the preceding spike frequency. The
      relaxation time constant was slow (2.5 s) and independent of the probe
      concentration. Data from parvalbumin (PV)-/- animals indicate that PV controls
      the amplitude and decay time of spike-triggered averages as well as the time
      course of [Ca2+](i) relaxations following spike silencing. The [Ca2+](i) signals
      were sensitive to the L-type Ca2+ channel blocker nimodipine and insensitive to
      ryanodine. In anesthetized mice, as in slices, fluorescence traces from most MLIs
      did not show spontaneous transients. They nonetheless responded to muscimol
      iontophoresis with relaxations similar to those obtained in vitro, suggesting a
      state of tonic firing with estimated spiking rates ranging from 2 to 30 Hz.
      Altogether, the [Ca2+](i) signal appears to reflect the integral of the spiking
      activity in MLIs. We propose that the muscimol silencing strategy can be extended
      to other tonically spiking neurons with similar [Ca2+](i) homeostasis.

PMID- 21734103
TI  - Strong interactions between spinal cord networks for locomotion and scratching.
AB  - Distinct rhythmic behaviors involving a common set of motoneurons and muscles can
      be generated by separate central nervous system (CNS) networks, a single network,
      or partly overlapping networks in invertebrates. Less is known for vertebrates.
      Simultaneous activation of two networks can reveal overlap or interactions
      between them. The turtle spinal cord contains networks that generate locomotion
      and three forms of scratching (rostral, pocket, and caudal), having different
      knee-hip synergies. Here, we report that in immobilized spinal turtles,
      simultaneous delivery of types of stimulation, which individually evoked forward
      swimming and one form of scratching, could 1) increase the rhythm frequency; 2)
      evoke switches, hybrids, and intermediate motor patterns; 3) recruit a swim motor
      pattern even when the swim stimulation was reduced to subthreshold intensity; and
      4) disrupt rhythm generation entirely. The strength of swim stimulation could
      influence the result. Thus even pocket scratching and caudal scratching, which do
      not share a knee-hip synergy with forward swimming, can interact with swim
      stimulation to alter both rhythm and pattern generation. Model simulations were
      used to explore the compatibility of our experimental results with hypothetical
      network architectures for rhythm generation. Models could reproduce experimental
      observations only if they included interactions between neurons involved in swim
      and scratch rhythm generation, with maximal consistency between simulations and
      experiments attained using a model architecture in which certain neurons
      participated actively in both swim and scratch rhythmogenesis. Collectively,
      these findings suggest that the spinal cord networks that generate locomotion and
      scratching have important shared components or strong interactions between them.

PMID- 21734104
TI  - Hydrogen sulfide augments synaptic neurotransmission in the nucleus of the
      solitary tract.
AB  - Within the brain stem, the nucleus tractus solitarii (NTS) serves as a principal
      central site for sensory afferent integration from the cardiovascular and
      respiratory reflexes. Neuronal activity and synaptic transmission in the NTS are
      highly pliable and subject to neuromodulation. In the central nervous system,
      hydrogen sulfide (H2S) is a gasotransmitter generated primarily by the enzyme
      cystathionine-beta-synthase (CBS). We sought to determine the role of H2S, and
      its generation by CBS, in NTS excitability. Real-time RT-PCR, immunoblot, and
      immunohistochemistry analysis identified the presence of CBS in the NTS. Patch
      clamp electrophysiology in brain stem slices examined excitatory postsynaptic
      currents (EPSCs) and membrane properties in monosynaptically driven NTS neurons.
      Confocal imaging of labeled afferent synaptic terminals in NTS slices monitored
      intracellular calcium. Exogenous H2S significantly increased the amplitude of
      evoked solitary tract (TS)-EPSCs, frequency of miniature (m)EPSCs, and
      presynaptic terminal calcium fluorescence in the NTS. H2S did not alter action
      potential discharge or postsynaptic properties. On the other hand, the CBS
      inhibitor aminooxyacetate (AOA) significantly reduced the amplitude of TS-EPSCs
      and presynaptic terminal calcium fluorescence in the NTS without altering
      postsynaptic properties. Taken together, these data support a presynaptic role
      for endogenous H2S in modulation of excitatory neurotransmission in the NTS.

PMID- 21734105
TI  - Locomotor-related activity of GABAergic interneurons localized in the
      ventrolateral region in the isolated spinal cord of neonatal mice.
AB  - Inhibitory neurons are an essential element of the locomotor network in the
      mammalian spinal cord. However, little is known about the firing pattern and
      synaptic modulation during locomotion in the majority of them. In this study, we
      performed whole cell recording in visually identified ventrolaterally located
      GABAergic neurons (VL-GNs) in the rostral (L2 segment) and caudal (L5 segment)
      lumbar cord using isolated spinal cord preparations taken from glutamate
      decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mouse neonates.
      These neurons did not respond to electrical stimulation of the ventral root,
      indicating that they were not Renshaw cells. Ninety-five percent of VL-GNs in the
      L2 segment and fifty percent of those in the L5 segment showed significant
      rhythmic firing during locomotor-like rhythmic activity induced by bath
      application of 5-HT and NMDA. Seventy percent of these neurons fired mainly
      during the extensor phase, and twenty-five percent fired mainly during the flexor
      phase. Voltage-clamp recordings revealed that most of these neurons received
      rhythmic inhibition during the nonfiring phase and excitatory synaptic inputs
      during the firing phase. Morphological examination of recorded neurons filled
      with neurobiotin showed that their soma was located lateral to the motoneuron
      pool and that they extended their processes into the local ipsilateral
      ventromedial region and dorsal regions. The present study indicates that these
      GABAergic interneurons located in the ventrolateral region adjacent to the
      motoneuron pool are rhythmically active during locomotion and involved in the
      inhibitory modulation of local locomotor network in the lumbar spinal cord.

PMID- 21734106
TI  - Expression patterns of nicotinic subunits alpha2, alpha7, alpha8, and beta1
      affect the kinetics and pharmacology of ACh-induced currents in adult bee
      olfactory neuropiles.
AB  - Acetylcholine (ACh) is the main excitatory neurotransmitter of the insect brain,
      where nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic
      synaptic transmission. In the honeybee Apis mellifera, nAChRs are expressed in
      diverse structures including the primary olfactory centers of the brain, the
      antennal lobes (ALs) and the mushroom bodies (MBs), where they participate in
      olfactory information processing. To understand the nature and properties of the
      nAChRs involved in these processes, we performed a pharmacological and molecular
      characterization of nAChRs on cultured Kenyon cells of the MBs, using whole cell
      patch-clamp recordings combined with single-cell RT-PCR. In all cells,
      applications of ACh as well as nicotinic agonists such as nicotine and
      imidacloprid induced inward currents with fast desensitization. These currents
      were fully blocked by saturating doses of the antagonists alpha-bungarotoxin
      (alpha-BGT), dihydroxy-beta-erythroidine (DHE), and methyllycaconitine (MLA) (MLA
      >= alpha-BGT >= DHE). Molecular analysis of ACh-responding cells revealed that of
      the 11 nicotinic receptor subunits encoded within the honeybee genome, alpha2,
      alpha8, and beta1 subunits were expressed in adult Kenyon cells. Comparison with
      the expression pattern of adult AL cells revealed the supplementary presence of
      subunit alpha7, which could be responsible for the kinetic and pharmacological
      differences observed when comparing ACh-induced currents from AL and Kenyon
      cells. Together, our data demonstrate the existence of functional nAChRs on adult
      MB Kenyon cells that differ from nAChRs on AL cells in both their molecular
      composition and pharmacological properties, suggesting that changing receptor
      subsets could mediate different processing functions depending on the brain
      structure within the olfactory pathway.

PMID- 21734107
TI  - Manifold reaching paradigm: how do we handle target redundancy?
AB  - How the central nervous system coordinates the many intrinsic degrees of freedom
      of the musculoskeletal system is a recurrent question in motor control. Numerous
      studies addressed it by considering redundant reaching tasks such as point-to
      point arm movements, for which many joint trajectories and muscle activations are
      usually compatible with a single goal. There exists, however, a different,
      extrinsic kind of redundancy that is target redundancy. Many times, indeed, the
      final point to reach is neither specified nor unique. In this study, we aim to
      understand how the central nervous system tackles such an extrinsic redundancy by
      considering a reaching-to-a-manifold paradigm, more specifically an arm pointing
      to a long vertical bar. In this case, the endpoint is not defined a priori and,
      therefore, subjects are free to choose any point on the bar to successfully
      achieve the task. We investigated the strategies used by subjects to handle this
      presented choice. Our results indicate both intersubject and intertrial
      consistency with respect to the freedom provided by the task. However, the
      subjects' behavior is found to be more variable than during classical point-to
      point reaches. Interestingly, the average arm trajectories to the bar and the
      structure of intertrial endpoint variations could be explained via stochastic
      optimal control with an energy/smoothness expected cost and signal-dependent
      motor noise. We conclude that target redundancy is first overcome during movement
      planning and then exploited during movement execution, in agreement with
      stochastic optimal feedback control principles, which illustrates how the
      complementary problems of goal and movement selection may be resolved at once.

PMID- 21734108
TI  - Face categorization in visual scenes may start in a higher order area of the
      right fusiform gyrus: evidence from dynamic visual stimulation in neuroimaging.
AB  - How a visual stimulus is initially categorized as a face by the cortical face
      processing network remains largely unclear. In this study we used functional MRI
      to study the dynamics of face detection in visual scenes by using a paradigm in
      which scenes containing faces or cars are revealed progressively as they emerge
      from visual noise. Participants were asked to respond as soon as they detected a
      face or car during the noise sequence. Among the face-sensitive regions
      identified based on a standard localizer, a high-level face-sensitive area, the
      right fusiform face area (FFA), showed the earliest difference between face and
      car activation. Critically, differential activation in FFA was observed before
      differential activation in the more posteriorly located occipital face area
      (OFA). A whole brain analysis confirmed these findings, with a face-sensitive
      cluster in the right fusiform gyrus being the only cluster showing face
      preference before successful behavioral detection. Overall, these findings
      indicate that following generic low-level visual analysis, a face stimulus
      presented in a gradually revealed visual scene is first detected in the right
      middle fusiform gyrus, only after which further processing spreads to a network
      of cortical and subcortical face-sensitive areas (including the posteriorly
      located OFA). These results provide further evidence for a nonhierarchical
      organization of the cortical face-processing network.

PMID- 21734109
TI  - Motor demand-dependent improvement in accuracy following low-frequency
      transcranial magnetic stimulation of left motor cortex.
AB  - The role of primary motor cortex (M1) in the control of voluntary movements is
      still unclear. In brain functional imaging studies of unilateral hand
      performance, bilateral M1 activation is inconsistently observed, and disruptions
      of M1 using repetitive transcranial magnetic stimulation (rTMS) lead to variable
      results in the hand motor performance. As the motor tasks differed qualitatively
      in these studies, it is conceivable that M1 contribution differs depending on the
      level of skillfulness. The objective of the present study was to determine
      whether M1 contribution to hand motor performance differed depending on the level
      of precision of the motor task. Here, we used low-frequency rTMS of left M1 to
      determine its effect on the performance of a pointing task that allows the
      parametric increase of the level of precision and thereby increase the level of
      required precision quantitatively. We found that low-frequency rTMS improved
      performance in both hands for the task with the highest demand on precision,
      whereas performance remained unchanged for the tasks with lower demands. These
      results suggest that the functional relevance of M1 activity for motor
      performance changes as a function of motor demand. The bilateral effect of rTMS
      to left M1 would also support the notion of M1 functions at a higher level in
      motor control by integrating afferent input from nonprimary motor areas.

PMID- 21734110
TI  - Mechanisms and time course of vocal learning and consolidation in the adult
      songbird.
AB  - In songbirds, the basal ganglia outflow nucleus LMAN is a cortical analog that is
      required for several forms of song plasticity and learning. Moreover, in adults,
      inactivating LMAN can reverse the initial expression of learning driven via
      aversive reinforcement. In the present study, we investigated how LMAN
      contributes to both reinforcement-driven learning and a self-driven recovery
      process in adult Bengalese finches. We first drove changes in the fundamental
      frequency of targeted song syllables and compared the effects of inactivating
      LMAN with the effects of interfering with N-methyl-d-aspartate (NMDA) receptor
      dependent transmission from LMAN to one of its principal targets, the song
      premotor nucleus RA. Inactivating LMAN and blocking NMDA receptors in RA caused
      indistinguishable reversions in the expression of learning, indicating that LMAN
      contributes to learning through NMDA receptor-mediated glutamatergic transmission
      to RA. We next assessed how LMAN's role evolves over time by maintaining learned
      changes to song while periodically inactivating LMAN. The expression of learning
      consolidated to become LMAN independent over multiple days, indicating that this
      form of consolidation is not completed over one night, as previously suggested,
      and instead may occur gradually during singing. Subsequent cessation of
      reinforcement was followed by a gradual self-driven recovery of original song
      structure, indicating that consolidation does not correspond with the lasting
      retention of changes to song. Finally, for self-driven recovery, as for
      reinforcement-driven learning, LMAN was required for the expression of initial,
      but not later, changes to song. Our results indicate that NMDA receptor-dependent
      transmission from LMAN to RA plays an essential role in the initial expression of
      two distinct forms of vocal learning and that this role gradually wanes over a
      multiday process of consolidation. The results support an emerging view that
      cortical-basal ganglia circuits can direct the initial expression of learning via
      top-down influences on primary motor circuitry.

PMID- 21734111
TI  - Altered activation patterns by triceps surae stretch reflex pathways in acute and
      chronic spinal cord injury.
AB  - Spinal reflexes are modified by spinal cord injury (SCI) due the loss of
      excitatory inputs from supraspinal structures and changes within the spinal cord.
      The stretch reflex is one of the simplest pathways of the central nervous system
      and was used presently to evaluate how inputs from primary and secondary muscle
      spindles interact with spinal circuits before and after spinal transection (i.e.,
      spinalization) in 12 adult decerebrate cats. Seven cats were spinalized and
      allowed to recover for 1 mo (i.e., chronic spinal state), whereas 5 cats were
      evaluated before (i.e., intact state) and after acute spinalization (i.e., acute
      spinal state). Stretch reflexes were evoked by stretching the left triceps surae
      (TS) muscles. The force evoked by TS muscles was recorded along with the activity
      of several hindlimb muscles. Stretch reflexes were abolished in the acute spinal
      state due to an inability to activate TS muscles, such as soleus (Sol) and
      lateral gastrocnemius (LG). In chronic spinal cats, reflex force had partly
      recovered but Sol and LG activity remained considerably depressed, despite the
      fact that injecting clonidine could recruit these muscles during locomotor-like
      activity. In contrast, other muscles not recruited in the intact state, most
      notably semitendinosus and sartorius, were strongly activated by stretching TS
      muscles in chronic spinal cats. Therefore, stretch reflex pathways from TS
      muscles to multiple hindlimb muscles undergo functional reorganization following
      spinalization, both acute and chronic. Altered activation patterns by stretch
      reflex pathways could explain some sensorimotor deficits observed during
      locomotion and postural corrections after SCI.

PMID- 21734112
TI  - Enhanced information output from shotgun proteomics data by protein
      quantification and peptide quality control (PQPQ).
AB  - We present a tool to improve quantitative accuracy and precision in mass
      spectrometry based on shotgun proteomics: protein quantification by peptide
      quality control, PQPQ. The method is based on the assumption that the
      quantitative pattern of peptides derived from one protein will correlate over
      several samples. Dissonant patterns arise either from outlier peptides or because
      of the presence of different protein species. By correlation analysis, protein
      quantification by peptide quality control identifies and excludes outliers and
      detects the existence of different protein species. Alternative protein species
      are then quantified separately. By validating the algorithm on seven data sets
      related to different cancer studies we show that data processing by protein
      quantification by peptide quality control improves the information output from
      shotgun proteomics. Data from two labeling procedures and three different
      instrumental platforms was included in the evaluation. With this unique method
      using both peptide sequence data and quantitative data we can improve the
      quantitative accuracy and precision on the protein level and detect different
      protein species.

PMID- 21734113
TI  - Abscisic acid plays an important role in the regulation of strawberry fruit
      ripening.
AB  - The plant hormone abscisic acid (ABA) has been suggested to play a role in fruit
      development, but supporting genetic evidence has been lacking. Here, we report
      that ABA promotes strawberry (Fragaria ananassa) fruit ripening. Using a newly
      established Tobacco rattle virus-induced gene silencing technique in strawberry
      fruit, the expression of a 9-cis-epoxycarotenoid dioxygenase gene (FaNCED1),
      which is key to ABA biosynthesis, was down-regulated, resulting in a significant
      decrease in ABA levels and uncolored fruits. Interestingly, a similar uncolored
      phenotype was observed in the transgenic RNA interference (RNAi) fruits, in which
      the expression of a putative ABA receptor gene encoding the magnesium chelatase H
      subunit (FaCHLH/ABAR) was down-regulated by virus-induced gene silencing. More
      importantly, the uncolored phenotype of the FaNCED1-down-regulated RNAi fruits
      could be rescued by exogenous ABA, but the ABA treatment could not reverse the
      uncolored phenotype of the FaCHLH/ABAR-down-regulated RNAi fruits. We observed
      that down-regulation of the FaCHLH/ABAR gene in the RNAi fruit altered both ABA
      levels and sugar content as well as a set of ABA- and/or sugar-responsive genes.
      Additionally, we showed that exogenous sugars, particularly sucrose, can
      significantly promote ripening while stimulating ABA accumulation. These data
      provide evidence that ABA is a signal molecule that promotes strawberry ripening
      and that the putative ABA receptor, FaCHLH/ABAR, is a positive regulator of
      ripening in response to ABA.

PMID- 21734114
TI  - Functional analysis of two isoforms of leaf-type ferredoxin-NADP(+)
      oxidoreductase in rice using the heterologous expression system of Arabidopsis.
AB  - Ferredoxin-NADP(+)-oxidoreductase (FNR) mediates electron transfer between
      ferredoxin (Fd) and NADP(+); therefore, it is a key enzyme that provides the
      reducing power used in the Calvin cycle. Other than FNR, nitrite reductase,
      sulfite reductase, glutamate synthase, and Fd-thioredoxin reductase also accept
      electrons from Fd, an electron carrier protein in the stroma. Therefore, the
      regulation of electron partitioning in the chloroplast is important for
      photosynthesis and other metabolic pathways. The regulatory mechanism of electron
      partitioning, however, remains to be elucidated. We found, by taking advantage of
      a gain-of-function approach, that expression of two rice (Oryza sativa) full
      length cDNAs of leaf-type FNRs (OsLFNR1 and OsLFNR2) led to altered chlorophyll
      fluorescence and growth in Arabidopsis (Arabidopsis thaliana) and rice. We
      revealed that overexpression of the OsLFNR1 and OsLFNR2 full-length cDNAs
      resulted in distinct phenotypes despite the high sequence similarity between
      them. Expression of OsLFNR1 affected the nitrogen assimilation pathway without
      inhibition of photosynthesis under normal conditions. On the other hand, OsLFNR2
      expression led to the impairment of photosynthetic linear electron transport as
      well as Fd-dependent cyclic electron flow around photosystem I. The endogenous
      protein level of OsLFNR was found to be suppressed in both OsLFNR1- and OsLFNR2
      overexpressing rice plants, leading to changes in the stoichiometry of the two
      LFNR isoforms within the thylakoid and soluble fractions. Thus, we propose that
      the stoichiometry of two LFNR isoforms plays an important role in electron
      partitioning between carbon fixation and nitrogen assimilation.

PMID- 21734115
TI  - Multiple intraventricular neurocysticercal cysts treated with endoscopy without
      antiparasitic therapy.

PMID- 21734116
TI  - Ivermectin mass drug administration to humans disrupts malaria parasite
      transmission in Senegalese villages.
AB  - Ivermectin mass drug administration (MDA) to humans is used to control
      onchocerciasis and lymphatic filariasis. Recent field studies have shown an added
      killing effect of ivermectin MDA against malaria vectors. We report that
      ivermectin MDA reduced the proportion of Plasmodium falciparum infectious
      Anopheles gambiae sensu stricto (s.s.) in treated villages in southeastern
      Senegal. Ivermectin MDA is a different delivery method and has a different mode
      of action from current malaria control agents. It could be a powerful and
      synergistic new tool to reduce malaria transmission in regions with epidemic or
      seasonal malaria transmission, and the prevalence and intensity of neglected
      tropical diseases.

PMID- 21734117
TI  - Usefulness of polymerase chain reaction to supplement field microscopy in a pre
      selected population with a high probability of malaria infections.
AB  - This study determines the use of nested PCR as a diagnostic tool to supplement
      field microscopy in symptomatic individuals suspected of being positive for
      malaria, and it explores its role in active case detection to identify
      asymptomatic parasite carriers. In symptomatic individuals, compared with PCR,
      microscopy had a sensitivity of 86.6% (95% confidence interval [CI] = 77.8-92.4)
      and specificity of 100% (95% CI = 96.9-100). During active case detection, two
      asymptomatic persons were diagnosed as having vivax malaria by polymerase chain
      reaction (PCR) but not microscopy. Currently, PCR is being carried out in Sri
      Lanka only for population surveys to estimate the hidden reservoir of malaria.
      Based on the results of this study and because of cost considerations, pooled PCR
      will be used in the future to screen samples from clinically suspected foci to
      increase the proportion of malaria cases detected. This strategy will assist the
      success of the malaria elimination program in Sri Lanka.

PMID- 21734118
TI  - Intermittent preventive treatment with sulfadoxine-pyrimethamine against malaria
      and anemia in pregnant women.
AB  - The effectiveness of intermittent preventive treatment during pregnancy with
      sulfadoxine-pyrimethamine (IPTp-SP) against malaria and anemia is unclear because
      of the spread of SP-resistant Plasmodium falciparum. This study evaluates the
      effectiveness of IPTp-SP among pregnant women attending the antenatal clinic at
      Korle-Bu Teaching Hospital in Accra, Ghana. A cross-sectional study comparing
      malaria and anemia prevalence among pregnant women using IPTp-SP with non-IPTp-SP
      users was conducted during June-August 2009. A total of 363 pregnant women (202
      of IPTp users and 161 non-IPTp users) were recruited. A total of 15.3% of IPTp
      users had malaria compared with 44.7% of non-IPTp users (P < 0.001). A total of
      58.4% of non-IPTp users were anemic compared with 22.8% of IPTp users (P <
      0.001). When we controlled for other variables, the difference in the prevalence
      of malaria (odds ratio = 0.18, 95% confidence interval = 0.08-0.37) and anemia
      (odds ratio = 0.20, 95% confidence interval = 0.12-0.34) remained significant.
      The recommended IPTp-SP regimen is useful in preventing malaria and anemia among
      pregnant women in Ghana.

PMID- 21734119
TI  - Molecular epidemiology of malaria in Cameroon. XXX. sequence analysis of
      Plasmodium falciparum ATPase 6, dihydrofolate reductase, and dihydropteroate
      synthase resistance markers in clinical isolates from children treated with an
      artesunate-sulfadoxine-pyrimethamine combination.
AB  - Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase
      (dhps) genes are reliable molecular markers for antifolate resistance. The P.
      falciparum ATPase 6 (pfatp6) gene has been proposed to be a potential marker for
      artemisinin resistance. In our previous clinical study, we showed that artesunate
      sulfadoxine-pyrimethamine is highly effective against uncomplicated malaria in
      Yaounde, Cameroon. In the present study, dhfr, dhps, and pfatp6 mutations in P.
      falciparum isolates obtained from children treated with artesunate-sulfadoxine
      pyrimethamine were determined. All 61 isolates had wild-type Pfatp6 263, 623, and
      769 alleles, and 11 (18%) had a single E431K substitution. Three additional
      mutations, E643Q, E432K, and E641Q, were detected. The results did not indicate
      any warning signal of serious concern (i.e., no parasites were seen with
      quintuple dhfr-dhps, DHFR Ile164Leu, or pfatp6 mutations), as confirmed by the
      high clinical efficacy of artesunate-sulfadoxine-pyrimethamine. Further studies
      are required to identify a molecular marker that reliably predicts artemisinin
      resistance.

PMID- 21734120
TI  - Use of an innovative, affordable, and open-source short message service-based
      tool to monitor malaria in remote areas of Uganda.
AB  - Quality health management requires timely and accurate data, and paper-based
      reporting does not fill this role adequately. The introduction of malaria rapid
      diagnostic tests and the availability of wireless communications present an
      opportunity to open direct data transmission and feedback between peripheral
      health workers and central managers. In November 2009, the Uganda Ministry of
      Health deployed a short message service-based reporting system in two districts.
      At a set-up cost of $100/health facility, local technician support of $ 400 per
      month, and a cost of $0.53/week/clinic, the SMS reporting system was started at
      more than 140 clinics. Positivity rates for rapid diagnostic tests and
      artemisinin combination therapy stock outs were 48% and 54% in Kabale and 71% and
      54% in Gulu, among other reports, at more than 85% health facilities reporting
      weekly and without monetary incentives or additional supervision. The SMS-based
      reporting systems have potential to improve timeliness in reporting of specific,
      time-sensitive metrics at modest cost, while by-passing current bottlenecks in
      the flow of data. With the development of specific capacity to manage stock data
      at district level, the availability of timely data offers potential to address
      commodity distribution problems and reduce stock-outs.

PMID- 21734121
TI  - Antimalarial drug sensitivity profile of western Kenya Plasmodium falciparum
      field isolates determined by a SYBR Green I in vitro assay and molecular
      analysis.
AB  - In vitro drug sensitivity and molecular analyses of Plasmodium falciparum track
      drug resistance. DNA-binding fluorescent dyes like SYBR Green I may allow field
      laboratories, proximal to P. falciparum collection sites, to conduct drug assays.
      In 2007-2008, we assayed 121 P. falciparum field isolates from western Kenya for
      50% inhibitory concentrations (IC(50)) against 6 antimalarial drugs using a SYBR
      Green I in vitro assay: 91 immediate ex vivo (IEV) and 30 culture-adapted, along
      with P. falciparum reference clones D6 (chloroquine [CQ] sensitive) and W2 (CQ
      resistant). We also assessed P. falciparum mdr1 (Pfmdr1) copy number and single
      nucleotide polymorphisms (SNPs) at four codons. The IC(50)s for IEV and culture
      adapted P. falciparum isolates were similar, and approximated historical IC(50)s.
      For Pfmdr1, mean copy number was 1, with SNPs common at codons 86 and 184. The
      SYBR Green I assay adapted well to our field-based laboratory, for both IEV and
      culture-adapted P. falciparum, warranting continued use.

PMID- 21734122
TI  - Malaria caused by Plasmodium vivax complicated by acalculous cholecystitis.
AB  - We report the first adult cases of acute acalculous cholecystitis (AAC)
      exclusively caused by infections with Plasmodium vivax. We reviewed the previous
      cases of AAC occurring during malaria, compared and contrasted the variables of
      previously reported cases with the cases reported here, examined the pathogenic
      link between malaria and AAC, and considered the diagnostic pitfalls and
      treatment implications as they applied to clinical outcomes in patients with this
      serious and potentially underrecognized illness.

PMID- 21734123
TI  - Reference intervals for common laboratory tests in Melanesian children.
AB  - Pediatric reference intervals for biochemical tests are often derived from
      studies in Western countries and may not be applicable to the developing world.
      No such intervals exist for Melanesian populations. The aim of this study was to
      provide specific reference intervals for children from Papua New Guinea (PNG). We
      assayed plasma from 327 healthy Melanesian children living in Madang Province for
      common biochemical and hematological analytes. We used well-validated
      commercially available assay methodology. Compared with reference intervals from
      children from Western countries and/or African children, there were substantial
      differences in hemoglobin, soluble transferrin receptor, ferritin, calcium,
      phosphate, and C-reactive protein. Differences in the upper limits of reference
      intervals for bilirubin and alanine aminotransferase were also observed.
      Available reference intervals from Western and African countries may be
      inappropriate in PNG and other Melanesian countries. This has implications for
      clinical care and safety monitoring in pharmaceutical intervention trials and
      vaccine studies.

PMID- 21734124
TI  - Atypical lesions as a sign of cutaneous dissemination of visceral leishmaniasis
      in a human immunodeficiency virus-positive patient simultaneously infected by two
      viscerotropic Leishmania species.
AB  - Leishmaniasis is considered an emerging opportunistic disease in human
      immunodeficiency virus (HIV)-infected patients who have considerably variable
      clinical presentation. We report a patient with visceral leishmaniasis who had
      unexpected clinical aspects (atypical cutaneous lesions appearing after long-term
      evidence of visceral parasites). The patient had hepatoesplenomegaly in the
      absence of fever, but was otherwise generally healthy. The HIV viral load was low
      despite severe immunossupression (low lymphocyte proliferation and low level of
      interferon-gamma, concomitant with a high lymphocyte activation status).
      Surprisingly, two Leishmania strains were isolated from his bone marrow (typical
      L. infantum sequence MON-1, type A) and skin (L. donovani MON-2 sequence); this
      second strain had not been previously identified in Brazil. The association of
      visceral leishmaniasis and HIV/acquired immunodeficiency syndrome is a largely
      unknown disease, particularly in areas in which leishmaniasis is not endemic.
      Such atypical cases indicate that this disease can be undiagnosed in clinical
      settings.

PMID- 21734125
TI  - Variation in clinical presentation and genotype of causative Leishmania major
      strain in cutaneous leishmaniasis in north and south Afghanistan.
AB  - A different clinical picture and therapeutic response were observed when data
      from Leishmania major-infected Dutch military personnel stationed in southern (N
      = 8) and northern (N = 169) Afghanistan were analyzed. Clinical presentation of
      cutaneous leishmaniasis in personnel in the south was milder and seemed to
      respond better to antileishmanial treatment; molecular analyses of parasite
      isolates seem to indicate that these differences may be genetic.

PMID- 21734126
TI  - A patient presenting with diffuse cutaneous leishmaniasis (DCL) as a first
      indicator of HIV infection in India.
AB  - Opportunistic parasitic infections such as leishmaniasis are common in human
      immunodeficiency virus (HIV)-infected patients and are usually acquired several
      days after initial diagnosis of HIV infection. Here, we report on a patient who
      presented with diffuse cutaneous leishmaniasis (DCL) caused by Leishmania tropica
      as the first and only clinical manifestation of HIV infection. To the best of our
      knowledge, this is the first case that illustrates that DCL could be the first
      clinical indicator of HIV infection. Cutaneous leishmaniasis (CL) and DCL are
      becoming frequent opportunistic infections in HIV-infected individuals throughout
      the world. To date, all documented cases of CL and HIV coinfections have been
      reported in patients who were known cases of HIV and who subsequently developed
      CL. In this report, we present a case that illustrates that DCL could be the
      first clinical indicator of HIV infection.

PMID- 21734127
TI  - Phase IV trial of miltefosine in adults and children for treatment of visceral
      leishmaniasis (kala-azar) in Bangladesh.
AB  - Miltefosine (target dose of 2.5 mg/kg/day for 28 days) is the recommended
      treatment for visceral leishmaniasis (kala-azar) in Bangladesh on the basis of
      data from India. We evaluated miltefosine in a phase IV trial of 977 patients in
      Bangladesh. At the six-month final follow up, 701 were cured. 24 showed initial
      treatment failure, and 95 showed treatment failure at 6 months, although 73 of
      the 95 showed treatment failure solely by the criterion of low hemoglobin values.
      One hundred twenty-one patients were not assessable. With the conservative
      assumption that all low hemoglobin values represented treatment failure, the
      final per protocol cure rate was 85%. Of 13 severe adverse events, 6 led to
      treatment discontinuation and 7 resulted in deaths, but only 1 death (associated
      with diarrhea) could be attributed to drug. Nearly all non-serious adverse events
      were gastrointestinal: vomiting in 25% of patients and diarrhea in 8% of
      patients. Oral miltefosine is an attractive alternative to intramuscular antimony
      and intravenous amphotericin B for treatment of kala-azar in Bangladesh.

PMID- 21734128
TI  - Lesion size correlates with Leishmania antigen-stimulated TNF-levels in human
      cutaneous leishmaniasis.
AB  - Cutaneous leishmaniasis (CL) is a worldwide disease endemic in several regions of
      the globe. The hallmark of CL is skin ulcers likely driven by efforts of the
      immune system to control Leishmania growth. Cytokines, such as tumor necrosis
      factor (TNF) and interferon-gamma can control disease progression in animal
      models. Nevertheless, the impact of these cytokines in CL ulcer outcome is not
      well established in humans. In this study, 96 CL patients from an endemic area of
      Leishmania braziliensis were enrolled for a follow-up study that consisted of
      clinical and immunological evaluations in a 2-year period. Statistical analysis
      revealed that healing time (P = 0.029), age (P = 0.002), and TNF levels (P =
      0.0002) positively correlate with ulcer size at the time of the first clinical
      evaluation. Our findings suggest that ulcer size correlates with healing time and
      TNF levels support the use of TNF inhibitors combined with standard therapy to
      improve healing in CL patients with severe lesions.

PMID- 21734129
TI  - Human schistosomiasis resistance to praziquantel in China: should we be worried?
AB  - The efficacy of praziquantel for the treatment of Schistosoma japonicum in humans
      is reported from a cross-sectional survey conducted in 33 villages in Sichuan
      Province. Infection prevalence was found to be 5.7% (185 infected of 3,269
      tested) in a region where 44-73% prevalence was found 9 years before. Collected
      miracidia were subjected to an in vitro test of praziquantel susceptibility. An
      effective concentration of praziquantel associated with 50% of miracidia changing
      shape was found between 10(-8) and 10(-7) M and 10(-7) and 10(-6) M for 10 and 5
      minutes of exposure, respectively. After treating infected persons two times with
      40-mg/kg doses of praziquantel, only one remained infected. Findings are reported
      from a 60-household questionnaire on attitudes and behaviors that may be
      associated with development of drug resistance. The low number of treatment
      failures and good compliance with treatment despite side effects and repeated
      annual treatments suggest that, in the near term, praziquantel remains effective
      in treating human S. japonicum infection in China.

PMID- 21734130
TI  - An integrated strategy for transmission control of Schistosoma japonicum in a
      marshland area of China: findings from a five-year longitudinal survey and
      mathematical modeling.
AB  - In 2004 an aggressive plan was instituted aiming to achieve nationwide
      transmission control of schistosomiasis by 2015. Here, we report a longitudinal
      study on the control of schistosomiasis in Anhui province, China. Using a
      mathematical model, we compared the effects of different control strategies
      implemented in the study area. During the 5-year study period, a 60.8% reduction
      in human prevalence was observed from 2005 (7.95%) to 2009 (3.1%), and snail
      infection decreased from 0.063% in 2005 to zero in 2009. Results of the model
      agree well with the first 3-year field observations and suggest continuous
      decrease in human infections in the last 2 years, whereas the last 2-year field
      observations indicated that human infections appeared to be stable even with
      continuous control. Our findings showed that the integrated control strategy was
      effective, and we speculated that other factors besides bovines might contribute
      to the local transmission of the disease.

PMID- 21734131
TI  - Heightened measures of immune complex and complement function and immune complex
      mediated granulocyte activation in human lymphatic filariasis.
AB  - The presence of circulating immune complexes (CICs) is a characteristic feature
      of human lymphatic filariasis. However, the role of CICs in modulating
      granulocyte function and complement functional activity in filarial infection is
      unknown. The levels of CICs in association with complement activation in
      clinically asymptomatic, filarial-infected patients (INF); filarial-infected
      patients with overt lymphatic pathologic changes (CPDT); and uninfected controls
      (EN) were examined. Significantly increased levels of CICs and enhanced
      functional efficiency of the classical and mannose-binding lectin pathways of the
      complement system was observed in INF compared with CPDT and EN. Polyethylene
      glycol-precipitated CICs from INF and CPDT induced significantly increased
      granulocyte activation compared with those from EN, determined by the increased
      production of neutrophil granular proteins and a variety of pro-inflammatory
      cytokines. Thus, CIC-mediated enhanced granulocyte activation and modulation of
      complement function are important features of filarial infection and disease.

PMID- 21734132
TI  - Antibody responses to the immunodominant Cryptosporidium gp15 antigen and gp15
      polymorphisms in a case-control study of cryptosporidiosis in children in
      Bangladesh.
AB  - Although Cryptospridium hominis is the dominant Cryptosporidium species infecting
      humans, immune responses to cognate antigens in C. hominis-infected persons have
      not been reported. We investigated antibody responses to the immunodominant gp15
      antigen from C. hominis and C. parvum, in C. hominis-infected Bangladeshi
      children less than five years of age with diarrhea (cases) and uninfected
      children with diarrhea (controls). We also investigated polymorphisms in the C.
      hominis gp15 sequence from cases. Serum IgG responses to gp15 from both species
      were significantly greater in cases than controls. In spite of polymorphisms in
      the gp15 sequence, there was a significant correlation between antibody levels to
      gp15 from both species, indicating cross-reactivity to conserved epitopes. Cases
      with acute diarrhea had a significantly greater serum IgA response to gp15
      compared with those with persistent diarrhea, suggesting that this response may
      be associated with protection from prolonged disease. These findings support
      further investigation of gp15 as a vaccine candidate.

PMID- 21734133
TI  - Etiology of suspected pneumonia in adults admitted to a high-dependency unit in
      Blantyre, Malawi.
AB  - The microbiologic etiology of severe pneumonia in hospitalized patients is rarely
      known in sub-Saharan Africa. Through a comprehensive diagnostic work-up, we aimed
      to identify the causative agent in severely ill patients with a clinical picture
      of pneumonia admitted to a high-dependency unit. A final diagnosis was made and
      categorized as confirmed or probable by using predefined criteria. Fifty-one
      patients were recruited (45% females), with a mean age of 35 years (range = 17-88
      years), of whom 11(22%) died. Forty-eight (94%) of the patients were seropositive
      for human immunodeficiency virus; 14 (29%) of these patients were receiving
      antiretroviral treatment. Final diagnoses were bacterial pneumonia (29%),
      Pneumocystis jirovecii pneumonia (27%), pulmonary tuberculosis (22%), and
      pulmonary Kaposi's sarcoma (16%); 39 (77%) of these cases were confirmed cases.
      Fifteen (29%) patients had multiple isolates. At least 3 of 11 viral-positive
      polymerase chain reaction (PCR) results of bronchoalveolar lavage fluid were
      attributed clinical relevance. No atypical bacterial organisms were found.

PMID- 21734134
TI  - Challenges in recognition and diagnosis of yaws in children in Papua New Guinea.
AB  - A global resurgence of yaws in developing countries highlights the need for
      reliable diagnostic criteria for this neglected infection. We conducted a
      clinical and serologic survey of 233 children less than 15 years of age who had
      clinically suspected yaws. A total of 138 (59%) cases were confirmed
      serologically, and 10 of 12 primary stage cases showed positive results for
      Treponema pallidum by a polymerase chain reaction assay that has not yet been
      validated for identification of yaws. A high proportion of cases (46%) were in
      the secondary stage; 92% of them had osteoarticular involvement, and only 24% had
      a Venereal Disease Research Laboratory titer greater than 1:32.

PMID- 21734135
TI  - Incidence of bacteremic melioidosis in eastern and northeastern Thailand.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in
      northeastern Thailand. Population-based disease burden estimates are lacking and
      limited data on melioidosis exist from other regions of the country. Using
      active, population-based surveillance, we measured the incidence of bacteremic
      melioidosis in the provinces of Sa Kaeo (eastern Thailand) and Nakhon Phanom
      (northeastern Thailand) during 2006-2008. The average annual incidence in Sa Kaeo
      and Nakhon Phanom per 100,000 persons was 4.9 (95% confidence interval [CI] = 3.9
      6.1) and 14.9 (95% CI = 13.3-16.6). The respective population mortality rates
      were 1.9 (95% CI = 1.3-2.8) and 4.4 (95% CI = 3.6-5.3) per 100,000. The case
      fatality proportion was 36% among those with known outcome. Our findings document
      a high incidence and case fatality proportion of bacteremic melioidosis in
      Thailand, including a region not traditionally considered highly endemic, and
      have potential implications for clinical management and health policy.

PMID- 21734136
TI  - Molecular characterization of clinical Burkholderia pseudomallei isolates from
      India.
AB  - Multilocus sequence typing of seven isolates of Burkholderia pseudomallei from
      India showed considerable diversity, with six different sequence types. Possible
      dissemination of melioidosis by historical trading routes is supported by links
      to strains from Southeast Asia, China, and Africa and the presence of the
      Burkholderia mallei allele of the bimA gene.

PMID- 21734137
TI  - Increasing incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in
      the United States, 2000-2007.
AB  - Ehrlichia chaffeensis causes human monocytic ehrlichiosis, and Anaplasma
      phagocytophilum causes human granulocytic anaplasmosis. These related tick-borne
      rickettsial organisms can cause severe and fatal illness. During 2000-2007, the
      reported incidence rate of E. chaffeensis increased from 0.80 to 3.0
      cases/million persons/year. The case-fatality rate was 1.9%, and the
      hospitalization rate was 49%. During 2000-2007, the reported incidence of A.
      phagocytophilum increased from 1.4 to 3.0 cases/million persons/year. The case
      fatality rate was 0.6%, and the hospitalization rate was 36%. Rates among female
      patients were lower than among male patients for ehrlichiosis (rate ratio = 0.68)
      and anaplasmosis (rate ratio = 0.70). Most (80%) ehrlichiosis and anaplasmosis
      cases met only a probable case definition, although, use of a polymerase chain
      reaction to confirm infections increased during 2000-2007. Heightened reporting
      of these diseases will likely continue with improving recognition, changing
      surveillance practices, and appropriate application of diagnostic assays.

PMID- 21734138
TI  - Contribution of dengue fever to the burden of acute febrile illnesses in Papua
      New Guinea: an age-specific prospective study.
AB  - Malaria is a major contributor to the burden of febrile illnesses in Papua New
      Guinea (PNG). Dengue fever (DF) is likely to contribute; however, its
      epidemiology in PNG is poorly understood. We performed a prospective age
      stratified study in outpatient clinics investigating the prevalence of DF; 578
      patients were enrolled, and 317 patients with a negative rapid diagnostic test
      (RDT) for malaria were tested for dengue. Malaria was confirmed in 52% (301/578,
      95% confidence interval [CI] = 48-56%), DF was diagnosed in 8% (46/578, 95% CI =
      6-10%), and 40% (95% CI = 36-44%) had neither diagnosis. Among the 317 malaria
      RDT-negative patients, 14% (45/317, 95% CI = 10-18%) had DF. The seroprevalence
      of dengue immunoglobulin G (IgG) was 83% (204/247, 95% CI = 78-87%), and no
      dengue hemorrhagic fever was seen. This study provides good evidence for the
      first time that DF is common in PNG and is responsible for 8% of fever episodes.
      The common occurrence of DF in a population with presumed previous exposure to
      dengue is an important observation.

PMID- 21734139
TI  - Epidemiologic trends of rabies in domestic animals in southern Thailand, 1994
      2008.
AB  - Rabies and associated risk factors in dogs, cats and cattle (n = 3,454) in
      southern Thailand during 1994-2008 were evaluated by using a mixed-effect
      logistic regression model. Overall prevalence was 48%. In dogs, odds of being
      rabid were 1.7 times higher in unvaccinated dogs than in vaccinated dogs and two
      times higher in dogs with bite history than in dogs with no known bite history.
      Similarly, aggressive dogs were more likely to be rabid than non-aggressive dogs.
      In cattle, aggression, pharyngeal paralysis, hyperactivity, and depression were
      clinical signs associated with being rabid. Annual fluctuations of the species
      specific prevalence of rabies is suggestive of a positive correlation between
      canine and either feline (r = 0.60, P = 0.05) or bovine rabies (r = 0.78, P =
      0.004). Insufficient vaccination coverage led to maintenance of rabies, which
      could be easily controlled by increased vaccine coverage and public education.

PMID- 21734140
TI  - Assessment of the epidemiology and burden of measles in Southern Mozambique.
AB  - Measles has been a major killer among vaccine-preventable diseases in children <
      5 years of age in developing countries. Despite progress in global efforts to
      reduce mortality, measles remains a public health problem. Hospital-based measles
      surveillance was conducted in Manhica, Mozambique (July 2001-September 2004).
      Suspected cases and community-based controls were enrolled, and blood was
      collected for immunoglobulin M (IgM) confirmation. Two hundred fifty-three
      suspected cases and 477 controls were enrolled, with 85% (216 of 253) cases
      reported during a measles outbreak. Measles-IgM confirmation was 30% among
      suspected cases and 5% in controls. Fifty-eight percent (14 of 24) of laboratory
      confirmed cases had records indicating previous measles vaccination. Mortality
      was 3% (8 of 246) among cases and 1% among controls (6 of 426). Forty-five
      percent (33 of 74) of cases were < 24 months of age and 22% occurred in infants <
      9 months of age and were associated with a high case-fatality rate (25%). Our
      data suggest that improved diagnostics, new tools to protect infants < 9 months
      of age, and a supplemental dose of measles vaccine could assist measles control.

PMID- 21734141
TI  - Susceptibility of Vaccinia virus to chemical disinfectants.
AB  - Vaccinia virus (VACV) is the cause of bovine vaccinia (BV), an emerging zoonotic
      disease that affects dairy cows and milkers. Some chemical disinfectants have
      been used on farms affected by BV to disinfect cow teats and milkers' hands. To
      date, there is no information about the efficacy of disinfectants against VACV.
      Therefore, this study aimed to assess the virucidal activity of some active
      disinfectants commonly used in the field. Sodium hypochlorite, quaternary
      ammonium combined with chlorhexidine, and quaternary ammonium combined with
      glutaraldehyde were effective in inactivating the virus at all concentrations
      tested. Iodine and quaternary ammonium as the only active component were
      partially effective. The presence of bovine feces as organic matter and light
      decreased the effectiveness of sodium hypochlorite. These results show that an
      appropriated disinfection and asepsis of teats and hands may be helpful in the
      control and prevention of BV and other infections with VACV.

PMID- 21734142
TI  - Serologic evidence of arboviral infections among humans in Kenya.
AB  - Outbreaks of arthropod-borne viral infections occur periodically across Kenya.
      However, limited surveillance takes place during interepidemic periods. Using
      serum samples obtained from asymptomatic persons across Kenya in 2000-2004, we
      assessed (by indirect immunofluorescent assay) prevalence of IgG against yellow
      fever virus (YFV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV),
      dengue virus serotypes 1-4 (DENV1-4), and chikungunya virus (CHIKV). Older
      persons on the Indian Ocean coast were more likely to be seropositive than
      children inland: YFV = 42% versus 6%, WNV = 29% versus 6%, TBEV = 16% versus 6%,
      DENV-1 = 63% versus 9%, DENV-2 = 67% versus 7%, DENV-3 = 55% versus 6%, DENV-4 =
      44% versus 8%, and CHIKV = 37% versus 20%. Among inland samples, children in
      lowlands were more likely to be seropositive for CHIKV (42% versus 0%) than
      children in highlands. In Kenya, transmission of arboviral infection continues
      between known epidemics and remains common across the country.

PMID- 21734143
TI  - Distribution and phylogenetic comparisons of a novel mosquito flavivirus sequence
      present in Culex tarsalis Mosquitoes from western Canada with viruses isolated in
      California and Colorado.
AB  - In a previous study, a new flavivirus genome sequence was identified in Culex
      tarsalis mosquitoes obtained in Alberta, Canada and was shown to be genetically
      related to but distinct from members of the insect-specific flaviviruses.
      Nonstructural protein 5-encoding sequences amplified from Cx. tarsalis pools from
      western Canada have shown a high similarity to genome sequences of novel
      flaviviruses isolated from mosquitoes in California and Colorado. Despite wide
      distribution of this virus, designated Calbertado virus, strains demonstrate a
      high degree of nonstructural protein 5 nucleotide (> 90%) and amino acid (> 97%)
      identity. The ecology and geographic range of Calbertado virus warrants further
      study because it may potentially influence transmission of mosquito-borne
      flaviviruses, including important human pathogens such as West Nile and Saint
      Louis encephalitis viruses.

PMID- 21734144
TI  - Insect-specific flaviviruses from Culex mosquitoes in Colorado, with evidence of
      vertical transmission.
AB  - Mosquitoes were collected in Colorado during 2006 and 2007 to examine spatial and
      seasonal patterns of risk for exposure to Culex vectors and West Nile virus. We
      used universal flavivirus primers to test pools of Culex mosquitoes for viral
      RNA. This led to the detection and subsequent isolation of two insect-specific
      flaviviruses: Culex flavivirus (CxFV), which was first described from Japan, and
      a novel insect flavivirus, designated Calbertado virus (CLBOV), which has also
      been detected in California and Canada. We recorded both viruses in Cx. tarsalis
      and Cx. pipiens from Colorado. Furthermore, quantitative reverse transcription
      polymerase chain reaction (RT-PCR) revealed the presence of CxFV RNA in Cx.
      pipiens eggs and larvae from a laboratory colony established in 2005 and
      naturally infected with CxFV, suggesting vertical transmission as a means of
      viral maintenance in natural Culex populations. Finally, we present phylogenetic
      analyses of the relationships between insect-specific flaviviruses and other
      selected flaviviruses.

PMID- 21734145
TI  - West Nile and Usutu viruses in mosquitoes in Spain, 2008-2009.
AB  - West Nile virus lineage 1 (similar to the strains obtained from golden eagles in
      Spain, 2007) and Usutu virus (similar to the strains obtained from Culex pipiens
      in Spain, 2006) were detected in pools from Culex perexiguus collected in
      southern Spain in 2008 and 2009, respectively. This is the first detection and
      isolation of West Nile virus lineage 1 from mosquitoes in Spain.

PMID- 21734146
TI  - Vector competence of New Zealand mosquitoes for selected arboviruses.
AB  - New Zealand (NZ) historically has been free of arboviral activity with the
      exception of Whataroa virus (Togaviridae: Alphavirus), which is established in
      bird populations and is transmitted by local mosquitoes. This naive situation is
      threatened by global warming, invasive mosquitoes, and tourism. To determine the
      threat of selected medically important arboviruses to NZ, vector competence
      assays were conducted using field collected endemic and introduced mosquito
      species. Four alphaviruses (Togaviridae): Barmah Forest virus, Chikungunya virus,
      Ross River virus, and Sindbis virus, and five flaviviruses (Flaviviridae): Dengue
      virus 2, Japanese encephalitis virus, Murray Valley encephalitis virus, West Nile
      virus, and Yellow fever virus were evaluated. Results indicate some NZ mosquito
      species are highly competent vectors of selected arboviruses, particularly
      alphaviruses, and may pose a threat were one of these arboviruses introduced at a
      time when the vector was prevalent and the climatic conditions favorable for
      virus transmission.

PMID- 21734147
TI  - Abdominal computed tomography scan: a useful diagnosis tool for early and delayed
      splenic complications in malaria.

PMID- 21734148
TI  - Does casein kinase II phosphorylation of Maf1 trigger RNA polymerase III
      activation?

PMID- 21734149
TI  - Survival of starving yeast is correlated with oxidative stress response and
      nonrespiratory mitochondrial function.
AB  - Survival of yeast during starvation has been shown to depend on the nature of the
      missing nutrient(s). In general, starvation for "natural" nutrients such as
      sources of carbon, phosphate, nitrogen, or sulfate results in low death rates,
      whereas starvation for amino acids or other metabolites in auxotrophic mutants
      results in rapid loss of viability. Here we characterized phenotype, gene
      expression, and metabolite abundance during starvation for methionine. Some
      methionine auxotrophs (those with blocks in the biosynthetic pathway) respond to
      methionine starvation like yeast starving for natural nutrients such as phosphate
      or sulfate: they undergo a uniform cell cycle arrest, conserve glucose, and
      survive. In contrast, methionine auxotrophs with defects in the transcription
      factors Met31p and Met32p respond poorly, like other auxotrophs. We combined
      physiological and gene expression data from a variety of nutrient starvations (in
      both respiratory competent and incompetent cells) to show that successful
      starvation response is correlated with expression of genes encoding oxidative
      stress response and nonrespiratory mitochondrial functions, but not respiration
      per se.

PMID- 21734150
TI  - Knocking out the door to tunicamycin entry.

PMID- 21734151
TI  - Mutation of the conserved polyadenosine RNA binding protein, ZC3H14/dNab2,
      impairs neural function in Drosophila and humans.
AB  - Here we report a human intellectual disability disease locus on chromosome
      14q31.3 corresponding to mutation of the ZC3H14 gene that encodes a conserved
      polyadenosine RNA binding protein. We identify ZC3H14 mRNA transcripts in the
      human central nervous system, and we find that rodent ZC3H14 protein is expressed
      in hippocampal neurons and colocalizes with poly(A) RNA in neuronal cell bodies.
      A Drosophila melanogaster model of this disease created by mutation of the gene
      encoding the ZC3H14 ortholog dNab2, which also binds polyadenosine RNA, reveals
      that dNab2 is essential for development and required in neurons for normal
      locomotion and flight. Biochemical and genetic data indicate that dNab2 restricts
      bulk poly(A) tail length in vivo, suggesting that this function may underlie its
      role in development and disease. These studies reveal a conserved requirement for
      ZC3H14/dNab2 in the metazoan nervous system and identify a poly(A) RNA binding
      protein associated with a human brain disorder.

PMID- 21734152
TI  - Defining the quantitative limits of intravital two-photon lymphocyte tracking.
AB  - Two-photon microscopy has substantially advanced our understanding of cellular
      dynamics in the immune system. Cell migration can now be imaged in real time in
      the living animal. Strikingly, the migration of naive lymphocytes in secondary
      lymphoid tissue appears predominantly random. It is unclear, however, whether
      directed migration may escape detection in this random background. Using a
      combination of mathematical modeling and experimental data, we investigate the
      extent to which modern two-photon imaging can rule out biologically relevant
      directed migration. For naive T cells migrating in uninfected lymph nodes (LNs)
      at average 3D speeds of around 18 MUm/min, we rule out uniform directed migration
      of more than 1.7 MUm/min at the 95% confidence level, confirming that T cell
      migration is indeed mostly random on a timescale of minutes. To investigate
      whether this finding still holds for longer timescales, we use a 3D simulation of
      the naive T cell LN transit. A pure random walk predicts a transit time of around
      16 h, which is in good agreement with experimental results. A directional bias of
      only 0.5 MUm/min-less than 3% of the cell speed-would already accelerate the
      transit twofold. These results jointly strengthen the random walk analogy for
      naive T cell migration in LNs, but they also emphasize that very small deviations
      from random migration can still be important. Our methods are applicable to cells
      of any type and can be used to reanalyze existing datasets.

PMID- 21734153
TI  - Changes in ranges of large ocean fish.

PMID- 21734154
TI  - The microRNA contribution to learning and memory.
AB  - Learning and memory refer to an animal's ability to respond adequately to
      environmental signals that may be negative (aversive learning) or positive
      (appetitive learning) in nature. The extremely elaborate connectivity network of
      neurons in the brain is capable of governing animals' reactions (e.g., by
      enhancing or weakening single or multiple synapses). Such circuit plasticity is
      largely believed to be the very essence of memory formation. It has been
      suggested that long-term memory, in contrast to short-term memory, requires de
      novo protein synthesis and can be prevented by protein synthesis inhibitors. The
      local protein translation in dendrites allows neurons to selectively rebuild only
      those synapses that have been activated. However, substrates of protein synthesis
      (i.e., mRNA) have to be kept suppressed until they are needed. MicroRNAs--short,
      non-protein-coding RNA regulatory sequences that guide an RNA--induced silencing
      complex to target mRNAs-seem to be perfect candidates in fulfilling this function
      in neurons. In this article, the authors discuss the recently recognized role of
      microRNAs as regulators of memory formation and endurance.

PMID- 21734156
TI  - Trimodal gadolinium-gold microcapsules containing pancreatic islet cells restore
      normoglycemia in diabetic mice and can be tracked by using US, CT, and positive
      contrast MR imaging.
AB  - PURPOSE: To develop microcapsules that immunoprotect pancreatic islet cells for
      treatment of type I diabetes and enable multimodal cellular imaging of
      transplanted islet cells. MATERIALS AND METHODS: All animal experiments were
      approved by the institutional animal care and use committee. Gold nanoparticles
      functionalized with DTDTPA (dithiolated diethylenetriaminepentaacetic
      acid):gadolinium chelates (GG) were coencapsulated with pancreatic islet cells by
      using protamine sulfate as a clinical-grade alginate cross linker. Conventional
      poly-l-lysine-cross-linked microcapsules and unencapsulated islets were included
      as controls. The viability and glucose responsiveness of islet cells were
      assessed in vitro, and in vivo insulin (C-peptide) secretion was monitored for 6
      weeks in (streptozotocin-induced) diabetic mice with (n = 7) or without (n = 8)
      intraabdominally engrafted islet cells. Five nondiabetic mice were included as
      controls. Differences between samples were calculated by using a nonparametric
      Wilcoxon Mann-Whitney method. To adjust for multiple comparisons, a significance
      level of P < .01 was chosen. Generalized estimating equations were used to model
      cell function over time. Three mice with engrafted capsules were imaged in vivo
      with high-field-strength (9.4-T) magnetic resonance (MR) imaging, micro-computed
      tomography (CT), and 40-MHz ultrasonography (US). RESULTS: Encapsulated human
      pancreatic islets were functional in vitro for at least 2 weeks after
      encapsulation. Blood glucose levels in the diabetic mice transplanted with GG
      labeled encapsulated mouse betaTC6 insulinoma cells returned to normal within 1
      week after transplantation, and normoglycemia was sustained for at least 6 weeks
      without the use of immunosuppressive drugs. GG microcapsules could be readily
      visualized with positive-contrast high-field-strength MR imaging, micro-CT, and
      US both in vitro and in vivo. CONCLUSION: Cell encapsulation with GG provides a
      means of trimodal noninvasive tracking of engrafted cells.

PMID- 21734157
TI  - Late stage complicated atheroma in low-grade stenotic carotid disease: MR imaging
      depiction--prevalence and risk factors.
AB  - PURPOSE: To determine if complicated plaque can be found by using magnetic
      resonance (MR) imaging-depicted intraplaque hemorrhage (IPH), even among
      symptomatic patients with low-grade (<=50%) carotid stenosis. MATERIALS AND
      METHODS: The institutional ethics review board approved this retrospective study
      and waived requirements for written informed consent. Symptomatic patients with
      bilateral 0%-50% carotid stenosis referred for carotid MR imaging were
      considered. Risk factors (age, sex, hypertension, diabetes, hyperlipidemia,
      myocardial infarction, atrial fibrillation, smoking, coronary artery disease, and
      cerebrovascular disease), medications (antihypertensive drugs, diabetes drugs,
      statins, and aspirin), and the brain side causing symptoms were recorded. MR
      depicted IPH prevalence in the carotid arteries ipsilateral and contralateral to
      the symptomatic side was compared by using the Fisher exact test. Multivariable
      regression was used to compare the MR-depicted IPH prevalence, while adjusting
      for risk factors and medications. RESULTS: A total of 217 patients (434 carotid
      arteries) were included. MR-depicted IPH was found in 13% (31 of 233) of carotid
      arteries ipsilateral and 7% (14 of 201) of arteries contralateral to symptoms (P
      < .05). Male sex (P < .05) and increasing age (P < .05) were associated with MR
      depicted IPH after controlling for risk factors and medications. CONCLUSION:
      Complicated carotid atheroma can be found among symptomatic patients with low
      grade (<=50%) stenosis, and this is associated with male sex and increasing age.
      MR-depicted IPH may be useful to stratify risk for patients with low-grade
      carotid stenosis.

PMID- 21734158
TI  - Hepatic arterial stenosis assessed with doppler US after liver transplantation:
      frequent false-positive diagnoses with tardus parvus waveform and value of adding
      optimal peak systolic velocity cutoff.
AB  - PURPOSE: To evaluate the utility of the tardus parvus waveform of the hepatic
      artery at Doppler ultrasonography (US) in the diagnosis of hepatic arterial
      stenosis in liver transplant (LT) recipients and determine whether the accuracy
      of such a diagnosis is enhanced by including an optimal peak systolic velocity
      (PSV) cutoff. MATERIALS AND METHODS: This retrospective study was institutional
      review board approved; the requirement for informed consent was waived. The
      authors identified 361 LT recipients (267 male, 94 female) who underwent Doppler
      US and either computed tomography (CT) or angiography, with an interval between
      these examinations of less than 1 week. At Doppler US, tardus parvus pattern was
      defined as a waveform with a resistive index (RI) of less than 0.5 and a systolic
      acceleration time longer than 0.08 second. At CT or angiography, patients were
      assigned to the hepatic arterial stenosis (>=50% vessel narrowing) or nonstenosis
      group. The capability of the tardus parvus pattern to facilitate the diagnosis of
      hepatic arterial stenosis was calculated. The difference in PSV between the true-
      and false-positive tardus parvus patterns was evaluated. Receiver operating
      characteristic (ROC) analysis was performed to determine the optimal cutoff PSV
      for diagnosing hepatic arterial stenosis. The capability of the tardus parvus
      pattern and an optimal PSV cutoff in the diagnosis of hepatic arterial stenosis
      was determined. RESULTS: Sixty transplant recipients had the tardus parvus
      pattern at Doppler US. The sensitivity, specificity, and positive predictive
      value (PPV) of the tardus parvus pattern were 72% (23 of 32 LT recipients), 88.8%
      (292 of 329 LT recipients), and 38% (23 of 60 LT recipients), respectively. The
      false-positive rate was 11.2% (37 of 329 LT recipients). ROC analysis revealed an
      optimal PSV cutoff of less than or equal to 48 cm/sec for diagnosing hepatic
      arterial stenosis. The combination of the tardus parvus pattern and a PSV cutoff
      of less than or equal to 48 cm/sec improved specificity to 99.1% (326 of 329 LT
      recipients) and the PPV to 88% (22 of 25 LT recipients), thereby reducing the
      false-positive rate to 1% (three of 329 LT recipients) while slightly decreasing
      the sensitivity to 69% (22 of 32 LT recipients). CONCLUSION: Use of the tardus
      parvus waveform of the hepatic artery resulted in a low PPV and a high false
      positive rate. However, the combination of the tardus parvus pattern and an
      optimal PSV cutoff greatly improved the PPV and reduced the false-positive rate
      in the diagnosis of hepatic arterial stenosis.

PMID- 21734159
TI  - Real-time FDG PET guidance during biopsies and radiofrequency ablation using
      multimodality fusion with electromagnetic navigation.
AB  - PURPOSE: To assess the feasibility of combined electromagnetic device tracking
      and computed tomography (CT)/ultrasonography (US)/fluorine 18 fluorodeoxyglucose
      (FDG) positron emission tomography (PET) fusion for real-time feedback during
      percutaneous and intraoperative biopsies and hepatic radiofrequency (RF)
      ablation. MATERIALS AND METHODS: In this HIPAA-compliant, institutional review
      board-approved prospective study with written informed consent, 25 patients (17
      men, eight women) underwent 33 percutaneous and three intraoperative biopsies of
      36 FDG-avid targets between November 2007 and August 2010. One patient underwent
      biopsy and RF ablation of an FDG-avid hepatic focus. Targets demonstrated
      heterogeneous FDG uptake or were not well seen or were totally inapparent at
      conventional imaging. Preprocedural FDG PET scans were rigidly registered through
      a semiautomatic method to intraprocedural CT scans. Coaxial biopsy needle
      introducer tips and RF ablation electrode guider needle tips containing
      electromagnetic sensor coils were spatially tracked through an electromagnetic
      field generator. Real-time US scans were registered through a fiducial-based
      method, allowing US scans to be fused with intraprocedural CT and preacquired FDG
      PET scans. A visual display of US/CT image fusion with overlaid coregistered FDG
      PET targets was used for guidance; navigation software enabled real-time biopsy
      needle and needle electrode navigation and feedback. RESULTS: Successful fusion
      of real-time US to coregistered CT and FDG PET scans was achieved in all
      patients. Thirty-one of 36 biopsies were diagnostic (malignancy in 18 cases,
      benign processes in 13 cases). RF ablation resulted in resolution of targeted FDG
      avidity, with no local treatment failure during short follow-up (56 days).
      CONCLUSION: Combined electromagnetic device tracking and image fusion with real
      time feedback may facilitate biopsies and ablations of focal FDG PET
      abnormalities that would be challenging with conventional image guidance.

PMID- 21734160
TI  - In vivo detection of acinar microstructural changes in early emphysema with (3)He
      lung morphometry.
AB  - PURPOSE: To quantitatively characterize early emphysematous changes in the lung
      microstructure of current and former smokers with noninvasive helium 3 ((3)He)
      lung morphometry and to compare these results with the clinical standards,
      pulmonary function testing (PFT) and low-dose computed tomography (CT). MATERIALS
      AND METHODS: This study was approved by the local institutional review board, and
      all subjects provided informed consent. Thirty current and former smokers, each
      with a minimum 30-pack-year smoking history and mild or no abnormalities at PFT,
      underwent (3)He lung morphometry. This technique is based on diffusion MR imaging
      with hyperpolarized (3)He gas and yields quantitative localized in vivo
      measurements of acinar airway geometric parameters, such as airway radii,
      alveolar depth, and number of alveoli per unit lung volume. These measurements
      enable calculation of standard morphometric characteristics, such as mean linear
      intercept and surface-to-volume ratio. RESULTS: Noninvasive (3)He lung
      morphometry was used to detect alterations in acinar structure in smokers with
      normal PFT findings. When compared with smokers with the largest forced
      expiratory volume in 1 second (FEV(1)) to forced vital capacity (FVC) ratio,
      those with chronic obstructive pulmonary disease had significantly reduced
      alveolar depth (0.07 mm vs 0.13 mm) and enlarged acinar ducts (0.36 mm vs 0.3
      mm). The mean alveolar geometry measurements in the healthiest subjects were in
      excellent quantitative agreement with literature values obtained by using
      invasive techniques (acinar duct radius, 0.3 mm; alveolar depth, 0.14 mm at 1 L
      above functional residual capacity). (3)He lung morphometry depicted greater
      abnormalities than did PFT and CT. No adverse events were associated with
      inhalation of (3)He gas. CONCLUSION: (3)He lung morphometry yields valuable
      noninvasive insight into early emphysematous changes in alveolar geometry with
      increased sensitivity compared with conventional techniques.

PMID- 21734161
TI  - In and out of a daydream: attachment orientations, daily couple interactions, and
      sexual fantasies.
AB  - In this study, the authors examined the contribution of attachment orientations
      to the content of daily sexual fantasies. The two partners of 48 couples
      independently reported on their attachment orientations and provided daily
      reports on relationship interactions and sexual fantasies for a period of 21
      days. Results showed that attachment anxiety was associated with wishes for
      intimacy and representations of others as more affectionate in sexual fantasies.
      Conversely, avoidant attachment was associated with avoidance-related wishes and
      representations of the self and others as more aggressive and alienated. Negative
      couple interactions increased habitual attachment-related wishes and self
      representations. Specifically, during days characterized by negative couple
      interactions (relationship-damaging behaviors), attachment anxiety was associated
      with portrayal of the self as more helpless and avoidant attachment was
      associated with the expression of more avoidant wishes and portrayal of the self
      as less helpless. The discussion focuses on the manifestations of attachment
      related interpersonal goals in sexual fantasies.

PMID- 21734162
TI  - Cognitive and affective matching effects in persuasion: an amplification
      perspective.
AB  - Past research suggests that cognitive and affective attitudes are more open to
      change toward cognitive and affective (i.e., matched) persuasive attacks,
      respectively. The present research investigates how attitude certainty influences
      this openness. Although an extensive literature suggests that certainty generally
      reduces an attitude's openness to change, the authors explore the possibility
      that certainty might increase an attitude's openness to change in the context of
      affective or cognitive appeals. Based on the recently proposed amplification
      hypothesis, the authors posit that high (vs. low) attitude certainty will boost
      the resistance of attitudes to mismatched attacks (e.g., affective attitudes
      attacked by cognitive messages) but boost the openness of attitudes to matched
      attacks (e.g., affective attitudes attacked by affective messages). Two
      experiments provide support for this hypothesis. Implications for increasing the
      openness of attitudes to both matched and mismatched attacks are discussed.

PMID- 21734163
TI  - Counterfactual seeking: The scenic overlook of the road not taken.
AB  - Decision makers faced with an opportunity to learn the outcome of a foregone
      alternative must balance anticipated regret, should that information be
      unfavorable, with the potential benefits of this information in reducing
      experienced regret. Counterfactual seeking, the choice to learn more about
      foregone alternatives, may be a functional, regret-regulating strategy for
      individuals already experiencing regret. Counterfactual seeking increases in
      response to dissatisfying outcomes (Studies 1 and 2). Counterfactual seeking is
      generally able to reduce dissatisfaction (Study 2), regardless of whether
      individuals personally chose to view this information or were randomly assigned
      to do so (Study 3). Moreover, both imaginative (vs. factual) thoughts about the
      foregone option and upward (vs. downward) counterfactual thoughts play a role in
      this improvement in satisfaction (Study 4). Regret thus has a complex influence
      in how individuals engage with counterfactual information.

PMID- 21734164
TI  - Acknowledging the skeletons in our closet: the effect of group affirmation on
      collective guilt, collective shame, and reparatory attitudes.
AB  - Just as with threats to personal identity, people defend against social identity
      threats. In the context of intergroup injustice, such defensiveness undercuts
      collective guilt and its prosocial consequences. The current research examines
      whether group affirmation allows perpetrator groups to disarm threat without
      undermining guilt. In Study 1, men accepted greater guilt for gender inequality
      after affirming the ingroup. Given the distinction between collective guilt and
      collective shame, Studies 2-4 assessed both emotions and revealed that Canadians
      accepted greater guilt and shame over the mistreatment of Aboriginals following
      group affirmation. In Study 3, group affirmation also moderated the relation of
      each emotion with reparatory attitudes. When controlling for each other,
      collective shame predicted compensation in a nonaffirmation control condition
      whereas guilt predicted compensation once identity threat had been disarmed by
      group affirmation. In Study 4, the effect of group affirmation on the collective
      emotions was mediated by defensive appraisals of the injustice.

PMID- 21734165
TI  - Endometrial cancer.

PMID- 21734167
TI  - Hopes for a health legacy from the Olympic games should focus on community not
      sport, says expert.

PMID- 21734168
TI  - Time to get smart about IT.

PMID- 21734169
TI  - Seeming virtuous on chronic diseases.

PMID- 21734171
TI  - Should our children be sitting comfortably in school?

PMID- 21734172
TI  - A 22 year old man with acute genital oedema and a swollen ankle.

PMID- 21734173
TI  - Reengineering translational science: the time is right.
AB  - Despite dramatic advances in the molecular pathogenesis of disease, translation
      of basic biomedical research into safe and effective clinical applications
      remains a slow, expensive, and failure-prone endeavor. To pursue opportunities
      for disruptive translational innovation, the U.S. National Institutes of Health
      (NIH) intends to establish a new entity, the National Center for Advancing
      Translational Sciences (NCATS). The mission of NCATS is to catalyze the
      generation of innovative methods and technologies that will enhance the
      development, testing, and implementation of diagnostics and therapeutics across a
      wide range of diseases and conditions. The new center's activities will
      complement, and not compete with, translational research being carried out at NIH
      and elsewhere in the public and private sectors.

PMID- 21734174
TI  - Development of newborn and infant vaccines.
AB  - Vaccines for early-life immunization are a crucial biomedical intervention to
      reduce global morbidity and mortality, yet their developmental path has been
      largely ad hoc, empiric, and inconsistent. Immune responses of human newborns and
      infants are distinct and cannot be predicted from those of human adults or animal
      models. Therefore, understanding and modeling age-specific human immune responses
      will be vital to the rational design and development of safe and effective
      vaccines for newborns and infants.

PMID- 21734175
TI  - Optimization of dosing for EGFR-mutant non-small cell lung cancer with
      evolutionary cancer modeling.
AB  - Non-small cell lung cancers (NSCLCs) that harbor mutations within the epidermal
      growth factor receptor (EGFR) gene are sensitive to the tyrosine kinase
      inhibitors (TKIs) gefitinib and erlotinib. Unfortunately, all patients treated
      with these drugs will acquire resistance, most commonly as a result of a
      secondary mutation within EGFR (T790M). Because both drugs were developed to
      target wild-type EGFR, we hypothesized that current dosing schedules were not
      optimized for mutant EGFR or to prevent resistance. To investigate this further,
      we developed isogenic TKI-sensitive and TKI-resistant pairs of cell lines that
      mimic the behavior of human tumors. We determined that the drug-sensitive and
      drug-resistant EGFR-mutant cells exhibited differential growth kinetics, with the
      drug-resistant cells showing slower growth. We incorporated these data into
      evolutionary mathematical cancer models with constraints derived from clinical
      data sets. This modeling predicted alternative therapeutic strategies that could
      prolong the clinical benefit of TKIs against EGFR-mutant NSCLCs by delaying the
      development of resistance.

PMID- 21734176
TI  - CXCL5 mediates UVB irradiation-induced pain.
AB  - Many persistent pain states (pain lasting for hours, days, or longer) are poorly
      treated because of the limitations of existing therapies. Analgesics such as
      nonsteroidal anti-inflammatory drugs and opioids often provide incomplete pain
      relief and prolonged use results in the development of severe side effects.
      Identification of the key mediators of various types of pain could improve such
      therapies. Here, we tested the hypothesis that hitherto unrecognized cytokines
      and chemokines might act as mediators in inflammatory pain. We used ultraviolet B
      (UVB) irradiation to induce persistent, abnormal sensitivity to pain in humans
      and rats. The expression of more than 90 different inflammatory mediators was
      measured in treated skin at the peak of UVB-induced hypersensitivity with custom
      made polymerase chain reaction arrays. There was a significant positive
      correlation in the overall expression profiles between the two species. The
      expression of several genes [interleukin-1beta (IL-1beta), IL-6, and
      cyclooxygenase-2 (COX-2)], previously shown to contribute to pain
      hypersensitivity, was significantly increased after UVB exposure, and there was
      dysregulation of several chemokines (CCL2, CCL3, CCL4, CCL7, CCL11, CXCL1, CXCL2,
      CXCL4, CXCL7, and CXCL8). Among the genes measured, CXCL5 was induced to the
      greatest extent by UVB treatment in human skin; when injected into the skin of
      rats, CXCL5 recapitulated the mechanical hypersensitivity caused by UVB
      irradiation. This hypersensitivity was associated with the infiltration of
      neutrophils and macrophages into the dermis, and neutralizing the effects of
      CXCL5 attenuated the abnormal pain-like behavior. Our findings demonstrate that
      the chemokine CXCL5 is a peripheral mediator of UVB-induced inflammatory pain,
      likely in humans as well as rats.

PMID- 21734177
TI  - Deep sequencing of the human TCRgamma and TCRbeta repertoires suggests that
      TCRbeta rearranges after alphabeta and gammadelta T cell commitment.
AB  - T lymphocytes respond to a broad array of pathogens with the combinatorial
      diversity of the T cell receptor (TCR). This adaptive response is possible
      because of the unique structure of the TCR, which is composed of two chains,
      either alphabeta or gammadelta, that undergo genetic rearrangement in the thymus.
      alphabeta and gammadelta T cells are functionally distinct within the host but
      are derived from a common multipotent precursor. The canonical model for T cell
      lineage commitment assumes that the gamma, delta, and beta chains rearrange
      before alphabeta or gammadelta T cell commitment. To test the standard model in
      humans, we used high-throughput sequencing to catalog millions of TCRgamma and
      TCRbeta chains from peripheral blood alphabeta and gammadelta T cells from three
      unrelated individuals. Almost all sampled alphabeta and gammadelta T cells had
      rearranged TCRgamma sequences. Although sampled alphabeta T cells had a diverse
      repertoire of rearranged TCRbeta chains, less than 4% of gammadelta T cells in
      peripheral blood had a rearranged TCRbeta chain. Our data suggest that TCRgamma
      rearranges in all T lymphocytes, consistent with TCRgamma rearranging before T
      cell lineage commitment. However, rearrangement of the TCRbeta locus appears to
      be restricted after T cell precursors commit to the alphabeta T cell lineage.
      Indeed, in T cell leukemias and lymphomas, TCRgamma is almost always rearranged
      and TCRbeta is only rearranged in a subset of cancers. Because high-throughput
      sequencing of TCRs is translated into the clinic for monitoring minimal residual
      for leukemia/lymphoma, our data suggest the sequencing target should be TCRgamma.

PMID- 21734178
TI  - Cervical arterial dissections due to segmental mediolytic arteriopathy.

PMID- 21734179
TI  - A randomized trial of 4-aminopyridine in EA2 and related familial episodic
      ataxias.
AB  - OBJECTIVE: The therapeutic effects of 4-aminopyridine (4AP) were investigated in
      a randomized, double-blind, crossover trial in 10 subjects with familial episodic
      ataxia with nystagmus. METHODS: After randomization, placebo or 4AP (5 mg 3 times
      daily) was administered for 2 3-month-long treatment periods separated by a 1
      month-long washout period. The primary outcome measure was the number of ataxia
      attacks per month; the secondary outcome measures were the attack duration and
      patient-reported quality of life (Vestibular Disorders Activities of Daily Living
      Scale [VDADL]). Nonparametric tests and a random-effects model were used for
      statistical analysis. RESULTS: The diagnosis of episodic ataxia type 2 (EA2) was
      genetically confirmed in 7 subjects. Patients receiving placebo had a median
      monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of
      1.65 (p = 0.03). Median monthly attack duration decreased from 13.65 hours with
      placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to
      1.50 (p = 0.02). 4AP was well-tolerated. CONCLUSIONS: This controlled trial on
      EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases
      attack frequency and improves quality of life. LEVEL OF EVIDENCE: This crossover
      study provides Class II evidence that 4AP decreases attack frequency and improves
      the patient-reported quality of life in patients with episodic ataxia and related
      familial ataxias.

PMID- 21734180
TI  - Morphometry of dermal nerve fibers in human skin.
AB  - OBJECTIVE: We aimed to assess the innervation density of dermal nerves in human
      skin biopsies by bright-field immunohistochemistry. METHODS: The size of dermal
      area where nerve length was quantified was validated in 30 skin biopsy sections
      (5 controls and 5 patients with small-fiber neuropathy [SFN]). It was obtained
      dividing an area of 200-MUm depth from the dermal-epidermal junction into 4 equal
      portions. The length of dermal nerves (DNFL) was measured into 150 sections (25
      controls and 25 patients with SFN) and values per millimeter of epidermis
      (DNFL/mm) and dermal area (DNFL/mm2) were obtained. Age- and gender-matched
      normative values of intraepidermal nerve fiber (IENF) density were used as gold
      standard to calculate the performance of dermal nerve morphometry. RESULTS:
      Patients showed significantly lower DNFL (1.96 mm +/- 0.96 SD), DNFL/mm (0.65 +/-
      0.29 SD), and DNFL/mm2 (3.75 +/- 1.7 SD) than controls (DNFL 3.52 mm +/- 1.31 SD,
      5th percentile 2.05; DNFL/mm 1.25 +/- 0.39, 5th percentile 0.71; DNFL/mm2 7.07 +/
      2.41 SD, 5th percentile 3.95). Sensitivity, specificity, and percentage of
      individuals correctly classified were 75.8%, 73.9%, and 74.8% for DNFL, 75%, 80%,
      and 77.7% for DNFL/mm, and 75.8%, 80.2%, and 78.1% for DNFL/mm2. Receiver
      operator characteristic area analysis confirmed the excellent discrimination (0.8
      0.9) between patients and controls. Dermal nerve morphometry significantly
      correlated with IENF density. Spearman rank correlation demonstrated good
      agreement for interobserver analysis (0.87-0.89), and between DNFL and IENF
      densities (0.71-0.73; p < 0.0001). CONCLUSIONS: We provided a reliable method to
      quantify the innervation density of dermal nerves that might improve the
      diagnostic yield of skin biopsy.

PMID- 21734181
TI  - Progressive multifocal leukoencephalopathy in a patient without immunodeficiency.

PMID- 21734182
TI  - GBA-associated PD presents with nonmotor characteristics.
AB  - OBJECTIVE: To evaluate whether there exists distinct characteristics in
      glucocerebrosidase (GBA)-associated Parkinson disease (PD) with regard to motor
      and nonmotor symptoms as well as imaging characteristics assessed by transcranial
      sonography (TCS). METHODS: Twenty patients with PD with heterozygous GBA
      mutations (N370S, L444P) (GBA-PD) in comparison to 20 patients with sporadic PD
      negative for GBA mutations (sPD) were included. We assessed motor impairment with
      the Unified Parkinson's Disease Rating Scale-III. Nonmotor symptoms were
      evaluated using the Montreal Cognitive Assessment, Neuropsychiatric Inventory,
      revised form of the Beck Depression Inventory, Parkinson Disease Sleep Scale,
      Sniffin' Sticks, and Unified Multiple System Atrophy Rating Scale items 9-12. TCS
      imaging was used to detect morphologic characteristics. RESULTS: Patients with
      GBA-PD more often had a variety of nonmotor symptoms, namely dementia,
      neuropsychiatric disturbances, and autonomic dysfunction, and had more severe
      cases, than patients with sPD. They also demonstrated a higher prevalence of a
      reduced echogenicity of the brainstem raphe assessed by TCS. CONCLUSIONS:
      Especially nonmotor symptoms seem to be very common in GBA-PD. Further studies
      are needed to validate these observations in order to better understand the
      pathogenesis of GBA-PD and develop specific therapeutic concepts.

PMID- 21734183
TI  - Functional changes in Duchenne muscular dystrophy: a 12-month longitudinal cohort
      study.
AB  - OBJECTIVE: The aim of the study was to assess different outcome measures in a
      cohort of ambulant boys with Duchenne muscular dystrophy (DMD) over 12 months in
      order to establish the spectrum of possible changes in relation to age and
      steroid treatment. METHODS: The study is a longitudinal multicentric cohort
      study. A total of 106 ambulant patients with DMD were assessed using the 6-minute
      walk test (6MWT) and North Star Ambulatory Assessment (NSAA) at baseline and 12
      months. Clinical data including age and steroid treatment were collected.
      RESULTS: During the 12 months of the study, we observed a mean decline of 25.8
      meters in the 6MWT with a SD of 74.3 meters. On NSAA, the mean decline was 2.2
      points with a SD of 3.7. Not all the boys with DMD in our cohort showed a decline
      over the 12 months, with young boys showing some improvement in their 6MWT and
      NSAA scores up to the age of 7. NSAA and the 6MWT had the highest correlation (r
      = 0.52, p < 0.001). CONCLUSIONS: This study provides longitudinal data of NSAA
      and 6MWT over a 12-month period. These data can be useful when designing a
      clinical trial.

PMID- 21734184
TI  - Breastfeeding is not related to postpartum relapses in multiple sclerosis.
AB  - OBJECTIVE: To assess the relationship between breastfeeding and risk of puerperal
      relapses in a large cohort of patients with multiple sclerosis (MS). METHODS: We
      prospectively followed-up pregnancies occurring between 2002 and 2008 in women
      with MS, recruited from 21 Italian MS centers, and gathered data on breastfeeding
      through a standardized interview. The risk of relapses after delivery was
      assessed using the Cox regression analysis. RESULTS: A total of 302 out of 423
      pregnancies in 298 women resulted in full-term deliveries. Patients were followed
      up for at least 1 year after delivery. The time-dependent profile of the relapse
      rate before, during, and after pregnancy did not differ between patients who
      breastfed and patients who did not. In the multivariate analysis, adjusting for
      age at onset, age at pregnancy, disease duration, disability level, and relapses
      in the year prior to pregnancy and during pregnancy, treatment with disease
      modifying drugs (DMDs), and exposure to toxics, the only significant predictors
      of postpartum relapses were relapses in the year before pregnancy (hazard ratio
      [HR] = 1.5; 95%confidence interval [CI] 1.3-1.9; p < 0.001) and during pregnancy
      (HR = 2.2; 95% CI 1.5-3.3; p < 0.001). CONCLUSIONS: In our sample, postpartum
      relapses were predicted only by relapses before and during pregnancy. Therefore,
      the reported association between breastfeeding and a lower risk of postpartum
      relapses may simply reflect different patient behavior, biased by the disease
      activity. Our results can assist neurologists facing the breastfeeding issue in
      mother counseling and shared decision-making. Especially, among patients with
      high risk of postpartum relapses, breastfeeding may not be feasible and early
      postpartum treatment should be an option.

PMID- 21734185
TI  - Deficiency of MGAT2 increases energy expenditure without high-fat feeding and
      protects genetically obese mice from excessive weight gain.
AB  - Acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) is thought to be crucial for
      dietary fat absorption. Indeed, mice lacking the enzyme (Mogat2(-/-)) are
      resistant to obesity and other metabolic disorders induced by high-fat feeding.
      However, these mice absorb normal quantities of fat. To explore whether a high
      level of dietary fat is an essential part of the underlying mechanism(s), we
      examined metabolic responses of Mogat2(-/-) mice to diets containing varying
      levels of fat. Mogat2(-/-) mice exhibited 10-15% increases in energy expenditure
      compared with wild-type littermates; although high levels of dietary fat
      exacerbated the effect, this phenotype was expressed even on a fat-free diet.
      When deprived of food, Mogat2(-/-) mice expended energy and lost weight like wild
      type controls. To determine whether MGAT2 deficiency protects against obesity in
      the absence of high-fat feeding, we crossed Mogat2(-/-) mice with genetically
      obese Agouti mice. MGAT2 deficiency increased energy expenditure and prevented
      these mice from gaining excess weight. Our results suggest that MGAT2 modulates
      energy expenditure through multiple mechanisms, including one independent of
      dietary fat; these findings also raise the prospect of inhibiting MGAT2 as a
      strategy for combating obesity and related metabolic disorders resulting from
      excessive calorie intake.

PMID- 21734187
TI  - Lysosomal action of intracrine angiotensin II. Focus on "Intracellular
      angiotensin II activates rat myometrium".

PMID- 21734186
TI  - Implication of microRNAs in atrial natriuretic peptide and nitric oxide signaling
      in vascular smooth muscle cells.
AB  - MicroRNAs (miRs) are endogenous small RNA molecules that suppress gene expression
      by binding to complementary sequences in the 3' untranslated regions of their
      target genes. miRs have been implicated in many diseases, including heart
      failure, ischemic heart disease, hypertension, cardiac hypertrophy, and cancers.
      Nitric oxide (NO) and atrial natriuretic peptide (ANP) are potent vasorelaxants
      whose actions are mediated through receptor guanylyl cyclases and cGMP-dependent
      protein kinase. The present study examines miRs in signaling by ANP and NO in
      vascular smooth muscle cells. miR microarray analysis was performed on human
      vascular smooth muscle cells (HVSMC) treated with ANP (10 nM, 4 h) and S-nitroso
      N-acetylpenicillamine (SNAP) (100 MUM, 4 h), a NO donor. Twenty-two shared miRs
      were upregulated, and 21 shared miRs were downregulated, by both ANP and SNAP (P
      < 0.05). Expression levels of four miRs (miRs-21, -26b, -98, and -1826), which
      had the greatest change in expression, as determined by microarray analysis, were
      confirmed by quantitative RT-PCR. Rp-8-Br-PET-cGMPS, a cGMP-dependent protein
      kinase-specific inhibitor, blocked the regulation of these miRs by ANP and SNAP.
      8-bromo-cGMP mimicked the effect of ANP and SNAP on their expression. miR-21 was
      shown to inhibit HVSMC contraction in collagen gel lattice contraction assays. We
      also identified by computational algorithms and confirmed by Western blot
      analysis new intracellular targets of miR-21, i.e., cofilin-2 and myosin
      phosphatase and Rho interacting protein. Transfection with pre-miR-21 contracted
      cells and ANP and SNAP blocked miR-21-induced HVSMC contraction. Transfection
      with anti-miR-21 inhibitor reduced contractility of HVSMC (P < 0.05). The present
      results implicate miRs in NO and ANP signaling in general and miR-21 in
      particular in cGMP signaling and vascular smooth muscle cell relaxation.

PMID- 21734188
TI  - Human apolipoprotein A-I induces cyclooxygenase-2 expression and prostaglandin I
      2 release in endothelial cells through ATP-binding cassette transporter A1.
AB  - High-density lipoprotein (HDL) can induce cyclooxygenase-2 (COX-2) expression and
      prostacyclin I-2 (PGI-2) release in endothelial cells to exert multiple
      antiatherogenic functions. This effect has been attributed mainly to the role of
      sphingosine-1-phosphate (S1P) integrated in HDL. However, whether apolipoprotein
      A-I (apoA-I), the major apolipoprotein of HDL, could induce COX-2 expression and
      PGI-2 release still remains unclear. In the present study, we selectively
      delipidated HDL and confirmed that apoA-I could facilitate COX-2 expression and
      PGI-2 production in human umbilical vein endothelial cells (HUVECs). ApoA-I, but
      not trypsinized apoA-I, induced COX-2 expression in a time- and dose-dependent
      manner consistent with a key role for apoA-I in this process. Additionally,
      cotreatment of apoA-I with S1P further enhanced COX-2 expression and PGI-2
      production in HUVECs. These effects triggered by apoA-I were not inhibited by
      pertussis toxin, consistent with SIP receptor independent pathway for apoA-I
      effect. Moreover, we demonstrated that the activation of p38 mitogen-activated
      protein kinase (MAPK), extracellular receptor kinase (ERK) 1/2, and JAK2 pathways
      by apoA-I was involved in the expression of COX-2 and the release of PGI-2 in
      HUVECs, and these effects were inhibited by their specific inhibitors,
      respectively. Small interfering RNA experiments showed that ATP binding-cassette
      transporter A1 (ABCA1) was required for COX-2 expression and PGI-2 release
      induced by apoA-I. Thus our results indicate that apoA-I induces COX-2 expression
      and PGI-2 release through ABCA1 and the activation of intracellular p38 MAPK,
      ERK1/2, as well as JAK2 pathways, and apoA-I can reinforce these effects with S1P
      in HUVECs. These novel effects of apoA-I could in part mediate antiatherogenic
      effects of HDL.

PMID- 21734189
TI  - Residues 248-252 and 300-304 of the cardiac Na+/Ca2+ exchanger are involved in
      its regulation by phospholemman.
AB  - Using split cardiac Na(+)/Ca(2+) exchangers (NCX1), we previously demonstrated
      that phospholemman (PLM) regulates NCX1 by interacting with the proximal linker
      domain (residues 218-358) of the intracellular loop of NCX1. With the use of
      overlapping loop deletion mutants, interaction sites are localized to two regions
      spanning residues 238-270 and residues 300-328 of NCX1. In this study, we used
      alanine (Ala) linker scanning to pinpoint the residues in the proximal linker
      domain involved in regulation of NCX1 by PLM. Transfection of human embryonic
      kidney (HEK)293 cells with wild-type (WT) NCX1 or its Ala mutants but not empty
      vector resulted in NCX1 current (I(NaCa)). Coexpression of PLM with WT NCX1
      inhibited I(NaCa). Mutating residues 248-252 (PASKT) or 300-304 (QKHPD) in WT
      NCX1 to Ala resulted in loss of inhibition of I(NaCa) by PLM. By contrast,
      inhibition of I(NaCa) by PLM was preserved when residues 238-242, 243-247, 253
      257, 258-262, 263-267, 305-309, 310-314, 315-319, 320-324, or 325-329 were
      mutated to Ala. While mutating residue 301 to alanine completely abolished PLM
      inhibition, mutation of any single residue 250-252, 300, or 302-304 resulted in
      partial reduction in inhibition. Mutating residues 248-252 to Ala resulted in
      significantly weaker association with PLM. The NCX1-G503P mutant that lacks
      Ca(2+)-dependent activation retained its sensitivity to PLM. We conclude that
      residues 248-252 and 300-304 in the proximal linker domain of NCX1 were involved
      in its inhibition by PLM.

PMID- 21734190
TI  - A simple method for measuring intracellular activities of glutamine synthetase
      and glutaminase in glial cells.
AB  - Here we report and validate a simple method for measuring intracellular
      activities of glial glutamine synthetase (GS) and glutaminase (GLNase) in intact
      glial cells. These enzymes are responsible for glutamate and glutamine recycling
      in the brain, where glutamate and glutamine transport from the blood stream is
      strongly limited by the blood-brain barrier. The intracellular levels of
      glutamate and glutamine are dependent on activities of numerous enzymatic
      processes, including 1) cytosolic production of glutamine from glutamate by GS,
      2) production of glutamate from glutamine by GLNase that is primarily localized
      between mitochondrial membranes, and 3) mitochondrial conversion of glutamate to
      the tricarboxylic cycle intermediate alpha-ketoglutarate in the reactions of
      oxidative deamination and transamination. We measured intracellular activities of
      GS and GLNase by quantifying enzymatic interconversions of L-[(3)H]glutamate and
      L-[(3)H]glutamine in cultured rat astrocytes. The intracellular substrate and the
      products of enzymatic reactions were separated in one step using commercially
      available anion exchange columns and quantified using a scintillation counter.
      The involvement of GS and GLNase in the conversion of (3)H-labeled substrates was
      verified using irreversible pharmacological inhibitors for each of the enzymes
      and additionally validated by measuring intracellular amino acid levels using an
      HPLC. Overall, this paper describes optimized conditions and pharmacological
      controls for measuring GS and GLNase activities in intact glial cells.

PMID- 21734191
TI  - Molecular determinants of PKA-dependent inhibition of TRPC5 channel.
AB  - Canonical transient receptor potential (TRPC) channels are Ca(2+)-permeable,
      nonselective cation channels that are widely expressed in numerous cell types.
      Here, we demonstrate a new mechanism of TPRC isofom 5 (TRPC5) regulation, via
      cAMP signaling via Galpha(s). Monovalent cation currents in human embryonic
      kidney-293 cells transfected with TRPC5 were induced by G protein activation with
      intracellular perfusion of GTPgammaS or by muscarinic stimulation. This current
      could be inhibited by a membrane-permeable analog of cAMP, 8-bromo-cAMP, by
      isoproterenol, by a constitutively active form of Galpha(s) [Galpha(s) (Q227L)],
      and by forskolin. These inhibitory effects were blocked by the protein kinase A
      (PKA) inhibitors, KT-5720 and H-89, as well as by two point mutations at
      consensus PKA phosphorylation sites on TRPC5 (S794A and S796A). Surface
      expression of several mutated versions of TRPC5, quantified using surface
      biotinylation, were not affected by Galpha(s) (Q227L), suggesting that
      trafficking of this channel does not underlie the regulation we report. This
      mechanism of inhibition was also found to be important for the closely related
      channel, TRPC4, in particular for TRPC4alpha, although TRPC4beta was also
      affected. However, this form of regulation was not found to be involved in TRPC6
      and transient receptor potential vanilloid 6 function. In murine intestinal
      smooth muscle cells, muscarinic stimulation-induced cation currents were mediated
      by TRPC4 (>80%) and TRPC6. In murine intestinal smooth muscle cells, 8-bromo
      cAMP, adrenaline, and isoproterenol decreased nonselective cation currents
      activated by muscarinic stimulation or GTPgammaS. Together, these results suggest
      that TRPC5 is directly phosphorylated by G(s)/cAMP/PKA at positions S794 and
      S796. This mechanism may be physiologically important in visceral tissues, where
      muscarinic receptor and beta(2)-adrenergic receptor are involved in the
      relaxation and contraction of smooth muscles.

PMID- 21734192
TI  - Systems analysis of GLP-1 receptor signaling in pancreatic beta-cells.
AB  - Glucagon-like peptide-1 (GLP-1) elevates intracellular concentration of cAMP
      ([cAMP]) and facilitates glucose-dependent insulin secretion in pancreatic beta
      cells. There has been much evidence to suggest that multiple key players such as
      the GLP-1 receptor, G(s) protein, adenylate cyclase (AC), phosphodiesterase
      (PDE), and intracellular Ca(2+) concentration ([Ca(2+)]) are involved in the
      regulation of [cAMP]. However, because of complex interactions among these
      signaling factors, the kinetics of the reaction cascade as well as the activities
      of ACs and PDEs have not been determined in pancreatic beta-cells. We have
      constructed a minimal mathematical model of GLP-1 receptor signal transduction
      based on experimental findings obtained mostly in beta-cells and insulinoma cell
      lines. By fitting this theoretical reaction scheme to key experimental records of
      the GLP-1 response, the parameters determining individual reaction steps were
      estimated. The model reconstructed satisfactorily the dynamic changes in [cAMP]
      and predicted the activities of cAMP effectors, protein kinase A (PKA), and cAMP
      regulated guanine nucleotide exchange factor [cAMP-GEF or exchange protein
      directly activated by cAMP (Epac)] during GLP-1 stimulation. The simulations also
      predicted the presence of two sequential desensitization steps of the GLP1
      receptor that occur with fast and very slow reaction rates. The cross talk
      between glucose- and GLP-1-dependent signal cascades for cAMP synthesis was well
      reconstructed by integrating the direct regulation of AC and PDE by [Ca(2+)]. To
      examine robustness of the signaling system in controlling [cAMP], magnitudes of
      AC and PDE activities were compared in the presence or absence of GLP-1 and/or
      the PDE inhibitor IBMX.(1).

PMID- 21734193
TI  - Wanted: lots of ideas and a sense of what's possible.

PMID- 21734194
TI  - Accountable care organization prototypes: winners and losers?

PMID- 21734195
TI  - What other states can learn from Vermont's bold experiment: embracing a single
      payer health care financing system.
AB  - Single-payer health care systems consist of publicly financed insurance that
      provides basic benefits for all citizens. The design is intended to achieve
      universal coverage and allow greater cost control. Many states have attempted to
      reform their systems around single-payer principles, but none succeeded until
      Vermont enacted a law in May 2011. In this article we describe how our team
      developed a viable single-payer proposal that served as the foundation of
      Vermont's law. According to our estimates, after the first full year of operation
      in 2015, our proposed single-payer system is expected to produce an annual
      savings of 25.3 percent when compared to current state health spending levels;
      cut employer and household health care spending by $200 million; create 3,800
      jobs; and boost the state's overall economic output by $100 million. We describe
      how this plan was designed, and we discuss lessons for other states considering
      health system reform.

PMID- 21734196
TI  - Polling analysis: public support for health reform was broader than reported and
      depended on how proposals were framed.
AB  - The excessive focus of news organizations on "horse race" public opinion polls
      during the debate about health reform in 2010 left the impression that the public
      was fickle, as well as sharply divided on whether the government's role in health
      care should expand. We examined polling data and found that public support for
      health reform depended very much on how individual policies were described. For
      example, support for the public insurance option, which was not included in the
      final version of the Affordable Care Act, ranged from 46.5 percent to 64.6
      percent depending on how pollsters worded their questions. Our findings indicate
      that public support for health reform was broader and more consistent than
      portrayed at the time. Going forward, policy makers should strive to communicate
      how health care policy choices are consistent with existing public preferences or
      should make changes to policy that reflect those preferences.

PMID- 21734197
TI  - Analysis & commentary: The accountable care organization: whatever its growing
      pains, the concept is too vitally important to fail.
AB  - The success of health reform efforts will depend, in part, on creating new and
      better ways to organize, deliver, and pay for health care. Increasingly central
      to this idea is the accountable care organization model proposed for Medicare and
      a slightly different model for commercial health care. But these new health care
      delivery and payment models face considerable skepticism. Can Medicare succeed
      with accountable care organizations if physicians can't determine whether
      patients are in the organization or not? Will commercial hospitals use their
      clout to create accountable care organizations, leaving physician practices in a
      weaker position? This article answers those and other criticisms of the
      developing accountable care organization movement. If the concept fails, the
      nation may face indiscriminate cuts to health care payments, with resulting
      reductions in access, service, and quality.

PMID- 21734198
TI  - Massachusetts e-Health Project increased physicians' ability to use registries,
      and signals progress toward better care.
AB  - The ability to generate and use registries--lists of patients with specific
      conditions, medications, or test results--is considered a measure of physicians'
      engagement with electronic health record systems and a proxy for high-quality
      health care. We conducted a pre-post survey of registry capability among
      physicians participating in the Massachusetts eHealth Collaborative, a four-year,
      $50 million health information technology program. Physicians who participated in
      the program increased their ability to generate some types of registries-
      specifically, for laboratory results and medication use. Our analysis also
      suggested that physicians who used their electronic health records more
      intensively were more likely to use registries, particularly in caring for
      patients with diabetes, compared to physicians reporting less avid use of
      electronic health records. This statewide project may be a viable model for
      regional efforts to expand health information technology and improve the quality
      of care.

PMID- 21734199
TI  - Hospitals respond to Medicare payment shortfalls by both shifting costs and
      cutting them, based on market concentration.
AB  - The coverage expansions planned under the Affordable Care Act are to be financed
      in part by slowing Medicare payment updates to hospitals, thereby reigniting the
      debate over whether low prices paid by public payers cause hospitals to increase
      prices to private insurers--a practice known as cost shifting. Recently, the
      Medicare Payment Advisory Commission (MedPAC) proposed an alternative explanation
      of hospital pricing and profitability that could be used to support policies that
      pressure hospitals to reduce overall costs rather than to only raise prices. This
      study evaluated the cost-shift and MedPAC perspectives using 2008 data on
      hospital margins for 30,514 Medicare and privately insured patients undergoing
      any of seven major procedures in markets where robust hospital competition exists
      and in markets where hospital care is concentrated in the hands of a few
      providers. The study presents empirical evidence that, faced with shortfalls
      between Medicare payments and projected costs, hospitals in concentrated markets
      focus on raising prices to private insurers, while hospitals in competitive
      markets focus on cutting costs. Policy makers need to examine whether efforts to
      promote clinical coordination through provider integration may interfere with
      efforts to restrain overall health care cost growth by restraining Medicare
      payment rates.

PMID- 21734200
TI  - An early look at a four-state initiative to reduce avoidable hospital
      readmissions.
AB  - Launched in 2009, the State Action on Avoidable Rehospitalizations initiative,
      known as STAAR, aims to reduce rates of avoidable rehospitalization in
      Massachusetts, Michigan, Ohio, and Washington by mobilizing state-level
      leadership to improve care transitions. With the program two years into its four
      year cycle, 148 hospitals are working in partnership with more than 500 cross
      continuum team partners. Although there are no publicly available data on whether
      the project is achieving its primary goal of reducing avoidable
      rehospitalizations, the effort has so far been successful in aligning numerous
      complementary initiatives within a state, developing statewide rehospitalization
      data reports, and mobilizing a sizable number of hospitals to work on reducing
      rehospitalizations. More than 90 percent of participating hospitals have formed
      teams to routinely review rehospitalizations with their community-based
      colleagues.

PMID- 21734201
TI  - People & places.
AB  - Improving postdischarge care for patients-regardless of losses in volume or
      revenue.

PMID- 21734202
TI  - Analysis & commentary: A new quality compass: hospital boards' increased role
      under the Affordable Care Act.
AB  - The Affordable Care Act of 2010 promotes a clinically integrated, systems-based
      approach to health care. This means coordinating a patient's care over time and
      across all conditions, diseases, providers, and care settings. The aim is to
      achieve optimal results in terms of the overall quality of care as well as its
      efficiency, cost, safety, and timeliness. Hospital boards, which are legally
      accountable for the quality of the care their institutions provide, need to
      develop and implement effective quality oversight processes to achieve these
      objectives. Boards will have to focus less on the competence of individual
      providers and more on the functioning of the entire system of inpatient and
      outpatient care. We discuss the increased role of the boards in a systems-based
      approach to quality, and what steps they can take to meet the quality mandates of
      the Affordable Care Act.

PMID- 21734203
TI  - Improving health care access for low-income people: lessons from ascension
      health's community collaboratives.
AB  - Communities across the nation are struggling with how to improve access to health
      care for low-income people. We examined seven communities where Ascension Health
      collaborated with other safety-net providers and organizations to achieve better
      health care results for patients. Following a five-step model, each community
      established infrastructure to track the use of services, expand service capacity,
      coordinate care, and encourage the cost-effective use of providers. These efforts
      have achieved notable gains, such as in Austin, Texas, where an estimated $5.50
      was returned for every dollar spent on asthma care. Challenges remain, including
      provider competition, inadequate participation by clinicians, difficulties
      demonstrating impact, and lack of sustainable funding. Lessons gleaned from these
      community collaborations can be valuable as the nation implements health reform,
      and safety-net health care systems home in on remaining access issues.

PMID- 21734204
TI  - Contradicting fears, California's nurse-to-patient mandate did not reduce the
      skill level of the nursing workforce in hospitals.
AB  - When California passed a law in 1999 establishing minimum nurse-to-patient
      staffing ratios for hospitals, it was feared that hospitals might respond by
      disproportionately hiring lower-skill licensed vocational nurses. This article
      examines nurse staffing ratios for California hospitals for the period 1997-2008.
      It compares staffing levels to those in similar hospitals in the United States.
      We found that California's mandate did not reduce the nurse workforce skill level
      as feared. Instead, California hospitals on average followed the trend of
      hospitals nationally by increasing their nursing skill mix, and they primarily
      used more highly skilled registered nurses to meet the staffing mandate. In
      addition, we found that the staffing mandate resulted in roughly an additional
      half-hour of nursing per adjusted patient day beyond what would have been
      expected in the absence of the policy. Policy makers in other states can look to
      California's experience when considering similar approaches to improving patient
      care.

PMID- 21734205
TI  - Mentally ill Medicare patients less likely than others to receive certain types
      of surgery.
AB  - Mentally ill people may face barriers to receiving elective surgical procedures
      as a result of societal stigma and the cognitive, behavioral, and interpersonal
      deficits associated with mental illness. Using data from a cohort of elderly
      Medicare beneficiaries in 2007, we examined whether the mentally ill have less
      access than people without mental illness to several common procedures that are
      typically not for emergencies and are performed at the discretion of the provider
      and the patient. Results suggest that Medicare patients with mental illness are
      30-70 percent less likely than others to receive these "referral-sensitive"
      surgical procedures. Those who did undergo an elective procedure generally
      experienced poorer outcomes both in the hospital and after discharge. Efforts to
      improve access to and outcomes of nonpsychiatric care for mentally ill patients
      are warranted.

PMID- 21734206
TI  - Differences in the volume of services and in prices drive big variations in
      Medicaid spending among US states and regions.
AB  - It is well known that Medicaid spending per beneficiary varies widely across
      states. However, less is known about the cause of this variation, or about
      whether increased spending is associated with better outcomes. In this article we
      describe and analyze sources of interstate variation in Medicaid spending over
      several years. We find substantial variations both in the volume of services and
      in prices. Overall, per capita spending in the ten highest-spending states was
      $1,650 above the average national per capita spending, of which $1,186, or 72
      percent, was due to the volume of services delivered. Spending in the ten lowest
      spending states was $1,161 below the national average, of which $672, or 58
      percent, was due to volume. In the mid-Atlantic region, increased price and
      volume resulted in the most expensive care among regions, whereas reduced price
      and volume in the South Central region resulted in the least expensive care among
      regions. Understanding these variations in greater detail should help improve the
      quality and efficiency of care-a task that will become more important as Medicaid
      is greatly expanded under the Affordable Care Act of 2010.

PMID- 21734207
TI  - Reinventing Medicaid: state innovations to qualify and pay for patient-centered
      medical homes show promising results.
AB  - This article describes patient-centered medical home initiatives that seventeen
      states have launched. These initiatives use national recognition or state-based
      qualification standards along with incentive payments to address soaring costs
      and lagging health outcomes in state Medicaid programs. Even though these
      initiatives are in their infancy, early results are encouraging. Modest increases
      in payment to physicians, aligned with quality improvement standards, have not
      only resulted in promising trends for costs and quality, but have also greatly
      improved access to care. Several state programs have already demonstrated
      declines in per capita costs for patients enrolled in Medicaid; increased
      participation of physicians in caring for Medicaid patients; and high patient and
      provider satisfaction. These early results give states good reason to continue
      developing patient-centered medical homes as part of their Medicaid programs.
      This article provides a closer look at these innovative models, to inform public
      and private reform efforts.

PMID- 21734208
TI  - Medicaid patients seen at federally qualified health centers use hospital
      services less than those seen by private providers.
AB  - Federally qualified health centers, also known as community health centers, play
      an essential role in providing health care to millions of Americans. In return
      for providing primary care to underserved, homeless, and migrant populations,
      these centers are reimbursed at a higher rate than other providers by public
      programs such as Medicaid. Under the Affordable Care Act of 2010, the role of the
      centers is expected to grow. To examine the quality of care that the centers
      provide, the Colorado Department of Health Care Policy and Financing compared the
      use of costly hospital-related services by Medicaid clients whose usual source of
      care was a community health center with the use by clients whose usual source of
      care was a private, fee-for-service provider. The study found that community
      health center users were about one-third less likely than the other group to have
      emergency department visits, inpatient hospitalizations, or preventable hospital
      admissions. Public funders such as states should work with community health
      centers to improve the quality and reduce the cost of care even further.

PMID- 21734209
TI  - Dropped medical malpractice claims: their surprising frequency, apparent causes,
      and potential remedies.
AB  - Most medical malpractice claims are neither settled nor adjudicated. Instead,
      they are abandoned by the plaintiffs who bring them. This study measured the
      frequency and cost of abandoned claims and gathered opinions from attorneys and
      other experts on why plaintiffs drop claims. Plaintiffs in the study abandoned
      58.6 percent of claims against defendants, while settling only 26.6 percent and
      adjudicating 14.8 percent. Claims are not dropped because a large percentage of
      them are frivolous, but for other reasons. The most important is that as
      plaintiffs acquire more information in the course of a lawsuit, they often
      conclude that a claim is weaker than they had first thought. The author
      recommends that insurers and hospitals adopt new procedures to encourage both
      plaintiff attorneys and defense representatives to exchange information more
      efficiently, discuss the merits of malpractice cases more candidly, and resolve
      cases quickly. Such reforms would greatly reduce both the frequency and the
      duration of cases that are dropped, and thus the cost of malpractice litigation.

PMID- 21734210
TI  - The use of generic drugs in prevention of chronic disease is far more cost
      effective than thought, and may save money.
AB  - In this article we highlight the important role that medication therapy can play
      in preventing disease and controlling costs. Focusing on coronary artery disease,
      we demonstrate that prevention, with the appropriate use of generic medications,
      appears far more cost-effective than previously documented, and it may even save
      on costs. For example, an earlier study estimated that reducing blood pressure to
      widely established clinical guidelines in nondiabetic patients cost an estimated
      $52,983 per quality-adjusted life-year if a brand-name drug was used. However, we
      estimate that the cost is just $7,753 per quality-adjusted life-year at generic
      medication prices. As the nation attempts to find strategies to improve
      population health without adding to the unsustainably high cost of care, policy
      makers should focus on ensuring that patients have access to essential generic
      medications.

PMID- 21734211
TI  - The Care Span: Growth of racial and ethnic minorities in US nursing homes driven
      by demographics and possible disparities in options.
AB  - Between 1999 and 2008, the number of elderly Hispanics and Asians living in US
      nursing homes grew by 54.9 percent and 54.1 percent, respectively, while the
      number of elderly black residents increased 10.8 percent. During the same period,
      the number of white nursing home residents declined 10.2 percent. These shifts
      have been driven in part by changing demographics, especially the fast growth of
      older minority populations. However, the numbers of minority residents in nursing
      homes increased more rapidly than the minority population overall, even in areas
      with high concentrations of minority populations. Thus, these results may
      indicate unequal minority access to home and community-based alternatives, which
      are generally preferred for long-term care. When designing initiatives to balance
      institutional and noninstitutional long-term care, policy makers should take
      steps to reduce racial and ethnic disparities.

PMID- 21734213
TI  - Narrative matters. 'Oh, my father hit me'.

PMID- 21734212
TI  - The Care Span: Medicaid savings resulted when community health workers matched
      those with needs to home and community care.
AB  - The Affordable Care Act of 2010 builds on earlier efforts to expand home and
      community-based alternatives to institutional long-term care. Identifying people
      living in the community who have unmet long-term care needs and who may be at
      risk for entering nursing homes may be crucial to these efforts. The Arkansas
      Community Connector Program used specially trained community health workers to
      identify such people in three disadvantaged counties and connect them to Medicaid
      home and community-based services. The result was a 23.8 percent average
      reduction in annual Medicaid spending per participant during the period 2005-08.
      Net three-year savings to the Arkansas Medicaid program equaled $2.619 million.
      Similar interventions may help other localities achieve cost-saving and equitable
      access to publicly funded long-term care options other than institutional care.

PMID- 21734214
TI  - GrantWatch outcomes.

PMID- 21734215
TI  - Missing data on air pollution.

PMID- 21734216
TI  - Quality improvement programs for patient care.

PMID- 21734218
TI  - Involving front-line clinicians in reducing medical errors.

PMID- 21734219
TI  - Speaking up to prevent medical errors.

PMID- 21734220
TI  - Global asymptotic stability for HIV-1 dynamics with two distributed delays.
AB  - Based on the drugs treatment to control HIV-1 infection and viral replication, we
      express the intracellular eclipse phase of virions in host cell as distributed
      delays because of pharmacological actions. In present paper, we investigate a
      class of HIV-1 infection dynamical model with two distributed delays. One of them
      describes the period between the time that HIV virion enters (infects) target
      cell and the time that the infected cell starts to produce new viral particles.
      The other describes the time for the virion maturation process. They are both
      allowed to tend to be infinite because of drugs resistent strains. By the
      Lyapunov direct method of and utilizing the technology of constructing Lyapunov
      functionals, we identify the basic reproduction number R(0) as a threshold
      quantity for the stability of equilibria. More precisely, if R(0) <= 1, the
      infection-free equilibrium is globally asymptotically stable; on the contrary, if
      R(0) > 1, then an infected equilibrium appears which is globally asymptotically
      stable. The dynamical results indicate that time delays have effect on the global
      stability of two equilibria through threshold value R(0), which is a decreasing
      function of delays. The biological meanings imply that any drugs that can prolong
      the time of viral reproduction through slowing down the reverse transcription of
      HIV in host and virus maturation process may also help control the HIV-1
      infection and virus loads. Another way to increase the efficacy of the protease
      inhibitor and the reverse transcriptase inhibitor (i.e. increasing n(p) and
      n(rt)) is also desirable treatment strategies.

PMID- 21734221
TI  - Trabectedin plus pegylated liposomal doxorubicin in the treatment of patients
      with partially platinum-sensitive ovarian cancer: current evidence and future
      perspectives.
AB  - The effectiveness of platinum re-treatment in relapsed ovarian cancer depends on
      relapse-free/treatment-free intervals. Platinum agents can be effectively
      readministered to platinum-sensitive patients (relapsing >12 months after
      platinum), but efficacy is lower in partially platinum-sensitive (PPS) disease
      (relapsing 6-12 months after platinum). There is no clear standard treatment
      challenging PPS patients. Survival data in this subset with chemotherapy
      combinations such as pegylated liposomal doxorubicin (PLD) plus carboplatin or
      gemcitabine plus PLD are available from phase II trials ranging from 16 to 21
      months. Recent results from OVA-301 phase III randomized trial evaluating
      trabectedin plus PLD showed the longest median overall survival ever reported in
      PPS patients (23 months). Subsequent chemotherapy (including platinum-based
      regimens) was administered later and survival in patients receiving third-line
      platinum was longer in patients treated with trabectedin plus PLD compared with
      those treated with PLD alone. These results suggest that prolonging platinum-free
      interval (PFI) with an effective non-platinum regimen improves outcome with
      subsequent third-line platinum treatment. An ongoing phase III trial (INOVATYON)
      aims to demonstrate if the results observed with trabectedin plus PLD in PPS
      patients are due to PFI extension, and if PFI extension with non-platinum
      combination prolongs response to subsequent platinum and survival in this
      population.

PMID- 21734222
TI  - Re: Patterson, P., Millar, B., & Visser, A. (2011). The development of an
      instrument to assess the unmet needs of young people who have a sibling with
      cancer: piloting the Sibling Cancer needs Instrument (SCNI). Journal of Pediatric
      Oncology Nursing, 28(1), 6-15.

PMID- 21734223
TI  - Nursing the patient with developmental disability in hospital: roles of paid
      carers.
AB  - Our aim in this narrative inquiry was to understand the roles of paid carers
      supporting adults with developmental disability and complex communication needs
      in hospital, from the perspectives of 15 paid carers, 15 adults with
      developmental disability, and 15 hospital nurses. Results demonstrated that paid
      carers have an important role in supporting the adult with disability, providing
      information, delivering basic care, and facilitating communication. Stories
      reflected paid carer volunteerism; lack of orientation of carers and hospital
      staff to the paid carers' roles; blurred role boundaries between paid carers,
      family carers, and nurses; and paid carers being uncertain about their own
      responsibilities for staff and patient safety. New policies and practice
      guidelines are needed to guide both health and disability services in clarifying
      paid carer roles and role boundaries, and to enable paid carers and hospital
      staff to work together effectively on the ward in the care of adults with
      developmental disability.

PMID- 21734224
TI  - Cancer patients' preferences for control at the end of life.
AB  - The achievement of a death consistent with personal preferences is an elusive
      outcome for most people with cancer. Maintaining a sense of control is a core
      component of a dignified death; however, control might be a Western bioethical
      notion with questionable relevance to culturally diverse groups. Thus, the
      purpose of our study was to explore the meaning of control and control
      preferences in a group of racially and ethnically diverse patients with an
      advanced cancer diagnosis. Using a hermeneutic, phenomenological approach, we
      interviewed 20 patients with advanced cancer and uncovered two themes: (a)
      preferences for everyday control over treatment decisions, family issues, final
      days of life, and arrangements after death, vs. (b) awareness that cancer and
      death are controlled by a higher power. Although the sample included non-Hispanic
      Whites, African Americans, and Hispanics, participants shared common views that
      are characteristic of American cultural norms regarding the value of autonomy.

PMID- 21734225
TI  - Interviews on end-of-life care with older people: reflections on six european
      studies.
AB  - Qualitative research provides important insights into the experiences and
      perspectives of older people on end-of-life issues, but such research is
      methodologically and ethically complex. We offer a set of reflections from six
      end-of-life care studies conducted with older people in four European countries:
      Belgium, Germany, the Netherlands, and the United Kingdom. The reflection process
      was informed by four full-day meetings between the authors and referral to
      sources including the study interview guides, summary "pen portraits" about key
      issues encountered in the interviews, and key sections of the interview
      transcripts. We identified as major challenges accessing people, the introduction
      of end-of-life issues in an interview, managing emotions, the presence of
      companions, and reciprocity. Formal ethical review committees rarely take into
      account these complex issues. We concluded that is it necessary to maintain an
      ongoing reflexive stance to enhance qualitative research practice in the
      intersecting fields of aging and end-of-life studies.

PMID- 21734226
TI  - Understanding exercise uptake and adherence for people with chronic conditions: a
      new model demonstrating the importance of exercise identity, benefits of
      attending and support.
AB  - Understanding the factors influencing uptake and adherence to exercise for people
      with chronic conditions from different ages, genders and ethnicities is important
      for planning exercise services. This paper presents evidence supporting a new
      model of exercise uptake and adherence applicable to people with chronic
      conditions from diverse socio-demographic backgrounds. The study is based on 130
      semi-structured interviews with people with chronic conditions, including both
      those who did and those who did not attend exercise services, and supporters of
      those who attended. Analysis followed the guidelines of 'framework analysis'.
      Results show that three factors were particularly important in influencing
      adherence behavior: (i) exercise identity, (ii) support and (iii) perceived
      benefits of attending. Social and cultural identities impacted on willingness to
      exercise, importance of exercise and perceived appropriateness of exercising.
      Having at least one supporter providing different types of support was associated
      with high levels of attendance. Those people who valued the social and
      psychological benefits of attending were more likely to be high attenders. The
      new model illustrates interaction between these three factors and discusses how
      these can be taken into account when planning exercise services for people with
      chronic conditions drawn from diverse socio-demographic groups.

PMID- 21734227
TI  - Longitudinal assessment of hematopoietic stem cell transplantation and
      hyposalivation.
AB  - Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and
      neck cancer, causing impaired quality of life and predisposition to oral
      infections. However, data on the effects of hematopoietic stem cell
      transplantation (HSCT) on salivary secretion are scarce. The present study
      determined stimulated whole-saliva flow rates in HSCT recipients in comparison
      with a healthy control group. Stimulated whole-saliva flow rates of 228
      allogeneic HSCT recipients (134 males, 94 females; mean age, 43 yrs) were
      examined pre-HSCT and 6, 12, and 24 months post-HSCT. Healthy individuals (n =
      144; 69 males, 75 females; mean age, 46 yrs) served as the control group.
      Stimulated saliva flow rates (mL/min) were measured and analyzed statistically,
      stratifying for hematological diagnoses and conditioning therapy. Hyposalivation
      (<= 0.7 mL/min) was found in 40% (p < 0.00001), 53% (p < 0.00001), 31% (p <
      0.01), and 26% (n.s.) of the recipients pre-HSCT, and 6, 12, and 24 months post
      HSCT, respectively, whereas 16% of the control individuals had hyposalivation.
      Severe hyposalivation (<= 0.3 mL/min) was found in 11%, 18%, 4%, and 4% of the
      recipients pre-HSCT, and 6, 12, and 24 months post-HSCT, respectively.
      Additionally, conditioning regimen and sex had an impact on saliva flow. In
      conclusion, hyposalivation was observed to be a common but generally reversible
      complication among HSCT recipients.

PMID- 21734228
TI  - Improving DHH students' grammar through an individualized software program.
AB  - The purpose of this study was to determine if the frequent use of a targeted,
      computer software grammar instruction program, used as an individualized
      classroom activity, would influence the comprehension of morphosyntax structures
      (determiners, tense, and complementizers) in deaf/hard-of-hearing (DHH)
      participants who use American Sign Language (ASL). Twenty-six students from an
      urban day school for the deaf participated in this study. Two hierarchical linear
      modeling growth curve analyses showed that the influence of LanguageLinks: Syntax
      Assessment and Intervention (LL) resulted in statistically significant gains in
      participants' comprehension of morphosyntax structures. Two dependent t tests
      revealed statistically significant results between the pre- and postintervention
      assessments on the Diagnostic Evaluation of Language Variation-Norm Referenced.
      The daily use of LL increased the morphosyntax comprehension of the participants
      in this study and may be a promising practice for DHH students who use ASL.

PMID- 21734229
TI  - Effects of daily stressors on the psychological and biological well-being of
      spouses of persons with mild cognitive impairment.
AB  - OBJECTIVES: This research documents spousal accounts of daily symptoms and
      behaviors of their husbands or wives with mild cognitive impairment (MCI) and
      assesses how MCI-related symptoms and care needs are associated with spouse care
      partners' psychological well-being and biomarkers of physiological wear and tear.
      METHOD: Thirty spouse care partners participated in a 7-day diary study and
      reported on behavior problems associated with MCI as well as daily stressors and
      strains they experienced. They also provided saliva samples on 4 of the study
      days. RESULTS: Multilevel models revealed daily variability and change in
      psychological affect and the diurnal cortisol rhythm. Daily primary stressors,
      everyday secondary strains, and marital interactions predicted these changes.
      DISCUSSION: The findings document the negative physiological effects of having a
      spouse with MCI and provide new details on probable causes of psychological and
      biological distress. They shed light on MCI-specific interventions to address
      couples' needs before severe disease progression occurs that could interfere with
      spouses' ability to provide home-based care and support.

PMID- 21734230
TI  - The Cox-2 -1195 G > A polymorphism and cancer risk: a meta-analysis of 25 case
      control studies.
AB  - Cyclooxygenase 2 (Cox-2, a rate-limiting enzyme in the conversion of arachidonic
      acid to prostanoids) has been implicated in several physiological and
      pathological processes, and it has been reported that polymorphisms in the
      regulatory region of Cox-2 might influence its expression, contributing to the
      interindividual susceptibility to cancer. However, results from published studies
      on the association between the Cox-2 -1195G > A polymorphism and the risk of
      cancer are conflicting. We performed a meta-analysis based on 25 case-control
      studies, including a total of 9482 cancer cases and 12 206 controls to derive a
      more precise estimation of the association and its possible influence on cancer
      risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the
      strength of the association. The overall results indicated that the variant
      genotypes moderately increased risk of cancer (AA/AG versus GG, OR = 1.15, 95%
      CI: 1.02-1.31). In the stratified analysis for the -1195G > A polymorphism, a
      proximate association was observed in Asian populations (AA/AG versus GG, OR =
      1.28, 95% CI: 1.12-1.46), but no significant association except for oesophageal
      cancer and 'others' was found when stratified by cancer type. In conclusion, our
      meta-analysis indicates that -1195G > A of Cox-2 is a low penetration risk factor
      for cancer.

PMID- 21734231
TI  - Validation of an armband to measure daily energy expenditure in older adults.
AB  - BACKGROUND: Objective methods to measure daily energy expenditure in studies of
      aging are needed. We sought to determine the accuracy of total energy expenditure
      (TEE) and activity energy expenditure (AEE) estimates from the SenseWear Pro
      armband (SWA) using software versions 6.1 (SWA 6.1) and 5.1 (SWA 5.1) relative to
      criterion methods in free-living older adults. METHODS: Participants (n = 19,
      mean age 82.0 years) wore a SWA for a mean +/- SD 12.5 +/- 1.1 days, including
      while sleeping. During this same period, criterion values for TEE were assessed
      with doubly labeled water and for resting metabolic rate (RMR) with indirect
      calorimetry. AEE was calculated as 0.9 TEE - RMR. RESULTS: For TEE, there was no
      difference in mean +/- SD values from doubly labeled water (2,040 +/- 472
      kcal/day) versus SWA 6.1 (2,012 +/- 497 kcal/day, p = .593) or SWA 5.1 (2,066 +/-
      474 kcal/day, p = .606); individual values were highly correlated between methods
      (SWA 6.1 r = .893, p < .001; SWA 5.1 r = .901, p < .001) and demonstrated strong
      agreement (SWA 6.1 intraclass correlation coefficient = .896; SWA 5.1 intraclass
      correlation coefficient = .904). For AEE, mean values from SWA 6.1 (427 +/- 304
      kcal/day) were lower by 26.8% than criterion values (583 +/- 242 kcal/day, p =
      .003), and mean values from SWA 5.1 (475 +/- 299 kcal/day) were lower by 18.5%
      than criterion values (p = .021); however, individual values were highly
      correlated between methods (SWA 6.1 r = .760, p < .001; SWA 5.1 r = .786, p <
      .001) and demonstrated moderate agreement (SWA 6.1 intraclass correlation
      coefficient = .645; SWA 5.1 intraclass correlation coefficient = .720). Bland
      Altman plots identified no systematic bias for TEE or AEE. CONCLUSIONS:
      Acceptable levels of agreement were observed between SWA and criterion
      measurements of TEE and AEE in older adults.

PMID- 21734232
TI  - The vitronectin-binding function of PAI-1 exacerbates lung fibrosis in mice.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is increased in the lungs of patients
      with pulmonary fibrosis, and animal studies have shown that experimental
      manipulations of PAI-1 levels directly influence the extent of scarring that
      follows lung injury. PAI-1 has 2 known properties that could potentiate fibrosis,
      namely an antiprotease activity that inhibits the generation of plasmin, and a
      vitronectin-binding function that interferes with cell adhesion to this
      extracellular matrix protein. To determine the relative importance of each PAI-1
      function in lung fibrogenesis, we administered mutant PAI-1 proteins that
      possessed either intact antiprotease or vitronectin-binding activity to bleomycin
      injured mice genetically deficient in PAI-1. We found that the vitronectin
      binding capacity of PAI-1 was the primary determinant required for its ability to
      exacerbate lung scarring induced by intratracheal bleomycin administration. The
      critical role of the vitronectin-binding function of PAI-1 in fibrosis was
      confirmed in the bleomycin model using mice genetically modified to express the
      mutant PAI-1 proteins. We conclude that the vitronectin-binding function of PAI-1
      is necessary and sufficient in its ability to exacerbate fibrotic processes in
      the lung.

PMID- 21734234
TI  - Next-generation leukemia immunotherapy.
AB  - Allogeneic hematopoietic cell transplantation led to the discovery of the
      allogeneic GVL effect, which remains the most convincing evidence that immune
      cells can cure cancer in humans. However, despite its great paradigmatic and
      clinical relevance, induction of GVL by conventional allogeneic hematopoietic
      cell transplantation remains a quite rudimentary form of leukemia immunotherapy.
      It is toxic and its efficacy is far from optimal. It is therefore sobering that
      since the discovery of the GVL effect 3 decades ago, the way GVL is induced and
      manipulated has practically not changed. Preclinical and clinical studies suggest
      that injection of T cells primed against a single Ag present on neoplastic cells
      could enhance the GVL effect without causing any GVHD. We therefore contend that
      Ag-targeted adoptive T-cell immunotherapy represents the future of leukemia
      immunotherapy, and we discuss the specific strategies that ought to be evaluated
      to reach this goal. Differences between these strategies hinge on 2 key elements:
      the nature of the target Ag and the type of Ag receptor expressed on T cells.

PMID- 21734233
TI  - Inhibition of TET2-mediated conversion of 5-methylcytosine to 5
      hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of
      human hematopoietic progenitors.
AB  - TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is
      frequently mutated in myeloid malignancies, including myeloproliferative
      neoplasms. Here we show that the level of 5-hmC is decreased in granulocyte DNA
      from myeloproliferative neoplasm patients with TET2 mutations compared with
      granulocyte DNA from healthy patients. Inhibition of TET2 by RNA interference
      decreases 5-hmC levels in both human leukemia cell lines and cord blood CD34(+)
      cells. These results confirm the enzymatic function of TET2 in human
      hematopoietic cells. Knockdown of TET2 in cord blood CD34(+) cells skews
      progenitor differentiation toward the granulomonocytic lineage at the expense of
      lymphoid and erythroid lineages. In addition, by monitoring in vitro
      granulomonocytic development we found a decreased granulocytic differentiation
      and an increase in monocytic cells. Our results indicate that TET2 disruption
      affects 5-hmC levels in human myeloid cells and participates in the pathogenesis
      of myeloid malignancies through the disturbance of myeloid differentiation.

PMID- 21734235
TI  - Applicability of a "Pick a Winner" trial design to acute myeloid leukemia.
AB  - Randomized clinical trials remain the gold standard to establish efficacy and
      safety of new treatments. In acute myeloid leukemia, large trials have been
      associated with gradual improvement in outcome over 2 decades in younger patients
      without major differences emerging between treatments. By contrast, in older
      patients, improvement has been minimal, which justifies a new approach to
      identifying effective treatments. Given the urgent unmet need, and with the
      emergence of several novel agents or combinations that are likely to be
      expensive, large benefits are probably required to change clinical practice. To
      address this issue, we have evolved a "Pick a Winner" randomized progressive
      design with a rolling incorporation of novel treatments (drug X), which has been
      tested in older patients with acute myeloid leukemia. The rationale, operational
      characteristics, and initial experience of such an approach in the context of the
      United Kingdom National Cancer Research Institute AML16 trial are presented.

PMID- 21734236
TI  - A human promyelocytic-like population is responsible for the immune suppression
      mediated by myeloid-derived suppressor cells.
AB  - We recently demonstrated that human BM cells can be treated in vitro with defined
      growth factors to induce the rapid generation of myeloid-derived suppressor cells
      (MDSCs), hereafter defined as BM-MDSCs. Indeed, combination of G-CSF + GM-CSF led
      to the development of a heterogeneous mixture of immature myeloid cells ranging
      from myeloblasts to band cells that were able to suppress alloantigen- and
      mitogen-stimulated T lymphocytes. Here, we further investigate the mechanism of
      suppression and define the cell subset that is fully responsible for BM-MDSC
      mediated immune suppression. This population, which displays the structure and
      markers of promyelocytes, is however distinct from physiologic promyelocytes
      that, instead, are devoid of immuosuppressive function. In addition, we
      demonstrate that promyelocyte-like cells proliferate in the presence of activated
      lymphocytes and that, when these cells exert suppressive activity, they do not
      differentiate but rather maintain their immature phenotype. Finally, we show that
      promyelocyte-like BM-MDSCs are equivalent to MDSCs present in the blood of
      patients with breast cancer and patients with colorectal cancer and that
      increased circulating levels of these immunosuppressive myeloid cells correlate
      with worse prognosis and radiographic progression.

PMID- 21734237
TI  - Escape from highly effective public CD8+ T-cell clonotypes by HIV.
AB  - Mapping the precise determinants of T-cell efficacy against viruses in humans is
      a public health priority with crucial implications for vaccine design. To inform
      this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell
      clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10
      epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known
      to confer superior control of viral replication in HIV-infected individuals.
      Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1
      3 gene rearrangements, were found to be preferentially selected in vivo and
      shared between individuals. These "public" clonotypes exhibit high levels of TCR
      avidity and Ag sensitivity, which impart functional advantages and enable
      effective suppression of HIV replication. The early L(268)M mutation at position
      6 of the KK10 epitope enables the virus to avoid recognition by these highly
      effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant
      reactivity provide flexibility within the overall KK10-specific response. These
      findings provide refined mechanistic insights into the workings of an effective
      CD8(+) T-cell response against HIV.

PMID- 21734238
TI  - Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with
      increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells.
AB  - Previous work has demonstrated that both rapamycin (RAPA) and IL-2 enhance
      CD4+CD25+Foxp3+ regulatory T-cell (Treg) proliferation and function in vitro. We
      investigated whether the combination of RAPA plus IL-2 could impact acute GVHD
      induction after bone marrow transplantation (BMT). RAPA plus IL-2 resulted in
      improved survival and a reduction in acute GVHD lethality associated with an
      increased expansion of donor type CD4+Foxp3+ Tregs and reduced CD4+CD25-
      conventional T cells (Tcons). RAPA plus IL-2, but not either drug alone,
      increased both expansion of donor natural Tregs and conversion of induced Tregs
      from donor CD25- Tcons while IL-2 alone increased conversion of Tregs from CD25-
      Tcon. RAPA plus IL-2 treatment resulted in less production of IFN-gamma and TNF,
      cytokines known to be important in the initiation of acute GVHD. These studies
      indicate that the pharmacologic stimulation of T cells with IL-2 and the
      suppression of Tcon proliferation with RAPA result in a selective expansion of
      functional Tregs and suppression of acute GVHD.

PMID- 21734239
TI  - The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS
      production, and targets leukemia cells in AML.
AB  - Recent studies have shown that 3-Deazaneplanocin A (DZNep), a histone
      methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and
      preferentially induces apoptosis in cancer cells, including acute myeloid
      leukemia (AML). However, the underlying molecular mechanisms are not well
      understood. The present study demonstrates that DZNep induces robust apoptosis in
      AML cell lines, primary cells, and targets CD34(+)CD38(-) leukemia stem cell
      (LSC)-enriched subpopulations. Using RNA interference (RNAi), gene expression
      profiling, and ChIP, we identified that TXNIP, a major redox control molecule,
      plays a crucial role in DZNep-induced apoptosis. We show that disruption of PRC2,
      either by DZNep treatment or EZH2 knockdown, reactivates TXNIP, inhibits
      thioredoxin activity, and increases reactive oxygen species (ROS), leading to
      apoptosis. Furthermore, we show that TXNIP is down-regulated in AML and is a
      direct target of PRC2-mediated gene silencing. Consistent with the ROS
      accumulation on DZNep treatment, we also see a signature of endoplasmic reticulum
      (ER) stress-regulated genes, commonly associated with cell survival, down
      regulated by DZNep. Taken together, we uncover a novel molecular mechanism of
      DZNep-mediated apoptosis and propose that EZH2 may be a potential new target for
      epigenetic treatment in AML.

PMID- 21734240
TI  - Accumulation of oxidative DNA damage restricts the self-renewal capacity of human
      hematopoietic stem cells.
AB  - Stem cells of highly regenerative organs including blood are susceptible to
      endogenous DNA damage caused by both intrinsic and extrinsic stress. Response
      mechanisms to such stress equipped in hematopoietic stem cells (HSCs) are crucial
      in sustaining hematopoietic homeostasis but remain largely unknown. In this
      study, we demonstrate that serial transplantation of human HSCs into
      immunodeficient mice triggers replication stress that induces incremental
      elevation of intracellular reactive oxygen species (ROS) levels and the
      accumulation of persistent DNA damage within the human HSCs. This accumulation of
      DNA damage is also detected in HSCs of clinical HSC transplant patients and
      elderly individuals. A forced increase of intracellular levels of ROS by
      treatment with a glutathione synthetase inhibitor aggravates the extent of DNA
      damage, resulting in the functional impairment of HSCs in vivo. The oxidative DNA
      damage activates the expression of cell-cycle inhibitors in a HSC specific
      manner, leading to the premature senescence among HSCs, and ultimately to the
      loss of stem cell function. Importantly, treatment with an antioxidant can
      antagonize the oxidative DNA damage and eventual HSC dysfunction. The study
      reveals that ROS play a causative role for DNA damage and the regulation of ROS
      have a major influence on human HSC aging.

PMID- 21734241
TI  - Antiphospholipid antibodies induce translocation of TLR7 and TLR8 to the endosome
      in human monocytes and plasmacytoid dendritic cells.
AB  - The antiphospholipid syndrome (APS) is an autoimmune disease characterized by
      thromboembolic events and/or fetal loss in the presence of antiphospholipid
      antibodies (aPLs). The mechanisms underlying the pathogenicity of aPLs are still
      poorly understood. Here we show that 3 human monoclonal aPLs as well as IgG
      fractions from patients with the APS increase mRNA expression of the
      intracellular toll-like receptor (TLR) 7 in plasmacytoid dendritic cells and TLR8
      in monocytes. Simultaneously they induce the translocation of TLR7 or TLR8 from
      the endoplasmic reticulum to the endosome. These effects depend on the uptake of
      aPLs into the endosome, subsequent activation of endosomal NADPH oxidase, and
      generation of superoxide. As a consequence cells are dramatically sensitized to
      ligands for TLR7 and TLR8. This observation delineates a novel signal
      transduction pathway in innate immunity originating from the endosome. Because
      the overexpression of TLR7 can also be detected in plasmacytoid dendritic cells
      from patients with the APS ex vivo, our results provide an explanation for
      proinflammatory and procoagulant effects of aPLs. Because inappropriate
      expression of TLR7 has been implicated in the development of systemic
      autoimmunity, these findings may also be relevant for the understanding of
      autoimmunity.

PMID- 21734242
TI  - Review and international recommendation of methods for typing neisseria
      gonorrhoeae isolates and their implications for improved knowledge of gonococcal
      epidemiology, treatment, and biology.
AB  - Gonorrhea, which may become untreatable due to multiple resistance to available
      antibiotics, remains a public health problem worldwide. Precise methods for
      typing Neisseria gonorrhoeae, together with epidemiological information, are
      crucial for an enhanced understanding regarding issues involving epidemiology,
      test of cure and contact tracing, identifying core groups and risk behaviors, and
      recommending effective antimicrobial treatment, control, and preventive measures.
      This review evaluates methods for typing N. gonorrhoeae isolates and recommends
      various methods for different situations. Phenotypic typing methods, as well as
      some now-outdated DNA-based methods, have limited usefulness in differentiating
      between strains of N. gonorrhoeae. Genotypic methods based on DNA sequencing are
      preferred, and the selection of the appropriate genotypic method should be guided
      by its performance characteristics and whether short-term epidemiology
      (microepidemiology) or long-term and/or global epidemiology (macroepidemiology)
      matters are being investigated. Currently, for microepidemiological questions,
      the best methods for fast, objective, portable, highly discriminatory,
      reproducible, typeable, and high-throughput characterization are N. gonorrhoeae
      multiantigen sequence typing (NG-MAST) or full- or extended-length porB gene
      sequencing. However, pulsed-field gel electrophoresis (PFGE) and Opa typing can
      be valuable in specific situations, i.e., extreme microepidemiology, despite
      their limitations. For macroepidemiological studies and phylogenetic studies, DNA
      sequencing of chromosomal housekeeping genes, such as multilocus sequence typing
      (MLST), provides a more nuanced understanding.

PMID- 21734243
TI  - Onchocerciasis: the role of Wolbachia bacterial endosymbionts in parasite
      biology, disease pathogenesis, and treatment.
AB  - The discovery of Wolbachia intracellular bacteria within filarial nematodes,
      including Onchocerca volvulus, the causative agent of onchocerciasis or "river
      blindness," has delivered a paradigm shift in our understanding of the parasite's
      biology, to where we now know that the bacterial endosymbionts are essential for
      normal development of larvae and embryos and may support the long-term survival
      of adult worms. The apparent mutualistic dependency has also offered a novel
      approach to the treatment of onchocerciasis through the use of antibiotics to
      eliminate Wolbachia, delivering for the first time a treatment which has
      significant macrofilaricidal efficacy. Studies with other filarial nematode
      species have also highlighted a role for Wolbachia in transmission and infection
      of the mammalian host through a fascinating manipulation of mast cell-mediated
      vasodilation to enhance infectivity of vector-borne larvae. Wolbachia has also
      been identified as the principal driver of innate and adaptive Th1 inflammatory
      immunity, which can either contribute to disease pathogenesis or, with the
      Wolbachia-mediated recruitment of mast cells, enhance infectivity. The Wolbachia
      activation of innate inflammation also drives inflammatory adverse events in
      response to chemotherapy with either diethylcarbamazine (DEC) or ivermectin. In
      this review we summarize the experimental and field trial data which have
      uncovered the importance of Wolbachia symbiosis in onchocerciasis.

PMID- 21734245
TI  - Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkappaBalpha
      deficiency.
AB  - Autosomal recessive IRAK-4 and MyD88 deficiencies predispose affected patients to
      recurrent invasive pyogenic bacterial infection. Both defects result in the
      selective impairment of cellular responses to Toll-like receptors (TLRs) other
      than TLR3 and of cellular responses to most interleukin-1 receptors (IL-1Rs),
      including IL-1R, IL-18R, and IL-33R. Hypomorphic mutations in the X-linked NEMO
      gene and hypermorphic mutations in the autosomal IKBA gene cause X-linked
      recessive and autosomal dominant anhidrotic ectodermal dysplasia with
      immunodeficiency (EDA-ID) syndromes. Both of these defects impair NF-kappaB
      mediated cellular responses to multiple receptors, including TLRs, IL-1Rs, and
      tumor necrosis factor receptors (TNF-Rs). They therefore confer a much broader
      predisposition to infections than that for IRAK-4 and MyD88 deficiencies. These
      disorders were initially thought to be rare but have now been diagnosed in over
      170 patients worldwide. We review here the infectious diseases affecting patients
      with inborn errors of NF-kappaB-dependent TLR and IL-1R immunity.

PMID- 21734244
TI  - Mechanisms of obligatory intracellular infection with Anaplasma phagocytophilum.
AB  - Anaplasma phagocytophilum persists in nature by cycling between mammals and
      ticks. Human infection by the bite of an infected tick leads to a potentially
      fatal emerging disease called human granulocytic anaplasmosis. A. phagocytophilum
      is an obligatory intracellular bacterium that replicates inside mammalian
      granulocytes and the salivary gland and midgut cells of ticks. A. phagocytophilum
      evolved the remarkable ability to hijack the regulatory system of host cells. A.
      phagocytophilum alters vesicular traffic to create an intracellular membrane
      bound compartment that allows replication in seclusion from lysosomes. The
      bacterium downregulates or actively inhibits a number of innate immune responses
      of mammalian host cells, and it upregulates cellular cholesterol uptake to
      acquire cholesterol for survival. It also upregulates several genes critical for
      the infection of ticks, and it prolongs tick survival at freezing temperatures.
      Several host factors that exacerbate infection have been identified, including
      interleukin-8 (IL-8) and cholesterol. Host factors that overcome infection
      include IL-12 and gamma interferon (IFN-gamma). Two bacterial type IV secretion
      effectors and several bacterial proteins that associate with inclusion membranes
      have been identified. An understanding of the molecular mechanisms underlying A.
      phagocytophilum infection will foster the development of creative ideas to
      prevent or treat this emerging tick-borne disease.

PMID- 21734246
TI  - Mycoplasma genitalium: from Chrysalis to multicolored butterfly.
AB  - The history, replication, genetics, characteristics (both biological and
      physical), and factors involved in the pathogenesis of Mycoplasma genitalium are
      presented. The latter factors include adhesion, the influence of hormones,
      motility, possible toxin production, and immunological responses. The preferred
      site of colonization, together with current detection procedures, mainly by PCR
      technology, is discussed. The relationships between M. genitalium and various
      diseases are highlighted. These diseases include acute and chronic nongonococcal
      urethritis, balanoposthitis, chronic prostatitis, and acute epididymitis in men
      and urethritis, bacterial vaginosis, vaginitis, cervicitis, pelvic inflammatory
      disease, and reproductive disease in women. A causative relationship, or
      otherwise strong association, between several of these diseases and M. genitalium
      is apparent, and the extent of this, on a subjective basis, is presented; also
      provided is a comparison between M. genitalium and two other genital tract
      orientated mollicutes, namely, Mycoplasma hominis, the first mycoplasma of human
      origin to be discovered, and Ureaplasma species. Also discussed is the
      relationship between M. genitalium and infertility and also arthritis in both men
      and women, as is infection in homosexual and immunodeficient patients. Decreased
      immunity, as in HIV infections, may enhance mycoplasmal detection and increase
      disease severity. Finally, aspects of the antimicrobial susceptibility and
      resistance of M. genitalium, together with the treatment and possible prevention
      of mycoplasmal disease, are discussed.

PMID- 21734247
TI  - Expert systems in clinical microbiology.
AB  - This review aims to discuss expert systems in general and how they may be used in
      medicine as a whole and clinical microbiology in particular (with the aid of
      interpretive reading). It considers rule-based systems, pattern-based systems,
      and data mining and introduces neural nets. A variety of noncommercial systems is
      described, and the central role played by the EUCAST is stressed. The need for
      expert rules in the environment of reset EUCAST breakpoints is also questioned.
      Commercial automated systems with on-board expert systems are considered, with
      emphasis being placed on the "big three": Vitek 2, BD Phoenix, and MicroScan. By
      necessity and in places, the review becomes a general review of automated system
      performances for the detection of specific resistance mechanisms rather than
      focusing solely on expert systems. Published performance evaluations of each
      system are drawn together and commented on critically.

PMID- 21734250
TI  - Light microscopic sciatic nerve changes in control beagle dogs from toxicity
      studies.
AB  - Although the dog is a common choice among nonrodent species in evaluation of
      compound safety for regulatory submission, information regarding the incidence of
      spontaneous or incidental microscopic changes in canine peripheral nerve is
      limited. A retrospective examination was performed of routine histologic
      preparations of sciatic nerve from eighty-one control dogs in toxicity studies
      ranging from ten days to three months in duration. Spontaneous background changes
      included digestion chambers, foci of vacuolation, nerve fibers circumscribed by
      proliferating Schwann cells (bands of Bungner), and small foci of myelin
      aggregation. The latter accounted for 91% of the microscopic changes and were
      noted in all sections examined. These changes were quantified, and the number per
      square millimeter of evaluable nerve tissue was determined for each slide.
      Densities of foci varied among the slides examined; no age- or sex-related trends
      were apparent. In addition, anatomic features of peripheral nerves including
      nodes of Ranvier, Schmidt-Lanterman incisures, Renaut bodies, and effects
      resulting from sectioning plane were noted. By demonstrating the range of effects
      observed within control animals, these observations provide a basis for
      recognition of possible compound-related effects in routine nerve preparations
      from dogs included in toxicity studies.

PMID- 21734251
TI  - Acetaminophen-induced forestomach lesion in normal rats following intravenous
      exposure.
AB  - Four groups of ten male and ten female rats each were treated intravenously with
      saline, 400 mg/kg/day of a commercially available injectable acetaminophen
      formulation, or 400 mg/kg/day of a new injectable acetaminophen formulation with
      (aged) or without (fresh) impurities daily for fourteen days. Gross observations
      of the mucosal surface of the stomachs from treated rats included multifocal to
      diffuse pale, elevated foci confined to the nonglandular region of the stomach.
      Treatment-related histologic observations consisted of epithelial hyperplasia and
      hyperkeratosis of the nonglandular mucosa of the stomach. The epithelial
      hyperplasia was characterized by a thickened epithelium, frequently accompanied
      by the development of undulations at the basement membrane zone, resulting in the
      formation of rete ridgelike structures protruding into the underlying tissue. The
      submucosa was usually expanded by edema and occasionally contained an infiltrate
      of neutrophils, eosinophils, and macrophages. The hyperplasia was usually
      accompanied by hyperkeratosis resulting in thickening of the stratum corneum. The
      incidence and severity of the gastric changes were similar across all treatment
      regimens. Although considered clinically irrelevant since humans do not have a
      forestomach equivalent, these results are significant in that this appears to be
      the first report of forestomach hyperplasia and hyperkeratosis following
      intravenous exposure to acetaminophen.

PMID- 21734252
TI  - Understanding otherness: the neural bases of action comprehension and pain
      empathy in a congenital amputee.
AB  - How do we understand and empathize with individuals whose bodies are drastically
      different from our own? We investigated the neural processes by which an
      individual with a radically different body, a congenital amputee who is born
      without limbs, engages her own sensory-motor representations as a means to
      understand other people's body actions or emotional states. Our results support
      the prediction that when the goal of the action is possible for the observer,
      one's own motor regions are involved in processing action observation, just as
      when individuals viewed those similar to themselves. However, when the observed
      actions are not possible, mentalizing mechanisms, relying on a different set of
      neural structures, are additionally recruited to process the actions.
      Furthermore, our results indicate that when individuals view others experiencing
      pain in body parts that they have, the insula and somatosensory cortices are
      activated, consistent with previous reports. However, when an individual views
      others experiencing pain in body parts that she does not have, the insula and
      secondary somatosensory cortices are still active, but the primary somatosensory
      cortices are not. These results provide a novel understanding for how we
      understand and empathize with individuals who drastically differ from the self.

PMID- 21734253
TI  - Functional ADA polymorphism increases sleep depth and reduces vigilant attention
      in humans.
AB  - Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM)
      sleep may reflect synaptic changes across the sleep-wake continuum and the
      restorative function of sleep. The nonsynonymous c.22G>A polymorphism
      (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to
      inosine and predicts baseline differences in sleep slow-wave oscillations. We
      hypothesized that this polymorphism affects cognitive functions, and investigated
      whether it modulates electroencephalogram (EEG), behavioral, subjective, and
      biochemical responses to sleep deprivation. Attention, learning, memory, and
      executive functioning were quantified in healthy adults. Right-handed carriers of
      the variant allele (G/A genotype, n = 29) performed worse on the d2 attention
      task than G/G homozygotes (n = 191). To test whether this difference reflects
      elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep
      deprivation were studied in 2 prospectively matched groups of G/A and G/G
      genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM
      sleep were significantly higher in G/A than in G/G genotype. Moreover, attention
      and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz),
      sleepiness, fatigue, and alpha-amylase in saliva were enhanced. These convergent
      data demonstrate that genetic reduction of ADA activity elevates sleep pressure
      and plays a key role in sleep and waking quality in humans.

PMID- 21734248
TI  - Pathogenesis and pathophysiology of pneumococcal meningitis.
AB  - Pneumococcal meningitis continues to be associated with high rates of mortality
      and long-term neurological sequelae. The most common route of infection starts by
      nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal
      entrapment and evade the host immune system after local activation. During
      invasive disease, pneumococcal epithelial adhesion is followed by bloodstream
      invasion and activation of the complement and coagulation systems. The release of
      inflammatory mediators facilitates pneumococcal crossing of the blood-brain
      barrier into the brain, where the bacteria multiply freely and trigger activation
      of circulating antigen-presenting cells and resident microglial cells. The
      resulting massive inflammation leads to further neutrophil recruitment and
      inflammation, resulting in the well-known features of bacterial meningitis,
      including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema,
      hydrocephalus, and cerebrovascular complications. Experimental animal models
      continue to further our understanding of the pathophysiology of pneumococcal
      meningitis and provide the platform for the development of new adjuvant
      treatments and antimicrobial therapy. This review discusses the most recent views
      on the pathophysiology of pneumococcal meningitis, as well as potential targets
      for (adjunctive) therapy.

PMID- 21734254
TI  - Effect of multimedia information sequencing on educational outcome in orthodontic
      training.
AB  - The aim of this research was to compare the effectiveness of hierarchical
      sequencing (HS) versus elaboration sequencing (ES) models in improving
      educational outcome of clinical knowledge when using instructional multimedia
      programs in postgraduate orthodontic training. Twenty-four postgraduate and 24
      undergraduate dental students participated in this study. The postgraduates were
      following an orthodontic speciality training programme. The undergraduates were
      fourth- and fifth-year dental students. Twelve instructional multimedia modules
      were developed, six logically sequenced (LS) discussing six different orthodontic
      topics. Another six modules on identical topics were sequenced according to one
      macro-sequencing (MS) model. The implemented MS model was either HS or ES. The
      only difference between LS and MS modules was the adopted sequencing model. All
      participants were assigned into consistent pairs of students and were randomly
      divided into a test and a control group. In each pair, one student studied the LS
      module (control group) while the other studied the MS version (test group). Pre-
      and post-evaluation tests of each pair of participants were performed to measure
      knowledge, understanding and application of each participant with regard to the
      discussed topic. A multilevel analysis was conducted to assess the estimated
      effect of the different sequencing models. The level of significance was set at
      0.05.  At baseline, no significant differences (P > 0.05) were found in pre-test
      scores between groups. The HS model showed a significant effect on the scores
      achieved (P = 0.05). The test group showed a significantly higher estimated
      probability of correct answers to the questions (P = 0.003) when applying the HS
      model. The HS model may improve educational outcome when using instructional
      multimedia programs in postgraduate orthodontic training.

PMID- 21734249
TI  - Pathogenesis of chagas' disease: parasite persistence and autoimmunity.
AB  - Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected
      individuals can die of Chagas' disease. The transfer of the parasite
      mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic
      patients can explain the pathogenesis of the disease; in cases of Chagas' disease
      with evident cardiomyopathy, the kDNA minicircles integrate mainly into
      retrotransposons at several chromosomes, but the minicircles are also detected in
      coding regions of genes that regulate cell growth, differentiation, and immune
      responses. An accurate evaluation of the role played by the genotype alterations
      in the autoimmune rejection of self-tissues in Chagas' disease is achieved with
      the cross-kingdom chicken model system, which is refractory to T. cruzi
      infections. The inoculation of T. cruzi into embryonated eggs prior to incubation
      generates parasite-free chicks, which retain the kDNA minicircle sequence mainly
      in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations
      to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy
      in adult life and die of heart failure. The phenotyping of the lesions revealed
      that cytotoxic CD45, CD8(+) gammadelta, and CD8alpha(+) T lymphocytes carry out
      the rejection of the chicken heart. These results suggest that the inflammatory
      cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.

PMID- 21734255
TI  - Cone-beam computed tomography evaluation of relationship between tongue volume
      and lower incisor irregularity.
AB  - The aim of this study was to evaluate the relationship between the tongue volume
      and lower incisor irregularity, using cone-beam computed tomography (CBCT), and
      to identify the possible gender differences. CBCT images of 60 patients between
      16 and 36 years of age were selected from 1400 sets of images in the database.
      Tomography was carried out using iCAT(r) (Imaging Sciences International,
      Hatfield, Pennsylvania, USA) and segmentation was carried out by using Mimics
      10.1 software (Materialise NV, Leuven, Belgium). The tongue volume was calculated
      by using the volume of the voxels from the scan and the number of voxels selected
      for a given mask. Lower incisor crowding was measured with the Little's
      irregularity index and divided into three groups: mild, moderate, and severe.
      Independent samples t-test, analysis of variance (ANOVA), and Tukey test were
      used at P < 0.05 level. Pearson correlation coefficients and linear regression
      model were calculated to determine the correlation between tongue volume and
      incisor irregularity. No significant gender dimorphism was found for the tongue
      volume (females: 28.13 +/- 8.54 cm(3) and males: 31.02 +/- 9.75 cm(3)). According
      to ANOVA, there was statistically significant difference in the tongue volume
      measurements among subjects with different levels of irregularity. Tukey analysis
      indicated that mild irregularity group (33.97 cm(3)) showed higher values for
      tongue volume than severe irregularity group (26.60 cm(3); P = 0.025). The
      relationship between incisor irregularity and tongue volume was evaluated for
      both genders and significant inverse correlation (r = -0.429; P = 0.029) was
      determined between lower incisor irregularity and tongue volume in males. In
      female group, no significant correlation was determined between tongue volume and
      incisor irregularity. 

PMID- 21734256
TI  - Urinary levels of the tobacco-specific carcinogen N'-nitrosonornicotine and its
      glucuronide are strongly associated with esophageal cancer risk in smokers.
AB  - N'-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) are tobacco-specific nitrosamines. NNN and NNK can induce cancers of the
      esophagus and lung, respectively, in laboratory animals, but data on human
      esophageal cancer are lacking. The association between levels of NNN and 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), an NNK metabolite, in urine
      samples collected before diagnosis and risk of esophageal cancer was examined in
      77 patients with esophageal cancer and 223 individually matched controls, all
      current smokers, from a cohort of 18244 Chinese men in Shanghai, China, followed
      from 1986 to 2008. Urinary total NNN (free NNN plus NNN-N-glucuronide) was
      significantly higher, whereas the percentage of its detoxification product NNN-N
      glucuronide was significantly lower in cases than controls. Odds ratios (95%
      confidence intervals) of esophageal cancer for the second and third tertiles of
      total NNN were 3.99 (1.25-12.7) and 17.0 (3.99-72.8), respectively, compared with
      the first tertile after adjustment for urinary total NNAL and total cotinine and
      smoking intensity and duration (P(trend) < 0.001). The corresponding figures for
      the percentage of NNN-N-glucuronides were 0.37 (0.17-0.80) and 0.27 (0.11-0.62)
      (P(trend) = 0.001). Urinary total NNN and the percentage of NNN-N-glucuronides
      almost completely accounted for the observed association for urinary total NNAL
      (free NNAL plus its glucuronides), urinary total cotinine and smoking intensity
      with esophageal cancer risk. These findings along with results of previous
      studies in laboratory animals support a significant and unique role of NNN in
      esophageal carcinogenesis in humans.

PMID- 21734257
TI  - Neutralizing mutations of carboxylates that bind metal 2 in T5 flap endonuclease
      result in an enzyme that still requires two metal ions.
AB  - Flap endonucleases (FENs) are divalent metal ion-dependent phosphodiesterases.
      Metallonucleases are often assigned a "two-metal ion mechanism" where both metals
      contact the scissile phosphate diester. The spacing of the two metal ions
      observed in T5FEN structures appears to preclude this mechanism. However, the
      overall reaction catalyzed by wild type (WT) T5FEN requires three Mg(2+) ions,
      implying that a third ion is needed during catalysis, and so a two-metal ion
      mechanism remains possible. To investigate the positions of the ions required for
      chemistry, a mutant T5FEN was studied where metal 2 (M2) ligands are altered to
      eliminate this binding site. In contrast to WT T5FEN, the overall reaction
      catalyzed by D201I/D204S required two ions, but over the concentration range of
      Mg(2+) tested, maximal rate data were fitted to a single binding isotherm.
      Calcium ions do not support FEN catalysis and inhibit the reactions supported by
      viable metal cofactors. To establish participation of ions in stabilization of
      enzyme-substrate complexes, dissociation constants of WT and D201I/D204S
      substrate complexes were studied as a function of [Ca(2+)]. At pH 9.3 (maximal
      rate conditions), Ca(2+) substantially stabilized both complexes. Inhibition of
      viable cofactor supported reactions of WT, and D201I/D204S T5FENs was biphasic
      with respect to Ca(2+) and ultimately dependent on 1/[Ca(2+)](2). By varying the
      concentration of viable metal cofactor, Ca(2+) ions were shown to inhibit
      competitively displacing two catalytic ions. Combined analyses imply that M2 is
      not involved in chemical catalysis but plays a role in substrate binding, and
      thus a two-metal ion mechanism is plausible.

PMID- 21734258
TI  - Relaxin modulates proinflammatory cytokine secretion from human decidual
      macrophages.
AB  - Relaxin (RLN) is a systemic hormone from the corpus luteum, and its levels remain
      low during normal human gestation. Indeed, elevation of circulating RLN has long
      been associated with preterm birth, for which there has been no physiological
      explanation. Recent studies have shown that RLN suppresses endotoxin-induced
      cytokine secretion from THP-1 monocytic cells by acting on the glucocorticoid
      receptor (GR), but its effects on primary macrophages are unknown. Therefore, in
      the present study, we examined the effects of RLN on cytokine secretion from
      primary decidual macrophages (DMs) obtained at term before labor. Unlike THP-1
      cells, RLN had no effects on the cytokine responses induced by either
      lipopolysaccharide (LPS) or interleukin (IL) 1B, mimicking infection-induced or
      sterile inflammation, respectively. However, RLN alone for 4 h significantly
      decreased (P < 0.05) colony-stimulating factor 2 (CSF2; also known as granulocyte
      macrophage colony-stimulating factor) and IL8 but for 24 h significantly
      increased IL6 (P < 0.01). We show that DMs express both the RLN receptor (RXFP1)
      and the GR. RLN suppression of CSF2 and IL8 was sensitive to the GR-antagonist
      mifepristone (RU-486). However, RLN activation of RXFP1 induced a dose-dependent
      cAMP response, which when mimicked by forskolin also caused significantly
      increased (P < 0.05) secretion of IL6. Thus, RLN may be anti-inflammatory in DMs
      via activation of the GR but proinflammatory via activation of RXFP1 and cAMP. In
      summary, we have shown that RLN targeting DMs may modulate proinflammatory
      cytokine secretion at the maternal-fetal interface and contribute to the
      localized inflammatory response associated with parturition in women.

PMID- 21734259
TI  - Uterine gland formation in mice is a continuous process, requiring the ovary
      after puberty, but not after parturition.
AB  - Uterine gland formation occurs postnatally in an ovary- and steroid-independent
      manner in many species, including humans. Uterine glands secrete substances that
      are essential for embryo survival. Disruption of gland development during the
      postnatal period prevents gland formation, resulting in infertility.
      Interestingly, stabilization of beta-catenin (CTNNB1) in the uterine stroma
      causes a delay in gland formation rather than a complete absence of uterine
      glands. Thus, to determine if a critical postnatal window for gland development
      exists in mice, we tested the effects of extending the endocrine environment of
      pregnancy on uterine gland formation by treating neonatal mice with estradiol,
      progesterone, or oil for 5 days. One uterine horn was removed before puberty, and
      the other was collected at maturity. Some mice were also ovariectomized before
      puberty. The hormone-treated mice exhibited a delay in uterine gland formation.
      Hormone-treatment increased the abundance of uterine CTNNB1 and estrogen receptor
      alpha (ESR1) before puberty, indicating possible mechanisms for delayed gland
      formation. Despite having fewer glands, progesterone-treated mice were fertile,
      suggesting that a threshold number of glands is required for pregnancy. Mice that
      were ovariectomized before puberty did not undergo further uterine growth or
      gland development. Finally, to establish the role of the ovary in postpartum
      uterine gland regeneration, mice were either ovariectomized or given a sham
      surgery after parturition, and uteri were evaluated 1 wk later. We found that the
      ovary is not required for uterine growth or gland development following
      parturition. Thus, uterine gland development occurs continuously in mice and
      requires the ovary after puberty, but not after parturition.

PMID- 21734260
TI  - Identification of CEACAM6 as an intermediate filament-associated protein
      expressed in Sertoli cells of rat testis.
AB  - Ceacam6 (carcinoembryonic antigen-related cell adhesion molecule 6 gene) has
      recently been isolated by differential display followed by RT-PCR and DNA
      sequence analyses. Ceacam6 is a member of an immunoglobulin superfamily and
      encodes a protein of 266 amino acid residues possessing one immunoglobulin (Ig)
      like domain. RT-PCR analysis showed that Ceacam6 was dominantly expressed in rat
      testis and its expression level prominently increased after 6 wk of postnatal
      development in testis. Immunohistochemical analyses using the anti-CEACAM6
      antibody revealed that CEACAM6 colocalized with intermediate filaments (vimentin)
      in Sertoli cells and interstitial cells. The association between CEACAM6 and
      vimentin was observed throughout postnatal development in rat testis.
      Transfection experiments performed in COS-7 cells suggested that overexpression
      of CEACAM6 brought about aggregation of vimentin filament around nuclei with
      which CEACAM6 colocalized and that the N-terminus region of CEACAM6, including
      the Ig-like domain, seemed to be required for association with vimentin
      filaments. Interaction between CEACAM6 and vimentin in rat testis and transfected
      COS-7 cells was confirmed by immunoprecipitation. Our observations strongly
      suggested that CEACAM6 might be a novel intermediate filament-associated protein
      involved in regulation of vimentin architecture in Sertoli cells.

PMID- 21734261
TI  - Spatiotemporal expression of bone morphogenetic protein family ligands and
      receptors in the zebrafish ovary: a potential paracrine-signaling mechanism for
      oocyte-follicle cell communication.
AB  - The bone morphogenetic proteins (BMPs), originally identified by their abilities
      to induce bone and/or cartilage formation, have been reported to be involved in
      various growth and differentiation processes, including reproduction. Although
      mammalian models are more frequently used to study the BMP system in
      reproduction, we have extended the study to the zebrafish, an excellent model for
      studying female reproduction in teleosts. Reverse transcription-PCR analysis
      revealed the expression of the Bmp ligands (bmp2a, bmp2b, bmp4, bmp6, and bmp7a)
      and the type II Bmp receptors (bmpr2a and bmpr2b) in various tissues, including
      the ovary. Spatiotemporal distribution of these Bmp ligands and receptors in the
      ovary was then investigated in this study. Reverse transcription-PCR on isolated
      follicle layers and denuded oocytes demonstrated that all Bmp ligands examined
      were exclusively or abundantly expressed in the oocyte, whereas the two receptors
      were expressed exclusively in the follicle layers, strongly suggesting a
      potential paracrine signaling from the oocyte towards the follicle layer by
      various Bmp ligands. This supports the current view that instead of being
      passively controlled and nurtured by the follicle layer for its growth and
      development, the oocyte may play an active role by releasing various growth
      differentiation factors to regulate follicle layer function. Quantitative
      analysis of temporal expression profiles during folliculogenesis revealed an
      increased expression of bmp2a, bmp2b, bmp4, and bmp6 from primary growth (stage
      I) to previtellogenic (stage II) stages, followed by steady declines toward the
      end of folliculogenesis when the follicles became fully grown. On the contrast,
      the BMP receptors (bmpr2a and bmpr2b) consistently showed an increase in
      expression during folliculogenesis, with the peak levels reached at the full
      grown stage prior to final oocyte maturation. The spatiotemporal expression
      patterns of the Bmp family in the zebrafish follicles provide important insights
      into potential roles for Bmps during follicle development as oocyte-derived
      factors. Further experiments using recombinant zebrafish Bmp4 showed that Bmp4
      had an inhibitory effect on spontaneous oocyte maturation in vitro, but not
      17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP)-induced oocyte maturation in
      vitro.

PMID- 21734262
TI  - Upstream stimulatory factor induces Nr5a1 and Shbg gene expression during the
      onset of rat Sertoli cell differentiation.
AB  - Within the testis, each Sertoli cell can support a finite number of developing
      germ cells. During development, the cessation of Sertoli cell proliferation and
      the onset of differentiation establish the final number of Sertoli cells and,
      thus, the total number of sperm that can be produced. The upstream stimulatory
      factors 1 and 2 (USF1 and USF2, respectively) differentially regulate numerous
      Sertoli cell genes during differentiation. To identify genes that are activated
      by USF proteins during differentiation, studies were conducted in Sertoli cells
      isolated from 5- and 11-day-old rats, representing proliferating and
      differentiating cells, respectively. Usf1 mRNA and USF1 protein levels were
      increased between 5 and 11 days after birth. In vitro studies revealed that USF1
      and USF2 DNA-binding activity also increased at 11 days for the promoters of four
      potential target genes, Fshr, Gata4, Nr5a1, and Shbg. Chromatin
      immunoprecipitation assays confirmed that USF recruitment increased in vivo
      between 5 and 11 days after birth at the Fshr, Gata4, and Nr5a1 promoters.
      Expression of Nr5a1 and Shbg, but not of Fshr or Gata4, mRNAs was elevated in 11
      day-old Sertoli cells compared with 5-day-old Sertoli cells. Transient
      transfection of USF1 and USF2 expression vectors up-regulated Nr5a1 and Shbg
      promoter activity. RNA interference assays demonstrated that USF1 and USF2
      contribute to Nr5a1 and Shbg expression in differentiating cells. Together, these
      data indicate that increased USF levels induce the expression of Nr5a1 and Shbg
      during the differentiation of Sertoli cells, whereas Fshr and Gata4 expression is
      not altered by USF proteins during differentiation.

PMID- 21734263
TI  - Bezafibrate restores the inhibition of FSH-induced follicular development and
      steroidogenesis by tumor necrosis factor-alpha through peroxisome proliferator
      activated receptor-gamma pathway in an in vitro mouse preantral follicle culture.
AB  - We recently reported that bezafibrate, a lipid-lowering drug of the fibrate
      class, administered in addition to clomiphene citrate (CC) successfully induced
      ovulation in CC-resistant polycystic ovary syndrome (PCOS) patients. We
      hypothesized that bezafibrate may directly affect ovarian follicle development.
      Insulin resistance and compensatory hyperinsulinemia are important for the
      pathogenesis of PCOS. In this study, we first examined the effects of tumor
      necrosis factor-alpha (TNF), which plays a role in insulin resistance, on
      follicle development by using the follicle culture system. TNF significantly
      inhibited follicle-stimulating hormone (FSH)-induced follicle development, 17beta
      estradiol (E2) secretion, and ovulation rate in a dose-dependent manner. We then
      examined whether bezafibrate treatment could rescue the inhibition of FSH-induced
      follicle development and steroidogenesis by TNF. Bezafibrate treatment rescued
      inhibition of follicle development, secretion of E2, and ovulation rate by TNF.
      We examined the expression of peroxisome proliferator-activated receptor (PPAR)
      subtypes in mouse preantral follicles. As the protein expression of only PPARG
      was observed in mouse preantral follicles, we examined whether bezafibrate could
      affect follicle development and steroidogenesis through PPARG pathways. Treatment
      with GW1929, a selective PPARG agonist, restored inhibition of FSH-induced
      follicle development and steroidogenesis by TNF, whereas treatment with GW9662, a
      selective PPARG antagonist, canceled the restorative effects of bezafibrate.
      Collectively, the results in this study suggest that bezafibrate may directly
      exhibit a restorative effect on the inhibition of ovarian follicle development
      and steroidogenesis by TNF through the PPARG pathway.

PMID- 21734264
TI  - Expression of Tubb3, a beta-tubulin isotype, is regulated by androgens in mouse
      and rat Sertoli cells.
AB  - Our previous analysis of Sertoli cell androgen receptor (AR) knockout (SCARKO)
      mice revealed that several cytoskeletal components are a potential target of
      androgen action. Here, we found that one of these components, the beta-tubulin
      isotype Tubb3, is differentially regulated in testes from SCARKO mice (relative
      to littermate controls) from Postnatal Day 10 to adulthood. The Tubb3 gene is
      unique in this respect, as at Day 10, no other beta-tubulin genes are
      significantly regulated by AR. We further characterized androgen regulation of
      Tubb3 in vivo and in vitro and demonstrated that it is a conserved feature in
      both mice and rats. To investigate whether androgens directly regulate Tubb3
      expression, we screened for androgen response elements (AREs) in the Tubb3 gene.
      In silico analysis revealed the presence of four ARE motifs in Tubb3 intron 1,
      two of which bind to AR in vitro. Mutation of one of these (ARE1) strongly
      reduced androgen-dependent reporter gene expression. These results, coupled with
      the finding that the AR binds to the Tubb3 ARE region in vivo, suggest that Tubb3
      is a direct target of AR. Our data strengthen the contention that androgens exert
      their effects on spermatogenesis, in part, through modulation of the Sertoli cell
      cytoskeleton. Androgen regulation of beta-tubulin has also been described in
      neurons, fortifying the already known similarity in microtubule organization in
      Sertoli cell processes and neurons, the only other cell type in which Tubb3 is
      known to be expressed.

PMID- 21734265
TI  - Generation of colonies of induced trophoblast cells during standard reprogramming
      of porcine fibroblasts to induced pluripotent stem cells.
AB  - During reprogramming of porcine mesenchymal cells with a four-factor
      (POU5F1/SOX2/KLF4/MYC) mixture of vectors, a fraction of the colonies had an
      atypical phenotype and arose earlier than the recognizable porcine induced
      pluripotent stem (iPS) cell colonies. Within days after each passage, patches of
      cells with an epithelial phenotype formed raised domes, particularly under 20%
      O(2) conditions. Relative to gene expression of the iPS cells, there was up
      regulation of genes for transcription factors associated with trophoblast (TR)
      lineage emergence, e.g., GATA2, PPARG, MSX2, DLX3, HAND1, GCM1, CDX2, ID2, ELF5,
      TCFAP2C, and TEAD4 and for genes required for synthesis of products more typical
      of differentiated TR, such as steroids (HSD17B1, CYP11A1, and STAR), pregnancy
      associated glycoproteins (PAG6), and select cytokines (IFND, IFNG, and IL1B).
      Although POU5F1 was down-regulated relative to that in iPS cells, it was not
      silenced in the induced TR (iTR) cells over continued passage. Like iPS cells,
      iTR cells did not senesce on extended passage and displayed high telomerase
      activity. Upon xenografting into immunodeficient mice, iTR cells formed
      nonhemorrhagic teratomas composed largely of layers of epithelium expressing TR
      markers. When cultured under conditions that promoted embryoid body formation,
      iTR cells formed floating spheres consisting of a single epithelial sheet whose
      cells were tethered laterally by desmosome-like structures. In conclusion,
      reprogramming of porcine fibroblasts to iPS cells generates, as a by-product,
      colonies composed of self-renewing populations of TR cells, possibly containing
      TR stem cells.

PMID- 21734266
TI  - Identification of hepsin and protein disulfide isomerase A3 as targets of
      gelatinolytic action in rat ovarian granulosa cells during the periovulatory
      period.
AB  - The matrix metalloproteinase (MMP) family is believed to play a role in the
      ovulatory process because MMP inhibitors block oocyte release. However, little is
      known about the mechanisms by which the MMPs affect ovulation. The present study
      investigated the degradomic actions of the gelatinases, MMP2 and MMP9, by
      identifying gelatinolytic targets in periovulatory granulosa cells. Granulosa
      cells were collected from immature rats 48 h after equine chorionic gonadotropin
      treatment and were cultured with human chorionic gonadotropin (hCG) in the
      absence or presence of a specific MMP2/9 inhibitor ((2R)-2-[(4
      biphenylylsulfonyl)amino]-3-phenylpropionic acid) for an additional 24 h. The
      conditioned media was analyzed for gelatinolytic activity, progesterone, and
      peptide profiles. Gelatinolytic activity and progesterone were induced in
      response to hCG; however, there was no difference in progesterone between cells
      treated with or without the inhibitor. Peptide fragments of proteins altered in
      the presence of the gelatinase inhibitor were identified by two-dimensional gel
      electrophoresis and mass spectrometry. Protein disulfide isomerase A3 (PDIA3),
      which plays a role in protein folding, was identified as a peptide that decreased
      in the presence of inhibitor while the serine protease hepsin, was found to
      increase with inhibitor treatment. Subsequent experiments established that PDIA3
      and hepsin were targets of MMP2/9 action by cleavage with MMP2 and Western blot
      analysis, respectively. Additionally, hepsin was identified as a gelatinolytic
      target in ovarian cancer cells. In the present study, proteomics has identified
      proteins that may be involved in novel ways in the complex cascades that are
      mediated by gelatinolytic MMPs during the periovulatory period.

PMID- 21734267
TI  - Does a nonclassical signaling mechanism underlie an increase of estradiol
      mediated gonadotropin-releasing hormone receptor binding in ovine pituitary
      cells?
AB  - Estradiol-17beta (E2) is the major regulator of GnRH receptor (GnRHR) gene
      expression and number during the periovulatory period; however, the mechanisms
      underlying E2 regulation of the GNRHR gene remain undefined. Herein, we find that
      E2 conjugated to BSA (E2-BSA) mimics the stimulatory effect of E2 on GnRH binding
      in primary cultures of ovine pituitary cells. The time course for maximal GnRH
      analog binding was similar for both E2 and E2-BSA. The ability of E2 and E2-BSA
      to increase GnRH analog binding was blocked by the estrogen receptor (ER)
      antagonist ICI 182,780. Also, increased GnRH analog binding in response to E2 and
      the selective ESR1 agonist propylpyrazole triol was blocked by expression of a
      dominant-negative form of ESR1 (L540Q). Thus, membrane-associated ESR1 is the
      likely candidate for mediating E2 activation of the GNRHR gene. As cAMP response
      element binding protein (CREB) is an established target for E2 activation in
      gonadotrophs, we next explored a potential role for this protein as an
      intracellular mediator of the E2 signal. Consistent with this possibility,
      adenoviral-mediated expression of a dominant-negative form of CREB (A-CREB)
      completely abolished the ability of E2 to increase GnRH analog binding in primary
      cultures of ovine pituitary cells. Finally, the presence of membrane-associated
      E2 binding sites on ovine pituitary cells was demonstrated using a fluorescein
      isothiocyanate conjugate of E2-BSA. We suggest that E2 regulation of GnRHR number
      during the preovulatory period reflects a membrane site of action and may proceed
      through a nonclassical signaling mechanism, specifically a CREB-dependent
      pathway.

PMID- 21734268
TI  - Synergistic regulation of human oxytocin receptor promoter by CCAAT/ enhancer
      binding protein and RELA.
AB  - Uterine activation is associated with increased oxytocin receptor (OXTR)
      expression and myometrial sensitivity to oxytocin. The OXTR promoter contains
      binding sites for CCAAT/enhancer-binding protein (CEBP) and nuclear factor-kappa
      B p65 (RELA). RELA and CEBP beta (CEBPB) play a synergistic role in OXTR promoter
      activation. We created deletions in a DNA construct consisting of 850 bp upstream
      of the transcription start site linked to luc reporter to identify the CIS
      element of the OXTR promoter responsible for the synergistic activation by RELA
      and CEBPB. Deletion from -712 to -692 bp eliminated synergy, demonstrating that
      the critical region lies within these 20 bp. Binding studies showed that this
      sequence binds both RELA and CEBPB. The 20-bp critical region for synergistic
      activation of OXTR requires full-length RELA but only the basic leucine zipper
      domain of CEBPB.

PMID- 21734269
TI  - LRRK2: a problem lurking in vesicle trafficking?

PMID- 21734270
TI  - Brn3a and Islet1 act epistatically to regulate the gene expression program of
      sensory differentiation.
AB  - The combinatorial expression of transcription factors frequently marks cellular
      identity in the nervous system, yet how these factors interact to determine
      specific neuronal phenotypes is not well understood. Sensory neurons of the
      trigeminal ganglion (TG) and dorsal root ganglia (DRG) coexpress the homeodomain
      transcription factors Brn3a and Islet1, and past work has revealed partially
      overlapping programs of gene expression downstream of these factors. Here we
      examine sensory development in Brn3a/Islet1 double knock-out (DKO) mice. Sensory
      neurogenesis and the formation of the TG and DRG occur in DKO embryos, but the
      DRG are dorsally displaced, and the peripheral projections of the ganglia are
      markedly disturbed. Sensory neurons in DKO embryos show a profound loss of all
      early markers of sensory subtypes, including the Ntrk neurotrophin receptors, and
      the runt-family transcription factors Runx1 and Runx3. Examination of global gene
      expression in the E12.5 DRG of single and double mutant embryos shows that Brn3a
      and Islet1 are together required for nearly all aspects of sensory-specific gene
      expression, including several newly identified sensory markers. On a majority of
      targets, Brn3a and Islet1 exhibit negative epistasis, in which the effects of the
      individual knock-out alleles are less than additive in the DKO. Smaller subsets
      of targets exhibit positive epistasis, or are regulated exclusively by one
      factor. Brn3a/Islet1 double mutants also fail to developmentally repress
      neurogenic bHLH genes, and in vivo chromatin immunoprecipitation shows that
      Islet1 binds to a known Brn3a-regulated enhancer in the neurod4 gene, suggesting
      a mechanism of interaction between these genes.

PMID- 21734271
TI  - Netrin-1-induced local beta-actin synthesis and growth cone guidance requires
      zipcode binding protein 1.
AB  - Local beta-actin synthesis in growth cones of developing axons plays an important
      role in growth cone steering; however, the mRNA binding proteins required for
      this process are unknown. Here we used Zbp1/Imp1(-/)(-) mice to test the
      hypothesis that zipcode binding protein 1 (ZBP1) is required for the regulation
      of beta-actin mRNA transport and local translation underlying growth cone
      guidance. To address the biological function of ZBP1, we developed a novel in
      vitro turning assay with primary cortical neuron balls having axons >1 mm in
      length and demonstrate that growth cones of mammalian neurons exhibit protein
      synthesis-dependent attraction to either netrin-1 or brain-derived neurotrophic
      factor (BDNF). Interestingly, this attraction is lost in Zbp1-deficient neurons.
      Furthermore, BDNF-stimulated beta-actin mRNA localization was attenuated in Zbp1
      deficient neurons, which impaired enrichment of beta-actin protein in the growth
      cone. Finally, using a photoconvertible translation reporter, we found that ZBP1
      is necessary for netrin-1 stimulated local translation of beta-actin mRNA in
      axonal growth cones. Together, these results suggest that netrin-1- and BDNF
      induced growth cone attraction required ZBP1-mediated local translation of beta
      actin mRNA, and therefore ZBP1 regulates protein synthesis-dependent axon
      guidance. Thus, mRNA binding proteins regulating local translation can control
      spatiotemporal protein expression in response to guidance cues and directional
      cell motility.

PMID- 21734272
TI  - Human stereopsis is not limited by the optics of the well-focused eye.
AB  - Human stereopsis, the perception of depth from differences in the two eyes'
      images, is very precise: image differences smaller than a single photoreceptor
      can be converted into a perceived difference in depth. To better understand what
      determines this precision, we examined how the eyes' optics affects stereo
      resolution. We did this by comparing performance with normal, well-focused optics
      and with optics improved by eliminating chromatic aberration and correcting
      higher-order aberrations. We first measured luminance contrast sensitivity in
      both eyes and showed that we had indeed improved optical quality significantly.
      We then measured stereo resolution in two ways: by finding the finest corrugation
      in depth that one can perceive, and by finding the smallest disparity one can
      perceive as different from zero. Our optical manipulation had no effect on stereo
      performance. We checked this by redoing the experiments at low contrast and again
      found no effect of improving optical quality. Thus, the resolution of human
      stereopsis is not limited by the optics of the well-focused eye. We discuss the
      implications of this remarkable finding.

PMID- 21734273
TI  - Movement initiation-locked activity of the anterior putamen predicts future
      movement instability in periodic bimanual movement.
AB  - In periodic bimanual movements, anti-phase-coordinated patterns often change into
      in-phase patterns suddenly and involuntarily. Because behavior in the initial
      period of a sequence of cycles often does not show any obvious errors, it is
      difficult to predict subsequent movement errors in the later period of the
      cyclical sequence. Here, we evaluated performance in the later period of the
      cyclical sequence of bimanual periodic movements using human brain activity
      measured with functional magnetic resonance imaging as well as using initial
      movement features. Eighteen subjects performed a 30 s bimanual finger-tapping
      task. We calculated differences in initiation-locked transient brain activity
      between antiphase and in-phase tapping conditions. Correlation analysis revealed
      that the difference in the anterior putamen activity during antiphase compared
      within-phase tapping conditions was strongly correlated with future instability
      as measured by the mean absolute deviation of the left-hand intertap interval
      during antiphase movements relative to in-phase movements (r = 0.81). Among the
      initial movement features we measured, only the number of taps to establish the
      antiphase movement pattern exhibited a significant correlation. However, the
      correlation efficient of 0.60 was not high enough to predict the characteristics
      of subsequent movement. There was no significant correlation between putamen
      activity and initial movement features. It is likely that initiating unskilled
      difficult movements requires increased anterior putamen activity, and this
      activity increase may facilitate the initiation of movement via the basal ganglia
      thalamocortical circuit. Our results suggest that initiation-locked transient
      activity of the anterior putamen can be used to predict future motor performance.

PMID- 21734274
TI  - Microlesions of the inferior olive reduce vestibular modulation of Purkinje cell
      complex and simple spikes in mouse cerebellum.
AB  - Cerebellar Purkinje cells have two distinct action potentials: complex spikes
      (CSs) are evoked by single climbing fibers that originate from the contralateral
      inferior olive. Simple spikes (SSs) are often ascribed to mossy fiber-granule
      cell-parallel fiber inputs to Purkinje cells. Although generally accepted, this
      view lacks experimental support. Vestibular stimulation independently activates
      primary afferent mossy fibers and tertiary afferent climbing fibers that project
      to the uvula-nodulus (folia 8-10). CSs and SSs normally discharge antiphasically
      during sinusoidal roll-tilt. When CSs increase, SSs decrease. We tested the
      relative independence of these pathways in mice by making electrolytic
      microlesions of the two inferior olivary nuclei from which vestibular climbing
      fibers originate; the beta-nucleus and dorsomedial cell column. This reduced
      vestibular climbing fiber signaling to the contralateral folia 8-10, while
      leaving intact vestibular primary and secondary afferent mossy fibers. We
      recorded from Purkinje cells and interneurons in folia 8-10, identified by
      juxtacellular labeling with Neurobiotin. Microlesions of the inferior olive
      increased the spontaneous discharge of SSs in contralateral folia 8-10, but
      blocked their modulation during vestibular stimulation. The vestibularly evoked
      discharge of excitatory cerebellar interneurons (granule cells and unipolar brush
      cells) was not modified by olivary microlesions. The modulated discharge of
      stellate cells, but not Golgi cells, was reduced by olivary microlesions. We
      conclude that vestibular modulation of CSs and SSs depends on intact climbing
      fibers. The absence of vestibularly modulated SSs following olivary microlesions
      reflects the loss of climbing fiber-evoked stellate cell discharge.

PMID- 21734275
TI  - Pyramidal neurons are "neurogenic hubs" in the neurovascular coupling response to
      whisker stimulation.
AB  - The whisker-to-barrel cortex is widely used to study neurovascular coupling, but
      the cellular basis that underlies the perfusion changes is still largely unknown.
      Here, we identified neurons recruited by whisker stimulation in the rat
      somatosensory cortex using double immunohistochemistry for c-Fos and markers of
      glutamatergic and GABAergic neurons, and investigated in vivo their contribution
      along with that of astrocytes in the evoked perfusion response. Whisker
      stimulation elicited cerebral blood flow (CBF) increases concomitantly with c-Fos
      upregulation in pyramidal cells that coexpressed cyclooxygenase-2 (COX-2) and
      GABA interneurons that coexpressed vasoactive intestinal polypeptide and/or
      choline acetyltransferase, but not somatostatin or parvalbumin. The evoked CBF
      response was decreased by blockade of NMDA (MK-801, -37%), group I metabotropic
      glutamate (MPEP+LY367385, -40%), and GABA-A (picrotoxin, -31%) receptors, but not
      by GABA-B, VIP, or muscarinic receptor antagonism. Picrotoxin decreased stimulus
      induced somatosensory evoked potentials and CBF responses. Combined blockade of
      GABA-A and NMDA receptors yielded an additive decreasing effect (-61%) of the
      evoked CBF compared with each antagonist alone, demonstrating cooperation of both
      excitatory and inhibitory systems in the hyperemic response. Blockade of
      prostanoid synthesis by inhibiting COX-2 (indomethacin, NS-398), expressed by
      ~40% of pyramidal cells but not by astrocytes, impaired the CBF response (-50%).
      The hyperemic response was also reduced (-40%) after inhibition of astroglial
      oxidative metabolism or epoxyeicosatrienoic acids synthesis. These results
      demonstrate that changes in pyramidal cell activity, sculpted by specific types
      of inhibitory GABA interneurons, drive the CBF response to whisker stimulation
      and, further, that metabolically active astrocytes are also required.

PMID- 21734276
TI  - Escalated or suppressed cocaine reward, tegmental BDNF, and accumbal dopamine
      caused by episodic versus continuous social stress in rats.
AB  - The neural link between ostensibly aversive stress experiences and intensely
      rewarding drug taking remains to be delineated. Epidemiological data associate
      stress and the abuse of various drugs, and experimental data identify the
      conditions that determine how episodic social stress intensifies the motivation
      for cocaine and the actual self-administration of cocaine. Two types of social
      stress have been the focus of experimental study in Long-Evans rats, since they
      engender divergent changes in drug- or sugar-rewarded behavior and in
      neuroadaptation. Episodic social defeat stress consists of four brief
      confrontations between the experimental rat and an aggressive resident rat of the
      Long-Evans strain over the course of 10 d. Subordination stress involves the
      continuous exposure to an aggressive resident for 5 weeks, while living in a
      protective cage within the resident's home cage with brief daily confrontations.
      These stress experiences result in (1) increased intravenous cocaine self
      administration under a fixed ratio schedule with prolonged binge-like access in
      episodically defeated intruder rats but suppressed cocaine intake by continuously
      subordinate rats; (2) deteriorated sugar preference and intake and decreased
      exploratory behavior in subordinate, but not intermittently defeated, rats; and
      (3) a sensitized dopamine (DA) response in the nucleus accumbens via in vivo
      microdialysis and increased tegmental brain-derived neural growth factor (BDNF)
      in episodically defeated rats, whereas the continuously subordinate rats show
      suppression of the DA and BDNF responses. These divergent neuroadaptations to
      social stress may represent the substrates for the intensification of cocaine
      "bingeing" relative to the anhedonia-like deterioration of reward processes
      during subordination stress.

PMID- 21734277
TI  - Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a
      mechanism involving activation of axonal phosphotransferases.
AB  - Aggregated filamentous forms of hyperphosphorylated tau (a microtubule-associated
      protein) represent pathological hallmarks of Alzheimer's disease (AD) and other
      tauopathies. While axonal transport dysfunction is thought to represent a primary
      pathogenic factor in AD and other neurodegenerative diseases, the direct
      molecular link between pathogenic forms of tau and deficits in axonal transport
      remain unclear. Recently, we demonstrated that filamentous, but not soluble,
      forms of wild-type tau inhibit anterograde, kinesin-based fast axonal transport
      (FAT) by activating axonal protein phosphatase 1 (PP1) and glycogen synthase
      kinase 3 (GSK3), independent of microtubule binding. Here, we demonstrate that
      amino acids 2-18 of tau, comprising a phosphatase-activating domain (PAD), are
      necessary and sufficient for activation of this pathway in axoplasms isolated
      from squid giant axons. Various pathogenic forms of tau displaying increased
      exposure of PAD inhibited anterograde FAT in squid axoplasm. Importantly,
      immunohistochemical studies using a novel PAD-specific monoclonal antibody in
      human postmortem tissue indicated that increased PAD exposure represents an early
      pathogenic event in AD that closely associates in time with AT8 immunoreactivity,
      an early marker of pathological tau. We propose a model of pathogenesis in which
      disease-associated changes in tau conformation lead to increased exposure of PAD,
      activation of PP1-GSK3, and inhibition of FAT. Results from these studies reveal
      a novel role for tau in modulating axonal phosphotransferases and provide a
      molecular basis for a toxic gain-of-function associated with pathogenic forms of
      tau.

PMID- 21734278
TI  - Asymmetric inhibition of Ulk2 causes left-right differences in habenular neuropil
      formation.
AB  - Studies of the zebrafish epithalamus have provided recent insights into the
      development of left-right brain asymmetry, which is crucial to normal human brain
      function. The habenular nuclei of zebrafish are robustly asymmetric, with dense
      elaboration of neuropil only in the left lateral subnucleus. Because this feature
      is tightly correlated with asymmetric expression of K(+) channel tetramerization
      domain-containing proteins 12.1 and 12.2 (Kctd12.1/12.2), we screened for
      Kctd12.1-interacting proteins to identify molecular mechanisms leading to
      neuropil asymmetry, and uncovered a novel interaction between Kctd12.1 and Unc-51
      like kinase 2 (Ulk2). We show here that knockdown of Ulk2 or overexpression of
      Kctd12 proteins reduces asymmetric neuropil elaboration. Conversely,
      overexpression of Ulk2 or mutation of kctd12 genes causes excess neuropil
      elaboration. We conclude that Ulk2 activity promotes neuropil elaboration while
      Kctd12 proteins limit Ulk2 activity asymmetrically. This work describes a
      regulatory mechanism for neuronal process extension that may be conserved in
      other developmental contexts in addition to the epithalamus.

PMID- 21734279
TI  - Effective connectivity determines the nature of subjective experience in grapheme
      color synesthesia.
AB  - Synesthesia provides an elegant model to investigate neural mechanisms underlying
      individual differences in subjective experience in humans. In grapheme-color
      synesthesia, written letters induce color sensations, accompanied by activation
      of color area V4. Competing hypotheses suggest that enhanced V4 activity during
      synesthesia is either induced by direct bottom-up cross-activation from grapheme
      processing areas within the fusiform gyrus, or indirectly via higher-order
      parietal areas. Synesthetes differ in the way synesthetic color is perceived:
      "projector" synesthetes experience color externally colocalized with a presented
      grapheme, whereas "associators" report an internally evoked association. Using
      dynamic causal modeling for fMRI, we show that V4 cross-activation during
      synesthesia was induced via a bottom-up pathway (within fusiform gyrus) in
      projector synesthetes, but via a top-down pathway (via parietal lobe) in
      associators. These findings show how altered coupling within the same network of
      active regions leads to differences in subjective experience. Our findings
      reconcile the two most influential cross-activation accounts of synesthesia.

PMID- 21734280
TI  - Glial cell line-derived neurotrophic factor reverses alcohol-induced allostasis
      of the mesolimbic dopaminergic system: implications for alcohol reward and
      seeking.
AB  - We previously showed that infusion of glial cell line-derived neurotrophic factor
      (GDNF) into the ventral tegmental area (VTA) rapidly reduces alcohol intake and
      relapse (Carnicella et al., 2008, 2009a), and increases dopamine (DA) levels in
      the nucleus accumbens (NAc) of alcohol-naive rats (Wang et al., 2010). Withdrawal
      from excessive alcohol intake is associated with a reduction in NAc DA levels,
      whereas drug-induced increases in NAc DA levels are associated with reward. We
      therefore tested whether GDNF in the VTA reverses alcohol withdrawal-associated
      DA deficiency and/or possesses rewarding properties. Rats were trained for 7
      weeks to consume high levels of alcohol (5.47 +/- 0.37 g/kg/24 h) in intermittent
      access to 20% alcohol in a two-bottle choice procedure. Using in vivo
      microdialysis, we show that 24 h withdrawal from alcohol causes a substantial
      reduction in NAc DA overflow, which was reversed by intra-VTA GDNF infusion.
      Using conditioned place preference (CPP) paradigm, we observed that GDNF on its
      own does not induce CPP, suggesting that the growth factor is not rewarding.
      However, GDNF blocked acquisition and expression of alcohol-CPP. In addition,
      GDNF induced a downward shift in the dose-response curve for operant self
      administration of alcohol, further suggesting that GDNF suppresses, rather than
      substitutes for, the reinforcing effects of alcohol. Our findings suggest that
      GDNF reduces alcohol-drinking behaviors by reversing an alcohol-induced
      allostatic DA deficiency in the mesolimbic system. In addition, as it lacks abuse
      liability, the study further highlights GDNF as a promising target for treatment
      of alcohol use/abuse disorders.

PMID- 21734281
TI  - The striatum is highly susceptible to mitochondrial oxidative phosphorylation
      dysfunctions.
AB  - Neuronal oxidative phosphorylation (OXPHOS) deficiency has been associated with a
      variety of neurodegenerative diseases, including Parkinson's disease and
      Huntington's disease. However, it is not clear how mitochondrial dysfunction
      alone can lead to a preferential elimination of certain neuronal populations in
      vivo. We compared different types of neuronal populations undergoing the same
      OXPHOS deficiency to determine their relative susceptibility and mechanisms
      responsible for selective neuron vulnerability. We used a mouse model expressing
      a mitochondria-targeted restriction enzyme, PstI or mito-PstI. The expression of
      mito-PstI induces double-strand breaks in the mitochondrial DNA (mtDNA), leading
      to OXPHOS deficiency, mostly due to mtDNA depletion. We targeted mito-PstI
      expression to the cortex, hippocampus, and striatum under the CaMKII-alpha
      promoter. Animals undergoing long-term expression of mito-PstI displayed a
      selective worsening of the striatum over cortical and hippocampal areas. Mito
      PstI expression and mtDNA depletion were not worse in the striatum, but the
      latter showed the most severe defects in mitochondrial membrane potential,
      response to calcium, and survival. These results showed that the striatum is
      particularly sensitive to defects in OXPHOS possibly due to an increased reliance
      on OXPHOS function in this area and differences in response to physiological
      stimuli. These results may help explain the neuropathological features associated
      with Huntington's disease, which have been associated with OXPHOS defects.

PMID- 21734282
TI  - Ethanol enhances neurosteroidogenesis in hippocampal pyramidal neurons by
      paradoxical NMDA receptor activation.
AB  - Using an antibody against 5alpha-reduced neurosteroids, predominantly
      allopregnanolone, we found that immunostaining in the CA1 region of rat
      hippocampal slices was confined to pyramidal neurons. This neurosteroid staining
      was increased following 15 min administration of 60 mm but not 20 mm ethanol, and
      the enhancement was blocked by finasteride and dutasteride, selective inhibitors
      of 5alpha-reductase, a key enzyme required for allopregnanolone synthesis.
      Consistent with a prior report indicating that N-methyl-D-aspartate (NMDA)
      receptor (NMDAR) activation can promote steroid production, we observed that D-2
      amino-5-phosphonovalerate (APV), a competitive NMDAR antagonist, blocked the
      effects of 60 mm ethanol on staining. We previously reported that 60 mm ethanol
      inhibits the induction of long-term potentiation (LTP), a cellular model for
      memory formation, in the CA1 region. In the present study, LTP inhibition by 60
      mm ethanol was also overcome by both the 5alpha-reductase inhibitors and by APV.
      Furthermore, the effects of ethanol on neurosteroid production and LTP were
      mimicked by a low concentration of NMDA (1 MUm), and the ability of NMDA to
      inhibit LTP and to enhance neurosteroid staining was reversed by finasteride and
      dutasteride, as well as by APV. These results indicate that ethanol paradoxically
      enhances GABAergic neurosteroid production by activation of unblocked NMDARs and
      that acute LTP inhibition by ethanol represents a form of NMDAR-mediated
      metaplasticity.

PMID- 21734283
TI  - Deficient CX3CR1 signaling promotes recovery after mouse spinal cord injury by
      limiting the recruitment and activation of Ly6Clo/iNOS+ macrophages.
AB  - Macrophages exert divergent effects in the injured CNS, causing either
      neurotoxicity or regeneration. The mechanisms regulating these divergent
      functions are not understood but can be attributed to the recruitment of distinct
      macrophage subsets and the activation of specific intracellular signaling
      pathways. Here, we show that impaired signaling via the chemokine receptor CX3CR1
      promotes recovery after traumatic spinal cord injury (SCI) in mice. Deficient
      CX3CR1 signaling in intraspinal microglia and monocyte-derived macrophages (MDMs)
      attenuates their ability to synthesize and release inflammatory cytokines and
      oxidative metabolites. Also, impaired CX3CR1 signaling abrogates the recruitment
      or maturation of MDMs with presumed neurotoxic effects after SCI. Indeed, in wild
      type mice, Ly6C(lo)/iNOS(+)/MHCII(+)/CD11c(-) MDMs dominate the lesion site,
      whereas CCR2(+)/Ly6C(hi)/MHCII(-)/CD11c(+) monocytes predominate in the injured
      spinal cord of CX3CR1-deficient mice. Replacement of wild-type MDMs with those
      unable to signal via CX3CR1 resulted in anatomical and functional improvements
      after SCI. Thus, blockade of CX3CR1 signaling represents a selective anti
      inflammatory therapy that is able to promote neuroprotection, in part by reducing
      inflammatory signaling in microglia and MDMs and recruitment of a novel monocyte
      subset.

PMID- 21734284
TI  - Oscillatory alpha-band mechanisms and the deployment of spatial attention to
      anticipated auditory and visual target locations: supramodal or sensory-specific
      control mechanisms?
AB  - Oscillatory alpha-band activity (8-15 Hz) over parieto-occipital cortex in humans
      plays an important role in suppression of processing for inputs at to-be-ignored
      regions of space, with increased alpha-band power observed over cortex
      contralateral to locations expected to contain distractors. It is unclear whether
      similar processes operate during deployment of spatial attention in other sensory
      modalities. Evidence from lesion patients suggests that parietal regions house
      supramodal representations of space. The parietal lobes are prominent generators
      of alpha oscillations, raising the possibility that alpha is a neural signature
      of supramodal spatial attention. Furthermore, when spatial attention is deployed
      within vision, processing of task-irrelevant auditory inputs at attended
      locations is also enhanced, pointing to automatic links between spatial
      deployments across senses. Here, we asked whether lateralized alpha-band activity
      is also evident in a purely auditory spatial-cueing task and whether it had the
      same underlying generator configuration as in a purely visuospatial task. If
      common to both sensory systems, this would provide strong support for
      "supramodal" attention theory. Alternately, alpha-band differences between
      auditory and visual tasks would support a sensory-specific account. Lateralized
      shifts in alpha-band activity were indeed observed during a purely auditory
      spatial task. Crucially, there were clear differences in scalp topographies of
      this alpha activity depending on the sensory system within which spatial
      attention was deployed. Findings suggest that parietally generated alpha-band
      mechanisms are central to attentional deployments across modalities but that they
      are invoked in a sensory-specific manner. The data support an "interactivity
      account," whereby a supramodal system interacts with sensory-specific control
      systems during deployment of spatial attention.

PMID- 21734285
TI  - Primary cilia regulate proliferation of amplifying progenitors in adult
      hippocampus: implications for learning and memory.
AB  - Integration of new neurons into the adult hippocampus has been linked to specific
      types of learning. Primary cilia were found to be required for the formation of
      adult neural stem cells (NSCs) in the hippocampal dentate gyrus during
      development. However, the requirement of cilia in maintenance of adult NSCs is
      unknown. We developed a genetic mouse model in which fetal/perinatal brain
      development is unaffected, but adult hippocampal neurogenesis is constantly
      reduced by conditional ablation of primary cilia in adult GFAP(+) neural
      stem/progenitor cells. We found that this approach specifically reduces the
      number of hippocampal amplifying progenitors (also called type 2a cells) without
      affecting the number of radial NSCs (or type 1 cells). Constant reduction of
      adult hippocampal neurogenesis produced a delay rather than a permanent
      deficiency in spatial learning without affecting the retention of long-term
      memories. Decreased neurogenesis also altered spatial novelty recognition and
      hippocampus-independent cue conditioning. Here, we propose that adult hippocampal
      newborn neurons increase the efficiency of generating the new representations of
      spatial memories and that reduction of adult hippocampal neurogenesis may be
      biased toward cue-based strategies. This novel mouse model provides evidences
      that cognitive deficits associated with ciliary defects (ciliopathies) might be,
      in part, mediated by the deficiency of primary cilia in adult hippocampal
      stem/progenitor cells.

PMID- 21734286
TI  - Bone marrow transplantation augments the effect of brain- and spinal cord
      directed adeno-associated virus 2/5 gene therapy by altering inflammation in the
      murine model of globoid-cell leukodystrophy.
AB  - Globoid-cell leukodystrophy (GLD) is an inherited demyelinating disease caused by
      the deficiency of the lysosomal enzyme galactosylceramidase (GALC). A previous
      study in the murine model of GLD (twitcher) demonstrated a dramatic synergy
      between CNS-directed adeno-associated virus 2/5 (AAV2/5) gene therapy and
      myeloreductive bone marrow transplantation (BMT). However, the mechanism by which
      these two disparate therapeutic approaches synergize is not clear. In addition,
      the therapeutic efficacy may have been limited since the CNS-directed gene
      therapy was restricted to the forebrain and thalamus. In the current study,
      intrathecal and intracerebellar injections were added to the therapeutic regimen
      and the mechanism of synergy between BMT and gene therapy was determined.
      Although AAV2/5 alone provided supraphysiological levels of GALC activity and
      reduced psychosine levels in both the brain and spinal cord, it significantly
      increased CNS inflammation. Bone marrow transplantation alone provided
      essentially no GALC activity to the CNS and did not reduce psychosine levels.
      When AAV2/5 is combined with BMT, there are sustained improvements in motor
      function and the median life span is increased to 123 d (range, 92-282 d)
      compared with 41 d in the untreated twitcher mice. Interestingly, addition of BMT
      virtually eliminates both the disease and AAV2/5-associated inflammatory
      response. These data suggest that the efficacy of AAV2/5-mediated gene therapy is
      limited by the associated inflammatory response and BMT synergizes with AAV2/5 by
      modulating inflammation.

PMID- 21734287
TI  - Impaired auditory temporal selectivity in the inferior colliculus of aged
      Mongolian gerbils.
AB  - Aged humans show severe difficulties in temporal auditory processing tasks (e.g.,
      speech recognition in noise, low-frequency sound localization, gap detection). A
      degradation of auditory function with age is also evident in experimental
      animals. To investigate age-related changes in temporal processing, we compared
      extracellular responses to temporally variable pulse trains and human speech in
      the inferior colliculus of young adult (3 month) and aged (3 years) Mongolian
      gerbils. We observed a significant decrease of selectivity to the pulse trains in
      neuronal responses from aged animals. This decrease in selectivity led, on the
      population level, to an increase in signal correlations and therefore a decrease
      in heterogeneity of temporal receptive fields and a decreased efficiency in
      encoding of speech signals. A decrease in selectivity to temporal modulations is
      consistent with a downregulation of the inhibitory transmitter system in aged
      animals. These alterations in temporal processing could underlie declines in the
      aging auditory system, which are unrelated to peripheral hearing loss. These
      declines cannot be compensated by traditional hearing aids (that rely on
      amplification of sound) but may rather require pharmacological treatment.

PMID- 21734288
TI  - Ready, set, reset: stimulus-locked periodicity in behavioral performance
      demonstrates the consequences of cross-sensory phase reset.
AB  - The simultaneous presentation of a stimulus in one sensory modality often
      enhances target detection in another sensory modality, but the neural mechanisms
      that govern these effects are still under investigation. Here, we test a
      hypothesis proposed in the neurophysiological literature: that auditory
      facilitation of visual-target detection operates through cross-sensory phase
      reset of ongoing neural oscillations (Lakatos et al., 2009). To date, measurement
      limitations have prevented this potentially powerful neural mechanism from being
      directly linked with its predicted behavioral consequences. The present
      experiment uses a psychophysical approach in humans to demonstrate, for the first
      time, stimulus-locked periodicity in visual-target detection, following a
      temporally informative sound. Our data further demonstrate that periodicity in
      behavioral performance is strongly influenced by the probability of audiovisual
      co-occurrence. We argue that fluctuations in visual-target detection result from
      cross-sensory phase reset, both at the moment it occurs and persisting for
      seconds thereafter. The precise frequency at which this periodicity operates
      remains to be determined through a method that allows for a higher sampling rate.

PMID- 21734289
TI  - Post-translational regulation and nuclear entry of TIMELESS and PERIOD are
      affected in new timeless mutant.
AB  - The molecular circadian clock consists of a feedback loop in which canonical
      clock proteins negatively regulate transcription of their own genes. Timed
      nuclear entry of these proteins is critical, but regulation of this event is
      poorly understood. In Drosophila melanogaster, the idea that nuclear entry of
      PERIOD (PER) is controlled by its partner protein TIMELESS (TIM) has been
      challenged by several studies. We identify here a novel mutation in the tim gene
      that eliminates behavioral rhythms while allowing robust expression of TIM and
      PER. Mutant TIM can bind to and stabilize PER. However, neither protein is
      expressed cyclically, and phosphorylation of both is reduced. In addition, TIM
      and PER are localized in the cytoplasm at all times of day, and mutant TIM
      attenuates transcriptional feedback by PER in cultured cells, suggesting that it
      holds PER in the cytoplasm. In fact, much of the reduced phosphorylation of PER
      in the new tim mutant appears to result from the cytoplasmic localization of PER.
      Interestingly, mutating a threonine near the original mutation produces similar
      phenotypes, raising the possibility that defective phosphorylation is the basis
      of TIM dysfunction in the novel tim mutant. We also show that a stable form of
      PER is cytoplasmic in tim-null flies. These studies establish an essential role
      of TIM in the timed nuclear entry of PER.

PMID- 21734290
TI  - Dynamic cyclovergence during vertical translation in humans.
AB  - When humans are accelerated along the body vertical, the right and left eyes show
      oppositely directed torsional modulation (cyclovergence). The origin of this
      paradoxical response is unknown. We studied cyclovergence during linear
      sinusoidal vertical motion in healthy humans. A small head-fixed visual target
      minimized horizontal and vertical motion of the eyes and therefore isolated the
      torsional component. For stimuli between 1 and 2 Hz (near the natural range of
      head motion), the phase of cyclovergence with respect to inertial acceleration
      was 8.7 +/- 2.4 degrees  (mean +/- 95% CI) and the sensitivity (in degrees per
      second per g) showed a small but statistically significant increase with
      frequency. These characteristics contrast with those of cycloversion (conjugate
      torsion) during horizontal (interaural) inertial stimuli at similar frequencies.
      From these and previous results, we propose that cyclovergence during vertical
      translation has two sources, one, like cycloversion, from the low-frequency
      component of linear acceleration, and another, which we term dynamic
      cyclovergence, with high-pass characteristics. Furthermore, we suggest that this
      cyclovergence response in humans is a vestige of the response of lateral-eyed
      animals to vertical linear acceleration of the head.

PMID- 21734291
TI  - The role of neuronal connexins 36 and 45 in shaping spontaneous firing patterns
      in the developing retina.
AB  - Gap junction coupling synchronizes activity among neurons in adult neural
      circuits, but its role in coordinating activity during development is less known.
      The developing retina exhibits retinal waves--spontaneous depolarizations that
      propagate among retinal interneurons and drive retinal ganglion cells (RGCs) to
      fire correlated bursts of action potentials. During development, two connexin
      isoforms, connexin 36 (Cx36) and Cx45, are expressed in bipolar cells and RGCs,
      and therefore provide a potential substrate for coordinating network activity. To
      determine whether gap junctions contribute to retinal waves, we compared
      spontaneous activity patterns using calcium imaging, whole-cell recording, and
      multielectrode array recording in control, single-knock-out (ko) mice lacking
      Cx45 and double-knock-out (dko) mice lacking both isoforms. Wave frequency,
      propagation speed, and bias in propagation direction were similar in control,
      Cx36ko, Cx45ko, and Cx36/45dko retinas. However, the spontaneous firing rate of
      individual retinal ganglion cells was elevated in Cx45ko retinas, similar to
      Cx36ko retinas (Hansen et al., 2005; Torborg and Feller, 2005), a phenotype that
      was more pronounced in Cx36/45dko retinas. As a result, spatial correlations, as
      assayed by nearest-neighbor correlation and functional connectivity maps, were
      significantly altered. In addition, Cx36/45dko mice had reduced eye-specific
      segregation of retinogeniculate afferents. Together, these findings suggest that
      although Cx36 and Cx45 do not play a role in gross spatial and temporal
      propagation properties of retinal waves, they strongly modulate the firing
      pattern of individual RGCs, ensuring strongly correlated firing between nearby
      RGCs and normal patterning of retinogeniculate projections.

PMID- 21734292
TI  - Neto1 is an auxiliary subunit of native synaptic kainate receptors.
AB  - Ionotropic glutamate receptors of AMPA, NMDA, and kainate receptor (KAR) subtypes
      mediate fast excitatory synaptic transmission in the vertebrate CNS. Auxiliary
      proteins have been identified for AMPA and NMDA receptor complexes, but little is
      known about KAR complex proteins. We previously identified the CUB (complement
      C1r/C1s, Uegf, Bmpl) domain protein, Neto1, as an NMDA receptor-associated
      polypeptide. Here, we show that Neto1 is also an auxiliary subunit for endogenous
      synaptic KARs. We found that Neto1 and KARs coimmunoprecipitated from brain
      lysates, from postsynaptic densities (PSDs) and, in a manner dependent on Neto1
      CUB domains, when coexpressed in heterologous cells. In Neto1-null mice, there
      was an ~50% reduction in the abundance of GluK2-KARs in hippocampal PSDs. Neto1
      strongly localized to CA3 stratum lucidum, and loss of Neto1 resulted in a
      selective deficit in KAR-mediated neurotransmission at mossy fiber-CA3 pyramidal
      cell (MF-CA3) synapses: KAR-mediated EPSCs in Neto1-null mice were reduced in
      amplitude and decayed more rapidly than did those in wild-type mice. In contrast,
      the loss of Neto2, which also localizes to stratum lucidum and interacts with
      KARs, had no effect on KAR synaptic abundance or MF-CA3 transmission. Indeed, MF
      CA3 KAR deficits in Neto1/Neto2-double-null mutant mice were indistinguishable
      from Neto1 single-null mice. Thus, our findings establish Neto1 as an auxiliary
      protein required for synaptic function of KARs. The ability of Neto1 to regulate
      both NMDARs and KARs reveals a unique dual role in controlling synaptic
      transmission by serving as an auxiliary protein for these two classes of
      ionotropic glutamate receptors in a synapse-specific fashion.

PMID- 21734293
TI  - Predicting future sensorimotor states influences current temporal decision
      making.
AB  - Accurate motor execution is achieved by estimating future sensory states via a
      forward model of limb dynamics. In the current experiment, we probed the time
      course over which state estimation evolves during movement planning by combining
      a bimanual arm crossing movement with a temporal order judgment (TOJ) task. Human
      participants judged which of two successive vibrotactile stimuli delivered to
      each index finger arrived first as they were preparing to either cross or uncross
      their hands. TOJ error rate was found to systematically vary in a time- and
      direction-dependent manner. When planning to cross the hands, error rate
      systematically increased as the vibrotactile stimuli were delivered closer in
      time to the onset of the movement. By contrast, planning to uncross the hands led
      to a gradual reduction in error rate as movement planning progressed. In both
      cases, these changes occurred before the actual alteration in hand configuration.
      We suggest that these systematic changes in error represent an interaction
      between the evolving state estimation processes and decisions regarding the
      timing of successive events.

PMID- 21734294
TI  - Neural coding of syntactic structure in learned vocalizations in the songbird.
AB  - Although vocal signals including human languages are composed of a finite number
      of acoustic elements, complex and diverse vocal patterns can be created from
      combinations of these elements, linked together by syntactic rules. To enable
      such syntactic vocal behaviors, neural systems must extract the sequence patterns
      from auditory information and establish syntactic rules to generate motor
      commands for vocal organs. However, the neural basis of syntactic processing of
      learned vocal signals remains largely unknown. Here we report that the basal
      ganglia projecting premotor neurons (HVC(X) neurons) in Bengalese finches
      represent syntactic rules that generate variable song sequences. When vocalizing
      an alternative transition segment between song elements called syllables, sparse
      burst spikes of HVC(X) neurons code the identity of a specific syllable type or a
      specific transition direction among the alternative trajectories. When vocalizing
      a variable repetition sequence of the same syllable, HVC(X) neurons not only
      signal the initiation and termination of the repetition sequence but also
      indicate the progress and state-of-completeness of the repetition. These
      different types of syntactic information are frequently integrated within the
      activity of single HVC(X) neurons, suggesting that syntactic attributes of the
      individual neurons are not programmed as a basic cellular subtype in advance but
      acquired in the course of vocal learning and maturation. Furthermore, some
      auditory-vocal mirroring type HVC(X) neurons display transition selectivity in
      the auditory phase, much as they do in the vocal phase, suggesting that these
      songbirds may extract syntactic rules from auditory experience and apply them to
      form their own vocal behaviors.

PMID- 21734295
TI  - Presynaptic control of rapid estrogen fluctuations in the songbird auditory
      forebrain.
AB  - Within the CNS of vertebrates, estrogens can directly modulate neural circuits
      that govern a wide range of behaviors, including feeding, spatial navigation,
      reproduction, and auditory processing. The rapid actions of estrogens in brain
      (seconds to minutes) have become well established, but it is unclear how
      estrogens are synthesized and released within restricted temporal and spatial
      domains in neural circuits. Anatomical localization of the estrogen synthesis
      enzyme (aromatase) within presynaptic terminals suggests that neuroestrogens can
      be synthesized directly at the neuronal synapse. A consequent prediction follows
      that synaptic estrogen production is controlled via classical electrochemical
      events in neurons. Here, we present evidence that acute fluctuations in local
      neuroestrogen levels in the forebrain of the zebra finch depend on calcium influx
      within presynaptic terminals. In vivo experiments using microdialysis linked to a
      sensitive estrogen ELISA showed that local forebrain neuroestrogens were both
      suppressed by potassium-evoked excitation and upregulated during 30 min periods
      of extracellular calcium depletion in a region enriched with presynaptic
      aromatase. Furthermore, potassium-evoked changes in local neuroestrogens were
      blocked by targeted delivery of the voltage-gated calcium channel blocker omega
      conotoxin GVIA. Together, these experiments indicate that neuroestrogens are
      controlled by specific, depolarization-sensitive, calcium-dependent events within
      forebrain presynaptic terminals.

PMID- 21734296
TI  - Optimal and suboptimal use of postsaccadic vision in sequences of saccades.
AB  - Saccades are imprecise, due to sensory and motor noise. To avoid an accumulation
      of errors during sequences of saccades, a prediction derived from the efference
      copy can be combined with the reafferent visual feedback to adjust the following
      eye movement. By varying the information quantity of the visual feedback, we
      investigated how the reliability of the visual information affects the
      postsaccadic update in humans. Two elements of the visual scene were manipulated,
      the saccade target or the background, presented either together or in isolation.
      We determined the weight of the postsaccadic visual information by measuring the
      effect of intrasaccadic visual shifts on the following saccade. We confirmed that
      the weight of visual information evolves with information quantity as predicted
      for a statistically optimal system. In particular, we found that the visual
      background alone can guide the postsaccadic update, and that information from
      target and background are optimally combined. Moreover, these visual weights are
      adjusted dynamically and on a trial-to-trial basis to the level of visual noise
      determined by target eccentricity and reaction time. In contrast, we uncovered a
      dissociation between the visual signals used to update the next planned saccade
      (main saccade) and those used to generate an involuntary corrective saccade. The
      latter was exclusively based on visual information about the target, and
      discarded all information about the background: a suboptimal use of visual
      evidence.

PMID- 21734297
TI  - How each movement changes the next: an experimental and theoretical study of fast
      adaptive priors in reaching.
AB  - Most voluntary actions rely on neural circuits that map sensory cues onto
      appropriate motor responses. One might expect that for everyday movements, like
      reaching, this mapping would remain stable over time, at least in the absence of
      error feedback. Here we describe a simple and novel psychophysical phenomenon in
      which recent experience shapes the statistical properties of reaching,
      independent of any movement errors. Specifically, when recent movements are made
      to targets near a particular location subsequent movements to that location
      become less variable, but at the cost of increased bias for reaches to other
      targets. This process exhibits the variance-bias tradeoff that is a hallmark of
      Bayesian estimation. We provide evidence that this process reflects a fast, trial
      by-trial learning of the prior distribution of targets. We also show that these
      results may reflect an emergent property of associative learning in neural
      circuits. We demonstrate that adding Hebbian (associative) learning to a model
      network for reach planning leads to a continuous modification of network
      connections that biases network dynamics toward activity patterns associated with
      recent inputs. This learning process quantitatively captures the key results of
      our experimental data in human subjects, including the effect that recent
      experience has on the variance-bias tradeoff. This network also provides a good
      approximation of a normative Bayesian estimator. These observations illustrate
      how associative learning can incorporate recent experience into ongoing
      computations in a statistically principled way.

PMID- 21734298
TI  - A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP
      melastatin 1 channel to retinal depolarizing bipolar cell dendrites.
AB  - Expression of channels to specific neuronal sites can critically impact their
      function and regulation. Currently, the molecular mechanisms underlying this
      targeting and intracellular trafficking of transient receptor potential (TRP)
      channels remain poorly understood, and identifying proteins involved in these
      processes will provide insight into underlying mechanisms. Vision is dependent on
      the normal function of retinal depolarizing bipolar cells (DBCs), which couple a
      metabotropic glutamate receptor 6 to the TRP melastatin 1 (TRPM1) channel to
      transmit signals from photoreceptors. We report that the extracellular membrane
      attached protein nyctalopin is required for the normal expression of TRPM1 on the
      dendrites of DBCs in mus musculus. Biochemical and genetic data indicate that
      nyctalopin and TRPM1 interact directly, suggesting that nyctalopin is acting as
      an accessory TRP channel subunit critical for proper channel localization to the
      synapse.

PMID- 21734299
TI  - Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the
      nucleus accumbens.
AB  - Caffeine, the most widely used psychoactive compound, is an adenosine receptor
      antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors
      (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to
      produce arousal have not been identified. Using selective gene deletion
      strategies based on the Cre/loxP technology in mice and focal RNA interference to
      silence the expression of A(2A)Rs in rats by local infection with adeno
      associated virus carrying short-hairpin RNA, we report that the A(2A)Rs in the
      shell region of the nucleus accumbens (NAc) are responsible for the effect of
      caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when
      A(2A)Rs were focally removed from the NAc core or other A(2A)R-positive areas of
      the basal ganglia. Our observations suggest that caffeine promotes arousal by
      activating pathways that traditionally have been associated with motivational and
      motor responses in the brain.

PMID- 21734300
TI  - alpha-Syn suppression reverses synaptic and memory defects in a mouse model of
      dementia with Lewy bodies.
AB  - Abnormally accumulated alpha-synuclein (alpha-syn) is a pathological hallmark of
      Lewy body-related disorders such as Parkinson's disease (PD) and dementia with
      Lewy body disease (DLB). However, it is not well understood whether and how
      abnormal accumulation of alpha-syn leads to cognitive impairment or dementia in
      PD and DLB. Furthermore, it is not known whether targeted removal of alpha-syn
      pathology can reverse cognitive decline. Here, we found that the distribution of
      alpha-syn pathology in an inducible alpha-syn transgenic mouse model
      recapitulates that in human DLB. Abnormal accumulation of alpha-syn in the limbic
      system, particularly in the hippocampus, correlated with memory impairment and
      led to structural synaptic deficits. Furthermore, when alpha-syn expression was
      suppressed, we observed partial clearing of pre-existing alpha-syn pathology and
      reversal of structural synaptic defects, resulting in an improvement in memory
      function.

PMID- 21734301
TI  - Requirement for DNA ligase IV during embryonic neuronal development.
AB  - The embryonic ventricular and subventricular zones (VZ/SVZ) contain the neuronal
      stem and progenitor cells and undergo rapid proliferation. The intermediate zone
      (IZ) contains nonreplicating, differentiated cells. The VZ/SVZ is hypersensitive
      to radiation-induced apoptosis. Ablation of DNA non-homologous end-joining (NHEJ)
      proteins, XRCC4 or DNA ligase IV (LigIV), confers ataxia telangiectasia mutated
      (ATM)-dependent apoptosis predominantly in the IZ. We examine the mechanistic
      basis underlying these distinct sensitivities using a viable LigIV (Lig4(Y288C))
      mouse, which permits an examination of the DNA damage responses in the embryonic
      and adult brain. Via combined analysis of DNA breakage, apoptosis, and cell-cycle
      checkpoint control in tissues, we show that apoptosis in the VZ/SVZ and IZ is
      activated by low numbers of DNA double-strand breaks (DSBs). Unexpectedly, high
      sensitivity in the VZ/SVZ arises from sensitive activation of ATM-dependent
      apoptosis plus an ATM-independent process. In contrast, the IZ appears to be
      hypersensitive to persistent DSBs. NHEJ functions efficiently in both
      compartments. The VZ/SVZ and IZ regions incur high endogenous DNA breakage, which
      correlates with VZ proliferation. We demonstrate a functional G(2)/M checkpoint
      in VZ/SVZ cells and show that it is not activated by low numbers of DSBs,
      allowing damaged VZ/SVZ cells to transit into the IZ. We propose a novel model in
      which microcephaly in LIG4 syndrome arises from sensitive apoptotic induction
      from persisting DSBs in the IZ, which arise from high endogenous breakage in the
      VZ/SVZ and transit of damaged cells to the IZ. The VZ/SVZ, in contrast, is highly
      sensitive to acute radiation-induced DSB formation.

PMID- 21734302
TI  - Molecular microdomains in a sensory terminal, the vestibular calyx ending.
AB  - Many primary vestibular afferents form large cup-shaped postsynaptic terminals
      (calyces) that envelope the basolateral surfaces of type I hair cells. The
      calyceal terminals both respond to glutamate released from ribbon synapses in the
      type I cells and initiate spikes that propagate to the afferent's central
      terminals in the brainstem. The combination of synaptic and spike initiation
      functions in these unique sensory endings distinguishes them from the axonal
      nodes of central neurons and peripheral nerves, such as the sciatic nerve, which
      have provided most of our information about nodal specializations. We show that
      rat vestibular calyces express an unusual mix of voltage-gated Na and K channels
      and scaffolding, cell adhesion, and extracellular matrix proteins, which may hold
      the ion channels in place. Protein expression patterns form several microdomains
      within the calyx membrane: a synaptic domain facing the hair cell, the heminode
      abutting the first myelinated internode, and one or two intermediate domains.
      Differences in the expression and localization of proteins between afferent types
      and zones may contribute to known variations in afferent physiology.

PMID- 21734303
TI  - Distinct functional domains contribute to degradation of the low density
      lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible Degrader of the
      LDLR (IDOL).
AB  - We recently identified the liver X receptor-regulated E3 ubiquitin ligase
      inducible degrader of the LDL receptor (IDOL) as a modulator of lipoprotein
      metabolism. Acting as an E3 ubiquitin ligase, IDOL triggers ubiquitination and
      subsequent degradation of the low density lipoprotein receptor (LDLR). We
      demonstrate here that this outcome requires the conserved FERM and RING domains
      present in IDOL. The RING domain promotes ubiquitination in vitro and Lys-63
      specific ubiquitination of the LDLR in vivo in response to IDOL or liver X
      receptor activation. We further identify RING residues that differentially
      influence ubiquitination of the LDLR or stability of IDOL. The FERM domain
      interacts with the LDLR and in living cells co-localizes with the receptor at the
      plasma membrane. Homology modeling revealed a phosphotyrosine-binding element
      embedded in the FERM domain. Mutating residues within this region or residues in
      the LDLR preceding the NPVY endocytosis motif abrogate LDLR degradation by IDOL.
      Collectively, our results indicate that both the FERM and RING domains are
      required for promoting lysosomal degradation of the LDLR by IDOL. Our findings
      may facilitate development of structure-based IDOL inhibitors aimed at increasing
      LDLR abundance in therapeutic strategies to treat cardiovascular disease.

PMID- 21734304
TI  - Opportunities for extracurricular physical activity in North Carolina middle
      schools.
AB  - BACKGROUND: This study's purpose was to assess the opportunities for North
      Carolina adolescents to be physically active in extracurricular middle school
      environments and to compare opportunities across community types. METHODS: Data
      were analyzed based on the results of an electronic questionnaire distributed to
      a sample of 431 schools with a response rate of 75.4% (N = 325). RESULTS: Nearly
      all schools offered interscholastic sports while fewer than half offered
      intramurals or noncompetitive activities to students. "Open gym" was offered at
      only 35% of schools, while 24% of schools offered extracurricular activities to
      students with disabilities. Overall, 43.4% of schools offered special
      transportation to students who participated in some extracurricular physical
      activities. Schools in rural areas generally offered fewer programs and had fewer
      supports than schools located in more urbanized areas. Over two-thirds of rural
      schools offered no extracurricular programs other than interscholastic sports.
      CONCLUSIONS: Schools can be important settings for physical activity. North
      Carolina's middle schools and its rural schools in particular, are falling short
      in efforts to provide extracurricular physical activity programming recommended
      by researchers and policy groups. Lower accessibility to extracurricular physical
      activities may partially contribute to higher levels of physical inactivity found
      in the state.

PMID- 21734305
TI  - Prevalence and social-environmental correlates of sports team participation among
      alternative high school students.
AB  - BACKGROUND: Alternative high school (AHS) students have low levels of physical
      activity (PA) and high rates of overweight/obesity. Sports team participation, a
      specific form of PA, is associated with increased PA and decreased
      overweight/obesity in general adolescent populations. However, little is known
      about the prevalence and correlates of sports team participation among AHS
      students. METHODS: In 2006, students (n = 145; mean age = 17 years; 52% male; 61%
      minorities; 64% low-income) attending 6 AHS in Minneapolis/St. Paul completed
      self-administered surveys. Mixed model logistic regression was used to examine
      cross-sectional associations between sports team participation and school staff
      support for PA, friend support for PA, and perceived barriers to PA. RESULTS:
      Among students, 40% participated on >= 1 sports teams. Odds of participating on a
      sports team were positively associated with support for PA from school staff (OR
      = 1.12, P = .014) and friends (OR = 1.15, P = .005), but inversely associated
      with perceived barriers to PA (OR = 0.95, P = .014). CONCLUSION: Results suggest
      that efforts to increase sports team participation among AHS students should
      target social-environmental factors. Further study is warranted.

PMID- 21734306
TI  - Individual, social, and physical environment factors associated with electronic
      media use among children: sedentary behavior at home.
AB  - BACKGROUND: Individual, home social and physical environment correlates of
      electronic media (EM) use among children were examined and pattern of differences
      on school and weekend days. METHODS: Youth (n = 298) aged 11 to 12 years self
      reported time spent using EM (TV, video/DVD, computer use, and electronic games)
      on a typical school and a weekend day, each dichotomized at the median to
      indicate heavy and light EM users. Anthropometric measurements were taken.
      Logistic regression examined correlates of EM use. RESULTS: In total, 87% of
      participants exceeded electronic media use recommendations of <= 2 hrs/day.
      Watching TV during breakfast (OR = 3.17) and after school (OR = 2.07), watching
      TV with mother (OR = 1.96), no rule(s) limiting time for computer game usage (OR
      = 2.30), having multiple (OR = 2.99) EM devices in the bedroom and BMI (OR =
      1.15) were associated with higher odds of being heavy EM user on a school day.
      Boys (OR = 2.35) and participants who usually watched TV at midday (OR = 2.91)
      and late at night (OR = 2.04) had higher odds of being a heavy EM user on the
      weekend. CONCLUSIONS: Efforts to modify children's EM use should focus on a mix
      of intervention strategies that address patterns and reinforcement of TV viewing,
      household rules limiting screen time, and the presence of EM devices in the
      child's bedroom.

PMID- 21734307
TI  - Social cognitive correlates of physical activity: findings from a cross-sectional
      study of adults with relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Persons with multiple sclerosis (MS) are often physically inactive
      and sedentary. This observation has prompted the search for modifiable variables
      derived from established theories that act as correlates of physical activity.
      Such variables would presumably represent targets for interventions designed to
      promote change in physical activity behavior among persons with MS. The current
      study examined social cognitive variables as correlates of physical activity in
      persons with MS. METHODS: Persons (N = 218) with relapsing-remitting MS completed
      a questionnaire battery that assessed physical activity behavior; self-efficacy
      for physical activity; physical, social, and self-evaluative outcome expectations
      for exercise, functional limitations as an impediment for physical activity, and
      exercise goal-setting. The battery was delivered and returned through the US
      postal service. Data were analyzed using covariance modeling in Mplus 3.0.
      RESULTS: Self-efficacy had indirect effects on physical activity via impediments
      (path coefficient = .10, P < .005), self-evaluative outcome expectations (path
      coefficient = .07, P < .025), and goal-setting (path coefficient = .09, P < .01).
      The model explained 40% of variance in self-reported physical activity.
      CONCLUSIONS: This cross-sectional study suggests that self-efficacy is indirectly
      associated with physical activity by way of goals, self-evaluative outcome
      expectations, and impediments in persons with relapsing-remitting MS.

PMID- 21734308
TI  - Environmental determinants of children's physical activity in residential
      children's homes.
AB  - BACKGROUND: Children in residential children's homes (RCH) may be at increased
      risk for physical inactivity due to decreased access to opportunities for
      activity. Little is known about environmental determinants of physical activity
      for children in RCH. METHODS: Thirty-minute blocks of MVPA and Total METs were
      measured using the 3-Day Physical Activity Recall (3DPAR). A staff interview,
      based on the Structural Ecologic Model of Health Behavior, assessed physical
      activity opportunities, structures, characteristics, policies, and social
      environment. Wilcoxon 2-sample tests were used to examine differences in
      environment by location and presence of a recreation director. Mixed model ANOVAs
      assessed the differences in child level activity by environmental variables.
      RESULTS: There were significant correlations between opportunities and
      characteristics of physical activity, facilities, and equipment with total METS
      for children. Children in homes with a recreation director and homes in rural
      locations reported more physical activity. Only rural location had a significant
      effect on physical activity. Presence of a recreation director was significant in
      several models. CONCLUSIONS: Rural location may be conducive for increased
      physical activity in children at RCH. Employing a recreation director or other
      trained personnel may be an important policy determinant of physical activity for
      children.

PMID- 21734309
TI  - An exploration of children's perceptions and enjoyment of school-based physical
      activity and physical education.
AB  - BACKGROUND: The promotion of physical activity among young children has become a
      universal challenge. Children spend large amounts of time in school, making it an
      attractive setting in which to promote positive health behaviors. The purpose of
      this study was to investigate school-based physical activity behavior and its
      determinants in young Irish children. METHODS: Participants self-reported school
      based free-play activity, commuting to school behavior, and levels of enjoyment
      of physical education and physical activity. RESULTS: Data were collected from
      605 children, mean age was 8.8 years (+/-2.2; range 5-14 years), 44% were female.
      Thirty-nine percent of children actively commuted to school, with 40% of males
      compared with 34.8% of females walking to school. Boys reported more physically
      active free-play activity (88.6% at break and 90.9% at lunch time) compared with
      girls (70.8% and 83.7% respectively). Physical education was a top 3 favorite
      subject for 78% of children and 50.7% reported they would prefer to take part in
      more active pastimes directly after school. CONCLUSIONS: Strategies for
      increasing active commuting are required. Boys and girls are more alike than
      unlike in their behaviors and attitudes. Teachers should capitalize on the fact
      that children's favorite subject is physical education to promote physical
      activity.

PMID- 21734310
TI  - Leisure-time physical activity during pregnancy and offspring size at 18 to 24
      months.
AB  - BACKGROUND: Leisure-time physical activity (LTPA) during pregnancy has maternal
      benefits, but effects on offspring have not often been considered. This study
      aimed to determine associations among trimester-specific LTPA during pregnancy
      and toddler size. METHODS: Women (n = 300) were recruited while pregnant in 2006.
      At follow-up (2008), women reported demographics; recalled type, duration, and
      frequency of trimester-specific LTPA (MET.min/wk); and rated their toddler's
      current LTPA level (more, same, or less than others their age). A subset (n = 23)
      volunteered to have maternal and toddler height, weight, and body fat measured.
      Maternal body mass index (BMI) and toddler weight-for-height z-scores (WHZ) were
      calculated. RESULTS: Median toddler WHZ was 0.6 (range -0.5 to 2.9). In Spearman
      correlations, third trimester LTPA was marginally associated with lower toddler
      weight (rs = -0.39, P = .06) and WHZ (rs = -0.40, P = .06), but no other measures
      of maternal LTPA and toddler body size were related. Birth weight z-score was
      positively associated with toddler weight (rs = 0.51, P = .01) but negatively
      associated with percent body fat (rs= -0.46, P = .03). Measures of maternal size
      were unassociated with toddler size. CONCLUSIONS: These results provide
      preliminary support for LTPA during late pregnancy to have a lasting effect on
      offspring size.

PMID- 21734311
TI  - UNISTEP (university students exercise and physical activity) study: a pilot study
      of the effects of accumulating 10,000 steps on health and fitness among
      university students.
AB  - BACKGROUND: Recent public health initiatives have promoted accumulating 10,000
      steps per day. Little previous research has evaluated its effects in young
      adults. The aim of this study was to determine the effects of taking 10,000 steps
      per day on fitness and cardiovascular risk factors in sedentary university
      students. METHODS: Healthy, sedentary students (mean age 21.16 +/- SD 6.17) were
      randomly allocated to take 10,000 steps per day or to a control group who
      maintained their habitual activity. Members of the 10,000 step group wore a
      pedometer and reported daily step count in a diary. Outcome measurements (20
      meter multistage shuttle run, BMI, and blood pressure) were measured before and
      after 6 weeks. RESULTS: There were no significant differences between the groups
      at baseline. After 6 weeks, the 10,000 steps group were taking significantly more
      steps (8824.1 +/- SD 5379.3 vs. 12635.9 +/- SD 6851.3; P = .03).No changes were
      observed in fitness, or BMI (P > .05). Significant reductions in blood pressure
      (P = .04) in the 10,000 step group. CONCLUSIONS: A daily target of 10,000 steps
      may be an appropriate intervention in sedentary university students to increase
      their physical activity levels. The positive health benefits of simple everyday
      physical activity should be promoted among health professionals.

PMID- 21734312
TI  - Accelerometer test-retest reliability by data processing algorithms: results from
      the Twin Cities Walking Study.
AB  - BACKGROUND: The purpose of this study was to determine 1) the test-retest
      reliability of adult accelerometer-measured physical activity, and 2) how data
      processing decisions affect physical activity levels and test-retest reliability.
      METHODS: 143 people wore the ActiGraph accelerometer for 2 7-day periods, 1 to 4
      weeks apart. Five algorithms, varying nonwear criteria (20 vs. 60 min of 0
      counts) and minimum wear requirements (6 vs. 10 hrs/day for >= 4 days) and a
      separate algorithm requiring >= 3 counts per min and >= 2 hours per day, were
      used to process the accelerometer data. RESULTS: Processing the accelerometer
      data with different algorithms resulted in different levels of counts per day,
      sedentary, and moderate-to-vigorous physical activity. Reliability correlations
      were very good to excellent (ICC = 0.70-0.90) for almost all algorithms and there
      were no significant differences between physical activity measures at Time 1 and
      Time 2. CONCLUSIONS: This paper presents the first assessment of test-retest
      reliability of the Actigraph over separate administrations in free-living
      subjects. The ActiGraph was highly reliable in measuring activity over a 7-day
      period in natural settings but data were sensitive to the algorithms used to
      process them.

PMID- 21734313
TI  - Activity counts from accelerometers do not add value to energy expenditure
      predictions in sedentary overweight individuals during weight loss interventions.
AB  - BACKGROUND: Knowing the total energy expenditure (TEE) of overweight adults is
      important for prescribing weight loss interventions. However, objective
      measurements of TEE may not always be readily available and can be expensive.
      This study aimed to investigate the validity of RT3 accelerometers in predicting
      the TEE of sedentary overweight adults, and to identify any sensitivity to
      anthropometric changes. METHODS: The analysis used data from a 12-week weight
      loss study. At baseline and 12-week, TEE was predicted using RT3 accelerometers
      during whole room calorimeter stays. Bias between 2 methods was compared at and
      between the baseline and 12-week measurement points. Multiple regression analyses
      of TEE data were conducted. RESULTS: Predicted and measured values for TEE were
      not different at baseline (P = .677) but were significantly different after
      weight loss (P = .007). However, the mean bias between methods was small (<100
      kcal/d) and was not significantly different between 2 time-points. RT3 activity
      counts explained an additional 2% of the variation in TEE at 12-week but not at
      baseline. CONCLUSION: RT3 accelerometers are not sensitive to body composition
      changes and do not explain variation in TEE of overweight and obese individuals
      in a sedentary environment.

PMID- 21734314
TI  - Accelerometer response to physical activity intensity in normal-weight versus
      overweight African American children.
AB  - BACKGROUND: Different movement efficiency in overweight children may affect
      accelerometer output data. The purpose was to investigate the ability of
      accelerometers to assess physical activity intensity and number of steps in
      normal-weight compared with overweight children. METHODS: Eleven normal-weight
      and 14 overweight African American children walked at 2, 4, 5, and 6 km/h on a
      treadmill wearing Lifecorder, ActiGraph, RT3, and Biotrainer. Oxygen uptake was
      measured and steps manually counted. Fat free mass (FFM) was assessed from
      bioelectrical impedance analysis. Accelerometer counts and the individual linear
      regression lines of accelerometer counts versus VO(2)/FFM were evaluated,
      together with steps recorded by Lifecorder and Actigraph. RESULTS: Correlations
      between accelerometer counts and VO(2)/FFM for all monitors were r >= .95 (P <
      .01). The accelerometer counts and their relationship to VO(2)/FFM did not
      generally differ significantly by body weight status. Lifecorder and Actigraph
      underestimated steps at 4, 5, and 6 km/h by less than 9%, but the error was up to
      -95% at 2 km/h. CONCLUSIONS: All 4 accelerometers show high ability to assess
      physical activity intensity, and can be used to compare physical activity between
      normal-weight and overweight children. The Lifecorder and the ActiGraph showed
      high accuracy in assessing steps, providing speed of movement exceeded 2 km/h.

PMID- 21734315
TI  - U.S. population profile of time-stamped accelerometer outputs: impact of wear
      time.
AB  - BACKGROUND: We examined the effects of wear time on a population profile of time
      stamped accelerometer outputs using the 2005-2006 National Health and Nutrition
      Examination Survey (NHANES) data representing 3744 adults >= 20 years of age.
      METHODS: Outputs included activity counts, steps, and time variables: nonwear
      (macro-determined), sedentary behavior (<100 activity counts/minute), and time in
      low (100-499 activity counts/minute), light (500-2019 activity counts/minute),
      and moderate-to-vigorous physical activity (MVPA; >=2020 activity counts/minute)
      intensities. We describe mean values according to a 24-hour clock. Analysis was
      repeated in a reduced data set with only those who wore the accelerometer for 60
      minutes within each considered hour of the day. RESULTS: Between 12:00 and 17:00,
      U.S. adults spend approximately 31 minutes each hour in sedentary behaviors, and
      approximately 14 minutes, 10 minutes, and 2 minutes in low, light, and MVPA
      intensity activity, respectively. Removing the effect of nonwear time, sedentary
      behaviors are reduced in the morning hours and increase in the evening hours.
      CONCLUSION: At either end of the day, nonwear time appears to distort population
      estimates of all accelerometer time and physical activity volume indicators, but
      its effects are particularly clear on population estimates of time spent in
      sedentary behavior.

PMID- 21734316
TI  - Adherence to accelerometer protocols among women from economically disadvantaged
      neighborhoods.
AB  - BACKGROUND: Objective measurement of physical activity with accelerometers is a
      challenging task in community-based intervention research. Challenges include
      distribution of and orientation to monitors, nonwear, incorrect placement, and
      loss of equipment. Data collection among participants from disadvantaged
      populations may be further hindered by factors such as transportation challenges,
      competing responsibilities, and cultural considerations. METHODS: Research staff
      distributed accelerometers and provided an orientation that was tailored to the
      population group. General adherence strategies such as follow-up calls, daily
      diaries, verbal and written instructions, and incentives were accompanied by
      population-specific strategies such as assisting with transportation, reducing
      obstacles to wearing the accelerometer, tailoring the message to the participant
      population, and creating a nonjudgmental environment. RESULTS: Sixty women asked
      to wear the Actigraph GT1M returned the accelerometer, and 57 of them provided
      sufficient data for analysis (at least 10 hours a day for a minimum of 4 days)
      resulting in 95% adherence to the protocol. Participants wore the accelerometers
      for an average of 5.98 days and 13.15 hours per day. CONCLUSIONS: The high
      accelerometer monitoring adherence among this group of economically disadvantaged
      women demonstrates that collection of high-quality, objective physical activity
      data from disadvantaged populations in field-based research is possible.

PMID- 21734317
TI  - Availability of commercial physical activity facilities and physical activity
      outside of school among high school students.
AB  - BACKGROUND: Environmental factors may play an important role in the determination
      of physical activity behaviors. METHODS: This study used the Child Development
      Supplement of the Panel Study of Income Dynamics to examine the association
      between the availability of objectively measured commercial physical activity
      related instruction facilities and weekly physical activity participation among
      high school students outside of school physical education classes. A Negative
      Binomial count model was used to examine the number of days of vigorous physical
      activity (at least 30 minutes/day) per week and a Probit model was used to
      examine the probability of frequent (4 or more days/week) vigorous physical
      activity participation. RESULTS: The results indicated that an additional
      instruction school per 10,000 capita per 10 square miles was associated with an 8
      percent increase in the weekly number of days of vigorous physical activity
      participation and a 4 percentage point increase in the likelihood of frequent
      physical activity participation for female adolescents only. By income,
      associations were larger for low- versus high-income female youths. CONCLUSION:
      Increased availability of local area physical activity-related instruction
      facilities may help to increase female high school students' physical activity
      levels, particularly among low-income female students.

PMID- 21734318
TI  - Examining indirect associations between physical activity, function, and
      disability in independent- and assisted-living residents.
AB  - BACKGROUND: Few studies have examined physical activity behavior and its
      associated outcomes in older adults living in retirement communities. Guided by
      the disablement model and social cognitive theory, we tested a cross-sectional
      model in which physical activity was hypothesized to influence disability
      indirectly through self-efficacy, functional performance, and functional
      limitations. METHODS: One hundred six older men and women residing in independent
      living (ILF) assisted-living (ALF) facilities completed self-report measures of
      self-efficacy, function, and disability. Objective assessments of physical
      activity and functional performance were conducted using waist-mounted
      accelerometers and the short physical performance battery (SPPB), respectively.
      Path analysis was used to examine the proposed associations among constructs.
      RESULTS: Older adults who were more active were also more efficacious and had
      better physical function and fewer functional limitations. Only higher levels of
      self-efficacy were associated with less disability. The effects of individual
      level covariates were also examined. CONCLUSIONS: This cross-sectional study is
      among the first to examine the associations between physical activity, function,
      and disability among older adults residing in ILFs and ALFs. Future research
      addressing the physical and psychological needs of this growing population is
      warranted.

PMID- 21734319
TI  - Active video games for youth: a systematic review.
AB  - BACKGROUND: A population level increase in physical activity (PA) is critical to
      reduce obesity in youth. Video games are highly popular and active video games
      (AVGs) have the potential to play a role in promoting youth PA. METHOD: Studies
      on AVG play energy expenditure (EE) and maintenance of play in youth were
      systematically identified in the published literature and assessed for quality
      and informational value. RESULTS: Nine studies measuring AVG play EE were
      identified. The meta-analytic estimates of average METs across these studies were
      3.1 (95% CI: 2.6, 3.6) to 3.2 (95% CI: 2.7, 3.7). No games elicited an average EE
      above the 6 MET threshold for vigorous EE. Observed differences between studies
      were likely due to the different types of games used, rather than age or gender.
      Four studies related to maintenance of play were identified. Most studies
      reported AVG use declined over time. Studies were of low-to-medium quality.
      CONCLUSION: AVGs are capable of generating EE in youth to attain PA guidelines.
      Few studies have assessed sustainability of AVG play, which appears to diminish
      after a short period of time for most players. Better-quality future research
      must address how AVG play could be maintained over longer periods of time.

PMID- 21734320
TI  - [Biological consequences of oxidative stress induced by pesticides].
AB  - Pesticides are used to protect plants and numerous plant products. They are also
      utilized in several industrial branches. These compounds are highly toxic to
      living organisms. In spite of close supervision in the use of pesticides there is
      a serious risk that these agents are able to spread into the environment and
      contaminate water, soil, food, and feedstuffs. Recently, more and more studies
      have been focused on understanding the toxic mechanisms of pesticide actions. The
      data indicate that the toxic action of pesticides may include the induction of
      oxidative stress and accumulation of free radicals in the cell. Long-lasting or
      acute oxidative stress disturbs cell metabolism and is able to produce permanent
      changes in the structure of proteins, lipids, and DNA. The proteins that are
      oxidized may lose or enhance their activity. Moreover, the proteins oxidized are
      able to form aggregates that inhibit the systems responsible for protein
      degradation and lead to alterations of proteins in the cell. Once oxidized,
      lipids have the capacity to damage and depolarize cytoplasmic membranes. Free
      oxygen radicals are harmful to DNA including damage to single nitric bases, DNA
      strand breaks and adduct production. Many studies indicate that oxidative stress
      may accelerate development of numerous diseases including cancer and
      neurodegenerative ones such as Alzheimer's and Parkinson's disease and may also
      be responsible for infertility.

PMID- 21734321
TI  - [Expression systems of cytochrome P450 proteins in studies of drug metabolism in
      vitro].
AB  - Cytochrome P450 proteins are the most important enzymes involved in metabolic
      activation or detoxification of various drugs used in clinical practice. However,
      some drug metabolism pathways may be responsible for their increased toxicity.
      New expression systems of cytochrome P450 proteins in mammalian cells, including
      human, are designed to explore the influence of metabolism on the cellular and
      molecular mechanisms of action of potential drugs and those used therapeutically.
      They can also be used to study the effect of tested compounds on activity and
      expression of metabolizing enzymes. Human tumor cell lines with overexpression of
      cytochrome P450 isoenzymes are of particular importance, especially in studies of
      potential chemotherapeutics. The HepG2 cell line, derived from human liver
      cancer, is the most commonly used in studies on drug metabolism and toxicity.
      However, due to the low level of metabolizing enzymes in these cells, the Hep3A4
      cell line with overexpression of CYP3A4 isoenzyme was developed. The stable
      overexpression of cytochrome P450 isoenzymes was also obtained in other human
      cancer cell lines, including hepatoma HepaRG cells, ovarian cancer IGROV-1 cells,
      colon cancer Caco-2, and LS180 cells. This review describes currently developed
      bacterial, yeast, insect and mammalian (including human) cytochrome P450 protein
      expression systems, in terms of their advantages and disadvantages in the context
      of their suitability for basic research and use on a commercial scale.

PMID- 21734322
TI  - [Engineered spider silk: the intelligent biomaterial of the future. Part I].
AB  - The unique properties of spider silk such as strength, extensibility, toughness,
      biocompatibility and biodegradability are the reasons for the recent development
      in silk biomaterial technology. For a long time scientific progress was impeded
      by limited access to spider silk. However, the development of the molecular
      biology strategy was a breaking point in synthetic spider silk protein design.
      The sequences of engineered spider silk are based on the consensus motives of the
      corresponding natural equivalents. Moreover, the engineered silk proteins may be
      modified in order to gain a new function. The strategy of the hybrid proteins
      constructed on the DNA level combines the sequence of engineered silk, which is
      responsible for the biomaterial structure, with the sequence of polypeptide which
      allows functionalization of the silk biomaterial. The functional domains may
      comprise receptor binding sites, enzymes, metal or sugar binding sites and
      others. Currently, advanced research is being conducted, which on the one hand
      focuses on establishing the particular silk structure and understanding the
      process of silk thread formation in nature. On the other hand, there are attempts
      to improve methods of engineered spider silk protein production. Due to acquired
      knowledge and recent progress in synthetic protein technology, the engineered
      silk will turn into intelligent biomaterial of the future, while its industrial
      production scale will trigger a biotechnological revolution.

PMID- 21734323
TI  - [Engineered spider silk: the intelligent biomaterial of the future. Part II].
AB  - The development and progress in engineered spider silk manufacturing has enabled
      its practical application. Recombinant spider silk can assemble in several
      morphological forms such as films, hydrogels, fibers, scaffolds, microcapsules,
      and micro- and nanospheres. The in vitro fiber formation takes place by mimicking
      the natural spinning process in the spider spinning gland: in the presence of
      phosphate ions and dragging forces. Films are obtained by evaporation of solvent
      from the silk solution, while the result of evaporation of the solvent in the
      presence of porogens is a silk scaffold. Hydrogels are formed by spontaneous
      polymerization of silk particles in solutions at low pH. The silk film assembled
      at the interface of two immiscible phases forms microcapsules. The smallest of
      the described forms--silk spheres--are obtained by salting out the silk protein
      solution after addition of the phosphate ions. Common properties of the silk
      biomaterials are biocompatibility and biodegradability, which make them suitable
      for a number of applications in medicine and pharmacy. Moreover, the strategy of
      hybrid proteins which provides the desired function to biomaterial will further
      expand their potential use.

PMID- 21734324
TI  - [The role of Th1, Th17, and Treg cells in the pathogenesis of rheumatoid
      arthritis including anti-inflammatory action of Th1 cytokines].
AB  - Dysregulation in the immune system plays an important role in the pathogenesis of
      rheumatoid arthritis (RA). The persistent nature of arthritis strengthens the
      suggestion of immune dysfunction, consisting in predominance of the pro
      inflammatory response. It seems that both local and systemic immune
      abnormalities, including PBMC secreting abnormal levels of pro- and anti
      inflammatory cytokines, may be involved in the evolution of the disease. Helper T
      cells (Th) differentiate towards Th1, Th2, Th17, and Treg cells according to the
      cytokine microenvironment. Active RA results from the imbalance in distribution
      of functional pro-inflammatory Th17 and anti-inflammatory Treg cells. Affected
      Th1 cytokine secretion observed in the course of RA contributes to the increase
      in IL-17 production and Th17 infiltration in the synovial tissue. Current studies
      have demonstrated that pro-inflammatory Th1 cytokines may also exert an anti
      inflammatory action on the balance between Th17 and Treg cells by promotion of
      Treg differentiation. In the paper, we also show the influence of TNF-alpha and
      its inhibitors on the distribution of Th subpopulations in RA patients.

PMID- 21734325
TI  - [Peroxisome proliferator-activated receptors (PPAR). Antiproliferative
      properties].
AB  - Peroxisome proliferator-activated receptors (PPAR) are transcription factors that
      belong to the hormone nuclear receptor superfamily. Their main role is control of
      fatty acid metabolism and to maintain glucose homeostasis. Isotype gamma of PPAR
      can also be implicated in proliferation and cellular differentiation of both
      normal and cancer cells. Compounds that are PPARgamma ligands have a negative
      influence on cancer cells and can induce apoptosis, inhibit proliferation or
      induce cellular differentiation of these cells. This review summarizes general
      information about PPAR and focuses on anticancer activities of PPARgamma ligands
      and their use in combined therapy. Combination treatment using PPARgamma ligands
      and other agents, especially retinoids and specific kinase inhibitors, may be an
      effective strategy for chemoprevention and treatment of some cancers.

PMID- 21734326
TI  - [The influence of transcription factors on CD4+ T cell differentiation].
AB  - A number of distinguished populations with manifold functions and various
      pathways of differentiation have been identified within T lymphocytes. The cells
      expressing CD4 coreceptor on their cell surface are the most varied group.
      Depending on changes in different tissue microenvironments induced by such
      cytokines as IL-4, IFN-gamma, IL-10 or TGF-beta, CD4+ T lymphocytes can
      differentiate into alternative subpopulations performing helper,
      regulatory/suppressor function (Th1, Th2, Th9, Th17, Th22, Tfh, iTreg and Tr1).
      In the direction of lineage differentiation of these lymphocytes, transcription
      factors play the key role. The most important of them are T-bet, GATA3,
      RORgammat, FOXP3, AHR and c-Maf. A cytokine binding to a specific receptor
      activates the transcription factors, other DNA-binding proteins, and epigenetic
      alterations, enabling the transcription of proper genetic information. The
      plasticity of CD4+ cell differentiation seems to be in dynamic balance between
      initial commitment and flexibility of these cells in the face of a changing
      environment. Even more, phenotypical and functional borders between particular
      subpopulations have turned out to be fluent. Then, the influence of extrinsic
      factors on the activation of mechanisms responsible for conversion of CD4+ T
      lymphocytes into functional mature cells appears to be more complicated than was
      previously thought.

PMID- 21734327
TI  - [Heat shock proteins in rheumatoid arthritis: friend or foe?].
AB  - Rheumatoid arthritis (RA) is one of the most common rheumatic diseases in the
      world. RA is a progressive and incurable systemic connective tissue disease with
      autoimmune background. Numerous reports indicate that the highly evolutionarily
      conserved heat shock proteins (HSP) are able to interact with the immune system.
      Recent research has shown that HSP play an important role in the regulation of
      chronic inflammation in RA, with the majority of information concerning the role
      of proteins belonging to the HSP70, HSP60 and HSP40 classes. This paper presents
      recent views on the role of HSP in the development of rheumatic diseases, as well
      as the potential for application of HSP in immunotherapy of patients suffering
      from RA.

PMID- 21734328
TI  - [Tumor blood vessels].
AB  - Growth of tumors usually depends on the development of the tumor's own
      vasculature. Small avascular tumors (1-2 mm3) cannot continue growth provided an
      equilibrium between pro-angiogenic and anti-angiogenic factors is maintained
      within the tumor environment. Angiogenesis is not the only factor responsible for
      tumor blood vessels forming, as vasculogenic mimicry plays an equally substantial
      role in this process. Vessel-like structures formed during this process are made
      up from cancer cells, macrophages and mast cells. Certain neoplasms are capable
      of growing without developing their own vasculature; instead they secure growth
      via normal blood vessels of the host. Slowed-down blood flow through an
      abnormally built tumor vascular network is the main reason for cancer cells'
      underoxygenation (hypoxia). Defective blood vessels, with hypoxia resulting, play
      a major role in tumor progression. Underoxygenation induces formation of novel
      vessels and these new defective vessels are in turn the principal reason for
      hypoxia. The latter increases cancer cells' malignancy and invasiveness. A
      particular process, called transdifferentiation, takes place in tumor vasculature
      when hypoxia is present and involves neoplastic cells transforming into
      endothelial cells. Since growth of a tumor is dependent on its own blood supply,
      inhibition of such vascular network growth and/or damage to this network should
      exert a strong impact on tumor growth. Long-term administration of anti
      angiogenic drugs, however, encounters unexpected problems. Anti-angiogenic drug
      resistance, together with paradoxical stimulation of invasiveness and metastasis
      by these drugs, has lately become a dominant issue in anticancer therapy.

PMID- 21734329
TI  - [Thiamine and its derivatives in the regulation of cell metabolism].
AB  - For over 70 years thiamine (vitamin B1) has aroused the interest of biologists,
      biochemists and medical doctors because of its multilateral participation in key
      biochemical and physiological processes. The thiamine molecule is composed of
      pyrimidine and thiazole rings which are linked by a methylene bridge. It is
      synthesized by microorganisms, fungi and plants, whereas animals and humans have
      to obtain it from food. There are several known forms of vitamin B1 inside cells:
      free thiamine, three phosphate esters (mono-, di-, and triphosphate), and the
      recently found adenosine thiamine triphosphate. Thiamine has a dual, coenzymatic
      and non-coenzymatic role. First of all, it is a precursor of thiamin diphosphate,
      which is a coenzyme for over 20 characterized enzymes which are involved in cell
      bioenergetic processes leading to the synthesis of ATP. Moreover, these enzymes
      take part in the biosynthesis of pentose (required for the synthesis of
      nucleotides), amino acids and other organic compounds of cell metabolism. On the
      other hand, recent discoveries show the non-coenzymatic role of thiamine
      derivatives in the process of regulation of gene expression (riboswitches in
      microorganisms and plants), the stress response, and perhaps so far unknown
      signal transduction pathways associated with adverse environmental conditions, or
      transduction of nerve signals with participation of thiamine triphosphate and
      adenosine thiamine triphosphate. From the clinical point of view thiamine
      deficiency is related to beri-beri, Parkinson disease, Alzheimer disease,
      Wernicke-Korsakoff syndrome and other pathologies of the nervous system, and it
      is successfully applied in medical practice. On the other hand, identifying new
      synthetic analogues of thiamine which could be used as cytostatics, herbicides or
      agents preventing deficiency of vitamin B1 is currently the major goal of the
      research. In this paper we present the current state of knowledge of thiamine and
      its derivatives, indicating the participation of these compounds in the
      regulation of cell metabolism at both the coenzymatic and non-coenzymatic level.

PMID- 21734330
TI  - Database supported candidate search for metabolite identification.
AB  - Mass spectrometry is an important analytical technology for the identification of
      metabolites and small compounds by their exact mass. But dozens or hundreds of
      different compounds may have a similar mass or even the same molecule formula.
      Further elucidation requires tandem mass spectrometry, which provides the masses
      of compound fragments, but in silico fragmentation programs require substantial
      computational resources if applied to large numbers of candidate structures. We
      present and evaluate an approach to obtain candidates from a relational database
      which contains 28 million compounds from PubChem. A training phase associates
      tandem-MS peaks with corresponding fragment structures. For the candidate search,
      the peaks in a query spectrum are translated to fragment structures, and the
      candidates are retrieved and sorted by the number of matching fragment
      structures. In the cross validation the evaluation of the relative ranking
      positions (RRP) using different sizes of training sets confirms that a larger
      coverage of training data improves the average RRP from 0.65 to 0.72. Our
      approach allows downstream algorithms to process candidates in order of
      importance.

PMID- 21734331
TI  - Valence band circular dichroism in non-magnetic Ag/Ru(0001) at normal emission.
AB  - For the non-magnetic system of Ag films on Ru(0001), we have measured the
      circular dichroism of photoelectrons emitted along the surface normal, the
      geometry typically used in photoemission electron microscopy. Photoemission
      spectra were acquired from micrometer-sized regions having uniformly thick Ag
      films on a single, atomically flat Ru terrace. For a single Ag layer, we find a
      circular dichroism that exceeds 6% at the d-derived band region around 4.5 eV
      binding energy. The dichroism decreases as the Ag film thickness increases to
      three atomic layers. We discuss the origin of the circular dichroism in terms of
      the symmetry lowering that can occur even in normal emission.

PMID- 21734332
TI  - Surface reconstruction of W2C(0001).
AB  - A single crystal surface of ditungsten carbide, W(2)C(0001) was investigated
      using low-energy (LEED) and high-energy electron diffraction, Auger electron
      spectroscopy, x-ray photoelectron spectroscopy (XPS), and high-resolution
      electron energy loss spectroscopy (HREELS). A new reconstruction, ?13 x ?13R +/-
      13.9?, was found as a clean surface structure after annealing the W(2)C at > 1900
      K. The surface carbon content is shown as larger than that in the bulk. Our
      preliminary results showed that the same structure is realized also on WC(0001).
      The same surface periodicity is described for an Mo(2)C(0001) LEED pattern in the
      literature. This reconstruction phase is presumably common on the (0001) surface
      of hexagonal group-6 transition-metal carbides. In the off-specular HREELS, an
      atomic vibration of 44.8 meV (361 cm( - 1)) appeared within the gap energy region
      of the bulk phonon bands, which was assigned to a surface carbon vibration
      perpendicular to the surface. One possible explanation of the low vibrational
      frequency is very low adsorption height of the surface carbon atoms.

PMID- 21734333
TI  - Simulations and measurements of transcranial low-frequency ultrasound therapy:
      skull-base heating and effective area of treatment.
AB  - Measurements of temperature elevations induced by sonications in a single intact
      cadaver skull filled with soft-tissue mimicking phantom material were performed
      using magnetic resonance thermometry. The sonications were done using a clinical
      transcranial ultrasound therapy device operating at 230 kHz and the measurements
      were compared with simulations done using a model incorporating both the
      longitudinal and shear wave propagation. Both the measurements and simulations
      showed that in some situations the temperature increase could be higher in the
      phantom material adjacent to the skull-base than at the focus, which could lead
      to undesired soft-tissue damage in treatment situations. On average the
      measurements of the sonicated locations, as well as the comparative simulations,
      showed 32 +/- 64% and 49 +/- 32% higher temperature elevations adjacent to the
      skull-base than at the focus, respectively. The simulation model was used to
      extend the measurements by simulating multiple sonications of brain tissue in
      five different skulls with and without correcting the aberrations caused by the
      skull on the ultrasound. Without aberration correction the closest sonications to
      the skulls that were treatable in any brain location without undesired tissue
      damage were at a distance of 19.1 +/- 2.6 mm. None of the sonications beyond a
      distance of 41.2 +/- 5.3 mm were found to cause undesired tissue damage. When
      using the aberration correction closest treatable, safe distances for sonications
      were found to be 16.0 +/- 1.6  and 38.8 +/- 3.8 mm, respectively. New active
      cooling of the skull-base through the nasal cavities was introduced and the
      treatment area was investigated. The closest treatable distance without
      aberration correction reduced to 17.4 +/- 1.9 mm with the new cooling method. All
      sonications beyond a distance of 39.7 +/- 6.6 mm were found treatable. With the
      aberration correction no difference in the closest treatable or the safety
      distance was found in comparison to sonications without nasal cavity cooling. To
      counteract undesired skull-base heating a new anti-focus within solid media was
      developed along with a new regularized phasing method. Mathematical bases for
      both the methods and simulations utilizing them were presented. It was found that
      utilizing the anti-focus in solid media and regularized phasing, the fraction of
      temperature increase of the brain tissue at the focus and the peak temperature
      increase adjacent to the skull-base can be increased from 1.00 to 1.95. This
      improves the efficiency of the sonication by reducing the energy transfer to the
      skull-base.

PMID- 21734334
TI  - Analysis of the local worst-case SAR exposure caused by an MRI multi-transmit
      body coil in anatomical models of the human body.
AB  - Multi-transmit coils are increasingly being employed in high-field magnetic
      resonance imaging, along with a growing interest in multi-transmit body coils.
      However, they can lead to an increase in whole-body and local specific absorption
      rate (SAR) compared to conventional body coils excited in circular polarization
      for the same total incident input power. In this study, the maximum increase of
      SAR for three significantly different human anatomies is investigated for a large
      3 T (128 MHz) multi-transmit body coil using numerical simulations and a
      (generalized) eigenvalue-based approach. The results demonstrate that the
      increase of SAR strongly depends on the anatomy. For the three models and
      normalization to the sum of the rung currents squared, the whole-body averaged
      SAR increases by up to a factor of 1.6 compared to conventional excitation and
      the peak spatial SAR (averaged over any 10 cm(3) of tissue) by up to 13.4. For
      some locations the local averaged SAR goes up as much as 800 times (130 when
      looking only at regions where it is above 1% of the peak spatial SAR). The ratio
      of the peak spatial SAR to the whole-body SAR increases by a factor of up to 47
      and can reach values above 800. Due to the potentially much larger power
      deposition, additional, preferably patient-specific, considerations are necessary
      to avoid injuries by such systems.

PMID- 21734335
TI  - Radiological characterization and water equivalency of genipin gel for x-ray and
      electron beam dosimetry.
AB  - The genipin radiochromic gel offers enormous potential as a three-dimensional
      dosimeter in advanced radiotherapy techniques. We have used several methods
      (including Monte Carlo simulation), to investigate the water equivalency of
      genipin gel by characterizing its radiological properties, including mass and
      electron densities, photon interaction cross sections, mass energy absorption
      coefficient, effective atomic number, collisional, radiative and total mass
      stopping powers and electron mass scattering power. Depth doses were also
      calculated for clinical kilovoltage and megavoltage x-ray beams as well as
      megavoltage electron beams. The mass density, electron density and effective
      atomic number of genipin were found to differ from water by less than 2%. For
      energies below 150 keV, photoelectric absorption cross sections are more than 3%
      higher than water due to the strong dependence on atomic number. Compton
      scattering and pair production interaction cross sections for genipin gel differ
      from water by less than 1%. The mass energy absorption coefficient is
      approximately 3% higher than water for energies <60 keV due to the dominance of
      photoelectric absorption in this energy range. The electron mass stopping power
      and mass scattering power differ from water by approximately 0.3%. X-ray depth
      dose curves for genipin gel agree to within 1% with those for water. Our results
      demonstrate that genipin gel can be considered water equivalent for kilovoltage
      and megavoltage x-ray beam dosimetry. For megavoltage electron beam dosimetry,
      however, our results suggest that a correction factor may be needed to convert
      measured dose in genipin gel to that of water, since differences in some
      radiological properties of up to 3% compared to water are observed. Our results
      indicate that genipin gel exhibits greater water equivalency than polymer gels
      and PRESAGE formulations.

PMID- 21734336
TI  - Toward efficient biomechanical-based deformable image registration of lungs for
      image-guided radiotherapy.
AB  - Both accuracy and efficiency are critical for the implementation of biomechanical
      model-based deformable registration in clinical practice. The focus of this
      investigation is to evaluate the potential of improving the efficiency of the
      deformable image registration of the human lungs without loss of accuracy. Three
      dimensional finite element models have been developed using image data of 14 lung
      cancer patients. Each model consists of two lungs, tumor and external body.
      Sliding of the lungs inside the chest cavity is modeled using a frictionless
      surface-based contact model. The effect of the type of element, finite
      deformation and elasticity on the accuracy and computing time is investigated.
      Linear and quadrilateral tetrahedral elements are used with linear and nonlinear
      geometric analysis. Two types of material properties are applied namely: elastic
      and hyperelastic. The accuracy of each of the four models is examined using a
      number of anatomical landmarks representing the vessels bifurcation points
      distributed across the lungs. The registration error is not significantly
      affected by the element type or linearity of analysis, with an average vector
      error of around 2.8 mm. The displacement differences between linear and nonlinear
      analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm
      is found in one of the nodes near the entrance of the bronchial tree into the
      lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8
      mm. However, the time required for the analysis is reduced from 95 min in the
      quadratic elements nonlinear geometry model to 3.4 min in the linear element
      linear geometry model. Therefore using linear tetrahedral elements with linear
      elastic materials and linear geometry is preferable for modeling the breathing
      motion of lungs for image-guided radiotherapy applications.

PMID- 21734337
TI  - Implications on clinical scenario of gold nanoparticle radiosensitization in
      regards to photon energy, nanoparticle size, concentration and location.
AB  - Gold nanoparticle (AuNP) radiosensitization represents a novel approach to
      enhance the effectiveness of ionizing radiation. Its efficiency varies widely
      with photon source energy and AuNP size, concentration, and intracellular
      localization. In this Monte Carlo study we explored the effects of those
      parameters to define the optimal clinical use of AuNPs. Photon sources included
      (103)Pd and (125)I brachytherapy seeds; (169)Yb, (192)Ir high dose rate sources,
      and external beam sources 300 kVp and 6 MV. AuNP sizes were 1.9, 5, 30, and 100
      nm. We observed a 10(3) increase in the rate of photoelectric absorption using
      (125)I compared to 6 MV. For a (125)I source, to double the dose requires
      concentrations of 5.33-6.26 mg g(-1) of Au or 7.10 * 10(4) 30 nm AuNPs per tumor
      cell. For 6 MV, concentrations of 1560-1760 mg g(-1) or 2.17 * 10(7) 30 nm AuNPs
      per cell are needed, which is not clinically achievable. Examining the proportion
      of energy transferred to escaping particles or internally absorbed in the
      nanoparticle suggests two clinical strategies: the first uses photon energies
      below the k-edge and takes advantage of the extremely localized Auger cascade. It
      requires small AuNPs conjugated to tumor targeted moieties and nuclear localizing
      sequences. The second, using photon sources above the k-edge, requires a higher
      gold concentration in the tumor region. In this approach, energy deposited by
      photoelectrons is the main contribution to radiosensitization; AuNP size and
      cellular localization are less relevant.

PMID- 21734338
TI  - Large-area hard magnetic L10-FePt nanopatterns by nanoimprint lithography.
AB  - Large-area hard magnetic L1(0)-FePt nanopatterns with out-of-plane texture were
      fabricated by using a top-down approach. For the fabrication process, ultraviolet
      nanoimprint lithography (UV-NIL) in combination with inductively coupled plasma
      reactive Ar-ion etching was used. By this technique a continuous L1(0)
      Fe(51)Pt(49) film was nanostructured into a regular arrangement of nanodots over
      an area of 4 mm(2). The dot dimension and distribution was specified by the
      stamp, resulting in a dot size of 60 nm and a periodicity of 150 nm. For the
      large-scale L1(0)-FePt nanopatterns, huge coercivities up to 4.31 T could be
      achieved. By means of magnetic force microscopy it could be verified that the
      nanodots were magnetically decoupled from each other and occurred in the single
      domain state with perpendicular magnetization.

PMID- 21734339
TI  - Minimizing the Gibbs-Thomson effect in the low-temperature plasma synthesis of
      thin Si nanowires.
AB  - An advanced combination of numerical models, including plasma sheath, ion- and
      radical-induced species creation and plasma heating effects on the surface and
      within a Au catalyst nanoparticle, is used to describe the catalyzed growth of Si
      nanowires in the sheath of a low-temperature and low-pressure plasma. These
      models have been used to explain the higher nanowire growth rates, low-energy
      barriers, much thinner Si nanowire nucleation and the less effective Gibbs
      Thomson effect in reactive plasma processes, compared with those of neutral gas
      thermal processes. The effects of variation in the plasma sheath parameters and
      substrate potential on Si nanowire nucleation and growth have also been
      investigated. It is shown that increasing the plasma-related effects leads to
      decreases in the nucleation energy barrier and the critical nanoparticle radius,
      with the Gibbs-Thomson effect diminished, even at low temperatures. The results
      obtained are consistent with available experimental results and open a path
      toward the energy- and matter-efficient nucleation and growth of a broad range of
      one-dimensional quantum structures.

PMID- 21734340
TI  - Correlation between eicosanoids in bronchoalveolar lavage fluid and in exhaled
      breath condensate.
AB  - Exhaled breath condensate (EBC) has been increasingly used as a new and non
      invasive method to study airway inflammation. In this study we have compared the
      concentrations of lipid mediators in EBC with concentrations in bronchoalveolar
      lavage fluid (BALF). We included 37 patients undergoing bronchoscopy (12
      sarcoidosis, 12 COPD, 6 lung cancer, 5 chronic cough, 1 Wegener's granulomatosis,
      1 sclerodermia). Patients were not allowed to have exacerbation or any change in
      concomitant medication for at least 4 weeks prior to the study. In all patients,
      EBC was collected immediately prior to the bronchoscopy. The levels of cys-LTs,
      LTB<formula>_{4}</formula>, 8-isoprostane were significantly higher in BALF
      compared to EBC (p < 0.0001, p< 0.001, p< 0.0001 for cys-LTs, LTB4, 8-isoprostane
      respectively). Moreover, there was a strong positive correlation between both
      leukotriene B<formula>_{4}</formula> and 8-isoprostane in BALF and EBC (r=0.53
      and r=0.79, p< 0.01, respectively) in patients with sarcoidosis and COPD but
      there was no correlation between eicosanoids BALF and EBC in patients with
      chronic cough and lung cancer. This is the first study to compare EBC and BALF in
      different lung diseases which demonstrated significant correlations between the
      levels of eicosanoids in BALF and EBC in patients with COPD and sarcoidosis. EBC
      may be useful in measuring inflammation in several inflammatory lung diseases.

PMID- 21734341
TI  - alpha-defensin 1-3 and alpha-defensin 4 as predictive markers of imatinib
      resistance and relapse in CML patients.
AB  - OBJECTIVE: Imatinib mesylate is a tyrosine kinase inhibitor used as first line
      treatment in chronic myeloid leukaemia. Despite a remarkable effectiveness,
      treatment failure cases have been reported in 20 percent of CML patients. The
      identification of biomarkers which can predict the response to imatinib is our
      point of interest. METHODS: Gene expression profiling microarray was carried out
      on secondary imatinib resistant patients. Longitudinal studies were performed on
      imatinib treated responder/resistant patients. Then, Q-RT/PCR studies were
      realized on patients prior imatinib initiation. RESULTS: For imatinib responder
      patients, we observed a strong and lasting decrease of alpha-defensin 1-3 and
      alpha-defensin 4 expression. For relapse patients, we observed a dramatic
      increase of alpha-defensin 1-3 and alpha-defensin 4 expression before BCR-ABL
      transcript increase. Moreover, before imatinib initiation, alpha-defensin 1-3 and
      alpha-defensin 4 expression was significantly lower in the resistant group than
      in the responder group. CONCLUSION: The variation of expression of alpha-defensin
      1-3 and alpha-defensin 4 in peripheral blood is associated with imatinib
      resistance and may reflect an adequate immune control of the disease. Monitoring
      of alpha-defensin 1-3 and alpha-defensin 4 could be helpful to predict the
      patients who are not going to respond to the treatment.

PMID- 21734342
TI  - Mcl-1 expression is up-regulated in malignancies of the parotid gland.
AB  - The anti-apoptotic protein Mcl-1 is highly expressed in various types of
      malignant tumors. Overexpression is reported to correlate with poor prognosis and
      disease progression. We report the expression levels of Mcl-1 in tumor samples of
      the parotid gland. A retrospective study containing 108 patients was performed. A
      tissue microarray of six malignancies of the parotid gland and pleomorphic
      adenoma as control was constructed. Parotid gland tumor samples were
      immunohistochemically stained for Mcl-1 and expression intensities were assessed.
      Statistical analysis included correlation to patients' clinical data and
      comparison of malignancies to the adenoma. All malignancies had significantly
      higher expression of Mcl-1 than the pleomorphic adenomas. The intensity, however,
      had no significant correlation to overall survival. Our immunohistochemical
      findings indicate that parotid gland malignancies produce high levels of Mcl-1
      protein. Therefore, Mcl-1 might serve as a predictive co-marker in tumors of the
      parotid gland.

PMID- 21734343
TI  - Detection of autoantibodies against glycosylated-DNA in diabetic subjects: Its
      possible correlation with HbA(1C).
AB  - AIMS: The vascular tissues have a long memory of their previous glycemic control
      and intervention studies have demonstrated that microvascular complications are
      highly correlated with mean glycemic control as measured by glycolated hemoglobin
      A1C ( HbA1c)The present study was carried out to evaluate the autoantibodies
      against glycosylated DNA (DNA-AGEs) in diabetic sera to see if the level of HbA1c
      has correlation with the activity of DNA-AGEs, another marker of chronic
      glycemia. METHODS: Glucose-6-phosphate induced glycosylation of native DNA was
      studied in 150 diabetic sera (T1DM=9, T2DM=141) by spectroscopic techniques (UV
      and fluorescence) and agarose gel electrophoresis. Direct binding and inhibition
      enzyme immunoassays were carried out to evaluate binding and specificity of anti
      glycated-DNA autoantibodies (anti-DNA-AGE autoantibodies) in sera of diabetes
      patients. A quantitative estimation of HbA1c was carried out in normal and
      diabetes sera. RESULTS: Anti-DNA-AGEs autoantibodies in 55% of diabetic sera
      (85/150) showed more binding with glycated-DNA compared to native DNA which was
      subjected to inhibition ELISA indicating true interaction of these autoantibodies
      in diabetes with glycated DNA. Higher binding with glycosylated-DNA against
      native-DNA was observed in subjects with HbA1c of 9.8 +/- 3.3% compared to those
      with HbA1c of 7.7 +/- 1.7% (p< 0.001). Linear correlation analysis showed that
      mean absorbance difference was significantly related to HbA1c (r=0.486, p<
      0.001), nephropathy (r= 0.239, p< 0.003), retinopathy (r=0.165, p< 0.05).
      CONCLUSIONS: Autoantibodies against glycosylated DNA were correlated with HbA1c
      and microvascular complications and may be useful as another biomarker for
      assessment of chronic glycemia.

PMID- 21734344
TI  - Asymmetric dimethylarginine (ADMA) levels display a morning peak in patients with
      acute myocardial infarction.
AB  - High Asymmetric Dimethylarginine (ADMA) levels are associated with increased
      platelet activity, elevated blood pressure, vasoconstriction and impaired
      vascular relaxation. We hypothesized that the myocardial infarction morning peak
      of occurrence is closely related to a morning peak of ADMA levels. We performed a
      cross-sectional study among patients with documented myocardial infarction who
      had been enrolled in the prospective MISSION! Intervention Study. In total, serum
      ADMA levels were measured in their acute setting of myocardial infarction in 120
      patients. The frequency of myocardial infarction onset of symptoms and emergency
      coronary catheterization and the ADMA levels displayed a similar daily pattern
      with a morning peak between 06:00-11:59 h. The absolute ADMA levels peak was
      between 06:00-07:59 h with a median (interquartile range) peak value of 1.01
      (0.84-1.21) MUmol/L for the n=9 patients vs. 0.75 (0.61-0.89) MUmol/L for the
      remaining 111 patients admitted throughout the rest of the 24-hour interval
      (p=0.003 for between groups comparison). The amplitude (95% 0.08 MUmol/L (0.004
      0.16) with p=0.042 for statistic model significance. In conclusion, ADMA levels
      display a 24-hour variation with a significant morning peak in patients with
      acute myocardial infarction. These findings may relate ADMA levels to the acute
      onset of thrombotic cardiovascular events.

PMID- 21734345
TI  - Combined analysis of EPHX1, GSTP1, GSTM1 and GSTT1 gene polymorphisms in relation
      to chronic obstructive pulmonary disease risk and lung function impairment.
AB  - Smoking is considered as the major causal factor of chronic obstructive pulmonary
      disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers
      develops COPD. This suggests important contribution of other factors such as
      genetic predisposing. Our objective was to investigate combined role of EPHX1,
      GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung
      function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms
      were assessed in 234 COPD patients and 182 healthy controls from Tunisia.
      Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val)
      polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1
      genes was determined using multiplex PCR. Analysis of combinations showed a
      significant association of 113His/His EPHX1/null-GSTM1 (OR=4.07) and null
      GSTM1/105Val/Val GSTP1 (OR =3.56) genotypes with increased risk of COPD
      (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val
      GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1
      genotypes were related to emphysema (respectively P=0.01; P=0.009; P=0.008 and
      P=0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a
      significant association with the decrease of Delta FEV1 in patients (P =0.028).In
      conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic
      polymorphisms may play a significant role in the development of COPD, emphysema
      and decline of the lung function.

PMID- 21734346
TI  - High-resolution melting curve analysis for high-throughput genotyping of
      NOD2/CARD15 mutations and distribution of these mutations in Slovenian
      inflammatory bowel diseases patients.
AB  - Inflammatory bowel diseases (IBD) are usually classified into Crohn's disease
      (CD) and ulcerative colitis (UC). NOD2/CARD15 was the first identified CD
      susceptibility gene and was confirmed as the most potent disease gene in CD
      pathogenesis. Three NOD2/CARD15 variants, namely two missense polymorphisms R702W
      (rs2066844) and G908R (rs2066845), and a frame shift polymorphism L1007fs
      (rs2066847), were associated with CD in Caucasian populations. High resolution
      melting analysis (HRMA) with saturation LCGreen dyes was previously reported as a
      simple, inexpensive, accurate and sensitive method for genotyping and/or scanning
      of rare variants. For this reasons we used qPCR-HRMA for genotyping NOD2/CARD15
      variants in 588 Slovenian IBD patients and 256 healthy controls. PCR-RFLP was
      used as a reference method for genotyping of clinical samples. The optimization
      of an HRM experiment required careful design and adjustment of main parameters,
      such as primer concentration, MgCl<formula>_{2}</formula> concentration, probe
      design and template DNA concentration. Different HRMA approaches were tested and
      used to develop a reliable and low-cost SNP genotyping assays for polymorphisms
      in NOD2/CARD15 gene. Direct HRMA was the fastest and cheapest HRMA approach for
      L1007fs and R702W polymorphisms, yet for G908R polymorphism sufficient
      reliability was achieved after introduction of unlabeled probe. In association
      analysis, we found statistically significant association of L1007fs (p =0.001,
      OR=3.011, CI95%=1.494-6.071) and G908R (p=2.62 * 10<formula>^{-4}</formula>,
      OR=14.117, CI95%= 1.884-105.799) polymorphisms with CD patients. At least one of
      NOD2/CARD15 polymorphisms was found in 78/354 (22.03% (12.69%) in UC patients and
      in 26/256 (10.15%) in healthy controls. We have successfully implemented
      NOD2/CARD15 HRMA assays, which may contribute to the development of genetic
      profiles for risk prediction of developing CD and for differential diagnosis of
      CD vs. UC.

PMID- 21734347
TI  - Statins: the role in the treatment and prevention of Alzheimer's
      neurodegeneration.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease commonly seen
      in the elderly and is characterized by progressive cognitive and physical
      decline. Current understanding of AD pathogenesis revolves around amyloid-beta
      peptide (Abeta), a product of the sequential proteolytic cleavage of the
      transmembrane amyloid-beta protein precursor (AbetaPP) by beta- and gamma
      secretase, enzymes found predominantly in the cholesterol rich micro domains of
      the cell membrane. Several risk factors for AD are associated with cholesterol
      metabolism, including dyslipidaemia, coronary artery and cerebrovascular disease.
      Statins are widely prescribed for their cholesterol lowering ability and show a
      favorable side effect profile overall. By competitive inhibition of hydroxymethyl
      co-enzyme A-reductase, statins reduce the production of cholesterol and
      isoprenoid intermediates including geranylgeranyl and farnesyl pyrophosphate.
      These isoprenoids modify recently translated proteins such as small GTPase
      molecules that are essential in numerous cell-signaling pathways, including
      vesicular trafficking and inflammation. In experimental models of AD, statins
      reduce the production of Abeta by disrupting secretase enzyme function and by
      reducing neuroinflammation. Furthermore, epidemiological studies suggest that
      statins may reduce the incidence of AD. Consequently, statins, secondary of their
      anti-hypercholesterolaemic, plieotropic and anti-inflammatory effects, are being
      investigated for a potential therapeutic role. This review will discuss evidence
      for the role of statins in the treatment and prevention of AD neurodegeneration.

PMID- 21734348
TI  - Von Willebrand factor, and soluble intercellular and vascular cell adhesion
      molecules as indices of endothelial activation in patients with congenital
      hypothyroidism.
AB  - Considering the high prevalence of congenital hypothyroidism (CH) in Isfahan, the
      possible involvement of endothelial dysfunction in the pathogenesis of CH and the
      lack of studies in this field, the aim of this study was to determine the
      endothelial function in CH patients. METHODS: During this case-control study, the
      endothelial function in CH neonates and in those with normal screening results
      was evaluated during a CH screening program in Isfahan. Peripheral blood samples
      were obtained for measurement of the von Willebrand factor (vWf), and
      intercellular and vascular cell adhesion molecule (ICAM and VCAM). In CH patients
      these biomarkers were measured twice: before and 4 weeks after treatment.
      RESULTS: In this study, 56 neonates were evaluated: 30 of them were neonates with
      normal screening results and 26 were diagnosed with CH and classified into two
      groups according to their TSH levels. The mean ICAM and VCAM were higher in CH
      patients than in the control group (p < 0.05). The mean ICAM and VCAM decreased
      significantly after treatment in CH patients (p < 0.05). There is no significant
      relationship between TSH, ICAM, VCAM and vWf (p > 0.05). CONCLUSION: The findings
      of this study demonstrate the possible involvement of the endothelial system in
      the pathogenesis of CH and its cardiovascular complications. Further studies with
      a larger sample size and with the measurement of other endothelial function
      markers are needed.

PMID- 21734349
TI  - Bronchopulmonary zygomycosis.

PMID- 21734350
TI  - Influenza virus hemagglutinin: a model for protein N-glycosylation in recombinant
      Escherichia coli.
AB  - BACKGROUND: The hemagglutinin molecule of influenza virus is considered as an
      ideal model to study biological processes as well as the effect of glycosylation
      on the function of glycoproteins. OBJECTIVES: The large subunit of the influenza
      virus A/New Caledonia/20/99 (H1N1) hemagglutinin (HA1) was expressed in
      recombinant Escherichia coli containing the glycosylation system of Campylobacter
      jejuni. This viral glycoprotein contains glycosylation motifs recognized by
      prokaryotic and eukaryotic oligosaccharyltransferases. METHODS: In order to
      express the hemagglutinin large subunit gene, the gene was amplified using
      reverse transcription polymerase chain reaction (RT-PCR), and it was cloned in
      pET22b for periplasmic expression. RESULTS: Western blotting and lectin blotting
      bands confirmed glycosylation of the HA1 in recombinant E. coli. CONCLUSION: Such
      a successful accomplishment of hemagglutinin expression in recombinant E. coli
      can be used to construct carbohydrates in hemagglutinin molecules of different
      strains in order to produce effective antigens for vaccine and rapid diagnostic
      kits against new emerging viruses.

PMID- 21734351
TI  - Mycobacterium marinum epididymoorchitis: case report and literature review.
AB  - Mycobacterium marinum is the most frequent non-tuberculous Mycobacterium in
      humans. We report the first ever described case of epididymoorchitis resulting
      from hematogenous spread of M. marinum from hand oligoarthritis. This was
      initially mistaken for rheumatoid disease and methylprednisolone-induced
      immunosuppression led to hematogenous spread of infection to the testis and
      epididymis.

PMID- 21734352
TI  - Identification of two immunoreactive peptides useful for the detection of porcine
      astrovirus.
AB  - Porcine astroviruses (PAstVs) are small RNA viruses associated with
      gastroenteritis. The capsid polyprotein of PAstVs, human (HAstVs) and feline
      (FAstVs) AstVs has a high similarity at the N-terminus before residue 415.
      Previous results showed the cross-detection of PAstVs and HAstVs from diarrheal
      samples using a commercial ELISA test that uses a monoclonal antibody to capture
      HAstVs, suggesting the existence of common immunoreactive epitopes between these
      two virus types. In this study, we seeked immunoreactive peptides located in the
      PAstV capsid that may be potentially used for their specific detection. The
      variability and hydrophobicity of a short fragment of 132 amino acids were
      analyzed using several capsid sequences of PAstVs and HAstVs. Peptides TATL, SLNP
      and IDIV were selected, synthesized and inoculated into rabbits. Pre- and
      hyperimmune sera were collected and their reactivity was examined by immunoassay
      and immunofluorescence against two wild-type strains of PAstV adapted to grow in
      cell culture, observing reactivity in two of the sera. Finally, the possible
      cross-reactivity of the sera against HAstVs was partially ruled out using HAstV8.
      Our data suggest that TATLGTIGSNSSGKTELEAC and IDIVVGKAATFNLKASDLSGP peptides
      represent immunoreactive regions useful for the specific detection of PAstVs.

PMID- 21734353
TI  - Amino acid substitution in HCV core/NS5A region and genetic variation near IL28B
      gene affect treatment efficacy to interferon plus ribavirin combination therapy.
AB  - OBJECTIVE: To evaluate predictive factors of treatment efficacy to interferon
      (IFN)/ribavirin in patients infected with HCV genotype 1b (HCV-1b). METHODS: This
      study investigated pretreatment predictors, including viral- (aa substitutions in
      core aa 70/91 and NS5A-ISDR/IRRDR) and host-related factors (genetic variation
      near IL28B gene), to 48-week IFN/ribavirin in 490 Japanese adults infected with
      HCV-1b. RESULTS: The proportion of patients who showed end-of-treatment response
      (ETR), sustained virological response (SVR), and SVR after ETR was 76, 54, and
      76%, respectively. There was a significant positive correlation between the
      number of aa substitutions in ISDR and those in IRRDR. Concerning the
      substitution of core aa 91, the number of aa substitutions in ISDR/IRRDR of
      patients with Leu91 was significantly higher than that of patients with Met91.
      Furthermore, levels of viremia were influenced by aa substitutions in core aa 91
      and ISDR/IRRDR. By multivariate analysis, rs8099917 genotype was an important
      predictor of ETR and SVR. With regard to viral factors, core aa 70/91 was an
      important predictor of ETR, and SVR after ETR. ISDR was an important predictor of
      SVR, and SVR after ETR. CONCLUSION: aa substitution in core/NS5A region and
      genetic variation near IL28B were important predictors of treatment efficacy to
      IFN/ribavirin.

PMID- 21734354
TI  - Efficacy of noninvasive positive pressure ventilation in elderly patients with
      acute hypercapnic respiratory failure.
AB  - BACKGROUND: There have been no reports on the efficacy of noninvasive positive
      pressure ventilation (NPPV) in elderly patients. OBJECTIVES: The purpose of this
      study was to clarify the efficacy and identify the predictors of a successful
      outcome of NPPV in patients over the age of 75 years with acute hypercapnic
      respiratory failure (AHRF). METHODS: We retrospectively evaluated the data of 42
      patients (21 men) with AHRF who were treated at our unit. The patients were
      divided into survivor and nonsurvivor groups, and the clinical parameters
      measured prior to the initiation of NPPV were compared between the 2 groups.
      RESULTS: The mean age of the patients was 83.0 +/- 6.3 years. The etiology of the
      respiratory failure was acute exacerbation of chronic obstructive pulmonary
      disease in 19 patients, acute cardiogenic pulmonary edema in 18 patients,
      idiopathic pulmonary fibrosis in 3 patients, sequelae of tuberculosis in 1
      patient, and asthma in 1 patient. Of the 42 patients, 33 (78.6%) survived. All
      patients with a Glasgow Coma Scale (GCS) score >=9 and/or an APACHE II score <29
      survived after the initiation of NPPV. CONCLUSION: An APACHE II score <29 and a
      GCS score >=9 were predictors of a successful outcome of NPPV in elderly people.

PMID- 21734355
TI  - Neuropeptides as pleiotropic modulators of the immune response.
AB  - Although necessary to eliminate pathogens, inflammation can lead to serious
      deleterious effects in the host if left unchecked. During the inflammatory
      response, further damage may arise from potential autoimmune responses occurring
      when the immune cells and molecules that respond to pathogen-derived antigens
      also react to self-antigens. In this sense, the identification of endogenous
      factors that control exacerbated immune responses is a key goal for the
      development of new therapeutic approaches for inflammatory and autoimmune
      diseases. Some neuropeptides that are produced during the ongoing inflammatory
      response have emerged as endogenous anti-inflammatory agents that could
      collaborate in tuning the balanced steady state of the immune system. These
      neuropeptides participate in maintaining immune tolerance through two distinct
      mechanisms: by regulating the balance between pro-inflammatory and anti
      inflammatory factors, and by inducing the emergence of regulatory T cells with
      suppressive activity against autoreactive T cell effectors. Indeed, a functioning
      neuropeptide system contributes to general health, and alterations in the levels
      of these neuropeptides and/or their receptors lead to changes in susceptibility
      to inflammatory and autoimmune diseases. Recently, we found that some
      neuropeptides also have antimicrobial and antiparasitic actions, suggesting that
      they could act as primary mediators of innate defense, even in the most primitive
      organisms. In this review, we use the vasoactive intestinal peptide as example of
      an immunomodulatory neuropeptide to summarize the most relevant data found for
      other neuropeptides with similar characteristics, including adrenomedullin,
      urocortin, cortistatin and ghrelin.

PMID- 21734356
TI  - Cytomegalovirus gB genotype distribution in Mexican children undergoing
      allogeneic bone marrow transplantation.
AB  - We used nested multiplex polymerase chain reaction to determine the distribution
      of cytomegalovirus gB genotype in 30 Mexican children undergoing bone marrow
      transplantation. The genotypes were: gB1, 9/30 (30%); gB2, 8/30 (27%); gB3, 4/30
      (13%), and gB4, 1/30 (3%); mixed genotypes were identified in 8/30 patients
      (27%). We conclude that the predominant genotypes identified were gB2 and gB1.
      The gB5 genotype was not detected, and a high proportion of mixed genotype was
      found.

PMID- 21734357
TI  - Genetics in health care: an overview of current and emerging models.
AB  - BACKGROUND: With advances in genetic and genomic medicine, the optimal
      integration of genetic services into the health care system remains of major
      concern in many countries. OBJECTIVES: To review the current organisation of
      genetic services, mostly in Europe, North America and Australia, explore emerging
      service delivery models, and probe challenges inherent in the transition process.
      METHODS: We conducted a literature review of genetics in clinical practice:
      testing, diagnosis, counselling, and treatment. We examined the basic structures
      of genetic services, examples of integrated networks, and existing professional
      resources. We investigated services belonging traditionally in medical genetics
      as well as those developed for more common diseases. RESULTS: Multidisciplinary
      specialist clinics and coordinated services appeared to be key to delivering
      proper care in rare genetic disorders. For oncogenetics, neurogenetics and
      cardiogenetics, interprofessional collaboration between geneticists and other
      specialists seemed to be favoured. On the other hand, there was also a tendency
      toward the integration of genetic services directly into primary care. Among the
      most pressing challenges was the morphing of paediatric care into adult care.
      CONCLUSION: The coordination of activities between professionals in first-,
      second-, and third-line medical care is a primary objective calling for the
      reconfiguration of professional roles and responsibilities. This entails the
      forging of new relationships as well as an enhanced sharing of expertise and
      genetic information, including information regarding services. Barriers to
      overcome include the redistribution of roles, sharing of data and databases, and
      the lack of preparedness of non-genetics professionals and of the health care
      system in general.

PMID- 21734358
TI  - Lumbar incisional hernia of the kidney after laparoscopic adrenalectomy in a
      patient with Cushing's syndrome.
AB  - We report a first case of lumbar herniation of a kidney after laparoscopic
      adrenalectomy in a patient with Cushing's syndrome. A 59-year-old woman underwent
      separate laparoscopic adrenalectomies for right adrenal Cushing's syndrome and
      left primary aldosteronism. She consulted our department with a 6-month history
      of intermittent left back pain, starting 8 months after the second operation.
      Magnetic resonance imaging showed herniation of the left kidney through a defect
      of the lumbodorsal fascia.

PMID- 21734359
TI  - Ureterorenoscopy: avoiding and managing the complications.
AB  - Retrograde exploration of the ureter and kidneys is currently a widely used and
      well-established procedure to deal with problems of a diagnostic and therapeutic
      nature with reduced invasiveness. The process of miniaturizing the instruments
      combined with the steady improvement in video quality has continuously amplified
      its potential applications, maintaining the procedure safe and rapid. During an
      operation, however, unexpected events may condition a change to the programme or
      determine the onset of even more serious complications. Our aim is to analyze
      such events and complications and recommend potential solutions to prevent and/or
      deal with such happenings.

PMID- 21734360
TI  - Health-related internet use in older primary care patients.
AB  - BACKGROUND: Adults aged 65 years and older stand to benefit from the accumulating
      wealth of Internet-based health resources, including online interventions to
      assist in the self-management of chronic health conditions. However, concerns
      have been expressed that lesser Internet use and familiarity among older adults
      may limit the utility of web-based health interventions in older age groups. As
      these interventions become more prevalent, it is important to understand older
      adults' receptivity to using the Internet as a tool in managing healthcare.
      OBJECTIVE: The purpose of the present study was to gauge the extent to which
      older primary care patients are receptive to using web-based health resources,
      and to explore how health-related Internet use may be related to patient
      characteristics such as age, income, and health and mental health status.
      METHODS: We surveyed 50 adults aged 65 years and older in a Veterans
      Administration primary care clinic regarding: (1) Internet use for any purpose,
      (2) Internet use to obtain health or mental-related information, and (3) interest
      in using Internet-based interventions to address various health-related needs. A
      substantial proportion of respondents were in their 70s, 80s, and 90s, and many
      had multiple medical conditions. RESULTS: Nearly three-quarters of older primary
      care patients in our sample were regular Internet users and over half had
      experience in using the Internet to search for health information. The majority
      of Internet users endorsed an interest in using web-based resources to manage
      various aspects of their health and mental healthcare. CONCLUSIONS: Our results
      support the conclusion that older primary care patients, including those among
      the oldest-old and those with multiple medical conditions, are amenable to using
      the Internet as a means of enhancing healthcare.

PMID- 21734361
TI  - New recurrent chromosome alterations in patients with multiple myeloma and plasma
      cell leukemia.
AB  - Chromosome abnormalities detected in metaphases from multiple myeloma (MM) cells
      have a clear impact on prognosis and response to therapy. Thirteen out of 50
      (26%) patients with plasma cell disorders and abnormal karyotypes (11 with MM and
      2 with plasma cell leukemia (PCL)) were selected for inclusion in the present
      report based on the presence of karyotypes with new and/or infrequent structural
      aberrations. Thirty-three new rearrangements, including a novel recurrent
      aberration: psu dic(5;1)(q35;q10), were detected. Chromosome 1 was the most
      frequently involved. Gains of genetic material (57%) were noted more frequently
      than losses (43%). Three rearrangements that were observed only once in the
      literature appear to be recurrent from our data: del(16)(q13), del(5)(p13) and
      i(3)(q10), the latter being a single structural aberration in the karyotype.
      Clinical parameters from our series were compared with 2 control groups: 20 MM
      cases with recurrent aberrations in MM/PCL with a similar distribution of
      abnormalities associated with poor prognosis (group 1), and 40 with normal
      karyotypes and fluorescence in situ hybridization analysis (group 2).
      Significantly increased serum calcium levels (p = 0.022) in patients with new
      and/or infrequent chromosome changes with respect to both control groups, and a
      higher percentage of bone marrow plasma cell infiltration (p = 0.005), beta(2)
      microglobulin, and lactate dehydrogenase levels (p < 0.0001) compared to group 2
      were observed. Our results suggest that some of these novel rearrangements may be
      capable to deregulate genetic mechanisms related to the development and/or
      progression of the disease. The finding of new recurrent aberrations supports
      this hypothesis.

PMID- 21734362
TI  - Overexpression of Lis1 in different stages of spermatogenesis does not result in
      an aberrant phenotype.
AB  - Previous studies showed that in the mouse mutant Lis1(GT/GT) gene trap
      integration in intron 2 of Lis1 gene leads to male infertility in homozygous
      Lis1(GT/GT) mice. We further analyzed this line and could confirm the suggested
      downregulation of a testis-specific Lis1 transcript in mutant animals in a
      quantitative manner. Moreover, we analyzed the gene trap mutation on different
      genetic backgrounds in incipient congenic animals and could exclude a genetic
      background effect. To gain further insights into the role and requirement of LIS1
      in spermatogenesis, 3 transgenic lines were generated, that overexpress Lis1
      under control of the testis-specific promoters hEF-1alpha, which is exclusively
      active in spermatogonial cells, PGK2, which is active in pachytene spermatocytes
      and following stages of spermatogenesis, and Tnp2 which is active in round
      spermatids and following stages of spermatogenesis, respectively. All 3
      transgenic lines remained fertile and testis sections displayed no abnormalities.
      To overcome the infertility of Lis1(GT/GT) males, these transgenic Lis1
      overexpressing animals were mated with Lis1(GT/GT) mice to generate 'rescued'
      Lis1(GT/GT)/Lis1(Tpos) males. 'Rescued' animals from all transgenic lines
      remained infertile, thus overexpression of Lis1 in different stages of
      spermatogenesis could not rescue the infertility phenotype of homozygous gene
      trap males.

PMID- 21734363
TI  - Cytotaxonomy, morphology and ecology of the Simulium nobile species group
      (Diptera: Simuliidae) in Thailand.
AB  - The polytene chromosomes of 512 larvae of the Simulium nobile species group
      collected from 16 stream sites in northern, central and southern Thailand were
      examined. Band-by- band comparisons relative to the established standard
      chromosome map for the subgenus Simulium distinguished the 2 species of this
      group, S. nobile and S. nodosum. The differences are mainly due to the position
      of the nucleolar organizer, pseudochromocenter, and fixed and polymorphic
      inversions. S. nobile is a monomorphic species, while S. nodosum is a polymorphic
      species. The morphology of these taxa is described based on the gill filaments
      and the color of the antennae and female genitalia. S. nobile is distributed in
      southern Thailand at low altitudes, whereas the distribution of S. nodosum is in
      the north at higher altitudes.

PMID- 21734364
TI  - Telomeres in trisomy 21 amniocytes.
AB  - Individuals with trisomy 21 have an increased risk of developing leukemia and
      premature dementia. They also have a higher rate of telomere loss. The aim of the
      study was to compare telomere length and the hTERC gene copy number, which
      encodes the telomerase RNA subunit, in amniocytes of trisomy 21 conceptions and
      normal pregnancies. A quantitative fluorescence-in-situ protocol (Q-FISH) was
      used to compare telomere length in amniocytes cultured from 11 trisomy 21
      conceptions and from 14 normal pregnancies. Quantification was conducted using
      novel computer software. Fluorescence in situ hybridization (FISH) was used to
      assess the percentage of cells with additional copies of hTERC. We found that the
      immunofluorescence intensity, which represents telomere length, was significantly
      lower in amniocytes from trisomy 21 conceptions compared to the control group.
      The trisomy 21 group had a higher number of cells with additional copies of
      hTERC. This observation could be one of the cytogenetic parameters that represent
      a state of genetic instability and might play a role in the pathomechanism of
      typical features of Down syndrome, such as dementia and malignancy.

PMID- 21734365
TI  - Diffuse large B cell lymphoma complicating total knee arthroplasty: case report
      and literature review of the association of diffuse large B cell lymphoma with
      joint replacement.
AB  - Primary lymphoma of bone is extremely rare. There are increasing reports of
      lymphoma arising in bone adjacent to metallic prostheses. Herein, we describe the
      case of a 76-year-old man who developed diffuse large B cell lymphoma in the
      tibia 3 years after total knee arthroplasty for osteoarthritis. A review of the
      literature has identified 11 other cases of lymphoma arising in the context of
      orthopaedic metallic implants. To our knowledge this is the first reported case
      of a primary lymphoma arising in bone adjacent to a knee prosthesis. Possible
      pathogenetic mechanisms may include chronic antigenic stimulation of lymphocytes,
      proliferation of EBV-infected B lymphocytes, and direct mutagenic effects of
      metallic ions. Further research is required to investigate this intriguing link
      between metallic orthopaedic prostheses and localized lymphoma.

PMID- 21734367
TI  - Suppressors of cytokine signaling inhibit tubular epithelial cell-myofibroblast
      transdifferentiation.
AB  - BACKGROUND/AIMS: Tubular epithelial cell-myofibroblast transdifferentiation
      (TEMT) can be induced by diverse cytokines. The suppressors of cytokine signaling
      (SOCS) proteins negatively regulate cytokine signaling. This study is aimed at
      examining the role of SOCS-1 and SOCS-3 in TEMT induced by cytokines. METHODS:
      The cell ultrastructure was observed using transmission electron microscopy. The
      protein and mRNA levels of cytokeratin 18 (CK18) and alpha-smooth muscle actin
      (alpha-SMA) were detected by immunocytochemistry, Western blot and real-time PCR.
      The levels of phosphorylated-signal transducer and activator of transcription (p
      STAT) 1 and 3 were detected by Western blot. The protein and mRNA levels of SOCS
      1 and SOCS-3 were detected by Western blot and real-time PCR. The levels of
      collagen type I and fibronectin (FN) were determined by ELISA. RESULTS:
      Interleukin-1beta (IL-1beta) and oncostatin M (OSM) were able to downregulate
      CK18 expression and upregulate alpha-SMA, p-STAT1, p-STAT3, collagen type I and
      FN expression in cultured human renal proximal tubular epithelial cells (HKCs),
      whereas pretreatment with AG490 prevented these expression changes from
      occurring. All of the changes induced by IL-1beta or OSM could be decreased by
      SOCS-1 and SOCS-3 overexpression, and were increased by SOCS-1 and SOCS-3
      knockdown. CONCLUSIONS: SOCS-1 and SOCS-3 can prevent tubulointerstitial fibrosis
      by inhibiting TEMT, which may be connected with the activation of STAT1 and
      STAT3.

PMID- 21734366
TI  - Relationship between stage of kidney disease and incident heart failure in older
      adults.
AB  - BACKGROUND: The relationship between stage of chronic kidney disease (CKD) and
      incident heart failure (HF) remains unclear. METHODS: Of the 5,795 community
      dwelling adults >=65 years in the Cardiovascular Health Study, 5,450 were free of
      prevalent HF and had baseline estimated glomerular filtration rate (eGFR:
      ml/min/1.73 m(2)) data. Of these, 898 (16%) had CKD 3A (eGFR 45-59 ml/min/1.73
      m(2)) and 242 (4%) had CKD stage >=3B (eGFR <45 ml/min/1.73 m(2)). Data on
      baseline proteinuria were not available and 4,310 (79%) individuals with eGFR
      >=60 ml/min/1.73 m(2) were considered to have no CKD. Propensity scores estimated
      separately for CKD 3A and >=3B were used to assemble two cohorts of 1,714 (857
      pairs with CKD 3A and no CKD) and 557 participants (148 CKD >=3B and 409 no CKD),
      respectively, balanced on 50 baseline characteristics. RESULTS: During 13 years
      of follow-up, centrally-adjudicated incident HF occurred in 19, 24 and 38% of pre
      match participants without CKD (reference), with CKD 3A [unadjusted hazard ratio
      (HR) 1.40; 95% confidence interval (CI) 1.20-1.63; p < 0.001] and with CKD >=3B
      (HR 3.37; 95% CI 2.71-4.18; p < 0.001), respectively. In contrast, among matched
      participants, incident HF occurred in 23 and 23% of those with CKD 3A and no CKD,
      respectively (HR 1.03; 95% CI 0.85-1.26; p = 0.746), and 36 and 28% of those with
      CKD >=3B and no CKD, respectively (HR 1.44; 95% CI 1.04-2.00; p = 0.027).
      CONCLUSIONS: Among community-dwelling older adults, CKD is a marker of incident
      HF regardless of stage; however, CKD >=3B, not CKD 3A, has a modest independent
      association with incident HF.

PMID- 21734368
TI  - Inhibitory effects of rosiglitazone on lipopolysaccharide-induced inflammation in
      a murine model and HK-2 cells.
AB  - BACKGROUND: Inflammation may play an important role in the pathogenesis of kidney
      disease. Agonists of the peroxisome proliferator-activated receptor-gamma (PPAR
      gamma), such as rosiglitazone, have been recently demonstrated to regulate
      inflammation by modulating the production of inflammatory mediators. The purpose
      of this study was to examine the effects of rosiglitazone on lipopolysaccharide
      (LPS)-induced kidney inflammation and to explore the mechanism of its
      renoprotection. METHODS: Mice were treated with LPS with or without pretreatment
      with rosiglitazone. Blood urea nitrogen (BUN), creatinine levels, the urinary
      albumin-to-creatinine ratio, macrophage infiltration, monocyte chemoattractant
      protein-1 (MCP-1) expression, PPAR-gamma expression, and NF-kappaB and PPAR-gamma
      activity were investigated. HK-2 cells were maintained under defined in vitro
      conditions, treated with either rosiglitazone and/or the PPAR-gamma antagonist
      GW9662, and then stimulated with LPS. MCP-1, IL-8, IL-6, NF-kappaB activity and
      PPAR-gamma expression were investigated. RESULTS: Compared to the LPS only group,
      pretreatment with rosiglitazone in vivo significantly attenuated the BUN levels
      macrophage infiltration, MCP-1 overexpression and NF-kappaB activity (p < 0.05).
      Rosiglitazone also restored PPAR-gamma expression and protein activity, which
      were reduced significantly in the LPS only group (p < 0.05). Furthermore, in the
      LPS-stimulated HK-2 cells, rosiglitazone downregulated MCP-1, IL-8 and IL-6
      expression as well as NF-kappaB activation and increased PPAR-gamma expression (p
      < 0.05). These effects were diminished by GW9662. CONCLUSION: These results
      showed that pretreatment with rosiglitazone could attenuate kidney inflammation
      through the activation of PPAR-gamma, suppression of MCP-1 overproduction and NF
      kappaB activation. Rosiglitazone had a protective effect via a PPAR-gamma
      dependent pathway in LPS-treated HK-2 cells.

PMID- 21734369
TI  - Thigh circumference as a useful predictor of body fat in adolescent girls with
      anorexia nervosa.
AB  - BACKGROUND/AIM: Girls with anorexia nervosa (AN) demonstrate severe depletion of
      body fat. The aim of this study was to determine an accurate anthropometric
      measurement for clinical assessment of fat depletion in girls with AN in
      connection with body composition measured by dual-energy X-ray absorptiometry
      (DXA). METHODS: In 64 female AN patients aged 12.8-23.1 years (mean 16.0 +/-
      1.8), body mass index (BMI), skinfold thickness (subscapular, abdominal and
      triceps), mid-upper arm and thigh circumference, fat mass (FM) and lean mass were
      determined and compared with the data of 71 controls. RESULTS: Girls with AN had
      lower anthropometric traits and were fat depleted compared to controls (14.9 +/-
      7.3 vs. 27.4 +/- 6.4% of FM using DXA; all p < 0.001). BMI, thigh circumference
      and subscapular skinfold thickness demonstrated a very similar predictive value
      for DXA assessment of body fat. Based on the receiver-operating characteristic
      curve analysis and the determination of the positive predictive value, thigh
      circumference appeared the most specific and sensitive anthropometric predictor
      of fatness discriminating between AN and healthy girls, with the AUC value
      reaching 0.95 (95% CI = 0.92-0.97). Using a cutoff value of 49.6 cm, accuracy was
      90.6%, sensitivity 93% and specificity 88.7%. CONCLUSIONS: Thigh circumference
      strongly correlates with DXA-FM and demonstrates a slight clinical advantage over
      BMI. This simple measurement might also serve as a useful predictor of body
      fatness in adolescent girls with AN and should therefore be further evaluated in
      independent cohort studies.

PMID- 21734372
TI  - Feasibility and safety of stenting for symptomatic carotid arterial dissection.
AB  - OBJECTIVE: To determine the procedural feasibility and safety of carotid
      angioplasty and stent placement of carotid artery dissection (CAD) patients who
      had failed antithrombotic therapy in acute dissection. METHODS: A series of 33
      consecutive patients (mean age, 40.21 years; 29 men and 4 women) who underwent
      angioplasty and stent placement for symptomatic carotid artery dissection (sCAD)
      from May 2005 to December 2010 in the Nanjing Stroke Registry Program (NSRP) was
      retrospectively reviewed. All the included patients had been diagnosed
      definitively based on catheter angiography, and had failed to respond to medical
      therapy during the course of initial hospital admission. The baseline and
      followed up data of these patients were collected and analyzed. RESULTS: Of all
      the 33 included patients, 32 patients had achieved technical success without any
      intraoperative complications. Two patients manifested ipsilateral Horner sign on
      the next day after stenting, and one of them suffered from recurrence of
      transient ischaemic attack (TIA) during the course of follow up, but completely
      remission via antithrombotic therapy. CONCLUSION: Endovascular stenting is a
      feasible and safe therapeutic strategy of CAD patients who have failed medical
      therapy.

PMID- 21734373
TI  - Relationship between pulse wave velocity and carotid atherosclerosis in geriatric
      people.
AB  - OBJECTIVE: To investigate the relationship between the pulse wave velocity (PWV)
      and angiographic carotid atherosclerosis in elderly patients. METHOD: 103
      consecutive elderly patients were divided into two groups according to the
      results of cerebral angiography: carotid atherosclerosis group and normal carotid
      angiogram group. Basic clinical information was required by a standardized
      questionnaire. Carotid-femoral PWV (cfPWV) as a marker of Stiffness of artery was
      measured, Carotid intima media thickness (IMT) and carotid stenosis degree in
      angiography was evaluated. Independent-sample t test was used to evaluate the
      difference in cfPWV between the two groups, Bivariate associations between cfPWV
      and an index of extracoronary atherosclerosis (IMT and severity of stenosis) was
      performed. RESULT: Among 103 subjects, 55 with carotid atherosclerosis and 48
      with a normal carotid angiogram, a significant difference between the two groups
      in IMT and PWV was found (P<0.05), and the cfPWV was significantly correlated
      with IMT (r = 0.3222, P = 0.0315), but not severity of carotid stenosis (r =
      0.1573, P = 0.3137). CONCLUSION: cfPWV showed a positive correlation to carotid
      IMT, and maybe is a potentially useful adjunctive atherosclerotic risk marker to
      Identify of early carotid atherosclerosis.

PMID- 21734374
TI  - Aldosterone pathway in atrial fibrillation.

PMID- 21734375
TI  - Increased plasma aldosterone during atrial fibrillation declines following
      cardioversion.
AB  - OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) may be activated
      during atrial fibrillation (AF); our aim was to evaluate the level of aldosterone
      in patients with either permanent AF, persistent AF scheduled for cardioversion
      or patients in sinus rhythm (SR). We hypothesized that an increased level of
      aldosterone is found in patients with AF, decreasing in patients with restored
      SR. METHODS: The study included 60 patients with persistent AF scheduled for
      elective cardioversion, 19 patients with permanent AF, and a control group of 19
      healthy individuals. All patients were examined and their aldosterone levels were
      measured. Measurement of aldosterone was repeated at follow-up 1, 30 and 180 days
      after successful cardioversion was achieved. Statistical analysis was conducted
      using the Kruskal-Wallis rank sum test and the paired t test. RESULTS: At follow
      up, 1, 30, and 180 days after successful cardioversion of the patients with
      persistent AF, data showed that 49, 27, and 21 patients, respectively, were still
      in SR. At baseline, median values of plasma aldosterone in the healthy controls,
      the patients with persistent AF and those with permanent AF were 52, 68, and 80
      pg/ml, respectively. The log aldosterone in patients with persistent AF was
      significantly increased when compared to the control group (p = 0.026). No effect
      of age and gender was observed. The level of aldosterone decreased over time in
      patients with AF undergoing cardioversion and maintaining SR, both at a follow-up
      of 30 days (p = 0.0032) and 180 days (p = 0.037). CONCLUSIONS: Patients with AF
      had a raised aldosterone level compared to the healthy control individuals.
      Restoration and maintenance of SR in patients with persistent AF significantly
      lowered the level of aldosterone up to 180 days after cardioversion, indicating
      activation of RAAS during AF.

PMID- 21734376
TI  - Epigenetics: principles and practice.
AB  - Epigenetics is defined as heritable changes in gene expression that are, unlike
      mutations, not attributable to alterations in the sequence of DNA. The
      predominant epigenetic mechanisms are DNA methylation, modifications to
      chromatin, loss of imprinting and non-coding RNA. Epigenetic regulation of gene
      expression appears to have long-term effects and wide-ranging effects on health.
      Diet and environmental exposures may potentially alter the level and scope of
      epigenetic regulation, thus interesting developments in the study of epigenetics
      might explain correlations that researchers have found between lifestyle and risk
      of disease. Aberrant epigenetic patterns have been linked to a number of
      digestive diseases including Barrett's esophagus, cirrhosis, inflammatory bowel
      disease, and numerous gastrointestinal malignancies. In fact, many exciting
      discoveries about epigenetics in general have been made by studying diseases of
      the gastrointestinal tract and hepatobiliary tree. Epigenetic modifications of
      DNA in cancer and precancerous lesions offer hope and the promise of novel
      biomarkers for early cancer detection, prediction, prognosis, and response to
      treatment. Furthermore, reversal of epigenetic changes represents a potential
      target of novel therapeutic strategies and medication design. In the future, it
      is anticipated that innovative diagnostic tests, treatment regimens, and even
      lifestyle modifications will be based on epigenetic mechanisms and be
      incorporated into the practice of medicine.

PMID- 21734377
TI  - Interaction between susceptibility and environment: examples from the digestive
      tract.
AB  - During the last few years a significant advance has been achieved in the
      understanding of the pathogenesis of inflammatory bowel disease (IBD). From twin
      studies it was evident that there is more that 50% concordance of Crohn's disease
      (CD) in monozygotic twin pairs, however it is only 3.6% among dizygotic twins.
      These data indicate that the genetic background may be responsible for 50% of the
      risk or 'susceptibility' to develop CD. Obviously it is not a sufficient
      condition as otherwise there would be 100% concordance of disease in monozygotic
      twin pairs. Environmental factors as well must play an important role. This is
      further supported by the fact that there is only low development in genetic risk
      factors over ten thousands of years. In contrast, the incidence of CD and
      ulcerative colitis (UC) has dramatically increased in Western countries in the
      last 100 years. This further supports the concept of a 'Western lifestyle
      factor(s)' that triggers chronic intestinal inflammation in a genetically
      susceptible host. The proof of the concept of a genetic susceptibility was
      achieved in 2001 with the discovery that NOD2 is the most important
      susceptibility gene for CD. The function of NOD2 has been investigated in detail.
      NOD2 is an intracellular 'alarm button', a receptor recognizing invading bacteria
      that entered the mucosal wall. NOD2 mutants associated with susceptibility to CD
      seem to be deficient in their recognition of bacterial wall products. In a genome
      wide association study a disease association was found in the autophagy-related
      16-like 1 gene (ATG16L1). The ATG16L1 gene encodes a protein in the autophagosome
      pathway that processes intracellular bacteria. Based on these findings, CD is now
      discussed as an impaired and inadequate immune reaction to the gut bacteria which
      are a part of our environment (or perhaps 'in-vironment'). In addition to NOD2
      and ATG16L1, there are more 'innate' pathways by which commensal and pathogenic
      bacteria can directly interact with cells of the intestinal mucosa. The
      'environment concept' and the 'genetic concept' of IBD pathophysiology are
      converging. With the finding that most susceptibility genes for CD and UC are
      involved in innate immune mechanisms and the primary defense against bacteria
      entering the mucosa, for the first time a unifying concept of the 'genetic
      pathophysiology hypothesis' and the 'environment pathophysiology hypothesis' of
      IBD was possible. Bacteria are the link between the environment and mucosal
      defense system.

PMID- 21734378
TI  - Hygiene and other early childhood influences on the subsequent function of the
      immune system.
AB  - The current 'Darwinian' synthesis of the hygiene (or 'Old Friends') hypothesis
      suggests that the increase in chronic inflammatory disorders that started in
      Europe in the mid-19th century and progressed until the late 20th century is at
      least partly attributable to immunodysregulation resulting from lack of exposure
      to microorganisms that were tasked by co-evolutionary processes with establishing
      the 'normal' background levels of immunoregulation, a role that they perform in
      concert with the normal microbiota. This is an example of 'evolved dependence'.
      The relevant organisms co-evolved with mammals, already accompanied early
      hominids in the Paleolithic era and are associated with animals, mud and faeces.
      These organisms often establish stable carrier states, or are encountered
      continuously in primitive environments as 'pseudocommensals' from mud and water.
      These organisms were not lost during the first epidemiological transition, which
      might even have resulted in increased exposure to them. However, the crucial
      organisms are lost progressively as populations undergo the second
      epidemiological transition (modern urban environment). Recently evolved sporadic
      'childhood infections' are not likely to have evolved immunoregulatory roles, and
      epidemiology supports this contention. The consequences of the loss of the Old
      Friends and distortion of the microbiota are aggravated by other modern
      environmental changes that also lead to enhanced inflammatory responses (obesity,
      vitamin D deficiency, pollution (dioxins), etc.). The range of chronic
      inflammatory disorders affected may be larger than had been assumed (allergies,
      autoimmunity, inflammatory bowel disease, but also coeliac disease, food allergy,
      vascular disease, some cancers, and depression/anxiety when accompanied by raised
      inflammatory cytokines).

PMID- 21734379
TI  - Nutritional influences in selected gastrointestinal diseases.
AB  - Nutritional factors, as sources of luminal antigens, have been thought to be
      important factors in the immunopathogenesis of numerous gastrointestinal
      diseases. In some diseases, the role of the nutritional component is causal in
      the susceptible host. Such diseases include celiac disease, a common heritable
      chronic inflammatory condition of the small intestine induced by dietary wheat,
      rye and barley, in susceptible individuals. Specific HLA-DQ2 and HLA-DQ8 risk
      alleles are necessary, but not sufficient, for disease development. The well
      defined role of HLA-DQ heterodimers encoded by these alleles is to present cereal
      peptides to CD4+ T cells, activating an inflammatory immune response in the
      intestine. Genome-wide association studies have been performed which identified
      the IL2-IL21 risk locus and other genes with immune functions and key roles in
      thymic T-cell selection. Another example for this group is Wilson's disease, an
      autosomal recessive disorder of copper metabolism caused by mutation of the ATP7B
      gene, resulting in a defect of biliary copper excretion and toxic accumulation in
      the body, especially in the liver, brain and cornea, resulting in hepatic and/or
      neurological symptoms. In other diseases, however, the association is less well
      established. In such endeavor, epidemiological observations may become a valuable
      part of the overall investigations aimed at identifying dietary factors, which
      are involved in the initiation and perpetuation of the specific disease. As an
      example, relationships between nutrition and colorectal cancer have been
      hypothesized early on (e.g. folate, calcium, vitamin D, red meat). Similarly,
      intake of certain diet constituents like fat, refined sugar, fruits, vegetables
      and fiber was reported to be associated with the expression of inflammatory bowel
      diseases. In addition, in children with active Crohn's disease, enteral nutrition
      was found to be equally effective as corticosteroids in induction of remission,
      with mucosal healing induced by downregulation of mucosal pro-inflammatory
      cytokine profiles in both the ileum and the colon after enteral nutrition.
      However, the particular effect of the consumption of each type of food remains
      questionable in most cases, at least in part because of insufficient data and
      serious methodological limitations (e.g. recall bias, heterogeneity between
      collected data, lack of correction for covariates, difficulties in double
      blinding).

PMID- 21734380
TI  - Bacteria as trigger for chronic gastrointestinal disorders.
AB  - Apart from acute infections, microorganisms may also induce or perpetuate chronic
      inflammatory diseases and reversible or irreversible proliferation of various
      cells in the gastrointestinal tract (the extreme being adenocarcinoma and
      lymphoma). Helicobacter pylori is not only involved in the pathogenesis of
      lymphoma and gastric adenocarcinoma. The steps and mechanisms of the carcinogenic
      process involve host predisposition, environmental factors, and strain virulence.
      The steps of lymphoma genesis include chronic inflammation, acquisition of mucosa
      associated lymphoid tissue in the stomach, proliferation of the B lymphocytes in
      an inflammatory context, acquisition of genetic anomalies and dysregulation of
      the NF-kappaB pathway. The role of Campylobacter jejuni in immunoproliferative
      small bowel disease has also been shown and eradication of this bacterium can
      cure the lymphoma at its early stage. The evidence for the role of some bacteria
      in colon cancer development is discussed. Opportunistic pathogens are detected in
      the stools or mucosa of a proportion of subjects with Crohn's disease. They
      include Mycobacterium avium paratuberculosis, adherent invasive Escherichia coli,
      and Clostridium difficile. A dysbiosis has been repeatedly observed in patients
      with inflammatory bowel disease. Instability of the dominant microbiota and
      decreased biodiversity (especially in the firmicutes phylum) are major
      characteristics. The decrease of Faecalibacterium prausnitzii seems to have a
      prognostic value to predict relapse of Crohn's disease after surgery. Finally,
      important perspectives are opened by new tools such as metagenomics and
      metabolomics of the gastrointestinal ecosystems. Major tracks concern irritable
      bowel syndrome, colon cancer and obesity.

PMID- 21734381
TI  - Mechanisms of drug toxicity or intolerance.
AB  - Classically, adverse drug reactions had been considered as type A reactions which
      are related to the main pharmacological action of the drug and therefore are
      predictable. Such reactions are predictable, reversible, and usually can be
      managed by lowering the dose of the offending drug. However, other adverse
      effects of drugs can occur which are unrelated to the main pharmacological action
      of the drug - type B reactions. Such adverse effects are termed idiosyncratic and
      are often initiated by metabolites of the parent drug or by other indirect
      mechanisms. The detailed understanding of adverse drug events has become a major
      focus of the regulatory agencies throughout the world. The pharmacotherapy of
      gastrointestinal and liver disorders is becoming increasingly complex. In recent
      years, with the advent of novel therapeutic agents to treat a host of disorders,
      including viral hepatitis, gastrointestinal motility disorders, inflammatory
      bowel disease and others, the potential for serious clinically relevant drug
      reactions has increased. In the pharmacotherapy of gastrointestinal and liver
      diseases, a significant number of adverse events that occur can be explained by
      drug interactions. Some pharmacokinetic drug interactions are based on the
      competitive inhibition of the rate of drug metabolism of one of the drugs,
      leading to an increased concentration of the drug which was not intended. In
      other examples, the interaction can be mechanistic in which one or more drugs
      when co-administered potentiate each other's actions without any change in drug
      levels, termed pharmacodynamic interactions.

PMID- 21734382
TI  - Alcohol and smoking.
AB  - The WHO ranks smoking and alcohol consumption as the first and third leading
      causes of the global burden of disease in industrialized countries, using
      disability-adjusted life years (DALYs) as a combined measure of premature death
      and disability. Smoking is responsible for 12.2% of all DALYs and alcohol
      consumption for 9.2%. For example in Germany, annually 110,000-140,000 humans die
      prematurely because of cigarette smoking and 40,000 because of alcohol drinking.
      In Europe and the USA, more than 20% of all hospitalized men and more than 9% of
      all hospitalized women suffer from alcohol-associated diseases. In Germany, about
      2.0 million people in the age group 18-64 years (3.8% of all Germans) are alcohol
      abusers and 1.3 million people (2.4%) are alcohol-dependent. Alcohol can cause
      acute as well as chronic damage in nearly all body organs. Smoking damages also
      nearly every human body organ and is worldwide the most important single
      preventable health risk factor as well as the main cause for premature mortality
      in industrial countries. One third of the adult Germans as well as of the world
      population are active smokers; men smoke more frequently than women (34.0 vs.
      25.1%). In this review a short overview will be given on the most important
      deleterious effects of alcohol and smoking. The most recent data about the
      pathophysiological relevance of non-alcoholic compounds of alcoholic beverages
      will also be discussed.

PMID- 21734383
TI  - Infections and the liver.
AB  - BACKGROUND: Hepatitis B (HBV) and hepatitis C virus (HCV) have infected nearly
      half a billion individuals worldwide and are major indications for liver
      transplantation. Key requirements to successful outcomes with modern antiviral
      drugs are favourable host factors. RESULTS: Single nucleotide polymorphisms near
      the IL28B gene location which encode for interferon (IFN)-lambda3 have a large
      effect in determining the likelihood of patients obtaining a cure from pegylated
      IFN-alpha and ribavirin combination therapy or spontaneous clearance of the HCV.
      80% of patients who carry two copies of this advantageous variant cleared the
      virus during IFN therapy and remained virus-free with a sustained viral response.
      This mutation is more common in Caucasian and Asian populations, whereas it is
      only found in the 40-50% of sub-Saharan Africans who are known to be more
      resistant to combination therapy. Similarly, host factors control tolerance to
      chronic HBV infection and can fluctuate over time with increased risk of
      progression to cirrhosis and particularly liver cancer. Loss of viral tolerance
      with reactivation and hepatitis is increasingly seen with the widespread use of
      biological treatments for diseases such as inflammatory bowel disease or
      rheumatoid arthritis. Natural disasters and conflicts in some parts of the world
      have also seen an increase in cases of hepatitis A and E virus infection and
      highlighted the global public health burden from viral-induced hepatitis.
      CONCLUSIONS: Increased appreciation of the interaction between host factors and
      the viral life cycles is likely to significantly alter the way we target these
      infections in the future.

PMID- 21734384
TI  - Gallstones: environment, lifestyle and genes.
AB  - Gallstone disease represents one of the most common and costly
      gastroenterological disorders. In Germany, 0.25% of the population undergo
      cholecystectomy per year, and cholelithiasis incurs annual medical expenses of
      more than USD 6.5 billion in the United States. The paradigm of environmental
      risk factors for gallstones has lately been challenged by genetic studies in
      experimental models and humans. The analysis of more than 40,000 Swedish twin
      pairs with gallstones demonstrated that genetic factors account for 25% of the
      phenotypic variance. Since then, studies employing genome-wide association
      analysis, case-control cohorts and analysis of sib-pairs in families with
      gallstones have expanded our knowledge of 'gallstone genes'. Indeed, gallstone
      disease phenotypes are likely to result from the complex interaction of genetic
      factors, chronic overnutrition with carbohydrates, depletion of dietary fibre and
      other not fully defined environmental factors including physical inactivity and
      infections. This hypothesis is supported by the profound increases of cholesterol
      gallstone prevalence rates in Native Americans, post-war European countries and
      current urban centres in East Asia, all of which were associated with
      'westernized' nutrition. Herein, we summarise the spectrum of environmental and
      genetic risk factors which should pave the way to 'personalised' strategies for
      the prevention and therapy of gallstones.

PMID- 21734385
TI  - ASH and NASH.
AB  - Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) have a
      similar pathogenesis and histopathology but a different etiology and
      epidemiology. NASH and ASH are advanced stages of non-alcoholic fatty liver
      disease (NAFLD) and alcoholic fatty liver disease (AFLD). NAFLD is characterized
      by excessive fat accumulation in the liver (steatosis), without any other evident
      causes of chronic liver diseases (viral, autoimmune, genetic, etc.), and with an
      alcohol consumption <=20-30 g/day. On the contrary, AFLD is defined as the
      presence of steatosis and alcohol consumption >20-30 g/day. The most common
      phenotypic manifestations of primary NAFLD/NASH are overweight/obesity, visceral
      adiposity, type 2 diabetes, hypertriglyceridemia and hypertension. The prevalence
      of NAFLD in the general population in Western countries is estimated to be 25
      30%. The prevalence and incidence of NASH and ASH are not known because of the
      impossibility of performing liver biopsy in the general population. Up to 90% of
      alcoholics have fatty liver, and 5-15% of these subjects will develop cirrhosis
      over 20 years. The risk of cirrhosis increases to 30-40% in those who continue to
      drink alcohol. About 10-35% of alcoholics exhibit changes on liver biopsy
      consistent with alcoholic hepatitis. Natural histories of NASH and ASH are not
      completely defined, even if patients with NASH have a reduced life expectancy due
      to liver-related death and cardiovascular diseases. The best treatment of
      AFLD/ASH is to stop drinking, and the most effective first-line therapeutic
      option for NAFLD/NASH is non-pharmacologic lifestyle interventions through a
      multidisciplinary approach including weight loss, dietary changes, physical
      exercise, and cognitive-behavior therapy.

PMID- 21734386
TI  - From aphthous ulcer to full-blown Crohn's disease.
AB  - At onset, Crohn's disease (CD) is characterized by transmural inflammation with
      mucosal ulcerations. In its earliest phase the lesions are mainly aphthous
      ulcers. The ulcers then become larger, a nodular pattern develops and penetration
      of the deep ulcers leads to fistulas and collagen deposition to fibrotic
      strictures. The best model to study the earliest lesions in CD is the
      postoperative recurrence situation where these early lesions recur within weeks
      to months after surgery. CD recurrence is triggered by the fecal contents of the
      gut since temporary diversion prevents the recurrence of bowel inflammation. With
      the development of newer techniques, such as microarray analysis of total mucosal
      gene expression and molecular analysis of gut content and mucosal microbiome,
      this model will allow to shed light on the earliest pathogenic features of CD.

PMID- 21734387
TI  - Irritable bowel syndrome: gender, infection, lifestyle or what else?
AB  - Irritable bowel syndrome (IBS) is characterised by abdominal pain and an erratic
      bowel habit, which depending on the definition used affects 5-10% of the
      population. As a typical complex disease, it is likely that the condition will
      develop when a genetically susceptible individual is exposed to an appropriate
      environment stimulus. This bio-psycho-social model assumes that there is no one
      cause of IBS, but rather that it is the product of complex interactions between
      host and environment. Host factors include gender, age and psychological
      characteristics, while environmental factors include psychosocial stressors,
      gastrointestinal infections, antibiotics and food.

PMID- 21734388
TI  - Colon cancer: a civilization disorder.
AB  - Colorectal cancer arises in individuals with acquired or inherited genetic
      predisposition who are exposed to a range of risk factors. Many of these risk
      factors are associated with affluent Western societies. More than 95% of
      colorectal cancers are sporadic, arising in individuals without a significant
      hereditary risk. Geographic variation in the incidence of colorectal cancer is
      considerable with a higher incidence observed in the West. Environmental factors
      contribute substantially to this variation. A number of these risk factors are
      associated with a Western lifestyle and could be considered a product of
      'civilization'. Recently, smoking has been recognized as a risk factor. Energy
      consumption also influences colorectal cancer risk, with obesity increasing risk
      and exercise reducing risk. However, the strongest contribution to environmental
      risk for colorectal cancer is dietary. Consumption of fat, alcohol and red meat
      is associated with an increased risk. Fresh fruit and vegetables and dietary
      fibre may be protective. Much has been learnt recently about the molecular
      pathogenesis of colorectal cancer. Colorectal cancer always arises in the context
      of genomic instability. There is inactivation of the tumour suppressor genes
      adenomatous polyposis coli, p53, transforming growth factor-beta, activation of
      oncogene pathways including K-ras, and activation of the cyclooxygenase-2,
      epidermal growth factor receptor and vascular endothelial growth factor pathways.
      The mechanisms by which some environmental factors modify the mutation risk in
      these pathways have been described.

PMID- 21734389
TI  - Effects of environment and lifestyle on gastroesophageal reflux disease.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is comprised of a spectrum of
      related disorders, including hiatal hernia, reflux disease with its associated
      symptoms, erosive esophagitis, peptic stricture, Barrett's esophagus, and
      esophageal adenocarcinoma. Besides multiple pathophysiological associations among
      these disorders, they are also characterized by their comorbid occurrence in
      identical patients and by their similar epidemiologic behavior. The occurrence of
      GERD is shaped by marked temporal and geographic variations, suggesting the
      influence of environmental risk factors in the etiology of these diseases.
      VARIATIONS BY TIME, GEOGRAPHY, AND RACE: Between 1975 and 2005, the incidence of
      GERD and esophageal adenocarcinoma increased fivefold in most Western countries.
      The incidence of GERD also appears to be rising in the most developed countries
      of Asia. All severe forms of GERD, such as erosive esophagitis, peptic stricture,
      Barrett's metaplasia, and esophageal adenocarcinoma, are more common among whites
      than other ethnic groups. AFFLUENCE AND OBESITY AS RISK FACTORS: Barrett's
      esophagus and esophageal adenocarcinoma tend to occur slightly more often in
      subjects with higher income. Overweight and obesity contribute to the development
      of hiatal hernia, increase intra-abdominal pressure, and promote gastroesophageal
      reflux. Weight gain increases reflux symptoms, whereas weight loss decreases such
      symptoms. Other risk factors, such as smoking, alcohol, dietary fat, or drugs,
      play only a minor role in shaping the epidemiologic patterns of GERD. PROTECTION
      THROUGH HELICOBACTER PYLORI: On a population level, a high prevalence of H.
      pylori infection is likely to reduce levels of acid secretion and protect some
      carriers of the infection against reflux disease and its associated
      complications. Several studies have confirmed a lesser prevalence of H. pylori
      among subjects with than without GERD. Until recently, populations in Africa and
      Asia may have been protected against the development of GERD and esophageal
      adenocarcinoma by their higher prevalence of H. pylori infection. CONCLUSION: The
      study of environmental risk factors may provide an opportunity to better
      understand GERD and develop a means of its prevention.

PMID- 21734390
TI  - Environmental risk factors for chronic pancreatitis and pancreatic cancer.
AB  - Chronic pancreatitis has long been thought to be mainly associated with
      immoderate alcohol consumption. The observation that only ~10% of heavy drinkers
      develop chronic pancreatitis not only suggests that other environmental factors,
      such as tobacco smoke, are potent additional risk factors, but also that the
      genetic component of pancreatitis is more common than previously presumed. Either
      disease-causing or protective traits have been indentified for mutations in
      different trypsinogen genes, the gene for the trypsin inhibitor SPINK1,
      chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator
      (CFTR). Other factors that have been proposed to contribute to pancreatitis are
      obesity, diets high in animal protein and fat, as well as antioxidant
      deficiencies. For the development of pancreatic cancer, preexisting chronic
      pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The
      data on environmental risk factors for pancreatic cancer are, with the notable
      exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity
      appears to increase the risk of pancreatic cancer in the West but not in Japan.
      Diets high in processed or red meat, diets low in fruits and vegetables,
      phytochemicals such as lycopene and flavonols, have been proposed and refuted as
      risk or protective factors in different trials. The best established and single
      most important risk factor for cancer as well as pancreatitis and the one to
      clearly avoid is tobacco smoke.

PMID- 21734391
TI  - Pathophysiology of non-alcoholic steatohepatitis and basis for treatment.
AB  - Non-alcoholic fatty liver disease (NAFLD) is likely the most common cause of
      liver disease in adults as well as in children and adolescents. Its occurrence is
      closely associated with obesity and insulin resistance. NAFLD may lead to non
      alcoholic steatohepatitis (NASH) with possible evolution towards cirrhosis and
      hepatocellular carcinoma. In addition to steatosis, NASH is characterized by
      necroinflammation and fibrosis. While the presence of simple steatosis can be
      assessed by imaging studies, the occurrence of NASH and its staging requires a
      liver biopsy. Along these lines, major efforts are directed at identifying non
      invasive methodologies able to discriminate simple NAFLD from NASH and to predict
      the stage of fibrotic evolution. Current treatment relies on weight loss and
      exercise, although various insulin-sensitizing agents, antioxidants and anti
      inflammatory and antifibrogenic agents are under evaluation.

PMID- 21734392
TI  - Environmental and lifestyle influences on disorders of the large and small
      intestine: implications for treatment.
AB  - There is growing evidence that many aspects of our lifestyle and the environment
      we now live in contribute to the development of disease. The luminal digestive
      tract is a clear target of the influence of dietary components, alcohol,
      microbial organisms, and other ingested materials. External factors including
      obesity, lack of physical exercise, and tobacco consumption also impact diseases
      of the luminal gastrointestinal (GI) tract. A growing understanding of the
      microbiome which forms an integral part of the human organism indicates that this
      is another important external force that impacts human health and disease. The
      luminal GI tract conditions that arise, at least in part, from these external
      factors range from malignancies (squamous cell esophageal cancer, Barrett's
      esophagus and associated esophageal adenocarcinoma, gastric cancer, and
      colorectal cancer), idiopathic inflammatory disorders such as inflammatory bowel
      diseases, and post-infectious syndromes including post-infectious irritable bowel
      syndrome, post-infectious dyspepsia and other functional GI disorders. Of
      particular interest, given their increase in prevalence in much of the world, are
      immune-mediated conditions in which food antigens are the driving force behind
      disease development. These entities include celiac disease, eosinophilic
      esophagitis, and food allergies. Celiac disease is a prime example of a condition
      mediated by dietary factors whose pathogenesis has only recently been determined,
      providing opportunities for developing treatment options beyond the gluten-free
      diet. While a genetic basis for this disease clearly exists, it is believed that
      environmental factors such as an increase in gluten in the human diet account for
      its rising prevalence, now roughly 1% of genetically susceptible populations in
      all continents. Proposed therapeutic strategies span from preventing disease by
      modulating the time of gluten introduction in infants, to reducing exposure to
      gluten by developing strains of wheat with lower levels of gluten, degrading
      ingested gluten peptides within the intestinal lumen via endopeptidases or
      modulating uptake of these peptides across intestinal tight junctions. Other
      novel treatments in development focus on interfering with the immune events that
      lead to disease once gluten accesses the lamina propria including altering the
      immune milieu from a Th1-predominant response via hookworm infection, inhibiting
      tissue transglutaminase, and blocking antigen presentation and/or T-cell
      responses to gluten peptides. While new treatment options for celiac disease
      reflect the complex interaction of diet, genetic factors and the host immune
      response, the implications for treatment of many conditions of the large and
      small intestine that arise from environmental and lifestyle are as basic as
      ensuring adequate nutrition, regular exercise and cessation of tobacco use. Much
      more needs to be learned about the microbiome, dietary and other factors and
      their interaction with the human host in order to develop potential new treatment
      strategies for diseases that result from the environment and lifestyle.

PMID- 21734393
TI  - Diseases of the digestive tract: is prevention possible and feasible?
AB  - Prevention is and will remain a major goal of medicine and gastroenterology.
      Economics will have a major influence. Preventive approaches will need to prove a
      favorable cost-benefit ratio before they are authorized for broad implementation.
      Personalized medicine is just starting, but undoubtedly it will accelerate, gain
      relevance and become an integral part of our clinical practice. Physicians in
      general and gastroenterologists specifically will need to seriously contemplate
      retraining/refocusing to gain competence in genetic/proteomic evaluation of
      individuals, or risk a significant degree of obsolescence.

PMID- 21734395
TI  - Neuropsychological correlates of the proportional impact of white matter
      hyperintensities on mild to moderate dementia: the MRI 300 study.
AB  - BACKGROUND: White matter hyperintensities (WMH) increase cognitive impairment in
      patients with dementia. OBJECTIVE: We investigated the impact of WMH on the
      neuropsychological profiles in patients with mild to moderate dementia. METHODS:
      We consecutively recruited newly diagnosed patients with mild to moderate
      dementia across South Korea for 1 year. The participants completed
      neuropsychological tests, magnetic resonance imaging, and structured neurological
      evaluations. The patients were divided into 3 categories, i.e. minimal, moderate,
      and severe WMH groups, according to the proportional degree of WMH. RESULTS: 289
      patients were recruited; 140 (48.3%) for the minimal WMH group, 99 (34.2%) for
      the moderate group, and 50 (17.5%) for the severe group. Both advanced age and
      low general cognitive level were significant contributors to WMH in patients with
      dementia. After adjusting for age, the neuropsychological correlates of the
      proportional impact of WMH were frontal executive, language, and attention
      profiles. However, the only significant neuropsychological correlate was the
      recognition memory profile after adjusting for both age and general cognitive
      level simultaneously. CONCLUSION: The results suggest that the most significant
      neuropsychological profile impacting the burden of WMH in patients with mild to
      moderate dementia was the recognition memory profile, regardless of age and
      general cognitive function.

PMID- 21734396
TI  - Subjective evaluation of voice and working conditions and phoniatric examination
      in kindergarten teachers.
AB  - AIMS: This study evaluated the prevalence of voice problems in kindergarten
      teachers and investigated some background factors affecting vocal health.
      METHODS: One hundred and nineteen female kindergarten teachers volunteered by
      responding to an Internet questionnaire on voice habits, voice symptoms, and the
      amount of negative impact various working conditions may have on their voices.
      Phoniatric examination was carried out with a rigid laryngoscope. RESULTS: Of the
      subjects, 71.5% reported frequent strain on the voice (monthly or more often),
      and 56.3% reported hoarseness without infection. Eighty-six percent reported that
      when their voice got tired during the working day it recovered quite well, well
      or remarkably well by the next day. Noise at work was considered most detrimental
      to the voice. Clear organic findings were observed in 10.9% of the cases and did
      not correlate with subjective voice symptoms. CONCLUSIONS: The results confirmed
      earlier findings that a remarkable number of kindergarten teachers suffer from
      voice problems and consider noise in the environment especially to be harmful to
      their voices. However, the majority reported recovering well from vocal symptoms.
      Further studies are needed on individual speech habits, working day-related voice
      evaluation, recovery time and work-environmental factors. A follow-up is
      warranted to identify the main factors leading to voice problems.

PMID- 21734397
TI  - The French version of Speech Handicap Index: validation and comparison with the
      Voice Handicap Index.
AB  - OBJECTIVE: This study aimed to adapt the Speech Handicap Index (SHI) in French,
      to compare it with the Voice Handicap Index (VHI) and to study its relevance in
      dysarthric patients. PATIENTS AND METHODS: Two hundred and twenty-nine subjects
      filled out the French versions of the SHI and VHI. SHI test-retest reliability
      was performed on 82 subjects. Psychometric properties were analyzed in 112
      healthy controls and 89 patients with speech disorders. Mean scores of 89 speech
      disordered and 28 dysphonic patients were obtained. RESULTS: For SHI, internal
      consistency (Cronbach's alpha >0.9) and test-retest reliability (Spearman's r >
      0.75) were high. Mean scores were significantly different between healthy
      subjects (8/120) and patients (52/120) (p < 0.0001). Scores were statistically
      different between dysphonic (40/120) and speech-disordered patients (52/120) (p <
      0.05), and also between patients with oropharyngeal surgery (44/120) and
      dysarthric patients (57/120) (p < 0.05). Patients with speech difficulties had
      higher scores on the SHI than dysphonic patients (p < 0.05). CONCLUSION: The
      French SHI is a reliable and sensitive tool. It can be proposed to all patients
      with speech disorders. The contrasting results between the SHI and the VHI
      highlight the importance in giving the appropriate questionnaire tailored to the
      patient's pathology.

PMID- 21734399
TI  - The structure of genetic linkage data: from LIPED to 1M SNPs.
AB  - There are three assumptions of independence or conditional independence that
      underlie linkage likelihood computations on sets of related individuals. The
      first is the independence of meioses, which gives rise to the conditional
      independence of haplotypes carried by offspring, given those of their parents.
      The second derives from the assumption of absence of genetic interference, which
      gives rise to the conditional independence of inheritance vectors, given the
      inheritance vector at an intermediate location. The third is the assumption of
      independence of allelic types, at the population level, both among haplotypes of
      unrelated individuals and also over the loci along a given haplotype. These three
      assumptions have been integral to likelihood computations since the first lod
      scores were computed, and remain key components in analysis of modern genetic
      data. In this paper we trace the role of these assumptions through the history of
      linkage likelihood computation, through to a new framework of genetic linkage
      analysis in the era of dense genomic marker data.

PMID- 21734400
TI  - Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50
      as associated with childhood atopic asthma.
AB  - OBJECTIVES: Asthma is a childhood disease that is strongly influenced by genetic
      factors. We sought to replicate an association between single nucleotide
      polymorphisms (SNPs) of the top-ranked candidate genes and childhood atopic
      asthma in Perinatal Risk of Asthma in Infants of Asthmatic Mothers (PRAM) study
      subjects. METHODS: Using data from a systematic literature search and an
      exploratory genome-wide association study conducted in a subset of the PRAM
      cohort, we followed a strict procedure to generate a ranked list of candidate
      genes. SNPs in the top 50 genes were genotyped in the full PRAM cohort (n = 103
      cases with doc- tor-diagnosed atopic asthma at age 6, and n = 499 controls).
      RESULTS: The literature search identified 251 prior risk genes from 469
      publications. RAD50 (rs2706347) and PTPRE (rs10830196) revealed crude
      associations with asthma at a Bonferroni-corrected level of significance (p <
      0.0011). IL4R (rs1801275), CCL5 (rs2280788), and TBXA2R (rs4523) revealed nominal
      significance (p < 0.05). When adjusted for race and gender, only rs2706347 in
      RAD50 remained significantly associated with asthma. SNPs in frequently
      replicated asthma risk genes, including TNF, IL13, ADAM33, TGFB1, and MS4A2,
      revealed no association. CONCLUSION: RAD50 may be a promising candidate asthma
      risk gene. Lack of evidence of highly reported polymorphisms in the present study
      highlights the genetic heterogeneity of asthma and emphasizes the need for robust
      replication of candidate genes.

PMID- 21734401
TI  - Novel autosomal recessive nonsyndromic hearing impairment locus DFNB90 maps to
      7p22.1-p15.3.
AB  - A novel locus DFNB90 was mapped to 7p22.1-p15.3 by carrying out a genome scan in
      a multigenerational consanguineous family from Pakistan with autosomal recessive
      nonsyndromic hearing impairment (ARNSHI).DFNB90 is the eighth ARNSHI locus mapped
      to chromosome 7. A multipoint LOD score of 4.0 was obtained at a number of SNP
      marker loci spanning from rs1468996 (chromosome 7: 5.7 Mb) tors957960 (chromosome
      7: 18.8 Mb). The 3-unit support interval and the region of homozygosity for
      DFNB90 spans from markers rs1553960 (chromosome 7: 4.9 Mb) to rs206198
      (chromosome 7: 20.3 Mb). Candidate genes ACTB, BZW, OCM, MACC1, NXPH1, PRPS1L1,
      RAC1 and RPA3, which lie within the DFNB90 region, were sequenced and no
      potentially causal variants were identified.

PMID- 21734402
TI  - A new expectation-maximization statistical test for case-control association
      studies considering rare variants obtained by high-throughput sequencing.
AB  - Genome-wide association studies (GWAS) have been successful in identifying common
      genetic variation reproducibly associated with disease. However, most associated
      variants confer very small risk and after meta-analysis of large cohorts a large
      fraction of expected heritability still remains unexplained. A possible
      explanation is that rare variants currently undetected by GWAS with SNP arrays
      could contribute a large fraction of risk when present in cases. This concept has
      spurred great interest in exploring the role of rare variants in disease. As the
      cost of sequencing continue to plummet, it is becoming feasible to directly
      sequence case-control samples for testing disease association including rare
      variants. We have developed a test statistic that allows for association testing
      among cases and controls using data directly from sequencing reads. In addition,
      our method allows for random errors in reads. We determine the probability of a
      true genotype call based on the observed base pair reads using the expectation
      maximization algorithm. We apply the SumStat procedure to obtain a single
      statistic for a group of multiple rare variant loci. We document the validity of
      our method through simulations. Our results suggest that our statistic maintains
      the correct type I error rate, even in the presence of differential
      misclassification for sequence reads, and that it has good power under a number
      of scenarios. Finally, our SumStat results show power at least as good as the
      maximum single locus results.

PMID- 21734403
TI  - Coordinated conditional simulation with SLINK and SUP of many markers linked or
      associated to a trait in large pedigrees.
AB  - Simulation of genotypes in pedigrees is an important tool to evaluate the power
      of a linkage or an association study and to assess the empirical significance of
      results. SLINK is a widely-used package for pedigree simulations, but its
      implementation has not previously been described in a published paper. SLINK was
      initially derived from the LINKAGE programs. Over the 20 years since its release,
      SLINK has been modified to incorporate faster algorithms, notably from the
      linkage analysis package FASTLINK, also derived from LINKAGE. While SLINK can
      simulate genotypes on pedigrees of high complexity, one limitation of SLINK, as
      with most methods based on peeling algorithms to evaluate pedigree likelihoods,
      is the small number of linked markers that can be generated. The software package
      SUP includes an elegant wrapper for SLINK that circumvents the limitation on
      number of markers by using descent markers generated by SLINK to simulate a much
      larger number of markers on the same chromosome, linked and possibly associated
      with a trait locus. We have released new coordinated versions of SLINK (3.0;
      available from http://watson.hgen.pitt.edu) and SUP (v090804; available from
      http://mlemire.freeshell.org/software or http://watson.hgen.pitt.edu) that
      integrate the two software packages. Thereby, we have removed some of the
      previous limitations on the joint functionality of the programs, such as the
      number of founders in a pedigree. We review the history of SLINK and describe how
      SLINK and SUP are now coordinated to permit the simulation of large numbers of
      markers linked and possibly associated with a trait in large pedigrees.

PMID- 21734404
TI  - Genome-wide linkage analysis to identify genetic modifiers of ALK mutation
      penetrance in familial neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (NB) is an important childhood cancer with a strong
      genetic component related to disease susceptibility. Approximately 1% of NB cases
      have a positive family history. Following a genome-wide linkage analysis and
      sequencing of candidate genes in the critical region, we identified ALK as the
      major familial NB gene. Dominant mutations in ALK are found in more than 50% of
      familial NB cases. However, in the families used for the linkage study, only
      about 50% of carriers of ALK mutations are affected by NB. METHODS: To test
      whether genetic variation may explain the reduced penetrance of the disease
      phenotype, we analyzed genome-wide genotype data in ALK mutation-positive
      families using a model-based linkage approach with different liability classes
      for carriers and non-carriers of ALK mutations. RESULTS: The region with the
      highest LOD score was located at chromosome 2p23-p24 and included the ALK locus
      under models of dominant and recessive inheritance. CONCLUSIONS: This finding
      suggests that variants in the non-mutated ALK gene or another gene linked to it
      may affect penetrance of the ALK mutations and risk of developing NB in familial
      cases.

PMID- 21734405
TI  - Two-stage design of sequencing studies for testing association with rare
      variants.
AB  - Multiple rare variants have been suggested as accounting for some of the
      associations with common single nucleotide polymorphisms identified in genome
      wide association studies or possibly some of the as yet undiscovered
      heritability. We consider the power of various approaches to designing substudies
      aimed at using next-generation sequencing technologies to discover novel variants
      and to select some subsets that are possibly causal for genotyping in the
      original case-control study and testing for association using various weighted
      sum indices. We find that the selection of variants based on the statistical
      significance of the case-control difference in the subsample yields good power
      for testing rare variant indices in the main study, and that multivariate models
      including both the summary index of rare variants and the associated common
      single nucleotide polymorphisms can distinguish which is the causal factor. By
      simulation, we explore the effects of varying the size of the discovery
      subsample, choice of index, and true causal model.

PMID- 21734406
TI  - Evaluating the influence of quality control decisions and software algorithms on
      SNP calling for the affymetrix 6.0 SNP array platform.
AB  - OBJECTIVE: Our goal was to evaluate the influence of quality control (QC)
      decisions using two genotype calling algorithms, CRLMM and Birdseed, designed for
      the Affymetrix SNP Array 6.0. METHODS: Various QC options were tried using the
      two algorithms and comparisons were made on subject and call rate and on
      association results using two data sets. RESULTS: For Birdseed, we recommend
      using the contrast QC instead of QC call rate for sample QC. For CRLMM, we
      recommend using the signal-to-noise rate >=4 for sample QC and a posterior
      probability of 90% for genotype accuracy. For both algorithms, we recommend
      calling the genotype separately for each plate, and dropping SNPs with a lower
      call rate (<95%) before evaluating samples with lower call rates. To investigate
      whether the genotype calls from the two algorithms impacted the genome-wide
      association results, we performed association analysis using data from the GENOA
      cohort; we observed that the number of significant SNPs were similar using either
      CRLMM or Birdseed. CONCLUSIONS: Using our suggested workflow both algorithms
      performed similarly; however, fewer samples were removed and CRLMM took half the
      time to run our 854 study samples (4.2 h) compared to Birdseed (8.4 h).

PMID- 21734407
TI  - A dimension reduction approach for modeling multi-locus interaction in case
      control studies.
AB  - Studying one locus or one single nucleotide polymorphism (SNP) at a time may not
      be sufficient to understand complex diseases because they are unlikely to result
      from the effect of only one SNP. Each SNP alone may have little or no effect on
      the risk of the disease, but together they may increase the risk substantially.
      Analyses focusing on individual SNPs ignore the possibility of interaction among
      SNPs. In this paper, we propose a parsimonious model to assess the joint effect
      of a group of SNPs in a case-control study. The model implements a data reduction
      strategy within a likelihood framework and uses a test to assess the statistical
      significance of the effect of the group of SNPs on the binary trait. The primary
      advantage of the proposed approach is that the dimension reduction technique
      produces a test statistic with degrees of freedom significantly lower than a
      multiple logistic regression with only main effects of the SNPs, and our
      parsimonious model can incorporate the possibility of interaction among the SNPs.
      Moreover, the proposed approach estimates the direction of association of each
      SNP with the disease and provides an estimate of the average effect of the group
      of SNPs positively and negatively associated with the disease in the given SNP
      set. We illustrate the proposed model on simulated and real data, and compare its
      performance with a few other existing approaches. Our proposed approach appeared
      to outperform the other approaches for independent SNPs in our simulation
      studies.

PMID- 21734408
TI  - Gene expression and biochemical characterization of Azotobacter vinelandii
      cyclophilins and Protein Interaction Studies of the cytoplasmic isoform with dnaK
      and lpxH.
AB  - The soil nitrogen-fixing bacterium Azotobacter vinelandii possesses two
      cyclophilins, comprising putative cytoplasmic and periplasmic isoforms,
      designated as AvPPIB and AvPPIA, respectively. Both recombinant cyclophilins have
      been purified and their peptidyl-prolyl cis/trans isomerase activity against Suc
      Ala-Xaa-Pro-Phe-pNA synthetic peptides has been characterized. The substrate
      specificity of both cyclophilins is typical for bacterial cyclophilins, with Suc
      Ala-Ala-Pro-Phe-pNA being the most rapidly catalyzed substrate. The cytoplasmic
      cyclophilin also displays a chaperone function in the citrate synthase thermal
      aggregation assay. Using real-time quantitative RT-PCR, we demonstrate that
      AvppiB is expressed under various physiological and growth conditions, mainly
      upregulated by acetate and downregulated by the stationary growth state, while
      AvppiA shows a tendency for downregulation under the tested conditions. Further,
      we identified chaperone protein dnaK and UDP-2, 3-diacylglucosamine hydrolase
      lpxH as probable interacting partners of AvPPIB and we demonstrate their physical
      interaction by coexpression studies. An increase in AvPPIB PPIase activity in the
      presence of AvdnaK and a decrease in the presence of AvlpxH further confirms each
      interaction. However, the PPIase activity does not seem to be essential for those
      interactions since AvPPIB active site mutants still interact with dnaK and lpxH,
      while their minor PPIase activity cannot be modulated by the interaction.

PMID- 21734409
TI  - Dietary Perilla seed oil supplement increases plasma omega-3 polyunsaturated
      fatty acids and ameliorates immunoglobulin A nephropathy in high immunoglobulin A
      strain of ddY mice.
AB  - BACKGROUND/AIMS: The beneficial effects of omega-3 polyunsaturated fatty acids (n
      3 PUFA) in the treatment of immunoglobulin A nephropathy (IgAN) have been
      reported. Perilla frutescens (Linn.) Britton var. frutescens is grown in Eastern
      Asia and its seed (perilla seed) is rich in alpha-linolenic acid, an n-3 PUFA. We
      investigated the antinephritic effects of perilla seed oil in a mouse model of
      IgAN. METHODS: Ten-week-old high IgA ddY mice were fed diets containing either
      perilla seed oil (PS group) or corn oil (C group, control). After 20 weeks, we
      compared body weight, blood pressure, serum creatinine levels, IgA levels, fatty
      acid composition, urinary protein excretion, mesangial matrix expansion, and
      glomerular transforming growth factor-beta1 mRNA expression between groups.
      RESULTS: Serum n-3 PUFA levels were higher in the PS group than the C group
      (p<0.001). Blood urea nitrogen levels were lower (p=0.0246) and urinary protein
      excretion was reduced (p=0.0198) in the PS group. Mesangial matrix expansion
      (p=0.0063) and glomerular transforming growth factor-beta1 mRNA expression
      (p=0.0291) were suppressed in the PS group. No significant differences between
      groups were found in body weight, blood pressure, serum IgA, and creatinine
      levels. CONCLUSIONS: Dietary perilla seed oil supplement could suppress the
      progression of IgAN.

PMID- 21734410
TI  - Hypertonic stress promotes the upregulation and phosphorylation of zonula
      occludens 1.
AB  - Tight junction molecules form a barrier between adjacent cells and mediate the
      cells' ability to develop membranes that constitute boundaries of different
      compartments within the body. Membranes with selective ion and water passage are
      important for the electrolyte and water homeostasis in the kidney. Due to their
      role in the urinary concentration process, renal medullary cells are exposed to
      hyperosmotic stress. Therefore, we were interested in the question of how mouse
      inner medullary collecting duct cells (mIMCD3) manage to maintain their cell-cell
      contacts, despite hypertonicity-induced cell shrinkage. Employing mRNA expression
      analysis, we found that the zonula occludens type 1 (Zo-1), multi-PDZ domain
      protein 1 (MUPP1) and cortactin mRNA levels were upregulated in a tonicity
      dependent manner. Using Western blot analysis, immunoprecipitation and
      immunofluorescence, we show that the Zo-1 protein is upregulated, phosphorylated
      and linked to the actin cytoskeleton in response to hypertonic stress. After cell
      exposure to hypertonicity, rearrangement of the actin cytoskeleton resulted in a
      stronger colocalization of actin fibres with Zo-1. Urea, which generates
      hyperosmolality, but no transcellular gradient, did not induce changes in Zo-1
      protein expression or actin rearrangement. This data indicates that Zo-1 is a
      response protein to inner medullary tonicity and that extracellular stressors can
      promote Zo-1 protein expression, tyrosine phosphorylation and cytoskeleton
      association.

PMID- 21734411
TI  - Brief report: phase II multicenter study of temozolomide in patients with
      cisplatin-resistant germ cell tumors.
AB  - PURPOSE: To determine the activity and toxicity of temozolomide in a phase II
      multicenter trial in patients diagnosed with relapsed or cisplatin-refractory
      germ cell tumors. PATIENTS AND METHODS: During a recruitment period of 30 months,
      20 patients received temozolomide 150 mg/m(2)/day p.o. for 5 days every 4 weeks,
      escalating to 200 mg/m(2)/day if grade II toxicity was not observed in the first
      cycle. Eligibility criteria were tumor progression or relapse after previous
      cisplatin and ifosfamide-containing chemotherapy, creatinine clearance of >40
      ml/min, and a performance status of 0-2. RESULTS: The median age was 38 years
      (range 27-56). Seventeen patients had nonseminomatous tumors, and 3 had
      seminomatous tumors. Six of the patients had extragonadal primary tumors (3
      retroperitoneal and 3 mediastinal). The median number of prior cisplatin
      containing cycles was 11 (range 7-20). Eight patients received prior high-dose
      chemotherapy and 14 were refractory or absolutely refractory to cisplatin. A
      total of 45 cycles were administered. Two partial responses lasting 9 and 3.5
      months (overall response rate 10%, 95% CI 1.2-31.7) were observed. One of these
      responses was seen in a patient with a cisplatin-refractory tumor that had
      previously been treated with high-dose chemotherapy. The median time to
      progression and the median overall survival were 1.5 and 3.1 months,
      respectively. Grade III hematological toxicity consisted of thrombocytopenia in 2
      patients and anemia in 1 patient. No grade IV toxicity was observed. CONCLUSIONS:
      Temozolomide had some activity in heavily pretreated patients resistant to
      cisplatin-based chemotherapy.

PMID- 21734412
TI  - Emerging therapeutic targets in osteoncology.

PMID- 21734413
TI  - The role of CXCR4 in the prediction of bone metastases from breast cancer: a
      pilot study.
AB  - OBJECTIVE: The chemokine receptor CXCR4 is involved in tumor growth and homing of
      cancer cells to distant sites. The aim of our retrospective case-control study
      was to evaluate whether CXCR4 expression is more effective than conventional
      markers (estrogen receptor and HER-2) in predicting bone relapse in breast
      cancer. METHODS: CXCR4 expression was evaluated by immunohistochemical staining
      in paraffin-embedded tissue sections of primary breast cancers from 20 patients
      with bone metastases (BM), 10 with visceral metastases (VM) and 10 with no
      evidence of disease (NED) at a median follow-up of 10.5 years (range 10.1-11.8).
      RESULTS: Cytoplasmic CXCR4 expression was high in BM patients (45%, 95% CI 23
      67), much lower in NED patients (10%, 95% CI 0-29) and negative in the VM group.
      CXCR4 coexpression in the nucleus and cytoplasm was observed in about half of the
      BM patients (45%) but never in NED or VM patients (p = 0.013). Conversely,
      estrogen receptor-positive and HER-2-negative status identified 80 and 95% of
      bone relapse patients, respectively, but did not discriminate between cases and
      controls. CONCLUSIONS: Our results suggest a pivotal role of CXCR4 expression as
      a predictor of BM in primary breast cancer. A larger study is ongoing to confirm
      these results.

PMID- 21734414
TI  - Polymorphisms of estrogen receptors: risk factors for invasive melanoma - a
      prospective study.
AB  - Cross-sectional studies have reported associations between a number of
      polymorphisms in the estrogen receptor alpha (ERalpha) gene and the body mass
      index, hypertension, coronary flow reserve, coronary atherosclerosis, and
      osteoporosis. There are currently no data examining the genetic polymorphisms of
      the ERalpha and estrogen receptor beta (ERbeta) genes in melanoma patients. The
      aims of this study were to investigate the associations of genetic polymorphisms
      of the ERalpha and ERbeta genes with melanoma risk. The study group consisted of
      consecutive patients who visited the Department of Dermatology of the University
      of Florence between March 2005 and July 2007 for surgical excision of melanoma.
      In our study, homozygosity for the wild-type alleles showed different results at
      the PvuII, XbaI, and AluI restriction sites. Only the AluI site showed a lower
      proportion of the A allele in the melanoma group compared to the control group;
      the P and X alleles were lower in the control group than in the melanoma group.
      The distribution of wild-type alleles is important because these alleles have a
      protective role in the expression of altered proteins, which involves the ERs in
      our case. Because of the phenotypic prevalence of the wild-type allele, the
      heterozygotes did not express the polymorphism. The homozygosity of the
      polymorphic-type alleles shows that a alleles are more frequent in the case group
      than in the control group, with proportions of 43.8 and 39.5%, respectively.
      These results suggest that a polymorphism at the AluIrestriction site correlates
      with a higher proportion of melanoma. Thus, the polymorphism of ERbeta could
      ascribe to a higher susceptibility to melanoma.

PMID- 21734415
TI  - Second-line treatment with intravenous gemcitabine and oral etoposide in platinum
      resistant advanced ovarian cancer patients: results of a phase II study.
AB  - OBJECTIVE: The outcome of advanced ovarian cancer patients has not significantly
      improved since the introduction of platinum. One of the major reasons for this
      failure is the lack of an effective second-line treatment. In this phase II trial
      we tested the combination of gemcitabine and etoposide in 2 different groups of
      patients. Group 1 consisted of patients showing disease progression or relapse
      within 6 months of first-line platinum-based chemotherapy. Group 2 comprised
      heavily pretreated patients showing progression during the last chemotherapy
      attempt. METHODS: Thirty-four patients were enrolled. Gemcitabine was
      administered at a dose of 1,000 mg/m(2) on days 1 and 8 and etoposide was
      administered orally at 100 mg/day on days 8-12 for 6 courses. RESULTS: Eighteen
      patients (52.9%) had an objective response and the median duration of the
      response was 10.3 months. Our chemotherapy regimen showed a low toxicity and good
      patient compliance. In 5 patients the treatment had to be delayed and in only 2
      patients it was discontinued. CONCLUSIONS: The combination of gemcitabine and
      oral etoposide seems to be a safe and effective second-line treatment for
      platinum-resistant ovarian cancer patients. Additional data on larger series are
      warranted to better define the activity of this combination regimen.

PMID- 21734416
TI  - Immunochemistry and lung cancer: application in diagnosis, prognosis and targeted
      therapy.
AB  - Immunochemistry is now an established ancillary technique in lung cancer
      diagnosis. Not only does it help in supporting the morphological diagnosis of
      malignancy, but its role now extends to the determination of cell lineage,
      ascertaining the primary site of tumour origin and contributing to decisions on
      prognosis and treatment. Early detection and confirmation of lung cancer
      facilitate early treatment decisions. Lung cancer management now has a
      multidisciplinary approach which includes cytopathologists and clinicians. Some
      clinicians may not understand what immunochemistry is and what its role is in
      lung cancer diagnosis, prognosis and therapy. The purpose of this paper is to
      define immunochemistry, on the background of basic respiratory airway epithelial
      structure and cancer biology, and discuss its application in the diagnosis,
      treatment and determination of prognosis of lung cancer.

PMID- 21734417
TI  - High-dose ifosfamide as second- or third-line chemotherapy in refractory bone and
      soft tissue sarcoma patients.
AB  - INTRODUCTION: For patients with refractory bone and soft tissue sarcoma (STS),
      treatment options have been limited. Ifosfamide is an alkylating agent with well
      demonstrated efficacy against STS, and dose-dependent activity. The aim of this
      retrospective study was to evaluate the response rate, progression-free survival
      (PFS), progression-free rate (PFR), and median duration of response to high-dose
      ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced
      bone sarcoma and STS. PATIENTS AND METHODS: Thirty metastatic, unresectable
      sarcoma patients who were treated with HDI chemotherapy between May 1999 and
      November 2007 were included in the analysis. In total, 106 cycles (median 3
      cycles; range 1-8 cycles) were administered. Twenty-one patients received
      treatment as second-line chemotherapy, and 9 patients as third-line treatment.
      HDI was given at a dose of 2 g/m(2) over 3 h, and at a dose of 2 g/m(2) per day;
      continuous infusion was administered on 6 consecutive days (2 g/m(2)/6 days)
      every 3 weeks. RESULTS: After a median follow-up of 49 months (range 10-114),
      median PFS was 2.9 months (range 0.4-9.3) and median overall survival 8.7 months
      (range 0.4-57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%),
      respectively. Median response duration of HDI was 2.9 months (range 0.7-7.6). Of
      the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial
      response, and 4 (14%) stable disease, and overall disease control was 39%. Two
      responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled
      disease by HDI had a synovial sarcoma. Two patients were not evaluable because
      they were switched to another treatment due to ifosfamide-induced encephalopathy.
      Grade 3-4 neutropenia was seen in 13 (43%) patients, and treatment-related death
      was observed in one patient. CONCLUSION: HDI at a total dose of 14 g/m(2) with
      mesna is still an active salvage regimen, particularly in patients with synovial
      sarcomas.

PMID- 21734418
TI  - Final results of ERASME-4: a randomized trial of first-line docetaxel plus either
      capecitabine or epirubicin for metastatic breast cancer.
AB  - OBJECTIVE: To assess the efficacy of capecitabine plus docetaxel (XT) versus
      epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer
      (MBC). PATIENTS AND METHODS: Patients with no prior chemotherapy for MBC were
      randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m(2) twice
      daily, days 1-14; docetaxel 75 mg/m(2), day 1) or ET (epirubicin 75 mg/m(2), day
      1; docetaxel 75 mg/m(2), day 1). The primary endpoint was non-progression rate 6
      months after randomization. The planned sample size was 106 patients based on a
      randomized, phase II selection design. RESULTS: Between April 2004 and January
      2007, 68 patients were randomized, giving 82% power to select the best regimen
      according to a 6-month non-progression rate. Slow accrual led to premature study
      termination. Baseline characteristics were generally well balanced between arms.
      The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p =
      0.36). After 42 months' median follow-up, median progression-free survival was
      12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were
      consistent with previous experience. CONCLUSION: Further larger studies are
      warranted to validate these results. Despite more grade 3 hand-foot syndrome,
      first-line XT may be a valid alternative to ET, potentially improving efficacy.

PMID- 21734419
TI  - Tumor topoisomerase II alpha status and response to anthracycline-based
      neoadjuvant chemotherapy in breast cancer.
AB  - OBJECTIVES: Individualized chemotherapy for breast cancer improves the outcome.
      Anthracyclines target the enzyme topoisomerase IIalpha (TOP2A). We set out to
      perform a retrospective study of the presence of gene abnormalities and the
      expression of TOP2A in a cohort of breast cancer patients treated with
      neoadjuvant anthracycline-based chemotherapy. METHODS: Forty-three patients with
      45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without
      capecitabine chemotherapy. The TOP2A status of the cancers, determined
      retrospectively by fluorescent in situ hybridization and immunohistochemistry,
      was analyzed in relation to the standard clinical and pathological data. RESULTS:
      Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%)
      and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human
      epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%)
      overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A
      exhibited a strong correlation with the expression of Ki67 (R = 0.743, p <
      0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p =
      0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A
      was not related to the amplification of the TOP2A gene or the HER2 status of the
      tumor. The proportions of Ki67- and TOP2A-positive tumor cells were significantly
      reduced after chemotherapy (56.1 +/- 23.6 vs. 19.0 +/- 27.7%, p = 0.004, and 41.0
      +/- 27.9 vs. 12.7 +/- 24.8%, p < 0.001, respectively). The development of pCR was
      related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A
      expression (p = 0.037). The expression of TOP2A was an independent predictor of
      pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016-2.096, p = 0.041). After a
      median follow-up time of 31.0 months, neither relapse-free survival nor overall
      survival was related to the tumor response. CONCLUSIONS: TOP2A expression is a
      marker of the tumor's proliferation rate and sensitivity to anthracycline-based
      chemotherapy, and does not depend on the amplification of its gene.

PMID- 21734420
TI  - Expression of keratin 19 is related to high recurrence of hepatocellular
      carcinoma after radiofrequency ablation.
AB  - OBJECTIVE: Keratin (K) 19 positivity has been reported to be a useful predictive
      marker for recurrence in patients with hepatocellular carcinoma (HCC) who have
      undergone hepatic resection. We investigated the clinical usefulness of K19
      positivity in patients who had received curative radiofrequency ablation (RFA).
      METHODS: We retrospectively evaluated the clinicopathological features, including
      imaging and K19 expression, in 246 patients with HCC who were within the Milan
      criteria and had received curative RFA. Using a two-step insertion method, tumor
      biopsies were obtained just prior to RFA and were evaluated histologically.
      RESULTS: Tumor seeding due to liver biopsy and RFA was not observed. Ten patients
      (4.1%) had K19-positive HCC. Imaging findings were similar between K19-positive
      and -negative HCC (p = 0.187). Nine out of 10 patients (90%) who had K19-positive
      HCC had recurrence of HCC after RFA, and intrahepatic recurrences were observed
      within 12 months in 6 out of 10 (60.0%). K19 positivity was a significant risk
      factor for recurrence (p < 0.0001) and early recurrence (<1 year after RFA; p
      =0.012). K19 expression (p = 0.016) was an independent risk factor for tumor
      status exceeding the Milan criteria after RFA. CONCLUSION: Expression of K19 is
      related to high recurrence of HCC after curative RFA.

PMID- 21734421
TI  - Her-2/neu overexpression due to polysomy 17 in breast cancer: molecular testing
      to guide therapeutic options.
AB  - BACKGROUND: Fluorescent in situ hybridization (FISH) equivocal results for Her
      2/neu still pose a diagnostic dilemma in oncology practice. In this study, we
      evaluate if Her-2/neu mRNA expression is an alternative to FISH for detecting Her
      2/neu positivity. PATIENTS AND METHODS: Archival paraffin blocks of 54 breast
      cancer patients were analyzed for Her-2/neu status using immunohistochemistry
      (IHC), FISH, and Her-2/neu gene expression using mRNA. RESULTS: There was a 100%
      positive agreement and 64.7% negative agreement of Her-2/neu mRNA expression with
      respect to the reference standard (FISH), with the kappa value for agreement
      being 0.36. mRNA levels correlated positively and strongly with FISH ratio and
      IHC positivity. For Her-2/neu mRNA expression, Her-2/neu copy number was a
      significant predictor indicating that mRNA expression is independent of polysomy
      status. CONCLUSIONS: Her-2/neu mRNA expression may help tide over ambiguity posed
      by polysomy and FISH equivocal samples.

PMID- 21734422
TI  - Quality assured health care in certified breast centers and improvement of the
      prognosis of breast cancer patients.
AB  - BACKGROUND: Increasing effort has been put in the implementation and
      certification of breast centers in order to establish standardized, quality
      assured health care for breast cancer patients. The aim of this analysis was to
      investigate whether patients treated in certified breast centers (CBC) have a
      favorable prognosis as compared to patients treated outside of certified breast
      treatment units. PATIENTS AND METHODS: The data of 3,940 patients with invasive
      nonmetastatic breast cancer were analyzed with regard to differences in patient
      and tumor characteristics and crude overall survival according to diagnosis in or
      outside CBC in Middle Franconia, Germany. Patient, tumor, and follow-up data were
      obtained from the clinical cancer registry. RESULTS: Patients in CBC were
      younger, and had lower disease stages and lower grading. Independent of the
      effects of these variables on overall survival, being treated at a CBC added to
      the prediction of overall survival. Patients treated at a CBC had a hazard ratio
      of 0.70 (95% confidence interval 0.52-0.93) in the adjusted Cox model.
      CONCLUSIONS: Independent from common prognostic factors, diagnosis and treatment
      of breast cancer at a CBC improves the prognosis of patients. It can be
      hypothesized that this effect is mediated through quality assured health care
      provided by the certification process.

PMID- 21734423
TI  - A randomized phase II study of drug-eluting beads versus transarterial
      chemoembolization for unresectable hepatocellular carcinoma.
AB  - BACKGROUND: Transcatheter arterial chemoembolization (TACE) is the standard
      treatment in selected patients with unresectable hepatocellular carcinoma (HCC).
      Drug-eluting particles are developed to reduce side effects and improve efficacy.
      We present safety data of a prospective randomized phase II study with
      doxorubicin-eluting superabsorbent polymer (SAP) microspheres. MATERIAL AND
      METHODS: We prospectively included 30 HCC patients with different Barcelona
      Clinic Liver Cancer (BCLC) stages (A = 3, B = 19, C = 8) and randomly assigned
      them to receive conventional TACE (n = 14) (control group) or doxorubicin-eluting
      SAP microspheres (n = 16). The doxorubicin plasma level was assessed at different
      time points, biochemical analysis was performed, and side effects were reported
      following the Common Toxicity Criteria. Tumor response was assessed at 6 weeks
      according to the modified Response Evaluation Criteria in Solid Tumors (RECIST)
      criteria. RESULTS: There was a significantly lower plasma peak concentration
      (Cmax) of doxorubicin and smaller area under the curve (AUC) with SAP
      microspheres (mean Cmax 495 +/- 293.9 ng/ml, mean AUC 69.7 +/- 26.9 ng/ml min)
      compared to controls (mean Cmax 1,928 +/- 560.8 ng/ml, mean AUC 165 +/- 32.3
      ng/ml/min; both p < 0.001). Furthermore, there were less grade 3 and no grade 4
      adverse events in the SAP microsphere group. Tumor response was comparable
      between the groups. CONCLUSIONS: TACE with SAP microspheres leads to low plasma
      levels of the cytotoxic drug and therefore minimizes toxicity compared to
      conventional TACE.

PMID- 21734424
TI  - Phase II study of weekly irinotecan plus cisplatin in patients with previously
      untreated extensive-stage extrapulmonary small cell carcinoma.
AB  - BACKGROUND: The regimen of weekly irinotecan plus cisplatin (IP) is used for
      treatment of small cell lung cancer (SCLC). We conducted a phase II trial to
      evaluate the efficacy and toxicity of weekly IP in patients with previously
      untreated extensive-stage extrapulmonary small cell carcinoma (EPSCC). PATIENTS
      AND METHODS: 15 patients with previously untreated extensive-stage EPSCC were
      enrolled. They received 60 mg/m2 of irinotecan on days 1, 8 and 15, and 25
      mg/m(2) of cisplatin days 1-3. This regimen was given every 28 days, and efficacy
      was evaluated after 2 cycles. RESULTS: Objective responses were observed in 10
      patients (66.7%), including 3 complete responses (20%) and 7 partial responses
      (46.7%). The median time to tumor progression was 4.5 months, the median survival
      time was 11.4 months, and the 1-year survival rate was 46.7%. Toxicities were
      relatively mild, and there were no treatment-related deaths. CONCLUSIONS: Weekly
      IP has significant activity in extensive-stage EPSCC. The regimen was well
      tolerated, with acceptable myelosuppression and treatment-related diarrhea.

PMID- 21734425
TI  - Mantle cell lymphoma and anti-MuSK-positive Myasthenia gravis.

PMID- 21734426
TI  - Bilateral breast enlargement and reddish skin macules as first signs of acute
      lymphoblastic T cell leukemia.

PMID- 21734427
TI  - Acute promyelocytic leukemia with trisomy 8 and del(9)(q22) after treatment of
      cervical cancer with concurrent chemoradiotherapy: a case report.

PMID- 21734428
TI  - Small-bowel obstruction caused by duodenal compression of a paraaortic
      lymphocele.

PMID- 21734429
TI  - Recovery from carcinomatous meningitis by erlotinib.

PMID- 21734430
TI  - Pancreatogenic diabetes after pancreatic resection.
AB  - The loss of pancreatic parenchyma resulting from pancreatic resection causes an
      extreme disruption of glucose homeostasis known as pancreatogenic diabetes. This
      form of glucose intolerance is different from the other forms of diabetes
      mellitus in that affected individuals suffer frequent episodes of iatrogenic
      hypoglycemia. The development of sophisticated surgical procedures, improved
      postoperative care, and the capacity for early diagnosis of disease has prolonged
      life expectancy after pancreatic resection. For this reason, pancreatogenic
      diabetes is now attracting attention as the primary factor influencing quality of
      life in patients who have undergone this procedure. The incidence of new-onset
      diabetes mellitus after pancreatic resection increases as the follow-up period
      after surgery becomes longer and is related to the progression of underlying
      disease, the type of surgery, and the extent of resection. The pathophysiology of
      pancreatogenic diabetes is related to pancreatic hormone deficiency and the
      altered responses of the liver and peripheral organs to lower than normal hormone
      levels. Hyperglycemia occurs when the amount of insulin produced or administered
      is insufficient because of unsuppressed hepatic glucose production secondary to a
      deficiency in pancreatic polypeptide. In contrast, patients lapse into
      hypoglycemia when insulin is barely excessive because of enhanced peripheral
      insulin sensitivity and glucagon deficiency. Nutritional state, pancreatic
      exocrine function and intestinal function also affect glycemic control. Insulin
      replacement is considered to be the main treatment option for insulin dependent
      pancreatogenic diabetes. Pancreatic polypeptide replacement and islet
      autotransplantation have potential as new approaches to treating patients with
      pancreatogenic diabetes after pancreatic resection. and IAP.

PMID- 21734431
TI  - Osthol, a coumarin isolated from common cnidium fruit, enhances the
      differentiation and maturation of osteoblasts in vitro.
AB  - The effect of osthol on osteoblasts was investigated in primary osteoblastic
      cells isolated from newborn Wistar rats. Osthol was supplemented into cultured
      medium at 10-7, 10-6, 10-5 and 10-4 mol/l, respectively. No stimulating effect
      was found on cell proliferation, but 10-5 mol/l osthol caused a significant
      increase in alkaline phosphatase (ALP) activity. Osteogenic differentiation
      markers were examined over a period of time at this concentration, and compared
      with control cells that were not supplemented with osthol. The results showed
      that the ALP activity, osteocalcin secretion and calcium deposition level in
      cells treated with osthol were 1.52, 2.74 and 2.0 times higher, respectively,
      than in the control cells. Results of ALP histochemical staining and mineralized
      bone nodule assays both showed that the number and area achieved in osthol
      treated cells were 1.53-fold higher than in control cells. The gene expression of
      the growth and transcription factors basic fibroblast growth factor, insulin-like
      growth factor I, bone morphogenetic protein 2 (BMP-2), runt-related gene 2 (Runx
      2) and osterix, which are associated with bone development, were also
      investigated. The increase in mRNA expression was 1.94, 1.74, 1.68, 1.83 and 2.31
      times, respectively, higher compared to the control. Furthermore, osthol
      increased the protein expression of p38 mitogen-activated protein kinase (MAPK)
      and type I collagen. p38MAPK protein and collagen in osthol-treated cells were
      1.42 and 1.58 times higher in osthol-treated cells compared to the control. The
      results of these studies support the conclusion that osthol significantly
      enhances the osteogenic differentiation of cultured osteoblasts. The results also
      indicated that osthol could stimulate the osteoblastic differentiation of rat
      calvarial osteoblast cultures by the BMP-2/p38MAPK/Runx-2/osterix pathway and
      that osthol may be used as an important compound in the development of new
      antiosteoporosis drugs.

PMID- 21734432
TI  - Health literacy and public health genomics: innovation management by citizens.

PMID- 21734433
TI  - Health literacy: the essential catalyst for the responsible and effective
      translation of genome-based information for the benefit of population health.
AB  - The complexity and novelty of public health genomics poses a challenge to ensure
      effective and responsible translation of genome-based information for the benefit
      of population health. The aim of this article is to provide literature-based
      insight into how the concept of health literacy can act as a catalyst for the
      translation process and to comment on the necessity to adapt new perspectives in
      a rapidly changing world, such as e.g. the health literacy-friendly approach of
      Google. Taking advantage of the potential of health literacy in the population
      along with a recognized role of health professionals as knowledge brokers and
      'nudges' will benefit the efficiency and responsibility of translating genome
      based knowledge.

PMID- 21734434
TI  - Genome-based health literacy: a new challenge for public health genomics.
AB  - So far health literacy has not been sufficiently discussed in the context of
      public health genomics. Primarily, not genomic but rather genome-based health
      information needs to be addressed taking into account genome-environment
      interactions and integrating all health determinants including genomics into a
      systemic and holistic approach. Translating findings from epigenomics and systems
      biomedicine will help to understand that individual biological pathways or
      networks are permanently interacting with environmental networks such as social
      networks. Thus, in the end also health literacy will become personalized. Genome
      based health literacy is challenged by the question of which information is
      relevant for the individual, for what purpose, and at what time during the
      lifespan. Public health tools and expertise already in place can and should be
      used to tackle these huge challenges.

PMID- 21734435
TI  - Ego disturbances in the sense of Kurt Schneider: historical and phenomenological
      aspects.
AB  - The phenomena which were grouped together by Kurt Schneider to constitute the ego
      disturbances have always been of particular diagnostic relevance for
      schizophrenia. The manner in which these symptoms are described and distinguished
      from other psychopathological symptoms has generally been rather imprecise. The
      introduction of phenomenological methods into the field of psychiatry led to
      considerable improvements in symptom descriptions and to a clearer distinction
      between psychotic and nonpsychotic experience. Continued developments in
      phenomenology have further incorporated aspects of schizophrenic symptom
      development and in doing so have brought so-called transitional phenomena and the
      core schizophrenic syndrome into focus. The ego disturbances accordingly appear
      to stem from a particular form of depersonalization which is described as a
      modified sense of mineness and which can be distinguished from the neurotic
      experience of depersonalization.

PMID- 21734436
TI  - Maternal rejection of the young child: present status of the clinical syndrome.
AB  - This article reviews severe disorders of the mother-infant relationship involving
      emotional rejection of the infant in the first year of its life. Infants exposed
      to their mother's hatred and rage may suffer far-ranging and long-term
      disadvantages, and are at risk of maltreatment. Diagnosis, therapy and research
      have been hampered by the lack of recognition of this clinical syndrome in the
      classifications. The imminent revision of these classificatory systems must
      include them.

PMID- 21734437
TI  - Treatment of Alice in Wonderland syndrome and verbal auditory hallucinations
      using repetitive transcranial magnetic stimulation: a case report with fMRI
      findings.
AB  - BACKGROUND: Alice in Wonderland syndrome (AIWS) is a rare cluster of CNS symptoms
      characterized by visual distortions (i.e. metamorphopsias), body image
      distortions, time distortions, and deja experiences. Verbal auditory
      hallucinations (VAHs) are the most prevalent type of hallucination in adults with
      or without a history of psychiatric illness. Here, we report the case of a woman
      with AIWS, long-lasting VAHs, and various additional perceptual and mood
      symptoms. METHODS: Semi-structured interviews were used to assess symptoms, and
      functional MRI (fMRI) was employed to localize cerebral activity during self
      reported VAHs. Treatment consisted of repetitive transcranial magnetic
      stimulation (rTMS) at a frequency of 1 Hz at T3P3, overlying Brodmann's area 40.
      RESULTS: Activation during VAHs was observed bilaterally in the basal ganglia,
      the primary auditory cortex, the association auditory cortex, the temporal poles,
      and the anterior cingulated gyrus. The left and right inferior frontal gyri
      (Broca's area and its contralateral homologue) were involved, along with the
      dorsolateral prefrontal cortex. Interestingly, synchronized activation was
      observed in the primary visual cortex (areas V1 and V2), and the bilateral dorsal
      visual cortex. The higher visual association cortex also showed significant, but
      less prominent, activation. During the second week of rTMS treatment, not only
      the VAHs, but also the other sensory deceptions/distortions and mood symptoms
      showed complete remission. The patient remained free of any symptoms during a 4
      month follow-up phase. After 8 months, when many of the original symptoms had
      returned, a second treatment phase with rTMS was again followed by complete
      remission. CONCLUSIONS: This case indicates that VAHs and metamorphopsias in AIWS
      are associated with synchronized activation in both auditory and visual cortices.
      It also indicates that local rTMS treatment may have global therapeutic effects,
      suggesting an effect on multiple brain regions in a distributed network. Although
      a placebo effect cannot be ruled out, this case warrants further investigation of
      the effects of rTMS treatment in AIWS.

PMID- 21734438
TI  - Comparative analysis of skin surface lipids of the labia majora, inner thigh, and
      forearm.
AB  - The purpose of this study was to develop a procedure for the collection of skin
      surface corneocyte lipids from the semioccluded and intimate regions of the labia
      majora and inner thigh of women, to evaluate the polar and nonpolar composition,
      and to compare the distribution of the lipid classes relative to a collection of
      lipids from the forearm. The solvent system of ethanol-cyclohexane was well
      tolerated across all sites. While the yield of polar lipids was similar across
      all 3 sites, there were only marginal differences in the relative abundance of
      ceramides, a class of lipids closely associated with skin barrier activity. The
      yield of neutral lipids was significantly less for the labia majora and was
      associated with a reduced yield of wax esters, triglycerides and free fatty
      acids, likely associated with reduced sebaceous gland activity. Factors that may
      contribute to an inferior skin barrier activity for the labia majora are
      discussed and suggest a possible deficiency of omega-6 fatty acid linked to the
      sphingosine base of ceramide EOS.

PMID- 21734439
TI  - Rationality of administered gentamicin dose in cerebral coma patients treated in
      an intensive care unit.
AB  - Gentamicin is still widely used in the treatment of patients in an intensive care
      unit (ICU). The efficacy of aminoglycosides correlates with the peak serum
      concentration (Cmax), and the toxicity with the minimum serum concentration
      (Cmin). The aim of this study was to determine Cmax and Cmin in serum of cerebral
      coma ICU patients when a dosage of gentamicin of 5 mg/kg body weight was
      administered once daily; to evaluate the rationality of mentioned dose; and to
      identify factors associated with these concentrations. Material and METHODS. A
      total of 24 ICU patients suffering from cerebral coma were included into this
      analysis. A dosage of gentamicin of 5 mg/kg body weight was administered once a
      day. Gentamicin concentrations were tested twice after the first dose infusion
      (immediately and 5 hours after 1-hour infusion). Cmax, Cmin, volume of
      distribution (Vd), and elimination half-life (T1/2) were obtained. RESULTS. The
      mean Cmax was 17.96 (SD, 4.31) ug/mL (range, 10.30-27.87 ug/mL). The desirable
      Cmax (>= 20 ug/mL) was reached only in 6 patients (25%). Cmin was calculated
      using a special pharmacokinetic program "Kinetica." Cmin of 0.5 ug/mL was not
      exceeded in any patient. A correlative analysis indicated a significant inverse
      direct correlation between Cmax and Vd and between Cmax and treatment duration in
      the ICU. An inverse correlation was observed between Cmin and T1/2, evaluation of
      coma according to the Glasgow coma scale, and creatinine clearance. CONCLUSIONS.
      A dosage of 5 mg/kg body weight once a day was not sufficient in cerebral coma
      ICU patients. This dose was not associated with the nephrotoxic effect of
      gentamicin (additional risk factors were absent). It is recommended to obtain
      gentamicin concentration at two time points following administration of the first
      dose (e.g., immediately after 1-hour infusion and 5 hours later), and using a
      special pharmacokinetic software, to calculate a necessary dose and interval of
      administration.

PMID- 21734440
TI  - The comparison of different surgical techniques used for repair of complete
      unilateral cleft lip.
AB  - Up to now, many various techniques have been proposed for the repair of complete
      unilateral cleft lip. The aim of this study was to compare late results of three
      different surgical techniques (C. Tennison, R. Millard, and J. Olekas) used for
      the repair of complete unilateral cleft lip and to analyze their advantages and
      disadvantages. Material and METHODS. Sixty-six patients with nonsyndromic
      complete unilateral cleft lip, alveolus, and palate were examined. For 19
      patients (28.8%), cleft lip repair was performed using the Tennison technique;
      for 20 patients (30.3%), Millard technique; and for 27 patients (40.9%), Olekas
      technique. Results were assessed by score, which was given by analyzing
      standardized photographs of nasolabial triangles. For the assessment, the
      modified scale according to Mortier and Anastassov was used. Separate anatomical
      elements - red lip, white lip, scars, and nose - were assessed. RESULTS. The best
      appearance of the red lip and white lip was found after the Tennison technique.
      Scars and nose looked the best after Olekas cheiloplasty. There were no
      significant differences in the evaluation of red lip and nose appearance
      comparing all three analyzed surgical techniques (P>0.05). Tennison technique
      showed significantly better results in the appearance of the white lip (P<0.05);
      the appearance of scars was significantly better after the Olekas repair
      (P<0.001). CONCLUSIONS. Height of white lip and symmetry of the Cupid's bow were
      better restored by using the Tennison technique. The physiological configuration
      of the white lip and less visible scars were achieved by using the Olekas
      technique. All techniques were equal in red lip and nose formations.

PMID- 21734441
TI  - Activity of neutrophil beta-glucuronidase in diabetic and nondiabetic patients
      with chronic generalized periodontitis and healthy subjects.
AB  - OBJECTIVE. The aim of the study was to establish the dynamics of beta
      glucuronidase activity in subjects suffering from type 1 diabetes and chronic
      untreated generalized periodontitis, subjects suffering from chronic untreated
      generalized periodontitis only, and control subjects not suffering from generic
      diseases with healthy periodontal tissue. MATERIAL AND METHODS. The study
      involved 165 19-50-year-old subjects who were divided into three groups: healthy
      subjects (n=55), subjects with chronic untreated generalized periodontitis
      (n=55), and subjects with type 1 diabetes and chronic untreated generalized
      periodontitis (n=55). Neutrophilic leukocytes of peripheral venous blood were
      exposed to bacterial stimuli: opsonized zymosan, nonopsonized Staphylococcus
      aureus, and prodigiosan. The activity of beta-glucuronidase was determined by the
      spectrofluorimetry method. RESULTS. The diagnostic value of changes in beta
      glucuronidase activity of neutrophilic leukocytes markedly increased in all study
      groups after stimulation of neutrophilic leukocytes by opsonized zymosan,
      nonopsonized Staphylococcus aureus, and prodigiosan as compared to control media
      not exposed to any stimulus (P<0.001). The strongest relationship (canonical
      correlation coefficient eta, 0.993) between the intensity of periodontal
      pathology markers and the activity of beta-glucuronidase of neutrophilic
      leukocytes in incubated media in patients with type 1 diabetes mellitus and
      periodontitis was found under the effect of nonopsonized Staphylococcus aureus.
      CONCLUSIONS. If periodontal impairment is severe, diabetes mellitus possibly
      causes a faster destruction of the periodontal tissue and presents a higher risk
      of periodontitis for patients with diabetes.

PMID- 21734442
TI  - Arthroscopic coracoid transposition for recurrent shoulder anterior instability:
      an operative technique.
AB  - We report a technique of an arthroscopic concomitant Bankart repair with a
      transfer of the coracoid bone block and conjoint tendons for revision anterior
      shoulder instability. The operative procedure consists of an arthroscopic
      transfer of the conjoined tendon with a coracoid and arthroscopic Bankart repair.
      First, a typical Bankart suture anchor procedure with two suture anchors was
      performed into the antero-inferior part of the glenoid rim. After, tenodesis of
      the coraco-biceps tendon was performed in the middle of the subscapularis tendon
      fixing the coracoid bony fragment into a glenoid socket with a bioabsorbable
      interference screw. This operative technique is an alternative in the treatment
      of revision anterior shoulder instability in patients with deficient anterior
      capsule.

PMID- 21734443
TI  - Influence of short breathing stop on the cardiovascular system during exercise
      testing.
AB  - Breathing is both a voluntary and an involuntary action, and the changes in
      breathing intensity or breathing stops has an influence on vegetative functions
      of the body during exercise. The aim of this study was to determine the possible
      changes in cardiovascular parameters when patients shortly stopped to breath at
      the beginning of exercise testing. MATERIAL AND METHODS. Two series of
      investigation were performed. During the first investigation, the psychomotor
      tonus was assessed, and the breathing frequency during exercising was monitored
      in the cohort of 27 healthy adult males who were recruited for the first time to
      be participants of exercise testing. All the participants performed the Roufier
      exercise test (30 squats per 45 s). A 12-lead electrocardiogram was continuously
      recorded during exercise and first two minutes of recovery, and arterial blood
      pressure was measured at each minute of experiment. During the second
      investigation, the influence of short breathing stop for 15 s on the changes in
      cardiovascular functional parameters during exercise test was evaluated. RESULTS.
      The results obtained during the study showed that patients who had increased
      psychomotor tonus stopped the breathing involuntary more frequently at the
      beginning of exercise testing. An involuntary or voluntary breathing stop at the
      beginning of exercising had an influence on the dynamics of cardiovascular
      parameters during exercise and recovery: heart rate increased more slowly; lesser
      changes in the JT interval of electrocardiogram, a trend toward an increase in
      the arterial blood pressure, and a significantly slower recovery of
      cardiovascular parameters were documented. CONCLUSION. An involuntary breathing
      stop caused the changes in cardiovascular parameters during exercise and
      recovery; therefore, functional status might be assessed not so accurately.

PMID- 21734444
TI  - Prevention of amyloid-beta oligomer-induced neuronal death by EGTA, estradiol,
      and endocytosis inhibitor.
AB  - BACKGROUND AND OBJECTIVE. Alzheimer's disease is a progressive neurodegenerative
      disease that is biochemically characterized by the accumulation of amyloid beta
      (Abeta) peptides in the brain. The current hypothesis suggests that Abeta
      oligomers rather than fibrillar aggregates are the most toxic species of Abeta
      though the mechanisms of their neurotoxicity are unclear. The authors have
      previously shown that small Abeta(1-42) oligomers at around 1 uM concentration
      caused rapid (in 24 h) neuronal death in cerebellar granule cell (CGC) cultures.
      In this study, we aimed to investigate whether protracted (up to 7 days)
      incubation of CGC cultures with lower submicromolar concentration of various
      aggregates of Abeta(1-42) had an effect on viability of neurons. In order to get
      some insight into the mechanism of Abeta-induced cell death, we also sought to
      determine whether extracellular Ca(2+) and process of endocytosis contributed to
      Abeta oligomer-induced neurotoxicity and whether pharmacological interventions
      into these processes would prevent Abeta oligomer-induced cell death. MATERIAL
      AND METHODS. Primary cultures of CGC were treated with various aggregate forms of
      Abeta(1-42). Cell viability was assessed by fluorescent microscopy using
      propidium iodide and Hoechst 33342 staining. RESULTS. Exposure of neurons to 500
      nM Abeta(1-42) oligomers for 72-168 h caused extensive neuronal necrosis. Lower
      concentrations (100-250 nM) were not toxic to cells during 7 days of incubation.
      Abeta(1-42) monomers and fibrils had no effect on neuronal viability even after 7
      days of incubation. Treatment of neurons with EGTA, steroid hormone 17beta
      estradiol, and methyl-beta-cyclodextrin significantly reduced Abeta(1-42)
      oligomers-induced neuronal death. CONCLUSIONS. The results show that
      submicromolar concentrations of Abeta(1-42) oligomers were highly toxic to
      neurons during protracted incubation inducing neuronal necrosis that can be
      prevented by chelating extracellular Ca(2+) with EGTA, inhibiting endocytosis
      with methyl-beta-cyclodextrin, or by estradiol, which may protect against
      mitochondrial permeability transition pore opening.

PMID- 21734445
TI  - Attitudes of Lithuanian secondary school children toward addictive behaviors,
      their promoting and preventive factors with regard to the age.
AB  - The aim of this study was to evaluate the attitudes of Lithuanian secondary
      school children toward addictive behaviors, their promoting and preventive
      factors with regard to the age. MATERIAL AND METHODS. The study sample consisted
      of all 5th-, 9th-, and 12th-grade schoolchildren of 6 secondary schools in Kaunas
      and Sakiai (N=856). Schoolchildren were surveyed with a questionnaire consisting
      of the questions about their attitudes and experience regarding addictive
      behaviors and factors promoting and preventing such behaviors. RESULTS. Smoking
      (82.8%), use of illegal drugs (81.0%), and consumption of strong alcoholic
      beverages (80.6%) were most often indicated as addictive behaviors. Consumption
      of light alcoholic beverages and computer gaming were least often indicated as
      addictive behaviors: by 67.2% and 57.1% of respondents, respectively. Less than
      one-third (32.7%) of respondents answered that they had one or more of
      potentially addictive behaviors: computer gaming (27.8%), consumption of light
      alcoholic beverages (24.6%), smoking (16.3%), and consumption of strong alcoholic
      beverages (12.1%). The most significant difference was observed between the
      answers of schoolchildren of 5th and 9th grades. Friends (38.4%), TV (37.9%), and
      Internet (24.6%) were most often mentioned as influencing a wish to try and
      abstain from addictive behaviors. Fear for one's health (74.4%) and possible
      impediment for the life (71.4%) were the most frequently mentioned reasons for
      abstaining from addictive behaviors. CONCLUSIONS. Involvement in potentially
      addictive behaviors and acknowledgement of their risks were found to increase
      with the age of schoolchildren, most significantly from 5th to 9th grades.
      Consumption of light alcoholic beverages was the second most prevalent behavior
      among respondents, highly noticed in advertising, but least often acknowledged as
      addictive behavior. TV and Internet were most often mentioned by respondents as
      mass media influencing their wish to try or abstain from trying addictive
      behaviors. Reasons for abstaining from addictive behaviors differed with regard
      to the age but fears for health and life impediment were most prevalent in all
      grades.

PMID- 21734446
TI  - Quality of obstetric services: perspectives of patients, obstetricians, and
      midwives.
AB  - OBJECTIVE. The aim of this study was to compare the perspectives of patients and
      health care staff on the quality of obstetric services in an obstetric
      department. Material and METHODS. This study was carried out at the Department of
      Obstetrics, Hospital of Lithuanian University of Health Sciences, where 68
      obstetricians and midwives and 334 female patients completed anonymous
      questionnaires. Two different versions of the questionnaire for patients and
      health care staff were prepared with the aim to compare the results of both
      groups. RESULTS. Patients evaluated technical quality of services significantly
      better than health care staff. Other items were showed to have no significant
      differences with the exception of sterility of equipment and premises and
      appearance of physicians. Patients and health care staff had similar opinions
      about professional relationship between patients and physicians: patients can
      expect representation of their interests and evaluation of treatment progress.
      Evaluation of external efficiency revealed that respondents were satisfied with
      health care and would recommend the current health care institution to their
      friends and relatives or would use it again when needed. CONCLUSIONS. Patients
      evaluated technical quality of services significantly better than health care
      staff. The different perceptions of patients and health care staff about
      functional quality and external effectiveness of services in most aspects were
      insignificant.

PMID- 21734447
TI  - [Microsatellite instability and loss of heterozygosity in cancer].
AB  - Literature review on genetic alterations (microsatellite instability and loss of
      heterozygosity) in different types of cancer is presented. Microsatellite
      instability and loss of heterozigosity are significant processes in
      carcinogenesis. The evaluation of microsatellite instability in cancer patients
      might be of clinical importance as a prognostic and predictive factor. The most
      of up-to-date data available are on microsatellite instability in colorectal
      cancer. For other types of cancer, the number of publications on microsatellite
      instability is rapidly increasing.

PMID- 21734448
TI  - Down-regulation of survivin suppresses uro-plasminogen activator through
      transcription factor JunB.
AB  - Survivin, a member of the inhibitors of apoptosis protein family, is expressed
      during development and in various human cancers. However, the clinical relevance
      of survivin in cancer is still a matter of debate. Genes induced by hepatocyte
      growth factor (HGF) were screened using cDNA microarray technology in the stomach
      cancer cell lines, NUGC3 and MKN28. The levels of JunB, survivin, and uro
      plasminogen activator (uPA) were up-regulated in cells treated with HGF in a dose
      dependent manner. HGF-induced up regulation of JunB, survivin, and uPA was
      inhibited by pre-treatment with a MEK inhibitor (PD 98059). HGF-induced up
      regulation of uPA was repressed by survivin knockdown. HGF enhanced the binding
      activity of JunB to the survivin promoter in control cells, but not in the JunB
      shRNA cells. Transfection with survivin- shRNA resulted in a decrement of cell
      proliferation, as determined with MTT assays. In an in vitro invasion assay,
      significantly fewer cells transfected with survivin shRNA than control cells were
      able to invade across a Matrigel membrane barrier. In conclusion, survivin
      appeared to play an important role in the up-regulation of uPA induced by HGF via
      JunB and might contribute to HGF-mediated tumor invasion and metastasis, which
      may serve as a promising target for gastric cancer therapy.

PMID- 21734449
TI  - Continuous hypoxia attenuates paraquat-induced cytotoxicity in the human A549
      lung carcinoma cell line.
AB  - Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and
      widely used herbicide, was commercially introduced in 1962. It is reduced by the
      electron donor NADPH, and then reduced PQ transfers the electrons to molecular
      oxygen, resulting in the production of reactive oxygen species (ROS), which are
      related to cellular toxicity. However, the influence of continuous hypoxia on PQ
      induced ROS production has not fully been investigated. We evaluated in vitro the
      protective effect of continuous hypoxia on PQ-induced cytotoxicity in the human
      carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live
      and dead assay, and by measuring lactate dehydrogenase (LDH) release. To
      elucidate the mechanism underlying this effect, we monitored the
      immunofluorescence of intracellular ROS and measured malondialdehyde (MDA),
      superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities.
      Continuous hypoxia protected the A549 cells from PQ-induced cytotoxicity.
      Continuous hypoxia for a period of 24 h significantly reduced intracellular ROS,
      decreased MDA concentration in the supernatant, and normalized SOD and GPx
      activities. Continuous hypoxia attenuated PQ-induced cell toxicity in A549 cells.
      This protective effect might be attributable to the suppression of PQ-induced ROS
      generation.

PMID- 21734450
TI  - It's all about flaps: Dna2 and checkpoint activation.

PMID- 21734451
TI  - Wip1 contributes to cell homeostasis maintained by the steady-state level of
      Wtp53.
AB  - Wip1, a human protein Ser/Thr phosphatase also called PPM1D, stands for wild type
      p53 induced phosphatase 1. Emerging evidences indicate that Wip1 can act as an
      oncogene largely by turning off DNA damage checkpoint responses. Here we report
      an unrecognized role of Wipl in normally growing cells. Wip1 can be induced by
      wild type p53 under not only stressed but also non-stressed conditions. It can
      trigger G 2/M arrest in wild type p53 containing cells, which was attributed to
      the decreased Cdc2 kinase activity resulting at least partly from a high level of
      inhibitory tyrosine phosphorylation on Cdc2 protein at Tyr-15. Furthermore, we
      also found that Wip1 not only causes G 2/M arrest but also decreases cell death
      triggered by microtubule assembly inhibitor in mouse fibroblasts when wild type
      p53 function was restored. These results indicate that Wip1 can provide ample
      time for wild type p53-containing cells to prepare entry into mitosis and avoid
      encountering mitotic catastrophe. Therefore, Wipl may play important roles in
      cell/tissue homeostasis maintained by wild type p53 under normal conditions,
      enhancing our understanding of how p53 makes cell-fate decisions.

PMID- 21734452
TI  - Zinc, a promising mineral for misfolded p53 reactivation.

PMID- 21734454
TI  - Cdc14B: when a good kid turns bad.

PMID- 21734453
TI  - JunD-mediated repression of GADD45alpha and gamma regulates escape from cell
      death in prostate cancer.
AB  - The AP-1 transcription factor complex has been implicated in a variety of
      biological processes including cell differentiation, proliferation, apoptosis and
      oncogenic transformation. We previously established that activation of the AP-1
      family member JunD contributes to deregulated expression of the anti-apoptotic IL
      6 gene in prostate cancer cells. We now show that inhibition of JunD in prostate
      cancer cells results in GADD45alpha- and gamma-dependent induction of cell death
      and inhibition of tumor growth that is mediated at least partially via c-Jun N
      terminal kinase (JNK) and p38 kinase activation. Apoptosis induction by dominant
      negative JunD and JNK and p38 kinase activation are impeded upon knock down of
      GADD45alpha and gamma expression by small interfering RNA, most vividly
      demonstrating the central role of GADD45alpha and gamma in JunD-mediated escape
      of prostate cancer cells from programmed cell death.

PMID- 21734455
TI  - SAYP: a bridge connecting specific and general transcription regulators.

PMID- 21734456
TI  - Breast tumor microenvironment: in the eye of the cytokine storm.

PMID- 21734458
TI  - Fuel for cancer cells?

PMID- 21734457
TI  - BRCT domains: easy as one, two, three.
AB  - BRCA1 C-terminal (BRCT) domains are integral signaling modules in the DNA damage
      response (DDR). Aside from their established roles as phospho-peptide binding
      modules, BRCT domains have been implicated in phosphorylation-independent protein
      interactions, DNA binding and poly(ADP-ribose) (PAR) binding. These numerous
      functions can be attributed to the diversity in BRCT domain structure and
      architecture, where domains can exist as isolated single domains or assemble into
      higher order homo- or hetero- domain complexes. In this review, we incorporate
      recent structural and biochemical studies to demonstrate how structural features
      allow single and tandem BRCT domains to attain a high degree of functional
      diversity.

PMID- 21734460
TI  - A phosphatase turns aggressive: the oncogenicity of Cdc14B.

PMID- 21734459
TI  - Siah1/SIP regulates p27(kip1) stability and cell migration under metabolic
      stress.
AB  - p27(kip1) has been implicated in cell cycle regulation, functioning as an
      inhibitor of cyclin-dependent kinase activity. In addition, p27 was also shown to
      affect cell migration, with accumulation of cytoplasmic p27 associated with tumor
      invasiveness. However, the mechanism underlying p27 regulation as a cytoplasmic
      protein is poorly understood. Here we show that glucose starvation induces
      proteasome-dependent degradation of cytoplasmic p27, accompanied by a decrease in
      cell motility. We also show that the glucose limitation-induced p27 degradation
      is regulated through an ubiquitin E3 ligase complex involving Siah1 and
      SIP/CacyBP. SIP (-/-) embryonic fibroblasts have increased levels of cytosolic
      p27 and exhibit increased cell motility compared to wild-type cells. These
      observations suggest that the Siah1/SIP E3 ligase complex regulates cell motility
      through degradation of p27.

PMID- 21734461
TI  - GM130: new insights into oocyte asymmetric division.

PMID- 21734462
TI  - c-Met-Akt pathway-mediated enhancement of inhibitory c-Raf phosphorylation is
      involved in vitamin K1 and sorafenib synergy on HCC growth inhibition.
AB  - Sorafenib is an FDA-approved agent for treatment of human hepatocellular
      carcinoma (HCC), but tumor shrinkage is minor. We therefore developed a strategy
      to combine K vitamins with sorafenib to treat HCC, and found that this
      combination enhanced sorafenib-induced HCC cell growth inhibition. To explore the
      mechanisms involved, we examined the role of Raf kinase, since both vitamins K
      and sorafenib were reported to inhibit tumor cell growth via Raf signaling
      pathway. We found that whereas lower concentration of vitamin K1 (25 MUM) or
      sorafenib (2.5 MUM) alone slightly induced c-Raf phosphorylation at both Ser-43
      and Ser-259, combination vitamin K1 plus sorafenib resulted in strong c-Raf
      phosphorylation at these two serine residues. A Raf kinase activity assay
      confirmed that combination vitamin K1 plus sorafenib had a synergistic inhibitory
      effect on it. Since c-Raf phosphorylation at Ser-43 and Ser-259 can be regulated
      by either PKA or Akt kinase, we examined the effects of both vitamin K1 and
      sorafenib on their phosphorylation. Although vitamin K1 or sorafenib alone
      induced PKA phosphorylation, no enhanced phosphorylation effects on PKA were
      found using this combination. However, vitamin K1 enhanced sorafenib-induced c
      Met phosphorylation at Tyr-1349, a DEP-1 protein phosphatase acting site, and
      consequently induced phosphorylation of PI3K-Akt. Both PI3K inhibitor Ly294002 as
      well as dominate negative Akt plasmid transfection antagonized vitamin K1 plus
      sorafenib actions on c-Raf phosphorylation and cell growth inhibition, suggesting
      that c-Met-PI3K-Akt signaling pathway mediated inhibitory c-Raf phosphorylation
      may play a central role in vitamin K1 plus sorafenib synergy in inhibiting HCC
      cell growth.

PMID- 21734463
TI  - An RNA G-quadruplex in the 3' UTR of the proto-oncogene PIM1 represses
      translation.
AB  - We have identified a conserved G-quadruplex forming sequence in the 3'
      untranslated region (UTR) of the proto-oncogene PIM1. Circular dichroism and
      thermal denaturation studies revealed that the PIM1 mRNA guanine-rich sequence
      forms a highly stable intramolecular G-quadruplex structure. Reporter gene assay
      demonstrated that the PIM1 RNA G-quadruplex represses translation. It is the
      first experimental evidence of an RNA G-quadruplex structure located in the 3'
      UTR that may act as posttranscriptional regulator.

PMID- 21734464
TI  - Wasting lives: the effects of toxic waste exposure on health. The case of
      Campania, Southern Italy.
AB  - Three decades of illegal practices of waste dumping and consequent environmental
      abuse have made the Campania region of Southern Italy a unique case in the
      context of waste-related health outcomes. Scientific evidence is mounting in
      support of a significant increase in cancer mortality and malformation occurrence
      in specific areas of the Campania region, where improper waste management and
      illegal waste trafficking have been repeatedly documented. However, the currently
      available evidence suffers from limitations mainly due to study design, lack of
      consideration of confounders and quality of the exposure data. Recent economic
      studies have shown the economic benefits of reclaiming toxic waste sites in
      Campania. Future perspectives include the adoption of different study designs,
      use of biomarkers and a molecular approach. Current knowledge, both scientific
      and economic, might be of help in orienting the short and long term governmental
      policy on waste related health outcomes at a regional level.

PMID- 21734465
TI  - Intra-dermal administration of rabies vaccines in developing countries: at an
      affordable cost.
AB  - Rabies is a virtually 100% fatal acute viral encephalitis. Rabies occurs in more
      than 150 countries and territories. Globally there are 17.4 million animal bite
      cases and more than 55,000 deaths annually. India's 20,000 deaths accounts for
      36% of global and 65% of the Asian (31,000) deaths. The Intradermal Rabies
      Vaccine (IDRV) was first started in Thailand in 1984. In 1992, World Health
      Organization approved it for use in developing countries which face a shortage of
      rabies vaccine due to paucity of funds. Vaccines like Purified Vero cell vaccine
      (PVRV), Purified chick embryo cell vaccine (PCECV) and Human diploid cell vaccine
      (HDCV) that can be injected by the intradermal route for Post Exposure
      Prophylaxis as approved by WHO. The regimen approved by the WHO/DCGI India is the
      Updated Thai Red Cross Regimen, which involves injection of 0.1 mL of
      reconstituted vaccine per ID site and on two such ID site per visit on Days 0, 3,
      7 and 28 (2-2-2-0-2). All reconstituted vaccine unused at the end of 6-8 h must
      be discarded. The ID route is ideal in terms of economic benefits, safety and
      efficacy. This reduces the cost of vaccination by about 68%, which is clearly an
      attractive option for resource-starved countries like India.

PMID- 21734466
TI  - Summary of effectiveness and impact of rotavirus vaccination with the oral
      pentavalent rotavirus vaccine: a systematic review of the experience in
      industrialized countries.
AB  - The pentavalent rotavirus (RV) vaccine RotaTeqTM has been available in
      industrialized countries since 2006. Several studies have been conducted to
      evaluate the benefit of RV vaccination under routine conditions of use. A
      systematic review of all publicly available data from RotaTeqTM vaccine
      effectiveness and vaccination-impact studies in the USA, Europe and Australia
      between 2006 and February 2010 was undertaken. Depending on the population
      studied, effectiveness of up to 100% (95% confidence interval 85-100%) associated
      with decreased hospitalizations for RV gastroenteritis (RVGE) was seen.
      Vaccination-impact studies demonstrated that the burden of RVGE has been reduced
      significantly since the introduction of RV vaccination. Evidence included
      reductions in healthcare utilization due to RVGE (hospitalizations and emergency
      department visits reduced by up to 90%), reductions in the magnitude and duration
      of the RV season as assessed by laboratory testing for RV, and the possible
      induction of herd immunity.

PMID- 21734467
TI  - Early clinical experience with a candidate meningococcal B recombinant vaccine
      (rMenB) in healthy adults.
AB  - BACKGROUND: The development of a broadly protective vaccine against meningococcal
      serogroup B is a well-recognized public health need. Whole-genome sequencing was
      used to identify meningococcal surface proteins that are conserved across
      strains. These proteins were incorporated into two investigational vaccines.
      METHODS: Three randomized studies were performed to evaluate a three-component
      recombinant meningococcal serogroup B vaccine (rMenB) and rMenB plus outer
      membrane vesicles from the Norwegian outbreak strain 44/76 (rMenB+OMVNW).
      Participants were randomized to receive 3 or 4 doses of rMenB or rMenB+OMVNW or
      control vaccines and provided sera for exploratory immunogenicity testing against
      a panel of meningococcal serogroup B strains. A booster dose was administered 12
      months after the initial primary series in one of the studies. The control cohort
      received a licensed quadrivalent meningococcal polysaccharide vaccine against
      serogroups A, C, W-135 and Y as well as hepatitis B vaccine as safety
      comparators. Solicited reactions within 7 days of any vaccination and adverse
      events throughout the studies were recorded. RESULTS: One hundred four
      participants enrolled into the clinical trials. Both rMenB and rMenB+OMVNW
      induced immune responses to multiple serogroup B strains in the majority of
      participants. Compared with rMenB, rMenB+OMVNW appeared somewhat more immunogenic
      and reactogenic; the study was not adequately powered for statistical assessment
      of these small differences. Both investigational vaccines were more reactogenic
      than the licensed vaccines. Few vaccinees discontinued any study due to
      reactogenicity to any study vaccine administered. CONCLUSION: Based on the
      immunogenicity and reactogenicity results in these participants, both rMenB and
      rMenB+OMVNW were promising candidates for further investigation.

PMID- 21734468
TI  - Estimating potential demand and supply of dengue vaccine in Brazil.
AB  - Dengue is endemic in Brazil. Several dengue vaccine candidates, including one at
      the Butantan Institute in Sao Paulo, are being evaluated in clinical trials and
      may be licensed in several years. This study estimates the potential doses of
      dengue vaccine needed in Brazil under different scenarios in the first 5 years
      after vaccine introduction. Estimates were based on 2015-2022 country population
      projections. An estimated country population of 200-209 million with an annual
      3.3-3.5 million cohort in the 12 to 23 month age group was included in the
      analysis. Computations were made for vaccines requiring one, two and three doses.
      A total of 7.8-62.9 million doses would be needed for only routine vaccination of
      12-23 months cohort in first five years with different vaccination schedules. A
      combination of country-wide routine 12-23 month-old vaccination plus catch-up
      vaccination of individuals up to 40 years age is an appropriate strategy to
      control dengue. For this combination strategy, 129-425 million doses would be
      needed in the first five years after introduction. If vaccination is not provided
      to areas with low incidence of dengue, an estimated 108-360 million doses would
      be needed. This study provides a range of vaccine uptake estimates under
      different scenarios based on disease epidemiology. Actual demand and uptake will
      depend on the country vaccine introduction policy and strategies, vaccine supply
      capacity, cost, and vaccine profile. We consider one option based on the
      availability of vaccine from different sources. A more advanced vaccine uptake
      model based on estimates of vaccine impact under various scenarios should be
      developed.

PMID- 21734469
TI  - HDV-like self-cleaving ribozymes.
AB  - HDV ribozymes catalyze their own scission from the transcript during rolling
      circle replication of the hepatitis delta virus. In vitro selection of self
      cleaving ribozymes from a human genomic library revealed an HDV-like ribozyme in
      the second intron of the human CPEB3 gene and recent results suggest that this
      RNA affects episodic memory performance. Bioinformatic searches based on the
      secondary structure of the HDV/CPEB3 fold yielded numerous functional ribozymes
      in a wide variety of organisms. Genomic mapping of these RNAs suggested several
      biological roles, one of which is the 5' processing of non-LTR retrotransposons.
      The family of HDV-like ribozymes thus continues to grow in numbers and biological
      importance.

PMID- 21734471
TI  - The R2 retrotransposon RNA families.
AB  - Analysis of the R2 retrotransposons from multiple silkmoth and fruitfly species
      have revealed three segments that contain conserved RNA secondary structures.
      These conserved structures play important roles in the propagation of the R2
      element, including R2 RNA processing and transposon integration into the host
      genome as well as a likely role in translation. Two of the structured regions
      comprise protein binding sites: one is located in the 3' UTR and the other is in
      the 5' UTR close to the putative start of the R2 open reading frame (ORF). The 3'
      structure was deduced from chemical mapping and sequence comparison. The 5'
      structure was determined using a combination of chemical mapping, oligonucleotide
      binding, NMR and sequence analysis and contains an unusual pseudoknot structure.
      The third structure occurs at the 5' end of the R2 RNA and is responsible for
      self-cleavage of the 5' end of the element from a 28S ribosomal RNA co
      transcript. A structure for this fragment was proposed based on motif searching
      and sequence comparison. There is remarkable similarity in sequence and structure
      to the hepatitis delta virus (HDV) ribozyme. Seed alignments for the 5' structure
      and the R2 ribozyme, containing representative sequences and consensus
      structures, have been submitted to the Rfam database.

PMID- 21734472
TI  - Impact of adding enfuvirtide to the predictive value of the darunavir genotypic
      resistance score.

PMID- 21734470
TI  - Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis:
      the seed and soil also needs "fertilizer".
AB  - In 1889, Dr. Stephen Paget proposed the "seed and soil" hypothesis, which states
      that cancer cells (the seeds) need the proper microenvironment (the soil) for
      them to grow, spread and metastasize systemically. In this hypothesis, Dr. Paget
      rightfully recognized that the tumor microenvironment has an important role to
      play in cancer progression and metastasis. In this regard, a series of recent
      studies have elegantly shown that the production of hydrogen peroxide, by both
      cancer cells and cancer-associated fibroblasts, may provide the necessary
      "fertilizer," by driving accelerated aging, DNA damage, inflammation and cancer
      metabolism, in the tumor microenvironment. By secreting hydrogen peroxide, cancer
      cells and fibroblasts are mimicking the behavior of immune cells
      (macrophages/neutrophils), driving local and systemic inflammation, via the
      innate immune response (NFkappaB). Thus, we should consider using various
      therapeutic strategies (such as catalase and/or other anti-oxidants) to
      neutralize the production of cancer-associated hydrogen peroxide, thereby
      preventing tumor-stroma co-evolution and metastasis. The implications of these
      findings for overcoming chemo-resistance in cancer cells are also discussed in
      the context of hydrogen peroxide production and cancer metabolism.

PMID- 21734473
TI  - Wilms tumor gene 1 (WT1) is a prognostic marker in high-grade uterine sarcoma.
AB  - INTRODUCTION: Wilms tumor gene 1 (WT1) contributes to uterine sarcoma tumor
      biology. In this study, we aimed to clarify the prognostic value of WT1. METHODS:
      A retrospective clinical and histopathological review of 71 women with high-grade
      uterine sarcoma (leiomyosarcoma [n = 24], undifferentiated sarcoma [n = 9]), and
      carcinosarcoma (n = 38) was performed. Patients were followed up for at least 12
      months. Wilms tumor gene 1 expression was determined by immunohistochemistry.
      Data on recurrence (progression-free survival) and overall survival (OS) were
      available for all patients. Univariate and multivariate analyses of WT1
      expression were carried out using Kaplan-Meier curves and Cox regression,
      respectively. RESULTS: Forty-nine (69%) tumors were WT1 positive. Forty-seven
      (66%) patients died of the disease, with a median OS time of 22 months. Wilms
      tumor gene 1 was a predictor of survival in the univariate analysis: the hazard
      ratio of WT1 positivity was 2.44 (95% confidence interval, 1.34-4.71) for
      progression-free survival and 2.48 (95% confidence interval, 1.26-4.90) for OS.
      Multivariate analysis including stage, age, tumor size, and sarcoma subtype
      identified only stage and WT1 positivity as independent prognostic markers for
      survival. CONCLUSIONS: The identification of WT1 as a prognostic marker confirms
      its role in high-grade uterine sarcoma and carcinosarcoma tumor biology.

PMID- 21734474
TI  - Evolution in endometrial cancer: evidence from an immunohistochemical study.
AB  - BACKGROUND: It is poorly described how endometrial cancer biology changes during
      tumor evolution. We hypothesize that characterization of molecular targets in
      recurrent lesions is more relevant for targeting treatment. METHODS: Paired
      biopsies from primary and recurrent endometrial cancer tumors (n = 85) were
      stained immunohistochemically for the following proteins: estrogen receptor (ER),
      progesterone receptor (PR), stathmin (correlating with phosphatidylinositol 3
      kinase activity), HER-2/neu, WT1 (Wilms tumor gene 1), phospho-mammalian target
      of rapamycin (p-mTOR), and p53. Each tumor was scored, using a semiquantitative
      and subjective grading system. Discordance, a change in expression between
      primary and recurrent tumor, was defined as >= 2 step change; concordance was <=
      1 step change. The frequency of change was correlated with established prognostic
      markers in endometrial cancer. RESULTS: Fifty-six patients (67%) were diagnosed
      with endometrioid carcinoma, 23 (27%) with serous/clear cell carcinoma. A change
      in expression between primary and recurrent tumor was noted in 7% to 31% of
      patients for ER, PR, stathmin, HER-2/neu, WT1, p-mTOR, and p53. Concordant
      positive cases for PR were significantly correlated with stage, tumor grade, and
      histological subtype. Expression of ER, p53, and p-mTOR in cytoplasm in the
      recurrent tumor correlated significantly with survival. CONCLUSIONS: Endometrial
      cancer biology changes over time. The decision on targeted treatment should
      preferably be based on recurrent tumor characteristics.

PMID- 21734475
TI  - Remembrance of William Wei-Lien Shaw, MD (1942-2010).

PMID- 21734476
TI  - Dr. Shaw.

PMID- 21734478
TI  - Images in plastic surgery: the anatomy of macrovascular arteriovenous shunts and
      implications for abdominal wall free flaps.
AB  - With the increasing use of preoperative imaging of the abdominal vasculature
      prior to free flaps based on the abdominal wall, the identification of a
      previously undescribed anatomic structure has, that of large-vessel (macroscopic)
      arteriovenous communications, has emerged. These macrovascular arteriovenous
      shunts are observed in most patients, and provide a communication between the
      arterial perforators of the deep inferior epigastric artery and the superficial
      inferior epigastric vein. These communications provide vascular shunting
      occurring prior to capillary filling and have potentially profound clinical
      implications and therapeutic possibilities in a range of medical and surgical
      conditions. Although these have been demonstrated previously on computed
      tomographic angiography imaging, their macroscopic and microscopic anatomy has
      not been described. We present images in vivo, ex vivo, and histologically to
      highlight their anatomic features.

PMID- 21734480
TI  - Intraoperative measurements of harvestable septal cartilage in rhinoplasty.

PMID- 21734481
TI  - Proposed pattern of platelet and platelet distribulogram change from automated
      complete blood count in dengue infection: a new pattern based on known concepts.

PMID- 21734482
TI  - Position of tirofiban in ST segment elevation myocardial infarction treatment:
      more than an adjunctive therapy.

PMID- 21734484
TI  - Bibliography--editors' selection of current word literature.

PMID- 21734483
TI  - Pressure-induced interlamellar stromal keratitis after laser in situ
      keratomileusis.
AB  - PURPOSE: To describe a patient with interlamellar stromal keratitis induced by
      increased intraocular pressure (IOP) [Pressure-induced interlamellar stromal
      keratitis (PISK)] after laser in situ keratomileusis (LASIK) surgery. METHODS:
      Case report and review of the literature. RESULTS: We report a case of
      interlamellar stromal keratitis induced by increased IOP after LASIK surgery. A
      42-year-old man presented with persistent interface haze after uneventful LASIK.
      The patient described onset of decreased visual acuity after the first 2
      postoperative weeks, failed to improve with high-dose topical steroid drops, and
      had significantly elevated IOP values up to 48 mm Hg. IOP was resistant to
      maximal topical antiglaucomatous therapy. The patient showed both improvement in
      visual acuity and decrease in interface haze after discontinuation of topical
      steroids and lowering of IOP by both topical and systemic treatment. Slit-lamp
      optical coherence tomography ruled out a fluid accumulation in the interface.
      CONCLUSIONS: PISK appears clinically almost identical to diffuse lamellar
      keratitis after LASIK. It is important to measure the IOP and be suspicious when
      a diffuse interface haze occurs after the first postoperative week, is resistant
      to or even exacerbates in response to an increase in topical steroid treatment,
      and is not associated with other causative events. Slit-lamp optical coherence
      tomography is a valuable tool that allows differentiation between space-occupying
      interface fluid collection and non-space-occupying interface fluid collection to
      avoid falsely low or normal IOP measurements in PISK.

PMID- 21734486
TI  - Nutritional pharmacology in surgery and critical care: 'you must unlearn what you
      have learned'.
AB  - PURPOSE OF REVIEW: This review highlights the rapidly evolving field of
      'pharmaconutrition' by discussing the mechanistic and clinical data for calorie
      delivery and nutrients shown to improve outcome in surgical and ICU care. RECENT
      FINDINGS: International survey data reveals patients in acute care settings
      receive approximately 50% of calories/protein they are prescribed. This is, in
      part, due to the archaic practice of patients remaining nil per os
      postoperatively until return of bowel sounds. We also know certain nutrients
      serve as pharmacologic agents and improve clinically relevant outcomes. Thus,
      larger therapeutic doses of specific nutrients may be required to replace acute
      deficiencies brought on by specific injury states. Specifically, arginine can
      reduce postsurgical infection 40% as shown in over 30 trials of more than 3200
      patients. Glutamine and fish oil have been shown to reduce mortality in general
      critical care and acute respiratory distress syndrome patients, respectively.
      SUMMARY: We believe the future of surgical and ICU nutrition will involve
      administering specific pharmaconutrients as separate components, much like drugs
      are given. The current use of clinical pharmacology, molecular biology, and
      clinical research principles in the study of pharmaconutrients should yield
      answers on how to administer the right nutrients, in the right doses, at the
      right time in sick patients.

PMID- 21734488
TI  - Current Opinion in Critical Care was launched in 1995.

PMID- 21734487
TI  - Bibliography. Drugs in anesthesia. Current world literature.

PMID- 21734489
TI  - Noninvasive hemodynamic monitoring in the emergency department.
AB  - PURPOSE OF REVIEW: Emergency department patients are frequently undifferentiated,
      need accurate risk assessment and stratification, and are time-critical in their
      need for diagnosis and resuscitation. Valid, noninvasive hemodynamic monitoring
      modalities are essential to differentiate high from low risk patients, and to
      perform goal-directed management. This review analyses recent literature, which
      describes innovation in the range of noninvasive monitoring tools and places them
      in the emergency medicine context. RELEVANT FINDINGS: A range of noninvasive
      measures of hemodynamic status are both commonly used, or are in the research and
      development phase. Pulse oximetry waveforms, electrocardiogram-based heart rate
      variability, Doppler and B-mode ultrasound, echocardiography, transthoracic
      bioimpedance, pressure pulse waveform analysis and near-infrared spectroscopy all
      have potential value in diagnosis and monitoring of hemodynamics, particularly
      used to explore autonomic nervous system control of cardiovascular function and
      by extension the early phases of compensation for illness and injury. Noninvasive
      techniques coupled with advances in data visualization and pattern recognition
      bring the potential for revolution to emergency department hemodynamic
      monitoring. SUMMARY: Noninvasive measures of hemodynamic status and function are
      increasingly being used, although much still remains in the research domain.
      Noninvasive measures may not only offer similar variables to traditional vital
      signs, but add a new dimension of hemodynamic descriptors.

PMID- 21734490
TI  - Perioperative pulmonary complications.
AB  - PURPOSE OF REVIEW: This article reviews current concepts in perioperative
      pulmonary management. RECENT FINDINGS: Preoperative risk assessment tools for
      perioperative pulmonary complications (POPCs) are evolving for both children and
      adults. Intraoperative management strategies have a demonstrable effect on
      outcomes. Late POPCs may be preceded by clinical signs. SUMMARY: POPCs are common
      and lead to significant resource utilization. Optimal POPC risk mitigation must
      span all phases of surgical care. Preoperative assessment may identify patients
      at risk and effectively lower their risk by identifying targeted interventions.
      Intra-operative strategies impact postoperative outcome. POPCs continue to be a
      concern for several days postoperatively. We review the current literature on
      this broad subject with a focus on implementable interventions for the clinician.

PMID- 21734491
TI  - Perioperative glycemic management in 2011: paradigm shifts.
AB  - PURPOSE OF REVIEW: The publication of Van den Berghe's landmark study in 2001
      supported the use of intensive insulin therapy (IIT) to target normoglycemia in
      the critically ill and triggered a new era in glycemic management in the
      perioperative period and in the ICU. In 2009, the normoglycemia in intensive care
      evaluation-survival using glucose algorithm regulation (NICE-SUGAR) trial
      demonstrated increased mortality and incidence of hypoglycemia in patients
      managed with IIT, resulting in a shift toward higher blood glucose targets in
      this patient population. This review distills clinically pertinent principles
      from the related literature published in the months since the NICE-SUGAR trial.
      RECENT FINDINGS: A target blood glucose level in the acute care setting supported
      by many of the pertinent societies and frequently quoted in the literature is 140
      180 mg/dl. Hyperglycemia, hypoglycemia, and glucose variability are detrimental.
      Accurate and efficient glucose monitoring devices are essential. Insulin infusion
      protocols (IIPs) employed to achieve desired blood glucose targets must be
      individualized and validated for the ICU and institution in which they are being
      implemented. SUMMARY: Appropriate glycemic management in the acute care setting
      can be achieved by targeting a reasonable blood glucose range and employing
      specific and institutionally validated IIPs.

PMID- 21734492
TI  - Current world literature.

PMID- 21734494
TI  - Genetics of Parkinson's disease and essential tremor.
AB  - PURPOSE OF REVIEW: This review summarizes some key findings of the past few years
      on the genetics of the two common movement disorders Parkinson's disease and
      essential tremor. RECENT FINDINGS: Within the last two years, genome-wide
      association (GWA) analyses have revealed a number of novel low-risk
      susceptibility variants for Parkinson's disease, among them HLA-DRB5, BST1,
      ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R) and have confirmed LINGO1 as
      risk factor for essential tremor. The identification of copy number variations in
      the Parkin gene in healthy control individuals suggests no major role of these
      variations in late onset Parkinson's disease. Drosophila studies on Parkin and
      Pink1 have uncovered a role in the mitochondrial quality control pathway in the
      pathogenesis of the disease. LRRK2 has been found to interact with the microRNAs
      processing protein Argonaut, thereby affecting protein translation. Notably,
      despite the high familial risk for essential tremor no high-risk gene has been
      found to date. The possibility of a nonmendelian transmission in some cases is
      discussed. SUMMARY: GWA studies and positional cloning approaches have led to the
      identification of a number of risk genes for Parkinson's disease, which give
      novel insights into pathogenic pathways of the disease. In contrast, our
      knowledge of the genetics of essential tremor is scarce. Except for LINGO1, no
      other risk gene has so far been identified. New technologies such as next
      generation high throughput sequencing might help to identify more risk genes.

PMID- 21734495
TI  - Update on degenerative ataxias.
AB  - PURPOSE OF REVIEW: Degenerative ataxias are a heterogeneous group of disorders
      that are clinically characterized by progressive ataxia. They can be subdivided
      into three major groups: the acquired ataxias, which are due to exogenous or
      endogenous nongenetic causes, the hereditary ataxias, and the nonhereditary
      degenerative ataxias. On the basis of a review of the literature published in
      2009 and 2010, this review gives an update of the most recent developments in the
      field of ataxia. RECENT FINDINGS: Using advanced methods of molecular genetic
      analysis, novel genes for recessive and dominant ataxias were identified. Recent
      imaging studies in dominantly inherited spinocerebellar ataxias (SCAs) focussed
      on the analysis of connectivity in the brain. Novel clinical assessment methods
      were developed and validated in large patient cohorts. Although a phase 3 trial
      of idebenone in Friedreich ataxia (FRDA) failed, a smaller phase 2 trial of
      riluzole in a mixed population of ataxia patients suggested a possible antiataxic
      action of this compound. SUMMARY: Recent molecular advances underline the
      diversity of degenerative ataxias. With the progress in the development of
      clinical assessment methods for ataxia, the methodological requirements to run
      large interventional trials are now met.

PMID- 21734496
TI  - Forensic neurosciences: from basic research to applications and pitfalls.
AB  - PURPOSE OF REVIEW: In recent years, there has been growing interest in the
      application of genetic and neuroscientific methods to the investigation of the
      criminal mind. Here we summarize the results of recent studies and discuss their
      potential implications for the criminal system. RECENT FINDINGS: The results of
      studies published so far have implications for theoretical aspects of the law.
      For example, a series of studies have indicated that conscious sense of volition
      may not be a driving force in the initiation of willed behavior but rather may
      arise as a consequence of such behavior. According to some, this challenges the
      very notion of conscious will on which the criminal system is based. The results
      also have implications for practical aspects of the law. For instance, genetic
      and neuroscientific methods may provide objective, biological data which can be
      used to reduce controversy in forensic psychiatric evaluations of mental insanity
      and minimize errors in detecting malingering. Another potential practical
      application is lie and memory detection, which at present appears to be
      susceptible to countermeasures. SUMMARY: Genetic and neuroimaging techniques may
      provide information which, when considered in combination with other sources of
      evidence, might prove useful in advancing knowledge about mens rea.

PMID- 21734497
TI  - Recent progress in high-resolution functional MRI.
AB  - PURPOSE OF REVIEW: For functional MRI (fMRI), as for any imaging technique, the
      higher the spatial resolution, the more the details it can reveal. This review
      will discuss the factors restricting the spatial resolution of fMRI, describe
      high-resolution fMRI (HR-fMRI) applications in neuroscience and outline a few
      research areas for future HR-fMRI studies. RECENT FINDINGS: HR-fMRI has been
      successfully used to map fine cortical architectures and reveal cortical laminar
      structures and subcortical structures. HR-fMRI has also played important roles in
      resolving controversies regarding modular representations in the ventral visual
      pathway and interpretations of multivariate pattern analysis results. SUMMARY:
      Real-time HR-fMRI as well as high-resolution anatomical MRI may emerge as
      indispensable tools for surgical planning, diagnosis of neurological diseases and
      targeting of deep brain stimulation.

PMID- 21734498
TI  - Current world literature.

PMID- 21734500
TI  - Current status of human oocyte and embryo cryopreservation.
AB  - PURPOSE OF REVIEW: To summarize recent advances in oocyte and embryo
      cryopreservation techniques and outcomes. RECENT FINDINGS: Vitrification is
      gradually replacing slow freezing due to a better survival rate after thawing.
      Most units use vitrification for both oocyte and blastocyst cryopreservation, as
      these two biological structures did not perform very well with slow freezing
      technique. Basic experiments show that cellular damage seems lower after
      vitrification. Taken all together, this is helping vitirification to be expanding
      rapidly, and new clinical indications are being incorporated as well (i.e.,
      fertility preservation). SUMMARY: Cryopreservation has been used as a complement
      to IVF, and recent publications indicate that pregnancy rates achieved with
      frozen oocytes and embryos are comparable with those achieved in fresh cycles.
      Multiple publications studying oocyte and embryo physiology during
      cryopreservation have been published recently; however, larger studies are needed
      to verify the efficacy of new cryopreservation techniques. Vitrification is a
      simple and robust technique that is being incorporated into the majority of IVF
      units, mainly for oocyte and blastocyst cryopreservation.

PMID- 21734501
TI  - Laparoscopic ureteral repair in gynaecological surgery.
AB  - PURPOSE OF REVIEW: To review laparoscopic surgery in the treatment options for
      ureteral lesions in gynaecological surgery. RECENT FINDINGS: Laparoscopic
      treatment of ureteral injuries has been increasingly reported over the past
      years. Treatment has progressively shifted from ureteroneocystostomy performed by
      laparotomy to less invasive treatment options such as ureteral stenting or
      dilatation in case of stricture, stenting under laparoscopic guidance and
      laparoscopic stitching of lacerations, laparoscopic ureteral reanastomosis or
      laparoscopic ureteroneocystostomy for transections. Deep endometriosis surgery of
      an associated hydronephrosis is associated with a high incidence of ureteral
      lesions making preoperative stenting desirable in order to facilitate the
      eventual repair, while avoiding the more problematic insertion of a stent after a
      lesion is made.The available data confirm the excellent outcome of stenting
      obstructive lesions. When stenting proves difficult or in case of a ureteral
      leakage, laparoscopic aided stenting is strongly suggested, in order to avoid
      further damage while permitting simultaneous repair if necessary. Laparoscopic
      suturing of a laceration over a stent is clearly superior to stenting only.
      Results of ureteral reanastomosis of a transected ureter vary from 88 to 100%; an
      occasional subsequent stenosis can be treated with dilatation. Bladder
      reimplantation has become feasible by laparoscopy and results seem promising.
      Laparoscopic bladder reimplantation is suggested as the method of choice in case
      of failure of a previous laparoscopic treatment. SUMMARY: Data strongly support
      laparoscopy as the method of choice for the management of ureteral lesions.

PMID- 21734502
TI  - Current world literature.

PMID- 21734503
TI  - Health services research: what is it and what has it done for anaesthesia and
      critical care?

PMID- 21734504
TI  - A hypothesis to explain the high prevalence of pseudo-cholinesterase deficiency
      in specific population groups.

PMID- 21734505
TI  - Guidelines on non-anaesthesiologist administration of propofol for
      gastrointestinal endoscopy: a double-edged sword.

PMID- 21734507
TI  - Perspectives on suicide and traumatic brain injury.

PMID- 21734508
TI  - A guide for the assessment and treatment of suicidal patients with traumatic
      brain injuries.
AB  - People with traumatic brain injuries (TBIs) are at elevated risk for suicide.
      Postinjury cognitive limitations, personality factors, and psychological problems
      may independently or in conjunction with preinjury correlates contribute to
      suicidal thoughts and behaviors. Rehabilitation practitioners can best serve the
      needs of this high-risk population by increasing their knowledge and competence
      in evidence-informed approaches to suicide prevention. This article provides a
      review of suicide nomenclature, epidemiology, risk and protective factors, as
      well as evidence-informed assessment, management, and treatment practices for
      suicidal patients. The science of clinical practice in the area of rehabilitation
      and suicide prevention is in its infancy. Practitioners who provide treatment for
      suicidal patients with TBI are encouraged to adapt and individualize existing
      evidence-informed suicide assessment and prevention practices for implementation
      within their settings. Each patient with a TBI who endorses suicidal thoughts
      and/or behaviors presents a complex array of clinical challenges associated with
      the nature of his or her brain injury, preinjury, and postinjury functioning.
      Clinical as well as research recommendations are provided in the context of an
      understanding of such challenges and an overriding objective of minimizing
      suicide risk during the recovery process and maximizing treatment gains.

PMID- 21734509
TI  - Suicide and traumatic brain injury among individuals seeking Veterans Health
      Administration services.
AB  - OBJECTIVE: To examine associations between history of traumatic brain injury
      (TBI) diagnosis and death by suicide among individuals receiving care within the
      Veterans Health Administration (VHA). METHOD: Individuals who received care
      between fiscal years 2001 to 2006 were included in analyses. Cox proportional
      hazards survival models for time to suicide, with time-dependent covariates, were
      utilized. Covariance sandwich estimators were used to adjust for the clustered
      nature of the data, with patients nested within VHA facilities. Analyses included
      all patients with a history of TBI (n = 49626) plus a 5% random sample of
      patients without TBI (n = 389053). Of those with a history of TBI, 105 died by
      suicide. Models were adjusted for demographic and psychiatric covariates.
      RESULTS: Veterans with a history of TBI were 1.55 (95% confidence interval [CI],
      1.24-1.92) times more likely to die by suicide than those without a history of
      TBI. Analyses by TBI severity were also conducted, and they suggested that in
      comparison to those without an injury history, those with (1) concussion/cranial
      fracture were 1.98 times more likely (95% CI, 1.39-2.82) to die by suicide and
      (2) cerebral contusion/traumatic intracranial hemorrhage were 1.34 times more
      likely (95% CI, 1.09-1.64) to die by suicide. This increased risk was not
      explained by the presence of psychiatric disorders or demographic factors.
      CONCLUSIONS: Among VHA users, those with a diagnosis of TBI were at greater risk
      for suicide than those without this diagnosis. Further research is indicated to
      identify evidence-based means of assessment and treatment for those with TBI and
      suicidal behavior.

PMID- 21734510
TI  - Suicidal ideation following traumatic brain injury: prevalence rates and
      correlates in adults living in the community.
AB  - OBJECTIVE: To explore the rates of suicidal ideation (SI) in a sample of
      community-dwelling adults with traumatic brain injury (TBI) and to assess the
      relationship between SI and demographic and injury characteristics, pre- and
      postinjury psychiatric history, and psychosocial functioning. PARTICIPANTS: Data
      were collected from a cohort study focused on health, psychosocial functioning,
      and community integration post-TBI (N = 356). Participants were individuals with
      mild to severe TBI living in the community. MEASURES: The Beck Depression
      Inventory II (BDI-II) was used to assess SI. Psychiatric functioning was assessed
      using the Structured Clinical Interview for Diagnostic and Statistical Manual of
      Mental Disorders (Fourth Edition) (DSM-IV) Axis I disorders (SCID-I), and
      psychosocial functioning was assessed using the Life-3, the Flanagan Scale of
      Unmet Needs, and the Bigelow Quality of Life Questionnaire. RESULTS: There were
      no differences in SI endorsement based on gender, age, race, income, education,
      injury severity, or length of time since injury. Those who met current criteria
      for a psychiatric diagnosis of depression, anxiety, or posttraumatic stress
      disorder reported SI more frequently. Those with SI reported significantly lower
      psychosocial functioning. CONCLUSION: Individuals with TBI from all demographic
      groups and with injuries of varying severity are at risk for SI and thus for
      emotional distress and suicidal behavior. Screening for SI is indicated in all
      individuals with TBI, particularly those with a history of premorbid substance
      misuse and concurrent mood and anxiety disorders. The importance of interventions
      to maximize social support and reduce social isolation is discussed.

PMID- 21734511
TI  - Neuroimaging correlates of traumatic brain injury and suicidal behavior.
AB  - INTRODUCTION: There is an urgent need to define the neurobiological and cognitive
      underpinnings of suicidal ideation and behavior in veterans with traumatic brain
      injury (TBI). Separate studies implicate frontal white matter systems in the
      pathophysiology of TBI, suicidality, and impulsivity. We examined the
      relationship between the integrity of major frontal white matter (WM) systems on
      measures of impulsivity and suicidality in veterans with TBI. METHODS: Fifteen
      male veterans with TBI and 17 matched healthy controls (HC) received clinical
      ratings, measures of impulsivity and MRI scans on a 3T magnet. Diffusion tensor
      imaging (DTI) data for the genu and cingulum were analyzed using Freesurfer and
      FSL. Correlations were performed for fractional anisotropy (FA) (DTI) values and
      measures of suicidality and impulsivity for veterans with TBI. RESULTS:
      Significantly decreased in FA values in the left cingulum (P = 0.02), and left (P
      = 0.02) and total genu (P = 0.01) were observed in the TBI group relative to
      controls. Measures of impulsivity were significantly greater for the TBI group
      and total and right cingulum FA positively correlated with current suicidal
      ideation and measures of impulsivity (P <0.03). CONCLUSION: These data
      demonstrate a significant reduction in FA in frontal WM tracts in veterans with
      mild TBI that was associated with both impulsivity and suicidality. These
      findings may reflect a neurobiological vulnerability to suicidal risk related to
      white matter microstructure.

PMID- 21734512
TI  - Suicide prevention after traumatic brain injury: a randomized controlled trial of
      a program for the psychological treatment of hopelessness.
AB  - OBJECTIVE: To evaluate the efficacy of a psychological treatment to reduce
      moderate to severe hopelessness after severe traumatic brain injury (TBI).
      METHOD: Randomized controlled trial. Participants were aged between 18 and 65
      years, experienced posttraumatic amnesia more than 1day and moderate to severe
      hopelessness (Beck Hopelessness Scale [BHS]) and/or suicide ideation.
      Intervention comprised a 20-hour manualized group cognitive behavior therapy
      program. Participants were randomly allocated using concealed allocation
      (treatment n = 8; wait-list n = 9); all remained in their allocated group.
      Outcome variables were collected by assessors blind to group allocation. RESULTS:
      No between-groups differences were observed on demographic, injury, cognitive,
      and psychosocial variables at baseline (time 1). A significant group-by-time
      interaction was found for BHS in the treatment group (F1,15 = 13.20, P = .002),
      reflecting a reduction in mean BHS scores between time 1 and time 2
      (posttreatment) with no main effects for group or time. At 3-month follow-up
      (time 3), the treatment gains were maintained or improved for 75% (6/8) of
      participants. Secondary outcome variables (suicide ideation, depression, social
      problem solving, self-esteem, hopefulness) displayed no significant group-by-time
      interactions or main effects. CONCLUSIONS: This trial provides initial evidence
      for the efficacy of a psychological intervention in reducing hopelessness among
      long-term survivors with severe TBI.

PMID- 21734513
TI  - Cholinergic dysfunction and cognitive impairment after traumatic brain injury.
      Part 2: evidence from basic and clinical investigations.

PMID- 21734514
TI  - Please, no more excuses.

PMID- 21734515
TI  - IV P.U.M.P. (Politically Useful Messages for Practicing Nurses).

PMID- 21734516
TI  - State of the society.

PMID- 21734517
TI  - 2010 financial report.

PMID- 21734518
TI  - Chief executive officer's message.

PMID- 21734519
TI  - Presidential address.

PMID- 21734520
TI  - A new approach to management of intravenous infiltration in pediatric patients:
      pathophysiology, classification, and treatment.
AB  - Intravenous (IV) infiltrations are problematic complications associated with
      hospitalization. Treatment methods vary greatly on the basis of physician
      judgment and institutional protocol, and uniform methods for effective prevention
      and economical treatment of IV infiltrations are necessary. Common in neonatal
      and infant patients, infiltration is frequently associated with cosmetic and
      functional complications. Medicolegal issues for physicians and institutions also
      accompany many cases of infiltration. This article discusses the pathophysiology
      of IV infiltrations. It also presents a new scale for IV infiltrations that more
      accurately reflects issues common to neonatal and pediatric patients and
      describes a novel, noninvasive treatment. A quantitative study of the decrease in
      morbidity after implementing this protocol will be conducted pending
      institutional approval.

PMID- 21734521
TI  - Prevention, assessment, and treatment of central venous catheter occlusions in
      neonatal and young pediatric patients.
AB  - Central venous catheter occlusions disrupt delivery of needed therapies to
      vulnerable neonatal and young pediatric patients. Nursing practices that minimize
      risk of catheter occlusion include proper infusion and flushing techniques.
      Treatment strategies vary on the basis of the source of the occlusion. Mechanical
      occlusions can often be resolved by altering the patient's position, correcting
      catheter kinks, or adjusting clamps. Occlusions caused by precipitation can be
      cleared through instillation of ethanol, hydrochloric acid, or sodium
      bicarbonate, depending on the chemistry of the infusates. Finally, the
      thrombolytic agent alteplase is recommended for treatment of catheter occlusion
      because of thrombus formation.

PMID- 21734522
TI  - Examining the effectiveness of 2 solutions used to flush capped pediatric
      peripheral intravenous catheters.
AB  - An evidence-based study examined the effectiveness of 2 solutions, heparin and
      normal saline, when used to flush capped pediatric peripheral intravenous (CPP
      IV) catheters. This experimental study assessed patency, redness, swelling,
      clotting, bruising, leakage, and patient pain after each intervention/flush.
      Study participants included 62 children (32 heparin and 30 normal saline) who had
      CPP IV catheters using 20-, 22-, or 24-gauge catheters. No statistically
      significant differences were found in IV catheter patency between children in the
      normal saline group and children in the heparin group. A postimplementation
      follow-up study with 30 patients who received normal saline only as a flush
      experienced no patency issues.

PMID- 21734530
TI  - Gallic acid inhibits the migration and invasion of A375.S2 human melanoma cells
      through the inhibition of matrix metalloproteinase-2 and Ras.
AB  - Melanoma is one of the most common cancers worldwide and its incidence has been
      increasing over the past few decades. Gallic acid (GA) can inhibit the growth of
      human cancer cells in vitro and in vivo. However, there is no available
      information to address the effects of GA on migration and invasion of human skin
      cancer cells. Matrix metalloproteinases (MMPs), zinc-dependent proteolytic
      enzymes, play an important role in the invasion, metastasis, and angiogenesis of
      cancer cells. Therefore, MMPs are one of the targets for agents to suppress and
      that could inhibit the migration and invasion of cancer cells. GA affected the
      viable A375.S2 cells by propidium iodide exclusion and flow cytometric analysis.
      Cell migration and invasion were investigated by Boyden chamber assay and we also
      determined the levels of protein and mRNA expression cell migration and invasion
      by gelatin zymography, western blotting, and real-time PCR assays. In this study,
      we examined the influence of GA on the protein levels and gene expression of MMP
      2 and MMP-9 and in-vitro migration and invasiveness of human melanoma cells. GA
      decreases the MMPs and associated signal pathway protein and MMPs mRNA levels in
      A375.S2 human melanoma cells. Our findings suggest that GA has antimetastatic
      potential by decreasing invasiveness of cancer cells. Moreover, this action of GA
      was involved in the Ras, p-ERK signaling pathways resulting in inhibition of MMP
      2 in A375.S2 human melanoma cells. These data, therefore, provide evidence for
      the role of GA as a potential cancer chemotherapeutic agent, which can markedly
      inhibit the invasive capacity of melanoma cells.

PMID- 21734531
TI  - A rare case of acute respiratory distress syndrome secondary to acute lithium
      intoxication.
AB  - Lithium carbonate is a widely administered antimanic drug used for the treatment
      of bipolar disorder, schizoaffective disorder, and depression. Despite the
      established clinical efficacy of lithium, its usage must be approached with
      caution due to its narrow therapeutic index. Lithium poisoning results in
      multisystem toxicity, and characteristic clinical manifestations are directly
      correlated to serum lithium concentration. We describe a rather rare but fatal
      side effect of lithium: acute respiratory distress syndrome (ARDS) in a 46-year
      old female on lithium for the treatment of bipolar disease. She was referred for
      generalized weakness, found in hemodynamic compromise, and had laboratory data
      significant for a lithium level of 3.3 mmole/L, needing emergent hemodialysis.
      Subsequently, she developed hypoxic respiratory failure requiring intubation. Her
      chest x-rays showed new bilateral pulmonary edema, the computed tomography scan
      showed extensive alveolar consolidation and V/Q scan of low probability for
      pulmonary embolism. She underwent 3 dialysis sessions and supportive care and was
      able to be extubated in 5 days. To our knowledge, 4 cases of ARDS after the onset
      of lithium toxicity have been documented. All patients presented with altered
      mental status at serum lithium levels ranging from 3.8 to 4.9 mmole/L and
      cardiogenic etiologies in addition to other likely causes of ARDS were ruled out
      in each case. The patients were treated with saline hydration (50%) or
      hemodialysis (50%), indicating that hemodialysis may be a permissive factor in
      lithium-associated ARDS development rather than a required component. Taken
      together, we believe that lithium is a likely culprit in the initiation of ARDS
      and propose the addition of ARDS to the family of clinical manifestations of
      severe lithium toxicity. 

PMID- 21734532
TI  - Liraglutide for the treatment of type 2 diabetes: a clinical update.
AB  - This review updates the pharmacology, efficacy, safety, and tolerability of
      liraglutide, a glucagon-like peptide 1 (GLP-1) analog approved for the treatment
      of type 2 diabetes (T2DM) in January 2010. MEDLINE was searched (May 2009-January
      1, 2011) for articles in English, using the terms liraglutide, NN2211, incretin
      mimetic, glucagon-like peptide (GLP)-1, and GLP-1 receptor agonist. Abstracts
      from key meetings (ADA 2009 and 2010, AACE 2010, EASD 2009, and EASD 2010) were
      also searched for relevant data. A GLP-1 analog with pharmacokinetic properties
      allowing once-daily administration via subcutaneous injection, liraglutide has
      shown clinical benefits when used as monotherapy or in combination. Liraglutide
      monotherapy has demonstrated efficacy in reducing hemoglobin A1c (A1C) and body
      weight, with low risk for hypoglycemic events. Liraglutide has also been studied
      in combination with metformin, glimepiride, and rosiglitazone for the treatment
      of T2DM. Extension studies within the Liraglutide Effects and Action in Diabetes
      clinical program have demonstrated the efficacy of liraglutide over 2 years of
      treatment. Overall, liraglutide has been shown to be well tolerated, with dose
      dependent nausea, vomiting, and diarrhea being the most commonly reported adverse
      events in clinical trials. Extended dosing periods have demonstrated the
      durability of response of liraglutide with respect to glycemic control, lack of
      weight gain, and blood pressure benefits. Compared with exenatide and
      sitagliptin, liraglutide seems to offer greater improvements in A1C, fasting
      plasma glucose, and body weight. Adverse events commonly associated with
      liraglutide in clinical trials included nausea and hypoglycemia. Emerging data
      suggest that liraglutide may be a useful option for patients with T2DM.

PMID- 21734533
TI  - Liposomal amphotericin B-induced hypotension leading to ST segment elevated
      myocardial infarction.
AB  - We hereby report a short case of 71-year-old gentleman who developed ST segment
      elevation myocardial infarction shortly after starting the infusion of liposomal
      amphotericin B for disseminated histoplasmosis. We also discuss the novel
      pathogenesis of specific liposomal component of amphotericin B that contributed
      to the acute cardiopulmonary compromise in our patient leading to subsequent
      myocardial infarction.

PMID- 21734534
TI  - Upper extremity lymphedema index: a simple method for severity evaluation of
      upper extremity lymphedema.
AB  - Measurement of the circumference is the most commonly employed method for
      evaluating extremity lymphedema. However, comparison between different patients
      is difficult with this measurement. To resolve this problem, we have formulated a
      new index, upper extremity lymphedema (UEL) index, which can be easily obtained
      from measurements of the body. We evaluated correlation between UEL index and
      clinical stage in patients with UEL. The UEL indices were significantly
      correlated with clinical stages and could be used as a severity scale. The lower
      extremity lymphedema index makes objective assessment of the severity of
      lymphedema through a numerical rating, regardless of the body type. This
      numerical rating makes the index useful for evaluation of lymphedema severities
      between different cases.

PMID- 21734535
TI  - A reappraisal of the free groin flap in aesthetic craniofacial reconstruction.
AB  - Craniofacial defects are often associated with 3-dimensional volumetric contour
      deficiencies. The free groin flap was historically popular though technical
      limitations subsequently caused its use to fall from favor. We sought to
      determine if a role remained for the free groin flap in aesthetic craniofacial
      reconstruction. From May 2005 to July 2010, 15 patients had 18 consecutive free
      groin flaps performed by the senior surgeon at the R Adams Cowley Shock Trauma
      Center and the Johns Hopkins Medical Institute. Data collected included age, sex,
      operative date, etiology, defect size, recipient vessels, complications, donor
      site closure, and follow-up time. Eighteen groin flaps were used for the patient
      cohort consisting of 10 males and 5 females (mean age, 26 years; range, 18-40
      years) who underwent reconstruction necessitated by various oncologic, traumatic,
      infectious, and congenital etiologies. The average defect size was 7.3 * 6.3 cm
      (range, 3-10 * 1-10 cm). Seventeen flaps were based on the superficial circumflex
      iliac vessels and 1 on the superficial inferior epigastric vessels. Seventeen
      flaps used the superficial temporal artery and vein as the recipient vessels, and
      the remaining flap used the superior thyroid artery and retromandibular vein. Of
      the 18 flaps, 17 survived (94% survival rate). All donor sites were closed
      primarily. Follow-up time ranged from 6 to 60 months. The free groin flap is
      generally underused in the reconstruction of complex craniofacial facial defects.
      Its unique characteristics and minimal donor-site morbidity should prompt the
      reconstructive surgeon to retain the free groin flap in his or her armamentarium.

PMID- 21734536
TI  - A comparison of triamcinolone acetonide and fibrin glue for seroma prevention in
      a rat mastectomy model.
AB  - BACKGROUND: Seroma formation is one of the most common complications after flap
      surgery during the postoperative period. Various methods have been developed to
      overcome this problem, but none of them have been used successfully. Authors used
      topical triamcinolone acetonide to reduce seroma formation in a rat mastectomy
      model and compared its effectiveness with fibrin glue. METHODS: In the rat
      mastectomy model, the authors administered triamcinolone acetonide (experimental
      group I, n=12), fibrin glue (experimental group II, n=12), and saline (control
      group, n=12) beneath the skin flap just before closure of the skin. Seroma
      collections were aspirated and quantified after 7 days, and histologic analysis
      of the skin flaps and chest walls of the rats was performed. RESULTS: The
      experimental group I had a reduced mean seroma volume of 1.79+/-1.32 mL, whereas
      the experimental group II and control group had mean seroma volumes of 4.04+/
      1.43 mL and 8.51+/-2.60 mL, respectively (P<0.05). In semiquantitative analysis
      of inflammation, inflammatory cell count in experimental group I was
      significantly fewer than in the other 2 groups (P<0.001). In addition, seroma
      capsule formation did not occur. CONCLUSIONS: Seroma prevention using
      triamcinolone acetonide is simpler, more economical, and more effective than
      fibrin glue. In proper concentrations, triamcinolone acetonide can be used to
      prevent seroma formation in clinical practice.

PMID- 21734537
TI  - Abdominal contouring procedures increase activity of the coagulation cascade.
AB  - One of the most serious complications in plastic surgery is a thromboembolic
      event. However, little physiologic evidence exists to support the observed
      hypercoagulable state seen in contouring procedures. Twenty-one consecutive
      patients were enrolled prospectively to assess thrombin generation, which
      measures activity of the coagulation cascade, at baseline, intraoperative, and 24
      hours after surgery. Compared with preoperative values, total thrombin generation
      increased by a mean of 997 nM intraoperatively (1.3-fold, P<0.004) and 1406 nM
      postoperatively (1.4-fold, P<0.001) in 9 patients undergoing abdominoplasty
      without deep venous thrombosis (DVT) chemoprophylaxis. The mean thrombin
      generation did not significantly change during or after surgery in 12 patients
      who received heparin for DVT prophylaxis (P=0.3). Thrombin generation was
      significantly less in patients receiving chemoprophylaxis compared with those who
      received no prophylaxis (P<0.01). This suggests abdominal contouring procedures
      induce a significant increase in the activity of the coagulation cascade that can
      be prevented by DVT chemoprophylaxis.

PMID- 21734538
TI  - Risk factors for donor-site seroma formation after immediate breast
      reconstruction with the extended latissimus dorsi flap: a statistical analysis of
      120 consecutive cases.
AB  - The extended latissimus dorsi flap has been widely used for breast
      reconstruction. However, seroma at the donor site is a common complication and
      makes it difficult for reconstructive surgeons to choose it as a primary option.
      We analyzed the association between seroma and reconstructions with extended
      latissimus dorsi flaps. A series of 120 consecutive cases were included in this
      study. The average body mass index (BMI) was 22.1 kg/m, and the mean ratio of the
      flap weight to the extirpated breast weight was equivalent to 101.6%. The mean
      age of patients was 40.3 years. Donor-site seroma was reported in 69.2% (83
      cases) of the total patients. With respect to BMI, flap weight, and age, the
      incidence and duration of donor-site seroma showed statistically significant
      differences (P<0.05). Both the incidence and duration of seroma were
      significantly higher and longer in patients who had high BMI (>23 kg/m), large
      flap (>450 g) for reconstructions, or advanced age (>45 y). In these cases,
      greater attention and additional adjunctive procedures would be needed to prevent
      seroma.

PMID- 21734539
TI  - Prediction of mortality in patients with major burns: clinical and biochemical
      factors.
AB  - OBJECTIVE: The plasma electric charge, in addition to clinical factors, was
      considered to improve the prediction of mortality in patients with major burns.
      METHODS: A software called PICAL 5.0 was used to determinate the plasma electric
      charge in 143 patients with major burns from the intensive care burn unit
      Unfallkrankenhaus Berlin (Germany). In addition, a retrospective study with these
      patients was developed involving: (1) biochemical variables in the first 48
      hours: pH value, [albumin], [Ca(2+)], etc; (2) clinical aspects: age, total body
      surface area and full-thickness surface area burned, diagnosis of inhalation
      injury, etc. A mortality predictive equation was calculated from univariate and
      multivariate logistic regression analyses in a set of randomly chosen
      participants and applied to a validation set of 35 participants. RESULTS: The
      importance of each ion and protein for the equilibrium in the plasma charge is
      determinant. In statistical multivariate analysis, age, total body surface area
      burned, pH value, and [Mg(2+)] were independently associated with mortality.
      CONCLUSIONS: [Na(+)], [HCO(3)(-)] (bicarbonate), and [Cl(-)] are the ions
      contributing the most to the plasma charge equilibrium in patients with major
      burns; a loss of 50% of plasma proteins in the first 48 hours is equivalent to
      the loss of 1 mmol/L of HCO(3)(-). Moreover, the consideration of plasma
      biochemical parameters in the first 48 hours may improve the mortality predictive
      equation of mortality for burned victims.

PMID- 21734540
TI  - The role of full-thickness scalp resection for management of primary scalp
      melanoma.
AB  - BACKGROUND: Scalp melanoma is aggressive and has a proclivity for regional
      metastasis. We hypothesize that subperiosteal scalp melanoma resection reduces in
      transit/satellite recurrence, when compared with subgaleal resection. METHODS: We
      identified patients with intermediate to deep, primary scalp melanoma referred to
      head/neck surgery over an 8-year period. Patients were compared based on scalp
      resection depth, including subperiosteal (resection to the level of calvarium)
      and subgaleal (resection including skin, subcutaneous tissue, and galea). The
      dependent variables were in-transit/satellite recurrence and time to in
      transit/satellite recurrence. RESULTS: Among 48 identified patients, the in
      transit/satellite recurrence rate was 16.7%. Subgaleal resection patients had
      higher in-transit/satellite recurrence rates than subperiosteal resection
      patients (24.0% vs. 8.7%, P=0.155). Among node-negative patients, subgaleal
      resection had significantly higher in-transit/satellite metastasis rates when
      compared with subperiosteal resection (26.3% vs. 0%, P=0.047). CONCLUSION: For
      node-negative, primary scalp melanoma, subperiosteal resection significantly
      decreases in-transit/satellite recurrence when compared with subgaleal resection.
      Given our small sample size, further studies are necessary to confirm these
      results.

PMID- 21734541
TI  - Reconstruction of large meningomyelocele defects with rotation-transposition
      fasciocutaneous flaps.
AB  - Meningomyelocele is one of the most common congenital defects of the central
      nervous system. Reconstruction of these defects must be performed immediately
      after delivery to prevent complications such as primary meningitis and to protect
      the neural tissues. The most important factors in the surgical treatment of
      meningomyelocele defects are the size of the defect, its location, the presence
      of kyphosis, and the quality of the surrounding tissue. The chosen method must be
      a simple one that causes minimal blood loss, requires a short duration of
      surgery, and covers the surface of the neural defect with a soft-tissue mass
      enabling closure without tension. In our study, satisfactory results have been
      obtained using 1 or 2 fasciocutaneous flaps based on the midline in 20 patients
      with large meningomyelocele defects where primary closure was not possible. A
      single flap based superiorly on the midline was sufficient to close the defects
      in patients without kyphosis. In patients with concurrent kyphosis, a second flap
      based inferiorly on the midline has been used. All flaps survived, except for a
      distal partial necrosis observed in 1 patient. In the method we used, we adopted
      a defect reconstruction that is similar to the normal anatomic structures and
      resistant to trauma and infections, and does not sacrifice any muscle tissue.
      According to our clinical experiences, this method is useful for large
      meningomyelocele defects that are unsuitable for primary closure.

PMID- 21734542
TI  - Surgical management of pharyngocutaneous fistula after total laryngectomy.
AB  - PURPOSE: The increased use of radiation in the primary management of laryngeal
      carcinoma has resulted in an increase in pharyngocutaneous fistula (PCF)
      formation after salvage laryngectomy. The impact of this practice on surgical
      management strategies has been analyzed. METHODS: A retrospective review of 177
      patients treated by total laryngectomy for laryngeal or hypopharyngeal squamous
      cell carcinoma was performed. PCF formation was documented and management
      strategies were analyzed. RESULTS: Preoperative radiation therapy (XRT) was
      administered to 86 patients (48.6%). Postoperative PCF developed in 47 patients
      (26.5%), including 30 (34.9%) who had received preoperative XRT versus 17 (18.6%)
      who had not received XRT (P = 0.015). Spontaneous PCF closure occurred in 23
      patients (48.9%). Two patients died with persistent, untreated PCF. Surgical
      closure of PCF was performed in 22 patients (46.8%), including 17 who had
      received preoperative radiation (77.3%). Reconstructive methods included 9 local
      flaps, 17 pectoralis major (PM) flaps, and 2 free jejunal flaps. Seven of the 9
      (77.8%) patients treated with local flaps had received XRT. Three patients had
      successful fistula closure including 2 who had not received radiation. Six of 9
      patients (66.7%) developed recurrent fistulization after local flap closure
      necessitating PM flap closure. Overall, 14 patients (82.4%) had received
      preoperative XRT prior to PM flap closure. Six patients (35.3%) who had received
      XRT developed recurrent fistulization and 5 of these fistulas eventually closed
      with local wound care. The remaining patient succumbed to a carotid artery
      rupture. Two patients required a completion pharyngectomy and free jejunal flap
      reconstruction. PM flaps were used in both cases to provide soft-tissue coverage.
      CONCLUSIONS: Preoperative XRT increases the risk of PCF after laryngectomy and
      the need for surgical closure. Local flap closure has a limited role in the
      surgical management of PCF. PM flap reconstruction has a high complication rate
      including recurrent fistulization in the setting of preoperative radiation.

PMID- 21734543
TI  - Management of massive mastectomy skin flap necrosis following autologous breast
      reconstruction.
AB  - BACKGROUND: The optimal management of severe mastectomy skin flap necrosis
      continues to remain a challenge. Following autologous reconstruction, small or
      minor areas of ischemia/tissue necrosis can result in multiple office visits,
      increased expenses due to dressing supplies and nursing care, and revisional
      operations. The purpose of this study is to describe outcomes of a common
      management strategy for surgeons when confronted with a patient with extensive
      mastectomy skin flap necrosis. METHODS: Between 1997 and 2010, autologous breast
      reconstructions were performed in 805 women and 1076 breasts. Of these, 12
      patients (15 breasts) were identified who met the criteria for massive skin flap
      loss (>30%). Patient photographs and wound measurements were used to estimate
      areas of necrosis. All patients were managed initially with local wound care
      followed by delayed scar excision. RESULTS: Wound closure was ultimately achieved
      in all patients. Of the patients, 40% were active smokers in the perioperative
      period. The average patient age was 49.6 (range, 28-59) years with a body mass
      index of 30.9. The average mastectomy weight was 959.5 g (range, 223-1520). In
      office soft-tissue debridement and local wound care was performed until wound
      closure was complete, which took place at a mean of 120 days (range, 30-300)
      after initial surgery. The average patient had a mean of 10 office visits before
      scar revision. There was an average of 1.7 types of dressing changes needed
      before wound closure. Topical wound therapy included moisturizing gels, wet-to
      dry dressing, and antibiotic ointment. Oral antibiotic therapy was used in 60% of
      patients. Late scar revision was performed in 87% of the patients at an average
      of 8.9 months (range, 1-14) after initial surgery. After the initial flap
      surgery, no patient required skin grafting or hospitalization. CONCLUSIONS: Early
      conservative management followed by late scar revision produced excellent results
      in patients with massive mastectomy skin flap loss. The outcomes described may
      help clinicians and patients in the decision-making process when confronted with
      this difficult problem.

PMID- 21734544
TI  - Compound repair of intraperitoneal onlay mesh associated with the sublay
      technique for giant lower ventral hernia.
AB  - BACKGROUND: Large lower ventral hernias are defined as defects located from 3-cm
      above the symphysis pubis to the umbilicus, and are larger than 10 cm in
      diameter. Surgical repair of these hernias is challenging because of the large
      defect, enormous hernia contents, a narrowed abdominal cavity, and close
      proximity to bony and vascular structures. This study aimed to evaluate a novel
      repair technique with a combination of intraperitoneal onlay mesh and the Rives
      Stoppa technique for these hernias. METHODS: Clinical data of 26 consecutive
      patients with large lower ventral hernias from 2008 to 2010 were reviewed.
      Gradually, the hernia contents were reduced into the abdominal cavity and an
      abdominal binder was applied from 2 weeks preoperatively. At the same time,
      vesical pressure was monitored by instilling normal saline into the bladder
      through a Foley catheter. Compound repair using intraperitoneal onlay mesh
      associated with the Rives-Stoppa technique was undertaken in all these patients.
      RESULTS: Fifteen males and 11 females were included, with a mean age of 55.5+/
      13.2 years and a mean body mass index of 27.8+/-4.5 kg/m. Vesical pressure under
      20 cm H2O was achieved preoperatively. Mean hernia size was 112.5+/-33.5 cm, with
      a mean polypropylene mesh size of 120.4+/-40.2 cm and a mean compound mesh size
      of 220.8+/-76.6 cm. The mean operative time was 155.5+/-38.2 minutes and the
      hospital stay was 12.0+/-3.5 days. Twenty-six patients had a mean follow-up
      period of 14.5+/-6.5 months. One iatrogenic bladder injury occurred because of an
      obscure prevesical space secondary to a previous mesh repair. Four patients had
      seromas, 3 had chronic pain, and 1 had superficial infection, with no
      presentation of abdominal compartment syndrome. No recurrence was observed at
      follow-up. CONCLUSIONS: Compound repair of intraperitoneal onlay mesh associated
      with the Rives-Stoppa technique is a safe and efficient surgical procedure for
      large lower ventral hernia. Both perioperative management and operative
      technology play important roles in management of large lower ventral hernia.

PMID- 21734545
TI  - One-stage immediate breast reconstruction with implants: a new option for
      immediate reconstruction.
AB  - BACKGROUND: The current standard of care for breast implant reconstruction after
      mastectomy is 2-stage reconstruction with placement of tissue expanders followed
      by implants. The immediate use of implants at the time of mastectomy, which
      eliminates the need for a second operative procedure, has been sparsely reported
      and is not yet accepted as the standard of care. This study describes a 1-stage
      immediate implant reconstruction technique and evaluates its risks. METHODS:
      Between 2005 and 2010, immediate implant reconstruction was performed in 43
      sequential patients on a total of 78 breasts. Permanent silicone implants were
      placed at the time of mastectomy with the assistance of acellular dermal matrix
      (ADM). Follow-up was for an average of 575 days. Implant sizes varied widely from
      175 to 800 mL. In order to create the correct breast shape and implant placement,
      specific techniques of acellular dermal matrix placement in the reconstruction
      were critically important. Aesthetic evaluation of the patients was performed,
      evaluating pre- and postoperative photos by 20 evaluators. Pictures were rated
      according to a 4-point Harris breast scale. A 2-sided paired t test was then used
      to compare the rating scores. RESULTS: Complication rates were as follows: seroma
      occurred in 6.4% of breasts; infection resolving with antibiotics occurred in
      2.6%; infection requiring implant removal occurred in 3.8%; and hematoma occurred
      in 1.3%. Neither preoperative breast size nor implant size correlated to an
      increased risk of complications (P>0.05). Complication rate increased with age
      (P=0.02). The average score for the preoperative images was 2.1, whereas the
      postoperative average was 2.4. This represented a statistically significant
      improvement above the baseline (preoperative) breasts with a P<0.001, according
      to a 2-sided paired t test. CONCLUSIONS: With complication rates similar to
      previously reported tissue expander reconstructions, immediate implant
      reconstruction is a viable alternative to 2-stage expander reconstruction,
      presenting many advantages over expander reconstruction while offering the same
      risk profile and eliminating the additional risks, costs, and discomfort of a
      second procedure. Additionally, aesthetic results were highly satisfactory
      according to patients themselves and based on evaluation by independent
      observers.

PMID- 21734546
TI  - The sural compendium: reconstruction of complex soft-tissue defects of leg and
      foot by utilizing the posterior calf tissue.
AB  - The posterior calf tissue can be used both in an antegrade and retrograde manner
      based on the neurovascular axis of the sural nerve, short saphenous vein, and its
      accompanying arteries for reconstruction of the lower limb. We present a simple
      algorithm for reconstruction of knee, leg, ankle, heel, and foot with sural
      flaps. During a period of 9 years (January 2002 to December 2010), reconstruction
      of the lower limb with different varieties of sural flap was performed on 168
      patients. The ages of patients ranged from 4 to 75 years. Of 168 flaps, 154
      survived completely, 9 flaps suffered partial necrosis, while 5 failed
      completely. Delay procedure was used on 67 patients. The sural flap can be
      considered as the workhorse flap and can be used in different ways to deal with
      myriad of clinical situations in which soft-tissue coverage becomes challenging.

PMID- 21734547
TI  - Management of exposure of cardiac pacemaker systems.
AB  - The erosion and exposure of pacemakers are relatively uncommon occurrences but,
      given the number of these devices inserted yearly, they are nevertheless
      occurrences that plastic surgeons are likely to encounter in practice. Although
      there is a general agreement that clinically infected devices are best removed,
      it has been established that exposed but noninfected devices can usually be
      managed conservatively with coverage procedures. Reports in the literature, to
      date, describe a number of different procedures for coverage, and these reports
      generally comprise small numbers of patients. This study describes 16 patients
      referred to a single surgeon over a 14-year period with exposure or suspected
      impending exposure of their cardiac pacemaker systems. Fourteen patients required
      surgical revision for coverage of either the generator or defunctionalized wires.
      Equivalent success was achieved with either subfascial or submuscular coverage in
      11 patients with generators present. Three patients with exposure of
      defunctionalized wires achieved successful coverage with submuscular burial.
      There was no correlation of culture results with recurrence of exposure.

PMID- 21734548
TI  - Versatility of the turn-around technique of the lateral arm flap for hand
      reconstruction.
AB  - The lateral arm flap is a popular flap for hand resurfacing. Despite its many
      advantages, its use is restricted by the available width of the flap. We describe
      the application of this long and narrow flap in a turn-around manner, greatly
      increasing its versatility while achieving primary closure of the donor site. The
      lateral arm flap was designed with extension onto the forearm (extended lateral
      arm flap) and harvested in the usual manner. During inset, the distal segment of
      the flap is brought through a 180 degree "U-turn" to lie adjacent to the proximal
      segment. We analyzed the outcomes of 31 turn-around lateral arm flaps performed
      between 1988 and 2008. All flaps healed well without any vascular compromise.
      Reconstruction of defects with a variety of configurations was performed with a
      maximum flap size of 144 cm. Four patients required split skin grafting to the
      forearm. Primary closure of the lateral arm donor site was achieved in all
      patients. In this article, we demonstrate the ease, reliability, and versatility
      of this simple modification in extending the usefulness of the lateral arm flap
      in hand reconstruction.

PMID- 21734549
TI  - Evolution of the 3-dimensional video system for facial motion analysis: ten
      years' experiences and recent developments.
AB  - Since the implementation of the computer-aided system for assessing facial palsy
      in 1999 by Frey et al (Plast Reconstr Surg. 1999;104:2032-2039), no similar
      system that can make an objective, three-dimensional, quantitative analysis of
      facial movements has been marketed. This system has been in routine use since its
      launch, and it has proven to be reliable, clinically applicable, and
      therapeutically accurate. With the cooperation of international partners, more
      than 200 patients were analyzed. Recent developments in computer vision--mostly
      in the area of generative face models, applying active--appearance models (and
      extensions), optical flow, and video-tracking-have been successfully incorporated
      to automate the prototype system. Further market-ready development and a business
      partner will be needed to enable the production of this system to enhance
      clinical methodology in diagnostic and prognostic accuracy as a personalized
      therapy concept, leading to better results and higher quality of life for
      patients with impaired facial function.

PMID- 21734550
TI  - Soft-tissue optimization of limb salvage with knee endoprosthesis: the 10-year
      experience at the Children's Hospital of Philadelphia.
AB  - PURPOSE: Limb salvage in bone sarcomas requires resection and joint and soft
      tissue reconstruction. Suboptimal coverage can lead to prosthesis infection,
      subsequent hardware exposure, or loss with eventual amputation. In the pediatric
      sarcoma population, it is essential to not only have viable soft-tissue coverage
      but one that minimizes donor site morbidity and maximizes function and growth
      over time. METHODS: This is a retrospective review of all sarcoma patients with
      primary gastrocnemius and soleus muscle flap coverage of modular knee
      endoprosthesis over the 10-year period between 1997 and 2007. All patients had
      resection of the skin at the tibial biopsy site prior to their primary tumor
      resection surgery. After resection of the knee joint and proximal tibia with
      clear margins, the bony defect was reconstructed with an endoprosthesis. The
      gastrocnemius and soleus muscles were then independently rotated to cover the
      prosthesis and the patellar tendon. RESULTS: Eleven patients (10 male, 1 female)
      with an average age of 13 years (range, 10-17) underwent resection of proximal
      tibia. Pathology included osteosarcoma in 9 patients, Ewing in 1, and spindle
      cell sarcoma in 1 patient. All patients had endoprosthetic coverage by
      gastrocnemius and soleus flaps; 4 patients had additional split-thickness skin
      graft over the gastrocnemius. The average level of tibial resection was 16.5 cm
      distal to the articular surface of the proximal tibia. Mean soft-tissue mass
      volume resected with bone was 157 cm. There was one flap failure that was
      reconstructed with a rectus abdominis free flap. Average follow-up was 32 months
      (range, 8-92 months). Two patients succumbed to metastatic disease. In this
      series, there was no limb loss or hardware exposure or infection. All patients
      achieved independent ambulation. Functionally, patients were evaluated based on
      the Musculoskeletal Tumor Society scale. The average score was 29 (out of a
      perfect score of 30). Two patients had transient foot drop that resolved with
      ankle foot orthosis use. Anticipated leg length discrepancy was detected in 3
      patients who underwent opposite limb epiphysiodesis with ultimate limb
      equalization. CONCLUSION: Soft-tissue reconstruction with gastrocnemius and
      soleus muscle flap coverage decreases wound complications and hardware exposure
      while maintaining function in the pediatric population.

PMID- 21734551
TI  - Reconstruction of lower face defect or deformity with submental artery perforator
      flaps.
AB  - BACKGROUND: Reconstruction of lower face defects or deformity often presents as a
      challenge for plastic surgeons. Many methods, including skin graft, tissue
      expander, or free flap are introduced. Submental artery perforator flaps have
      been used in the reconstruction of defects or deformities of the lower face.
      METHODS: Between August 2006 and December 2008, 22 patients with lower face
      defects or deformity underwent reconstruction with pedicled submental artery
      perforator flaps. Their age ranged between 14 and 36 years. The perforator
      arteries were detected and labeled with a hand-held Doppler flowmeter. The size
      of flaps ranged from 4 * 6 to 6 * 7 cm, and the designed flaps included the
      perforator artery. RESULTS: All the flaps survived well, except 1 flap which
      resulted in partial necrosis in distal region and healed after conservative
      therapy. No other complication occurred with satisfactory aesthetic appearance of
      the donor site. CONCLUSIONS: The submental artery perforator flap is a thin and
      reliable flap with robust blood supply. This flap can reduce donor-site morbidity
      significantly and is a good choice for reconstructive surgery of lower face.

PMID- 21734552
TI  - Efficacy of novel collagen/gelatin scaffold with sustained release of basic
      fibroblast growth factor for dermis-like tissue regeneration.
AB  - We have developed collagen/gelatin sponges (CGS) with a gelatin concentration of
      10 wt% to sustain the release of basic fibroblast growth factor (bFGF). The
      objective of this study is to elucidate the efficacy of CGS impregnated with
      different concentrations of bFGF, using mouse skin defects. CGSs impregnated with
      normal saline solution (NSS) or bFGF solution (1, 7, 14, or 50 MUg/cm) were
      implanted into full-thickness skin defects on the backs of mice. The wound area,
      neoepithelium length, and total area of newly formed capillaries in CGS were
      evaluated. The group of CGS with 7-MUg/cm bFGF was significantly superior to the
      NSS group in all evaluated items. CGS impregnated with the appropriate dosage of
      bFGF accelerates dermis-like tissue formation 2 or 3 times earlier than existing
      artificial dermis. The combination of CGS and bFGF could solve the problem of the
      existing artificial dermis and be very promising for the treatment of skin
      defects.

PMID- 21734553
TI  - Hemangioma update: pearls from 30 years of treatment.
AB  - This manuscript is a compilation of clinical lessons learned from 30 years of
      treating hemangiomas. We review relevant clinical anatomy, the role of lasers and
      medications, timing of surgery, and operative judgment, as it pertains to the
      treatment of hemangiomas.

PMID- 21734554
TI  - The spider procedure: a new Z-plasty-based local flap procedure.
AB  - BACKGROUND: Using neighboring similar skin, local flap procedures provide optimal
      aesthetic and functional results in reconstruction of skin defects. Therefore, a
      number of local flap procedures have been described. However, as skin defects
      present limitless variations in size and shape, new flap procedures are still
      needed. Here, we describe a new Z-plasty-based local flap technique, "the spider
      procedure," for closure of the skin defects. METHODS: In this procedure, first,
      the existing defect is surgically converted to a triangle in shape. Then, using a
      modified 5-flap Z-plasty pattern, the flaps are outlined. By transposing the
      elevated flaps in a Z-plasty manner, a tension-free closure is achieved by means
      of tissue relaxation provided by opposing Z-plasties. Over 9 years, this
      technique has been used for closure of various skin defects in 42 patients (19
      men and 23 women) aged 17 to 57 years. This procedure was used for facial defects
      in 20 patients, abdominal defects in 6, upper extremity defects in 7, and lower
      extremity defects in 9 other patients. The defect size ranged between 1.5 and 17
      cm in diameter. RESULTS: A tension-free defect closure was obtained in all
      patients. Except 2 patients with minor flap tip necrosis who underwent secondary
      healing, all patients healed uneventfully and no patient required revision
      surgery in our series. There was no patient with dog-ear formation. A mean follow
      up of 2 years (6 months-9 years) revealed an aesthetically acceptable scar
      formation in all patients. CONCLUSIONS: On the basis of our clinical results, the
      spider procedure seems to be a useful alternative for the closure of various skin
      defects in all regions of the body. Using the advantage of extra tissue
      relaxation provided by opposing Z-plasties, it enables a surgeon to obtain
      tension-free closure of considerably large skin defects without dog-ear
      formation.

PMID- 21734555
TI  - Evaluation of FiberLoop sutures in locking and nonlocking tendon repair.
AB  - The FiberLoop suture has been developed as a double stranded, double-armed suture
      of FiberWire, but has not been previously studied. This is a comparison study of
      FiberLoop, FiberWire, and Ethibond. METHODS: Six groups of bovine tendons were
      randomly sorted for testing. They were cut and repaired using FiberWire,
      FiberLoop, and Ethibond with modified Kessler and modified Krackow repair
      techniques. A 4-0 core suture was used and tested to failure. RESULTS: Both
      FiberLoop and FiberWire were significantly stronger than Ethibond regardless of
      the repair technique used. There was no difference between the nonlocking and
      locking repair technique in any of the suture groups. However, the nonlocking
      technique failed by tissue pull through while the locking technique failed by
      suture breakage. CONCLUSIONS: The FiberLoop suture and the FiberWire suture were
      significantly stronger than the Ethibond suture. Additionally, this study shows
      that the 4-0 suture is of adequate strength to repair a tendon injury. The double
      armed Fiberloop may translate into quicker tendon repairs without sacrificing
      strength.

PMID- 21734556
TI  - Cardiopulmonary bypass techniques and clinical outcomes in Beijing Fuwai
      Hospital: a brief clinical review.
AB  - The purpose of this study is to briefly summarize cardiopulmonary bypass (CPB)
      techniques and clinical outcomes in Beijing Fuwai Hospital. This article
      introduces routine CPB techniques in Fuwai Hospital, including CPB instruments,
      circuit setup, priming, conventional CPB management, myocardial protection, deep
      hypothermic circulatory arrest, ultrafiltration, autologous cell saver blood
      transfusion, and extracorporeal membrane oxygenation (ECMO). Clinical outcomes
      and further improvements of CPB management are also discussed. In 2008, 7,607
      cases of cardiac surgery were performed in Fuwai Hospital, including congenital
      heart disease (48.33%), coronary artery disease (23.30%), rheumatic heart disease
      (19.45%), blood vessel disease (5.90%), reoperative surgery (1.70%), and other
      diseases (1.33%). The use of off-pump coronary artery bypass grafting (CABG) in
      isolated CABG was >50%. Thirty-eight cases of heart transplantation were also
      included. Total operative mortality in 2008 was 1.2%. Average postoperative stay
      was 9.5 days. CPB time was <120 minutes in >70% of the patients, and aortic cross
      clamping time was <60 minutes in >50% of the cases. The self-recovery rate in the
      blood cardioplegia group (69.50%) was lower than the crystalloid cardioplegia
      group (97.40%). Thirty-five patients underwent cardiac surgery, and one patient
      from the cardiac internal medicine wards required ECMO support. Twenty-seven
      patients (75%, mean support time: 123.6 +/- 54.1 hours) were weaned off ECMO
      successfully and discharged without severe complications. In conclusion, clinical
      CPB protocol used in Beijing Fuwai Hospital is a safe, simple, and conventional
      CPB management system that is suitable for practical clinical application in
      China. Further optimization is still needed to improve perfusion quality.

PMID- 21734557
TI  - Timing of heparin and perfusion temperature during procurement of organs with
      extracorporeal support in donors after circulatory determination of death.
AB  - Despite successful resuscitation of donors after circulatory determination of
      death (DCD) with extracorporeal support (ECS), the technique is limited by
      ethical concerns about donor management (heparinization) and the complexity to
      operate the ECS circuit. This work studies different timing of heparin
      administration and the effects of ECS-perfusion temperature. Cardiac arrest (CA)
      was induced in swine. Heparin studies, three groups: 1) PRE5, heparin 5 minutes
      before CA; 2) POST5, heparin 5 minutes after CA, plus 2 minutes external chest
      compressions; and 3) POST30, heparin with the initiation of ECS after 30 minutes
      CA. Perfusion temperature study, two groups: 1) normothermic, ECS-38.5 degrees C
      after 30 minutes CA and 2) room temperature, ECS-25.5 degrees C for the first 90
      minutes, followed by ECS-38.5 degrees C. Heparin studies: ECS target flows (>50
      ml/kg/min) were not achieved in the POST30 group, affecting local organ perfusion
      as observed with poor bile (<4 ml/min) and urine output (<25 ml/min), when
      compared with the other groups (normal values). Temperature study: In both
      groups, ECS target flows were reached, and urine/bile output was restored.
      Heparinization 5 minutes after CA is equivalent to premortem heparinization in
      this ECS-DCD model. Heparinization after CA could reduce ethical concerns. Donors
      after circulatory determination of death were successfully resuscitated at both
      temperatures, suggesting that the heat exchanger/water heater can be removed to
      simplify the ECS circuit.

PMID- 21734558
TI  - A method of comparison of different regimens for dialyzing single-pool solutes.
AB  - Many points of reference have been used to compare and rationalize extracorporeal
      end-stage renal disease therapy. We address a specific part of the subject: the
      effect of the delivery schedule on a predetermined dose of dialysis, e.g., weekly
      Kt/V. Steady (time-invariant) application of dialysis absolutely minimizes time
      averaged and peak concentrations of any extractable solute. However, such dosing
      is often impractical; we assess the effectiveness of achievable slow regimens
      relative to steady dosing, using the single-pool approximation, applicable to
      slow regimens. Dose scheduling has been previously considered. We combine and
      discuss prior observations and establish continuous dosing as an easily
      quantifiable reference point, and we emphasize fundamental patterns common to
      different schedules. Thus, we enable rapid comparison of the many "slow" dialysis
      regimens presently under consideration using two intuitive parameters to
      encompass dialysis dosing: intermittency and intensity. These parameters define
      any repetitive dialysis pattern. A method for evaluating any combination of them
      is given with formulae, graphically, and with examples. Intermittency increases
      average solute concentration only slightly, but the frequency and spacing of
      intermittent treatments strongly affect peak solute concentrations. With steadier
      solute removal, cycling of solvent (water) stores is likely to remain the
      dominant source of disequilibrium in patients.

PMID- 21734559
TI  - A blood assist index control by intraaorta pump: a control strategy for
      ventricular recovery.
AB  - Left ventricular assist devices (LVAD) are increasingly used for long-term
      support in heart failure patients. To promote ventricular reverse remodeling, a
      defined and adjustable energy distribution of LVAD and native heart is important.
      Therefore, a blood assist index (BAI), which is a ratio of power of LVAD and
      total power of the cardiovascular system, is defined to indicate the energy
      distribution of LVAD and native heart. Subsequently, an LVAD control algorithm
      that uses the BAI as control input is designed. The control strategy maintains
      the measured BAI tracking the desired BAI. A mathematic model of cardiovascular
      system is used to verify the feasibility of control strategy in the presence of
      left ventricular failure, physical active, and a recovery of cardiac function.
      The simulation results show that the control strategy automatically increases
      pump speed in response to the reduced peripheral systemic resistance (5,500 vs.
      6,000 RPM). When Emax is increased from 0.6 to 1.8 mm Hg/ml to mimic left
      ventricular recovery, the blood flow is automatically increased from 5 to 8
      L/min. As a key feature, the proposed control strategy provides a defined and
      adjustable energy distribution of LVAD and native heart by regulating the
      rotational speed of the pump, which is benefit to promote the left ventricular
      reverse remodeling.

PMID- 21734560
TI  - Flow field study comparing design iterations of a 50 cc left ventricular assist
      device.
AB  - The Randomized Evaluation of Mechanical Assistance for the Treatment of
      Congestive Heart Failure (REMATCH) study shows that implanted ventricular assist
      devices improve survival time and quality of life when used as a permanent
      therapy in patients who do not qualify for heart transplant. The success of the
      pulsatile 70 cc stroke volume left ventricular assist device (LVAD) developed by
      Penn State has led to the development of a 50 cc stroke volume pump for use in
      patients with smaller chest cavities to benefit a larger patient population. The
      initial 50 cc pump shows regions of in vivo thrombus formation, which correlate
      to low wall shear rates within the device. In an in vitro evaluation of three new
      designs (V-2, V-3, and V-4) of the 50 cc LVAD, identical except for the location
      and orientation of their outlet ports, particle image velocimetry (PIV) is used
      to capture planar flow field data within the pumps. V-2 has an outlet port that
      is located parallel to the inlet. In V-3, the outlet port is rotated away from
      the inlet port, with the intention of minimizing the amount of fluid turning
      needed to exit the device. With V-4 the outlet port is moved to the center of the
      pump to prolong the desirable rotational flow. PIV data were taken at six planar
      locations within the pump. Although the modifications to the outlet port
      locations serve their intended purpose, they also introduce unwanted changes in
      the flow. Poorer wall washing and weaker rotational flow are observed with V-3
      and V-4. Although the differences between the devices are subtle, the device that
      has the most desirable flow characteristics is V-2.

PMID- 21734561
TI  - Small duplication of chromosome (7)(p22.1p22.2) and consideration of a dup 7p
      syndrome critical region.

PMID- 21734562
TI  - Alpha-2-agonists in day case anaesthesia.
AB  - PURPOSE OF REVIEW: Alpha-2-agonists have long been known to have anaesthetic
      sparing, sedative and analgesic properties which are desirable in day case
      anaesthesia. Their routine use was hampered by a high incidence of undesirable
      effects, however. In recent years, there have been many attempts to define a role
      for these unique agents in which their benefits would outweigh their apparent
      disadvantages. RECENT FINDINGS: Many recent studies have confirmed the usefulness
      of alpha-2-agonists in providing sedation and analgesia, although the results
      have been far from consistent. Some, but by no means all studies have shown
      advantages over alternative agents, but concerns also remain over acute and
      possible long-term adverse effects. SUMMARY: Alpha-2-agonists still have no
      clearly defined routine role in day surgery. Their most promising application is
      in limiting recovery agitation in children, but even here, there remain concerns
      about their routine use.

PMID- 21734563
TI  - Induction of innate immunity in control of mucosal transmission of HIV.
AB  - PURPOSE OF REVIEW: To present evidence of the role of innate mucosal immunity and
      to harness this arm of immunity in protection against HIV infection. RECENT
      FINDINGS: Dendritic cells, monocytes, natural killer (NK) cells and gammadelta T
      cells are critical in innate immunity, which is mediated by Toll-like receptor
      (TLR) and recently identified stress pathways. Complement factors, cytokines and
      chemokines have diverse functions usually affecting HIV infection indirectly. A
      novel group of innate intracellular HIV restriction factors has been identified -
      APOBEC3G, TRIM5alpha and tetherin - all of which are upregulated by type I
      interferons and some by vaccination and TLR agonists. Whereas innate immunity
      conventionally lacks memory, recent evidence suggests that some of the cells and
      intracellular factors may express immunological memory-like features. SUMMARY:
      Innate mucosal immunity may provide early effective control of HIV transmission
      and replication. Some vaccines can enhance innate immune factors, such as
      APOBEC3G and control HIV during the eclipse period, allowing full weight of
      neutralizing and/or cytotoxic T cells to develop and prevent mucosal HIV
      infection. The next generation of vaccines should be designed to target both
      innate and adaptive immune memory responses.

PMID- 21734564
TI  - Macrophages and HIV-1.
AB  - PURPOSE OF REVIEW: Macrophages play an important role in HIV-1 pathogenesis and
      contribute to the establishment of the viral reservoir responsible for continuous
      virus production. This review will discuss new insights into HIV-1 infection in
      macrophages and the effect of infection on immune function and pathology. RECENT
      FINDINGS: New cellular factors interacting with various steps of the HIV-1
      replication cycle, such as entry, integration, transcription, and assembly of new
      viral progeny, have been identified. Cellular and viral microRNAs have been shown
      to regulate virus replication, promote viral latency, and prolong cell survival.
      Interference with innate immune functions, like phagocytosis, autophagy, cytokine
      production, and T-cell activation by HIV-1 has been found to contribute to virus
      replication and latency. Growing evidence indicates an important role of infected
      macrophages in a variety of HIV-1-associated diseases, including neurocognitive
      disorders. SUMMARY: Under combined antiretroviral therapy (cART), HIV-1 continues
      to persist in macrophages. Better understanding of HIV-1 infection in macrophages
      may lead to new adjunctive therapies to improve cART, specifically targeting the
      viral reservoir and ameliorating tissue-specific diseases.

PMID- 21734565
TI  - Host genetic polymorphisms associated with innate immune factors and HIV-1.
AB  - PURPOSE OF REVIEW: Our understanding of the early events in HIV-1 infection
      continues to grow, along with the heightened recognition of the important
      contribution that innate immunity plays in response to HIV-1. Here, we review the
      epidemiological and functional studies of genetic polymorphisms associated with
      innate immune factors that are believed to modulate host responses, focusing
      specifically on recent findings related to Toll-like receptor, cytokine, host
      restriction and KIR genes and their activities. RECENT FINDINGS: A growing number
      of genomic studies have described polymorphisms in innate immune genes that are
      associated with early postseroconversion events, including TLR4, TLR9, IRF-3,
      TRIM5alpha and the ABOBEC3 gene family. Genetic and functional data confirm the
      importance of KIR-HLA interactions and provide new understanding of the role of
      innate restriction factors in resistance to HIV-1 and disease progression.
      SUMMARY: Single-gene, genome-wide association and expression studies have
      permitted the identification of innate immune genes and their variants that
      contribute to protection from disease progression. Characterization of the
      pathogen-innate immune system interactions and discovery of new and rare host
      genetic variants that account for a portion of the observed variance in the HIV-1
      phenotype is critical to gain new insights into promising treatment and
      prevention strategies.

PMID- 21734566
TI  - Targeting HIV-1 innate immune responses therapeutically.
AB  - PURPOSE OF REVIEW: The early stage of HIV-1 infection is when the virus is most
      vulnerable, and should therefore offer the best opportunity for therapeutic
      interventions. This review addresses the recent progress in the understanding of
      innate immune responses against HIV-1 with focus on the potential targets for
      prevention of viral acquisition, replication and dissemination. RECENT FINDINGS:
      Research indicates that the host-derived factor trappin-2/elafin is protective
      against HIV, whereas semen-derived enhancer of viral infection and defensins 5
      and 6 enhance viral transmission. Further, studies suggest that stimulation of
      TLR4 and inhibition of TLR7-9 pathways may be HIV suppressive. The regulation and
      function of viral restriction factors tetherin and APOBEC3G have been
      investigated and a molecule mimicking the premature uncoating achieved by
      TRIM5alpha, PF74, has been identified. Chloroquine has been shown to inhibit
      plasmacytoid dendritic cell activation and suppress negative modulators of T-cell
      responses. Blockade of HMBG1 has been found to restore natural-killer-cell
      mediated killing of infected dendritic cells, normally suppressed by HIV-1.
      Interestingly, when used as adjuvants, EAT-2 and heat shock protein gp96
      reportedly enhance innate immune responses. SUMMARY: Several targets for innate
      immunity-mediated therapeutics have been identified. Nonetheless, more research
      is required to unveil their underlying mechanisms and interactions before testing
      these molecules in clinical trials.

PMID- 21734567
TI  - Innate immunity in acute HIV-1 infection.
AB  - PURPOSE OF REVIEW: Acute HIV-1 infection (AHI) is composed of the eclipse phase,
      during which the transmitted virus struggles to avoid eradication and achieve
      amplification/spread; the expansion phase when virus disseminates and undergoes
      exponential replication associated with extensive CD4+ T-cell destruction; and
      the containment phase when set-point levels of viremia and immune activation are
      established. The importance of interactions between HIV-1 and innate responses in
      determining events throughout AHI is increasingly recognized, and is reviewed
      here. RECENT FINDINGS: During the eclipse phase, HIV-1 subverts dendritic cell
      functions to promote its replication at mucosal sites and employs multiple
      strategies to minimize control by type 1 interferons. Systemic virus
      dissemination is associated with widespread activation of innate responses which
      fuels HIV-1 replication. To minimize the protective effects of innate responses,
      HIV-1 resists control by natural killer cells and may impair innate regulation of
      adaptive responses. Innate responses remain chronically activated after HIV-1
      containment which is thought to drive HIV-1 pathogenesis. SUMMARY: Innate
      responses are pivotal determinants of events at all stages of AHI. Increased
      understanding of mechanisms involved in innate control of HIV-1 and pathways
      regulating innate activation during HIV-1 infection could facilitate development
      of novel approaches to combating this infection.

PMID- 21734568
TI  - HIV-1 infection and induction of interferon alpha in plasmacytoid dendritic
      cells.
AB  - PURPOSE OF REVIEW: Loss of blood plasmacytoid dendritic cell (pDC) in HIV-1
      infection is thought to impact on adaptive immune responses whilst the virus also
      induces aberrant interferon alpha (IFN-alpha) production that may fuel chronic
      immune activation and drive disease progression. Recent attention has focussed on
      the pathway of HIV-induced IFN-alpha production by pDC and the new data are
      reviewed here together with the pathway leading to infection. RECENT FINDINGS:
      Attachment to CD4 and chemokine co-receptors is essential for HIV-1 infection.
      Although CD4, but not co-receptor binding, is a major route for passage to
      endosomes and triggering of IFN-alpha secretion this may also occur by CD4
      independent mechanisms involving other receptors. In contrast to other Toll-like
      receptor (TLR)-7 ligands and RNA viruses that stimulate pDC to secrete IFN-alpha
      for 2-3  h, HIV-1-stimulated pDC can give sustained IFN-alpha production for up
      to 48  h which may contribute to chronic immune activation. This may reflect
      retention of HIV in early endosomes which also seems to be associated with
      incomplete maturation induced by HIV. SUMMARY: HIV-1-pDC interactions contribute
      to pathogenesis through depletion and aberrant IFN-alpha production. New data on
      the pathway of pDC HIV-stimulated IFN-alpha secretion may facilitate therapy to
      reduce chronic immune activation and slow disease progression.

PMID- 21734569
TI  - Interactions of diarrhea, pneumonia, and malnutrition in childhood: recent
      evidence from developing countries.
AB  - PURPOSE OF REVIEW: This review highlights recent progress toward understanding
      complex interactions between diarrhea, pneumonia, and undernutrition among
      children in low-income and middle-income countries. RECENT FINDINGS: New studies
      parallel earlier reports that diarrhea and pneumonia impair children's growth and
      that underlying malnutrition is a major risk factor for these conditions.
      Episodes of diarrhea may predispose to pneumonia in undernourished children.
      Additional studies support breastfeeding and micronutrient supplementation for
      the prevention and control of diarrhea and pneumonia. Malnutrition may partially
      account for the reduced efficacy of oral rotavirus vaccines in low-income
      countries. Immunization of pregnant women against influenza also appears to
      reduce intrauterine growth retardation. Immunization of infants against
      Streptococcus pneumoniae may improve their growth. New genetic studies indicate
      that polymorphisms in apolipoprotein E or the leptin receptor modulate children's
      risk for diarrhea and Entamoeba histolytica infection, respectively, thereby
      linking two genes important for lipid metabolism to enteric infections. SUMMARY:
      Significant advances have been made in understanding the vicious cycle of
      malnutrition, diarrhea, and pneumonia in developing countries. Future challenges
      will be to translate this progress into effective and widely accessible public
      health measures.

PMID- 21734570
TI  - Schistosomiasis: from drug deployment to drug development.
AB  - PURPOSE OF REVIEW: Schistosomiasis is a chronic and morbid disease that affects
      hundreds of millions of the poorest individuals in (sub)tropical regions,
      particularly sub-Saharan Africa. Just one drug, praziquantel (PZQ), is available.
      As discussed, efforts to expand mass drug administration programs may accelerate
      the emergence of resistance. In addition, PZQ's peculiar pharmacological profile
      and undefined mechanism of action(s) complicate discriminating incomplete
      efficacy from true resistance. Accordingly, and in spite of the challenges
      associated with developing new antischistosomals as discussed herein,
      alternatives to PZQ should be identified. Various strategies to do this are
      highlighted here. RECENT FINDINGS: The last 2 years have witnessed more
      engagement of the necessary infrastructure combined with the application of the
      latest strategies and technologies to facilitate antischistosomal drug discovery.
      Preclinical and clinical evaluation of new chemistries has benefited from various
      consortia and institutions that underwrite drug development for antiparasitics in
      general. Drug repositioning, target-based drug design, improved automation for
      compound screening, genomics and functional genomics are just some of the tools
      now being applied to identify possible new drugs and drug targets. SUMMARY: The
      new momentum toward the discovery of alternatives to PZQ is encouraging but needs
      to be sustained by a stronger advocacy for drug development, in addition to drug
      deployment.

PMID- 21734571
TI  - Neural regulation of cholesterol metabolism.
AB  - PURPOSE OF REVIEW: The increasing incidence of obesity and diabetes worldwide are
      critical risk factors for the development of cardiovascular disease. Although the
      role of the central nervous system (CNS) in the control of fat mass and glucose
      metabolism has been studied in detail, less is known about the contribution of
      neural-derived signals in the development of systemic dyslipidemia. In this
      review we summarize and analyze evidence suggesting a specific role of the CNS in
      the control of systemic cholesterol metabolism and circulating plasma lipids
      levels. RECENT FINDINGS: Although early reports based in lesions or electrical
      stimulation suggested a role for CNS-derived signals in the development of
      dyslipidemia, more recent findings have confirmed the involvement of specific
      neural pathways critical for the neuroendocrine control of cholesterol metabolism
      and plasma lipid levels. SUMMARY: The identification of the pathways targeted by
      the CNS to control plasma lipid levels could offer alternative targets to create
      efficient novel therapies for the treatment of several metabolic syndrome
      components including dyslipidemia.

PMID- 21734572
TI  - Susceptibility of LDL and its subfractions to glycation.
AB  - PURPOSE OF REVIEW: To highlight the potential importance of glycation as an
      atherogenic modification of LDL, factors determining glycated apolipoprotein B in
      vivo and susceptibility of LDL to glycation in vitro. We also discuss the
      distribution of glycated apolipoprotein B across different LDL subfractions in
      healthy controls, patients with type 2 diabetes and metabolic syndrome. RECENT
      FINDINGS: Small, dense LDL, which is known to be most closely associated with
      atherogenesis, is more preferentially glycated in vivo and more susceptible to
      glycation in vitro than more buoyant LDL. Glycation and oxidation of LDL appear
      to be intimately linked. In patients with type 2 diabetes, plasma glycated
      apolipoprotein B correlated with small, dense LDL apolipoprotein B, but not with
      HbA1c. Glycated apolipoprotein B is significantly lower in statin-treated type 2
      diabetes compared with those not on statins. SUMMARY: Glycation of LDL occurs
      chiefly because of the nonenzymatic reaction of glucose and its metabolites with
      the free amino groups of lysine of which apolipoprotein B is rich. Higher
      concentrations of glycated LDL are present in diabetes than in nondiabetic
      individuals and metabolic syndrome. Even in nondiabetic individuals, however,
      there is generally more circulating glycated LDL than oxidatively modified LDL.
      Probably, oxidation and glycation of LDL are partially interdependent and
      indisputably coexist, and both prevent LDL receptor-mediated uptake and promote
      macrophage scavenger receptor-mediated LDL uptake. The recognition that LDL
      glycation is at least as important as oxidation in atherogenesis may lead to
      improvements in our understanding of its mechanism and how to prevent it.

PMID- 21734573
TI  - Serum amyloid A in atherosclerosis.
AB  - PURPOSE OF REVIEW: Serum amyloid A (SAA) is a family of acute-phase proteins
      which are shown to correlate with cardiovascular disease, but whether this SAA
      contributes causally to atherosclerosis development or reflects underlying
      disease or risk factors remains unclear. RECENT FINDINGS: SAA has been detected
      within atherosclerotic lesions and within adipose tissue where it is hypothesized
      that it may play a contributory role in disease development. In the acute-phase
      response SAA is synthesized by the liver and transported primarily in association
      with HDL. However, there is a growing literature suggesting that localized
      synthesis of SAA within the vasculature, or adipose tissue, may play a distinct
      role in disease development. Furthermore, SAA can be found in association with
      apoB-containing lipoproteins, in which its biological activity may be different.
      SUMMARY: This review will discuss recent experimental evidence supporting a
      causal role of SAA with atherosclerosis.

PMID- 21734574
TI  - Facioscapulohumeral muscular dystrophy: molecular pathological advances and
      future directions.
AB  - PURPOSE OF REVIEW: Recent advances have provided a model for understanding the
      underlying molecular genetic changes in facioscapulohumeral muscular dystrophy
      (FSHD). This review will highlight our current understanding and future research
      directions. RECENT FINDINGS: FSHD typically results from contraction of a
      critical number of D4Z4 repeats in a macrosatellite repeat array on chromosome
      4q35. Contraction leads to loss of DNA methylation and heterochromatin markers in
      the 4q35 D4Z4 region, resulting in relaxation of the chromatin structure and
      release of DUX4 repression. DUX4, a retrogene contained in the D4Z4 repeats, is
      normally epigenetically silenced in somatic cells. Stable expression of DUX4,
      however, can only occur in the presence of a permissive genetic background, which
      contains a polyadenylation signal sequence that stabilizes DUX4 mRNA. Expression
      of DUX4 mRNA and protein occurs at low frequency but in high abundance in FSHD
      myotube nuclei. DUX4 expression in transfection studies induces apoptosis and
      interferes with myogenesis. SUMMARY: FSHD results from a unique combination of
      genetic and epigenetic changes on 4q35 leading to release of repression of DUX4,
      causing disease in a toxic gain-of-function manner. Questions remain regarding
      the normal function of DUX4 and how expression of DUX4 in somatic cells leads to
      FSHD.

PMID- 21734575
TI  - Extracting functional networks with spatial independent component analysis: the
      role of dimensionality, reliability and aggregation scheme.
AB  - PURPOSE OF REVIEW: Clinical studies have differentiated functional brain networks
      in neurological patient and control populations using independent component
      analysis (ICA) applied to functional MRI (fMRI). Principal component analysis
      (PCA) is used to reduce the data dimensionality to make this feasible. The role
      of this choice is reviewed in connection with the accuracy and the reliability of
      the ICA results and the schemes of data aggregation in population studies. RECENT
      FINDINGS: It has been pointed out recently that it is important to critically
      explore the ICA model orders without relying on strictly predetermined PCA
      cutoffs for the number of components. We further illustrate this aspect
      empirically by showing that a large enough range of dimensions may exist where
      ICA components remain accurate but also that the minimum PCA dimension required
      to reliably extract the best ICA maps may vary substantially across subjects.
      Moreover, with the aid of a simple simulation, we show that reliable independent
      components can still be recovered beyond a theoretical PCA cutoff. SUMMARY: The
      role of the PCA cutoff and its impact on the accuracy and reliability of the ICA
      results should be carefully considered in future clinical fMRI studies.

PMID- 21734577
TI  - Hereditary ovarian cancer: recent molecular insights and their impact on
      screening strategies.
AB  - PURPOSE OF REVIEW: This review will focus on the implications of BRCA status in
      the patient with high-grade serous ovarian cancer, the differences between BRCA1
      and BRCA2 mutations, and the most effective risk-reducing strategies. RECENT
      FINDINGS: Women with BRCA-associated epithelial ovarian cancer represent a unique
      group who commonly are diagnosed at a younger age, have advanced high-grade
      serous disease, have improved sensitivity to platinum-based chemotherapy in both
      the upfront and recurrent setting, and have an overall improved prognosis.
      Promising novel therapeutic agents such as poly (ADP-ribose) polymerase
      inhibitors have increased activity in patients with inherited BRCA mutations and
      may also have a role in patients with noninherited tumors that have decreased
      BRCA activity. Risk-reducing salpingo-oophorectomy (RRSO) is effective in
      decreasing risks of both breast and gynecologic cancer in women with BRCA
      mutations. However, when counseling women at inherited risk, the inherent
      phenotypical differences between BRCA1 and BRCA2 mutations must be considered.
      SUMMARY: Patients with BRCA-associated epithelial ovarian cancer have improved
      response to platinum-based chemotherapy, improved survival, and may be
      appropriate candidates for treatment with novel targeted therapies. RRSO remains
      the most effective risk-reduction strategy in women with BRCA mutations.

PMID- 21734576
TI  - Novel frontiers in ultra-structural and molecular MRI of the brain.
AB  - PURPOSE OF REVIEW: Recent developments in the MRI of the brain continue to expand
      its use in basic and clinical neuroscience. This review highlights some areas of
      recent progress. RECENT FINDINGS: Higher magnetic field strengths and improved
      signal detectors have allowed improved visualization of the various properties of
      the brain, facilitating the anatomical definition of function-specific areas and
      their connections. For example, by sensitizing the MRI signal to the magnetic
      susceptibility of tissue, it is starting to become possible to reveal the laminar
      structure of the cortex and identify millimeter-scale fiber bundles. Using
      exogenous contrast agents, and innovative ways to manipulate contrast, it is
      becoming possible to highlight specific fiber tracts and cell populations. These
      techniques are bringing us closer to understanding the evolutionary blueprint of
      the brain, improving the detection and characterization of disease, and help to
      guide treatment. SUMMARY: Recent MRI techniques are leading to more detailed and
      more specific contrast in the study of the brain.

PMID- 21734578
TI  - Merkel cell polyomavirus infection and Merkel cell carcinoma in HIV-positive
      individuals.
AB  - PURPOSE OF REVIEW: Merkel cell polyomavirus (MCPyV) was recently discovered in
      Merkel cell carcinoma (MCC), an aggressive nonmelanoma skin tumour. MCC incidence
      has been rising in the last decades. Immunocompromised individuals such as HIV
      infected patients have an increased risk for MCC development. RECENT FINDINGS:
      MCPyV is found--mostly integrated into the host genome--in approximately 80% of
      MCC. The causal role of MCPyV in MCC development has been corroborated by several
      recent studies. Cutaneous MCPyV infection is acquired early in life and is
      widespread in the general population. In HIV-positive patients, MCPyV-DNA has
      been detected on the skin, on oral and anogenital mucosa, and in plucked eyebrow
      hairs. Compared with healthy controls, MCPyV prevalence is increased in HIV
      infected individuals and severe HIV-related immunosuppression is associated with
      elevated cutaneous MCPyV-DNA loads. This could explain the increased MCC risk
      found in HIV-infected individuals. MCC in HIV-infected patients occurs at a
      relatively young age and frequently on sites not exposed to sunlight. SUMMARY:
      Guidelines for screening and early detection of MCC should be developed for HIV
      positive patients. Future studies should evaluate changes in MCC incidence rates
      in HIV-infected individuals and analyse the effect of immune restoration by
      (early) antiretroviral therapy on MCC incidence and on cutaneous MCPyV load.

PMID- 21734579
TI  - Cervical cancer treatment in Africa.
AB  - PURPOSE OF REVIEW: This review is to inform the reader about the current
      situation with regard to treatment of cervical cancer in Africa and the barriers
      and complexities faced in most African countries. It also reviews the natural
      history of cervical cancer, the new 2009 International Federation of Gynecology
      and Obstetrics staging, and current treatment guidelines for cervical cancer.
      RECENT FINDINGS: There have been no dramatic new findings in the treatment of
      cervical cancer other than newer approaches to fertility-sparing surgery and the
      addition of concomitant chemotherapy to radiation for advanced cervical cancer
      and the data from randomized trials that have shown an improved overall and
      disease-free survival. The most important new findings in cervical cancer pertain
      to cervical cancer prevention strategies, which included using alternative
      approaches to cytology and the introduction of human papillomavirus (HPV)
      vaccination. SUMMARY: Cervical cancer is the commonest cancer cause of death
      among women in developing countries and efforts to prevent the disease using
      newer approaches and HPV vaccination should be implemented. Detection of cervical
      cancer at an early stage is associated with excellent survival but most women in
      developing countries present with advanced and often untreatable disease. The
      ratio between incidence and mortality from cervical cancer remains very high,
      largely due to lack of access to appropriate anticancer therapies in African
      countries.

PMID- 21734580
TI  - Maintenance therapy in follicular lymphoma.
AB  - PURPOSE OF REVIEW: This article reviews the potential benefit of maintenance
      therapy for patients with follicular lymphoma. RECENT FINDINGS: Follicular
      lymphoma, despite substantial improvements in survival, is usually incurable.
      Several randomized studies have shown that the combination of anti-CD20 and
      chemotherapy can improve overall survival for these patients. Recently, the old
      concept of maintenance treatment developed for acute leukemias was reintroduced
      in the treatment of indolent lymphomas. On the basis of its favorable toxicity
      profile, single agent rituximab remains a valuable option when given in a
      prolonged schedule to obtain durable remissions. SUMMARY: A first remission is
      easily obtained but relapses appear unavoidable. Patients achieving a partial
      response have poorer outcomes compared with those achieving complete remission.
      Furthermore, it has been demonstrated that among patients with follicular
      lymphoma who reach complete remission, those obtaining negative minimal residual
      disease, as assessed by molecular biology, have a better outcome compared with
      those remaining with residual disease. There is, therefore, a rationale to give
      additional treatment in an attempt to eradicate or to control the lymphoma cells
      responsible for relapse. An ideal maintenance regimen would have limited toxicity
      and should be easy to administer. Results of the International Primary Rituximab
      and Maintenance study show that 2 years of rituximab maintenance prolongs
      progression free survival, delays the time to next antilymphoma treatment and
      improves the quality of response in patients with previously untreated follicular
      lymphoma. Rituximab maintenance was well tolerated with a limited number of
      adverse events.

PMID- 21734581
TI  - Radiation for bone metastases.
AB  - PURPOSE OF REVIEW: To synopsize the current state-of-the-art for radiation and
      treatment of painful bone metastases with a focus on prostate cancer. RECENT
      FINDINGS: Although external beam radiation has long been known to palliate
      painful bone metastatic disease for patients with prostate cancer, new studies
      continue to evolve in this area. Data from randomized studies over the past
      decade emphasize that palliation can be achieved with single-fraction radiation
      strategies. Despite these data, and various supportive national and international
      guidelines, single-fraction regimens are relatively underutilized in the USA as
      compared with other countries. In addition to external beam radiation, beta
      emitting isotopes are also effective as systemic agents for the palliation of
      painful bone metastases. New alpha-emitters such as Alpharadin (radium-223) are
      under current development but remain unproven at this time and recent data
      indicate that this agent can prolong survival in patients with advanced prostate
      cancer. SUMMARY: Radiation in various forms is highly effective for palliation of
      pain associated with bone metastases.

PMID- 21734582
TI  - Role of vertebral augmentation procedures in the management of vertebral
      compression fractures in cancer patients.
AB  - PURPOSE OF REVIEW: To review the current status of vertebral augmentation
      procedures (VAPs) in the management of symptomatic vertebral compression
      fractures (VCFs) in cancer patients. RECENT FINDINGS: The natural history of VCFs
      in the cancer setting is presumably different from the one seen with osteoporotic
      fractures. Factors contributing to the poor outcome with conservative treatment
      in cancer patients include continued bone loss due to tumor invasion, poor
      nutritional status, immobilization, prolonged steroid use, gonadal ablation,
      chemotherapy and radiotherapy. VAPs have been shown by retrospective and
      prospective randomized studies to be effective in treating symptomatic VCFs.
      Advantages of VAPs include immediate pain relief, avoiding delays in
      chemoradiation, outpatient care in the majority of cases, biopsy, vertebral
      height restoration, and potential antitumor effect of bone cement. Results from
      the prospective randomized Cancer Fracture Evaluation (CAFE) trial show
      superiority of balloon kyphoplasty (BKP) over conservative management in cancer
      patients with VCFs with similar rate of adverse events between treatment arms.
      Additionally, the field is still evolving with advances such as combination with
      radiosurgery and spinal radiofrequency ablation (RFA), use of kyphoplasty without
      a balloon and highly viscous cement to prevent leakage. SUMMARY: VAPs are well
      tolerated and effective methods to provide palliative care for cancer patients
      with VCFs and should be offered to symptomatic patients.

PMID- 21734583
TI  - Palliative sedation: ethical perspectives from Latin America in comparison with
      European recommendations.
AB  - PURPOSE OF REVIEW: Palliative sedation is a standard procedure used in palliative
      care especially for patients at the very end of their lives, who are enduring
      otherwise intractable suffering. It consists of the administration of sedatives
      and, when necessary, other drugs, usually by infusion, either subcutaneously or
      intravenously, at the necessary rate to achieve the patient's relief, by means of
      reducing the consciousness of the patient. If this administration is not
      discontinued, the usual outcome is the patient's death. So, the most frequent
      criticisms regarding the procedure are those that consider it as a form of
      euthanasia. The intention of the review is analyzing the status questionis in
      Europe and Latin America. RECENT FINDINGS: Current thinking and research about
      this issue refers especially to the terminology, the boundaries between
      palliative sedation and slow euthanasia, especially in pediatric settings, the
      lacking of precise definition for concepts such as refractory symptoms and
      unbearable suffering, and the place for existential suffering in this context;
      the ethical positioning of Latin-American normative and authors is similar to
      that of Europe. SUMMARY: It does not seem that solution to the conflicting points
      will come from better guidelines or more experts' meetings. Instead, efforts
      should be directed to reinforce moral, professional integrity, within the
      framework of an ethics of virtue, as inherent to palliative care. Such ethics can
      effectively be taught and infused, and then required to all healthcare
      professionals.

PMID- 21734584
TI  - End of life care sedation for children.
AB  - PURPOSE OF REVIEW: This article is aimed to review updated research on end-of
      life care sedation (EOLC-S) for children and aspects surrounding this issue.
      RECENT FINDINGS: Prevalence of EOLC-S for children may vary across countries on
      account of cultural differences, in terms of settings, legal issues and
      perceptions about EOLC-S, which lead to variation in patient selection and
      management. Although home is the preferred place of death for families, research
      shows hospital settings and ICUs to be the most frequent places where children
      die. Data on how to define refractory symptoms and update research on drug
      selection and dosing are lacking. Nature of symptoms at end of life (EOL) is
      described for cancer patients, but few articles focused on nononcological
      conditions. Decision making at EOL is commonly discussed with families but
      children are less frequently involved. SUMMARY: A thorough search of databases
      was conducted for articles published in the last year. We found few articles
      describing EOLC-S as a last resort. But how, when and by whom a symptom is
      defined as refractory, is not well established. Aggressive symptom management at
      EOL along with advanced care planning conducted by pediatric palliative care
      teams could diminish EOLC-S. More research is needed.

PMID- 21734585
TI  - Supportive and palliative care for adults dying from congenital heart defect.
AB  - PURPOSE OF REVIEW: Adult survivors with congenital heart disease (CHD) are a
      novel group of adults with chronic disease. Due to the nature of their surgical
      repair, the majority is not cured. This review focuses on changing demographics
      and mortality of adults with CHD, available knowledge and data on end-of-life
      (EOL) and palliative care in this patient group and outlines needs for future
      clinical practice and research. RECENT FINDINGS: Recent findings underscore that
      survival to adulthood has become the rule for the majority of patients born with
      CHD. Many remain at increased risk of premature death from their disease. Chronic
      circulatory failure has been identified as one of the leading causes of death
      and, thus, patients may benefit from incorporation of palliative care principles
      in their management. Recent studies show that this practice has not yet been
      widely adopted. Nonetheless a survey of adult outpatients has shown that many
      patients prefer to be involved in EOL decisions early in the course of their
      disease. SUMMARY: More research is needed to learn how we can best implement
      principles of palliative care in the growing population of adult survivors with
      CHD. This includes improved communication about EOL issues and a more
      comprehensive approach for symptom control.

PMID- 21734586
TI  - Recent advances in second-line treatment of castration-resistant prostate cancer.
AB  - PURPOSE OF REVIEW: Patients with metastatic castration-resistant prostate cancer
      (CRPC) no longer responsive to docetaxel have a poor prognosis, worsened quality
      of-life, and traditionally few options for treatment. This review addresses
      promising and practice-changing developments for the treatment of CRPC in the
      second-line setting. RECENT FINDINGS: Recent data for cabazitaxel, a novel taxane
      chemotherapy, and abiraterone acetate, a novel inhibitor of androgen synthesis,
      demonstrate significant improvements in the survival of patients with docetaxel
      refractory CRPC. We review the mechanisms of action of these agents and data from
      phase III clinical trials, contextualizing their place in therapy. We also update
      other areas of investigation, including oral platinum analogues, vascular
      endothelial growth factor receptor targeted therapy, inhibitors of chaperone
      proteins, and androgen receptor antagonists. SUMMARY: Upon disease progression
      after first-line docetaxel chemotherapy, cabazitaxel and abiraterone improve
      survival of patients with CRPC and are important novel treatment options.
      Potential toxicity from cabazitaxel necessitates careful patient selection and
      supportive care. Both abiraterone and cabazitaxel are also being evaluated in the
      first-line setting, and therefore the optimal sequencing of therapies remains
      uncertain. Many other novel agents continue to be evaluated and promising classes
      of agents include antisense oligonucleotides against clusterin (custirsen) and
      androgen receptor antagonists (MDV3100).

PMID- 21734587
TI  - Sleep patterns in late pregnancy and risk of preterm birth and fetal growth
      restriction.
AB  - BACKGROUND: During pregnancy, women are at particular risk for sleep deprivation
      and snoring because of the physiologic and hormonal changes of pregnancy. There
      is limited evidence for the association between sleep patterns in pregnancy and
      adverse birth outcomes. We examined the association of sleep duration and snoring
      in late pregnancy with the risk of preterm birth and fetal growth restriction.
      METHODS: We used data from the prospective mother-child cohort "Rhea" study in
      Crete, Greece 2007-2009. The analysis included 1091 women with singleton
      pregnancies, providing complete data on sleeping habits at the third trimester of
      gestation and birth outcomes. Fetal growth restriction was based on a customized
      model, and multivariate log-binomial regression models were used to adjust for
      confounders. RESULTS: Women with severe snoring were at high risk for low birth
      weight (relative risk = 2.6 [95% confidence interval = 1.2-5.4]), and fetal
      growth-restricted neonates (2.0 [1.0-3.9]) after adjusting for maternal age,
      education, smoking during pregnancy, and prepregnancy body mass index (BMI).
      Women with sleep deprivation (<=5 hours sleep) were at high risk for preterm
      births (1.7 [1.1-2.8]), with the highest risk observed for medically indicated
      preterm births (2.4 [1.0-6.4]) after adjusting for maternal age, education,
      parity, smoking during pregnancy, and prepregnancy BMI. CONCLUSIONS: These
      findings suggest that women with severe snoring in late pregnancy have a higher
      risk for fetal-growth-restricted neonates; and women with sleep deprivation have
      a higher risk for preterm births. The mechanisms underlying these associations
      remain unclear.

PMID- 21734588
TI  - Efficacy of pregabalin in preventing relapse in patients with generalized social
      anxiety disorder: results of a double-blind, placebo-controlled 26-week study.
AB  - The objective of this study was to evaluate the efficacy and safety of pregabalin
      in preventing relapse in generalized social anxiety disorder (SAD). Patients with
      Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)
      generalized SAD, who met responder criteria after 10 weeks of open-label
      treatment with fixed-dose pregabalin (450 mg/day; n=153), were randomly assigned
      to 26 weeks of double-blind treatment with pregabalin (450 mg/day) or placebo.
      The primary a-priori outcome of time to relapse was analyzed using the Kaplan
      Meier method and the log-rank test. Double-blind treatment with pregabalin was
      associated with significant delay in time to relapse versus placebo (P=0.035),
      and with significantly greater maintenance of symptomatic improvement over 26
      weeks on the Liebowitz Social Anxiety Scale total (P=0.012) and subscale scores
      and on the Marks Fear Questionnaire total phobia (P=0.010) and social phobia
      (P=0.014) subscales. Pregabalin was generally well tolerated. During the double
      blind phase, the adverse events that occurred more frequently with pregabalin
      compared with placebo were dizziness (11.3 vs. 4.1%) and infection (21.3 vs.
      16.4%). The results of this study suggest that pregabalin (450 mg/day) is safe,
      well tolerated, and has significant relapse-prevention efficacy over 26 weeks in
      patients with SAD who responded to an initial course of the pregabalin treatment.

PMID- 21734589
TI  - The metabolic fitness program: lifestyle modification for the metabolic syndrome
      using the resources of cardiac rehabilitation.
AB  - PURPOSE: To describe and assess the effectiveness of a lifestyle intervention
      program (Met Fit) designed to treat the metabolic syndrome (MetSyn) in a cardiac
      rehabilitation setting. METHODS: Met Fit is a physician referred and patient pay
      ($350) program consisting of 12 weekly sessions of 45 minutes of exercise and 45
      minutes of education with target exercise recommendations of 150 to 200 minutes
      weekly and 5% loss in body weight using a Mediterranean-style diet. Primary
      outcomes are compliance with program recommendations and secondary outcomes
      effecting MetSyn components. RESULTS: Patients (N = 126) were enrolled between
      June 2005 and July 2009 averaging 9 per class. Mean (SD) age was 51(12) years,
      body mass index 38(6.9) kg/m, high density lipoprotein-cholesterol for men
      37(9.4) mg/dL and women 46(10) mg/dL, glucose 121(39) mg/dL, and homeostatic
      model assessment of insulin resistance 7.2(6.1). For the 93 (73.8%) patients for
      whom there was complete data, mean weight loss was 6.2(6.9) lbs, [corrected]
      63.4% lost at least 4 lbs, [corrected] and 19.4% lost more than 5% of weight.
      Significant reductions were observed in the waist circumference and body fat, and
      systolic and diastolic blood pressure. Triglycerides decreased significantly in
      both diabetics and nondiabetics but glucose decreased significantly only in
      diabetics. At baseline, 51% had evidence of depression, which decreased to 24.7%
      at 12 weeks. At program completion, 18 patients (19.4%) no longer had the MetSyn
      and 39 (41.9%) lost at least 1 criterion (P < .0001). CONCLUSIONS: A 12-week
      patient-pay lifestyle interventional program conducted in a cardiac
      rehabilitation setting can result in a highly significant benefit to patients
      with the MetSyn.

PMID- 21734590
TI  - Psychoeducational rehabilitation for health behavior change in coronary artery
      disease: a systematic review of controlled trials.
AB  - PURPOSE: Psychoeducation is a recommended component of cardiac rehabilitation,
      but to date, evidence from high quality trials examining behavior change has not
      been synthesized. The primary aim of this systematic review was to examine the
      effectiveness of psychoeducation on behavior change in adults with coronary
      artery disease participating in cardiac rehabilitation; and to identify if
      changes in health behavior had an effect on modifiable physiological risk
      factors. METHODS: A search of electronic databases was conducted for randomized
      controlled trials involving adults with a primary diagnosis of myocardial
      infarction, coronary artery bypass graft surgery, percutaneous coronary
      intervention, stable angina, or coronary artery disease defined by angiography.
      Trials comparing psychoeducational programs to exercise only, standard cardiac
      rehabilitation or medical care were included. Primary outcomes were smoking
      status, physical activity, dietary habits, supplemental oxygen, or medication
      use. Included trials were assessed for quality with the PEDro scale, and data
      synthesized descriptively or with meta-analysis. RESULTS: Six randomized
      controlled trials and 1 quasiexperimental trial were included, a total of 536
      participants. A meta-analysis from 213 participants showed psychoeducational
      interventions produced a significant positive effect on physical activity levels
      over the medium term (6-12 months) when compared with exercise and risk factor
      education, (delta = .62, 95% CI 0.3-0.94). However, there was limited positive
      evidence for change in smoking and dietary behavior. No effect was found on
      physiological risk factors. CONCLUSIONS: Psychoeducational interventions produce
      a significant positive effect on physical activity levels and potentially on
      dietary habits and smoking. Strategies such as goal setting, problem solving,
      self-monitoring, and role modeling appear to be influential in this change.

PMID- 21734591
TI  - Maximal oxygen uptake is lower for a healthy Indian population compared to white
      populations.
AB  - PURPOSE: Presently used prediction equations for maximal oxygen uptake are mostly
      derived from studies of western populations. However, the interracial differences
      are quite large when prediction equations for the Western-white population are
      applied to Asian-Indians. The present study was aimed at the initial development
      of a prediction equation for the healthy sedentary Indian participants using
      symptom limited graded incremental exercise testing and to compare the new
      regression equation to other published data. METHODS: Participants were staff and
      caregivers of patients from different states of India. All participants completed
      a maximal graded exercise test on a motorized treadmill at Christian Medical
      College, Vellore, Tamil Nadu to determine maximal oxygen uptake (VO(2)max).
      RESULTS: Predictive equations for both men and women were obtained from multiple
      linear regression analysis and significant correlations were found for weight and
      height. The correlation coefficients of the new regression equations with
      measured VO(2)max of study population were R(2) = .511 for men and R(2) = .656
      for women. These were compared with other published equations with differences
      ranging from 7% to 50% for men and 10% to 36% for women. CONCLUSIONS: The present
      study derived a prediction equation for VO(2)max applicable to the Asian-Indian
      population. The predicted maximal oxygen uptake of the study population using the
      new equation is significantly lower than the white population. The new equation
      may facilitate more meaningful interpretation of the test data in this population
      and possibly a wider use.

PMID- 21734592
TI  - Correlation between filtering bleb morphology, expression of inflammatory marker
      HLA-DR by ocular surface, and outcome of trabeculectomy.
AB  - PURPOSE: To correlate clinical bleb characteristics and the expression of human
      leukocyte antigen (HLA)-DR by conjunctiva with the outcome of trabeculectomy.
      PATIENTS AND METHODS: In this cross-sectional study, bleb morphology was assessed
      at slit lamp using the Moorfields Bleb Grading System in 85 eyes of 85 patients.
      Conjunctival specimens were collected from superior conjunctiva by impression
      cytology and analyzed for the expression of HLA-DR on epithelial and antigen
      presenting cells. The success of trabeculectomy was defined as intraocular
      pressure <21 mm Hg without antiglaucoma drops. Differences in bleb
      characteristics and expression of HLA-DR between eyes with surgical success and
      failure were examined. RESULTS: Fifty-eight of 85 eyes with successful
      trabeculectomy had significantly greater central and maximal area of the bleb
      (P<0.001) with decreased vascularity of the central (P=0.02) and peripheral part
      of the bleb (P=0.03). The expression of HLA-DR on conjunctival epithelial cells
      and antigen-presenting cells was not different between the eyes with successful
      and failed trabeculectomy and also not between the eyes with and without topical
      glaucoma medication or topical corticosteroid eye drops. CONCLUSIONS: Successful
      trabeculectomy was associated with greater area and decreased vascularity of the
      bleb but not with diminished expression of inflammatory marker by ocular surface.
      Presence of subclinical inflammation in eyes without eye drops may result from
      the transcellular aqueous pathway towards the ocular surface, especially in
      functioning blebs with adjunctive mitomycin C.

PMID- 21734593
TI  - Assessment of corneal biomechanical properties in normal tension glaucoma and
      comparison with open-angle glaucoma, ocular hypertension, and normal eyes.
AB  - PURPOSE: To assess the biomechanical properties of corneas in patients with
      normal tension glaucoma (NTG) and to compare them with those of patients with
      primary open-angle glaucoma (POAG), ocular hypertension (OHT), and normal
      controls (N). METHODS: Corneal hysteresis (CH), corneal resistance factor (CRF),
      Goldmann intraocular pressure (IOPg), and corneal compensated IOP (IOPcc) were
      obtained using an ocular response analyzer for 28 eyes in 14 patients with NTG,
      75 eyes in 38 patients with chronic POAG, 53 eyes of 27 patients with OHT, and 44
      eyes of 22 N controls. IOP using Goldmann applanation tonometry (IOPGA) and
      ultrasonic central corneal thickness (CCT) were also measured for each eye.
      Analysis of variance test was used for statistical analysis. RESULTS: CH was
      significantly lower in the NTG group (9.88+/-2.02 mm Hg) compared with the N
      group (11.05+/-1.53 mm Hg; P<0.01). CRF was significantly lower in the NTG group
      (9.5+/-1.89 mm Hg) compared with the POAG group (11.15+/-2.35 mm Hg; P<0.01) and
      to the N group (11.00+/-1.75 mm Hg; P<0.01). CCT was not considered significantly
      different between the 4 groups. However, IOPcc was found to be significantly
      lower in NTG group compared with the POAG group and OHT group (P<0.001).
      CONCLUSION: NTG was associated with significantly lower CRF than chronic POAG and
      N patients. CH and CRF could be a useful tool in early diagnosis of NTG.

PMID- 21734594
TI  - Does an association exist between pseudoexfoliation syndrome and chronic kidney
      disease?
AB  - PURPOSE: To determine whether pseudoexfoliation (PEX) syndrome is associated with
      an increased risk of chronic kidney disease (CKD). PATIENTS AND METHODS: In this
      cross-sectional study, 271 consecutive patients were recruited into 3 study
      groups---PEX syndrome (n=86), primary open-angle glaucoma (POAG) (n=91), and
      nonglaucoma controls (n=94)---and underwent serum creatinine testing to determine
      their glomerular filtration rates (eGFR). Repeat eGFR and testing for urine
      albumin:creatinine ratio were performed a minimum of 3 months later if the
      initial eGFR was less than 60 mL/min/1.73 m. CKD was diagnosed if both eGFR
      levels were less than 45 mL/min/1.73 m or both eGFR levels were less than 60
      mL/min/1.73 m and the urine albumin:creatinine ratio was greater than 2.0. The
      main outcome measure was the rate of CKD for each group. RESULTS: The CKD rate
      for the control group (11.7%, 11 of 94) was statistically higher than the PEX
      (3.5%, 3 of 86, P=0.050) and the POAG (3.3%, 3 of 91, P=0.049) groups. However,
      there was a significantly higher rate of diabetes mellitus, a known risk factor
      for CKD, in the control group than the PEX and POAG groups. After adjusting for
      the differences in the rate of diabetes mellitus and mean age (another risk
      factor for CKD) between groups, a multivariate logistic regression analysis
      showed that none of the study groups was a predictor of an increased rate of CKD.
      A post-hoc analysis performed with all patients with diabetes mellitus removed
      also showed no statistical difference between groups for CKD rates and mean eGFR
      levels. CONCLUSIONS: Compared with age-matched patients with POAG and nonglaucoma
      controls, PEX syndrome was not found to be associated with an increased
      prevalence of CKD.

PMID- 21734595
TI  - Leber hereditary optic neuropathy mimicking neuromyelitis optica.
AB  - Leber hereditary optic neuropathy (LHON) is rarely associated with multiple
      sclerosis-like features. We present a case of a 65-year-old African American
      woman with LHON masquerading as neuromyelitis optica (NMO). We highlight the
      features of the clinical examination and MRI that were suggestive of an
      alternative diagnosis and review the literature regarding LHON and multiple
      sclerosis. The diagnosis of LHON should be considered in all cases of acute or
      subacute bilateral optic neuropathy, including presumed seronegative NMO.

PMID- 21734596
TI  - Comparison of 10-mg doses of 4-aminopyridine and 3,4-diaminopyridine for the
      treatment of downbeat nystagmus.
AB  - OBJECTIVE: Animal experiments have demonstrated that aminopyridines increase
      Purkinje cell excitability, and in clinical studies, 4-aminopyridine (4-AP) and
      3,4-diaminopyridine (3,4-DAP) improved downbeat nystagmus. In this double-blind,
      prospective, crossover study, the effects of equivalent doses of 4-AP and 3,4-DAP
      on the slow-phase velocity (SPV) of downbeat nystagmus were compared. METHODS:
      Eight patients with downbeat nystagmus due to different etiologies (cerebellar
      degeneration [n = 1], bilateral vestibulopathy [n = 1], bilateral vestibulopathy
      and cerebellar degeneration [n = 1], Arnold-Chiari I malformation and cerebellar
      ataxia [n = 1], cryptogenic cerebellar ataxia [n = 4]) were included. They were
      randomly assigned to receiving a single capsule of 10 mg of 3,4-DAP or 4-AP
      followed by 6 days with no medication. One week later, the treatment was
      switched, that is, 1 single capsule (10 mg) of the other agent. Recordings with 3
      dimensional video-oculography were performed before and 45 and 90 minutes after
      drug administration. RESULTS: Both medications had a significant effect
      throughout time (pre vs post 45 vs post 90) (F() = 8.876; P < 0.01). Following
      the administration of 3,4-DAP, mean slow velocity decreased from -5.68 degrees /s
      (pre) to -3.29 degrees /s (post 45) to -2.96 degrees /s (post 90) (pre vs post
      45/post 90 P < 0.01). In 4-AP, the mean SPV decreased from -6.04 degrees /s (pre)
      to -1.58 degrees /s (post 45) to -1.21 degrees /s (post 90) (pre vs post 45/post
      90 P < 0.00001). Both after 45 and after 90, the mean SPVs were significantly
      lower for 4-AP than for 3,4-DAP (P < 0.05). None of the patients reported serious
      side effects. CONCLUSION: Based on these results, 10-mg doses of 4-AP lead to a
      more pronounced decrease of the SPV of downbeat nystagmus than do equivalent
      doses of 3,4-DAP.

PMID- 21734597
TI  - Hourly rounding: challenges with implementation of an evidence-based process.
AB  - Introduction of an evidence-based practice change, such as hourly rounding, can
      be difficult in the hospital setting. This study used ethnographic methods to
      examine problems with the implementation of hourly rounding on 2 similar
      inpatient units at our hospital. Results indicate that careful planning,
      communication, implementation, and evaluation are required for successful
      implementation of a nursing practice change.

PMID- 21734598
TI  - Improving nursing satisfaction and quality through the creation of admission and
      discharge nurse team.
AB  - The admission and discharge (AD) process involves a significant amount of nursing
      time. The organization explored the use of an AD nurse team on the basis on
      recommendations from the organization's aging nurse workforce and in an effort to
      provide bedside nurses more time in direct patient care. A pre-post design was
      used to evaluate the intervention. Postimplementation patient and nurse
      satisfaction and the quality of the AD process significantly improved. Findings
      support the use of an AD team as a method to improve patient and nurse
      satisfaction and nursing documentation and promote retention of older nurses.

PMID- 21734599
TI  - Do oro-anal transit markers predict which children would benefit from colonic
      manometry studies?
AB  - OBJECTIVES: The aim of the study was to compare oro-anal transit time (OTT)
      measured by radio-opaque markers with colon motility (CM) findings in children
      with chronic constipation and to assess clinical outcomes in children with
      chronic constipation evaluated by OTT and CM studies. METHODS: Twenty-four
      children with chronic constipation (12 girls; median age 12 years [3-18 years];
      median symptoms 87 months [6-186 months]) who underwent OTT and CM studies were
      reviewed. The OTT was determined using commercially available Sitzmarks. Patients
      were studied for a median of 23 months (4-60 months) and outcomes reviewed.
      RESULTS: All 5 children with normal OTT had normal CM; however, only 47% (9/19)
      of children with slow OTT had an abnormal CM. The abnormal CM findings were total
      colonic pseudo-obstruction in 3 and left colonic pseudo-obstruction in 6
      children. Of the 9 children with abnormal CM, 5 were managed surgically, 1 with
      medicine escalation, and 3 were lost to follow-up; all 6 children with known
      follow-up have more bowel movements and less soiling. Of the 15 children with
      normal CM, 10 were managed with medication escalation, 3 with behavioral
      intervention, and 2 surgically. Of these 15 children, 8 improved, 1 did not
      change, 2 worsened, and 4 were lost to follow-up. CONCLUSIONS: OTT studies may be
      helpful to predict which children should be referred for CM studies. Normal OTT
      studies may predict normal colon manometry; however, abnormal OTT studies may not
      predict abnormalities in colonic manometry in children with chronic constipation.
      Therefore, patients with slow transit marker studies should be assessed by colon
      manometry to evaluate colon neuromuscular integrity.

PMID- 21734600
TI  - Treatment of acute diarrhea with Saccharomyces boulardii in infants.
AB  - OBJECTIVE: The aim of the study was to determine whether an oral treatment with a
      commercial pharmaceutical product containing Saccharomyces boulardii would reduce
      the duration of diarrhea in infants with acute diarrhea. PATIENTS AND METHODS: In
      the present double-blind, placebo-controlled study, 186 infants, 6 to 48 months
      old and hospitalized within 72 hours after the onset of acute diarrhea in 2
      hospitals in Goiania, Goias, Brazil, were randomly assigned to receive twice per
      day for 5 days 200 mg of a commercial pharmaceutical product containing 4 * 10
      viable cells of S boulardii or a placebo. Stool samples were submitted to search
      for rotavirus. Among the 176 infants who completed the trial, those treated with
      S boulardii (90) showed a reduction in diarrhea duration (P < 0.05) when compared
      with the placebo group (86). RESULTS: The present study shows a reduction in
      diarrhea duration when S boulardii was given to children within 72 hours after
      the onset of acute diarrhea. CONCLUSIONS: The present study suggests a
      complementary treatment of acute diarrhea in infants with daily oral doses of S
      boulardii.

PMID- 21734601
TI  - Ingredients other than noni may be culprits in acute hepatotoxicity in 14-year
      old boy.

PMID- 21734603
TI  - Helicobacter pylori eradication: can't we do better?

PMID- 21734604
TI  - Pyrosequencing-based molecular monitoring of the intestinal bacterial
      colonization in preterm infants.
AB  - OBJECTIVES: The aim of the study was to investigate the previously unexplored
      diversity of neonatal intestinal microbiota and monitor early intestinal
      colonization patterns in Korean preterm infants using high-throughput
      pyrosequencing technology combined with 16S rDNA-based molecular methods.
      SUBJECTS AND METHODS: A total of 46,369 partial 16S rDNA sequences obtained from
      30 fecal samples serially taken from 10 very-low-birth weight preterm infants
      were analyzed. RESULTS: A significant proportion of the molecular species (21.9%)
      was found to be unclassified. The pathogenic or potentially pathogenic molecular
      species belonging to the classes Gammaproteobacteria and Bacilli were predominant
      during the entire observation period. Anaerobic or nonpathogenic molecular
      species belonging to the class Clostridia (except Clostridium difficile) and
      phyla Bacteroidetes were ubiquitous even within 72 hours after birth. The
      proportion of these species increased significantly at 1 month of age. The most
      ubiquitous and abundant major molecular genera common to all of the postnatal
      ages were Escherichia, Enterobacter, Enterococcus, Veillonella, Serratia,
      Staphylococcus, Roseburia, Acinetobacter, Citrobacter, Bacteroides,
      Faecalibacterium, Blautia, and Streptococcus. CONCLUSIONS: The diversity and
      dynamic nature of intestinal bacterial colonization in very-low-birth weight
      preterm infants were revealed using pyrosequencing technology. The results of the
      present pilot study may provide a basis to consider when investigating or
      interpreting the role of intestinal microbiota in certain preterm infant diseases
      such as necrotizing enterocolitis or systemic infection.

PMID- 21734605
TI  - What do changes in prematch vs. postmatch, 1, 2, and 3 days postmatch body weight
      tell us about fluid status in English Premiership rugby union players?
AB  - This study investigated changes in body weight pre and postmatch and 1, 2, and 3
      days postmatch. Thirty-six players contracted to an English Premiership rugby
      union club had their pre and postmatch body weight and 1, 2, and 3 day postmatch
      body weight recorded across 14 matches played (10 at home and 4 away) during the
      official 2003-2004 professional rugby union season, representing a total of 262
      player appearances. Body weight was recorded using a set of calibrated Seca
      digital scales with players wearing underwear only and toweled dry of all sweat
      (postmatch). Players were allowed to ingest fluid ad libitum throughout each
      match. A number of players recorded pre to postmatch reductions of body weight of
      >2% with some as high as 4.9%. Significant position-specific mean reductions in
      prematch to postmatch body weight (+/-SD) were found for both forwards (1.94 +/-
      0.14 kg) and backs (1.04 +/- 0.17 kg). The mean gain in postmatch to 1-day
      postmatch body weight was significant for forwards (1.40 +/- 0.27 kg) but not for
      backs (0.76 +/- 0.30 kg). There were no significant mean differences between
      prematch and 2 or 3 days postmatch body weight for either forwards or backs.
      Forwards on average lost a significantly greater proportion of their weight pre
      to postmatch than backs (p = 0.005). Forwards were on average 99.5% of the
      prematch weight at 1 day postmatch, whereas backs were 99.7% (p = 0.598).
      Forwards were 99.6% of their prematch weight at 3 days postmatch, whereas backs
      were 100.4% (p = 0.035). Changes in fluid status can be effectively monitored by
      recording changes in body weight and is useful where players are undertaking
      training sessions within 1, 2, or 3 days after their last match as a measure of
      rehydration status.

PMID- 21734606
TI  - The effect of combined exercise training in adolescents who are overweight or
      obese with intellectual disability: the role of training frequency.
AB  - Data about effects of exercise training in adolescents with intellectual
      disability (ID) are very limited. This study investigated the effect of 2
      different frequencies of the same intensity and total training volume of combined
      exercise training on indices of body composition, physical fitness, and lipid
      profile in overweight and obese adolescents with ID. A total of 45 overweight and
      obese adolescents with ID aged 14-22 years with a total IQ 45-70 received
      combined exercise training 3 times a week (CET3) for 30 sessions (10 weeks; n =
      15), twice a week (CET2) for 30 sessions (15 weeks; n = 15), or no training (10
      weeks; n = 15). Groups were matched for age, sex, and education form. Before and
      after the intervention period, indices of body composition, physical fitness and
      lipid profile have been evaluated. Compared to the control group, CET3 resulted
      in a significant improvement of physical fitness, obesity indices, and lipid
      profile of the participants. Comparing CET2 with CET3, no significantly different
      evolutions were noticed, except for lower limb strength in favor of exercising 3
      times a week. In conclusion, exercising 2 times a week, which is more feasible
      and practical for participants and guidance, has the same health beneficial
      effects as 3 times per week in overweight and obese adolescents with ID in short
      term training.

PMID- 21734607
TI  - Histone H3 phosphoacetylation is critical for heroin-induced place preference.
AB  - We investigated the role of histone H3 phosphoacetylation in the nucleus
      accumbens (NAc) in heroin-conditioned place preference paradigm. Heroin could
      dose-dependently increase histone H3 phosphoacetylation specifically in the NAc
      and could enhance heroin place preference. Injection of trichostatin A into the
      NAc significantly augmented heroin-induced histone H3 phosphoacetylation and
      enhanced heroin place preference. Conversely, injection of MK-801 into the NAc
      attenuated histone H3 phosphoacetylation and reduced heroin place preference.
      These data suggest that histone H3 phosphoacetylation in the NAc may play a
      critical role in heroin addiction.

PMID- 21734608
TI  - Retinal amyloid peptides and complement factor H in transgenic models of
      Alzheimer's disease.
AB  - Murine transgenic models of Alzheimer's disease (Tg-AD) have been useful to
      analyze the contribution of beta-amyloid precursor protein (betaAPP), Abeta42
      peptide deposition, and the proinflammatory mechanisms that characterize
      Alzheimer-type neuropathology. In this report, we have studied the levels of
      betaAPP, Abeta40 and Abeta42 peptide, as well as the innate immune and
      inflammatory response-regulator complement factor H in the brain and retina in
      four different Tg-AD models including Tg2576, PSAPP, 3xTg-AD, and 5xFAD. Aged,
      symptomatic 5xFAD mice showed the highest retinal abundance of Abeta42 peptides
      and the highest deficits in complement factor H. This may be a useful model to
      study the mechanisms of amyloid-mediated inflammatory degeneration. The superior
      colliculus and retina obtained from late-stage Alzheimer's disease revealed
      upregulated amyloidogenic and inflammatory signaling along the anteroposterior
      axis of the retinal-primary visual cortex pathway.

PMID- 21734609
TI  - Different representations of tooth chatter and purr call in guinea pig auditory
      cortex.
AB  - Multielectrode arrays were used to compare responses to tooth chatter and purr
      calls from all eight areas of the auditory cortex in anaesthetized guinea pigs.
      These calls have different behavioural contexts: males emit tooth chatters in
      aggressive encounters and the purr call during courtship behaviour. Of the two
      core areas, the primary auditory cortex responded better to both signals than the
      dorsocaudal core area. Of the six belt areas, the ventral transition area was
      found to be exceptionally sensitive to tooth chatter and less responsive to purr.
      The small rostral field responded faithfully to the purr, but not to tooth
      chatter, and ventrorostral belt often showed on/off responses; other belt areas
      were unresponsive.

PMID- 21734610
TI  - Phenylketonuria-related synaptic changes in a BTBR-Pah(enu2) mouse model.
AB  - Phenylketonuria is the most common, inherited aminoacidopathy associated with
      brain injury. To date, no study has focused on the neuropathology of the genetic
      mouse model of phenylketonuria, BTBR-Pah(enu2). We examined dendritic spines and
      synapses in the CA1 and prefrontal cortex among the wild-type, heterozygous, and
      BTBR-Pah(enu2) mice. A reduced density of dendritic spines, a shortened length of
      the presynaptic active zone, a widened synaptic cleft, and decreased thickness of
      postsynaptic density were revealed in BTBR-Pah(enu2) mice. Meanwhile, the
      phosphorylation at Thr286 of Ca(2+)/calmodulin-dependent protein kinase IIalpha
      was alerted in BTBR-Pah(enu2) mice. These findings revealed that phenylketonuria
      related brain impairment is accompanied with abnormalities of dendritic spines
      and synapses. The dysfunction of Ca(2+)/calmodulin-dependent protein kinase
      IIalpha may result in an impaired synaptic function.

PMID- 21734611
TI  - Direct activation of guinea pig vagal afferent neurons by FMRFamide.
AB  - Vagus nerve comprises two distinct kinds of nerves, nodose and jugular ganglionic
      nerves. We tested pharmacological difference between two vagal nerves in the
      responsiveness to FMRFamide. The response probability to FMRFamide was
      significantly higher in nodose than jugular nerves in intracellular calcium
      measurement. Nodose nerves also depolarized membrane potential to FMRFamide more
      than jugular nerves did, in patch-clamp recording, although the probability of
      action potential discharge was same in both nerves. The inward current induced by
      FMRFamide was characterized as mixed cations. These results suggest that
      FMRFamide may act as an activator and modulator of vagal sensory nerves for
      treating symptoms in visceral diseases.

PMID- 21734612
TI  - Early attention modulates perceptual interpretation of multisensory stimuli.
AB  - Perceptual interpretation of the same multisensory stimuli may rely upon
      influence of attention on multisensory integration. We tested this hypothesis by
      recording the brain activity using magnetoencephalography in a passing-bouncing
      illusion with sound. Early activation of the attention-related brain areas and
      subsequent involvement of the multisensory areas were associated with the
      bouncing percept. Early activation of the unimodal sensory areas and later
      involvement of the attention-related areas were associated with the passing
      percept. Thus, the bouncing percept occurs when early attentional deployment
      facilitates multisensory integration modulating visual perception. The passing
      percept results from hierarchical sequence of the perceptual processes: early
      activation of the unimodal areas and late attentional deployment. Alternation of
      the perceptual interpretations may depend on spontaneous fluctuation of
      attention.

PMID- 21734613
TI  - The effect of complement C5a on mitochondrial functions of PC12 cells.
AB  - C5a is thought to play a role during complement-activated neuronal apoptotic cell
      death in the central nervous system. The mechanisms responsible are however not
      well-understood. As mitochondria play a key role during apoptosis, we
      investigated mitochondria as a potential target for C5a. Using PC12 cells, we
      demonstrated that exposure to C5a led to inhibition of mitochondrial respiration,
      dehydrogenase and cytochrome c oxidase activities. Interestingly, an increase in
      expression of the mitochondrial stress protein chaperonin 60 was also observed,
      confirming a marked effect of C5a on mitochondrial functions. These observations
      are the first documented intracellular effects noted for the complement molecule
      C5a in in-vitro cultured cells.

PMID- 21734614
TI  - Giant intracranial aneurysms:  evolution of management in a contemporary surgical
      series.
AB  - BACKGROUND: Many significant microsurgical series of patients with giant
      aneurysms predate changes in practice during the endovascular era. OBJECTIVE: A
      contemporary surgical experience is presented to examine changes in management
      relative to earlier reports, to establish the role of open microsurgery in the
      management strategy, and to quantify results for comparison with evolving
      endovascular therapies. METHODS: During a 13-year period, 140 patients with 141
      giant aneurysms were treated surgically. One hundred aneurysms (71%) were located
      in the anterior circulation, and 41 aneurysms were located in the posterior
      circulation. RESULTS: One hundred eight aneurysms (77%) were completely occluded,
      14 aneurysms (10%) had minimal residual aneurysm, and 16 aneurysms (11%) were
      incompletely occluded with reversed or diminished flow. Three patients with
      calcified aneurysms were coiled after unsuccessful clipping attempts. Eighteen
      patients died in the perioperative period (surgical mortality, 13%). Bypass
      related complications resulted from bypass occlusion (7 patients), aneurysm
      hemorrhage due to incomplete aneurysm occlusion (4 patients), or aneurysm
      thrombosis with perforator or branch artery occlusion (4 patients). Thirteen
      patients were worse at late follow-up (permanent neurological morbidity, 9%; mean
      length of follow-up, 23 +/- 1.9 months). Overall, good outcomes (Glasgow Outcome
      Score 5 or 4) were observed in 114 patients (81%), and 109 patients (78%) were
      improved or unchanged after therapy. CONCLUSION: A heavy reliance on bypass
      techniques plus indirect giant aneurysm occlusion distinguishes this contemporary
      surgical experience from earlier ones, and obviates the need for hypothermic
      circulatory arrest. Experienced neurosurgeons can achieve excellent results with
      surgery as the "first-line" management approach and endovascular techniques as
      adjuncts to surgery.

PMID- 21734615
TI  - Posterior fossa exploration for trigeminal neuralgia patients older than 70 years
      of age.
AB  - BACKGROUND: Patients with medically unresponsive trigeminal neuralgia (TN) who
      are >70 years of age often undergo operations that typically provide pain relief
      for <5 years despite having a life expectancy that can exceed 15 years.
      OBJECTIVE: To review the safety and efficacy of posterior fossa exploration (PFE)
      for TN patients > 70 years of age. METHODS: From 1999 to 2009, 67 TN patients >70
      years of age (median, 74 years) underwent a PFE. Thirty-seven patients (55%) had
      failed >= 1 prior surgeries (median, 2). Fifty-nine patients (88%) had a
      microvascular decompression, and 8 patients (12%) underwent a partial sensory
      rhizotomy. Follow-up (median, 40 months) was censored at the time of last contact
      (n = 51), additional surgery (n = 12), or death (n = 4). RESULTS: Complete pain
      relief (no pain, no medications) was 87% at 1 year and 78% at 5 years. Facial
      pain outcomes did not correlate with patient age, sex, prior surgery, or pain
      duration. Postoperative complications were noted in 10 patients (15%) and
      included ataxia (10%), hearing loss (5%), trigeminal dysesthesias (5%), facial
      weakness (3%), aseptic meningitis (2%), and pulmonary embolus (2%). Factors
      associated with postoperative complications were prior PFE (P = .01) and
      neurovascular compression from a dolicoectatic basilar artery (P = .03).
      CONCLUSION: Posterior fossa exploration is safe and effective for physiologically
      healthy TN patients >70 years of age. It should be deferred in older patients
      with TN secondary to a dolicoectatic basilar artery and patients who have
      persistent/recurrent pain after a previous PFE unless simpler procedures prove
      ineffective at controlling their facial pain.

PMID- 21734616
TI  - Accuracy of image-guided pedicle screw placement using intraoperative computed
      tomography-based navigation with automated referencing. Part II: thoracolumbar
      spine.
AB  - BACKGROUND: Image-guided spinal instrumentation may reduce complications in
      spinal instrumentation. OBJECTIVE: To assess accuracy, time efficiency, and staff
      radiation exposure during thoracolumbar screw instrumentation guided by
      intraoperative computed tomography (iCT)-based neuronavigation (iCT-N). METHODS:
      In 55 patients treated for idiopathic and degenerative deformities, 826 screws
      were inserted in the thoracic (T2-T12; n = 243) and lumbosacral (L1-S1; n = 545)
      spine, as well as ilium (n = 38) guided by iCT-N. Up to 17 segments were
      instrumented following a single automated registration sequence with the dynamic
      reference arc (DRA) uniformly attached to L5. Accuracy of iCT-N was assessed by
      calculating angular deviations between individual navigated tool trajectories and
      final implant positions. Final screw positions were also graded according to
      established classification systems. Clinical and radiological outcome was
      assessed at 12 to 14 months. RESULTS: Additional intraoperative fluoroscopy was
      unnecessary, eliminating staff radiation exposure. Unisegmental K-wire insertion
      required 4.6 +/- 2.9 minutes. Of the thoracic pedicle screws 98.4% were assigned
      grades I to III according to the Heary classification, with 1.6% grade IV
      placement. In the lumbar spine, 94.4% of screws were completely contained
      (Gertzbein classification grade 0), 4.6% displayed minor pedicle breaches <2 mm
      (grade 1), and 1% of lumbar screws deviated by >2 to <4 mm (grade 2). The
      accuracy of iCT-N progressively deteriorates with increasing distance from the
      DRA, but allows safe instrumentation of up to 12 segments. CONCLUSION: iCT-N
      using automated referencing allows for safe, highly accurate multilevel
      instrumentation of the entire thoracolumbosacral spine and ilium, rendering
      additional intraoperative imaging dispensable. In addition, automated
      registration is time-efficient and significantly reduces the need for re
      registration in multilevel surgery.

PMID- 21734617
TI  - Early breastfeeding experiences and postpartum depression.
AB  - BACKGROUND: The first weeks after childbirth are a critical period for mother and
      newborn. Women may present with lactation failure and postpartum depression. It
      is unclear how a woman's early breastfeeding experiences relate to postpartum
      depression. OBJECTIVE: We estimated the association between early breastfeeding
      experiences and postpartum depression at 2 months. METHODS: We modeled this
      association with logistic regression in a secondary analysis of data from the
      Infant Feeding Practices Study II. We assessed postpartum depression status with
      the Edinburgh Postnatal Depression Scale. RESULTS: In the neonatal period, 2,586
      women reported ever breastfeeding, among whom 223 (8.6%) met criteria for major
      depression (Edinburgh Postnatal Depression Scale 13 or greater) at 2 months
      postpartum. Women who disliked breastfeeding in the first week were more likely
      to experience postpartum depression at 2 months (odds ratio [OR] 1.42, 95%
      confidence interval [CI] 1.04-1.93) adjusting for maternal age, parity,
      education, ethnicity, and postnatal WIC participation. Women with severe
      breastfeeding pain in the first day (adjusted OR 1.96, 95% CI 1.17-3.29), the
      first week (adjusted OR 2.13, 95% CI 0.74-6.15 compared with no pain), and the
      second week (adjusted OR 2.24, 95% CI 1.18-4.26 compared with no pain) were more
      likely to be depressed. Breastfeeding help appeared protective among women with
      moderate (adjusted OR 0.22, 95% CI 0.05-0.94) or severe (adjusted OR 0.17, 95% CI
      0.04-0.75) pain with nursing. CONCLUSION: Women with negative early breastfeeding
      experiences were more likely to have depressive symptoms at 2 months postpartum.
      Women with breastfeeding difficulties should be screened for depressive symptoms.
      LEVEL OF EVIDENCE: II.

PMID- 21734618
TI  - Apgar scores at 5 minutes after birth in relation to school performance at 16
      years of age.
AB  - OBJECTIVE: To estimate the association between an Apgar score of less than 7 at 5
      minutes after birth and long-term cognitive function. METHODS: A linkage between
      the Swedish Medical Birth Registry and the Swedish School Grade Registry was
      performed. All singletons born from 1973 to 1986 after 36 6/7 weeks of gestation
      to Swedish-born women were included. Fetuses that were stillborn, newborns who
      had congenital malformations or were small for gestational age, and children who
      died or emigrated before 16 years of age were excluded from the analysis.
      RESULTS: The study included 877,618 individuals in the analysis. Newborns with
      Apgar scores less than 7 at 5 minutes after birth showed a significantly
      increased risk of never receiving graduation grades, presumably because they went
      to special schools because of cognitive impairment or other special educational
      needs (odds ratio 1.93, 95% confidence interval 1.75-2.14). One out of 44
      newborns (numbers needed to harm) with an Apgar score of less than 7 at 5 minutes
      after birth will go to a special school because of the antenatal or perinatal
      factors that caused the low Apgar score. Nearly all school children who had Apgar
      scores of less than 7 at 5 minutes after birth showed an increased risk of
      graduating from compulsory school without graduation grades in that specific
      subject or receiving the lowest possible grades and were also less likely to
      receive the highest possible grade. CONCLUSION: An Apgar score of less than 7 at
      5 minutes after birth is associated with subtle cognitive impairment, as measured
      by academic achievement at 16 years of age. LEVEL OF EVIDENCE: II.

PMID- 21734619
TI  - Neuroschistosomiasis due to Schistosoma haematobium presenting as spinal cord
      tumor.
AB  - Schistosomiasis is rarely encountered in the United States, but immigration and
      travel to endemic areas make it important to know its various presentations to
      improve diagnosis and treatment. We present our experience with a child with
      Schistosoma haematobium pseudotumor, initially diagnosed as a cord neoplasm.

PMID- 21734620
TI  - Antiretroviral therapy responses among children attending a large public clinic
      in Soweto, South Africa.
AB  - BACKGROUND: Antiretroviral therapy (ART) access with successful outcomes for
      children is expanding in resource-limited countries. The aim of this study was to
      determine treatment responses of children in a routine setting where first-line
      therapy with lopinavir/ritonavir is routinely included for young children.
      METHODS: Outpatient records of children who initiated ART between April 2004 and
      March 2008 at a government clinic in Soweto were reviewed. Children <3 years
      initiated ART with lopinavir/ritonavir and those >= 3 years initiated with
      efavirenz-containing regimens. RESULTS: ART was initiated at a median age of 4.3
      years, 28.6% also received tuberculosis treatment. During 3155 child-years of
      follow-up (median follow-up 17 months), 132 children (6%) died giving a mortality
      rate of 4.2 (95% confidence interval: 3.5, 5.0) deaths per 100 child-years. By 12
      and 24 months, 84% and 96% of children achieved virologic suppression. The
      proportion of children with viral rebound increased from 5.4% to 16.3% at 24 and
      36 months from start of ART. Younger children (receiving lopinavir/ritonavir
      based first-line therapy) with higher viral loads suppressed more slowly and were
      more likely to die. Children who were started on treatment for tuberculosis at
      the time of viral suppression were more likely to have virologic rebound.
      CONCLUSION: Despite good treatment outcomes overall, children with advanced
      disease at ART initiation had poorer outcomes, particularly those <3 years of
      age, most of whom were treated with lopinavir/ritonavir-containing therapy. The
      increasing risk of viral rebound over time for the whole cohort is concerning,
      given currently limited available treatment options for children.

PMID- 21734621
TI  - Efficacy of combined photodynamic therapy and intravitreal bevacizumab injection
      versus photodynamic therapy alone in polypoidal choroidal vasculopathy.
AB  - PURPOSE: To compare the efficacy of combined photodynamic therapy (PDT) and
      optical coherence tomography-guided intravitreal bevacizumab injection versus PDT
      alone for the treatment of polypoidal choroidal vasculopathy. METHODS: The
      medical records of 39 patients with symptomatic polypoidal choroidal vasculopathy
      who received combination therapy with PDT and intravitreal bevacizumab injections
      or PDT monotherapy were retrospectively reviewed. Best-corrected visual acuity,
      number of treatments, and optical coherence tomography and angiographic findings
      were compared between the two patient groups. RESULTS: In the PDT monotherapy
      group (n = 19), the mean number of PDTs was 1.89, whereas in the combined therapy
      group (n = 20), mean 1.30 times of PDT and 2.90 times of intravitreal bevacizumab
      injection were performed during the 12 months of follow-up. The number of PDTs
      was significantly different between the 2 groups (P = 0.032). At 12 months, the
      mean improvement in best-corrected visual acuity was 3.0 lines in the combined
      group and 1.6 lines in the PDT monotherapy group. At 12 months, improved vision
      by >= 3 lines was achieved in 55.0% in the combined therapy group and 36.8% in
      the PDT monotherapy group. CONCLUSION: Combined PDT and bevacizumab therapy
      effectively treated polypoidal choroidal vasculopathy with fewer PDTs compared
      with PDT alone during the 1 year of follow-up. Combined treatment appeared to
      result in better visual acuity, but a larger scale study is required to draw a
      definite conclusion.

PMID- 21734622
TI  - Functional-morphologic correlates in patients with branch retinal vein occlusion
      and macular edema.
AB  - PURPOSE: To investigate the relations among best-corrected visual acuity, retinal
      sensitivity, retinal thickness, and retinal volume in patients with branch
      retinal vein occlusion, and macular edema. METHODS: In 49 consecutive patients
      with branch retinal vein occlusion (mean age, 68.2 +/- 9.9 years; 25 women and 24
      men), macular function was documented by microperimetry and best-corrected visual
      acuity was determined on the logarithm of the minimum angle of resolution scale.
      Retinal thickness and retinal volume were measured by optical coherence
      tomography, and mean retinal sensitivity was calculated for each of nine macular
      subfields on the retinal map obtained by optical coherence tomography. Pearson
      correlation coefficients were calculated and multiple linear regression analysis
      was performed with 7 variables (age, gender, hypertension, hyperlipidemia,
      duration of branch retinal vein occlusion, nonperfused retinal area, and serous
      retinal detachment). RESULTS: On multivariate analysis, best-corrected visual
      acuity was significantly correlated with both retinal thickness and volume in 4
      of 9 retinal subfields (fovea, superior inner, inferior outer, and nasal inner).
      In contrast, retinal sensitivity was correlated with both retinal thickness and
      volume in all 9 retinal subfields. CONCLUSION: Retinal thickness and retinal
      volume are more closely associated with retinal sensitivity than with best
      corrected visual acuity. Measurement of retinal sensitivity may be useful for
      assessing branch retinal vein occlusion patients with macular edema.

PMID- 21734623
TI  - Diagnostic and therapeutic challenges.

PMID- 21734629
TI  - Licocalchone-C extracted from Glycyrrhiza glabra inhibits lipopolysaccharide
      interferon-gamma inflammation by improving antioxidant conditions and regulating
      inducible nitric oxide synthase expression.
AB  - The genus Glycyrrhiza consists of about 30 species, amoung these, G. glabra is
      the source of several phenolic compounds, known as flavonoids, such as
      licoagrodin, licoagrochalcones, licoagroaurone and licochalcone C, kanzonol Y,
      glyinflanin B and glycyrdione A, which have shown various pharmacological
      activities, including antitumor, antiparasitic, antileishmanial, anti-ulcer and
      antioxidative effects. Among these compounds, licochalcone C was isolated but its
      biology has not been fully examined. In our study we reproduced an inflammatory
      state by treating THP-1 (human myelomonocytic leukaemia) cells with pro
      inflammatory stimuli, such as LPS and IFN-gamma and we investigated the possible
      antioxidant activity of licochalcone C at a concentration of 50 MUM. Our results
      show that treatment with licochalcone C attenuates the LPS-IFN-gamma-induced
      inflammatory response by significantly decreasing the expression and activity of
      iNOS via NFkappaB (nuclear factor kappa-B), by influencing extracellular O2-
      production, and by modulating the antioxidant network activity of SOD (superoxide
      dismutase), CAT (catalase) and GPx (glutathione peroxidase) activity. Based on
      these results we hypothesize that Licochalcone C has antioxidant properties since
      it reduces the production of superoxide radicals and consequently reduces the
      activity of iNOS.

PMID- 21734630
TI  - Antioxidant activity of Ixora parviflora in a cell/cell-free system and in UV
      exposed human fibroblasts.
AB  - Polyphenols and flavonoids possess a variety of biological activities including
      antioxidant and anti-tumor activities. Ixora parviflora is a member of the
      flavonoid-rich Rubiaceae family of flowering plants and used as folk medicine in
      India. The aim of this study was to investigate the antioxidant activity of Ixora
      parviflora extract (IPE) in a cell-free system and erythrocytes, and the ability
      of IPE to inhibit reactive oxygen species (ROS) generation in human fibroblasts
      (Hs68) after ultraviolet (UV) exposure. Various in vitro antioxidant assays were
      employed in this study. The extraction yield of IPE was 17.4 +/- 3.9%, the total
      phenolic content of IPE was 26.2 MUg gallic acid equivalent (GAE)/mg leaves dry
      weight and the total flavonoids content was 54.2 +/- 4.4 MUg quercetin equvalent
      (QE)/mg extract. The content of chlorogenic acid was 9.7 +/- 1.2 mg/g extract.
      IPE at 1000 MUg/mL exhibited a reducing capacity of 90.5 +/- 0.6%, a 1,1-diphenyl
      2-picrylhydrazy (DPPH) radical scavenging activity of 96.0 +/- 0.4%, a ferrous
      chelating activity of 72.2 +/- 3.5%, a hydroxyl radical scavenging activity of
      96.8 +/- 1.4%, and a hydrogen peroxide scavenging activity of 99.5 +/- 3.3%. IPE
      at 500 MUg/mL also possessed inhibitory activity against 2,2'-azobis (2
      methylpropionamidine) dihydrochloride (AAPH)-induced hemolysis of erythrocytes
      (89.4 +/- 1.8%) and resulted in a 52.9% reduction in ROS generation in UV-exposed
      fibroblasts. According to our findings, IPE is a potent antioxidant and a
      potential anti-photoaging agent.

PMID- 21734632
TI  - Pentamethylquercetin improves adiponectin expression in differentiated 3T3-L1
      cells via a mechanism that implicates PPARgamma together with TNF-alpha and IL-6.
AB  - Adiponectin is an adipocyte-derived hormone that plays a pivotal role in the
      regulation of lipid and glucose metabolism. Up-regulation of adiponectin
      expression and production has been shown to benefit for metabolic disorders,
      including type 2 diabetes, hyperlipidemia, etc. The present study investigated
      whether the novel polymethoxylated flavonoid pentamethylquercetin (PMQ), a member
      of polymethoxylated flavonoids family which is present in seabuckthorn (Hippophae
      L.) would affect adiponectin production in differentiated 3T3-L1 adipocytes. It
      was found that PMQ increased the adiponectin mRNA and protein expressions in
      adipocytes in time- and concentration-dependent manners. The PPARgamma pathway
      plays a important roles in this effect of PMQ because blockade of PPARgamma by
      GW9662 eliminates the PMQ-induced up-regulation of adiponectin expression.
      Furthermore, significant decreases of mRNA expression and secretion of TNF-alpha
      and IL-6 were also observed in PMQ-treated cells. Taken together, our study
      demonstrated that PMQ up-regulates adiponectin expression via a mechanism that
      implicates PPARgamma together with TNF-alpha and IL-6, suggesting that PMQ might
      be a potential candidate for the treatment of metabolic diseases.

PMID- 21734633
TI  - Drug overdose deaths--Florida, 2003-2009.
AB  - In the United States in 2007, unintentional poisonings were the second leading
      cause of injury death (after motor-vehicle crashes); approximately 93% of all
      unintentional poisoning deaths were caused by drug poisoning, also known as drug
      overdose. From 1990 to 2001 in Florida, the nonsuicidal poisoning death rate
      increased 325%. To characterize recent trends in drug overdose death rates in
      Florida, CDC analyzed data from the Florida Medical Examiners Commission. This
      report summarizes the results of that analysis, which found that, from 2003 to
      2009, the number of annual deaths in which medical examiner testing showed lethal
      concentrations of one or more drugs increased 61.0%, from 1,804 to 2,905, and the
      death rate increased 47.5%, from 10.6 to 15.7 per 100,000 population. During 2003
      2009, death rates increased for all substances except cocaine and heroin. The
      death rate for prescription drugs increased 84.2%, from 7.3 to 13.4 per 100,000
      population. The greatest increase was observed in the death rate from oxycodone
      (264.6%), followed by alprazolam (233.8%) and methadone (79.2%). By 2009, the
      number of deaths involving prescription drugs was four times the number involving
      illicit drugs. These findings indicate the need to strengthen interventions aimed
      at reducing overdose deaths from prescription drugs in Florida. Medical examiner
      records are a timely, population-based source for data regarding overdose deaths
      from specific drugs. The data in this report and subsequent analyses can be used
      to design and measure the effectiveness of interventions.

PMID- 21734634
TI  - Cephalosporin susceptibility among Neisseria gonorrhoeae isolates--United States,
      2000-2010.
AB  - Neisseria gonorrhoeae is a major cause of pelvic inflammatory disease, ectopic
      pregnancy, and infertility, and it can facilitate human immunodeficiency virus
      (HIV) transmission. Emergence of gonococcal resistance to penicillin and
      tetracycline occurred during the 1970s and became widespread during the early
      1980s. More recently, resistance to fluoroquinolones developed. Resistance was
      documented first in Asia, then emerged in the United States in Hawaii followed by
      other western states. It then became prevalent in all other regions of the United
      States. In Hawaii, fluoroquinolone resistance was first noted among
      heterosexuals; however, resistance in the United States initially became
      prevalent among men who have sex with men (MSM) before generalizing to
      heterosexuals. This emergence of resistance led CDC, in 2007, to discontinue
      recommending any fluoroquinolone regimens for the treatment of gonorrhea. CDC now
      recommends dual therapy for gonorrhea with a cephalosporin (ceftriaxone 250 mg)
      plus either azithromycin or doxycycline. This report summarizes trends in
      cephalosporin susceptibility among N. gonorrhoeae isolates in the United States
      during 2000-2010 using data from the Gonococcal Isolate Surveillance Project
      (GISP). During that period, the percentage of isolates with elevated minimum
      inhibitory concentrations (MICs) to cephalosporins (>=0.25 ug/mL for cefixime and
      >=0.125 ug/mL for ceftriaxone) increased from 0.2% in 2000 to 1.4% in 2010 for
      cefixime and from 0.1% in 2000 to 0.3% in 2010 for ceftriaxone. Although
      cephalosporins remain an effective treatment for gonococcal infections, health
      care providers should be vigilant for treatment failure and are requested to
      report its occurrence to state and local health departments. State and local
      public health departments should promote maintenance of laboratory capability to
      culture N. gonorrhoeae to allow testing of isolates for cephalosporin resistance.
      They also should develop enhanced surveillance and response protocols for
      gonorrhea treatment failures and report gonococcal treatment failures to CDC.

PMID- 21734635
TI  - Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2010:
      revised recommendations for the use of contraceptive methods during the
      postpartum period.
AB  - Initiation of contraception during the postpartum period is important to prevent
      unintended pregnancy and short birth intervals, which can lead to negative health
      outcomes for mother and infant. In 2010, CDC published U.S. Medical Eligibility
      Criteria for Contraceptive Use, 2010 (US MEC), providing evidence-based guidance
      for choosing a contraceptive method based on the relative safety of contraceptive
      methods for women with certain characteristics or medical conditions, including
      women who are postpartum. Recently, CDC assessed evidence regarding the safety of
      combined hormonal contraceptive use during the postpartum period. This report
      summarizes that assessment and the resulting updated guidance. These updated
      recommendations state that postpartum women should not use combined hormonal
      contraceptives during the first 21 days after delivery because of the high risk
      for venous thromboembolism (VTE) during this period. During 21-42 days
      postpartum, women without risk factors for VTE generally can initiate combined
      hormonal contraceptives, but women with risk factors for VTE (e.g., previous VTE
      or recent cesarean delivery) generally should not use these methods. After 42
      days postpartum, no restrictions on the use of combined hormonal contraceptives
      based on postpartum status apply.

PMID- 21734636
TI  - Vital signs: Colorectal cancer screening, incidence, and mortality--United
      States, 2002-2010.
AB  - BACKGROUND: Screening lowers colorectal cancer (CRC) incidence and mortality. CRC
      is preventable through the removal of premalignant polyps and is curable if
      diagnosed early. Increased CRC screening and reduced CRC incidence and mortality
      are among the Healthy People 2020 objectives. METHODS: CRC screening data are
      reported using information from 2002-2010 Behavioral Risk Factor Surveillance
      System surveys. State-specific CRC incidence and mortality data were drawn from
      the United States Cancer Statistics. Annual percentage changes (APCs) in
      incidence and death rates from 2003 to 2007 were calculated by state. RESULTS:
      From 2002 to 2010, the percentage of persons aged 50-75 years who were adequately
      screened for colorectal cancer increased from 52.3% to 65.4%. In 2007, CRC
      incidence ranged from 34.3 per 100,000 population in Utah to 56.9 in North
      Dakota; death rates ranged from 12.3 per 100,000 in Utah to 21.1 in the District
      of Columbia (DC). From 2003 to 2007, CRC incidence declined significantly in 35
      states, and mortality declined in 49 states and DC, with APCs ranging from 1.0%
      per year in Alabama to 6.3% per year in Rhode Island. CONCLUSIONS: CRC incidence
      and mortality have declined in recent years throughout the United States, and CRC
      screening has increased. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Continued
      declines in incidence and mortality are expected as past and current public
      health emphasis on the importance of CRC screening become evident with the
      increase in screening. To ensure these gains continue, CRC screening should be
      accessible and used as recommended by all eligible persons in the United States.

PMID- 21734637
TI  - Notes from the field: Botulism caused by consumption of commercially produced
      potato soups stored improperly--Ohio and Georgia, 2011.
AB  - In January and April 2011, CDC provided antitoxin for treatment of two persons
      with toxin type A botulism associated with consumption of potato soup produced by
      two companies. On January 28, 2011, an Ohio resident, aged 29 years, was
      hospitalized after 5 days of progressive dizziness, blurred vision, dysphagia,
      and difficulty breathing. The patient required mechanical ventilation and
      botulism antitoxin. On January 18, he had tasted potato soup from a bulging
      plastic container, noted a bad taste, and discarded the remainder. The soup had
      been purchased on December 7, 2010, from the refrigerated section of a local
      grocer, but it had been kept unrefrigerated for 42 days. He was hospitalized for
      57 days and then was transferred with residual weakness to a rehabilitation
      facility.

PMID- 21734638
TI  - Differential effects of kidney-lung cross-talk during acute kidney injury and
      bacterial pneumonia.
AB  - Acute injuries of the kidney or lung each represent serious, complex clinical
      problems, and their combination drastically decreases patient survival. However,
      detailed understanding of interactions between these two organs is scarce. To
      evaluate this further, we used the folic acid (FA) and myohemoglobinuria models
      of acute kidney injury (AKI) together with Pseudomonas aeruginosa inhalation to
      study kidney-lung cross-talk in mice during acute kidney and lung injury.
      Subgroups of mice received antineutrophil antibody or platelet-depleting serum to
      assess the role of neutrophil and platelets, respectively. AKI by itself did not
      cause clinically relevant acute lung injury. Pneumonia was neutrophil dependent,
      whereas pneumonia-induced AKI was platelet dependent. AKI attenuated pulmonary
      neutrophil recruitment and worsened pneumonia. Mice with AKI had lower oxygen
      saturations and greater bacterial load than mice without. Neutrophils isolated
      from mice with FA-induced AKI also had impaired transmigration and F-actin
      polymerization in vitro. Thus, during acute kidney and pneumonia-induced lung
      injury, clinically relevant kidney-lung interactions are both neutrophil and
      platelet dependent.

PMID- 21734639
TI  - "HUS diary" of a German nephrologist during the current EHEC outbreak in Europe.

PMID- 21734640
TI  - Clinical trial of focal segmental glomerulosclerosis in children and young
      adults.
AB  - This NIH-funded multicenter randomized study of focal segmental
      glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of
      cyclosporine to a combination of oral pulse dexamethasone and mycophenolate
      mofetil in children and adults with steroid-resistant primary FSGS. Of the 192
      patients enrolled, 138 were randomized to cyclosporine (72) or to
      mycophenolate/dexamethasone (66). The primary analysis compared the levels of an
      ordinal variable measuring remission during the first year. The odds ratio (0.59)
      for achieving at least a partial remission with mycophenolate/dexamethasone
      compared to cyclosporine was not significant. Partial or complete remission was
      achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients
      at 12 months. The main secondary outcome, preservation of remission for 26 weeks
      following cessation of treatment, was not significantly different between these
      two therapies. During the entire 78 weeks of study, 8 patients treated with
      cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney
      failure. Thus, our study did not find a difference in rates of proteinuria
      remission following 12 months of cyclosporine compared to
      mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the
      small sample size might have prevented detection of a moderate treatment effect.

PMID- 21734641
TI  - Fibrinogen, acting as a mitogen for tubulointerstitial fibroblasts, promotes
      renal fibrosis.
AB  - Fibrinogen plays an important role in blood coagulation but its function extends
      far beyond blood clotting being involved in inflammation and repair. Besides
      these crucial functions it can also promote tissue fibrosis. To determine whether
      fibrinogen is involved in the development of renal tubulointerstitial fibrosis we
      utilized the profibrotic model of unilateral ureteral obstruction in fibrinogen
      deficient mice. In the heterozygotes, obstruction was associated with a massive
      deposition of intrarenal fibrinogen. Fibrinogen deficiency provided significant
      protection from interstitial damage and tubular disruption, attenuated collagen
      accumulation, and greatly reduced de novo expression of alpha-smooth muscle actin
      in the obstructed kidney. While no differences were found in renal inflammatory
      cell infiltration, fibrinogen deficiency was associated with a significant
      reduction in interstitial cell proliferation, a hallmark of renal fibrosis. In
      vitro, fibrinogen directly stimulated renal fibroblast proliferation in a dose
      dependent manner. This mitogenic effect of fibrinogen was mediated by at least
      three different cell surface receptors on renal fibroblasts: TLR2, TLR4, and ICAM
      1. Thus, our study suggests that fibrinogen promotes renal fibrosis by triggering
      resident fibroblast proliferation.

PMID- 21734642
TI  - Combinatorial depletion analysis to assemble the network architecture of the SAGA
      and ADA chromatin remodeling complexes.
AB  - Despite the availability of several large-scale proteomics studies aiming to
      identify protein interactions on a global scale, little is known about how
      proteins interact and are organized within macromolecular complexes. Here, we
      describe a technique that consists of a combination of biochemistry approaches,
      quantitative proteomics and computational methods using wild-type and deletion
      strains to investigate the organization of proteins within macromolecular protein
      complexes. We applied this technique to determine the organization of two well
      studied complexes, Spt-Ada-Gcn5 histone acetyltransferase (SAGA) and ADA, for
      which no comprehensive high-resolution structures exist. This approach revealed
      that SAGA/ADA is composed of five distinct functional modules, which can persist
      separately. Furthermore, we identified a novel subunit of the ADA complex, termed
      Ahc2, and characterized Sgf29 as an ADA family protein present in all Gcn5
      histone acetyltransferase complexes. Finally, we propose a model for the
      architecture of the SAGA and ADA complexes, which predicts novel functional
      associations within the SAGA complex and provides mechanistic insights into
      phenotypical observations in SAGA mutants.

PMID- 21734643
TI  - Phosphorylation network rewiring by gene duplication.
AB  - Elucidating how complex regulatory networks have assembled during evolution
      requires a detailed understanding of the evolutionary dynamics that follow gene
      duplication events, including changes in post-translational modifications. We
      compared the phosphorylation profiles of paralogous proteins in the budding yeast
      Saccharomyces cerevisiae to that of a species that diverged from the budding
      yeast before the duplication of those genes. We found that 100 million years of
      post-duplication divergence are sufficient for the majority of phosphorylation
      sites to be lost or gained in one paralog or the other, with a strong bias toward
      losses. However, some losses may be partly compensated for by the evolution of
      other phosphosites, as paralogous proteins tend to preserve similar numbers of
      phosphosites over time. We also found that up to 50% of kinase-substrate
      relationships may have been rewired during this period. Our results suggest that
      after gene duplication, proteins tend to subfunctionalize at the level of post
      translational regulation and that even when phosphosites are preserved, there is
      a turnover of the kinases that phosphorylate them.

PMID- 21734644
TI  - Alternative splicing variability: exactly how similar are two identical cells?

PMID- 21734645
TI  - Cell-to-cell variability of alternative RNA splicing.
AB  - Heterogeneity in the expression levels of mammalian genes is large even in clonal
      populations and has phenotypic consequences. Alternative splicing is a
      fundamental aspect of gene expression, yet its contribution to heterogeneity is
      unknown. Here, we use single-molecule imaging to characterize the cell-to-cell
      variability in mRNA isoform ratios for two endogenous genes, CAPRIN1 and MKNK2.
      We show that isoform variability in non-transformed, diploid cells is remarkably
      close to the minimum possible given the stochastic nature of individual splicing
      events, while variability in HeLa cells is considerably higher. Analysis of the
      potential sources of isoform ratio heterogeneity indicates that a difference in
      the control over splicing factor activity is one origin of this increase. Our
      imaging approach also visualizes non-alternatively spliced mRNA and active
      transcription sites, and yields spatial information regarding the relationship
      between splicing and transcription. Together, our work demonstrates that
      mammalian cells minimize fluctuations in mRNA isoform ratios by tightly
      regulating the splicing machinery.

PMID- 21734646
TI  - Fleeting hormone cues get stabilized for plant organogenesis.

PMID- 21734647
TI  - The auxin signalling network translates dynamic input into robust patterning at
      the shoot apex.
AB  - The plant hormone auxin is thought to provide positional information for
      patterning during development. It is still unclear, however, precisely how auxin
      is distributed across tissues and how the hormone is sensed in space and time.
      The control of gene expression in response to auxin involves a complex network of
      over 50 potentially interacting transcriptional activators and repressors, the
      auxin response factors (ARFs) and Aux/IAAs. Here, we perform a large-scale
      analysis of the Aux/IAA-ARF pathway in the shoot apex of Arabidopsis, where
      dynamic auxin-based patterning controls organogenesis. A comprehensive expression
      map and full interactome uncovered an unexpectedly simple distribution and
      structure of this pathway in the shoot apex. A mathematical model of the Aux/IAA
      ARF network predicted a strong buffering capacity along with spatial differences
      in auxin sensitivity. We then tested and confirmed these predictions using a
      novel auxin signalling sensor that reports input into the signalling pathway, in
      conjunction with the published DR5 transcriptional output reporter. Our results
      provide evidence that the auxin signalling network is essential to create robust
      patterns at the shoot apex.

PMID- 21734648
TI  - Microbial laboratory evolution in the era of genome-scale science.
AB  - Laboratory evolution studies provide fundamental biological insight through
      direct observation of the evolution process. They not only enable testing of
      evolutionary theory and principles, but also have applications to metabolic
      engineering and human health. Genome-scale tools are revolutionizing studies of
      laboratory evolution by providing complete determination of the genetic basis of
      adaptation and the changes in the organism's gene expression state. Here, we
      review studies centered on four central themes of laboratory evolution studies:
      (1) the genetic basis of adaptation; (2) the importance of mutations to genes
      that encode regulatory hubs; (3) the view of adaptive evolution as an
      optimization process; and (4) the dynamics with which laboratory populations
      evolve.

PMID- 21734649
TI  - The characteristic long-term upregulation of hippocampal NF-kappaB complex in
      PTSD-like behavioral stress response is normalized by high-dose corticosterone
      and pyrrolidine dithiocarbamate administered immediately after exposure.
AB  - Nuclear factor-kappaB (NF-kappaB) is a ubiquitously expressed transcription
      factor for genes involved in cell survival, differentiation, inflammation, and
      growth. This study examined the role of NF-kappaB pathway in stress-induced PTSD
      like behavioral response patterns in rats. Immunohistochemical technique was used
      to detect the expression of the NF-kappaB p50 and p65 subunits, I-kappaBalpha,
      p38, and phospho-p38 in the hippocampal subregions at 7 days after exposure to
      predator scent stress. Expression of p65 nuclear translocation was quantified by
      western blot as the level of NF-kappaB activation. The effects of
      intraperitoneally administered corticosterone or a selective NF-kappaB inhibitor
      (pyrrolidine dithiocarbamate (PDTC)) at 1 h post exposure on behavioral tests
      (elevated plus-maze and acoustic startle response) were evaluated 7 days later.
      Hippocampal expressions of those genes were subsequently evaluated. All data were
      analyzed in relation to individual behavior patterns. Extreme behavioral
      responder animals displayed significant upregulation of p50 and p65 with
      concomitant downregulation of I-kappaBalpha, p38, and phospho-p38 levels in
      hippocampal structures compared with minimal behavioral responders and controls.
      Immediate post-exposure treatment with high-dose corticosterone and PDTC
      significantly reduced prevalence rates of extreme responders and normalized the
      expression of those genes. Stress-induced upregulation of NF-kappaB complex in
      the hippocampus may contribute to the imbalance between what are normally
      precisely orchestrated and highly coordinated physiological and behavioral
      processes, thus associating it with stress-related disorders.

PMID- 21734650
TI  - Activation of MU-opioid receptors in the dorsal striatum is necessary for adult
      social attachment in monogamous prairie voles.
AB  - Despite significant evidence that opioids are involved in attachment by mediating
      social reward and motivation, the role of opioids in the formation of adult
      social attachments has not been explored. We used the socially monogamous prairie
      vole (Microtus ochrogaster) to explore the role of endogenous opioids in social
      bonding by examining partner preference formation in female prairie voles. We
      hypothesized that MU-opioid receptors (MORs) in the striatum have a critical role
      in partner preference formation. We therefore predicted that peripheral
      administration of an opioid receptor antagonist would inhibit partner preference
      formation, and more specifically, that MU-opioid selective receptor blockade
      within the striatum would inhibit partner preference formation. To test our
      hypotheses, we first administered the non-selective opioid antagonist naltrexone
      peripherally to females during an 18-h cohabitation with a male and later tested
      the female with a partner preference test (PPT). Females showed a dose schedule
      dependent decrease in partner preference in the PPT, with females in the
      continuous dose group displaying stranger preferences. Next, we administered
      microinjections of the MOR selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen
      Thr-NH2 (CTAP) into either the nucleus accumbens shell (NAS) or the caudate
      putamen (CP) immediately before a 24-h cohabitation with a male, and later tested
      the female with a PPT. Females receiving CTAP into the CP, but not the NAS,
      showed no preference in the PPT, indicating an inhibition of partner preference
      formation. We show here for the first time that MORs modulate partner preference
      formation in female prairie voles by acting in the CP.

PMID- 21734651
TI  - Activation of group II metabotropic glutamate receptors inhibits the
      discriminative stimulus effects of alcohol via selective activity within the
      amygdala.
AB  - Metabotropic glutamate receptor subtypes (mGlu2/3) regulate a variety of alcohol
      associated behaviors, including alcohol reinforcement, and relapse-like behavior.
      To date, the role of mGlu2/3 receptors in modulating the discriminative stimulus
      effects of alcohol has not been examined. Given that the discriminative stimulus
      effects of drugs are determinants of abuse liability and can influence drug
      seeking, we examined the contributions of mGlu2/3 receptors in modulating the
      discriminative stimulus effects of alcohol. In male Long-Evans rats trained to
      discriminate between alcohol (1 g/kg, IG) and water, the mGlu2/3 agonist LY379268
      (0.3-10 mg/kg) did not produce alcohol-like stimulus effects. However,
      pretreatment with LY379268 (1 and 3 mg/kg; in combination with alcohol) inhibited
      the stimulus effects of alcohol (1 g/kg). Systemic LY379268 (3 mg/kg, i.p.) was
      associated with increases in neuronal activity within the amygdala, but not the
      nucleus accumbens, as assessed by c-Fos immunoreactivity. Intra-amygdala
      activation of mGlu2/3 receptors by LY379268 (6 MUg) inhibited the discriminative
      stimulus effects of alcohol, without altering response rate. In contrast, intra
      accumbens LY379268 (3 MUg) profoundly reduced response rate; however, at lower
      LY379268 doses (0.3, 1 MUg), the discriminative stimulus effects of alcohol and
      response rate were not altered. These data suggest that amygdala mGlu2/3
      receptors have a functional role in modulating the discriminative stimulus
      properties of alcohol and demonstrate differential motor sensitivity to
      activation of mGlu2/3 receptors in the amygdala and the accumbens. Understanding
      the neuronal mechanisms that underlie the discriminative stimulus effects of
      alcohol may prove to be important for future development of pharmacotherapies for
      treating alcoholism.

PMID- 21734652
TI  - Increasing CREB function in the CA1 region of dorsal hippocampus rescues the
      spatial memory deficits in a mouse model of Alzheimer's disease.
AB  - The principal defining feature of Alzheimer's disease (AD) is memory impairment.
      As the transcription factor CREB (cAMP/Ca(2+) responsive element-binding protein)
      is critical for memory formation across species, we investigated the role of CREB
      in a mouse model of AD. We found that TgCRND8 mice exhibit a profound impairment
      in the ability to form a spatial memory, a process that critically relies on the
      dorsal hippocampus. Perhaps contributing to this memory deficit, we observed
      additional deficits in the dorsal hippocampus of TgCRND8 mice in terms of (1)
      biochemistry (decreased CREB activation in the CA1 region), (2) neuronal
      structure (decreased spine density and dendritic complexity of CA1 pyramidal
      neurons), and (3) neuronal network activity (decreased arc mRNA levels following
      behavioral training). Locally and acutely increasing CREB function in the CA1
      region of dorsal hippocampus of TgCRND8 mice was sufficient to restore function
      in each of these key domains (biochemistry, neuronal structure, network activity,
      and most importantly, memory formation). The rescue produced by increasing CREB
      was specific both anatomically and behaviorally and independent of plaque load or
      Abeta levels. Interestingly, humans with AD show poor spatial memory/navigation
      and AD brains have disrupted (1) CREB activation, and (2) spine density and
      dendritic complexity in hippocampal CA1 pyramidal neurons. These parallel
      findings not only confirm that TgCRND8 mice accurately model key aspects of human
      AD, but furthermore, suggest the intriguing possibility that targeting CREB may
      be a useful therapeutic strategy in treating humans with AD.

PMID- 21734653
TI  - Prevention of vaginal SHIV transmission in macaques by a live recombinant
      Lactobacillus.
AB  - Most human immunodeficiency virus (HIV) transmissions in women occur through the
      cervicovaginal mucosa, which is coated by a bacterial biofilm including
      Lactobacillus. This commensal bacterium has a role in maintaining a healthy
      mucosa and can be genetically engineered to produce antiviral peptides. Here, we
      report a 63% reduction in transmission of a chimeric simian/HIV (SHIV(SF162P3))
      after repeated vaginal challenges of macaques treated with Lactobacillus jensenii
      expressing the HIV-1 entry inhibitor cyanovirin-N. Furthermore, peak viral loads
      in colonized macaques with breakthrough infection were reduced sixfold.
      Colonization and prolonged antiviral protein secretion by the genetically
      engineered lactobacilli did not cause any increase in proinflammatory markers.
      These findings lay the foundation for an accessible and durable approach to
      reduce heterosexual transmission of HIV in women, which is coitally independent,
      inexpensive, and enhances the natural protective effects of the vaginal
      microflora.

PMID- 21734654
TI  - New therapeutic approaches to antibody-mediated rejection in renal
      transplantation.

PMID- 21734656
TI  - Legionella pneumophila SidD is a deAMPylase that modifies Rab1.
AB  - Legionella pneumophila actively modulates host vesicle trafficking pathways to
      facilitate its intracellular replication with effectors translocated by the
      Dot/Icm type IV secretion system (T4SS). The SidM/DrrA protein functions by
      locking the small GTPase Rab1 into an active form by its guanine nucleotide
      exchange factor (GEF) and AMPylation activity. Here we demonstrate that the L.
      pneumophila protein SidD preferably deAMPylates Rab1. We found that the
      deAMPylation activity of SidD could suppress the toxicity of SidM to yeast and is
      required to release Rab1 from bacterial phagosomes efficiently. A molecular
      mechanism for the temporal control of Rab1 activity in different phases of L.
      pneumophila infection is thus established. These observations indicate that
      AMPylation-mediated signal transduction is a reversible process regulated by
      specific enzymes.

PMID- 21734657
TI  - Sideband cooling of micromechanical motion to the quantum ground state.
AB  - The advent of laser cooling techniques revolutionized the study of many atomic
      scale systems, fuelling progress towards quantum computing with trapped ions and
      generating new states of matter with Bose-Einstein condensates. Analogous cooling
      techniques can provide a general and flexible method of preparing macroscopic
      objects in their motional ground state. Cavity optomechanical or
      electromechanical systems achieve sideband cooling through the strong interaction
      between light and motion. However, entering the quantum regime--in which a system
      has less than a single quantum of motion--has been difficult because sideband
      cooling has not sufficiently overwhelmed the coupling of low-frequency mechanical
      systems to their hot environments. Here we demonstrate sideband cooling of an
      approximately 10-MHz micromechanical oscillator to the quantum ground state. This
      achievement required a large electromechanical interaction, which was obtained by
      embedding a micromechanical membrane into a superconducting microwave resonant
      circuit. To verify the cooling of the membrane motion to a phonon occupation of
      0.34 +/- 0.05 phonons, we perform a near-Heisenberg-limited position measurement
      within (5.1 +/- 0.4)h/2pi, where h is Planck's constant. Furthermore, our device
      exhibits strong coupling, allowing coherent exchange of microwave photons and
      mechanical phonons. Simultaneously achieving strong coupling, ground state
      preparation and efficient measurement sets the stage for rapid advances in the
      control and detection of non-classical states of motion, possibly even testing
      quantum theory itself in the unexplored region of larger size and mass. Because
      mechanical oscillators can couple to light of any frequency, they could also
      serve as a unique intermediary for transferring quantum information between
      microwave and optical domains.

PMID- 21734658
TI  - Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its
      substrate TBP.
AB  - Swi2/Snf2-type ATPases regulate genome-associated processes such as
      transcription, replication and repair by catalysing the disruption, assembly or
      remodelling of nucleosomes or other protein-DNA complexes. It has been suggested
      that ATP-driven motor activity along DNA disrupts target protein-DNA interactions
      in the remodelling reaction. However, the complex and highly specific remodelling
      reactions are poorly understood, mostly because of a lack of high-resolution
      structural information about how remodellers bind to their substrate proteins.
      Mot1 (modifier of transcription 1 in Saccharomyces cerevisiae, denoted BTAF1 in
      humans) is a Swi2/Snf2 enzyme that specifically displaces the TATA box binding
      protein (TBP) from the promoter DNA and regulates transcription globally by
      generating a highly dynamic TBP pool in the cell. As a Swi2/Snf2 enzyme that
      functions as a single polypeptide and interacts with a relatively simple
      substrate, Mot1 offers an ideal system from which to gain a better understanding
      of this important enzyme family. To reveal how Mot1 specifically disrupts TBP-DNA
      complexes, we combined crystal and electron microscopy structures of Mot1-TBP
      from Encephalitozoon cuniculi with biochemical studies. Here we show that Mot1
      wraps around TBP and seems to act like a bottle opener: a spring-like array of 16
      HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase
      TOR) repeats grips the DNA-distal side of TBP via loop insertions, and the
      Swi2/Snf2 domain binds to upstream DNA, positioned to weaken the TBP-DNA
      interaction by DNA translocation. A 'latch' subsequently blocks the DNA-binding
      groove of TBP, acting as a chaperone to prevent DNA re-association and ensure
      efficient promoter clearance. This work shows how a remodelling enzyme can
      combine both motor and chaperone activities to achieve functional specificity
      using a conserved Swi2/Snf2 translocase.

PMID- 21734659
TI  - Excess digestive capacity in predators reflects a life of feast and famine.
AB  - A central challenge for predators is achieving positive energy balance when prey
      are spatially and temporally heterogeneous. Ecological heterogeneity produces
      evolutionary trade-offs in the physiological design of predators; this is because
      the ability to capitalize on pulses of food abundance requires high capacity for
      food-processing, yet maintaining such capacity imposes energetic costs that are
      taxing during periods of food scarcity. Recent advances in physiology show that
      when variation in foraging opportunities is predictable, animals may adjust
      energetic trade-offs by rapidly modulating their digestive system to track
      variation in foraging opportunities. However, it is increasingly recognized that
      foraging opportunities for animals are unpredictable, which should favour animals
      that maintain a capacity for food-processing that exceeds average levels of
      consumption (loads). Despite this basic principle of quantitative evolutionary
      design, estimates of digestive load:capacity ratios in wild animals are virtually
      non-existent. Here we provide an extensive assessment of load:capacity ratios for
      the digestive systems of predators in the wild, compiling 639 estimates across 38
      species of fish. We found that piscine predators typically maintain the
      physiological capacity to feed at daily rates 2-3 times higher than what they
      experience on average. A numerical simulation of the trade-off between food
      processing capacity and metabolic cost suggests that the observed level of
      physiological opportunism is profitable only if predator-prey encounters, and
      thus predator energy budgets, are far more variable in nature than currently
      assumed.

PMID- 21734660
TI  - Initial radiation of jaws demonstrated stability despite faunal and environmental
      change.
AB  - More than 99 per cent of the roughly 58,000 living vertebrate species have jaws.
      This major clade, whose members are collectively known as gnathostomes ('jawed
      mouths'), made its earliest definitive appearance in the Silurian period, 444-416
      million years (Myr) ago, with both the origin of the modern (crown-group)
      radiation and the presumptive invasion of land occurring by the end of the
      Devonian period (359 Myr ago). These events coincided with a major faunal shift
      that remains apparent today: the transition from Silurian ecosystems dominated by
      jawless fishes (agnathans) to younger assemblages composed almost exclusively of
      gnathostomes. This pattern has inspired several qualitative descriptions of the
      trophic radiation and ecological ascendance of the earliest jawed vertebrates.
      Here we present a quantitative analysis of functional variation in early
      gnathostome mandibular elements, placing constraints on our understanding of
      evolutionary patterns during this critical interval. We document an initial
      increase in functional disparity in the Silurian that stabilized by the first
      stage of the Devonian, before the occurrence of an Emsian (~400 Myr ago)
      oxygenation event implicated in the trophic radiation of vertebrates. Subsequent
      taxonomic diversification during the Devonian did not result in increased
      functional variation; instead, new taxa revisited and elaborated on established
      mandibular designs. Devonian functional space is dominated by lobe-finned fishes
      and 'placoderms'; high disparity within the latter implies considerable trophic
      innovation among jaw-bearing stem gnathostomes. By contrast, the major groups of
      living vertebrates--ray-finned fishes and tetrapods--show surprisingly
      conservative mandibular morphologies with little indication of functional
      diversification or innovation. Devonian gnathostomes reached a point where they
      ceased to accrue further mandibular functional disparity before becoming
      taxonomic dominants relative to 'ostracoderm'-grade jawless fishes, providing a
      new perspective on classic adaptive hypotheses concerning this fundamental shift
      in vertebrate biodiversity.

PMID- 21734661
TI  - A strong ferroelectric ferromagnet created by means of spin-lattice coupling.

PMID- 21734662
TI  - Activation energy.

PMID- 21734663
TI  - Taken for a ride.

PMID- 21734664
TI  - Up and away.

PMID- 21734665
TI  - Fishery reform slips through the net.

PMID- 21734677
TI  - Greek crisis spurs research reforms.

PMID- 21734678
TI  - Europe lines up hefty science-funding hike.

PMID- 21734679
TI  - NASA faces dearth of mission leaders.

PMID- 21734680
TI  - Spain's ship comes in.

PMID- 21734681
TI  - NIH cancer chief wants more with less: by Meredith Wadman.

PMID- 21734682
TI  - Mosquitoes score in chemical war.

PMID- 21734683
TI  - Misconduct at the DOE: investigation closed.

PMID- 21734684
TI  - Nutrition advice: the vitamin D-lemma.

PMID- 21734685
TI  - Grand challenges in global mental health.

PMID- 21734686
TI  - Don't define nanomaterials.

PMID- 21734688
TI  - Non-natives: put biodiversity at risk.

PMID- 21734689
TI  - Non-natives: 141 scientists object.

PMID- 21734690
TI  - Non-natives: four risk factors.

PMID- 21734691
TI  - Non-natives: plusses of invasion ecology.

PMID- 21734693
TI  - UK cancer genetics gets personal.

PMID- 21734694
TI  - Nuclear winter was and is debatable.

PMID- 21734695
TI  - All-male line-up yet again.

PMID- 21734697
TI  - Earth science: plate motion and mantle plumes.

PMID- 21734698
TI  - Structural biology: a platform for copper pumps.

PMID- 21734699
TI  - Cancer: when antioxidants are bad.

PMID- 21734700
TI  - Saturn: storm-clouds brooding on towering heights.

PMID- 21734701
TI  - Metabolism: alcohol, DNA and disease.

PMID- 21734702
TI  - Indian and African plate motions driven by the push force of the Reunion plume
      head.
AB  - Mantle plumes are thought to play an important part in the Earth's tectonics, yet
      it has been difficult to isolate the effect that plumes have on plate motions.
      Here we analyse the plate motions involved in two apparently disparate events-
      the unusually rapid motion of India between 67 and 52 million years ago and a
      contemporaneous, transitory slowing of Africa's motion--and show that the events
      are coupled, with the common element being the position of the Indian and African
      plates relative to the location of the Reunion plume head. The synchroneity of
      these events suggests that they were both driven by the force of the Reunion
      plume head. The recognition of this plume force has substantial tectonic
      implications: the speed-up and slowdown of India, the possible cessation of
      convergence between Africa and Eurasia in the Palaeocene epoch and the enigmatic
      bends of the fracture zones on the Southwest Indian Ridge can all be attributed
      to the Reunion plume.

PMID- 21734703
TI  - Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice.
AB  - Reactive aldehydes are common carcinogens. They are also by-products of several
      metabolic pathways and, without enzymatic catabolism, may accumulate and cause
      DNA damage. Ethanol, which is metabolised to acetaldehyde, is both carcinogenic
      and teratogenic in humans. Here we find that the Fanconi anaemia DNA repair
      pathway counteracts acetaldehyde-induced genotoxicity in mice. Our results show
      that the acetaldehyde-catabolising enzyme Aldh2 is essential for the development
      of Fancd2(-/-) embryos. Nevertheless, acetaldehyde-catabolism-competent mothers
      (Aldh2(+/-)) can support the development of double-mutant (Aldh2(-/-)Fancd2(-/-))
      mice. However, these embryos are unusually sensitive to ethanol exposure in
      utero, and ethanol consumption by postnatal double-deficient mice rapidly
      precipitates bone marrow failure. Lastly, Aldh2(-/-)Fancd2(-/-) mice
      spontaneously develop acute leukaemia. Acetaldehyde-mediated DNA damage may
      critically contribute to the genesis of fetal alcohol syndrome in fetuses, as
      well as to abnormal development, haematopoietic failure and cancer predisposition
      in Fanconi anaemia patients.

PMID- 21734704
TI  - Deep winds beneath Saturn's upper clouds from a seasonal long-lived planetary
      scale storm.
AB  - Convective storms occur regularly in Saturn's atmosphere. Huge storms known as
      Great White Spots, which are ten times larger than the regular storms, are rarer
      and occur about once per Saturnian year (29.5 Earth years). Current models
      propose that the outbreak of a Great White Spot is due to moist convection
      induced by water. However, the generation of the global disturbance and its
      effect on Saturn's permanent winds have hitherto been unconstrained by data,
      because there was insufficient spatial resolution and temporal sampling to infer
      the dynamics of Saturn's weather layer (the layer in the troposphere where the
      cloud forms). Theoretically, it has been suggested that this phenomenon is
      seasonally controlled. Here we report observations of a storm at northern
      latitudes in the peak of a weak westward jet during the beginning of northern
      springtime, in accord with the seasonal cycle but earlier than expected. The
      storm head moved faster than the jet, was active during the two-month observation
      period, and triggered a planetary-scale disturbance that circled Saturn but did
      not significantly alter the ambient zonal winds. Numerical simulations of the
      phenomenon show that, as on Jupiter, Saturn's winds extend without decay deep
      down into the weather layer, at least to the water-cloud base at pressures of 10
      12 bar, which is much deeper than solar radiation penetrates.

PMID- 21734705
TI  - A giant thunderstorm on Saturn.
AB  - Lightning discharges in Saturn's atmosphere emit radio waves with intensities
      about 10,000 times stronger than those of their terrestrial counterparts. These
      radio waves are the characteristic features of lightning from thunderstorms on
      Saturn, which last for days to months. Convective storms about 2,000 kilometres
      in size have been observed in recent years at planetocentric latitude 35 degrees 
      south (corresponding to a planetographic latitude of 41 degrees  south). Here we
      report observations of a giant thunderstorm at planetocentric latitude 35 degrees
      north that reached a latitudinal extension of 10,000 kilometres-comparable in
      size to a 'Great White Spot'-about three weeks after it started in early December
      2010. The visible plume consists of high-altitude clouds that overshoot the
      outermost ammonia cloud layer owing to strong vertical convection, as is typical
      for thunderstorms. The flash rates of this storm are about an order of magnitude
      higher than previous ones, and peak rates larger than ten per second were
      recorded. This main storm developed an elongated eastward tail with additional
      but weaker storm cells that wrapped around the whole planet by February 2011.
      Unlike storms on Earth, the total power of this storm is comparable to Saturn's
      total emitted power. The appearance of such storms in the northern hemisphere
      could be related to the change of seasons, given that Saturn experienced vernal
      equinox in August 2009.

PMID- 21734706
TI  - Attosecond control of electrons emitted from a nanoscale metal tip.
AB  - Attosecond science is based on steering electrons with the electric field of well
      controlled femtosecond laser pulses. It has led to the generation of extreme
      ultraviolet pulses with a duration of less than 100 attoseconds (ref. 3; 1 as =
      10(-18) s), to the measurement of intramolecular dynamics (by diffraction of an
      electron taken from the molecule under scrutiny) and to ultrafast electron
      holography. All these effects have been observed with atoms or molecules in the
      gas phase. Electrons liberated from solids by few-cycle laser pulses are also
      predicted to show a strong light-phase sensitivity, but only very small effects
      have been observed. Here we report that the spectra of electrons undergoing
      photoemission from a nanometre-scale tungsten tip show a dependence on the
      carrier-envelope phase of the laser, with a current modulation of up to 100 per
      cent. Depending on the carrier-envelope phase, electrons are emitted either from
      a single sub-500-attosecond interval of the 6-femtosecond laser pulse, or from
      two such intervals; the latter case leads to spectral interference. We also show
      that coherent elastic re-scattering of liberated electrons takes place at the
      metal surface. Owing to field enhancement at the tip, a simple laser oscillator
      reaches the peak electric field strengths required for attosecond experiments at
      100-megahertz repetition rates, rendering complex amplified laser systems
      dispensable. Practically, this work represents a simple, extremely sensitive
      carrier-envelope phase sensor, which could be shrunk in volume to about one cubic
      centimetre. Our results indicate that the attosecond techniques developed with
      (and for) atoms and molecules can also be used with solids. In particular, we
      foresee subfemtosecond, subnanometre probing of collective electron dynamics
      (such as plasmon polaritons) in solid-state systems ranging in scale from
      mesoscopic solids to clusters and to single protruding atoms.

PMID- 21734707
TI  - Oncogene-induced Nrf2 transcription promotes ROS detoxification and
      tumorigenesis.
AB  - Reactive oxygen species (ROS) are mutagenic and may thereby promote cancer.
      Normally, ROS levels are tightly controlled by an inducible antioxidant program
      that responds to cellular stressors and is predominantly regulated by the
      transcription factor Nrf2 (also known as Nfe2l2) and its repressor protein Keap1
      (refs 2-5). In contrast to the acute physiological regulation of Nrf2, in
      neoplasia there is evidence for increased basal activation of Nrf2. Indeed,
      somatic mutations that disrupt the Nrf2-Keap1 interaction to stabilize Nrf2 and
      increase the constitutive transcription of Nrf2 target genes were recently
      identified, indicating that enhanced ROS detoxification and additional Nrf2
      functions may in fact be pro-tumorigenic. Here, we investigated ROS metabolism in
      primary murine cells following the expression of endogenous oncogenic alleles of
      Kras, Braf and Myc, and found that ROS are actively suppressed by these
      oncogenes. K-Ras(G12D), B-Raf(V619E) and Myc(ERT2) each increased the
      transcription of Nrf2 to stably elevate the basal Nrf2 antioxidant program and
      thereby lower intracellular ROS and confer a more reduced intracellular
      environment. Oncogene-directed increased expression of Nrf2 is a new mechanism
      for the activation of the Nrf2 antioxidant program, and is evident in primary
      cells and tissues of mice expressing K-Ras(G12D) and B-Raf(V619E), and in human
      pancreatic cancer. Furthermore, genetic targeting of the Nrf2 pathway impairs K
      Ras(G12D)-induced proliferation and tumorigenesis in vivo. Thus, the Nrf2
      antioxidant and cellular detoxification program represents a previously
      unappreciated mediator of oncogenesis.

PMID- 21734708
TI  - The ribosome uses two active mechanisms to unwind messenger RNA during
      translation.
AB  - The ribosome translates the genetic information encoded in messenger RNA into
      protein. Folded structures in the coding region of an mRNA represent a kinetic
      barrier that lowers the peptide elongation rate, as the ribosome must disrupt
      structures it encounters in the mRNA at its entry site to allow translocation to
      the next codon. Such structures are exploited by the cell to create diverse
      strategies for translation regulation, such as programmed frameshifting, the
      modulation of protein expression levels, ribosome localization and co
      translational protein folding. Although strand separation activity is inherent to
      the ribosome, requiring no exogenous helicases, its mechanism is still unknown.
      Here, using a single-molecule optical tweezers assay on mRNA hairpins, we find
      that the translation rate of identical codons at the decoding centre is greatly
      influenced by the GC content of folded structures at the mRNA entry site.
      Furthermore, force applied to the ends of the hairpin to favour its unfolding
      significantly speeds translation. Quantitative analysis of the force dependence
      of its helicase activity reveals that the ribosome, unlike previously studied
      helicases, uses two distinct active mechanisms to unwind mRNA structure: it
      destabilizes the helical junction at the mRNA entry site by biasing its thermal
      fluctuations towards the open state, increasing the probability of the ribosome
      translocating unhindered; and it mechanically pulls apart the mRNA single strands
      of the closed junction during the conformational changes that accompany ribosome
      translocation. The second of these mechanisms ensures a minimal basal rate of
      translation in the cell; specialized, mechanically stable structures are required
      to stall the ribosome temporarily. Our results establish a quantitative
      mechanical basis for understanding the mechanism of regulation of the elongation
      rate of translation by structured mRNAs.

PMID- 21734709
TI  - Animal models: inside the minds of mice and men.

PMID- 21734712
TI  - A polymorphism of the POLG2 gene is genetically associated with the invasiveness
      of urinary bladder cancer in Japanese males.
AB  - Urinary bladder cancer (UBC) is a common cancer with male predominance.
      Pathologically it is classified into two distinct tumor entities related to the
      risk of patients. The low-grade tumors with relatively well-differentiated tumor
      histology (G1 and G2) at stage Ta are non-invasive and pose a minimal risk,
      whereas high-grade tumors (G2 and G3) with stages T1 to T4 are aggressive with
      invasion, and therefore, pose a serious risk for the patients. DNA repair and
      metabolic process genes may have major roles in cancer progression and
      development. To identify genes associated with invasiveness of UBC, we have
      extensively genotyped 802 single nucleotide polymorphisms in 114 genes related to
      DNA repair mechanisms and metabolic processes. A genetic association study was
      performed between non-invasive (G1 and G2 with Ta) and invasive (G2 and G3 with
      T1 to T4) groups of Japanese UBC patients. We found that rs17650301 in POLG2
      showed marked difference in genotype distribution between the two groups in males
      (P=6.93 * 10(-4)), which was further confirmed in an independent sample set
      (overall P=1.67 * 10(-4)). We also found by an in silico analysis that the risk
      allele of rs17650301 increased the transcription of POLG2. In conclusion,
      rs17650301 is a good candidate marker for UBC invasiveness in Japanese males.

PMID- 21734713
TI  - A new case of keratin 14 functional knockout causes severe recessive EBS and
      questions the haploinsufficiency model of Naegeli-Franceschetti-Jadassohn
      syndrome.

PMID- 21734714
TI  - Clinical and pharmacogenetic influences on response to hydroxychloroquine in
      discoid lupus erythematosus: a retrospective cohort study.
AB  - The recommended systemic therapy of choice for discoid lupus erythematosus (DLE)
      is the 4-aminoquinolone antimalarial hydroxychloroquine. There is limited
      published information on the likelihood of clinical response and, in particular,
      what factors influence outcome. We conducted a multicenter observational and
      pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine.
      The primary outcome was clinical response to hydroxychloroquine. We investigated
      the effects of disease attributes and metabolizing cytochrome P450 (CYP)
      polymorphisms on clinical outcome. Although the majority of patients responded to
      hydroxychloroquine, a significant proportion (39%) either failed to respond or
      was intolerant of the drug. Cigarette smoking and CYP genotype did not have any
      significant influence on response to hydroxychloroquine. Moreover, multivariate
      analysis indicated that disseminated disease (odds ratio (OR): 0.21; 95%
      confidence interval (CI): 0.08-0.52; P<0.001) and concomitant systemic lupus
      erythematosus (SLE; OR: 0.06; 95% CI: 0.01-0.49; P = 0.009) were significantly
      associated with lack of response to hydroxychloroquine. These findings suggest
      that baseline lupus severity and SLE are predictors of response to
      hydroxychloroquine. A prospective study is now required to further investigate
      the relationship between disease activity and response to hydroxychloroquine.
      This will have the potential to further inform the clinical management of this
      disfiguring photosensitive disease.

PMID- 21734715
TI  - Skin as a peripheral lymphoid organ: revisiting the concept of skin-associated
      lymphoid tissues.
AB  - Antigen presentation to T cells is essential for the induction of adaptive
      immunity. This event takes place not solely in the lymph node (LN) but also in
      the skin. Recent in vivo trafficking studies using Kaede-transgenic mice reveal
      that skin-homing effector memory T cells alter their effector function and homing
      ability by transitioning to a central memory T cell-like phenotype through
      antigen recognition that occurs in the skin. In addition, these cells travel back
      and forth between the skin and draining LNs. These studies are evocative of the
      classic concept of skin-associated lymphoid tissues and underscore the critical
      role of skin as a peripheral lymphoid organ.

PMID- 21734716
TI  - Selective loss of wild-type p16(INK4a) expression in human nevi.

PMID- 21734717
TI  - Digenic inheritance of mutations in the coproporphyrinogen oxidase and
      protoporphyrinogen oxidase genes in a unique type of porphyria.
AB  - The simultaneous dysfunction of two enzymes within the heme biosynthetic pathway
      in a single patient is rare. Not more than 15 cases have been reported. A woman
      with a transient episode of severe photosensitivity showed a biochemical
      porphyrin profile suggestive of hereditary coproporphyria (HCP), whereas some of
      her relatives had a profile that was suggestive of variegate porphyria (VP). HCP
      and VP result from a partial enzymatic deficiency of coproporphyrinogen oxidase
      (CPOX) and protoporphyrinogen oxidase (PPOX), respectively. DNA analysis in the
      index patient revealed mutations in both the CPOX and PPOX genes, designated as
      c.557-15C>G and c.1289dupT, respectively. The CPOX mutation leads to a cryptic
      splice site resulting in retention of 14 nucleotides from intron 1 in the mRNA
      transcript. Both mutations encode null alleles and were associated with nonsense
      mediated mRNA decay. Given the digenic inheritance of these null mutations,
      coupled with the fact that both HCP and VP can manifest with life-threatening
      acute neurovisceral attacks, the unusual aspect of this case is a relatively mild
      clinical phenotype restricted to dermal photosensitivity.

PMID- 21734719
TI  - Interferon-inducible Ifi202b gene in (NZB * NZW)F(1) lupus-prone mice.

PMID- 21734720
TI  - The sympathetic nervous system and blood pressure in humans: implications for
      hypertension.
AB  - A neurogenic component to primary hypertension (hypertension) is now well
      established. Along with raised vasomotor tone and increased cardiac output, the
      chronic activation of the sympathetic nervous system in hypertension has a
      diverse range of pathophysiological consequences independent of any increase in
      blood pressure. This review provides a perspective on the actions and
      interactions of angiotensin II, inflammation and vascular dysfunction/brain
      hypoperfusion in the pathogenesis and progression of neurogenic hypertension. The
      optimisation of current treatment strategies and the exciting recent developments
      in the therapeutic targeting of the sympathetic nervous system to control
      hypertension (for example, catheter-based renal denervation and carotid
      baroreceptor stimulation) will be outlined.

PMID- 21734721
TI  - Effect of 12 weeks of resistance exercise on post-exercise hypotension in stage 1
      hypertensive individuals.
AB  - Post-exercise hypotension (PEH), the reduction of blood pressure (BP) after a
      single bout of exercise, is of great clinical relevance. As the magnitude of this
      phenomenon seems to be dependent on pre-exercise BP values and chronic exercise
      training in hypertensive individuals leads to BP reduction; PEH could be
      attenuated in this context. Therefore, the aim of the present study was to
      investigate whether PEH remains constant after resistance exercise training.
      Fifteen hypertensive individuals (46 +/- 8 years; 88 +/- 16 kg; 30 +/- 6% body
      fat; 150 +/- 13/93 +/- 5 mm Hg systolic/diastolic BP, SBP/DBP) were withdrawn
      from medication and performed 12 weeks of moderate-intensity resistance training.
      Parameters of cardiovascular function were evaluated before and after the
      training period. Before the training program, hypertensive volunteers showed
      significant PEH. After an acute moderate-intensity resistance exercise session
      with three sets of 12 repetitions (60% of one repetition maximum) and a total of
      seven exercises, BP was reduced post-exercise (45-60 min) by an average of
      aproximately -22 mm Hg for SBP, -8 mm Hg for DBP and -13 mm Hg for mean arterial
      pressure (P<0.05). However, this acute hypotensive effect did not occur after the
      12 weeks of training (P>0.05). In conclusion, our data demonstrate that PEH,
      following an acute exercise session, can indeed be attenuated after 12 weeks of
      training in hypertensive stage 1 patients not using antihypertensive medication.

PMID- 21734722
TI  - Cancer biology and NuRD: a multifaceted chromatin remodelling complex.
AB  - The nucleosome remodelling and histone deacetylase (NuRD; also known as Mi-2)
      complex regulates gene expression at the level of chromatin. The NuRD complex has
      been identified - using both genetic and molecular analyses - as a key
      determinant of differentiation in mouse embryonic stem cells and during
      development in various model systems. Similar to other chromatin remodellers,
      such as SWI/SNF and Polycomb complexes, NuRD has also been implicated in the
      regulation of transcriptional events that are integral to oncogenesis and cancer
      progression. Emerging molecular details regarding the recruitment of NuRD to
      specific loci during development, and the modulation of these events in cancer,
      are used to illustrate how the inappropriate localization of the complex could
      contribute to tumour biology.

PMID- 21734723
TI  - Systems biology: Lethal weaknesses.

PMID- 21734725
TI  - Transcription factors that mediate epithelial-mesenchymal transition lead to
      multidrug resistance by upregulating ABC transporters.
AB  - Development of multidrug resistance (MDR) is a major deterrent in the effective
      treatment of metastatic cancers by chemotherapy. Even though MDR and cancer
      invasiveness have been correlated, the molecular basis of this link remains
      obscure. We show here that treatment with chemotherapeutic drugs increases the
      expression of several ATP binding cassette transporters (ABC transporters)
      associated with MDR, as well as epithelial-mesenchymal transition (EMT) markers,
      selectively in invasive breast cancer cells, but not in immortalized or non
      invasive cells. Interestingly, the mere induction of an EMT in immortalized and
      non-invasive cell lines increased their expression of ABC transporters,
      migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive
      cells by downregulating EMT-inducing transcription factors reduced their
      expression of ABC transporters, invasion, and rendered them more chemosensitive.
      Mechanistically, we demonstrate that the promoters of ABC transporters carry
      several binding sites for EMT-inducing transcription factors, and overexpression
      of Twist, Snail, and FOXC2 increases the promoter activity of ABC transporters.
      Furthermore, chromatin immunoprecipitation studies revealed that Twist binds
      directly to the E-box elements of ABC transporters. Thus, our study identifies
      EMT inducers as novel regulators of ABC transporters, thereby providing molecular
      insights into the long-standing association between invasiveness and MDR.
      Targeting EMT transcription factors could hence serve as novel strategies to curb
      both metastasis and the associated drug resistance.

PMID- 21734724
TI  - Cyclin D as a therapeutic target in cancer.
AB  - Cyclin D1, and to a lesser extent the other D-type cyclins, is frequently
      deregulated in cancer and is a biomarker of cancer phenotype and disease
      progression. The ability of these cyclins to activate the cyclin-dependent
      kinases (CDKs) CDK4 and CDK6 is the most extensively documented mechanism for
      their oncogenic actions and provides an attractive therapeutic target. Is this an
      effective means of targeting the cyclin D oncogenes, and how might the patient
      subgroups that are most likely to benefit be identified?

PMID- 21734726
TI  - Comparative analysis of FV vectors with human alpha- or beta-globin gene
      regulatory elements for the correction of beta-thalassemia.
AB  - beta-Globin locus control region (LCR) sequences have been widely used for the
      regulated expression of the human beta-globin gene in therapeutic viral vectors.
      In this study, we compare the expression of the human beta-globin gene from
      either the HS2/HS3 beta-globin LCR or the HS40 regulatory element from the alpha
      globin locus in the context of foamy virus (FV) vectors for the genetic
      correction of beta-thalassemia. Both regulatory elements expressed comparable
      levels of human beta-globin in a murine erythroleukemic line, whereas in murine
      hematopoietic stem cells the HS40.beta vector proved more efficient in beta
      globin expression and correction of the beta-thalassemia phenotype. Following
      transplantation in the Hbb(th3/+) mouse model, the expression efficiency by the
      two vectors was similar, whereas the HS40.beta vector achieved relatively more
      stable transgene expression. In addition, in an ex vivo assay using CD34+ cells
      from thalassemic patients, both vectors achieved significant human beta-globin
      expression and restoration of the thalassemic phenotype as evidenced by enhanced
      erythropoiesis and decreased apoptosis. Our data suggest that FV vectors with the
      alpha-globin HS40 element can be used as alternative but equally efficient
      vehicles for human beta-globin gene expression for the genetic correction of beta
      thalassemia.

PMID- 21734727
TI  - A Semliki forest virus vector engineered to express IFNalpha induces efficient
      elimination of established tumors.
AB  - Semliki Forest virus (SFV) represents a promising gene therapy vector for tumor
      treatment, because it produces high levels of recombinant therapeutic proteins
      while inducing apoptosis in infected cells. In this study, we constructed a SFV
      vector expressing murine interferon alpha (IFNalpha). IFNalpha displays antitumor
      activity mainly by enhancing an antitumor immune response, as well as by a direct
      antiproliferative effect. In spite of the antiviral activity of IFNalpha, SFV-IFN
      could be produced in BHK cells at high titers. This vector was able to infect TC
      1 cells, a tumor cell line expressing E6 and E7 proteins of human papillomavirus,
      leading to high production of IFNalpha both in vitro and in vivo. When injected
      into subcutaneous TC-1 tumors implanted in mice, SFV-IFN was able to induce an E7
      specific cytotoxic T lymphocyte response, and to modify tumor infiltrating immune
      cells, reducing the percentage of T regulatory cells and activating myeloid
      cells. As a consequence, SFV-IFN was able to eradicate 58% of established tumors
      treated 21 days after implantation with long-term tumor-free survival and very
      low toxicity. SFV-IFN was also able to induce significant antitumor responses in
      a subcutaneous tumor model of murine colon adenocarcimoma. These data suggest
      that local production of IFNalpha by intratumoral injection of recombinant SFV
      IFN could represent a potent new strategy to treat tumors in patients.

PMID- 21734728
TI  - Expression patterns of mRNAs for methanotrophy and thiotrophy in symbionts of the
      hydrothermal vent mussel Bathymodiolus puteoserpentis.
AB  - The hydrothermal vent mussel Bathymodiolus puteoserpentis (Mytilidae) from the
      Mid-Atlantic Ridge hosts symbiotic sulfur- and methane-oxidizing bacteria in its
      gills. In this study, we investigated the activity and distribution of these two
      symbionts in juvenile mussels from the Logatchev hydrothermal vent field (14
      degrees 45'N Mid-Atlantic Ridge). Expression patterns of two key genes for
      chemosynthesis were examined: pmoA (encoding subunit A of the particulate methane
      monooxygenase) as an indicator for methanotrophy, and aprA (encoding the subunit
      A of the dissimilatory adenosine-5'-phosphosulfate reductase) as an indicator for
      thiotrophy. Using simultaneous fluorescence in situ hybridization (FISH) of rRNA
      and mRNA we observed highest mRNA FISH signals toward the ciliated epithelium
      where seawater enters the gills. The levels of mRNA expression differed between
      individual specimens collected in a single grab from the same sampling site,
      whereas no obvious differences in symbiont abundance or distribution were
      observed. We propose that the symbionts respond to the steep temporal and spatial
      gradients in methane, reduced sulfur compounds and oxygen by modifying gene
      transcription, whereas changes in symbiont abundance and distribution take much
      longer than regulation of mRNA expression and may only occur in response to long
      term changes in vent fluid geochemistry.

PMID- 21734729
TI  - Up-regulation of cochlear Hes1 expression in response to noise exposure.
AB  - Hes1, a hairy and enhancer of split homolog, negatively regulates inner ear hair
      cell differentiation. The main objective of this study was to investigate the
      status of the Hes1 gene in the noise-damaged cochlea in relation to the degree of
      noise-induced hearing loss (NIHL). Adult albino guinea pigs were exposed to white
      band noise (115 dB sound pressure level). Noise exposure for either 1 or 3 hours
      induced significant elevations of threshold in auditory brainstem response (ABR)
      compared with unexposed controls. Succinate dehydrogenase staining showed that
      white-band noise exposure caused significant outer hair cell losses. In addition,
      we found significant up-regulations of cochlear Hes1 mRNA and protein expressions
      following acoustic trauma, and Hes1 mRNA expression was positively correlated
      with NIHL. These findings suggest that up-regulation of Hes1 expression in
      response to noise exposure may be one of the underlying mechanisms of NIHL.

PMID- 21734730
TI  - Appearance of singularities of optical fields under torsion of crystals
      containing threefold symmetry axes.
AB  - We present an analysis of the effect of torsion stresses on the spatial
      distribution of optical birefringence in crystals of different point symmetry
      groups. The symmetry requirements needed so that the optical beam carries
      dislocations of the phase front are evaluated for the case when the crystals are
      twisted and the beam closely corresponds to a plane wave. It is shown that the
      torsion stresses can produce screw-edge, pure screw, or pure edge dislocations of
      the phase front in the crystals belonging to cubic and trigonal systems. The
      conditions for appearance of canonical and noncanonical vortices in the
      conditions of crystal torsion are analyzed.

PMID- 21734731
TI  - Method-of-moments formulation for the analysis of plasmonic nano-optical
      antennas.
AB  - We present a surface integral equation (SIE) to model the electromagnetic
      behavior of metallic objects at optical frequencies. The electric and magnetic
      current combined field integral equation considering both tangential and normal
      equations is applied. The SIE is solved by using a method-of-moments (MoM)
      formulation. The SIE-MoM approach is applied only on the material boundary
      surfaces and interfaces, avoiding the cumbersome volumetric discretization of the
      objects and the surrounding space required in differential-equation formulations.
      Some canonical examples have been analyzed, and the results have been compared
      with analytical reference solutions in order to prove the accuracy of the
      proposed method. Finally, two plasmonic Yagi-Uda nanoantennas have been analyzed,
      illustrating the applicability of the method to the solution of real plasmonic
      problems.

PMID- 21734735
TI  - Generalized beam quality factor of aberrated truncated Gaussian laser beams.
AB  - We outline a theory for the calculation of the beam quality factor of an
      aberrated laser beam. We provide closed-form equations that show that the beam
      quality factor of an aberrated Gaussian beam depends on all primary aberrations
      except tilt, defocus, and x-astigmatism. The model is verified experimentally by
      implementing aberrations as digital holograms in the laboratory.

PMID- 21734736
TI  - Digital computation of the complex linear canonical transform.
AB  - An efficient algorithm for the accurate computation of the linear canonical
      transform with complex transform parameters and with complex output variable is
      presented. Sampling issues are discussed and the requirements for different cases
      given. Simulations are provided to validate the results.

PMID- 21734737
TI  - Diffractive properties of obstructed vector Laguerre-Gaussian beam under tight
      focusing condition.
AB  - Diffractive and focusing properties of vector Laguerre-Gaussian beams with
      obstacle are investigated under tight focusing conditions. Using vector
      diffraction theory, intensity and polarization distributions near the focus at
      different orthogonal planes are calculated and analyzed for vector Laguerre
      Gaussian beams. It is observed that the beam is able to compensate the distortion
      produced by obstacles when the size of the obstacle is small. The structural
      changes in the polarization distribution are not the same in different orthogonal
      planes. The polarization characteristics of the beam show a significant change
      when the size of the obstacle is large. A comparative study of the focusing and
      diffractive properties of vector Laguerre-Gaussian and vector Bessel-Gaussian
      beams has also been performed.

PMID- 21734738
TI  - Improving retinal image resolution with iterative weighted shift-and-add.
AB  - High-resolution retinal imaging requires dilating the pupil, and therefore
      exposing more aberrations that blur the image. We developed an image processing
      technique that takes advantage of the natural movement of the eye to average out
      some of the high-order aberrations and to oversample the retina. This method was
      implemented on a long sequence of retinal images of subjects with normal vision.
      We were able to resolve the structures of the size of single cells in the living
      human retina. The improvement of resolution is independent of the acquisition
      method, as long as the image is not warped during scanning. Consequently, even
      better results can be expected by implementing this technique on higher
      resolution images.

PMID- 21734739
TI  - Mean focal length of an aberrated lens.
AB  - We outline an approach for the calculation of the mean focal length of an
      aberrated lens and provide closed-form solutions that show that the focal length
      of the lens is dependent on the presence of defocus, x-astigmatism, and spherical
      aberration. The results are applicable to Gaussian beams in the presence of
      arbitrary-sized apertures. The theoretical results are confirmed experimentally,
      showing excellent agreement. As the final results are in algebraic form, the
      theory may readily be applied in the laboratory if the aberration coefficients of
      the lens are known.

PMID- 21734740
TI  - Digital holographic microscopy with pure-optical spherical phase compensation.
AB  - Telecentric architecture is proposed for circumventing, by the pure-optical
      method, the residual parabolic phase distortion inherent to standard
      configuration of digital holographic microscopy. This optical circumvention
      produces several important advantages. One is that there is no need for computer
      compensation of the parabolic phase during the phase map recovering procedure.
      The other is that in off-axis configuration, the spatial frequency useful domain
      is enlarged. The validity of the method is demonstrated by performing
      quantitative measurement of depth differences with high axial resolution.

PMID- 21734741
TI  - Scattering matrix interpolation from the perturbation method: application to
      calculation of a grating's electromagnetic and scatterometric signatures.
AB  - The scatterometric and electromagnetic signatures of a pattern are computed with
      the perturbation method combined with the Fourier modal method in order to reduce
      computational time. From an electromagnetic point of view, the grating is
      characterized by its scattering matrix, which allows the computation of the
      reflection and transmission coefficients. A slight variation of profile
      parameters or electrical ones provides a small fluctuation of the scattering
      matrix; consequently, an analytical expression of the local behavior of its
      eigenvectors and eigenvalues can be obtained by using a perturbation method.

PMID- 21734742
TI  - Maintaining accuracy of cellular Yule-Nielsen spectral Neugebauer models for
      different ink cartridges using principal component analysis.
AB  - The replacement of used-up ink cartridges is unavoidable, but it makes the
      existing characterization model far from accurate, while recharacterization is
      labor intensive. In this study, we propose a new correction method for cellular
      Yule-Nielsen spectral Neugebauer (CYNSN) models based on principal component
      analysis (PCA). First, a small set of correction samples are predicted, printed
      using new ink cartridges, and then measured. Second, the link between the
      predicted and measured reflectance weights, generated by PCA, is determined. The
      experimental results show that the proposed method provides a significant and
      robust improvement, since not only the color change between original and new inks
      but also the systemic error of CYNSN modelsis taken into account in the method.

PMID- 21734743
TI  - Theoretical study of acousto-optical coherence tomography using random phase
      jumps on ultrasound and light.
AB  - Acousto-optical coherence tomography (AOCT) is a variant of acousto-optic imaging
      (also called ultrasonic modulation imaging) that makes it possible to get the z
      resolution with acoustic and optic continuous wave beams. We describe here
      theoretically the AOCT effect, and we show that the acousto-optic "tagged
      photons" remain coherent if they are generated within a specific z region of the
      sample. We quantify the z selectivity for both the "tagged photon" field and for
      the Lesaffre et al. [Opt. Express 17, 18211 (2009)] photorefractive signal.

PMID- 21734744
TI  - Decoding of depth and motion in ambiguous binocular perception.
AB  - We have shown previously that random dots with an interocular time delay (ITD),
      the time difference of the onset of dots between the two eyes, yield both
      apparent depth and motion, although depth and velocity are covariant and, thus,
      ITD is inherently ambiguous. The depth of random dots with ITD was proportional
      to ITD, suggesting that the visual system assumes a constant velocity of the dots
      and determines depth on the basis of this constant velocity. We performed
      psychophysical experiments to investigate whether subjects perceive a constant
      velocity with a variety of ITDs in random dots aligned along a single vertical
      line that ensures neither apparent motion nor accidental disparity between the
      dots. The results showed that subjects perceive a constant velocity for a variety
      of ITDs with simultaneous perception of depth in proportion to ITD, indicating
      the priority of depth over velocity in ambiguous binocular perception derived
      from ITD.

PMID- 21734745
TI  - Lensless optical data embedding system using concealogram and cascaded digital
      Fresnel hologram.
AB  - A robust lensless optical data embedding system using both the computer-generated
      concealogram and the digital Fresnel hologram (DFH) is proposed. The concealogram
      and the DFH are cascaded as the input and filter planes, respectively. When the
      concealogram is illuminated by a plane wave, the hidden data can be extracted at
      the output plane without using any lenses. The longitudinal positions of the
      filter and the output planes, as well as the wavelength, can be used as the
      secret keys to enhance system security. Furthermore, the robustness of the
      proposed system against noise and distortion is also demonstrated.

PMID- 21734746
TI  - Double helical laser beams based on interfering first-order Bessel beams.
AB  - We demonstrate the generation of a nondiffracting double helical beam using
      axicons and +/-1 vortex phase plates in a common-path interferometric system.
      Using linear diffraction theory, a simple analytical expression describing beam
      propagation is shown to agree with both experiments and Fresnel-diffraction-based
      simulations. Experiments are performed using continuous laser light in addition
      to ultrafast pulses, demonstrating that the common-path arrangement and the
      diffraction theory work equally well for both cases.

PMID- 21734748
TI  - Characteristics of stereo images from detectors in focal plane array.
AB  - The equivalent ray geometry of two horizontally aligned detectors at the focal
      plane of the main antenna in a millimeter wave imaging system is analyzed to
      reveal the reason why the images from the detectors are fused as an image with a
      depth sense. Scanning the main antenna in both horizontal and vertical directions
      makes each detector perform as a camera, and the two detectors can work like a
      stereo camera in the millimeter wave range. However, the stereo camera geometry
      is different from that of the stereo camera used in the visual spectral range
      because the detectors' viewing directions are diverging to each other and they
      are a certain distance apart. The depth sense is mainly induced by the distance
      between detectors. The images obtained from the detectors in the millimeter
      imaging system are perceived with a good depth sense. The disparities responsible
      for the depth sense are identified in the images.

PMID- 21734749
TI  - Semianalytic solution to the problem of scattering from multiple cylinders above
      a perfectly conductive surface.
AB  - We present a novel semianalytical method using multipole expansion technique to
      solve the problem of scattering from multiple perfectly conducting cylinders
      placed above a perfectly conducting ground plane. The idea behind the formulation
      is based on the observation that an infinite flat ground plane can be
      approximated as a cylinder with a radius approaching infinity. Using Green's
      representation of the electromagnetic fields and using addition theorem of Bessel
      function, we expand the fields in terms of multipoles. Applying the appropriate
      boundary condition on the surface of the cylinders and the ground plane based on
      the field polarization results in a set of linear systems of equations containing
      the multipole's coefficients. The technique presented here is highly efficient in
      terms of computing resources, versatile, and accurate. The near fields are
      generated for single and multiple object examples.

PMID- 21734750
TI  - Formulation of light focusing through a plano-convex spherical lens in wave
      optics.
AB  - Focusing of an incident light wave through a plano-convex spherical lens is
      discussed by calculating the light intensity distribution on the lens's optical
      axis after the incident wave is multiply scattered inside the lens. It is found
      that the size and location of the region into which the incident wave is focused
      are determined by two conditions. It is also found that it is possible for the
      wave to be focused into two such regions.

PMID- 21734751
TI  - Analyzing small suprathreshold differences of LCD-generated colors.
AB  - Small suprathreshold color differences around five CIE color centers were
      investigated on a typical liquid crystal display (LCD) with fluorescent backlight
      using the method of constant stimuli. The results were evaluated using probit
      analysis and compared with surface-color differences of the RIT-DuPont dataset.
      We focused especially on the relationship between T50 distances obtained from LCD
      and surface-color stimuli and on the influence of the display's narrowband
      primaries and its relatively low luminance level on interobserver uncertainty.
      The low luminance level of the LCD decreases the perceived color differences.
      However, considering the visual uncertainty of the experimental data, we could
      not reject the hypothesis that T50 distances from the RIT-DuPont and our
      experiment agree up to a constant scaling factor. In addition, we found
      significantly higher interobserver variability in the estimation of small color
      differences if the colors are viewed on an LCD. There are some indications that
      color-difference perception might be influenced by individual color-matching
      functions and, thus, by the spectral power distribution of the stimuli. We
      provide the experimental data, including all spectral stimuli shown to the
      observers, on our website.

PMID- 21734752
TI  - Fluorescence lifetime optical tomography in weakly scattering media in the
      presence of highly scattering inclusions.
AB  - We consider the problem of fluorescence lifetime optical tomographic imaging in a
      weakly scattering medium in the presence of highly scattering inclusions. We
      suggest an approximation to the radiative transfer equation, which results from
      the assumption that the transport coefficient of the scattering media differs by
      an order of magnitude for weakly and highly scattering regions. The image
      reconstruction algorithm is based on the variational framework and employs
      angularly selective intensity measurements. We present numerical simulation of
      light scattering in a weakly scattering medium that embeds highly scattering
      objects. Our reconstruction algorithm is verified by recovering optical and
      fluorescent parameters from numerically simulated datasets.

PMID- 21734754
TI  - Scattering of a partially coherent Gaussian-Schell beam from a diffuse target in
      slant atmospheric turbulence.
AB  - On the basis of the extended Huygens-Fresnel principle, the scattering of
      partially coherent Gaussian-Schell-model (GSM) beams from a diffuse target in
      slant double-passage atmospheric turbulence is studied and compared with that of
      fully coherent Gaussian beams. Using the cross-spectral density function of the
      GSM beams, we derive the expressions of the mutual coherence function, angle-of
      arrival fluctuation, and covariance and variance of the intensity of the
      scattered field, taking into account the fluctuations of both the log-amplitude
      and phase. The numerical results are presented, and the influences of the
      wavelength, propagation distance, and waist radius on scattering properties are
      discussed. The perturbation region of the normalized intensity variance of the
      partially coherent GSM beam is smaller than that of the fully coherent Gaussian
      beam at the middle turbulence level. The normalized intensity variance of long
      distance beam propagation is smaller than that of beam propagation along a short
      distance.

PMID- 21734756
TI  - Future perfect? Improving preparedness through the experiences of the influenza A
      (H1N1) 2009 pandemic.

PMID- 21734757
TI  - Expectations for the United Nations high-level meeting on noncommunicable
      diseases.

PMID- 21734759
TI  - Brazil targets drink driving on the road to fewer deaths.

PMID- 21734760
TI  - Dengue vaccine roll-out: getting ahead of the game.

PMID- 21734761
TI  - Projections of global health outcomes from 2005 to 2060 using the International
      Futures integrated forecasting model.
AB  - OBJECTIVE: To develop an integrated health forecasting model as part of the
      International Futures (IFs) modelling system. METHODS: The IFs model begins with
      the historical relationships between economic and social development and cause
      specific mortality used by the Global Burden of Disease project but builds
      forecasts from endogenous projections of these drivers by incorporating forward
      linkages from health outcomes back to inputs like population and economic growth.
      The hybrid IFs system adds alternative structural formulations for causes not
      well served by regression models and accounts for changes in proximate health
      risk factors. Forecasts are made to 2100 but findings are reported to 2060.
      FINDINGS: The base model projects that deaths from communicable diseases (CDs)
      will decline by 50%, whereas deaths from both non-communicable diseases (NCDs)
      and injuries will more than double. Considerable cross-national convergence in
      life expectancy will occur. Climate-induced fluctuations in agricultural yield
      will cause little excess childhood mortality from CDs, although other climate
      health pathways were not explored. An optimistic scenario will produce 39 million
      fewer deaths in 2060 than a pessimistic one. Our forward linkage model suggests
      that an optimistic scenario would result in a 20% per cent increase in gross
      domestic product (GDP) per capita, despite one billion additional people.
      Southern Asia would experience the greatest relative mortality reduction and the
      largest resulting benefit in per capita GDP. CONCLUSION: Long-term, integrated
      health forecasting helps us understand the links between health and other markers
      of human progress and offers powerful insight into key points of leverage for
      future improvements.

PMID- 21734762
TI  - Potential effect of the World Health Organization's 2011-2015 global leprosy
      strategy on the prevalence of grade 2 disability: a trend analysis.
AB  - OBJECTIVE: To assess different countries' chances of attaining the 2011-2015
      global leprosy target set by the World Health Organization (WHO) and to assess
      the strategy's effect on the prevalence of grade 2 disability (G2D). METHODS:
      Trends in G2D rate were analysed for Brazil, China, India and Thailand and
      figures were compared with the WHO target: a 35% decrease by 2015 relative to the
      2010 baseline. To estimate the prevalence of G2D in 2015 and 2035 for each
      country three assumptions were made: (i) maintenance of the current trend; (ii)
      attainment of the WHO target, and (iii) reduction of G2D by 50% every 5 years
      relative to 2010. FINDINGS: Since 1995, the G2D rate has decreased every 5 years
      in Brazil, China, India and Thailand by 12.7% (95% confidence interval, CI: 6.6
      18.3), 7.7% (95% CI: 1.1-12.8), 53.7% (95% CI: 38.1-65.4) and 35.9% (95% CI: 23.4
      46.3), respectively. New cases with G2D detected after 2010 will contribute 15%
      (Brazil), 3% (China), 2.5% (India) and 4% (Thailand) to the total prevalence of
      G2D in 2015. If no policies are changed, between 2015 and 2035, the prevalence of
      G2D will decrease by more than half in China, India and Thailand, and by 16% in
      Brazil. CONCLUSION: The implications of attaining the WHO target are different
      for each country and using indicators other than G2D prevalence will help monitor
      progress. The strategy will not immediately reduce the prevalence of G2D, but if
      it is applied consistently over the next 25 years, its long-term effect can be
      substantial.

PMID- 21734763
TI  - Effects of a conditional cash transfer programme on child nutrition in Brazil.
AB  - OBJECTIVE: To examine the association between Brazil's Bolsa Familia programme
      (BFP), which is the world's largest conditional cash transfer programme, and the
      anthropometric indicators of nutritional status in children. METHODS: Using the
      opportunity provided by vaccination campaigns, the Brazilian government promotes
      Health and Nutrition Days to estimate the prevalence of anthropometric deficits
      in children. Data collected in 2005-2006 for 22 375 impoverished children under 5
      years of age were employed to estimate nutritional outcomes among recipients of
      Bolsa Familia. All variables under study, namely child birth weight, lack of
      birth certificate, educational level and gender of family head, access to piped
      water and electricity, height for age, weight for age and weight for height, were
      converted into binary variables for regression analysis. FINDINGS: Children from
      families exposed to the BFP were 26% more likely to have normal height for age
      than those from non-exposed families; this difference also applied to weight for
      age. No statistically significant deficit in weight for height was found.
      Stratification by age group revealed 19% and 41% higher odds of having normal
      height for age at 12-35 and 36-59 months of age, respectively, in children
      receiving Bolsa Familia, and no difference at 0-11 months of age. CONCLUSION: The
      BFP can lead to better nutritional outcomes in children 12 to 59 months of age.
      Longitudinal studies are needed to confirm these findings.

PMID- 21734764
TI  - Cost-effectiveness of parenteral artesunate for treating children with severe
      malaria in sub-Saharan Africa.
AB  - OBJECTIVE: To explore the cost-effectiveness of parenteral artesunate for the
      treatment of severe malaria in children and its potential impact on hospital
      budgets. METHODS: The costs of inpatient care of children with severe malaria
      were assessed in four of the 11 sites included in the African Quinine Artesunate
      Malaria Treatment trial, conducted with over 5400 children. The drugs, laboratory
      tests and intravenous fluids provided to 2300 patients from admission to
      discharge were recorded, as was the length of inpatient stay, to calculate the
      cost of inpatient care. The data were matched with pooled clinical outcomes and
      entered into a decision model to calculate the cost per disability-adjusted life
      year (DALY) averted and the cost per death averted. FINDINGS: The mean cost of
      treating severe malaria patients was similar in the two study groups: 63.5 United
      States dollars (US$) (95% confidence interval, CI: 61.7-65.2) in the quinine arm
      and US$ 66.5 (95% CI: 63.7-69.2) in the artesunate arm. Children treated with
      artesunate had 22.5% lower mortality than those treated with quinine and the same
      rate of neurological sequelae: (artesunate arm: 2.3 DALYs per patient; quinine
      arm: 3.0 DALYs per patient). Compared with quinine as a baseline, artesunate
      showed an incremental cost per DALY averted and an incremental cost per death
      averted of US$ 3.8 and US$ 123, respectively. CONCLUSION: Artesunate is a highly
      cost-effective and affordable alternative to quinine for treating children with
      severe malaria. The budgetary implications of adopting artesunate for routine use
      in hospital-based care are negligible.

PMID- 21734765
TI  - Presumptive diagnosis of severe HIV infection to determine the need for
      antiretroviral therapy in children less than 18 months of age.
AB  - OBJECTIVE: To develop a new algorithm for the presumptive diagnosis of severe
      disease associated with human immunodeficiency virus (HIV) infection in children
      less than 18 months of age for the purpose of identifying children who require
      antiretroviral therapy (ART). METHODS: A conditional probability model was
      constructed and non-virologic parameters in various combinations were tested in a
      hypothetical cohort of 1000 children aged 6 weeks, 6 months and 12 months to
      assess the sensitivity, specificity, and positive and negative predictive values
      of these algorithms for identifying children in need of ART. The modelled
      parameters consisted of clinical criteria, rapid HIV antibody testing and CD4+ T
      lymphocyte (CD4) count. FINDINGS: In children younger than 18 months, the best
      performing screening algorithm, consisting of clinical symptoms plus antibody
      testing plus CD4 count, showed a sensitivity ranging from 71% to 80% and a
      specificity ranging from 92% to 99%. Positive and negative predictive values were
      between 61% and 97% and between 95% and 96%, respectively. In the absence of
      virologic tests, this alternate algorithm for the presumptive diagnosis of severe
      HIV disease makes it possible to correctly initiate ART in 91% to 98% of HIV
      positive children who are at highest risk of dying. CONCLUSION: The algorithms
      presented in this paper have better sensitivity and specificity than clinical
      parameters, with or without rapid HIV testing, for the presumptive diagnosis of
      severe disease in HIV-positive children less than 18 months of age. If
      implemented, they can increase the number of HIV-positive children successfully
      initiated on ART.

PMID- 21734766
TI  - Effect of deep tube well use on childhood diarrhoea in Bangladesh.
AB  - OBJECTIVE: To determine whether the installation of deep tube wells to reduce
      exposure to groundwater arsenic in rural Bangladesh had an effect on the
      incidence of childhood diarrhoeal disease. METHODS: Episodes of diarrhoeal
      disease in children aged under 5 years that occurred on one specified day each
      month between 2005 and 2006 were reported to community health workers for six
      rural villages. A geographical information system containing details of household
      water use and sanitation in the villages was built using data obtained by a
      global positioning system survey. The information system also included health,
      spatial and demographic data. A field survey was carried out to determine whether
      households obtained drinking water from deep tube wells installed in 2005. The
      effect of deep tube well use on the incidence of childhood diarrhoea was assessed
      using a random effects negative binomial regression model. FINDINGS: The risk of
      childhood diarrhoea was 46% lower in the 179 households that used a deep tube
      well than in the 364 that used a shallow tube well (P=0.032). Neither
      socioeconomic status, latrine density, population density nor study year had a
      significant influence on disease risk. The incidence of childhood diarrhoea
      declined dramatically between 2005 and 2006, irrespective of water source.
      CONCLUSION: The introduction of deep tube wells to reduce arsenic in drinking
      water in rural Bangladesh had the additional benefit of lowering the incidence of
      diarrhoea among young children.

PMID- 21734767
TI  - Barriers to immunization among children of migrant workers from Myanmar living in
      Tak province, Thailand.
AB  - PROBLEM: Immunization is a cost-effective means of improving child survival but
      implementation of programmes in low- and middle-income countries is variable.
      Children of migrants are less likely to be immunized. APPROACH: The qualitative
      study aimed to identify barriers to the successful implementation of migrant
      immunization programmes in Tak province, Thailand. We ran a total of 53 focus
      groups involving 371 participants in three sites. LOCAL SETTING: Tak province in
      Thailand borders Myanmar and has an estimated 200,000 migrants from Myanmar.
      Vaccine-preventable diseases are a documented cause of morbidity in this
      population but there is no systematic or coordinated immunization programme in
      the area. RELEVANT CHANGES: As a result of the findings, the subsequent
      immunization campaign targeted children in school to overcome those barriers of
      distance to immunization services, fear of arrest, not remembering immunization
      appointments, and the disruption of parental work. The campaigns also included
      immunization education for both parents and teachers. LESSONS LEARNT: Migrant
      parents identified similar barriers to accessing childhood immunization
      programmes as migrant populations elsewhere in the world, although a unique
      barrier identified by parents from Myanmar was "fear of arrest". The subsequent
      school-based strategy to overcome these barriers appears to be effective.

PMID- 21734768
TI  - The elusive definition of pandemic influenza.
AB  - There has been considerable controversy over the past year, particularly in
      Europe, over whether the World Health Organization (WHO) changed its definition
      of pandemic influenza in 2009, after novel H1N1 influenza was identified. Some
      have argued that not only was the definition changed, but that it was done to
      pave the way for declaring a pandemic. Others claim that the definition was never
      changed and that this allegation is completely unfounded. Such polarized views
      have hampered our ability to draw important conclusions. This impasse, combined
      with concerns over potential conflicts of interest and doubts about the
      proportionality of the response to the H1N1 influenza outbreak, has undermined
      the public trust in health officials and our collective capacity to effectively
      respond to future disease threats. WHO did not change its definition of pandemic
      influenza for the simple reason that it has never formally defined pandemic
      influenza. While WHO has put forth many descriptions of pandemic influenza, it
      has never established a formal definition and the criteria for declaring a
      pandemic caused by the H1N1 virus derived from "pandemic phase" definitions, not
      from a definition of "pandemic influenza". The fact that despite ten years of
      pandemic preparedness activities no formal definition of pandemic influenza has
      been formulated reveals important underlying assumptions about the nature of this
      infectious disease. In particular, the limitations of "virus-centric" approaches
      merit further attention and should inform ongoing efforts to "learn lessons" that
      will guide the response to future outbreaks of novel infectious diseases.

PMID- 21734769
TI  - Health is more than influenza.

PMID- 21734770
TI  - Pandemic influenza and its definitional implications.

PMID- 21734771
TI  - The classical definition of a pandemic is not elusive.

PMID- 21734772
TI  - Living forwards, understanding backwards.

PMID- 21734773
TI  - Planning for uncertainty: a European approach to informing responses to the
      severity of influenza epidemics and pandemics.

PMID- 21734774
TI  - Interplay among cellular polarization, lipoprotein metabolism and hepatitis C
      virus entry.
AB  - Hepatitis C virus (HCV) infects more than three million new individuals worldwide
      each year. In a high percentage of patients, acute infections become chronic,
      eventually progressing to fibrosis, cirrhosis, and hepatocellular carcinoma.
      Given the lack of effective prophylactic or therapeutic vaccines, and the limited
      sustained virological response rates to current therapies, new approaches are
      needed to prevent, control, and clear HCV infection. Entry into the host cell,
      being the first step of the viral cycle, is a potential target for the design of
      new antiviral compounds. Despite the recent discovery of the tight junction
      associated proteins claudin-1 and occludin as HCV co-receptors, which is an
      important step towards the understanding of HCV entry, the precise mechanisms are
      still largely unknown. In addition, increasing evidence indicates that tools that
      are broadly employed to study HCV infection do not accurately reflect the real
      process in terms of viral particle composition and host cell phenotype. Thus,
      systems that more closely mimic natural infection are urgently required to
      elucidate the mechanisms of HCV entry, which will in turn help to design
      antiviral strategies against this part of the infection process.

PMID- 21734775
TI  - Inflammatory bowel disease in adolescents: what problems does it pose?
AB  - Adolescents with inflammatory bowel disease face daily and long-term challenges
      that may be difficult for teenagers to manage. The developmental and psychosocial
      changes unique to this age group include becoming more autonomous and being more
      vulnerable to peer influence. These changes may lead to problems in medical
      management such as poor medication adherence and risky behavior. Being aware of
      these issues will help the medical team provide anticipatory guidance to address
      these concerns.

PMID- 21734776
TI  - Inflammatory bowel disease in pregnancy.
AB  - Crohn's disease and ulcerative colitis affect women in their child-bearing years.
      Family planning has come to be a common discussion between the gastroenterologist
      and the inflammatory bowel disease (IBD) patient. Disease control prior to
      desired conception and throughout pregnancy is the most important thing to keep
      in mind when caring for the IBD patient. Continued medical management during
      pregnancy is crucial in optimizing outcomes. Studies indicate that quiescent
      disease prior to conception infer the best pregnancy outcomes, similar to those
      in the general population. Active disease prior to and during pregnancy, can lead
      to complications such as pre-term labor, low birth weight, and small for
      gestational age infants. Although there are no definitive long term effects of
      pregnancy on IBD, there are some limited studies that suggest that it may alter
      the disease course. Understanding the literature and its limitations is important
      in the modern era of IBD care. Educating the patient and taking a team approach
      with the obstetrician will help achieve successful outcomes for mother and baby.

PMID- 21734777
TI  - Extraintestinal manifestations of inflammatory bowel disease: do they influence
      treatment and outcome?
AB  - Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases
      that often involve organs other than those of the gastrointestinal tract. Immune
      related extraintestinal manifestations (EIMs) are usually related to disease
      activity, but sometimes may take an independent course. Globally, about one third
      of patients develop these systemic manifestations. Phenotypic classification
      shows that certain subsets of patients are more susceptible to developing EIMs,
      which frequently occur simultaneously in the same patient overlapping joints,
      skin, mouth, and eyes. The clinical spectrum of these manifestations varies from
      mild transitory to very severe lesions, sometimes more incapacitating than the
      intestinal disease itself. The great majority of these EIMs accompany the
      activity of intestinal disease and patients run a higher risk of a severe
      clinical course. For most of the inflammatory EIMs, the primary therapeutic
      target remains the bowel. Early aggressive therapy can minimize severe
      complications and maintenance treatment has the potential to prevent some
      devastating consequences.

PMID- 21734778
TI  - Inflammatory bowel disease in travelers: choosing the right vaccines and check
      ups.
AB  - The majority of patients with inflammatory bowel disease (IBD) achieve good
      control of the inflammatory activity using available therapies. When remission is
      achieved and quality of life recovered, a considerable proportion of IBD patients
      express their desire to travel abroad, be it for business, academic or leisure
      purposes. Their physicians should help and encourage them whenever possible.
      However, preventive measures are warranted to minimize the risk, since IBD
      patients are exposed to the same infections affecting the general population,
      plus opportunistic infections (OI) related to the immunosuppression. There are a
      large number of potential OI that might affect patients with IBD. The true
      prevalence of these infections is unknown, and can vary from country to country.
      Therefore, reactivation or de novo acquisition of infections such as
      tuberculosis, malaria, and viral hepatitis will be much more frequent in endemic
      areas. Therefore, physicians should be aware of these aspects when planning
      specific preventive measures for patients traveling to a particular country. This
      includes good control of environmental exposure, chemoprophylaxis when indicated,
      and the use of a specific vaccination program to prevent endemic infections. In
      addition, it should be noted that, though the risk of acquiring an infectious
      disease is probably greater for IBD patients traveling from a developed to a
      developing country, the inverse situation can also occur; it depends on the
      previous acquired immunity of the host against infections in any particular
      environment.

PMID- 21734779
TI  - Familial aggregation in inflammatory bowel disease: is it genes or environment?
AB  - Inflammatory bowel disease (IBD) develops in genetically susceptible individuals
      due to the influence of environmental factors, leading to an abnormal recognition
      of microbiota antigens by the innate immune system which triggers an exaggerated
      immune response and subsequent bowel tissue damage. IBD has been more frequently
      found in families, an observation that could be due to either genetic,
      environmental or both types of factors present in these families. In addition to
      expanding our knowledge on IBD pathogenesis, defining the specific contribution
      to familial IBD of each one of these factors might have also clinical usefulness.
      We review the available evidence on familial IBD pathogenesis.

PMID- 21734780
TI  - Comorbidity in inflammatory bowel disease.
AB  - Patients with inflammatory bowel disease (IBD) can be affected by other unrelated
      diseases. These are called comorbid conditions, and can include any secondary
      health problem that affects a person suffering from a primary or main disease,
      and which is neither linked physiopathologically to the primary condition, nor is
      it due to the treatments used for the primary condition or to its long-term
      anatomical or physiological consequences. Different comorbid conditions, as well
      as their influence on IBD, are discussed.

PMID- 21734781
TI  - Old-age inflammatory bowel disease onset: a different problem?
AB  - Inflammatory bowel disease (IBD) in patients aged > 60 accounts for 10%-15% of
      cases of the disease. Diganostic methods are the same as for other age groups.
      Care has to be taken to distinguish an IBD colitis from other forms of colitis
      that can mimick clinically, endoscopically and even histologically the IBD
      entity. The clinical pattern in ulcerative colitis (UC) is proctitis and left
      sided UC, while granulomatous colitis with an inflammatory pattern is more common
      in Crohn's disease (CD). The treatment options are those used in younger
      patients, but a series of considerations related to potential pharmacological
      interactions and side effects of the drugs must be taken into account. The safety
      profile of conventional immunomodulators and biological therapy is acceptable but
      more data are required on the safety of use of these drugs in the elderly
      population. Biological therapy has risen question on the possibility of increased
      side effects, however this needs to be confirmed. Adherence to performing all the
      test prior to biologic treatment administration is very important. The overall
      response to treatment is similar in the different patient age groups but elderly
      patients have fewer recurrences. The number of hospitalizations in patients > 65
      years is greater than in younger group, accounting for 25% of all admissions for
      IBD. Mortality is similar in UC and slightly higher in CD, but significantly
      increased in hospitalized patients. Failure of medical treatment continues to be
      the most common indication for surgery in patients aged > 60 years. Age is not
      considered a contraindication for performing restorative proctocolectomy with an
      ileal pouch-anal anastomosis. However, incontinence evaluation should be taken
      into account an individualized options should be considered.

PMID- 21734782
TI  - Ulcerative colitis in smokers, non-smokers and ex-smokers.
AB  - Smoking is a major environmental factor that interferes in the establishment and
      clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status
      impact in the development of UC is reviewed, showing that current smoking has a
      protective association with UC. Similarly, being a former smoker is associated
      with an increased risk of UC. The concept that smoking could have a role in
      determining the inflammatory bowel disease phenotype is also discussed. Gender
      may also be considered, as current smoking delays disease onset in men but not in
      women. No clear conclusions can be driven from the studies trying to clarify
      whether childhood passive smoking or prenatal smoke exposure have an influence on
      the development of UC, mainly due to methodology flaws. The influence of smoking
      on disease course is the second aspect analysed. Some studies show a disease
      course more benign in smokers that in non-smokers, with lower hospitalizations
      rates, less flare-ups, lower use of oral steroids and even less risk of proximal
      extension. This is not verified by some other studies. Similarly, the rate of
      colectomy does not seem to be determined by the smoking status of the patient.
      The third issue reviewed is the use of nicotine as a therapeutic agent. The place
      of nicotine in the treatment of UC is unclear, although it could be useful in
      selected cases, particularly in recent ex-smokers with moderate but refractory
      attacks of UC. Finally, the effect of smoking cessation in UC patients is
      summarised. Given that smoking represents a major worldwide cause of death, for
      inpatients with UC the risks of smoking far outweigh any possible benefit. Thus,
      physicians should advise, encourage and assist UC patients who smoke to quit.

PMID- 21734783
TI  - miRNA studies in in vitro and in vivo activated hepatic stellate cells.
AB  - AIM: To understand which and how different miRNAs are implicated in the process
      of hepatic stellate cell (HSC) activation. METHODS: We used microarrays to
      examine the differential expression of miRNAs during in vitro activation of
      primary HSCs (pHSCs). The transcriptome changes upon stable transfection of rno
      miR-146a into an HSC cell line were studied using cDNA microarrays. Selected
      differentially regulated miRNAs were investigated by quantitative real-time
      polymerase chain reaction during in vivo HSC activation. The effect of miRNA
      mimics and inhibitor on the in vitro activation of pHSCs was also evaluated.
      RESULTS: We found that 16 miRNAs were upregulated and 26 were downregulated
      significantly in 10-d in vitro activated pHSCs in comparison to quiescent pHSCs.
      Overexpression of rno-miR-146a was characterized by marked upregulation of tissue
      inhibitor of metalloproteinase-3, which is implicated in the regulation of tumor
      necrosis factor-alpha activity. Differences in the regulation of selected miRNAs
      were observed comparing in vitro and in vivo HSC activation. Treatment with miR
      26a and 29a mimics, and miR-214 inhibitor during in vitro activation of pHSCs
      induced significant downregulation of collagen type I transcription. CONCLUSION:
      Our results emphasize the different regulation of miRNAs in in vitro and in vivo
      activated pHSCs. We also showed that miR-26a, 29a and 214 are involved in the
      regulation of collagen type I mRNA.

PMID- 21734784
TI  - Influence of chitosan nanofiber scaffold on porcine endogenous retroviral
      expression and infectivity in pig hepatocytes.
AB  - AIM: To investigate the influence of chitosan nanofiber scaffold on the
      production and infectivity of porcine endogenous retrovirus (PERV) expressed by
      porcine hepatocytes. METHODS: Freshly isolated porcine hepatocytes were cultured
      with or without chitosan nanofiber scaffold (defined as Nano group and Hep group)
      for 7 d. The daily collection of culture medium was used to detect reverse
      transcriptase (RT) activity with RT activity assay kits and PERV RNA by reverse
      transcription-polymerase chain reaction (PCR) and real time PCR with the PERV
      specific primers. And Western blotting was performed with the lysates of daily
      retrieved cells to determine the PERV protein gag p30. Besides, the in-vitro
      infectivity of the supernatant was tested by incubating the human embryo kidney
      293 (HEK293) cells. RESULTS: The similar changing trends between two groups were
      observed in real time PCR, RT activity assay and Western blotting. Two peaks of
      PERV expression at 10H and Day 2 were found and followed by a regular decline. No
      significant difference was found between two groups except the significantly high
      level of PERV RNA at Day 6 and PERV protein at Day 5 in Nano group than that in
      Hep group. And in the in-vitro infection experiment, no HEK293 cell was infected
      by the supernatant. CONCLUSION: Chitosan nanofiber scaffold might prolong the
      PERV secreting time in pig hepatocytes but would not obviously influence its
      productive amount and infectivity, so it could be applied in the bioartificial
      liver without the increased risk of the virus transmission.

PMID- 21734785
TI  - Targeting key signalling pathways in oesophageal adenocarcinoma: a reality for
      personalised medicine?
AB  - Cancer treatments are rapidly changing. Curative treatment for oesophageal
      adenocarcinoma currently involves surgery and cytotoxic chemotherapy or
      chemoradiotherapy. Outcomes for both regimes are generally poor as a result of
      tumor recurrence. We have reviewed the key signalling pathways associated with
      oesophageal adenocarcinomas and discussed the recent trials of novel agents that
      attempt to target these pathways. There are many trials underway with the aim of
      improving survival in oesophageal cancer. Currently, phase 2 and 3 trials are
      focused on MAP kinase inhibition, either through inhibition of growth factor
      receptors or signal transducer proteins. In order to avoid tumor resistance, it
      appears to be clear that targeted therapy will be needed to combat the multiple
      signalling pathways that are in operation in oesophageal adenocarcinomas. This
      may be achievable in the future with the advent of gene signatures and a
      combinatorial approach.

PMID- 21734786
TI  - Need for a comprehensive medical approach to the neuro-immuno-gastroenterology of
      irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is defined by the Rome III criteria as symptoms of
      recurrent abdominal pain or discomfort with the onset of a marked change in bowel
      habits with no evidence of an inflammatory, anatomic, metabolic, or neoplastic
      process. As such, many clinicians regard IBS as a central nervous system problem
      of altered pain perception. Here, we review the recent literature and discuss the
      evidence that supports an organic based model, which views IBS as a complex,
      heterogeneous, inter-dependent, and multi-variable inflammatory process along the
      neuronal-gut axis. We delineate the organic pathophysiology of IBS, demonstrate
      the role of inflammation in IBS, review the possible differences between adult
      and pediatric IBS, discuss the merits of a comprehensive treatment model as
      taught by the Institute of Functional Medicine, and describe the potential for
      future research for this syndrome.

PMID- 21734788
TI  - Streptozotocin-induced expression of Ngn3 and Pax4 in neonatal rat pancreatic
      alpha-cells.
AB  - AIM: To investigate the mechanism behind beta-cell regeneration in neonatal rat
      pancreas treated with streptozotocin (STZ). METHODS: Neonatal Sprague Dawley rats
      were intraperitoneally injected with 70 mg/kg STZ. Body weight, pancreas weight
      and blood glucose were recorded every two days after the treatment. To identify
      the expression and location of transcription factors in the rat pancreas, double
      immunofluorescent staining was performed using antibodies to specific cell
      markers and transcription factors. RESULTS: Expression of Neurogenin 3 (Ngn3), a
      marker for endocrine precursor cells, was observed by immunofluorescence in a few
      beta-cells and many alpha-cells. The expression reached a peak 12 d after
      treatment. Pax4, a transcription factor that lies downstream of Ngn3 and plays an
      important role in beta-cell differentiation, was also expressed in the alpha
      cells of STZ-treated rats. We did not observe significant changes in Nkx6.1,
      which is essential for beta-cell maturation in the treated rats. CONCLUSION:
      alpha-cells dedifferentiated into endocrine precursor cells and acquired the
      ability to dedifferentiate in the neonatal rat pancreas after STZ treatment.

PMID- 21734787
TI  - Adiponectin, a key adipokine in obesity related liver diseases.
AB  - Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis, non
      alcoholic steatohepatitis (NASH), and progressive liver fibrosis is considered
      the most common liver disease in western countries. Fatty liver is more prevalent
      in overweight than normal-weight people and liver fat positively correlates with
      hepatic insulin resistance. Hepatic steatosis is regarded as a benign stage of
      NAFLD but may progress to NASH in a subgroup of patients. Besides liver biopsy no
      diagnostic tools to identify patients with NASH are available, and no effective
      treatment has been established. Visceral obesity is a main risk factor for NAFLD
      and inappropriate storage of triglycerides in adipocytes and higher
      concentrations of free fatty acids may add to increased hepatic lipid storage,
      insulin resistance, and progressive liver damage. Most of the adipose tissue
      derived proteins are elevated in obesity and may contribute to systemic
      inflammation and liver damage. Adiponectin is highly abundant in human serum but
      its levels are reduced in obesity and are even lower in patients with hepatic
      steatosis or NASH. Adiponectin antagonizes excess lipid storage in the liver and
      protects from inflammation and fibrosis. This review aims to give a short survey
      on NAFLD and the hepatoprotective effects of adiponectin.

PMID- 21734789
TI  - Pathological and MR-DWI study of the acute hepatic injury model after stem cell
      transplantation.
AB  - AIM: To investigate apparent diffusion coefficient (ADC) values as an indication
      of reconditioning of acute hepatic injury (AHI) after allogeneic mononuclear bone
      marrow cell (MBMC) transplantation. METHODS: Three groups were used in our study:
      a cell transplantation group (n = 21), transplantation control group (n = 21) and
      normal control group (n = 10). AHI model rabbits in the cell transplantation
      group were injected with 5 mL of MBMC suspension at multiple sites in the liver
      and the transplantation controls were injected with 5 mL D-Hanks solution. At the
      end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell
      transplantation group and transplantation control group for magnetic resonance
      diffusion-weighted imaging (MR-DWI) and measurement of the mean ADC values of
      injured livers. After MR-DWI examination, the rabbits were sacrificed and the
      livers subjected to pathological examination. Ten healthy rabbits from the normal
      control group were used for MR-DWI examination and measurement of the mean ADC
      value of normal liver. RESULTS: At all time points, the liver pathological scores
      from the cell transplantation group were significantly lower than those in the
      transplantation control group (27.14 +/- 1.46 vs 69.29 +/- 6.16, 22.29 +/- 2.29
      vs 57.00 +/- 1.53, 19.00 +/- 2.31 vs 51.86 +/- 6.04, P = 0.000). The mean ADC
      values of the cell transplantation group were significantly higher than the
      transplantation control group ((1.07 +/- 0.07) * 10-3 mm2/s vs (0.69 +/- 0.05) *
      10-3 mm2/s, (1.41 +/- 0.04) * 10-3 mm2/s vs (0.84 +/- 0.06) * 10-3 mm2/s, (1.68
      +/- 0.04) * 10-3 mm2/s vs (0.86 +/- 0.04) * 10-3 mm2/s, P = 0.000). The
      pathological scores of the cell transplantation group and transplantation control
      group gradually decreased. However, their mean ADC values gradually increased to
      near that of the normal control. At the end of the 1st wk, the mean ADC values of
      the cell transplantation group and transplantation control group were
      significantly lower than those of the normal control group [(1.07 +/- 0.07) * 10
      3 mm2/s vs (1.76 +/- 0.03) * 10-3 mm2/s, (0.69 +/- 0.05) * 10-3 mm2/s vs (1.76 +/
      0.03) * 10-3 mm2/s, P = 0.000]. At any 2 time points, the pathological scores
      and the mean ADC values of the cell transplantation group were significantly
      different (P = 0.000). At the end of the 1st wk, the pathological scores and the
      mean ADC values of the transplantation control group were significantly different
      from those at the end of the 2nd and 4th wk (P = 0.000). However, there was no
      significant difference between the 2nd and 4th wk (P = 0.073 and 0.473,
      respectively). The coefficient of correlation between the pathological score and
      the mean ADC value in the cell transplantation group was -0.883 (P = 0.000) and 
      0.762 (P = 0.000) in the transplantation control group. CONCLUSION: Tracking the
      longitudinally dynamic change in the mean ADC value of the AHI liver may reflect
      hepatic injury reconditioning after allogeneic MBMC transplantation.

PMID- 21734790
TI  - NOD2 and ATG16L1 polymorphisms affect monocyte responses in Crohn's disease.
AB  - AIM: To assess whether polymorphisms in NOD2 and ATG16L1 affect cytokine
      responses and mycobacterium avium subspecies paratuberculosis (MAP) survival in
      monocytes from Crohn's disease (CD) patients. METHODS: Monocytes were isolated
      from peripheral blood of CD patients of known genotype for common single
      nucleotide polymorphisms of NOD2 and ATG16L1. Monocytes were challenged with MAP
      and bacterial persistence assessed at subsequent time-points. Cytokine responses
      were assayed using a Milliplex multi-analyte profiling assay for 13 cytokines.
      RESULTS: Monocytes heterozygous for a NOD2 polymorphism (R702W, P268S, or 1007fs)
      were more permissive for growth of MAP (P = 0.045) than those without. There was
      no effect of NOD2 genotype on subsequent cytokine expression. The T300A
      polymorphism of ATG16L1 did not affect growth of MAP in our model (P = 0.175),
      but did increase expression of cytokines interleukin (IL)-10 (P = 0.047) and IL-6
      (P = 0.019). CONCLUSION: CD-associated polymorphisms affected the elimination of
      MAP from ex vivo monocytes (NOD2), or expression of certain cytokines (ATG16L1),
      implying independent but contributory roles in the pathogenesis of CD.

PMID- 21734791
TI  - Is the Schatzki ring a unique esophageal entity?
AB  - AIM: To study, whether the association of Schatzki rings with other esophageal
      disorders support one of the theories about its etiology. METHODS: From 1987
      until 2007, all patients with newly diagnosed symptomatic Schatzki rings (SRs)
      were prospectively registered and followed. All of them underwent structured
      interviews with regards to clinical symptoms, as well as endoscopic and/or
      radiographic examinations. Endoscopic and radiographic studies determined the
      presence of an SR and additional morphological abnormalities. RESULTS: One
      hundred and sixty-seven patients (125 male, 42 female) with a mean age of 57.1 +/
      14.6 years were studied. All patients complained of intermittent dysphagia for
      solid food and 113 (79.6%) patients had a history of food impaction. Patients
      experienced symptoms for a mean of 4.7 +/- 5.2 years before diagnosis. Only in
      23.4% of the 64 patients who had endoscopic and/or radiological examinations
      before their first presentation to our clinic, was the SR previously diagnosed.
      At presentation, the mean ring diameter was 13.9 +/- 4.97 mm. One hundred and
      sixty-two (97%) patients showed a sliding hiatal hernia. Erosive reflux
      esophagitis was found in 47 (28.1%) patients. Twenty-six (15.6%) of 167 patients
      showed single or multiple esophageal webs; five (3.0%) patients exhibited
      eosinophilic esophagitis; and four (2.4%) had esophageal diverticula. Four (7%)
      of 57 patients undergoing esophageal manometry had non-specific esophageal
      motility disorders. CONCLUSION: Schatzki rings are frequently associated with
      additional esophageal disorders, which support the assumption of a multifactorial
      etiology. Despite typical symptoms, SRs might be overlooked.

PMID- 21734792
TI  - Factors influencing lower esophageal sphincter relaxation after deglutition.
AB  - AIM: To study the relationship between upper esophageal sphincter (UES)
      relaxation, peristaltic pressure and lower esophageal sphincter (LES) relaxation
      following deglutition in non-dysphagic subjects. METHODS: Ten non-dysphagic adult
      subjects had a high-resolution manometry probe passed transnasally and positioned
      to cover the UES, the esophageal body and the LES. Ten water swallows in each
      subject were analyzed for time lag between UES relaxation and LES relaxation, LES
      pressure at time of UES relaxation, duration of LES relaxation, the distance
      between the transition level (TL) and the LES, time in seconds that the
      peristaltic wave was before (negative value) or after the TL when the LES became
      relaxed, and the maximal peristaltic pressure in the body of the esophagus.
      RESULTS: Relaxation of the LES occurred on average 3.5 s after the bolus had
      passed the UES and in most cases when the peristaltic wave front had reached the
      TL. The LES remained relaxed until the peristaltic wave faded away above the LES.
      CONCLUSION: LES relaxation seemed to be caused by the peristaltic wave pushing
      the bolus from behind against the LES gate.

PMID- 21734793
TI  - Effects of sargentgloryvine stem extracts on HepG-2 cells in vitro and in vivo.
AB  - AIM: To observe the effects of sargentgloryvine stem extracts (SSE) on the
      hepatoma cell line HepG-2 in vitro and in vivo and determine its mechanisms of
      action. METHODS: Cultured HepG-2 cells treated with SSE were analysed by 3-(4,5
      Dimethyl-thiazol-2-yl)-2,5-Diphenyltetrazolium bromide and clone formation assay.
      The cell cycle and apoptosis analysis were conducted by flow cytometric, TdT
      Mediated dUTP Nick End Labeling and acridine orange/ethidium bromide staining
      methods, and protein expression was examined by both reverse transcriptase
      polymerase chain reaction and Western blotting. The pathological changes of the
      tumor cells were observed by haematoxylin and eosin staining. Tumor growth
      inhibition and side effects were determined in a xenograft mouse model. RESULTS:
      SSE treatment could not only inhibit HepG-2 cell proliferation in a dose- and
      time-dependent manner but also induce apoptosis and cell cycle arrest at the S
      phase. The number of colonies formed by SSE-treated tumor cells was fewer than
      that of the controls (P < 0.05). SSE induced caspase-dependent apoptosis
      accompanied by a significant decrease in Bcl-xl and Mcl-1 and elevation of Bak
      expression (P < 0.05). Tumor necrosis factor alpha in the xenograft tumor tissue
      and the liver functions of SSE-treated mice showed no significant changes at week
      8 compared with the control group (P > 0.05). Systemic administration of SSE
      could inhibit the HepG-2 xenograft tumor growth with no obvious toxic side
      effects on normal tissues. CONCLUSION: SSE can induce apoptosis of HepG-2 cells
      in vitro and in vivo through decreasing expression of Bcl-xl and Mcl-1 and
      increasing expression of Bax.

PMID- 21734794
TI  - Sonographic features of duodenal lipomas in eight clinicopathologically diagnosed
      patients.
AB  - AIM: To investigate the sonographic features and diagnostic value of endoscopic
      ultrasonography (EUS) for duodenal lipomas (DLs). METHODS: A total of eight
      consecutive patients with DL diagnosed pathologically were included in the study.
      One EUS expert reviewed the ultrasonic images for all lesions, including the
      original layer of the duodenal wall, the echo intensity and the echo homogeneity.
      The size of the lesions and the perifocal structures were also investigated. The
      diagnosis by EUS was compared with the histological results. RESULTS: Using
      routine endoscopy, only one case was correctly diagnosed as DL. Four cases were
      classified as submucosal tumors, and three cases were mistaken for stromal
      tumors. All tumors appeared as round or oval intensive hyperechoic lesions with
      distinct anterior borders that originated from the submucosal layer on EUS.
      Tumors ranged from 8 to 36 mm in size, with an average size of 16 mm. Homogeneous
      echogenicity was seen in all cases except one that had a tubular structure inside
      the tumor. Echo attenuation was observed only in the area behind the tumors in
      five cases, and it was observed both inside and behind the tumors in three cases
      in which the posterior border was obscure or invisible. Seven (87.5%) cases were
      correctly diagnosed as DL, and one (12.5%) was mistaken as Brunner's gland
      adenoma by EUS. Pathologically, all tumors originated from the submucosal layer
      and consisted of mature fat cells without heteromorphism. Among the fat cells,
      there was a small amount of thick-wall vessels infiltrating the lymphocytes, and
      abundant fibrous connective tissues. CONCLUSION: On EUS, DL is featured as an
      intensive homogeneous hyperechoic submucosal lesion with marked echo attenuation
      and without involvement of the mucosa.

PMID- 21734795
TI  - Association between ITGA2 C807T polymorphism and gastric cancer risk.
AB  - AIM: To evaluate the impact of the ITGA2 gene polymorphism on gastric cancer
      risk. METHODS: A hospital-based case-control study was conducted, including 307
      gastric cancer patients and 307 age- and gender-matched control subjects. The
      genotypes were identified by polymerase chain reaction-restriction fragment
      length polymorphism assay. RESULTS: The frequencies of the wild and variant
      genotypes in cases were significantly different from those of controls (P =
      0.019). Compared with individuals with the wild genotype CC, subjects with the
      variant genotypes (CT + TT) had a significantly higher risk of gastric cancer
      (adjusted odds ratio = 1.57, 95% CI = 1.13-2.17, P = 0.007). In stratified
      analyses, the elevated gastric cancer risk was especially evident in older
      individuals aged > 58 years, nonsmokers and rural subjects. Further analyses
      revealed that the variant genotypes were associated with poor tumor
      differentiation and adjacent organ invasion in the sub-analysis of gastric cancer
      patients. CONCLUSION: The ITGA2 gene C807T polymorphism may be associated with an
      increased risk of gastric cancer, differentiation and invasion of gastric cancer.

PMID- 21734796
TI  - Log-normal censored regression model detecting prognostic factors in gastric
      cancer: a study of 3018 cases.
AB  - AIM: To investigate the efficiency of Cox proportional hazard model in detecting
      prognostic factors for gastric cancer. METHODS: We used the log-normal regression
      model to evaluate prognostic factors in gastric cancer and compared it with the
      Cox model. Three thousand and eighteen gastric cancer patients who received a
      gastrectomy between 1980 and 2004 were retrospectively evaluated. Clinic
      pathological factors were included in a log-normal model as well as Cox model.
      The akaike information criterion (AIC) was employed to compare the efficiency of
      both models. Univariate analysis indicated that age at diagnosis, past history,
      cancer location, distant metastasis status, surgical curative degree, combined
      other organ resection, Borrmann type, Lauren's classification, pT stage, total
      dissected nodes and pN stage were prognostic factors in both log-normal and Cox
      models. RESULTS: In the final multivariate model, age at diagnosis, past history,
      surgical curative degree, Borrmann type, Lauren's classification, pT stage, and
      pN stage were significant prognostic factors in both log-normal and Cox models.
      However, cancer location, distant metastasis status, and histology types were
      found to be significant prognostic factors in log-normal results alone. According
      to AIC, the log-normal model performed better than the Cox proportional hazard
      model (AIC value: 2534.72 vs 1693.56). CONCLUSION: It is suggested that the log
      normal regression model can be a useful statistical model to evaluate prognostic
      factors instead of the Cox proportional hazard model.

PMID- 21734797
TI  - Diaphragm disease compared with cryptogenic multifocal ulcerous stenosing
      enteritis.
AB  - As the use of drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs)
      increases, so too do gastrointestinal ulcers, bleeding, perforation and
      obstruction. Diaphragm disease of the small intestine is formed by submucosal
      fibrosis and destruction of lamina muscularis due to chronic ulceration, which
      corresponds to the most severe stage of NSAID enteropathy. It may lead to
      stricture of the small intestine. If such ulcerations and strictures in the small
      intestine are multiple, differential diagnosis is between diaphragm disease and
      cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), because the gross
      findings of diaphragm disease are similar to those of CMUSE. We report a rare
      case of diaphragm disease caused by NSAID. It has been finally confirmed by
      capsule endoscopy and the origin of chronic obscure gastrointestinal bleeding was
      found to be multiple ulcers and strictures in the small intestine. After
      operation, we diagnosed the patient with diaphragm disease rather than CMUSE.

PMID- 21734798
TI  - Time for the world to move beyond the percutaneous endoscopic gastrostomy.
AB  - Percutaneous endoscopic gastrostomy (PEG) is a proven feeding tube, just as the
      nasogastric tube is proven to be able to deliver enteral nutrition. For long-term
      use, both patient and caregiver want neither. What is desired is the LOOPPEG(r)
      3G tube, more secure than the PEG, and less risky to change than the nasogastric
      tube. Future clinical research should focus on this high-comfort low-risk tube.

PMID- 21734799
TI  - How to protect liver graft with nitric oxide.
AB  - Organ preservation and ischemia reperfusion injury associated with liver
      transplantation play an important role in the induction of graft injury. One of
      the earliest events associated with the reperfusion injury is endothelial cell
      dysfunction. It is generally accepted that endothelial nitric oxide synthase (e
      NOS) is cell-protective by mediating vasodilatation, whereas inducible nitric
      oxide synthase mediates liver graft injury after transplantation. We conducted a
      critical review of the literature evaluating the potential applications of
      regulating and promoting e-NOS activity in liver preservation and
      transplantation, showing the most current evidence to support the concept that
      enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate
      graft liver preservation, as well as preventing subsequent graft reperfusion
      injury. This review deals mainly with the beneficial effects of promoting
      "endogenous" pathways for NO generation, via e-NOS inducer drugs in cold
      preservation solution, surgical strategies such as ischemic preconditioning, and
      alternative "exogenous" pathways that focus on the enrichment of cold storage
      liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary
      of the liver physiology and cell signalling mechanisms that account for
      explaining the e-NOS protective effects in liver preservation and
      transplantation.

PMID- 21734800
TI  - Probiotics in hepatology.
AB  - The paper provides a basic review of intestinal microflora and its importance in
      liver diseases. The intestinal microflora has many important functions, above all
      to maintain the microbial barrier against established as well as potential
      pathogens. Furthermore, it influences the motility and perfusion of the
      intestinal wall, stimulates the intestinal immune system and therefore also the
      so-called common mucosal immune system, reducing bacterial translocation and
      producing vitamins. Immune homeostasis at mucosal level results from a controlled
      response to intestinal luminal antigens. In liver cirrhosis, there are many
      changes in its function, mostly an increase in bacterial overgrowth and
      translocation. In this review, probiotics and their indications in hepatology are
      generally discussed. According to recent knowledge, these preparations are
      indicated in clinical practice only for cases of hepatic encephalopathy.
      Probiotics are able to decrease the permeability of the intestinal wall, and
      decrease bacterial translocation and endotoxemia in animal models as well as in
      clinical studies, which is extremely important in the prevention of complications
      of liver cirrhosis and infection after liver transplantation. Probiotics could
      limit oxidative and inflammatory liver damage and, in some situations, improve
      the histological state, and thus non-alcoholic steatohepatitis could be
      considered as another possible indication.

PMID- 21734801
TI  - Molecular biology of pancreatic cancer.
AB  - In spite of continuous research efforts directed at early detection and treatment
      of pancreatic cancer, the outlook for patients affected by the disease remains
      dismal. With most cases still being diagnosed at advanced stages, no improvement
      in survival prognosis is achieved with current diagnostic imaging approaches. In
      the absence of a dominant precancerous condition, several risk factors have been
      identified including family history, chronic pancreatitis, smoking, diabetes
      mellitus, as well as certain genetic disorders such as hereditary pancreatitis,
      cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and
      Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current
      progress in experimental molecular techniques has enabled detailed understanding
      of the molecular processes of pancreatic cancer development. According to the
      latest information, malignant pancreatic transformation involves multiple
      oncogenes and tumor-suppressor genes that are involved in a variety of signaling
      pathways. The most characteristic aberrations (somatic point mutations and
      allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and
      Wnt signaling, and have a key role in transcription and proliferation, as well as
      systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53).
      Understanding of the underlying molecular mechanisms should promote development
      of new methodology for early diagnosis and facilitate improvement in current
      approaches for pancreatic cancer treatment.

PMID- 21734802
TI  - Genomic imbalances in esophageal carcinoma cell lines involve Wnt pathway genes.
AB  - AIM: To identify molecular markers shared across South African esophageal
      squamous cell carcinoma (ESCC) cell lines using cytogenetics, fluorescence in
      situ hybridization (FISH) and single nucleotide polymorphism (SNP) array copy
      number analysis. METHODS: We used conventional cytogenetics, FISH, and multicolor
      FISH to characterize the chromosomal rearrangements of five ESCC cell lines
      established in South Africa. The whole genome copy number profile was established
      from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC
      software. RESULTS: We detected common translocation breakpoints involving
      chromosomes 1p11-12 and 3p11.2, the latter correlated with the deletion, or
      interruption of the EPHA3 gene. The most significant amplifications involved the
      following chromosomal regions and genes: 11q13.3 (CCND1, FGF3, FGF4, FGF19,
      MYEOV), 8q24.21(C-MYC, FAM84B), 11q22.1-q22.3 (BIRC2, BIRC3), 5p15.2 (CTNND2),
      3q11.2-q12.2 (MINA) and 18p11.32 (TYMS, YES1). The significant deletions included
      1p31.2-p31.1 (CTH, GADD45alpha, DIRAS3), 2q22.1 (LRP1B), 3p12.1-p14.2 (FHIT),
      4q22.1-q32.1 (CASP6, SMAD1), 8p23.2-q11.1 (BNIP3L) and 18q21.1-q21.2 (SMAD4,
      DCC). The 3p11.2 translocation breakpoint was shared across four cell lines,
      supporting a role for genes involved at this site, in particular, the EPHA3 gene
      which has previously been reported to be deleted in ESCC. CONCLUSION: The finding
      that a significant number of genes that were amplified (FGF3, FGF4, FGF19, CCND1
      and C-MYC) or deleted (SFRP2 gene) are involved in the Wnt and fibroblast growth
      factor signaling pathways, suggests that these pathways may be activated in these
      cell lines.

PMID- 21734803
TI  - Characterization of a novel rat cholangiocarcinoma cell culture model-CGCCA.
AB  - AIM: To characterize a culture model of rat CCA cells, which were derived from a
      transplantable TTA-induced CCA and designated as Chang Gung CCA (CGCCA). METHODS:
      The CGCCA cells were cultured at in vitro passage 12 times on a culture dish in
      DMEM medium. To measure the doubling time, 10(3) cells were plated in a 96-well
      plate containing the growth medium. The cells were harvested 4 to 10 d after
      seeding, and a standard MTT assay was used to measure the growth. The phenotype
      of CACCA cell and xenograft was determined by immunohistochemical study. We also
      determine the chromosomal alterations of CGCCA, G-banding and spectral
      karyotyping studies were performed. The CGCCA cell line was transplanted into the
      nude mice for examining its tumorigenicity. 2-Deoxy-2-((18)F)fluoro-D-glucose
      (FDG) autoradiography was also performed to evaluate the FDG uptake of the tumor
      xenograft. RESULTS: The doubling time for the CGCCA cell line was 32 h. After
      transplantation into nude mice, FDG autoradiography showed that the tumors formed
      at the cell transplantation site had a latency period of 4-6 wk with high FDG
      uptake excluding necrosis tissue. Moreover, immunohistochemical staining revealed
      prominent cytoplasmic expression of c-erb-B2, CK19, c-Met, COX-II, EGFR, MUC4,
      and a negative expression of K-ras. All data confirmed the phenotypic features of
      the CGCCA cell line coincide with the xenograft mice tumors, indicating cells
      containing the tumorigenicity of CCA originated from CCA. In addition, karyotypic
      banding analysis showed that the diploid (2n) cell status combines with ring and
      giant rod marker chromosomes in these clones; either both types simultaneously
      appeared or only one type of marker chromosome in a pair appeared in a cell. The
      major materials contained in the marker chromosome were primarily identified from
      chromosome 4. CONCLUSION: The current CGCCA cell line may be used as a non-K-ras
      effect CCA model and to obtain information and reveal novel pathways for CCA.
      Further applications regarding tumor markers or therapeutic targeting of CCA
      should be addressed accordingly.

PMID- 21734804
TI  - alpha-fetoprotein involvement during glucocorticoid-induced precocious maturation
      in rat colon.
AB  - AIM: To investigate the role of alpha-fetoprotein (AFP), a cancer-associated
      fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon.
      METHODS: Colons from suckling Sprague-Dawley rats were used in this study.
      Corticosterone acetate at a dose of 100 MUg/g body weight was given to normal
      pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals
      were injected with identical volumes of normal saline. Some rats receiving
      corticosterone 7 d after birth were also treated with mifepristone (RU38486), a
      glucocorticoid cytoplasm receptor antagonist to investigate the effects of
      glucocorticoids (GCs). The morphological changes of the crypt depth and villous
      height of the villous zone in colon were observed as indices of colon maturation.
      Expression levels of AFP in colons were detected by reverse transcriptase
      polymerase chain reaction and Western blotting. To identify the cellular
      localization of AFP in developing rat colons, double-immunofluorescent staining
      was performed using antibodies to specific mesenchymal cell marker and AFP.
      RESULTS: Corticosterone increased the crypt depth and villous height in the colon
      of 8- and 10-d-old rats with hypercorticoidism compared with that in the control
      animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P =
      0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017).
      These increases were accompanied by an increase of AFP expression in both mRNA
      and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in
      control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats
      higher than in control animals, P = 0.023). Increased crypt depth and villous
      height and increased expression of AFP in the colon of rats with
      hypercorticoidism were blocked by mifepristone. Both had positive staining for
      AFP or vimentin, and overlapped in mesenchymal cells at each tested colon.
      CONCLUSION: GCs promote the development of rat colon. AFP appears to be involved,
      in part, in mediating the effects of GCs in the developmental colon.

PMID- 21734805
TI  - Is hyperhomocysteinemia relevant in patients with celiac disease?
AB  - AIM: To investigate whether this might be related to the presence of
      hyperhomocysteinemia. METHODS: From January 1998 to December 2008, we evaluated
      the presence of hyperhomocysteinemia in a series of 165 adult celiac disease (CD)
      patients (138 females and 27 males, mean age 43 years). RESULTS:
      Hyperhomocysteinemia was evident in 32 patients (19.3%), although most of them
      had moderate levels (mean value 25 mcg/ml; range 15-30). Only one patient had a
      history of myocardial infarction (heterozygosis for N5-N10-metil tetrahydrofolate
      reductase mutation). CONCLUSION: The systematic assessment of
      hyperhomocysteinemia seems, at present, unjustified in CD patients.

PMID- 21734806
TI  - Long-term effects of lamivudine treatment in Japanese chronic hepatitis B
      patients.
AB  - AIM: To analyze the association between the emergence of tyrosine-methionine
      asparatate-asparatate (YMDD) mutants (reverse transcription; rtM204I/V) and
      deterioration of liver function during long-term lamivudine treatment of Japanese
      patients with chronic hepatitis B virus (HBV) infection. METHODS: The data of 61
      consecutive Japanese patients with chronic hepatitis B who underwent continuous
      lamivudine treatment for more than 24 mo and had a virological response were
      analyzed. Analysis of YMDD mutants was done by real-time polymerase chain
      reaction with LightCycler probe hybridization assay for up to 90 mo (mean, 50.8
      mo; range, 24-90 mo). RESULTS: A mixed mutant-type (YMDD + tyrosine-isoleucine
      asparatate-asparatate: YIDD or tyrosine-valine-asparatate-asparatate: YVDD) or a
      mutant-type (YIDD or YVDD) were found in 57.4% of 61 patients at 1 year, 78.7% of
      61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at
      4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and
      33.3% of 6 patients at 7 years. Of the 61 patients, 56 (92%) had mixed mutant- or
      a mutant-type. Only 5 (8%) had no mutants at each observation point. Virological
      breakthrough was found in 26 (46.4%) of 56 patients with YMDD mutants, 20 of whom
      had a hepatitis flare-up: the remaining 30 (53.6%) had neither a virological
      breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up
      had a biochemical and virological response after adefovir was added to the
      lamivudine treatment. CONCLUSION: Our results suggest that it is possible to
      continue lamivudine treatment, even after the emergence of YMDD mutants, up to
      the time that the patients develop a hepatitis flare-up.

PMID- 21734807
TI  - Total embolization of the main splenic artery as a supplemental treatment
      modality for hypersplenism.
AB  - AIM: To study the safety and feasibility of total embolization of the main
      splenic artery as a supplemental treatment modality for hypersplenism with
      thrombocytopenia or leukocytopenia accompanying liver cirrhosis. METHODS: Fifteen
      consecutive patients with hypersplenism due to cirrhosis were enrolled in this
      study from January 2006 to June 2010. All patients underwent total embolization
      of the main splenic artery. Clinical symptoms, white blood cell (WBC) and
      platelet (PLT) counts, splenic volume, and complications of the patients were
      recorded. The patients were followed up for 1 and 6 mo, and 1, 2, 3 years,
      respectively, after operation. RESULTS: Total embolization of the main splenic
      artery was technically successful in all patients. Minor complications occurred
      in 13 patients after the procedure, but no major complications were found. The
      WBC and PLT counts were significantly higher and the residual splenic volume was
      significantly lower 1 and 6 mo, and 1, 2, 3 years after the procedure than before
      the procedure (P < 0.01). Moreover, the residual splenic volume increased very
      slowly with the time after embolization. All patients were alive during the
      follow-up period. CONCLUSION: Total embolization of the main splenic artery is a
      safe and feasible procedure and may serve as a supplemental treatment modality
      for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver
      cirrhosis.

PMID- 21734808
TI  - Antitumor activity of mutant bacterial cytosine deaminase gene for colon cancer.
AB  - AIM: To evaluate bacterial cytosine deaminase (bCD) mutant D314A and 5
      fluorocytosine (5-FC) for treatment of colon cancer in a mouse model. METHODS:
      Recombinant lentivirus vectors that contained wild-type bCD gene (bCDwt), and bCD
      mutant D314A gene (bCD-D314A) with green fluorescence protein gene were
      constructed and used to infect human colon carcinoma LoVo cells, to generate
      stable transfected cells, LoVo/null, LoVo/bCDwt or LoVo/bCD-D314A. These were
      injected subcutaneously into Balb/c nude mice to establish xenograft models. Two
      weeks post-LoVo cell inoculation, PBS or 5-FC (500 mg/kg) was administered by
      intraperitoneal (i.p.) injection once daily for 14 d. On the day after LoVo cell
      injection, mice were monitored daily for tumor volume and survival. RESULTS:
      Sequence analyses confirmed the construction of recombinant lentiviral plasmids
      that contained bCDwt or bCD-D314A. The lentiviral vector had high efficacy for
      gene delivery, and RT-PCR showed that bCDwt or bCD-D314A gene was transferred to
      LoVo cells. Among these treatment groups, gene delivery or 5-FC administration
      alone had no effect on tumor growth. However, bCDwt/5-FC or bCD-D314A/5-FC
      treatment inhibited tumor growth and prolonged survival of mice significantly (P
      < 0.05). Importantly, the tumor volume in the bCD-D314A/5-FC-treated group was
      lower than that in the bCDwt/5-FC group (P < 0.05), and bCD-D314A plus 5-FC
      significantly prolonged survival of mice in comparison with bCDwt plus 5-FC (P <
      0.05). CONCLUSION: The bCD mutant D314A enhanced significantly antitumor activity
      in human colon cancer xenograft models, which provides a promising approach for
      human colon carcinoma therapy.

PMID- 21734809
TI  - CD133(+) gallbladder carcinoma cells exhibit self-renewal ability and
      tumorigenicity.
AB  - AIM: To identify cancer stem cells (CSCs) in human gallbladder carcinomas (GBCs).
      METHODS: Primary GBC cells were cultured under serum-free conditions to produce
      floating spheres. The stem-cell properties of the sphere-forming cells, including
      self-renewal, differentiation potential, chemoresistance and tumorigenicity, were
      determined in vitro or in vivo. Cell surface expression of CD133 was investigated
      in primary tumors and in spheroid cells using flow cytometry. The sphere-colony
      formation ability and tumorigenicity of CD133(+) cells were assayed. RESULTS: In
      vitro culture experiments revealed that floating spheroids were generated from
      primary GBC cells, and these sphere-forming cells could generate new progeny
      spheroids in serum-free media. Spheroid cells were differentiated under serum
      containing conditions with downregulation of the stem cell markers Oct-4, Nanog,
      and nestin (P < 0.05). The differentiated cells showed lower spheroid-colony
      formation ability than the original spheroid cells (P < 0.05). Spheroid cells
      were more resistant to chemotherapeutic reagents than the congenetic adherent
      cells (P < 0.05). Flow cytometry showed enriched CD133(+) population in sphere
      forming cells (P < 0.05). CD133(+) cells possessed high colony-formation ability
      than the CD133(-) population (P < 0.01). CD133(+) cells injected into nude mice
      revealed higher tumorigenicity than their antigen-negative counterparts (P <
      0.05). CONCLUSION: CD133 may be a cell surface marker for CSCs in GBC.

PMID- 21734810
TI  - Pseudopneumoperitoneum in chronic intestinal pseudo-obstruction: a case report.
AB  - Chronic intestinal pseudo-obstruction (CIPO) is a rare disease due to a severe
      gastrointestinal motility disorder which may mimic, on both clinical and
      radiological grounds, mechanical obstruction. We report a case of a 26-year-old
      woman who presented to our institution for plain abdominal radiography for
      referred long-lasting constipation with recurrent episodes of abdominal pain and
      distension. At X-ray, performed both in the upright and supine position, an
      isolated air-fluid level was depicted in the left flank, together with a number
      of radiological signs suggestive of pneumoperitoneum. First, subphrenic
      radiolucency could be observed in the upright film. Second, the intestinal wall
      of some jejunal loops appeared to be outlined in the right flank. Third, the
      inferior cardiac border was clearly depicted in the upright film. The patient
      however had no evidence of peritoneal signs but only hypoactive bowel movements.
      Unenhanced multi-detector computed tomography (MDCT) of the abdomen and pelvis
      was therefore performed. MDCT revealed abnormal air-driven distension of the
      small and large bowel, without evidence of extra-luminal air. All radiological
      signs of pneumoperitoneum turned out to be false-positive results. The patient
      was submitted to pan-colonoscopy and to anorectal manometry to rule out
      Hirshprung's disease, and was finally discharged with a diagnosis of CIPO.

PMID- 21734811
TI  - Hepatocellular carcinoma and industrial epidemics.
AB  - Worldwide, the burden of the non viral causes of hepatocellular carcinoma (HCC)
      is usually underestimated. Clearly industrial goods, tobacco, alcohol and
      processed foods are the agents of new epidemics in modern times which far
      outscore the burden of infectious agents on morbidity and mortality. Smoking, a
      dose-related contributing factor for HCC, receives too little attention in
      clinical practice. In France, tobacco, hepatitis B and C virus and alcohol are
      the main risk factors for HCC mortality (33%, 31% and 26%, respectively). In
      developing countries, where tobacco consumption is dramatically increasing, this
      epidemic may soon surpass hepatitis B. Obesity and diabetes are the contributing
      factors too. The role of industrial processed foods in the increase of the
      prevalence of obesity and diabetes cannot be ignored.

PMID- 21734813
TI  - A.N. Kolmogorov's defence of Mendelism.
AB  - In 1939 N.I. Ermolaeva published the results of an experiment which repeated
      parts of Mendel's classical experiments. On the basis of her experiment she
      concluded that Mendel's principle that self-pollination of hybrid plants gave
      rise to segregation proportions 3:1 was false. The great probability theorist
      A.N. Kolmogorov reviewed Ermolaeva's data using a test, now referred to as
      Kolmogorov's, or Kolmogorov-Smirnov, test, which he had proposed in 1933. He
      found, contrary to Ermolaeva, that her results clearly confirmed Mendel's
      principle. This paper shows that there were methodological flaws in Kolmogorov's
      statistical analysis and presents a substantially adjusted approach, which
      confirms his conclusions. Some historical commentary on the Lysenko-era
      background is given, to illuminate the relationship of the disciplines of
      genetics and statistics in the struggle against the prevailing politically
      correct pseudoscience in the Soviet Union. There is a Brazilian connection
      through the person of Th. Dobzhansky.

PMID- 21734812
TI  - Targeted treatment of recurrent platinum-resistant ovarian cancer: current and
      emerging therapies.
AB  - With advances in surgical techniques and chemotherapeutic agents, mortality rates
      from epithelial ovarian cancer (EOC) have slightly decreased over the last 30
      years. However, EOC still ranks as the most deadly gynecologic cancer with an
      overall 5-year survival rate of 45%. Prognosis is especially disappointing for
      women with platinum-resistant disease, where 80% of patients will fail to respond
      to available therapies. Emerging treatment strategies have sub-sequently focused
      on targets which are integral to tumor growth and metastasis. In this review, we
      will focus on those innovative agents currently under investigation in clinical
      trials.

PMID- 21734814
TI  - Mendelian breeding units versus standard sampling strategies: Mitochondrial DNA
      variation in southwest Sardinia.
AB  - We report a sampling strategy based on Mendelian Breeding Units (MBUs),
      representing an interbreeding group of individuals sharing a common gene pool.
      The identification of MBUs is crucial for case-control experimental design in
      association studies. The aim of this work was to evaluate the possible existence
      of bias in terms of genetic variability and haplogroup frequencies in the MBU
      sample, due to severe sample selection. In order to reach this goal, the MBU
      sampling strategy was compared to a standard selection of individuals according
      to their surname and place of birth. We analysed mitochondrial DNA variation
      (first hypervariable segment and coding region) in unrelated healthy subjects
      from two different areas of Sardinia: the area around the town of Cabras and the
      western Campidano area. No statistically significant differences were observed
      when the two sampling methods were compared, indicating that the stringent sample
      selection needed to establish a MBU does not alter original genetic variability
      and haplogroup distribution. Therefore, the MBU sampling strategy can be
      considered a useful tool in association studies of complex traits.

PMID- 21734815
TI  - Three novel alpha-L-iduronidase mutations in 10 unrelated Chinese
      mucopolysaccharidosis type I families.
AB  - Mucopolysaccharidosis type I (MPS I) arises from a deficiency in the alpha-L
      iduronidase (IDUA) enzyme. Although the clinical spectrum in MPS I patients is
      continuous, it was possible to recognize 3 phenotypes reflecting the severity of
      symptoms, viz., the Hurler, Scheie and Hurler/Scheie syndromes. In this study, 10
      unrelated Chinese MPS I families (nine Hurler and one Hurler/Scheie) were
      investigated, and 16 mutant alleles were identified. Three novel mutations in
      IDUA genes, one missense p.R363H (c.1088G > A) and two splice-site mutations
      (c.1190-1G > A and c.792+1G > T), were found. Notably, 45% (nine out of 20) and
      30% (six out of 20) of the mutant alleles in the 10 families studied were c.1190
      1G > A and c.792+1G > T, respectively. The novel missense mutation p.R363H was
      transiently expressed in CHO cells, and showed retention of 2.3% IDUA activity.
      Neither p.W402X nor p.Q70X associated with the Hurler phenotype, or even p.R89Q
      associated with the Scheie phenotype, was found in this group. Finally, it was
      noted that the Chinese MPS I patients proved to be characterized with a unique
      set of IDUA gene mutations, not only entirely different from those encountered
      among Europeans and Americans, but also apparently not even the same as those
      found in other Asian countries.

PMID- 21734816
TI  - RUNX2 mutations in Taiwanese patients with cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant human skeletal disorder
      comprising hypoplastic clavicles, wide cranial sutures, supernumerary teeth,
      short stature, and other skeletal abnormalities. It is known that mutations in
      the human RUNX2 gene mapped at 6p21 are responsible for CCD. We analyzed the
      mutation patterns of the RUNX2 gene by direct sequencing in six Taiwanese index
      cases with typical CCD. One of the patients was a familial case and the others
      were sporadic cases. Sequencing identified four mutations. Three were caused by
      single nucleotide substitutions, which created a nonsense (p.R391X), two were
      missense mutations (p.R190W, p.R225Q), and the forth was a novel mutation
      (c.1119delC), a one-base deletion. Real time quantitative PCR adapted to
      determine copy numbers of the promoter, all exons and the 3'UTR region of the
      RUNX2 gene detected the deletion of a single allele in a sporadic case. The
      results extend the spectrum of RUNX2 mutations in CCD patients and indicate that
      complete deletions of the RUNX2 gene should be considered in those CCD patients
      lacking a point mutation detected by direct sequencing.

PMID- 21734817
TI  - Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase)
      genes.
AB  - Ghrelin coded by the GHRL gene is related to weight-gain, its deactivation
      possibly depending on its hydrolyzation by butyrylcholinesterase (BChE) encoded
      by the BCHE gene, an enzyme already associated with the body mass index (BMI).
      The aim was to search for relationships between SNPs of the GHRL and BCHE genes
      with BChE activity, BMI and obesity in 144 obese and 153 nonobese Euro-Brazilian
      male blood donors. In the obese individuals, a significant association with
      higher BChE activity, in the 72LM+72MM; -116GG genotype class (GHRL and BCHE
      genes, respectively) was noted. No significant differences were found otherwise,
      through comparisons between obese and control individuals, of genotype and allele
      frequencies in SNPs of the GHRL gene (Arg51Gln and Leu72Met), or mean BMI between
      72LL and 72LM+72MM genotypes. Although there appears to be no direct relationship
      between the examined GHRL SNPs and BMI, the association of the 72M SNP with
      higher BChE activity in obese subjects probably points to a regulatory mechanism,
      thereby implying the influence of the GHRL gene on BChE expression, and a
      consequential metabolic role in the complex process of fat utilization.

PMID- 21734818
TI  - Karyotypic conservatism in samples of Characidium cf. zebra (Teleostei,
      Characiformes, Crenuchidae): Physical mapping of ribosomal genes and natural
      triploidy.
AB  - Basic and molecular cytogenetic analyses were performed in specimens of
      Characidium cf. zebra from five collection sites located throughout the Tiete,
      Paranapanema and Paraguay river basins. The diploid number in specimens from all
      samples was 2n = 50 with a karyotype composed of 32 metacentric and 18
      submetacentric chromosomes in both males and females. Constitutive
      heterochromatin was present at the centromeric regions of all chromosomes and
      pair 23, had additional interstitial heterochromatic blocks on its long arms. The
      nucleolar organizer regions (NORs) were located on the long arms of pair 23,
      while the 5S rDNA sites were detected in different chromosomes among the studied
      samples. One specimen from the Alambari river was a natural triploid and had two
      extra chromosomes, resulting in 2n = 77. The remarkable karyotypic similarity
      among the specimens of C. cf. zebra suggests a close evolutionary relationship.
      On the other hand, the distinct patterns of 5S rDNA distribution may be the
      result of gene flow constraints during their evolutionary history.

PMID- 21734819
TI  - Comparative cytogenetic analysis of two grasshopper species of the tribe
      Abracrini (Ommatolampinae, Acrididae).
AB  - The grasshopper species Orthoscapheus rufipes and Eujivarus fusiformis were
      analyzed using several cytogenetic techniques. The karyotype of O. rufipes,
      described here for the first time, had a diploid number of 2n = 23, whereas E.
      fusiformis had a karyotype with 2n = 21. The two species showed the same
      mechanism of sex determination (XO type) but differed in chromosome morphology.
      Pericentromeric blocks of constitutive heterochromatin (CH) were detected in the
      chromosome complement of both species. CMA(3)/DA/DAPI staining revealed CMA(3)
      positive blocks in CH regions in four autosomal bivalents of O. rufipes and in
      two of E. fusiformis. The location of active NORs differed between the two
      species, occurring in bivalents M(6) and S(9) of O. rufipes and M(6) and M(7) of
      E. fusiformsi. The rDNA sites revealed by FISH coincided with the number and
      position of the active NORs detected by AgNO(3) staining. The variability in
      chromosomal markers accounted for the karyotype differentiation observed in the
      tribe Abracrini.

PMID- 21734820
TI  - Intraspecific crosses resulting in the first occurrence of eight and nine B
      chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae).
AB  - B chromosomes are supernumerary elements present in about 15% of eukaryotic
      species and are most frequently heterochromatic, behave parasitically, show a
      transmission rate higher than standard (A) chromosomes, and can provoke harmful
      effects on carriers. In the current work, Prochilodus lineatus individuals
      carrying eight and nine B chromosomes were obtained by induced crossing performed
      involving breeders with different B chromosome numbers in their cells. The high B
      chromosome numbers found in the offspring were recorded for the first time in
      this species. The use of cytogenetic techniques applied in the present study
      revealed that regardless of the increase in number of B chromosomes in the genome
      of these individuals, those elements did not presented active genes, and showed
      their normal heterochromatic characteristic.

PMID- 21734821
TI  - Genetic parameters and relationships between growth traits and scrotal
      circumference measured at different ages in Nellore cattle.
AB  - Records from 106,212 Nellore animals, born between 1998 and 2006, were used to
      estimate (co)variance components and genetic parameters for birth weight (BW),
      average weight gains from birth to weaning (GBW), average weight gains from
      weaning to after yearling (GWAY), weaning hip height (WHH), postweaning hip
      height (PHH) and scrotal circumferences at 9 (SC9), 12 (SC12) and 15 (SC15)
      months of age. (Co)variance components were estimated by an animal model using
      multi-trait analysis. Heritability estimates for BW, GBW, GWAY, WHH, PHH, SC9,
      SC12 and SC15 were 0.31 +/- 0.01; 0.25 +/- 0.02; 0.30 +/- 0.04; 0.51 +/- 0.04;
      0.54 +/- 0.04; 0.39 +/- 0.01; 0.41 +/- 0.01 and 0.44 +/- 0.02, respectively.
      Genetic correlations between growth traits ranged from 0.09 +/- 0.01 to 0.88 +/-
      0.01, thereby implying that, at any age, selection to increase average weight
      gains will also increase stature. Genetic correlations between BW and average
      weight gains with scrotal circumferences were all positive and moderate (0.15 +/-
      0.03 to 0.38 +/- 0.01). On the other hand, positive and low genetic associations
      were estimated between hip height and scrotal circumference at different ages
      (0.09 +/- 0.01 to 0.17 +/- 0.02). The results of this study pointed out that
      selection to larger scrotal circumferences in males will promote changes in
      average weight gains. In order to obtain Nellore cattle with the stature and size
      suitable for the production system, both weight gain and hip height should be
      included in a selection index.

PMID- 21734822
TI  - Oviduct-specific expression of tissue plasminogen activator in laying hens.
AB  - Egg-laying hens are important candidate bioreactors for pharmaceutical protein
      production because of the amenability of their eggs for protein expression. In
      this study, we constructed an oviduct-specific vector containing tissue
      plasminogen activator (tPA) protein and green fluorescent protein (pL
      2.8OVtPAGFP) and assessed its expression in vitro and in vivo. Oviduct epithelial
      and 3T3 cells were cultured and transfected with pL-2.8OVtPAGFP and pEGP-N1
      (control vector), respectively. The pL-2.8OVtPAGFP vector was administered to
      laying hens via a wing vein and their eggs and tissues were examined for tPA
      expression. The oviduct-specific vector pL-2.8OVtPAGFP was expressed only in
      oviduct epithelial cells whereas pEGP-N1 was detected in oviduct epithelial and
      3T3 cells. Western blotting detected a 89 kDa band corresponding to tPA in egg
      white and oviduct epithelial cells, thus confirming expression of the protein.
      The amount of tPAGFP in eggs ranged 9 to 41 ng/mL on the third day after vector
      injection. The tPA expressed in egg white and oviduct epithelial cells showed
      fibrinolytic activity, indicating that the protein was expressed in active form.
      GFP was observed only in oviducts, with no detection in heart, muscle, liver and
      intestine. This is the first study to report the expression of tPA in egg white
      and oviduct epithelial cells using an oviduct-specific vector.

PMID- 21734823
TI  - Cytogenetic characterization of two species of Frieseomelitta Ihering, 1912
      (Hymenoptera, Apidae, Meliponini).
AB  - The cytogenetic analysis of Frieseomelitta dispar and F. francoi revealed the
      chromosome numbers 2n = 30 and n = 15 and a karyotypic formula 2K =
      4M+2M(t)+4A+20A(M). The number of chromosomes observed was consistent with those
      reported for other Frieseomelitta species. The occurrence of the M(t) chromosome
      and other features of the karyotype formulae suggest a close relationship between
      F. dispar, F. francoi and F. varia. Nevertheless, it was possible to
      differentiate the karyotypes of the species by DAPI/CMA(3) staining, which
      revealed GC-rich regions on two chromosome pairs of F. dispar: one acrocentric
      and one pseudoacrocentric. In F. francoi, the same kinds of regions were observed
      on a pair of metacentrics and on a pair of acrocentrics. Our analysis also
      confirmed the chromosome number conservation in Frieseomelitta and suggests that
      infrequent pericentric inversion could constitute a synapomorphy for the group
      including F. dispar, F. francoi, and F. varia.

PMID- 21734824
TI  - Cloning, expression and characterization of alcohol dehydrogenases in the
      silkworm Bombyx mori.
AB  - Alcohol dehydrogenases (ADH) are a class of enzymes that catalyze the reversible
      oxidation of alcohols to corresponding aldehydes or ketones, by using either
      nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide
      phosphate (NADP), as coenzymes. In this study, a short-chain ADH gene was
      identified in Bombyx mori by 5'-RACE PCR. This is the first time the coding
      region of BmADH has been cloned, expressed, purified and then characterized. The
      cDNA fragment encoding the BmADH protein was amplified from a pool of silkworm
      cDNAs by PCR, and then cloned into E. coli expression vector pET-30a(+). The
      recombinant His-tagged BmADH protein was expressed in E. coli BL21 (DE3), and
      then purified by metal chelating affinity chromatography. The soluble recombinant
      BmADH, produced at low-growth temperature, was instrumental in catalyzing the
      ethanol-dependent reduction of NAD(+), thereby indicating ethanol as one of the
      substrates of BmADH.

PMID- 21734825
TI  - Phylogenetic relationships within Chamaecrista sect. Xerocalyx (Leguminosae,
      Caesalpinioideae) inferred from the cpDNA trnE-trnT intergenic spacer and nrDNA
      ITS sequences.
AB  - Chamaecrista belongs to subtribe Cassiinae (Caesalpinioideae), and it comprises
      over 330 species, divided into six sections. The section Xerocalyx has been
      subjected to a profound taxonomic shuffling over the years. Therefore, we
      conducted a phylogenetic analysis using a cpDNA trnE-trnT intergenic spacer and
      nrDNA ITS/5.8S sequences from Cassiinae taxa, in an attempt to elucidate the
      relationships within this section from Chamaecrista. The tree topology was
      congruent between the two data sets studied in which the monophyly of the genus
      Chamaecrista was strongly supported. Our analyses reinforce that new sectional
      boundaries must be defined in the Chamaecrista genus, especially the inclusion of
      sections Caliciopsis and Xerocalyx in sect. Chamaecrista, considered here
      paraphyletic. The section Xerocalyx was strongly supported as monophyletic;
      however, the current data did not show C. ramosa (microphyllous) and C. desvauxii
      (macrophyllous) and their respective varieties in distinct clades, suggesting
      that speciation events are still ongoing in these specimens.

PMID- 21734826
TI  - Towards an optimal sampling strategy for assessing genetic variation within and
      among white clover (Trifolium repens L.) cultivars using AFLP.
AB  - Cost reduction in plant breeding and conservation programs depends largely on
      correctly defining the minimal sample size required for the trustworthy
      assessment of intra- and inter-cultivar genetic variation. White clover, an
      important pasture legume, was chosen for studying this aspect. In clonal plants,
      such as the aforementioned, an appropriate sampling scheme eliminates the
      redundant analysis of identical genotypes. The aim was to define an optimal
      sampling strategy, i.e., the minimum sample size and appropriate sampling scheme
      for white clover cultivars, by using AFLP data (283 loci) from three popular
      types. A grid-based sampling scheme, with an interplant distance of at least 40
      cm, was sufficient to avoid any excess in replicates. Simulations revealed that
      the number of samples substantially influenced genetic diversity parameters. When
      using less than 15 per cultivar, the expected heterozygosity (He) and Shannon
      diversity index (I) were greatly underestimated, whereas with 20, more than 95%
      of total intra-cultivar genetic variation was covered. Based on AMOVA, a 20
      cultivar sample was apparently sufficient to accurately quantify individual
      genetic structuring. The recommended sampling strategy facilitates the efficient
      characterization of diversity in white clover, for both conservation and
      exploitation.

PMID- 21734827
TI  - Chromosome characterization and variability in some Iridaceae from Northeastern
      Brazil.
AB  - The chromosomes of 15 species of Iridaceae of the genera Alophia, Cipura,
      Eleutherine, Neomarica and Trimezia (subfamily Iridoideae) were examined after
      conventional Giemsa staining. The karyotypes of Alophia drummondii (2n = 14+1B,
      28, 42 and 56), Cipura paludosa (2n = 14), C. xanthomelas (2n = 28) and
      Eleutherine bulbosa (2n = 12) were asymmetric; Neomarica candida, N. caerulea, N.
      humilis, N. glauca, N. gracilis, N. northiana and Neomarica sp. (2n = 18); N. cf.
      paradoxa (2n = 28), Trimezia fosteriana (2n = 52), T. martinicensis (2n = 54) and
      T. connata (2n = 82) were all generally symmetric. New diploid numbers of 2n = 56
      for Alophia drummondii, 2n = 18 for N. candida, N. humilis, N. glauca, and N.
      gracilis, 2n = 28 for N. cf. paradoxa, and 2n = 82 for T. connata are reported.
      The karyotypic evolution of the studied species is discussed.

PMID- 21734828
TI  - Genetic differentiation and geographical Relationship of Asian barley landraces
      using SSRs.
AB  - Genetic diversity in 403 morphologically distinct landraces of barley (Hordeum
      vulgare L. subsp. vulgare) originating from seven geographical zones of Asia was
      studied using simple sequence repeat (SSR) markers from regions of medium to high
      recombination in the barley genome. The seven polymorphic SSR markers
      representing each of the chromosomes chosen for the study revealed a high level
      of allelic diversity among the landraces. Genetic richness was highest in those
      from India, followed by Pakistan while it was lowest for Uzbekistan and
      Turkmenistan. Out of the 50 alleles detected, 15 were unique to a geographic
      region. Genetic diversity was highest for landraces from Pakistan (0.70 +/- 0.06)
      and lowest for those from Uzbekistan (0.18 +/- 0.17). Likewise, polymorphic
      information content (PIC) was highest for Pakistan (0.67 +/- 0.06) and lowest for
      Uzbekistan (0.15 +/- 0.17). Diversity among groups was 40% compared to 60% within
      groups. Principal component analysis clustered the barley landraces into three
      groups to predict their domestication patterns. In total 51.58% of the variation
      was explained by the first two principal components of the barley germplasm.
      Pakistan landraces were clustered separately from those of India, Iran, Nepal and
      Iraq, whereas those from Turkmenistan and Uzbekistan were clustered together into
      a separate group.

PMID- 21734829
TI  - cDNA-AFLP analysis of gene expression differences between the flower bud and
      sprout-shoot apical meristem of Angelica sinensis (Oliv.) Diels.
AB  - Angelica sinensis (Oliv.) Diels (Umbelliferae) is a well-known medicinal plant
      mainly distributed in Gansu Province of China. Its local and global demand is
      significant because of its food and medicinal applications. However, the early
      bolting rate of Angelica sinensis (Oliv.) Diels reaches 20%-60%, which seriously
      affects its food and medicinal qualities. Thus, differences in gene expression
      between the flower bud and sprout-shoot apical meristem underwent analysis, by
      means of cDNA-amplified restriction fragment length polymorphism, to better
      understand the flowering mechanism. 64 primer sets, each of which amplified to 60
      transcript-derived fragments (TDFs), were used. Among these TDFs, 26 were
      expressed specifically in the flower bud. After cloning and sequencing, 32
      distinct sequences were obtained from these 26 TDFs, and 25 were found with
      homologous sequences in databases. Confirmation of differential expression of 13
      sequences was obtained by semi-quantitative RT-PCR, their showing higher
      expression levels in flower buds. These homologous sequences encode transposable
      elements, pentatricopeptide repeat-containing proteins, DNA-binding transcription
      factors, zinc finger (B-box type) family proteins, NADP-dependent sorbitol 6
      phosphate dehydrogenase (S6PDH), amongst others.

PMID- 21734830
TI  - Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian
      Helicobacter pylori, and the implications of sequence variation in tyrosine
      phosphorylation motifs on determining the clinical outcome.
AB  - The population of India harbors one of the world's most highly diverse gene
      pools, owing to the influx of successive waves of immigrants over regular periods
      in time. Several phylogenetic studies involving mitochondrial DNA and Y
      chromosomal variation have demonstrated Europeans to have been the first settlers
      in India. Nevertheless, certain controversy exists, due to the support given to
      the thesis that colonization was by the Austro-Asiatic group, prior to the
      Europeans. Thus, the aim was to investigate pre-historic colonization of India by
      anatomically modern humans, using conserved stretches of five amino acid (EPIYA)
      sequences in the cagA gene of Helicobacter pylori. Simultaneously, the existence
      of a pathogenic relationship of tyrosine phosphorylation motifs (TPMs), in 32 H.
      pylori strains isolated from subjects with several forms of gastric diseases, was
      also explored. High resolution sequence analysis of the above described genes was
      performed. The nucleotide sequences obtained were translated into amino acids
      using MEGA (version 4.0) software for EPIYA. An MJ-Network was constructed for
      obtaining TPM haplotypes by using NETWORK (version 4.5) software. The findings of
      the study suggest that Indian H. pylori strains share a common ancestry with
      Europeans. No specific association of haplotypes with the outcome of disease was
      revealed through additional network analysis of TPMs.

PMID- 21734831
TI  - A two-step strategy for the complementation of M. tuberculosis mutants.
AB  - The sequence of Mycobacterium tuberculosis, completed in 1998, facilitated both
      the development of genomic tools, and the creation of a number of mycobacterial
      mutants. These mutants have a wide range of phenotypes, from attenuated to
      hypervirulent strains. These phenotypes must be confirmed, to rule out possible
      secondary mutations that may arise during the generation of mutant strains. This
      may occur during the amplification of target genes or during the generation of
      the mutation, thus constructing a complementation strain, which expresses the
      wild-type copy of the gene in the mutant strain, becomes necessary. In this study
      we have introduced a two-step strategy to construct complementation strains using
      the Ag85 promoter. We have constitutively expressed dosR and have shown dosR
      expression is restored to wild-type level.

PMID- 21734832
TI  - Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in
      mice.
AB  - Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native
      to the east Mediterranean region and west Asia. Also found in tropical countries,
      such as Brazil, where it is popularly known as "erva-cidreira" or "melissa", it
      is widely used in aqueous- or alcoholic-extract form in the treatment of various
      disorders. The aim was to investigate in vivo its antigenotoxicity and
      antimutagenicity, as well as its genotoxic/mutagenic potential through comet and
      micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or
      500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract
      for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS)
      doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or
      mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE
      exerted an antigenotoxic effect on the blood cells of mice treated with the
      alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus
      testing revealed the protector effect of Mo-EE, but only when administered at the
      highest dose. The implication that an ethanolic extract of M. officinalis has
      antigenotoxic/antimutagenic properties is an indication of its medicinal
      relevance.

PMID- 21734833
TI  - Genotoxic potential of Cotinus coggygria Scop. (Anacardiaceae) stem extract in
      vivo.
AB  - The intention was to evaluate the possible in vivo genotoxic potential in
      different cell-types, of a methanol extract obtained from the plant stem of
      Cotinus coggygria Scop., using the sex-linked recessive lethal (or SLRL) test and
      alkaline comet assay. The SLRL test, revealed the genotoxic effect of this
      extract in postmeiotic and premeiotic germ-cell lines. The comet assay was
      carried out on rat liver and bone marrow at 24 and 72 h after intraperitoneal
      administration. For genotoxic evaluation, three concentrations of the extract
      were tested, viz., 500, 1000 and 2000 mg/kg body weight (bw), based on the
      solubility limit of the extract in saline. Comet tail moment and total scores in
      the group treated with 500 mg/kg bw, 24 and 72 h after treatment, were not
      significantly different from the control group, whereas in the groups of animals,
      under the same conditions, but with 1000 and 2000 mg/kg bw of the extract, scores
      were statistically so. A slight decrease in the comet score and tail moment
      observed in all the doses in the 72 h treatment, gave to understand that DNA
      damage induced by Cotinus coggygria extract decreased with time. The results of
      both tests revealed the genotoxic effect of Cotinus coggygria under our
      experimental conditions.

PMID- 21734834
TI  - Alterations in DNA repair gene expression and their possible regulation in rat
      liver regeneration.
AB  - Rapidly proliferating tissue may require enhanced DNA repair capacity in order to
      avoid fixation of promutagenic DNA lesions to mutations. Partial hepatectomy (PH)
      triggers cell proliferation during liver regeneration (LR). However, little is
      known on how DNA repair genes change and how they are regulated at the
      transcriptional level during LR. In the present study, the Rat Genome 230 2.0
      array was used to detect the expression profiles of DNA repair genes during LR,
      and differential expression of selected genes was confirmed by real-time RT-PCR.
      69 DNA repair genes were found to be associated with LR, more than half of which
      distributed in a cluster characterized by a gradual increase at 24-72h and then
      returning to normal. The expression of base excision repair- and transcription
      coupled repair-related genes was enhanced in the early and intermediate phases of
      LR, whereas the expression of genes related to HR, NHEJ and DNA cross-link
      repair, as well as DNA polymerases and related accessory factors, and editing or
      processing nucleases, were mainly enhanced in the intermediate phase. The
      expression changes of genes in DNA damage response were complicated throughout
      the whole LR. Our data also suggest that the expression of most DNA repair genes
      may be regulated by the cell cycle during LR.

PMID- 21734835
TI  - Antiproliferative effects of Tubi-bee propolis in glioblastoma cell lines.
AB  - Propolis is a resin formed by a complex chemical composition of substances that
      bees collect from plants. Since ancient times, propolis has been used in folk
      medicine, due to its biological properties, that include antimicrobial, anti
      inflammatory, antitumoral and immunomodulatory activities. Glioblastoma is the
      most common human brain tumor. Despite the improvements in GBM standard
      treatment, patients' prognosis is still very poor. The aim of this work was to
      evaluate in vitro the Tubi-bee propolis effects on human glioblastoma (U251 and
      U343) and fibroblast (MRC-5) cell lines. Proliferation, clonogenic capacity and
      apoptosis were analyzed after treatment with 1 mg/mL and 2 mg/mL propolis
      concentrations for different time periods. Additionally, glioblastoma cell lines
      were submitted to treatment with propolis combined with temozolomide (TMZ). Data
      showed an antiproliferative effect of tubi-bee propolis against glioblastoma and
      fibroblast cell lines. Combination of propolis with TMZ had a synergic anti
      proliferative effect. Moreover, propolis caused decrease in colony formation in
      glioblastoma cell lines. Propolis treatment had no effects on apoptosis,
      demonstrating a cytostatic action. Further investigations are needed to elucidate
      the molecular mechanism of the antitumor effect of propolis, and the study of its
      individual components may reveal specific molecules with antiproliferative
      capacity.

PMID- 21734836
TI  - Anoxia- and hypoxia-induced expression of LDH-A* in the Amazon Oscar, Astronotus
      crassipinis.
AB  - Adaptation or acclimation to hypoxia occurs via the modulation of physiologically
      relevant genes, such as erythropoietin, transferrin, vascular endothelial growth
      factor, phosphofructokinase and lactate dehydrogenase A. In the present study, we
      have cloned, sequenced and examined the modulation of the LDH-A gene after an
      Amazonian fish species, Astronotus crassipinis (the Oscar), was exposed to
      hypoxia and anoxia. In earlier studies, we have discovered that adults of this
      species are extremely tolerant to hypoxia and anoxia, while the juveniles are
      less tolerant. Exposure of juveniles to acute hypoxia and anoxia resulted in
      increased LDH-A gene expression in skeletal and cardiac muscles. When exposed to
      graded hypoxia juveniles show decreased LDH-A expression. In adults, the levels
      of LDH-A mRNA did not increase in hypoxic or anoxic conditions. Our results
      demonstrate that, when given time for acclimation, fish at different life-stages
      are able to respond differently to survive hypoxic episodes.

PMID- 21734837
TI  - Adaptive evolution of the vertebrate skeletal muscle sodium channel.
AB  - Tetrodotoxin (TTX) is a highly potent neurotoxin that blocks the action potential
      by selectively binding to voltage-gated sodium channels (Na(v)). The skeletal
      muscle Na(v) (Na(v)1.4) channels in most pufferfish species and certain North
      American garter snakes are resistant to TTX, whereas in most mammals they are TTX
      sensitive. It still remains unclear as to whether the difference in this
      sensitivity among the various vertebrate species can be associated with adaptive
      evolution. In this study, we investigated the adaptive evolution of the
      vertebrate Na(v)1.4 channels. By means of the CODEML program of the PAML 4.3
      package, the lineages of both garter snakes and pufferfishes were denoted to be
      under positive selection. The positively selected sites identified in the p-loop
      regions indicated their involvement in Na(v)1.4 channel sensitivity to TTX. Most
      of these sites were located in the intracellular regions of the Na(v)1.4 channel,
      thereby implying the possible association of these regions with the regulation of
      voltage-sensor movement.

PMID- 21734838
TI  - Genetic characterization and phylogeography of the wild boar Sus scrofa
      introduced into Uruguay.
AB  - The European wild boar Sus scrofa was first introduced into Uruguay, in southern
      South America during the early decades of the last century. Subsequently, and
      starting from founder populations, its range spread throughout the country and
      into the neighbouring Brazilian state Rio Grande do Sul. Due to the subsequent
      negative impact, it was officially declared a national pest. The main aim in the
      present study was to provide a more comprehensive scenario of wild boar
      differentiation in Uruguay, by using mtDNA markers to access the genetic
      characterization of populations at present undergoing rapid expansion. A high
      level of haplotype diversity, intermediate levels of nucleotide diversity and
      considerable population differentiation, were detected among sampled localities
      throughout major watercourses and catchment dams countrywide. Phylogenetic
      analysis revealed the existence of two different phylogroups, thereby reflecting
      two deliberate introduction events forming distantly genetic lineages in local
      wild boar populations. Our analysis lends support to the hypothesis that the
      invasive potential of populations emerge from introgressive hybridization with
      domestic pigs. On taking into account the appreciable differentiation and reduced
      migration between locales in wild boar populations, management strategies could
      be effective if each population were to be considered as a single management
      unit.

PMID- 21734839
TI  - Prediction of social structure and genetic relatedness in colonies of the
      facultative polygynous stingless bee Melipona bicolor (Hymenoptera, Apidae).
AB  - Stingless bee colonies typically consist of one single-mated mother queen and her
      worker offspring. The stingless bee Melipona bicolor (Hymenoptera: Apidae) shows
      facultative polygyny, which makes this species particularly suitable for testing
      theoretical expectations concerning social behavior. In this study, we
      investigated the social structure and genetic relatedness among workers from
      eight natural and six manipulated colonies of M. bicolor over a period of one
      year. The populations of M. bicolor contained monogynous and polygynous colonies.
      The estimated genetic relatedness among workers from monogynous and polygynous
      colonies was 0.75 +/- 0.12 and 0.53 +/- 0.16 (mean +/- SEM), respectively.
      Although the parental genotypes had significant effects on genetic relatedness in
      monogynous and polygynous colonies, polygyny markedly decreased the relatedness
      among nestmate workers. Our findings also demonstrate that polygyny in M. bicolor
      may arise from the adoption of related or unrelated queens.

PMID- 21734840
TI  - Isolation and multiplex genotyping of polymorphic microsatellite DNA markers in
      the snakehead murrel, Channa striata.
AB  - Seven polymorphic microsatellite loci were isolated and characterized for the
      snakehead murrel, Channa striata (Channidae), a valuable tropical freshwater fish
      species. Among 25 specimens collected from Kedah state in Malaysia, the number of
      alleles per locus ranged from 2 to 7. Observed and expected heterozygosities
      ranged from 0.120 to 0.880 and 0.117 to 0.698, respectively. A single locus (CS1
      C07) was significantly deviated from Hardy-Weinberg equilibrium after Bonferroni
      correction. These novel markers would be useful for population genetic studies of
      the C. striata.

PMID- 21734841
TI  - Comparative analysis of microsatellite variability in five macaw species
      (Psittaciformes, Psittacidae): Application for conservation.
AB  - Cross-amplification was tested and variability in microsatellite primers
      (designed for Neotropical parrots) compared, in five macaw species, viz., three
      endangered blue macaws (Cyanopsitta spixii [extinct in the wild], Anodorhynchus
      leari [endangered] and Anodorhynchus hyacinthinus [vulnerable]), and two
      unthreatened red macaws (Ara chloropterus and Ara macao). Among the primers
      tested, 84.6% successfully amplified products in C. spixii, 83.3% in A. leari,
      76.4% in A. hyacinthinus, 78.6% in A. chloropterus and 71.4% in A. macao. The
      mean expected heterozygosity estimated for each species, and based on loci
      analyzed in all the five, ranged from 0.33 (A. hyacinthinus) to 0.85 (A. macao).
      As expected, the results revealed lower levels of genetic variability in
      threatened macaw species than in unthreatened. The low combined probability of
      genetic identity and the moderate to high potential for paternity exclusion,
      indicate the utility of the microsatellite loci set selected for each macaw
      species in kinship and population studies, thus constituting an aid in planning
      in-situ and ex-situ conservation.

PMID- 21734842
TI  - Rules extraction from neural networks applied to the prediction and recognition
      of prokaryotic promoters.
AB  - Promoters are DNA sequences located upstream of the gene region and play a
      central role in gene expression. Computational techniques show good accuracy in
      gene prediction but are less successful in predicting promoters, primarily
      because of the high number of false positives that reflect characteristics of the
      promoter sequences. Many machine learning methods have been used to address this
      issue. Neural Networks (NN) have been successfully used in this field because of
      their ability to recognize imprecise and incomplete patterns characteristic of
      promoter sequences. In this paper, NN was used to predict and recognize promoter
      sequences in two data sets: (i) one based on nucleotide sequence information and
      (ii) another based on stability sequence information. The accuracy was
      approximately 80% for simulation (i) and 68% for simulation (ii). In the rules
      extracted, biological consensus motifs were important parts of the NN learning
      process in both simulations.

PMID- 21734844
TI  - From The Editor's Desk.

PMID- 21734845
TI  - Generic drugs: the good, the bad, and the unknown.

PMID- 21734846
TI  - Evaluating safety of handoffs between anesthesia care providers.
AB  - BACKGROUND: Anesthesia care providers frequently exchange care of patients among
      one another. This daily process of information exchange could be a potential
      source for adverse events. OBJECTIVES: Our objectives were to determine if the
      current handoff system is ineffective and if more standardized methods available
      for the exchange of patient information could improve the effectiveness of
      handoffs. METHODS: We distributed a survey to all anesthesia staff, residents,
      and nurse anesthetists. The survey queried the following: handoff adequacy,
      location for best handoff, method for best handoff, and need for inclusion in the
      electronic medical record. RESULTS: We received 80 completed initial surveys from
      anesthesia staff, residents, and nurse anesthetists. Of those surveyed, 20% found
      the existing handoff process inadequate. Most reported both giving and receiving
      a poor or incomplete handoff within the previous year (84% and 57%,
      respectively), and 25% related an adverse outcome to a poor handoff. An
      overwhelming majority, 89%, felt that standardization of this process could
      improve patient care; 68% reported that ideal handoffs would occur in the record,
      as well as in person; and 62% believed that handoffs should be incorporated into
      the electronic medical record. CONCLUSIONS: These data will be used to improve
      the method of the patient care handoff and have assisted us in devising
      techniques that can be incorporated into daily practice, advancing the safety of
      handoffs and decreasing complications. A handoff screen has been included on the
      electronic anesthesia record, encouraging a more formalized procedure for
      handoffs, thereby promoting patient safety.

PMID- 21734847
TI  - Implementation of an Anesthesia Information Management System (AIMS).
AB  - During the administration of anesthesia, the anesthesia provider has historically
      created a paper record, charted manually, that included extensive patient care
      related data (vital signs, other parameters, etc) and commentaries. DocuSys, a
      proprietary anesthesia information management system (AIMS), creates an
      electronic version of the anesthesia record and provides additional information.
      It electronically captures data from clinical monitors and other sources,
      including scheduling applications and laboratory computers. The AIMS facilitates
      chart entries such as drug doses and case narratives. Benefits of an AIMS include
      improved legibility of the anesthesia record and greater efficiency in
      documentation efforts. Use of the AIMS assists the practitioner with decision
      support logic, such as the timing of antibiotic administration and the inclusion
      of legally required documentation. Upon case completion, the AIMS data are
      immediately available to other information systems, such as billing and medical
      records. Data can be made available from a single case or, more important, from
      thousands of cases to analyze variables such as efficiency of services, adherence
      to best practices, patient outcomes, and clinical research. The AIMS was deployed
      at the main campus of the Ochsner Health System on March 26, 2009. In this
      article, we discuss the issues involved in the AIMS implementation process: the
      successes, surprises, and continued challenges.

PMID- 21734848
TI  - Serving in haiti: perspective of a physician.
AB  - In the wake of the 2010 earthquake in Haiti, medical relief organizations and
      individual practitioners mobilized to provide assistance. Here, an emergency
      medicine physician who worked with a Louisiana-based team in the mountains in one
      of the hardest hit areas relates his experiences.

PMID- 21734849
TI  - Medial ectropion repair of lower eyelids with a cicatricial component.
AB  - A new technique for the management of medial ectropion with a mild to moderate
      cicatricial component is presented that avoids the necessity for skin grafting. A
      subciliary incision is made inferior to the punctum and extending laterally,
      followed by preseptal dissection to the orbital rim. A base-up triangle of the
      posterior lamella is then excised lateral to the punctum. This is closed with a
      marginal mattress suture. Tightening of the posterior lamella in this fashion
      produces laxity in the anterior lamella, which can then be closed without
      tension, eliminating the need for skin grafting.

PMID- 21734850
TI  - Atrial ectopic tachycardia in a patient with marfan syndrome.
AB  - The fibrillin defect central to Marfan syndrome is believed to affect myocardial
      conduction and predispose affected patients to various arrhythmias, including
      ventricular tachycardia, atrial fibrillation, and atrioventricular nodal reentry
      tachycardia. Here we describe an adult Marfan patient with atrial ectopic
      tachycardia. To our knowledge, this is the first reported case of atrial ectopic
      tachycardia in the setting of Marfan syndrome.

PMID- 21734851
TI  - Minimally invasive video-assisted thyroidectomy for treatment of benign solitary
      thyroid nodules in pediatric patients.
AB  - OBJECTIVE: To review our experience with minimally invasive video-assisted
      thyroid (MIVAT) surgery for solitary thyroid nodules in the pediatric population.
      STUDY DESIGN: Case series. METHODS: A chart review of pediatric patients with a
      solitary thyroid nodule who underwent a MIVAT procedure from July 2008 to
      December 2009. Eligible patients had a solitary thyroid nodule less than 3.5 cm.
      Endpoints of the study included completion of the procedure, an assessment of
      related complications, and subjective patient satisfaction with respect to
      cosmesis. RESULTS: Two female patients (ages 12 and 17) underwent a MIVAT for
      right-sided solitary thyroid nodules (2.1 cm and 3.3 cm, respectively). Technical
      success was 100% with no conversions to open thyroidectomy. The operative times
      were 180 minutes and 150 minutes, respectively. Pathology was benign in both
      cases (follicular adenoma and nodular hyperplasia, respectively). Neither patient
      had a surgical drain placed, and both were discharged home after a 23-hour
      observation. A postoperative flexible laryngoscopy confirmed bilateral vocal cord
      mobility. There were no major complications, and the patients and parents were
      satisfied with the cosmesis. CONCLUSION: MIVAT is a feasible and safe option for
      the management of solitary thyroid nodules in children.

PMID- 21734852
TI  - Localized myxedema of the foot associated with trauma and surgery.
AB  - Localized extratibial myxedema is a rare presentation of thyroid disease that
      manifests with varied symptoms. Previous surgical or radioiodine treatment of
      hyperthyroidism is linked to the development of localized myxedema, as is prior
      trauma or surgery. We present the first known case of localized foot myxedema on
      a background of Graves disease following a traumatic and surgical precipitant and
      compare and discuss similar cases found in a literature review.

PMID- 21734853
TI  - Closed digital artery injury.
AB  - Closed digital artery injury with secondary acute ischemia is a rare phenomenon.
      The most common injury pattern involves a crush mechanism with a resultant
      transverse fracture in proximity to the interphalangeal joints. Secondary acute
      ischemia requires urgent surgical exploration with digital arterial repair to
      avoid necrosis and associated decreased hand function. One should exercise an air
      of caution when examining significant closed trauma; neurovascular normality
      should be established by an adequately trained physician. We present a case of
      closed digital artery injury with secondary acute ischemia and a review of
      current literature.

PMID- 21734854
TI  - Increase in venous complications associated with etomidate use during a propofol
      shortage: an example of clinically important adverse effects related to drug
      substitution.
AB  - Etomidate is a widely used intravenous induction agent that is especially useful
      for patients at risk for hypotension during anesthesia induction. Side effects
      limiting its use include adrenocortical suppression, acidosis, myoclonus, venous
      irritation, and phlebitis. The osmolality of etomidate prepared in propylene
      glycol appears to play a crucial role in causing phlebitis. The increased use of
      etomidate during the recent propofol shortage correlated with an increase in
      reported incidences of postoperative phlebitis and thrombophlebitis at Ochsner
      Clinic Foundation from October 2009 through April 2010. Several methods aim to
      prevent such occurrences, including pretreatment with lidocaine (and possibly
      esmolol), lower doses of etomidate, and injection into larger veins. The most
      compelling evidence suggests that using a lipid formulation of etomidate instead
      of the traditional propylene glycol preparation may dramatically decrease venous
      sequelae.

PMID- 21734855
TI  - Initial experience with implanted peripheral nerve stimulation for the treatment
      of refractory cephalgia.
AB  - OBJECTIVE: To report 4 cases of improved pain control and function in patients
      with chronic cephalgia secondary to chronic headaches and/or trigeminal
      neuralgia. METHODS: Four patients with refractory cephalgia came to our clinic
      for interventional therapy after medications failure. Each patient underwent a
      trial with a temporary array of peripheral nerve stimulation depending on the
      distribution of their pain. Trials varied in duration from 1 to 3 days. Patients
      who received greater than 50% pain relief during trials were candidates for full
      implantation. All 4 patients went to full implantation of a permanent peripheral
      nerve stimulator lead array and generator battery. RESULTS: After implantation of
      the permanent lead array and generator, average pain relief among the 4 patients
      was 60%. Their function improved, and medication usage decreased along with side
      effects. Overall, all 4 patients reported that they would undergo implantation if
      given the choice again. Tolerance for medication decreases has varied widely,
      although all patients were on regimens that were stable and without side effects.
      CONCLUSIONS: Initial experience suggests that refractory pain secondary to
      chronic migraines and trigeminal neuralgia may respond to peripheral nerve
      stimulation. Further studies are indicated to evaluate efficacy over the long
      term and to elucidate the optimal array and implantation technique.

PMID- 21734856
TI  - Shades of gray: a history of the development of diagnostic ultrasound in a large
      multispecialty clinic.
AB  - The Department of Radiology at the Ochsner Health System has been a central
      player in the development of ultrasound nationally and internationally for much
      of the history of this technology. In the following article, we review the
      progress of ultrasound in our institution.

PMID- 21734857
TI  - Recently published works.

PMID- 21734859
TI  - CME Credit Information.

PMID- 21734858
TI  - Ochsner research update.

PMID- 21734860
TI  - CME Upcoming Events.

PMID- 21734861
TI  - CME Test/CME Application Form.

PMID- 21734862
TI  - Dopamine and effort-based decision making.
AB  - Motivational theories of choice focus on the influence of goal values and
      strength of reinforcement to explain behavior. By contrast relatively little is
      known concerning how the cost of an action, such as effort expended, contributes
      to a decision to act. Effort-based decision making addresses how we make an
      action choice based on an integration of action and goal values. Here we review
      behavioral and neurobiological data regarding the representation of effort as
      action cost, and how this impacts on decision making. Although organisms expend
      effort to obtain a desired reward there is a striking sensitivity to the amount
      of effort required, such that the net preference for an action decreases as
      effort cost increases. We discuss the contribution of the neurotransmitter
      dopamine (DA) toward overcoming response costs and in enhancing an animal's
      motivation toward effortful actions. We also consider the contribution of brain
      structures, including the basal ganglia and anterior cingulate cortex, in the
      internal generation of action involving a translation of reward expectation into
      effortful action.

PMID- 21734863
TI  - Exploring brain function from anatomical connectivity.
AB  - The intrinsic relationship between the architecture of the brain and the range of
      sensory and behavioral phenomena it produces is a relevant question in
      neuroscience. Here, we review recent knowledge gained on the architecture of the
      anatomical connectivity by means of complex network analysis. It has been found
      that cortico-cortical networks display a few prominent characteristics: (i)
      modular organization, (ii) abundant alternative processing paths, and (iii) the
      presence of highly connected hubs. Additionally, we present a novel
      classification of cortical areas of the cat according to the role they play in
      multisensory connectivity. All these properties represent an ideal anatomical
      substrate supporting rich dynamical behaviors, facilitating the capacity of the
      brain to process sensory information of different modalities segregated and to
      integrate them toward a comprehensive perception of the real world. The results
      here exposed are mainly based on anatomical data of cats' brain, but further
      observations suggest that, from worms to humans, the nervous system of all
      animals might share these fundamental principles of organization.

PMID- 21734864
TI  - Impact of synaptic neurotransmitter concentration time course on the kinetics and
      pharmacological modulation of inhibitory synaptic currents.
AB  - The time course of synaptic currents is a crucial determinant of rapid signaling
      between neurons. Traditionally, the mechanisms underlying the shape of synaptic
      signals are classified as pre- and post-synaptic. Over the last two decades, an
      extensive body of evidence indicated that synaptic signals are critically shaped
      by the neurotransmitter time course which encompasses several phenomena including
      pre- and post-synaptic ones. The agonist transient depends on neurotransmitter
      release mechanisms, diffusion within the synaptic cleft, spill-over to the extra
      synaptic space, uptake, and binding to post-synaptic receptors. Most estimates
      indicate that the neurotransmitter transient is very brief, lasting between one
      hundred up to several hundreds of microseconds, implying that post-synaptic
      activation is characterized by a high degree of non-equilibrium. Moreover,
      pharmacological studies provide evidence that the kinetics of agonist transient
      plays a crucial role in setting the susceptibility of synaptic currents to
      modulation by a variety of compounds of physiological or clinical relevance. More
      recently, the role of the neurotransmitter time course has been emphasized by
      studies carried out on brain slice models that revealed a striking, cell
      dependent variability of synaptic agonist waveforms ranging from rapid pulses to
      slow volume transmission. In the present paper we review the advances on studies
      addressing the impact of synaptic neurotransmitter transient on kinetics and
      pharmacological modulation of synaptic currents at inhibitory synapses.

PMID- 21734865
TI  - GABA(A) Receptors: Post-Synaptic Co-Localization and Cross-Talk with Other
      Receptors.
AB  - gamma-Aminobutyric acid type A receptors (GABA(A)Rs) are the major inhibitory
      neurotransmitter receptors in the central nervous system, and importantly
      contribute to the functional regulation of the nervous system. Several studies in
      the last few decades have convincingly shown that GABA can be co-localized with
      other neurotransmitters in the same synapse, and can be co-released with these
      neurotransmitters either from the same vesicles or from different vesicle pools.
      The co-released transmitters may act on post-synaptically co-localized receptors
      resulting in a simultaneous activation of both receptors. Most of the studies
      investigating such co-activation observed a reduced efficacy of GABA for
      activating GABA(A)Rs and thus, a reduced inhibition of the post-synaptic neuron.
      Similarly, in several cases activation of GABA(A)Rs has been reported to suppress
      the response of the associated receptors. Such a receptor cross-talk is either
      mediated via a direct coupling between the two receptors or via the activation of
      intracellular signaling pathways and is used for fine tuning of inhibition in the
      nervous system. Recently, it was demonstrated that a direct interaction of
      different receptors might already occur in intracellular compartments and might
      also be used to specifically target the receptors to the cell membrane. In this
      article, we provide an overview on such cross-talks between GABA(A)Rs and several
      other neurotransmitter receptors and briefly discuss their possible physiological
      and clinical importance.

PMID- 21734866
TI  - Molecular Mechanisms Underlying Cell Death in Spinal Networks in Relation to
      Locomotor Activity After Acute Injury in vitro.
AB  - Understanding the pathophysiological changes triggered by an acute spinal cord
      injury is a primary goal to prevent and treat chronic disability with a mechanism
      based approach. After the primary phase of rapid cell death at the injury site,
      secondary damage occurs via autodestruction of unscathed tissue through complex
      cell-death mechanisms that comprise caspase-dependent and caspase-independent
      pathways. To devise novel neuroprotective strategies to restore locomotion, it
      is, therefore, necessary to focus on the death mechanisms of neurons and glia
      within spinal locomotor networks. To this end, the availability of in vitro
      preparations of the rodent spinal cord capable of expressing locomotor-like
      oscillatory patterns recorded electrophysiologically from motoneuron pools offers
      the novel opportunity to correlate locomotor network function with molecular and
      histological changes long after an acute experimental lesion. Distinct forms of
      damage to the in vitro spinal cord, namely excitotoxic stimulation or severe
      metabolic perturbation (with oxidative stress, hypoxia/aglycemia), can be applied
      with differential outcome in terms of cell types and functional loss. In either
      case, cell death is a delayed phenomenon developing over several hours. Neurons
      are more vulnerable to excitotoxicity and more resistant to metabolic
      perturbation, while the opposite holds true for glia. Neurons mainly die because
      of hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1) with subsequent DNA
      damage and mitochondrial energy collapse. Conversely, glial cells die
      predominantly by apoptosis. It is likely that early neuroprotection against acute
      spinal injury may require tailor-made drugs targeted to specific cell-death
      processes of certain cell types within the locomotor circuitry. Furthermore,
      comparison of network size and function before and after graded injury provides
      an estimate of the minimal network membership to express the locomotor program.

PMID- 21734867
TI  - Projections to early visual areas v1 and v2 in the calcarine fissure from
      parietal association areas in the macaque.
AB  - Non-extrastriate projections to area V1 in monkeys, now demonstrated by several
      anatomical studies, are potential substrates of physiologically documented
      multisensory effects in primary sensory areas. The full network of projections
      among association and primary areas, however, is likely to be complex and is
      still only partially understood. In the present report, we used the anterograde
      tracer biotinylated dextran amine to investigate projections to areas V1 and V2
      from subdivisions of the parietal association cortex in macaque. Parietal cortex
      was chosen to allow comparisons between projections from this higher association
      area and from other previously reported areas. In addition, we were interested in
      further elucidating pathways to areas V1 and V2 from parietal areas, as
      potentially contributing to attention and active vision. Of eight cases, three
      brains had projections only to area V2, and the five others projected to both
      areas V1 and V2. Terminations in area V1 were sparse. These were located in
      supragranular layers I, II, upper III; occasionally in IVB; and in layer VI.
      Terminations in V2 were denser, and slightly more prevalent in the supragranular
      layers. For both areas, terminations were in the calcarine region, corresponding
      to the representation of the peripheral visual field. By reconstructions of
      single axons, we demonstrated that four of nine axons had collaterals, either to
      V1 and V2 (n = 1) or to area V1 and a ventral area likely to be TEO (n = 3). In
      area V1, axons extended divergently in layer VI as well as layer I. Overall,
      these and previous results suggest a nested connectivity architecture, consisting
      of multiple direct and indirect recurrent projections from association areas to
      area V1. Terminations in area V1 are not abundant, but could be potentiated by
      the network of indirect connections.

PMID- 21734868
TI  - Chaotic desynchronization as the therapeutic mechanism of deep brain stimulation.
AB  - High frequency deep-brain stimulation of the subthalamic nucleus (deep brain
      stimulation, DBS) relieves many of the symptoms of Parkinson's disease in humans
      and animal models. Although the treatment has seen widespread use, its
      therapeutic mechanism remains paradoxical. The subthalamic nucleus is excitatory,
      so its stimulation at rates higher than its normal firing rate should worsen the
      disease by increasing subthalamic excitation of the globus pallidus. The
      therapeutic effectiveness of DBS is also frequency and intensity sensitive, and
      the stimulation must be periodic; aperiodic stimulation at the same mean rate is
      ineffective. These requirements are not adequately explained by existing models,
      whether based on firing rate changes or on reduced bursting. Here we report
      modeling studies suggesting that high frequency periodic excitation of the
      subthalamic nucleus may act by desynchronizing the firing of neurons in the
      globus pallidus, rather than by changing the firing rate or pattern of individual
      cells. Globus pallidus neurons are normally desynchronized, but their activity
      becomes correlated in Parkinson's disease. Periodic stimulation may induce
      chaotic desynchronization by interacting with the intrinsic oscillatory mechanism
      of globus pallidus neurons. Our modeling results suggest a mechanism of action of
      DBS and a pathophysiology of Parkinsonism in which synchrony, rather than firing
      rate, is the critical pathological feature.

PMID- 21734869
TI  - Cortical inactivation by cooling in small animals.
AB  - Reversible inactivation of the cortex by surface cooling is a powerful method for
      studying the function of a particular area. Implanted cooling cryoloops have been
      used to study the role of individual cortical areas in auditory processing of
      awake-behaving cats. Cryoloops have also been used in rodents for reversible
      inactivation of the cortex, but recently there has been a concern that the
      cryoloop may also cool non-cortical structures either directly or via the
      perfusion of blood, cooled as it passed close to the cooling loop. In this study
      we have confirmed that the loop can inactivate most of the auditory cortex
      without causing a significant reduction in temperature of the auditory thalamus
      or other subcortical structures. We placed a cryoloop on the surface of the
      guinea pig cortex, cooled it to 2 degrees C and measured thermal gradients across
      the neocortical surface. We found that the temperature dropped to 20-24 degrees C
      among cells within a radius of about 2.5 mm away from the loop. This temperature
      drop was sufficient to reduce activity of most cortical cells and led to the
      inactivation of almost the entire auditory region. When the temperature of
      thalamus, midbrain, and middle ear were measured directly during cortical
      cooling, there was a small drop in temperature (about 4 degrees C) but this was
      not sufficient to directly reduce neural activity. In an effort to visualize the
      extent of neural inactivation we measured the uptake of thallium ions following
      an intravenous injection. This confirmed that there was a large reduction of
      activity across much of the ipsilateral cortex and only a small reduction in
      subcortical structures.

PMID- 21734870
TI  - "What" and "where" in auditory sensory processing: a high-density electrical
      mapping study of distinct neural processes underlying sound object recognition
      and sound localization.
AB  - Functionally distinct dorsal and ventral auditory pathways for sound localization
      (WHERE) and sound object recognition (WHAT) have been described in non-human
      primates. A handful of studies have explored differential processing within these
      streams in humans, with highly inconsistent findings. Stimuli employed have
      included simple tones, noise bursts, and speech sounds, with simulated left-right
      spatial manipulations, and in some cases participants were not required to
      actively discriminate the stimuli. Our contention is that these paradigms were
      not well suited to dissociating processing within the two streams. Our aim here
      was to determine how early in processing we could find evidence for dissociable
      pathways using better titrated WHAT and WHERE task conditions. The use of more
      compelling tasks should allow us to amplify differential processing within the
      dorsal and ventral pathways. We employed high-density electrical mapping using a
      relatively large and environmentally realistic stimulus set (seven animal calls)
      delivered from seven free-field spatial locations; with stimulus configuration
      identical across the "WHERE" and "WHAT" tasks. Topographic analysis revealed
      distinct dorsal and ventral auditory processing networks during the WHERE and
      WHAT tasks with the earliest point of divergence seen during the N1 component of
      the auditory evoked response, beginning at approximately 100 ms. While this
      difference occurred during the N1 timeframe, it was not a simple modulation of N1
      amplitude as it displayed a wholly different topographic distribution to that of
      the N1. Global dissimilarity measures using topographic modulation analysis
      confirmed that this difference between tasks was driven by a shift in the
      underlying generator configuration. Minimum-norm source reconstruction revealed
      distinct activations that corresponded well with activity within putative dorsal
      and ventral auditory structures.

PMID- 21734871
TI  - Glutamate - a forgotten target for interval timing.

PMID- 21734872
TI  - On the Temporary Nature of Disruption of Fear-Potentiated Startle Following
      PKMzeta Inhibition in the Amygdale.

PMID- 21734873
TI  - New perspectives on rodent models of advanced paternal age: relevance to autism.
AB  - Offspring of older fathers have an increased risk of various adverse health
      outcomes, including autism and schizophrenia. With respect to biological
      mechanisms for this association, there are many more germline cell divisions in
      the life history of a sperm relative to that of an oocyte. This leads to more
      opportunities for copy error mutations in germ cells from older fathers. Evidence
      also suggests that epigenetic patterning in the sperm from older men is altered.
      Rodent models provide an experimental platform to examine the association between
      paternal age and brain development. Several rodent models of advanced paternal
      age (APA) have been published with relevance to intermediate phenotypes related
      to autism. All four published APA models vary in key features creating a lack of
      consistency with respect to behavioral phenotypes. A consideration of common
      phenotypes that emerge from these APA-related mouse models may be informative in
      the exploration of the molecular and neurobiological correlates of APA.

PMID- 21734874
TI  - The Specific Outcomes of Reactivation-Induced Memory Changes Depend on the Degree
      of Competition between Old and New Information.

PMID- 21734875
TI  - The role of cannabinoids in modulating emotional and non-emotional memory
      processes in the hippocampus.
AB  - Cannabinoid agonists generally have a disruptive effect on memory, learning, and
      operant behavior that is considered to be hippocampus-dependent. Nevertheless,
      under certain conditions, cannabinoid receptor activation may facilitate neuronal
      learning processes. For example, CB(1) receptors are essential for the extinction
      of conditioned fear associations, indicating an important role for this receptor
      in neuronal emotional learning and memory. This review examines the diverse
      effects of cannabinoids on hippocampal memory and plasticity. It shows how the
      effects of cannabinoid receptor activation may vary depending on the route of
      administration, the nature of the task (aversive or not), and whether it involves
      emotional memory formation (e.g., conditioned fear and extinction learning) or
      non-emotional memory formation (e.g., spatial learning). It also examines the
      memory stage under investigation (acquisition, consolidation, retrieval,
      extinction), and the brain areas involved. Differences between the effects of
      exogenous and endogenous agonists are also discussed. The apparently biphasic
      effects of cannabinoids on anxiety is noted as this implies that the effects of
      cannabinoid receptor agonists on hippocampal learning and memory may be
      attributable to a general modulation of anxiety or stress levels and not to
      memory per se. The review concludes that cannabinoids have diverse effects on
      hippocampal memory and plasticity that cannot be categorized simply into an
      impairing or an enhancing effect. A better understanding of the involvement of
      cannabinoids in memory processes will help determine whether the benefits of the
      clinical use of cannabinoids outweigh the risks of possible memory impairments.

PMID- 21734876
TI  - Perceptual and Physiological Responses to Jackson Pollock's Fractals.
AB  - Fractals have been very successful in quantifying the visual complexity exhibited
      by many natural patterns, and have captured the imagination of scientists and
      artists alike. Our research has shown that the poured patterns of the American
      abstract painter Jackson Pollock are also fractal. This discovery raises an
      intriguing possibility - are the visual characteristics of fractals responsible
      for the long-term appeal of Pollock's work? To address this question, we have
      conducted 10 years of scientific investigation of human response to fractals and
      here we present, for the first time, a review of this research that examines the
      inter-relationship between the various results. The investigations include eye
      tracking, visual preference, skin conductance, and EEG measurement techniques. We
      discuss the artistic implications of the positive perceptual and physiological
      responses to fractal patterns.

PMID- 21734877
TI  - Deciphering elapsed time and predicting action timing from neuronal population
      signals.
AB  - The proper timing of actions is necessary for the survival of animals, whether in
      hunting prey or escaping predators. Researchers in the field of neuroscience have
      begun to explore neuronal signals correlated to behavioral interval timing. Here,
      we attempt to decode the lapse of time from neuronal population signals recorded
      from the frontal cortex of monkeys performing a multiple-interval timing task. We
      designed a Bayesian algorithm that deciphers temporal information hidden in noisy
      signals dispersed within the activity of individual neurons recorded from monkeys
      trained to determine the passage of time before initiating an action. With this
      decoder, we succeeded in estimating the elapsed time with a precision of
      approximately 1 s throughout the relevant behavioral period from firing rates of
      25 neurons in the pre-supplementary motor area. Further, an extended algorithm
      makes it possible to determine the total length of the time-interval required to
      wait in each trial. This enables observers to predict the moment at which the
      subject will take action from the neuronal activity in the brain. A separate
      population analysis reveals that the neuronal ensemble represents the lapse of
      time in a manner scaled relative to the scheduled interval, rather than
      representing it as the real physical time.

PMID- 21734878
TI  - Weight-Based Adaptation of TNF-Antagonist Induction versus Maintenance Dose.
AB  - Biologics are highly specific and exhibit few problems in regard to overdosages.
      In clinical practice, induction schemes with an initial loading dose and a
      subsequent lower maintenance dose have been established and are of higher
      efficacy for psoriasis than starting directly with the maintenance dose. As obese
      patients sometimes respond less well to standard dosages, increases of the
      maintenance dose, but not the loading doses, have been tried with variable
      success. In our study, we increased the loading (160 mg instead of 80 mg) but not
      the maintenance dose of adalimumab in an obese patient with severe psoriasis
      resistant to previous biologics and methotrexate. Within 12 weeks, both PASI (11
      to 1.6) and DLQI (22/30 to 5/30) decreased. This strategy might be an effective
      and less costly alternative to doubling the maintenance doses, and could be
      further evaluated for psoriasis patients refractory to previous treatments.

PMID- 21734879
TI  - Thoracic duct fistula after thyroid cancer surgery: towards a new treatment?
AB  - The use of somatostatin analogs is a new conservative therapeutic approach for
      the treatment of chyle fistulas developing after thyroid cancer surgery. The
      combination therapy with a total parenteral nutrition should avoid the high
      morbidity of a re-intervention with an uncertain outcome. This promising trend is
      supported by the present case report of a chyle leak occurring after total
      thyroidectomy with central and lateral neck dissection for a papillary carcinoma,
      which was treated successfully without immediate or distant sequelae.

PMID- 21734880
TI  - A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus
      Modified FOLFOX6 as the Fourth-Line Chemotherapy.
AB  - High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma,
      and its prognosis is dismal. In this case report, a case of high-grade
      neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as
      the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver
      tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the
      liver. Multiple liver and bone metastases were found one month after surgery. He
      was treated with three chemotherapy regimens used for the management of small
      cell lung cancer with extensive disease. However, none of them could be
      maintained because of tumor progression. He was then treated with bevacizumab
      plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was
      obtained, and a partial response was achieved. This case suggests that high-grade
      neuroendocrine carcinoma can be treated with bevacizumab in combination with
      cytotoxic chemotherapy.

PMID- 21734881
TI  - Primary primitive neuroectodermal tumor of the conus medullaris in an elderly
      patient: a case report and review of the literature.
AB  - Primary spinal primitive neuroectodermal tumors (PNETs) are very rare conditions.
      Most of these tumors occur in children and young adults. A 63-year-old man with a
      primary spinal PNET in the conus medullaris from the L1 to L2 level is presented
      in this report. The optimal treatment of primary spinal PNETs is yet unknown.
      Surgical resection, radiation therapy, and chemotherapy have been advocated for
      the treatment of spinal PNET based on PNETs at other sites. However, the outcome
      is very poor. There are a few reports of cases with long-term survival and no
      recurrence. In these patients, en bloc resections were performed.

PMID- 21734882
TI  - A case report of lipid-rich carcinoma of the breast including histological
      characteristics and intrinsic subtype profile.
AB  - A 57-year-old Japanese woman with schizophrenia, who had received long-term
      treatment with neuroleptics, noticed a painless, pea-sized lump in her right
      breast. She was admitted to our hospital and a malignant tumor was diagnosed. The
      patient underwent a conservative radical mastectomy (Patey's operation). The
      excised tumor measured 2.0 * 1.2 * 1.1 cm in diameter, and its cut surface was
      grayish-white. Histologically, tumor cells with clear to foamy cytoplasm were
      invariably Oil Red O-positive and periodic acid Schiff-negative with or without
      diastase digestion. The tumor was diagnosed as a lipid-rich carcinoma accompanied
      by an in situ component. Neuroleptics increase serum prolactin levels by
      interfering with dopaminergic inhibition of prolactin secretion.
      Immunohistochemical analysis revealed that, although prolactin was not detected,
      the tumor cells expressed prolactin receptor, indicating prolactin as the genesis
      of this neoplasm. In immunohistochemical intrinsic subtype analysis, the tumor
      was negative for estrogen receptor, progesterone receptor, human epidermal growth
      factor receptor 1 and 2, and basal cytokeratins (CK5, CK6, and CK14), indicating
      an unclassified (all-marker negative) subtype. Axillary lymph nodes were free of
      metastasis (stage I), and the patient has been well for 20 years without any
      evidence of recurrence.

PMID- 21734883
TI  - Synchronous breast and rectal cancers in a man.
AB  - Breast cancer in men is relatively rare and its coexistence with other primary
      non-breast cancers exceptional. Here, we report the case of a 50-year-old man who
      presented with symptoms of rectal adenocarcinoma and in whom a synchronous,
      asymptomatic cancer of the left breast was found incidentally at physical
      examination.

PMID- 21734884
TI  - Pulmonary Artery Leiomyosarcoma Diagnosed without Delay.
AB  - A 63-year-old female presented with abnormal lung shadows but had, apart from
      this, few symptoms. Computed tomography (CT) revealed multiple nodules and
      blockage of the pulmonary artery. She was immediately diagnosed with pulmonary
      artery sarcoma based on a careful differential diagnosis and underwent surgery.
      Her tumor was pathologically diagnosed as leiomyosarcoma (i.e. intimal sarcoma).
      Pulmonary artery sarcoma can be easily confounded with thromboembolism in a
      clinical setting and some cases are diagnosed post mortem only. In our case,
      clinical prediction scores (Wells score, Geneva score, and revised Geneva score)
      for the pulmonary embolism showed low probability. Moreover, chest CT showed
      uncommon findings for pulmonary thromboembolism, as the nodules were too big for
      thrombi. Because surgical resection can provide the only hope of long-term
      survival in cases of pulmonary artery sarcoma, clinicians should consider this
      possibility in the differential diagnosis of pulmonary embolism. Clinical
      prediction scores and CT findings might help to reach the correct diagnosis of
      pulmonary artery sarcoma.

PMID- 21734885
TI  - Circulating tumor cells and cardiac metastasis from esophageal cancer: a case
      report.
AB  - We report the case of a 67-year-old man affected by metastatic esophageal cancer.
      The patient developed a symptomatic heart metastasis presenting as mimicking ST
      segment elevation myocardial infarction. Cardiac magnetic resonance imaging (MRI)
      documented the presence of a mass in the apex and septum of the left ventriculum.
      The dissemination of cancer was confirmed by the detection of circulating tumor
      cells (CTCs) in the peripheral blood, measured by the CellSearch System (Veridex,
      LLC, Raritan, N.J., USA). The blood sample drawn at cardiac disease progression
      revealed the presence of 2 CTCs per 7.5 ml of blood. This report highlights the
      potential role of CTCs as markers of metastatic spread.

PMID- 21734886
TI  - Complete Long-Term Remission of an Inflammatory Pseudotumor under Corticosteroid
      Therapy.
AB  - Inflammatory pseudotumors (IPT) form a group of etiologically, histologically,
      and biologically heterogeneous tumefactive lesions that are histologically
      characterized by prominent inflammatory infiltrates. IPT has been described in
      various organs including the lungs, bladder, liver, spleen, heart, and others. It
      may mimic a malignant tumor clinically and radiologically. We report a case of a
      26-year-old woman with an ALK1-negative IPT (7 cm in maximal diameter) mainly
      located in the 12th right back muscles, surrounding a fractured rib.
      Histologically, the tumor consisted of an inflammatory infiltrate composed
      predominantly of diffusely distributed lymphoplasmacytic cells and stromal
      fibroblasts associated with focal obliterative phlebitis. Conservative steroid
      treatment resulted in complete remission and the patient remained disease-free
      for more than 1 year later. To our knowledge this is the first report of IPT
      involving the skeletal back muscle and complete resolution under corticosteroid
      treatment.

PMID- 21734887
TI  - Synchronous presentation of a primary iliac lymph node plasmacytoma and a
      prostate adenocarcinoma.
AB  - Synchronous presentation of primary nodal plasmacytoma and prostate cancer is
      very rare and has not been described in the literature. Here, we report a case of
      a patient with nodal plasmacytoma whose clinical presentation was suggestive of
      metastatic prostate cancer in the setting of recently diagnosed prostate cancer.
      The workup and treatment of both malignancies as well as a possible underlying
      common pathologic mechanism (IL-6 gene mutation) are discussed.

PMID- 21734888
TI  - Lobar Dementia due to Extreme Widening of Virchow-Robin Spaces in One Hemisphere.
AB  - Widened perivascular spaces known as Virchow-Robin spaces (VRS) are often seen on
      MRI and are usually incidental findings. It is unclear if enlarged VRS can be
      associated with neurological deficits. In this report, we describe a case of
      lobar dementia associated with unusual VRS widening in one cerebral hemisphere. A
      77-year-old woman, seen at a memory clinic, presented with progressive cognitive
      decline, left hemianopsia, and mild pyramidal signs on the left side. On MRI,
      unusually wide VRS were visible, predominantly in the right centrum semiovale and
      the right temporo-occipital white matter. The clinical syndrome was consistent
      with the extent and location of the abnormally dilated VRS. The high MR signal in
      white matter bridges between the VRS suggested parenchymal damage, possibly
      representing gliotic white matter. No evidence for another etiology was found on
      cerebral MRI and rCBF SPECT. As a conclusion, enlarged VRS in one cerebral
      hemisphere may be associated with cognitive change and neurological deficits.

PMID- 21734889
TI  - Kaposi's Sarcoma of the Bulbar Conjunctiva in an Immunocompetent Patient.
AB  - Kaposi's sarcoma is an uncommon endothelial malignant tumor, first described by
      Moricz Kaposi in 1872. It is commonly encountered in patients with acquired
      immunodeficiency syndrome (AIDS), immunosuppression or organ transplantation.
      Conjunctival Kaposi's sarcoma is a rare tumor, mostly in patients with AIDS. We
      present a selected case with a superior bulbar conjunctival lesion in a patient
      who is HIV negative and immunocompetent, with an unremarkable general medical
      history. The lesion was surgically excised with no adjunctive treatment, and
      histological examination confirmed the diagnosis. There was no recurrence or
      metastasis 5 years after surgery.

PMID- 21734890
TI  - Analytical and experimental pharmacology, challenges ahead.

PMID- 21734891
TI  - Can [I]-Iodocyanopindolol Label beta(3)-Adrenoceptors in Rat Urinary Bladder?
AB  - beta(3)-Adrenoceptors have been demonstrated to mediate urinary bladder smooth
      muscle relaxation but proof of their expression at the protein level has been
      missing because of lack of suitable antibodies or radioligands. As among various
      available radioligands [(125)I]-iodocyanopindolol ([(125)I]-ICYP) exhibited the
      smallest problems in labeling cloned human beta(3)-adrenoceptors in previous
      studies, we have explored its suitability to label beta(3)-adrenoceptors in rat
      urinary bladder in saturation and competition radioligand binding experiments.
      Rat lung was used as an internal control and exhibited all characteristics
      expected from this tissue with regard to beta1/beta2-adrenoceptor labeling.
      Saturation and competition binding studies with [(125)I]-ICYP in rat bladder
      yielded saturable binding sites with an affinity compatible with beta(3)
      adrenoceptors. In competition experiments various agonists and antagonists
      largely exhibited a profile compatible with a population consisting largely of
      beta(3)-adrenoceptors. However, the binding competition properties of ICI 118,551
      and SR 59,230A were not easily explained by the idea of labeling a homogeneous
      beta(3)-adrenoceptor population but interpretation of the data was limited by a
      high degree of non-specific binding in [(125)I]-ICYP concentrations required to
      label the receptors. We conclude that [(125)I]-ICYP can be used to label tissue
      beta(3)-adrenoceptors but results obtained with this ligand have to be
      interpreted with caution.

PMID- 21734892
TI  - Cross-Sensory Facilitation Reveals Neural Interactions between Visual and Tactile
      Motion in Humans.
AB  - Many recent studies show that the human brain integrates information across the
      different senses and that stimuli of one sensory modality can enhance the
      perception of other modalities. Here we study the processes that mediate cross
      modal facilitation and summation between visual and tactile motion. We find that
      while summation produced a generic, non-specific improvement of thresholds,
      probably reflecting higher-order interaction of decision signals, facilitation
      reveals a strong, direction-specific interaction, which we believe reflects
      sensory interactions. We measured visual and tactile velocity discrimination
      thresholds over a wide range of base velocities and conditions. Thresholds for
      both visual and tactile stimuli showed the characteristic "dipper function," with
      the minimum thresholds occurring at a given "pedestal speed." When visual and
      tactile coherent stimuli were combined (summation condition) the thresholds for
      these multisensory stimuli also showed a "dipper function" with the minimum
      thresholds occurring in a similar range to that for unisensory signals. However,
      the improvement of multisensory thresholds was weak and not directionally
      specific, well predicted by the maximum-likelihood estimation model (agreeing
      with previous research). A different technique (facilitation) did, however,
      reveal direction-specific enhancement. Adding a non-informative "pedestal" motion
      stimulus in one sensory modality (vision or touch) selectively lowered thresholds
      in the other, by the same amount as pedestals in the same modality. Facilitation
      did not occur for neutral stimuli like sounds (that would also have reduced
      temporal uncertainty), nor for motion in opposite direction, even in blocked
      trials where the subjects knew that the motion was in the opposite direction
      showing that the facilitation was not under subject control. Cross-sensory
      facilitation is strong evidence for functionally relevant cross-sensory
      integration at early levels of sensory processing.

PMID- 21734893
TI  - Vision and audition do not share attentional resources in sustained tasks.
AB  - Our perceptual capacities are limited by attentional resources. One important
      question is whether these resources are allocated separately to each sense or
      shared between them. We addressed this issue by asking subjects to perform a
      double task, either in the same modality or in different modalities (vision and
      audition). The primary task was a multiple object-tracking task (Pylyshyn and
      Storm, 1988), in which observers were required to track between 2 and 5 dots for
      4 s. Concurrently, they were required to identify either which out of three
      gratings spaced over the interval differed in contrast or, in the auditory
      version of the same task, which tone differed in frequency relative to the two
      reference tones. The results show that while the concurrent visual contrast
      discrimination reduced tracking ability by about 0.7 d', the concurrent auditory
      task had virtually no effect. This confirms previous reports that vision and
      audition use separate attentional resources, consistent with fMRI findings of
      attentional effects as early as V1 and A1. The results have clear implications
      for effective design of instrumentation and forms of audio-visual communication
      devices.

PMID- 21734894
TI  - Congenital Amusia (or Tone-Deafness) Interferes with Pitch Processing in Tone
      Languages.
AB  - Congenital amusia is a neurogenetic disorder that affects music processing and
      that is ascribed to a deficit in pitch processing. We investigated whether this
      deficit extended to pitch processing in speech, notably the pitch changes used to
      contrast lexical tones in tonal languages. Congenital amusics and matched
      controls, all non-tonal language speakers, were tested for lexical tone
      discrimination in Mandarin Chinese (Experiment 1) and in Thai (Experiment 2).
      Tones were presented in pairs and participants were required to make
      same/different judgments. Experiment 2 additionally included musical analogs of
      Thai tones for comparison. Performance of congenital amusics was inferior to that
      of controls for all materials, suggesting a domain-general pitch-processing
      deficit. The pitch deficit of amusia is thus not limited to music, but may
      compromise the ability to process and learn tonal languages. Combined with
      acoustic analyses of the tone material, the present findings provide new insights
      into the nature of the pitch-processing deficit exhibited by amusics.

PMID- 21734895
TI  - The effect of a music program on phonological awareness in preschoolers.
AB  - The present experiment investigated the effect of a music program on phonological
      awareness in preschoolers. In particular, the effects of a music program and a
      phonological skills program on phonological awareness were compared. If language
      and music share basic processing mechanisms, the effect of both programs on
      enhancing phonological awareness should be similar. Forty-one preschoolers (22
      boys) were randomly assigned to a phonological skills program, a music program,
      and a control group that received sports training (from which no effect was
      expected). Preschoolers were trained for 10 min on a daily basis over a period of
      20 weeks. In a pretest, no differences were found between the three groups in
      regard to age, gender, intelligence, socioeconomic status, and phonological
      awareness. Children in the phonological skills group and the music group showed
      significant increases in phonological awareness from pre- to post-test. The
      children in the sports group did not show a significant increase from pre- to
      post-test. The enhancement of phonological awareness was basically driven by
      positive effects of the music program and the phonological skills program on
      phonological awareness for large phonological units. The data suggests that
      phonological awareness can be trained with a phonological skills program as well
      as a music program. These results can be interpreted as evidence of a shared
      sound category learning mechanism for language and music at preschool age.

PMID- 21734896
TI  - The four postulates of freudian unconscious neurocognitive convergences.
AB  - In the 1980s, the terms "cognitive unconscious" were invented to denominate a
      perspective on unconscious mental processes independent from the psychoanalytical
      views. For several reasons, the two approaches to unconscious are generally
      conceived as irreducible. Nowadays, we are witnessing a certain convergence
      between both fields. The aim of this paper consists in examining the four basic
      postulates of Freudian unconscious at the light of neurocognitive sciences. They
      posit: (1) that some psychological processes are unconsciously performed and
      causally determine conscious processes, (2) that they are governed by their own
      cognitive rules, (3) that they set out their own intentions, (4) and that they
      lead to a conflicting organization of psyche. We show that each of these
      postulates is the subject of empirical and theoretical works. If the two fields
      refer to more or less similar mechanisms, we propose that their opposition rests
      on an epistemological misunderstanding. As a conclusion, we promote a
      conservative reunification of the two perspectives.

PMID- 21734897
TI  - Implications of cognitive load for hypothesis generation and probability
      judgment.
AB  - We tested the predictions of HyGene (Thomas et al., 2008) that both divided
      attention at encoding and judgment should affect the degree to which
      participants' probability judgments violate the principle of additivity. In two
      experiments, we showed that divided attention during judgment leads to an
      increase in subadditivity, suggesting that the comparison process for probability
      judgments is capacity limited. Contrary to the predictions of HyGene, a third
      experiment revealed that divided attention during encoding leads to an increase
      in later probability judgment made under full attention. The effect of divided
      attention during encoding on judgment was completely mediated by the number of
      hypotheses participants generated, indicating that limitations in both encoding
      and recall can cascade into biases in judgments.

PMID- 21734898
TI  - Why pitch sensitivity matters: event-related potential evidence of metric and
      syntactic violation detection among spanish late learners of german.
AB  - Event-related potential (ERP) data in monolingual German speakers have shown that
      sentential metric expectancy violations elicit a biphasic ERP pattern consisting
      of an anterior negativity and a posterior positivity (P600). This pattern is
      comparable to that elicited by syntactic violations. However, proficient French
      late learners of German do not detect violations of metric expectancy in German.
      They also show qualitatively and quantitatively different ERP responses to metric
      and syntactic violations. We followed up the questions whether (1) latter
      evidence results from a potential pitch cue insensitivity in speech segmentation
      in French speakers, or (2) if the result is founded in rhythmic language
      differences. Therefore, we tested Spanish late learners of German, as Spanish,
      contrary to French, uses pitch as a segmentation cue even though the basic
      segmentation unit is the same in French and Spanish (i.e., the syllable). We
      report ERP responses showing that Spanish L2 learners are sensitive to syntactic
      as well as metric violations in German sentences independent of attention to task
      in a P600 response. Overall, the behavioral performance resembles that of German
      native speakers. The current data suggest that Spanish L2 learners are able to
      extract metric units (trochee) in their L2 (German) even though their basic
      segmentation unit in Spanish is the syllable. In addition Spanish in contrast to
      French L2 learners of German are sensitive to syntactic violations indicating a
      tight link between syntactic and metric competence. This finding emphasizes the
      relevant role of metric cues not only in L2 prosodic but also in syntactic
      processing.

PMID- 21734899
TI  - Inhibitory motor control in old age: evidence for de-automatization?
AB  - To examine age-related effects on high-level consciously controlled and low-level
      automatically controlled inhibitory processes, the Simon task was combined with
      the masked prime task in a hybrid procedure. Young and older adults responded to
      the identity of targets (left/right key-press to left-/right-pointing arrows)
      that appeared on the left/right of the screen and were preceded by left-/right
      pointing backward-masked arrow primes at fixation. Responses were faster and more
      accurate when the target was congruent with its location than incongruent (Simon
      effect), and when the target was incompatible with the prime than compatible
      (negative compatibility effect; NCE). The Simon effect was disproportionately
      larger, and the NCE disproportionately delayed, in older adults compared to young
      adults, indicating both high- and low-level inhibitory control deficits with
      aging. Moreover, the two effects were additive in young adults, but interactive
      in older adults, providing support for the dedifferentiation hypothesis of aging.
      Specifically, older adults' prime-related inhibitory control appeared improved on
      incongruent relative to congruent trials, suggesting that impaired automatic
      control was substituted by high-level, non-automatic processes.

PMID- 21734900
TI  - Effects of stimulus type and level repetition on content-level binding in
      global/local processing.
AB  - The processing and representation of hierarchical objects not only involves the
      identification of information at the different levels, but also the binding of
      the identified content to its respective level. Whereas identification is well
      understood, little is known about content-level binding (CLB). In a recent study,
      however, it has been shown that attentional priming of certain spatial
      frequencies is advantageous for this binding. Therefore, the present study
      investigated effects of related factors on the binding process, namely stimulus
      type (filled or outlined hierarchical letters), stimulus-type repetition, and
      target-level repetition. The results show that CLB was improved for outlined
      stimuli and after target-level repetition, whereas stimulus-type repetition had
      no effect. The data suggest that hierarchical stimuli are mentally represented by
      abstract level categories and that content is linked to these categories by means
      of level-specific and identity-specific spatial-frequency information.

PMID- 21734901
TI  - On coding non-contiguous letter combinations.
AB  - Starting from the hypothesis that printed word identification initially involves
      the parallel mapping of visual features onto location-specific letter identities,
      we analyze the type of information that would be involved in optimally mapping
      this location-specific orthographic code onto a location-invariant lexical code.
      We assume that some intermediate level of coding exists between individual
      letters and whole words, and that this involves the representation of letter
      combinations. We then investigate the nature of this intermediate level of coding
      given the constraints of optimality. This intermediate level of coding is
      expected to compress data while retaining as much information as possible about
      word identity. Information conveyed by letters is a function of how much they
      constrain word identity and how visible they are. Optimization of this coding is
      a combination of minimizing resources (using the most compact representations)
      and maximizing information. We show that in a large proportion of cases, non
      contiguous letter sequences contain more information than contiguous sequences,
      while at the same time requiring less precise coding. Moreover, we found that the
      best predictor of human performance in orthographic priming experiments was
      within-word ranking of conditional probabilities, rather than average conditional
      probabilities. We conclude that from an optimality perspective, readers learn to
      select certain contiguous and non-contiguous letter combinations as information
      that provides the best cue to word identity.

PMID- 21734902
TI  - Slowing of mask-triggered inhibition in the elderly.

PMID- 21734903
TI  - Electrophysiological evidence for impaired attentional engagement with
      phonologically acceptable misspellings in developmental dyslexia.
AB  - Event-related potential (ERP) studies of word recognition have provided
      fundamental insights into the time-course and stages of visual and auditory word
      form processing in reading. Here, we used ERPs to track the time-course of
      phonological processing in dyslexic adults and matched controls. Participants
      engaged in semantic judgments of visually presented high-cloze probability
      sentences ending either with (a) their best completion word, (b) a homophone of
      the best completion, (c) a pseudohomophone of the best completion, or (d) an
      unrelated word, to examine the interplay of phonological and orthographic
      processing in reading and the stage(s) of processing affected in developmental
      dyslexia. Early ERP peaks (N1, P2, N2) were modulated in amplitude similarly in
      the two groups of participants. However, dyslexic readers failed to show the P3a
      modulation seen in control participants for unexpected homophones and
      pseudohomophones (i.e., sentence completions that are acceptable phonologically
      but are misspelt). Furthermore, P3a amplitudes significantly correlated with
      reaction times in each experimental condition. Our results showed no sign of a
      deficit in accessing phonological representations during reading, since sentence
      primes yielded phonological priming effects that did not differ between
      participant groups in the early phases of processing. On the other hand, we
      report new evidence for a deficient attentional engagement with orthographically
      unexpected but phonologically expected words in dyslexia, irrespective of task
      focus on orthography or phonology. In our view, this result is consistent with
      deficiency in reading occurring from the point at which attention is oriented to
      phonological analysis, which may underlie broader difficulties in sublexical
      decoding.

PMID- 21734904
TI  - Role of temporal processing stages by inferior temporal neurons in facial
      recognition.
AB  - In this review, we focus on the role of temporal stages of encoded facial
      information in the visual system, which might enable the efficient determination
      of species, identity, and expression. Facial recognition is an important function
      of our brain and is known to be processed in the ventral visual pathway, where
      visual signals are processed through areas V1, V2, V4, and the inferior temporal
      (IT) cortex. In the IT cortex, neurons show selective responses to complex visual
      images such as faces, and at each stage along the pathway the stimulus
      selectivity of the neural responses becomes sharper, particularly in the later
      portion of the responses. In the IT cortex of the monkey, facial information is
      represented by different temporal stages of neural responses, as shown in our
      previous study: the initial transient response of face-responsive neurons
      represents information about global categories, i.e., human vs. monkey vs. simple
      shapes, whilst the later portion of these responses represents information about
      detailed facial categories, i.e., expression and/or identity. This suggests that
      the temporal stages of the neuronal firing pattern play an important role in the
      coding of visual stimuli, including faces. This type of coding may be a plausible
      mechanism underlying the temporal dynamics of recognition, including the process
      of detection/categorization followed by the identification of objects. Recent
      single-unit studies in monkeys have also provided evidence consistent with the
      important role of the temporal stages of encoded facial information. For example,
      view-invariant facial identity information is represented in the response at a
      later period within a region of face-selective neurons. Consistent with these
      findings, temporally modulated neural activity has also been observed in human
      studies. These results suggest a close correlation between the temporal
      processing stages of facial information by IT neurons and the temporal dynamics
      of face recognition.

PMID- 21734905
TI  - Dissecting aneurysms of posterior cerebral artery: clinical presentation,
      angiographic findings, treatment, and outcome.
AB  - BACKGROUND: The dissecting posterior cerebral artery (PCA) aneurysms are very
      rare. These aneurysms pose significant treatment challenge and need careful
      evaluation to formulate an optimal treatment plan in case of ruptured or un
      ruptured presentations. METHODS: Retrospective review of a prospectively
      collected data. RESULTS: Seven patients with dissecting aneurysms of the PCA were
      identified. Six out of seven presented with subarachnoid hemorrhage (SAH) and one
      with ischemic stroke. Three out of seven were treated with endovascular coil
      embolization without sacrifice of the parent artery and the rest had parent
      artery occlusion (PAO) with coil embolization. None of the patients developed new
      neurological deficits post-procedure. Aneurysm re-occurred in two patients that
      were treated without PAO. CONCLUSION: Endovascular treatment of the dissecting
      PCA aneurysm is safe and feasible. It can be performed with or without PAO.
      Recurrence is more common without PAO and close follow-up is warranted.

PMID- 21734906
TI  - The effect of electrical passive cycling on spasticity in war veterans with
      spinal cord injury.
AB  - INTRODUCTION: Muscle atrophy, spasticity, and deformity are among long term
      complication of spinal cord injury (SCI) veterans. There are numerous studies
      evaluating effect of functional electrical stimulation on muscle properties of
      SCI people, but less research has focused on the benefits of passive cycling in
      the management of spasticity and improving ROM of lower limbs in individuals with
      SCI. AIMS: To evaluate the effect of electrical passive cycling on passive range
      of movement spasticity and electrodiagnostic parameters in SCI veterans. METHODS:
      Sixty-four SCI veterans referred to two clinical and research center in Tehran
      were recruited in this prospective clinical trial. The subjects were divided into
      two groups according to electrical passive cycling usage: (1) patients who did
      not use pedal exercise (control group), (2) patients used Electrical passive
      cycling up to optimal level (intervention group). Main outcome measures included
      hip, knee, and ankle range of motion, spasticity scale, and electrodiagnostic
      parameters including F-Wave Consistency, F-Wave Amplitude, H/M Ratio, F/M Ratio,
      H-Reflex Onset Latency, and H-Reflex Amplitude. Data were recorded at the time of
      receiving and 1 year after pedal exercise usage. RESULTS: Sixty-four SCI patients
      including 95.3% male, 4.7% female with mean age 43 years old were included in
      this study. All patients except one suffered from complete SCI. The involved
      spinal levels were cervical (17.2%), upper thoracic (34.4%), lower thoracic
      (45.3%), and lumbar (3.1%). Spasticity scale decreased significantly after
      passive cycling in group 2. Also hip, knee, and ankle ROM in group 2 were
      significantly improved after pedal exercise. There was a significant difference
      in H max/M max (RT&LT) and F/M ratio after versus before electric passive cycling
      system in group 2. CONCLUSION: These findings suggest that passive rhythmic leg
      exercise can lead to decrease in spasticity, increase in passive ROM of lower
      limbs and improvement in electrodiagnostic parameters of spasticity in patients
      with SCI.

PMID- 21734907
TI  - Metabolic flexibility of sulfate-reducing bacteria.
AB  - Dissimilatory sulfate-reducing prokaryotes (SRB) are a very diverse group of
      anaerobic bacteria that are omnipresent in nature and play an imperative role in
      the global cycling of carbon and sulfur. In anoxic marine sediments sulfate
      reduction accounts for up to 50% of the entire organic mineralization in coastal
      and shelf ecosystems where sulfate diffuses several meters deep into the
      sediment. As a consequence, SRB would be expected in the sulfate-containing upper
      sediment layers, whereas methanogenic archaea would be expected to succeed in the
      deeper sulfate-depleted layers of the sediment. Where sediments are high in
      organic matter, sulfate is depleted at shallow sediment depths, and biogenic
      methane production will occur. In the absence of sulfate, many SRB ferment
      organic acids and alcohols, producing hydrogen, acetate, and carbon dioxide, and
      may even rely on hydrogen- and acetate-scavenging methanogens to convert organic
      compounds to methane. SRB can establish two different life styles, and these can
      be termed as sulfidogenic and acetogenic, hydrogenogenic metabolism. The
      advantage of having different metabolic capabilities is that it raises the chance
      of survival in environments when electron acceptors become depleted. In marine
      sediments, SRB and methanogens do not compete but rather complement each other in
      the degradation of organic matter. Also in freshwater ecosystems with sulfate
      concentrations of only 10-200 MUM, sulfate is consumed efficiently within the top
      several cm of the sediments. Here, many of the delta-Proteobacteria present have
      the genetic machinery to perform dissimilatory sulfate reduction, yet they have
      an acetogenic, hydrogenogenic way of life. In this review we evaluate the
      physiology and metabolic mode of SRB in relation with their environment.

PMID- 21734908
TI  - The response of mycobacterium tuberculosis to reactive oxygen and nitrogen
      species.
AB  - The bacteriostatic and bactericidal effects and the transcriptional response of
      Mycobacterium tuberculosis to representative oxidative and nitrosative stresses
      were investigated by growth and survival studies and whole genome expression
      analysis. The M. tuberculosis reaction to a range of hydrogen peroxide (H(2)O(2))
      concentrations fell into three distinct categories: (1) low level exposure
      resulted in induction of a few highly sensitive H(2)O(2)-responsive genes, (2)
      intermediate exposure resulted in massive transcriptional changes without an
      effect on growth or survival, and (3) high exposure resulted in a muted
      transcriptional response and eventual death. M. tuberculosis appears highly
      resistant to DNA damage-dependent, mode-one killing caused by low millimolar
      levels of H(2)O(2) and only succumbs to overwhelming levels of oxidative stress
      observed in mode-two killing. Nitric oxide (NO) exposure initiated much the same
      transcriptional response as H(2)O(2). However, unlike H(2)O(2) exposure, NO
      exposure induced dormancy-related genes and caused dose-dependent bacteriostatic
      activity without killing. Included in the large shared response to H(2)O(2) and
      NO was the induction of genes encoding iron-sulfur cluster repair functions
      including iron acquisition. Stress regulons controlled by IdeR, Sigma H, Sigma E,
      and FurA comprised a large portion of the response to both stresses. Expression
      of several oxidative stress defense genes was constitutive, or increased
      moderately from an already elevated constitutive level, suggesting that bacilli
      are continually primed for oxidative stress defense.

PMID- 21734909
TI  - Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with
      Neisseria gonorrhoeae Strains FA1090 and MS11mkC.
AB  - Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and
      reproduces the clinical features of naturally acquired gonococcal urethritis.
      Human inoculation studies have helped define the natural history of experimental
      infection with two well-characterized strains of N. gonorrhoeae, FA1090 and
      MS11mkC. The human model has proved useful for testing the importance of putative
      gonococcal virulence factors for urethral infection in men. Studies with isogenic
      mutants have improved our understanding of the requirements for gonococcal LOS
      structures, pili, opacity proteins, IgA1 protease, and the ability of infecting
      organisms to obtain iron from human transferrin and lactoferrin during
      uncomplicated urethritis. The model also presents opportunities to examine innate
      host immune responses that may be exploited or improved in development and
      testing of gonococcal vaccines. Here we review results to date with human
      experimental gonorrhea.

PMID- 21734910
TI  - Long term seasonal dynamics of synechococcus population structure in the gulf of
      aqaba, northern red sea.
AB  - Spatial patterns of marine Synechococcus diversity across ocean domains have been
      reported on extensively. However, much less is known of seasonal and multiannual
      patterns of change in Synechococcus community composition. Here we report on the
      genotypic diversity of Synechococcus populations in the Gulf of Aqaba, Northern
      Red Sea, over seven annual cycles of deep mixing and stabile stratification,
      using ntcA as a phylogenetic marker. Synechococcus clone libraries were dominated
      by clade II and XII genotypes and a total of eight different clades were
      identified. Inclusion of ntcA sequences from the Global Ocean Sampling database
      in our analyses identified members of clade XII from beyond the Gulf of Aqaba,
      extending its known distribution. Most of the Synechococcus diversity was
      attributed to members of clade II during the spring bloom, while clade III
      contributed significantly to diversity during summer stratification. Clade XII
      diversity was most prevalent in fall and winter. Clade abundances were estimated
      from pyrosequencing of the V6 hypervariable region of 16S rRNA. Members of clade
      II dominated Synechococcus communities throughout the year, whereas the less
      frequent genotypes showed a pattern of seasonal succession. Based on the
      prevailing nutritional conditions we observed that clade I members thrive at
      higher nutrient concentrations during winter mixing. Clades V, VI and X became
      apparent during the transition periods between mixing and stratification. Clade
      III became prominent during sumeer stratification. We propose that members of
      clades V, VI, and X, and clade III are Synechococcus ecotypes that are adapted to
      intermediate and low nutrient levels respectively. This is the first time that
      molecular analyses have correlated population dynamics of Synechococcus genotypes
      with temporal fluctuations in nutrient regimes. Since these Synechococcus
      genotypes are routinely observed in the Gulf of Aqaba we suggest that seasonal
      fluctuations in nutrient levels create temporal niches that sustain their
      coexistence.

PMID- 21734911
TI  - Cellulitis of the penis: a case report.
AB  - Cellulitis of the penis is an uncommon clinical condition, most often seen in
      young men, and presents with local and systemic signs that progress rapidly in
      the absence of treatment. It needs to be differentiated from sexually transmitted
      infections and dermatological conditions. The present report concerns a case of
      penile cellulitis in a young, heterosexual man, following sexual intercourse. The
      clinical presentation, aetiology and management are discussed. Penile swelling in
      any age group should be viewed with high index of suspicion and sexually
      transmitted infections should be excluded in young men. Group B haemolytic
      streptococci are the usual causative organisms, although less virulent organisms
      should be considered in patients who are immunocompromised. Administration of
      appropriate antibiotics resolves the local and systemic symptoms and avoids
      complications.

PMID- 21734912
TI  - Could it still be malignant melanoma or just a poorly differentiated neoplasm?
AB  - The present case, characterised by an aggressive and poorly differentiated skin
      malignancy, contributes to a wider discussion on such tumours. Despite repeated
      histological examinations, including immunohistochemistry, and thorough
      radiological investigation, diagnosis of melanoma was not easy.

PMID- 21734913
TI  - Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple
      sclerosis.
AB  - Mitoxantrone is an anthracenedione antineoplastic agent approved as an escalating
      immunotherapy for multiple sclerosis. Owing to structural similarity with other
      anthracyclines, cardiotoxicity is a severe side effect of mitoxantrone. The risk
      of mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis
      increases with cumulative doses >100 mg/m(2) body surface area (BSA). However,
      the effect of mitoxantrone on cardiac function in the early phase of treatment
      with cumulative doses <100 mg/m(2) BSA is unclear. The present report concerns
      four patients with a temporary and considerable decrease in left ventricular
      ejection fraction (LVEF) and with additional echocardiographic findings of
      diastolic dysfunction after only one or two doses of mitoxantrone. The risk of
      cardiotoxicity at low doses of mitoxantrone is highlighted.

PMID- 21734914
TI  - Respiratory failure and symptomatic hypercalcaemia complicating pulmonary
      tuberculosis.
AB  - A 47-year-old Caucasian man was admitted to hospital with respiratory failure due
      to a severe pneumonia, requiring admission to the Intensive Care Unit (ICU) for
      respiratory support. Bronchial washings cultured Mycobacterium tuberculosis, a
      rare cause of respiratory failure, and fortunately he responded to standard
      antituberculous therapy. However, the patient subsequently developed symptomatic
      hypercalcaemia; an unusual complication of tuberculosis (TB) in the UK, probably
      contributed to by a combination of sunbathing and activation of 25-hydroxy
      vitamin D in the TB granuloma. The majority of patients treated for TB in the UK
      are probably vitamin D deficient and are therefore unlikely to become
      hypercalcaemic.

PMID- 21734915
TI  - A lightning strike to the head causing a visual cortex defect with simple and
      complex visual hallucinations.
AB  - The case of a 23-year-old mountaineer who was hit by a lightning strike to the
      occiput causing a large central visual field defect and bilateral tympanic
      membrane ruptures is described. Owing to extreme agitation, the patient was sent
      into a drug-induced coma for 3 days. After extubation, she experienced simple and
      complex visual hallucinations for several days, but otherwise largely recovered.
      Neuropsychological tests revealed deficits in fast visual detection tasks and non
      verbal learning and indicated a right temporal lobe dysfunction, consistent with
      a right temporal focus on electroencephalography. At 4 months after the accident,
      she developed a psychological reaction consisting of nightmares, with
      reappearance of the complex visual hallucinations and a depressive syndrome.
      Using the European Cooperation for Lightning Detection network, a meteorological
      system for lightning surveillance, the exact geographical location and nature of
      the lightning strike were retrospectively retraced.

PMID- 21734916
TI  - Hashimoto encephalopathy presenting with progressive cerebellar ataxia.
AB  - Hashimoto encephalopathy has a wide clinical spectrum with various
      neuropsychiatric features. The detection of anti-thyroid antibodies in patient
      sera is helpful, but alone not sufficient for the diagnosis of Hashimoto
      encephalopathy because of the high prevalence of antibodies in the normal
      population. Here, a patient with Hashimoto encephalopathy, who presented with
      progressive cerebellar ataxia with mild abnormality on electroencephalography
      (EEG) and who showed marked improvement after steroid administration, is
      described. This emphasises that Hashimoto encephalopathy can present with
      isolated cerebellar ataxia and is responsive to immunosupression.

PMID- 21734917
TI  - A laparoscopic cholecystectomy with a difference: the case of an incidentally
      detached gallbladder.
AB  - This is the first report of a non-traumatic detached gallbladder noted
      incidentally during an elective laparoscopic cholecystectomy. Gallbladder surgery
      is commonly performed, and many unfamiliar anatomical and pathological findings
      have been reported. Complete disconnection of the gallbladder from the liver bed,
      cystic artery and duct has been previously described following trauma, but to the
      best of the authors' knowledge this is the only published report of non-traumatic
      gallbladder detachment. This report is significant as it presents a previously
      unreported finding that may confront a surgeon during the common surgical
      procedure of laparoscopic cholecystectomy.

PMID- 21734918
TI  - Paroxysmal hemicrania responding to topiramate.
AB  - Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is
      classified along with cluster headache and short-lasting unilateral neuralgiform
      headache attacks with conjunctival injection and tearing (SUNCT) as a trigeminal
      autonomic cephalalgia. CPH is exquisitely responsive to indomethacin, so much so
      that the response is one of the current diagnostic criteria. The case of a
      patient with CPH, who had marked epigastric symptoms with indomethacin treatment
      and responded well to topiramate 150 mg daily, is reported. Cessation of
      topiramate caused return of episodes, and the response has persisted for 2 years.
      Topiramate may be a treatment option in CPH.

PMID- 21734919
TI  - Familial Creutzfeldt-Jakob disease with E200K mutation presenting with
      neurosensorial hypoacusis.
AB  - Creutzfeldt-Jakob disease (CJD) is characterised by rapidly progressive dementia,
      myoclonus, ataxia, visual disturbances and motor dysfunction. Most of the cases
      are sporadic. Only 10% to 15% are familial, and the most frequent point mutation
      is E200K. A 53-year-old man presented with subacute progressive bilateral
      hypoacusis, with tinnitus in the left ear. During the following months, his
      hypoacusis worsened and he progressively developed bilateral stocking-type
      paresthaesia and gait instability. An audiometric examination showed bilateral
      neurosensorial hypoacusis and nerve conduction studies showed a mixed axonal
      polyneuropathy. A CT scan and MRI of the brain were normal and the
      electroencephalography (EEG) showed non-specific changes. He died of respiratory
      infection 10 months after onset of symptoms. Neuropathological examination showed
      neuronal loss, punctate, synaptic-like deposits of protease-resistant prionic
      protein (PrP(RES)) in the cerebral and cerebellar cortices and auditory nuclei.
      This is a rare case of sporadic CJD presenting with hearing loss.

PMID- 21734920
TI  - Flap salvage following postoperative venous thrombosis diagnosed by blood glucose
      measurement in the flaps.
AB  - OBJECTIVE: This is the first paper to report the measurement of blood glucose in
      flaps to detect early flap congestion and flap salvage following immediate flap
      exploration. METHODS: We performed blood glucose measurement in a superficial
      circumflex iliac artery perforator flap and an anterolateral thigh flap
      postoperatively using Medisafe-Mini (Terumo, Japan), a regular capillary blood
      glucose-monitoring device. RESULTS: The blood glucose measurements were low when
      in early venous thrombosis. Low capillary blood glucose levels were detected
      early, even before flap discoloration occurred. CONCLUSIONS: Low capillary blood
      glucose level in congested flaps is an early sign of venous thrombosis. The
      incorporation of blood glucose measurement in addition to clinical monitoring
      aids in early detection and possible reduction postoperative complications due to
      venous thrombosis.

PMID- 21734921
TI  - Daycase urology at Ibadan, Nigeria: a ten year review.
AB  - INTRODUCTION: The objective of the study was to report the extent of urological
      surgeries performed as day cases in a major tertiary hospital in Ibadan and
      document the outcome. METHODS: We retrospectively reviewed the data of all
      urologic patients treated at the day-case theatre between January 2000 and
      December 2009. The parameters evaluated were: age, diagnosis, type of
      surgery/procedure, anaesthesia administered and the rank of the surgeon. Day case
      endoscopic procedures as well as prostate biopsies were excluded from the study.
      RESULTS: In total, 1292 patients were managed, 290 (22.4%) were children aged
      between 5 days and 15 years while 1002 (77.6%) adults aged between 17 years and
      91 years. The majority of the procedures were carried out by the senior
      registrars (1169 cases, 90.5%) and consultants were involved in 123 cases (9.5%).
      General anaesthesia was primarily used in children (158 children vs. 4 adults),
      while local anaesthesia was used only in adults. 131 (45.2%) children had no
      anaesthesia for circumcision. The most common procedures performed in adults were
      varicocelectomy (426 cases, 42.5%), orchidectomy (332 cases, 33.1%), testicular
      biopsy (120 cases, 12.0%). While in children male circumcision (231 cases, 79.7%)
      was the main procedure performed. CONCLUSION: The day-case theatre is still
      suitable for day case urologic procedure in our setting. The common procedures
      are varicocelectomy, orchidectomy, and open testicular biopsy in the adults.
      While in children, male circumcision is commonly carried out.

PMID- 21734922
TI  - Pattern of systemic lupus erythematosus in Egyptian patients: the impact of
      disease activity on the quality of life.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) afflicts young people
      disproportionately, often at a crucial time in their lives when they are trying
      to establish relationships, start families and launch careers. As a result,
      persons with SLE may experience a wide range of physical and psychosocial
      problems that are not always fully captured by descriptions of the disease's
      physiological consequences alone. METHODS: In order to characterize the spectrum
      of the effects of SLE with regards to disease activity and its impact on the
      quality of life (QoL), a case control study involving 59 SLE Egyptian patients
      (mean age 28.6 years, 94.9% females) and 20 healthy controls was undertaken.
      Disease activity was measured by SLE Disease Activity Index (SLEDAI), and quality
      of life was measured by Short Form-36 health questionnaire (SF-36). RESULTS:
      Mucocutaneous and hematological manifestations were present in most of the
      patients and arthralgia in half of them. All domains of SF-36 including general
      health, physical functions, physical limitations, energy/fatigue, emotional well
      being, pain, social functions, and health changes were significantly lower in SLE
      patients compared to controls. Except for emotional limitations, all domains were
      correlated with disease activity and low in class IV-V lupus nephritis.
      CONCLUSION: Physicians should focus on QoL and how to improve it; health
      education regarding the negative impact of disease activity on the patients
      should be given attention. The results of QoL studies help physicians to
      understand and provide better support to SLE patients beside rapid meticulous
      control of disease activity.

PMID- 21734923
TI  - [Peripheral primitive neuroectodermal tumor with gastric primary location: about
      a new case].

PMID- 21734924
TI  - [Management of suicide by fall in traumatology].

PMID- 21734925
TI  - Prevalence of Helicobacter pylori among Nigerian patients with dyspepsia in
      Ibadan.
AB  - INTRODUCTION: Determination of the true prevalence of Helicobacter pylori (H.
      pylori) is difficult in a hyper-endemic area like Nigeria with use of serological
      tests because of their low discriminatory power between previous and current
      infections. The use of biopsy based methods will go a long way to mitigate this
      problem. We investigated the prevalence of H. pylori in dyspeptic patients and
      its relationship with gastroduodenal pathologies using gastric biopsy histology
      and rapid urease test. METHODS: Eighty-six consecutive adult patients with
      dyspepsia underwent upper gastrointestinal endoscopy using forward-viewing
      endoscopes. Antral biopsy specimens were collected for histology and rapid urease
      test. Diagnosis of H. pylori infection was made if both or either of the tests
      was positive. RESULTS: Of the 86 subjects, there were 39 (45.3%) males and 47
      (54.7%) females. The age range was 23 to 85 years with a mean of 49.19+/-13.75
      years. Diagnosis of H. pylori was made in 55 (64%) patients. Gastritis was the
      commonest endoscopic finding (60.5%), serious gastroduodenal pathology (gastric
      ulcer, duodenal ulcer and gastric cancer) were documented in only 12 (14%)
      patients. Thirty three (63.5%) of the 55 patients with gastritis had H. pylori
      infection while 7 (58.3%) of the 12 patients with serious gastroduodenal lesions
      had the infection. Thirteen (72.2%) of the 18 patients that had normal endoscopic
      findings were H. pylori positive. CONCLUSION: The prevalence of H. pylori among
      dyspeptics using biopsy based methods is high in the South-Western part of
      Nigeria. It is therefore important to test and treat H. pylori among Nigerians
      with dyspepsia.

PMID- 21734926
TI  - [Gastric trichobezoar--about two cases].

PMID- 21734927
TI  - [Myocardial infarction in the young adult--retrospective analysis of cases
      compile at the University Hospital of Dakar].

PMID- 21734928
TI  - Cost challenges for laboratory medicine automation in Africa.
AB  - Automation in laboratory medicine is inevitable and the only way forward
      especially in Africa where the staff turnover is high due to migration of
      experienced staff to Europe and America. Described here are the common issues
      that laboratory Managers and Directors encounter when upgrading, replacing
      analytical systems as well as daily running of diagnostic laboratories. The rapid
      advancement driven by the first world where research facilities, resources and
      expertise are available has seen changes in the both the hardware and software
      utilised by analyzers every two to three years. The downside is that in the
      process of replacing/phasing out old analysers, the first world countries in some
      cases donate them to second and third world countries as refurbished analysers.
      Problems in obtaining spares ensue since the production of new analysers results
      in reduced production or even of old spares. Unavailability or delayed
      availability of spares results in suspension of diagnostic service by the
      recipient laboratory. In some areas costly modifications to the analysers or the
      location/building have had to done to suite local (African) conditions, hence the
      need for Laboratory managers to understand fully the analysers' operational
      requirements before purchasing or accepting donations.

PMID- 21734929
TI  - Venous thromboembolism in patients with blunt trauma: are comprehensive
      guidelines the answer?
AB  - OBJECTIVES: This study was designed to determine the outcome of implemented
      guidelines for venous thromboembolism (VTE) prophylaxis. METHODS: This study was
      a retrospective review of a series of consecutive blunt orthopaedic trauma
      patients with thromboembolic complications. The patients were compared to control
      subjects over the same 10-year period. Univariate and multivariate statistical
      methods were used to determine the odds of VTE in the setting of this management
      guideline and risk factors for thromboembolic complications that may be
      refractory to this strategy. RESULTS: In the 10 years following institution of
      clinical management guidelines at our institution, the rate of VTE events was
      3.2%, and the rate of pulmonary embolus was 0.3%. Risk factors for VTE that were
      refractory to our clinical management guidelines were pelvic fractures, major
      lower extremity injury, greater than 3 days of mechanical ventilation, increasing
      injury severity, and spinal cord injury. CONCLUSIONS: The implementation of a
      clinical management strategy for decreasing the incidence of VTE in blunt trauma
      patients and other potentially preventable complications is essential. Our data
      suggest that patients with certain injuries are particularly at risk for VTE and
      warrant special attention in clinical management and risk stratification, despite
      effective clinical management guidelines.

PMID- 21734930
TI  - Arthroscopic pathology or normal variant.

PMID- 21734931
TI  - Acute femoral "peel-off" tears of the posterior cruciate ligament: technique for
      arthroscopic anatomical repair.
AB  - Management of posterior cruciate ligament injuries remains a topic of discussion
      among treating physicians. Injury severity, anatomical location, and presence of
      concomitant associated knee injuries are important factors that may be used to
      guide treatment strategies. Various subtypes of posterior cruciate ligament
      injury have been identified. Each has unique properties that affect treatment
      design. Among these subtypes is the acute femoral "peel-off" tear, which
      represents a distinct pattern of injury that consistently has demonstrated a
      favorable capacity for healing with repair rather than reconstruction. In this
      article, we present an arthroscopic anatomical repair technique that has been
      used with success at our institution. It is important to properly identify such
      injuries in a timely manner so that appropriate treatment is initiated and the
      patient may be spared a lengthier and more technically complex reconstruction
      procedure.

PMID- 21734932
TI  - Oblique radiographs compared favorably with computed tomography images in
      assessing cervical foraminal area.
AB  - Oblique radiographs are often ordered to evaluate the patency of cervical
      intervertebral foramina. Previous studies have shown that computed tomography
      (CT) provides accurate measurements of foraminal dimensions. Up until now, no
      study has directly compared the diagnostic utility of oblique radiographs and CT.
      We conducted a study to quantify the correlation between cervical foramina
      dimensions measured on oblique radiographs and on CT scans. Heights, widths, and
      cross-sectional areas were evaluated at every level from C2-C3 through C7-T1
      using both oblique radiographs and oblique CT reconstructions. Both measurements
      were performed at a 50% oblique angle. Interreliability and intrareliability
      statistics for radiographs and CT were 0.91 and 0.99 for height, 0.90 and 0.97
      for width, and 0.84 and 0.92 for area. Pearson correlation coefficients for
      height, width, and area were 0.439, 0.871, and 0.899, respectively. Oblique
      radiographs of the cervical spine provide accurate estimates of intervertebral
      foraminal dimensions--estimates similar to those generated from CT
      reconstructions. Thus, these radiographs may serve as an acceptable first-line
      imaging study for initial assessment of patients suspected of having nerve root
      compression that precludes the higher cost and radiation exposure associated with
      CT scans.

PMID- 21734933
TI  - Surgical complications associated with extensive tumoral calcinosis.
AB  - In this article, we describe the presenting features, radiographic appearance,
      and proposed pathogenesis of tumoral calcinosis; highlight the surgical
      complications we have encountered with the syndrome; and review the complications
      reported in the literature.

PMID- 21734934
TI  - Synovial chondromatosis of the elbow causing a mechanical block to range of
      motion: a case report and review of the literature.
AB  - We report a unique case of elbow synovial chondromatosis with sudden onset of
      severe loss of elbow extension and flexion range of motion caused by mechanical
      block from deposition of chondral fragments in the olecranon and coronoid fossae,
      respectively. We performed successful arthroscopic surgical treatment of synovial
      chondromatosis of the elbow. Arthroscopy examination revealed an acutely evolving
      synovial chondromatosis. Three-year follow-up indicated that arthroscopic removal
      of loose bodies and partial synovectomy can yield lasting improvement in motion
      without disease recurrence.

PMID- 21734935
TI  - Ganglion cysts of the posterior cruciate ligament.

PMID- 21734936
TI  - Worker's compensation: how do orthopedic surgeons fare?
AB  - INTRODUCTION: Negotiable reimbursement for patients with Workers' Compensation
      (WC) has not been investigated previously. Our study investigated characteristics
      of the revenues (to individual surgeons) associated with these WC patients.
      METHODOLOGY: Patients with WC seen in our orthopedics department from March 1,
      2007 through June 30, 2008 were included. The revenue yield (final payment as
      percentage of original charge billed) and the total time to payment (time to
      process bill plus time for payment) were compared according to visit type,
      subspecialty, insurance payor, and number of Current Procedural Terminology (CPT)
      codes per encounter. RESULTS: Clinic visits (n = 816) comprised 65% of total
      patient encounters, and procedural encounters comprised 35% (n = 436). The
      overall revenue yield for WC was 49%, compared with 31% for Medicare. Yields for
      spine procedures (37%) were significantly lower than for other subspecialties,
      which ranged from 54% to 64% (P = .002). Time to payment was higher for
      procedures than clinic visits (101 vs 63 days, P<.0001), primarily due to
      increased time to post charges. Finally, increased time to payment was associated
      with increasing number of CPT codes per encounter. CONCLUSION: Negotiated
      revenues from WC are greater than from Medicare but vary according to
      subspecialty and payor (with spine having the lowest yield). Time to payment
      displays considerable variation as well, especially in time to post charges.

PMID- 21734937
TI  - An evaluation of brachytherapy and external beam radiation used with wide-margin
      surgical resection in the treatment of extra-abdominal desmoid tumors.
AB  - Surgical resection has had control rates of 53% to 77% in the treatment of extra
      abdominal desmoid tumors. Surgical excision combined with external beam radiation
      therapy (EBRT) has had local control rates of up to 83% in some series. The
      purpose of this study was to evaluate the effectiveness of resection combined
      with radiotherapy (brachytherapy, EBRT, or both) in the treatment of extra
      abdominal desmoid tumors. We retrospectively reviewed the charts of 24
      consecutive patients (27 histologically confirmed extra-abdominal desmoid
      tumors). Patients were included in the study if they had a lesion that was
      potentially resectable with a wide margin, allowing for limb salvage, and if they
      did not have a contraindication to radiotherapy. Limb functioning was assessed
      with the Musculoskeletal Tumor Society (MSTS) scoring system. Seventeen patients
      (7 men, 10 women) with 19 tumors met the inclusion criteria. Mean age at
      diagnosis was 23.4 years. Follow-up (mean, 4.28 years) involved serial clinical
      examinations and magnetic resonance imaging of tumor sites. After surgery, the
      tumors were treated with brachytherapy (n = 6), EBRT (n = 10), or both (n = 3).
      Two of the 17 tumors in patients with negative margins of resection recurred
      locally (local control rate, 88.2%). Mean MSTS score was 29/30 (96.7%). The role
      of surgery, radiotherapy, chemotherapy, hormone therapy, and other treatments for
      extra-abdominal desmoid tumors is not well defined. When wide-margin resection
      and radiotherapy can be performed with limb preservation surgery, local control
      and complication rates compare favorably with those of other reported methods of
      treatment. Given the results and limitations of our study, we cannot make a
      definitive recommendation as to which modality--brachytherapy or EBRT--should be
      used in the treatment of extra-abdominal desmoid tumors.

PMID- 21734938
TI  - Literature recommended as study aids for the hip reconstruction section of the
      orthopaedic in-training examination.
AB  - One section of the Orthopaedic In-Training Examination (OITE) assesses knowledge
      about hip reconstruction. In the investigation reported here, we examined OITE
      hip reconstruction questions and sought to identify which literature can be
      recommended as study aids for this section of the test. All hip reconstruction
      questions on the OITE from 2002 to 2006 were characterized according to diagnosis
      and treatment. Journals cited most often in this section were identified from the
      OITE key. This content domain was compared with the literature in terms of
      overall proportion of questions/articles related to hip reconstruction and in
      terms of diagnoses and treatments. Of the 1375 OITE questions asked over the 5
      years, 79 were related to hip reconstruction. More than half of these hip
      reconstruction questions were related to primary total hip arthroplasty, with
      complications being the diagnosis tested most often. The results of this study
      suggest that residents may benefit from using general orthopedic journals when
      preparing for the OITE hip reconstruction section. When preparing an educational
      program, however, one should be aware that clinical journals may not reflect the
      OITE in terms of proportion of basic science and biomechanics articles.

PMID- 21734939
TI  - Underreporting of complementary and alternative medicine use among arthritis
      patients in an orthopedic clinic.
AB  - Underreporting of complementary and alternative medicine (CAM) use can negatively
      affect patient care. The degree of such underreporting in a clinical orthopedic
      setting was assessed in a cross-sectional study of 50 patients with
      osteoarthritis by administering a standard medical history and then a specific
      CAM-use questionnaire. Of these patients, 70% were using CAM, and 64%
      underreported CAM use on the standard medical history. The difference in CAM-use
      reporting between the 2 surveys was significant (P = .027). Mean individual CAM
      use was 1.53 times higher on the specific questionnaire than on the standard
      medical history. Study results demonstrate the prevalence of CAM use among
      orthopedic patients and significant increases in CAM reporting on the specific
      questionnaire.

PMID- 21734940
TI  - Primary synovial osteochondromatosis in the ankle: a case report.
AB  - Primary synovial osteochondromatosis results from the metaplasia of synovial
      tissue into cartilaginous tissue. This cartilaginous tissue then undergoes
      calcification and ossification, producing multiple osteochondral nodules. The
      cause of the metaplasia is unknown. Primary synovial osteochondromatosis is
      relatively rare and less common than secondary synovial osteochondromatosis. The
      primary form of the disease arises from the articular or tendon sheath synovium,
      whereas the secondary form is fragmented articular cartilage within the joint
      space. Primary synovial osteochondromatosis most commonly occurs in people aged
      30 to 40 years and is more prevalent in men. Symptoms include pain, swelling, and
      decreased range of motion. Because of their abundance of synovial tissue, larger
      joints are more likely to be affected than smaller joints. Knees are the most
      commonly affected joints, followed by, in no specific order, shoulders, hips, and
      elbows. The ankle and the joints of the hand are seldomly involved. In the early
      stage of the disease, only active synovitis is present, and radiographs are
      negative. In the late stage, loose bodies can be detected on radiographs.
      Grossly, these bodies are consistent with ossified nodules. Microscopically, the
      nodules are composed of cartilaginous material lined by synovial tissue with a
      central area of calcification.

PMID- 21734941
TI  - Gene transfer-mediated functional restoration for irradiated salivary glands.
AB  - Radiation therapy for malignant tumours in the head and neck region are
      inevitably associated with significant long-term injury to the salivary glands,
      often resulting in salivary gland hypofunction. The subsequent lack of saliva
      production leads to many functional and quality-of-life problems for affected
      patients and there is no effective method to eliminating this problem caused by
      radiation treatments. Although many studies have been done in animal models, the
      mechanism of this injury in humans is still unclear. In this review, an animal
      model (miniature pigs) used in irradiated research is mainly discussed. This
      review also presents the progress made to date on the gene transfer-mediated
      functional restoration of irradiated salivary glands and the possibilities
      provided by future interventions to prevent radiation damage to salivary glands.

PMID- 21734942
TI  - Fracture toughness, compressive strength and load-bearing capacity of short glass
      fibre-reinforced composite resin.
AB  - OBJECTIVE: To investigate the reinforcing effect of short E-glass fibre fillers
      on fracture related mechanical properties of dental composite resin with a semi
      interpenetrating polymer network (IPN) polymer matrix. METHODS: Experimental
      short fibre composite (FC) resin was prepared by mixing 22.5 wt% of short E-glass
      fibres, 22.5 wt% of IPN-resin and 55 wt% of silane treated silica fillers using a
      high speed mixing machine. Test specimens were made bar shaped (3 * 6 * 25 mm3),
      cylindrical (6 mm length * 3 mm diameter) and cubic (9.5 * 5.5 * 3 mm3) from the
      experimental FC resin and conventional particulate composite resin (Grandio) as
      control. The test specimens (n = 8) were either dry stored or water stored (37
      degrees C for 30 days) before the mechanical tests. A three-point loading test
      and compression test were carried out according to ISO 10477 and a static loading
      test was carried out using a steel ball (O 3.0 mm) with a speed of 1.0 mm/min
      until fracture. RESULTS: Experimental fibre composite had a significantly higher
      mechanical performance for fracture toughness (14 MNm-1.5), compression strength
      (129 MPa) and static load-bearing capacity (1584 N) than the control composite (2
      MNm-1.5, 112 MPa and 1031 N). CONCLUSION: The resin with short E-glass fibre
      fillers and IPN-polymer matrix yielded improved mechanical performance compared
      to the conventional particulate composite resin.

PMID- 21734943
TI  - Craniofacial morphology of Chinese patients with bilateral temporomandibular
      joint osteoarthrosis.
AB  - OBJECTIVE: To evaluate the morphological features of craniofacial structures in
      young patients affected by bilateral temporomandibular joint osteoarthrosis
      (TMJOA). METHODS: Forty-three males and 189 females aged 15 to 25 years who had
      lateral cephalograms and temporomandibular joint (TMJ) radiological examinations
      were included. They were classified into a TMJOA group and a control group,
      according to TMJ bony status. Thirty-two variables from lateral cephalogram were
      analysed by t test to evaluate the cranial and dentofacial differences between
      the two groups. RESULTS: TMJOA group showed a shorter posterior ramus height and
      shorter condyles, smaller SNB angle and larger ANB angle, smaller facial plane
      angle and larger angle of convexity, steeper mandibular plane angle and more
      vertical y-axis. CONCLUSION: Bilateral TMJOA is associated with dentofacial
      alterations characterised by a tendency toward retrognathism and shorter
      mandibles. However, the cause-and-effect relationship is yet to be clarified.

PMID- 21734944
TI  - Multidisciplinary management of congenitally missing teeth with osseointegrated
      dental implants: a long-term report.
AB  - OBJECTIVE: To describe a multidisciplinary approach to ensure optimal treatment
      and timing of treatment for these patients. METHODS: Ten patients with congenital
      missing teeth were treated with dental implants with a multidisciplinary
      approach, including orthodontics, prosthodontics, and/or orthognathic surgery,
      from 1997 to 2006 in the Department of Implant Dentistry, Peking University,
      Hospital of Stomatology. All patients were followed up over five years. Clinical
      and radiographic examinations were conducted for all the patients. A thorough
      diagnostic workup was used and the outline of the treatment planning was given
      from the prosthodontic point of view. RESULTS: A total of 31 implants were placed
      and restored for the 10 patients involved. Followup averaged 108.4 months (61-155
      months) after implant prosthetic functioning. With the multidisciplinary
      approach, a satisfactory treatment for these patients was acquired, with follow
      up for more than 5 years. The peri-implant marginal bone level was stable with
      bone resorption averaged 1.97 mm. Peri-implantitis was found in one patient with
      two implants and effectively treated with local anti-infection. Ceramic chips
      were observed in two cases and the crowns were re-fabricated. CONCLUSION: Implant
      restoration with an interdisciplinary approach provides an alternative way with
      predictable clinical results for patients with congenitally missing teeth.

PMID- 21734945
TI  - Eagle's syndrome treated with dissection of the styloid process via an extraoral
      approach combined with antidepressants.
AB  - OBJECTIVE: To evaluate the outcome of dissecting the styloid process via an
      extraoral approach combined with antidepressants for treating Eagle's syndrome.
      METHODS: Twenty-two patients with Eagle's syndrome underwent resection of the
      elongated styloid processes under general anaesthesia via an extraoral approach.
      All patients completed a self-rating depression scale preoperatively, and a score
      over 49 was defined as depression. The patients with depression were treated with
      fluoxetine 20 mg/day for 3 weeks postoperatively. In all patients, the abnormal
      length of the styloid process was resected. RESULTS: No surgical complications
      were observed. Eighteen (81.8%) patients had depression, and all 22 patients were
      followed for 7 to 26 months: 19 were symptom-free (86.4%), two patients with mild
      or moderate depression obtained almost complete remission of their symptoms, and
      one patient with severe depression obtained partial remission. No complications
      of medication occurred in any patient with depression, and all patients had a
      satisfactory cosmetic result and no paraesthesia. CONCLUSION: Dissection of the
      styloid process via an extraoral approach is simple and reliable; dissection of
      the styloid process combined with antidepressants (fluoxetine) is preferred for
      treating Eagle's syndrome.

PMID- 21734946
TI  - Effects of low-intensity swimming on radiation-induced leg contracture in mice.
AB  - OBJECTIVE: To evaluate the effects of low-intensity swimming on radiation-induced
      leg contracture. METHODS: Forty mice were randomly and equally divided into four
      groups: 1) irradiation; 2) swimming before irradiation; 3) swimming after
      irradiation; 4) swimming after contracture, and their left hind legs were exposed
      to gamma irradiation of 60 Gy. The mice were allowed to swim freely for 10
      minutes, three times per day. For group 2, the mice were allowed to swim for only
      1 week before irradiation. For group 3, the mice were allowed to swim immediately
      after irradiation until day 130, post-irradiation. For group 4, the mice were
      allowed to swim after leg contracture happened (on day 30 post-irradiation) until
      day 130, post-irradiation. The leg lengths and knee joint angles were measured.
      Leg contracture was defined as the decrease in the hind leg lengths and the knee
      joint angles of each animal. The ultrastructural changes of gastrocnemius muscles
      were observed using transmission electron microscopy. RESULTS: The radiation
      could result in leg contracture and mitochondrial injury of the muscles. However,
      the group of swimming immediately after irradiation had less leg contracture and
      no vacuolar degeneration in the mitochondria, compared with the other groups.
      CONCLUSION: Low-intensity swimming that began immediately after the mice were
      irradiated could effectively prevent the irradiated legs from contracture.
      Patients with irradiated mastication muscles were recommended to begin mouth
      opening exercises immediately after radiotherapy.

PMID- 21734947
TI  - Effects of hydrogen peroxide-containing bleaching on cariogenic bacteria and
      plaque accumulation.
AB  - OBJECTIVE: To evaluate the effects of a commercial bleaching agent containing 36%
      hydrogen peroxide on the clinical plaque index and Streptococcus mutans and
      Lactobacilli counts in dental plaque and saliva in vivo. METHODS: Twenty
      volunteers were recruited in the present study. Evaluation of plaque index and
      bacteria counts in plaque and saliva was performed before bleaching the teeth,
      and 3 days, 2 weeks and 4 weeks post-treatment. RESULTS: Quigley-Hein Plaque
      Index and Modified Navy Plaque Index were significantly lower on day three after
      bleaching compared to that before bleaching and the other time points after
      bleaching. The total number of bacteria in the plaque on day three after
      bleaching was also less than that before bleaching and the other time points
      after bleaching. The Streptococcus mutans counts in the plaque and saliva four
      weeks after bleaching were decreased significantly compared to that before
      bleaching. CONCLUSION: Hydrogen peroxide bleaching can decrease plaque
      accumulation and cariogenic bacteria for a short period of time.

PMID- 21734948
TI  - Investigation of the psychological status of 162 female TMD patients with
      different chronic pain severity.
AB  - OBJECTIVE: To evaluate the level of psychosocial difficulties in patients with
      temporomandibular disorders (TMD) by using the Symptom Checklist 90 revised (SCL
      90-R), and determine whether there is an association between psychosocial status
      and chronic pain severity. METHODS: One hundred and sixty-two female patients who
      came to the Center for TMD and Orofacial Pain of Peking University Hospital of
      Stomatology were randomly included in this study. SCL-90-R was used to assess the
      psychological status of the TMD patients. This instrument was also used to assess
      psychological status and pain-related disability in chronic pain patients and a
      seven-item questionnaire was used to grade chronic pain severity (GCP).
      Univariate analysis of variance and correlation analysis were performed to
      determine the association between psychological status and chronic pain severity.
      RESULTS: A total of 126 female TMD patients complained of pain in the
      temporomandibular joint. One hundred and sixteen patients had low disability,
      with 83 (51.3%) having low intensity pain (Grade I), 30 (18.5%) having high
      intensity pain (Grade II) and only 13 (8%) with high disability (Grade III pain).
      The patients were divided into four groups according to their GCP scores. The
      scores of all the factors of SCL-90-R were significantly different among the
      groups. The incidence of psychosocial symptoms was also significantly different
      among the groups. The psychosocial status of patients with high disability was
      the worst among the four groups. CONCLUSION: The GCP severity is a suitable tool
      to assess the psychosocial and physical status of TMD chronic pain. Some TMD
      patients have psychological problems and symptoms of psychopathology, especially
      those with high disability. Physicians should keep this possibility in mind when
      treating patients with TMD chronic pain.

PMID- 21734949
TI  - Clinical evaluation of a gingiva-coloured material, Comp Natur: a 3-year
      longitudinal study.
AB  - OBJECTIVE: To report on a three-year clinical evaluation of the gingiva-coloured
      compomer (Comp Natur, Voco, Germany). METHODS: Twelve patients with cervical
      lesions as a result of either gingival recession or worn root dentine were
      included in this study. In total, 106 restorations were evaluated by two
      examiners at baseline, 6-month and 3-year recalls. RESULTS: Ninety-nine
      restorations (99/106, 93.4%) were reported with having a good retention in the
      oral cavity at the 3-year recall. Ninety-two of the 99 restorations were
      evaluated as excellent for colour match. Marginal discoloration was slightly
      higher at the 3-year recall, while surface texture and anatomic form were
      significant. Marginal adaptation was not statistically important at the 3-year
      recall. There was no problem related to caries and postoperative sensitivity.
      CONCLUSION: Comp Natur is an acceptable treatment choice for cervical defects
      with recessed gingiva.

PMID- 21734950
TI  - Diverse growth patterns in an intraosseous ameloblastoma: a case report.
AB  - Desmoplastic ameloblastoma (DA) is a benign but locally invasive variant of the
      solid/multicystic ameloblastoma (SMA). In the recent World Health Organization
      classification of odontogenic tumours, DA has been characterised as a variant,
      with specific clinical, radiographic and histopathological features. A possible
      'transitional' form of DA, showing microscopic features of the desmoplastic
      variant together with areas typical of classic follicular or plexiform
      ameloblastoma, has been described as a 'hybrid' lesion of ameloblastoma (HLA). A
      unique case with synchronous emergence of desmoplastic and unicystic
      ameloblastoma (different growth patterns) in the mandible of a 50-year-old male
      is reported.

PMID- 21734952
TI  - pH changes upon mixing of single-step self-etching adhesives with powdered
      dentin.
AB  - PURPOSE: Single-step self-etching adhesives have been developed as a bonding
      material that adheres to the tooth surface. The adhesives contain acidic resin
      monomers that penetrate the dentin but can be neutralized to stop the reaction.
      This study aimed to improve understanding of the pH changes that occur when self
      etching adhesives are mixed with dentin powder. MATERIALS AND METHODS: Dentin
      disks obtained from extracted bovine incisors were milled and pulverized into a
      fine powder. The powder was mixed with diluted self-etching adhesives, and pH
      changes were measured by a solid-state pH sensor connected to a pH meter at
      various time points after the start of mixing. Data were analyzed by Tukey's
      Honestly Significant Difference (HSD) test and Dunnett's test at a significance
      level of 0.05. Precipitates from the adhesive/ dentin powder mixture were
      observed by scanning electron microscopy (SEM). RESULTS: The baseline pH values
      of the self-etching adhesives ranged from 0.97 to 2.83. After mixing with the
      dentin powder, the pH values significantly increased, ranging from 6.30 to 7.11
      at 180 s after mixing. SEM observation revealed products of the reaction between
      dentin powder and self-etching adhesive which indicate a chemical reaction
      between the functional monomer and dentin. CONCLUSION: Dentin has a strong
      modulation effect against the acidity of self-etching adhesives.

PMID- 21734953
TI  - The influence of cutting speed and cutting initiation location in specimen
      preparation for the microtensile bond strength test.
AB  - PURPOSE: This study evaluated the effect of cutting initiation location and
      cutting speed on the bond strength between resin cement and feldspathic ceramic.
      MATERIALS AND METHODS: Thirty-six blocks (6.4 x 6.4 x 4.8 mm) of ceramic (Vita
      VM7) were produced. The ceramic surfaces were etched with 10% hydrofluoric acid
      gel for 60 s and then silanized. Each ceramic block was placed in a silicon mold
      with the treated surface exposed. A resin cement (Variolink II) was injected into
      the mold over the treated surface and polymerized. The resin cement-ceramic
      blocks were divided into two groups according to experimental conditions: a)
      cutting initiation location - resin cement, ceramic and interface; and b) cutting
      speed - 10,000, 15,000, and 20,000 rpm. The specimens were sectioned to achieve
      non-trimmed bar specimens. The microtensile test was performed in a universal
      testing machine (1 mm/min). The failure modes were examined using an optical
      light microscope and SEM. Bond strength results were analyzed using one-way ANOVA
      and Tukey's test (alpha = 0.05). RESULTS: Significant influences of cutting speed
      and initiation location on bond strength (p < 0.05) were observed. The highest
      mean was achieved for specimens cut at 15,000 rpm at the interface (15.12 +/-
      5.36 MPa). The lowest means were obtained for specimens cut at the highest
      cutting speed in resin cement (8.50 +/- 3.27 MPa), and cut at the lowest cutting
      speed in ceramic (8.60 +/- 2.65 MPa). All groups showed mainly mixed failure (75%
      to 100%). CONCLUSION: The cutting speed and initiation location are important
      factors that should be considered during specimen preparation for microtensile
      bond strength testing, as both may influence the bond strength results.

PMID- 21734954
TI  - Shear bond strength of deciduous and permanent bovine enamel.
AB  - PURPOSE: The use of bovine teeth as a substitute for human enamel has been
      proposed for dental studies. The aim of this study was to determine the shear
      bond strength and Adhesive Remnant Index (ARI) of deciduous and permanent bovine
      teeth. MATERIALS AND METHODS: Twenty deciduous and 20 permanent extracted bovine
      teeth were embedded in resin blocks. Stainless steel conventional orthodontic
      brackets were bonded to the teeth using an orthodontic adhesive. All samples were
      tested in shear mode on a testing machine. ARI scores were then recorded.
      Statistical analysis was performed to determine significant differences in bond
      strength and ARI scores. RESULTS: The bond strength of permanent bovine teeth was
      significantly higher (p = 0.0010) than that of the deciduous teeth. ARI scores
      showed no significant differences (p = 0.74). CONCLUSION: Deciduous teeth show
      lower shear bond strength than permanent teeth.

PMID- 21734955
TI  - Bonding efficacy of new self-etching, self-adhesive dual-curing resin cements to
      dental enamel.
AB  - PURPOSE: This study evaluated the efficacy of the union between two new self
      etching self-adhesive resin cements and enamel using the microtensile bond
      strength test. MATERIALS AND METHODS: Buccal enamel of 80 bovine teeth was
      submitted to finishing and polishing with metallographic paper to a refinement of
      #600, in order to obtain a 5-mm2 flat area. Blocks (2 x 4 x 4 mm) of laboratory
      composite resin were cemented to enamel according to different protocols: (1)
      untreated enamel + RelyX Unicem cement (RX group); (2) untreated enamel + Bifix
      SE cement (BF group); (3) enamel acid etching and application of resin adhesive
      Single Bond + RelyX Unicem (RXA group); (4) enamel acid etching and application
      of resin adhesive Solobond M + Bifix SE (BFA group). After 7 days of storage in
      distillated water at 37 degrees C, the blocks were sectioned for obtaining
      microbar specimens with an adhesive area of 1 mm2 (n = 120). Specimens were
      submitted to the microtensile bond strength test at a crosshead speed of 0.5
      mm/min. The results (in MPa) were analyzed statistically by ANOVA and Tukey's
      test. RESULTS: Enamel pre-treatment with phosphoric acid and resin adhesive (27.9
      and 30.3 for RXA and BFA groups) significantly improved (p <= 0.05) the adhesion
      of both cements to enamel compared to the union achieved with as-polished enamel
      (9.9 and 6.0 for RX and BF). CONCLUSION: Enamel pre-treatment with acid etching
      and the application of resin adhesive significantly improved the bond efficacy of
      both luting agents compared to the union achieved with as-polished enamel.

PMID- 21734956
TI  - Improvement of exposure times: effects on adhesive properties and resin-dentin
      bond strengths of etch-and-rinse adhesives.
AB  - PURPOSE: This study evaluated the effect of prolonged polymerization times on the
      microtensile resin-dentin bond strength (MUTBS), degree of conversion of adhesive
      films (DC) and silver nitrate uptake (SNU) for an ethanol/water- (Adper Single
      Bond 2, [SB]) and an acetone-based (One Step Plus, [OS]) etch-and-rinse adhesive.
      MATERIALS AND METHODS: Thirty caries-free extracted molars were included in this
      study. The occlusal enamel of all teeth was removed by wet grinding the occlusal
      enamel on 180-grit SiC paper. Adhesives were applied according to the
      manufacturer's instructions, but they were light cured for 10, 20 and 40 s at 600
      mW/cm2. Bonded sticks (0.6 mm2) were tested in tension (0.5 mm/min). Two bonded
      sticks from each tooth were immersed in an ammoniacal solution of silver nitrate
      (24 h), photodeveloped (8 h), and analyzed by SEM. The DC of the adhesives was
      evaluated under Fourier Transformed Infra-Red spectroscopy (FTIR). Data for each
      property were analyzed by two-way ANOVA and Tukey's test (alpha = 0.05). RESULTS:
      Statistically higher MUTBS and DC were observed for SB and OS when both adhesives
      were light cured for 40 s in comparison with 10 s. For OS, the MUTBS in the 20-
      and 40-s groups did not differ statistically, while for SB it did. Higher
      prolonged exposure times did not prevent nanoleakage within the hybrid layer for
      all groups regardless of the adhesive. CONCLUSION: This study supports the
      hypothesis that exposure times longer than those recommended can improve the
      degree of conversion of adhesive films and the immediate resin-dentin bonds. The
      prolonged curing times (20 and 40 s) for polymerization of simplified adhesives
      resulted in an increase in the degree of conversion of the adhesive films and
      resin-dentin bond strengths but did not reduce the nanoleakage within the hybrid
      layer.

PMID- 21734957
TI  - Hydrolytic stability of one-step self-etching adhesives bonded to dentin.
AB  - PURPOSE: To evaluate the hydrolytic stability of three one-step self-etching
      adhesives (1-SEAs) bonded to dentin through bond strength testing and ultra
      morphological interfacial analysis before and after long-term thermocycling.
      MATERIALS AND METHODS: Eighteen flattened mid-coronal dentin surfaces of
      extracted human molars were subjected to bonding treatment using three 1-SEAs
      (Clearfil S3 Bond, Kuraray (S3), G-Bond, GC (GB), Absolute, Dentsply-Sankin
      (AB)), after which the bonded surfaces were built up with composite. After
      storage overnight at 37 degrees C, the specimens were sectioned into slabs and
      further trimmed into an hourglass shape with an interface area of approximately 1
      mm2. The specimens were left untouched (control) or were thermocycled for 100,000
      cycles. The microtensile bond strength (MUTBS) was measured and the
      ultrastructure of the adhesive/dentin interface characterized using transmission
      electron microscopy (TEM). RESULTS: Long-term thermocycling significantly
      decreased the MUTBS of all one-step adhesives tested (p < 0.05, one way ANOVA and
      Games-Howell test). TEM revealed a similar interfacial ultrastructure before and
      after thermocycling for S3. For GB, many voids were observed at the interface
      after 100,000 thermocycles. Regarding AB, collagen fibrils could no longer be
      clearly observed upon staining, while the adjacent unaffected dentin was rich in
      voids. CONCLUSION: The bond strength and ultramorphological data demonstrated
      that the bond of 1-SEAs to dentin degrades with time, although the degree of
      degradation is obviously material dependent.

PMID- 21734958
TI  - Effect of surface sealants on microleakage of Class II restorations after
      thermocycling and long-term water storage.
AB  - PURPOSE: To evaluate interface degradation leading to marginal microleakeage in
      Class II restorations that had received an application of surface sealant at the
      tooth/restoration interface or not. MATERIALS AND METHODS: Eighty bovine incisors
      were used, and the teeth were split obliquely, 10 mm from the amelodentinal
      proximal junction, and finished with water abrasive papers to obtain a smooth,
      flat incisal surface. Cavities were made to simulate Class II preparations (8 mm
      high, 4 mm wide and 1.5 mm deep), and the restorations were performed with a
      composite resin. Teeth were then randomly allocated into 8 groups according to
      the surface sealant (none, Fortify, Single Bond 2, or Scothbond MP Plus) and
      aging process (none or thermocycling and storage for 6 months). Microleakage was
      then evaluated using a dye penetration method immediately after the restoration
      or after aging. The samples were triturated and assessed by spectrophotometer.
      RESULTS: Microleakage was statistically similar in all groups when assessed
      immediately after the restorative procedure. After aging, teeth sealed with
      Fortify presented better results than the other groups. CONCLUSION: Aging causes
      interface degradation and increased microleakage. Surface sealant can reduce
      these effects and decrease microleakage in Class II restorations.

PMID- 21734959
TI  - Evaluation of zirconia/resin bond strength and interface quality using a new
      technique.
AB  - PURPOSE: Selective infiltration etching is a newly developed surface treatment
      used to modify the surface of zirconiabased materials, rendering it ready for
      bonding with resin cements. The aim of this study was to evaluate zirconia/resin
      bond strength and durability using the new technique. MATERIALS AND METHODS:
      Zirconia disks received one of the following surface treatments: selective
      infiltration etching or airborne-particle abrasion with 50-MUm aluminum oxide
      particles, while as-sintered surfaces served as control. The zirconia disks were
      bonded to pre-aged composite resin disks using a light-polymerized adhesive resin
      (Panavia F 2.0). Zirconia resin bond strength was evaluated using the
      microtensile bond strength test (MTBS) and the test was repeated after each of
      the following intervals of accelerated artificial aging: thermocycling (10,000
      cycles between 5 degrees C and 55 degrees C), 4 weeks, 26 weeks, 52 weeks, and
      104 weeks of water storage (37 degrees C ). A repeated measures ANOVA and
      Bonferroni post-hoc tests were used to analyze the data (n = 18, alpha = 0.05).
      RESULTS: There were significant differences in the MTBS values between the three
      test groups at each of the test intervals (p < 0.001). After 2 years of
      artificial aging, all specimens of the control group demonstrated spontaneous
      failure, while significant reduction in the bond strength of the particle-abraded
      groups was observed (21.3 MPa). The bond strength of the selective infiltration
      etched group was relatively stable (44.1 MPa) after completion of artificial
      aging. CONCLUSION: Within the limitations of this study, micromechanical
      retention and adhesion promoters are prerequisites for establishing a strong and
      durable bond to zirconia-based materials.

PMID- 21734960
TI  - Evaluation of bond strength of self-adhesive cements to dentin with or without
      application of adhesive systems.
AB  - PURPOSE: To evaluate the bond strength of indirect restorations to dentin using
      self-adhesive cements with and without the application of adhesive systems.
      MATERIAL AND METHODS: Seventy-two bovine incisors were used, in which the buccal
      surfaces were ground down to expose an area of dentin measuring a minimum of 4 x
      4 mm. The indirect resin composite Resilab was used to make 72 blocks, which were
      cemented onto the dentin surface of the teeth and divided into 4 groups (n = 18):
      group 1: self-adhesive resin cement BiFix SE, applied according to manufacturer's
      recommendations; group 2: self-adhesive resin cement RelyX Unicem, used according
      to manufacturer's recommendations; group 3: etch-and-rinse Solobond M adhesive
      system + BiFix SE; group 4: etch-and-rinse Single Bond 2 adhesive system + RelyX
      Unicem. The specimens were sectioned into sticks and subjected to microtensile
      testing in a universal testing machine (EMIC DL- 200 MF). Data were subjected to
      one-way ANOVA and Tukey's test (alpha = 5%). RESULTS: The mean values (+/-
      standard deviation) obtained for the groups were: group 1: 15.28 (+/- 8.17)a,
      group 2: 14.60 (+/- 5.21)a, group 3: 39.20 (+/- 9.98)c, group 4: 27.59 (+/-
      6.57)b. Different letters indicate significant differences (ANOVA; p = 0.0000).
      CONCLUSION: The application of adhesive systems before self-adhesive cements
      significantly increased the bond strength to dentin. In group 2, RelyX Unicem
      associated with the adhesive system Single Bond 2 showed significantly lower mean
      tensile bond strengths than group 3 (BiFix SE associated with the etch-and-rinse
      Solobond M adhesive system).

PMID- 21734961
TI  - Effect of ridge-lap surface treatments on the bond of resin teeth to denture
      base.
AB  - PURPOSE: To test in vitro the shear bond strength of resin teeth to an acrylic
      resin denture base given different ridgelap surface treatments. MATERIALS AND
      METHODS: Ninety rectangular dies were made with wax and traditionally invested in
      metallic or plastic flasks. The stone molds were covered with silicone, in which
      were included an acrylic molar with a wax stick fixed on the ridge lap surface.
      After deflasking, the wax sticks were removed, the teeth were cleaned with
      detergent, the ridge lap surface was submitted to different treatments
      (unmodified, bur-cut grooves, aluminum oxide particle sandblasting, monomer
      swelling, and primer swelling), and the teeth were replaced in the silicone
      molds. Metallic flasks were placed in a thermopolymerizing unit to polymerize
      heat-curing denture-base polymer, and plastic flasks were placed in a domestic
      microwave oven at 900 W to polymerize microwaveable denture base polymer. After
      deflasking, the specimens were submitted to the shear bond test in an Instron
      machine at a cross-speed of 1 mm/min. Results were submitted to ANOVA and Tukey's
      test (5%). RESULTS: Shear bond strength values were influenced by the ridge-lap
      surface treatments only in the microwaved polymer. Sandblasting + monomer
      swelling and sandblasting + primer swelling interactions yielded lower strengths
      for microwaved polymer. Only the unmodified surfaces presented a significant
      difference when the resins were compared, where the microwaved polymer showed a
      higher value. CONCLUSION: Different tooth ridge-lap surface treatments promoted
      different strengths of the tooth/resin bond.

PMID- 21734962
TI  - Minimally invasive dentistry.

PMID- 21734963
TI  - Current aspects of restoring traumatically fractured teeth.
AB  - Endodontic and restorative considerations are of primary significance in the
      treatment of tooth fractures. Since exposed dentinal tubules permit invasion of
      bacteria into the endodontic system, a protective dressing must be applied as
      part of the emergency treatment. Provided the dentin wound has been sealed,
      restorative treatment can also be carried out at a later stage. The fractured
      tooth fragment can be reattached using adhesive protocols in order to restore
      function and esthetic appearance. If reattachment is difficult or impossible, eg,
      in cases of multiple or missing fragments, current composite materials enable
      excellent esthetic results. Minimally-invasive direct composite restorations are
      preferred over the more invasive indirect restorations, at least in immature
      teeth with an extensive coronal pulp dimension. Restorative treatment of crown
      root fractures is frequently demanding due to inaccessible subgingival fracture
      margins. Extrusion of the remaining root is an alternative method to surgical
      crown lengthening for re-establishing the biological width. This can be carried
      out either orthodontically (forced eruption), or surgically (intra-alveolar
      transplantation). Although the treatment of crown-root fractures is one of the
      most technically sensitive procedures in dental traumatology and is frequently
      considered as a long-term temporary restoration, tooth conservation up to the age
      at which implants can be placed may be regarded as a success.

PMID- 21734964
TI  - A comprehensive and conservative approach for the restoration of abrasion and
      erosion. part II: clinical procedures and case report.
AB  - This article proposes a comprehensive and conservative approach to the treatment
      of tooth wear, based on the application of minimally invasive composite
      restorations to treat both anterior and posterior decay. Three treatment options
      were considered, in relation to the severity of tissue loss and size of existing
      posterior restorations. Posterior tooth status actually will guide the clinician
      toward the most appropriate restorative option. In the presence of limited tissue
      loss and small fillings, only direct restorations are considered. With moderate
      tissue loss and medium size existing restorations, a mix of direct and indirect
      composite restorations is preferred, and with extensive tissue loss and large
      restorations, mainly indirect restorations will be chosen. The restoration of
      anterior guidance and a proper smile line are reestablished using adhesive
      restorations, including primarily direct composite buildups; in the presence of
      more severe tissue destruction, loss of facial morphology or discoloration,
      veneers and possibly crowns can be considered. The driving force behind the
      concept presented in this article is to intercept tissue destruction and restore
      proper tooth biomechanics, function, and esthetics using adhesive restorations
      which do not further invade hard tissues.

PMID- 21734965
TI  - SAEF - Smile's Aesthetic Evaluation form: a useful tool to improve communications
      between clinicians and patients during multidisciplinary treatment.
AB  - Today, physical appearance plays a major role in self-esteem and, as a result,
      also in the overall satisfaction of the person. Facial esthetics plays a crucial
      role, with the smile being the protagonist. A multidisciplinary approach,
      including several specialties of dentistry, is usually needed in order to create
      a pleasing end result. With the Smile's Aesthetic Evaluation Form (SAEF), the
      authors propose a new evaluation of the esthetics of the smile. It uses both
      static (photographs) and dynamic (videos) analysis, followed by several objective
      and subjective items, thus improving the communication between the different
      dental specialists and laboratory technicians. The SAEF also provides the patient
      knowledge of the disharmonies of the smile and increases the patient's
      comprehension and acceptance of treatment. It is organized in such a way as to
      provide an understanding of the esthetic parameters of the smile individually,
      and, simultaneously, evaluate the quality of the smile for the specific case.
      This form is designed to detect small dental anomalies when the patient is not
      content with his/her smile, but is unable to pinpoint the parameters that cause
      this dissatisfaction. This esthetic evaluation form can be a useful additional
      tool to the clinical diagnostic procedure. In order for the analysis to be fully
      understood, an example of its use will be presented in a clinical case. CASE
      REPORT: A 28-year-old female patient, dissatisfied with her smile, presented to
      the Orthodontic Department of Tel Aviv University. She had undergone orthodontic
      treatment in the past. She presented a relapse in the mandible. The relapse in
      the mandibular arch was to be corrected with Invisalign. For the maxillary arch,
      the SAEF was completed in order to improve the communication between the
      orthodontist, patient, and cosmetic dentist to correct the incorrect parameters
      highlighted in the analysis.

PMID- 21734966
TI  - Prefabricated composite veneers: historical perspectives, indications and
      clinical application.
AB  - Veneering anterior teeth is a well-established technique, which was brought to
      Dentistry by Dr Pincus as early as 1937. From the mid-1970s, boosted by the
      development of composites and adhesive techniques, various concepts emerged
      including direct composite restorations, prefabricated composite veneers and of
      course, individualized porcelain indirect veneers. The prefabricated composite
      veneer option was however soon abandoned due to former technological limitations.
      Recently, the creation of a new shade guide comprising enamel shells revitalized
      this "old idea," and in combination with a high pressure and temperature molding
      process followed by a laser surface vitrification, a novel, improved composite
      prefabricated system (Venear, Edelweiss Dentistry) was born. This paper provides
      an overview of the potential indications and clinical protocol of this original
      veneering technique.

PMID- 21734967
TI  - Use of the ditramax system to communicate esthetic specifications to the
      laboratory.
AB  - Prosthetic restoration of the anterior teeth is a major esthetic challenge.
      Esthetic treatment consists of creating pleasantly proportioned teeth and
      integrating them harmoniously into the patient's gingiva, lips, and face. The
      communication of clinical data to the laboratory is critical to the success of
      any esthetic treatment. The purpose here is to present a straightforward,
      efficient, and reproducible means of communicating esthetic specifications to
      ceramists, allowing them to work as though the patient was actually in front of
      them, with access to all of the major facial esthetic criteria.

PMID- 21734968
TI  - A survey on variability in shade selection by practicing dentists.
AB  - PURPOSE: To evaluate the variability in shade selection for general practitioners
      (GPs) and postgraduate (MDS) practitioners and to assess if a shade selection
      bias exists. MATERIALS AND METHODS: 2070 samples of the chosen shade(s) by 31 GPs
      and 18 MDS practitioners in the form of work authorization forms and slips were
      collected from dental laboratories. The mouth was divided into four quadrants:
      maxillary anteriors and posteriors, and mandibular anteriors and posteriors. The
      data was grouped and analyzed. RESULTS: The same shade or combination was
      repeated by the GPs and the MDS practitioners 38% and 35% of the time,
      respectively. The GP group prescribed a single shade in 84% of cases and a
      combination of two shades per tooth in 14% of cases, in contrast to the MDS
      practitioners, who prescribed a single shade in 51% of cases and two shades in
      47% of cases. CONCLUSION: A shade selection bias exists among both general and
      MDS practitioners, as a particular shade or combination was repeated a
      significant number of times. However, MDS practitioners use a combination of two
      shades more frequently than general practitioners, who rely mostly on a single
      shade for a tooth.

PMID- 21734969
TI  - Biologic interfaces in esthetic dentistry. Part I: the perio/restorative
      interface.

PMID- 21734970
TI  - Biologic Interfaces in esthetic dentistry. Part II: the peri-implant/restorative
      interface.

PMID- 21734971
TI  - Nd:YAG laser irradiation of etched/unetched dentin through an uncured two-step
      etch-and-rinse adhesive and its effect on microtensile bond strength.
AB  - PURPOSE: To evaluate whether Nd:YAG laser irradiation of etched and unetched
      dentin through an uncured adhesive affected the microtensile bond strength
      (uTBS). MATERIALS AND METHODS: Flat dentin surfaces were created in 19 extracted
      human third molars. Adper Single Bond (SB) adhesive was applied over etched
      (groups 1 to 3) or unetched dentin (groups 4 to 6). The dentin was then
      irradiated with a Nd:YAG laser through the uncured adhesive, using 0.75 or 1 W
      power settings, except for the control groups (groups 1 and 4). The adhesive was
      light cured and composite crowns were built up. After 24 h, the teeth were
      sectioned into beams, with cross-sectional areas of 0.49 mm2, and were stressed
      under tension. Data were statistically analyzed using two-way ANOVA and Tukey's
      test (alpha = 5%). Dentin surfaces of fractured specimens and the interfaces of
      untested beams were observed under scanning electron microscopy (SEM). RESULTS:
      Acid etching, laser irradiation, and their interaction significantly affected
      bonding (p < 0.05). Laser irradiation did not improve bonding of etched dentin to
      resin (p > 0.05). However, higher uTBS means were found on unetched lased dentin
      (groups 5 and 6), but only in comparison to group 4, where neither lasing nor
      etching was performed. Groups 4 to 6 showed the lowest uTBS means among all
      groups tested (p < 0.05). Laser irradiation did not change the characteristics of
      the hybrid layers created, while solidification globules were observed on lased
      dentin surfaces under SEM. CONCLUSION: Laser irradiation of dentin through the
      uncured adhesive did not significantly improve the uTBS in comparison to the
      suggested manufacturer's technique.

PMID- 21734972
TI  - Ethanol-wet bonding technique may enhance the bonding performance of contemporary
      etch-and-rinse dental adhesives.
AB  - PURPOSE: To determine whether bonds of contemporary etch-and-rinse adhesives made
      with ethanol-wet bonding are stronger and more durable than those made with water
      wet bonding, and to explore the possible reasons for the bonding results.
      MATERIALS AND METHODS: Flat surfaces of midcoronal dentin were made in extracted
      human third molars. The dentin surfaces were randomized into 6 groups according
      to bonding techniques (water- vs ethanol-wet bonding) and dental adhesives
      [Single Bond 2 (SB), Prime Bond NT (PB), and Gluma Comfort Bond (GB)]. After
      etching and rinsing, dentin surfaces were either left water-moist or immersed in
      ethanol. Following adhesive application and composite buildups, the bonded teeth
      were sectioned into beams for microtensile bond strength evaluation with or
      without NaOCl challenge. The morphology of the hybrid layer was analyzed with
      SEM. The wettability of water- vs. ethanol-saturated dentin was evaluated. The
      concentrations of non-volatile ingredients in the adhesives were compared.
      RESULTS: Compared to water-wet bonding, ethanol-wet bonding yielded similar (p >
      0.05 for PB and GB) or higher (p < 0.05 for SB) 24-h bond strength, displayed
      significantly higher bond strength after chemical challenge (p < 0.05, for all
      three adhesives), and produced more even hybrid layers. Moreover, ethanol
      saturated dentin exhibited a lower contact angle than water-saturated specimens,
      and the concentrations of non-volatile ingredients of the adhesives decreased in
      the order of SB > GB > PB. CONCLUSION: Ethanol-wet bonding could improve the
      bonding efficacy of contemporary etch-and-rinse adhesives, probably due to the
      good wettability of ethanol-saturated dentin and the structure of the hybrid
      layer. Moreover, this positive effect of ethanol-wet bonding might be influenced
      by the composition of adhesives.

PMID- 21734973
TI  - Full-mouth minimally invasive adhesive rehabilitation to treat severe dental
      erosion: a case report.
AB  - Dental erosion is increasing, and only recently are clinicians starting to
      acknowledge the problem. A prospective clinical trial investigating which
      therapeutic approach must be undertaken to treat erosion and when is under way at
      the University of Geneva (Geneva Erosion Study). All patients affected by dental
      erosion who present with signs of dentin exposure are immediately treated using
      only adhesive techniques. In this article, the full-mouth adhesive rehabilitation
      of one of these patients affected by severe dental erosion (ACE class IV) is
      illustrated. By the end of the therapy, a very pleasing esthetic outcome had been
      achieved (esthetic success), all of the patient's teeth maintained their
      vitality, and the amount of tooth structure sacrificed to complete the adhesive
      full-mouth rehabilitation was negligible (biological success).

PMID- 21734974
TI  - Peel bond strength of two silicone soft liners to a heat-cured denture base
      resin.
AB  - PURPOSE: This study investigated the peel strength of two different soft liners
      to a polymethylmethacrylate (PMMA) denture base resin before and after
      thermocycling. MATERIALS AND METHODS: The silicone-based soft liner materials
      tested were Molloplast B and Permaflex; the denture base material was a heat
      cured acrylic resin, Meliodent. A total of 40 specimens was prepared using
      rectangular molds with dimensions of 100 x 10 x 2 mm for PMMA and 150 x 10 x 2 mm
      for soft liners, as described in ASTM-D903-93. For each of the liner materials,
      10 specimens were packed against a cured PMMA denture base surface as recommended
      by the manufacturers. The other 10 specimens were packed against PMMA denture
      base dough and processed together. In each group, 5 of the specimens were tested
      directly, while the other 5 were thermocycled in a water bath (5 degrees C to 55
      degrees C; 3000 cycles) before testing. Peel testing was performed using an
      Instron testing machine. RESULTS: The results revealed that peel strength values
      of the Permaflex specimens prepared according to the manufacturer's
      recommendations were significantly higher than those of Molloplast B (p < 0.05).
      However, when packing was done against uncured PMMA dough, the difference between
      the specimens of two liners was not significant. Thermocycling led to significant
      decreases in the peel strength of both Permaflex liner specimens packed against
      cured/uncured PMMA resin surfaces (p < 0.05), whereas this process did not affect
      the strength of Molloplast B specimens. CONCLUSION: Results indicated that the
      material Molloplast B was superior to the material Permaflex in terms of peel
      strength when the specimens were simultaneously polymerized with PMMA and
      thermocycled.

PMID- 21734975
TI  - Influence of fabrication techniques and artificial aging on the fracture
      resistance of different cantilever zirconia fixed dental prostheses.
AB  - PURPOSE: To evaluate the influence of dynamic fatigue on fracture load and
      failure mode of different types of adhesive zirconia restorations. MATERIALS AND
      METHODS: Eighty adhesive cantilever fixed dental prostheses (CFDP) were
      fabricated and assigned to four equal groups (n = 20) using the following
      materials and techniques. Group 1: machine copy-milling zirconia (Cercon), group
      2: manual copy-milling technique (ZirkonZahn), group 3: slip casting technique
      (Vita In-ceram Zirconia), group 4: metal-ceramic CFDP. Specimens in groups 1and 2
      received selective infiltration-etching surface treatment, specimens in group 3
      were acid etched with hydrofluoric acid and silanated, while those of group 4
      were airborne particle abraded. All specimens were bonded with resin cement
      (Panavia F2.0) and thermocycled (5000 cycles/ 5 to 55 degrees C). Then, half the
      number of the specimens of each group (n = 10) underwent dynamic loading (one
      million cycles at alternating loads between 10 and 40 N in a water bath at 37
      degrees C). All specimens were subjected to one-cycle loading to failure to
      evaluate fracture resistance. One-way and two-way ANOVA and Bonferroni post-hoc
      tests were used to analyze the data (alpha = 0.05). The intaglio surfaces of
      fractured specimens were examined using stereomicroscopy and scanning electron
      microscope (SEM). RESULTS: Statistical analysis revealed that the failure load of
      metal (413 +/- 26 N) and machine copy-milled zirconia (368 +/- 24 N) restorations
      was significantly higher (F = 129, p < 0.001) than manually copy-milled (316 +/-
      18) and In-ceram zirconia (210 +/- 17) restorations. Dynamic fatigue
      significantly (p < 0.03) reduced failure load of the manually copy-milled and In
      ceram zirconia restorations, while metal and machine copy-milling zirconia
      restorations were not influenced by fatigue. CONCLUSIONS: The fatigue strength of
      adhesive zirconia restorations is influenced by cyclic loading and the technique
      used to manufacture these restorations.

PMID- 21734976
TI  - Extent of cement polymerization along dowel space as a function of the
      interaction between adhesive and cement in fiber post cementation.
AB  - PURPOSE: To assess whether the polymerization extent of cement is influenced by
      curing mode of the adhesive and/or by photoactivation of the cement. MATERIALS
      AND METHODS: One hundred five root segments were prepared from endodontically
      treated teeth. After post space preparation, the root segments were randomly
      divided into 7 groups, based on the cementation procedure to lute RelyX Fiber
      Posts (3M ESPE): 1. Variolink II (V, Ivoclar Vivadent); 2. V light-cured (LC); 3.
      Excite LC (ELC, Ivoclar Vivadent)/V; 4. ELC/V LC; 5. ELC-V LC (One Shot); 6.
      Excite DSC (EDSC)/V; 7. EDSC-V LC (One Shot). Each root segment was submitted to
      the acetone shake test to remove the unpolymerized resin and then cut
      longitudinally. On each half, the extent of cure of the cement was measured with
      image analysis software. RESULTS: The deepest and basically complete
      polymerization was obtained with EDSC (groups 6 and 7), regardless of whether
      light curing was performed. The extent of polymerization was most limited when
      adhesive was not applied (groups 1 and 2), or when ELC was only light cured,
      while V was allowed to auto-cure (group 3). With the one-shot polymerization of
      ELC and V (group 5), the extent of polymerization was similar to the procedure
      involving separate irradiation of adhesive and cement (group 4). The one-shot
      technique was significantly more effective if EDSC was used (group 6).
      CONCLUSION: The use of a self-activating dual-curing adhesive system in
      combination with a dual-curing cement enables effective luting of FRC posts
      regardless of the amount of light transmitted through the post.

PMID- 21734977
TI  - Bonding durability of dual-curing composite core material with different self
      etching adhesive systems in a model complete vertical root fracture
      reconstruction.
AB  - PURPOSE: This study evaluated a dual-curing composite along with different dentin
      adhesive systems for 1 year under water storage, as a new bonding method of root
      fragments in complete vertical root fracture. MATERIALS AND METHODS: Bovine root
      fragments were bonded with the dual-curing resin composite Clearfil DC Core
      Automix (DCA) and one of three adhesive systems: two-step self-etching adhesive
      Clearfil SE Bond (SE), one-step self-etching adhesive Tokuyama Bond Force (BF),
      one-step dual-curing self-etching adhesive Clearfil DC Bond (DC). Microtensile
      bond strength (uTBS)/ultimate tensile bond strength (UTS), FE-SEM ultramorphology
      of fracture modes, and adhesive dentin interface were observed after water
      storage for periods of up to one year. The data were analyzed with two-way ANOVA.
      RESULTS: uTBS was influenced by "dentin adhesive system" (F = 324.455, p < 0.001)
      and "length of water storage" (F = 8.470, p < 0.001). SE yielded significantly
      higher uTBS, regardless of storage period (p < 0.05) and maintained the initial
      uTBS without a significant change after 1 year of water storage (p > 0.05). From
      24 h to 1 month, BF showed significantly higher bond strength than DC. UTS of DCA
      was influenced only by the curing mode of the material (F = 5.051, p = 0.027),
      but not by the length of water storage (F = 0.053, p > 0.05). CONCLUSION: Two
      step self-etching adhesive systems and dual-curing composite core material can be
      considered as a suitable bonding method for complete root fractures.

PMID- 21734978
TI  - Flexural strength of four adhesive fixed dental prostheses of composite resin
      reinforced with glass fiber.
AB  - PURPOSE: To evaluate the flexural strength of two fixed dental prosthesis (FDP)
      designs simulating frameworks of adhesive fixed partial prostheses, reinforced or
      not by glass fiber. MATERIALS AND METHODS: Forty specimens, made with composite
      resin, were divided into 4 groups according to the framework design and the
      presence of fiber reinforcement: A1 - occlusal support; A2: occlusal support +
      glass fiber; B1: occlusal and proximal supports; B2: occlusal and proximal
      supports + glass fiber. The specimens were subjected to the three-point bending
      test, and the data were submitted to two-way ANOVA and Tukey's test (5%).
      RESULTS: Group A2 (97.9 +/- 38 N) was statistically significantly different from
      all other experimental groups, presenting a significantly lower mean flexural
      strength. CONCLUSION: The use of glass fibers did not improve the flexural
      strength of composite resin, and designs with occlusal and proximal supports
      presented better results than designs simulating only occlusal support.

PMID- 21734979
TI  - Effect of static and cyclic loading on ceramic laminate veneers adhered to teeth
      with and without aged composite restorations.
AB  - PURPOSE: Existing composite restorations on teeth are often remade prior to the
      cementation of fixed dental prostheses. The aim of this study was to evaluate the
      effect of static and cyclic loading on ceramic laminate veneers adhered to aged
      resin composite restorations. MATERIALS AND METHODS: Eighty sound maxillary
      incisors were collected and randomly divided into four groups: group 1: control
      group, no restorations; group 2: two Class III restorations; group 3: two Class
      IV restorations; group 4: complete composite substrate. Standard composite
      restorations were made using a microhybrid resin composite (Anterior Shine).
      Restored teeth were subjected to thermocycling (6000 cycles). Window preparations
      were made on the labial surface of the teeth for ceramic laminate fabrication
      (Empress II). Teeth were conditioned using an etch-and-rinse system. Existing
      composite restorations representing the aged composites were silica coated
      (CoJet) and silanized (ESPE-Sil). Ceramic laminates were cemented using a bis-GMA
      based cement (Variolink Veneer). The specimens were randomly divided into two
      groups and were subjected to either static (groups 1a, 2a, 3a, 4a) or cyclic
      loading (groups 1b, 2b, 3b, 4b). Failure type and location after loading were
      classified. Data were analyzed using one-way ANOVA and Tukey's test. RESULTS:
      Significantly higher fracture strength was obtained in group 4 (330 +/- 81 N)
      compared to the controls in group 1 (179 +/- 120 N) (one-way ANOVA, p < 0.05).
      Group 1b survived a lower mean number of cyclic loads (672,820 cycles) than teeth
      of groups 2b to 4b (846x103 to 873x103 cycles). Failure type evaluation after the
      fracture test showed predominantly adhesive failures between dentin and cement,
      but after cyclic loading, more cohesive fractures in the ceramic were seen.
      CONCLUSION: Ceramic laminate veneers bonded to conditioned aged composite
      restorations provided favorable results. Surface conditioning of existing
      restorations may eliminate the necessity of removing aged composite restorations.

PMID- 21734980
TI  - Clinical performance of cervical restorations with desensitizing agents: 18-month
      clinical trial.
AB  - PURPOSE: To evaluate the clinical performance and postoperative sensitivity of
      noncarious Class V restorations with and without the use of a potassium oxalate
      based desensitizing agent over a period of 18 months. MATERIALS AND METHODS: One
      hundred forty cervical lesions (40 patients) were selected and randomly divided
      into four groups: group 1 (G1) - teeth restored with the application of a
      potassium oxalate-based desensitizing agent (BisBlock) after acid etching and
      before the application of the adhesive Adper Single Bond 2; group 2 (G2) - teeth
      restored using the same adhesive system used in G1, without the use of any
      desensitizing agent; group 3 (G3) - similar to G1, but using the adhesive One
      Step; group 4 (G4) - similar to G3, but without the application of BisBlock. All
      restorations were evaluated (double blind) after 1 week and 2, 6, 12, and 18
      months according to the modified USPHS criteria. The McNemar and chi-square tests
      were used to analyze the results (p <= 0.05). RESULTS: There were no statistical
      differences between groups restored with or without the use of a desensitizing
      agent for postoperative sensitvity. After 18 months, retention rates proved to be
      statistically significantly lower for One-Step than Adper Single Bond 2.
      CONCLUSION: The use of potassium oxalate-based desensitizing agent did not
      decrease postoperative sensitivity when it was used under composite resin
      restorations.

PMID- 21734981
TI  - Effects of self-curing activator and curing protocol on the bond strength of
      composite core buildups.
AB  - PURPOSE: To determine the effect of the polymerization mode of simplified bonding
      systems and the corresponding core buildup resin composite on the bond strength
      to dentin. MATERIALS AND METHODS: Composite core buildups were bonded to flat
      prepared dentin surfaces of 320 human molars using a two-step etch-and-rinse
      (Excite, ER) and a two-step self-etching (AdheSE, SE) bonding system. Bonding
      systems were used both with and without their respective self-curing activators
      (Excite DSC, ER+SC; AdheSE DC, SE+SC). Six curing protocols for the dual-curing
      composite (MultiCore Flow) were examined: self-curing for 5 min (a); irradiation
      with light from each aspect for 10 s (b), 20 s (c), and 40 s (d); and irradiation
      with light from the occlusal aspect only for 60 s (e) and 120 s (f). Shear bond
      strengths were measured immediately after curing. Additional measurements were
      performed after water storage of the specimens for 24 h at 37 degrees C. These
      specimens had been cured according the curing protocols given in the
      manufacturer's instructions (groups a and d). Failure modes were analyzed using
      scanning electron microscopy. RESULTS: Immediate bond strengths were
      significantly different among the bonding systems (p < 0.001): SE > ER > ER+SC >
      SE+SC. Immediate bond strengths of ER and SE were significantly lower when the
      composite was self-cured (p < 0.05). The use of SC activators reduced the bond
      strength and promoted adhesive failures to dentin. A severe incompatibility
      problem was observed between the composite and SE+SC. CONCLUSION: Dentin bonding
      of dual-curing composite core buildups in combination with simplified bonding
      systems is still unsatisfactory, even when SC activators are employed. For
      adequate bonding to dentin, polymerization of the dual-curing composite should
      always be light initiated.

PMID- 21734982
TI  - An unexpected palladium-catalyzed reaction of 2-alkynylhalobenzene with 2
      alkynylaniline: a novel and efficient route to 11H-indeno[1,2-c]quinolin-11-ols.
AB  - An unexpected palladium-catalyzed cascade reaction of 2-alkynylhalobenzene with 2
      alkynylaniline is reported, which provides a novel and efficient pathway for the
      synthesis of 11H-indeno[1,2-c]quinolin-11-ols.

PMID- 21734983
TI  - DNA tracking within a nanochannel: device fabrication and experiments.
AB  - Fabrication of nanochannels is drawing considerable interest due to its broad
      applications in nanobiotechnology (e.g. biomolecular sensing and single DNA
      manipulation). Nanochannels offer distinct advantages in allowing a slower
      translocation and multiple sensing spots along the channel, both of which improve
      the read-out resolution. However, implementing electrodes inside the nanochannel
      has rarely been demonstrated to our knowledge. The device described in this work
      is a Si-Glass anodically bonded Lab-on-a-Chip (LOC) device of a few millimetres
      in size capable of performing DNA manipulation. The LOC device structure is based
      on two mainstream microchannels interconnected by nanochannels. DNA, once trapped
      within the nanochannel, has been tracked throughout the length of the channel and
      the data have been recorded and analysed.

PMID- 21734984
TI  - Towards universal enrichment nanocoating for IR-ATR waveguides.
AB  - Polymer multilayered nanocoating capable of concentrating various chemical
      substances at IR-ATR waveguide surfaces is described. The coating affinity to an
      analyte played a pivotal role in sensitivity enhancement of the IR-ATR
      measurements, since the unmodified waveguide did not show any analyte detection.

PMID- 21734985
TI  - Automated solid phase synthesis of teichoic acids.
AB  - This communication describes the first automated solid phase synthesis of
      teichoic acids (TAs) and the preparation by this method of a number of well
      defined TA structures, which were probed for their antigenicity. An
      opsonophagocytic killing assay revealed a clear TA-length-activity relationship
      and indicated a promising candidate for future vaccine development.

PMID- 21734986
TI  - A self-heating cartridge for molecular diagnostics.
AB  - A disposable, water-activated, self-heating, easy-to-use, polymeric cartridge for
      isothermal nucleic acid amplification and visual fluorescent detection of the
      amplification products is described. The device is self-contained and does not
      require any special instruments to operate. The cartridge integrates chemical,
      water-triggered, exothermic heating with temperature regulation facilitated with
      a phase-change material (PCM) and isothermal nucleic acid amplification. The
      water flows into the exothermic reactor by wicking through a porous paper. The
      porous paper's characteristics control the rate of water supply, which in turn
      controls the rate of exothermic reaction. The PCM material enables the cartridge
      to maintain a desired temperature independent of ambient temperatures in the
      range between 20  degrees C and 40  degrees C. The utility of the cartridge is
      demonstrated by amplifying and detecting Escherichia coli DNA with loop mediated
      isothermal amplification (LAMP). The device can detect consistently as few as 10
      target molecules in the sample. With proper modifications, the cartridge also can
      work with other isothermal nucleic acid amplification technologies for detecting
      nucleic acids associated with various pathogens borne in blood, saliva, urine,
      and other body fluids as well as in water and food. The device is suitable for
      use at home, in the field, and in poor-resource settings, where access to
      sophisticated laboratories is impractical, unaffordable, or nonexistent.

PMID- 21734987
TI  - Direct detection of native proteins in biological matrices using extractive
      electrospray ionization mass spectrometry.
AB  - The high-throughput and sensitive characterization of native proteins in
      biological samples is of increasing interest in multiple disciplines. Extractive
      electrospray ionization (EESI) forms ions of native proteins including lysozyme,
      alpha-chymotrypsin, myoglobin, human serum albumin, RNAse A and blood hemoglobin
      in extremely complex biosamples or PBS buffer solutions by softly depositing
      charges on the protein molecules. This method produces no significant
      conformational changes of the proteins in the ion formation process, and features
      direct detection of trace proteins present in biological matrices. The detection
      limit of low pmol L(-1) for lysozyme in untreated biological liquids such as
      human urine and tears was demonstrated using EESI mass spectrometry (MS), showing
      an attractive MS platform for the direct analysis of native proteins in actual
      biological samples.

PMID- 21734988
TI  - Nanostructured MnO2: an efficient and robust water oxidation catalyst.
AB  - Nanostructured MnO(2) exhibits a high turnover frequency for oxygen evolution
      under visible light and high stability in strong acidic conditions.

PMID- 21734989
TI  - Synthesis of ultra-long hollow chalcogenide nanofibers.
AB  - Electrospinning and galvanic displacement reaction are combined to fabricate
      ultra-long hollow chalcogen and chalcogenide nanofibers in a cost-effective and
      high throughput manner. This procedure exploits electrospinning to fabricate
      ultra-long sacrificial nanofibers with controlled dimensions and morphology,
      thereby imparting control over the composition and shape of the nanostructures
      evolved during galvanic displacement reaction. It is believed to be a general
      route to form various ultra-long hollow semiconducting nanofibers.

PMID- 21734990
TI  - Assembly of a family of mixed metal {Mo:V} polyoxometalates templated by TeO3(2
      ): {Mo12V12Te3}, {Mo12V12Te2} and {Mo17V8Te}.
AB  - The influence of the pyramidal heteroanion, TeO(3)(2-) in the self-assembly of
      mixed metal (Mo/V) systems, is demonstrated by the isolation of three novel mixed
      metal, mixed-valence architectures, {Mo(12)V(12)Te(3)} (1), {Mo(12)V(12)Te(2)}
      (2) and {Mo(17)V(8)Te} (3) with the tellurium centres exhibiting the novel MU(8)
      TeO(4) and MU(9)-TeO(3) coordination modes while compounds 1 and 2 were
      discovered utilizing ESI mass spectrometry.

PMID- 21734991
TI  - Analysis of the key intermediates of RDX (hexahydro-1,3,5-trinitro-1,3,5
      triazine) in groundwater: occurrence, stability and preservation.
AB  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a widely used explosive that is
      present in soils at a number of military sites, including training and testing
      ranges. Because of its relatively weak adsorption to soil, RDX frequently
      migrates through the unsaturated zone and causes groundwater contamination. In
      the environment, RDX can transform to produce mono-, di-, and tri-nitroso
      derivatives (MNX, DNX, and TNX) and the ring cleavage products
      methylenedinitramine (MEDINA) and 4-nitro-2,4-diazabutanal (NDAB). The present
      study was undertaken to analyze RDX and its products in groundwater samples taken
      from various US military sites. The stability of some of the common
      transformation intermediates of RDX, including the nitroso derivatives, NDAB and
      MEDINA, under typical conditions in a groundwater aquifer is not well understood,
      and appropriate preservation methods for these compounds have not been
      established. Therefore, we studied the inherent stability of these compounds in
      deionized water and in groundwater, and evaluated various preservation
      techniques, including adjustment of pH, temperature, and salinity. NDAB and
      nitroso derivatives were stable under typical ambient environmental conditions,
      but MEDINA was highly unstable. The addition of sea salts (10% w/v) was found to
      stabilize MEDINA when the samples were stored at 4  degrees C. Using appropriate
      preservation techniques, we detected nitroso derivatives and NDAB, but no MEDINA,
      at some of the sites investigated. Stabilizing RDX intermediate products in field
      samples to allow detection is important because the presence of any of these
      chemicals can indicate past contamination by RDX and provide insight into the
      occurrence of in situ natural attenuation.

PMID- 21734992
TI  - A non-adiabatic quantum-classical dynamics study of the intramolecular excited
      state hydrogen transfer in ortho-nitrobenzaldehyde.
AB  - Ab initio surface-hopping dynamics calculations have been performed to simulate
      the intramolecular excited state hydrogen transfer dynamics of ortho
      nitrobenzaldehyde (o-NBA) in the gas phase from the electronic S(1) excited
      state. Upon UV excitation, the hydrogen is transferred from the aldehyde
      substituent to the nitro group, generating o-nitrosobenzoic acid through a ketene
      intermediate. The semiclassical propagations show that the deactivation from the
      S(1) is ultrafast, in agreement with the experimental measurements, which detect
      the ketene in less than 400 fs. The trajectories show that the deactivation
      mechanism involves two different conical intersections. The first one, a planar
      configuration with the hydrogen partially transferred, is responsible for the
      branching between the formation of a biradical intermediate and the regeneration
      of the starting material. The conversion of the biradical to the ketene
      corresponds to the passage through a second intersection region in which the
      ketene group is formed.

PMID- 21734993
TI  - Labeling DNA for single-molecule experiments: methods of labeling internal
      specific sequences on double-stranded DNA.
AB  - This review is a practical guide for experimentalists interested in specifically
      labeling internal sequences on double-stranded (ds) DNA molecules for single
      molecule experiments. We describe six labeling approaches demonstrated in a
      single-molecule context and discuss the merits and drawbacks of each approach
      with particular attention to the amount of specialized training and reagents
      required. By evaluating each approach according to criteria relevant to single
      molecule experiments, including labeling yield and compatibility with cofactors
      such as Mg(2+), we provide a simple reference for selecting a labeling method for
      given experimental constraints. Intended for non-specialists seeking accessible
      solutions to DNA labeling challenges, the approaches outlined emphasize
      simplicity, robustness, suitability for use by non-biologists, and utility in
      diverse single-molecule experiments.

PMID- 21734994
TI  - Silver coated aluminium microrods as highly colloidal stable SERS platforms.
AB  - We report on the fabrication of a novel material with the ability to remain in
      solution even under the very demanding conditions required for structural and
      dynamic characterization of biomacromolecule assays. This stability is provided
      by the increase in surface area of a low density material (aluminium) natively
      coated with a very hydrophilic surface composed of aluminium oxide (Al(2)O(3))
      and metallic silver nanoparticles. Additionally, due to the dense collection of
      active hot spots on their surface, this material offers higher levels of SERS
      intensity as compared with the same free and aggregated silver nanoparticles.

PMID- 21734995
TI  - Dynamics of the intermolecular hydrogen bonds in the polymorphs of paracetamol in
      relation to crystal packing and conformational transitions: a variable
      temperature polarized Raman spectroscopy study.
AB  - The properties of the intermolecular hydrogen bonds in the monoclinic (Form I)
      and the orthorhombic (Form II) polymorphs of paracetamol, C(8)H(9)NO(2), have
      been studied by single crystal polarized Raman spectroscopy (40 to 3700 cm(-1))
      in a wide temperature range (5 K < T < 300 K) in relation to the dynamics of
      methyl-groups of the two forms. A detailed analysis of the temperature dependence
      of the wavenumbers, bandwidths and integral intensities of the spectral bands has
      revealed an essential difference between the two polymorphs in the strength and
      ordering of OH...O and NH...O hydrogen bonds. The compression of intermolecular
      hydrogen bonds is interrelated with crystal packing and the dynamics of methyl
      groups. On structural compression of the orthorhombic polymorph on cooling, a
      compromise is to be sought between the shortening of OH...O and NH...O bonds,
      attractive CH...O and repulsive CH...H contacts in the crystal structure. As a
      result of a steric conflict at temperatures below 100 K, N-H...O hydrogen bonds
      become significantly disordered, and an extended intramolecular transition from
      the conformation "staggered" with respect to the C=O bond to the one "staggered"
      with respect to the NH bond is observed. In most of the studied crystals this
      transition was only about 60% complete even at 5 K, but in some of the crystals
      the orientation of all the methyl-groups became staggered with respect to the NH
      bond at low temperatures. This complete transition was coupled to a sharp
      shortening of the OH...O and NH...O hydrogen bonds at <100 K, the appearance of
      new additional positions of the protons in these H-bonds, and a slight
      strengthening of the C-HO bonds formed by methyl-groups. The same conformational
      transition has been observed also in the monoclinic polymorph at T < 80 K. The
      crystal packing in Form I prevents the O-H...O hydrogen bonds from adopting the
      optimum geometry, and they are significantly disordered at all the temperatures,
      especially at <=200 K. The packing of molecules in Form I is also not favourable
      to form C-H...O hydrogen bonds involving methyl-groups. One can conclude from the
      comparison of diffraction and spectroscopic data that the higher stability of
      Form I results not from a larger strength of individual OH...O and NH...O
      hydrogen bonds, but is a cumulative effect: all the hydrogen bonds together
      stabilize the structure of the monoclinic polymorph more than that of the
      orthorhombic polymorph.

PMID- 21734996
TI  - d0 Organometallics in catalysis.

PMID- 21735000
TI  - Water uptake in the hydrophilic poly(3,4-ethylenedioxythiophene):poly(styrene
      sulfonate) solid-contact of all-solid-state polymeric ion-selective electrodes.
AB  - Solid-contact (SC) ion-selective electrodes (ISEs) utilizing thin films of
      poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and
      plasticized poly(vinylchloride) (PVC) have been produced using a spin casting
      procedure. This study was carried out with a view of characterizing this popular
      and well known SC ISE using a series of complementary surface analysis
      techniques. This work revealed that PEDOT:PSS prevents the separation of an
      undesirable water layer at the buried interface of this SC ISE due to the high
      miscibility of water in the hydrophilic PEDOT:PSS layer. The lack of a clearly
      defined and molecularly sharp buried interface prohibits the formation of a
      distinct water layer presumably by eliminating sites that promote the
      accumulation of water. This outcome is important to the chemical sensor community
      since it provides further insights into the compatibility of sensor components in
      SC ISEs.

PMID- 21735001
TI  - Synthesis of a cyclic peptide/protein using the NEXT-A reaction followed by
      cyclization.
AB  - By using the NEXT-A reaction, we introduced a non-natural amino acid at the N
      terminus of a peptide/protein that contained a cysteine unit. The side chain of
      the introduced amino acid spontaneously reacted with the cysteine to afford a
      cyclic peptide/protein.

PMID- 21735002
TI  - Simultaneously photodeposited rhodium metal and oxide nanoparticles promoting
      photocatalytic hydrogen production.
AB  - Photodeposition of a Rh cocatalyst under atmospheric conditions could
      simultaneously provide both Rh metal and oxide nanoparticles on a K(2)Ti(6)O(13)
      photocatalyst, both of which cooperatively promoted the photocatalytic hydrogen
      production from water and methane.

PMID- 21735003
TI  - Adlayers based on molecular platforms of trioxatriangulenium.
AB  - The platform approach for preparation of molecular adlayers with freestanding
      functional groups was extended to systems on the basis of the trioxatriangulenium
      ion. Self-assembled monolayers of these compounds were prepared on Au(111)
      surfaces and characterized by scanning tunneling microscopy, revealing highly
      ordered structures.

PMID- 21735004
TI  - Recent developments in the chemistry of antiaromatic boroles.
AB  - First isolated in 1969, most progress in the chemistry of the antiaromatic 4pi
      electron borole system has been made during the 1980s. However, besides the
      fundamental aspects of the electronic structure and reactivity, boroles have not
      encountered serious research efforts for a rather long timeframe. This is
      somewhat surprising given the fact that boroles feature a unique combination of
      antiaromaticity, strong electrophilicity and unusual electronic properties. It
      was not until 2008 that interest was resparked. Since then, tremendous progress
      has been achieved in this area, particularly with respect to synthetic access,
      structural characterization and reactivity. Various differently substituted
      borole derivatives have been successfully isolated and characterized both in
      solution and in the solid state, which provided a more thorough understanding of
      the structure/reactivity relationship. This feature article is intended to
      provide a general overview on the electronic structure and the consequences of
      antiaromaticity on the inherent properties of these highly reactive species. The
      different synthetic methodologies to generate boroles and their divergent
      reactivity patterns will be described in great detail, which will emphasize their
      high potential and relevance in modern chemistry.

PMID- 21735005
TI  - New insight on 2-naphthylmethyl (NAP) ether as a protecting group in carbohydrate
      synthesis: a divergent approach towards a high-mannose type oligosaccharide
      library.
AB  - A new method for selective cleavage of 2-naphthylmethyl (NAP) ether utilizing 10
      20 molar excess of HF/pyridine in toluene was revealed and strategically applied
      to a divergent approach towards generation of a high-mannose type oligosaccharide
      library.

PMID- 21735006
TI  - Interaction between NO and Na, O, S, Cl on Au and Pd(111) surfaces.
AB  - NO co-adsorption with X (X = Na, O, S, and Cl) on Au and Pd(111) surfaces is
      studied using density functional theory (DFT) calculations to get a deeper
      insight into the extraordinary sulfur enhanced adsorption on the Au surface. It
      is found that both electronegative and electropositive adatoms can enhance NO
      adsorption on Au(111). In Na + NO/Au(111), the strong electrostatic attraction
      between Na and NO dominates and stabilizes NO adsorption, though Na-induced
      surface negative charging weakens NO adsorption. In (O, S, Cl) + NO/Au, the
      electronegative atoms would induce a slight surface distortion and enhance NO
      adsorption accordingly. NO adsorption on Pd(111) is enhanced by Na, but weakened
      by electronegative species. We suggest that the unique features of noble metals,
      i.e., the narrow DOS at the Fermi level (E(F)) and the deep buried d-band center,
      should play an important role in the promotion of NO adsorption on their surface
      as the CO case.

PMID- 21735007
TI  - Oligomeric allyl-palladium(II) complexes of beta-substituted ethylselenolates:
      syntheses, structures and thermal decomposition.
AB  - Tri-nuclear allyl-palladium complexes, [Pd(MU-SeCH(2)CH(2)COOR)(eta(3)
      C(3)H(4)R')](3) (R = H, Me, Et and R' = H, Me), have been synthesized by the
      reaction of [Pd(2)(MU-Cl)(2)(eta(3)-C(3)H(4)R')(2)] with NaSeCH(2)CH(2)COOR.
      These complexes exist in a dynamic equilibrium with a dimeric form in solution
      and are fluxional at room temperature as shown by variable temperature (1)H NMR
      spectroscopy. The DFT calculations indicate that there is a negligible energy
      difference between the dimer and the trimer, and suggest that the delicate
      balance between the steric factors and angular strain decides the reaction
      products. These complexes (with R' = H) on treatment with [Pd(2)(MU-Cl)(2)(eta(3)
      C(3)H(5))(2)] afforded hetero-bridged complexes [Pd(2)(MU-Cl)(MU
      SeCH(2)CH(2)COOR)(eta(3)-C(3)H(5))(2)] (R = Me, Et). All the complexes have been
      characterized by NMR ((1)H, (13)C, (77)Se) spectroscopy. The molecular structure
      of [Pd(MU-SeCH(2)CH(2)COOEt)(eta(3)-C(3)H(5))](3) revealed a chair conformation
      of the six-membered Pd(3)Se(3) ring, in which all the allyl groups lie at one
      side of the ring (similar to three axial 1,3,5-hydrogens of cyclohexane).
      Thermolysis of [Pd(MU-SeCH(2)CH(2)COOEt)(eta(3)-C(3)H(5))](n) in diphenyl ether
      or hexadecylamine (HDA) yielded Pd(7)Se(4) as characterized by powder XRD.

PMID- 21735008
TI  - The synthesis and photophysics of tris-heteroleptic cyclometalated iridium
      complexes.
AB  - Herein we report the synthesis and photophysical study of tris-heteroleptic
      complexes of the general formula IrLL'(acac), where L and L' are two differently
      substituted 2-phenylpyridines (ppyH) and acacH is 2,4-pentanedione, using a
      combinatorial approach that could be employed for many ligand combinations. The
      tris-heteroleptic complexes and the analogous bis-heteroleptic complexes of the
      form IrL(2)(acac) have been studied by a combination of absorption and
      photoluminescence spectroscopies in conjunction with modelling by DFT and TD-DFT
      to elucidate the nature and location of the excited state in the novel species.

PMID- 21735009
TI  - 2-phenyl-4-bis(methylthio)methyleneoxazol-5-one: versatile template for diversity
      oriented synthesis of heterocycles.
AB  - 4-Bis(methylthio)methylene-2-phenyloxazol-5-one (1) has been shown to be a
      versatile template for the synthesis of novel heterocyclic scaffolds. The key
      protocol involves nucleophilic ring opening of 1 with various primary aliphatic,
      aromatic amines and diamines to give open-chain amide adducts which are
      transformed into 4-bis(methylthio)methylene-2-phenyl-1-alkyl/arylimidazol-5-(4H)
      ones (5) in good yields in the presence of anhydrous NaOAc/AcOH. Similarly, the
      amide adducts 4h-i from 3,4-dimethoxyphenylethylamine and tryptamine undergo
      interesting rearrangement in the presence of POCl(3) to furnish 1-(2-phenyl-5
      methylthio-4-thiazolyl)dihydroisoquinoline and beta-carboline derivatives 8-9 in
      good yields. The amide adduct 14 from o-phenylenediamine on exposure to refluxing
      acetic acid or in the presence of Ag(2)CO(3) affords substituted 3H-1,5
      benzodiazepinone, 2-(5-methylthio-2-phenyl-4-oxazolyl)-1H-benzimidazole and
      trisubstituted oxazole (15-17), whereas the bis-adduct from ethylenediamine
      yields ethylene bridge tethered bis-imidazole 23 and bis-oxazole 24 under similar
      reaction conditions. Probable mechanisms for the formation of various products
      have been suggested.

PMID- 21735010
TI  - Weak interactions in the assembly of strongly chemisorbed molecules.
AB  - The intermolecular structure of bimolecular complexes formed on Pt(111) at room
      temperature through CH...O interactions between 1-methylnaphthalene or 1
      ethylnaphthalene and 2,2,2-trifluoroacetophenone is directed by the partial
      dehydrogenation of the alkyl groups.

PMID- 21735011
TI  - Graphene oxide as an electrophile for carbon nucleophiles.
AB  - The covalent, surface functionalization of graphene oxide with the malononitrile
      anion has been demonstrated. Once installed, these surface-bound "molecular
      lynchpins" can be chemically modified to increase the solubility of the graphene
      derivative in either organic or aqueous environments.

PMID- 21735012
TI  - Li3V2(PO4)3/graphene nanocomposites as cathode material for lithium ion
      batteries.
AB  - Li(3)V(2)(PO(4))(3)/graphene nanocomposites have been firstly formed on reduced
      graphene sheets as cathode material for lithium batteries. The nanocomposites
      synthesized by the sol-gel process exhibit excellent high-rate and cycling
      stability performance, owing to the nanoparticles connected with a current
      collector through the conducting graphene network.

PMID- 21735013
TI  - A photoinduced pH jump applied to drug release from cucurbit[7]uril.
AB  - A proof-of-principle for the application of a photoinduced pH jump for delivery
      of the Hoechst 33258 drug by disassembly of its host-guest complex with
      cucurbit[7]uril is described.

PMID- 21735014
TI  - A pyrene-based fluorescent sensor for Zn2+ ions: a molecular 'butterfly'.
AB  - A simple pyrene-based triazole receptor has been synthesised and shown to self
      assemble in the presence of ZnCl(2) in an exclusively 2:1 ratio, whereas a
      mixture of 2:1 and 1:1 ratios are observed for other Zn(2+) salts. The pyrene
      units are syn in orientation; this is supported by a strong excimer signal
      observed at 410 nm in the presence of ZnCl(2) in acetonitrile. DFT calculations
      and 2D NMR support the proposed structure.

PMID- 21735015
TI  - Coordination of two different metal ions as reason for N-chirality in MU-amide
      complexes.
AB  - The primary amine MeNH(2), when bonded to Pt(II), is converted into a methylamide
      bridge upon coordination of a second, different metal ion (Pd(II)), thereby
      making the N atom chiral.

PMID- 21735016
TI  - Imine-assisted C-F bond activation by electron-rich iron complexes supported by
      trimethylphosphine.
AB  - C-F bond activation of ortho-fluorinated benzalimines 2,6-F(2)C(6)R1R2R3-CH=N-R
      (1-3) using the electron-rich complex Fe(PMe(3))(4) is reported. With the
      assistance of the imine group as the anchoring group, bis-chelated iron(II)
      complexes (C(6)FR1R2R3-CH=N-R)(2)Fe(PMe(3))(2) (4-6) were formed. The reaction of
      2,6-difluorobenzylidenenaphthalen-1-amine 2,6-F(2)C(6)H(3)-CH=N-C(10)H(7) (9)
      with Fe(PMe(3))(4) affords [CNC]-pincer iron(II) complex (C(6)H(3)F-CH=N
      C(10)H(6))Fe(PMe(3))(3) (10) through both C-F and C-H bond activation and pi
      (C=N) coordinate iron(0) complex (C(6)H(3)F-CH=N-C(10)H(7))(2)Fe(PMe(3))(2) (11)
      with C,C-coupling, while a similar reaction with perfluorobenzylidenenaphthalen-1
      amine C(6)F(5)-CH=N-C(10)H(7) (14) gave rise to only [CNC]-pincer iron(II)
      complex (C(6)F(4)-CH=N-C(10)H(6))Fe(PMe(3))(3) (15). The proposed formation
      mechanisms of these complexes are discussed. The structures of complexes 5, 6, 10
      and 11 were confirmed by X-ray single crystal diffraction.

PMID- 21735017
TI  - Global risk transformative prioritization for prostate cancer candidate genes in
      molecular networks.
AB  - Understanding the pathogenesis of complex diseases is aided by precise
      identification of the genes responsible. Many computational methods have been
      developed to prioritize candidate disease genes, but coverage of functional
      annotations may be a limiting factor for most of these methods. Here, we
      introduce a global candidate gene prioritization approach that considers
      information about network properties in the human protein interaction network and
      risk transformative contents from known disease genes. Global risk transformative
      scores were then used to prioritize candidate genes. This method was introduced
      to prioritize candidate genes for prostate cancer. The effectiveness of our
      global risk transformative algorithm for prioritizing candidate genes was
      evaluated according to validation studies. Compared with ToppGene and random walk
      based methods, our method outperformed the two other candidate gene
      prioritization methods. The generality of our method was assessed by testing it
      on prostate cancer and other types of cancer. The performance was evaluated using
      standard leave-one-out cross-validation.

PMID- 21735018
TI  - Singlet molecular oxygen trapping by the fluorescent probe diethyl-3,3'-(9,10
      anthracenediyl)bisacrylate synthesized by the Heck reaction.
AB  - Singlet molecular oxygen O(2)((1)Delta(g)) is a potent oxidant that can react
      with different biomolecules, including DNA, lipids and proteins. Many polycyclic
      aromatic hydrocarbons have been studied as O(2)((1)Delta(g)) chemical traps.
      Nevertheless, a suitable modification in the polycyclic aromatic ring must be
      made to increase the yield of O(2)((1)Delta(g)) chemical trapping. With this
      goal, an anthracene derivative, diethyl-3,3'-(9,10-anthracenediyl)bisacrylate
      (DADB), was obtained from the reaction of 9,10-dibromoanthracene and ethyl
      acrylate through the Heck coupling reaction. The coupling of ethyl acrylate with
      the anthracene ring produced a new lipophilic, esterified, fluorescent probe
      reactive toward O(2)((1)Delta(g)). This compound reacts with O(2)((1)Delta(g)) at
      a rate of k(r) = 1.69 * 10(6) M(-1) s(-1) forming a stable endoperoxide
      (DADBO(2)), which was characterized by UV-Vis, fluorescence, HPLC/MS and (1)H and
      (13)C NMR techniques. The photophysical, photochemical and thermostability
      features of DADB were also evaluated. Furthermore, this compound has the
      potential for great application in biological systems because it is easily
      synthetized in large amount and generates specific endoperoxide (DADBO(2)), which
      can be easily detected by HPLC tandem mass spectrometry (HPLC/MS/MS).

PMID- 21735019
TI  - Oxidation mechanism of diethyl ether: a complex process for a simple molecule.
AB  - A large number of organic compounds, such as ethers, spontaneously form unstable
      peroxides through a self-propagating process of autoxidation (peroxidation).
      Although the hazards of organic peroxides are well known, the oxidation
      mechanisms of peroxidizable compounds like ethers reported in the literature are
      vague and often based on old experiments, carried out in very different
      conditions (e.g. atmospheric, combustion). With the aim to (partially) fill the
      lack of information, in this paper we present an extensive Density Functional
      Theory (DFT) study of autoxidation reaction of diethyl ether (DEE), a chemical
      that is largely used as solvent in laboratories, and which is considered to be
      responsible for various accidents. The aim of the work is to investigate the most
      probable reaction paths involved in the autoxidation process and to identify all
      potential hazardous intermediates, such as peroxides. Beyond the determination of
      a complex oxidation mechanism for such a simple molecule, our results suggest
      that the two main reaction channels open in solution are the direct decomposition
      (beta-scission) of DEE radical issued of the initiation step and the
      isomerization of the peroxy radical formed upon oxygen attack (DEEOO). A simple
      kinetic evaluation of these two competing reaction channels hints that radical
      isomerization may play an unexpectedly important role in the global DEE oxidation
      process. Finally industrial hazards could be related to the hydroperoxide
      formation and accumulation during the chain propagation step. The resulting
      information may contribute to the understanding of the accidental risks
      associated with the use of diethyl ether.

PMID- 21735020
TI  - Oxygen evolving complex in photosystem II: better than excellent.
AB  - The Oxygen Evolving Complex in photosystem II, which is responsible for the
      oxidation of water to oxygen in plants, algae and cyanobacteria, contains a
      cluster of one calcium and four manganese atoms. This cluster serves as a model
      for the splitting of water by energy obtained from sunlight. The recent published
      data on the mechanism and the structure of photosystem II provide a detailed
      architecture of the oxygen-evolving complex and the surrounding amino acids.
      Biomimetically, we expect to learn some strategies from this natural system to
      synthesize an efficient catalyst for water oxidation, that is necessary for
      artificial photosynthesis.

PMID- 21735021
TI  - Forward-backward semiclassical and quantum trajectory methods for time
      correlation functions.
AB  - Forward-backward trajectory formulations of time correlation functions are
      reviewed. Combination of the forward and reverse time evolution operators within
      the time-dependent semiclassical approximation minimizes phase cancellation,
      giving rise to an efficient methodology for simulating the dynamics of low
      temperature fluids. A quantum mechanical version of the forward-backward
      formulation, based on the hydrodynamic formulation of time-dependent quantum
      mechanics, is also available but is practical only for small systems.

PMID- 21735022
TI  - Homoleptic ruthenium(III) chalcogenolates: a single precursor to metal
      chalcogenide nanoparticles catalyst.
AB  - Eight homoleptic metal(III) arylchalcogenolate polymers [M(EPh-p-X)(3)](n) (M =
      Ru, Cr, and Mo) were characterized by PXRD. Structural solution of [Ru(SPh-p
      tBu)(3)](n)1 was achieved by Rietveld refinement of the PXRD data. Pyrolysis of
      [Ru(SePh)(3)](n)4 produced nanostructured RuSe(2), which selectively catalyzed
      the reduction of nitro compounds in the presence of other functionalities.

PMID- 21735023
TI  - Introducing an amine functionality at the block junction of amphiphilic block
      copolymers by anionic polymerization strategies.
AB  - A series of block copolymers bearing a single amino in-chain functionality was
      synthesized via anionic polymerization of styrene and ethylene oxide. By means of
      both a conventional and a continuous setup, living polystyrene was quantitatively
      end functionalized with an oxirane (DBAG) prior to the polymerization of the
      poly(ethylene oxide) segment. The in-chain amine was conjugated with a
      fluorescent dye.

PMID- 21735024
TI  - Modular peripheral functionalization of thiophene dendrons and dendrimers.
AB  - A series of thiophene dendrons and dendrimers with peripheral functional groups
      were designed and synthesized. Two methodologies using thiophene dendrons and
      dendrons as synthetic building blocks, namely, (1) periphery functionalization;
      (2) a combination of focal and periphery functionalization have been
      demonstrated.

PMID- 21735025
TI  - Computing charge-exchange cross sections for Ca+ collisions with Rb at low and
      ultralow energies.
AB  - Collisions between Ca cations and Rb atoms are computed within a quantum approach
      that generates the most relevant potential energy curves from accurate ab initio
      methods and carries out the low-energy scattering calculations by including
      nonadiabatic and spin-orbit coupling terms. The cross sections are obtained at
      relative energies typical for the likely arrangements of Rb atoms in a Magneto
      Optical Trap overlapped with a Coulomb Crystal of Ca cations. The dominant
      nonadiabatic process is clearly identified and the efficiency of the nonadiabatic
      coupling terms which lead to the charge-exchange process is discussed.

PMID- 21735026
TI  - Excitons in semiconducting carbon nanotubes: diameter-dependent photoluminescence
      spectra.
AB  - Semiconducting single-walled carbon nanotubes are one-dimensional (1D) quantum
      nanostructures and their unique optical responses arise from stable 1D excitons
      with huge binding energies. Here we review recent studies on optical properties
      of semiconducting carbon nanotubes. The diameter dependence of luminescence
      spectra and dynamics are revealed by single-nanotube spectroscopy and time
      resolved optical spectroscopy. Short-range Coulomb interactions play a crucial
      role in energy structures of dark, triplet, and charged excitons. Enhanced
      exciton-exciton interactions in 1D semiconductor nanostructures determine
      nonlinear optical responses. We present generic configurations of neutral and
      charged excitons and discuss exciton optics of single-walled carbon nanotubes.

PMID- 21735027
TI  - Fabrication of Co3O4-reduced graphene oxide scrolls for high-performance
      supercapacitor electrodes.
AB  - A new type of scrolled structure of Co(3)O(4)/reduced graphene oxide (r-GO) is
      facilely prepared through a two-step surfactant-assisted method. This assembly
      enables almost every single Co(3)O(4) scroll to connect with the r-GO platelets,
      thus leading to remarkable electrochemical performances in terms of high specific
      capacitance and good rate capability.

PMID- 21735028
TI  - Antibody-functionalized SERS tags with improved sensitivity.
AB  - Protein detection at the femtomolar level can be achieved by using metallic
      nanoparticle assemblies that function as surface enhanced Raman spectroscopy
      reporters and that contain suitable surface-bound recognition elements. Proper
      control of the interaction between nanoparticles within the assemblies is
      critical for achieving this performance.

PMID- 21735029
TI  - Extraction separation of rare-earth ions via competitive ligand complexations
      between aqueous and ionic-liquid phases.
AB  - The extraction separation of rare earth elements is one of the most challenging
      separation processes in hydrometallurgy and advanced nuclear fuel cycles. The
      TALSPEAK process (trivalent actinide lanthanide separations by phosphorus-reagent
      extraction from aqueous komplexes) is a prime example of these separation
      processes. The objective of this paper is to explore the use of ionic liquids
      (ILs) for the TALSPEAK-like process, to further enhance its extraction
      efficiencies for lanthanides, and to investigate the potential of using this
      modified TALSPEAK process for separation of lanthanides among themselves. Eight
      imidazolium ILs ([C(n)mim][NTf(2)] and [C(n)mim][BETI], n = 4,6,8,10) and one
      pyrrolidinium IL ([C(4)mPy][NTf(2)]) were investigated as diluents using di(2
      ethylhexyl)phosphoric acid (HDEHP) as an extractant for the separation of
      lanthanide ions from aqueous solutions of 50 mM glycolic acid or citric acid and
      5 mM diethylenetriamine pentaacetic acid (DTPA). The extraction efficiencies were
      studied in comparison with diisopropylbenzene (DIPB), an organic solvent used as
      a diluent for the conventional TALSPEAK extraction system. Excellent extraction
      efficiencies and selectivities were found for a number of lanthanide ions using
      HDEHP as an extractant in these ILs. The effects of different alkyl chain lengths
      in the cations of ILs and of different anions on extraction efficiencies and
      selectivities of lanthanide ions are also presented in this paper.

PMID- 21735030
TI  - 'Fab-chips': a versatile, fabric-based platform for low-cost, rapid and
      multiplexed diagnostics.
AB  - Low cost and scalable manufacture of lab-on-chip devices for applications such as
      point-of-care testing is an urgent need. Weaving is presented as a unified,
      scalable and low-cost platform for the manufacture of fabric chips that can be
      used to perform such testing. Silk yarns with different properties are first
      selected, treated with the appropriate reagent solutions, dried and handloom
      woven in one step into an integrated fabric chip. This platform has the unique
      advantage of scaling up production using existing and low cost physical
      infrastructure. We have demonstrated the ability to create pre-defined flow paths
      in fabric by using wetting and non-wetting silk yarns and a Jacquard attachment
      in the loom. Further, we show that yarn parameters such as the yarn twist
      frequency and weaving coverage area may be conveniently used to tune both the
      wicking rate and the absorptive capacity of the fabric. Yarns optimized for their
      final function were used to create an integrated fabric chip containing reagent
      coated yarns. Strips of this fabric were then used to perform a proof-of-concept
      immunoassay with sample flow taking place by capillary action and detection being
      performed by a visual readout.

PMID- 21735031
TI  - Redox-driven sulfate ion transfer between two tripodal tris(urea) receptors.
AB  - Two anion receptors with the same tripodal scaffold but different signaling
      groups are employed to control intermolecular anion transfer via an
      electrochemical stimulus, which is detected by the change of the fluorescence
      intensity before and after electrochemical oxidation of the ferrocenyl units.

PMID- 21735032
TI  - Biomimetic peptide bond formation in water with aminoacyl phosphate esters.
AB  - Aminoacyl phosphates, biomimetic analogues of aminoacyl adenylates, react
      efficiently with amino acid esters to form dipeptides with retention of
      stereochemical integrity. The reactions are selective and occur readily in the
      presence of nucleophiles other than amino groups on their side chains. Aminoacyl
      phosphate esters that lack an amino-protecting group are also suitable for
      peptide bond formation, leading to a simplified overall process.

PMID- 21735037
TI  - Structures, spectroscopic properties and redox potentials of quaterpyridyl Ru(II)
      photosensitizer and its derivatives for solar energy cell: a density functional
      study.
AB  - Scalar relativistic density functional theory (DFT) has been used to explore the
      spectroscopic and redox properties of Ruthenium-type photovoltaic sensitizers,
      trans-[Ru((R)L)(NCS)(2)] ((R)L = 4,4'''-di-R-4',4''-bis(carboxylic acid)-2,2' :
      6',2'' : 6'',2'''-quaterpyridine, R = H (1), Me (2), (t)Bu (3) and COOH (4); (R)L
      = 4,4'''-di-R-4',4''-bis(carboxylic acid)-cycloquaterpyridine, R = COOH (5)). The
      geometries of the molecular ground, univalent cationic and triplet excited states
      of 1-5 were optimized. In complexes 1-4, the quaterpyridine ligand retains its
      planarity in the molecular, cationic and excited states, although the C=N-Ru
      angle representing the SCN -> Ru coordination approaches 180 degrees  in the
      univalent cationic and triplet excited states. The theoretically designed complex
      5 displays a curved cycloquaterpyridine ligand with significantly distorted SCN 
      > Ru coordination. The electron spin density distributions reveal that one
      electron is removed from the Ru/NCS moieties upon oxidation and the triplet
      excited state is due to the Ru/NCS -> polypyridine charge transfer (MLCT/L'LCT).
      The experimental absorption spectra were well reproduced by the time-dependent
      DFT calculations. In the visible region, two MLCT/L'LCT absorption bands were
      calculated to be at 652 and 506 nm for 3, agreeing with experimental values of
      637 and 515 nm, respectively. The replacement of the R- group with -COOH
      stabilizes the lower-energy unoccupied orbitals of pi* character in the
      quaterpyridine ligand in 4. This results in a large red shift for these two
      MLCT/L'LCT bands. In contrast, the lower-energy MLCT/L'LCT peak of 5 nearly
      disappears due to the introduction of cycloquaterpyridine ligand. The higher
      energy bands in 5 however become broader and more intense. As far as absorption
      in the visible region is concerned, the theoretically designed 5 may be a very
      promising sensitizer for DSSC. In addition, the redox potentials of 1-5 were
      calculated and discussed, in conjunction with photosensitizers such as cis
      [Ru(L(1))(2)(X)(2)] (L(1) = 4,4'-bis(carboxylic acid)-2,2'-bipyridine; X = NCS(-)
      (6), Cl(-) (7) and CN(-) (8)), cis-[Ru(L(1)')(2)(NCS)(2)] (L(1)' = 4,7
      bis(carboxylic acid)-1,10-phenanthroline, 9), [NH(4)][Ru(L(2))(NCS)(3)] (L(2) =
      4,4',4''-tris(carboxylic acid)-2,2' : 6',2''-terpyridine, 10) and
      [Ru(L(2))(NCS)(3)](-) (11).

PMID- 21735038
TI  - Trapping molecular ions formed via photo-associative ionization of ultracold
      atoms.
AB  - The formation of (40)Ca(2)(+) molecular ions is observed in a hybrid (40)Ca
      magneto-optical and ion trap system. The molecular ion formation process is
      determined to be photo-associative ionization of ultracold (40)Ca atoms. A lower
      bound for the two-body rate constant is found to be beta >= 2 +/- 1 * 10(-15)
      cm(3) Hz. Ab initio molecular potential curves are calculated for the neutral
      Ca(2) and ionic Ca(2)(+) molecules and used in a model that identifies the photo
      associative ionization pathway. As this technique does not require a separate
      photo-association laser, it could find use as a simple, robust method for
      producing ultracold molecular ions.

PMID- 21735039
TI  - Second generation of fucose-based DC-SIGN ligands: affinity improvement and
      specificity versus Langerin.
AB  - DC-SIGN and Langerin are two C-type lectins involved in the initial steps of HIV
      infections: the former acts as a viral attachment factor and facilitates viral
      invasion of the immune system, the latter has a protective effect. Potential
      antiviral compounds targeted against DC-SIGN were synthesized using a common
      fucosylamide anchor. Their DC-SIGN affinity was tested by SPR and found to be
      similar to that of the natural ligand Lewis-X (Le(X)). The compounds were also
      found to be selective for DC-SIGN and to interact only weakly with Langerin.
      These molecules are potentially useful therapeutic tools against sexually
      transmitted HIV infection.

PMID- 21735040
TI  - Sequential congruency effects: disentangling priming and conflict adaptation.
AB  - Responding to the color of a word is slower and less accurate if the word refers
      to a different color (incongruent condition) than if it refers to the same color
      (congruent condition). This phenomenon, known as the Stroop effect, is modulated
      by sequential effects: it is bigger when the current trial is preceded by a
      congruent condition than by an incongruent one in the previous trial. Whether
      this phenomenon is due to priming mechanisms or to cognitive control is still
      debated. To disentangle the contribution of priming with respect to conflict
      adaptation mechanisms in determining sequential effects, two experiments were
      designed here with a four-alternative forced choice (4-AFC) Stroop task: in the
      first one only trials with complete alternations of features were used, while in
      the second experiment all possible types of repetitions were presented. Both
      response times (RTs) and errors were evaluated. Conflict adaptation effects on
      RTs were limited to congruent trials and were exclusively due to priming: they
      disappeared in the priming-free experiment and, in the second experiment, they
      occurred in sequences with feature repetitions but not in complete alternation
      sequences. Error results, instead, support the presence of conflict adaptation
      effects in incongruent trials. In priming-free sequences (experiment 1 and
      complete alternation sequences of experiment 2) with incongruent previous trials
      there was no error Stroop effect, while this effect was significant with
      congruent previous trials. These results indicate that cognitive control may
      modulate performance above and beyond priming effects.

PMID- 21735041
TI  - Involuntary strategy-dependent dual task performance.
AB  - Previous studies showed that some dual tasks can be performed simultaneously
      without costs. Yet, a variable SOA between the inputs to such tasks leads to
      strategic, often involuntary, prioritization of one of the two tasks. Here we
      explore the boundary conditions for this involuntary or exogenous strategy. In
      Experiment 1, subjects were initially trained on dual task performance where the
      input to the two tasks is presented simultaneously (0 SOA). We used two tasks
      that under such conditions can be performed without costs and indeed subjects
      displayed perfect sharing of the tasks. Subjects then performed the same two
      tasks but with a variable SOA (0, 50, 150, 800 ms). This manipulation led to a
      serial-like performance of the two tasks even in trials with 0 SOA. In Experiment
      2, subjects participated in eight sessions. Within each session, they performed
      in alternation blocks with a fixed 0 SOA and blocks with a variable SOA. Subjects
      displayed perfect sharing in the pure 0 SOA blocks but performed the two tasks
      serially in the mixed SOA blocks despite receiving identical instructions. These
      findings demonstrate that task context is a powerful factor in dual task
      performance and may lead subjects to involuntarily exhibit dual task costs even
      in conditions where they can perform the tasks without any costs. Moreover, these
      findings strongly suggest that costs observed in PRP studies reflect the use of
      such exogenous strategies rather than a general structural dual task limitation.

PMID- 21735042
TI  - Searching working memory for the source of dual-task costs.
AB  - Dual-task costs depend on the specific pairings of stimulus and response
      modalities. Such findings are analogous to domain-specific effects in the working
      memory (WM) literature, in which items compete for limited capacity when they
      involve related types of information. The present study explicitly examines the
      relationship between modality-pairing effects on dual-task costs and domain
      specificity effects on WM capacity. Participants maintained a sequence of either
      locations or tones in WM, and then performed a choice reaction time task in which
      they responded either vocally or manually. The stimuli for the choice reaction
      time task were held constant, but its response modality affected the interference
      observed in WM: vocal responses interfered with WM for tones and manual responses
      interfered with WM for locations. These findings indicate that response selection
      engages domain-specific WM processes and that interference within these processes
      may account for modality-pairing effects.

PMID- 21735043
TI  - Linking new and old concepts: inflammation meets the Warburg phenomenon in
      pulmonary arterial hypertension.

PMID- 21735044
TI  - Design and validation of an endothelial progenitor cell capture chip and its
      application in patients with pulmonary arterial hypertension.
AB  - The number of circulating endothelial progenitor cells (EPCs) inversely
      correlates with cardiovascular risk and clinical outcome, and thus has been
      proposed as a valuable biomarker for risk assessment, disease progression, and
      response to therapy. However, current strategies for isolation of these rare
      cells are limited to complex, laborious approaches. The goal of this study was
      the design and validation of a disposable microfluidic platform capable of
      selectively capturing and enumerating EPCs directly from human whole blood in
      healthy and diseased subjects, eliminating sample preprocessing. We then applied
      the "EPC capture chip" clinically and determined EPC numbers in blood from
      patients with pulmonary arterial hypertension (PAH). Blood was collected in tubes
      and injected into polymeric microfluidic chips containing microcolumns pre-coated
      with anti-CD34 antibody. Captured cells were immunofluorescently stained for the
      expression of stem and endothelial antigens, identified and counted. The EPC
      capture chip was validated with conventional flow cytometry counts (r = 0.83).
      The inter- and intra-day reliability of the microfluidic devices was confirmed at
      different time points in triplicates over 1-5 months. In a cohort of 43 patients
      with three forms of PAH (idiopathic/heritable, drug-induced, and connective
      tissue disease), EPC numbers are ~50% lower in PAH subjects vs. matched controls
      and inversely related to two potential disease modifiers: body mass index and
      postmenopausal status. The EPC capture chip (5 * 30 * 0.05 mm(3)) requires only
      200 MUL of human blood and has the strong potential to serve as a rapid bedside
      test for the screening and monitoring of patients with PAH and other
      proliferative cardiovascular, pulmonary, malignant, and neurodegenerative
      diseases.

PMID- 21735045
TI  - Assessing the RNA effect of 26 DNA variants in the BRCA1 and BRCA2 genes.
AB  - Comprehensive genetic testing of the breast cancer susceptibility genes BRCA1 and
      BRCA2 identified approximately 16% of variants of unknown significance (VUS), a
      significant proportion of which could affect the correct splicing of the genes.
      Our aim is to establish a workflow for classifying VUS in these complex genes,
      the first stage of which is splicing analysis. We used a combined approach
      consisting of five in silico splicing prediction programs and RT-PCR analysis for
      a set of 26 variants not previously studied at the mRNA level and six variants
      that had already been studied, four of which were used as positive controls as
      they were found to affect the splicing of these genes and the other two were used
      as negative controls. We identified a splicing defect in 8 of the 26 newly
      studied variants and ruled out splicing alteration in the remaining 18 variants.
      The results for the four positive and the two negative control variants were
      consistent with results presented in the literature. Our results strongly suggest
      that the combination of RNA analysis and in silico programs is an important step
      towards the classification of VUS. The results revealed a very high correlation
      between experimental data and in silico programs when using tools for predicting
      acceptor/donor sites but a lower correlation in the case of tools for identifying
      ESE elements.

PMID- 21735046
TI  - Comparative gene expression analysis in mouse models for identifying critical
      pathways in mammary gland development.
AB  - Functional development of the mammary gland is an important physiological
      process. Several studies have used gene expression profiling of mammary gland
      development to identify the key genes in the process, but few focused on the
      involved pathways. And there is a lack of concordance between those observed
      pathways. In this article, we applied a standardized microarray preprocessing to
      four independent studies, and then used gene set enrichment analysis (GSEA) to
      identify the key pathways. The result demonstrated an increased concordance
      between these expression profiling data sets. From the stage of puberty to
      pregnancy, we found 7 up-regulated and 6 down-regulated pathways in common. From
      the period of pregnancy to lactation, we found 7 up-regulated and 58 down
      regulated pathways in common. And 10 up-regulated and 3 down-regulated pathways
      were found in common from lactation to the involution period. The main canonical
      pathways identified belong to immune system, cell communication, metabolism, and
      disease-related pathways. Pathway analysis is a more effective method than single
      gene analysis because the former one can able to detect genes weakly connected to
      the phenotype. As we applied GSEA to the study, our findings suggested a greater
      concordance in this physiological process. The critical pathways we find can
      provide some insight of functional development of the mammary gland and motivate
      other relative studies.

PMID- 21735047
TI  - A SEER-Medicare population-based study of lymphedema-related claims incidence
      following breast cancer in men.
AB  - Each year there are an estimated 200,000 new breast cancer cases diagnosed in the
      United States; of these, 1% of cases are in men. Lymphedema can be a devastating
      complication from breast cancer and its treatment. Currently, almost all
      lymphedema-related research is based on women and extrapolated to men. We
      conducted the first population-based study of men with incident breast cancer of
      any stage, diagnosed from 1998 to 2005, who were 65 years and older in the
      Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. We
      utilized claims related to lymphedema and lymphedema treatment in our cohort. We
      defined 'lymphedema-specific' claims to contain the word 'lymphedema' in the
      Medicare claim description; similarly, 'lymphedema-related' claims were defined
      as treatments reimbursed for lymphedema but not necessarily containing the word
      'lymphedema' in the Medicare claim description. We identified 628 men with
      incident breast cancer from 1998 to 2005 who were 65 years and older. The
      cumulative incidence, censored for deaths, of lymphedema-specific claims at 2, 3,
      4, and 5 years was 8.0, 9.2, 10.5, and 10.5%, respectively. The median follow-up
      was 3.4 years and for those without any event was 4.7 years. The cumulative
      incidence, censored for deaths, of lymphedema-related claims at 2, 3, 4, and 5
      years was 26.9, 32.2, 35.4, and 39.8%. Rates for men were similar to analogous
      rates for women. Lymphedema is a common complication affecting men with breast
      cancer as well as women and appropriate treatment and rehabilitation strategies
      need to be implemented for both genders.

PMID- 21735048
TI  - [Geriatric patients in emergency and intensive care medicine].
AB  - The democratic shift poses new challenges in emergency medicine and intensive
      care. Old patients call for special needs that have to be taken into
      consideration during treatment. Due to the heterogeneity in this patient group
      biological age plays an important role. Mortality among old patients is high, but
      functionality and comorbidity have a great effect on patient outcome. Structural
      and functional organ changes have an additional impact on the treatment of
      geriatric patients in emergency medicine and intensive care. Therefore, basic
      geriatric knowledge should be part of the curricula of both, intensive care and
      emergency medicine.

PMID- 21735049
TI  - The role of muscles in tension-type headache.
AB  - The tenderness of pericranial myofascial tissues and number of myofascial trigger
      points are considerably increased in patients with tension-type headache (TTH).
      Mechanisms responsible for the increased myofascial pain sensitivity have been
      studied extensively. Peripheral activation or sensitization of myofascial
      nociceptors could play a role in causing increased pain sensitivity, but firm
      evidence for a peripheral abnormality still is lacking. Peripheral mechanisms are
      most likely of major importance in episodic TTH. Sensitization of pain pathways
      in the central nervous system due to prolonged nociceptive stimuli from
      pericranial myofascial tissues seem to be responsible for the conversion of
      episodic to chronic TTH. Treatment directed toward muscular factors include
      electromyography biofeedback, which has a documented effect in patients with TTH,
      as well as physiotherapy and muscle relaxation therapy, which are most likely
      effective. Future studies should aim to identify the source of peripheral
      nociception.

PMID- 21735050
TI  - External validation of bifactor model of ADHD: explaining heterogeneity in
      psychiatric comorbidity, cognitive control, and personality trait profiles within
      DSM-IV ADHD.
AB  - The current paper provides external validation of the bifactor model of ADHD by
      examining associations between ADHD latent factor/profile scores and external
      validation indices. 548 children (321 boys; 302 with ADHD), 6 to 18 years old,
      recruited from the community participated in a comprehensive diagnostic
      procedure. Mothers completed the Child Behavior Checklist, Early Adolescent
      Temperament Questionnaire, and California Q-Sort. Children completed the Stop and
      Trail-Making Task. Specific inattention was associated with
      depression/withdrawal, slower cognitive task performance, introversion,
      agreeableness, and high reactive control; specific hyperactivity-impulsivity was
      associated with rule-breaking/aggressive behavior, social problems, errors during
      set-shifting, extraversion, disagreeableness, and low reactive control. It is
      concluded that the bifactor model provides better explanation of heterogeneity
      within ADHD than DSM-IV ADHD symptom counts or subtypes.

PMID- 21735051
TI  - Effects of child psychopathology on maternal depression: the mediating role of
      child-related acute and chronic stressors.
AB  - In light of recent research highlighting the potential effects of children's
      behavior on mothers' mental health, the current study examined 679 mothers and
      their adolescent children from a community-based sample to determine the effects
      of youth psychopathology on maternal depression and levels of child-related
      stress in mothers' lives. It was hypothesized that the number of past clinical
      diagnoses in 15-year-old adolescents would predict the presence of maternal
      depression at youth age 15 and 5 years later, as well as more episodes of
      maternal depression during the follow-up period. Furthermore, it was hypothesized
      that increased levels of child-related stress in mothers' lives would mediate
      these relationships. Regression analyses indicated that past youth diagnoses do
      confer risk for the presence of current and future maternal depression, as well
      as more episodes of maternal depression, and mediation analyses revealed that
      child-related acute and chronic stress were mediators of the relationship between
      youth diagnoses and the presence of maternal depression at follow-up. Findings
      suggest that increased levels of child-related objective stress in mothers' lives
      are one mechanism by which children's psychopathology affects mothers' future
      risk for depression.

PMID- 21735052
TI  - Solid food refusal as the presenting sign of vitamin B12 deficiency in a
      breastfed infant.
AB  - Dietary vitamin B(12) (vitB(12)) deficiency, although common in the elderly, is
      rare in childhood. We report on an exclusively breastfed 8-month-old infant,
      presenting with persistent refusal of solid foods. Three months later,
      developmental regression and failure to thrive led to the diagnosis of vitB(12)
      deficiency, as a consequence of a subclinical pernicious anaemia with vitB(12)
      deficiency in the mother. Treating the infant with parenteral vitB(12) induced
      prompt recovery including acceptance of weaning food. CONCLUSION: This case
      illustrates refusal of complementary foods as a presenting symptom of vitB(12)
      deficiency in a breastfed infant. Symptoms, diagnostic tests and treatment of
      vitamin B(12) deficiency are reviewed. Early diagnosis and treatment are
      important to prevent irreversible neurological damage.

PMID- 21735053
TI  - Desferrioxamine treatment of iron overload secondary to RH isoimmunization and
      intrauterine transfusion in a newborn infant.
AB  - Intrauterine transfusion is the standard of care in the management of severe Rh
      isoimmunization. Desferrioxamine has been used for the treatment of iron overload
      secondary to hemolysis and intrauterine transfusions in Rh isoimmunization cases.
      Here, we report a preterm infant born at 34 weeks of gestational age who had
      formerly received intrauterine transfusions for Rhesus hemolytic disease and
      presented with severe hyperferritinemia and elevated liver enzymes in the first
      week of life. Desferrioxamine treatment was started due to a ferritin level of
      28,800 ng/ml and continued for 13 weeks. Although the treatment was successful,
      we observed resistant leukopenia which resolved after the cessation of treatment.
      In conclusion, iron overload secondary to intrauterine transfusions can be
      treated successfully with desferrioxamine; however, neonatologists must be aware
      of the possible side effects of this drug which has been used in only a limited
      number of newborns.

PMID- 21735054
TI  - Prevalence of overweight and obesity in children aged 6-13 years-alarming
      increase in obesity in Cracow, Poland.
AB  - This study in children aged 6-13 years (n = 1,499) was performed between October
      2008 and March 2009. Height and weight measurements were taken to calculate BMI.
      The prevalence of overweight and obesity was determined by means of IOTF cut-offs
      with respect to age. Alarming is the fact that the percentage of obese children
      in Cracow increased dramatically from 1.04% in boys and 0.20% in girls in 1971 to
      7% in boys and 3.6% in girls in 2009. In this report, a higher percentage of
      overweight boys was observed in rural boys (28.14%) than in urban ones (27.31%).
      Obesity was identified in an almost twice as high percentage of urban boys
      (7.78%) as in rural ones (3.52%). A higher percentage of overweight girls was
      registered in rural areas (16.49%) than in urban ones (16.09%). Obesity was
      prevailing in rural girls (4.12%) relative to their urban counterparts (3.44%).
      The highest number of overweight urban boys was diagnosed in the group of 12-year
      olds (n = 48) and rural boys in the group of 10-year-olds (n = 39), as well as in
      urban girls aged 11 (n = 17) and rural girls aged 9 (n = 9). The highest number
      of obesity was observed in rural boys aged 12 (n = 3) and in urban boys aged 9
      and 10 (n = 9 in both groups). In the group of girls, obesity prevailed in urban
      9-year-olds (n = 5) and in rural 7-year-olds (n = 5). CONCLUSIONS: Overweight and
      obesity affect boys almost twice as frequently as girls. Obesity is twice as
      frequent in urban boys as in their rural peers.

PMID- 21735055
TI  - Spontaneous clearance of hepatitis C virus in vertically infected children.
AB  - Spontaneous viral clearance of hepatitis C virus (HCV) has been reported to occur
      in children with vertical HCV infection. However, factors which are associated
      with or predispose for clearance are largely unknown. In this case series we
      retrospectively analyzed laboratory parameters associated with spontaneous
      clearance of HCV in vertically infected children. The charts of six patients with
      documented spontaneous viral clearance by the age of 5 years were reviewed
      regarding clinical course, liver function tests (LFTs) and trend of HCV gene copy
      numbers. Spontaneous viral elimination was observed between the 25th and 52nd
      months of age. All patients had elevated LFTs, which peaked before 20 months of
      life. Peak LFT elevation was followed by normalization of LFTs and decline in
      viral load. These findings suggest that, in vertically HCV-infected children, a
      potent inflammatory response in the liver precedes viral clearance. Therefore,
      temporarily elevated LFTs, followed by a decline of viral load may be indicative
      of a near viral clearance in early childhood. CONCLUSION: Further investigations
      regarding the development of optimal treatment algorithms should take into
      account factors, which are associated with possible spontaneous viral resolution,
      such as viral genotype, favourable host factors as well as direct and indirect
      parameters of antiviral immunity, and the individual course of viral replication.

PMID- 21735056
TI  - Telomere length dynamics in the human pituitary gland: robust preservation
      throughout adult life to centenarian age.
AB  - Many studies have demonstrated the association between telomere length in mitotic
      cells and aging, but the relationship between telomere length in post-mitotic
      cells and aging in human populations has remained largely unclear. In this study,
      we assessed the dynamics of telomere length (terminal restriction fragment length
      TRF) in normal pituitary glands obtained at autopsy from 65 patients aged between
      0 and 100 years. The initial length (the value for neonatal pituitary) was 14.2
      +/- 1.1 kbp (mean of the median TRF value +/- SD), being the longest among those
      for other systemic organs. The annual telomere reduction rates for pituitary (21
      bp) were equivalent to or below the lowest values for various cells and tissues.
      Hence, comparison of TRF lengths among organs revealed that the pituitary gland
      retained longer telomeres than most other organs throughout life. The median TRF
      value showed a significant decrease between newborns and the 61-75 age group, but
      then leveled off or increased slightly in advanced age groups. These data
      indicate that innate telomere length is highly conserved in the pituitary and
      suggest that pituitary telomere length provides a good basic indicator for
      studies of telomere biology.

PMID- 21735057
TI  - Malignant lymphomas and autoimmunity-a single center experience from Hungary.
AB  - Autoimmune diseases and malignant lymphomas have numerous similarities in their
      etiology and pathogenesis. Patients with autoimmune disorders have increased risk
      to develop non-Hodgkin's lymphomas, yet little is known about the occurrence of
      autoimmune features within lymphoma patients. Our aim was to examine the
      prevalence of autoimmune diseases among patients with non-Hodgkin's (NHL) and
      Hodgkin's lymphoma (HL). We reviewed 352 patients' charts with malignant
      lymphomas to assess the rate of associated autoimmune diseases. Of 231 NHL
      patients, 30 (12.9%) had autoimmune disorders, while there were 11 patients who
      suffered from more than one disease entity. It was Sjogren's syndrome that
      occurred in the largest number (eight cases), other frequent entities were
      undifferentiated connective tissue disease (seven), thyroiditis (six), rheumatoid
      arthritis (four), and systemic vasculitis (four). The female/male ratio was
      significantly different between patients with or without autoimmune diseases,
      while no other clinical features differed significantly between the two groups.
      Ten patients (33.3%) were initially diagnosed with lymphoma, 13 (43.3%) of them
      had already been diagnosed with autoimmune disease at the time of lymphoma
      occurrence. Six patients (20%) with previously diagnosed immunological disorder
      developed new autoimmune condition after the treatment of lymphoma. Lymphoma and
      autoimmune disease occurred simultaneously in one patient. Among the 121 HL
      patients, 14 (11.5%) had associated autoimmune disease. Ten patients developed
      thyroiditis after the lymphoma treatment, two had immune thrombocytopenia, and
      one had autoimmune hemolytic anemia. One female patient was diagnosed with
      systemic sclerosis 10 years before the onset of HL. Our results highlight that an
      increased risk for the development of autoimmune diseases should be considered in
      patients both with NHL and HL.

PMID- 21735058
TI  - Resistin and visfatin: are they valuable enough to be the differential diagnosis
      in familial Mediterranean fever with acute appendicitis?
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease which
      predominantly affects certain ethnic groups mainly Sephardic Jews, Turks, Arabs,
      and Armenians. Differential diagnosis of an attack of FMF with appendicitis could
      be difficult in patients presenting with acute abdomen. Circulating levels of
      resistin and visfatin have been shown to increase in several inflammatory
      conditions. In this study we aimed to investigate the role of resistin and
      visfatin in diseases activity by monitoring these adipokines' levels in patients
      with FMF (attacks and attack-free period) and acute appendicitis. The study
      involves four groups: group 1-31 FMF patients at attack (M/F, 14/17), group 2-27
      FMF patients at attack-free period (M/F, 9/18), group 3-29 acute appendicitis
      patients (M/F, 16/13), and group 4-20 healthy controls (M/F, 10/10). Erythrocyte
      sedimentation rate, C-reactive protein, white blood cell count, fibrinogen,
      resistin, visfatin, interleukin-1beta, interleukin-6, interleukin-10, TNF-alpha,
      and IFN-gamma were evaluated concurrently. Resistin level could be a useful test
      in diagnosis of FMF patients in attacks period but not in acute appendicitis as
      differential diagnosis. Measuring visfatin levels would not give additional
      information neither for attacks and attack-free period nor FMF attack and
      appendicitis.

PMID- 21735059
TI  - GABAA receptors involved in sleep and anaesthesia: beta1- versus beta3-containing
      assemblies.
AB  - The histaminergic neurons of the posterior hypothalamus (tuberomamillary nucleus
      TMN) control wakefulness, and their silencing through activation of GABA(A)
      receptors (GABA(A)R) induces sleep and is thought to mediate sedation under
      propofol anaesthesia. We have previously shown that the beta1 subunit preferring
      fragrant dioxane derivatives (FDD) are highly potent modulators of GABA(A)R in
      TMN neurons. In recombinant receptors containing the beta3N265M subunit, FDD
      action is abolished and GABA potency is reduced. Using rat, wild-type and
      beta3N265M mice, FDD and propofol, we explored the relative contributions of
      beta1- and beta3-containing GABA(A)R to synaptic transmission from the GABAergic
      sleep-on ventrolateral preoptic area neurons to TMN. In beta3N265M mice, GABA
      potency remained unchanged in TMN neurons, but it was decreased in cultured
      posterior hypothalamic neurons with impaired modulation of GABA(A)R by propofol.
      Spontaneous and evoked GABAergic synaptic currents (IPSC) showed beta1-type
      pharmacology, with the same effects achieved by 3 MUM propofol and 10 MUM
      PI24513. Propofol and the FDD PI24513 suppressed neuronal firing in the majority
      of neurons at 5 and 100 MUM, and in all cells at 10 and 250 MUM, respectively.
      FDD given systemically in mice induced sedation but not anaesthesia. Propofol
      induced currents were abolished (1-6 MUM) or significantly reduced (12 MUM) in
      beta3N265M mice, whereas gating and modulation of GABA(A)R by PI24513 as well as
      modulation by propofol were unchanged. In conclusion, beta1-containing (FDD
      sensitive) GABA(A)R represent the major receptor pool in TMN neurons responding
      to GABA, while beta3-containing (FDD-insensitive) receptors are gated by low
      micromolar doses of propofol. Thus, sleep and anaesthesia depend on different
      GABA(A)R types.

PMID- 21735060
TI  - SGK1-dependent stimulation of intestinal SGLT1 activity by vitamin D.
AB  - The serum- and glucocorticoid-inducible kinase SGK1 has previously been shown to
      mediate the glucocorticoid-dependent stimulation of several intestinal transport
      systems including the electrogenic glucose transporter SGLT1. In squamous
      carcinoma cells, SGK1 expression is stimulated by 1,25(OH)2D3, the biologically
      active metabolite of vitamin D. The present study explored whether vitamin D
      influences the intestinal SGLT1 activity. Jejunal SGLT1 activity was determined
      by Ussing chamber experiments. Under a normal diet, the electrogenic glucose
      transport was similar in SGK1 knockout (sgk1 ( -/- )) and wild type mice (sgk1 (
      +/+ )). Following a vitamin D-rich diet (14 days 10,000 I.U. vitamin D), the SGK1
      transcript levels as well as the SGLT1 protein abundance were increased in
      sgk1(+/+) mice. Moreover, SGLT1 activity was increased in sgk1(+/+) mice but not
      in sgk1(-/-) mice following a vitamin D-rich diet. Furthermore, an oral glucose
      load was followed by an increase in the plasma glucose concentration to
      significantly higher values in sgk1(+/+) mice treated with a vitamin D-rich diet
      than in untreated sgk1(+/+) mice. In conclusion, vitamin D treatment upregulates
      the expression of SGK1, which in turn enhances SGLT1 activity.

PMID- 21735061
TI  - Marker peptide selection for the determination of hazelnut by LC-MS/MS and
      occurrence in other nuts.
AB  - The aim of this work was identifying and selecting hazelnut marker peptides and
      subsequently developing a complementary method of common immunoassay for the
      detection of hazelnut. For this purpose, at first, an in silico digestion of
      three major hazelnut allergens (Cor a 8, Cor a 9 and Cor a 11) was performed to
      get information about expected peptides. After extraction and trypsin digestion
      of hazelnut proteins, the samples were measured with tandem mass spectrometry
      (MS/MS) by direct infusion, which led to identification of 14 peptides. Eight of
      them with the highest MS signal were synthesized and used as standards for
      developing a liquid chromatography (LC)-MS/MS method in selected reaction
      monitoring (SRM) mode. Since almost all food allergens derived from nuts belong
      to the seed storage protein family and have homologue structure, a Basic Local
      Alignment Search Tool (BLAST) search was performed to identify the hazelnut
      specificity of the developed method. According to BLAST, only one peptide occurs
      in three other nuts, and the remaining seven selected peptides are hazelnut
      specific. Additionally to hazelnut, the eight other listed nuts in Directive
      2003/89/EC as allergen were extracted, digested and measured with the developed
      method to prove the BLAST results. The analytical data confirmed that six
      peptides are hazelnut specific, on the contrary to anti-hazelnut antibodies,
      which showed cross-reactivities to all other nut extracts. Comparing these
      results, it could be shown that with this LC-MS/MS method in SRM mode, the
      specific detection of hazelnut is possible.

PMID- 21735062
TI  - First chemical evidence of royal purple as a material used for funeral treatment
      discovered in a Gallo-Roman burial (Naintre, France, third century AD).
AB  - Violet-purple residues collected from a Gallo-Roman burial dated back to the
      second half of the third century A.D. and excavated at Naintre (France) were
      chemically investigated by multi-analytical methodology involving the use of
      Raman spectroscopy, direct exposure-mass spectrometry (DE-MS) and high
      performance liquid chromatography (HPLC-UV-visible). Little is known about
      funeral treatment and rituals during Roman times. Retrieving valuable information
      on these by chemical analysis of organic residues was thus a key aspect of this
      work. Analyses demonstrated the presence of the very precious purple colorant
      obtained from shellfish glands commonly known as Tyrian or royal purple and its
      exceptional preservation. Chemical investigation and archaeological evidence have
      shown that purple was widely spread after the deposition of the body for burial.
      These results are the earliest chemical evidence of purple colorant used during
      funeral rituals (not as textile dye) and enabled us to highlight new aspects of
      funeral practices in Roman times.

PMID- 21735063
TI  - A multi-analytical approach for the characterization of powders from the Pompeii
      archaeological site.
AB  - Nine black powders found in Pompeii houses in three different types of bronze
      vessels (cylindrical theca atramentaria, unguentaries, and aryballoi) were
      characterized in order to assess a correspondence between the composition and the
      type of vessel and, possibly, to verify if these powders were inks or not. For
      the compositional characterization, a multi-analytical approach was adopted,
      which involved the use of scanning electron microscopy-energy dispersive X-ray,
      Fourier-transformed infrared spectroscopy, Raman, X-ray diffraction, electron
      paramagnetic resonance spectroscopy, thermogravimetric analysis, gas
      chromatography coupled with mass spectrometry (GC/MS), and pyrolysis GC/MS.
      Powders contained in cylindrical theca atramentaria form a homogeneous group, and
      their organic and inorganic compositions suggest that they were writing inks,
      while powders contained in unguentaries and aryballoi could have had several
      different uses, including writing inks and cosmetics. Furthermore, the
      composition profile of the powders found in cylindrical cases shows that, at 79
      AD: , in Pompeii, carbon-based inks were still used for writing, and iron gall
      inks had not been introduced yet.

PMID- 21735064
TI  - Highlights of the 59th Conference on Mass Spectrometry and Allied Topics of the
      ASMS in Denver, Colorado.

PMID- 21735065
TI  - Secretome of the preimplantation human embryo by bottom-up label-free proteomics.
AB  - A bottom-up label-free mass spectrometric proteomic strategy was used to analyse
      the protein profiles of the human embryonic secretome. Culture media samples used
      for embryonic culture of patients undergoing intracytoplasmic sperm injection
      cycles were selected as a test case for this exploratory proof-of-principle
      study. The media were stored after embryo transfer and then pooled into positive
      (n = 8) and negative (n = 8) implantation groups. The absolute quantitative
      bottom-up technique employed a multidimensional protein identification technology
      based on separation by nano-ultra-high pressure chromatography and identification
      via tandem nano-electrospray ionization mass spectrometry with data-independent
      scanning in a hydrid QqTOF mass spectrometer. By applying quantitative bottom-up
      proteomics, unique proteins were found exclusively in both the positive- and
      negative-implantation groups, which suggest that competent embryos express and
      secrete unique biomarker proteins into the surrounding culture medium. The
      selective monitoring of these possible secretome biomarkers could make viable
      procedures using single-embryo transfer.

PMID- 21735066
TI  - Highly specific capture and direct MALDI-MS analysis of phosphorylated peptides
      using novel multifunctional chitosan-GMA-IDA-Fe (III) nanosphere.
AB  - In this study, we describe a method for highly specific enrichment of
      phosphopeptides with multifunctional chitosan-glycidyl methacrylate (GMA)
      iminodiacetic acid (IDA)-Fe (III) nanospheres for direct analysis by matrix
      assisted laser desorption-ionization mass spectrometry (MALDI-MS). This is the
      first time that chitosan has been used to create nanospheres support material for
      selective enrichment of phosphopeptides by modification with GMA, derivatization
      with IDA, and loading with Fe (III) ions. Chitosan-GMA-IDA-Fe (III) nanospheres
      with a diameter of 20 to 100 nm have multifunctional chemical moieties which
      confer unique properties, good dispersibility in highly acidic binding buffers,
      as well as good biocompatibility and chemical stability which improves their
      specific interaction with phosphopeptides using various types of acid binding
      buffers. The process of enrichment is very simple, quick, efficient, and
      specific. Its high specificity and efficiency for purification of phosphopeptides
      is reflected in the very low and substoichiometric amounts of phosphopeptides
      which can be detected, in quantities as low as 1:3,000 M ratios. Compared with
      other state-of the-art technologies such as the use of conventional Fe(3+)-IMAC
      and TiO(2), these chitosan nanosphere techniques show superior specificity and
      sensitivity. Moreover, the resultant chitosan-GMA-IDA-Fe(3+) nanosphere-absorbed
      phosphopeptides can be either directly analyzed by MALDI-TOF MS analysis or
      eluted and further analyzed by nano-LC-MS/MS.

PMID- 21735067
TI  - Determination of the concentration of nitrogenous bio-organic compounds using an
      isotope ratio mass spectrometer operating in continuous flow mode.
AB  - The quality of the determination of compound-specific isotopic content at natural
      abundance by gas chromatography-isotope ratio measurement-mass spectrometry (GC
      irm-MS) relies on the stability of the voltage generated by the ion detector
      Faraday cages. The application of GC-irm-MS to the determination of delta(13)C
      (0/00) and delta(15)N (0/00) is now routine. However, for numerous applications,
      it is necessary to determine both the isotope content (delta(15)N) and the
      quantity (in micromoles) of analyte present. We now show that it is possible for
      nitrogen-containing compounds to measure how much analyte is present with an irm
      mass spectrometer linked to a GC by exploiting the integrated N(2) total ion
      current intensity (Vs) generated by measuring the (15)N/(14)N isotope ratio. The
      method is validated over a range of concentration (2-70 mmol/L) and delta(15)N (
      70 to +500/00) values for six molecules of diverse chemical nature and
      functionality (nortropine, norpseudotropine, nortropinone, cysteine, taurine,
      glutathione). It is shown that once the ion current is calibrated, the
      quantitative values are of a comparable quality to those obtained from GC with
      flame ionization detection (GC-FID). In addition, it is demonstrated that over a
      definable range, the delta(15)N (0/00) value is independent of the quantity of
      analyte introduced, confirming the validity of this method.

PMID- 21735068
TI  - Diagnostic performance of 320-slice multidetector computed tomography coronary
      angiography in patients after coronary artery bypass grafting.
AB  - OBJECTIVES: To evaluate the diagnostic performance of 320-slice computed
      tomography coronary angiography (CTA) in the evaluation of patients with prior
      coronary artery bypass grafting (CABG). Invasive coronary angiography (ICA)
      served as the standard of reference, using a quantitative approach. METHODS: CTA
      studies were performed using CT equipment with 320 detector-rows, each 0.5 mm
      wide, and a gantry rotation time of 0.35 s. All grafts, recipient and nongrafted
      vessels were deemed interpretable or uninterpretable. The presence of significant
      (>=50%) stenosis and occlusion were determined on vessel and patient basis.
      Results were compared to ICA using quantitative coronary angiography. RESULTS: A
      total of 40 patients (28 men, 76 +/- 15 years), with 89 grafts, were included in
      the study. On a graft analysis, the sensitivity, specificity, positive and
      negative predictive values in the evaluation of significant stenosis were 96%,
      92%, 83% and 98% respectively. The diagnostic accuracy for the assessment of
      recipient and nongrafted vessels was 89% and 80%, respectively. The diagnostic
      accuracy for the assessment of graft, recipient and nongrafted vessel occlusion
      was 96%, 92% and 100%, respectively. CONCLUSIONS: 320-slice CTA allows accurate
      non-invasive assessment of significant graft, recipient vessel and nongrafted
      vessel stenosis in patients with prior CABG.

PMID- 21735069
TI  - Cell tracking in cardiac repair: what to image and how to image.
AB  - Stem cell therapies hold the great promise and interest for cardiac regeneration
      among scientists, clinicians and patients. However, advancement and distillation
      of a standard treatment regimen are not yet finalised. Into this breach step
      recent developments in the imaging biosciences. Thus far, these technical and
      protocol refinements have played a critical role not only in the evaluation of
      the recovery of cardiac function but also in providing important insights into
      the mechanism of action of stem cells. Molecular imaging, in its many forms, has
      rapidly become a necessary tool for the validation and optimisation of stem cell
      engrafting strategies in preclinical studies. These include a suite of
      radionuclide, magnetic resonance and optical imaging strategies to evaluate non
      invasively the fate of transplanted cells. In this review, we highlight the state
      of-the-art of the various imaging techniques for cardiac stem cell presenting the
      strengths and limitations of each approach, with a particular focus on clinical
      applicability.

PMID- 21735070
TI  - Cannabinoids inhibit migration of microglial-like cells to the HIV protein Tat.
AB  - Microglia are a population of macrophage-like cells in the central nervous system
      (CNS) which, upon infection by the human immunodeficiency virus (HIV), secrete a
      plethora of inflammatory factors, including the virus-specified trans-activating
      protein Tat. Tat has been implicated in HIV neuropathogenesis since it elicits
      chemokines, cytokines, and a chemotactic response from microglia. It also harbors
      a beta-chemokine receptor binding motif, articulating a mode by which it acts as
      a migration stimulus. Since select cannabinoids have anti-inflammatory
      properties, cross the blood-brain barrier, and target specific receptors, they
      have potential to serve as agents for dampening untoward neuroimmune responses.
      The aim of this study was to investigate the effect of select cannabinoids on the
      migration of microglial-like cells toward Tat. Using a mouse BV-2 microglial-like
      cell model, it was demonstrated that the exogenous cannabinoids Delta-9
      tetrahydrocannabinol (THC) and CP55940 exerted a concentration-related reduction
      in the migration of BV-2 cells towards Tat. A similar inhibitory response was
      obtained when the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) was used.
      The CB(2) receptor (CB2R) antagonist SR144528, but not the CB(1) receptor (CB1R)
      antagonist SR141716A, blocked this inhibition of migration. Similarly, CB2R
      knockdown with small interfering RNA reversed the cannabinoid-mediated
      inhibition. In addition, the level of the beta-chemokine receptor CCR-3 was
      reduced and its intracellular compartmentation was altered. These results
      indicate that cannabinoid-mediated inhibition of BV-2 microglial-like cell
      migration to Tat is linked functionally to the CB2R. Furthermore, the results
      indicate that activation of the CB2R leads to altered expression and
      compartmentation of the beta-chemokine receptor CCR-3.

PMID- 21735071
TI  - Components of behavioural impulsivity and automatic cue approach predict unique
      variance in hazardous drinking.
AB  - RATIONALE: Hazardous drinking is associated with both increased impulsivity and
      automatic approach tendencies elicited by alcohol-related cues. However,
      impulsivity is a multi-factorial construct, and it is currently unclear if all
      components of impulsivity are associated with heavy drinking. Furthermore,
      emerging evidence suggests that the relationships between hazardous drinking and
      automatic alcohol cognitions may be moderated by individual differences in
      impulsivity. OBJECTIVES: The aim of this study was to investigate the
      independence of measures of impulsivity and their association with hazardous
      drinking, and to examine if the relationship between hazardous drinking and
      automatic alcohol approach tendencies would be moderated by individual
      differences in impulsivity. METHODS: Ninety-seven social drinkers (65 female)
      completed questionnaire measures of trait impulsivity, alcohol consumption and
      hazardous drinking. Participants also completed computerised measures of
      automatic alcohol approach tendencies (stimulus-response compatibility (SRC)
      task), and two behavioural measures of impulsivity (Go/No-go and delay
      discounting tasks). RESULTS: Principal component analysis revealed that the two
      measures of behavioural impulsivity were distinct from each other and from self
      reported trait impulsivity, although self-reported non-planning impulsivity
      loaded on to two factors (trait impulsivity and delay discounting). Furthermore,
      all measures of impulsivity predicted unique variance in hazardous drinking as
      did automatic alcohol approach tendencies, although the latter relationship was
      not moderated by impulsivity. CONCLUSIONS: These results indicate that multiple
      components of impulsivity and automatic alcohol approach tendencies explain
      unique variance in hazardous drinking.

PMID- 21735072
TI  - Long-term (3-year) effectiveness of haloperidol, risperidone and olanzapine:
      results of a randomized, flexible-dose, open-label comparison in first-episode
      nonaffective psychosis.
AB  - RATIONALE: To enhance the effectiveness of antipsychotics in first-episode
      psychosis is crucial in order to achieve the most favourable prognosis.
      Difference in effectiveness between antipsychotics is still under debate.
      OBJECTIVE: The purpose of this study is to determine the long-term (3-year)
      effectiveness and efficacy of haloperidol, risperidone and olanzapine in first
      episode schizophrenia-spectrum disorders. METHOD: This is a prospective,
      randomized, open-label study. Data for the present investigation were obtained
      from a large epidemiologic and 3-year longitudinal intervention programme of
      first-episode psychosis. One hundred seventy-four patients were randomly assigned
      to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and
      followed up for 3 years. The primary effectiveness measure was all-cause of
      treatment discontinuation. In addition, an analysis based on per-protocol
      populations was conducted in the analysis for clinical efficacy. RESULTS: The
      treatment discontinuation rate for any cause differed significantly between
      treatment groups (chi (2) = 10.752; p = 0.005), with a higher rate in haloperidol
      than in risperidone and olanzapine. The difference in the discontinuation rate
      between risperidone and olanzapine showed a tendency towards significance (chi
      (2) = 3.022; p = 0.082). There was a significant difference in the mean time to
      all-cause discontinuation between groups (log-rank chi ( 2 ) = 12.657;df = 2; p =
      0.002). There were no significant advantages to any of the three treatments in
      reducing the psychopathology severity. CONCLUSIONS: After 3 years of treatment, a
      lower effectiveness was observed in haloperidol compared to second-generation
      antipsychotics (SGAs). The use of SGAs for the treatment of early phases of
      nonaffective psychosis may enhance the effectiveness of antipsychotics.

PMID- 21735073
TI  - Effect of thought suppression on desire to smoke and tobacco withdrawal symptoms.
AB  - RATIONALE: Suppressing smoking thoughts has been shown to result in elevated
      smoking. However, the effect of suppressing smoking thoughts on desire to smoke
      and withdrawal symptoms has not been investigated. OBJECTIVES: We examined the
      effects of suppressing smoking thoughts on the subsequent desire to smoke and on
      tobacco withdrawal symptoms, relative to groups that were either thinking about
      anything they wished or actively thinking about smoking. METHODS: A randomised
      experimental study compared the effects of three manipulations (suppressed
      smoking thoughts, expressed smoking thoughts and thoughts of anything they
      wished) on desire and withdrawal immediately after the manipulation and 5 and 10
      min after. RESULTS: Suppressing smoking thoughts did not result in elevated
      subsequent desire to smoke, relative to the other manipulations. Suppressing
      smoking thoughts resulted in a significant elevation in hunger ratings, relative
      to the other manipulations, at all measurement times. There were no significant
      effects for the other withdrawal symptoms. Self-reported greater use of thought
      suppression in everyday life was significantly associated with greater desire to
      smoke at baseline and was associated with lower mindfulness scores. CONCLUSIONS:
      Laboratory-instructed suppression of smoking thoughts is associated with
      increased reports of hunger but did not lead to increases in other withdrawal
      symptoms or elevated desire to smoke. Reports of everyday use of thought
      suppression are associated with elevated desire to smoke at baseline. Further
      investigations need to assess the effect of suppressing smoking cravings, instead
      of general smoking thoughts, on desire to smoke and tobacco withdrawal.

PMID- 21735074
TI  - Enhancement of the hypothalamic-pituitary-adrenal axis but not cytokine responses
      to stress challenges imposed during withdrawal from acute alcohol exposure in
      Sprague-Dawley rats.
AB  - RATIONALE: Alcohol withdrawal is associated with reduced activity, increased
      anxiety, and other signs of distress. OBJECTIVE: The goal of the current studies
      was to determine whether acute ethanol exposure would alter hypothalamic
      pituitary-adrenal (HPA) axis reactivity and cytokine responses to stress
      challenges imposed during the withdrawal period. METHODS: Male Sprague-Dawley
      rats were intubated with 4 g/kg of ethanol to simulate acute binge-like ethanol
      intake. After characterizing the blood ethanol concentrations (BECs; Experiment
      1), exploratory activity in a novel environment was explored at 10, 14 and 18 h
      after ethanol (Experiment 2) to characterize altered activity patterns indicative
      of withdrawal. In Experiment 3, rats were exposed to footshock during withdrawal
      to examine whether prior ethanol exposure would alter cytokine and HPA axis
      responses to stress. Experiments 4 and 5 investigated HPA axis sensitivity and
      gene expression changes during restraint imposed during withdrawal. RESULTS:
      Prior ethanol exposure produced a period of stress hyper-reactivity evidenced by
      an enhanced HPA axis response (increased corticosterone and adrenocorticotropic
      hormone) observed during withdrawal. While this hyper-reactivity in response to
      two different stress challenges (novel environment and restraint) was accompanied
      by profound behavioral changes indicative of withdrawal, no alterations in
      cytokine changes evoked by stress were observed. CONCLUSIONS: Taken together,
      these findings provide support for the hypothesis that alcohol withdrawal
      enhances HPA axis reactivity to stress challenges, though not likely as the
      result of heightened inflammatory signaling, and may have implications for
      understanding the mechanisms by which stress impacts relapse drinking in humans.

PMID- 21735075
TI  - Xanthoceraside attenuates amyloid beta peptide25-35-induced learning and memory
      impairments in mice.
AB  - RATIONALE: In Alzheimer's disease (AD), the deposition of amyloid peptides is
      invariably associated with oxidative stress and inflammatory responses.
      Xanthoceraside has anti-inflammatory and antioxidative activities. However, it
      remains unclear whether xanthoceraside improves amyloid beta (Abeta)-induced
      neurotoxicity. OBJECTIVES: The purpose of this study was to examine the effect of
      xanthoceraside on behavioral impairments, inflammatory responses, and oxidative
      stress induced by Abeta peptide(25-35) (Abeta(25-35)) in mice. MATERIALS AND
      METHODS: The mice were treated orally with xanthoceraside (0.02, 0.08, or 0.32
      mg/kg, once daily) after the intracerebroventricular injection of Abeta(25-35)
      (day 0). Cognitive functions were evaluated in Y-maze (day 6) and novel object
      recognition tests (days 7 and 8). Inducible nitric oxide synthase (iNOS) and
      nitrotyrosine levels in the hippocampus were examined (day 9). The mRNA
      expressions of iNOS and interleukin-4 (IL-4) in the hippocampus were measured 2 h
      and 3 days after the Abeta(25-35) injection by real-time reverse transcription
      polymerase chain reaction. RESULTS: Xanthoceraside significantly attenuated
      behavioral impairments induced by Abeta(25-35) in the Y-maze and novel object
      recognition tests. Repeated treatment with xanthoceraside significantly inhibited
      the increase in the expression of iNOS and nitrotyrosine in the hippocampus
      induced by Abeta(25-35), which is associated with an enhanced expression of the
      IL-4 mRNA. CONCLUSIONS: These findings suggest that xanthoceraside attenuates
      memory impairments through amelioration of oxidative stress and inflammatory
      responses induced by Abeta(25-35) and is a potential candidate for an AD
      treatment.

PMID- 21735076
TI  - Fructose increases the resistance of Rhodobacter capsulatus to the toxic oxyanion
      tellurite through repression of acetate permease (ActP).
AB  - The highly toxic oxyanion tellurite (TeO(3) (2-)) enters the cells of the
      facultative photosynthetic bacterium Rhodobacter capsulatus through an acetate
      permease. Here we show that actP gene expression is down-regulated by fructose
      and this in turn determines a strong decrease of tellurite uptake and a parallel
      increase in the cells resistance to the toxic metalloid (from a minimal
      inhibitory concentration of 8 MUM up to 400 MUM tellurite under aerobic growth
      conditions). This demonstrates that there exists a direct connection between the
      level of tellurite uptake and the sensitivity of the cells to the oxyanion.

PMID- 21735077
TI  - Anxiety disorders in children and adolescents with autistic spectrum disorders: a
      meta-analysis.
AB  - There is considerable evidence that children and adolescents with autistic
      spectrum disorders (ASD) are at increased risk of anxiety and anxiety disorders.
      However, it is less clear which of the specific DSM-IV anxiety disorders occur
      most in this population. The present study used meta-analytic techniques to help
      clarify this issue. A systematic review of the literature identified 31 studies
      involving 2,121 young people (aged <18 years) with ASD, and where the presence of
      anxiety disorder was assessed using standardized questionnaires or diagnostic
      interviews. Across studies, 39.6% of young people with ASD had at least one
      comorbid DSM-IV anxiety disorder, the most frequent being specific phobia (29.8%)
      followed by OCD (17.4%) and social anxiety disorder (16.6%). Associations were
      found between the specific anxiety disorders and ASD subtype, age, IQ, and
      assessment method (questionnaire versus interview). Implications for the
      identification and treatment of anxiety in young people with ASD are discussed.

PMID- 21735078
TI  - Continuous glucose monitoring in gastroparesis.
AB  - BACKGROUND: Delayed gastric emptying can alter glucose levels in diabetic
      patients; hyperglycemia can delay gastric emptying. Continuous glucose monitoring
      (CGM) may be useful to assess the relationship between gastric emptying and blood
      glucose levels. AIMS: The aims of this study were to compare the postprandial
      blood glucose profile of patients with type 2 diabetes mellitus (T2DM) with and
      without gastroparesis, normal subjects, and patients with idiopathic
      gastroparesis (IG), and also to determine the effect of different meal
      compositions on glucose regulation in T2DM and normals. METHODS: Seven patients
      with IG, seven T2DM with gastroparesis, ten non-gastroparetic T2DM, and ten
      normal subjects underwent CGM during a low fat (Eggbeaters) meal. Glucose
      profiles were also studied in T2DM and normal subjects after high fat, high
      fiber, spicy, and Ensure liquid nutrient meals. RESULTS: After the Eggbeaters
      meal, the glucose profile of IGs and normals were similar. Diabetic patients with
      gastroparesis had similar peak postprandial blood glucose to nongastroparetic
      diabetics (231 +/- 26 vs. 232 +/- 18 mg/dl), but had a higher postprandial blood
      glucose at the end of the 4 h study (187 +/- 26 mg/dl vs. 97 +/- 10; P = 0.01).
      In contrast to normals, non-gastroparetic diabetics had higher mean postprandial
      blood sugar after the Eggbeaters meal (173 +/- 5 mg/dl) compared to high fat (157
      +/- 3; P = 0.002), spicy (133 +/- 2; P < 0.001) and Ensure meals (152 +/- 1; P <
      0.001). CONCLUSIONS: Blood glucose monitoring provides insight to the presence of
      gastroparesis in diabetic patients: diabetic gastroparetics had prolonged
      postprandial hyperglycemic profile as compared to non-gastroparetic diabetics. Of
      the meals tested, the low fat (Eggbeaters) meal was associated with the highest
      mean postprandial glucose in diabetics.

PMID- 21735079
TI  - Severe acute pancreatitis during pregnancy: eleven years experience from a
      surgical intensive care unit.
AB  - OBJECTIVE: Acute pancreatitis during pregnancy is a rare and dangerous disease.
      This study attempts to present a comprehensive analysis of severe acute
      pancreatitis (SAP) during pregnancy and to identify the factors associated with
      poor outcomes. METHODS: This study was a retrospective review of the medical
      records of SAP patients during pregnancy consecutively admitted into the Research
      Institute of General Surgery from 1999 to 2010. RESULTS: Information was
      collected on presentation, management, and outcome. Eighteen patients were
      identified to have been diagnosed with SAP during pregnancy. Eleven patients
      (61.1%) were nulliparous; most attacks (88.9%) occurred during the third
      trimester. There were seven cases with preterm labor, six with fetal losses, and
      no maternal death. The etiology was biliary disease in seven patients (38.9%),
      hypertriglyceridemia in five patients (27.8%), both biliary and
      hypertriglyceridemia in four patients (22.2%), and idiopathic in two patients
      (11.1%). Patients with failure in more than one (>=2) organ were more likely to
      result in fetal loss (OR = 25, P = 0.016). CONCLUSIONS: SAP during pregnancy is
      predominantly biliary in etiology, but a significant proportion is caused by
      hypertriglyceridemia. Patients with failure in at least two organs result in
      relatively worse fetal outcomes.

PMID- 21735080
TI  - Chylous ascites after laparoscopic Nissen fundoplication.

PMID- 21735081
TI  - Nonalcoholic fatty liver disease markers are associated with insulin resistance
      in type 1 diabetes.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been associated with the
      insulin resistance. AIMS: To explore the relationship between markers of NAFLD,
      namely concentrations of aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase (ALK), gamma-glutamyltransferase
      (GGT), ferritin and bilirubin and insulin resistance in type 1 diabetes. METHODS:
      Our study included 353 patients with type 1 diabetes. Insulin sensitivity was
      measured with estimated glucose disposal rate calculated using the equation: eGDR
      = 24.31 - (12.22 * WHR) - (3.29 * HT) - (0.57 * HbA1c); WHR = waist to hip ratio,
      HT = hypertension. Correlations and multiple logistic regressions analysis were
      performed to identify the relationships between NAFLD associated markers and
      eGDR, individual components of insulin resistance and risk of insulin resistance.
      RESULTS: AST, ALT, AST-to-ALT ratio, ALK and ferritin significantly correlated
      with insulin resistance measured by eGDR (r = -0.13, -0.14, 0.13, -0.18, and 
      0.24, respectively; all P < 0.05), and with individual components of insulin
      resistance, most notably WHR. In a multiple logistic regression model adjusted
      according to age, sex, duration of diabetes and BMI, increased levels of AST, ALT
      and ALK resulted in an increased risk for the development of insulin resistance
      in our subjects (OR = 1.03, 1.02, and 1.01, respectively; all P < 0.05).
      CONCLUSIONS: These findings indicate that higher levels of ALT, AST and ALK are
      additional markers of insulin resistance in type 1 diabetes and suggest that
      those subjects must be considered as potentially affected not only by a hepatic
      but also by a multisystemic disease through altered insulin sensitivity.

PMID- 21735082
TI  - Is intercellular space different among layers in normal esophageal mucosa? An
      electron microscopic study.
AB  - BACKGROUND/INTRODUCTION: Dilatation of intercellular space (IS) of esophageal
      epithelial cells is described as a sensitive early marker for epithelial damage
      by refluxate. Esophageal epithelia are morphologically subdivided into three
      layers according to the shape of the cells and nuclei. Meanwhile, ten
      transmission electron microscopy (TEM) photographs and ten randomly selected
      measurements per photo from gastroesophageal reflux disease (GERD) patients have
      been widely accepted without any theoretical criticism. We assumed that the IS
      differs among each layer and thus studied IS according to subdivided layers of
      normal esophageal epithelium. We also evaluated an optimal number of IS
      measurements per photograph. MATERIALS AND METHODS: Esophagogastroduodenoscopy
      was performed in 15 healthy adults without any symptom of GERD, taking biopsies
      from mucosa above 5 cm from the squamo-columnar junction. Tissues were handled
      and prepared for TEM, verifying three layers of esophageal mucosa, i.e., squamous
      cell layer, prickle cell layer, and basal layer. Ten digital photomicrographs
      were taken from each three layers by TEM, and ISs were measured with a
      computerized image analysis program. For the method of measuring IS, 5, 10, 20,
      30, and 40 measurements per photomicrograph were respectively performed by four
      different examiners. Mean value and intraclass correlation coefficient (ICC) was
      also yielded. RESULTS: Mean IS of lower esophagus irrelevant to three epithelial
      layers were 0.39 +/- 0.30 MUm. When subdivided into three layers, however, mean
      IS of squamous cell layer was 0.62 +/- 0.23 MUm, prickle cell layer 0.23 +/- 0.19
      MUm, and basal layer 0.55 +/- 0.36 MUm, with their difference statistically
      significant (p < 0.05). On the other hand, ICC of 5, 10, 20, 30, and 40
      measurements were 0.688, 0.917, 0.837, 0.790, and 0.765, respectively.
      CONCLUSIONS: Mean IS values of each three layers of esophageal epithelium in
      normal subjects were significantly different, and reconsideration of the standard
      measurement method is needed. Ten measurements per photo had an adequate inter
      observer agreement.

PMID- 21735083
TI  - Curry induces acid reflux and symptoms in gastroesophageal reflux disease.
AB  - BACKGROUND: There are limited data on the effect of curry on gastroesophageal
      reflux disease (GERD). Our objective was to study the effects of curry on GERD.
      METHODS: Symptomatic non-erosive gastroesophageal reflux disease (NERD) patients
      and healthy volunteers underwent ambulatory 24-h esophageal pH monitoring before
      consumption of either 400 or 800 ml of curry; they were monitored for 3 h
      thereafter for changes in esophageal pH and upper abdominal symptoms. Selected
      volunteers were monitored similarly after water ingestion. RESULTS: In total, 25
      NERD patients (23 males; mean age, 45 years) and 19 volunteers (13 males; mean
      age, 22 years) participated. In both patients and volunteers, curry ingestion
      induced more esophageal acid exposure than did ingestion of a similar volume of
      water. Curry induced significantly more esophageal acid exposure in NERD patients
      than in volunteers. Upper abdominal symptoms and esophageal acid exposure were
      more severe and persisted longer in patients than in volunteers. CONCLUSION:
      Curry induced more acid reflux and caused worse symptoms in patients with NERD
      than in healthy individuals. Patients with NERD should be advised to avoid curry
      ingestion.

PMID- 21735084
TI  - Continuous peritoneal drainage of large-volume ascites.
AB  - BACKGROUND: With the increasing population of individuals with cirrhosis, many of
      whom are not liver transplant candidates, large volume paracentesis as a medical
      therapy for ascites resistant to diuretic therapy has become increasingly
      utilized. AIM: To determine the safety and efficacy of continuous peritoneal
      drainage of large-volume ascites in Child Class-C cirrhosis. Subjects with no
      current clinical or laboratory findings of spontaneous bacterial ascites were
      studied. Each had a complete medical evaluation to document the etiology and
      severity of their liver disease as well as the identification of any confounding
      medical illness. A triple-phase abdominal CT of the abdomen was obtained in each
      individual to rule out any hepatoma. Upon completion of the above, a
      pericardiocentesis catheter was placed in the abdomen using the Seldinger
      technique and the ascites was drained continuously (to gravity) until no
      additional ascitic fluid could be removed or the total time of drainage was 72 h.
      The patient's weight, volume of ascitic fluid removed, ascitic fluid cell counts,
      ascitic fluid cultures, complete blood count and comprehensive metabolic profile
      were obtained immediately before and after the peritoneal catheter was removed.
      RESULTS: HCV cirrhosis accounted for 12 cases and alcoholic liver disease
      accounted for 8 cases (half the total of 40 cases), with 6 other diseases
      accounting for the remaining half. The ascitic fluid was drained continuously for
      2.5 +/- 0.08 days, with a removal of 13.3 +/- 0.5 l of ascitic fluid. No
      clinically significant change in the serum creatinine or ascitic fluid cells
      count occurred as a result of the procedure. The adverse effects of the procedure
      were minimal. 63% of the patients experienced some mild discomfort at the
      catheter insertion site, or local abdominal pain just prior to the removal of the
      catheter. Two patients developed a small abdominal wall hematoma that required no
      therapy. No patients experienced peritoneal hemorrhage, infection or renal
      dysfunction. CONCLUSION: (1) Continuous large-volume peritoneal drainage by
      gravity is safe and effective; (2) if the procedure is limited 72 h, no cases of
      ascitic fluid contamination/infection occur; and (3) it reduces the time between
      subsequent paracentesis based upon historical data.

PMID- 21735085
TI  - CT-enterography may identify small bowel tumors not detected by capsule
      endoscopy: eight years experience at Mayo Clinic Rochester.
AB  - BACKGROUND: Capsule endoscopy (CE) is widely accepted as the preferred diagnostic
      test in the evaluation of small bowel diseases. However, small bowel tumors (SBT)
      are sometimes missed by CE. Preliminary studies suggest that CT-enterography
      (CTE) may play a role in detecting SBT. AIMS: The purpose of this study was to
      compare the performance of CE and CTE in detecting SBT METHODS: This was a single
      center, retrospective study. Patients treated at the Mayo Clinic Rochester
      between January 2000 and December 2008 with a discharge diagnosis of SBT and
      negative initial esophagogastroduodenoscopy (EGD) and colonoscopy were identified
      through a search of the electronic medical records. Among 103 identified
      patients, 41 had undergone CE, CTE or both, and comprised our study group. The
      exact binomial sensitivity of CE and CTE in detecting SBT was calculated.
      Demographic characteristics, clinical presentation, results of diagnostic tests,
      and tumor characteristics were recorded for each patient. RESULTS: CTE and CE
      detected 38/41 (sensitivity 92.7%; 95% CI 80.1-98.5) and 8/27 (sensitivity 29.6%;
      95% CI 13.8-50.2) of the SBT identified at Mayo Clinic Rochester, respectively.
      Seventeen patients had both CTE and CE. In this subgroup of patients, CTE
      detected SBT in 16/17 (sensitivity 94.1; 95% CI 72.7-99.9) and CE in 6/17
      (sensitivity 35.3%; 95% CI 13.3-59). The matched paired difference in the
      sensitivity of two techniques in detecting SBT was statistically significant (P =
      0.004). CONCLUSION: CTE may identify SBT not diagnosed by CE.

PMID- 21735086
TI  - Inappropriate angiogenic response as a novel mechanism of duodenal ulceration and
      impaired healing.
AB  - BACKGROUND: Despite recent advances and better understanding of the etiology and
      the pathogenesis of gastrointestinal ulcer diseases, e.g., duodenal ulcer, the
      molecular events leading to ulcer development, delayed healing, and recurrence
      remain poorly elucidated. AIMS: After we found that duodenal ulcers did not heal
      despite increased levels of vascular endothelial growth factor (VEGF), we tested
      the hypothesis that an imbalance in angiogenic VEGF and anti-angiogenic
      endostatin and angiostatin might be important in the development and delayed
      healing of experimental duodenal ulcers. METHODS: Levels of VEGF, endostatin, and
      angiostatin, and the expression and activity of related matrix metalloproteinases
      (MMP) 2 and 9 were measured in scrapings of rat proximal duodenal mucosa in the
      early and late stages of chemically induced duodenal ulceration. Furthermore,
      animals were treated with recombinant endostatin and MMP 2 inhibitor to test the
      relationship between MMP2 and endostatin and their involvement in healing of
      experimental duodenal ulcers. RESULTS: A concurrent increase of duodenal VEGF,
      endostatin, and angiostatin was noted during duodenal ulceration. Endostatin
      treatment aggravated duodenal ulcer. Levels of MMP2, but not MMP9, were
      increased. Inhibition of MMP2 reduced levels of endostatin and angiostatin, and
      attenuated duodenal ulcers. CONCLUSIONS: Increased levels of endostatin and
      angiostatin induced by MMP2 delayed healing of duodenal ulcers despite
      concurrently increased VEGF. Thus, an inappropriate angiogenic response or
      "angiogenic imbalance" may be an important new mechanism in ulcer development and
      impaired healing.

PMID- 21735087
TI  - Endoscopic ultrasound in patients over 80 years old.
AB  - BACKGROUND: The data on the safety and utility of EUS in patients over 80 years
      of age is limited. OBJECTIVE: We investigated the indications, feasibility,
      safety, and clinical utility of EUS in the management of GI, pancreatobiliary,
      and mediastinal diseases. DESIGN: Retrospective study. SETTING: A tertiary
      referral university hospital. PATIENTS: Consecutive patients >=80 years of age
      referred over a 9-year period for EUS evaluation. RESULTS: A total of 265 EUS
      scans were performed in 232 patients with a mean age of 83.8 years. The
      indications for pancreatobiliary EUS were to evaluate a pancreatic mass (n = 60),
      pancreatic cyst (n = 18), pancreatitis (n = 10), dilated CBD in the setting of
      jaundice and/or biliary stricture (n = 20), dilated CBD with no jaundice and/or
      biliary stricture (n = 20). The indications for luminal gastrointestinal EUS were
      esophageal lesions (n = 21), gastric lesions (n = 30), duodenal lesions (n = 14),
      rectal lesions (n = 22), and gastrointestinal subepithelial lesions (n = 28). The
      indications for mediastinal EUS were mass/lymphadenopathy (n = 14). EUS-guided
      FNA (EUS-FNA) was performed in 95 (35.8%) cases and results were consistent or
      suspicious for a malignancy in 62 cases (65.2%). Endoscopic mucosal resection
      (EMR) was performed in 17 cases (6.41%) on the same session following
      endosonographic evaluation. The procedure was successful in all patients with no
      complications related to sedation, EUS, or EUS-FNA encountered. One patient had
      perforation following EMR. LIMITATION: Retrospective study. CONCLUSIONS: EUS and
      EUS-FNA are feasible and safe and have a significant impact on the management of
      GI, pancreatobiliary and mediastinal diseases in extreme elderly.

PMID- 21735088
TI  - Procalcitonin can be used as a marker of premature atherosclerosis in acromegaly.
AB  - The objective of the study was to evaluate arterial morphologic changes of early
      atherosclerosis and changes in procalcitonin (PCT) levels in patients with
      acromegaly according to disease activity. Thirty-three active and 20 inactive
      acromegaly patients followed at Endocrinology-Metabolism out-patient clinic of
      Cerrahpasa Medical Faculty between 2004 and 2008 were included in the study.
      Twenty gender and age matched healthy subjects were included as the control
      group. Intima-media thickness (IMT) of the carotid arteries was measured by
      ultrasonography. Blood was drawn for biochemical tests and the serum
      concentrations of C-reactive protein (CRP) and PCT. Intergroup analysis revealed
      no significant differences between Growth hormone (GH), insulin like growth
      factor-1 (IGF-1), and IMT (P = 0.42, P = 0.47 respectively). No significant
      differences were found in the fibrinogen, CRP and PCT levels of the acromegaly
      patients and the subjects in the control group (P = 0.57, P = 0.84, P = 0.68
      respectively). In the patients with IMT >= 1 mm, PCT (0.4 [IQR: 0.4-0.55]) levels
      were significantly different from the patients without atherosclerosis (0.06
      [IQR: 0.05-0.12], P < 0.001). The correlation between IMT and PCT (P = 0.001, r =
      0.47) was more significant than the correlation between IMT and CRP (P = 0.01, r
      = 0.28). There was a positive correlation between IMT and atherosclerotic risk
      factors such as age (P = 0.01, r = 0.27) and body mass index (BMI; P = 0.005, r =
      0.32). Our results showed that PCT increases before CRP and it can be useful for
      the assessment of premature atherosclerosis in acromegaly as well.

PMID- 21735089
TI  - Cognitive function in acromegaly: description and brain volumetric correlates.
AB  - In acromegaly, we reported on increased rates of affective disorders such as
      dysthymia and depression, as well as structural brain changes. Objective of this
      study was to determine if cognitive impairments in patients with acromegaly exist
      and whether such impairments are associated with structural brain alterations
      defined by magnetic resonance imaging (MRI). In this cross-sectional study, 55
      patients with biochemically confirmed acromegaly were enrolled. MRI data were
      compared with 87 control subjects. Main outcome measures were performance levels
      in 13 cognitive tests covering the domains of attention, memory and executive
      function, with performance below the cut-off level of the 16th percentile rated
      as impaired. In addition, individual global and hippocampal volume changes were
      defined for each patient in reference to a normative sample. We found that up to
      33.3% of the patients were impaired in the attention, up to 24.1% in the memory,
      and up to 16.7% in the executive function domain. 67.3% of the patients failed to
      reach the cut-off level in at least one subtest. MRI demonstrated increased
      global, left and right hippocampal grey matter and white matter, particularly
      early in the disease course. Rather few positive than expected negative
      correlations could be established between the hippocampal grey matter gain and
      cognitive performance. Cognitive dysfunction, particularly attentional deficits,
      are common in acromegaly, rendering neuropsychological testing essential in the
      diagnostic work-up.

PMID- 21735090
TI  - In vitro optimization of retinoic acid-induced neuritogenesis and TH endogenous
      expression in human SH-SY5Y neuroblastoma cells by the antioxidant Trolox.
AB  - Though, it is quite well-known how retinoic acid (RA) is able to induce
      neuritogenesis in different in vitro models, the putative role exerted by
      reactive oxygen species (ROS) during this process still need to be further
      studied. For such purpose, we used a neuronal-like cell line (SH-SY5Y cells) in
      order to investigate whether the antioxidant Trolox (a hydrophilic analog of
      alpha-tocopherol) could have any effect on the number of RA-induced neurites, and
      how significant changes in cellular redox homeostasis may affect the cellular
      endogenous expression of tyrosine hydroxylase (TH). Our results show a
      significant enhancement of RA (10 MUM)-induced neuritogenesis and TH endogenous
      expression, when cells were co-treated with Trolox (100 MUM) for 7 days.
      Moreover, this effect was associated with an improvement in cellular viability.
      The mechanism seems to mainly involve PI3 K/Akt rather than MEK signaling
      pathway. Therefore, our data demonstrate that concomitant decreases in basal
      reactive oxygen species (ROS) production could exert a positive effect on the
      neuritogenic process of RA-treated SH-SY5Y cells.

PMID- 21735091
TI  - The p23 co-chaperone protein is a novel substrate of CK2 in Arabidopsis.
AB  - The ubiquitous Ser/Thr protein kinase CK2, which phosphorylates hundreds of
      substrates and is essential for cell life, plays important roles also in plants;
      however, only few plant substrates have been identified so far. During a study
      aimed at identifying proteins targeted by CK2 in plant response to salicylic acid
      (SA), we found that the Arabidopsis co-chaperone protein p23 is a CK2 target,
      readily phosphorylated in vitro by human and maize CK2, being also a substrate
      for an endogenous casein kinase activity present in Arabidopsis extracts, which
      displays distinctive characteristics of protein kinase CK2. We also demonstrated
      that p23 and the catalytic subunit of CK2 interact in vitro and possibly in
      Arabidopsis mesophyll protoplasts, where they colocalize in the cytosol and in
      the nucleus. Although its exact function is presently unknown, p23 is considered
      a co-chaperone because of its ability to associate to the chaperone protein
      Hsp90; therefore, an involvement of p23 in plant signal transduction pathways,
      such as SA signaling, is highly conceivable, and its phosphorylation may
      represent a fine mechanism for the regulation of cellular responses.

PMID- 21735092
TI  - Cloning and purification of protein kinase CK2 recombinant alpha and beta
      subunits from the Mediterranean fly Ceratitis capitata.
AB  - The Mediterranean fruit fly Ceratitis capitata is an insect capable of wreaking
      extensive damage to a wide range of fruit crops. Protein kinase CK2 is a
      ubiquitous Ser/Thr kinase that is highly conserved among eukaryotes; it is a
      heterotetramer composed of two catalytic (alpha) and a dimer of regulatory (beta)
      subunits. We present here the construction of the cDNA molecules of the CK2alpha
      and CK2beta subunits from the medfly C. capitata by the 5'/3' RACE and RT-PCR
      methods, respectively. CcCK2alpha catalytic subunit presents the characteristic
      and conserved features of a typical protein kinase, similar to the regulatory
      CcCK2beta subunit, that also possess the conserved features of regulatory CK2beta
      subunits, as revealed by comparison of their predicted amino acid sequences with
      other eukaryotic species. The recombinant CcCK2alpha and CcCK2beta proteins were
      purified by affinity chromatography to homogeneity, after overexpression in
      Escherichia coli. CcCK2alpha is capable to utilize GTP and its activity and is
      inhibited by polyanions and stimulated by polycations in phosphorylation assays,
      using purified acidic ribosomal protein P1 as a substrate.

PMID- 21735093
TI  - CK2 functionally interacts with AKT/PKB to promote the beta-catenin-dependent
      expression of survivin and enhance cell survival.
AB  - beta-Catenin is crucial in the canonical Wnt signaling pathway. This pathway is
      up-regulated by CK2 which is associated with an enhanced expression of the
      antiapoptotic protein survivin, although the underlying molecular mechanism is
      unknown. AKT/PKB kinase phosphorylates and promotes beta-catenin transcriptional
      activity, whereas CK2 hyperactivates AKT by phosphorylation at Ser129; however,
      the role of this phosphorylation on beta-catenin transcriptional activity and
      cell survival is unclear. We studied in HEK-293T cells, the effect of CK2
      dependent hyperactivation of AKT on cell viability, as well as analyzed beta
      catenin subcellular localization and transcriptional activity and survivin
      expression. CK2alpha overexpression led to an augmented beta-catenin-dependent
      transcription and protein levels of survivin, and consequently an enhanced
      resistance to apoptosis. However, CK2alpha-enhancing effects were reversed when
      an AKT mutant deficient in Ser129 phosphorylation by CK2 was co-expressed.
      Therefore, our results strongly suggest that CK2alpha-specific enhancement of
      beta-catenin transcriptional activity as well as cell survival may depend on AKT
      hyperactivation by CK2.

PMID- 21735094
TI  - A detailed thermodynamic profile of cyclopentyl and isopropyl derivatives binding
      to CK2 kinase.
AB  - The detailed understanding of the molecular features of a ligand binding to a
      target protein, facilitates the successful design of potent and selective
      inhibitors. We present a case study of ATP-competitive kinase inhibitors that
      include a pyradine moiety. These compounds have  similar chemical structure,
      except for distinct terminal hydrophobic cyclopentyl or isopropyl groups, and
      block kinase activity of casein kinase 2 subunit alpha (CK2alpha), which is a
      target for several diseases, such as cancer and glomerulonephritis. Although
      these compounds display similar inhibitory potency against CK2alpha, the crystal
      structures reveal that the cyclopentyl derivative gains more favorable
      interactions compared with the isopropyl derivative, because of the additional
      ethylene moiety. The structural observations and biological data are consistent
      with the thermodynamic profiles of these inhibitors in binding to CK2alpha,
      revealing that the enthalpic advantage of the cyclopentyl derivative is
      accompanied with a lower entropic loss. Computational analyses indicated that the
      relative enthalpic gain of the cyclopentyl derivative arises from an enhancement
      of a wide range of van der Waals interactions from the whole complex. Conversely,
      the relative entropy loss of the cyclopentyl derivative arises from a decrease in
      the molecular fluctuation and higher conformational restriction in the active
      site of CK2alpha. These structural insights, in combination with thermodynamic
      and computational observations, should be helpful in developing potent and
      selective CK2alpha inhibitors.

PMID- 21735095
TI  - Protein kinase CK2 accumulation in "oncophilic" cells: causes and effects.
AB  - At variance with protein kinases expressed by oncogenes, CK2 is endowed with
      constitutive activity under normal conditions, and no CK2 gain-of-function
      mutants are known. Its amount, however, is abnormally high in malignant cells
      where it appears to be implicated in many of the cell biology phenomena
      associated with cancer. These observations can be reconciled assuming that tumor
      cells develop an overdue reliance ("non-oncogene addiction") on abnormally high
      CK2 level. While the potential of this latter to generate an environment
      favorable to neoplasia is consistent with the global antiapoptotic and
      prosurvival role played by CK2, it is not clear what is determining accumulation
      of CK2 in cells "predisposed" to become malignant. Exploiting the apoptosis
      sensitive (S) or resistant (R) CEM cell model, characterized by sharply different
      CK2 levels, we have now correlated the level and degradation rate of CK2 to those
      of the chaperone proteins Hsp90 and Cdc37. We show in particular that persistence
      of high CK2 level in R-CEM, as opposed to S-CEM, is accompanied by the presence
      of an immunospecific form of Cdc37 not detectable in S-CEM and refractory to
      staurosporine-induced degradation.

PMID- 21735096
TI  - CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor
      domain. Translational and clinical research.
AB  - CK2 represents an oncology target scientifically validated. However, clinical
      research with inhibitors of the CK2-mediated phosphorylation event is still
      insufficient to recognize it as a clinically validated target. CIGB-300, an
      investigational peptide-based drug that targets the phosphoaceptor site, binds to
      a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB
      300 proapoptotic effect is preceded by its nucleolar localization, inhibition of
      the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly.
      Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome
      biogenesis, cell proliferation, glycolisis, and cell motility in proteomic
      studies which helped to understand its mechanism of action. In the clinical
      ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human
      trial in women with cervical malignancies who also experienced signs of clinical
      benefit. In a second Phase 1 clinical trial in women with cervical cancer stage
      IB2/II, the MTD and DLT have been also identified in the clinical setting.
      Interestingly, in cervical tumors the B23/nucleophosmin protein levels were
      significantly reduced after CIGB-300 treatment at the nucleus compartment. In
      addition, expanded use of CIGB-300 in case studies has evidenced antitumor
      activity when administered as compassional option. Collectively, our data outline
      important clues on translational and clinical research from this novel peptide
      based drug reinforcing its perspectives to treat cancer and paving the way to
      validate CK2 as a promising target in oncology.

PMID- 21735097
TI  - Structure-based discovery of novel flavonol inhibitors of human protein kinase
      CK2.
AB  - Serine/threonine protein kinase CK2 controls vast variety of fundamental
      processes in cell life; however, despite long period of study, its functional
      role is not completely determined. CK2 has a significant pathogenic potential and
      its activity is strictly associated with the development of various kinds of
      disorders. There are a growing number of facts that inhibitors of CK2 could be
      used as pharmaceutical agents for the cancer treatment, viral infections, and
      inflammatory diseases. In this article, we report structural and biological data
      on the novel synthetic flavonol derivatives, 3-hydroxy-4'-carboxyflavones,
      possessing a high inhibitory activity toward CK2. With the aid of combinatorial
      organic synthesis, molecular modeling techniques and biochemical in vitro tests,
      we studied the structure-activity relationships of flavonol derivatives and
      developed binding model describing their key intermolecular interactions with the
      CK2 ATP-binding site. Obtained data show that the synthetic 3-hydroxy-4'
      carboxyflavones possess the highest activity among flavonol inhibitors of CK2
      known till date.

PMID- 21735098
TI  - PKCalpha take part in CCR7/NF-kappaB  autocrine signaling loop in CCR7-positive
      squamous cell carcinoma of head and neck.
AB  - Metastatic squamous cell carcinoma of head and neck (SCCHN) has been shown to
      express chemokine receptor 7 (CCR7). The role of nuclear factor-kappaB (NF
      kappaB) in propagating an autocrine signaling loop in CCR7-positive SCCHN cells
      may provide a clinically useful biomarker of disease status and response to
      therapy. In this article, we hypothesized that PKCalpha might be involved in the
      CCR7/NF-kappaB autocrine signaling loop. Results showed that CCL19 induced the
      activation of PKCalpha, and the increased activity of PKCalpha was abolished by
      CCR7 mAb. PKCalpha inhibition with Go6976 led to significant reduction in the
      activation and nuclear translocation of NF-kappaB induced by CCL19.
      Immunohistochemical assay also showed that CCR7 and PKCalpha were highly
      expressed in SCCHN and correlated with each other, which was significantly
      related to lymph node metastasis and clinical stage. Taken together, PKCalpha is
      involved in the CCR7/NF-kappaB autocrine signaling loop.

PMID- 21735099
TI  - Correlation between HIV disease and lipid metabolism in antiretroviral-naive HIV
      infected patients in Japan.
AB  - Antiretroviral therapy alters lipid metabolism in HIV-infected patients. However,
      interpreting the impact of HIV infection on lipid metabolism is difficult because
      of various associated factors, including antiretroviral drugs and demographic
      characteristics. A few studies have associated HIV infection with lipid
      metabolism in antiretroviral-naive HIV-infected patients. Because there were no
      data in this regard from Japan, the present study examined the impact of HIV
      infection, as well as demographic and clinical features, on lipid metabolism in
      antiretroviral-naive HIV-infected patients in Japan. We performed a cross
      sectional study to examine the impact of HIV disease, demographic and clinical
      characteristics on lipid metabolism among 168 HIV-infected Japanese men who were
      antiretroviral naive and who did not have hemophilia, including patients who took
      medication for dyslipidemia. The mean age of the patients was 45.7 years; 0.6% of
      the patients took medication to dyslipidemia. The mean CD4 lymphocyte count was
      289/MUL, the mean baseline log10 HIV viral load was 4.2 HIV-1 RNA copies/mL, and
      22% of the patients had a history of AIDS-defining events. A higher HDL-C
      concentration was associated with a higher CD4 lymphocyte count (p = 0.043).
      Also, a higher LDL-C concentration was associated with a higher CD4 lymphocyte
      count (p = 0.003). Infection with HIV was associated with dyslipidemia in
      antiretroviral-naive patients. More advanced HIV disease was associated with less
      favorable lipid homeostatic profiles. These results are similar to findings from
      other countries.

PMID- 21735100
TI  - Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and
      CXCR7.
AB  - The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in
      tumor invasion, proliferation and metastasis. Since both receptors are
      overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated
      their potential as targets for detection of cancers by molecular imaging. We
      synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye
      IRDye((r))800CW, tested their selectivity, sensitivity and biological activity in
      vitro and their feasibility to visualize tumors in vivo. Purified CXCL12
      conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7
      breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was
      time- and concentration-dependent, and the label could be competitively displaced
      by the native peptide. Control conjugates with bovine serum albumin or
      lactalbumin failed to label the cells. In mice, the conjugate distributed
      rapidly. After 1-92 h, subcutaneous tumors of human MCF-7 and A764 cells in
      immunodeficient mice were detected with high sensitivity. Background was observed
      in particular in liver within the first 24 h, but also skull and hind limbs
      yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and
      selective probes to detect solid and metastatic tumors by targeting tumor cells
      and tumor vasculature.

PMID- 21735101
TI  - The dual role of TLR3 in metastatic cell line.
AB  - Toll-like receptors (TLRs) are members of transmembrane proteins that recognize
      conserved molecular motifs of viral and bacterial origin and initiate innate
      immune response. As the role of TLRs in tumors cells is still not clear, our aim
      was to investigate the role of TLR3 in primary tumor and metastatic cells (SW480,
      SW620, FaDu and Detroit 562). We have reported here on the dual role of TLR3 in
      pharynx metastatic cell line (Detroit 562); on one hand TLR3 activation drove
      cells to apoptosis while on the other its stimulation contributed to tumor
      progression by altering the expression of tumor promoting genes (PLAUR, RORB) and
      enhancing the cell migration potential. In addition, we have shown TLR3 signaling
      pathway is functional in another metastatic cancer cell line (SW620) suggesting
      TLR3 might be important in the process of tumor metastasis. Since TLR3 agonists
      have been used in tumor therapy with the aim to activate immune system,
      scientific contribution of this work is drawing attention to the importance of
      further work on this topic, especially pro-tumor effect of TLR3, in order to
      avoid possible side-effects.

PMID- 21735102
TI  - Glutaredoxin 2a, a mitochondrial isoform, plays a protective role in a human cell
      line under serum deprivation.
AB  - The roles of mitochondrial glutaredoxin (Grx2a) under serum deprivation were
      assessed using the human stable HepG2 cell lines overexpressing or down
      regulating Grx2a. The Grx2a-overexpressing stable cells displayed enhanced
      proliferation, decreased reactive oxygen species (ROS) and caspase-3 activity
      levels, and increased total GSH level, compared to the vector control cells.
      These characteristics of the overexpressing stable cells were reversed by down
      regulating Grx2a in the same cell line. In the limited serum conditions, the
      Grx2a-overexpressing stable pcDNA3.0/HA-Grx2a cells exhibited higher cellular
      viabilities and total GSH level, and showed much lower enhancement in ROS and
      caspase-3 activity levels than the vector control pcDNA3.0/HA cells. However, the
      Grx2a-down-regulating stable cells gave rise to diminished cellular viabilities
      and further decreased total GSH level, and contained significantly higher ROS and
      caspase-3 activity levels, under serum deprivation than the vector control cells.
      These results suggest that Grx2a plays proliferative and anti-apoptotic roles
      under serum deprivation.

PMID- 21735103
TI  - Comparative analysis of genetic diversity in sacred lotus (Nelumbo nucifera
      Gaertn.) using AFLP and SSR markers.
AB  - The sacred lotus (Nelumbo nucifera Gaertn.) is an aquatic plant of economic and
      ornamental importance in China. In this study, we developed twenty novel sacred
      lotus SSR markers, and used AFLP and SSR markers to investigate the genetic
      diversity and genetic relationships among 58 accessions of N. nucifera including
      15 seed lotus, 12 rhizome lotus, 24 flower lotus and 7 wild lotus. Our results
      showed that sacred lotus exhibited a low level of genetic diversity, which may
      attribute to asexual reproduction and long-term artificial selection. A
      dendrogram based on both AFLP and SSR clustering data showed that: (1) the seed
      lotus accessions and rhizome lotus accessions were distinctly clustered into
      different groups, which indicated the significant genetic differentiation between
      them. This may be attributed to the two modes of reproduction and lack of genetic
      exchange; (2) the accessions of Thailand wild lotus were separated from other
      wild lotus accessions. This implied that the Thailand lotus might be genetically
      differentiated from other wild lotuses. In addition, Mantel test conducted gave
      highly significant correlation between AFLP-SSR data and each of the AFLP and SSR
      ones, with the values of r = 0.941 and r = 0.879, respectively, indicating the
      higher efficiency of the combination of these techniques (AFLP and SSR) in
      estimation and validation of the genetic diversity among the accession of sacred
      lotus. This knowledge of the genetic diversity and genetic relatedness of N.
      nucifera is potentially useful to improve the current strategies in breeding and
      germplasm conservation to enhance the ornamental and economic value of sacred
      lotus.

PMID- 21735104
TI  - Identification and analysis of MC4R polymorphisms and their association with
      economic traits of Korean cattle (Hanwoo).
AB  - Signaling by the melanocortin-4 receptor (MC4R) is important for mediation the
      effect of leptin on food intake and energy homeostasis, and is associated with
      obesity, energy homeostasis and control of feeding behavior. Presently, the
      bovine MC4R gene was characterized to detect genetic variation at this locus and
      to relate it to economic traits in Korean cattle (Hanwoo). Five single nucleotide
      polymorphisms (SNPs) were identified in the coding region (G709A, C927T, C1069G,
      C1343A, and C1786T). G709A changed amino acid 166 of the MC4R protein from valine
      to methionine and C1069G changed amino acid 286 of the MC4R protein from leucine
      to valine. A SNP at C927T significantly influenced the Marbling score, SNP
      markers C1069G and C1343A significantly affected the Backfat thickness, and the
      SNP marker C1786T significantly influenced backfat and Marbling score. The MC4R
      gene may thus be a candidate gene for carcass traits with MC4R SNPs being
      potentially valuable as genetic markers for economic traits in Hanwoo.

PMID- 21735105
TI  - TNF-308 gene polymorphism and tuberculosis susceptibility: a meta-analysis
      involving 18 studies.
AB  - A number of studies have investigated the association between TNF-308 (rs1800629
      G/A) polymorphisms and the susceptibility towards tuberculosis (TB) in different
      populations. However, many of these studies provided inconsistent results. In
      this study, a systematic review and meta-analysis of the published studies was
      performed to gain a clearer understanding of this association. The PubMed,
      Embase, Web of Science and CNKI databases were searched for case-control studies
      published up to Jan 2011, we used no lower date limit. Data were extracted and
      pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A
      total of 18 publications from 2001 to 2010, involving 2584 TB cases and 3817
      controls were included. Overall, for the A allele carriers (G/A + A/A) vs.
      homozygote GG, the pooled OR was 1.03 (95% CI = 0.89-1.19; P = 0.912 for
      heterogeneity). For the allele A vs. allele G, the pooled OR was 1.07 (95% CI =
      0.93-1.22; P = 0.013 for heterogeneity). In the stratified analysis by ethnicity,
      among Asians significant risk was found for allele A vs. allele G (OR = 1.22, 95%
      CI = 1.02-1.47; P = 0.152 for heterogeneity), no significant risks were found
      among Caucasians. This meta-analysis indicated that the TNF-308 polymorphism was
      not associated with the risk of TB in the total population, however the
      significant risk for TNF-308 A allele was found among Asians not Caucasians.

PMID- 21735106
TI  - Retinoic acid enhances skeletal myogenesis in human embryonic stem cells by
      expanding the premyogenic progenitor population.
AB  - Human embryonic stem cells (hESCs) are a potential source of material for cell
      therapy of muscle diseases. To date, it has proven difficult to generate skeletal
      muscle from hESCs in high yields and within a reasonable timeframe. Further, a
      hESC-derived Pax3/7-positive skeletal muscle progenitor population has not yet
      been described. Previous studies have shown that Pax3/7-positive progenitor cells
      can repopulate the satellite cell niche, indicating the importance of this
      population for therapy. We sought to optimize the differentiation of hESCs into
      skeletal muscle in order to characterize myogenesis at a molecular level and
      shorten the time course. We treated hESCs with retinoic acid (RA) and found an
      enhancement of skeletal myogenesis, and the expression of the myogenic regulatory
      factors (MRFs) MyoD and myogenin by day 25. Furthermore, we found that RA
      treatment expanded the muscle progenitor pool, which occurred as a distinct
      Pax3(+ve) population prior to MRF expression. Non-skeletal muscle tissue types
      were not significantly affected. Therefore, we have identified a differentiation
      pathway in hESCs that provides a skeletal muscle progenitor population which can
      undergo myogenesis more efficiently. We propose that RA could fit into a directed
      culture method for deriving skeletal muscle from hESCs.

PMID- 21735107
TI  - The use of drug-eluting stents versus bypass surgery for left main coronary
      artery disease.

PMID- 21735108
TI  - Amoebic liver abscess with negative serologic markers for Entamoeba histolytica:
      mind the gap!
AB  - A 38-year-old male German traveller returning from Asia presented with fever,
      night sweats and abdominal complaints. Abdominal ultrasonography revealed several
      fast-growing abscesses of the liver. Three blood cultures as well as serologic
      investigations for the detection of antibodies to Entamoeba histolytica,
      performed on day 3 and 7 after the onset of clinical symptoms, remained negative.
      Stool microscopy revealed the presence of amoeba cysts compatible with E.
      histolytica infection. Taking both the amoebic and bacterial etiology of the
      abscesses into consideration, the patient was treated with metronidazole and
      ciprofloxacin followed by paromomycin. Antibodies to E. histolytica tested
      positive shortly after anti-amoebic therapy was initiated. The patient fully
      recovered, and ultrasound follow-up showed complete resolution of the abscesses
      within 50 days. This case leads to the conclusion that amoebic liver abscess
      should be considered despite negative amoeba serology and that ultrasonography is
      an important diagnostic tool for the early diagnosis of extraintestinal
      amoebiasis.

PMID- 21735109
TI  - The reversed halo sign as the initial radiographic sign of pulmonary zygomycosis.
AB  - Zygomycosis is an emerging fungal infection that is associated with high
      mortality in hematological patients and stem cell transplantation (SCT)
      recipients. Radiology--computed tomography (CT) imaging in particular-
      facilitates the detection of lung involvement at an early stage of the infection.
      The reversed halo sign (RHS) has previously been reported in cryptogenetic
      organizing pneumonia and, more recently, as a manifestation of pulmonary
      zygomycosis. Here we describe a case of histologically proven zygomycosis due to
      Rhizopus microsporus in a SCT recipient. A chest CT scan performed on day +6 due
      to persistent fever unresponsive to antibiotics revealed the presence of the RHS,
      i.e., a focal ground-glass opacity mass surrounded by a solid ring of
      consolidation. The patient was treated with a combination of liposomal
      amphotericin B, caspofungin, and deferasirox, but subsequently developed a large
      pneumothorax and died on day +49 due to progressive infection. This case supports
      earlier observations that RHS may be an early radiological sign of zygomycosis,
      facilitating an aggressive diagnostic strategy.

PMID- 21735110
TI  - Oral histoplasmosis of a healthy man in a non-endemic area.

PMID- 21735111
TI  - A case of tuberculous meningitis with multiple intracranial tuberculomas and
      miliary tuberculosis and choroid tubercles.

PMID- 21735112
TI  - Lead (Pb)-inhibited radicle emergence in Brassica campestris involves alterations
      in starch-metabolizing enzymes.
AB  - Lead (Pb) is a toxic heavy metal released into the natural environment and known
      to cause oxidative damage and alter antioxidant mechanism in plants. However, not
      much is known about the interference of Pb with the biochemical processes and
      carbohydrate metabolism during seed germination. We, therefore, investigated the
      effect of Pb (50-500 MUM) upon biochemical alterations in germinating seeds (at
      24-h stage) of Brassica campestris L. Pb treatment significantly enhanced protein
      and carbohydrate contents that increased by ~43% and 200%, respectively, at 500
      MUM Pb over control. In contrast, the activities of starch/carbohydrate
      metabolizing enzymes--alpha-amylases, beta-amylases, acid invertases, and acid
      phosphatases--decreased by ~54%, 60%, 74%, and 52%, respectively, over control.
      Activities of peroxidases and polyphenol oxidases, involved in stress
      acclimation, however, increased by ~1.2- to 3.9-folds and 0.4- to 1.4-folds upon
      50-500-MUM Pb treatment. Pb enhanced oxidizing ability by 10 to 16.7 times over
      control suggesting interference with emerging root's oxidizing capacity. The
      study concludes that Pb exposure inhibits radicle emergence from B. campestris by
      interfering with the biochemical processes linked to protein and starch
      metabolism.

PMID- 21735113
TI  - Chemical elements in organic and conventional sweet oranges.
AB  - This work focuses on the determination of chemical elements in sweet oranges of
      variety Valencia produced under organic and conventional systems using
      instrumental neutron activation analysis and inductively coupled plasma mass
      spectrometry. The distribution of chemical elements was variable among the fruit
      parts with usually higher concentrations of Br, Ca, Ce, K, La, Na, Rb, and Sc in
      the peel. However, K, Na, and Rb also presented high values in the juice samples,
      while Fe and Zn were higher in the seeds. Differences between organic and
      conventional oranges were found for Br and Cu.

PMID- 21735114
TI  - Brain metastases from breast cancer: proposition of new prognostic score
      including molecular subtypes and treatment.
AB  - To develop a specific prognostic score for patients with brain metastases (BM)
      from breast cancer (BC), including the BC molecular subtype and treatment
      parameters, we analyzed the outcome of 130 patients with BM from BC who received
      whole-brain radiotherapy. We identified hierarchical risk groups for estimated
      survival by using recursive partitioning analysis (RPA). Seven prognostic
      factors, namely performance status, age, trastuzumab-based therapy for HER-2
      overexpressing tumors, a triple-negative phenotype, Scarff-Bloom-Richardson
      grade, the serum LDH level and the lymphocyte count at BM diagnosis, were
      incorporated in the RPA. The final RPA nodes were grouped according to the
      survival time. The RPA tree showed that survival was best (median 19.5 months)
      among patients with HER2-overexpressing tumors who received trastuzumab-based
      therapy. The worst survival (median 3.5 months) was observed among patients who
      did not receive trastuzumab and who had lymphopenia at BM diagnosis, or KPS <70
      and age over 50 years, or KPS >=70 and a triple-negative tumor (HR- & HER-2-).
      The other patients had a median survival of 12.5 months (P < 0.001). This 3-class
      specific prognostic score successfully predicted the outcomes of a heterogeneous
      group of patients with brain metastases from BC.

PMID- 21735115
TI  - Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/beta-catenin
      signaling.
AB  - Medulloblastoma is one of the leading causes of morbidity and mortality in
      pediatric cancer. Wnt-active tumors, an independent molecular subgroup in
      medulloblastoma, are characterized by a distinct pattern of genomic aberrations.
      We assessed the anticancer activity of cantharidin and norcantharidin against
      medulloblastoma, as cell lines in vitro and in athymic nude mice in vivo.
      Cantharidin and norcantharidin treatment impaired the growth of DAOY and UW228
      medulloblastoma cells and promoted the loss of beta-catenin activation and the
      beta-catenin nuclearization linked to N-cadherin impairment in vitro. Intra
      peritoneal administration of norcantharidin inhibited the growth of intra
      cerebellum tumors in orthotopic xenograft nude mice. Analysis of the xenograft
      tissues revealed enhanced neuronal differentiation and reduced beta-catenin
      expression. Our findings suggest that norcantharidin has potential therapeutic
      applications in the treatment of medulloblastoma as a result of its ability to
      cross the blood-brain barrier and its impairment of Wnt-beta-catenin signaling.

PMID- 21735116
TI  - Prognostic value of novel biomarkers in astrocytic brain tumors: nuclear receptor
      co-regulators AIB1, TIF2, and PELP1 are associated with high tumor grade and
      worse patient prognosis.
AB  - Estrogen receptors alpha (ERalpha) and beta (ERbeta) and their co-regulatory
      proteins are key components of complex signaling networks that specifically
      regulate the growth and development of various tissues and tumors. Still, their
      protein expression profiles and possible role in the pathogenesis of astrocytic
      tumors remain largely unknown. The purpose of the present study is to evaluate
      the differential protein expression of EpsilonRalpha, ERbeta, and their co
      activators, AIB1, TIF2, and PELP1 in astrocytic tumors of World Health
      Organization (WHO) grade II-IV, using immunohistochemistry. Potential
      correlations with clinicopathological parameters and patient prognosis were also
      explored. ERalpha protein expression was undetectable while ERbeta levels were
      significantly decreased with progression of tumor grade (P < 0.001). High
      expression of ERbeta was an independent favorable prognostic factor on
      multivariate analysis (P = 0.003). Expression of AIB1, TIF2, and PELP1 was not
      correlated with ERbeta expression and followed an opposite trend, with increasing
      levels in high-grade relative to low-grade tumors (P < 0.001). Univariate
      survival analysis revealed that high AIB1, TIF2, and PELP1 expression was
      associated with worse prognosis (P = 0.049, P = 0.033, and P = 0.020,
      respectively). ERbeta and ER co-activators AIB1, TIF2, and PELP1 appear to play
      an important role in the pathogenesis and progression of astrocytic tumors and
      might have prognostic significance. The mechanisms underlying their involvement
      in astrocytic tumorigenesis, as well as their utility for prognostic and
      therapeutic purposes merit further investigation.

PMID- 21735117
TI  - A phase I trial of the farnesyl transferase inhibitor, SCH 66336, with
      temozolomide for patients with malignant glioma.
AB  - We conducted a phase I clinical trial of the combination of SCH 66336 with
      temozolomide administered on the standard 5-day dosing schedule. The primary
      objective was to determine the maximum tolerated dose and dose limiting toxicity
      (DLT) of twice daily SCH 66336 when administered with temozolomide to adults with
      malignant glioma previously treated with radiation therapy. Patients were
      enrolled to two strata: stratum A, patients not on enzyme-inducing antiepileptic
      drugs (EIAEDs); stratum B, patients receiving EIAEDs. Temozolomide was
      administered at a dose of 150 mg/m(2) daily for five days for the first 28-day
      cycle and escalated to 200 mg/m(2), during subsequent cycles. SCH 66336 was
      administered twice daily on a continuous daily dosing schedule. The starting dose
      of SCH 66336 was 75 mg twice daily for stratum A and 125 mg twice daily for
      stratum B. Cohorts of 3-6 patients were treated per dose level until DLT was
      observed. Thirty six patients were enrolled on study, including 21 patients on
      stratum A and 15 on stratum B. All DLTs were grade 3 events and included hepatic,
      gastrointestinal, renal, thrombotic and constitutional events. No grade 4 or 5
      toxicities were observed. The phase II dose of SCH 66336 when combined with
      temozolomide is 150 mg twice daily for patients not on EIAEDs and 175 mg twice
      daily for patients on EIAEDs.

PMID- 21735118
TI  - Treatment of hypertension in Germany: is there a social gradient?
AB  - OBJECTIVES: Effective hypertension control remains low without much improvement
      since the 1990s. However, information is limited whether and how social status
      impacts on hypertension control. METHODS: Data from the German Health Survey 1998
      are used to explore the role of social status according to educational
      achievement in treating hypertension, adjusted for key determinants in a logistic
      regression. RESULTS: Actual as well as population prevalence (>=140 mmHg/>=90
      mmHg) is highest in the lowest of the three social classes with 59.4 and 51.9% as
      compared to 44.5 and 40.5% in the highest. Physician contacts during the previous
      year were also highest in the lower class with 76.0% as compared to 59.0% in the
      highest. The logistic regression revealed insignificant odds ratios (OR) of 1.46
      for the highest and 1.12 for the middle class for treatment of known hypertension
      after adjusting for gender (OR for females, 1.38), age (OR for 60-69 years,
      13.13), GP visits (OR, 1.43) and living in East Germany (OR, 1.56). CONCLUSIONS:
      German survey data for antihypertensive treatment do not show any significant
      disadvantage for the lowest social class.

PMID- 21735119
TI  - Theoretical study of GSK-3alpha: neural networks QSAR studies for the design of
      new inhibitors using 2D descriptors.
AB  - Glycogen synthase kinase-3 (GSK-3) targets encompass proteins implicated in AD
      and neurological disorders. The functions of GSK-3 and its implication in various
      human diseases have triggered an active search for potent and selective GSK-3
      inhibitors. In this sense, QSAR could play an important role in studying these
      GSK-3 inhibitors. For this reason, we developed QSAR models for GSK-3alpha,
      linear discriminant analysis (LDA), and artificial neural networks (ANNs) from
      nearly 50,000 cases with more than 700 different GSK-3alpha inhibitors obtained
      from ChEMBL database server; in total we used more than 20,000 different
      molecules to develop the QSAR models. The model correctly classified 237 out of
      275 active compounds (86.2%) and 14,870 out of 15,970 non-active compounds
      (93.2%) in the training series. The overall training performance was 93.0%.
      Validation of the model was carried out using an external predicting series. In
      these series, the model classified correctly 458 out of 549 (83.4%) compounds and
      29,637 out of 31,927 non-active compounds (83.4%). The overall predictability
      performance was 92.7%. In this study, we propose three types of non-linear ANN as
      alternative to already existing models, such as LDA. Linear neural network: LNN:
      236:236-1-1:1 which had an overall training performance of 96% proved to be the
      best model. In addition, we did a study of the different fragments of the
      molecules of the database to see which fragments had more influence in the
      activity. This can help design new inhibitors of GSK-3alpha. This study reports
      the attempts to calculate, within a unified framework probabilities of GSK-3alpha
      inhibitors against different molecules found in the literature.

PMID- 21735120
TI  - 1H, 13C, and 15N assignments of wild-type human gammaS-crystallin and its
      cataract-related variant gammaS-G18V.
AB  - We present the backbone and sidechain NMR assignments and a structural analysis
      of the 178-residue wild-type gammaS-crystallin and the cataract-related point
      mutant, gammaS-G18V. gammaS-crystallin is a structural component of the eye lens,
      which maintains its solubility and stability over many years. NMR assignments and
      continued structural investigations of gammaS-crystallin and aggregation-prone
      variants will advance understanding of cataract formation.

PMID- 21735121
TI  - Density functional theory analysis of carbonyl sulfide hydrolysis: effect of
      solvation and nucleophile variation.
AB  - The detailed mechanisms of the hydrolysis of carbonyl sulfide (OCS) by
      nucleophilic water and hydroxide ion in both the gas phase and bulk water solvent
      have been investigated using density functional theory. Various reaction channels
      on the potential surface have been identified. The thermodynamic results
      demonstrate that the hydrolysis of OCS by nucleophilic water and hydroxide ion
      should proceed more favorably at low temperature. The hydrolysis of OCS by the
      hydroxide ion is the main reaction channel from thermodynamic and kinetic
      perspectives, and the bulk solvent can influence the rate-determining step in
      this channel. However, the solvent barely modifies the activation energy of the
      rate-determining step. For the hydrolysis of OCS by nucleophilic water, the
      solvent does not modify the rate-determining step, and the corresponding
      activation energy of the rate-determining step barely changes. This bulk solvent
      effect suggests that most of the contribution of the solvent is accounted for by
      considering one water molecule and a hydroxide ion.

PMID- 21735122
TI  - Evaluation of natural and nitramine binding energies to 3-D models of the S1S2
      domains in the N-methyl-D-aspartate receptor.
AB  - Overactivation of the N-methyl-D-aspartate receptor (NMDAR) in postsynaptic
      neurons leads to glutamate-related excitotoxicity in the central nervous system
      of mammals. We have built 3-D models of each domain for the universal screening
      of potential toxicants and their binding mechanisms. Our docking results show
      that the calculated pK (i) values of glycine and L: -glutamate significantly
      increase (>1) when the NR1 and NR2A S1S2 domains are closing, respectively.
      Inversely, D: -cycloserine (DCS) and 5,7-dichlorokynurenic acid (5,7-DCKA) do not
      show such a dependence on domain closure. Replica exchange molecular dynamics
      (REMD) confirmed 5 different conformational states of the S1S2 domain along the
      308.2 K temperature trajectory. Analysis of residue fluctuations during this
      temperature trajectory showed that residues in loop 1, loop 2, the amino terminal
      domain (ATD), and the area linked to ion channel alpha-helices are involved in
      this movement. This further implicates the notion that efficacious ligands act
      through S1S2 lobe movement which can culminate in the opening or closing of the
      ion channel. We further tested this by docking hexahydro-1,3,5-trinitro-1,3,5
      triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) to the
      S1S2 domain. Our results predict that these nitramines are not efficacious and
      thus do not produce excitoxicity when they bind to the S1S2 domain of the NMDAR.

PMID- 21735123
TI  - A combined experimental and computational study on the material properties of
      shape memory polyurethane.
AB  - A type of shape memory polyurethane with 60 wt% hard segments (SMPU60) was
      prepared. Its material properties were tested by dynamic mechanical analysis
      (DMA) and Instron, and simulated using fully atomistic molecular dynamics (MD).
      The glass transition temperature (T (g)) of SMPU60 determined by DMA is 316 K,
      which is slightly lower than that estimated through MD simulations (T (g) = 328
      K) , showing the calculated T ( g ) is in good agreement with experimental data.
      A complex hydrogen bonding network was revealed with the calculation of radial
      distribution functions (RDFs). The C?O?H bond is the predominant hydrogen-bonding
      interaction. With increasing temperature, both the hydrogen bonding and the
      moduli decreased, and the dissociation of intermolecular hydrogen bonding induced
      the decrease of the moduli.

PMID- 21735124
TI  - Assessment of mercury bioaccumulation within the pelagic food web of lakes in the
      western Great Lakes region.
AB  - While mercury is a health hazard to humans and wildlife, the biogeochemical
      processes responsible for its bioaccumulation in pelagic food webs are still
      being examined. Previous studies have indicated both "bottom-up" control of
      piscivorous fish Hg content through methylmercury.(MeHg) supply, as well as site
      specific trophic factors. We evaluated ten studies from the western Great Lakes
      region to examine the similarity of MeHg trophic transfer efficiency within the
      pelagic food web, and assessed regional-scale spatial variability. Analyses of
      bioaccumulation and biomagnification factors between water, seston, zooplankton,
      and preyfish indicated that the largest increases in MeHg occurred at the base of
      the food web, and that the relative extent of trophic transfer was similar
      between sites. Positive correlations were observed between aqueous unfiltered
      MeHg, total Hg, and dissolved organic carbon, and measures of the efficiency of
      MeHg trophic transfer were consistent across widely disparate systems (both
      natural and experimentally manipulated) throughout North America. Such similarity
      suggests that the aqueous supply of MeHg is largely controlling bioaccumulation
      in pelagic food webs, while local, lake-specific variability can result from an
      array of trophic (biological) factors.

PMID- 21735125
TI  - Mercury exposure and neurochemical impacts in bald eagles across several Great
      Lakes states.
AB  - In this study, we assessed mercury (Hg) exposure in several tissues (brain,
      liver, and breast and primary feathers) in bald eagles (Haliaeetus leucocephalus)
      collected from across five Great Lakes states (Iowa, Michigan, Minnesota, Ohio,
      and Wisconsin) between 2002-2010, and assessed relationships between brain Hg and
      neurochemical receptors (NMDA and GABA(A)) and enzymes (glutamine synthetase (GS)
      and glutamic acid decarboxylase (GAD)). Brain total Hg (THg) levels (dry weight
      basis) averaged 2.80 MUg/g (range: 0.2-34.01), and levels were highest in
      Michigan birds. THg levels in liver (r(p) = 0.805) and breast feathers (r(p) =
      0.611) significantly correlated with those in brain. Brain Hg was not associated
      with binding to the GABA(A) receptor. Brain THg and inorganic Hg (IHg) were
      significantly positively correlated with GS activity (THg r(p) = 0.190; IHg r(p)
      = 0.188) and negatively correlated with NMDA receptor levels (THg r(p) = -0245;
      IHg r(p) = -0.282), and IHg was negatively correlated with GAD activity (r(s) = 
      0.196). We also report upon Hg demethylation and relationships between Hg and Se
      in brain and liver. These results suggest that bald eagles in the Great Lakes
      region are exposed to Hg at levels capable of causing subclinical neurological
      damage, and that when tissue burdens are related to proposed avian thresholds
      approximately 14-27% of eagles studied here may be at risk.

PMID- 21735126
TI  - A survey of environmental pollutants and cellular-stress markers of Porites
      astreoides at six sites in St. John, U.S. Virgin Islands.
AB  - Coral communities along the coast of St. John, U.S. Virgin Islands have exhibited
      site-specific behavior in declines. In order to determine if these specific coral
      communities are stressed and whether a pollutant or environmental factor present
      at this site is a probable stressor, we surveyed six near-shore coral communities
      in St. John, USVI for environmental pollutants and to determine the cellular
      physiological condition of the coral, Porites astreoides. The six sites within
      St. John are Cruz Bay, Caneel Bay, Hawksnest Bay, Trunk Bay, Tektite Reef in
      Beehive Bay, and Red Point. Red Point was considered the reference site because
      of its abundance and diversity of species, and it was the furthest removed from
      down-stream and down-current anthropogenic activities. All sites showed distinct
      cellular-stress marker patterns, indicating that the physiological condition of
      each population was different. Populations at Cruz, Hawksnest, Trunk, and Tektite
      were stressed, as indicated by high levels of DNA lesions and expression of
      stress proteins. Hawksnest and Tektite were contaminated with polyaromatic
      hydrocarbons (PAHs), while Cruz was contaminated with semi-volatile
      organochlorines and nitrogen-based biocides. At least for Hawksnest and Tektite,
      stress-marker patterns were consistent with an exposure to PAHs. Fecal coliform
      levels were high in Cruz and Trunk, indicating fecal contamination, as well as
      consideration for management action. Results from this study serve as a
      justification for a more thorough and methodical investigation into the stressors
      responsible for declines of coral populations within St. John. Furthermore, this
      study supports the argument for the importance of local factors contributing to
      regional coral reef declines; that not all forces impacting coral are global.

PMID- 21735127
TI  - Mangrove trees affect the community structure and distribution of anammox
      bacteria at an anthropogenic-polluted mangrove in the Pearl River Delta reflected
      by 16S rRNA and hydrazine oxidoreductase (HZO) encoding gene analyses.
AB  - Anaerobic ammonium oxidizing (anammox) bacterial community structures were
      investigated in surface (1-2 cm) and lower (20-21 cm) layers of mangrove
      sediments at sites located immediately to the mangrove trees (S0), 10 m (S1) and
      1000 m (S2) away from mangrove trees in a polluted area of the Pearl River Delta.
      At S0, both 16S rRNA and hydrazine oxidoreductase (HZO) encoding genes of anammox
      bacteria showed high diversity in lower layer sediments, but they were not
      detectable in lower layer sediments in mangrove forest. S1 and S2 shared similar
      anammox bacteria communities in both surface and lower layers, which were quite
      different from that of S0. At all three locations, higher richness of anammox
      bacteria was detected in the surface layer than the lower layer; 16S rRNA genes
      revealed anammox bacteria were composed by four phylogenetic clusters affiliated
      with the "Scalindua" genus, and one group related to the potential anammox
      bacteria; while the hzo genes showed that in addition to sequences related to the
      "Scalindua", sequences affiliated with genera of "Kuenenia", "Brocadia", and
      "Jettenia" were also detected in mangrove sediments. Furthermore, hzo gene
      abundances decreased from 36.5 * 10(4) to 11.0 * 10(4) copies/gram dry sediment
      in lower layer sediments while increased from below detection limit to 31.5 *
      10(4) copies/gram dry sediment in lower layer sediments from S0 to S2. The
      results indicated that anammox bacteria communities might be strongly influenced
      by mangrove trees. In addition, the correlation analysis showed the redox
      potential and the molar ratio of ammonium to nitrite in sediments might be
      important factors affecting the diversity and distribution of anammox bacteria in
      mangrove sediments.

PMID- 21735128
TI  - Influence of glucose concentration on the membrane stability of human
      erythrocytes.
AB  - The action of glucose as an osmolyte in relation to blood cells is not well
      characterized in the literature. This study aimed to study the influence of
      glucose concentration on the stability of red blood cells. The stability of
      erythrocytes was evaluated by the half-transition point obtained from the curves
      of lysis induced by glucose in the absence of salt or by increase in medium
      hypotonicity in the absence and the presence of different concentrations of
      glucose. In the presence of 0.9 g/dl NaCl, there was no hemolysis with increasing
      concentration of glucose from 0 to 10 g/dl. In the absence of NaCl, the
      dependence of hemolysis with the 0-10 g/dl glucose was described by a decreasing
      sigmoid, with fully lysed and fully protected cells being encountered in the
      presence of 0-2 and 4-10 g/dl glucose, respectively. The possible origin of such
      stabilization effect is discussed with base of what is known about
      osmostabilization of biological complexes and about the influence of glucose on
      the rheological properties of erythrocytes.

PMID- 21735129
TI  - Conformational preferences of modified nucleoside N(2)-methylguanosine (m(2)G)
      and its derivative N(2), N(2)-dimethylguanosine (m(2)(2)G) occur at 26th position
      (hinge region) in tRNA.
AB  - Conformational preferences of the modified nucleosides N(2)-methylguanosine
      (m(2)G) and N(2), N(2)-dimethylguanosine (m(2)(2)G) have been studied
      theoretically by using quantum chemical perturbative configuration interaction
      with localized orbitals (PCILO) method. Automated complete geometry optimization
      using semiempirical quantum chemical RM1, along with ab initio molecular orbital
      Hartree-Fock (HF-SCF), and density functional theory (DFT) calculations has also
      been made to compare the salient features. Single-point energy calculation
      studies have been made on various models of m(2)G26:C/A/U44 and
      m(2)(2)G26:C/A/U44. The glycosyl torsion angle prefers "syn" (chi = 286 degrees )
      conformation for m(2)G and m(2)(2)G molecules. These conformations are stabilized
      by N(3)-HC2' and N(3)-HC3' by replacing weak interaction between O5'-HC(8). The
      N(2)-methyl substituent of (m(2)G26) prefers "proximal" or s-trans conformation.
      It may also prefer "distal" or s-cis conformation that allows base pairing with
      A/U44 instead of C at the hinge region. Thus, N(2)-methyl group of m(2)G may have
      energetically two stable s-trans m(2)G:C/A/U or s-cis m(2)G:A/U rotamers. This
      could be because of free rotations around C-N bond. Similarly, N(2), N(2)
      dimethyl substituent of (m(2)(2)G) prefers "distal" conformation that may allow
      base pairing with A/U instead of C at 44th position. Such orientations of m(2)G
      and m(2)(2)G could play an important role in base-stacking interactions at the
      hinge region of tRNA during protein biosynthesis process.

PMID- 21735130
TI  - Glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide
      pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and
      mannosidase (MAN2B2) metabolism computational network analysis between chimpanzee
      and human left cerebrum.
AB  - We identified significantly higher expression of the genes glycogen debranching
      enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1),
      glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) from human left
      cerebrums versus chimpanzees. Yet the distinct low- and high-expression AGL,
      ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism networks between chimpanzee and
      human left cerebrum remain to be elucidated. Here, we constructed low- and high
      expression activated and inhibited upstream and downstream AGL, ENOSF1, ENPP2_1,
      GSTM3_3 and MAN2B2 metabolism network between chimpanzee and human left cerebrum
      in GEO data set by gene regulatory network inference method based on linear
      programming and decomposition procedure, under covering AGL, ENOSF1, ENPP2_1,
      GSTM3_3 and MAN2B2 pathway and matching metabolism enrichment analysis by
      CapitalBio MAS 3.0 integration of public databases, including Gene Ontology,
      KEGG, BioCarta, GenMapp, Intact, UniGene, OMIM, etc. Our results show that the
      AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network has more activated
      and less inhibited molecules in chimpanzee, but less activated and more inhibited
      in the human left cerebrum. We inferred stronger carbohydrate, glutathione and
      proteoglycan metabolism, ATPase activity, but weaker base excision repair,
      arachidonic acid and drug metabolism as a result of inducing cell growth in low
      expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of
      chimpanzee left cerebrum; whereas stronger lipid metabolism, amino acid
      catabolism, DNA repair but weaker inflammatory response, cell proliferation,
      glutathione and carbohydrate metabolism as a result of inducing cell
      differentiation in high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2
      metabolism network of human left cerebrum. Our inferences are consistent with
      recent reports and computational activation and inhibition gene number patterns,
      respectively.

PMID- 21735131
TI  - The co-expression of USP22 and BMI-1 may promote cancer progression and predict
      therapy failure in gastric carcinoma.
AB  - Recent experimental evidence support the model in which the simultaneous
      induction of BMI-1 and USP22 is critical during cancer progression. Whether this
      model may affect gastric cancer (GC) progression is worthy of additional study.
      In this study, we examined the significance of the USP22 and BMI-1 expression in
      GC (n = 219), non-cancerous mucosa (n = 37), and lymph node metastasis (n = 37).
      The protein expression level of USP22 and BMI-1 were concomitantly up-regulated
      from non-cancerous mucosa to primary carcinoma and from carcinomas to lymph node
      metastasis (P < 0.001). A statistical correlation was observed between USP22 and
      BMI-1 expression in GC tissues (n = 219, r = 0.634, P < 0.001) and in lymph node
      metastasis (n = 37, r = 0.689, P < 0.001). The incidence of positive expression
      was 57.08% for USP22, 49.32% for BMI-1, and 45.21% for USP22/BMI-1 in 219 GC
      tissues, respectively. Co-positive of USP22/BMI-1 was significantly correlated
      with gross features (x(2) = 14.256, P < 0.001), differentiation (x(2) = 5.872, P
      = 0.015), pT classification (x(2) = 18.486, P < 0.001), pN classification (x(2) =
      9.604, P = 0.002), pM classification (x(2) = 32.766, P < 0.001), and AJCC stage
      (x(2) = 58.278, P < 0.001). Notably, high USP22/BMI-1 expression was
      significantly associated with shorter disease-specific survival (P < 0.001). By
      Cox regression analysis, co-positive of USP22/BMI-1 was found to be an
      independent prognostic factor (P = 0.002). Our results indicated the simultaneous
      activation of USP22 and BMI-1 may associate with GC progression and therapy
      failure.

PMID- 21735132
TI  - In vitro model of bacterial biofilm formation on polyvinyl chloride biomaterial.
AB  - The aim of the study was to establish an in vitro model of Staphylococcus
      epidermidis biofilms on polyvinyl chloride (PVC) material, and to investigate
      bacterial biofilm formation and its structure using the combined approach of
      confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM).
      Staphylococcus epidermidis bacteria (stain RP62A) were incubated with PVC pieces
      in Tris buffered saline to form biofilms. Biofilm formation was examined at 6,
      12, 18, 24, 30, and 48 h. Thicknesses of these biofilms and the number, and
      percentage of viable cells in biofilms were measured. CT scan images of biofilms
      were obtained using CLSM and environmental SEM. The results of this study showed
      that Staphylococcus epidermidis biofilm is a highly organized multi-cellular
      structure. The biofilm is constituted of large number of viable and dead
      bacterial cells. Bacterial biofilm formation on the surface of PVC material was
      found to be a dynamic process with maximal thickness being attained at 12-18 h.
      These biofilms became mature by 24 h. There was significant difference in the
      percentage of viable cells along with interior, middle, and outer layers of
      biofilms (P < 0.05). Staphylococcus epidermidis biofilm is sophisticated in
      structure and the combination method involving CLSM and SEM was ideal for
      investigation of biofilms on PVC material.

PMID- 21735133
TI  - Down-regulation of tumor-associated NADH oxidase, tNOX (ENOX2), enhances
      capsaicin-induced inhibition of gastric cancer cell growth.
AB  - Gastric cancer is a common human malignancy and a major contributor to cancer
      related deaths worldwide. Unfortunately, the prognosis of most gastric cancer
      patients is poor because they are generally diagnosed at a late stage after the
      cancer has already metastasized. Most current research, therefore, emphasizes
      selective targeting of cancer cells by apoptosis-inducing agents. One such
      therapeutic agent is capsaicin, a component of chili peppers that has been shown
      to possess anti-growth activity against various cancer cell lines. Here, we
      examined the effect of capsaicin on SNU-1 and TMC-1 gastric cancer cells and
      found differing outcomes between the two cell lines. Our results show that
      capsaicin induced significant cytotoxicity with increases in oxidative stress,
      PARP cleavage, and apoptosis in sensitive SNU-1 cells. In contrast, TMC-1 cells
      were much less sensitive to capsaicin, exhibiting low cytotoxicity and very
      little apoptosis in response to capsaicin treatment. Capsaicin-induced apoptosis
      in SNU-1 cells was associated with down-regulation of tumor-associated NADH
      oxidase (tNOX) mRNA and protein. On the contrary, tNOX expression was scarcely
      affected by capsaicin in TMC-1 cells. We further showed that tNOX-knockdown
      sensitized TMC-1 cells to capsaicin-induced apoptosis and G1 phase accumulation,
      and led to decreased cell growth, demonstrating that tNOX is essential for cancer
      cell growth. Collectively, these results indicate that capsaicin induces
      divergent effects of the growth of gastric cancer cells that parallel its effects
      on tNOX expression, and demonstrate that forced tNOX down-regulation restored
      capsaicin-induced growth inhibition in TMC-1 cells.

PMID- 21735134
TI  - Combined survival analysis of cardiac patients by a Cox PH model and a Markov
      chain.
AB  - The control and treatment of dyslipidemia is a major public health challenge,
      particularly for patients with coronary heart diseases. In this paper we propose
      a framework for survival analysis of patients who had a major cardiac event,
      focusing on assessment of the effect of changing LDL-cholesterol level and
      statins consumption on survival. This framework includes a Cox PH model and a
      Markov chain, and combines their results into reinforced conclusions regarding
      the factors that affect survival time. We prospectively studied 2,277 cardiac
      patients, and the results show high congruence between the Markov model and the
      PH model; both evidence that diabetes, history of stroke, peripheral vascular
      disease and smoking significantly increase hazard rate and reduce survival time.
      On the other hand, statin consumption is correlated with a lower hazard rate and
      longer survival time in both models. The role of such a framework in
      understanding the therapeutic behavior of patients and implementing effective
      secondary and primary prevention of heart diseases is discussed here.

PMID- 21735135
TI  - A time scaling approach to develop an in vitro-in vivo correlation (IVIVC) model
      using a convolution-based technique.
AB  - In vitro-in vivo correlation (IVIVC) models prove very useful during drug
      formulation development, the setting of dissolution specifications and bio-waiver
      applications following post approval changes. A convolution-based population
      approach for developing an IVIVC has recently been proposed as an alternative to
      traditional deconvolution based methods, which pose some statistical concerns.
      Our aim in this study was to use a time-scaling approach using a convolution
      based technique to successfully develop an IVIVC model for a drug with quite
      different in vitro and in vivo time scales. The in vitro and the in vivo data
      were longitudinal in nature with considerable between subject variation in the in
      vivo data. The model was successfully developed and fitted to the data using the
      NONMEM package. Model utility was assessed by comparing model-predicted plasma
      concentration-time profiles with the observed in vivo profiles. This comparison
      met validation criteria for both internal and external predictability as set out
      by the regulatory authorities. This study demonstrates that a time-scaling
      approach may prove useful when attempting to develop an IVIVC for data with the
      aforementioned properties. It also demonstrates that the convolution-based
      population approach is quite versatile and that it is capable of producing an
      IVIVC model with a big difference between the in vitro and in vivo time scales.

PMID- 21735136
TI  - An active fraction of Achyranthes bidentata polypeptides prevents apoptosis
      induced by serum deprivation in SH-SY5Y cells through activation of
      PI3K/Akt/Gsk3beta pathways.
AB  - Achyranthes bidentata Blume is a commonly prescribed Chinese medicinal herb. Our
      previous studies have proved the neuroprotective function of Achyranthes
      bidentata polypeptides (ABPP), a major constituent from aqueous extracts of the
      herb. Now we have separated an active fraction, referred to as ABPP-E4, from ABPP
      by HPLC methods. This study aimed to investigate the possible therapeutic
      potential of ABPP-E4. Assessments of cell viability and apoptosis indicated that
      ABPP-E4 pretreatment, in a concentration-dependent manner, antagonized the cell
      viability loss and cell apoptosis of cultured SH-SY5Y cells deprived of serum.
      ABPP-E4 pretreatment also resulted in increase of Bcl-2/Bax ratio and inhibition
      of caspase-3 activation in the cells on exposure to serum deprivation. Signaling
      pathway analysis indicated that ABPP-E4 treatment stimulated the activation of
      Akt/Gsk3beta signaling in cultured SH-SY5Y cells, and anti-apoptotic effects of
      ABPP-E4 could be blocked by chemical inhibition of PI3K. Taken together, all the
      results suggest that ABPP-E4 might exert protective effects against serum
      deprivation-induced neuronal apoptosis through modulation of PI3K/Akt/Gsk3beta
      pathways.

PMID- 21735138
TI  - Do peers matter in the development of self-control? Evidence from a longitudinal
      study of youth.
AB  - According to Gottfredson and Hirschi's self-control theory, child and adolescent
      variation in self-control results primarily from variations in parental
      socialization. Although much research reveals a link between parenting and self
      control, many recent studies indicate that the etiology of self-control is more
      complex than what has been theoretically specified. In further considering this
      issue, the current study first presents a theoretical model that emphasizes the
      role that peers may play in the development of self-control, even when accounting
      for the influence of parents. Next, we empirically assess the extent to which
      peer behavior influences self-control during childhood. The data come from a
      sample of U.S. families (n=776); 48% of the subjects are male, their age was 9
      years, and non-Hispanic whites represented 84% of the sample. The analysis
      revealed that peer behavior is significantly associated with subsequent self
      control, even after accounting for differences in parental socialization, prior
      self-control, and other potential sources of spuriousness. The implications of
      the findings for theory and future research are discussed.

PMID- 21735137
TI  - Attenuation of 1-(m-chlorophenyl)-biguanide induced hippocampus-dependent memory
      impairment by a standardised extract of Bacopa monniera (BESEB CDRI-08).
AB  - Bacopa monniera is a well-known medhya-rasayana (memory enhancing and
      rejuvenating) plant in Indian traditional medical system of Ayurveda. The effect
      of a standardized extract of Bacopa monniera (BESEB CDRI-08) on serotonergic
      receptors and its influence on other neurotransmitters during hippocampal
      dependent learning was evaluated in the present study. Wistar rat pups received a
      single dose of BESEB CDRI-08 during postnatal days 15-29 showed higher latency
      during hippocampal-dependent learning accompanied with enhanced 5HT(3A) receptor
      expression, serotonin and acetylcholine levels in hippocampus. Furthermore,
      5HT(3A) receptor agonist 1-(m-chlorophenyl)-biguanide (mCPBG) impaired learning
      in the passive avoidance task followed by reduction of 5HT(3A) receptor
      expression, 5HT and ACh levels. Administration of BESEB CDRI-08 along with mCPBG
      attenuated mCPBG induced behavioral, molecular and neurochemical alterations. Our
      results suggest that BESEB CDRI-08 possibly acts on serotonergic system, which in
      turn influences the cholinergic system through 5-HT(3) receptor to improve the
      hippocampal-dependent task.

PMID- 21735139
TI  - Characteristics and factors associated with the risk of a nicotine exposed
      pregnancy: expanding the CHOICES preconception counseling model to tobacco.
AB  - The preconception counseling model tested in the CDC funded Project CHOICES
      efficacy trial to reduce the risk of an alcohol-exposed pregnancy (AEP) could be
      extended to smokers to prevent a nicotine-exposed pregnancy (NEP), when
      pharmacotherapy can be provided safely and disclosure of these risk behaviors is
      more likely. The CHOICES model, which incorporates motivational interviewing,
      encourages reduction of AEP risk by decreasing risky drinking or using effective
      contraception; in the efficacy trial, most women chose both options. We conducted
      a secondary analysis of the CHOICES epidemiologic survey data (N = 2,672)
      (Project CHOICES Research Group in Am J Prev Med 23(3), 166-173, 2002) to
      identify the prevalence of risk of NEP and the factors associated with this risk
      using logistic regression modeling procedures. Conducted in six settings with
      women at risk for AEP, the percentage of AEP was 12.5% (333/2,672) among women of
      childbearing age (18-44). A total of 464 of the 2,672 (17.4%) were at risk for
      NEP. Among women at-risk of an unplanned pregnancy (n = 1,532), the co-occurrence
      of AEP and NEP risk was more prevalent (16.3%) than AEP risk alone (5.5%) or NEP
      risk alone (14.0%). In the multivariable model, statistically significant
      correlates for NEP risk included lifetime drug use, prior alcohol/drug treatment,
      drug use in the last 6 months, being married or living with a partner, having
      multiple sexual partners in the last 6 months, physical abuse in the last year,
      and lower levels of education. These findings suggest that preconception
      counseling for NEP could be combined with a program targeting AEP.

PMID- 21735140
TI  - Trimester of maternal gestational weight gain and offspring body weight at birth
      and age five.
AB  - To investigate associations of trimester-specific GWG with fetal birth size and
      BMI at age 5 years. We examined 3,015 singleton births to women without pregnancy
      complications from the Child Health and Development Studies prospective cohort
      with measured weights during pregnancy. We used multivariable regression to
      examine the associations between total and trimester gestational weight gain
      (GWG) and birth weight for gestational age and child BMI outcomes, adjusting for
      maternal age, race/ethnicity, education, marital status, parity, pre-pregnancy
      body mass index (BMI), and smoking; paternal overweight, gestational age, and
      infant sex. We explored differences in associations by maternal BMI and infant
      sex. GWG in all trimesters was significantly and independently associated with
      birth weight with associations stronger, though not significantly, in the second
      trimester. First trimester GWG was associated with child BMI outcomes (OR for
      child overweight = 1.05; 95% CI = 1.02, 1.09). Each kg of first trimester GWG was
      significantly associated with increased child BMI z-score in women of low (beta =
      0.099; 95% CI = 0.034, 0.163) and normal (beta = 0.028; 95% CI = 0.012, 0.044),
      but not high pre-pregnancy BMI. GWG in all trimesters was associated with birth
      weight; only first trimester GWG was associated with child BMI. If replicated,
      this information could help specify recommendations for maternal GWG and
      elucidate mechanisms connecting GWG to child BMI.

PMID- 21735141
TI  - Perinatal depressive symptoms among Arab women in northern Israel.
AB  - Perinatal depression, a prevalent condition with negative consequences for the
      mother, infant and family, has been reported in many countries. This study aimed
      to assess the scope of depressive symptoms among pregnant and postnatal Israeli
      Arab women and to identify possible risk factors. Data were collected from a
      screening program at 58 Mother-Child Health Care clinics in northern Israel from
      June to December, 2009. Participants included 1,254 pregnant and 2,326 postnatal
      women. The rate of antenatal depressive symptoms, i.e., a score of >=10 on the
      Edinburgh Postnatal Depression Scale (EPDS) was 20.8%. Women attending clinics
      with primarily religious or traditional populations had lower rates antenatally
      than did those described as secular. During the postnatal period 16.3% of the
      women scored >=10 on the EPDS. The rate of postnatal depressive symptoms was
      significantly higher among women living in Moslem than Druze communities (EPDS >=
      10: 19.0% vs. 13.4%, respectively, P = 0.01). Postnatally, there were no
      significant differences according to SES cluster, community size, or religious
      orientation. The rate of antenatal and postnatal depression among Arab women in
      northern Israel was somewhat higher than that of Jewish Israeli women in the same
      region, and considerably lower than that of Arab Bedouin women in southern
      Israel. Given the differences in their life styles and circumstances, health
      policy authorities should be informed regarding the needs of these various sub
      populations.

PMID- 21735142
TI  - A previously unreported malignancy of the thyroid.
AB  - Ameloblastic fibrosarcoma or ameloblastic sarcoma is an extremely rare
      odontogenic neoplasm. We report a case of an ameloblastic fibrosarcoma arising
      from thyroid gland in a 44 year-old woman. Following total thyroidectomy, a
      histopathologic, immunohistologic, and genotypic examination revealed
      ameloblastic fibrosarcoma. The tumor was composed of odontogenic epithelium,
      resembling that of ameloblastoma, and a mesenchymal part exhibiting features of
      fibrosarcoma. To our review, our case represents the first report of ameloblastic
      fibrosarcoma of the thyroid gland. Ameloblastic fibrosarcoma may arise from
      thyroid gland.

PMID- 21735143
TI  - Preoperative serum albumin is an independent prognostic predictor of survival in
      ovarian cancer.
AB  - Ovarian cancer is associated with high mortality due to asymptomatic nature of
      the disease and advance stage at presentation. In advanced stages, it is
      associated with cachexia and ascites leading to malnutrition. Nutritional status
      of a patient with cancer has been well known to be associated with survival and
      can be assessed by level of albumin in blood. Therefore, in this study, we sought
      to determine preoperative serum albumin as prognostic predictor of survival in
      patients with ovarian cancer. Preoperative serum albumin was determined in 235
      patients undergoing surgery for ovarian cancer at Royal Derby Hospital. The
      prognostic predictive value of serum albumin, along with other prognostic markers
      was then analysed using univariate and multivariate analyses. Low serum albumin
      was associated with poor survival (P < 0.001) in patients with ovarian cancer.
      There was an inverse correlation between serum albumin levels and survival with
      lower levels having poor survival. Patients with serum albumin levels of <25 g/l
      had a median survival of 4.8 months (95% CI 0-13.1 months), whilst levels >35 g/l
      were associated with median survival of 43.2 months (95% CI 11.6-20.9). Serum
      albumin (P < 0.001) retained its significance as an independent predictor of poor
      survival on Cox's multivariate regression analysis along with Age (P < 0.001) and
      FIGO stage (P < 0.001). Serum albumin can be used as an independent prognostic
      predictor of survival in patients with ovarian cancer.

PMID- 21735144
TI  - Expression of N-myc downstream-regulated gene 1 in primary gallbladder carcinoma
      and its correlation with clinicopathological features and clinical outcome.
AB  - N-myc downstream-regulated gene 1 (NDRG1), a member of the N-myc downstream
      regulated gene family, is induced under a wide variety of stress and cell growth
      regulatory conditions. In several cancers, recent studies have shown its
      association with inhibition of tumor metastasis and suggested it to be a tumor
      suppressor gene. However, its significance in primary gallbladder carcinoma (PGC)
      has not been studied. Therefore, the aim of this study was to investigate NDRG1
      expression in PGC and its prognostic significance. We examined NDRG1 expression
      in tumor specimens from 138 patients with PGC by immunohistochemistry and
      analyzed the correlation between NDRG1 expression and clinicopathologic factors
      or survival. NDRG1 was expressed in 63.8% of PGC but not in the normal epithelium
      of the gallbladder, remarkably at the invasive front of the tumors. In addition,
      NDRG1 expression was significantly associated with high histologic grade,
      advanced pathologic T stage and clinical stage, positive nodal metastasis and
      venous/lymphatic invasion. Moreover, Kaplan-Meier curves showed that NDRG1 over
      expression was significantly related to poor overall and disease-free survival
      (both P = 0.02). Furthermore, multivariate analyses showed that NDRG1 expression
      (hazard ratio, 3.338; P = 0.02) and clinical stage (hazard ratio, 3.128; P =
      0.03) were independent risk factors for disease-free survival. Our data
      demonstrate for the first time that NDRG1 expression in PGC was significantly
      correlated with unfavorable clinicopathologic features and an independent poor
      prognostic factor for disease-free survival in patients. Taken together, our
      findings suggest that NDRG1 expression could be used as a novel prognostic factor
      for patient survival and might be a potential therapeutic target in PGC.

PMID- 21735145
TI  - Maximising the duration of disease control in metastatic renal cell carcinoma
      with targeted agents: an expert agreement.
AB  - With six targeted agents approved (sorafenib, sunitinib, temsirolimus,
      bevacizumab [+interferon], everolimus and pazopanib), many patients with
      metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However,
      the optimum sequencing approach has not been defined. A group of European experts
      reviewed available data and shared their clinical experience to compile an expert
      agreement on the sequential use of targeted agents in mRCC. To date, there are
      few prospective studies of sequential therapy. The mammalian target of rapamycin
      (mTOR) inhibitor everolimus was approved for use in patients who failed treatment
      with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors
      (VEGFR) based on the results from a Phase III placebo-controlled study; however,
      until then, the only licensed agents across the spectrum of mRCC were VEGF(R)
      inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a
      large body of evidence has accumulated regarding their use in sequence. Data show
      that sequential use of VEGF(R) inhibitors may be an effective treatment strategy
      to achieve prolonged clinical benefit. The optimal place of each targeted agent
      in the treatment sequence is still unclear, and data from large prospective
      studies are needed. The Phase III AXIS study of second-line sorafenib vs.
      axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not
      yet published; other ongoing studies include the Phase III SWITCH study of
      sorafenib-sunitinib vs. sunitinib-sorafenib (NCT00732914); the Phase III 404
      study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II
      RECORD 3 study of sunitinib-everolimus vs. everolimus-sunitinib (NCT00903175).
      Until additional data are available, consideration of patient response and
      tolerability to treatment may facilitate current decision-making regarding when
      to switch and which treatment to switch to in real-life clinical practice.

PMID- 21735146
TI  - Proteome analysis of the effects of sorafenib on human hepatocellular carcinoma
      cell line HepG2.
AB  - Sorafenib is a multi-target oral anticancer drug used as first-line treatment for
      patients with advanced human hepatocellular carcinoma (HCC). But the exact
      mechanism of sorafenib involved in HCC treatment is not clear yet. In this study,
      a comparative proteomic approach was performed to identify novel sorafenib
      related proteins in HCC. Proteomes of HepG2 cells treated with sorafenib and the
      control (without sorafenib) were obtained by two-dimensional differential gel
      electrophoresis. Comprehensive analysis of proteins was focused on total protein
      spots to filtrate the different protein spots between the two groups. The
      differentially expressed proteins were identified by peptide mass fingerprinting
      with high-performance liquid chromatography-tandem mass spectrometry. Then,
      Western blot and immunohistochemistry were used to verify the expression of some
      candidate proteins. Results indicated that 19 protein spots were differentially
      expressed with significant changes, including 6 up-regulated proteins and 13 down
      regulated proteins. It was confirmed by Western blot that expressions of Annexin
      A1 and cyclophilin A were down-regulated in sorafenib-treated HCC cell lines.
      Immunohistochemical study revealed their oncogenic role in HCC tissues. These
      observations might be novel findings leading to bring new insights into the exact
      mechanism of sorafenib and identify possible therapeutic targets.

PMID- 21735147
TI  - Familial Paget disease and SQSTM1 mutations in New Zealand.
AB  - Genetic factors play an important role in the pathogenesis of Paget disease of
      bone (PDB). SQSTM1 is the most important disease-associated gene identified to
      date. We investigated the relationship of family history, phenotype, and SQSTM1
      mutation status in New Zealand (a country with a high prevalence of PDB) in
      patients with a family history and/or a severe phenotype. We studied 61 unrelated
      subjects with familial PDB. Family history was subclassified into three groups
      according to the closeness of the relationship. We also studied a fourth group of
      19 unrelated patients defined by early onset and/or severe disease but no family
      history. The PDB phenotype was defined according to age, alkaline phosphatase
      activity, and disease extent on scintiscan at the time of diagnosis. Mutations in
      exon 8 of SQSTM1 were detected by screening of genomic DNA. Four different
      mutations were identified; the ubiquitous P392L mutation and the truncating
      mutation E396X accounted for 89% of cases. Overall 26% of patients with familial
      PBD in New Zealand had disease-associated mutations in the SQSTM1 gene. Mutations
      were most prevalent (60%) in those with a parent or sibling and at least one
      other relative affected (P < 0.002). The severity of the phenotype was
      significantly related to SQSTM1 mutation status but not the strength of the
      family history (P < 0.005). SQSTM1 mutations were found in 10.5% of patients with
      early onset and/or severe disease but no family history.

PMID- 21735148
TI  - Effect of Myracrodruon urundeuva leaf lectin on survival and digestive enzymes of
      Aedes aegypti larvae.
AB  - Aedes aegypti transmits the viruses that cause yellow and dengue fevers. Vector
      control is essential, since a vaccine for dengue has not as yet been made
      available. This work reports on the larvicidal activity of Myracrodruon urundeuva
      leaf lectin (MuLL) against A. aegypti fourth-stage larvae (L(4)). Also, the
      resistance of MuLL to digestion by L(4) gut proteases and the effects of MuLL on
      protease, trypsin-like and alpha-amylase activities from L(4) gut were evaluated
      to determine if lectin remains active in A. aegypti gut and if insect enzyme
      activities can be modulated by MuLL. MuLL promoted mortality of L(4) with LC(50)
      of 0.202 mg/ml. Haemagglutinating activity of MuLL was detected even after
      incubation for 96 h with L(4) gut preparation containing protease activity. MuLL
      affected the activity of gut enzymes, inhibiting protease and trypsin activities
      and stimulating alpha-amylase activity. The results suggest that MuLL may become
      a new biodegradable larvicidal agent for dengue control. Larvicidal activity of
      MuLL may be linked to its resistance to proteolysis by larval enzymes and
      interference in the activity of digestive larval enzymes.

PMID- 21735149
TI  - Screening of the in vitro amoebicidal activities of Pastinaca armenea (Fisch. &
      C.A.Mey.) and Inula oculus-christi (L.) on Acanthamoeba castellanii cysts and
      trophozoites.
AB  - The aim of this study is to evaluate the in vitro amoebicidal activity of the
      aqueous extracts of Pastinaca armenea and Inula oculus-christi from Turkey. In
      the presence of aqueous extracts (ranging from 1.0 to 32.0 mg/ml), numbers of the
      viable Acanthamoeba castellanii trophozoites and cysts were decreased during the
      experimental process. Both extracts showed a time- and dose-dependent amoebicidal
      action on the trophozoites and cysts. Among the extracts tested, I. oculus showed
      the strongest amoebicidal effect on the trophozoites and cysts. In the presence
      of 32.00 mg/ml extract solution in the media, no viable trophozoites were
      determined from the time of 24 h. Moreover, in the presence of 16.00 mg/ml I.
      oculus-christi extract, no viable trophozoites were detected in 72 h of the
      experiment. Effectiveness of I. oculus-christi extract was found moderate against
      the cysts. In the presence of 32.00 mg/ml extract, only 25.3% of the total cysts
      were killed effectively. In the case of P. armenea, 40.3% and 23.0% of the
      trophozoites and cysts were killed in the presence of 32.00 mg/ml extract at the
      end of the experimental process (72 h), respectively.

PMID- 21735150
TI  - Neointima-inducing inflow cannula with titanium mesh for left ventricular assist
      device.
AB  - The formation of wedge thrombus is a crucial problem in any left ventricular
      assist device (LVAD) with a left ventricle apical inflow cannula. We therefore
      developed a new titanium mesh wrapped inflow cannula expecting to induce
      autologous neointima to avoid such wedge thrombus formation. We performed animal
      experiments to evaluate the feasibility of this newly developed inflow cannula
      with titanium mesh for the induction of autologous neointima. Four calves were
      implanted with the inflow cannula as well as an EVAHEART centrifugal pump LVAD
      (Sun Medical Technology Research Corp., Nagano, Japan) for a duration of about 2
      months. The titanium mesh was enveloped with neointimal tissue grown from the
      ventricular endocardium. There was no thrombus formation in any of the blood
      pumps or around the outside of the inflow cannulas. The histological findings
      showed that the neointimal tissue consisted of a layer of endothelial cells and
      fibroblasts. The newly developed inflow cannula using a titanium mesh induces
      autologous neointima formation, avoiding wedge thrombus formation.

PMID- 21735151
TI  - Influence of pressure load on durability of pulmonic xenobioprostheses in young
      adults.
AB  - The aim of this study was to investigate the effects of pressure load (pulmonary
      arterial pressure) on the long-term durability of second-generation
      xenobioprostheses in the pulmonary position in young adults. Thirteen patients
      survived pulmonary valve replacement for pulmonary regurgitation using the second
      generation aortic porcine bioprosthesis at Sapporo Medical University School of
      Medicine between 1985 and 2009. The mean age at pulmonary valve replacement was
      40.5 years, and the mean prosthetic valve size was 25.3 mm. Two patients
      developed structural valve deterioration 6 and 9 years, respectively, after
      pulmonary valve replacement. Both prosthetic valves with structural valve
      deterioration were subjected to long-term high levels of pressure load. No valve
      structural failure was observed in the remaining 11 patients who experience low
      pressure load during a mean follow-up period of 11.9 years. The freedom from
      structural valve deterioration at 15 years was 75.8% for the overall population,
      but 100% for those with low-pressure load. Our findings suggest that the long
      term durability of pulmonary-site bioprosthetic valves in young adult patients is
      promising but that pressure load might be a risk of the limited durability of the
      valve.

PMID- 21735154
TI  - A hump-backed trend in bacterial diversity with elevation on Mount Fuji, Japan.
AB  - Little is known of how bacterial diversity in soils varies with elevation. One
      previous study found a decline with elevation, whereas another found no trend. We
      chose Mount Fuji of Japan as a geologically and topographically simple mountain
      system. Samples were taken at elevational intervals, between the base of the
      mountain at 1,000 m and its summit at 3,700 m. Polymerase chain reaction
      amplified soil DNA for the bacterial 16S gene targeting V1-V3 region was
      pyrosequenced using the 454 Roche machine, and taxonomically classified with
      reference to a bioinformatic database. There was a significant "peak" in total
      bacterial diversity at around 2,500 m above the tree line with a decline towards
      the highest elevations around 3,700 m near the summit. Individual bacterial phyla
      show distinct trends-increase, decrease, or a mid-elevational "bulge" in
      diversity. Bacterial diversity does not parallel woody plant or herbaceous plant
      diversity. We suggest that beyond the tree and vegetation line, the more extreme
      temperature fluctuations, stronger UV, lack of nutrients, and more frequent
      disturbance of the loose substrate of these slopes allows less competition and
      greater bacterial species diversity due to "lottery" recruitment. However, at the
      highest elevations, the physiological challenges are so extreme that fewer
      bacterial species are capable of surviving.

PMID- 21735153
TI  - Taxonomic and functional metagenomic profiling of the microbial community in the
      anoxic sediment of a sub-saline shallow lake (Laguna de Carrizo, Central Spain).
AB  - The phylogenetic and functional structure of the microbial community residing in
      a Ca(2+)-rich anoxic sediment of a sub-saline shallow lake (Laguna de Carrizo,
      initially operated as a gypsum (CaSO(4) * 2 H(2)O) mine) was estimated by
      analyzing the diversity of 16S rRNA amplicons and a 3.1 Mb of consensus
      metagenome sequence. The lake has about half the salinity of seawater and
      possesses an unusual relative concentration of ions, with Ca(2+) and SO (4) (2-)
      being dominant. The 16S rRNA sequences revealed a diverse community with about
      22% of the bacterial rRNAs being less than 94.5% similar to any rRNA currently
      deposited in GenBank. In addition to this, about 79% of the archaeal rRNA genes
      were mostly related to uncultured Euryarchaeota of the CCA47 group, which are
      often associated with marine and oxygen-depleted sites. Sequence analysis of
      assembled genes revealed that 23% of the open reading frames of the metagenome
      library had no hits in the database. Among annotated genes, functions related to
      (thio) sulfate and (thio) sulfonate-reduction and iron-oxidation, sulfur
      oxidation, denitrification, synthrophism, and phototrophic sulfur metabolism were
      found as predominant. Phylogenetic and biochemical analyses indicate that the
      inherent physical-chemical characteristics of this habitat coupled with
      adaptation to anthropogenic activities have resulted in a highly efficient
      community for the assimilation of polysulfides, sulfoxides, and organosulfonates
      together with nitro-, nitrile-, and cyanide-substituted compounds. We discuss
      that the relevant microbial composition and metabolic capacities at Laguna de
      Carrizo, likely developed as an adaptation to thrive in the presence of moderate
      salinity conditions and potential toxic bio-molecules, in contrast with the
      properties of previously known anoxic sediments of shallow lakes.

PMID- 21735156
TI  - Occurrence of perfluorinated compounds in water and sediment of L'Albufera
      Natural Park (Valencia, Spain).
AB  - PURPOSE: Perfluorinated compounds (PFCs) are widely distributed from
      industrialized to remote locations throughout the world. This study demonstrates
      the spatial distributions of PFCs in water and sediments from the L'Albufera
      Natural Park (Valencia, Spain). METHODS: Grab water and sediment samples were
      collected. PFCs were extracted from sediments with acidified acetonitrile by
      ultrasonication and cleaned up by solid-phase extraction (SPE) and from water by
      SPE. Determination was carried out by liquid chromatography-tandem mass
      spectrometry. RESULTS: In 100% of the samples (both water and sediments),
      perfluorooctane sulfonate (PFOS) and perfluoroctanoic acid (PFOA) were the
      predominant PFCs. Among the 12 sampling sites, PFOS concentrations in sediments
      ranged from 0.10 to 4.80 ng/g dry weight and in water from 0.94 to 58.1 ng/L.
      PFOA concentrations in sediment were from 0.004 to 1.24 ng/g and in water from
      0.99 to 120 ng/L. Other perfluorocarboxylic acids (C5, C6, C7, C9, and C10) and
      perfluorosulfonates (C4 and C10) were also identified in several locations. The
      sum of all 10 compounds (SigmaPFCs) concentration range from 0.99 to 120 ng/L in
      water and from 0.25 to 17.4 ng/g in sediments. Sediment-water distribution
      coefficients (log K (D)) were in the range 2.31-4.51 and positively correlated
      with perfluoroalkyl chain length. CONCLUSIONS: PFC concentrations in water and
      sediment were both less than those able to cause acute toxicity; low but
      detectable PFCs pollution in the L'Albufera Natural Park in Valencia was
      demonstrated. These compounds are bioaccumulative; thus, the risk associated with
      these exposures requires a deeper evaluation of long-term chronic toxicity.

PMID- 21735157
TI  - New indexes for compound prioritization and complexity quantification on
      environmental monitoring inventories.
AB  - INTRODUCTION: Lists of compounds resulting from environmental monitoring may be
      conveniently represented in a very general way using Pareto distributions, after
      ranking them on descending order according to their concentration or hazard
      quotient expressed as percentages, depending on whether the objective of the
      monitoring is focussed on mass load occurrence or risk assessment respectively.
      MATERIALS AND METHODS: Ranked distributions are characterized using appropriate
      indexes, such as h (Hirsch), well known in other disciplines like bibliometry.
      Furthermore, to such ordered distributions, simple numerical power type equations
      relating rank order and occurrence probability can be fitted, following the so
      called power or Zipf law. Both h indices and the characteristic power law
      exponents are interpreted as measures of complexity of the overall mixture. On
      the other hand, compounds included within the h index may be seen as the most
      relevant in the mixture, thus providing a reasonable indication of what is worth
      analyzing. These concepts have been applied, as case study, to the
      characterization of the pharmaceutical compounds found in the input and output
      streams of wastewater treatment plants. RESULTS AND DISCUSSION: Whereas both the
      concentration load and ecotoxicity of pharmaceuticals in WWTPs obviously decrease
      in the output of the treatment (influent > effluent, sludge), complexity
      quantified using the proposed indexes does not follow the same trend, being this
      behaviour common to the three plants examined. CONCLUSION: The joint combination
      of h compounds of the three plants studied allowed optimizing the list of
      compounds to be analyzed, which must be considered the key ones for the scenario
      under study.

PMID- 21735158
TI  - On the limits of the air pollution predictability: the case of the surface ozone
      at Athens, Greece.
AB  - PURPOSE: The aim of this study is to investigate the potential effects of
      increased urbanization in the Athens city, Greece on the intrinsic features of
      the temporal fluctuations of the surface ozone concentration (SOC). METHODS: The
      detrended fluctuation analysis was applied to the mean monthly values of SOC
      derived from ground-based observations collected at the centre of Athens basin
      during 1901-1940 and 1987-2007. RESULTS: Despite the present-day SOC doubling in
      respect to SOC historic levels, its fluctuations exhibit long-range power-law
      persistence, with similar features in both time periods. This contributes to an
      improved understanding of our predictive powers and enables better environmental
      management and more efficient decision-making processes. CONCLUSIONS: The
      extensive photochemistry enhancement observed in the Athens basin from the
      beginning of the twentieth century until the beginning of the twenty-first
      century seems not to have affected the long memory of SOC correlations. The
      strength of this memory stems from its temporal evolution and provides the limits
      of the air pollution predictability at various time scales.

PMID- 21735159
TI  - Wavelet transform-based artificial neural networks (WT-ANN) in PM10 pollution
      level estimation, based on circular variables.
AB  - INTRODUCTION: In this paper, a novel method in the estimation and prediction of
      PM(10) is introduced using wavelet transform-based artificial neural networks (WT
      ANN). DISCUSSION: First, the application of wavelet transform, selected for its
      temporal shift properties and multiresolution analysis characteristics enabling
      it to reduce disturbing perturbations in input training set data, is presented.
      Afterward, the circular statistical indices which are used in this method are
      formally introduced in order to investigate the relation between PM(10) levels
      and circular meteorological variables. Then, the results of the simulation of
      PM(10) based on WT-ANN by use of MATLAB software are discussed. The results of
      the above-mentioned simulation show an enhanced accuracy and speed in PM(10)
      estimation/prediction and a high degree of robustness compared with traditional
      ANN models.

PMID- 21735160
TI  - Abundance and diversity of Sphingomonas in Shenfu petroleum-wastewater irrigation
      zone, China.
AB  - INTRODUCTION: Members of the genus Sphingomonas have raised increasing attention
      due to their ability for polycyclic aromatic hydrocarbon (PAH) degradation and
      their ubiquity in the environment. However, few studies have revealed the
      ecological information on the abundance and diversity of Sphingomonas in the
      environment. MATERIALS AND METHODS: A primer set targeting the Sphingomonas 16S
      rRNA gene was designed. The specificity was tested with four petroleum
      contaminated soils by construction of clone libraries and further restriction
      fragment length polymorphism analysis. Subsequently, real time PCR and denaturing
      gradient gel electrophoresis (DGGE) assays were used to evaluate the abundance
      and diversity of Sphingomonas in the Shenfu irrigation zone, China. RESULTS: A
      genus-specific primer set SA/429f-933r was developed, and 90% of the sequences
      retrieved from soil clone libraries were related to Sphingomonas. Members of the
      genus Sphingomonas were detected in all soils, and significant correlation (p <
      0.05) was observed between the Sphingomonas abundance and the ratios of PAHs to
      total petroleum hydrocarbon (TPH). DGGE profiles revealed Sphingomonas population
      structures differed greatly in different sites. The Sphingomonas diversity was
      not statistically (p > 0.05) correlated with the contamination level. Some of the
      soil-derived sequences were not grouped phylogenetically with sequences of known
      Sphingomonas, indicating new members of the Sphingomonas genus might be present
      in the Shenfu irrigation zone. CONCLUSION: The newly designed Sphingomonas
      selective primers were specific and practicable for analyzing Sphingomonas
      abundance and diversity in petroleum-contaminated soils. The significant
      correlation between the abundance and the ratios of PAHs to TPH suggested an
      important role of Sphingomonas in PAH bioremediation.

PMID- 21735161
TI  - Levoglucosan and carbonaceous species in the background aerosol of coastal
      southeast China: case study on transport of biomass burning smoke from the
      Philippines.
AB  - INTRODUCTION: Levoglucosan and carbonaceous species in the background aerosol of
      coastal southeast China were measured at Jianfengling (JFL), a background
      mountain site in a National Reserve Park on Hainan Island, and at Hok Tsui (HT),
      a rural site on the southern coast of Hong Kong from April to May of 2004 during
      an intensive field study. METHODS: We integrated the information from field
      study, satellite and backward trajectory model to examine the long-range
      transport of biomass burning smoke from the Philippines and assess its impact on
      background aerosol in coastal southeast China. RESULTS AND DISCUSSION: The
      average levoglucosan concentrations were 42 and 30 ng m(-3) at JFL and HT,
      respectively, while the organic and elemental carbon concentrations were 3.1 and
      0.4 MUg C m(-3) respectively at JFL, and 4.1 and 1.3 MUg C m(-3) respectively at
      HT. Elevated levoglucosan concentrations of 85-106 ng m(-3) (250-340% extra
      loadings) at JFL and 57 ng m(-3) (170% extra loading) at HT were observed during
      transport events in which air masses originated from the Philippines. Fire hot
      spot counts and aerosol index derived from satellite data showed that the spread
      of biomass burning smoke from the Philippines resulted in large-scale dense
      aerosol clouds in the adjacent South China Sea and the western Pacific Ocean. The
      observed high ratio of two biomass-burning tracers (levoglucosan to mannosan) at
      JFL (7-36) and HT (27) indicated that the biomass smoke originating from the
      Philippines had significant contributions from open-field burning of agricultural
      residues, such as rice straw. The pollution plumes were transported to southeast
      China resulting in elevated concentrations of carbonaceous aerosol and
      levoglucosan in particular. Using a simplified receptor-based approach, biomass
      smoke aerosol was estimated to account for 16-28% of OC in the background
      atmosphere of Hainan and 4.9% of OC at the rural site of Hong Kong during these
      episode cases, indicating that biomass burning smoke generated in the Philippines
      could have a significant contribution to background ambient aerosol of southeast
      coastal China.

PMID- 21735162
TI  - Metal contamination of soils and plants associated with the glass industry in
      North Central India: prospects of phytoremediation.
AB  - INTRODUCTION: The effect of the glass industry on urban soil metal
      characterization was assessed in the area of Firozabad, India. A comprehensive
      profile of metal contamination was obtained in five zones each containing five
      specific sites. FINDINGS: Zn, Cd, and As showed a greater accumulation, whereas
      accumulation of Ni and Cu was high in limited samples. Positive correlation was
      found for the metal pairs Cu-Zn, Cu-Co, and Cu-Cr at P < 0.01. Moderate positive
      correlation was also observed between Zn-Co, Mn-Cd, Mn-As, Pb-As, and Ni-Cu at P
      < 0.05. Integrated contamination indices indicate that 60% of the sites were
      heavily contaminated while 28% were moderately contaminated. Phytoremedial
      potential of native flora (twenty herbs, three shrubs, and two grasses) was also
      assessed by analyzing their metal uptake. Individual elements displayed
      remarkably different patterns of accumulation in soils as well as in plants. Mn,
      Zn, Cu, and As were predominantly partitioned in shoots, Co and Cd in roots while
      Pb, Cr, and Ni almost equally between shoots and roots. Most plants exhibited
      capabilities in mobilizing Co, Pb, Cr, and Ni in the root zone. CONCLUSION:
      Potential phytoextractors include Datura stramonium and Chenopodium murale while
      phytostabilizers include Calotropis procera and Gnaphalium luteo-album. Poa annua
      showed potential in both categories. None of the species showed phytoremedial
      potential for Co and Ni.

PMID- 21735163
TI  - Evaluation of the biochemical components and chromatic properties of the juice of
      Vaccinium macrocarpon Aiton and Vaccinium oxycoccos L.
AB  - Benzoic acid, total anthocyanins, soluble solids, titratable acidity, and colour
      properties in juice of the American cranberry Vaccinium macrocarpon and the
      European cranberry Vaccinium oxycoccos were investigated. Berry juices of V.
      macrocarpon cultivars were distinguished by their higher total anthocyanin and
      benzoic acid amounts. These cultivars accumulated on average 43.11 mg/l of
      benzoic acid and 92.45 mg/l of total anthocyanins. The levels of benzoic acid and
      total anthocyanins in V. oxycoccos cultivars were 17.52 mg/l and 42.54 mg/l,
      respectively. The V. macrocarpon cultivars 'Franklin', 'Le Munyon', 'Searles',
      and 'Early Richard' were selected as the best according to the enhanced total
      anthocyanins and benzoic acid amounts. The separation of anthocyanins by HPLC-UV
      VIS revealed the presence of six anthocyanins, with peonidin-3-galactoside being
      the most prevalent. Galactoside together with glucoside conjugates comprised the
      largest percentage of total anthocyanins in the juices of V. macrocarpon and V.
      oxycoccos cultivars.

PMID- 21735164
TI  - Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated
      for cancer pain? A cross-sectional multicentre study.
AB  - OBJECTIVE: Opioids are recommended by the World Health Organization for moderate
      to severe cancer pain. Oxycodone is one of the most commonly used opioids and is
      metabolized in the liver by CYP3A4 and CYP2D6 enzymes. The aim of this cross
      sectional study was to assess the relationship between oxycodone
      pharmacokinetics, pharmacodynamics and the CYP2D6 genotypes "poor metaboliser"
      (PM), "extensive metaboliser" (EM) and "ultra-rapid metaboliser" (URM) in a
      cohort of patients with cancer pain. METHODS: The patients were genotyped for the
      most common CYP2D6 variants and serum concentrations of oxycodone and metabolites
      were determined. Pain was assessed using the Brief Pain Inventory (BPI). The
      EORTC QLQ-C30 was used to assess the symptoms of tiredness and nausea. Cognitive
      function was assessed by the Mini Mental State (MMS) examination. Associations
      were examined by analyses of variance (ANOVA) and covariance (ANCOVA), or ordinal
      logistic regressions with and without covariates. RESULTS: The sample consisted
      of 27 PM, 413 EM (including heterozygotes) and 10 URM. PM had lower oxymorphone
      and noroxymorphone serum concentrations and oxymorphone to oxycodone ratios than
      EM and URM. No differences between PM, EM and URM in pain intensity, nausea,
      tiredness or cognitive function was found. CONCLUSION: CYP2D6 genotypes caused
      expected differences in pharmacokinetics, but they had no pharmacodynamic
      consequence. CYP2D6 genotypes did not influence pain control, the adverse
      symptoms nausea and sedation or the risk for cognitive failure in this study of
      patients treated with oxycodone for cancer pain.

PMID- 21735165
TI  - A comparative study of the recombination pattern in three species of Platyrrhini
      monkeys (primates).
AB  - Homologous chromosomes exchange genetic information through recombination during
      meiotic synapsis, a process that increases genetic diversity and is fundamental
      to sexual reproduction. Meiotic studies in mammalian species are scarce and
      mainly focused on human and mouse. Here, the meiotic recombination events were
      determined in three species of Platyrrhini monkeys (Cebus libidinosus, Cebus
      nigritus and Alouatta caraya) by analysing the distribution of MLH1 foci at the
      stage of pachytene. Moreover, the combination of immunofluorescence and
      fluorescent in situ hybridisation has enabled us to construct recombination maps
      of primate chromosomes that are homologous to human chromosomes 13 and 21. Our
      results show that (a) the overall number of MLH1 foci varies among all three
      species, (b) the presence of heterochromatin blocks does not have a major
      influence on the distribution of MLH1 foci and (c) the distribution of crossovers
      in the homologous chromosomes to human chromosomes 13 and 21 are conserved
      between species of the same genus (C. libidinosus and C. nigritus) but are
      significantly different between Cebus and Alouatta. This heterogeneity in
      recombination behaviour among Ceboidea species may reflect differences in genetic
      diversity and genome composition.

PMID- 21735166
TI  - Chromosomal imbalances in carcinoma showing thymus-like elements (CASTLE).
AB  - Carcinoma showing thymus-like elements (CASTLE) is a rare neoplasm of the thyroid
      gland resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus
      and is thought to arise from ectopic thymic tissue within the thyroid gland or
      rudimentary branchial pouches along the thymic line. Using comparative genomic
      hybridization (CGH), chromosomal imbalances have been detected in several types
      of thymomas and thymic carcinomas. To evaluate whether there are hints of an
      underlying sequence in the pathogenesis of CASTLE analogue to those found in
      thymomas and thymic carcinomas, we evaluated four of these rare neoplasms for
      chromosomal imbalances using CGH. The most frequent gains were seen on
      chromosomal arm 1q (3/4), and losses were most frequently detected on 6p (4/4),
      6q (3/4) and 16q (3/4). These CGH data show that CASTLE is characterized by
      chromosomal imbalances similar to those found in thymomas and thymic carcinomas
      and indicate a similar sequence in tumour development.

PMID- 21735167
TI  - Primary malignant tumour of the lung with neuroendocrine and melanoma
      differentiation.

PMID- 21735168
TI  - The colorectal tumor microenvironment: the next decade.
AB  - Colorectal cancer cells establish a crosstalk with the tumor microenvironment,
      such that implantation and development of the tumor is generally favoured. CRC
      progression depends on mutations in the tumor's oncogenic pathways as well as
      metastasis suppressor genes, but is also influenced by the inflammatory
      components in the microenvironment. Inflammation results from the dietary intakes
      and is either compounded or counterbalanced by our lifestyles. Whether driven by
      intrinsic pathways or infection, inflammation produces a massive influx of
      cytokines and chemokines. Currently, in colorectal cancer, the best approach to
      counter this inflammatory wave in the microenvironment appears to be CCL2
      cytokine targeting. A fairly new avenue of discovery has identified microRNAs
      regulating colorectal cancer-mediated inflammation, and in particular the IL-6
      pro-inflammatory pathway that induces pro-apoptotic genes and HIF1alpha-elicited
      VEGF secretion. miRNAs also play a significant role in controlling metabolic
      genes such as the upregulation of the fatty acid synthase gene with the
      concomitant down-regulation of the carnitine palmitoyl transferase 1 gene. Within
      the metastatic environment, the Discoidin domain receptor-2 (DDR2) gene encodes a
      tyrosine kinase receptor for fibrillar collagen that contributes to colorectal
      cancer metastasis by increasing myofibroblasts, neoangiogenic vessels and
      proliferating cancer cells. Ongoing identification of gene signatures
      differentiating between primary tumor cells and their metastatic counterparts
      promises a wealth of new targets to be exploited for further therapeutic use
      within the next decade.

PMID- 21735169
TI  - Angiogenesis and multiple myeloma.
AB  - The bone marrow microenvironment in multiple myeloma is characterized by an
      increased microvessel density. The production of pro-angiogenic molecules is
      increased and the production of angiogenic inhibitors is suppressed, leading to
      an "angiogenic switch". Here we present an overview of the role of angiogenesis
      in multiple myeloma, the pro-angiogenic factors produced by myeloma cells and the
      microenvironment, and the mechanisms involved in the myeloma-induced angiogenic
      switch. Current data suggest that the increased bone marrow angiogenesis in
      multiple myeloma is due to the aberrant expression of angiogenic factors by
      myeloma cells, the subsequent increase in pro-angiogenic activity of normal
      plasma cells as a result of myeloma cell angiogenic activity, and the increased
      number of plasma cells overall. Hypoxia also contributes to the angiogenic
      properties of the myeloma marrow microenvironment. The transcription factor
      hypoxia-inducible factor-1alpha is overexpressed by myeloma cells and affects
      their transcriptional and angiogenic profiles. In addition, potential roles of
      the tumor suppressor gene inhibitor of growth family member 4 and homeobox B7
      have also been recently highlighted as repressors of angiogenesis and pro
      angiogenic related genes, respectively. This complex pathogenetic model of
      myeloma-induced angiogenesis suggests that several pro-angiogenic molecules and
      related genes in myeloma cells and the microenvironment are potential therapeutic
      targets.

PMID- 21735170
TI  - Mitochondrial DNA and inflammatory diseases.
AB  - Increasing experimental evidence supports a connection between inflammation and
      mitochondrial dysfunction. Both acute and chronic inflammatory diseases course
      with elevated free radicals production that may affect mitochondrial proteins,
      lipids, and mtDNA. The subsequent mitochondrial impairment produces more reactive
      oxygen species that further reduce the ATP generation, increasing the probability
      of cell death. Mitochondrial impairment in now considered a key factor in
      inflammation because (1) there are specific pathologies directly derived from
      mtDNA mutations, causing chronic inflammatory diseases such as neuromuscular and
      neurodegenerative disorders, (2) there are neurodegenerative, metabolic, and
      other inflammatory diseases in which their progression is accompanied by
      mitochondrial dysfunction, which is directly involved in the cell death.
      Recently, a direct implication of mitochondrial reactive oxygen species and,
      particularly, mtDNA in the innate immune response has been reported. Thus, the
      mitochondria should be considered targets for new therapies related to the
      treatment of acute and chronic inflammatory diseases, including the auto
      inflammatory ones.

PMID- 21735171
TI  - Artifact due to differential error when cases and controls are imputed from
      different platforms.
AB  - Including previously genotyped controls in a genome-wide association study can
      provide cost-savings, but can also create design biases. When cases and controls
      are genotyped on different platforms, the imputation needed to provide genome
      wide coverage will introduce differential measurement error and may lead to false
      positives. We compared genotype frequencies of two healthy control groups from
      the Nurses' Health Study genotyped on different platforms [Affymetrix 6.0 (n =
      1,672) and Illumina HumanHap550 (n = 1,038)]. Using standard imputation quality
      filters, we observed 9,841 single-nucleotide polymorphisms (SNPs) out of
      2,347,809 (0.4%) significant at the 5 * 10(-8) level. We explored three methods
      for controlling for this Type I error inflation. One method was to remove
      platform effects using principal components; another was to restrict to SNPs of
      highest quality imputation; and a third was to genotype some controls alongside
      cases to exclude SNPs that are statistical artifact. The first method could not
      reduce the Type I error rate; the other two could dramatically reduce the error
      rate, although both required that a portion of SNPs be excluded from analysis.
      Ideally, the biases we describe would be eliminated at the design stage, by
      genotyping sufficient numbers of cases and controls on each platform. Researchers
      using imputation to combine samples genotyped on different platforms with
      severely unbalanced case-control ratios should be aware of the potential for
      inflated Type I error rates and apply appropriate quality filters. Every SNP
      found with genome-wide significance should be validated on another platform to
      verify that its significance is not an artifact of study design.

PMID- 21735172
TI  - Identification of a new susceptibility variant for multiple sclerosis in OAS1 by
      population genetics analysis.
AB  - Contrasting results have been reported concerning the association of a splice
      site polymorphism (rs10774671) in OAS1 with multiple sclerosis (MS). We analysed
      two OAS1 regions encompassing alternatively spliced exons. While the region
      carrying the splice-site variant is neutrally evolving, a signature of long
      standing balancing selection was observed across an alternative exon 7. Analysis
      of variants in this exon identified an insertion/deletion polymorphism
      (rs11352835, A/-) that originates predicted products with distinct C termini.
      This variant is located along the major branch of the haplotype genealogy,
      suggesting that it may represent the selection target. A case/control study for
      MS indicated that rs11352835 is associated with disease susceptibility (for an
      allelic model with the deleted allele predisposing to MS, OR 1.27, 95% CI 1.072
      1.513, p = 0.010). No association was found between rs10774671 and MS. As the two
      SNPs are in linkage disequilibrium in Europeans, the previously reported
      association between rs10774671 and MS susceptibility might be driven by
      rs11352835, possibly explaining the contrasting results previously observed for
      the splice-site polymorphism. Thus, we describe a novel susceptibility variant
      for MS in OAS1 and show that population genetic analyses can be instrumental to
      the identification of selection targets and, consequently, of functional
      polymorphisms with an effect on phenotypic traits.

PMID- 21735173
TI  - Common variants for atrial fibrillation: results from genome-wide association
      studies.
AB  - Atrial fibrillation (AF) affects more than 5 million people worldwide; however,
      none of the anti-arrhythmic drugs available now are entirely optimal in terms of
      efficacy and safety. A better understanding of the molecular mechanism of AF will
      facilitate the process of finding new strategies to prevent AF. As the non
      familial AF is the major form of AF, identifying common variants for AF in these
      populations by genome-wide association studies will definitely accelerate this
      process. This review summarizes the recently identified common AF variants on
      4q25, 16q22, and 1q21 and discusses their implications for the clinic.

PMID- 21735174
TI  - Spread of X-chromosome inactivation into chromosome 15 is associated with Prader
      Willi syndrome phenotype in a boy with a t(X;15)(p21.1;q11.2) translocation.
AB  - X-chromosome inactivation (XCI) is an essential mechanism in females that
      compensates for the genome imbalance between females and males. It is known that
      XCI can spread into an autosome of patients with X;autosome translocations. The
      subject was a 5-year-old boy with Prader-Willi syndrome (PWS)-like features
      including hypotonia, hypo-genitalism, hypo-pigmentation, and developmental delay.
      G-banding, fluorescent in situ hybridization, BrdU-incorporated replication,
      human androgen receptor gene locus assay, SNP microarrays, ChIP-on-chip assay,
      bisulfite sequencing, and real-time RT-PCR were performed. Cytogenetic analyses
      revealed that the karyotype was 46,XY,der(X)t(X;15)(p21.1;q11.2),-15. In the
      derivative chromosome, the X and half of the chromosome 15 segments showed late
      replication. The X segment was maternal, and the chromosome 15 region was
      paternal, indicating its post-zygotic origin. The two chromosome 15s had a
      biparental origin. The DNA methylation level was relatively high in the region
      proximal from the breakpoint, and the level decreased toward the middle of the
      chromosome 15 region; however, scattered areas of hypermethylation were found in
      the distal region. The promoter regions of the imprinted SNRPN and the non
      imprinted OCA2 genes were completely and half methylated, respectively. However,
      no methylation was found in the adjacent imprinted gene UBE3A, which contained a
      lower density of LINE1 repeats. Our findings suggest that XCI spread into the
      paternal chromosome 15 led to the aberrant hypermethylation of SNRPN and OCA2 and
      their decreased expression, which contributes to the PWS-like features and hypo
      pigmentation of the patient. To our knowledge, this is the first chromosome-wide
      methylation study in which the DNA methylation level is demonstrated in an
      autosome subject to XCI.

PMID- 21735175
TI  - Novel intragenic duplications and mutations of CASK in patients with mental
      retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH).
AB  - The CASK gene encoding a member of the membrane-associated guanylate kinase
      protein family is highly expressed in the mammalian nervous system of both adults
      and fetuses, playing several roles in neural development and synaptic function.
      Recently, CASK aberrations caused by both mutations and deletions have been
      reported to cause severe mental retardation (MR), microcephaly and
      disproportionate pontine and cerebellar hypoplasia (MICPCH) in females. Here,
      mutations and copy numbers of CASK were examined in ten females with MR and
      MICPCH, and the following changes were detected: nonsense mutations in three
      cases, a 2-bp deletion in one case, mutations at exon-intron junctions in two
      cases, heterozygous deletions encompassing CASK in two cases and interstitial
      duplications in two cases. Except for the heterozygous deletions, each change
      including the intragenic duplications potentially caused an aberrant transcript,
      resulting in CASK null mutations. The results provide novel mutations and copy
      number aberrations of CASK, causing MR with MICPCH, and also demonstrate the
      similarity of the phenotypes of MR with MICPCH regardless of the CASK mutation.

PMID- 21735176
TI  - The control of mitochondrial succinate-dependent H2O2 production.
AB  - In brain mitochondria succinate activates H(2)O(2) release, concentration
      dependently (starting at 15 MUM), and in the presence of NAD dependent substrates
      (glutamate, pyruvate, beta-hydroxybutyrate). We report that TCA cycle metabolites
      (citrate, isocitrate, alpha-ketoglutarate, fumarate, malate) individually and
      quickly inhibit H(2)O(2) release. When they are present together at physiological
      concentration (0.2, 0.01, 0.15, 0.12, 0.2 mM respectively) they decrease H(2)O(2)
      production by over 60% at 0.1-0.2 mM succinate. The degree of inhibition depends
      on the concentration of each metabolite. Acetoacetate is a strong inhibitor of
      H(2)O(2) release, starting at 10 MUM and acting quickly. It potentiates the
      inhibition induced by TCA cycle metabolites. The action of acetoacetate is
      partially removed by beta-hydroxybutyrate. Removal is minimal at 0.1 mM
      acetoacetate, and is higher at 0.5 mM acetoacetate. We conclude that several
      inhibitors of H(2)O(2) release act jointly and concentration dependently to
      rapidly set the required level of H(2)O(2) generation at each succinate
      concentration.

PMID- 21735177
TI  - Combined pre-injection wrist and ankle MRI protocol and steroid joint injections
      in juvenile idiopathic arthritis.
AB  - Precise localization of affected compartments of the wrist and ankle in children
      with an established diagnosis of juvenile idiopathic arthritis (JIA) is
      clinically challenging. The purpose of this paper is to describe our experience
      utilizing a pre-injection MRI protocol of the wrist and ankle for localizing
      disease activity followed by fluoroscopically guided joint injections in children
      with JIA.

PMID- 21735178
TI  - Paraspinal tumoral calcinosis in a child with systemic sclerosis/myositis
      overlap.

PMID- 21735179
TI  - Hippocampal sclerosis in children younger than 2 years.
AB  - BACKGROUND: Hippocampal sclerosis (HS) is rarely considered as a diagnosis in
      children younger than 2 years. OBJECTIVE: To describe imaging features in
      conjunction with clinical information in patients with hippocampal sclerosis who
      are younger than 2 years. MATERIALS AND METHODS: We retrospectively reviewed MR
      brain imaging and clinical information in five children in whom the diagnosis of
      HS was made both clinically and by MRI prior to 2 years of age. RESULTS: Imaging
      features establishing the diagnosis of hippocampal sclerosis were bright T2
      signal and volume loss, while the internal architecture of the hippocampal
      formation was preserved in almost all children. Clinically, all children had an
      infectious trigger. CONCLUSION: It is necessary for radiologists to consider HS
      in children with certain clinical features to plan an MRI protocol that is
      appropriate for detection of hippocampal pathology.

PMID- 21735180
TI  - Internal hernias in children: spectrum of clinical and imaging findings.
AB  - BACKGROUND: Internal hernias are uncommon in children and their clinical and
      imaging findings have not been widely addressed. OBJECTIVE: To determine the
      spectrum of clinical and imaging findings of internal hernia (IH) in children and
      to highlight diagnostic features. MATERIALS AND METHODS: Review of clinical,
      imaging and surgical findings in 12 children with surgically proven IH. RESULTS:
      IH found in seven girls and five boys. Five of the children were neonates and
      seven were between ages 8-17 years. All neonates presented acutely and had
      transmesenteric internal hernias (TMIH) (four congenital, one acquired). In the
      older children, five presented with chronic symptoms and two presented with acute
      symptoms; the former had paraduodenal hernias (all congenital) and the latter had
      a congenital pericecal and an acquired TMIH. Only 2/5 neonatal TMIH could be
      appreciated on GI contrast examination. All five paraduodenal hernias were easily
      diagnosed on UGI series. CT, in two older children, depicted a paraduodenal
      hernia and the acquired TMIH. In 7/10 (70%) congenital IH, there was associated
      malrotation (in all four right paraduodenal hernias). CONCLUSION: There is a wide
      spectrum of clinical and imaging findings of IH in children. TMIH were difficult
      to appreciate on GI contrast examinations, but paraduodenal hernias were easy to
      appreciate. One must have a high index of suspicion for right paraduodenal hernia
      if UGI series shows duodenum and proximal small bowel to the right of the spine.

PMID- 21735181
TI  - UES pressure during phonation using high-resolution manometry and 24-h dual-probe
      pH-metry in patients with muscle tension dysphonia.
AB  - Muscle tension dysphonia (MTD) is the pathological condition in which excessive
      tension of the (para)laryngeal musculature leads to a disturbed voice. This study
      was developed to investigate if differences in pressure in the upper esophageal
      sphincter (UES) were present in patients with MTD in comparison with normal
      speakers. Concurrently, all patients were screened for gastroesophageal reflux
      disease (GERD) as an associated cause or aggravating factor in MTD. The study's
      design was a prospective case-control study. Fourteen patients with MTD (mean age
      = 40.2 years, range = 22-62 years) and 14 adult controls (mean age = 33.9 years,
      range = 23-58 years) were studied. A water-perfusion assembly with 22 sensors was
      positioned to record pressures during phonation. The mean values of the phonation
      pressures at the UES were measured. All patients underwent a dual-probe 24-h
      ambulatory pH impedance in order to measure the pH and the height of the refluxes
      from the lower esophageal sphincter to the hypopharynx. There were no significant
      differences in the UES pressures of patients with MTD compared to those of normal
      speakers during phonation tasks and reading. Two patients were identified with
      GERD. In these patients the refluxate reached the UES but this did not influence
      the UES pressures. We conclude that this study was not able to detect differences
      in phonation-induced UES pressures between patients with MTD and normal speakers
      using a standard water-perfusion high-resolution manometry assembly. Future
      investigation should be focused on developing probes with closely spaced sensors
      in the hypopharynx and the esophagus in order to investigate if differences in
      UES pressures in these study populations are present.

PMID- 21735182
TI  - Measurement of hyoid and laryngeal displacement in video fluoroscopic swallowing
      studies: variability, reliability, and measurement error.
AB  - Video fluoroscopy is commonly used in the study of swallowing kinematics.
      However, various procedures used in linear measurements obtained from video
      fluoroscopy may contribute to increased variability or measurement error. This
      study evaluated the influence of calibration referent and image rotation on
      measurement variability for hyoid and laryngeal displacement during swallowing.
      Inter- and intrarater reliabilities were also estimated for hyoid and laryngeal
      displacement measurements across conditions. The use of different calibration
      referents did not contribute significantly to variability in measures of hyoid
      and laryngeal displacement but image rotation affected horizontal measures for
      both structures. Inter- and intrarater reliabilities were high. Using the 95%
      confidence interval as the error index, measurement error was estimated to range
      from 2.48 to 3.06 mm. These results address procedural decisions for measuring
      hyoid and laryngeal displacement in video fluoroscopic swallowing studies.

PMID- 21735183
TI  - Trends, risk factors and pregnancy outcome in women with uterine rupture.
AB  - OBJECTIVE: This study aimed at determining trends, risk factors and pregnancy
      outcome in women with uterine rupture. METHODS: A population-based study,
      comparing all singleton deliveries with and without uterine rupture between 1988
      and 2009 was conducted. Statistical analysis was performed using a multiple
      logistic regression analysis. RESULTS: Uterine rupture occurred in 0.06% (n =
      138) of all deliveries included in the study (n = 240,189); 59% in women with a
      previous cesarean delivery (CD). A gradual increase in the rate of uterine
      rupture from 1988 (0.01%) to 2009 (0.05%) was noted. Independent risk factors for
      uterine rupture in a multivariable analysis were: previous CD (OR = 7.4, 95% CI
      5.2-10.6), preterm delivery (<37 weeks, OR = 2.5, 95% CI 1.5-4.1),
      malpresentation (OR = 3.0, 95% CI 1.9-4.5), parity (OR = 1.2, 95% CI 1.1-1.3 for
      each birth), and dystocia during the first and second stages of labor (OR = 4.1,
      95% CI 2.3-7.4 and OR = 11.2, 95% CI 6.7-18.7, respectively). Uterine rupture led
      to significant maternal morbidity and perinatal mortality. In another
      multivariable analysis, with perinatal mortality as the outcome variable uterine
      rupture was noted as an independent risk factor for perinatal mortality (adjusted
      OR = 17.7; 95% CI 10.0-31.4, P < .01). CONCLUSIONS: Uterine rupture, associated
      with previous cesarean delivery, malpresentation, and labor dystocia, is an
      independent risk factor for perinatal mortality.

PMID- 21735184
TI  - Weekly paclitaxel in heavily pretreated ovarian cancer patients: does this
      treatment still provide further advantages?
AB  - OBJECTIVE: To evaluate the disease control rate (DCR) in heavily pretreated and
      relapsed ovarian cancer patients re-challenged with a weekly paclitaxel schedule
      and to establish whether a correlation between dose intensity, progression-free
      interval (PFI) and overall survival (OS) exists. METHODS: Retrospective data were
      collected from 30 heavily pretreated metastatic ovarian cancer patients who
      received 80 mg/m(2)/week paclitaxel regimen. RESULTS: The treatment was well
      tolerated and showed a DCR in 70% of the patients, with only one case of grade 3
      hematological toxicity. One patient (3%) showed a complete response, 15 patients
      (50%) a partial response and five patients (17%) a stabilization of their
      disease. The regimen was mostly used as a fourth-line chemotherapy (range 2-7).
      The median dose intensity in responding patients was 57.5 mg/m(2)/week and in
      those with progressive disease 49.7 mg/m(2)/week. (p = 0.20). PFI and OS were
      increased in the responder patient groups with a log-rank test of 25.64 (p <
      0.001) and 15.10 (p = 0.0001), respectively. CONCLUSIONS: Weekly administration
      of paclitaxel was active and well tolerated as a salvage therapy for heavily
      pretreated ovarian cancer patients.

PMID- 21735185
TI  - Glycemic control during labor and delivery: a survey of academic centers in the
      United States.
AB  - PURPOSE: Significant controversy surrounds the management of blood glucose levels
      during labor and delivery. The American College of Obstetrics and Gynecology has
      recommended "tight" blood glucose control (<110 mg/dL). However, there is concern
      that tight control can increase the incidence of maternal hypoglycemia. Thus,
      there remains a lack of consensus regarding glycemic control during labor and
      delivery. To assess the current intrapartum glycemic management, we surveyed
      obstetrical residency programs in the United States. METHODS: Questionnaires were
      distributed via email and if there was no response within 3 weeks, they were
      mailed to obstetrics/gynecology residency program directors. RESULTS: Of the 117
      questionnaires distributed, 49 responses (41.9%) were received, but one was
      excluded, as it was incomplete. Although 85% of responders reported having a
      written protocol in place regarding intrapartum BG management, there was
      significant variation in target blood glucose levels, maintenance of those
      levels, monitoring of glucose levels, and fluid management during labor and
      delivery. CONCLUSION: The key finding of our survey is that there is significant
      variation in blood glucose management during labor and delivery. This survey
      identifies areas for improvement as well as areas for future research. Given the
      sparse obstetrical literature, properly conducted trials are necessary to assess
      all aspects of optimal intrapartum glucose management.

PMID- 21735186
TI  - Residents' training and the uncomfortable truths: a program director's
      perspective.

PMID- 21735187
TI  - Risk factors for intrapartum fetal death and trends over the years.
AB  - OBJECTIVE: To determine the time trends and risk factors for intrapartum fetal
      death (IPFD). STUDY DESIGN: A case-control study comparing pregnancies with and
      without IPFD between the years 1988 and 2008 was conducted. A multiple logistic
      regression model was used to determine the risk factors for IPFD. RESULTS: During
      the study period, 204,102 singleton births were analyzed; of these, 110 IPFD
      cases occurred. The following independent risk factors were identified: Bedouin
      ethnicity (OR = 1.85, 95% CI 1.22-2.8), malpresentations (OR = 2.76, 95% CI 1.71
      4.47), gestational age (OR = 0.72, 95% CI 0.69-0.76), polyhydramnios (OR = 3.49,
      95% CI 1.94-6.26), meconium-stained amniotic fluid (OR = 3.18, 95% CI 2.01-5.05),
      umbilical cord prolapse (OR = 6.64, 95% CI 2.79-15.78), placental abruption (OR =
      3.24, 95% CI 1.73-6.04), uterine rupture (OR = 38.59, 95% CI 10.58-140.71) and
      congenital malformations (OR = 2.41, 95% CI 1.47-3.97). A gradual decline over
      the years in the rate of IPFD was noted in the Bedouin population. No significant
      association was noted in the prevalence of IPFD during the weekends as compared
      to the week days (OR = 0.85; 95% CI 0.54-1.32; P = 0.475). CONCLUSION:
      Independent risk factors for IPFD are preterm birth, malpresentation,
      polyhydramnios, meconium-stained amniotic fluid, umbilical cord prolapse,
      placental abruption, uterine rupture, congenital malformations and Bedouin
      ethnicity. Weekends do not pose additional risk for the occurrence of IPFD.

PMID- 21735188
TI  - Prognostic factors in stage IA-IIA cervical cancer patients treated surgically:
      does the waiting time to the operation affect survival?
AB  - PURPOSE: This study aimed to identify prognostic factors in patients with stage
      IA-IIA cervical cancer who had undergone radical surgery and clarify whether the
      waiting time to the operation affected the recurrence and survival outcome.
      MATERIALS AND METHODS: We retrospectively reviewed the records of 117 patients
      who underwent surgical resection for stage IA-IIA cervical cancer. Patients were
      subdivided based on the waiting time from the initial visit to a gynecologist
      until surgery. Univariate analyses were performed to evaluate factors associated
      with recurrence-free and overall survival. RESULTS: The mean time from the first
      visit to surgery was 48 days (range 20-92). Recurrence-free and overall survival
      rates were not affected by the waiting time to the operation. On univariate
      analysis, lymph node metastasis (p = 0.003) and lymph-vascular space invasion (p
      = 0.015) were prognostic predictors of progression-free survival, while the
      waiting time to the operation was not (p = 0.106). Lymph node metastasis (p =
      0.007), lymph-vascular space invasion (p = 0.046), and the histological diagnosis
      (p = 0.027) were prognostic predictors of overall survival, but the waiting time
      to the operation was not (p = 0.653). CONCLUSIONS: The waiting time to the
      operation from the initial visit to surgical intervention does not adversely
      affect the outcome of cervical cancer within the time frames analyzed in this
      study. Furthermore, surgery allows the status of the lymph nodes and lymph
      vascular space invasion, dependent variables associated with survival, to be
      assessed accurately.

PMID- 21735189
TI  - Does mediolateral episiotomy decrease central defects of the anterior vaginal
      wall?
AB  - OBJECTIVE: This retrospective study investigates the effects of mediolateral
      episiotomy on the pelvic floor. METHODS: Premenopausal women suffering from
      urinary incontinence/genital prolapse who delivered only by vaginal route were
      enrolled into the study. History of diabetes, morbid obesity (BMI > 40 kg/m(2)),
      vacuum/forceps extraction, perineal lacerations that warranted repair during
      labor and any pelvic surgery were the exclusion criteria. Evaluation of the
      patients included pelvic organ prolapse quantification scores, presence of stress
      incontinence, urethral hypermobility, and questionnaires were obtained for
      overactive bladder and anal incontinence symptoms. These data obtained from
      patients with the history of mediolateral episiotomy were compared with those of
      patients with no episiotomy or any other pelvic injury that warranted surgical
      repair. RESULTS: Groups were identical by means of demographic data, POP-Q
      findings, signs and symptoms of the pelvic floor. However, in the MLE group,
      central defects on the anterior vaginal wall were less frequent. CONCLUSION:
      According to the results of this retrospective study, MLE seems to prevent
      central defects on the anterior vaginal wall. Prospective randomized studies are
      needed to draw a sufficient conclusion.

PMID- 21735190
TI  - Serum PLGF as a potential biomarker for predicting the onset of preeclampsia.
AB  - PURPOSE: Preeclampsia is one of the leading causes of maternal and perinatal
      morbidity and mortality. Till date despite years of research into the condition,
      predicting the onset of preeclampsia remains a problem. Placental growth factor
      is one of the many angiogenic factors, which shows significant altered levels in
      preeclampsia compared to normal pregnancy. The present study aims to analyze
      whether estimation of serum PLGF levels in late second trimester can act as a
      predictor of preeclampsia. METHODS: A total of 150 nulliparous pregnant women
      admitted in antenatal wards or attending antenatal clinic were included in the
      study. They were divided into three groups: 30 women being normotensive and 60
      each with diagnosed mild and severe preeclampsia, respectively. Serum samples
      collected from the study groups were subjected to ELISA, and serum PLGF level was
      calculated in all the samples. RESULTS: Mean serum PLGF levels were found to be
      significantly low in mild and severe preeclampsia as compared to normal
      pregnancy. Serum PLGF levels were highest at 26-28 weeks and were lowered at 28
      30 and 30-32 weeks of gestation within each of the three study groups. Cutoff
      value of serum PLGF levels for predicting mild and severe preeclampsia was
      calculated statistically from the analyzed data. CONCLUSION: Estimation of serum
      PLGF levels at 26 weeks of gestation in nulliparous pregnant women can be used as
      a screening test to identify women at risk for the development of preeclampsia
      with very high sensitivity.

PMID- 21735191
TI  - Pregnancy outcomes by mode of delivery among breech births.
AB  - OBJECTIVE: To compare maternal and neonatal outcomes of the vaginal delivery
      versus cesarean delivery for the breech presentation. METHODS: We reviewed the
      maternal and neonatal charts of all singleton breech deliveries of <1,000, 1,000
      1,500, 1,501-2,500, 2,501-4,000, and >4,000 g delivered between 2000 and 2006 at
      our institution. The study population consisted of 1,537 women with a fetus in a
      breech presentation. A group of 478 women that had delivered vaginally was
      compared with a group of 1,059 women, who had cesarean delivery, regarding
      neonatal mortality and morbidity (asphyxia, bone fractures, intraventricular
      hemorrhage, convulsions, respiratory distress syndrome, necrotizing
      enterocolitis, congenital hip dislocation), and maternal morbidity (febrile
      morbidity, anemia, wound infection). RESULTS: Neonatal complications did not
      differ between the group of women with term babies, <1,000 g babies, >1,500 g
      babies in breech presentation for women that had vaginal delivery and those that
      had cesarean delivery. On the other hand, breech presentation in preterm delivery
      between 1,000 and 1,500 g birth weight appears an independent risk factor for the
      neonatal mortality. There were fewer maternal complications in the vaginal group
      than in the cesarean group. CONCLUSION: Vaginal delivery of 1,000-1,500 g babies
      presenting as breech is associated with the increased neonatal mortality compared
      with cesarean delivery. Cesarean delivery is associated with maternal morbidity
      compared with the vaginal delivery.

PMID- 21735192
TI  - A randomized trial of ovulation induction with two different doses of Letrozole
      in women with PCOS.
AB  - OBJECTIVE: To compare the effects of either a 5 or 7.5 mg daily dose of Letrozole
      in PCOS women undergoing ovulation induction and timed intercourse. DESIGN:
      Prospective randomized trial. SETTING: Academic infertility care center.
      PATIENTS: Sixty-seven PCOS patients with infertility. INTERVENTIONS: Patients
      were randomly divided into two groups and treated with either 5 mg/day (30
      patients, group 1) or 7.5 mg/day (37 patients, group 2) Letrozole for 5 days
      starting from day 3 of the menstrual cycle. When the leading follicle reached 18
      mm in diameter, ovulation was triggered by an injection of HCG and timed
      intercourse was advised thereafter. MAIN OUTCOME MEASURES: The primary outcome
      measures were the number of follicles and days to reach mature follicle and the
      secondary endpoints were endometrial thickness, day 7 testosterone level,
      ovulation and pregnancy rates. RESULTS: The mean age, BMI, duration of
      infertility and basal hormone levels in both groups were similar. There was no
      significant difference in the endometrial thickness (7.87 +/- 1.67 vs 7.16 +/-
      2.04), the number of intermediate (0.83 +/- 0.75 vs 0.62 +/- 0.76) and mature
      follicles (1.13 +/- 1.11 vs 1.22 +/- 1.03) on days 12-14 between group 1 and 2,
      respectively. The days to reach mature follicle were similar in both groups (12.8
      +/- 1.36 vs 12.6 +/- 1.22). Also there was no significant difference in the day 7
      testosterone level and day 21 progesterone level between the two. Ovulation
      occurred in 90 and 89.2% of patients in group 1 and 2, respectively without a
      statistically significant difference. The pregnancy rate per first ovulatory
      cycle was 25.8% in group 1 and 21.2% in group 2 without significant difference.
      No OHSS was observed in either group. CONCLUSION(S): The results of this study
      did not show any advantage to the use of 7.5 mg/day over 5 mg/day dose of
      Letrozole as the first line treatment for induction of ovulation in women with
      PCOS.

PMID- 21735193
TI  - A randomized comparative study on vaginal administration of acetic acid-moistened
      versus dry misoprostol for mid-trimester pregnancy termination.
AB  - PURPOSE: Absorption and effectiveness of vaginally administered misoprostol
      tablets may vary according to the medium in which it is placed. This study was
      directed to compare the outcomes of vaginal administrations of acetic acid
      moistened misoprostol tablets with those of dry tablets for induction of second
      trimester abortion. METHODS: A randomized comparative trial where 322 women at 13
      20 weeks gestation, requiring medical abortion, were randomly assigned to vaginal
      administration of either acetic acid-moistened or dry misoprostol tablets with a
      dose schedule of 400 MUg three-hourly, up to a maximum five doses over 24 h. The
      same doses were repeated for another 24 h in nonresponders. Primary outcome
      measure was complete abortion rate at 24 and 48 h, and the secondary outcome
      measures were induction-abortion interval, failure rate and side effects. A
      difference of 15% in success rates at 24 h was used to calculate the sample size
      required with a power of 0.8 at the 5% significance level. RESULTS: No
      statistically significant differences in the complete abortion rates were
      observed at 24 h (70.95 vs. 68.71%, P = 0.675) and at 48 h (86.49 vs. 84.35%, P =
      0.604) when both groups were compared. The difference in mean induction-abortion
      interval was also statistically insignificant between the groups (12.5 +/- 1.6
      vs. 12.8 +/- 1.5 h, P = 0.97). Other outcome measures were also comparable in
      both groups. CONCLUSION: Moistening misoprostol tablets with 5% acetic acid
      before vaginal application creates no difference in outcomes when compared with
      those after the vaginal application of dry tablets for the termination of second
      trimester pregnancy.

PMID- 21735194
TI  - Distal radius fractures with diaphyseal involvement: fixation with fixed angle
      volar plate.
AB  - BACKGROUND: The purpose of this study was to evaluate the outcome of fractures of
      the distal radius with metaphyseal and diaphyseal involvement treated with fixed
      angle volar plates. MATERIALS AND METHODS: Twenty-one patients with fracture of
      the radius involving the diaphyseal, metaphyseal and epiphyseal parts were
      treated with fixed angle plate fixation through an extended volar Henry's
      approach. Circle wire loops, screws and intrafocal wire fixations were associated
      in 12 cases. Coexisting ulnar fractures were fixed with plates or K-wires in 8
      cases. All patients were prospectively followed using radiographs, physical
      examination, and DASH (Disabilities of the Arm, Shoulder and Hand) scores.
      RESULTS: All fractures except one, which needed a secondary bone graft to achieve
      consolidation, united by an average of 90 days. One case developed a radioulnar
      synostosis. Radiographs showed optimal reduction in 17 of 21 cases, with
      restoration of radial length in all cases and a neutral average ulnar variance.
      Nonanatomical reduction was associated with the worst results (P = 0.0006).
      Flexion and extension averaged 62.8 degrees  and 73.8 degrees , and pronation and
      supination 85.2 degrees  and 80.2 degrees , respectively. The average DASH scores
      were 30 points at 3 months, 14 points at 6 months, and 6.7 points at the time of
      final follow-up (at an average of 11 months). According to the Mayo wrist rating
      system, 14 patients showed excellent results, 5 showed good results, and 2 showed
      fair results. CONCLUSION: Fixed angle volar plates were demonstrated to be a safe
      and efficient treatment in these challenging fractures.

PMID- 21735195
TI  - Overexpression of the pepper antimicrobial protein CaAMP1 gene regulates the
      oxidative stress- and disease-related proteome in Arabidopsis.
AB  - Proteomics facilitates our understanding of cellular processes and network
      functions in the plant defense response during abiotic and biotic stresses. Here,
      we demonstrate that the ectopic expression of the Capsicum annuum antimicrobial
      protein CaAMP1 gene in Arabidopsis thaliana confers enhanced tolerance to methyl
      viologen (MV)-induced oxidative stress, which is accompanied by lower levels of
      lipid peroxidation. Quantitative comparative proteome analyses using two
      dimensional gel electrophoresis coupled with mass spectrometry identified some of
      the oxidative stress- and disease-related proteins that are differentially
      regulated by CaAMP1 overexpression in Arabidopsis leaves. Antioxidant- and
      defense-related proteins, such as 2-cys peroxiredoxin, L-ascorbate peroxidase,
      peroxiredoxin, glutathione S-transferase and copper homeostasis factor, were up
      regulated in the CaAMP1 transgenic leaf tissues. In contrast, GSH-dependent
      dehydroascorbate reductase and WD-40 repeat family protein were down-regulated by
      CaAMP1 overexpression. In addition, CaAMP1 overexpression enhanced resistance to
      Pseudomonas syringae pv. tomato (Pst) DC3000 infection and also H(2)O(2)
      accumulation in Arabidopsis. The identified antioxidant- and defense-related
      genes were differentially expressed during MV-induced oxidative stress and Pst
      DC3000 infection. Taken together, we conclude that CaAMP1 overexpression can
      regulate the differential expression of defense-related proteins in response to
      environmental stresses to maintain reactive oxygen species (ROS) homeostasis.

PMID- 21735196
TI  - Biochemical characterization of laccase from hairy root culture of Brassica
      juncea L. and role of redox mediators to enhance its potential for the
      decolorization of textile dyes.
AB  - In vitro transgenic hairy root cultures provide a rapid system for physiological,
      biochemical studies and screening of plants for their phytoremediation potential.
      The hairy root cultures of Brassica juncea L. showed 92% decolorization of Methyl
      orange within 4 days. Out of the different redox mediators that were used to
      achieve enhanced decolorization, 2, 2'-Azinobis, 3-ethylbenzothiazoline-6
      sulfonic acid (ABTS) was found to be the most efficient. Laccase activity of 4.5
      U mg(-1) of protein was observed in hairy root cultures of Brassica juncea L.,
      after the decolorization of Methyl orange. Intracellular laccase produced by B.
      juncea root cultures grown in MS basal medium was purified up to 2.0 fold with
      6.62 U mg(-1) specific activity using anion-exchange chromatography. Molecular
      weight of the purified laccase was estimated to be 148 kDa by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis. The purified enzyme efficiently
      oxidized ABTS which was also required for oxidation of the other tested
      substrates. The pH and temperature optimum for laccase activity were 4.0 and 40
      degrees C, respectively. The purified enzyme was stable up to 50 degrees C and
      was stable in the pH range of 4.0-6.0. Laccase activity was strongly inhibited by
      sodium azide, EDTA, dithiothreitol and L: -cysteine. The purified enzyme
      decolorized various textile dyes in the presence of ABTS as an efficient redox
      mediator. These findings contribute to a better understanding of the enzymatic
      process involved in phytoremediation of textile dyes by using hairy roots.

PMID- 21735197
TI  - Isolation and characterization of the fragrant cyclamen O-methyltransferase
      involved in flower coloration.
AB  - Anthocyanin O-methyltransferase (OMT) is one of the key enzymes for anthocyanin
      modification and flower pigmentation. We previously bred a novel red-purple
      flowered fragrant cyclamen (KMrp) from the purple-flowered fragrant cyclamen
      'Kaori-no-mai' (KM) by ion-beam irradiation. Since the major anthocyanins in KMrp
      and KM petals were delphinidin 3,5-diglucoside and malvidin 3,5-diglucoside,
      respectively, inactivation of a methylation step in the anthocyanin biosynthetic
      pathway was indicated in KMrp. We isolated and compared OMT genes expressed in KM
      and KMrp petals. RT-PCR analysis revealed that CkmOMT2 was expressed in the
      petals of KM but not in KMrp. Three additional CkmOMTs with identical sequences
      were expressed in petals of both KM and KMrp. Genomic PCR analysis revealed that
      CkmOMT2 was not amplified from the KMrp genome, indicating that ion-beam
      irradiation caused a loss of the entire CkmOMT2 region in KMrp. In vitro enzyme
      assay demonstrated that CkmOMT2 catalyzes the 3' or 3',5' O-methylation of the B
      ring of anthocyanin substrates. These results suggest that CkmOMT2 is functional
      for anthocyanin methylation, and defective expression of CkmOMT2 is responsible
      for changes in anthocyanin composition and flower coloration in KMrp.

PMID- 21735198
TI  - Rice CYP734A cytochrome P450s inactivate brassinosteroids in Arabidopsis.
AB  - Endogenous brassinosteroid concentrations are an important target for optimizing
      the growth of crop plants because these hormones influence yield and stress
      tolerance. The CYP734A subfamily of cytochrome P450 enzymes has been shown to
      inactivate brassinosteroid hormones in Arabidopsis and tomato. Rice has three
      genes for CYP734A enzymes whose expression appears to be up-regulated by
      exogenous brassinolide. The amino acids predicted to be in the active site of the
      rice enzymes vary when compared with the Arabidopsis protein sequence, suggesting
      that there could be differences in their ability to inactivate the hormone. We
      have cloned three CYP734A rice genes and expressed them in Arabidopsis to assess
      their efficacy as brassinosteroid-inactivating enzymes. We found that incorrect
      transcript splicing can complicate the expression of monocot genomic clones in a
      eudicot. However, the Arabidopsis system allowed us to characterize an atypical
      splice variant in one of the rice genes. cDNA clones produced high levels of
      expression and conferred the brassinosteroid inactivation phenotype. This study
      shows that Arabidopsis is a useful heterologous system for testing plant genes
      predicted to act in biochemical pathways that are conserved between monocots and
      eudicots.

PMID- 21735199
TI  - Defence responses in Rpv3-dependent resistance to grapevine downy mildew.
AB  - The Rpv3 locus determines the ability to operate an isolate-specific
      hypersensitive response (HR) against Plasmopara viticola in grapevines that carry
      a resistant Rpv3 (+) haplotype. Artificial infection was performed on leaf discs
      of Rpv3 (+) and Rpv3 (-) grapevines with two distinct isolates of the pathogen
      (avrRpv3 (+) and avrRpv3 (-)). The plant response, including the establishment of
      HR and changes in expression of 33 genes, was compared to the development of the
      pathogen. HR was induced exclusively in the Rpv3 (+) host upon inoculation with
      the avrRpv3 (+) isolate of the pathogen, which is assumed to use avrRpv3 (+)
      effectors that are recognised by/through the plant Rpv3 (+) gene product. The
      limitation imposed on pathogen growth was the result of inducible responses
      elicited by the Rpv3 (+)-avrRpv3 (+) interaction. This host reaction relied on
      transcriptional induction of the HR-associated gene HSR1 and salicylic acid
      induced pathogenesis-related (PR) genes PR-1 and PR-2 during the initial 24-48 h
      post-inoculation. These events had no parallel in the Rpv3 (-) host or upon
      infection with the avrRpv3 (-) isolate. The emerging model for Rpv3-mediated
      defence, which is dependent upon race-specific recognition, associated with up
      regulation of PR-1 and PR-2 genes, and enforced by localised HR-type necrosis, is
      compatible with the cascade of events initiated by the products of NB-LRR and LRR
      kinase receptor-like genes, such as those residing in the Rpv3 locus.

PMID- 21735200
TI  - Invasion by mobile aquatic consumers enhances secondary production and increases
      top-down control of lower trophic levels.
AB  - Increased biological diversity due to invasion by non-indigenous species (NIS) is
      a global phenomenon with potential effects on trophic interactions and ecosystem
      processes in the invaded habitat. We assessed the effects of resource
      availability and invasion of three non-indigenous invertebrate grazers (two
      crustaceans and a snail) on secondary production, relative dominance of NIS
      grazers and resource depletion in experimental freshwater mesocosms. The relative
      dominance of NIS grazers increased with increasing initial resource availability,
      although the effect was largest for one of the three species. The effect was due
      to the fact that all the included non-indigenous grazers were able to expand
      their populations quickly in response to resource addition. For the most
      dominating species, the increased grazer diversity due to invasion in turn
      resulted in higher production of grazer biomass and a more efficient depletion of
      the periphyton resource. The effect was largest at high initial resource
      availability, where NIS dominance was most pronounced. Our results show that an
      invasion-induced increase in species diversity can increase resource depletion
      and consequently production, but that the effect depends on identity of the
      introduced species. The results also suggest that properties of the recipient
      system, such as resource availability, can modulate ecosystem effects of NIS by
      affecting invader success and dominance.

PMID- 21735201
TI  - Local retention, dispersal and fluctuating connectivity among populations of a
      coral reef fish.
AB  - The persistence and resilience of marine populations in the face of disturbances
      is directly affected by connectivity among populations. Thus, understanding the
      magnitude and pattern of connections among populations and the temporal variation
      in these patterns is critical for the effective management and conservation of
      marine species. Despite recent advances in our understanding of marine
      connectivity, few empirical studies have directly measured the magnitude or
      pattern of connections among populations of marine fishes, and none have
      explicitly investigated temporal variation in demographic connectivity. We use
      genetic assignment tests to track the dispersal of 456 individual larval fishes
      to quantify the extent of connectivity, dispersal, self-recruitment and local
      retention within and among seven populations of a coral reef fish (Stegastes
      partitus) over a three-year period. We found that some larvae do disperse long
      distances (~200 km); however, self-recruitment was a regular phenomenon.
      Importantly, we found that dispersal distances, self-recruitment, local retention
      and the pattern of connectivity varied significantly among years. Our data
      highlight the unpredictable nature of connectivity, and underscore the need for
      more, temporally replicated, empirical measures of connectivity to inform
      management decisions.

PMID- 21735202
TI  - Simulated nitrogen deposition affects wood decomposition by cord-forming fungi.
AB  - Anthropogenic nitrogen (N) deposition affects many natural processes, including
      forest litter decomposition. Saprotrophic fungi are the only organisms capable of
      completely decomposing lignocellulosic (woody) litter in temperate ecosystems,
      and therefore the responses of fungi to N deposition are critical in
      understanding the effects of global change on the forest carbon cycle. Plant
      litter decomposition under elevated N has been intensively studied, with varying
      results. The complexity of forest floor biota and variability in litter quality
      have obscured N-elevation effects on decomposers. Field experiments often utilize
      standardized substrates and N-levels, but few studies have controlled the decay
      organisms. Decomposition of beech (Fagus sylvatica) blocks inoculated with two
      cord-forming basidiomycete fungi, Hypholoma fasciculare and Phanerochaete
      velutina, was compared experimentally under realistic levels of simulated N
      deposition at Wytham Wood, Oxfordshire, UK. Mass loss was greater with P.
      velutina than with H. fasciculare, and with N treatment than in the control.
      Decomposition was accompanied by growth of the fungal mycelium and increasing N
      concentration in the remaining wood. We attribute the N effect on wood decay to
      the response of cord-forming wood decay fungi to N availability. Previous studies
      demonstrated the capacity of these fungi to scavenge and import N to decaying
      wood via a translocating network of mycelium. This study shows that small
      increases in N availability can increase wood decomposition by these organisms.
      Dead wood is an important carbon store and habitat. The responses of wood
      decomposers to anthropogenic N deposition should be considered in models of
      forest carbon dynamics.

PMID- 21735203
TI  - Potential macro-detritivore range expansion into the subarctic stimulates litter
      decomposition: a new positive feedback mechanism to climate change?
AB  - As a result of low decomposition rates, high-latitude ecosystems store large
      amounts of carbon. Litter decomposition in these ecosystems is constrained by
      harsh abiotic conditions, but also by the absence of macro-detritivores. We have
      studied the potential effects of their climate change-driven northward range
      expansion on the decomposition of two contrasting subarctic litter types. Litter
      of Alnus incana and Betula pubescens was incubated in microcosms together with
      monocultures and all possible combinations of three functionally different macro
      detritivores (the earthworm Lumbricus rubellus, isopod Oniscus asellus, and
      millipede Julus scandinavius). Our results show that these macro-detritivores
      stimulated decomposition, especially of the high-quality A. incana litter and
      that the macro-detritivores tested differed in their decomposition-stimulating
      effects, with earthworms having the largest influence. Decomposition processes
      increased with increasing number of macro-detritivore species, and positive net
      diveristy effects occurred in several macro-detritivore treatments. However,
      after correction for macro-detritivore biomass, all interspecific differences in
      macro-detritivore effects, as well as the positive effects of species number on
      subarctic litter decomposition disappeared. The net diversity effects also
      appeared to be driven by variation in biomass, with a possible exception of net
      diversity effects in mass loss. Based on these results, we conclude that the
      expected climate change-induced range expansion of macro-detritivores into
      subarctic regions is likely to result in accelerated decomposition rates. Our
      results also indicate that the magnitude of macro-detritivore effects on
      subarctic decomposition will mainly depend on macro-detritivore biomass, rather
      than on macro-detritivore species number or identity.

PMID- 21735204
TI  - Successful percutaneous coil embolization of coronary-pulmonary, -carotid, and 
      internal mammary artery fistulas.
AB  - We herein describe a 57-year-old man with coronary-pulmonary artery fistulas that
      had abnormal connections between the left common carotid artery and the left
      internal mammary artery. The patient was treated with percutaneous coil
      embolization using antegrade (via the coronary artery) and retrograde (via the
      pulmonary artery) approaches. Coronary artery fistulas have diverse anatomical
      variations, and it is important to thoroughly evaluate the anatomy before
      beginning any mode of treatment, surgical or endovascular. In the case reported
      herein, multislice computed tomography played a pivotal role in the preprocedure
      evaluation.

PMID- 21735205
TI  - Impact of hypertension on short- and long-term prognoses in patients with ST
      elevation myocardial infarction and without previously known diabetes.
AB  - Hypertension is well established as a risk factor for the development of
      atherosclerosis. Data on the impact of hypertension in patients with ST elevation
      myocardial infarction are so far inconsistent, and are mainly related to studies
      performed in the thrombolytic era. We assessed the impact of hypertension over
      the short and long term in 560 patients with ST elevation myocardial infarction
      (STEMI) and without previously known diabetes, all of whom were submitted to
      mechanical revascularization and consecutively admitted to our Intensive Cardiac
      Care Unit. Hypertensive patients were older (p < 0.001), more frequently male
      (0.005), and they showed a reduced eGFR (p < 0.001). Smoking was more frequent in
      nonhypertensive patients (p < 0.001), while the incidence of three-vessel
      coronary artery disease was higher in hypertensive patients (p = 0.003). No
      difference in the in-hospital mortality rates for the two subgroups was detected.
      At follow-up (median 32.5 months, 25th-75th percentile 16.9-47.3 months), Kaplan
      Meier survival analysis detected no differences in mortality between hypertensive
      and nonhypertensive patients (log rank chi(2) 0.38, p = 0.538). According to our
      data, obtained from a large series of consecutive STEMI patients without
      previously known diabetes, all of whom were submitted to primary PCI, a history
      of hypertension does not affect mortality over either the short or the long term.
      Moreover, hypertensive patients showed an altered glucose response to stress, as
      indicated by higher admission glucose values, poorer in-hospital glucose control,
      and a higher incidence of acute insulin resistance (as indicated by the HOMA
      index). Hypertensive patients therefore appear to warrant careful metabolic
      management during their hospital courses.

PMID- 21735206
TI  - Use of technetium(99m)-ciprofloxacin scan in Pott's spine to assess the disease
      activity.
AB  - PURPOSE: The World Health Organisation has declared tuberculosis (TB) a global
      emergency and spinal tuberculosis is one of the most common forms. There is still
      controversy regarding optimum duration of treatment in osteoarticular
      tuberculosis due to the lack of well-defined criteria for the end point of
      treatment. Emergence of multi drug resistant tuberculosis, primarily due to use
      of poor drug regimens, further illustrates the need of newer and more effective
      diagnostic methods, particularly in developing countries. METHODS: This
      prospective clinical study to evaluate the role of technetium ((99m)Tc)
      ciprofloxacin scan as a tool to assess disease activity involved in 15 cases of
      TB spine with a mean age of 32.2 years (range 21-72). Following a clinico
      radiological diagnosis, all patients were treated with standard anti tubercular
      treatment and a scan was done at zero, three and six months of treatment with
      tracer activity being recorded and compared in sequential scans along with a
      parallel evaluation of clinical and radiological profile at regular intervals.
      RESULTS: Out of 15 cases, nine had an initially positive bone scan. Two patients
      (22%) converted to negative scans at three months, whereas the remaining seven
      (78%) turned negative at six months. The end of six months treatment was also
      accompanied by clinico-radiological resolution in all cases. CONCLUSION: In
      conclusion, technetium ((99m)Tc)-ciprofloxacin scan could be a promising tool for
      monitoring disease activity in selected cases of tuberculosis spine as an
      alternative for therapeutic drug monitoring; however, due to the small sample
      size, studies with a large number of patients might be of help in defining these
      cases in a better way.

PMID- 21735207
TI  - Mineralisation and mechanical strength of the glenoid cavity subchondral bone
      plate.
AB  - PURPOSE: Failures in total shoulder replacements are often due to aseptic
      loosening of the glenoid component; the subchondral bone plate is an important
      factor governing primary fixation of implant materials. Therefore, we
      investigated characteristic mineralisation patterns of the subchondral bone
      plate, which demonstrate long-term stress on articular surfaces, age-related
      changes, postsurgical biomechanical situations and regions of fixation. Using
      computed tomography osteo-absorptiometry (CT-OAM), these distribution patterns
      can be demonstrated in vivo. The aim of this study was to investigate the
      relationship between subchondral bone-plate mineralisation measured with CT-OAM
      and the mechanical strength measured by indentation. METHODS: A total of 32
      cadaverous glenoid cavities were evaluated by CT-OAM and indentation testing.
      Linear regression was used to compare mineralisation and strength of the
      subchondral bone plate. RESULTS: Results showed two patterns of mineralisation
      distribution. Twenty-eight cavities were related to bicentric distribution
      pattern and four showed a single maximum. The correlation coefficient between CT
      OAM density and subchondral bone-plate strength was determined to be between 0.62
      and 0.96 (P < 0.02). CONCLUSIONS: Long-term stress affects not only the
      subchondral but also the underlying cancellous bone. It therefore can be assumed
      that mineralisation patterns of the subchondral bone plate continue in cancellous
      bone. Areas of high density could serve as anchoring locations for orthopaedic
      implants in resurfacing the glenoid cavity.

PMID- 21735208
TI  - Comparison between the antero-posterior and anterior approaches for treating L5
      S1 vertebral tuberculosis.
AB  - PURPOSE: Both the antero-posterior and anterior approaches have been used for
      treating L5-S1 vertebral tuberculosis. However, no studies have compared the
      efficacy of the two methods in treating the disease. METHODS: The antero
      posterior (AP group, 14 cases) and anterior (A group, 13 cases) approaches were
      performed on L5-S1 vertebral tuberculosis cases who were followed up for average
      of 25 months. Clinical and radiographic data were obtained from and compared
      between groups. RESULTS: Average operative time, blood loss and pre-operative,
      post-operative and last follow-up of lumbo-sacral angles for groups AP and A were
      497 min vs 190 min, 980 ml vs 410 ml, 22.3 degrees  vs 20.6 degrees , 29.8
      degrees  vs 25.7 degrees  and 28.3 degrees  vs 23.6 degrees , respectively.
      Averaged visual analogue scale (VAS) scores in groups AP and A, respectively,
      were 6.5 vs 6.0 points before surgery and 3.0 vs 2.8 points after surgery. Mean
      ODI scores were 60.2 vs 63.0 points before and 30.0 vs 28.5 points after the
      operation for groups AP and A, respectively. Six cases in the AP group and five
      in the A group who exhibited neurological symptoms recovered to American Spinal
      Injury Association (ASIA) grade E. The average hospitalisations of groups AP and
      A lasted for 21 and 15 days, respectively. Bony fusion was achieved in both
      groups, with an average fusion time of five and four months, respectively.
      CONCLUSIONS: Both the antero-posterior and anterior approaches can effectively
      heal L5-S1 vertebral tuberculosis, but the average surgical time, blood loss and
      hospital stay following the anterior approach are prominently less than those
      following the antero-posterior approach.

PMID- 21735209
TI  - North African refugees, fleeing the fighting, admitted to Sicilian hospitals from
      January 1st to June 10th, 2011.

PMID- 21735210
TI  - Diodia vein chlorosis virus is a group-1 crinivirus.
AB  - Members of the family Closteroviridae have emerged as a major problem in
      agricultural crops in the past two decades. Diodia vein chlorosis virus (DVCV) is
      an understudied whitefly-transmitted closterovirus. Given the presence of the
      primary host for the virus in major agricultural production areas in the United
      States, we characterized the virus at the molecular level, demonstrating that it
      belongs in the genus Crinivirus, developed detection protocols, evaluated its
      host range among hosts known to harbor viruses closely related to DVCV, and
      confirmed transmission by a second whitefly species, Trialeurodes vaporariorum.

PMID- 21735211
TI  - Development of a real-time RT-PCR method for rapid detection of H9 avian
      influenza virus in the air.
AB  - Avian influenza virus (AIV) has caused serious epidemics all over the world.
      Notably, the low-pathogenic AIV H9N2 has been spreading widely, leading to
      enormous economic losses to the poultry industry. To rapidly monitor airborne H9
      AIVs in chicken houses, a real-time RT-PCR method was established and used to
      detect virus in air samples, and it was also compared with the traditional RT
      PCR. The results showed that the real-time RT-PCR possessed high specificity and
      sensitivity for H9 AIVs, and the sensitivity reached 100 copies/reaction, much
      higher than the traditional RT-PCR; airborne H9 AIVs were found in the six
      chicken houses by real-time RT-PCR, and their mean concentrations ranged from
      1.25*10(4) to 6.92*10(4) copies/m(3) air. Overall, the real-time PCR is a
      valuable tool for detecting airborne H9 AIVs.

PMID- 21735212
TI  - Relative reactivity of HIV-1 polyclonal plasma antibodies directed to V3 and MPER
      regions suggests immunodominance of V3 over MPER and dependence of high anti-V3
      antibody titers on virus persistence.
AB  - Antibodies to two crucial regions, the third variable loop (V3) of gp120 and the
      membrane-proximal external region (MPER) of gp41 are important for HIV-1
      neutralization. We here evaluated the relative binding of polyclonal plasma
      antibodies from 99 HIV-1-infected individuals from India to the consensus-C V3
      and MPER peptides and observed immunodominance of V3 over MPER (p < 0.0001). We
      further examined the V3- and MPER-specific antibody correlates with clinical
      parameters. Our results revealed that anti-V3 antibody titers are significantly
      lower in patients on ART compared to drug-naive individuals (p < 0.0001), most
      likely due to a decrease in plasma viral load, irrespective of their CD4 counts
      and total IgG. No such association was observed for MPER, with a similar trend in
      four follow-up patients. These findings strongly suggest that high titers of V3
      specific antibodies are dependent on persistence of virus in circulation, while
      antibodies to MPER are probably not.

PMID- 21735213
TI  - The interplay between Aracatuba virus and host signaling pathways: role of
      PI3K/Akt in viral replication.
AB  - In this study, we describe the interaction between Aracatuba virus (ARAV), a
      naturally occurring Brazilian vaccinia virus isolated from an outbreak at a dairy
      farm, and the host cell's signal transduction pathways. Even though ARAV
      infection led to phosphorylation of MAPKs MEK/ERK, JNK, and p38MAPK, genetic or
      pharmacological inhibition of these pathways had no impact on viral replication.
      We also provide evidence that ARAV stimulated the phosphorylation of Akt (PKB) at
      serine 473 (S473-P), a signaling event that is required for full activation of
      Akt during the infectious cycle. Furthermore, pharmacological inhibition of PI3K
      (LY294002) abrogated ARAV-induced Akt activation (S473-P) and affected early and
      late viral gene expression, which was followed by a decrease in virus yield (~1
      log). Taken together, our data shed some light onto the biological differences
      between ARAV and vaccinia virus strain WR (VACV-WR), which could contribute, at
      least in part, to the low-virulence phenotype displayed by ARAV. Thus, while the
      requirement for the PI3K/Akt pathway for successful ARAV replication is also
      shared with VACV-WR and cowpox virus strain BR (CPXV-BR), ARAV showed a lower
      replicative capacity, as well as a smaller plaque-size phenotype after infection
      of A31 cells when compared to VACV-WR.

PMID- 21735214
TI  - Acute short-term hyperoxia followed by mild hypoxia does not increase EPO
      production: resolving the "normobaric oxygen paradox".
AB  - Recent findings suggest that besides renal tissue hypoxia, relative decrements in
      tissue oxygenation, using a transition of the breathing mixture from hyperoxic to
      normoxic, can also stimulate erythropoietin (EPO) production. To further clarify
      the importance of the relative change in tissue oxygenation on plasma EPO
      concentration [EPO], we investigated the effect of a consecutive hyperoxic and
      hypoxic breathing intervention. Eighteen healthy male subjects were assigned to
      either IHH (N = 10) or CON (N = 8) group. The IHH group breathed pure oxygen
      (F(i)O(2) ~ 1.0) for 1 h, followed by a 1-h period of breathing a hypoxic gas
      mixture (F(i)O(2) ~ 0.15). The CON group breathed a normoxic gas mixture
      (F(i)O(2) ~ 0.21) for the same duration (2 h). Blood samples were taken just
      before, after 60 min, and immediately after the 2-h exposure period. Thereafter,
      samples were taken at 3, 5, 8, 24, 32, and 48 h after the exposure. During the
      breathing interventions, subjects remained in supine position. There were
      significant increases in absolute [EPO] within groups at 8 and 32 h in the CON
      and at 32 h only in the IHH group. No significant differences in absolute [EPO]
      were observed between groups following the intervention. Relative (?[EPO]) levels
      were significantly lower in the IHH than in the CON group, 5 and 8 h following
      exposure. The tested protocol of consecutive hyperoxic-hypoxic gas mixture
      breathing did not induce [EPO] synthesis stimulation. Moreover, the transient
      attenuation in ?[EPO] in the IHH group was most likely due to a hyperoxic
      suppression. Hence, our findings provide further evidence against the "normobaric
      O(2) paradox" theory.

PMID- 21735215
TI  - Muscle activations under varying lifting speeds and intensities during bench
      press.
AB  - During a set of resistance exercise performed until exhaustion, the relationship
      between intensity and the number of repetitions can be affected by lifting speed,
      with faster speeds producing higher numbers. The hypothesized mechanisms include
      enhanced utilization of the stretch-shortening cycle. This study investigated
      muscle activations under varying speeds and intensities during bench press using
      surface electromyography (EMG) to suggest further mechanisms for the above
      finding. Thirteen weight-trained men (21.7 +/- 3.6-year-old) performed bench
      press until fatigue under five intensities (40-80% 1RM), and four speeds (slow
      5.6-s/repetition, medium 2.8-s/repetition, fast 1.9-s/repetition, and ballistic
      maximum speed). Surface EMG was recorded from the pectoralis, deltoid, and
      triceps for root-mean-square amplitude and median frequency. EMG amplitudes were
      greater for faster and heavier conditions before fatigue. Faster conditions,
      however, produced a significant fall in amplitude during the final concentric
      phase compared to slower movements. After fatigue, EMG amplitude increased, with
      the speed effect being maintained. The intensity effect on amplitude either
      disappeared or remained similar, depending on the muscles. Median frequencies
      before fatigue were similar among speeds and intensities. The fall in frequency
      after fatigue was similar across speeds, but greater for lighter intensities. It
      was concluded that reduced muscle activation during the final concentric phase in
      faster conditions allowed a better muscle pump, explaining the increased
      repetition numbers. Fatigue levels are likely to have been similar across speeds,
      but greater for lower intensities. An incomplete rise in EMG amplitude after
      fatigue for lower intensities could imply an increased contribution of central
      fatigue or neuromuscular transmission failure.

PMID- 21735216
TI  - Fatigue after short (100-m), medium (200-m) and long (400-m) treadmill sprints.
AB  - The aim of this study was to compare the aetiology of neuromuscular fatigue
      following maximal sprints of different distances. It was hypothesized that
      increasing the distance would modify the type of peripheral and induce central
      fatigue. 11 subjects performed 100-, 200- and 400-m sprints on a motorized
      instrumented treadmill. Neuromuscular function, evaluated before (Pre), 30 s
      after (Post), and 5 and 30 min after the sprints (Post5 and Post30), consisted in
      determining maximal voluntary knee extensors torque (MVC), maximal voluntary
      activation of the knee extensors (%AL), maximal compound muscle action potential
      amplitude and duration on vastus lateralis, single twitch (Tw), and low- (Db10)
      and high-frequency torque. Compared with peak values, running speed decreased by
      8%, (P < 0.01), 20% (P < 0.001) and 39% (P < 0.001) at the end of the 100-, 200-
      and 400-m sprints, respectively. MVC was not altered following 100 and 200 m, but
      decreased by 14% (P < 0.001) after the 400 m, was still depreciated Post5 (-11%,
      P < 0.01) and went back to initial values Post30. A decrease in %AL (-6.0%, P <
      0.01) was observed Post5 for the 400 m. Tw, Db10 and low-to-high doublets ratio
      decreased Post-sprints and were not recovered Post30 after all sprints. Single
      maximal sprints of 100-400 m did not alter sarcolemmal excitability but induced
      progressive and substantial low-frequency fatigue and a slight reduction in
      neural drive with increasing sprint duration. Despite altered single or paired
      stimulations, MVC strength loss was detected only after the 400 m.

PMID- 21735217
TI  - Evidence of break-points in breathing pattern at the gas-exchange thresholds
      during incremental cycling in young, healthy subjects.
AB  - The present study investigated whether 'break-points' in breathing pattern
      correspond to the first ([Formula: see text]) and second gas-exchange thresholds
      ([Formula: see text]) during incremental cycling. We used polynomial spline
      smoothing to detect accelerations and decelerations in pulmonary gas-exchange
      data, which provided an objective means of 'break-point' detection without
      assumption of the number and shape of said 'break-points'. Twenty-eight
      recreational cyclists completed the study, with five individuals excluded from
      analyses due to low signal-to-noise ratios and/or high risk of 'pseudo-threshold'
      detection. In the remaining participants (n = 23), two separate and distinct
      accelerations in respiratory frequency (f (R)) during incremental work were
      observed, both of which demonstrated trivial biases and reasonably small +/-95%
      limits of agreement (LOA) for the [Formula: see text] (0.2 +/- 3.0 ml O(2) kg(-1)
      min(-1)) and [Formula: see text] (0.0 +/- 2.4 ml O(2) kg(-1) min(-1)),
      respectively. A plateau in tidal volume (V (T)) data near the [Formula: see text]
      was identified in only 14 individuals, and yielded the most unsatisfactory mean
      bias +/-LOA of all comparisons made (-0.4 +/- 5.3 ml O(2) kg(-1) min(-1)).
      Conversely, 18 individuals displayed V (T)-plateau in close proximity to the
      [Formula: see text] evidenced by a mean bias +/- LOA of 0.1 +/- 3.1 ml O(2) kg(
      1) min(-1). Our findings suggest that both accelerations in f (R) correspond to
      the gas-exchange thresholds, and a plateau (or decline) in V (T) at the [Formula:
      see text] is a common (but not universal) feature of the breathing pattern
      response to incremental cycling.

PMID- 21735218
TI  - Proteomic analysis of mitochondrial proteins in cardiomyocytes from rats
      subjected to intermittent hypoxia.
AB  - Intermittent hypoxia (IH) markedly enhances cardiac tolerance against
      ischemia/reperfusion injury, but its mechanism and molecular basis remain
      unclear. For exploring the expression of mitochondrial proteins induced by IH,
      two-dimensional electrophoresis and Thermo Finnigan LTQ mass spectrometer (MS)
      were applied. After comparing the protein profiles of myocardial mitochondria
      between IH and normoxic hearts, 14 protein spots were found to be altered more
      than threefold between the two groups, 11 of which were identified by Finnigan
      LTQ MS. Among these 11 proteins, 9 were involved in energy metabolism, including
      7 that were increased after IH. The latter were identified as aldehyde
      dehydrogenase, methylmalonate-semialdehyde dehydrogenase, ATP synthase beta
      chain, mitochondrial aconitase, malate dehydrogenase, electron transfer
      flavoprotein alpha subunit and sirtuin 5. Two other proteins, ubiquinol
      cytochrome C reductase iron-sulfur subunit and aspartate aminotransferase, were
      decreased after IH. Biochemical tests for energy metabolism in mitochondria
      supported the proteomic results. IH exposure also increased the expression of a
      molecular chaperone-heat shock protein 60 and an antioxidant protein,
      peroxiredoxin 5. These findings will provide clues for understanding the
      mechanism of IH-induced cardiac protection and may lead to the development of
      interventional strategies designed to utilize the advantages of IH clinically.

PMID- 21735219
TI  - Peripheral markers of central fatigue in trained and untrained during
      uncompensable heat stress.
AB  - The development of fatigue is more pronounced in the heat than thermoneutral
      environments; however, it is unclear whether biomarkers of central fatigue are
      consistent with the higher core temperature (T (c)) tolerated by endurance
      trained (TR) versus untrained (UT) during exertional heat stress (EHS). The
      purpose of this study was to examine the indicators of central fatigue during EHS
      in TR versus UT. Twelve TR and 11 UT males (mean +/- SE [Formula: see text] = 70
      +/- 2 and 50 +/- 1 mL kg LBM(-1) min(-1), respectively) walked on a treadmill to
      exhaustion (EXH) in 40 degrees C (dry) wearing protective clothing. Venous blood
      was obtained at PRE and 0.5 degrees C T (c) increments from 38 to 40 degrees
      C/EXH. Free tryptophan (f-TRP) decreased dramatically at 39.5 degrees C for the
      TR. Branch chain amino acids decreased with T (c) and were greater for UT than TR
      at EXH. Tyrosine and phenylalanine remained unchanged. Serum S100beta was
      undetectable (<5 pg mL(-1)). Albumin was greater for the UT from PRE to 39.0
      degrees C and at EXH. Prolactin (PRL) responded to relative thermal strain with
      similar EXH values despite higher T (c) tolerated for TR (39.7 +/- 0.09 degrees
      C) than UT (39.0 +/- 0.09 degrees C). The high EXH PRL values for both groups
      support its use as a biomarker of the serotonin and dopamine interplay within the
      brain during the development of central fatigue.

PMID- 21735221
TI  - Physiological and molecular endocrine changes in maturing wild sockeye salmon,
      Oncorhynchus nerka, during ocean and river migration.
AB  - Maturing adult sockeye salmon Oncorhynchus nerka were intercepted while migrating
      in the ocean and upstream in freshwater over a combined distance of more than
      1,300 km to determine physiological and endocrine changes associated with
      ionoregulation. Sockeye migrating through seawater and freshwater showed
      consistent declines in gill Na+/K+ -ATPase (NKA) activity, plasma osmolality and
      plasma chloride concentration. In contrast, plasma sodium concentration became
      elevated in seawater as fish approached the river mouth and was then restored
      after sockeye entered the river. Accompanying the movement from seawater to
      freshwater was a significant increase in mRNA for the NKA alpha1a subunit in the
      gill, with little change in the alpha1b subunit. Potential endocrine signals
      stimulating the physiological changes during migration were assessed by measuring
      plasma cortisol and prolactin (Prl) concentrations and quantifying mRNA extracted
      from the gill for glucocorticoid receptors 1 and 2 (GR1 and GR2),
      mineralocorticoid receptor (MR), growth hormone 1 receptor (GH1R), and prolactin
      receptor (PrlR). Plasma cortisol and prolactin concentrations were high in
      seawater suggesting a preparatory endocrine signal before freshwater entry.
      Generally, the mRNA expression for GR1, GR2 and MR declined during migration,
      most notably after fish entered freshwater. In contrast, PrlR mRNA increased
      throughout migration, particularly as sockeye approached the spawning grounds. A
      highly significant association existed between gill PrlR mRNA and gill NKA
      alpha1a mRNA. GH1R mRNA also increased significantly, but only after sockeye had
      migrated beyond tidal influence in the river and then again just before the fish
      reached the spawning grounds. These findings suggest that cortisol and prolactin
      stimulate ionoregulation in the gill as sockeye salmon adapt to freshwater.

PMID- 21735222
TI  - D-Ser-containing humanin shows promotion of fibril formation.
AB  - Humanin (HN), a peptide of 24 amino acid residues, suppresses the neuronal cell
      death that is induced by the gene products of Alzheimer's disease. HN contains
      two Ser residues at positions 7 and 14. Because the proportion of D-Ser
      isomerized from L-Ser in proteins appears to increase as cellular organs age, we
      explored the structural effects of the isomerization of each Ser residue in HN.
      By using a thioflavin-T assay to detect fibril formation, we found that an HN
      derivative that contained two isomerized D-Ser residues had a greater tendency to
      form fibrils than did wild-type HN or HNs containing single D-Ser residues. A
      previous report showed that HN containing two D-Ser residues exerts
      neuroprotective activity. Our data, therefore, suggest that the fibril formation
      by HN that contains two D-Ser residues may promote HN neuroprotective activity.

PMID- 21735220
TI  - Osmoregulation and epithelial water transport: lessons from the intestine of
      marine teleost fish.
AB  - For teleost fish living in seawater, drinking the surrounding medium is necessary
      to avoid dehydration. This is a key component of their osmoregulatory strategy
      presenting the challenge of excreting excess salts while achieving a net
      retention of water. The intestine has an established role in osmoregulation, and
      its ability to effectively absorb fluid is crucial to compensating for water
      losses to the hyperosmotic environment. Despite this, the potential for the
      teleost intestine to serve as a comparative model for detailed, integrative
      experimental studies on epithelial water transport has so far gone largely
      untapped. The following review aims to present an assessment of the teleost
      intestine as a fluid-transporting epithelium. Beginning with a brief overview of
      marine teleost osmoregulation, emphasis shifts to the processing of ingested
      seawater by the gastrointestinal tract and the characteristics of intestinal ion
      and fluid transport. Particular attention is given to acid-base transfers by the
      intestine, specifically bicarbonate secretion, which creates the distinctly
      alkaline gut fluids responsible for the formation of solid calcium carbonate
      precipitates. The respective contributions of these unique features to intestinal
      fluid absorption, alongside other recognised ion transport processes, are then
      subsequently considered within the wider context of the classic physiological
      problem of epithelial water transport.

PMID- 21735223
TI  - From optics to attention: visual perception in barn owls.
AB  - Barn owls are nocturnal predators which have evolved specific sensory and
      morphological adaptations to a life in dim light. Here, some of the most
      fundamental properties of spatial vision in barn owls are reviewed. The eye with
      its tubular shape is rigidly integrated in the skull so that eye movements are
      very much restricted. The eyes are oriented frontally, allowing for a large
      binocular overlap. Accommodation, but not pupil dilation, is coupled between the
      two eyes. The retina is rod dominated and lacks a visible fovea. Retinal ganglion
      cells form a marked region of highest density that extends to a horizontally
      oriented visual streak. Behavioural visual acuity and contrast sensitivity are
      poor, although the optical quality of the ocular media is excellent. A low f
      number allows high image quality at low light levels. Vernier acuity was found to
      be a hyperacute percept. Owls have global stereopsis with hyperacute stereo
      acuity thresholds. Neurons of the visual Wulst are sensitive to binocular
      disparities. Orientation based saliency was demonstrated in a visual-search
      experiment, and higher cognitive abilities were shown when the owl's were able to
      use illusory contours for object discrimination.

PMID- 21735224
TI  - Body condition, hormonal correlates and consequences for survival in common tern
      chicks.
AB  - Although sibling competition in avian species has been extensively studied, the
      proximate mechanisms remain largely unknown. Recent research proposed that
      steroid hormones, in particular testosterone (T) and corticosterone (CORT), might
      play a role either in promoting competitive behavioral displays or in response to
      chronic nutritional stress accompanied by a sustained competitive situation.
      Here, we examine body condition, endogenous T levels and fecal glucocorticoid
      metabolites (FGM) as non-invasive measures of CORT in sibling broods of wild
      common tern chicks (Sterna hirundo) during three post-natal developmental stages.
      In this species, distinct within-brood size asymmetries are imposed by an
      asynchronous hatching interval, and sexes show slightly different growth
      patterns. First-hatched (a-)chicks were in better condition than their later
      hatched sibling (b-chick). FGM levels inversely covaried with condition and were
      elevated at the end of pre-fledging development. T levels of a- and b-chicks
      changed with age, although the direction of the changes differed, with b-chicks
      eventually having higher levels than their older siblings. Survival to fledging
      was not associated with FGM but with T levels, which tended to be higher in
      surviving chicks. Our results are discussed with regard to how plasticity in
      steroid hormones could be involved in mediating sibling competition in common
      terns.

PMID- 21735225
TI  - Responses of round goby (Neogobius melanostomus) olfactory epithelium to steroids
      released by reproductive males.
AB  - The wild perciform teleost Neogobius melanostomus (the round goby) originated
      from the Ponto-Caspian region and is now a highly successful invasive species in
      the Laurentian Great Lakes. Males may attract females into their nests for
      spawning by releasing reproductive pheromones, and it has been previously shown
      that reproductive males synthesize and release the 5beta-reduced and 3alpha
      hydroxyl steroids 3alpha-hydroxy-5beta-androstane-11,17-dione (11-oxo
      etiocholanolone; 11-O-ETIO) and 3alpha-hydroxy-5beta-androstane-11,17-dione 3
      sulfate (11-oxo-etiocholanolone-3-sulfate; 11-O-ETIO-3-s) and 3alpha,17beta
      dihydroxy-5beta-androstan-11-one 17-sulfate. In this study, we investigated
      properties of these released steroids by recording field potential responses from
      the olfactory epithelium (electro-olfactogram, EOG). The steroid 3alpha,17beta
      dihydroxy-5beta-androstan-11-one 17-sulfate did not elicit olfactory responses
      while both 11-O-ETIO and 11-O-ETIO-3-s stimulated olfactory field potentials in
      the round goby, but not in the goldfish. Cross-adaptation analysis demonstrated
      that round gobies discriminated between11-O-ETIO and 11-O-ETIO-3-s (as well as
      etiocholanolone, ETIO) at the sensory level. Second messenger cascades depending
      on both cAMP and IP(3) were inferred for steroids from pharmacological inhibition
      studies, while the canonical teleost odors taurocholic acid (a bile acid) and L: 
      alanine (an amino acid) used only cAMP and IP(3), respectively. The round goby
      presents itself as an excellent species for the study of olfactory function of
      fish in the wild, given its possible use of these released steroids as
      pheromones.

PMID- 21735226
TI  - Recognition of host proteins by Helicobacter cysteine-rich protein C.
AB  - Tetratricopeptide- and sel1-like repeat (SLR) proteins modulate various cellular
      activities, ranging from transcription regulation to cell-fate control.
      Helicobacter cysteine-rich proteins (Hcp) consist of several SLRs that are cross
      linked by disulfide bridges and have been implicated in host/pathogen
      interactions. Using pull-down proteomics, several human proteins including Nek9,
      Hsp90, and Hsc71 have been identified as putative human interaction partners for
      HcpC. The interaction between the NimA-like protein kinase Nek9 and HcpC has been
      validated by ELISA and surface plasmon resonance. Recombinant Nek9 is recognized
      by HcpC with a dissociation constant in the lower micromolar range. This
      interaction is formed either directly between Nek9 and HcpC or via the formation
      of a complex with Hsc71. The HcpC homologue HcpA possesses no affinity for Nek9,
      suggesting that the reported interaction is rather specific for HcpC. These
      results are consistent with previous observations where Nek9 was targeted upon
      bacterial or viral invasion. However, further experiments will be required to
      show that the reported interactions also occur in vivo.

PMID- 21735227
TI  - An unusual cause of anal pain following ileal pouch-anal anastomosis.
AB  - Ileal pouch-anal anastomosis (IPAA) is a safe and effective operation in properly
      selected patients, but a variety of potential complications can occur. We present
      a case of a 56-year-old female who underwent a double-stapled IPAA for refractory
      ulcerative colitis and postoperatively developed unrelenting, severe anal pain
      requiring daily narcotics. Examination under anesthesia revealed that her pain
      was a result of staples from the anastomosis that had migrated into the highly
      sensitive anoderm below the dentate line. Removal of these staples led to
      resolution of her symptoms.

PMID- 21735228
TI  - Genetic analysis of MA4079, an aldehyde dehydrogenase homolog, in Methanosarcina
      acetivorans.
AB  - When Methanosarcina acetivorans grows on carbon monoxide (CO), it synthesizes
      high levels of a protein, MA4079, homologous to aldehyde dehydrogenases. To
      investigate the role of MA4079 in M. acetivorans, mutants lacking the encoding
      gene were generated and phenotypically analyzed. Loss of MA4079 had no effect on
      methylotrophic growth but led to complete abrogation of methylotrophic growth in
      the presence of even small amounts of CO, which indicated the mutant's inability
      to acclimate to the presence of this toxic gas. Prolonged incubation with CO
      allowed the isolation of a strain in which the effect of MA4079 deletion is
      suppressed. The strain, designated Mu3, tolerated the presence of high CO partial
      pressures even better than the wild type. Immunological analysis using antisera
      against MA4079 suggested that it is not abundant in M. acetivorans. Comparison of
      proteins differentially abundant in Mu3 and the wild type revealed an elevated
      level of methyl-coenzyme M reductase and a decreased level of one isoform of
      carbon monoxide dehydrogenase/acetyl-coenzyme A synthase, which suggests that
      pleiotropic mutation(s) compensating for the loss of MA4079 affected catabolism.
      The data presented point toward a role of MA4079 to enable M. acetivorans to
      properly acclimate to CO.

PMID- 21735229
TI  - Use of qPCR for the study of hepatotoxic cyanobacteria population dynamics.
AB  - Toxic cyanobacteria blooms are increasingly frequent and object of greater
      concern due to its ecological and health impacts. One important lack in the toxic
      cyanobacteria research field is to understand which parameters influence most and
      how they operate to regulate the overall levels of cyanotoxins in a body of
      water. MC concentration is believed to be influenced by changes in several
      seasonal environmental factors that influence the succession of toxic
      cyanobacteria. In the last years, qPCR (quantitative polymerase chain reaction)
      has been applied to determine the seasonal and temporal shifts in the proportions
      of MC-producing and non-MC-producing subpopulations by quantifying both mcy
      genotypes and total population numbers. We discuss the most prominent and recent
      studies using qPCR to address hepatotoxic cyanobacteria population dynamics and
      evaluate how they helped understanding the factors promoting the growth of toxic
      strains in situ and the succession of hepatotoxin-producing genera in natural
      populations.

PMID- 21735230
TI  - Comparative analysis of phase I and II enzyme activities in 5 hepatic cell lines
      identifies Huh-7 and HCC-T cells with the highest potential to study drug
      metabolism.
AB  - Primary human hepatocytes (hHeps) are still gold standard to perform human drug
      metabolism studies, but their availability is limited by donor organ scarcity.
      Therefore, hepatoma cell lines are widely used as alternatives, although their
      phases I and II drug-metabolizing activities are substantially lower compared
      with hHeps. The major advantage of these cell lines is immediate availability,
      standardized culture conditions and unlimited life span. Therefore, the aim of
      this study was to investigate the drug-metabolizing profile of five human
      hepatoma cell lines (HepG2, Hep3B, HCC-T, HCC-M and Huh-7) over a culture period
      of 10 passages. Fluorescent-based assays for seven different cytochrome P450
      (CYP) isoforms and seven different phase II enzymes were performed and compared
      with enzymatic activities of hHeps. CYP activities were much lower in the cell
      lines (5-15% of hHeps), whereas phase II enzyme activities that are involved in
      buffering oxidative stress (e.g., Glutathione-S-transferase) reached levels
      comparable with hHeps. Furthermore, phases I and II enzyme activities in hepatoma
      cell lines vary strongly during culture time. Interestingly, the most constant
      results were obtained with Huh-7 cells. Huh-7 cells as well as HCC-T cells
      exhibited a drug-metabolizing profile closest to hHeps between passages two and
      four. Toxicity studies with Diclofenac, Paracetamol and Verapamil in both cell
      lines show dose-response characteristics and EC(50) values similar to hHeps.
      Therefore, we propose that due to the more consistent results throughout the
      passages, Huh-7 could be an alternative system to the limitedly available hHeps
      and frequently used HepG2 cell line in the study of drug metabolism.

PMID- 21735231
TI  - Threshold of toxicological concern values for non-genotoxic effects in industrial
      chemicals: re-evaluation of the Cramer classification.
AB  - The TTC concept employs available data from animal testing to derive a
      distribution of NOAELs. Taking a probabilistic view, the 5th percentile of the
      distribution is taken as a threshold value for toxicity. In this paper, we use
      824 NOAELs from repeated dose toxicity studies of industrial chemicals to re
      evaluate the currently employed TTC values, which have been derived for
      substances grouped according to the Cramer scheme (Cramer et al. in Food Cosm
      Toxicol 16:255-276, 1978) by Munro et al. (Food Chem Toxicol 34:829-867, 1996)
      and refined by Kroes and Kozianowski (Toxicol Lett 127:43-46, 2002), Kroes et al.
      2000. In our data set, consisting of 756 NOAELs from 28-day repeated dose testing
      and 57 NOAELs from 90-days repeated dose testing, the experimental NOAEL had to
      be extrapolated to chronic TTC using regulatory accepted extrapolation factors.
      The TTC values derived from our data set were higher than the currently used TTC
      values confirming the safety of the latter. We analysed the prediction of the
      Cramer classification by comparing the classification by this tool with the
      guidance values for classification according to the Globally Harmonised System of
      classification and labelling of the United Nations (GHS). Nearly 90% of the
      chemicals were in Cramer class 3 and assumed as highly toxic compared to 22%
      according to the GHS. The Cramer classification does underestimate the toxicity
      of chemicals only in 4.6% of the cases. Hence, from a regulatory perspective, the
      Cramer classification scheme might be applied as it overestimates hazard of a
      chemical.

PMID- 21735232
TI  - ZmMKK4 regulates osmotic stress through reactive oxygen species scavenging in
      transgenic tobacco.
AB  - Mitogen-activated protein kinase kinase (MAPKKs) are important components of MAPK
      cascades, which are universal signal transduction modules and play important role
      in regulating both plant development and biotic or abiotic stress responses. In
      this study, we identified the group C MAPKK gene, ZmMKK4, in maize (Zea mays L.).
      Overexpression of ZmMKK4 in tobacco enhanced tolerance to osmotic stress by
      increased proline content and antioxidant enzyme (POD) activities compared with
      wild-type plants. RT-PCR revealed that one peroxidase (POX) gene, NtPOX1, was
      higher in ZmMKK4-overexpressing plants than in the wild-type plants. In addition,
      the accumulation of reactive oxygen species (ROS) in ZmMKK4-overexpressing plants
      is much less than that of wild-type plants. These results suggest that ZmMKK4 may
      be involved in ROS signaling. Taken together, these results indicate that ZmMKK4
      is a positive regulator of osmotic stress by regulating scavenging of ROS in
      plants.

PMID- 21735233
TI  - Identification, isolation and expression analysis of auxin response factor (ARF)
      genes in Solanum lycopersicum.
AB  - Auxin response factors (ARFs) encode transcriptional factors that bind
      specifically to the TGTCTC-containing auxin response elements found in the
      promoters of primary/early auxin response genes that regulate plant development.
      In this study, investigation of the tomato genome revealed 21 putative functional
      ARF genes (SlARFs), a number comparable to that found in Arabidopsis (23) and
      rice (25). The full cDNA sequences of 15 novel SlARFs were isolated and
      delineated by sequencing of PCR products. A comprehensive genome-wide analysis of
      this gene family is presented, including the gene structures, chromosome
      locations, phylogeny, and conserved motifs. In addition, a comparative analysis
      between ARF family genes in tomato and maize was performed. A phylogenetic tree
      generated from alignments of the full-length protein sequences of 21 OsARFs, 23
      AtARFs, 31 ZmARFs, and 21 SlARFs revealed that these ARFs were clustered into
      four major groups. However, we could not find homologous genes in rice, maize, or
      tomato with AtARF12-15 and AtARF20-23. The expression patterns of tomato ARF
      genes were analyzed by quantitative real-time PCR. Our comparative analysis will
      help to define possible functions for many of these newly isolated ARF-family
      genes in plant development.

PMID- 21735234
TI  - QTL alleles for improved fiber quality from a wild Hawaiian cotton, Gossypium
      tomentosum.
AB  - Seventeen backcross-self families from crosses between two Gossypium hirsutum
      recurrent parent lines (CA3084, CA3093) and G. tomentosum were used to identify
      quantitative trait loci (QTLs) controlling fiber quality traits. A total of 28
      QTLs for fiber quality traits were identified (P < 0.001), including four for
      fiber elongation, eight for fiber fineness, four for fiber length, four for fiber
      strength, six for fiber uniformity, one for boll weight, and one for boll number.
      Three statistically significant marker-trait associations for lint yield were
      found in a single environment, but need further validation. Two-way analysis of
      variance revealed one locus with significant genotype * family interaction (P <
      0.001) for fiber strength and a second locus with significant genotype *
      environment interaction (P < 0.001) in the CA3084 background, and two loci with
      significant genotype * background interaction (P < 0.001) for the 28 common
      markers segregating in both of the two recurrent backgrounds. Co-location of many
      QTLs for fiber quality traits partially explained correlations among these
      traits. Some G. tomentosum alleles were associated with multiple favorable
      effects, offering the possibility of rapid genetic gain by introgression. Many G.
      tomentosum alleles were recalcitrant to homozygosity, suggesting that they might
      be most effectively deployed in hybrid cottons. DNA markers linked to G.
      tomentosum QTLs identified in the present study promise to assist breeders in
      transferring and maintaining valuable traits from this exotic source during
      Upland cotton cultivar development. This study also adds further evidence to
      prior studies indicating that the majority of genetic variation associated with
      fiber quality in tetraploid cotton traces to the D-subgenome from a diploid
      ancestor that does not produce spinnable fiber.

PMID- 21735235
TI  - Fine genetic mapping of cp: a recessive gene for compact (dwarf) plant
      architecture in cucumber, Cucumis sativus L.
AB  - The compact (dwarf) plant architecture is an important trait in cucumber (Cucumis
      sativus L.) breeding that has the potential to be used in once-over mechanical
      harvest of cucumber production. Compact growth habit is controlled by a simply
      inherited recessive gene cp. With 150 F(2:3) families derived from two inbred
      cucumber lines, PI 308915 (compact vining) and PI 249561 (regular vining), we
      conducted genome-wide molecular mapping with microsatellite (simple sequence
      repeat, SSR) markers. A framework genetic map was constructed consisting of 187
      SSR loci in seven linkage groups (chromosomes) covering 527.5 cM. Linkage
      analysis placed cp at the distal half of the long arm of cucumber Chromosome 4.
      Molecular markers cosegregating with the cp locus were identified through whole
      genome scaffold-based chromosome walking. Fine genetic mapping with 1,269 F(2)
      plants delimited the cp locus to a 220 kb genomic DNA region. Annotation and
      function prediction of genes in this region identified a homolog of the cytokinin
      oxidase (CKX) gene, which may be a potential candidate of compact gene. Alignment
      of the CKX gene homologs from both parental lines revealed a 3-bp deletion in the
      first exon of PI 308915, which can serve as a marker for marker-assisted
      selection of the compact phenotype. This work also provides a solid foundation
      for map-based cloning of the compact gene and understanding the molecular
      mechanisms of the dwarfing in cucumber.

PMID- 21735236
TI  - The panorama of physiological responses and gene expression of whole plant of
      maize inbred line YQ7-96 at the three-leaf stage under water deficit and re
      watering.
AB  - Changes in water potential, growth elongation, photosynthesis of three-leaf-old
      seedlings of maize inbred line YQ7-96 under water deficit (WD) for 0.5, 1 and 2 h
      and re-watering (RW) for 24 h were characterized. Gene expression was analyzed
      using cDNA microarray covering 11,855 maize unigenes. As for whole maize plant,
      the expression of WD-regulated genes was characterized by up-regulation. The
      expression of WD-regulated genes was categorized into eight different patterns,
      respectively, in leaves and roots. Newly found and WD-affected cellular processes
      were metabolic process, amino acid and derivative metabolic process and cell
      death. A great number of the analyzed genes were found to be regulated
      specifically by RW and commonly by both WD and RW, respectively, in leaves. It is
      therefore concluded that (1) whole maize plant tolerance to WD, as well as growth
      recovery from WD, depends at least in part on transcriptional coordination
      between leaves and roots; (2) WD exerts effects on the maize, especially on basal
      metabolism; (3) WD could probably affect CO(2) uptake and partitioning, and
      transport of fixed carbons; (4) WD could likely influence nuclear activity and
      genome stability; and (5) maize growth recovery from WD is likely involved in
      some specific signaling pathways related to RW-specific responsive genes.

PMID- 21735237
TI  - Synchronous bilateral neuroendocrine ductal carcinoma in situ.
AB  - Neuroendocrine ductal carcinoma in situ (NE-DCIS) is a breast malignancy that has
      characteristic clinicopathological features and can, therefore, be regarded as a
      distinct variant of DCIS. The patient was a 54-year-old premenopausal woman with
      hemorrhagic nipple discharge in her left breast. Magnetic resonance imaging and
      ultrasound (US) images of the left breast showed mass-like lesions, while
      concurrent images of the right breast showed non-mass-like lesions. These
      findings suggested the presence of both benign and malignant tumors. Pathological
      findings from US-guided core-needle biopsy of the left mass were highly
      suspicious of a malignant tumor. Excisional biopsy of both breasts was performed.
      We could define the diagnosis of breast cancer by the second opinion on
      pathological diagnosis. The tumor cells showed histological characteristics of NE
      DCIS. Bilateral breast lesions had histopathological similarities and were
      composed of predominantly solid growth of carcinoma cells, frequently with well
      developed vascular structures, in mammary ducts and ductules. Carcinoma cells
      were polygonal or occasionally spindle shaped and had fine-granular, relatively
      eosinophilic cytoplasm. The nuclei of these cells showed round to ovoid in shape
      and fine-granular chromatin pattern. There was not any invasive component, as
      confirmed by careful histological examination. Thus, additional
      immunohistochemical stainings for NE markers (chromogranin A and synaptophysin)
      were performed. Staining statuses of these markers were positive in almost all
      tumor cells from both breasts. Both tumors were therefore diagnosed as NE-DCIS.
      To our knowledge, this case is the first report of NE-DCIS diagnosed
      synchronously in both breasts.

PMID- 21735238
TI  - Phenolic lipid ingredients from cashew nuts.
AB  - Five new phenolic lipids, 2-(8"Z-eicosenoyl)-6-(8'Z-pentadecenyl) salicylic acid
      (3), 2-(9"Z-hexadecenoyl)-6-(8'Z, 11'Z-pentadecadienyl) methyl salicylate (5), 2
      (10"Z, 13"Z-nonadecadienoyl)-6-(8'Z, 11'Z-pentadecadienyl) salicylic acid (6), 2
      (16"Z-pentacosenoyl)-6-(8'Z-pentadecenyl) salicylic acid (7) and 2-(9"Z
      octadecenoyl)-6-(8'Z, 11'Z-pentadecadienyl) methyl salicylate (8), and three
      known compounds, cardols (1), anacardic acid (2) and cardanols (4), were isolated
      from the nuts of the cashew, Anacardium occidentale L. The structures were
      established on the basis of detailed MS and NMR spectroscopic analyses. Compound
      1 highly enhanced both Th-1 (IL-2, IFN-gamma) and Th-2 (IL-4, IL-5) cytokine
      production, and compounds 7 and 8 highly increased cytokine IL-2 and IFN-gamma
      production in response to concanavalin A in cultured murine Peyer's patch cells
      ex vivo. The isolated compounds showed moderate inhibitory activities on
      cytochrome CYP3A4 enzyme.

PMID- 21735239
TI  - Comparative study of final visual outcome between open- and closed-globe injuries
      following surgical treatment of traumatic cataract.
AB  - OBJECTIVE: The objective of this work is to compare final visual outcomes in
      cases of surgically treated traumatic cataract between open-globe and closed
      globe groups, as classified by the Birmingham Eye Trauma Terminology system.
      DESIGN: Observational cohort study. SETTING: Tertiary eye-care center at the
      trijunction of Gujarat, Madhya Pradesh, and Rajasthan states in central western
      India. METHODS: We enrolled patients meeting specific inclusion criteria,
      examined their eyes to review any co-morbidities due to trauma, performed surgery
      for traumatic cataracts, and implanted lenses. The patients were re-examined 6
      weeks postoperatively. We classified the cases of traumatic cataract as either
      open-globe (group 1) or closed-globe (group 2), according to the Birmingham Eye
      Trauma Terminology (BETT) system, and compared visual acuity. OUTCOME MEASURES:
      Visual Acuity. RESULTS: Our cohort of 687 eyes with traumatic cataracts included
      496 eyes in group 1 and 191 in group 2. Six weeks postoperatively, the visual
      acuity was >20/60 in 298 (58%) and 75 (39.1%) operated eyes in groups 1 and 2,
      respectively (p < 0.001, ANOVA). At follow-up, >20/60 vision was significantly
      higher in group 1 than in group 2 (OR = 1.61; 95% CI, 0.85-3.02). Overall, 373
      eyes (54.3%) regained final visual acuity >20/60. CONCLUSIONS: Open-globe injury
      has a more favorable prognosis for satisfactory (>20/60) visual recovery after
      management of traumatic cataracts.

PMID- 21735240
TI  - The novel use of decorin in prevention of the development of proliferative
      vitreoretinopathy (PVR).
AB  - BACKGROUND: The cytokine transforming growth factor-beta (TGF-beta) is a pivotal
      contributor to tissue fibrosis and a key cytokine in the pathogenesis of cellular
      transdifferentiation, epithelial-mesenchymal transition (EMT), and cell adhesion.
      This study evaluates the effect of decorin, a naturally occurring TGF-beta
      inhibitor, in an experimental rabbit model for proliferative vitreoretinopathy
      (PVR). METHODS: Traumatic PVR was induced in 50 rabbits divided into ten groups
      (n = 5). One group (GI) reveals a control with no treatment after trauma. Groups
      (GII-GIV) consisted of subgroups receiving phacovitrectomy at three different
      time points; (a) at the time of trauma, (b) 1 week following trauma, and (c) 2
      weeks following trauma. GIII and GIV received 100 MUg or 200 MUg decorin,
      respectively. PVR severity was scored from 0 to 4. The amount of fibrosis was
      quantified using JMicroVision(c) software. RESULTS: The control group GI
      developed severe PVR with tractional retinal detachment (TRD); (PVR score >=2) in
      four rabbits out of five. Vitrectomy had a positive effect (p < 0.05) on PVR
      development when preformed immediately, however the developed fibrosis was high.
      The best results were obtained when surgery was used in conjunction with decorin
      that reduced both the PVR score and fibrosis development significantly (p <
      0.05). Depending on dosage and time of vitrectomy, PVR could be completely
      avoided (PVR score = 0) in 16 rabbits out of 30. TRD was prevented in 13 rabbits
      out of 15 in GIII to 14 rabbits out of 15 in GIV. In decorin-treated eyes,
      vitrectomy outcome was best when preformed at 1 week after trauma. There were no
      drug-related toxic effects evident on clinical and histopathological examination.
      CONCLUSIONS: In conclusion, in this rabbit model of PVR, adjuvant decorin
      application during vitrectomy effectively reduces fibrosis and TRD development.
      In conjunction with no obvious histopathological toxicity signs, decorin
      represents a promising substance to inhibit PVR reactions.

PMID- 21735241
TI  - Effects of replacing fish meal by soybean meal along with supplementing
      phosphorus and magnesium in diet on growth performance of Persian sturgeon,
      Acipenser persicus.
AB  - Looking for replacing fish meal by cheaper and more sustainable protein sources
      is essential for reducing the cost of fish feeds. Soybean meal is a suitable
      alternative protein sources for carnivorous fish such as Persian sturgeon,
      Acipenser persicus. However, it contains antinutritional factors that may affect
      bioavailability of minerals and lead in reduced growth. Achieving a cost
      effective diet that does not have negative effects on growth is the goal of
      aquaculture programs. A 10-week experiment was conducted with Persian sturgeon
      (352.07 +/- 5.51 g) to determine the combined effects of phosphorous (SP),
      magnesium and phosphorous (SPMg), phytase (SF), phytase and magnesium (SFMg),
      phosphorous and phytase (SPF), phosphorous, magnesium and phytase (SPMgF) on
      weight gain, feed efficiency, specific growth rate, and condition factor. A
      control diet was prepared with fish meal as a control group. Inclusion of P, Mg,
      and phytase contents within soybean diets did not improve feed efficiency, and
      still, the control diet containing fish meal showed better weight gain and feed
      efficiency. Among soybean meal groups, feed efficiency and specific growth rate
      were significantly improved for fish fed the diet containing just phytase (SF)
      and both phytase and phosphorus (P <= 0.05). It was true for specific growth rate
      and condition factor. Phytase significantly enhanced growth whether included with
      or without phosphorous. This study showed that fish meal is more sufficient for
      Persian sturgeon, and soybean meal could be partly an alternative protein source
      if phosphorous supplied for fish by incorporation with microbial phytase or
      phosphorous.

PMID- 21735242
TI  - Bone morphology allows estimation of loading history in a murine model of bone
      adaptation.
AB  - Bone adapts its morphology (density/micro- architecture) in response to the local
      loading conditions in such a way that a uniform tissue loading is achieved
      ('Wolff's law'). This paradigm has been used as a basis for bone remodeling
      simulations to predict the formation and adaptation of trabecular bone. However,
      in order to predict bone architectural changes in patients, the physiological
      external loading conditions, to which the bone was adapted, need to be
      determined. In the present study, we developed a novel bone loading estimation
      method to predict such external loading conditions by calculating the loading
      history that produces the most uniform bone tissue loading. We applied this
      method to murine caudal vertebrae of two groups that were in vivo loaded by
      either 0 or 8 N, respectively. Plausible load cases were sequentially applied to
      micro-finite element models of the mice vertebrae, and scaling factors were
      calculated for each load case to derive the most uniform tissue strain-energy
      density when all scaled load cases are applied simultaneously. The bone loading
      estimation method was able to predict the difference in loading history of the
      two groups and the correct load magnitude for the loaded group. This result
      suggests that the bone loading history can be estimated from its morphology and
      that such a method could be useful for predicting the loading history for bone
      remodeling studies or at sites where measurements are difficult, as in bone in
      vivo or fossil bones.

PMID- 21735243
TI  - Tenocyte contraction induces crimp formation in tendon-like tissue.
AB  - Tendons are composed of longitudinally aligned collagen fibrils arranged in
      bundles with an undulating pattern, called crimp. The crimp structure is
      established during embryonic development and plays a vital role in the mechanical
      behaviour of tendon, acting as a shock-absorber during loading. However, the
      mechanism of crimp formation is unknown, partly because of the difficulties of
      studying tendon development in vivo. Here, we used a 3D cell culture system in
      which embryonic tendon fibroblasts synthesise a tendon-like construct comprised
      of collagen fibrils arranged in parallel bundles. Investigations using polarised
      light microscopy, scanning electron microscopy and fluorescence microscopy showed
      that tendon constructs contained a regular pattern of wavy collagen fibrils.
      Tensile testing indicated that this superstructure was a form of embryonic crimp
      producing a characteristic toe region in the stress-strain curves. Furthermore,
      contraction of tendon fibroblasts was the critical factor in the buckling of
      collagen fibrils during the formation of the crimp structure. Using these
      biological data, a finite element model was built that mimics the contraction of
      the tendon fibroblasts and monitors the response of the Extracellular matrix. The
      results show that the contraction of the fibroblasts is a sufficient mechanical
      impulse to build a planar wavy pattern. Furthermore, the value of crimp
      wavelength was determined by the mechanical properties of the collagen fibrils
      and inter-fibrillar matrix. Increasing fibril stiffness combined with constant
      matrix stiffness led to an increase in crimp wavelength. The data suggest a novel
      mechanism of crimp formation, and the finite element model indicates the minimum
      requirements to generate a crimp structure in embryonic tendon.

PMID- 21735244
TI  - Head position modulates optokinetic nystagmus.
AB  - Orientation and movement relies on both visual and vestibular information mapped
      in separate coordinate systems. Here, we examine how coordinate systems interact
      to guide eye movements of rabbits. We exposed rabbits to continuous horizontal
      optokinetic stimulation (HOKS) at 5 degrees /s to evoke horizontal eye movements,
      while they were statically or dynamically roll-tilted about the longitudinal
      axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30
      degrees  onto the side of the eye stimulated in the posterior -> anterior (P ->
      A) direction, slow phase eye velocity (SPEV) increased by 3.5-5 degrees /s. When
      the rabbit was roll-tilted 30 degrees  onto the side of the eye stimulated in the
      A -> P direction, SPEV decreased to ~2.5 degrees /s. We also tested the effect of
      roll-tilt after prolonged optokinetic stimulation had induced a negative
      optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the
      dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the
      nystagmus and was consistent with that observed during "closed loop" HOKS.
      Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude
      and the phase of SPEV depended on the frequency of vestibular oscillation and on
      HOKS velocity. We conclude that the change in the linear acceleration of the
      gravity vector with respect to the head during roll-tilt modulates the gain of
      SPEV depending on its direction. This modulation improves gaze stability at
      different image retinal slip velocities caused by head roll-tilt during centric
      or eccentric head movement.

PMID- 21735245
TI  - Grip forces during object manipulation: experiment, mathematical model, and
      validation.
AB  - When people transport handheld objects, they change the grip force with the
      object movement. Circular movement patterns were tested within three planes at
      two different rates (1.0, 1.5 Hz) and two diameters (20, 40 cm). Subjects
      performed the task reasonably well, matching frequencies and dynamic ranges of
      accelerations within expectations. A mathematical model was designed to predict
      the applied normal forces from kinematic data. The model is based on two
      hypotheses: (a) the grip force changes during movements along complex
      trajectories can be represented as the sum of effects of two basic commands
      associated with the parallel and orthogonal manipulation, respectively; (b)
      different central commands are sent to the thumb and virtual finger (Vf-four
      fingers combined). The model predicted the actual normal forces with a total
      variance accounted for of better than 98%. The effects of the two components of
      acceleration-along the normal axis and the resultant acceleration within the
      shear plane-on the digit normal forces are additive.

PMID- 21735246
TI  - Force synchrony enhances the stability of rhythmic multi-joint arm coordination.
AB  - Although rhythmic coordination has been extensively studied in the literature,
      questions remain about the correspondence of constraints that have been
      identified in the related contexts of inter-limb and intra-limb coordination.
      Here we used a 2-DOF robot arm which allows flexible manipulation of forces to
      investigate the effect on coordination stability of intra-limb coordination of:
      (i) the synchrony of force requirements and (ii) the involvement of bi-functional
      muscles. Ten subjects produced simultaneous rhythmic flexion-extension (FE) and
      supination-pronation (SP) elbow movements in two coordination patterns: (1)
      flexion synchronized with supination/extension with pronation (in-phase pattern)
      and (2) flexion synchronized with pronation/extension with supination (anti-phase
      pattern). The movements were produced with five different settings of the robot
      arm: a neutral setting that imposed balanced force requirements, and four other
      settings that increased the force requirements for one direction in both DOF.
      When combined with specific coordination patterns, these settings created
      conditions in which either synchronous or alternate patterns of forcing were
      necessary to perform the task. Results showed that synchronous tasks were more
      stable than asynchronous tasks (P < 0.05). Within the synchronous tasks, some
      robot settings were designed to either increase or decrease the use of bi
      functional muscles. Although there was no difference for the bi-functional muscle
      biceps brachii, the coordination was more stable for the condition in which the
      greatest force requirements corresponded to the mechanical action of the bi
      functional pronator teres (P < 0.05). In conclusion, force synchrony increases
      the stability of rhythmic intra-limb coordination, but further research is needed
      to clarify the role of bi-functional muscles in this effect.

PMID- 21735247
TI  - Error awareness and antisaccade performance.
AB  - In the antisaccade task, healthy participants often make errors by saccading
      towards the sudden onset target, despite instructions to saccade to the mirror
      image location. One interesting and relatively unexplored feature of antisaccade
      performance is that participants are typically unaware of a large proportion of
      the errors they make. Across two experiments, we explored the extent to which
      error awareness is altered by manipulations known to affect antisaccade error
      rate. In experiment 1, participants performed the antisaccade task under standard
      instructions, instructions to respond as quickly as possible or instructions to
      delay responding. Delay instructions significantly reduced antisaccade error rate
      compared to the other instructions, but this reduction was driven by a decrease
      only in the number of errors that participants were aware of-the number of errors
      of which participants were unaware remained constant across instruction
      condition. In experiment 2, participants performed antisaccades alone, or
      concurrently with two different distractor tasks-spatial tapping and random
      number generation task. Both the dual task conditions increased the number of
      errors of which participants were aware, but again, unaware error rates remained
      unchanged. These results are discussed in the light of recent models of
      antisaccade performance and the role of conscious awareness in error correction.

PMID- 21735248
TI  - ORchestra: an online reference database of OR/MS literature in health care.
AB  - We introduce the categorized reference database ORchestra, which is available
      online at http://www.utwente.nl/choir/orchestra/.

PMID- 21735249
TI  - Factors related to high and low levels of drug adherence according to patients
      with type 2 diabetes.
AB  - OBJECTIVE: Adherence to medication in patients with type 2 diabetes varies
      widely, yet the factors that influence adherence according to patients are not
      fully known. The aim of this study is to explore both factors related to high and
      lower levels of adherence that patients with type 2 diabetes experienced in their
      medication use. SETTING: Primary care in the Netherlands. METHOD: Qualitative,
      semi-structured interviews were performed in 20 patients with type 2 diabetes.
      Interviews were audio-taped and transcribed verbatim. Transcripts were coded and
      analysed using content analysis and constant comparison. Main outcome measure
      experiences and opinions of patients concerning factors related to high and lower
      levels of adherence. RESULTS: Comparable aspects influenced drug adherence in
      more and less adherent patients. Four aspects that influenced adherence to
      medication emerged from the interviews: (1) information about the prescribed
      medication, (2) experience with medication and complications with use, (3) social
      support for medication behaviour and (4) routines in medication behaviour.
      Experience with medication and social support for medication behaviour were
      related to high levels of adherence in some patients, and to lower levels of
      adherence in others. Complicated medication regimens were mainly related to lower
      adherence, while social support and routines in medication behaviour were related
      to higher adherence. CONCLUSIONS: Routines in medication behaviour were related
      to higher drug adherence. Patient education should not only address information
      about the disease and medication, but also more practical issues concerning drug
      intake. Hence, to improve drug adherence in patients with type 2 diabetes,
      pharmaceutical care might be aimed at the counselling of patients to organise
      drug use in their daily schedule.

PMID- 21735250
TI  - Breast tissue image classification based on Semi-supervised Locality Discriminant
      Projection with Kernels.
AB  - Breast tissue classification is an important and effective way for computer aided
      diagnosis of breast cancer. We present Semi-supervised Locality Discriminant
      Projections with Kernels for breast cancer classification. The contributions of
      this work lie in: 1) Semi-supervised learning is used into Locality Preserving
      Projections (LPP) to enhance its performance using side-information together with
      the unlabelled training samples, while current algorithms only consider the side
      information but ignoring the unlabeled training samples. 2) Kernel trick is
      applied into Semi-supervised LPP to improve its ability in the nonlinear
      classification. 3) The framework of breast cancer classification with Semi
      supervised LPP with kernels is presented. Many experiments are implemented on
      four breast tissue databases to testify and evaluate the feasibility and
      affectivity of the proposed scheme.

PMID- 21735251
TI  - Computer-assisted diagnosis of tuberculosis: a first order statistical approach
      to chest radiograph.
AB  - Textural properties of normal and tuberculosis posterior-anterior chest
      radiographs were looked into in this investigation. The proposed computerized
      scheme segmented the lung field of interest using a user-guided snake algorithm
      and extracted the corresponding pixel data. For both normal and tuberculosis
      radiographs, the grayscale intensity distribution within the region of interest
      was analyzed to study their respective characteristics, and fed to classifiers
      for automated classification. Statistically the tuberculosis infected radiographs
      manifested a higher variance, third moment, entropy and a lower mean value in
      their intensity distributions, compared to their normal peers. The greater
      disparities between a particular radiograph and the confidence interval
      determined by our normal groups on some of the features were observed to be
      related to the level of haziness at the upper lobe. Lastly, the C4.5 (a decision
      tree based classifier)-adaboost achieved an accuracy of 94.9% in normal
      tuberculosis classification. An integrated index, called tuberculosis index (TI),
      is proposed based on texture features to discriminate normal and tuberculosis
      chest radiographs using just one index or number. We hope this TI can be used as
      an adjunct tool by the radiographers in their daily screening.

PMID- 21735252
TI  - New insights into glioma classification based on isocitrate dehydrogenase 1 and 2
      gene status.
AB  - In glioma, mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) genes have
      been receiving attention. IDH1/2 mutations are frequently found in grade II and
      III gliomas. These genetic alterations occur very early in gliomagenesis and
      strongly predict favorable outcome in patients with high-grade gliomas. Despite
      the evolution of studies on this topic, the underlying mechanism of the IDH1/2
      mutations remains unknown. Here, we briefly review the current knowledge of
      IDH1/2 and discuss molecular diagnostics based on IDH1/2 gene status.

PMID- 21735253
TI  - 'Lassoing' a phylogenetic tree I: basic properties, shellings, and covers.
AB  - A classical result, fundamental to evolutionary biology, states that an edge
      weighted tree T with leaf set X, positive edge weights, and no vertices of degree
      2 can be uniquely reconstructed from the leaf-to-leaf distances between any two
      elements of X. In biology, X corresponds to a set of taxa (e.g. extant species),
      the tree T describes their phylogenetic relationships, the edges correspond to
      earlier species evolving for a time until splitting in two or more species by
      some speciation/bifurcation event, and their length corresponds to the genetic
      change accumulating over that time in such a species. In this paper, we
      investigate which subsets of [Formula: see text] suffice to determine ('lasso')
      the tree T from the leaf-to-leaf distances induced by that tree. The question is
      particularly topical since reliable estimates of genetic distance-even (if not in
      particular) by modern mass-sequencing methods-are, in general, available only for
      certain combinations of taxa.

PMID- 21735254
TI  - [Treatment of bacterial infection in the interphalangeal joints of the hand].
AB  - OBJECTIVE: Radical debridement of joint infection, prevention of further
      infection-related tissue destruction. INDICATIONS: Septic arthritis of
      interphalangeal joints in the thumb and fingers. CONTRAINDICATIONS: Extensive
      soft tissue defects. Severe impairment of blood circulation, finger gangrene.
      Noncompliance for immobilization or for treatment with external fixator. SURGICAL
      TECHNIQUE: Arthrotomy and irrigation with isotonic solution. Radical tissue
      debridement. Joint preservation possible only in the absence of infection-related
      macroscopic cartilage damage. Otherwise, resection of the articular surfaces and
      secondary arthrodesis. Insertion of antibiotic-coated devices. Temporary
      immobilization with external fixator. POSTOPERATIVE MANAGEMENT: Inpatient
      postoperative treatment with 5-day intravenous administration of a second
      generation cephalosporine (e.g., Cefuroxim(r)) followed by 7-10 days oral
      application. Adaptation of antibiotics according to antibiogram results. In joint
      preserving procedures, radiographs and fixator removal after 4 weeks, active
      joint mobilization. If joint surfaces were resected, removal of fixator after 6
      weeks; arthrodesis under 3-day intravenous broad-band antibiotic prophylaxis.
      Splint immobilization until consolidation (6-8 weeks). RESULTS: In 10 of 40
      patients, the infected joint could be preserved. All infections healed. After an
      average duration of therapy of 6 (3-11) weeks, 4 individuals were free of
      complaints, and 6 patients had minor symptoms. Overall range of motion in the
      affected finger was reduced by 25-50 degrees  in 5 patients. All patients could
      return to work after 6.6 (4-11) weeks. A total of 30 patients were treated with
      joint resection and external fixator. After 5.6 (4-8) weeks, arthrodesis was
      performed, leading to consolidation in 29 patients. One patient underwent
      amputation after 4 months due to delayed gangrene. Treatment duration was 15.7 (7
      25) weeks. Eight patients reported no complaints, 14 suffered mild symptoms, 5
      had moderate, and 3 had severe symptoms in daily life. In 15 cases, range of
      motion was diminished by 10-80 degrees  in the remaining joints of the affected
      finger. Patients could return to work after 16.2 (6-28) weeks.

PMID- 21735255
TI  - Original landmarks for intraoperative localization of the foramen ovale: a radio
      anatomical study.
AB  - PURPOSE: Radiofrequency lesioning is one of the frequently used modalities for
      the treatment of trigeminal neuralgia. Easily identifiable radiological landmarks
      are necessary for correct intra-operative localization of foramen ovale. METHODS:
      One hundred and seventy sides of dry skulls were studied for the following
      measurements. D-1: the transverse distance between the apex of the petrous
      temporal and the centre of the foramen ovale. D-2: the transverse distance from
      the midline to the centre of the foramen ovale. The distances between the centre
      of the foramen ovale and, D-3: the anterior margin of mandibular fossa, D-4:
      centre of the mandibular fossa and D-5: point at the junction of posterior margin
      and floor of the sella. D-6: the vertical distance between the centre of the
      foramen ovale and point at the junction of posterior margin and floor of the
      sella. RESULTS: The mean values measured were D-1: 13.9 mm, D-2: 24.5 mm, D-3:
      3.1 mm, D-4: 11.4 mm, D-5: 0.75 and D-6: 12.42 mm. In majority of cases the
      centre of foramen was around 25 mm from midline. Additionally the centre of the
      foramen was at the level of the junction of the posterior wall and floor of the
      sella or within 2 mm of this point in the antero-posterior direction. In most
      (81%) cases the vertical displacement of the foramen was 1-1.5 cm inferior to
      this point. CONCLUSION: During intra-operative imaging, the midline of the skull
      and the junction of the posterior wall and floor of the sella can be used as
      reliable landmarks for the identification of foramen ovale.

PMID- 21735257
TI  - Expression and purification of antimicrobial peptide buforin IIb in Escherichia
      coli.
AB  - A novel production method in Escherichia coli for an antimicrobial peptide of 21
      amino acids, buforin IIb, which is a synthetic analog of buforin II, has been
      developed. The buforin IIb gene was cloned into the vector pET32a to construct an
      expression vector pET32a-buforin IIb. The fusion protein Trx-buforin IIb,
      purified by nickel nitrilo-triacetic acid (Ni-NTA) resin chromatography, was
      cleaved by hydroxylamine hydrochloride to release recombinant buforin IIb.
      Purification of recombinant buforin IIb was achieved by HPLC: about 3.1 mg/l
      active recombinant buforin IIb with purity >99% was obtained. The recombinant
      buforin IIb showed antimicrobial activities that were similar to the synthetic
      one.

PMID- 21735258
TI  - Over-expression of chloroperoxidase in Caldariomyces fumago.
AB  - The filamentous fungus Caldariomyces fumago secretes a chloroperoxidase (CPO). To
      increase its production, we integrated a CPO-expression cassette into the non
      transcribed spacer regions of the rDNA in C. fumago. One strain was obtained that
      had twice the CPO activity when grown in shake-flask and bioreactor compared to
      the wild-type. The highest CPO activity from the bioreactor cultivation was 3,236
      U ml(-1). This is the highest value reported so far.

PMID- 21735259
TI  - Construction and characterization of a fusion beta-1,3-1,4-glucanase to improve
      hydrolytic activity and thermostability.
AB  - A new fusion gene (Bgl-licMB), encoding beta-1,3-1,4-glucanase both from Bacillus
      amyloliquefaciens (Bgl) and Clostridium thermocellum (licMB), was constructed via
      end-to-end fusion and expressed in Escherichia coli to improve hydrolytic
      activity and thermostability of beta-1,3-1,4-glucanase. The results of enzymatic
      properties showed that the catalytic efficiency (K(cat)/K(m)) of the fusion
      enzyme for oat beta-glucan was 2.7 and 20-fold higher than that of the parental
      Bgl and licMB, respectively, and that the fusion enzyme can retain more than 50%
      of activity following incubation at 80 degrees C for 30 min, whereas the residual
      activities of Bgl and licMB were both less than 30%. These properties make this
      particular beta-1,3-1,4-glucanase a good candidate for application in brewing and
      animal-feed industries.

PMID- 21735260
TI  - Discovery of novel inhibitors for human intestinal maltase: virtual screening in
      a WISDOM environment and in vitro evaluation.
AB  - Human intestinal maltase (HMA) is an alpha-glucosidase that hydrolyses alpha-1,4
      linkages from the non-reducing end of malto-oligosaccharides. HMA is an important
      target to discover of new drugs for the treatment of type 2 diabetes. In this
      study, 308,307 compounds were virtually screened with HMA using Autodock 3.0.5 in
      a WISDOM production environment to discover novel inhibitors. The 42 top-scoring
      free binding energy compounds, representing 17 groups containing potential
      hydrogen bonding with key residues in the active site pocket of HMA, were tested
      in vitro for their inhibitory activities against recombinant HMA expressed from
      Pichia pastoris. Compounds 17 and 18 were competitive inhibitors exclusively for
      HMA without any in vitro inhibition for human pancreatic alpha-amylase. The K(i)
      values were 20 MUM for both compound 17 and 18.

PMID- 21735261
TI  - Free energy calculations offer insights into the influence of receptor
      flexibility on ligand-receptor binding affinities.
AB  - Docking algorithms for computer-aided drug discovery and design often ignore or
      restrain the flexibility of the receptor, which may lead to a loss of accuracy of
      the relative free enthalpies of binding. In order to evaluate the contribution of
      receptor flexibility to relative binding free enthalpies, two host-guest systems
      have been examined: inclusion complexes of alpha-cyclodextrin (alphaCD) with 1
      chlorobenzene (ClBn), 1-bromobenzene (BrBn) and toluene (MeBn), and complexes of
      DNA with the minor-groove binding ligands netropsin (Net) and distamycin (Dist).
      Molecular dynamics simulations and free energy calculations reveal that
      restraining of the flexibility of the receptor can have a significant influence
      on the estimated relative ligand-receptor binding affinities as well as on the
      predicted structures of the biomolecular complexes. The influence is particularly
      pronounced in the case of flexible receptors such as DNA, where a 50%
      contribution of DNA flexibility towards the relative ligand-DNA binding
      affinities is observed. The differences in the free enthalpy of binding do not
      arise only from the changes in ligand-DNA interactions but also from changes in
      ligand-solvent interactions as well as from the loss of DNA configurational
      entropy upon restraining.

PMID- 21735262
TI  - Small intestinal tumors: diagnostic accuracy of enhanced multi-detector CT
      virtual endoscopy.
AB  - OBJECTIVE: To study the diagnostic accuracy of enhanced multi-detector CT virtual
      endoscopy (MDCT-VE) for small intestinal tumors. MATERIALS AND METHODS: 125
      patients were examined by multi-detector CT (MDCT: 54 on 4-slice; 71 on 64-slice)
      following standard gastrointestinal tract cleansing, oral double contrast
      aerogenesis agent, and rectal gas administration. Unenhanced CT was performed,
      followed by enhanced CT in supine (30 and 80s delay after 100 mL standard
      intravenous contrast medium) and prone positions (180s delay). Supplementary CT
      in the lateral position was performed if small bowel was not well-filled. Images
      were reviewed on post-processing workstations with Virtual Endoscopy software.
      RESULTS: 33/125 patients had proven small intestinal tumors: ten stromal tumors,
      nine lymphoma, eight adenocarcinomas, three hemangiomas, one each lipoma, Brunner
      gland adenoma, and hamartoma. 92 were nontumors. MDCT-VE correctly identified
      30/33 cases with one false-positive diagnosis: sensitivity 90.9%, specificity
      98.9% and accuracy 96.8%. CONCLUSION: Small intestinal MDCT-VE technique has high
      diagnostic accuracy for the detection of intestinal tumors. Contrast enhancement
      and adequate intestinal tract gas-filling can improve the detection rate for
      small intestinal tumors.

PMID- 21735263
TI  - Characterization of sulfide-oxidizing microbial mats developed inside a full
      scale anaerobic digester employing biological desulfurization.
AB  - The microbial mats responsible for biological desulfurization from biogas in a
      full-scale anaerobic digester were characterized in terms of their structure, as
      well as their chemical and microbial properties. Filament-shaped elemental sulfur
      100-500 MUm in length was shown to cover the mats, which cover the entire
      headspace of the digester. This is the first report on filamentous sulfur
      production in a non-marine environment. The results of the analysis of the mats
      suggest that the key players in the sulfide oxidation and sulfur production in
      the bio-desulfurization in the headspace of the digester were likely to be two
      sulfide-oxidizing bacteria (SOB) species related to Halothiobacillus neapolitanus
      and Sulfurimonas denitrificans, and that the microbial community, cell density,
      activity for sulfide oxidation varied according to the environmental conditions
      at the various locations of the mats. Since the water and nutrients necessary for
      the SOB were provided by the digested sludge droplets deposited on the mats, and
      our results show that a higher rate of sulfide oxidation occurred with more
      frequent digested sludge deposition, the habitat of the SOB needs to be made in
      the lower part of the headspace near the liquid level of the digested sludge to
      maintain optimal conditions.

PMID- 21735264
TI  - Scientific challenges of bioethanol production in Brazil.
AB  - Bioethanol (fuel alcohol) has been produced by industrial alcoholic fermentation
      processes in Brazil since the beginning of the twentieth century. Currently, 432
      mills and distilleries crush about 625 million tons of sugarcane per crop,
      producing about 27 billion liters of ethanol and 38.7 million tons of sugar. The
      production of bioethanol from sugarcane represents a major large-scale technology
      capable of producing biofuel efficiently and economically, providing viable
      substitutes to gasoline. The combination of immobilization of CO2 by sugarcane
      crops by photosynthesis into biomass together with alcoholic fermentation of this
      biomass has allowed production of a clean and high-quality liquid fuel that
      contains 93% of the original energy found in sugar. Over the last 30 years,
      several innovations have been introduced to Brazilian alcohol distilleries
      resulting in the improvement of plant efficiency and economic competitiveness.
      Currently, the main scientific challenges are to develop new technologies for
      bioethanol production from first and second generation feedstocks that exhibit
      positive energy balances and appropriately meet environmental sustainability
      criteria. This review focuses on these aspects and provides special emphasis on
      the selection of new yeast strains, genetic breeding, and recombinant DNA
      technology, as applied to bioethanol production processes.

PMID- 21735265
TI  - Beta-zone parapapillary atrophy and multifocal visual evoked potentials in eyes
      with glaucomatous optic neuropathy.
AB  - We investigated changes in multifocal visual evoked potential (mfVEP) responses
      due to beta-zone parapapillary atrophy (betaPPA). Patients with glaucomatous
      optic neuropathy (GON) with or without standard achromatic perimetry (SAP)
      abnormalities were referred for mfVEP testing during a 2-year period. Eyes with
      good quality optic disc stereophotographs and reliable SAP results were included.
      The mfVEP monocular mean latency delays (ms) and amplitudes (SNR) were analyzed.
      Age, SAP mean deviation (MD), pattern standard deviation (PSD), and spherical
      equivalent (SE) were analyzed in the multivariate model. Generalized estimated
      equations were used for comparisons between groups after adjusting for inter-eye
      associations. Of 394 eyes of 200 patients, 223 (57%) had betaPPA. The betaPPA
      eyes were older (59.6 +/- 13.7 vs. 56.5 +/- 13.7 year, P = 0.02), more myopic (
      4.0 +/- 3.5 vs. -1.3 +/- 3.5 D, P < 0.01), and had poorer SAP scores (MD: -4.9 +/
      5.2 vs. -2.6 +/- 5.2 dB, P < 0.01; PSD: 4.3 +/- 2.9 vs. 2.5 +/- 3.0 dB, P <
      0.01). By univariate analysis, mean latencies were longer in betaPPA eyes (6.1 +/
      5.3 vs. 4.0 +/- 5.5 ms, P < 0.01). After adjusting for differences in SE, age,
      and SAP MD, there was no significant difference between the two groups (P =
      0.09). betaPPA eyes had lower amplitude log SNR (0.49 +/- 0.16 vs. 0.56 +/- 0.15,
      P < 0.01), which lost significance (P = 0.51) after adjusting for MD and PSD.
      Although eyes with betaPPA had significantly lower amplitudes and prolonged
      latencies than eyes without betaPPA, these differences were attributable to
      differences in SAP severity, age, and refractive error. Thus, betaPPA does not
      appear to be an independent factor affecting mfVEP responses in eyes with GON.

PMID- 21735266
TI  - The effects of 4-thujanol on chromosome aberrations, sister chromatid exchanges
      and micronucleus in human peripheral blood lymphocytes.
AB  - 4-Thujanol, a bicyclic monoterpene alcohol, is present in the essential oils of
      many medicinal and aromatic plants. It is commonly used as a fragrance and
      flavouring ingredient in a lot of different products. The potential genotoxic
      effects of 4-thujanol on human peripheral blood lymphocytes (PBLs) were
      investigated in vitro by the chromosome aberrations (CAs), sister chromatid
      exchanges (SCEs), and micronucleus (MN) tests. The cells were treated with 13, 26
      and 52 MUg/mL 4-thujanol in the presence and absence of a metabolic activator (S9
      mix). 4-Thujanol induced CA (P < 0.001) and MN formation (P < 0.05) at all
      concentrations (13, 26 and 52 MUg/mL) in the presence and absence of the S9 mix
      without a concentration-dependent manner. However, the treatment of peripheral
      lymphocytes with 4-thujanol did not produce a statistical difference in the
      frequency of SCEs when compared with control group. Furthermore, this monoterpene
      did not significantly decrease the mitotic index (MI), proliferation index (PI),
      and nuclear division index (NDI). In conclusion, 4-thujanol had a significant
      clastogenic effect at the tested concentrations (13, 26 and 52 MUg/mL) for human
      PBLs. In addition, no cytotoxic and/or cytostatic effects were observed
      regardless of the concentrations used. This work presents the first report on
      genotoxic properties of 4-thujanol.

PMID- 21735267
TI  - [Oncological and functional results of open intrafascial radical prostatectomy].
AB  - BACKGROUND: According to the recently published German-language S3 guidelines,
      various treatment options such as surgical management or radiation therapy are
      available to patients with locally advanced prostate cancer. METHODS:
      Particularly the establishment of minimally invasive endoscopic surgical
      techniques, which provide better optical images, has made it possible to
      visualize tissue layers that are usually difficult to identify with the open
      surgical technique. This contribution describes a pilot study on the
      establishment of open intrafascial radical prostatectomy. AIM: The goal of the
      study is to critically analyze both the functional and especially the oncological
      results, which should not be compromised by the nerve-sparing approach.

PMID- 21735268
TI  - [Genotype of the GNB3 C825T polymorphism, A risk factor for the development and
      course of prostate cancer?].
AB  - BACKGROUND: G protein-mediated signal transduction plays a key role in pathways
      of metastasis. A C/T polymorphism (dbSNP rs5443) at position 825 of the GNB3 gene
      has been described. Previous studies demonstrated an association between the GNB3
      C825T genotype and different cancer entities. PATIENTS AND METHODS: In this
      report genotyping for this marker was performed in 235 prostate cancer patients
      and 111 healthy control subjects. Clinical follow-up data were available for a
      subset of 197 patients. RESULTS: Neither significant evidence for differences in
      genotype distributions between the prostate cancer cases and controls (odds ratio
      CT/TT=0.94, 95% CI 0.58-1.51, p=.82) nor evidence for genotype differences in
      e.g. progression-free survival in the subset of patients was observable (hazard
      ratio CT/TT=0.77, 95% CI 0.44-1.37, p=.38). Similar results were obtained in the
      subgroup of patients with primary tumor stage <= pT2 N0 M0 undergoing radical
      prostatectomy. CONCLUSION: Our data do not support an association between
      prostate cancer and the genotype of the GNB3 C825T polymorphism. This finding
      might either indicate a much smaller genetic effect undetectable with the given
      sample size or a possible hormone dependence of the disease superimposed on the
      potential effect of the GNB3 C825T genotype.

PMID- 21735269
TI  - [The future of uro-oncology: what needs to be done to secure its place in the
      field of urology?].
AB  - The specialty of urology has changed considerably with regard to the subspecialty
      of uro-oncology and requires more than just knowledge of hormone therapy for
      metastatic prostate cancer and standard treatment of testicular tumors. Many
      oncology centers offer specialized and interdisciplinary treatment, but often the
      process of navigating through the jungle of diagnostic workup and treatment is
      inadequate. Thus, clinical centers for uro-oncology must include specialists in
      pharmacological therapy for cancer and drug development who will work closely
      with the department of urology.

PMID- 21735270
TI  - Collagen atomic scale molecular disorder in ochronotic cartilage from an
      alkaptonuria patient, observed by solid state NMR.
AB  - In pilot studies of the usefulness of solid state nuclear magnetic resonance
      spectroscopy in characterizing chemical and molecular structural effects of
      alkaptonuria on connective tissue, we have obtained (13) C spectra from articular
      cartilage from an AKU patient. An apparently normal anatomical location yielded a
      cross polarization magic angle spinning spectrum resembling literature spectra
      and dominated by collagen and glycosaminoglycan signals. All spectral linewidths
      from strongly pigmented ochronotic cartilage however were considerably increased
      relative to the control indicating a marked increase in collagen molecular
      disorder. This disordering of cartilage structural protein parallels, at the
      atomic level, the disordering revealed at higher length scales by microscopy. We
      also demonstrate that the abnormal spectra from ochronotic cartilage fit with the
      abnormality in the structure of collagen fibres at the ultrastructural level,
      whereby large ochronotic deposits appear to alter the structure of the collagen
      fibre by invasion and cross linking. SUMMARY: Increased signal linewidths in
      solid state NMR spectra of ochronotic articular cartilage from an AKU patient
      relative to linewidths in normal, control, cartilage reveals a marked decrease in
      collagen molecular order in the diseased tissue. This atomic level disordering
      parallels higher length scale disorder revealed by microscopic techniques.

PMID- 21735271
TI  - MR evaluation of synovial injury in shoulder trauma.
AB  - The purpose of this study was to determine magnetic resonance imaging (MRI)
      findings relevant to synovial injury of the shoulder in patients with and without
      acute shoulder trauma. Three hundred and nine consecutive shoulder MRI studies
      (185-male, 124-female, 50 +/- 15 years old) were retrospectively evaluated for
      findings suggestive of synovial injury including rupture and/or diverticulum of
      the joint capsule, bursa, and biceps tendon sheath (BTS), ganglion/synovial cyst,
      geyser phenomenon, and sequel of previous shoulder dislocation (Hill-Sachs
      deformity). Patients with one or more of these findings were included in the MR
      positive group, whereas the remaining subjects were used as MR negatives. Based
      on their medical records, patients were also divided into trauma and non-trauma
      groups, and statistical analysis was performed to evaluate the association
      between the aforementioned MRI findings and history of shoulder trauma. Fifty-six
      patients were included in the MR-positive group and 253 in the MR-negative group.
      In MR-positive group, the incidence of capsular rupture (CR) and
      subacromial/subdeltoid (SASD) bursal rupture was higher in trauma patients,
      whereas the incidence of BTS diverticulum and ganglion cyst was higher in
      subjects without trauma. Significant association was found between the history of
      acute trauma and CR, SASD bursal rupture, BTS rupture, and Hill-Sachs deformity.
      In shoulder MR examination, presence of CR and/or SASD bursal rupture is strongly
      suggestive of acute shoulder trauma. In addition, BTS rupture and Hill-Sachs
      deformity are more prevalent in patients with acute shoulder trauma. The presence
      of these features should alert MRI readers to assess for additional trauma
      related internal derangements, if a respective history has not been provided.

PMID- 21735272
TI  - Templating alpha-amylase peptide inhibitors with organotin compounds.
AB  - Metal centers have been widely used to nucleate secondary structures in linear
      peptides. However, very few examples have been reported for peptide/organometal
      complexes. Here, we illustrate the use of organotin compounds as nucleation
      centers for secondary structures of linear peptide inhibitors of alpha-amylase.
      Specifically, we utilized methyl-substituted tin compounds to template short type
      I beta-turns similar to the binding loop of tendamistat, the natural inhibitor of
      the enzyme, which are able to bind and inhibit alpha-amylase. We show that enzyme
      activity is inhibited by neither the unstructured peptide nor the organotin
      compounds, but rather the peptide/organotin complex, which inhibits the enzyme
      with K (i) ~ 0.5 MUM. The results delineate a strategy to use organometallic
      compounds to drive the active conformation in small linear peptides.

PMID- 21735273
TI  - Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut
      extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7
      cells.
AB  - BACKGROUND: Positive effects of pistachio nut consumption on plasma inflammatory
      biomarkers have been described; however, little is known about molecular events
      associated with these effects. PURPOSE: We studied the anti-inflammatory activity
      of a hydrophilic extract from Sicilian Pistacia L. (HPE) in a macrophage model
      and investigated bioactive components relevant to the observed effects. METHODS:
      HPE oligomer/polymer proanthocyanidin fractions were isolated by adsorbance
      chromatography, and components quantified as anthocyanidins after acidic
      hydrolysis. Isoflavones were measured by gradient elution HPLC analysis. RAW
      264.7 murine macrophages were pre-incubated with either HPE (1- to 20-mg fresh
      nut equivalents) or its isolated components for 1 h, then washed before
      stimulating with lipopolysaccharide (LPS) for 24 h. Cell viability and parameters
      associated with Nuclear Factor-kappaB (NF-kappaB) activation were assayed
      according to established methods including ELISA, Western blot, or
      cytofluorimetric analysis. RESULTS: HPE suppressed nitric oxide (NO) and tumor
      necrosis factor-alpha (TNF-alpha) production and inducible NO-synthase levels
      dose dependently, whereas inhibited prostaglandin E2 (PGE2) release and decreased
      cyclo-oxygenase-2 content, the lower the HPE amount the higher the effect.
      Cytotoxic effects were not observed. HPE also caused a dose-dependent decrease in
      intracellular reactive oxygen species and interfered with the NF-kappaB
      activation. Polymeric proanthocyanidins, but not isoflavones, at a concentration
      comparable with their content in HPE, inhibited NO, PGE2, and TNF-alpha
      formation, as well as activation of IkappaB-alpha. Oligomeric proanthocyanidins
      showed only minor effects. CONCLUSIONS: Our results provide molecular evidence of
      anti-inflammatory activity of pistachio nut and indicate polymeric
      proanthocyanidins as the bioactive components. The mechanism may involve the
      redox-sensitive transcription factor NF-kappaB. Potential effects associated with
      pistachio nut consumption are discussed in terms of the proanthocyanidin
      bioavailability.

PMID- 21735274
TI  - Determination of mercury, cadmium, lead, zinc, selenium and iron by ICP-OES in
      mushroom samples from around thermal power plant in Mugla, Turkey.
AB  - Scleroderma verrucosum, Stropharia coronilla, Lactarius deterrimus, Chroogomphus
      rutilus, Russula delica, Laccaria laccata, Clitocybe odora var. alba, Lyophyllum
      decastes, Coprinus comatus, Helvella leucomelaena, Melanoleuca cognata,
      Melanoleuca cognata, Paxina acetabulum, Clitocybe vermicularis, Sarcosphaera
      crassa, Rhizopogon roseolu and Thelephora caryophyllea were collected from
      different localities in Mugla-Yatagan region of Turkey. Their trace metals
      concentrations were determined by ICPOES after microwave digestion. The results
      were 0.37 +/- 0.01-5.28 +/- 0.21 for cadmium, 467 +/- 19-3,280 +/- 131 for iron,
      0.69 +/- 0.03-9.15 +/- 0.37 for lead, 18.70 +/- 0.75-67.10 +/- 2.68 for selenium,
      75 +/- 3-213 +/- 8 for zinc and 0.15 +/- 0.01-0.55 +/- 0.01 for mercury (as
      MUg/g). The detection limits for ICPOES were found as 0.25 for Cadmium, 0.2 for
      iron, 0.1 for lead, 0.5 for selenium, 0.2 for zinc and 0.03 for mercury (as mg L(
      1)). The Relatively Standard Deviations (R.S.D.) were found below 4.0%. The
      accuracy of procedure was confirmed by certified reference material.

PMID- 21735275
TI  - Evaluation of estrogenic activity in surface water and municipal wastewater in
      Shanghai, China.
AB  - Estrogenic potency of water samples from various rivers and wastewater treatment
      plants (WWTPs) in Shanghai was determined to assess the estrogenic pollution in
      typical Chinese urban regions. While the estrogenic activity, calculated as
      estradiol equivalents (EEQs), in surface water was found to be 2.48-41.9 ng/L, it
      was 47.7-80.1 ng/L in the influents from WWTPs. After treatment (removal rate of
      62.3%-83.6%), the EEQ level in effluents was 7.82-24.8 ng/L, which was within the
      range of the corresponding receiving rivers. Our findings suggest that WWTP
      effluents may not be the predominate source of potential aquatic estrogenic
      contamination in Shanghai.

PMID- 21735276
TI  - Do breast cancer survivors' post-surgery difficulties with recreational
      activities persist over time?
AB  - INTRODUCTION: Most longitudinal breast cancer studies have found that treatment
      related sequelae such as arm morbidity [lymphedema, pain, and range of motion
      (ROM) restrictions] can have a significant impact on quality of life. In a
      previous study, we found that at 6-12 months after breast cancer surgery, 49% of
      participants had difficulties engaging in recreational activities and that arm
      morbidity significantly predicted difficulties with participation in recreation.
      METHODS: A longitudinal national study employing clinical assessments and survey
      methods followed 178 women over 43 months (3.6 years) to assess issues related to
      arm morbidity post-breast cancer surgery. Hierarchical multiple regression
      analyses were conducted to identify which variables were predictive of
      recreational difficulties experienced by women 8 and 43 months post-surgery.
      RESULTS: Between 8 months (T1) and 43 months (T2) post-breast cancer surgery,
      women demonstrated slight increases in lymphedema. Conversely, a significant
      decrease was observed in the number of ROM restrictions and pain when using the
      arm. Despite the overall improvements in arm morbidity, some women continued to
      report moderate pain and ROM restrictions. The two arm morbidity factors were
      found to be statistically significant (p < 0.001) predictors of recreational
      difficulties at both 8 and 43 months post-surgery, with pain accounting for the
      greatest proportion of variance. DISCUSSION/CONCLUSION: Pain and ROM restrictions
      were the only significant predictors of recreational difficulties during the
      first 3.6 years after breast cancer surgery. Specifically, women who still
      experience pain years after breast cancer surgery report difficulties in their
      recreational pursuits. IMPLICATIONS FOR CANCER SURVIVORS: Pain and ROM
      restrictions may prohibit participation in recreational activity and targeted
      intervention should be sought.

PMID- 21735277
TI  - Breast and colorectal cancer survivors' knowledge about their diagnosis and
      treatment.
AB  - INTRODUCTION: Aspects of a personal cancer history can have implications for
      future decisions regarding screening, diagnosis, and treatment. Clinicians must
      sometimes rely on patients' self-report of their medical history. This study
      assessed knowledge of details of cancer diagnosis and treatment among breast and
      colorectal cancer survivors. METHODS: Written surveys were completed by 480
      breast cancer survivors and 366 colorectal cancer survivors diagnosed between
      1999 and 2008 at a large cancer center in the Minneapolis, MN, area (81% response
      rate). Responses were compared with cancer registry and medical records. RESULTS:
      Forty percent of breast cancer survivors and 65% of colorectal cancer survivors
      were unable to identify their stage of disease. Seven percent of breast cancer
      survivors and 21% of colorectal cancer survivors in whom regional nodes were
      examined did not know whether they had positive nodes. Accuracy of knowledge of
      estrogen and progesterone status among breast cancer survivors was 58% and 39%,
      respectively. Of breast cancer survivors treated with doxorubicin, 43% correctly
      identified it as a drug they had received. Their accuracy of identification of
      receipt of tamoxifen or specific aromatase inhibitors was >90%. Of colorectal
      cancer survivors treated with oxaliplatin, 52% correctly identified it as a drug
      they had received. Accuracy on many items decreased with patient age.
      CONCLUSIONS: This study identifies several gaps in adult cancer survivors'
      knowledge of details of their diagnosis and treatment that have implications for
      follow-up care. IMPLICATIONS FOR CANCER SURVIVORS: Provision of written treatment
      summaries to cancer survivors could help them obtain appropriate patient-centered
      long-term follow-up care.

PMID- 21735278
TI  - [Tonsil protrusion in the case of an infraauricular mass. A rare iceberg tumor].
AB  - We report on a very rare case of iceberg tumor. A giant lipoma arising from the
      deep lobe of the parotid gland led to an infraauricular mass and tonsil
      protrusion. After appropriate imaging (ultrasound and MRI) surgical resection was
      performed. Tonsil protrusions require differential diagnostic evaluation. Apart
      from the most prevalent parotid gland tumors, like pleomorphic adenoma and
      cystadenolymphoma, one must consider rare lipomas. Malignancy (e.g. liposarcoma)
      can only be excluded by histological examination of the whole specimen.

PMID- 21735279
TI  - [Vibrotactile neurofeedback training with the Vertiguard(r)-RT-system. A placebo
      controlled double-blinded pilot study on vestibular rehabilitation].
AB  - BACKGROUND: The success of neurofeedback training for vestibular rehabilitation
      depends largely on the type of feedback signal as well as on the specific
      parameters. Ideal training should be based on the individual balance deficits in
      patients in everyday situations. The present study is therefore aimed at
      investigating the therapeutic outcome of a new vibrotactile neurofeedback system
      for the first time in a pilot study. PATIENTS AND METHODS: A total of 36 patients
      performed daily vibrotactile neurofeedback training (for 10 days) based on a sway
      analysis on the first day. The reduction of body sway and vertigo symptom scale
      (VSS) scores were calculated after the training and compared with those of the
      placebo group. RESULTS: All five patient groups (characterized by different
      vestibular disorders) which performed the training with the correct feedback
      signal showed reduced body sway and VSS score (n=30). This effect was not visible
      in the placebo group. CONCLUSIONS: Individualized vibrotactile neurofeedback
      training as presented here with the Vertiguard(r) system appeared to improve
      balance during daily activities in all patient groups investigated, but not in
      controls. Future studies should investigate the efficacy of this new method in a
      larger sample as well as its long term effects.

PMID- 21735280
TI  - [Reduced vocal cord movement and hypopharyngeal tumor].
AB  - Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the
      Western World. It belongs to the low-grade non-Hodgkin lymphomas and is
      characterized by clonal reproduction of mature small-cell non-functional B
      lymphocytes. CLL affects men somewhat more often than women and the average age
      at onset is over 50 years. In addition to regional lymph node swelling, typical
      symptoms include hepatosplenomegaly, leukocytosis and skin disorders such as
      eczema and pruritus. Manifestations in the oropharynx or hypopharynx are rare but
      should be kept in mind in the differential diagnosis.

PMID- 21735281
TI  - [Histomorphologic findings in the facial nerve after water-jet dissection of the
      parotid gland in dogs].
AB  - BACKGROUND: Initial results on the application of the water-jet in a
      parotidectomy setting in an animal study demonstrate that there are morphologic
      changes which do, and some which do not, affect the clinial function of the
      facial nerve due to the different jet sizes and operating pressures used. In a
      further study the histomorphometric data of the facial nerve dissected by the
      water-jet should be evaluated and correlated to the different sizes of jet and
      operating pressures. MATERIAL AND METHODS: In total, 102 nerves (in 14 beagles)
      which had been dissected by water-jets of different sizes and operating pressures
      were evaluated. After an observation period of 21 days, including documentation
      of the clinical function of the facial nerve, the nerves were dissected. The
      number of nerve fibers and the diameter of the different nerve fibers were then
      evaluated. RESULTS: All nerve fibers dissected with jet sizes of 120 and 150 MUm
      showed an identical cumulative frequency of fiber diameters. All nerve fibers
      dissected with a water-jet of 200 MUm showed morphologic and clinical
      abnormalities and--in terms of nerve fiber diameters--clear differences to the
      nerve fibers dissected with 120- or 150-MUm jets. Altogether, there is a decrease
      in fiber diameter along the nerve course. CONCLUSION: Our data show a shift of
      larger diameters of the nerve trunk to smaller diameters in the terminal nerve
      fibers. This phenomenon has not been described in the literature to date and is
      probably not due to the water-jet. Additionally, our data show that 22% of the
      original nerve fiber damaged by the water-jet is sufficient to preserve the
      nerve's clinical function.

PMID- 21735282
TI  - [A phenomenon called Mondegreen].
AB  - BACKGROUND: The term Mondegreens describes misperceptions as defined by "slips of
      the ear", denoting that an utterance is perceived differently to what has
      actually been said. The analysis of these misperceptions permits a deeper insight
      into speech processing in the human brain. METHOD: A selective literature
      research in PubMed has been carried out for this systematic review. RESULTS:
      Altogether, 24 publications were found addressing the issue of auditory
      misperceptions. DISCUSSION: The analysis of Mondegreens enables a
      characterization of the different levels of speech processing as well as the
      processing steps involved. The hard of hearing in particular suffer from
      misperceptions. Therefore, it should be considered whether listening programs
      could be helpful in combination with hearing aids.

PMID- 21735283
TI  - [Histomorphologic findings in the facial nerve after waterjet dissection of the
      parotid gland. Animal studies in dogs].
AB  - BACKGROUND: The postoperative facial nerve palsy is a complication after
      parotidectomy which one is afraid of. The waterjet seems to be a surgical technic
      which allows separating different tissues without destroying important structures
      like vessels and nerves. MATERIAL AND METHODS: Totally, 106 nerve preparations,
      done by the waterjet of 14 beagles, were evaluated. According to a defined
      procedure during parotidectomy by waterjet different cones and pressure were
      used. After a period time of 21 days the trunk, the frontal branch and both oral
      branches of the facial nerve of both sides were dissected. The tissue preparation
      was done using the standard technic for EM-sections. RESULTS: There are mainly
      changes due to the preparation like the reduction of nerve fibers and fibrosis
      depending which cones and pressure has been used. CONCLUSION: Therefore neither
      the size of the jet (120 or 150 MUm) nor the operating pressure of 40 to 60 or 80
      bar plays an important role for the function of the facial nerve. Damage to the
      nerve is mainly due to the preparation technic and the application time. Using
      the 200 MUm jet there is regularly facial nerve damage.

PMID- 21735284
TI  - [Child-directed speech. Does it really help language acquisition?].
AB  - BACKGROUND: Infant- or child-directed speech (CDS) defines the code used to
      communicate with infants or children, which differs from standard adult speech in
      prosody, expressions, diction and word repetition etc. METHOD: A selective
      literature search in PubMed was carried out for the purposes of this systematic
      review. RESULTS: Due to its specific advantages, child-directed speech
      facilitates the extraction and representation of relevant, meaningful sections
      from the continuous speech signal. Different speech communities use different
      variants of CDS. CDS is not only seen to be used by adults, but also by children
      communicating with younger children. However, there are speech communities that
      do not use CDS. DISCUSSION: Taking into consideration findings previously
      described in the literature, CDS appears to positively support language
      acquisition in children, but does not represent a necessary prerequisite.
      However, there are no findings in the literature to indicate that the
      linguistically reduced CDS hinders early language acquisition.

PMID- 21735285
TI  - [Extraesophageal reflux. Overview and discussion of a new method for pH
      monitoring].
AB  - BACKGROUND: Extraesophageal reflux disease often requires diagnosis and treatment
      by a phoniatry or ear, nose and throat specialist. The disease needs to be
      differentiated from gastroesophageal reflux disease. OBJECTIVE: A new
      oropharyngeal pH measuring system with a single channel probe has recently been
      introduced. The aim of this study was to compare oropharyngeal pH-metry with the
      existing diagnostic methods for extraesophageal reflux disease and to present
      initial results in our own patients. METHODS: A literature search for
      oropharyngeal pH-metry was performed in the databases NHS EED, HTA, DARE,
      Clinical trials, Cochrane reviews and Medline/PubMed. A selective literature
      search was also carried out on the problem of extraesophageal reflux disease.
      RESULTS: Evaluation scales, trial proton pump inhibitor therapy or pH-metry, for
      example, can be used to diagnose extraesophageal reflux disease. pH-metry can be
      performed using a classical two-channel pH-metry system; a new oropharyngeal pH
      measuring system has recently been introduced. This new method has been evaluated
      in initial studies for normative data and has been compared to two-channel pH
      metry. Prospective randomised studies to diagnose extraesophageal reflux disease
      with the new oropharyngeal pH-metry method are still lacking. DISCUSSION:
      Oropharyngeal pH-metry has some potential advantages compared to classical two
      channel pH-metry; however, a lot of questions remain unanswered. These will be
      discussed and illustrated with the help of a number of own patient case reports.

PMID- 21735286
TI  - [Metastasis to the paranasal sinuses from primary breast cancer].
AB  - With the symptom diplopia, in addition to an ocular cause, pathology of the
      paranasal sinuses must always be taken into consideration. A common differential
      diagnosis is an acute inflammatory process such as an orbital complication of
      acute sinusitis. We present the rare case of an initial manifestation of
      metastasis in the paranasal sinuses originating from a primary ductal carcinoma
      in situ of the breast. In our case, the metastatic manifestation and its clinical
      symptoms were the first sign of recurrence and transformation into invasive
      breast cancer.

PMID- 21735287
TI  - Maternal protein and folic acid intake during gestation does not program leptin
      transcription or serum concentration in rat progeny.
AB  - Maternal nutrition during gestation influences the development of the fetus,
      thereby determining its phenotype, including nutrient metabolism, appetite, and
      feeding behavior. The control of appetite is a very complex process and can be
      modulated by orexigenic and anorexigenic mediators such as leptin, which is
      involved in the regulation of energy homeostasis by controlling food intake and
      energy expenditure. Leptin transcription and secretion are regulated by numerous
      factors, nutrition being one of them. The present study was designed to test
      whether maternal nutrition can permanently affect leptin gene transcription and
      leptin serum concentration in rat progeny. Moreover, we analyzed whether leptin
      expression and secretion in response to high-fat postweaning feeding depends on
      the maternal diet during gestation. Pregnant rats were fed either a normal
      protein, normal folic acid diet (the AIN-93 diet); a protein-restricted, normal
      folic acid diet; a protein-restricted, folic acid-supplemented diet; or a normal
      protein, folic acid-supplemented diet. After weaning, the progeny was fed either
      the AIN-93 diet or a high-fat diet. Neither maternal nutrition nor the
      postweaning diet significantly affected Lep transcription. High-fat feeding after
      weaning was associated with higher serum leptin concentration, but the reaction
      of an organism to the fat content of the diet was not determined by maternal
      nutrition during gestation. There was no correlation between Lep mRNA level and
      serum leptin concentration. Global DNA methylation in adipose tissue was about
      30% higher in rats fed postnatally the high-fat diet (P < 0.01). Our study showed
      that the protein and folic acid content in the maternal diet had no significant
      programming effect on Lep transcription and serum leptin concentration in the
      rats.

PMID- 21735288
TI  - [Is methotrexate nephrotoxic? Dose-dependency, comorbidities and comedication].
AB  - Methotrexate (MTX) in low-doses is an important component of anti-inflammatory
      therapy of rheumatoid arthritis and other inflammatory joint diseases. In
      contrast to high-dose administration of MTX in oncology, which can lead to direct
      tubulus toxicity and subsequent renal failure, renal side-effects are a rare
      exception for low-dose MTX. The biggest problem under low-dose MTX is that an
      already limited renal function due to comorbidities or an increasing, sometimes
      clinically insufficiently monitored renal insufficiency due to comedications,
      such as non-steroidal antirheumatics (NSAR) and antibiotics, leads to a reduced
      excretion of MTX and therefore to an accumulation in serum. This is primarily
      accompanied by gastrointestinal mucositis and bone marrow depression. For this
      reason low-dose MTX should never be administered once the glomerular filtration
      rate (GFR) is less than <30 ml/min and only 50% of the original dosage should be
      administered if the GFR is between 30 and 60 ml/min.

PMID- 21735289
TI  - [Hypertrophic osteoarthropathy. Bamberger-Marie disease].
AB  - Hypertrophic osteoarthropathy (HOA) is the classical neoplastic disease in
      rheumatology characterized by a combination of digital clubbing, joint and bone
      pain, and proliferative periostitis. This combination of symptoms should initiate
      an intensive search for an underlying malignant disease usually of thoracic
      organs. Here we report the case of a patient with HOA and neuroendocrine
      carcinoma of the esophagus. Other non-malignant disorders of the lungs, heart and
      other organs should be considered in the differential diagnosis. In addition,
      rare cases of a primary hereditary form of HOA exist and the genetic background
      has recently been discovered. Thus, new insights into the pathophysiology have
      improved diagnostic and therapeutic options for this disorder.

PMID- 21735290
TI  - [Development of morbidity and mortality in patients with spondyloarthritis].
AB  - This review presents data on morbidity and mortality in patients with
      spondyloarthritis (SpA). Morbidity in patients with SpA is mainly determined by
      impairment of function and development of structural lesions. The course of
      illness in patients with ankylosing spondylitis (AS) is influenced by
      comorbidities, such as cardiovascular disease and fractures of the spine and in
      patients with psoriatic arthritis by peripheral joint manifestations. The
      mortality of patients with SpA has probably not increased but exact data are
      lacking. Approximately one third of AS patients will develop a severe disease
      state in which the mortality rate is increased by 50%.

PMID- 21735291
TI  - Force-velocity relationship for multiple kinesin motors pulling a magnetic bead.
AB  - Although the velocity of single kinesin motors against an opposing force F of 0
      10 pN is well known, the behavior of multiple kinesin motors working to overcome
      a larger load is still poorly understood. We have carried out gliding assays in
      which 3-7 Drosophila kinesin-1 motors moved a microtubule at 200-700 MUm/s
      against a 0-31 pN load at saturating [ATP]. The load F was generated by applying
      a spatially uniform magnetic field gradient to a superparamagnetic bead attached
      to the (+) end of the microtubule. When F was scaled by the average number of
      motors [Symbol: see text]n[Symbol: see text], the force-velocity relationship for
      multiple motors was similar to the force-velocity relationship for a single
      motor, supporting a minimal load-sharing model. The velocity distribution at low
      load has a single mode consistent with rapid fluctuations of n. However, against
      a load of 2.5-4.7 pN/motor, additional modes appeared at lower velocity. These
      observations support the Klumpp-Lipowsky model of multimotor transport [Proc Natl
      Acad Sci USA 102. 17284-17289 (2005)].

PMID- 21735292
TI  - MR imaging findings in 76 consecutive surgically proven cases of pericardial
      disease with CT and pathologic correlation.
AB  - To describe findings of patients with surgically confirmed pericardial disease on
      state of the art MR sequences. Retrospective review was performed for patients
      who underwent pericardiectomy and preoperative MR over a 5 year period ending in
      2009. Patients' records were reviewed to confirm the diagnosis of chronic
      recurrent pericarditis, constrictive pericarditis, or pericardial tumor. MR
      imaging findings of pericardial thickness, IVC diameter, presence or absence of
      pericardial or pleural effusion, pericardial edema, pericardial enhancement, and
      septal "bounce" were recorded. Patients with constriction had a larger IVC
      diameter (3.1 +/- 0.4 cm) than patients with recurrent pain and no constriction
      (2.0 +/- 0.4 cm). Mean pericardial thickness for the 16 patients with chronic
      recurrent pericarditis but no evidence of constriction was 4.8 +/- 2.9 mm. Mean
      pericardial thickness for patients with constriction was 9.2 +/- 7.0 cm with
      calcification, and 4.6 +/- 2.1 cm without calcification. 94% of patients with
      chronic recurrent pericarditis had gadolinium enhancement of the pericardium,
      while 76% of patients with constriction had pericardial enhancement. Septal
      "bounce" was present in 19% of chronic recurrent pericarditis cases and 86% of
      constriction cases. 5 patients had a pericardial neoplasm, 1 of which was not
      identified preoperatively. State of the art MR techniques can identify
      significant and distinct findings in patients with chronic recurrent
      pericarditis, constrictive pericarditis, and pericardial tumors.

PMID- 21735293
TI  - Evaluation of C-reactive protein, procalcitonin, tumor necrosis factor alpha,
      interleukin-6, and interleukin-8 as diagnostic parameters in sepsis-related
      fatalities.
AB  - The aims of this study were to investigate the usefulness of serum C-reactive
      protein, procalcitonin, tumor necrosis factor alpha, interleukin-6, and
      interleukin-8 as postmortem markers of sepsis and to compare C-reactive protein
      and procalcitonin values in serum, vitreous humor, and cerebrospinal fluid in a
      series of sepsis cases and control subjects, in order to determine whether these
      measurements may be employed for the postmortem diagnosis of sepsis. Two study
      groups were formed, a sepsis group (eight subjects coming from the intensive care
      unit of two university hospitals, with a clinical diagnosis of sepsis in vivo)
      and control group (ten autopsy cases admitted to two university medicolegal
      centers, deceased from natural and unnatural causes, without elements to presume
      an underlying sepsis as the cause of death). Serum C-reactive protein and
      procalcitonin concentrations were significantly different between sepsis cases
      and control cases, whereas serum tumor necrosis factor alpha, interleukin-6, and
      interleukin-8 values were not significantly different between the two groups,
      suggesting that measurement of interleukin-6, interleukin-8, and tumor necrosis
      factor alpha is non-optimal for postmortem discrimination of cases with sepsis.
      In the sepsis group, vitreous procalcitonin was detectable in seven out of eight
      cases. In the control group, vitreous procalcitonin was clearly detectable only
      in one case, which also showed an increase of all markers in serum and for which
      the cause of death was myocardial infarction associated with multi-organic
      failure. According to the results of this study, the determination of vitreous
      procalcitonin may be an alternative to the serum procalcitonin for the postmortem
      diagnosis of sepsis.

PMID- 21735294
TI  - Null alleles of the X and Y chromosomal amelogenin gene in a Chinese population.
AB  - The use of amelogenin locus typing as a gender marker incorporated in short
      tandem repeat (STR) multiplexes is a common practice in sex typing. Mutations in
      the X or Y homologue of the amelogenin gene can be misleading and result in
      serious mistakes in forensic applications and prenatal diagnosis. In these
      present studies, the amelogenin gene of 8,087 unrelated male individuals from
      Chinese Han population was genotyped with Powerplex((r))16 system. The samples
      that showed discordant results were taken for frequency calculation and further
      validated by re-amplification with different primer sets, Y-STR typing, and
      sequencing. Our results describe six amelogenin X-allele (AMELX) or amelogenin Y
      allele (AMELY) null cases in these studied subjects with an overall prevalence of
      0.074%. Further validation revealed point mutations in the amelogenin-priming
      sites associated with AMELX nulls (three cases, 0.037%) and deletions on the Y
      chromosome encompassing the AMELY and other Y-STR loci with three AMELY nulls
      (0.037%). These mutations and failure of the amplification of the AMELX and AMELY
      alleles have not been reported for the Chinese population. These and previous
      findings suggest that mutations in the amelogenin gene may result in
      amplification failure of the AMELX or AMELY allele, and an additional gender test
      for unambiguous sex determination may be needed.

PMID- 21735295
TI  - Scanner uniformity improvements for radiochromic film analysis with matt
      reflectance backing.
AB  - A simple and reproducible method for increasing desktop scanner uniformity for
      the analysis of radiochromic films is presented. Scanner uniformity, especially
      in the non-scan direction, for transmission scanning is well known to be
      problematic for radiochromic film analysis and normally corrections need to be
      applied. These corrections are dependant on scanner coordinates and dose level
      applied which complicates dosimetry procedures. This study has highlighted that
      using reflectance scanning in combination with a matt, white backing material
      instead of the conventional gloss scanner finish, substantial increases in the
      scanner uniformity can be achieved within 90% of the scanning area. Uniformity
      within +/-1% over the scanning area for our epsonV700 scanner tested was found.
      This is compared to within +/-3% for reflection scanning with the gloss backing
      material and within +/-4% for transmission scanning. The matt backing material
      used was simply 5 layers of standard quality white printing paper (80 g/m(2)). It
      was found that 5 layers was the optimal result for backing material however most
      of the improvements were seen with a minimum of 3 layers. Above 5 layers, no
      extra benefit was seen. This may eliminate the need to perform scanner
      corrections for position on the desktop scanners for radiochromic film dosimetry.

PMID- 21735296
TI  - Spinal projections from the presumptive midbrain locomotor region in the mouse.
AB  - The mesencephalic locomotor region (MLR) plays an important role in the control
      of locomotion, but there is ongoing debate about the anatomy of its connections
      with the spinal cord. In this study, we have examined the spinal projections of
      the mouse precuneiform nucleus (PrCnF), which lies within the boundaries of the
      presumptive MLR. We used both retrograde and anterograde labeling techniques.
      Small clusters of labeled neurons were seen in the medial portion of the PrCnF
      following fluoro-gold injections in the upper cervical spinal cord. Fewer labeled
      neurons were seen in the PrCnF after upper thoracic injections. Following the
      injection of anterograde tracer (biotinylated dextran amine) into the PrCnF,
      labeled fibers were clearly observed in the spinal cord. These fibers traveled in
      the ventral and lateral funiculi, and terminated mainly in the medial portions of
      laminae 7, 8, and 9, as well as area 10, with an ipsilateral predominance. Our
      observations indicate that projections from the PrCnF to the spinal cord may
      provide an anatomical substrate for the role of the MLR in locomotion.

PMID- 21735297
TI  - Lower catheter-related bloodstream infection in arterial than in venous femoral
      catheter.
AB  - In previous studies no differences were found in catheter-related bloodstream
      infection (CRBSI) between arterial and venous catheters. However, the
      distribution of each venous and arterial site could influence the results as in
      some studies a higher CRBSI incidence in venous and arterial femoral accesses has
      been found than in other venous and arterial accesses. Possibly, to eliminate
      this confounding, it might be more appropriate to compare the CRBSI incidence
      between arterial and venous catheters in the same site as the femoral access.
      Thus, the objective of this study was to compare the incidence of CRBSI between
      618 arterial and 288 venous femoral accesses. We found higher CRBSI incidence in
      venous than in arterial femoral catheters (8.34 vs 1.92 CRBSI episodes/1,000
      catheter-days; P < 0.001). Exact logistic regression analysis showed that venous
      femoral catheters had a higher risk of CRBSI than arterial femoral catheters (OR
      = 1.02; 95%CI =1.01-infinite; P < 0.001) controlled by APACHE-II score and
      duration of the catheter. The novel finding of our study is that the risk of
      CRBSI was higher in venous than in arterial femoral catheters. Thus, special
      approaches to prevent CRBSI might play a more important role in venous than in
      arterial catheters.

PMID- 21735298
TI  - Noninvasive positive pressure ventilation in the management of post-thyroidectomy
      tracheomalacia.
AB  - BACKGROUND: Post-thyroidectomy tracheomalacia is a rare but complicated problem.
      It has often been treated with tracheostomy or prolonged endotracheal intubation.
      However, noninvasive positive pressure ventilation (NPPV) has been successfully
      employed with increasing frequency in patients with respiratory failure from
      other causes. In the present study we describe the use of NPPV in the management
      of respiratory distress in patients with post-thyroidectomy tracheomalacia.
      METHODS: All 606 patients who underwent thyroidectomy in Chung Gung Memorial
      Hospital - Kaohsiung Medical Center, Taiwan, from January 2009 to August 2010
      were reviewed. If tracheomalacia was diagnosed intraoperatively, the patients
      were left intubated and taken to the intensive care unit (ICU) (n = 5). If
      tracheomalacia was diagnosed in the recovery room (stridor and airway compromise
      not from other causes), the patient was reintubated promptly and taken to the ICU
      (n = 4). When subsequently re-extubated in the ICU (24-72 h later), NPPV was used
      to treat recurrent stridor and airway compromise. RESULTS: A total of nine
      patients (1.5 %) were diagnosed with post-thyroidectomy tracheomalacia, five
      intraoperatively and four postoperatively. The patients were intubated with an
      endotracheal tube and then taken to the ICU. After early re-extubation in the
      ICU, three of the patients with intraoperatively diagnosed tracheomalacia were
      found not to have respiratory problems, whereas the other six patients developed
      stridor and airway compromise, which resolved immediately with the initiation of
      NPPV. Hemoglobin oxygen saturation on pulse oximetry was also elevated. No
      further respiratory support was required and no complications occurred in these
      patients. CONCLUSIONS: Noninvasive positive pressure ventilation is effective and
      appears safe in the management of stridor and airway compromise following early
      extubation in patients with post-thyroidectomy tracheomalacia.

PMID- 21735299
TI  - Heavy metal in children's tooth enamel: related to autism and disruptive
      behaviors?
AB  - To examine possible links between neurotoxicant exposure and neuropsychological
      disorders and child behavior, relative concentrations of lead, mercury, and
      manganese were examined in prenatal and postnatal enamel regions of deciduous
      teeth from children with Autism Spectrum Disorders (ASDs), high levels of
      disruptive behavior (HDB), and typically developing (TD) children. Using laser
      ablation inductively coupled plasma mass spectrometry, we found no significant
      differences in levels of these neurotoxicants for children with ASDs compared
      with TD children, but there was marginal significance indicating that children
      with ASDs have lower manganese levels. No significant differences emerged between
      children with HDB and TD children. The current findings challenge the notion that
      perinatal heavy metal exposure is a major contributor to the development of ASDs
      and HDB.

PMID- 21735300
TI  - Management of warfarin in children with heart disease.

PMID- 21735301
TI  - Physical activity and sedentary behavior across the lifespan.

PMID- 21735302
TI  - Mental health provider perspectives regarding integrated medical care for
      patients with serious mental illness.
AB  - Integrated care for medical conditions is essential for persons with serious
      mental illness (SMI). This qualitative study describes mental health provider
      perspectives regarding barriers and facilitators of integrated care for patients
      with SMI. We interviewed providers from a national sample of Veterans Health
      Administration facilities that scored in the top or bottom percentile in medical
      care quality. Providers from high-performing sites reported substantial in-person
      contacts with general medical providers, while providers from low-performing
      sites reported stigma and limited communication with medical providers as major
      concerns. Interventions to improve mental health and medical provider
      communication may facilitate integrated care for persons with SMI.

PMID- 21735304
TI  - Porcine carcass phantom for ultrasound imaging and hands-on practice in needle
      insertion in the thoracic paravertebral space.

PMID- 21735303
TI  - Sensing the cardiac environment: exploiting cues for regeneration.
AB  - Recent pre-clinical and clinical studies indicate that certain exogenous stem
      cells and biomaterials can preserve cardiac tissue after myocardial infarction.
      Regarding stem cells, a growing body of data suggests that the short-term
      positive outcomes are mainly attributed to paracrine signaling mechanisms. The
      release of such factors is due to the cell's ability to sense cardiac
      environmentally derived cues, though the exact feedback loops are still poorly
      understood. However, given the limited engraftment and survival of transplanted
      cells in the ischemic environment, the long-term clinical benefits of these
      therapies have not yet been realized. To overcome this, the long-term controlled
      delivery of bioactive factors using biomaterials is a promising approach. A major
      challenge has been the ability to develop timely and spatially controlled
      gradients of different cues, pivotal for the development and regeneration of
      tissues. In addition, given the complexity of the remodeling process after
      myocardial infarction, multiple factors may be required at distinct disease
      stages to maximize therapeutic outcomes. Therefore, novel smart materials that
      can sense the surrounding environment and generate cues through on demand
      mechanisms will be of major importance in the translation of these promising
      advanced therapies. This article reviews how the cardiac environment can mediate
      the release profiles of bioactive cues from cells and biomaterials and how the
      controlled delivery impacts heart regeneration.

PMID- 21735305
TI  - The impact of college education on fertility: evidence for heterogeneous effects.
AB  - As college-going among women has increased, more women are going to college from
      backgrounds that previously would have precluded their attendance and completion.
      This affords us the opportunity and motivation to look at the effects of college
      on fertility across a range of social backgrounds and levels of early
      achievement. Despite a substantial literature on the effects of education on
      women's fertility, researchers have not assessed variation in effects by
      selection into college. With data on U.S. women from the National Longitudinal
      Survey of Youth 1979, we examine effects of timely college attendance and
      completion on women's fertility by the propensity to attend and complete college
      using multilevel Poisson and discrete-time event-history models. Disaggregating
      the effects of college by propensity score strata, we find that the fertility
      decreasing college effect is concentrated among women from comparatively
      disadvantaged social backgrounds and low levels of early achievement. The effects
      of college on fertility attenuate as we observe women from backgrounds that are
      more predictive of college attendance and completion.

PMID- 21735306
TI  - Measurement properties of disease-specific questionnaires in patients with neck
      pain: a systematic review.
AB  - PURPOSE: To critically appraise and compare the measurement properties of the
      original versions of neck-specific questionnaires. METHODS: Bibliographic
      databases were searched for articles concerning the development or evaluation of
      the measurement properties of an original version of a self-reported
      questionnaire, evaluating pain and/or disability, which was specifically
      developed or adapted for patients with neck pain. The methodological quality of
      the selected studies and the results of the measurement properties were
      critically appraised and rated using a checklist, specifically designed for
      evaluating studies on measurement properties. RESULTS: The search strategy
      resulted in a total of 3,641 unique hits, of which 25 articles, evaluating 8
      different questionnaires, were included in our study. The Neck Disability Index
      is the most frequently evaluated questionnaire and shows positive results for
      internal consistency, content validity, structural validity, hypothesis testing,
      and responsiveness, but a negative result for reliability. The other
      questionnaires show positive results, but the evidence for each measurement
      property is mostly limited, and at least 50% of the information on measurement
      properties per questionnaire is lacking. CONCLUSIONS: Our findings imply that
      studies of high methodological quality are needed to properly assess the
      measurement properties of the currently available questionnaires. Until high
      quality studies are available, we recommend using these questionnaires with
      caution. There is no need for the development of new neck-specific questionnaires
      until the current questionnaires have been adequately assessed.

PMID- 21735307
TI  - Why perform a quality or quality-of-life assessment?
AB  - The purpose of this article is to prompt quality-of-life researchers to
      periodically ask themselves why they are doing what they are doing. I will give
      you my answer to this question, but also briefly review the historic events that
      lead to the development of the field. Examining this history should teach each of
      us that the field evolved from the application of a operations research
      perspective to the medical care system. As such, more attention should be given
      to the quality control potential of quality-of-life assessments. I suggest two
      approaches to this quality control task; the prevention of adverse events and the
      enhancement of the qualitative status of ill persons.

PMID- 21735308
TI  - Double negatives do not make a positive editorial experience.

PMID- 21735309
TI  - Factors related to seizure in tramadol poisoning and its blood concentration.
AB  - This study examines the relation between seizure and plasma tramadol
      concentration in patients with tramadol poisoning, as a novel centrally acting
      analgesic used for the treatment of mild to severe pain. All patients admitted
      with a history of tramadol overdose accompanied by unconsciousness or seizures
      referred to Baharloo Hospital Poison Center, Tehran, Iran from March 2008 to
      March 2009 were included. Demographic information, clinical findings, and blood
      tramadol concentrations were studied. There were 401 patients with a history of
      tramadol overdose; 121 (30.2%) with a history of seizure and 14 (3.5%) with a
      history of unconsciousness were included. Most of overdoses involved men (83%).
      The mean age was 22.9 years (range, 14-50 years). Intentional overdose was the
      most common mode of poisoning (51.9%). The mean dose ingested was 1,511 mg (SD,
      1,353; range, 200-7,000). Mean back-extrapolated tramadol blood concentrations
      were 3,843 ng/mL (3,715; 269-20,049). Back-extrapolated blood concentrations were
      correlated with dose (r = 0.313; P < 0.001) as well as blood concentration levels
      (r = 0.801; P < 0.001). Seizure was significantly correlated to higher reported
      dose (P < 0.001) and tramadol only to overdose (P < 0.001). However, it was
      neither related to higher tramadol blood concentrations, nor related to time
      elapsed, age, sex, history of addiction, and observed Glasgow Coma Scale of
      patients. Most patients experienced just one seizure (76%). The tramadol-induced
      seizure is dose dependent. Although higher doses of tramadol was related to
      higher blood concentration, blood tramadol concentrations was not associated with
      seizure.

PMID- 21735310
TI  - Cardiotoxicity and serotonin syndrome complicating a milnacipran overdose.
AB  - Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor,
      recently approved for use in the USA for treatment of fibromyalgia. This case
      report describes a 59-year-old woman who ingested 3,000 mg of milnacipran in a
      suicide attempt. Following the ingestion, she became obtunded and developed
      autonomic instability. She required mechanical ventilation, treatment for
      hypertension, and then ultimately vasopressor support for refractory hypotension.
      In addition, she developed a transient, acute cardiac dysfunction with global
      hypokinesis and an ejection fraction of 30%. Resolution of the cardiac
      dysfunction was documented on repeat echocardiogram 2 days after the initial
      study. This was confirmed by cardiac catheterization performed 4 days after the
      acute ingestion in which coronary arteriogram was normal and left ventricular
      ejection fraction was 70%. Acute overdose was confirmed by quantification of
      plasma milnacipran concentration of 8,400 ng/mL obtained 5 h post-ingestion. To
      our knowledge, this represents the first case of cardiac toxicity complicating a
      milnacipran overdose in the medical literature.

PMID- 21735311
TI  - Acute thallium poisoning: series of ten cases.

PMID- 21735312
TI  - Multiple-look effects on temporal discrimination within sound sequences.
AB  - The multiple-look notion holds that the difference limen (DL) decreases with
      multiple observations. We investigated this notion for temporal discrimination in
      isochronous sound sequences. In Experiment 1, we established a multiple-look
      effect when sequences comprised nine standard time intervals (S) followed by an
      increasing number of comparison time intervals (C), but no multiple-look effect
      when one trailing C interval was preceded by an increasing number of S intervals.
      In Experiment 2, we extended the design. There were four sequential conditions:
      (a) 9 leading S intervals followed by 1, 2, ..., or 9 C-intervals; (b) 9 leading
      C intervals followed by 1, 2, ..., or 9 S intervals; (c) 9 trailing C-intervals
      preceded by 1, 2, ..., or 9 S-intervals; and (d) 9 trailing S-intervals preceded
      by 1, 2, ..., or 9 C-intervals. Both the interval accretions before and after the
      tempo change caused multiple-look effects, irrespective of the time order of S
      and C. Complete deconfounding of the number of intervals before and after the
      tempo change was accomplished in Experiment 3. The multiple-look effect of
      interval accretion before the tempo change was twice as big as that after the
      tempo change. The diminishing returns relation between the DL and interval
      accretion could be described well by a reciprocal function.

PMID- 21735313
TI  - The underestimation of egocentric distance: evidence from frontal matching tasks.
AB  - There is controversy over the existence, nature, and cause of error in egocentric
      distance judgments. One proposal is that the systematic biases often found in
      explicit judgments of egocentric distance along the ground may be related to
      recently observed biases in the perceived declination of gaze (Durgin & Li,
      Attention, Perception, & Psychophysics, in press), To measure perceived
      egocentric distance nonverbally, observers in a field were asked to position
      themselves so that their distance from one of two experimenters was equal to the
      frontal distance between the experimenters. Observers placed themselves too far
      away, consistent with egocentric distance underestimation. A similar experiment
      was conducted with vertical frontal extents. Both experiments were replicated in
      panoramic virtual reality. Perceived egocentric distance was quantitatively
      consistent with angular bias in perceived gaze declination (1.5 gain). Finally,
      an exocentric distance-matching task was contrasted with a variant of the
      egocentric matching task. The egocentric matching data approximate a constant
      compression of perceived egocentric distance with a power function exponent of
      nearly 1; exocentric matches had an exponent of about 0.67. The divergent pattern
      between egocentric and exocentric matches suggests that they depend on different
      visual cues.

PMID- 21735314
TI  - Interval bias in 2AFC detection tasks: sorting out the artifacts.
AB  - Proportion correct in two-alternative forced choice (2AFC) detection tasks often
      varies when the stimulus is presented in the first or in the second interval.
      Reanalysis of published data reveals that these order effects (or interval bias)
      are strong and prevalent, refuting the standard difference model of signal
      detection theory. Order effects are commonly regarded as evidence that observers
      use an off-center criterion under the difference model with bias. We consider an
      alternative difference model with indecision whereby observers are occasionally
      undecided and guess with some bias toward one of the response options. Whether or
      not the data show order effects, the two models fit 2AFC data indistinguishably,
      but they yield meaningfully different estimates of sensory parameters. Under
      indeterminacy as to which model governs 2AFC performance, parameter estimates are
      suspect and potentially misleading. The indeterminacy can be circumvented by
      modifying the response format so that observers can express indecision when
      needed. Reanalysis of published data collected in this way lends support to the
      indecision model. We illustrate alternative approaches to fitting psychometric
      functions under the indecision model and discuss designs for 2AFC experiments
      that improve the accuracy of parameter estimates, whether or not order effects
      are apparent in the data.

PMID- 21735316
TI  - Serum apolipoprotein C-III is independently associated with chronic hepatitis C
      infection and advanced fibrosis.
AB  - BACKGROUND: The hepatitis C virus (HCV) is known to disrupt lipid metabolism,
      making serum lipoprotein levels good candidates to explore as markers of HCV
      disease progression. Assessment of the major apolipoproteins (Apo) and their
      relationship to hepatic fibrosis remain largely unexplored. METHODS: We compared
      the levels of total cholesterol, triglycerides, low-density lipoprotein
      cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and Apo A
      I, -B, -C-III, and -E between patients with cleared versus active infection (n =
      83), and between those chronically infected patients (n = 216) with advanced
      versus mild-moderate hepatic fibrosis (METAVIR stage F3-4 vs. F0-2) using
      multiple logistic regression. RESULTS: Apo C-III levels were 25% higher in
      subjects with cleared infection versus those with active infection (p = 0.009).
      Low levels of Apo C-III (p = 1.3 * 10(-5)), Apo A-I (p = 2.9 * 10(-5)), total
      cholesterol (p = 5.0 * 10(-4)), LDL-C (p = 0.005), and HDL-C (p = 2.0 * 10(-4))
      were associated with advanced fibrosis in univariate analyses. Multivariable
      analysis revealed Apo C-III as the most significant factor associated with
      advanced fibrosis (p = 0.0004), followed by age (p = 0.013) and Apo A-I (p =
      0.022). Inclusion of both Apo C-III and Apo A-I in a model to predict advanced
      fibrosis improved the area under the receiver operator curve only modestly.
      CONCLUSIONS: Relative to other lipoproteins, low serum Apo C-III levels are the
      most strongly associated with chronic versus cleared infection and decline with
      increasing severity of hepatic fibrosis. Apo C-III deserves further attention as
      a possible marker of HCV disease progression.

PMID- 21735315
TI  - Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease
      progression and neuropathogenesis.
AB  - About one third of acquired immunodeficiency syndrome cases in the USA have been
      attributed to the use of injected addictive drugs, frequently involving opioids
      like heroin and morphine, establishing them as significant predisposing risk
      factors for contracting human immunodeficiency virus type 1 (HIV-1). Accumulating
      evidence from in vitro and in vivo experimental systems indicates that opioids
      act in concert with HIV-1 proteins to exacerbate dysregulation of neural and
      immune cell function and survival through diverse molecular mechanisms. In
      contrast, the impact of opioid exposure and withdrawal on the viral life cycle
      and HIV-1 disease progression itself is unclear, with conflicting reports
      emerging from the simian immunodeficiency virus and simian-human immunodeficiency
      virus infection models. However, these studies suggest a potential role of
      opioids in elevated viral production. Because human microglia, astrocytes, CD4+ T
      lymphocytes, and monocyte-derived macrophages express opioid receptors, it is
      likely that intracellular signaling events triggered by morphine facilitate
      enhancement of HIV-1 infection in these target cell populations. This review
      highlights the biochemical changes that accompany prolonged exposure to and
      withdrawal from morphine that synergize with HIV-1 proteins to disrupt normal
      cellular physiological functions especially within the central nervous system.
      More importantly, it collates evidence from epidemiological studies, animal
      models, and heterologous cell systems to propose a mechanistic link between such
      physiological adaptations and direct modulation of HIV-1 production.
      Understanding the opioid-HIV-1 interface at the molecular level is vitally
      important in designing better treatment strategies for HIV-1-infected patients
      who abuse opioids.

PMID- 21735317
TI  - Exercise pre-conditioning reduces brain inflammation and protects against
      toxicity induced by traumatic brain injury: behavioral and neurochemical
      approach.
AB  - Although the favorable effects of physical exercise in neurorehabilitation after
      traumatic brain injury (TBI) are well known, detailed pathologic and functional
      alterations exerted by previous physical exercise on post-traumatic cerebral
      inflammation have been limited. In the present study, it is showed that fluid
      percussion brain injury (FPI) induced motor function impairment, followed by
      increased plasma fluorescein extravasation and cerebral inflammation
      characterized by interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha)
      increase, and decreased IL-10. In addition, myeloperoxidase (MPO) increase and
      Na+,K+-ATPase activity inhibition after FPI suggest that the opening of blood
      brain barrier (BBB) followed by neurtrophils infiltration and cerebral
      inflammation may contribute to the failure of selected targets leading to
      secondary damage. In fact, Pearson's correlation analysis revealed strong
      correlation of MPO activity increase with Na+,K+-ATPase activity inhibition in
      sedentary rats. Statistical analysis also revealed that previous running exercise
      (4 weeks) protected against FPI-induced motor function impairment and fluorescein
      extravasation. Previous physical training also induced IL-10 increase per se and
      protected against cerebral IL-1beta, and TNF-alpha increase and IL-10 decrease
      induced by FPI. This protocol of physical training was effective against MPO
      activity increase and Na+,K+-ATPase activity inhibition after FPI. The present
      protection correlated with MPO activity decrease suggests that the alteration of
      cerebral inflammatory status profile elicited by previous physical training
      reduces initial damage and limits long-term secondary degeneration after TBI.
      This prophylactic effect may facilitate functional recovery in patients suffering
      from brain injury induced by TBI.

PMID- 21735319
TI  - How important is the recommended slow cuff pressure deflation rate for blood
      pressure measurement?
AB  - Cuff pressure deflation rate influences blood pressure (BP) measurement. However,
      there is little quantitative clinical evidence on its effect. Oscillometric
      pulses recorded from 75 subjects at the recommended deflation rate of 2-3 mmHg
      per second were analyzed. Some pulses were removed to realize six faster rates (2
      7 times faster than the original). Systolic, diastolic, and mean arterial blood
      pressures (SBP, DBP, MAP) were determined from the original and six reconstructed
      oscillometric waveforms. Manual measurement was based on the appearance of
      oscillometric pulse peaks, and automatic measurement on two model envelopes
      (linear and polynomial) fitted to the sequence of oscillometric pulse amplitudes.
      The effects of deflation rate on BP determination and within-subject BP
      variability were analyzed. For SBP and DBP determined from the manual
      measurement, different deflation rates resulted in significant changes (both p <
      0.001). However, for SBP, DBP, and MAP determined from the automatic linear and
      polynomial model techniques, there was no deflation rate effect (all p > 0.3).
      Faster deflation increased the within-subject BP variability (all p < 0.001). In
      conclusion, for the manual technique accurate BP measurement could be achieved
      only with the recommended slow deflation rate, and for the automatic model-based
      techniques, the deflation rate had little effect.

PMID- 21735320
TI  - Skull flexure as a contributing factor in the mechanism of injury in the rat when
      exposed to a shock wave.
AB  - The manner in which energy from an explosion is transmitted into the brain is
      currently a highly debated topic within the blast injury community. This study
      was conducted to investigate the injury biomechanics causing blast-related
      neurotrauma in the rat. Biomechanical responses of the rat head under shock wave
      loading were measured using strain gauges on the skull surface and a fiber optic
      pressure sensor placed within the cortex. MicroCT imaging techniques were applied
      to quantify skull bone thickness. The strain gauge results indicated that the
      response of the rat skull is dependent on the intensity of the incident shock
      wave; greater intensity shock waves cause greater deflections of the skull. The
      intracranial pressure (ICP) sensors indicated that the peak pressure developed
      within the brain was greater than the peak side-on external pressure and
      correlated with surface strain. The bone plates between the lambda, bregma, and
      midline sutures are probable regions for the greatest flexure to occur. The data
      provides evidence that skull flexure is a likely candidate for the development of
      ICP gradients within the rat brain. This dependency of transmitted stress on
      particular skull dynamics for a given species should be considered by those
      investigating blast-related neurotrauma using animal models.

PMID- 21735318
TI  - Dopamine and paraquat enhance alpha-synuclein-induced alterations in membrane
      conductance.
AB  - We have previously demonstrated that alpha-synuclein overexpression increases the
      membrane conductance of dopaminergic-like cells. Although alpha-synuclein is
      thought to play a central role in the pathogenesis of several neurodegenerative
      diseases including Parkinson's disease, multiple system atrophy, and diffuse Lewy
      body disease, the mechanism of action is not completely understood. In this
      study, we sought to determine whether multiple factors act together with alpha
      synuclein to engender cell vulnerability through an augmentation of membrane
      conductance. In this article, we employed a cell model that mimics dopaminergic
      neurons coupled with alpha-synuclein overexpression and oxidative stressors. We
      demonstrate an enhancement of alpha-synuclein-induced toxicity in the presence of
      combined treatment with dopamine and paraquat, two molecules known to incite
      oxidative stress. In addition, we show that combined dopamine and paraquat
      treatment increases the expression of heme oxygenase-1, an antioxidant response
      protein. Finally, we demonstrate for the first time that combined treatment of
      dopaminergic cells with paraquat and dopamine enhances alpha-synuclein-induced
      leak channel properties resulting in increased membrane conductance. Importantly,
      these increases are most robust when both paraquat and dopamine are present
      suggesting the need for multiple oxidative insults to augment alpha-synuclein
      induced disruption of membrane integrity.

PMID- 21735321
TI  - Religiosity and sexual involvement within adolescent romantic couples.
AB  - The impact of religiosity in adolescent romantic partnerships on sexual behavior
      was assessed. Data were obtained from the National Longitudinal Study of
      Adolescent Health reciprocated couples database using religious- and relationship
      oriented variables to predict sexual involvement in 374 couples (748
      participants). We found that individual- and couple-based religiosity impacted
      sexual behavior. These findings provide evidence for dyad religiosity as a
      component involved in the expression of sexual behavior in romantic
      relationships. The current results highlight the importance of incorporating a
      broad social perspective in order to understand the expression of adolescent
      sexual behavior. 

PMID- 21735322
TI  - Fast-track laparoscopic gastric bypass surgery: outcomes and lessons from a
      bariatric surgery service in the United Kingdom.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a potentially
      complicated surgery with significant hospitalisation, especially during the
      learning curve. There are inadequate data on fast-track LRYGB in relation to
      learning curve. This study highlights the outcomes of a fast-track LRYGB service.
      METHODS: This observational study examined the perioperative outcome data of 406
      consecutive LRYGB patients over a 4-year period. Perioperative outcome data were
      analysed and compared between severe obesity, morbid obesity and super obesity
      groups. RESULTS: Mean BMI was 48.6 +/- 8.3, mean age was 42 years and male to
      female ratio was 1:4. About 4% of patients had concurrent ventral hernia repair.
      Median duration of combined LRYGB and ventral hernia repair was 115 min, compared
      to 95 min for LRYGB alone (p = 0.09). Intraoperative complication rate was 0.5%.
      Postoperative complications occurred in 3.4% of patients with 60% within 24 h.
      The complication rate per obesity group was <7% and similar between groups (p =
      0.4). There was no perioperative mortality. More super obese patients received
      postoperative intensive care compared to others (p = 0.001). Mean length of
      hospital stay was similar between obesity groups and decreased from 2 to 1 day
      over 2 years. There was a learning curve of 109 cases over 2 years. CONCLUSION:
      LRYGB is a safe technique of bariatric surgery with low risk of perioperative
      complications. Establishing a fast-track LRYGB service requires a learning curve
      of 100 cases, and a good indicator is length of hospital stay, which decreases as
      the service matures. Most LRYGB patients can be safely discharged by 24 h.

PMID- 21735323
TI  - Preservation of the pyloric ring has little value in surgery for pancreatic head
      cancer: a comparative study comparing three surgical procedures.
AB  - BACKGROUND: Pylorus-preserving pancreatoduodenectomy (PPPD) has replaced
      conventional pancreatoduodenectomy with a distal gastrectomy (cPD) as the most
      commonly performed procedure. However, there has been no evidence from
      prospective studies to indicate the overwhelming superiority of PPPD over cPD. A
      recent report revealed that resection of the pyloric ring reduced the incidence
      of delayed gastric emptying (DGE) in a randomized controlled trial. METHODS: In
      158 patients with pancreatic head cancer, the perioperative outcomes and long
      term nutritional consequences were retrospectively compared among three types of
      pancreatoduodenectomy: cPD; PPPD; and subtotal stomach-preserving
      pancreatoduodenectomy (SSPPD), in which the pyloric ring and duodenum were
      removed and more than 90% of the stomach was preserved. RESULTS: The incidence of
      DGE was significantly higher in the PPPD group than in the cPD and SSPPD groups
      (27.3 vs. 5.8 and 5.4%, respectively; P = 0.0012). The serum albumin
      concentration and total lymphocyte count at 1 year postoperatively were
      significantly higher in the SSPPD group than in the PPPD group (P = 0.0303 and P
      = 0.0203, respectively). The patients in the SSPPD group showed longer survival
      times than the patients in the cPD and PPPD groups (median survival times, 21.3,
      17.1, and 17.7 months, respectively), although the differences did not reach
      statistical significance. CONCLUSIONS: Our results suggest that preservation of
      the pyloric ring without vagal innervation has little significance, and that
      SSPPD with better perioperative and long-term outcomes is more suitable as a
      standard procedure for patients with pancreatic head cancer.

PMID- 21735324
TI  - Impact of radiation therapy sequence on survival among patients with resected
      pancreatic head ductal carcinoma.
AB  - BACKGROUND: Neoadjuvant therapy for pancreatic cancer is increasingly studied,
      but no randomized data is available to address its clinical utility. The purpose
      of this study is to compare the impact of the sequencing of radiation therapy and
      surgery on overall survival (OS) of patients, who received both
      pancreaticoduodenectomy and radiation therapy. METHODS: Surveillance,
      Epidemiology, and End Results data on pancreatic head carcinoma patients
      diagnosed between 1991 and 2007 was used. OS of patients receiving neoadjuvant
      (nRT, n=111) versus adjuvant radiation therapy (aRT, n=1839) was the primary end
      point. Excluded were cases in which resection or radiation therapy were omitted.
      RESULTS: The groups were comparable with respect to age (63+/-9 vs. 62+/-10years,
      P=0.490) and gender distribution. Median OS was similar in the nRT and aRT groups
      (19 vs. 20 months, P=0.688). On multivariate analysis, nodal status (hazard ratio
      [HR] 1.35, P<0.001) and age (HR 1.01/year, P<0.001) were predictive of OS, but RT
      sequence was not. CONCLUSIONS: Survival of patients undergoing
      pancreaticoduodenectomy for pancreatic head carcinoma does not seem to be
      affected by sequence of perioperative radiation therapy. This finding would imply
      that prospective studies comparing nRT to aRT is warranted to examine potential
      clinical benefits of nRT and can be carried out without compromising patient
      outcome.

PMID- 21735325
TI  - Epithelioid angiosarcoma with metastatic disease after endovascular therapy of
      abdominal aortic aneurysm.
AB  - Malignancies of the aortic wall represent a rare condition, and only a few
      reports have covered cases of sarcomas arising at the site of a prosthesis made
      of Dacron. A coincidence with endovascular repair has only been reported in one
      case to date. We report a patient with epithelioid angiosarcoma and metastatic
      disease, which was found in an aneurysmal sac after endovascular aortic repair
      for abdominal aortic aneurysm.

PMID- 21735326
TI  - Comparative evaluation of laparoscopic liver resection for posterosuperior and
      anterolateral segments.
AB  - BACKGROUND: Totally laparoscopic liver resection of lesions located in the
      posterosuperior segments is reported to be technically challenging. This study
      aimed to define whether these technical difficulties affect the surgical outcome.
      METHODS: A total of 220 patients underwent laparoscopic liver resection during
      244 procedures from August 1998 to December 2010. The patients who underwent
      primary minor single liver resection for malignant tumors affecting either
      posterosuperior segments 1, 7, 8, and, 4a (group 1) or anterolateral segments 2,
      3, 5, 6, and 4b (group 2) were included in the study. Seventy-five procedures
      found to be eligible for the study, including 28 patients in group 1 and 47
      patients in group 2. Intraoperative unfavorable incidents were graded on the
      basis of the Satava approach and postoperative complications were graded in
      agreement with the Accordion classification. RESULTS: The operative time (median,
      127 min) and blood loss (median, 200 ml) were equivalent in the two groups. The
      rates for blood transfusions and intraoperative accidents did not differ
      statistically between the groups. A tumor-free margin resection was achieved in
      94.7% of the procedures, equivalently in both groups. The postoperative course
      was similar in the two groups. Postoperative complications developed in 2 cases
      (7.1%) in group 1 and 2 cases (4.3%) in group 2 (p = 0.626). The median hospital
      stay was 2 days in both groups. CONCLUSIONS: Laparoscopic liver resection for
      lesions located in posterosuperior segments represents certain technical
      challenges. However, appropriate adjustment of surgical techniques and optimal
      patient positioning enables the laparoscopic technique to provide safe and
      effective parenchyma-sparing resections for lesions located in both
      posterosuperior and anterolateral segments.

PMID- 21735327
TI  - Laparoscopy as the initial approach for epiphrenic diverticula.
AB  - BACKGROUND: Most epiphrenic diverticula traditionally have been approached
      through a left thoracotomy. Because laparoscopy provides excellent exposure to
      the distal esophagus and decreases the morbidity of thoracoscopy or thoracotomy,
      we have used it preferentially since 1997 and routinely since 2001. This study
      describes our experience with this approach. METHODS: From 1997 to 2008, 23
      patients underwent surgery for epiphrenic diverticula at the University of
      Washington so that all patients are >=2 years out. Our initial approach was via
      laparoscopy in 19 patients, VATS in 2, and open thoracotomy in 2. Details of the
      operation and postoperative course were recorded in our database. The patients
      were contacted by one of the investigators regarding current symptoms. RESULTS:
      The median age was 57 (range 23-83) years. The medium follow-up was 45 months.
      Eighteen patients had esophageal manometry at our institution; 12 of them were
      abnormal (66.67%). The median diameter of diverticula was 4 (range 2-10) cm. From
      the 19 patients approached by laparoscopy, there was one conversion to open
      thoracotomy in a patient with an associated leiomyoma. Both patients approached
      by VATS were converted to thoracotomy. Patients initially approached by
      laparoscopy had a median length of stay of 3 days. There was one contained
      esophageal leak. One patient died within 30 days from complications of the
      operation. Ninety-two percent of patients reported improvement of their dysphagia
      and 77% improvement of regurgitation. None of the patients developed recurrent
      diverticula. Eighty-five percent of the patients rated the results of the
      operation as good or excellent. CONCLUSIONS: Most epiphrenic diverticula can be
      treated successfully by using a laparoscopic approach. Morbidity and conversion
      rates are low and symptom control is excellent.

PMID- 21735328
TI  - No evidence for an association between genetic variation at the MMP2 and MMP9
      loci and aneurysmal subarachnoid haemorrhage.

PMID- 21735329
TI  - Extensive performance on the antisaccade task does not lead to negative transfer.
AB  - Executive-control processes regulate thoughts, emotions, actions, and behaviors
      that are critical for everyday functioning. Recently, researchers have suggested
      that these processes can be flexibly modified by tasks that require executive
      control. Specifically, it has been argued that executive-control tasks can
      deplete these executive-control processes, which can in turn lead to negative
      transfer on subsequent task performance. Importantly, the degrees of malleability
      in executive-control processes and transfer to different tasks are of ongoing
      debate. The present study critically examined the hypothesis that executive
      control processes can be exerted and whether or not this exertion would
      negatively transfer to performance on various subsequent tasks. Across a series
      of experiments, negative transfer effects from extensive performance on the
      antisaccade task were not found. Traditional hypothesis testing and Bayes factor
      computations were used to validate these findings. Collectively, the present
      results put in question the use of the antisaccade task to observe both near and
      far negative transfer from using executive-control processes.

PMID- 21735330
TI  - Positional effects in the lexical retuning of speech perception.
AB  - Listeners use lexical knowledge to adjust to speakers' idiosyncratic
      pronunciations. Dutch listeners learn to interpret an ambiguous sound between /s/
      and /f/ as /f/ if they hear it word-finally in Dutch words normally ending in
      /f/, but as /s/ if they hear it in normally /s/-final words. Here, we examined
      two positional effects in lexically guided retuning. In Experiment 1, ambiguous
      sounds during exposure always appeared in word-initial position (replacing the
      first sounds of /f/- or /s/-initial words). No retuning was found. In Experiment
      2, the same ambiguous sounds always appeared word-finally during exposure. Here,
      retuning was found. Lexically guided perceptual learning thus appears to emerge
      reliably only when lexical knowledge is available as the to-be-tuned segment is
      initially being processed. Under these conditions, however, lexically guided
      retuning was position independent: It generalized across syllabic positions.
      Lexical retuning can thus benefit future recognition of particular sounds
      wherever they appear in words.

PMID- 21735331
TI  - Habitual reading biases in the allocation of study time.
AB  - Item order can bias learners' study decisions and undermine the use of more
      effective allocation strategies, such as allocating study time to items in one's
      region of proximal learning. In two experiments, we evaluated whether the
      influence of item order on study decisions reflects habitual responding based on
      a reading bias. We manipulated the order in which relatively easy, moderately
      difficult, and difficult items were presented from left to right on a computer
      screen and examined selection preference as a function of item order and item
      difficulty. Experiment 1a was conducted with native Arabic readers and in Arabic,
      and Experiment 1b was conducted with native English readers and in English.
      Students from both cultures prioritized items for study in the reading order of
      their native language: Arabic readers selected items for study in a right-to-left
      fashion, whereas English readers largely selected items from left to right. In
      Experiment 2, native English readers completed the same task as participants in
      Experiment 1b, but for some participants, lines of text were rotated upside down
      to encourage them to read from right to left. Participants who read upside-down
      text were more likely to first select items on the right side of an array than
      were participants who studied right-side-up text. These results indicate that
      reading habits can bias learners' study decisions and can undermine agenda-based
      regulation.

PMID- 21735332
TI  - Inconsistent individual personality description eliminates the other-race effect.
AB  - The present study investigated the effect of individual semantic information
      displayed simultaneously with faces on the other-race effect. Arbitrary
      descriptions of the individual personalities of a set of faces were initially
      evaluated for consistency. Later, 83 naive participants were allocated to three
      groups in which they saw faces and consistent, inconsistent, or neutral
      personality information about each face. Later, they completed a recognition task
      for the faces. The other-race effect was observed only in the control group and
      the consistent-information group, but not in the inconsistent-information group.
      This showed that inconsistent individual semantic information for each face can
      help to individuate these faces and eliminated the other-race effect.

PMID- 21735334
TI  - The ABLe change framework: a conceptual and methodological tool for promoting
      systems change.
AB  - This paper presents a new approach to the design and implementation of community
      change efforts like a System of Care. Called the ABLe Change Framework, the model
      provides simultaneous attention to the content and process of the work, ensuring
      effective implementation and the pursuit of systems change. Three key strategies
      are employed in this model to ensure the integration of content and process
      efforts and effective mobilization of broad scale systems change: Systemic Action
      Learning Teams, Simple Rules, and Small Wins. In this paper we describe the ABLe
      Change Framework and present a case study in which we successfully applied this
      approach to one system of care effort in Michigan.

PMID- 21735335
TI  - Development of lidocaine-coated microneedle product for rapid, safe, and
      prolonged local analgesic action.
AB  - PURPOSE: To demonstrate rapid (~1 min) lidocaine delivery using 3M's solid
      microstructured transdermal system (sMTS) for prolonged, local analgesic action.
      METHODS: Polymeric microneedles were fabricated via injection molding and then
      dip-coated using an aqueous lidocaine formulation. The amount of lidocaine coated
      onto the microneedles was determined by high performance liquid chromatography
      (HPLC). To assess drug delivery and dermal pharmacokinetics, lidocaine-coated
      microneedles were inserted into domestic swine. Skin punch biopsies were
      collected and analyzed to determine lidocaine concentration in skin using HPLC
      mass spectrometry (LC-MS). Commercial lidocaine/prilocaine EMLA (Eutectic Mixture
      of Local Anesthetic) cream was used as comparative control. RESULTS: Lidocaine
      dissolves rapidly off the microneedles and into skin such that the 1-min wear
      time achieves or exceeds lidocaine tissue levels needed to cause analgesia. This
      therapeutic threshold (100 ng/mg) was estimated by measuring the total amount of
      lidocaine and prilocaine in skin following a 1 h EMLA application. When co
      formulated with 0.03 wt% vasoconstrictor-epinephrine, the concentration of
      lidocaine in tissue was maintained above 100 ng/mg for approximately 90 min.
      CONCLUSIONS: 3M's sMTS can be used to provide rapid delivery of lidocaine for
      local analgesia up to 90 min.

PMID- 21735336
TI  - Human cell-conditioned media produced under embryonic-like conditions result in
      improved healing time after laser resurfacing.
AB  - BACKGROUND: Laser resurfacing procedures are continuing to grow in popularity as
      patients select less invasive procedures for rejuvenation of photo-damaged and
      aging skin. However, although physicians have begun exploring options to aid in
      postlaser healing, currently available treatments have little clinical evidence
      to support their use for wounded skin. METHODS: When grown under conditions of
      very low oxygen and suspension, a simulation of the embryonic environment,
      neonatal cells have been found to produce proteins and growth factors in types
      and quantities similar to those of fetal cells. The human cell-conditioned media
      (hCCM) produced by the cells was extracted and formulated into a gel to evaluate
      its efficacy in the healing of postlaser wounds. RESULTS: A split-face clinical
      evaluation of the material was performed, with 42 subjects undergoing combination
      ablative and nonablative laser procedures. Three concentrations of the hCCM were
      tested (* 0.1, * 1.0, * 10.0), and a dose-response trend was seen in the blinded
      physician evaluation, particularly in the assessment of crusting. In addition,
      transepidermal water loss readings showed a significant difference (p <= 0.05),
      indicating a more rapid return to normal skin barrier function with the active
      treatment. Histopathologic evaluation of subject biopsies showed reduced
      inflammation and a more normal epidermal appearance in the active treatment
      sites. CONCLUSIONS: The results of this clinical evaluation support the use of
      the soluble hCCM produced under embryonic-like conditions to accelerate wound
      healing after laser resurfacing procedures. The utility of the * 10 concentration
      appears to promote more rapid, scarless wound healing after resurfacing
      procedures and more normal skin recovery.

PMID- 21735337
TI  - The impact of surgical treatment on the self-esteem of patients with breast
      hypertrophy, hypomastia, or breast asymmetry.
AB  - BACKGROUND: Currently, the concept of health includes not only the absence of
      disease but also a complete state of physical, psychological, and social well
      being with increased emphasis on the importance of self-esteem. This study aimed
      to evaluate the impact of surgical treatment on the self-esteem of patients with
      breast asymmetry, breast hypertrophy, or hypomastia. METHODS: The Rosenberg Self
      Esteem UNIFESP-EPM Scale was administered preoperatively and in the early and
      late postoperative periods to assess self-esteem. The sample comprised three
      groups of patients: the breast asymmetry group (n=35), the breast hypertrophy
      group (n=50), and the hypomastia group (n=40). RESULTS: Surgical treatment had a
      positive and similar impact on the self-esteem of the patients in the three study
      groups. CONCLUSIONS: Correction of breast asymmetry, breast hypertrophy, and
      hypomastia improved the patient's self-esteem. All three groups reported a
      similar increase in self-esteem (decrease in total scores) after breast
      reconstruction.

PMID- 21735338
TI  - A superior vertical dermal pedicle for the nipple-areola: an alternative for
      severe breast hypertrophy and ptosis.
AB  - BACKGROUND: Nipple-areola nourishment and sensation have been the main concern in
      reduction mammaplasty for severe breast hypertrophy and ptosis. Free grafting for
      the nipple-areola can cause flatness and loss of sensation. These complications
      can be improved by pedicle techniques for the nipple-areola, no matter the
      pedicle orientation. The aesthetic outcomes and complications are similar for the
      inferior and superior pedicle techniques. The pedicle length has been crucial to
      nipple-areola viability and sensation. METHODS: Using a keyhole pattern, a
      vertical flap with a superior pedicle was outlined for nipple-areola
      transposition. The mammary tissue under the flap was removed, creating a vertical
      dermal flap 7-14 cm long, and the superior pedicle was located on the new site of
      the areola marked by the pattern. Sensation was evaluated monthly by subjective
      contact testing of the four quadrants of the nipple-areola. RESULTS: The Pearson
      product-moment correlation coefficient was used to correlate the return of
      sensation with the length of the dermal flap and the amount of breast tissue
      removed. Sensation was achieved for the four quadrants 6 months after the breast
      reduction for all the patients of this series. Recovery of sensation was
      significantly greater for the superior quadrants than for the inferior quadrants
      in the first 3 months. CONCLUSIONS: The vertical dermal flap with the superior
      pedicle preserves nipple-areola nourishment and sensation. It is an alternative
      option for pedicle techniques in surgical correction of severe breast hypertrophy
      and ptosis.

PMID- 21735339
TI  - Clinical characteristics of facial keloids treated with surgical excision
      followed by intra- and postoperative intralesional steroid injections.
AB  - BACKGROUND: The physiopathogenesis of keloid scars is not well understood. This
      report aims to present the authors' experiences with facial keloids, to evaluate
      their treatment outcomes via a prospective study, and to identify risk factors
      involved in facial keloid recurrence. METHODS: Patients with facial keloids were
      treated with surgical excision followed by intra- and postoperative intralesional
      steroid injections at Kangbuk Samsung Hospital between July 2005 and June 2010.
      Of 15 keloids, 8 (53.3%) had previously been treated unsuccessfully at other
      hospitals. The follow-up period was 18 months, and therapeutic outcomes were
      evaluated based on recurrence or nonrecurrence. RESULTS: The study evaluated 17
      facial keloids in 15 patients. The overall recurrence-free rate was 76.5% after a
      follow-up period of 18 months. The authors hypothesized that the recurrence of
      keloids on the face is associated with both previous treatment and anatomic
      location. CONCLUSIONS: The authors' protocol resulted in successful outcomes for
      the treatment of facial keloids. Patients with a history of previous treatment
      and keloids in the perioral region should be monitored closely for signs of
      recurrence and managed cautiously during treatment.

PMID- 21735340
TI  - Caprine pleuropneumonia in Beetal goats [corrected].
AB  - Seroprevalence, clinical findings, and lesions of contagious caprine
      pleuropneumonia (CCPP) in Beetal goats were recorded during an outbreak. The
      overall seroprevalence of CCPP was 32.50%. Confirmation of Mycoplasma mycoides in
      serum was carried out using counter immunoelectrophoresis (CIE) technique. The
      highest CIE-positive cases were recorded in the older goats (51.72%) as compared
      to young ones. Nasal swabs collected from 39 goats showing respiratory signs were
      found positive for M. mycoides. The most consistent clinical findings were mild
      to severe cough, purulent nasal secretion, emaciation, dyspnea, increased
      respiration rate, and pyrexia. Mortality due to CCPP was 9.17%. Consolidation of
      lungs exhibited the highest frequency (100%), followed by alveolar exudation
      (90.90%) and pleural adhesion (72.72%). Among the microscopic lesions, septal
      peribronchiolar fibrosis exhibited the highest frequency (81.81%), followed by
      fibrinous pleuritis (63.63%) and peribronchiolar cuffing of mononuclear cells
      (54.54%) in lungs. From these results, it was concluded that CCPP under
      subtropical conditions has high prevalence in Beetal goats and leads to
      significant mortality.

PMID- 21735341
TI  - Effect of the administration of GnRH or hCG on time of ovulation and the onset of
      estrus-to-ovulation interval in sows in Thailand.
AB  - The aim of the present study was to evaluate the control of ovulation by the
      administration of human chorionic gonadotropin (hCG) or gonadotropin-releasing
      hormone (GnRH) at the onset of estrus. Thirty-three multiparous sows housed under
      tropical conditions and showing standing estrus within 5 days after weaning were
      included. The sows were allocated to three groups, spontaneous ovulation (control
      group, n = 10), induced ovulation using 750 IU hCG (hCG group, n = 10), and
      induced ovulation using 50 MUg GnRH (GnRH group, n = 13). The hormones were given
      at the onset of estrus and the occurrence of ovulation was monitored every 6 h by
      transrectal ultrasonography. Data for weaning-to-estrus interval, onset of estrus
      to-ovulation interval (EOI), and the length of estrus were recorded. All sows in
      the control and hCG groups ovulated, while 3 out of 13 sows treated with GnRH
      developed cystic ovaries (did not ovulate). Of those sows ovulating, the EOI of
      the hCG (40.2 +/- 1.7 h) and GnRH (37.5 +/- 3.3 h) groups were shorter than that
      of the control group (63.6 +/- 9.6 h; P < 0.05). In conclusion, the
      administration of either hCG or GnRH at the onset of estrus can control time of
      ovulation but, at the dose employed, sows receiving GnRH may develop ovarian
      cysts.

PMID- 21735342
TI  - Effects of supplementing Erythrina brucei leaf as a substitute for cotton seed
      meal on growth performance and carcass characteristics of Sidama goats fed basal
      diet of natural grass hay.
AB  - The replacement value of dried Erythrina brucei leaf for cotton seed meal (CSM)
      on growth performance and carcass characteristics was evaluated. Twenty-five
      yearling buck goats (15.8 +/- 1.4 kg) were assigned into five treatments in a
      randomized complete block design: natural grass hay alone (T1) or supplemented
      with 100% CSM (T2), 67% CSM + 33% E. brucei (T3), 33% CSM + 67% E. brucei (T4),
      and 100% E. brucei (T5) on dry matter (DM) basis. Supplemented goats consumed
      more (P < 0.05) total DM and organic matter (OM) than the non-supplemented group,
      but the intakes were not influenced (P > 0.05) by the proportion of the
      supplements. The highest (P < 0.05) crude protein (CP) intake was observed in
      goats supplemented with CSM alone, whereas the lowest intake was observed in the
      non-supplemented group. Total CP intake decreased (P < 0.05) with increasing
      levels of E. brucei in the supplement mixture. The supplemented goats gained more
      (P < 0.05) weight than the control group. Apparent DM and OM digestibility was
      higher (P < 0.05) in supplemented goats than in the non-supplemented ones, but
      similar (P > 0.05) among the supplemented group. The digestibility of CP was
      higher (P < 0.05) for supplemented goats, except in those goats fed E. brucei
      alone, than the non-supplemented group. Slaughter weight, empty body weight, hot
      carcass weight, dressing percentage, rib eye muscle area, and total edible offals
      were higher (P < 0.05) for supplemented goats than for the non-supplemented ones.
      It could be concluded that E. brucei could be used as a substitute to CSM under
      smallholder production systems.

PMID- 21735343
TI  - Victimization, smoking, and chronic physical health problems among sexual
      minority women.
AB  - BACKGROUND: Sexual minority women (SMW) have been shown to be at increased risk
      for abuse, smoking, and chronic physical health problems compared with
      heterosexual women. In the general population, abuse and smoking are associated
      with physical health problems. However, there has been little research on their
      associations among SMW. PURPOSE: The current study examined a mediational model
      of abuse, smoking, and self-reported physical health conditions in a national
      sample of SMW. METHODS: Participants (N = 1,224) were recruited via the Internet
      and completed measures of childhood trauma, adult sexual assault, smoking, body
      mass index, and chronic medical conditions. RESULTS: Structural equation modeling
      demonstrated that childhood abuse was associated with adult sexual assault,
      smoking, and physical health problems, but smoking was not a significant
      mediator. CONCLUSIONS: The results highlight the impact of childhood abuse on
      physical health problems among SMW and the need to examine other health behaviors
      that may mediate this relation.

PMID- 21735344
TI  - Sometimes, often, and always: exploring the vague meanings of frequency
      expressions.
AB  - The article describes a general two-step procedure for the numerical translation
      of vague linguistic terms (LTs). The suggested procedure consists of empirical
      and model components, including (1) participants' estimates of numerical values
      corresponding to verbal terms and (2) modeling of the empirical data using fuzzy
      membership functions (MFs), respectively. The procedure is outlined in two
      studies for data from N = 89 and N = 109 participants, who were asked to estimate
      numbers corresponding to 11 verbal frequency expressions (e.g., sometimes).
      Positions and shapes of the resulting MFs varied considerably in symmetry,
      vagueness, and overlap and are indicative of the different meanings of the vague
      frequency expressions. Words were not distributed equidistantly across the
      numerical scale. This has important implications for the many questionnaires that
      use verbal rating scales, which consist of frequency expressions and operate on
      the premise of equidistance. These results are discussed for an exemplar
      questionnaire (COPSOQ). Furthermore, the variation of the number of prompted LTs
      (5 vs. 11) showed no influence on the words' interpretations.

PMID- 21735345
TI  - Photostability and interaction of ascorbic acid in cream formulations.
AB  - The kinetics of photolysis of ascorbic acid in cream formulations on UV
      irradiation has been studied using a specific spectrophotometric method with a
      reproducibility of +/- 5%. The apparent first-order rate constants (k(obs)) for
      the photolysis of ascorbic acid in creams have been determined. The photoproducts
      formed in the cream formulations include dehydroascorbic acid and 2,3
      diketogulonic acid. The photolysis of ascorbic acid appears to be affected by the
      concentration of active ingredient, pH, and viscosity of the medium and
      formulation characteristics. The study indicates that the ionized state and redox
      potentials of ascorbic acid are important factors in the photostability of the
      vitamin in cream formulations. The viscosity of the humectant present in the
      creams appears to influence the photostability of ascorbic acid. The results show
      that the physical stability of the creams is an important factor in the
      stabilization of the vitamin. In the cream formulations stored in the dark,
      ascorbic acid undergoes aerobic oxidation and the degradation is affected by
      similar factors as indicated in the photolysis reactions. The rate of oxidative
      degradation in the dark is about seventy times slower than that observed in the
      presence of light.

PMID- 21735346
TI  - Safe opioid prescribing: a long way to go.

PMID- 21735347
TI  - To comfort, always.

PMID- 21735348
TI  - Effectiveness of intensive physician training in upfront agenda setting.
AB  - BACKGROUND: Patients want all their concerns heard, but physicians fear losing
      control of time and interrupt patients before all concerns are raised. OBJECTIVE:
      We hypothesized that when physicians were trained to use collaborative upfront
      agenda setting, visits would be no longer, more concerns would be identified,
      fewer concerns would surface late in the visit, and patients would report greater
      satisfaction and improved functional status. DESIGN AND PARTICIPANTS: Post-only
      randomized controlled trial using qualitative and quantitative methods. Six
      months after training (March 2004-March 2005) physician-patient encounters in two
      large primary care organizations were audio taped and patients (1460) and
      physicians (48) were surveyed. INTERVENTION: Experimental physicians received
      training in upfront agenda setting through the Establishing Focus Protocol,
      including two hours of training and two hours of coaching per week for four
      consecutive weeks. MAIN MEASURES: Outcomes included agenda setting behaviors
      demonstrated during the early, middle, and late encounter phases, visit length,
      number of raised concerns, patient and physician satisfaction, trust and
      functional status. KEY RESULTS: Experimental physicians were more likely to make
      additional elicitations (p < 0.01) and their patients were more likely to
      indicate agenda completion in the early phase of the encounter (p < 0.01).
      Experimental group patients and physicians raised fewer concerns in the late
      encounter phase (p < 0.01). There were no significant differences in visit
      length, total concerns addressed, patient or provider satisfaction, or patient
      trust and functional status CONCLUSION: Collaborative upfront agenda setting did
      not increase visit length or the number of problems addressed per visit but may
      reduce the likelihood of "oh by the way" concerns surfacing late in the
      encounter. However, upfront agenda setting is not sufficient to enhance patient
      satisfaction, trust or functional status. Training focused on physicians instead
      of teams and without regular reinforcement may have limited impact in changing
      visit content and time use.

PMID- 21735349
TI  - The endodermis--development and differentiation of the plant's inner skin.
AB  - Controlling external compound entrance is essential for plant survival. To set up
      an efficient and selective sorting of nutrients, free diffusion via the apoplast
      in vascular plants is blocked at the level of the endodermis. Although we have
      learned a lot about endodermal specification in the last years, information
      regarding its differentiation is still very limited. A differentiated endodermal
      cell can be defined by the presence of the "Casparian strip" (CS), a cell wall
      modification described first by Robert Caspary in 1865. While the anatomical
      description of CS in many vascular plants has been very detailed, we still lack
      molecular information about the establishment of the Casparian strips and their
      actual function in roots. The recent isolation of a novel protein family, the
      CASPs, that localizes precisely to a domain of the plasma membrane underneath the
      CS represents an excellent point of entry to explore CS function and formation.
      In addition, it has been shown that the endodermis contains transporters that are
      localized to either the central (stele-facing) or peripheral (soil-facing) plasma
      membranes. These features suggest that the endodermis functions as a polar plant
      epithelium.

PMID- 21735350
TI  - Induction of mitogynogenetic diploids and identification of WW super-female using
      sex-specific SSR markers in half-smooth tongue sole (Cynoglossus semilaevis).
AB  - The half-smooth tongue sole (Cynoglossus semilaevis) is an important cultured
      marine fish as well as a promising model fish for the study of sex determination
      mechanisms. In the present study, a protocol for artificial induction of
      mitogynogenesis by hydrostatic pressure using heterologous sperm was developed in
      half-smooth tongue sole in order to assess homozygosity of gynogens and to
      identify WW super-female. The optimal initiation time for pressure shock of
      mitogynogenetic embryos was determined to be 21.5 min after insemination when
      water temperature is at 22-23 degrees C, while the optimal pressure and treatment
      duration were determined to be 70 MPa for 4 min. About 1,500 mitogynogenetic
      diploid larvae were obtained. Ten tongue sole microsatellite markers were used
      for homozygosity analysis of 24 mitogynogenetic larvae. Among the 24 larvae, the
      percentage of homozygosity ranged from 73.91% to 87.50% with an average
      homozygosity of 80.54%. Sex-specific simple sequence repeat (SSR) markers, CseF
      SSR1, were isolated and used for identifying WW super-female mitogynogens in the
      tongue sole. The amplification of genomic DNA using the sex-specific SSR marker
      produced one DNA band of 206 bp in ZZ males, two DNA bands of 206 and 218 bp in
      ZW females, and one DNA band of 218 bp in WW super-females. Four WW "super
      female" gynogens were observed in 39 mitogynogenetic diploids, indicating a ZW
      sex determination mechanism in the tongue sole. Thus, a protocol for the
      induction of artificial mitogynogenesis has been developed for the first time in
      half-smooth tongue sole, and the WW super-female diploids were identified in the
      mitogynogens by sex-specific SSR markers. These findings lay the foundation and
      provide important tool for the elaboration of sex determination mechanism,
      generation of WW super-females, and development of clone line and breeding of all
      female stock in the half-smooth tongue sole.

PMID- 21735351
TI  - Dilated SMV in colon cancer--is there any significance.
AB  - OBJECTIVE: Changes in splanchnic circulation have been seen in patients with
      colorectal cancer. We have previously reported that the inferior mesenteric vein
      is dilated in rectal cancer. We wanted to assess whether the superior mesenteric
      vein (SMV) is dilated in right-sided colon cancer. MATERIALS AND METHODS: From a
      colorectal database, three cohorts were formed: right colon cancer, rectal
      cancer, and normal. The SMV (2 cm proximal to the confluence of the SMV and
      portal vein) and the gastrocolic trunk (GCT) were saved and anonymized. The short
      axis diameter of the vein was measured independently by three radiologists.
      RESULTS: The diameter of the SMV and GCT was higher in the right colon group than
      the other two groups. There was no correlation with the stage of tumor
      (locoregional or metastatic). CONCLUSION: Patients with right colon cancer showed
      a significantly increased mean SMV diameter at presentation, which may be due to
      increased venous return secondary to neovascularization. Further studies are
      required to evaluate this further.

PMID- 21735352
TI  - Cochlear hearing loss in patients with Laron syndrome.
AB  - The aim of this prospective clinical study was to test auditory function in
      patients with Laron syndrome, either untreated or treated with insulin-like
      growth factor I (IGF-I). The study group consisted of 11 patients with Laron
      syndrome: 5 untreated adults, 5 children and young adults treated with
      replacement IGF-I starting at bone age <2 years, and 1 adolescent who started
      replacement therapy at bone age 4.6 years. The auditory evaluation included pure
      tone and speech audiometry, tympanometry and acoustic reflexes, otoacoustic
      emissions, loudness dynamics, auditory brain stem responses and a hyperacusis
      questionnaire. All untreated patients and the patient who started treatment late
      had various degrees of sensorineural hearing loss and auditory hypersensitivity;
      acoustic middle ear reflexes were absent in most of them. All treated children
      had normal hearing and no auditory hypersensitivity; most had recordable middle
      ear acoustic reflexes. In conclusion, auditory defects seem to be associated with
      Laron syndrome and may be prevented by starting treatment with IGF-I at an early
      developmental age.

PMID- 21735353
TI  - Validation of cofilin-1 as a biomarker in non-small cell lung cancer: application
      of quantitative method in a retrospective cohort.
AB  - PURPOSE: Cofilin is a cytoskeletal protein whose overexpression has been
      associated with aggressiveness in several types of malignancies. Here, we
      established and optimized a simple semi-quantitative immunohistochemistry (SQ
      IHC) method for cofilin quantification in tumor biopsies, and applied it in a
      retrospective cohort of NSCLC patients aiming at validating the use of cofilin-1
      as a prognostic biomarker. METHODS: The SQ-IHC method for cofilin-1
      quantification was established and applied in a NSCLC cohort. An archival
      collection of biopsies from 50 patients with clinicopathological information and
      5 years follow-up was accessed. Association between cofilin-1 immunocontent and
      clinical outcome was assessed using standard Kaplan-Meier mortality curves and
      the log-rank test. To evaluate the robustness of our findings, three different
      partitional clustering strategies were used to stratify patients into two groups
      according to the biomarker expression level (hierarchical clustering, Kmeans and
      median cutoff). RESULTS: In all the three different partitional clustering we
      used, survival analysis showed that patient with high cofilin-1 immunocontent had
      a lower overall survival rate (P < 0.05), and could be used to discriminate
      between good and bad prognosis. No other correlation was found when the variables
      age, sex or histological type were tested in association with patients outcome or
      with cofilin immunocontent. CONCLUSIONS: Our method showed good
      sensitivity/specificity to indicate the outcome of patients according to their
      cofilin immunocontent in biological samples. Its application in a retrospective
      cohort and the results presented here are an important step toward the validation
      process of cofilin-1 as a prognostic biomarker.

PMID- 21735354
TI  - Phase IB study of sorafenib in combination with gemcitabine and cisplatin in
      patients with refractory solid tumors.
AB  - PURPOSE: Sorafenib (BAY 43-9006), a multikinase inhibitor, has been shown to
      inhibit tumor growth and tumor angiogenesis by targeting Raf kinase, vascular
      endothelial growth factor receptor, and platelet-derived growth factor receptor.
      This study investigated the safety, pharmacokinetics, and preliminary efficacy of
      sorafenib in combination with gemcitabine and cisplatin. METHODS: Patients with
      advanced solid tumors were treated with 75 mg/m(2) cisplatin on day 1 and 1,250
      mg/m(2) gemcitabine on days 1 and 8 of each 21-day cycle. On day 5 of cycle 1,
      sorafenib 400 mg twice daily was started and continued throughout the complete
      treatment cycles without interruption. RESULTS: Nineteen patients were valid for
      safety analysis. The most frequent toxicities related to the cytotoxic agents
      were hematological disorders. Sorafenib-related toxicities were skin-related,
      gastrointestinal, and constitutional symptoms. No clinically relevant
      pharmacokinetic drug-drug interaction between sorafenib, cisplatin, and
      gemcitabine was detected. AUC(0-72) and  C (max) of total and unbound platinum
      were only marginally changed by concomitant sorafenib. Concomitant sorafenib
      increased mean AUC and  C (max) of gemcitabine by 12 and 21%. CONCLUSIONS:
      Sorafenib as continuous oral treatment in combination with gemcitabine and
      cisplatin demonstrated an acceptable safety profile. No clinically relevant
      pharmacokinetic interaction was detected. Preliminary antitumor activity,
      pharmacokinetic, and safety data support the recommendation of 400 mg sorafenib
      twice daily in combination with cisplatin and gemcitabine to be further evaluated
      in clinical studies.

PMID- 21735355
TI  - Incidence of serious respiratory infections in patients with rheumatoid arthritis
      treated with tocilizumab.
AB  - We aimed to demonstrate the incidence of serious respiratory infections in
      patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ)
      monotherapy. We analyzed the incidence of serious respiratory infections in 601
      RA patients enrolled in TCZ clinical trials and their extension studies (TCZ
      cohort) and in 601 age- and sex-standardized RA patients treated in daily
      clinical practice at Tokyo Women's Medical University (IORRA subsample cohort).
      The rates of serious respiratory infections were 1.77 per 100 patient-years from
      1999 to 2008 in the TCZ cohort and 0.53 per 100 patient-years from 2000 to 2009
      in the IORRA subsample cohort. With the IORRA subsample cohort regarded as a
      standard population, the standardized incidence ratio (SIR) of serious
      respiratory infection in the TCZ cohort was 3.64 [95% confidence interval (CI)
      2.56-5.01], standardized for age and sex; 2.35 (95% CI 1.66-3.24), standardized
      for age sex, and corticosteroid use; 1.85 (95% CI 1.30-2.55), standardized for
      age sex, and pre-existing pulmonary involvement; and 2.41 (95% CI 1.68-3.34)
      standardized for age sex, and disease activity. The risk of serious respiratory
      infection in the TCZ cohort was approximately double that in the IORRA subsample
      cohort after standardizing for corticosteroid use, pre-existing pulmonary
      involvement, or disease activity. This is comparable to the risk reported when
      tumor necrosis factor (TNF) inhibitors are used.

PMID- 21735356
TI  - Predicting the effects of chemoradiotherapy for squamous cell carcinoma of the
      esophagus by induction chemotherapy response assessed by positron emission
      tomography: toward PET-response-guided selection of chemoradiotherapy or
      esophagectomy.
AB  - BACKGROUND: We have developed a treatment protocol for esophageal cancer
      involving a single course of induction chemotherapy followed by
      chemoradiotherapy. This study aimed to determine if it was possible to predict
      the effects of chemoradiotherapy on the basis of the response to induction
      chemotherapy, assessed by positron emission tomography (PET). METHODS: Sixteen
      patients with Stage II-IVA esophageal cancer were treated using this protocol
      from April 2007 to July 2010. Chemotherapy involved a fluorouracil and platinum
      based combination regimen. All patients received PET scans before and 12-24 days
      after the beginning of induction chemotherapy. Associations between the response
      to induction chemotherapy assessed by PET and the effects of chemoradiotherapy
      were evaluated. RESULTS: Induction chemotherapy followed by chemoradiotherapy
      resulted in complete response (CR) in 10 of the 16 patients. The reduction in
      maximum standardized uptake value (SUV(max)) was 58 +/- 12% in patients with CR
      (n = 10), compared with 14 +/- 16% in patients without CR (n = 6) (P < 0.0001).
      Using a cut-off value of 55% for SUV(max) reduction rate, eight of 10 cancers
      with CR and six of six cancers without CR were correctly identified, providing a
      sensitivity and specificity of 80 and 100%, respectively. The overall 1-year
      survival rates for patients with an SUV(max) reduction rate >55% (responders)
      were 100%, compared with 60% for patients with an SUV(max) reduction rate <=55%
      (non-responders), respectively. CONCLUSIONS: The response to a single course of
      induction therapy assessed by PET was significantly associated with the effects
      of chemoradiotherapy.

PMID- 21735357
TI  - [Metastatic neuroendocrine neoplasms. Non-surgical treatment strategies].
AB  - The clinical presentation of neuroendocrine neoplasms (NEN) varies depending on
      the site of origin, functional activity, histological differentiation and tumor
      growth behavior. Therapeutic strategies aim to improve the symptoms of clinical
      syndromes related to the secretion of amines and peptides, inhibit tumor growth
      and prevent complications. Novel molecular targeted drug therapies offer new
      treatment options in addition to established therapies, such as somatostatin
      analogs and chemotherapy. The precise positioning of these drugs and of peptide
      receptor radionuclide therapy still needs to be defined. In general, the
      different medical treatments are used in a sequential way and are in part
      combined with surgical and loco-regional/ablative procedures in a highly
      individualized approach. In certain clinical conditions, however, established
      treatment strategies are followed. This review presents the management of
      patients with small intestinal and pancreatic NEN with respect to the
      functionality and tumor grading. The use of novel targeted drug therapy is
      included in a therapeutic algorithm.

PMID- 21735358
TI  - [Principles of perioperative coagulation management].
AB  - The coagulation system is a complex network of interacting proteins and cells
      with extensive sensitivity, amplification and control pathways. The system
      represents a delicate balance between procoagulant and anticoagulant as well as
      profibrinolytic and antifibrinolytic activities. Clinically relevant phenotypes,
      e.g. bleeding and thrombosis, occur immediately when this balance is no longer in
      equilibrium. A correct understanding of the complex coagulation pathophysiology
      in the perioperative setting is essential for an effective treatment. In a
      bleeding patient, patient's history, clinical findings, routine and advanced
      laboratory coagulation testing as well as point-of-care coagulation monitoring
      help to reliably and readily identify the underlying coagulation disorder. Modern
      coagulation management is proactive, individualized, balanced and follows clearly
      defined algorithms. Coagulopathic bleeding can be successfully controlled with
      specific interventions in the coagulation system.

PMID- 21735359
TI  - Direct correlation function in equilibrium polymers by PRISM equations.
AB  - In this work, we calculate the direct correlation function and the structure
      factor of equilibrium polymers in the framework of the PRISM theory. We study
      especially the effect of the polydispersity and the monomer density on these
      functions. The intermolecular pair distribution function is compared with
      simulation results using a recent equilibrium polymer chains model. A scaling
      analysis is carried out for the direct correlation function.

PMID- 21735361
TI  - New approaches to addiction treatment based on learning and memory.
AB  - Preclinical studies suggest that physiological learning processes are similar to
      changes observed in addicts at the molecular, neuronal, and structural levels.
      Based on the importance of classical and instrumental conditioning in the
      development and maintenance of addictive disorders, many have suggested cue
      exposure-based extinction training of conditioned, drug-related responses as a
      potential new treatment of addiction. It may also be possible to facilitate this
      extinction training with pharmacological compounds that strengthen memory
      consolidation during cue exposure. Another potential therapeutic intervention
      would be based on the so-called reconsolidation theory. According to this
      hypothesis, already-consolidated memories return to a labile state when
      reactivated, allowing them to undergo another phase of consolidation
      reconsolidation, which can be pharmacologically manipulated. These approaches
      suggest that the extinction of drug-related memories may represent a viable
      treatment strategy in the future treatment of addiction.

PMID- 21735360
TI  - B lymphocyte lineage specification, commitment and epigenetic control of
      transcription by early B cell factor 1.
AB  - Early B cell factor 1 (EBF1) is a transcription factor that is critical for both
      B lymphopoiesis and B cell function. EBF1 is a requisite component of the B
      lymphocyte transcriptional network and is essential for B lineage specification.
      Recent studies revealed roles for EBF1 in B cell commitment. EBF1 binds its
      target genes via a DNA-binding domain including a unique 'zinc knuckle', which
      mediates a novel mode of DNA recognition. Chromatin immunoprecipitation of EBF1
      in pro-B cells defined hundreds of new, as well as previously identified, target
      genes. Notably, expression of the pre-B cell receptor (pre-BCR), BCR and
      PI3K/Akt/mTOR signaling pathways is controlled by EBF1. In this review, we
      highlight these current developments and explore how EBF1 functions as a tissue
      specific regulator of chromatin structure at B cell-specific genes.

PMID- 21735362
TI  - Carbohydrate counting of food.
AB  - QUESTIONS UNDER STUDY: Carbohydrate counting is a principal strategy in
      nutritional management of type 1 diabetes. The Nutri-Learn buffet (NLB) is a new
      computer-based tool for patient instruction in carbohydrate counting. It is based
      on food dummies made of plastic equipped with a microchip containing relevant
      food content data. The tool enables the dietician to assess the patient's food
      counting abilities and the patient to learn in a hands-on interactive manner to
      estimate food contents such as carbohydrate content. METHODS: Multicentre
      randomised controlled trial in 134 patients with type 1 diabetes comparing the
      use of the Nutri-Learn buffet in determining and improving ability to estimate
      the carbohydrate content of food with the use of conventional counselling tools
      (i.e. pictures and tables). RESULTS: The NLB group showed significantly better
      carbohydrate estimation values than the control group. In particular, there was a
      significant improvement in estimation of starches, fruits and sweets. The NLB was
      preferred by patients and dieticians in that rating of carbohydrate was closer to
      reality than the use of conventional tools, and since the tool has a play
      element, is interactive and adjustable, and can be used with only minimal
      knowledge of a specific language. CONCLUSIONS: Adjustment of preprandial insulin
      doses to the amounts of dietary carbohydrates ingested during the subsequent meal
      resulted in improved metabolic control in previous studies. The present study
      demonstrated that the new tool (Nutri-Learn buffet) improved teaching and
      learning of carbohydrate counting. In addition, it allowed an objective
      assessment of the carbohydrate counting skills of patients by the dietician. The
      findings therefore suggest that the tool is helpful in nutritional counselling of
      patients with diabetes mellitus.

PMID- 21735363
TI  - Whole-body vibration training elevates creatine kinase levels in sedentary
      subjects.
AB  - PRINCIPLES: Whole body vibration (WBV) is an increasingly popular modality of
      muscle training, especially in sedentary subjects. We hypothesised that the
      vigorous muscle contractions elicited by WBV can cause muscle damage expressed as
      an elevation in muscle enzymes. METHODS: Twenty inactive subjects, ten male and
      ten female, aged 22.7 +/- 2.6, BMI 22.4 +/- 2.1 were included based on the
      absence of regular physical activity as defined by international guidelines, and
      no history of recent trauma, musculoskeletal pathology, implanted prosthetics,
      cardiovascular disease or drug intake. The intervention consisted of one bout of
      high intensity WBV corresponding to a typical training session, involving all the
      major muscle groups. Plasma levels of muscle enzymes prior to and at 24, 48 and
      96 hours post exercise (creatine kinase - CK, MB fraction, troponin I,
      aminotransferases and lactate dehydrogenase) were measured. In addition, blood
      lactate was assayed immediately after exercise. Delayed onset muscle soreness
      (DOMS) was evaluated using a visual analogical scale. RESULTS: Five participants
      (25%) showed a significant increase in post exercise CK levels (> double of
      baseline). Maximal value was 3520 U/l. No change was observed in CK-MB or
      troponin I. Lactate increased to 10.0 +/- 2.4 in men and 6.9 +/- 2.4 in women.
      All participants had some degrees of DOMS, without correlation to enzymatic
      changes. DISCUSSION: WBV can provoke high CK elevation in healthy, medication
      free inactive subjects. Such an elevation is transient and harmless, but could be
      wrongly attributed to drug induced myopathy, as in patients treated with statins.
      Practitioners should bear this in mind before discontinuing a potential life
      saving drug.

PMID- 21735364
TI  - Regional differences of glycaemic control in patients with type 2 diabetes
      mellitus in Switzerland: a national cross-sectional survey.
AB  - AIMS: We investigated contemporary diabetes care, quality of glycaemic control,
      and progression of obesity in patients with diabetes mellitus in different
      cultural regions within Switzerland. METHODS: Overall, 1121 patients treated for
      type 2 diabetes mellitus by 134 general practitioners were enrolled in this
      representative, national, cross-sectional survey and were followed
      retrospectively from the start of diabetes treatment. Patients were classified
      into four cultural regions; the German, French, Italian and Romansh speaking
      parts of Switzerland. RESULTS: During 5.5 +/- 5.1 years of diabetes treatment
      (retrospective survey), mean HbA1c decreased from 8.28 +/- 2.01% to 7.03 +/-
      1.24%, fasting glucose decreased from 9.97 +/- 3.86 to 7.52 +/- 2.23 mmol/l, and
      BMI decreased from 30.2 +/- 5.5 to 29.8 +/- 5.6 kg/m2 (p <0.001 for all
      parameters). Insulin therapy was associated with a larger improvement of mean
      HbA1c (-1.66 +/- 2.33% vs. -1.15 +/- 1.91%, p = 0.001) and an increase in BMI
      (+0.36 +/- 2.92 vs. -0.63 +/- 2.60 kg/m2, p <0.001). At the time when the cross
      sectional survey was conducted, the mean HbA1c and fasting glucose were higher in
      the Italian part compared to other regions (7.72 +/- 1.60% and 9.03 +/- 2.49
      mmol/l, respectively, p <0.001), and lower in the German part (6.89 +/- 1.02% and
      7.25 +/- 2.02 mmol/l, respectively, p <0.001). In comparison to other regions,
      biguanides were more often used in the French part (86.1% versus 75.7%), insulin
      secretagogues in the Italian part (69.9% versus 37.8%), thiazolidinediones in the
      Romansh part (34.1% versus 17.8%), and insulin was more often used in the German
      part of Switzerland (27.0% versus 17.1%) (p <0.01 for all parameters).
      CONCLUSIONS: Efforts to identify regional-cultural differences and attempts to
      overcome associated potential barriers should be emphasised in any health care
      system when aiming for better diabetic patient care.

PMID- 21735365
TI  - Low-dose recombinant factor VIIa for massive bleeding: a single centre
      observational cohort study with 73 patients.
AB  - QUESTIONS UNDER STUDY: recombinant activated factor VII (rFVIIa) is used off
      label for massive bleeding. There is no convincing evidence of the benefits of
      this practice and the minimal effective dose is unknown. The aim of the study was
      to evaluate our in-house guideline recommending a low dose of 60 MUg/kg for off
      label use of rFVIIa. METHODS: observational cohort study at the Inselspital Bern,
      a tertiary care University Hospital in Switzerland. All patients with massive
      bleeding treated off-label with rFVIIa between January 2005 and December 2007
      were included. Survival, change of bleeding and transfusion rates, coagulation
      parameters and complications were analysed. RESULTS: seventy-three patients
      received rFVIIa. Severe haemorrhage was documented by a bleeding rate of 1000
      mL/h (median; interquartile range 350-3000) and total volume replacement of 11.9
      L (6.6-15.2) before administration of rFVIIa. The median rFVIIa-dose was 64
      MUg/kg (56-71). rFVIIa was administered once in 79% patients, twice in 18%. The
      bleeding rate was reduced in 82% of the patients. Transfused packed red blood
      cells decreased from 14 units (8-22) over 4.9 h (2.5-8.8) before rFVIIa to 2 (0
      6) in 24 h thereafter, platelet concentrates from 2 units (1-3) to 1 (0-2) and
      FFP from 11 units (6-16) to 2 (0-9). In-hospital mortality was 14% within 24 h
      and 32% at day 30. There were two arterial thromboembolic complications possibly
      related to rFVIIa. CONCLUSION: a single injection of 60 MUg/kg rFVIIa, a lower
      dose than usually recommended, appears to be efficacious in controlling massive
      bleeding with a very low complication rate.

PMID- 21735366
TI  - MRSA admission screening in a low prevalence setting - much ado about nothing?
AB  - OBJECTIVE: To prospectively evaluate new guidelines for MRSA admission screening
      and pre-emptive isolation implemented in response to a doubling of newly
      diagnosed MRSA patients in 2007. DESIGN: One-year surveillance (04/2008-03/2009).
      SETTING: Patients admitted to the tertiary-care hospital in St. Gallen (700 beds)
      and 10 affiliated public hospitals (890 beds) in Eastern Switzerland (MRSA rate
      2.5% in isolates). PATIENTS: Except for known MRSA carriers, all patients who
      underwent admission screening in accordance with the guidelines and all MRSA
      patients newly detected by a clinical sample were included. METHODS: Depending on
      epidemiological factors (stay in a foreign hospital, a Swiss hospital with known
      high MRSA prevalence, or a chronic care facility) and personal risk factors
      (wound, tracheostoma, urinary catheter, IVDU), patients were risk stratified into
      screening and isolation, only screening or no screening at all. MRSA admission
      screening included nasal, throat and axillary/inguinal swabs, supplemented by
      wound swabs, urine and respiratory secretion whenever appropriate (conventional
      culture). RESULTS: A total of 6/161 (3.7%) MRSA admission screenings yielded
      positive results (number needed to screen: 27). 2/32 (6.3%) pre-emptively
      isolated patients were positive (number needed to isolate: 16). Only 6/27 (22.2%)
      newly diagnosed MRSA patients were detected by admission screening, and the
      remaining patients were detected by clinical sample during hospitalisation. A
      total of 80% of the MRSA positive patients had wounds. Swabs of axilla/inguina
      did not increase the sensitivity of the admission screening. CONCLUSIONS: In the
      setting of low MRSA prevalence, admission screening of patients at high risk for
      MRSA carriage detected only one out of five newly diagnosed MRSA patients,
      emphasising the importance of standard precautions for the prevention of MRSA
      transmission.

PMID- 21735368
TI  - [Clinical and diagnostic findings in chronic immune-mediated neuropathies].

PMID- 21735369
TI  - Urethral extrusion of a peritoneal catheter in a patient with a neobladder: a
      rare complication of shunt insertion.
AB  - The insertion of a ventriculoperitoneal shunt (VPS) is considered the standard of
      care for several forms of hydrocephalus. Abdominal complications are most common
      with this procedure, comprising up to 30% of all shunt-related problems.
      Conversely, visceral perforation or extrusion of the shunt apparatus is rare.
      Herein we report a rare complication of VPS insertion in which the peritoneal
      catheter was spontaneously extruded through the urethra of a patient with a
      neobladder. We further discuss the pathogenesis, diagnosis, and treatment of this
      condition.

PMID- 21735370
TI  - Reduced porcine islet isolation yield in the presence of hyperemic islets.
AB  - When studying histological characteristics of porcine pancreata in relation to
      islet isolation, a remarkably high number of hyperemic islets (HIs) was
      encountered. The abnormalities observed in these HIs ranged from a single dilated
      vessel to hemorrhages extending into the surrounding exocrine tissue. The aim of
      the present study was to compare pancreata with and without HI on islet isolation
      outcomes. This study involved a histological examination of 143 purebred (74
      juvenile and 69 adult) and 47 crossbred (only juvenile) porcine pancreata. Islet
      isolation was performed in 48 purebred adult pigs and in 25 crossbred pigs.
      Tissue samples were stained with Aldehyde Fuchsine. The presence of HIs was
      scored semi-quantitatively (HI-, HI+). We observed HIs in 48% of the purebred and
      in 68% of the crossbred pigs. However, only 3.3+/-3.1% and 3.1+/-4.7% of all
      assessed islets was hyperemic in HI+ pancreata in purebred and crossbred pigs,
      respectively. In both groups, significantly higher endocrine cell mass was found
      in the HI+ pancreata (p<0.01). When the higher endocrine cell mass was taken into
      account, we found significantly lower yields in the HI+ pancreata in both
      purebred and crossbred pigs (p=0.03 in both groups). The presence of HIs occurs
      frequently in porcine donor-pancreata and is associated with reduced isolation
      outcomes.

PMID- 21735371
TI  - Criteria for decision making after endoscopic resection of well-differentiated
      rectal carcinoids with regard to potential lymphatic spread.
AB  - BACKGROUND AND STUDY AIM: Rectal carcinoids are low-grade malignancies that are
      usually treated by endoscopic resection. However, on pathologic examination,
      resection margins that are positive for carcinoid cells are frequently found.
      Patient outcomes were reviewed after endoscopic resection of rectal carcinoids
      and the clinical significance of possible residual disease, as defined by
      pathologic and endoscopic examination, was evaluated. PATIENTS AND METHODS: The
      medical records and endoscopic findings of 347 patients presenting with rectal
      carcinoids to 14 university hospitals in Korea between January 1999 and June 2007
      were retrospectively analyzed. RESULTS: A total of 304 patients were treated with
      endoscopic resection, and 43 patents were treated with surgery. In the endoscopic
      resection group, the complete resection rate was 88.2% based on endoscopic
      appearance (CR-E) and 60.2% based on pathologic evaluation (CR-P). The agreement
      between CR-E and CR-P was low (kappa=0.192). No residual tumors were found in 77
      of 85 patients (90.6%) who were CR-E but not CR-P and who had endoscopic biopsy
      taken at 24-month follow-up. The receiver-operating characteristic curve
      identified an optimal cut-off value of 10.5 mm, at which the sensitivity and the
      specificity for metastasis were 100% and 89%, respectively. The risk factors for
      metastasis by multivariate analysis were tumor size, increased mitotic rate, and
      lymphovascular invasion. CONCLUSIONS: Endoscopic resection is a safe and
      effective modality for treating well-differentiated rectal carcinoids smaller
      than 10 mm in diameter. Discrepancies were observed between CR-E and CR-P. The
      risk factors for metastasis were tumor size, increased mitotic rate, and
      lymphovascular invasion.

PMID- 21735372
TI  - Stereotactic biopsy of a cerebral capillary telangiectasia after a misleading F
      18-FET-PET.

PMID- 21735373
TI  - Two different primary brain tumors, glioblastoma multiforme and pituitary
      adenoma, in association with colorectal carcinoma: an unusual case of nonfamilial
      Turcot's syndrome?

PMID- 21735374
TI  - Reporting of diagnostic cytogenetic results.
AB  - This appendix, developed by the staff at the Clinical Cytogenetics Laboratory at
      the Brigham and Women's Hospital, includes a comprehensive list of current
      "macros" or standardized statements used to facilitate reporting of cytogenetic
      results. These are provided as a reference for other laboratories. The statements
      are organized under the general categories of constitutional or acquired
      abnormalities and subdivided into analysis type (GTG-banding or FISH). Multi
      specimen usage macros are included that can be applied to two or more specimen
      types.

PMID- 21735375
TI  - Testing hygrometers used in cytogenetics laboratories for metaphase preparation.
AB  - This protocol describes procedures for checking small laboratory hygrometers for
      accuracy at three relative humidity (rh) levels. The work arose out of the need
      to provide laboratory assessors with documentary evidence that the hygrometer
      used to monitor humidity in the vicinity of the laboratory where medical
      cytogenetics testing slides are prepared and dried in the ambient environment is
      reproducible and sufficiently accurate. The procedure is based upon the
      physicochemical principle that when water or certain saturated salt solutions are
      placed into a sealed environment, the humidity will equilibrate to well defined
      levels. We choose to check our hygrometers at three points: 95%, 75%, and 33% rh,
      using distilled water, saturated sodium chloride solution, and saturated
      magnesium chloride solution, respectively. Our results have demonstrated that the
      procedure is convenient and of sufficient accuracy to be fit for this annual
      hygrometer validation purpose. The procedure takes 24 hr per relative humidity
      point checked.

PMID- 21735376
TI  - Analysis of gene-gene interactions.
AB  - The goal of this unit is to introduce gene-gene interactions (epistasis) as a
      significant complicating factor in the search for disease susceptibility genes.
      This unit begins with an overview of gene-gene interactions and why they are
      likely to be common. Then, it reviews several statistical and computational
      methods for detecting and characterizing genes with effects that are dependent on
      other genes. The focus of this unit is genetic association studies of discrete
      and quantitative traits because most of the methods for detecting gene-gene
      interactions have been developed specifically for these study designs.

PMID- 21735377
TI  - An overview of biochemical genetics.
AB  - Biochemical genetics focuses on the pathophysiology, diagnosis, and treatment of
      inherited metabolic disorders. While individually rare, the combined incidence of
      these diseases is likely greater than 1:3000 live births. These conditions may
      present in the neonatal period as an acute, life-threatening illness, or may
      manifest later in childhood with symptoms of progressive neurodegeneration,
      skeletal abnormalities, and/or dysmorphia. The purpose of this introductory unit
      is to provide an overview of the different clinical categories of metabolic
      disorders, modern diagnostic methods, and treatment options.

PMID- 21735378
TI  - Diagnosis of copper transport disorders.
AB  - Techniques for the diagnosis of copper transport disorders are increasingly
      important due to recent recognition of previously unappreciated clinical
      phenotypes and emerging advances in the treatment of these conditions. Here, we
      collate the diagnostic approaches and techniques currently employed for
      biochemical and molecular assessment of at-risk individuals in whom abnormal
      copper metabolism is suspected.

PMID- 21735379
TI  - WITHDRAWN: Bronchopulmonary hygiene physical therapy for chronic obstructive
      pulmonary disease and bronchiectasis.
AB  - BACKGROUND: Bronchopulmonary hygiene physical therapy is a form of chest physical
      therapy including chest percussion and postural drainage to remove lung
      secretions. These are applied commonly to patients with both acute and chronic
      airway diseases. Despite controversies in the literature regarding its efficacy,
      it remains in use in a variety of clinical settings. The various forms of this
      therapy are labour intensive and need to be evaluated. OBJECTIVES: The objective
      of this review was to assess the effects of bronchial hygiene physical therapy in
      people with chronic obstructive pulmonary disease and bronchiectasis. SEARCH
      STRATEGY: We searched the Cochrane Airways Group trials register and reference
      lists of articles up to January 2007. We also wrote to study authors. SELECTION
      CRITERIA: Randomised trials in which postural drainage, chest percussion,
      vibration, chest shaking, directed coughing or forced exhalation technique was
      compared to other drainage or breathing techniques, placebo or no treatment. DATA
      COLLECTION AND ANALYSIS: Two reviewers applied the inclusion and exclusion
      criteria on masked publications independently. They assessed the trial quality
      independently. Only data from the first arm of crossover trials were included.
      MAIN RESULTS: The seven included trials involved six comparisons and a total of
      126 people. The trials were small and not generally of high quality. The results
      could not be combined as trials addressed different patient groups and outcomes.
      In most comparisons, bronchial hygiene physical therapy produced no significant
      effects on pulmonary function, apart from clearing sputum in chronic obstructive
      pulmonary disease and in bronchiectasis. An update search carried out in January
      2007 did not identify any new studies for inclusion. AUTHORS' CONCLUSIONS: There
      is not enough evidence to support or refute the use of bronchial hygiene physical
      therapy in people with chronic obstructive pulmonary disease and bronchiectasis.

PMID- 21735380
TI  - Exercise for preventing and treating osteoporosis in postmenopausal women.
AB  - BACKGROUND: Osteoporosis is a condition resulting in an increased risk of
      skeletal fractures due to a reduction in the density of bone tissue. Treatment of
      osteoporosis typically involves the use of pharmacological agents. In general it
      is thought that disuse (prolonged periods of inactivity) and unloading of the
      skeleton promotes reduced bone mass, whereas mechanical loading through exercise
      increases bone mass. OBJECTIVES: To examine the effectiveness of exercise
      interventions in preventing bone loss and fractures in postmenopausal women.
      SEARCH STRATEGY: During the update of this review we updated the original search
      strategy by searching up to December 2010 the following electronic databases: the
      Cochrane Musculoskeletal Group's Trials Register; the Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 12); MEDLINE;
      EMBASE; HealthSTAR; Sports Discus; CINAHL; PEDro; Web of Science; Controlled
      Clinical Trials; and AMED. We attempted to identify other studies by contacting
      experts, searching reference lists and searching trial registers. SELECTION
      CRITERIA: All randomised controlled trials (RCTs) that met our predetermined
      inclusion criteria. DATA COLLECTION AND ANALYSIS: Pairs of members of the review
      team extracted the data and assessed trial quality using predetermined forms. For
      dichotomous outcomes (fractures), we calculated risk ratios (RRs) using a fixed
      effect model. For continuous data, we calculated mean differences (MDs) of the
      percentage change from baseline. Where heterogeneity existed (determined by the
      I(2) statistic), we used a random-effects model. MAIN RESULTS: Forty-three RCTs
      (27 new in this update) with 4320 participants met the inclusion criteria. The
      most effective type of exercise intervention on bone mineral density (BMD) for
      the neck of femur appears to be non-weight bearing high force exercise such as
      progressive resistance strength training for the lower limbs (MD 1.03; 95%
      confidence interval (CI) 0.24 to 1.82). The most effective intervention for BMD
      at the spine was combination exercise programmes (MD 3.22; 95% CI 1.80 to 4.64)
      compared with control groups. Fractures and falls were reported as adverse events
      in some studies. There was no effect on numbers of fractures (odds ratio (OR)
      0.61; 95% CI 0.23 to 1.64). Overall, the quality of the reporting of studies in
      the meta-analyses was low, in particular in the areas of sequence generation,
      allocation concealment, blinding and loss to follow-up. AUTHORS' CONCLUSIONS: Our
      results suggest a relatively small statistically significant, but possibly
      important, effect of exercise on bone density compared with control groups.
      Exercise has the potential to be a safe and effective way to avert bone loss in
      postmenopausal women.

PMID- 21735381
TI  - Interventions for treating oral lichen planus.
AB  - BACKGROUND: Oral lichen planus (OLP) is a common chronic autoimmune disease
      associated with cell-mediated immunological dysfunction. Symptomatic OLP is
      painful and complete healing is rare. OBJECTIVES: To assess the effectiveness and
      safety of any form of therapy for symptomatic OLP. SEARCH STRATEGY: The following
      electronic databases were searched: the Cochrane Oral Health Group Trials
      Register (to 26 January 2011), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 26
      January 2011) and EMBASE via OVID (1980 to 26 January 2011). There were no
      restrictions regarding language or date of publication. SELECTION CRITERIA: All
      randomised controlled clinical trials (RCTs) of therapy for symptomatic OLP which
      compared treatment with a placebo or between treatments or no intervention were
      considered in this review. DATA COLLECTION AND ANALYSIS: The titles and abstracts
      of all reports identified were scanned independently by two review authors. All
      studies meeting the inclusion criteria were assessed for risk of bias and data
      were extracted. For dichotomous outcomes, the estimates of effects of an
      intervention were expressed as risk ratios (RR) together with 95% confidence
      intervals. For continuous outcomes, mean differences (MD) and 95% confidence
      intervals were used to summarise the data for each group. The statistical unit
      was the patient. Meta-analyses were done only with studies of similar comparisons
      reporting the same outcome measures. MAIN RESULTS: 28 trials were included in
      this review. Pain is the primary outcome of this review because it is the
      indication for treatment of OLP, and therefore this review indicates as
      effective, only those treatments which significantly reduce pain. Although
      topical steroids are considered first line treatment for symptomatic OLP, we
      identified no RCTs that compared steroids with placebo. There is no evidence from
      the three trials of pimecrolimus that this treatment is better than placebo in
      reducing pain from OLP. There is weak evidence from two trials, at unclear and
      high risk of bias respectively, that aloe vera may be associated with a reduction
      in pain compared to placebo, but it was not possible to pool the pain data from
      these trials. There is weak and unreliable evidence from two small trials, at
      high risk of bias, that cyclosporin may reduce pain and clinical signs of OLP,
      but meta-analysis of these trials was not possible.There were five trials that
      compared steroids with calcineurin inhibitors, each evaluating a different pair
      of interventions. There is no evidence from these trials that there is a
      difference between treatment with steroids compared to calcineurin inhibitors
      with regard to reducing pain associated with OLP. From six trials there is no
      evidence that any specific steroid therapy is more or less effective at reducing
      pain compared to another type or dose of steroid. AUTHORS' CONCLUSIONS: Although
      topical steroids are considered to be first line treatment, we identified no RCTs
      that compared steroids with placebo in patients with symptomatic OLP. From the
      trials in this review there is no evidence that one steroid is any more effective
      than another. There is weak evidence that aloe vera may reduce the pain of OLP
      and improve the clinical signs of disease compared to placebo. There is weak and
      unreliable evidence that cyclosporin may reduce pain and clinical signs of OLP.
      There is no evidence that other calcineurin inhibitors reduce pain compared to
      either steroids or placebo. From the 28 trials included in this systematic
      review, the wide range of interventions compared means there is insufficient
      evidence to support the effectiveness of any specific treatment as being
      superior.

PMID- 21735382
TI  - Interventions for preventing lower limb soft-tissue running injuries.
AB  - BACKGROUND: Overuse soft-tissue injuries occur frequently in runners. Stretching
      exercises, modification of training schedules, and the use of protective devices
      such as braces and insoles are often advocated for prevention. This is an update
      of a review first published in 2001. OBJECTIVES: To assess the effects of
      interventions for preventing lower limb soft-tissue running injuries. SEARCH
      STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group
      Specialised Register (March 2011); The Cochrane Library 2010, Issue 4; MEDLINE
      (1966 to January 2011); EMBASE (1980 to January 2011); and international trial
      registries (17 January 2011). SELECTION CRITERIA: Randomised or quasi-randomised
      trials evaluating interventions to prevent lower limb soft-tissue running
      injuries. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk
      of bias (relating to sequence generation, allocation concealment, blinding,
      incomplete outcome data) and extracted data. Data were adjusted for clustering if
      necessary and pooled using the fixed-effect model when appropriate. MAIN RESULTS:
      We included 25 trials (30,252 participants). Participants were military recruits
      (19 trials), runners from the general population (three trials), soccer referees
      (one trial), and prisoners (two trials). The interventions tested in the included
      trials fell into four main preventive strategies: exercises, modification of
      training schedules, use of orthoses, and footwear and socks. All 25 included
      trials were judged as 'unclear' or 'high' risk of bias for at least one of the
      four domains listed above.We found no evidence that stretching reduces lower limb
      soft-tissue injuries (6 trials; 5130 participants; risk ratio [RR] 0.85, 95%
      confidence interval [95% CI] 0.65 to 1.12). As with all non-significant results,
      this is compatible with either a reduction or an increase in soft-tissue
      injuries. We found no evidence to support a training regimen of conditioning
      exercises to improve strength, flexibility and coordination (one trial; 1020
      participants; RR 1.20, 95% CI 0.77 to 1.87).We found no evidence that a longer,
      more gradual increase in training reduces injuries in novice runners (one trial;
      486 participants; RR 1.02, 95% CI 0.72 to 1.45). There was some evidence from a
      poor quality trial that additional training resulted in a significant increase in
      the number of naval recruits with shin splints (one trial; 1670 participants; RR
      2.02, 95% CI 1.11 to 3.70). There was limited evidence that injuries were less
      frequent in prisoners when running duration (one trial; 69 participants; RR 0.41,
      95% CI 0.21 to 0.79) or frequency (one trial; 58 participants; RR 0.19, 95% CI
      0.06 to 0.66) were reduced.Patellofemoral braces appear to be effective for
      preventing anterior knee pain (two trials; 227 participants; RR 0.41, 95% CI 0.24
      to 0.67).Custom-made biomechanical insoles may be more effective than no insoles
      for reducing shin splints (medial tibial stress syndrome) in military recruits
      (one trial; 146 participants; RR 0.24, 95% CI 0.08 to 0.69).We found no evidence
      in military recruits that wearing running shoes based on foot shape, rather than
      standard running shoes, significantly reduced rate of running injuries (2 trials;
      5795 participants; Rate Ratio 1.03, 95% CI 0.93 to 1.14). AUTHORS' CONCLUSIONS:
      Overall, the evidence base for the effectiveness of interventions to reduce soft
      tissue injury after intensive running is very weak, with few trials at low risk
      of bias. More well-designed and reported RCTs are needed that test interventions
      in recreational and competitive runners.

PMID- 21735383
TI  - Community interventions for preventing smoking in young people.
AB  - BACKGROUND: Cigarette smoking is one of the leading causes of preventable death
      in the world. Decisions to smoke are often made within a broad social context and
      therefore community interventions using coordinated, multi-component programmes
      may be effective in influencing the smoking behaviour of young people.
      OBJECTIVES: To determine the effectiveness of multi-component community based
      interventions in influencing smoking behaviour, which includes preventing the
      uptake of smoking in young people. SEARCH STRATEGY: The Tobacco Addiction group's
      specialised register, Medline and other health, psychology and public policy
      electronic databases were searched, the bibliographies of identified studies were
      checked and raw data was requested from study authors. Searches were updated in
      August 2010. SELECTION CRITERIA: Randomized and non randomized controlled trials
      that assessed the effectiveness of multi-component community interventions
      compared to no intervention or to single component or school-based programmes
      only. Reported outcomes had to include smoking behaviour in young people under
      the age of 25 years. DATA COLLECTION AND ANALYSIS: Information relating to the
      characteristics and the content of community interventions, participants,
      outcomes and methods of the study was extracted by one reviewer and checked by a
      second. Studies were combined in a meta-analysis where possible and reported in
      narrative synthesis in text and table. MAIN RESULTS: Twenty-five studies were
      included in the review and sixty-eight studies did not meet all of the inclusion
      criteria. All studies used a controlled trial design, with fifteen using random
      allocation of schools or communities. One study reported a reduction in short
      term smoking prevalence (twelve months or less), while nine studies detected
      significant long-term effects. Two studies reported significantly lower smoking
      rates in the control population while the remaining thirteen studies showed no
      significant difference between groups. Improvements were seen in secondary
      outcomes for intentions to smoke in six out of eight studies, attitudes in five
      out of nine studies, perceptions in two out of six studies and knowledge in three
      out of six studies, while significant differences in favour of the control were
      seen in one of the nine studies assessing attitudes and one of six studies
      assessing perceptions. AUTHORS' CONCLUSIONS: There is some evidence to support
      the effectiveness of community interventions in reducing the uptake of smoking in
      young people, but the evidence is not strong and contains a number of
      methodological flaws.

PMID- 21735384
TI  - Beta2-agonists for acute bronchitis.
AB  - BACKGROUND: There are no clearly effective treatments for the cough of acute
      bronchitis. Beta2-agonists are often prescribed, perhaps because clinicians
      suspect many patients also have reversible airflow restriction contributing to
      the symptoms. OBJECTIVES: To determine whether beta2-agonists improve acute
      bronchitis symptoms in patients with no underlying pulmonary disease. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) 2011, issue 1 which contains the Acute Respiratory Infections Group's
      Specialised Register, MEDLINE (January 1966 to February week 1, 2011) and EMBASE
      (1974 to February 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs)
      in which patients (adults, or children over two years of age) with acute
      bronchitis or acute cough and without known pulmonary disease were allocated to
      beta2-agonist versus placebo, no treatment or alternative treatment. DATA
      COLLECTION AND ANALYSIS: Three review authors independently selected outcomes and
      extracted data while blinded to study results. Two review authors independently
      assessed each trial for risk of bias. We analysed trials in children and adults
      separately. MAIN RESULTS: Two trials in children (n = 109) with no evidence of
      airway obstruction did not find any benefits from oral beta2-agonists. Five
      trials in adults (n = 418) had mixed results but overall summary statistics did
      not reveal any significant benefits from oral (three trials) nor inhaled (two
      trials) beta2-agonists. There were no significant differences in daily cough
      scores nor in the percentage of adults still coughing after seven days (control
      group 73%; risk ratio (RR) 0.77, 95% confidence interval (CI) 0.54 to 1.09). in
      one trial, subgroups with evidence of airflow limitation had lower symptom scores
      if given beta2-agonists. The trials that noted quicker resolution of cough with
      beta2-agonists were those with a higher proportion of wheezing patients at
      baseline. Adults given beta2-agonists were more likely to report tremor,
      shakiness or nervousness (RR 7.94, 95% CI 1.17 to 53.94; number needed to treat
      to harm (NNTH) 2.3). AUTHORS' CONCLUSIONS: There is no evidence to support the
      use of beta2-agonists in children with acute cough who do not have evidence of
      airflow obstruction. There is also little evidence that the routine use of beta2
      agonists is helpful for adults with acute cough. These agents may reduce
      symptoms, including cough, in people with evidence of airflow obstruction.
      However, this potential benefit is not well-supported by the available data and
      must be weighed against the adverse effects associated with their use.

PMID- 21735385
TI  - Mechanical devices for urinary incontinence in women.
AB  - BACKGROUND: ncontinence can have a devastating effect on the lives of sufferers
      with significant economic implications. Non-surgical treatments such as pelvic
      floor muscle training and the use of mechanical devices are usually the first
      line of management, particularly when a woman does not want surgery or when she
      is considered unfit for surgery. Mechanical devices are inexpensive and do not
      compromise future surgical treatment. OBJECTIVES: To determine the effects of
      mechanical devices in the management of adult female urinary incontinence. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group Specialised Register
      (searched 23 June 2010), EMBASE (January 1947 to 2010 Week 24), CINAHL (January
      1982 to 11 June 2010) and the reference lists of relevant articles. SELECTION
      CRITERIA: All randomised or quasi-randomised controlled trials of mechanical
      devices in the management of adult female urinary incontinence determined by
      symptom, sign or urodynamic diagnosis. DATA COLLECTION AND ANALYSIS: The
      reviewers assessed the identified studies for eligibility and risk of bias and
      independently extracted data from the included studies. Data analysis was
      performed using RevMan software (version 5.0.25). MAIN RESULTS: One new trial was
      identified and included in this update bringing the total to seven trials
      involving 732 women. Two small trials compared a mechanical device with no
      treatment and although they suggested that use of a mechanical device might be
      better than no treatment, the evidence for this was inconclusive. Four trials
      compared one mechanical device with another. Quantitative synthesis of data from
      these trials was not possible because different mechanical devices were compared
      in each trial using different outcome measures. Data from the individual trials
      showed no clear difference between devices, but with wide confidence intervals.
      One new trial compared three groups: a mechanical device alone, behavioural
      therapy (pelvic floor muscle training) alone and behavioural therapy combined
      with a mechanical device. While at three months, there were more withdrawals from
      the device-only group, at 12 months group differences between the groups were not
      sustained on any measure. AUTHORS' CONCLUSIONS: The place of mechanical devices
      in the management of urinary incontinence remains in question. Currently there is
      little evidence from controlled trials on which to judge whether their use is
      better than no treatment and large well-conducted trials are required for
      clarification. There was also insufficient evidence in favour of one device over
      another and little evidence to compare mechanical devices with other forms of
      treatment.

PMID- 21735386
TI  - Exercise-based cardiac rehabilitation for coronary heart disease.
AB  - BACKGROUND: The burden of coronary heart disease (CHD) worldwide is one of great
      concern to patients and healthcare agencies alike. Exercise-based cardiac
      rehabilitation aims to restore patients with heart disease to health. OBJECTIVES:
      To determine the effectiveness of exercise-based cardiac rehabilitation (exercise
      training alone or in combination with psychosocial or educational interventions)
      on mortality, morbidity and health-related quality of life of patients with CHD.
      SEARCH STRATEGY: RCTs have been identified by searching CENTRAL, HTA, and DARE
      (using The Cochrane Library Issue 4, 2009), as well as MEDLINE (1950 to December
      2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), and
      Science Citation Index Expanded (1900 to December 2009). SELECTION CRITERIA: Men
      and women of all ages who have had myocardial infarction (MI), coronary artery
      bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA), or
      who have angina pectoris or coronary artery disease defined by angiography. DATA
      COLLECTION AND ANALYSIS: Studies were selected and data extracted independently
      by two reviewers. Authors were contacted where possible to obtain missing
      information. MAIN RESULTS: This systematic review has allowed analysis of 47
      studies randomising 10,794 patients to exercise-based cardiac rehabilitation or
      usual care. In medium to longer term (i.e. 12 or more months follow-up) exercise
      based cardiac rehabilitation reduced overall and cardiovascular mortality [RR
      0.87 (95% CI 0.75, 0.99) and 0.74 (95% CI 0.63, 0.87), respectively], and
      hospital admissions [RR 0.69 (95% CI 0.51, 0.93)] in the shorter term (< 12
      months follow-up) with no evidence of heterogeneity of effect across trials.
      Cardiac rehabilitation did not reduce the risk of total MI, CABG or PTCA. Given
      both the heterogeneity in outcome measures and methods of reporting findings, a
      meta-analysis was not undertaken for health-related quality of life. In seven out
      of 10 trials reporting health-related quality of life using validated measures
      was there evidence of a significantly higher level of quality of life with
      exercise-based cardiac rehabilitation than usual care. AUTHORS' CONCLUSIONS:
      Exercise-based cardiac rehabilitation is effective in reducing total and
      cardiovascular mortality (in medium to longer term studies) and hospital
      admissions (in shorter term studies) but not total MI or revascularisation (CABG
      or PTCA). Despite inclusion of more recent trials, the population studied in this
      review is still predominantly male, middle aged and low risk. Therefore, well
      designed, and adequately reported RCTs in groups of CHD patients more
      representative of usual clinical practice are still needed. These trials should
      include validated health-related quality of life outcome measures, need to
      explicitly report clinical events including hospital admission, and assess costs
      and cost-effectiveness.

PMID- 21735387
TI  - WITHDRAWN: Conjugate vaccines for preventing meningococcal C meningitis and
      septicaemia.
AB  - BACKGROUND: Meningococcal polysaccharide (MPLS) vaccines protect against
      Serogroup C disease, but do not produce an immune response in infants less than
      two years of age. This limitation can be overcome by linking C polysaccharide to
      carrier proteins ('conjugating'), to create meningococcal serogroup C conjugate
      (MCC) vaccines. In the absence of trial data, the immune response to vaccination
      has been considered to be a reasonable surrogate for vaccine protection.
      OBJECTIVES: To assess the immunogenicity, safety and efficacy of MCC vaccines for
      preventing meningitis and septicaemia. SEARCH STRATEGY: We searched the Cochrane
      Central Register Controlled Trials (CENTRAL) (The Cochrane Library 2005, issue
      3); MEDLINE (1966 to September, Week 1 2005); and EMBASE (1990 to June 2005) and
      references of studies. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      and controlled clinical trials (CCTs) in humans comparing MCC vaccines against a
      control vaccine or none. In the absence of any trials on vaccine efficacy,
      population-based observational studies about effectiveness were included. DATA
      COLLECTION AND ANALYSIS: Two authors independently screened the results of the
      literature searches, selected eligible studies, extracted the data and evaluated
      the quality of them. MAIN RESULTS: The studies showed that MCC vaccine was highly
      immunogenic in infants after two and three doses, in toddlers after one and two
      doses and in older age groups after one dose. In general higher titres were
      generated after MCC than after MPLS vaccines. Immunological hypo-responsiveness
      seen after repeated doses of MPLS vaccine may be overcome with MCC. Observational
      studies have documented a significant decline in meningococcal C disease in
      countries where MCC vaccines have been widely used. The timing of the
      vaccinations schedules, the specific conjugate used, and the vaccines given
      concomitantly or combined, may be important. AUTHORS' CONCLUSIONS: The MCC
      vaccine appears to be safe, immunogenic and able to induce immunological memory
      in all age groups. Observational studies strongly suggest that MCC is clinically
      effective.

PMID- 21735389
TI  - WITHDRAWN: Written individualised management plans for asthma in children and
      adults.
AB  - BACKGROUND: Non-adherence to treatment advice is a common phenomenon in asthma
      and may account for a significant proportion of the morbidity. Comprehensive care
      that includes asthma education, a written self-management plan and regular review
      has been shown to improve asthma outcomes, but the contribution of these
      components has not been established. OBJECTIVES: To determine whether the
      provision of a written asthma self-management plan increases adherence and
      improves outcome. SEARCH STRATEGY: We carried out a search on the Cochrane
      Airways Group trials register. There was no language restriction. The search of
      the databases used the following terms: action plan OR self OR self-care OR self
      manag* OR educ* AND adher* OR comply OR compli*. We contacted authors of included
      studies for any unpublished or on-going studies and bibliographies of all
      included studies and reviews were searched for further studies. The most recent
      search was carried out in June 2004. SELECTION CRITERIA: We only considered
      randomised controlled trials (RCTs) in patients with asthma. Participants must
      have been assigned to receive an individualised written asthma management plan
      (symptom or peak flow based) about the actions required for regular asthma
      management and/or the actions to take in the event of an asthma exacerbation.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality
      and abstracted data. MAIN RESULTS: Seven trials met the inclusion criteria. The
      written management plans were either peak flow or symptom based, which were
      compared against each other or compared to no written management plan. Reported
      outcomes included: medication adherence, hospitalisation, emergency department
      visits, oral corticosteroid use, lung function, days lost from school/work,
      unscheduled doctor visits and respiratory tract infections. There was no
      consistent evidence that written plans produced better patient outcomes than no
      written plan. For some outcomes, there appeared to be an advantage of one type of
      plan over the other, but there was no consistency - one type of plan was not
      consistently more effective than another. AUTHORS' CONCLUSIONS: The available
      trials are too small and the results too few and inconsistent to form any firm
      conclusions as to the contribution of written self management plans in the known
      beneficial effects of a comprehensive asthma care programme.

PMID- 21735390
TI  - Dressings for the prevention of surgical site infection.
AB  - BACKGROUND: Surgical wounds (incisions) heal by primary intention when the wound
      edges are brought together and secured - often with sutures, staples, clips or
      glue. Wound dressings, usually applied after wound closure, provide physical
      support, protection from bacterial contamination and absorb exudate. Surgical
      site infection (SSI) is a common complication of surgical wounds that may delay
      healing. OBJECTIVES: To evaluate the effects of wound dressings for preventing
      SSI in people with surgical wounds healing by primary intention. SEARCH STRATEGY:
      We searched the Cochrane Wounds Group Specialised Register (searched 10 May
      2011); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2011 Issue 2); Ovid MEDLINE (1950 to April Week 4 2011); Ovid MEDLINE (In
      Process & Other Non-Indexed Citations, May 9, 2011); Ovid EMBASE (1980 to 2011
      Week 18); EBSCO CINAHL (1982 to 6 May 2011). There were no restrictions based on
      language or date of publication. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing alternative wound dressings or wound dressings with leaving
      wounds exposed for postoperative management of surgical wounds healing by primary
      intention. DATA COLLECTION AND ANALYSIS: Two review authors performed study
      selection, risk of bias assessment and data extraction independently. MAIN
      RESULTS: Sixteen RCTs were included (2578 participants). All trials were at
      unclear or high risk of bias. Nine trials included people with wounds resulting
      from surgical procedures with a contamination classification of 'clean', two
      trials included people with wounds resulting from surgical procedures with a
      'clean/contaminated' contamination classification and the remaining trials
      evaluated people with wounds resulting from various surgical procedures with
      different contamination classifications. Two trials compared wound dressings with
      leaving wounds exposed. The remaining 14 trials compared two alternative dressing
      types. No evidence was identified to suggest that any dressing significantly
      reduced the risk of developing an SSI compared with leaving wounds exposed or
      compared with alternative dressings in people who had surgical wounds healing by
      secondary intention. AUTHORS' CONCLUSIONS: At present, there is no evidence to
      suggest that covering surgical wounds healing by primary intention with wound
      dressings reduces the risk of SSI or that any particular wound dressing is more
      effective than others in reducing the rates of SSI, improving scarring, pain
      control, patient acceptability or ease of dressing removal. Most trials in this
      review were small and of poor quality at high or unclear risk of bias. However,
      based on the current evidence, we conclude that decisions on wound dressing
      should be based on dressing costs and the symptom management properties offered
      by each dressing type e.g. exudate management.

PMID- 21735391
TI  - Deep versus shallow suction of endotracheal tubes in ventilated neonates and
      young infants.
AB  - BACKGROUND: Mechanical ventilation is commonly used in Neonatal Intensive Care
      Units to assist breathing in a variety of conditions. Mechanical ventilation is
      achieved through the placement of an endotracheal tube (ETT) which is left in
      situ. The ETT is suctioned to prevent a build-up of secretions and blockage of
      the airway. Methods of suctioning the endotracheal tube vary according to
      institutional practice and the individual clinician performing the task. The
      depth of suctioning is one of these variables. The catheter may be passed to the
      tip of the ETT or beyond the tip into the trachea or bronchi to facilitate
      removal of secretions. However, trauma to the lower airways may result from the
      suction catheter being passed into the airway beyond the tip of the endotracheal
      tube. OBJECTIVES: To compare the effectiveness and complications of deep
      (catheter passed beyond the tip of the ETT) versus shallow (catheter passed to
      length of ETT only) suctioning of the endotracheal tube in ventilated infants.
      SEARCH STRATEGY: In this first update the searches were expanded to the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, March 30), MEDLINE
      (from January 1966 to May 30 2011), CINAHL (from 1982 to May 30 2011) and EMBASE
      (1980 to May 2011) using text words and subject headings relevant to endotracheal
      suctioning. There were no language restrictions. SELECTION CRITERIA: Controlled
      trials using random or quasi-random allocation of neonates receiving ventilatory
      support via an endotracheal tube to either deep or shallow endotracheal
      suctioning. DATA COLLECTION AND ANALYSIS: The updated search resulted in 149
      potentially relevant references. Two of the studies from this search were
      identified as potentially relevant. We included one of the potentially relevant
      studies and the other was excluded because it did not fit the inclusion criteria.
      MAIN RESULTS: One small crossover trial (n = 27) of shallow versus deep
      suctioning met the criteria for inclusion in this review. The reported outcomes
      were oxygen saturation and heart rate, during and after suctioning. There were no
      significant differences when shallow and deep suctioning methods were compared.
      AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials
      concerning the benefits or risks of deep versus shallow suctioning of
      endotracheal tubes in ventilated neonates and infants. Further high quality
      research is required.

PMID- 21735392
TI  - Strategies for integrating primary health services in low- and middle-income
      countries at the point of delivery.
AB  - BACKGROUND: In some low- and middle-income countries, separate vertical
      programmes deliver specific life-saving interventions but can fragment services.
      Strategies to integrate services aim to bring together inputs, organisation, and
      delivery of particular functions to increase efficiency and people's access. We
      examined the evidence on the effectiveness of integration strategies at the point
      of delivery (sometimes termed 'linkages'), including integrated delivery of
      tuberculosis (TB), HIV/AIDS and reproductive health programmes. OBJECTIVES: To
      assess the effects of strategies to integrate primary health care services on
      healthcare delivery and health status in low- and middle-income countries. SEARCH
      STRATEGY: We searched The Cochrane Central Register of Controlled Trials
      (CENTRAL) 2010, Issue 3, part of the The Cochrane Library.
      www.thecochranelibrary.com, including the Cochrane Effective Practice and
      Organisation of Care Group Specialised Register (searched 15 September  2010);
      MEDLINE, Ovid (1950 to August Week 5 2010) (searched 10 September  2010); EMBASE,
      Ovid (1980 to 2010 Week 35) (searched 10 September  2010); CINAHL, EBSCO (1980 to
      present) (searched 20 September 2010); Sociological Abstracts, CSA Illumina (1952
      to current) (searched 10 September  2010); Social Services Abstracts, CSA
      Illumina (1979 to current) (searched 10 September  2010); POPLINE (1970 to
      current) (searched 10 September  2010); International Bibliography of the Social
      Sciences, Webspirs (1951 to current) (searched 01 July 2008); HealthStar (1975 to
      September 2005), Cab Health (1972 to 1999), and reference lists of articles. We
      also searched the World Health Organization (WHOLIS) library database,
      handsearched relevant WHO publications, and contacted experts in the field.
      SELECTION CRITERIA: Randomised controlled trials, non-randomised controlled
      trials, controlled before and after studies, and interrupted time series analyses
      of integration strategies, including strengthening linkages, in primary health
      care services. Health services in high-income countries, private public
      partnerships, and hospital inpatient care were excluded as were programmes
      promoting the integrated management of childhood illnesses. The main outcomes
      were indicators of healthcare delivery, user views, and health status. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      the risk of bias. The statistical results of individual studies are reported and
      summarised. MAIN RESULTS: Five randomised trials and four controlled before and
      after studies were included. The interventions were complex.Five studies added an
      additional component, or linked a new component, to an existing service, for
      example, adding family planning or HIV counselling and testing to routine
      services. The evidence from these studies indicated that adding on services
      probably increases service utilisation but probably does not improve health
      status outcomes, such as incident pregnancies.Four studies compared integrated
      services to single, special services. Based on the included studies, fully
      integrating sexually transmitted infection (STI) and family planning, and
      maternal and child health services into routine care as opposed to delivering
      them as special 'vertical' services may decrease utilisation, client knowledge of
      and satisfaction with the services and may not result in any difference in health
      outcomes, such as child survival. Integrating HIV prevention and control at
      facility and community level improved the effectiveness of certain services (STI
      treatment in males) but resulted in no difference in health seeking behaviour,
      STI incidence, or HIV incidence in the population. AUTHORS' CONCLUSIONS: There is
      some evidence that 'adding on' services (or linkages) may improve the utilisation
      and outputs of healthcare delivery. However, there is no evidence to date that a
      fuller form of integration improves healthcare delivery or health status.
      Available evidence suggests that full integration probably decreases the
      knowledge and utilisation of specific services and may not result in any
      improvements in health status. More rigorous studies of different strategies to
      promote integration over a wider range of services and settings are needed. These
      studies should include economic evaluation and the views of clients as clients'
      views will influence the uptake of integration strategies at the point of
      delivery and the effectiveness on community health of these strategies.

PMID- 21735388
TI  - Reduced or modified dietary fat for preventing cardiovascular disease.
AB  - BACKGROUND: Reduction and modification of dietary fats have differing effects on
      cardiovascular risk factors (such as serum cholesterol), but their effects on
      important health outcomes are less clear. OBJECTIVES: To assess the effect of
      reduction and/or modification of dietary fats on mortality, cardiovascular
      mortality, cardiovascular morbidity and individual outcomes including myocardial
      infarction, stroke and cancer diagnoses in randomised clinical trials of at least
      6 months duration. SEARCH STRATEGY: For this review update, the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched
      through to June 2010. References of Included studies and reviews were also
      checked. SELECTION CRITERIA: Trials fulfilled the following criteria: 1)
      randomised with appropriate control group, 2) intention to reduce or modify fat
      or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not
      multi factorial, 4) adult humans with or without cardiovascular disease, 5)
      intervention at least six months, 6) mortality or cardiovascular morbidity data
      available. DATA COLLECTION AND ANALYSIS: Participant numbers experiencing health
      outcomes in each arm were extracted independently in duplicate and random effects
      meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel
      plots were performed. MAIN RESULTS: This updated review suggested that reducing
      saturated fat by reducing and/or modifying dietary fat reduced the risk of
      cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons,
      65,508 participants of whom 7% had a cardiovascular event, I(2) 50%). Subgrouping
      suggested that this reduction in cardiovascular events was seen in studies of fat
      modification (not reduction - which related directly to the degree of effect on
      serum total and LDL cholesterol and triglycerides), of at least two years
      duration and in studies of men (not of women). There were no clear effects of
      dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790
      participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978
      participants). This did not alter with sub-grouping or sensitivity analysis.Few
      studies compared reduced with modified fat diets, so direct comparison was not
      possible. AUTHORS' CONCLUSIONS: The findings are suggestive of a small but
      potentially important reduction in cardiovascular risk on modification of dietary
      fat, but not reduction of total fat, in longer trials. Lifestyle advice to all
      those at risk of cardiovascular disease and to lower risk population groups,
      should continue to include permanent reduction of dietary saturated fat and
      partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

PMID- 21735393
TI  - Radioisotopes for metastatic bone pain.
AB  - BACKGROUND: This is an update of the review published in Issue 4, 2003. Bone
      metastasis cause severe pain as well as pathological fractures, hypercalcaemia
      and spinal cord compression. Treatment strategies currently available to relieve
      pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy,
      hormone therapy, radioisotopes and bisphosphonates. OBJECTIVES: To determine
      efficacy and safety of radioisotopes in patients with bone metastases to improve
      metastatic pain, decrease number of complications due to bone metastases and
      improve patient survival. SEARCH STRATEGY: We sought randomised controlled trials
      (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October
      2010. SELECTION CRITERIA: Studies selected had metastatic bone pain as a major
      outcome after treatment with a radioisotope, compared with placebo or another
      radioisotope. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of
      included studies by their sequence generation, allocation concealment, blinding
      of study participants, researchers and outcome assessors, and incomplete outcome
      data. Two review authors extracted data. We performed statistical analysis as an
      "available case" analysis, and calculated global estimates of effect using a
      random-effects model. We also performed an intention-to-treat (ITT) sensitivity
      analysis. MAIN RESULTS: This update includes 15 studies (1146 analyzed
      participants): four (325 participants) already included and 11 new (821
      participants). Only three studies had a low risk of bias. We observed a small
      benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32
      to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief
      (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight
      studies, 499 participants). There is no conclusive evidence to demonstrate that
      radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia
      and thrombocytopenia are secondary effects significantly associated with the
      administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to
      treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group
      (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when
      comparing Strontium-89 ((89)Sr) with Samarium-153 ((153)Sm), Rhenium-186
      ((186)Re) and Phosphorus-32 ((32)P). We observed no significant differences
      between treatments. Similarly, we observed no differences when we compared
      different doses of (153)Sm (0.5 versus 1.0 mCi). AUTHORS' CONCLUSIONS: This
      update adds new evidence on efficacy of radioisotopes versus placebo, (89)Sr
      compared with other radioisotopes, and dose-comparisons of (153)Sm and (188)Re.
      There is some evidence indicating that radioisotopes may provide complete
      reduction in pain over one to six months with no increase in analgesic use, but
      severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.

PMID- 21735394
TI  - Antiretrovirals for reducing the risk of mother-to-child transmission of HIV
      infection.
AB  - BACKGROUND: Antiretroviral drugs reduce viral replication and can reduce mother
      to-child transmission of HIV either by lowering plasma viral load in pregnant
      women or through post-exposure prophylaxis in their newborns. In rich countries,
      highly active antiretroviral therapy (HAART) which usually comprises three drugs,
      has reduced the mother-to-child transmission rates to around 1-2%, but HAART is
      not always available in low- and middle-income countries. In these countries,
      various simpler and less costly antiretroviral regimens have been offered to
      pregnant women or to their newborn babies, or to both. OBJECTIVES: To determine
      whether, and to what extent, antiretroviral regimens aimed at decreasing the risk
      of mother-to-child transmission of HIV infection achieve a clinically useful
      decrease in transmission risk, and what effect these interventions have on
      maternal and infant mortality and morbidity. SEARCH STRATEGY: We sought to
      identify all relevant studies regardless of language or publication status by
      searching the Cochrane HIV/AIDS Review Group Trials Register, The Cochrane
      Library, MEDLINE, EMBASE and AIDSearch and relevant conference abstracts. We also
      contacted research organizations and experts in the field for unpublished and
      ongoing studies. The original review search strategy was conducted in 2002 and
      updated in 2006 and again in 2009. SELECTION CRITERIA: Randomised controlled
      trials of any antiretroviral regimen aimed at decreasing the risk of mother-to
      child transmission of HIV infection compared with placebo or no treatment, or
      compared with another antiretroviral regimen. DATA COLLECTION AND ANALYSIS: Two
      authors independently selected relevant studies, extracted data and assessed
      trial quality. For the primary outcomes, we used survival analysis to estimate
      the probability of infants being infected with HIV (the observed proportion) at
      various specific time-points and calculated efficacy at a specific time as the
      relative reduction in the proportion infected. Efficacy, at a specific time, is
      defined as the preventive fraction in the exposed group compared to the reference
      group, which is the relative reduction in the proportion infected: 1-(Re/Rf). For
      those studies where efficacy and hence confidence intervals were not calculated,
      we calculated the approximate confidence intervals for the efficacy using
      recommended methods. For analysis of results that are not based on survival
      analyses we present the relative risk for each trial outcome based on the number
      randomised. No meta-analysis was conducted as no trial assessed identical drug
      regimens. MAIN RESULTS: Twenty-five trials including 18,901 participants with a
      median trial sample size of 627 ranging from 50 to 1,844 participants were
      included in this update. Twenty-two trials randomised mothers (18 pre-natally and
      four in labour) and followed up their infants, and three trials randomised
      infants. The first trial began in April 1991 and assessed zidovudine (ZDV) versus
      placebo and since then, the type, dosage and duration of drugs to be compared has
      been modified in each subsequent trial. We present the results stratified by
      regimen and type of feeding.Antiretrovirals versus placebo In breastfeeding
      populations, three trials found that:ZDV given to mothers from 36 to 38 weeks
      gestation, during labour and for 7 days after delivery significantly reduced HIV
      infection at 4-8 weeks (Efficacy 32.00%; 95% CI 1.50 to 62.50), 3 to 4 months
      (Efficacy 33.07%; 95% CI 5.57 to 60.57), 6 months (Efficacy 34.55%; 95% CI 9.05
      to 60.05), 12 months (Efficacy 34.31%; 95% CI 9.30 to 59.32) and 18 months
      (Efficacy 29.74%; 95% CI 2.73 to 56.75).ZDV given to mothers from 36 weeks
      gestation and during labour significantly reduced HIV infection at 4 to 8 weeks
      (Efficacy 43.78%; 95% CI 8.78 to 78.78) and 3 to 4 months (Efficacy 36.95%; 95%
      CI 2.94 to 70.96) but not at birth.ZDV plus lamivudine (3TC) given to mothers
      from 36 weeks gestation, during labour and for 7 days after delivery and to
      babies for the first 7 days after birth (PETRA 'regimen A') significantly reduced
      HIV infection (Efficacy 62.75%; 95% CI 40.76 to 84.74) and a combined endpoint of
      HIV infection or death (Efficacy 62.75 [, ]61.00%; 95% CI 40.76 to 84.74) at 4 to
      8 weeks but these effects were not sustained at 18 months.ZDV plus 3TC given to
      mothers from the start of labour until 7 days after delivery and to babies for
      the first 7 days after birth (PETRA 'regimen B') significantly reduced HIV
      infection (Efficacy 41.83%; 95% CI 12.82 to 70.84) and HIV infection or death at
      4 to 8 weeks (Efficacy 35.91%; 95% CI 8.41 to 63.41) but the effects were not
      sustained at 18 months.ZDV plus 3TC given to mothers during labour only (PETRA
      'regimen C') with no treatment to babies did not reduce the risk of HIV infection
      at either 4 to 8 weeks or 18 months.In non-breastfeeding populations, three
      trials found that:ZDV given to mothers from 14 to 34 weeks gestation and during
      labour and to babies for the first 6 weeks after birth significantly reduced HIV
      infection in babies at 18 months (Efficacy 66.22%; 95% CI 33.94 to 98.50).ZDV
      given to mothers from 36 weeks gestation and during labour with no treatment to
      babies ('Thai-CDC regimen') significantly reduced HIV infection at 4 to 8 weeks
      (Efficacy 50.26%; 95% CI 13.80 to 86.72) but not at birthZDV given to mothers
      from 38 weeks gestation and during labour with no treatment to babies did not
      influence HIV transmission at 6 months.Longer versus shorter regimens using the
      same antiretrovirals One trial in a breastfeeding population found that:ZDV given
      to mothers during labour and to their babies for the first 3 days after birth
      compared with ZDV given to mothers from 36 weeks and during labour (similar to
      'Thai-CDC') resulted in HIV infection rates that were not significantly different
      at birth, 4-8 weeks, 3 to 4 months, 6 months and 12 months.Three trials in non
      breastfeeding populations found that:ZDV given to mothers from 28 weeks gestation
      during labour and to infants for the first 3 days after birth compared with ZDV
      given to mothers from 35 weeks gestation through labour and to infants from birth
      to 6 weeks significantly reduced HIV infection rate at 6 months (Efficacy 45.35
      %; 95% CI 1.39 to 89.31) but compared with the same regimen ZDV given to mothers
      from 28 weeks gestation through labour and to infants from birth to 6 weeks did
      not result in a statistically significant difference in HIV infection at 6
      months. ZDV given to mothers from 35 weeks gestation during labour and to infants
      for the first 3 days after birth was considered ineffective for reducing
      transmission rates and this regimen was discontinued.An antenatal/intrapartum
      course of ZDV used for a median of 76 days compared with an antenatal/intrapartum
      ZDV regimen used for a median 28 days with no treatment to babies in either group
      did not result in HIV infection rates that were significantly different at birth
      and at 3 to 4 months.In a programme where mothers were routinely receiving ZDV in
      the third trimester of pregnancy and babies were receiving one week of ZDV
      therapy, a single dose of nevirapine (NVP) given to mothers in labour and to
      their babies soon after birth compared with a single dose of NVP given to mothers
      only resulted in HIV infection rates that were not significantly different at
      birth and 6 months. However the reduction in risk of HIV infection or death at 6
      months was marginally significant (Efficacy 45.00%; 95% CI -4.00 to
      94.00).Antiretroviral regimens using different drugs and durations of treatmentIn
      breastfeeding populations, three trials found that:A single dose of NVP given to
      mothers at the onset of labour plus a single dose of NVP given to their babies
      immediately after birth ('HIVNET 012 regimen') compared with ZDV given to mothers
      during labour and to their babies for a week after birth resulted in lower HIV
      infection rates at 4-8 weeks (Efficacy 41.00%; 95% CI 11.84 to 70.16), 3-4 months
      (Efficacy 38.91%; 95% CI 11.24 to 66.58), 12 months (Efficacy 35.98 [9.25,
      62.71]36.00%; 95% CI 8.56 to 63.44) and 18 months (Efficacy 39.15%; 95% CI 13.81
      to 64.49). In addition, the NVP regimen significantly reduced the risk of HIV
      infection or death at 4-8 weeks (Efficacy 41.74%; 95% CI 14.30 to 69.18), 3 to 4
      months (Efficacy 40.00%; 95% CI 14.34 to 65.66), 12 months (Efficacy 32.17%; 95%
      CI 8.51 to 55.83) and 18 months (Efficacy 32.57 [9.93, 55.21]33.00%; 95% CI 9.93
      to 55.21).The 'HIVNET 012 regimen' plus ZDV given to babies for 1 week after
      birth compared with the 'HIVNET 012 regimen' alone did not result in a
      statistically significant difference in HIV infection at 4 to 8 weeks.A single
      dose of NVP given to babies immediately after birth plus ZDV given to babies for
      1 week after birth compared with a single dose of NVP given to babies only
      significantly reduced the HIV infection rate at 4 to 8 weeks (Efficacy 36.79%;
      95% CI 3.57 to 70.01).Five trials in non-breastfeeding populations found that:In
      a population in which mothers were receiving 'standard' antiretroviral for HIV
      infection a single dose of NVP given to mothers in labour plus a single dose of
      NVP given to babies immediately after birth ('HIVNET 012 regimen') compared with
      placebo did not result in a statistically significant difference in HIV infection
      rates at birth and at 4 to 8 weeks.The 'Thai CDC regimen' compared with the
      'HIVNET 012 regimen' did not result in a significant difference in HIV infection
      at 4 to 8 weeks.A single dose of NVP given to babies immediately after birth
      compared to ZDV given to babies for the first 6 weeks after birth did not result
      in a significant difference in HIV infection rates at 4-8 weeks and 3 to 4
      months. (ABSTRACT TRUNCATED)

PMID- 21735395
TI  - Single, double or multiple-injection techniques for axillary brachial plexus
      block for hand, wrist or forearm surgery in adults.
AB  - BACKGROUND: Regional anaesthesia comprising axillary block of the brachial plexus
      is a common anaesthetic technique for distal upper limb surgery. This is an
      update of a review first published in 2006. OBJECTIVES: To compare the relative
      effects of single, double or multiple injections for axillary block of the
      brachial plexus for distal upper limb surgery. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library),
      MEDLINE, EMBASE and reference lists of trials. We contacted trial authors. The
      date of the last search was March 2011 (updated from March 2005). SELECTION
      CRITERIA: We included randomized controlled trials that compared double with
      single-injection techniques, multiple with single-injection techniques, or
      multiple with double-injection techniques for axillary block in adults undergoing
      surgery of the distal upper limb. We excluded trials using ultrasound-guided
      techniques. DATA COLLECTION AND ANALYSIS: We performed independent study
      selection, risk of bias assessment and data extraction. We undertook meta
      analysis. MAIN RESULTS: The 20 included trials involved a total of 2098
      participants who received regional anaesthesia for hand, wrist, forearm or elbow
      surgery. The trial design and conduct were generally adequate although several
      trials failed to monitor longer-term effects.Eight trials comparing double versus
      single injections showed a statistically significant decrease in primary
      anaesthesia failure (RR 0.51, 95% CI 0.30 to 0.85). Subgroup analysis by method
      of nerve location showed that the effect size was greater when neurostimulation
      was used rather than the transarterial technique.Seven trials comparing multiple
      with single injections showed a statistically significant decrease in primary
      anaesthesia failure (RR 0.28, 95% CI 0.16 to 0.48) and of incomplete motor block
      (RR 0.61, 95% CI 0.39 to 0.96) in the multiple injection group.Eleven trials
      comparing multiple with double injections showed a statistically significant
      decrease in primary anaesthesia failure (RR 0.28, 95% CI 0.20 to 0.40) and of
      incomplete motor block (RR 0.55, 95% CI 0.36 to 0.85) in the multiple injection
      group.Tourniquet pain was significantly reduced with multiple injections compared
      with double injections (RR 0.53, 95% CI 0.33 to 0.84). Otherwise, there were no
      statistically significant differences between groups in any of the three
      comparisons on secondary analgesia failure, complications and patient discomfort.
      The time for block performance was significantly shorter for single and double
      injections compared with multiple injections. AUTHORS' CONCLUSIONS: This review
      provides evidence that multiple injection techniques using nerve stimulation for
      axillary plexus block produce more effective anaesthesia than either double or
      single injection techniques. However, there was insufficient evidence for a
      significant difference in other outcomes, including safety.

PMID- 21735396
TI  - Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low
      birth weight infants.
AB  - BACKGROUND: Patent ductus arteriosus (PDA) complicates the clinical course of
      preterm infants and increases the risk of adverse outcomes. Indomethacin has been
      the standard treatment to close a PDA but is associated with renal,
      gastrointestinal and cerebral side-effects. Ibuprofen has less effect on blood
      flow velocity to important organs. OBJECTIVES: To determine the effectiveness and
      safety of prophylactic ibuprofen compared to placebo/no intervention in the
      prevention of PDA in preterm infants. SEARCH STRATEGY: Randomized controlled
      trials of prophylactic ibuprofen were identified by searching in The Cochrane
      Library, MEDLINE, CINAHL, EMBASE and trials registries in December 2010.
      SELECTION CRITERIA: Randomized or quasi-randomised controlled trials comparing
      ibuprofen with placebo/no intervention or other cyclo-oxygenase inhibitor drugs
      to prevent PDA in preterm and/or low birth weight infants. DATA COLLECTION AND
      ANALYSIS: Outcomes data including presence of PDA on day three, need for surgical
      ligation or rescue treatment with cyclo-oxygenase inhibitors, mortality,
      intraventricular haemorrhage (IVH), renal, pulmonary and gastrointestinal
      complications were extracted. Meta-analyses were performed and treatment
      estimates are reported as typical weighted mean difference, relative risk (RR),
      risk difference (RD) and, if statistically significant, number needed to treat to
      benefit (NNT) or number needed to treat to harm (NNH) along with their 95%
      confidence intervals (CI). MAIN RESULTS: In this update, seven studies (n = 931)
      comparing prophylactic ibuprofen with placebo/no intervention are included.
      Ibuprofen decreased the incidence of PDA on day three [typical RR 0.36 (95% CI
      0.29 to 0.46); typical RD -0.27 (95% CI -0.32 to -0.21); NNT 4 (95% CI 3 to 5)],
      decreased the need for rescue treatment with cyclo-oxygenase inhibitors and
      decreased the need for surgical ligation. Results from two studies administering
      oral ibuprofen had similar results, but showed an increased risk of
      gastrointestinal bleeding (NNH 4, 95% CI 2 to 17). In the control group the
      spontaneous closure rate was 58% by day three. Ibuprofen negatively affects renal
      function. No significant differences in mortality, IVH, chronic lung disease were
      found. AUTHORS' CONCLUSIONS: Prophylactic use of ibuprofen decreased the
      incidence of PDA, decreased the need for rescue treatment with cyclo-oxygenase
      inhibitors and decreased the need for surgical closure. In the control group, the
      PDA closed spontaneously by day three in 58% of the neonates. Prophylactic
      treatment exposes many infants to a drug that has concerning renal and
      gastrointestinal side effects without conferring any important short-term
      benefits and is not recommended. Until long-term follow-up results are published
      from the trials included in this updated review, no further trials of
      prophylactic ibuprofen are recommended.

PMID- 21735397
TI  - Day care versus in-patient surgery for age-related cataract.
AB  - BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness
      in the world with the majority of people who are blind from cataract found in the
      developing world. With the increased number of people with cataract there is an
      urgent need for cataract surgery to be made available as a day care procedure.
      OBJECTIVES: To provide reliable evidence for the safety, feasibility,
      effectiveness and cost-effectiveness of cataract extraction performed as day care
      versus in-patient procedure. SEARCH STRATEGY: We searched CENTRAL (which contains
      the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011,
      Issue 5), MEDLINE (January 1950 to May 2011), EMBASE (January 1980 to May 2011),
      Latin American and Caribbean Health Sciences Literature Database (LILACS)
      (January 1982 to May 2011), the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov).
      There were no date or language restrictions in the electronic searches for
      trials. The electronic databases were last searched on 23 May 2011. SELECTION
      CRITERIA: We included randomised controlled trials comparing day care and in
      patient surgery for age-related cataract. The primary outcome was the achievement
      of a satisfactory visual acuity six weeks after the operation. DATA COLLECTION
      AND ANALYSIS: Two authors independently assessed trial quality and extracted
      data. We contacted study authors for additional information. Adverse effects
      information was collected from the trials. MAIN RESULTS: We included two trials
      (conducted in Spain and USA), involving 1284 people. One trial reported
      statistically significant differences in early postoperative complication rates
      in the day care group, with an increased risk of increased intraocular pressure,
      which had no clinical relevance to visual outcomes four months postoperatively.
      The mean change in visual acuity (Snellen lines) of the operated eye four months
      postoperatively was 4.1 (standard deviation (SD) 2.3) for the day care group and
      4.1 (SD 2.2) for the in-patient group and not statistically significant. The four
      month postoperative mean change in quality of life score measured using the VF14
      showed minimal differences between the two groups. Costs were 20% more for the in
      patient group and this was attributed to higher costs for overnight stay. One
      study only reported hotel costs for the non-hospitalised participants making
      aggregation of data on costs impossible. AUTHORS' CONCLUSIONS: This review
      provides some evidence that there is a cost saving but no significant difference
      in outcome or risk of postoperative complications between day care and in-patient
      cataract surgery. This is based on one detailed and methodologically sound trial
      conducted in the developed world. The success, safety and cost-effectiveness of
      cataract surgery as a day care procedure appear to be acceptable. Future research
      may well focus on evidence provided by high quality clinical databases and
      registers which would enable clinicians and healthcare planners to agree clinical
      and social indications for in-patient care and so make better use of resources,
      by selecting day case surgery unless these criteria are met.

PMID- 21735398
TI  - Stretching to prevent or reduce muscle soreness after exercise.
AB  - BACKGROUND: Many people stretch before or after engaging in athletic activity.
      Usually the purpose is to reduce risk of injury, reduce soreness after exercise,
      or enhance athletic performance. This is an update of a Cochrane review first
      published in 2007. OBJECTIVES: The aim of this review was to determine effects of
      stretching before or after exercise on the development of delayed-onset muscle
      soreness. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma
      Group Specialised Register (to 10 August 2009), the Cochrane Central Register of
      Controlled Trials (2010, Issue 1), MEDLINE (1966 to 8th February 2010), EMBASE
      (1988 to 8th February 2010), CINAHL (1982 to 23rd February 2010), SPORTDiscus
      (1949 to 8th February 2010), PEDro (to 15th February 2010) and reference lists of
      articles. SELECTION CRITERIA: Eligible studies were randomised or quasi
      randomised studies of any pre-exercise or post-exercise stretching technique
      designed to prevent or treat delayed-onset muscle soreness (DOMS). For the
      studies to be included, the stretching had to be conducted soon before or soon
      after exercise and muscle soreness had to be assessed. DATA COLLECTION AND
      ANALYSIS: Risk of bias was assessed using The Cochrane Collaboration's 'Risk of
      bias' tool and quality of evidence was assessed using GRADE. Estimates of effects
      of stretching were converted to a common 100-point scale. Outcomes were pooled in
      fixed-effect meta-analyses. MAIN RESULTS: Twelve studies were included in the
      review. This update incorporated two new studies. One of the new trials was a
      large field-based trial that included 2377 participants, 1220 of whom were
      allocated stretching. All other 11 studies were small, with between 10 and 30
      participants receiving the stretch condition. Ten studies were laboratory-based
      and other two were field-based. All studies were exposed to either a moderate or
      high risk of bias. The quality of evidence was low to moderate.There was a high
      degree of consistency of results across studies. The pooled estimate showed that
      pre-exercise stretching reduced soreness at one day after exercise by, on
      average, half a point on a 100-point scale (mean difference -0.52, 95% CI -11.30
      to 10.26; 3 studies). Post-exercise stretching reduced soreness at one day after
      exercise by, on average, one point on a 100-point scale (mean difference -1.04,
      95% CI -6.88 to 4.79; 4 studies). Similar effects were evident between half a day
      and three days after exercise. One large study showed that stretching before and
      after exercise reduced peak soreness over a one week period by, on average, four
      points on a 100-point scale (mean difference -3.80, 95% CI -5.17 to -2.43). This
      effect, though statistically significant, is very small. AUTHORS' CONCLUSIONS:
      The evidence from randomised studies suggests that muscle stretching, whether
      conducted before, after, or before and after exercise, does not produce
      clinically important reductions in delayed-onset muscle soreness in healthy
      adults.

PMID- 21735399
TI  - Therapeutic interventions for Burkitt lymphoma in children.
AB  - BACKGROUND: Burkitt lymphoma (BL) is an important cancer found mostly in children
      but uncertainty remains as to the most effective form of management. In endemic
      areas, late-stage presentation as a result of delayed access to treatment
      compounds the situation. OBJECTIVES: To assess the evidence for chemotherapy,
      surgery, radiotherapy and immunotherapy in the treatment of children with endemic
      BL. SEARCH STRATEGY: We updated and re-ran the searches in the following
      electronic databases from the time of the first publication; the Cochrane
      Controlled Trials Register (CENTRAL) (Issue 1, 2011); MEDLINE (January 2011);
      EMBASE (January 2011); and the clinical trials registry (up to January 2011) to
      identify relevant trials. In addition, we also updated the search of the US
      clinical trials register for on-going and completed trials up to January 2011. We
      also updated the search terms and used the Cochrane filter for identifying
      randomised trials in MEDLINE. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) of any duration. We included studies conducted in
      children with a confirmed diagnosis of BL. We did not restrict studies by
      geographical location or by language of publication. We considered any
      therapeutic intervention. The primary outcome was overall survival. DATA
      COLLECTION AND ANALYSIS: Two review authors assessed studies for relevance. We
      assessed studies that met the entry criteria for study quality. We independently
      extracted data and entered the data into Review Manager (RevMan). In this update,
      two review authors independently assessed citations from the updated search and
      reviewed abstracts for relevance. MAIN RESULTS: We included one new study in this
      update. In total, 13 trials involving 1824 participants met the inclusion
      criteria for this review however, data in usable format were only available in 10
      trials (732 participants). Inadequate reporting of study methodology was a common
      feature of the trials preventing thorough assessment of study quality. We were
      unable to pool data for any of the outcomes due to the differences between the
      interventions assessed in the studies. Eight studies aimed to induce remission;
      overall survival did not differ significantly between treatment groups. Five
      studies aimed to maintain remission. In two out of three studies reporting
      survival, this was substantial but the difference was not statistically
      significant between treatment groups. Less aggressive treatment schedules appear
      to produce similar effects with less adverse event profiles. AUTHORS'
      CONCLUSIONS: This review notes a preference in more recent studies for less
      aggressive care options for treatment of BL. However, the evidence for the
      relative effectiveness of interventions to treat BL is not strong as studies were
      small, underpowered and prone to both systematic and random error. We included
      one additional trial without change of conclusions.

PMID- 21735400
TI  - Oral steroids for nasal polyps.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in The
      Cochrane Library in Issue 1, 2007.Benign nasal polyps are lesions that arise from
      the mucosa of the nasal cavity or one or more of the nasal sinuses. The
      presenting symptoms are nasal obstruction, watery anterior rhinorrhoea (excessive
      nasal secretions) or mucopurulent postnasal drip (or both), hyposmia and anosmia
      (reduced or absent sense of smell) with a concomitant alteration in taste and
      infrequently pain over the dorsum of the nose, forehead and cheeks. The main aim
      of treatment is to relieve these symptoms. The aetiology of polyps is uncertain,
      therefore treatment options differ, consisting of a combination of medical and
      surgical management. Medical therapy is mainly in the form of steroids,
      administered topically or systemically via the oral route. OBJECTIVES: To assess
      the effects of oral steroids in patients with multiple nasal polyps. SEARCH
      STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials
      Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed;
      EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts;
      ISRCTN and additional sources for published and unpublished trials. The date of
      the most recent search was 12 October 2010, following a previous search in April
      2006. SELECTION CRITERIA: Randomised controlled trials and controlled clinical
      trials comparing oral steroids with no intervention, or placebo, or comparing
      doses or schedules of oral steroids in patients with multiple nasal polyps. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed study quality. We
      contacted study authors for additional information. MAIN RESULTS: Three trials
      (166 patients) met our inclusion criteria and showed a short-term benefit of a
      short (two to four-week) course of oral steroids of variable doses and duration
      when compared to placebo. There was an objective reduction of polyp size and a
      subjective improvement of nasal symptoms and quality of life. However, due to the
      moderate to low quality of these trials it was not possible to quantify the
      overall size of this effect.There was no report of significant adverse effects of
      treatment with a short course of steroids. AUTHORS' CONCLUSIONS: The authors
      found three randomised controlled trials, albeit of moderate to poor quality,
      that suggest a short-term benefit of oral steroids in patients with multiple
      nasal polyps. To address the issue more thoroughly well-designed, prospective,
      randomised controlled trials are still needed.

PMID- 21735401
TI  - Steroidal contraceptives: effect on bone fractures in women.
AB  - BACKGROUND: Steroidal contraceptive use has been associated with changes in bone
      mineral density in women. Whether such changes increase the risk of fractures
      later in life is not clear. Osteoporosis is a major public health concern. Age
      related decline in bone mass increases the risk of fracture, especially of the
      spine, hip, and wrist. Concern about bone health influences the recommendation
      and use of these effective contraceptives globally. OBJECTIVES: To evaluate the
      effect of using hormonal contraceptives before menopause on the risk of fracture
      in women SEARCH STRATEGY: We searched for studies of fracture or bone health and
      hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well
      as ClinicalTrials.gov and ICTRP. We wrote to investigators to find additional
      trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) were considered
      if they examined fractures, bone mineral density (BMD), or bone turnover in women
      with hormonal contraceptive use prior to menopause. Interventions could include
      comparing a hormonal contraceptive with a placebo or another hormonal
      contraceptive or could compare providing a supplement versus a placebo. DATA
      COLLECTION AND ANALYSIS: We assessed all titles and abstracts identified through
      the literature searches. Mean differences were computed using the inverse
      variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR)
      was calculated. Both included the 95% confidence interval (CI) and used a fixed
      effect model. Due to different interventions, no trials could be combined for
      meta-analysis. MAIN RESULTS: Of the 16 RCTs we found, 2 used a placebo and 1 used
      a non-hormonal method as the comparison, while 13 compared two hormonal
      contraceptives. No trial had fracture as an outcome. Most measured BMD and
      several assessed bone turnover. Depot medroxyprogesterone acetate (DMPA) was
      associated with decreased bone mineral density. The placebo-controlled trials
      showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA
      plus placebo. Combination contraceptives did not appear to negatively affect bone
      health, but none were placebo-controlled. For implants, the single-rod
      etonogestrel group showed a greater BMD decrease versus the two-rod
      levonorgestrel group. However, results were not consistent across all implant
      comparisons. AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence
      fracture risk cannot be determined from existing information. Many trials had
      small numbers of participants and some had large losses to follow up. Health care
      providers and women should consider the costs and benefits of these effective
      contraceptives. For example, injectable contraceptives and implants provide
      effective, long-term birth control yet do not involve a daily regimen. Progestin
      only contraceptives are considered appropriate for women who should avoid
      estrogen due to medical conditions.

PMID- 21735402
TI  - Physical interventions to interrupt or reduce the spread of respiratory viruses.
AB  - BACKGROUND: Viral epidemics or pandemics of acute respiratory infections like
      influenza or severe acute respiratory syndrome pose a global threat. Antiviral
      drugs and vaccinations may be insufficient to prevent their spread. OBJECTIVES:
      To review the effectiveness of physical interventions to interrupt or reduce the
      spread of respiratory viruses. SEARCH STRATEGY: We searched The Cochrane Library,
      the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which
      includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE
      (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010),
      CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS
      (2008 to October 2010) and IMSEAR (2008 to October 2010). SELECTION CRITERIA: In
      this update, two review authors independently applied the inclusion criteria to
      all identified and retrieved articles and extracted data. We scanned 3775 titles,
      excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of
      67 studies. We included physical interventions (screening at entry ports,
      isolation, quarantine, social distancing, barriers, personal protection, hand
      hygiene) to prevent respiratory virus transmission. We included randomised
      controlled trials (RCTs), cohorts, case-controls, before-after and time series
      studies. DATA COLLECTION AND ANALYSIS: We used a standardised form to assess
      trial eligibility. We assessed RCTs by randomisation method, allocation
      generation, concealment, blinding and follow up. We assessed non-RCTs for
      potential confounders and classified them as low, medium and high risk of bias.
      MAIN RESULTS: We included 67 studies including randomised controlled trials and
      observational studies with a mixed risk of bias. A total number of participants
      is not included as the total would be made up of a heterogenous set of
      observations (participant people, observations on participants and countries
      (object of some studies)). The risk of bias for five RCTs and most cluster-RCTs
      was high. Observational studies were of mixed quality. Only case-control data
      were sufficiently homogeneous to allow meta-analysis. The highest quality cluster
      RCTs suggest respiratory virus spread can be prevented by hygienic measures, such
      as handwashing, especially around younger children. Benefit from reduced
      transmission from children to household members is broadly supported also in
      other study designs where the potential for confounding is greater. Nine case
      control studies suggested implementing transmission barriers, isolation and
      hygienic measures are effective at containing respiratory virus epidemics.
      Surgical masks or N95 respirators were the most consistent and comprehensive
      supportive measures. N95 respirators were non-inferior to simple surgical masks
      but more expensive, uncomfortable and irritating to skin. Adding virucidals or
      antiseptics to normal handwashing to decrease respiratory disease transmission
      remains uncertain. Global measures, such as screening at entry ports, led to a
      non-significant marginal delay in spread. There was limited evidence that social
      distancing was effective, especially if related to the risk of exposure. AUTHORS'
      CONCLUSIONS: Simple and low-cost interventions would be useful for reducing
      transmission of epidemic respiratory viruses. Routine long-term implementation of
      some measures assessed might be difficult without the threat of an epidemic.

PMID- 21735403
TI  - Comprehensive geriatric assessment for older adults admitted to hospital.
AB  - BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional,
      interdisciplinary diagnostic process to determine the medical, psychological and
      functional capabilities of a frail elderly person in order to develop a co
      ordinated and integrated plan for treatment and long-term follow up. OBJECTIVES:
      We sought to evaluate the effectiveness of CGA in hospital for older adults
      admitted as an emergency. SEARCH STRATEGY: We searched the Cochrane Effective
      Practice and Organisation of Care (EPOC) Group Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library), the Database of
      Abstracts of Reviews of Effects (DARE), MEDLINE, EMBASE, CINAHL and AARP Ageline,
      and handsearched high-yield journals. SELECTION CRITERIA: We searched for
      randomised controlled trials comparing CGA (whether by mobile teams or in
      designated wards) to usual care. DATA COLLECTION AND ANALYSIS: Two review authors
      initially assessed eligibility and trial quality and extracted published data.
      MAIN RESULTS: Twenty-two trials evaluating 10,315 participants in six countries
      were identified. Patients in receipt of CGA were more likely to be alive and in
      their own homes at up to six months (OR 1.25, 95% CI 1.11 to 1.42, P = 0.0002)
      and at the end of scheduled follow up (median 12 months) (OR 1.16, 95% CI 1.05 to
      1.28, P = 0.003) when compared to general medical care. In addition, patients
      were less likely to be institutionalised (OR 0.79, 95% CI 0.69 to 0.88, P <
      0.0001). They were less likely to suffer death or deterioration (OR 0.76, 95% CI
      0.64 to 0.90, P = 0.001), and were more likely to experience improved cognition
      in the CGA group (OR 1.11, 95% CI 0.20 to 2.01, P = 0.02). Subgroup interaction
      in the primary outcomes suggests that the effects of CGA are primarily the result
      of CGA wards. AUTHORS' CONCLUSIONS: Comprehensive geriatric assessment increases
      a patient's likelihood of being alive and in their own home at up to 12 months.

PMID- 21735404
TI  - Chinese herbal medicine in the treatment of ectopic pregnancy.
AB  - BACKGROUND: Traditionally Chinese herbal medicine (CHM) has been used widely in
      Chinese hospitals to treat ectopic pregnancy. Many studies have been published
      supporting its use but the evidence has not been systematically reviewed. This is
      and update of the review published in 2007. OBJECTIVES: To determine the
      effectiveness and safety of CHM in the treatment of ectopic pregnancy. SEARCH
      STRATEGY: Computerised databases (CENTRAL (The Cochrane Library), MEDLINE,
      EMBASE, Chinese Biomedical Database, China National Knowledge Infrastructure,
      VIP, Traditional Chinese Medicine Database System) were searched from their
      inception to November 2010 for relevant trials. SELECTION CRITERIA: Randomised
      controlled trials (RCT) on the use of CHM for the treatment of ectopic pregnancy.
      DATA COLLECTION AND ANALYSIS: Original authors of the identified studies were
      contacted to determine the trial design and identify authentic RCTs. Two review
      authors extracted and analysed the data. MAIN RESULTS: The search identified 281
      trials. Only two studies involving a total of 157 participants were confirmed to
      be authentic RCTs (Li 2004c; Zhao 2000). Both were of poor methodological quality
      with a high risk of conflicted interest and potential for bias in favour of the
      intervention. We could not reach a definitive conclusion from the results. The
      pooled result showed that adding a Western medicine to CHM resulted in a
      significantly higher treatment success rate than with CHM alone (RR 1.33, 95% CI
      1.08 to 1.63). When CHM plus Western medicine was compared to CHM alone for the
      time to disappearance of abdominal pain, again the results favoured the arm that
      included Western medicine (RR -2.09, 95% CI -4.14 to -0.04). Results were
      inconsistent for the time required for human chorionic gonadotropin (beta-hCG) to
      return to normal. One study favoured CHM plus Western medicine over Western
      medicine (with or without placebo) (MD -6.68, 95% CI -11.49 to -1.87); when CHM
      plus Western medicine was compared to CHM alone the results favoured the arm that
      included Western medicine (MD -8.12, 95% CI -10.89 to -5.53). AUTHORS'
      CONCLUSIONS: We have not found any well-designed trials investigating Chinese
      herbal medicines in the treatment of ectopic pregnancy. We cannot support or
      refute any CHM preparation for clinical use on the basis of evidence from
      randomised controlled trials.

PMID- 21735405
TI  - Insulin detemir versus insulin glargine for type 2 diabetes mellitus.
AB  - BACKGROUND: Chronically elevated blood glucose levels are associated with
      significant morbidity and mortality. Many diabetes patients will eventually
      require insulin treatment to maintain good glycaemic control. There are still
      uncertainties about the optimal insulin treatment regimens for type 2 diabetes,
      but the long-acting insulin analogues seem beneficial. Several reviews have
      compared either insulin detemir or insulin glargine to NPH insulin, but research
      directly comparing both insulin analogues is limited. OBJECTIVES: To assess the
      effects of insulin detemir and insulin glargine compared with each other in the
      treatment of type 2 diabetes mellitus. SEARCH STRATEGY: We searched MEDLINE,
      EMBASE, The Cochrane Library, online registries of ongoing trials and abstract
      books. Date of last search was January 2011. SELECTION CRITERIA: All randomised
      controlled trials comparing insulin detemir with insulin glargine with a duration
      of 12 weeks or longer were included. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected the studies and extracted the data. Pooling of studies by
      means of random-effects meta-analysis was performed. MAIN RESULTS: This review
      examined four trials lasting 24 to 52 weeks involving 2250 people randomised to
      either insulin detemir or glargine. Overall, risk of bias of the evaluated
      studies was high. Insulin glargine was dosed once-daily in the evening. Insulin
      detemir was initiated once-daily in the evening with the option of an additional
      dose in the morning in three studies and initiated twice-daily in one study. Of
      randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at
      the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c
      (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not
      differ statistically significantly between treatment groups.The results showed no
      significant differences in overall, nocturnal and severe hypoglycaemia between
      treatment groups.Insulin detemir was associated with less weight gain. Treatment
      with insulin glargine resulted in a lower daily basal insulin dose and a lower
      number of injection site reactions.There was no significant difference in the
      variability of FPG or glucose values in 24-hour profiles between treatment
      groups. It was not possible to draw conclusions on quality of life, costs or
      mortality. Only one trial reported results on health-related quality of life and
      showed no significant differences between treatment groups. AUTHORS' CONCLUSIONS:
      Our analyses suggest that there is no clinically relevant difference in efficacy
      or safety between insulin detemir and insulin glargine for targeting
      hyperglycaemia. However, to achieve the same glycaemic control insulin detemir
      was often injected twice-daily in a higher dose but with less weight gain, while
      insulin glargine was injected once-daily, with somewhat fewer injection site
      reactions.

PMID- 21735406
TI  - Tight control of mild-moderate pre-existing or non-proteinuric gestational
      hypertension.
AB  - BACKGROUND: The question of the target blood pressure in pregnant women with mild
      moderate hypertension continues to be an area of debate. OBJECTIVES: To compare
      tight versus very tight control of mild-moderate pre-existing or non-proteinuric
      gestational hypertension for improving outcomes SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011),
      CENTRAL (The Cochrane Library 2011, Issue 3), MEDLINE (January 1966 to March
      2011), and the metaRegister of Controlled Trials (31 March 2011). We handsearched
      citation lists of relevant publications, review articles, and included studies.
      SELECTION CRITERIA: Randomized controlled trials of tight versus very tight
      control in pregnant women with mild or moderate pre-existing or non-proteinuric
      gestational hypertension. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data. We expressed results as risk ratio
      (RR) or mean differences, together with their 95% confidence intervals (CI). MAIN
      RESULTS: We included two studies (256 participants) with mild-moderate pre
      existing or non-proteinuric gestational hypertension. There was no evidence of a
      difference between tight and very tight control groups regarding severe pre
      eclampsia (risk ratio (RR) 1.28, 95% CI 0.97 to 1.70; two trials, 256
      participants). More women in the tight group were hospitalized during their
      pregnancy (RR 2.53, 95% CI 1.14 to 5.63; one trial, 125 participants). There was
      no evidence of a difference in other outcome measures including fetal distress,
      IUGR, neonatal admission to a NICU, perinatal deaths, induction of labor and
      cesarean delivery between the tight and the very tight control groups.
      Gestational age at delivery had a non-significant mean difference (MD) of -0.15
      weeks between the tight and very tight control groups (MD -0.15, 95% CI -1.52 to
      1.21, random-effects, T2 = 0.75, I2 = 77%; two trials, 256 participants). The MD
      in birthweight between the tight and the very tight control group was not
      significant (MD -100.00 grams, 95% CI -363.69 to 163.69; one trial, 125
      participants). AUTHORS' CONCLUSIONS: For pregnant women with non-severe pre
      existing or non-proteinuric gestational hypertension, there is insufficient
      evidence to determine how tight control of hypertension should be achieved to
      improve maternal and fetal-neonatal outcomes.

PMID- 21735407
TI  - Hospital nurse staffing models and patient and staff-related outcomes.
AB  - BACKGROUND: Nurse staffing interventions have been introduced across countries in
      recent years in response to changing patient requirements, developments in
      patient care, and shortages of qualified nursing staff. These include changes in
      skill mix, grade mix or qualification mix, staffing levels, nursing shifts or
      nurses' work patterns. Nurse staffing has been closely linked to patient
      outcomes, organisational outcomes such as costs, and staff-related outcomes.
      OBJECTIVES: Our aim was to explore the effect of hospital nurse staffing models
      on patient and staff-related outcomes. SEARCH STRATEGY: We searched the following
      databases from inception through to May 2009: Cochrane/EPOC resources (DARE,
      CENTRAL, the EPOC Specialised Register), PubMed, EMBASE, CINAHL Plus, CAB Health,
      Virginia Henderson International Nursing Library, the Joanna Briggs Institute
      database, the British Library, international theses databases, as well as generic
      search engines. SELECTION CRITERIA: Randomised control trials, controlled
      clinical trials, controlled before and after studies and interrupted time series
      analyses of interventions relating to hospital nurse staffing models.
      Participants were patients and nursing staff working in hospital settings. We
      included any objective measure of patient or staff-related outcome. DATA
      COLLECTION AND ANALYSIS: Seven reviewers working in pairs independently extracted
      data from each potentially relevant study and assessed risk of bias. MAIN
      RESULTS: We identified 6,202 studies that were potentially relevant to our
      review. Following detailed examination of each study, we included 15 studies in
      the review. Despite the number of studies conducted on this topic, the quality of
      evidence overall was very limited. We found no evidence that the addition of
      specialist nurses to nursing staff reduces patient death rates, attendance at the
      emergency department, or readmission rates, but it is likely to result in shorter
      patient hospital stays, and reductions in pressure ulcers. The evidence in
      relation to the impact of replacing Registered Nurses with unqualified nursing
      assistants on patient outcomes is very limited. However, it is suggested that
      specialist support staff, such as dietary assistants, may have an important
      impact on patient outcomes. Self-scheduling and primary nursing may reduce staff
      turnover. The introduction of team midwifery (versus standard care) may reduce
      medical procedures in labour and result in a shorter length of stay without
      compromising maternal or perinatal safety. We found no eligible studies of
      educational interventions, grade mix interventions, or staffing levels and
      therefore we are unable to draw conclusions in relation to these interventions.
      AUTHORS' CONCLUSIONS: The findings suggest interventions relating to hospital
      nurse staffing models may improve some patient outcomes, particularly the
      addition of specialist nursing and specialist support roles to the nursing
      workforce. Interventions relating to hospital nurse staffing models may also
      improve staff-related outcomes, particularly the introduction of primary nursing
      and self-scheduling. However, these findings should be treated with extreme
      caution due to the limited evidence available from the research conducted to
      date.

PMID- 21735408
TI  - Oxytocin versus no treatment or delayed treatment for slow progress in the first
      stage of spontaneous labour.
AB  - BACKGROUND: Slow progress in the first stage of spontaneous labour is associated
      with an increased caesarean section rate and fetal and maternal morbidity.
      Oxytocin has long been advocated as a treatment for slow progress in labour but
      it is unclear to what extent it improves the outcomes for that labour and whether
      it actually reduces the caesarean section rate or maternal and fetal morbidity.
      This review will address the use of oxytocin and whether it improves the outcomes
      for women who are progressing slowly in labour compared to situations where it is
      not used or where its administration is delayed. OBJECTIVES: To determine if the
      use of oxytocin for the treatment of slow progress in the first stage of
      spontaneous labour is associated with a reduction in the incidence of caesarean
      sections, or maternal and fetal morbidity compared to situations where it is not
      used or where its administration is delayed. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2011) and
      bibliographies of relevant papers. SELECTION CRITERIA: Randomised controlled
      trials which compared oxytocin with either placebo, no treatment or delayed
      oxytocin in the active stage of spontaneous labour in low-risk women at term.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for
      inclusion, assessed risk of bias and extracted data. We sought additional
      information from trial authors. MAIN RESULTS: We included eight studies in the
      review involving a total of 1338 low-risk women in the first stage of spontaneous
      labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo
      or no treatment (three trials); 2) the early use of oxytocin versus its delayed
      use (five trials). There were no significant differences in the rates of
      caesarean section or instrumental vaginal delivery in either comparison. Early
      use of oxytocin resulted in an increase in uterine hyperstimulation associated
      with fetal heart changes. However, the early use of oxytocin versus its delayed
      use resulted in no significant differences in a range of neonatal and maternal
      outcomes. Use of early oxytocin resulted in a statistically significant reduction
      in the mean duration in labour of approximately two hours but did not increase
      the normal delivery rate. There was significant heterogeneity for this analysis
      and we carried out a random-effects meta-analysis; however, all of the trials are
      strongly in the same direction so it is reasonable to conclude that this is the
      true effect. We also performed a random-effects meta-analysis for the four other
      analyses which showed substantial heterogeneity in the review. AUTHORS'
      CONCLUSIONS: For women making slow progress in spontaneous labour, treatment with
      oxytocin as compared with no treatment or delayed oxytocin treatment did not
      result in any discernable difference in the number of caesarean sections
      performed. In addition there were no detectable adverse effects for mother or
      baby. The use of oxytocin was associated with a reduction in the time to delivery
      of approximately two hours which might be important to some women. However, if
      the primary goal of this treatment is to reduce caesarean section rates, then
      doctors and midwives may have to look for alternative options.

PMID- 21735409
TI  - Early versus Delayed Refeeding for Children with Acute Diarrhoea.
AB  - BACKGROUND: Acute diarrhoea is one of the principal causes of morbidity and
      mortality among children in low-income countries.  The cornerstone of treatment
      is oral rehydration therapy and dietary management.  However, there is a lack of
      data and studies on both the timing and type of feeding that should be adopted
      during the course of the illness. OBJECTIVES: To compare the efficacy and safety
      of early and late reintroduction of feeding in children with acute diarrhoea.
      SEARCH STRATEGY: In May 2011, we searched the Cochrane Infectious Diseases Group
      Specialized Register, CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE,
      EMBASE, LILACS, and mRCT. We also contacted researchers and organizations, and
      searched reference lists. SELECTION CRITERIA: Randomized controlled trials of
      early versus late refeeding among children less than 10 years old with acute
      diarrhoea.  Early refeeding was defined as within 12 hours of start of
      rehydration and late refeeding was defined as more than 12 hours after start of
      rehydration.  DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      the search results and the risk of bias, and extracted data. We present risk
      ratios for dichotomous outcomes and mean differences for continuous outcomes. We
      combined the results of the trials using meta-analysis when heterogeneity was not
      substantial. MAIN RESULTS: Twelve trials involving 1283 participants
      wereincluded; 1226 participants were used in the analysis (724 in the early
      refeeding group and 502 in the late refeeding group). Nine trials described their
      allocation sequence, but only two used concealed allocation. One trial reported
      single-blinding but did not clearly identify the person who was blinded. Early
      refeeding meant intake during or immediately after start of rehydration, while
      late refeeding meant intake only 20 hours to 48 hours after start of rehydration.
      Significant heterogeneity was noted in the data for the duration of diarrhoea.
      There was no significant difference between the two refeeding groups in the
      number of participants who needed unscheduled intravenous fluids (six trials with
      813 participants), who experienced episodes of vomiting (five trials with 466
      participants), and who developed persistent diarrhoea (four trials with 522
      participants). The mean length of hospital stay was also similar (two trials with
      246 participants). AUTHORS' CONCLUSIONS: There was no evidence that early
      refeeding increases the risk of unscheduled intravenous fluid use, episodes of
      vomiting, and development of persistent diarrhoea. No conclusion could be made
      regarding the duration of diarrhoea.

PMID- 21735410
TI  - Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction
      complicated by cardiogenic shock.
AB  - BACKGROUND: Intra-aortic balloon pump counterpulsation (IABP) is currently the
      most commonly used mechanical assist device for patients with cardiogenic shock
      due to acute myocardial infarction.Although there is only limited evidence by
      randomised controlled trials, the current guidelines of the American Heart
      Association/American College of Cardiology and the European Society of Cardiology
      strongly recommend the use of the intra-aortic balloon counterpulsation in
      patients with infarction-related cardiogenic shock on the basis of
      pathophysiological considerations as also non-randomised trials and registry
      data.    OBJECTIVES: To determine the effect of IABP versus non-IABP or other
      assist devices guideline compliant standard therapy, in terms of efficacy and
      safety, on mortality and morbidity in patients with acute myocardial infarction
      complicated by cardiogenic shock. SEARCH STRATEGY: Searches of CENTRAL, MEDLINE
      and EMBASE, LILACS, IndMed and KoreaMed, registers of ongoing trials and
      proceedings of conferences were conducted in January 2010, unrestricted by date.
      Reference lists were scanned and experts in the field contacted to obtain further
      information. No language restrictions were applied. SELECTION CRITERIA:
      Randomised controlled trials on patients with myocardial infarction complicated
      by cardiogenic shock. DATA COLLECTION AND ANALYSIS: Data collection and analysis
      were performed according to a published protocol. Individual patient data were
      provided for five trials and merged with aggregate data. Summary statistics for
      the primary endpoints were hazard ratios (HR's) and odds ratios with 95%
      confidence intervals (CI). MAIN RESULTS: Six eligible and two ongoing studies
      were identified from a total of 1410 references. Three compared IABP to standard
      treatment and three to percutaneous left assist devices (LVAD). Data from a total
      of 190 patients with acute myocardial infarction and cardiogenic shock were
      included in the meta-analysis: 105 patients were treated with IABP and 85
      patients served as controls. 40 patients were treated without assisting devices
      and 45 patients with LVAD. HR's for all-cause 30-day mortality of 1.04 (95% CI
      0.62 to 1.73) provides no evidence for a survival benefit. While differences in
      survival were comparable in patients treated with IABP, with and without LVAD,
      haemodynamics and incidences of device related complications show heterogeneous
      results. AUTHORS' CONCLUSIONS: Available evidence suggests that IABP may have a
      beneficial effect on the haemodynamics, however there is no convincing randomised
      data to support the use of IABP in infarct related cardiogenic shock.

PMID- 21735411
TI  - Vitamin D supplementation for prevention of mortality in adults.
AB  - BACKGROUND: The available evidence on vitamin D and mortality is inconclusive.
      OBJECTIVES: To assess the beneficial and harmful effects of vitamin D for
      prevention of mortality in adults. SEARCH STRATEGY: We searched The Cochrane
      Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and
      Conference Proceedings Citation Index-Science (to January 2011). We scanned
      bibliographies of relevant publications and asked experts and pharmaceutical
      companies for additional trials. SELECTION CRITERIA: We included randomised
      trials that compared vitamin D at any dose, duration, and route of administration
      versus placebo or no intervention. Vitamin D could have been administered as
      supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2)
      (ergocalciferol)) or an active form of vitamin D (1alpha-hydroxyvitamin D
      (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND
      ANALYSIS: Six authors extracted data independently. Random-effects and fixed
      effect model meta-analyses were conducted. For dichotomous outcomes, we
      calculated the risk ratios (RR). To account for trials with zero events, meta
      analyses of dichotomous data were repeated using risk differences (RD) and
      empirical continuity corrections. Risk of bias was considered in order to
      minimise risk of systematic errors. Trial sequential analyses were conducted to
      minimise the risk of random errors. MAIN RESULTS: Fifty randomised trials with
      94,148 participants provided data for the mortality analyses. Most trials
      included elderly women (older than 70 years). Vitamin D was administered for a
      median of two years. More than one half of the trials had a low risk of bias.
      Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI)
      0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed
      separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI
      0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2),
      alfacalcidol, or calcitriol did not. Trial sequential analysis supported our
      finding regarding vitamin D(3), corresponding to 161 individuals treated to
      prevent one additional death. Vitamin D(3) combined with calcium increased the
      risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol
      and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to
      8.68, I(2) = 17%). Data on health-related quality of life and health economics
      were inconclusive. AUTHORS' CONCLUSIONS: Vitamin D in the form of vitamin D(3)
      seems to decrease mortality in predominantly elderly women who are mainly in
      institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had
      no statistically significant effect on mortality. Vitamin D(3) combined with
      calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol
      significantly increased hypercalcaemia.

PMID- 21735412
TI  - Lifestyle changes in women with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) affects 4% to 18% of reproductive
      aged women and is associated with reproductive, metabolic and psychological
      dysfunction. Obesity worsens the presentation of PCOS and weight management
      (weight loss, maintenance or prevention of excess weight gain) is proposed as an
      initial treatment strategy, best achieved through lifestyle changes incorporating
      diet, exercise and behavioural interventions. OBJECTIVES: To assess the
      effectiveness of lifestyle treatment in improving reproductive, anthropometric
      (weight and body composition), metabolic and quality of life factors in PCOS.
      SEARCH STRATEGY: Electronic databases (Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL, AMED)
      (date of last search 7/9/2010), controlled trials register, conference abstracts,
      relevant journals, reference lists of relevant papers and reviews and grey
      literature databases, with no language restrictions applied. SELECTION CRITERIA:
      Randomised controlled trials comparing lifestyle treatment (diet, exercise,
      behavioural or combined treatments) to minimal or no treatment in women with
      PCOS. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials,
      assessed methodological quality and risk of bias and extracted data. MAIN
      RESULTS: Six studies were included with n=164 participants. Three studies
      compared physical activity to minimal dietary and behavioural advice or no
      advice. Three studies compared combined dietary, exercise and behavioural
      interventions to minimal intervention. Risk of bias varied with 4/6 having
      adequate sequence generation and clinician or outcome assessor blinding and 3/6
      having adequate allocation concealment, complete outcome data and being free of
      selective reporting.  There were no studies assessing the fertility primary
      outcomes of pregnancy, live birth and miscarriage and no data for meta-analysis
      on ovulation or menstrual regularity. Lifestyle intervention provided benefits
      when compared to minimal treatment for secondary reproductive, anthropometric and
      reproductive outcomes. These included endpoint values for total testosterone
      (mean difference (MD) -0.27 nmol/L, 95% confidence interval (CI) -0.46 to -0.09,
      P = 0.004), hirsutism or excess hair growth by the Ferriman-Gallwey score (MD 
      1.19, 95% CI -2.35 to -0.03, P = 0.04), weight (MD -3.47 kg, 95% CI -4.94 to 
      2.00, P < 0.00001), waist circumference (MD -1.95 cm, 95% CI -3.34 to -0.57, P =
      0.006) and fasting insulin (MD -2.02 uU/mL, 95% CI -3.28 to -0.77, P = 0.002).
      There was no evidence of effect of lifestyle for body mass index, free androgen
      index, sex hormone binding globulin, glucose or cholesterol levels; and no data
      for quality of life, patient satisfaction or acne. AUTHORS' CONCLUSIONS:
      Lifestyle intervention improves body composition, hyperandrogenism (high male
      hormones and clinical effects) and insulin resistance in women with PCOS. There
      was no evidence of effect for lifestyle intervention on improving glucose
      tolerance or lipid profiles and no literature assessing clinical reproductive
      outcomes, quality of life and treatment satisfaction.

PMID- 21735413
TI  - Mind-body interventions during pregnancy for preventing or treating women's
      anxiety.
AB  - BACKGROUND: Anxiety during pregnancy is a common problem. Anxiety and stress
      could have consequences on the course of the pregnancy and the later development
      of the child. Anxiety responds well to treatments such as cognitive behavioral
      therapy and/or medication. Non-pharmacological interventions such as mind-body
      interventions, known to decrease anxiety in several clinical situations, might be
      offered for treating and preventing anxiety during pregnancy. OBJECTIVES: To
      assess the benefits of mind-body interventions during pregnancy in preventing or
      treating women's anxiety and in influencing perinatal outcomes. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30
      November 2010), MEDLINE (1950 to 30 November 2010), EMBASE (1974 to 30 November
      2010), the National Center for Complementary and Alternative Medicine (NCCAM) (1
      December 2010), ClinicalTrials.gov (December 2010) and Current Controlled Trials
      (1 December 2010), searched the reference lists of selected studies and contacted
      professionals and authors in the field. SELECTION CRITERIA: Randomized controlled
      trials, involving pregnant women of any age at any time from conception to one
      month after birth, comparing mind-body interventions with a control group. Mind
      body interventions include: autogenic training, biofeedback, hypnotherapy,
      imagery, meditation, prayer, auto-suggestion, tai-chi and yoga. Control group
      includes: standard care, other pharmacological or non-pharmacological
      interventions, other types of mind-body interventions or no treatment at all.
      DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials
      for inclusion all assessed risk of bias for each included study. We extracted
      data independently using an agreed form and checked it for accuracy. MAIN
      RESULTS: We included eight trials (556 participants), evaluating hypnotherapy
      (one trial), imagery (five trials), autogenic training (one trial) and yoga (one
      trial). Due to the small number of studies per intervention and to the diversity
      of outcome measurements, we performed no meta-analysis, and have reported results
      individually for each study. Compared with usual care, in one study (133 women),
      imagery may have a positive effect on anxiety during labor decreasing anxiety at
      the early and middle stages of labor (MD -1.46; 95% CI -2.43 to -0.49; one study,
      133 women) and (MD -1.24; 95% CI -2.18 to -0.30). Another study showed that
      imagery had a positive effect on anxiety and depression in the immediate
      postpartum period. Autogenic training might be effective for decreasing women's
      anxiety before delivering. AUTHORS' CONCLUSIONS: Mind-body interventions might
      benefit women's anxiety during pregnancy. Based on individual studies, there is
      some but no strong evidence for the effectiveness of mind-body interventions for
      the management of anxiety during pregnancy. The main limitations of the studies
      were the lack of blinding and insufficient details on the methods used for
      randomization.

PMID- 21735414
TI  - Fluid restriction and prophylactic indomethacin versus prophylactic indomethacin
      alone for prevention of morbidity and mortality in extremely low birth weight
      infants.
AB  - BACKGROUND: Although survival of extremely low birth weight (ELBW) infants has
      dramatically improved over the last decades, the rate of bronchopulmonary
      dysplasia (BPD) has not changed. The use of indomethacin prophylaxis in ELBW
      infants results in improved short-term outcomes with no effect on long-term
      outcomes. The addition of fluid restriction to the indomethacin prophylaxis
      policy could result in a reduction of BPD and improve long-term survival without
      neurosensory impairment at eighteen months corrected age. OBJECTIVES: To
      determine the effect of a policy of fluid restriction compared with a policy of
      no fluid restriction on morbidity and mortality in ELBW infants receiving
      indomethacin prophylaxis. SEARCH STRATEGY: We used the standard search strategy
      for the Cochrane Neonatal Review Group (CNRG). This included searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library
      2010, Issue 1), MEDLINE (1966 to December 2010), and EMBASE (1980 to December
      2010). Additional searches included conference proceedings, references in
      articles and unpublished data. SELECTION CRITERIA: We planned to include all
      randomized or quasi-randomized trials that compared fluid restriction and
      indomethacin prophylaxis versus indomethacin prophylaxis alone in ELBW infants.
      DATA COLLECTION AND ANALYSIS: If we had identified any eligible studies, we would
      have assessed the methodological quality of the trials using the standard methods
      of the CNRG. We planned to use Review Manager 5 software for statistical
      analysis. MAIN RESULTS: We did not identify any eligible trials. AUTHORS'
      CONCLUSIONS: We found no randomized controlled trials to investigate the possible
      interaction between fluid restriction and indomethacin prophylaxis versus
      indomethacin prophylaxis alone in ELBW infants. A well-designed randomized trial
      is needed to address this question.

PMID- 21735415
TI  - Self-management education for cystic fibrosis.
AB  - BACKGROUND: Self-management education may help patients with cystic fibrosis and
      their families to choose, monitor and adjust treatment requirements for their
      illness, and also to manage the effects of illness on their lives. Although self
      management education interventions have been developed for cystic fibrosis, no
      previous systematic review of the evidence of effectiveness of these
      interventions has been conducted. OBJECTIVES: To assess the effects of self
      management education interventions on improving health outcomes for patients with
      cystic fibrosis and their caregivers SEARCH STRATEGY: We searched the Cochrane
      Cystic Fibrosis and Genetic Disorders Group Trials Register (date of the last
      search: 23 February 2011).We also searched databases through EBSCO (CINAHL;
      Psychological and Behavioural Sciences Collection; PsychInfo; SocINDEX) and
      Elsevier (EMBASE) and handsearched relevant journals and conference proceedings
      (date of the last searches: 30th March 2011). SELECTION CRITERIA: Randomised
      controlled trials, quasi-randomised controlled trials or controlled clinical
      trials comparing different types of self-management education for cystic fibrosis
      or comparing self-management education with standard care or no intervention.
      DATA COLLECTION AND ANALYSIS: Two authors assessed trial eligibility and risk of
      bias. Three authors extracted data. MAIN RESULTS: Four trials (involving a total
      of 269 participants) were included. The participants were children with cystic
      fibrosis and their parents or caregivers in three trials and adults with cystic
      fibrosis in one trial. The trials compared four different self-management
      education interventions versus standard treatment: (1) a training programme for
      managing cystic fibrosis in general; (2) education specific to aerosol and airway
      clearance treatments; (3) disease-specific nutrition education; and (4) general
      and disease-specific nutrition education. Training children to manage cystic
      fibrosis in general had no statistically significant effects on weight after six
      to eight weeks, mean difference -7.74 lb (95% confidence interval -35.18 to
      19.70). General and disease-specific nutrition education for adults had no
      statistically significant effects on: pulmonary function (forced expiratory
      volume at one second), mean difference -5.00 % (95% confidence interval -18.10 to
      8.10) at six months and mean difference -5.50 % (95% confidence interval -18.46
      to 7.46) at 12 months; or weight, mean difference - 0.70 kg (95% confidence
      interval -6.58 to 5.18) at six months and mean difference -0.70 kg (95%
      confidence interval -6.62 to 5.22) at 12 months; or dietary fat intake scores,
      mean difference 1.60 (85% confidence interval -2.90 to 6.10) at six months and
      mean difference 0.20 (95% confidence interval -4.08 to 4.48) at 12 months. There
      is some limited evidence to suggest that self-management education may improve
      knowledge in patients with cystic fibrosis but not in parents or caregivers.
      There is also some limited evidence to suggest that self-management education may
      result in positively changing a small number of behaviours in both patients and
      caregivers. AUTHORS' CONCLUSIONS: The available evidence from this review is of
      insufficient quantity and quality to draw any firm conclusions about the effects
      of self-management education for cystic fibrosis. Further trials are needed to
      investigate the effects of self-management education on a range of clinical and
      behavioural outcomes in children, adolescents and adults with cystic fibrosis and
      their caregivers.

PMID- 21735416
TI  - Sublingual immunotherapy for treating allergic conjunctivitis.
AB  - BACKGROUND: Allergic ocular symptoms, although frequently trivialised, are common
      and represent an important comorbidity of allergic rhinitis. Sublingual
      Immunotherapy (SLIT) is an effective and well-tolerated treatment for allergic
      rhinitis, but its effects on symptoms of ocular allergy have not been well
      established. OBJECTIVES: To evaluate the efficacy of SLIT compared with placebo
      for reductions in ocular symptoms, topical ocular medication requirements and
      conjunctival immediate allergen sensitivity. SEARCH STRATEGY: We searched CENTRAL
      (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane
      Library 2011, Issue 1), MEDLINE (January 1950 to January 2011), EMBASE (January
      1980 to January 2011), Latin American and Caribbean Literature on Health Sciences
      (LILACS) (January 1982 to January 2011), Web of Science (January 1970 to January
      2011), Biosis Previews, (January 1979 to January 2011), the metaRegister of
      Controlled Trials (mRCT) (www.controlled-trials.com) (January 2011),
      ClinicalTrials.gov (www.clinicaltrials.gov) (January 2011), the Australian New
      Zealand Clinical Trials Registry (ANZCTR) (www.actr.org.au) (July 2010), SCOPUS
      (November 2008) and the UK Clinical Trials Gateway (January 2010). There were no
      language or date restrictions in the search for trials. All electronic databases
      except for SCOPUS, the UK Clinical Trials Gateway and ANZCTR were last searched
      on 19 January 2011. SELECTION CRITERIA: Randomised controlled trials (RCTs),
      double-masked and placebo controlled, which evaluated the efficacy of SLIT in
      patients with symptoms of allergic rhinoconjunctivitis (ARC) or allergic
      conjunctivitis (AC). DATA COLLECTION AND ANALYSIS: The primary outcome was the
      total ocular symptom scores. Secondary endpoints included individual ocular
      symptom scores (such as itchy eyes, red eyes, watery eyes, swollen eyes), ocular
      medication scores (eye drops) and conjunctival immediate allergen sensitivity
      (CIAS). Data were analysed and reported as standardised mean differences (SMDs)
      using Review Manager software. MAIN RESULTS: Forty-two trials (n = 3958 total
      participants; n= 2011 SLIT and n = 1947 placebo) had available data to evaluate
      the efficacy of SLIT on AC and were included in the meta-analyses. Heterogeneity
      among studies (I(2) statistic) was around 50% or below for all endpoints.
      Sublingual immunotherapy induced a significant reduction in both total ocular
      symptom scores (SMD -0.41; 95% confidence interval (CI) -0.53 to -0.28; P <
      0.00001; I(2) = 59%) and individual ocular symptom scores for red eyes (SMD 
      0.33; 95% CI -0.45 to -0.22; P < 0.00001; I(2) = 27%), itchy eyes (SMD -0.31; 95%
      CI -0.42 to -0.20; P < 0.00001; I(2) = 46%) and watery eyes (SMD -0.23; 95% CI 
      0.34 to -0.11; P < 0.0001; I(2) = 42%) compared to placebo. Those participants
      having active treatment showed an increase in the threshold dose for the
      conjunctival allergen provocation test (SMD 0.35; 95% CI 0.00 to 0.69; P = 0.05;
      I(2) = 43%). No significant reduction was observed in ocular eye drops use (SMD 
      0.10; 95% CI -0.22 to 0.03; P = 0.13; I(2) = 34%). AUTHORS' CONCLUSIONS: Overall,
      SLIT is moderately effective in reducing total and individual ocular symptom
      scores in participants with ARC and AC. There were however some concerns about
      the overall quality of the evidence-base, this relating to inadequate
      descriptions of allocation concealment in some studies, statistical heterogeneity
      and the possibility of publication bias. There is a need for further large
      rigorously designed studies that study long-term effectiveness after
      discontinuation of treatment and establish the cost-effectiveness of SLIT.

PMID- 21735417
TI  - Telehealthcare for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disease of
      irreversible airways obstruction in which patients often suffer exacerbations.
      Sometimes these exacerbations need hospital care: telehealthcare has the
      potential to reduce admission to hospital when used to administer care to the
      pateint from within their own home. OBJECTIVES: To review the effectiveness of
      telehealthcare for COPD compared with usual face-to-face care. SEARCH STRATEGY:
      We searched the Cochrane Airways Group Specialised Register, which is derived
      from systematic searches of the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO; last searched January
      2010. SELECTION CRITERIA: We selected randomised controlled trials which assessed
      telehealthcare, defined as follows: healthcare at a distance, involving the
      communication of data from the patient to the health carer, usually a doctor or
      nurse, who then processes the information and responds with feedback regarding
      the management of the illness. The primary outcomes considered were: number of
      exacerbations, quality of life as recorded by the St George's Respiratory
      Questionnaire, hospitalisations, emergency department visits and deaths. DATA
      COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion
      and extracted data. We combined data into forest plots using fixed-effects
      modelling as heterogeneity was low (I(2) < 40%). MAIN RESULTS: Ten trials met the
      inclusion criteria. Telehealthcare was assessed as part of a complex
      intervention, including nurse case management and other interventions.
      Telehealthcare was associated with a clinically significant increase in quality
      of life in two trials with 253 participants (mean difference -6.57 (95%
      confidence interval (CI) -13.62 to 0.48); minimum clinically significant
      difference is a change of -4.0), but the confidence interval was wide.
      Telehealthcare showed a significant reduction in the number of patients with one
      or more emergency department attendances over 12 months; odds ratio (OR) 0.27
      (95% CI 0.11 to 0.66) in three trials with 449 participants, and the OR of having
      one or more admissions to hospital over 12 months was 0.46 (95% CI 0.33 to 0.65)
      in six trials with 604 participants. There was no significant difference in the
      OR for deaths over 12 months for the telehealthcare group as compared to the
      usual care group in three trials with 503 participants; OR 1.05 (95% CI 0.63 to
      1.75). AUTHORS' CONCLUSIONS: Telehealthcare in COPD appears to have a possible
      impact on the quality of life of patients and the number of times patients attend
      the emergency department and the hospital. However, further research is needed to
      clarify precisely its role since the trials included telehealthcare as part of
      more complex packages.

PMID- 21735418
TI  - Oral rinses, mouthwashes and sprays for improving recovery following
      tonsillectomy.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in The
      Cochrane Library in Issue 1, 2010.Tonsillectomy is the surgical removal of
      lymphoid tissue, the palatine tonsil, which is located at the back of the throat.
      It is still commonly performed for patients who have recurrent bouts of acute
      tonsillitis. Although tonsillectomy is considered a fairly minor procedure, pain
      and bleeding are two of the most common complications; either may delay recovery
      and can on occasion lead to hospital readmission. Postoperative tonsillectomy
      medication should provide an adequate reduction in morbidity while minimising
      side effects, therefore topical agents would seem to be an ideal, safe option. A
      number of mouthwashes and topical sprays are available which offer pain relief or
      can help to reduce bleeding in the immediate postoperative period. OBJECTIVES: To
      assess the effects of oral rinses, mouthwashes and sprays in improving recovery
      following tonsillectomy. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and
      Throat Disorders Group Trials Register; the Cochrane Central Register of
      Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS
      Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for
      published and unpublished trials. The date of the most recent search was 22 April
      2011. SELECTION CRITERIA: We included randomised controlled trials in which
      mouthwashes, used pre- and postoperatively, have been compared with placebo. DATA
      COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion,
      assessed the risk of bias and extracted data independently. MAIN RESULTS: We
      included six trials (528 participants; 397 children and 131 adults). The period
      of follow up ranged from 24 hours to two weeks. Few of the trials provided
      reliable data for the pre-specified primary outcomes and none for the secondary
      outcomes. Lidocaine spray appeared to be more effective than saline spray at
      reducing the severity of pain but only until the third postoperative day. A small
      number of participants experienced a burning or stinging sensation with
      benzydamine spray but not sufficient to discontinue usage. AUTHORS' CONCLUSIONS:
      The risk of bias was high in most of the included trials and poor reporting
      quality and inadequate data did not permit comprehensive and reliable conclusions
      to be made. Future trials should be well-constructed and pay more attention to
      the methods used to assess outcomes, the timing of the assessments, and the
      quality of reporting and subsequent analysis of the data.

PMID- 21735419
TI  - Anticonvulsants for tinnitus.
AB  - BACKGROUND: Tinnitus is the perception of sound or noise in the absence of an
      external or internal acoustic stimulation. It is a common and potentially
      distressing symptom for which no adequate therapy exists. OBJECTIVES: To assess
      the effectiveness of anticonvulsants in patients with chronic tinnitus. SEARCH
      STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group
      Specialised Register, CENTRAL (2010, Issue 2), MEDLINE, EMBASE, bibliographies
      and additional sources for published and unpublished trials. The date of the most
      recent search was 26 May 2010. SELECTION CRITERIA: We selected randomised
      controlled trials in patients with chronic tinnitus comparing orally administered
      anticonvulsants with placebo. The primary outcome was improvement in tinnitus
      measured with validated questionnaires. Secondary outcomes were improvement in
      tinnitus measured with self-assessment scores, improvement in global well-being
      or accompanying symptoms, and adverse drug effects. DATA COLLECTION AND ANALYSIS:
      Three authors assessed risk of bias and extracted data independently. MAIN
      RESULTS: Seven trials (453 patients) were included in this review. These studies
      investigated four different anticonvulsants: gabapentin, carbamazepine,
      lamotrigine and flunarizine. The risk of bias of most studies was 'high' or
      'unclear'. Three studies included a validated questionnaire (primary outcome).
      None of them showed a significant positive effect of anticonvulsants. One study
      showed a significant negative effect of gabapentin compared to placebo with an
      increase in Tinnitus Questionnaire (TQ) score of 18.4 points (standardised mean
      difference (SMD) 0.82, 95% confidence interval (CI) 0.07 to 1.58). A second study
      showed a positive, non-significant effect of gabapentin with a difference
      compared to placebo of 2.4 points on the Tinnitus Handicap Inventory (THI) (SMD 
      0.11, 95% CI -0.48 to 0.25). When the data from these two studies are pooled no
      effect of gabapentin is found (SMD 0.07, 95% CI -0.26 to 0.40). A third study
      reported no differences on the THI after treatment with gabapentin compared to
      placebo (exact numbers could not be extracted from the article).A meta-analysis
      of 'any positive effect' (yes versus no) based on a self-assessment score
      (secondary outcome) showed a small favourable effect of anticonvulsants (RD 14%,
      95% CI 6% to 22%). A meta-analysis of 'near or total eradication of tinnitus
      annoyance' showed no effect of anticonvulsants (risk difference (RD) 4%, 95% CI 
      2% to 11%). Side effects of the anticonvulsants used were experienced by 18% of
      patients. AUTHORS' CONCLUSIONS: Current evidence regarding the effectiveness of
      anticonvulsants in patients with tinnitus has significant risk of bias. There is
      no evidence from studies performed so far to show that anticonvulsants have a
      large positive effect in the treatment of tinnitus but a small effect (of
      doubtful clinical significance) has been demonstrated.

PMID- 21735420
TI  - Antidepressants for the treatment of abdominal pain-related functional
      gastrointestinal disorders in children and adolescents.
AB  - BACKGROUND: Abdominal pain-related functional gastrointestinal disorders (FGIDs)
      are among the most common medical problems in paediatric medicine. Frequently,
      physicians prescribe antidepressants as a second-line treatment for children and
      adolescents with FGIDs. To date, the evidence on the benefits and harms of
      antidepressants for the treatment of abdominal pain-related FGIDs has not been
      assessed systematically. OBJECTIVES: The primary objectives were to conduct a
      systematic review to evaluate the efficacy and safety of antidepressants for the
      treatment of abdominal pain-related FGIDs in children and adolescents. SEARCH
      STRATEGY: We searched The Cochrane Library, PubMed, EMBASE, IPA, CINAHL,
      PsycINFO, ISI Web of Science, Biosis Previews and the International Clinical
      Trials Registry Platform of the World Health Organization with appropriate
      filters (from inception to January 31, 2011). SELECTION CRITERIA: For efficacy we
      included double-blind, randomised controlled trials (RCTs) of antidepressants for
      treatment of abdominal pain-related FGIDs in children and adolescents 18 years or
      younger. Open-label and uncontrolled experimental studies, as well as
      observational studies were eligible for the assessment of harms. The minimum
      study duration was 4 weeks. The minimum study size was 30 participants. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed all abstracts and
      full text articles, and rated the risk of bias for included studies. Data were
      extracted independently by one author and checked for accuracy by another author.
      Data were analysed using RevMan 5. MAIN RESULTS: Two RCTs (123 participants),
      both using amitriptyline, met the pre-specified inclusion criteria. These studies
      provided mixed findings on the efficacy of amitriptyline for the treatment of
      abdominal pain-related FGIDs. The larger, publicly-funded study reported no
      statistically significant difference in efficacy between amitriptyline and
      placebo in 90 children and adolescents with FGIDs after 4 weeks of treatment. On
      intention-to-treat (ITT)- analysis, 59% of the children reported feeling better
      in the amitriptyline group compared with 53% in the placebo group (RR 1.12; 95%
      CI: 0.77 to 1.63; P = 0.54). The risk of bias for this study was rated as low.The
      second RCT enrolled 33 adolescents with irritable bowel syndrome. Patients
      receiving amitriptyline experienced greater improvements in the primary outcome,
      overall quality of life, at weeks 6, 10, and 13 compared with those on placebo
      (P= 0.019, 0.004, and 0.013, respectively). No effect estimates were calculated
      for the quality of life outcome because mean quality of life scores and standard
      deviations were not reported. For most secondary outcomes no statistically
      significant differences between amitriptyline and placebo could be detected. The
      risk of bias for this study was rated as unclear for most items. However, it was
      rated as high for other bias due to multiple testing. The results of this study
      should be interpreted with caution due to the small number of patients and
      multiple testing.The larger study reported mild adverse events including fatigue,
      rash and headache and dizziness. On ITT analysis, 4% of the amitriptyline group
      experienced at least one adverse event compared to 2% of the placebo group. There
      was no statistically significant difference in the proportion of patients who
      experienced at least one adverse event (RR 1.91; 95% CI 0.18 to 20.35; P = 0.59).
      The smaller study reported no adverse events. The methods of adverse effects
      assessment was poorly reported in both studies and no clear conclusions on the
      risks of harms of amitriptyline can be drawn. AUTHORS' CONCLUSIONS: Clinicians
      must be aware that for the majority of antidepressant medications no evidence
      exists that supports their use for the treatment of abdominal pain-related FGIDs
      in children and adolescents. The existing randomised controlled evidence is
      limited to studies on amitriptyline and revealed no statistically significant
      differences between amitriptyline and placebo for most efficacy outcomes.
      Amitriptyline does not appear to provide any benefit for the treatment of FGIDs
      in children and adolescents. Studies in children with depressive disorders have
      shown that antidepressants can lead to substantial, sometimes life-threatening
      adverse effects. Until better evidence evolves, clinicians should weigh the
      potential benefits of antidepressant treatment against known risks of
      antidepressants in paediatric patients.

PMID- 21735421
TI  - Optical coherence tomography (OCT) for detection of macular oedema in patients
      with diabetic retinopathy.
AB  - BACKGROUND: Diabetic macular oedema (DMO) is a thickening of the central retina,
      or the macula, and is associated with long-term visual loss in people with
      diabetic retinopathy (DR). Clinically significant macular oedema (CSMO) is the
      most severe form of DMO. Almost 30 years ago, the Early Treatment Diabetic
      Retinopathy Study (ETDRS) found that CSMO, diagnosed by means of stereoscopic
      fundus photography, leads to moderate visual loss in one of four people within
      three years. It also showed that grid or focal laser photocoagulation to the
      macula halves this risk. Recently, intravitreal injection of antiangiogenic drugs
      has been investigated to try to improve vision in people with macular oedema due
      to DR.Optical coherence tomography (OCT) is based on optical reflectivity and is
      able to image retinal thickness and structure producing cross-sectional and three
      dimensional images of the central retina. It is already widely used because it
      provides objective and quantitative assessment of macular oedema unlike the
      subjectivity of fundus biomicroscopic assessment, which is routinely used by
      ophthalmologists instead of photography. Optical coherence tomography is also
      used for quantitative follow up of the effects of treatment of CSMO.
      Disadvantages of using OCT are the cost to purchase it and the need for trained
      personnel to perform the examinations. OBJECTIVES: To determine the diagnostic
      accuracy of OCT for detecting macular oedema in people with DR. A secondary
      objective is to compare the diagnostic accuracy by study-specific
      characteristics, such as factors related to methodology, patients or OCT. SEARCH
      STRATEGY: We searched the Cochrane Database of Systematic Reviews (CDSR), the
      Database of Abstracts of Reviews of Effects (DARE), the Health Technology
      Assessment Database (HTA) and the NHS Economic Evaluation Database (NHSEED) (The
      Cochrane Library 2011, Issue 5), MEDLINE (January 1950 to May 2011), EMBASE
      (January 1950 to May 2011), ISI Web of Science (January 1970 to May 2011), BIOSIS
      Previews (January 1969 to May 2011), MEDION and the Aggressive Research
      Intelligence Facility database (ARIF). There were no date or language
      restrictions in the electronic search for trials. The electronic databases were
      last searched on 16 May 2011. We checked bibliographies of relevant studies for
      additional references. SELECTION CRITERIA: We selected studies that assessed the
      diagnostic accuracy of any OCT model for detecting DMO or CSMO in patients with
      DR who were referred to eye clinics. Diabetic macular oedema and CSMO were
      diagnosed by means of fundus biomicroscopy by ophthalmologists or
      stereophotography by ophthalmologists or other trained personnel. DATA COLLECTION
      AND ANALYSIS: Three authors independently extracted data on study characteristics
      and measures of accuracy. We assessed data using random-effects hierarchical sROC
      meta-analysis models. MAIN RESULTS: Nine studies (768 participants, 1325 eyes)
      were included. Prevalence of CSMO was 19% to 65% (median 50%). Study quality was
      good for half the QUADAS items, whereas unclear or inadequate quality was found
      in some studies regarding selection criteria, index and reference test masking
      (blinding), availability of clinical information, uninterpretable results and
      withdrawals. There was a specific 'unit of analysis' issue because both eyes of
      the majority of participants were included in the analyses as if they were
      independent.Central CSMO was the target condition in all but one study and thus
      our results cannot be applied to non-central CSMO. In eight studies providing
      data on CSMO (697 participants, 1241 eyes), pooled sensitivity was 0.78 (95%
      confidence interval (CI) 0.72 to 0.83) and specificity was 0.86 (95% CI 0.76 to
      0.93). The median central retinal thickness cut-off we selected for data
      extraction was 250 um (range 230 um to 300 um).Data from three studies reporting
      accuracy for detection of DMO (180 participants, 343 eyes) were not pooled.
      Sensitivities and specificities were about 0.80 in two studies and were both 1.00
      in the third study. AUTHORS' CONCLUSIONS: Central retinal thickness measured with
      OCT cannot be used as a stand-alone test to diagnose the central type of CSMO and
      decide on the use of laser photocoagulation in patients who are referred to
      retina clinics. In fact, there is a substantial disagreement of OCT with the
      ETDRS definition of CSMO based on clinical examination. Some researchers have
      observed that OCT can detect macular thickening earlier than clinical
      examination, but also found that such cases did not necessarily progress to CSMO
      and need photocoagulation.Care should be taken in applying the conclusions of
      this review to other test-treatment pathways. In fact, OCT will become an
      essential tool to manage antiangiogenic therapy, an expanding therapeutic option
      for patients with macular oedema due to DR, because OCT is a component of the
      diagnostic algorithms of studies on this new treatment.

PMID- 21735422
TI  - Rapid diagnostic tests for diagnosing uncomplicated P. falciparum malaria in
      endemic countries.
AB  - BACKGROUND: Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use
      antibodies to detect either HRP-2 antigen or pLDH antigen, and can improve access
      to diagnostics in developing countries. OBJECTIVES: To assess the diagnostic
      accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in
      endemic areas who present to ambulatory healthcare facilities with symptoms
      suggestive of malaria by type and brand. SEARCH STRATEGY: We undertook a
      comprehensive search of the following databases: Cochrane Infectious Diseases
      Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web
      of Knowledge; African Index Medicus; LILACS; IndMED; to January 14, 2010.
      SELECTION CRITERIA: Studies comparing RDTs with a reference standard (microscopy
      or polymerase chain reaction) in blood samples from a random or consecutive
      series of patients attending ambulatory health facilities with symptoms
      suggestive of malaria in P. falciparum endemic areas. DATA COLLECTION AND
      ANALYSIS: For each study, a standard set of data was extracted independently by
      two authors, using a tailored data extraction form. Comparisons were grouped
      hierarchically by target antigen, and type and brand of RDT, and combined in meta
      analysis where appropriate. MAIN RESULTS: We identified 74 unique studies as
      eligible for this review and categorized them according to the antigens they
      detected. Types 1 to 3 include HRP-2 (from P. falciparum) either by itself or
      with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by
      itself or with other antigens. In comparisons with microscopy, we identified 71
      evaluations of Type 1 tests, eight evaluations of Type 2 tests and five
      evaluations of Type 3 tests. In meta-analyses, average sensitivities and
      specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for
      Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests,
      and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests,
      respectively. Overall for HRP-2, the meta-analytical average sensitivity and
      specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%),
      respectively. For pLDH antibody-based RDTs verified with microscopy, we
      identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In
      meta-analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%)
      and average specificity was 98.7% (96.9% to 99.5%). For Type 5 tests, average
      sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5%
      to 99.1%). Overall for pLDH, the meta-analytical average sensitivity and
      specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%),
      respectively. For both categories of test, there was substantial heterogeneity in
      study results. Quality of the microscopy reference standard could only be
      assessed in 40% of studies due to inadequate reporting, but results did not seem
      to be influenced by the reporting quality.Overall, HRP-2 antibody-based tests
      (such as the Type 1 tests) tended to be more sensitive and were significantly
      less specific than pLDH-based tests (such as the Type 4 tests). If the point
      estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of
      1000 patients where 30% of those presenting with symptoms have P. falciparum,
      Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number
      of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and
      nine with Type 4 tests. AUTHORS' CONCLUSIONS: The sensitivity and specificity of
      all RDTs is such that they can replace or extend the access of diagnostic
      services for uncomplicated P. falciparum malaria. HRP-2 antibody types may be
      more sensitive but are less specific than pLDH antibody-based tests, but the
      differences are small. The HRP-2 antigen persists even after effective treatment
      and so is not useful for detecting treatment failures. 

PMID- 21735423
TI  - Interventions for improving coverage of child immunization in low- and middle
      income countries.
AB  - BACKGROUND: Immunization coverage remains low, particularly in low- and middle
      income countries (LMIC), despite its proven effectiveness in reducing the burden
      of childhood infectious diseases. A Cochrane review has shown that patient
      reminder recall is effective in improving coverage of immunization but
      technologies to support this strategy are lacking in LMIC. OBJECTIVES: To
      evaluate the effectiveness of intervention strategies to boost and sustain high
      childhood immunization coverage in LMIC. SEARCH STRATEGY: We searched the
      following databases for primary studies: Cochrane Central Register of Controlled
      Trials (CENTRAL) 2010, Issue 1, part of The Cochrane Library.
      www.thecochranelibrary.com, including the Cochrane Effective Practice and
      Organisation of Care (EPOC) Group Specialised Register (searched 8 July 2010);
      MEDLINE, Ovid (1948 to March Week 3 2011) (searched 30 March 2011); EMBASE, Ovid
      (1980 to 2010 Week 26) (searched 8 July 2010); CINAHL, EBSCO (1981 to present )
      (searched 8 July 2010); LILACS, VHL (1982 to present) (searched 8 July 2010);
      Sociological Abstracts, CSA Illumnia (1952 to current) (searched 8 July 2010).
      Reference lists of all papers and relevant reviews were identified and searched
      for additional studies. SELECTION CRITERIA: Included studies were randomized
      controlled trials (RCTs), non-randomized controlled trials (NRCTs), and
      interrupted-time-series (ITS) studies. Study participants were children aged 0 to
      4 years, caregivers, and health providers. Interventions included patient and
      community-oriented interventions, provider-oriented interventions, health system
      interventions, multi-faceted (any combination of the above categories of
      interventions), and any other single or multifaceted intervention intended to
      improve childhood immunisation coverage The primary outcome was the proportion of
      the target population fully immunized with recommended vaccines by age. DATA
      COLLECTION AND ANALYSIS: Two authors independently screened full articles of
      selected studies, extracted data, and assessed study quality. MAIN RESULTS: Six
      studies were included in the review; four were at high risk of bias. There was
      low quality evidence that: facility based health education may improve the uptake
      of combined vaccine against diphtheria, pertussis, and tetanus (DPT3) coverage
      (risk ratio (RR) 1.18; 95% CI 1.05 to 1.33); and also that a combination of
      facility based health education and redesigned immunization cards may improve
      DPT3 coverage (RR 1.36; 95% CI 1.22 to 1.51). There was also moderate quality
      evidence that: evidence-based discussions probably improve DPT3 coverage (RR
      2.17; 95% CI 1.80 to 2.61), and that information campaigns probably increase
      uptake of at least a dose of a vaccine (RR 1.43; 95% CI 1.01 to 2.02). AUTHORS'
      CONCLUSIONS: Home visits and health education may improve immunization coverage
      but the quality of evidence is low.

PMID- 21735424
TI  - Hepatic late adverse effects after antineoplastic treatment for childhood cancer.
AB  - BACKGROUND: Survival rates have greatly improved as a result of more effective
      treatments for childhood cancer. Unfortunately the improved prognosis has
      resulted in the occurrence of late, treatment-related complications. Liver
      complications are common during and soon after treatment for childhood cancer.
      However, among long-term childhood cancer survivors the risk of hepatic late
      adverse effects is largely unknown. To make informed decisions about future
      cancer treatment and follow-up policies it is important to know the risk of, and
      associated risk factors for, hepatic late adverse effects. OBJECTIVES: To
      evaluate the existing evidence on the association between antineoplastic
      treatment for childhood cancer and hepatic late adverse effects. SEARCH STRATEGY:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009) and EMBASE (1980 to
      June 2009). In addition, we searched reference lists of relevant articles and
      conference proceedings. SELECTION CRITERIA: All studies except case reports, case
      series and studies including less than 10 patients that examined the association
      between antineoplastic treatment for childhood cancer (aged 18 years or less at
      diagnosis) and hepatic late adverse effects (one year or more after the end of
      treatment). DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed the study selection, risk of bias assessment and data extraction. MAIN
      RESULTS: We identified 20 cohort studies investigating hepatic late adverse
      effects after antineoplastic treatment for childhood cancer. All studies had
      methodological limitations. The prevalence of hepatic late adverse effects varied
      widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late
      adverse effects was well defined as alanine aminotransferase (ALT) above the
      upper limit of normal resulted in five studies. In this subgroup the prevalence
      of hepatic late adverse effects ranged from 8.0% to 52.8%, with follow-up
      durations varying from one to 27 years after the end of treatment. A more
      stringent selection process using the outcome definition of ALT as above twice
      the upper limit of normal resulted in three studies, with a prevalence ranging
      from 7.9% to 44.8%. Chronic viral hepatitis was identified as a risk factor for
      hepatic late adverse effects in univariate analyses. It is unclear which specific
      antineoplastic treatments increase the risk of hepatic late adverse effects
      AUTHORS' CONCLUSIONS: The prevalence of hepatic late adverse effects ranged from
      7.9% to 52.8% when selecting studies with an adequate outcome definition. It has
      not been established which childhood cancer treatments result in hepatic late
      adverse effects. There is a suggestion that chronic viral hepatitis increases the
      risk of hepatic late adverse effects. More well-designed studies are needed to
      reliably evaluate the prevalence of, and risk factors for, hepatic late adverse
      effects after antineoplastic treatment for childhood cancer.

PMID- 21735425
TI  - Intranasal ipratropium bromide for the common cold.
AB  - BACKGROUND: The common cold is one of the most common illnesses in humans and
      constitutes an economic burden both in terms of productivity and expenditure for
      treatment. There is no proven cure for the common cold and symptomatic relief is
      the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has
      been addressed in several studies and might prove an effective treatment for the
      common cold. OBJECTIVES: To determine the effect of IB versus placebo or no
      treatment on severity of rhinorrhoea and nasal congestion in children and adults
      with the common cold. Subjective overall improvement was another primary outcome
      and side effects were reported as a secondary outcome. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue
      1) which contains the Acute Respiratory Infections Group's Specialised Register,
      MEDLINE (1950 to January week 4, 2011), MEDLINE in-process and other non-indexed
      citations (February 2011), EMBASE (1974 to February 2011), AMED (1985 to February
      2011), Biosis (1974 to February 2011) and LILACS (1985 to February 2011).
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IB to placebo
      or no treatment in children and adults with the common cold. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed trial
      quality. We used a standardised form to extract relevant data and we contacted
      trial authors for additional information. MAIN RESULTS: Seven trials with a total
      of 2144 participants were included. Four studies (1959 participants) addressed
      subjective change in severity of rhinorrhoea. All studies were consistent in
      reporting statistically significant changes in favour of IB. Nasal congestion was
      reported in four studies and was found to have no significant change between the
      two groups. Two studies found a positive response in the IB group for the global
      assessment of overall improvement. Side effects were more frequent in the IB
      group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly
      encountered side effects included nasal dryness, blood tinged mucus and
      epistaxis. AUTHORS' CONCLUSIONS: For people with the common cold, the existing
      evidence, which has some limitations, suggests that IB is likely to be effective
      in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was
      associated with more side effects compared to placebo or no treatment although
      these appeared to be well-tolerated and self-limiting. There is a need for
      larger, high-quality trials to determine the effectiveness of IB in relieving
      common cold symptoms.

PMID- 21735426
TI  - TPO receptor agonist for chronic idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: Chronic idiopathic thrombocytopenic purpura (ITP) is an acquired
      autoimmune disorder that is characterized predominantly by a low platelet count.
      Thrombopoietin (TPO) receptor agonists increase production of platelets by
      stimulating the TPO receptor in people with chronic ITP. OBJECTIVES: To determine
      the efficacy and safety of TPO receptor agonists in chronic ITP patients. SEARCH
      STRATEGY: We searched MEDLINE (from 1950 to March 2011), EMBASE (from 1974 to
      March 2011), and the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2011, Issue 3) to identify all randomized trials in chronic
      ITP. We also contacted authors of included studies and TPO receptor agonists
      manufacturers. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing
      TPO receptor agonists alone, or in combination with other drugs, to placebo, no
      treatment, other drugs, splenectomy or another TPO receptor agonist in patients
      with chronic ITP. DATA COLLECTION AND ANALYSIS: Two review authors independently
      screened papers, extracted data and assessed the risk of bias in the included
      studies. MAIN RESULTS: Six trials with 808 patients were included. Five studies
      compared TPO receptor agonists with placebo (romiplostim: 100, eltrombopag: 299,
      placebo: 175); one study compared TPO receptor agonists with standard of care
      (SOC) (romiplostim: 157; SOC: 77). SOC included a variety of therapies, such as
      glucocorticoid, anti-D immune globulin, intravenous immune globulin, rituximab,
      azathioprine, and so on. Overall survival, one of our primary outcomes, was not
      studied by these RCTs and we could not estimate number needed to treat (NNT).
      Another primary outcome, improving significant bleeding events, did not reveal
      any significant differences between the TPO receptor agonists group and the
      control group (placebo or SOC) (versus placebo risk ratio (RR) 0.48, 95%
      confidence interval (CI) 0.20 to 1.15; versus SOC RR 0.49, 95% CI 0.15 to
      1.63).For secondary outcomes, TPO receptor agonists statistically significantly
      improved overall platelet response (versus placebo RR 4.06, 95% CI 2.93 to 5.63;
      versus SOC RR 1.81, 95% CI 1.37 to 2.37), complete response (versus placebo RR
      9.29, 95% CI 2.32 to 37.15) and durable response (versus placebo RR 14.16, 95% CI
      2.91 to 69.01). There was a significant reduction in overall bleeding events (WHO
      grades 1 to 4) when compared to placebo (RR 0.78, 95% CI 0.68 to 0.89), but not
      when compared to SOC(RR 0.97, 95% CI 0.75 to 1.26).Total adverse events (Grades 1
      to 5) were not statistically significantly different between the treatment and
      control groups(both placebo and SOC) (versus placebo RR 1.04, 95% CI 0.95 to
      1.15; versus SOC RR 0.97, 95% CI 0.75 to 1.26). Total serious adverse events
      (Grade 3 and higher adverse events) were increased when patients receiving
      treatment with SOC (RR 0.61, 95% CI 0.40 to 0.92), but not receiving treatment
      with placebo (RR 0.92, 95% CI 0.61 to 1.38).There are selective and performance
      biases because of open-label and inadequate allocation. AUTHORS' CONCLUSIONS:
      There was currently no evidence to support that TPO receptor agonists are
      effective in chronic ITP. Compared to placebo or SOC, despite significantly
      increased platelet response, there was no evidence to demonstrate that TPO
      receptor agonists did improve significant bleeding events in chronic ITP. The
      effect on overall survival awaits further analysis. Although long-term studies
      are lacking, current data demonstrated adverse effects of TPO receptor agonists
      were similar to that of placebo and SOC.

PMID- 21735427
TI  - Chinese herbal medicines for hypercholesterolemia.
AB  - BACKGROUND: Hypercholesterolemia is an important key contributory factor for
      ischemic heart disease and is associated with age, high blood pressure, a family
      history of hypercholesterolemia, and diabetes. Chinese herbal medicines have been
      used for a long time as lipid-lowering agents. OBJECTIVES: To assess the effects
      of Chinese herbal medicines on hypercholesterolemia. SEARCH STRATEGY: We searched
      the following databases: The Cochrane Library (issue 8, 2010), MEDLINE (until
      July 2010), EMBASE (until July 2010 ), Chinese BioMedical Database (until July
      2010), Traditional Chinese Medical Literature Analysis and Retrieval System
      (until July 2010), China National Knowledge Infrastructure (until July 2010),
      Chinese VIP Information (until July 2010), Chinese Academic Conference Papers
      Database and Chinese Dissertation Database (until July 2010), and Allied and
      Complementary Medicine Database (until July 2010). SELECTION CRITERIA: We
      considered randomized controlled clinical trials in hypercholesterolemic
      participants comparing Chinese herbal medicines with placebo, no treatment, and
      pharmacological or non-pharmacological interventions. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed the risk
      of bias. We resolved any disagreements with this assessment through discussion
      and a decision was achieved based by consensus. We assessed trials for the risk
      of bias against key criteria: random sequence generation, allocation concealment,
      blinding of participants, incomplete outcome data, selective outcome reporting
      and other sources of bias. MAIN RESULTS: We included 22 randomized trials (2130
      participants). The mean treatment duration was 2.3 +/- 1.3 months (ranging from
      one to six months). Twenty trials were conducted in China and 18 trials were
      published in Chinese. Overall, the risk of bias of included trials was high or
      unclear. Five different herbal medicines were evaluated in the included trials,
      which compared herbs with conventional medicine in six comparisons (20 trials),
      or placebo (two trials). There were no outcome data in any of the trials on
      cardiovascular events and death from any cause. One trial each reported well
      being (no significant differences) and economic costs. No serious adverse events
      were observed. Xuezhikang was the most commonly used herbal formula investigated.
      A significant effect on total cholesterol (two trial, 254 participants) was shown
      in favor of Xuezhikang when compared with inositol nicotinate (mean difference
      (MD) -0.90 mmol/L, 95% confidence interval (CI) -1.13 to -0.68) . AUTHORS'
      CONCLUSIONS: Some herbal medicines may have cholesterol-lowering effects. Our
      findings have to be interpreted with caution due to high or unclear risk of bias
      of the included trials.

PMID- 21735428
TI  - Laryngeal mask airway surfactant administration for prevention of morbidity and
      mortality in preterm infants with or at risk of respiratory distress syndrome.
AB  - BACKGROUND: Laryngeal mask airway (LMA) administration is one way of delivering
      surfactant to the infant lung, with the potential benefit of avoiding
      endotracheal intubation and ventilation, ventilator induced lung injury and
      bronchopulmonary dysplasia (BPD). OBJECTIVES: To determine the effect of LMA
      surfactant administration either as prophylaxis or treatment compared to placebo,
      no treatment, or intratracheal surfactant administration on morbidity and
      mortality in preterm infants with, or at risk of, respiratory distress syndrome
      (RDS). SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, October 2010),
      MEDLINE and PREMEDLINE (1950 to October 2010), EMBASE (1980 to October 2010) and
      CINAHL (1982 to October 2010). We also searched proceedings of scientific
      meetings, clinical trial registries, Google Scholar and reference lists of
      identified studies, as well as contacting expert informants and surfactant
      manufacturers. SELECTION CRITERIA: Randomised, cluster-randomised or quasi
      randomised controlled trials of laryngeal mask surfactant administration compared
      to placebo, no treatment, or other routes of administration (nebulised,
      pharyngeal instillation of surfactant before the first breath, thin endotracheal
      catheter surfactant administration or intratracheal surfactant instillation) on
      morbidity and mortality in preterm infants at risk of RDS. We considered
      published, unpublished and ongoing trials. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed studies for eligibility and quality, and
      extracted data. MAIN RESULTS: We found no studies of prophylactic or early LMA
      surfactant administration. A single small study of late rescue LMA surfactant was
      identified as eligible for inclusion. The study enrolled 26 preterm infants born
      >= 1200 g with RDS on continuous positive airway pressure (nCPAP). LMA surfactant
      administration compared to no treatment resulted in a reduction in mean FiO(2)
      required to maintain oxygen saturation between 88% and 92% for 12 hours after the
      intervention. No significant difference was reported in subsequent mechanical
      ventilation and endotracheal surfactant, pneumothorax, days on intermittent
      positive airway pressure (IPPV), and days on IPPV or oxygen. AUTHORS'
      CONCLUSIONS: There is evidence from a single small trial that LMA surfactant
      administration in preterm infants >= 1200 g with established RDS may have a short
      term effect in reducing oxygen requirements although the study is underpowered to
      detect important clinical effects. Adequately powered trials are required to
      determine the effect of LMA surfactant administration for prevention or treatment
      of RDS in preterm infants. LMA surfactant administration should be limited to
      clinical trials.

PMID- 21735429
TI  - Interventions to manage dual practice among health workers.
AB  - BACKGROUND: Dual practice, whereby health workers hold two or more jobs, is a
      common phenomenon globally. In resource constrained low- and middle-income
      countries dual practice poses an ongoing threat to the efficiency, quality and
      equity of health services, especially in the public sector. Identifying effective
      interventions to manage dual practice is important. OBJECTIVES: To assess the
      effects of regulations implemented to manage dual practice. SEARCH STRATEGY:
      Databases searched included: The Cochrane Central Register of Controlled Trials
      (CENTRAL) 2011, Issue 4, part of The Cochrane Library.
      www.thecochranelibrary.com, including the Cochrane Effective Practice and
      Organisation of Care (EPOC) Group Specialised Register (searched 26 May 2011);
      MEDLINE In-Process & Other Non-Indexed Citations May 24, 2011 (searched 26 May
      2011); MEDLINE, Ovid (1948 to May week 2 2011) (searched 26 May 2011); EMBASE,
      Ovid (1980 to 2011 week 20) (searched 26 May 2011); Science Citation Index and
      Social Sciences Citation Index, ISI Web of Science (1975 to present) (searched 04
      December 2009); LILACS (searched January 2010); and AIM (December 2009) (searched
      18 December 2009). SELECTION CRITERIA: Randomized controlled trials, non
      randomized controlled trials, controlled before-and-after studies and interrupted
      time-series studies. Dual practice was defined as holding more than one job.
      Studies for inclusion were those focusing on interventions to manage dual
      practice among health professionals employed in the public health sector. DATA
      COLLECTION AND ANALYSIS: Two review authors independently applied the criteria
      for inclusion and exclusion of studies when scanning the identified titles and
      abstracts. The same two review authors independently screened full reports of
      selected citations. At each stage, results were compared and discrepancies
      settled through discussion. MAIN RESULTS: No studies were found which were
      eligible for inclusion in this review. AUTHORS' CONCLUSIONS: There is a need to
      rigorously evaluate the effects of interventions implemented to manage dual
      practice among health workers. However, there is still much that is unknown about
      dual practice itself. The designing of studies to evaluate the effects of
      interventions to manage dual practice could benefit from prior studies to assess
      the various manifestations of dual practice, their prevalence and their likely
      impacts on health services delivery. These findings would then inform the design
      of studies to evaluate interventions to manage dual practice.

PMID- 21735430
TI  - Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial
      dystrophy.
AB  - BACKGROUND: Fuchs endothelial dystrophy (FED), first described by Ernst Fuchsis
      in 1910, is a condition in which there is premature degeneration of corneal
      endothelial cells. When the number of endothelial cells is reduced to a
      significant degree fluid begins to accumulate within the cornea. As a result the
      cornea loses its transparency and the individual suffers a reduction in vision.
      The only successful surgical treatment for this condition is replacement of part
      or all of the cornea with healthy tissue from a cadaveric donor. The established
      procedure, penetrating keratoplasty (PKP), has been used for many years and its
      safety and efficacy are well known. Endothelial keratoplasty (EK) is a relatively
      new surgical procedure and the safety and efficacy relative to PKP are unknown.
      OBJECTIVES: The objective of this review is to collate information on the
      benefits and complications related to two surgical methods (PKP and EK) of
      replacing the diseased endothelial layer of the cornea with a healthy layer in
      people with FED. SEARCH STRATEGY: We searched CENTRAL (which contains the
      Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue
      2), MEDLINE (January 1950 to February 2011), EMBASE (January 1980 to February
      2011), Latin American and Caribbean Health Sciences Literature Database (LILACS)
      (January 1982 to February 2011), the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov).
      There were no date or language restrictions in the electronic searches for
      trials. The electronic databases were last searched on 6 February 2011. SELECTION
      CRITERIA: We included all randomised controlled trials (RCTs) comparing EK versus
      PKP for people (of any age and gender) who had been clinically diagnosed with
      FED. When assessing the primary and secondary outcome measures, only RCTs were
      included in the analysis. As per our protocol a description of data from non
      randomised comparative studies is also reported. As RCTs may not detect
      differences in frequency of adverse events, when assessing these we included data
      from cohort studies with more than 50 participants and a follow-up of up to five
      years. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial
      quality and extracted data. MAIN RESULTS: The electronic searches identified one
      RCT, five non-randomised comparative studies and 34 cohort studies with a sample
      size of over 50 participants for inclusion. The RCT was conducted in the USA and
      included 28 eyes of 25 participants with FED. Although this is a very good RCT,
      there may be potential for bias due to lack of masking of assessors and possible
      selective reporting not being clearly reported. In this RCT, comparing EK versus
      PKP, best corrected visual acuity (BCVA) was similar at 24 months (PKP 0.20 +/-
      0.20 logMAR; EK 0.34 +/- 0.35 logMAR; P = 0.23) and higher order aberrations
      (HOAs) (deviations of the performance of an optical system from the predictions
      of paraxial optics) were lower with EK. No other data were reported by the trial.
      Based on data obtained from both non-randomised comparative studies and
      individual cohort studies the endothelial rejection rate was between 5.3% and
      23.2% for PKP and 2% and 4% for EK. However the mean follow-up duration in the EK
      cohort studies was noticeably shorter. The rate of EK graft dislocation requiring
      repositioning ranged from 3% to 63%, with the majority of studies having a rate
      of < 10%. AUTHORS' CONCLUSIONS: There is no high quality evidence that EK is
      superior to PKP in the treatment of FED considering the studies that satisfied
      our primary and secondary outcome measures. One RCT demonstrated that HOAs are
      lower following EK and some lower quality evidence suggests that endothelial
      rejection episodes may be less with EK. These findings should be interpreted with
      caution as they are based on data with risk of biases. Further RCTs of visual and
      refractive outcomes needs to be performed in this field, comparing EK to PKP,
      with a larger sample size and at least five years of follow up. To avoid bias due
      to a surgeon's learning curve, procedures should be performed by experienced
      surgeons only. Quality of life and vision should also be evaluated. The risk of
      endothelial rejection will be difficult to address in the context of a RCT
      because of power considerations but large non-randomised comparative case series
      and corneal graft registry outcome data will be useful in this regard.

PMID- 21735431
TI  - Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax
      malaria.
AB  - BACKGROUND: Plasmodium vivax is an important cause of malaria in many parts of
      Asia and South America, and resistance to the standard treatment (chloroquine) is
      now high in some parts of Oceania. This review aims to assess the current
      treatment options in the light of rising chloroquine resistance. OBJECTIVES: To
      compare Artemisinin-based combination therapies (ACTs) with alternative
      antimalarial regimens for treating acute uncomplicated P.vivax malaria. SEARCH
      STRATEGY: We searched the Cochrane Infectious Disease Group Specialized Register;
      the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE;
      LILACS and the metaRegister of Controlled Trials (mRCT) using  "vivax" and "arte*
      OR dihydroarte*"  as search terms. SELECTION CRITERIA: Randomized controlled
      trials comparing ACTs versus standard therapy, or comparing alternative ACTs, in
      adults and children with uncomplicated P. vivax malaria. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trials for eligibility and risk of
      bias, and extracted data. Recurrent parasitaemia prior to day 28 was taken as a
      proxy for effective treatment of the blood stage parasite, and drugs compared
      using risk ratios (RR) and 95% confidence intervals (CI). Trials following
      patients for longer than 28 days were used to assess the duration of the post
      treatment prophylactic effect of ACTs. The quality of evidence has been assessed
      using the GRADE methodology. MAIN RESULTS: ACTs vs chloroquineIn settings where
      chloroquine remains effective, ACTs are equivalent at preventing recurrent
      parasitemias before day 28 (four trials, 1185 participants; RR 1, 95% CI 0.30 to
      3.39, high quality evidence).ACT combinations with long half-lives are probably
      superior to chloroquine over six to eight weeks follow-up, with significantly
      fewer recurrent episodes 0 after day 28 (two trials, 668 participants, RR 0.47,
      95% CI 0.29 to 0.76, moderate quality evidence). It is not clear if this effect
      is still present if primaquine is given.Dihydroartemisinin-piperaquine versus
      alternative ACTsDihydroartemisinin-piperaquine is the most studied ACT for the
      treatment of P. vivax. In high transmission settings it is probably superior to
      artemether-lumefantrine, artesunate plus sulphadoxine-pyrimethamine and
      artesunate plus amodiaquine at preventing recurrent parasitemias before day 28
      (three trials, 334 participants, RR 0.20, 95% CI 0.08 to 0.49, moderate quality
      evidence).This advantage with dihydroartemisinin-piperaquine may last for at
      least six weeks even when primaquine is also given to achieve radical cure; with
      fewer recurrent parasitemias occurring between day 28 and day 42 (two trials, 179
      participants, RR 0.21, 95% CI 0.10 to 0.46, low quality evidence).The data
      available from low transmission settings is too limited to make conclusions about
      the relative effectiveness of ACTs. AUTHORS' CONCLUSIONS: ACTs appear at least
      equivalent to chloroquine at effectively treating the blood stage P. vivax
      infection. Even where chloroquine remains effective this finding may allow for
      simplified protocols treating all forms of malaria with ACTs.Dihydroartemisinin
      piperaquine may provide a longer period of post-treatment prophylaxis than
      artemether-lumefantrine or artesunate plus amodiaquine, which is likely to be a
      function of the long elimination half-life of piperaquine. This effect may be
      clinically important in high transmission settings whether primaquine is also
      given or not.

PMID- 21735432
TI  - Intratympanic steroids for Meniere's disease or syndrome.
AB  - BACKGROUND: Meniere's disease is a disorder characterised by hearing loss,
      tinnitus and disabling vertigo. The use of intratympanic steroids to reduce the
      severity of these symptoms has been gaining popularity. OBJECTIVES: To assess the
      effectiveness of intratympanic steroids on the frequency and severity of attacks
      of vertigo, on chronic symptoms such as tinnitus, imbalance and hearing loss, and
      on the progression of these symptoms in patients with definite Meniere's disease
      or syndrome, as defined by the AAO-HNS Committee. SEARCH STRATEGY: We searched
      the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane
      Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of
      Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional
      sources for published and unpublished trials. The date of the most recent search
      was 13 January 2011. SELECTION CRITERIA: Randomised controlled trials of
      intratympanic dexamethasone versus placebo in patients with Meniere's disease.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial risk of
      bias and extracted data. We contacted study authors for further information where
      possible. MAIN RESULTS: A single trial containing 22 patients, with a low risk of
      bias was included. This trial found that after 24 months, compared with placebo,
      the use of intratympanic dexamethasone demonstrated a statistically significant
      improvement in vertigo as defined by a respective improvement in functional level
      (90% versus 42%), class (82% versus 57%), change in Dizziness Handicap Inventory
      scores (60.4 versus 41.3) and mean vertigo subjective improvement (90% versus
      57%). The treatment regime described by the authors involved daily injections of
      dexamethasone solution 4 mg/ml for five consecutive days. These results were
      clinically significant. No complications were reported. AUTHORS' CONCLUSIONS: The
      results of a single trial provide limited evidence to support the effectiveness
      of intratympanic steroids in patients with Meniere's disease. This trial
      demonstrated a statistically and clinically significant improvement of the
      frequency and severity of vertigo measured 24 months after the treatment was
      administered. It is important to note that there were a few aspects of the study
      which we were unable to clarify with the study authors.

PMID- 21735433
TI  - Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis.
AB  - BACKGROUND: Dilation of sinus ostia using a high-pressure balloon has been
      introduced as a treatment for chronic rhinosinusitis (CRS) refractory to medical
      treatment. The efficacy of this technology, however, has not been systematically
      reviewed. OBJECTIVES: To assess the effectiveness of balloon sinus ostial
      dilation as a treatment for patients suffering with CRS refractory to medical
      treatment. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat
      Disorders Group Trials Register; CENTRAL; PubMed; EMBASE; CINAHL; Web of Science;
      BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources
      for published and unpublished trials. The date of the most recent search was 20
      December 2010. SELECTION CRITERIA: Randomised controlled trials in patients of
      any age with rhinosinusitis lasting longer than 12 weeks who have failed a
      prolonged course of medical treatment. Studies compared either balloon sinus
      ostial dilation or a hybrid procedure (balloon dilation in conjunction with
      functional endoscopic sinus surgery (FESS)) versus conventional surgery (e.g.
      FESS) or a waiting list control. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected studies for inclusion, extracted data and assessed risk of
      bias. MAIN RESULTS: One study (34 patients) met our inclusion criteria although
      it was not yet a peer reviewed publication. The study randomised patients with
      chronic frontal sinusitis who had failed a prolonged course of medical treatment
      into two groups: balloon dilatation of the frontal recess (plus conventional FESS
      of other involved sinuses) versus conventional FESS (Draf type 1/2a procedures on
      the frontal sinuses). At 12 months follow up there was no statistically
      significant difference in radiological resolution of frontal sinuses between the
      two groups. The percentages of directly observed patent frontal recesses at 12
      months were 75% in the balloon dilation group versus 63% in the FESS-only group.
      The authors state that this was statistically significant but details of the
      analysis were not presented. Indeed the study as a whole suffers from a bias in
      the way its outcome measures were reported.No major complications were reported.
      Three patients in the FESS-only group required further revision frontal sinus
      surgery compared to one in the balloon dilation group, although synechiae were
      more common in the latter. AUTHORS' CONCLUSIONS: At present there is no
      convincing evidence supporting the use of endoscopic balloon sinus ostial
      dilation compared to conventional surgical modalities in the management of CRS
      refractory to medical treatment. With the escalating use of balloon sinuplasty,
      there is an urgent need for more randomised controlled trials to determine its
      efficacy over conventional surgical treatment modalities.

PMID- 21735434
TI  - Botulinum toxin for subacute/chronic neck pain.
AB  - BACKGROUND: Neck disorders are common, disabling and costly. Botulinum toxin
      (BoNT) intramuscular injections are often used with the intention of treating
      neck pain. OBJECTIVES: To systematically evaluate the literature on the treatment
      effectiveness of BoNT for neck pain, disability, global perceived effect and
      quality of life in adults with neck pain with or without associated cervicogenic
      headache, but excluding cervical radiculopathy and whiplash associated disorder.
      SEARCH STRATEGY: We searched CENTRAL, MEDLINE, AMED, Index to Chiropractic
      Literature, CINAHL, LILACS, and EMBASE from their origin to 20 September 2010.
      SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials
      in which BoNT injections were used to treat subacute or chronic neck pain. DATA
      COLLECTION AND ANALYSIS: A minimum of two review authors independently selected
      articles, abstracted data, and assessed risk of bias, using the Cochrane Back
      Review Group criteria. In the absence of clinical heterogeneity, we calculated
      standardized mean differences (SMD) and relative risks, and performed meta
      analyses using a random-effects model. The quality of the evidence and the
      strength of recommendations were assigned an overall grade for each outcome. MAIN
      RESULTS: We included nine trials (503 participants). Only BoNT type A (BoNT-A)
      was used in these studies.High quality evidence suggests there was little or no
      difference in pain between BoNT-A and saline injections at four weeks (five
      trials; 252 participants; SMD pooled -0.07 (95% confidence intervals (CI) -0.36
      to 0.21)) and six months for chronic neck pain. Very low quality evidence
      indicated little or no difference in pain between BoNT-A combined with
      physiotherapeutic exercise and analgesics and saline injection with
      physiotherapeutic exercise and analgesics for patients with chronic neck pain at
      four weeks (two trials; 95 participants; SMD pooled 0.09 (95% CI -0.55 to 0.73))
      and six months (one trial; 24 participants; SMD -0.56 (95% CI -1.39 to 0.27)).
      Very low quality evidence from one trial (32 participants) showed little or no
      difference between BoNT-A and placebo at four weeks (SMD 0.16 (95% CI -0.53 to
      0.86)) and six months (SMD 0.00 (95% CI -0.69 to 0.69)) for chronic cervicogenic
      headache. Very low quality evidence from one trial (31 participants), showed a
      difference in global perceived effect favouring BoNT-A in chronic neck pain at
      four weeks (SMD -1.12 (95% CI: -1.89 to -0.36)). AUTHORS' CONCLUSIONS: Current
      evidence fails to confirm either a clinically important or a statistically
      significant benefit of BoNT-A injection for chronic neck pain associated with or
      without associated cervicogenic headache. Likewise, there was no benefit seen for
      disability and quality of life at four week and six months.

PMID- 21735435
TI  - Immediate versus delayed reconstruction following surgery for breast cancer.
AB  - BACKGROUND: Breast cancer is the most prevalent cancer in women and has a
      lifetime incidence of one in nine in the UK. Curative treatment requires surgery,
      and may involve adjuvant and neo-adjuvant therapy. In many women, post-mastectomy
      breast reconstruction is essential to restore body image and improve quality of
      life. Timing of reconstruction may be immediately at the time of mastectomy or
      delayed until after surgery. Outcomes such as psychosocial morbidity, aesthetics
      and complications rates may differ between the two approaches. OBJECTIVES: To
      assess the effects of immediate versus delayed reconstruction following surgery
      for breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group
      (CBCG) Specialised Register on 22 July 2010, MEDLINE from July 2008 to 26 August
      2010, EMBASE from 2008 to 26 August 2010 and the WHO International Clinical
      Trials Registry Platform (ICTRP) on 26 August 2010. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing immediate breast reconstruction
      versus delayed or no reconstruction in women in any age group and stage of breast
      cancer. We considered any recognised methods of reconstruction to one or both
      breasts undertaken at the same time as mastectomy or at any time following
      mastectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently
      screened papers, extracted trial details and assessed the risk of bias in the one
      eligible study. MAIN RESULTS: We included only one RCT that involved that
      involved 64 women.We judged this study as being at a high risk of bias. Post
      operative morbidity and mortality were not addressed, and secondary outcomes of
      patient cosmetic evaluations and psychosocial well-being post-reconstruction were
      inadequately reported. Based on limited data there was some, albeit unreliable,
      evidence that immediate reconstruction compared with delayed or no
      reconstruction, reduced psychiatric morbidity reported three months post
      operatively. AUTHORS' CONCLUSIONS: The current level of evidence for the
      effectiveness of immediate versus delayed reconstruction following surgery for
      breast cancer was based on a single RCT with methodological flaws and a high risk
      of bias, which does not allow confident decision-making about choice between
      these surgical options. Until high quality evidence is available, clinicians may
      wish to consider the recommendations of relevant guidelines and protocols.
      Although the limitations and ethical constraints of conducting RCTs in this field
      are recognised, adequately powered controlled trials with a focus on clinical and
      psychological outcomes are still required. Given the paucity of RCTs in this
      subject, in future versions of this review we will look at study designs other
      than RCTs specifically good quality cohort and case-controlstudies.

PMID- 21735436
TI  - Low-dose rate brachytherapy for men with localized prostate cancer.
AB  - BACKGROUND: Localized prostate cancer is a slow growing tumor for many years for
      the majority of affected men. Low-dose rate brachytherapy (LDR-BT) is short
      distance radiotherapy using low-energy radioactive sources. LDR-BT has been
      recommended for men with low risk localized prostate cancer. OBJECTIVES: To
      assess the benefit and harm of LDR-BT compared to radical prostatectomy (RP),
      external beam radiotherapy (EBRT), and no primary therapy (NPT) in men with
      localized prostatic cancer. SEARCH STRATEGY: The Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE (from 1950), and EMBASE (from 1980) were
      searched in June 2010 as well as online trials registers and reference lists of
      reviews. SELECTION CRITERIA: Randomized, controlled trials comparing LDR-BT
      versus RP, EBRT, and NPT in men with clinically localized prostate cancer. DATA
      COLLECTION AND ANALYSIS: Data on study methods, participants, treatment regimens,
      observation period and outcomes were recorded by two reviewers independently.
      MAIN RESULTS: We identified only one RCT (N = 200; mean follow up 68 months).
      This trial compared LDR-BT and RP. The risk of bias was deemed high. Primary
      outcomes (overall survival, cause-specific mortality, or metastatic-free
      survival) were not reported. Biochemical recurrence-free survival at 5 years
      follow up was not significantly different between LDR-BT (78/85 (91.8%)) and RP
      (81/89 (91.0%)); P = 0.875; relative risk 0.92 (95% CI: 0.35 to 2.42).For severe
      adverse events reported at 6 months follow up, results favored LDR-BT for urinary
      incontinence (LDR-BT 0/85 (0.0%) versus RP 16/89 (18.0%); P < 0.001; relative
      risk 0) and favored RP for urinary irritation (LDR-BT 68/85 (80.0%) versus RP
      4/89 (4.5%); P < 0.001; relative risk 17.80, 95% CI 6.79 to 46.66). The
      occurrence of urinary stricture did not significantly differ between the
      treatment groups (LDR-BT 2/85 (2.4%) versus RP 6/89 (6.7%); P = 0.221; relative
      risk 0.35, 95% CI: 0.07 to 1.68). Long-term information was not available.We did
      not identify significant differences of mean scores between treatment groups for
      patient-reported outcomes function and bother as well as generic health-related
      quality of life. AUTHORS' CONCLUSIONS: Low-dose rate brachytherapy did not reduce
      biochemical recurrence-free survival versus radical prostatectomy at 5 years. For
      short-term severe adverse events, low-dose rate brachytherapy was significantly
      more favorable for urinary incontinence, but radical prostatectomy was
      significantly more favorable for urinary irritation. Evidence is based on one RCT
      with high risk of bias.

PMID- 21735437
TI  - Single incision versus conventional multi-incision appendicectomy for suspected
      appendicitis.
AB  - BACKGROUND: Appendicectomy is a well established surgical procedure used in the
      management of acute appendicitis.  The operation can be performed with minimally
      invasive surgery (laparoscopic) or as an open procedure. A recent development in
      appendicectomy has been the introduction of less invasive single incision
      laparoscopic surgery, using a single multi-luminal port or multiple mono-luminal
      ports, through a single skin incision. There are yet unanswered questions
      regarding the efficacy of this new and novel technique including: patient benefit
      and satisfaction, complications, long-term outcomes, and survival. OBJECTIVES:
      The aim of this review is to perform meta-analysis using data from available
      trials comparing single incision with conventional multi-incision laparoscopic
      appendicectomy for appendicitis, in order to ascertain any differences in
      outcome. SEARCH STRATEGY: We searched the electronic databases including
      MEDLINE/PubMed (from 1980 to December 2010), EMBASE/Ovid (from 1980 to December
      2010) and CENTRAL (The Cochrane Library 2010, Issue 11) with pre-specified terms.
      We also searched reference lists of relevant articles and reviews, conference
      proceedings and ongoing trial databases. SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials of patients with appendicitis, or symptoms of
      appendicitis, undergoing laparoscopic appendicectomy, in which at least one arm
      involves single incision procedures and another multi-incision procedures. DATA
      COLLECTION AND ANALYSIS: There were no RCTs or prospectively controlled trials
      found that met the inclusion criteria. MAIN RESULTS: Three authors performed
      study selection independently.No studies that met the inclusion criteria of this
      review were identified. Current evidence exists only the form of case-series.This
      review has been authored as 'empty' pending the results of 5 ongoing trials.
      AUTHORS' CONCLUSIONS: No RCTs comparing single incision laparoscopic appendectomy
      with multi-incision surgery could be identified. No definitive conclusions can be
      made at this time. Well designed prospective RCTs are required in order to
      evaluate benefit or harm from laparoscopic surgical approaches for
      appendicectomy. Until appropriate data has been reported, the institutional
      polices of healthcare providers must be based on the clinical judgement of
      experts in the field.

PMID- 21735438
TI  - Aromatherapy for pain management in labour.
AB  - BACKGROUND: Many women would like to avoid pharmacological or invasive methods of
      pain management in labour and this may contribute towards the popularity of
      complementary methods of pain management. This review examined currently
      available evidence supporting the use of aromatherapy for pain management in
      labour. OBJECTIVES: To examine the effects of aromatherapy for pain management in
      labour on maternal and perinatal morbidity. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2010), The
      Cochrane Complementary Medicine Field's Trials Register (October 2010), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue
      4), MEDLINE (1966 to 31 October 2010), CINAHL (1980 to 31 October 2010), the
      Australian and New Zealand Trials Registry (31 October 2010), Chinese Clinical
      Trial Register (31 October 2010), Current Controlled Trials (31 October 2010),
      ClinicalTrials.gov (31 October 2010), ISRCTN Register (31 October 2010), National
      Center for Complementary and Alternative Medicine (NCCAM) (31 October 2010) and
      the WHO International Clinical Trials Registry Platform (31 October 2010).
      SELECTION CRITERIA: Randomised controlled trials comparing aromatherapy with
      placebo, no treatment or other non-pharmacological forms of pain management in
      labour. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial
      quality and extracted data. We contacted study authors for additional
      information. MAIN RESULTS: We included two trials (535 women) in the review. The
      trials found no difference between groups for the primary outcomes of pain
      intensity, assisted vaginal birth (risk ratio (RR) 1.04, 95% confidence interval
      (CI) 0.48 to 2.28, one trial, 513 women; RR 0.83, 95% CI 0.06 to 11.70, one
      trial, 22 women), and caesarean section (RR 0.98, 95% CI 0.49 to 1.94, one trial,
      513 women; RR 2.54, 95% CI 0.11 to 56.25, one trial, 22 women); there were more
      babies admitted to neonatal intensive care in the control group of one trial (RR
      0.08, 95% CI 0.00 to 1.42, one trial, 513 women) but this difference did not
      reach statistical significance. The trials found no differences between groups
      for the secondary outcomes of use of pharmacological pain relief (RR 0.35, 95% CI
      0.04 to 3.32, one trial, 513 women; RR 2.50, 95% CI 0.31 to 20.45, one trial, 22
      women), spontaneous vaginal delivery (RR 1.00, 95% CI 0.94 to 1.06, one trial,
      513 women; RR 0.93, 95% CI 0.67 to 1.28, one trial, 22 women) or length of labour
      and augmentation (RR 1.14, 95% CI 0.90 to 1.45, one trial, 513 women). The risk
      of bias was low in the trials. AUTHORS' CONCLUSIONS: There is a lack of studies
      evaluating the role of aromatherapy for pain management in labour. Further
      research is needed before recommendations can be made for clinical practice.

PMID- 21735439
TI  - Reduced dietary salt for the prevention of cardiovascular disease.
AB  - BACKGROUND: An earlier Cochrane review of dietary advice identified insufficient
      evidence to assess effects of reduced salt intake on mortality or cardiovascular
      events. OBJECTIVES: 1. To assess the long term effects of interventions aimed at
      reducing dietary salt on mortality and cardiovascular morbidity.2. To investigate
      whether blood pressure reduction is an explanatory factor in any effect of such
      dietary interventions on mortality and cardiovascular outcomes. SEARCH STRATEGY:
      The Cochrane Library (CENTRAL, Health Technology Assessment (HTA) and Database of
      Abstracts of Reviews of Effect (DARE)), MEDLINE, EMBASE, CINAHL and PsycInfo were
      searched through to October 2008. References of included studies and reviews were
      also checked. No language restrictions were applied. SELECTION CRITERIA: Trials
      fulfilled the following criteria: (1) randomised with follow up of at least six
      months, (2) intervention was reduced dietary salt (restricted salt dietary
      intervention or advice to reduce salt intake), (3) adults, (4) mortality or
      cardiovascular morbidity data was available. Two reviewers independently assessed
      whether studies met these criteria. DATA COLLECTION AND ANALYSIS: Data extraction
      and study validity were compiled by a single reviewer, and checked by a second.
      Authors were contacted where possible to obtain missing information. Events were
      extracted and relative risks (RRs) and 95% CIs calculated. MAIN RESULTS: Seven
      studies (including 6,489 participants) met the inclusion criteria - three in
      normotensives (n=3518), two in hypertensives (n=758), one in a mixed population
      of normo- and hypertensives (n=1981) and one in heart failure (n=232) with end of
      trial follow-up of seven to 36 months and longest observational follow up (after
      trial end) to 12.7 yrs. Relative risks for all cause mortality in normotensives
      (end of trial RR 0.67, 95% CI: 0.40 to 1.12, 60 deaths; longest follow up RR
      0.90, 95% CI: 0.58 to 1.40, 79 deaths) and hypertensives (end of trial RR 0.97,
      95% CI: 0.83 to 1.13, 513 deaths; longest follow up RR 0.96, 95% CI; 0.83 to
      1.11, 565 deaths) showed no strong evidence of any effect of salt reduction.
      Cardiovascular morbidity in people with normal blood pressure (longest follow-up
      RR 0.71, 95% CI: 0.42 to 1.20, 200 events) or raised blood pressure at baseline
      (end of trial RR 0.84, 95% CI: 0.57 to 1.23, 93 events) also showed no strong
      evidence of benefit. Salt restriction increased the risk of all-cause death in
      those with congestive heart failure (end of trial relative risk: 2.59, 95% 1.04
      to 6.44, 21 deaths). We found no information on participants health-related
      quality of life. AUTHORS' CONCLUSIONS: Despite collating more event data than
      previous systematic reviews of randomised controlled trials (665 deaths in some
      6,250 participants), there is still insufficient power to exclude clinically
      important effects of reduced dietary salt on mortality or cardiovascular
      morbidity in normotensive or hypertensive populations. Further RCT evidence is
      needed to confirm whether restriction of sodium is harmful for people with heart
      failure. Our estimates of benefits from dietary salt restriction are consistent
      with the predicted small effects on clinical events attributable to the small
      blood pressure reduction achieved.

PMID- 21735440
TI  - Hospital at home: home-based end of life care.
AB  - BACKGROUND: The policy in a number of countries is to provide people with a
      terminal illness the choice of dying at home. This policy is supported by surveys
      indicating that the general public and patients with a terminal illness would
      prefer to receive end of life care at home. OBJECTIVES: To determine if providing
      home-based end of life care reduces the likelihood of dying in hospital and what
      effect this has on patients' symptoms, quality of life, health service costs and
      care givers compared with inpatient hospital or hospice care. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library) to October 2009, Ovid MEDLINE(R) 1950 to March 2011, EMBASE
      1980 to October 2009, CINAHL 1982 to October 2009 and EconLit to October 2009. We
      checked the reference lists of articles identified for potentially relevant
      articles. SELECTION CRITERIA: Randomised controlled trials, interrupted time
      series or controlled before and after studies evaluating the effectiveness of
      home-based end of life care with inpatient hospital or hospice care for people
      aged 18 years and older. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted data and assessed study quality. We combined the published data for
      dichotomous outcomes using fixed-effect Mantel-Haenszel meta-analysis. When
      combining outcome data was not possible we presented the data in narrative
      summary tables. MAIN RESULTS: We included four trials in this review. Those
      receiving home-based end of life care were statistically significantly more
      likely to die at home compared with those receiving usual care (RR 1.33, 95% CI
      1.14 to 1.55, P = 0.0002; Chi (2) = 1.72, df = 2, P = 0.42, I(2) = 0% (three
      trials; N=652)). We detected no statistically significant differences for
      functional status (measured by the Barthel Index), psychological well-being or
      cognitive status, between patients receiving home-based end of life care compared
      with those receiving standard care (which included inpatient care). Admission to
      hospital while receiving home-based end of life care varied between trials and
      this was reflected by high levels of statistically significant heterogeneity in
      this analysis. There was some evidence of increased patient satisfaction with
      home-based end of life care, and little evidence of the impact this form of care
      has on care givers. AUTHORS' CONCLUSIONS: The evidence included in this review
      supports the use of end of life home-care programmes for increasing the number of
      patients who will die at home, although the numbers of patients being admitted to
      hospital while receiving end of life care should be monitored. Future research
      should also systematically assess the impact of end of life home care on care
      givers.

PMID- 21735441
TI  - Acupuncture or acupressure for pain management in labour.
AB  - BACKGROUND: Many women would like to avoid pharmacological or invasive methods of
      pain management in labour and this may contribute towards the popularity of
      complementary methods of pain management. This review examined evidence
      supporting the use of acupuncture and acupressure for pain management in labour.
      OBJECTIVES: To examine the effects of acupuncture and acupressure for pain
      management in labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register and The Cochrane Complementary Medicine
      Field's Trials Register (October 2010), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to October
      2010), and CINAHL (1980 to October 2010). SELECTION CRITERIA: Published and
      unpublished randomised controlled trials comparing acupuncture and acupressure
      with placebo, no treatment or other non-pharmacological forms of pain management
      in labour. We included all women whether primiparous or multiparous, and in
      spontaneous or induced labour. DATA COLLECTION AND ANALYSIS: We performed meta
      analysis using risk ratios (RR) for dichotomous outcomes and mean differences
      (MD) for continuous outcomes. The outcome measures included pain intensity,
      satisfaction with pain relief, use of pharmacological pain relief, relaxation,
      caesarean section rate, augmentation with oxytocin, length of labour and anxiety.
      MAIN RESULTS: We included 13 trials with data reporting on 1986 women. Nine
      trials reported on acupuncture and four trials reported on acupressure. Less
      intense pain was found from acupuncture compared with no intervention
      (standardised mean difference (SMD) -1.00, 95% confidence interval (CI) -1.33 to 
      0.67, one trial, 163 women). One trial increased satisfaction with pain relief
      compared with placebo control (RR 2.38, 95% CI 1.78 to 3.19, 150 women). Reduced
      use of pharmacological analgesia was found in one trial of acupuncture compared
      with placebo (RR 0.72, 95% CI 0.58 to 0.88, 136 women), and compared with
      standard care, however, there was significant heterogeneity (RR 0.68, 95% CI 0.56
      to 0.83, three trials, 704 women). Fewer instrumental deliveries from acupuncture
      were found compared with standard care (RR 0.67, 95% CI 0.46, 0.98, three trials,
      704 women); however, there was significant heterogeneity. Pain intensity was
      reduced in the acupressure group compared with a placebo control (SMD -0.55, 95%
      CI -0.92 to -0.19, one trial, 120 women), and a combined control (SMD -0.42, 95%
      CI -0.65 to -0.18, two trials, 322 women). No trial was assessed as being at a
      low risk of bias for all of the quality domains. AUTHORS' CONCLUSIONS:
      Acupuncture and acupressure may have a role with reducing pain, increasing
      satisfaction with pain management and reduced use of pharmacological management.
      However, there is a need for further research.

PMID- 21735442
TI  - Feedback or biofeedback to augment pelvic floor muscle training for urinary
      incontinence in women.
AB  - BACKGROUND: Pelvic floor muscle training (PFMT) is an effective treatment for
      stress urinary incontinence in women. Whilst most of the PFMT trials have been
      done in women with stress urinary incontinence, there is also some trial evidence
      that PFMT is effective for urgency urinary incontinence and mixed urinary
      incontinence. Feedback or biofeedback are common adjuncts used along with PFMT to
      help teach a voluntary pelvic floor muscle contraction or to improve training
      performance. OBJECTIVES: To determine whether feedback or biofeedback adds
      further benefit to PFMT for women with urinary incontinence.To compare the
      effectiveness of different forms of feedback or biofeedback. SEARCH STRATEGY: We
      searched the Cochrane Incontinence Group Specialised Trials Register (searched 13
      May 2010) and the reference lists of relevant articles. SELECTION CRITERIA:
      Randomised or quasi-randomised trials in women with stress, urgency or mixed
      urinary incontinence (based on symptoms, signs or urodynamics). At least two arms
      of the trials included PFMT. In addition, at least one arm included verbal
      feedback or device-mediated biofeedback. DATA COLLECTION AND ANALYSIS: Trials
      were independently assessed for eligibility and risk of bias. Data were extracted
      by two reviewers and cross-checked. Disagreements were resolved by discussion or
      the opinion of a third reviewer. Data analysis was conducted in accordance with
      the Cochrane Handbook for Systematic Reviews of Intervention (version 5.1.0).
      Analysis within subgroups was based on whether there was a difference in PFMT
      between the two arms that had been compared. MAIN RESULTS: Twenty four trials
      involving 1583 women met the inclusion criteria; 17 trials contributed data to
      analysis for one of the primary outcomes. All trials contributed data to one or
      more of the secondary outcomes. Women who received biofeedback were significantly
      more likely to report that their urinary incontinence was cured or improved
      compared to those who received PFMT alone (risk ratio 0.75 , 95% confidence
      interval 0.66 to 0.86). However, it was common for women in the biofeedback arms
      to have more contact with the health professional than those in the non
      biofeedback arms. Many trials were at moderate to high risk of bias, based on
      trial reports. There was much variety in the regimens proposed for adding
      feedback or biofeedback to PFMT alone, and it was often not clear what the actual
      intervention comprised or what the purpose of the intervention was. AUTHORS'
      CONCLUSIONS: Feedback or biofeedback may provide benefit in addition to pelvic
      floor muscle training in women with urinary incontinence. However, further
      research is needed to differentiate whether it is the feedback or biofeedback
      that causes the beneficial effect or some other difference between the trial arms
      (such as more contact with health professionals).

PMID- 21735443
TI  - An overview of reviews evaluating the effectiveness of financial incentives in
      changing healthcare professional behaviours and patient outcomes.
AB  - BACKGROUND: There is considerable interest in the effectiveness of financial
      incentives in the delivery of health care. Incentives may be used in an attempt
      to increase the use of evidence-based treatments among healthcare professionals
      or to stimulate health professionals to change their clinical behaviour with
      respect to preventive, diagnostic and treatment decisions, or both. Financial
      incentives are an extrinsic source of motivation and exist when an individual can
      expect a monetary transfer which is made conditional on acting in a particular
      way. Since there are numerous reviews performed within the healthcare area
      describing the effects of various types of financial incentives, it is important
      to summarise the effectiveness of these in an overview to discern which are most
      effective in changing health professionals' behaviour and patient outcomes.
      OBJECTIVES: To conduct an overview of systematic reviews that evaluates the
      impact of financial incentives on healthcare professional behaviour and patient
      outcomes. METHODS: We searched the Cochrane Database of Systematic Reviews (CDSR)
      (The Cochrane Library); Database of Abstracts of Reviews of Effectiveness (DARE);
      TRIP; MEDLINE; EMBASE; Science Citation Index; Social Science Citation Index; NHS
      EED; HEED; EconLit; and Program in Policy Decision-Making (PPd) (from their
      inception dates up to January 2010). We searched the reference lists of all
      included reviews and carried out a citation search of those papers which cited
      studies included in the review. We included both Cochrane and non-Cochrane
      reviews of randomised controlled trials (RCTs), controlled clinical trials
      (CCTs), interrupted time series (ITSs) and controlled before and after studies
      (CBAs) that evaluated the effects of financial incentives on professional
      practice and patient outcomes, and that reported numerical results of the
      included individual studies. Two review authors independently extracted data and
      assessed the methodological quality of each review according to the AMSTAR
      criteria. We included systematic reviews of studies evaluating the effectiveness
      of any type of financial incentive. We grouped financial incentives into five
      groups: payment for working for a specified time period; payment for each
      service, episode or visit; payment for providing care for a patient or specific
      population; payment for providing a pre-specified level or providing a change in
      activity or quality of care; and mixed or other systems. We summarised data using
      vote counting. MAIN RESULTS: We identified four reviews reporting on 32 studies.
      Two reviews scored 7 on the AMSTAR criteria (moderate, score 5 to 7, quality) and
      two scored 9 (high, score 8 to 11, quality). The reported quality of the included
      studies was, by a variety of methods, low to moderate. Payment for working for a
      specified time period was generally ineffective, improving 3/11 outcomes from one
      study reported in one review. Payment for each service, episode or visit was
      generally effective, improving 7/10 outcomes from five studies reported in three
      reviews; payment for providing care for a patient or specific population was
      generally effective, improving 48/69 outcomes from 13 studies reported in two
      reviews; payment for providing a pre-specified level or providing a change in
      activity or quality of care was generally effective, improving 17/20 reported
      outcomes from 10 studies reported in two reviews; and mixed and other systems
      were of mixed effectiveness, improving 20/31 reported outcomes from seven studies
      reported in three reviews. When looking at the effect of financial incentives
      overall across categories of outcomes, they were of mixed effectiveness on
      consultation or visit rates (improving 10/17 outcomes from three studies in two
      reviews); generally effective in improving processes of care (improving 41/57
      outcomes from 19 studies in three reviews); generally effective in improving
      referrals and admissions (improving 11/16 outcomes from 11 studies in four
      reviews); generally ineffective in improving compliance with guidelines outcomes
      (improving 5/17 outcomes from five studies in two reviews); and generally
      effective in improving prescribing costs outcomes (improving 28/34 outcomes from
      10 studies in one review). AUTHORS' CONCLUSIONS: Financial incentives may be
      effective in changing healthcare professional practice. The evidence has serious
      methodological limitations and is also very limited in its completeness and
      generalisability. We found no evidence from reviews that examined the effect of
      financial incentives on patient outcomes.

PMID- 21735444
TI  - PIK3CA mutation is an early event in the development of endometriosis-associated
      ovarian clear cell adenocarcinoma.
AB  - Clear cell adenocarcinoma (CCA), a highly lethal histological subtype of ovarian
      carcinoma, is a type of human cancer with a high frequency of activating
      mutations in the PIK3CA gene. In this study, we aimed to determine how these
      mutations contribute to tumour development of CCAs. Exons 9 and 20 of the PIK3CA
      gene were analysed by direct genomic DNA sequencing of 23 CCAs with synchronous
      putative precursor lesions (ie endometriosis adjacent to carcinoma, with or
      without cytological atypia) and their mutational statuses were compared. Somatic
      mutations of the PIK3CA gene were detected in 10/23 (43%) carcinomas and in all
      cases the type of mutation was H1047R in the kinase domain. The identical H1047R
      mutation was also detected in the coexisting endometriotic epithelium, adjacent
      to the CCAs, in nine of ten (90%) cases. Moreover, in six of the nine lesions,
      the H1047R mutation was identified even in the endometrioses lacking cytological
      atypia. These findings provide evidence that mutations of the PIK3CA gene occur
      in the putative precursor lesions of CCA, strongly suggesting that they are very
      early events in tumourigenesis, probably initiating the malignant transformation
      of endometriosis. A specific kinase inhibitor to mutated PIK3CA may potentially
      be an effective therapeutic reagent against these carcinomas.

PMID- 21735445
TI  - Fattening by deprivation: methyl balance and perinatal cardiomyopathy.
AB  - Folate deficiency during pregnancy is associated with reduced birth weight, and a
      low birth weight is associated with increased cardiometabolic risk in adulthood.
      In the study by Moreno Garcia, Gueant-Rodriguez and colleagues reported in the
      current issue of the Journal of Pathology, the effect of methyl group deprivation
      in pregnancy on the neonatal myocardium was investigated. By utilizing a diet
      deficient in folate, vitamin B(12) and choline, the authors created a significant
      deficit of methyl groups in the fetus. During the weaning period and the
      concomitant shift from the relative hypoxia and glucose dependence of the
      gestational period to the aerobic, milk-derived high-fat metabolic environment of
      the weaning phase, the offspring developed a myocardial hypertrophy associated
      with disordered fatty acid oxidation and mitochondrial dysfunction. The
      functionality of PGC-1alpha, a master regulator of metabolic pathways including
      mitochondrial energetics and fatty acid oxidation, was found to be reduced in the
      methyl-deprived group, due to an imbalance in the ratio of methylation to
      acetylation. This study demonstrates that maternal methyl deprivation could
      'prime' the fetus by reducing its ability to oxidize fatty acids in the
      myocardium, thereby causing lipid accumulation and myocardial hypertrophy during
      exposure to high-fat diet in the weaning phase. This study has important
      implications for clinical perinatal cardiomyopathy and for the effect of maternal
      methyl group deprivation on the future risk of cardiovascular disease, and also
      potentially in enhancing the understanding of the elusive link between
      hyperhomocysteinaemic states in the adult and cardiovascular disease.

PMID- 21735446
TI  - Post-therapy pathologic stage and survival in patients with pancreatic ductal
      adenocarcinoma treated with neoadjuvant chemoradiation.
AB  - BACKGROUND: Neoadjuvant chemoradiation before surgery is an emerging treatment
      modality for pancreatic ductal adenocarcinoma (PDAC). However, analysis of
      prognostic factors is limited for patients with PDAC treated with neoadjuvant
      chemoradiation and pancreaticoduodenectomy (PD). METHODS: The study population
      was comprised of 240 consecutive patients with PDAC who received neoadjuvant
      chemoradiation and PD and was compared with 60 patients who had no neoadjuvant
      therapy between 1999 and 2007. Clinicopathologic features were correlated with
      disease-free survival (DFS) and overall survival (OS). RESULTS: Among the 240
      treated patients, the 1-year and 3-year DFS rates were 52% and 32%, with a median
      DFS of 15.1 months. The 1-year and 3-year OS rates were 95% and 47%, with a
      median OS of 33.5 months. By univariate analysis, DFS was associated with age,
      post-therapy tumor stage (ypT), lymph node status (ypN), number of positive lymph
      nodes, and American Joint Committee on Cancer (AJCC) stage, whereas OS was
      associated with intraoperative blood loss, margin status, ypT, ypN, number of
      positive lymph nodes, and AJCC stage. By multivariate analysis, DFS was
      independently associated with age, number of positive lymph nodes, and AJCC
      stage, and OS was independently associated with differentiation, margin status,
      number of positive lymph nodes, and AJCC stage. In addition, the treated patients
      had better OS and lower frequency of lymph node metastasis than those who had no
      neoadjuvant therapy. CONCLUSIONS: In patients with PDAC who received neoadjuvant
      chemoradiation and subsequent PD, post-therapy pathologic AJCC stage and number
      of positive lymph nodes are independent prognostic factors.

PMID- 21735447
TI  - Functional characterization of EMSY gene amplification in human cancers.
AB  - The 11q13-q14 locus is frequently amplified in human cancers, with a complex
      structure harbouring multiple potential oncogenic drivers. The EMSY gene has been
      proposed as a driver of the third core of the 11q13-q14 amplicon. This gene
      encodes a protein reported to be a BRCA2-binding partner, which when over
      expressed would lead to impairment of BRCA2 functions and could constitute a
      mechanism for BRCA2 inactivation in non-hereditary breast and ovarian cancers. We
      hypothesized that if EMSY amplification abrogates BRCA2 functions, cells
      harbouring this aberration would be unable to elicit competent homologous
      recombination DNA repair and, therefore, may have increased sensitivity to
      genotoxic therapies and potent PARP inhibitors. Microarray-based comparative
      genomic hybridization of cell lines from distinct tumour sites, including breast,
      ovary, pancreas, oesophagus, lung and the oral cavity, led to the identification
      of 10 cell lines with EMSY amplification and 18 without. EMSY amplification was
      shown to correlate with EMSY mRNA levels, although not all cell lines harbouring
      EMSY amplification displayed EMSY mRNA or protein over-expression. RNA
      interference-mediated silencing of EMSY did not lead to a reduction in cell
      viability in tumour models harbouring EMSY amplification. Cell lines with and
      without EMSY amplification displayed a similar ability to elicit RAD51 foci in
      response to DNA damaging agents, and similar sensitivity to cisplatin and
      olaparib. Taken together, this suggests that EMSY is unlikely to be a driver of
      the 11q13-q14 amplicon and does not have a dominant role in modulating the
      response to agents targeting cells with defective homologous recombination.

PMID- 21735448
TI  - L-Theanine: properties, synthesis and isolation from tea.
AB  - Theanine is a non-protein amino acid that occurs naturally in the tea plant
      (Camellia sinensis) and contributes to the favourable taste of tea. It is also
      associated with effects such as the enhancement of relaxation and the improvement
      of concentration and learning ability. It is also linked with health benefits
      including the prevention of certain cancers and cardiovascular disease, the
      promotion of weight loss and enhanced performance of the immune system. Thus,
      there has been a significant rise in the demand for theanine. While theanine has
      been chemically and biologically synthesised, techniques to isolate theanine from
      natural sources remain an important area of research. In this review article, the
      properties and health benefits of theanine are summarised and the synthesis and
      isolation of theanine are reviewed and discussed. Future perspectives for the
      isolation of theanine from natural sources are also outlined.

PMID- 21735449
TI  - Is the spin-orbit coupling important in the prediction of the 51V hyperfine
      coupling constants of V(IV) O2+ species? ORCA versus Gaussian performance and
      biological applications.
AB  - Density functional theory calculations of the (51)V hyperfine coupling (HFC)
      tensor A, have been completed for eighteen V(IV)O(2+) complexes with different
      donor set, electric charge and coordination geometry. A tensor was calculated
      with ORCA software with several functionals and basis sets taking into account
      the spin-orbit coupling contribution. The results were compared with those
      obtained with Gaussian 03 software using the half-and-half functional BHandHLYP
      and 6-311g(d,p) basis set. The order of accuracy of the functionals in the
      prediction of A(iso), A(z) and dipolar term A(z,anis) is BHandHLYP > PBE0 >> B3PW
      > TPSSh >> B3LYP >> BP86 > VWN5 (for A(iso)), BHandHLYP > PBE0 >> B3PW > TPSSh >
      B3LYP >> BP86 > VWN5 (for A(z)), B3LYP > PBE0 ~ B3PW ~ BHandHLYP >> TPSSh > BP86
      ~ VWN5 (for A(z,anis)). The good agreement in the prediction of A(z) with
      BHandHLYP is due to a compensation between the overestimation of A(iso) and
      underestimation of A(z,anis) (A(z) = A(iso) + A(z,anis)), whereas among the
      hybrid functionals PBE0 performs better than the other ones. BHandHLYP functional
      and Gaussian software are recommended when the V(IV)O(2+) species contains only V
      O and/or V-N bonds, whereas PBE0 functional and ORCA software for V(IV)O(2+)
      complexes with one or more V-S bonds. Finally, the application of these methods
      to the coordination environment of V(IV)O(2+) ion in V-proteins, like vanadyl
      substituted insulin, carbonic anhydrase, collagen and S-adenosylmethionine
      synthetase, was discussed.

PMID- 21735450
TI  - Toward a computational tool predicting the stereochemical outcome of asymmetric
      reactions: development of the molecular mechanics-based program ACE and
      application to asymmetric epoxidation reactions.
AB  - The development and application of ACE, a program that predicts the
      stereochemical outcome of asymmetric reactions is presented. As major
      implementations, ACE includes a genetic algorithm to carry out an efficient
      global conformational search combined with a conjugate gradient minimization
      routine for local optimization and a corner flap algorithm to search ring
      conformations. Further improvements have been made that enable ACE to generate
      Boltzmann populations of conformations, to investigate highly asynchronous
      reactions, to compute fluctuating partial atomic charges and solvation energy and
      to automatically construct reactants and products from libraries of catalysts and
      substrates. Validation on previously investigated reactions (asymmetric Diels
      Alder cycloadditions and organocatalyzed aldol reactions) followed by application
      to a number of alkene epoxidation reactions and a comparative study of DFT
      derived and ACE-derived predictions demonstrate the accuracy and usefulness of
      ACE in the context of asymmetric catalyst design.

PMID- 21735451
TI  - Counterpoise correction is not useful for short and Van der Waals distances but
      may be useful at long range.
AB  - This article investigates the errors in supermolecule calculations for the helium
      dimer. In a full CI calculation, there are two errors. One is the basis set
      superposition error (BSSE), the other is the basis set convergence error (BSCE).
      Both of the errors arise from the incompleteness of the basis set. These two
      errors make opposite contributions to the interaction energies. The BSCE is by
      far the largest error in the short range and larger than (but much closer to)
      BSSE around the Van der Waals minimum. Only at the long range, the BSSE becomes
      the larger error. The BSCE and BSSE largely cancel each other over the Van der
      Waals well. Accordingly, it may be recommended to not include the BSSE for the
      calculation of the potential energy curve from short distance till well beyond
      the Van der Waals minimum, but it may be recommended to include the BSSE
      correction if an accurate tail behavior is required. Only if the calculation has
      used a very large basis set, one can refrain from including the counterpoise
      correction in the full potential range. These results are based on full CI
      calculations with the aug-cc-pVXZ (X = D, T, Q, 5) basis sets.

PMID- 21735452
TI  - Surveying implicit solvent models for estimating small molecule absolute
      hydration free energies.
AB  - Implicit solvent models are powerful tools in accounting for the aqueous
      environment at a fraction of the computational expense of explicit solvent
      representations. Here, we compare the ability of common implicit solvent models
      (TC, OBC, OBC2, GBMV, GBMV2, GBSW, GBSW/MS, GBSW/MS2 and FACTS) to reproduce
      experimental absolute hydration free energies for a series of 499 small neutral
      molecules that are modeled using AMBER/GAFF parameters and AM1-BCC charges. Given
      optimized surface tension coefficients for scaling the surface area term in the
      nonpolar contribution, most implicit solvent models demonstrate reasonable
      agreement with extensive explicit solvent simulations (average difference 1.0-1.7
      kcal/mol and R(2)=0.81-0.91) and with experimental hydration free energies
      (average unsigned errors=1.1-1.4 kcal/mol and R(2)=0.66-0.81). Chemical classes
      of compounds are identified that need further optimization of their ligand force
      field parameters and others that require improvement in the physical parameters
      of the implicit solvent models themselves. More sophisticated nonpolar models are
      also likely necessary to more effectively represent the underlying physics of
      solvation and take the quality of hydration free energies estimated from implicit
      solvent models to the next level.

PMID- 21735453
TI  - Involvement of Th2 cytokines in the mouse model of flutamide-induced acute liver
      injury.
AB  - Drug-induced liver injury is a growing concern for pharmaceutical companies and
      patients because numerous drugs have been linked to hepatotoxicity and it is the
      most common reason for a drug to be withdrawn. Flutamide rarely causes liver
      dysfunction in humans, and immune allergic reactions have been suggested in some
      cases. In this study, we investigated the mechanisms of flutamide-induced liver
      injury in BALB/c mice. Plasma alanine aminotransferase and aspartate
      aminotransferase levels were significantly increased 3, 6 and 9 h after flutamide
      (1500 mg kg-1 , p.o.) administration. The biomarker for oxidative stress was not
      changed, but Th2-dominant immune-related factors, such as interleukin (IL)-4, IL
      5, STAT6 and GATA-binding protein (GATA)-3, were induced in flutamide
      administered mice. The pre-administration of monoclonal-IL-4 antibody suppressed
      the hepatotoxicity of flutamide. In addition, we investigated the effect of 13,14
      dihydro-15-keto-PGD2 (DK-PGD2; 10 ug per mouse, i.p.) administration on flutamide
      induced acute liver injury. Coadministration of DK-PGD2 and flutamide resulted in
      a significant increase in alanine aminotransferase and a remarkable increase of
      macrophage inflammatory protein-2. In conclusion, we demonstrated that flutamide
      induced acute liver injury is mediated by Th2-dominant immune responses in mice.

PMID- 21735454
TI  - An alkaline comet assay study on the antimalarial drug atovaquone in human
      peripheral blood lymphocytes: a study based on clinically relevant
      concentrations.
AB  - Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively
      targeting the mitochondrial respiratory chain of malaria parasite. It is used for
      both the treatment and prevention of malaria, usually in a fixed combination with
      proguanil. Although atovaquone has not often been associated with severe adverse
      reactions in the recommended dosages and has a relatively favorable side effect
      profile, the present study was undertaken to evaluate its cytogenotoxic potential
      towards human peripheral blood lymphocytes. Two different concentrations of
      atovaquone found in plasma when used in fixed-dose combination with proguanile
      hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1)
      used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of
      malaria. The results showed that lymphocyte viability was not affected after the
      treatment, suggesting that atovaquone was not cytotoxic in the given
      concentrations. With the alkaline comet assay we demonstrated that in human
      peripheral blood lymphocytes no significant changes in comet parameters occurred
      after the treatment. There were no differences in tested parameters with the
      addition of S9 metabolic activation, indicating that atovaquone either has no
      metabolite or it is not toxic in the given concentrations. Since no effects were
      observed after the treatment, it is to be concluded that atovaquone is safe from
      the aspect of genototoxicity in the recommended dosages.

PMID- 21735455
TI  - Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma
      cell line.
AB  - Simvastatin is a competitive inhibitor of 3-hydroxymethylglutaryl coenzyme A
      reductase activity, whereas geraniol is a monoterpene with multiple pharmacologic
      effects on mevalonate metabolism. Both of them inhibit growth and proliferation
      of many cell lines. The present study was designed to determine the action of
      geraniol, in combination with simvastatin, by assessing their effects in vitro on
      human hepatocarcinoma cell line (Hep G2). The treatment of Hep G2 cells with
      concentrations of simvastatin or geraniol that did not inhibit cell proliferation
      (5 umol.l-1 of simvastatin and 50 umol.l-1 of geraniol) resulted in a significant
      inhibition of cell proliferation. We also examined the effect of simvastatin,
      geraniol and the combination of both on the biosynthesis of lipids from [14C]
      acetate. Our results demonstrate that the combination of simvastatin and geraniol
      synergistically inhibited cholesterol biosynthesis and proliferation of Hep G2
      cell line, contributing to a better understanding of the action of a component of
      essential oils targeting a complex metabolic pathway, which would improve the use
      of drugs or their combination in the fight against cancer and/or cardiovascular
      diseases.

PMID- 21735456
TI  - Routine enzymes in the monitoring of type 2 diabetes mellitus.
AB  - We examined the relationships of glucose and HbA1c levels with the routinely
      screened serum enzyme activities in type 2 diabetes mellitus, and we designed an
      in vitro study to evaluate the direct effect of glucose levels on enzyme
      activities. The study was performed on a consecutive series of outpatients with
      type 2 diabetes who were followed up at Dicle University Medical Faculty Hospital
      from May 2009 to May 2010 for the first time. Effects of aspartate transaminase,
      aminotransferase, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP),
      lactate dehydrogenase (LDH) activities, glucose and HbA1c levels and in vitro
      glucose (492, 287, 184, 131, 82 mg dl-1, respectively) on enzymes were
      determined. The patients were categorized on the basis of glucose and HbA1c
      levels and grouped according to a range of values. In patients with high HbA1c
      levels (>10.1%), ALP, GGT activities and creatine kinase (CK)-MB/CK (p = 0.008,
      0.026, 0.014) ratio were increased significantly when compared with those in the
      control group. In patients with high glucose levels (> 200 mg dl-1), ALP, GGT
      activities and CK-MB/CK ratio (p = 0.003, 0.001, 0.001) were increased
      significantly when compared with those in the control group. Glucose, which was
      added to serum in different concentrations in vitro, did not directly affect
      enzyme activities such as ALP, GGT and CK. We concluded that increased glucose
      levels could damage the liver and the heart muscle cells. Monitoring of blood
      glucose levels is a more valuable parameter than monitoring HbA1c in the
      momentary evaluation of diabetes.

PMID- 21735457
TI  - Ischaemia-modified albumin levels in newborn jaundice before and after
      phototherapy.
AB  - The aim of our study was to assess the effect of phototherapy (PT) on ischaemia
      modified albumin (IMA) and malondialdehyde (MDA) levels in hyperbilirubinemic
      full-term newborns. The study was performed on 36 full-term infants exposed to
      PT. The babies were aged 3 to 13 days. IMA and MDA levels of the babies were
      determined before and after PT, by a colorimetric assay. IMA levels before and
      after PT were found as 0.424 +/- 0.290 and 0.531 +/- 0.262 absorbance units,
      respectively. Although IMA levels after PT were slightly higher, the difference
      was not statistically significant (p > 0.131). MDA levels before and after PT
      were found as 8.4 +/- 1.8 umol/l and 9.4 +/- 1.5 umol/l, respectively. Serum MDA
      concentrations were significantly higher after PT than before PT (p < 0.000). In
      previous studies, conflicting findings have been reported about the effect of PT
      on oxidant and antioxidant systems. However, we have found no study investigating
      IMA levels in hyperbilirubinaemia in newborns before and after PT. Our results
      shows that PT does not affect IMA levels significantly. IMA increases as a result
      of oxidative stress. We believe that the lack of significant difference between
      our IMA levels before and after PT may resulted from hyperbilirubinaemia, which
      has antioxidant effect.

PMID- 21735458
TI  - Rapid validation of cancer genes in chimeras derived from established genetically
      engineered mouse models.
AB  - Recent technological advances have opened the door for the fast and cost
      effective generation of genetically engineered mouse models (GEMMs) to study
      cancer. We describe here a conceptually novel approach for the generation of
      chimeric GEMMs based on the controlled introduction of various genetic elements
      in embryonic stem cells (ESCs) that are derived from existing mouse strains with
      a predisposition for cancer. The isolation of GEMM-derived ESC lines is greatly
      facilitated by the availability of the newly defined culture media containing
      inhibitors that effectively preserve ESC pluripotency. The feasibility of the
      GEMM-ESC approach is discussed in light of current literature and placed into the
      context of existing models. This approach will allow for fast and flexible
      validation of candidate cancer genes and drug targets and will result in a
      repository of GEMM-ESC lines and corresponding vector collections that enable
      easy distribution and use of preclinical models to the wider scientific
      community.

PMID- 21735459
TI  - Are the Ro RNP-associated Y RNAs concealing microRNAs? Y RNA-derived miRNAs may
      be involved in autoimmunity.
AB  - Here we discuss the hypothesis that the RNA components of the Ro
      ribonucleoproteins (RNPs), the Y RNAs, can be processed into microRNAs (miRNAs).
      Although Ro RNPs, whose main protein components Ro60 and La are targeted by the
      immune system in several autoimmune diseases, were discovered many years ago,
      their function is still poorly understood. Indeed, recent data show that miRNA
      sized small RNAs can be generated from Y RNAs. This hypothesis leads also to a
      model in which Ro60 acts as a modulator in the Y RNA-derived miRNA biogenesis
      pathway. The implications of these Y RNA-derived miRNAs, which may be
      specifically produced under pathological circumstances such as in autoimmunity or
      during viral infections, for the enigmatic function of Ro RNPs are discussed.

PMID- 21735460
TI  - Response to "The tissue organization field theory of cancer: a testable
      replacement for the somatic mutation theory". DOI: 10.1002/bies.201100025.

PMID- 21735461
TI  - Response to "In defense of the somatic mutation theory of cancer". DOI:
      10.1002/bies.201100022.

PMID- 21735462
TI  - Liquid chromatography-tandem mass spectrometry for quantification of lacosamide,
      an antiepileptic drug, in rat plasma and its application to pharmacokinetic
      study.
AB  - A rapid, simple and sensitive liquid chromatography-tandem mass spectrometry
      (LC/MS/MS) was developed for the determination of an antiepileptic drug,
      lacosamide, in rat plasma. The method involves the addition of acetonitrile and
      internal standard solution to plasma samples, followed by centrifugation. An
      aliquot of the supernatant was diluted with water and directly injected into the
      LC/MS/MS system. The separations were performed on column packed with
      octadecylsilica (5 um, 2.0 * 50 mm) with 0.1% formic acid and acetonitrile as
      mobile phase, and the detection was performed on tandem mass spectrometry by the
      multiple-reaction monitoring via an electrospray ionization source. The standard
      curve was linear over the concentration range from 0.3 to 1000 ng/mL. The lower
      limit of quantification was 0.3 ng/mL using 50 MUL of rat plasma sample. The
      intra- and inter-assay precision and accuracy were found to be less than 11.7 and
      8.8%, respectively. The developed analytical method was successfully applied to
      the pharmacokinetic study of lacosamide in rats.

PMID- 21735463
TI  - Terlipressin: an asset for hepatologists!

PMID- 21735465
TI  - Clinical correlation of miR-375 and alpha-fetoprotein in hepatocellular
      carcinoma: comparison in mice and humans.

PMID- 21735466
TI  - Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in
      facilitating entry into hepatocytes.
AB  - Our previous studies demonstrated that hepatitis C virus (HCV) envelope
      glycoproteins 1 and 2 (E1 and E2) display distinct reactivity to different cell
      surface molecules. In this study, we characterized the interaction of E1 and E2
      with apolipoproteins in facilitating virus entry. The results suggested a higher
      neutralization of vesicular stomatitis virus (VSV)/HCV E1-G pseudotype
      infectivity by antibodies to apolipoprotein E (ApoE) than apolipoprotein B
      (ApoB), with VSV/HCV E2-G pseudotype infectivity remaining largely unaffected.
      Neutralization of cell-culture-grown HCV infectivity by antiserum to ApoE and, to
      a lesser extent, by ApoB further verified their involvement in virus entry. HCV
      E1, but not E2, displayed binding with ApoE and ApoB by enzyme-linked
      immunosorbent assay. Binding of E1 with apolipoproteins were further supported by
      coimmunoprecipitation from human hepatocytes expressing E1. Rabbit antiserum to a
      selected E1 ectodomain-derived peptide displayed ~ 50% neutralization of E1-G
      pseudotype infectivity. Furthermore, E1 ectodomain-derived synthetic peptides
      significantly inhibited the interaction of E1 with both the apolipoproteins.
      Investigation on the role of low-density lipoprotein receptor (LDL-R) as a
      hepatocyte surface receptor for virus entry suggested a significant reduction in
      E1-G pseudotype plaque numbers (~ 70%) by inhibiting LDL-R ligand-binding
      activity using human proprotein convertase subtilisin/kexin type 9 and platelet
      factor-4, whereas they had a minimal inhibitory effect on the E2-G pseudotype.
      CONCLUSION: Together, the results suggested an association between HCV E1 and
      apolipoproteins, which may facilitate virus entry through LDL-R into mammalian
      cells.

PMID- 21735467
TI  - Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating
      Kupffer cell polarization in mice.
AB  - Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic
      liver disease. Because cannabinoid CB2 receptors (CB2) display potent anti
      inflammatory properties, we investigated their role in the pathogenesis of
      alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell
      polarization and the consequences on liver steatosis. Wild-type (WT) mice fed an
      alcohol diet showed an induction of hepatic classical (M1) and alternative (M2)
      markers. Cotreatment of alcohol-fed mice with the CB2 agonist, JWH-133, decreased
      hepatic M1 gene expression without affecting the M2 profile. In keeping with
      this, genetic ablation of CB2 enhanced hepatic induction of M1 gene signature and
      blunted the induction of M2 markers. CB2 also modulated alcohol-induced fatty
      liver, as shown by the reduction of hepatocyte steatosis in JWH-133-treated mice
      and its enhancement in CB2-/- animals. Studies in isolated Kupffer cells and
      cultured macrophages further demonstrated that CB2 inhibits M1 polarization and
      favors the transition to an M2 phenotype. In addition, conditioned-medium
      experiments showed that preventing M1 polarization in CB2-activated macrophages
      protects from lipid accumulation in hepatocytes. Heme oxygenase-1 (HO-1) mediated
      the anti-inflammatory effects of CB2 receptors. Indeed, alcohol-fed mice treated
      with JWH-133 showed increased hepatic expression of macrophage HO-1, as compared
      to vehicle-treated counterparts. In keeping with this, JWH-133 induced HO-1
      expression in cultured macrophages, and the HO-1 inhibitor, zinc protoporphyrin,
      blunted the inhibitory effect of JWH-133 on lipopolysaccharide-induced nuclear
      factor-kappa B activation and M1 polarization. Altogether, these findings
      demonstrate that CB2 receptors display beneficial effects on alcohol-induced
      inflammation by regulating M1/M2 balance in Kupffer cells, thereby reducing
      hepatocyte steatosis via paracrine interactions between Kupffer cells and
      hepatocytes. These data identify CB2 agonists as potential therapeutic agents for
      the management of alcoholic liver disease.

PMID- 21735468
TI  - The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates
      hepatic inflammatory response through antagonizing nuclear factor kappa light
      chain enhancer of activated B cells (NF-kappaB) in mice.
AB  - Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well known for its roles
      in regulation of energy homeostasis and glucose metabolism. TGR5 also displays
      strong attenuation of macrophage reactivity in vitro, but the physiological roles
      of TGR5 in inflammatory response, and its mechanism, is unknown. Here, we
      demonstrate that TGR5 is a negative modulator of nuclear factor kappa light-chain
      enhancer of activated B cells (NF-kappaB)-mediated inflammation. TGR5 activation
      suppresses the phosphorylation of nuclear factor of kappa light polypeptide gene
      enhancer in B-cells inhibitor, alpha (IkappaBalpha), the translocation of p65, NF
      kappaB DNA-binding activity, and its transcription activity. Furthermore, TGR5
      activation enhances the interaction of IkappaBalpha and beta-arrestin2.
      Suppression of NF-kappaB transcription activity and its target gene expression by
      TGR5 agonist are specifically abolished by the expression of anti-beta-arrestin2
      small interfering RNA. These results show that TGR5 suppresses the NF-kappaB
      pathway by mediation of the interaction between IkappaBalpha and beta-arrestin2.
      In a lipopolysaccharide (LPS)-induced inflammation model, TGR5(-/-) mice show
      more severe liver necroses and inflammation, compared with wild-type (WT) mice.
      Activation of TGR5 by its agonist ligand inhibits the expression of inflammatory
      mediators in response to NF-kappaB activation induced by LPS in WT, but not TGR5(
      /-), mouse liver. CONCLUSION: These findings identify TGR5 as a negative mediator
      of inflammation that may serve as an attractive therapeutic tool for immune and
      inflammatory liver diseases.

PMID- 21735469
TI  - Fine phenotypic and functional characterization of effector cluster of
      differentiation 8 positive T cells in human patients with primary biliary
      cirrhosis.
AB  - In primary biliary cirrhosis (PBC), patients develop a multilineage response to a
      highly restricted peptide of the E2 component of pyruvate dehydrogenase (PDC-E2)
      involving autoantibody and autoreactive cluster of differentiation (CD)4(+) and
      CD8(+) T-cell responses. Recent data from murine models have suggested that liver
      infiltrating CD8(+) cells play a critical role in biliary destruction in PBC. We
      hypothesized that chronic antigen stimulation of CD8(+) T cells alters effector
      memory T cell (T(EM) ) frequency and function similar to that seen with chronic
      viral infections, including failure to terminally differentiate and relative
      resistance to apoptosis. We have rigorously phenotyped CD8(+) T-cell
      subpopulations from 132 subjects, including 76 patients with PBC and 56 controls,
      and report a higher frequency of T(EM) cells characterized as CD45RO(high)
      CD57(+) CD8(high), but expressing the gut homing integrin, alpha4beta7, in
      peripheral blood mononuclear cells of PBC. These CD8(high) T(EM) cells have
      reduced expression of Annexin V after TCR stimulation. Consistent with a T(EM)
      phenotype, CD45RO(high) CD57(+) CD8(high) T cells express higher levels of
      granzyme A, granzyme B, perforin, CCR5 and alpha4beta7, and lower levels of CCR7
      and CD28 than other CD8(high) T cells. Furthermore, interleukin (IL)-5 produced
      by CD8(+) CD57(+) T lymphocytes upon in vitro T-cell receptor stimulation are
      increased in PBC. Histologically, CD8(+) CD57(+) T cells accumulate around the
      portal area in PBC. Moreover, CD8(+) CD57(+) T cells respond specifically to the
      major histocompatibility class I epitope of PDC-E2. CONCLUSION: In conclusion,
      our data demonstrate that CD45RO(high) CD57(+) CD8(high) T cells are a subset of
      terminally differentiated cytotoxic T(EM) cells, which could play a critical role
      in the progressive destruction of biliary epithelial cells.

PMID- 21735470
TI  - Drug-Induced liver injury with hypersensitivity features has a better outcome: a
      single-center experience of 39 children and adolescents.
AB  - Drug-induced liver injury (DILI) is rare in children and adolescents, and,
      consequently, data are remarkably limited. We analyzed the causes, clinical and
      biochemical features, natural history, and outcomes of children with DILI.
      Consecutive children with DILI from 1997 to 2004 (retrospective) and 2005 to 2010
      (prospective) were studied based on standard criteria for DILI. Thirty-nine
      children constituted 8.7% of 450 cases of DILI. There were 22 boys and 17 girls.
      Median age was 16 years (range, 2.6-17). Combination antituberculous drugs were
      the most common cause (n = 22), followed by the anticonvulsants, phenytoin (n =
      10) and carbamazepine (n = 6). All of the 16 children (41%) who developed
      hypersensitivity features, such as skin rashes, fever, lymphadenopathy, and/or
      eosinophilia, including the 3 with Stevens-Johnson syndrome, survived. Those with
      hypersensitivity presented earlier (24.5 versus 35 days; P = 0.24) had less
      severe disease (MELD, 16 versus 29; P = 0.01) and had no mortality (0/16 versus
      12/23; P < 0.001), compared to those without hypersensitivity. The 12 fatalities
      were largely the result of antituberculous DILI (n = 11). The presence of
      encephalopathy and ascites were associated with mortality, along with
      hyperbilirubinemia, high international normalized ratio, and serum creatinine.
      According to the Roussel Uclaf Causality Assessment Method, 18 were highly
      probable, 14 probable, and 7 possible. Thirty-two children were hospitalized.
      CONCLUSION: DILI is not uncommon in children and accounts for 8.7% of all
      patients with DILI. Antituberculous drugs and anticonvulsants are the leading
      causes of DILI in India. Overall mortality is high (30.7%), largely accounted by
      antituberculous drugs. Children with DILI and hypersensitivity features present
      early, have less severe disease, and, consequently, a better prognosis, compared
      to those without, and are often associated with anticonvulsants or sulfonamides.

PMID- 21735471
TI  - Occult hepatitis B virus infection: bit player or role player?

PMID- 21735472
TI  - Novel feedback inhibition of surface antigen synthesis by mammalian target of
      rapamycin (mTOR) signal and its implication for hepatitis B virus tumorigenesis
      and therapy.
AB  - Ground glass hepatocytes (GGHs) harboring hepatitis B virus (HBV) pre-S mutants
      have been recognized as precursor lesions of hepatocellular carcinoma (HCC).
      Previously, we observed the activation of mammalian target of rapamycin (mTOR) in
      GGHs and HCCs, together with a decreased expression of HBV surface antigen
      (HBsAg) in HCC tissues. It is, therefore, hypothesized that the activation of
      mTOR during HBV tumorigenesis may potentially down-regulate HBsAg expression. In
      this study, we verified an inverse relationship between the expression of HBsAg
      and phosphorylated mTOR (p-mTOR) in 13 of 20 paired nontumorous liver and HCC
      tissues. In vitro, wild-type or mutant pre-S proteins could activate mTOR in the
      HuH-7 cell line. Interestingly, the up-regulated mTOR, in turn, suppressed HBsAg
      synthesis at the transcriptional level via the transcription factor, Yin Yang 1
      (YY1), which bound to nucleotide 2812-2816 of the pre-S1 promoter. This
      inhibitory effect by the mTOR signal could be abolished by the knockdown of
      histone deacetylase 1 (HDAC1). Furthermore, YY1 was physically associated with
      HDAC1 in a manner dependent on mTOR activation. Collectively, pre-S protein
      induced mTOR activation may recruit the YY1-HDAC1 complex to feedback suppress
      transcription from the pre-S1 promoter. CONCLUSION: The activation of mTOR signal
      in GGHs may feedback suppress HBsAg synthesis during HBV tumorigenesis and
      explain the observed decrease or absence of HBsAg in HCC tissues. Therapy using
      mTOR inhibitors for HCCs may potentially activate HBV replication in patients
      with chronic HBV infection.

PMID- 21735473
TI  - Gankyrin-mediated dedifferentiation facilitates the tumorigenicity of rat
      hepatocytes and hepatoma cells.
AB  - Gankyrin is a critical oncoprotein overexpressed in human hepatocellular
      carcinoma (HCC). However, the mechanism underlying gankyrin-mediated
      hepatocarcinogenesis remains elusive. Herein, we provide evidence that gankyrin
      expression was progressively elevated in liver fibrosis, cirrhosis, and HCC.
      Levels of gankyrin expression were closely associated with the dedifferentiation
      status of hepatoma in patients. Decrease of hepatocyte characteristic markers and
      increase of cholangiocyte-specific markers were observed in rat primary
      hepatocytes with enforced gankyrin expression and diethylnitrosamine (DEN)
      triggered rat hepatocarcinogenesis. Overexpression of gankyrin also attenuated
      the hepatic function of primary hepatocytes, which further suggests that gankyrin
      promotes the dedifferentiation of hepatocytes. Moreover, elevated expression of
      gankyrin closely correlated with the expression of HCC stem/progenitor cell
      markers in DEN-triggered hepatocarcinogenesis and human HCCs. Hepatoma cells
      derived from suspension-cultured spheroids exhibited a higher gankyrin level, and
      enforced gankyrin expression in hepatoma cells remarkably enhanced cluster of
      differentiation (CD)133, CD90, and epithelial cellular adhesion molecule
      expression, indicating a role of gankyrin in hepatoma cell dedifferentiation and
      the generation of hepatoma stem/progenitor cells. In contrast, down-regulation of
      gankyrin in hepatoma cells by lentivirus-mediated microRNA delivery significantly
      improved their differentiation status and attenuated malignancy. Interference of
      gankyrin expression in hepatoma cells also diminished the proportion of cancer
      stem/progenitor cells and their self-renewal capacity. Furthermore, gankyrin was
      found to bind hepatocyte nuclear factor 4alpha (HNF4alpha), which determines
      hepatocyte differentiation status and enhances proteasome-dependent HNF4alpha
      degradation in hepatoma cells. The inverse correlation of gankyrin and HNF4alpha
      was further confirmed in primary hepatocytes, DEN-induced hepatocarcinogenesis,
      and human HCCs. CONCLUSION: Gankyrin-mediated dedifferentiation of hepatocytes
      and hepatoma cells via, at least partially, down-regulation of HNF4alpha
      facilitates HCC development, and interference of gankyrin expression could be a
      novel strategy for HCC prevention and differentiation therapy.

PMID- 21735474
TI  - Comparison of osmotic swelling influences on meniscal fibrocartilage and
      articular cartilage tissue mechanics in compression and shear.
AB  - Although the contribution of the circumferential collagen bundles to the
      anisotropic tensile stiffness of meniscal tissue has been well described, the
      implications of interactions between tissue components for other mechanical
      properties have not been as widely examined. This study compared the effects of
      the proteoglycan-associated osmotic swelling stress on meniscal fibrocartilage
      and articular cartilage (AC) mechanics by manipulating the osmotic environment
      and tissue compressive offset. Cylindrical samples were obtained from the menisci
      and AC of bovine stifles, equilibrated in phosphate-buffered saline solutions
      ranging from 0.1* to 10*, and tested in oscillatory torsional shear and
      unconfined compression. Biochemical analysis indicated that treatments and
      testing did not substantially alter tissue composition. Mechanical testing
      revealed tissue-specific responses to both increasing compressive offset and
      decreasing bath salinity. Most notably, reduced salinity dramatically increased
      the shear modulus of both axially and circumferentially oriented meniscal tissue
      explants to a much greater extent than for cartilage samples. Combined with
      previous studies, these findings suggest that meniscal proteoglycans have a
      distinct structural role, stabilizing, and stiffening the matrix surrounding the
      primary circumferential collagen bundles.

PMID- 21735475
TI  - Bone remodeling in postmenopausal women who discontinued denosumab treatment: off
      treatment biopsy study.
AB  - Denosumab is a fully human monoclonal antibody that neutralizes the activity of
      RANKL, leading to the inhibition of osteoclast maturation, bone-resorbing
      activity, and survival. Evaluation of trans-iliac crest bone biopsy specimens in
      the phase 3 pivotal fracture study with denosumab in postmenopausal women with
      osteoporosis showed evidence of reduced bone turnover at the tissue level in
      subjects receiving denosumab, and up to one-third of subjects did not have
      evidence of tetracycline labeling in trabecular or cortical bone. Discontinuation
      of denosumab therapy has demonstrated that the effects of denosumab are
      reversible, as assessed by biochemical markers of bone turnover (BTM) and BMD.
      The precise nature of changes that occur at the tissue level with denosumab
      discontinuation have not been explored. Fifteen subjects were enrolled in a
      cohort study to evaluate the effects of denosumab discontinuation at the tissue
      level. Subjects had discontinued osteoporosis treatment for a mean time of 25.1
      months (range 21 to 29 months). Bone histomorphometry results were compared with
      results from placebo-treated women with osteoporosis in the denosumab phase 3
      pivotal fracture bone biopsy substudy, and BTMs were compared with subjects'
      pretreatment values. The results of this study showed normal histology and bone
      remodeling similar to those observed in untreated postmenopausal women with
      osteoporosis. With treatment cessation, 100% of biopsy specimens had evidence of
      tetracycline labels. Biochemical markers were comparable to and highly correlated
      with pretreatment levels. These data confirm that the effects of denosumab on
      bone turnover at the tissue level are fully reversible.

PMID- 21735476
TI  - PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure
      in hypoparathyroidism.
AB  - Hypoparathyroidism is associated with abnormal structural and dynamic skeletal
      properties. We hypothesized that parathyroid hormone(1-84) [PTH(1-84)] treatment
      would restore skeletal properties toward normal in hypoparathyroidism. Sixty-four
      subjects with hypoparathyroidism were treated with PTH(1-84) for 2 years. All
      subjects underwent histomorphometric assessment with percutaneous iliac crest
      bone biopsies. Biopsies were performed at baseline and at 1 or 2 years. Another
      group of subjects had a single biopsy at 3 months, having received tetracycline
      before beginning PTH(1-84) and prior to the biopsy (quadruple-label protocol).
      Measurement of biochemical bone turnover markers was performed. Structural
      changes after PTH(1-84) included reduced trabecular width (144 +/- 34 um to 128
      +/- 34 um, p = 0.03) and increases in trabecular number (1.74 +/- 0.34/mm to 2.07
      +/- 0.50/mm, p = 0.02) at 2 years. Cortical porosity increased at 2 years (7.4%
      +/- 3.2% to 9.2% +/- 2.4%, p = 0.03). Histomorphometrically measured dynamic
      parameters, including mineralizing surface, increased significantly at 3 months,
      peaking at 1 year (0.7% +/- 0.6% to 7.1% +/- 6.0%, p = 0.001) and persisting at 2
      years. Biochemical measurements of bone turnover increased significantly, peaking
      at 5 to 9 months of therapy and persisting for 24 months. It is concluded that
      PTH(1-84) treatment of hypoparathyroidism is associated with increases in
      histomorphometric and biochemical indices of skeletal dynamics. Structural
      changes are consistent with an increased remodeling rate in both trabecular and
      cortical compartments with tunneling resorption in the former. These changes
      suggest that PTH(1-84) improves abnormal skeletal properties in
      hypoparathyroidism and restores bone metabolism toward normal euparathyroid
      levels.

PMID- 21735477
TI  - Epigenetic regulation of osteoclast differentiation: possible involvement of
      Jmjd3 in the histone demethylation of Nfatc1.
AB  - Gene expression is controlled by epigenetic mechanisms such as histone
      acetylation and methylation, and recent studies have revealed that key
      developmental steps are regulated by the trimethylation of histone H3 lysine 4
      (H3K4me3) and lysine 27 (H3K27me3). Using ChIP sequencing technology combined
      with real-time PCR, we here demonstrate that the H3K27me3 observed in the Nfatc1
      gene in bone marrow-derived macrophages (BMMs) was markedly reduced in mature
      osteoclasts. Jumonji domain-containing 3 (Jmjd3), a H3K27 demethylase, was
      induced in bone marrow-derived macrophages and in the vicinity of the
      transcription start site (TSS) of nuclear factor-activated T cells (NFAT) c1 in
      response to receptor activator of nuclear factor-kappaB ligand (RANKL)
      stimulation. Gene silencing of the Jmjd3 gene by short hairpin RNA reduced
      demethylation of H3K27me3 at the TSS of Nfatc1 and suppressed RANKL-induced
      osteoclastogenesis. These results suggest that the demethylation of H3K27me3 in
      the Nfatc1 gene locus by Jmjd3 plays a critical role in RANKL-induced osteoclast
      differentiation.

PMID- 21735478
TI  - Cell line IDG-SW3 replicates osteoblast-to-late-osteocyte differentiation in
      vitro and accelerates bone formation in vivo.
AB  - Osteocytes are the most abundant cells in bone yet are the most challenging to
      study because they are embedded in a mineralized matrix. We generated a clonal
      cell line called IDG-SW3 (for Immortomouse/Dmp1-GFP-SW3) from long-bone chips
      from mice carrying a Dmp1 promoter driving GFP crossed with the Immortomouse,
      which expresses a thermolabile SV40 large T antigen regulated by interferon gamma
      (IFN-gamma). Cells from these mice can be expanded at 33  degrees C in the
      presence of IFN-gamma and then allowed to resume their original phenotype at 37 
      degrees C in the absence of IFN-gamma. IDG-SW3 cells are Dmp1-GFP(-) and T
      antigen(+) under immortalizing conditions but Dmp1-GFP(+) and T antigen(-) under
      osteogenic conditions. Like osteoblasts, they express alkaline phosphatase and
      produce and mineralize a type 1 collagen matrix containing calcospherulites. Like
      early osteocytes, they express E11/gp38, Dmp1, MEPE, and Phex. Like late
      osteocytes, they develop a dendritic morphology and express SOST/sclerostin and
      fibroblast growth factor 23 (FGF-23), regulated by parathyroid hormone (PTH) and
      1,25-dihydroxyvitamin D(3). When cultured on 3D matrices, they express Dmp1-GFP
      and sclerostin. When the 3D cultures are implanted in calvarial defects in vivo,
      they accelerate bone healing. This cell line should prove useful for studying
      osteoblast-to-osteocyte transition, mechanisms for biomineralization, osteocyte
      function, and regulation of SOST/sclerostin and FGF-23.

PMID- 21735479
TI  - Early-onset tardive dyskinesia in a neuroleptic-naive patient exposed to low-dose
      quetiapine.

PMID- 21735480
TI  - Health-related quality-of-life scales in Parkinson's disease: critique and
      recommendations.
AB  - Health-related quality of life is an important patient-reported outcome used in
      intervention trials and for monitoring the consequences of health status on
      physical, mental, and social domains. Parkinson's disease is a complex disorder
      that strongly affects patients' quality of life. Several health-related quality
      of life tools have been used in Parkinson's disease. A Movement Disorder Society
      Task Force was commissioned to rate the psychometric quality of available health
      related quality of life scales as applied to Parkinson's disease. Following the
      methodology adopted by previous work of the Movement Disorder Society Task Force,
      a review of generic and specific health-related quality of life scales applied in
      studies on Parkinson's disease was completed. Considering the scales from 3
      perspectives-use in Parkinson's disease, use by multiple research groups, and
      clinimetric properties-a final classification as "recommended," "suggested," or
      "listed" was applied to each reviewed instrument. Four generic scales (EuroQoL,
      Nottingham Health Profile, 36-Item Short-Form Health Survey, and Sickness Impact
      Profile) and 5 specific scales (39-Item Parkinson's Disease Questionnaire,
      Parkinson's Disease Questionnaire Short Form, Parkinson's Disease Quality of Life
      Questionnaire, Parkinson's Impact Scale, and Scales for Outcomes in Parkinson's
      Disease-Psychosocial) reached the level of "recommended." The 39-item Parkinson's
      Disease Questionnaire is the most thoroughly tested and applied questionnaire.
      Three other generic measures (Quality of Life Questionnaire 15D, Schedule for the
      Evaluation of Individual Quality of Life-Direct Weighting, and World Health
      Organization Quality of Life Assessment Short Version) and the specific
      Parkinson's Disease Quality of Life Scale are "suggested." With a little
      additional effort in completing the stipulated requirements, they could reach the
      "recommended" level. At present there is a wide variety of health-related quality
      of life measures for application in the Parkinson's disease setting, and the task
      force does not recommend the development of a new scale. Selection of the most
      appropriate instrument for a particular objective requires consideration of the
      characteristics of each scale and the goals of the assessment.

PMID- 21735481
TI  - Arm tremor in cervical dystonia--is it a manifestation of dystonia or essential
      tremor?
AB  - The classification of arm tremor in cervical dystonia is a controversial issue.
      There have been many, at times passionate disputes in the movement disorder
      community about whether it should be classified as a manifestation of dystonia or
      essential tremor associated with dystonia. There are arguments in favor of both
      views. Settling the issue might be relevant to the understanding of the
      etiological, presumably genetic, background because phenomenological grouping is
      the starting point for genetic analyses. From this point of view, we outline this
      tremor debate and add some new clinical data.

PMID- 21735482
TI  - Hypersexuality and pathological gambling in Parkinson's disease: A cross
      sectional case-control study.
AB  - BACKGROUND: Substance and behavioral addictions have already been described
      separately or in combination in Parkinson's disease. However, no comparisons of
      the prevalence of addictive behaviors in patients with Parkinson's disease and
      the general population have been published. The objective of this study was to
      compare the prevalence and characteristics of addictions (gambling,
      hypersexuality, tobacco, and alcohol) in patients with Parkinson's disease and in
      a matched, paired sample from the general population. METHODS: After matching for
      age, sex, and complete field questionnaires on addictions, we had 115 data sets.
      RESULTS: No difference was observed between Parkinson's disease and control
      populations concerning pathological gambling (0.87% vs 0.87%, P = .99), tobacco
      addiction (1.7% vs 1.7%, P = .99), and alcohol dependence (2.6% vs 3.5%, P =
      .71). The Parkinson's disease group showed 2 cases of sexual addiction (1.7% vs
      0, P = .15). CONCLUSIONS: Our results indicate that patients with Parkinson's
      disease do not have specific profiles for tobacco or alcohol addiction and
      pathological gambling compared with the general population.

PMID- 21735483
TI  - The curious case of phenocopies in families with genetic Parkinson's disease.
AB  - Monogenic forms of Parkinson's disease account for ~3% of all "idiopathic"
      Parkinson's disease. With reduced penetrance in dominant forms and manifesting
      heterozygotes in recessive forms of Parkinson's disease, it has been well
      recognized that inheritance patterns do not always follow classic Mendelian
      genetics. A novel twist to the puzzle is the presence of phenocopies (i.e.,
      family members with the same clinical syndrome as the mutation carriers, but
      lacking the familial mutation). We reviewed all pedigrees published between 1997
      and 2009 with alpha-synuclein, leucine-rich repeat kinase 2, Parkin, or PTEN
      induced kinase 1 mutations with at least 2 affected individuals and known genetic
      status for the possible presence of phenocopies. Of 537 patients with clinical
      Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients
      (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of
      all blood relatives reported in the pedigrees containing phenocopies and an
      estimated 1.3% of all blood relatives in all pedigrees included. Both of these
      rates exceeded age-specific prevalences of Parkinson's disease. In 4 families,
      the phenocopy was explained by another known mutation: In 2 pedigrees, a
      monogenic cause was likely; in another 2, secondary parkinsonism was suspected;
      and in the remaining 15 families, "sporadic Parkinson's disease" was suggested as
      the cause of disease in the phenocopy. The unexpectedly high number of
      phenocopies of mostly unknown origin within families with a seemingly known
      etiology of Parkinson's disease adds another level of complexity to genetic
      research of Parkinson's disease, as well as to the interpretation of genetic
      testing results in the clinical diagnostic setting.

PMID- 21735484
TI  - KFC2: a knowledge-based hot spot prediction method based on interface solvation,
      atomic density, and plasticity features.
AB  - Hot spots constitute a small fraction of protein-protein interface residues, yet
      they account for a large fraction of the binding affinity. Based on our previous
      method (KFC), we present two new methods (KFC2a and KFC2b) that outperform other
      methods at hot spot prediction. A number of improvements were made in developing
      these new methods. First, we created a training data set that contained a similar
      number of hot spot and non-hot spot residues. In addition, we generated 47
      different features, and different numbers of features were used to train the
      models to avoid over-fitting. Finally, two feature combinations were selected:
      One (used in KFC2a) is composed of eight features that are mainly related to
      solvent accessible surface area and local plasticity; the other (KFC2b) is
      composed of seven features, only two of which are identical to those used in
      KFC2a. The two models were built using support vector machines (SVM). The two
      KFC2 models were then tested on a mixed independent test set, and compared with
      other methods such as Robetta, FOLDEF, HotPoint, MINERVA, and KFC. KFC2a showed
      the highest predictive accuracy for hot spot residues (True Positive Rate: TPR =
      0.85); however, the false positive rate was somewhat higher than for other
      models. KFC2b showed the best predictive accuracy for hot spot residues (True
      Positive Rate: TPR = 0.62) among all methods other than KFC2a, and the False
      Positive Rate (FPR = 0.15) was comparable with other highly predictive methods.

PMID- 21735486
TI  - Low-power flexible organic light-emitting diode display device.

PMID- 21735487
TI  - Hydrophilic flower-like CuS superstructures as an efficient 980 nm laser-driven
      photothermal agent for ablation of cancer cells.

PMID- 21735488
TI  - Self-heating and external strain coupling induced phase transition of VO2
      nanobeam as single domain switch.

PMID- 21735489
TI  - Three-dimensional directed assembly of block copolymers together with two
      dimensional square and rectangular nanolithography.

PMID- 21735490
TI  - Crystal growth of clathrate hydrate in gas/liquid/liquid system: variations in
      crystal-growth behavior.
AB  - This paper reports the visual observations of the formation and growth of
      structure-II hydrate crystals on a water droplet partially immersed in liquid
      cyclopentane and exposed to difluoromethane gas. Each of the experiments was
      performed under prescribed temperature and pressure conditions in the range from
      281.7 to 297.0 K and from 0.12 to 1.10 MPa in order to investigate the effect of
      the driving force for the hydrate crystal growth. The experiments were conducted
      at 25 different temperature-pressure conditions. It was found that the behavior
      of the hydrate crystal growth in this three-component system can be classified
      into three modes, which we called "cover", "expansion" and "line", depending on
      the temperature and pressure. The descriptions of the three types are summarized
      as follows. "COVER": Hydrate crystals first formed on the water-droplet surface
      and then grew to form a polycrystalline layer covering the surface. After
      complete surface coverage, no more hydrate growth and little change in the shape
      of the hydrate-covered water droplet were observed. "EXPANSION": Like "cover",
      the first crystals were observed on the water-droplet surface. They grew not only
      along the surface, but also toward the gas phase, and then continued to grow for
      more than several tens of minutes after complete coverage. "LINE": Unlike the
      other two modes, hydrate crystals first formed at the three-phase interfacial
      line and grew along this line. The shape of the hydrate crystals eventually
      became like a doughnut, since the center of the water droplet collapsed when they
      grew.

PMID- 21735491
TI  - Excellent correlation between drug release and portal size in metalla-cage drug
      delivery systems.
AB  - A series of large cationic hexanuclear metalla-prisms, [Ru(6)(p
      iPrC(6)H(4)Me)(6)(tpt)(2)(donq)(3)](6+), [Ru(6)(p
      iPrC(6)H(4)Me)(6)(tpt)(2)(doaq)(3)](6+) and [Ru(6)(p
      iPrC(6)H(4)Me)(6)(tpt)(2)(dotq)(3)](6+), composed of p-cymene-ruthenium building
      blocks bridged by OO?OO ligands (donq=5,8-dioxido-1,4-naphthoquinonato; doaq=5,8
      dioxido-1,4-anthraquinonato, dotq=6,11-dioxido-5,12-naphthacenedionato) and
      connected by two 2,4,6-tripyridin-4-yl-1,3,5-triazine (tpt) panels, which
      encapsulate the guest molecules 1-(4,6-dichloro-1,3,5-triazin-2-yl)pyrene and
      Pd(acac)(2), have been prepared. The host-guest properties of these water-soluble
      delivery systems were studied in solution by NMR and fluorescence spectroscopy,
      providing the stability constants (K) for these host-guest systems. Moreover, the
      ability of the hosts to deliver the guests into cancer cells was evaluated and
      the uptake mechanism studied; the rate of release of the guest molecule was found
      to depend on the portal size of the host.

PMID- 21735492
TI  - Mechanistic studies of Fc-PNA(?DNA) surface dynamics based on the kinetics of
      electron-transfer processes.
AB  - N-Terminally ferrocenylated and C-terminally gold-surface-grafted peptide nucleic
      acid (PNA) strands were exploited as unique tools for the electrochemical
      investigation of the strand dynamics of short PNA(?DNA) duplexes. On the basis of
      the quantitative analysis of the kinetics and the diffusional characteristics of
      the electron-transfer process, a nanoscopic view of the Fc-PNA(?DNA) surface
      dynamics was obtained. Loosely packed, surface-confined Fc-PNA single strands
      were found to render the charge-transfer process of the tethered Fc moiety
      diffusion-limited, whereas surfaces modified with Fc-PNA?DNA duplexes exhibited a
      charge-transfer process with characteristics between the two extremes of
      diffusion and surface limitation. The interplay between the inherent strand
      elasticity and effects exerted by the electric field are supposed to dictate the
      probability of a sufficient approach of the Fc head group to the electrode
      surface, as reflected in the measured values of the electron-transfer rate
      constant, k(0). An in-depth understanding of the dynamics of surface-bound PNA
      and PNA?DNA strands is of utmost importance for the development of DNA biosensors
      using (Fc-)PNA recognition layers.

PMID- 21735493
TI  - The experimental realization of a neutral homoaromatic carbocycle.
AB  - Infrared spectra recorded for 1,5-dimethyl-2,8:4,6-semibullvalenetetracarboxylic
      acid dianhydride (12) in the condensed and vapor phase clearly prove that in the
      vapor phase the dianhydride 12 is a homoaromatic ground state semibullvalene.

PMID- 21735494
TI  - Selective photocatalytic oxidation of alcohols to aldehydes in water by TiO2
      partially coated with WO3.
AB  - Semiconductor TiO(2) particles loaded with WO(3) (WO(3)/TiO(2)), synthesized by
      impregnation of tungstic acid followed by calcination, were used for
      photocatalytic oxidation of alcohols in water with molecular oxygen under
      irradiation at lambda>350 nm. The WO(3)/TiO(2) catalysts promote selective
      oxidation of alcohols to aldehydes and show higher catalytic activity than pure
      TiO(2). In particular, a catalyst loading 7.6 wt % WO(3) led to higher aldehyde
      selectivity than previously reported photocatalytic systems. The high aldehyde
      selectivity arises because subsequent photocatalytic decomposition of the formed
      aldehyde is suppressed on the catalyst. The TiO(2) surface of the catalyst, which
      is active for oxidation, is partially coated by the WO(3) layer, which leads to a
      decrease in the amount of formed aldehyde adsorbed on the TiO(2) surface. This
      suppresses subsequent decomposition of the aldehyde on the TiO(2) surface and
      results in high aldehyde selectivity. The WO(3)/TiO(2) catalyst can selectively
      oxidize various aromatic alcohols and is reusable without loss of catalytic
      activity or selectivity.

PMID- 21735495
TI  - The role of oxidative etching in the synthesis of ultrathin single-crystalline Au
      nanowires.
AB  - The fabrication of ultrathin single-crystal Au nanowires with high aspect ratio
      and that are stable in air is challenging. Recently, a simple wet-chemical
      approach using oleylamine has been reported for the synthesis of Au nanowires
      with micrometer length and 2 nm in diameter. Despite efforts to understand the
      mechanism of the reaction, an ultimate question about the role of oxygen (O(2))
      during the synthesis remained unclear. Here we report that the synthesis of
      ultrathin Au nanowires employing oleylamine is strongly affected by the amount of
      O(2) absorbed in the reaction solution. Saturating the solution with O(2) leads
      to both a high-yield production of nanowires and an increase in their length.
      Nanowires with diameters of about 2 nm and lengths of 8 MUm, which corresponds to
      an aspect ratio of approximately 4000, were produced. The role of oxygen is
      attributed to the enhanced oxidation of twin defects on Au nanoparticles formed
      in the first stage of the reaction. Understanding the role of oxidative etching
      is crucial to significantly increasing the yield and the length of ultrathin Au
      nanowires.

PMID- 21735496
TI  - Size dependence of the folding of multiply charged sodium cationized polylactides
      revealed by ion mobility mass spectrometry and molecular modelling.
AB  - Ion mobility spectrometry coupled with mass spectrometry was used to
      experimentally determine the three-dimensional structure of multiply charged
      sodium cationized polylactides (PLA). In particular, the experiments were
      conducted to evaluate the influence of the charge state and the size on the gas
      phase conformation of cationized PLA. The measured collision cross sections were
      then compared to calculated values obtained by computational chemistry methods.
      The most striking feature was the experimental and theoretical observation of a
      breaking point in the quasilinear relationship between the average collision
      cross sections and the number of monomer units for the triply charged cations.
      This breaking point was theoretically demonstrated, for the doubly and triply
      charged cations, to be associated with a significant folding of the polymer
      chains around the cationizing agents. The occurrence of such breaking points
      could be exploited to correlate the charge state of the most intense ion series
      observed upon electrospray ionization with the number-average molecular mass of a
      polymer.

PMID- 21735497
TI  - A highly sensitive and selective fluorescent probe for cyanide based on the
      dissolution of gold nanoparticles and its application in real samples.
AB  - We report a simple fluorescence method for detection of cyanide sensitively and
      selectively based on the dissolution of polymer-coated gold nanoparticles by
      cyanide. The lowest concentration for quantification of cyanide ions was 3.0*10(
      7) M, and other common anions nearly have no influence. Furthermore, several real
      water samples spiked with cyanide, including local groundwater, tap water, boiled
      water, and lake water, were analyzed, and the experimental results demonstrated
      that our sensing system worked well in the above water samples, with a good
      linear correlation.

PMID- 21735498
TI  - Multicomponent assembly of cavitand-based polyacylhydrazone nanocapsules.
AB  - The thermodynamically controlled syntheses of different di-, tetra-, and
      hexacavitand polyacylhydrazone nanocapsules are reported. [2+4]-, [4+8]-, and
      [6+12]-nanocapsules assemble upon reacting a tetraformyl cavitand with two
      equivalents of isophthalic dihydrazide, or terephthalic dihydrazide in the
      presence of trifluoroacetic acid, whereby the building blocks are linked together
      through 8, 16, or 24 newly formed acylhydrazone bonds. Futhermore, the reaction
      of the tetraformylcavitands with different trigonal planar trihydrazides,
      simultaneously leads to the formation of [2+4]- and [6+8]-nanocapsules in varying
      ratios that depend on the cavitand to trihydrazide ratio and the nature of the
      cavitand and trihydrazide building blocks. The product ratios are rationalized
      with the different conformational strain of the acylhydrazone linkages in these
      nanocapsules. Diffusion NMR experiments with the hexacavitand polyacylhydrazone
      nanocapsules yield solvodynamic radii that range from 1.6 to 2.5 nm, consistent
      with estimates from force field calculations, and support, that these capsules
      have solvent filled, spherical interiors, the sizes of which approaches those of
      smaller proteins.

PMID- 21735499
TI  - Controlled synthesis of monodisperse sub-100 nm hollow SnO2 nanospheres: a
      template- and surfactant-free solution-phase route, the growth mechanism, optical
      properties, and application as a photocatalyst.
AB  - Controlled synthesis of low-dimensional materials, such as nanoparticles,
      nanorods, and hollow nanospheres, is vitally important for achieving desired
      properties and fabricating functional devices. We report a systematic
      investigation of the growth of low-dimensional sub-100 nm SnO(2) hollow
      nanostructures by a mild template- and surfactant-free hydrothermal route, aiming
      to achieve precise control of morphology and size. The starting materials are
      potassium stannate and urea in an ethylene glycol (EG)/H(2)O system. We found the
      size of the SnO(2) hollow nanospheres can be controlled by simply adjusting the
      urea concentration. Investigation of the mechanism of formation of the SnO(2)
      hollow nanospheres revealed that reaction time, urea concentration, and reaction
      temperature make significant contributions to the growth of hollow nanospheres.
      On switching the solvent from EG/H(2)O to H(2)O or ethanol, the SnO(2)
      nanostructures changed from nanospheres to ultrafine nanorods and nanoparticles.
      On the basis of reaction parameter dependent experiments, oriented self-assembly
      and subsequent evacuation through Ostwald ripening are proposed to explain the
      formation of hollow nanostructures. Their size-dependent optical properties,
      including UV/Vis absorption spectra and room-temperature fluorescence spectra,
      were also studied. Moreover, the studies on the photocatalytic property
      demonstrate that the fabricated hollow structures have slightly enhanced
      photocatalytic degradation activity for rhodamine B when exposed to mercury light
      irradiation compared to solid SnO(2) nanospheres under the same conditions. The
      synthesized tin oxide nanoparticles display high photocatalytic efficiency and
      have potential applications for cleaning polluted water in the textile industry.

PMID- 21735500
TI  - One-pot functionalization of graphene with porphyrin through cycloaddition
      reactions.
AB  - Two types of graphene-based hybrid materials, graphene-TPP
      (TPP=tetraphenylporphyrin) and graphene-PdTPP (PdTPP=palladium
      tetraphenylporphyrin), were prepared directly from pristine graphene through one
      pot cycloaddition reactions. The hybrid materials were characterized by
      thermogravimetric analysis (TGA), by TEM, by UV/Vis, FTIR, Raman, and
      luminescence spectroscopy, and by fluorescence/phosphorescence lifetime
      measurements. The presence of the covalent linkages between graphene and
      porphyrin was confirmed by FTIR and Raman spectroscopy and further supported by
      control experiments. The presence of TPP (or PdTPP) in the hybrid material was
      demonstrated by UV/Vis spectroscopy, with TGA results indicating that the
      graphene-TPP and graphene-PdTPP hybrid materials contained approximately 18 % TPP
      and 20 % PdTPP. The quenching of fluorescence (or phosphorescence) and reduced
      lifetimes suggest excited state energy/electron transfer between graphene and the
      covalently attached TPP (or PdTPP) molecules.

PMID- 21735501
TI  - Fe-catalyzed thioesterification of carboxylic esters.
AB  - Second nature: Starting from shelf-stable aryl esters and thiols, a variety of
      carboxylic acid esters were transformed into the corresponding thioesters with no
      racemization of labile stereocenters. The method was successfully applied in a
      native chemical-ligation-type peptide formation, which suggests that the thiol
      may act as a co-catalyst for future 1,2-additions of pronucleophiles to
      carboxylic esters.

PMID- 21735502
TI  - Highly active organocatalysts for asymmetric anti-Mannich reactions.
AB  - Lighten the load! A family of enantiopure 4-oxy-substituted 3-aminopyrrolidines
      arising from the enantioselective ring-opening of meso-3-pyrroline oxide have
      been developed as catalysts for the asymmetric, anti-selective Mannich reaction
      (see scheme; PMP=p-methoxyphenyl; PG=protecting group). Very high catalytic
      activity (down to 0.01 mol % loading) and stereoselectivity have been recorded.

PMID- 21735503
TI  - Antimicrobial potential of Australian macrofungi extracts against foodborne and
      other pathogens.
AB  - Basidiomycetous macrofungi have therapeutic potential due to antimicrobial
      activity but little information is available for Australian macrofungi.
      Therefore, the present study investigated 12 Australian basidiomycetous
      macrofungi, previously shown to have promising activity against Staphylococcus
      aureus and Escherichia coli, for their antimicrobial potential against a range of
      other clinically relevant micro-organisms. Fruiting bodies were collected from
      across Queensland, Australia, freeze-dried and sequentially extracted with water
      and ethanol. The crude extracts were tested at 10 mg/mL and 1 mg/mL against six
      pathogens including two Gram-positive and two Gram-negative bacteria along with
      two fungi using a high throughput 96-well microplate bioassay. A degree of
      specificity in activity was exhibited by the water extract of Ramaria sp.
      (Gomphaceae) and the ethanol extracts of Psathyrella sp. (Psathyrellaceae) and
      Hohenbuehelia sp., which inhibited the growth of the two fungal pathogens used in
      the assay. Similarly, the ethanol extract of Fomitopsis lilacinogilva
      (Fomitopsidaceae) was active against the Gram-positive bacteria B. cereus only.
      Activity against a wider range of the microorganisms used in the assay was
      exhibited by the ethanol extract of Ramaria sp. and the water extract of
      Hohenbuehelia sp. (Pleurotaceae). These macrofungi can serve as new sources for
      the discovery and development of much needed new antimicrobials.

PMID- 21735504
TI  - Investigation of preparation techniques for delta2H analysis of keratin materials
      and a proposed analytical protocol.
AB  - Accurate hydrogen isotopic measurements of keratin materials have been a
      challenge due to exchangeable hydrogen in the sample matrix and the paucity of
      appropriate isotopic reference materials for calibration. We found that the most
      reproducible delta(2)H(VSMOW-SLAP) and mole fraction of exchangeable hydrogen,
      x(H)(ex), of keratin materials were measured with equilibration at ambient
      temperature using two desiccators and two different equilibration waters with two
      sets of the keratin materials for 6 days. Following equilibration, drying the
      keratin materials in a vacuum oven for 4 days at 60  degrees C was most critical.
      The delta(2)H analysis protocol also includes interspersing isotopic reference
      waters in silver tubes among samples in the carousel of a thermal conversion
      elemental analyzer (TC/EA) reduction unit. Using this analytical protocol,
      delta(2)H(VSMOW-SLAP) values of the non-exchangeable fractions of USGS42 and
      USGS43 human-hair isotopic reference materials were determined to be -78.5 +/-
      2.3 0/00 and -50.3 +/- 2.8 0/00, respectively. The measured x(H)(ex) values of
      keratin materials analyzed with steam equilibration and N(2) drying were
      substantially higher than those previously published, and dry N(2) purging was
      unable to remove absorbed moisture completely, even with overnight purging. The
      delta(2)H values of keratin materials measured with steam equilibration were
      about 10 0/00 lower than values determined with equilibration in desiccators at
      ambient temperatures when on-line evacuation was used to dry samples. With steam
      equilibrations the x(H)(ex) of commercial keratin powder was as high as 28%.
      Using human-hair isotopic reference materials to calibrate other keratin
      materials, such as hoof or horn, can introduce bias in delta(2)H measurements
      because the amount of absorbed water and the x(H)(ex) values may differ from
      those of unknown samples. Correct delta(2)H(VSMOW-SLAP) values of the non
      exchangeable fractions of unknown human-hair samples can be determined with
      atmospheric moisture equilibration by normalizing with USGS42 and USGS43 human
      hair reference materials when all materials have the same powder size.

PMID- 21735505
TI  - Measuring long-chain acyl-coenzyme A concentrations and enrichment using liquid
      chromatography/tandem mass spectrometry with selected reaction monitoring.
AB  - Long-chain acyl-coenzymes A (acyl-CoAs) (LCACoA) are the activated forms of long
      chain fatty acids and serve as key lipid metabolites. Excess accumulation of
      intracellular LCACoA, diacylglycerols (DAGs) and ceramides may create insulin
      resistance with respect to glucose metabolism. We present a new method to measure
      LCACoA concentrations and isotopic enrichment of palmitoyl-CoA ([U-(13) C]16-CoA)
      and oleoyl-CoA ([U-(13) C]18:1-CoA) using ultra-performance liquid
      chromatography/tandem mass spectrometry (UPLC/MS/MS) to quantitate seven
      different LCACoA (C14-CoA, C16-CoA, C16:1-CoA, C18-CoA, C18:1-CoA, C18:2-CoA, C20
      CoA). The molecules are separated on a reversed-phase UPLC column using a binary
      gradient with ammonium hydroxide (NH(4) OH) in water and NH(4) OH in acetonitrile
      (ACN). The LCACoA are quantified using selected reaction monitoring (SRM) on a
      triple quadrupole mass spectrometer in positive electrospray ionization (ESI)
      mode. All LCACoA ions except enriched palmitate enrichment of palmitoyl-CoA ([U(
      13)C]16-CoA) and oleoyl-CoA ([U(-13)C]18:1-CoA) using ultra-performance liquid
      chromatography/mass spectrometry (UPLC/MS/MS) to quantitate seven different
      LCACoA (C14-CoA, C16-CoA, C16:1-CoA, C18-CoA, C18:1-CoA, C18:2-CoA, C20-CoA). The
      molecules are separated on a reversed-phase UPLC column using a binary gradient
      with ammonium hydroxide (NH(4) OH) in water and NH(4) OH in acetonitrile. The
      LCACoA are quantified using selected reaction monitoring (SRM) on a triple
      quadrupolemass spectrometer in positive electrospray ionization (ESI) mode. All
      LCACoA ions except enriched palmitate and oleate were monitored as [M+2+H](+) and
      [U(13)C]16-CoA and [U(13)C]18:1-CoA were monitored as [M+16+H](+) and
      [M+18+H](+), respectively. The method is simple, sensitive and efficient (run
      time as short as 5 min) and allowed us to measure the concentration and detect
      enrichment in intramyocellular [U(13) C]16-CoA and [U(13) C]18:1-CoA during a low
      dose intravenous infusion of [U(13) C]palmitate and [U(13) C]oleate in adults
      undergoing either a saline control experiment or an insulin/glucose infusion
      experiment. This technique should allow investigators to measure the trafficking
      of extracellular fatty acids to the intracellular LCACoA pool.

PMID- 21735506
TI  - Characterisation of polyacetylenes isolated from carrot (Daucus carota) extracts
      by negative ion tandem mass spectrometry.
AB  - The potential use of negative electrospray ionisation mass spectrometry (ESI-MS)
      in the characterisation of the three polyacetylenes common in carrots (Daucus
      carota) has been assessed. The MS scans have demonstrated that the polyacetylenes
      undergo a modest degree of in-source decomposition in the negative ionisation
      mode while the positive ionisation mode has shown predominantly sodiated ions and
      no [M+H](+) ions. Tandem mass spectrometric (MS/MS) studies have shown that the
      polyacetylenes follow two distinct fragmentation pathways: one that involves
      cleavage of the C3-C4 bond and the other with cleavage of the C7-C8 bond. The
      cleavage of the C7-C8 bond generated product ions m/z 105.0 for falcarinol, m/z
      105/107.0 for falcarindiol, m/z 147.0/149.1 for falcarindiol-3-acetate. In
      addition to these product ions, the transitions m/z 243.2 -> 187.1 (falcarinol),
      m/z 259.2 -> 203.1 (falcarindiol), m/z 301.2 -> 255.2/203.1 (falcarindiol-3
      acetate), mostly from the C3-C4 bond cleavage, can form the basis of multiple
      reaction monitoring (MRM)-quantitative methods which are poorly represented in
      the literature. The 'MS(3) ' experimental data confirmed a less pronounced
      homolytic cleavage site between the C11-C12 bond in the falcarinol-type
      polacetylenes. The optimised liquid chromatography (LC)/MS conditions have
      achieved a baseline chromatographic separation of the three polyacetylenes
      investigated within 40 min total run-time.

PMID- 21735507
TI  - Validity and reliability of perinatal biomarkers of adiposity after storage as
      dried blood spots on paper.
AB  - OBJECTIVE: To validate use of chip-based immunoaffinity capillary electrophoresis
      on dried blood spot samples (DBSS) to measure obesity-related hormones. METHODS:
      Chip-based immunoaffinity capillary electrophoresis was used to measure
      adiponectin, leptin and insulin in capillary serum and DBSS in pregnant women and
      infant heelstick at birth and six weeks. Concordance of measurements was
      determined with Pearson's correlation and Bland-Altman plots. RESULTS: We report
      high concordance between results obtained from serum and DBSS. CONCLUSIONS: Ease
      of sample collection and storage makes DBSS an optimal method for use in studies
      involving neonates and young children, as well as studies conducted in areas
      where freezer storage is not available.

PMID- 21735508
TI  - Pharmacovigilance for antiretroviral drugs in Africa: lessons from a study in
      Abidjan, Cote d'Ivoire.
AB  - BACKGROUND: Although antiretroviral treatment (ART)-related adverse drug
      reactions (ADR) are documented in industrialised countries, there is no pre
      existing surveillance system dedicated to ADR monitoring in most African
      countries. We assessed knowledge towards pharmacovigilance among ART prescribers
      and available capacity of HIV clinics to conduct ADR monitoring in Abidjan, Cote
      d'Ivoire. METHODS: A questionnaire was administered to ART prescribers to assess
      their knowledge towards the occurrence of ADRs. A retrospective ADR survey was
      also conducted based on a data query of treatment modification/interruptions in
      three HIV clinics. Clinical monitors went back to medical charts to review and
      validate the reasons of the treatment modification/interruptions. RESULTS: Of the
      81 ART prescribers interviewed, 25 (31%) declared not grading ADRs and 12 (14.8%)
      declared notifying ADRs to the national regulatory authorities. Among 5252 adult
      ART-treated patients who attended the participating clinics in 2008, 599
      treatment modifications were identified. Reasons for treatment
      modification/interruptions identified in the electronic database were documented
      in the medical charts in 554 cases (92.5%), ADR accounting for 273 cases (45.5%).
      Toxicity related to ART was graded in only 58 cases (21%) in the medical charts.
      DISCUSSION: This study describes challenges limiting the implementation of
      reliable pharmacovigilance activities in HIV clinics in Cote d'Ivoire. The lack
      of knowledge of ART prescribers concerning ADR grading does not support the
      spontaneous reporting of ADRs. Using treatment modification/interruptions for ADR
      monitoring appears feasible, but improvements are needed to respond to key
      questions related to drug toxicities in the context of ART scale-up in Africa.

PMID- 21735509
TI  - The association of vitamin D use with hypercalcemia and hyperphosphatemia in
      hemodialysis patients: a case-crossover study.
AB  - PURPOSE: Elevated levels of phosphorus (P) and calcium (Ca) have been shown in
      observational studies to be associated with an increased risk of adverse clinical
      outcomes including mortality. Vitamin D sterols have been shown to increase the
      risk of hypercalcemia and hyperphosphatemia in clinical trials. We sought to
      explore these risks in real-world clinical practice. METHODS: We employed a case
      crossover design, which eliminates confounding by non-time-varying patient
      characteristics by comparing, within each patient, vitamin D doses before the
      event with those at an earlier period. Using this method, we estimated the risk
      of hypercalcemic (Ca >= 11 g/dL) and hyperphosphatemic (P >= 8 g/dL) events for
      patients at different dose quartiles of vitamin D relative to patients not on a
      vitamin D sterol. RESULTS: There was a dose-dependent association between vitamin
      D dose quartile and risk of hypercalcemia or hyperphosphatemia. In adjusted
      analyses, each increase in vitamin D quartile was associated with a multiple of
      hypercalcemia risk between 1.7 and 19 times compared with those not on vitamin D
      and a multiple of hyperphosphatemia risk between 1.8 and 4. CONCLUSION: Use of
      vitamin D sterols is associated with an increased risk of hypercalcemic and
      hyperphosphatemic events in real-world clinical practice. Other potential
      predictors of these events, such as phosphate binder use and dialysate Ca levels,
      were not examined in this analysis.

PMID- 21735510
TI  - Terahertz time-domain spectroscopy of gases, liquids, and solids.
AB  - The techniques and methods employed in the spectroscopic characterization of
      gases, liquids, and solids in the terahertz frequency range are reviewed.
      Terahertz time-domain spectroscopy is applied to address a broadband frequency
      range between 100 GHz and 5 THz with a sub-10 GHz frequency resolution. The
      unique spectral absorption features measured can be efficiently used in material
      identification and sensing. Possibilities and limitations of fundamental and
      industrial applications are discussed.

PMID- 21735511
TI  - A DFT investigation of surface-enhanced Raman scattering of adenine and 2'
      deoxyadenosine 5'-monophosphate on Ag20 nanoclusters.
AB  - We present a detailed analysis of the surface-enhanced Raman scattering (SERS) of
      adenine and 2'-deoxyadenosine 5'-monophosphate (dAMP) adsorbed on an Ag(20)
      cluster by using density functional theory. Calculated Raman spectra show that
      spectral features of all complexes depend greatly on adsorption sites of adenine
      and dAMP. The complexes consisting of adenine adsorbed on the Ag(20) cluster
      through N3 reproduce the measured SERS spectra in silver colloids, and thus
      demonstrated that adenine interacts with the silver surface via N3. We also
      investigate the SERS spectrum of adenine at the junction between two Ag(20)
      clusters and demonstrate that adenine can bind to the clusters through N3 and the
      external amino group, while dAMP can be adsorbed on the cluster in an end-on
      orientation with the ribose and phosphate groups near to or away from the silver
      cluster. In contrast to the adenine-Ag(20) complexes, the dAMP-Ag(20) complexes
      produce new and strong bands in the low- or high-wavenumber region of the Raman
      spectra, due to vibrations of the ribose and phosphate groups. Furthermore, the
      spectrum of dAMP bound to the Ag(20) cluster via N7 approaches the experimental
      SERS spectra on silver colloids.

PMID- 21735512
TI  - Sub-diffraction imaging of huntingtin protein aggregates by fluorescence blink
      microscopy and atomic force microscopy.

PMID- 21735513
TI  - Pushing wrist access to the limit: homolateral right ulnar artery approach for
      primary percutaneous coronary intervention after right radial failure due to
      radial loop.
AB  - A 67-year-old man underwent primary percutaneous coronary intervention for acute
      anterior ST elevation myocardial infarction. The right radial artery was the
      access of choice. After easy cannulation, a 360-degree loop was found at the
      elbow level. The brachial artery and a large ulnar artery were visible by
      injecting contrast through the radial loop. After an unsuccessful attempt to
      engage the loop, the operator switched entry site for the homolateral ulnar
      artery. Leaving the radial sheath in place, the cannulation of the ulnar artery
      was successful and uncomplicated. The operator could easily perform a successful
      intervention of the culprit vessel. An angiogram of the wrist, via the ulnar
      sheath showed the presence of a big interosseous artery with flow up to the hand
      and no flow in the radial and ulnar arteries distal to the sheaths. The ulnar and
      radial arteries were successfully sealed after a few hours, a valid pulsation was
      present on both arteries and no signs of ischemia were evident in the right hand
      the day after.

PMID- 21735514
TI  - Outcomes of concomitant percutaneous coronary intervention and balloon aortic
      valvuloplasty.
AB  - BACKGROUND: Coronary artery disease often coexists with severe aortic stenosis.
      The feasibility and safety of combined balloon aortic valvuloplasty (BAV) and
      percutaneous coronary intervention (PCI) are unknown. AIM: To compare outcomes
      and complications of combined BAV and PCI with BAV alone. METHODS: The study
      cohort consisted of 409 patients with severe aortic stenosis undergoing BAV from
      1/2007 to 12/2010. Overall, 329 patients underwent BAV alone and 80 underwent
      concomitant PCI. Clinical and hemodynamic data, as well as acute and intermediate
      term outcomes, were collected. RESULTS: At the operator's discretion PCI was done
      before BAV in 66 (82.5%) and after in 14 (17.5%). Patients who underwent
      concomitant procedures had a higher incidence of prior stroke and a lower
      incidence of atrial fibrillation. Procedure time and fluoroscopic time were
      significantly greater in the BAV/PCI group, (90.0 +/- 36.6 vs. 72.8 +/- 39.8, P =
      0.002 and 20.5 +/- 10.9 vs. 12.9 +/- 7.0, P < 0.001). Significantly more
      radiographic contrast was used in the BAV/PCI group (95.1 +/- 45.5 vs. 36.7 +/-
      38.4 cm(3) , P < 0.001. Serious adverse events occurred with equal frequency 13.7
      and 17.3%, P = 0.44). Transfusion requirement was also similar (21.2% vs. 20.0%,
      P = 0.81). The frequency of a periprocedural increase in troponin or creatinine
      was also similar. In the BAV alone group the mortality rate was 48.6% (n = 160)
      during a mean follow-up of 191 days, and in the BAV/PCI group the mortality rate
      was 40% (n = 32) during mean follow-up of 175.5 day, P = 0.34. CONCLUSION:
      Combined BAV and PCI are safe and are associated with similar complications as
      BAV alone and may offer protection against myocardial ischemia during BAV.

PMID- 21735515
TI  - Outcomes of small coronary artery stenting with bare-metal stents versus drug
      eluting stents: results from the NHLBI Dynamic Registry.
AB  - OBJECTIVES: Examine 1-year outcomes of patients with small coronary arteries in
      the National Heart, Lung, and Blood Institute Dynamic Registry (NHLBI) undergoing
      drug-eluting stent (DES) vs. bare-metal stent (BMS) placement. BACKGROUND: While
      randomized trials of DES vs. BMS demonstrate reduced target vessel
      revascularization, it is unclear whether similar outcomes are seen in unselected
      patients after percutaneous coronary intervention (PCI) for small coronary
      arteries. METHODS: Utilizing patients from the NHLBI Registry Waves 1-3 for BMS
      (1997-2002) and Waves 4-5 for DES (2004 and 2006), demographic, angiographic, in
      hospital, and 1-year outcome data of patients with small coronary arteries
      treated with BMS (n = 686) vs. DES (n = 669) were evaluated. Small coronary
      artery was defined as 2.50-3.00 mm in diameter. RESULTS: Compared to BMS-treated
      patients, the mean lesion length of treated lesions was longer in the DES treated
      group (16.7 vs. 13.1 mm, P < 0.001) and the mean reference vessel size of
      attempted lesions was smaller (2.6 vs. 2.7 mm, P < 0.001). Adjusted analyses of 1
      year outcomes revealed that DES patients were at lower risk to undergo coronary
      artery bypass graft surgery (Hazard Ratio [HR] 0.40, 95% confidence interval [CI]
      0.17-0.95, P = 0.04), repeat PCI (HR 0.53, 95% CI 0.35-0.82, P = 0.004), and
      experience the combined major adverse cardiovascular event rate (HR 0.59, 95% CI
      0.42-0.83, P = 0.002). There was no difference in the risk of death and
      myocardial infarction (MI) (HR 0.78, 95% CI 0.46-1.35, P = 0.38). CONCLUSIONS: In
      this real-world registry, patients with small coronary arteries treated with DES
      had significantly lower rates of repeat revascularization and major adverse
      cardiovascular events at 1 year compared to patients treated with BMS, with no
      increase in the risk of death and MI. These data confirm the efficacy and safety
      of DES over BMS in the treatment of small coronary arteries in routine clinical
      practice.

PMID- 21735516
TI  - Coil embolization for distal left main aneurysm: a new approach to coronary
      artery aneurysm treatment.
AB  - Coronary artery aneurysm is an uncommon disease, whose natural history and
      therapeutic approach are still controversial: medical therapy, surgical
      revascularization with or without aneurysm ligation or excision, and endovascular
      exclusion with membrane covered stents are all accepted and viable options,
      according to anatomic characteristics. Intracranial aneurysms are adequately
      treated by means of coil embolization, an option that, to our knowledge, has
      never been tested in coronary interventions. We report the first case of a
      coronary aneurysm involving the distal left main and the proximal left anterior
      descending artery treated with "stent-assisted" coil embolization.

PMID- 21735517
TI  - Outcomes of cardiac catheterization and percutaneous coronary intervention for in
      hospital ventricular tachycardia or fibrillation cardiac arrest.
AB  - OBJECTIVE: This study examined outcomes of patients with sudden cardiac death
      attributable to primary ventricular tachycardia (VT) or ventricular fibrillation
      (VF) that underwent cardiac catheterization with or without percutaneous coronary
      intervention (PCI). BACKGROUND: The decision to perform cardiac catheterization
      and PCI in resuscitated patients with sudden cardiac death remains controversial.
      Prior data suggest a potential benefit from percutaneous revascularization.
      METHODS: All patients with an in-hospital pulseless VT or VF cardiac arrest from
      August 2002 to February 2008 who underwent cardiac catheterization were included.
      Retrospective chart review was performed to obtain clinical, neurologic, and
      angiographic data. Primary endpoints were all-cause mortality and neurologic
      outcome. RESULTS: Two thousand and thirty-four patients had in-hospital cardiac
      arrest, of these 116 had pulseless VT or VF and were resuscitated and 93 (80%)
      underwent coronary angiography. The median time to follow-up was 1.3 years (IQR:
      0.5-2.9 years). Obstructive coronary artery disease (CAD) was observed in 74
      (79%) individuals, of whom 37 underwent PCI. Thirty-five patients with
      obstructive CAD (47%) died compared to 41% with nonobstructive CAD. In unadjusted
      and multivariable adjusted analysis PCI was not associated with lower mortality
      (adjusted hazard ratio: 1.54, 95% CI, 0.79-3.02, P = 0.20). No significant
      differences were noted in neurologic status at discharge (P = 0.49). CONCLUSION:
      In this study, an aggressive revascularization strategy with PCI did not confer a
      survival advantage nor was it associated with improved neurologic outcomes. There
      was no suggestion of harm with PCI and further studies are necessary to identify
      potential subgroups that may benefit from revascularization.

PMID- 21735518
TI  - Middle aortic syndrome with renal involvement: a staged strategy to manage
      systemic hypertension.
AB  - Long segment narrowing of the thoracoabdominal aorta or so-called middle aortic
      syndrome (MAS), is an uncommon lesion presenting variably with physical signs of
      coarctation of the aorta, hypertension, renal insufficiency and or mesenteric
      ischemia. The etiologies are multiple, but Takayasu's arteritis is a leading
      cause. Variable involvement of diverse systemic arterial systems requires
      individualized management strategies. We report a case of a successful treatment
      algorithm for severe MAS using a strategy of percutaneous aortic endovascular
      stent implantation to rebuild the distal aorta and renal auto-implantation to
      address systemic hypertension.

PMID- 21735519
TI  - First-in-man transcatheter aortic valve implantation of a 20-mm Edwards SAPIEN XT
      valve: one step forward for the treatment of patients with severe aortic stenosis
      and small aortic annulus.
AB  - We present the case of an 85-year-old woman diagnosed with severe aortic
      stenosis, porcelain aorta, and a small aortic annulus (17.3 mm), who underwent
      successful transfemoral transcatheter aortic valve implantation (TAVI) with a 20
      mm Edwards SAPIEN XT valve using the NovaFlex+ delivery system. At 1-month follow
      up the patient was in NYHA functional class I, and Doppler echocardiography
      showed a mean residual gradient of 15 mm Hg and trivial paravalvular aortic
      regurgitation. This case, which shows for the first time the feasibility of TAVI
      with a 20-mm valve, opens a new avenue for the challenging treatment of patients
      with aortic stenosis and a small aortic annulus.

PMID- 21735520
TI  - Impact of renal insufficiency on safety and efficacy of drug-eluting stents
      compared to bare-metal stents at 6 years.
AB  - BACKGROUND: There is few information on the long-term efficacy and safety of
      sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) compared to
      bare metal stents (BMS) in all-comer percutaneous coronary intervention (PCI)
      patients complicated by renal insufficiency (RI). OBJECTIVE: Our aim was to
      assess the 6-year clinical outcome of PCI-patients with RI treated exclusively
      with BMS, SES, or PES in our academic hospital. METHODS: A total of 1382
      patients, included in three cohorts of consecutive PCI-patients (BMS = 392; SES =
      498; PES = 492), were categorized by creatinine clearance calculated by the
      Cockroft-Gault formula (normal kidney function >= 90; mild RI = 60-89; moderate
      RI < 60) and systematically followed for the occurrence of major adverse cardiac
      events (MACE). RESULTS: Mortality rates were significantly higher for patients
      with moderate RI compared to mild RI and normal kidney function at 6 years
      (Kaplan-Meier estimate: moderate RI (34%) vs. mild RI (12%), P < 0.001; moderate
      RI (34%) vs. normal kidney function (8%), P < 0.001). After multivariate Cox
      regression analysis, SES and PES decreased the occurrence of target-vessel
      revascularization (TVR) and MACE at 6 years in patients with a normal creatinine
      clearance compared to BMS [adjusted hazard ratio (aHR) = 0.48, 95% CI: 0.28-0.84;
      aHR = 0.75, 95% CI: 0.57-0.97, respectively] with no significant effect on
      mortality. Safety- and efficacy end points were comparable for the three stent
      types in patients with mild- and moderate renal function. CONCLUSION: Patients
      with a normal creatinine clearance had significant improvement in TVR and MACE
      rates after SES- or PES implantation compared to BMS at 6 years. However, there
      was no superiority of both drug-eluting stents over BMS in safety and efficacy
      end points for patients with impaired renal function.

PMID- 21735521
TI  - Retroperitoneal hemorrhage after percutaneous coronary intervention in the
      current practice era: clinical outcomes and prognostic value of abdominal/pelvic
      computed tomography.
AB  - BACKGROUND: Retroperitoneal hemorrhage (RPH) is a serious but infrequent
      complication of percutaneous coronary intervention (PCI). This study aimed to
      describe the clinical outcomes of patients who developed RPH following PCI in the
      current practice era, with particular focus on treatment strategies and the
      related prognostic value of abdominal/pelvic computed tomography (CT). METHODS:
      Among 20,904 patients undergoing PCI, we identified 93 RPH (0.45%) confirmed by
      CT or by unequivocal surgical findings. We identified three groups with RPH for
      comparison: patients who developed refractory shock (systolic blood pressure <80
      mm Hg for >=30 min despite fluids and vasopressors, n = 16 [17.2%]); patients
      with transient hypotension (<30 min, n = 34 [36.6%]); and patients without
      hypotension (n = 43 [46.2%]). The primary endpoint was a composite of in-hospital
      mortality, myocardial infarction, and cerebral vascular accident (CVA). RESULTS:
      Baseline clinical, angiographic, and procedural characteristics were similar
      among the three groups. Patients who developed refractory shock had significantly
      more bleeding quantified by abdominal/pelvic CT (P < 0.001), had a higher rate
      and amount of red blood cell transfusion (P < 0.001), and were managed invasively
      more frequently (68.7%) than the rest of the population. The primary endpoint
      trended higher in patients presenting with refractory shock; however, this
      difference was not statistically significant. The volume of bleeding quantified
      by CT and the timing of imaging diagnosis did not correlate with the primary
      endpoint. Red blood cell transfusion, but not clopidogrel discontinuation, was
      associated with the primary endpoint. CONCLUSIONS: RPH remains as a serious
      complication of PCI and is associated with high rates of mortality and morbidity
      independently of the therapeutic strategy. In patients who were hemodynamically
      stable, RPH volume as quantified by non-contrast abdominal/pelvic CT did not
      contribute to prognosis.

PMID- 21735522
TI  - A novel mother and child technique with a 4F inner catheter based on proper
      alignment of both catheters.
AB  - We occasionally encounter difficult cases of stent and balloon delivery to the
      distal lesion due to severe calcification or tortuosity of the proximal section.
      We describe a novel mother and child technique with a 4F inner catheter based on
      proper alignment of both catheters to deliver balloon, stent, and guide catheter
      to the distal lesion.

PMID- 21735523
TI  - Thrombus aspiration alone during primary percutanous coronary intervention as
      definitive treatment in acute ST-elevation myocardial infarction.
AB  - BACKGROUND: In some patients with ST-segment elevation myocardial infarction
      (STEMI) who underwent primary percutanous coronary intervention (pPCI) with
      thrombus aspiration, residual stenosis after thrombus aspiration is non
      significant and additional balloon dilatation or stent placement may be
      unnecessary. We investigated the angiographic, procedural, and clinical outcomes
      of these patients in our single center pPCI-database. In addition, to gain
      insight in the pathological mechanisms of coronary thrombosis in these patients,
      we established the histopathological characteristics and age of the aspirated
      material. METHODS: This study consists of STEMI patients who underwent pPCI with
      thrombus aspiration alone in our institution. Thrombus material was collected and
      processed and the sections were analyzed for the presence of fresh (<1 day) or
      older thrombus (>1 day) and plaque components. One year clinical follow-up was
      obtained and vital status was assessed up to March 2010. RESULTS: We identified
      16 STEMI patients who underwent thrombus aspiration alone as the definitive
      treatment during pPCI. Acceptable flow with minimal non-significant residual
      stenosis immediately after thrombus aspiration was present in 14 patients (88%).
      In four patients (25%) repeat angiography was performed after several days and
      disappearance of the residual thrombus could be confirmed in three patients.
      During follow-up, repeat target lesion revascularization was performed in one
      patient at 53 days. No recurrent myocardial infarction was observed. Two patients
      died 1,166 and 1,228 days after the index-event from non-cardiac causes.
      CONCLUSIONS: In selected STEMI patients undergoing pPCI, thrombus aspiration
      alone is feasible and safe on the short-term and there appears to be no high risk
      of recurrent ischemic events during follow-up. Our results suggest that
      additional balloon inflation or stent implantation may be unnecessary in selected
      patients, when there is no significant residual stenosis after thrombus
      aspiration.

PMID- 21735524
TI  - Incomplete arterial healing 8 years after the implantation of sirolimus-eluting
      stent. In vivo visualization by optical coherence tomography.
AB  - The time course of complete arterial healing after drug eluting stent
      implantation is unknown. We present a case of incomplete endothelialization and
      late stent malapposition identified by optical coherence tomography 8 years after
      a sirolimus-eluting stent implantation, which was not related with any adverse
      clinical event.

PMID- 21735525
TI  - Pseudoaneurysm after transradial cardiac catheterization: case series and review
      of the literature.
AB  - INTRODUCTION: Radial artery access for diagnostic and therapeutic procedures
      offers clear advantages in terms of vascular complications. While radial artery
      occlusion may occasionally complicate radial artery access, new methods of
      hemostasis are now utilized to avoid this complication. In contrast,
      pseudoaneurysm following radial artery access is an extremely uncommon
      complication. METHODS: We describe a series of patients who developed radial
      artery pseudoaneurysm after their procedure. RESULTS: Five patients developed
      radial pseudoaneurysm after diagnostic and interventional procedures, likely
      reflecting inadequate hemostasis following the procedure and delayed bleeding
      complicating systemic anticoagulation. CONCLUSIONS: While uncommon, radial artery
      pseudoaneurysm may complicate cardiac catheterization procedures, with
      anticoagulation an important contributor. The clinical presentation, likely
      precipitating mechanisms and treatment options are discussed.

PMID- 21735526
TI  - Rotational angiography for preinterventional imaging in transcatheter aortic
      valve implantation.
AB  - OBJECTIVE: To evaluate the clinical value of 3D rotational angiography, as a tool
      for imaging and measuring 3D anatomy, coupled with transesophageal echocardiogram
      (TEE) as preinterventional imaging for transcatheter aortic valve implantation
      (TAVI) procedures. BACKGROUND: TAVI is a growing field in cardiology. An
      understanding of the 3D anatomy of the aortic root is crucial for patient
      selection and for the optimal planning and guidance of such procedures. Current
      techniques include 3D imaging (with MSCT MRI and 3D TEE) combined with multiplane
      TEE. Nevertheless, a gold standard of 3D imaging is yet not defined. 3D
      rotational angiography provides 3D anatomy information in the cathlab. Initially
      designed for nonmoving anatomical structures, one can adapt the protocol to
      temporarily minimize the heart anatomy motion during rotational angiography.
      METHODS: Ninety-nine consecutive patients (61 females, 38 males, age 80.9 +/- 5.2
      years) with symptomatic aortic stenosis underwent 3D rotational angiography to
      assess the anatomical suitability of potential TAVI candidates. 3D rotational
      angiography with a C-Arm (Innova 3100(IQ) , GE Healthcare, Chalfont St Giles, UK)
      was performed to create the 3D anatomy of the aortic root. Coronary angiography
      and pelvic vessel angiography were performed during the same examination.
      Measurements of the aortic annulus and the sinotubular junction were made on the
      3D cross-sections and were compared to TEE. Radiation dose to the patient was
      also monitored. RESULTS: In all 99 patients, 3D rotational angiography was
      performed successfully with good imaging of the aortic root and measurements of
      the aortic annulus. In patients scheduled for SAPIEN valve implantation, the
      distances from the annulus to the coronary ostia were also measured. Of 99
      patients, 80 subsequently underwent successful implantation. There is a good
      correlation to the TEE in the measured aortic annulus (22.13 +/- 2.09 mm in
      rotational angio, 21.58 +/- 2.09 mm TEE, Spearman r = 0.88, 95% IC [0.83;0.92], P
      < 0.0001) and sinotubular junction (26.19 +/- 2.71 mm in rotational angio, 26.22
      +/- 2.73 mm TEE, Spearman r = 0.83, 95% IC [0.75;0.88], P < 0.0001). The
      effective dose is a fraction of the X-ray dose required for multi-slice computed
      tomography. CONCLUSION: Given that this technology is available in the cathlab at
      reasonable dose levels, 3D rotational angiography has proven to be a suitable
      preinterventional 3D imaging modality for TAVI procedures. Together, the raw
      angiographic data and the reconstructed 3D volume provide all the necessary
      anatomical information necessary for this procedure, including the measurements.

PMID- 21735527
TI  - Prospective evaluation of myocardial ischemia related to post-procedural side
      branch stenosis in bifurcated lesions treated by provisional approach with drug
      eluting stents.
AB  - OBJECTIVES: To prospectively assess the impact of post-procedural side-branch
      (SB) stenosis on inducible myocardial ischemia in patients with bifurcated
      lesions undergoing percutaneous interventions. BACKGROUND: Provisional-stenting
      with drug-eluting stents (DES) is the recommended strategy to treat
      percutaneously bifurcated lesions but is associated to variable degrees of
      residual SB stenosis. The role of SB residual stenosis on post-procedural
      myocardial ischemia is uncertain. METHODS: Patients with bifurcations treated by
      DES according to provisional-stenting technique were enrolled in the study if
      they had no other untreated lesion. Patients were divided into two groups
      according to post-procedural 3D-quantitative coronary analysis (3DQCA): group OR
      (optimal result: stenosis < 50% of SB lumen area at 3DQCA) and group SR,
      suboptimal result: (stenosis >= 50% of SB lumen area at 3DQCA). Treadmill
      exercise stress test (EST) was performed within 1 week from PCI. The primary
      study endpoint was myocardial ischemia (>=1 mm ST-segment depression at EST).
      RESULTS: Sixty patients were enrolled: 49 (81.7%) comprised group OR and 11
      (18.3%) group SR. Post-PCI myocardial ischemia at EST was inducible in 17 (34.7%)
      patients of group OR versus 10 (90.9%) patients of group SR (P = 0.0007). During
      the follow-up, patients of Group SR (vs. Group OR) had a significantly higher
      occurrence of inducible myocardial ischemia during late (>8 weeks) stress tests
      (P < 0.001). CONCLUSIONS: In patients with bifurcated lesions treated by a
      provisional-stenting technique, residual SB stenosis >= 50% at 3DQCA is
      associated with post-procedural inducible myocardial ischemia at EST.

PMID- 21735528
TI  - Quality improvement in the door-to-balloon times for ST-elevation myocardial
      infarction patients presenting without chest pain.
AB  - OBJECTIVE: To assess a quality improvement initiative aimed at minimizing door-to
      balloon (DTB) times for ST-elevation myocardial infarction (STEMI) patients
      presenting without chest pain. BACKGROUND: Timely percutaneous coronary
      intervention (PCI) is the cornerstone of STEMI care. The absence of chest pain
      delays PCI. Improvements in DTB times may need to focus on atypical presentation
      patients. METHODS: We compared DTB times on all STEMI patients admitted through
      the emergency department who underwent PCI before (Phase I; October 2004-June
      2007) and after (Phase II; July 2007-October 2009) the quality improvement
      effort, which mandated rapid electrocardiogram (ECG) triage for an expanded list
      of presenting symptoms. RESULTS: In Phase I (69 patient, 60 with chest pain),
      patients with chest pain had a shorter mean time to first ECG (ECG Interval) by
      32.0 min (P < 0.01) and nonsignificantly faster mean DTB time by 42.0 min (P =
      0.07) compared to patients who presented without chest pain. In Phase II (62
      patients, 56 with chest pain) compared to Phase I, mean ECG interval decreased by
      44 min (P = 0.02) and mean DTB time by 99 min (P = 0.01) in patients without
      chest pain, eliminating the differences in ECG intervals between typical and
      atypical presentations (12 min vs. 11 min, P = 0.91). Multivariable analysis
      controlling for on/off hours and patient characteristics confirmed these
      findings. CONCLUSIONS: A simple modification of emergency room ECG triage
      protocol, which expands indications for rapid ECG performance, was successful in
      improving rapid reperfusion for patients with STEMI presenting without chest
      pain.

PMID- 21735529
TI  - Transcatheter closure of an iatrogenic aorto-right ventricular fistula.
AB  - Aortocardiac fistulas are rare, especially if they develop after an aortic valve
      replacement surgery. We report the case of a 54-year-old male submitted to aortic
      valve replacement and implantation of an ascending aortic prosthetic graft,
      complaining of exertional dyspnea, who was found to have significant shunt
      between the aortic root and right ventricle (RV), and de novo moderate pulmonary
      hypertension. At the catheterization laboratory, the left-to-right shunt was
      confirmed (Qp:Qs = 1.9:1). Contrast angiography of the ascending aorta showed a
      significant flow into the right ventricular cavity, and the fistulous tract was
      then measured, inflating a Tyshak II balloon of 10 * 20 mm (NuMED, Hopkinton, New
      York), until achieving a complete interruption of flow. Minimal diameter of the
      defect was 4.9 mm. Percutaneous closure of the aorto-RV shunt was performed under
      general anesthesia and transesophageal echocardiogram and fluoroscopic guidance.
      Using a venous and an arterial femoral access, a 0.035" hydrophilic guide-wire
      crossed the defect between the aorta and RV, creating an arteriovenous loop.
      Then, using a 7F Delivery System 45 degrees  (AGA medical corporation, Golden
      Valley, MN) an Amplatzer Duct Occluder((r)) (AGA Medical Corporation) 8/6 mm was
      advanced and released within the defect, achieving an almost complete closure of
      the fistulous tract.

PMID- 21735530
TI  - Percutaneous left main coronary disease treatment without on-site surgery back-up
      in patients with acute coronary syndromes: immediate and 2-year outcomes.
AB  - BACKGROUND: Best revascularization strategy in patients with acute coronary
      syndromes (ACS) and unprotected left main (ULM) coronary disease is still debate
      reflecting lack of convincing data. OBJECTIVES: To assess clinical feasibility
      and efficacy of ULM percutaneous coronary intervention (PCI) in patients with ACS
      and describe the practice of a center without on-site surgical back-up over a 7
      year period. METHODS: Data on high-risk patients with ACSs undergoing
      percutaneous ULM treatment were prospectively collected in an independent
      registry. Primary end-points of this study were immediate and long-term outcomes
      expressed as target lesion failure (TLF, composite of cardiac death, myocardial
      infarction (MI), and target lesion revascularization). RESULTS: Between January
      2003 and January 2010, 200 consecutive patients were included in this study.
      Angiographic success was obtained in 95% of patients but procedural success was
      87% primarily affected by an 11% of in-hospital cardiac mortality. At median
      follow-up of 26 months (IQ 10-47), the overall TLF rate was 28.5%, with 16.0% of
      cardiac death, 7.0% of MI, and 10.5% of clinically driven target lesion
      revascularization rates. Cumulative definite/probable stent thrombosis was 3.5%.
      Elevated EuroSCORE value and pre-procedural hemodynamic instability were the
      strongest predictors of TLF. Temporal trend analysis showed progressive but not
      significant improvement for both immediate (P = 0.110) and long-term (P = 0.073)
      outcomes over the study period. CONCLUSIONS: This single-center study based on
      current clinical practice in patient with ULM disease and ACS confirmed PCI as
      feasible revascularization strategy in absence of on-site cardio-thoracic
      support. Nevertheless, the outcome of these high-risk patients is still hampered
      by a sensible in-hospital mortality rate.

PMID- 21735531
TI  - Reduced antiplatelet therapy after drug-eluting stenting: multicenter Janus Flex
      carbostent implantation with short dual antiplatelet treatment for 2 or 6 months
      MATRIX study.
AB  - OBJECTIVES: The Multicentre registry with Antiplatelet TReatment two-sIX months
      (MATRIX) evaluated safety and efficacy at 12-month follow-up of Janus Flex
      stenting with 2- or 6-month dual antiplatelet therapy (DAT) period. BACKGROUND:
      There are no data of Janus Flex stent (Carbostent and Implantable Devices-CID,
      Saluggia, Italy), a polymer-free, tacrolimus-eluting coronary stent, followed by
      short-term DAT, in daily practice. METHODS: Patients were prospectively enrolled
      at 12 high-volume procedures centres. After stenting, four sites prescribed 2
      month DAT, eight sites 6-month DAT. Major adverse cardiac events (MACE) and stent
      thrombosis (ST) rate was evaluated at 12-month follow-up, for entire population,
      as well as for 2- and 6-month DAT groups, distinctly. MACE included cardiac
      death, myocardial infarction (MI), and target lesion revascularization (TLR).
      RESULTS: From March 2007 to June 2008, 572 patients (mean age 64.91 +/- 11 years,
      77.45% males) were enrolled. After successful stenting, 12-month follow-up showed
      a 12.74% MACE occurrence (cardiac death 0.98%; MI 3.13%; TLR 8.62%), with good
      Janus Flex safety profile confirmed by only two (0.39%) ST. After adjustment for
      potential confounding, no significant differences were noted at 12-month follow
      up among 2- or 6-month DAT groups (MACE-8.99% versus 12.47%, P = 0.16; cardiac
      death-0.54% versus 1.14%, P = 0.52; MI-2.38% versus 2.71%, P = 0.83; TLR-5.66%
      versus 10.60%, P = 0.20; ST-0% versus 0.55%, P = 0.99). At multivariable
      analysis, DAT time duration was not an independent risk factor for adverse events
      (adjusted HR 0.47, 95% confidence interval 0.16-1.35, P = 0.16). CONCLUSIONS:
      Janus Flex coronary stenting, followed by short DAT, is safe and feasible,
      without differences between 2- and 6-month DAT groups. A randomized trial
      confirming these encouraging data is needed.

PMID- 21735532
TI  - Transcatheter aortic valve implantation when classical access routes are
      unavailable.
AB  - A 90-year-old woman with symptomatic degenerative aortic stenosis had a logistic
      Euroscore greater than 53.29%, indicating a high surgical risk. She was therefore
      advised to undergo transcatheter aortic valve implantation. Both iliac arteries
      showed subocclusive calcifications, and the left subclavian artery was narrow and
      calcified. The left common carotid (LCC) artery was chosen as the access route.
      After surgical exposure of the LCC artery, the Corevalve Revalving 29-mm
      bioprosthesis was implanted successfully. No access-site complications occurred.
      In our experience, a substantial proportion of elderly patients have vascular
      lesions precluding use of the femoral route. Brachiocephalic access routes may be
      valuable when no other options are available.

PMID- 21735533
TI  - Lack of long-term clinical benefit of thrombus aspiration during primary
      percutaneous coronary intervention with paclitaxel-eluting stents or bare-metal
      stents: post-hoc analysis of the PASSION-trial.
AB  - BACKGROUND: Although current clinical guidelines recommend the use of thrombus
      aspiration (TA) during primary percutaneous coronary intervention (PPCI),
      previous studies evaluating TA demonstrated contradictory results. The aim of
      this study was to evaluate long-term clinical outcome after TA in adjunct to PPCI
      for acute ST-segment myocardial infarction (STEMI), as compared with conventional
      treatment, with the use of paclitaxel-eluting stents or bare-metal stents.
      METHODS: We analyzed data of the PASSION trial, in which 619 patients with STEMI
      were randomly assigned to a paclitaxel-eluting stent or a bare-metal stent. TA
      was performed in 311 patients (50.2%). Clinical endpoints at 2 years were
      compared between patients who received TA during PPCI with patients who underwent
      conventional PPCI. The primary outcome of interest was a composite of cardiac
      death, recurrent myocardial infarction (MI), or target-lesion revascularization
      (TLR). A propensity score model was made to account for baseline differences that
      could have affected the probability of performing TA. RESULTS: Complete follow-up
      was available for 598 patients (96.6%). The cumulative incidence of the combined
      outcome measure of cardiac death, recurrent MI, or TLR was 40 (13.0%) in the TA
      group and 41 (13.5%) in the conventional PPCI group (HR 0.96; 95% CI 0.62-1.47; P
      = 0.84). Also after adjusting for propensity score, no significant difference in
      event rate was observed between both treatment groups. CONCLUSIONS: In this post
      hoc analysis of the PASSION trial, TA in adjunct to PPCI did not affect rates of
      major adverse cardiac events at 2 years follow-up, as compared with conventional
      PPCI.

PMID- 21735534
TI  - Treatment of a degenerative stenosed CoreValve((r))  aortic bioprosthesis by
      transcatheter valve-in-valve insertion.
AB  - BACKGROUND: Transcatheter aortic valve insertion (TAVI) is an emerging therapy in
      patients at high risk for open heart surgery. The long-term durability of the
      bioprosthesis is unknown. This is the first report of a severely degeneratively
      stenosed 2nd generation 26 mm CoreValve((r)) aortic bioprosthesis which occurred
      five and a half years after TAVI. METHODS AND RESULTS: A 92-year-old patient
      presented with decompensated heart failure NYHA class IV, pulmonary edema, and
      severe pulmonary hypertension. Echocardiography revealed critical AV-stenosis due
      to heavily calcified bioprosthetic valve leaflets. Due to high surgical risk with
      an EuroSCORE of 64.97% and a STS-mortality score of 27.0%, we decided to attempt
      a valve-in-valve insertion of a 3rd generation CoreValve((r)) prosthesis of the
      same size. Following the delicate retrograde passage of the calcified valve with
      a preformed stiff wire, balloon valvuloplasty of the severely stenosed
      CoreValve((r)) prosthesis under rapid right ventricular pacing was complicated by
      two balloon catheter ruptures. Insertion of the 3rd generation CoreValve((r))
      prosthesis of the same size was quite complex but finally it was successfully
      completed. There was mild periprosthetic regurgitation and significant decrease
      in transaortic pressure without residual transvalvular gradient immediately after
      TAVI. Echocardiography and clinical follow-up at 72 hr after TAVI confirmed
      excellent valve function with a decrease in systolic pulmonary artery pressure
      from 70 mm Hg to 35 mm Hg, increase in LV-EF from 35% to 45%, and improvement of
      functional status from NYHA IV to NYHA II. The patient was discharged in good
      medical conditions at day eight. CONCLUSION: Degenerative stenosis of a
      CoreValve((r)) bioprothesis may be observed during long-term follow-up after
      successful TAVI for the treatment of severe aortic valve stenosis. A second valve
      in-valve insertion appears feasible but may require particular interventional
      approaches.

PMID- 21735535
TI  - 3-D guidance of complex pulmonary artery stent placement using reconstructed
      rotational angiography with live overlay.
AB  - Technologies which allow rotational angiographic image acquisition and three
      dimensional (3-D) vascular reconstruction with subsequent fluoroscopic
      registration for live 3-D image overlay are rapidly being adopted. We present the
      first use of rotational angiography with integrated 3-D image overlay for
      guidance during complex pulmonary artery stent placement. Technical
      considerations, advantages, and limitations of this procedural strategy are
      discussed.

PMID- 21735536
TI  - Percutaneous treatment of a femoral artery pseudoaneurysm using the StarClose
      vascular closure system.
AB  - Formation of a femoral artery pseudoaneurysm is not infrequent after femoral
      arterial access. We successfully treated a pseudoaneurysm of the femoral artery
      using the StarClose vascular closure system. Closing device can be an alternative
      option for the treatment of pseudoaneurysm.

PMID- 21735537
TI  - Determination of trace carvedilol by solid substrate-room temperature
      phosphorimetry, based on its activating effect on hypochlorite-oxidizing amaranth
      using sodium dodecyl benzene sulphonate as sensitizer.
AB  - This work proposes a simple and sensitive solid substrate-room temperature
      phosphorimetry (SS-RTP) for the selective determination of carvedilol (CV). The
      method is based on the sensitizing effect of sodium dodecyl benzene sulphonate
      (SDBS) on CV to activate the oxidation between NaClO and amaranth, resulting in
      the intense quenching of room temperature phosphorescence (RTP) of the system.
      Compared with non-SDBS system, the reduction of phosphorescence intensity
      (DeltaI(p)) with SDBS is 16.5 times higher and is directly proportional to the
      content of CV, covering a wide range 0.080-16.00 fg/spot. The regression equation
      of the working curve can be expressed as DeltaI(p) = 0.7780 + 7.057 m(CV)
      (fg/spot) (correlation coefficient (r) = 0.9976, n = 8), with a detection limit
      (LD) of 0.020 fg/spot (corresponding concentration is 5.1 * 10(-14) g/mL, sample
      volume is 0.40 MUL/spot). This sensitive method has also been applied to
      determine trace CV in human plasma and the results agreed with synchronous
      fluorimetry (SF). The activation energy (E) and rate constant (k) of this
      activating reaction were 69.04 kJ/mol and 3.580 * 10(-4) s(-1), respectively. The
      reaction mechanism is also discussed.

PMID- 21735538
TI  - A highly selective fluorescent probe for pyrophosphate detection in aqueous
      solutions.
AB  - A novel and simple fluorescence enhancement method is introduced for selective
      pyrophosphate (PPi) sensing in an aqueous solution. The method is based on a 1:1
      metal complex formation between tris(8-hydroxyquinoline-5-sulphonate)
      thulium(III) [Tm(QS)(3)] and PPi ion. The linear response covers a concentration
      range of 1.6 * 10(-7) -1.0 * 10(-5)  mol/L PPi and the detection limit is 2.3 *
      10(-8)  mol/L. The association constant of Tm(QS)(3) -PPi complex was calculated
      as 2.6 * 10(5)  mol/L. Tm(QS)(3) shows a selective and sensitive fluorescence
      enhancement toward PPi ion in comparison with I(3)(-), NO(3)(-), CN(-), CO(3)(2
      ), Br(-), Cl(-), F(-), H(2) PO(4) (-) and SO(4)(2-), which is attributed to
      higher stability of the inorganic complex between pyrophosphate ion and
      Tm(QS)(3).

PMID- 21735539
TI  - Maternal and zygotic requirements for src64 during Drosophila cellularization.
AB  - Cellularization of the multinucleate Drosophila embryo occurs shortly after
      zygotic transcription begins. During cellular blastoderm morphogenesis, the
      microfilament cytoskeleton undergoes extensive reorganization. This cytoskeletal
      reorganization includes synchronized microfilament contraction regulated by
      src64, a gene encoding a Src nonreceptor tyrosine kinase. We report that src64 is
      maternally expressed in the Drosophila embryo and acts primarily as a maternal
      gene during cellularization. However, we show that src64 has some zygotic
      activity during late cellularization. By using compound chromosomes to generate
      embryos with wild-type levels of maternal src64 activity, we show that this
      zygotic activity is normally nonessential. We also report the identification of
      an alternate src64 transcript. Expression of this transcript is not affected by
      the src64Delta17 deletion mutation, explaining the presence of low levels of
      src64 activity observed in src64Delta17 mutants.

PMID- 21735540
TI  - Somatic gonadal cells: the supporting cast for the germline.
AB  - Cell-cell signaling and adhesion are critical for establishing tissue
      architecture during development and for maintaining tissue architecture and
      function in the adult. Defects in adhesion and signaling can result in
      mislocalization of cells, uncontrolled proliferation and improper
      differentiation, leading to tissue overgrowth, tumor formation, and cancer
      metastasis. An important example is found in the germline. Germ cells that are
      not incorporated into the gonad exhibit a greater propensity for forming germ
      cell tumors, and defects in germline development can reduce fertility. While much
      attention is given to germ cells, their development into functional gametes
      depends upon somatic gonadal cells. The study of model organisms has provided
      great insights into how somatic gonadal cells are specified, the molecular
      mechanisms that regulate gonad morphogenesis, and the role of germline-soma
      communication in the establishment and maintenance of the germline stem cell
      niche. This work will be discussed in the context of Drosophila melanogaster.

PMID- 21735541
TI  - Generation of transgenic mice overexpressing EfnB2 in endothelial cells.
AB  - Genetic studies have shown that ephrin-B2 and its cognate EphB4 receptor are
      necessary for normal embryonic angiogenesis. Moreover, there is overwhelming
      evidence that ephrin-B2 is involved in tumor vascularization, yet its role in
      adult angiogenesis has been difficult to track genetically. Here, we report the
      generation of transgenic mice that over-express EfnB2 specifically in endothelial
      cells (ECs). We show that exogenous expression of EfnB2 under the control of the
      Tie2 promoter/enhancer regions in ECs does not affect viability or growth of the
      transgenic animals. We further show that targeted expression of EfnB2 in ECs is
      not sufficient to rescue severe cardiovascular defects at mid-gestation stages
      but rescues early embryonic lethality associated with loss-of-function mutation
      in EfnB2. This mouse model will be useful to study the role of ephrin-B2 in
      physiological and pathological angiogenesis.

PMID- 21735542
TI  - Species sensitivity distribution evaluation for selenium in fish eggs:
      considerations for development of a Canadian tissue-based guideline.
AB  - A freshwater Se guideline was developed for consideration based on concentrations
      in fish eggs or ovaries, with a focus on Canadian species, following the Canadian
      Council of Ministers of the Environment protocol for developing guideline values.
      When sufficient toxicity data are available, the protocol recommends deriving
      guidelines as the 5th percentile of the species sensitivity distribution (SSD).
      When toxicity data are limited, the protocol recommends a lowest value approach,
      where the lowest toxicity threshold is divided by a safety factor (e.g., 10). On
      the basis of a comprehensive review of the current literature and an assessment
      of the data therein, there are sufficient egg and ovary Se data available for
      freshwater fish to develop an SSD. For most fish species, Se EC10 values (10%
      effect concentrations) could be derived, but for some species, only no-observed
      effect concentrations and/or lowest-observed-effect concentrations could be
      identified. The 5th percentile egg and ovary Se concentrations from the SSD were
      consistently 20 ug/g dry weight (dw) for the best-fitting distributions. In
      contrast, the lowest value approach using a safety factor of 10 would result in a
      Se egg and ovary guideline of 2 ug/g dw, which is unrealistically conservative,
      as this falls within the range of egg and ovary Se concentrations in laboratory
      control fish and fish collected from reference sites. An egg and ovary Se
      guideline of 20 ug/g dw should be considered a conservative, broadly applicable
      guideline, as no species mean toxicity thresholds lower than this value have been
      identified to date. When concentrations exceed this guideline, site-specific
      studies with local fish species, conducted using a risk-based approach, may
      result in higher egg and ovary Se toxicity thresholds.

PMID- 21735543
TI  - Including impacts of particulate emissions on marine ecosystems in life cycle
      assessment: the case of offshore oil and gas production.
AB  - Life cycle assessment is increasingly used to assess the environmental
      performance of fossil energy systems. Two of the dominant emissions of offshore
      oil and gas production to the marine environment are the discharge of produced
      water and drilling waste. Although environmental impacts of produced water are
      predominantly due to chemical stressors, a major concern regarding drilling waste
      discharge is the potential physical impact due to particles. At present, impact
      indicators for particulate emissions are not yet available in life cycle
      assessment. Here, we develop characterization factors for 2 distinct impacts of
      particulate emissions: an increased turbidity zone in the water column and
      physical burial of benthic communities. The characterization factor for turbidity
      is developed analogous to characterization factors for toxic impacts, and ranges
      from 1.4 PAF (potentially affected fraction) . m(3) /d/kg(p) (kilogram
      particulate) to 7.0 x 103 [corrected] for drilling mud particles discharged from
      the rig. The characterization factor for burial describes the volume of sediment
      that is impacted by particle deposition on the seafloor and equals 2.0 * 10(-1)
      PAF . m(3) /d/kg(p) for cutting particles. This characterization factor is
      quantified on the basis of initial deposition layer characteristics, such as
      height and surface area, the initial benthic response, and the recovery rate. We
      assessed the relevance of including particulate emissions in an impact assessment
      of offshore oil and gas production. Accordingly, the total impact on the water
      column and on the sediment was quantified based on emission data of produced
      water and drilling waste for all oil and gas fields on the Norwegian continental
      shelf in 2008. Our results show that cutting particles contribute substantially
      to the total impact of offshore oil and gas production on marine sediments, with
      a relative contribution of 55% and 31% on the regional and global scale,
      respectively. In contrast, the contribution of particulate emissions to the total
      impact on the marine water column is of minor importance. We conclude that
      particles are an important stressor in marine ecosystems, particularly for marine
      sediment, and particulate emissions should therefore be included in a (life
      cycle) impact assessment of offshore oil and gas production.

PMID- 21735544
TI  - Human mesenchymal stromal cells express CD14 cross-reactive epitopes.
AB  - Mesenchymal stromal cells (MSCs) do not express a unique definite epitope or
      marker gene. As such, minimal criteria were recently established for defining
      multipotent MSC. These criteria include expression of CD73, CD90, CD105, and a
      lack of hematopoietic marker expression. However, we detected binding of a CD14
      antibody on bone marrow- and placenta-derived MSC and investigated the staining
      of CD14 antibodies on these MSC in more detail. The MSC were isolated from human
      bone marrow and placenta tissue, expanded, characterized by quantitative RT-PCR,
      flow cytometry, and immunocytochemistry and differentiated to generate
      osteoblasts, chondrocytes, and adipocytes. The CD14-cross-reactive MSCs were
      enriched by cell sorting. Human peripheral blood mononuclear cells, fibroblasts,
      and hematopoietic cell lines served as controls. Utilizing four different clones
      of CD14 monoclonal antibodies, we found that three CD14 reagents stained the MSC.
      Two CD14 antibodies (HCD14 and M5E2) clearly marked the CD90(+) MSC population
      with distinct intensities, clone 134 620 generated a shift in flow cytometry
      histograms, but clone MPhiP9 did not stain MSC. Transcripts encoding CD14 or the
      CD14 protein were not detected in MSC. We confirm that bone marrow- and placenta
      derived MSC do not express CD14 and that the CD14 antibody MPhiP9 discriminates
      between monocytes and MSC more efficiently than the other antibodies employed
      here. This investigation does not contradict previous work but provides a more
      accurate characterization of MSC.

PMID- 21735546
TI  - In-situ observation of nucleation and growth of PbSe magic-sized nanoclusters and
      regular nanocrystals.
AB  - In-situ observation of the temporal evolution of the absorption of PbSe
      nanocrystals (NCs) via a low-temperature noninjection approach is presented.
      Based on a model reaction of lead oleate (Pb(OA)(2) ) and n-trioctylphosphine
      selenide (TOPSe) in 1-octadecene at 35-80  degrees C, the use of commercially
      available TOP (90 or 97%) in affecting the formation of the NCs is explored.
      TOPSe solutions made from TOP 90% exhibited higher reactivity than those made
      from TOP 97%. (31)P NMR spectroscopy detected no dioctylphosphine selenide
      (DOPSe) but some DOP in ~1.0 M TOPSe/TOP solution (made from TOP 90%), as well as
      no diphenylphosphine selenide (DPPSe) when DPP was added to the ~1.0 M solution.
      Hence, it is proposed that, for the formation of PbSe monomers, an indirect
      pathway dominates with the formation of a Pb-P complex/intermediate, which
      results from the activation of Pb(OA)(2) by a phosphine compound (such as DPP,
      DOP, or TOP) and in turn reacts with TOPSe. With the use of TOP 90% and the
      addition of secondary phosphine DPP, the formation of PbSe magic-sized
      nanoclusters (MSNCs) and regular NCs (RNCs) is investigated. With proper tuning
      of the synthesis conditions, the formation of various PbSe MSNCs versus RNCs is
      monitored in situ with versus without the addition of DPP, or at different
      reaction temperatures but otherwise identical synthetic formulation and reaction
      parameters. Accordingly, the degree of supersaturation (DS) of the PbSe monomer
      affecting the development of these PbSe MSNCs versus RNCs is proposed; the higher
      the DS, the more the MSNCs are favored. Also, surface-determined cluster-cluster
      aggregation is proposed to be the growth mechanism for both the RNCs and MSNCs.
      For the former, quantized growth is followed by continuous growth. For the
      latter, the sizes of the magic-sized families are calculated.

PMID- 21735545
TI  - High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating
      antibody responses.
AB  - We have developed a high-throughput platform to detect the presence of HIV-1 and
      SIV-specific ADCC-mediating antibody responses. The assay is based on the
      hydrolysis of a cell-permeable fluorogenic peptide substrate containing a
      sequence recognized by the serine protease, Granzyme B (GzB). GzB is delivered
      into target cells by cytotoxic effector cells as a result of antigen (Ag)
      specific Ab-Fcgamma receptor interactions. Within the target cells, effector cell
      derived GzB hydrolyzes the substrate, generating a fluorescent signal that allows
      individual target cells that have received a lethal hit to be identified by flow
      cytometry. Results are reported as the percentage of target cells with GzB
      activity (%GzB). Freshly isolated or cryopreserved PBMC and/or NK cells can be
      used as effector cells. CEM.NKR cells expressing the CCR5 co-receptor are used as
      a target cells following: (i) coating with recombinant envelope glycoprotein,
      (ii) infection with infectious molecular clones expressing the Env antigens of
      primary and lab adapted viruses, or (iii) chronic infection with a variant of HIV
      1/IIIB, termed A1953. In addition, primary CD4(+) T cells infected with HIV-1 in
      vitro can also be used as targets. The assay is highly reproducible with a
      coefficient of variation of less than 25%. Target and effector cell populations,
      in the absence of serum/plasma, were used to calculate background (8.6 +/- 2.3%).
      We determined that an initial dilution of 1:50 and 1:100 is required for testing
      of human and non-human primate samples, respectively. This assay allows for rapid
      quantification of HIV-1 or SIV-specific ADCC-mediating antibodies that develop in
      response to vaccination, or in the natural course of infection, thus providing
      researchers with a new methodology for investigating the role of ADCC-mediating
      antibodies as correlates of control or prevention of HIV-1 and SIV infection.

PMID- 21735547
TI  - Preparation of epoxy-based macroporous monolithic columns for the fast and
      efficient immunofiltration of Staphylococcus aureus.
AB  - Macroporous epoxy-based monolithic columns were used for immunofiltration of
      bacteria. The prepared monolithic polymer support is hydrophilic and has large
      pore sizes of 21 MUm without mesopores. A surface chemistry usually applied for
      immobilization of antibodies on glass slides is successfully transferred to
      monolithic columns. Step-by-step, the surface of the epoxy-based monolith is
      hydrolyzed, silanized, coated with poly(ethylene glycol diamine) and activated
      with the homobifunctional crosslinker di(N-succinimidyl)carbonate for
      immobilization of antibodies on the monolithic columns. The functionalization
      steps are characterized to ensure the coating of each monolayer. The prepared
      antibody-immobilized monolithic column is optimized for immunofiltration to
      enrich Staphylococcus aureus as an important food contaminant. Different kinds of
      geometries of monolithic columns, flow rates and elution buffers are tested with
      the goal to get high recoveries in the shortest enrichment time as possible. An
      effective capture of S. aureus was achieved at a flow rate of 7.0 mL/min with low
      backpressures of 20.1+/-5.4 mbar enabling a volumetric enrichment of 1000 within
      145 min. The bacteria were quantified by flow cytometry using a double-labeling
      approach. After immunofiltration the sensitivity was significantly increased and
      a detection limit of the total system of 42 S. aureus/mL was reached. 

PMID- 21735548
TI  - Quantitative structure-retention relationship of new N-substituted 2-alkylidene-4
      oxothiazolidines.
AB  - A quantitative structure-retention relationship (QSRR) was built to investigate
      the relationship between the structural descriptors of 23 newly synthesized N
      substituted 2-alkylidene-4-oxothiazolidines and their chromatographic retention.
      Retention was investigated by means of the reversed-phase thin-layer
      chromatography (RP-TLC) on the C(18) and CN stationary phases, using methanol,
      acetonitrile, and tetrahydrofuran as organic modifiers. Full geometry
      optimization based on the Austin Model 1 (AM1) semi-empirical molecular orbital
      method was carried out and a set of physicochemical molecular descriptors was
      calculated from the optimized structures. QSRR was built by means of multiple
      linear regression (MLR) and partial least squares regression (PLS). The best MLR
      and PLS models were chosen, on the basis of comparison of the statistical
      parameters (squared correlation coefficient (R(2)), cross-validated coefficient
      (R(cv)(2)), and Fischer significance value (F) were used for MLR and the square
      of the multiple correlation coefficients for the calibration objects (R(2)Y
      (cum)) and the square of the multiple correlation coefficients for the cross
      validation segments (Q(2)Y (cum)) were used for PLS models). Statistically
      significant and physically meaningful QSRR provided better insight on
      understanding the retention behavior of the new series of compounds. Lipohilicity
      (expressed as log P) was included in all MLR and PLS models.

PMID- 21735549
TI  - Fast CEC-MS using poly(dimethylsiloxane) microinjector, short packed column, and
      low-sheath-flow interface.
AB  - A fast CEC-MS approach based on a microinjector and a short CEC column was
      developed. Poly(dimethylsiloxane) was used as the substrate for microinjector
      fabrication. A short capillary column (~5 cm) packed with 5 MUm octadecyl silica
      particles was inserted into the microinjector. The microinjector CEC device was
      interfaced to ESI-MS using a low-flow sheath liquid interface. The device
      delivers the advantages of sample introduction, pre-concentration, elution, and
      fast analysis as in chip-CEC yet avoids the difficulty of packing stationary
      material into the chip. The online pre-concentration and CEC-MS analysis
      capabilities of this device were demonstrated by analysis of a six-triazine
      mixture. A signal enhancement of 20-99-fold was achieved with a sample loading
      time of 180 s.

PMID- 21735550
TI  - Simultaneous determination of vinblastine and its monomeric precursors vindoline
      and catharanthine in Catharanthus roseus by capillary electrophoresis-mass
      spectrometry.
AB  - Catharanthus roseus is an important dicotyledonous medicinal plant that contains
      various anticancer components, such as vinblastine (VLB) and its monomeric
      precursors (vindoline and catharanthine). A capillary electrophoresis-mass
      spectrometry (CE-MS) approach for the simultaneous determination of three
      components was developed in this work. Baseline separation for three components
      was achieved by using a running buffer consisting of 20 mM ammonium acetate and
      1.5% acetic acid in <20 min. Quantification of three components was assigned in
      positive-ion mode at a protonated molecular ion [M+H](+). The CE-MS method was
      validated for linearity, sensitivity, accuracy and precision, and then used to
      determine the content of the above components. The detection limits of VLB,
      catharanthine and vindoline are 0.8, 0.1 and 0.1 MUg/mL, respectively. The
      precision was not more than 4.54% and the mean recovery of the analytes was 95.04
      97.04%. The CE-MS method was successfully applied to determine VLB and its
      monomeric precursors in real sample C. roseus.

PMID- 21735551
TI  - Optimum conditions for the water extraction of L-theanine from green tea.
AB  - Theanine is a unique non-protein amino acid found in tea (Camellia sinensis). It
      contributes to the favourable umami taste of tea and is linked to various
      beneficial effects in humans. There is an increasing interest in theanine as an
      important component of tea, as an ingredient for novel functional foods and as a
      dietary supplement. Therefore, optimal conditions for extracting theanine from
      tea are required for the accurate quantification of theanine in tea and as an
      efficient first step for its purification. This study examined the effects of
      four different extraction conditions on the yield of theanine from green tea
      using water and applied response surface methodology to further optimise the
      extraction conditions. The results showed that temperature, extraction time,
      ratio of water-to-tea and tea particle sizes had significant impacts on the
      extraction yield of theanine. The optimal conditions for extracting theanine from
      green tea using water were found to be extraction at 80  degrees C for 30 min
      with a water-to-tea ratio of 20:1 mL/g and a tea particle size of 0.5-1 mm.

PMID- 21735553
TI  - Tuning the excited state of photoactive building blocks for metal-templated self
      assembly.
AB  - The reaction of 2,2':4,4'':4',4'''-quaterpyridyl (qtpy), with d(6) ruthenium(II)
      (Ru(II) ), and rhenium(I) (Re(I) ) metal centers has been investigated. The
      pendant pyridyl groups on the products have also been methylated to produce a
      second series of complexes containing coordinated Meqtpy(2+). The absorption
      spectra of the complexes are dominated by intraligand and charge-transfer bands.
      The ruthenium(II) complexes display broad unstructured luminescence consistent
      with emission from a Ru(d)->diimine(pi*) manifold in acetonitrile solutions. In
      aqueous solutions, their emissions are weaker and the lifetimes are shorter. This
      effect is particularly acute for complexes incorporating coordinated
      dipyridylpyrazine, dppz, ligands. Although the emission of the ruthenium(II)
      complexes containing Meqtpy(2+) is generally shorter than their qtpy analogs, it
      is notable that solvent-dependent effects are much less intense. The rhenium(I)
      complexes also display broad unstructured luminescence but, compared with the
      ruthenium(II) systems, they have a relatively short lifetime in acetonitrile.
      Electrochemical studies reveal that all of the Ru(II) complexes display
      chemically reversible metal-based oxidations. Re(I) complexes only display
      irreversible metal-based oxidations. In most cases, the reduction processes were
      not fully chemically reversible. The electrochemical and optical studies reveal
      that the nature of the lowest excited state of these complexes--particularly, the
      systems incorporating dppz--is highly dependent on the nature of the coordinated
      ligands. Calculations indicate that, although the excited state of most of the
      complexes is centered on the qtpy or Meqtpy(2+) ligands, the excited state of the
      complexes containing dppz ligands is switched away from the dppz by qtpy
      methylation. A crystallographic study on one of the dicationic ruthenium(II)
      structures reveals that it forms an inclusion complex with benzene.

PMID- 21735552
TI  - Intestinal mucosal adherence and translocation of commensal bacteria at the early
      onset of type 2 diabetes: molecular mechanisms and probiotic treatment.
AB  - A fat-enriched diet modifies intestinal microbiota and initiates a low-grade
      inflammation, insulin resistance and type-2 diabetes. Here, we demonstrate that
      before the onset of diabetes, after only one week of a high-fat diet (HFD), live
      commensal intestinal bacteria are present in large numbers in the adipose tissue
      and the blood where they can induce inflammation. This translocation is prevented
      in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but
      overtly increased in Myd88 knockout and ob/ob mouse. This 'metabolic bacteremia'
      is characterized by an increased co-localization with dendritic cells from the
      intestinal lamina propria and by an augmented intestinal mucosal adherence of non
      pathogenic Escherichia coli. The bacterial translocation process from intestine
      towards tissue can be reversed by six weeks of treatment with the probiotic
      strain Bifidobacterium animalis subsp. lactis 420, which improves the animals'
      overall inflammatory and metabolic status. Altogether, these data demonstrate
      that the early onset of HFD-induced hyperglycemia is characterized by an
      increased bacterial translocation from intestine towards tissues, fuelling a
      continuous metabolic bacteremia, which could represent new therapeutic targets.

PMID- 21735554
TI  - Counterion-mediated hydrogen-bonding effects: mechanistic study of gold(I)
      catalyzed enantioselective hydroamination of allenes.

PMID- 21735555
TI  - Tandem one-pot Wittig/reductive aldol reactions in which the waste from one
      process catalyzes a subsequent reaction.

PMID- 21735556
TI  - Dienamine activation in the organocatalytic asymmetric synthesis of cis-3,4
      difunctionalized chromans and dihydrocoumarins.

PMID- 21735557
TI  - Demystifying the Millennial student: a reassessment in measures of character and
      engagement in professional education.
AB  - The characteristic profile of Millennial Generation students, driving many
      educational reforms, can be challenged by research in a number of fields
      including cognition, learning style, neurology, and psychology. This evidence
      suggests that the current aggregate view of the Millennial student may be less
      than accurate. Statistics show that Millennial students are considerably diverse
      in backgrounds, personalities, and learning styles. Data are presented regarding
      technological predilection, multitasking, reading, critical thinking,
      professional behaviors, and learning styles, which indicate that students in the
      Millennial Generation may not be as homogenous in fundamental learning strategies
      and attitudes as is regularly proposed. Although their common character traits
      have implications for instruction, no available evidence demonstrates that these
      traits impact their fundamental process of learning. Many curricular strategies
      have been implemented to address alleged changes in the manner by which
      Millennial students learn. None has clearly shown superior outcomes in academic
      accomplishments or developing expertise for graduating students and concerns
      persist related to the successful engagement of Millennial students in the
      process of learning. Four factors for consideration in general curricular design
      are proposed to address student engagement and optimal knowledge acquisition for
      21st century learners.

PMID- 21735558
TI  - Succinate production from sucrose by metabolic engineered Escherichia coli
      strains under aerobic conditions.
AB  - Two metabolically engineered E. coli strains HL2765k and HL27659k, while capable
      of producing succinate from glucose with high yields, are not able to grow and
      produce succinate on sucrose. Consequently, the pUR400 plasmid containing scrK,
      Y, A, B, and R genes was introduced into HL2765k and HL27659k, respectively.
      Shake flask culture studies showed that the resulting strains can utilize
      sucrose; the strain HL2765k pUR400 and HL27659k pUR400 can produce succinate
      aerobically with a molar yield of 0.78 +/- 0.02 mol/mol and 1.35 +/- 0.13
      mol/mol, respectively. On introduction of the plasmid pHL413, which encodes the
      heterologous pyruvate carboxylase (PYC) from Lactococcus lactis, the molar
      succinate yield increased to 1.60 +/- 0.01 mol of succinate per mole of sucrose
      by the HL2765k pUR400 pHL413 strain and to 1.84 +/- 0.10 by the HL27659k pUR400
      pHL413 strain. In aerobic batch bioreactor studies, the succinate production rate
      was faster, and succinate production reached 101.83 mM with a yield of 1.90 when
      dissolved oxygen (DO) was controlled at 40 +/- 7%. In addition, the results
      showed that DO had an important effect on succinate production by influencing PYC
      activity. This work demonstrates the possibility of producing succinate
      aerobically using sucrose as the carbon source.

PMID- 21735559
TI  - GPU-accelerated atom and dynamic bond visualization using hyperballs: a unified
      algorithm for balls, sticks, and hyperboloids.
AB  - Ray casting on graphics processing units (GPUs) opens new possibilities for
      molecular visualization. We describe the implementation and calculation of
      diverse molecular representations such as licorice, ball-and-stick, space-filling
      van der Waals spheres, and approximated solvent-accessible surfaces using GPUs.
      We introduce HyperBalls, an improved ball-and-stick representation replacing
      tubes, linking the atom spheres by hyperboloids that can smoothly connect them.
      This type of depiction is particularly useful to represent dynamic phenomena,
      such as the evolution of noncovalent bonds. It is furthermore well suited to
      represent coarse-grained models and spring networks. All these representations
      can be defined by a single general algebraic equation that is adapted for the ray
      casting technique and is well suited for execution on the GPU. Using GPU
      capabilities, this implementation can routinely, accurately, and interactively
      render molecules ranging from a few atoms up to huge macromolecular assemblies
      with more than 500,000 particles. In simple cases, based only on spheres, we have
      been able to display up to two million atoms smoothly.

PMID- 21735560
TI  - Ab initio molecular dynamics of protonated water clusters by integrated
      multicenter molecular-orbital method.
AB  - To analyze large-scale cluster systems theoretically, we recently developed an
      "integrated multicenter molecular-orbital" (IMiC-MO) method. This method
      calculates the force of an entire system by dividing the system into small
      regions. We used the method to analyze the effect of cluster size and the process
      of hydrogen bond network (HBN) growth to form H(+)(H(2)O)(n) (n = 9, 17, and 33)
      clusters. Our simulations reveal that H(3)O(+) and water molecules in the first
      solvation shell function take an important role to grow the HBN. In addition, the
      number of hydrogen donors in each water molecule is strongly related to the shape
      of the HBN.

PMID- 21735613
TI  - Yearning, learning, and conceding: reasons men and women change their
      childbearing intentions.
AB  - People's childbearing intentions change over the course of their reproductive
      lives. These changes have been conceptualized as occurring in response to the
      realization that an individual is unlikely to achieve his or her intended
      fertility, because of constraints such as the "biological clock" or lack of a
      partner. In this article, we find that changes to child-bearing plans are
      influenced by a much wider range of factors than this. People change their plans
      in response to the wishes of their partners, in response to social norms, as the
      result of repartnering, and as the result of learning about the costs and
      benefits of parenthood; there are also differences between the factors that
      influence men's and women's decision-making. In a departure from existing studies
      in this area, we use a flexible analytical framework that enables us to analyze
      increases in planned fertility separately from decreases. This allows us to
      uncover several complexities of the decision-making process that would otherwise
      be hidden, and leads us to conclude that the determinants of increases in planned
      fertility are not simply equal and opposite to the determinants of decreases.

PMID- 21735614
TI  - Socioeconomic marriage differentials in Australia and New Zealand.
AB  - While marriage rates are relatively stable among better-educated men and women,
      they are rapidly declining among those with low educational attainment. This
      development has been recognized in the US as a new socioeconomic pattern of
      marriage. This article uses census data to show that socioeconomic marriage
      differentials are also increasing in Australia and New Zealand. These
      differentials have previously been noted independently of each other and of the
      international picture. In synthesizing the antipodean data, the article documents
      the new socioeconomic marriage pattern as an international phenomenon. This
      article further considers the extent to which the available explanations for the
      new marriage pattern fit the antipodean setting. In general, the factors
      identified as important in the North American setting are applicable to both
      Australia and New Zealand. In particular, the poor marriage prospects of men with
      low educational attainment appear to be common to these post-industrial economies
      with minimalist welfare states.

PMID- 21735615
TI  - The demise of the American Indios.
AB  - This symposium takes as its point of departure two books by Massimo Livi Bacci,
      Conquest and El Dorado in the Marshes, published in English in 2008 and 2010.
      Livi Bacci assesses widely varying estimates of the demographic dimensions of the
      collapse of the Native populations following their contact with Europeans and
      elucidates the proximate causes of that catastrophe. Drawing on models that
      combine production potential with demography, environment, and technology,
      Shripad Tuljapurkar discusses analogous historical experiences of the populations
      of Polynesia and the social transformation they entailed. David S. Reher argues
      that explanations of the estimated demographic dynamics need to take into account
      the negative fertility responses of the Indigenous population to the disruption
      of their traditional way of life. Focusing on the biological aspects of immunity
      to diseases such as smallpox, Andrew Noymer demonstrates that infectious diseases
      alone could not account for the Indios' population collapse. The contributions to
      this symposium are based on presentations at a session at the 2010 annual meeting
      of the Population Association of America, held in Dallas, Texas, that examined
      the demographic consequences of the Spanish conquest of the Caribbean region and
      of South America in light of the two books.

PMID- 21735616
TI  - Demography as the human story.

PMID- 21735617
TI  - Reflections on the fate of the Indigenous populations of America.

PMID- 21735618
TI  - Population decline in post-conquest America: the role of disease.

PMID- 21735619
TI  - Death and disease in the prisons of colonial Burma.

PMID- 21735620
TI  - Bitter pills: colonialism, medicine and nationalism in Burma, 1870-1940.

PMID- 21735621
TI  - The scientific and hygienic housewife-and-mother: education, consumption and the
      discourse of domesticity.

PMID- 21735622
TI  - Transmission.  Company halts Truvada PrEP for women study.

PMID- 21735623
TI  - Prevention.  HIV programs need to be revamped for juvenile offenders.

PMID- 21735624
TI  - Asylum.  Man cannot show he'd be persecuted for HIV, homosexuality.

PMID- 21735625
TI  - Employment.  No proof that HIV medications caused man to fail drug test.

PMID- 21735626
TI  - [Planned management and still allowing room for trial and error].

PMID- 21735627
TI  - [The mountain peak nurse (interview by Christian Heinemeyer)].

PMID- 21735628
TI  - [The urinary and fecal incontinence taboo topic: counseled well, secure travel].

PMID- 21735629
TI  - [Urinary and fecal incontinence in patients with dementia: where now was the
      toilet"?].

PMID- 21735630
TI  - [Dancing while sitting: quality of life and health training: singing, swinging,
      swaying].

PMID- 21735631
TI  - [Hygienic aspects of wound management: not just clean, but disinfected].

PMID- 21735632
TI  - [Violence - (not) an issue in health care facilities: almost everyone is affected
      - almost all are silent].

PMID- 21735633
TI  - [Model project improves nursing home physician access: step by step to optimal
      medical care].

PMID- 21735634
TI  - [Irrigating the long-term bladder catheter in adults: what method is the best?].

PMID- 21735635
TI  - [Pressure in nursing care: Outcomes of a prevalence study of pressure ulcers in
      Austrian hospitals and nursing homes].
AB  - For decades pressure ulcers have been internationally serious and frequent
      nursing relevant problems. It causes enormous suffering to the affected and high
      costs for society. Prevalence studies about pressure ulcers indicate the extent
      of this disease. Subsequently targeted measures can be planned in order to
      prevent pressure ulcers. There are already some international prevalence surveys
      of pressure ulcers, which reported prevalence data from 0.06 per cent to 83.6 per
      cent in hospitals and nursing homes. A comparison of these studies is limited due
      to their differences in methodology, population and the definition of prevalence
      and pressure ulcer. Prevalences for pressure ulcers were hardly available so far
      in Austria. Therefore in the context of the National Prevalence Survey Care
      related Data (LPZ) prevalence data, quality indicators and data on the prevention
      and treatment of pressure ulcers were standardized collected with a
      scientifically tested questionnaire for the first time in austrian health
      institutions. This survey entitles to compare the results between participating
      institutions and countries. 2353 hospital patients and nursing home residents in
      17 austrian institutions participated. The prevalence in the risk group was 12.2
      per cent (excluding grade one pressure ulcer: eight percent) forthe patients and
      seven per cent (excluding grade one pressure ulcer: 5.9 Prozent) for the
      residents. Most of the wounds were acquired on the heels. This study also found
      that prevention activities of pressure ulcers were used more often in the nursing
      homes than in hospitals. Compared to the prevalence of published studies the
      identified prevalence of pressure ulcers is low. Regular participation in
      prevalence surveys is advisable, so that institutions examine themselves
      objectively in terms of quality of care as well.

PMID- 21735636
TI  - [Work safety: overview of your rights and responsibilities: even the toilets are
      included with their own guideline].

PMID- 21735637
TI  - [Challenges for management and administration: conquering incontinence - but
      how?].

PMID- 21735638
TI  - [Nursing diagnosis in practice and education: dealing with chances responsibly].

PMID- 21735639
TI  - [Amalie Sieveking - pioneer in indigent and sickness nursing: the suffering of
      cholera patients aroused the merchant's daughter].

PMID- 21735640
TI  - [From case to case: what all the kidney can do!].

PMID- 21735641
TI  - [Diabetes: almost half the patient are inadequately adjusted - an action program
      offers a risk checkup].

PMID- 21735642
TI  - [Improved microstimulation system introduced. Optimized prevention of decubitus
      ulcer].

PMID- 21735643
TI  - [Expressions of aquaporins 1 and 3 in the mouse prostate and their significance].
AB  - OBJECTIVE: To investigate the expressions of aquaporins (AQPs) in the mouse
      prostatic tissue and their significance, and to provide some evidence for a
      deeper insight into the physiological function and regulation of AQP expressions
      in normal and diseased prostatic tissues. METHODS: The mRNA expressions of AQP0 -
      4 in the mouse prostatic tissue were determined by RT-PCR, and the expressions
      and localizations of AQP1 and AQP3 proteins were characterized by Western blot
      and immunohistochemistry. RESULTS: RT-PCR exhibited the mRNA expressions of AQP1
      and AQP3, but not those of AQP0, AQP2 and AQP4 in the prostate tissue, while
      Western blot showed the expression of the AQP1 protein with the relative
      molecular mass (RMM) of 28 000 and those of the glycosylated and non-glycosylated
      AQP3 proteins with the RMM of 35 000 and 27 000, respectively.
      Immunohistochemistry indicated the strong expression of AQP1 in the cyst and
      plasma membrane of the secretary cells and that of AQP3 in the stroma cells of
      the prostate. CONCLUSION: The AQP1 and AQP3 genes were expressed in the secretary
      epithelia of the mouse prostate tissue, which suggests that AQP1 and AQP3 may
      play an important role in the secretion of prostatic fluid.

PMID- 21735644
TI  - [An investigation on female sexual dysfunction among urban Chinese women in
      Nanjing].
AB  - OBJECTIVE: Female sexual dysfunction (FSD) is a common problem affecting women's
      quality of life. However, reports are rarely seen on sexual problems in Chinese
      women. This study is to investigate the prevalence of FSD among urban Chinese
      women in Nanjing and offer some evidence for the establishment of preventative
      measures for FSD in China. METHODS: A cross-sectional hospital-based survey was
      conducted in Nanjing, China between August 2008 and March 2009. The sexual
      function of 609 women aged 20 -56 years from the urban area of Nanjing were
      investigated using the Female Sexual Function Index (FSFI). The total FSFI score
      of < 25 was used as the diagnostic criterion for FSD. RESULTS: The total FSFI
      score was 24.21 +/- 4.40 in this group of women, and it decreased with the
      increase of age. The overall prevalence of FSD was 56.8%, and it increased with
      the increase of age, 47.1%, 57.0%, 75.0% and 90.3% in the < 29 yr, 30 - 39 yr, 40
      - 49 yr and > or = 50 yr groups, respectively. The most common problems were low
      sexual satisfaction (43.2%) and orgasm disorder (41.7%), followed by sexual pain
      (40.2%), hyposexuality (35.1%), vaginal dryness (31.4%) and sexual arousal
      disorder (29.6%). CONCLUSION: FSD is a common problem among urban Chinese women
      in Nanjing, and the most common sexual problems are low sexual satisfaction and
      orgasm disorder.

PMID- 21735645
TI  - [Leptin level in azoospermic patients and its clinical value].
AB  - OBJECTIVE: To detect the levels of seminal plasma leptin (SPL) and serum leptin
      (SL) in patients with azoospermia, and to explore the methods of using SPL and SL
      alone or the combination of SPL, SL and follicle stimulating hormone (FSH) for
      the differential diagnosis of obstructive azoospermia (OA) and non-obstructive
      azoospermia (NOA). METHODS: We enrolled in this study 45 patients with diagnosed
      OA, 41 with unexplained NOA and 30 men with normal semen parameters as controls.
      The azoospermia patients underwent percutaneous aspiration from the epididymis
      (PESA) or aspiration/extraction from the testis (TESA/TESE), and all the subjects
      were detected for the levels of serum FSH, SPL and SL. Individual and multiple
      indexes were evaluated by Fisher's discriminant analysis combined with ROC curve
      analysis. RESULTS: There were no significant differences in the body mass index
      (BMI) among the three groups. Compared with the normal control, the OA patients
      showed an obviously elevated level of SPL (P = 0.048), and the NOA patients
      remarkably increased levels of FSH (P = 0.000), SL (P = 0.000) and SPL (P =
      0.000). In comparison with the OA group, the levels of FSH (P = 0.000), SL (P =
      0.006) and SPL (P = 0.033) were significantly increased in the NOA group. For the
      differential diagnosis of OA and NOA, the areas under the ROC curve of SPL and SL
      were 0.658 (P = 0.014) and 0.702 (P = 0.002) , respectively, both significantly
      greater than 0.5, while that of the combination of SPL, SL and FSH was the
      greatest (0.953). In addition, with 0.026 x SPL +0.05 x SL +0.106 x FSH -2.197 as
      the combined indicator value and -0.289 as the cut-off value (> or = cut-off
      value for NOA), the sensitivity and specificity of the combination were 0.878 and
      0.902, respectively, both reached the maximum. CONCLUSION: Both the levels of SPL
      and SL are valuable for the differential diagnosis of OA and NOA, but the joint
      consideration of SPL, SL and FSH may provide better indicators.

PMID- 21735646
TI  - [Anti-Mullerian hormone in male serum and prediction of the outcomes of assisted
      reproductive technology].
AB  - OBJECTIVE: To evaluate male serum anti-Mullerian hormone (AMH) in assessing semen
      quality and predicting the pregnancy outcomes of assisted reproductive technology
      (ART). METHODS: A total of 103 male patients under ICSI were allotted to Groups A
      (normal sperm concentration control, n = 29), B (oligospermia, n = 27), C
      (obstructive azoospermia, n = 29) and D (non-obstructive azoospermia, n = 18).
      The contents of serum AMH and other related sexual hormones were determined by
      ELISA, and their correlations were analyzed with the seminal quality on the day
      of semen collection and with the pregnancy outcomes after ICSI. RESULTS: The
      contents of male serum AMH were (5.03 +/- 0.44), (3.70 +/- 0.44), (5.39 +/- 0.71)
      and (7.31 +/- 1.64) pmol/L, respectively, in Groups A, B, C and D, with no
      statistically significant differences among the four groups (F = 2.02, P > 0.05).
      The egg fertilization rate of the 103 couples was (76.13 +/- 23.66) %, not
      significantly correlated with the male serum AMH level (P > 0.05). The contents
      of male serum AMH in the pregnancy and non-pregnancy groups were (6.19 +/- 1.05)
      and (4.72 +/- 1.64) pmol/L, respectively, with no significant difference (t =
      1.281, P > 0.05). CONCLUSION: The level of male serum AMH can neither reflect
      spermatogenesis of men nor predict the egg fertilization rate and pregnancy
      outcomes after ICSI, and therefore cannot be used alone as a serological
      predictive marker of ICSI outcomes.

PMID- 21735647
TI  - [Transrectal ultrasonography in the etiological diagnosis of male obstructive
      azoospermia: analysis of 695 cases].
AB  - OBJECTIVE: To assess the role of transrectal ultrasonography (TRUS) in the
      etiological diagnosis of male obstructive azoospermia. METHODS: We
      retrospectively analyzed the clinical data and TRUS findings of 695 patients with
      obstructive azoospermia from January 2007 to May 2009. RESULTS: Concerning the
      etiology of obstructive azoospermia, the main TRUS findings included ejaculatory
      duct abnormality (29.2%), seminal vesicle abnormality (25.4%) and prostate
      midline cyst (18.5%). TRUS revealed 203 cases of ejaculatory duct dilation, 177
      cases of seminal vesicle abnormality (including 108 with absence or agenesis and
      51 with dilation of the seminal vesicle), and 128 cases of prostate midline cyst
      (including 75 with ejaculatory duct cyst and 39 with Mullerian cyst).
      Calcification of the verumontanum or ejaculatory duct was suspected to be the
      causes of obstructive azoospermia in 34 cases. However, no significant
      etiological abnormality was found in 153 cases. Obvious etiology was shown by
      TRUS in 78.0% of the patients. CONCLUSION: TRUS can clearly display the
      structural abnormality of the ejaculatory duct and seminal vesicle, and provide
      important information on the etiology of male obstructive azoospermia.

PMID- 21735648
TI  - [Testosterone-induced spermatogenic impairment is associated with looser
      arrangement of spermatogenic cells in rats].
AB  - OBJECTIVE: To determine whether testosterone-induced intra-testicular
      testosterone withdrawal and therefore spermatogenic impairment is associated with
      looser arrangement of spermatogenic cells in rats. METHODS: Adult male SD rats
      received intramuscular injection of testosterone undecanoate at 19 mg/(kg x 15 d)
      for 130 days, and then testicular tissue blocks were obtained for the preparation
      of methacrylate resin-embedded sections and observation of the changes in
      testicular histology. RESULTS: Apart from such changes as impaired spermiogenesis
      and spermiation, apparently looser arrangement of spermatogenic cells was seen in
      11.5% of the seminiferous tubule profiles, with radial cracks (empty spaces)
      running towards the tubule lumen being formed between lines, bundles or groups of
      spermatogenic cells (mainly spermatids and spermatocytes). CONCLUSION: Looser
      arrangement of spermatogenic cells is one of the key histological changes
      resulting from intra-testicular testosterone withdrawal in rats.

PMID- 21735649
TI  - [Semen quality analysis of 2 640 infertile men in Suzhou area].
AB  - OBJECTIVE: To study the semen quality of male infertility patients in Suzhou
      area, China. METHODS: We detected the semen quality of 2 640 infertility patients
      in Suzhou area using computer-assisted semen analysis technology. RESULTS: Of the
      2 640 semen samples, 27.35% were found normal in all seminal indexes, 47.35% (1
      250/2 640) abnormal in the percentage of grade a + b sperm, and 42.39% (1 119/2
      640) abnormal in sperm motility. The percentage of grade a + b sperm and sperm
      motility were decreased with the increase of age, more obviously in those over 40
      years. The incidences of asthenospermia and oligospermia were 37.31% (985/2 640)
      and 8.94% (236/2 640), rising with the increase of age, especially in those older
      than 30 years. The 9 sperm motion parameters, including VSL, VCL, LIN, MAD, VAP,
      STR, WOB, ALH and BCF, were significantly reduced with the decrease of sperm
      motility and sperm concentration. CONCLUSION: The infertile men in Suzhou area
      are mainly characterized by a decrease in sperm motility, especially in the
      percentage of grade a + b sperm. The correlation of age with sperm motility and
      incidence of asthenospermia and oligospermia suggests that men also have an
      appropriate childbearing age.

PMID- 21735650
TI  - [Expression of annexin A7 in spermatogonial stem cells].
AB  - OBJECTIVE: To study the expression of Annexin A7 in the mouse testis, especially
      in different types of spermatogonia. METHODS: We prepared Annexin A7 recombinant
      protein using prokaryotic expression, adsorbed the Annexin A7 antibody with it
      after identified by mass spectrometry, and detected the expression of Annexin A7
      by Western-blot and immunohistochemistry. RESULTS: Annexin A7 was expressed in a
      development-dependent manner in the spermatogonia of the prepubertal mice and in
      the type-A single (As) and type-A paired (Apr) spermatogonia of adult mice. These
      results were confirmed by the co-localization of Annexin A7 and Stra8, a known
      determinant of differentiated spermatogonial stem cells (SSCs). CONCLUSION:
      Annexin A7 is the internal factor of As and Apr spermatogonia, which might be
      involved in the biological functions of SSCs.

PMID- 21735651
TI  - [Retropubic radical prostatectomy: 10 years' experience with 100 cases].
AB  - OBJECTIVE: To summarize the experience and lessons from 100 cases retropubic
      radical prostatectomy performed in the past 10 years. METHODS: From July 1999 to
      July 2009, we performed 100 cases of retropubic radical prostatectomy, of which
      84 were followed up for 3 - 120 months. We analyzed their preoperative age, PSA
      level, amount of intraoperative blood transfusion, operation time, urinary
      continence, penile erectile function, stricture of the anastomotic stoma and
      Qmax. RESULTS: The mean age, PSA level, amount of intraoperative blood
      transfusion, operation time were 66.8 yr, 20.1 ng/ml, 585.7 ml and 198.9 min; the
      recovery rates of bladder control at 3, 6 and 12 months postoperatively were
      65.5%, 81.7% and 92.4%, respectively. At 12 months after surgery, penile erection
      was restored in 19 cases (42.2%), anastomotic stoma stricture developed in 5
      (5.9%), Qmax averaged 20.5 ml/min, biochemical recurrence was found in 13, and 1
      died from prostate cancer. CONCLUSION: Retropubic radical prostatectomy is a
      desirable procedure for the treatment of local prostate cancer, in which ligation
      of the puboprostatic ligament and prostatic venous plexus before cutting off the
      ligament helps improve urinary continence, protection of the neurovascular bundle
      and collateral pudendal artery contributes to the recovery of penile erectile
      function, and proper connection of urethral and bladder mucosa can reduce
      anastomotic stoma stricture. Postoperative external-beam radiotherapy for those
      with T3a or local lymph node metastasis could decrease biochemical recurrence.

PMID- 21735652
TI  - [Prostatic middle lobe hyperplasia correlates with bladder outflow obstruction:
      analysis of 131 cases].
AB  - OBJECTIVE: To analyze the correlation between the size of prostatic middle lobe
      hyperplasia and the degree of bladder outlet obstruction (BOO) in patients with
      benign prostatic hyperplasia (BPH). METHODS: This study included 131 BPH patients
      who presented with dysuria between May 2008 and June 2010. The prostate volume
      and intravesical prostatic protrusion (IPP) were measured by transabdominal
      ultrasound, Qmax and detrusor pressure at Qmax (P(det@ Qmax)) detected by
      urodynamic examination, the obstruction degree and detrusor contractility judged
      using the LinPURR Figure, and the AG value calculated (AG = P(det@ Qmax) -2Qmax).
      The degrees of BOO were compared between different groups of IPP by variance
      analysis, and the prostate volume, IPP and AG values underwent Bivariate
      correlation analysis. RESULTS: IPP was highly positively correlated with BOO when
      it was > 10 mm (r = 0.821, P < 0.01), while PV and BOO had a lower correlation (r
      = 0.475, P < 0.01). There was also a high positive correlation between IPP and
      P(det@ Qmax) (r = 0.865, P < 0.01). CONCLUSION: A close correlation exists
      between prostatic middle lobe hyperplasia and BOO, and evaluating IPP by
      ultrasound is a reliable method to determine the degree of BOO.

PMID- 21735653
TI  - [Efficacy and safety of long-term small-dose tadalafil in the treatment of
      erectile dysfunction].
AB  - OBJECTIVE: Erectile dysfunction (ED) is now recognized as a comorbid condition,
      especially in men with cardiovascular disease or diabetes mellitus. This
      randomized controlled trial was to examine the effect of long-term small-dose
      tadalafil in the treatment of ED. METHODS: A total of 98 men older than 18 years
      with at least a 6-month ED history were enlisted and divided into two groups to
      receive once-daily treatment with tadalafil at 5 mg (n = 60) and 20 mg (n = 38),
      respectively, for 12 months. The effects of medication were analyzed and compared
      using IIEF, Global Assessment Questionnaire (GAQ) and Sexual Encounter Profile
      (SEP), and so were the safety and tolerance of the two doses. RESULTS: There were
      no statistically significant differences in the therapeutical results between the
      5 mg and 20 mg groups (P < 0.05). The IIEF-5 score was raised by 8.1 points in
      the former and 7.9 points in the latter; the YES answers to SEP2 in the two
      groups were 51.3% and 49.2% before the treatment and 82.6% and 84.9% after it. No
      serious adverse events were observed, except some common ones, such as rubeosis
      (11.9% vs 8.7%) and headache (5.3% vs 4.9%) in the 5 mg and 20 mg groups.
      CONCLUSION: Oral tadalafil at 5 mg once daily is efficacious with good tolerance
      in the treatment of ED, and it can be an alternative to on-demand medication for
      some men to eliminate the inconvenience of planned intercourse within a limited
      timeframe.

PMID- 21735654
TI  - [Treatment of penile strangulation and sexual psychological analysis of the
      patients].
AB  - OBJECTIVE: To find the best treatment of penile strangulation and to analyze the
      sexual psychological factors of the patients. METHODS: We retrospectively
      analyzed the experiences in removing foreign objects around the penis in 21
      patients aged 19 - 61 years with the strangulation time varying from 10 hours to
      4 days. The objects were mostly made of metal or plastics. RESULTS: All the
      objects were successfully removed, 5 of them with the help of lubricant, 4 by
      aspirating the corpus cavernosum, 8 by shipping with pliers, 2 with the diamond
      tipped dental drill, and the other 2, which virtually defied cutting, by
      aspirating the corpus cavernosum following degloving surgery. CONCLUSION: In
      removing foreign objects around the penis, simpler methods should be given
      precedence over more complex ones, and for those that virtually defy cutting, the
      best option is degloving surgery with particular attention to the survival of the
      penile skin flap.

PMID- 21735655
TI  - [Safety and efficacy of tramadol hydrochloride with behavioral modification in
      the treatment of premature ejaculation].
AB  - OBJECTIVE: To evaluate the efficacy and safety of tramadol hydrochloride with
      behavioral modification in delaying ejaculation in patients with premature
      ejaculation. METHODS: Seventy-two potent men with premature ejaculation were
      equally and randomly assigned to a treatment group and control group, the former
      received 50 mg tramadol hydrochloride with behavioral modification approximately
      2 hours before planned sexual activity, while the latter underwent behavioral
      therapy only, both treated for 8 weeks. Intravaginal ejaculatory latency time
      (IELT), intercourse satisfaction of the partners, total therapeutic
      effectiveness, adverse reactions, and hepatic and renal function of the patients
      were recorded and compared before and after the treatment. RESULTS: Both the
      treatment and the control groups showed significant differences from pretreatment
      in the mean IELT and intercourse satisfaction domain values (P < 0.01). The total
      rate of effectiveness was 72.2% in the treatment group and 47.2% in the control.
      The former exhibited even more significant improvement than the latter in the
      mean IELT, intercourse satisfaction domain values and total rate of effectiveness
      (P < 0.05). Adverse reactions occurred in 10 cases (27.8%), and no statistically
      significant differences were found in hepatic and renal function before and after
      treatment (P > 0.05). CONCLUSION: Tramadol hydrochloride with behavioral
      modification showed positive effects in prolonging IELT and improving partners'
      intercourse satisfaction. Yet more multicenter and double-blind studies are
      required to evaluate its efficacy and safety as a routine therapy for premature
      ejaculation.

PMID- 21735656
TI  - [Circumcision anastomat in the treatment of phimosis and redundant prepuce in
      children].
AB  - OBJECTIVE: To summarize the experience in the application of circumcision
      anastomat in the treatment of phimosis and redundant prepuce in children.
      METHODS: A total of 551 children with phimosis or redundant prepuce were treated
      by circumcision from 2008 to 2010, 342 with circumcision anastomat and the other
      209 by traditional circumcision. Their clinical data were retrospectively
      analyzed. RESULTS: Compared with traditional circumcision, circumcision with the
      anastomat showed the advantages of less operation time (P < 0.05), fewer
      complications, no need for dressing, and better cosmetic appearance, but it also
      exhibited the disadvantages of longer healing time (P < 0.05) and more obvious
      postoperative pain (P < 0.05). CONCLUSION: Circumcision with the anastomat and
      traditional circumcision for the treatment of phimosis and redundant prepuce in
      children each have their own advantages and disadvantages, but the former is more
      advantageous and more feasible clinically.

PMID- 21735657
TI  - [Association of gr/gr deletion in the AZFc region of Y chromosome with male
      infertility: a meta-analysis].
AB  - OBJECTIVE: To evaluate the association of gr/gr deletion in the AZFc region of Y
      chromosome with idiopathic male infertility using Meta-analysis. METHODS: All
      relevant case-control studies addressing the relationship between gr/gr deletion
      and idiopathic male infertility were identified from PubMed, VIP and CNKI (from
      January 2003 to August 2010). Statistical analyses were performed with the
      RevMan4. 2 software. RESULTS: Twenty eligible articles were selected in this
      study, including 5 246 cases of idiopathic infertility and 4 380 controls. The
      integrated data from the 20 studies revealed a significantly higher frequency of
      gr/gr deletion in the patients than in the controls, with an odds ratio (OR) of
      1.63 (95% CI: 1.23 -2.44) (P = 0.002). However, when the Meta-analysis was
      limited to 16 studies with stricter case and control selection criteria, the
      overall OR increased to 1.84 (95% CI: 1.47 - 2.29) (P < 0.000 01). Thirteen
      studies showed that oligozoospermia patients had a significantly higher frequency
      of gr/gr deletion than controls (OR = 2.12, 95% CI: 1.61 - 2.80) (P < 0.000 01).
      Eight studies showed a significant association between the gr/gr deletion subtype
      without DAZ1/DAZ2 gene copies and spermatogenic impairment (OR = 1.83, 95% CI:
      1.31 - 2.55) (P = 0.000 4), but no statistically significant differences were
      found in the frequency distribution of the gr/gr deletion subtype missing
      DAZ3/DAZ4 gene copies between the patients and controls (OR = 1.43, 95% CI: 0.97 
      2.11) (P = 0.07). CONCLUSION: The present data suggest that gr/gr deletion may be
      one of the risk factors of male infertility.

PMID- 21735658
TI  - [Growth factors and gene therapy for erectile dysfunction].
AB  - Growth factors have a universal bioactivity. Gene therapy is a new strategy in
      dealing with erectile dysfunction (ED). This paper presents an overview on the
      value of growth factors, particularly the vascular epithelial growth factor
      (VEGF) and insulin-like growth factor 1 (IGF-1), in the treatment of ED.

PMID- 21735659
TI  - [Oxytocin and male sexual function].
AB  - Oxytocin (OT) is a female hormone with the main function of facilitating uterine
      contraction and milk ejection. Recent studies show that OT is involved in
      multiple signaling pathways in the central and peripheral nerve system and mainly
      regulates the physiology and activity of reproduction, including male
      reproduction and sexual behavior. The roles of OT in penile erection are bio
      phasic with proerectile effect in the central nerve system while peripherally
      inhibiting erection. OT also mediates ejaculation, post-ejaculatory detumescence
      and the post-orgasm refractory period. OT and OT-receptor in the central nerve
      system will be a new target in the drug development for the treatment of erectile
      dysfunction, while OT intracavernous injection promises to be an effective
      therapy for priapism. This review focuses on the effects of OT on male sexual
      activities.

PMID- 21735660
TI  - [Integrated therapy of traditional Chinese and Western medicine for BPH with
      diabetes mellitus: clinical observation of 52 cases].
AB  - OBJECTIVE: To investigate the effect of the integrated therapy of traditional
      Chinese and Western medicine in the treatment of BPH complicated by diabetes
      mellitus. METHODS: Fifty-two cases of BPH complicated by diabetes mellitus were
      equally randomized to a treatment group and a control group, and both underwent
      transurethral plasmakentic vaporization when fasting glucose was kept at 6.0 -
      8.0 mmol/L, followed by anti-infection, rehydration and semeiologically
      supportive therapies. And both of the two groups received Chinese medicinal
      herbal treatment before and after surgery. RESULTS: Neither of the two groups
      showed postoperative electrolyte disturbance, ketone acidosis, or hypoglycemia.
      The incidences of postoperative constipation, bladder convulsion and urinary
      tract infection were significantly lower in the treatment group than in the
      control group (P < 0.05). CONCLUSION: The integrated therapy of traditional
      Chinese and Western medicine for BPH with diabetes mellitus can not only smoothly
      tide the patients over the perioperative period, but also improve their quality
      of life by reducing postoperative constipation, bladder convulsion and urinary
      tract infection.

PMID- 21735661
TI  - [ED patients and their female partners prefer tadalafil].
AB  - Phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, tadalafil and vardenafil,
      are the first-line drugs for the treatment of erectile dysfunction (ED). Giving
      ED patients the opportunity to try all the three inhibitors can greatly improve
      the treatment compliance of the patient, whereas the majority of ED patients
      prefer one specific drug to the others, frequently tadalafil, irrespective of the
      severity and etiology of the disease, dosing sequence, age of the patient, or
      dose of medication. Female partners exhibit a similar preference for tadalafil,
      which has a significant impact on patients' choice. Due to a 36-hour action of
      tadalafil, patients are allowed to achieve erection within a flexible window of
      treatment, and not required to schedule the interval between dosing and sexual
      attempt. The simultaneously decreased time concern will improve the psychological
      well-being of ED patients and their interpersonal relationship with female
      partners. Partners who prefer tadalafil feel a return to relaxed and natural
      sexual activity and the overall improvement in quality of sexual life. The
      preference of patients and their partners for a specific PDE5 inhibitor should be
      considered for the purpose of prescription in clinical practice.

PMID- 21735662
TI  - [Results of treatment of 101 otogenic brain abscesses--56-years experience].
AB  - INTRODUCTION: Inflammatory process in the areas of the middle ear creates a
      possible danger related with the development of extratemporal and intratemporal
      complications. The most dangerous of those include meningitis and cerebral
      abscesses, which are still present. AIM: The aim of the work is to present 101
      patients with cerebral, in temporal lobe, and cerebellar abscesses of aural
      origin throughout the period of 56 years, namely between 1953 and 2009. MATERIAL
      AND METHOD: Data concerning the patients have been obtained retrospectively on
      the basis of medical files. The analysis covered otolaryngological and
      neurological examinations, as well as method related with diagnosing abscesses.
      The thesis distinguished three periods of diagnosing otogenic brain abscess,
      depending on available diagnostic techniques. The first period covers the years
      1956-1978, when constituted the basis of diagnosis. During the second period,
      falling between 1979 and 1989, the diagnosis was based on computed tomography of
      the head, while within the third period, including the years between 1990 and
      2009, diagnosis focused on nuclear magnetic resonance. During the last two years
      neuronavigation was utilized for puncturing abscesses. CONCLUSIONS: The survival
      rate equalled 65% between 1953 and 1978, reached 86% between 1979 and 1989, and
      91% after the year 1990, however, it is worth mentioning that after the year 1995
      there were no fatal cases.

PMID- 21735663
TI  - [The presentation of laryngeal malignant tumors of mesenchymal origin].
AB  - Although laryngeal malignancies of mesenchymal origin (laryngeal sarcomas, LS)
      are extremely rare (1% of all laryngeal malignancies), the histological
      manifestations are very diverse. LS sign as a solid tumor covered with an intact
      mucosa. THE AIM OF THE STUDY: was to evaluate retrospective data referring:
      epidemiology, clinical manifestations, treatment and early follow-up; based on
      medical record made in ORL, HNS Surgery Dpt of Holy Cross Cancer Centre in Kielce
      during 9-years period 2001-2009. MATERIAL AND METHODS: The retrospective analysis
      of the group of 12 patients with LS was made. Studied characteristics were: age,
      sex, primary focus, histological outcome, treatment options and early follow-up.
      RESULTS: Age of the group of 12 studied patients (10 M, 2 F) ranged from 48 to 84
      (mean 69.8). LS accounted 1.2% (12/935) for all of laryngeal malignancies. The
      focus of origin were: glottis (6), epiglottis (5); subglottis (1). The most
      common histological types of LS at studied group were: neurosarcoma (2),
      fibrosarcoma (2), plasmocytoma (2), chondrosarcoma (1), malignant fibrous
      histiocytoma (1), sarcoma low grade (1), lymphoma malignum (1), liposarcoma (1)
      and haemangioendothelioma epithelioides vel plasmocytoma (1). Methods of
      treatment were: surgery (6); radiotherapy (1); chemotherapy (1); chemo- and
      radiotherapy (3); symptomatic treatment (1). The clinical results of treatment
      are: 9 patients are still alive (5 pts more than 5 years, 3 pts less than 5
      years, 1 pts less than 2.5 years with residual disease); 3 patient died: 2 pts in
      1st year from diagnosis, 1 pts after 3 years of treatment died of non-oncological
      causes. CONCLUSIONS: 1. LS are extremely rare and diversed histologically. 2.
      Immunochemical analyses are very important procedures used in diagnostics of
      these malignancies. 3. An individual approach is needed in diagnostic and
      therapeutic procedures of LS.

PMID- 21735664
TI  - [Application of botulinum toxin A in chronic intrinsic rhinitis].
AB  - Persistent, intrinsic rhinitis is common disease of heterogeneous etiology, often
      not responsive or poorly responsive to standard medical therapy. To assess the
      action of botulinum toxin type A--strong and long-acting cholinergic blocker-
      administered intranasally in the form of injection to the nasal turbinates or
      influenced Merocel to diminish the symptoms of patients reporting symptoms such
      as stuffy nose, sneezing, runny nose. MATERIAL AND METHODS: The study included 17
      patients with chronic intrinsic rhinitis. Five patients received injections of
      Botox in a dose of 10 U the lower and the middle nasal concha, ten patients are
      in the same way 20 U of Botox, two patients were applied to 40 U of Botox in the
      influenced Merocel. RESULTS: All patients had an improvement, which concerned all
      the previously reported symptoms associated with rhinitis, the full effect of the
      toxin appeared in these patients within 1-2 weeks after application and lasted,
      depending on the dose of 8-12 weeks. After this time, the effect of explicitly
      and has declined sharply, which is sometimes associated with the activity of
      natural toxins. CONCLUSIONS: Botulinum toxin type A used intranasally in
      intrinsic rhinitis is a new, effective method that allows good control of
      symptoms of the patient. The only limitation of its use is the high price of
      botulinum.

PMID- 21735665
TI  - [The prevalence of tinnitus in 7-year-old children in the eastern of Poland].
AB  - INTRODUCTION: Tinnitus in children is still rarely mentioned in medical
      literature. The prevalence of pediatric tinnitus has been reported to range
      between 3-37% and higher in children with hearing loss. OBJECTIVES: The objective
      of this study was to estimate the prevalence of the tinnitus in 7 years old
      children and to conduct statistical analysis of the relation between tinnitus and
      hearing loss. MATERIAL AND METHODS: In this study 60 212 children and their
      parents were asked about the presence of tinnitus by answering a questionnaire at
      home. Additionally, children were asked if they can hear noise in their ears or
      head, before hand hearing screening test at school was conducted. The hearing
      screening test was performed using screening audiometer with air conduction.
      RESULTS: The results showed that tinnitus was present in group of 8164 children
      (13.6%). Between children directly asked for tinnitus, 33% mentioned of having
      it. Over 75% of children did not complained of tinnitus spontaneously to parents.
      Children with hearing loss reported tinnitus twice more comparing to children
      with normal hearing. CONCLUSIONS: Tinnitus is frequent complain among 7 years old
      children. Children with hearing loss reported tinnitus twice more comparing to
      children with normal hearing. It is recommended to include to a questionnaire an
      inquiry about the presence of tinnitus during hearing screening tests performed
      recently more frequently at primary schools for early detection and diagnosis of
      tinnitus.

PMID- 21735666
TI  - [Universal electrogustometer EG-2].
AB  - Electrogustometry is a method for taste diagnosis and measurement. The EG-2
      project is being developed in cooperation between Warsaw University of Technology
      and Military institute of Medicine in Warsaw. The device is an evolution of the
      recent universal electrogustometer EG-1 prototype. Due to considerations and
      experiences acquired during prototype usage, many enhancements have been
      incorporated into device. The aim was to create an easy-to-use, portable, battery
      powered device, enabled for fast measurements. Developed electrogustometer is
      using innovative, low-power microprocessor system, which control whole device.
      User interface is based on 5.7" graphical LCD (Liquid Crystal Display) and
      touchscreen. It can be directly operated by finger or with optional stylus.
      Dedicated GUI (Graphical User Interface) offers simple, predefined measurements
      and advance settings of signal parameters. It is also possible to store
      measurements results and patients data in an internal memory. User interface is
      multilanguage. Signals for patients examinations, supplied with bipolar
      electrode, are generated by an on-board circuit using DDS (Direct-Digital
      Synthesis) and DAC (Digital-to-Analog Converter). Electrogustometer is able to
      generate DC, sinus, triangle or rectangle signals with current amplitude from 0
      to 500 pA and frequency form 0 to 500 Hz. Device is designed for manual and
      automeasurement modes. By using USB (Universal Serial Bus) port it is possible to
      retrieve data stored in internal memory and charging of built-in Li-lon battery
      as a source of power.

PMID- 21735667
TI  - [Analysis of mutations within the TP53 gene in patients with squamous cell
      carcinoma of the head and neck].
AB  - Head and neck cancer is the sixth most common type of cancer. Tobacco and alcohol
      consumption are implicated in 75% of all SCCHN and have a multiplicative combined
      effect. It is considered to be the main risk factor for the cancer development.
      The identification of a number of these genetic alterations, for example
      mutations in the p53 tumour suppressor gene, paved the way for their use as
      molecular markers. Mutations in the TP53 gene frequently occur in many cancers
      and are present in 50-60% of head and neck cancers, p53 plays a sentinel role in
      the pathways that prevent development of cancer by inducing apoptosis, DNA repair
      and cell cycle arrest in response to different types of cellular stress The aim
      of the study, was the assessment of the TP53 mutations prevalence in the head and
      neck cancer patients and it's relation with the clinical data and course of the
      disease. The material comprised of peripheral blood and tumour tissue obtained
      from 50 HNSCC patients with a primary tumour in the oral cavity, oropharynx or
      larynx, who were scheduled for surgical treatment. The mutations in TP53, were
      detected with use of PCR-SSCP technique. In total 8 patients (16%), showed TP53
      mutation in primary tumour. The significant correlation between tobacco and
      alcohol consumption and the mutation incidence has been observed. The site of the
      tumour and histopathological grading were also related to the prevalence of
      mutations, however without reaching the level of statistical significance. There
      was no correlation between mutations and the T and N stage of the disease.

PMID- 21735668
TI  - [A case of maxillary sinus carcinoma of a 24-year-old man, holistic aspects of
      care].
AB  - The aim of this study is to report a carcinoma affecting the maxillary sinus of a
      24-years old man. Malignant tumors of the nasal cavity and paranasal sinuses are
      rare and a very heterogeneous group of tumors. The most common is a squamous cell
      carcinoma. Sinonasal malignances usually present as a difficult diagnostic and
      therapeutic problem. The treatment depended on location, extension and histology
      of the tumor, clinical condition and the patient desire. It consisted of surgery,
      RT, surgery and postoperatory R, and concurrent QT and RT. The treatment should
      be assessed individually for each patient. The treatment of patients with
      paranasal neoplasms requires a multidisciplinary cooperation. High quality care
      requires the preparation of a team of professionals dedicated to their work. We
      observe generally human trends to restore well being in difficult situation.
      Patients transform the information about them or change the values system.
      Psychooncological help in this field reinforces natural mechanism of restoring
      well being, increasing positive emotions and patient's own activity.

PMID- 21735669
TI  - [Chylous leakage--rare but still dangerous complication after neck surgery].
AB  - latrogenic damage to the thoracic duct or large blood vessels in the neck lymph
      nodes, the operations carried out in the lower regions of the neck, especially
      the left, unfortunately, it happens even in experienced hands, because their
      intersection is often required for resection. It is essential to early diagnosis
      of complications, the best time yet in operation, which will help prevent many
      later, an extremely serious metabolic complications associated with loss of
      tissue fluid, such as electrolyte imbalance, hypovolaemia, hypoalbuminemia,
      hypoproteinemia, hypovolaemia, lymphopenia, immunosuppression and others, leading
      sometimes to death. AIM: To assess the incidence of cervical lymphorrhoea in
      patients who have undergone neck surgery and assessment of risk factors for this
      complication, and a review of methods of treatment. MATERIALS AND METHODS: In the
      years 2000-2009 in the Department of Otolaryngology and Laryngological Oncology
      in Poznan, among 1899 patients who underwent surgery on his neck were 7 cases of
      iatrogenic cervical lymphorrhoea, including 2 cases of chylothorax. RESULTS: In 6
      cases, intensive medical treatment during the two weeks leading to complete cure,
      in a case of a patient after radical removal of metastatic medullary thyroid
      carcinoma descending deep into the mediastinum, reoperation, and despite
      aggressive drug treatment lymphorrhoea continued, there were devastating
      metabolic effects leading to death. CONCLUSION: latrogenic fistula and lymphocele
      is a rare, dangerous and difficult to treat and potentially fatal complication of
      surgery of the neck. It should be recognized as early as possible in order to
      implement the treatment without committing to devastating metabolic effects.

PMID- 21735670
TI  - [The priest Sebastian Kneipp and his outlook on otorhinolaryngology diseases].
AB  - The silhouettes of the Priest Sebastian Kneipp, one of the pioneers of world
      hydrotherapy are presented first of all. Impressions of Polish doctors Jozef
      Surzycki and Wladyslaw Jasinski from this hydrotherapeutic institution are
      outlined. The Kneipp's hydrotherapeutic achievements in treatment of illness of
      ears, common cold, angina, diphtheria, hoarseness, vocal insufficiency are
      described in more detail.

PMID- 21735671
TI  - [Medical complications of surgical procedures in malignancies of the head and
      neck].

PMID- 21735672
TI  - [Lipid peroxidation and endogenous intoxication during hirudotherapy for
      gonarthrosis].
AB  - The time course of changes in lipid peroxidation and the characteristics of
      endogenous intoxication were studied in the treatment of patients with
      gonarthrosis. The findings suggest the positive changes in the biochemical
      parameters that characterize endogenous intoxication and recovery of the body's
      antioxidant status despite the activation of prooxidative processes.

PMID- 21735673
TI  - [Lipid peroxidation and antioxidant defense in patients with severe herpetic
      infection].
AB  - Lipid peroxidation and antioxidant defense were studied in 42 patients with
      severe herpetic infection. The higher plasma and red blood cell levels of
      intermediate (trienic conjugates) and end (Schiff's bases) lipid peroxidation
      products were revealed during remission and disease recurrences. At the same
      time, there were increases in the content of ceruloplasmin in the plasma and in
      that of superoxide dismutase and catalase in the red blood cells. In the patients
      with herpetic infection, there were different correlations between the values of
      lipid peroxidation and antioxidant defense, which were absent in the group of
      donors. There was a direct correlation between the level of oxidation of
      intermediate products (ketodienes) of neutral lipids in the plasma and the
      concentrations of ceruloplasmin and negative correlations with red blood cell
      superoxide dismutase in patients in remission. There were negative correlations
      between the red blood cell level of oxidation of intermediate phospholipid
      peroxidation products and the concentration of ceruloplasmin.

PMID- 21735674
TI  - [Relationships between the lipid metabolic parameters and the humoral factors of
      natural immunity in children and adolescents].
AB  - With age, antiatherogenic defense in North aboriginal children is regulated by
      the humoral mechanisms of immunity, by increasing the levels of immunoglobulins
      (IgG, IgA), interleukin-4, and tumor necrosis factor-a and decreasing the content
      of interleukin-8 and interferon-alpha in particular, by reflecting the ability of
      the immune system to maintain and reduce the atherogenicity of blood lipids.

PMID- 21735675
TI  - [Methodological approaches to choosing informative laboratory biomarkers and
      their complexes for the early detection of the influence of harmful factors on
      man and for the diagnosis of occupational diseases].
AB  - Methodological approaches and strategy have been developed to choose informative
      laboratory biomarkers for the early and preclinical diagnosis and to detect the
      negative influence of harmful industrial and environmental factors. The paper
      considers whether the diagnostic value of laboratory tests can be defined, by
      studying the relationship of endogenous exposure (effect) and the proportion of
      subjects with the changed level of a biomarker (response) to the dose of a
      substance, stage of disease, and length of service. Due to the polysyndromic
      pattern of many occupational diseases, it is shown to be most expedient to carry
      out a few tests characterizing different aspects of the pathogenesis of disease.
      Methodological approaches to developing a set of informative biomarkers have been
      proposed.

PMID- 21735676
TI  - [Investigation of platelets by the flow cytofluorometric technique (a review of
      literature). Part 2].
AB  - The paper reviews literature updates on the examination of platelets by the flow
      cytofluorometric technique; it analyzes in detail the effect of various
      anticoagulants used to stabilize blood, the time and conditions of sample storage
      at the preanalytical stage of studies on the results of an analysis. Different
      platelet subpopulations detected by the flow cytofluorometric technique are
      described and their clinical value is shown. The clinical importance of reticular
      platelet tests is separately considered. This technique is acknowledged to be
      currently of urgency in estimation of platelets.

PMID- 21735677
TI  - [Assessment of thromboplastins according to the WHO guidelines and the results of
      external quality control].
AB  - The study was undertaken to assess commercial thromboplastins for compliance to
      the WHO guidelines and to substantiate the validity of the results of a
      prothrombin test carried out using these thromboplastins. The test
      thromboplastins were shown to meet the WHO guidelines for assessment of
      thromboplastins. Over 5-8 years of the authors'participation in two external
      quality control programs (Federal External Quality Control System, Russia; 72
      trials; NEQAS, United Kingdom; 60 trials), the international normalized ratio
      derived through the use of assessed thromboplastins did not differ from that
      established due to the interlaboratory consensus value of both external quality
      control systems. It is concluded that correct thromboplastin assessment provide
      accurate results of determination of prothrombin time.

PMID- 21735678
TI  - [The platelet hemostatic system and prooxidant and antioxidant potentials in the
      dynamics of burn disease].
AB  - Platelet aggregation and prooxidant and antioxidant potentials were studied in
      patients with burn more than 20% total body surface area for 30 days after
      injury. There were progressive increases in platelet aggregation, lipid
      peroxidation, and antioxidant activity. The possible pathogenetic aspects of the
      findings are discussed.

PMID- 21735679
TI  - [The preanalytical stage of studying the hemostatic system].
AB  - The efficiency of applying precision devices and multiple laboratory methods
      devised to reveal the causes of bleeding and thromboses significantly depends on
      whether a wide range of rules of the preanalytical stage of the study is
      observed. The paper gives detailed information on conditions for taking blood
      samples, their transport, and preparation for examination of the hemostatic
      system. The given information is based on the worldwide recommendations and many
      years' experience gained by the authors at the laboratory of hemostasis.

PMID- 21735680
TI  - [Experimental quality assessment of APTT-control reagent kits in the study of
      heparin-containing plasma in therapeutic ranges].
AB  - Investigation of activated partial thromboplastin time (APTT) in the plasma
      samples containing different levels of heparin determines the following
      parameters of the quality of APTT-control reagent kits: coefficient of variation,
      linearity, sensitivity, and detection. The kit is shown to meet GOST P 51352-99
      requirements. The determination of the validity coefficient of approximation has
      proven a directly proportional functional relationship of the APTT values to the
      level of heparin in therapeutic ranges in the logarithmic coordinate system. The
      kit may be used to monitor heparin therapy.

PMID- 21735681
TI  - [Peripheral blood neutrophil subpopulations and capacities of NBT test in the
      diagnosis of neonatal diseases].
AB  - By analyzing the data available in the literature, the author shows new
      capacities of the nitroblue tetrazolium (NBT) test in the diagnosis of neonatal
      diseases and conditions. The findings versus the, data obtained in adult patients
      are characterized. The NBT test has been used to determine changes in neutrophil
      subpopulations. The kinetic parameters of the process are analyzed.

PMID- 21735682
TI  - [New nutrient medium for the cultivation and isolation of the plague microbe ChDS
      37 as an element of the mobilization reserve of specialized antiepidemic teams of
      the Russian Inspectorate for the Protection of Consumer Rights and Human
      Welfare].
AB  - A new nutrient medium has been designed to culture and isolate the plague microbe
      ChDS-37 on the basis of the pancreatic digest of baker's yeast. The results of
      laboratory tests of the designed medium, by using 10 plague microbe strains and
      those of approval during the tactical and special training of a specialized
      antiepidemic team (SAET), suggest that the medium has some advantage over
      reference media and creates prerequisites for being incorporated into the
      mobilization reserve of a SAET.

PMID- 21735683
TI  - [Comparison of two phenotypic methods for detecting the production of extended
      spectrum beta-lactamases by hospital Klebsiella pneumoniae strains].
AB  - In the period 2006-2008, the Republican Emergence Medical Care Center.isolated
      2997 enterobacteria, 48.9% of which belonged to Klebsiella pneumoniae. Confirming
      phenotypic methods, such as double disk method (DDM) and double disk synergy test
      (DDST), were used to examine 64 K. pneumoniae strains that had been regarded as
      being suspected to produce extended-spectrum beta-lactamases (ESBL) during a
      preliminary screening. Of the 64 K. pneumoniae strains, 6 (9.4%) were
      unsusceptible to clavulanate and not referred to as ESBL producers and 5 (7.8%)
      were resistant to imipenem. DDM ranks below DDST as it (concurrently with DDST)
      yielded positive results only in 30 (51.7%) strains; 28 (48.3%) cultures were
      positive only with DDST - these strains were significantly more frequently
      resistant to three third-generation test cephalosporins during primary screening.

PMID- 21735684
TI  - [On international experience in standardizing clinical laboratory studies].
AB  - The paper gives the main points of a reference system for laboratory medicine. It
      describes the possibilities of using reference methods and certified reference
      materials for the standardization of methods to measure the catalytic activity of
      enzymes and those to evaluate thyroid function.

PMID- 21735685
TI  - [Doppler blood flow velocimetry in the middle cerebral artery in uncomplicated
      pregnancy].
AB  - OBJECTIVE: To determine the resistance index (RI) and pulsatility (PI) in the
      middle cerebral artery (MCA) in prediction of abnormal fetal heart rate during
      labor and poor fetal outcome in term pregnancy. MATERIAL AND METHODS: The study
      included 148 patients at term in uncomplicated pregnancy Daily evaluation of
      blood flow in the MCA was performed and PI and RI were calculated. The last value
      before delivery was taken for the analysis. The predictive value of Doppler
      parameters has been determined in turn to predict abnormal FHR during labor and
      abnormal newborn condition. Evaluation included fetal CTG parameters and newborn
      status based on the V Apgar scale and acid-base equilibrium in the umbilical cord
      blood. Then selected parameters, characterizing pregnancy and the newborn status,
      were compared with abnormal Doppler results. The prognostic value of Doppler
      indices was assessed for selected parameters determining the course of pregnancy
      and abnormal fetal heart rate. RESULTS: Poor predictive value of UA PI and RI in
      the prediction of abnormal fetal heart rate during labor and poor fetal outcome
      was found. The RI in the UA presented the highest predictive value. CONCLUSION:
      PI in the MCA shows higher predictive value than RI in the detection of abnormal
      fetal outcome and abnormal fetal heart rate in uncomplicated pregnancy at term.
      However PI indices, particularly RI in the middle cerebral artery have low
      predictive value for the analyzed parameters.

PMID- 21735686
TI  - [Increased oxidized LDL cholesterol levels in peritoneal fluid of women with
      advanced-stage endometriosis].
AB  - INTRODUCTION: Proinflammatory and prooxidative environment in the peritoneal
      cavity may be involved in the pathogenesis of endometriosis. Imbalance between
      reactive oxygen species levels and the antioxidant capacity leads to oxidation of
      low-density lipoproteins (LDL). The importance of oxidized LDL (Ox-LDL) in the
      development of atherosclerosis is well recognized. AIM: The aim of our study was
      to evaluate for the presence of ox-LDL in the peritoneal fluid (PF) of women with
      and without endometriosis. MATERIAL AND METHODS: A total of 60 women who
      underwent laparoscopy were divided into groups: endometriosis sufferers with
      minimal to mild (n 20) and moderate to severe (n 20) stages, and the reference
      group (n 20) with functional follicle ovarian cysts. Oxidized LDL levels were
      determined in the PF using enzyme immunoassay RESULTS: Oxidized LDL levels were
      detectable in all peritoneal fluid samples. Significantly increased levels of ox
      LDL were observed in PF of women with stage III/IV endometriosis compared to the
      reference group (p = 0.03). However peritoneal fluid ox-LDL concentrations did
      not differ significantly between patients with minimal/mild and women with
      moderate/severe stage of the disease (p = 0.2). No significant difference in the
      PF ox-LDL concentrations was also found between women with stage I/II
      endometriosis and patients with follicle cysts (p = 0.3). CONCLUSIONS: Increased
      peritoneal fluid ox-LDL levels observed in women with advanced-stage
      endometriosis suggest the important role of oxidative stress in the pathogenesis
      of the disease.

PMID- 21735687
TI  - [Antitumor effects of sulindac in ovarian cell cultures].
AB  - OBJECTIVE: The purpose of our study was to assess susceptibility of cells of
      various ovarian cell lines on different nonsteroidal anti-inflammatory drugs
      (NSAIDs). MATERIALS AND METHODS: Cytotoxic effect of NSAIDs was tested using MTT
      colorimetric assay. RESULTS: Amongst 6 NSAIDs tested: sulindac, sulindac sulfide,
      sulindac sulfone, acetylsalicylic acid, nimesulide, and rofecoxib, viability of
      ovarian carcinoma cells was compromised most strongly by sulindac and sulindac
      sulfide and concerned all the cell lines tested: SKOV-3, MDAH 2774, OVCA-1, and
      OVP-10. Sulindac sulfone and rofecoxib also displayed some cytotoxic effect
      during prolonged 72-hour incubation. Other NSAIDs tested: nimesulide and
      acetylsalicylic acid were devoid of cytotoxic effect on ovarian cancer cells.
      CONCLUSION: Our results are encourage enough to conduct clinical trials that
      could allow to draw conclusions regarding potential application of sulindac in
      the adjuvant treatment of a standard chemotherapy of ovarian cancer.

PMID- 21735688
TI  - [Influence of estradiol administration mode on plasma insulin-like growth factor
      I (IGF-I) and its binding proteins 1 and 3 concentration in postmenopausal women
      treated with norethisterone acetate].
AB  - AIM: The aim of the present work was to assess the influence of estradiol
      administration mode on the plasma IGF-I, IGFBP-1, IGFBP-3 levels in
      postmenopausal women treated with norethisterone acetate. MATERIAL AND METHODS:
      39 women were enrolled into the study Group A--14 women received transdermal
      17beta-estradiol (Oesclim 50--Fournier-Solvay) combined with oral norethisterone
      2.5 mg daily (Primolut-Nor--Schering), Group B--10 women on oral 2 mg 17beta
      estradiol combined with oral 1 mg daily norethisterone (Kliogest--Novo-Nordisk).
      Control group (group C) consisted of 15 postmenopausal women who received no
      treatment. Basic plasma FSH, estradiol and total IGF-I, IGFBP-1 as well as IGFBP
      3 levels were measured initially and at the 52nd week of the study. RESULTS: The
      mean plasma FSH level was reduced and mean plasma estradiol level was increased
      in groups A and B during hormone therapy. Mean plasma levels of total IGF-I,
      IGFBP-1, IGFBP-3 as well as IGFBP-3/IGF-I ratio did not changed significantly
      during 52 weeks of observation in groups A, B and C. The comparison of plasma IGF
      I, IGFBP-1, IGFBP-3 between groups at the initial visit and after 52 weeks showed
      the lowest concentration f IGBP-3 in group B. Other parameters showed no
      differences among the three groups. CONCLUSION: Mode of administration of
      estradiol did not influenced the plasma levels of IGF-I, IGFBP-1, IGFBP-3 in
      postmenopausal women treated with norethisterone acetate.

PMID- 21735689
TI  - [Anti-Mullerian hormone and fertility disturbances in obese women and women with
      polycystic ovary syndrome].
AB  - Anti-Mullerian hormone (AMH) belongs to a family of growth and differentiation
      factors beta (TGF-beta). In male fetuses AMH induces regression of Muller's ducts
      whereas in female ones this hormone plays an important role during adolescence
      and reproductive period. AMH participates in regulation of folliculogenesis by
      inhibiting the recruitment of prenatal and antral follicles. The aim of the
      present study was to summarize the current knowledge of the role of AMH in
      menstrual and fertility disturbances in obese women and those with polycystic
      ovary syndrome.

PMID- 21735691
TI  - [Hereditary ovarian cancer. The role of BRCA1 gene dysfunction in response to
      chemotherapy].
AB  - Hereditary ovarian cancer is often believed to be as a distinct disease. It is
      diagnosed earlier than its sporadic type; serous subtypes and more advanced
      stages are usually observed. Mutations of genes like BRCA1, BRCA2, MMR (MLH1,
      MSH2, PMS1, PMS2) are strictly associated with the heredity of ovarian and also
      breast cancer. Systematic controls and specific procedures to lower the risk of
      those tumors are required for mutation carriers. Most authors emphasize better
      prognosis for patients with inherited type of ovarian cancer when comparing to
      sporadic one. It probably results from dysfunction of BRCA1 gene, inducing better
      response to platinum-based cytostatic drugs. This phenomenon, called "BRCAness
      profile", is also observed in non-hereditary ovarian cancers and it arises from
      somatic mutation or hypermetylation of BRCA1 promoter. Thus, the process of DNA
      repair is defective. Currently new groups of drugs using the BRCA1 dysfunctions
      are being introduced into clinical practice.

PMID- 21735690
TI  - [Bladder pain syndrome--an urological-gynecological problem].
AB  - Bladder Pain Syndrome remains a great challenge for urologists, both in
      diagnostics and treatment. Etiopathogenesis of the disease is unknown. It is
      reported that the reason for Bladder Pain Syndrome is the urothelium dysfunction
      resulting in the destruction of the protective glycosaminoglycan layer/barrier
      protecting the urothelium from bacteria adhesion and penetration of toxic
      substances/by bacteria. It is considered to be a syndrome of dysuria and
      diuresis. Urine analysis usually is normal. It is diagnosed after exclusion of
      other causes leading to painful symptoms. It is estimated that 90% of the cases
      of the disease concern women. Treatment with glycocorticosteroids, antihistaminic
      drugs and antiallergic drugs was not successful. The attempts to find the right
      method of treatment led to the introduction of hyaluronic acid, which alleviated
      Bladder Pain Syndrome and its symptoms. Hyaluronic acid reacting with
      glycosaminoglycans on the bladder decreases penetrability of irritant substances.
      The patients were treated with 4-8 weekly instillations--40 mg of hyaluronic acid
      in 50 ml NaCl solution for 1-2 months. After the last instillation, therapy is
      repeated for the next 6-8 months with one instillation monthly. This method is
      for patients a chance for getting rid of painful symptoms from the bladder

PMID- 21735692
TI  - [Position of Experts Panel of the Polish Gynecological Society in the application
      of low molecular weight heparin - nadroparin calcium (Fraxiparine) in obstetrics
      and gynecology].

PMID- 21735693
TI  - [Effects of metformin therapy on markers of coagulation disorders in
      hyperinsulinemic women with polycystic ovary syndrome].
AB  - OBJECTIVES: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism
      and oligo-/anovulation and is associated with risk factors for cardiovascular
      disorders, such as insulin resistance and central adiposity. All these factors
      can lead to endothelial dysfunction and impaired coagulation processes. Metformin
      effectively treats hyperinsulinemia in women with PCOS. However, clinical trials
      assessing influence of metformin on endothelium and fibrinolysis are limited.
      Therefore, the objective of this study was to prospectively assess the effects of
      a 6-month metformin therapy on body mass index (BMI), insulin sensitivity and
      coagulation/fibrinolysis markers in hyperinsulinemic women with PCOS. MATERIALS
      AND METHODS: Thirty hyperinsulinemic PCOS women (aged 26.0 +/- 3.7 [mean +/- SD])
      without any additional disorders were included into the study. Metformin was
      administered at a dose of 1700 mg daily for 6 months. Serum plasminogen activator
      inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) concentrations
      and von Willebrand factor (vWf) levels were measured with specific assays,
      together with glucose and insulin concentrations. Insulin sensitivity index (ISI)
      and BMI were calculated. RESULTS: All patients completed the study and no side
      effects were reported. BMI decreased significantly (by 8.5%, p < 0.0001). The
      metformin therapy improved insulin sensitivity as evidenced by an increase in ISI
      by 41.5% (p = 0.0005). A marked reduction in PAI-1 (by 26%, p < 0.005)
      concentrations was observed. No significant changes were noted for t-PA and vWf.
      CONCLUSIONS: Metformin administration decreases the circulating PAI-1
      concentration and simultaneously improves insulin sensitivity and BMI in PCOS
      women with hyperinsulinemia. Long-term metformin administration may be a new
      prophylactic measure for the prevention of cardiovascular disorders in such
      patients.

PMID- 21735694
TI  - [The management of ovarian tumors in pregnancy and perinatal outcome].
AB  - AIM: The pregnancy course in women with gestational ovarian mass and conservative
      or operative management. MATERIAL AND METHODS: In retrospective analysis we
      analyzed 83 pregnant women with ovarian mass diagnosed between 2002-2009. We
      considered the following factors: gestational age when diagnosed, ultrasound
      picture, clinical symptoms, level of CA 125, treatment used, pathologic results
      and pregnancy outcome. RESULTS: In this group of patients 29 (35%) underwent
      surgery and 54 (65%) were managed conservatively In 83% of operated women ovarian
      mass was diagnosed before 11 gestational week. Only 27.5% of patients had pain.
      CA 125 level was elevated in 48.3% women. In all operated patients laparotomy was
      performed. The most common pathologic finding was mature teratoma (37.9%) and
      serous cyst (34.5%). In only one patient we diagnosed borderline serous carcinoma
      in both ovaries. Among operated patients, 86% delivered at term healthy newborns.
      In conservatively managed group level of CA 125 remain within a normal range.
      Patients were symptoms free and pregnancy course was uneventful. In 85% non
      operated women within 6 postpartum weeks ovarian masses disappeared. CONCLUSION:
      According to our analysis adequate ultrasound image interpretation of ovarian'
      tumors in pregnancy is of the highest importance in further medical management.
      Conservative treatment with systematic obstetric care may help to reduce the
      number of surgical intervention. Surgical treatment of ovarian tumors in
      pregnancy increases the risk of premature deliveries.

PMID- 21735695
TI  - [Disturbance of gene expression in endometrial cancer as therapy aim].
AB  - Endometrial carcinoma is the most common gynecological cancer in women in
      developed countries. Two types of endometrial cancer, type I (estrogen-related)
      and type II (estrogen-unrelated), may be distinguished on the basis of molecular
      and clinicopathological characteristics. The article presents the most common
      mutations leading to the development of endometrial carcinomas such as PTEN
      (Phosphatase and Tensin Homolog), overexpression of COX-2 gene, VEGF (Vascular
      Endothelial Growth Factor), ErbB-2 (HER2) proto-oncogene. Also, new strategies of
      treatment of this disease, based on directed drugs with specific mechanism of
      drug action, have been described. Those drugs offer considerable hope in treating
      advanced stages of metastatic cancers, particularly combined with chemotherapy.
      Knowledge of pathomechanisms of endometrial cancer together with proper selection
      of patients, proceeded by tests which determine changes of gene expressions, may
      significantly improve the efficiency of the treatment. The authors present
      available publications on the subject of clinical research regarding new drugs
      used in monotherapy and combined therapy of endometrial carcinoma.

PMID- 21735696
TI  - [Precocious puberty].
AB  - Precocious puberty is an early sexual maturation before the age of 8 in case of
      girls and 9 in boys. There are two types: isosexual precocious puberty-
      characteristic are appropriate for the child's genetic and gonadal sex; and
      heterosexual precocious puberty--sexual characteristic are inappropriate for the
      genetic sex (feminizing syndrome in boys or virilizing syndrome in girls).
      Precocious puberty is an important problem in childhood gynecology pediatrics,
      endocrinology and psychology.

PMID- 21735697
TI  - [Pregnancy and possible complications in a patient with Sjogren's syndrome--a
      case report].
AB  - This article presents a case of a 29-year-old pregnant woman with Sjogren's
      syndrome, regardless of her first pregnancy loss, conceived and delivered a
      healthy baby. The authors have also reviewed available medical literature and
      have indicated problems that typically occur in such patients. Diagnostic
      methods, therapeutic possibilities, and common complications that obstetrician
      have to deal with while taking care of pregnant women with Sjogren's syndrome
      have been shown.

PMID- 21735698
TI  - [A case of antiphospholipid syndrome in course of pregnancy and puerperium with
      lupus-like disease suspicion].
AB  - The antiphospholipid syndrome (APS) is a systemic non-inflammatory and autoimmune
      connective tissue disease. ASP is characterized by formation of autoantibodies
      against cell membrane phospholipids which act as procaogulation factors.
      Association with recurrent pregnancy loss, intrauterine growth retardation,
      preeclampsia and placenta ablation makes ASP a serious perinatologic problem. The
      primary form can evaluate into lupus-like disease or full-symptomatic lupus
      erythematosus, both usually preceded by acute form of APS. In pregnant women this
      situation may present considerable diagnostic problems. The aim of this work was
      to present a patient with acute primary antiphospholipid syndrome during
      pregnancy and puerperium, which subsequently was diagnosed as systemic lupus
      erythematosus flare. Such progression is rare and, despite several previous
      reports, requires extensive explanations and research.

PMID- 21735699
TI  - [Intrauterine blood transfusion in case of placental chorangioma].
AB  - The paper presents a case of placental tumor causing hemodynamic changes. Doppler
      studies and fetal echocardiography allowed the diagnosis of hyperkinetic
      circulation in the course of fetal anemia. Cordocentesis has been performed and
      confirmed fetal anemia. The treatment used, intrauterine blood transfusion,
      allowed the compensation of hemodynamic and hematological disorders. Paper
      presents a detailed diagnostic and therapeutic procedures in the event
      chorangioma in pregnancy.

PMID- 21735700
TI  - [Letter to the Editor. Supplementing the work of views "fetal tachyarrhythmia -
      the current state of knowledge"].

PMID- 21735701
TI  - [Official Polish Gynecological Society Expert Panel position on reasons for
      hormonal contraceptive failure].

PMID- 21735702
TI  - [The role of peroxisome proliferator activated receptors in metabolic balance
      disturbances under stress].
AB  - Some aspects of peroxisome proliferator activated receptors (PPAR) involvement in
      regulation of stress-dependent biological processes leading to insulin
      resistance, lipid imbalance, hypertension and inflammation are reviewed. Analysis
      of literature data clearly shows the main role of PPAR in stress signal
      transduction following to metabolic disbalance development under prolonged stress
      conditions. The interplay of three PPAR isoforms functional activity with
      metabolic process disturbances during stress is under special emphasis. Taking
      into account experimental data described in literature we suggest that PPAR
      activation under acute stress is an adaptive response while stable PPAR
      hyperexpression under prolonged stress can cause insulin resistance,
      hypertension, and visceral obesity. The strategy of PPAR using as pharmacological
      targets in metabolic syndrome correction is under consideration.

PMID- 21735703
TI  - [Historical sketches on classical physiology of the heart: the initial phase of
      systole].
AB  - Crucial physiological advances in the phase analysis of cardiac performance with
      respect to their historical and biographical aspects are elucidated. The
      described period started from the early measurement of blood pressure (1733) and
      the first graphical representation of cardiac performance (1861), continued by
      the progress in recording of cardiac electrical activity and a detailed study of
      the consecutive events throughout the cardiac cycle (1921) and, finally, reached
      the recording of changes in the left ventricular dimensions and shape during the
      phase which precedes the start of blood ejection (1955-2005).

PMID- 21735704
TI  - [A possible mechanism of participation of neuronal loops cortex - basal ganglia -
      thalamus - cortex in time perception].
AB  - A mechanism of time perception is suggested. It is based on a postulate that time
      when stimulus arrives (parameter "when") is such property of stimulus as its
      physical properties (parameters "what"), and association "what - when" is
      perceived in those area of neocortex in which property "what" is processed after
      its repeated excitation. The time of repeated excitation which determines clock
      rate of "intrinsic clock", depends on dopamine influence at functioning of the
      cortico - basal ganglia - thalamocortical loop that promotes contrasted
      amplification of activity of cortical neurones, firstly activated by stimulus.
      Accumulation of time counts is performed in the neocortex and coded by the number
      of neuronal discharges. Duration of current interval is proportional to the
      number and duration of cycles of repeated neocortical excitation. Time counting
      can be started involuntary by stimulus, or voluntary due to activation of
      prefrontal cortex. The mechanism of time perception is similar for stimuli of
      different modalities owing to resemblance of functioning of topically organised
      cortico - basal ganglia - thalamocortical loops, it follows from our model that
      the more (less) concentration of dopamine in the striatumm the higher (low) clock
      rate, so the real interval will be estimated more (less) precisely and perceived
      as longer (short). These consequences of the model are in accordance with known
      experimental data.

PMID- 21735705
TI  - [Psychophysiological indexes of recognition of emotions in speech].
AB  - A review of experimental and theoretical works upon perception of emotions in
      speech is introduced. The main approaches to experimental study and different
      types of stimulation are considered. Clinical research and experiments upon
      healthy subjects investigate the brain organization of emotional speech
      recognition. In the works by Rusalova, Kislova integral psychophysiological
      preconditions for the successfulness of the recognition of speech emotional
      expression were studied. As a result of the investigation, extreme groups of
      persons were identified: with high indices of "emotional hearing" and with low
      level of recognition of emotions. Analysis of EEG included comparison of
      different EEG parameters between two groups: values of EEG power, the dominating
      frequencies, percentage of different EEG-bands in the summary EEG power,
      coherence, values of EEG inter- and intra-hemispheric asymmetry, etc. The
      subjects with low identification rates showed a higher brain activation and
      reactivity both during the emotion identification task and at rest as compared to
      the subjects with high identification rates. The data obtained reveal specific
      activation within the left frontal regions, as well as the right posterior
      temporal cortex during nonverbal recognition of emotions.

PMID- 21735706
TI  - [Biological role and functional characteristics of calcitonin in human and animal
      organisms].
AB  - In the review the literary data on the subject of biological role and functional
      characteristics of calcitonin in human and animal organisms are demonstrated. The
      own results concerning the study of local exposure of calcitonin of salmon
      (preparation "Miacalcic") on the development of inflammatory destructive
      processes in articular structures of the affected knee joints in rabbits with
      experimental rheumatoid arthritis are briefly designated.

PMID- 21735707
TI  - [Concept problem "the functional condition" in modern physiology].
AB  - The concept "functional state" is discussing with attraction notion about
      fundamental components of live organism: substance, structure, production of
      energy and information, entropy. In the specified terms is giving working
      definition of functional condition. From such of positions the normal functional
      state, and its making--physiological state and psychological state, is
      considered.

PMID- 21735708
TI  - [Expert reconstruction of the true circumstances of the shooting of the Emperor
      Nikolai II, members of his family, and those who accompanied them into exile at
      Ekaterinburg].
AB  - Analysis of the materials of the criminal case, historical, archive, and forensic
      medical documents permitted for the first time to reconstruct the circumstances
      of the shooting of Emperor Nikolai II, members of the royal family, and those who
      chose to accompany them into exile in the house of the engineer N.N. Ipatiev,
      Ekaterinburg, on the night of 16-17th July (Grigorian calendar) 1918. The results
      of the study allowed the true picture of the assassination to be reconstructed
      including the mutual positions of the victims and the executors in the semi
      basement room No 2, the total number of participants, the number and direction of
      shots, the types of the weapons used, and the sequence of actions of each person
      involved in the event. It was shown, that in the beginning most shots had been
      fired at the emperor and tsarevich Alexei.

PMID- 21735709
TI  - [Peculiarities of combined blunt head injuries in children and adolescents].
AB  - The objective of the present study was to evaluate the frequency and peculiar
      features of combined head injuries in children and adolescents who suffered the
      fatal blunt trauma. A total of 101 corpses and 188 archive records were available
      for the analysis. The control data group was comprised of 227 original
      observations of adult corpses. It was shown that head injuries prevail over
      injuries to other parts of the body in children with combined blunt traumas. The
      craniocerebral injuries are more frequent in children and adolescents than in
      adult subjects but their extent is smaller. Fractures of the facial bone skeleton
      in adults occur twice as frequently as in children. A peculiar feature of
      craniocerebral injuries in children and adolescents is incomplete splintered
      fractures and folded deformation of the bone plate. Subarachnoidal hemorrhage
      occurs equally frequently in children and adults with craniocerebral injuries.
      Other intracranial manifestations of the injury, such as ruptured brain tunics,
      epidural and subdural hemorrhage, cerebral contusion and ventricular hemorrhage
      in children occur less frequently than in adults.

PMID- 21735710
TI  - [Forensic medical characteristics of stab wounds caused by objects differing in
      the blade sharpness].
AB  - Based on the results of the present experimental study, morphological and
      histological criteria for incised skin wounds from objects differing in the blade
      sharpness were developed.

PMID- 21735711
TI  - [Qualitative histological diagnostics of the remoteness of traumatic subdural
      hematomas].
AB  - The present histological study was based on the examination of dura mater,
      capsules, and contents of 200 subdural hematomas (SDH) obtained from the corpses
      of subjects with a non-penetrating craniocerebral injury within a period from 1
      hour to 2.5 years after the trauma. A total of 14 well-reproducible qualitative
      morphological criteria have been identified for diagnostics of the prescription
      of subdural hematomas; the probability and the exact earliest and latest times of
      their manifestation at different dates of the posttraumatic period were
      calculated. Sensitivity, specificity, and prognostic value of the proposed
      qualitative morphological criteria for the prescription of traumatic subdural
      hematomas were evaluated. The results of the study can be used in the practical
      work of forensic medical experts.

PMID- 21735712
TI  - [Forensic medical expertise of injuries in the anorectal region and rectum
      related to the sexual assault].
AB  - Injuries to the anorectal region and rectum associated with sexual crimes require
      forensic medical assessment even though this issue remains to be poorly
      developed. The results of 84 forensic medical expertises are presented based on
      the materials obtained by examining both women and men who applied with complains
      of sexual abuse (anogenital penetration) to the Primorskoye territorial Bureau of
      forensic medical expertise during 5 years, from 2005 to 2009. The study has
      demonstrated correlation between dynamics of applications of the victims of
      either sex and the lack of a tendency toward a decrease in their frequency. The
      signs characteristic of acute injuries and chronic conditions are described. The
      causes of diagnostic errors during forensic medical expertise of sexual abuse are
      discussed.

PMID- 21735713
TI  - [The methodological basis for the expert assessment of unfavourable outcomes of
      the treatment].
AB  - Procedures of forensic medical examination are considered with special reference
      to the cases of unfavourable outcomes of the treatment and methodological basis
      of their expert assessment. The step-by-step analysis of the doctor's actions is
      proposed for their objective evaluation. The objective opinion of the expert
      commission should be based on the medical criteria for the doctor's actions.

PMID- 21735714
TI  - [Optimization of the biological microchip for genotyping the AB0 locus:
      analytical aspects].
AB  - The present work continues the search for methodological options facilitating the
      improvement and optimization of the biological microchip designed for genotyping
      the AB0 locus. It was shown in an earlier study designed to test a prototype
      biological microchip using a reference set of preparations with the known group
      specificity that under certain conditions some cells of the biochip appear to
      generate artifact hybridization signals that tend to make the results of
      genotyping either incorrect or difficult to interpret. We performed the
      correction of the molecular structure of DNA probes of the prototype biochip for
      the purpose of optimization of their hybridization potency. In addition, we
      developed and synthesized new DNA probes and designed new variants of the
      biochip. The experimental analysis of hybridization properties of all DNA probes
      thus obtained was carried out for the final choice of the most promising options
      suitable for the creation of the optimized biochip.

PMID- 21735715
TI  - [The development of a test-system for the quantitative and qualitative evaluation
      of DNA content in criminalistic objects by the real-time polymerase chain
      reaction].
AB  - An original test-system for the preliminary quantitative and qualitative
      evaluation of isolated DNA is proposed by the polymerase chain reaction in real
      time (PCR-RT) based on the TaqMan technology. This test-system permits to
      simultaneously measure the amount of DNA in the sample, identify the genetic
      gender, and detect PCR inhibitors. The method has been approbated in the
      practical work of forensic medical experts.

PMID- 21735716
TI  - [The comparative assessment of the practical value of the currently employed
      methods for the recognition and species specificity of the blood].
AB  - The objective of the present study was to evaluate sensitivity and specificity of
      the HemDirect method on test-plates (Seratec) for detecting human hemoglobin
      (HHb). These characteristics were compared with those of other widely used
      methods designed for the detection of blood traces, viz. thin layer
      chromatography, hemotest, spectrofluorimetry, and identification of blood species
      specificity (by countercurrent immunoelectrophoresis in agar and on the acetate
      cellulose film). It was shown that the HemDirect test is highly specific and far
      more sensitive than other techniques used for the same purpose in the practical
      work. It can be recommended as the method of choice for the detection of blood
      microtraces.

PMID- 21735717
TI  - [Correction of the alkylnitrite method for the measurement of ethanol in blood:
      direct experimental evidence].
AB  - A coefficient (multiplier) for the correction of a systemic inaccuracy of ethanol
      detection in the blood by the alkylnitrite method arising from calibration
      against an aqueous solution has been improved. The experiment was carried out as
      a multilaboratory study (with the participation of six laboratories). The value
      of the coefficient was estimated at 0.82 +/- 0.014 (SD) instead of 0.95 computed
      earlier (CV = 1.7%). The main factor influencing the value of the coefficient
      turned out to be the time of preparation of the model ethanol-blood mixture for
      comparison with the aqueous solution. The coefficient of 0.82 was obtained using
      fresh blood samples that of 0.93 to 0.96 with blood samples previously stored
      during 3-10 days. The results of the study suggest different ethanol distribution
      patterns in vivo and in vitro in the aqueous phase of the blood stored for a few
      days.

PMID- 21735718
TI  - [Extraction of lambda-cyhalothrin from aqueous dioxan solutions].
AB  - The results of extraction of lambda-cigalotrin from dioxan aqueous solutions by
      hydrophobic organic solvents are presented. It is shown that the degree of
      extraction depends on the nature of the extractant, the water to dioxan ratio,
      and saturation of the water-dioxan layer with the electrolyte. The highest
      efficiency of lambda-cigalotrin extraction was achieved using chlorophorm as a
      solvent under desalination conditions. The extraction factor was calculated
      necessary to obtain the desired amount of lambda-cigalotrin from the water-dioxan
      solution (4:1) with the help of the extractants being used.

PMID- 21735719
TI  - [The method for the qualitative assessment of certain characteristics of the
      bullet trajectory in case of the extremity gunshot wounds].
AB  - A method for the qualitative assessment of certain characteristics of the bullet
      trajectory in the case of a gunshot wound to an extremity is proposed to be used
      for the mathematical simulation of the mechanism of formation of such injuries.

PMID- 21735720
TI  - [The propriety of establishing the fact of neonatality based on the examination
      of the child's corpse].
AB  - It is shown based on the historical and legal analysis that the designation of
      the child's status as a newborn infant throughout the period of its neonatal life
      till violent death "at or immediately after births" is the exclusive prerogative
      of the law-enforcement authorities. An original approach has been developed and
      recommended for the introduction into the expert practice. According to this
      proposal facts and arguments in the "Expert conclusions" should be formulated so
      as to avoid mentioning the child as newborn and to indicate only the duration of
      its extrauterine life. Such an approach leaves it to the law-enforcement
      authorities to decide in each concrete case whether the child should be
      designated as a newborn infant or not.

PMID- 21735721
TI  - [The effects of attention to body sensations and muscular relaxation on mood and
      decentering].
AB  - Mechanisms of Dohsa-hou (a holistic psycho-rehabilitation method) were
      investigated by comparing the effects of attention to body sensation and muscular
      relaxation. Participants were randomly divided into the following three groups.
      The Dohsa + Attention (D + A) group practiced Dohsa-hou by focusing attention on
      somatic sensations. The Dohsa (D) group practiced Dohsa without focusing
      attention. The control group did not practice Dohsa. All the participants were
      assessed using the Decentering Scale, the Self-Acceptance Scale, and the
      Depression and Anxiety Mood Scale before and after the intervention. The results
      indicated that both the D + A and D groups had increased self-acceptance and
      decreased anxiety scores. However, in comparison to the control group, the
      decentering score increased in the D + A group (p < .05), whereas the Depression
      score decreased in the D group (p < .05). These findings suggest that attention
      to body sensations is effective in increasing decentering, whereas muscular
      relaxation is effective in decreasing depressed mood.

PMID- 21735722
TI  - [The relationship of empathic-affective responses toward others' positive affect
      with prosocial behaviors and aggressive behaviors].
AB  - The purposes of this study were to develop and validate the Empathic-Affective
      Response Scale, and to examine the relationship of empathic-affective responses
      with prosocial behaviors and aggressive behaviors. Undergraduate students (N =
      443) participated in a questionnaire study. The results of factor analysis
      indicated that empathic-affective responses involved three factors: (a) sharing
      and good feeling toward others' positive affect, (b) sharing of negative affect
      and (c) sympathy toward others' negative affect. Correlations with other empathy
      related scales and internal consistency suggested that this scale has
      satisfactory validity and reliability. Cluster analysis revealed that
      participants were clustered into four groups: high-empathic group, low-empathic
      group, insufficient positive affective response group and insufficient negative
      affective response group. Additional analysis showed the frequency of prosocial
      behaviors in high-empathic group was highest in all groups. On the other hand,
      the frequency of aggressive behaviors in both insufficient positive affective
      response group and low-empathic group were higher than others' groups. The
      results indicated that empathic-affective responses toward positive affect are
      also very important to predict prosocial behaviors and aggressive behaviors.

PMID- 21735723
TI  - [A test of the focusing hypothesis for category judgment: an explanation using
      the mental-box model].
AB  - This paper presents a new model of category judgment. The model hypothesizes
      that, when more attention is focused on a category, the psychological range of
      the category gets narrower (category-focusing hypothesis). We explain this
      hypothesis by using the metaphor of a "mental-box" model: the more attention that
      is focused on a mental box (i.e., a category set), the smaller the size of the
      box becomes (i.e., a cardinal number of the category set). The hypothesis was
      tested in an experiment (N = 40), where the focus of attention on prescribed
      verbal categories was manipulated. The obtained data gave support to the
      hypothesis: category-focusing effects were found in three experimental tasks
      (regarding the category of "food", "height", and "income"). The validity of the
      hypothesis was discussed based on the results.

PMID- 21735724
TI  - [Effects of feature similarity and discrimination category in a flanker task].
AB  - Three experiments were conducted to investigate the effects of feature similarity
      and discrimination category in a flanker task. Gabor patches were used as target
      and distractor stimuli for each experiment. In the first experiment, the target
      turned to minus or plus 45 deg from the vertical, whereas the orientation of the
      distractors changed between minus and plus 45 deg by 15 deg. For the second
      experiment, three conditions of the target orientation were used: minus or plus
      45 deg, minus 22.5 deg or plus 67.5 deg, and 0 deg or plus 90 deg. The
      orientation of the distractors changed between the orientations of the two
      targets by 22.5 deg. In the third experiment, the target turned to minus or plus
      10 deg from the vertical, whereas the orientation of the distractors changed
      between minus and plus 40 deg by 5 deg. The results showed that responses to the
      target were affected by the difference between the orientations of the target and
      the distractors as well as the category of their orientations.

PMID- 21735725
TI  - [Japanese learners' processing time for reading English relative clauses analyzed
      in relation to their English listening proficiency].
AB  - The present study examined Japanese university students' processing time for
      English subject and object relative clauses in relation to their English
      listening proficiency. In Analysis 1, the relation between English listening
      proficiency and reading span test scores was analyzed. The results showed that
      the high and low listening comprehension groups' reading span test scores do not
      differ. Analysis 2 investigated English listening proficiency and processing time
      for sentences with subject and object relative clauses. The results showed that
      reading the relative clause ending and the main verb section of a sentence with
      an object relative clause (such as "attacked" and "admitted" in the sentence "The
      reporter that the senator attacked admitted the error") takes less time for
      learners with high English listening scores than for learners with low English
      listening scores. In Analysis 3, English listening proficiency and comprehension
      accuracy for sentences with subject and object relative clauses were examined.
      The results showed no significant difference in comprehension accuracy between
      the high and low listening-comprehension groups. These results indicate that
      processing time for English relative clauses is related to the cognitive
      processes involved in listening comprehension, which requires immediate
      processing of syntactically complex audio information.

PMID- 21735726
TI  - [The relationship between grandparent role and subjective well-being of young
      olds].
AB  - This study explores the influence of self-processes involving grandparenthood on
      the frequency of contact with grandchildren and grandparent satisfaction, and the
      influence of these self-processes, frequency of contact, and grandparent
      satisfaction on subjective well-being. A mail survey was conducted with randomly
      selected people between 65-74 years of age (N = 226) living in a city. The
      results showed that grandparent centrality and grandparent identity meanings
      influenced the frequency of contact with grandchildren. Grandparent-identity
      meanings influenced grandparent satisfaction. Additionally, grandparent-identity
      meanings and grandparent satisfaction influenced subjective well-being. The
      findings suggest that only grandparent-identity meanings in self-processes of
      grandparenthood influenced grandparent satisfaction and subjective well-being.

PMID- 21735727
TI  - [Construction of the Literary Response Questionnaire for Japanese (LRQ-J)].
AB  - Readers may have various experiences while reading a narrative, such as imagining
      the world described in the narrative, empathizing with the protagonist, and
      thinking about the author of the narrative or the real world. Referred to as
      "reader response" in literary theory, these experiences are important topics in
      the study of a reader's interactions with a literary text. To investigate
      differences among individuals in the degree of openness to these experiences
      during narrative comprehension, we translated the Literary Response Questionnaire
      (LRQ) developed by Miall and Kuiken (1995) and selected 37 items from the
      original scale to develop a Japanese version (LRQ-J). This survey was
      administered to 497 undergraduate students. The results showed that all subscales
      of the LRQ-J had internal consistency. Respondents' scores showed significant
      correlations with fantasy proneness, imaginative involvement, imagery vividness,
      and ego-resiliency. The results suggest that the LRQ-J has sufficient reliability
      and validity. The psychological characteristics of experiences assessed by the
      LRQ-J are discussed.

PMID- 21735728
TI  - [Effects of relational efficacy on two attachment functions: evidence from
      romantic relationships and same-sex friendships].
AB  - This study investigated how relational efficacy affects functions of safe haven
      and secure base in romantic relationships and same-sex friendships. Relational
      efficacy, which is a shared or intersubjective efficacy of relationship partners,
      refers to a pair's belief that they can mutually coordinate and integrate their
      resources to prevent and resolve any problems. Participants were 97 dating
      heterosexual couples and 119 same-sex friendships. Multilevel structural equation
      modeling suggested that relational efficacy promotes the safe haven function and
      the secure base function in romantic relationships and same-sex friendships,
      controlled for sex, relationship longevity, irreplaceability, attachment anxiety,
      and attachment avoidance. Additionally, the effects of relational efficacy on the
      safe haven function and the secure base function in romantic relationships are
      stronger than in same-sex friendships. These results are discussed in terms of
      the association between intersubjective processes in close relationships and
      individuals' hedonic/eudaimonic well-being.

PMID- 21735729
TI  - [Effects of instructions on Baumtest drawings by elderly people].
AB  - Previous studies using the Baumtest (Tree-Drawing Test) reported that tree
      drawings by elderly people rarely show trees with crowns, in comparison to trees
      drawn by younger people. This difference may be an index of developmental changes
      resulting from aging. However, since these studies instructed participants to
      draw a single fruit-bearing tree, the kinds of trees that elderly people
      visualized may have been different from those visualized by younger people. In
      this study, 111 mentally healthy people over 65 years of age were divided into
      two groups: Group 1 (N = 61, mean age = 72.7 years) was asked to draw a single
      tree and Group 2 (N = 50, mean age = 73.4 years) was asked to draw a single fruit
      bearing tree. The results show that the frequency of trees with crowns drawn by
      Group 1 was lower than Group 2 (Chi2(1) = 21.04, p < .01). This suggests that the
      decrease in trees with crowns drawn by elderly people resulted from differences
      in instructions, in addition to possible developmental changes.

PMID- 21735730
TI  - [Juvenile delinquents' loneliness as represented on the Doll Location Test].
AB  - This study examined the validity of the indices of Hatta's Doll Location Test
      (DLT) to represent the interpersonal structure of juvenile delinquents. Japanese
      juvenile delinquents (N = 215) in detention were asked to fill out the
      Differential Loneliness Scale and to represent their typical interpersonal
      relations using the DLT. The results showed that the presence, the order, the
      distance, and the height of the figures were related to loneliness. However, the
      direction of placing the figures did not show the expected relationship with
      loneliness. Furthermore, the relationships between the indices and loneliness
      were different according to the type of person represented. The results suggest
      that distance was valid as an index of cohesion, although height could
      discriminate the intimate group from the others.

PMID- 21735731
TI  - [What is cerebral small vessel disease?].
AB  - An accumulating amount of evidence suggests that the white matter
      hyperintensities on T2 weighted brain magnetic resonance imaging predict an
      increased risk of dementia and gait disturbance. This state has been proposed as
      cerebral small vessel disease, including leukoaraiosis, Binswanger's disease,
      lacunar stroke and cerebral microbleeds. However, the concept of cerebral small
      vessel disease is still obscure. To understand the cerebral small vessel disease,
      the precise structure and function of cerebral small vessels must be clarified.
      Cerebral small vessels include several different arteries which have different
      anatomical structures and functions. Important functions of the cerebral small
      vessels are blood-brain barrier and perivasucular drainage of interstitial fluid
      from the brain parenchyma. Cerebral capillaries and glial endfeet, take an
      important role for these functions. However, the previous pathological
      investigations on cerebral small vessels have focused on larger arteries than
      capillaries. Therefore little is known about the pathology of capillaries in
      small vessel disease. The recent discoveries of genes which cause the cerebral
      small vessel disease indicate that the cerebral small vessel diseases are caused
      by a distinct molecular mechanism. One of the pathological findings in hereditary
      cerebral small vessel disease is the loss of smooth muscle cells, which is an
      also well-recognized finding in sporadic cerebral small vessel disease. Since
      pericytes have similar character with the smooth muscle cells, the pericytes
      should be investigated in these disorders. In addition, the loss of smooth muscle
      cells may result in dysfunction of drainage of interstitial fluid from
      capillaries. The precise correlation between the loss of smooth muscle cells and
      white matter disease is still unknown. However, the function that is specific to
      cerebral small vessel may be associated with the pathogenesis of cerebral small
      vessel disease.

PMID- 21735732
TI  - [Classification of etiologic subtypes for transient ischemic attacks: clinical
      significance of lacunar transient ischemic attack].
AB  - BACKGROUND: Lacunar transient ischemic attack (lacunar TIA) may have been
      underestimated because of diagnostic difficulties. The aim of our study was to
      classify TIAs by etiologic subtypes, especially using defined criteria for
      diagnosis of lacunar TIA and clarify clinical characteristics of lacunar TIA.
      METHOD: 105 TIA patients out of consecutive 1,244 patients with acute ischemic
      stroke admitted to our hospital between January 2007 and June 2010 were enrolled
      in the present study. TIA was defined as an acute focal neurological deficit
      lasting less than 24 hours, suspected to be of cerebrovascular origin regardless
      of ischemic lesions on MRI. TIAs were classified to 5 etiologic subtypes; (1)
      cardioembolic TIA, (2) atherothrombotic TIA, (3) lacunar TIA, (4) other
      etiologies, and (5) undetermined etiology and clinical characteristics in each
      subtype and the incidence of recurrent stroke after TIA were investigated.
      Lacunar TIA was diagnosed if the following criteria were fulfilled; (1) presence
      of lacunar infarct on MRI and/or the presence of unilateral dysfunction of at
      least two of three body parts (face, arm, leg) in the absence of cortical
      dysfunction presumed due to subcortical ischemia. (2) absence of cardiac sources
      of embolism and large artery atherosclerosis. RESULTS: In 105 patients with TIA,
      lacunar TIA was the most frequent etiology (31%) followed by cardioembolic TIA
      (27%), atherothrombotic TIA (19%), undetermined etiology (18%), and other
      etiologies (6%). In patients with lacunar TIA, history of repeated TIA was more
      frequent and systolic blood pressure on admission was higher significantly than
      in cardioembolic TIA. Six of 105 patients had experienced recurrent stroke after
      TIA during admission. Among these 6 patients, 3 patients were diagnosed as
      lacunar infarctions. CONCLUSIONS: Lacunar TIA was most common TIA subtype in the
      present study. It is critical to identify lacunar TIA on admission because some
      patients with lacunar TIAs experience early recurrent stroke.

PMID- 21735733
TI  - [Peripheral neuropathy, myelopathy, cerebellar ataxia, and subclinical optic
      neuropathy associated with copper deficiency occurring 23 years after total
      gastrectomy].
AB  - We report a 61-year-old man with slowly progressive gait disturbance and
      paresthesia in the lower extremities following a total gastrectomy for gastric
      cancer 23 years previously. The patient presented with hyperreflexia, peripheral
      sensory neuropathy, and cerebellar ataxia. Magnetic resonance imaging showed
      atrophy of the cerebellum, and electrophysiological findings suggested the
      presence of disorder in both sides of the pyramidal tract, dorsal column,
      peripheral nerves, and optic nerve. Laboratory findings revealed anemia,
      neutropenia, and a remarkably low serum copper level (10 microg/dl; normal: 68
      128). His serum vitamin E was slightly low and his serum vitamin B12 was within
      the normal limits. After administering an oral copper supplement, his symptoms
      improved with normalization of the serum copper level. We need to pay attention
      to myeloneuropathy caused by copper deficiency if the patient has a past history
      of total gastrectomy.

PMID- 21735734
TI  - [A case of POEMS syndrome with enlarged pancreas due to IgG4-related autoimmune
      pancreatitis].
AB  - A 57-year-old man developed bilateral hands and feet numbness, followed by
      weakness with the legs and skin pigmentation. These symptoms became gradually
      worsened, and we made a diagnosis of POEMS syndrome because of progressive
      polyneuropathy, skin changes, IgG lambda type monoclonal proteinemia, and
      elevated level of serum vascular endothelial growth factor (VEGF). Diffusely
      enlarged pancreas was noticed in computed tomography. Serological, radiological,
      and histological findings revealed enlarged pancreas was due to IgG4-related
      autoimmune pathogenesis. After high dose chemotherapy with autologous peripheral
      stem cell transplantation, his clinical manifestations, IgG lambda type
      monoclonal proteinemia, and elevated level of serum VEGF were improved, whereas
      diffuse enlargement of the pancreas did not change. This is the first case report
      of POEMS syndrome accompanied with IgG4-related autoimmune pancreatitis. Co
      existence of monoclonal and polyclonal plasma proliferative changes in the
      present patient may provide keys to clarify common mechanisms shared by these two
      rare disorders, POEMS syndrome and IgG4-related autoimmune disease.

PMID- 21735735
TI  - [An adult case of pandemic (H1N1) 2009 influenza associated encephalopathy].
AB  - A healthy 40-year-old man was admitted to our hospital because of impaired
      consciousness and convulsions starting five days after a high fever. Though rapid
      influenza diagnostic tests were negative, RT-PCR assay detected influenza A
      (H1N1) 2009 viral RNA from nasopharyngeal swab specimens. Initially high
      concentrations of interleukin-6 (IL-6) in serum and cerebrospinal fluid decreased
      as the symptoms improved, as with past influenza-associated encephalopathy cases.
      Scattered high signal intensity lesions in the cerebral cortex and right medial
      thalamus on magnetic resonance imaging (MRI) disappeared, and diffuse brain
      atrophy remained. It is necessary to be aware of the possibility of healthy
      adults developing pandemic 2009 influenza A (H1N1)-associated encephalopathy and
      that rapid influenza diagnostic tests have limited accuracy.

PMID- 21735736
TI  - [An autopsied case of senile onset frontotemporal lobar degeneration].
AB  - A Japanese male with no family history of neurological disease or dementia showed
      behavioral abnormalities including egocentric and antisocial behavior at the age
      of 80. Over the next few years, other psychiatric symptoms such as allotriophagy
      and stereotypical behavior were also observed and his abnormal behavior became a
      social problem. Neurological examination revealed no apparent motor
      abnormalities, pyramidal and extrapyramidal signs, or ataxia. Aphasia, including
      semantic dementia was not apparent. The severity of memory disturbance was
      relatively milder than his psychiatric symptoms. Daily living activities and
      conversational ability were relatively maintained until shortly before his death
      at the age of 86. The clinical diagnosis was Alzheimer disease. Autopsy revealed
      that the brain weighed 950 g; frontotemporal atrophy with lateral ventricular
      dilatation was apparent. Neuron loss, gliosis, and tissue rarefaction were
      recognized in the frontotemporal cortex, subiculum, transentorhinal cortex,
      amygdala, and insular cortex and were particularly noticeable in the superficial
      layer of the cortex. Many ubiquitin-positive/TDP-43 positive but tau-negative
      dystrophic neurites with a few neuronal cytoplasmic inclusions were widely
      observed. Neuronal cytoplasmic inclusions were also observed in the dentate gyrus
      of the hippocampus. Although the spinal cord was not investigated, there was no
      apparent involvement of the motor neuron system. Small numbers of neurofibrillary
      tangles and senile plaques were observed, corresponding to Braak stage II and
      CERAD stage B, respectively. Argyrophilic grains, Lewy bodies and Pick bodies
      were not observed. The patient was pathologically diagnosed with frontotemporal
      lobar degeneration with ubiquitin-positive/TDP-43-positive inclusions (FTLD-TDP)
      and without motor neuron disease. No mutation was found in the TDP-43 gene. We
      considered the psychiatric symptoms and head CT findings of the present patient
      to be important observations for helping to discriminate between Alzheimer
      disease or other neurodegenerative diseases with dementia, and FTLD-TDP.

PMID- 21735737
TI  - [Evaluation of blood flow and the cross-sectional area of internal jugular vein
      in Japanese multiple sclerosis and neuromyelitis optica patients].
AB  - Zamboni et al proposed a new hypothesis for the pathomechanisms of multiple
      sclerosis (MS): chronic cerebrospinal venous insufficiency (CCSVI). Using Doppler
      ultrasound and venograms, they found severe extracranial venous stenosis in MS
      patients. They suggested that a venous obstruction in the neck caused a reflux
      back into the brain, which led to edema and demyelination. We examined the blood
      flow and the cross-sectional area of the internal jugular veins using Doppler
      ultrasound (Vivid 7 PRO, GE Health Japan, Tokyo) in 17 MS (8 males and 9 females;
      20-58 years of age, median 38 years) and 11 neuromyelitis optica (NMO) Japanese
      patients (1 male and 10 females; 23-60 years of age, median 44 years). Nine of
      the 11 NMO patients were seropositive for anti-aquaporin4 antibodies. We did not
      find any obstruction or stenosis of the internal jugular veins in any patient.
      Other disorders such as bilateral internal and external jugular venous ligation
      or radical neck dissection, which result in venous stasis, are not known causes
      of demyelination in the central nervous system. Our data also does not support
      the hypothesis of CCSVI theory, despite the fact that our study was limited to a
      small group of patients and the examination was performed only using Doppler
      ultrasound.

PMID- 21735738
TI  - [Longitudinally extensive spinal cord lesion associated with intramedullary
      metastasis on MRI may represent pencil-shaped softening of the spinal cord].

PMID- 21735739
TI  - [Recurrent cerebral infarction and antithrombotic medication].

PMID- 21735740
TI  - [Effects of anticoagulant therapy for rapidly progressive interstitial
      pneumonias].
AB  - To clarify the effects of anticoagulant therapy, we investigated patients with
      rapidly progressive interstitial pneumonias, retrospectively. We defined rapidly
      progressive pneumonia as idiopathic or secondary interstitial pneumonia with
      acute exacerbation of respiratory symptoms within 2 months, without infection or
      heart failure. A total of 20 cases admitted to our hospital between April 1999
      and January 2010 met our criteria. Of those 20 cases, 6 were non-idiopathic
      pulmonary fibrosis (non-IPF), 3 were IPF, 6 were amyopathic dermatomyositis
      (ADM), 2 were DM, 2 were rheumatoid arthritis, and 1 was mixed connective-tissue
      disease. We divided the 20 cases into two groups according to whether they were
      treated with anticoagulant therapy (dalteparin and/or warfarin) (group A, n = 11)
      or not (group B, n = 9), and compared their outcomes. They were all given
      standard therapy. There was significantly better survival time in group A than in
      group B by the Kaplan-Meier survival curve (p = 0.0389). Anticoagulant therapy
      may improve the survival of patients with rapidly progressive interstitial
      pneumonias.

PMID- 21735741
TI  - [Educational usefulness of lung auscultation training with an auscultation
      simulator].
AB  - OBJECTIVE: We examined the educational usefulness of lung auscultation training
      with an auscultation simulator "Mr. Lung". METHODS: Auscultation training was
      conducted for fifth-year students of the Medical Department of the University of
      Miyazaki, and consisted of a lecture by a pulmonologist (Board Certified Member
      of the Japanese Respiratory Society) and skill training using Mr. Lung for a
      total of 90 min. We compared the percentages of students who correctly identified
      4 adventitious sounds before and after training. We also investigated the
      responses to a self-report questionnaire on self-evaluation after training,
      auscultation experiences before training, and opinions regarding medical
      education with the simulator. RESULTS: The subjects' correct answer rate before
      training was 40% or less and that for the correct identification of rhonchi was
      the lowest (5%). The correct answer rate, which was not influenced by previous
      experience of auscultation, significantly increased after training (80% or more).
      In the self-report questionnaire, about 90% of the students answered that the
      ability to identify lung sounds by auscultation was necessary for all doctors and
      that the simulator was effective for acquiring this skill. CONCLUSION: The
      auscultation simulator may be useful for medical students not only to enhance
      auscultatory skills but also to realize the importance of auscultation in
      clinical examination.

PMID- 21735742
TI  - [Siblings with familial interstitial pneumonia].
AB  - The index case was a 71-year-old man with no smoking history. He was given a
      diagnosis of idiopathic interstitial pneumonia at the age of 65. He was admitted
      to our hospital because of persistent cough and dyspnea on exertion. Two months
      after initiation of corticosteroid treatment he died of acute exacerbations of
      interstitial pneumonia. Among his family, four of seven brothers had interstitial
      pneumonia and all three sons of his were also found to have interstitial
      pneumonia, and of these seven patients six had a history of smoking. The average
      age at diagnosis of his generation was 66.5 and that of his son's generation was
      45.3. In proband generation chest CT showed traction bronchiectasis or
      honeycombing in subpleural lesions. In addition, it revealed centrilobular
      micronodules and interlobular reticular shadow in the second generation. We found
      2 single nucleotide polymorphisms of surfactant protein C gene in all children of
      the proband.

PMID- 21735743
TI  - [Three cases of Mycobacterium kansasii pulmonary diseases in previously healthy
      young women].
AB  - Mycobacterium kansasii pulmonary diseases account for 20% of cases of non
      tuberculous mycobacteria. Most patients are male. However, a recent study has
      found that radiological examinations in female patients often reveal nodular,
      bronchiectatic opacities. We describe 3 young women with cavitary opacities.
      Patient 1 was a 35-year-old woman in whom thin-walled cavitary opacities were
      detected in the upper lobe during a routine checkup. Sputum examination and
      fiberoptic bronchoscopy led to a diagnosis of M. kansasii pulmonary disease.
      Patient 2 was a 23-year-old woman who presented with hemoptysis. Thin-walled
      cavitary opacities were detected in the right upper lobe. Infection with M.
      kansasii was diagnosed after a sputum examination. Patient 3 was a 43-year-old
      woman in whom thin-walled cavitary opacities were detected in the left upper lobe
      during a routine checkup. Infection with M. kansasii was diagnosed after a
      fiberoptic bronchoscopic examination. Patient 1 was successfully treated with
      rifampicin, ethambutol, and levofloxacin, and patients 2 and 3 were successfully
      treated with isoniazid, rifampicin, and ethambutol. The possibility of M.
      kansasii pulmonary diseases should be considered in a previously healthy young
      woman with thin-walled cavitary opacities in the upper lobe.

PMID- 21735744
TI  - [A case of bronchocentric granulomatosis associated with Aspergillus clusters
      that was difficult to distinguish from lung cancer].
AB  - A 69-year-old man was examined for investigation of a nodular shadow with
      calcification detected on computed tomography of the chest. He showed no features
      of allergic bronchopulmonary aspergillosis (ABPA), such as bronchial asthma or
      eosinophilia. We could not distinguish his disease status from lung cancer and
      performed upper lobectomy of his right lung. Pathological examination revealed
      bronchocentric granulomatosis (BCG) with Aspergillus clusters. Subsequent
      serological testing demonstrated high levels of IgE-RIST and IgE-RAST
      (Aspergillus) whereas anti-Aspergillus precipitating antibody was not detectable.
      We believe that Aspergillus clusters may have been present in this patient for
      several years, and the pathological findings might be manifested as an
      asymptomatic localized allergic inflammation. BCG is a pathological component of
      ABPA. This case, of a localized allergic reaction, is considered very valuable
      for understanding the underlying mechanism of the onset of ABPA.

PMID- 21735745
TI  - [A case of multicentric Castleman disease with massive infiltration of
      plasmacytes presenting IgG4].
AB  - A 42-year-old Japanese woman was referred to our university hospital due to
      progressive anemia and bilateral hilar lymphadenopathy with diffuse ground-glass
      attenuation on chest computed tomography in December 2009. She had suffered from
      exertional dyspnea and fatigue for several months. Laboratory findings on
      admission demonstrated leukocytosis (10,950/ul), elevation of C-reactive protein
      (4.7 mg/dl), IL-6 (19.9 pg/ml), IgG4 (567 mg/dl) and polyclonal hyper gamma
      globulinemia. Chest computed tomography represented mediastinal and bilateral
      hilar lymphadenopathy with diffuse centrilobular fine nodules and intralobular
      septal thickening. Histopathological findings of the specimens obtained by
      thoracoscopic lung and mediastinal lymph node biopsies revealed massive
      infiltration of IgG4-positive plasma cells in lung tissue and lymph nodes.
      Pathological findings and high levels of C-reactive protein and interleukin-6
      suggested a diagnosis of multicentric Castleman's disease (MCD). In addition,
      pathological findings of peribronchiolar infiltration of IgG4-positive plasma
      cells and lymphoid follicles with infiltration of IgG4-positive plasma cells with
      a high level of IgG4 were indicative of the complication of IgG4-related lung
      disease. Radiological and serological findings improved rapidly soon after the
      initiation of oral corticosteroid treatment. It was speculated that this case
      indicated the close relationship between MCD and IgG4-related lung disease.

PMID- 21735746
TI  - [A case of melioidosis occurring after a long-term stay in Vietnam that developed
      pulmonary cavitation and relapsed with multiple pulmonary nodules].
AB  - A 69-year-old man complained of fever in September 2009, after returning from
      Vietnam where he has been working for 20 years. He had diabetes mellitus and was
      on diabetic oral medication. He was examined at a nearby hospital, and found out
      to have pneumonia with cavity formation in the right upper lobe which was found
      out to be not due to tuberculosis. Although the patient once recovered with
      antibacterial medicine, after a few months, in January 2010, he was admitted to
      our hospital because of recurrent fever. Computed tomography revealed multiple
      pulmonary nodules which were thought to be pulmonary emboli, as well as
      subcutaneous abscess, spleen abscess, and kidney abscess. Blood test showed that
      he also had DIC. As Burkholderia pseudomallei was cultured from the subcutaneous
      abscess and blood, was diagnosed as melioidosis. The patient was treated with
      meropenem for 8 weeks, and then a maintenance oral antibacterial medicine was
      continued for the next 6 months. The patient fully recovered after those
      treatments and has not relapsed since then. This is the ninth case report of
      melioidosis in Japan which is an imported infectious disease.

PMID- 21735747
TI  - [A case of Lemierre syndrome].
AB  - Classic Lemierre syndrome is a septic internal jugular venous thrombophlebitis
      secondary to oropharyngeal anaerobic infection in adolescents and young adults.
      Upper respiratory tract infection is the most common antecedent. We report a case
      of Lemierre syndrome as a rare infectious disease. A 20-year-old man complained
      of high fever, right neck discomfort and chest pain. Chest X-ray revealed
      infiltrative shadows, suggesting bacterial pneumonia. Although cefcapene pivoxil
      hydrochloride hydrate (CFPN-PI) was given in a local clinic, his symptoms did not
      improve. Then he was referred to our hospital. Chest CT findings showed bilateral
      multiple nodular shadows with small cavities, suggesting septic embolization.
      Fusobacterium necrophorum was cultured from specimen of the blood, and an
      enhanced neck CT scan showed thrombosis in the right internal jugular vein. These
      findings led us to a diagnosis of Lemierre syndrome. Four weeks of antibiotics
      and anticoagulants ameliorated inflammatory findings in blood, but internal
      jugular vein thrombosis remained. Currently, there is no consensus opinion on the
      use of anticoagulation in patients with Lemierre syndrome complicated by septic
      internal jugular thrombosis and embolism. Early and effective antibiotics therapy
      may prevent the development of the syndrome and its associated complication,
      although it is unclear whether the outcome will be favorable.

PMID- 21735748
TI  - [Legionella pneumonia in a patient with positive culture results of Legionella
      pneumophila serotype 1 from bronchoalveolar lavage fluid but negative urinary
      antigen test results].
AB  - A 39-year-old man presented to a local physician complaining of fever, headache
      without cough or sputum. Abnormal shadows were found on chest X-ray films.
      Pneumonia was diagnosed and he was referred to our hospital, where chest computed
      tomography showed bilateral, multifocal, and patchy ground-glass opacities.
      Neither the urinary antigen test for Streptococcus pneumoniae nor that for
      Legionella was positive. Because he had visited a public spa several days before
      developing the fever and headache, and because hypophosphatemia was identified,
      we then suspected Legionella pneumonia. Bronchoalveolar lavage fluid yielded
      positive culture of Legionella pneumophila serotype 1. The Legionella urinary
      antigen is known to detect Legionella pneumophila serotype 1 infection; however,
      sensitivity and specificity of the test are 60-95% and > 99%, but care should be
      taken when urinary antigen test results are negative in suspected cases of
      Legionella pneumophila serotype 1 pneumonia. In the present case, bronchoalveolar
      lavage fluid was a useful method for diagnosing Legionella pneumonia.

PMID- 21735749
TI  - [Occurrence of organizing pneumonia after radiation therapy for postoperative
      breast cancer].
AB  - Three cases of organizing pneumonia (OP) that occurred after planned radiation
      therapy for postoperative breast cancer are reported. All patients received
      tangential radiation therapy and adjuvant tamoxifen (TAM) for postoperative
      breast cancer. Two patients developed fever and cough; one was asymptomatic.
      Chest radiography and computed tomography demonstrated peripheral alveolar
      opacities outside the radiation field. Bronchoalveolar lavage showed an elevated
      total cell count with a high percentage of lymphocytes, as well as elevated
      eosinophil levels in two cases. Transbronchial lung biopsy revealed a histologic
      pattern consistent with organizing pneumonia. For the two symptomatic cases,
      treatment with corticosteroids reduced clinical symptoms promptly and improved
      imaging findings. The single asymptomatic case improved without treatment. The
      number of such reported cases has increased in recent years, but the etiology is
      unclear. In the three cases presented, TAM combined with radiation therapy may
      have been the cause of the OP.

PMID- 21735750
TI  - [A case of imatinib mesylate-induced pneumonitis based on the detection of
      epithelioid granulomas by video-assisted thoracoscopic surgery biopsy in a
      patient with chronic myeloid leukemia].
AB  - A 79-year-old man with chronic myeloid leukemia was referred to our department
      because of dry cough and low-grade fever, 272 days after commencing imatinib
      mesylate (Gleevec). High resolution computed tomography (HRCT) showed tiny
      scattered centrilobular nodules and ground-glass opacities throughout both lung
      fields, suggesting drug-induced pneumonitis. A thoracic video-assisted
      thoracoscopic surgery (VATS) biopsy specimen from the centrilobular nodules in
      the right upper lobe demonstrated patchy distribution of epithelioid cell
      granulomas and intra-alveolar organization. Most of those lesions were
      predominantly located in the alveolar spaces, which implicated non-transbronchial
      distribution. Following drug cessation alone, the patient's general condition and
      radiological abnormalities improved.

PMID- 21735751
TI  - [A case of pulmonary malignant melanoma mimicking lung abscess].
AB  - An 84-year-old man was admitted with paresis of the right lower limb. Hemorrhagic
      lesions were demonstrated in the left frontoparietal lobe and cerebellum by
      cranial computed tomography (CT) and magnetic resonance imaging (MRI). Chest CT
      revealed an ill-defined mass measuring 4 x 6 cm in the left lower lobe of the
      lung, although bronchoscopic examination failed to obtain pathological diagnosis.
      Clinical diagnosis of primary lung cancer with multiple brain metastases was
      made, and he underwent whole brain radiotherapy. The pulmonary and cerebral
      lesions mimicked abscesses during his clinical course, and he died of respiratory
      failure due to bilateral pneumonia three months after admission. Autopsy revealed
      that both the pulmonary and brain lesions were malignant melanomas, but no other
      melanoma lesions could be identified despite meticulous investigation. Although
      malignant melanoma with an unknown primary site is rare in Japan, careful
      evaluation of the CT and MRI findings might be the key to correct diagnosis in
      this case.

PMID- 21735752
TI  - [Therapeutic approach for severe allergic conjunctival diseases--emergence of
      immunosuppressant eye drops].

PMID- 21735753
TI  - [Double-masked, phase III comparative study of the combination ophthalmic
      solution of the 1% dorzolamide hydrochloride/0.5% timolol maleate (MK-0507A) in
      patients with glaucoma and ocular hypertension].
AB  - OBJECTIVE: To investigate the IOP-lowering effect and safety of a combined
      ophthalmic solution (MK-0507A) of 1% dorzolamide hydrochloride and 0.5% timolol
      maleate in comparison to 0.5% timolol maleate (timolol), and 1% dorzolamide
      hydrochloride and 0.5% timolol maleate concomitant therapy (concomitant therapy).
      SUBJECTS AND METHODS: This study was conducted in patients with either primary
      open angle glaucoma or ocular hypertension. The patients with IOP > or = 18 mmHg
      following the administration of timolol for 4 weeks during the observation period
      (474 patients) were randomized to receive either MK-0507A (189 patients), timolol
      (92 patients) or concomitant therapy (193 patients) during the treatment period
      and when evaluated for IOP at Week 8. The primary evaluation criteria were change
      in 2 hour IOP from baseline to Week 8. RESULTS: The least square means of the
      changes in hour 2 IOP from baseline to Week 8 were -2.50 mmHg, -1.82 mmHg and 
      2.78 mmHg in the MK-0507 A group, timolol group and concomitant therapy group,
      respectively. MK-0507A demonstrated a significant reduction in IOP compared to
      timolol. Further- more, the 95% confidence interval of the difference between MK
      0507A and concomitant groups satisfied the pre-specified criteria for non
      inferiority confirming the non-inferiority of MK-0507A relative to the
      concomitant therapy. In addition, MK-0507A had safety comparable to that of
      timolol and concomitant therapy. CONCLUSION: MK-0507A has a significantly
      superior IOP-lowering effect relative to timolol. MK-0507A also showed a non
      inferior IOP-lowering effect relative to the concomitant therapy. MK-0507A was
      safe compared to both timolol and concomitant therapy.

PMID- 21735754
TI  - [A prospective, observational, all-prescribed-patients study of cyclosporine 0.1%
      ophthalmic solution in the treatment of vernal keratoconjunctivitis].
AB  - PURPOSE: To evaluate the effectiveness and safety of topical cyclosporine 0.1% in
      patients with vernal keratoconjunctivitis (VKC). METHODS: All patients who were
      prescribed topical cyclosporine 0.1% during the 2 year period after market launch
      were registered and followed up for 6 months. We assessed the severity of 6
      subjective ocular symptoms, such as itching and 10 objective signs, such as giant
      papillae in the tarsal conjunctiva. RESULTS: All scores for symptoms and signs in
      2597 patients with VKC significantly decreased throughout a 6-month follow-up.
      For total symptoms scores, mean changes from baseline at 1, 3, and 6 months were 
      4.0, -4.8, and -5.1, respectively. Total sign scores were -4.6, -6.1, and -6.5,
      respectively. Thirty percent of topical steroid users were able to discontinue
      the steroids within 3 months. Adverse drug reactions (ADRs) were found in 7.44%
      of patients, the most common ADR being eye irritation. Ocular infections were
      observed in 1.44% of patients. During long-term use of topical cyclosporine 0.1%,
      there was no increase in the incidence of ADR and no late-onset ADRs.
      CONCLUSIONS: Topical cyclosporine 0.1% is an effective and safe treatment for VKC
      over the long term, provided care is exercised to avoid the occurrence of
      infection.

PMID- 21735755
TI  - [Effects of vitrectomy as a treatment for proliferative diabetic retinopathy in
      young patients].
AB  - PURPOSE: To investigate the effects of vitrectomy as a treatment for the
      proliferative diabetic retinopathy (PDR) in patients under 40 years old. METHODS:
      Sixty eyes of 37 patients under 40 years old with PDR who had undergone
      vitrectomy for the first time in Juntendo University Urayasu Hospital were
      included in this study. Preoperative condition, operation methods, visual acuity
      after operation and complications both during or after operation, especially
      neovascular glaucoma (NVG), were reviewed retrospectively. RESULTS: Visual acuity
      improved in 43 eyes (72%) by more than 0.2 logMAR compared to that before the
      operation, remained stable in 4 eyes (6%) and deteriorated in 13 eyes (22%) by
      more than 0.2 logMAR compared to that before operation. Optic atrophy and
      phthisis caused by NVG constituted 69% of the causes of complicated final visual
      acuity. Male patients and patients who had both hypertension and proteinuria had
      significantly higher prevalence of NVG after vitrectomy (p < 0.05), and patients
      who retained their lens after the first vitrectomy had a significantly lower
      prevalence of NVG after the operation (p < 0.05). CONCLUSIONS: In young PDR
      patients under 40 years old, postoperative NVG was the main reason for severe
      visual impairment. Multifactorial causes, both general and ophthalmic seem to be
      implicated in the onset and progression of NVG derived from PDR.

PMID- 21735756
TI  - [Survey of triamcinolone-related non-infectious endophthalmitis].
AB  - PURPOSE: To survey non-infectious endophthalmitis related to triamcinolone
      acetonide (TA) for ocular diseases in Japan. SUBJECTS AND METHODS: A
      questionnaire was sent to the 24 committee members of the Japanese Retina and
      Vitreous Society requesting information regarding non-infectious endophthalmitis
      related to intravitreous TA administered from January through December 2009. The
      survey specifically covered the use of TA in intravitreal injections and
      intraoperatively during vitrectomy procedures. RESULTS: All 24 members responded
      to the survey involving intraviteal TA use in 562 eyes; 325 eyes for diabetic
      macular edema, 118 eyes for retinal vein occlusion, 91 eyes for uveitis, 11 eyes
      for age-related macular degeneration and 17 eyes had adjunctive use in retinal
      photocoagulation. Intraoperative use for visualizing vitreous was done in 6973
      eyes. Noninfectious endophthalmitis occurred in 9 eyes (1.6%) after intravitreous
      TA and 7 eyes (0.1%) after intraoperative TA. The most frequent symptom was
      blurred vision with no pain or mild conjunctival injection. Sudden severe
      anterior chamber and vitreous inflammation occurred beginning on the day
      following surgery, but it disappeared spontaneously without complications.
      CONCLUSIONS: It was found that non-infectious endophthalmitis occurred after
      intravitreous TA. Although the visual prognosis is good, this complication should
      be recognized by retina specialists.

PMID- 21735757
TI  - [Wide everting suture for involutional lower lid entropion].
AB  - PURPOSE: To describe a wide everting suture technique for involutional lower lid
      entropion and evaluate the outcomes of the procedure. METHODS: The procedure was
      performed as a modified Komoto procedure except that a wide suture was placed
      along the whole inversion lid length using a single nonabsorbable stitch. The
      criteria for recurrence were eyelashes contacting the cornea and keratopathy. The
      medical records of patients with a minimum follow-up of 3 months after the
      surgery were retrospectively examined. RESULTS: This study included 41 lower
      eyelids of 36 patients. The mean postoperative follow-up period was 10.8 months
      (range, 3-30 months). The recurrence rate was 7.3% (3/41). There were no
      postoperative complications such as ectropion. CONCLUSIONS: We found the wide
      everting suture was a simple, quick and minimally-invasive method of treating
      involutional entropion. Our results suggest that this procedure might correct
      both vertical and horizontal laxity and be effective for involutional entropion.

PMID- 21735758
TI  - [A case of left posterior inferior temporal infarction with right homonymous
      upper quadrantanopsia and alexia with agraphia for Kanji].
AB  - BACKGROUND: Alexia with agraphia usually represents damage in angular gyrus. We
      report an unusual case of alexia with agraphia caused by a posterior inferior
      temporal lesion. CASE REPORT: A 82-year-old, right-handed man was admitted
      because of reading disorder. Visual acuity was 0.7 OD and 0.7 OS. Goldmann
      perimetry revealed right homonymous upper quadrantanopsia. Standard Language Test
      of Aphasia revealed mild anomia and severe alexia with agraphia for kanji.
      Magnetic resonance imaging demonstrated left temporal and posterior infarction in
      the posterior cerebral artery region. Single photon emission computed tomography
      revealed decreased blood flow in the left inferior temporal, parahippocampal,
      fusiform, lingual and inferior occipital gyri. There were no significant lesions
      nor any decreased of blood flow in the angular gyrus. CONCLUSION: It is suggested
      that reading and writing of ideograms such as Kanji is related not only to the
      angular gyrus but also to the posterior inferior temporal lobe and medial
      posterior lobe of the visual cortex.

PMID- 21735759
TI  - [Case report of melanoma-associated retinopathy associated with positive auto
      antibodies against retinal bipolar cells].
AB  - BACKGROUND: We report a case of melanoma-associated retinopathy (MAR) associated
      with positive auto-antibodies against retinal bipolar cells, which has been
      rarely reported in Japan. CASE REPORT: A 33 year-old woman noticed shimmering
      vision, photopsias, blurred vision, and night blindness OS in April 2009, and
      visited Kagoshima Miyata Eye Clinic in May 2009. She had been continuously
      treated for malignant melanoma on her left finger since 2007. At her initial
      visit, the corrected visual acuity was 1.5 OD and 1.2 OS, and slit-lamp
      examination revealed clear ocular media OU. Funduscopic examination showed normal
      appearance of the retina OU, except for a mild narrowing of the retinal arteries
      OS. Humphrey field analyzer revealed a reduction of retinal sensitivity within
      the central 30 degrees OS. The maximum left eye response of electroretinogram
      (ERG) showed a negative waveform. The immuno-cytochemical test revealed
      antibodies against retinal bipolar cells, which confirmed the diagnosis of MAR.
      CONCLUSION: Characteristic subjective symptoms, Humphrey field analyzer and ERG
      are useful for the diagnosis of MAR.

PMID- 21735760
TI  - [Ethical issues of the research with psychiatric drugs].

PMID- 21735761
TI  - [Patients with mental disturbances, clinical research and the use of placebos: a
      complex subject; dubious answers].

PMID- 21735762
TI  - Kainate receptors. Novel signaling insights.

PMID- 21735764
TI  - Doctoral degrees open new career doors.

PMID- 21735763
TI  - Tobacco products, exemptions from substantial equivalence requirements. Final
      rule.
AB  - The Food and Drug Administration (FDA) is issuing this final rule to establish
      procedures for requesting an exemption from the substantial equivalence
      requirements of the Family Smoking Prevention and Tobacco Control Act (Tobacco
      Control Act). The final rule describes the process and statutory criteria for
      requesting an exemption and explains how FDA reviews requests for exemptions.
      This regulation satisfies the requirement in the Tobacco Control Act that FDA
      issue regulations implementing the exemption provision.

PMID- 21735765
TI  - DNP or PhD: which is right for you?

PMID- 21735766
TI  - How has earning your DNP changed your career?

PMID- 21735767
TI  - Lymphedema in head and neck cancer.

PMID- 21735768
TI  - The case of the tired teenager.

PMID- 21735769
TI  - Fertility possible for male childhood cancer survivors.

PMID- 21735770
TI  - ONS President shares the 2011 state of the society.

PMID- 21735771
TI  - [Treatment of bilateral avascular necrosis of femoral head by free vascularized
      fibula grafting with unilateral fibula as donor].
AB  - OBJECTIVE: To investigate the effectiveness of free vascularized fibula grafting
      with unilateral fibula as donor in treatment of bilateral avascular necrosis of
      femoral head (ANFH). METHODS: Between June 2007 and January 2008, 14 patients
      with bilateral ANFH were treated with free vascularized fibula grafting with
      unilateral fibula as donor. There were 12 males and 2 females with an average age
      of 36.6 years (range, 17-57 years). The necrosis was caused by use of steroids in
      3 cases, consumption of alcohol in 4 cases, and idiopathic condition in 7 cases.
      According to Steinberg system, 16 hips were classified as stage II, 10 hips as
      stage III, and 2 hips as stage IV. The preoperative Harris hip scores were 77.50
      +/- 4.19, 69.70 +/- 2.76, 59.50 +/- 0.50 in patients at stages II, III, and IV,
      respectively. The duration of operation and the bleeding volume were recorded.
      The X-ray examination, the Harris hip score, and the complications were used to
      evaluate the effectiveness. RESULTS: The duration of the fibula osteotomy was 10
      32 minutes (mean, 20 minutes). The duration of the total operation was 100-240
      minutes (mean, 140 minutes). The bleeding volume was 200-500 mL (mean, 280 mL).
      All patients achieved healing of incision by first intention. The patients were
      followed up 12-40 months (mean, 24 months). One case had numbness and hypesthesia
      of the anterolateral thigh; 1 case had abnormal sensation of the dorsal foot; 1
      case had discomfort of the ankle; and they restored to normal at 1 year after
      operation. According to X-ray films 1 year after operation, the improvement was
      achieved in 23 hips (82.1%) and no deterioration in 5 hips (17.9%). At 1 year
      after operation, the Harris hip scores were 93.90 +/- 4.84, 88.50 +/- 8.13, and
      78.00 +/- 0.00 in patients at stages II, III, and IV, respectively, showing
      significant differences when compared with preoperative ones (P < 0.05).
      CONCLUSION: Unilateral free vascularized fibula grafting has lots of virtues,
      such as short surgical time, less bleeding volume, little injury, and good
      results of function recovery. It could be an effective and safe method in
      treating bilateral ANFH.

PMID- 21735772
TI  - [Mid-term effectiveness of two-stage hip prosthesis revision in treatment of
      infection after hip arthroplasty].
AB  - OBJECTIVE: To evaluate the mid-term effectiveness of two-stage hip prosthesis
      revision in the treatment of infection after hip arthroplasty. METHODS: Between
      April 2002 and November 2006, 12 cases of infection after hip arthroplasty were
      treated. There were 5 males and 7 females, aged from 47 to 72 years (mean, 59.8
      years). The femoral head arthroplasty was performed in 2 cases and total hip
      arthroplasty in 10 cases. Infection occurred 1 to 67 months after arthroplasty.
      According to the Segawa classification criteria, infections included type 2 in 1
      case, type 3 in 2 cases, and type 4 in 9 cases. The preoperative Harris score was
      36.7 +/- 6.1. Nine cases had elevated C reactive protein and 10 cases had
      elevated erythrocyte sedimentation rate. The results of bacterial culture were
      positive in 8 cases and negative in 4 cases. After the removal of the infected
      prosthesis and thorough debridement, antibiotic-loaded cement spacers or infected
      therapeutic temporary prosthesis were used as placeholders, and then the anti
      infection treatments were given after operations; two-stage hip prosthesis
      revisions were performed 3 to 10 months after debridement. RESULTS: In 1 patient
      who failed to control infection after debridement, infection was controlled after
      the second debridement and the antibiotic-loaded cement spacer as placeholder.
      Other patients achieved healing of incision by first intention, and no
      complication such as deep venous thrombosis and nerve injury occurred. All
      patients were followed up 3 to 8 years after revision (mean, 5.4 years). During
      the follow-up, no infection recurrence and joint dislocation occurred. Dull pain
      was present in 2 cases during activity and mild claudication in 3 cases at last
      follow-up. The Harris score was 81.6 +/- 4.5, showing significant difference (t =
      52.696, P = 0.000) when compared with preoperative score. The X-ray films showed
      that no prosthesis loosening and obvious subsidence were observed, and bone graft
      healed. CONCLUSION: The two-stage hip prosthesis revision has good infection
      control rate and mid-term effectiveness in treatment of infection after hip
      arthroplasty.

PMID- 21735773
TI  - [Diagnosis and treatment of anterior cruciate ligament cysts].
AB  - OBJECTIVE: To explore the diagnosis and treatment of anterior cruciate ligament
      (ACL) cysts of the knees. METHODS: The clinical data were retrospectively
      analysed from 13 patients with ACL cysts between December 2000 and August 2007.
      The patients included 7 males and 6 females with an average age of 46.3 years
      (range, 32-55 years). The locations were the left knee in 6 cases and the right
      knee in 7 cases. Seven cases had an obvious history of trauma, 4 cases had a
      history of chronic injury, and 2 cases had no obvious incentive factor. The
      disease duration was from 6 to 29 months (mean, 20 months). Anterior drawer test
      was positive in 1 case, pivot shift test was positive in 1 case, and McMurray
      test was positive in 3 cases. Six cases were preoperatively diagnosed by MRI. The
      cysts located near the tibial insertion in 6 cases, between the ACL and the
      posterior cruciate ligament in 3 cases, and near the femoral attachment in 4
      cases. All cysts were arthroscopically resected and had the pathohistological
      examination. RESULTS: The pathohistological examination showed mucoid
      degeneration of collagen and connective tissues, and the diagnosis result was ACL
      cyst. All incisions healed by first intention, and no complication occurred.
      Thirteen patients were followed up 2 to 5 years (mean, 2 years and 6 months). The
      symptoms of arthralgia, swelling, and interlocking of the affected knees
      disappeared. At 24 months postoperatively, the anterior drawer test was positive
      in 1 case, the pivot shift test was positive in 1 case, and McMurray test was
      positive in 4 cases. There was no recurrence during the follow-up. There were
      significant differences in the range of motion and Lysholm score between pre- and
      post-operation (P < 0.01). CONCLUSION: ACL cysts may be indicated by simple knee
      pain, especially when accompanied by limitation of joint motion without imaging
      evidence of osteoarthritis. The MRI finding is very important in the diagnosis of
      ACL cysts, and arthroscopic resection and debridement is the first choice in the
      treatment of ACL cysts.

PMID- 21735774
TI  - [Diagnosis and treatment of eosinophilic granuloma of long bones in children].
AB  - OBJECTIVE: To investigate the operative procedure and the effectiveness of
      eosinophilic granuloma (EG) of long bones in children. METHODS: Between January
      2005 and December 2009, 14 patients with EG of long bones were treated. There
      were 9 boys and 5 girls, aged from 1 to 13 years (mean, 6.5 years). The locations
      were femur in 5 cases, humerus in 4 cases, tibia in 2 cases, fibula in 1 case,
      and femur complicated with tibia in 2 cases. The disease duration was 7 days to
      10 months (median, 2 months). X-ray films showed that osteolytic destruction had
      clear boundary, which did not involve the epiphyseal plate. Of 14 cases, 12 cases
      of tumor were treated by curettage, autologous iliac bone or combined artificial
      bone graft repair, and 2 cases were treated by resection, autologous iliac
      reconstruction, plate and screw fixation. Five cases complicated with
      pathological fracture underwent reduction and fixation. RESULTS: All cases were
      diagnosed pathologically as having EG. All incisions healed by first intention. A
      total of 12 patients were followed up 1 to 4 years (mean, 2 years). The X-ray
      films showed tumor focus and pathological fracture healed within 3 to 4 months
      (mean, 3.5 months). Tibial lesion was found in 1 case of femoral tumor after 8
      months, and was cured after reoperation. No recurrence occurred in other 11
      cases. According to comprehensive assessing standard of X-ray film and joint
      function, the results of all cases were excellent. CONCLUSION: EG of long bones
      in children is more common in the femur and humerus. Tumor curettage and
      autologous iliac bone graft repair is an effective method, and postoperative
      prognosis is good. There may be multiple lesions, so long-term follow-up is
      needed.

PMID- 21735775
TI  - [Inhibition of aseptic loosening by receptor activator of nuclear factor kappa B
      ligand antibody in osteolysis model of mouse].
AB  - OBJECTIVE: Aseptic loosening of prosthesis is associated with periprosthetical
      osteolysis caused by osteoclast activation. Receptor activator of nuclear factor
      kappa B (NF-kappaB) ligand (RANKL)/receptor activator of NF-kappaB (RANK) signal
      pathway is fundamental in osteoclast activation. To determine whether RANKL
      antibody can inhibit inflammatory osteolysis in a osteolysis model of mouse.
      METHODS: Sixty female BALB/c mice (aged 8-10 weeks, weighing 18-20 g) were
      selected. The skull bone piece was harvested from 20 mice as the donor of bone
      graft; the subcutaneous air pouches (2 cm x 2 cm) models were established on the
      back of the other 40 mice and the skull bone piece was inserted into the air
      pouches. The 40 mice were equally divided into groups A (negative control group),
      B (positive control group), C (low-dose RANKL antibody group), and D (high-dose
      RANKL antibody group). At 1 day after bone graft, 0.5 mL PBS was injected into
      the pouch of group A, 0.5 mL PBS containing titanium particle into groups B, C,
      and D. At 2 days before the titanium particle was injected, RANKL antibody (0.1
      mL) were injected into the pouch of group C (50 microg/mL) and group D (500
      microg/mL), respectively every day for 2 days, and 0.1 mL PBS into groups A and
      B. At 14 days after bone implantation, the pouch membranes containing implanted
      bone were harvested for gross observation and histological analyse. RESULTS: All
      mice survived to the end of experiment, and incisions healed well. The gross
      observation showed that inflammatory responses, exudation, and vascular
      proliferation were obvious in group B, and were inconspicuous in groups A, C, and
      D. The histological analysis showed that significantly more infiltration of
      inflammatory cells, more obvious bone resorption, more bone collagen loss, and
      more positive staining area were observed in group B than in groups A, C, and D.
      There were significant differences in inflammatory cell number, pouch membrane
      thickness, bone collagen loss, and osteoclast content between group B and groups
      A, C, and D (P < 0.05). CONCLUSION: RANKL antibody can directly block RANKL/RANK
      signal pathway, which is an efficient therapy to inhibit bone absorption
      associated with implant wearing particles.

PMID- 21735776
TI  - [Experimental study on promoting bone consolidation by using platelet-rich plasma
      and decalcified bone matrix during distraction osteogenesis].
AB  - OBJECTIVE: To investigate whether combining use of platelet-rich plasma (PRP) and
      decalcified bone matrix (DBM) has synergistic action on promoting bone
      consolidation and healing. METHODS: Forty male New Zealand rabbits (weighing 2.2
      2.8 kg) were randomly divided into 4 groups (n = 10). The whole blood was
      extracted from the central aural artery and PRP was prepared with the
      Landesberg's method. An 1 cm-defect was made below the tibiofibular joint of the
      left tibia through osteotomy. In group A, defect was repaired by distraction
      osteogenesis (1 cm); in group B, defect was repaired with 0.5 cm DBM and then by
      distraction osteogenesis (0.5 cm); in group C, defect was repaired by distraction
      osteogenesis (1 cm) and local injection of 1 mL PRP; in group D, defect was
      repaired by 0.5 cm DBM combined with 1 mL PRP and then by distraction
      osteogenesis (0.5 cm). Then lengthening started at 7 days after operation, at a
      rate of 1 mm/day and 0.5 mm every time for 10 days (groups A and C) or for 5 days
      (groups B and D). After the lengthening, the consolidation was performed. The X
      ray films were taken at 0, 12, 17, 27, and 37 days after operation. At 37 days
      after operation, the tibial specimens were harvested for Micro-CT scanning, three
      dimensional reconstruction and biomechanical test. RESULTS: The X-ray films
      showed that new bone formation in groups B and C was obviously better than that
      in groups A and D at 37 days. The bone mineral density (BMD), bone mineral
      content (BMC), and bone volume fraction (BVF) of groups B and C were
      significantly higher than those of groups A and D (P < 0.05); the BMD and BMC of
      group C were significantly higher than those of group B (P < 0.05); the BVF had
      no significant difference between groups B and C (P > 0.05). There was no
      significant difference in BMD, BMC, and BVF between groups A and D (P > 0.05).
      The trabecula number (Tb.N) of group C was significantly more than that of other
      groups (P < 0.05), and the trabecula spacing (Tb.Sp) of group C was significantly
      smaller than that of other groups (P < 0.05), but no significant difference was
      found among other groups (P > 0.05). There was no significant difference in the
      trabecula thickness among 4 groups (P > 0.05). The ultimate angular displacement
      had no significant difference among 4 groups (P > 0.05). The maximum torque of
      groups B and C was significantly higher than that of groups A and D (P < 0.05);
      the maximum torque of group C was significantly higher than that of group B (P <
      0.05); no significant difference was found between groups A and D (P > 0.05).
      CONCLUSION: In the rabbit bone defect/lengthening model, local injection of PRP
      can enhance bone consolidation effectively during consolidation phase. In normal
      distraction rate, DBM can promote bone consolidation during distraction
      osteogenesis. In the early stage of distraction osteogenesis, combining use of
      DBM and PRP can not further promote bone consolidation and healing.

PMID- 21735777
TI  - [In vivo experimental study on antibacterial and osteogenic capabilities of
      hydroxyapatite antimicrobial coating with silver].
AB  - OBJECTIVE: To investigate the antibacterial and osteogenic capabilities in vivo
      of hydroxyapatite (HA)/silver (Ag) coating. METHODS: HA/Ag coating (Ag quality
      percentage was 3%) and HA coating were deposited to external fixator Schanz
      screws. The tibial fracture model was established in right hindlimb of 18 adult
      male Beagle dogs (weighing 15-20 kg). The tibia was stabilized with an external
      fixator and 2 Schanz screws of HA coating at proximal tibia (control group, n =
      18) and HA/Ag coating at distal tibia (experimental group, n = 18), and every
      screw incision was infected with Staphylococcus aureus. Infection in screw holes
      and the changes of bone-screw interface were observed by wound grading and X-ray
      films. RESULTS: In control group, wounds infection became worse with time (chi2 =
      13.492, P = 0.001), while in experimental group, no obvious change was observed
      chi2X = 0.208, P = 0.901). The wound grading of experimental group was
      significantly better than that of the control group at 1, 2, and 3 weeks (P <
      0.05). Laser scanning confocal microscope showed that there was bacterial
      adhesion on the surface of screws in 2 groups, viable bacteria mainly in control
      group and non-viable bacteria mainly in experimental group. The scanning electron
      microscope (SEM) observation results of the fractured sclerous tissue section
      showed that an obvious transparent boundary between screw and bone in control
      group, but no obvious boundary in experimental group. The osseointegration ratios
      were 76.23% +/- 15.54% in control group and 93.42% +/- 5.53% in experimental
      group, showing significant difference ( t = 8.843, P = 0.000). The SEM
      observation showed that HA/Ag coating integrated with new bone and the surface of
      implant was filled with new bone in experimental group; obvious interspace was
      seen between the HA coating and new bone in control group. CONCLUSION: HA/Ag
      coating has good antibacterial and osteogenic capabilities, so it can take
      effects in preventing infection in screw holes and loosening of implants.

PMID- 21735778
TI  - [Research progress in influence of bony structure of glenohumeral joint on
      shoulder joint stability].
AB  - OBJECTIVE: To review the progress in influence of bony structure of glenohumeral
      joint on the shoulder joint stability. METHODS: Recent literature, concerning the
      influence factors of the shoulder joint stability and the action of bony
      structure of the glenohumeral joint in the stability of shoulder joint, was
      extensively reviewed and summarized. RESULTS: The specific factors which the bony
      structure of the glenohumeral joint influences the stability of the shoulder
      joint are the conformity index, the shape of the glenohumeral joint, version
      angle, inclination angle, and head shaft angle, etc. CONCLUSION: Although the
      predecessor's research experience and clinical reports have preliminarily
      determined the relationship between the bony structure of the glenohumeral joint
      and the stability of the shoulder joint, it is necessary to further study in
      various aspects (including anatomy, biomechanics, and clinical practice).

PMID- 21735779
TI  - [Role of microRNAs on regulation of bone and cartilage tissue].
AB  - OBJECTIVE: To review the regulation and mechanism of the microRNAs (miRNAs) in
      the bone and cartilage tissue. METHODS: Recent literature concerning the
      regulation and mechanism of the miRNAs in the bone and cartilage tissue was
      extensively reviewed, summarized, and analyzed. RESULTS: Recently miRNAs is a hot
      topic in the bone and cartilage tissue. More and more materials show its
      important regulatory role in osteogenesis and cartilage growth and regeneration,
      but the definite mechanisms have not been clear yet. CONCLUSION: The study on
      miRNAs of bone and cartilage tissue can provide a new access to understanding the
      degenerative osteoarthritic diseases.

PMID- 21735780
TI  - [Effectiveness analysis of laparoscopic repair of parastomal hernia using CK
      Parastomal patch].
AB  - OBJECTIVE: To summarize the surgical technique and the effectiveness of CK
      Parastomal patch in laparoscopic repair of parastomal hernia. METHODS: The
      clinical data were retrospectively analysed from 24 patients who received
      laparoscopic repair of parastomal hernia using CK Parastomal patch between June
      2006 and March 2010. There were 15 males and 9 females with a median age of 55
      years (range, 47-80 years). Among them, 19 patients were with colon parastomal
      hernia in the left lower quadrant and 5 patients with ileum parastomal hernia in
      the right lower quadrant. The parastomal hernia duration was 1 to 4 years (mean,
      2.4 years). The maximal diameter of the hernia ring was 3 to 7 cm (mean, 5.2 cm).
      All patients did not receive hernia repair. RESULTS: Laparoscopic repair of
      parastomal hernia was successfully performed in 18 cases, and open repair was
      used in 6 cases because of extensive adhesion. The average operating time was 121
      minutes (range, 78 to 178 minutes). All wounds healed by first intention. Wound
      seroma occurred in 8 cases at 3 to 7 days after operation and disappeared by
      aspiration. Eleven patients complained of pain in the operative area within 1
      month after operation and it disappeared without intervention. All patients were
      followed up 6 to 39 months (mean, 27 months). One recurrence occurred at 3 months
      after operation, and no recurrence occurred in the other patients. CONCLUSION:
      Laparoscopic repair of parastomal hernia using CK Parastomal patch is a safe and
      feasible procedure with a satisfactory short-term effectiveness, but the long
      term effectiveness should be further observed.

PMID- 21735781
TI  - [Comparison of three composite patches for repair of abdominal wall defect in
      rats under contaminated environment].
AB  - OBJECTIVE: To observe the anti-adhesion and repair effect of 3 composite patches
      which composed of polylactide-co-caprolactone (PLC), hyaluronic acid (HA),
      collagen, and polypropylene (PP) mesh repairing abdominal wall defect in rats
      under contaminated environment, and to investigate the characteristics of 3
      composite patches and the feasibility of one-stage repair. METHODS: Ninety-three
      adult male Wistar rats (weighing 150-250 g) were randomly divided into 3 groups
      (n = 31): PP/PLC composite patches (group A), PP/HA/PLC composite patches (group
      B), and PP/collagen/PLC composite patches (group C). One rat was selected from
      each group to prepare the contaminated homogenate of the small intestine. The
      abdominal wall defect models (1 cm in diameter) were established in other rats,
      and the defects were repaired with 3 composite patches (1.5 cm in diameter)
      according to grouping method. At 30, 60, and 90 days postoperatively, the
      adhesions was observed, and the patch and adjacent tissue was harvested for
      histological observation. RESULTS: Six rats died at 10-70 days postoperatively (2
      in group A, 3 in group B, and 1 in group C). No wound infection, intestinal
      obstruction, or hernia occurred in 3 groups. Adhesion was observed between
      abdominal viscera and the patch, especially intestine, epiploon, and liver.
      According to the modified Katada criteria, no significant difference in the
      adhesion score was found among 3 groups at 30 and 60 days (P > 0.05); the
      adhesion score was significantly lower in group C than in groups A and B at 90
      days (P < 0.05). The histological results showed that inflammatory cell
      infiltration, fibroblasts, secreted collagen, and the residual absorbable
      material were observed around the patch at 30 days in 3 groups. Decreased
      inflammatory cell infiltration, increased fibroblasts and residual PLC were
      observed at 60 days in 3 groups. At 90 days, the fibroblasts became increasingly
      mature, collagen deposited, the mesothelium formed gradually, and the residual
      PLC decreased. CONCLUSION: In contaminated environment, PP/collagen/PLC composite
      patch is superior to PP/PLC and PP/HA/ PLC composite patches in aspect of
      abdominal adhesion and inflammatory reaction, and it is more applicable to one
      stage repair of rat abdominal wall defect. But it is necessary to further study
      in the long-term efficacy and the security of the composite patch.

PMID- 21735782
TI  - [Preliminary experimental study on intrauterine abdominal wall defect repair of
      fetal lamb at late pregnancy].
AB  - OBJECTIVE: To evaluate the feasibility of intrauterine abdominal wall defect
      repair of fetal lamb at late pregnancy. METHODS: Eight healthy pregnant ewes at
      110-115 days of gestation (weighing 14-22 kg) were randomly divided into 2
      groups. In group A (n = 3), the abdominal wall defect of 5 cm x 1 cm was made in
      the fetal lambs, then was closed by strengthening suture; in group B (n = 5), the
      abdominal wall defect of 5 cm x 2 cm was made in the fetal lambs, then was
      repaired by 2 layers of biological patches. After the lambs delivered naturally,
      the lambs and their wounds were observed; at 10th day after birth, the scars were
      harvested for biomechanical and histological observations. RESULTS: One ewe of
      group A and 2 ewes of group B aborted, while the others were successfully
      delivered. In group A, the abdominal incisions of 2 lambs healed well with a line
      like scar and mild intra-abdominal adhesion, and the scar thickness was 4-5 mm.
      In group B, the abdominal incisions of 3 lambs did not heal completely with minor
      intra-abdominal adhesions, and the scar thickness was 3-4 mm. The wound breaking
      strength was 16, 20 N in group A and 10, 14, and 18 N in group B, respectively. A
      slight scar was seen in group A; skin ulcer and underlying fibrous connective
      tissue with inflammatory cell infiltration were seen in group B. CONCLUSION: It
      was feasible to repair the abdominal wall defect of fetal lamb at late pregnancy
      in uterine. Small abdominal wall defect can be sutured directly; biological patch
      can be used to repair larger abdominal wall defect.

PMID- 21735783
TI  - [A comparative study between Coflex interspinous dynamic reconstruction and
      lumbar 360 degrees fusion in treating single-level degenerative lumbar spinal
      disorders].
AB  - OBJECTIVE: To compare the effectiveness and radiological changes of posterior
      decompression combined with Coflex interspinous dynamic reconstruction or lumbar
      360 degrees fusion for degenerative lumbar spinal disorders at L4, 5. METHODS:
      Between October 2008 and November 2010, a comparative study was carried out on
      patients with degenerative lumbar spinal disorders at L4, 5. In group A, 29
      patients underwent posterior decompression combined with Coflex interspinous
      dynamic reconstruction; there were 20 males and 9 females with an average age of
      45.1 years (range, 21-67 years); and the disease duration was 2 months to 4
      years. In group B, 31 patients underwent posterior decompression combined with
      lumbar 360 degrees fusion treatment; there were 16 males and 15 females with an
      average age of 56.2 years (range, 32-86 years); and the disease duration was 3
      months to 6 years. Except the age, there was no significant difference in gender,
      disease duration, and etiology etc. between 2 groups (P > 0.05). The results were
      assessed by Japanese Orthopaedic Association (JOA), visual analogue scale (VAS)
      scores, and Oswestry disability index (ODI). The range of motion (ROM) and
      intervertebral height of affected and adjacent segments, and the ROM of lumbar
      were measured before operation and last follow-up. RESULTS: Significant
      differences were found in the operative time and blood loss between 2 groups (P <
      0.05). Intraoperative dural tear occurred in 1 case of group B, spinal canal
      venous plexus hemorrhage in 1 case of group B, and postoperative cerebrospinal
      fluid leakage in 2 cases of group A and B respectively, showing no significant
      difference (chi2 = 0.119, P = 0.731). The follow-up was 12-21 months in group A
      and was 12-23 months in group B. At the last follow-up, the JOA, VAS scores, and
      ODI of groups A and B were significantly improved when compared with the
      preoperative values (P < 0.05). The VAS score of group A was significantly higher
      than that of group B (P < 0.05). There was no significant difference in the
      intervertebral height of L4, 5 and L5, S1 of groups A and B between pre- and post
      operation (P > 0.05). In group B, the intervertebral height of L3, 4 was
      significantly reduced (P < 0.05) compared with the preoperative one. There was no
      significant difference in the ROM of L5, S1 and ROM of lumbar in groups A and B
      between pre- and post-operation (P > 0.05). At last follow-up, the ROM of L4, 5
      was significantly reduced in group A (P < 0.05), and the ROM of L3, 4 was
      significantly increased in group B (P < 0.05). Except significant differences in
      the intervertebral height and ROM of L3, 4 between 2 groups (P < 0.05), no
      significant difference was found in other parameters (P > 0.05). CONCLUSION:
      Posterior decompression combined with Coflex interspinous dynamic reconstruction
      has the same effectiveness as lumbar 360 degrees fusion in treating degenerative
      lumbar spinal disorders at L4, 5, but the former has a protective effect on the
      adjacent segments of fusion and is recommended for initial treatment of young
      adults and the elderly and frail patients with recurrent.

PMID- 21735784
TI  - [Protective effect of olfactory ensheathing cells in combination with intrathecal
      injection of vascular endothelial growth factor on injured spinal cord in rats].
AB  - OBJECTIVE: To investigate the synergistic effect of a combination of grafted
      olfactory ensheathing cells (OECs) from the olfactory bulbs and intrathecal
      injection of vascular endothelial growth factor (VEGF) on repairing spinal cord
      injury, and to explore the neuroprotection on both neurons and nerve fibers.
      METHODS: OECs from neonatal rats were cultured, purified, and collected with
      0.25% trypsin after 9 days. A total of 75 adult female Wistar rats (weighing 200
      250 g) were randomly divided into 5 groups: group A was sham-surgery group
      receiving laminectomy; the spinal cord injury model was established with weight
      dropped apparatus in the rats of groups B, C, D, and E. Then group B was injected
      with 10 microL DMEM-F12 medium without serum at injury site on the 1 day and was
      intrathecally administrated with 10 microL saline solution twice a day during the
      following 1 week; group C was injected with 10 microL DMEM-F12 medium and 25 ng
      recombined rat VEGF165 (rrVEGF165); group D was injected with 10 microL DMEM-F12
      medium containing 1 x 10(5) OECs and 10 microL saline solution; group E was
      injected with 10 microL DMEM-F12 medium containing 1 x 10(5) OECs and 25 ng
      rrVEGF165. The functional recovery of hindlimb was evaluated by the Basso-Beattie
      Bresnahan (BBB) score at 1 day and each week from 1 to 8 weeks. The histological
      changes and the changes of ultrastructure were observed at 8 weeks after
      operation by HE and electron microscope, and the immunohistochemistry staining
      was used for p75 nerve growth factor receptor (p75NGFR), Caspase-3, and von
      Willebrand factor (vWF). RESULTS: The function of hindlimb recovered rapidly in
      group E; the BBB score reached the peak at 8 weeks, and it was significantly
      higher than those in other groups (P < 0.05). The histology and ultrastructure
      observation showed that nerve fibers and neurons were damaged seriously in group
      B, moderately in groups C and D, and slightly in group E. Numerous spared tissue
      between nerve stumps, fibers with regular myelination, and neurons with little
      vacuolar mitochondria were observed in group E. The immunohistochemistry staining
      revealed that Caspase-3 positive cells in groups B, C, D, and E were
      significantly more than that in group A (P < 0.05); more Caspase-3 positive cells
      were found in groups B and D than in groups C and E (P < 0.05), while no
      significant difference was found between groups C and E (P > 0.05). And more
      vessels per high field were examined in groups C and E than in groups A, B, and D
      (P < 0.05), while no significant difference was found between groups C and E (P >
      0.05). The p75NGFR positive results showed the survival of OECs in groups D and E
      at 8 weeks after OECs transplantation. CONCLUSION: Grafted OECs combined with
      intrathecal injection of VEGF has significant promotive effects on restoration of
      spinal cord injury in rats, can improve part function of nerve fibers, and shows
      neuroprotection on damaged cells and fibers, which have a synergistic effect.

PMID- 21735785
TI  - [Establishment of tractive spinal cord injury model in rats with a novel spinal
      distractor].
AB  - OBJECTIVE: To develop a tractive spinal cord injury model in rats with a novel
      spinal distractor so as to supply the reliable animal model for researching the
      pathological mechanism and rehabilitation treatment of tractive spinal cord
      injury. METHODS: A novel spinal distractor was prepared based on previous study.
      Sixty adult Sprague Dawley rats (weighing 250-300 g) were randomly divided into 5
      groups, 12 rats in each group. T12-L3 spinal structures in the rear area were
      exposed and then T13-L2 spinal cords were revealed via dual laminectomy and kept
      integrity. In group A, a novel spinal distractor was placed without distraction;
      in groups B, C, D, and E, the T12-L3 spines were traced with a novel spinal
      distractor which put on transverse process of T12-L3 vertebrae. During the
      tractive period, the somatosensory evoked potential (SEP) was used to monitor
      spinal cord function. The SEP amplitudes descended 50% and kept distracting for 5
      minutes in group B and for 10 minutes in group C, and descended 70% and kept
      distracting for 5 minutes in group D and for 10 minutes in group E, respectively
      to establish the tractive spinal cord injury model of T11-L2. The improved
      combine behavioral score (ICBS) was recorded at 1 and 7 days after injury in 6
      rats of each group. The T13-L2 spinal tissue specimens were harvested for the
      morphological observation by HE and Nissl's staining and for neurons counting.
      RESULTS: In group A, the ICBS score was 0 at 1 and 7 days after operation,
      showing significant difference when compared with the scores of the other groups
      (P < 0.05). The ICBS scores of groups D and E were significantly higher than
      those of groups B and C (P < 0.05). Edema and hemorrhage were observed in spinal
      cord surface and normal morphological structures were destroyed at different
      extent in groups B, C, D, and E at 1 day. There were adherence and congestion
      between spinal cord surface and peripheral issue without luster at 7 days, and
      dura depression was observed at the injury section, especially in group E.
      Necrosis and dissolution occurred in some neurons, and Nissl body structure
      dissolved or disappeared in groups B, C, D, and E. The neuron counting gradually
      decreased in accordance with the aggravation of injury in groups B, C, D, and E,
      showing significant difference when compared with group A (P < 0.05). Significant
      differences in neuron counting were found among groups B, C, D, and E (P < 0.05).
      CONCLUSION: The tractive spinal cord injury model in rats can be successfully
      established with novel spinal distractor, and the model established by SEP
      amplitude descending 70% and keeping distracting for 10 minutes is more suitable
      for study in tractive spinal cord injury.

PMID- 21735786
TI  - [Effect of local basic fibroblast growth factor and 5-fluorouracil on
      accelerating healing and preventing tendon adhesion after flexor tendon repair].
AB  - OBJECTIVE: To assess the effect of basic fibroblast growth factor (bFGF) and 5
      fluorouracil (5-FU) applied topically on the tendon adhesion and the healing
      process after the flexor tendon repair in Leghorn chickens. METHODS: Ninety male
      Leghorn chickens (weighing 3.0-3.5 kg) were randomly divided into 3 groups, with
      30 chickens in each group. The flexor digitorum profundus tendons of the third
      right toes were transected and sutured directly. The repair site in group A was
      given 0.6 microL fibrin sealant (FS). In group B, the repair site was given 0.6
      microL FS containing 500 ng bFGF. In group C, before the tendons were transected,
      they had been soaked in 5-FU solution, and then the same treatment as group B was
      given. Six specimens of the third toe were harvested to perform the macroscopical
      and histological examinations at 1, 2, 4, and 8 weeks, respectively, and to
      perform the biomechanical test at 8 weeks. RESULTS: All animals survived until
      the experiment was completed. All incisions healed smoothly. No rupture occurred
      in the repaired tendon. At 8 weeks, the adhesion degree was lighter in group C
      than in group B (P < 0.05), but there was no significant difference in the
      adhesion degree between group A and groups B, C (P > 0.05). At 1, 2, and 4 weeks
      after operation, the number of fibroblast cells of group A was significantly less
      than that of group B (P < 0.05), and the number of fibroblast cells of group C
      was significantly less than that of group A and group B in the tendon sheath and
      epitenon (P < 0.05); however, it was significantly more than that of group A in
      the tendon parenchyma (P < 0.05), and no significant difference was observed when
      compared with that of group B (P > 0.05). At 8 weeks, no difference was found
      among 3 groups (P > 0.05). The collagen fiber content of group A was
      significantly less than that of group B at 4 and 8 weeks (P < 0.05). In the
      sheath and epitenon, the collagen fiber content of group A was significantly more
      than that of group C at 4 weeks (P < 0.05); however, no significant difference
      was found between 2 groups at 8 weeks (P > 0.05). The collagen fiber content of
      group A was significantly less than that of group C in the parenchyma at 4 and 8
      weeks (P < 0.05). At all time points, the collagen fiber content of group B was
      significantly more than that of group C in the sheath and epitenon (P < 0.05),
      but no significant difference in the parenchyma was observed between 2 groups (P
      > 0.05). The biomechanical tests showed that the gliding excursion of the tendon
      in groups A, B, and C was (3.51 +/- 0.56), (2.84 +/- 0.42), and (4.56 +/- 0.59)
      mm, respectively; the work of flexion was (14.08 +/- 1.85), (20.62 +/- 3.52), and
      (10.91 +/- 1.53) N x mm, respectively; and the ultimate tensile strength of the
      tendon was (11.26 +/- 1.83), (15.02 +/-2.20), and (14.40 +/- 1.57) N,
      respectively. There were significant differences in the gliding excursion of the
      tendon and the work of flexion among 3 groups (P < 0.05) and in the ultimate
      tensile strength of the tendon between group A and groups B, C (P < 0.05), but
      there was no significant difference in the ultimate tensile strength of the
      tendon between group B and group C (P > 0.05). CONCLUSION: Local single-use bFGF
      and 5-FU can not only effectively promote the healing of flexor tendon, but also
      significantly reduce tendon adhesion.

PMID- 21735787
TI  - [Effect of Col I A1 antisense oligodeoxynucleotide on collagen synthesis in human
      hypertrophic scar transplanted nude mouse model].
AB  - Objective Col I A1 antisense oligodeoxynucleotide (ASODN) has inhibitory effect
      on collagen synthesis in cultured human hypertrophic scar fibroblasts. To
      investigate the effects of intralesional injection of Col I A1 ASODN on collagen
      synthesis in human hypertrophic scar transplanted nude mouse model. METHODS: The
      animal model of human hypertrophic scar transplantation was established in the 60
      BALB/c-nunu nude mice (specific pathogen free grade, weighing about 20 g, and
      aged 6-8 weeks) by transplanting hypertrophic scar without epidermis donated by
      the patients into the interscapular subcutaneous region on the back, with 1 piece
      each mouse. Fifty-eight succeed models mice were randomly divided into 3 groups
      in accordance with the contents of injection. In group A (n = 20): 5 microL Col I
      A1 ASODN (3 mmol/L), 3 microL liposome, and 92 microL Opti-MEM I; in group B (n =
      20): 3 microL liposome and 97 microL Opti-MEM I; in group C (n = 18): only 100
      microL Opti-MEM I. The injection was every day in the first 2 weeks and once
      every other day thereafter. The scar specimens were harvested at 2, 4, and 6
      weeks after injection, respectively and the hardness of the scar tissue was
      measured. The collagens type I and III in the scar were observed under polarized
      light microscope after sirius red staining. The ultrastructures of the scar
      tissues were also observed under transmission electronic microscope (TEM).
      Additionally, the Col I A1 mRNAs expression was determined by RT-PCR and the
      concentrations of Col I A1 protein were measured with ELISA method. RESULTS:
      Seventeen mice died after intralesional injection. Totally 40 specimens out of 41
      mice were suitable for nucleic acid and protein study, including 14 in group A,
      13 in group B, and 14 in group C. The hardness of scars showed no significant
      difference (P > 0.05) among 3 groups at 2 weeks after injection, whereas the
      hardness of scars in group A was significantly lower than those in groups B and C
      at 4 and 6 weeks (P < 0.05), and there was no significant difference between
      groups B and C (P > 0.05). The collagen staining showed the increase of collagen
      type III in all groups, especially in group A with a regular arrangement of
      collagen type I fibers. TEM observation indicated that there was degeneration of
      fibroblasts and better organization of collagen fibers in group A, and the
      structures of collagen fibers in all groups became orderly with time. The
      relative expressions of Col I A1 mRNA and the concentrations of Col I A1 protein
      at 2 and 4 weeks after injection were significant difference among 3 groups (P <
      0.05), and they were significantly lower in group A than in groups B and C (P <
      0.05) at 6 weeks after injection, but no significant difference was found between
      groups B and C (P > 0.05). CONCLUSION: Intralesional injection of Col I A1 ASODN
      in the nude mice model with human hypertrophic scars can inhibit the expression
      of Col I A1 mRNA and collagen type I, which enhances the mature and softening of
      the scar tissue. In this process, liposome shows some assistant effect.

PMID- 21735788
TI  - [Complication after selective arterial embolization in internal iliac artery and
      median sacral artery with gelfoam particle in dogs].
AB  - OBJECTIVE: To observe the complication after embolizing the bilateral internal
      iliac arteries and the median sacral artery of dogs by different combinations and
      embolization levels with gelfoam particle, and to provide a reference for safety
      application of gelfoam in clinic. METHODS: Sixteen common grade adult healthy
      dogs (weighing 10-13 kg, 14 males and 2 females) were randomly divided into 5
      groups. Under the monitoring of digital subtraction angiography (DSA), the
      embolization was performed with gelfoam particle (diameter, 50-150 microm) in
      bilateral internal iliac arteries and the main branch of the median sacral artery
      (group A, n = 3), in bilateral internal iliac arteries and the first branch of
      the median sacral artery (group B, n = 3), in the main branch of bilateral
      internal iliac arteries (group C, n = 3), in the unilateral internal iliac artery
      and the main branch of the median sacral artery (group D, n = 4), and in the main
      branch of unilateral internal iliac artery (group E, n = 3). Under the DSA, the
      anatomic relationships of the abdominal aorta, bilateral external iliac arteries,
      bilateral internal iliac arteries, and median sacral artery were observed before
      embolization. The survival dogs were observed and the specimens of bladder,
      rectum, sciatic nerve, and gluteal muscles were harvested for the general and
      histological observations at 3 days after embolization. RESULTS: In dogs, there
      was no common iliac artery; bilateral external iliac arteries originated from the
      abdominal aorta and the starting of the median sacral artery had variation. Seven
      dogs (3 in group A, 3 in group C, and 1 in group D) died within 2 days after
      embolization, and the others survived to the end of the experiment. In the dead
      dogs of groups A, C, and D, the darkening and necrosis of the rectum were
      observed; the bladder presented lamellar obfuscation and focal hemorrhage and
      edema; and the median urinary volume in bladder was 270.6 mL. In survival dogs,
      no obvious change was observed in the rectum; the bladder only manifested light
      edema; and the median urinary volume in bladder was 137.0, 220.5, and 28.0 mL,
      respectively in groups B, D, and E. The rectum and bladder of dead dogs in groups
      A, C, and D manifested the disrupted cells, generous inflammatory cells
      infiltration, and desquamation of epithelial cells; the rectum and bladder of
      survival dogs in groups B, D, and E manifested light inflammatory cells
      infiltration and edema; the embolized artery mainly focused on the arterioles
      whose diameter was 100-200 microm. The sciatic nerve and gluteal muscles of each
      group had no obvious change except for light edema. CONCLUSION: When the internal
      iliac artery and median sacral artery are embolized with gelfoam particle with a
      diameter of 50-150 microm, to ensure the safeness of pelvic organs, the embolized
      artery can not exceed the first branch when the 3 arteries are embolized at the
      same time, or reserve at least unilateral internal iliac artery when embolized to
      the trunk, or it will result in pelvic organ necrosis and perforation.

PMID- 21735789
TI  - [Comparison of effect between vascularization osteogenesis and membrane guided
      osteogenesis in bone repair by tissue engineered bone with pedicled fascial flap
      packing autologous red bone marrow].
AB  - OBJECTIVE: To compare the effect between vascularization osteogenesis and
      membrane guided osteogenesis in the bone repair by the tissue engineered bone
      with pedicled fascial flap packing autologous red bone marrow (ARBM), so as to
      provide a reference for the bone defect repair in clinic. METHODS: The tissue
      engineered bone was constructed with ARBM and the osteoinductive absorbing
      recombinant human materials with recombinant human bone morphogenetic protein 2.
      Sixty New Zealand rabbits (aged 4-5 months, weighing 2.0-2.5 kg) were randomly
      divided into group A (n = 16), group B (n = 22), and group C (n = 22). The
      complete periosteum defect model of 1.5 cm in length was prepared in right ulnar
      bone, then the tissue engineered bone was implanted in the bone defect area in
      group A, the tissue engineered bone with free fascial flap in group B, and the
      tissue engineered bone with pedicled fascial flap in group C. At 4, 8, 12, and 16
      weeks, the tissue of bone defect area was harvested from 4 rabbits of each group
      for the general, histological, and immunohistochemical staining observations; at
      8, 12, and 16 weeks, 2 rabbits of groups B and C, respectively were selected to
      perform ink perfusion experiment by axillary artery. RESULTS: The general
      observation showed that the periosteum-like tissues formed in the fascial flap of
      groups B and C, chondroid tissues formed in group B, new bone formed in group C,
      and the fibrous and connective tissues in group A at 4 and 8 weeks; a few porosis
      was seen in group A, more new bone in group B, and bone stump formation in group
      C at 12 and 16 weeks. Histological observation showed that there were few new
      blood vessels and new bone trabeculae in groups A and B, while there were large
      amounts of new blood vessels and mature bone trabeculae in group C at 4 and 8
      weeks. There were a few new blood vessels and new bone trabeculae in group A;
      more blood vessels, significantly increased mature trabeculae, and the medullary
      cavity formation in group B; and gradually decreased blood vessels, the mature
      bone structure formation, and the re-opened medullary cavity in group C at 12 and
      16 weeks. The immunohistochemical staining observation showed that the levels of
      CD105, CD34, and factor VIII were higher in group C than in groups A and B at
      different time points. The bone morphometry analysis showed that the trabecular
      volume increased gradually with time in 3 groups after operation; the trabecular
      volume in group C was significantly more than those in groups A and B at
      different time points (P < 0.05); and there was significant difference between
      groups A and B (P < 0.05) except the volume at 4 weeks (P > 0.05). The vascular
      image analysis showed that the vascular regenerative area ratio in group C was
      significantly higher than those in groups A and B at different time points (P <
      0.05). The ink perfusion experiment showed that the osteogenic zone had sparse
      ink area with no obvious change in group B, while the osteogenic zone had more
      intensive ink area and reached the peak at 8 weeks, then decreased in group C.
      CONCLUSION: The tissue engineered bone with pedicled fascial flap packing ARBM
      has the vascularization osteogenesis effect at early stage, but the effect
      disappears at late stage gradually when the membrane guided osteogenesis is main.

PMID- 21735790
TI  - [Effect of combined therapy of granulocyte colony stimulating factor and bone
      marrow mesenchymal stem cells carrying hepatocyte growth factor gene on
      angiogenesis of myocardial infarction in rats].
AB  - OBJECTIVE: To investigate the effect of combined therapy of granulocyte colony
      stimulating factor (G-CSF) and bone marrow mesenchymal stem cells (BMSCs)
      carrying hepatocyte growth factor (HGF) gene on the angiogenesis of myocardial
      infarction (MI) in rats and the mechanisms of the synergistic effect. METHODS:
      BMSCs were aspirated from the femur and tibia of 3-week-old Sprague Dawley (SD)
      male rats. The third generation of BMSCs were harvested and transfected with Ad
      HGF. The MI models were established in 44 SD male rats (weighing 200-250 g) by
      ligating the left coronary artery. At 4 weeks after ligation, the shorting
      fraction (FS) of the left ventricle being below 30% was used as a criteria of
      model success. The BMSCs (5 x 10(7)/mL) transfected with Ad-HGF were transplanted
      into the infarct zone of 12 SD rats, and the expression of HGF protein was
      detected by Western blot method at 2, 7, and 14 days after transplantation. At 4
      weeks, the other 32 SD rats were randomly divided into 4 groups (n = 8). The 0.1
      mL normal saline was injected into the infarct zone in control group; 0.1 mL
      normal saline was injected combined with intraperitoneal injection G-CSF [100
      microg/ (kg x d)] for 5 days in G-CSF group; 0.1 mL BMSCs (5 x 10(7)/mL)
      transfected with Ad-HGF was injected into the infarct zone in HGF group; 0.1 mL
      BMSCs (5 x 10(7)/mL) transfected with Ad-HGF was injected combined with
      intraperitoneal injection G-CSF [100 microg/ (kg x d)] for 5 days in combined
      therapy group. At 2 weeks after transplantation, heart function was detected by
      cardiac ultrasound and hemodynamic analysis, and then myocardial tissue was
      harvested to analyse the angiogenesis of the infarct zone, and the expression of
      VEGF protein by immunofluorescence staining. RESULTS: The expression of HGF
      protein in vivo was detected at 2 days and 7 days of BMSCs transfected with Ad
      HGF transplantation. There was no significant difference in left ventricular
      systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),
      dP/dtmax, and FS between G-CSF group and control group (P > 0.05). When compared
      with the control group, LVEDP decreased significantly; LVSP, FS, and dP/dtmax
      increased significantly (P < 0.05) in HGF group and combined therapy group. When
      compared with HGF group, FS and dP/dtmax increased significantly in combined
      therapy group (P < 0.05). Immunofluorescence staining showed that the vascular
      endothelial cells were observed in myocardial infarction border zone. The
      vascular density and the expression of VEGF protein were significantly higher in
      combined therapy group than in other 3 groups (P < 0.05). CONCLUSION: The
      combined therapy of G-CSF and BMSCs carrying HGF gene has a synergistic effect
      and can enhance infarct zone angiogenesis through inducing the expression of VEGF
      protein.

PMID- 21735791
TI  - [Construction methods of tissue engineered cell sheet].
AB  - OBJECTIVE: To summarize the recent progress of construction methods of engineered
      cell sheet and to forecast the possible prospect. METHODS: The recent original
      articles about investigation and application of engineered cell sheet were
      reviewed. Several common methods were selected and expounded. RESULTS: The
      construction methods of engineered cell sheet mainly include temperature
      responsive culture dish, salmon atelocollagen, magnetic force, surface roughness,
      and polyelectrolytes, which may overcome the limits of traditional tissue
      engineering methods. CONCLUSION: The construction methods of engineered cell
      sheet are feasible and have a bright future in the clinical application.

PMID- 21735792
TI  - [Research progress of biological characteristics and advantages of Wharton's
      jelly-mesenchymal stem cells].
AB  - OBJECTIVE: To summarize the research progress of biological characteristics and
      advantages of Wharton's jelly-mesenchymal stem cells (WJ-MSCs). METHODS: The
      related literature on the biological characteristics of WJ-MSCs, umbilical cord
      blood MSCs (UBMSCs) and bone marrow MSCs (BMSCs) was extensively reviewed and
      analyzed. RESULTS: A large number of MSCs which are able to self-replicate, self
      renew and have high proliferation and multipotent differentiation can be isolated
      from the Wharton's jelly of umbilical cord. WJ-MSCs have many advantages in
      isolation time, isolation efficiency, expansion time, passage capacity, expansion
      capacity when compared with UBMSCs and BMSCs. CONCLUSION: WJ-MSCs have numerous
      advantages of convenient and abundant sources, relatively pure, non-ethical
      issues, and so on, which can be used for cell transplant therapy, gene therapy,
      and the ideal seed cells of building tissue engineered organ, so they provide new
      ideas for tissue regeneration repair and reconstruction.

PMID- 21735793
TI  - [Progress in amputation technique of diabetic foot].
AB  - OBJECTIVE: To review the progress in amputation technique of diabetic foot.
      METHODS: Recent literature concerning the amputation technique of diabetic foot
      was reviewed and analyzed. RESULTS: According to the different levels of the
      amputation, the diabetic foot's amputation can be classified as major amputation
      and minor amputation, and different kinds of methods can derive from these
      styles. Different factors should be considered when the style and method of
      amputation are chosen. CONCLUSION: To the diabetic foot amputation, the general
      rule is to limit the amputation level on the premise of the good clinical effect.
      The health state, the region of the diabetic foot, the tissue perfusion, the
      susceptibility to infection in local tissue, and the ability of wound healing are
      important factors in selecting the styles and methods of diabetes-related
      amputations. Importance should be attached to the synthesis treatments of
      diabetes to prevent the higher level amputation.

PMID- 21735794
TI  - [Research progress of viscosupplementation].
AB  - OBJECTIVE: To carry out a comprehensive and objective evaluation of
      viscosupplementation, so as to provide the actual judgments of effectiveness,
      development trends, and direction. METHODS: The related literature was reviewed,
      and the keys were the assessments from the international relevant advisory bodies
      and insurance companies and the evidence-based medicine on clinic. RESULTS:
      Viscosupplementation has been gradually accepted. Although there are many
      different clinical views of the viscosupplementation in the molecular weight of
      hyaluronan, injection dose, and the indications, intra-articular injection of
      hyaluronan for the treatment of osteoarthritis is well accepted. CONCLUSION:
      Viscosupplementation is one of the methods of treating osteoarthritis. As it has
      been already verified that hyaluronan is effective in treating osteoarthritis of
      the knee and the periarthritis of shoulder, the hip joint injection is gradually
      recognized, and other small joints are going gradually.

PMID- 21735795
TI  - Impact of a quality improvement programme on family planning services in Egypt.
AB  - The Egyptian government's national Gold Star programme to improve the quality and
      usage of family planning was conducted from 1995 to 2000. Data from the 2004
      Egypt Service Provision Assessment survey were used to assess whether the
      certified Gold Star facilities had sustained higher quality services than non
      Gold Star facilities 4 years after conclusion of the programme. A nationally
      representative sample of 637 facilities providing family planning services were
      compared using several quality indicators. Gold Star facilities had significantly
      better availability of family planning methods, counselling and examination
      services than non-Gold Starfacilities, independent of type, size and geographical
      location. Providers in Gold Star facilities were also more likely to adhere to
      higher quality practices in counselling and examination than in non-Gold Star
      facilities. The Gold Star programme was effective and could be implemented
      elsewhere in the region and globally.

PMID- 21735796
TI  - Prevalence, awareness and determinants of contraceptive use in Qatari women.
AB  - We determined the knowledge of, attitude to and practice of contraception and the
      associated sociodemographic factors among a representative sample 1130 Qatari
      married women aged 18-49 years. Data were collected by questionnaire. The mean
      age of the women was 32.5 (SD 7.6) years. The vast majority (94.6%) knew about
      contraception but of these 1070, only 694 (64.9%) were in favour of
      contraception. Knowledge of contraception increased with increasing level of
      education (P < 0.001), but decreased the lower the household income (P = 0.002).
      Only 511 (47.8%) women were currently using contraceptives, which was
      significantly associated with age, husband's age, years of marriage, education
      level, income level and attitude to family planning. The most commonly known and
      used contraceptives were intrauterine device and pills. Friends were the most
      common source of knowledge about family planning method (80.0%).

PMID- 21735797
TI  - Quality of care for obstetric emergencies in 4 general hospitals in Egypt: an
      observational study of delays in receiving care and blood bank services.
AB  - A lack of available blood contributes to 16% of all maternal deaths in Egypt.
      This study aimed to assess the quality of care for obstetric emergencies in 4
      general hospitals in Egypt over a 6-month period with the focus on delays in
      receiving care and blood bank services. Observations were made of the processes
      and delays in the clinical setting, from the start of each patient's complaint
      until discharge, and the receipt and filling of orders for blood at the blood
      bank. Patients failed to recognize danger signs. Lack of transportation,
      incorrect choice of provider or facility and unclear referral systems added
      further delays. Delays occurred in hospital admission, assessment of patients,
      initiation of resuscitation, initiation of medical or surgical interventions,
      ordering blood, J receipt of blood and administration of blood to patients. The
      blood ordering procedures were substandard. Lack of blood availability had
      multidisciplinary causes.

PMID- 21735798
TI  - Needlestick injuries among health care workers of University of Alexandria
      Hospitals.
AB  - The aims of this cross-sectional study were to investigate the prevalence and
      circumstances of needlestick injury (NSI) among heath care workers at University
      of Alexandria teaching hospitals and to assess the effectiveness of the existing
      control measures and standard precautions. Data were obtained by anonymous, self
      reporting questionnaire from 645 nurses, physicians and ancillary staff in 2007.
      Around two-thirds of workers (67.9%) had suffered at least 1 NSI in the last 12
      months. High-risk patients (with history of HIV, hepatitis B virus or, hepatitis
      C virus infection or injecting drug use) were involved in 8.2% of injuries. On
      evaluating the effectiveness of existing control measures, significant protective
      factors against NSI were: using devices with safety features (OR 0.41), adherence
      to infection control guidelines (OR 0.42), training in injection safety (OR
      0.14), comfortable room temperature (OR 0.32) and availability of a written
      protocol for prompt reporting (OR 0.37).

PMID- 21735799
TI  - Nutritional status of children hospitalized in Tabriz Paediatric Hospital,
      Islamic Republic of Iran, 2008.
AB  - This study aimed to evaluate the nutritional status of children consecutively
      admitted as inpatients to Tabriz Paediatric Hospital in the north-west of the
      Islamic Republic of Iran between June and August 2008. A total of 140 children
      aged 2-12 years were included. Patients' weight, height and triceps skinfold
      thickness (TSFT) were measured, and nutritional status was evaluated. Evaluation
      of weight-for-age, height-for-age, weight-for-height and TSFT showed that 48.6%,
      30.7%, 32.2% and 14.3% of the patients, respectively, were malnourished.
      Malnutrition among hospitalized children is worthy of attention, and effective
      strategies for systematic screening and treatment of malnutrition need to be
      developed and implemented.

PMID- 21735800
TI  - Profile of drug users in Karachi City, Pakistan.
AB  - Drug use has been identified as a major public issue in Pakistan. A descriptive
      questionnaire survey in Karachi city was made to identify the socioeconomic
      profile and beliefs and practices of 500 drug users The most commonly used drugs
      were cocaine (19.0%) and crack-cocaine (15.0%), followed by amphetamine, (11.0%),
      alcohol, caffeine, barbiturates and benzodiazepines (10.0% each). Key
      psychological factors leading tc drug use were problems with parental or marital
      relations or break-up of a relationship (45.0%). Drugs were seer as an escape
      from stressful life events (28.0%) or feelings of failure (18.2%). Many drug
      users blamed the origin of their drug use on bad social influences (47.0%) or
      socioeconomic problems (23.4%). Preventive measures are needed to decrease the
      rate of drug addiction in Karachi.

PMID- 21735801
TI  - Type-D personality: a predictor of quality of life and coronary heart disease.
AB  - The present study examined the association oftype-D personality (and its
      components) with quality of life in cardiac patients compared with healthy
      people. A sample of 80 patients with myocardial infarction (MI) and 70 healthy
      people aged 45-60 years completed the WHO quality of life brief questionnaire and
      the 14-item type-D personality scale. A significantly higher percentage of the MI
      group scored positive for type-D personality compared with healthy individuals
      (71% versus 33%). Significantly more MI patients had low quality of life scores
      than did healthy individuals (64% versus 20%). Regression analysis showed that
      higher scores on type-D personality had a negative impact on quality of life in
      MI patients and that the social inhibition component had a greater impact than
      negative affectivity. Psychological assessment for type-D personality may be
      helpful in developing health care plans.

PMID- 21735802
TI  - Comparison of microscopical examination and semi-nested multiplex polymerase
      chain reaction in diagnosis of Plasmodium falciparum and P. vivax.
AB  - We compared light microscopy examination and a semi-nested multiplex PCR (SnM
      PCR) assay in endemic areas of the Islamic Republic of Iran. A total of 68
      individuals with malaria-positive and suspected malaria symptoms were included in
      the study. Giemsa-stained thick blood films were examined under a light
      microscope for malaria parasites in 100 and 200 fields. DNA was extracted from
      blood samples and SnM-PCR based on the amplification of the small sub-unit
      ribosomal RNA (ssrRNA) gene sequences was applied. Microscopical examination
      showed that 48.5% (33.8% P. vivax and 14.7% P.falciparum) and 50% (35.3% P. vivax
      and 14.7% P. falciparum) of the samples were positive in 100 and 200 fields
      respectively. SnM-PCR showed the same results as the 200 field microscopy.

PMID- 21735803
TI  - [Prevalence of metabolic syndrome in chronic haemodialysis patients in Morocco].
AB  - We determined the prevalence of metabolic syndrome in 25 chronic haemodialysis
      patients in the haemodialysis centre of the Mohammed V military teaching hospital
      in Rabat. The mean age of the patient as was 46.5 (SD 14.8) years and mean
      haemodialysis duration 62.9 (SD 38.4) months. We evaluated the 5 parameters of
      metabolic syndrome: waist circumference, hypertriglyceridaemia, high-density
      lipoprotein (HDL) cholesterol, blood pressure and blood glucose. In all, 11 (44%)
      patients had metabolic syndrome: 7 women and 4 men. Low HDL cholesterol was found
      in 100% of the patients, hypertriglyceridaemia in 90.9% and hypertension in
      63.6%. There were significant differences between patients with and without
      metabolic syndrome with regard to levels of hypertriglyceridaemia and HDL
      cholesterol, and waist circumference. Factors significantly associated with the
      presence of metabolic syndrome were abdominal obesity, and systolic hypertension
      and aypertriglyceri daemia.

PMID- 21735804
TI  - Adaptation of the school health index to assess the healthy school environment in
      Jordan.
AB  - When the Jordan Ministry of Education planned workshops to raise teachers'
      awareness of the health environment in schools in underdeveloped governorates, a
      pre-post intervention study assessed the impact of these workshops in changing
      teachers' perceptions. A total of 193 teachers completed the self-administered
      Centers for Disease Control and Prevention school health index (SHI) for
      elementary schools, adapted for this setting using 6 of the 8 original modules.
      After the workshops, teachers' mean scores on all modules improved significantly,
      from 49.5% to 55.9% for health and safety/environment policies; 44.2% to 56.5%
      for health education; 40.3% to 52.9% for physical education; 51.3% to 59.2% for
      nutrition services; 62.5% to 73.8% for health services; and 55.2% to 68.3% for
      family/community involvement. The SHI model is implementable in a developing
      country

PMID- 21735805
TI  - [Evaluation of preventive care in the dentistry department clinics of the
      University Cheikh Anta Diop in Dakar].
AB  - This was a cross-sectional study of 295 patients treated by dentistry students
      that aimed to evaluate the preventive care received by patients attending clinics
      of the dentistry department of the University Cheikh Anta Diop in Dakar. The
      sociodemographic characteristics of the patients, clinic specialty, patients'
      brushing technique and the other preventive care was recorded. The study sample
      comprised 48.5% men and 76.6% adults. Over 32% of the patients were from the
      conservative dentistry clinic. For 52.2% of the patients, no preventive action
      was provided. The use of visual aids when teaching oral hygen ne was observed for
      17.4% of cases. Attitudes and practices of the dentistry students in relation to
      care require more vigilance and emphasis on prevention.

PMID- 21735806
TI  - Specialty choices of medical students and house officers in Karachi, Pakistan.
AB  - Unerstanding patterns of career choices inmedicine is importnat for educators and
      policy-makers to plan the supply of specialists. This study analysed the career
      choices made by medical students and house officers in 2 private and 2 public
      medical schools in Karachi, Pakistan. An anonymous, self-administered and
      gynaecology were the 4 highest ranked specialties, with internal medicine ranked
      top as both the 1st and 2nd choice. Internal medicine was the 1st choice for
      significantly more students in public than private medical colleges (22.2% versus
      1l4.9%). Students from private medical institutions chose a wider range of
      specialties than those from publicly-funded colleges. A high proportion of
      medical students and graduates in Karachi favour the same medical specialties,
      which may lead to saturation in those areas of specialization.

PMID- 21735807
TI  - Team building. ASHE recognizes the top in facilities collaboration.

PMID- 21735808
TI  - Calling all nurses. Selecting the right communication system.

PMID- 21735810
TI  - Flawless furnishings. Health care furniture makers stress cleanability.

PMID- 21735809
TI  - Facility checkup: conducting a health care building assessment.

PMID- 21735811
TI  - Commissioning is key to return on investment.

PMID- 21735812
TI  - Seeking your input for future planning.

PMID- 21735813
TI  - The future is now. How 10 forces are changing health care design.

PMID- 21735814
TI  - Tread lightly. Maintaining a durable and attractive hospital floor.

PMID- 21735815
TI  - [Britton Chance (1913-2010)--from sailing to biophysics and biochemistry and
      back].
AB  - A short CV of Britton Chance, an outstanding American biophysicist and
      biochemists, who has passed away in November 2010, is presented. Chance invented
      and applied in biochemical research fast recording of difference spectra during
      chemical reactions. Due to this technique he discovered and studied formation of
      enzyme-substrate complexes as exemplified by the peroxidase reaction. He also
      described spectral changes of electron carriers of mitochondrial respiratory
      chain that accompany transition from the resting to the active (phosphorylating)
      states. Applying vibrating platinum electrode, he recorded changes in the rate of
      oxygen uptake by isolated mitochondria in resting and phosphorylating states and
      defined the so-called respiratory states, called after his name. He was the first
      to describe formation of reactive oxygen species by mitochondria. Britton Chance
      was a devoted yachtsman and won a gold medal for the United States in sailing at
      the 1952 Olympic Games in Helsinki.

PMID- 21735816
TI  - [DNA computing].
AB  - Biocomputers can be an alternative for traditional "silicon-based" computers,
      which continuous development may be limited due to further miniaturization
      (imposed by the Heisenberg Uncertainty Principle) and increasing the amount of
      information between the central processing unit and the main memory (von Neuman
      bottleneck). The idea of DNA computing came true for the first time in 1994, when
      Adleman solved the Hamiltonian Path Problem using short DNA oligomers and DNA
      ligase. In the early 2000s a series of biocomputer models was presented with a
      seminal work of Shapiro and his colleguas who presented molecular 2 state finite
      automaton, in which the restriction enzyme, FokI, constituted hardware and short
      DNA oligomers were software as well as input/output signals. DNA molecules
      provided also energy for this machine. DNA computing can be exploited in many
      applications, from study on the gene expression pattern to diagnosis and therapy
      of cancer. The idea of DNA computing is still in progress in research both in
      vitro and in vivo and at least promising results of these research allow to have
      a hope for a breakthrough in the computer science.

PMID- 21735817
TI  - [Cytosine methylation in DNA and its role in cancer therapy].
AB  - DNA methyltransferase 1 (DNMT1) is one of three enzymes independently coded in
      mammalian cells. It catalyses postreplicative synthesis of 5-methylcytosine in
      DNA. The aim of this modification is regulation of gene expression characteristic
      for the given organism. DNMT1 maintains methylation pattern by copying it from
      maternal to daughter stand. S-adenosylo-L-methionina is a donor of methyl group
      in his process. Disturbance in methylation level results in changes in cell
      differentiation and finally to tumor transformation. Hypermethylation of promotor
      or first exon of tumor suppression gene results in silencing of its
      transcription. While hypomethylation of regulatory sequence of protooncogene and
      retrotransposon make them transcriptionally active. DNMT1 as a key enzyme in
      maintaing of proper methylation pattern is a attractive target in anti-tumor
      therapy.

PMID- 21735818
TI  - [Genes responsible for etiopathogenesis in esophageal squamous cell carcinoma].
AB  - Esophageal squamous cell carcinoma is a very important cancer type, not only
      because of its frequent cases around the world but also because of its high
      mortality rate. Despite of the fact that this is a very rare cancer in Poland
      (around 2% of patients), we need to know more about this disease in order to find
      better ways to fight it. Epidemiological factors: smoking and use of psychoactive
      substances like alcohol and drugs, poor diet as well as changes in expression of
      genes may have influence on this cancer. During last years there has been a lot
      of researche on the role of GEAC1, which seems to play a very important role in
      normal and cancer cells. Perhaps the protein coded by this gene is an important
      part in cancer development, also being an important element in processes in
      normal tissues.

PMID- 21735819
TI  - [UDP-glucuronyltransferases, proteins of endoplasmic reticulum--structure and
      mechanism of action].
AB  - UDP-glucuronyltranferase isoenzymes, UGTs, are responsible in mammals for
      conjugation of glucuronic acid generated by UDPGA with aglicon. UDPGA is bound to
      the appropriate group of I phase metabolite or, occasionally, to the native
      compound. As a result, the aglicon polarity increases, excreatable product in
      human urine is formed and, in turn, toxic effects are reduced. UGT protein
      structure consists of 2 domens. N-terminal catalyses of aglicon binding, whereas,
      C-terminal controls the addition of uridine-5'-diphosphoglucuronic acid. UGTs are
      anchored in endoplasmic reticulum, ER, by transmembrane fragment of C-terminal
      domain. The membrane location results in the latency of enzyme activity and
      demands specific transporters for cofactor as well as for conjugation products.
      There are NST and AT(ER), respectively. UDP-glucuronyltransferases exist usually
      as homo- and heterodimers, some of them are tetramers. 19 human UGT proteins are
      described by 3 gene subfamilies, UGT1A, UGT2A and UGT2B, which are expressed
      preferentially in the liver, but also in stomach, lung and intestine epithelium.

PMID- 21735820
TI  - [UDP-glucuronyltransferases in detoxification and activation metabolism of
      endogenous compounds and xenobiotics].
AB  - Glucuronidation is a crucial pathway of metabolism and excretion of endogenous
      compounds and xenobiotics. UDP-glucuronyltransferases, UGT, catalyse
      transformations of bilirubine, steroids and thyroid hormones, bile acids as well
      as exogenous compounds, including drugs, carcinogens, environmental pollutants
      and nutrient components. From therapeutic point of view, the participation of
      UGTs in drug metabolism is of particular significance. Polymorphism of UGT1A and
      UGT2B genes resulted in various susceptibility of substrates to conjugation with
      glucuronic acid. Deactivation of xenobiotics and the following excretion of
      hydrophilic conjugates is a common task of glucuronidation, which should lead to
      detoxification. However, a lot of glucuronides were known, which expressed the
      comparable or even higher reactivity than that of the native compound. There are,
      among others, acyl glucuronides of carboxylic acids, morphine 6-O-glucuronide or
      retinoid glucuronides. They are able to bind cellular macromolecules with low or
      high strength and, as a consequence, their toxicity is saved or even increased,
      respectively.

PMID- 21735821
TI  - [Myosin VI: the unique motor protein of the actin cytoskeleton].
AB  - Myosins are actin-based motor proteins that use energy derived from ATP
      hydrolysis to generate force and move along actin filaments. Myosin VI is a
      unique motor protein because it moves towards the "minus" end of actin filament,
      which is the opposite direction to all of the other myosins studied so far, and
      therefore is thought to have unique properties and cellular functions.
      Localization and functional studies indicate that myosin VI plays a role in a
      variety of different intracellular processes, such as endocytosis and secretion
      as well as cell division, differentiation, and cell migration. These various
      functions of myosin VI are mediated by interaction with a range of different
      binding partners. In this review, we describe the structure, kinetic properties
      and functions proposed for myosin VI, and present current hypotheses on the
      mechanisms of functioning of this unique protein in vivo.

PMID- 21735822
TI  - [Molecular and cellular mechanisms of curcumin action--beneficial effect on
      organism].
AB  - Curcumin is a natural compound derived from rhizome of Curcuma longa. It is an
      active compound of turmeric used from millennia in traditional medicine. At
      present there is a very rich scientific documentation describing curcumin as an
      anticancer, antioxidative and antiinflammatory compound. Research on animal
      models revealed its not only anticancer activity but also potency as a drug
      against many other diseases of low grade inflammatory origin. Curcumin also
      counteracts many induced organ injuries. On the cellular level curcumin inhibits
      proliferation and induces apoptosis, however it is less cytotoxic for cancer than
      normal cells. There are many molecular targets of curcumin but stress signaling
      pathways and inhibition of NF- kappaB transcription factor seems to be the most
      common. Despite its low bioactivity curcumin can exert beneficial influence on
      organism, thus confirming its hormetic propensity.

PMID- 21735823
TI  - [Plant P-type ATPases].
AB  - P-type ATPases are a superfamily of membrane proteins involved in many
      physiological processes that are fundamental for all living organisms. Using ATP,
      they can transport a variety of ions and other substances across all types of
      cell membranes against a concentration electrochemical gradient. P-type ATPases
      form a phosphorylated intermediate and are sensitive to vanadate. Based on
      evolutionary relations and sequence homology, P-type ATPases are divided into
      five major families. All P-type ATPases share a simple structure and mechanism,
      but also possess domains characteristic for each family, which are crucial for
      substrate specificity. These proteins usually have a single subunit with eight to
      twelve transmembrane segments, a large central cytoplasmic domain with the
      conservative ATP binding site along with N and C termini exposed to the
      cytoplasm. Because of variety of proteins that belong to P-type ATPase
      superfamily, in this review the comparison of functional and structure properties
      of plant cells P-type ATPases is presented, as well as their important role in
      adaptation to environmental stress.

PMID- 21735824
TI  - [Functions of plant apyrases].
AB  - This publication presents results of the recent studies on plant NTPDases
      (apyrases). The structure and major physicochemical properties of this enzymes
      are reviewed. The attention has been paid to metabolic functions of apyrases from
      Solanum tuberosum and Arabidopsis thaliana. Apyrases constitute a family of
      proteins hydrolyzing phosphoanhydride bonds of nucleoside tri- and di-phosphates.
      They share common features like a similar structure, broad nucleotide substrate
      specificity and divalent cation requirement for their catalytic activity. The
      presence of plant NTPDases was detected in various cellular compartments. They
      are soluble or membrane-bound proteins. In hydrolytic processes catalyzed by
      activity of apoplastic apyrases and other ectoenzymes, adenine, ribose and
      orthophosphate are produced. These compounds are transported to the cell.
      Apyrases have been speculated to be involved in the regulation of starch
      synthesis and signal transmission. Their activity is necessary for development
      and growth of tubers and roots. Enzymes from leguminous plants activate the
      symbiosis with root nodule bacteria. Considering the fact, that NTPDases change
      the nucleotide concentration in cells and tissues, most of described functions
      may be related to the regulation of the energy charge of cell.

PMID- 21735825
TI  - [ATP-dependent FtsH and Lon chloroplast proteases].
AB  - Arabidopsis thaliana proteome contains 667 proteases; some tens of them are
      chloroplast-targeted proteins, encoded by genes orthologous to the ones coding
      for bacterial proteolytic enzymes. It is thought that chloroplast proteases are
      involved in chloroplasts' proteins turnover and quality control (maturation of
      nucleus-encoded proteins and removal of nonfunctional ones). Some ATP-dependent
      chloroplast proteases belonging to FtsH family (especially FtsH2 and FtsH5) are
      considered to be involved in numerous aspects of chloroplast and whole plant
      maintenance under non-stressing as well as stressing conditions. This notion is
      supported by severe phenotype appearance of mutants deficient in these proteases.
      In contrast to seemingly high physiological importance of chloroplast members of
      FtsH protease family, only a few individual proteins have been identified so far
      as their physiological targets (i.e. Lhcb1, Lhcb3, PsbA and Rieske protein). Our
      knowledge regarding structure and molecular mechanisms of these enzymes' action
      is limited when compared with what is known about FtsHs of bacterial origin.
      Equally limited is the knowledge about ATP-dependent Lon4 protease being the
      single known chloroplast-targeted ortholog of Lon protease of Escherichia coli.

PMID- 21735826
TI  - [Chloroplast Deg proteases].
AB  - For some chloroplast proteases ATP binding and hydrolysis is not necessary for
      their catalytic activity, most probably because even strongly unfolded substrates
      may penetrate their catalytic chamber. Deg1, 2, 5 and 8 are the best known of
      Arabidopsis thaliana ATP- independent chloroplast proteases, encoded by
      orthologues of genes coding for DegP, DegQ and DegS proteases of Escherichia
      coli. Current awareness in the area of structure and functions of chloroplast
      Degs is much more limited vs the one about their bacterial counterparts. Deg5 and
      Deg8 form a catalytic heterododecamer which is loosely attached to luminal side
      of thylakoid membrane. The complex catalyses--supported by Deg1 and one of FtsH
      proteases--the degradation of PsbA damaged due to plant exposition to elevated
      irradiance and thus these protease are of key importance for the plants'
      sensitivity to photoinhibition. Deg2 role in the disposal of damaged PsbA has not
      been elucidated. Recombinant Deg1 may degrade PsbO and plastocyanin in vitro but
      it is not clear whether this reaction is performed in vivo as well.

PMID- 21735827
TI  - [Extracellular hydrolytic enzymes produced by entomopathogenic fungi--role in an
      infection process].
AB  - Entomopathogenic fungi have a great potential in biological control of insect
      pest population. Fungal pathogens are promising source of insecticides and
      notable alterative to chemical pesticides. These fungi possess a unique mechanism
      of insects paralysis. As natural enemies of insects they attack direct host
      cuticle via a combination of mechanical pressure and cuticle-degrading enzymes.
      Entomopathogenic fungi produce several proteo-, chitino- and lipolytic enzymes,
      which are accepted as key factors in insect mycosis. The role of extracellular
      enzymes in pathogenesis is still not well understood. Profound understanding the
      mechanisms of insect paralysis by entomopathogenic fungi will help in the
      production of safer for environment and more efficiency mycoinsecticides.

PMID- 21735828
TI  - Cost analysis of adjustments of the epidemiological surveillance system to mass
      gatherings.
AB  - The article deals with the problem of economical analysis of public health
      activities at mass gatherings. After presentation of elementary review of basic
      economical approaches to cost analysis author tries to analyze applicability of
      those methods to planning of mass gatherings. Difficulties in comparability of
      different events and lack of the outcome data at the stage of planning make most
      of the economic approaches unsuitable to application at the planning stage. Even
      applicability of cost minimization analysis may be limited to comparison of
      predicted costs of preconceived standards of epidemiological surveillance. Cost
      effectiveness performed ex post after the event when both costs and obtained
      effects are known, may bring more information for future selection of most
      effective procedures.

PMID- 21735829
TI  - [Hepatitis E as zoonosis].
AB  - The hepatitis E virus (HEV) the causative agent of hepatitis E, is a non
      enveloped RNA virus. HEV is transmitted through oral consumption of contaminated
      food and water According to the currently knowledge now be considered as
      zoonosis. The main reservoir of HEV are pigs, boars and deer. For the first time
      HEV was isolated from animals (pigs) in 1997 in the U.S. Genetic analysis of
      strains isolated from pigs showed high similarity to strains HEV isolated from
      humans. This was the first evidence showing that HEV is a zoonosis. Further
      studies have shown that occupational groups e.g. veterinarians, swine breeders
      with close contact to pigs have an increased risk for HEV infections. The
      additional evidence supported the zoonotic potential of HEV were reports of acute
      hepatitis E after the consumption of undercooked meat from deer and wild boar.
      Infection of HEV in the domestic pig and wild boar population in Europe is
      widespread.

PMID- 21735830
TI  - [Studies on HCV infection prevalence in Poland--where are we?].
AB  - Numerous studies conducted in HCV infection over the past several years in Poland
      have focused on clinical course, treatment and epidemiology in selected high risk
      groups. Studies estimating the prevalence of HCV in the current general
      population are lacking. Various studies conducted in subpopulations yielding
      values ranging from 0.9% to over 4%. In the present paper we attempt to explain
      these discrepancies and assess the reliability of available data. We included
      prevalence studies published in 2000-2009, which could refer to the general adult
      population in Poland. All available studies in terms of possible conclusion about
      the general population suffered from systematic errors, most commonly selection
      bias (e.g., volunteer bias, hospital bias), or misclassification (no confirmation
      of detected anti-HCV). Given estimates often referred only to selected regions or
      age groups. Extrapolating these results to estimate the burden of illness in
      general population may lead to incorrect assessment, thus currently there is no
      scientific basis for planning screening programs and national strategies against
      HCV.

PMID- 21735831
TI  - [Therapy of hepatitis C: individualized approach to treatment].
AB  - About 70% of HCV infection fail to resolve spontaneously and progress to chronic
      hepatitis C, eventually to cirrhosis and HCC. Many studies have demonstrated that
      clinical manifestation and the outcome of HCV infection are negatively influenced
      by a variety of cofactors and comorbidities. Moreover many of these cofactors
      often reduce the chance of achieving a sustained virological response (SVR) with
      only available combination therapy with pegylated interferon-alpha2 (PEG-IFN) and
      ribavirine (RBV). Dose modification of both currently licensed drugs for
      treatment of HCV infection and variations of treatment duration are the most
      discussed strategies to optimized the therapy, particulary in patients infected
      by genotype 1 HCV. Tailoring the duration of peginterferon/ribavirine therapy to
      HCV kinetics is useful to optimize the results of therapy.

PMID- 21735832
TI  - [Role of simple noninvasive markers of liver fibrosis in qualification to
      treatment in patients with chronic hepatitis C].
AB  - Assessment of liver fibrosis in patients with chronic hepatitis C (CHC) is
      essential for determination of prognosis, monitoring of the disease and guiding
      therapeutic decisions. Current gold standard for diagnosis of hepatic fibrosis is
      liver biopsy. Since it has several limitations and risks there is ongoing
      development of alternative means to assess fibrosis. In recent years intensive
      research in the field of noninvasive assessment of liver fibrosis allowed to
      establish few laboratory markers, that answer some questions about severity of
      the disease. Among these methods there are direct indices using parameters
      reflecting processes of fibrogenesis and fibrolysis as well as indirect indices
      using widely available laboratory parameters. This review presents 9 different
      simple markers with an overview of their statistical performance in determining
      liver fibrosis and their potential role in management of patients with CHC.
      Despite conducting many validating studies many questions remain about their
      indications, accuracy and a need of validation before they are put into
      widespread use. Further evaluation of noninvasive methods of liver fibrosis
      prediction is a priority in clinical hepatology research.

PMID- 21735833
TI  - [Attempts to treat chronic hepatitis C with HCV protease inhibitor].
AB  - The standard of treatment of chronic hepatitis C is pegylated interferon and
      ribavirin. The improvement of sustained viral response rates is sufficient with
      new HCV specific inhibitors against the NS3/4A protease and the NS5B polymerase.
      First generation protease inhibitors will offer higher SVR for both naive (70
      80%) and treatment-experienced (40-50%) patients infected with HCV when added to
      standard pegylated interferon and ribavirin. Because of the high genetic
      heterogeneity of HCV and its rapid replication, monotherapy with directly acting
      antivirals agents poses a high risk for selection of resistance variants. Year
      2011 should bring the approval of the first generation of protease inhibitors
      that will offer higher cure rates for genotype 1 HCV patients and open the door
      for eventual testing of interferon-free regiments.

PMID- 21735834
TI  - Etiology of measles suspect cases reported in 2006-2007 in Poland.
AB  - To achieve measles elimination, an efficient surveillance system for rash
      illnesses is necessary. The aim of the present study was to ascertain which
      viruses, other than measles, are causing measles-like illnesses (MLIs) in Poland.
      Serum samples (n=278) collected from MLI cases and submitted to the National
      Reference Laboratory during 2006-2007 were investigated for anti-measles (MeV),
      rubella (RUBV), parvovirus B19 (B19V), Epstein-Barr (EBV) and herpesvirus type-6
      (HHV-6) IgM presence. Age was strongly associated with MLIs etiology. In the
      youngest age group, 0-4 years, MeV and HHV-6 infection were prevailing, while in
      group of 5-9 years--RUBV and B 19V. Measles was confirmed more often in patients
      with high fever (p < 0.001) and with rash lasting longer than 5 days (p < 0.001).
      The type of rash was not significantly associated with MeV infection. Our results
      strongly suggest that according to WHO EURO strategic plan, Poland is close to
      elimination phase. High number of MLIs were caused by pathogens other than
      measles. Addition of anti-B 19V IgM testing to routine MLIs screening protocol
      may improve system performance in the more advanced stages of measles
      elimination.

PMID- 21735835
TI  - [Immunization of adolescents and adults as the strategy of improvement of
      epidemiology of pertussis].
AB  - Increase of pertussis incidence has been recognised mainly among adolescents and
      adults since 90. As adolescents and adults sustain the reservoir of infection for
      non immunized and not completely immunized newborns and neonates, increased rates
      of pertussis are dangerous. The improvement of pertussis epidemiology might have
      been obtained through routine immunization of adolescents and adults able to
      interrupt of B. pertussis circulation in the population. The improvement of
      surveillance and diagnostics might have result in better detection of the disease
      in children at the age up to first year and in older age groups.

PMID- 21735836
TI  - [Indirect, population effect of mass pneumococcal vaccinations (PCV7) on all
      cause pneumonia incidence in Kielce, Poland].
AB  - In these article they made analysis of indirect, population effects of mass, free
      of charge, pneumococcal vaccinations (PCV7) on all-cause pneumonia incidence in
      Kielce, Poland. The strongest and significant fall (p=0.00079) in all-cause
      pneumonia incidence in the analyzed period 2005-2009 compared with remaining
      groups were observed in the group of children under 2 of years of life. He
      amounted to the 74% (around 25/1000 in 2005; 6/1000 in 2009). In the entire
      ancient group 0-29, embracing children under 2 yrs of life the fall of pneumonia
      incidence rate amounted to the 48% (from 2.8/1000 in 2005; 1.5/1000 in 2009). In
      the age 65+ group the fall in the incidence amounted to the 45% (19/1000 in 2005;
      <11/1000 in 2009 r.). At the moment they didn't observe, of such a fall in age
      groups 30-49 yrs and 50-64 yrs. Presented results are pointing population
      effectiveness of applied in Kielce mass vaccination in a 2+1 scheme. Analyzing
      only pneumonia requiring the hospitalization they tried at work to estimate, in
      the definitely simplified way, financial effects of mass pneumococcal vaccination
      in Kielce. Analysis showed at children up to 2 yrs frugalities of the row of the
      174,420 zloty annually. In the group above 1 year of life analogous analysis
      showed frugalities of row 789,480 zloty. Results presented by us should, in our
      opinion, to induce decision-makers for free of charge mass pneumococcal
      vaccinations to entire Poland.

PMID- 21735837
TI  - [Listeria monocytogenes in human infections].
AB  - The Listeria genus is distinguished into six species from which just one-
      Listeria monocytogenes is pathogenic for humans. The main route of acquisition of
      Listeria is through the ingestion of contaminated food products. An important
      element of the L. monocytogenes pathogenesis infection is affiliation with high
      risk group of immunocompromised patients, infants or pregnant women, who infected
      by this microorganism can lead to miscarriage. Listeriosis can appear in the form
      of sepsis, infection of the nervous system or local abscesses. Another form of
      listeriosis is gastrointestinal tract infection--noticed in case of food
      poisoning outbreak.

PMID- 21735838
TI  - [Listeriosis of the central nervous system: epidemiological and diagnostic
      aspects--own observations].
AB  - The aim of the study was to evaluate clinical and laboratory findings and
      predisposing factors for Listeria monocytogenes (Lm) meningitis. METHODS: 17
      intensive care unit patients (12 M, 5 F), aged 54.4 +/- 15.3 yrs, were studied.
      CNS listeriosis was confirmed by culture of cerebrospinal fluid (CSF) or CSF
      pleocytosis coupled with Lm bacteriemia. RESULTS: The frequency of central
      nervous system (CNS) listeriosis among patients with bacterial meningitis was
      5.5%. Meningeal signs were present in all patients. 15 patients had impaired
      level of consciousness. Possible predisposing factors occurred in 15 patients.
      The average CSF white blood cell count was 1034 +/- 1064 cells/microl.
      CONCLUSION: Symptoms and signs of patients with CNS listeriosis were not
      different from those usually found in other bacterial meningitis. A trend toward
      fewer WBC in CSF was revealed. Most patients with Lm meningitis were
      immunocompromised.

PMID- 21735839
TI  - [Epizootic situation of rabies in domestic animals in the city of Wroclaw 2000
      2009].
AB  - Rabies is a viral contagious disease. During the disease there are unreversable
      inflammatory changes of the brain ending with death. Thus, every human and animal
      bite case is epidemiologicaly analyzed. The aim of the study was an analyze of
      cases of observation of companion and wild animals that had bitten humans in the
      city of Wroclaw and surrounding in the years 200-2009. In that time 925 cases
      were reported and observed. Among these group dogs were 81%, cat's 13,5% and
      other species 5,5%. In 925 observations cases 928 people were hurt, but only
      10,1% contacted the doctor of human medicine.

PMID- 21735840
TI  - [The analysis of the occurence of human papillomavirus genotypes in patients
      surveyed in NIPH-NIH in 2007-2009].
AB  - The aim of this study was to determine the frequency of each genotype of
      papillomavirus caused infection in human. In the years 2007-2009 in NIPH-NIH
      diagnostic tests were carried out, among 250 participants (222 women and 25 men).
      The samples were tested by PCR and subsequently LiPA hybridization was performed.
      Positive results were obtained in 66.4% and negative in 27.2% of all examined
      cases. In 30.0% of the examined cases only one genotype was detected. Mixed
      infections were diagnosed in 32.0% (of cases from one person). In mixed
      infections two (15.6% of tested patients), three (11.6%), four (4.4%) and even
      five genotypes were detected. HPV 51 was the most frequently detected type (in
      over 20% of cases), followed by HPV 66 (in 14%) and HPV 11 (over 11%). The
      genotypes 43 and 80 were not detected. HPV 17 and HPV18 types were confirmed in
      7.6% and 4.8% of all tested cases.

PMID- 21735841
TI  - [Cervical cancer in Poland and in the world--in the light of incidence and
      mortality data].
AB  - Cancer of the cervix uteri is a substantial problem of public health in Poland
      and some countries in the world. It develops within precancerous lesions of the
      cervix caused by oncogenic human papillomavirus (HPV) types. Epidemiology of
      precancerous cervical lesions and cervical cancer in Poland, Europe and selected
      countries in the world as well as 5-year survival rate of women diagnosed with
      cervical cancer is discussed.

PMID- 21735842
TI  - [Risk factors of cervical cancer and possibilities of primary prevention].
AB  - Cancer of the cervix uteri is one of the few malignancies with identified
      necessary etiological factor and described steps of its development. Sexually
      transmitted human papillomavirus (HPV) infections are the etiological factor of
      cervical cancer. Despite the fact that HPV infections are one of the most
      frequent in female reproductive tract, they rarely cause premalignant conditions
      which, if untreated, may lead to development of cervical cancer. Attempts of
      primary prevention of cervical cancer through reduction of HPV infections by
      propagation of proper sexual behaviour and use of condoms have limited efficacy.
      At present the most effective form of cervical cancer primary prevention are
      prophylactic vaccines against two most common HPV types: 16 and 18, which are
      responsible for approximately 70% of all cervical cancer cases in the world.

PMID- 21735843
TI  - [The impact of UV radiation B and C in vitro on different of bacteria strains
      isolated from patients hospitalized in the Warsaw Medical University Clinics].
AB  - INTRODUCTION: Infections in human body caused by various microbes are a
      significant problem in modern medicine. Special attention is put to infections of
      wounds, which are a significant threat to the life of patients. Attempts to treat
      these wounds base mainly on the application of various chemical preparations
      (locally) and systematic antibiotic treatment. UV radiation, because of its anti
      bacterial activity, appear a complementary issue in therapy. AIM OF THE SURVEY:
      The aim of this study was an examination of the sensitivity of bacteria strains
      isolated from patients hospitalised in the Warsaw Medical University clinics, and
      prove that antibiotics and operation of UV B and C radiation with Endolamp 474
      may become a complementary or alternative method of treatment. MATERIAL AND
      METHODOLOGY: The study used 65 strains grown aerobically (15 strains of
      Escherichia coli, 20 strains of Pseudomonas aeruginosa, 15 strains of
      Staphylococcus aureus, 15 strains of Streptococcus and Enterococcus sp). The same
      strains were planted on different excipients and were subjected to UV radiation
      using Endolamp 474. Correctly prepared strains were radiated from a 25 cm
      distance in various durations (from 5 seconds to 105 seconds). RESULTS AND
      CONCLUSIONS: As a result of UV irradiation of microorganisms studied B and C
      using 474 Endolampy received varied, but the great sensitivity to the effects of
      this radiation, in all tested bacterial strains. UV radiation on microorganisms
      requires further study, also in vivo.

PMID- 21735844
TI  - [Mosquito control on selected area in Poland after the flood in 2010].
AB  - After the flood in 2010 in many regions of Poland mosquitoes occurred in huge
      number and chemical control of them was performed. In Legionowo district the
      aerial application of deltamethrin-containing product was done. In the study the
      efficacy of the treatments was described. Mosquitoes were caught in CDC traps in
      five places located in the treated area before treatments, after the 1st and
      after the 2nd treatments chemical. The chemical control resulted in mean
      reduction of 53.8% in mosquito numbers after the 2nd treatment (48.1%-57.2%).
      Efficiency results were much lower than those obtained in control programs
      realized with the use of microbial control agent. Results obtained indicate, that
      the integrated mosquito control program should be elaborated for this area,
      enabling the use of biological and chemical control methods to obtain better
      efficiency and protection of the environment.

PMID- 21735845
TI  - [The parents opinion on the risk factors of autism in their children].
AB  - The mothers' opinions about the reasons of their children autism have been
      collected during case-control study on risk factors of that disease. The
      relationship between different opinions and mothers' characteristics have been
      analyzed. The categories of autism reasons mentioned by mothers have been related
      to the current knowledge about the risk factors of disease.

PMID- 21735846
TI  - [E-health--challenge for health care system].
AB  - E-health and systems related to the electronic patient record (EPR) are seen as
      important factors in the development of the health care System. In 2004 European
      Commission had adopted e-Health Action Plan, which indicated the development
      directions of European e-Health. In Poland, the main development trends and
      Government course of actions in this regard, are contained in the document
      Computerization plan "e-Health Poland" 2009-2015. The European Commission defines
      e-Health as an application of tools and services, information and communication
      technologies in healthcare. EPR is a collection of patient data that are stored
      in a certain place and it is possible to access them. E-health and EPR are
      closely related to the concept of interoperability. Denmark is one of the
      countries in which the information services and information technology in
      healthcare is mostly used. The introduction of ERP involves a lot of positive
      effects. Using the ERP, stored data can be optimally used by both physicians and
      patients. However, also risks associated with data security need to be
      considered. Furthermore, the Polish law defines in great detail the issues
      associated with creating, storing and sharing medical records (1). According to
      the Act from 17 February 2005, concerning the computerization of public service
      activities, it possible to keep medical documentation in electronically form.

PMID- 21735847
TI  - [Generalized self-efficacy in relation to anti-health behaviours of general
      practitioners exemplified by smoking].
AB  - The purpose of the present work is to make an assessment of generalized self
      efficacy of general practitioners and to investigate its relationship with socio
      demographic factors and undertaking risky behaviours taking smoking as an
      example. The participants of the research encompassed 500 general practitioners
      aged 27-75 living in Poland. The participants' level of generalized self-efficacy
      was measured first, then, the relationship between generalized self-efficacy,
      socio-demographic variables and GP's attitudes towards smoking was investigated.
      The averaged level of GP's generalized self-efficacy was 29.425 +/- 3.64, which
      is within high referential values. There have been statistically significant
      relationships between self-efficacy and sex of the participants (men achieved
      higher scores than women). There have been no significant differences found in
      the perception of self-efficacy in terms of age and marital status. Statistically
      significant relationships between generalized self-efficacy and smoking were
      found only with general practitioners addicted to smoking and smoking every day
      (in this group, the GSES score was 29.34; SD = 3.60, while in the non-smokers'
      group the score is significantly higher and is 31.19; SD 4.23). When implementing
      protective actions related to smoking special attention needs to be devoted to
      the psychological resources stimulating pro-health activity, including
      generalized self-efficacy.

PMID- 21735848
TI  - [Validation of the questionnaire for adolescents concerning ailments of
      lumbosacral region. Part I: reliability of questions about presence and character
      of pain].
AB  - The first part of the series of articles is dedicated to the process and the
      results of reliability testing of the questionnaire designed for pupils aged 13
      18, the tested questions concerning ailments of the lumbosacral region (LBP) and
      their characteristics. 124 persons aged 13-17 took part in the research. The
      "test-retest" method was used, the questionannaires being filled in twice by
      every pupil in no more than 7-day period. Questions were asked about LBP, the
      accompanying ailments, the intensity of pain, the length of the episode, the
      cause of the beginning, the constant pain, the activities that worsen or reduce
      symptoms, the necessity of therapy, the presence of functional disorders
      connected with LBP, height, weight and basic ,,red flags" which could indicate
      pain of specific origin. Results that were obtained in the process of testing
      indicated that reasoning was invalid when based on questions about the length of
      episode (60% repeatable, rank correlation 0.3) and on questions about activities
      that worsen or reduce pain (respectively 34 i 35% repeatable answers). The rest
      of questions were found acceptably reliable.

PMID- 21735849
TI  - [Validation of the questionnaire for adolescents concerning ailments of
      lumbosacral region. Part II: reliability of questions about risk factors].
AB  - The second part of the series of articles presents the reliability testing
      results of questions concerning factors that could influence or originate the
      symptoms of low back pain (LBP). The questions are a part of the questionnaire
      designed for pupils aged 13-18. 124 persons aged 13-17 were tested. The
      questionannaires were filled in twice by every pupil in no more than 7-day
      period, and then the answers were compared according to the test-retest method.
      The questions concerning risk factors were about: the intensive growth period,
      chronic diseases, the medical diagnosis of LBP, concomitant faulty posture, sport
      training and leisure time physical activities, leisure time spent sitting,
      possible nutritional deficiencies, the amount of sleep, the impact of lifting and
      dislike for school. Results that were obtained in the process of testing
      indicated that reasoning would be invalid if based on questions about sports (45%
      repeatable answers), about leisure time physical activities (Polish version of
      the leisure time exercise questionnaire of Godin and Shepard--correlation for the
      Godin and Shepard index was 0,29) and about intensive growth period (small number
      of valid responses indicates that the question is incomprehensible for
      adolescents). The rest of questions were found acceptably reliable.

PMID- 21735850
TI  - [Validation of the questionnaire for adolescents concerning ailments of
      lumbosacral region. Part III: validity].
AB  - The third part of the series of articles includes the results of validity and
      coherence check conducted over the LBP questionnaire designed for pupils aged 13
      18. 22 adolescents aged 13-17 were randomly chosen from the group of 124 pupils,
      who filled in the questionnaire using stratification to 3 groups: without LBP,
      LBP in a life time, but not in the week preceding the testing and LBP in the
      preceding week. The validity of questions was tested by comparison to the data
      obtained from parents and in clinical testing conducted by a physiotherapist,
      which took place within two weeks from the first questionnaire session. The
      questions were found valid if the answers or indexes counted from the answers
      were consistent with data from clinical testing and from parents. For birth date,
      height and weight data from parents were used. Data from clinical testing served
      to verify: height, weight, presence and location of pain (local symptoms of
      overloading were palpated), faulty posture and directional preference according
      to McKenzie. With reference to some questions the coherence check was performed,
      by comparing the answers to questions logically linked. As a result of validity
      and coherence check rejected were the questions about: intensive growth period
      (small number of answers together with many incoherent ones), about beginning of
      pain episode (lack of coherence), about directional preference (differences with
      clinical testing) and about faulty posture (not consistent with findings in
      clinical testing). On the other hand the question about presence of LBP proved to
      be highly specific, good results were also found as to the questions about birth
      date, height and weight. The rest of the questions tested were found acceptable.

PMID- 21735851
TI  - [Reporting of tuberculosis in Lodz voivodeship--procedures of the state sanitary
      inspection].
AB  - The purpose of this article is to draw readers' attention to irregularities that
      appear at the organized supervision within the scope of health service aimed at
      fight with tuberculosis in Poland. The tuberculosis registration system and its
      analysis has been functioning in the country for several years and it has been
      conducted by entities specialized in tuberculosis cases in the cities,
      voivodeships and the country. In 2009 The State Sanitary Inspection in Lodz
      voivodeship took over the supervision of overall tuberculosis cases register and
      introduced its uniform prevention and action procedures against tuberculosis in
      the region. The aim is to restrict to minimum the negligence such as: not
      reporting the tuberculosis cases, lack of sent applications registers, lack of
      actions according to people who were contacts of TB cases.

PMID- 21735852
TI  - [Cost of lost productivity in pharmacoeconomics analysis. Part I. A systematic
      review of the literature].
AB  - The inclusion of indirect costs of illness in economic studies is still a subject
      of considerable debate. The aim of the systematic literature review was to
      present the Polish economic practice concerning indirect costs evaluation of
      healthcare interventions. MEDLINE, EMBASE, Cochrane Library and Polish Medical
      Bibliography (PBL) were searched. Cut-off dates were set to February and March
      2009. The main specific keywords were 'indirect costs' or 'costs and cost
      analysis'. Nineteen studies fulfilled the inclusion criteria for this review, of
      a total of 2300 references. Seventeen out of 19 studies were cost of illness
      studies, 2 were economic analyses. Methods of indirect costs evaluation were all
      based on human capital approach. The work absenteeism unit time measure used to
      value productivity loss were average salary (9/19), Gross Domestic Product (GDP)
      per capita (7/19), Gross National Product per capita (1/19), GDP per active
      worker (1/19), sold production of industry per active worker (1/19). Mean
      indirect costs were ca. 58% of total costs (range: 16%-98%). In 5 studies
      transfer payments were added to productivity loss category. Indirect cost is
      rarely included in the economic analyses in Poland. Various methods of indirect
      costs calculation limit comparison between studies and support the need for
      development of robust and widely accepted methodology.

PMID- 21735853
TI  - [Cost of lost productivity in pharmacoeconomics analysis. Part II. Survey in the
      expert group].
AB  - The aim of the survey was to collect data on practice and preferences of decision
      makers and experts in health economics concerning the role of indirect costs in
      Poland. The questionnaire contained 18 questions covering the need for indirect
      costs calculation in economic evaluations and measures used to calculate indirect
      cost. Fifty four respondents related to health economics returned completed
      questionnaires. Mean age of respondents was 33,3 years; mean experience in health
      economics 4.7 years; 43% (23/54) of responders had non-economic background; 30%
      each were users and doers of health technology assessment reports. All (excluding
      one) responders indicated that indirect costs should be calculated in
      pharmacoeconomic studies. Twenty three (i.e., 43%) responders indicated human
      capital approach as the best method to estimate costs from societal perspective;
      friction cost method came second best 11%; 42% respondents had no opinion. The
      doers of economics evaluations pointed to GDP per capita (61%, 11/18), average
      salary (61%, 11/18), and costs of sick pay or injury benefit (61%, 11/18) as
      measures which could be used to value production losses. Indirect costs are
      considered important component of economic evaluations of healthcare
      interventions in Poland. The lack of widely accepted methods for indirect cost
      evaluation support further research.

PMID- 21735854
TI  - [Cooperation in health behaviour change programmes. An example of nutrition in
      adolescents].
AB  - Article presents issue of cooperation in realization of health behaviour change
      programmes. An example of eating in adolescents is used as an illustration. Tasks
      and actions of all contributors are outlined, as well as topic of cooperation
      among them. Motivation to cooperate and potential problems in cooperation are
      analyzed.

PMID- 21735855
TI  - [An outbreak of tuberculosis in which environmental factors influenced
      tuberculosis infection].
AB  - OBJECTIVE: We encountered a contact group investigation in which differences in
      environmental factors, including the ventilation frequency and the airflow, led
      to differences in the infection risk. MATERIALS AND METHODS: The index case was
      diagnosed with tuberculosis after cough and sputum persisted for 9 months. The
      patient was an instructor working at vocational schools A and B. Sixty-six
      instructors/staff and 446 students had contact with this patient at the schools.
      The patient taught 24 regular courses and 21 short-term courses at the 2 schools
      after symptom onset through to the final day of work. RESULTS: In a contact
      investigation of instructors/staff, one person with latent tuberculosis infection
      (LTBI) was identified. Subsequently, 30 and 240 students with the closest
      contacts and those with 8-hour or longer contact with the index case,
      respectively, were examined. In School A, of the 162 students examined, one
      student developed tuberculosis, 7 were QFT-positive, one was QFT-doubtful, 147
      were QFT-negative or judged as not infected (either QFT-negative, or a tuberculin
      skin test of erythema less than 20 mm, including past history of LTBI treatment
      or TB treatment), and 6 were not examined. In School B, of the 108 students
      examined, no one developed tuberculosis nor was QFT-positive, 4 were QFT
      doubtful, 98 were either QFT-negative or judged as not infected, one was QFT
      indeterminate, and 5 were not examined. Since the onset of tuberculosis and QFT
      positivity occurred in only School A, the difference in the incidence of
      infection between the 2 schools, despite the levels of contact being similar, was
      assumed to be due to environmental factors. Thus, the ventilation frequency,
      which had been not reported initially, was reinvestigated. The frequency of air
      change was as low as 0.45-1/hour in School A, whereas it was better (3.57-7/hour)
      in School B. Moreover, the air flew from the instructor side toward students in
      School A, while it was reversed in School B. DISCUSSION: It was clarified that
      the ventilation frequency and airflow markedly influenced infection. It is
      important to investigate environmental factors on epidemiological investigations
      and to educate people regarding the importance of ventilation.

PMID- 21735856
TI  - [Epidemiological significance of patients with extra-pulmonary TB--a study of
      10,082 patients with tuberculosis].
AB  - OBJECTIVES: To elucidate the epidemiological significance of patients with extra
      pulmonary TB. SUBJECTS AND METHODS: The subjects of this retrospective study were
      10,088 TB patients registered in Aichi prefecture between 1989 and 2003. Of
      these, 8,629 patients had pulmonary TB and 1459 had extra-pulmonary TB. All
      registration files were reviewed to identify the epidemiological links of
      patients. When linked patients with an interval of less than 10 years between
      registrations were found, the earlier registered case was considered the primary
      or index case, and the other patients were regarded as secondary cases. The index
      case rate (ICR) for a category of patients was defined as follows: ICR=NI/NA,
      where NA: number of TB patients in a category A, and NI: number of index cases in
      category A. RESULTS: The ICR for the 1,459 extra-pulmonary TB patients was 1.1%,
      which was significantly different from 7.2% for 3332 patients with sputum smear
      positive pulmonary TB (p < 0.001), as well as from 2.1% for 2139 patients with
      sputum smear-negative and bacillus-positive pulmonary TB (p < 0.05). The ICR
      differences were not significant between extra-pulmonary TB patients and 3,158
      patients with bacteriologically negative pulmonary TB (1.2%). Of the 16 index
      cases with extra-pulmonary TB, the organs in which tuberculosis was found were
      the pleura in 13 patients, the bone in two, and the hilar nodes in one. The
      relationship between the 16 index cases and 18 secondary patients were husband
      wife in 7 pairs, parent-child in 7 pairs, brother or sister in 2 pairs, and
      grandparent-grandchild in 2 pairs. The interval of the dates of registration for
      the index and secondary patients was within one year in 14 pairs or 77.8%.
      DISCUSSION: The index cases with extra-pulmonary TB can be considered as a good
      control in the epidemiological study on the ability of TB transmission in
      patients with pulmonary tuberculosis, so that they can form clusters by chance,
      or false positive clusters. CONCLUSION: Our findings suggest that patients with
      extrapulmonary TB have no ability of TB transmission, nor do patients with
      bacteriologically negative pulmonary TB.

PMID- 21735857
TI  - [Retrospective cohort study of risk factors for adverse effects of
      antituberculous therapy].
AB  - PURPOSE: This study was designed to identify clinical risk factors for adverse
      effects of antituberculous therapy and their frequency. METHODS: A retrospective
      study of cohorts was undertaken from April 2004 to March 2007. We analyzed the
      clinical records of 861 patients with tuberculosis treated at Higashi Nagoya
      Hospital. The factors that were associated with adverse effects in univariate
      analysis (P < 0.1) were then subjected to multivariate Cox regression analysis
      for calculation of the hazard ratios (HRs) and their 95% confidence intervals
      (95% CIs). RESULTS: Suspension of antituberculous therapy was necessary because
      of adverse effects in 247 patients (28.7%). The chief adverse effects leading to
      discontinuation of treatment were liver dysfunction (12.9%), skin rash (6.7%),
      and gastrointestinal dysfunction (4.1%), while other effects accounted for less
      than 5.0% of discontinuations. Risk factors for liver dysfunction according to
      Cox proportional hazards analysis were HCV infection (HR 2.86; 95% CI 1.59 to
      5.15; p < 0.001); hepatocellular damage at admission (HR 2.06; 95% CI 1.25 to
      3.39; p = 0.005) and high-dose isoniazid (increase per mg/kg: HR 1.36; 95% CI
      1.18 to 1.56; p < 0.001). Collagen disease was a risk factor for skin rash (HR
      6.06; 95% CI 2.81 to 13.05; p < 0.001). Risk factors for gastrointestinal
      dysfunction were a high body mass index (increase per kg/m2: HR 0.80; 95% CI 0.71
      to 0.91; p < 0.001) and advanced age (increase per year: HR 1.03; 95% CI 1.01 to
      1.06; p 0.018). CONCLUSION: Adverse effects may lead to substantial additional
      medical costs because of the need for more medications and tests, as well as a
      longer hospital stay. Identification of the risk factors for adverse effects of
      antituberculous therapy should help to minimize such events in tuberculosis
      patients.

PMID- 21735858
TI  - [A case of pulmonary tuberculosis with diminished lung function whose paradoxical
      reaction led to death].
AB  - Paradoxical reaction in tuberculosis treatment is not generally fatal. On rare
      occasion it can lead a patient with diminished lung function and poor general
      condition to death. A 60-year-old man with history of left upper lobe resection
      from tuberculosis was referred to our hospital due to the recurrence of
      tuberculosis. Sputum examination showed a positive smear with a Gaffky score of
      10, and the chest X-ray and CT revealed pulmonary infiltrate with many cavities
      (bII2) on the whole left lung field. Anti-tuberculosis drugs (isoniazid,
      rifampicin, ethambutol and pyrazinamide) were administered, but his high fever
      persisted, and the infiltrate on the chest X-ray deteriorated. While the positive
      sputum smear persisted, the culture became negative after one month. The
      tuberculous bacilli were susceptible to all anti-tuberculosis drugs in vitro.
      Though we performed examinations and trial treatments for non-tuberculous
      conditions such as pneumonia and drug-induced pneumonia, the patient died after 6
      months. A necropsy specimen taken from the worsening lesion (the right upper
      lobe) as shown on the chest X-ray revealed many epithelioid granulomas. The
      patient had malnutrition, diabetes, alcoholic hepatic disorder, and insanity. It
      is supposed that although antituberculosis drugs were effective, a large quantity
      of killed organisms was continuously excreted from many cavities in the left lung
      toward the right lung. Lesions in the right lung thus newly produced in this
      paradoxical reaction seemed to reduce the remaining lung function. In addition,
      poorly controlled diabetes caused deteriorated heart function. These multiple
      factors contributed to the poor prognosis of the patient and his ultimate death.

PMID- 21735859
TI  - [Present status of studies on epidemiology and molecular epidemiology of
      Mycobacterium kansasii, in special reference to its epidemiology].
AB  - Mycobacterium kansasii, a slow-growing photochromogen, causes serious pulmonary
      diseases in humans. Since the 1980s the isolation rate of M. kansasii has been
      surpassed by that of Mycobacterium avium complex (MAC). Pulmonary disease caused
      by M. kansasii is known to be more common in urban areas than in rural areas, and
      its changing epidemiologic features and geographical distribution have been known
      for several decades. The disease had been found almost only in and around Tokyo
      areas until the 1970s, but after the 1990s, the disease spread to the rest of
      Japan. The incidence rate of the disease due to M. kansasii remained at the same
      level, while non-tuberculous mycobacterioses as a whole are rapidly increasing,
      especially because of the increase in Mycobacteriu avium complex diseases, and
      because of the improvement of identification techniques in recent years. This
      change in the epidemiologic picture of M. kansasii in Japan seems to be
      influenced by the international trends of this disease. The complicated
      environmental and other factors related to M. kansasii infection are discussed in
      this review.

PMID- 21735860
TI  - [Nontuberculous mycobacteriosis mortality in Japan].
AB  - The aim of this research was to clarify epidemiological characteristics of
      nontuberculous mycobacteriosis deaths in Japan. We analyzed the frequency of
      deaths due to nontuberculous mycobacteriosis (NTM) and regional differences using
      the Vital Statistics of Japan, published by the Ministry of Health, Labour and
      Welfare. The crude death rate was calculated using the Population Census of Japan
      published every 5 years (Ministry of Internal Affairs and Communications). In
      addition, changes in the proportions of death cases due to NTM disease among
      total autopsies were calculated using the Annual of the Pathological Autopsy in
      Japan (The Japanese Society of Pathology). RESULTS: NTM disease deaths appeared
      for the first time in 1970, with a marked increase by 2007, when there were 912
      certified deaths. The increase was more marked after the mid-1990s. The number of
      women's deaths exceeded 300 in 1999 and reached 570 in 2007, while that of men
      exceeded 300 in 2001 and remained at nearly the same level until 2007. The death
      rate increased in all eight regions of Japan. The highest single-year regional
      death rate was 212 in Kanto in 2005. However, correcting by population size, the
      crude death rate was higher in the western regions of Japan than in the eastern
      ones. The proportion of NTM among total autopsies also showed an increase from
      0.066% in 1993 to 0.304% in 2007. Included in the report is a comparison of
      trends of NTM deaths with those of major respiratory diseases including
      tuberculosis, emphysema, bronchial asthma and airway cancers.

PMID- 21735861
TI  - [Tuberculosis annual report 2009--series 3. Childhood TB].
AB  - The number of newly reported childhood tuberculosis (TB) cases (0-14 years old)
      in 2009 was 73, corresponding to a case rate of 0.43 per 100,000. In 2007 and
      2008, the case numbers and rates of childhood TB increased slightly from the
      previous years, but in 2009 the case number and case rate were the lowest in the
      long history of the Japanese TB surveillance system. Among 73 childhood TB
      patients, 34 (46.6%) were aged 0-4 years, 3 (4.1%) were foreigners and 27 (37.0%)
      were extra-pulmonary TB. No TB meningitis case in this age group (0-14 years old)
      was reported for 3 years (from 2006 to 2008), but one case was reported in 2009.
      Also, 4 cases of disseminated TB were reported in 2009, the highest figure during
      those 10 years (from 2000 to 2009). As for the mode of detection in 2009, 33
      patients (45.2%) were detected at medical institutions with some symptoms or
      signs, 24 patients (32.9%) were detected by family contact examination, and 8
      (11.0%) were detected by other contact examination. In the previous year (2008)
      these proportions were respectively 36.8%, 45.3% and 8.4%. Of the 47 prefectures
      in Japan, 27 had no cases of childhood TB in 2009. Childhood TB cases were
      concentrated in metropolitan areas, such as Osaka (13 cases), Tokyo (11 cases)
      and Kanagawa prefecture (7 cases).

PMID- 21735862
TI  - Make the most of your life.

PMID- 21735863
TI  - Disinterested parties hard to come by. Feeling passionate about an issue is not
      the same as possessing a conflict of interest.

PMID- 21735864
TI  - Clarity needed.

PMID- 21735865
TI  - Survey of pediatric dentists' own oral health behavior.
AB  - Oral health behavior is voluntary and, therefore, requires motivation. Dentists
      serve as role models for their patients. We sought to determine the pediatric
      dentists' own adherence to oral health behavior recommendations through a 14
      question survey administered to 129 pediatric dentists. A significant percentage
      of respondents fell short in brushing, flossing and regularity of dental exams. A
      trend was seen for decreasing exam frequency with decreasing population density
      and for increasing brushing frequency with increasing age. Although most dentists
      follow their profession's oral health guidelines, a significant percentage does
      not.

PMID- 21735866
TI  - Immediate provisional restoration of implant placed using flapless surgery and
      ridge mapping. Case report.
AB  - Loss of an anterior tooth as the result of trauma is relatively common,
      especially in the young. Orthodontic treatment is not always the definitive
      therapy of choice; instead, an implant can be placed to replace the missing
      tooth. This article describes the case of a 19-year-old woman whose maxillary
      left central incisor was replaced by an immediately restored dental implant,
      placed using flapless surgery. The implant achieved excellent primary stability,
      as determined by resonance frequency analysis, so it was immediately restored
      with a provisional acrylic resin crown in no centric occlusion. This case report
      supports the use of single implants for replacing a missing anterior tooth where
      esthetics are a priority.

PMID- 21735867
TI  - Granulocytic sarcoma of palate. Case report and review of literature.
AB  - A rare case of granulocytic sarcoma of the hand and palate, also known as
      chloroma, occurring in an adolescent patient is presented. Diagnostic clinical
      criteria, along with treatment pictures, are also reviewed.

PMID- 21735868
TI  - Panoramic radiographic demonstration of bilateral tonsilloliths.
AB  - Calcifications can develop within the crypts of the palatine tonsil. During
      routine dental panoramic radiography, these tonsillar calcifications, or
      tonsilloliths, may be visualized superimposed upon the mandibular ramus. Their
      anatomic location and radiographic appearance are such that confusion with
      parotid sialolithiasis may occur. This report defines the symptomatology and
      differential diagnosis of these tonsilloliths.

PMID- 21735869
TI  - Cytotoxicity of composite resins before and after expiration date. Preliminary
      report.
AB  - The aim of this study was to compare the cytotoxic effects of expired and non
      expired resin-based composite materials at two, five and seven days on L929
      cells. Disc-shaped test samples of expired and non-expired composite materials
      were prepared according to manufacturers' instructions. The samples were
      transferred into a culture medium for 24 hours. Eluates were obtained and
      pipetted onto L-929 mouse fibroblast cultures and incubated for evaluation after
      two, five and seven days. After each of the incubation periods, measurements were
      performed by MTT assay. The degree of cytotoxicity of each sample was determined
      according to the reference value represented by the cells with a control.
      Statistical significance was determined by two-way analysis of variance, followed
      by Duncan's test. Among all composite materials, expired composites presented
      lower cell viability than the non-expired composites over the three-day time
      period; the difference in survival rates between the expired and non-expired
      groups was statistically significant (P < 0.05). Non-expired Quadrant Universal
      LC demonstrated high survival rates, followed by Filtek Z250 and Alpha-dent at
      two and five days. It can be concluded that expiration dates have a significant
      effect on the cytotoxicity of the composite materials.

PMID- 21735870
TI  - Significance of cannabis use to dental practice.
AB  - The illicit use of the three main forms of cannabis-marijuana, hash, hash oil
      pose certain obstacles and challenges to the dental professional. There are a
      number of systemic, as well as oral/head and neck manifestations, associated with
      cannabis use. Dentists need to be aware of these manifestations in order to take
      whatever precautions and/or modifications to the proposed treatment that might be
      necessary.

PMID- 21735871
TI  - [Principles of controlled clinical trials].
AB  - The recovery of the patient should be facilitated as the result of therapeutic
      research. The basic rule for every therapeutic-clinical trial mist involve a
      comparison of therapeutic approaches. In acute conditions, such as acute
      infectious diseases, infarcts, etc., comparisons should be made between two or
      more groups: the collective therapeutic comparison = the between patients trial.
      The formation of groups, to be compared one with the other can be justified only
      if one is reasonably sure that a pathogenic condition indeed exists. In chronic
      diseases, which extend essentially unchanged over a lengthy period but are
      nevertheless reversible, therapeutic comparisons may be made between two or more
      time intervals within the course of the disease in the same individual. This type
      of therapeutic trial rests primarily upon a (refined!) type of specious reasoning
      and secondarily, upon modified statistics: the individual therapeutic comparison
      = the within patient trial. The collective therapeutic comparison, on the one
      hand, and the individual therapeutic comparison on the other, overlap somewhat in
      scope. The immediate therapeutic effect is not always an indication of its true
      value, which may become evident only upon long-term treatment. The short-term
      trials of therapeutic regimens in an individual must, therefore, be frequently
      supplemented by long-term trials which can only be carried out by comparing two
      groups. For many clinical investigations, therefore, the joint efforts of
      numerous hospitals are absolutely necessary. The second basic rule of therapeutic
      research is the elimination of secondary causes. The difficulties introduced by
      these secondary considerations are far greater in therapeutic trials carried out
      on ambulatory patients than has been hitherto realized. In order to remove
      subjective secondary causes, the author demanded, in 1931, the use of hidden or
      illusory media (placebos, dummies) that is, unconscious causative agents. The
      double blind procedure is indispensible in all experiments, especially where
      psychological processes and problems are of foremost importance. Therefore, it is
      absolutely necessary that convincing tests be finally carried out with the double
      blind procedure on the one hand, and the simple blind procedure on the other in
      order to determine the range and limitations of both. Therapeutic research of the
      future is threatened by the hazard of self-satisfaction which produces a sense of
      accomplishment merely as the result of obeying formal conditions and of following
      formal standards of accuracy.

PMID- 21735872
TI  - The organization of cooperative effort by multiple hospitals, exemplified by
      testing of therapeutic agents in rheumatoid arthritis.
AB  - The advantage of a multi-center clinical investigation lies in the possibility of
      obtaining conclusive results on the basis of relatively few numbers of patients
      from each of the participating institutions. It has the disadvantage of a lack of
      uniformity of methods among centers, which must be overcome by careful advance
      planning, including the institution of a central coordinating unit, the
      biometrical unit. Its functions include (1) participation in the planning of all
      phases of the investigation, (2) editing and processing of the data, and (3)
      analysis of the data and evaluation of results. Three devices for promoting
      uniformity of methods are: (1) the protocal, (2) specially designed record forms,
      and (3) visits to participating centers by a team of observers, including the
      statistician. The protocol is the document which contains all important
      specification for the conduct of the investigation, including statement of
      purpose of the study, definition of the study population, and explicit
      instructions on methods of patient assessment. In a clinical trial, the
      biometrical unit prepares the random allocation of treatments to patients.
      Stratification may be used to make comparisons between strata, and/or increase
      the sensitivity of the experiment. Stratification by exclusion may increase
      sensitivity at the cost of restricting the generality of results. A well-planned
      multi-center study, in which the members really cooperate, may achieve objectives
      exceeding the scope of single-center studies and provide a setting for the
      fruitful exchange of knowledge and ideas.

PMID- 21735873
TI  - Practical considerations in cooperative therapeutic trials.
AB  - Various practical problems associated with cooperative therapeutic trials are
      discussed from the experience obtained during the U. S. Veterans Administration
      Cooperative Study on Antihypertensive Agents. The problems discussed include
      stratification of patients on the basis of severity, methods and precautions for
      achieving double-blind therapeutic regimens, methods for obtaining uniformity of
      data in different hospitals, and the need for inserting modifications in the
      protocol to take care of the patients developing life threatening complications.
      Other practical problems discussed include the need for obtaining the cooperation
      of the ward physicians and the problem associated with defaulters and those who
      do not follow the prescribed regimens. Experimental design helps to restrict
      errors introduced by variance between hospitals. Cooperative trials have goals
      and use methods which are somewhat different from the classical methods and aims
      of laboratory research, and should be evaluated in their proper frame of
      reference.

PMID- 21735874
TI  - Mechanized processing and retrieval of bio-medical information.
AB  - A report is given on the mechanized information retrieval system in operation in
      the Abbott Laboratories' Science Information Services which is used for the
      biomedical periodical literature. The system uses a random 12-digit number coding
      system and an IBM Electronic Statistical Machine 101. The following subjects are
      discussed in detail: the dictionary; abstracting, coding, and machine searching
      procedure; uses of the Abbott Abstracts; limitations of the system, and future
      plans for an improved system.

PMID- 21735875
TI  - Experimental compound letter designations.
AB  - Most companies use a system of letters and numbers to identify their experimental
      compounds before they have a name. A list of over 250 of the letter designations
      used by various companies is presented.

PMID- 21735876
TI  - Controlled trials: nuisance or necessity?
AB  - Placebos can mimic in many ways the characteristics of active drugs. The
      importance of placebo controls in clinical trials in the evaluation of
      therapeutic efficacy and side action liability of drugs is exemplified by
      specific examples from human experimentation. It is concluded that controlled
      trials will prevent many of the errors inherent in uncontrolled therapeutic
      observations.

PMID- 21735877
TI  - [The planning of therapeutic trials in leukemias].
AB  - The planning of therapeutic trials in leukemias presents special problems due to
      the very variable spontaneous courses. The chronic forms are better accessible to
      an individual comparison. With the multitude of objective criteria relatively few
      difficulties arise if long enough periods of therapy are planned and performed.
      The criteria for the composition of homogeneous collectives as the basis for the
      much more difficult group comparison are discussed. In the absence of a
      subdivision into stages the duration of the past history can be used as a
      substitute criterion. Non-homogeneity in this regard leads to erroneous results,
      a practical example for which is given. Important is also the consideration of
      therapeutic and non-therapeutic contributory causes to be regarded already in the
      planning. The documentation of the findings should be made on special form
      sheets, a personal model of which is brought up for discussion. Finally the
      cooperation of several clinics in the therapeutic sector is discussed and the
      special problems of such a procedure outlined.

PMID- 21735878
TI  - Abstracting and indexing in the medical sciences.
AB  - Abstracts and indexes constitute the most popular means of assuring adequate
      retrieval of the many thousands of papers published every year in the ever
      expanding field of medicine. Different types of abstracts and indexes are
      available for different purposes and to meet varying user requirements. The
      problem of "keeping up" with developments in one's own field of endeavour can
      usually be solved by qualified abstractors. Most indexes serve the purpose of
      assuring the retrieval of pertinent documents. However, in order to retrieve
      specific pieces of information which are absolutely indispensible to the medical
      practitioner or scientist, a new approach is needed. This technique, which is
      termed the "combined index-abstract" method, has been employed successfully for
      the handling of a large body of specific items of information in a restricted
      area of experimental and clinical pharmacology.

PMID- 21735879
TI  - [An introduction into statistics on the causes of death].
AB  - The doctor has an obvious tendency to underestimate the medical value of
      statistics on mortality and the causes of death. He often holds the view that the
      share of the doctor in the notification of a death is only related to the
      necessity of obeying the law on the legal status of the individual. This point of
      view is entirely comprehensible. The doctor has been brought up to look solely at
      the individual's destiny as it is affected by disease. But disease is also a mass
      phenomenon: under similar circumstances it affects many individuals at the same
      time. The statistics of morbidity and mortality bring into relief factors that
      work together in the genesis of disease. It is true that sources of error often
      make the real meaning of statistics difficult to grasp. It requires special
      experience to avoid wrong conclusions. Nevertheless, for those who know how to
      make critical use of them, the statistics of mortality and the causes of death
      are an important store of general and social medical knowledge. The subject
      deserves more scientific attention than has been the case so far.

PMID- 21735880
TI  - Planning of a therapeutic comparison by consideration of objective and subjective
      responses.
AB  - Often in drug trials only the objective, or the subjective responses of the
      subjects are investigated, depending on the kind of drug. It is, however,
      desirable to check both the objective and the subjective responses in every drug
      trial. The investigation of the objective symptoms which is especially necessary
      in psycho-pharmacological trials, presents great difficulties. When a bodily
      function is found which reflects the emotional reactions which it is desired to
      investigate, it is necessary to plan the trial in a way that allows the results
      to be seen as proof of the effects of the drugs. Proposals for such a therapeutic
      trial are made. In the checking of the subjective responses the questionnaire is
      reckoned to be the best method. Problems of how the questionnaires are made and
      how they are used in the trials are discussed. By checking the subjective
      reactions, not only the side effects of the drug are demonstrated, but also their
      therapeutic effects. The author does not agree with the opinion that the double
      blind test is better than the single blind test in every case. Appropriate
      investigations should be made to clarify these questions.

PMID- 21735881
TI  - The Medical Literature Analysis and Retrieval System (MEDLARS) of the U. S.
      National Library of Medicine.

PMID- 21735882
TI  - [Drug injury; collection and documentation of data. Ideas and proposals as seen
      from the point of view of the medical organization].
AB  - A report is given on the experience of the Arzneimittelkommission der Deutschen
      Arzteschaft in collecting and evaluating adverse reactions on drugs, observed by
      practitioners and hospitals. It is the purpose of this register to minimize the
      risk of drug therapy by making the material available to doctors. The paper
      discusses how this can be accomplished best. It is not intended to use special
      methods of documentation or a statistical evaluation of the collected raw data.
      Such methods seem to be justified only for specific inquiries, which should be
      limited to serious questions.

PMID- 21735883
TI  - Patient safety informatics.

PMID- 21735884
TI  - Using the LOTCA to measure cultural and sociodemographic effects on cognitive
      cultural and sociodemographic effects on cognitive skills in two groups of
      children.

PMID- 21735885
TI  - Swede midge (Diptera: Cecidomyiidae), ten years of invasion of crucifer crops in
      North America.
AB  - The Swede midge, Contarinia nasturtii Kieffer (Diptera: Cecidomyiidae), a common
      insect pest in Europe, is a newly invasive pest in North America that constitutes
      a major threat to cruciferous vegetable and field crops. Since its first
      identification in Ontario, Canada, in 2000, it has rapidly spread to 65 counties
      in the provinces of Ontario and Quebec and has recently been found in canola (one
      of two cultivars of rapeseed, Brassica napus L. and Brassica campestris L.) in
      the central Prairie region where the majority of Canada's 6.5 million ha (16
      million acres) of canola is grown. The first detection of Swede midge in the
      United States was in 2004 in New York cabbage (Brassica oleracea L.), but it has
      now been found in four additional states. Here, we review the biology of Swede
      midge, its host plant range, distribution, economic impact, pest status, and
      management strategies. We provide insight into this insect's future potential to
      become an endemic pest of brassica crops in North America. We also proposed
      research needed to develop tactics for handling this invasive pest in brassica
      crops.

PMID- 21735886
TI  - Appropriateness of probit-9 in the development of quarantine treatments for
      timber and timber commodities.
AB  - Following the increasing international phasing out of methyl bromide for
      quarantine purposes, the development of alternative treatments for timber pests
      becomes imperative. The international accreditation of new quarantine treatments
      requires verification standards that give confidence in the effectiveness of a
      treatment. Probit-9 mortality is a standard for treatment effectiveness that has
      its origin in fruit fly research, and has been adopted by the United States
      Department of Agriculture for fruit flies and several other pests. Following
      this, the probit-9 standard has been adopted as a benchmark for many quarantine
      treatments worldwide. This article discusses aspects of the application of this
      concept for a range of timber pests. Problematic issues include the often small
      pest populations available for testing, the limits of modeling pest responses to
      a treatment in the absence of sufficient numbers for treatment verification, the
      species diversity of pests and host materials and the physical and chemical
      conditions of host material or treatment conditions. Where treatment verification
      by killing large numbers of individuals is impossible, data collected from small
      populations or under specific conditions must be interpreted with caution. We
      discuss possible alternative approaches to probit-9 as a treatment efficacy
      standard.

PMID- 21735887
TI  - Cross-species infection of deformed wing virus poses a new threat to pollinator
      conservation.
AB  - The Deformed wing virus (family Iflaviridae, genus Iflavirus, DWV), one of the
      most prevalent and common viruses in honey bees, Apis mellifera L., is present in
      both laboratory-reared and wild populations of bumble bees, Bombus huntii Greene.
      Our studies showed that DWV infection spreads throughout the entire body of B.
      huntii and that the concentration of DWV is higher in workers than in males both
      collected in the field and reared in the laboratory, implying a possible
      association between the virus infection and foraging activities. Further results
      showed that gut tissue of B. huntii can support the replication of DWV,
      suggesting that B. huntii is a biological host for DWV, as are honey bees. Bumble
      bees and honey bees sometimes share nectar and pollen resources in the same
      field. The geographical proximity of two host species probably plays an important
      role in host range breadth of the virus.

PMID- 21735888
TI  - Role of relative humidity in colony founding and queen survivorship in two
      carpenter ant species.
AB  - Conditions necessary for optimal colony foundation in two carpenter ant species,
      Camponotus modoc Wheeler and Camponotus vicinus Mayr, were studied. Camponotus
      modoc and C. vicinus queens were placed in Douglas-fir, Pseudotsuga menziesii
      (Mirb. Franco) and Styrofoam blocks conditioned in sealed chambers at 70, 80, or
      100% RH. Nanitic workers produced after 12 wk were used to assess the effects of
      substrate and moisture content on colony initiation. Queens of C. vicinus in
      Douglas-fir and Styrofoam produced worker numbers that did not differ
      significantly with moisture content; however, the number of colonies initiated by
      C. modoc differed significantly with moisture content. The results indicate that
      colony founding in C. vicinus is less sensitive to moisture content than C. modoc
      for Douglas-fir and Styrofoam. In another test, groups of queens of each species
      were exposed to 20, 50, 70, and 100% RH and the time until 50% mortality occurred
      was recorded for each species. C. vicinus lived significantly longer at each of
      the test humidities than C. modoc, suggesting that the former species is adapted
      to better survive under xeric conditions.

PMID- 21735889
TI  - Expression of Varroa sensitive hygiene (VSH) in commercial VSH honey bees
      (Hymenoptera: Apidae).
AB  - We tested six commercial sources of honey bees, Apis mellifera L. (Hymenoptera:
      Apidae), whose breeding incorporated the trait of Varroa sensitive hygiene (VSH).
      VSH confers resistance to the parasitic mite Varroa destructor Anderson & Trueman
      by enhancing the ability of the bees to hygienically remove mite-infested brood.
      VSH production queens (i.e., queens commercially available for use in beekeepers'
      production colonies) from the six sources were established in colonies which
      later were measured for VSH. Their responses were compared with those of colonies
      with three other types of queens, as follows: VSH queens from the selected closed
      population maintained by USDA-ARS for research and as a source of breeding
      germplasm, queens from the cooperating commercial distributor of this germplasm,
      and queens of a commercial, mite-susceptible source. The reduction of mite
      infestation in brood combs exposed to test colonies for 1 wk differed
      significantly between groups. On average, colonies with VSH production queens
      reduced infestation by 44%. This group average was intermediate between the
      greater removal by pure ARS VSH (76%) and the cooperators' breeding colonies
      (64%), and the lesser removal by susceptible colonies (7%). VSH production
      colonies from the different sources had variable expression of hygiene against
      mites, with average reduced infestations ranging from 22 to 74%. In addition,
      infertility was high among mites that remained in infested cells in VSH breeder
      colonies from ARS and the commercial distributor but was lower and more variable
      in VSH production colonies and susceptible colonies. Commercial VSH production
      colonies supply mite resistance that generally seems to be useful for beekeeping.
      Resistance probably could be improved if more VSH drones sources were supplied
      when VSH production queens are being mated.

PMID- 21735890
TI  - Influence of rough handling on Osmia lignaria (Hymenoptera: Megachilidae) nest
      establishment in commercial orchards.
AB  - Osmia lignaria Say (Hymenoptera: Megachilidae) can be used to pollinate fruit
      trees. Populations are sometimes difficult to sustain because some female bees
      fail to establish at provided nesting sites. We address the hypothesis that rough
      handling of overwintered O. lignaria results in decreased establishment. We
      tested this by shaking (200 rpm for 2 min) overwintering bees as a proxy for
      rough handling. Bees were then released in an orchard, and nest establishment of
      shaken and unshaken bees was recorded. There was no significant difference in the
      proportion of shaken and unshaken females that nested, indicating that rough
      handling of overwintering bees does not discourage nest establishment.

PMID- 21735891
TI  - The effects of temperature, diet, and other factors on development, survivorship,
      and oviposition of Aethina tumida (Coleoptera: Nitidulidae).
AB  - Developmental rate and survivorship of small hive beetle, Aethina tumida Murray
      (Coleoptera: Nitidulidae), life stages were measured across different
      temperatures (21, 25, 28, 32 and 35 degrees C) and diets, which included natural
      and artificial pollen, honey, and bee pupae. Temperature affected hatch success,
      time to hatching, and larval growth. Eggs hatched in 61 h at 21 degrees C but in
      < 22 h at 35 degrees C. Larvae achieved peak weight in < 8 d at 35 degrees C but
      needed 17 d at 21 degrees C. Diet had comparatively little effect on larval
      survivorship or maximum weight, although larvae fed only bee pupae had lower
      survivorship. Access to soil influenced pupation success. Duration of the life
      stage spent in the soil, during which pupation occurs, was also affected by
      temperature: adults emerged after 32.7 d at 21 degrees C but after only 14.8 d at
      35 degrees C, albeit with high mortality. Minimum temperature for development was
      estimated at 13.5 degrees C for eggs, and 10.0 degrees C for larvae and pupae.
      Temperature influenced adult longevity and oviposition: on a honey and pollen
      diet average adult lifespan was 92.8 d at 24 degrees C but only 11.6 d at 35
      degrees C. Beetles lived longer at 28 degrees C or lower but produced the most
      eggs per female, regardless of diet, at 32 degrees C. Beetle density influenced
      fecundity: beetles kept at three pairs per vial laid 6.7 times more eggs per
      female than those kept as single pairs. Overall, beetles fared best at 28-32
      degrees C with mortality of all stages highest at 35 degrees C.

PMID- 21735892
TI  - The stock of invasive insect species and its economic determinants.
AB  - Invasions of nonindigenous organisms have long been linked to trade, but the
      contribution of individual trade pathways remains poorly understood, because
      species are not observed immediately upon arrival and the number of species
      arriving annually is unknown. Species interception records may count both new
      arrivals and species long introduced. Furthermore, the stock of invasive insect
      species already present is unknown. In this study, a state-space model is used to
      infer the stock of detected as well as undetected invasive insect species
      established in the United States. A system of equations is estimated jointly to
      distinguish the patterns of introduction, identification, and eradication.
      Introductions of invasive species are modeled as dependent on the volume of trade
      and arrival of people. Identifications depend on the public efforts at invasive
      species research, as well as on the established stock of invasive species that
      remain undetected. Eradications of both detected and undetected invasive species
      depend on containment and quarantine efforts, as well as on the stock of all
      established invasive species. These patterns are estimated by fitting the
      predicted number of invasive species detections to the observed record in the
      North American Non-Indigenous Arthropod Database. The results indicate that
      agricultural imports are the most important pathway of introduction, followed by
      immigration of people. Expenditures by the U.S. Department of Agriculture and the
      Agricultural Research Service are found to explain the species identification
      record well. Between three and 38 invasive insect species are estimated to be
      established in the United States undetected.

PMID- 21735893
TI  - Compatibility of two systemic neonicotinoids, imidacloprid and thiamethoxam, with
      various natural enemies of agricultural pests.
AB  - Two systemic neonicotinoids, imidacloprid and thiamethoxam, are widely used for
      residual control of several insect pests in cotton (Gossypium spp.), vegetables,
      and citrus (Citrus spp.). We evaluated their impact on six species of beneficial
      arthropods, including four parasitoid species--Aphytis melinus Debach,
      Gonatocerus ashmeadi Girault, Eretmocerus eremicus Rose & Zolnerowich, and
      Encarsia formosa Gahan--and two generalist predators--Geocoris punctipes (Say)
      and Orius insidiosus (Say)--in the laboratory by using a systemic uptake
      bioassay. Exposure to systemically treated leaves of both neonicotinoids had
      negative effects on adult survival in all four parasitoids, with higher potency
      against A. melinus as indicated by a low LC50. Mortality was also high for G.
      ashmeadi, E. eremicus, and E. formosa after exposure to both compounds but only
      after 48 h posttreatment. The two predators G. punctipes and O. insidiosus were
      variably susceptible to imidacloprid and thiamethoxam after 96-h exposure.
      However, toxicity to these predators may be related to their feeding on foliage
      and not just contact with surface residues. Our laboratory results contradict
      suggestions of little impact of these systemic neonicotinoids on parasitoids or
      predators but field studies will be needed to better quantify the levels of such
      impacts under natural conditions.

PMID- 21735894
TI  - Insecticides suppress natural enemies and increase pest damage in cabbage.
AB  - Intensive use of pesticides is common and increasing despite a growing and
      historically well documented awareness of the costs and hazards. The benefits
      from pesticides of increased yields from sufficient pest control may be
      outweighed by developed resistance in pests and killing of beneficial natural
      enemies. Other negative effects are human health problems and lower prices
      because of consumers' desire to buy organic products. Few studies have examined
      these trade-offs in the field. Here, we demonstrate that Nicaraguan cabbage
      (Brassica spp.) farmers may suffer economically by using insecticides as they get
      more damage by the main pest diamondback moth, Plutella xylostella (L.)
      (Lepidoptera: Plutellidae), at the same time as they spend economic resources on
      insecticides. Replicated similarly sized cabbage fields cultivated in a
      standardized manner were either treated with insecticides according common
      practice or not treated with insecticides over two seasons. Fields treated with
      insecticides suffered, compared with nontreated fields, equal or, at least in
      some periods of the seasons, higher diamondback moth pest attacks. These fields
      also had increased leaf damage on the harvested cabbage heads. Weight and size of
      the heads were not affected. The farmers received the same price on the local
      market irrespective of insecticide use. Rates of parasitized diamondback moth
      were consistently lower in the treated fields. Negative effects of using
      insecticides against diamondback moth were found for the density of parasitoids
      and generalist predatory wasps, and tended to affect spiders negatively. The
      observed increased leaf damages in insecticide-treated fields may be a combined
      consequence of insecticide resistance in the pest, and of lower predation and
      parasitization rates from naturally occurring predators that are suppressed by
      the insecticide applications. The results indicate biological control as a viable
      and economic alternative pest management strategy, something that may be
      particularly relevant for the production of cash crops in tropical countries
      where insecticide use is heavy and possibly increasing.

PMID- 21735895
TI  - Approved quarantine treatment for Hessian fly (Diptera: Cecidomyiidae) in large
      size hay bales and Hessian fly and cereal leaf beetle (Coleoptera: Chrysomelidae)
      control by bale compression.
AB  - A quarantine treatment using bale compression (32 kg/cm2 pressure) and phosphine
      fumigation (61 g/28.3 m3 aluminum phosphide for 7 d at 20 degrees C) was approved
      to control Hessian fly, Mayetiola destructor (Say), in large-size, polypropylene
      fabric-wrapped bales exported from the western states to Japan. No Hessian fly
      puparia (45,366) survived to the adult stage in infested wheat, Triticum aestivum
      L., seedlings exposed to the treatment in a large-scale commercial test. Daily
      temperatures (mean +/- SEM) inside and among bales in three test freight
      containers were 17.8 +/- 0.2 front top, 17.0 +/- 0.2 front bottom, 17.3 +/- 0.2
      middle bale, 15.7 +/- 0.3 middle air, 18.5 +/- 0.1 back top, and 18.1 +/- 0.1
      degrees C back bottom, allowing the fumigation temperature to be established at >
      or = 20 degrees C. Mean fumigant concentrations ranged from 208 to 340 ppm during
      the first 3 d and ranged from 328 to 461 ppm after 7 d of fumigation. Copper
      plate corrosion values inside the doors, and in the middle of the large-size
      bales in all locations indicated moderate exposure to hydrogen phosphide (PH3).
      PH3 residues were below the U.S. Environmental Protection Agency tolerance of 0.1
      ppm in animal feeds. The research was approved by Japan and U.S. regulatory
      agencies, and regulations were implemented on 20 May 2005. Compression in large
      size bale compressors resulted in 3-3.6 and 0% survival of Hessian fly puparia
      and cereal leaf beetle, Oulema melanopus (L.), respectively. Bale compression can
      be used as a single treatment for cereal leaf beetle and as a component in a
      systems approach for quarantine control of Hessian fly.

PMID- 21735896
TI  - Effect of temperature on life table parameters of predatory thrips Scolothrips
      longicornis (Thysanoptera: Thripidae) fed on twospotted spider mites (Acari:
      Tetranychidae).
AB  - Environmental variables such as temperature are important factors that affect the
      efficiency of biological control agents. This study examined the effect of
      temperature on the sex ratio, longevity, oviposition periods, fecundity and life
      table parameters of the predatory thrips Scolothrips longicornis Priesner
      (Thysanoptera: Thripidae) fed on twospotted spider mite, Tetranychus urticae Koch
      (Acari: Tetranychidae), at six constant temperatures: 15, 20, 26, 30, 35, and 37
      degrees C. Approximately 75% of the progeny were female, except at 37 degrees C,
      at which temperature the proportion of males increased. Adult longevity as well
      as the preoviposition, oviposition, and postoviposition periods decreased
      significantly with temperature. Thus, adults lived for approximately 5 wk at 15
      degrees C and < 1 wk at 37 degrees C with preoviposition, oviposition, and
      postoviposition periods ranging from 6.4 to 0.4, 24.4-3.1, and 7-0.8 d between
      the two temperature extremes, respectively. The maximum (56.48 eggs) and minimum
      (11.69 eggs) value of total fecundity was recorded at 26 and 37 degrees C,
      respectively. The intrinsic rate of natural increase (r(m)) of S. longicornis
      increased linearly with increasing temperature from 0.056 d(-1) at 15 degrees C
      to 0.310 d(-1) at 35 degrees C. The lower temperature threshold for the
      population increase of S. longicornis was estimated to be around 5 degrees C. The
      data suggest that the upper temperature threshold for the predatory thrips is
      approximately 37 degrees C. The results showed that populations of S. longicornis
      are able to develop at a broad range of temperatures and that this predator is
      well adapted to the high temperatures that occur in the Mediterranean region.

PMID- 21735897
TI  - Feeding behavior of neonate Ostrinia nubilalis (Lepidoptera: Crambidae) on Cry1Ab
      Bt corn: implications for resistance management.
AB  - The European corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae), is
      an economically important insect pest of corn, Zea mays L., in the United States
      and Canada. The development of genetically modified corn expressing genes derived
      from Bacillus thuringiensis (Bt) that encodes insecticidal crystalline (Cry)
      proteins has proven to be effective in controlling this insect. To assess the
      feeding behavior of neonate O. nubilalis on Bt corn, we examined differences in
      feeding behavior, based on presence of plant material in the gut, between Cry1Ab
      Bt corn and non-Bt near isoline corn for four intervals over a 48-h period.
      Feeding experiments revealed that there was significantly less feeding on Bt corn
      compared with non-Bt near isoline corn. The behavior of neonates on the plant
      corresponded with the differences in feeding on the two corn lines. The findings
      also showed that > 50% of the larvae initially left the plant before there was
      evidence in the gut of feeding regardless of whether the source was Bt or non-Bt
      corn. A higher quantity of plant material was found in the gut of larvae
      recovered from leaves of non-Bt compared with Bt corn. At the end of 48 h among
      the larvae that had left the plant, a greater proportion from Bt corn had plant
      material in the gut than did those from non-Bt corn.

PMID- 21735898
TI  - Quality of mass-reared codling moth (Lepidoptera: Tortricidae) after long
      distance transportation: 1. Logistics of shipping procedures and quality
      parameters as measured in the laboratory.
AB  - The sterile insect technique (SIT) is a proven effective control tactic against
      lepidopteran pests when applied in an areawide integrated pest management
      program. The construction of insect mass-rearing facilities requires considerable
      investment and moth control strategies that include the use of sterile insects
      could be made more cost-effective through the importation of sterile moths
      produced in other production centers. For codling moth, Cydia pomonella (L.)
      (Lepidoptera: Tortricidae), this is an attractive option because mating studies
      have confirmed the absence of mating barriers between codling moth populations
      from geographically different areas. To assess the feasibility of long-distance
      transportation of codling moths, pupae and adult moths were transported in 2004
      from Canada to South Africa in four shipments by using normal commercial
      transport routes. The total transport time remained below 67 h in three of the
      consignments, but it was 89 h in the fourth consignment. Temperature in the
      shipping boxes was fairly constant and remained between -0.61 and 0.16 degrees C
      for 76.8-85.7% of the time. The data presented indicate that transporting codling
      moths as adults and pupae from Canada to South Africa had little effect on moth
      emergence, longevity, and ability to mate, as assessed in the laboratory. These
      results provide support to the suggestion that the STT for codling moth in pome
      fruit production areas might be evaluated and implemented by the importation of
      irradiated moths from rearing facilities in a different country or hemisphere.

PMID- 21735899
TI  - Chirality and bioactivity of the sex pheromone of Madeira mealybug (Hemiptera:
      Pseudococcidae).
AB  - Two compounds (trans-1R,3R-chrysanthemyl R-2-methylbutanoate and R-lavandulyl R-2
      methylbutanoate) identified from aeration extracts of virgin female Madeira
      mealybug, Phenacoccus madeirensis Green (Hemiptera: Pseudococcidae), were
      synthesized and tested in field bioassays in northern Taiwan over a 1-mo period.
      In total, 1,492 male P. madeirensis were captured in sticky traps. Our results
      showed that 1 microg of synthetic trans-1R,3R-chrysanthemyl R-2-methylbutanoate
      released from a plastic tube dispenser was attractive to the mealybugs. Different
      stereoisomers of chrysanthemyl 2-methylbutanoate also were tested. The insect
      produced stereoisomer was the most attractive of all the isomers tested, and the
      stereochemistry of the acid moiety proved to be more critical than that of the
      alcohol moiety. The minor component found in extracts, R-lavandulyl R-2
      methylbutanoate, alone was not attractive to male Madeira mealybugs nor did it
      act synergistically or additively with the main component.

PMID- 21735900
TI  - Effects of cadmium exposure on lipid peroxidation and the antioxidant system in
      fourth-instar larvae of Propsilocerus akamusi (Diptera: Chironomidae) under
      laboratory conditions.
AB  - Enzymatic antioxidants such as selenium-dependent glutathione peroxidase (GPx),
      glutathione transferase (GST), glutathione reductase (GR), and superoxide
      dismutases (SOD), as well as the concentration of hydrogen peroxide (H2O2) and
      malondialdehyde (MDA, an indicator of lipid peroxidation) were determined to
      identify which antioxidant enzymes participate in the efficient scavenging of ROS
      generated upon exposure to high doses of Cd2+ in fourth-instar Propsilocerus
      akamusi (Tokuna) (Diptera: Chironomidae) larvae after 72-h exposure. A
      significant increase in MDA levels and a change in GR and GPx activities in the
      Cd(2+)-treated P. akamusi were observed. The MDA in 25.0 and 50.0 mmol/liter
      treatments was significantly higher than that of the control dose after 72 h
      exposure. GPx activity was significantly induced by Cd2+ exposure only in the
      50.0-mmol/liter treatment with a 0.59-fold increase in the control. All doses of
      Cd2+ significantly suppressed GR activity compared with the findings for the
      control dose, with an inhibited rate up to 0.55-fold in the 25.0 mmol/liter Cd2+
      treatment. SOD and GST activities were not altered. The results indicate that
      Cd2+ can induce oxidative stress as indicated by the changes in lipid
      peroxidation and antioxidant status. For P. akamusi, an increase in the dose that
      the threshold needed for defense (namely, MDA level and GPx activity) activation
      was achieved. From this, organisms can be hypothesized to enable cells to avoid
      oxidant stress up to a certain extent where damage is again measurable (higher
      Cd2+ concentration).

PMID- 21735901
TI  - Sublethal effects of imidacloprid on Bemisia tabaci (Hemiptera: Aleyrodidae)
      under laboratory conditions.
AB  - The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is
      one of the most important pests in tropical and subtropical agriculture and is a
      key pest in greenhouse production worldwide. Current management of B. tabaci
      relies upon frequent applications of insecticides. Insecticide use not only
      directly affects pest populations through acute toxicity but also has indirect
      (sublethal) effects on pest physiology or behavior. In this study, we described
      sublethal effects of imidacloprid on adult feeding, immature development, adult
      fecundity, and F1 development of B. tabaci. Honeydew excretion of adults feeding
      on leaves treated with LC20 and LC40 concentration was significantly lower than
      that on untreated leaf discs. Egg production of B. tabaci adults subject to LC20
      and LC40 concentrations also was less than untreated individuals. Upon transfer
      to untreated leaves, honeydew excretion and egg production recovered well within
      24 and 48 h, respectively. Exposure to LC20 and LC40 concentrations significantly
      affected developmental time of B. tabaci eggs and nymphs, whereas it did not
      affect adult molting rate. We did not find sublethal effects on longevity and
      fecundity of B. tabaci adults when exposed to LC90 and LC40 concentrations for 24
      h, and on egg hatching rate, nymphal mortality, and molting rate of the
      subsequent F1 generation. Exposure to imidacloprid at LC40 concentration
      significantly decreased the number of females in the F1 generation. Imidacloprid
      negatively affects development and reproduction of exposed individuals, and sex
      ratio of subsequent (F1) generation of B. tabaci, which probably disrupts B.
      tabaci population dynamics, slows population increase, and reduces infestation
      levels. Therefore, it is necessary to consider potential impact from imidacloprid
      for integrated management of the pest.

PMID- 21735902
TI  - Control of mushroom sciarid fly Lycoriella ingenua populations with insect growth
      regulators applied by soil drench.
AB  - Mushroom sciarid fly Lycoriella ingenua (Dufour, 1839) comb. nov., is one of the
      most common fly pests affecting the cultivation of Agaricus bisporus (Lange)
      Imbach in Turkey. In this study, eight insect growth regulators (IGRs)-
      diflubenzuron, flufenoxuron, lufenuron, methoprene, novaluron, pyriproxyfen,
      teflubenzuron, and triflumuron-were tested for their potential to control L.
      ingenua populations in two successive growing periods. Treatments were targeted
      at larvae as soil drenches; treatment efficacy was evaluated by assessing adult
      emergence and larval damage. These products were compared with a control treated
      with water (negative control) and a conventional chemical insecticide
      (chlorpyrifos ethyl) (positive control). Treatments with the IGRs caused
      significant reductions in emerging adult numbers and sporophore damage rates
      compared with the water-treated control over the two growing periods. Of the IGRs
      tested, novaluron, diflubenzuron, and teflubenzuron had significantly lower
      numbers of emerging adults than the rest of the IGRs and chlorpyrifos ethyl
      treated control in both periods. Treatments with teflubenzuron, pyriproxyfen,
      novaluron, and diflubenzuron resulted in significantly lower sporophore damage
      rates than all other treatments. Compared with negative control, there were no
      significant yield reductions due to applications of selected IGRs. The results
      suggest that all the IGRs tested can be used as alternatives to conventional
      pesticides in controlling L. ingenua populations on mushroom.

PMID- 21735903
TI  - What is the economic threshold of soybean aphids (Hemiptera: Aphididae) in enemy
      free space?
AB  - Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is a serious pest
      of soybean, Glycine max (L.) Merr., in the North Central United States. Current
      management recommendations rely on the application of insecticides based on an
      economic threshold (ET) of 250 aphids per plant. Natural enemies are important in
      slowing the increase of aphid populations and can prevent them from reaching
      levels that can cause economic losses. However, biological control of A. glycines
      is inconsistent and can be affected negatively by the intensity of agricultural
      activity. We measured the impact of a natural-enemy-free environment on the
      capacity of the current ET to limit yield loss. In 2008 and 2009, caged
      microplots were assigned to one of three treatments: plants kept aphid-free
      (referred to as the control), plants that experienced a population of 250 aphids
      per plant (integrated pest management [IPM]), and plants that experienced
      unlimited aphid population growth (unlimited). The population growth rate of
      aphids in the unlimited treatment for the 10 d after the application of
      insecticides to the IPM treatment was calculated using linear regression. The
      linear equation was solved to determine the mean number of days between the ET
      and the EIL for an aphid population in absence of predators. The number of days
      was determined to be 6.97 +/- 1.11 d. The 2-yr average yield for the IPM
      treatment was 99.93% of the control treatment. Our study suggests the current
      soybean aphid ET of 250 aphids per plant can effectively protect yield even if
      the impact of natural enemies is reduced.

PMID- 21735904
TI  - Modification of hormonal balance in larvae of the corn borer Sesamia nonagrioides
      (Lepidoptera: Noctuidae) due to sublethal Bacillus thuringiensis protein
      ingestion.
AB  - Bacillus thuringiensis (Bt) corn, Zea mays L., is highly efficient against the
      corn borer Sesamia nonagrioides (Lefebvre) (Lepidoptera: Noctuidae) when the
      larvae feed only on the transgenic plants. However, when they feed on Bt leaves
      during only part of their development, thus ingesting sublethal amounts of Bt
      toxins, some larvae survive. A previous study reported a prolonged development
      and precocious diapause induction in larvae fed on a diet with sublethal amounts
      of Cry1Ab protein. To determine whether these effects were accompanied by a
      modification of the hormonal balance, S. nonagrioides larvae were fed on
      sublethal amounts of Bt protein provided in Bt leaves or in the diet. The larvae
      that survived had higher levels of juvenile hormone (JH), whereas their level of
      ecdysteroids did not increase sufficiently to allow pupation, leading to a longer
      larval development and more larval molts. This response may be considered a
      defense mechanism that allows some larvae to survive toxin ingestion; it is
      similar the response to insecticidal toxins or viruses observed in other larvae.
      Changes in the hormone levels in diapausing larvae were undetectable, probably
      because these changes were masked by the higher level of JH in the hemolymph of
      diapausing larvae and because of lack of ecdysteroid titer increase, a phenomenon
      that is usually observed a few days before pupation in nondiapausing larvae.
      These results should be taken into account in the establishment of non-Bt refuges
      to prevent development of Bt-resistance in S. non-agrioides populations.

PMID- 21735905
TI  - Effect of wood hardness and secondary compounds on feeding preference of
      Odontotermes formosanus (Isoptera: Termitidae).
AB  - Odontotermes formosanus (Shiraki) (Isoptera: Termitidae) is one of the most
      destructive plant pests in China, which control relies mainly on baits
      strategies. Baits made from the wood of eight different tree species were used to
      study the feeding preference of this termite, and conversely wood protection
      strategies of the tree species. Three bait types were used to identify wood
      protection strategies: solid wood (physical and chemical protection), crude flour
      (chemical protection) made from ground wood, and extracted flour (no protection)
      made by extracting crude flour with ethanol and toluene. Feeding preference was
      influenced by wood species and bait type. For solid wood, Magnolia denudata Desr
      (75%) and Elaeocarpus glabripetalus Merr (41%) were most preferred; for crude
      flour, E. glabripetalus (97%) and Quercus variabilis Blume (92%) were most
      preferred; and for extracted flour, there were no significant differences between
      wood species, demonstrating the influence of chemical defense. The greatest
      contrast between bait types was for Platanus orientalis L, the least preferred as
      solid wood and crude flour, suggesting that chemical defense compounds are
      particularly important in this species. Solid wood consumption was inversely
      correlated with wood density. Extracted flour consumption was positively
      correlated with glucose concentration. There was no direct effect of
      holocellulose and other components tested. O. formosanus preferred to fed on soft
      wood with low chemical protection (M. denudata); conversely trees protected their
      wood either physically [e.g., E. glabripetalus, Q. variabilis, Cinnamomum
      camphora (L.) Presl, and Ligustrum lucidum Aiton] or chemically (Populus bonati
      Levl) or a combination of both strategies (Liquidamba formosana Hance and P.
      orientalis).

PMID- 21735906
TI  - Effects of fertilizer and low rates of imidacloprid on Adelges tsugae (Hemiptera:
      Adelgidae).
AB  - Healthy hemlock trees, Tsuga canadensis (L.) Carriere, and hemlock woolly
      adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae), populations should favor
      retention and population growth of adelgid predators such as Laricobius nigrinus
      Fender (Coleoptera: Derodontidae) and Sasajiscymnus tsugae (Sasaji & McClure)
      (Coleoptera: Coccinellidae). Eastern hemlock trees between 15 and 38 cm diameter
      at breast height (dbh) were treated with 0, 10, or 25% of 1.5 g imidacloprid
      (Merit 75 WP) per 2.5 cm dbh and were either fertilized or not, in a 3 by 2
      factorial design. After 2 yr, imidacloprid reduced the numbers of ovisacs and
      eggs found on trees in a dosage-dependent manner, while enhancing tree growth
      parameters such as new shoots or needles and the length of new shoots. Fertilized
      trees had greater adelgid fecundity, which was positively correlated with total
      foliar N in both winter generations. In February 2009 (27 mo after imidacloprid
      treatment), higher imidacloprid dosages to unfertilized trees resulted in reduced
      adelgid fecundity. Concentrations of N, P, and K were higher in the foliage of
      trees treated with insecticide, whereas foliar aluminum concentrations were
      consistently lower in trees with higher insecticide dosages. Trees treated with
      low rates of imidacloprid were healthier than untreated trees, but only trees
      treated with the 0.1 x dosage had sufficient adelgids to possibly sustain
      predators over extended periods.

PMID- 21735907
TI  - Effects of habitat type and trap placement on captures of bark (Coleoptera:
      Scolytidae) and longhorned (Coleoptera: Cerambycidae) beetles in semiochemical
      baited traps.
AB  - Two studies were conducted to determine the effect of habitat selection and trap
      placement on catches of Scolytidae and Cerambycidae (Coleoptera) in northeastern
      U.S. forests. In a nonreplicated case study, four habitat types--closed canopy
      hardwood stand, closed canopy conifer stand, a low-intensity thinned Pinus
      strobus L. stand, and a high-intensity thinned P. strobus stand--were surveyed
      using alpha-pinene, ethanol, ipsenol, ipsdienol, and lanierone. Average trap
      catches, species richness, and the number of unique species captured were all
      highest in at least one of the thinned habitats. A second experiment that was
      replicated evaluated the placement of traps in relation to habitat patches.
      Semiochemical-baited traps (alpha-pinene and ethanol) were placed under a closed
      canopy forest, along an edge, and in a clearing and tested for effects on
      Scolytidae and Cerambycidae trap catches. Abundance and species richness were
      generally higher in the closed canopy and edge placements compared with traps in
      the open area. The highest number of unique species were captured in the edge and
      clearing.

PMID- 21735908
TI  - Evaluation of insecticides for control of overwintering Hylurgopinus rufipes
      (Coleoptera: Curculionidae).
AB  - A bark disk bioassay was used to assess the effectiveness of different
      insecticides for control of overwintering adult native elm bark beetles,
      Hylurgopinus rufipes (Eichoff) (Coleoptera: Curculionidae). Insecticides were
      applied to the base of the trunks of living American elm trees, Ulmus americana
      L., and bark disk samples were removed at intervals with a hole saw. Adult H.
      rufipes were exposed in bioassay chambers for which the bark disks formed the
      floor of the chamber. In September 2005, chlorpyrifos, permethrin, and a water
      control were applied to trees in five replicated blocks, and bark disk samples
      were taken at intervals over the following 725 d. In September 2006,
      chlorpyrifos, permethrin, carbaryl, bifenthrin, and a water control were applied
      to trees in six replicated blocks, and disk samples were removed at intervals up
      to 1,163 d after application. In both experiments, beetle mortality was 100% on
      chlorpyrifos-treated disks removed up to 725 d after treatment and, in the 2006
      trial, declined thereafter. The pattern of mortality in the bifenthrin treatment
      did not differ significantly from that in the chlorpyrifos treatment in the 2006
      experiment. Average corrected mortality on disks treated with permethrin or
      carbaryl declined below 100% by 11 d after application. On disks removed in the
      May following treatment, 248 d after application, average corrected mortality was
      42-44% on permethrin-treated disks and 26% on carbaryl-treated disks.

PMID- 21735909
TI  - Variation in enantiospecific attraction of Ips avulsus (Coleoptera:
      Curculionidae) to the pheromone ipsdienol in Georgia.
AB  - In 2006, we tested the responses of the small southern pine engraver, Ips avulsus
      (Eichhoff) (Coleoptera: Curculionidae), to multiple-funnel traps baited with (+)
      , (-)-, and (+/-)-ipsdienol. Three experiments were conducted in Georgia with all
      traps co-baited with one of the following lure combinations, respectively:
      experiment 1, ipsenol; experiment 2, lanierone and (-)-alpha-pinene; and
      experiment 3, ipsenol, lanierone, and (-)-alpha-pinene. Ipsdienol and lanierone
      are aggregation pheromones used by I. avulsus, whereas ipsenol is an aggregation
      pheromone used by the eastern fivespined ips, Ips grandicollis (Eichhoff), a
      sympatric species also breeding in pines. In all experiments, the highest catches
      of I. avulsus were obtained in traps baited with (+/-)-ipsdienol. The relative
      attractiveness of (+)-ipsdienol varied across the three experiments. When traps
      were co-baited with ipsenol, lanierone, and (-)-alpha-pinene, catches of I.
      avulsus in traps baited with (+)-ipsdienol were high and no different from those
      in traps baited with (+/-)-ipsdienol. When traps were co-baited with lanierone
      and (-)-alpha-pinene, catches in traps baited with (+)-ipsdienol were lower than
      those in traps baited with (+/-)-ipsdienol by approximately 40%, whereas catches
      were reduced by approximately 95% when traps were co-baited with ipsenol alone.
      We hypothesize that the observed variation in enantiospecific responses of I.
      avulsus to ipsdienol may be explained by variation in semiochemical context
      (i.e., different co-baits among the experiments) or seasonal variation.

PMID- 21735910
TI  - Efficacy of multifunnel traps for capturing emerald ash borer (Coleoptera:
      Buprestidae): effect of color, glue, and other trap coatings.
AB  - Tens of thousands of adhesive-coated purple prism traps are deployed annually in
      the United States to survey for the invasive emerald ash borer, Agrilus
      planipennis Fairmaire (Coleoptera: Buprestidae). A reusable, more user-friendly
      trap is desired by program managers, surveyors, and researchers. Field assays
      were conducted in southeastern Michigan to ascertain the feasibility of using
      nonsticky traps as survey and detection tools for emerald ash borer. Three
      nonsticky trap designs, including multifunnel (Lindgren), modified intercept
      panel, and drainpipe (all painted purple) were compared with the standard purple
      prism trap; no statistical differences in capture of emerald ash borer adults
      were detected between the multifunnel design and the prism. In subsequent color
      comparison assays, both green- and purple-painted multifunnel traps (and later,
      plastic versions of these colors) performed as well or better than the prism
      traps. Multifunnel traps coated with spray-on adhesive caught more beetles than
      untreated traps. The increased catch, however, occurred in the traps' collection
      cups and not on the trap surface. In a separate assay, there was no significant
      difference detected between glue-coated traps and Rain-X (normally a glass
      treatment)-coated traps, but both caught significantly more A. planipennis adults
      than untreated traps.

PMID- 21735911
TI  - Evaluation of yellow rectangle traps coated with hot melt pressure sensitive
      adhesive and sticky gel against Rhagoletis indifferens (Diptera: Tephritidae).
AB  - Sticky yellow rectangle traps have been used for many years to capture Rhagoletis
      (Diptera: Tephritidae) fruit flies. Traditional sticky yellow traps are coated
      with a sticky gel (SG) that can leave residues on the hands of users. An
      alternative to SG on traps are hot melt pressure sensitive adhesives (HMPSAs),
      which are less messy. The main objective here was to evaluate two rectangle traps
      of two yellow colors, the Alpha Scents Yellow Card coated with HMPSA (Alpha
      Scents, West Linn, OR), and the Pherocon AM trap coated with SG (Pherocon; Trece,
      Adair, OK), for capturing western cherry fruit fly, Rhagoletis indifferens
      Curran. Flies captured on both traps and held in the laboratory and field did not
      escape their surfaces. Flies caught on HMPSA were damaged when removed from traps
      without citrus solvent, whereas flies caught on SG could be removed intact
      without solvent. In field tests, Alpha Scents traps baited with an ammonium
      bicarbonate lure captured 1.4-2.2 times more R. indifferens than Pherocon traps
      baited with the same lure. Results of an experiment that eliminated differences
      in surface sticky material type, overall size, and surface sticky area between
      Alpha Scents and Pherocon traps suggested, although did not show conclusively,
      that more flies were caught on the Alpha Scents than Pherocon traps because of
      their different yellow color and/or lower fluorescence and not the HMPSA.
      Overall, the Alpha Scents trap is a viable alternative to the Pherocon trap for
      detecting R. indifferens.

PMID- 21735912
TI  - Patterns of mitochondrial haplotype diversity in the invasive pest Epiphyas
      postvittana (Lepidoptera: Tortricidae).
AB  - The light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera:
      Tortricidae), is a horticultural pest of Australia and New Zealand that has more
      recently invaded Hawaii, Europe, and California. A 2,216-bp region of the
      mitochondrial genome containing the cytochrome oxidase I and II genes was
      sequenced from 752 individuals. Haplotype network analyses revealed a major split
      between a predominantly Western Australian clade and all other samples,
      suggestive of either a deep genetic divergence or a cryptic species. Nucleotide
      and haplotype diversity were highest in the country of origin, Australia, and in
      New Zealand populations, with evidence of haplotype sharing between New Zealand
      and Tasmania. Nucleotide and haplotype diversity were higher in California than
      within the British Isles or Hawaii. From the total of 96 haplotypes, seven were
      found in California, of which four were private. Within California, there have
      been at least two introductions; based on genetic diversity we were unable to
      assign a likely source for a single moth found and eradicated in Los Angeles in
      2007; however, our data suggest it is unlikely that Hawaii and the British Isles
      are sources of the major E. postvittana population found throughout the rest of
      the state since 2006.

PMID- 21735913
TI  - Evaluation of mass trapping and mating disruption for managing Prionus
      californicus (Coleoptera: Cerambycidae) in hop production yards.
AB  - Larvae of Prionus californicus Motschulsky (Coleoptera: Cerambycidae) feed on the
      roots of many types of woody perennial crops and are serious pests of hop in the
      northwestern United States. The adult males are strongly attracted to a volatile
      sex pheromone, (3R,5S)-3,5-dimethyldodecanoic acid, that is produced by females.
      Here, we summarize the results of field experiments that evaluated the potential
      for using the synthetic pheromone (in a blend of all four possible stereoisomers)
      to manage infestations of P. californicus in commercial hop yards by mass
      trapping or mating disruption. Our research provides evidence that mass trapping
      may be effective in reducing mating success of the females: positioning surrogate
      females (sentinel traps baited with a low dose of pheromone) within a square of
      eight pheromone-baited traps resulted in an 88% reduction in the number of wild
      males that reached the sentinel traps compared with sentinel traps that were
      surrounded by traps baited with blank lures. Similarly, surrogate females that
      were surrounded by pheromone lures (without traps) were reached by 84% fewer wild
      males than surrogate females surrounded by blank lures, suggesting that mating
      disruption also may be effective. A mark-recapture experiment indicated that male
      P. californicus were attracted to traps baited with 1 mg of pheromone from as far
      away as 585 m. These studies indicate that 3,5-dimethyldodecanoic acid has very
      good potential for managing P. californicus in hop yards, and perhaps in other
      crops where it is a pest.

PMID- 21735914
TI  - Applications and mechanisms of wax-based semiochemical dispenser technology for
      disruption of grape root borer mating.
AB  - Grape root borer, Vitacea polistiformis (Harris) (Lepidoptera: Sesiidae), is an
      important pest of cultivated grapes (Vitis spp.) in the eastern United States
      from Michigan to Florida. There are few registered insecticides for control of
      this pest, and their efficacy is limited. Pheromone-based mating disruption is a
      potential alternative to insecticides for management of V. polistiformis. Wax
      based Specialized Pheromone & Lure Application Technology (SPLAT) was tested as a
      mating disruption method. Deployment densities of 150 dispensers per ha dosed
      with 5 mg of V. polistiformis pheromone were sufficient to achieve 95% mating
      disruption during a 7-wk trapping period. The disruption mechanism was determined
      to be competitive attraction. The release rate of pheromone from these dispensers
      was quantified to be approximately linear, 77.4 microg/g SPLAT/d. At this release
      rate, a minimum initial load of 5.4 mg of pheromone per dispenser would be needed
      to maintain disruption over a 9-10-wk V. polistiformis flight season,
      approximately 19 August to 21 October in central Florida. It should be noted,
      however, that the main pheromone component alone, (E,Z)-2,13-octadecadienyl
      acetate (ODDA), was effective (presumably by a noncompetitive mechanism) at
      higher loads per area of crop. Due to the cost of synthesis of highly pure
      isomers of the V. polistiformis pheromone components, mating disruption of V.
      polistiformis may be more practical with higher doses of commercially produced
      Zeuzera pyrina L. blend [95% (E,Z)-2,13-ODDA:5% (E,Z)-3,13-octadecadien-1-ol] or
      with (E,Z)-2,13-ODDA alone than with the V. polistiformis blend at lower rates.

PMID- 21735915
TI  - Population distribution and density of Pentalonia nigronervosa (Hemiptera:
      Aphididae) within banana mats: influence of plant age and height on sampling and
      management.
AB  - The banana aphid, Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae), is the
      most economically important pest of banana (Musa spp.) fields in Hawaii.
      Recently, there has been a concerted effort in Hawaii to learn more about the
      biology and ecology of this pest. However, limited work has been directed at
      determining the distribution of P. nigronervosa in banana fields and developing
      an integrated pest management plan. Therefore, a survey was conducted in banana
      fields throughout the Hawaiian Islands to determine the distribution and density
      of P. nigronervosa within banana mats from plants of different stages. Another
      aim was to determine whether the presence of ants on banana plants could be used
      as a reliable indicator of aphid infestations. Results of the survey showed that
      plants < or = 1.5 m (small sucker) in height contain the highest aphid
      populations per meter in plant height and that mother plants (> or = 2.5 m) had
      the lowest aphid counts and rate of infestation compared with small and
      intermediate suckers (> 1.5 < 2.5 m). More specifically, aphid population was
      reduced by approximately 12 aphids for every meter increase in plant height and
      that aphids are rarely found > or = 2.5 m within the plant canopy. Although there
      was an increase likelihood of finding ants on banana plants with higher aphid
      densities, results suggest that ants would be present on plants in the absence of
      aphids. Implications of these and other findings with respect to sampling and
      managing P. nigronervosa and associated Banana bunchy top virus are discussed.

PMID- 21735916
TI  - Impact of applying edible oils to silk channels on ear pests of sweet corn.
AB  - The impact of applying edible oils to corn silks on ear-feeding insects in sweet
      corn, Zea mays L., production was evaluated in 2006 and 2007. Six edible oils
      used in this experiment were canola, corn, olive, peanut, sesame, and soybean.
      Water and two commercial insecticidal oils (Neemix neem oil and nC21 Sunspray
      Ultrafine, a horticultural mineral oil) were used as the controls for the
      experiment. Six parameters evaluated in this experiment were corn earworm
      [Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae)] damage rating, the number of
      sap beetle [Carpophilus spp. (Coleoptera: Nitidulidae)] adults and larvae, the
      number of corn silk fly (or picture-winged fly) (Diptera: Ulidiidae) larvae,
      common smut [Ustilago maydis (D.C.) Corda] infection rate, and corn husk
      coverage. Among the two control treatments, neem oil reduced corn earworm damage
      at both pre- and postpollination applications in 2006, but not in 2007, whereas
      the mineral oil applied at postpollination treatments reduced corn earworm damage
      in both years. The mineral oil also reduced the number of sap beetle adults,
      whereas the neem oil applied at postpollination attracted the most sap beetle
      adults in 2007. Among the six edible oil treatments, the corn and sesame oils
      applied at postpollination reduced corn earworm damage only in 2007. The
      application of the peanut oil at postpollination attracted more sap beetle adults
      in 2006, and more sap beetle larvae in 2007. Olive and neem oils significantly
      reduced husk coverage compared with the water control in both years. The mineral
      oil application consistently increased smut infection rate in both 2006 and 2007.
      Ramifications of using oil treatments in ear pest management also are discussed.

PMID- 21735917
TI  - Hull split date and shell seal in relation to navel orangeworm (Lepidoptera:
      Pyralidae) infestation of almonds.
AB  - Hull split date, shell seal, and navel orangeworm, Amyelois transitella (Walker)
      (Lepidoptera: Pyralidae), infestation data for 19 varieties of almonds, Prunus
      dulcis (Mill.) D.A. Webb, were analyzed to determine the relationship of shell
      seal and hull split date on A. transitella infestation. Data for all varieties
      were collected from three University of California regional almond variety trials
      from 2003 to 2005, with a total of 8,550 nuts evaluated. A significant negative
      relationship was found between percentage of shell seal and percentage of navel
      orangeworm infestation, with lower percentage of shell seal correlating to higher
      percentage of infestation. Similarly, hull split date was negatively correlated
      with percentage of infestation, with later splitting varieties trending toward
      lower percentage of infestation. Although there are outlying varieties, hull
      split and shell seal are indeed significant components in varietal differences in
      almond navel orangeworm infestation. Understanding such factors gives insight
      into both the predictive value of almond characteristics related to navel
      orangeworm damage as well as other potential indicators.

PMID- 21735918
TI  - Impact of vineyard pesticides on a beneficial arthropod, Typhlodromus pyri
      (Acari: Phytoseiidae), in laboratory bioassays.
AB  - Laboratory bioassays were conducted to evaluate the effects of six vineyard
      pesticides on Typhlodromus pyri Scheuten (Acari: Phytoseiidae), a key predator of
      the mite Calepitrimerus vitis Nalepa (Acari: Eriophyoidae), in Pacific coastal
      vineyards. Materials tested were whey powder, 25% boscalid + 13% pyraclostrobin
      (Pristine), 40% myclobutanil (Rally), micronized sulfur (92% WP), 75% ethylene
      bisdithiocarbamate (mancozeb; Manzate), and 91.2% paraffinic oil (JMS Stylet),
      all applied at three concentrations. Pesticide dilutions were directly sprayed
      onto T. pyri adult females and juveniles, and each treatment was assessed to
      determine effects on direct mortality and fecundity. Five of the six pesticides
      tested resulted in < 50% mortality to adult and juvenile T. pyri for all
      concentrations 7 d after treatment. Paraffinic oil treatments displayed direct
      mortality > 50% for adult and juvenile assays and resulted in significantly
      higher mortality. Sublethal effects were more pronounced than acute pesticide
      toxicity, particularly in juvenile mite bioassays. Significant decreases in
      fecundity were detected in the sulfur and mancozeb treatments compared with the
      control in juvenile tests. The relative percentage of fecundity reduction for
      juvenile mites was highest when applying mancozeb (> 70%), sulfur (> 25%), or
      myclobutanil (> 20%). Adult mites displayed the greatest reductions in fecundity
      from applications of paraffinic oil (> 20%) or mancozeb (> 15%) treatments.
      Boscalid (+ pyraclostrobin) and whey displayed the least effect on fecundity
      across all bioassays. These results can be used to develop management guidelines
      in vineyard pest management practices to help conserve and enhance predatory mite
      populations.

PMID- 21735919
TI  - Further spread of and domination by Bemisia tabaci (Hemiptera: Aleyrodidae)
      biotype Q on field crops in China.
AB  - The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae),
      causes severe crop losses to many crops. The worst of these losses are often
      associated with the invasion and establishment of biotypes B and Q of this pest.
      Previous research in 2007 showed that biotype Q occurred with other biotypes in
      most field populations in China. To determine the current status of the biotype
      composition in the field, an extensive survey covering mainly eastern parts of
      China was conducted in 2009. Using polymerase chain reaction primers specific for
      the mitochondrial cytochrome oxidase I of biotypes B and Q and gene sequencing,
      we determined the biotypes composition in 61 whitefly populations and their
      distribution across 19 provinces in China. Our research revealed that only
      biotypes B and Q have been found in the field in 2009 in China. Among them,
      biotype Q was dominant in 44 locations (100.0%) and biotype B was dominant in 17
      locations (100.0%). The current survey indicates that biotype Q has rapidly
      displaced biotype B in most locations in China.

PMID- 21735920
TI  - Scavenging by spiders (Araneae) and its relationship to pest management of the
      brown recluse spider.
AB  - Experiments reported in Sandidge (2003; Nature 426: 30) indicated that the brown
      recluse spider, Loxosceles reclusa Gertsch & Mulaik, preferred to scavenge dead
      prey over live prey and that the spiders were not detrimentally affected when fed
      insecticide-killed crickets. Extrapolations made in subsequent media coverage
      disseminating the results of this research made counter-intuitive statements that
      pesticide treatment in houses would increase brown recluse populations in homes.
      This information was presented as if the scavenging behavior was specialized in
      the brown recluse; however, it was more likely that this behavior has not been
      well studied in other species. To provide a comparison, the current laboratory
      study examined the likelihood of non-Loxosceles spiders to scavenge dead prey. Of
      100 non-Loxosceles spiders that were tested (from 11 families, 24 genera, and at
      least 29 species from a variety of spider hunting guilds), 99 scavenged dead
      crickets when offered in petri dishes. Some of the spiders were webspinners in
      which real-world scavenging of dead prey is virtually impossible, yet they
      scavenge when given the opportunity. Therefore, scavenging is a flexible
      opportunistic predatory behavior that is spread across a variety of taxa and is
      not a unique behavior in brown recluses. These findings are discussed in relation
      to pest management practices.

PMID- 21735921
TI  - Temporal changes in chlorantraniliprole and indoxacarb in four midwestern soils
      and bioefficacy against the eastern subterranean termite (Isoptera:
      Rhinotermitidae).
AB  - Temporal changes in indoxacarb and chlorantraniliprole were determined in four
      midwestern soils by simulating commercial field applications of termiticides.
      Indoxacarb (0.0625 and 0.125%) and chlorantraniliprole (0.05 and 0.10%) were
      applied to each soil type in a rotating cement mixer to ensure uniform
      distribution of active ingredient (AI). Temporal and spatial changes in
      termiticide concentrations were determined by sampling soil cores subdivided at
      different depths (0-20, 20-40, and 40-61 cm) at various intervals up to 705 d
      after application. Percentage loss of indoxacarb was initially greater (0-180 d)
      than losses after 180 d. The lowest indoxacarb extractable concentrations were
      detected in soils closest to the surface. Chlorantraniliprole losses with time
      from all soils were slower than indoxacarb, with no differences observed with
      soil type or depth. Bioefficacy was evaluated in laboratory glass tube bioassays
      that monitored the distance of termite penetration into treated soils and
      resulting eastern subterranean termite, Reticulitermes flavipes (Kollar)
      (Isoptera: Rhinotermitidae), worker mortality. Bioassay data revealed that R.
      flavipes termites were unable to completely penetrate 50 mm of indoxacarb- and
      chlorantraniliprole treated soils at 0 d after treatment; however, termites were
      not deterred from foraging in these soils indicating no repellency to these
      termiticides. Termites completely penetrated (50 mm) soils treated with
      indoxacarb (0.0625%) by 360 d and complete penetration occurred in all soils
      treated with indoxacarb (0.0625 and 0.125%) by 705 d. Termites were unable to
      completely penetrate chlorantraniliprole-treated soils at 705 d. Mortality of
      termite workers was high in all chlorantraniliprole-treated soils at all sampling
      intervals. These data confirm that vertical differences in termiticide
      persistence occur in various soils.

PMID- 21735922
TI  - Toxicity of seven termiticides on the formosan and eastern subterranean termites.
AB  - Using both topical application and substrate (sand) treatments the toxicities of
      seven new generation soil termiticides were evaluated to determine the LD50 and
      LC50 against two economically important subterranean termite species, eastern
      subterranean termite, Reticulitermes flavipes (Kollar), and Formosan subterranean
      termite, Coptotermes formosanus Shiraki. The lethal dose toxicity (LD50) rankings
      for R. flavipes from highest to lowest were: fipronil > bifenthrin >
      chlorantraniliprole > cyantraniliprole > imidacloprid > chlorfenapyr >
      indoxacarb; the rankings for C. formosanus were fipronil > imidacloprid >
      chlorantraniliprole > cyanthraniliprole> bifenthrin > chlorfenapyr > indoxacarb.
      The respective lethal concentration toxicity (LC50) rankings were fipronil >
      bifenthrin > chlorfenapyr > indoxacarb > cyantraniliprole > chlorantraniliprole >
      imidacloprid for R. flavipes; and fipronil > chlorfenapyr > bifenthrin
      >imidacloprid > cyantraniliprole > chlorantraniliprole > indoxacarb for C.
      formosanus. The study provides an opportunity to directly compare toxicity,
      action speed, and bioavailability among this group of newer generation soil
      termiticides.

PMID- 21735923
TI  - Areawide field study on effect of three chitin synthesis inhibitor baits on
      populations of Coptotermes formosanus and Reticulitermes flavipes (Isoptera:
      Rhinotermitidae).
AB  - Periodic sampling of 43 independent monitors, initially active with Formosan
      subterranean termite, Coptotermes formosanus Shiraki, or the eastern subterranean
      termite, Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae), was
      conducted to evaluate the effects of cellulose baits containing one of three
      chitin synthesis inhibitors (CSIs)-diflubenzuron, hexaflumuron, or chlorfluazuron
      on termite populations. Diflubenzuron at 0.1% active ingredient (AI, wt:wt) had
      no noticeable effect on termite populations. Chlorfluazuron (0.25% [AI])
      significantly reduced termite populations in approximately 3 yr. Chlorfluazuron
      used after > 2-yr diflubenzuron treatment significantly reduced termite
      populations within months. This suggests diflubenzuron exposure increased the
      termite's sensitivity to chlorfluazuron accelerating population collapse.
      Hexaflumuron (0.5% [AI]) also reduced termite populations in approximately 2 yr.
      The process of removing most detectable termite populations from the
      approximately 160,000-m2 campus of the Southern Regional Research Center, New
      Orleans, LA, with CSIs baits required approximately 3 yr. Adjustments in the
      specific bait formulations and application procedures might reduce time to
      suppression. Establishment of new independent termite populations provides a
      mechanism to minimize the effects of baits. Remedial control measures around and
      under structures should be considered when implementing an area wide management
      strategy.

PMID- 21735924
TI  - A new trap and lure for Drosophila melanogaster (Diptera: Drosophilidae).
AB  - We conducted a series of nine laboratory experiments testing the response of
      "vinegar flies," Drosophila melanogaster Meigen (Diptera: Drosophilidae),
      released in bioassay chambers to experimental traps and lures. These experiments
      showed that an effective trap could be constructed from a clear 225-ml screw-cap
      jar fitted with a hollow 8-mm-diameter cylindrical cross bridge. Flies could
      enter the trap from either end of the cylindrical "gate" and in turn could enter
      the interior chamber of the trap through a cut out portion at mid-span of the
      cylinder. The experiments also showed that a natural-component lure could be made
      using a teabag containing freeze-dried banana powder, yeast, and carrageenan gum
      powder as a humectant. When dipped in water for 10-15 s and then placed in the
      bottom of a trap, the teabag provided effective attraction for at least 7 d.
      Captured flies were immobilized on a sticky card placed in the trap, allowing
      them to be easily seen. Unlike other traps that cannot be opened and have liquid
      lures, the cylindrical-gate trap can be reused repeatedly if the teabag and
      sticky card are replaced. A final two experiments showed that the prototype
      operational cylindrical-gate trap with a teabag lure captured 3.3 and 2.3 times
      more released flies, respectively, than the next best of three commercially
      available traps.

PMID- 21735925
TI  - Effect of seasonal changes in soil temperature and moisture on wood consumption
      and foraging activity of Formosan subterranean termite (Isoptera:
      Rhinotermitidae).
AB  - The objective of this study was to determine how seasonal changes affect the
      foraging activity and wood consumption of the Formosan subterranean termite,
      Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), in New Orleans, LA.
      There was a significant correlation between wood consumption and air temperature,
      soil temperature, and soil moisture, but not precipitation or number of rainy
      days. In the first year of the study, wood consumption was the lowest in
      December, February, and March. Wood consumption in January was not significantly
      different from consumption during the rest of the year. There were no seasonal
      changes in the number of underground monitoring stations occupied by termites. In
      the second year of the study, wood consumption was lowest from January to March.
      There was a significant decrease in the number of monitoring stations occupied by
      termites during the winter. This study determined that C. formosanus will remain
      in monitoring stations and resume feeding during warmer periods of a mild winter
      if average soil temperatures remain above 15 degrees C. Only prolonged periods of
      cold weather, with average soil temperatures below 15 degrees C, caused a
      significant number of termites to abandon underground monitoring stations.
      Seasonal changes in foraging activity would probably only disrupt baiting
      programs during severe winters in New Orleans, LA.

PMID- 21735926
TI  - Susceptibility of oriental fruit moth (Lepidoptera: Tortricidae) to two
      pyrethroids and a proposed diagnostic dose of esfenvalerate for field detection
      of resistance.
AB  - Laboratory colonies of oriental fruit moth, Grapholita molesta (Busck)
      (Lepidoptera: Tortricidae), were reared on 'Gala' apples (Malus pumila Mill.) and
      lima bean (Phaseolus lunatus L.) diet. Neonates were placed on wheat germ diet
      containing a range of concentrations of esfenvalerate or lambda-cyhalothrin;
      mortality was assessed after 96 h. For a long-term laboratory colony, LC50 values
      of esfenvalerate and lambda-cyhalothrin were 0.35 and 0.12 ppm, respectively, for
      progeny of insects reared on apples. For a colony established from Calhoun Co.,
      IL, in 2007, LC50 values of esfenvalerate and lambda-cyhalothrin were 0.37 and
      0.10 ppm, respectively, for progeny of insects reared on apples. LC50 values of
      these insecticides did not differ significantly for either colony when progeny of
      insects reared on lima bean diet were tested. We observed no consistent evidence
      of pyrethroid resistance in the Calhoun colony after laboratory culture for 21-23
      generations. We described the dose-response relationship for esfenvalerate
      applied topically in 1 microl of acetone to male moths from the long-term
      laboratory colony and estimated the LD99 to be 0.022 microg per moth. Application
      of 0.022 microg of esfenvalerate per moth to approximately 600 male moths from
      two putatively susceptible populations resulted in mean survivorship
      approximately equal to the expected level of 1.0%. Application of the same dose
      to 374 field-captured moths from two Calhoun Co. orchards with histories of
      pyrethroid use resulted in mean survivorship of 9.4 and 82%. We propose that
      0.022 microg of esfenvalerate in 1 microl of acetone can be used as a diagnostic
      dose for monitoring pyrethroid resistance in oriental ruit moth in the field.

PMID- 21735927
TI  - Selection for Cry3Bb1 resistance in a genetically diverse population of
      nondiapausing western corn rootworm (Coleoptera: Chrysomelidae).
AB  - Five short-diapause laboratory lines of western corn rootworm, Diabrotica
      virgifera virgifera LeConte (Coleoptera: Chrysomelidae), were selected for
      resistance to MON863, a variety of corn genetically modified with the Bacillus
      thuringiensis Berliner (Bt) transgene that expresses the Cry3Bb1 delta-endotoxin.
      Three of the selected lines were developed by incremental increase in the
      duration of exposure to MON863 over 11 generations (moderate selected lines). Two
      selected lines were developed from a control group by constant exposure to MON863
      for at least 14 d posthatch over seven generations (intense selected lines). At
      the end of the experiment, survivorship, as measured by adult emergence, was
      approximately 4 times higher in each of the selected lines reared on MON863
      compared with control lines. Estimates of realized heritabilities (h2) were 0.16
      and 0.15 for the moderate and intense selected lines, respectively, and are
      consistent with h2 estimates reported previously from a variety of pest insects.
      These lines provide data necessary for evaluating the potential for Bt resistance
      within diabroticite beetles and will be useful for developing improved insect
      resistance management strategies.

PMID- 21735928
TI  - Selection for resistance to mCry3A-expressing transgenic corn in western corn
      rootworm.
AB  - To investigate the development of resistance to mCry3A, a laboratory colony of
      the western corn rootworm, Diabrotica virgifera virgifera LeConte, was
      established from field survivors of mCry3A-expressing (MIR604) corn, Zea mays L.
      Feral adults emerging from MIR604 (selected) and isoline (control) field plots
      were collected and returned to the laboratory. Progeny of each colony was reared
      one generation on isoline corn and then crossed reciprocally with a nondiapausing
      colony. The resulting nondiapausing progeny were then reared on greenhouse corn
      in accordance with the wild type parent's origin (on MIR604 or isoline corn).
      After four, seven, and 10 total generations of selection, the resistance ratio of
      the selected colony was 0.5, 4.3, and 15.4 in terms of lethal concentration
      (LC)50 values in toxicity assays, with the latter two LC50 values being
      significant. After seven generations of selection in total, selected and control
      colonies were screened on MIR604 and isoline corn under field conditions. There
      was a significant colony x corn pedigree interaction in terms of plant damage.
      There was no significant difference in damage between MIR604 and isoline corn,
      whereas this difference was significant for the control colony. After 14
      generations of selection, a seedling bioassay was performed. Again, there was a
      significant colony x corn pedigree interaction, this time in terms of the number
      of larvae recovered. There was no significant difference in the number of larvae
      recovered from MIR604 and isoline corn for the selected colony, whereas this
      difference was significant for the control colony, although larval size was
      greater on isoline corn for both colonies. Resistance has developed in western
      corn rootworm laboratory colonies to all Bt proteins currently registered for
      corn rootworm management, which emphasizes the importance of adhering to
      resistance management plans for maintaining product efficacy.

PMID- 21735929
TI  - A reproductive fitness cost associated with Hessian fly (Diptera: Cecidomyiidae)
      virulence to wheat's H gene-mediated resistance.
AB  - We studied whether adaptation of the Hessian fly, Mayetiola destructor (Say)
      (Diptera: Cecidomyiidae), to plant resistance incurs fitness costs. In this gene
      for-gene interaction, adaptation to a single H resistance gene occurs via loss of
      a single effector encoded by an Avirulence gene. By losing the effector, the
      adapted larva now survives on the H gene plant, presumably because it evades the
      plant's H gene-mediated surveillance system. The problem is the Hessian fly larva
      needs its effectors for colonization. Thus, for adapted individuals, there may be
      a cost for losing the effector, with this then creating a trade-off between
      surviving on H-resistant plants and growing on plants that lack H genes. In two
      different tests, we used wheat lacking H genes to compare the survival and growth
      of a nonadapted strain to two H-adapted strains. The two adapted strains differed
      in that one had been selected for adaptation to H9, whereas the other strain had
      been selected for adaptation to H13. Tests showed that two H-adapted strains were
      similar to the nonadapted strain in egg-to-adult survival but that they differed
      in producing adults with smaller wings. By using known relationships between wing
      length and reproductive potential, we found that losses in wing length
      underestimate losses in reproductive potential. For example, H9- and H13-adapted
      females had 9 and 3% wing losses, respectively, but they were estimated to have
      32 and 12% losses in egg production. Fitness costs of adaptation will be
      investigated further via selection experiments comparing Avirulence allele
      frequencies for Hessian fly populations exposed or not exposed to H genes.

PMID- 21735930
TI  - Microsatellite markers reveal population structure and low gene flow among
      collections of Bactrocera cucurbitae (Diptera: Tephritidae) in Asia.
AB  - The melon fruit fly, Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae),
      is widespread agricultural pest, and it is known to have the potential to
      establish invasive populations in various tropical and subtropical areas. Despite
      the economic risk associated with a putative stable presence of this fly, the
      population genetics of this pest have remained relatively unexplored in Asia, the
      main area for distribution of this pest. The goals for this study were to employ
      nuclear markers to examine geographic collections for population genetic
      structure and quantify the extent of gene flow within these Southeast Asian and
      Chinese populations. To achieve these goals, we used 12 polymorphic
      microsatellite markers. A low level of genetic diversity was found among
      collections from China and higher levels were seen in Southeast Asia collections.
      Three genetically distinct groups, Southeast Asia, southwest China, and southeast
      China, were recovered by Bayesian model-based clustering methods, the
      phylogenetic reconstruction and the principal coordinate analysis. The Mantel
      test clearly shows geographical distance contributed in the genetic structuring
      of B. cucurbitae's populations. No recent bottlenecks for any of the populations
      examined. The results of clustering, migration analyses, and Mantel test,
      strongly suggest that the regional structure observed may be due to geographical
      factors such as mountains, rivers, and islands. We found a high rate of migration
      in some sites from the southwest China region (cluster 1) and the southeast China
      region (cluster 2), suggesting that China-Guangdong-Guangzhou (GZ) may be the
      center of melon fruit fly in the southeast China region.

PMID- 21735931
TI  - Resistance level to an aphid potato pest varies between genotypes from the same
      Solanum accession.
AB  - Plant resistance to aphids can be improved by introgressing resistant traits from
      wild Solanum species into the potato germplasm. Breeding parents are commonly
      selected from the different accessions of each species. Accessions originate from
      several seeds collected in a restricted area and are conserved as seeds in
      genebanks. Genetic heterogeneity may be expected between genotypes from the same
      accession and could influence resistance level. Working with the potato aphid,
      Macrosiphum euphorbiae (Thomas), and the accession PI243340 of Solanum
      chomatophilum (Bitter), which has been previously rated as resistant to M.
      euphorbiae, we genetically identified and assessed the resistance level of
      genotypes within the accession. A combination of two multilplex polymerase chain
      reactions (PCRs) discriminated the 13 plant genotypes assessed. Survival of M.
      euphorbiae, measured using clip cages, varied significantly between five
      genotypes, randomly selected among the 13 previously assessed, but did not differ
      between same-genotype plants. Survival among genotypes ranged from 0 to > 60% 12
      d after adult molt, and the least resistant genotype exhibited survival close to
      the susceptible standard, Solanum tuberosum L. Our results support the use of PCR
      multiplex methods to assess genetic heterogeneity in wild Solanum, and suggest
      that within accession genetic heterogeneity is sufficient to influence resistance
      level to aphids. Fine screening at the genotype level is preferable when
      assessing resistance to aphids.

PMID- 21735932
TI  - Discovery of English grain aphid (Hemiptera: Aphididae) biotypes in China.
AB  - The English grain aphid, Sitobion avenae (F.) (Hemiptera: Aphididae), is an
      important pest insect of wheat, Triticum aestivum (L.), in China. Grain aphid
      biotypes are necessary to breed aphid-resistant wheat varieties; however, none
      have currently been identified. Here, we describe a method to identify grain
      aphid biotypes and survey the aphid biotype variation in the wheat growth area of
      China. Clones of S. avenae were collected from 11 locations in China and used to
      establish culture populations. These populations were then used to assess the
      resistance of 12 wheat varieties. Based on resistance responses, seven
      differential hosts were selected to identify the biotype of S. avenae: Amigo,
      'Fengchan No. 3', Zhong 4 wumang, JP1, L1, 885479-2, and 'Xiaobaidongmai'. S.
      avenae was ultimately classified into five biotypes: EGA I, EGA II, EGA III, EGA
      IV, and EGA V. These methods provide a mechanism to detect the variation and
      evolution of grain aphids in different wheat-growing locations and also allow for
      selection of appropriate aphid-resistant germplasm for wheat breeding of
      commercial wheat cultivars.

PMID- 21735933
TI  - Chemical composition and fumigant toxicity of the essential oils from 16 species
      of Eucalyptus against Haematobia irritans (Diptera: Muscidae) adults.
AB  - Oils extracted from various species of Eucalyptus (Eucalyptus badjensis Beuzev &
      Welch, Eucalyptus badjensis x Eucalyptus nitens, Eucalyptus benthamii variety
      dorrigoensis Maiden & Cambage, Eucalyptus botryoides Smith, Eucalyptus
      dalrympleana Maiden, Eucalyptus fastigata Deane & Maiden, Eucalyptus nobilis
      L.A.S. Johnson & K. D. Hill, Eucalyptus polybractea R. Baker, Eucalyptus radiata
      ssp. radiata Sieber ex Spreng, Eucalyptus resinifera Smith, Eucalyptus
      robertsonii Blakely, Eucalyptus rubida Deane & Maiden, Eucalyptus smithii R.
      Baker, Eucalyptus elata Dehnh, Eucalyptus fraxinoides Deane & Maiden, E. obliqua
      L'Her) were obtained by hydrodistillation. The chemical composition of essential
      oils was determined by gas chromatography coupled to mass spectrometry. Essential
      oils were mainly composed of 1,8-cineole, alpha-pinene, alpha-terpineol, 4
      terpineol, and p-cymene. Vapors from these essential oils and their major
      components were found to be toxic to Haematobia irritans (L.) (Diptera: Muscidae)
      adults. An aliquot of each oil was placed in a cylindrical test chamber, and the
      number of knocked down flies was recorded as a function of time. Knockdown time
      50% was then calculated. Results showed that essential oil of E. polybractea had
      the highest knockdown activity of 3.44 min. A correlation was observed between
      the content of 1,8-cineole in the Eucalyptus essential oils and the corresponding
      toxic effect.

PMID- 21735934
TI  - Evaluation of surveillance methods for monitoring house fly abundance and
      activity on large commercial dairy operations.
AB  - Relative house fly, Musca domestica L., activity at three large dairies in
      central California was monitored during the peak fly activity period from June to
      August 2005 by using spot cards, fly tapes, bait traps, and Alsynite traps.
      Counts for all monitoring methods were significantly related at two of three
      dairies; with spot card counts significantly related to fly tape counts recorded
      the same week, and both spot card counts and fly tape counts significantly
      related to bait trap counts 1-2 wk later. Mean fly counts differed significantly
      between dairies, but a significant interaction between dairies sampled and
      monitoring methods used demonstrates that between-dairy comparisons are unwise.
      Estimate precision was determined by the coefficient of variability (CV) (or
      SE/mean). Using a CV = 0.15 as a desired level of estimate precision and assuming
      an integrate pest management (IPM) action threshold near the peak house fly
      activity measured by each monitoring method, house fly monitoring at a large
      dairy would require 12 spot cards placed in midafternoon shaded fly resting sites
      near cattle or seven bait traps placed in open areas near cattle. Software
      (FlySpotter; http://ucanr.org/ sites/FlySpotter/download/) using computer vision
      technology was developed to count fly spots on a scanned image of a spot card to
      dramatically reduce time invested in monitoring house flies. Counts provided by
      the FlySpotter software were highly correlated to visual counts. The use of spot
      cards for monitoring house flies is recommended for dairy IPM programs.

PMID- 21735935
TI  - Solidifying agent and processing of blood used for the larval diet affect
      screwworm (Diptera: Calliphoridae) life-history parameters.
AB  - Spray-dried whole bovine blood and a sodium polyacrylate polymer gel as a bulking
      and solidifying agent are among the constituents of the current larval diet for
      mass rearing screwworm, Cochliomyia hominivorax (Coquerel) (Diptera:
      Calliphoridae). Locally available, inexpensive dietary materials could reduce
      rearing cost and address an uncertain commercial supply of spray-dried blood. We
      compared efficacy of diet prepared from fresh bovine blood after decoagulation
      with sodium citrate or ethylenediaminetetraacetic acid (EDTA) or after mechanical
      defibrination, with the diet containing spray-dried blood using either gel or
      cellulose fiber as the bulking and solidifying agent. Several life-history
      parameters were compared among insects reared on each of the blood and bulking
      agent diets combination. Diets containing citrated blood yielded the lightest
      larval and pupal weights and fewest pupae. EDTA-treated blood with the gel also
      caused reductions. EDTA-treated blood with fiber yielded screwworms that were
      heavier and more numerous than those from the diet with citrated blood but
      lighter than those from the control diet using spray-dried blood. A reduction in
      percentage of adults emerging from pupae occurred from diets with both bulking
      agents using citrated blood and the diet using EDTA mixed with the gel bulking
      agent. As a group, the cellulose-fiber diets performed better than the gel diets.
      Larval diet did not affect adult longevity, weight of the eggs deposited by the
      females that emerged or subsequent egg hatch. Parameter measurements of insects
      from both defibrinated blood diets were similar to those from the spray-dried
      blood diets, indicating that fresh, defibrinated bovine blood can successfully
      replace the dry blood in the screwworm rearing medium.

PMID- 21735936
TI  - Seasonal abundance of stable flies and filth fly pupal parasitoids (Hymenoptera:
      Pteromalidae) at Florida equine facilities.
AB  - Beginning in November 2007 and continuing until December 2009, weekly stable fly,
      Stomoxys calcitrans (L.), surveillance was conducted at four equine facilities
      near Ocala, FL, by using alsynite sticky traps for adults and by searching
      immature developmental sites for pupae. Adult stable fly trap captures were
      highly variable throughout the year, ranging from 0 to 1,400 flies per trap per
      farm. The greatest adult stable fly activity was observed during the spring
      months of March and April, with weekly three-trap means of 121 and 136 flies per
      farm, respectively. The importance of cultural control measures was most apparent
      on the only farm with no reported insecticide use and the lowest stable fly trap
      captures, where an intense daily sanitation and composting program was conducted.
      A survey of on-site filth fly pupae revealed that 99.9% of all parasitoids
      recovered were Spalangia spp., consisting of Spalangia cameroni Perkins (56.5%),
      Spalangia nigroaenea Curtis (34.0%), Spalangia endius Walker (5.8%), and
      Spalangia nigra Latreille (3.7%). The implications of these findings are
      discussed.

PMID- 21735937
TI  - Extraction from soil of apterous Pemphigus populitransversus (Hemiptera:
      Pemphigidae) feeding on cruciferous vegetable roots.
AB  - The poplar petiolegall aphid, Pemphigus populitransversus Riley (Hemiptera:
      Pemphigidae), is a gall-forming aphid attacking leaf petioles of Populus spp.,
      its primary hosts. Its secondary hosts are the roots of cruciferous
      (Brassicaceae) plants, where it is also commonly known as the "cabbage root
      aphid." The apterous forms are destructive pests of cruciferous vegetables in
      many parts of the world. In our experiments, the root-feeding apterous forms were
      extracted from the soil using a Berlese funnel, which drives the aphids downward
      by using light and heat. The results show that a majority of apterous aphids
      (96.9%) were extracted from the soil in 2 h by using a 15-W light bulb in the
      Berlese funnels, whereas only 18.2% of aphids were extracted using a 25-W light
      bulb in a similar time period. The 25-W light bulb in the funnel generated too
      much heat (40-44 degrees C), which dried the soil too fast so that the aphids
      were unable to crawl downward to the collecting jars or killed the aphids
      directly. The advantages of using a Berlese funnel equipped with a 15-W light
      bulb as the light and heat source for sampling and extraction of the root feeding
      aphids include a uniform handling of each sample, less time spent, extraction of
      many samples at the same time, and storage of the aphids in containers for later
      counting in the laboratory. This technique seems to also be useful for extracting
      other mobile, small soil-dwelling arthropods.

PMID- 21735938
TI  - Sampling methods for assessing social wasps species diversity in a eucalyptus
      plantation.
AB  - Social wasps were collected in a eucalyptus (Eucalyptus urograndis, a genetically
      enhanced eucalyptus) plantation in Juiz de Fora, state of Minas Gerais,
      southwestern of Brazil, by using a variety of sampling methods, including active
      capture and baited traps set at two microhabitats. Six new records of social
      wasps for this region were obtained during the study: Brachygastra lecheguana
      Latreille, Polybia ignobilis Haliday, Polybia occidentalis Olivier, Polybia
      platycephala (Richards), Protonectarina sylveirae Saussure, and Protopolybia
      exigua Saussure (Hymenoptera: Vespidae). The active capture method sampled the
      greatest number of species. Baited traps installed in the canopy sampled agreater
      number of individuals of social wasps than those set on the trunks of eucalyptus
      trees. Fruit based baits captured a greater number of social wasp species than
      those baited with a protein derivative. Once no method was able to sample all
      species, we concluded that the efficiency of a survey can be maximized by using
      traps with a variety of different baits, in combination with active capture
      methods.

PMID- 21735939
TI  - Alcohol consumption and ethyl carbamate.

PMID- 21735940
TI  - Tuberculosis (TB) is an ancient illness caused by Mycobacterium tuberculosis.

PMID- 21735941
TI  - An improved record system for tracing outcome of "transferred-out" DOTS patients.
AB  - This study in Pakistan aimed to develop an improved record-keeping mechanism for
      the DOTS programme to establish the final treatment status of patients recorded
      as "transferred-out". In an intervention study in 40 DOTS diagnostics centres in
      Punjab province, a modification was made to the existing TB03 register. DOTS
      facilitators were trained to keep proper records of patients who transferred-out
      and transferred-in. Among 4442 registered cases, 104 patients (2.3%) transferred
      out of reporting centres. Correct matching of "-out and -in" patients was
      achieved for 74 (71.2%) patients; the remaining 30 (28.8%) were untraced. By
      tracing transferred-out cases, the adjusted outcome success rate increased in the
      intervention period from 89.6% to 90.9%.

PMID- 21735942
TI  - Hepatitis B vaccination coverage among Iranian children aged 15-26 months in
      2006.
AB  - This study in 2006 estimated the hepatitis B virus (BHV) vaccination coverage in
      the Islamic Republic of Iran at the national and district levels in urban, rural
      and remote populations of 41 university health service areas. Of 21 905 children
      recruited to the study, vaccination coverage based on vaccination card records
      was 100% in 14, 15 and 10 of the 41 university areas for the 1st, 2nd and 3rd
      doses of HBV respectively. National levels of HBV1, HBV2 and HBV3 coverage were
      98.9%, 98.8% and 98.4% respectively. The lowest HBV vaccination coverage rate was
      90.7% (in a remote district). HBV vaccination coverage was at an acceptable level
      in Iranian children.

PMID- 21735943
TI  - Integrated management of childhood illness in Lahej, Yemen: a qualitative
      analysis from the perspective of health providers.
AB  - Health providers' perceptions about the Integrated Management of Childhood
      Illness (IMCI) in Lahej governorate, Yemen, were explored in a qualitative
      analysis of 12 in-depth interviews in 2007. The following themes emerged:
      appreciation of clinical aspects of IMCI but unclear about community IMCI; IMCI
      working better in peripheral than central health facilities; inflexible rules;
      lack of integration of services; poor supervision; multiple roles for one person;
      success of immunization; basic equipment and drug supplies deficient; conflicting
      views about health committees and community participation; and solutions for
      community health problems. After 4 years of IMCI experience in Yemen, the gaps
      identified would endanger the positive influence of IMCI unless action is
      undertaken at different levels.

PMID- 21735944
TI  - Prevalence of overweight and obesity and associated risk factors in urban primary
      school children in Babol, Islamic Republic of Iran.
AB  - Childhood obesity is a major public health problem globally because of changes in
      lifestyles. We assessed the prevalence of overweight/obesity and associated
      factors in urban schoolchildren in Babol in a cross-sectional study of 1000
      schoolchildren aged 7-12 years. Weight and height were measured and data on
      sports activities and leisure time physical activities were collected by
      questionnaire. Overweight/obesity were assessed by comparing body mass index
      (BMI) values to the BMI index for age and sex percentiles set by CDC, Atlanta.
      The prevalence of obesity and overweight was 5-8% and 12.3% respectively. The
      prevalence was significantly lower in girls compared with boys (age-adjusted OR =
      0.69, 95% Cl: 0.50-0.96) and higher among private-school educated children
      compared with public-school educated students (age adjusted OR = 2.17, 95% Cl:
      1.47-3.18). For each additional score of leisure time physical activity, the age
      adjusted OR decreased significantly.

PMID- 21735945
TI  - Comparison of plaque removal efficacy of new and 3-month-old toothbrushes in
      children.
AB  - The cost of replacing toothbrushes at frequent intervals may be prohibitive in
      underdeveloped countries. The objective of this study in Tehran was to compare
      the plaque removal efficacy of new and 3-month-old toothbrushes in children. In a
      randomized, crossover study, 93 children aged 7-9 years old received a new manual
      toothbrush to use twice per day for 3 months. Plaque scores were measured using
      the modified Quigley-Hein plaque index after children had brushed for 60 seconds
      with either a new or their used toothbrush. Bristle wear of worn brushes was
      assessed by measuring brushing surface areas on digital images. Compared with new
      brushes in the same subjects, no statistically significant differences were found
      for plaque score reductions for 3-month-old toothbrushes exhibiting various
      degrees of wear. Worn toothbrushes are equally effective as new ones for
      children.

PMID- 21735946
TI  - Impact of an educational leaflet on parents' knowledge and awareness of
      children's orthodontic problems in Shiraz.
AB  - ABSTRACT Raising parents' awareness about dentofacial malocclusions is important
      for avoiding delays in seeking treatment. The aim of the present research was to
      assess the impact of an educational leaflet on parent's knowledge and awareness
      of orthodontic malocclusion in children. Parents of 533 7-9-year-old
      schoolchildren were randomized into a leaflet group who received an educational
      leaflet and a control group with no leaflet. Pre-and post-intervention test
      scores on a questionnaire about orthodontic problems were compared. Differences
      between post- and pre-test scores were significantly higher in the leaflet group
      than the control group for the total score and the domain on general awareness of
      orthodontic problems. Scores on the domain of knowledge of referral intervals did
      not differ significantly. Information leaflets may be useful for increasing
      parents' awareness of orthodontic problems in children.

PMID- 21735947
TI  - Physicians medication prescribing in primary care in Riyadh City, Saudi Arabia.
      Literature review, part 1: variations in drug prescribing.
AB  - Rational prescribing is associated with improved safety in drug use, better
      quality of life for patients and cost-effective care. Medication prescribing is a
      relatively unexplored area of research in Saudi Arabia and until now most studies
      have been in the secondary and tertiary health care system. This paper is the
      first of 3 review articles that form the background for a series of 5
      interconnected studies of prescribing patterns and medication errors in the
      public and private primary health care sectors of Saudi Arabia. A MEDLINE search
      was conducted to identify papers published in peer-reviewed journals over the
      previous 3 decades. The paper reviews variations in prescribing patterns and
      influences on physicians' prescribing behaviour worldwide and in Saudi Arabia.

PMID- 21735948
TI  - Physicians' medication prescribing in primary care in Riyadh City, Saudi Arabia.
      Literature review, part 2: rational prescribing.
AB  - Unlike sub-optimal prescribing, rational prescribing, coupled with certain
      indicators, is associated with improved safety in drug use in terms of selecting
      appropriate drug for prescribing, better quality of life for patients and cost
      effective care. Medication prescribing is a relatively unexplored area of
      research in Saudi Arabia and until now most studies have been in the secondary
      and tertiary health care system. This paper is the second of 3 review articles
      that form the background for a series of 5 interconnected studies of prescribing
      patterns and medication errors in the public and private primary health care
      sectors of Saudi Arabia. A MEDLINE search was conducted to identify papers
      published in peer-reviewed journals over the previous 3 decades. The paper
      reviews rational prescribing with its indicators, suboptimal prescribing,
      classification of medication errors, and how to achieve quality in health care
      prescribing worldwide and in Saudi Arabia.

PMID- 21735949
TI  - Physicians' medication prescribing in primary care . in Riyadh City, Saudi
      Arabia. Literature review, part 3: prescribing errors.
AB  - Medication errors are globally huge in magnitude and associated with high
      morbidity and mortality together with high costs and legal problems. Medication
      errors are caused by multiple factors related to health providers, consumers and
      health system, but most prescribing errors are preventable. This paper is the
      third of 3 review articles that form the background for a series of 5
      interconnected studies of prescribing patterns and medication errors in the
      public and private primary health care sectors of Saudi Arabia. A MEDLINE search
      was conducted to identify papers published in peer-reviewed journals over the
      previous 3 decades. The paper reviews the etiology, prevention strategies,
      reporting mechanisms and the myriad consequences of medication errors.

PMID- 21735950
TI  - [Medication prescribing pattern in primary care in Riyadh City, Saudi Arabia]
AB  - Physicians' prescribing behaviour is closely linked with patient safety and this
      area is poorly researched in Saudi Arabia. The objective of this study was to
      analyse physicians' prescribing patterns and the adequacy of noted information in
      the primary health care sector in Riyadh city. All medication prescriptions from
      5 public (n = 1182) and 5 private (n = 1200) health centres were collected by
      simple random sampling during 1 working day. Antibiotics were the most commonly
      prescribed drugs in both sectors. The mean number of drugs per prescription was
      2.08 and 2.36 in the public and private sectors respectively. Information and
      instructions noted on prescriptions varied considerably between private and
      public health centres. Similarly the medication prescribing pattern differed
      across the 2 health settings. Primary care physicians in Saudi Arabia need
      continuing training to improve their prescribing practices.

PMID- 21735951
TI  - Medication errors in primary care in Riyadh City, Saudi Arabia.
AB  - Medication errors can cause a variety of adverse drug events but are potentially
      preventable. This cross-sectional study analysed all medication prescriptions
      from 5 public and 5 private primary health care clinics in Riyadh city, collected
      by simple random sampling during 1 working day. Prescriptions for 2463 and 2836
      drugs from public and private clinics respectively were examined for errors,
      which were analysed using Neville et al.'s classification of prescription errors.
      Prescribing errors were found on 990/5299 (18.7%) prescriptions. Both type B and
      type C errors (major and minor nuisance) were more often associated with
      prescriptions from public than private clinics. Type D errors (trivial) were
      significantly more likely to occur with private health sector prescriptions. Type
      A errors (potentially serious) were rare (8/5299 drugs; 0.15%) and the rate did
      not differ significantly between the 2 health sectors. The development of
      preventive strategies for avoiding prescription errors is crucial.

PMID- 21735952
TI  - Determinants of physicians' medication prescribing behaviour in primary care in
      Riyadh City, Saudi Arabia.
AB  - This study in Saudi Arabia explored the determinants of physicians' prescribing
      behaviour in primary care in Riyadh city. A self-administered questionnaire
      designed to explore factors influencing prescribing (sociodemographic factors;
      practice setting; continuing education; access to educational materials;
      pharmaceutical company representatives; and patient factors) was completed by 87
      PHC physicians. A factor analysis of 56 variables extracted 7 factors that
      explained 46% of the variance. Of these, 4 components positively related to
      perceived good prescribing behaviour could be summarized as: clinical experience
      of physicians; use of educational materials for continuous updating of medical
      knowledge; enhanced levels of continuing medical education and willingness to
      involve patients in decision-making; and working as a team using pharmacists for
      consultation and emphasizing the role of medical education. The other 3 factors
      derived from the analysis were less easy to interpret and may have been
      statistical anomalies (or measurement errors).

PMID- 21735953
TI  - Predictors of quality of medication prescribing in primary care in Riyadh City,
      Saudi Arabia.
AB  - Identifying the indicators of good quality medication prescribing assists
      physicians in preventing medication errors. This study in Riyadh city aimed to
      examine the relationship between physicians' self-reported influences on
      prescribing and the quality of their prescribing, defined as the completeness and
      accuracy of their prescription documentation. A sample of 600 randomly selected
      prescriptions written by 87 physicians were rated as high or low quality. The
      same physicians completed a questionnaire to determine the indicators of quality
      prescribing. The 7 components identified with factor loadings +0.5 or -0.5 were
      subjected to binary logistic regression modelling. While a range of potential
      quality indicators of drug prescribing were identified, none of the variables
      underpinning the 7components/factors survived the binary logistic regression
      mode. More studies are needed that take into account other quality indicators of
      medication prescribing in Saudi Arabia.

PMID- 21735954
TI  - Effectiveness of three interventions on primary care physicians' medication
      prescribing in Riyadh City, Saudi Arabia.
AB  - A number of strategies have been shown to improve the quality of drug
      prescriptions. The objective of this study was to implement and assess the
      effectiveness of 3 interventions on physicians' prescribing and cost containment:
      training physicians about quality prescribing; regulatory and administrative
      measures to improve rational drug prescribing; and a multi-faceted approach using
      2 these strategies plus additional elements. Three public health centres, 1 for
      each intervention, were randomly selected; 61 physicians were trained in drug
      prescribing and completed a pre- and post-training questionnaire; and 100 post
      intervention prescriptions from each centre were compared. All 3 interventions
      effectively improved the quality of drug prescriptions and the notation of drug
      related information and trainees returned positive evaluations of the training
      course. Whether or not physicians' improvement in prescribing will be sustained
      is unclear and therefore subsequent follow-up evaluations are needed.

PMID- 21735955
TI  - Prevalence and correlates of tobacco use among grade 8-10 students in Peshawar,
      Pakistan.

PMID- 21735956
TI  - Measles remains a leading cause of death among young children.

PMID- 21735957
TI  - Epidemiology of measles outbreaks in Qatar in 2007.
AB  - While a major reduction in morbidity and mortality from measles has been achieved
      in Qatar since it adopted the measles elimination programme in 1997, the country
      has experienced small, recurrent measles outbreaks. The aim of this study was to
      determine the demographical and epidemiological characteristics of measles cases
      reported to the surveillance programme in Qatar in 2007. Of 362 confirmed cases
      67.7% were among children aged 1-14 years old and 16.9% were > 15 years. A
      majority of cases were unvaccinated (35.9%) or had unknown or undocumented
      vaccination status (47.0%). The high proportion of cases were among Pakistani
      nationals (39.5%) followed by Qataris (27.6%). Measles outbreaks were
      concentrated among the children of expatriates of Asian ethnicity with unknown
      vaccination status. This highlights the importance of achieving uniformly high
      levels of vaccination coverage in a community.

PMID- 21735958
TI  - Seroresponse to the second measles vaccine dose at school entry in Qassim
      province, Saudi Arabia.
AB  - In 2001, the measles immunization schedule in Saudi Arabia was changed to 2
      measles, mumps and rubella vaccine doses at 12 months and at 6 years. In this
      follow-up study we evaluated the seroresponse to the second measles dose before
      school entry. We recruited 138 children randomly from primary health care centres
      in Qassim; 124 children completed the study. Blood samples were collected before
      and 1 month after giving the second measles dose, before the age of 6 years.
      There was a statistically significant increase in the geometric mean titre of
      measles antibody, from 2205 m IU/mL before vaccination to 4723 mlU/mL after (P =
      0.0001). The proportion of children with positive ELISA results increased fro++
      94.2% before vaccination to 99.2% after (P = 0.02), while the proportion with
      protective level (> or = 200 mlU/mL) increased from 97.1% before vaccination to
      99.19% after (P = 0.21). The 2-dose measles immunization schedule can produce
      optimum protection at school entry if high vaccination coverage is guaranteed.

PMID- 21735959
TI  - Antenatal care in primary health care centres in Medina, Saudi Arabia, 2009: a
      cross-sectional study.
AB  - This study evaluated antenatal care (ANC) services for pregnant women attending
      primary health care centres in Medina city, Saudi Arabia in 2009. A cross
      sectional survey collected data on ANC tasks performed at visits by 394 pregnant
      women attending 7 clinics. ANC was assessed in 3 domains: clinical assessment (at
      the initial visit and return visit), health promotion and care provision. The
      mean duration of initial visits was 10.3 (SD 2.3) minutes and of return visits
      was 9.1 (SD 1.1) minutes. Overall performance on ANC tasks was fair. The
      significant predictors of ANC performance of tasks were: size of population
      served per centre; presence of more than 1 physician carrying out ANC at the
      centre; physician's age, mother tongue, nationality and qualifications; and
      woman's education and employment status. Having more physicians available for ANC
      in primary care centres could improve the standard of care.

PMID- 21735960
TI  - Beliefs and practices of Iranian pregnant mothers regarding vitamins and
      minerals.
AB  - The objective of this descriptive study was to examine the vitamin and mineral
      supplements safety beliefs and practices of Iranian pregnant women. Data were
      collected from 400 randomly chosen women. More than 50% of the participants
      believed that taking vitamins and minerals during pregnancy was safe; 87%
      reported taking iron during pregnancy, of which 71.7 % reported their doctor as
      the main recommender; 21.8% reported first trimester as the most beneficial time
      for iron supplementation, 13.0% second trimester and 3.0% third trimester.
      Although an appropriate intake of vitamins and minerals can assure health in
      pregnancy, excess can be harmful. Educational programmes for women of
      childbearing age are necessary.

PMID- 21735961
TI  - Anaemia prevalence and associated sociodemographic and dietary factors among
      Palestinian adolescents in the West Bank.
AB  - Anaemia still persists among children and women of childbearing age in Palestine.
      We investigated the prevalence of anaemia and associated factors among
      Palestinian school adolescents (aged 13-15 years) in Ramallah and Hebron
      governorates. Haemoglobin levels were measured to assess the prevalence of
      anaemia. The prevalence of anaemia was significantly higher in Hebron than in
      Ramallah among boys (22.5% versus 6.0% respectively), while among girls the
      figures were similar (9.2% and 9.3% respectively). Linear binomial regression
      analysis showed that among boys, anaemia was independently associated with
      residence in Hebron and higher standard of living, while among girls, anaemia was
      associated with higher father's education. Consumption of iron-rich foods, as
      recorded in food frequency questionnaires, had no significant effects on anaemia
      prevalence in both boys and girls.

PMID- 21735962
TI  - Diet, nutritional status and school performance among adolescents in Gaza Strip.
AB  - The associations between dietary intake, nutritional status and school
      performance among 932 adolescents aged 12-15 years were examined in a cross
      sectional survey in 2002 in north Gaza Strip. School performance was obtained
      from school records and height and weight were measured for body mass index
      (BMI). Self-administered questionnaires included sociodemographic characteristics
      and food frequency intakes. Adolescents consuming fruit and vegetables more than
      3 times per week were more likely to have good school performance (72.6% versus
      59.9%). When adjusting for sociodemographic variables and BMI, fruit and
      vegetables intake was positively associated with school performance (OR = 1.61,
      95% CI: 1.11-2.32) and stunting was negatively associated (OR = 0.53, 95% CI:
      0.31-0.90). The findings support a broader implementation of school nutrition
      programmes.

PMID- 21735963
TI  - Pattern of obesity and associated diabetes in Lebanese adolescents: a pilot
      study.
AB  - Obesity-associated diabetes in adolescents is increasing throughout the world. In
      this study, body mass index and capillary blood glucose were measured in a
      randomly selected sample of adolescents from 3 Lebanese private schools. Obesity
      was evaluated according to International Obesity Task Force cut-offs. Out of 300
      students, 18.7% were at risk of obesity and 3.0% were obese. Random glycaemia
      level was > or = 140 mg/dL in 10.3% of students. In those fasting, 10.5% had
      glucose intolerance and 3.5% had diabetes. Glucose levels were significantly
      higher in overweight versus normal weight individuals: 86 (SD 13) versus 96 (SD
      16) mg/dL. Among the normal weight group 8.6% had abnormal glycaemia while among
      those who were overweight 37.0% had abnormal glycaemia. Lebanese school students
      have high rates of overweight and of obesity-associated diabetes and glucose
      intolerance.

PMID- 21735964
TI  - Parametric modelling of survival following HIV and AIDS in the era of highly
      active antiretroviral therapy: data from Australia.
AB  - Parametric survival models have not previously been applied to survival following
      a diagnosis of HIV/AIDS in Australia. Four different parametric models-
      exponential, Weibull, log-normal and log-logistic--were applied to data both on
      HIV-positive cases and on cases diagnosed with AIDS collected through the
      national HIV/AIDS surveillance system. Using likelihood based goodness-of-fit
      criteria the Weibull model was found to be the best-fitted model for predicting
      survival following a diagnosis of HIV infection without and with a diagnosis of
      AIDS. Several covariates-age, sex, combined HIV exposure category, CD4 cell
      counts, antiretroviral treatment and AIDS-defining illnesses--were included in
      the parametric model to predict factors associated with future mortality.
      Predicted deaths were in agreement with the observed deaths following HIV
      infection and AIDS. The Weibull model will be applied for future projections of
      deaths from HIV/AIDS.

PMID- 21735965
TI  - Prevalence of hepatitis B surface antigen and hepatitis C virus antibodies among
      blood donors in Alexandria, Egypt.
AB  - Hepatitis B and C virus infections are common serious complications of blood
      transfusion. Over 6-month period in 2007/08 all samples from a blood bank in
      Alexandria, Egypt (n = 3420) were tested for hepatitis B surface antigen (HBsAg)
      and anti-hepatitis C virus (HCV) antibodies. A total of 119 donors (3.5%) were
      positive for anti-HCV and 47 (1.4%) for HBsAg. The mean age of HCV-positive
      donors was significantly higher than HBV-positive donors: 35.7 (SD 8.3) versus
      29.9 (SD 7.4) years. HCV and HBV prevalence was highest among males (93.3% and
      93.6% respectively), in urban areas (66.4% and 80.9%) and among manual workers
      (64.7% and 46.8%). The rates were lower than previous studies in Egypt, perhaps
      due to predonation screening which excludes those known to be at high risk of
      contracting bloodborne infections or who had other contraindications to blood
      donation.

PMID- 21735966
TI  - Oral health of Iranian children in 2004: a national pathfinder survey of dental
      caries and treatment needs.
AB  - A second nationwide survey in 2004 aimed to describe the oral health status of
      children in the Islamic Republic of Iran and to provide baseline data for the
      organization and evaluation of the national oral health promotion programme. WHO
      pathfinder sampling procedures were used to select representative samples of
      children aged 3, 6, 9 and 12 years. Data on decayed/missing/filled teeth, caries
      free rates and treatment needs were collected from 18 946 chiIdren using WHO
      standard methods. The mean dmft/DMFT indices were 1.9/- for 3-year-olds, 5.0/0.2
      for 6-year-olds, 3.6/0.9 for 9-year-olds and 0.6/1.9 for 12-year-olds.
      Significant differences in dental caries prevalence were found according to sex,
      province, urban/rural residence, family income and parents' level of education.

PMID- 21735967
TI  - [Schistosomiasis in Morocco: from discovery to after elimination].
AB  - This paper outlines the history of schistosomiasis in Morocco and the efforts
      made to eliminate it from the country. Since it was first diagnosed in 1914 in
      Marrakesh, schistosomiasis remained for decades a public health problem in
      Morocco. A national control programme was launched in 1982 and it led to a
      considerable reduction in the incidence and morbidity associated with the
      disease. Consequently, the programme shifted from disease control to an
      elimination process launched in 1994. This process aimed to eliminate the disease
      transmission by the end of 2004 and has helped to clear all known foci. Today,
      the challenge is to maintain schistosomiasis elimination and to be certified
      schistosomiasis-free by the World Health Organization.

PMID- 21735968
TI  - A long-term baby mix-up case in the Eastern Mediterranean region.

PMID- 21735969
TI  - National research for health system mapping in 5 countries in the Eastern
      Mediterranean region and perspectives on strengthening the systems.

PMID- 21735970
TI  - Analgesia in implant dentistry.
AB  - This month's feature article offers a review of analgesics commonly used in
      implant dentistry. While the placement of an implant is certainly of the utmost
      importance to the practitioner, ensuring adequate pain control during and after
      the procedure is one of the more important aspects to the patient. Selecting the
      most effective and appropriate agent to control swelling, pain, and anxiety
      requires a broad knowledge of these classes of medication.

PMID- 21735971
TI  - Dental tourism.

PMID- 21735972
TI  - No more fillings? Nanotechnology in practice.

PMID- 21735973
TI  - [Dioxins and food safety].
AB  - Among numerous potential chemical food contaminants, polychlorinated dibenzo-p
      dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls, collectively
      referred as dioxins, are commonly considered as bearing substantial risk for
      human health due to their toxicological properties, persistency and ability to
      bioaccumulate in food chains. The results of epidemiological studies suggest that
      environmental exposure to these compounds may affect multiple physiological
      processes in humans, mainly by the mechanism of endocrine disruption. Adverse
      health effects linked to the long-term exposure to dioxins include the increase
      of cancer risk, reproductive and developmental impairment as well as effects on
      immune functions. Exposure through food (mainly of animal origin) is the major
      source of dioxin exposure for humans, estimated to account for about 95% of the
      total intake for non-occupationally exposed persons. Recent studies showed that a
      consistent part of the European population has an intake exceeding
      internationally agreed "safe" doses as the Tolerable Daily or Weekly Intake (TDI,
      TWI). It is worthy to note that percentage of persons with estimated dioxin
      intake above tolerable limits is much higher among children than in adults. Since
      the "Belgian dioxin crisis" that occurred in 1999, the estimation of human
      exposure to these compounds and related consumer risk assessment has been
      recognized in the European Union as one of the priority activities in the field
      of food safety. Among activities undertaken by the European Commission during
      implementation of the Community Strategy for dioxins, furans and polychlorinated
      biphenyls the maximum and action levels have been established with random
      monitoring by Member States. The legislation on the requirements for sampling and
      methods of analysis used in the official control laboratories has been set up as
      well. Member States are obliged to measure background levels of dioxins and
      dioxin-like PCBs in defined food categories for the EU monitoring program on a
      yearly basis and to forward the results to the European Commission (since 2008 to
      the European Food Safety Authority). The monitoring results, covering samples
      collected from 1999 to 2008, evaluated and reported recently by EFSA, became the
      basis for updating maximum levels of dioxins and dl-PCBs as set up in Commission
      Regulation (EC) 1881/2006. The legislation will also be changed by replacing the
      current toxicity equivalency factors (TEFs) system from 1998 (WHO,1998-TEFs) by a
      new TEFs proposed by the WHO in 2005 (WHO 2005-TEFs). It is expected that new
      limits for dioxins and dl-PCBs in food will come into force not later than in the
      beginning of 2012.

PMID- 21735974
TI  - [Natural radioactivity of potassium 40K in curative and natural mineral waters
      and dose estimation].
AB  - Natural mineral and curative waters often characterize elevated level of mineral
      components. If the mineralization grows, the concentration natural radionuclides,
      which are one population's exposure sources on ionizing radiation, also grows.
      The main purposes work were: (1) determine the concentration isotope potassium
      40K in samples of water, (2) calculate effective doses caused by intake of water
      with potassium 40K, (3)- explore correlation between potassium 40K concentration
      and total dissolved solids (TDS). The concentration radioisotope 40K in analysed
      samples determined by means of gamma spectrometry. Received concentrations have
      values from the interval 0.65 to 28.42 Bq/dm3. Measured values compared to values
      calculated from physico-chemical analyses composition of water, which amounted
      from 0.07 to 22.87 Bq/dm3. The calculated effective dose resulting from intake
      water with potassium 40K, concentration 2.26 Bq/dm3 equaled 294 nSv by treatment
      and caused by inhalation water with concentration 40K 1.45 Bq/dm3 reached value 9
      nSv by treatment.

PMID- 21735975
TI  - [Determination of barium in natural curative waters by ICP-OES technique. Part I.
      Waters taken on the area of health resorts in Poland].
AB  - Maximum admissible concentration level (MACL) of barium in natural mineral
      waters, natural spring waters and potable waters was set at the level of 1 mg/l,
      while MACL of this element in natural curative waters intended for drinking
      therapies and inhalations were set at the levels of 1.0 mg/l and 10.0 mg/l,
      respectively. Those requirements were related to therapies which are applied
      longer than one month. Above mentioned maximum admissible concentration levels of
      barium in consumed waters were established after taking into account actual
      criteria of World Health Organization which determined the guidelines value for
      this element in water intended for human consumption at the level of 0.7 mg/l. In
      this work developed and validated method of determination of barium by
      inductively coupled plasma emission spectrometry technique was applied for
      determination of this element in 45 natural curative waters sampled from 24 spa
      districts situated on the area of Poland. Concentrations of barium determined
      were in the range from 0.0036 mg/l to 24.0 mg/l. Natural curative waters
      characterized by concentrations of barium in the ranges of 0.0036 - 0.073 mg/l,
      0.0036 - 1.31 mg/l and 0.0036 - 24.0 mg/l, were applied to drinking therapy,
      inhalations and balneotherapy, respectively (some of waters analyzed were
      simultaneously applied to drinking therapy, inhalations and balneotherapy). In
      the cases of 11 natural curative waters exceeding limit of 1 mg/l were observed,
      however they were classified mainly as waters applied to balneotherapy and in two
      cases to inhalation therapies (concentrations of barium - 1.08 mg/l and 1.31
      mg/l). The procedure of classification of curative waters for adequate therapies
      based among other things on barium concentrations meets requirements of the
      Decree of Minister of Health from 13 April 2006 on the range of studies
      indispensable for establishing medicinal properties of natural curative materials
      and curative properties of climate, criteria of their assessment and a specimen
      of certificate confirmed those properties.

PMID- 21735976
TI  - [The estimation of intake of selected and permissible preservatives used in food
      industry among people from Podlaskie voivodeship].
AB  - The work aimed at estimating intake of food containing permissible preservatives.
      The data was comprised of food samples from 14 poviats of Podlaskie voivodeship
      taken to detect presence of preservatives (sodium nitrate, nitrite, benzoic acid
      and its salt, sorbic acid and its salt). The samples were collected between 2004
      and 2007 by food inspection agency. Data concerning consumption of food provided
      results for an average consumption of some foodstuffs in households in which
      consumption of given foodstuff has been recorded by Polish Central Statistical
      Office, whereas data concerning consumption of soft drinks was provided by the
      report from March, 2008 (soft drinks market in Poland). It was stated that an
      average intake of the considered preservatives with an average diet is not a
      threat to people. Taking into account the fact data concerning consumption of
      foodstuffs in households is limited, it is advised to create databases comprising
      consumption of foodstuffs which would help in more precise evaluation of the
      intake.

PMID- 21735977
TI  - [Factors influencing on the Silesian University students' decisions concerning
      purchasing of vitamin and mineral food supplements].
AB  - Correctly composed diet covers the demands of a healthy adult for nutrients,
      vitamins and minerals. Nowadays constant increase of vitamin and mineral
      supplements of diet intake is observed. Customers have a great choice of diet
      supplements on Polish market. They are diversified under the quality and
      quantitative accounts. The main aim of this study was to evaluate main factors of
      Silesian University students' choice while they are purchasing particular diet
      supplements. The questionnaire survey was conducted in a group of 208 students at
      the age of 19 to 24. 99.5% of them admitted that they have supplemented their
      diets with vitamin and mineral preparations until the moment of the experiment.
      The results indicate that main factors that influence the students' decisions on
      purchasing these preparations are: composition of the supplement, price and
      convenient dosing regimen. Respondents indicate the internet as a main source of
      information on the supplements being discussed in the following study.

PMID- 21735978
TI  - [Appreciation of selenium concentration in blood and tissues of male rat as a
      result of diet ingredients changes and its supplementation with chosen group B
      vitamins].
AB  - The influence of diet ingredients and its supplementation with chosen B group
      vitamins on concentration of selenium in blood serum and tissues and activity of
      glutathione peroxidase in blood and liver of male rats was examined in the
      conducted experiment. The animals, aged 5 months, were divided into three groups
      and fed ad libitum with granulated mixes. Group I with basic mix containing among
      other things full grains, Group II with modified mix in which full grains were
      exchanged for wheat flour and in part with saccharose and Group III with modified
      mix supplemented in excess with vitamins B1, B2, B6 and PP. The experiment was
      conducted for six weeks during which the amount of consumed feeding stuff was
      calculated currently and once a week body mass of the animals was checked. When
      the experiment was finished the activity of GSH-Px was determined by
      spectrophotometric method in blood and liver whereas concentration of selenium in
      blood serum, muscles and in liver by fluorometric method. It was ascertained that
      the change of diet ingredients and its supplementation with chosen group B
      vitamins was in favour of lowering the amount of selenium in the examined
      tissues, and the decrease was not only the result of lower amount of the consumed
      element, but also of its increased usage, forced by the changes taking place
      under the influence of diet components and its supplementation.

PMID- 21735979
TI  - [Intakes of selected micronutrients by obese children and adolescents aged 7-13
      years before and after nutritional counselling].
AB  - The aim of this study was to analyze the intakes of selected micronutrients by
      obese children and adolescents aged 7-13 years before and after nutrition
      counselling. The study showed that the introduction of hypocaloric diet did not
      bring about any significant reductions in body weight of subjects expressed as
      body mass index BMI. Dietary counseling did not result in changes in the intakes
      of vitamin B12, folates, vitamin E, calcium, magnesium, potassium, which fell
      below the recommended values. The consumption of vitamin B6 vitamin C was in
      accordance with the recommended daily intake (RDI), but the intakes of sodium
      exceeded the RDI. In order to prevent the development of non-communicable
      diseases in adulthood, the diets of investigated subjects need to be improved.

PMID- 21735980
TI  - [Nutritional status and physical activity among citizens of Pomorze].
AB  - Physical activity constitute a key factor of healthy lifestyle. Physical activity
      decreases the risk of many chronic diseases--notably obesity, diabetes, coronary
      heart disease and cancer. It is recommended to be physically active at least 90
      min (3 days per 30 min) of vigorous activity or 150 min (5 days per 30 min) of
      moderate activity per week. The aim of the study was evaluation of physical
      activity level and indication of physical activity influence on BMI value. The
      obtained results indicate that 36.5% (40.4% of female "F" and 28% of male "M")
      did not perform any physical activity by way of sport. Moreover 36.5% (36.8% F
      and 32% M) performed sport activities 1-2 times per week and the average time of
      single activity of 73.9% (77.2% F and 64.0% M) was at least 30 min. It was also
      revealed that young citizens of Pomorze with correct BMI values were twice more
      active than young citizens of Pomorze with decreased or increased BMI values.

PMID- 21735981
TI  - [Nutritional habits of female students of the Medical University of Bialystok
      depending on the socioeconomic situation].
AB  - The aim of the study was the estimation of the selected nutritional habits of
      female students of the Medical University of Bialystok related to the socio
      economic situation of families (SES). The investigation included 251 female
      students (18% of a higher SES, 56.5% students of an average SES and 25.5%
      students of a lower SES). The highest percentage of female students consumed four
      meals a day independently on the socio-economic status. Lunch and afternoon snack
      were the most frequently omitted meals. The socio-economic situation of families
      did not differ significantly the consumption frequency of selected groups of food
      products among the studied students. The diets analysed in this study were
      characterized by low intake of whole meal bread, coarse-grained barley, milk and
      dairy products, fish, raw vegetables and fruit.

PMID- 21735982
TI  - [The influence of nutritional intervention on resting energy expenditure in obese
      adolescents aged 15-18 years].
AB  - The aim of this research was to assess the influence of dietary intervention on
      weight loss and resting energy expenditure (REE) in 20 obese and overweight
      adolescents (BMI = 29 +/- 3,8 kg/m2) aged 15-18 years. Nutritional habits and
      nutritional status were estimated before and after the introduction of low
      calorie diet. Measurements of REE were carried out by indirect calorimetry in a
      respiratory chamber Nutritional intervention had a significant influence in
      decreasing body weight (from 85 +/- 14.3 kg to 82.5 +/- 12.8 kg), BMI and fat
      mass. Muscle mass was found to be significantly elevated (p < 0.050). REE did not
      decline significantly due to nutritional intervention (p > 0.05; p = 0.84).

PMID- 21735983
TI  - [Level of knowledge on the hazards and ailments of menopause among women at pre
      menopausal age].
AB  - The aim of the project was to evaluate women's knowledge about symptoms, health
      hazards and preventive or mitigative measures against ailments of this life
      period. The study was conducted among 100 randomly chosen women, aged 42-49,
      experiencing the pre-menopausal time of life. The research tool was an anonymous
      questionnaire of own authorship. The results showed that it was menopausal
      symptoms the women were more familiar with rather than the health hazards
      resulting from hormonal deficiency. The surveyed indicated the following symptoms
      of this life period: mood fluctuations (82%), nervousness (74%), decreased
      elasticity of the skin (70%), hot flashes (69%), fatigue (66%), feeling unwell
      physically (65%), depressed mood (59%), tendency to cry (52%), sleep disturbances
      (50%). The women were not aware of the means to mitigate the disturbing symptoms
      of this time of life (with the exception of the hormone replacement therapy),
      having no knowledge on the role soya and soya-based supplements play in the
      alleviation of the nuisance of menopause.

PMID- 21735984
TI  - [Eating habits of a group of professional volleyball players].
AB  - The aim of the research was an analysis of the eating habits of professional
      volleyball players according to their sex and age. The research has been carried
      out on a group of 210 men players and women players at the age of 13-25,
      representatives of sports clubs in Ostroleka, Myslenice, Bydgoszcz and Warszawa.
      The research has revealed a limited realisation of rational diets by both men and
      women players. The most common mistakes made by them include a smaller number of
      meals during the day than recommended (especially among men), taking up training
      on empty stomach and insufficient frequency of consumption of dairy products,
      fish, vegetables and fruit. The research has also revealed excessive consumption
      of sweets, sweet sparkling drinks and fast food (mainly among men). The examined
      players to some extent only apply regular strategies of rehydration of their
      organisms. A high percentage of them do not pay attention to supplementation of
      liquids after an effort or they drink a lot of liquids at one time. The most
      frequently chosen drinks were mineral water and isotonic drinks. Supplementation
      was applied by a small percentage of the players, mainly men, who most often
      chose vitamins, Izostar, creatine, L-carnitine and HMB.

PMID- 21735985
TI  - [Assessment of risk factors of metabolic syndrome in girls and boys from south
      west area of Poland].
AB  - The research was aimed at evaluating risk factors: level of physical activity,
      BMI, using of unhealthy substances, appearing of illness in the family, age and
      sex in according to increase frequency of the metabolic syndrome (MS) in
      teenagers from Wroclaw. Height and the body weight were measured to assess BMI
      according to Cole's index in group of 409 girls and 369 boys. Metabolic syndrome
      was characterized when three of risk factors was noticed like: high level of
      triglycerids (> or = 110 mg/dl), glucose (> or = 110 mg/dl), waist circumference
      (> or = 90 percentyl) or low level of HDL - cholesterol (< or = 40 mg/dl).
      Logistic regression and odds ratio were used to identify number of group with MS
      (7.7% boys, 6.4% girls), generally 7.1%. One components of ZM was noticed in
      36.8% of group, two - 14.9%. Metabolic syndrome was not stated in 41.3% of
      teenagers. A significant influence of the excess weight and the obesity, the age
      of pupils, smoking cigarettes to the height of the risk of the metabolic syndrome
      and his components was stated. In the MS prevention they are essential alterable
      elements: a proper physical effort, the standardization of parameters of the body
      and not-taking substances.

PMID- 21735986
TI  - [Comparison of physical activity and favourite ways of spending free time in
      preschool girls and boys from the Mazowsze region].
AB  - The aim of this study was to compare physical activity of preschool girls and
      boys from the Mazowsze region and their favourite ways of spending free time. The
      studied population included 131 children aged 3 to 7 years. Parents filled in
      questionnaires about their children's physical activity and favourite ways of
      spending free time, as well as about general information on the children and
      their families. Gender had statistically significant influence on the children's
      birth weight, attending karate outside the preschool and on riding a bicycle,
      playing with a ball and playing with a dog as favourite ways of spending free
      time during sunny weather as well as playing on a computer and playing with dolls
      as favourite ways of spending free time during rainy weather. Gender had little
      influence on the studied preschoolers' physical activity. However favourite ways
      of spending free time turned out to be significantly different according to
      gender. Physical activity level in both girls and boys was low, similarly to
      their peers from the previous studies.

PMID- 21735987
TI  - [Health behaviours in children and youth based on perception own's proportions of
      body].
AB  - The aim of this work is analyse perceptions, intentions and actions related with
      own proportions of body conections with assessment to actual weight and height
      proportions (BMI) children and youth from Polkowice. Material examination
      includes measurement from research conducted in autumn of 2008 of Polkowice
      (Lower Silesia). Refine material includes measurement and survey 816 pupils (362
      boys and 454 girls) aged 10 - 15 of primary schools and secondary school. Body
      height and weight were measured and calculated on the basis of Body Mass Index
      (BMI). According to the international standards--cut off points for overweight
      and obesity by Cole et al. (2000). Estimate the frequency of overweight and
      obesity among the examined population. Some information about self-body
      proportions and activities undertaken to change them was obtained from a survey
      titled Youth Risk Behavior Survey (YRBS). The frequency of overweight among the
      examined population is more common by boys (17.7%) than by girls (12.8%). Obesity
      was observed among 4.7% of boys and 4.4% of girls. In the group of children and
      youth with overweight 42.2% boys and 67.2% girls correctly describes to actual
      weight and height proportions. Among the children and young people classified as
      overweight 88.9% boys and 75% girls perceived themselves as "too fat". Among the
      respondents with overweight and obesity 67.9% boys and 85.9% have declared trying
      to lose weight. The most popular methods used to regulating body weight are
      physical exercises and low-calories diet. Girls in comparing to boys they more
      often declare for lowering the body weight. The most popular method used to
      accomplish this aim is physical activity. One should explain to pupils of the
      appropriate body mass for the health and acquaint objective methods of estimation
      of the weight and height proportions and safe methods of their regulation.

PMID- 21735988
TI  - [Microbiological quality of hospital indoor air. Determinant factors for
      microbial concentration in air of operating theatres].
AB  - Foregoing research presents results of total number of bacteria and fungi assays
      carried out in air of operating theatres before, during and directly after
      planned surgical procedure. Basing on the results obtained in winter and summer
      the assessment of bacteria and fungi concentration in atmospheric air impact on
      microbial quality of air inside of operating theatre was elaborated.
      Investigation of the reason of high concentration of bacteria in air inside of
      operating rooms was conducted simultaneously. Presented results of microbial air
      purity collected from atmospheric air in parallel with indoor air demonstrated
      that air filters applied in air-conditioning system worked correctly and
      bacterial contamination of air had different reasons.

PMID- 21735989
TI  - [Elaboration of chemotaxonomical detection method of presence Legionella
      pneumophila cultures in water samples by GC-MS technique].
AB  - The aim of this study was elaboration of chemotaxonomical detection method of
      presence Legionella pneumophila cultures in water samples. In research, the
      profile of ester-linked fatty acids were specified, which are situated in the
      cell wall of the model bacteria cultures Legionella pneumophila 33152, which
      originate from ATCC collection Philadelphia 1 type. The profile were applied as a
      standard to detection L. pneumophila presence in water supply network. During the
      research, water samples were esterified and extracted and then specific taxonomic
      markers of this bacteria were indicated by gas chromatography coupled with mass
      spectrometry technique (GC-MS). The limit of detection were determined to 100
      jtk/100 ml water. Innovative chemotaxonomic method may be used in preliminary
      selection of water samples in routine analyses. Its application cuts down on time
      of analysis, by limitation on number of samples being diagnosed by classical
      microbiological methods.

PMID- 21735991
TI  - Public health nutrition concerns on consumption of red palm-oil (RPO): the
      scientific facts from literature.
AB  - There appears to be a state of uncertainty as far as the health benefits of
      consumption of Red Palm Oil (RPO) is concerned from public health point of view
      globally. Literatures are replete with conflicting information on saturated fatty
      acid content of palm-oil, with caution on the possibility of increasing low
      density lipoprotein (LDL) in the blood. The implication of this may be subsequent
      elevation of serum cholesterol when the oil is consumed. This review paper is
      aimed at providing scientific facts from well referenced journal articles on
      public health nutrition benefits of RPO. It considers findings from animal and
      human experiments, to arrive at conclusion based on scientific evidence on the
      potential health benefits associated with consumption of RPO. Although, the level
      of saturated fatty acids content may suggest health risk, the presence of
      carotenoids and other powerful anti-oxidants in RPO makes it one of the best
      cooking vegetable oils with health promoting properties.

PMID- 21735992
TI  - Prevalence and distribution of ocular onchocerciasis in three ecological zones in
      Nigeria.
AB  - The African Programme for Onchocerciasis Control (APOC) sponsored a baseline
      study in Nigeria between 1998 and 1999 on the prevalence and distribution of
      Onchocerciasis. The randomly selected 1,064 subjects in the baseline study
      underwent detailed eye examination in Cross River (rain forest), Taraba (savanna)
      and Kogi (forest-savanna) States. This paper compares and contrasts the public
      health significance of ocular onchocerciasis in these ecological zones. A
      blindness prevalence of 2.4% was recorded in the study, onchocerciasis being
      responsible for 30.2% of the bilaterally blind subjects. Onchocerciasis-induced
      blindness prevalence was relatively high in the rain forest and forest savanna
      zones of Cross River and Kogi States, Cross River having the highest site
      specific prevalence (50.0%), followed by Kogi (41.7%). Taraba recorded only
      27.3%. Other conditions identified included glaucoma, optic nerve disease and
      cataract rates of which were also found to be high among the population (6.9%,
      6.5 % and 8.9% respectively). Anterior segment onchocercal lesions, punctate and
      sclerosing keratitis were the predominant features of the infection in the
      savanna zone (14.1% and 6.3% respectively), while posterior segment lesions were
      much more common in the forest zone. The need to sustain the present efforts to
      control onchocerciasis through mass ivermectin treatment is recommended.

PMID- 21735993
TI  - Detection of viral RNA by RT-PCR from serum for molecular diagnosis of measles.
AB  - Measles continues to be a cause of morbidity and mortality in Cote d'Ivoire
      although the death rates are weak (2.4%). The monitoring and elimination
      programme of this disease require a laboratory confirmation testing by diverse
      methods of diagnosis needing diverse biological products. Serum is usually used
      for IgM detection. This study has therefore assessed the importance of the
      measles virus RNA detection from sera of measles suspected cases for confirmation
      of the case and determination of the genotype. A total of 45 sera tested were
      split into two groups according to the interval between the rash appearance and
      the day of blood collection: Group 1 (day 1 to day 3); group (2 day 4 to day 7).
      Four sera from Group 1 of the 45 (8.9 %) were positive by RT-PCR technique while
      10 (22.2%) sera were positive for IgM anti- measles virus by ELISA test. RT-PCR
      and ELISA showed the same performance in group 1 with a positivity rate of 13.79
      %. The B3 genotype was found. This result showed that the viral RNA can be
      detected in the serum but only from those sera collected the first 3 days after
      the rash appearance and could be used as palliative in case it is impossible to
      obtain other biological products.

PMID- 21735994
TI  - Strongyloidiasis: prevalence, risk factors, clinical and laboratory features
      among diarrhea patients in Ibadan Nigeria.
AB  - Strongyloidiasis is a parasitic infection caused by Strongyloides stercoralis.
      The infection is usually mild or asymptomatic in normal immunocompetent
      individuals, but could be very severe or even fatal due to hyper infection in
      individuals who are immunosuppressed. This study aimed at determining the
      prevalence, risk factors and features of strongyloidiasis among diarrhea patients
      in Ibadan. This is a descriptive cross-sectional study of diarrhea patients from
      a teaching hospital, three major government hospitals and one mission hospital in
      Ibadan. Self administered questionnaire, clinical assessment and laboratory
      investigations were used to confirm health status and presence of S. stercoralis.
      Diagnosis was made by microscopic examination of stool in saline preparation and
      formol-ether concentration. One thousand and ninety patients, (562 (51.6%) males
      and 528 (48.4%) females) consisting 380 (34.9%) children and 710 (65.1%) adults
      who had diarrhea were studied. The prevalence rate for the parasite among
      diarrhea patients was 3.0%. While the risk factor for infection remains contact
      with contaminated soil, malnutrition, steroid therapy, HIV/AIDS, lymphomas,
      tuberculosis, and chronic renal failure. Others are maleness, institutionalism
      and alcoholism. Predominant clinical presentations are abdominal pain, chronic
      diarrhea, and bloating and weight loss, Strongyloides stercoralis should be
      considered in diarrhea patients who are either malnourished or immunosuppressed.

PMID- 21735995
TI  - Prevalence of violence against pregnant women in Ibadan, Nigeria.
AB  - Women are at risk of violence at all stages of their life, including during
      pregnancy. Using a interviewer-administered questionnaire, 306 pregnant women
      were interviewed in two public secondary health facilities in Ibadan to compare
      prevalence and risk factors of VAW before and during pregnancy. Prevalence ofVAW
      a year before current pregnancy was 41.5% compared to 17.7% during pregnancy.
      Perpetrators before pregnancy were mostly relatives (22%), while during
      pregnancy, partners (64%). Major reasons for violence were "not obeying
      instructions" (33.3%) and "misbehaving" (26%). Education (OR 0.49; 95% CI 0.29
      0.83) and polygamous union (OR 9.56; 95% CI 3.71-24.63) and consumption of
      alcohol (OR 7.19; 95% CI 0.04-0.53) were statistically significant a year before
      pregnancy. Mothers occupation (OR 0.19; 95% CI 1.05-4.49); type of union
      (OR14.13; 95% CI 6.13-32.59), alcohol consumption by partner (OR 6.06; 95% CI
      0.05-0.54); and not wanting pregnancy (OR 3.53; 95% CI 1.20-9.30) were
      statistically significant in the index pregnancy. Hemorrhage (7.4% vs. 4.8%),
      abortion (1.9% vs. 1.2%), intrauterine death (3.7% vs. 1.2%) and premature labour
      (9.3% vs. 3.2%) were more often found in women who experienced VAW than those who
      did not, the latter was statistically significant (P < 0.05). Violence avoidance
      strategies included 'playing along' (51.3%) and 'praying' (21%). Pregnancy was
      protective against VAW. Empowerment of women through education and employment is
      crucial. Counselling on planning of families is also necessary. Screening for
      violence in pregnancy and close monitoring of the abused to ensure good obstetric
      outcome is recommended.

PMID- 21735996
TI  - Human immuno-deficiency virus and hepatitis B virus coinfection in pregnancy at
      the University College Hospital, Ibadan.
AB  - Human Immuno-deficiency virus (HIV) and Hepatitis B Virus (HBV) share common
      modes of transmission which include blood borne and the vertical routes.
      Although, the natural course of HIV does not appear altered by HBV, the rate of
      liver-related deaths is several times higher among HIV/HBV co-infected persons.
      Clinicians providing care for HIV positive individuals, including pregnant women,
      need to be aware of this problem. This is a 2-year cross-sectional study that
      commenced in January 2006, among HIV positive pregnant women seen at the
      University College Hospital, Ibadan. During the study period, 721 HIV positive
      pregnant women were screened for hepatitis B virus infection. Sixty-four women
      (8.9%) were positive for HBsAg, 14(1.9%) were HCV positive and 642 (89.2%) were
      negative for both HBV and HCV. One patient was positive forboth HBV and HCV.
      There were no remarkable differences between HIV infected and HIV-HBV coinfected
      patients in terms of the hematological, albumin and bilirubin measurements.
      Alanine transaminase was however higher in the HIV-HBV co-infected patients than
      HIV patients and this was statistically significant (17.5 iu/ ml vs. 15.0 iu/ml,
      p value--0.009). In addition, the CD4 cell count was lower and the viral load
      marginally higher in the hepatitis B virus positive patients. The differences
      were however not statistically significant (p value--0.114 and 0.644
      respectively). HIV-HBV co-infection in HIV positive pregnant women is not of
      negligible proportions as demonstrated in this study. Thus, HIV positive pregnant
      women should be screened for HBV and assisted to access care targeted at
      preventing morbidity and vertical transmission.

PMID- 21735997
TI  - Position paper for health authorities: archived clinical pathology data-treasure
      to revalue and appropriate.
AB  - Archived clinical pathology data (ACPD) is recognized as useful for research.
      Given our privileged de-identified ACPD from South West Pathology Service (SWPS),
      attempt is made to estimate what it would cost any researcher without such
      privilege to generate the same data. The Ethics Committee of the Area Health
      Service approved a request for Dr. Uba Nwose to use de-identified ACPD acquired
      by the SWPS for clinical laboratory-based translational biomedical science
      research. 10-years (1999-2008) have been pooled to constitute the database. Data
      include blood sugar, cholesterol, D-dime, ESR, glucose tolerance, haematocrit,
      HbA 1 c, homocysteine, serum creatinine, total protein and vitamins [C & E]
      amongst others. For this report, the bulk-billed-cost of tests were estimated
      based on number and unit price of each test performed. AU$ 17,507,136.85 is the
      cost paid by Medicare in the period. This amount is a conservative estimate that
      could be spent to generate such 10-years data in the absence of ACPD. The
      health/pathology service has not given any financial research grant. However, the
      support-in-kind is worth more than celebrated competitive research grants. It
      calls for revaluatrion by academic, research and scientific institutions the use
      ofACPD. For the countries where such provision is non-existent, this report
      provides a 'Position Paper' to present to the directorates or institutes of
      health authorities to appropriate the value of ACPD and approve of their use as a
      research treasure and resource management tool.

PMID- 21735998
TI  - Histopathological pattern of renal cell carcinoma in Ibadan.
AB  - There has been a paucity of Nigerian studies on renal cell carcinomas (RCC). This
      retrospective review analyzes cases of RCC diagnosed in the University College
      Hospital, Ibadan from January 1960 to June 2007. Cases were typed using the 2004
      World Health Organization classification of renal tumours. Papillary RCC were
      further grouped into Type 1 or 2 and Fuhrman's nuclear grade was determined for
      clear cell and papillary RCC. There were 159 cases, 108 being females, with a
      male to female ratio of 1:2.1. Peak age of occurrence was in the fourth decade.
      The right kidney was more commonly affected (58.6%). Papillary RCC was the most
      common variant accounting for 27 of the 62 cases that were available for review.
      Six (22.2%) of the 27 papillary RCC had the distinctive histological features
      that have been associated with Xp 11 translocation carcinoma. All 27 cases of
      papillary RCC were Type 2. Twenty-one (61.8%) RCC were Fuhrman's nuclear grade 1
      and 2. Renal cell carcinoma in Ibadan occurs two decades earlier than in
      Caucasians. Papillary RCC is the most common histological sub type of RCC in
      Ibadan, and Xp translocation carcinomas may be more common in this environment
      than earlier described in America. This is in contrast to the observation that
      clear cell carcinomas is the most common histological sub type of RCC in
      Caucasians series.

PMID- 21735999
TI  - Visual outcome of uveitic cataract in Ibadan.
AB  - The aim of this study is to evaluate the factors responsible for poor visual
      outcome in patients who had surgery for cataract due to uveitis in our
      subpopulation. A nonrandomized retrospective chart review of 28 patients (28
      eyes) diagnosed with uveitic cataract that had cataract surgery between June 2001
      and May 2007 at the University College Hospital, Ibadan, Nigeria was carried out.
      All had extracapsular cataract extraction with or without IOL implantation. The
      outcome measure was post-operative best corrected visual acuity. Over 60% of our
      patients achieved final best corrected visual acuity (BCVA) of 6/18 or better.
      The major causes of poor vision were posterior capsule opacity (PCO) in 6
      patients, cystoid macular oedema (CMO) in 2 patients and pre-existing
      chorioretinal scar in 1 patient. We conclude that post uveitic cataract surgery
      results in good visual outcome with few complications in Ibadan.

PMID- 21736000
TI  - The learning curve of radical hysterectomy for early cervical carcinoma.
AB  - Cervical cancer remains a public health concern in developing countries that lack
      the wherewithal to cope with the associated challenges. Screening for
      premalignant cervical lesions and offering definitive care for early disease is
      the key to preventing the scourge. We conducted an audit of the radical
      hysterectomies performed on account of early cervical carcinoma at our centre
      between September 2006 and August 2008, following capacity-building by Operation
      Stop Cervical Cancer. Ten women aged 35 to 60 years were managed. All had type
      III radical hysterectomy. Three patients had adjuvant teletherapy (one was stage
      IIb, diagnosed intra-operatively). There was a linear reduction in the surgical
      blood loss and duration of surgery. Average blood loss was 1500 mls; four had
      blood transfusions. One case was complicated with rectovaginal fistula (the woman
      with stage IIb disease) and another had bilateral lymphoedema and left lower limb
      sensory neuropathy. There was no tumour recurrence on follow-up. Definitive
      surgery for early cervical cancer is feasible in developing countries despite
      limited resources. Audit of surgical care of cervical cancer will assist in
      strengthening the scarce skill. Determination of suitable cases during
      preoperative evaluation is crucial to the success of the surgery.

PMID- 21736001
TI  - Progressing towards laboratory accreditation in developing countries.
AB  - Laboratory testing is of great value in the diagnosis and management of diseases.
      Good quality of results is essential if test results are to be meaningful.
      Uniformly high standards of laboratory practice are required to ensure that
      physicians may consistently rely on test results. Accreditation provides a way
      whereby a laboratory may meet international standards and provide assurance to a
      hospital's administration, medical and laboratory staff and patients that the
      laboratory is providing high quality results. In the absence of a national
      accreditation program, laboratories should undertake the low-cost or no cost
      actions that are elements of all accreditation programs. National societies
      concerned with the field of laboratory medicine or clinical pathology should work
      together with the appropriate government agencies to establish aNational
      Accrediting Body. Institution of an accrediting program will raise the visibility
      of clinical laboratory testing and ensure enhanced quality of testing for the
      entire population,

PMID- 21736002
TI  - [Collaboration between general practitioners and the school: survey about
      student's dietary habits in the first classes of secondary school in the province
      of Carbonia-Iglesias, Sardinia].
AB  - WHO stresses the importance of promoting balance diet among adolescents. The
      general practitioners are called at the forefront in the prevention of disorders
      related to eating habits. The present study describes a project to promote
      nutrition, created and run by general practitioners in the first classes of 20
      secondary schools in seven municipalities, in the province of Carbonia-Iglesias
      (Italy), for a sample of 509 students (220 females and 289 males). The results
      also offer an expanded view of the eating habits of adolescents. The results show
      that adolescents do not give importance to the breakfast that is often not
      complete or is not consumed, and only 50% of respondents drink milk. The highest
      percentage of students consuming the first and second course (45-59%) at lunch
      and dinner consumption of protein was high ranging between 64 and 80% for lunch
      and dinner at 63 and 66%. That is evidenced by these results can be a valuable
      aid for future health promotion interventions.

PMID- 21736003
TI  - Randomized, controlled nutrition education trial promotes a Mediterranean diet
      and improves anthropometric, dietary, and metabolic parameters in adults.
AB  - Several studies have shown that uptake of a Mediterranean diet could prevent many
      chronic diseases, such as cancer. However, the effectiveness of Mediterranean
      diet promotion interventions has not been well researched. The aim of this study
      was to evaluate the effectiveness of a nutrition education intervention for
      promoting the Mediterranean diet, by assessing changes in anthropometric,
      physical activity, dietetic and metabolic parameters in healthy adult subjects,
      before and after the intervention. Eighty participants, both sexes, aged 51-59
      years, were randomly assigned in a 1:1 ratio to the intervention or the control
      group. The intervention group participated in the Med-Food Anticancer Program
      (MFAP), designed to promote a Mediterranean diet. This was organized into 15
      weeks of intensive training and 10 weeks of consolidation. Participants of the
      two groups were assessed at baseline (T0) and after 25 weeks (T1) for
      anthropometric, physical activity, dietetic, and metabolic parameters. The
      hypothesis was that subjects participating in MFAP would show an improvement in
      these parameters. The primary endpoint was an improvement of the Mediterranean
      Adequacy Index (MAI), calculated by dividing the percentage of total energy from
      typical Mediterranean food groups by the percentage of total energy from non
      typical Mediterranean food groups. At T1, the intervention group showed a
      significant decrease in body weight (-8.3%, P = 0.045), body mass index (-12.4%,
      P = 0.05), cheese (53.0%, P < 0.0001) and meat (-49.3%, P = 0.005) intake,
      fasting glycaemia (-9.2%, P = 0.012), and fasting insulin (-32.6%, P = 0.014), C
      Reactive Protein (-34.0%, P = 0.005). They showed a significant increase in MAI
      (+213, P < 0.0001), physical activity (expressed in steps per day, +200.4%, P <
      0.0001), fruit (+38.8, P < 0.0001), vegetables (29.3%, P < 0.0001), and dietary
      fiber (+38.6%, P = 0.04) intake. In contrast, the control group presented non
      significant variations in measured parameters, for exception of cheese intake
      (+18.2%, P < 0.0001). The MFAP was found to promote uptake of the Mediterranean
      diet, and improve anthropometric, physical activity, dietary, and metabolic
      parameters in healthy subjects.

PMID- 21736004
TI  - [Comparison of the leukaemia incidence in two cohorts of farmers and traders in
      the Vercelli province of Italy, 2002-2009].
AB  - This study aims to investigate the incidence of leukaemia between 2002 and 2009
      (ICDIX 204-208) among farmers active in the Vercelli province (North West Italy),
      during the period: 1962-1991. The farmer cohort (14397 subjects, 78 cases) was
      compared with a retail trader cohort (4565 subjects, 11 cases) who were Vercelli
      province residents as well, but not exposed to the risk factors associated with
      professional farming. A proportional hazard Cox model shows among the farmers, an
      approximately double leukaemia incidence with respect to traders (Hazard Ratio =
      1,90 P-value 0,043 IC95% 1,00-3,60). Moreover men's incidence appears
      approximately to double that of women (Hazard Ratio = 1,92 P-value 0,003 IC95%
      1,25-2,95).

PMID- 21736005
TI  - [State of health of the population of Trino (Vercelli): cancer mortalities 2000
      2007 and historical analysis of all causes of death from 1980 to 2000].
AB  - The survey takes an in-depth look at the state of health of the inhabitants of
      Trino, in the province of Vercelli. The presence of various industries like
      cement factories, foundries and the placing of a nuclear plant (E.FERMI) in past
      decades, led to the carrying out of several surveys in order to reveal possible
      epidemiological excesses. In the survey in question, a detailed analysis of
      cancer mortalities occurring from 2000 to 2007 was carried out, examining the
      results in comparison with the Local Health Authorities of Vercelli and data from
      the Rencam Registry of the city of Turin from 2004 to 2006. The results highlight
      and confirm significant excesses for cancers like the nervous system, leukaemia,
      mesothelioma and peritoneum. Subsequent historical analysis (1980 - 2000) with
      data from the BDM Piedmont with regards to cancer mortalities confirms part of
      our data, while for all other causes we highlight the anomaly of amyotrophic
      lateral sclerosis in both sexes after the age of 65. The combination of these
      related results and our previous study of cases in Trino certainly require an in
      depth epidemiological analysis through etiological studies.

PMID- 21736006
TI  - [Healthy design for sustainable communities].
AB  - Health, quality of life and sustainable development are strongly interconnected.
      The quality of living is a complex concept that includes different meanings. The
      quality of life issue has been studied for a long time, even if its measurement
      is a more recent matter. It's possible to distinguish two main approaches: the
      first one, depending on which the quality of life corresponds to the social
      wellbeing and it can be measured objectively; the second one, that emphasizes the
      perceptive dimension of quality of life, such as needs, feelings and aspirations.
      According to the WHO's wide definition of wellbeing, this paper suggests an
      approach focused on the effects that urban planning and designing can have on the
      health of citizens. Actually many of the problems of the cities like pollution,
      inequity, lack of services and accessibility depends on decisions about the
      development of land and buildings. To have more attractive cities in the future
      it is important that professionals involved in planning and local authorities
      focus on the major determinants of health: the physical and social environment in
      which people live and the nature of their lifestyles. The experience explained in
      this paper shows as local authorities can support professionals in designing
      process, producing quick and effective benchmark in order to improve the quality
      of urban spaces and architecture. More in deep the tool works by a set of
      performance indicators developed with the purpose to assess the degree of
      sustainability of building and urban space proposals at the planning stage (and
      at later stages), against a range of criteria. This evaluation procedure can be
      considered as a common platform from which different stakeholders can agree goals
      and work together contributing to increase the benefits of a well-designed built
      environment.

PMID- 21736007
TI  - [Light wellbeing in hospital: research, development and indications].
AB  - Aim of the research is to form design indicators to guarantee light comfort in
      hospital environments for inpatients as well for workers. The research is
      articulated in different phases: drawing up, elaboration and distribution of a
      questionnaire to study indoor natural and artificial lighting, and effects on
      human being; architectural and lighting analyses of the investigated hospitals;
      elaboration -through graphics- of the questionnaire answers; drawing up of design
      indications for visual comfort in hospitals. These indications relates natural
      lighting, artificial lighting, indoor spaces and human being.

PMID- 21736008
TI  - Evaluation of the adherence to a new potassium chloride storage and handling
      hospital protocol: an observational study.
AB  - The study aim to deal with problem of manage potassium chloride concentrate
      solution after the introduction of a new protocol on correct use (storage and
      handling) of these drugs in a high specialization-teaching hospital. The study,
      conducted from January 2009 to March 2009, was divided in two part: observation
      of the compliance of concentrated electrolytes solutions storage in 14 wards and
      prospective observational study on the compliance to the new protocol in the
      steps of prescription, preparation and administration of these drugs. 49
      preparations and administrations of electrolytes solutions were observed. Medical
      prescriptions were made in a dedicated schedule in 40.8% (20/49), in therapy
      sheet in 36.7% (18/49), in 14.3% (7/49) the prescription was verbal and after
      written. Patient identified data was present in 85.7% of cases, solvent type in
      61.2%, prescription date in 69.4%, prescription hour in 10.2%, signature of
      prescriptor in 77.6%, administration speed in 57.1%, administration date in
      71.4%, administration hour in 32.7%. Data show a scarce knowledge of the protocol
      by the physicians or a difficulty in using an additional schedule respect to the
      existent. Lack of the prescriptor's signature was an important problem such as
      the absence of speed, date and hour of administration.

PMID- 21736009
TI  - Mutations in GDI1 and X-linked non-specific mental retardation.
AB  - Mental retardation (MR) is a complex phenotype characterized by suboptimal
      functioning of the central nervous system (CNS). It is estimated that from 1 to
      3% of the general population is affected with MR. MR or "intellectual disability"
      can be caused by genetic as well as environmental causes that act on the
      development and functioning of the CNS prenatally, perinatally or postnatally.
      Genetic causes of MR include chromosome aneusomies, chromosome structural
      abnormalities, genomic disorders and monogenic diseases. Amongst children, acute
      MR (QI < 50) is estimated at 0.4% and faint MR is about 2.5-3%. To determine the
      etiology of the MR, many diagnostic studies have been conducted and they show
      that MR is very heterogeneous and its etiology is not yet known in 20-50% of the
      group of patients with severe MR. This percentage increases up to 75-80% in the
      group of individuals with mild or "borderline" forms of MR. In light of the
      literature results, we tried to carry out a screening of 41 subjects with
      nonspecific MR for the detection of mutations in the gene GDI1 using the DHPLC
      methodology. This technique has the following advantages: low cost, high
      sensitivity (> 95%), and it can be done quickly. We have found 3 nucleotide (nt)
      substitutions: an intronic polymorphism at nt 107877 A --> C, a polymorphism in
      exon 3 at nt 109259 T --> C (Asn73Asn), and an intronic polymorphism at nt 110314
      G --> C. The mutations in this gene are common and do not seem to influence the
      gene expression so as to cause a change in phenotype. These results therefore do
      not encourage the research of a diagnostic protocol designed for mutational
      analysis of the GDI1 human gene as the only responsible factor for a complex
      disease as Mental Retardation X-linked (MRX).

PMID- 21736010
TI  - [Innovative materials in orthopaedics: the crosslinked polyethylene (XPE)].
AB  - More than 150.000 hip and knee arthroplasties are performed every year in Italy.
      More than 50% of the patients receive a polyethylene component (Ultra High
      Molecular Weight PolyEthylene, UHMWPE). Polyethylene abrasive wear induces over
      time in vivo a foreign-body response and consequently osteolysis, pain and need
      of implant revision. Furthermore, oxidative wear due to gamma-rays sterilization
      caused in the '90ies several and severe failures. To solve these problems, since
      then, the orthopaedics research has been addressed to: 1) develop new cross
      linked polyethylene with a higher molecular mass than UHMWPE and, consequently, a
      higher abrasive wear resistance; 2) avoid the oxidative wear induced by gamma
      rays sterilization, by using other sterilization methods and by stabilizing
      UHMWPE by means of antioxidants such as Vitamin E. According to the most recent
      studies, performed on limited cohorts and mostly funded by manufacturers, cross
      linked polyethylene shows a better abrasive wear resistance if compared to the
      conventional polyethylene but no significant differences have been detected in
      the clinical outcomes. Clinical follow up of Vitamin E stabilized PE are not yet
      available. The organization of national arthroplasties registries, able to trace
      and characterize the implanted devices and based on the whole patients
      population, will facilitate the early detection of devices that show a
      performance inferior than the expected one. In Italy, the National Institute of
      Health has been entrusted by the Ministry of Health to organize the national
      arthroplasty registry.

PMID- 21736011
TI  - ["Do you know your myocardial infarct risk?"].

PMID- 21736012
TI  - [Acute myocardial infarction: diagnosis and treatment].
AB  - Acute ST-elevation myocardial infarction (STEMI) represents a cardiac emergency
      with a high early mortality. Over the last decades, prognosis of patients with
      STEMI has dramatically improved. This has primarily been a result of advances in
      coronary interventional techniques as well as medical therapy. Direct
      percutaneous recanalization of the infarct-related artery represents the gold
      standard in treating STEMI, specifically when performed within two hours after
      first medical contact. These timelines imply logistical challenges for ambulance
      and hospital services. Furthermore, the broad variety of antithrombotic
      (acetylsalicylic acid, P2Y12 and GPIIb/IIIa receptor antagonists) and
      antithrombin medication (heparins, direct thrombin inhibitors) requires a sound
      understanding of the current evidence, guidelines and the individual patient
      characteristics to offer optimal medical therapy to the individual patient.

PMID- 21736013
TI  - [Zinc deficiency. Symptoms, causes, diagnosis and therapy].
AB  - Zinc is an essential trace element being required for numerous metabolic
      processes. The diagnosis of zinc deficiency is based on four main criteria,
      namely anamnesis, symptomatology, belonging to well-defined risk groups and the
      determination of biomarkers. The diagnosis of overt zinc deficiency is
      unproblematic in contrast to moderate states. The review presented here shall
      help to detect the latter ones. The pharmacotherapy of of zinc deficiency
      consists in oral administration of zinc salts.

PMID- 21736015
TI  - Global survey highlights concerns over poor working environments.

PMID- 21736014
TI  - [Cardiotoxicity of chemotherapy. An increasing problem in oncology and
      cardiology].

PMID- 21736016
TI  - Union calls for nurse ratios as staff say they struggle to cope.

PMID- 21736017
TI  - Nurse prescribers are popular with patients, ministers told.

PMID- 21736018
TI  - Carter attacks NHS over lack of proper training for support staff.

PMID- 21736019
TI  - Financial strain and deadlines leading to job losses and closures.

PMID- 21736020
TI  - Patients attack NHS reforms, but is Mr Cameron listening?

PMID- 21736021
TI  - Hero of cyclone Yasi.
AB  - Earlier this is year a midwife from the UK made the news when she delivered a
      baby in the middle of Queensland, Australia's, worst-ever cyclone.

PMID- 21736023
TI  - Innovation by example.
AB  - Real case studies of how nurses are improving patient care are now available to
      inspire others.

PMID- 21736022
TI  - Rapid response to crisis.
AB  - In the wake of the earthquake and tsunami, the Japanese Nursing Association
      mobilised 914 nurses specially trained in disaster work to help in the worst hit
      areas.

PMID- 21736024
TI  - Join the network.
AB  - The practical use of telehealth systems is considered in the follow-up to last
      week's article.

PMID- 21736025
TI  - Child sexual abuse: a new approach to professional education.
AB  - Child sexual abuse is a highly emotive subject and nurses have a key role to play
      in caring for survivors. Educating students about this role is difficult because
      a conventional classroom approach does not prepare students adequately or give
      them sufficient insight into the experiences of victims. The Stilwell virtual
      simulation model is a radical new approach which aims to assist learning by
      immersing students in a realistic multimedia simulation of a typical community.
      This model allows insightful learning about difficult areas such as child sexual
      abuse. Its use and contribution to learning in this area are discussed.

PMID- 21736026
TI  - Improving the quality of community placements for nursing students.
AB  - This article explores the development and implementation of a structured
      framework to enable adult branch nursing students to undertake delegated care
      activities independently while working in community practice placements and
      aligned to district nursing teams. A working group comprising academic staff from
      De Montfort University, Leicester, and practice colleagues from Leicestershire
      Partnership Trust collaborated to develop the framework and accompanying
      guidelines.

PMID- 21736027
TI  - Ectopic pregnancy: risk factors, diagnostic procedures and treatment.
AB  - This article provides an overview of ectopic pregnancy and describes the risk
      factors, diagnostic procedures and treatment options. In addition, the nurse's
      role in caring for and supporting women experiencing an ectopic pregnancy is
      discussed.

PMID- 21736028
TI  - Hepatitis C.

PMID- 21736029
TI  - Hit the ground running.

PMID- 21736030
TI  - Special service.

PMID- 21736031
TI  - Position of influence.

PMID- 21736032
TI  - Health care legislation: a challenging session.

PMID- 21736033
TI  - Nurses expanding education with simulators.

PMID- 21736034
TI  - The future of Nursing Campaign for Action in Colorado.

PMID- 21736036
TI  - Lessons in leadership.

PMID- 21736035
TI  - Political advocacy, anyone? Across the country, RNs participate in lobby days and
      other crucial actions.

PMID- 21736037
TI  - Reducing revolving door readmissions.

PMID- 21736038
TI  - CNPE discusses social networking, other issues.

PMID- 21736039
TI  - Texas Nurses Association promoting enhanced nurse protections.

PMID- 21736040
TI  - [A trial of 89Sr bremsstrahlung SPECT].
AB  - OBJECTIVE: 89Sr bremsstrahlung SPECT imaging has been evaluated for detecting the
      more detailed whole body 89Sr distribution. METHODS: 89Sr bremsstrahlung whole
      body planar and merged SPECT images were acquired by using two detectors type
      SPECT system. Energy window A (100 keV +/- 50%) for planar imaging, and energy
      window A plus adjacent energy window B (300 keV +/- 50%) for SPECT imaging were
      set on the continuous spectrum. Those images were compared with 99mTc-H-MDP whole
      body planar and merged SPECT images. To verify the accumulation obtained by
      bremsstrahlung whole body planar and merged SPECT image, we made original phantom
      based on the counts of clinical study imaging. RESULTS: On 89Sr bremsstrahlung
      merged SPECT image, focal accumulations were recognized in the parts of 99mTc-H
      MDP merged SPECT accumulation. Focal accumulations were much clearer on 89Sr
      bremsstrahlung merged SPECT imaging than those of whole body planar image of 89Sr
      bremsstrahlung. In phantom study, counts of each concentration linearly increase
      as acquisition time and number of rotation increase on planar and SPECT images.
      CONCLUSIONS: 89Sr bremsstrahlung merged SPECT imaging would be useful for
      detecting the more detailed whole body 89Sr distribution.

PMID- 21736041
TI  - [Decommissioning of the medical cyclotron in National Center of Neurology and
      Psychiatry].
AB  - OBJECTIVE: In Japan, positron emission tomography has prevailed as a useful
      procedure for detecting malignancy, myocardial viability, and epileptic foci.
      Consequently, compact medical cyclotrons have been installed in many hospitals.
      However, reports about the dismantling or decommissioning of compact medical
      cyclotrons are rare. This report describes the series of steps involved in the
      decommissioning of a compact medical cyclotron that had been used to produce
      radioactively tagged substances over a period of fifteen years at the National
      Center of Neurology and Psychiatry in Japan. Additionally, this report describes
      the manner in which the radioactive waste was disposed. METHOD: The plan to
      decommission the cyclotron was comprised of three phases: a preliminary survey,
      the dismantling work, and a reports after the dismantling. We complied with the
      guidelines for the disposal of radioactive waste published by the Ministry of
      Education, Culture, Sports, Science and Technology. RESULT: The most radioactive
      material was the vacuuming foil used in the window of the target chamber, with a
      dose rate of 17 microSv/h (gamma rays) and 20 x 10(3) cpm (beta rays). The
      detected radionuclides were mainly 22Na, 57Co, 60Co and 65Zn. The total numbers
      of radioactive waste containers were thirteen 200 l containers and one 50 l
      container. We suspect that the long shutdown period of the cyclotron (more than
      one year) contributed to the decay of the radioactive waste because the amount of
      containers was smaller than the initial estimation. CONCLUSIONS: The shutdown
      period of a cyclotron may play a significant role in reducing the amount of
      radioactive waste.

PMID- 21736043
TI  - [Pros/Cons debate: hyperbaric oxygen for carbon monoxide poisoning. Brief history
      of carbon monoxide poisoning and hyperbaric oxygen therapy].

PMID- 21736042
TI  - [Utilization of radionuclide therapy facility and assembly-temporary type
      therapeutic facility for medical treatment of radioactivity contaminated patients
      in nuclear emergency].
AB  - Medical management of patients internally contaminated in nuclear emergency
      needs, in addition to general medical treatment, to evaluate doses due to intakes
      of radioactive materials, to conduct effective treatment with stable isotopes and
      chelating agents and to keep public away from radioactive materials in and
      excreted from patients. The idea of medical treatment for internal contamination
      is demonstrated in the general principles on medical management of victims in
      nuclear emergency issued by the Cabinet Office in Japan. However, if impressive
      number patients with internal contamination are generated, the current medical
      management scheme in nuclear emergency is not able to admit them. The utilization
      of radionuclide therapy facilities where patients with thyroid diseases are
      treated with radioisotope and assembly-temporary housing type treatment
      facilities dedicated for internal contaminated patients may be expected to
      complement the medical management scheme in nuclear emergency. The effect or more
      medical management system for patients internally contaminated may become one of
      the safety nets in the contemporary society that inclines to use nuclear energy
      on account of accessibility.

PMID- 21736044
TI  - [Pros/Cons debate: hyperbaric oxygen for carbon monoxide poisoning. Pros: what
      should we learn from current researches?].

PMID- 21736045
TI  - [Pros/cons debate: hyperbaric oxygen for carbon monoxide poisoning. Cons].

PMID- 21736046
TI  - [Commencement of Diplomate of Japanese Society for Clinical Toxicology (DJSCT).
      What's to be discussed?].

PMID- 21736047
TI  - [From the standpoint of a physician: "Diplomate of Japanese Society for Clinical
      Toxicology" project--its overview and prospect].

PMID- 21736048
TI  - [From the standpoint of a pharmacist: the role of pharmacists in clinical
      practice].

PMID- 21736049
TI  - [From the standpoint of a pharmacist: a long awaited news for us].

PMID- 21736050
TI  - [From the standpoint of a chemical analyst: a realistic discussion].

PMID- 21736051
TI  - [From the standpoint of an analytical toxicologist: the current and future
      scope].

PMID- 21736052
TI  - [Hemopurification].

PMID- 21736053
TI  - Award-winning customer service: Stanford Hospital & Clinics.

PMID- 21736054
TI  - Developing a culture of revenue cycle excellence.

PMID- 21736055
TI  - Care management and the revenue cycle.

PMID- 21736056
TI  - New technologies reduce bad-debt risk and collection costs.

PMID- 21736057
TI  - [A pronounced scar in an 80-year-old patient. (Not) a saber wound. Scleroderma en
      coup de sabre].

PMID- 21736058
TI  - [When psychosocial stresses cause illness. Prevention of infarct of the soul].

PMID- 21736059
TI  - [Conserving resources and regular training. This way COPD patients master daily
      routine better].

PMID- 21736060
TI  - [Baby with a heart murmur. When you can reassure the parents].

PMID- 21736061
TI  - [After bypass surgery nearly all lipids are in the normal range. However, Lp(a)
      is too high, what can be done?].

PMID- 21736062
TI  - [Differentiated target values--differentiated treatment of lipid disorders.
      Diagnosis and treatment of diabetes are now on the move].

PMID- 21736063
TI  - [Hemoglobin A(1c)--a new tool in diagnosing diabetes].

PMID- 21736064
TI  - [Diabetic dyslipoproteinemia].

PMID- 21736065
TI  - [Anthropology in forensic problems].

PMID- 21736066
TI  - [Treatment of secondary restless legs syndrome].

PMID- 21736067
TI  - [Opiates in the treatment of non-cancer-related pain].

PMID- 21736068
TI  - Docs sporting a new message: participative aerobic exercise.

PMID- 21736069
TI  - 45 seconds: memoirs of an ER physician. When the deadly EF-5 tornado struck
      Joplin, May 22, 2011.

PMID- 21736070
TI  - A decade of extraordinary progress: biosciences in the Greater Kansas City
      region.
AB  - The Greater Kansas City region has made significant progress as a national center
      for animal health and the biosciences. Each of our stakeholder institutions have
      continued to make significant advances in key programs, which collectively have
      elevated the region's bioscience effort, with total R&D expenditures approaching
      $500M. In considering the future, through collaborative efforts the region will
      continue to advance and build upon the major successes, while seeking additional
      opportunities to leverage regional and institutional strengths. Further progress
      will be reported at the KCALSI website.

PMID- 21736071
TI  - Should doctors unionize for the purposes of collective bargaining?

PMID- 21736072
TI  - Primary care sports medicine fellowships. Their importance in becoming a team
      physician.

PMID- 21736073
TI  - Sports medicine from an orthopedic perspective.

PMID- 21736074
TI  - Upper extremity injuries in the throwing athlete.
AB  - Upper extremity injuries tend to take more time to recover from, and this is even
      more so in a throwing athlete. Specific injuries of the shoulder and elbow that
      are common in the throwing athlete are discussed and how advancements in
      diagnostic and surgical technology have allowed a quicker, more reliable return
      for a throwing athlete to their previous level of activity.

PMID- 21736075
TI  - Rehabilitation of the athlete.
AB  - Rehabilitation of an athlete after an injury takes a team approach for a
      successful return to competition. The five steps of rehabilitation are discussed,
      including diagnosis, control of inflammation, promote healing, increase fitness,
      and control abuse. Return to activity can occur once these things are
      accomplished and everyone is in agreement.

PMID- 21736076
TI  - Too much of a good thing: female athlete triad.
AB  - The history and pathophysiology of the Female Athletic Triad is discussed along
      with the short-term and long-term complications. The work-up for hormonal
      abnormalities and specific treatment options are discussed. Also, nutrition and
      its affect on the Female Athletic Triad is mentioned within the realm of
      treatment.

PMID- 21736077
TI  - When core measures fail: how often has the patient received the prescribed care?
AB  - Core measures were developed to assess the gap between recommended best medical
      practice and actual applied care using publicly-reported hospital results We
      found that 29+/-6% (p>0.001), of failed core measure cases actually received best
      medical practice care but failed documentation requirements.

PMID- 21736078
TI  - Has open vascular surgery disappeared?
AB  - In the era of evolutionary endovascular techniques, the evidence from most recent
      prospective randomized clinic trials supports the fact that both open and
      endovascular surgery are playing an important role in modern vascular patient
      care. The clinical data analysis from the University of Missouri further proves
      the fact that vascular surgeons are empowered by endovascular techniques to
      better serve the vascular patient in combination with traditional open
      techniques.

PMID- 21736079
TI  - Glioblastoma: Part I. Current state of affairs.
AB  - Although uncommon, "brain cancer" is one of the most feared diseases that afflict
      human beings. While still regarded as one of the most deadly forms of primary
      brain neoplasm, recent advances in the treatment of glioblastoma (GBM) have
      offered new hope for patients, families, and clinicians. In the first part of
      this two-part review, we will focus on the multidisciplinary advances that have
      established the current treatment approach in the management of GBM. In the
      second part of this review, ongoing research will be presented including current
      clinical trials as well as some of the newer technologies that are forming the
      promise of the future.

PMID- 21736080
TI  - Hepatocellular carcinoma: a review of the surgical approaches to management.
AB  - Hepatocellular carcinoma (HCC) is increasing in incidence in the United States
      and is strongly associated with chronic liver disease and cirrhosis. Surgical
      therapy with liver transplantation or resection remains the mainstay of curative
      therapy for patients with HCC. Therapeutic decisions in patients with HCC are
      complex and are best approached via a multidisciplinary group of liver transplant
      and hepatobiliary surgeons, oncologists, and hepatologists. In this manuscript,
      we review the current surgical management of HCC.

PMID- 21736081
TI  - Tobacco use among Missouri middle and high school students, 2003-2009.
AB  - Reducing tobacco use among young people is an important public health goal. This
      article summarizes the results of the analysis of Missouri Youth Tobacco Survey
      (YTS) data collected between 2003 and 2009. The YTS collects information
      regarding tobacco use and related issues among Missouri public middle and high
      school students. Downward trends in initiation of tobacco use and current
      cigarette smoking occurred during this period. However, increased implementation
      of evidence-based interventions is needed to continue the progress seen during
      this period.

PMID- 21736082
TI  - State of the Association: Presidential Address. The 153-rd Annual Convention,
      Missouri.

PMID- 21736083
TI  - Health care reform: what now?

PMID- 21736084
TI  - Comparative effectiveness research.

PMID- 21736085
TI  - Is the caesarean section rate in Ireland too high?

PMID- 21736086
TI  - Significant achievements in breast cancer care in Ireland.

PMID- 21736087
TI  - Gastric pacing for diabetic gastroparesis--does it work?
AB  - The management of diabetic gastroparesis resistant to medical therapy is very
      difficult Gastric electrical stimulation (GES) is a relatively new therapeutic
      modality which has shown some promise in international trials. It has seen use in
      four patients in Ireland. Our aim was to determine if GES improved patients'
      outcomes in terms of duration and cost of inpatient stay and glycaemic control.
      We reviewed the patients' case notes and calculated the number of days spent as
      an inpatient with symptomatic gastroparesis pre and post pacemaker, the total
      cost of these admissions, and patients' average HbA1c pre and post GES. Mean
      length of stay in the year pre GES was 81.75 days and 62.25 days in the year post
      GES (p=0.89). There was also no improvement in glycaemic control following GES.
      GES has been ineffective in improving length of inpatient stay and glycaemic
      control in our small patient cohort.

PMID- 21736088
TI  - Audit of outcomes from pre-school stammering intervention in a defined catchment
      population in the west of Ireland.
AB  - We have carried out an audit of outcomes from a pre-school stammering
      intervention offered to all 64 children, aged under 5 years referred from a
      defined catchment population to a single speech and language therapist over an 11
      year period (1993 -2003 inclusive). Therapy was based on a client centred
      eclectic approach which combines elements of direct therapy focused on the
      child's speech and a number of indirect approaches to treatment which focus on
      changing the child's environment. Follow-up was conducted by means of a short
      questionnaire to the parents. Non responders were assessed informally by a school
      nurse with responsibility for the clinic catchment area. Questionnaires were
      returned for 46 of the 64 children in the audit, of whom 43 were reported as not
      stammering, 2 with persistent stammer and there was one child with missing data
      on fluency status. No stammering was detected by the school nurse in the 18 non
      respondents. Thus 61 of the 63 children (97%; 95% C.I. 88.9% to 99.6%) with
      documented fluency status were reported as free of stammer at follow-up. These
      outcomes exceed natural recovery rates and highlight the importance of early
      referral of children with pre-school stammering to a specialist speech and
      language clinic

PMID- 21736089
TI  - Alcohol attributable hospitalisations and costs in Ireland, 2000-2004.
AB  - The aim of this study was to calculate the number and costs of hospital bed-days
      due to alcohol use in Ireland over the five year period 2000 to 2004. Age and sex
      specific Irish alcohol-attributable-fractions (AAFs) were developed by combining
      international risk estimates with Irish consumption data where available; where
      not available international AAFs were used. These were applied to national
      datasets to count the number and costs of bed-days wholly caused and prevented by
      alcohol and that proportion of bed-days that were partially caused and prevented
      by alcohol. Between 2000 and 2004, alcohol was estimated to have caused 3,428,973
      (10.3%) and prevented 529,239 (1.6%) of hospital bed-days, giving a net number of
      bed-days due to alcohol of 2,899,734 (8.7%). Over this period the hospital
      inpatient costs attributed to the negative effects of alcohol were 953,126,381
      euros, the costs attributed to hospitalisations prevented were 147,968,164 euros;
      giving net costs of alcohol-attributed bed-days of 805,158,217 euros. Chronic
      conditions accounted for 3,262,408 (95%) hospital bed-days due to the harmful
      effects of alcohol. Conditions not wholly due to alcohol accounted for 2,297,412
      (67%) hospital bed-days due to the harmful effects of alcohol. The negative
      impacts of alcohol were greater than previously thought and spread across the
      whole population.

PMID- 21736090
TI  - Hepatitis C: is there a case for universal screening in pregnancy?
AB  - Hepatitis C (HCV) is not routinely screened for antenatally in all maternity
      hospitals. Most hospitals adopt a policy of targeted screening. The policy in the
      Coombe Women and Infants University Hospital in Dublin changed from targeted
      screening in 2006 to universal screening in 2007. We audited the two consecutive
      years. The prevalence of HCV in our antenatal population was 1.4% for 2006
      (67/4666) when targeted screening applied and in 2007--0.71% (66/9222) when
      universal screening came into affect. One woman in 2007 would not have been
      detected by targeted screening--1.49% (1/67). Fifty five percent (37/67) of women
      were HCV-RNA positive in 2006 and 57.5% (38/66) were positive in 2007. We
      conclude that there were similar detection rates for HCV in 2006 and 2007 and
      that universal screening is not required if inclusive criteria for selective
      screening are employed but is of use in research context.

PMID- 21736091
TI  - Intravitreal anti-VEGF therapy for neovascular age-related macular degeneration
      and the risk of stroke.
AB  - The purpose of this study was to compare the vascular event rate in AMD patients
      treated with an intravitreal VEGF inhibitor with a historical control group
      treated with photodynamic therapy. We reviewed medical records of 83 patients
      treated with intravitreal anti-VEGF for AMD between 2005-2007, and 60 patients
      treated with PDT between 2001-2004. Mean follow-up in the anti-VEGF group was 40
      months versus 95 months in the PDT group. Mean age (76 +/- 9 years, versus 74 +/-
      10 years, p=n.s.) and cardiovascular risk factor profile were similar. Vascular
      event rates in each group were 2.6 per 100 patient years versus 2.3 per 100
      patient years, (p = n.s). Age over 80 years was associated with an increased risk
      of a vascular event (odds ratio = 1.113, p<0.05). Despite the high prevalence of
      risk factors in AMD patients, the incidence of vascular events was low and
      associated with older age rather than therapy received.

PMID- 21736092
TI  - Is neonatal group B streptococcal infection preventable?
AB  - Early onset group B streptococcal (EOGBS) infection causes significant neonatal
      morbidity and mortality. We determined the incidence of EOGBS at Galway
      University Hospital (GUH) and examined any "missed opportunities" for preventing
      neonatal infection between 2004 and 2009. Our obstetric approach is risk-based.
      The incidence was 0.45/1,000 live-births; one death and one with neurological
      sequelae. A single mother received IAP; however we could not determine any
      potential for reducing cases of EOGBS by improving current IAP usage.

PMID- 21736093
TI  - Exercise induced fatigue: unfit or unwell?
AB  - This case report outlines the diagnoses of a rare myophosphorylase deficiency
      (McArdle Syndrome) in a unique way. A set of characteristic values from a
      Cardiopulmonary Exercise Test (CPET) combined with a typical patient history
      pointed to a failure of the glycolytic pathway in the skeletal muscle. McArdle
      Syndrome was confirmed with a skeletal muscle biopsy. There is no evidence of
      such a diagnostic method in the literature.

PMID- 21736094
TI  - An unusual cause of spontaneous pneumothorax: the Mounier-Kuhn syndrome.
AB  - We present the case of a 54-year old woman referred to our service with an
      unusual presentation of an under-diagnosed condition. A life-long non-smoker, she
      was referred to respiratory services by our emergency department with a left
      sided pneumothorax, progressive dyspnoea on exertion, and recurrent chest
      infections. Subsequent investigation yielded findings consistent with Mounier
      Kuhn syndrome (Tracheobronchomegaly), a condition characterised by marked
      dilatation of the proximal airways, recurrent chest infection, and consequent
      emphysema and bronchiectasis. Although rarely diagnosed, some degree of Mounier
      Kuhn syndrome may occur in up to 1 in 500 adults.

PMID- 21736095
TI  - Vertroplasty for spinal fracture.

PMID- 21736097
TI  - Taking a pragmatic approach.

PMID- 21736096
TI  - 12 month prevalence of drug use among third-level students in Limerick City.

PMID- 21736098
TI  - Workloads and staff levels hamper dementia care.

PMID- 21736099
TI  - Pathway to excellence.

PMID- 21736100
TI  - Practice question. Peri-operative care. How can ward nurses improve the care of
      older surgical patients?

PMID- 21736101
TI  - Use of hypodermoclysis to manage dehydration.
AB  - Older people, particularly those who are frail, are vulnerable to dehydration.
      Management of dehydration in older people can be more complex than in younger
      adults because of the physical effects of ageing. As the population ages, nurses
      will increasingly care for older patients in every setting. This article provides
      an overview of the physiological changes that affect the ability of older people
      to maintain a normal fluid balance. Risk factors for dehydration are reviewed and
      strategies for the prevention, detection and management of dehydration are
      discussed. The article focuses on subcutaneous fluid replacement for the
      management of dehydration in older adults.

PMID- 21736102
TI  - How community matrons perceive their effectiveness in case management.
AB  - AIM: The aim of this study was to explore community matrons' experience of
      caseload management and identify situations that may restrict or enhance patient
      care and outcomes. The Department of Health advises that community matrons should
      have a caseload of 50, based on the Evercare model from the US. However, there is
      little evidence to justify this caseload target. METHOD: A phenomenological
      approach was adopted to analyse data from interviews with six community matrons
      based in two south west primary care trusts. Maximum variation sampling was used.
      FINDINGS: There are difficulties in building and maintaining a caseload of 50
      complex patients with long-term conditions. The higher the caseload the less
      effective the community matrons perceived themselves to be in reducing hospital
      admissions. CONCLUSION: Targets should not be set from similar models such as
      Evercare. A more integrated approach is required with the service being available
      24 hours a day. Further research is required to identify the most appropriate
      caseload size and the of managing such high-risk patients. Quantitative research
      would help to determine the effect of variables.

PMID- 21736103
TI  - The use of emollient therapy for ageing skin.
AB  - Skin ageing has intrinsic signs and symptoms, often complicated by extrinsic
      photo-ageing symptoms and concurrent disease processes. It progresses with age
      but varies between individuals and its symptoms are numerous. Skin ageing has
      physical and psychosocial repercussions that can influence coping. Emollient
      therapy can help to reduce two symptoms--dryness and loss of the skin's barrier
      function. Better understanding of skin ageing and the usefulness of emollients
      can be reinforced by education and encouragement from healthcare professionals.
      Such interventions should encourage self-management and confidence in using
      emollients. The partnership between healthcare professionals and older people
      helps to overcome co-existent ageing difficulties, such as cognitive impairment,
      hearing loss and impairment of manual dexterity and mobility, which enhances self
      reliance.

PMID- 21736104
TI  - Navigating the journey.

PMID- 21736105
TI  - Constitution needs full member vote.

PMID- 21736106
TI  - Choosing healing and recovery.

PMID- 21736107
TI  - Naturopath gives good advice.

PMID- 21736108
TI  - Earthquake 2011.

PMID- 21736109
TI  - Meeting the demand of rural palliative care nursing.

PMID- 21736110
TI  - Ensuring a dignified and culturally safe death.

PMID- 21736111
TI  - Examining end-of-life care issues.

PMID- 21736112
TI  - Blood transfusion: the high-risk life-saving therapy.

PMID- 21736113
TI  - Empowering local people to run a mobile palliative care service.

PMID- 21736114
TI  - Florence had a vocation--she was born to lead.

PMID- 21736116
TI  - Reducing medication errors.

PMID- 21736115
TI  - Education and employment--what does the future hold?

PMID- 21736117
TI  - NZNO direct--a better way to communicate.

PMID- 21736118
TI  - In support of the MDA's access to care priorities: a proposal to expand HKD to
      all counties.

PMID- 21736119
TI  - Legal responsibility for unclaimed property.

PMID- 21736120
TI  - The Americans with Disability Act, updated.

PMID- 21736121
TI  - Why should I care about peer review?

PMID- 21736122
TI  - The importance of making the right beneficiary decision.

PMID- 21736123
TI  - Researchers connect a specific protein to head and neck cancers.

PMID- 21736124
TI  - Should parents of pediatric patients be permitted in the operatory?

PMID- 21736125
TI  - Oral pathology quiz #24. Squamous cell carcinoma.

PMID- 21736126
TI  - Help when you need it: the MDA COVER program.

PMID- 21736127
TI  - What becomes 'bundle worthy?'.

PMID- 21736128
TI  - Medicare forecast: dark clouds rolling in faster than previously thought.

PMID- 21736129
TI  - Diabetes: CKD's main cause is on the rise. A look from experts at different
      aspects of diabetes-related kidney care.

PMID- 21736130
TI  - Q&A with Robert G. Nelson, MD, PhD.

PMID- 21736131
TI  - Management of diabetes-related chronic kidney disease.

PMID- 21736132
TI  - Part 2. The promise of symptom-targeted intervention to manage depression in
      dialysis patients: improving mood and quality of life outcomes.
AB  - The Practice Outcome Evaluation of using Symptom Targeted Intervention (STI) to
      manage depressed mood in dialysis patients reviewed social worker experiences and
      observations using STI. The evaluation was guided by the following questions: 1.
      What is the feasibility of STI in nephrology social work? 2. What is nephrology
      social worker comfort level with clinical assessment, intervention, and tracking?
      3. What is the potential efficacy of STI on reducing depression? Initial results
      suggest that STI enhances existing nephrology social work skills in identifying,
      treating, and tracking outcomes of patient issues requiring clinical
      intervention. Most social workers spent 1.5 hours over a six-week period using
      STI techniques to address symptoms of depression with a patient. This rather
      short period of intervention led to a reported improvement in PCS and MCS scores
      of 51.6% and 61.3% of patients, respectively, and improvement in CES-D scores in
      72.1% of patients. While this practice outcome evaluation is limited by how
      social workers were selected and the small number of patients, it demonstrates
      options for further study of the efficacy of STI in reducing depression. The
      brief time invested in training holds promise for impacting nephrology social
      work and improving patient and dialysis clinics' outcomes.

PMID- 21736133
TI  - The ESRD demonstration project: what it accomplished. Fresenius Medical Care
      North America.

PMID- 21736134
TI  - Can an integrated care model improve patient care?

PMID- 21736135
TI  - The ESRD Demonstration Project: what it accomplished. DaVita Inc.

PMID- 21736137
TI  - Off the beaten path: conducting ethical pragmatic trials with marginalized
      populations.

PMID- 21736136
TI  - Broad data sharing in genetic research: views of institutional review board
      professionals.

PMID- 21736138
TI  - Parents' understanding and recall of informed consent information for neonatal
      research.

PMID- 21736139
TI  - The $80 billion question.

PMID- 21736140
TI  - HIT vendors scramble for positioning.

PMID- 21736141
TI  - Preserving EHRs: time to worry?

PMID- 21736142
TI  - Carts doing heavy lifting today, but tomorrow?

PMID- 21736143
TI  - Clearing the way.

PMID- 21736144
TI  - Boosting ED service--and revenue.

PMID- 21736145
TI  - No business like I.T. business. Interview by Elizabeth Gardner.

PMID- 21736146
TI  - Generous light.

PMID- 21736147
TI  - I couldn't have said it better myself!

PMID- 21736148
TI  - Eye surgery is for eye surgeons: an open letter to the public.

PMID- 21736149
TI  - A review of the American Heart Association revised guidelines for the prevention
      of infective endocarditis.

PMID- 21736150
TI  - A young male with sudden onset left-sided weakness.

PMID- 21736151
TI  - Free muscle flap reconstructions using interpositional vein grafts vs. local
      anastomosis: a 5-year experience at a rural tertiary care center.
AB  - BACKGROUND: The use of free muscle or myocutaneous flaps is well established as a
      means for reconstructing tissue defects over nearly any part of the body. This
      free tissue transfer is based on the availability of a robust blood supply in the
      recipient wound. The reliability of native blood supplies within the zone of
      injury is suspect even in the best of conditions. There are several causes of
      flap failure however; one of the most common is vascular compromise. Though
      refinements in the technique of vascular anastomosis have lessened the risk, it
      is still significant, especially when dealing with an area of injury at the
      recipient site. The mechanisms of scar formation and healing that occur within
      the zone of injury often limit the potential for viable anastomotic targets. This
      often leads to delay in wound coverage and exposes the patient to all of the
      risks associated with having an open wound. Free flap failure can be devastating
      for patients, even leading to the loss of limbs. Therefore, it is vital that all
      measures possible to ensure the survival of the transferred tissue be employed.
      METHODS: We will examine interpositional vein grafts versus local anastomoses in
      the context of free tissue transfer for wound coverage in the traumatized and
      reconstructed patient. We will retrospectively review the case histories of free
      tissue transfers preformed at West Virginia University Hospital over a 5-year
      period (2001-2006). We will examine data including the demographics of our
      patient population, type and locations of the free flaps, length of stay in the
      hospital, time interval between injury and repair, and the Success and failure
      rate. RESULTS: The overall success rate was 38 out of 45 or 84%. Success was
      defined as a healthy flap and preservation of the limb and/or successful wound
      coverage at time of discharge. Flap success was present in 18 of 23 (78%) of the
      vein interposition grafts, and flap failure occurred in 5 (22%). In patients with
      local anastomoses, 20 out of 22 flaps survived (91%) with 2 failures (9%). GOALS:
      We will demonstrate that the use of interpositional vein grafts for free tissue
      transfer is a viable option in the wound coverage. We will demonstrate that this
      is especially 'true in the patient population that exists in rural America.

PMID- 21736152
TI  - Successful pregnancy following conservative surgical therapy of an invasive molar
      gestation.
AB  - BACKGROUND: An invasive mole is a form of persistent trophoblastic disease. The
      traditional surgical treatment is hysterectomy. CASE: A young nullipara presented
      with a positive pregnancy test 6 months following a suction curettage for an
      incomplete abortion. Radiologic imaging was suspicious for intramural ectopic
      gestation. She was treated with methotrexate but became thrombocytopenic with
      failure to resolve the abnormal gestation. Surgical excision of the mass was
      performed. Pathologic evaluation revealed the diagnosis of invasive molar
      pregnancy. The beta-hCG levels remained negative for greater than a year. The
      patient subsequently conceived and underwent a cesarean delivery of a viable
      infant at 36 weeks gestation. CONCLUSION: Conservative surgical excision can
      successfully treat invasive molar gestation. This should be considered for
      patients who desire future fertility and have contraindications to medical
      therapy.

PMID- 21736153
TI  - Geographic and temporal comparisons of ATV deaths in West Virginia, 2000-2008.
AB  - During the 9-year period from 2000-2008, West Virginia experienced 301 deaths
      related to All-terrain Vehicles (ATVs). The distribution of ATV deaths across the
      top 20 counties in West Virginia accounted for nearly seventy percent of the ATV
      related deaths during the 9-year study period. Time-of-day was a significant
      predictor of population-based rates, and a 34% decrease in the fatality rate from
      2.94 in 2006 to 1.93 in 2008 occurred. We opine that the decline in ATV mortality
      is possibly due to better enforcement of the (WV Code Chapter 17F), mandatory ATV
      regulations passed by the West Virginia State Legislature in 2004. Improved
      safety vigilance and ATV operator adherence to manufacturers' safety guidelines
      may have also contributed to the decreasing incidence of ATV deaths. While the
      current downward trend is most welcome, more attention should be directed towards
      high-risk behaviors including alcohol and drug abuse and driving on paved
      surfaces.

PMID- 21736154
TI  - Finding a faster route to practice: from medical student to board certified
      physician.
AB  - An examination of two types of educational tracks used by medical students
      seeking a faster route to practice: 1) "3+3" programs that combined the final
      year of medical school with the first year of a primary care residency, and 2)
      graduating from medical school after only three years. The "3+3" programs were
      discontinued despite reports indicating their success. Three year medical school
      options are still available at a handful of medical schools. Finally, the paper
      will explore why and how medical schools might wish to enact a three year
      curricular option.

PMID- 21736155
TI  - Wheeling Jesuit University Health Center adopts electronic medical records.

PMID- 21736156
TI  - Health system reform and its impact on West Virginia.

PMID- 21736157
TI  - MU's Chapmanville Center to provide care, teaching.

PMID- 21736158
TI  - West Virginia Health Statistics Center Child Asthma Survey enables development of
      state asthma plan.

PMID- 21736159
TI  - Customer service in the medical office.

PMID- 21736160
TI  - Medical devices; exception from general requirements for informed consent. Final
      rule.
AB  - The Food and Drug Administration (FDA) is issuing a final regulation to confirm,
      with one change, the interim final rule (IFR) entitled "Medical Devices;
      Exception From General Requirements for Informed Consent." This final rule
      confirms the IFR's establishment of a new exception from the general requirements
      for informed consent to permit the use of investigational in vitro diagnostic
      devices to identify chemical, biological, radiological, or nuclear agents without
      informed consent in certain circumstances. FDA has created this exception to help
      ensure that individuals who may have been exposed to a chemical, biological,
      radiological, or nuclear agent are able to benefit from the timely use of the
      most appropriate diagnostic devices, including those that are investigational.
      This final rule adds a requirement that the investigator submit the required
      documentation to FDA, in addition to submitting it to the reviewing Institutional
      Review Board (IRB).

PMID- 21736161
TI  - Reimbursement offsets for medical care or services. Final rule.
AB  - This document amends the regulations of the Department of Veterans Affairs (VA)
      concerning the reimbursement of medical care and services delivered to veterans
      for nonservice-connected conditions. This rule applies in situations where third
      party payers are required to reimburse VA for costs related to care provided by
      VA to a veteran covered under the third-party payer's plan. This final rule adds
      a new section barring offsets by third-party payers and requires that third-party
      payers submit a request for a refund for claims when there is an alleged
      overpayment.

PMID- 21736162
TI  - Group health plans and health insurance issuers: rules relating to internal
      claims and appeals and external review processes. Amendment to interim final
      rules with request for comments.
AB  - This document contains amendments to interim final regulations implementing the
      requirements regarding internal claims and appeals and external review processes
      for group health plans and health insurance coverage in the group and individual
      markets under provisions of the Affordable Care Act. These rules are intended to
      respond to feedback from a wide range of stakeholders on the interim final
      regulations and to assist plans and issuers in coming into full compliance with
      the law through an orderly and expeditious implementation process.

PMID- 21736163
TI  - Abstracts of Occupational Therapy Australia, the 24th National Conference and
      Exhibition. June 29-July 1, 2011. Gold Coast, Queensland, Australia.

PMID- 21736164
TI  - Lansley has yet to convince us.

PMID- 21736165
TI  - Cuts in specialist nursing likely to push more patients into acute care, warns
      RCN.

PMID- 21736166
TI  - Turning on nursing innovation to improve care and efficiency.

PMID- 21736167
TI  - Preventing venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a significant cause of long-term disability,
      chronic ill health and mortality, causing about 25,000 deaths a year in hospitals
      in England. It is recognised as a clinical priority for the NHS by the National
      Quality Board, which established a VTE board to mainstream and embed VTE
      prevention in NHS activity by 2012 (Keogh 2011) through the national VTE
      programme. This article describes NHS East of England's approach to implementing
      the programme.

PMID- 21736168
TI  - The policy and practice of measuring patient experience.
AB  - The NHS outcomes framework makes clear that the provision of a 'good experience'
      of care for patients, alongside clinical effectiveness and safety, is a central
      goal for the NHS. Developing a comprehensive strategy for measuring patient
      experience requires a decision about what should be measured and how. This
      article discusses current policy direction and its implications for practice, and
      sets out the fundamentals of measuring patient experience.

PMID- 21736169
TI  - Fostering teamwork in an intermediate care unit.
AB  - The government has emphasised that, to deliver high quality, integrated care,
      staff must work across organisational boundaries using a team approach so that
      everyone works towards the same goals. This article describes how one NHS-managed
      intermediate care unit has integrated care staff employed by the independent
      sector.

PMID- 21736170
TI  - Using enter-and-view provision to review hospital nutritional care.
AB  - Local involvement network (LINk) representatives can enter health or social care
      services to view the quality of the service provided. In late 2010, South
      Gloucestershire LINk used its enter-and-view power to look at inpatient nutrition
      and hydration in North Bristol NHS Trust. Authorised LINk representatives
      scrutinised trust policy documents, met with board members, senior staff and
      matrons, visited wards to observe mealtimes, and talked to ward staff and
      patients. They found that nutritional screening is being implemented across the
      trust and protected mealtimes are in place. They recommended, however, the
      introduction of a universal system of identifying patients who need help to eat
      and drink, that qualified staff note every patient's food wastage, and that staff
      should make minor changes to practice to help patients drink fresh tap water
      regularly.

PMID- 21736171
TI  - Managers' duty to maintain good workplace communications skills.
AB  - Communication is a fundamental element of care at every level of nursing
      practice. It is important, therefore, for nurse managers to create environments
      that promote and encourage good communication, and help nurses to develop their
      communication skills formally and informally. This article discusses the effects
      of communication on the quality of care. It examines nurses' professional duty to
      maintain good communication skills and how managers can help them do this. It
      also discusses nurse managers' communication skills in the context of leadership
      style, conflict resolution and self-awareness. Finally, it considers the notion
      of shared governance as good practice.

PMID- 21736172
TI  - The best job I've had. Interview by Ruth Williams.

PMID- 21736173
TI  - Doubling the number of nurses with a doctorate by 2020: predicting the right
      number or getting it right?

PMID- 21736174
TI  - Predictors of registered nurses' willingness to remain in nursing.
AB  - A major question about the adequacy of the future supply of nurses is how many
      will stay in the profession. The relationship between scheduling and propensity
      to stay or leave the nursing profession was examined in this study. This analysis
      suggests there are definite characteristics of the work schedules that can
      influence a nurse's inclination to stay or leave the profession. This is not
      simply a question of "overwork," but of matching work schedules and hours as
      closely as possible to employee expectations. This suggests management needs to
      find a way to pay attention when nurses request changes in hours. The mere fact
      of changing schedules will not solve the nursing shortage, but it is one action
      within the management control of any organization employing nurses that could
      have a positive effect on retention.

PMID- 21736175
TI  - Funding an accelerated baccalaureate nursing track for non-nursing college
      graduates: an academic/practice collaboration.
AB  - To expand nursing programs to better meet workforce demands, nursing education
      must offer nontraditional students more educational opportunities that are
      flexible, streamlined, and low cost. Accelerated programs, particularly programs
      tailored to attract individuals with degrees in other fields and looking for
      career changes, are great examples. The cost factors related to a successful
      accelerated degree program designed for non-nursing college graduates are
      described. Based on the experiences with a previously implemented accelerated BSN
      program offered from 1987-1994 at one university, a revised accelerated option
      model was developed that included ongoing involvement with four community
      hospitals, shared budget responsibilities, student stipends, and a 3-year work
      commitment by graduates at a sponsoring hospital. The investment of approximately
      $1.6 million over 7 years resulted in the education and graduation of 75 new
      registered nursing professionals to meet the health care needs of the citizens of
      the community.

PMID- 21736176
TI  - Implications of nurse-physician relations: report of a successful intervention.
AB  - Given the evidence linking medical errors to ineffective communication,
      strategies for improving communication among health care professionals must be
      implemented. The purpose of this article was to examine the effect of a
      collaborative intervention on improving communication patterns between nurses and
      physicians on two study units. The intervention consisted of two nurses and two
      physicians (per unit) meeting together (8 hours total) to collaboratively develop
      a solution to communication issues on their respective units. Physicians scored
      significantly higher on reports of openness of communication within groups,
      openness between groups, accuracy between groups, and collaboration between
      groups. Collaboration reported among nurses and physicians improved for both
      professions, with significance reached for physicians (p = 0.031). Strategies
      must be identified to break down the barriers set by the current culture, and
      that expedite the development of a team-centered culture supporting collaborative
      relations among health care professionals.

PMID- 21736177
TI  - Enhancing nursing as a career choice with fifth-grade students.
AB  - The purpose of this study was to explore the influence of a career education
      program on children's interest in nursing as a career choice, especially related
      to gender in fifth-grade students. A within-subjects design compared interest in
      nursing as a career of 70 fifth-grade students before and after participation in
      a 4-week career education program about nursing. There was a 61% (N = 70, p <
      0.001) increase of students expressing they would consider nursing as a career
      after participating in the career education program. This positive effect was
      discovered among both male and female students. Further results provided a pre
      and post-career assessment of the students' development that was congruent with
      findings from previous vocational studies. The results underscore the positive
      effect career education can have on children's career interests and substantiate
      the importance of exposing students to practicing nurses as a key strategy to
      stimulate interest in nursing to help maintain a steady recruitment of young
      people into the future nursing workforce.

PMID- 21736178
TI  - When caring stops, staffing doesn't matter: part II.
AB  - Response to a column on caring and staffing struck a cord with Nursing Economic$
      readers worldwide. Measuring caring is complicated and a healthy debate exists
      over how exactly to do it. The extraordinary work of Dr. Jean Watson is an
      excellent resource for understanding how to measure and monitor caring. Beneath
      the instruments for measuring caring sits foundational work that can help us
      clarify and understand the topic of caring and just where it sits in our
      philosophies, intentions, patient care models, and care delivery systems.

PMID- 21736179
TI  - Deconstructing health care reform.
AB  - As health reform is deconstructed, we need to stop and do some deconstructing of
      our thinking about it, looking at the context of our assumptions or frames. If we
      think of health as taking the supreme welfare of the people seriously, we will
      not allow it to be framed only in terms of for-profit interests and the status
      quo. Nurses have expertise and knowledge regarding what is needed for a quality
      health care system. We have to join the conversation with as many good questions
      as ideas. Working from a different frame, one that reflects more of your values,
      may give you new insights into holding the conversation.

PMID- 21736180
TI  - The nursing informatics workforce: who are they and what do they do?
AB  - Nursing informatics has evolved into an integral part of health care delivery and
      a differentiating factor in the selection, implementation, and evaluation of
      health IT that supports safe, high-quality, patient-centric care. New nursing
      informatics workforce data reveal changing dynamics in clinical experience, job
      responsibilities, applications, barriers to success, information, and
      compensation and benefits. In addition to the more traditional informatics nurse
      role, a new position has begun to emerge in the health care C-suite with the
      introduction of the chief nursing informatics officer (CNIO). The CNIO is the
      senior informatics nurse guiding the implementation and optimization of HIT
      systems for an organization. With their fused clinical and informatics
      background, informatics nurses and CNIOs are uniquely positioned to help with
      "meaningful use" initiatives which are so important to changing the face of
      health care in the United States.

PMID- 21736181
TI  - Thriving on innovative technology.

PMID- 21736182
TI  - Retraction of articles with misleading information.

PMID- 21736184
TI  - Independently owned pharmacy closures in rural America, 2003-2010.
AB  - The purpose of this policy brief is to provide policy makers, researchers, and
      stakeholders with information about the closure of rural independently owned
      pharmacies, including pharmacies that are the sole source of access to local
      pharmacy services, from 2003 through 2010. This period coincides with the
      implementation of two major policies related to payment for prescription
      medications: (1) Medicare prescription drug discount cards were introduced on
      January 1, 2004; and (2) the Medicare prescription drug benefit began on January
      1, 2006. In this brief, we focus on rural pharmacy closure because of the
      potential threat such closures present to access to any local pharmacy services
      in a community. Those services include providing medications as needed (not
      waiting for mail order), overseeing administration of medications to nursing
      homes and hospitals, and patient consultation.

PMID- 21736186
TI  - Education, workforce, and planning for the future.

PMID- 21736187
TI  - Dragged kicking and screaming into the ether.

PMID- 21736188
TI  - Maxillofacial oncology at the University of Minnesota: treating the epidemic of
      oral cancer.
AB  - INTRODUCTION: Oral cancer may present with a variety of signs and symptoms
      including pain, dysphagia, non-healing ulcers, red and white lesions, and
      indurated masses. Historically, oral cancer has been associated with the male
      population, particularly those who use tobacco and alcohol. Recently, there has
      been a dramatic increase in oral cancer rates seen in the population aged 40
      years and younger. This increase has not been associated with the traditional
      risk factors for oral cancer and is likely linked to etiologic factors that
      remain still undefined. The proliferation of oral cancer is also mirrored by an
      increase in oropharyngeal malignancies such as base of tongue and tonsil cancer,
      although the increase in this subset of patients appears to be clearly associated
      with Human Papillomavirus (HPV). METHODS: We present a summary of all oral
      malignancies treated at the University of Minnesota Oral and Maxillofacial
      Surgery Division from 2008 through early 2011. RESULTS: Since July of 2008, the
      Oral and Maxillofacial Surgery Department at the University of Minnesota has been
      referred a total of 69 cases of head and neck malignant tumors, of which 58 were
      primarily managed with surgery. A broad range of head and neck cancers were seen,
      with the most common being oral squamous cell carcinoma (OSCC), which accounted
      for 81% of patients treated by oncologic tumor resection. The tongue was the most
      common site of occurrence of OSCC with 33% of cases. There was an even
      distribution between genders. Traditional treatment modalities included surgical
      resection of primary tumors including neck dissection, when indicated, with
      postoperative adjuvant therapies being reserved for advanced stage tumors or high
      risk pathologic features for recurrence. At the conclusion of the study period in
      January, 2011, 83% of patients treated surgically for OSCC were living disease
      free, 4% had recurrent tumors not amenable to resection, 6% of patients had died
      from other causes, and 6% had succumbed to OSCC, resulting in a disease-specific
      survival rate of 93% with an overall survival rate of 87%. CONCLUSIONS: Oral
      cancer continues to be diagnosed with advanced stage disease in 50% of patients.
      Dental practitioners play a significant role in the early detection and diagnosis
      of oral cavity cancer. It is incumbent upon dental practitioners to be aware of
      the early signs and symptoms of oral cancer and to make prompt referral to head
      and neck cancer specialists when indicated. Diligent and frequent examination,
      particularly in patients with risk factors, will greatly improve survival rates
      and minimize the complexity and morbidity of oncologic treatment when patients
      are diagnosed with earlier stage disease.

PMID- 21736189
TI  - Why do we polish? Part one.
AB  - What does polishing oral hard tissues and restorations accomplish? The two parts
      of this review will describe the effect of polishing on various restorative
      materials and teeth; the development of biofilm and adherence of plaque to teeth
      and restorations; the effects of unpolished versus polished surfaces on gingival
      health and longevity of restoration; and techniques for polishing various
      restorative materials. A listing of available polishing materials is included in
      Part Two, which will appear in the July-August Northwest Dentistry.

PMID- 21736190
TI  - One man's treasure.

PMID- 21736191
TI  - Dentists planning for financial independence.

PMID- 21736192
TI  - What's a dentist to do? Comfort and hope.

PMID- 21736193
TI  - Romancing the sky.

PMID- 21736194
TI  - Issue calls for reasoned discussion, not politics.

PMID- 21736195
TI  - View from a thousand feet.

PMID- 21736196
TI  - Flight fellows.

PMID- 21736197
TI  - Air care.

PMID- 21736198
TI  - Pilot practices.

PMID- 21736199
TI  - Pressure work.

PMID- 21736200
TI  - Building health care homes.

PMID- 21736201
TI  - Court sides with clinic in legal fight with malpractice insurer.

PMID- 21736202
TI  - Midnight runner.

PMID- 21736203
TI  - Is there a doctor on board? Ten physicians share their stories about mid-air
      medical emergencies.

PMID- 21736204
TI  - Children and airplanes: are we having fun yet?
AB  - Health care providers are often asked by parents whether it is safe for their
      child to fly and what they can do to make air travel more pleasant for the child
      and for their fellow passengers. This article provides answers to seven
      frequently asked questions about children and air travel.

PMID- 21736205
TI  - When is it safe to fly? Addressing medical conditions in pilots.
AB  - Since World War I, the role of physicians who care for pilots has been to
      minimize the risks posed by the unique environment in airplanes and the demands
      of flying. Originally, that meant screening out those with any physical
      limitations that might affect their ability to fly such as vision or cardiac
      problems. Today, however, with the ability to better manage patients with
      multiple conditions, the physician's task is more nuanced and requires an
      estimation of risk based on the how well a pilot's condition can be managed and
      the type of flying he or she does. This article looks at how pilots are medically
      evaluated and how the standards for medical certification are evolving, allowing
      some pilots who have certain conditions to continue flying.

PMID- 21736206
TI  - Radiation exposure and air travel: should we worry?
AB  - With the federal government introducing new advanced imaging scanners at
      airports, the traveling public has become concerned about the radiation exposure
      they may receive when passing through scanners as well as during flight. This
      article offers a primer on radiation and the extent to which exposure from
      various sources can affect health. It also provides advice for physicians whose
      patients may have concerns about radiation exposure during air travel.

PMID- 21736207
TI  - Air travel and venous thromboembolism: minimizing the risk.
AB  - For those traveling on long flights, the risk of deep vein thrombosis or
      pulmonary embolism, generally referred to as venous thromboembolism (VTE), is
      real and dangerous if left unrecognized or untreated. The goal of this article is
      to provide an overview of how best to prevent VTE during travel, and how to
      diagnose and treat it.

PMID- 21736208
TI  - Healthcare informatics 100 companies by revenue. Vendors in healthcare IT: our
      annual ranking.

PMID- 21736209
TI  - Analysis: an early wave crest?

PMID- 21736210
TI  - M&A 2010: more buying, spending less.

PMID- 21736211
TI  - Breaking the mold.

PMID- 21736212
TI  - Clinical chimera: OptumInsight.

PMID- 21736213
TI  - Showing them evidence.

PMID- 21736214
TI  - Up and comers.

PMID- 21736215
TI  - Rethinking the vendor relationship.

PMID- 21736216
TI  - Meaningful change coming to public health.

PMID- 21736217
TI  - Comparative effectiveness: the rest of the story.

PMID- 21736218
TI  - CPOE and patient safety.

PMID- 21736219
TI  - Predicting future behavior.

PMID- 21736220
TI  - Healthy data helps patients and providers flourish. Keeping data verified, clean
      and secure is critical medic for today's complex patient information.

PMID- 21736221
TI  - Reform's new MLR mandates: challenge or opportunity? Healthcare reform will
      undoubtedly bring its share of challenges, but meeting the new medical loss ratio
      requirements doesn't have to be one of them.

PMID- 21736222
TI  - Help for incorporating medical devices into IT networks. New guidance shows how
      the risk-management process fits into the lifecycle of a shared network.

PMID- 21736223
TI  - The visitor: People have a right to live--and a right to die.

PMID- 21736224
TI  - A smile and a positive attitude: both have an important place in prehospital
      medicine.

PMID- 21736225
TI  - The near-death patient: a dying man's orders restrict his treatment--but what
      about during transport?

PMID- 21736226
TI  - Make 'em laugh, make 'em cry: Q&A with EMS cartoonist and author Steve Berry.

PMID- 21736227
TI  - Assessing the heart: Using a focused assessment, EMS providers can identify most
      cardiovascular emergencies.

PMID- 21736228
TI  - Hidden crisis: Ethics breakdown in Massachusetts.

PMID- 21736229
TI  - How to succeed in paramedic class: preparing for the challenging course ahead.

PMID- 21736230
TI  - Smoke inhalation. Part 2: patient management.

PMID- 21736231
TI  - Newborn resuscitation: the golden minute.
AB  - Delivering a new life into the world is truly a unique and proud moment, not just
      for the EMS providers who may do only one in their careers, but also for the
      parents, who probably did not think their new baby would be born outside the
      hospital.Due to the infrequency of delivering a baby in the prehospital
      environment, and even more rarely having to perform a major resuscitation on a
      newborn, perseverance in reviewing and preparing for delivering the newborn who
      requires ventilation cannot be overlooked, downplayed or pushed to the back of
      the training calendar. All EMS providers, services and systems need to allocate
      time for review and improvement in the knowledge, skills and attitudes required
      to conduct a major resuscitation of a distressed newborn.

PMID- 21736232
TI  - Transition series: topics for the EMT. Part 3: regulation of ventilation,
      ventilation/perfusion ratio and transport of gases.

PMID- 21736233
TI  - Fever in the neonate and young infant: recognizing fever in young infants is
      critical for avoiding potentially serious infections.

PMID- 21736234
TI  - Is it safe? Protocols preach caution, but sometimes a little risk might be
      preferable.

PMID- 21736235
TI  - Women in transplantation: an interview with Patricia Adams, MD.

PMID- 21736236
TI  - Successful follow-up of living organ donors: strategies to make it happen.

PMID- 21736237
TI  - Identifying and addressing barriers to African American and non-African American
      families' discussions about preemptive living related kidney transplantation.
AB  - CONTEXT: Ethnic/racial minority and nonminority families' perceived barriers to
      discussing preemptive living related kidney transplantation (LRKT) and their
      views on the potential value of health care professionals trained to address
      barriers are unknown. OBJECTIVE, SETTING, AND PARTICIPANTS: To collect pilot data
      for evaluating perceived barriers to preemptive LRKT and to inform the
      development of a culturally sensitive intervention to improve families'
      consideration of LRKT. In 4 structured group interviews of African American and
      non-African American patients (2 groups) with progressing chronic kidney disease
      and their family members (2 groups), participants' perceived barriers to
      initiating LRKT discussions and their views regarding the value of social workers
      to support discussions were explored. RESULTS: Patients' barriers included
      concerns about their (1) ability to initiate discussions, (2) discussions being
      misinterpreted as donation requests, (3) potential burdening of family members,
      (4) uncertainty about when to initiate discussions, and (5) inducing guilt or
      coercing family members. Family members' barriers included (1) feeling
      overwhelmed by patients' illness, (2) patients' denial about their illness, (3)
      caregiver stress, and (4) uncertainty about their own health or the health of
      other family members who might donate or need a kidney in the future.
      Participants reported that social workers could facilitate difficult or awkward
      discussions and help families understand the LRKT process, address financial
      concerns, and cope emotionally. Themes were similar between African Americans and
      non-African Americans. CONCLUSIONS: Families identified several barriers to
      discussing preemptive LRKT that could be addressed by social workers. Further
      research must be done to determine whether social workers need to tailor
      interventions to address families' cultural differences.

PMID- 21736238
TI  - Patients' sex and emotional support as predictors of death and clinical
      deterioration in the waiting for a new heart study: results from the 1-year
      follow-up.
AB  - CONTEXT: Little is known about the role of patient's sex and emotional support in
      the prognosis of heart transplant candidates. OBJECTIVE: To examine patient's sex
      and emotional support as predictors of outcomes in the Waiting for a New Heart
      Study. DESIGN, SETTING, AND PARTICIPANTS: The Waiting for a New Heart Study is a
      prospective observational study of 318 patients (18% female) newly added to the
      waiting list for a heart transplant. Demographic, medical, psychosocial
      characteristics (including social support [ENRICHD Social Support Index; high vs.
      low support]) were assessed at the time of wait-listing. Main Outcomes-Time until
      death/delisting due to deteriorated tealth, considering competing outcomes (e.g.,
      transplantation) during the first 12 months after wait-listing were analyzed via
      cause-specific Cox proportional hazard models. RESULTS: By 12 months, 32 men
      (12%) and 10 women (17%) had died/deteriorated. Medical risk was comparable
      across sexes. More men than women reported low emotional support (20.4% vs. 8.6%)
      and being a past or current smoker (80.4% vs. 56.9%). More women than men had low
      vocational level (93.1% vs. 69.6%; all P values < .05). With medical risk and
      other confounding variables controlled for, female sex significantly increased
      risk of death/deterioration (hazard ratio, 2.30; 95% confidence interval, 1.04
      5.12; P = .04); low emotional support further tended to increase the risk for
      this outcome (P = .07). As none of the 5 women with low emotional support had
      reached this end point, analyses were performed in the male sample and revealed
      that men with low emotional support were more than twice as likely to
      die/deteriorate than were men with high support (hazard ratio, 2.23; 95%
      confidence interval, 1.04-4.82; P = .04). CONCLUSION: Women had worse survival
      while awaiting a heart transplant than men had, independent of confounding
      variables. Even though emotional support may be an important buffer for men,
      protective factors for women warrant further investigation with larger samples
      and/or longer follow-ups.

PMID- 21736239
TI  - "It has its ups and downs": adolescents' quality of life after heart
      transplantation.
AB  - CONTEXT: Heart transplantation is not curative and results in a high-morbidity
      chronic illness. Despite this, little research has focused on adolescents'
      quality of life after heart transplant. Such research is critically needed
      because of the complex developmental changes experienced by adolescents and the
      need for transition to self-management during this vulnerable period. OBJECTIVE:
      To examine adolescents' perceptions of their quality of life and factors
      affecting it. DESIGN: Focused ethnography. SETTING AND PARTICIPANTS: Fourteen
      adolescents (mean age, 17 years) who had received a heart transplant at least 6
      months earlier were recruited from a large children's hospital. The ethnically
      diverse sample (7 black, 5 white, 1 Asian, and 1 Hispanic) included 8 females and
      6 males. Data Collection and Analysis-The adolescents participated in audio-taped
      qualitative interviews, which were transcribed verbatim and entered into
      Ethnograph to assist with data management. Thematic analysis was used to identify
      recurrent themes. RESULTS: Participants described life after transplant by
      saying, "It has its ups and downs". Major themes included these: (1) I am normal
      and I am not normal, (2) I am grateful and I am resentful, and (3) I am managing
      and I am not managing. The themes reflect the dichotomous nature of the
      adolescents' experiences and provide insight into the complex needs of
      adolescents after heart transplant.

PMID- 21736240
TI  - Capnocytophagia canimorsus sepsis in an asplenic heart transplant candidate with
      a left ventricular assist system.
AB  - Fulminant septic shock associated with Capnocytophagia canimorsus bacteremia
      developed in a 54-year-old asplenic man, a heart transplantation candidate who
      was supported with a HeartMate II left ventricular assist system, after he
      experienced a dog bite. He improved after administration of broad-spectrum
      antibiotics, which were narrowed to ampicillin/sulbactam for a prolonged 6-week
      course, and subsequently recovered fully.

PMID- 21736241
TI  - Collaborative use of the peer assist model in large transplant programs in the
      United States.
AB  - CONTEXT: The basic assumption of the peer assist model is that nearly every
      transplant center is already doing something that other centers could adopt in
      order to streamline or enhance their own operations. OBJECTIVE: To describe how
      the Transplant Growth and Management Collaborative used the peer assist model
      with 2 large transplant centers in the United States and to identify best
      practices and outcomes. SETTING: The University of California, San Francisco,
      Medical Center. PARTICIPANTS: Transplant health care providers (surgeons, nurse
      transplant coordinators) and administrative staff (program directors, financial
      advisers, quality representatives). INTERVENTION: The peer assist model is a
      mechanism by which a transplant center receives feedback about a specific topic
      from another transplant center that encountered similar issues and developed
      effective action plans for overcoming barriers to success; it is a reciprocal
      model in which knowledge is shared. RESULTS: The peer assist model benefited the
      preparation for accelerated growth in 2 of the largest transplant centers in the
      United States. The collaboration during peer assist visits is an opportune time
      for transplant centers to learn from one another.

PMID- 21736242
TI  - Sleep and daytime sleepiness of patients with left ventricular assist devices: a
      longitudinal pilot study.
AB  - CONTEXT: No empirical longitudinal data on sleep and daytime sleepiness patterns
      in patients with an implantable left ventricular assist device (LVAD) exist.
      OBJECTIVE: (1) To describe the sleep patterns (sleep onset latency, sleep
      efficiency, sleep fragmentation index, total sleep time, and wake after sleep
      onset), sleep quality, and daytime sleepiness variables and (2) to determine the
      change in the pattern of these variables before and up to 6 months after LVAD
      implantation. DESIGN: A longitudinal descriptive repeated-measures design was
      used. Patients wore wrist actigraphs (AW64 Actiwatch), which objectively measured
      sleep, for 3 consecutive days and nights before LVAD implant and at the first and
      second week and first, third, and sixth month after implantation. During these
      periods, patients also completed questionnaires on sleep quality and daytime
      sleepiness. Patients-Twelve of 15 patients completed the 6-month data. Data were
      analyzed by using descriptive statistics and repeated-measures analysis of
      variance. RESULTS: We found long sleep onset latencies and low sleep efficiency
      across time periods. High sleep fragmentation index was noted at baseline and 1
      week after LVAD. Short total sleep times, long wake-after-sleep-onset durations,
      and poor sleep quality were evident at baseline and persisted up to 6 months
      after LVAD implantation. Low alertness level, a manifestation of sleepiness, was
      common during late morning to early evening hours. However, only sleep efficiency
      and wake after sleep onset showed significant changes in pattern (P < .05).
      CONCLUSION: Sleep disturbance and daytime sleepiness may be prevalent before and
      up to 6 months after LVAD implantation, warranting further investigation.

PMID- 21736243
TI  - From insiders' perspectives: adjusting to caregiving for patients with left
      ventricular assist devices.
AB  - CONTEXT: Caregivers for patients with a long-term implantable left ventricular
      assist device have a very important role in helping patients maintain their
      health and well-being and attain an improved quality of life. Although the
      caregiving tasks, burdens, and challenges of family caregivers have been
      described in the literature, we know little about how caregivers adjust to or
      accommodate the new role in their lives. OBJECTIVE: To explore and describe the
      lifestyle adjustments of caregivers for adults living with a left ventricular
      assist device as a bridge to heart transplant or destination therapy. DESIGN: A
      hermeneutic phenomenology was used as a guide for interviews and analysis of the
      data. PARTICIPANTS: A purposive convenience sample of 5 women, aged 39 to 71
      years, who had served as caregivers of a left ventricular assist device patient
      for at least 3 months. SETTING: Recruitment and data collection (interviews) were
      conducted in an outpatient clinic for the mechanical circulatory support program
      of a large academic medical center in the Midwest. RESULTS: Three main themes
      (caregiving: a "24/7" responsibility, coping strategies, and satisfaction) and 13
      subthemes emerged from the data. CONCLUSIONS: Lifestyle adjustments with
      caregiving may become easier over time, and with effective use of coping
      strategies, caregivers accept their new caregiving role as part of life.

PMID- 21736244
TI  - Measurement of cardiac output during adult donor care.
AB  - Measurement of cardiac output may improve hemodynamic management in donor care.
      Selected traditional and more recent methods to quantify cardiac output are
      reviewed. The accuracy or concordance of these newer methods when compared with
      thermodilution techniques that use a pulmonary artery catheter-the current
      reference standard-is discussed. Data directly comparing these systems for
      measuring cardiac output in the donor population are unavailable. However, data
      from groups of hemodynamically unstable patients favor selection of a measurement
      method that permits comparison (calibration) with a reference standard. A
      prospective comparison of all methods against the pulmonary artery catheter
      thermodilution technique among donors would provide the best data to resolve this
      clinical and potentially cost-important question.

PMID- 21736245
TI  - Ventilator autotriggering: a caution in brain death diagnosis.
AB  - The Uniform Determination of Death Act and the American Academy of Neurology's
      Guidelines for Determination of Death define procedures for diagnosis of brain
      death before organ procurement for transplantation, including clinical assessment
      and apnea test. Autotriggering of mechanical ventilators can occur in both brain
      dead and living patients. A case is reported in which procurement was delayed
      because ventilator self-cycling was confused for brainstem-mediated respiratory
      effort. Background knowledge to effectively troubleshoot ventilator self-cycling
      is offered so that unnecessary delays in brain death testing can be avoided.

PMID- 21736246
TI  - Donation after cardiac death for lung transplant: a case study.
AB  - In late 2009, Gift of Life Michigan facilitated a donation after cardiac death
      lung recovery resulting in the first set of donation after cardiac death lungs to
      be utilized by a Michigan transplant center. Although placing lungs obtained via
      donation after cardiac death is more difficult because of a multitude of factors,
      the transplant coordinators, in conjunction with the transplant center, overcame
      several obstacles in order to transplant the lungs with good outcomes so far.
      Lung donation after cardiac death is becoming a more acceptable method of
      decreasing the length of the transplant waiting list as more data are becoming
      available.

PMID- 21736247
TI  - Religious and ethnic influences on willingness to donate organs and donor
      behavior: an Australian perspective.
AB  - CONTEXT: Globally, the demand for donated organs outstrips supply, meaning that
      there are both practical and theoretical reasons for examining factors that are
      predictive of individuals' willingness to donate their organs upon their death.
      OBJECTIVES: To determine whether individuals of different religious denominations
      living in Australia have different views on organ donation, whether donation
      attitudes differ significantly across ethnic groups, and whether factors
      identified in international research are predictors of willingness to donate and
      actual donor behavior in this population. PARTICIPANTS: Data for this study were
      collected from students at an Australian university from a range of religious and
      ethnic backgrounds, and their friends and relatives (N = 509). Intervention
      Participants were administered the Organ Donation Attitude Scale, as well as
      additional attitudes and knowledge measures. MAIN OUTCOME MEASURES: Self-reported
      "willingness to donate" and "donor behavior". RESULTS: Our findings complemented
      those reported in comparable countries, with females, younger Australians, and
      those with high knowledge levels being more willing to donate than males, older
      persons, and those with low knowledge. Persons who described themselves as having
      stronger religious beliefs (particularly Buddhist and Islamic) held less
      favorable attitudes toward donation, had lower knowledge levels, and were more
      likely to oppose donation. CONCLUSIONS: Although this study established that
      attitudes toward, knowledge about, and predictors of organ donation in Australia
      are similar to those reported elsewhere, donation rates remain low. Further in
      depth research examining the impact of religion and culture on attitudes,
      beliefs, and behavior is essential when exploring strategies to improve organ
      donation rates in highly multicultural societies such as Australia.

PMID- 21736248
TI  - Transplant cost-report tracking at Henry Ford Transplant Institute and other
      centers nationwide.
AB  - CONTEXT: The lack of uniformity in the reporting of direct and indirect costs by
      organ acquisition cost centers, diagnosis-related groups, and in physician
      reimbursement often results in Medicare overpayment and findings of unjustified
      charges in audits conducted by the Office of the Inspector General. Although it
      is true that organ transplantation costs vary widely, uniform cost-report
      accounting is needed. OBJECTIVE: Henry Ford Transplant Institute has developed
      systematic auditing protocols that result in acceptable compliance with Medicare.
      The differences between those protocols and the methods used elsewhere are
      illustrated by the results of a national survey of transplant centers. DESIGN:
      The survey addresses 10 crucial questions, drawn from the cost-reporting model
      used at Henry Ford Transplant Institute. Setting-Surveys were distributed via the
      United Network for Organ Sharing listserv, with replies from 43 centers. PATIENTS
      OR OTHER PARTICIPANTS: The participants were transplant administrators. RESULTS:
      Several important practices that are audited by the Office of the Inspector
      General were not followed by a number of reporting institutions. About 30% did
      not account for pretransplant charges, 15% did not track pretransplant services,
      40% do not use an external consultant, and the frequency of physician time
      studies varied. On the other hand, the vast majority of institutions perform
      frequent time studies and manually review pretransplant charges. These results
      suggest that most centers use accounting methods similar to those used at Henry
      Ford Transplant Institute, which will significantly improve recognition of
      pretransplantation costs.

PMID- 21736249
TI  - Educating nurses about research ethics and practices with a self-directed
      practice-based learning program.
AB  - Learner-driven and practice-based education programs are recommended for
      integration of learning. A continuing education program on research ethics was
      introduced to five nurses in an ambulatory care setting at a Magnet(r) hospital,
      using a commercially available web-based course followed by a research practicum.
      The seasoned nurses reported little previous education in this area. Working with
      a nurse researcher, three nurses participated in a research project for improving
      clinic care delivery. The success of the continuing education program was
      determined by knowledge acquisition, satisfaction with learning activities, and
      perceived confidence in research participation. This continuing education program
      was effective in providing for knowledge and skill development in research
      ethics. The integrative learning format was well received.

PMID- 21736250
TI  - Enhancing medical-surgical nursing practice: using practice tests and clinical
      examples to promote active learning and program evaluation.
AB  - In a 14-week medical-surgical nursing review course, two teaching strategies are
      used to promote active learning and assess the transfer of knowledge to nursing
      practice. Practice tests and clinical examples provide opportunities for
      participants to engage in self-assessment and reflective learning and enhance
      their nursing knowledge, skills, and practice. These strategies also contribute
      to program evaluation and are adaptable to a variety of course formats, including
      traditional classroom, web conference, and online self-study.

PMID- 21736251
TI  - Kids who travel.

PMID- 21736252
TI  - This issue: travel medicine.

PMID- 21736253
TI  - A 9-month-old boy with a 3-week history of fever.

PMID- 21736254
TI  - 30 years of pediatric HIV/AIDS treatment: a time of breakthroughs, innovation.

PMID- 21736255
TI  - A 6-year-old boy with shoulder pain. Splenic abscess.

PMID- 21736256
TI  - Immunization for pediatric international travelers.

PMID- 21736257
TI  - Enteric vaccines for resource-limited countries: current status and future
      prospects.

PMID- 21736258
TI  - Health implications of adolescent travel.

PMID- 21736259
TI  - Infections, dermatologic conditions in the returned pediatric traveler.

PMID- 21736260
TI  - Travel clinics in pediatric and adolescent travel.

PMID- 21736261
TI  - Medical work in developing countries: how to approach a global health experience.

PMID- 21736262
TI  - The use of aerobiological data on agronomical studies.
AB  - Pollination is only one of the many events comprising the plant development
      cycle; however, it is extremely important for yield where seed is required.
      Although successful fertilization depends on a number of environmental and
      endogenous factors, including climate and plant nutritional status, a sufficient
      quantity of pollen must reach the receptive stigma in order to enhance
      fertilization potential. Aerobiological research focuses on the airborne
      dispersal of biological particles, including pollen grains from anemophilous
      plants. Airborne pollen data are currently used for various purposes in
      agricultural research. One major use is as a source of advance information
      concerning variations in the final fruit harvest of wind-pollinated species. This
      application, first introduced in the field of plant pathology in the 1940s, was
      further developed in the 1970s in French studies of vineyard yield; more
      recently, it has been successfully tested both in crops and in non-crop forest
      species such as oak or birch. Nowadays, aerobiological research into the
      influence of pollen emission on final fruit production takes into account a
      number of other variables, including weather-related factors and
      phytopathological data; it also uses new, computerized statistical tools to
      obtain more precise information on agricultural yield and phytopathological
      risks.

PMID- 21736263
TI  - A possible role of chitin in the pathogenesis of asthma and allergy.
AB  - Chitin is the second most abundant polysaccharide in the world; it is found in
      insects, parasites and fungi. Chitinases break down chitin, and are a part of the
      defence mechanism against chitin-containing parasites in lower life forms. This
      review is based on the results of PubMed-searches using the search-terms: chitin,
      chitinase, allergy and asthma. Research in murine models has proved that chitin
      is a size-dependent microbial-associated molecular pattern, with the ability to
      induce an immunological response via pattern recognition receptors. Medium-sized
      chitin micro-particles (CMPs) have been shown to induce inflammation, while small
      sized CMPs reduce inflammation. The amount of acidic mammalian chitinase
      correlates with asthma, and the enzyme has been shown to induce chemokine
      secretion in murine lungs. The high prevalence of asthma among people working
      with chitinous substances, such as crabs and fungi, supports the hypothesis that
      chitin might be an allergen playing a role of significance in the development of
      asthma. This new knowledge about chitin and chitinases, combined with the hygiene
      hypothesis, may contribute to a model for the pathogenesis of allergic conditions
      where chitin and chitinases are potential therapeutic targets.

PMID- 21736264
TI  - Mite allergy and mite exposure in Iceland.
AB  - In this overview of investigations into mite allergy in Iceland and of the
      current understanding of the sources of exposure, 2 major categories of mite
      induced allergies were encountered. The first was house dust mite allergy due to
      house dust mites from unknown sources, and the second was barn allergy caused by
      mites connected with the degradation of stored hay. Characteristics of these
      diseases have been obtained from surveys where skin prick tests were made with
      commercially available extracts of mites and from zoological investigations where
      mites had been found in different kinds of dusts relevant for the tested persons.
      The investigations uncovered a discrepancy between the capital Reykjavik and
      countryside farms. While the frequencies of sensitization to house dust mites and
      barn mites are rather similar in the capital area and in the rural area, the
      exposure to these mites is unexpectedly low in the capital area. Thus,
      sensitization appears to take place preferably in the rural area.

PMID- 21736265
TI  - Exposure to bioaerosols in the selected agricultural facilities of the Ukraine
      and Poland - a review.
AB  - The aim of this work was to review the studies on bioaerosols which were carried
      out in the years 1972-2009 in following branches of agricultural industry in the
      Ukraine and Poland: animal farms for cows and pigs, animal feed facilities,
      production of biofuel from rape, herb farms and herb processing facilities. In
      all facilities were determined: concentration of dust and microorganisms in the
      air and species composition of microflora. Moreover, in Polish animal farms, herb
      farms and herb processing facilities, as well as in the Ukrainian animal feed
      facilities, was determined the concentration of bacterial endotoxin in the air.
      Dust concentrations in animal farms located in the Ukraine and Poland ranged from
      6-200 mg/m(3) and from 0.25-14.05 mg/m(3), respectively, while in animal feed
      facilities they ranged from 35-306 mg/m(3) and from 3.8-405 mg/m(3),
      respectively. Dust concentrations in the facilities producing biofuel from rape
      in the Ukraine were in the range 3.6-28 mg/m(3), whereas on herb farms and in
      herb processing facilities in Poland they were in the range 0.8- 1,319.6 mg/m(3),
      and 2.2-946 mg/m(3), respectively. The determined values exceeded in most cases
      the maximal acceptable concentration (MAC) which in the Ukraine and Poland is
      equal to 4 mg/m(3). The concentrations of microorganisms on animal farms located
      in the Ukraine and Poland ranged from 5.5 x 10(4)- 1.9 x 10(7) cfu/m(3) and from
      4.7 x 10(4)-1.5 x 10(6) cfu/m(3), respectively, while in animal feed facilities
      they ranged from 2.7 x 10(4)-2.6 x 10(9) cfu/m(3) and from 1.7 x 10(3)-2.0 x
      10(6) cfu/m(3), respectively. Concentrations of microorganisms in the facilities
      producing biofuel from rape in the Ukraine were in the range 1.5 x 10(3)-5.7 x
      10(6) cfu/m(3), whereas on herb farms and in herb processing facilities in Poland
      they were in the ranges of 8.8 x 10(2)-8.0 x 10(6) cfu/m(3), and 9.7 x 10(3)-6.3
      x 10(5) cfu/m(3), respectively. The determined values exceeded in most cases the
      maximal acceptable concentration (MAC) which in the Ukraine is equal to 5.0 x
      10(4) cfu/m(3). The concentrations of endotoxin in Polish animal houses were in
      the range 0.00125-75.0 ug/m(3), whereas on herb farms and herb processing
      facilities they were in the ranges of 0.0045- 2,448.8 ug/m(3) and 0.2-681.0
      ug/m(3), respectively, and in the Ukrainian animal feed facilities were within
      the range 0.008-240.0 ug/m(3). They exceeded in most cases the level of 0.2
      ug/m(3) proposed as a threshold. In the air microflora of examined facilities
      prevailed Gram-positive bacteria (corynebacteria, cocci, spore-forming bacilli,
      actinomycetes) of which some (Arthrobacter spp., thermophilic actinomycetes)
      could be a cause of allergic alveolitis (hypersensitivity pneumonitis). Among
      Gram-negative bacteria isolated from the air of agricultural settings dominated
      the epiphytic species Pantoea agglomerans, possessing potent allergenic and
      endotoxic properties. Fungi were abundant in the air of the Ukrainian
      agricultural settings and comprised species able to produce harmful mycotoxins.
      In conclusion, the airborne biological factors in stated concentrations may exert
      harmful effects on the state of the health of exposed workers. Formation of the
      bioaerosol depends on the specificity of the setting, kind of technological
      operations, degree of mechanization, properties of processed materials,
      temperature and humidity, and concentration of dust in the air.

PMID- 21736266
TI  - The impact of economic factors on the realities of outpatient multi-drug
      treatment of chronic diseases in rural areas.
AB  - The reform of the health care system in Poland introduced in 1999 brought not ony
      a lot of disappointments arising from the failure in performing its basic
      assumptions, but also from the deterioration in access to medical care by
      patients coming from the poorest class of the Polish population. The subjects
      were 209 people at the age of 52-80 years including 149 women and 60 men -
      inhabitants of rural areas of Lublin province. These were outpatients who
      attended the Endocrine Clinic in Poniatowa. The studies were conducted with the
      use of the standardized survey questionnaire. Of all 209 respondents requiring
      long-term multidrug therapies for chronic diseases, 128 (61.2% of those surveyed)
      reported episodic or permanent noncompliance to treatment regimens, 90 people
      (43%) had applied medications in a way at variance with medical recommendations.
      Among the reasons, economic factors were most often mentioned. Ony 21 respondents
      (10%) expressed the opinion that they had always possessed sufficient means to
      buy necessary drugs. Current regulations concerning the refunding of costs of
      medicines may make effective outpatient treatment of chronic diseases impossible.
      Almost 61.2% of the polled treated themselves contrary to medical
      recommendations. In most cases, improper courses of treatment were caused by
      financial problems.

PMID- 21736267
TI  - Course of occupational asthma depending on the duration of workplace exposure to
      allergens - a retrospective cohort study in bakers and farmers.
AB  - The management of occupational asthma requires valid information about prognostic
      factors. The present study therefore investigates the importance of exposure
      duration, work cessation, and confounding factors on allergic obstructive airway
      disease in bakers and farmers. Patients with confirmed allergic occupational
      airway disease registered in a German Occupational Health Inspectorate received a
      mailed questionnaire on their respiratory health and employment status. Relations
      between duration of exposure and course of disease were analysed by
      multifactorial logistic regression under consideration of confounding variables.
      178 patients (65 [36.5%] farmers and 113 [63.5%] bakers) aged between 24 and 74
      (mean 42.0 +/- standard deviation 12.7) years of age were included in the
      analysis. Farmers had much more severe respiratory complaints than bakers, and a
      significantly larger proportion of them (77.5%) had been employed for over 10
      years (bakers: 36.6%). Unlike in bakers (Odds-Ratio for a sum score of more than
      4 points 6.48 [95%CI 2.04-20.56]), among farmers (OR 1.47 [95%CI 0.30-7.29]) the
      duration of work under exposure did not independently explain the severity of
      respiratory complaints. The multivariate statistical analysis confirms the
      prognostic value of the cessation of work in occupational asthma; this remedy,
      however, is often not available for farmers.

PMID- 21736268
TI  - Effect of lambda-cyhalothrin on memory and movement in mice after transient
      incomplete cerebral ischemia.
AB  - Lambda-cyhalothrin (LCH) is a synthetic pyrethroid used as an insecticide. The
      aim of the study was to investigate the effect of LCH on memory, movement
      activity, and co-ordination in mice exposed to bilateral clamping of the carotid
      arteries (BCCA). On the first postsurgical day, the examined animals (BCCA/LCH)
      were injected with LCH i.p. and trained in the passive avoidance task 30 min.
      after the injection. Controls were: sham-operated animals (SHAM), with their
      carotids exposed but not occluded, animals subjected to BCCA (BCCA), and sham
      operated mice injected with LCH (SHAM/ LCH). In the following experiments, memory
      retention, working spatial memory, movement activity, and co-ordination were
      examined. Neither memory nor movement co-ordination were impaired by BCCA or LCH.
      Exploratory locomotor activity was significantly reduced in the BCCA/LCH group (p
      < 0.01 vs SHAM). Spontaneous movement activity was significantly reduced in the
      BCCA/LCH group (p < 0.001 vs SHAM, p < 0.05 vs BCCA, p < 0.001 vs SHAM/LCH), as
      well as in the BCCA group (p < 0.01 vs SHAM). Exposure to LCH coexisting with
      BCCA decreased motor activity in the mice in 2 subsequent 30-min. periods of
      observation. BCCA itself decreased motor activity in the 31-60 min. of
      observation. These results show that BCCA combined with exposure to a subtoxic
      dose of LCH does not impair memory; however, they affect behaviour by reducing
      the horizontal movement activity in mice.

PMID- 21736269
TI  - Potential association between Coxiella burnetii seroprevalence and selected risk
      factors among veterinary students in Slovakia.
AB  - The present study investigated the prevalence of antibodies to Coxiella burnetii
      and the possible factors predisposing students of veterinary medicine to C.
      burnetii infections. IgG antibodies to phase I and phase II C. burnetii antigens
      were determined by ELISA. Out of 77 students examined, 13 were positive for phase
      I and 45 were positive for phase II antibodies. The titres determined were in the
      range of 1 : 100-1 : 3200. Some risk factors may have contributed to the high
      seroprevalence found in these subjects. For example, there were positive
      associations with rural life and exposure to the breeding of farm animals, and in
      addition, work in a dusty environment, such as on fields, gardens, stables and
      construction sites were also connected to high seroprevalence.

PMID- 21736270
TI  - Effect of repetitive mowing on common ragweed (Ambrosia artemisiifolia L.) pollen
      and seed production.
AB  - Ambrosia artemisiifolia L (common ragweed) is a familiar roadside weed in
      southern Quebec (Canada) that produces large amounts of airborne pollen
      responsible for multiple rhino-conjunctivitis (hay fever) cases. As roadside
      weeds are increasingly controlled by mowing alone, the effect of a mowing
      treatment on pollen production was evaluated. Ambrosia artemisiifolia plants were
      grown in a greenhouse at 4 densities (1, 3, 6 and 12 plants per 314 cm(2) pot)
      and either left intact or mowed (10 cm from the ground) when the plants reached
      25 cm in height, i.e. twice during the life cycle of this annual plant. Pollen
      production per male inflorescence was collected in open-top bags and counted.
      Inflorescence mass, length, location on the plant and date of anthesis onset was
      noted. Above-ground plant biomass and seed production was also evaluated. Mowed
      plants produced less pollen per unit of inflorescence length than intact plants.
      Pollen production per plant was reduced by a factor of 8.84 by the double mowing
      treatment, while viable seed production per plant was reduced by a factor of
      4.66, irrespective of density. Mowing twice has the potential to reduce airborne
      pollen loads but Ambrosia artemisiifolia seed banks are unlikely to be depleted
      by this management strategy.

PMID- 21736271
TI  - Microbial air quality at Szczawnica sanatorium, Poland.
AB  - Nowadays, sanatorium treatment is undergoing a renaissance; however, data on air
      quality in such premises are scarce. The aim of this study was to characterize
      microbial air quality at the Szczawnica sanatorium in Southern Poland. The
      bioaerosol measurements were carried out using a 6-stage Andersen impactor over a
      period of one year in 3 naturally ventilated sanatorium premises (where different
      curative treatments took place) and in outdoor air. The indoor and outdoor
      concentrations of fungal aerosol were always below 1,600 cfu/m(3). With regard to
      bacterial contamination, the highest concentrations (up to 6,223 cfu/m(3)) were
      usually noted when the patients were present and underwent curative procedures.
      Such concentrations crossed the Polish threshold limit values, which suggest that
      natural ventilation in this type of premises did not ensure the proper air
      quality; therefore a high-performance ventilation or air-conditioning system
      should be introduced to provide the "clean" air into the curative treatment
      rooms. Qualitative evaluation of bioaerosols revealed that the most prevalent
      indoors were Gram-positive cocci, mesophilic actinomycetes, and filamentous
      fungi. Analysis of microclimate parameters confirmed that ony relative humidity
      of the air influenced significantly the levels and composition of microbial
      aerosols. Hence, the constant control of this parameter should be scrupulously
      supervised at sanatorium premises.

PMID- 21736272
TI  - Work-related musculoskeletal disorders among dentists - a questionnaire survey.
AB  - Dentists at work are susceptible to the development of health disorders. Bad
      working habits, repetitive tasks and uncomfortable posture contribute to
      musculoskeletal disorders (MSDs), stress and loss of production. The paper deals
      with the assessment of health status among dentists in Poland regarding the
      symptoms of musculoskeletal pain. The survey was conducted among 220 dentists.
      The questionnaire was concerned with demographic details, work duration and
      acquired specialization, organization and methods of work in the surgery, and
      also disorders connected with the musculoskeletal system and physical
      prophylactic activity. It was found that over 92% of the surveyed dentists
      experienced MSDs, especially in the neck (47%) and lower back (35%). More than
      29% of the dentists experienced trouble with fingers, 23% with hip, whereas 20%
      demonstrated problems in the midback, and also in the shoulders (20%). Pain in
      the wrists was reported by 18.3%, and pain in the knees, feet or elbows by 15-16%
      of respondents. Statistical dependence was shown between the years of practice
      and the period of time when disorders occurred. Moreover, significance
      relationships were found between MSDs and both standing work position and non-use
      of rest breaks. It was concluded that limited ergonomics in the work environment
      of dentists results in MSDs, and its prevalence is very high. The symptoms of
      MSDs increased with the number of years of practice.

PMID- 21736273
TI  - Content of transfluthrin in indoor air during the use of electro-vaporizers.
AB  - The quality of indoor air evokes increasing interest; however, no standards have
      been developed which determine the content of pesticides in the air of living
      space. At present, insecticides are increasingly more frequently applied to
      control household pests, flies, mosquitoes, termites and other harmful insects.
      In this study, the content of transfluthrin was measured indoors after the
      application of two consumer products containing this active substance, using
      commercially available electro-vaporizers. It was found that during the
      application of insecticides in the form of gel and liquid the mean concentration
      of transfluthrin in the air was 1.295-2.422 ug/m(3) and 3.817-5.227 ug/m(3),
      respectively. The concentration of an active agent in the air did not depend on
      the day of application. The concentration of transfluthrin was higher when used
      in the form of a liquid than a gel preparation. 18-24 hours after the
      discontinuation of the use of the preparation no active agent was found in the
      air. As long as the standards are developed regulating the content of
      insecticides in the air of living spaces and utility rooms, the most important
      method of preventing their potential hazardous effect is informing the users of
      these preparations about the occurrence of active substances in indoor air, and
      eventual risk of exposure to the effect of pesticides during their application at
      home.

PMID- 21736274
TI  - Concentration of fungal biomass and trichothecenes in different parts of einkorn.
AB  - Analyses of ergosterol (ERG), adenosine-5'-triphosphate (ATP) and groups A and B
      trichothecenes were performed in three Triticum monococcum cultivars registered
      in Germany (Albini, Terzino and Tifi), grown in the organic system. The
      experiment was carried out on two dates: the first - in the final phase of
      flowering (BBCH 69) and the second -- in the phase of full ripeness (BBCH 89).
      The analyses were performed on shanks, glumes, grain and awns. Concentrations of
      analyzed metabolites in different parts of T. monococcum plants varied
      significantly. Mean ERG concentration in the first term was more than 30 times
      higher than immediately before harvest, whereas for group B trichothecenes it was
      4 times higher. Contents of ATP and concentrations of group A trichothecenes were
      similar at both times. When analyzing parts of the spike, the highest amount of
      metabolites was recorded in shanks (ERG - 114 mg/kg, ATP 900,000 RLU, group A and
      B trichothecenes - 0.07 and 0.20 mg/kg, respectively), while the lowest in grain
      (ERG - 5 mg/kg, ATP 55,000 RLU, group A and B trichothecenes - 0.03 and 0.08
      mg/kg, respectively). A higher ERG concentration was found in awns (65 mg/kg)
      than in glumes (41 mg/kg), whereas for ATP and group A and B trichothecenes by
      contrast higher concentrations were recorded in glumes (160,000 RLU, 0.06 and
      0.029 mg/kg, respectively) than in awns (77,000 RLU, 0.05 and 0.014 mg/kg,
      respectively). Recorded results indicate a potential occurrence of trichothecenes
      in shanks, awns and glumes already during flowering, when grain has not yet
      developed. In these parts of plants, after harvest, the highest amounts of
      microorganisms and Fusarium toxins were found, which pose a threat for farmers
      and workers employed in the cereal industry.

PMID- 21736275
TI  - Aerobiological study in east-central Iberian Peninsula: pollen diversity and
      dynamics for major taxa.
AB  - A study was made of airborne pollen counts in Cuenca (east-central Iberian
      Peninsula, Spain), using data obtained over a 3-year period (2008-2010). This is
      the first such study carried out in the World Heritage city of Cuenca, situated
      in the large region of Castilla-La Mancha. Air monitoring was performed using the
      sampling and analysis procedures recommended by the Spanish Aerobiology Network.
      Sampling commenced in mid- 2007, and provided the first recorded pollen-spectrum
      for the area. The greatest pollen-type diversity was recorded in spring, whilst
      the highest pollen counts (over 80 percent of the annual total) were observed
      between February and June. The lowest counts were found in September, November
      and December. The 10 leading taxa, in order of abundance, were: Cupressaceae,
      Quercus, Urticaceae, Pinus, Olea, Poaceae, Populus, Platanus, Chenopodiaceae
      Amaranthaceae and Plantago. The pollen calendar was thus typically Mediterrean,
      and comprised the 27 pollen types reaching 10-day mean counts of over 1
      grain/m(3) of air. Maximum concentration values during the day were recorded
      between 12:00-20:00, coinciding with the highest temperatures and lowest humidity
      levels. The pollen types responsible for most allergies in the city of Cuenca,
      ordered by the number of days on which risk levels were reached, were: Poaceae,
      Urticaceae, Cupressaceae, Olea, Platanus and Chenopodiaceae-Amaranthaceae.

PMID- 21736276
TI  - Environmental conditioning of incidence of tick-borne encephalitis in the south
      eastern Poland in 1996-2006.
AB  - Epidemiological studies of tick-borne encephalitis (TBE) conducted in the
      Swietokrzyskie province (south- eastern Poland) in 1996-2006 demonstrated an
      increase in the number of registered TBE cases in the last 6 years of the study.
      The highest risk of TBE virus infections occurs in the summer-autumn period
      (seasonality factors 96.55% and 248.28%), i.e. in periods of the highest Ixodes
      ricinus activity in this region. An increased number of registered TBE cases were
      noted in the regions which provide ticks with favourable habitats and,
      simultaneously, where the TBE diagnosis and treatment for the inhabitants are
      more efficient. The increasing tendency in TBE incidence observed even in the non
      endemic regions of the Swietokrzyskie province indicates the necessity of
      education in tick-borne disease prophylaxis and the need to elevate the level of
      public health care. Differences in the density and activity of various
      developmental Ixodes ricinus stages were observed in 4 localities in diverse
      biotopes located at different altitudes a.s.l. This justifies the necessity of
      environmental monitoring of the threats posed by ticks in various habitats,
      especially in those frequently visited by humans.

PMID- 21736277
TI  - Meteorological parameters and severity of acute pulmonary embolism episodes.
AB  - Frequency of acute pulmonary embolism episodes has been previously shown to
      correlate significantly with meteorological factors in the period preceding their
      occurrence. The purpose of the study was to analyze the relation of
      meteorological factors and the severity of acute pulmonary embolism, expressed by
      the CT-based pulmonary obstruction score. A retrospective analysis of medical
      data of 182 consecutive patients with acute pulmonary embolism diagnosed with CT
      pulmonary angiography was performed. Severity of pulmonary obstruction was
      assessed by analysis of CT pulmonary angiography examinations, and defined with
      pulmonary obstruction score by Qanadli et al. The study group was divided into
      low (L group, 95 patients) and high PE severity (H group, 87 patients), with a
      cutoff value of 50% of maximum pulmonary obstruction score. Meteorological data
      collected for the relevant time period were: air temperature, humidity,
      atmospheric pressure, visibility, wind speed and precipitation. No significant
      differences in seasonal distribution of pulmonary embolism episodes were
      observed. Episodes of more severe pulmonary embolism were preceded by periods of
      lower atmospheric pressure (1,016.35 hPA for group H, vs. 1,016.35 hPa for group
      L, p = 0.022). No significant relations between other meteorological factors and
      severity of PE were observed. The reported finding shows the need of further
      research on the nature of meteorological factors influence on the course of
      pulmonary embolism, which should be analyzed not ony regarding the frequency, but
      also severity of PE episodes.

PMID- 21736278
TI  - Lyme borreliosis in south-eastern Poland: relationships with environmental
      factors and medical attention standards.
AB  - Yhe aim of the study was the investigation of the dynamics of LB prevalence in
      central Europe over a 12-year period and estimation of its dependence on the
      environmental factors and on the level of medical services. Epidemiological
      studies of LB were conducted in the years 1996-2007 in 9 regions of the
      Swietokrzyskie province in south-eastern Poland (Central Europe). On the basis of
      patient registry, the incidence, prevalence in various months of the year, the
      mean number of cases in various seasons and the seasonality factors (SF) of LB
      were calculated. Between 2000-2007, an increased borreliosis incidence was
      observed in the study area. During the entire study period, the highest incidence
      (25.93 and 30.66) was observed in the regions with the highest density of Ixodes
      ricinus ticks - vectors of Borrelia burgdorferi spirochetes, and where the
      inhabitants are offered the best available LB diagnosis and treatment due to a
      sufficient number of doctors (r = 0.74) and all medical personnel (doctors,
      nurses and diagnosticians) (r = 0.89). The highest LB incidence was present in
      the summer and autumn seasons (SF = 113.25 and 155.18%) in the areas with the
      highest density of nymphs and adult I. ricinus ticks (> =19/1 h of sampling).
      Improved standards of public medical care as well as environmental monitoring of
      tick threat may contribute to a decrease in prevalence of LB and to its better
      detection.

PMID- 21736279
TI  - Proliferation of cells and expression of RARs, RXRs and HPV viral E6 and E7
      proteins in cervical cancer cell lines after treatment with ATRA.
AB  - All-trans retinoic acid (ATRA) is considered to be a potential chemotherapeutic
      drug due to its capability to regulate cell growth and differentiation. The
      effects of ATRA on the proliferation of cells and gene regulation are mediated by
      retinoid receptors (RAR and RXR), which belong to the nuclear receptor
      superfamily of ligand- inducible transcription factors. ATRA can act either as a
      growth inhibitor or growth promoter, according to the functional state of
      retinoic receptors. Thus, we have established the effect of ATRA on the
      proliferation of cervical cancer cells line HeLa and CaSki and expression of
      retinoids receptors as well as the viral HPV oncogenic proteins E6 and E7. ATRA
      had no effect on proliferation CaSki cells, but it stimulated the growth of HeLa
      cells, which depended on the incubation time and the concentration of ATRA in
      cell culture. The overexpression of RAR alpha in HeLa cells after the
      administration of 10(-7) mM ATRA was also observed 72 hours, and the decrease of
      CaSki by 60-90%. In the study of cervical cancer cell lines, the very low levels
      of other endogenous RAR and RXR receptors were observed. ATRA does not repress
      the expression of two viral oncoproteins E6 and E7 HPV16/18, which play a key
      role in carcinogenesis of the cervix. Our results support the suggestions that
      the cell response to vitamin A, and other retinoids in the diet, may depend on
      cell type, and that the cancer cells are differentially resistant to retinoids.
      Thus, despite the important biological functions of retinoids, the effects of
      retinoids in a supplementation in supra-physiological doses as well as their
      physiological action are difficult to define.

PMID- 21736280
TI  - Tick bites on humans in the agricultural and recreational areas in south-eastern
      Poland.
AB  - The investigations were conducted in the Lublin province (south-eastern Poland)
      in areas of high agricultural and recreational value. Among the 418 patients
      admitted to medical clinics due to arthropod bites in the years 2003-2005, 184
      people (44%) had been bitten by ticks. As shown by the research, high-risk groups
      include people whose stay in tick habitats is connected with their occupational
      work (54.5%) as well as recreation and tourism (45.5%). As many as 78.7% of the
      patients were attacked by Ixodes ricinus ticks in forests, and much fewer (31.3%)
      in other habitats located in urban and rural areas. In one case, a Dermacentor
      reticulatus female was attached to the skin. Ticks were most commonly located on
      the upper (28.8%) and lower (27.2%) extremities, and on the abdomen (15.8%).
      Local skin reactions (57.6%) with predominance of erythema were the most
      prevalent. Combined local and systemic symptoms were reported less frequently
      (20.1%). The general symptoms were headache (10.8% of patients), fever (5.4%),
      lymphadenitis (5.9%) and arthralgia (4.3%). No lesions produced by tick bites
      were reported in 22.3% of the patients. Field studies conducted in 2003-2004
      demonstrated that I. ricinus is a common species in the southern part of the
      Lublin province, where the density of nymphs and adult forms in various
      localities during the period of peak seasonal activity (in May) ranges from 18.5
      26 specimens/1 h of collection. Two tick species, I. ricinus and D. reticulatus,
      occur in the northern part of the province. The density of I. ricinus nymphs and
      adult forms as well as D. reticulatus adults is in the range of 2.5-42
      specimens/1 hr of collection and 19.5-64.0 speciments/1 hr of collection,
      respectively. Due to the high risk of tick attacks in the study area, there
      arises the necessity to permanent the monitoring of ticks numbers and tick-borne
      diseases.

PMID- 21736281
TI  - Mouse model of hypersensitivity pneumonitis after inhalation exposure to
      different microbial antigens associated with organic dusts.
AB  - The aim of this study was to reproduce in laboratory conditions hypersensitivity
      pneumonitis (HP) pathogenesis in a new animal model predictive of the human
      response, and to select the microbial antigen associated with organic dust that
      exerts the strongest pathogenic effect on the respiratory organ. To achieve this
      goal, mice of the strain C57BL/6J prone to fibrosis were exposed for 1 hour daily
      up to 28 days to the inhalation of aerosols of each of the 5 microbial components
      of organic dusts whose conjunction with the occurrence of HP has been confirmed
      by numerous authors: Pantoea agglomerans saline extract (SE), P. agglomerans
      microvesicle-bound endotoxin, Saccharopolyspora rectivirgula SE, Aspergillus
      fumigatus SE, saline extract of dust from a grain sample overgrown with S.
      rectivirgula and Thermoactinomyces vulgaris, and a saline solvent (PBS) was used
      as a control. Exposure of the animals to organic dust components was conducted
      using a novel inhalation challenge set. Lung samples were collected from
      untreated mice and from mice exposed for 7 and 28 days, and examined by
      digitalized histopathology and biochemistry for the presence of inflammatory
      changes and fibrosis. P. agglomerans SE appeared to be the sole antigen which
      evoked a statistically significant fibrosis and a significant increase of
      hydroxyproline in the lungs of mice exposed for 28 days to this extract, both
      compared to the mice untreated and to those exposed to the solvent. P.
      agglomerans SE also evoked the strongest and statistically significant
      inflammatory response in the lungs of the mice, both after 7 and 28 days of
      exposure. After 7 days, significant inflammatory changes were also found in mice
      exposed to A. fumigatus SE, and after 28 days in mice exposed to all antigens. In
      conclusion, our results allow us to define a useful animal model of HP which can
      be a supplement for now commonly used bleomycin model. This model should
      comprise: present set of instruments for inhalation, mice of the line C57BL/6J
      and the saline extract of P. agglomerans as the antigen. For a better
      understanding of the presented results, a detailed study covering immunological
      investigations, focused on the mechanism of antigen action, are needed.

PMID- 21736282
TI  - Nutritional behaviours among pregnant women from rural and urban environments in
      Poland.
AB  - Based on data obtained from the system MoZMaD - PL (Polish Mother and Child
      Health Monitoring System); an equivalent of the American system PRAMS (Pregnancy
      Risk Assessment Monitoring System). The health behaviour of a pregnant woman,
      including adequate nutritional behaviours and supply of all the necessary
      nutrients, exert an effect on the health of a woman, development of the foetus,
      and the occurrence of diseases among the offspring at the age of maturity. The
      objective of the study was analysis of the nutritional behaviours among Polish
      pregnant women, with particular consideration of the recognition of dietary
      changes caused by the fact of becoming pregnant. The studies were based on
      questionnaire forms within the Polish Mother and Child Heath Monitoring System
      (MoZMaD - PL) implemented in Poland. The precise day of studies is appointed
      annually for the whole of Poland by the Chief Sanitary Inspector. The
      questionnaire forms were correctly completed in 2010 by 2,877 women. The replies
      to the questions were introduced by surveyors into the MoZMaD - PL system, a
      central database managed by the Institute of Agricultural Medicine. The results
      obtained were subjected to statistical analysis. More than a half of Polish women
      change their diet in pregnancy. According to the pregnant women examined, the
      changes in their diet consist in a more frequent consumption of white meat, fish,
      fruits and vegetables, as well as milk and dairy products. Favourable changes in
      diet were observed primarily among the respondents from the urban environment.
      Considering an insufficient awareness with respect to nutritional behaviours
      among females at reproductive age, the education of pregnant women and those who
      plan a pregnancy concerning an adequate diet should be jointly conducted by
      medical circles, schools, and the media, and directed primarily to women from the
      rural environment.

PMID- 21736283
TI  - Exposing women to workplace stress factors as a risk factor for developing
      arterial hypertension.
AB  - The purpose of this study is the evaluation of women's exposure to stress
      inducing factors at work, definition of a scale of the problem, as well as
      assessment of the impact of professional work on the value of arterial pressure.
      The research was conducted on four professional groups of women: working in
      agriculture, working as clerks, seamstresses, as well as those working as medical
      representative in the period from August- September 2008 in the Lublin region. A
      total number of 416 women was examined, ages ranging from 30-40, who had not been
      previously treated due to arterial hypertension. The women under examination had
      their arterial blood pressure measured twice on a working day at 08:00 and at
      14:00. The values of measurements were averaged. The research tool was also the
      standardised Questionnaire for Subjective Work Evaluation. The raw result was
      obtained on the basis of summing up all the points, which were afterwards
      transformed into 10 standard values. The general result was given in 10 standard
      values, whereas the results of stress factors were quoted as mean results of raw
      values and were referred to results defined as high for a given factor. The
      results obtained were statistically analysed on the basis of t-Student test. The
      significance level adopted was p<0.05. The results obtained in a particular
      professional group were compared as well as the impact of socio-demographic
      variables, such as level of education, marital status, place of residence, on the
      intensification of stress related to a particular factor of work evaluation, was
      also analysed. Stress experienced by women at a workplace affects not ony their
      professional life, but also family life and social intercourses. In the women's
      opinion, an unpleasant workplace is such a workplace where the feeling of mental
      workload is connected with the lack of rewards (motivation), uncertainty
      resulting from organisation of daily chores and lack of support from others. The
      high general level of stress was noted among the group of women working in
      agriculture, in pharmaceutical companies, as well as among those who perform
      physical work (seamstresses). The intensification of stress at a workplace had a
      considerable impact on the value of arterial pressure among the group of woman
      medical representatives, as well as among the group of woman office workers. No
      significant dependencies were concluded between socio-demographic variables and
      the general level of exposure to intensified stress in the examined professional
      groups. The above research confirms the need for further examination of the
      working environment of women and its impact on health. Obviously, attempts should
      be made in order to improve the conditions of work for women, bearing in mind the
      fact that the adoption of neutral attitude towards the sexes when assessing risk
      and undertaking preventive activities may result in the female gender being
      underestimated or even disregarded.

PMID- 21736284
TI  - Prevention of female reproductive system cancer among rural and urban Polish
      pregnant women.
AB  - Based on data obtained from the system MoZMaD - PL (Polish Mother and Child
      Health Monitoring System; an equivalent of the American system PRAMS (Pregnancy
      Risk Assessment Monitoring System). In the developed countries prevention
      programmes proved to be efficient in reducing morbidity and mortality due to
      breast and cervical cancer. In Poland, these diseases still constitute a very big
      problem, despite relatively easy and early diagnostics of pathological conditions
      preceding their development. The objective of the study was analysis of the usage
      of prophylactic examinations and the assessment of knowledge concerning risk
      factors of the development of reproductive cancers among pregnant women from
      rural and urban environments in Poland. The study was based on questionnaire
      forms within the Pregnancy Risk Assessment Monitoring System (MoZMaD - PL)
      implemented in Poland. The precise date of the study for the whole of Poland is
      announced annually by the Chief Sanitary Inspector. The questionnaire forms were
      correctly completed in 2010 by 2,877 women. The replies to the questions were
      introduced by surveyors into the MoZMaD - PL system central database managed by
      the Institute of Agricultural Medicine in Lublin. The results obtained were
      subjected to statistical analysis. The studies of pregnant women in Poland showed
      that the situation with respect to the performance of prevention examinations for
      cervical cancer was significantly worse among rural than urban women. Pregnant
      women from both rural and urban areas very rarely had breast USG performed.
      Awareness concerning cervical cancer risk factors was lower among rural than
      urban women. Also, knowledge concerning the examinations which should be
      performed for the prevention of breast cancer was poorer among rural, compared to
      urban women. The recognition of the attitudes of women at reproductive age
      towards prevention examinations is necessary in order to effectively plan health
      education and social health promotion campaigns aimed at limiting morbidity and
      mortality due to cancerous diseases.

PMID- 21736285
TI  - Endonuclease active site plasticity allows DNA cleavage with diverse alkaline
      Earth and transition metal ions.
AB  - A majority of enzymes show a high degree of specificity toward a particular metal
      ion in their catalytic reaction. However, Type II restriction endonuclease
      (REase) R.KpnI, which is the first member of the HNH superfamily of REases,
      exhibits extraordinary diversity in metal ion dependent DNA cleavage. Several
      alkaline earth and transition group metal ions induce high fidelity and
      promiscuous cleavage or inhibition depending upon their concentration. The metal
      ions having different ionic radii and co-ordination geometries readily replace
      each other from the enzyme's active site, revealing its plasticity. Ability of
      R.KpnI to cleave DNA with both alkaline earth and transition group metal ions
      having varied ionic radii could imply utilization of different catalytic site(s).
      However, mutation of the invariant His residue of the HNH motif caused abolition
      of the enzyme activity with all of the cofactors, indicating that the enzyme
      follows a single metal ion catalytic mechanism for DNA cleavage. Indispensability
      of His in nucleophile activation together with broad cofactor tolerance of the
      enzyme indicates electrostatic stabilization function of metal ions during
      catalysis. Nevertheless, a second metal ion is recruited at higher concentrations
      to either induce promiscuity or inhibit the DNA cleavage. Regulation of the
      endonuclease activity and fidelity by a second metal ion binding is a unique
      feature of R.KpnI among REases and HNH nucleases. The active site plasticity of
      R.KpnI opens up avenues for redesigning cofactor specificities and generation of
      mutants specific to a particular metal ion.

PMID- 21736287
TI  - Synthesis of L-epi-capreomycidine derivatives via C-H amination.
AB  - The L-epi-capreomycidine (Cpm) derivatives were efficiently and stereoselectively
      synthesized via nitrene C-H insertion starting from a readily available D-Tyr.
      Design of a substrate that takes into account hydrogen bonding is a critical
      feature in order to achieve high selectivity. Our synthetic strategy could be a
      new access to epi-Cpm and its derivatives, which are found in several
      biologically active natural products.

PMID- 21736288
TI  - A tertiary amine as a hydride donor: trichlorosilyl triflate-mediated conjugate
      reduction of unsaturated ketones.
AB  - Bulky tertiary amines, especially dicyclohexylisobutylamine, smoothly reduced
      alpha,beta-unsaturated ketones in the presence of trichlorosilyl triflate to give
      the corresponding saturated ketones in excellent yields. Isotope-labeling studies
      revealed that an alpha-hydrogen of the amine was transferred to the enones during
      reduction.

PMID- 21736289
TI  - One-step electrochemical synthesis of PtNi nanoparticle-graphene nanocomposites
      for nonenzymatic amperometric glucose detection.
AB  - We report a facile one-step ultrasonication-assisted electrochemical method to
      synthesize nanocomposites of graphene and PtNi alloy nanoparticles (NPs) and
      their uses for highly selective nonenzymatic glucose detection. We have
      demonstrated that the obtained nanocomposites exhibit a collection of unique
      features including well-dispersed NPs with alloy features, high NP loading, and
      effective reduction of graphene oxide (GO). And the resulting nanoelectrocatalyst
      shows significantly improved electrochemical performance in nonenzymatic
      amperometric glucose detection, compared to a number of control electrode
      materials including the PtNi NP-chemically reduced GO nanocomposites fabricated
      in two steps (chemical reduction of GO followed by the electrodeposition of metal
      NPs). Under the physiological condition, the response current of the sensor is
      linear to glucose concentration up to 35 mM with a sensitivity of 20.42 MUA cm(
      2) mM(-1) at a substantially negative potential (i.e., -0.35 V). Operation under
      this potential eliminates the impact from the oxidation of common interfering
      species. This sensor with excellent sensitivity and selectivity also allows for
      reproducible detection of glucose in human urine samples.

PMID- 21736290
TI  - QTAIM charge-charge flux-dipole flux interpretation of electronegativity and
      potential models of the fluorochloromethane mean dipole moment derivatives.
AB  - Infrared fundamental vibrational intensities and quantum theory atoms in
      molecules (QTAIM) charge-charge flux-dipole flux (CCFDF) contributions to the
      polar tensors of the fluorochloromethanes have been calculated at the QCISD/cc
      pVTZ level. A root-mean-square error of 20.0 km mol(-1) has been found compared
      to an experimental error estimate of 14.4 and 21.1 km mol(-1) for MP2/6
      311++G(3d,3p) results. The errors in the QCISD polar tensor elements and mean
      dipole moment derivatives are 0.059 e when compared with the experimental values.
      Both theoretical levels provide results showing that the dynamical charge and
      dipole fluxes provide significant contributions to the mean dipole moment
      derivatives and tend to be of opposite signs canceling one another. Although the
      experimental mean dipole moment derivative values suggest that all the
      fluorochloromethane molecules have electronic structures consistent with a simple
      electronegativity model with transferable atomic charges for their terminal
      atoms, the QTAIM/CCFDF models confirm this only for the fluoromethanes. Whereas
      the fluorine atom does not suffer a saturation effect in its capacity to drain
      electronic charge from carbon atoms that are attached to other fluorine and
      chlorine atoms, the zero flux electronic charge of the chlorine atom depends on
      the number and kind of the other substituent atoms. Both the QTAIM carbon charges
      (r = 0.990) and mean dipole moment derivatives (r = 0.996) are found to obey
      Siegbahn's potential model for carbon 1s electron ionization energies at the
      QCISD/cc-pVTZ level. The latter is a consequence of the carbon mean derivatives
      obeying the electronegativity model and not necessarily to their similarities
      with atomic charges. Atomic dipole contributions to the neighboring atom
      electrostatic potentials of the fluorochloromethanes are found to be of
      comparable size to the atomic charge contributions and increase the accuracy of
      Siegbahn's model for the QTAIM charge model results. Substitution effects of the
      hydrogen, fluorine, and chlorine atoms on the charge and dipole flux QTAIM
      contributions are found to be additive for the mean dipole derivatives of the
      fluorochloromethanes.

PMID- 21736291
TI  - Melting of the precipitated ice IV in LiCl aqueous solution and polyamorphism of
      water.
AB  - Melting of the precipitated ice IV in supercooled LiCl-H(2)O solution was studied
      in the range of 0-0.6 MPa and 160-270 K. Emulsified solution was used to detect
      this metastable transition. Ice IV was precipitated from the aqueous solution of
      2.0 mol % LiCl (or 4.8 mol % LiCl) in each emulsion particle at low-temperature
      and high-pressure conditions, and the emulsion was decompressed at different
      temperatures. The melting of ice IV was detected from the temperature change of
      the emulsified sample during the decompression. There was an apparently sudden
      change in the slope of the ice IV melting curve (liquidus) in the pressure
      temperature diagram. At the high-pressure and high-temperature side of the
      change, the solute-induced freezing point depression was observed. At the low
      pressure and low-temperature side, ice IV transformed into ice Ih on the
      decompression, and the transition was almost unrelated to the concentration of
      LiCl. These experimental results were roughly explained by the presumed existence
      of two kinds of liquid water (low-density liquid water and high-density liquid
      water), or polyamorphism in water, and by the simple assumption that LiCl
      dissolved maily in high-density liquid water.

PMID- 21736292
TI  - Simple fabrication of a Pd-P film on a polymer membrane and its catalytic
      applications.
AB  - Composites were prepared by a surface activation by aerosol deposition of Pd
      nanoparticles (Pd nano seeds) on a poly(tetrafluoroethylene) membrane and
      subsequent Pd-P film formation by electroless deposition. Activation of the
      membrane processed by an ambient Pd spark discharge and subsequent fixation of
      the spark produced Pd nano seeds. Characterizations for electroless Pd-P films
      indicated that P entered into the crystal lattice of Pd and formed an alloy. The
      fabricated composites were applied to catalytic applications of formic acid
      oxidation (FAO) and toluene conversion (TC). The composite catalysts from the
      simple activation had more stable performances of FAO and TC than those from the
      conventional Sn-Pd activation, and their better performances might have
      originated from better purity due to the simple activation that only introduced
      pure Pd nano seeds.

PMID- 21736293
TI  - Reexamination of the Rehm-Weller data set reveals electron transfer quenching
      that follows a Sandros-Boltzmann dependence on free energy.
AB  - In a landmark publication over 40 years ago, Rehm and Weller (RW) showed that the
      electron transfer quenching constants for excited-state molecules in acetonitrile
      could be correlated with the excited-state energies and the redox potentials of
      the electron donors and acceptors. The correlation was interpreted in terms of
      electron transfer between the molecules in the encounter pair (A*/D ? A(*-)/D(*+)
      for acceptor A and donor D) and expressed by a semiempirical formula relating the
      quenching constant, k(q), to the free energy of reaction, DeltaG. We have
      reinvestigated the mechanism for many Rehm and Weller reactions in the endergonic
      or weakly exergonic regions. We find they are not simple electron transfer
      processes. Rather, they involve exciplexes as the dominant, kinetically and
      spectroscopically observable intermediate. Thus, the Rehm-Weller formula rests on
      an incorrect mechanism. We have remeasured k(q) for many of these reactions and
      also reevaluated the DeltaG values using accurately determined redox potentials
      and revised excitation energies. We found significant discrepancies in both
      DeltaG and k(q), including A*/D pairs at high endergonicity that did not exhibit
      any quenching. The revised data were found to obey the Sandros-Boltzmann (SB)
      equation k(q) = k(lim)/[1 + exp[(DeltaG + s)/RT]]. This behavior is attributed to
      rapid interconversion among the encounter pairs and the exciplex (A*/D ? exciplex
      ? A(*-)/D(*+)). The quantity k(lim) represents approximately the diffusion
      limited rate constant, and s the free energy difference between the radical ion
      encounter pair and the free radical ions (A(*-)/D(*+) vs A(*-) + D(*+)). The
      shift relative to DeltaG for the overall reaction is positive, s = 0.06 eV,
      rather than the negative value of -0.06 eV assumed by RW. The positive value of s
      involves the poorer solvation of A(*-)/D(*+) relative to the free A(*-) + D(*+),
      which opposes the Coulombic stabilization of A(*-)/D(*+). The SB equation does
      not involve the microscopic rate constants for interconversion among the
      encounter pairs and the exciplex. Data that fit this equation contain no
      information about such rate constants except that they are faster than
      dissociation of the encounter pairs to (re-)form the corresponding free species
      (A* + D or A(*-) + D(*+)). All of the present conclusions agree with our recent
      results for quenching of excited cyanoaromatic acceptors by aromatic donors, with
      the two data sets showing indistinguishable dependencies of k(q) on DeltaG.

PMID- 21736294
TI  - Sensing of digestive proteins in saliva with a molecularly imprinted
      poly(ethylene-co-vinyl alcohol) thin film coated quartz crystal microbalance
      sensor.
AB  - The quartz crystal microbalance (QCM) has a sensitivity comparable to that of the
      surface plasmon resonance (SPR) transducer. Molecularly imprinted polymers (MIPs)
      have a much lower cost than natural antibodies, they are easier to fabricate and
      more stable, and they exhibit satisfactory recognition ability when integrated
      onto sensing transducers. Hence, MIP-based QCM sensors have been used to
      recognize small molecules and, recently, microorganisms, but only a few have been
      adopted in protein sensing. In this work, a mixed salivary protein and
      poly(ethylene-co-vinyl alcohol), EVAL, solution is coated onto a QCM chip and a
      molecularly imprinted EVAL thin film formed by thermally induced phase separation
      (TIPS). The optimal ethylene mole ratios of the commercially available EVALs for
      the imprinting of amylase, lipase and lysozyme were found to be 32, 38, and 44
      mol %, respectively. Finally, the salivary protein-imprinted EVAL-based QCM
      sensors were used to detect amylase, lipase and lysozyme in real samples (saliva)
      and their effectiveness was compared with that of a commercial ARCHITECT ci 8200
      chemical analysis system. The limits of detection (LOD) for those salivary
      proteins were as low as ~pM.

PMID- 21736295
TI  - Low temperature neutron diffraction studies in [Mn3(suc)2(ina)2]n: an
      homometallic molecular 3D ferrimagnet.
AB  - Neutron diffraction techniques have been used to determine the low temperature
      crystal structure and to shed light on the magnetic behavior of the
      [Mn(3)(suc)(2)(ina)(2)](n) (suc = succinate and ina = isonicotinate) complex. The
      ferromagnetic signal observed below T(c) ~ 5 K in this compound is due to a
      noncompensation of homometallic spins in the 3D framework. The Mn(II) magnetic
      moments obtained from neutron diffraction refinements are slightly lower than
      those observed for isolated Mn(II) ions; this can be due to covalent spin
      delocalization or geometrical magnetic fluctuations. A small discrepancy between
      the value of the magnetic moments of each Mn(II) site is also observed [Mn(1)
      4.1(2) MU(B) and the Mn(2) 3.9(1) MU(B)]. These differences between the
      theoretical and observed manganese magnetic moments are not unexpected in this
      large spin metal complex, and qualitatively reasonable given the synergistic
      interaction between the metal ions through oxo-bridge. The competition among
      different interactions, principally those covalent through organic ligands and
      dipolar interaction, drive to a final 3D ferrimagnetic order.

PMID- 21736296
TI  - Extrusion-induced changes to the chemical profile and viscosity generating
      properties of citrus fiber.
AB  - Each of 8 variants in extrusion conditions was applied to a commercially
      available citrus fiber. Extrusion under conditions where the specific mechanical
      energy (SME) exceeded 400 kJ.kg(-1) was able to solubilize up to 30% of the
      fibers. Where the SME was ~200 kJ.kg(-1) the degree of fiber solubilization was
      between 8 and 12%. All extruded fibers showed a loss of water-retaining capacity
      compared to the reference fiber, and this was attributed to the disruption of the
      integrated cell wall structure during the extrusion process. Nevertheless, within
      the 8 extruded variants there was a wide range of viscosity generating capacity
      which depended on the level of SME to which the fibers were subjected. The SME
      also had a pronounced effect on the nature of the solubilized fibers in terms of
      both their monosaccharide composition and their molecular weight profile. Both
      pectic and hemicellulosic polysaccharides were solubilized. It is concluded that
      extrusion has promise as a physical process for manipulating both the
      technological functionality and the health promoting properties of dietary
      fibers.

PMID- 21736297
TI  - Matrix infrared spectra and density functional calculations of the H2CCN and
      H2CNC radicals produced from CH3CN.
AB  - The H(2)CCN and H(2)CNC radicals are observed in matrix IR spectra from
      acetonitrile exposed to radiation from laser ablation of transition metals,
      whereas cyc-H(2)CCN, another plausible isomer, is not. Density functional
      frequency calculations and D and (13)C isotopic substitutions substantiate the
      vibrational assignments. The cyano methyl radical converts to the 95 kJ/mol
      higher energy isocyano counterpart on uv photolysis. Computations show that the
      cyclic isomer is a shallow energy minimum between two transition states.
      Intrinsic reaction coordinate calculations indicate that conversion between the
      two products is feasible via the cyclic configuration.

PMID- 21736298
TI  - Nanostructure on taro leaves resists fouling by colloids and bacteria under
      submerged conditions.
AB  - The antifouling and self-cleaning properties of plants such as Nelumbo nucifera
      (lotus) and Colocasia esculenta (taro) have been attributed to the
      superhydrophobicity resulting from the hierarchical surface structure of the leaf
      and the air trapped between the nanosized epicuticular wax crystals. The reported
      study showed that the nanostructures on the taro leaf surfaces were also highly
      resistant to particle and bacterial adhesion under completely wetted conditions.
      Adhesion force measurements using atomic force microscopy revealed that the
      adhesion force on top of the papilla as well as the area around it was markedly
      lower than that on the edge of an epidermal cell. The decreased adhesion force
      and the resistance to particle and bacterial adhesion were attributed to the
      dense nanostructures found on the epidermal papilla and the area surrounding it.
      These results suggest that engineered surfaces with properly designed nanoscale
      topographic structures could potentially reduce or prevent particle/bacterial
      fouling under submerged conditions.

PMID- 21736299
TI  - The Werner and Bloom syndrome proteins help resolve replication blockage by
      converting (regressed) holliday junctions to functional replication forks.
AB  - Cells cope with blockage of replication fork progression in a manner that allows
      DNA synthesis to be completed and genomic instability minimized. Models for
      resolution of blocked replication involve fork regression to form Holliday
      junction structures. The human RecQ helicases WRN and BLM (deficient in Werner
      and Bloom syndromes, respectively) are critical for maintaining genomic stability
      and thought to function in accurate resolution of replication blockage.
      Consistent with this notion, WRN and BLM localize to sites of blocked replication
      after certain DNA-damaging treatments and exhibit enhanced activity on
      replication and recombination intermediates. Here we examine the actions of WRN
      and BLM on a special Holliday junction substrate reflective of a regressed
      replication fork. Our results demonstrate that, in reactions requiring ATP
      hydrolysis, both WRN and BLM convert this Holliday junction substrate primarily
      to a four-stranded replication fork structure, suggesting they target the
      Holliday junction to initiate branch migration. In agreement, the Holliday
      junction binding protein RuvA inhibits the WRN- and BLM-mediated conversion
      reactions. Importantly, this conversion product is suitable for replication with
      its leading daughter strand readily extended by DNA polymerases. Furthermore,
      binding to and conversion of this Holliday junction are optimal at low MgCl(2)
      concentrations, suggesting that WRN and BLM preferentially act on the square
      planar (open) conformation of Holliday junctions. Our findings suggest that,
      subsequent to fork regression events, WRN and/or BLM could re-establish
      functional replication forks to help overcome fork blockage. Such a function is
      highly consistent with phenotypes associated with WRN- and BLM-deficient cells.

PMID- 21736300
TI  - Strong stabilization of amorphous calcium carbonate emulsion by ovalbumin:
      gaining insight into the mechanism of 'polymer-induced liquid precursor'
      processes.
AB  - The impact of the ovo proteins ovalbumin and lysozyme--present in the first stage
      of egg shell formation--on the homogeneous formation of the liquid amorphous
      calcium carbonate (LACC) precursor, was studied by a combination of complementing
      methods: in situ WAXS, SANS, XANES, TEM, and immunogold labeling. Lysozyme (pI =
      9.3) destabilizes the LACC emulsion whereas the glycoprotein ovalbumin (pI = 4.7)
      extends the lifespan of the emulsified state remarkably. In the light of the
      presented data: (a) Ovalbumin is shown to behave commensurable to the 'polymer
      induced liquid precursor' (PILP) process proposed by Gower et al. Ovalbumin can
      be assumed to take a key role during eggshell formation where it serves as an
      effective stabilization agent for transient precursors and prevents undirected
      mineralization of the eggshell. (b) It is further shown that the emulsified LACC
      carries a negative surface charge and is electrostatically stabilized. (c) We
      propose that the liquid amorphous calcium carbonate is affected by polymers by
      depletion stabilization and de-emulsification rather than 'induced' by acidic
      proteins and polymers during a so-called polymer-induced liquid-precursor
      process. The original PILP coating effect, first reported by Gower et al.,
      appears to be a result of a de-emulsification process of a stabilized LACC phase.
      The behavior of the liquid amorphous carbonate phase and the polymer-induced
      liquid-precursor phase itself can be well described by colloid chemical terms:
      electrostatic and depletion stabilization and de-emulsification by depletion
      destabilization.

PMID- 21736301
TI  - Electronic communication between two amine redox centers bridged by a
      bis(terpyridine)ruthenium(II) complex.
AB  - Two bis(terpyridine)ruthenium(II) complexes 2 and 3 appended with one or two di-p
      anisylamino groups, respectively, were synthesized and fully characterized. Their
      electronic properties were studied by electrochemical and spectroscopic analyses.
      Electronic communication between individual amine sites of 3 was estimated by
      intervalence charge-transfer band analyses.

PMID- 21736302
TI  - Expanding family of pi-conjugated trinuclear dithiolenes: the cases of group 8
      (Ru(II)) and 10 (Ni(II) and Pt(II)) metals.
AB  - New pi-conjugated trinuclear dithiolenes with group 8 (6, Ru(II)) and 10 (7 and
      8, Ni(II) and Pt(II)) metals were synthesized. Compounds 6 and 7 exhibited
      intense electronic communication through the phenylene bridge among the three
      dithiolene moieties during oxidation of the metalladithiolene rings, which has
      not been confirmed in the analogous family of group 9 metals, 1-5. Compound 8
      exhibited an intense absorption band across the visible and near-IR regions,
      which was assigned as a charge transfer to the diimine and was red-shifted and
      broadened compared to the corresponding band of the mononuclear complex.

PMID- 21736303
TI  - Preparation of alpha-alkyl-beta-amino acids via beta-alanine Ni(II) complex.
AB  - A new beta-amino acrylic acid Ni(II) complex has been developed and used for the
      synthesis of alpha-alkyl-beta-amino acids via alkylation with alkyl halides under
      operationally convenient conditions. The pivotal alpha-alkylated intermediate can
      be converted into the corresponding alpha-alkyl-beta-amino acids via two steps
      with a wide range of substituents.

PMID- 21736304
TI  - Deoxyfluorination of phenols.
AB  - An operationally simple ipso fluorination of phenols with a new deoxyfluorination
      reagent is presented.

PMID- 21736305
TI  - Effects on membrane lateral pressure suggest permeation mechanisms for bacterial
      quorum signaling molecules.
AB  - Quorum sensing is an intricate example of "social" behavior in microbial
      communities mediated by small secreted molecules (autoinducers). The mechanisms
      of membrane permeation remain elusive for many of them. Here we present the
      assessment of membrane permeability for three natural autoinducers and four
      synthetic analogues based on their polarity, surface activity, affinity for lipid
      monolayers, and ability to induce lateral pressure changes in the inner E. coli
      membrane sensed by the bacterial tension-activated channel MscS. AI-1 (N-(3
      oxodecanoyl)-l-homoserine lactone) is surface-active, and it robustly inserts
      into lipid monolayers, indicating strong propensity toward membranes. When
      presented to membrane patches from the cytoplasmic side, AI-1 transiently shifts
      MscS's activation curve toward higher tensions due to intercalation into the
      cytoplasmic leaflet followed by redistribution to the opposite side. Indole
      showed no detectable surface activity at the air-water interface but produced a
      moderate increase of lateral pressure in monolayers and was potent at shifting
      activation curves of MscS, demonstrating transients on sequential additions. AI-2
      (4,5-dihydroxy-2,3-pentanedione, DPD) showed little activity at the interfaces,
      correspondingly with no effect on MscS activation. After chemical modification
      with isobutyl, hexyl, or heptyl chains, AI-2 displayed strong surface activity.
      Hexyl and especially heptyl AI-2 induced robust transient shifts of MscS
      activation curves. The data strongly suggest that both AI-1 and indole are
      directly permeable through the membrane. AI-2, more hydrophilic, shows low
      affinity toward lipids and thus requires a transport system, whereas alkyl
      analogues of AI-2 should permeate the membrane directly.

PMID- 21736306
TI  - Synthesis, characterization and antibacterial activity against Gram positive and
      Gram negative bacteria of biomimetically coated silver nanoparticles.
AB  - In the present work, we describe a simple procedure to produce biomimetically
      coated silver nanoparticles (Ag NPs), based on the postfunctionalization and
      purification of colloidal silver stabilized by citrate. Two biological capping
      agents have been used (cysteine Cys and glutathione GSH). The composition of the
      capped colloids has been ascertained by different techniques and antibacterial
      tests on GSH-capped Ag NPs have been conducted under physiological conditions,
      obtaining values of Minimum Inhibitory Concentration (MIC) of 180 and 15 MUg/mL
      for Staphylococcus aureus and Escherichia coli, respectively. The antibacterial
      activity of these GSH capped NPs can be ascribed to the direct action of metallic
      silver NPs, rather than to the bulk release of Ag(+).

PMID- 21736307
TI  - Mechanistic insight into olefin epoxidation catalyzed by rhenium(V) oxo complexes
      that contain pyridazine-based ligands.
AB  - Three novel tridentate pyridazine phenolate ligands were prepared in high yields
      by Schiff-base condensation of salicylic aldehyde with various pyridazine
      hydrazines (substituent R in the 6 position: R = Cl (HL(Cl)), (t)Bu (HL((t)Bu)),
      or tol (HL(tol))). They react with [ReOCl(3)(OPPh(3))(SMe(2))] to form rare
      mononuclear trans-dichloro oxo complexes of general formula [ReOCl(2)(L(R))] with
      R = tol (1), (t)Bu (2), or Cl (3) as confirmed by single-crystal X-ray
      diffraction analyses of 1 and 2. They were found to be catalysts for oxidation of
      cyclooctene to the corresponding epoxide by tert-butyl hydroperoxide (TBHP).
      Extensive UV-vis and NMR spectroscopic investigations followed by evaluation
      using the powerful Mauser method revealed mechanistic details. This showed the
      catalyst precursor [ReOCl(2)(L)] (2) to be transformed into the rhenium(VII)
      compound [ReO(3)L] (4) in a two-step reaction via intermediate INT which is
      tentatively assigned to [ReO(2)L]. Confirmation gave the isolation of 4 by
      reaction of 2 with excess of TBHP. Monitoring the catalytic oxidation reaction by
      UV-vis spectroscopy clearly excludes the two rhenium(V) compounds 2 and INT from
      being the catalytically active species as their formation is several orders of
      magnitude faster than the observed catalytic epoxidation reaction.

PMID- 21736309
TI  - Enantiomer recognition of amides by dirhodium(II) tetrakis[methyl 2
      oxopyrrolidine-5(S)-carboxylate].
AB  - Association constants of the chiral dirhodium(II) carboxamidate Rh(2)(5S-MEPY)(4)
      with Lewis bases including acetonitrile and amides have been determined by UV-vis
      titration experiments. With chiral lactams and acyclic acetamides in their R- and
      S-configurations equilibrium constants with chiral dirhodium carboxamidates are
      measures of chiral differentiation, and equilibrium constant ratios as high as
      three have been determined. From equilibrium associations with acetamide, N
      methylacetamide, and N,N-dimethylacetamide, as well as equilibrium constants for
      lactams and acyclic amides, higher values occur when both the amide carbonyl
      oxygen and N-H are bound to Rh(2)(5S-MEPY)(4). This cooperative bonding mode is
      confirmed by NMR measurements that show a distinctive shift of a N-H absorption,
      as well as perturbation of the ligands on dirhodium compound, and they suggest N
      H association with a ligated oxygen of Rh(2)(5S-MEPY)(4). Measurements were made
      on the dirhodium(II) compound from which protective axial ligands have been
      removed to enhance their reliability.

PMID- 21736310
TI  - Semirigid aromatic sulfone-carboxylate molecule for dynamic coordination
      networks: multiple substitutions of the ancillary ligands.
AB  - We report dynamic, multiple single-crystal to single-crystal transformations of a
      coordination network system based on a semirigid molecule, TCPSB = 1,3,5-tri(4'
      carboxyphenylsulphonyl)benzene, which nicely balances shape persistence and
      flexibility to bring about the framework dynamics in the solid state. The
      networks here generally consist of (1) the persistent core component (denoted as
      CoTCPSB) of linear Co(II) aqua clusters (Co-O-Co-O-Co) integrated into 2D grids
      by 4,4'-bipyridine and TCPSB and (2) ancillary ligands (AL) on the two terminal
      Co(II) ions-these include DMF (N,N'-dimethylformamide), DMA (N,N'
      dimethylacetamide), CH(3)CN, and water. Most notably, the ancillary ligand sites
      are highly variable and undergo multiple substitution sequences while maintaining
      the solid reactants/products as single-crystals amenable to X-ray structure
      determinations. For example, when immersed in CH(3)CN, the AL of an as-made
      single crystal of CoTCPSB-DMF (i.e., DMF being the AL) is replaced to form
      CoTCPSB-CH(3)CN, which, in air, readily loses CH(3)CN to form CoTCPSB-H(2)O; the
      CoTCPSB-H(2)O single crystals, when placed in DMF, give back CoTCPSB-DMF in
      single-crystal form. Other selective, dynamic exchanges include the following:
      CoTCPSB-DMF reacts with CH(3)CN (to form CoTCPSB-CH(3)CN) but NOT with water,
      methanol, ethanol, DMA, or pyridine; CoTCPSB-H(2)O specifically pick outs DMF
      from a mixture of DMF, DMA, and DEF; an amorphous, dehydrated solid from CoTCPSB
      H(2)O regains crystalline order simply by immersion in DMF (to form CoTCPSB-DMF).
      Further exploration with functional, semirigid ligands like TCPSB shall continue
      to uncover a wider array of advanced dynamic behaviors in solid state materials.

PMID- 21736311
TI  - Direct synthesis of fluorescent 1,3a,6a-triazapentalene derivatives via click
      cyclization-aromatization cascade reaction.
AB  - An efficient and versatile method was established for the preparation of 1,3a,6a
      triazapentalenes. The 1,3a,6a-triazapentalene skeleton without an additional
      fused ring system was discovered to be a compact and highly fluorescent
      chromophore, which exhibited various interesting fluorescent properties such as a
      noteworthy correlation of luminescent wavelength with the Hammett sigma(p) value
      and a strongly positive solvatofluorochromism.

PMID- 21736312
TI  - Foamability and foam stability of molecular reconstituted model sparkling wines.
AB  - The present work aims at identifying the contribution of the different wine
      components to the foaming properties of wines. Twelve fractions were isolated
      from wine, and foam aptitude of each fraction was measured individually at the
      concentration at which it was recovered, using wine model solutions. For these
      concentrations, the maximum foam height (HM) was 8.4-11.7 cm, foam height on
      stability was 6.9-7.5 cm, and foam stability (TS) was 3.0-6.5 s. Moreover, foam
      measurements were also performed using 2-, 5-, and 10-fold concentrations of
      these compounds in wine. The HM increased linearly with the concentration of
      mannoproteins having low content of protein (MP1), and TS increased
      exponentially. The fractions that individually showed higher foaming properties
      were mixed in binary and ternary combinations, demonstrating that MP1 when mixed
      with low molecular weight hydrophobic compounds strengthens the air/water
      interface of these solutions, a characteristic that is on the basis of sparkling
      wines' foamability and foam stability.

PMID- 21736313
TI  - A transient kinetic analysis of PRMT1 catalysis.
AB  - Post-translational modifications (PTMs) are important strategies used by
      eukaryotic organisms to modulate their phenotypes. One of the well-studied PTMs,
      arginine methylation, is catalyzed by protein arginine methyltransferases (PRMTs)
      with SAM as the methyl donor. The functions of PRMTs have been broadly studied in
      different biological processes and diseased states, but the molecular basis for
      arginine methylation is not well-defined. In this study, we report the transient
      state kinetic analysis of PRMT1 catalysis. The fast association and dissociation
      rates suggest that PRMT1 catalysis of histone H4 methylation follows a rapid
      equilibrium sequential kinetic mechanism. The data give direct evidence that the
      chemistry of methyl transfer is the major rate-limiting step and that binding of
      the cofactor SAM or SAH affects the association and dissociation of H4 with
      PRMT1. Importantly, from the stopped-flow fluorescence measurements, we have
      identified a critical kinetic step suggesting a precatalytic conformational
      transition induced by substrate binding. These results provide new insights into
      the mechanism of arginine methylation and the rational design of PRMT inhibitors.

PMID- 21736314
TI  - AFM imaging of adsorbed Nafion polymer on mica and graphite at molecular level.
AB  - Perfluorosulfonic acid ionomer (PFSA, specifically Nafion at EW = 975 g/mol) was
      visualized at the single molecule level using atomic force microscopy (AFM) in
      liquid. The diluted commercial Nafion dispersion shows an apparent M(w) = 1430
      kg/mol and M(w)/M(n) = 3.81, which is assigned to chain aggregation. PFSA
      aggregates, imaged on mica and HOPG during adsorption from EtOH-H(2)O solvent at
      pH(e) 3.0 (below isoelectric point), showed a stable, segmented rod-like
      conformation. This structure is consistent with earlier NMR, SAXS/SANS, and TEM
      results that support a stiff helical Nafion conformation with long persistence
      length, a sharp solvent-polymer interface, and an extension of the sulfonated
      side chain into solution. Adsorption of Nafion structures on HOPG was observed at
      even higher pH(e) from EtOH due to screening of the repulsive electrostatic
      interaction in lower dielectric constant solvent, while the chain adopted an
      expanded coil conformation. These measurements provided direct evidence of the
      chain aggregation in EtOH-H(2)O solution and revealed their equilibrium
      conformations for adsorption on two model surfaces, highly ordered pyrolitic
      graphite (HOPG) and mica. The commercial Nafion dispersion was autoclaved at
      0.10% w/w in nPrOH/H(2)O = 4:1 v/v solvent at 230  degrees C for 6 h to give a
      single-chain dispersion with M(w) = 310 kg/mol and M(w)/M(n) = 1.60. The
      autoclaved chains adopt an electrostatically stabilized compact globule
      conformation as observed by AFM imaging of the single PFSA molecules after rapid
      deposition on mica and HOPG at a low surface coverage.

PMID- 21736315
TI  - Preserving charge and oxidation state of Au(III) ions in an agent-functionalized
      nanocrystal model system.
AB  - Supporting functional molecules on crystal facets is an established technique in
      nanotechnology. To preserve the original activity of ionic metallorganic agents
      on a supporting template, conservation of the charge and oxidation state of the
      active center is indispensable. We present a model system of a metallorganic
      agent that, indeed, fulfills this design criterion on a technologically relevant
      metal support with potential impact on Au(III)-porphyrin-functionalized
      nanoparticles for an improved anticancer-drug delivery. Employing scanning
      tunneling microscopy and -spectroscopy in combination with photoemission
      spectroscopy, we clarify at the single-molecule level the underlying mechanisms
      of this exceptional adsorption mode. It is based on the balance between a high
      energy oxidation state and an electrostatic screening-response of the surface
      (image charge). Modeling with first principles methods reveals submolecular
      details of the metal-ligand bonding interaction and completes the study by
      providing an illustrative electrostatic model relevant for ionic metalorganic
      agent molecules, in general.

PMID- 21736316
TI  - Biomimetic engineering of modular bispecific antibodies for biomolecule
      immobilization.
AB  - Modular bispecific antibodies (BsAb's) that interact directly with a gold surface
      were engineered for immobilization on biosensing devices. The BsAb's consist of
      the variable fragments of antigold and antilysozyme antibodies connected via one
      of three linkers derived from naturally occurring proteins. The BsAb's were bound
      tightly to both the gold surface and to lysozyme, thus functioning as interface
      molecules between lysozyme and the gold surface without a substantial loss of
      antigen-binding activity. The antigen-binding capacity (the ratio of the amount
      of immobilized lysozyme to the amount of immobilized BsAb) on the gold surface
      reached 82%. An analysis of the correlation between binding capacity and linker
      characteristics indicated that the presence of a long, rigid linker sequence
      derived from a cellulase resulted in a higher antigen-binding capacity than did
      the presence of a long but relatively flexible glycine-rich linker. This result
      suggests a strategy for designing linkers suitable for BsAb-based biomolecular
      immobilization.

PMID- 21736317
TI  - N, P, and As ylides and aza- and arsa-Wittig reactions from topological analyses
      of electron density.
AB  - The nature of bonding between N, P, and As constituent atoms in ylide systems
      with the R(3)XYR' formula (X = N, P, As; Y = N, P, As; R = F, H; R' = H, CH(3))
      has been characterized by ab initio (MP2/6-311++G**) and density functional
      theory (B3LYP/6-311++G**) calculations. Its electronic structure has been
      analyzed through electron density with the quantum theory of atoms in molecules
      and the electron localization function (ELF). The characteristics of the central
      bond are inspected with the calculated rotational barriers. The results show that
      N has a behavior different from that of the remaining pnicogen atoms (P, As),
      where the bond is much stronger. Fluorine substituents strengthen the X-Y bond,
      reduce the bond distance, and increase the electron density in the central bond
      so that the substituent pulls charge from the bond in the pnicogen X atom. For
      the N-pnicogen ylides, the results showed different bonding characters between F
      and X atoms; depending on the position of the F atom, the difference of the bond
      character is sensed by the basin synaptic order, as it is deduced from the
      analysis of the ELF basins. The energy profiles of the rotational barriers have
      been calculated at the MP2/6-311++G** level, indicating that the
      electronegativity of the substituents is a relevant factor that has consequences
      in the characteristics of the X-Y bond.

PMID- 21736318
TI  - Solution synthesis of nanoparticular binary transition metal antimonides.
AB  - The preparation of nanoengineered materials with controlled nanostructures, for
      example, with an anisotropic phase segregated structure or a regular periodicity
      rather than with a broad range of interparticle distances, has remained a
      synthetic challenge for intermetallics. Artificially structured materials,
      including multilayers, amorphous alloys, quasicrystals, metastable crystalline
      alloys, or granular metals, are mostly prepared using physical gas phase
      procedures. We report a novel, powerful solution-mediated approach for the
      formation of nanoparticular binary antimonides based on presynthesized antimony
      nanoparticles. The transition metal antimonides M-Sb (M = Co, Ni, Cu(2), Zn) were
      obtained with sizes ranging from 20 and 60 nm. Through careful control of the
      reaction conditions, single-phase nanoparticular antimonides were synthesized.
      The nanophases were investigated by powder X-ray diffraction and (high
      resolution) electron microscopy. The approach is based on activated metal
      nanoparticles as precursors for the synthesis of the intermetallic compounds. X
      ray powder diffraction studies of reaction intermediates allowed monitoring of
      the reaction kinetics. The small particle size of the reactants ensures short
      diffusion paths, low activation barriers, and low reaction temperatures, thereby
      eliminating solid-solid diffusion as the rate-limiting step in conventional bulk
      scale solid-state synthesis.

PMID- 21736319
TI  - Crowding promotes the switch from hairpin to pseudoknot conformation in human
      telomerase RNA.
AB  - Formation of a pseudoknot (PK) in the conserved RNA core domain in the
      ribonucleoprotein human telomerase is required for function. In vitro experiments
      show that the PK is in equilibrium with an extended hairpin (HP) structure. We
      use molecular simulations of a coarse-grained model, which reproduces most of the
      salient features of the experimental melting profiles of PK and HP, to show that
      crowding enhances the stability of PK relative to HP in the wild type and in a
      mutant associated with dyskeratosis congenita. In monodisperse suspensions, small
      crowding particles increase the stability of compact structures to a greater
      extent than larger crowders. If the sizes of crowders in a binary mixture are
      smaller than that of the unfolded RNA, the increase in melting temperature due to
      the two components is additive. In a ternary mixture of crowders that are larger
      than the unfolded RNA, which mimics the composition of ribosome, large enzyme
      complexes and proteins in Escherichia coli , the marginal increase in stability
      is entirely determined by the smallest component. We predict that crowding can
      partially restore telomerase activity in mutants with decreased PK stability.

PMID- 21736320
TI  - Modeling oil droplets in plateau borders.
AB  - It is widely known that oil droplets can decrease the stability of aqueous films
      and foams. While less widely recognized, it has also been observed that oil
      droplets can, under certain circumstances, increase the stability of foams,
      especially if they are caught in the Plateau borders. In this paper, how the oil
      droplet deforms and is, in turn, deformed by the Plateau border is modeled using
      Surface Evolver. The two dimensionless parameters that affect these shapes are
      the size of the oil droplet relative to the Plateau border and the ratio of the
      oil-water interfacial tension to the air-water interfacial tension. The
      calculated pressures in all the phases were used to obtain the pressure exerted
      on the oil-water-air pseudoemulsion film, which allows the factors that influence
      the stability of these droplets in the Plateau border to be investigated. The
      final section of the paper demonstrates that the presence of an oil droplet in a
      Plateau border can have a major influence on the drainage of the aqueous phase
      along the Plateau border. This retardation of the flow would result in the oil
      droplets in the Plateau borders increasing the stability of foams in which they
      are found.

PMID- 21736321
TI  - Hydrogen uptake by {H[Mg(HCOO)3]?NHMe2}infinity and determination of its H2
      adsorption sites through Monte Carlo simulations.
AB  - A detailed analysis of the solvothermal synthesis in DMF of the polymeric
      magnesium formate {H[Mg(HCOO)(3)]?NHMe(2)}(infinity) (1) from
      Mg(ClO(4))(2).6H(2)O revealed that the final crystalline product is formed after
      an acid-catalyzed DMF hydrolysis, producing formic acid and dimethylamine. The
      former bridges magnesium(II) centers, creating the 3D scaffold, while the latter
      is trapped inside the cubic cavities of the polymer, engaging in strong hydrogen
      bonding with the formate ions of the cage. After thermal activation and guest
      removal, the material was tested for hydrogen uptake at T = 77 K over the 0-80
      bar pressure range, and the existence of preferred H(2) adsorption sites was
      assessed through grand canonical Monte Carlo (GCMC) simulations. No specific low
      energy site was found, and the H(2) molecules positions within the framework
      cavities are mainly dependent on packing effects. Thus, at low H(2) loadings the
      most populated site is the center of the cubic cavities, even though, at higher
      pressures, two more "localized" positions have been found by the simulation
      because of the reduced freedom of movement. The maximum experimental H(2) uptake
      corresponds to 8.8 mg/g or 13.5 mg/cm(3).

PMID- 21736322
TI  - Development of nanoscale inhomogeneities during drying of sol-gel derived
      amorphous lead zirconate titanate precursor thin films.
AB  - The structural evolution of sol-gel derived lead zirconate titanate (PZT)
      precursor films during and after physical drying was investigated by transmission
      electron microscopy (TEM), electron energy loss spectroscopy (EELS), selected
      area electron diffraction (SAED), and time-resolved X-ray diffraction (XRD).
      Films were deposited from initial 0.3 mol/dm(3) precursor sols with varying
      hydrolysis ratios. Zr-rich grains of 1-10 nm size, embedded in a Pb-, Zr-, and Ti
      containing amorphous matrix were found in as-dried films. The Zr-rich regions
      were crystalline at hydrolysis ratios [H(2)O]/[PZT] < 27.6, and amorphous at
      ratios > 100. X-ray diffraction analysis of PZT and zirconia sols revealed that
      the crystalline nanoparticles in both sols are identical and are probably
      composed of nanosized zirconium oxoacetate-like clusters. This study demonstrates
      that time-resolved X-ray diffraction combined with electron energy loss
      spectroscopy mapping is a powerful tool to monitor the nanoscale structural
      evolution of sol-gel derived thin films.

PMID- 21736323
TI  - Accurate analytical expressions for stripping voltammetry in the Henry adsorption
      limit.
AB  - A strategy is developed to derive accurate analytical expressions for low
      coverage cathodic stripping voltammetry. The procedure relies on the observation
      that diffusion affects the location of simulated voltammetric waves but not their
      shape, provided that physisorption of the analyte is negligible. As a proof of
      the generality of the proposed approach and having in mind the stripping of
      thiols, analytical solutions are derived for the cathodic stripping of monomers,
      dimers, and a mixture of monomers and dimers, whose reliability is proved by
      their comparison with numerically simulated voltammograms. Application to the
      deposition and reductive desorption of mercaptoacetic acid at a mercury electrode
      demonstrates that these approximate solutions can be used to get insights into
      the interfacial organization of incipient films. For this particular system, a
      transition from monomeric to dimeric behavior is identified upon increasing the
      thiol surface concentration. Further generalization of the proposed methodology
      is achieved by deriving an approximate analytical solution for thin-layer anodic
      stripping voltammetry, which is satisfactorily compared to the existing summation
      series solution.

PMID- 21736324
TI  - Inverse electron demand Diels-Alder reactions of 1,2,3-triazines: pronounced
      substituent effects on reactivity and cycloaddition scope.
AB  - A systematic study of the inverse electron demand Diels-Alder reactions of 1,2,3
      triazines is disclosed, including an examination of the impact of a C5
      substituent. Such substituents were found to exhibit a remarkable impact on the
      cycloaddition reactivity of the 1,2,3-triazine without altering, and perhaps even
      enhancing, the intrinsic cycloaddition regioselectivity. The study revealed not
      only that the reactivity may be predictably modulated by a C5 substituent (R =
      CO(2)Me > Ph > H) but also that the impact is of a magnitude to convert 1,2,3
      triazine (1) and its modest cycloaddition scope into a heterocyclic azadiene
      system with a reaction scope that portends extensive synthetic utility, expanding
      the range of participating dienophiles. Significantly, the studies define a now
      powerful additional heterocyclic azadiene, complementary to the isomeric 1,2,4
      triazines and 1,3,5-triazines, capable of dependable participation in inverse
      electron demand Diels-Alder reactions, extending the number of complementary
      heterocyclic ring systems accessible with implementation of the methodology.

PMID- 21736325
TI  - Build-up algorithm for atomic correspondence between chemical structures.
AB  - Determining a one-to-one atom correspondence between two chemical compounds is
      important to measure molecular similarities and to find compounds with similar
      biological activities. This calculation can be formalized as the maximum common
      substructure (MCS) problem, which is well-studied and has been shown to be NP
      complete. Although many rigorous and heuristic algorithms have been developed,
      none of these algorithms is sufficiently fast and accurate. We developed a new
      program, called "kcombu" using a build-up algorithm, which is a type of the
      greedy heuristic algorithms. The program can search connected and disconnected
      MCSs as well as topologically constrained disconnected MCS (TD-MCS), which is
      introduced in this study. To evaluate the performance of our program, we prepared
      two correct standards: the exact correspondences generated by the maximum clique
      algorithms and the 3D correspondences obtained from superimposed 3D structure of
      the molecules in a complex 3D structure with the same protein. For the five sets
      of molecules taken from the protein structure database, the agreement value
      between the build-up and the exact correspondences for the connected MCS is
      sufficiently high, but the computation time of the build-up algorithm is much
      smaller than that of the exact algorithm. The comparison between the build-up and
      the 3D correspondences shows that the TD-MCS has the best agreement value among
      the other types of MCS. Additionally, we observed a strong correlation between
      the molecular similarity and the agreement with the correct and 3D
      correspondences; more similar molecule pairs are more correctly matched.
      Molecular pairs with more than 40% Tanimoto similarities can be correctly matched
      for more than half of the atoms with the 3D correspondences.

PMID- 21736326
TI  - Effect of fullerene intercalation on the conformation and packing of poly-(2
      methoxy-5-(3'-7'-dimethyloctyloxy)-1,4-phenylenevinylene).
AB  - Photoluminescence (PL) and resonance Raman spectroscopy are used to track changes
      in the conformations and packing of poly-(2-methoxy-5-(3'-7'-dimethyloctyloxy)
      1,4-phenylenevinylene) (MDMO-PPV) chains with the addition of [6,6]-phenyl-C(61)
      butyric acid methyl ester (PCBM) molecules. PL lineshapes of MDMO-PPV thin films
      as a function of annealing time were first measured to determine the
      spectroscopic signatures of chain conformations and packing in the absence of
      PCBM. Annealing results in enhanced interchain interactions leading to red-shifts
      of PL 0-0 transitions by up to ~300 cm(-1) and apparent increases of the line
      shape Huang-Rhys factors. Wavelength-dependent PL lifetimes of as-cast and films
      annealed for short times (~30 s) are nonexponential with an instrument-limited
      component of ~100 ps and a ~350 ps component. With longer annealing times, decays
      become single exponential with an average lifetime of ~1 ns indicating that all
      excitations efficiently funnel to strongly coupled interchain sites. Addition of
      PCBM disrupts MDMO-PPV interchain interactions causing PL 0-0 transitions to blue
      shift, increases in line width, and decreases in apparent Huang-Rhys factors.
      Resonance Raman spectra of MDMO-PPV/PCBM thin films with variable PCBM weight
      fractions (~50:1 up to 1:8 w/w) were then measured using short (488 nm) and long
      (568 nm) excitation wavelengths. The out-of-plane vinylene C-H wag mode of MDMO
      PPV (~964 cm(-1)) showed pronounced increases in intensity of up to ~30% and red
      shifts of up to 5 cm(-1) with increasing PCBM content. These changes result from
      a decrease of planarity between chain segments that suppresses interchain
      interactions. Furthermore, red-shifts of up to ~4 cm(-1) were observed for the
      C?C symmetric stretch of the MDMO-PPV vinylene group (~1625 cm(-1)) with 488 nm
      excitation. The sensitivity of the MDMO-PPV vinylene group vibrations with PCBM
      indicates preferential interactions between these two molecules and is consistent
      with intercalation of PCBM into the polymer structure. This assignment was
      confirmed by thermally annealing of MDMO-PPV/PCBM films to remove intercalated
      PCBM molecules, which partially restores interchain interactions as seen from
      smaller intensity increases (~15%) and red-shifts (~2 cm(-1)) of the ~964 cm(-1)
      mode. Overall, the spectroscopic results show that MDMO-PPV chains adopt
      distorted conformations (i.e., less intrachain order and shorter conjugation
      lengths) that have important implications for explaining the structural origins
      for large improvements in charge mobilities in MDMO-PPV/PCBM blends.

PMID- 21736327
TI  - Diffusion-photodynamics coupling in Fluorescence Correlation Spectroscopy studies
      of photoswitchable Green Fluorescent Proteins: an analytical and simulative
      study.
AB  - The photodynamics of the Green Fluorescent Protein (GFP) has been addressed in
      detail, particularly by means of Fluorescence Correlation Spectroscopy (FCS), a
      technique that provides direct information when the diffusion and the
      photodynamics time scales are well separated. Efficient photoswitchable GFPs, a
      crucial component for applications in nanoscopy imaging, have long residence
      times in the dark state, typically longer than the diffusion time of the protein
      through the observation volume. In these cases, the effect of the coupling
      between photodynamics and the diffusion process on the analysis of the FCS
      measurements cannot be disregarded, and the use of FCS methods becomes therefore
      critical. This work deals with the analytical and simulative study of such
      coupling and indicates that the corrections to be applied to the conventional
      decoupled FCS model scale as the square root of the ratio between the diffusion
      and the dark state relaxation times. We discuss the possibility to estimate the
      extent of the diffusion/photodynamics coupling from the analysis of the inverse
      of the fluorescence autocorrelation function g(t), defined as G(-1)(g(t)) =
      g(0)/g(t) - 1. The function G(-1)(g(t)) is analyzed in terms of a parabolic
      expansion in which the curvature term directly provides the desired measure of
      the coupling. We validate the analytical prediction and the graphical estimate of
      the coupling on simulations of FCS experiments that are based on a coupled Monte
      Carlo-Brownian Dynamics algorithm. The analysis of the curvature of G(-1)(g(t)),
      applied to experimental FCS data of the photoswitchable E222Q mutant of GFPMut2
      (Mut2Q), indicates that the trapping rate for this chromophore is 3 orders of
      magnitude underestimated when the diffusion/photodynamics coupling is not taken
      into account and sheds some additional light on the complex energy diagram for
      this protein.

PMID- 21736328
TI  - Unraveling the protein targets of vancomycin in living S. aureus and E. faecalis
      cells.
AB  - Vancomycin is a potent glycopeptide antibiotic that has evolved to specifically
      bind to the D-Ala-D-Ala dipeptide termini of nascent peptidoglycans. Although
      this mode of action is well established, several studies indicate that vancomycin
      and analogues exploit noncanonical target sites. In order to address all
      vancomycin targets in clinically relevant Staphylococcus aureus and Enterococcus
      faecalis strains we developed a series of small-molecule photoaffinity probes
      based on vancomycin. Proteomic profiling revealed the specific labeling of two
      previously unknown vancomycin targets that are likely to contribute to its
      antibiotic activity. The specific inhibition of the major staphylococcal
      autolysin Atl confirms previous observations that vancomycin alters S. aureus
      cell morphology by interaction with the autolytic machinery. Moreover, in E.
      faecalis the vancomycin photoprobe specifically binds to an ABC transporter
      protein, which likely impedes the uptake of essential nutrients such as sugars
      and peptides. The labeling of these two prominent membrane targets in living
      cells reveals a thus far unexplored mode of vancomycin binding and inhibition
      that could allow a rational design of variants with improved activity.

PMID- 21736329
TI  - Rapid, photoactivatable turn-on fluorescent probes based on an intramolecular
      photoclick reaction.
AB  - Photoactivatable fluorescent probes are invaluable tools for the study of
      biological processes with high resolution in space and time. Numerous strategies
      have been developed in generating photoactivatable fluorescent probes, most of
      which rely on the photo-"uncaging" and photoisomerization reactions. To broaden
      photoactivation modalities, here we report a new strategy in which the
      fluorophore is generated in situ through an intramolecular tetrazole-alkene
      cycloaddition reaction ("photoclick chemistry"). By conjugating a specific
      microtubule-binding taxoid core to the tetrazole/alkene prefluorophores, robust
      photoactivatable fluorescent probes were obtained with fast photoactivation (~1
      min) and high fluorescence turn-on ratio (up to 112-fold) in acetonitrile/PBS
      (1:1). Highly efficient photoactivation of the taxoid-tetrazoles inside the
      mammalian cells was also observed under a confocal fluorescence microscope when
      the treated cells were exposed to either a metal halide lamp light passing
      through a 300/395 filter or a 405 nm laser beam. Furthermore, a spatially
      controlled fluorescent labeling of microtubules in live CHO cells was
      demonstrated with a long-wavelength photoactivatable taxoid-tetrazole probe.
      Because of its modular design and tunability of the photoactivation efficiency
      and photophysical properties, this intramolecular photoclick reaction based
      approach should provide a versatile platform for designing photoactivatable
      fluorescent probes for various biological processes.

PMID- 21736330
TI  - Antifouling ultrafiltration membranes via post-fabrication grafting of biocidal
      nanomaterials.
AB  - Ultrafiltration (UF) membranes perform critical pre-treatment functions in
      advanced water treatment processes. In operational systems, however, biofouling
      decreases membrane performance and increases the frequency and cost of chemical
      cleaning. The present work demonstrates a novel technique for covalently or
      ionically tethering antimicrobial nanoparticles to the surface of UF membranes.
      Silver nanoparticles (AgNPs) encapsulated in positively charged polyethyleneimine
      (PEI) were reacted with an oxygen plasma modified polysulfone UF membrane with
      and without 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)
      present. The nucleophilic primary amines of the PEI react with the electrophilic
      carboxyl groups on the UF membrane surface to form electrostatic and covalent
      bonds. The irreversible modification process imparts significant antimicrobial
      activity to the membrane surface. Post-synthesis functionalization methods, such
      as the one presented here, maximize the density of nanomaterials at the membrane
      surface and may provide a more efficient route for fabricating diverse array of
      reactive nanocomposite membranes.

PMID- 21736331
TI  - Gas-phase formaldehyde adsorption isotherm studies on activated carbon:
      correlations of adsorption capacity to surface functional group density.
AB  - Formaldehyde (HCHO) adsorption isotherms were developed for the first time on
      three activated carbons representing one activated carbon fiber (ACF) cloth, one
      all-purpose granular activated carbon (GAC), and one GAC commercially promoted
      for gas-phase HCHO removal. The three activated carbons were evaluated for HCHO
      removal in the low-ppm(v) range and for water vapor adsorption from relative
      pressures of 0.1-0.9 at 26  degrees C where, according to the IUPAC isotherm
      classification system, the adsorption isotherms observed exhibited Type V
      behavior. A Type V adsorption isotherm model recently proposed by Qi and LeVan (Q
      L) was selected to model the observed adsorption behavior because it reduces to a
      finite, nonzero limit at low partial pressures and it describes the entire range
      of adsorption considered in this study. The Q-L model was applied to a polar
      organic adsorbate to fit HCHO adsorption isotherms for the three activated
      carbons. The physical and chemical characteristics of the activated carbon
      surfaces were characterized using nitrogen adsorption isotherms, X-ray
      photoelectron spectroscopy (XPS), and Boehm titrations. At low concentrations,
      HCHO adsorption capacity was most strongly related to the density of basic
      surface functional groups (SFGs), while water vapor adsorption was most strongly
      influenced by the density of acidic SFGs.

PMID- 21736332
TI  - Acceleration of nonylphenol and 4-tert-octylphenol degradation in sediment by
      Phragmites australis and associated rhizosphere bacteria.
AB  - We investigated biodegradation of technical nonylphenol (tNP) in Phragmites
      australis rhizosphere sediment by conducting degradation experiments using
      sediments spiked with tNP. Accelerated tNP removal was observed in P. australis
      rhizosphere sediment, whereas tNP persisted in unvegetated sediment without
      plants and in autoclaved sediment with sterile plants, suggesting that the
      accelerated tNP removal resulted largely from tNP biodegradation by rhizosphere
      bacteria. Three bacterial strains, Stenotrophomonas sp. strain IT-1 and
      Sphingobium spp. strains IT-4 and IT-5, isolated from the rhizosphere were
      capable of utilizing tNP and 4-tert-octylphenol as a sole carbon source via type
      II ipso-substitution. Oxygen from P. australis roots, by creating highly
      oxygenated conditions in the sediment, stimulated cell growth and the tNP
      degrading activity of the three strains. Moreover, organic compounds from P.
      australis roots functioned as carbon and energy sources for two strains, IT-4 and
      IT-5, supporting cell growth and tNP-degrading activity. Thus, P. australis roots
      elevated the cell growth and tNP-degrading activity of the three bacterial
      strains, leading to accelerated tNP removal. These results demonstrate that
      rhizoremediation of tNP-contaminated sediments using P. australis can be an
      effective strategy.

PMID- 21736333
TI  - Genetically encoded 1,2-aminothiols facilitate rapid and site-specific protein
      labeling via a bio-orthogonal cyanobenzothiazole condensation.
AB  - We report evolved orthogonal pyrrolysyl-tRNA synthetase/tRNA(CUA) pairs that
      direct the efficient, site-specific incorporation of N(epsilon)-L-thiaprolyl-L
      lysine, N(epsilon)-D-cysteinyl-L-lysine, and N(epsilon)-L-cysteinyl-L-lysine into
      recombinant proteins in Escherichia coli . We demonstrate that the unique 1,2
      aminothiol introduced by our approach can be efficiently, rapidly, and
      specifically labeled via a cyanobenzothiazole condensation to quantitatively
      introduce biophysical probes into proteins. Moreover, we show that, in
      combination with cysteine labeling, this approach allows the dual labeling of
      proteins with distinct probes at two distinct, genetically defined sites.

PMID- 21736335
TI  - Temperature effect on the structure and formation kinetics of
      vinyltriethoxysilane-derived organic/silica hybrids.
AB  - The structure and formation kinetics of organic/silica hybrid species prepared
      from acid hydrolysis of vinyltriethoxisilane has been studied in situ by small
      angle X-ray scattering (SAXS) at 298, 318, and 333 K in a strongly basic step of
      the process. The evolution of the SAXS intensity is compatible with the formation
      of linear chains which grow, coil, and branch to form polymeric macromolecules in
      solution. The SAXS data were analyzed by the scattering from a persistent chain
      model for polymeric macromolecules in solution using a modified branching Sharp
      and Bloomfield global function, which incorporates a branching probability
      typical of randomly and nonrandomly branched polycondensates, and in a particular
      case, it is also valid for polydisperse coils of linear chains. Growth of linear
      chains and coiling dominate the process up to the formation of likely
      monodisperse Gaussian coils or polydisperse coils of linear chains. The link
      probability to form a branching point is increased with time to form nonrandomly
      branched polycondensates in solution. The kinetics of the process is accelerated
      with temperature, but all the curves formed by the time evolution of the
      structural parameters in all temperatures can correspondingly be matched on a
      unique curve by using an appropriate time scaling factor. The activation energy
      of the process was evaluated as DeltaE = 21 +/- 1 kJ/mol. The characteristics of
      the kinetics are in favor of a complex overall mechanism controlled by both
      condensation reactions and dynamical forces driven by interfacial energy up to
      the final structure development of the hybrids.

PMID- 21736336
TI  - Mechanics and dynamics of the strain-induced M1-M2 structural phase transition in
      individual VO2 nanowires.
AB  - The elastic properties and structural phase transitions of individual VO(2)
      nanowires were studied using an in situ push-to-pull microelectromechanical
      device to realize quantitative tensile analysis in a transmission electron
      microscope and a synchrotron X-ray microdiffraction beamline. A plateau was
      detected in the stress-strain curve, signifying superelasticity of the nanowire
      arising from the M1-M2 structural phase transition. The transition was induced
      and controlled by uniaxial tension. The transition dynamics were characterized by
      a one-dimensionally aligned domain structure with pinning and depinning of the
      domain walls along the nanowire. From the stress-strain dependence the Young's
      moduli of the VO(2) M1 and M2 phases were estimated to be 128 +/- 10 and 156 +/-
      10 GPa, respectively. Single pinning and depinning events of M1-M2 domain wall
      were observed in the superelastic regime, allowing for evaluation of the domain
      wall pinning potential energy. This study demonstrates a new way to investigate
      nanoscale mechanics and dynamics of structural phase transitions in general.

PMID- 21736337
TI  - Optically- and thermally-responsive programmable materials based on carbon
      nanotube-hydrogel polymer composites.
AB  - A simple approach is described to fabricate reversible, thermally- and optically
      responsive actuators utilizing composites of poly(N-isopropylacrylamide) (pNIPAM)
      loaded with single-walled carbon nanotubes. With nanotube loading at
      concentrations of 0.75 mg/mL, we demonstrate up to 5 times enhancement to the
      thermal response time of the nanotube-pNIPAM hydrogel actuators caused by the
      enhanced mass transport of water molecules. Additionally, we demonstrate the
      ability to obtain ultrafast near-infrared optical response in nanotube-pNIPAM
      hydrogels under laser excitation enabled by the strong absorption properties of
      nanotubes. The work opens the framework to design complex and programmable self
      folding materials, such as cubes and flowers, with advanced built-in features,
      including tunable response time as determined by the nanotube loading.

PMID- 21736338
TI  - Interaction of a weakly acidic dinitroaromatic with alkylamines: avoiding the
      Meisenheimer trap.
AB  - Polynitroaromatics are well-known to form anionic sigma-complexes (Meisenheimer
      complexes). The formation of such complexes was assumed in the past to explain
      the blue color of solutions of 2,4-dinitrotoluene (DNT) and amines. However, this
      work shows that caution is warranted to avoid the hasty misidentification of
      Meisenheimer complexes. (1)H NMR spectra exhibit no significant shifts in the
      positions of the DNT protons, indicating that the majority of DNT species in
      solutions of DNT and amines retain their aromaticity. Density functional
      calculations on DNT-ethylamine complexes suggest that Meisenheimer complexes are
      sufficiently high in free energy so that they make up only a very small fraction
      of the full equilibrium population. While principal component analysis of the
      UV/vis spectra of the DNT-amine solutions reveals that only one absorbing species
      of significant concentration is formed, quantitative fits of Job's plots show
      that 1:1 association of DNT with the amines alone cannot explain the visible
      absorption spectra. Instead, the Job's plots can be accurately interpreted by
      deprotonation of DNT, with the amines acting as bases. The deprotonation
      equilibria lie far on the side of the unreacted DNT, preventing the detection by
      NMR of the deprotonated minority species that gives the solutions their strong
      blue color. The analysis of systems with DNT and n-butylamine, diethylamine,
      triethylamine, or benzylamine provides a consistent pK(a) of DNT in dimethyl
      sulfoxide of 15.3 +/- 0.2.

PMID- 21736339
TI  - Atomic-scale mechanical properties of orientated C60 molecules revealed by
      noncontact atomic force microscopy.
AB  - In this work, the mechanical properties of C(60) molecules adsorbed on Cu(111)
      are measured by tuning-fork-based noncontact atomic force microscopy (nc-AFM) and
      spectroscopy at cryogenic conditions. Site-specific tip-sample force variations
      are detected above the buckyball structure. Moreover, high-resolution images
      obtained by nc-AFM show the chemical structure of this molecule and describes
      unambiguously its orientations on the surface.

PMID- 21736340
TI  - Emissions of EC, OC, and PAHs from cottonseed oil biodiesel in a heavy-duty
      diesel engine.
AB  - Biodiesel fuels, made from renewable resources, have emerged as viable
      alternatives to conventional diesel fuel, but their impact on emissions is not
      fully understood. This study examines elemental carbon (EC), organic carbon (OC),
      and polycyclic aromatic hydrocarbons (PAHs) emissions from cottonseed oil
      biodiesel (CSO-B100). Relative to normal diesel fuel, CSO-B100 reduced EC
      emissions by 64% (+/-16%). The bulk of EC emitted from CSO-B100 was in the fine
      particle mode (<1.4 MUm), which is similar to normal diesel. OC was found in all
      size ranges, whereas emissions of OC(1.4-2.5) were proportionately higher in
      OC(2.5) from CSO-B100 than from diesel. The CSO-B100 emission factors derived
      from this study are significantly lower, even without aftertreatment, than the
      China-4 emission standards established in Beijing and Euro-IV diesel engine
      standards. The toxic equivalency factors (TEFs) for CSO-B100 was half the TEFs of
      diesel, which suggests that PAHs emitted from CSO-B100 may be less toxic.

PMID- 21736341
TI  - Boron nitride nanoribbons become metallic.
AB  - Standard spin-polarized density functional theory calculations have been
      conducted to study the electronic structures and magnetic properties of O and S
      functionalized zigzag boron nitride nanoribbons (zBNNRs). Unlike the
      semiconducting and nonmagnetic H edge-terminated zBNNRs, the O edge-terminated
      zBNNRs have two energetically degenerate magnetic ground states with a
      ferrimagnetic character on the B edge, both of which are metallic. In contrast,
      the S edge-terminated zBNNRs are nonmagnetic albeit still metallic. An intriguing
      coexistence of two different Peierls-like distortions is observed for S edge
      termination that manifests as a strong S dimerization at the B zigzag edge and a
      weak S trimerization at the N zigzag edge, dictated by the band fillings at the
      vicinity of the Fermi level. Nevertheless, metallicity is retained along the S
      wire on the N edge due to the partial filling of the band derived from the p(z)
      orbital of S. A second type of functionalization with O or S atoms embedded in
      the center of zBNNRs yields semiconducting features. Detailed examination of both
      types of functionalized zBNNRs reveals that the p orbitals on O or S play a
      crucial role in mediating the electronic structures of the ribbons. We suggest
      that O and S functionalization of zBNNRs may open new routes toward practical
      electronic devices based on boron nitride materials.

PMID- 21736342
TI  - On the regioselectivity of the intramolecular [2 + 2]-photocycloaddition of alk-3
      enyl tetronates.
AB  - The simple diastereoselectivity and the regioselectivity of the [2 + 2]
      photocycloaddition of alk-3-enyl tetronates were studied, depending on the nature
      of the substituent R in the alpha-position. Fourteen tetronates were synthesized
      and their intramolecular photocycloaddition reactions performed. If R was an
      alkoxycarbonyl group and if the olefin, which underwent the intramolecular
      addition, was sterically congested, crossed photoproducts prevailed and were
      formed in yields between 35 and 65%. In all other cases, the straight
      photoproducts were obtained as the main reaction products in yields ranging from
      39 to 84%. The structures of the photochemical products were thoroughly
      investigated by one- and two-dimensional NMR experiments. In all cases, the
      diastereoselectivitiy was excellent and only a single diastereoisomer was formed.
      A mechanistic model is proposed, which explains the regioselectivity of the [2 +
      2]-photocycloaddition reaction.

PMID- 21736343
TI  - Selective modifications of hydrophobic vitamin B12 derivatives at c-and d
      positions.
AB  - The acid-sensitivity of vitamin B(12) derived mono- and diamides was studied. It
      was found that the use of reductive ring-opening of the lactone moiety
      deactivated undesired decomposition of c-mono- and c,d-diamides under acidic
      conditions. As a result, reactions gave respectively c- or d-acids which were
      further functionalized via coupling with amino acids. Though mono- and diamides
      exhibited acid sensitivity, they were used for the preparation of several highly
      functionalized molecules showing their stability under various reaction
      conditions.

PMID- 21736344
TI  - Thermodynamic investigation of the barrier for heterogeneous nucleation on a
      fluid surface in comparison with a rigid surface.
AB  - When a vapor phase is in contact with a solid or nonvolatile fluid, under
      conditions where the vapor is thermodynamically metastable to condensation, a
      droplet may nucleate from the vapor either homogenously within the vapor phase,
      or heterogeneously at the solid or fluid substrate interface. The case where the
      droplet is thermodynamically favored to nucleate heterogeneously is the subject
      of this article. The heterogeneous nucleation of a sessile drop on a soft surface
      has been studied many times experimentally and theoretically. It has been
      observed experimentally that heterogeneous nucleation happens faster on a soft
      surface in comparison with a rigid surface. Here we use Gibbsian surface
      thermodynamics to provide a physical understanding for this observation. Due to
      the difficulties of considering soft-elastic surfaces, we demonstrate that by
      considering only the fluidity of a surface (i.e., by considering a fluid surface
      as an infinitely soft material and comparing a fluid surface with a rigid
      surface), thermodynamics will predict that heterogeneous nucleation is easier on
      soft surfaces compared with rigid surfaces. We first investigate the effect of
      contact angle on the barrier for heterogeneous nucleation on rigid substrates at
      constant vapor phase pressure. Then we find a lower energy barrier for
      heterogeneous nucleation at a fluid surface in comparison with heterogeneous
      nucleation at a rigid surface which explains the faster nucleation on soft
      surfaces compared with rigid surfaces. Finally we inspect the role of each
      contribution to the energy barrier.

PMID- 21736345
TI  - Selective hydrogenolysis of polyols and cyclic ethers over bifunctional surface
      sites on rhodium-rhenium catalysts.
AB  - A ReO(x)-promoted Rh/C catalyst is shown to be selective in the hydrogenolysis of
      secondary C-O bonds for a broad range of cyclic ethers and polyols, these being
      important classes of compounds in biomass-derived feedstocks. Experimentally
      observed reactivity trends, NH(3) temperature-programmed desorption (TPD)
      profiles, and results from theoretical calculations based on density functional
      theory (DFT) are consistent with the hypothesis of a bifunctional catalyst that
      facilitates selective hydrogenolysis of C-O bonds by acid-catalyzed ring-opening
      and dehydration reactions coupled with metal-catalyzed hydrogenation. The
      presence of surface acid sites on 4 wt % Rh-ReO(x)/C (1:0.5) was confirmed by
      NH(3) TPD, and the estimated acid site density and standard enthalpy of NH(3)
      adsorption were 40 MUmol g(-1) and -100 kJ mol(-1), respectively. Results from
      DFT calculations suggest that hydroxyl groups on rhenium atoms associated with
      rhodium are acidic, due to the strong binding of oxygen atoms by rhenium, and
      these groups are likely responsible for proton donation leading to the formation
      of carbenium ion transition states. Accordingly, the observed reactivity trends
      are consistent with the stabilization of resulting carbenium ion structures that
      form upon ring-opening or dehydration. The presence of hydroxyl groups that
      reside alpha to carbon in the C-O bond undergoing scission can form oxocarbenium
      ion intermediates that significantly stabilize the resulting transition states.
      The mechanistic insights from this work may be extended to provide a general
      description of a new class of bifunctional heterogeneous catalysts, based on the
      combination of a highly reducible metal with an oxophilic metal, for the
      selective C-O hydrogenolysis of biomass-derived feedstocks.

PMID- 21736346
TI  - A conserved interdomain interaction is a determinant of folding cooperativity in
      the GST fold.
AB  - The canonical glutathione transferase (GST) fold found in many monomeric and
      dimeric proteins consists of two domains that differ in structure and
      conformational dynamics. However, no evidence exists that the two domains
      unfold/fold independently at equilibrium, indicating the significance of
      interdomain interactions in governing cooperativity between domains.
      Bioinformatics analyses indicate the interdomain interface of the GST fold is
      large, predominantly hydrophobic with a high packing density explaining
      cooperative interdomain behavior. Structural alignments reveal a topologically
      conserved lock-and-key interaction across the domain interface in which a bulky
      hydrophobic residue ("key") protrudes from the surface of the N-domain and
      inserts into a pocket ("lock") in the C-domain. To better understand the
      molecular basis for the contribution of interdomain interactions toward
      cooperativity within the GST fold in the absence of any influence from quaternary
      interactions, studies were done with two monomeric GST proteins: Escherichia coli
      Grx2 (EcGrx2) and human CLIC1 (hCLIC1). Replacing the methionine "key" residue
      with alanine is structurally nondisruptive, whereas it significantly diminishes
      the folding cooperativity of both proteins. The loss in cooperativity between
      domains in the mutants is reflected by a change in the equilibrium folding
      mechanism from a wild-type two-state process to a three-state process, populating
      a stable folding intermediate.

PMID- 21736348
TI  - Doubled power density from salinity gradients at reduced intermembrane distance.
AB  - The mixing of sea and river water can be used as a renewable energy source. The
      Gibbs free energy that is released when salt and fresh water mix can be captured
      in a process called reverse electrodialysis (RED). This research investigates the
      effect of the intermembrane distance and the feedwater flow rate in RED as a
      route to double the power density output. Intermembrane distances of 60, 100,
      200, and 485 MUm were experimentally investigated, using spacers to impose the
      intermembrane distance. The generated (gross) power densities (i.e., generated
      power per membrane area) are larger for smaller intermembrane distances. A
      maximum value of 2.2 W/m(2) is achieved, which is almost double the maximum power
      density reported in previous work. In addition, the energy efficiency is
      significantly higher for smaller intermembrane distances. New improvements need
      to focus on reducing the pressure drop required to pump the feedwater through the
      RED-device using a spacerless design. In that case power outputs of more than 4 W
      per m(2) of membrane area at small intermembrane distances are envisaged.

PMID- 21736347
TI  - Light-induced release of DNA from gold nanoparticles: nanoshells and nanorods.
AB  - Plasmon-resonant nanoparticle complexes show highly promising potential for light
      triggered, remote-controlled delivery of oligonucleotides on demand, for research
      and therapeutic purposes. Here we investigate the light-triggered release of DNA
      from two types of nanoparticle substrates: Au nanoshells and Au nanorods. Both
      light-triggered and thermally induced release are distinctly observable from
      nanoshell-based complexes, with light-triggered release occurring at an ambient
      solution temperature well below the DNA melting temperature. Surprisingly, no
      analogous measurable release was observable from nanorod-based complexes below
      the DNA melting temperature. These results suggest that a nonthermal mechanism
      may play a role in plasmon resonant, light-triggered DNA release.

PMID- 21736349
TI  - Physical properties of thallium-tellurium based thermoelectric compounds using
      first-principles simulations.
AB  - We present a study of the thermodynamic and physical properties of Tl(5)Te(3),
      BiTl(9)Te(6), and SbTl(9)Te(6) compounds by means of density functional theory
      based calculations. The optimized lattice constants of the compounds are in good
      agreement with the experimental data. The electronic density of states and band
      structures are calculated to understand the bonding mechanism in the three
      compounds. The indirect band gaps of BiTl(9)Te(6) and SbTl(9)Te(6) compounds are
      found to be equal to 0.256 and 0.374 eV, respectively. The spin-orbit coupling
      has important effects on the electronic structure of the two semiconducting
      compounds and should therefore be included for a good numerical description of
      these materials. The elastic constants of the three compounds have been
      calculated, and the bulk modulus, shear modulus, and Young's modulus have been
      determined. The change from ductile to brittle behavior after Sb or Bi alloying
      is related to the change of the electronic properties. Finally, the Debye
      temperature and longitudinal, transverse, and average sound velocities have been
      obtained.

PMID- 21736350
TI  - Ligand topology effect on the reactivity of a mononuclear nonheme iron(IV)-oxo
      complex in oxygenation reactions.
AB  - Mononuclear nonheme iron(IV)-oxo complexes with two different topologies, cis
      alpha-[Fe(IV)(O)(BQCN)](2+) and cis-beta-[Fe(IV)(O)(BQCN)](2+), were synthesized
      and characterized with various spectroscopic methods. The effect of ligand
      topology on the reactivities of nonheme iron(IV)-oxo complexes was investigated
      in C-H bond activation and oxygen atom-transfer reactions; cis-alpha
      [Fe(IV)(O)(BQCN)](2+) was more reactive than cis-beta-[Fe(IV)(O)(BQCN)](2+) in
      the oxidation reactions. The reactivity difference between the cis-alpha and cis
      beta isomers of [Fe(IV)(O)(BQCN)](2+) was rationalized with the Fe(IV/III) redox
      potentials of the iron(IV)-oxo complexes: the Fe(IV/III) redox potential of the
      cis-alpha isomer was 0.11 V higher than that of the cis-beta isomer.

PMID- 21736351
TI  - Selective coprecipitation of polyphenols in bioactive/inorganic complexes.
AB  - We investigate the formation of bioactive/inorganic coprecipitates of polyphenols
      catechins with calcium carbonate and calcium phosphate. Extracted from the leaves
      of Camellia sinensis, green tea catechins are efficient free radical scavengers,
      but their purported benefits from the perspective of prevention, health, and
      nutritional physiology are accompanied by unpleasant organoleptic
      characteristics: they are notoriously bitter. Selective complexation of
      polyphenols with metal salts is a possibility to mask or inactivate bitterness
      and/or off-flavors. We produce such complexes using a continuous coprecipitation
      process. With excess calcium chloride present in the matrix we observe a
      correlation of the carbonate to total anions molar ratio with the catechin load.
      To characterize the composition and structure of the coprecipitates we combine
      elemental analysis, scanning electron microscopy, X-ray powder diffraction, and
      liquid chromatography coupled to tandem mass spectroscopy (LC/MS-MS). We quantify
      the release kinetics in different model environments to predict the behavior of
      the catechins from the coprecipitates in model media simulating the conditions
      during oral ingestion and storage. The dissolution data suggest that the release
      profile of these delivery systems can be influenced and fine-tuned via the anion
      composition of the mineral carrier.

PMID- 21736352
TI  - Ultrafast dynamical localization of photoexcited states in conformationally
      disordered poly(p-phenylenevinylene).
AB  - We consider two types of ultrafast dynamical localization of photoexcited states
      in conformationally disordered poly(p-phenylenevinylene). First, we discuss
      nonadiabatic interconversion from higher energy extended exciton states to lower
      energy more localized local exciton ground states. Second, we calculate the
      dynamics of local exciton ground states on their Born-Oppenheimer potential
      energy surfaces. We show that within the first C-C bond oscillation following
      photoexcitation (~35 fs) the exciton becomes self-trapped and localized over
      approximately eight monomers. This process is associated with a Calderia-Leggett
      type loss of phase coherence owing to the coupling of the polymer to a
      dissipative environment. Subsequent torsional relaxation (on a time scale of
      approximately picoseconds) has little effect on the localization. We conclude
      from this that the initial torsional disorder determines the spatial distribution
      and localization length of vertical excitations but that electron-phonon coupling
      is largely responsible for the localization length of self-trapped excitons. We
      next consider the effect of dynamical localization on fluorescence
      depolarization. We show that exciting higher energy states causes a larger
      fluorescence depolarization, because these states have a larger initial
      delocalization. Using the observation that fluorescence depolarization is a
      function of excitation wavelength and polymer conformation, we show how the
      models of exciton localization discussed here can be experimentally investigated.

PMID- 21736353
TI  - Synthesis, characterization, and applications of hemifluorinated dibranched
      amphiphiles.
AB  - Here we describe the synthesis and the physicochemical and preliminary
      pharmaceutical assessment of a novel class of hemifluorinated dibranched
      derivatives: M(1)diH(x)F(y). These compounds have the remarkable ability to
      completely stop the Ostwald ripening commonly associated with nanoemulsions. The
      developed synthesis is modular and allows easy incremental structural variations
      in the fluorophilic (fluorous chains), lipophilic (alkyl spacer head), and
      hydrophilic (polar head) domains. Furthermore, the synthesis can be easily scaled
      up and highly pure compounds can be readily obtained through silica gel and
      fluoro-silica gel column chromatography, without any need to use HPLC or other
      time-consuming techniques. Surface properties such as micelle formation, critical
      aggregation concentration (CAC), and emulsion stability studies demonstrated the
      different behavior of the dibranched hemifluorinated surfactant M(1)diH(x)F(y)
      with respect to that of single-chain semifluorinated analogues M(z)F(y).
      Remarkably, the new polymer M(1)diH(3)F(8) drastically slowed the ripening of
      nanoemulsions of the commonly used fluorinated anesthetic sevoflurane over a
      period of more than 1 year. During this time, the nanodroplet size did not
      increase to more than 400 nm. This result is very promising for inducing and
      maintaining general anesthesia through intravenous delivery of volatile
      anesthetics, eliminating the need for the use of large and costly vaporizers in
      the operating room.

PMID- 21736354
TI  - Physically motivated, robust, ab initio force fields for CO2 and N2.
AB  - We present a novel methodology for developing physically motivated, first
      principles polarizable force fields and apply these techniques to the specific
      cases of CO(2) and N(2). Exchange, electrostatic, induction, and dispersion
      interaction parameters were fit to symmetry adapted perturbation theory (SAPT)
      dimer energy calculations, with explicit terms to account for each of the
      dominant fundamental interactions between molecules. Each term is represented by
      a physically appropriate functional form and fitted individually based on the
      results of the SAPT decomposition. The resulting CO(2) and N(2) force field was
      benchmarked against a diverse set of experimental data, including the second
      virial coefficient, density, scattering structure factor, heat capacity, enthalpy
      of vaporization, and vapor-liquid coexistence curves. In general, excellent
      agreement with experimental data is obtained with our model. Due to the physical
      nature of their construction, these force fields are robust and transferable to
      environments for which they were not specifically parametrized, including gas
      mixtures, and we anticipate applications in modeling CO(2)/N(2) adsorption in
      polar and/or heterogeneous media.

PMID- 21736355
TI  - Mapping of interactions between human macrophages and Staphylococcus aureus
      reveals an involvement of MAP kinase signaling in the host defense.
AB  - Staphylococcus aureus is a dangerous opportunistic human pathogen that causes
      serious invasive diseases when it reaches the bloodstream. Recent studies have
      shown that S. aureus is highly resistant to killing by professional phagocytes
      and that such cells even provide a favorable environment for intracellular
      survival of S. aureus. Importantly, the reciprocal interactions between
      phagocytes and S. aureus have remained largely elusive. Here we have employed
      kinase profiling to define the nature and time resolution of the human THP-1
      macrophage response toward S. aureus and proteomics to identify the response of
      S. aureus toward macrophages. The results of these studies reveal major
      macrophage signaling pathways triggered by S. aureus and proteomic signatures of
      the responses of S. aureus to macrophages. We also identify human proteins bound
      to S. aureus that have potential roles in bacterial killing and internalization.
      Most noticeably, our observations challenge the classical concept that macrophage
      responses are mainly mediated through Toll-like receptor 2 and NF-kappaB
      signaling and highlight the important role of the stress-activated MAP kinase
      signaling in orchestrating the host defense.

PMID- 21736356
TI  - First natural analogs of the cytotoxic thiodepsipeptide thiocoraline A from a
      marine Verrucosispora sp.
AB  - A marine Verrucosispora sp. isolated from the sponge Chondrilla caribensis f.
      caribensis was found to produce thiocoraline, a potent cytotoxic compound. Five
      new analogs of thiocoraline were isolated and represent the first analogs of
      thiocoraline. 22'-Deoxythiocoraline (2), thiochondrilline C (5), and 12'
      sulfoxythiocoraline (6) demonstrated significant cytotoxicity against the A549
      human cancer cell line with EC(50) values of 0.13, 2.86, and 1.26 MUM,
      respectively. The analogs provide insight into the SAR and biosynthesis of
      thiocoraline. The DP4 probability method was used to analyze ab initio NMR
      calculations to confirm stereochemical assignments.

PMID- 21736357
TI  - High-turnover supramolecular catalysis by a protected ruthenium(II) complex in
      aqueous solution.
AB  - The design of a supramolecular catalyst capable of high-turnover catalysis is
      reported. A ruthenium(II) catalyst is incorporated into a water-soluble
      supramolecular assembly, imparting the ability to catalyze allyl alcohol
      isomerization. The catalyst is protected from decomposition by sequestration
      inside the host but retains its catalytic activity with scope governed by
      confinement within the host. This host-guest complex is a uniquely active
      supramolecular catalyst, capable of >1000 turnovers.

PMID- 21736358
TI  - Noncovalent functionalization of carbon nanovectors with an antibody enables
      targeted drug delivery.
AB  - Current chemotherapeutics are characterized by efficient tumor cell-killing and
      severe side effects mostly derived from off-target toxicity. Hence targeted
      delivery of these drugs to tumor cells is actively sought. We previously
      demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are
      able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple
      physisorption and thereby deliver the drug for killing of cancer cells. The cell
      killing when these drug-loaded carbon nanoparticles were used was equivalent to
      when a commercial formulation of paclitaxel was used. Here we show that by
      further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal
      antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel
      is preferentially targeted to EGFR+ tumor cells in vitro. This supports
      progressing to in vivo studies. Moreover, the construct is unusual in that all
      three components are assembled through noncovalent interactions. Such noncovalent
      assembly could enable high-throughput screening of drug/antibody combinations.

PMID- 21736359
TI  - Synthesis of potent and orally efficacious 11beta-hydroxysteroid dehydrogenase
      type 1 inhibitor HSD-016.
AB  - Cortisol and the glucocorticoid receptor (GR) signaling pathway has been linked
      to the development of diabetes and metabolic syndrome. In vivo, 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of
      inactive cortisone to its active form, cortisol. Existing clinical data have
      supported 11beta-HSD1 as a valid therapeutic target for type 2 diabetes. In our
      research program, (R)-1,1,1-trifluoro-2-(3-((R)-4-(4-fluoro-2
      (trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)phenyl)propan-2-ol (HSD
      016) was discovered to be a potent, selective, and efficacious 11beta-HSD1
      inhibitor and advanced as a clinical candidate. Herein, a reliable and scalable
      synthesis of HSD-016 is described. Key transformations include an asymmetric
      synthesis of a chiral tertiary alcohol via Sharpless dihydroxylation, epoxide
      formation, and subsequent mild reduction. This route ensured multikilogram
      quantities of HSD-016 necessary for clinical studies.

PMID- 21736360
TI  - Visible-light-driven copper acetylacetonate decomposition by BiVO4.
AB  - Visible-light irradiation to monoclinic scheelite BiVO(4) (m-BiVO(4)) in a
      solution of copper acetylacetonate (Cu(acac)(2)) has led to its decomposition and
      Cu recovery. The photonic efficiency at lambda = 440 +/- 15 nm reaches 3.4%,
      exceeding the value for the TiO(2)-photocatalyzed reaction at lambda = 355 +/- 23
      nm (2.0%). The adsorption isotherm and the light intensity-dependence of the
      decomposition rate indicate high adsorptivity of m-BiVO(4) for Cu(acac)(2) or its
      sufficient supply to the surface reaction sites, which mainly contributes to the
      high photocatalytic activity. Electrochemical measurements using cyclic
      voltammetry suggest that the reaction proceeds via the oxidative degradation of
      the ligand followed by the reduction of the resulting Cu(2+) ions. Under aerobic
      conditions, the Cu(2+) ions mediate the electron transfer from the conduction
      band of m-BiVO(4) to O(2) to complete the catalytic cycle.

PMID- 21736361
TI  - Differentiating N-terminal aspartic and isoaspartic acid residues in peptides.
AB  - Formation of isoaspartic acid (isoAsp) is a common modification of aspartic acid
      (Asp) or asparagine (Asn) residue in proteins. Differentiation of isoAsp and Asp
      residues is a challenging task owing to their similar properties and identical
      molecular mass. It was recently shown that they can be differentiated using ion
      electron or ion-ion interaction fragmentation methods (ExD) because these methods
      provide diagnostic fragments c + 57 and z(*) - 57 specific to the isoAsp residue.
      To date, however, the presence of such fragments has not been explored on
      peptides with an N-terminal isoAsp residue. To address this question, several N
      terminal isoAsp-containing peptides were analyzed using ExD methods alone or
      combined with chromatography. A diagnostic fragment [M + 2H - 74](+*) was
      observed for the doubly charged precursor ions with N-terminal isoAsp residues.
      For some peptides, identification of the N-terminal isoAsp residue was
      challenging because of the low diagnostic ion peak intensity and the presence of
      interfering peaks. Supplemental activation was used to improve diagnostic ion
      detection. Further, N-terminal acetylation was offered as a means to overcome the
      interference problem by shifting the diagnostic fragment peak to [M + 2H -
      116](+*).

PMID- 21736362
TI  - Striking stability of a substituted silicon(II) bis(trimethylsilyl)amide and the
      facile Si-Me bond cleavage without a transition metal catalyst.
AB  - Silicon(II) bis(trimethylsilyl)amide (LSiN(SiMe(3))(2), L= PhC(NtBu)(2)) (2) has
      been synthesized by the reaction of LSiHCl(2) with KN(SiMe(3))(2) in 1:2 molar
      ratio in high yield where 1 equiv of the latter functions as a
      dehydrochlorinating agent. 2 exhibits a high stability up to 154  degrees C and
      can be handled in open air for a short period of time without any appreciable
      decomposition. An amazing five-membered cyclic silene (3) results from the
      cleavage of one Si-Me bond of 2 with an adamantyl phosphaalkyne. 3 is the first
      example of a heavy cyclopentene derivative which consists of four different
      elements, C, N, Si, and P. Both compounds are characterized by multinuclear NMR
      spectroscopy, EI-mass spectrometry, and single crystal X-ray diffraction studies.

PMID- 21736363
TI  - C-C activation in the solid state in an organometallic sigma-complex.
AB  - Herein is reported the synthesis, by a solid-state reaction from
      [Ir(NBD)(2)(P(i)Pr(3))][BAr(F)(4)], of the first example of a C-C sigma-complex
      with iridium, [Ir(BINOR-S)(P(i)Pr(3))][BAr(F)(4)]. This compound is unique in
      that in the solid state it undergoes reversible activation of the C-C single bond
      that interacts with the metal center, establishing a temperature-dependent
      equilibrium between Ir(III) C-C sigma/Ir(V) bis-alkyl complexes. This process has
      been interrogated by variable-temperature X-ray diffraction, NMR spectroscopy,
      and DFT calculations.

PMID- 21736364
TI  - Evaluating the mixing of organic aerosol components using high-resolution aerosol
      mass spectrometry.
AB  - According to the pseudo-ideal mixing assumption employed in practically all
      chemical transport models, organic aerosol components from different sources
      interact with each other in a single solution, independent of their composition.
      This critical assumption greatly affects modeled organic aerosol concentrations,
      but there is little direct experimental evidence to support it. A main
      experimental challenge is that organic aerosol components from different sources
      often look similar when analyzed with an aerosol mass spectrometer. We developed
      a new experimental method to overcome this challenge, using isotopically labeled
      compounds ((13)C or D) and a high-resolution time-of-flight aerosol mass
      spectrometer (HR-ToF-AMS). We generated mixtures of secondary organic aerosol
      (SOA) from isotopically labeled toluene and from unlabeled alpha-pinene and used
      the HR-ToF-AMS data to separate these different SOA types. We evaluated their
      interaction by comparing the aerosol mass yields of toluene and alpha-pinene when
      the SOA was formed in these mixtures to their yields when the SOA was formed in
      isolation. At equilibrium, our results are consistent with pseudo-ideal mixing of
      anthropogenic and biogenic SOA components from these chemically dissimilar
      precursors.

PMID- 21736365
TI  - Engineering organic sensitizers for iodine-free dye-sensitized solar cells: red
      shifted current response concomitant with attenuated charge recombination.
AB  - With a new metal-free donor-acceptor photosensitizer featuring the 2,6
      bis(thiophen-2-yl)-4,4-dihexyl-4H-cyclopenta[2,1-b:3,4-b']dithiophene-conjugated
      spacer and the tris(1,10-phenanthroline)cobalt(II/III) redox shuttle, we present
      a highly efficient iodine-free dye-sensitized solar cell displaying a power
      conversion efficiency of 9.4% measured at 100 mW cm(-2) simulated AM1.5
      conditions.

PMID- 21736366
TI  - Understanding the preferential adsorption of CO2 over N2 in a flexible metal
      organic framework.
AB  - The unusual uptake behavior and preferential adsorption of CO(2) over N(2) are
      investigated in a flexible metal-organic framework system, Zn(2)(bdc)(2)(bpee),
      where bpdc = 4,4'-biphenyl dicarboxylate and bpee = 1,2-bis(4-pyridyl)ethylene,
      using Raman and IR spectroscopy. The results indicate that the interaction of
      CO(2) with the framework induces a twisting of one of its ligands, which is
      possible because of the type of connectivity of the carboxylate end group of the
      ligand to the metal center and the specific interaction of CO(2) with the
      framework. The flexibility of the bpee pillars allows the structure to respond to
      the twisting, fostering the adsorption of more CO(2). DFT calculations support
      the qualitative picture derived from the experimental analysis. The adsorption
      sites at higher loading have been identified using a modified van der Waals
      Density Functional Theory method, showing that the more energetically favorable
      positions for the CO(2) molecules are closer to the C?C bond of the bpee and the
      C-C bond of the bpdc ligands instead of the benzene and pyridine rings of these
      ligands. These findings are consistent with changes observed using Raman
      spectroscopy, which is useful for detecting both specific guest-host interactions
      and structural changes in the framework.

PMID- 21736367
TI  - Molecular insights into the surface morphology, layering structure, and
      aggregation kinetics of surfactant-stabilized graphene dispersions.
AB  - The production of graphene with open band gaps for the manufacturing of graphene
      based electronic and optical devices requires synthesis methods to either control
      the number of layers to enrich AB-stacked bilayer or trilayer graphene or control
      the extent of functionalization of monolayer graphene. Solution-phase dispersion
      of graphene is promising for both methods to create printable electronics and
      nanocomposites. However, both methods face common challenges, including
      controlling the surface morphology, reducing the turbostratic layering, and
      enhancing the dispersion stability. To address these challenges at the molecular
      level, we successfully combined molecular simulations, theoretical modeling, and
      experimental measurements. First, we probed the surface structure and
      electrostatic potential of monolayer graphene dispersed in a sodium cholate (SC)
      surfactant aqueous solution, which exhibits 2D sheets partially covered with a
      monolayer of negatively charged cholate ions. Similar to the case of carbon
      nanotube functionalization, one may regulate the binding affinity of charged
      reactants for graphene functionalization by manipulating the surface morphology.
      Subsequently, we quantified the interactions between two graphene-surfactant
      assemblies by calculating the potential of mean force (PMF) between two
      surfactant-covered graphene sheets, which confirmed the existence of a metastable
      bilayer graphene structure due to the steric hindrance of the confined surfactant
      molecules. The traditional Derjaguin-Landau-Verwey-Overbeek (DLVO) theory was
      found to be adequate to explain the long-range electrostatic repulsions between
      the ionic surfactant-covered graphene sheets but was unable to account for the
      dominant, short-range steric hindrance imparted by the confined surfactant
      molecules. Interestingly, one faces a dilemma when using surfactants to disperse
      and stabilize graphene in aqueous solution: on the one hand, surfactants can
      stabilize graphene aqueous dispersions, but on the other hand, they prevent the
      formation of new AB-stacked bilayer and trilayer graphene resulting from the
      reaggregation process. Finally, the lifetime and time-dependent distribution of
      various graphene layer types were predicted using a kinetic model of colloid
      aggregation, and each graphene layer type was further decomposed into subtypes,
      including the AB-stacked species and various turbostratic species. The kinetic
      model of colloid aggregation developed here can serve as a useful tool to
      evaluate the quality of graphene dispersions for subsequent substrate
      transferring or functionalization processes.

PMID- 21736368
TI  - Planar tetranuclear Dy(III) single-molecule magnet and its Sm(III), Gd(III), and
      Tb(III) analogues encapsulated by salen-type and beta-diketonate ligands.
AB  - The syntheses, structures, and magnetic properties are reported for four new
      lanthanide clusters [Sm(4)(MU(3)-OH)(2)L(2)(acac)(6)].4H(2)O (1), [Gd(4)(MU(3)
      OH)(2)L(2)(acac)(6)].4CH(3)CN (2), and [Ln(4)(MU(3)
      OH)(2)L(2)(acac)(6)].2H(2)L.2CH(3)CN (3, Ln = Tb; 4, Ln = Dy) supported by salen
      type (H(2)L = N,N'-bis(salicylidene)-1,2-cyclohexanediamine) and beta-diketonate
      (acac = acetylacetonate) ligands. The four clusters were confirmed to be
      essentially isomorphous by infrared spectroscopy and single-crystal X-ray
      diffraction. Their crystal structures reveal that the salen-type ligand provides
      a suitable tetradentate coordination pocket (N(2)O(2)) to encapsulate
      lanthanide(III) ions. Moreover, the planar Ln(4) core is bridged by two MU(3)
      hydroxide, four phenoxide, and two ketonate oxygen atoms. Magnetic properties of
      all four compounds have been investigated using dc and ac susceptibility
      measurements. For 4, the static and dynamic data indicate that the Dy(4) complex
      exhibits slow relaxation of the magnetization below 5 K associated with single
      molecule magnet behavior.

PMID- 21736369
TI  - Third-order nonlinear optical properties of open-shell supermolecular systems
      composed of acetylene linked phenalenyl radicals.
AB  - The third-order nonlinear optical (NLO) properties, at the molecular level, the
      static second hyperpolarizabilities, gamma, of supermolecular systems composed of
      phenalenyl and pyrene rings linked by acetylene units are investigated by
      employing the long-range corrected spin-unrestricted density functional theory,
      LC-UBLYP, method. The phenalenyl based superethylene, superallyl, and
      superbutadiene in their lowest spin states have intermediate diradical characters
      and exhibit larger gamma values than the closed-shell pyrene based superpolyene
      systems. The introduction of a positive charge into the phenalenyl based
      superallyl radical changes the sign of gamma and enhances its amplitude by a
      factor of 35. Although such sign inversion is also observed in the allyl radical
      and cation systems in their ground state equilibrium geometries, the relative
      amplitude of gamma is much different, that is, |gamma(regular allyl
      cation)/gamma(regular allyl radical)| = 0.61 versus |gamma(phenalenyl based
      superallyl cation)/gamma(phenalenyl based superallyl radical)| = 35. In contrast,
      the model ethylene, allyl radical/cation, and butadiene systems with stretched
      carbon-carbon bond lengths (2.0 A), having intermediate diradical characters,
      exhibit similar gamma features to those of the phenalenyl based superpolyene
      systems. This exemplifies that the size dependence of gamma as well as its sign
      change by introducing a positive charge on the phenalenyl based superpolyene
      systems originate from their intermediate diradical characters. In addition, the
      change from the lowest to the highest pi-electron spin states significantly
      reduces the gamma amplitudes of the neutral phenalenyl based superpolyene
      systems. For phenalenyl based superallyl cation, the sign inversion of gamma
      (from negative to positive) is observed upon switching between the singlet and
      triplet states, which is predicted to be associated with a modification of the
      balance between the positive and negative contributions to gamma. The present
      study paves the way toward designing a variety of open-shell NLO supermolecular
      systems composed of phenalenyl radical building blocks.

PMID- 21736370
TI  - Identification and quantification of DNA adducts in the oral tissues of mice
      treated with the environmental carcinogen dibenzo[a,l]pyrene by HPLC-MS/MS.
AB  - Tobacco smoking is one of the leading causes for oral cancer. Dibenzo[a,l]pyrene
      (DB[a,l]P), an environmental pollutant and a tobacco smoke constituent, is the
      most carcinogenic polycyclic aromatic hydrocarbon (PAH) tested to date in several
      animal models (target organs: skin, lung, ovary, and mammary tissues). We have
      recently demonstrated that DB[a,l]P is also capable of inducing oral cancer in
      mice; however, its metabolic activation to the ultimate genotoxic metabolite
      dibenzo[a,l]pyrene-11,12-dihydrodiol-13,14-epoxide (DB[a,l]PDE) in mouse oral
      cavity has not been examined. Here we developed a liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method to detect and quantify (+/-)-anti-DB[a,l]PDE
      dA adducts in oral tissues of mice treated with DB[a,l]P. [(15)N(5)]-(+/-)-anti
      DB[a,l]PDE-N(6)-dA adducts were synthesized as internal standards. The
      stereoisomeric adducts were characterized by MS, NMR, and CD analysis. The
      detection limit of the method is 8 fmol with 100 MUg of digested DNA as the
      matrix. Two adducts were detected and identified as (-)-anti-cis and (-)-anti
      trans-DB[a,l]PDE-dA in the oral tissues of mice following the direct application
      of DB[a,l]P (240 nmol per day, for 2 days) into the oral cavity, indicating that
      DB[a,l]P is predominantly metabolized into (-)-anti-DB[a,l]PDE in this target
      organ. We also compared the formation and removal of adducts as a function of
      time, following the direct application of DB[a,l]P (24 nmol, 3 times per week for
      5 weeks) into the oral cavity of mice. Adducts were quantified at 48 h, 1, 2, and
      4 weeks after the last dose. Maximal levels of adducts occurred at 48 h, followed
      by a gradual decrease. The levels (fmol/MUg DNA) of (-)-anti-trans adducts (4.03
      +/- 0.27 to 1.77 +/- 0.25) are significantly higher than (-)-anti-cis-DB[a,l]PDE
      dA adduct (1.63 +/- 0.42 to 0.72 +/- 0.04) at each time point (p < 0.005). The
      results presented here indicate that the formation and persistence of (-)-anti
      DB[a,l]PDE-dA adducts may, in part, contribute to the initiation of DB[a,l]P
      induced oral carcinogenesis.

PMID- 21736371
TI  - Quantification of primary amine groups available for subsequent
      biofunctionalization of polymer surfaces.
AB  - Biocompatible polymers are commonly functionalized with specific moieties such as
      amino groups to modify their surface properties and/or to attach bioactive
      compounds. A reliable method is usually required to characterize amino group
      surface densities. In this study, aminated polyethylene terephthalate (PET) films
      were generated via an aminolysis reaction involving either ethylenediamine
      molecules (EtDA), in order to vary easily the amino group density on PET
      surfaces, or 25 kDa polyvinylamine (PVAm) as an alternative reagent preventing
      bulk damages resulting from the aminolysis reaction. Among commonly used dyes for
      amino group quantification, Orange II and Coomassie Brillant Blue (CBB) were
      selected to quantify the extent of amine grafting resulting from these
      derivatization procedures. Rapid and convenient colorimetric assays were compared
      to surface atomic compositions obtained from X-ray photoelectron spectroscopy
      (XPS) measurements. Orange II was found to be the most appropriate dye for
      quantifying primary amine groups in a reliable and specific way. Due to its
      unique negative charge and low steric hindrance compared to CBB, the Orange II
      dye was very sensitive and provided reliable quantification over a wide range of
      amino group surface densities (ca. 5 to at least 200 pmol/mm(2)). In order to
      further validate the use of the Orange II dye for amino group quantification, a
      heterobifunctional linker reacting with amino groups was then grafted on modified
      PET surfaces. Interestingly, the good correlation between the densities of
      adsorbed Orange II and covalently grafted linkers suggests that the Orange II
      method is a relevant, reliable, easy, and inexpensive method to predict the
      amount of amino groups available for subsequent functionalization of polymer
      surfaces.

PMID- 21736372
TI  - Permanent inhibition of viral entry by covalent entrapment of HIV gp41 on the
      virus surface.
AB  - HIV entry occurs by concerted conformational changes in the envelope protein
      complex on the surface of the virus. This complex is made up of a trimer of
      heterodimers of two subunits: surface subunit, gp120, and transmembrane subunit,
      gp41. Conformational changes in the envelope complex allow gp41 to mediate
      membrane fusion leading to exposure of two gp41 regions: N-heptad repeat (NHR)
      and C-heptad repeat (CHR). Peptides from the NHR or the CHR have been found to
      inhibit HIV entry. Herein we show that we can covalently inhibit HIV viral entry
      by permanently trapping the gp41 intermediate on the virus surface using a
      covalently reactive group on inhibitory peptides. This is evidence showing that
      vulnerable conformational intermediates exist transiently during HIV viral entry,
      and the details presented herein will facilitate development of envelope as a
      target for therapeutics and potential chemopreventive agents that could disable
      the virus before contact with the host cell.

PMID- 21736373
TI  - Primary structure and phosphorylation of dentin matrix protein 1 (DMP1) and
      dentin phosphophoryn (DPP) uniquely determine their role in biomineralization.
AB  - The SIBLING (small integrin-binding ligand N-linked glycoproteins) family is the
      major group of noncollagenous proteins in bone and dentin. These extremely acidic
      and highly phosphorylated extracellular proteins play critical roles in the
      formation of collagenous mineralized tissues. Whereas the lack of individual
      SIBLINGs causes significant mineralization defects in vivo, none of them led to a
      complete cessation of mineralization suggesting that these proteins have
      overlapping functions. To assess whether different SIBLINGs regulate
      biomineralization in a similar manner and how phosphorylation impacts their
      activity, we studied the effects of two SIBLINGs, dentin matrix protein 1 (DMP1)
      and dentin phosphophoryn (DPP), on mineral morphology and organization in vitro.
      Our results demonstrate distinct differences in the effects of these proteins on
      mineralization. We show that phosphorylation has a profound effect on the
      regulation of mineralization by both proteins. Specifically, both phosphorylated
      proteins facilitated organized mineralization of collagen fibrils and
      phosphorylated DMP1-induced formation of organized mineral bundles in the absence
      of collagen. In summary, these results indicate that the primary structure and
      phosphorylation uniquely determine functions of individual SIBLINGs in regulation
      of mineral morphology and organization.

PMID- 21736374
TI  - Development and application of a phosphoproteomic method using electrostatic
      repulsion-hydrophilic interaction chromatography (ERLIC), IMAC, and LC-MS/MS
      analysis to study Marek's Disease Virus infection.
AB  - Marek's Disease (MD) is an avian neoplastic disease caused by Marek's Disease
      Virus (MDV). The mechanism of virus transition between the lytic and latent cycle
      is still being investigated; however, post-translational modifications,
      especially phosphorylation, have been thought to play an important role.
      Previously, our group has used strong cation exchange chromatography in
      conjunction with reversed-phase liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) to study the changes in global proteomic expression upon MDV infection
      (Ramaroson , M. F.; Ruby, J.; Goshe, M. B.; Liu , H.-C. S. J. Proteome Res. 2008,
      7, 4346-4358). Here, we extend our study by developing an effective separation
      and enrichment approach to investigate the changes occurring in the
      phosphoproteome using electrostatic repulsion-hydrophilic interaction
      chromatography (ERLIC) to fractionate peptides from chicken embryo fibroblast
      (CEF) digests and incorporating a subsequent IMAC enrichment step to selectively
      target phosphorylated peptides for LC-MS/MS analysis. To monitor the
      multidimensional separation between mock- and MDV-infected CEF samples, a casein
      phosphopeptide mixture was used as an internal standard. With LC-MS/MS analysis
      alone, no CEF phosphopeptides were detected, while with ERLIC fractionation only
      1.2% of all identified peptides were phosphorylated. However, the incorporation
      of IMAC enrichment with ERLIC fractionation provided a 50-fold increase in the
      percentage of identified phosphopeptides. Overall, a total of 581 unique
      phosphopeptides were identified (p < 0.05) with those of the MDV-infected CEF
      sample containing nearly twice as many as the mock-infected control of which 11%
      were unique to MDV proteins. The changes in the phosphoproteome are discussed
      including the role that microtubule-associated proteins may play in MDV infection
      mechanisms.

PMID- 21736375
TI  - Interaction of thrombin with sucrose octasulfate.
AB  - The serine protease thrombin plays multiple roles in many important physiological
      processes, especially coagulation, where it functions as both a pro- and
      anticoagulant. The polyanionic glycosaminoglycan heparin modulates thrombin's
      activity through binding at exosite II. Sucrose octasulfate (SOS) is often used
      as a surrogate for heparin, but it is not known whether it is an effective
      heparin mimic in its interaction with thrombin. We have characterized the
      interaction of SOS with thrombin in solution and determined a crystal structure
      of their complex. SOS binds thrombin with a K(d) of ~1.4 MUM, comparable to that
      of the much larger polymeric heparin measured under the same conditions. Nonionic
      (hydrogen bonding) interactions make a larger contribution to thrombin binding of
      SOS than to heparin. SOS binding to exosite II inhibits thrombin's catalytic
      activity with high potency but with low efficacy. Analytical ultracentrifugation
      shows that bovine and human thrombins are monomers in solution in the presence of
      SOS, in contrast to their complexes with heparin, which are dimers. In the X-ray
      crystal structure, two molecules of SOS are bound nonequivalently to exosite II
      portions of a thrombin dimer, in contrast to the 1:2 stoichiometry of the heparin
      thrombin complex, which has a different monomer association mode in the dimer.
      SOS and heparin binding to exosite II of thrombin differ on both chemical and
      structural levels and, perhaps most significantly, in thrombin inhibition. These
      differences may offer paths to the design of more potent exosite II binding,
      allosteric small molecules as modulators of thrombin function.

PMID- 21736376
TI  - Conserved core substructures in the overlay of protein-ligand complexes.
AB  - The method of conserved core substructure matching (CSM) for the overlay of
      protein-ligand complexes is described. The method relies upon distance geometry
      to align structurally similar substructures without regard to sequence similarity
      onto substructures from a reference protein empirically selected to include key
      determinants of binding site location and geometry. The error in ligand position
      is reduced in reoriented ensembles generated with CSM when compared to other
      overlay methods. Since CSM can only succeed when the selected core substructure
      is geometrically conserved, misalignments only rarely occur. The method may be
      applied to reliably overlay large numbers of protein-ligand complexes in a way
      that optimizes ligand position at a specific binding site or subsite or to align
      structures from large and diverse protein families where the conserved binding
      site is localized to only a small portion of either protein. Core substructures
      may be complex and must be chosen with care. We have created a database of
      empirically selected core substructures to demonstrate the utility of CSM
      alignment of ligand binding sites in important drug targets. A Web-based
      interface can be used to apply CSM to align large collections of protein-ligand
      complexes for use in drug design using these substructures or to evaluate the use
      of alternative core substructures that may then be shared with the larger user
      community. Examples show the benefit of CSM in the practice of structure-based
      drug design.

PMID- 21736377
TI  - Vitamin D mushrooms: comparison of the composition of button mushrooms (Agaricus
      bisporus) treated postharvest with UVB light or sunlight.
AB  - This study compared the compositional changes in mushrooms exposed to sunlight
      with those occurring after commercial ultraviolet (UV) light processing. Button
      mushrooms (75 kg) were processed in the presence or absence of UVB light; a third
      group was exposed to direct sunlight. Mushroom composition was evaluated using
      chemical analyses. Vitamin D concentrations were 5, 410, and 374 MUg/100 g (dw)
      in control, UVB, and sunlight groups, respectively. On a dry weight basis, no
      significant changes in vitamin C, folate, vitamins B(6), vitamin B(5),
      riboflavin, niacin, amino acids, fatty acids, ergosterol, or agaritine were
      observed following UVB processing. Sunlight exposure resulted in a 26% loss of
      riboflavin, evidence of folate oxidation, and unexplained increases in ergosterol
      (9.5%). It was concluded that compositional effects of UVB light are limited to
      changes in vitamin D and show no detrimental changes relative to natural sunlight
      exposure and, therefore, provide important information relevant to the
      suitability and safety of UVB light technology for vitamin D enhanced mushrooms.

PMID- 21736378
TI  - Structural role of compensatory amino acid replacements in the alpha-synuclein
      protein.
AB  - A subset of familial Parkinson's disease (PD) cases is associated with the
      presence of disease-causing point mutations in human alpha-synuclein [huAS(wt)],
      including A53T. Surprisingly, the human neurotoxic amino acid 53T is present in
      non-primate, wild-type sequences of alpha-synucleins, including that expressed by
      mice [mAS(wt)]. Because huAS(A53T) causes neurodegeneration when expressed in
      rodents, the amino acid changes between the wild-type human protein [huAS(wt)]
      and mAS(wt) might act as intramolecular suppressors of A53T toxicity in the mouse
      protein, restoring its physiological structure and function. The lack of
      structural information for mAS(wt) in aqueous solution has prompted us to conduct
      a comparative molecular dynamics study of huAS(wt), huAS(A53T), and mAS(wt) in
      water at 300 K. The calculations are based on an ensemble of nuclear magnetic
      resonance-derived huAS(wt) structures. huAS(A53T) turns out to be more flexible
      and less compact than huAS(wt). Its central (NAC) region, involved in fibril
      formation by the protein, is more solvent-exposed than that of the wild-type
      protein, in agreement with nuclear magnetic resonance data. The compactness of
      mAS(wt) is similar to that of the human protein. In addition, its NAC region is
      less solvent-exposed and more rigid than that of huAS(A53T). All of these
      features may be caused by an increase in the level of intramolecular interactions
      on passing from huAS(A53T) to mAS(wt). We conclude that the presence of
      "compensatory replacements" in the mouse protein causes a significant change in
      the protein relative to huAS(A53T), restoring features not too dissimilar to
      those of the human protein.

PMID- 21736379
TI  - Tandem ion trap design with enhanced mass analysis capabilities for large
      populations of ions.
AB  - A new arrangement consisting of two separate radio frequency (rf) quadrupole ion
      traps is used to analyze large populations of ions over a wide mass-to-charge
      (m/z) range. The setup consists of an "accumulation" trap that is maintained at a
      higher pressure than the second high-performance "analyzer" trap. The two traps
      are scanned simultaneously, with a mass difference between that determines the
      residence time and mass range of ions in the analytical trap. Initially, all ions
      are trapped in the accumulation trap and then mass-selectively ejected into the
      analyzer trap. As ions arrive in the analyzer trap, they cool through collisions
      with the buffer gas and then are mass selectively ejected toward the detector.
      This concurrent linked mass scanning reduces the total number of ions present in
      the analyzer trap during mass analysis, thereby reducing space charge effects and
      leading to improved resolution and mass accuracy of analytical spectra.

PMID- 21736380
TI  - Influence of microgel architecture and oil polarity on stabilization of emulsions
      by stimuli-sensitive core-shell poly(N-isopropylacrylamide-co-methacrylic acid)
      microgels: Mickering versus Pickering behavior?
AB  - Charged poly(N-isopropylacrylamide-co-methacrylic acid) [P(NiPAM-co-MAA)]
      microgels can stabilize thermo- and pH-sensitive emulsions. By placing charged
      units at different locations in the microgels and comparing the emulsion
      properties, we demonstrate that their behaviors as emulsion stabilizers are very
      different from molecular surfactants and rigid Pickering stabilizers. The results
      show that the stabilization of the emulsions is independent of electrostatic
      repulsion although the presence and location of charges are relevant. Apparently,
      the charges facilitate emulsion stabilization via the extent of swelling and
      deformability of the microgels. The stabilization of these emulsions is linked to
      the swelling and structure of the microgels at the oil-water interface, which
      depends not only on the presence of charged moieties and on solvent polarity but
      also on the microgel (core-shell) morphology. Therefore, the internal soft and
      porous structure of microgels is important, and these features make microgel
      stabilized emulsions characteristically different from classical, rigid-particle
      stabilized Pickering emulsions, the stability of which depends on the surface
      properties of the particles.

PMID- 21736381
TI  - New way of describing static and dynamic deformations of the Jahn-Teller type in
      ring molecules.
AB  - A new method is presented to describe deformations of an N-membered planar ring
      (N-ring) molecule in terms of deformation vectors that can be expressed by a set
      of 2N-3 deformation amplitudes and phase angles. The deformation coordinates are
      directly derived from the normal vibrational modes of the N-ring and referenced
      to a regular polygon (N-gon) of unit length. They extend the conceptual approach
      of the Cremer-Pople puckering coordinates (J. Am. Chem. Soc. 1975, 97, 1354) to
      the planar ring and make it possible to calculate, e.g., a planar ring of special
      deformation on a Jahn-Teller surface. It is demonstrated that the 2N-3
      deformation parameters are perfectly suited to describe the pseudorotation of a
      bond through the ring as it is found in cyclic Jahn-Teller systems. In general,
      an N-membered planar ring can undergo N-2 different bond pseudorotations provided
      the energetics of such a process is feasible. The Jahn-Teller distortions
      observed in ring compounds correspond either directly to the basic pseudorotation
      modes or to linear combinations of them. Any deformed ring molecule can be
      characterized in terms of the new ring deformation coordinates, which help to
      identify specific electronic effects. The usefulness of the ring deformation
      coordinates is demonstrated by calculating the Jahn-Teller surfaces for bond
      pseudorotation in the case of the cyclopropyl radical cation and cyclobutadiene
      as well as the ring deformation surfaces of disulfur dinitride and its dianion
      employing multireference averaged quadratic coupled cluster (MR-AQCC) theory,
      equation-of-motion coupled cluster theory in form of EOMIP-CCSD, and single
      determinant coupled cluster theory in form of CCSD(T).

PMID- 21736382
TI  - Borane to boryl hydride to borylene dihydride: explicit demonstration of boron-to
      metal alpha-hydride migration in aminoborane activation.
AB  - The sequence of fundamental steps implicit in the conversion of a dihydroborane
      to a metal borylene complex have been elucidated for an [Ir(PMe(3))(3)] system. B
      H oxidative addition has been applied for the first time to an
      aminodihydroborane, H(2)BNR(2), leading to the generation of a rare example of a
      primary boryl complex, L(n)(H)M{B(H)NR(2)}; subsequent conversion to a borylene
      dihydride proceeds via a novel B-to-M alpha-hydride migration. The latter step is
      unprecedented for group 13 ligand systems, and is remarkable in offering alpha-
      substituent migration from a Lewis acidic center as a route to a two-coordinate
      ligand system.

PMID- 21736383
TI  - Aromatic lipophilic spin traps effectively inhibit RPE65 isomerohydrolase
      activity.
AB  - We previously showed that RPE65 does not specifically produce 11-cis-retinol only
      but also 13-cis-retinol, supporting a carbocation or radical cation mechanism of
      isomerization. The intrinsic properties of conjugated polyene chains result in
      facile formation of radical cations in oxidative conditions. We hypothesized that
      such radical intermediates, if involved in the mechanism of RPE65, could be
      stabilized by spin traps. We tested a variety of hydrophilic and lipophilic spin
      traps for their ability to inhibit RPE65 isomerohydrolase activity. We found that
      the aromatic lipophilic spin traps such as N-tert-butyl-alpha-phenylnitrone
      (PBN), 2,2-dimethyl-4-phenyl-2H-imidazole-1-oxide (DMPIO), and nitrosobenzene
      (NB) strongly inhibit RPE65 isomerohydrolase activity in vitro.

PMID- 21736384
TI  - Regioselective functionalization of the thiazole scaffold using TMPMgCl.LiCl and
      TMP2Zn.2MgCl2.2LiCl.
AB  - A general method for the synthesis of 2,4,5-trisubstituted thiazoles has been
      developed. Starting from commercially available 2-bromothiazole, successive
      metalations using TMPMgCl.LiCl or TMP(2)Zn.2MgCl(2).2LiCl lead to the
      corresponding magnesated or zincated thiazoles which readily react with various
      electrophiles providing highly functionalized thiazoles.

PMID- 21736385
TI  - Conjugated-polyelectrolyte-grafted cotton fibers act as "micro flypaper" for the
      removal and destruction of bacteria.
AB  - We demonstrate herein a method for chemically modifying cotton fibers and cotton
      containing fabric with a light-activated, cationic phenylene-ethynylene (PPE
      DABCO) conjugated polyelectrolyte biocide. When challenged with Pseudomonas
      aeruginosa and Bacillus atropheaus vegetative cells from liquid suspension, light
      activated PPE-DABCO effects 1.2 and 8 log, respectively, losses in viability of
      the exposed bacteria. These results suggest that conjugated polyelectrolytes
      retain their activity when grafted to fabrics, showing promise for use in
      settings where antimicrobial textiles are needed.

PMID- 21736386
TI  - Age-associated variation in sensory perception of iron in drinking water and the
      potential for overexposure in the human population.
AB  - Humans interact with their environment through the five senses, but little is
      known about population variability in the ability to assess contaminants. Sensory
      thresholds and biochemical indicators of metallic flavor perception in humans
      were evaluated for ferrous (Fe(2+)) iron in drinking water; subjects aged 19-84
      years participated. Metallic flavor thresholds for individuals and subpopulations
      based on age were determined. Oral lipid oxidation and oral pH were measured in
      saliva as potential biochemical indicators. Individual thresholds were 0.007
      14.14 mg/L Fe(2+) and the overall population threshold was 0.17 mg/L Fe(2+) in
      reagent water. Average thresholds for individuals younger and older than 50 years
      of age (grouped by the daily recommended nutritional guidelines for iron intake)
      were significantly different (p = 0.013); the population thresholds for each
      group were 0.045 mg/L Fe(2+) and 0.498 mg/L Fe(2+), respectively. Many subjects
      >50 and a few subjects <50 years were insensitive to metallic flavor. There was
      no correlation between age, oral lipid oxidation, and oral pH. Standardized
      olfactory assessment found poor sensitivity for Fe(2+) corresponded with
      conditions of mild, moderate, and total anosmia. The findings demonstrate an age
      dependent sensitivity to iron indicating as people age they are less sensitive to
      metallic perception.

PMID- 21736387
TI  - Storage elevates phenolic content and antioxidant activity but suppresses
      antiproliferative and pro-apoptotic properties of colored-flesh potatoes against
      human colon cancer cell lines.
AB  - Colored-flesh potatoes are an excellent source of health-benefiting dietary
      polyphenols, but are stored for up to 3-6 months before consumption. This study
      investigated the effect of simulated commercial storage conditions on antioxidant
      activity (DPPH, ABTS), phenolic content (FCR) and composition (UPLC-MS), and
      anticancer properties (early, HCT-116 and advanced stage, HT-29 human colon
      cancer cell lines) of potato bioactive compounds. Extracts from seven potato
      clones of differing flesh colors (white, yellow, and purple) before and after 90
      days of storage were used in this study. The antioxidant activity of all clones
      increased with storage; however, an increase in total phenolic content was
      observed only in purple-fleshed clones. Advanced purple-fleshed selection CO97227
      2P/PW had greater levels of total phenolics, monomeric anthocyanins, antioxidant
      activity and a diverse anthocyanin composition as compared with Purple Majesty.
      Purple-fleshed potatoes were more potent in suppressing proliferation and
      elevating apoptosis of colon cancer cells compared with white- and yellow-fleshed
      potatoes. The extracts from both fresh and stored potatoes (10-30 MUg/mL)
      suppressed cancer cell proliferation and elevated apoptosis compared with the
      solvent control, but these anticancer effects were more pronounced with the fresh
      potatoes. Storage duration had a strong positive correlation with antioxidant
      activity and percentage of viable cancer cells and a negative correlation with
      apoptosis induction. These results suggest that although the antioxidant activity
      and phenolic content of potatoes were increased with storage, the
      antiproliferative and pro-apoptotic activities were suppressed. Thus, in the
      assessment of the effects of farm to fork operations on the health-benefiting
      properties of plant foods, it is critical to use quantitative analytical
      techniques in conjunction with in vitro and/or in vivo biological assays.

PMID- 21736388
TI  - Antimalarial activity of natural and synthetic prodiginines.
AB  - Prodiginines are a family of linear and cyclic oligopyrrole red-pigmented
      compounds. Herein we describe the in vitro antimalarial activity of four natural
      (IC(50) = 1.7-8.0 nM) and three sets of synthetic prodiginines against Plasmodium
      falciparum. Set 1 compounds replaced the terminal nonalkylated pyrrole ring of
      natural prodiginines and had diminished activity (IC(50) > 2920 nM). Set 2 and
      set 3 prodiginines were monosubstituted or disubstituted at either the 3 or 5
      position of the right-hand terminal pyrrole, respectively. Potent in vitro
      activity (IC(50) = 0.9-16.0 nM) was observed using alkyl or aryl substituents.
      Metacycloprodiginine and more potent synthetic analogues were evaluated in a P.
      yoelii murine patent infection using oral administration. Each analogue reduced
      parasitemia by more than 90% after 25 (mg/kg)/day dosing and in some cases
      provided a cure. The most favorable profile was 92% parasite reduction at 5
      (mg/kg)/day, and 100% reduction at 25 (mg/kg)/day without any evident weight
      loses or clinical overt toxicity.

PMID- 21736390
TI  - A steroid-conjugated magnetic resonance probe enhances contrast in progesterone
      receptor expressing organs and tumors in vivo.
AB  - Progesterone receptor (PR) is a significant biomarker in diseases such as
      endometriosis and breast, ovarian, and uterine cancers that is associated with
      disease prognosis and therapeutic efficacy. While receptor status is currently
      determined by immunohistochemistry assays, the development of noninvasive PR
      imaging agents could improve molecular characterization, treatment decisions, and
      disease monitoring. ProGlo, a progesterone-conjugated magnetic resonance imaging
      (MRI) contrast agent, was evaluated in vivo to determine whether it targets and
      enhances signal intensity in organs and tumors that express high PR levels. A
      tissue distribution study indicated that ProGlo accumulates in the PR-rich
      uterus, which was confirmed by in vivo imaging studies. Ex vivo images of these
      organs revealed that ProGlo was distributed in the substructures that express
      high PR levels. In xenograft tumor models, ProGlo was taken up to a greater
      extent than the nonfunctionalized Gd-DO3A in tumors, particularly in PR(+)
      tumors. The ability to accumulate and enhance signal intensity in PR(+) organs
      and tumors suggests that ProGlo may be a promising MRI probe for PR(+) diseases.

PMID- 21736391
TI  - Development of a novel proteomic approach for mitochondrial proteomics from
      cardiac tissue from patients with atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting
      approximately 2.2 million Americans. Because several studies have suggested that
      changes in mitochondrial function and morphology may contribute to AF, we
      developed a novel proteomic workflow focused on the identification of
      differentially expressed mitochondrial proteins in AF patients. Right human
      atrial tissue was collected from 20 patients, 10 with and 10 without AF, and the
      tissue was subjected to hydrostatic pressure cycling-based lysis followed by
      label-free mass spectrometric (MS) analysis of mitochondrial enriched isolates.
      Approximately 5% of the 700 proteins identified by MS analysis were
      differentially expressed between the AF and non-AF samples. We chose four
      differentially abundant proteins for further verification using reverse phase
      protein microarray analysis based on their known importance in energy production
      and regulatory association with atrial ion channels: four and a half LIM,
      destrin, heat shock protein 2, and chaperonin-containing TCP1. These initial
      study results provide evidence that a workflow to identify AF-related proteins
      that combines a powerful upfront tissue cell lysis with high resolution MS for
      discovery and protein array technology for verification may be an effective
      strategy for discovering candidate markers in highly fibrous tissue samples.

PMID- 21736392
TI  - Value-based pricing: incentive for innovation or zero net benefit?

PMID- 21736393
TI  - Colorectal cancer mortality trends in Spain. What shall we do?

PMID- 21736394
TI  - Study of colorectal mortality in the Andalusian population.
AB  - OBJECTIVES: to provide up-to-date information and to analyze recent changes in
      colorectal cancer mortality trends in Andalusia during the period of 1980-2008
      using joinpoint regression models. PATIENTS AND METHODS: age- and sex-specific
      colorectal cancer deaths were taken from the official vital statistics published
      by the Instituto de Estadistica de Andalucia for the years 1980 to 2008. We
      computed age-specific rates for each 5-year age group and calendar year and age
      standardized mortality rates per 100,000 men and women. A joinpoint regression
      analysis was used for trend analysis of standardized rates. Joinpoint regression
      analysis was used to identify the years when a significant change in the linear
      slope of the temporal trend occurred. The best fitting points (the "join-points")
      are chosen where the rate significantly changes. RESULTS: mortality from
      colorectal cancer in Andalusia during the period studied has increased, from 277
      deaths in 1980 to 1,227 in 2008 in men, and from 333 to 805 deaths in women.
      Adjusted overall colorectal cancer mortality rates increased from 7.7 to 17.0
      deaths per 100,000 person-years in men and from 6.6 to 9.0 per 100,000 person
      years in women Changes in mortality did not evolve similarly for men and women.
      Age-specific CRC mortality rates are lower in women than in men, which imply that
      women reach comparable levels of colorectal cancer mortality at higher ages than
      men. CONCLUSIONS: sex differences for colorectal cancer mortality have been
      widening in the last decade in Andalusia. In spite of the decreasing trends in
      age-adjusted mortality rates in women, incidence rates and the absolute numbers
      of deaths are still increasing, largely because of the aging of the population.
      Consequently, colorectal cancer still has a large impact on health care services,
      and this impact will continue to increase for many more years.

PMID- 21736395
TI  - Efficacy of adalimumab in patients with Crohn's disease and failure to infliximab
      therapy: a clinical series.
AB  - BACKGROUND: adalimumab, a human anti-TNF, is an effective induction and
      maintenance therapy for patients with moderate to severe Crohn's disease. It
      seems to be effective in patients with resistance to infliximab, too, though the
      experience is more limited. AIM: to evaluate the efficacy of adalimumab, in
      patients with Crohn's disease (CD) and failure to previous treatment with
      infliximab. METHODS: twenty-five patients with CD and failure to previous
      treatment with infliximab were enrolled; they were treated with 160/80 (24
      patients) and 80/40 (1 patient) induction doses. We analyze clinical response to
      treatment with adalimumab by the Crohn's disease Activity Index (CDAI) and plasma
      concentration of C-reactive protein (CRP), steroid sparing and complete fistula
      closure at week 48. RESULTS: eighteen out of twenty-five patients (72%) achieved
      clinical remission (CDAI score < 150) at week 24 and 15/25 (60%) patients at week
      48. There was a statistically significant difference(p < 0.01) in CRP serum
      levels from 21 to 8 mg/dl at week 48.Nine out of fifteen patients (60%) treated
      with corticosteroids were able to discontinue steroids. Three out of eleven
      patients (27%) with fistulizing Crohn's disease had complete fistula closure
      after the treatment. Seventy two percent of the patients (18/25) needed to
      increase adalimumab to weekly dose, in order to maintain clinical response. Five
      out of twenty-five patients (20%) had adverse events; two of them (8%) with
      serious adverse events (tuberculous meningitis and abdominal abscess) that forced
      the withdrawal of treatment. CONCLUSIONS: according to these data, adalimumab
      provides a clinical and analytical improvement in patients with CD and failure to
      previous therapy with infliximab.

PMID- 21736396
TI  - Predictive ultrasound factors of lymphatic invasion in rectal cancer: "extra
      corporeal" study.
AB  - OBJECTIVE: the accuracy of preoperative endorectal ultrasound in the status
      evaluation of lymph nodes is around 50-70%, with a lack of eco-morphological
      patterns of clinical use. Since, accurate local staging is of great value in
      prognosis and decision-making we decided to analyze the referenced eco
      morphological parameters in a try to find a proper predictive tool of clinical
      help that could improve the accuracy of rectal ultrasound. MATERIAL AND METHOD:
      the resected specimens of 24 patients that were operated on by radical surgery
      because rectal cancer, without preoperative radiotherapy were suspended in warm
      water and ultrasound scanned (360o circular probe with a transducer of 10 Mhz).
      All suspicious nodes were recorded and marked for the definitive histological
      report. RESULTS: from the 24 specimens, 318 nodes were imaged(210 benign and 100
      involved). All ultrasound parameters analysed were significant but only
      lobulation, echogenicity and hilar reflection were independent values. An score
      system was design with the addition of all parameters that showed a sensitivity
      of 98%and specificity of 99,1%. CONCLUSIONS: our study shows that a careful study
      of ultra-sound lymph node images can get a high level of accuracy and better help
      in tailoring the treatment of any particular case.

PMID- 21736397
TI  - Does correlation exist between anorectal manometry and endoanal ultrasound
      findings in healthy subjects according to age?
AB  - BACKGROUND: different studies have demonstrated the correlation between anorectal
      manometry and endoanal ultrasonography data in patients with fecal incontinence,
      but there is no almost interest describing the same in healthy subjects according
      to age. AIMS: to study the possible correlation between anorectal manometry and
      endoanal ultrasonography data in a homogeneous group of healthy women, also
      according to age. MATERIAL AND METHODS: prospective observational study of a
      healthy subjects cohort (n=14). Homogeneous group of healthy volunteer women
      divided in 2 subgroups according to age. RESULTS: there was no proved correlation
      between the internal anal sphincter's measurement and the resting pressure in the
      whole sample as well as the analysis according to age. Neither there was any
      proved statistically significant correlation between the external anal
      sphincter's thickness and the squeeze pressure, in the whole sample and by
      groups. CONCLUSIONS: it does not exist statistically significant correlation
      between the thickness of the sphincters and its function in a healthy subjects
      homogeneous group, neither in 2 groups according to age.

PMID- 21736398
TI  - Molecular targets in the design of antifibrotic therapy in chronic liver disease.

PMID- 21736399
TI  - Endoscopic image of an ileo-colonic intussusception.

PMID- 21736400
TI  - Telangiectasias bleeding in patient with systemic sclerosis [correction of
      multiple sclerosis].

PMID- 21736401
TI  - Percutaneous endoscopic suturing is an alternative treatment for persistent
      gastrocutaneous post-PEG fistula.
AB  - Persistent gastrocutaneous fistula after the removal of a gastrostomy tube is an
      unusual complication associated with percutaneous endoscopic gastrostomy (PEG).
      Surgical closure has been usually the treatment of choice. Several endoscopic
      methods have been previously attempted to close the fistula, usually with poor
      results. We report a successful case of percutaneous endoscopic suturing of a
      persistent gastrocutaneous post-PEG fistula, using a monofilament absorbable
      suture. A biopsy forceps was used to deepithelialize both ends of the fistulous
      tract to promote granulation tissue formation. The gastrocutaneous fistula closed
      completely after the procedure and there were no complications during the follow
      up.

PMID- 21736402
TI  - [ Patient information. Megaloblastic anemia and atrophic gastritis].

PMID- 21736403
TI  - Endoscopic extraction of a pig-tail catheter after urological surgery with Mainz
      II pouch urinary diversion.

PMID- 21736404
TI  - Foreign bodies as infrequent cause of liver abscess.

PMID- 21736405
TI  - The medullary carcinoma of the pancreas. A relative new entity.

PMID- 21736406
TI  - Primary carcinosarcoma of the liver: an unusual case with clearly separated
      epithelial and mesenchymal components.

PMID- 21736407
TI  - Esophageal stenosis caused by alendronate.

PMID- 21736408
TI  - Lynch syndrome-associated kidney cancer.

PMID- 21736409
TI  - Influence of coconut oil administration on some hematologic and metabolic
      parameters in pregnant rats.
AB  - OBJECTIVE: Data on the effect of coconut oil intake on various hematologic and
      metabolic parameters in pregnant women or animals are scanty. Hence we attempted
      to assess the effect of oral administration of graded doses of this edible oil
      during pregnancy, on various hematologic and metabolic parameters in rats.
      METHODS: Groups of pregnant Sprague Dawley rats were given oral doses of 1 ml, 2
      ml, and 4 ml coconut oil twice per day, respectively. Control group of rats were
      given tap water. Oral feeding of oil was done continuously for a period of 20
      days and at the end of the study period the animals were lightly anaesthetized
      with ether and sacrificed to collect blood samples for analysis. Various
      hematologic parameters such as red blood cell (RBC) count, white blood cell (WBC)
      count, hemoglobin (Hg), platelets, lymphocytes, and mean corpuscular hemoglobin
      concentration (MCHC) were analyzed by a hematology blood analyzer, while
      metabolic parameters such as cholesterol, triglycerides, urea, uric acid,
      creatinine, and protein were analyzed by specific analytical kits. Activities of
      antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPX), and
      total antioxidant activity (TAO) were assessed by specific analytical kits.
      Statistical analysis of data was performed using a SPSS data analytical package.
      RESULTS: Oral administration of coconut oil for 20 continuous days of pregnancy
      did not significantly alter any of the hematologic parameters studied, compared
      to control group even when the oil was administered at a relatively massive dose
      of 4 ml/day. Administration of coconut oil appeared to decrease WBC, Hg,
      platelet, and lymphocyte blood concentrations in treated rats, but the
      difference, however, was not statistically significant (ANOVA test; p > 0.05).
      However, platelet concentration was significantly lower (p < 0.05) in rats
      receiving 1 ml/day of coconut oil compared to control group rats. Administration
      of coconut oil did not alter the concentrations of protein, cholesterol, urea,
      triglycerides, uric acid, and creatinine in treated groups of rats significantly
      (Student's t-test, p > 0.05) compared to those of control rats. SOD, GPX, and TAO
      levels in control and treated groups were not significantly different (ANOVA
      test, p > 0.05) than controls. CONCLUSIONS: We conclude that oral administration
      of coconut oil during pregnancy in rats, even in massive doses, does not cause
      any significant alterations in hematologic and metabolic parameters. More
      detailed studies, however, are warranted before extrapolating these results to
      human situations.

PMID- 21736411
TI  - Menninger faces the 21st century.
AB  - The origin of the Menninger Clinic and Foundation stems from the vision of a
      family practitioner in a small midwestern community in the early 1900s,
      implemented with the participation of two sons who became psychiatrists. They
      articulated their hopes for the future of the institution in 1953, which surfaced
      only after the passing of the last founder in 1990. At that time, trends in
      healthcare financing were challenging the capacity of the institution they
      founded to fulfill its stated mission. This article reviews the origins and
      mission of Menninger, the challenges prompting a reassessment of operations and
      the search for an affiliate in order to fulfill the full institutional mission.
      Also cited are some principles for the future, and the impact on the midwestern
      community.

PMID- 21736412
TI  - The tangled trail from Topeka to Houston: the Menninger Clinic-mid-1999 to mid
      2003: a personal recollection.
AB  - This article traces many of the key events during the move of the Menninger
      Clinic from Topeka, Kansas, to Houston, Texas, and the affiliation with the
      Baylor College of Medicine and the Methodist Hospital in Houston. It is based on
      the personal recollections of John McKelvey, who was involved, in some form, in
      almost all aspects of the decision to move, the selection of the Houston
      location, the affiliation negotiations, and the final implementation of the
      relocation.

PMID- 21736413
TI  - Transplanting an organization: how does culture matter.
AB  - Cultural differences are often cited as a major obstacle to the successful
      transition/integration into new situations of organizations. In this
      contribution, the author details the changing cultural factors impacting the
      operation and move of the Menninger Clinic from autonomous status to an
      affiliation with and first year of operation in the Baylor College of Medicine
      and Methodist Hospital Health Care System. Both functional and dysfunctional
      consequences are outlined, and specific examples illustrate how the
      organization's leadership and staff struggled to adapt during this complicated
      process. Based on the experience within the Clinic, general recommendations for
      managing such an acculturation are provided.

PMID- 21736414
TI  - Relocating the Menninger Hospital: a nursing perspective.
AB  - The move of the Menninger Hospital represented a special challenge to the direct
      care nursing staff. As the efforts to implement an effective translocation of the
      clinical services moved forward, the goal included an effective transfer of the
      long-established therapeutic community and practices of Menninger into the new
      setting. This article reviews the challenges, processes, and problems in
      achieving that goal.

PMID- 21736415
TI  - How to move a psychiatric facility.
AB  - A special challenge for the transition of Menninger/Kansas to Menninger/Texas was
      the preparation of suitable facilities for the relocated operations in Houston.
      The vice president of Facilities & Property Management recounts the tasks that
      were his responsibility and the process he went through to assure a successful
      move not only to Houston, but also within Houston planning for two major moves in
      less than a decade, an unprecedented challenge.

PMID- 21736416
TI  - Menninger: renewing the vision of success.
AB  - Organizations without vision struggle to find hope and remain mere organizations,
      surviving but not living, hitting temporary targets, but not moving toward their
      potential.

PMID- 21736417
TI  - Preserving hope.
AB  - The author proposes that the ongoing success of the relocation of The Menninger
      Clinic from Kansas to Texas hinges on maintaining a balance between conservation
      and innovation. Focusing on the conservation side of this balance, the author
      highlights two concepts, one of which is ostensibly new: mentalizing, that is,
      attending to mental states in others and oneself-in short, holding mind in mind.
      Although there is much innovative research on mentalizing, particularly in its
      relation to attachment theory, much is conservative: Our focus on mentalizing
      sustains the psychotherapeutic culture. The other concept is ancient but
      typically more implicit than explicit in our work: hope. The author endeavors to
      help us hold in mind Karl Menninger and Paul Pruyser's lasting contributions to
      understanding and cultivating hope. Notably, these seemingly disparate concepts,
      mentalizing and hope, are intimately connected: Both are founded in trust.

PMID- 21736418
TI  - A preliminary investigation of the utility of the "Behavior Support Plan Quality
      Evaluation Guide II" for use in Australia.
AB  - BACKGROUND: The quality of behaviour support plans (BSPs) can be an important
      influence on the quality of the support provided to people with disability who
      show challenging behaviours. The Behavior Support Plan Quality Evaluation Guide
      II (BSP-QE II) is one tool that may be useful in assessing the quality of
      behaviour support plans. It has previously been used to assess BSPs to support
      children in schools in the USA. In this preliminary study, we examined the
      utility of the BSP-QE II for assessing behaviour support plans designed for
      adults with an intellectual disability in community support services in
      Australia. METHOD: Experienced practitioners were surveyed concerning the
      relevance of BSP-QE II components to the evaluation of BSPs in Australia, and an
      audit was conducted of randomly selected BSPs submitted as a statutory
      requirement to the Office of the Senior Practitioner. RESULTS: The BSP-QE II
      showed evidence of acceptable construct validity and interrater reliability.
      There was evidence of a need for substantial improvement in the quality of BSPs,
      consistent with previous findings conducted using other audit tools. CONCLUSIONS:
      The findings support the utility of the BSP-QE II, to inform and evaluate service
      planning in supporting adults with intellectual disability who show challenging
      behaviour.

PMID- 21736419
TI  - Platelet proteome in healthy volunteers who smoke.
AB  - Smoking accelerates atherosclerosis and is a well-known risk factor for acute
      cardiovascular complications; however, the mechanisms of these effects have not
      been completely clarified. Recently developed proteomic approaches may offer new
      clues when combined with well-established functional tests. Platelet proteome of
      healthy smokers and non-smokers was resolved by two-dimensional difference gel
      electrophoresis, compared by Decyder software and identified by mass spectrometry
      analysis (nano-LC-MS/MS). In smokers, three proteins (Factor XIII-A subunit,
      platelet glycoprotein IIb and beta-actin) were significantly up-regulated,
      whereas WDR1 protein and chaperonine HSP60 were down-regulated. Furthermore, the
      highest scored network derived by Ingenuity Pathway Analysis using the modulated
      proteins as input showed the involvement of several proteins to be related to
      inflammation and apoptosis. Platelet function tests and the levels of markers of
      platelet and leukocyte activation were not different in smokers vs. non-smoker
      subjects. The platelet proteomic approach confirms that cigarette smoking
      triggers several inflammatory reactions and may help clarify some of the
      molecular mechanisms of smoke effect on cellular systems relevant for vascular
      integrity and human health.

PMID- 21736420
TI  - The relationship of platelet count, mean platelet volume with metabolic syndrome
      according to the criteria of the American Association of Clinical
      Endocrinologists: a focus on gender differences.
AB  - Metabolic syndrome (MS) is becoming globally prevalent and it is clinically
      important because of its association with type 2 diabetes and cardiovascular
      disease, and some cancers. Recently, platelet count has been linked to insulin
      resistance and MS in addition to being a marker of hemostasis. Also, mean
      platelet volume (MPV) has been known to represent platelet activity. Platelet
      counts and MPV are modified by various biosocial and lifestyle factors such as
      race, age, gender, smoking habit, alcohol consumption, and physical activity.
      Thus, the direction and magnitude of this association may differ by gender. In
      this regard, proper interpretion of platelet counts and MPV by gender could be
      important in the people with MS. We examined the relationship between platelet
      counts, MPV, and MS through gender-specific analyses for 3827 Korean adults (2169
      men and 1658 women) in a health examination program. In women, platelet counts
      were significantly higher in subjects with MS compared to in those without MS (p
      < 0.001), whereas MPV was significantly lower (p = 0.001). However, no such trend
      was observed in men. Multiple regression analyses also showed that MS is
      positively associated with platelet counts and inversely associated with MPV,
      independently of confounding variables only in women. The results suggest that
      platelet counts and MPV might be a surrogate marker associated with clustered MS
      in women.

PMID- 21736421
TI  - Periodic acid-Schiff (PAS) staining of immature platelets in donors.
AB  - Glycogen in platelets (PLTs) on smears of peripheral blood of 40 donors was
      investigated by the periodic acid-Schiff (PAS) method. Three groups were formed.
      Group 1 was consisted of 21 men undergoing the donor selection procedure.
      Additionally, 9 first-time donors undergoing plateletpheresis (Group 2) and 10
      donors who frequently underwent platelet apheresis (Group 3) were studied as a
      model of relative thrombocytopenia. Cell sizes were measured with the use of a
      Image Analyzer "ASPBC" (Russia). The training procedure and classification of PAS
      blood PLTs were made on the basis of expert evaluation. In this article, we have
      established three facts. First, the PAS-positive PLT area was larger than that of
      the PAS-negative cells (9.5 +/- 3.6 sq.mkm vs. 3.9 +/- 1.3 sq.mkm, p < 0.001, n =
      21). The PAS-positivity of PLTs was 23.1 +/- 9.2%. Second, the PAS-positivity
      correlated (r(S) = 0.63, p < 0.05) with the immature platelets fraction (IPF %),
      determined using Sysmex XE-2100. The mean IPF was 2.1 +/- 1.0% (range 0.3-4.6%).
      Third, using the IPF% values obtained in Group 1, we found a significantly higher
      level of IPF in the samples both in Group 2 [mean value 4.2 +/- 2.0% (range 1.9
      7.0), p < 0.01] and in Group 3 [mean value 5.1 +/- 2.5% (range 1.2-8.6), p <
      0.004] with relative thrombocytopenia [Group 2: median 198 (95% confidence
      interval, CI 166-227) vs. median 229 (95% CI 206-267), p < 0.05; Group 3: median
      142.5 (95% CI 132-173) vs. median 214.5 (95% CI 196-267), p < 0.01] after
      plateletpheresis. There was also a significant difference between the pre- and
      post-plateletpheresis for IPF% in Group 2 and Group 3: median 1.7 (95% CI 1.4
      4.0) vs. median 4.0 (95% CI 2.7-5.8), p < 0.05 and median 4.0 (95% CI 2.7-6.0)
      vs. median 5.1 (95% CI 3.3-6.9), p < 0.01. The increased IPF shows a correlation
      with the PAS positivity [r(S) = 0.5 (p = 0.14) and r(S) = 0.6 (p = 0.05)] which
      has a tendency to increase [Group 2: median PAS 24.3% (95% CI 14.8-26.2) vs.
      median PAS 30% (95% CI 21.6-34.2), p = 0.05 and Group 3: median PAS 31% (95% CI
      19-36.4) vs. median PAS 27.4% (95% CI 18.7-34.9), p = 0.35] and correlated
      negatively with the decrease in the platelet count [Group 2: r(S) = -0.7 (p =
      0.21) and Group 3: r(S) = -0.5 (p = 0.14)]. Our findings support the significance
      of platelet evaluation by light microscopy to understand why morphologic changes
      of thrombocytopoiesis may be expected in thrombocytopenia due to donation of
      platelets.

PMID- 21736422
TI  - Succinate reverses in-vitro platelet inhibition by acetylsalicylic acid and P2Y
      receptor antagonists.
AB  - High on-treatment platelet reactivity has been associated with adverse
      cardiovascular events in patients receiving anti-platelet agents, but the
      molecular mechanisms underlying this phenomenon remain incompletely understood.
      Succinate, a citric acid cycle intermediate, is released into the circulation
      under conditions of mitochondrial dysfunction due to hypoxic organ damage,
      including sepsis, stroke, and myocardial infarction. Because the G protein
      coupled receptor (GPCR) for succinate, SUCNR1 (GPR91), is present on human
      platelets, we hypothesized that succinate-mediated platelet stimulation may
      counteract the pharmacological effects of cyclooxygenase-1 and ADP receptor
      antagonists. To test this hypothesis in a controlled in-vitro study, washed
      platelets from healthy donors were treated with acetylsalicylic acid (ASA) or
      small-molecule P2Y(1) or P2Y(12) inhibitors and subsequently analyzed by light
      transmittance aggregometry using arachidonic acid (AA), ADP and succinate as
      platelet agonists. Aggregation in response to succinate alone was highly variable
      with only 29% of donors showing a (mostly delayed) platelet response. In
      contrast, succinate reproducibly and concentration-dependently (10-1000 uM)
      enhanced platelet aggregation in response to low concentrations of exogenous ADP.
      Furthermore, while succinate alone had no effect in the presence of platelet
      inhibitors, responsiveness of platelets to ADP after pretreatment with P2Y(1) or
      P2Y(12) antagonists was fully restored, when platelets were co-stimulated with
      100 uM succinate. Similarly, succinate completely (at 1000 uM) or partially (at
      100 uM) reversed the inhibitory effect of ASA on AA-induced platelet aggregation.
      In contrast, succinate failed to restore platelet responsiveness in the presence
      of both ASA and the P2Y(12) antagonist, suggesting that concomitant signaling via
      different GPCRs was required. Essentially identical results were obtained, when
      flow cytometric analysis of surface CD62P expression was used as a different
      readout for platelet activation. In summary, extracellular succinate may have a
      co-stimulatory role in platelet aggregation and, by (partially) antagonizing the
      effects of platelet inhibitors, may contribute to the inter-individual
      variability frequently observed in platelet function testing.

PMID- 21736424
TI  - Enhancement of Gag-specific but reduction of Env- and Pol-specific CD8+ T cell
      responses by simian immunodeficiency virus nonstructural proteins in mice.
AB  - Accessory and regulatory proteins (nonstructural proteins) have received
      increasing attention as components in novel HIV/SIV vaccine design. However, the
      complicated interactions between nonstructural proteins and structural proteins
      remain poorly understood, especially their effects on immunogenicity. In this
      study, the immunogenicity of structural proteins in the presence and absence of
      nonstructural proteins was compared. First, a series of recombinant plasmids and
      adenoviral vectors carrying various SIVmac239 nonstructural and structural genes
      was constructed. Then mice were primed with DNA plasmids and boosted with
      corresponding Ad5 vectors of different combinations, and the resulting immune
      responses were measured. Our results demonstrated that when the individual Gag,
      Pol, or Env gene products were coimmunized with the whole repertoire of
      nonstructural proteins, the Gag-specific CD8(+) T response was greatly enhanced,
      while the Env- and Pol-specific CD8(+) T responses were significantly reduced.
      The same pattern was not observed in CD4(+) T cell responses. Antibody responses
      against both the Gag and Env proteins were elicited more effectively when these
      structural antigens were immunized together with nonstructural antigens. These
      findings may provide helpful insights into the development of novel HIV/SIV
      vaccines.

PMID- 21736423
TI  - Azithromycin plus chloroquine: combination therapy for protection against malaria
      and sexually transmitted infections in pregnancy.
AB  - INTRODUCTION: The first-line therapy for the intermittent preventive treatment of
      malaria in pregnancy (IPTp) is sulphadoxine-pyrimethamine (SP). There is an
      urgent need to identify safe, well-tolerated and efficacious alternatives to SP
      due to widespread Plasmodium falciparum resistance. Combination therapy using
      azithromycin and chloroquine is one possibility that has demonstrated adequate
      parasitological response > 95% in clinical trials of non-pregnant adults in sub
      Saharan Africa and where IPTp is a government policy in 33 countries. AREAS
      COVERED: Key safety, tolerability and efficacy data are presented for
      azithromycin and chloroquine, alone and/or in combination, when used to prevent
      and/or treat P. falciparum, P. vivax, and several curable sexually transmitted
      and reproductive tract infections (STI/RTI). Pharmacokinetic evidence from
      pregnant women is also summarized for both compounds. EXPERT OPINION: The
      azithromycin-chloroquine regimen that has demonstrated consistent efficacy in non
      pregnant adults has been a 3-day course containing daily doses of 1 g of
      azithromycin and 600 mg base of chloroquine. The pharmacokinetic evidence of
      these compounds individually suggests that dose adjustments may not be necessary
      when used in combination for treatment efficacy against P. falciparum, P. vivax,
      as well as several curable STI/RTI among pregnant women, although clinical
      confirmation will be necessary. Mass trachoma-treatment campaigns have shown that
      azithromycin selects for macrolide resistance in the pneumococcus, which reverses
      following the completion of therapy. Most importantly, no evidence to date
      suggests that azithromycin induces pneumococcal resistance to penicillin.

PMID- 21736425
TI  - The maturity of tissue-engineered cartilage in vitro affects the repairability
      for osteochondral defect.
AB  - Cartilage tissue engineering using cells and biocompatible scaffolds has emerged
      as a promising approach to repair of cartilage damage. To date, however, no
      engineered cartilage has proven to be equivalent to native cartilage in terms of
      biochemical and compression properties, as well as histological features. An
      alternative strategy for cartilage engineering is to focus on the in vivo
      regeneration potential of immature engineered cartilage. Here, we used a rabbit
      model to evaluate the extent to which the maturity of engineered cartilage
      influenced the remodeling and integration of implanted extracellular matrix
      scaffolds containing allogenous chondrocytes. Full-thickness osteochondral
      defects were created in the trochlear groove of New Zealand white rabbits. Left
      knee defects were left untreated as a control (group 1), and right knee defects
      were implanted with tissue-engineered cartilage cultured in vitro for 2 days
      (group 2), 2 weeks (group 3), or 4 weeks (group 4). Histological, chemical, and
      compression assays of engineered cartilage in vitro showed that biochemical
      composition became more cartilagenous, and biomechanical property for compression
      gradually increased with culture time. In an in vivo study, gross imaging and
      histological observation at 1 and 3 months after implanting in vitro-cultured
      engineered cartilage showed that defects in groups 3 and 4 were repaired with
      hyaline cartilage-like tissue, whereas defects were only partially filled with
      fibrocartilage after 1 month in groups 1 and 2. At 3 months, group 4 showed
      striking features of hyaline cartilage tissue, with a mature matrix and a
      columnar arrangement of chondrocytes. Zonal distribution of type II collagen was
      most prominent, and the International Cartilage Repair Society score was also
      highest at this time. In addition, the subchondral bone was well ossified. In
      conclusion, in vivo engineered cartilage was remodeled when implanted; however,
      its extent to maturity varied with cultivation period. Our results showed that
      the more matured the engineered cartilage was, the better repaired the
      osteochondral defect was, highlighting the importance of the in vitro cultivation
      period.

PMID- 21736426
TI  - Cell and tissue interactions of Treponema pallidum in primary and secondary
      syphilitic skin lesions: an ultrastructural study of serial sections.
AB  - There are limited reports on the ultrastructure of syphilis skin lesions. The aim
      of this study has been to perform an electron microscopic investigation of the
      morphology and the tissue distribution of treponemes in primary and secondary
      cutaneous lesions. Three cases of primary syphilitic chancre and one case of
      secondary syphilis were included. Prominent epidermal abnormalities in the
      primary chancre and a perivascular inflammatory infiltrate in the secondary
      lesion were found by light microscopy. Ultrastructurally, spirochetes were
      located mainly in the blood vessel walls and dermal tissue of the chancre
      lesions. In the secondary syphilis case, spirochetes were more abundant between
      epidermal keratinocytes. Most of them adjusted to the intercellular spaces.
      Occasionally, the electron microscopy images were highly suggestive of an
      intracellular location. Both the ultrastructural and immunohistochemical
      examination of the primary and secondary syphilis lesions showed a paradoxical
      distribution of the causative microorganisms compared to the light microscopic
      changes. In addition, the ultrastructural findings strongly suggest that
      Treponema pallidum subspecies pallidum invades tissues, not only through an
      intercellular, but also through a transcellular pathway.

PMID- 21736427
TI  - Who got vaccinated against H1N1 pandemic influenza? A longitudinal study in four
      U.S. cities.
AB  - The recent H1N1 pandemic influenza stimulated numerous studies into the attitudes
      and intentions about the H1N1 vaccine. However, no study has investigated
      prospective predictors of vaccination behaviour. We conducted a two-wave
      longitudinal study among residents in four U.S. cities during the course of the
      H1N1 outbreak, using Internet surveys to assess demographic, cognitive and
      emotional predictors of H1N1 vaccination behaviour. Surveys were conducted at two
      time points, before (Time 1) and after (Time 2) the H1N1 vaccine was widely
      available to the public. Results show that Time 2 vaccination rates, but not Time
      1 vaccination intentions, tracked H1N1 prevalence across the four cities. Receipt
      of seasonal influenza vaccine in the previous year, worry, compliance with
      recommended interventions, household size and education assessed at Time 1 were
      significant prospective predictors of vaccination behaviour. Perception of the
      H1N1 vaccine, social influence and prioritised vaccine recipient status assessed
      at Time 2 also predicted vaccination behaviour. Critically, worry about H1N1
      mediated the effects of both objective risk (prevalence at the city level) and
      perceived risk on vaccination behaviour. These results suggest that H1N1
      vaccination behaviour appropriately reflected objective risk across regions, and
      worry acted as the mechanism by which vaccination behaviour followed objective
      risk.

PMID- 21736428
TI  - Ab initio predictions of structural and elastic properties of struvite:
      contribution to urinary stone research.
AB  - In the present work, we carried out density functional calculations of struvite-
      the main component of the so-called infectious urinary stones--to study its
      structural and elastic properties. Using a local density approximation and a
      generalised gradient approximation, we calculated the equilibrium structural
      parameters and elastic constants C(ijkl). At present, there is no experimental
      data for these elastic constants C (ijkl) for comparison. Besides the elastic
      constants, we also present the calculated macroscopic mechanical parameters,
      namely the bulk modulus (K), the shear modulus (G) and Young's modulus (E). The
      values of these moduli are found to be in good agreement with available
      experimental data. Our results imply that the mechanical stability of struvite is
      limited by the shear modulus, G. The study also explores the energy-band
      structure to understand the obtained values of the elastic constants.

PMID- 21736429
TI  - Automated measurement of neural foramen cross-sectional area during in vivo
      functional movement.
AB  - An automated technique to measure neural foramen cross-sectional area during in
      vivo, multi-planar movements is presented. This method combines three-dimensional
      (3D) models of each vertebra obtained from CT scans with in vivo movement data
      collected using high-speed biplane radiography. A novel computer algorithm that
      automatically traces a path around the bony boundary that defines the neural
      foramen at every frame of X-ray data is described. After identifying the neural
      foramen boundary, the cross-sectional area is calculated. The technique is
      demonstrated using data collected from a patient with cervical radiculopathy who
      is tested before and after conservative treatment. The technique presented here
      can be applied when 3D, dynamic, functional movements are performed. Neural
      foramen cross-sectional area can be quantified at specific angles of
      intervertebral rotation, allowing for matched comparisons between two trials or
      two test sessions. The present technique is ideal for longitudinal studies
      involving subjects who receive conservative or surgical treatments that may
      affect spine motion.

PMID- 21736430
TI  - The tasks of self-managing hepatitis C: the significance of disclosure.
AB  - The narratives of those with hepatitis C were viewed through the lens of Corbin
      and Strauss' [Corbin, J., & Strauss, A. (1988). Unending work and care: Managing
      chronic illness at home. The Jossey-Bass health series and The Jossey-Bass social
      and behavioral science series. San Francisco, CA: Jossey-Bass.] self-management
      model for chronic illness, using qualitative methodology. Fifteen Australian
      hepatitis C positive interviewees described the challenges and turning points in
      adjusting to their diagnosis. The data were analysed using open- and closed
      coding methods. Support was found for a self-management model encompassing
      medical, emotional and life role facets for those adjusting to life with
      hepatitis C. Unique challenges emerged beyond those described by Corbin and
      Strauss (1988), namely that disclosure impacted both positively and negatively on
      the tasks of self-management. It was concluded that self-management may be
      compromised by disclosure, particularly distress derived from hepatitis C-related
      stigma. The self-management tasks described contribute to broadening clinicians'
      understanding of the challenges faced by those living with hepatitis C.

PMID- 21736431
TI  - Illness representations and distress in women undergoing screening for familial
      ovarian cancer.
AB  - Women with a familial or genetic predisposition to ovarian cancer are at
      significantly increased risk of developing the disease, and this warrants
      effective risk management strategies. A clinical trial of ovarian cancer
      screening (OCS) is being conducted to establish the effectiveness of this risk
      management strategy. This article reports data from its psychological partner
      study which aims to evaluate the psychological effects of OCS. Leventhal's Self
      Regulatory Model provided the theoretical framework for understanding emotional
      responses to OCS. The revised Illness Perceptions Questionnaire (IPQ-R) is based
      on this model and the IPQ-R, adapted to the risk of ovarian cancer, was completed
      by women (N = 1999) prior to screening. The original IPQ-R factor structure was
      not replicated but IPQ-R variables explained 14.70% of the variance in women's
      ovarian cancer-specific distress after controlling for age, general anxiety and
      depression. Negative emotional representations of ovarian cancer risk and general
      anxiety were moderately associated with greater ovarian cancer-specific distress
      whereas cognitive illness representations were weakly related to ovarian cancer
      specific distress. Further analyses of data from the ongoing psychological
      evaluation are needed to determine the predictive utility of IPQ-R variables in
      explaining distress during OCS.

PMID- 21736432
TI  - For love or money? What motivates people to know the minds of others?
AB  - Mood affects social cognition and "theory of mind", such that people in a
      persistent negative mood (i.e., dysphoria) have enhanced abilities at making
      subtle judgements about others' mental states. Theorists have argued that this
      hypersensitivity to subtle social cues may have adaptive significance in terms of
      solving interpersonal problems and/or minimising social risk. We tested whether
      increasing the social salience of a theory of mind task would preferentially
      increase dyspshoric individuals' performance on the task. Forty-four dysphoric
      and 51 non-dysphoric undergraduate women participated in a theory of mind
      decoding task following one of three motivational manipulations: (i) social
      motivation (ii) monetary motivation, or (iii) no motivation. Social motivation
      was associated with the greatest accuracy of mental state decoding for the
      dysphoric group, whereas the non-dysphoric group showed the highest accuracy in
      the monetary motivation condition. These results suggest that dysphoric
      individuals may be especially, and preferentially, motivated to understand the
      mental states of others.

PMID- 21736433
TI  - Exploring the relationship between retrieval disruption from collaboration and
      recall.
AB  - When people recall together in a collaborative group they recall less than their
      potential. This phenomenon of collaborative inhibition is explained in terms of
      retrieval disruption. However, collaborative recall also re-exposes individuals
      to items recalled by others that they themselves might otherwise have forgotten.
      This re-exposure produces post-collaborative benefits in individual recall. The
      current study examined whether reduced retrieval disruption during group recall
      is related not only to less collaborative inhibition, but also to greater post
      collaborative recall benefits. To test this we devised a paradigm to calculate
      the extent to which each individual experienced retrieval disruption during group
      recall. We also included two types of collaborative groups, one of which was
      expected to experience greater retrieval disruption than the other. Results
      suggest that the relationship between retrieval disruption and recall performance
      depends on the level at which retrieval disruption is measured. When retrieval
      disruption was assessed at the individual level, then minimising retrieval
      disruption was associated with higher recall (i.e., less collaborative inhibition
      and greater post-collaborative individual recall). However, when retrieval
      disruption was assessed at the group level there was no relationship with recall.
      Furthermore, the findings from this design suggest a role of cross-cueing in
      modulating group recall levels.

PMID- 21736434
TI  - Age effects shrink when motor learning is predominantly supported by
      nondeclarative, automatic memory processes: evidence from golf putting.
AB  - Can motor learning be equivalent in younger and older adults? To address this
      question, 48 younger (M = 23.5 years) and 48 older (M = 65.0 years) participants
      learned to perform a golf-putting task in two different motor learning
      situations: one that resulted in infrequent errors or one that resulted in
      frequent errors. The results demonstrated that infrequent-error learning
      predominantly relied on nondeclarative, automatic memory processes whereas
      frequent-error learning predominantly relied on declarative, effortful memory
      processes: After learning, infrequent-error learners verbalized fewer strategies
      than frequent-error learners; at transfer, a concurrent, attention-demanding
      secondary task (tone counting) left motor performance of infrequent-error
      learners unaffected but impaired that of frequent-error learners. The results
      showed age-equivalent motor performance in infrequent-error learning but age
      deficits in frequent-error learning. Motor performance of frequent-error learners
      required more attention with age, as evidenced by an age deficit on the attention
      demanding secondary task. The disappearance of age effects when nondeclarative,
      automatic memory processes predominated suggests that these processes are
      preserved with age and are available even early in motor learning.

PMID- 21736435
TI  - Assessing the validity of multinomial models using extraneous variables: an
      application to prospective memory.
AB  - The class of multinomial processing tree (MPT) models has been used extensively
      in cognitive psychology to model latent cognitive processes. Critical for the
      usefulness of a MPT model is its psychological validity. Generally, the validity
      of a MPT model is demonstrated by showing that its parameters are selectively and
      predictably affected by theoretically meaningful experimental manipulations.
      Another approach is to test the convergent validity of the model parameters and
      other extraneous measures intended to measure the same cognitive processes. Here,
      we advance the concept of construct validity (Cronbach & Meehl,  1955 ) as a
      criterion for model validity in MPT modelling and show how this approach can be
      fruitfully utilized using the example of a MPT model of event-based prospective
      memory. For that purpose, we investigated the convergent validity of the model
      parameters and established extraneous measures of prospective memory processes
      over a range of experimental settings, and we found a lack of convergent validity
      between the two indices. On a conceptual level, these results illustrate the
      importance of testing convergent validity. Additionally, they have implications
      for prospective memory research, because they demonstrate that the MPT model of
      event-based prospective memory is not able to differentiate between different
      processes contributing to prospective memory performance.

PMID- 21736436
TI  - The influence of sentential position on noun phrase structure priming.
AB  - This article explores the interaction between global sentence context and local
      syntactic decision making. Specifically, four noun phrase (NP) structural priming
      experiments investigated whether the position of an NP within a sentence
      increased speakers' tendency to repeat primed structure. We crossed the position
      of the NP with the structure of the NP, such that NPs could be sentence initial
      or final in prime sentences. We further manipulated whether the to-be-modified
      target NP was sentence initial or final. Structural persistence effects were
      consistently observed, but there was no influence of parallel position. Rather,
      sentence-initial NP primes had a stronger influence on subsequent syntactic
      decisions than sentence-final primes, suggesting a primacy effect. Sentence
      initial target NPs contributed to this primacy effect, while sentence-final
      target NPs did not. We argue that this primacy effect arises as the result of
      greater processing demands and resources for early than for late sentence
      constituents as well as deeper encoding and more focused attention when
      processing the beginnings of sentences.

PMID- 21736437
TI  - Two new 3-oxo-alpha-ionol glucosides from Urtica laetevirens Maxim.
AB  - Two new 3-oxo-alpha-ionol glucoside isomers, (6R,9R)-3-oxo-alpha-ionol-9-O-beta-D
      glucopyranosyl (1 -> 2)-beta-D-glucopyranoside (1) and (6S,9R)-3-oxo-alpha-ionol
      9-O-beta-D-glucopyranosyl (1 -> 2)-beta-D-glucopyranoside (2) were isolated from
      the aerial parts of Urtica laetevirens Maxim. Their structures, including
      stereochemistry, were established by spectral analyses (HR-ESI-MS, NMR and CD).
      Also, 3-oxo-alpha-ionol glucosides were isolated from Urtica species for the
      first time.

PMID- 21736438
TI  - Investigation of the acceptance of a handbook for safe driving at an older age.
AB  - The objective of this research is the investigation of older drivers' attitudes
      towards a handbook for safe driving at an older age. The handbook was developed
      with the purpose of increasing elderly drivers' awareness of their driving
      abilities and providing information about the effects of ageing on driving and
      about safe driving practices and compensation strategies. A survey was carried
      out in which 64 active drivers between 65 and 74 years of age participated.
      Participants regard the handbook for safe driving as useful, interesting,
      providing knowledge and relevant information. More than half of them reported
      that they had become more aware of changes in their driving after reading it.
      Binary logistic analysis was conducted to identify individual driver
      characteristics that might predict acceptance of the handbook by active older
      drivers in terms of reported increased awareness and intended repeated use. The
      findings of the research indicate a positive attitude of elderly active drivers
      towards the handbook, implying acceptance by its users. The characteristics of
      the drivers' who reported increased awareness after reading have been identified.

PMID- 21736439
TI  - The Hellenic and Hippocratic origins of the spinal terminology.
AB  - Numerous Hellenic terms have been gradually adopted during the development of
      modern medical science. Moreover, there are a significant number of words that
      derive directly from the Hippocratic texts. Hippocrates (ca. 460-ca. 377 BC),
      revered as the father of medicine, and his followers left behind a valuable
      heritage of medical knowledge that, practically, laid the foundations of Western
      medicine. Their theories, collected in Corpus Hippocraticum, transformed medicine
      by adding, mainly, clinical observation and inductive reasoning as significant
      parts of medical diagnosis and treatment. Additionally, Hippocratic writings have
      provided an invaluable heritage of medical terms for all medical fields. The
      present article examines the Hellenic and Hippocratic terminology referring to
      the spine and how this vocabulary has influenced and dominated upon modern spinal
      onomatology.

PMID- 21736441
TI  - Discovering the African freshwater "torpedo": legendary Ethiopia, religious
      controversies, and a catfish capable of reanimating dead fish.
AB  - The electric catfishes of African rivers and lakes, once depicted on Egyptian
      tomb art, have been largely overlooked in histories and reviews of electric fish
      biology and animal electricity. This article examines how Westerners, especially
      Dominican and Jesuit missionaries, discovered them in Ethiopia and other parts of
      Africa at the beginning of the seventeenth century. What transpired took place
      against the backdrop of tales involving the Bible, Prester John's mythical
      empire, and imaginary animals with fabulous powers. In effect, how they were
      found is related to attempts to convert Ethiopian Christians to true Catholicism,
      hopes of discovering great riches, and opportunities to trade, and not with the
      efforts of skilled natural philosophers to document and conduct experiments on
      the wildlife of this continent. Nevertheless, the early descriptions by Europeans
      circulated, and during the next century these catfishes began to be used in
      experiments that helped to make animal electricity a reality.

PMID- 21736442
TI  - Brain heraldic tinctures and evolution theory: a sensational turn of events that
      should have been kept secret.

PMID- 21736445
TI  - An integrated geometric modelling framework for patient-specific computational
      haemodynamic study on wide-ranged vascular network.
AB  - Patient-specific haemodynamic computations have been used as an effective tool in
      researches on cardiovascular disease associated with haemodynamics such as
      atherosclerosis and aneurysm. Recent development of computer resource has enabled
      3D haemodynamic computations in wide-spread arterial network but there are still
      difficulties in modelling vascular geometry because of noise and limited
      resolution in medical images. In this paper, an integrated framework to model an
      arterial network tree for patient-specific computational haemodynamic study is
      developed. With this framework, 3D vascular geometry reconstruction of an
      arterial network and quantification of its geometric feature are aimed. The
      combination of 3D haemodynamic computation and vascular morphology quantification
      helps better understand the relationship between vascular morphology and
      haemodynamic force behind 'geometric risk factor' for cardiovascular diseases.
      The proposed method is applied to an intracranial arterial network to demonstrate
      its accuracy and effectiveness. The results are compared with the marching-cubes
      (MC) method. The comparison shows that the present modelling method can
      reconstruct a wide-ranged vascular network anatomically more accurate than the MC
      method, particularly in peripheral circulation where the image resolution is low
      in comparison to the vessel diameter, because of the recognition of an arterial
      network connectivity based on its centreline.

PMID- 21736446
TI  - Silk-fibrin/hyaluronic acid composite gels for nucleus pulposus tissue
      regeneration.
AB  - Scaffold designs are critical for in vitro culture of tissue-engineered cartilage
      in three-dimensional environments to enhance cellular differentiation for tissue
      engineering and regenerative medicine. In the present study we demonstrated silk
      and fibrin/hyaluronic acid (HA) composite gels as scaffolds for nucleus pulposus
      (NP) cartilage formation, providing both biochemical support for NP outcomes as
      well as fostering the retention of size of the scaffold during culture due to the
      combined features of the two proteins. Passage two (P2) human chondrocytes
      cultured in 10% serum were encapsulated within silk-fibrin/HA gels. Five study
      groups with fibrin/HA gel culture (F/H) along with varying silk concentrations
      (2% silk gel only, fibrin/HA gel culture with 1% silk [F/H+1S], 1.5% silk
      [F/H+1.5S], and 2% silk [F/H+2S]) were cultured in serum-free chondrogenic
      defined media (CDM) for 4 weeks. Histological examination with alcian blue showed
      a defined chondrogenic area at 1 week in all groups that widened homogenously
      until 4 weeks. In particular, chondrogenic differentiation observed in the
      F/H+1.5S had no reduction in size throughout the culture period. The results of
      biochemical and molecular biological evaluations supported observations made
      during histological examination. Mechanical strength measurements showed that the
      silk mixed gels provided stronger mechanical properties for NP tissue than
      fibrin/HA composite gels in CDM. This effect could potentially be useful in the
      study of in vitro NP tissue engineering as well as for clinical implications for
      NP tissue regeneration.

PMID- 21736447
TI  - The satisfaction of Latina breast cancer survivors with their healthcare and
      health-related quality of life.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship of satisfaction
      with the cancer care doctor and health-related quality of life (HRQOL) among
      Latina breast cancer survivors (BCS) by (1) assessing whether satisfaction would
      be positively correlated with HRQOL and (2) assessing whether satisfaction would
      significantly influence HRQOL while controlling for covariates. METHODS: The
      cross-sectional study used self-report data from 117 Latina BCS. Satisfaction was
      measured with the Hall Satisfaction Index, and HRQOL was measured with the
      Functional Assessment of Cancer Therapy-General (FACT-G). Analyses included
      calculation of descriptive statistics, t tests, bivariate correlations, analyses
      of variance (ANOVAs), and multivariate analyses. RESULTS: Latina BCS had high
      satisfaction and generally good HRQOL. The Hall Satisfaction Index total score
      was positively associated with FACT-G functional well-being (r=0.265, p=0.004).
      Multivariate analyses showed that the Hall Satisfaction Index total score was a
      significant predictor of FACT-G functional well-being (p=0.012). Employment
      status was also a significant predictor, where being employed or retired resulted
      in better functional well-being than being unemployed. CONCLUSIONS: Latina BCS
      were quite satisfied with their cancer care doctors, and high levels of
      satisfaction with the cancer care doctor influenced functional well-being when
      confounding variables were controlled. Despite reportedly high satisfaction,
      Latina BCS did report barriers to satisfaction that could be considered cultural.
      Implications are discussed.

PMID- 21736448
TI  - Administration of the same dose of epoetin-beta intravenously and subcutaneously
      to patients with renal anaemia.
AB  - OBJECTIVE: Subcutaneous (s.c.) administration of erythropoietin (EPO) is
      recommended over the intravenous (i.v.) route to reduce doses and costs. Optimal
      iron treatment is important for the optimal EPO effect. This study investigated
      whether the haemoglobin (Hb) level of a single patient could be preserved with
      the same dose of EPO given i.v. as given s.c. MATERIAL AND METHODS: One-hundred
      and forty-five haemodialysis patients with the same weekly EPO dose s.c. for 3
      months and a stable Hb (maximum fluctuation of 1 mmol/l) were randomized in a
      crossover study to group A (4 months i.v. then 4 months s.c. EPO) or group B (4
      months s.c. then 4 months i.v. EPO, with unchanged EPO dose). Ferritin had to be
      300-800 MUg/l or transferrin saturation >= 20%. Patients with a fall in Hb >1
      mmol/l were withdrawn. RESULTS: Ferritin and transferrin saturation remained
      within the target range, and mean Hb in the range of 1 mmol/l. Mean EPO doses
      were unchanged in both groups, and no difference was found between the dropouts
      due to Hb fall >1 mmol/l in the i.v. and s.c. groups during the first period of
      the trial. CONCLUSION: In iron-replete haemodialysis patients the same EPO dose
      given intravenously is just as effective as given subcutaneously.

PMID- 21736449
TI  - Age dependency of central and peripheral systolic blood pressures: cross
      sectional and longitudinal observations in European populations.
AB  - BACKGROUND: As arteries become stiffer with ageing, reflected waves move faster
      and augment late systolic pressure. We investigated the age dependency of
      peripheral and central systolic pressure, pressure amplification (peripheral
      systolic blood pressure - central systolic blood pressure), and peripheral and
      central systolic augmentation (maximal systolic pressure minus the first peak of
      the pressure wave). METHODS: We randomly recruited 1420 White Europeans (mean
      age, 41.7 years). peripheral systolic blood pressure and central systolic blood
      pressure were measured by means of an oscillometric sphygmomanometer and pulse
      wave analysis, respectively. RESULTS: In cross-sectional analyses (731 women, 689
      men), central systolic blood pressure and central systolic augmentation increased
      more with age than peripheral systolic blood pressure and peripheral systolic
      augmentation. These age-related increases were greater in women than men. The age
      related decrease in pressure amplification was similar in both sexes. In
      longitudinal analyses (208 women, 190 men), the annual increases in central
      systolic blood pressure and central systolic augmentation were steeper (p <
      0.001) than those in peripheral systolic blood pressure and peripheral systolic
      augmentation with no sex differences (p >= 0.068), except for peripheral systolic
      augmentation, which was larger in women (p = 0.002). Longitudinally, pressure
      amplification decreased more with age in women than men (p = 0.012). In
      multivariable-adjusted analyses, age was the overriding determinant of peripheral
      systolic blood pressure and central systolic blood pressure. CONCLUSION: With
      ageing, peripheral systolic blood pressure approximates to central systolic blood
      pressure. This might explain why in older subjects peripheral systolic blood
      pressure becomes the main predictor of cardiovascular complications.

PMID- 21736450
TI  - Reconstruction of three-dimensional neourethra using lingual keratinocytes and
      corporal smooth muscle cells seeded acellular corporal spongiosum.
AB  - Tissue engineering technique seems to be the best strategy for treating the
      urethra disease in the near future. In present study, porcine acellular corpus
      spongiosum matrices (ACSMs) were combined with autologus corporal smooth muscle
      cells (CSMCs) and lingual keratinocytes by static-dynamic seeding method to form
      three-dimensional (3D) "neourethra" tissue for repairing the urethral defection.
      Six scaffolds with two kinds of cells (Group C), six scaffolds with only lingual
      keratinocytes (Group B), and six matrices alone (Group A) were used to repair the
      rabbit urethral defection. Retrograde urethrography and histological analyses
      were performed to evaluate the results of urethroplasty. In vitro, hematoxylin
      and eosin staining of seeded ACSM showed multiple epithelial layers and well
      distributed CSMCs into the matrix. In vivo, the urethra kept a wide caliber in
      Group C. Strictures were observed in groups A and B. Histologically, the
      retrieved urethra in group A showed fibrosis and inflammation during 6 months.
      Simple epithelial layer regenerated in group B while there was no evidence of
      CSMCs growing into grafts during study period. Stratified epithelial layer and
      organized muscle fiber bundles were evident after 6 months in group C. Our study
      suggested that lingual keratinocytes and CSMCs could be used as a source of seed
      cells for urethral tissue engineering. Using the dynamic-static seeding method,
      3D urethra could be constructed in vivo.

PMID- 21736451
TI  - Similarity between brain activity at encoding and retrieval predicts successful
      realization of delayed intentions.
AB  - Remembering delayed intentions can be highly demanding. Accuracy in laboratory
      paradigms assessing prospective memory (PM) is typically well below ceiling, and
      failure to remember intended behaviors after a delay is a common occurrence in
      everyday life. However, relatively little is known of the potential differences
      in brain activity that distinguish successful versus unsuccessful PM. In this
      fMRI study, participants repeatedly encoded, stored, and then had the opportunity
      to retrieve intended behaviors while engaged in a distracting ongoing task. This
      yielded a success rate of approximately two thirds. Overall levels of brain
      activity distinguished successful versus unsuccessful trials at all three stages
      (encoding, storage, and retrieval), suggesting multiple neural determinants of PM
      success. In addition, the voxelwise similarity between patterns of brain activity
      at encoding and retrieval was greater for successful than unsuccessful trials.
      This was true even in posterior cingulate, which showed opposite patterns of
      signal change between encoding and retrieval. Thus, successful realization of
      delayed intentions may be associated with reinstatement of encoding context at
      the time of retrieval.

PMID- 21736452
TI  - Opposite effects of cortisol on consolidation of temporal sequence memory during
      waking and sleep.
AB  - Memory functions involve three stages: encoding, consolidation, and retrieval.
      Modulating effects of glucocorticoids (GCs) have been consistently observed for
      declarative memory with GCs enhancing encoding and impairing retrieval, but
      surprisingly, little is known on how GCs affect memory consolidation. Studies in
      rats suggest a beneficial effect of GCs that were administered during
      postlearning wake periods, whereas in humans, cortisol impaired memory
      consolidation when administered during postlearning sleep. These inconsistent
      results raise the question whether effects of GCs critically depend on the brain
      state during consolidation (sleep vs. wake). Here, we compare for the first time
      directly the effects of cortisol on memory consolidation during postlearning
      sleep and wakefulness in different measures of declarative memory. Cortisol (13
      mg vs. placebo) was intravenously infused during a postlearning nap or a time
      matched period of wakefulness after participants had encoded neutral and
      emotional text material. Memory for the texts was tested (a) by asking for the
      contents of the texts ("item" memory) and (b) for the temporal order of the
      contents within the texts ("relational" memory). Neither postlearning infusion of
      cortisol during sleep nor during wakefulness affected retention of content words
      of emotional or neutral texts. Critically, however, the retention of temporal
      order within the texts, known to rely most specifically on the hippocampus proper
      within the medial-temporal lobe memory system, was distinctly improved by
      cortisol infusion during the wake phase but impaired by cortisol during sleep.
      These results point toward fundamentally different mechanisms of hippocampal
      memory consolidation, depending on the brain state.

PMID- 21736453
TI  - Pre-experimental familiarization increases hippocampal activity for both targets
      and lures in recognition memory: an fMRI study.
AB  - In the present study, items pre-exposed in a familiarization series were included
      in a list discrimination task to manipulate memory strength. At test,
      participants were required to discriminate strong targets and strong lures from
      weak targets and new lures. This resulted in a concordant pattern of increased
      "old" responses to strong targets and lures. Model estimates attributed this
      pattern to either equivalent increases in memory strength across the two types of
      items (unequal variance signal detection model) or equivalent increases in both
      familiarity and recollection (dual process signal detection [DPSD] model).
      Hippocampal activity associated with strong targets and lures showed equivalent
      increases compared with missed items. This remained the case when analyses were
      restricted to high-confidence responses considered by the DPSD model to reflect
      predominantly recollection. A similar pattern of activity was observed in
      parahippocampal cortex for high-confidence responses. The present results are
      incompatible with "noncriterial" or "false" recollection being reflected solely
      in inflated DPSD familiarity estimates and support a positive correlation between
      hippocampal activity and memory strength irrespective of the accuracy of list
      discrimination, consistent with the unequal variance signal detection model
      account.

PMID- 21736454
TI  - Neural correlates of confidence during item recognition and source memory
      retrieval: evidence for both dual-process and strength memory theories.
AB  - Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered
      primary nodes in the episodic memory network, there is much debate regarding the
      contributions of MTL, PFC, and parietal subregions to recollection versus
      familiarity (dual-process theory) and the feasibility of accounts on the basis of
      a single memory strength process (strength theory). To investigate these issues,
      the current fMRI study measured activity during retrieval of memories that
      differed quantitatively in terms of strength (high vs. low-confidence trials) and
      qualitatively in terms of recollection versus familiarity (source vs. item memory
      tasks). Support for each theory varied depending on which node of the episodic
      memory network was considered. Results from MTL best fit a dual-process account,
      as a dissociation was found between a right hippocampal region showing high
      confidence activity during the source memory task and bilateral rhinal regions
      showing high-confidence activity during the item memory task. Within PFC, several
      left-lateralized regions showed greater activity for source than item memory,
      consistent with recollective orienting, whereas a right-lateralized ventrolateral
      area showed low-confidence activity in both tasks, consistent with monitoring
      processes. Parietal findings were generally consistent with strength theory, with
      dorsal areas showing low-confidence activity and ventral areas showing high
      confidence activity in both tasks. This dissociation fits with an attentional
      account of parietal functions during episodic retrieval. The results suggest that
      both dual-process and strength theories are partly correct, highlighting the need
      for an integrated model that links to more general cognitive theories to account
      for observed neural activity during episodic memory retrieval.

PMID- 21736455
TI  - Neural dissociation of number from letter recognition and its relationship to
      parietal numerical processing.
AB  - The visual recognition of letters dissociates from the recognition of numbers at
      both the behavioral and neural level. In this article, using fMRI, we investigate
      whether the visual recognition of numbers dissociates from letters, thereby
      establishing a double dissociation. In Experiment 1, participants viewed strings
      of consonants and Arabic numerals. We found that letters activated the left
      midfusiform and inferior temporal gyri more than numbers, replicating previous
      studies, whereas numbers activated a right lateral occipital area more than
      letters at the group level. Because the distinction between letters and numbers
      is culturally defined and relatively arbitrary, this double dissociation provides
      some of the strongest evidence to date that a neural dissociation can emerge as a
      result of experience. We then investigated a potential source of the observed
      neural dissociation. Specifically, we tested the hypothesis that lateralization
      of visual number recognition depends on lateralization of higher-order numerical
      processing. In Experiment 2, the same participants performed addition,
      subtraction, and counting on arrays of nonsymbolic stimuli varying in numerosity,
      which produced neural activity in and around the intraparietal sulcus, a region
      associated with higher-order numerical processing. We found that individual
      differences in the lateralization of number activity in visual cortex could be
      explained by individual differences in the lateralization of numerical processing
      in parietal cortex, suggesting a functional relationship between the two regions.
      Together, these results demonstrate a neural double dissociation between letter
      and number recognition and suggest that higher-level numerical processing in
      parietal cortex may influence the neural organization of number processing in
      visual cortex.

PMID- 21736456
TI  - Enhanced passive and active processing of syllables in musician children.
AB  - The aim of this study was to examine the influence of musical expertise in 9-year
      old children on passive (as reflected by MMN) and active (as reflected by
      discrimination accuracy) processing of speech sounds. Musician and nonmusician
      children were presented with a sequence of syllables that included standards and
      deviants in vowel frequency, vowel duration, and VOT. Both the passive and the
      active processing of duration and VOT deviants were enhanced in musician compared
      with nonmusician children. Moreover, although no effect was found on the passive
      processing of frequency, active frequency discrimination was enhanced in musician
      children. These findings are discussed in terms of common processing of acoustic
      features in music and speech and of positive transfer of training from music to
      the more abstract phonological representations of speech units (syllables).

PMID- 21736457
TI  - Attention modulates maintenance of representations in visual short-term memory.
AB  - Recent studies have shown that selective attention is of considerable importance
      for encoding task-relevant items into visual short-term memory (VSTM) according
      to our behavioral goals. However, it is not known whether top-down attentional
      biases can continue to operate during the maintenance period of VSTM. We used
      ERPs to investigate this question across two experiments. Specifically, we tested
      whether orienting attention to a given spatial location within a VSTM
      representation resulted in modulation of the contralateral delay activity (CDA),
      a lateralized ERP marker of VSTM maintenance generated when participants
      selectively encode memory items from one hemifield. In both experiments,
      retrospective cues during the maintenance period could predict a specific item
      (spatial retrocue) or multiple items (neutral retrocue) that would be probed at
      the end of the memory delay. Our results revealed that VSTM performance is
      significantly improved by orienting attention to the location of a task-relevant
      item. The behavioral benefit was accompanied by modulation of neural activity
      involved in VSTM maintenance. Spatial retrocues reduced the magnitude of the CDA,
      consistent with a reduction in memory load. Our results provide direct evidence
      that top-down control modulates neural activity associated with maintenance in
      VSTM, biasing competition in favor of the task-relevant information.

PMID- 21736458
TI  - Observing degradation of visual representations over short intervals when medial
      temporal lobe is damaged.
AB  - Medial temporal lobe (MTL) contributions to the brief maintenance of visual
      representations were evaluated by studying a group of patients with MTL damage.
      Eye movements of patients and healthy comparison subjects were tracked while
      performing a visual search for a target among complex stimuli of varying
      similarity to that target. Despite the task having no imposed delays, patients
      were impaired behaviorally, and eye movement measures showed abnormally rapid
      degradation of target representations in the patients. Eye movement data showed a
      modulation of the duration of fixations as a function of the similarity of
      fixated array lures to the target, but the effect was attenuated in patients
      during long fixation paths away from the sample target. This effect manifested
      despite patients' shorter searches and more frequent fixations of the sample
      target. Novel techniques provided unique insight into visual representation
      without healthy MTL, which may support maintenance of information through
      hippocampal-dependent relational binding.

PMID- 21736459
TI  - Vigor in the face of fluctuating rates of reward: an experimental examination.
AB  - Two fundamental questions underlie the expression of behavior, namely what to do
      and how vigorously to do it. The former is the topic of an overwhelming wealth of
      theoretical and empirical work particularly in the fields of reinforcement
      learning and decision-making, with various forms of affective prediction error
      playing key roles. Although vigor concerns motivation, and so is the subject of
      many empirical studies in diverse fields, it has suffered a dearth of
      computational models. Recently, Niv et al. [Niv, Y., Daw, N. D., Joel, D., &
      Dayan, P. Tonic dopamine: Opportunity costs and the control of response vigor.
      Psychopharmacology (Berlin), 191, 507-520, 2007] suggested that vigor should be
      controlled by the opportunity cost of time, which is itself determined by the
      average rate of reward. This coupling of reward rate and vigor can be shown to be
      optimal under the theory of average return reinforcement learning for a
      particular class of tasks but may also be a more general, perhaps hard-wired,
      characteristic of the architecture of control. We, therefore, tested the
      hypothesis that healthy human participants would adjust their RTs on the basis of
      the average rate of reward. We measured RTs in an odd-ball discrimination task
      for rewards whose magnitudes varied slowly but systematically. Linear regression
      on the subjects' individual RTs using the time varying average rate of reward as
      the regressor of interest, and including nuisance regressors such as the
      immediate reward in a round and in the preceding round, showed that a significant
      fraction of the variance in subjects' RTs could indeed be explained by the rate
      of experienced reward. This validates one of the key proposals associated with
      the model, illuminating an apparently mandatory form of coupling that may involve
      tonic levels of dopamine.

PMID- 21736460
TI  - Division of labor between lateral and ventral extrastriate representations of
      faces, bodies, and objects.
AB  - The occipito-temporal cortex is strongly implicated in carrying out the high
      level computations associated with vision. In human neuroimaging studies, focal
      regions are consistently found within this broad region that respond strongly and
      selectively to faces, bodies, or objects. A notable feature of these selective
      regions is that they are found in pairs. In the posterior-lateral occipito
      temporal cortex, focal selectivity is found for faces (occipital face area),
      bodies (extrastriate body area), and objects (lateral occipital). These three
      areas are found bilaterally and at close quarters to each other. Likewise, in the
      ventro-medial occipito-temporal cortex, three similar category-selective regions
      are found, also in proximity to each other: for faces (fusiform face area),
      bodies (fusiform body area), and objects (posterior fusiform). Here we review
      some of the extensive evidence on the functional properties of these areas with
      two aims. First, we seek to identify principles that distinguish the posterior
      lateral and ventro-medial clusters of selective regions but that apply generally
      within each cluster across the three stimulus kinds. Our review identifies and
      elaborates several principles by which these relationships hold. In brief, the
      posterior-lateral representations are more primitive, local, and stimulus-driven
      relative to the ventro-medial representations, which in contrast are more
      invariant to visual features, global, and linked to the subjective percept.
      Second, because the evidence base of studies that compare both posterior-lateral
      and ventro-medial representations of faces, bodies, and objects is still
      relatively small, we seek to provoke more cross-talk among the research strands
      that are traditionally separate. We identify several promising approaches for
      such future work.

PMID- 21736461
TI  - Looking at ECT through different lenses.

PMID- 21736462
TI  - Being in a safe haven and struggling against alcohol dependency. The meaning of
      caring for male patients in advanced addiction nursing.
AB  - The aim of the present study was to explore and illuminate the meaning of
      advanced nursing caring for men with alcohol dependency, as narrated by the men
      themselves. Ten male patients were interviewed in-depth and data were subjected
      to a phenomenological-hermeneutic analysis. Caring meant having the opportunity
      to rest in a safe haven together with professional caregivers, to struggle for
      liberation from dependency, and to expand the life-sphere by starting to accept
      oneself and broaden social participation. The findings illuminate various
      patterns of masculinity and point to the importance for caregivers to be open to
      challenging stereotypical gender assumptions.

PMID- 21736463
TI  - Educating for wellness: a wellness education group intervention for adults with
      chronic severe mental illness living in the community.
AB  - Chronic severe mental illness (CSMI) is a common disorder in the United States
      associated with numerous adverse health effects. Health promotion educational
      interventions can be beneficial. The purpose of this project was to implement and
      evaluate a community-based educational program for adults with CSMI. Analyses of
      quantitative and qualitative data showed overall satisfaction with the program
      and achievement of some specific consumer health modifications. Three primary
      areas of interest and benefit included socialization and support, education and
      information, and motivation to change. The Wellness Education Group Intervention
      (WEGI) can serve as a model for wellness education with adults in similar
      communities.

PMID- 21736464
TI  - Psychometric properties of a measure of acceptance of long-standing health
      problems.
AB  - Acceptance of chronic illness is important for health promotion and for improving
      the quality of life of elders with chronic conditions. Thus, a reliable and valid
      measure of acceptance is needed for this population. Currently available measures
      of acceptance do not focus specifically on accepting chronic conditions. This
      study of 176 elders with chronic conditions examined the psychometric properties
      of an adapted measure of acceptance--the Ideas About Long-Standing Health
      Problems (IALHP) questionnaire. Although the findings provided beginning evidence
      for internal reliability and construct validity to support its potential
      usefulness in elders, further scale development is recommended.

PMID- 21736465
TI  - Ethnographic research into nursing in acute adult mental health units: a review.
AB  - Acute inpatient mental health units are busy and sometimes chaotic settings, with
      high bed occupancy rates. These settings include acutely unwell patients, busy
      staff, and a milieu characterised by unpredictable interactions and events. This
      paper is a report of a literature review conducted to identify, analyse, and
      synthesize ethnographic research in adult acute inpatient mental health units.
      Several electronic databases were searched using relevant keywords to identify
      studies published from 1990-present. Additional searches were conducted using
      reference lists. Ethnographic studies published in English were included if they
      investigated acute inpatient care in adult settings. Papers were excluded if the
      unit under study was not exclusively for patients in the acute phase of their
      mental illness, or where the original study was not fully ethnographic. Ten
      research studies meeting our criteria were found (21 papers). Findings were
      grouped into the following overarching categories: (1) Micro-skills; (2)
      Collectivity; (3) Pragmatism; and (4) Reframing of nursing activities. The
      results of this ethnographic review reveal the complexity, patient-orientation,
      and productivity of some nursing interventions that may not have been observed or
      understood without the use of this research method. Additional quality research
      should focus on redefining clinical priorities and philosophies to ensure
      everyday care is aligned constructively with the expectations of stakeholders and
      is consistent with policy and the realities of the organisational setting. We
      have more to learn from each other with regard to the effective nursing care of
      inpatients who are acutely disturbed.

PMID- 21736466
TI  - Motivational interviewing: a valuable tool for the psychiatric advanced practice
      nurse.
AB  - Motivational Interviewing (MI) is well known and respected by many health care
      professionals. Developed by Miller and Rollnick (2002) , it is a way to promote
      behavior change from within and resolve ambivalence. MI is individualized and is
      most commonly used in the psychiatric setting; it is a valuable tool for the
      Psychiatric Advanced Nurse Practice Nurse. There are many resources that talk
      about what MI is and the principles used to apply it. However, there is little
      information about how to incorporate MI into a clinical case. This article
      provides a summary of articles related to MI and discusses two case studies using
      MI and why advanced practice nurses should use MI with their patients.

PMID- 21736467
TI  - Perceived stress among nursing staff in psychiatric inpatient care: the influence
      of perceptions of the ward atmosphere and the psychosocial work environment.
AB  - The aims of this study were to investigate (1) perceived stress as felt by the
      nursing staff working in psychiatric inpatient care, (2) possible differences
      between nurses and nurse assistants, and (3) associations among individual
      characteristics, the ward atmosphere, the psychosocial work environment, and
      perceived stress. Ninety-three members of the nursing staff completed three
      instruments--one each measuring perceived stress, the ward atmosphere, and the
      psychosocial work environment. There were no differences among the staff groups
      concerning perceived stress. Multivariate analysis showed that the ward
      atmosphere factor "Involvement" and the psychosocial work environment factor
      "Role Clarity" were indicators of perceived stress. Improvements in these factors
      could help to prevent stress among the staff.

PMID- 21736468
TI  - Scratching beneath the surface: influencing factors on nurses' attitudes toward
      the use of seclusion.
AB  - Reducing the use of seclusion is now widely identified as a quality issue for
      mental health services and reflects recognition of the detrimental impact of
      seclusion on consumers of services. Despite this, the research evidence suggests
      that nurses continue to support the use of seclusion in order to maintain a safe
      environment. The aim of this study was to consider how factors such as
      Therapeutic Optimism, Job Satisfaction, and Burnout might relate to nurses'
      attitudes toward seclusion. The Heyman Attitudes to Seclusion Survey, Elsom
      Therapeutic Optimism Scale, Maslach's Burnout Inventory, and Minnesota
      Satisfaction Questionnaires were completed by 123 nurses employed in one of eight
      participating mental health services. Data analysis included Spearman's rho and
      independent-samples t-tests statistics. The findings suggested several
      significant relationships between attitudes toward seclusion and therapeutic
      optimism, job satisfaction, and burnout. Participants with higher optimism
      scores, high intrinsic motivation, low emotional exhaustion, and high personal
      accomplishment were more likely to respond negatively to the use of seclusion.
      This research enhances our understanding of attitudes toward seclusion and may
      assist in the development of interventions to influence more positive attitudes.

PMID- 21736469
TI  - Waiting for oblivion: women's experiences with electroshock.
AB  - This article presents findings and analysis stemming from a two-year qualitative
      study that explored, in their own voices, women's lived experience of
      electroshock. Feminist standpoint theory frames and provides the moorings for
      both the validity and methodology of this woman-centered inquiry. In addition,
      nurses' experiences with and views of ECT are explored and compared to the
      experiences reported by the women recipients themselves. Vulnerability and
      disconnection as emergent themes are presented for the nursing profession's sober
      consideration. The nurses interviewed believed electroshock culminated in a net
      gain for patients, but for the majority of the women interviewed, electroshock
      resulted in damage and devastating loss. This article closes with pressing
      questions for nurses to ask ourselves as we enter the second decade of this new
      and promising millennium.

PMID- 21736470
TI  - The ECT Nursing Literature.

PMID- 21736471
TI  - An evidence-based response to "electroshock, a discerning review of the nursing
      literature".

PMID- 21736472
TI  - Defining exercise in contrast to physical activity.

PMID- 21736473
TI  - Leave your dignity, identity, and day clothes at the door: the persistence of
      pyjama therapy in an age of recovery and evidence-based practice.

PMID- 21736475
TI  - Second malignant neoplasms following childhood cancer: a study of a recent cohort
      (1987-2004) from the childhood cancer registry of the Rhone-Alpes region
      (ARCERRA) in France.
AB  - Studies of second malignant neoplasms (SMNs) in childhood are generally conducted
      in old cohorts. The aim of this study was to determine the actual incidence of
      all SMNs in a recent cohort. The authors studied a cohort of 2907 children
      included in the population-based Childhood Cancer Registry of the Rhone-Alpes
      Region for a first cancer diagnosed between 1987 and 2004. Total follow-up was
      22,722 person-years, with a median follow-up of 9.8 years (range, 00.0-22.8
      years). Fifty-four SMNs were reported in 52 patients. Overall median latency was
      5.9 years. Cumulative incidence rates were 2.2% at 10 years and 3.9% at 15, with
      an overall standardized incidence ratio (SIR) of 13.9 (95% confidence interval
      [CI], 10.4-18.3) and absolute excess risk of 2.2. The SMNs were 12 thyroid
      carcinomas (SIR 57.1); 9 bone tumors (SIR 32.0); 8 leukemias (SIR 11.9); 5
      lymphomas, all related to Epstein-Barr virus following allograft, (SIR 6.7); 5
      CNS tumors (SIR 10.5); 4 soft tissue sarcomas (SIR 17.4); 4 carcinomas (no breast
      cancer); and 7 other cancers. Twelve SMNs appeared after total body irradiation,
      16 after focal radiotherapy, and 8 leukemias after chemotherapy. The risk of
      secondary cancer was highest after retinoblastomas (SIR 41.8), Hodgkin lymphomas
      (SIR 20.8), leukemias (SIR 18.4), soft tissue sarcomas, CNS tumors, and bone
      tumors. These recent cohort findings show, on one hand, a high incidence of SMNs
      but do not capture breast cancers because of the relatively short follow-up and,
      on the other hand, a different distribution of first and second cancers.

PMID- 21736476
TI  - A case with unexplained bleeding from multiple sites: munchausen syndrome by
      proxy.
AB  - Munchausen syndrome by proxy (MBP) is an extreme form of child abuse where
      children were unnecessarily treated or investigated for medical conditions that
      were falsified by their caregivers. Here the authors report a 16-year-old female
      with the complaints of bleeding from multiple and unusual sites, including
      hemoptysis, hematuria, bloody tears, and bloody nipple discharge, all of which
      are only witnessed by her mother. Extensive investigation revealed no organic
      etiologies for bleeding. The diagnosis of MBP was put by a multidisciplinary
      team. The diagnosis of MBP must be kept in mind in conditions where there is no
      underlying organic pathology in a bleeding patient.

PMID- 21736477
TI  - Human infections with Dicrocoelium dendriticum in Kyrgyzstan: the tip of the
      iceberg?
AB  - Dicrocoelium dendriticum is the causative agent of a rare food-borne zoonosis of
      the human biliary tract, dicrocoeliasis, for which few human prevalence data are
      available. Infection occurs through the ingestion of ants containing
      metacercariae, whereas pseudo-infections (presence of D. dendriticum eggs in
      stool in the absence of adult worms) are due to the consumption of infected
      animal liver. Here, results from a cross-sectional survey carried out among 138
      children aged 2-15 yr in a peri-urban area of Kyrgyzstan are reported. Each child
      provided 1 stool sample that was subjected to the FLOTAC technique. Eggs of D.
      dendriticum were diagnosed in 11 children (prevalence 8.0%; 95% confidence
      interval 4.5-13.7%). Although no distinction could be made between true and
      pseudo-infections, the prevailing animal husbandry system and the diet and
      hygienic conditions of the study area suggest that the social-ecological system
      in Kyrgyzstan is conducive for human transmission of D. dendriticum. There is a
      need to investigate the epidemiology of dicrocoeliasis in Kyrgyzstan, placing
      emphasis on the distinction between true and pseudo-infections.

PMID- 21736478
TI  - Ultra-high-yield manufacture of red blood cells from hematopoietic stem cells.
AB  - Provision of a safe and secure supply of transfusible red blood cells (RBC) is a
      major global health challenge, and it has been proposed that manufactured RBC
      could help to alleviate the constraints of the current donor system. Several
      substantial challenges must be addressed for this approach to be feasible. At the
      most basic level, this relates to the large quantities of cells that are
      required: is there sufficient biological capacity, and is it possible to produce
      RBC using large-scale processes? While it has been demonstrated that, in
      principle, up to 5 units of RBC could be generated from a single donation of
      umbilical cord blood (UCB) hematopoietic stem cells, such yields are insufficient
      to supply demand and existing culture methods are unsuitable for large-scale
      manufacture. Given the capacity of the hematopoietic system in vivo, we reasoned
      that an optimized process should give rise to much larger quantities of RBC than
      previously reported. We successfully developed a robust ultra-high-yield RBC
      expansion process capable of producing over 500 units of RBC per UCB donation
      using fully defined culture medium. We obtained near-pure populations of
      reticulocytes with an enucleation frequency of >90%, mean cell hemoglobin content
      of 30.8 pg/cell, and mean cell volume of 133 fL. We also show that RBC can be
      efficiently produced in agitated bioreactor systems, demonstrating that no
      fundamental barriers exist to the manufacture of RBC using large-scale
      approaches.

PMID- 21736479
TI  - Influence of processed sugarcane bagasse on the microbial, nutritional,
      rheological and quality characteristics of biscuits.
AB  - Sugarcane bagasse, a dietary fiber-rich by-product of the sugar industry (70-75%)
      and having negligible protein and fat content, was treated with acid, alkali and
      steaming to reduce the microbial load. Steaming was effective in making the
      bagasse microbiologically safe. The processed bagasse (5-15%) was used in the
      rheological studies and in the preparation of soft dough biscuits. Glucose
      (hexose), arabinose and xylose (pentose) were present, whereas rhamnose, mannose
      and galctose were not traced in all of the bagasse samples. Farinograph
      characteristics of wheat flour-bagasse blends showed that the mixing profile
      weakened with addition of bagasse. Processed bagasse also affected the pasting
      characteristics indicating starch dilution on incorporation of bagasse, as
      indicated by sensory characteristics. Biscuits prepared from steamed bagasse
      (10%) along with additives were highly acceptable. Results indicated that high
      fiber biscuits can be prepared by replacing wheat flour with steamed bagasse at a
      10% level.

PMID- 21736480
TI  - Promoting influence of combinations of amchur, beta-carotene-rich vegetables and
      Allium spices on the bioaccessibility of zinc and iron from food grains.
AB  - Deficiencies of iron and zinc among the population dependent on plant foods
      necessitate strategies to maximize their bioavailability. In this context,
      specific combinations of promoters of iron and zinc bioaccessibility-namely,
      amchur (0.75 g/10 g), beta-carotene-rich vegetables (2.5 g/10 g) and Allium
      spices (1.5 g/10 g)-were evaluated for a possible additive/synergistic effect on
      the bioaccessibility of iron and zinc from food grains. The positive influence on
      the bioaccessibility of iron was additive in the case of combinations of amchur
      carrot, amchur-garlic, onion-carrot, and onion-amaranth in a few specific grains.
      Positive influence on the bioaccessibility of iron was even synergistic for
      combinations of amchur-onion and amchur-garlic in a few grains. The influence of
      amchur-garlic and amchur-onion was additive while the combination of amchur
      amaranth and amchur-garlic produced a synergistic-promoting influence on zinc
      bioaccessibility in a few instances. This observation would be useful in evolving
      dietary strategies to maximize the bioavailability of minerals from grains.

PMID- 21736481
TI  - Subarachnoid clonidine for labor pain: the two sides of the coin.

PMID- 21736482
TI  - Takayasu's arteritis in pregnancy and obstetric anesthesia.

PMID- 21736483
TI  - Oxygen concentration dependence of lipid peroxidation and lipid-derived radical
      generation: application of profluorescent nitroxide switch.
AB  - Lipid-derived radicals and peroxides are involved in the pathogenesis of
      oxidative stress diseases and, although lipid peroxide production is a required
      reaction between a lipid radical and molecular oxygen, a useful lipid radical
      detection method has remained tentative. Also, the effect of oxygen concentration
      on lipid peroxide production must be considered because of the hypoxic conditions
      in cancer and ischemic regions. In this study, the focus was on nitroxide
      reactivity, which allows spin trapping with carbon-centred radicals via radical
      radical reactions and fluorophore quenching through interactions with nitroxide's
      unpaired electron. Thus, the aim here was to demonstrate a useful detection
      method for lipid-derived radicals as well as to clarify the effects of oxygen
      concentration on lipid peroxide production using profluorescent nitroxide. This
      latter compound reacted with lipid-derived radicals in a manner inversely
      dependent on oxygen concentration, resulting in fluorescence due to alkoxyamine
      formation and, conversely, lipid peroxide concentrations decreased with lower
      oxygen in the reaction system. Furthermore, nitroxide inhibited lipid peroxide
      production and stopped oxygen consumption in the same solution. These results
      suggested that the novel application of profluorescent nitroxide could directly
      and sensitively detect lipid-derived radicals and that radical and peroxide
      production were dependent on oxygen concentration.

PMID- 21736484
TI  - Endoplasmic reticulum stress induces retinal endothelial permeability of
      extracellular-superoxide dismutase.
AB  - The aim of this study was to determine the reasons why the intravitreal level of
      extracellular-superoxide dismutase (EC-SOD) increases in proliferative diabetic
      retinopathy patients by the investigation of two possibilities: first, change of
      EC-SOD expression in the retina; and secondly, leakage of EC-SOD through the
      endothelial monolayer by the treatment with endoplasmic reticulum (ER) stress
      inducers because ER stress is known to be involved in the vascular impairment in
      diabetic retinopathy. Intravitreous injection of tunicamycin in mice increased
      the permeability of tracer dye across retinal blood vessels while the retinal EC
      SOD mRNA level was not changed. The leakage of EC-SOD through the retinal
      endothelial cell layer was elevated by the treatment with thapsigargin or
      tunicamycin. The expression of claudin-5 was significantly decreased by the
      treatment with the ER stress inducers. These phenomena were significantly
      suppressed by the pre-treatment of endothelial cells with a chemical chaperone 4
      phenylbutyric acid. Our observations suggest that ER stress leads to the down
      regulation of claudin-5 among tight junction proteins and may induce the
      elevation of endothelial permeability and leakage of EC-SOD into the vitreous
      body.

PMID- 21736485
TI  - Ecological diversity of Bartonella species infection among dogs and their owner
      in Virginia.
AB  - Bartonella species comprise a genus of gram-negative, fastidious, intracellular
      bacteria that have been implicated in association with an increasing spectrum of
      disease manifestations in dogs and human patients. In this study, chronic canine
      and human disease, for which causation was not diagnostically defined, were
      reported by the breeder of a kennel of Doberman pinschers. In addition to other
      diagnostic tests, serology, polymerase chain reaction, and enrichment blood
      culture were used to assess the prevalence of Bartonella sp. infection in the
      dogs and their owner. From five dogs, Bartonella vinsonii subsp. berkhoffii
      genotype I, multiple Bartonella henselae strains, and a species most similar to
      Candidatus B. volans, a rodent-associated Bartonella sp., were amplified and
      sequenced from biopsy tissues, cerebrospinal fluid, or blood enrichment cultures.
      The owner was bacteremic with B. vinsonii subsp. berkhoffii genotype I, the same
      subsp. and genotype detected in one of her dogs. These results further emphasize
      the ecological complexity of Bartonella sp. transmission in nature.

PMID- 21736486
TI  - Polymerase chain reaction confirmation of Babesia canis canis and Anaplasma
      phagocytophilum in dogs suspected of babesiosis in Slovakia.
AB  - Canine babesiosis was considered an imported tick transmitted disease until the
      first case of autochthonous canine babesiosis in Slovakia was described in 2002.
      Since then, the number of cases kept increasing every year. The causative agent
      of babesiosis in dogs is not yet characterized; therefore, the aim of our study
      was to determine the agent and the rate of infection in the vector tick D.
      reticulatus in Slovakia. Babesia canis canis was detected in 80 out of 87 blood
      samples from dogs with clinical manifestations of babesiosis. Six dogs suspected
      of babesiosis tested positive for presence of Anaplasma phagocytophilum, and one
      mixed infection of B. c. canis and A. phagocytophilum was detected. B. c. canis
      was detected in 35.6% questing adults of D. reticulatus. The obtained sequences
      from blood samples showed 99.7% and from D. reticulatus, 99.4% similarity with
      the B. c. canis (AY072926) from dogs infected in Croatia. In our study, we
      characterized the agent of canine babesiosis from blood samples of naturally
      infected dogs and D. reticulatus, the vector tick. Further, the presence of A.
      phagocytophilum, bacterium responsible for the canine granulocytic anaplasmosis,
      was recorded in dogs for the first time in Slovakia.

PMID- 21736487
TI  - Serologic evidence of avian metapneumovirus infection among adults occupationally
      exposed to Turkeys.
AB  - Genetically similar, the avian metapneumovirus (aMPV) and the human MPV (hMPV)
      are the only viruses in the Metapneumovirus genus. Previous research demonstrated
      the ability of hMPV to cause clinical disease in turkeys. In this controlled,
      cross-sectional, seroepidemiological study, we examined the hypothesis that aMPV
      might infect humans. We enrolled 95 adults occupationally exposed to turkeys and
      82 nonexposed controls. Sera from study participants were examined for antibodies
      against aMPV and hMPV. Both in bivariate (OR=3.2; 95% CI: 1.1-9.2) and in
      multivariate modelling adjusting for antibody to hMPV (OR=4.1; 95% CI: 1.3-13.1),
      meat-processing workers were found to have an increased odds of previous
      infection with aMPV compared to controls. While hMPV antibody cross-reactivity is
      evident, these data suggest that occupational exposure to turkeys is a risk
      factor for human infection with aMPV. More studies are needed to validate these
      findings, to identify modes of aMPV transmission, and to determine risk factors
      associated with infection.

PMID- 21736488
TI  - Detection of Borrelia burgdorferi Sensu Lato and Anaplasma phagocytophilum in
      small mammals and ectoparasites in Hungary.
AB  - The aim of our study was to investigate the presence of Borrelia burgdorferi
      sensu lato (s.l.) and Anaplasma phagocytophilum in small mammals and ticks using
      polymerase chain reaction and to gain information about the prevalence and
      possible coexistence of these pathogens at a selected site in Hungary. Two
      hundred seventy-seven small mammals were trapped in South-Eastern Hungary during
      2009. Tissue samples and a total of 831 ectoparasites (Ixodes ricinus, Ixodes
      acuminatus, Haemaphysalis concinna, Ctenophtalmus assimilis, and Nosopsyllus
      fasciatus) were collected from small mammals. One thousand one hundred and six I.
      ricinus and 476 H. concinna were collected from the vegetation during the
      investigation. Neither A. phagocytophilum nor B. burgdorferi s.l. was detected in
      any of the mammal tissue samples. A. phagocytophilum was not found in ticks
      collected from small mammals. Very low minimum prevalence was found for all
      pathogens (0.62% for Borrelia afzelii in ticks collected from small mammals, and
      0.57%, 0.06%, and 0.19% for A. phagoctyophilum, B. afzelii, and Borrelia garinii,
      respectively, in questing ticks). The present study is the first report of
      borreliae from I. acuminatus and H. concinna from Hungary.

PMID- 21736489
TI  - Using wild white-tailed deer to detect eastern equine encephalitis virus activity
      in Maine.
AB  - Serum from 226 free-ranging white-tailed deer (Odocoileus virginianus) was
      screened for Eastern Equine Encephalitis Virus (EEEV) antibodies using plaque
      reduction neutralization tests. EEEV antibodies were detected in 7.1% of samples.
      This is the first time EEEV antibodies have been detected in O. virginianus
      populations in the state of Maine (ME). The highest percentage of EEEV positive
      sera was in Somerset County (19%) in central ME, and this is the first time that
      EEEV activity has been detected in that County. EEEV RNA was not detected in any
      of the 150 harvested deer brain samples submitted to the ME Department of Inland
      Fisheries and Wildlife as a part of screening for Chronic Wasting Disease. This
      suggests that screening deer brains is not an efficient method to detect EEEV
      activity. For each serum sample tested, the geographic location in which the deer
      was harvested was recorded. Significant spatial clustering of antibody-positive
      sera samples was not detected. Relative to seronegative deer, seropositive deer
      were slightly more likely to be harvested in nonforested areas compared with
      forested areas. Results indicate that screening of free-ranging deer sera can be
      a useful tool for detecting EEEV activity in ME and other parts of North America.

PMID- 21736490
TI  - Crimean-Congo hemorrhagic fever virus in ticks collected from humans, livestock,
      and picnic sites in the hyperendemic region of Turkey.
AB  - During June and July 2007, about 3125 adult ticks were collected from humans,
      animals, and vegetation in a hyperendemic region (Sivas and Tokat) of Turkey. A
      total of 2193 ticks were pooled in 225 pools and screened for the Crimean Congo
      hemorrhagic fever virus (CCHFV) presence by antigen-capture enzyme-linked
      immunosorbent assay. Infection rates were calculated as the maximum likelihood
      estimation with 95% confidence intervals (CI). The dominant tick species was
      found to be Hyalomma marginatum with the following infestation rates in human,
      cattle and sheep, respectively: 47.43%, 66.07%, and 30.12%. Maximum likelihood
      estimation values of CCHFV in H. marginatum ticks collected from human, cattle,
      and sheep were 0.91% (CI 0.05-4.42), 2.10% (CI 1.12-3.64), and 3.11% (CI 1.18
      6.87), respectively. CCHFV antigens were also demonstrated in Hyalomma excavatum,
      Haemaphysalis parva, and Boophilus annulatus ticks collected from cattle and
      Rhipicephalus bursa ticks from sheep. Our results suggest that the studied area
      might maintain its endemic properties in the near future unless effective tick
      control measures are implemented.

PMID- 21736491
TI  - Examination of a virulence mutant uncovers the ribosome biogenesis regulatory
      protein of Toxoplasma gondii.
AB  - Several insertional mutants identified in a screen for Toxoplasma gondii that
      were defective in establishing a chronic infection had a common site of plasmid
      insertion. This insertion site was determined to be 43 bp upstream of the
      transcription initiation site of a gene whose predicted product has homology to
      ribosome biogenesis regulatory protein Rrs1p, an essential protein required for
      ribosome biogenesis in Saccharomyces cerevisiae. Northern blot analysis of this
      locus, termed TgRRS1 , showed that in the C3 mutant, the full-length transcript
      is down-regulated and at least 1 new smaller transcript is present. Restoration
      of the intact predicted promoter and locus to TgRRS1 insertional mutant strain C3
      did not restore brain cyst formation to the levels of the parent strain. Epitope
      tagged TgRRS1 was found to localize to the parasite nucleolus, in an area
      corresponding to the granular component region. TgRRS1 can serve as a marker for
      the sub-nucleolar granular component region of T. gondii.

PMID- 21736492
TI  - Prevalence and severity of vestibular recession in mandibular incisors after
      orthodontic treatment.
AB  - OBJECTIVE: To assess the prevalence and severity of vestibular gingival recession
      of mandibular incisors after orthodontic treatment and to evaluate possible
      contributing factors. MATERIALS AND METHODS: From the record pool of patients who
      completed orthodontic treatment from 1999-2006 at the Department of Orthodontics,
      University of Oslo, Norway, 588 patients fulfilled the inclusion criteria.
      Intraoral color slides were used for the evaluation of gingival recessions (based
      on Miller classification), presence of visible plaque, and gingival inflammation.
      Cephalometric radiographs were used to assess the sagittal intermaxillary
      relation, mandibular and intermaxillary angles, and the position of the lower
      incisors. A control group was drawn from the same pool of 588 patients. All
      statistical analyses were performed using SPSS. RESULTS: The prevalence of
      gingival recessions after orthodontic treatment was 10.3%. Most (8.6%) were
      classified as Miller Class I, and 1.7% were classified as Miller Class II.
      Gingival recession was predominantly found on central incisors. Reduction of the
      sagittal intermaxillary angle and retroclination of the lower incisors was
      correlated with the development of a more severe gingival recession. CONCLUSIONS:
      The present study indicates that vestibular gingival recession of mandibular
      incisors after orthodontic treatment is of minor prevalence and severity. The
      presence of gingival recession or retroclination of the incisors with mesial
      basal relations increases the risk of more severe gingival recession.

PMID- 21736493
TI  - Evaluation of insulin-like growth factor-1 in Indian growth hormone-deficient
      children on growth hormone therapy.
AB  - OBJECTIVE: To evaluate the impact of recombinant human growth hormone therapy
      (GHT) on serum insulin-like growth factor 1 (IGF-1) concentrations in Indian
      children with growth hormone deficiency. METHODS: Data on anthropometry and serum
      IGF-1 concentrations were collected from 28 growth hormone-deficient prepubertal
      children (8.6 +/- 2.9 years) on growth hormone therapy, 6 monthly over the period
      of 2 years. RESULTS: Height z-scores showed a steady increase from baseline to 24
      months. However, IGF-1 z-scores showed a plateau after the first 6 months and
      then a small dip followed by a rise. The pattern of increase of IGF-1 z-scores
      was dissimilar to that of the height z-scores. CONCLUSION: The change in serum
      IGF-1 z-scores in response to GHT in Indian children may not be a good indicator
      for monitoring growth hormone responsiveness.

PMID- 21736494
TI  - Effect of chronic regular exercise on serum ischemia-modified albumin levels and
      oxidative stress in type 2 diabetes mellitus.
AB  - Objectives. Our aim was to determine the effect of chronic regular exercise on
      ischemia-modified albumin (IMA) levels and oxidative stress in type 2 diabetes
      mellitus (DM). Design and methods. Sixty patients with type 2 DM were randomly
      divided into two groups as exercise (17 M, 13 F) and non-exercise (12 M, 18 F)
      groups, each consisting of 30 patients. The exercise group underwent a 3-month
      aerobic regular exercise consisting of moderate-intensity power walking. The non
      exercise subjects remained sedentary throughout the study period. Serum total
      antioxidant status (TAS), total oxidant status (TOS), and IMA levels of the
      groups were determined at baseline and 3 months later. Results. There was no
      significant change in TOS and IMA levels of exercise group but TAS levels were
      significantly increased (p < 0.05). Also, postexercise systolic (p < 0.001) and
      diastolic (p < 0.05) blood pressures of the exercise group were significantly
      lower than the baseline values. In addition, there was no significant change in
      TAS and TOS levels of the non-exercise group; however, IMA levels were
      significantly increased (p < 0.01). Conclusion. We have shown, for the first
      time, that exercise prevents increase in IMA levels in type 2 DM which might have
      resulted from increased levels of TAS and reduces the risk of ischemia in these
      patients. These findings show that chronic exercise is beneficial in the
      prevention of oxidative stress in patients with type 2 DM as documented by
      decreased IMA levels.

PMID- 21736495
TI  - Changes in prooxidant-antioxidant balance in tissues of rats following long-term
      hyperglycemic status.
AB  - INTRODUCTION: Reactive oxygen species play an important role in the pathogenesis
      of organ damage in diabetes mellitus. Streptozotosin (STZ) is a commonly employed
      compound to produce diabetes mellitus and these animals exhibit most of diabetic
      complications. METHODS: In our study, diabetes was induced by a single
      intraperitoneal injection of STZ at a dose of 50 mg/kg in rats and they were
      killed 12 weeks after STZ. Endogenous lipid peroxide levels, enzymatic and non
      enzymatic antioxidants were measured in liver, heart, kidney, brain, and testis
      tissues to investigate the effect of long-term hyperglycemic state. The
      susceptibility of diabetic tissues to oxidative stress was also examined in in
      vitro oxidizing system containing ascorbic acid and iron. RESULTS: We found that
      prooxidant and antioxidant balance has changed in favor of prooxidation in the
      tissues of diabetic rats. The susceptibility of liver to oxidative stress
      increased; however, this susceptibility did not change in heart, kidney, brain,
      and testis of diabetic rats. CONCLUSION: Our results indicate that long-term
      hyperglycemic state disturbs hepatic prooxidant-antioxidant balance at an earlier
      period and more pronouncedly than other tissues.

PMID- 21736496
TI  - Dynamics of septin ring and collar formation in Saccharomyces cerevisiae.
AB  - Although the septin ring and collar in budding yeast were described over 20 years
      ago, there is still controversy regarding the organization of septin filaments
      within these structures and about the way in which the ring first forms and about
      how it converts into a collar at the mother-bud neck. Here we present
      quantitative analyses of the recruitment of fluorescently-tagged septins to the
      ring and collar through the cell cycle. Septin ring assembly began several
      minutes after polarity establishment and this interval was longer in daughter
      than in mother cells, suggesting asymmetric inheritance of septin regulators.
      Septins formed an initial faint and irregular ring, which became more regular as
      septins were recruited at a constant rate. This steady rate of septin recruitment
      continued for several minutes after the ring converted to a collar at bud
      emergence. We did not detect a stepwise change in septin fluorescence during the
      ring-to-collar transition. After collar formation, septins continued to
      accumulate at the bud neck, though at a reduced rate, until the onset of
      cytokinesis when the amount of neck-localized septins rapidly decreased.
      Implications for the mechanism of septin ring assembly are discussed.

PMID- 21736497
TI  - A method of measuring the interaction between skin temperature and humidity on
      skin vascular endothelial function in people with diabetes.
AB  - BACKGROUND: A core defect in people with Type 2 Diabetes is endothelial
      dysfunction. This defect permeates all organ systems in the body including the
      ability of the skin to protect itself from thermal injuries by an appropriate
      increase in skin circulation. Most studies on the local response to heating have
      been done with dry heat sources. Recent data show that endothelial function is
      improved in people with diabetes with moist heat. Little is known about 'how'
      moist heat must be or the mechanisms on why moist heat triggers a better blood
      flow response than dry heat. METHODS: In the present investigation, a device was
      developed to provide variable temperature air and variable humidity as an aid to
      study the dynamics of the skin circulatory response to heat in people with
      diabetes. The device consisted of a water bath used to heat air and an air dryer
      and air bubbler to generate dry and moist air, respectively, at a fixed
      temperature. The air could then be mixed and the temperature stabilized to
      produce a variable temperature and humidity air source to expose the skin to in
      people with diabetes. RESULTS: The device was validated at different air
      temperatures and humidities and tested on four subjects to assess operation. The
      air flows, temperatures and humilities were stable with less than a 5%
      coefficient of variation. CONCLUSIONS: Testing on humans showed that there
      appeared to be a linear relationship between air humidity and blood flow at a
      given air temperature exposed to the skin.

PMID- 21736498
TI  - Twin versus singleton pregnancies complicated by preterm premature rupture of
      membranes.
AB  - OBJECTIVE: To compare latency period, infectious morbidity, neonatal morbidity
      and neonatal mortality in twin versus singleton pregnancies complicated by
      preterm premature rupture of membranes (PPROM) remote from term. METHODS: A
      retrospective, matched cohort study comparing 41 twin and 82 singleton
      pregnancies complicated by PPROM between 24-0/7 and 31-6/7 weeks' gestation. The
      data were obtained by reviewing maternal and neonatal charts. RESULTS: The median
      latency periods were 3.6 days (interquartile range 1.5-13.9 days) for twins and
      6.2 days (interquartile range 2.9-11.8 days) for singletons (p = 0.86). Twins
      were less likely to be complicated by clinical chorioamnionitis when compared
      with singletons (4/41 [9.8%] vs. 19/82 [23.2%], relative risk [RR] 0.42, 95%
      confidence interval [CI] 0.18-0.96). Histological evidence of chorioamnionitis
      was also lower in twins compared with singletons (14/39 [35.9%] vs. 46/68
      [67.7%], RR 0.56, 95% CI, 0.34-0.92). These differences persisted after adjusting
      for race, insurance status, latency period and route of delivery. Neonatal
      morbidity and mortality rates were similar between the two groups. CONCLUSIONS:
      There was not a statistically significant difference in the latency periods for
      twin and singleton pregnancies complicated by PPROM. Clinical chorioamnionitis
      and histological evidence of infection were significantly less common in twins
      compared with singletons.

PMID- 21736499
TI  - Opening the black box of cancer patients' quality-of-life change assessments: a
      think-aloud study examining the cognitive processes underlying responses to
      transition items.
AB  - Transition items are a popular approach to determine the clinical significance of
      patient-reported change. These items assume that patients (1) arrive at a change
      evaluation by comparing posttest and pretest functioning, and (2) accurately
      recall their pretest functioning. We conducted cognitive think-aloud interviews
      with 25 cancer patients prior to and following radiotherapy. Two researchers
      independently analysed their responses using an analysis scheme based on
      cognitive process models of Tourangeau et al. and Rapkin and Schwartz. In 112 of
      the 164 responses to transition items, patients compared current and prior
      functioning. However, in 104 of these responses, patients did not refer to their
      functioning at pretest and/or posttest according to transition design's first
      assumption, but rather used a variety of time frames. Additionally, in 79
      responses, the time frame employed and/or description of prior functioning
      provided differed from those employed in the corresponding pretest items.
      Transition design's second assumption was therefore not in line with the
      patients' cognitive processes. Our findings demonstrate that in interpreting
      transition assessments, one needs to be aware that patients provide change
      assessments, which are not necessarily based on the cognitive processes intended
      by researchers and health care providers.

PMID- 21736500
TI  - 'It's like there are two people in my head': a phenomenological exploration of
      anorexia nervosa and its relationship to the self.
AB  - This study explores the lived experience of anorexia nervosa from the perspective
      of those who use pro-recovery websites for eating disorders. Fourteen people
      participated in an online focus group or an e-interview. Data were analysed using
      interpretative phenomenological analysis. Participants described their disorder
      as a functional tool for avoiding and coping with negative emotions, changing
      their identity and obtaining control. A central theme was the experience of an
      'anorexic voice' with both demonic and friendly qualities. This voice felt like
      an external entity that criticised individuals and sometimes dominated their
      sense of self, particularly as anorexia nervosa got worse. Applying dialogical
      theory suggests a new model of anorexia nervosa, where the anorexic voice is a
      self-critical position, which disagrees with and attempts to dominate the more
      rational self. It is suggested that to move on from anorexia nervosa, the
      individual needs to address his/her anorexic voice and develop a new dominant
      position that accepts and values his/her sense of self.

PMID- 21736501
TI  - Enhanced insulin resistance in diet-induced obese rats exposed to fine particles
      by instillation.
AB  - CONTEXT: Epidemiological studies indicate that diabetes is a sub-population at
      risk for particulate matter (PM)-associated cardiovascular disease (CVD). Recent
      animal studies suggested PM might impair glucose tolerance, which may lead to
      CVD. However, the mechanism remains unclear. OBJECTIVE: To investigate further
      the PM effect on insulin resistance (IR) in obese and healthy rats. MATERIALS AND
      METHODS: Male Sprague-Dawley rats were fed with either a high fat diet (HFD) or
      normal chow diet (NCD) for 6 weeks. Both groups were then further assigned to
      receive PM(10), PM(2.5) or normal saline (n = 6 per group) by intratracheal
      instillation (IT) once per week for 3 weeks. Fasting glucose and insulin were
      measured and homeostasis model assessment-insulin resistance (HOMA-IR) was used
      to assess IR. Biochemistry tests and lipids profile were examined at sacrifice.
      The markers of fibrinogen and [nitrate+nitrite], an indicator of nitric oxide
      (NO) production, C-reactive protein (CRP) and white blood counts (WBCs) in
      peripheral blood were also determined. RESULTS: Body weight, insulin and HOMA-IR
      of HFD rats were significantly increased compared with a NCD after 6 weeks. In
      HFD rats, PM(2.5) increased HOMA-IR after first IT and further increased HOMA-IR
      at the end of exposure. However, this increase was not observed in NCD rats and
      after PM(10) exposure. Increased fibrinogen was also noted after chronic PM(2.5)
      exposure in both HFD and NCD rats. DISCUSSION AND CONCLUSION: Exposure to PM(2.5)
      enhanced IR in HFD rats but not in NCD rats. Obese subjects with IR may be a
      susceptible population to particulate air pollution.

PMID- 21736502
TI  - Total skin electron beam therapy for cutaneous T-cell lymphoma: a nationwide
      cohort study from Denmark.
AB  - BACKGROUND: Total skin electron beam therapy (TSEBT) is an effective palliative
      treatment for cutaneous T-cell lymphoma (CTCL). In the present study we reviewed
      the clinical response to TSEBT in Danish patients with CTCL. MATERIAL AND
      METHODS: This retrospective study included 35 patients with CTCL treated with
      TSEBT in Denmark from 2001 to 2008 and followed for a median time of 7.6 months
      (range 3 days-3.7 years). Twenty five patients were treated with high-dose (30
      Gy) and 10 patients in a protocol with low-dose (4 Gy) TSEBT. RESULTS: Patients
      treated with low-dose therapy had inadequate response to treatment compared to
      patients treated with high-dose. Consequently the study with low-dose was
      discontinued and published. In patients treated with high-dose the overall
      response rate was 100%. Complete response (CR) rate was 68% and CR occurred after
      a median time of 2.1 months (range 1.8 months-2.0 years). We found no difference
      in CR rate in patients with T2 (66.7%) and T3 disease (78.6%) (p = 0.64).
      Following CR 82.4% relapsed at a median time of four months (range 12 days-11.5
      months). Relapse-free-survival was similar in patients with T2 and T3 disease (p
      = 0.77). Progressive disease (PD) was experienced in 28.0% and the median time to
      PD was 9.0 months (range 4.6-44.3 months). Overall progression-free survival was
      95.3%, 72.1% and 64.1% after 0.5-, 1- and 2-years. Effects of initial therapy on
      TSEBT treatment response and side effects to TSEBT were also analyzed.
      CONCLUSION: In conclusion, the present study confirms that high-dose TSEBT is an
      effective, but generally not a curative therapy in the management of CTCL. High
      dose treatment yielded significantly better results than low-dose treatment with
      4 Gy. TSEBT offers significant palliation in most patients when other skin
      directed or systemic treatments have failed.

PMID- 21736503
TI  - Leptomeningeal melanomatosis: stabilization of disease due to radiation,
      temozolomide and intrathecal liposomal cytarabine.

PMID- 21736504
TI  - Safety and efficacy of temsirolimus in heavily pretreated patients with
      metastatic renal cell carcinoma.
AB  - BACKGROUND: First line treatment with temsirolimus is considered standard of care
      in poor risk patients with metastatic renal cell carcinoma. The role of
      temsirolimus in pretreated patients with any risk profile is unclear. The aim of
      this retrospective analysis was to investigate the impact of temsirolimus in
      patients who had progressed on various treatment lines. MATERIAL AND METHODS:
      From April 2007 to July 2009, all patients who had progressed on receptor
      tyrosine kinase-inhibitors, VEGF-antibodies and other agents were treated with
      temsirolimus (25 mg weekly). Physical examination, white blood cell count and
      chemistry were obtained weekly and tumor response was assessed every 12 weeks.
      RESULTS: Thirty patients with a median age of 68 years range (44-81) received
      treatment with temsirolimus. Most patients were categorized intermediate risk
      (60%) and the majority had three or more metastatic sites (56.7%). Temsirolimus
      was median the fourth (range 2-5) systemic treatment line. Grade 3 and 4
      toxicities were rare and consisted of anemia, thrombocytopenia and hyperglycemia.
      Objective remission and stable disease were achieved in 13.3% and 60% of the
      patients, respectively. The median progression free survival was 4.9 months (2.93
      6.81 95% CI). CONCLUSION: Temsirolimus appears feasible, safe and active in
      heavily pretreated patients.

PMID- 21736505
TI  - Mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic
      lateral sclerosis.
AB  - BACKGROUND AIMS: Amyotrophic lateral sclerosis (ALS) is a progressive
      neurodegenerative disorder characterized by the loss of brain and spinal cord
      motor neurons (MN). The intraspinal and systemic grafting of mesenchymal stromal
      cells (MSC) was used to treat symptomatic transgenic rats overexpressing human
      superoxide dismutase 1 (SOD1) in order to alleviate the disease course and
      prolong the animals' lifespan. METHODS: At the age of 16 weeks (disease onset)
      the rats received two grafts of MSC expressing green fluorescent protein (GFP(+)
      MSC) on the same day, intraspinally (10(5) cells) and intravenously (2 * 10(6)
      cells). Sham-treated animals were injected with phosphate-buffered saline (PBS).
      Motor activity, grip strength and body weight were tested, followed by
      immunohistochemical analysis. RESULTS: The combined grafting of MSC into
      symptomatic rats had a significant effect on motor activity and grip strength
      starting 4 weeks after transplantation. The lifespan of animals in the treated
      group was 190 +/- 3.33 days compared with 179 +/- 3.6 days in the control group
      of animals. Treated rats had a larger number of MN at the thoracic and lumbar
      levels; these MN were of larger size, and the intensity of terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL)
      staining in the somas of apoptotic MN at the thoracic level was much lower than
      in sham-treated animals. Transplanted GFP(+) MSC survived in the spinal cord
      until the end stage of the disease and migrated both rostrally and caudally from
      the injection site. CONCLUSIONS: Intraspinal and intravenous transplantation of
      MSC has a beneficial and possibly synergistic effect on the lifespan of ALS
      animals.

PMID- 21736506
TI  - Somatic mutation of PHF6 gene in T-cell acute lymphoblatic leukemia, acute
      myelogenous leukemia and hepatocellular carcinoma.
AB  - INTRODUCTION: Somatic mutations in plant homeodomain finger protein 6 (PHF6) gene
      have recently been reported in T-cell acute lymphoblastic leukemia (T-ALL),
      strongly suggesting its role in the pathogenesis of human cancers. MATERIALS AND
      METHODS: To see whether the PHF6 mutation occurs in other malignancies, we
      analyzed entire coding sequences of PHF6 in 231 hematologic malignancies [105
      acute myelogenous leukemias (AML), 66 pre-B-ALL, 23 T-ALL, one undifferentiated
      acute leukemia and 36 multiple myelomas] by single-strand conformation
      polymorphism assay. Also, we analyzed the mutation in 236 solid cancers,
      including 41 lung, 39 hepatocellular (HCC), 36 breast, 40 colorectal, 40 gastric
      and 40 prostate carcinomas. RESULTS: In the hematologic malignancies, there were
      11 PHF6 mutations that were detected not only in T-ALL (34.7%) (five adult and
      three childhood T-ALL), but also in two AML (1.9%) (one acute monocytic leukemia
      and one AML minimally differentiated). In addition, there was a PHF6 mutation in
      the HCC (2.6%). The PHF6 mutations were detected in both male and female
      patients, and consisted of six frameshift, three nonsense and two intron
      mutations. CONCLUSION: Our data suggest that PHF6 mutation might play a role in
      tumorigenesis not only of T-ALL, but also of AML and HCC.

PMID- 21736507
TI  - A randomized double-blind sham-controlled comparison of unilateral and bilateral
      repetitive transcranial magnetic stimulation for treatment-resistant major
      depression.
AB  - OBJECTIVES: High frequency left-sided (HFL) and low frequency right-sided (LFR)
      unilateral repetitive transcranial magnetic stimulation (rTMS) are efficacious in
      treatment-resistant major depression (TRD). Similar benefit has been suggested
      for sequential bilateral rTMS (LFR then HFL). There are few published reports on
      the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS.
      Therefore, this study evaluated the efficacy of HFL and sequential bilateral rTMS
      compared to sham in TRD. METHODS: Subjects between the ages of 18 and 85 were
      recruited from a tertiary care university hospital. Seventy-four subjects with
      TRD and a 17-item Hamilton Depression Rating Scale (HDRS) greater than 21 were
      randomized to receive unilateral, bilateral, or sham rTMS. The rates of remission
      were compared among the three treatment groups. RESULTS: The remission rates
      differed significantly among the three treatment groups using a modified
      intention to treat analysis that excluded subjects who did not respond to
      electroconvulsive therapy (ECT) during the current episode. The remission rate
      was significantly higher in the bilateral group than the sham group. The
      remission rate in the unilateral group did not differ from either group.
      CONCLUSION: These findings warrant larger controlled studies that compare the
      efficacy of sequential bilateral rTMS and HFL rTMS in TRD.

PMID- 21736508
TI  - War and infection in the pre-antibiotic era: the Third Ottoman Army in 1915.
AB  - BACKGROUND: The aim of this study, which evaluated historical data, was to
      delineate the probable impacts of infectious diseases on human populations under
      extraordinary circumstances. The second goal was to disclose the mortality rates
      for infectious diseases in the absence of antibiotics. METHODS: The Third Ottoman
      Army records at the Turkish General Staff Military History and Strategic Study
      Directorate were studied retrospectively for the period between March 1915 and
      February 1916. RESULTS: For the Third Ottoman Army, the number of infection
      related deaths over the single-year period was 23,601. Malaria, relapsing fever
      and dysentery were the most common infections. In that pre-antibiotic era, the
      highest mortality rates were seen for cholera (80%), pulmonary tuberculosis (58%)
      and typhoid fever (51%). However, typhus had the maximum share in soldier deaths
      (6053 soldiers). The rate of vector-borne infections peaked in the summer of
      1915, while the frequency of respiratory tract infections was highest in the
      colder months. In contrast, gastrointestinal tract infections appeared to
      maintain a steady state throughout the year. CONCLUSIONS: If the wartime data for
      1915 are accepted to provide a model for extraordinary circumstances in the 21st
      century, vector-borne, respiratory tract and gastrointestinal infections can be
      accepted as the challenging issues with significant mortality.

PMID- 21736509
TI  - Long-term carriage of extended-spectrum beta-lactamase-producing Escherichia
      coli.
AB  - In 2009 we described an outbreak caused by extended-spectrum beta-lactamase
      (ESBL)-producing Escherichia coli in southern Sweden that occurred during 2005
      2006. An important finding from the investigation was the long carriage times of
      the ESBL-producing E. coli in several of the patients, which in some cases
      exceeded 30 months. Here we report findings from the continued follow-up of
      bacterial carriage. In September 2010, 5 of the 42 patients still carried the
      bacteria after a median of 58 months (range 41-59 months), 18 had had repeatedly
      negative cultures after shedding bacteria for a median of 7.5 months (range 0-39
      months), 16 had died while still shedding the bacteria for a median of 9 months
      (range 0-38 months), and 3 had been lost to follow-up.

PMID- 21736510
TI  - Oropharyngeal tularemia in father and son after consumption of under-cooked
      rabbit meat.
AB  - Tularemia has been recognized for more than 10 y in Serbia, since the first
      epidemic of tularemia occurred in Sokobanja region in 1999. We report 2 cases of
      oropharyngeal tularemia in a father and son after the consumption of under-cooked
      rabbit meat. Both presented with fever, unilateral tonsillopharyngitis and
      cervical lymphadenitis.

PMID- 21736511
TI  - Clinical characteristics of acute hepatitis A complicated by acute kidney injury.
AB  - BACKGROUND: The incidence of acute viral hepatitis A (AHA) in Korea is increasing
      rapidly. Additionally, we are encountering more cases with acute kidney injury
      (AKI), which was once regarded as a rare complication of AHA. Thus, we
      investigated recent aspects of the incidence and clinical characteristics of AHA
      complicated by AKI. METHODS: Patients diagnosed with AHA at 2 referral hospitals
      in Seoul during the period January 2006 to December 2009 were enrolled. RESULTS:
      Of 1025 patients, 71 (6.9%) had AKI. The incidence of AKI was 3.1% in 2006, 6.0%
      in 2007, 8.9% in 2008, and 6.9% in 2009. Patients with AKI were predominantly
      male, heavy alcohol drinkers, and smokers, and also had a higher rate of
      underlying hypertension than patients without AKI. At admission, patients with
      AKI had significantly higher white blood cell counts, prolonged prothrombin
      times, and elevated liver enzymes, including total and direct bilirubin, gamma
      glutamyltransferase, and C-reactive protein. Additionally, patients with AKI had
      a higher peak total bilirubin level and lower initial serum albumin level than
      patients without AKI. CONCLUSION: Although most patients with AHA complicated by
      AKI recover with conservative treatment, we should pay particular attention to
      patients who have risk factors for AKI.

PMID- 21736512
TI  - Spontaneously draining acute otitis media in children: an observational study of
      clinical findings, microbiology and clinical course.
AB  - OBJECTIVES: To study the outcome of acute otitis media (AOM) with otorrhoea in
      children managed initially without antibiotics, in relation to bacterial and
      clinical findings, and to identify those who may benefit from antibiotics.
      METHODS: Otherwise healthy, not otitis prone children aged 2-16 y, presenting
      with AOM with spontaneous otorrhoea, were recruited from primary care and
      followed at selected ear, nose and throat (ENT) clinics. Specimens for bacterial
      investigations were obtained; symptoms were registered on a daily basis. The main
      outcomes measured were the frequency of children treated with antibiotics due to
      persisting AOM within 9 days in relation to clinical and bacteriological
      findings, and new AOM within 3 months. RESULTS: Twelve of 71 children who
      completed the trial received antibiotics during the first 9 days due to lack of
      improvement. One received antibiotics after 16 days due to relapsing AOM and 6
      received antibiotics after 30 days due to new AOM. At 2-4 days following
      inclusion, over 70% of children showed normalized eardrum status and markedly
      reduced secretion. Alloiococcus otitidis was found in 23 samples, Streptococcus
      pneumoniae in 12, Streptococcus pyogenes in 6, and Fusobacterium nucleatum in 5.
      Mycoplasma pneumoniae, Chlamydia pneumoniae, and Fusobacterium necrophorum were
      not detected. Antibiotics were prescribed more extensively to children with a
      pulsating eardrum and abundant purulent secretion. All children with S. pyogenes
      received antibiotics, whereas children with only A. otitidis did not.
      CONCLUSIONS: The results suggest that antibiotics are indicated in AOM with
      otorrhoea and the presence of abundant purulent secretion, a pulsating eardrum,
      or the presence of S. pyogenes. The presence of only A. otitidis was not
      associated with a more prolonged course or the need for antibiotics.

PMID- 21736513
TI  - Association of dental anxiety to personality traits in a general population
      sample of Finnish University students.
AB  - OBJECTIVE: To estimate the association between personality and dental anxiety
      among Finnish University students. MATERIALS AND METHODS: A total of 880
      university students in Finland returned the questionnaires addressing dental
      anxiety by using the Modified Dental Anxiety Scale (MDAS) questionnaire. In
      addition, the personality of traits (neuroticism, extraversion, agreeableness,
      conscientiousness and openness to experience) were noted. Personality traits of
      students were compared with the level (high, mild or none) of dental anxiety
      derived from the MDAS questionnaire. The relative odds of dental anxiety
      associated with the level of dental anxiety were estimated by logistic
      regression, Chi-Square tests and one-way analysis of variance (ANOVA). RESULTS:
      Median age of the respondents was 22 years. Of the respondents, 99 (11.3%) were
      classified as dentally anxious patients (90, 12.2% of females; 9, 6.6% of
      males)). Neuroticism was the only personality trait that was significantly
      associated with dental fear (p < 0.001). A tendency, although not significant,
      was seen between high dental fear and lower extraversion and agreeableness.
      CONCLUSIONS: Of the five different personality traits, neuroticism was a
      significant risk factor for developing dental anxiety, and this should be
      recognized in clinical practice.

PMID- 21736514
TI  - Neuropsychological safety of nucleus accumbens deep brain stimulation for major
      depression: effects of 12-month stimulation.
AB  - OBJECTIVES: Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) has
      antidepressant effects in patients suffering from treatment-resistant depression
      (TRD). However, limited information exists regarding the impact of NAcc-DBS on
      cognitive functioning. The aim of this study was to examine whether NAcc-DBS in
      patients with TRD has any cognitive effects. METHODS: A comprehensive
      neuropsychological battery was administered to 10 patients with TRD before onset
      of bilateral NAcc-DBS and after 1 year of DBS stimulation. Neuropsychological
      testing covered the domains of attention, learning and memory, executive
      functions, visual perception, and language. Performance was analyzed at baseline
      and after 1 year of continuous DBS. RESULTS: No evidence was found for cognitive
      decline following NAcc-DBS comparing test results after 1 year of NAcc-DBS with
      baseline. However, significantly improved cognitive performance on tests of
      attention, learning and memory, executive functions and visual perception was
      found. In addition, there was a general trend towards cognitive enhancement from
      below average to average performance. These procognitive effects were independent
      of the antidepressant effects of NAcc-DBS or changes in NAcc-DBS parameters.
      CONCLUSIONS: These results not only support cognitive safety of NAcc-DBS but also
      stress its beneficial role in augmenting cognitive performance in patients with
      TRD.

PMID- 21736515
TI  - Voluntary exercise does not ameliorate context memory and hyperarousal in a mouse
      model for post-traumatic stress disorder (PTSD).
AB  - OBJECTIVES: We investigated the effects of voluntary wheel running as model for
      intervention on the development of contextual fear and hyperarousal in a mouse
      model of post-traumatic stress disorder (PTSD). Physical exercise in general has
      been associated with improved hippocampus-dependent memory performance both in
      animals and humans. However, studies that have tried to link physical exercise
      and contextual conditioning in an animal model of PTSD, revealed mixed findings.
      METHODS: Here we tested contextual fear conditioning, generalized fear response,
      acoustic startle response and emotionality in C57BL/6NCrl mice which had free
      access to a running wheel for 28 days, compared with control animals which did
      not run and mice which did not receive a shock during the conditioning phase.
      RESULTS: We found no significant effects of voluntary running on the above
      mentioned variables, except for enhanced anxiety levels in the Dark-Light-Box and
      O-Maze tests of running mice. CONCLUSIONS: Our results suggest that running as a
      model for intervention does not ameliorate contextual aversive learning but has
      the potency to change emotional behaviours.

PMID- 21736516
TI  - Microangiopathy of the inner ear, deafness, and cochlear implantation in a
      patient with Susac syndrome.
AB  - CONCLUSION: The cochlear implant was beneficial as an attempt to restore hearing
      and improve communication abilities in this patient with profound sensorineural
      hearing loss secondary to Susac syndrome. OBJECTIVE: To report the audiological
      outcomes of cochlear implantation (CI) in a young woman with Susac syndrome after
      a 6-month follow-up period. Susac syndrome is a rare disorder. It is clinically
      characterized by a typical triad of sensorineural deafness, encephalopathy, and
      visual defect, due to microangiopathy involving the brain, inner ear, and retina.
      METHODS: This was a retrospective review of a case at a tertiary referral center.
      After diagnosis, the patient was evaluated by a multidisciplinary team and
      received a cochlear implant in her right ear. RESULTS: The patient achieved 100%
      open-set sentence recognition in noise conditions and 92% monosyllable and 68%
      medial consonant recognition in quiet conditions after 6 months of implant use.
      She reported the use of the telephone 3 months after activation.

PMID- 21736517
TI  - Sector wide approaches for health in small island states: lessons learned from
      the Solomon Islands.
AB  - Sector Wide Approaches (SWAps) have increasingly been implemented in countries
      around the world as a mechanism for effective delivery of health sector funding
      from various sources. Despite the global focus on aid effectiveness, SWAps have
      been under-examined. In 2007, the Solomon Islands and development partners began
      discussing a health SWAp making the Solomon Islands one of the first fragile
      states globally to adopt a SWAp. This paper explores the establishment and
      implementation of a health SWAp in the Solomon Islands as a specific case study
      with lessons learned for the region as well as for aid architecture in fragile
      states more generally. Tensions between donors and the government impeded
      agreement and early implementation and country ownership of the SWAp idea was
      muted. Since mid-2009, however, the Solomon Islands SWAp has made strong progress
      with greater government ownership and with more focus on partnership and
      harmonisation rather than on funding mechanisms. The SWAp mechanism has been a
      challenge for the capacity-constrained Solomon Islands health sector and for
      development partners familiar with other aid modalities, but current momentum
      suggests that the SWAp will have a positive impact on adherence to agreed aid
      effectiveness principles.

PMID- 21736518
TI  - Encapsulation of hydrophobic aroma in whey protein nanoparticles.
AB  - Aroma-loaded nanoparticles (d < 300 nm) were prepared by cross-linking denatured
      whey protein through pH-cycling. The effect of nanoparticulation conditions and
      aroma concentration on the physicochemical characteristics of nanoparticles and
      aroma release profile was studied. Better retention of aroma was observed when
      ethyl hexanoate was added before nanoparticle formation. The highest aroma
      retention was obtained for nanoparticles produced at pH 5.0 and 5.5 without
      calcium addition. These nanoparticles are characterized by a less compact and
      more porous internal structure allowing a higher loading of aroma. Increasing
      aroma concentration increased the diameter and the voluminosity of the aroma
      loaded nanoparticles. The percentage of aroma retention showed an increase from
      7% to 24% over the tested concentration range while the value averaged 2% for
      native or denatured whey protein. Encapsulation of ethyl hexanoate in whey
      protein nanoparticles reduced the mass transfer of aroma at the surface of the
      matrix and improved its retention.

PMID- 21736519
TI  - Phase-separated chitosan-fibrin microbeads for cell delivery.
AB  - Matrix-enhanced delivery of cells is a promising approach to improving current
      cell therapies. Our objective was to create cell-laden composite microbeads that
      combine the attractive features of the natural polymers chitosan and fibrin.
      Liquid polydimethylsiloxane was used to emulsify a chitosan-fibrinogen solution
      containing suspended human fibroblast cells, followed by initiation of thrombin
      mediated polymerization of fibrin and thermal/pH-mediated gelation of chitosan.
      Chitosan/fibrin weight percent (wt%) ratios of 100/0, 75/25, 50/50 and 25/75 were
      investigated. Microbead diameters ranged from 275 +/- 99 um to 38 +/- 10 um using
      impeller speeds from 600 to 1400 rpm. Fibroblasts remained viable on day 1 post
      fabrication in all matrices, but cell viability was markedly higher in high
      fibrin microbeads by day 8 post-fabrication. Cell spreading and interaction with
      the extracellular matrix was also markedly increased in high-fibrin matrices.
      Such composite microbeads containing viable entrapped cells have potential for
      minimally invasive delivery of cells for a variety of tissue repair applications.

PMID- 21736520
TI  - Influence of alginate cross-linking method on neurite response to
      microencapsulated neurotrophin-producing fibroblasts.
AB  - Transplantation of cells genetically modified to produce neurotrophins is a
      promising spinal cord repair strategy. Previously we showed that fibroblasts
      engineered to produce brain-derived neurotrophic factor (Fb/BDNF)
      microencapsulated in alginate survive, continue to grow and express bioactive
      BDNF. We here compared the effects of different alginate crosslinkers on dorsal
      root ganglia (DRG) neurite growth using alginate-encapsulated Fb/BDNF. Aqueous
      sodium alginate (+/-Fb/BDNF) was contacted with different calcium salts, and used
      as substrate for DRG growth. Length, number and orientation of neurites were
      measured. Chloride or carbonate salts promoted significantly more neurite growth
      than sulphate, with or without Fb/BDNF, although encapsulated Fb/BDNF stimulated
      significantly more neurite growth than cell-free. An Fb/BDNF-derived neurotrophin
      concentration gradient directionally guided DRG neurite growth. This positive
      effect of alginate-encapsulated Fb/BDNF on neurite growth/guidance shows promise
      for enhanced regeneration and guidance of axons towards a specific target in the
      injured spinal cord.

PMID- 21736521
TI  - Formulation, pharmacokinetics and biodistribution of Ofloxacin-loaded albumin
      microparticles and nanoparticles.
AB  - Albumin microparticles containing Ofloxacin (Fluoroquinolone derivative commonly
      used in hospitals) were formulated by the spray dry method. By decreasing the
      pump feed rate or the total polymer concentration, a mixture of
      albumin/hypromellose acetate succinate (HPMCAS) microparticles and nanoparticles
      (MP/NP), containing Ofloxacin, were formulated. MP/NP were characterized, in
      vitro (particle size, zeta potential, and encapsulation efficiency). A comparison
      of the pharmacokinetics and biodistribution of aqueous Ofloxacin and Ofloxacin
      loaded MP/NP, in Balb/c mice, revealed that peak concentrations were reduced in
      the serum, liver, spleen and brain, and a more sustained release was observed in
      serum and all of the organs tested for Ofloxacin MP/NP, compared to aqueous
      Ofloxacin. The MP/NP formulation allowed extended release by 24 h in the liver
      and more than 48 h in the brain. In serum, the elimination rate of Ofloxacin
      MP/NP is slower, the half life is longer, area under the plasma concentration
      time curve is decreased and volume of distribution is increased.

PMID- 21736522
TI  - Enzyme immobilisation in permselective microcapsules.
AB  - The objective of this investigation was to study the permselective behaviour of
      calcium alginate membranes, including the modifying effects of silica additives,
      which were subsequently used as microcapsule shells. Diffusion experiments and
      HPLC were carried out to ascertain the size-exclusion property of the membranes
      for a mixed molecular-weight dextran solution. Hollow microcapsules containing
      the enzyme dextranase were prepared using double concentric nozzles and the
      encapsulation performance was evaluated based on an analysis of the enzyme
      reactivity and stability. To improve mass transport within the microcapsules,
      magnetic nanoparticles were introduced into the liquid core and agitated using an
      alternating external magnetic field. The modified membranes exhibited better size
      exclusion behaviour than the unmodified membranes. The magnetic nanoparticles
      slightly improved mass transport inside the microcapsule. The encapsulated enzyme
      yielded nearly 80% of the free enzyme activity and retained about 80% of the
      initial catalytic activity even after being used for eight reaction cycles.

PMID- 21736523
TI  - Poly(N-vinylcaprolactam-co-methacrylic acid) hydrogel microparticles for oral
      insulin delivery.
AB  - pH-sensitive copolymeric hydrogels prepared from N-vinylcaprolactam and
      methacrylic acid monomers by free radical polymerization offered 52%
      encapsulation efficiency and evaluated for oral delivery of human insulin. The in
      vitro experiments performed on insulin-loaded microparticles in pH 1.2 media
      (stomach condition) demonstrated no release of insulin in the first 2 h, but
      almost 100% insulin was released in pH 7.4 media (intestinal condition) in 6 h.
      The carrier was characterized by Fourier transform infrared, differential
      scanning calorimeter, thermogravimetry and nuclear magnetic resonance techniques
      to confirm the formation of copolymer, while scanning electron microscopy was
      used to assess the morphology of hydrogel microparticles. The in vivo experiments
      on alloxan-induced diabetic rats showed the biological inhibition up to 50% and
      glucose tolerance tests exhibited 44% inhibition. The formulations of this study
      are the promising carriers for oral delivery of insulin.

PMID- 21736524
TI  - A preliminary study on the morphological and release properties of hydroxyapatite
      alendronate composite materials.
AB  - Inhibition of osteoclasts by bisphosphonate is one strategy to be explored in
      order to avoid a revision surgery. The purpose of this preliminary work is to
      synthesize hydroxyapatite-alendronate (HA-ALN) composites as carrier for ALN that
      could improve its site specific activity. HA-ALN composites were prepared by the
      co-precipitation method. Process parameters such as HA:ALN w/w ratio (1:1, 5:1
      and 10:1) and HA incubation times (6, 24, 48 and 72 h) were evaluated.
      Morphological, physical-chemical characterization and biocompatibility tests were
      performed. TEM and SEM analyses confirmed ALN precipitation as fine network onto
      HA. The results of physical-chemical characterization confirmed the presence of
      ALN in the composites and its interaction with HA. ALN content resulted between
      60% and 80% in the HA:ALN 5:1 and 10:1 ratios composites. ALN release reached 80%
      from HA-ALN 10:1 composites. Biological tests revealed that complexation with HA
      increased ALN biocompatibility by three times. These preliminary results
      demonstrated that HA-ALN composites could be considered a carrier to control ALN
      release.

PMID- 21736525
TI  - Preparation of biodegradable nanoparticles of tri-block PLA-PEG-PLA copolymer and
      determination of factors controlling the particle size using artificial neural
      network.
AB  - The purpose of this study was to prepare nanoparticles made of tri-block
      poly(lactide)-poly(ethylene glycol)-poly (lactide) (PLA-PEG-PLA) with controlled
      size as drug carrier. Artificial neural networks (ANNs) were used to identify
      factors which influence particle size. In this way, PLA-PEG-PLA was synthesized
      and was made into nanoparticles by nanoprecipitation under different conditions.
      The copolymer and the resulting nanoparticles were characterized by various
      techniques such as proton nuclear magnetic resonance spectroscopy, Fourier
      transform infrared spectroscopy, gel permeation chromatography, photon
      correlation spectroscopy and scanning electron microscopy. The developed model
      was assessed and found to be of high quality. The model was then used to survey
      the effects of processing factors including polymer concentration, amount of
      drug, solvent ratio and mixing rate on particle size of polymeric nanoparticles.
      It was observed that polymer concentration is the most affecting parameter on
      nanoparticle size distribution. The results demonstrate the potential of ANNs in
      modelling and identification of critical parameters effective on final particle
      size.

PMID- 21736526
TI  - Paclitaxel-loaded polyester nanoparticles prepared by spray-drying technology: in
      vitro bioactivity evaluation.
AB  - Paclitaxel (PTX), an antimicrotubular agent used in the treatment of ovarian and
      breast cancer, was encapsulated in nanoparticles (NPs) of poly(lactide-co
      glycolide) (PLGA) and poly(epsilon-caprolactone) (PCL) polymers using the spray
      drying technique. Morphology, size distribution, drug encapsulation efficiency,
      thermal degradation and drug release were characterized. MCF7 cells were employed
      to evaluate the efficacy of the systems on cell cycle and cytotoxicity. The
      particle size was in the range 0.8-1 um. The incorporation efficiency of PTX was
      more than 80% in all NPs obtained. In vitro drug release took place during 35
      days, and drug release rates were in the order PCL > PLGA 50:50 > PLGA 75:25.
      Unloaded NPs showed to be cytocompatible at MCF7 cells. PTX-loaded NPs
      demonstrated the release of the drug block cells in the G2/M phase. All PTX
      loaded formulations showed their efficacy in killing MCF7 cells, mainly PTX
      loaded PLGA 50:50 and PLGA 75:25 that cause a decrease in cell viability lower
      than 20%.

PMID- 21736527
TI  - Insulin-loaded PLGA microparticles: flow focusing versus double emulsion/solvent
      evaporation.
AB  - CONTEXT: Oral administration of insulin is severely limited by very low
      bioavailability. Biocompatible polymeric nanocarriers have been investigated to
      overcome this problem. Flow focusing (FF) has revolutionized current engineering
      of poly(D,L-lactide-co-glycolide) (PLGA) based micromedicines. This technique has
      never been used to formulate insulin-loaded PLGA microparticles. OBJECTIVE:
      Investigation of the benefits rising from the synthesis of insulin-loaded PLGA
      microplatforms by FF, compared to double emulsion/solvent evaporation method.
      MATERIALS AND METHODS: Both synthesis methodologies were compared in terms of
      geometry, surface physicochemical properties and insulin vehiculization
      capabilities. The stability of the peptide during the formulation procedure was
      further analysed. RESULTS: FF permitted the preparation of insulin-loaded
      microcarriers with better geometry and physicochemical properties for the oral
      route, along with greater insulin loading capabilities and sustained insulin
      release kinetics. DISCUSSION AND CONCLUSION: Results have lead to the
      identification of the best formulation conditions for the engineering of insulin
      loaded PLGA microparticles against diabetes.

PMID- 21736528
TI  - Percutaneous toxicity of dinitrochlorobenzene (DNCB) in rats.
AB  - Contact hypersensitivity reaction (CHS) is a T-cell-mediated skin inflammatory
      reaction to cutaneous exposure to small sensitizing chemicals, haptens. While the
      significance of local inflammatory skin response to the hapten application in CHS
      induction and expression is known, there is paucity of data concerning systemic
      inflammation in CHS. In this study, changes in cellular (peripheral blood
      granulocytes) and humoral (plasma tumor necrosis factor (TNF)-alpha levels)
      components of inflammation during sensitization of rats with two consecutive
      applications of dinitrochlorobenzene (DNCB) were examined. The impact of
      sensitization on these parameters was determined by employing low (0.4%) and high
      (4%) hapten doses and by examining the dynamics (i.e. one and three days
      following the last application of DNCB) of these changes. Dose-dependent increase
      in relative numbers and priming (for respiratory burst and adhesion) effect of
      skin sensitization with DNCB on peripheral blood neutrophils in rats were noted.
      No changes in circulating TNF-alpha levels were observed following the
      sensitization. The increase in lung myeloperoxidase content and histologically
      evident presence of neutrophils was observed in lungs of the sensitized rats. The
      changes in granulocyte priming for adhesion might have accounted for the observed
      increase in lung neutrophil content in the sensitized rats.

PMID- 21736529
TI  - Fenofibrate plus simvastatin (fixed-dose combination) for the treatment of
      dyslipidaemia.
AB  - INTRODUCTION: Statin use results in a significant reduction of cardiovascular
      disease (CVD) risk. However, patients still have residual CVD risk, even if they
      are receiving optimal statin treatment. AREAS COVERED: This review, based on a
      Pubmed/Scopus search, discusses the available evidence regarding the use of a
      fixed-dose fenofibrate plus simvastatin combination. This combination is useful
      for patients with mixed dyslipidaemia because it improves the overall lipoprotein
      profile. Although in clinical trials the rate of adverse events was not
      significantly greater than monotherapy, patients who receive combination
      treatment should be monitored carefully. Furthermore, in the Action to Control
      Cardiovascular Risk in Diabetes (ACCORD) Study, this combination did not result
      in a significant reduction of CVD events compared with simvastatin monotherapy.
      However, a possible benefit in this trial was observed in the subgroup of
      patients with high triglyceride and low high-density lipoprotein cholesterol
      levels. EXPERT OPINION: The fixed-dose fenofibrate plus simvastatin combination
      treatment produces additive results and is safe when patients are properly
      monitored. Existing evidence appears to support the addition of fenofibrate to
      simvastatin treatment for the reduction of residual CVD risk in patients with
      atherogenic dyslipidaemia. However, this combination did not lead to better
      clinical outcomes in the absence of dyslipidaemia.

PMID- 21736530
TI  - A pharmacoeconomic analysis of severe psoriasis therapy: a review of treatment
      choices and cost efficiency.
AB  - INTRODUCTION: Psoriasis is a chronic, inflammatory disease afflicting 2% of the
      US population; it results in significant morbidity. The annual healthcare costs
      related to psoriasis are an estimated $11.3 billion and, with an expanding
      biologic market, an updated costs analysis is needed. AREAS COVERED: Current
      treatments, including systemic agents (acitretin, cyclosporine, methotrexate),
      phototherapies and all available biologics (adalimumab, etanercept, infliximab,
      alefacept, ustekinumab) appropriate for severe psoriasis are described
      mechanistically and with regard to their efficacy, quality-of-life improvements
      and side effects. A cost-efficacy model considering US health-system-based annual
      costs, clinical and quality-of-life improvements was created. Reported Psoriasis
      Area and Severity Index improvement of 75% from baseline (PASI-75) scores,
      Dermatology Life Quality Index (DLQI) improvements and estimated costs of
      medications are described. Annual costs ranged from $1330 for methotrexate to
      $48,731 for high-dose etanercept. The lowest cost per achieving DLQI minimally
      important difference was from phototherapy; the highest was from alefacept. The
      lowest costs per patient achieving PASI-75 was from methotrexate and the highest
      was from alefacept. EXPERT OPINION: Phototherapies and methotrexate offer high
      efficacy for their costs. Therapeutic approaches must be individualized for each
      patient given all considerations described.

PMID- 21736531
TI  - Long-term follow-up of a randomized controlled trial of observation versus
      surgery for acute cholecystitis: non-operative management is an option in some
      patients.
AB  - BACKGROUND: Cholecystectomy is routinely recommended to prevent recurrent disease
      after an initial episode of acute cholecystitis. Therefore, randomized controlled
      trials have mainly focused on the timing of surgery, but many patients scheduled
      for cholecystectomy have deferred surgery with long periods of symptom-free
      intervals. Our present aim is to examine the long-term feasibility and safety of
      observation compared with surgery. METHODS: Trial of 64 patients with acute
      cholecystitis previously randomized to observation or cholecystectomy, which
      examined outcome in terms of completed randomized treatment and appearance of
      further symptoms and the need for surgical treatment. Thirty-three patients were
      randomized to observation and 31 patients to cholecystectomy. Median follow-up
      was 14 years. RESULTS: Of the 33 patients randomized to observation, 11 (33%)
      experienced a new event of gallstone-related disease (eight (24.2%) had acute
      cholecystitis) and 11 (33%) were operated. No significant difference (p = 0.565)
      was found between the two randomized groups with regard to recurrent disease or
      complications. Virtually no surgery took place after 5 years of follow-up. The
      difference in completed randomized treatment between the groups was not
      significant (p = 0.077). Long-term mortality was equal in those operated and in
      those observed. CONCLUSIONS: Twenty-four percent of the patients experienced
      recurrent cholecystitis, but escalation of disease severity or increased
      mortality was not observed. Long-term observation after acute cholecystitis was
      feasible in two-thirds of the patients as the risk for recurrent disease was
      negligible after 5 years.

PMID- 21736532
TI  - Helicobacter pylori cagA polymorphism and gastric inflammation: an international
      comparison between Japanese and Brazilian patients.
AB  - OBJECTIVE: Gastritis induced by Helicobacter pylori can cause the onset of
      gastric cancer, and H. pylori cytotoxin associated gene A (cagA) is considered to
      be an important factor for its development. We investigated the relationship
      between the grades of gastritis and cagA phenotype in Japanese and Brazilian
      patients. MATERIAL AND METHODS: We studied 47 Brazilian and 47 age-, gender
      matched Japanese patients. Status of H. pylori infection, the degree of
      histologic gastritis, and the levels of serum pepsinogen levels were evaluated.
      DNA was extracted from paraffin-embedded sections and a portion of the cagA gene
      was amplified using the polymerase chain reaction, followed by direct sequencing
      of the fragment. We investigated the cagA subtype using a newly developed
      restriction fragment length polymorphism (RFLP) system. RESULTS: In H. pylori
      positive patients, the grades of histological and serological gastritis were more
      prominent in the Japanese subjects than their Brazilian counterparts, although no
      difference was detected in the H. pylori-negative subjects. According to cagA
      phenotype analysis, our RFLP system was helpful for evaluating cagA phenotype,
      and we found that the prevalence of the East Asia subtype was significantly
      higher in the Japanese subjects than in the Brazilian. CONCLUSION: Infection with
      H. pylori possessing the East Asian cagA gene contributes to the progression of
      gastritis.

PMID- 21736533
TI  - Targeting Fas/FasL signaling, a new strategy for maintaining bone health.
AB  - The treatment of osteoporosis has been a critical issue in today's medical
      situation. Various therapeutic agents and strategies have been investigated and
      applied, and have proven successful in the treatment of osteoporosis. However,
      some concerns still remain, such as the adverse effects of such treatments. From
      this point of view, a search for novel therapeutic targets, such as Fas
      signaling, remains important.

PMID- 21736534
TI  - Genetic polymorphisms of cytochrome P450 enzymes and antidepressant metabolism.
AB  - INTRODUCTION: The cytochrome P450 (CYP) enzymes are the major enzymes responsible
      for Phase I reactions in the metabolism of several substances, including
      antidepressant medications. Thus, it has been hypothesized that variants in the
      CYP network may influence antidepressant efficacy and safety. Nonetheless, data
      on this field are still contradictory. The authors aim to give an overview of the
      published studies analyzing the influence of CYP highly polymorphic loci on
      antidepressant treatment in order to translate the acquired knowledge to a
      clinical level. AREAS COVERED: The authors collected and compared experimental
      works and reviews published from the 1980s to the present and included in the
      Medline database. The included studies pertain to the effects of CYP gene
      polymorphisms on antidepressant pharmacokinetic parameters and clinical outcomes
      (response and drug-related adverse effects), with a focus on applications in
      clinical practice. The authors focused mainly on in vivo studies in humans
      (patients or healthy volunteers). EXPERT OPINION: Great variability in
      antidepressant metabolism among individuals has been demonstrated. Thus, with the
      current interest in individualized medicine, several genetic tests to detect CYP
      variants have been produced. They provide a potentially useful way to anticipate
      some clinical outcomes of antidepressant treatment, although they will only be
      extensively used in clinical practice if precise and specific treatment options
      and guidelines based on genetic tests can be provided.

PMID- 21736535
TI  - Anticomplement activity of organic solvent extracts from Korea local Amarantaceae
      spp.
AB  - The study evaluated the anticomplement activity from various solvent extracts of
      nine Amarantaceae plants (Achyranthes japonica (Miq.) Nakai, Amaranthus
      mangostanus L., Amaranthus retroflexus L., Amaranthus spinosus L., Celosia
      argentea var. spicata., Amaranthus lividus L., Celosia cristata L., Amaranthus
      viridis L., Gomphrena globosa L.) from South Korea on the classical pathway. We
      have evaluated various organic solvent extract from nine Amarantaceae plants with
      regard to its anticomplement activity on the classical pathway. Achyranthes
      japonica chloroform extracts showed inhibitory activity against complement system
      with 50% inhibitory concentrations (IC(50)) value of 73.1MUg/ml. This is the
      first report of anticomplement activity from Amarantaceae plants.

PMID- 21736536
TI  - The therapeutic potential of PhiC31 integrase as a gene therapy system.
AB  - INTRODUCTION: The phiC31 integrase system is a phage-derived system that offers
      the ability to integrate plasmid DNA into the chromosomes at a subset of
      endogenous preferred locations associated with robust gene expression. Recent
      progress highlights the unique advantages of this system for in vivo gene therapy
      and for use in stem cells. AREAS COVERED: The phiC31 integrase system has been
      under development for ten years and has been demonstrated to be effective for
      integration of plasmids in a variety of tissues and organs for gene therapy in
      animal systems, as well as in isolated human cells. We focus on work with the
      phiC31 integrase system during the past 12-18 months. This work has centered on a
      series of papers involving in vivo delivery of the integrase system to the liver
      and a variety of studies demonstrating the utility of the integrase system in
      stem cells. EXPERT OPINION: We conclude that the phiC31 integrase system has
      significant potential for liver gene therapy, if effective DNA delivery methods
      for large mammals become available. The phiC31 integrase system displays an
      outstanding fit for use in pluripotent stem cells, and this area is expected to
      be the subject of intense development.

PMID- 21736537
TI  - Ornithine transcarbamylase deficiency diagnosed in pregnancy.
AB  - Urea cycle enzymes deficiencies are rare metabolic disorders. Ornithine
      transcarbamylase (OTC) deficiency is the most common type. The syndrome results
      from a deficiency of the mitochondrial enzyme OTC which catalyses the conversion
      of ornithine and carbamoyl phosphate to citrulline. It shows X-linked inheritance
      and typically remains asymptomatic until late infancy or early childhood. The
      severity of the symptoms depends on the age of the patient and the duration of
      hyperammonemia. Female heterozygotes are more difficult to diagnose. They suffer
      from hyperammonemic periods which can be triggered by trauma, infections,
      surgery, childbirth, parenteral nutrition, and by the initiation of sodium
      valproate therapy. The prognosis of OTC deficiency is better for those with an
      onset after infancy, but morbidity from brain damage does not appear to be linked
      to the number of episodes of hyperammonemia that have occurred. However, early
      diagnosis and prompt initiation of ammonia-lowering treatment are essential for
      survival of these patients. This case presents a patient who was diagnosed with
      OTC deficiency following mental confusion during pregnancy.

PMID- 21736538
TI  - Effects of menopause on hepatic 11beta-hydroxysteroid dehydrogenase type 1
      activity and adrenal sensitivity to adrenocorticotropin in healthy non-obese
      women.
AB  - Menopause is associated with central obesity, dyslipidemia, hypertension and
      insulin resistance, which are also shown in the patients with excess of
      glucocorticoids. However, the interaction of hypothalamic-pituitary-adrenal (HPA)
      axis activity and menopause has not been fully understood. In this study, 55
      healthy non-obese women were recruited, and then divided into two groups,
      premenopausal group (n = 24) and postmenopausal group (n = 31). HPA axis function
      was evaluated by using dexamethasone suppression test (DST; 0.25 mg), and
      adrenocorticotrophic hormone (ACTH)-stimulation test. Moreover, 25 mg cortisone
      acetate test was applied to evaluate the hepatic 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) activity. We found that hepatic 11beta-HSD1
      activity and adrenal response to ACTH were increased in the postmenopausal group
      compared with the premenopausal group, whereas the negative feedback effect of
      dexamethasone did not show significant difference between pre- and postmenopausal
      women. These findings suggest that the adrenal sensitivity to ACTH and hepatic
      11beta-HSD1 activity are increased. The increased cortisol conversion and/or
      synthesis may be contributed to the dysmetabolic features in the postmenopausal
      women.

PMID- 21736539
TI  - A colorimetric, metabolic dye reduction assay detects highly activated platelets:
      application in the diagnosis of heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is caused by antibodies, elicited in
      response to heparin anticoagulant therapy, which can cause extreme platelet
      activation and result in a highly procoagulant state. Most diagnostic tests for
      HIT antibodies measure in vitro platelet activation by detecting aggregation or
      granule release responses. This study demonstrates that the high level of
      activation by HIT antibodies leads to a rapid breakdown of platelet metabolic
      activity. Resting or mildly activated platelets metabolize tetrazolium-based
      indicator dye to a dark colored product, in proportion to cell concentration and
      dye incubation time. Highly activated, procoagulant platelets resulting from
      incubation with HIT antibodies fail to metabolize dye and remain light in color.
      The loss of ability to metabolically reduce indicator dye provides a colorimetric
      endpoint that can be used in an in vitro washed platelet activation assay to
      detect HIT antibodies. In a prospective evaluation, 145 diagnostic specimens were
      tested concurrently by both the colorimetric, dye reduction assay and the
      clinical laboratory standard, radiolabeled-serotonin release assay ((14)C-SRA).
      Results were in agreement for 96-100% of cases, depending on the chosen
      stringency of assay cut-off values. This study demonstrates that the metabolic
      dye reduction assay is comparable to the (14)C-SRA for HIT diagnosis. In
      addition, this novel assay may have even wider applicability, facilitating
      studies on the physiologic and clinical relevance of highly activated platelet
      populations.

PMID- 21736540
TI  - The principle and the potential approach to ROS-dependent cytotoxicity by non
      pharmaceutical therapies: optimal use of medical gases with antioxidant
      properties.
AB  - Regulation of cellular redox balances is important for the homeostasis of human
      health. Thus, many important human diseases, such as inflammation, diabetes,
      glaucoma, cancers, ischemia and neurodegenerative diseases, have been
      investigated in the field of reactive oxygen species (ROS) and oxidative stress.
      To overcome the harmful effect of oxidative stress and ROS, one can directly
      eliminate them by medical gases such as carbon monoxide (CO), hydrogen sulphide
      (H(2)S), and molecular hydrogen (H(2)), or one can induce ROS-resistant proteins
      and antioxidant enzymes to antagonize oxidative stresses. This article reviews
      the molecular mechanisms how these medical gasses work as antioxidants, and how
      ROS resistant proteins are produced in the physiological context. Targeted
      therapeutic modalities to scavenge or prevent ROS might be applied in the
      prevention and treatment of ROS-related diseases in the near future.

PMID- 21736542
TI  - Jun dimerization protein 2 in oxygen restriction; control of senescence.
AB  - Senescent cells show a series of alterations, including a flat and enlarged
      morphology, increase in nonspecific acidic beta- galactosidase activity,
      chromatin condensation, and changes in gene expression patterns. The onset and
      maintenance of senescence are regulated by two tumor suppressor proteins, p53 and
      Rb, whose expression is controlled by two distinct proteins, p19(Arf) and
      p16(Ink4a), respectively, which are encoded by the cdkn2a locus. Transcription
      factor Jun dimerization protein 2 (JDP2) which binds directly to histones and
      DNA, inhibits the acetylation and methylation of core histones and of
      reconstituted nucleosomes that contain JDP2-recognition DNA sequences. JDP2
      deficient mouse embryonic fibroblasts are known to be resistant to replicative
      senescence. Oxygen induces the expression of the JDP2 gene and JDP2 then inhibits
      the recruitment of polycomb repressive complexes (PRCs1 and 2) to the promoter of
      the gene encoding p16(Ink4a), resulting in the inhibition of methylation of
      lysine 27 of histone H3. These findings suggest that chromatin-remodeling
      factors, including the PRC complex controlled by JDP2, are important players in
      the senescence. The newly defined mechanisms that underlie the action of oxygen
      in the induction of JDP2 and cellular senescence are reviewed.

PMID- 21736543
TI  - Development of microwave antennas for thermal therapy.
AB  - There are several different ways for cancer treatment including operation,
      radiation therapy, chemotherapy, gene therapy, immunotherapy, ablation and
      hyperthermia. Techniques utilizing temperature elevation over the tumor region
      are usually called as thermal therapies. In this paper, we will focus on
      hyperthermia which is one of the promising cancer treatments utilizing the
      difference of thermal sensitivity between the tumor and normal tissue. In
      addition, microwave energy is a heating source used for localized hyperthermia.
      Depending on the position and size of the target tumor, several types of
      antennas, which radiate microwave energy to the target, can be selected. This
      paper describes two types of heating schemes which can be used with microwave
      energy, and provides brief explanations of the basic engineering involved. In
      addition, methods used for evaluations of antenna performance are described.

PMID- 21736544
TI  - Gas bioengineering using hemoglobin-vesicles for versatile clinical applications.
AB  - Blood transfusion systems have greatly benefited human health and welfare.
      Nevertheless, some problems remain: possibility of infection, blood type
      mismatching, immunological response, and a short shelf life that is insufficient
      for stockpiling for emergency situations. Realization of artificial O(2) carriers
      is anticipated to solve such problems. During the long development of hemoglobin
      (Hb)-based O(2) carriers, many side effects of cell-free Hb molecules have
      arisen, and have implied the physiological importance of the cellular structure
      of red blood cells (RBCs). Therefore, Hb-vesicles (HbVs) have been developed as
      artificial red cells that encapsulate a concentrated Hb solution in thin lipid
      bilayer vesicles. This Hb encapsulation can shield various toxic effects of
      molecular Hbs, especially reactions with endogenous NO and CO as vasorelaxation
      factors. Physicochemical analyses have clarified that Hb encapsulation retards
      these gaseous reactions significantly. "Gas Bioengineering" is intended to create
      systems using bioengineering and chemical engineering techniques to facilitate
      the transport of or regulate the concentration of endogenous or exogenous gaseous
      molecules (such as O(2), NO, and CO) that are sometimes vital and sometimes toxic
      to humans. Gas bioengineering using HbVs underscores the potential of HbVs as a
      transfusion alternative and promises its use for other clinical applications that
      remain unattainable using RBC transfusion.

PMID- 21736541
TI  - Walking the oxidative stress tightrope: a perspective from the naked mole-rat,
      the longest-living rodent.
AB  - Reactive oxygen species (ROS), by-products of aerobic metabolism, cause oxidative
      damage to cells and tissue and not surprisingly many theories have arisen to link
      ROS-induced oxidative stress to aging and health. While studies clearly link ROS
      to a plethora of divergent diseases, their role in aging is still debatable.
      Genetic knock-down manipulations of antioxidants alter the levels of accrued
      oxidative damage, however, the resultant effect of increased oxidative stress on
      lifespan are equivocal. Similarly the impact of elevating antioxidant levels
      through transgenic manipulations yield inconsistent effects on longevity.
      Furthermore, comparative data from a wide range of endotherms with disparate
      longevity remain inconclusive. Many long-living species such as birds, bats and
      mole-rats exhibit high-levels of oxidative damage, evident already at young ages.
      Clearly, neither the amount of ROS per se nor the sensitivity in neutralizing ROS
      are as important as whether or not the accrued oxidative stress leads to
      oxidative-damage-linked age-associated diseases. In this review we examine the
      literature on ROS, its relation to disease and the lessons gleaned from a
      comparative approach based upon species with widely divergent responses. We
      specifically focus on the longest lived rodent, the naked mole-rat, which
      maintains good health and provides novel insights into the paradox of maintaining
      both an extended healthspan and lifespan despite high oxidative stress from a
      young age.

PMID- 21736545
TI  - The possible involvement of glycogen synthase kinase-3 (GSK-3) in diabetes,
      cancer and central nervous system diseases.
AB  - Glycogen synthase kinase (GSK-3) is a key enzyme in multiple cell processes.
      Since many pharmacological compounds that have effects on common metabolic
      pathways may have uses in many different diseases, we review here the possible
      involvement of glycogen synthase kinase 3 in diabetes, cancer and CNS diseases.
      Moreover, diabetes has recently been strongly linked to CNS diseases such as
      schizophrenia and bipolar illness. GSK-3 is both directly and indirectly
      inhibited by lithium, a key compound for treatment of bipolar disorder. Several
      antipsychotic drugs also affect the GSK-3 mediated pathways and postmortem study
      of brain in schizophrenia led to reports of alterations of GSK-3 activity or mRNA
      message. However, other reports are contradictory. Development of GSK-3
      inhibitors for CNS diseases is complicated by the importance of GSK-3 in glucose
      metabolism and pancreas function and the possible effect of GSK-3 inhibition to
      be oncogenic. Further development of GSK-3 inhibitors for clinical trials should
      be approached with caution.

PMID- 21736546
TI  - Design of magnetic nanoparticles-assisted drug delivery system.
AB  - Magnetic nanoparticles (MNPs) have been designed for multifaceted applications
      such as contrast agents in magnetic resonance imaging (MRI) diagnosis, drug/gene
      carriers for different kinds of therapeutic agents, tissue repair, hyperthermia,
      immunoassay, and cell separation/sensing. This review highlights synthesis
      methods, stabilizers used for surface coating on MNPs, and target ligands for
      ferrying payloads to an interested disease area. Some of the recent biomedical
      applications of MNPs in the field of drug and DNA targeting delivery are
      extensively reviewed.

PMID- 21736548
TI  - Metallodendrimers and dendrimer nanocomposites.
AB  - Dendrimers are polymeric compounds with highly branched structures and
      functionally tunable peripheral groups. Because of their low polydispersity, high
      degree of molecular uniformity, and precisely controlled structure, dendrimers
      are excellent models for demonstrating a variety of biological activities. With
      the attachment of metals ions and/or metals, metallodendrimers or dendrimer
      nanocomposites, respectively, provide diverse characters for a variety of
      applications. Functionalization with additional moieties, such as targeted
      peptides or chromophores, yields metallodendrimers that can find powerful
      applications and exceed the capabilities of nondendritic molecules or small
      molecule analogs. This review introduces the background of metallodendrimers and
      dendrimer nanocomposites. Biomedical applications of metallodendrimers and
      dendrimer nanocomposites will be discussed, including biomimetic catalysts,
      imaging contrast agents (especially for MRI imaging), or biomedical sensors and
      therapeutic agents.

PMID- 21736547
TI  - Recent progress toward hydrogen medicine: potential of molecular hydrogen for
      preventive and therapeutic applications.
AB  - Persistent oxidative stress is one of the major causes of most lifestyle-related
      diseases, cancer and the aging process. Acute oxidative stress directly causes
      serious damage to tissues. Despite the clinical importance of oxidative damage,
      antioxidants have been of limited therapeutic success. We have proposed that
      molecular hydrogen (H(2)) has potential as a "novel" antioxidant in preventive
      and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H(2) has
      a number of advantages as a potential antioxidant: H(2) rapidly diffuses into
      tissues and cells, and it is mild enough neither to disturb metabolic redox
      reactions nor to affect reactive oxygen species (ROS) that function in cell
      signaling, thereby, there should be little adverse effects of consuming H(2).
      There are several methods to ingest or consume H(2), including inhaling hydrogen
      gas, drinking H(2)-dissolved water (hydrogen water), taking a hydrogen bath,
      injecting H(2)- dissolved saline (hydrogen saline), dropping hydrogen saline onto
      the eye, and increasing the production of intestinal H(2) by bacteria. Since the
      publication of the first H(2) paper in Nature Medicine in 2007, the biological
      effects of H(2) have been confirmed by the publication of more than 38 diseases,
      physiological states and clinical tests in leading biological/medical journals,
      and several groups have started clinical examinations. Moreover, H(2) shows not
      only effects against oxidative stress, but also various anti-inflammatory and
      antiallergic effects. H(2) regulates various gene expressions and protein
      phosphorylations, though the molecular mechanisms underlying the marked effects
      of very small amounts of H(2) remain elusive.

PMID- 21736549
TI  - Exotropia Replaces Esotropia as most Common Form of Strabismus; HIV and CPEO; Zoo
      Papers; EOM Innervation Innovation AND Strabology Report of the 37th Annual
      Meeting of the American Association for Pediatric Ophthalmology and Strabismus.

PMID- 21736550
TI  - Strabometry precision: intra-examiner repeatability and agreement in measuring
      the magnitude of the angle of latent binocular ocular deviations (heterophorias
      or latent strabismus).
AB  - BACKGROUND AND PURPOSE: This study was designed to compare heterophoria
      measurements obtained using the methods: prisms cover test (prism alternate cover
      test), von Graefe technique, Maddox rod test and modified Thorington test. Given
      the different methodological features of these tests, our working hypothesis was
      that these tests would not be interchangeable and repeatability would vary.
      METHODS: Horizontal deviation measurements were made at: far distance (six
      meters) and near distance (40 centimeters) on two occasions in 61 young subjects
      of mean age 19.7 years (range 18 -32 years), with essentially normal eyes and
      vision, who were not familiar with the methods used. Statistical repeatability
      and agreement were determined using the Bland and Altman method. RESULTS:
      Repeatability: No difference between the results of the various heterophoria
      tests was statistically significant. Coefficients of repeatability were always
      best when the tests were conducted at far, the cover test being the most
      repeatable. Agreement: Mean differences between absolute values ranged from 1.7
      prism diopters to 5.1 prism diopters for measurements at far and from 2.1 prism
      diopters to 3.4 prism diopters at near. CONCLUSIONS: The alternating prism cover
      test was the most repeatable test for measuring latent horizontal deviations.
      Among the subjective tests, the modified Thorington test was the most repeatable.
      The low level of agreement observed between the different tests makes their
      interchangeable use in clinical practice not recommended.

PMID- 21736551
TI  - Loss of binocular vision (diplopia) and acute comitant esotropia following
      surgical patch removal after unilateral penetrating keratoplasty for keratoconus;
      management.
AB  - PURPOSE: To report a case of acute comitant esotropia after monocular penetrating
      keratoplasty (PKP). CASE REPORT: We present a 17 year old male patient with
      bilateral keratoconus who underwent penetrating keratoplasty in his right eye. He
      experienced diplopia after removal of the patch from the operated eye due to a
      new comitant esotropia in his left (unoperated) eye. Diplopia was controlled
      using prism glasses and then botulinum toxin injections until a penetrating
      keratoplasty was performed in his left eye and binocular vision and fusion
      returned. CONCLUSION: Acute comitant esotropia may occur after loss of binocular
      vision and fusion due to brief ocular patching in a vulnerable patient. Fusion
      can be preserved with non-surgical methods until it can be permanently restored.

PMID- 21736552
TI  - Transient Reversal of a Face Turn (an Abnormal Head Posture, AHP) due to Manifest
      Latent Nystagmus, after Eye Muscle Strabismus Surgery for the Associated
      Infantile Esotropia.
AB  - Patients with infantile esotropia and manifest latent nystagmus adopt a face turn
      towards the fixing eye as a nystagmus dampening mechanism. The surgical plan
      should aim to correct both the face turn and the strabismus. Reversal of the face
      turn after surgery for the strabismus can be (i.e. was) distressing for both the
      surgeon and the patient and has not been reported previously to the best of our
      knowledge. We report our patient with a transient reversal of face turn after
      surgery.

PMID- 21736553
TI  - Strabology Under-represented in Big Eye Literature. In this Issue: Zoran; San
      Diego Rotogravure and AAPOS Annual Meeting Report; Strabometry; Unique Case
      Reports; Eye Candy World; Blog Resumes.

PMID- 21736554
TI  - Remodelling of the endoplasmic reticulum during store-operated calcium entry.
AB  - SOCE (store-operated calcium entry) is a ubiquitous cellular mechanism linking
      the calcium depletion of the ER (endoplasmic reticulum) to the activation of PM
      (plasma membrane) Ca2+-permeable channels. The activation of SOCE channels
      favours the entry of extracellular Ca2+ into the cytosol, thereby promoting the
      refilling of the depleted ER Ca2+ stores as well as the generation of long
      lasting calcium signals. The molecules that govern SOCE activation comprise ER
      Ca2+ sensors [STIM1 (stromal interaction molecule 1) and STIM2], PM Ca2+
      permeable channels {Orai and TRPC [TRP (transient receptor potential) canonical]}
      and regulatory Ca2+-sensitive cytosolic proteins {CRACR2 [CRAC (Ca2+ release
      activated Ca2+ current) regulator 2]}. Upon Ca2+ depletion of the ER, STIM
      molecules move towards the PM to bind and activate Orai or TRPC channels,
      initiating calcium entry and store refilling. This molecular rearrangement is
      accompanied by the formation of specialized compartments derived from the ER, the
      pre-cER (cortical ER) and cER. The pre-cER appears on the electron microscope as
      thin ER tubules enriched in STIM1 that extend along microtubules and that are
      devoid of contacts with the PM. The cER is located in immediate proximity to the
      PM and comprises thinner sections enriched in STIM1 and devoid of chaperones that
      might be dedicated to calcium signalling. Here, we review the molecular
      interactions and the morphological changes in ER structure that occur during the
      SOCE process.

PMID- 21736555
TI  - Histone demethylases in chromatin cross-talks.
AB  - The 'histone code' hypothesis states that chromatin-based regulation of nuclear
      processes such as transcription is brought about by the combination of distinct
      modifications (histone marks) at specific loci. Its correct establishment
      involves chromatin cross-talks, ensuring an ordered and concerted
      deposition/removal of a particular set of modifications that act together to give
      the correct transcriptional outcome. Histone methylation on lysine residues can
      negatively or positively impact on gene transcription, depending on the residue
      and on its degree of methylation. Thanks to this complexity and given the number
      of chromatin 'readers' that can recognize methylated lysine residues, histone
      methylation plays a very special role in specifying the various chromatin states.
      The recent discovery of histone demethylases, which represent a large family of
      enzymes often containing histone modification binding modules, sheds new light on
      cross-talk mechanisms involving methylated residues. In the present review, after
      a brief overview of the various families of histone demethylases, we describe the
      different mechanisms by which they participate in chromatin cross-talks and how
      these mechanisms are integrated to achieve the mutual exclusion or the link
      between chromatin marks, leading to the establishment of the correct histone
      code.

PMID- 21736557
TI  - The coactivator activator CoAA regulates PEA3 group member transcriptional
      activity.
AB  - The PEA3 (polyoma enhancer activator 3) group members [ERM (ETS-related
      molecule), ER81 (ETS-related 81) and PEA3] of the Ets transcription factor family
      are involved in migration and dissemination processes during organogenesis and
      cancer development. In the present study, we report that the hnRNP (heterogeneous
      nuclear ribonucleoprotein)-like protein CoAA (Coactivator activator) interacts
      with the PEA3 group members and modulates their transcriptional activity. We also
      demonstrate that the CoAA YQ domain, containing tyrosine/glutamine-rich
      hexapeptide repeats, is necessary for the interaction, whereas the two N-terminal
      RRMs (RNA recognition motifs) of CoAA are required to enhance transcriptional
      activity. Finally, we show that CoAA is involved in the migration-enhancing
      action of PEA3 on MCF7 human cancer cells, suggesting that CoAA might be an
      important regulator of PEA3 group member activity during metastasis.

PMID- 21736558
TI  - The histone variant H2A.Z interconverts two stable epigenetic chromatin states.
AB  - The nucleosomes occupying the chromosomal start sites of transcription contain
      the histone H2A variant H2A.Z in place of H2A. Upon galactose induction,
      nucleosomes are evicted from the GAL1 locus in Saccharomyces cerevisiae cells.
      H2A.Z (which is encoded by the HTZ1 gene in S. cerevisiae) is required for the
      eviction of the GAL1 promoter nucleosome and for the transcriptional activation
      of the GAL1 gene; however, histones are also important for transcriptional
      repression and we asked in the present paper if H2A.Z also plays a role in the
      glucose repression of the GAL1 promoter. With the help of a fusion of the URA3
      ORF (open reading frame) to the GAL1 promoter, we were able to detect two
      different epigenetic transcription states of the GAL1 promoter in glucose-grown
      cells lacking H2A.Z: a repressed state that is occupied by a H2A-containing
      nucleosome and a derepressed state that is nucleosome-free. These two chromatin
      states are inherited stably through many cell divisions. According to the model
      described in the present paper, the role of H2A.Z is to facilitate the addition
      and removal of promoter nucleosomes and to prevent the formation of unfavourable
      stable epigenetic chromatin structures, which are not in accordance with the
      environmental conditions.

PMID- 21736559
TI  - Effect of substrate features and mutagenesis of active site tyrosine residues on
      the reaction course catalysed by Trypanosoma brucei sterol C-24
      methyltransferase.
AB  - TbSMT [Trypanosoma brucei 24-SMT (sterol C-24-methyltransferase)] synthesizes an
      unconventional 24-alkyl sterol product set consisting of Delta24(25)-,
      Delta24(28)- and Delta25(27)-olefins. The C-methylation reaction requires
      Si(beta)-face C-24-methyl addition coupled to reversible migration of positive
      charge from C-24 to C-25. The hydride shifts responsible for charge migration in
      formation of multiple ergostane olefin isomers catalysed by TbSMT were examined
      by incubation of a series of sterol acceptors paired with AdoMet (S-adenosyl-L
      methionine). Results obtained with zymosterol compared with the corresponding 24
      2H and 27-13C derivatives revealed isotopic-sensitive branching in the hydride
      transfer reaction on the path to form a 24-methyl-Delta24(25)-olefin product
      (kinetic isotope effect, kH/kD=1.20), and stereospecific CH3->CH2 elimination at
      the C28 branch and C27 cis-terminal methyl to form Delta24(28) and Delta25(27)
      products respectively. Cholesta-5,7,22,24-tetraenol converted into ergosta
      5,7,22,24(28)-tetraenol and 24beta-hydroxy ergosta-5,7,23-trienol (new compound),
      whereas ergosta-5,24-dienol converted into 24-dimethyl ergosta-5,25(27)-dienol
      and cholesta-5,7,24-trienol converted into ergosta-5,7,25(27)trienol, ergosta
      5,7,24(28)-trienol, ergosta-5,7,24-trienol and 24 dimethyl ergosta-5,7,25(27)
      trienol. We made use of our prior research and molecular modelling of 24-SMT to
      identify contact amino acids that might affect catalysis. Conserved tyrosine
      residues at positions 66, 177 and 208 in TbSMT were replaced with phenylalanine
      residues. The substitutions generated variable loss of activity during the course
      of the first C-1-transfer reaction, which differs from the corresponding Erg6p
      mutants that afforded a gain in C-2-transfer activity. The results show that
      differences exist among 24-SMTs in control of C-1- and C-2-transfer activities by
      interactions of intermediate and aromatic residues in the activated complex and
      provide an opportunity for rational drug design of a parasite enzyme not
      synthesized by the human host.

PMID- 21736560
TI  - Propranolol modulates the collateral vascular responsiveness to vasopressin via a
      G(alpha)-mediated pathway in portal hypertensive rats.
AB  - Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications
      of portal hypertension and can be controlled with vasoconstrictors. Nevertheless,
      sympathetic tone abnormality and vascular hyporesponsiveness in portal
      hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol,
      a beta-blocker binding the G-protein-coupled adrenoceptor, is a portal
      hypotensive agent. However, whether propranolol influences the collateral
      vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein
      ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion
      model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated
      with vehicle, propranolol (10 MUmol/l), propranolol plus suramin (100 MUmol/l, a
      G(alpha) inhibitor) or suramin pre-incubation. G(alpha) mRNA expression in the
      splenorenal shunt, the most prominent intra-abdominal collateral vessel, was
      measured. In the chronic study, rats received DW (distilled water) or propranolol
      (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration
      response relationship of AVP and G(alpha) mRNA expression were assessed.
      Propranolol pre-incubation elevated the perfusion pressure changes of collaterals
      in response to AVP, which was inhibited by suramin. The splenorenal shunt
      G(alphaq) and G(alpha11) mRNA expression were enhanced by propranolol. The group
      treated with propranolol plus suramin had a down-regulation of G(alpha11) as
      compared with the propranolol group. Chronic propranolol treatment reduced mean
      arterial pressure, PP (portal pressure) and the perfusion pressure changes of
      collaterals to AVP. G(alphas) expression was up-regulated. In conclusion,
      propranolol pre-incubation enhanced the portal-systemic collateral AVP
      responsiveness in portal hypertensive rats, which was related to G(alphaq) and
      G(alpha11) up-regulation. In contrast, the attenuated AVP responsiveness by
      chronic propranolol treatment was related to G(alphas) up-regulation. The
      G(alpha) signalling pathway may be a therapeutic target to control variceal
      bleeding and PP in portal hypertension.

PMID- 21736561
TI  - No evidence of IL21 association with multiple sclerosis in a Swedish population.
AB  - Multiple sclerosis (MS) patients, with a second autoimmune disease after
      lymphocyte depletion, had elevated serum IL-21 before and after treatment which
      correlated to IL21 genotypes. In addition, the IL21 gene has been associated to
      several other autoimmune diseases. However, in a Spanish population there was no
      association to MS. Here, in a Swedish cohort (2090 MS cases and 1732 controls) 12
      single nucleotide polymorphisms (SNPs) tagging IL21 were not associated to
      disease. There was no interaction with risk alleles of IL21R and HLA-DRB1*15.
      Lack of genetic association was confirmed in a meta-analysis with pooled data
      from the present study and the Spanish study. In conclusion, IL21 has not been
      shown to be a major risk gene for MS.

PMID- 21736562
TI  - Simultaneous detection of HFE C282Y, H63D and S65C mutations associated with type
      1 haemochromatosis using a multiplex luminex bead assay.
AB  - Type 1 hereditary haemochromatosis (HH) is a common genetic disorder in
      Caucasoids resulting from mutations in the HFE gene. Routine diagnostic testing
      for type 1 HH involves genotyping for two of these described HFE mutations, C282Y
      and H63D. In some cases typing of a third mutation, S65C is also performed.
      Several techniques have been reported for HFE genotyping and these include
      polymerase chain reaction (PCR)-sequence-specific primers (SSP), PCR-restriction
      fragment length polymorphism (RFLP), PCR-sequence-specific oligonucleotide probe
      (SSOP), real-time PCR followed by melting curve analysis and TaqMan assay. The
      aim of this study was to develop an alternative method to both conventional PCR
      and real-time PCR/TaqMan assay to detect all three HFE mutations in a single
      assay using Luminex technology. DNA controls of known genotypes (n = 109) were
      used to evaluate this approach. These controls were selected to represent the
      three possible genotypes (wild type, mutant, heterozygous) for each mutation.
      Subsequently, blind DNA samples (n = 100) were used to validate this method. This
      new assay was then compared with current techniques (in-house PCR-SSP and TaqMan
      assay). Comparison of genotypes obtained with the Luminex method with those
      previously reported by both in-house PCR-SSP and TaqMan assay showed 100%
      concordance for both DNA controls and blind DNA samples and no discrepancies were
      observed. Allelic frequency for C282Y, H63D and S65C mutations were 22%, 16% and
      2%, respectively. We report here a high-throughput, accurate and robust multiplex
      luminex bead assay for routine clinical testing of C282Y, H63D and S65C mutations
      in the HFE gene.

PMID- 21736563
TI  - Clinical immunology review series: An approach to the patient with a periodic
      fever syndrome.
AB  - The periodic fever syndromes are disorders of innate immunity. They may be
      inherited or acquired and present as recurrent attacks of apparently spontaneous
      self-limiting inflammation without evidence of autoantibodies or infection. Over
      the past decade-and-a-half there has been significant progress in their
      understanding and treatment.

PMID- 21736564
TI  - Impact of Huntington's across the entire disease spectrum: the phases and stages
      of disease from the patient perspective.
AB  - Although Huntington's disease (HD) is a neurodegenerative disease characterized
      by motor, cognitive and behavioural disturbances, there has been little empirical
      data examining what patients are most concerned about throughout the different
      stages of disease, which can span many years. Semi-structured face-to-face
      interviews were individually conducted with 31 people living with different
      stages of Huntington's, from pre-clinical gene carriers to advanced stage. We
      examined how often participants raised issues and concerns regarding the impact
      of Huntington's on everyday life. The Physical/functional theme hardly featured
      pre-clinically, but was strongly present from Stage 1, rose steadily and peaked
      at Stage 5. There were no significant changes between stages for the Emotional,
      Social, and Self themes that all featured across all stages, indicating that
      these issues were not raised more frequently over the course of the disease.
      Likewise, the more rarely mentioned Financial and Legal themes also remained
      similar across stages. However, the Cognitive theme only featured between Stages
      1 and 4, and hardly at all pre-clinically and at Stage 5. These findings provide
      insight into patients' important and unique perspective and have implications for
      the management and development of interventions across the spectrum of HD stages.

PMID- 21736565
TI  - Application of a high-speed breeding technology to apple (Malus * domestica)
      based on transgenic early flowering plants and marker-assisted selection.
AB  - Breeding of apple (Malus * domestica) remains a slow process because of
      protracted generation cycles. Shortening the juvenile phase to achieve the
      introgression of traits from wild species into prebreeding material within a
      reasonable time frame is a great challenge. In this study, we evaluated early
      flowering transgenic apple lines overexpressing the BpMADS4 gene of silver birch
      with regard to tree morphology in glasshouse conditions. Based on the results
      obtained, line T1190 was selected for further analysis and application to fast
      breeding. The DNA sequences flanking the T-DNA were isolated and the T-DNA
      integration site was mapped on linkage group 4. The inheritance and correctness
      of the T-DNA integration were confirmed after meiosis. A crossbred breeding
      programme was initiated by crossing T1190 with the fire blight-resistant wild
      species Malus fusca. Transgenic early flowering F(1) seedlings were selected and
      backcrossed with 'Regia' and 98/6-10 in order to introgress the apple scab Rvi2,
      Rvi4 and powdery mildew Pl-1, Pl-2 resistance genes and the fire blight
      resistance quantitative trait locus FB-F7 present in 'Regia'. Three transgenic
      BC'1 seedlings pyramiding Rvi2, Rvi4 and FB-F7, as well as three other BC'1
      seedlings combining Pl-1 and Pl-2, were identified. Thus, the first transgenic
      early flowering-based apple breeding programme combined with marker-assisted
      selection was established.

PMID- 21736566
TI  - Running the gauntlet: from peptide generation to antigen presentation by MHC
      class I.
AB  - Major histocompatibility complex (MHC) class I molecules provide the molecular
      basis for the comprehensive surveillance of an organism by the cytotoxic arm of
      the adaptive immune system. To exert this function correctly, class I molecules
      must be loaded with peptide ligands of appropriate length, sequence and affinity
      that provide a rapidly updated and sufficiently comprehensive picture of the
      state of the cell. This is accomplished by a sophisticated cellular machinery
      using a blend of cellular house-keeping proteins and dedicated transporters,
      chaperones and peptidases. The last 10 years have seen substantial progress in
      our comprehension of this machinery. It seems now clear that a large proportion
      of MHC class I ligands are derived from short-lived products of the ribosomal
      apparatus, many of which correspond to defective proteins. Despite much effort to
      identify alternative proteolytic pathways, cytosolic production of epitopes still
      appears to depend almost entirely on the proteasome, while cytosolic
      aminopeptidases act mainly to limit antigen presentation. In contrast, clear
      evidence for a critical role of trimming peptidases residing in the endoplasmic
      reticulum has emerged. These enzymes play a role in responses against pathogens
      and are associated with autoimmune diseases, most notably ankylosing spondylitis.
      Much has also been learned about the intricate chaperone interactions in peptide
      loading complexes, especially with respect to the structural role of tapasin
      ERp57 conjugates and to the editing function of tapasin. In contrast, cross
      presentation of exogenous antigens by MHC class I molecules still remains
      somewhat poorly understood and is likely to attract much research effort for
      years to come.

PMID- 21736567
TI  - Differentiation of reproductive and competitive ability in the invaded range of
      Senecio inaequidens: the role of genetic Allee effects, adaptive and nonadaptive
      evolution.
AB  - Genetic differentiation in the competitive and reproductive ability of invading
      populations can result from genetic Allee effects or r/K selection at the local
      or range-wide scale. However, the neutral relatedness of populations may either
      mask or falsely suggest adaptation and genetic Allee effects. In a common-garden
      experiment, we investigated the competitive and reproductive ability of invasive
      Senecio inaequidens populations that vary in neutral genetic diversity,
      population age and field vegetation cover. To account for population relatedness,
      we analysed the experimental results with 'animal models' adopted from
      quantitative genetics. Consistent with adaptive r/K differentiation at local
      scales, we found that genotypes from low-competition environments invest more in
      reproduction and are more sensitive to competition. By contrast, apparent effects
      of large-scale r/K differentiation and apparent genetic Allee effects can largely
      be explained by neutral population relatedness. Invading populations should not
      be treated as homogeneous groups, as they may adapt quickly to small-scale
      environmental variation in the invaded range. Furthermore, neutral population
      differentiation may strongly influence invasion dynamics and should be accounted
      for in analyses of common-garden experiments.

PMID- 21736568
TI  - Attenuation of scratch-induced reactive astrogliosis by novel EphA4 kinase
      inhibitors.
AB  - The EphA4 receptor and its ephrin ligands are involved in astrocytic gliosis
      following CNS injury. Therefore, a strategy aimed at the blockade of EphA4
      signaling could have broad therapeutic interest in brain disorders. We have
      identified novel small molecule inhibitors of EphA4 kinase in specific enzymatic
      and cell-based assays. In addition, we have demonstrated in two in vitro models
      of scratch injury that EphA4 receptor kinase is activated through phosphorylation
      and is involved in the repopulation of the wound after the scratch. A potent
      EphA4 kinase inhibitor significantly inhibited wound closure and reduced the
      accumulation of the reactive astrocytes inside the scratch. We have also shown
      that after the transient focal cerebral ischemia in rats, a large glial scar is
      formed by the accumulation of astrocytes and chondroitin sulfate proteoglycan
      surrounding the infarcted tissue at 7 days and 14 days of reperfusion. EphA4
      protein expression is highly up-regulated in the same areas at these time points,
      supporting its potential role in the glial scar formation and maintenance. Taken
      together, these results suggest that EphA4 kinase inhibitors might interfere with
      the astrogliosis reaction and thereby lead to improved neurological outcome after
      ischemic injury.

PMID- 21736570
TI  - When should tests for unexpected antibodies be done during pregnancy?

PMID- 21736571
TI  - Cesium cessation? An advantage of pathogen reduction treatments.

PMID- 21736572
TI  - Transfusion Medicine Illustrated. The Timken Tank.

PMID- 21736574
TI  - Short-term deviations in temperature during storage of plasma at -40 degrees C do
      not affect its quality.
AB  - BACKGROUND: Little data are available on the suitability of frozen plasma for
      transfusion when stored outside its normal temperature, which is the focus of
      investigation in this study. STUDY DESIGN AND METHODS: Plasma was pooled and
      split to create 10 identical units on each of 24 occasions (12 Group A and O).
      Plasma was frozen and stored at -40 degrees C for 2 weeks and then one of each of
      the 10 identical units was subjected to one of the following deviations in
      storage temperature: -18 degrees C for 1 week, 1 month, or 2 months; -10 degrees
      C for 1 week, 1 month, or 2 months; 4 degrees C for 4, 24, or 72 hours; or stored
      at -40 degrees C (control) before returning all units to -40 degrees C. RESULTS:
      Factor VIII was only significantly reduced when plasma was stored at 4 degrees C
      for 24 hours or more or -10 degrees C for 1 week. For all other arms of the
      study, the majority of units of plasma (>75%) remained above 0.70 IU/mL and more
      than 95% were above the lower limit of normal (0.50 IU/mL). The prothrombin time
      ratio only increased after storage at -10 degrees C for 1 month or more, and the
      activated partial thromboplastin time ratio after storage at 4 degrees C for 24
      hours. None of the deviations in storage resulted in a decrease in fibrinogen
      activity. CONCLUSION: These data suggest that plasma that has been stored at -40
      degrees C and exposed to storage temperatures and times of up to 4 hours at 4
      degrees C, 1 week at -10 degrees C or 2 months at -18 degrees C meets EU
      guidelines and is suitable for transfusion.

PMID- 21736575
TI  - Comparison between bacterial growth in platelets (PLTs) washed with M-sol and
      that in PLT-rich plasma.

PMID- 21736576
TI  - Asystole during stem cell apheresis in a young healthy female volunteer donor.

PMID- 21736577
TI  - H1N1 vaccination and false-positive test results for hepatitis B core antibody in
      health workers.

PMID- 21736579
TI  - Integrating quality, education, lean, and performance management into a culture
      of continuous improvement.

PMID- 21736580
TI  - Six Sigma culture as a management principle.

PMID- 21736581
TI  - An analysis of mobile whole blood collection labor efficiency.
AB  - BACKGROUND: Labor efficiency is desirable in mobile blood collection. There are
      few published data on labor efficiency. The variability in the labor efficiency
      of mobile whole blood collections was analyzed. We determined to improve our
      labor efficiency using lean manufacturing principles. STUDY DESIGN AND METHODS:
      Workflow changes in mobile collections were implemented with the goal of
      minimizing labor expenditures. To measure success, data on labor efficiency
      measured by units/hour/full-time equivalent (FTE) were collected. The labor
      efficiency in a 6-month period before the implementation of changes, and in
      months 1 to 6 and 7 to 12 after implementation was analyzed and compared.
      RESULTS: Labor efficiency in the 6-month period preceding implementation was 1.06
      +/- 0.4 units collected/hour/FTE. In months 1 to 6, labor efficiency declined
      slightly to 0.92 +/- 0.4 units collected/hour/FTE (p = 0.016 vs.
      preimplementation). In months 7 to 12, the mean labor efficiency returned to
      preimplementation levels of 1.09 +/-0.4 units collected/hour/FTE. Regression
      analysis correlating labor efficiency with total units collected per drive
      revealed a strong correlation (R(2) = 0.48 for the aggregate data from all three
      periods), indicating that nearly half of labor efficiency was associated with
      drive size. The lean-based changes in workflow were subjectively favored by
      employees and donors. CONCLUSIONS: The labor efficiency of our mobile whole blood
      drives is strongly influenced by size. Larger drives are more efficient, with
      diminishing returns above 40 units collected. Lean-based workflow changes were
      positively received by employees and donors.

PMID- 21736582
TI  - Poor procedures and quality control among nonaffiliated blood centers in Burkina
      Faso: an argument for expanding the reach of the national blood transfusion
      center.
AB  - INTRODUCTION: The World Health Organization (WHO) recommends the creation of
      national blood transfusion services. Burkina Faso has a CNTS (Centre National de
      Transfusion Sanguine-National Blood Transfusion Center) but it currently covers
      only 53% of the national blood supply versus 47% produced by independent hospital
      blood banks. STUDY DESIGN: To evaluate blood collection, testing, preparation,
      and prescription practices in the regions of Burkina Faso that are not covered by
      the CNTS, a cross-sectional survey was conducted. METHODS: Data were collected by
      trained professionals from May to June 2009 at 42 autonomous blood centers not
      covered by the CNTS. RESULTS: Blood collection was supervised in all sites by
      laboratory technicians without specific training. There was no marketing of
      community blood donation nor mobile collection. Donation was restricted to
      replacement (family) donors in 21.4% of sites. Predonation screening of donors
      was performed in 63.4% of sites, but some did not use written questionnaires.
      Testing for HIV, hepatitis B virus, and syphilis was universal, although some
      sites did not screen for hepatitis C virus. In 83.3% of the sites, blood typing
      was performed without reverse ABO typing. In 97.6% of the sites, nurses acted
      alone or in conjunction with a physician to order blood transfusions. CONCLUSION:
      Shortcomings in non-CNTS blood centers argue for the development of a truly
      national CNTS. Such a national center should coordinate and supervise all blood
      transfusion activities, and is the essential first step for improving and
      institutionalizing blood transfusion safety and efficacy in a developing country.

PMID- 21736583
TI  - Knowledge of food and drug administration reportable deviations.
AB  - BACKGROUND: As early as 2001, the Food and Drug Administration (FDA) required
      blood centers and hospital transfusion services to report events associated with
      testing, storage, or distribution of blood products that deviated from current
      good manufacturing practices or affected the safety, purity, or potency of the
      product. Between 2004 and 2009, an average of only 8.6% of hospitals reported
      blood product deviations. STUDY DESIGN AND METHODS: Case scenarios designed to
      evaluate knowledge of FDA reportable deviations were developed and sent for
      evaluation to the Center for Biologics Evaluation and Research (CBER) and FDA
      division directors for FDA reportable deviations. A final survey containing eight
      cases was launched in a web-based online survey tool and sent to blood bank
      medical technologists. Additional information was queried regarding job
      title/responsibilities and the size of the blood center and/or transfusion
      service. RESULTS: There were 176 respondents to the survey. Only 5.7% (10/176)
      answered all questions correctly. Analysis by job title and place of employment
      revealed no correlation to the number of correct responses. More importance was
      attached to deviations involving quality control, blood bank identification, unit
      specifications, and antibody identification. Less importance was attached to
      deviations involving phlebotomist's initials, failure to issue units in the
      computer, and using a recent sample from a previous hospitalization. CONCLUSION:
      This study revealed that blood bankers did not have clear understanding of what
      constituted an FDA reportable occurrence. Size or type of blood establishment or
      individual job title was not associated with more knowledge of FDA reportable
      deviations.

PMID- 21736584
TI  - A model for blood components processing.
AB  - BACKGROUND: Blood component therapy is advantageous in terms of increasing the
      effective availability of blood units and reducing the transfusion-related risks.
      One unit of blood can be separated into components and made available to multiple
      patients by transfusing suitable components. It is often believed that most, if
      not all, of the blood should be fractionated. But the process of componentizing
      increases the availability of blood products at the expense of increased costs of
      holding, processing, and wastage at a blood bank. The objective of this study was
      to determine the optimum level of components to be produced at a blood bank given
      its objectives and context. STUDY DESIGN AND METHODS: We developed a simulation
      based model to determine the optimum amount of fresh blood to be fractionated at
      a blood bank operating in southern India was developed. The simulation model is a
      virtual representation of an actual blood bank, and it can help the administrator
      to test the effects of changing the level of components production on the overall
      blood bank performance. RESULTS: The results from the model suggest that it may
      not be optimal for the chosen blood bank to componentize large amounts of fresh
      blood as it leads to high costs of operation and huge wastage in the system.
      CONCLUSIONS: The same methodology can be applied to determine the optimum level
      of componentizing at other blood banks by providing appropriate inputs to the
      simulation model.

PMID- 21736586
TI  - What happens to abstracts accepted for poster presentation at EAACI Congresses?

PMID- 21736585
TI  - A roundtable discussion: from thoughts on supply and demand to what keeps us up
      at night.

PMID- 21736587
TI  - Safety of oral robenacoxib in the cat.
AB  - The safety of robenacoxib, a nonsteroidal anti-inflammatory drug with high
      selectivity for inhibition of the cyclooxygenase (COX)-2 isoform of COX, was
      investigated in the cat in two randomized, blinded, placebo-controlled, parallel
      group studies. Robenacoxib was administered orally to healthy young domestic
      short-hair cats at dosages of 0 (placebo), 5 and 10 mg/kg once daily for 28 days
      (study 1) and at 0 (placebo), 2, 6 and 10 mg/kg twice daily for 42 days (study
      2). The recommended minimum dosage for robenacoxib tablets in cats is 1 mg/kg
      once daily (range 1-2.4 mg/kg). Relative to placebo treatment, no toxicologically
      significant effects of robenacoxib were recorded in either study, based on
      general observations of health, haematological and clinical chemistry variables
      and urinalyses in life, and by post mortem organ weight, gross pathology and
      histopathology assessments. Pharmacokinetic-pharmacodynamic simulations indicated
      that all dosages of robenacoxib were associated with marked inhibition of COX-2
      at peak effect (median I(max) 97.8-99.4% inhibition) with lesser inhibition of
      COX-1 (median I(max) 26.8-58.3% inhibition). Inhibition of the COXs was short
      lasting, with >10% median inhibition persisting for 4.0 h for COX-2 and 1.5 h for
      COX-1. These levels of inhibition of COX-1 and COX-2 twice daily with robenacoxib
      were not associated with any detectable toxicity, suggesting that, as previously
      described in dogs, the high safety index of robenacoxib in cats may be related to
      a combination of its high COX-2 selectivity and short residence time in the
      central compartment.

PMID- 21736588
TI  - Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and
      intramuscular injection.
AB  - A single dose of florfenicol (Nuflor((r))) was administered to eight healthy
      adult alpacas at 20 mg/kg intramuscular (i.m.) and 40 mg/kg subcutaneous (s.c.)
      using a randomized, cross-over design, and 28-day washout period. Subsequently,
      40 mg/kg florfenicol was injected s.c. every other day for 10 doses to evaluate
      long-term effects. Maximum plasma florfenicol concentrations (C(max), measured
      via high-performance liquid chromatography) were achieved rapidly, leading to a
      higher C(max) of 4.31+/-3.03 MUg/mL following administration of 20 mg/kg i.m.
      than 40 mg/kg s.c. (C(max): 1.95+/-0.94 MUg/mL). Multiple s.c. dosing at 48 h
      intervals achieved a C(max) of 4.48+/-1.28 MUg/mL at steady state. The area under
      the curve and terminal elimination half-lives were 51.83+/-11.72 MUg/mL.h and
      17.59+/-11.69 h after single 2 mg/kg i.m. dose, as well as 99.78+/-23.58 MUg/mL.h
      and 99.67+/-59.89 h following 40 mg/kg injection of florfenicol s.c.,
      respectively. Florfenicol decreased the following hematological parameters after
      repeated administration between weeks 0 and 3: total protein (6.38 vs. 5.61 g/dL,
      P<0.0001), globulin (2.76 vs. 2.16 g/dL, P<0.0003), albumin (3.61 vs. 3.48 g/dL,
      P=0.0038), white blood cell count (11.89 vs. 9.66*10(3)/MUL, P<0.044), and
      hematocrit (27.25 vs. 24.88%, P<0.0349). Significant clinical illness was
      observed in one alpaca. The lowest effective dose of florfenicol should thus be
      used in alpacas and limited to treatment of highly susceptible pathogens.

PMID- 21736589
TI  - A novel function for a redox-related LEA protein (SAG21/AtLEA5) in root
      development and biotic stress responses.
AB  - SAG21/AtLEA5 belongs to the late embryogenesis-associated (LEA) protein family.
      Although it has been implicated in growth and redox responses, its precise roles
      remain obscure. To address this problem, we characterized root and shoot
      development and response to biotic stress in SAG21/AtLEA5 over-expressor (OEX)
      and antisense (AS) lines. AS lines exhibited earlier flowering and senescence and
      reduced shoot biomass. Primary root length was reduced in AS lines, as was the
      number of laterals relative to the primary root. Root hair number was unchanged
      but root hair length was proportional to SAG21/AtLEA5 expression level, with
      longer root hairs in OEX lines and shorter root hairs in AS, relative to wild
      type. Growth of the fungal nectroph, Botrytis cinerea and of a virulent bacterial
      pathogen (Pseudomonas syringae pv. tomato) was affected by SAG21/AtLEA5
      expression; however, growth of an avirulent P.syringae strain was unaffected. A
      SAG21/AtLEA5-YFP fusion was localized to mitochondria, raising the intriguing
      possibility that SAG21 interacts with proteins involved in mitochondrial ROS
      signalling, which in turn, impacts on root development and pathogen responses.

PMID- 21736590
TI  - Infestation of potato (Solanum tuberosum L.) by the peach-potato aphid (Myzus
      persicae Sulzer) alters cellular redox status and is influenced by ascorbate.
AB  - The peach-potato aphid (Myzus persicae Sulzer) is a major pest of potato (Solanum
      tuberosum L.) but the molecular characterization of this interaction particularly
      with regard to oxidants and antioxidants remains to be undertaken. Aphid colonies
      reared on potato leaves containing high ascorbate were twice the size of those
      grown on leaves with low ascorbate. Infestation-dependent decreases in the
      abundance of key transcripts such as chloroplastic FeSOD, peroxisomal catalase 2,
      PR1 and JAZ1 preceded detectable leaf H(2)O(2) or polyphenol accumulation. The
      leaf glutathione pool was increased 48 h after infestation, but the amount of
      ascorbate was unchanged. The ascorbate/dehydroacorbate (DHA) ratio was lower at
      48 h but the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG)
      was unchanged. While DHA reductase and GSSG reductase activities were unaffected
      by aphid feeding, non-specific peroxidase activities were enhanced 48 h following
      aphid infestation. Brown ethanol-insoluble deposits were observed close to leaf
      veins following aphid infestation. Taken together, the results demonstrate that
      high ascorbate favours aphid colony expansion and that perturbations in the leaf
      antioxidant system are intrinsic to the potato leaf response to aphids. Moreover,
      these changes together with the induction of hormone-related transcripts precede
      the deposition of defence-associated oxidized polyphenols along the stylet track.

PMID- 21736591
TI  - Responses of barley root and shoot proteomes to long-term nitrogen deficiency,
      short-term nitrogen starvation and ammonium.
AB  - Cereals are major crops worldwide, and improvement of their nitrogen use
      efficiency is a crucial challenge. In this study proteins responding to N supply
      in barley roots and shoots were analysed using a proteomics approach, to provide
      insight into mechanisms of N uptake and assimilation. Control plants grown
      hydroponically for 33 d with 5 mm nitrate, plants grown under N deficiency (0.5
      mm nitrate, 33 d) or short-term N starvation (28 d with 5 mm nitrate followed by
      5 d with no N source) were compared. N deficiency caused changes in C and N
      metabolism and ascorbate-glutathione cycle enzymes in shoots and roots. N
      starvation altered proteins of amino acid metabolism in roots. Both treatments
      caused proteome changes in roots that could affect growth. Shoots of plants grown
      with ammonium as N source (28 d with 5 mm nitrate followed by 5 d with 5 mm
      ammonium) showed responses similar to N deficient shoots, characterized by
      turnover of ribulose 1.5-bisphosphate carboxylase/oxygenase (Rubisco) and
      increases in proteins of the chloroplastic transcription and translation
      machinery. Identified proteins in 67 and 49 varying spots in roots and shoots
      respectively, corresponded to 62 functions and over 80 gene products,
      considerably advancing knowledge of N responses in barley.

PMID- 21736592
TI  - A longitudinal investigation of the rejection-identification hypothesis.
AB  - The rejection-identification model (RIM; Branscombe, Schmitt, & Harvey, 1999) is
      supported by a number of previous studies (e.g., Schmitt, Branscombe,
      Kobrynowicz, & Owen, 2002; Schmitt, Spears, & Branscombe, 2003). This suggests
      that rejection by an outgroup can lead minority group members to identify more
      with their ingroup, thereby buffering them from the negative effects of
      discrimination. However, contradictory findings have been produced by other
      research (e.g., Eccleston & Major, 2006; Major, Quinton, & Schmader, 2003; McCoy
      & Major, 2003; Sellers & Shelton, 2003), suggesting that the relationship between
      rejection and identification is far from being completely understood. In the
      present study, we followed a cohort of 113 international students for a period of
      2 years. The study sought to extend the previous work in two important ways.
      First, it examined the RIM within a longitudinal perspective. Second, building on
      important work on the multidimensionality of social identification (e.g.,
      Ellemers, Kortekaas, & Ouwerkerk, 1999; Jackson, 2002), it tested the RIM using a
      three-dimensional approach to group identification. Results supported the
      predictions of the RIM and indicated that perceived discrimination causes
      minority group identification and not the reverse. The multidimensional approach
      also served to reveal a specific effect of discrimination on the cognitive
      components of identification.

PMID- 21736594
TI  - Presurgical hand antisepsis: concepts and current habits of veterinary surgeons.
AB  - OBJECTIVE: To assess current habits for surgical hand preparation among
      veterinary surgical specialists and to compare data with current guidelines for
      hand asepsis techniques. STUDY DESIGN: Survey of veterinary surgical specialists.
      SAMPLE POPULATION: Diplomates of the American (ACVS) and European Colleges of
      Veterinary Surgeons (ECVS). METHODS: An internet-based survey of hand preparation
      methods before surgical procedures was conducted of 1300 listed ACVS and ECVS
      Diplomates. RESULTS: A 42.6% response rate was obtained. Approximately, 80% of
      respondents use disinfecting soaps as a primary method for hand antisepsis. Of
      those, 81% use chlorhexidine-based scrubs and 7% use a neutral soap followed by a
      hydroalcoholic solution. CONCLUSIONS: Contrary to current recommendations of the
      World Health Organization and scientific evidence supporting use of hydro
      alcoholic rubs for presurgical hand preparation, veterinary surgical specialists
      still use surgical scrub solutions containing disinfecting soaps.

PMID- 21736595
TI  - Bone grafting and tibial tuberosity advancement.

PMID- 21736597
TI  - In memoriam: John F. (Jack) Fessler.

PMID- 21736598
TI  - Increased lymphatic vessel density and lymphangiogenesis in inflammatory bowel
      disease.
AB  - BACKGROUND: Involvement of the lymphatic system in inflammatory bowel disease
      (IBD) has been suggested. AIMS: To examine the density and distribution of
      lymphatic vessels (LV) within inflamed and non-inflamed wall sections of IBD
      patients compared with controls, and to evaluate expression of major
      lymphangiogenic factors. METHODS: Ileal and colon specimens of 22 patients with
      Crohn's disease (CD), 16 patients with ulcerative colitis (UC) and 11 controls
      were studied. Quantification of LV was performed using immunohistochemistry with
      podoplanin and D2-40 antibodies on seven randomly selected fields. Mucosal
      expression of podoplanin and lymphangiogenic factor mRNA was measured using PCR.
      RESULTS: In CD patients, lymphatic density was significantly increased in non
      inflamed and inflamed ileal (P < 0.01 and P < 0.001) and colonic (P < 0.01 and P
      < 0.001) mucosa compared to controls. Podoplanin mRNA levels were similar in non
      inflamed mucosal areas and controls, whereas a four- and sixfold increase was
      seen in inflamed ileal and colonic areas (P < 0.05). In UC, lymphatic density
      increased fourfold in non-inflamed (P < 0.001) and fivefold in inflamed colonic
      mucosa (P < 0.001) compared with controls. An increase in podoplanin mRNA levels
      was seen in both non-inflamed and inflamed areas (P < 0.01) compared with
      controls. In CD and UC, lymphatics were found throughout the inflamed mucosa,
      including the upper half of the lamina propria. Expression of lymphangiogenic
      factors was similar in patients and controls. CONCLUSIONS: Increased density of
      lymphatic vessels is a constant feature of IBD and is present in non-inflamed
      areas. It is transmural in CD and confined to the mucosa in UC. Its origin
      remains unclear.

PMID- 21736599
TI  - Subgingival debridement of periodontal pockets by air polishing in comparison
      with ultrasonic instrumentation during maintenance therapy.
AB  - AIM: The objective was to determine clinical and microbiological effects and
      perceived treatment discomfort of root debridement by subgingival air polishing
      compared with ultrasonic instrumentation during supportive periodontal therapy
      (SPT). MATERIAL AND METHODS: The trial was conducted as a split-mouth designed
      study of 2-month duration including 20 recall patients previously treated for
      chronic periodontitis. Sites with probing pocket depth (PPD) of 5-8 mm and
      bleeding on probing (BoP+) in two quadrants were randomly assigned to subgingival
      debridement by (i) glycine powder/air polishing applied with a specially designed
      nozzle or (ii) ultrasonic instrumentation. Clinical variables were recorded at
      baseline, 14 and 60 days post-treatment. Primary clinical efficacy variable was
      PPD reduction. Microbiological analysis of subgingival samples was performed
      immediately before and after debridement, 2 and 14 days post-treatment. RESULTS:
      Both treatment procedures resulted in significant reductions of periodontitis
      associated bacterial species immediately and 2 days after treatment, and in
      significant reduction in BoP, PPD and relative attachment level at 2 months.
      There were no statistically significant differences between the treatment
      procedures at any of the examinations intervals. Perceived treatment discomfort
      was lower for air polishing than ultrasonic debridement. CONCLUSION: This short
      term study revealed no pertinent differences in clinical or microbiological
      outcomes between subgingival air polishing and ultrasonic debridement of moderate
      deep pockets in SPT patients.

PMID- 21736600
TI  - Evidence grade associating periodontitis with preterm birth and/or low birth
      weight: II: a systematic review of randomized trials evaluating the effects of
      periodontal treatment.
AB  - AIM: The aim of this systematic review was to evaluate whether maternal
      periodontal disease treatment (MPDT) can reduce the incidence of preterm birth
      (PB) and/or low birth weight (LBW). METHODS: The Cochrane Central Register of
      Controlled Trials, MEDLINE and EMBASE were searched for entries up to October
      2010 without restrictions regarding the language of publication. Only randomized
      controlled clinical trials (RCTs) that evaluated the effect of MPDT on birth term
      and birth weight were included. The search was conducted by two independent
      reviewers and random-effects meta-analyses were conducted methodically. RESULTS:
      Thirteen RCTs provided data, but only five trials were considered to be at a low
      risk of bias. The results of eight studies (61.5%) showed that MPDT may reduce
      the incidence of PB and/or LBW. However, the results of all meta-analyses showed
      contrasting results for PB [RR: 0.88 (95% CI: 0.72, 1.09)], LBW [RR: 0.78 (95%
      CI: 0.53, 1.17)] and PB/LBW [RR: 0.52 (95% CI: 0.08, 3.31)]. CONCLUSION: The
      results of this review show that MPDT did not decrease the risk of PB and/or LBW;
      however, the influence of specific aspects that were not investigated (disease
      diagnosis, extension and severity and the success of MPDT) should be evaluated by
      future RCTs.

PMID- 21736601
TI  - ABCC1 polymorphism Arg723Gln (2168G> A) is associated with lung cancer
      susceptibility in a Chinese population.
AB  - 1. In a previous in vitro study, we showed that the Arg723Gln (2168G > A)
      polymorphism significantly ABCC1-induced multidrug resistance. The aim of the
      present study was to further investigate the association of this polymorphism
      with lung cancer susceptibility and chemotherapy response in a Chinese
      population. 2. A total of 77 lung cancer patients (54 men, 23 women) and 71
      cancer-free controls (49 men, 22 women) were enrolled in the study. Genomic DNA
      was extracted from peripheral blood and all samples were genotyped using
      polymerase chain reaction-restriction fragment length polymorphism. 3.
      Individuals carrying the 723Gln (A) allele have a 3.4-fold increased risk
      (adjusted odds ratio (OR) 3.42; 95% confidence interval (CI) 1.29-9.06; P =
      0.013) of lung cancer compared with wild-type individuals. Further stratified
      analysis indicated that older individuals (> 50 years) carrying the 723Gln (A)
      allele have the highest susceptibility to lung cancer (adjusted OR 4.10; 95% CI
      1.25-13.48; P = 0.020). However, no substantial association was found between the
      Arg723Gln (2168G > A) polymorphism and chemotherapy response in Chinese lung
      cancer patients. 4. In conclusion, the Arg723Gln (2168G > A) polymorphism of
      ABCC1 appears to be a potential susceptibility marker for lung cancer in the
      Chinese population, especially in older people.

PMID- 21736602
TI  - Aliskiren increases bradykinin and tissue kallikrein mRNA levels in the heart.
AB  - 1. Aliskiren is a renin inhibitor with an IC(50) of 0.6 nmol/L for human renin,
      4.5 nmol/L for mouse renin and 80 nmol/L for rat renin. 2. In the present study,
      we compared the effects of aliskiren (10 mg/kg per day), the angiotensin
      converting enzyme inhibitor perindopril (0.2 mg/kg per day) and their combination
      on angiotensin and bradykinin peptides in female heterozygous (mRen-2)27 rats,
      transgenic for the mouse renin gene. 3. All three treatments produced similar
      reductions in systolic blood pressure, heart weight and plasma aldosterone levels
      and reduced angiotensin II levels in lung, but only perindopril and the
      combination reduced angiotensin II levels in kidney of (mRen-2)27 rats. In
      contrast, aliskiren and the combination, but not perindopril alone, increased
      cardiac bradykinin levels. Aliskiren increased immunostaining for tissue
      kallikrein in the heart and reduced cardiac fibrosis. 4. We investigated the
      mechanism underlying the increase in bradykinin levels following aliskiren
      treatment in Sprague-Dawley rats, in which aliskiren has a lower potency for
      renin inhibition. Aliskiren (10 mg/kg per day) reduced renal angiotensin levels
      within 24 h, but treatment for > 24 h was required to increase cardiac bradykinin
      levels. Moreover, 3 mg/kg per day aliskiren increased cardiac bradykinin levels,
      but did not reduce renal angiotensin levels. Aliskiren did not potentiate the
      hypotensive effects of bradykinin; however, it increased tissue kallikrein, but
      not plasma kallikrein, mRNA levels in the heart. 5. These data demonstrate that
      the aliskiren-induced increase in cardiac bradykinin levels is independent of
      renin inhibition and changes in bradykinin metabolism, but is associated with
      increased tissue kallikrein gene expression.

PMID- 21736603
TI  - A dynamic context model of interactive behavior.
AB  - A dynamic context model of interactive behavior was developed to explain results
      from two experiments that tested the effects of interaction costs on encoding
      strategies, cognitive representations, and response selection processes in a
      decision-making and a judgment task. The model assumes that the dynamic context
      defined by the mixes of internal and external representations and processes are
      sensitive to the interaction cost imposed by the task environment. The model
      predicts that changes in the dynamic context may lead to systematic biases in
      cognitive representations and processes that eventually influence decision-making
      and judgment outcomes. Consistent with the predictions by the model, results from
      the experiments showed that as interaction costs increased, encoding strategies
      and cognitive representations shifted from perception-based to memory-based.
      Memory-based comparisons of the stimuli enhanced the similarity and dominance
      effects, and led to stronger systematic biases in response outcomes in a choice
      task. However, in a judgment task, memory-based representations enhanced only the
      dominance effects. Results suggested that systematic response biases in the
      dominance context were caused by biases in the cognitive representations of the
      stimuli, but response biases in the similarity context were caused by biases in
      the comparison process induced by the choice task. Results suggest that changes
      in interaction costs not only change whether information was assessed from the
      external world or from memory but also introduce systematic biases in the
      cognitive representation of the information, which act as biased inputs to the
      subsequent decision-making and judgment processes. Results are consistent with
      the idea of interactive cognition, which proposes that representations and
      processes are contingent on the dynamic context defined by the information flow
      between the external task environment and internal cognition.

PMID- 21736604
TI  - Case of Gardner-Diamond syndrome after intramuscular stimulation.

PMID- 21736605
TI  - Quality of life and clinical features in Swedish children with psoriasis.
AB  - Psoriasis is a common, chronic disease and in one-third of the patients it begins
      during the first 2 decades of life. The burdens of psoriasis are many, and some
      can be assessed with quality of life questionnaires. The aim was to investigate
      the impact of childhood psoriasis on quality of life in children and their
      parents and to correlate certain clinical findings with quality of life. Forty
      five Swedish children (4-16 years, 28 girls) with psoriasis, and their parents,
      were investigated with the validated questionnaires Children's Dermatology Life
      Quality Index (5-16 years, n = 42), The Infant's Dermatitis Quality of Life Index
      (4 years, n = 3), and Dermatitis Family Impact (n = 45), the two latter with the
      word eczema replaced by psoriasis. Clinical examination was performed, and
      psoriasis severity was scored with Psoriasis Area and Severity Index. Chronic
      plaque psoriasis was the most common clinical type (87%). Four of the children
      had joint complaints. Ninety-three percent had pruritus the preceding 3 days.
      Ninety-three percent were receiving treatment. Median Psoriasis Area and Severity
      Index score was 3.3 (range 0.5-12.3). Median score for the Infant's Dermatitis
      Quality of Life Index was 4.0 (range 2-12), for Children's Dermatology Life
      Quality Index 4.0 (0-24), and for Dermatitis Family Impact questionnaire 4.0 (0
      25). No significant gender difference existed. The Children's Dermatology Life
      Quality Index scores were higher for younger (5-8 yrs) than older (9-16 yrs)
      children and higher for those with joint complaints. The Dermatitis family impact
      scores correlated significantly with Children's Dermatology Life Quality Index
      and Psoriasis Area and Severity Index scores, but the Children's Dermatology Life
      Quality Index did not correlate with Psoriasis Area and Severity Index. The
      Visual Analog Scale and quality of life scores were significantly correlated.
      Psoriasis in children affects quality of life in the subjects and their parents.
      Joint complaints and pruritus significantly impair quality of life.

PMID- 21736606
TI  - Dyskeratosis congenita--two siblings with a new missense mutation in the DKC1
      gene.
AB  - Dyskeratosis congenital is reported in two siblings. They presented with the
      classic triad of mucocutaneous features: leukoplakia of the tongue, dystrophic
      nails, and a widespread reticulate pigmentation on the neck and upper chest. A
      genetic analysis was performed and a new missense mutation S356P, hemizygous, was
      identified in the DKC1 gene in both patients. Acitretin was started at a low-dose
      in both patients, resulting in clinical improvement and important, positive
      psychosocial effects.

PMID- 21736607
TI  - A call to action--preventing community violence.

PMID- 21736608
TI  - Sociodemographic correlates of behavioral problems among rural Chinese
      schoolchildren.
AB  - OBJECTIVE: To investigate the problem behaviors of children from grades 4-6 and
      associated factors in the rural Hunan province of China. DESIGN AND SAMPLE:
      Randomized cluster sampling in 3 rural areas of the Hunan province was used. 435
      subjects were randomly selected from grades 4-6. MEASURES: A researcher-designed
      questionnaire was used to find influential demographic, parental, and
      socioeconomic factors. The prediction test of problem children (PPCT) was used to
      assess problem behaviors. RESULTS: The prevalence of the early child problem
      behaviors in our sample was 17.44%. Associated factors include gender,
      willingness to attend school, parents' expectations of the children's educational
      degree, parents working outside the home (left-behind children), and children's
      feeling of their parents' understanding of them. CONCLUSIONS: The prevalence of
      children with problem behaviors was higher in rural areas in Hunan than in China
      as a whole. This may be partly explained by the fact that parents must often work
      in the cities and leave their children behind at home, increasing the chances
      that those children develop behavioral problems. This phenomenon also applies in
      other developing countries, making it a public health concern. Therefore, there
      is a need to prevent problem behaviors through collaboration among families,
      schools, and society.

PMID- 21736609
TI  - Use of school nurse services among poor ethnic minority students in the urban
      Pacific Northwest.
AB  - OBJECTIVE: To determine whether patterns in student use of school nurse services
      existed according to poverty, race, and ethnicity. DESIGN AND SAMPLE: Cross
      sectional descriptive study of 51,767 visits to school nurses made by 12,797
      middle and high school students was conducted. Data were collected and analyzed
      by race, ethnicity, and poverty. MEASURES: Individual-level quantitative data on
      student visits to school nurses were collected via the School Nurse Entry
      Database. Numbers and types of student visits were measured, along with the
      demographic characteristics of student visitors. RESULTS: Poverty was the largest
      driver of visits to school nurses among all racial and ethnic groups. Poverty was
      a larger influence on White students' use of services, suggesting that factors
      related to race, ethnicity, or culture may have larger effects on promoting
      visits to school nurses by students of color. Subethnic Asian and Hispanic groups
      showed visit patterns that deviated from aggregated visit rates. CONCLUSIONS:
      Knowledge of visit patterns among poor, ethnic, and subethnic populations is
      important-and particularly urgent with the advent of national health reform-in
      informing and improving public health and school nursing policy and practice.

PMID- 21736610
TI  - Emergency contraception in Iowa pharmacies before and after over-the-counter
      approval.
AB  - OBJECTIVES: To compare availability of emergency contraception in Iowa
      pharmacies, before and after the U.S. Food and Drug Administration (FDA) approved
      over-the-counter sales and identify reasons why over-the-counter, emergency
      contraception might still not be available in some Iowa pharmacies. DESIGN AND
      SAMPLE: Secondary analysis of data collected for an existing, descriptive study.
      A total of 906 pharmacies were identified; 405 (56.8%) pharmacies participated
      before, and 308 (43.2%) after the FDA policy change. MEASURES: Data collected via
      a scripted telephone survey. RESULTS: After the FDA changed its policy and
      allowed over-the-counter sales of emergency contraception, the percentage of Iowa
      pharmacies offering emergency contraception increased from 57.8% to 70%. In the
      before sampling, 67.5% reported a perceived lack of demand as the primary reason
      for not carrying emergency contraception 66.7% reported this rationale in the
      after group. Other reasons included store policy, and moral, religious, or
      personal reasons. Pharmacists were surprisingly uninformed about the action of
      emergency contraception; before the FDA approved over-the-counter sales 53%
      believed the drugs primarily worked by blocking implantation of a fertilized egg.
      Indeed, even after FDA approved over-the-counter sales, 38% of pharmacists still
      believed that emergency contraception was comparable to an abortifacient. In
      addition, before the policy changed, 43.8% of pharmacists accepted emergency
      contraception as safe for teenagers; this percentage fell to 27.9% after the
      policy change. CONCLUSIONS: Significant increases in the carrying of emergency
      contraception suggest the policy did succeed in increasing access. Despite this,
      barriers to access exist. Further research should explore why pharmacies might
      not carry emergency contraception.

PMID- 21736611
TI  - Psychosocial impact of a positive HSV-2 diagnosis on adults with unrecognized HSV
      2 infection.
AB  - OBJECTIVE: To evaluate the current research on the psychosocial impact of a
      positive herpes simplex virus type 2 (HSV-2) diagnosis on asymptomatic adults.
      DESIGN AND SAMPLE: A structured review of PubMed, CINAHL, and MEDLINE resulted in
      8 articles published between 2000 and 2008. MEASURES: Articles were included if
      they investigated psychosocial reactions to HSV serological testing, including
      asymptomatic individuals, and used measurement instruments with adequate
      psychometric properties. RESULTS: The studies included participants of various
      backgrounds, including individuals with a new HSV-2 diagnosis concurrently
      receiving human immunodeficiency virus treatment, students within a university
      setting, and an HMO population. Current research indicates that a diagnosis of
      HSV-2 does not result in persistent psychosocial morbidity. However, studies that
      assessed for more nuanced reactions noted an impact on quality of life related to
      herpes. CONCLUSIONS: Further research is needed to confirm these findings among
      varied populations, to explore quality of life following HSV screening, and to
      identify the characteristics that may make particular individuals more
      susceptible to adverse psychological consequences.

PMID- 21736612
TI  - The nature of occupational violence against taxicab drivers.
AB  - OBJECTIVE: This research sought to expand evidence about the nature of
      occupational violence against taxicab drivers and provide further understanding
      of occupational violence from their perspective. DESIGN AND SAMPLE: Qualitative
      research using hermeneutic analysis was conducted. Sixteen taxicab drivers were
      interviewed, transcripts were analyzed, and the themes describing the nature of
      occupational violence were identified. RESULTS: Study participants reported
      exposure to violence, including incidents that involved money, interpersonal
      violence, encounters during night shift, and physical violence and weapons.
      Verbatim quotes illustrated violent acts that taxicab drivers experienced.
      CONCLUSIONS: The study findings reveal that taxicab drivers are commonly exposed
      to violence on the job. Acts that the participants reported as violence included
      racism, disrespect, verbal abuse, and physical violence. These incidents
      highlighted the perception of foreign-born drivers that their risk for violence
      on the job is increased because they are members of a visible minority.
      Community/public health nursing practice implications include actions that: (a)
      reduce psychosocial risks and disparities from exposure to occupational violence,
      (b) develop effective prevention measures that reduce exposure of taxicab drivers
      to violence, (c) consider this worker population when planning community violence
      prevention programs, and (d) influence public policy related to taxicab driver
      safety. The investigator advocates and offers recommendations for future research
      about the nature, effects, and prevention of occupational violence against
      taxicab drivers.

PMID- 21736613
TI  - The impact of Web-delivered education on preceptor role self-efficacy and
      knowledge in public health nurses.
AB  - OBJECTIVE: Preceptors are an essential component in preparing student nurses to
      become practicing public health nurses. Preparation for the preceptor role is
      important for achieving a quality learning experience for students. This study
      was conducted to explore the relationship between completion of a Web-delivered
      preceptor education program and both knowledge of the preceptor role and self
      efficacy to perform in the preceptor role. DESIGN AND SAMPLE: This study used a
      pretest-posttest, quasi-experimental design. The participants were experienced
      public health nurses (n=31) working in one state in the United States. MEASURES:
      Pretest and posttest Web-delivered survey using the preceptor self-efficacy
      questionnaire and an instrument assessing knowledge gain. INTERVENTION: A Web
      delivered preceptor education program tailored for public health nurses. RESULTS:
      The program was associated with improved self-efficacy scores at both the
      immediate and the 3-month posttest, and with increased knowledge of the preceptor
      role evident at the immediate posttest only. Self-efficacy scores were
      independent of knowledge scores. Preceptor age was not correlated with self
      efficacy or knowledge scores. Nurses with higher levels of education demonstrated
      higher self-efficacy scores in all 3 measurements. CONCLUSIONS: Web-delivered
      continuing education targeted to public health nurse preceptors is an effective
      method to increase confidence and knowledge for the preceptor role.

PMID- 21736614
TI  - An argument for practice-based public health research on sexually transmitted
      infection management.
AB  - Over the last few years, the rates of certain sexually transmitted infections
      (STIs) have again begun to rise in Canada, the United Kingdom, and the United
      States. Paradoxically, these increases are occurring at the same time that
      greater numbers of researchers are publishing reports about highly successful
      safer sex interventions. Research that investigates this phenomenon reveals that
      the majority of new STIs management initiatives never reach day-to-day practice
      after the research period has terminated. In reaction to this, it is suggested
      here that researchers should begin developing their STIs management interventions
      in practice-based settings, with a strong emphasis being placed on ensuring
      target group input from the outset. While such an approach may not be able to
      discern precise cause-and-effect relationships, it has the benefit of enhancing
      use after researchers have withdrawn their support. The benefits that arise from
      long-term and widespread use of this approach may therefore outweigh the
      advantages that can occur from developing highly efficacious, but unused, STIs
      management strategies.

PMID- 21736615
TI  - A syndemic model of substance abuse, intimate partner violence, HIV infection,
      and mental health among Hispanics.
AB  - Hispanics are disproportionately affected by substance abuse, HIV infection,
      intimate partner violence, and mental health conditions. To address health
      disparities among Hispanics and other vulnerable groups, it is necessary to
      understand the complex interactions between health conditions clustering together
      (e.g., substance abuse, intimate partner violence, and HIV) and the social
      ecology in which these conditions exist. A syndemic orientation, a consideration
      of clustering epidemics and common individual, relationship, cultural, and
      socioenvironmental factors linking these conditions, may be helpful in developing
      comprehensive models that expand our ability to understand and address health
      disparities. The purpose of this paper is to introduce a Syndemic Model of
      Substance Abuse, Intimate Partner Violence, HIV Infection, and Mental Health
      among Hispanics, and provide evidence from the research literature to support the
      central relationships and risk and protective factors (i.e., potential links
      between conditions) depicted by the model. The development and evaluation of
      interventions aimed at the prevention of substance abuse, intimate partner
      violence, HIV/AIDS, and mental health problems as a syndemic affecting Hispanics
      is urgently needed. Public health nurses can initiate this endeavor with the
      guidance of a Syndemic Model.

PMID- 21736616
TI  - Public health nursing: an autonomous career for World War II nurse veterans.
AB  - The 1944 G.I. Bill increased accessibility of higher education to male veterans.
      Less is known about how its availability affected opportunities for female
      veterans. The purpose of this study was to examine nurse veterans' use of the G.
      I. Bill at one large public university. Primary sources included archival
      documents of one large public university as well as articles published in
      professional nursing and medical journals of the 1940s and 1950s. Secondary
      sources addressing nursing and nursing education history, and the history of the
      G. I. Bill provided further context. Historical research methodology was
      conducted. Findings demonstrate that nurse veterans desired more independence in
      practice following the war. Archival documents of one large public university
      show that nurse veterans used G. I. Bill funds to seek degrees in public health
      nursing. The specialty of public health provided increased independence and
      autonomy of practice not experienced in hospital based care. G.I. Bill
      educational funds provided these nurse veterans the means to attain degrees in
      public health nursing, providing them the opportunity for more autonomous
      practice.

PMID- 21736617
TI  - Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related
      orphan receptor.
AB  - Melatonin modulates a wide array of physiological events with pleiotropic effects
      on the immune system. While the relevance of specific melatonin membrane
      receptors has been well established for several biological functions, retinoic
      acid-related orphan receptor alpha (RORalpha) has been suggested as a mediator of
      nuclear melatonin signalling by results obtained from pharmacological approaches.
      However, a melatonin-mediated downstream effect cannot be ruled out, and further
      evidence is needed to support a direct interaction between melatonin and
      RORalpha. Here, we show that RORalpha is mainly located in human Jurkat T-cell
      nucleus, and it is co-immunoprecipitated with melatonin. Moreover,
      immunocytochemistry studies confirmed the co-localization of melatonin and
      RORalpha. Melatonin promoted a time-dependent decrease in nuclear RORalpha
      levels, suggesting a role in the RORalpha transcriptional activity.
      Interestingly, RORalpha acts as a molecular switch implicated in the mutually
      exclusive generation of Th17 and Treg cells, both involved in the harm/protection
      balance of immune conditions such as autoimmunity or acute transplant rejection.
      Therefore, the identification of melatonin as a natural modulator of RORalpha
      gives it a tremendous therapeutic potential for a variety of clinical disorders.

PMID- 21736618
TI  - Bilateral crystalline lens dislocation associated with dilated cardiomyopathy in
      a patient with underlying hyperhomocysteinaemia.

PMID- 21736619
TI  - Severe combined immunodeficiency in a Caspian filly.

PMID- 21736620
TI  - Reversible encephalopathy secondary to thiamine deficiency in 3 cats ingesting
      commercial diets.

PMID- 21736621
TI  - Coagulation profiles of healthy Andalusian donkeys are different than those of
      healthy horses.
AB  - BACKGROUND: Coagulation disorders are frequently diagnosed, especially in
      hospitalized equidae, and result in increased morbidity and mortality. However,
      hemostatic reference intervals have not been established for donkeys yet.
      OBJECTIVES: To determine whether the most common coagulation parameters used in
      equine practice are different between healthy donkeys and horses. ANIMALS: Thirty
      eight healthy donkeys and 29 healthy horses. METHODS: Blood samples were
      collected to assess both coagulation and fibrinolytic systems by determination of
      platelet count, fibrinogen concentration, clotting times (prothrombin time [PT]
      and activated partial thromboplastin time [aPTT]), fibrin degradation products
      (FDP) and D-Dimer concentrations. RESULTS: PT and aPTT in donkeys were
      significantly (P < .05) shorter than those of horses. In contrast, FDP and D
      Dimer concentrations were significantly (P < .05) higher in donkeys than in
      horses. CONCLUSIONS AND CLINICAL IMPORTANCE: The coagulation parameters most
      commonly determined in equine practice are different in donkeys compared with
      horses. Thus, the use of normal reference ranges reported previously for healthy
      horses in donkeys might lead to a misdiagnosis of coagulopathy in healthy
      donkeys, and unnecessary treatments in sick donkeys. This is the first report of
      normal coagulation profile results in donkeys, and further studies are warranted
      to elucidate the physiological mechanisms of the differences observed between
      donkeys and horses.

PMID- 21736622
TI  - Prevalence of hypertrophic cardiomyopathy in a cohort of British Shorthair cats
      in Denmark.
AB  - BACKGROUND: Familial hypertrophic cardiomyopathy (HCM) has been described
      previously in British Shorthair cats (BSH), but until now, no reports have been
      published describing the prevalence of the disease within this breed. OBJECTIVES:
      The aim of this study was to assess the prevalence of HCM in a large cohort of
      BSH and to evaluate the effect of sex, weight, and increasing age as potential
      risk factors for this disease. ANIMALS: Three hundred and twenty-nine BSH
      presented for routine HCM screening during a 4-year period. METHODS: Prospective
      cross-sectional study in which all cats were screened for HCM by conventional
      echocardiography. RESULTS: A total of 329 cats were examined, 214 females and 115
      males, with a median age of 2.3 years (range, 0.8-14.1). Twenty-eight cats (8.5%)
      were classified as HCM-positive, 14 (4.3%) as equivocal, 282 (85.7%) as HCM
      negative, and 5 (2.1%) were diagnosed with other cardiac diseases. The median age
      for diagnosis of HCM was 2.7 years (range, 0.9-14.1). Male cats had a
      significantly higher occurrence of HCM (20.4%) compared with the females (2.1%)
      corresponding to an odds ratio of 7.89 (95 % CI, 2.54-28.08) for males versus
      females adjusted for age and weight (P < .001). CONCLUSION: The BSH in our cohort
      had a high prevalence of HCM, often of early onset and with a significant male
      sex predisposition. We strongly recommend echocardiographic screening in this
      breed, especially cats used for breeding.

PMID- 21736623
TI  - An open-label, dose-escalating phase I study of elsamitrucin (SPI 28090) in
      treatment of malignant solid tumors in dogs.
AB  - BACKGROUND: Elsamitrucin, the most potent topoisomerase II inhibitor available,
      is unique in that it does not cause neutropenia or cardiotoxicosis. It has
      antitumor activity in human patients with relapsed or refractory non-Hodgkin's
      lymphoma. OBJECTIVES: To determine the maximum tolerated dose (MTD), safety, and
      toxicity of elsamitrucin when administered to tumor-bearing dogs and to evaluate
      the incidence and severity of adverse events. ANIMALS: Twenty client-owned dogs
      with spontaneous malignant solid tumors or lymphoma that were refractory to, or
      for which the owner declined, conventional therapy were enrolled. METHODS:
      Prospective, open-label, single-agent study. Escalating doses of elsamitrucin
      were administered once weekly i.v. for up to 16 weeks in a modified 3 + 3 Phase I
      design. The starting dose was 0.06 mg/kg with escalation to 0.08 and 0.09 mg/kg.
      Dogs that remained on the study were monitored for evidence of toxicoses for at
      least 4 weeks and for survival every 2 months. RESULTS: Serious adverse events
      (SAEs) possibly attributable to elsamitrucin include: 1 dog developed heart
      failure and another developed hepatotoxicosis manifested by increased alanine
      aminotransferase, alkaline phosphatase, and total bilirubin (0.06 mg/kg dose); 1
      dog developed severe anorexia and diarrhea, another developed severe diarrhea
      alone, and a 3rd dog went into cardiac arrest (0.09 mg/kg dose). A dose of 0.08
      mg/kg was well tolerated with no SAEs. CONCLUSIONS AND CLINICAL IMPORTANCE: The
      MTD and recommended dose for Phase II trials of elsamitrucin is 0.08 mg/kg i.v.
      weekly. Elsamitrucin might be considered for combination protocols with
      myelosuppressive chemotherapy agents.

PMID- 21736624
TI  - Low-dose cyclophosphamide selectively decreases regulatory T cells and inhibits
      angiogenesis in dogs with soft tissue sarcoma.
AB  - BACKGROUND: Low-dose, continuous (metronomic) chemotherapy improves tumor control
      by inhibiting tumor angiogenesis and suppressing regulatory T cells (Treg) in
      mice and humans. The effects of metronomic chemotherapy on Treg and tumor
      angiogenesis in dogs has not been investigated previously. OBJECTIVE: To
      determine whether metronomic cyclophosphamide (CYC) therapy decreases Treg or
      exhibits antiangiogenic activity or both in dogs with soft tissue sarcoma (STS).
      We hypothesized that Treg numbers would be increased in dogs with STS and that
      continuous dosing of CYC would decrease Treg in a dose-dependent manner, as well
      as exhibit antiangiogenic activity. ANIMALS: Eleven client-owned dogs with grade
      I or II STS. Twenty-one healthy dogs were used as controls. METHODS: Prospective,
      open, clinical trial. Dogs with STS were enrolled in 2 dose cohorts and
      administered CYC at 12.5 or 15 mg/m(2) p.o. once daily for 28 days. Whole blood
      and tumor biopsy specimens were obtained on days 0, 14, and 28 to assess changes
      in T lymphocyte subsets by flow cytometry and tumor microvessel density (MVD),
      respectively. RESULTS: Administration of CYC at 12.5 mg/m(2)/d significantly
      decreased the number of Treg from days 0 to 28, but there was no change in the
      percentage of Treg or tumor MVD. In dogs that received CYC at 15.0 mg/m(2)/d,
      both the number and percent of Treg as well as tumor MVD were significantly
      decreased over 28 days. CONCLUSIONS: CYC administered at 15 mg/m(2)/d should be
      used in further studies examining the antitumor properties of low-dose CYC in
      dogs.

PMID- 21736625
TI  - Interleukin-2, interleukin-6 and T regulatory cells in peripheral blood of
      patients with Behcet's disease and recurrent aphthous ulcerations.
AB  - BACKGROUND: One of the factors involved in the pathogenesis of Behcet disease
      (BD) and recurrent aphthous ulcerations (RAU) is a cell-mediated immune response
      in which several cytokines (interleukin-2, interleukin-6) and T regulatory cell
      (T reg cell) population seem to play a major role. The aim of this study was to
      measured the interleukin-2 (IL-2), interleukin-6 (IL-6) levels and analysis of
      CD4(+) CD25(+) Foxp-3(+) Treg cells in peripheral blood from patients with BD and
      RAU. In addition; we also analysed peripheral blood from healthy subjects for
      comparison. METHODS: Thirty patients (15 men and 15 women) with BD, 30 patients
      (12 men and 18 women) with RAU and 15 healthy control subjects (nine men and six
      women) participated in the study. Analysis of CD4(+) CD25(+) Foxp-3(+) Treg
      cells, IL-2 and IL-6 levels have been measured in flow cytometry. RESULTS: No
      statistical differences were observed in the serum levels of IL-2 and IL-6
      between BD and RAU patients, and healthy subjects. Although there were no
      statistical differences in the number of CD4(+) CD25(+) Foxp-3(+) cells between
      groups, there were statistically significant differences in the number of CD4(+)
      CD25(bright) Treg cells. CD4(+) CD25(bright) Treg cells were significantly
      increased in BD and RAU patients compared to healthy subjects. Statistical
      analysis revealed no difference according to the number of CD4(+) CD25(bright)
      cells between BD and RAU patients. CONCLUSIONS: These results indicate that
      CD4(+) CD25(bright) T regulatory cells may be contributing factor in the
      pathogenesis of BD and RAU.

PMID- 21736626
TI  - Total serum tryptase levels are higher in young infants.
AB  - BACKGROUND: Mast cells participate in immune defense and allergic disease. At
      baseline, serum tryptase levels primarily reflect mast cell burden, while mast
      cell degranulation leads to granule tryptase release, which may be detectable as
      a transitory elevation of serum tryptase levels. Thus, mast cell burden and mast
      cell activity are reflected by serum tryptase levels, but reports are scarce in
      infants under 1 yr. We aimed at defining levels of total serum tryptase levels in
      this population. METHODS: Total serum tryptase levels (ImmunoCAP; Phadia) were
      measured in 372 sera from infants younger than 1 yr. Two hundred and forty-two
      sera came from non-atopic, non-allergic infants in good condition, who had blood
      drawn for routine follow-up or diagnosis of illnesses that are not known to
      induce changes in serum tryptase levels. Seventy-two sera were from atopic and/or
      allergic infants, and 58 sera were from non-atopic, non-allergic infants
      requiring intensive care. RESULTS: Median serum tryptase levels were highest in
      infant2s under 3 months (6.12 +/- 3.47 MUg/l) and gradually decreased before
      reaching levels similar to those described in adults and older children (3.85 +/-
      1.8 MUg/l between 9 and 12 months). Atopic/allergic status was associated with
      even higher tryptase levels (14.20 +/- 10.22 MUg/l in infants younger than 3
      months). Intensive care patients had lower levels of serum tryptase (4.12 +/-
      3.38 MUg/l in infants younger than 3 months). Longitudinal follow-up was
      performed in 27 patients and showed tryptase levels decrease over time in
      individual patients. Infants'sex was not found to interfere with serum tryptase
      levels. CONCLUSION: Total serum tryptase levels are significantly higher in
      younger infants compared with older ones. In infants of the same age, serum
      tryptase levels may vary according to the clinical condition and thus suggest
      mast cell involvement in the physiologic as well as in the allergic immune
      responses of young infants.

PMID- 21736628
TI  - Primary invasive squamous cell carcinoma of male bulbar urethra completely
      responded to concurrent chemoradiation therapy.

PMID- 21736629
TI  - Black yeast-like fungi in skin and nail: it probably matters.
AB  - Black yeast-like fungi are rarely reported from superficial infections. We
      noticed a consistent prevalence of these organisms as single isolations from
      mycological routine specimens. To investigate the prevalence of black yeast-like
      fungi in skin, hair and nail specimens and to discuss the probability of these
      species to be involved in disease. Slow-growing black yeast-like fungi in routine
      specimens were prospectively collected and identified. A questionnaire regarding
      patient information was sent to physicians regarding black yeast-like fungus
      positive patients. A total of 20,746 dermatological specimens were examined by
      culture. Black yeast-like fungi accounted for 2.2% (n=108) of the positive
      cultures. Only 31.0% of the samples, culture positive for black yeast-like fungi
      were direct microscopy positive when compared with overall 68.8% of the culture
      positive specimens. The most prevalent species were Phialophora europaea (n=29),
      Coniosporium epidermidis (n=12), Ochroconis cf. humicola (n=6) and
      Cladophialophora boppii (n=4). These are not common saprobes and thus less likely
      to be coincidental colonizers. In 10/30 cases, discolouration of nail/skin had
      been noticed. A limited number of black yeast-like fungi were repeatedly isolated
      from routine specimens suggesting that they may play a role in superficial
      infections or as colonizers.

PMID- 21736630
TI  - Post-trauma primary cutaneous cryptococcosis in an immunocompetent host by
      Cryptococcus gattii VGII.

PMID- 21736631
TI  - Ethmoido-maxillary sinusitis caused by the basidiomycetous fungus Schizophyllum
      commune.

PMID- 21736632
TI  - Pyrosequencing of a hypervariable region in the internal transcribed spacer 2 to
      identify clinical yeast isolates.
AB  - The incidence of invasive fungal infection has increased significantly. A
      majority of the infections is caused by yeast. Clinically important yeast show
      species-specific differences in susceptibility to antifungal agents therefore
      rapid and accurate identification of the pathogen is essential. We aimed to
      validate pyrosequencing of 40 nucleotides in the internal transcribed spacer 2
      (ITS2) for species identification of yeast. Amplification of ITS2 and
      pyrosequencing of targeted region were performed in 940 clinical isolates of
      yeast. A local database containing the 40 nucleotide ITS2 sequences of 33 species
      of medically important yeast was generated using published sequences of type
      strains. The sequencing results were searched against the local database using
      the BLAST algorithm to identify the species of yeast. The length of sequences
      obtained from pyrosequencing averaged between 40-61 nucleotides. Pyrosequencing
      identified 940 clinical isolates of yeast down to 14 species level, whereby 931
      isolates belonged to genus Candida (11 species), four of Saccharomyces
      cerevisiae, three of Malassezia pachydermatis and two of Rhodotorula
      mucilaginosa. In addition, intraspecies specific sequence variations in Candida
      albicans and Candida glabrata were detected. Pyrosequencing of 40 nucleotides in
      ITS2 is reliable for species identification of yeast. This methodology can
      contribute to the high quality management of patients with fungal infections.

PMID- 21736633
TI  - Two cases of reciprocal chromosomal translocation (4; 7)(p+; q-) (2; 8)(q-; q+)
      in piglets produced by ICSI.
AB  - In this study, the karyotypes of 14 piglets from four different litters produced
      by intracytoplasmic sperm injection (ICSI) and embryo transfer were analysed. The
      chromosome analysis was based on a classical cytogenetic examination following
      the standard protocols of lymphocyte cultures. Two cases of reciprocal
      translocation [(4; 7)(p+; q-) and (2; 8)(q-; q+)] were detected in two female
      transgenic piglets. These animals showed neither anatomical nor physiological
      alterations and had normal growth. To our knowledge, this is the first karyotype
      study of piglets produced by ICSI.

PMID- 21736634
TI  - Bilateral epididymal sperm granulomas following urethrostomy in a German shepherd
      dog.
AB  - Bilateral enlargement of both epididymes was observed in a 6-year-old German
      shepherd dog following a pre-scrotal urethrostomy. Testicular parenchyma showed
      regular structure, and the spermatogenesis and the steroidogenic functions were
      not modified. However, macroscopic examination of the tail and the body of both
      epididymes exhibited multiple white and well-delimited foci. Histopathological
      study of the epididymes confirmed the development of granulomas associated with
      extravasated spermatozoa. Urethrostomy caused a severe stenosis of the penile
      urethra, favouring the retention of urine at the urinary bladder. The retrograde
      pressure exerted by the distension of the urinary bladder could have allowed the
      urine to reach the prostatic urethra and the deferent ducts and, finally, the
      epididymes, causing irritation and rupture of the mucous layer of the epididymal
      duct, the consequent sperm extravasation and the development of sperm granulomas.
      We speculate that the inadequate surgical resolution of the urethral calculi
      caused the bladder distension, the subsequent retrograde flow of urine and the
      development of the lesions.

PMID- 21736635
TI  - Epidemiology and impact of Neospora caninum infection in three Queensland
      tropical dairy herds.
AB  - This study investigated the epidemiology of Neospora caninum in three tropical
      dairy herds in North Queensland, Australia. All animals in the herds were bled,
      and the sera were tested by ELISA for N. caninum antibodies. Herd records were
      examined, and the number of calves carried to term and the number of abortions
      which occurred over the lifetime of each animal were recorded to determine the
      abortion rate for each animal. Pedigrees were constructed for two of the herds to
      investigate whether vertical transmission was occurring. The seroprevalence of N.
      caninum ranged from 23% to 34%. The abortion rate in seropositive animals was
      significantly (p < 0.001) higher than in seronegative animals in all three herds
      (12-20.1% cf. 3.6-7%). Overall, the probability of a calf being seropositive was
      3.5 times higher when the dam was also seropositive than when the dam was
      seronegative. Subsequent selective breeding employed by one herd reduced the N.
      caninum seroprevalence from 23% to 5% over a 9-year period. This study shows that
      N. caninum infection is prevalent in North Queensland dairy cattle, and both post
      natal infection and vertical transmission are common.

PMID- 21736636
TI  - Partial foetal retention following aglepristone treatment in a bitch.
AB  - This short communication describes the case of partial foetal retention in an 18
      month-old female French bulldog following induction of abortion owing to an
      undesired mating. Abortion was induced with aglepristone administered in two
      consecutive protocols of a dual injection 1 day apart. After failure of the first
      treatment to achieve abortion, 15 days later, a second treatment was
      administered. Delivering of aborted foetus occurred 2 days after the last
      administration. Five weeks after the abortion, the female showed a weak
      haemorrhagic vaginal discharge. On ultrasound examination, the presence of
      uterine wall distension as well as a puppy skull inside the uterus was observed.
      This clinical case makes clear that although aglepristone is a very reliable
      drug, follow-up of the female during treatment and in the immediate post-partum
      is necessary to ensure a good outcome.

PMID- 21736637
TI  - Adding ascorbic acid to vitrification and IVC medium influences preantral
      follicle morphology, but not viability.
AB  - In this study, we analysed the effect on morphology and viability of ovine
      primordial follicles, when ascorbic acid (AA) was added to vitrification and in
      vitro culture (IVC) media. For morphological analysis, ovarian tissue was
      vitrified using DMSO or ethylene glycol (EG), to which AA was added or omitted.
      After warming, the tissue was fixed for histology or 1-day cultured in the
      presence or absence of AA. Isolated primordial follicles from ovine ovarian
      tissue vitrified with DMSO or EG, both supplemented with AA were stained with
      trypan blue for viability analysis, or 5-day cultured with or without AA followed
      by a viability analysis. In this study, we report on the successful vitrification
      protocol developed for ovine ovarian tissue using EG. Vitrification using DMSO
      reduced the percentage of morphological normal primordial follicles, whereas
      addition of AA to the vitrification and culture media did enhance these results
      (p < 0.05). However, vitrification in a DMSO + AA medium followed by 5-day IVC
      resulted in a significant decrease in the follicular viability, independently of
      the presence of AA in the IVC medium.

PMID- 21736638
TI  - Two atypical cases of granulosa cell tumours in Belgian Blue heifers.
AB  - This paper describes two atypical cases of granulosa cell tumours (GCTs) in
      Belgian Blue heifers. In the first case, an 18-month-old heifer died after
      ovariectomy, and a granulosa-theca cell tumour was diagnosed post-mortem. The
      second heifer (31 months of age) was near term and was successfully treated
      surgically for a malignant granulosa cell tumour. Unfortunately, no further
      reproductive data are available, as the heifer was sold for slaughter. This is
      the first report describing GCTs in Belgian Blue beef cattle.

PMID- 21736639
TI  - DegU-phosphate activates expression of the anti-sigma factor FlgM in Bacillus
      subtilis.
AB  - The bacterial flagellum is a complex molecular machine that is assembled by more
      than 30 proteins and is rotated to propel cells either through liquids or over
      solid surfaces. Flagellar gene expression is extensively regulated to co-ordinate
      flagellar assembly in both space and time. In Bacillus subtilis, the proteins of
      unknown function, SwrA and SwrB, and the alternative sigma factor sigma(D) are
      required to activate expression of the flagellar filament protein, flagellin.
      Here we determine that in the absence of SwrA and SwrB, the phosphorylated form
      of the response regulator DegU inhibits sigma(D) -dependent gene expression
      indirectly by binding to the P(flgM) promoter region and activating expression of
      the anti-sigma factor FlgM. We further demonstrate that DegU-P-dependent
      activation of FlgM is essential to inhibit flagellin expression when flagellar
      basal body assembly is disrupted. Regulation of FlgM is poorly understood outside
      of Salmonella, and differential control of FlgM expression may be a common means
      of coupling flagellin expression to flagellar assembly.

PMID- 21736640
TI  - Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential
      ligand-binding properties and mediates biofilm formation.
AB  - The streptococcal antigen I/II (AgI/II)-family polypeptides are cell wall
      anchored adhesins expressed by most indigenous oral streptococci. Proteins
      sharing 30-40% overall amino acid sequence similarities with AgI/II-family
      proteins are also expressed by Streptococcus pyogenes. The S. pyogenes
      M28_Spy1325 polypeptide (designated AspA) displays an AgI/II primary structure,
      with alanine-rich (A) and proline-rich (P) repeats flanking a V region that is
      projected distal from the cell. In this study it is shown that AspA from serotype
      M28 S. pyogenes, when expressed on surrogate host Lactococcus lactis, confers
      binding to immobilized salivary agglutinin gp-340. This binding was blocked by
      antibodies to the AspA-VP region. In contrast, the N-terminal region of AspA was
      deficient in binding fluid-phase gp-340, and L. lactis cells expressing AspA were
      not agglutinated by gp-340. Deletion of the aspA gene from two different M28
      strains of S. pyogenes abrogated their abilities to form biofilms on saliva
      coated surfaces. In each mutant strain, biofilm formation was restored by trans
      complementation of the aspA deletion. In addition, expression of AspA protein on
      the surface of L. lactis conferred biofilm-forming ability. Taken collectively,
      the results provide evidence that AspA is a biofilm-associated adhesin that may
      function in host colonization by S. pyogenes.

PMID- 21736641
TI  - The dgt gene of Escherichia coli facilitates thymine utilization in thymine
      requiring strains.
AB  - The Escherichia coli dGTP triphosphohydrolase (dGTPase) encoded by the dgt gene
      catalyses the hydrolysis of dGTP to deoxyguanosine and triphosphate. The recent
      discovery of a mutator effect associated with deletion of dgt indicated
      participation of the triphosphohydrolase in preventing mutagenesis. Here, we have
      investigated the possible involvement of dgt in facilitating thymine utilization
      through its ability to provide intracellular deoxyguanosine, which is readily
      converted by the DeoD phosphorylase to deoxyribose-1-phosphate, the critical
      intermediate that enables uptake and utilization of thymine. Indeed, we observed
      that the minimal amount of thymine required for growth of thymine-requiring
      (thyA) strains decreased with increased expression level of the dgt gene. As
      expected, this dgt-mediated effect was dependent on the DeoD purine nucleoside
      phosphorylase. We also observed that thyA strains experience growth difficulties
      upon nutritional shift-up and that the dgt gene facilitates adaptation to the new
      growth conditions. Blockage of the alternative yjjG (dUMP phosphatase) pathway
      for deoxyribose-1-phosphate generation greatly exacerbated the severity of
      thymine starvation in enriched media, and under these conditions the dgt pathway
      becomes crucial in protecting the cells against thymineless death. Overall, our
      results suggest that the dgt-dependent pathway for deoxyribose-1-phosphate
      generation may operate under various cell conditions to provide deoxyribosyl
      donors.

PMID- 21736642
TI  - The cop operon is required for copper homeostasis and contributes to virulence in
      Streptococcus pneumoniae.
AB  - High levels of copper are toxic and therefore bacteria must limit free
      intracellular levels to prevent cellular damage. In this study, we show that a
      number of pneumococcal genes are differentially regulated by copper, including an
      operon encoding a CopY regulator, a protein of unknown function (CupA) and a P1
      type ATPase, CopA, which is conserved in all sequenced Streptococcus pneumoniae
      strains. Transcriptional analysis demonstrated that the cop operon is induced by
      copper in vitro, repressed by the addition of zinc and is autoregulated by the
      copper-responsive CopY repressor protein. We also demonstrate that the CopA
      ATPase is a major pneumococcal copper resistance mechanism and provide the first
      evidence that the CupA protein plays a role in copper resistance. Our results
      also show that copper homeostasis is important for pneumococcal virulence as the
      expression of the cop operon is induced in the lungs and nasopharynx of
      intranasally infected mice, and a copA(-) mutant strain, which had decreased
      growth in high levels of copper in vitro, showed reduced virulence in a mouse
      model of pneumococcal pneumonia. Furthermore, using the copA(-) mutant we
      observed for the first time in any bacteria that copper homeostasis also appears
      to be required for survival in the nasopharynx.

PMID- 21736643
TI  - Biochemical and genetic characterization of the three metabolic routes in
      Thermococcus kodakarensis linking glyceraldehyde 3-phosphate and 3
      phosphoglycerate.
AB  - In the classical Embden-Meyerhof (EM) pathway for glycolysis, the conversion
      between glyceraldehyde 3-phosphate (GAP) and 3-phosphoglycerate (3-PGA) is
      reversibly catalysed by phosphorylating GAP dehydrogenase (GAPDH) and
      phosphoglycerate kinase (PGK). In the Euryarchaeota Thermococcus kodakarensis and
      Pyrococcus furiosus, an additional gene encoding GAP:ferredoxin oxidoreductase
      (GAPOR) and a gene similar to non-phosphorylating GAP dehydrogenase (GAPN) are
      present. In order to determine the physiological roles of the three routes that
      link GAP and 3-PGA, we individually disrupted the GAPOR, GAPN, GAPDH and PGK
      genes (gor, gapN, gapDH and pgk respectively) of T. kodakarensis. The Deltagor
      strain displayed no growth under glycolytic conditions, confirming its proposed
      function to generate reduced ferredoxin for energy generation in glycolysis.
      Surprisingly, DeltagapN cells also did not grow under glycolytic conditions,
      suggesting that GAPN plays a key role in providing NADPH under these conditions.
      Disruption of gor and gapN had no effect on gluconeogenic growth. Growth
      experiments with the DeltagapDH and Deltapgk strains indicated that, unlike their
      counterparts in the classical EM pathway, GAPDH/PGK play a major role only in
      gluconeogenesis. Biochemical analyses indicated that T. kodakarensis GAPN did not
      recognize aldehyde substrates other than d-GAP, preferred NADP(+) as cofactor and
      was dramatically activated with glucose 1-phosphate.

PMID- 21736644
TI  - Body cavity fluid can induce epithelial and mesothelial differentiation from CD34
      positive peripheral blood stem cells in vitro.
AB  - OBJECTIVE: Primary culture of CD34 positive stem cells collected from human
      peripheral blood was performed with and without supplementation with concentrated
      ascitic fluid; morphological and immunocytochemical pictures of cultured cells
      were taken chronologically and compared. METHODS: CD34-positive stem cells
      collected from peripheral blood were cultured for 1, 24 and 48 hours.
      Concentrated ascitic fluid was added to the plates for the 24-and 48-hour
      cultures. For immunocytochemical studies, CD34, AE1/AE3, Ber-Ep4 (EA), EMA, EGFR,
      CD31, CA125 and D2-40 monoclonal antibodies were used. RESULTS: After culture,
      small round cells with naked nuclei began to enlarge and to exhibit various
      changes in the cytoplasm and nucleus. Supplementation with concentrated body
      cavity fluid enhanced these changes. CD34-positive cells with small round cell
      features were detected 1 hour after culture and these had no epithelial or
      mesothelial markers. After 24 hours, CD34-positive cells had disappeared and
      cells weakly positive for EGFR, EMA, CA125 and D2-40 were detected. Cells with
      strong and moderate positive reactions for EGFR, AE1/AE3, EA, EMA, D2-40 and
      CA125 were detected after 48 hours. Supplementation with concentrated body cavity
      fluid increased the intensity and number of positive cells for these markers
      compared with the control group. The positive reaction, not only for the
      epithelial markers such as EGFR and AE1/AE3, but also for mesothelial markers
      such as CA125 and D2-40, was found to be increased in small numbers of cells in
      direct proportion to the duration of the primary culture of the peripheral blood
      cells. CD31, characteristically expressed in endothelial cells, was negative in
      the cultured cells. CONCLUSION: Supplementation of peripheral blood CD34-positive
      stem cells with body cavity fluid in vitro enhanced their differentiation toward
      cells of an epithelial or mesothelial phenotype, concomitant with loss of
      immunoreactivity for CD34. It is assumed that the routine cytological observation
      of cells obtained from body cavity fluid might cause possible cytomorphological
      and immunophenotypical changes due to the action of the growth factors contained
      in the body cavity fluid.

PMID- 21736645
TI  - Intraperitoneal free cancer cells in non-gynaecological adenocarcinomas: a
      reproducibility study.
AB  - OBJECTIVE: In recent years, therapeutic approaches including cytoreductive
      surgery followed by intraperitoneal chemotherapy have proven effective in
      peritoneal carcinomatosis of colorectal origin. If cytology is to be used to
      include patients in aggressive treatment regimens, it is necessary to evaluate
      its performance, particularly in terms of specificity. The aim of this study was
      to assess interobserver agreement for the detection of intraperitoneal free
      cancer cells (IFCCs) in patients with non-gynaecological adenocarcinomas.
      METHODS: Over a 5-year period, 1223 patients were recruited in 19 French surgery
      departments. Peritoneal samples were examined in 14 dispersed pathology
      laboratories. Giemsa-stained slides were sent to a control reader blind to the
      previous diagnosis. Discordant cases, concordant positive results and a random
      selection of negative concordant cases were reviewed by a panel of seven
      cytopathologists. The 'final diagnosis' was that of the consensus meetings but
      took into account locally-processed slides. RESULTS: Gathering dubious cases with
      negative results, a 95.6% concordance was achieved between local readers and the
      control reader. IFCCs were ascertained by the panel in 85 cases (7.0%). Eight of
      873 colorectal cancers cases viewed locally were falsely positive (0.9%).
      Radiotherapy and neoadjuvant therapy had no impact on the false-positive rate as
      assessed by final validation by the panel (P > 0.05). Samples initially
      considered as dubious were reclassified as negative by the panel in 24 of 25
      cases (96.0%). CONCLUSIONS: The panel consensus allowed reclassification of most
      dubious/equivocal peritoneal cytology cases, whereas clearcut distinction between
      benign and malignant cases was correctly achieved in almost all cases.

PMID- 21736646
TI  - Effects of Trypanosoma cruzi infection on myocardial morphology, single
      cardiomyocyte contractile function and exercise tolerance in rats.
AB  - The aim of this study was to investigate the effects of Trypanosoma cruzi (T.
      cruzi) infection on myocardial morphology, single cardiomyocyte contractile
      function and exercise tolerance in rats. Adult Wistar rats were randomized into
      control (n = 14) and infected (n = 14) groups. Infected animals were inoculated
      with T. cruzi Y strain (300,000 trypomastigotes/50 g body weight). After 9 weeks,
      the animals were subjected to a treadmill running protocol. Then, the right
      atrium (RA) and left ventricle (LV) were removed for morphological and cell
      contractile evaluation. The infected animals exhibited a significant reduction in
      distance travelled, total time to fatigue and workload. In addition, these
      animals had hypertrophy, increased myocardial cellularity, and an increase in the
      proportion of collagen and blood vessels. RA and LV myocytes from infected
      animals showed marked contractile dysfunction under basal conditions and a
      reduced contractile response to beta-adrenergic stimulation. The workload of
      infected animals was correlated closely with the amplitude of cell shortening of
      RA and LV myocytes. T. cruzi infection influenced the myocardial morphology and
      the mechanical properties of RA and LV single myocytes negatively and reduced
      exercise tolerance. Single cardiomyocyte contractile dysfunction could constitute
      an additional mechanism of cardiac impairment and reduced exercise tolerance in
      this infection.

PMID- 21736647
TI  - T-DNA as a gene tag.
AB  - The characteristics of Agrobacterium-mediated plant transformation are such that
      the T-DNA can be used as an insertional mutagen and, by extension, a gene tag. An
      increasing number of mutants have been obtained as a result of T-DNA insertion
      and the versatility of this experimental system can be exploited further to tag
      sequences of DNA which control gene expression. While the isolation of specific
      mutations by T-DNA tagging in the past has been fortuitous, T-DNA-based vectors
      have the potential to generate transgenic plants with specific, selectable
      mutations.

PMID- 21736648
TI  - Identification and molecular mapping of a single Arabidopsis thaliana locus
      determining resistance to a phytopathogenic Pseudomonas syringae isolate.
AB  - We present a model pathosystem to dissect genetically the disease resistance
      response of plants against phytopathogenic bacteria. The interaction between
      Pseudomonas syringae pathovar maculicola (Psm) and Arabidopsis thaliana displays
      phenotypic varia-ion which depends on the genotype of both partners. Compatible
      interactions are defined by sustained in-planta bacterial growth and are normally
      accompanied of their appearance. For compatible interactions, resistance is
      defined by limited in-planta bacterial growth accompanied by a typical
      'hypersensitive response' (HR). We show that at least parts of this system fit
      the paradigms of Flor's 'gene-for-gene' hypothesis. We identify functionally a
      putative bacterial avirulence gene (avrRpm 1) from a Psm isolate which conditions
      the HR on A. thaliana ecotypes Oy-0 abd Col- 0, but not Nd-0. We also demonstrate
      that resistance to the Psm strain from which avrRpm1 was isolated segregates as a
      single trait in the crosses Col-o x Nd-0 and Nd-0 x Oy-0. Furthermore, we map
      this locus (RPM1) molecularly in the Col-0 x Nd-0 cross to a relatively small
      interval defined by two RFLP markers on A. thliana chromosome 3. Resistance in
      the second cross also maps to this locus and co-segregates with resistance to
      avrRpm1.

PMID- 21736649
TI  - Developmentally regulated epitopes of cell surface arabinogalactan proteins and
      their relation to root tissue pattern formation.
AB  - Two polymorphic forms of an extracellular arabinogalactan protein (AGP1 and
      AGP2), obtained from the conditioned media of two carrot suspension-cultured cell
      lines, have been identified in terms of binding of the anti-plasma membrane
      antibodies JIM4 and MAC207. AGP1 and AGP2 have been used as immunogens to
      generate further anti-AGP monoclonal antibodies. JIM14 identified an epitope
      carried by AGP2 and also by glycoproteins of low molecular weight localized to
      the plant cell wall. In addition, further antibodies (JIM13 and JIM15) identified
      carbohydrate epitopes of the AGPs that also occur on plasma membrane
      glycoproteins and are expressed by patterns of cells that reflect cell position
      at the carrot root apex. Indirect immunofluorescence microscopy indicated that
      JIM13 recognized the surface of cells forming the epidermis and cells marking the
      region and axis of the future xylem. JIM15 recognized a pattern of cells directly
      complementary to the JIM13 pattern. The panel of anti-AGP monoclonal antibodies
      now available indicates groups of cells within the root meristem that may reflect
      an early pre-pattern of the tissues of the mature root structure and suggests
      extensive modulation of cell surface AGPs during cell development and the
      positioning of cells within the apex.

PMID- 21736650
TI  - Characterization and expression profile of two UDP-glucosyltransferases, UGT85K4
      and UGT85K5, catalyzing the last step in cyanogenic glucoside biosynthesis in
      cassava.
AB  - Manihot esculenta (cassava) contains two cyanogenic glucosides, linamarin and
      lotaustralin, biosynthesized from l-valine and l-isoleucine, respectively. In
      this study, cDNAs encoding two uridine diphosphate glycosyltransferase (UGT)
      paralogs, assigned the names UGT85K4 and UGT85K5, have been isolated from
      cassava. The paralogs display 96% amino acid identity, and belong to a family
      containing cyanogenic glucoside-specific UGTs from Sorghum bicolor and Prunus
      dulcis. Recombinant UGT85K4 and UGT85K5 produced in Escherichia coli were able to
      glucosylate acetone cyanohydrin and 2-hydroxy-2-methylbutyronitrile, forming
      linamarin and lotaustralin. UGT85K4 and UGT85K5 show broad in vitro substrate
      specificity, as documented by their ability to glucosylate other hydroxynitriles,
      some flavonoids and simple alcohols. Immunolocalization studies indicated that
      UGT85K4 and UGT85K5 co-occur with CYP79D1/D2 and CYP71E7 paralogs, which catalyze
      earlier steps in cyanogenic glucoside synthesis in cassava. These enzymes are all
      found in mesophyll and xylem parenchyma cells in the first unfolded cassava leaf.
      In situ PCR showed that UGT85K4 and UGT85K5 are co-expressed with CYP79D1 and
      both CYP71E7 paralogs in the cortex, xylem and phloem parenchyma, and in specific
      cells in the endodermis of the petiole of the first unfolded leaf. Based on the
      data obtained, UGT85K4 and UGT85K5 are concluded to be the UGTs catalyzing in
      planta synthesis of cyanogenic glucosides. The localization of the biosynthetic
      enzymes suggests that cyanogenic glucosides may play a role in both defense
      reactions and in fine-tuning nitrogen assimilation in cassava.

PMID- 21736651
TI  - Differential contribution of EF-hands to the Ca2+-dependent activation in the
      plant two-pore channel TPC1.
AB  - Two-pore channels (TPC) have been established as components of calcium signalling
      networks in plants and animals. In plants, TPC1 in the vacuolar membrane is gated
      open upon binding of calcium in a voltage-dependent manner. Here, we analyzed the
      molecular mechanism of the Ca2+-dependent activity of TPC1 from Arabidopsis
      thaliana, using site-directed mutagenesis of its two canonical EF-hands. Wild
      type TPC1 and TPC1-D335A with a mutated first Ca2+ ligand in EF-hand 1 produced
      channels that retained their voltage- and Ca2+-dependent gating characteristics,
      but were less sensitive at Ca2+ concentrations < 200 MUm. Additional mutation of
      the first Ca2+ ligand in EF-hand 2 resulted in silent TPC1-D335A/D376A channels.
      Similarly, the single mutant TPC1-D376A could not be activated up to 1 mm Ca2+,
      indicating that the second EF-hand is essential for the Ca2+-dependent channel
      gating. Molecular modeling suggests that EF-hand 1 displays a low-affinity
      Ca2+/Mg2+-binding site, while EF-hand 2 represents a high-affinity Ca2+-binding
      site. Together, our data prove that EF-hand 2 is responsible for the Ca2+
      receptor characteristics of TPC1, while EF-hand 1 is a structural site required
      to enable channel responses at physiological changes in Ca2+ concentration.

PMID- 21736652
TI  - Endosomal signaling of the tomato leucine-rich repeat receptor-like protein
      LeEix2.
AB  - Extracellular leucine-rich repeat (LRR) receptor-like proteins (RLPs) represent a
      unique class of cell-surface receptors, as they lack a functional cytoplasmic
      domain. Our knowledge of how RLPs that do not contain a kinase or Toll domain
      function is very limited. The tomato RLP receptor LeEix2 signals to induce
      defense responses mediated by the fungal protein ethylene-inducing xylanase
      (EIX). The movement of FYVE-positive endosomes before and after EIX application
      was examined using spinning disc confocal microscopy. We found that while FYVE
      positive endosomes generally observe a random movement pattern, following EIX
      application a subpopulation of FYVE-positive endosomes follow a directional
      movement pattern. Further, cellular endosomes travel greater distances at higher
      speeds following EIX application. Time-course experiments conducted with specific
      inhibitors demonstrate the involvement of endosomal signaling in EIX-triggered
      defense responses. Abolishing the existence of endosomes or the endocytic event
      prevented EIX-induced signaling. Endocytosis/endosome inhibitors, such as
      Dynasore or 1-butanol, inhibit EIX-induced signaling. Moreover, treatment with
      Endosidin1, which inhibits an early step in plasma membrane/endosome trafficking,
      enhances the induction of defense responses by EIX. Our data indicate a distinct
      endosomal signaling mechanism for induction of defense responses in this RLP
      system.

PMID- 21736653
TI  - OsIAA23-mediated auxin signaling defines postembryonic maintenance of QC in rice.
AB  - Although the quiescent center (QC) is crucial to root development, the molecular
      mechanisms that regulate its postembryonic maintenance remain obscure. In this
      study, a semi-dominant mutant that exhibits pleiotropic defects in root tissues,
      which includes the root cap, lateral and crown roots, was isolated. The mutant is
      characterized by a loss of QC identity during postembryonic development, and the
      displayed defects result from a stabilizing mutation in domain II of OsIAA23
      (Os06g39590). Expression of OsIAA23 is specific to the QC of the root tip during
      the development of primary, lateral and crown roots. Consistent with OsIAA23
      expression in the QC, the auxin signaling marked by DR5p::GUS (beta
      glucuronidase) was absent in the QC region of Osiaa23. Transgenic rice plants
      harboring Osiaa23 under the control of the QHB promoter mimic partially the
      defects of Osiaa23. These results indicate that the maintenance of the QC is
      dependent on OsIAA23-mediated auxin signaling in the QC. These findings provide
      insight into Aux/IAA-based auxin signaling during postembryonic maintenance of
      the QC in plants.

PMID- 21736654
TI  - Changes in nursing practice: associations with responses to and coping with
      errors.
AB  - AIMS AND OBJECTIVE: To investigate emotional responses of nurses and perceived
      senior staff responses to errors, error-coping strategies used by nurses and how
      these are associated with constructive or defensive changes in nursing practice.
      BACKGROUND: Healthcare professionals have generally reported distressing
      emotional responses to errors and fear concerns about their consequences.
      However, errors can also be part of a developmental process, by offering
      opportunities for learning and leading to constructive changes in clinical
      practice. DESIGN: Prospective, correlational, multicentre study. METHODS: Five
      hundred and thirty-six structured questionnaires completed from nurses employed
      in various hospital departments were considered eligible for data extraction. The
      revised questionnaire used was evaluated for content validity. RESULTS: Data
      analysis indicated that positive perceived senior staff responses (p = 0.030),
      accepting error responsibility (p = 0.031) and seeking social support (p = 0.019)
      predicted constructive changes in nursing practice, while negative perceived
      senior staff responses (p = 0.040) and error escape-avoidance (p = 0.041)
      predicted defensive changes. CONCLUSIONS: Errors promote constructive changes in
      clinical practice when nurses are encouraged to use adaptive error-coping
      strategies within a supportive, non-blaming culture. RELEVANCE TO CLINICAL
      PRACTICE: These findings highlight the role of senior staff in the establishment
      of a supportive, trustful ward climate, so that nurses can learn from errors,
      prevent their recurrence and improve patient safety.

PMID- 21736655
TI  - Predictions of single-nucleotide polymorphism differentiation between two
      populations in terms of mutual information.
AB  - Mutual information (I) provides a robust measure of genetic differentiation for
      the purposes of estimating dispersal between populations. At present, however,
      there is little predictive theory for I. The growing importance in population
      biology of analyses of single-nucleotide and other single-feature polymorphisms
      (SFPs) is a potent reason for developing an analytic theory for I with respect to
      a single locus. This study represents a first step towards such a theory. We
      present theoretical predictions of I between two populations with respect to a
      single haploid biallelic locus. Dynamical and steady-state forecasts of I are
      derived from a Wright-Fisher model with symmetrical mutation between alleles and
      symmetrical dispersal between populations. Analytical predictions of a simple
      Taylor approximation to I are in good agreement with numerical simulations of I
      and with data on I from SFP analyses of dispersal experiments on Drosophila fly
      populations. The theory presented here also provides a basis for the future
      inclusion of selection effects and extension to multiallelic loci.

PMID- 21736656
TI  - Nocturnal and pause-dependent amplification of J wave in Brugada syndrome.

PMID- 21736657
TI  - Atrial electrical and structural changes associated with longstanding
      hypertension in humans: implications for the substrate for atrial fibrillation.
AB  - INTRODUCTION: Hypertension (HT) is the most common modifiable risk factor for
      atrial fibrillation (AF), yet little is known of the atrial effects of chronic HT
      in humans. We aimed to characterize the electrophysiologic (EP) and
      electroanatomic (EA) remodeling of the right atrium (RA) in patients with
      chronically treated systemic HT and left ventricular hypertrophy (LVH) without a
      history of AF. METHODS AND RESULTS: Twenty patients with (systolic BP 145 +/- 10
      mmHg) and without (BP 119 +/- 11 mmHg, P < 0.01) systemic HT underwent detailed
      conventional EP and EA voltage and activation mapping. We measured RA
      refractoriness at the coronary sinus and high septum at cycle lengths (CLs) 600
      and 450 ms, and RA conduction velocities, activation times, and voltages at a
      global and regional level at CLs 600 ms and 300 ms. HT was associated with
      slowing of global (73 +/- 17 cm/s vs 96 +/- 12 cm/s in controls, P < 0.01) and
      regional conduction velocity particularly in the posterior RA (70 +/- 17 cm/s vs
      96 +/- 12 cm/s in controls, P < 0.01) at the crista terminalis (fractionation and
      double potentials in HT 72%+/- 4 vs 43%+/- 23 in controls, P = 0.04). Mean RA
      voltage was similar between the 2 groups, however HT was associated with an
      increase in areas of low voltage (<0.5 mV; HT 13% vs controls 9%, P = 0.04).
      Sustained AF was induced in 30% HT patients and no controls. CONCLUSION:
      Chronically treated systemic HT with LVH is accompanied by atrial remodeling
      characterized by: (i) global conduction slowing, (ii) regional conduction delay
      particularly at the crista terminalis, and (iii) increased AF inducibility. These
      changes may in part be responsible for the increased propensity to AF associated
      with systemic HT.

PMID- 21736658
TI  - Imaging of scar in patients with ventricular arrhythmias of right ventricular
      origin: cardiac magnetic resonance versus electroanatomic mapping.
AB  - INTRODUCTION: Assessment of late gadolinium enhancement (LGE) at cardiac magnetic
      resonance is often used to detect scar in patients with arrhythmias of right
      ventricular (RV) origin. Recently, electroanatomic mapping (EAM) has been shown
      to reliably detect scars corresponding to different cardiomyopathic substrates.
      We compared LGE with EAM for the detection of scar in patients with arrhythmias
      of RV origin. METHODS AND RESULTS: Thirty-one patients with RV arrhythmias and
      biopsy-proven structural heart disease (18 ARVC and 13 myocarditis), and 5 with
      idiopathic RV outflow tract arrhythmias underwent LGE analysis and EAM with scar
      validation through EAM-guided endomyocardial biopsy. EAM scars were present in 23
      (64%) patients (all with structural heart disease), whereas LGE was present only
      in 12 (33%). In 2 cases, EAM provided a false-positive diagnosis of a small scar
      in the basal perivalvular area. LGE correctly diagnosed EAM scar in 48% of
      patients, resulting in high positive (92%) but low negative (50%) predictive
      values. The distribution of LGE was significantly associated with the
      distribution of EAM scars (P < 0.001 in the free wall, P = 0.003 in the outflow
      tract, and P = 0.023 in the posterior/inferior wall). Presence of LGE reflected a
      higher extension of EAM scars (34.4 +/- 16.5% vs 7.9 +/- 10.1% of the RV area, P
      < 0.001). At receiver operating characteristic (ROC) analysis, an extension of
      scar >=20% of the RV area was the best cut-off value to detect LGE (sensitivity
      83%, specificity 92%). Of note, LGE missed 10 of 11 (91%) patients with EAM scars
      <20% of RV area. CONCLUSIONS: LGE is significantly less sensitive than EAM in
      identifying RV cardiomyopathic substrates. Absence of LGE does not rule out the
      presence of small scars, and EAM with biopsy should be considered to increase the
      diagnostic yield.

PMID- 21736659
TI  - Relationship between complex fractionated electrograms (CFE) and dominant
      frequency (DF) sites and prospective assessment of adding DF-guided ablation to
      pulmonary vein isolation in persistent atrial fibrillation (AF).
AB  - BACKGROUND: Sites of high DF are potential targets for AF ablation, but it is
      unknown if addition of DF ablation can improve procedural outcome. OBJECTIVES: We
      sought to (1) examine the relationship between DF sites and complex fractionated
      electrograms (CFE) and (2) prospectively assess the long-term outcome of adding
      DF ablation to pulmonary vein antral isolation (PVAI) for persistent AF. METHODS:
      First, 20 patients with persistent AF who underwent previous CFE-guided ablation
      and who had AF terminate during ablation were studied retrospectively (group I).
      Bipolar, 8-second electrograms were collected by a circular catheter (288 +/- 86
      points/map). The EnSite NavX system allows for automated display of both CFE and
      DF maps. Electrograms with cycle length <120 ms were considered CFE and were
      compared to DF sites > 8 Hz (direct inverse relationship). Sites of AF
      termination were related to CFE and DF sites. Based on these observations, 30
      different patients (group II) with persistent AF prospectively underwent DF
      guided ablation plus PVAI. They were followed every 3 months for 1 year (visit,
      Holter, ECG). These patients were compared to case-matched controls undergoing
      PVAI alone (group III). RESULTS: In group I, there was a significant, inverse
      correlation between DF and CFE values at each point (r =-0.24, P < 0.001). DF
      surface area was less than CFE area (27 +/- 5 cm(2) vs 34 +/- 4 cm(2) , P =
      0.03). CFE sites overlapped 48 +/- 27% with the DF surface area. Nonoverlapping
      CFE sites were contiguous to DF sites. AF termination occurred where DF and CFE
      overlapped, and at these sites, DF was always greater than the mean DF for the
      map. In group II, all DF sites above the mean value were prospectively ablated
      during AF. AF termination was noted in only 2/30 (7%) patients. After DF
      ablation, PVAI was performed and termination increased to 4/30 patients (14%). At
      1 year, freedom from atrial arrhythmia > 30 seconds occurred in 57% of DF+PVAI
      compared to 60% in patients receiving PVAI alone (P = 0.18). CONCLUSIONS: DF and
      CFE regions overlap only about 50%. AF termination retrospectively occurred on
      overlapping CFE/DF sites where DF was above the mean. However, prospective
      ablation of DF sites plus PVAI resulted in low AF termination rates, and did not
      improve 1 year success over PVAI alone.

PMID- 21736660
TI  - Sinus rhythm ECG criteria associated with basal-lateral ventricular tachycardia
      substrate in patients with nonischemic cardiomyopathy.
AB  - INTRODUCTION: Patients with nonischemic cardiomyopathy (NICM) and ventricular
      tachycardia (VT) usually have basal-lateral scar in the left ventricle (LV). We
      sought to determine electrocardiogram (ECG) characteristics that may help
      identify NICM patients with basal-lateral scar and VT. METHODS AND RESULTS: Phase
      I, study patients (n = 25) had NICM, VT, and endocardial/epicardial basal-lateral
      LV low voltage consistent with scar on detailed mapping. ECGs were compared to
      controls (n = 18) with NICM, and comparable age and gender without VT/known scar.
      All patients had either sinus or paced atrial rhythm ECGs without bundle-branch
      block or ventricular pacing. In phase II, criteria were evaluated prospectively,
      blinded to clinical data, using ECGs from 15 NICM patients, of which 7 patients
      had VT and endocardial/epicardial basal-lateral LV scar on detailed mapping. Of
      ECG characteristics studied, V1 R and R:S ratio, and V6 S and S:R ratio were
      univariately associated with basal-lateral-scar associated VT. Controlling for
      LVEF and multicollinearity in multivariate analyses, V1 R >= 0.15 mV (P = 0.001)
      and V6 S >= 0.15 mV (P < 0.001), or V6 S:R >= 0.2 mV (P < 0.001), best predicted
      presence of basal-lateral scar. In Phase II, the former criteria best identified
      those with NICM and VT because of basal-lateral scar, with sensitivity and
      specificity 0.86 and 0.88, respectively. CONCLUSIONS: Among patients with NICM,
      VT, and normal QRS duration, V1 R >= 0.15 mV and V6 S >= 0.15 mV predicted
      presence of basal-lateral LV areas of bipolar low voltage. This ECG information
      may have important value in defining presence of LV scar and possible risk for VT
      in NICM patients. 

PMID- 21736661
TI  - The power of observation.
AB  - PROBLEM: In the golden age of evidence-based medicine, how should one view the
      cohort-controlled study of IVIG + anti-TNF-alpha (Humira) in recurrent in vitro
      fertilization (IVF) failure patients with an elevated Th1/Th2 cytokine production
      ratio. METHOD: Critical analysis of the nature of evidence for causation.
      RESULTS: A better delivery rate and a live birth rate per embryo approaching the
      estimated maximum possible in patients whose elevated Th1/Th2 ratio corrected to
      normal compared to those with an incomplete correction is a strong argument for
      causation. A maximal improvement when treatment was given 61-120 days before
      embryo transfer suggests a possible mechanism via improving the physiology during
      follicle development. CONCLUSION: Independent replication to verify results would
      augment power.

PMID- 21736662
TI  - High levels of maternal serum IL-17 and activin A in pregnant women affected by
      systemic lupus erythematosus.
AB  - PROBLEM: To evaluate changes of serum IL-17, activin A, follistatin, and other
      cytokines during pregnancy in women with systemic lupus erythematosus (SLE).
      METHOD OF STUDY: A group of patients with SLE and controls were longitudinally
      studied, collecting a blood sample before and during three trimesters of
      pregnancy. Serum activin A, follistatin, IL-17, IL-6, IL-10, and TNF-alpha
      concentrations were evaluated by specific ELISA. RESULTS: Before pregnancy, while
      serum IL-17, IL-6, IL-10, and TNF-alpha resulted significantly higher in women
      with SLE (P<0.001), activin A and follistatin were not changed. Serum IL-17
      concentrations were higher in SLE than in controls with no changes during
      pregnancy. IL-6 increased in both groups, resulting higher in SLE than in
      controls only in the first trimester (P<0.05). IL-10 concentration in SLE
      increased during pregnancy resulting significantly higher than in controls
      (P<0.01). TNF-alpha levels were higher in SLE than in controls in third trimester
      (P<0.01). Serum activin A levels in SLE were significantly higher than in
      controls (P<0.001) at third trimester. CONCLUSION: Women with SLE show increased
      secretions of activin A, IL-17, IL-6, IL-10, and TNF-alpha during gestation, with
      a different trend for the various cytokines. These data suggest that patients
      with SLE have a hyper-reactive immune system, probably receiving a placental
      contribution.

PMID- 21736663
TI  - Cardiac arrest upon induction of anesthesia in children with cardiomyopathy: an
      analysis of incidence and risk factors.
AB  - INTRODUCTION: It is thought that patients with cardiomyopathy have an increased
      risk of cardiac arrest on induction of anesthesia, but there is little available
      data. The purpose of this study was to identify the incidence and potential risk
      factors for cardiac arrest upon induction of anesthesia in children with
      cardiomyopathy in our institution. METHODS: A retrospective chart review was
      performed. Eligible patients included patients admitted between 1998 and 2008
      with the International Statistical Classification of Disease code for
      cardiomyopathy (ICD-9 code 425) who underwent airway intervention for sedation or
      general anesthesia in the operating room, cardiac diagnostic and interventional
      unit (CDIU) or intensive care unit. Patients undergoing emergency airway
      intervention following cardiovascular collapse were excluded. For each patient,
      we recorded patient demographics, disease severity, anesthesia location, and
      anesthetic technique. RESULTS: One hundred and twenty-nine patients with
      cardiomyopathy underwent a total of 236 anesthetic events, and four cardiac
      arrests were identified. One was related to bradycardia (HR<60), two were
      attributed to bradycardia in association with severe hypotension (systolic blood
      pressure<45), and the fourth arrest was related to isolated severe hypotension.
      Two occurred in the operating suite and two in the CDIU. There was no resulting
      mortality. One patient progressed to heart transplantation. Multiple combinations
      of anesthetic drugs were used for induction of anesthesia. CONCLUSION: We
      performed a review of the last 10 years of anesthesia events in children with
      cardiomyopathy. We report four cardiac arrests in two patients and 236 anesthetic
      events (1.7%). To the best of our knowledge, this is the largest review of these
      patients to date but is limited by its retrospective nature. The low cardiac
      arrest incidence prevents the identification of risk factors and the development
      of a cardiac arrest risk predictive clinical tool.

PMID- 21736664
TI  - Association of betel nut chewing with chronic kidney disease: a retrospective 7
      year study in Taiwan.
AB  - AIM: Only few studies have reported that betel nut (BN) chewing is independently
      associated with chronic kidney disease (CKD); however, the sample size was
      relatively small. This study was to explore further the association between BN
      chewing and CKD using a larger case series. METHODS: We retrospectively reviewed
      the records of a health check-up program from 2003 to 2009. Laboratory tests,
      medical history and status of cigarette smoking, alcohol drinking and BN chewing
      were compared between CKD and non-CKD groups. We checked interaction effects
      between BN chewing and all other covariates, and conducted multivariate logistic
      regression analysis to explore the risk of CKD with BN chewing. RESULTS: A total
      of 27 482 participants (15 491 females and 11 991 males, mean age 58.02 +/- 11.85
      years) were included in the study, of whom 4519 (16.4%) had CKD and 1608 (5.9%)
      chewed BN. CKD prevalence in the chewers was higher than in the non-chewers in
      all age groups per decade. BN chewing was significantly associated with CKD in
      overall subjects (odds ratio (OR) = 1.23, P = 0.027) and also in the male (OR =
      1.23, P = 0.035), non-drinking (OR = 1.62, P = 0.000), non-diabetic (OR = 1.27, P
      = 0.021), and non-proteinuric groups (OR = 1.30, P = 0.013). This relationship
      was insignificant in female, drinking, diabetic and proteinuric groups.
      CONCLUSION: The association between BN chewing and CKD seemed conditional on
      demographics, health behaviours, and underlying co-morbidities. This association
      should be interpreted cautiously.

PMID- 21736665
TI  - A prospective cohort study of healthcare visits and rehospitalizations after
      discharge of patients with community-acquired pneumonia.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to identify the frequency of,
      reasons for, and risk factors associated with additional health-care visits and
      re-hospitalizations (health-care interactions) among patients with community
      acquired pneumonia (CAP), within 30days of discharge from hospital. METHODS: This
      was an observational analysis of a prospective cohort of adults hospitalized with
      CAP at a tertiary hospital in 2007-2009. Additional health-care interactions were
      defined as visits to a primary care centre or emergency department, and hospital
      readmissions within 30days of discharge. RESULTS: Of the 934 patients
      hospitalized with CAP, 282 (34.1%) had additional health-care interactions within
      30days of discharge from hospital; 149 (52.8%) required an additional visit to a
      primary care centre and 177 (62.8%) attended the emergency department. Seventy
      two patients (25.5%) were readmitted to hospital. The main reasons for additional
      health-care interactions were worsening of signs or symptoms of CAP and new or
      worsening comorbidities that were unrelated to pneumonia, mainly cardiovascular
      and pulmonary diseases. The only independent factor associated with visits to a
      primary care centre or the emergency department was alcohol abuse (OR 1.65; 95%
      CI: 1.03-2.64). Hospitalization in the previous 90days (OR 2.47; 95% CI: 1.11
      5.52) and comorbidities (OR 3.99; 95% CI: 1.12-14.23) were independently
      associated with re-hospitalization. CONCLUSIONS: Additional health-care visits
      and re-hospitalizations within 30days of discharge from hospital were common
      among patients with CAP. This was mainly due to worsening of signs or symptoms of
      CAP and/or comorbidities. These findings may have implications for discharge
      planning and follow up of patients with CAP.

PMID- 21736666
TI  - Effect of Ramadan fasting on maternal oxidative stress during the second
      trimester: a preliminary study.
AB  - AIM: To evaluate whether fasting during Ramadan has any significant effects on
      maternal oxidative stress or fetal health in healthy, pregnant women with an
      uncomplicated, second-trimester, singleton pregnancy. METHODS: During the month
      of Ramadan, 1-29 September 2008, 42 fasting and 30 non-fasting pregnant women
      were enrolled in this prospective controlled study. Total antioxidant status
      (TAS), total oxidant status (TOS) and the oxidative stress index (OSI) were
      measured from maternal serum samples taken on a fasting day during Ramadan. The
      two groups underwent routine follow-up examinations. At the end of the pregnancy,
      maternal complications, birth weight and maternal weight gain during the entire
      pregnancy were noted. To evaluate whether the duration of fasting days (>=10 or
      >=15 days) had any significant effects on maternal oxidative stress, pregnant
      women who observed Ramadan for more than nine days or those who fasted for more
      than 14 days were compared with the control group in terms of TAS, TOS and OSI.
      RESULTS: No significant differences were observed between the groups studied in
      terms of TAS, TOS, OSI, maternal age, gestational age, parity, birth weight or
      weight gain during the pregnancy. The TAS level was evaluated as significantly
      higher (P = 0.027) in the >=10 fasting days group compared to the non-fasting
      control group, while there were no significant differences between the groups
      with respect to TOS and OSI. CONCLUSION: Maternal fasting during Ramadan during
      the second trimester does not have a significant effect on maternal oxidative
      stress, fetal development or fetal birth weight.

PMID- 21736667
TI  - Sleep deprivation, physical activity and low income are risk factors for
      inadequate weight gain during pregnancy: a cohort study.
AB  - AIM: To determine the possible risk factors for inadequate gestational weight
      gain. METHODS: A population-based cohort study was carried out in Sri Lanka from
      May 2001 to April 2002. Pregnant women were recruited on or before 16 weeks'
      gestation and followed up until delivery; the sample size was 710. Trimester
      specific exposure status and potential confounding factors were gathered on
      average at the 12th, 28th and 36th weeks of gestation. Maternal weight was
      measured at the first antenatal clinic visit and at delivery. Inadequate weight
      gain was defined as weight gain below the Institute of Medicine recommendations
      in 2009. Multiple logistic regression was applied and the results were expressed
      as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The risk
      factors for inadequate weight gain were low per-capita monthly income (OR 1.63,
      95% CI 1.03, 2.58), multiparity (OR 1.96, 95% CI 1.34, 2.87), sleeping <8 h/day
      during the second, third, or both second and third trimesters (OR 1.60, 95% CI
      1.05, 2.46), standing and walking >=5 h/day during the second trimester (OR 1.50,
      95% CI 1.04, 2.15), and the newborn being of the male sex (OR 1.50, 95% CI 1.04,
      2.16), controlling for the effect of body mass index and gestational age.
      CONCLUSIONS: Risk factors for inadequate gestational weight gain were low income,
      being multiparous, sleep deprivation, physical activity in terms of standing and
      walking, and the male sex of baby.

PMID- 21736668
TI  - Uterine inversion due to a leiomyoma on postpartum day 41: a case report.
AB  - Uterine leiomyomas are common tumors in women of reproductive age and are
      frequently detected during pregnancy. The major complications during pregnancy
      include abortion, preterm delivery, abruptio placentae, intrauterine growth
      retardation, dystocia, and postpartum hemorrhage. Little attention is given to
      uterine leiomyomas postpartum compared to leiomyomas prior to childbirth. In the
      present case, a 27-year-old woman, gravida 1 para 1, presented with massive
      vaginal bleeding, urinary retention and lower abdominal pain on postpartum day
      41. She was diagnosed with uterine inversion due to leiomyoma. After a vaginal
      myomectomy, the uterus was re-placed with a combined vaginal and abdominal
      approach. Because of timely medical intervention, the patient managed to overcome
      the crisis and her reproductive organs were successfully preserved.

PMID- 21736669
TI  - Recombinant activated factor VII as a promising adjuvant therapy for postpartum
      hemorrhage in the practice of obstetric anesthesia: experience from a university
      hospital in Taiwan.
AB  - Massive postpartum hemorrhage is one of the major complications in the peripartum
      period. In some critical cases, hemostasis is hard to achieve even after a
      hysterectomy has been performed. Recombinant activated factor VII has been
      reported as a promising adjuvant therapy for obstetric hemorrhage, although it
      remains unlicensed for this indication. Eight cases receiving recombinant
      activated factor VII in postpartum hemorrhage refractory to the conventional
      therapy in a Taiwanese hospital were analyzed retrospectively. A good response,
      defined as bleeding control in 15 min, was achieved in six patients (75%) with a
      single dose ranging from 55 to 105 ug/kg. The two patients with a poor response
      were later discovered to have had unsolved birth canal injuries. No drug-related
      adverse effects were noted. We recommend that any surgical bleeding should first
      be controlled, as well as the correction of metabolic and hematological
      abnormalities; however, in the situation of intractable postpartum hemorrhage,
      recombinant activated factor VII offers a salvage therapy and should be
      considered early, even before hysterectomy.

PMID- 21736670
TI  - Pheochromocytoma-related cardiomyopathy during the antepartum period in a preterm
      pregnant woman.
AB  - We report a rare case of pheochromocytoma-related cardiomyopathy during the
      preterm period. The patient was a 33-year-old woman who was referred to our
      hospital at 34 weeks' gestation. Her pulse was 130 beats/min, blood pressure of
      186/90 mmHg and oxygen saturation was 30-40%. Fetal bradycardia prompted an
      emergency cesarean section and, nine minutes after admission, a boy weighing 2774
      g was delivered with Apgar scores of 2 at 1 min and 5 at 5 min. A preoperative
      echocardiogram showed reduced fractional shortening of 19%. At 8 h after the
      operation, cardiac arrest developed. An intra-aortic balloon pump and
      percutaneous cardiopulmonary support were inserted, and continuous
      hemodiafiltration was also commenced, after which her cardiac function and
      respiratory function gradually improved. Urinary catecholamine levels were
      elevated and abdominal computerized tomography confirmed the presence of a right
      suprarenal mass. Four months after delivery, she underwent a laparoscopic
      adrenalectomy and the mass was found to be a pheochromocytoma.

PMID- 21736671
TI  - Failure of mid-trimester pregnancy termination: ruptured rudimentary uterine horn
      pregnancy.

PMID- 21736672
TI  - Actinomycotic oophoritis misdiagnosed as an ovarian tumor.

PMID- 21736673
TI  - Functional splicing assay of DSPP mutations in hereditary dentin defects.
AB  - OBJECTIVE: Dentin sialophosphoprotein (DSPP) gene mutations have been identified
      in isolated hereditary dentin defects; however, the genotype-phenotype
      correlations are poorly understood. We performed in vitro splicing assays to test
      the hypothesis that DSPP mutations in splice junctions as well as proposed
      missense/nonsense mutations experimentally result in aberrant pre-mRNA splicing.
      MATERIALS AND METHODS: The genomic fragment of the human DSPP gene was cloned
      into the pSPL3 splicing vector, and previously reported as well as informative de
      novo mutations were then introduced by PCR mutagenesis. The COS-7 cells were
      transfected with each plasmid vector, and total RNA was isolated. RT-PCR result
      was analyzed, and the band intensity of the product was calibrated using ImageJ.
      RESULTS: The predictions by others of exon 3 skipping in specific DSPP mutations
      have been validated and a cryptic splicing donor site has been identified.
      However, the degree of mutational effect on pre-mRNA splicing varied considerably
      depending on the changed nucleotide. CONCLUSIONS: The predictions of exon 3
      skipping in specific DSPP mutations have been validated, and a cryptic splicing
      donor site has been identified. Our data may provide insight into the
      contribution of DSPP mutations in the pathogenesis and genotype-phenotype
      correlations of hereditary dentin defects.

PMID- 21736674
TI  - The harmonics of rodent pulmonary hypertension models.

PMID- 21736675
TI  - The other pulmonary hypertension: heart failure with preserved ejection fraction.

PMID- 21736676
TI  - The management of pregnancy and pregnancy-related medical conditions in pulmonary
      arterial hypertension patients.
AB  - Pulmonary arterial hypertension (PAH) is a complex disorder in which pulmonary
      arterial obstruction leads to elevated pulmonary arterial resistance and right
      ventricular failure. Normal physiologic changes that occur during pregnancy and
      immediately postpartum may produce fatal consequence in PAH patients. Pregnancy
      in patients with PAH has a high maternal mortality, estimated at 30-56%.
      Contemporary estimates of mortality are better but still prohibitively high.
      Current guidelines recommend that pregnancy be avoided or terminated early in
      women with PAH. Some patients, despite counselling by their physician, choose to
      continue with their pregnancy. In addition, some women first present with PAH
      during pregnancy leading to complex management issues in a high-risk patient. PAH
      specific therapies may allow patients to better tolerate pregnancy. These
      patients should be treated by experienced physicians at tertiary care centres.
      This review article will focus on the management of the pregnant PAH patient and
      the preventative options available for this high-risk cohort.

PMID- 21736677
TI  - Rodent models of pulmonary hypertension: harmonisation with the world health
      organisation's categorisation of human PH.
AB  - The WHO classification of pulmonary hypertension (PH) recognises five distinct
      groups, all sharing a mean, resting, pulmonary artery pressure (PAP) > 25 mmHg.
      The aetiology of PH varies by group (1-pulmonary vascular disease, 2-high left
      heart filling pressures, 3-hypoxia, 4-unresolved pulmonary embolism and 5
      miscellaneous). Inclusion in a group reflects shared histological, haemodynamic
      and pathophysiological features and has therapeutic implications. Advantages of
      using rodent models to understand the pathophysiology of human PH and to test
      experimental therapies include the economy, safety and mechanistic certainty they
      provide. As rodent models are meant to reflect human PH, they should be
      categorised by a parallel PH classification and limitations in achieving this
      ideal recognised. Challenges with rodent models include: accurate phenotypic
      characterisation (haemodynamics, histology and imaging), species and strain
      variations in the natural history of PH, and poor fidelity to the relevant human
      PH group. Rat models of group 1 PH include: monocrotaline (+/- pneumonectomy),
      chronic hypoxia + SU-5416 (a VEGF receptor inhibitor) and the fawn-hooded rat
      (FHR). Mouse models of group 1 PH include: transgenic mice overexpressing the
      serotonin transporter or dominant-negative mutants of bone morphogenetic protein
      receptor-2. Group 1 PH is also created by infecting S100A4/Mts1 mice with gamma
      herpesvirus. The histological features of group 1 PH, but not PH itself, are
      induced by exposure to Schistosoma mansoni or Stachybotrys chartarum. Group 3 PH
      is modelled by exposure of rats or mice to chronic hypoxia. Rodent models of
      groups 2, 4 and 5 PH are needed. Comprehensive haemodynamic, histological and
      molecular phenotyping, coupled with categorisation into WHO PH groups, enhances
      the utility of rodent models.

PMID- 21736678
TI  - Transforming growth factor signalling: a common pathway in pulmonary arterial
      hypertension and systemic sclerosis.
AB  - Pulmonary arterial hypertension (PAH) is a clinical condition characterised by
      the presence of precapillary pulmonary hypertension (PH). Included within the
      subcategorisation of PAH are heritable (HPAH) and PAH associated various
      conditions (APAH) including systemic sclerosis (SSc). The pathogenesis of HPAH
      and SSc has been linked to both a genetic predisposition and epigenetic factors.
      TGF-beta superfamily signalling has also been implicated in the development of
      these conditions. In this review, we discuss the role of genetic predisposition,
      epigenetic factors along with dysregulation in TGF-beta superfamily signalling in
      the pathogenesis of PAH and SSc.

PMID- 21736679
TI  - Inflammatory polyps following successful HLA-matched cord blood transplantation
      in a patient with X-linked lymphoproliferative syndrome.
AB  - Gastrointestinal complications following HSCT are numerous and include a variety
      of issues resulting in hepatic, biliary, pancreatic, and intestinal compromise.
      In the context of an underlying state of immune dysregulation, novel
      complications may arise including autoimmunity. To our knowledge, this is the
      first report of a patient with XLP who was successfully treated with HSCT using
      an HLA-matched unrelated cord blood unit that was complicated by the development
      of inflammatory polyps of the colon. Given the underlying diagnosis of XLP and
      its associated immune dysregulation, the challenge of understanding unique
      gastrointestinal manifestations of autoimmunity following HSCT is discussed.

PMID- 21736680
TI  - Norovirus and severe chronic gastroenteritis in pediatric stem cell
      transplantation: the plot thickens.

PMID- 21736681
TI  - Therapeutic drug monitoring is essential for intravenous busulfan therapy in
      pediatric hematopoietic stem cell recipients.
AB  - Busulfan is widely used for myeloablative conditioning in HSCT. Intravenous
      busulfan has been introduced to reduce interindividual variability in plasma
      levels especially in pediatric patients. TDM of intravenous busulfan was
      performed in 34 pediatric HSCT patients with malignant (n = 9) and non-malignant
      (n = 25) diseases (50% of patients <three yr) in a single-center analysis (2006
      2009). Intravenous busulfan was administered twice daily in a four-h infusion
      according to recommended weight-based doses. Busulfan drug levels were measured,
      and pharmacokinetic analysis was performed. The targeted busulfan exposure was
      aimed to range between AUC of 9000-12, 000 ng/mL/h. In 23/34 patients (68%), the
      busulfan dose had to be adjusted at least once. In 16/23 patients (70%), the dose
      had to be increased in a range of 7 to 33%, while in 7/23 patients (30%), the
      dose had to be decreased by 7-20%. The need of dose adjustment was not related to
      weight, age, or underlying disease. Seven out of 34 patients (21%) <20 months
      experienced VOD despite that their total AUCs were within the target AUC. TDM of
      intravenous busulfan is essential to increase the efficacy and safety of busulfan
      based conditioning protocols in pediatric HSCT recipients.

PMID- 21736682
TI  - How ready are they? Parents of pediatric solid organ transplant recipients and
      the transition from hospital to home following transplant.
AB  - Poor discharge transition is evidence of a gap between evidence-based practices
      and current health care delivery. Pediatric SOT recipients are a vulnerable
      population at risk of complications during the discharge transition. The aim of
      this study was to investigate factors associated with the transition care from
      hospital to home. We studied the transition experience of parents of heart,
      liver, or kidney recipients to identify opportunities for improvement in
      discharge and post-discharge care processes and outcomes. Thirty-seven parents
      from three different pediatric transplant centers completed questionnaires on the
      day of hospital discharge and three wk following hospital discharge. Care
      coordination was associated with readiness for hospital discharge. Readiness for
      hospital discharge was subsequently associated with post-discharge coping
      difficulty, adherence difficulty with medical follow-up, and family impact.
      Identifying parents who are not ready to go home provides an opportunity to offer
      additional support services so parents can effectively manage their child's
      recovery and continuing care at home.

PMID- 21736683
TI  - The socioeconomic and psychosocial circumstances of adult long-term survivors of
      hematopoietic stem cell transplantation in childhood.
AB  - Socioeconomic factors such as education, employment, financial circumstances,
      marital status, and psychological well-being were investigated in 51 Swedish
      adults (age 19-42) surviving for at least five yr following pediatric allogeneic
      SCT (age at SCT 1-16 yr) using items derived from a Living Condition Survey
      (ULF). Psychological well-being and cognitive faculties were measured by HAD and
      SWED-QUAL. Socioeconomic data and marital status were compared with a norm group
      matched for gender and age, derived from the Swedish national population
      registry. Most subjects function well and lead normal lives, and they are
      nevertheless more likely than the norm to encounter problems with establishing
      themselves on the labor market. The SCT group demonstrated a lower level of
      employment, and the likelihood of having a disability pension was higher than in
      the normal population. Younger subjects and women encountered most financial
      difficulties and a higher risk of poverty. Cognitive difficulties intercorrelated
      both with inferior financial circumstances and with higher levels of anxiety and
      depression. These results indicate the importance of recognizing and attempting
      to tackle the possible cumulative disadvantage of problems that affect the adult
      following SCT in childhood.

PMID- 21736684
TI  - Recruitment of cellular clathrin to viral factories and disruption of clathrin
      dependent trafficking.
AB  - The viral factories of mammalian reovirus (MRV) are cytoplasmic structures that
      serve as sites of viral genome replication and particle assembly. A 721-aa MRV
      non-structural protein, uNS, forms the factory matrix and recruits other viral
      proteins to these structures. In this report, we show that uNS contains a
      conserved C-proximal sequence (711-LIDFS-715) that is similar to known clathrin
      box motifs and is required for recruitment of clathrin to viral factories.
      Clathrin recruitment by uNS occurs independently of infecting MRV particles or
      other MRV proteins. Ala substitution for a single Leu residue (mutation L711A)
      within the putative clathrin-binding motif of uNS inhibits clathrin recruitment,
      but does not prevent formation or expansion of viral factories. Notably, clathrin
      dependent cellular functions, including both endocytosis and secretion, are
      disrupted in cells infected with MRV expressing wild-type, but not L711A, uNS.
      These results identify uNS as a novel adaptor-like protein that recruits cellular
      clathrin to viral factories, disrupting normal functions of clathrin in cellular
      membrane trafficking. To our knowledge, this is the only viral or bacterial
      protein yet shown to interfere with clathrin functions in this manner. The
      results additionally establish a new approach for studies of clathrin functions,
      based on uNS-mediated sequestration.

PMID- 21736685
TI  - alpha-Adducin translocates to the nucleus upon loss of cell-cell adhesions.
AB  - The F-actin binding protein adducin plays an important role in plasma membrane
      stability, cell motility and cell-cell junctions. In this study, we demonstrate
      that alpha-adducin is mainly localized in the nucleus of sparsely cultured
      epithelial cells, whereas it is localized at cell-cell junctions when the cells
      are grown to confluence. Disruption of cell-cell adhesions induces a nuclear
      translocation of alpha-adducin. Conversely, alpha-adducin is redistributed to the
      cytoplasm and cell-cell junctions in the process of establishing cell-cell
      adhesions. We identify that alpha-adducin contains a bipartite nuclear
      localization signal (NLS) in its COOH-terminal tail domain and a nuclear export
      signal in its neck region. The phosphorylation of alpha-adducin at Ser716 that is
      immediately adjacent to the NLS appears to antagonize the function of the NLS.
      Moreover, we show that depletion of alpha-adducin has adverse effects on cell
      cell adhesions and, to our surprise, cell proliferation. The impaired cell
      proliferation is associated with mitotic defects characterized by disorganized
      mitotic spindles, aberrant chromosomal congregation/segregation and abnormal
      centrosomes. Taken together, our results not only reveal the mechanism for alpha
      adducin to shuttle between the cytoplasm and nucleus, but also highlight a
      potential role for alpha-adducin in mitosis.

PMID- 21736686
TI  - Phosphatidylinositol-3,5-bisphosphate: no longer the poor PIP2.
AB  - Phosphoinositides play an important role in organelle identity by recruiting
      effector proteins to the host membrane organelle, thus decorating that organelle
      with molecular identity. Phosphatidylinositol-3,5-bisphos- phate [PtdIns(3,5)P(2)
      ] is a low-abundance phosphoinositide that predominates in endolysosomes in
      higher eukaryotes and in the yeast vacuole. Compared to other phosphoinositides
      such as PtdIns(4,5)P(2) , our understanding of the regulation and function of
      PtdIns(3,5)P(2)  remained rudimentary until more recently. Here, we review many
      of the recent developments in PtdIns(3,5)P(2)  function and regulation.
      PtdIns(3,5)P(2)  is now known to espouse functions, not only in the regulation of
      endolysosome morphology, trafficking and acidification, but also in autophagy,
      signaling mediation in response to stresses and hormonal cues and control of
      membrane and ion transport. In fact, PtdIns(3,5)P(2)  misregulation is now linked
      with several human neuropathologies including Charcot-Marie-Tooth disease and
      amyotrophic lateral sclerosis. Given the functional versatility of
      PtdIns(3,5)P(2) , it is not surprising that regulation of PtdIns(3,5)P(2) 
      metabolism is proving rather elaborate. PtdIns(3,5)P(2)  synthesis and turnover
      are tightly coupled via a protein complex that includes the Fab1/PIKfyve lipid
      kinase and its antagonistic Fig4/Sac3 lipid phosphatase. Most interestingly, many
      PtdIns(3,5)P(2)  regulators play simultaneous roles in its synthesis and
      turnover.

PMID- 21736687
TI  - Reducing cardiovascular disease risk in patients with type 2 diabetes and
      concomitant macrovascular disease: can insulin be too much of a good thing?
AB  - Despite improvement of microvascular outcomes as a consequence of optimal glucose
      control in patients with type 2 diabetes, prevention of macrovascular
      complications is still a major challenge. Of interest, large-scale intervention
      studies (Action to Control Cardiovascular Risk in Diabetes, Action in Diabetes
      and Vascular Disease-Preterax and Diamicron Modified Release Controlled
      Evaluation and Veterans Affairs Diabetes Trial) comparing standard therapy versus
      more intensive glucose-lowering therapy failed to report beneficial impacts on
      macrovascular outcomes. Consequently, it is currently under debate whether the
      high doses of exogenous insulin that were administered in these trials to achieve
      strict target glucose levels could be responsible for these unexpected outcomes.
      Additionally, a potential role for plasma insulin levels in predicting
      macrovascular outcomes has emerged in patients with or without type 2 diabetes.
      These observations, combined with evidence from in vitro and animal experiments,
      suggest that insulin might have intrinsic atherogenic effects. In this review, we
      summarize clinical trials, population-based studies as well as data emerging from
      basic science experiments that point towards the hypothesis that the
      administration of high insulin doses might not be beneficial in patients with
      type 2 diabetes and established macrovascular disease.

PMID- 21736688
TI  - The safety profile of exogenous insulin in people with type 2 diabetes:
      justification for concern.
AB  - There is no doubt about the value of exogenous insulin for people with type 1
      diabetes. The purpose of this commentary is to discuss emerging evidence that
      this may not be the case for the majority of people with type 2 diabetes.

PMID- 21736689
TI  - Tigerinin-1R: a potent, non-toxic insulin-releasing peptide isolated from the
      skin of the Asian frog, Hoplobatrachus rugulosus.
AB  - AIM: Characterization of peptides in the skin of the Vietnamese common lowland
      frog Hoplobatrachus rugulosus with the ability to stimulate insulin release in
      vitro and improve glucose tolerance in vivo. METHODS: Peptides in an extract of
      skin were purified by reversed-phase HPLC, and their abilities to stimulate the
      release of insulin and the cytosolic enzyme lactate dehydrogenase were determined
      using BRIN-BD11 clonal beta cells. Insulin-releasing potencies of synthetic
      peptides and their effects on membrane potential and intracellular Ca2+
      concentration were also measured using BRIN-BD11 cells. Effects on glucose
      tolerance and insulin release in vivo were determined in mice fed a high-fat diet
      to induce obesity and insulin resistance. RESULTS: A cyclic dodecapeptide
      (RVCSAIPLPICH.NH2), termed tigerinin-1R, was isolated from the skin extract that
      lacked short-term cytotoxic and haemolytic activity but significantly (p < 0.01)
      stimulated the rate of release of insulin from BRIN-BD11 cells at concentrations
      >= 0.1 nM. The maximum response was 405% of the basal rate at 5.6 mM ambient
      glucose concentration and 290% of basal rate at 16.7 mM glucose. C-terminal alpha
      amidation was necessary for high potency and a possible mechanism of action of
      the peptide-involved membrane depolarization and an increase in intracellular
      Ca2+ concentration. Administration of tigerinin-1R (75 nmol/kg body weight) to
      high fat-fed mice significantly (p < 0.05) enhanced insulin release and improved
      glucose tolerance during the 60-min period following an intraperitoneal glucose
      load. CONCLUSION: Tigerinin-1R is a potent, non-toxic insulin-releasing peptide
      that shows potential for development into an agent for the treatment of type 2
      diabetes.

PMID- 21736690
TI  - Causes of renal forniceal rupture.
AB  - What's known on the subject? and What does the study add? Renal forniceal rupture
      is a common finding in patients with ureteral obstruction. It is thought to be
      due to increased renal pelvis pressure from backup of urine, causing one or more
      renal fornices to leak urine. This phenomenon has not been systematically
      studied. Herein we retrospectively review the causes and associated clinical
      findings in over 100 cases of renal forniceal rupture. OBJECTIVE: * To perform a
      retrospective review aiming to identify causes of renal forniceal rupture.
      PATIENTS AND METHODS: * A retrospective review was performed of the longitudinal
      medical record and CT records for patients identified as having renal 'forniceal
      rupture' or 'calyceal rupture' using a radiological database. RESULTS: * In
      total, 108 patients were identified with the CT diagnosis of renal 'forniceal' or
      'calyceal' rupture. * Forniceal rupture was caused by ureteric stones in 80 cases
      (74.1%), malignant extrinsic ureteric compression in nine cases (8.3%), benign
      extrinsic ureteric compression in two cases (1.9%), pelvic-ureteric junction
      obstruction in two cases (1.9%), vesico-ureteric junction (VUJ) obstruction in
      one case (0.9%), bladder outlet obstruction in one case (0.9%) and iatrogenic
      causes in four cases (3.7%). * No definitive cause was found in nine cases
      (8.3%). For patients in whom a ureteric stone was the cause of forniceal rupture,
      the level of obstruction was proximal ureter in 24.3% of cases, distal ureter in
      17.6% of cases and VUJ in 58.1% of cases. * Mean (sd) stone size was 4.09 (2.0)
      mm. Mean (sd) stone size was 5.34 (1.87) mm for proximal stones, 4.08 (1.69) mm
      for distal stones and 3.53 (1.96) mm for VUJ stones (P= 0.005). * Urinary tract
      infection was present in five out of 97 patients (5.2%) in whom data were
      available for analysis. CONCLUSION: * The most common aetiology of renal
      forniceal rupture is obstruction caused by distal ureteric stones followed by
      malignant extrinsic ureteric compression.

PMID- 21736692
TI  - Effect of intra-observer variation in prostate volume measurement on prostate
      specific antigen density calculations among prostate cancer active surveillance
      participants.
AB  - What's known on the subject? and What does the study add? The Epstein criteria,
      which utilize prostate specific antigen density (PSAD) benchmarks, are recognized
      to be a reasonable method of selecting men for active surveillance of prostate
      cancer. Transrectal ultrasonography, however, may not be a sufficiently precise
      method of measuring prostate volume for the determination of PSAD. This study
      shows that despite impressive intra-observer variability in transrectal
      ultrasonography guided prostate volume measurements, this variability typically
      does not affect the PSAD to an extent by which qualification for active
      surveillance would be altered. OBJECTIVE: * To determine intra-observer
      variability in transrectal ultrasonography (TRUS) guided prostate volume
      measurements in the Johns Hopkins active surveillance group and to establish
      whether or not this variability could affect prostate-specific antigen density
      (PSAD) estimates in this cohort. PATIENTS AND METHODS: * In all, 253 patients
      with a combined total of 1111 prostate biopsies underwent TRUS-guided prostate
      volume measurements performed by the same physician at least three times over the
      course of their care. * Coefficients of variation (CV) were calculated for each
      set of measurements performed on each patient by the same physician, and average
      CVs were determined for each physician and for physicians overall. The CVs were
      correlated with the average of each patient's measured prostate volumes to look
      for any trend. * Finally, measured prostate volumes were used with each patient's
      initial prostate-specific antigen (PSA) value to calculate PSAD to reveal whether
      or not the degree of variability found in these measurements would have led to
      PSADs that would have otherwise precluded qualification for active surveillance.
      RESULTS: * The average CV for all sets of prostate volume data was 0.168. Average
      CVs for each physician ranged from 0.136 to 0.234. * However, actual CVs ranged
      anywhere from 0.013 to 0.549. The CVs were found to have no correlation with
      prostate volumes (Pearson correlation coefficient: 0.04). * In 95% of cases,
      variability in TRUS-guided prostate volume measurement did not affect PSAD
      sufficiently to elicit a value greater than 0.15. CONCLUSIONS: * Even among
      individuals who are highly experienced in TRUS-guided prostate volume
      measurement, significant intra-observer variation exists. However, this
      variability is not enough to affect one's eligibility for prostate cancer active
      surveillance when PSAD criteria are used. * The TRUS-guided prostate volume
      measurements remain a reliable method of assessing PSAD in patients with prostate
      cancer.

PMID- 21736693
TI  - Obesity and prostate enlargement in men with localized prostate cancer.
AB  - What's known on the subject? and What does the study add? Obesity is associated
      with prostate enlargement in men without prostate cancer. This study demonstrates
      an association between obesity and prostate enlargement in men with prostate
      cancer, and leads to possible implications for prostate cancer screening and
      diagnosis. OBJECTIVE: * To determine if obesity is associated with prostate size
      in men with prostate cancer. PATIENTS AND METHODS: * We examined preoperative
      body mass index (BMI) and whole prostate weight in a cohort of 16,325 patients
      undergoing radical prostatectomy for localized prostate cancer from 1975 to 2008
      at a single institution. * We used multivariable regression modelling adjusting
      for age, year of surgery, preoperative serum prostate-specific antigen (PSA),
      pathological stage and Gleason grade. RESULTS: * Of the entire cohort, 13,343
      (82%) patients had a prostate weight of at least 40 g. These men were older (P <
      0.001), had a higher preoperative BMI (P < 0.002), higher preoperative PSA (P <
      0.001), and were more likely to have pT2 disease (P < 0.001). * In multivariable
      regression, preoperative BMI was associated with increased prostate weight: for
      each 1 kg/m(2) increase in BMI, prostate weight increased by 0.45 g (95% CI 0.35
      0.55, P-trend < 0.001). * Compared with men with BMI < 25 kg/m(2) , men with a
      BMI >=35 kg/m(2) had a 40% (odds ratio 1.40, 95% CI 1.01-1.95) increased risk of
      prostate weight of at least 40 g and a 70% (odds ratio 1.70, 95% CI 1.32-2.20)
      increased risk of prostate weight of at least 50 g. CONCLUSIONS: * In men with
      localized prostate cancer, obesity is associated with an increased risk of
      prostate enlargement. * These data validate other observations linking obesity
      with prostate enlargement and may have important ramifications for prostate
      cancer diagnosis in obese men.

PMID- 21736694
TI  - Real-time magnetic resonance imaging (MRI): anatomical changes during
      physiological voiding in men.
AB  - OBJECTIVE: To investigate the interactions between the bladder, urethra, pelvic
      floor and the function of the prostate during 'normal' voiding. PATIENTS AND
      METHODS: In all, 16 men with no history of urinary incontinence, urgency or
      obstructive voiding dysfunction were enrolled. We analysed the interaction
      between the bladder, urethra, pelvic floor and changes in the prostate during the
      Valsalva manoeuvre and voiding using real-time magnetic resonance imaging
      (rtMRI). The axis through the external sphincter (AES) to pubo-coccygeal line (PC
      line) and the angle between the axis of the os pubis (AOP) and ventral prostate
      (VP) was measured before and at the end of voiding. Additionally, the angle
      between the AOP and the VP was measured during the Valsalva manoeuvre. Change of
      position, or contraction, of the VP was measured. RESULTS: The mean age of the
      men was 69.8 years and mean prostate volume 33.1 mL. Before voiding, the mean AES
      to PC-line was 10.5 mm. At the end of voiding, the mean AES to PC-line was 20 mm.
      The mean angle between AOP/VP was 31.6 degrees  in the storage phase and
      increased to a mean of 54.5 degrees  during voiding. During the Valsalva
      manoeuvre, the angle between the AOP/VP remained constant. There was a mean
      vertical contraction of the VP of 48.25 mm before voiding and a declining of the
      cranio-caudal distance of the VP with a mean of 33.92 mm during voiding.
      CONCLUSIONS: All the men in our study showed relaxation of the pelvic floor,
      followed by a descent of the bladder neck. Voiding could not be initiated unless
      the prostate rotated around the symphysis. The study suggests that both the
      rotation and a vertical contraction of the prostate precede voiding. The anatomy
      of physiological voiding or voiding dysfunction can be investigated non
      invasively using rtMRI.

PMID- 21736695
TI  - Phosphodiesterase type 9 (PDE9) in the human lower urinary tract: an
      immunohistochemical study.
AB  - OBJECTIVES: To examine the roles of the one of the cyclic guanosine monophosphate
      (cGMP)-specific phosphodiesterases (PDEs), PDE9, in human lower urinary tract
      (LUT), we performed immunohistochemistry (IHC) using autopsy specimens. To
      demonstrate the potential functional differences between PDE5 and PDE9 in human
      LUT, the localization of PDE5 and PDE9 was also compared using laser-capture
      microdissection (LCM)/reverse transcriptase-polymerase chain reaction (RT-PCR)
      method. MATERIALS AND METHODS: *  We immunolocalized PDE9 in human bladder (60
      cases) and prostate (40) specimens using IHC. We performed LCM/RT-PCR evaluation
      in six human bladders to determine the differential expression patterns of PDE5
      and PDE9. RESULTS: PDE9 immunoreactivity was detected in the bladder urothelium
      of all the cases and in 85% of the prostatic urethral urothelium. PDE9
      immunoreactivity was detected in the perikaryon of the intramural ganglia. LCM/RT
      PCR evaluation showed that PDE5 mRNA was exclusively detected in smooth muscle
      cells but PDE9 mRNA was mainly detected in the urothelium of the human bladder.
      CONCLUSION: PDE9 is widely distributed in the urothelial epithelium of the human
      LUT and its potential roles may be different from those of PDE5.

PMID- 21736696
TI  - Atrial fibrillation and upper limb thromboembolectomy: a national cohort study.
AB  - BACKGROUND: The risk factors associated with, and the incidence of systemic
      embolism in patients with atrial fibrillation (AF) are poorly understood.
      OBJECTIVES: We studied the association between AF and upper limb
      thromboembolectomy involving brachial, ulnar or radial artery in a national
      cohort study that included all individuals aged 40-99 years with incident AF.
      METHODS: Data were retrieved from the Danish National Vascular Registry, the
      National Registry of Patients, the Danish Civil Registration System and
      Statistics Denmark. RESULTS: In total, 131,476 patients (68,042 men and 63,434
      women) with AF without previous thromboembolectomy in the upper limb were
      registered. In the study cohort, 130 men underwent upper limb thromboembolectomy
      over 220,890 person-years of observation, whilst 275 women underwent
      thromboembolectomy over 197,777 patient-years. The incidence per 100,000 person
      years was 58.9 (95% CI, 49.2-69.8) for men and 139.1 (95% CI, 123.1-156.5) for
      women. The relative risk of thromboembolectomy among patients with AF compared to
      the background population was 7.5 (95% CI, 6.3-8.9) for men, and 9.3 (95% CI, 8.3
      10.5) for women. Women with AF had a relative thromboembolectomy risk of 1.8 (95%
      CI, 1.5-2.3) compared to men with AF. Among patients with AF, history of
      hypertension (HR 2.2-2.9), myocardial infarction (HR 2.9-3.9), heart failure (HR
      1.6-1.9) and stroke (HR 2.2-3.8) were significantly associated with increased
      risk of thromboembolectomy in both men and women. CONCLUSIONS: AF substantially
      increases the risk of upper limb thromboembolectomy. This risk is higher with
      increasing age, female gender, and associated with hypertension, myocardial
      infarction, heart failure and stroke.

PMID- 21736697
TI  - Medication management in the elderly population: in search of the right balance.

PMID- 21736698
TI  - The term "psychogenic pain" should be abolished or changed to "braingenic pain"
      (pain whose affected area is in the brain).

PMID- 21736699
TI  - Low-molecular-weight-heparin and pregnancy, when the dose does it: a
      nephrologist's opinion: a rebuttal.

PMID- 21736701
TI  - Protein alpha-N-acetylation studied by N-terminomics.
AB  - Cotranslational protein N-terminal modifications, including proteolytic
      maturation such as initiator methionine excision by methionine aminopeptidases
      and N-terminal blocking, occur universally. Protein alpha-N-acetylation, or the
      transfer of the acetyl moiety of acetyl-coenzyme A to nascent protein N-termini,
      catalysed by multisubunit N-terminal acetyltransferase complexes, generally takes
      place during protein translation. Nearly all protein modifications are known to
      influence different protein aspects such as folding, stability, activity and
      localization, and several studies have indicated similar functions for protein
      alpha-N-acetylation. However, until recently, protein alpha-N-acetylation
      remained poorly explored, mainly due to the absence of targeted proteomics
      technologies. The recent emergence of N-terminomics technologies that allow
      isolation of protein N-terminal peptides, together with proteogenomics efforts
      combining experimental and informational content have greatly boosted the field
      of alpha-N-acetylation. In this review, we report on such emerging technologies
      as well as on breakthroughs in our understanding of protein N-terminal biology.

PMID- 21736700
TI  - Mother's perceptions and experiences of infant feeding within a community-based
      peer counselling intervention in South Africa.
AB  - Exclusive breastfeeding (EBF) has the potential to significantly reduce infant
      mortality, but is frequently not practiced in low-income settings where infants
      are vulnerable to malnutrition and infections including human immunodeficiency
      virus (HIV). This study explores mothers' experiences of infant feeding after
      receiving peer counselling promoting exclusive breast or formula feeding. This
      qualitative study was embedded in a cluster randomized peer counselling
      intervention trial in South Africa that aimed to evaluate the effect of peer
      counselling on EBF. Participants were selected from the three districts that were
      part of the trial reflecting different socio-economic conditions, rural-urban
      locations and HIV prevalence rates. Seventeen HIV-positive and -negative mothers
      allocated to intervention clusters were recruited. Despite perceived health and
      economic benefits of breastfeeding, several barriers to EBF remained, which
      contributed to a preference for mixed feeding. The understanding of the
      promotional message of 'exclusive' feeding was limited to 'not mixing two milks':
      breast or formula and did not address early introduction of foods and other
      liquids. Further, a crying infant or an infant who did not sleep at night were
      given as strong reasons for introducing semi-solid foods as early as 1 month. In
      addition, the need to adhere to the cultural practice of 'cleansing' and the
      knowledge that this practice is not compatible with EBF appeared to promote the
      decision to formula feed in HIV-positive mothers. Efforts to reduce barriers to
      EBF need to be intensified and further take into account the strong cultural
      beliefs that promote mixed feeding.

PMID- 21736702
TI  - Cytochrome c biogenesis in mitochondria--Systems III and V.
AB  - In c-type cytochromes, heme becomes covalently attached to the polypeptide chain
      by a reaction between the vinyl groups of the heme and cysteine thiols from the
      protein. There are two such cytochromes in mitochondria: cytochrome c and
      cytochrome c(1). The heme attachment is a post-translational modification that is
      catalysed by different biogenesis proteins in different organisms. Three types of
      biogenesis system are found or predicted in mitochondria: System I (the
      cytochrome c maturation system); System III (termed holocytochrome c synthase
      (HCCS) or heme lyase); and System V. This review focuses primarily on cytochrome
      c maturation in mitochondria containing HCCS (System III). It describes what is
      known about the enzymology and substrate specificity of HCCS; the role of HCCS in
      human disease; import of HCCS into mitochondria; import of apocytochromes c and
      c(1) into mitochondria and the close relationships with HCCS-dependent heme
      attachment; and the role of the fungal cytochrome c biogenesis accessory protein
      Cyc2. System V is also discussed; this is the postulated mitochondrial cytochrome
      c biogenesis system of trypanosomes and related organisms. No cytochrome c
      biogenesis proteins have been identified in the genomes of these organisms whose
      c-type cytochromes also have a unique mode of heme attachment.

PMID- 21736703
TI  - Synthesis and biological activity of novel 1-substituted phenyl-4-[N-[(2'
      morpholinothoxy)phenyl]aminomethyl]-1H-1,2,3-triazoles.
AB  - In an attempt to search for potent antifungal agents, a series of novel 1
      substituted phenyl-4-[N-[(2'-morpholinothoxy)phenyl]aminomethyl]-1H-1,2,3
      triazoles 5a-m was designed and synthesized via Huisgen cycloaddition reaction
      between various (2-morpholinoethoxy)-N-(prop-2-ynyl)aniline and different
      azidobenzene. Their chemical structures were characterized by (1) H NMR and
      elemental analysis. A cleaner reaction with milder conditions and satisfactory
      yields was observed in the micorwave-assisted synthesis of 4a-c. The fungicidal
      activity of some target compounds were evaluated in vitro against Fusarium
      omysporum, Physalospora piricola, Alternaria solani, Cercospora arachidicola and
      Gibberella zeae at 50 MUg/mL. The bioassay results indicated that some compounds
      exhibited moderate fungicidal activities. Furthermore, compound 5h displayed
      equal activity to the positive control compounds against Alternaria solani.

PMID- 21736704
TI  - In silico exploration of anti-inflammatory activity of natural coumarinolignoids.
AB  - Natural coumarinolignoids isolated from the seeds of Cleome viscosa consist of a
      racemic mixture of cleomiscosins A, B and C. To screen out potential lead, anti
      inflammatory activity of the isolated compounds was evaluated through molecular
      docking and QSAR studies by using reported in vivo activity of Swiss albino mice.
      Based on docking binding affinity, a possible mechanism of action has been
      hypothesized which constitute toll-like receptors (TLR-4), cluster of
      differentiation molecules (CDs), iNOS, COX-2 and STAT-6 proteins. It was very
      interesting to find that the 3D topology of the active site of COX-2 from the
      docking was in good agreement with QSAR model and in silico ADME/T parameters. A
      forward feed multiple linear regression model was developed with r(2) = 0.92 and
      rCV(2) = 0.87. This study showed that chemical descriptors, for example dipole
      vector-X, dipole vector-Y, steric energy, LUMO energy, size of smallest ring,
      size of largest ring and carboxyl group count, correlate reasonably well with
      experimental in vivo activity (logLD(50) ). QSAR study indicates that dipole
      vector-Y and carboxyl group count have negative correlation with activity.
      Cleomiscosins also showed compliance with 95% of in silico ADME/T properties of
      available drugs, e.g. serum protein binding, blood-brain barrier, CNS activity,
      HERG K+ channel activity, apparent Caco-2 permeability, apparent MDCK
      permeability, skin permeability and human oral absorption in GI. Besides,
      toxicity screening study suggests that cleomiscosin molecules possess no toxicity
      risk parameters. This study offer useful references for understanding and
      molecular design of inhibitors with improved anti-inflammatory activity.

PMID- 21736705
TI  - Induction of labour versus expectant monitoring for gestational hypertension or
      mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a
      multicentre, open-label randomised controlled trial.
AB  - BACKGROUND: Gestational hypertension (GH) and pre-eclampsia (PE) can result in
      severe complications such as eclampsia, placental abruption, syndrome of
      Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even
      neonatal or maternal death. We recently showed that in women with GH or mild PE
      at term induction of labour reduces both high risk situations for mothers as well
      as the caesarean section rate. In view of this knowledge, one can raise the
      question whether women with severe hypertension, pre-eclampsia or deterioration
      chronic hypertension between 34 and 37 weeks of gestation should be delivered or
      monitored expectantly. Induction of labour might prevent maternal complications.
      However, induction of labour in late pre-term pregnancy might increase neonatal
      morbidity and mortality compared with delivery at term. METHODS/DESIGN: Pregnant
      women with severe gestational hypertension, mild pre-eclampsia or deteriorating
      chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be
      asked to participate in a multi-centre randomised controlled trial. Women will be
      randomised to either induction of labour or expectant monitoring. In the
      expectant monitoring arm, women will be induced only when the maternal or fetal
      condition detoriates or at 37+0 weeks of gestation. The primary outcome measure
      is a composite endpoint of maternal mortality, severe maternal complications
      (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and
      progression to severe pre-eclampsia. Secondary outcomes measures are respiratory
      distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and
      vaginal instrumental delivery rates, maternal quality of life and costs. Analysis
      will be intention to treat. The power calculation is based on an expectant
      reduction of the maternal composite endpoint from 5% to 1% for an expected
      increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies
      that 680 women have to be randomised. DISCUSSION: This trial will provide insight
      as to whether in women with hypertensive disorders late pre-term, induction of
      labour is an effective treatment to prevent severe maternal complications without
      compromising the neonatal morbidity. TRIAL REGISTRATION: NTR1792 CLINICAL TRIAL
      REGISTRATION: http://www.trialregister.nl.

PMID- 21736706
TI  - Can apricot kernels fatty acids delay the atrophied hepatocytes from progression
      to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?
AB  - BACKGROUND AND AIMS: The present study was aimed to analyze the chemical
      composition of ground apricot kernel (GAK) and examine its effect on hepatic
      fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats. METHODS AND
      RESULTS: Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg
      DMN for 3 consecutive days each week over a period of 4 wk. The rats were
      randomly assigned to five groups of nine rats each: the negative control group
      (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK
      (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and
      hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed,
      blood was collected and livers were excised for biochemical measurements and
      histological examination. Results indicate that the diet supplemented with GAK
      led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH.
      These results were confirmed by liver histology. Hierarchically high levels f GAK
      (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels.
      CONCLUSION: This study demonstrates that GAK administration specifically (1.5
      mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be
      used as a therapeutic option and preventive measure against hepatic fibrosis.
      Furthermore, a human trial would be applied specially GAK is a part of Egyptian
      diet. The act of why high amounts of GAK was improved biochemical values compared
      to low or moderate levels tested in this study may be due to increase levels of
      oleic acid and other polyphenols in apricot kernels.

PMID- 21736707
TI  - Adult colocolic intussusception diagnosed by ultrasonography: a case report.
AB  - INTRODUCTION: Intussusception is highly uncommon in adults and accounts for only
      5% of all reported cases. It is more commonly secondary to an identifiable bowel
      lesion in 90% of cases, whereas 10% have no discernable cause. Diagnosis is
      difficult due to non-specific symptoms of the disease. Diagnostic imaging plays
      an important role in the diagnosis of the condition. Sonography and computed
      tomography are the most commonly used imaging techniques. In adults,
      intussusception usually requires treatment by surgical resection of the affected
      bowel. CASE PRESENTATION: A 35-year-old Moroccan woman presented with a five
      month history of intermittent abdominal pain and one episode of bleeding from the
      rectum. At physical examination an abdominal mass was noted. Abdominal sonography
      revealed a 6.3 * 8.5 cm midline mass in her upper abdomen that was tender. In
      transverse section, the mass had the multiple concentric rings of hypoechoic and
      echogenic layers associated with the sonographic appearance of intussusception.
      In longitudinal section, the mass had the sonographic aspect of multiple parallel
      lines, giving the so-called "sandwich appearance".A corresponding contrast
      enhanced abdominal computed tomography scan also demonstrated the
      intussusception. Surgery confirmed a colocolic intussusception with a large,
      firm, indurated mass as the lead point. A right hemicolectomy was undertaken
      because of concern about possible malignancy. The resected ascending colon was
      then opened up, to find a protruding tumor of the ascending colon that was acting
      as the lead point. It measured 7.6 * 6.9 * 2.4 cm. Pathology diagnosed an
      infiltrating, differentiated adenocarcinoma of the ascending colon invading
      through the muscularis propria. No lymphovascular invasion was seen. Our patient
      has recovered well. CONCLUSION: Intussusception is relatively rare in the adult
      population, and this, along with the vague clinical features, makes diagnosis
      difficult. Ultrasonography and computed tomography have been proven to be
      effective diagnostic modalities. Ultrasonography can be performed quickly and
      accurately, and is widely available. In adults, intussusception is usually
      associated with an underlying cause and requires treatment by surgical resection.

PMID- 21736708
TI  - Pulmonary intravascular lymphoma diagnosed by 18-fluorodeoxyglucose positron
      emission tomography-guided transbronchial lung biopsy in a man with long-term
      survival: a case report.
AB  - INTRODUCTION: 18-Fluorodeoxyglucose positron emission tomography can detect the
      pulmonary involvement of intravascular lymphoma that presents no abnormality in a
      computed tomography scan. CASE PRESENTATION: We report the case of a 61-year-old
      Japanese man who had pulmonary intravascular lymphoma and no computed tomography
      abnormality. We were able to make an antemortem diagnosis of pulmonary
      intravascular lymphoma by transbronchial lung biopsy according to 18
      fluorodeoxyglucose positron emission tomography findings. He is free of recurrent
      disease 24 months after chemotherapy. CONCLUSIONS: To the best of our knowledge,
      this is the first reported case of a long-term survivor of pulmonary
      intravascular lymphoma diagnosed by transbronchial lung biopsy under the guide of
      18-fluorodeoxyglucose positron emission tomography.

PMID- 21736709
TI  - A 5'-region polymorphism modulates promoter activity of the tumor suppressor gene
      MFSD2A.
AB  - BACKGROUND: The MFSD2A gene maps within a linkage disequilibrium block containing
      the MYCL1-EcoRI polymorphism associated with prognosis and survival in lung
      cancer patients. Survival discrepancies between Asians and Caucasians point to
      ethnic differences in allelic frequencies of the functional genetic variations.
      RESULTS: Analysis of three single-nucleotide polymorphisms (SNPs) mapping in the
      MFSD2A 5'-regulatory region using a luciferase reporter system showed that SNP
      rs12072037, in linkage disequilibrium with the MYCL1-EcoRI polymorphism and
      polymorphic in Asians but not in Caucasians, modulated transcriptional activity
      of the MFSD2A promoter in cell lines expressing AHR and ARNT transcription
      factors, which potentially bind to the SNP site. CONCLUSION: SNP rs12072037
      modulates MFSD2A promoter activity and thus might affect MFSD2A levels in normal
      lung and in lung tumors, representing a candidate ethnically specific genetic
      factor underlying the association between the MYCL1 locus and lung cancer
      patients' survival.

PMID- 21736710
TI  - Regeneration of human bones in hip osteonecrosis and human cartilage in knee
      osteoarthritis with autologous adipose-tissue-derived stem cells: a case series.
AB  - INTRODUCTION: This is a series of clinical case reports demonstrating that a
      combination of percutaneously injected autologous adipose-tissue-derived stem
      cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to
      regenerate bones in human osteonecrosis, and with addition of a very low dose of
      dexamethasone, cartilage in human knee osteoarthritis. CASE REPORTS: Stem cells
      were obtained from adipose tissue of abdominal origin by digesting lipoaspirate
      tissue with collagenase. These stem cells, along with hyaluronic acid, platelet
      rich plasma and calcium chloride, were injected into the right hip of a 29-year
      old Korean woman and a 47-year-old Korean man. They both had a history of right
      hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old
      Korean woman and a 79-year-old Korean woman, both with a long history of knee
      pain due to osteoarthritis, were injected with stem cells along with hyaluronic
      acid, platelet rich plasma, calcium chloride and a nanogram dose of
      dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and
      pain score data were then analyzed. CONCLUSIONS: The MRI data for all the
      patients in this series showed significant positive changes. Probable bone
      formation was clear in the patients with osteonecrosis, and cartilage
      regeneration in the patients with osteoarthritis. Along with MRI evidence, the
      measured physical therapy outcomes, subjective pain, and functional status all
      improved. Autologous mesenchymal stem cell injection, in conjunction with
      hyaluronic acid, platelet rich plasma and calcium chloride, is a promising
      minimally invasive therapy for osteonecrosis of femoral head and, with low-dose
      dexamethasone, for osteoarthritis of human knees.

PMID- 21736711
TI  - Non prescribed sale of antibiotics in Riyadh, Saudi Arabia: a cross sectional
      study.
AB  - BACKGROUND: Antibiotics sales without medical prescriptions are increasingly
      recognized as sources of antimicrobial misuse that can exacerbate the global
      burden of antibiotic resistance. We aimed to determine the percentage of
      pharmacies who sell antibiotics without medical prescriptions, examining the
      potential associated risks of such practice in Riyadh, Saudi Arabia, by
      simulation of different clinical scenarios. METHODS: A cross sectional study of a
      quasi-random sample of pharmacies stratified by the five regions of Riyadh. Each
      pharmacy was visited once by two investigators who simulated having a relative
      with a specific clinical illness (sore throat, acute bronchitis, otitis media,
      acute sinusitis, diarrhea, and urinary tract infection (UTI) in childbearing aged
      women). RESULTS: A total of 327 pharmacies were visited. Antibiotics were
      dispensed without a medical prescription in 244 (77.6%) of 327, of which 231
      (95%) were dispensed without a patient request. Simulated cases of sore throat
      and diarrhea resulted in an antibiotic being dispensed in (90%) of encounters,
      followed by UTI (75%), acute bronchitis (73%), otitis media (51%) and acute
      sinusitis (40%). Metronidazole (89%) and ciprofloxacin (86%) were commonly given
      for diarrhea and UTI, respectively, whereas amoxicillin/clavulanate was dispensed
      (51%) for the other simulated cases. None of the pharmacists asked about
      antibiotic allergy history or provided information about drug interactions. Only
      23% asked about pregnancy status when dispensing antibiotics for UTI-simulated
      cases. CONCLUSIONS: We observed that an antibiotic could be obtained in Riyadh
      without a medical prescription or an evidence-based indication with associated
      potential clinical risks. Strict enforcement and adherence to existing
      regulations are warranted.

PMID- 21736712
TI  - 'Boiled egg' in the peritoneal cavity-a giant peritoneal loose body in a 64-year
      old man: a case report.
AB  - INTRODUCTION: Peritoneal loose bodies, or peritoneal mice, are rare asymptomatic
      lesions that are usually found as an incidental finding during abdominal surgery
      or autopsy. Giant loose bodies, measuring more than 5 cm, are rare and only a few
      cases are reported in the literature. These bodies are usually infarcted
      appendices epiploicae, which become detached and appear as a peritoneal loose
      body in the abdominal cavity. They may re-attach themselves to a surface, such as
      the lower aspect of the spleen or omentum, in which case they can be called a
      "parasitized peritoneal body", as in our case. CASE PRESENTATION: We report a
      case of a giant loose peritoneal body measuring 7 * 5 cm found incidentally in a
      64-year-old Indian man who presented with acute intestinal obstruction. We
      present the current hypothesis and our opinion on the genesis of such large
      bodies and discuss the problems in diagnosis. CONCLUSION: Peritoneal loose bodies
      are common but giant peritoneal loose bodies are very rare. These giant bodies
      usually do not require any treatment until they become complicated. Present
      diagnosis modalities have limitations in the diagnosis of mobile lesions in the
      abdominal cavity, so care must be taken to avoid unnecessary laparotomies in
      uncomplicated cases.

PMID- 21736713
TI  - Internet use, needs and expectations of web-based information and communication
      in childbearing women with type 1 diabetes.
AB  - BACKGROUND: In the childbearing period women use the internet both to seek
      information and as an important source of communication. For women with type 1
      diabetes, pregnancy and early motherhood constitute a more complex situation than
      for women in general. This implies need for support from various professionals
      and a way of bridging any discontinuity in care would be to develop a website
      providing complementary social support and information. The objective of this
      study was to explore internet use, needs, and expectations regarding web-based
      information and communication in childbearing women with type 1 diabetes.
      METHODS: Data were collected via a web-based survey with an explorative and
      descriptive design, in which 105 of 139 eligible mothers with type 1 diabetes and
      recent childbearing experience participated. The data were analyzed with
      descriptive and analytical statistics, and open answers with a directed content
      analysis. RESULTS: Of the 105 women, 22% never used the internet to search for
      information concerning pregnancy, childbirth, and parenthood. 12% searched for
      information every day, 29% one or more times a week, and 38% one or more times a
      month. Of the women 44% declared themselves to be passive participants on social
      websites, and 45% to be active participants. 45% had specific expectations of web
      based support directed towards childbearing, especially those with higher
      educational level (P = .01). Expectations of instrumental and informational
      support included an expert-controlled website with reliable, updated, and
      information focused on childbearing and diabetes, improved access to diabetes
      care professionals and alternative ways to communicate and to receive
      childbearing-related support. The women also asked for online technical devices
      to manage the frequent monitoring of blood glucose during pregnancy. Informal,
      emotional, and appraisal support from women in similar situations was suggested
      as a way to provide an arena for belonging instead of creating feelings of
      alienation. CONCLUSIONS: Our results add important knowledge about the web-based
      needs of women with type 1 diabetes in relation to childbearing. This user
      directed study indicates specific areas of development for the provision of
      effective web-based support that includes facilities for reliable information,
      interactive support and social networking in this population.

PMID- 21736714
TI  - The effects of Bleomycin A5 on infantile maxillofacial haemangioma.
AB  - OBJECTIVE: To examine the effects of bleomycin A5 on infantile maxillofacial
      haemangiomas. METHODS: Bleomycin A5 was given by multiple intralesinoal
      injections and the dosage was given according to the age of the patient and size
      of the lesion. Parts of patients were accompanied by prednisone treatment (2-5
      mg/kg, po, QOD. RESULTS: All the haemangiomas involutes completely after treated
      with bloemycin A5 with better recovery of skin color and less scar forming in
      small haemangiomas. CONCLUSION: Infantile haemangioma could be effectively
      treated with bleomycin A5 without serious side effects.

PMID- 21736715
TI  - Quantitative measurements of inequality in geographic accessibility to pediatric
      care in Oita Prefecture, Japan: standardization with complete spatial randomness.
AB  - BACKGROUND: A quantitative measurement of inequality in geographic accessibility
      to pediatric care as well as that of mean distance or travel time is very
      important for priority setting to ensure fair access to pediatric facilities.
      However, conventional techniques for measuring inequality is inappropriate in
      geographic settings. Since inequality measures of access distance or travel time
      is strongly influenced by the background geographic distribution patterns, they
      cannot be directly used for regional comparisons of geographic accessibility. The
      objective of this study is to resolve this issue by using a standardization
      approach. METHODS: Travel times to the nearest pediatric care were calculated for
      all children in Oita Prefecture, Japan. Relative mean differences were considered
      as the inequality measure for secondary medical service areas, and were
      standardized with an expected value estimated from a Monte Carlo simulation based
      on complete spatial randomness. RESULTS: The observed mean travel times in the
      area considered averaged 4.50 minutes, ranging from 1.83 to 7.02 minutes. The
      mean of the observed inequality measure was 1.1, ranging from 0.9 to 1.3. The
      expected values of the inequality measure varied according to the background
      geographic distribution pattern of children, which ranged from 0.3 to 0.7. After
      standardizing the observed inequality measure with the expected one, we found
      that the ranks of the inequality measure were reversed for the observed areas.
      CONCLUSIONS: Using the indicator proposed in this paper, it is possible to
      compare the inequality in geographic accessibility among regions. Such a
      comparison may facilitate priority setting in health policy and planning.

PMID- 21736716
TI  - Evaluation of long-term antinociceptive properties of stabilized hyaluronic acid
      preparation (NASHA) in an animal model of repetitive joint pain.
AB  - INTRODUCTION: Clinical trials provided controversial results on whether the
      injection of hyaluronan preparations into osteoarthritic joints reduces pain.
      Problems of clinical studies may be the substantial placebo effects of intra
      articular injections, different severity and rate of progression of the disease
      and others. We hypothesize that the use of preclinical pain models may help to
      clarify whether a certain hyaluronan exerts antinociceptive effects upon intra
      articular injection. In the present study we tested in the
      bradykinin/prostaglandin E(2) (PGE(2)) model primarily the putative
      antinociceptive effect of stabilized hyaluronic acid from a non animal source
      (NASHA), a stabilized hyaluronic acid based gel for intra-articular treatment of
      OA. We established a dose-response relationship for NASHA and we compared NASHA
      to other hyaluronans with different formulations that are in clinical use.
      METHODS: To induce transient joint pain episodes bradykinin and PGE(2) were
      repetitively administered intra-articularly and unilaterally into rat knee joints
      during short anaesthesia. After establishment of the predrug nociceptive
      responses, a single intra-articular injection of saline or NASHA at different
      concentrations was administered and pain responses to further bradykinin/PGE(2)
      injections were monitored up to 56 days after NASHA. Furthermore, the obtained
      effective dose was compared to clinically defined concentrations of Hylan GF20
      and sodium hyaluronate. The primary outcome measures were primary mechanical
      hyperalgesia at the knee joint and pain-induced weight bearing. RESULTS: On day 1
      after injection, all tested hyaluronan preparations showed an antinociceptive
      effect >50% compared to saline. Single injections of higher doses of NASHA (50,
      75 and 100 MUl) were antinociceptive up to 56 days. When injection volumes in rat
      knee joints were adapted to clinical injection volumes in humans, the
      antinociceptive effects of the cross-linked NASHA and Hylan GF20 had a longer
      duration than that of the non cross-linked sodium hyaluronate (with a slightly
      better effect of NASHA than Hylan GF20). CONCLUSIONS: In the bradykinin/PGE(2)
      model of joint pain a single injection of all hyaluronan preparations provided
      significant antinociceptive effects compared to saline. It appeared that the
      duration of the antinociceptive effect of the cross-linked hyaluronan
      preparations NASHA and Hylan GF20 was more prolonged. In addition, the gel beads
      structure allowing only a slow release of hyaluronic acid (NASHA) may even
      enhance this prolonged antinociceptive effect.

PMID- 21736717
TI  - Comparing ambient, air-convection, and fluid-convection heating techniques in
      treating hypothermic burn patients, a clinical RCT.
AB  - BACKGROUND: Hypothermia in burns is common and increases morbidity and mortality.
      Several methods are available to reach and maintain normal core body temperature,
      but have not yet been evaluated in critical care for burned patients. Our unit's
      ordinary technique for controlling body temperature (Bair Hugger(r)+ radiator
      ceiling + bed warmer + Hotline(r)) has many drawbacks e.g.; slow and the working
      environment is hampered.The aim of this study was to compare our ordinary heating
      technique with newly-developed methods: the AllonTM2001 Thermowrap (a temperature
      regulating water-mattress), and Warmcloud (a temperature regulating air
      mattress). METHODS: Ten consecutive burned patients (> 20% total burned surface
      area and a core temperature < 36.0 degrees C) were included in this prospective,
      randomised, comparative study. Patients were randomly exposed to 3 heating
      methods. Each treatment/measuring-cycle lasted for 6 hours. Each heating method
      was assessed for 2 hours according to a randomised timetable. Core temperature
      was measured using an indwelling (bladder) thermistor. Paired t-tests were used
      to assess the significance of differences between the treatments within the
      patients. ANOVA was used to assess the differences in temperature from the first
      to the last measurement among all treatments. Three-way ANOVA with the Tukey HSD
      post hoc test and a repeated measures ANOVA was used in the same manner, but
      included information about patients and treatment/measuring-cycles to control for
      potential confounding. Data are presented as mean (SD) and (range). Probabilities
      of less than 0.05 were accepted as significant. RESULTS: The mean increase, 1.4
      (SD 0.6 degrees C; range 0.6-2.6 degrees C) in core
      temperature/treatment/measuring-cycle highly significantly favoured the
      AllonTM2001 Thermowrap in contrast to the conventional method 0.2 (0.6) degrees C
      (range -1.2 to 1.5 degrees C) and the Warmcloud 0.3 (0.4) degrees C (range -0.4
      to 0.9 degrees C). The procedures for using the AllonTM2001 Thermowrap were
      experienced to be more comfortable and straightforward than the conventional
      method or the Warmcloud. CONCLUSIONS: The AllonTM2001 Thermowrap was more
      effective than the Warmcloud or the conventional method in controlling patients'
      temperatures.

PMID- 21736718
TI  - Myocardial bridging causing ischemia and recurrent chest pain: a case report.
AB  - BACKGROUND: Myocardial bridging is present when a segment of a major epicardial
      coronary artery runs intramurally through the myocardium. It usually has a benign
      prognosis, but in some cases myocardial ischemia, infarction and sudden cardiac
      death have been reported. We are here reporting a case of myocardial bridging
      which was complicated with recurrent chest pain and transient ST-segment
      elevation during exercise treadmill test. CASE PRESENTATION: A 40 year-old-man
      presented with recurrent retrosternal chest pain of 2 months duration. He had
      history of smoking and was obese, otherwise no physical abnormalities were
      detected by examination. Electrocardiogram and blood tests were normal apart from
      impaired glucose tolerance with elevated triglycerides and decreased level of
      high density lipoprotein cholesterol. While doing exercise treadmill test, the
      patient developed chest pain and significant ST-segment elevation in almost all
      precordial leads that persisted for about 15 minutes through recovery. We decided
      to admit the patient to the coronary care unit for further management and to
      perform coronary angiogram. Myocardial bridging was observed in the mid segment
      of the left anterior descending coronary artery. Medical treatment was decided.At
      one year follow up, our patient was healthy and had no cardiac complaints. In
      conclusion, myocardial bridging may predispose to coronary vasospasm that may
      leads to ischemic complications.

PMID- 21736719
TI  - Genetic diversity of Streptococcus suis isolates as determined by comparative
      genome hybridization.
AB  - BACKGROUND: Streptococcus suis is a zoonotic pathogen that causes infections in
      young piglets. S. suis is a heterogeneous species. Thirty-three different
      capsular serotypes have been described, that differ in virulence between as well
      as within serotypes. RESULTS: In this study, the correlation between gene
      content, serotype, phenotype and virulence among 55 S. suis strains was studied
      using Comparative Genome Hybridization (CGH). Clustering of CGH data divided S.
      suis isolates into two clusters, A and B. Cluster A isolates could be
      discriminated from cluster B isolates based on the protein expression of
      extracellular factor (EF). Cluster A contained serotype 1 and 2 isolates that
      were correlated with virulence. Cluster B mainly contained serotype 7 and 9
      isolates. Genetic similarity was observed between serotype 7 and serotype 2
      isolates that do not express muramidase released protein (MRP) and EF (MRP-EF-),
      suggesting these isolates originated from a common founder. Profiles of 25
      putative virulence-associated genes of S. suis were determined among the 55
      isolates. Presence of all 25 genes was shown for cluster A isolates, whereas
      cluster B isolates lacked one or more putative virulence genes. Divergence of S.
      suis isolates was further studied based on the presence of 39 regions of
      difference. Conservation of genes was evaluated by the definition of a core
      genome that contained 78% of all ORFs in P1/7. CONCLUSIONS: In conclusion, we
      show that CGH is a valuable method to study distribution of genes or gene
      clusters among isolates in detail, yielding information on genetic similarity,
      and virulence traits of S. suis isolates.

PMID- 21736720
TI  - Stepped care treatment for depression and anxiety in primary care. a randomized
      controlled trial.
AB  - BACKGROUND: Depressive and anxiety disorders are common in general practice but
      not always treated adequately. Introducing stepped care might improve this. In
      this randomized trial we examined the effectiveness of such a stepped care model.
      METHODS: The study population consisted of primary care attendees aged 18-65
      years with minor or major DSM-IV depressive and/or anxiety disorders, recruited
      through screening. We randomized 120 patients to either stepped care or care as
      usual. The stepped care program consisted of (1) watchful waiting, (2) guided
      self-help, (3) short face-to-face problem solving treatment and (4)
      pharmacotherapy and/or specialized mental health care. Patients were assessed at
      baseline and after 8, 16 and 24 weeks. RESULTS: Symptoms of depression and
      anxiety decreased significantly over time for both groups. However, there was no
      statistically significant difference between the two groups (IDS: P = 0.35 and
      HADS: P = 0.64). The largest, but not significant, effect (d = -0.21) was found
      for anxiety on T3. In both groups approximately 48% of the patients were
      recovered from their DSM-IV diagnosis at the final 6 months assessment.
      CONCLUSIONS: In summary we could not demonstrate that stepped care for depression
      and anxiety in general practice was more effective than care as usual. Possible
      reasons are discussed. TRIAL REGISTRATION: Current Controlled Trails:
      ISRCTN17831610.

PMID- 21736721
TI  - Applicability of the Assessment of Chronic Illness Care (ACIC) instrument in
      Germany resulting in a new questionnaire: questionnaire of chronic illness care
      in primary care.
AB  - BACKGROUND: The Chronic Care Model (CCM) is an evidence based, population based
      approach to improve care for people with chronic conditions. The Assessment of
      Chronic Illness Care (ACIC) instrument is widely used to measure to what extent
      within a healthcare system the CCM is implemented. The aim of this study was to
      translate and culturally adapt the ACIC Instrument for the German healthcare
      system. METHODS: For translating the ACIC instrument, principles of Good Practice
      for the Translation and Cultural Adaptation Process by the ISPOR Task Force were
      followed. Focus groups were additionally conducted with general practitioners to
      adapt the items culturally. RESULTS: The ACIC instrument can not be used in the
      German healthcare system easily due to a multifaceted understanding of words,
      different levels of knowledge of the CCM and fundamental differences between
      health systems. CONCLUSIONS: As following the CCM leads to benefits for patients
      with chronic illnesses, measuring to which extent it is implemented is of major
      interest. A new questionnaire using the CCM as its theoretical basis, sensitive
      to the healthcare systems of the host country has to be created. Knowledge
      transfer between countries by using an instrument from a different healthcare
      system can lead to a completely new questionnaire.

PMID- 21736722
TI  - InN nanorods prepared with CrN nanoislands by plasma-assisted molecular beam
      epitaxy.
AB  - The authors report the influence of CrN nanoisland inserted on growth of
      baseball-bat InN nanorods by plasma-assisted molecular beam epitaxy under In-rich
      conditions. By inserting CrN nanoislands between AlN nucleation layer and the Si
      (111) substrate, it was found that we could reduce strain form Si by inserting
      CrN nanoisland, FWHM of the x-ray rocking curve measured from InN nanorods from
      3,299 reduced to 2,115 arcsec. It is due to the larger strain from lattice miss
      match of the film-like InN structure; however, the strain from lattice miss-match
      was obvious reduced owing to CrN nanoisland inserted. The TEM images confirmed
      the CrN structures and In droplets dissociation from InN, by these results, we
      can speculate the growth mechanism of baseball-bat-like InN nanorods.

PMID- 21736723
TI  - Genomes and geography: genomic insights into the evolution and phylogeography of
      the genus Schistosoma.
AB  - Blood flukes within the genus Schistosoma still remain a major cause of disease
      in the tropics and subtropics and the study of their evolution has been an area
      of major debate and research. With the advent of modern molecular and genomic
      approaches deeper insights have been attained not only into the divergence and
      speciation of these worms, but also into the historic movement of these parasites
      from Asia into Africa, via migration and dispersal of definitive and snail
      intermediate hosts. This movement was subsequently followed by a radiation of
      Schistosoma species giving rise to the S. mansoni and S. haematobium groups, as
      well as the S. indicum group that reinvaded Asia. Each of these major
      evolutionary events has been marked by distinct changes in genomic structure
      evident in differences in mitochondrial gene order and nuclear chromosomal
      architecture between the species associated with Asia and Africa. Data from DNA
      sequencing, comparative molecular genomics and karyotyping are indicative of
      major constitutional genomic events which would have become fixed in the
      ancestral populations of these worms. Here we examine how modern genomic
      techniques may give a more in depth understanding of the evolution of
      schistosomes and highlight the complexity of speciation and divergence in this
      group.

PMID- 21736724
TI  - Acceptance of shared decision making with reference to an electronic library of
      decision aids (arriba-lib) and its association to decision making in patients: an
      evaluation study.
AB  - BACKGROUND: Decision aids based on the philosophy of shared decision making are
      designed to help patients make informed choices among diagnostic or treatment
      options by delivering evidence-based information on options and outcomes. A
      patient decision aid can be regarded as a complex intervention because it
      consists of several presumably relevant components. Decision aids have rarely
      been field tested to assess patients' and physicians' attitudes towards them. It
      is also unclear what effect decision aids have on the adherence to chosen
      options. METHODS: The electronic library of decision aids (arriba-lib) to be used
      within the clinical encounter has a modular structure and contains evidence-based
      decision aids for the following topics: cardiovascular prevention, atrial
      fibrillation, coronary heart disease, oral antidiabetics, conventional and
      intensified insulin therapy, and unipolar depression. We conducted an evaluation
      study in which 29 primary care physicians included 192 patients. After the
      consultation, patients filled in questionnaires and were interviewed via
      telephone two months later. We used generalised estimation equations to measure
      associations within patient variables and traditional crosstab analyses. RESULTS:
      Patients were highly satisfied with arriba-lib and the process of shared decision
      making. Two-thirds of patients reached in the telephone interview wanted to be
      counselled again with arriba-lib. There was a high congruence between preferred
      and perceived decision making. Of those patients reached in the telephone
      interview, 80.7% said that they implemented the decision, independent of gender
      and education. Elderly patients were more likely to say that they implemented the
      decision. CONCLUSIONS: Shared decision making with our multi-modular electronic
      library of decision aids (arriba-lib) was accepted by a high number of patients.
      It has positive associations to general aspects of decision making in patients.
      It can be used for patient groups with a wide range of individual
      characteristics.

PMID- 21736725
TI  - Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely
      correlated with insulin sensitivity in adults.
AB  - BACKGROUND: Accumulating data suggest a novel role for bile acids (BAs) in
      modulating metabolic homeostasis. BA treatment has been shown to improve glucose
      tolerance and to increase energy expenditure in mice. Here, we investigated the
      relationship between fasting plasma BAs concentrations and metabolic parameters
      in humans. FINDINGS: Fasting plasma glucose, insulin and lipid profile were
      measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D), and 22
      non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by
      the determination of the glucose infusion rate (GIR) during a hyperinsulinemic
      euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects).
      Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA),
      chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) concentrations were
      analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a
      positive association was found between HOMA-IR and plasma CDCA (beta = 0.09, p =
      0.001), CA (beta = 0.03, p = 0.09) and DCA concentrations (beta = 0.07, p <
      0.0001). Spearman analysis retrieved an inverse relationship between plasma CDCA
      (r = -0.44, p = 0.03), CA (r = -0.65, p = 0.001) and the GIR. HOMA-IR remained
      positively associated with CDCA (beta = 0.11, p = 0.01), CA (beta = 0.04, p =
      0.01) and DCA (beta = 0.06, p = 0.007) in multivariable analysis, after
      adjustment for age, gender, BMI, HbA1C and plasma lipid parameters. In contrast,
      HbA1c, energy expenditure and plasma lipid concentrations were not correlated
      with plasma BAs levels in multivariable analysis. CONCLUSIONS: Both plasma CDCA,
      CA and DCA concentrations were negatively associated with insulin sensitivity in
      a wide range of subjects.

PMID- 21736726
TI  - The relationship between inotrope exposure, six-hour postoperative physiological
      variables, hospital mortality and renal dysfunction in patients undergoing
      cardiac surgery.
AB  - INTRODUCTION: Acute haemodynamic complications are common after cardiac surgery
      and optimal perioperative use of inotropic agents, typically guided by
      haemodynamic variables, remains controversial. The aim of this study was to
      examine the relationship of inotrope use to hospital mortality and renal
      dysfunction. MATERIAL AND METHODS: A retrospective cohort study of 1,326 cardiac
      surgery patients was carried out at two university-affiliated ICUs. Multivariable
      logistic regression analysis and propensity matching were performed to evaluate
      whether inotrope exposure was independently associated with mortality and renal
      dysfunction. RESULTS: Patients exposed to inotropes had a higher mortality rate
      than those not exposed. After adjusting for differences in Parsonnet score, left
      ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass
      time, reoperation and cardiac index, inotrope exposure appeared to be
      independently associated with increased hospital mortality (adjusted odds ratio
      (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction
      (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis
      similarly demonstrated that death and renal dysfunction were significantly more
      likely to occur in patients exposed to inotropes (P = 0.01). CONCLUSIONS:
      Postoperative inotrope exposure was independently associated with worse outcomes
      in this cohort study. Further research is needed to better elucidate the
      appropriate use of inotropes in cardiac surgery.

PMID- 21736727
TI  - Profiles of family-focused adverse experiences through childhood and early
      adolescence: the ROOTS project a community investigation of adolescent mental
      health.
AB  - BACKGROUND: Adverse family experiences in early life are associated with
      subsequent psychopathology. This study adds to the growing body of work exploring
      the nature and associations between adverse experiences over the childhood years.
      METHODS: Primary carers of 1143 randomly recruited 14-year olds in Cambridgeshire
      and Suffolk, UK were interviewed using the Cambridge Early Experiences Interview
      (CAMEEI) to assess family-focused adversities. Adversities were recorded
      retrospectively in three time periods (early and later childhood and early
      adolescence). Latent Class Analysis (LCA) grouped individuals into adversity
      classes for each time period and longitudinally. Adolescents were interviewed to
      generate lifetime DSM-IV diagnoses using the K-SADS-PL. The associations between
      adversity class and diagnoses were explored. RESULTS: LCA generated a 4-class
      model for each time period and longitudinally. In early childhood 69% were
      allocated to a low adversity class; a moderate adversity class (19%) showed
      elevated rates of family loss, mild or moderate family discord, financial
      difficulties, maternal psychiatric illness and higher risk for paternal atypical
      parenting; a severe class (6%) experienced higher rates on all indicators and
      almost exclusively accounted for incidents of child abuse; a fourth class,
      characterised by atypical parenting from both parents, accounted for the
      remaining 7%. Class membership was fairly stable (~ 55%) over time with escape
      from any adversity by 14 years being uncommon. Compared to those in the low
      class, the odds ratio for reported psychopathology in adolescents in the severe
      class ranged from 8 for disruptive behaviour disorders through to 4.8 for
      depressions and 2.0 for anxiety disorders. Only in the low adversity class did
      significantly more females than males report psychopathology. CONCLUSIONS: Family
      adversities in the early years occur as multiple rather than single experiences.
      Although some children escape adversity, for many this negative family
      environment persists over the first 15 years of life. Different profiles of
      family risk may be associated with specific mental disorders in young people. Sex
      differences in psychopathologies may be most pronounced in those exposed to low
      levels of family adversities.

PMID- 21736728
TI  - Multi-Segment Direct Inject nano-ESI-LTQ-FT-ICR-MS/MS For Protein Identification.
AB  - Reversed phase high performance liquid chromatography (HPLC) interfaced to
      electrospray tandem mass spectrometry (MS/MS) is commonly used for the
      identification of peptides from proteolytically cleaved proteins embedded in a
      polyacrylamide gel matrix as well as for metabolomics screening. HPLC separations
      are time consuming (30-60 min average), costly (columns and mobile phase
      reagents), and carry the risk of column carry over between samples. The use of a
      chip-based nano-ESI platform (Advion NanoMate) based on replaceable nano-tips for
      sample introduction eliminates sample cross-contamination, provides unchanging
      sample matrix, and enhances spray stability with attendant increases in
      reproducibility. Recent papers have established direct infusion nano-ESI-MS/MS
      utilizing the NanoMate for protein identification of gel spots based on full
      range MS scans with data dependent MS/MS. In a full range scan, discontinuous ion
      suppression due to sample matrix can impair identification of putative mass
      features of interest in both the proteomic and metabolomic workflows. In the
      current study, an extension of an established direct inject nano-ESI-MS/MS method
      is described that utilizes the mass filtering capability of an ion-trap for ion
      packet separation into four narrow mass ranges (50 amu overlap) with segment
      specific dynamic data dependent peak inclusion for MS/MS fragmentation (total
      acquisition time of 3 minutes). Comparison of this method with a more traditional
      nanoLC-MS/MS based protocol utilizing solvent/sample stream splitting to achieve
      nanoflow demonstrated comparable results for protein identification from
      polyacrylamide gel matrices. The advantages of this method include full
      automation, lack of cross-contamination, low cost, and high throughput.

PMID- 21736729
TI  - The Patient Enablement Instrument-French version in a family practice setting: a
      reliability study.
AB  - BACKGROUND: Patient enablement can be defined as the extent to which a patient is
      capable of understanding and coping with his or her health issues. This concept
      is linked to a number of health outcomes such as self-management of chronic
      diseases and quality of life. The Patient Enablement Instrument (PEI) was
      designed to measure this concept after a medical consultation. The instrument, in
      its original form and its translations into several languages, has proven to be
      reliable and valid. The purpose of this study was to evaluate the reliability of
      the French version of the PEI (PEI-Fv) in a family practice setting. METHODS: One
      hundred and ten participants were recruited in a family medicine clinic in the
      Saguenay region of Quebec (Canada). The PEI-Fv was completed twice, immediately
      after consultation with a physician (T1) and 2 weeks after the consultation (T2).
      The internal consistency of the tool was assessed with Cronbach's alpha and test
      retest reliability by intraclass correlation coefficient. RESULTS: The mean score
      for the PEI-Fv was 5.06 +/- 3.97 (95% confidence interval [CI]: 4.30-5.81) at T1
      and 4.63 +/- 3.90 (95% CI: 3.82-5.44) at T2. Cronbach's alpha was high at T1
      (alpha1 = 0.93; 95% CI: 0.91-0.95) and T2 (alpha2 = 0.93; 95% CI: 0.91-0.95). The
      intraclass correlation coefficient was 0.62 (95% CI: 0.48-0.74), indicating a
      moderate test-retest reliability. CONCLUSIONS: The internal consistency of the
      PEI-Fv is excellent. Test-retest reliability was moderate to good. Test-retest
      reliability should be examined in further studies at a less than 2-week interval
      to reduce maturation bias. This instrument can be used to measure enablement
      after consultation in a French-speaking family practice setting.

PMID- 21736730
TI  - Protocol for the Cognitive Interventions and Nutritional Supplements (CINS)
      trial: a randomized controlled multicenter trial of a brief intervention (BI)
      versus a BI plus cognitive behavioral treatment (CBT) versus nutritional
      supplements for patients with long-lasting muscle and back pain.
AB  - BACKGROUND: Brief intervention programs are clinically beneficial, and cost
      efficient treatments for low back pain, when offered at 8-12 weeks, compared with
      treatment as usual. However, about 30% of the patients do not return to work. The
      European Guidelines for treatment of chronic low back pain recommends Cognitive
      Behavioral Therapy (CBT), but conclude that further research is needed to
      evaluate the effectiveness of CBT for chronic low back pain. METHODS/DESIGN: The
      aim of the multicenter CINS trial (Cognitive Interventions and Nutritional
      Supplements) is to compare the effectiveness of 4 different interventions; Brief
      Intervention, Brief Intervention and CBT, Brief Intervention and nutritional
      supplements of seal oil, and Brief Intervention and nutritional supplements of
      soy oil. All participants will be randomly assigned to the interventions. The
      nutritional supplements will be tested in a double blind design. 400 patients
      will be recruited from a population of chronic low back pain patients that have
      been sick listed for 2-10 months. Four outpatient clinics, located in different
      parts of Norway, will participate in recruitment and treatment of the
      patients.The Brief Intervention is a one session cognitive, clinical examination
      program based on a non-injury model, where return to normal activity and work is
      the main goal, and is followed by two booster sessions. The CBT is a tailored
      treatment involving 7 sessions, following a detailed manual. The nutritional
      supplements consist of a dosage of 10 grams of either soy or seal oil (capsules)
      per day for 3 months, administered in a double blind design. All patients will be
      followed up with questionnaires after 3, 6 and 12 months, while sick leave data
      will be collected up to at least 24 months after randomization. The primary
      outcome of the study is sick leave and will be based on register data from the
      National Insurance Administration. Secondary outcomes include self-reported data
      on disability, pain, and psychological variables. CONCLUSIONS: To our knowledge,
      the CINS trial will be the largest, randomized trial of psychological and
      nutritional interventions for chronic low back pain patients to date. It will
      provide important information regarding the effectiveness of CBT and seal oil for
      chronic low back pain patients. TRIAL REGISTRATION:
      http://www.clinicaltrials.gov, with registration number NCT00463970.

PMID- 21736731
TI  - Resveratrol inhibits Cdk5 activity through regulation of p35 expression.
AB  - BACKGROUND: We have previously reported that cyclin-dependent kinase 5 (Cdk5)
      participates in the regulation of nociceptive signaling. Through activation of
      the ERK1/2 pathway, Tumor Necrosis Factor-alpha (TNF-alpha) induces expression of
      Egr-1. This results in the sustained and robust expression of p35, a coactivator
      of Cdk5, in PC12 cells, thereby increasing Cdk5 kinase activity. The aim of our
      present study was to test whether resveratrol, a polyphenolic compound with known
      analgesic activity, can regulate Cdk5/p35 activity. RESULTS: Here we used a cell
      based assay in which a p35 promoter-luciferase construct was stably transfected
      in PC12 cells. Our studies demonstrate that resveratrol inhibits p35 promoter
      activity and also blocks the TNF-alpha mediated increase in Cdk5 activity in PC12
      cells. Resveratrol also inhibits p35 expression and blocks the TNF-alpha mediated
      increase in Cdk5 activity in DRG neurons. In the presence of resveratrol, the MEK
      inhibitor decreased p35 promoter activity, whereas the inhibitors of p38 MAPK,
      JNK and NF-kappaB increased p35 promoter activity, indicating that these pathways
      regulate p35 expression differently. The TNF-alpha-mediated increase in Egr-1
      expression was decreased by resveratrol treatment with a concomitant reduction in
      p35 expression and protein levels, resulting in reduced Cdk5 kinase activity.
      CONCLUSIONS: We demonstrate here that resveratrol regulates p35 promoter activity
      in PC12 cells and DRG neurons. Most importantly, resveratrol blocks the TNF-alpha
      mediated increase in p35 promoter activity, thereby reducing p35 expression and
      subsequent Cdk5 kinase activity. This new molecular mechanism adds to the known
      analgesic effects of resveratrol and confirms the need for identifying new
      analgesics based on their ability to inhibit Cdk5 activity for effective
      treatment of pain.

PMID- 21736732
TI  - Generating libraries of iTol2-end insertions at BAC ends using loxP and lox511
      Tn10 transposons.
AB  - BACKGROUND: Bacterial Artificial Chromosomes (BACs) have been widely used as
      transgenes in vertebrate model systems such as mice and zebrafish, for a variety
      of studies. BAC transgenesis has been a powerful tool to study the function of
      the genome, and gene regulation by distal cis-regulatory elements. Recently, BAC
      transgenesis in both mice and zebrafish was further facilitated by development of
      the transposon-mediated method using the Tol2 element. Tol2 ends, in the inverted
      orientation and flanking a 1 kb spacer DNA (iTol2), were introduced into the BAC
      DNA within the bacterial host using recombination of homologous sequences. Here
      we describe experiments designed to determine if a simpler and more flexible
      system could modify BACs so that they would be suitable for transgenesis into
      zebrafish or mouse embryos using the Tol2 transposase. RESULTS: A new technique
      was developed to introduce recognition sequences for the Tol2 transposase into
      BACs in E. coli using the Tn10 transposon vector system. We constructed pTnloxP
      iTol2kan and pTnlox511-iTol2kan to introduce the loxP or lox511 site and iTol2
      cassette, containing the Tol2 cis-sequences in the inverted orientation, into
      BACs that have loxP and lox511 sites flanking genomic DNA inserts by Tn10
      mediated transposition. The procedure enables rapid generation of a large
      collection of BACs ready for transgenesis with the iTol2 cassette at the new end
      of a progressively truncated genomic insert via lox-Cre recombination. The iTol2
      ends are efficiently recognized by the Tol2 transposase, and the BACs readily
      integrate into zebrafish chromosomes. CONCLUSION: The new technology described
      here can rapidly introduce iTol2 ends at a BAC end of choice, and simultaneously
      generate a large collection of BACs with progressive deletions of the genomic DNA
      from that end in a single experiment. This procedure should be applicable to a
      wider variety of BACs containing lox sites flanking the genomic DNA insert,
      including those with sequence repeats. The libraries of iTol2 inserted BACs with
      truncations from an end should facilitate studies on the impact of distal cis
      regulatory sequences on gene function, as well as standard BAC transgenesis with
      precisely trimmed genes in zebrafish or mouse embryos using Tol2 transposition.

PMID- 21736733
TI  - Molecular and cellular correlates of the CIITA-mediated inhibition of HTLV-2 Tax
      2 transactivator function resulting in loss of viral replication.
AB  - BACKGROUND: MHC class II transactivator CIITA inhibits the function of HTLV-2 Tax
      2 viral transactivator and, consequently, the replication of the virus in
      infected cells. Moreover overexpression of the nuclear factor NF-YB, that
      cooperates with CIITA for the expression of MHC class II genes, results also in
      inhibition of Tax-2 transactivation. The purpose of this investigation was to
      assess the cellular and molecular basis of the CIITA-mediated inhibition on Tax
      2, and the relative role of NF-YB in this phenomenon. METHODS: By co
      immunoprecipitation of lysates from 293T cells cotransfected with CIITA or
      fragments of it, and Tax-2 it was assessed whether the two factors interact in
      vivo. A similar approach was used to assess Tax-2-NF-YB interaction. In parallel,
      deletion fragments of CIITA were tested for the inhibition of Tax-2-dependent
      HTLV-2 LTR-luciferase transactivation. Subcellular localization of CIITA and Tax
      2 was investigated by immunofluorescence and confocal microscopy. RESULTS: CIITA
      and Tax-2 interact in vivo through at least two independent regions, at the 1-252
      N-term and at the 410-1130 C-term, respectively. Interestingly only the 1-252 N
      term region mediates Tax-2 functional inhibition. CIITA and Tax-2 are localized
      both in the cytoplasm and in the nucleus, when separately expressed. Instead,
      when coexpressed, most of Tax-2 colocalize with CIITA in cytoplasm and around the
      nuclear membrane. The Tax-2 minor remaining nuclear portion also co-localizes
      with CIITA. Interestingly, when CIITA nucleus-cytoplasm shuttling is blocked by
      leptomycin B treatment, most of the Tax-2 molecules are also blocked and co
      localize with CIITA in the nucleus, suggesting that CIITA-Tax-2 binding does not
      preclude Tax-2 entry into the nucleus.Finally, the nuclear factor NF-YB, also
      strongly binds to Tax-2. Notably, although endogenous NF-YB does not inhibit Tax
      2-dependent HTLV-2 LTR transactivation, it still binds to Tax-2, and in presence
      of CIITA, this binding seems to increase. CONCLUSIONS: These results strongly
      suggest that CIITA inhibit Tax-2 by binding the viral transactivator both
      directly or through a tripartite interaction with NF-YB in. CIITA is therefore a
      viral restriction factor for HTLV-2 and this open the possibility to control HTLV
      2 viral replication and spreading by the controlled induction of CIITA in
      infected cells.

PMID- 21736734
TI  - SR-A ligand and M-CSF dynamically regulate SR-A expression and function in
      primary macrophages via p38 MAPK activation.
AB  - BACKGROUND: Inflammation is characterized by dynamic changes in the expression of
      cytokines, such as M-CSF, and modifications of lipids and proteins that result in
      the formation of ligands for Class A Scavenger Receptors (SR-A). These changes
      are associated with altered SR-A expression in macrophages; however, the
      intracellular signal pathways involved and the extent to which SR-A ligands
      regulate SR-A expression are not well defined. To address these questions, SR-A
      expression and function were examined in resident mouse peritoneal macrophages
      incubated with M-CSF or the selective SR-A ligand acetylated-LDL (AcLDL).
      RESULTS: M-CSF increased SR-A expression and function, and required the specific
      activation of p38 MAPK, but not ERK1/2 or JNK. Increased SR-A expression and
      function returned to basal levels 72 hours after removing M-CSF. We next
      determined whether prolonged incubation of macrophages with SR-A ligand alters SR
      A expression. In contrast to most receptors, which are down-regulated by chronic
      exposure to ligand, SR-A expression was reversibly increased by incubating
      macrophages with AcLDL. AcLDL activated p38 in wild-type macrophages but not in
      SR-A-/- macrophages, and p38 activation was specifically required for AcLDL
      induced SR-A expression. CONCLUSIONS: These results demonstrate that in resident
      macrophages SR-A expression and function can be dynamically regulated by changes
      in the macrophage microenvironment that are typical of inflammatory processes. In
      particular, our results indicate a previously unrecognized role for ligand
      binding to SR-A in up-regulating SR-A expression and activating p38 MAPK. In this
      way, SR-A may modulate inflammatory responses by enhancing macrophage uptake of
      modified protein/lipid, bacteria, and cell debris; and by regulating the
      production of inflammatory cytokines, growth factors, and proteolytic enzymes.

PMID- 21736735
TI  - The influence of mosquito resting behaviour and associated microclimate for
      malaria risk.
AB  - BACKGROUND: The majority of the mosquito and parasite life-history traits that
      combine to determine malaria transmission intensity are temperature sensitive. In
      most cases, the process-based models used to estimate malaria risk and inform
      control and prevention strategies utilize measures of mean outdoor temperature.
      Evidence suggests, however, that certain malaria vectors can spend large parts of
      their adult life resting indoors. PRESENTATION OF HYPOTHESIS: If significant
      proportions of mosquitoes are resting indoors and indoor conditions differ
      markedly from ambient conditions, simple use of outdoor temperatures will not
      provide reliable estimates of malaria transmission intensity. To date, few
      studies have quantified the differential effects of indoor vs outdoor
      temperatures explicitly, reflecting a lack of proper understanding of mosquito
      resting behaviour and associated microclimate. TESTING THE HYPOTHESIS: Published
      records from 8 village sites in East Africa revealed temperatures to be warmer
      indoors than outdoors and to generally show less daily variation. Exploring the
      effects of these temperatures on malaria parasite development rate suggested
      indoor-resting mosquitoes could transmit malaria between 0.3 and 22.5 days
      earlier than outdoor-resting mosquitoes. These differences translate to increases
      in transmission risk ranging from 5 to approaching 3,000%, relative to
      predictions based on outdoor temperatures. The pattern appears robust for low-
      and highland areas, with differences increasing with altitude. IMPLICATIONS OF
      THE HYPOTHESIS: Differences in indoor vs outdoor environments lead to large
      differences in the limits and the intensity of malaria transmission. This finding
      highlights a need to better understand mosquito resting behaviour and the
      associated microclimate, and to broaden assessments of transmission ecology and
      risk to consider the potentially important role of endophily.

PMID- 21736736
TI  - Aggressive low grade middle ear adenocarcinoma with multiple recurrences: a case
      report.
AB  - BACKGROUND: Primary tumours of the middle ear are much less commonly encountered
      in clinical practice than non neoplastic lesions. Middle ear adenocarcinoma is a
      very rare, locally invasive neoplasm assumed to arise from the middle ear mucosa.
      Because the natural course and clinical behavior of this neoplasm are far from
      established, the sporadic reports of such cases continue to provide basis for
      better understanding. CASE DESCRIPTION: A case of low grade adenocarcinoma of the
      middle ear is described in details with regard to its clinical presentation,
      radiological findings, histopathological, immunohistochemical and ultrastructural
      findings. The tumour recurred four times.

PMID- 21736737
TI  - Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired
      odor discrimination in adult mice.
AB  - BACKGROUND: Children whose mothers consumed alcohol during pregnancy exhibit
      widespread brain abnormalities and a complex array of behavioral disturbances.
      Here, we used a mouse model of fetal alcohol exposure to investigate
      relationships between brain abnormalities and specific behavioral alterations
      during adulthood. RESULTS: Mice drank a 10% ethanol solution throughout
      pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high
      resolution MRI to conduct a brain-wide screen for structural changes and found
      that the largest reduction in volume occurred in the olfactory bulbs. Next, we
      tested adult mice in an associative olfactory task and found that fetal alcohol
      exposure impaired discrimination between similar odors but left odor memory
      intact. Finally, we investigated olfactory bulb neurogenesis as a potential
      mechanism by performing an in vitro neurosphere assay, in vivo labeling of new
      cells using BrdU, and in vivo labeling of new cells using a transgenic reporter
      system. We found that fetal alcohol exposure decreased the number of neural
      precursor cells in the subependymal zone and the number of new cells in the
      olfactory bulbs during the first few postnatal weeks. CONCLUSIONS: Using a
      combination of techniques, including structural brain imaging, in vitro and in
      vivo cell detection methods, and behavioral testing, we found that fetal alcohol
      exposure results in smaller olfactory bulbs and impairments in odor
      discrimination that persist into adulthood. Furthermore, we found that these
      abnormalities in olfactory bulb structure and function may arise from deficits in
      the generation of new olfactory bulb neurons during early postnatal development.

PMID- 21736739
TI  - An integrated ChIP-seq analysis platform with customizable workflows.
AB  - BACKGROUND: Chromatin immunoprecipitation followed by next generation sequencing
      (ChIP-seq), enables unbiased and genome-wide mapping of protein-DNA interactions
      and epigenetic marks. The first step in ChIP-seq data analysis involves the
      identification of peaks (i.e., genomic locations with high density of mapped
      sequence reads). The next step consists of interpreting the biological meaning of
      the peaks through their association with known genes, pathways, regulatory
      elements, and integration with other experiments. Although several programs have
      been published for the analysis of ChIP-seq data, they often focus on the peak
      detection step and are usually not well suited for thorough, integrative analysis
      of the detected peaks. RESULTS: To address the peak interpretation challenge, we
      have developed ChIPseeqer, an integrative, comprehensive, fast and user-friendly
      computational framework for in-depth analysis of ChIP-seq datasets. The novelty
      of our approach is the capability to combine several computational tools in order
      to create easily customized workflows that can be adapted to the user's needs and
      objectives. In this paper, we describe the main components of the ChIPseeqer
      framework, and also demonstrate the utility and diversity of the analyses
      offered, by analyzing a published ChIP-seq dataset. CONCLUSIONS: ChIPseeqer
      facilitates ChIP-seq data analysis by offering a flexible and powerful set of
      computational tools that can be used in combination with one another. The
      framework is freely available as a user-friendly GUI application, but all
      programs are also executable from the command line, thus providing flexibility
      and automatability for advanced users.

PMID- 21736738
TI  - Phylogenetic analysis consistent with a clinical history of sexual transmission
      of HIV-1 from a single donor reveals transmission of highly distinct variants.
AB  - BACKGROUND: To combat the pandemic of human immunodeficiency virus 1 (HIV-1), a
      successful vaccine will need to cope with the variability of transmissible
      viruses. Human hosts infected with HIV-1 potentially harbour many viral variants
      but very little is known about viruses that are likely to be transmitted, or even
      if there are viral characteristics that predict enhanced transmission in vivo. We
      show for the first time that genetic divergence consistent with a single
      transmission event in vivo can represent several years of pre-transmission
      evolution. RESULTS: We describe a highly unusual case consistent with a single
      donor transmitting highly related but distinct HIV-1 variants to two individuals
      on the same evening. We confirm that the clustering of viral genetic sequences,
      present within each recipient, is consistent with the history of a single donor
      across the viral env, gag and pol genes by maximum likelihood and bayesian Markov
      Chain Monte Carlo based phylogenetic analyses. Based on an uncorrelated,
      lognormal relaxed clock of env gene evolution calibrated with other datasets, the
      time since the most recent common ancestor is estimated as 2.86 years prior to
      transmission (95% confidence interval 1.28 to 4.54 years). CONCLUSION: Our
      results show that an effective design for a preventative vaccine will need to
      anticipate extensive HIV-1 diversity within an individual donor as well as
      diversity at the population level.

PMID- 21736740
TI  - The concordance of directly and indirectly measured built environment attributes
      and physical activity adoption.
AB  - BACKGROUND: Physical activity (PA) adoption is essential for obesity prevention
      and control, yet ethnic minority women report lower levels of PA and are at
      higher risk for obesity and its comorbidities compared to Caucasians.
      Epidemiological studies and ecologic models of health behavior suggest that built
      environmental factors are associated with health behaviors like PA, but few
      studies have examined the association between built environment attribute
      concordance and PA, and no known studies have examined attribute concordance and
      PA adoption. PURPOSE: The purpose of this study was to associate the degree of
      concordance between directly and indirectly measured built environment attributes
      with changes in PA over time among African American and Hispanic Latina women
      participating in a PA intervention. METHOD: Women (N = 410) completed measures of
      PA at Time 1 (T1) and Time 2 (T2); environmental data collected at T1 were used
      to compute concordance between directly and indirectly measured built environment
      attributes. The association between changes in PA and the degree of concordance
      between each directly and indirectly measured environmental attribute was
      assessed using repeated measures analyses. RESULTS: There were no significant
      associations between built environment attribute concordance values and change in
      self-reported or objectively measured PA. Self-reported PA significantly
      increased over time (F(1,184) = 7.82, p = .006), but this increase did not vary
      by ethnicity or any built environment attribute concordance variable.
      CONCLUSIONS: Built environment attribute concordance may not be associated with
      PA changes over time among minority women. In an effort to promote PA,
      investigators should clarify specific built environment attributes that are
      important for PA adoption and whether accurate perceptions of these attributes
      are necessary, particularly among the vulnerable population of minority women.

PMID- 21736741
TI  - ReadDB provides efficient storage for mapped short reads.
AB  - BACKGROUND: The advent of high-throughput sequencing has enabled sequencing based
      measurements of cellular function, with an individual measurement potentially
      consisting of more than 108 reads. While tools are available for aligning sets of
      reads to genomes and interpreting the results, fewer tools have been developed to
      address the storage and retrieval requirements of large collections of aligned
      datasets. We present ReadDB, a network accessible column store database system
      for aligned high-throughput read datasets. RESULTS: ReadDB stores collections of
      aligned read positions and provides a client interface to support visualization
      and analysis. ReadDB is implemented as a network server that responds to queries
      on genomic intervals in an experiment with either the set of contained reads or a
      histogram based interval summary. Tests on datasets ranging from 105 to 108 reads
      demonstrate that ReadDB performance is generally within a factor of two of local
      storage based methods and often three to five times better than other network
      based methods. CONCLUSIONS: ReadDB is a high-performance foundation for ChIP-Seq
      and RNA-Seq analysis. The client-server model provides convenient access to
      compute cluster nodes or desktop visualization software without requiring a
      shared network filesystem or large amounts of local storage. The client code
      provides a simple interface for fast data access to visualization or analysis.
      ReadDB provides a new way to store genome-aligned reads for use in applications
      where read sequence and alignment mismatches are not needed.

PMID- 21736742
TI  - Resistant starch and exercise independently attenuate weight regain on a high fat
      diet in a rat model of obesity.
AB  - BACKGROUND: Long-term weight reduction remains elusive for many obese
      individuals. Resistant starch (RS) and exercise may be useful for weight
      maintenance. The effects of RS, with or without exercise, on weight regain was
      examined during relapse to obesity on a high carbohydrate, high fat (HC/HF) diet.
      METHODS: Obesity-prone rats were fed ad libitum for 16 weeks then weight reduced
      on a low fat diet to induce a 17% body weight loss (weight reduced rats). Weight
      reduced rats were maintained on an energy-restricted low fat diet for 18 weeks,
      with or without a daily bout of treadmill exercise. Rats were then allowed free
      access to HC/HF diet containing low (0.3%) or high (5.9%) levels of RS. Weight
      regain, energy balance, body composition, adipocyte cellularity, and fuel
      utilization were monitored as rats relapsed to obesity and surpassed their
      original, obese weight. RESULTS: Both RS and exercise independently attenuated
      weight regain by reducing the energy gap between the drive to eat and suppressed
      energy requirements. Exercise attenuated the deposition of lean mass during
      relapse, whereas its combination with RS sustained lean mass accrual as body
      weight returned. Early in relapse, RS lowered insulin levels and reduced the
      deposition of fat in subcutaneous adipose tissue. Exercise cessation at five
      weeks of relapse led to increased weight gain, body fat, subcutaneous adipocytes,
      and decreased lean mass; all detrimental consequences to overall metabolic
      health. CONCLUSIONS: These data are the first to show the complimentary effects
      of dietary RS and regular exercise in countering the metabolic drive to regain
      weight following weight loss and suggest that exercise cessation, in the context
      of relapse on a HC/HF diet, may have dire metabolic consequences.

PMID- 21736743
TI  - Increased local concentration of complement C5a contributes to incisional pain in
      mice.
AB  - BACKGROUND: In our previous study, we demonstrated that local injection of
      complement C5a and C3a produce mechanical and heat hyperalgesia, and that C5a and
      C3a activate and sensitize cutaneous nociceptors in normal skin, suggesting a
      contribution of complement fragments to acute pain. Other studies also have shown
      that the complement system can be activated by surgical incision, and the
      systemic blockade of C5a receptor (C5aR) reduces incision-induced pain and
      inflammation. In this study, we further examined the possible contribution of
      wound area C5a to incisional pain. METHODS: Using of a hind paw incisional model,
      the effects of a selective C5aR antagonist, PMX53, on nociceptive behaviors were
      measured after incision in vivo. mRNA levels of C5 and C5aR in skin, dorsal root
      ganglia (DRG) and spinal cord, and C5a protein levels in the skin were quantified
      after incision. The responses of nociceptors to C5a were also evaluated using the
      in vitro skin-nerve preparation. RESULTS: Local administration of PMX53
      suppressed heat hyperalgesia and mechanical allodynia induced by C5a injection or
      after hind paw incision in vivo. mRNA levels of C5 and C5aR in the skin, but not
      DRG and spinal cord, were dramatically increased after incision. C5a protein in
      the skin was also increased after incision. In vitro C5a did not increase the
      prevalence of fibers with ongoing activity in afferents from incised versus
      control, unincised skin. C5a sensitized C-fiber afferent responses to heat;
      however, this was less evident in afferents adjacent to the incision. PMX53
      blocked sensitization of C-fiber afferents to heat by C5a but did not by itself
      influence ongoing activity or heat sensitivity in afferents innervating control
      or incised skin. The magnitude of mechanical responses was also not affected by
      C5a in any nociceptive fibers innervating incised or unincised skin. CONCLUSIONS:
      This study demonstrates that high locally generated C5a levels are present in
      wounds for at least 72 hours after incision. In skin, C5a contributes to
      hypersensitivity after incision, but increased responsiveness of cutaneous
      nociceptors to C5a was not evident in incised skin. Thus, high local
      concentrations of C5a produced in wounds likely contribute to postoperative pain.

PMID- 21736744
TI  - Single-nucleotide polymorphism discovery by high-throughput sequencing in
      sorghum.
AB  - BACKGROUND: Eight diverse sorghum (Sorghum bicolor L. Moench) accessions were
      subjected to short-read genome sequencing to characterize the distribution of
      single-nucleotide polymorphisms (SNPs). Two strategies were used for DNA library
      preparation. Missing SNP genotype data were imputed by local haplotype
      comparison. The effect of library type and genomic diversity on SNP discovery and
      imputation are evaluated. RESULTS: Alignment of eight genome equivalents (6 Gb)
      to the public reference genome revealed 283,000 SNPs at >=82% confirmation
      probability. Sequencing from libraries constructed to limit sequencing to start
      at defined restriction sites led to genotyping 10-fold more SNPs in all 8
      accessions, and correctly imputing 11% more missing data, than from semirandom
      libraries. The SNP yield advantage of the reduced-representation method was less
      than expected, since up to one fifth of reads started at noncanonical restriction
      sites and up to one third of restriction sites predicted in silico to yield
      unique alignments were not sampled at near-saturation. For imputation accuracy,
      the availability of a genomically similar accession in the germplasm panel was
      more important than panel size or sequencing coverage. CONCLUSIONS: A sequence
      quantity of 3 million 50-base reads per accession using a BsrFI library would
      conservatively provide satisfactory genotyping of 96,000 sorghum SNPs. For most
      reliable SNP-genotype imputation in shallowly sequenced genomes, germplasm panels
      should consist of pairs or groups of genomically similar entries. These results
      may help in designing strategies for economical genotyping-by-sequencing of large
      numbers of plant accessions.

PMID- 21736745
TI  - Bone morphogenetic protein-2 functions as a negative regulator in the
      differentiation of myoblasts, but not as an inducer for the formations of
      cartilage and bone in mouse embryonic tongue.
AB  - BACKGROUND: In vitro studies using the myogenic cell line C2C12 demonstrate that
      bone morphogenetic protein-2 (BMP-2) converts the developmental pathway of C2C12
      from a myogenic cell lineage to an osteoblastic cell lineage. Further, in vivo
      studies using null mutation mice demonstrate that BMPs inhibit the specification
      of the developmental fate of myogenic progenitor cells. However, the roles of
      BMPs in the phases of differentiation and maturation in skeletal muscles have yet
      to be determined. The present study attempts to define the function of BMP-2 in
      the final stage of differentiation of mouse tongue myoblast. RESULTS: Recombinant
      BMP-2 inhibited the expressions of markers for the differentiation of skeletal
      muscle cells, such as myogenin, muscle creatine kinase (MCK), and fast myosin
      heavy chain (fMyHC), whereas BMP-2 siRNA stimulated such markers. Neither the
      recombinant BMP-2 nor BMP-2 siRNA altered the expressions of markers for the
      formation of cartilage and bone, such as osteocalcin, alkaline phosphatase (ALP),
      collagen II, and collagen X. Further, no formation of cartilage and bone was
      observed in the recombinant BMP-2-treated tongues based on Alizarin red and
      Alcian blue stainings. Neither recombinant BMP-2 nor BMP-2 siRNA affected the
      expression of inhibitor of DNA binding/differentiation 1 (Id1). The ratios of
      chondrogenic and osteogenic markers relative to glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH, a house keeping gene) were approximately 1000-fold lower
      than those of myogenic markers in the cultured tongue. CONCLUSIONS: BMP-2
      functions as a negative regulator for the final differentiation of tongue
      myoblasts, but not as an inducer for the formation of cartilage and bone in
      cultured tongue, probably because the genes related to myogenesis are in an
      activation mode, while the genes related to chondrogenesis and osteogenesis are
      in a silencing mode.

PMID- 21736746
TI  - Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk:
      focus on incretins.
AB  - Cardiovascular disease (CVD) risk in type 2 diabetes (T2DM) is only partially
      reduced by intensive glycemic control. Diabetic dyslipidemia is suggested to be
      an additional important contributor to CVD risk in T2DM. Multiple lipid lowering
      medications effectively reduce fasting LDL cholesterol and triglycerides
      concentrations and several of them routinely reduce CVD risk. However, in
      contemporary Western societies the vasculature is commonly exposed to prolonged
      postprandial hyperlipidemia. Metabolism of these postprandial carbohydrates and
      lipids yields multiple proatherogenic products. Even a transient increase in
      these factors may worsen vascular function and induces impaired endothelial
      dependent vasodilatation, a predictor of atherosclerosis and future
      cardiovascular events. There is a recent increased appreciation for the role of
      gut-derived incretin hormones in controlling the postprandial metabolic milieu.
      Incretin-based medications have been developed and are now used to control
      postprandial hyperglycemia in T2DM. Recent data indicate that these medications
      may also have profound effects on postprandial lipid metabolism and may favorably
      influence several cardiovascular functions. This review discusses (1) the
      postprandial state with special emphasis on postprandial lipid metabolism and its
      role in endothelial dysfunction and cardiovascular risk, (2) the ability of
      incretins to modulate postprandial hyperlipidemia and (3) the potential of
      incretin-based therapeutic strategies to improve vascular function and reduce CVD
      risk.

PMID- 21736747
TI  - Circulating adiponectin levels are lower in Latino versus non-Latino white
      patients at risk for cardiovascular disease, independent of adiposity measures.
AB  - BACKGROUND: Latinos in the United States have a higher prevalence of type 2
      diabetes than non-Latino whites, even after controlling for adiposity. Decreased
      adiponectin is associated with insulin resistance and predicts T2DM, and
      therefore may mediate this ethnic difference. We compared total and high
      molecular-weight (HMW) adiponectin in Latino versus white individuals, identified
      factors associated with adiponectin in each ethnic group, and measured the
      contribution of adiponectin to ethnic differences in insulin resistance. METHODS:
      We utilized cross-sectional data from subjects in the Latinos Using Cardio Health
      Actions to reduce Risk study. Participants were Latino (n = 119) and non-Latino
      white (n = 60) men and women with hypertension and at least one other risk factor
      for CVD (age 61 +/- 10 yrs, 49% with T2DM), seen at an integrated community
      health and hospital system in Denver, Colorado. Total and HMW adiponectin was
      measured by RIA and ELISA respectively. Fasting glucose and insulin were used to
      calculate the homeostasis model insulin resistance index (HOMA-IR). Variables
      independently associated with adiponectin levels were identified by linear
      regression analyses. Adiponectin's contribution to ethnic differences in insulin
      resistance was assessed in multivariate linear regression models of Latino
      ethnicity, with logHOMA-IR as a dependent variable, adjusting for possible
      confounders including age, gender, adiposity, and renal function. RESULTS: Mean
      adiponectin levels were lower in Latino than white patients (beta estimates: -4.5
      (-6.4, -2.5), p < 0.001 and -1.6 (-2.7, -0.5), p < 0.005 for total and HMW
      adiponectin), independent of age, gender, BMI/waist circumference,
      thiazolidinedione use, diabetes status, and renal function. An expected negative
      association between adiponectin and waist circumference was seen among women and
      non-Latino white men, but no relationship between these two variables was
      observed among Latino men. Ethnic differences in logHOMA-IR were no longer
      observed after controlling for adiponectin levels. CONCLUSIONS: Among patients
      with CVD risk, total and HMW adiponectin is lower in Latinos, independent of
      adiposity and other known regulators of adiponectin. Ethnic differences in
      adiponectin regulation may exist and future research in this area is warranted.
      Adiponectin levels accounted for the observed variability in insulin resistance,
      suggesting a contribution of decreased adiponectin to insulin resistance in
      Latino populations.

PMID- 21736748
TI  - Current european regulatory perspectives on insulin analogues.
AB  - Insulin analogues are increasingly considered as an alternative to human insulin
      in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically
      different from human insulin and may have different pharmacokinetic or
      pharmacodynamic properties. The significance of the modifications of the insulin
      molecule for the safety profile of IAs must be considered. This review describes
      the regulatory procedure and the expectations for the scientific content of
      European marketing authorization applications for innovative IAs submitted to the
      European Medicines Agency. Particular consideration is given to a potential
      cancer hazard. Specific regulatory guidance on how to address a possible
      carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies
      is available. After marketing authorization, the factual access of patients to
      the new product will be determined to great extent by health technology
      assessment bodies, reimbursement decisions and the price. Whereas the marketing
      authorization is a European decision, pricing and reimbursement are national or
      regional responsibilities. The assessment of benefit and risk by the European
      Medicines Agency is expected to influence future decisions on price and
      reimbursement on a national or regional level. Collaborations between regulatory
      agencies and health technology assessment bodies have been initiated on European
      and national level to facilitate the use of the European Medicines Agency's
      benefit risk assessment as basis on which to build the subsequent health
      technology assessment. The option for combined or joint scientific advice
      procedures with regulators and health technology assessment bodies on European
      level or on a national level in several European Member States may help
      applicants to optimize their development program and dossier preparation in
      regard of both European marketing authorization application and reimbursement
      decisions.

PMID- 21736749
TI  - Meta-analysis of multiple microarray datasets reveals a common gene signature of
      metastasis in solid tumors.
AB  - BACKGROUND: Metastasis is the number one cause of cancer deaths. Expression
      microarrays have been widely used to study metastasis in various types of cancer.
      We hypothesize that a meta-analysis of publicly available gene expression
      datasets in various tumor types can identify a signature of metastasis that is
      common to multiple tumor types. This common signature of metastasis may help us
      to understand the shared steps in the metastatic process and identify useful
      biomarkers that could predict metastatic risk. METHODS: We identified 18 publicly
      available gene expression datasets in the Oncomine database comparing distant
      metastases to primary tumors in various solid tumors which met our eligibility
      criteria. We performed a meta-analysis using a modified permutation counting
      method in order to obtain a common gene signature of metastasis. We then
      validated this signature in independent datasets using gene set expression
      comparison analysis with the LS-statistic. RESULTS: A common metastatic signature
      of 79 genes was identified in the metastatic lesions compared with primaries with
      a False Discovery Proportion of less than 0.1. Interestingly, all the genes in
      the signature, except one, were significantly down-regulated, suggesting that
      overcoming metastatic suppression may be a key feature common to all metastatic
      tumors. Pathway analysis of the significant genes showed that the genes were
      involved in known metastasis-associated pathways, such as integrin signaling,
      calcium signaling, and VEGF signaling. To validate the signature, we used an
      additional six expression datasets that were not used in the discovery study. Our
      results showed that the signature was significantly enriched in four validation
      sets with p-values less than 0.05. CONCLUSIONS: We have modified a previously
      published meta-analysis method and identified a common metastatic signature by
      comparing primary tumors versus metastases in various tumor types. This approach,
      as well as the gene signature identified, provides important insights to the
      common metastatic process and a foundation for future discoveries that could have
      broad application, such as drug discovery, metastasis prediction, and mechanistic
      studies.

PMID- 21736750
TI  - Outdoor host seeking behaviour of Anopheles gambiae mosquitoes following
      initiation of malaria vector control on Bioko Island, Equatorial Guinea.
AB  - BACKGROUND: Indoor-based anti-vector interventions remain the preferred means of
      reducing risk of malaria transmission in malaria endemic areas around the world.
      Despite demonstrated success in reducing human-mosquito interactions, these
      methods are effective solely against endophilic vectors. It may be that outdoor
      locations serve as an important venue of host seeking by Anopheles gambiae sensu
      lato (s.l.) mosquitoes where indoor vector suppression measures are employed.
      This paper describes the host seeking activity of anopheline mosquito vectors in
      the Punta Europa region of Bioko Island, Equatorial Guinea. In this area, An.
      gambiae sensu stricto (s.s.) is the primary malaria vector. The goal of the paper
      is to evaluate the importance of An gambiae s.l. outdoor host seeking behaviour
      and discuss its implications for anti-vector interventions. METHODS: The venue
      and temporal characteristics of host seeking by anopheline vectors in a
      hyperendemic setting was evaluated using human landing collections conducted
      inside and outside homes in three villages during both the wet and dry seasons in
      2007 and 2008. Additionally, five bi-monthly human landing collections were
      conducted throughout 2009. Collections were segregated hourly to provide a time
      distribution of host-seeking behaviour. RESULTS: Surprisingly high levels of
      outdoor biting by An. gambiae senso stricto and An. melas vectors were observed
      throughout the night, including during the early evening and morning hours when
      human hosts are often outdoors. As reported previously, An. gambiae s.s. is the
      primary malaria vector in the Punta Europa region, where it seeks hosts outdoors
      at least as much as it does indoors. Further, approximately 40% of An. gambiae
      s.l. are feeding at times when people are often outdoors, where they are not
      protected by IRS or LLINs. Repeated sampling over two consecutive dry-wet season
      cycles indicates that this result is independent of seasonality. CONCLUSIONS: An.
      gambiae s.l. mosquitoes currently seek hosts in outdoor venues as much as indoors
      in the Punta Europa region of Bioko Island. This contrasts with an earlier pre
      intervention observation of exclusive endophagy of An. gambiae in this region. In
      light of this finding, it is proposed that the long term indoor application of
      insecticides may have resulted in an adaptive shift toward outdoor host seeking
      in An. gambiae s.s. on Bioko Island.

PMID- 21736751
TI  - Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in
      rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study.
AB  - BACKGROUND: Canakinumab is a fully human anti-interleukin IL-1beta monoclonal
      antibody, being investigated for the treatment of rheumatoid arthritis (RA). This
      multicenter, phase II, randomized, double-blind, placebo-controlled, parallel
      group, dose-finding study investigated the efficacy and safety of canakinumab in
      patients with active RA despite ongoing therapy at stable doses of methotrexate.
      METHODS: Patients were randomized to receive one of four regimens, in addition to
      methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks
      (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg
      intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or
      placebo SC every 2 weeks. RESULTS: Among 274 patients with evaluable efficacy
      data, the percentage of responders according to American College of Rheumatology
      50 criteria (the primary endpoint, based on a 28-joint count) was significantly
      higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%,
      respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was
      also associated with significantly more favorable responses at week 12 with
      respect to secondary endpoints including the Disease Activity Score 28, scores on
      the Health Assessment Questionnaire and Functional Assessment of Chronic Illness
      Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global
      assessments of disease activity. No safety concerns were raised with canakinumab
      therapy, particularly with regard to infections. Few injection-site reactions
      occurred. CONCLUSION: The addition of canakinumab 150 mg SC q4wk improves
      therapeutic responses among patients who have active RA despite stable treatment
      with methotrexate. TRIAL REGISTRATION: (ClinicalTrials.gov identifier:
      NCT00784628).

PMID- 21736752
TI  - In vitro anti-inflammatory and anti-coagulant effects of antibiotics towards
      Platelet Activating Factor and thrombin.
AB  - BACKGROUND: Sepsis is characterized as a systemic inflammatory response that
      results from the inability of the immune system to limit bacterial spread during
      an ongoing infection. In this condition the significant mediator of inflammation
      Platelet Activating Factor (PAF) and the coagulant factor thrombin are
      implicated. In animal models, treatment with PAF-antagonists or co-administration
      of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited
      promising results. In order to examine the putative anti-inflammatory and/or
      antithrombotic interactions between antibiotic treatment used in sepsis with PAF
      and/or thrombin, we studied the in vitro effects of these compounds towards PAF
      or/and thrombin related activities and towards PAF basic metabolic enzymes.
      METHODS: We assessed the inhibitory effect of these drugs against PAF or thrombin
      induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach
      Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on
      Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF
      AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key
      enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation,
      respectively. RESULTS: Several antibiotics inhibited PAF-induced platelet
      aggregation of both WRPs and rPRP in a concentration-depended manner, with
      clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory
      effect, while when combined they synergistically inhibited PAF. Higher
      concentrations of all antibiotics tested were needed in order to inhibit PAF
      induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of
      WRPs. Concentrations of these drugs similar to their IC50 values against PAF
      activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of
      rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit
      plasma-PAF-AH activity. CONCLUSIONS: These newly found properties of antibiotics
      used in sepsis suggest that apart from their general actions, these drugs may
      present additional beneficial anti-inflammatory and anti-coagulant effects
      against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor
      and/or the thrombin/protease-activated-receptor-1 systems, and/or by reducing PAF
      levels through both PAF-biosynthesis inhibition and PAF-catabolism induction.
      These promising in vitro results need to be further studied and confirmed by in
      vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis.

PMID- 21736753
TI  - Evolving hard problems: Generating human genetics datasets with a complex
      etiology.
AB  - BACKGROUND: A goal of human genetics is to discover genetic factors that
      influence individuals' susceptibility to common diseases. Most common diseases
      are thought to result from the joint failure of two or more interacting
      components instead of single component failures. This greatly complicates both
      the task of selecting informative genetic variants and the task of modeling
      interactions between them. We and others have previously developed algorithms to
      detect and model the relationships between these genetic factors and disease.
      Previously these methods have been evaluated with datasets simulated according to
      pre-defined genetic models. RESULTS: Here we develop and evaluate a model free
      evolution strategy to generate datasets which display a complex relationship
      between individual genotype and disease susceptibility. We show that this model
      free approach is capable of generating a diverse array of datasets with distinct
      gene-disease relationships for an arbitrary interaction order and sample size. We
      specifically generate eight-hundred Pareto fronts; one for each independent run
      of our algorithm. In each run the predictiveness of single genetic variation and
      pairs of genetic variants have been minimized, while the predictiveness of third,
      fourth, or fifth-order combinations is maximized. Two hundred runs of the
      algorithm are further dedicated to creating datasets with predictive four or five
      order interactions and minimized lower-level effects. CONCLUSIONS: This method
      and the resulting datasets will allow the capabilities of novel methods to be
      tested without pre-specified genetic models. This allows researchers to evaluate
      which methods will succeed on human genetics problems where the model is not
      known in advance. We further make freely available to the community the entire
      Pareto-optimal front of datasets from each run so that novel methods may be
      rigorously evaluated. These 76,600 datasets are available from
      http://discovery.dartmouth.edu/model_free_data/.

PMID- 21736754
TI  - Does maternal oral health predict child oral health-related quality of life in
      adulthood?
AB  - BACKGROUND: A parental/family history of poor oral health may influence the oral
      health-related quality of life (OHRQOL) of adults. OBJECTIVES: To determine
      whether the oral health of mothers of young children can predict the OHRQOL of
      those same children when they reach adulthood. METHODS: Oral examination and
      interview data from the Dunedin Study's age-32 assessment, as well as maternal
      self-rated oral health data from the age-5 assessment were used. The main outcome
      measure was study members' short-form Oral Health Impact Profile (OHIP-14) at age
      32. Analyses involved 827 individuals (81.5% of the surviving cohort) dentally
      examined at both ages, who also completed the OHIP-14 questionnaire at age 32,
      and whose mothers were interviewed at the age-5 assessment. RESULTS: There was a
      consistent gradient of relative risk across the categories of maternal self-rated
      oral health status at the age-5 assessment for having one or more impacts in the
      overall OHIP-14 scale, whereby risk was greatest among the study members whose
      mothers rated their oral health as "poor/edentulous", and lowest among those with
      an "excellent/fairly good" rating. In addition, there was a gradient in the age
      32 mean OHIP-14 score, and in the mean number of OHIP-14 impacts at age 32 across
      the categories of maternal self-rated oral health status. The higher risk of
      having one or more impacts in the psychological discomfort subscale, when mother
      rated her oral health as "poor/edentulous", was statistically significant.
      CONCLUSIONS: These data suggest that maternal self-rated oral health when a child
      is young has a bearing on that child's OHRQOL almost three decades later. The
      adult offspring of mothers with poor self-rated oral health had poorer OHRQOL
      outcomes, particularly in the psychological discomfort subscale.

PMID- 21736755
TI  - A genetic linkage map and comparative mapping of the prairie vole (Microtus
      ochrogaster) genome.
AB  - BACKGROUND: The prairie vole (Microtus ochrogaster) is an emerging rodent model
      for investigating the genetics, evolution and molecular mechanisms of social
      behavior. Though a karyotype for the prairie vole has been reported and low
      resolution comparative cytogenetic analyses have been done in this species, other
      basic genetic resources for this species, such as a genetic linkage map, are
      lacking. RESULTS: Here we report the construction of a genome-wide linkage map of
      the prairie vole. The linkage map consists of 406 markers that are spaced on
      average every 7 Mb and span an estimated ~90% of the genome. The sex average
      length of the linkage map is 1707 cM, which, like other Muroid rodent linkage
      maps, is on the lower end of the length distribution of linkage maps reported to
      date for placental mammals. Linkage groups were assigned to 19 out of the 26
      prairie vole autosomes as well as the X chromosome. Comparative analyses of the
      prairie vole linkage map based on the location of 387 Type I markers identified
      61 large blocks of synteny with the mouse genome. In addition, the results of the
      comparative analyses revealed a potential elevated rate of inversions in the
      prairie vole lineage compared to the laboratory mouse and rat. CONCLUSIONS: A
      genetic linkage map of the prairie vole has been constructed and represents the
      fourth genome-wide high-resolution linkage map reported for Muroid rodents and
      the first for a member of the Arvicolinae sub-family. This resource will advance
      studies designed to dissect the genetic basis of a variety of social behaviors
      and other traits in the prairie vole as well as our understanding of genome
      evolution in the genus Microtus.

PMID- 21736756
TI  - The Hirsch index - a play on numbers or a true appraisal of academic output?
AB  - Citation metrics have rapidly gained importance in today's landscape and are
      being increasingly utilized as a yardstick in making several important decisions
      regarding academic funding and appointments. The impact factor has traditionally
      been the metric most often employed in this regard. However, the emergence of the
      Hirsch index has provided an alternative to the impact factor. The h-index,
      despite its flaws, continues to gain acceptance and popularity in the medical
      community. Several medical journals have evaluated and endorsed the use of the h
      index. However, it must be interpreted with all of its limitations in mind.

PMID- 21736757
TI  - Validity of parent-reported weight and height of preschool children measured at
      home or estimated without home measurement: a validation study.
AB  - BACKGROUND: Parental reports are often used in large-scale surveys to assess
      children's body mass index (BMI). Therefore, it is important to know to what
      extent these parental reports are valid and whether it makes a difference if the
      parents measured their children's weight and height at home or whether they
      simply estimated these values. The aim of this study is to compare the validity
      of parent-reported height, weight and BMI values of preschool children (3-7 y
      old), when measured at home or estimated by parents without actual measurement.
      METHODS: The subjects were 297 Belgian preschool children (52.9% male).
      Participation rate was 73%. A questionnaire including questions about height and
      weight of the children was completed by the parents. Nurses measured height and
      weight following standardised procedures. International age- and sex-specific BMI
      cut-off values were employed to determine categories of weight status and
      obesity. RESULTS: On the group level, no important differences in accuracy of
      reported height, weight and BMI were identified between parent-measured or
      estimated values. However, for all 3 parameters, the correlations between
      parental reports and nurse measurements were higher in the group of children
      whose body dimensions were measured by the parents. Sensitivity for underweight
      and overweight/obesity were respectively 73% and 47% when parents measured their
      child's height and weight, and 55% and 47% when parents estimated values without
      measurement. Specificity for underweight and overweight/obesity were respectively
      82% and 97% when parents measured the children, and 75% and 93% with parent
      estimations. CONCLUSIONS: Diagnostic measures were more accurate when parents
      measured their child's weight and height at home than when those dimensions were
      based on parental judgements. When parent-reported data on an individual level is
      used, the accuracy could be improved by encouraging the parents to measure weight
      and height of their children at home.

PMID- 21736758
TI  - Modular hybrid total hip arthroplasty. Experimental study in dogs.
AB  - BACKGROUND: This prospective experimental study evaluated the surgical procedure
      and results of modular hybrid total hip arthroplasty in dogs. METHODS: Ten
      skeletally mature healthy mongrel dogs with weights varying between 19 and 27 kg
      were used. Cemented modular femoral stems and uncemented porous-coated acetabular
      cups were employed. Clinical and radiographic evaluations were performed before
      surgery and at 30, 60, 90, 120, 180 and 360 days post-operation. RESULTS:
      Excellent weight bearing was noticed in the operated limb in seven dogs.
      Dislocation followed by loosening of the prosthesis was noticed in two dogs,
      which were therefore properly treated with a femoral head osteotomy. Femoral
      fracture occurred in one dog, which was promptly treated with full implant
      removal and femoral osteosynthesis. CONCLUSIONS: The canine modular hybrid total
      hip arthroplasty provided excellent functionality of the operated limb.

PMID- 21736759
TI  - The differential disease regulome.
AB  - BACKGROUND: Transcription factors in disease-relevant pathways represent
      potential drug targets, by impacting a distinct set of pathways that may be
      modulated through gene regulation. The influence of transcription factors is
      typically studied on a per disease basis, and no current resources provide a
      global overview of the relations between transcription factors and disease.
      Furthermore, existing pipelines for related large-scale analysis are tailored for
      particular sources of input data, and there is a need for generic methodology for
      integrating complementary sources of genomic information. RESULTS: We here
      present a large-scale analysis of multiple diseases versus multiple transcription
      factors, with a global map of over-and under-representation of 446 transcription
      factors in 1010 diseases. This map, referred to as the differential disease
      regulome, provides a first global statistical overview of the complex
      interrelationships between diseases, genes and controlling elements. The map is
      visualized using the Google map engine, due to its very large size, and provides
      a range of detailed information in a dynamic presentation format.The analysis is
      achieved through a novel methodology that performs a pairwise, genome-wide
      comparison on the cartesian product of two distinct sets of annotation tracks,
      e.g. all combinations of one disease and one TF.The methodology was also used to
      extend with maps using alternative data sets related to transcription and
      disease, as well as data sets related to Gene Ontology classification and histone
      modifications. We provide a web-based interface that allows users to generate
      other custom maps, which could be based on precisely specified subsets of
      transcription factors and diseases, or, in general, on any categorical genome
      annotation tracks as they are improved or become available. CONCLUSION: We have
      created a first resource that provides a global overview of the complex relations
      between transcription factors and disease. As the accuracy of the disease
      regulome depends mainly on the quality of the input data, forthcoming ChIP-seq
      based binding data for many TFs will provide improved maps. We further believe
      our approach to genome analysis could allow an advance from the current typical
      situation of one-time integrative efforts to reproducible and upgradable
      integrative analysis. The differential disease regulome and its associated
      methodology is available at http://hyperbrowser.uio.no.

PMID- 21736760
TI  - Are risk estimates biased in follow-up studies of psychosocial factors with low
      base-line participation?
AB  - BACKGROUND: Low participation in population-based follow-up studies addressing
      psychosocial risk factors may cause biased estimation of health risk but the
      issue has seldom been examined. We compared risk estimates for selected health
      outcomes among respondents and the entire source population. METHODS: In a Danish
      cohort study of associations between psychosocial characteristics of the work
      environment and mental health, the source population of public service workers
      comprised 10,036 employees in 502 work units of which 4,489 participated
      (participation rate 45%). Data on the psychosocial work environment were obtained
      for each work unit by calculating the average of the employee self-reports. The
      average values were assigned all employees and non-respondent at the work unit.
      Outcome data on sick leave and prescription of antidepressant medication during
      the follow-up period (1.4.2007-31.12.2008) was obtained by linkage to national
      registries. RESULTS: Respondents differed at baseline from non-respondents by
      gender, age, employment status, sick leave and hospitalization for affective
      disorders. However, risk estimates for sick leave and prescription of
      antidepressant medication, during follow-up, based on the subset of participants,
      did only differ marginally from risk estimates based upon the entire population.
      CONCLUSIONS: We found no indications that low participation at baseline distorts
      the estimates of associations between the work unit level of psychosocial work
      environment and mental health outcomes during follow-up. These results may not be
      valid for other exposures or outcomes.

PMID- 21736761
TI  - Atypical Burkitt's lymphoma transforming from follicular lymphoma.
AB  - Amongst follicular lymphoma that transforms into a high-grade lymphoma, majority
      are diffuse large B cell lymphoma. Here we reported a rare atypical Burkitt's
      lymphoma transformation from an asymptomatic follicular lymphoma. Lymph node
      biopsy showed a composite lymphoma with infiltration of the inter-follicular
      areas by high grade small non-cleaved lymphoma cells amongst neoplastic
      follicles. Moreover, FISH and molecular genetic study confirmed concomitant MYC
      translocations and t(14;18) in the high-grade component, thereby suggesting the
      transformation of atypical Burkitt's lymphoma from an undiagnosed antecedent
      follicular lymphoma. The disease followed an aggressive clinical course,
      terminating in refractory disease 13 months after diagnosis. This is followed by
      a comprehensive review of the literature on lymphoma transformations from
      underlying follicular lymphoma after acquisition of MYC translocation, using
      Burkitt's lymphoma, follicular lymphoma, transformation and MYC translocations as
      keywords.

PMID- 21736762
TI  - Protocol of a randomized controlled trial of culturally sensitive interventions
      to improve African Americans' and non-African Americans' early, shared, and
      informed consideration of live kidney transplantation: the Talking About Live
      Kidney Donation (TALK) Study.
AB  - BACKGROUND: Live kidney transplantation (LKT) is underutilized, particularly
      among ethnic/racial minorities. The effectiveness of culturally sensitive
      educational and behavioral interventions to encourage patients' early, shared
      (with family and health care providers) and informed consideration of LKT and
      ameliorate disparities in consideration of LKT is unknown. METHODS/DESIGN: We
      report the protocol of the Talking About Live Kidney Donation (TALK) Study, a two
      phase study utilizing qualitative and quantitative research methods to design and
      test culturally sensitive interventions to improve patients' shared and informed
      consideration of LKT. Study Phase 1 involved the evidence-based development of
      culturally sensitive written and audiovisual educational materials as well as a
      social worker intervention to encourage patients' engagement in shared and
      informed consideration of LKT. In Study Phase 2, we are currently conducting a
      randomized controlled trial in which participants with progressing chronic kidney
      disease receive: 1) usual care by their nephrologists, 2) usual care plus the
      educational materials, or 3) usual care plus the educational materials and the
      social worker intervention. The primary outcome of the randomized controlled
      trial will include patients' self-reported rates of consideration of LKT
      (including family discussions of LKT, patient-physician discussions of LKT, and
      identification of an LKT donor). We will also assess differences in rates of
      consideration of LKT among African Americans and non-African Americans.
      DISCUSSION: The TALK Study rigorously developed and is currently testing the
      effectiveness of culturally sensitive interventions to improve patients' and
      families' consideration of LKT. Results from TALK will provide needed evidence on
      ways to enhance consideration of this optimal treatment for patients with end
      stage renal disease. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00932334.

PMID- 21736763
TI  - Target drug delivery system as a new scarring modulation after glaucoma
      filtration surgery.
AB  - BACKGROUND: Excessive wound healing following glaucoma filtration surgery is the
      main determinant of surgical failure, resulting from the activation of human
      Tenon's capsule fibroblasts (HTFs). To mitigate the excessive wound healing, the
      topic all use of antiproliferative agents, such as mitomycin C (MMC) and 5
      fluorouracil (5-FU), has increased the surgery success rate, but the traditional
      administration of these agents can result in a variety of toxicities with
      nonspecific damage. However, modulation of the wound healing process to prevent
      excessive fibroblast proliferation and scar formation can play a major role in
      improving the outcome of surgery. Therefore, the search for alternative modes of
      drug delivery and new agents is needed to minimize the ocular complications and
      improve the success of surgery. We have shown that there is a postoperative over
      expression of the LDL receptor (LDLr) in the activated HTFs may provide a novel
      target for drug delivery systems. PRESENTATION OF THE HYPOTHESIS: We hypothesize
      that anti fibrotic agents (MMC) encapsulated in LDLr targeting drug delivery
      system (LDL-MMC-chitosan nanoparticles) may be proposed in anti-scarring therapy
      to increase the safety and effectiveness and to reduce toxicity. TESTING THE
      HYPOTHESIS: A chitosan-based polymeric predrug of MMC was synthesized and its
      cytotoxicity was proved to be low. In addition, we propose hyaluronic acid film
      as a container to release LDL-MMC-chitosan nanoparticles gradually at
      subconjunctival filtering site after glaucoma filtration surgery to eliminate the
      LDL-MMC-chitosan nanoparticles. IMPLICATIONS OF THE HYPOTHESIS AND DISCUSSION:
      This strategy can be applicable to anti-scarring therapy during excessive
      conjunctival wound healing. This hypothesis integrates advantages of the
      targeting drug delivery and anti fibrotic agents, such as high efficiency,
      convenience, and lower the toxicity.

PMID- 21736764
TI  - Chronic prostatitis.
AB  - INTRODUCTION: Chronic prostatitis can cause pain and urinary symptoms, and
      usually occurs without positive bacterial cultures from prostatic secretions
      (known as chronic abacterial prostatitis or chronic pelvic pain syndrome
      [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation,
      but the cause and natural history of CP/CPPS are unknown. METHODS AND OUTCOMES:
      We conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of treatments for chronic bacterial prostatitis?
      What are the effects of treatments for chronic abacterial prostatitis/chronic
      pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library, and
      other important databases up to August 2010 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 33 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: 5 alpha-reductase inhibitors, allopurinol,
      alpha-blockers, biofeedback, local injections of antimicrobial drugs,
      mepartricin, non-steroidal anti-inflammatory drugs (NSAIDs), oral antimicrobial
      drugs, pentosan polysulfate, prostatic massage, quercetin, radical prostatectomy,
      sitz baths, transurethral microwave thermotherapy, and transurethral resection.

PMID- 21736765
TI  - Uveitis (acute anterior).
AB  - INTRODUCTION: Anterior uveitis is rare, with an annual incidence of 12/100,000
      population, although it is more common in Finland (annual incidence of
      23/100,000), probably because of genetic factors, such as high frequency of HLA
      B27 in the population. It is often self-limiting, but can, in some cases, lead to
      complications such as posterior synechiae, cataract, glaucoma, and chronic
      uveitis. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
      answer the following clinical question: What are the effects of anti-inflammatory
      eye drops on acute anterior uveitis? We searched: Medline, Embase, The Cochrane
      Library and other important databases up to November 2009 (Clinical Evidence
      reviews are updated periodically, please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found six
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions:
      corticosteroids, mydriatics, and non-steroidal anti-inflammatory drug eye drops.

PMID- 21736766
TI  - Soya protein attenuates abnormalities of the renin-angiotensin system in adipose
      tissue from obese rats.
AB  - Several metabolic disturbances during obesity are associated with adipose tissue
      altered functions. Adipocytes contain the renin-angiotensin system (RAS), which
      regulates signalling pathways that control angiogenesis via Akt in an autocrine
      fashion. Soya protein (Soy) consumption modifies the gene expression pattern in
      adipose tissue, resulting in an improved adipocyte function. Therefore, the aim
      of the present work is to study whether dietary Soy regulates the expression of
      RAS and angiogenesis-related genes and its association with the phosphorylated
      state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or
      casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied
      in the adipose tissue, and Akt phosphorylation and hormone release were measured
      in the primary adipocyte culture. The present results show that Soy treatment in
      comparison with Cas consumption induces lower angiotensin release and increased
      insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption
      varies the expression of RAS and angiogenesis-related genes, which maintain cell
      size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus,
      adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in
      dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken
      together, these findings suggest that Soy can be used as a dietary strategy to
      preserve adipocyte functionality and to prevent obesity abnormalities.

PMID- 21736767
TI  - Effect of fast dietary proteins on muscle protein synthesis rate and muscle
      strength in ad libitum-fed and energy-restricted old rats.
AB  - Sarcopenia is defined as age-related loss of muscle mass and strength. Energy
      restriction (ER) delays fibre loss by limiting the accumulated deleterious
      effects of reactive oxygen species on muscle. However, insufficient protein
      intake during ER might affect muscle mass and function. We hypothesised that
      ingestion of fast-digested proteins such as whey protein (WP) improves muscle
      protein synthesis and muscle strength in aged ER rats. The effect of WP or casein
      (CAS, slow protein) on muscle mass, protein synthesis and strength was evaluated
      in 21-month-old rats fed for 5 months either ad libitum (AL) or a 40 % protein
      and energy-restricted (PER) or 40 % AL-isonitrogenous ER diet. The nitrogen
      balance was reduced in PER-CAS rats only ( - 48 % v. AL-CAS). WP stimulated
      muscle protein synthesis rates compared with CAS in all groups (+21,+37 and +34 %
      in AL, PER and ER conditions, respectively). Muscle strength was higher in ER
      rats than in AL rats (+23 and +12 % for WP or CAS, respectively). Muscle
      performance tended to be greater in ER rats fed WP than in ER-CAS rats (P <
      0.09). In conclusion, we observed that long-term ER combined with maintained
      protein intake had a beneficial impact on muscle protein synthesis rate and
      function during ageing.

PMID- 21736768
TI  - Bioavailability of phenols from a phenol-enriched olive oil.
AB  - Phenolic compounds are one of the main reasons behind the healthy properties of
      virgin olive oil (VOO). However, their daily intake from VOO is low compared with
      that obtained from other phenolic sources. Therefore, the intake of VOO enriched
      with its own phenolic compounds could be of interest to increase the daily dose
      of these beneficial compounds. To evaluate the effectiveness of enrichment on
      their bioavailability, the concentration of phenolic compounds and their
      metabolites in human plasma (0, 60, 120, 240 and 300 min) from thirteen healthy
      volunteers (seven men and six women, aged 25 and 69 years) was determined after
      the ingestion of a single dose (30 ml) of either enriched virgin olive oil (EVOO)
      (961.17 mg/kg oil) or control VOO (288.89 mg/kg oil) in a cross-over study.
      Compared with VOO, EVOO increased plasma concentration of the phenol metabolites,
      particularly hydroxytyrosol sulphate and vanillin sulphate (P < 0.05). After the
      consumption of VOO, the maximum concentration of these peaks was reached at 60
      min, while EVOO shifted this maximum to 120 min. Despite these differences, the
      wide variability of results indicates that the absorption and metabolism of olive
      oil phenols are highly dependent on the individual.

PMID- 21736769
TI  - Effect of reduced heifer nutrition during in utero and post-weaning development
      on glucose and acetate kinetics.
AB  - Energetic efficiency was evaluated in composite bred heifers born from dams
      receiving 1.8 or 1.2 kg/d winter supplementation for approximately 80 d before
      parturition. Heifers were then developed post-weaning and randomly assigned to
      heifer development treatments of either control (100 %; ad libitum; n 8/year) or
      restricted (80 %; fed 80 % of supplementation fed to controls adjusted to a
      common body weight: n 8/year) in a 2-year study. A glucose tolerance test (GTT)
      and acetate irreversible loss test (AILT) were administered to heifers at the
      termination of a 140 d development period when the heifers were approximately 403
      d of age and consumed a silage-based diet, and again at 940 d of age when
      pregnant with their second calf and grazing dormant forage. No differences were
      measured (P>0.08) for dam winter nutrition or heifer development treatment for
      baseline serum metabolites or measures in either the GTT or the AILT. However,
      changes in baseline serum concentrations (P>0.05) were different between
      metabolic challenges, which occurred at different stages of development. No
      difference in acetate disappearance (P = 0.18) and half-life (P = 0.66) was
      measured between the two metabolic challenges. A trend for glucose half-life to
      be shorter in heifers born from dams receiving in utero winter treatments that
      supplied 1.2 kg/d of winter supplementation was observed (P = 0.083). Heifers
      developed with lower total DM intake during a 140 d development period had
      similar glucose and acetate incorporation rates as ad libitum-fed heifers when
      evaluated at two different production stages.

PMID- 21736770
TI  - Structure modification of a milk protein-based model food affects postprandial
      intestinal peptide release and fullness in healthy young men.
AB  - Physico-chemical and textural properties of foods in addition to their chemical
      composition modify postprandial metabolism and signals from the gastrointestinal
      tract. Enzymatic cross-linking of protein is a tool to modify food texture and
      structure without changing nutritional composition. We investigated the effects
      of structure modification of a milk protein-based model food and the type of milk
      protein used on postprandial hormonal, metabolic and appetitive responses.
      Healthy males (n 8) consumed an isoenergetic and isovolumic test product
      containing either whey protein (Wh, low-viscous liquid), casein (Cas, high
      viscous liquid) or Cas protein cross-linked with transglutaminase (Cas-TG, rigid
      gel) in a randomised order. Blood samples were drawn for plasma glucose, insulin,
      cholecystokinin (CCK), glucagon-like peptide 1 and peptide YY analysis for 4 h.
      Appetite was assessed at concomitant time points. Cas and Wh were more potent in
      lowering postprandial glucose than Cas-TG during the first hour. Insulin
      concentrations peaked at 30 min, but the peaks were more pronounced for Cas and
      Wh than for Cas-TG. The increase in CCK was similar for Cas and Wh in the first
      15 min, whereas for Cas-TG, the CCK release was significantly lower, but more
      sustained. The feeling of fullness was stronger after the consumption of Cas-TG
      than after the consumption of Cas and Wh. The present results suggest that food
      structure is more effective in modulating the postprandial responses than the
      type of dairy protein used. Modification of protein-based food structure could
      thus offer a possible tool for lowering postprandial glucose and insulin
      concentrations and enhancing postprandial fullness.

PMID- 21736771
TI  - Up-regulation of PPARgamma, heat shock protein-27 and -72 by naringin attenuates
      insulin resistance, beta-cell dysfunction, hepatic steatosis and kidney damage in
      a rat model of type 2 diabetes.
AB  - Naringin, a bioflavonoid isolated from grapefruit, is well known to possess lipid
      lowering and insulin-like properties. Therefore, we assessed whether naringin
      treatment ameliorates insulin resistance (IR), beta-cell dysfunction, hepatic
      steatosis and kidney damage in high-fat diet (HFD)-streptozotocin (STZ)-induced
      type 2 diabetic rats. Wistar albino male rats were fed a HFD (55 % energy from
      fat and 2 % cholesterol) to develop IR and on the 10th day injected with a low
      dose of streptozotocin (40 mg/kg, intraperitoneal (ip)) to induce type 2
      diabetes. After confirmation of hyperglycaemia (>13.89 mmol/l) on the 14th day,
      different doses of naringin (25, 50 and 100 mg/kg per d) and rosiglitazone (5
      mg/kg per d) were administered orally for the next 28 d while being maintained on
      the HFD. Naringin significantly decreased IR, hyperinsulinaemia, hyperglycaemia,
      dyslipidaemia, TNF-alpha, IL-6, C-reactive protein and concomitantly increased
      adiponectin and beta-cell function in a dose-dependent manner. Increased
      thiobarbituric acid-reactive substances and decreased antioxidant enzyme
      activities in the serum and tissues of diabetic rats were also normalised.
      Moreover, naringin robustly increased PPARgamma expression in liver and kidney;
      phosphorylated tyrosine insulin receptor substrate 1 in liver; and stress
      proteins heat shock protein (HSP)-27 and HSP-72 in pancreas, liver and kidney. In
      contrast, NF-kappaB expression in these tissues along with sterol regulatory
      element binding protein-1c and liver X receptor- expressions in liver were
      significantly diminished. In addition, microscopic observations validated that
      naringin effectively rescues beta-cells, hepatocytes and kidney from HFD-STZ
      mediated oxidative damage and pathological alterations. Thus, this seminal study
      provides cogent evidence that naringin ameliorates IR, dyslipidaemia, beta-cell
      dysfunction, hepatic steatosis and kidney damage in type 2 diabetic rats by
      partly regulating oxidative stress, inflammation and dysregulated adipocytokines
      production through up-regulation of PPARgamma, HSP-27 and HSP-72.

PMID- 21736772
TI  - Probiotic and prebiotic claims in Europe: seeking a clear roadmap.

PMID- 21736773
TI  - Bone-protective effects of bioactive fractions and ingredients in Sambucus
      williamsii HANCE.
AB  - Our previous study demonstrated that 60 % ethanol crude extract of Sambucus
      williamsii HANCE (SWH) improved bone mass, bone strength and bone micro-structure
      in both ovariectomised (OVX) rats and mice. The present study aims to identify
      the bioactive fractions and ingredients in SWH that account for its
      osteoprotective effects. Bilateral sham-operated mice acted as controls. OVX
      C57BL/6J mice, aged 12 weeks, were orally administrated daily with vehicle or
      17beta-oestradiol (3.2 mg/kg), SWH (60 % ethanol crude extract; 1.0 g/kg), SWA
      (water eluate; 0.570 g/kg), SWB (30 % ethanol eluate; 0.128 g/kg) or SWC (50 and
      95 % ethanol eluates; 0.189 g/kg) for 12 weeks. The effects of the different
      fractions on bone properties in the OVX mice model were studied. In addition,
      their effects on osteoblast proliferation and differentiation were evaluated in
      UMR 106 cells. SWC significantly restored bone mineral density and improved bone
      size and bone content parameters in the femur and tibia as well as increased
      biomechanical strength at the tibia diaphysis in OVX mice. Similarly, SWC was the
      most potent fraction in stimulating cell proliferation and differentiation in UMR
      106 cells. Also, SWC did not alter uterus weight in OVX mice. Nine major peaks,
      seven lignans and two phenolic acids, in the HPLC fingerprint of the SWC fraction
      were identified, isolated and characterised. In conclusion, the present study
      demonstrated that SWC was the most potent fraction in SWH that exerted anti
      osteoporotic effects. Furthermore, lignans might be the potential bioactive
      components in SWC.

PMID- 21736774
TI  - Tannic acid is more effective than clofibrate for the elevation of hepatic beta
      oxidation and the inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase and
      aortic lesion formation in apo E-deficient mice.
AB  - The effects of tannic acid (TA) supplementation (0.02 %, wt/wt) were compared
      with the effects of clofibrate (CF) supplementation (0.02 %, wt/wt) in apo E
      deficient (apo E(- / -)) mice fed a AIN-76 semi-synthetic diet (normal diet) over
      20 weeks. The mice were monitored for the modulation of hepatic mRNA expression
      and the activities of lipid-regulating enzymes. Both TA and CF supplementation
      lowered hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) activity and
      prevented atherosclerotic lesion formation in comparison with the control group.
      Hepatic carnitine palmitoyl transferase and beta-oxidation activities were
      significantly higher in the TA and CF groups than in the control group. Both CF
      and TA supplementation resulted in significant decreases in hepatic HMGR mRNA
      levels in association with its enzyme activity. However, in contrast to CF
      supplementation, TA supplementation seemed to decrease the accumulation of
      hepatic lipids in the apo E(- / -) mice without increasing liver weight. These
      results suggest that the overall effect of TA is more desirable than CF for the
      alleviation of hepatic lipogenesis and atherogenesis in apo E(- / -) mice.

PMID- 21736775
TI  - Effects of dietary protein content and 2-hydroxy-4-methylthiobutanoic acid or DL
      methionine supplementation on performance and oxidative status of broiler
      chickens.
AB  - Besides its typical role as an amino acid in protein synthesis, methionine is an
      important intermediate in methylation reactions. In addition, it can also be
      converted to cysteine and hence plays a role in the defence against oxidative
      stress. The present study was conducted to investigate further the role of DL
      methionine (DLM) and its hydroxy analogue, DL-2-hydroxy-4-methylthiobutanoic acid
      (DL-HMTBA), on zootechnical performance and oxidative status of broiler chickens.
      Male broiler chickens were reared on two diets differing in crude protein (CP)
      content (low-protein, 18.3 % v. high-protein, 23.2 % CP) and were supplemented
      either with 0.25 % DLM or 0.25 % DL-HMTBA. Reducing the dietary protein content
      resulted in an impaired body weight gain (P < 0.0001). However, supplementation
      of DL-HMTBA to the low-protein diet partially alleviated these negative effects
      (P = 0.0003). This latter phenomenon could be explained by the fact that chickens
      fed DL-HMTBA-supplemented diets displayed a better antioxidant status as
      reflected in lower lipid peroxidation probably as a consequence of their higher
      hepatic concentrations of total and reduced glutathione compared with their DLM
      counterparts. On the other hand, within the high protein levels, uric acid might
      be an important antioxidant to explain the lower lipid peroxidation of high
      protein DL-HMTBA-supplemented chickens. Hepatic methionine sulfoxide reductase-A
      gene expression was not significantly affected by the dietary treatments. In
      conclusion, the present study indicates that there are interactions between
      dietary protein content and supplementation of methionine analogues with respect
      to broiler performance and antioxidant status, also suggesting a causal link
      between these traits.

PMID- 21736776
TI  - Vitamin A deficiency in patients with hepatitis C virus-related chronic liver
      disease.
AB  - Hepatitis C virus (HCV) infection is associated with oxidative stress and vitamin
      A possesses antioxidant activity. The objective of the present study was to
      investigate vitamin A nutritional status in chronic hepatitis, liver cirrhosis
      and hepatocellular carcinoma (HCC), according to biochemical, functional and
      dietetic indicators correlating these findings with liver function, liver damage
      and death. Vitamin A nutritional status was analysed by serum retinol levels,
      dietetic indicators and functional indicators. A total of 140 patients with HCV
      related liver disease were enrolled. Vitamin A deficiency was detected in 54.3 %
      of all patients, and there was a progressive drop in serum retinol levels from
      chronic hepatitis C patients towards cirrhosis and HCC patients. Increased total
      bilirubin, liver transaminases and prothrombin time, presence of hepatic
      encephalopathy and ascites were related to reduced serum retinol levels, and
      values <= 0.78 MUmol/l of serum retinol were associated with liver-related death.
      A high prevalence of inadequate intake of vitamin A was observed in all stages of
      chronic liver disease. The functional indicator was not an adequate parameter for
      evaluating the vitamin A nutritional status. Therefore, serum retinol
      concentration is related to severity of the disease, liver complications and
      mortality. The effectiveness of nutritional counselling and measures of
      intervention in this group in improving vitamin A nutritional status should be
      examined further in a controlled study.

PMID- 21736777
TI  - Glycaemic index and glycaemic load of breakfast predict cognitive function and
      mood in school children: a randomised controlled trial.
AB  - The macronutrient composition of a breakfast that could facilitate performance
      after an overnight fast remains unclear. As glucose is the brain's major energy
      source, the interest is in investigating meals differing in their blood glucose
      raising potential. Findings vary due to unaccounted differences in
      glucoregulation, arousal and cortisol secretion. We investigated the effects of
      meals differing in glycaemic index (GI) and glycaemic load (GL) on cognition and
      mood in school children. A total of seventy-four school children were matched and
      randomly allocated either to the high-GL or low-GL group. Within each GL group,
      children received high-GI and low-GI breakfasts. Cognitive function (CF) and mood
      were measured 95-140 min after breakfast. Blood glucose and salivary cortisol
      were measured at baseline, before and after the CF tests. Repeated-measures ANOVA
      was used to identify differences in CF, mood, glucose and cortisol levels between
      the breakfasts. Low-GI meals predicted feeling more alert and happy, and less
      nervous and thirsty (P < 0.05 for each); high-GL meals predicted feeling more
      confident, and less sluggish, hungry and thirsty (P < 0.05 for each). High-GL (P
      < 0.001) and high-GI (P = 0.05) meals increased glucose levels 90 min after
      breakfast, and high-GI meals increased cortisol levels (P < 0.01). When baseline
      mood, glucose and cortisol levels were considered, low-GI meals predicted better
      declarative-verbal memory (P = 0.03), and high-GI meals better vigilance (P <
      0.03); observed GI effects were valid across GL groups. GI effects on cognition
      appear to be domain specific. On balance, it would appear that the low-GI high-GL
      breakfast may help to improve learning, and of potential value in informing
      government education policies relating to dietary recommendations and
      implementation concerning breakfast.

PMID- 21736778
TI  - Positive outcomes of oil palm phenolics on degenerative diseases in animal
      models.
AB  - It is well established that plant phenolics elicit various biological activities,
      with positive effects on health. Palm oil production results in large volumes of
      aqueous by-products containing phenolics. In the present study, we describe the
      effects of oil palm phenolics (OPP) on several degenerative conditions using
      various animal models. OPP reduced blood pressure in a NO-deficient rat model,
      protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque
      formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model
      of the metabolic syndrome and type 2 diabetes, OPP protected against multiple
      aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP
      protected against cancer progression. Microarray studies on the tumours showed
      differential transcriptome profiles that suggest anti-tumour molecular mechanisms
      involved in OPP action. Thus, initial studies suggest that OPP may have potential
      against several chronic disease outcomes in mammals.

PMID- 21736779
TI  - Supplement of bamboo extract lowers serum monocyte chemoattractant protein-1
      concentration in mice fed a diet containing a high level of saturated fat.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory chemokine up
      regulated in obese subjects, contributing to the development of type 2 diabetes.
      The present study investigated the inhibitory effect of an ethanol-water extract
      from bamboo (BEX, Phyllostachys edulis) on the blood concentration of MCP-1.
      C57BL/6J mice were fed a standard diet or a high-fat diet with or without the BEX
      supplement (11 g dry mass/17 000 kJ) for 6 months. A total of ten mice were used
      in each group. Body weight and food consumption were measured weekly. After
      euthanisation, the weight of visceral fat and circulating MCP-1 concentration
      were measured. In comparison with the standard control group, the high-fat
      control group had increased body weight, abdominal fat storage and serum MCP-1
      concentration by 60 % (P < 0.001), 266 % (P < 0.001) and 180 % (P < 0.01),
      respectively. In comparison with the high-fat control group, the high-fat BEX
      group showed a 3 % decrease in body weight (P < 0.01), 24 % decrease in
      mesenteric fat depot (P < 0.01) and 49 % decrease in serum MCP-1 concentration (P
      < 0.05). The present study suggests that the BEX supplement in the high-fat diet
      ameliorates elevated MCP-1 concentrations in the blood, and whether this is
      related to modulated endocrine properties of the visceral fat is to be studied.

PMID- 21736780
TI  - Antioxidant micronutrient supplementation increases erythrocyte membrane fluidity
      in adults from a rural Chinese community.
AB  - The objective of the present study was to investigate age-related differences in
      erythrocyte membrane fluidity (EMF) and changes in antioxidant capacity following
      supplementation. A total of seventy-four children were randomly divided into two
      groups: group A1 was the placebo-controlled group and group A2 was supplemented
      daily with 600 MUg retinol, 1.0 mg beta-carotene, 100 mg tocopherol, 300 mg
      ascorbic acid and 200 MUg Se. A total of ninety young people were randomly
      divided into B1 and B2 groups, and ninety-one elderly subjects were divided into
      C1 and C2 groups. Groups B1 and C1 were placebo-controlled groups, and groups B2
      and C2 were daily supplemented with 900 MUg retinol, 1.5 mg beta-carotene, 200 mg
      tocopherol, 500 mg ascorbic acid and 400 MUg Se. Results showed that plasma
      malondialdehyde (MDA) was 5.35 MUmol/l in children, which was lower than in young
      and elderly people. The MDA levels of the young and elderly individuals in the
      treated groups were significantly lower compared with the control groups, but the
      supplementation did not alter MDA levels in children. At baseline, there was a
      lower value of polarisation (rho) and microviscosity (eta) in children,
      indicating a higher EMF, than in both the young and elderly subjects. After the 2
      month trial, the rho and eta values of young and elderly subjects in the treated
      groups decreased significantly in comparison with the placebo groups, indicating
      an increase in EMF. In conclusion, there was a background of higher MDA levels
      and lower EMF in young and elderly people than in children, which could be
      improved by antioxidant supplementation.

PMID- 21736781
TI  - National Diet and Nutrition Survey: UK food consumption and nutrient intakes from
      the first year of the rolling programme and comparisons with previous surveys.
AB  - The National Diet and Nutrition Survey (NDNS) is a cross-sectional survey
      designed to gather data representative of the UK population on food consumption,
      nutrient intakes and nutritional status. The objectives of the present paper were
      to identify and describe food consumption and nutrient intakes in the UK from the
      first year of the NDNS rolling programme (2008-09) and compare these with the
      2000-01 NDNS of adults aged 19-64 years and the 1997 NDNS of young people aged 4
      18 years. Differences in median daily food consumption and nutrient intakes
      between the surveys were compared by sex and age group (4-10 years, 11-18 years
      and 19-64 years). There were no changes in energy, total fat or carbohydrate
      intakes between the surveys. Children aged 4-10 years had significantly lower
      consumption of soft drinks (not low calorie), crisps and savoury snacks and
      chocolate confectionery in 2008-09 than in 1997 (all P < 0.0001). The percentage
      contribution of non-milk extrinsic sugars to food energy was also significantly
      lower than in 1997 in children aged 4-10 years (P < 0.0001), contributing 13.7
      14.6 % in 2008-09 compared with 16.8 % in 1997. These changes were not as marked
      in older children and there were no changes in these foods and nutrients in
      adults. There was still a substantial proportion (46 %) of girls aged 11-18 years
      and women aged 19-64 years (21 %) with mean daily Fe intakes below the lower
      reference nutrient intake. Since previous surveys there have been some positive
      changes in intakes especially in younger children. However, further attention is
      required in other groups, in particular adolescent girls.

PMID- 21736782
TI  - Effect of the fat composition of a single high-fat meal on inflammatory markers
      in healthy young women.
AB  - The aim of the present study was to examine the effect of a single high-fat meal
      with different fat quality on circulating inflammatory markers and gene
      expression in peripheral blood mononuclear cells (PBMC) to elucidate the role of
      fat quality on postprandial inflammation. A postprandial study with fourteen
      healthy females consuming three test meals with different fat quality was
      performed. Test days were separated by 2 weeks. Fasting and postprandial blood
      samples at 3 and 6 h after intake were analysed. The test meal consisted of three
      cakes enriched with coconut fat (43 % energy as saturated fat and 1 % energy as
      alpha-linolenic acid (ALA)), linseed oil (14 % energy as ALA and 30 % energy as
      saturated fat) and cod liver oil (5 % energy as EPA and DHA and 5 % energy as ALA
      in addition to 31 % energy as saturated fat). In addition, ex vivo PBMC
      experiments were performed in eight healthy subjects investigating the effects of
      EPA and ALA on release and gene expression of inflammatory markers. The IL-8 mRNA
      level was significantly increased after intake of the cod liver oil cake at 6 h
      compared with fasting level, which was significantly different from the effect
      observed after the intake of linseed cake. In contrast, no effect was seen on
      circulating level of IL-8. In addition, ALA and EPA were shown to elicit
      different effects on the release and mRNA expression levels of inflammatory
      markers in PBMC cultured ex vivo, with EPA having the most prominent pro
      inflammatory potential.

PMID- 21736783
TI  - The difference between a prophet and a madman.

PMID- 21736784
TI  - Fish intake, erythrocyte n-3 fatty acid status and metabolic health in Danish
      adolescent girls and boys.
AB  - Marine n-3 long-chain PUFA (n-3 LCPUFA) may have a beneficial effect on several
      aspects of the metabolic syndrome (dyslipidaemia, insulin resistance,
      hypertension and abdominal obesity). The metabolic syndrome is increasing in
      prevalence during adolescence, but only few studies have investigated the effects
      of n-3 LCPUFA in adolescence. The present study examines associations between
      fish intake (assessed by a 7 d pre-coded food diary), erythrocyte (RBC) DHA
      status (analysed by GC) and metabolic syndrome measures (anthropometry, blood
      pressure and plasma lipids, insulin and glucose) in 109 17-year-old children from
      the Copenhagen Birth Cohort Study. Of the children, 8 % were overweight or obese
      and few showed signs of the metabolic syndrome, but all the metabolic syndrome
      variables were correlated. Median fish intake was 10.7 (interquartile range 3.6
      21.2) g/d. Boys tended to have a higher fish intake (P = 0.052), but girls had
      significantly higher RBC levels of DHA (P = 0.001). Sex and fish intake explained
      37 % of the variance in RBC-DHA (P < 0.001). After adjusting for confounders,
      high DHA status was found to be significantly correlated with higher systolic
      blood pressure (P = 0.014) and increased fasting insulin (P = 0.018), but no
      adverse association was observed with the mean metabolic syndrome z-score.
      Overall, the present study showed the expected association between fish intake
      and RBC-DHA, which in contrast to our expectations tended to be associated with a
      poorer metabolic profile. Whether these results reflect the physiological
      function of n-3 LCPUFA, lifestyle factors associated with fish intake in Denmark,
      or mere chance remains to be investigated.

PMID- 21736785
TI  - Health effects of green tea catechins in overweight and obese men: a randomised
      controlled cross-over trial.
AB  - Regular consumption of green tea may be cardioprotective. In the present study we
      investigated the health effects of dietary supplementation with green tea
      catechins and the potential modifying effect of the catechol-O-methyltransferase
      (COMT) Val/Met genotype. Subjects (sedentary males, aged 40-69 years, with BMI >=
      28 and <= 38 kg/m(2)) were randomly assigned to consume decaffeinated green tea
      extract (DGT; 530 mg containing about 400 mg total catechins/capsule, twice
      daily) and placebo in a complete cross-over design. Ambulatory blood pressure and
      biomarkers of metabolic function (cholesterol, TAG, glucose and insulin) were
      measured at weeks 0 and 6. Although a marked increase in the concentration of
      plasma epigallocatechin gallate (EGCG), urinary epigallocatechin (EGC) and
      urinary 4'-O-methyl EGC was found after DGT treatment, no effect on blood
      pressure or biomarkers of metabolic function was observed. However, a period *
      treatment interaction (P < 0.05) was detected for body-weight change. Despite a
      similar increase in estimated energy intake during intervention period 1, body
      weight decreased by 0.64 (sd 2.2) kg and increased by 0.53 (sd 1.9) kg in the DGT
      and placebo groups, respectively (P = 0.025), suggesting a protective effect of
      green tea catechins on weight gain. Additionally, the COMT Val/Met genotype
      influenced urinary accumulation of EGC and 4'-O-methyl EGC (P < 0.01). Mean
      concentrations were lower in individuals homozygous for the high-activity G
      allele, possibly reflecting increased metabolic flux and a more rapid conversion
      to downstream metabolic species, compared with individuals carrying at least one
      copy of the low-activity A-allele. Additional studies are needed to confirm these
      findings and further explore the modifying effect of genotype.

PMID- 21736786
TI  - Mild dehydration impairs cognitive performance and mood of men.
AB  - The present study assessed the effects of mild dehydration on cognitive
      performance and mood of young males. A total of twenty-six men (age 20.0 (sd 0.3)
      years) participated in three randomised, single-blind, repeated-measures trials:
      exercise-induced dehydration plus a diuretic (DD; 40 mg furosemide); exercise
      induced dehydration plus placebo containing no diuretic (DN); exercise while
      maintaining euhydration plus placebo (EU; control condition). Each trial included
      three 40 min treadmill walks at 5.6 km/h, 5 % grade in a 27.7 degrees C
      environment. A comprehensive computerised six-task cognitive test battery, the
      profile of mood states questionnaire and the symptom questionnaire (headache,
      concentration and task difficulty) were administered during each trial. Paired t
      tests compared the DD and DN trials resulting in >1 % body mass loss (mean 1.59
      (sd 0.42) %) with the volunteer's EU trial (0.01 (sd 0.03) %). Dehydration
      degraded specific aspects of cognitive performance: errors increased on visual
      vigilance (P = 0.048) and visual working memory response latency slowed (P =
      0.021). Fatigue and tension/anxiety increased due to dehydration at rest (P =
      0.040 and 0.029) and fatigue during exercise (P = 0.026). Plasma osmolality
      increased due to dehydration (P < 0.001) but resting gastrointestinal temperature
      was not altered (P = 0.238). In conclusion, mild dehydration without hyperthermia
      in men induced adverse changes in vigilance and working memory, and increased
      tension/anxiety and fatigue.

PMID- 21736787
TI  - A dairy product fermented by lactobacilli cancels the adverse effects of
      hypochlorhydria induced by a proton pump inhibitor on bone metabolism in growing
      rats.
AB  - The purpose of the present study is to investigate the effects of hypochlorhydria
      induced by proton pump inhibitor (PPI) administration and intake of a dairy
      product fermented by lactobacilli (DFL) on bone metabolism in growing rats. Male
      rats, aged 3 weeks, were divided into two groups: a control group fed a casein
      based diet and a group fed a DFL-based diet. Each group was fed its respective
      experimental diets for 9 d. At day 5 of the feeding period, each group was
      divided into two subgroups: one that received a saline injection and one that
      received a PPI injection. Rats were subcutaneously administered saline or PPI for
      5 d. Faecal Ca excretion was determined from day 6 to day 9. At the end of the
      experiment, plasma and femurs were collected. Administration of PPI significantly
      decreased bone mineral density (shown by X-ray computerised tomography) and bone
      strength (shown by a three-point bending test) in the control group. Plasma
      osteocalcin, type I collagen C-telopeptides, 1,25-dihydroxyvitamin D and
      parathyroid hormone concentrations were elevated by PPI administration in the
      control group. Faecal Ca excretion and urinary P excretion in the control group
      were remarkably increased by PPI administration. On the other hand, these adverse
      effects of PPI were not observed in the DFL group. These results suggest that
      hypochlorhydria-induced bone loss may result from high bone turnover induced by
      secondary hyperparathyroidism due to Ca malabsorption and that DFL intake cancels
      these adverse effects probably via improving Ca malabsorption in growing rats.

PMID- 21736788
TI  - A high dietary concentration of inulin is necessary to reduce the incidence of
      swine dysentery in pigs experimentally challenged with Brachyspira
      hyodysenteriae.
AB  - A total of sixty surgically castrated male pigs (Large White * Landrace) weighing
      31.2 (sd 4.3) kg were used in a randomised block experiment to examine the effect
      of added dietary inulin (0, 20, 40 and 80 g/kg) on the occurrence of swine
      dysentery (SD) and on fermentation characteristics in the large intestine after
      experimental challenge with the causative spirochaete Brachyspira hyodysenteriae.
      The pigs were allowed to adapt to the diets for 2 weeks before each pig was
      challenged orally four times with a broth culture containing B. hyodysenteriae on
      consecutive days. Increasing dietary levels of inulin linearly (P = 0.001)
      reduced the risk of pigs developing SD; however, eight out of fifteen pigs fed
      the diet with 80 g/kg inulin still developed the disease. The pH values in the
      caecum (P = 0.072) tended to decrease, and in the upper colon, the pH values did
      decrease (P = 0.047) linearly with increasing inulin levels in the diets, most
      probably due to a linear increase in the concentration of total volatile fatty
      acids in the caecum (P = 0.018), upper colon (P = 0.001) and lower colon (P =
      0.013). In addition, there was a linear reduction in the proportion of the
      branched-chain fatty acids isobutyric acid and isovaleric acid in the caecum (P =
      0.015 and 0.026) and upper colon (P = 0.011 and 0.013) with increasing levels of
      dietary inulin. In conclusion, the present study showed that a diet supplemented
      with a high level of inulin (80 g/kg) but not lower levels reduced the risk of
      pigs developing SD, possibly acting through a modification of the microbial
      fermentation patterns in the large intestine.

PMID- 21736789
TI  - A variant near the melanocortin-4 receptor gene regulates postprandial lipid
      metabolism in a healthy Caucasian population.
AB  - The melanocortin-4 receptor (MC4R) is an essential regulator of food intake and
      energy homeostasis. Previous data suggest an influence of MC4R activity on TAG
      levels. Thus, the aim of the present study was to determine whether the presence
      of the rs12970134 polymorphism near the MC4R gene could influence postprandial
      lipoprotein metabolism in healthy subjects. A total of eighty-eight volunteers
      were selected, fifty-three homozygous for the common genotype (G/G) and thirty
      five carriers for the minor A-allele (G/A and A/A). They were given a fat-rich
      meal containing 1 g fat and 7 mg cholesterol/kg body weight and vitamin A (60,000
      IU/m(2) body surface). Fat accounted for 60 % of energy, and protein and
      carbohydrates accounted for 15 and 25 % of energy, respectively. Blood samples
      were taken at time 0, every 1 h until 6 h and every 2.5 h until 11 h. Total
      cholesterol and TAG in plasma, and cholesterol, TAG and retinyl palmitate in TAG
      rich lipoproteins (TRL, large and small TRL) were separated by
      ultracentrifugation. Individuals carrying the G/G genotype displayed a higher
      postprandial response of plasma TAG (P = 0.033), total cholesterol (P = 0.019)
      and large TRL-TAG (P = 0.023) than did carriers of the minor A-allele.
      Furthermore, G/G subjects showed a greater postprandial response of small TRL
      apoB48 than did carriers of the A-allele (P = 0.032). These results suggest that
      the rs12970134 polymorphism near the MC4R gene region may partly explain the
      inter-individual differences in postprandial lipoprotein response in healthy
      subjects.

PMID- 21736790
TI  - Length and site of the small intestine exposed to fat influences hunger and food
      intake.
AB  - The site of intestinal fat delivery affects satiety and may affect food intake in
      humans. Animal data suggest that the length of the small intestine exposed to fat
      is also relevant. The aim of the present study was to investigate whether
      increasing the areas of intestinal fat exposure and the way it is exposed would
      affect satiety parameters and food intake. In the present single-blind,
      randomised, cross-over study, fifteen volunteers, each intubated with a naso
      ileal tube, received four treatments on consecutive days. The oral control
      (control treatment) was a liquid meal (LM) containing 6 g fat ingested at t = 0
      min, with saline infusion at t = 30-120 min. Experimental treatments were a fat
      free LM at t = 0 min, with either 6 g oil delivered sequentially (2 g duodenal, t
      = 30-60 min; 2 g jejunal, t = 60-90 min; 2 g ileal, t = 90-120 min),
      simultaneously (2 g each to all sites, t = 30-120 min) or ileal only (6 g ileal,
      t = 30-120 min). Satiety parameters (hunger and fullness) and cholecystokinin
      (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) secretion were measured
      until t = 180 min, when ad libitum food intake was assessed. Only the ileum
      treatment reduced food intake significantly over the control treatment. The ileum
      and simultaneous treatments significantly reduced hunger compared with the
      control treatment. Compared with control, no differences were observed for PYY,
      CCK and GLP-1 with regard to 180 min integrated secretion. Ileal fat infusion had
      the most pronounced effect on food intake and satiety. Increasing the areas of
      intestinal fat exposure only affected hunger when fat was delivered
      simultaneously, not sequentially, to the exposed areas. These results demonstrate
      that ileal brake activation offers an interesting target for the regulation of
      ingestive behaviour.

PMID- 21736791
TI  - Vitamin D status has a linear association with seasonal infections and lung
      function in British adults.
AB  - Higher vitamin D concentrations have been proposed as a protective 'seasonal
      stimulus' against influenza, and there are suggestions for associations with
      other aspects of respiratory health. The aim of the present study was to
      investigate the relationship of current vitamin D status (measured by 25
      hydroxyvitamin D, 25(OH)D) with respiratory infections and lung function. We used
      cross-sectional data from 6789 participants in the nationwide 1958 British birth
      cohort who had measurements of 25(OH)D, lung function (forced expiratory volume
      in 1 s (FEV1) and forced vital capacity (FVC)) and respiratory infections
      available from the age of 45 years. In this population, the prevalence of
      respiratory infections had a strong seasonal pattern in the opposite direction to
      the pattern for 25(OH)D concentrations. Each 10 nmol/l increase in 25(OH)D was
      associated with a 7 % lower risk of infection (95 % CI 3, 11 %) after adjustment
      for adiposity, lifestyle and socio-economic factors. For FEV1 and FVC, each 10
      nmol/l increase in 25(OH)D was associated with 8 (95 % CI 3, 13) ml and 13 (95 %
      CI 7, 20) ml higher volume, respectively, after controlling for covariates.
      Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after
      further adjustment for infection and other respiratory illness. In conclusion,
      vitamin D status had a linear relationship with respiratory infections and lung
      function. Randomised controlled trials are warranted to investigate the role of
      vitamin D supplementation on respiratory health and to establish the underlying
      mechanisms.

PMID- 21736792
TI  - Oil palm vegetation liquor: a new source of phenolic bioactives.
AB  - Waste from agricultural products represents a disposal liability, which needs to
      be addressed. Palm oil is the most widely traded edible oil globally, and its
      production generates 85 million tons of aqueous by-products annually. This
      aqueous stream is rich in phenolic antioxidants, which were investigated for
      their composition and potential in vitro biological activity. We have identified
      three isomers of caffeoylshikimic acid as major components of oil palm phenolics
      (OPP). The 2,2-diphenyl-1-picrylhydrazyl assay confirmed potent free radical
      scavenging activity. To test for possible cardioprotective effects of OPP, we
      carried out in vitro LDL oxidation studies as well as ex vivo aortic ring and
      mesenteric vascular bed relaxation measurements. We found that OPP inhibited the
      Cu-mediated oxidation of human LDL. OPP also promoted vascular relaxation in both
      isolated aortic rings and perfused mesenteric vascular beds pre-contracted with
      noradrenaline. To rule out developmental toxicity, we performed teratological
      studies on rats up to the third generation and did not find any congenital
      anomalies. Thus, these initial studies suggest that OPP is safe and may have a
      protective role against free radical damage, LDL oxidation and its attendant
      negative effects, as well as vascular constriction in mitigating atherosclerosis.
      Oil palm vegetation liquor thus represents a new source of phenolic bioactives.

PMID- 21736793
TI  - Fish oil combined with SCFA synergistically prevent tissue accumulation of NEFA
      during weight loss in obese mice.
AB  - Based on their proposed metabolic effects, we examined whether fish oil (FO) and
      SCFA, alone or in combination, accelerate weight loss and the resultant metabolic
      improvements. Obesity was induced in male C57BL/6J mice by high-energy feeding
      for 10 weeks. The mice were transferred to a low-fat diet (2.5w%) for 4 weeks,
      the source of fat being either FO, a lard-safflower oil mix (control), or both
      types combined with SCFA. Weight, fasting insulin, tissue and serum lipid
      concentrations, as well as mRNA amount of genes related to adipose inflammation
      and hepatic fat oxidation were determined. All groups lost weight and showed
      reduced fasting insulin concentrations and reduced liver TAG. However, weight
      loss on the control-fat diet caused significant increase in hepatic and cardiac
      NEFA. Substituting 20 % of the fat with SCFA increased weight loss by 48 % and
      reduced fasting insulin 1.5-fold more than the no-SCFA diets. It furthermore
      significantly increased the amount of mRNA for PPAR-alpha, and decreased the mRNA
      amount for NF-kappaB in the liver and white adipose tissue. The FO diets enhanced
      improvement of tissue lipid levels. Thus, FO improved liver TAG and NEFA levels
      compared with weight loss on the control diet. Combining FO and SCFA further
      reduced tissue NEFA accumulation. In conclusion, we found that dietary SCFA had a
      significant impact on gene expression in the liver and adipose tissue, and that
      the effect of FO on tissue NEFA content was modified by SCFA. Thus, interactions
      between fatty acids should be considered when studying the effects of specific
      fatty acids.

PMID- 21736794
TI  - Long-term dietary antioxidant cocktail supplementation effectively reduces renal
      inflammation in diabetic mice.
AB  - Diabetic nephropathy is a serious complication for diabetic patients, yet the
      precise mechanism that underlies the development of diabetic complications
      remains unknown. We hypothesised that dietary antioxidant supplementation with
      single N-acetylcysteine (NAC) or vitamin C combined with either vitamin E or
      vitamin E and NAC improves diabetic renal inflammation through the modulation of
      blood glucose levels, oxidative stress and inflammatory response. Experimental
      animals were treated with alloxan monohydrate to induce diabetes. Mice were
      divided into five groups and supplemented with single or a combination of
      antioxidants. Body weights and blood glucose levels were measured once a week.
      After 8 weeks of dietary antioxidant supplementation, mice were killed and blood
      urea N (BUN) and plasma creatinine levels were measured to evaluate renal
      function. NF-kappaB protein was indirectly demonstrated by the phosphorylated
      IkappaBalpha (pIkappaBalpha) level, and the expressions of oxidative stress- and
      inflammatory response-related proteins were also determined. We demonstrated that
      dietary antioxidant supplementation decreased lipid peroxidation levels
      demonstrated by thiobarbituric acid-reacting substances, BUN and plasma
      creatinine levels in diabetic kidneys. Moreover, dietary antioxidant cocktail
      supplementation improved blood glucose levels and selectively regulated the
      expressions of Cu-Zn superoxide dismutase, haeme oxygenase-1, pIkappaBalpha,
      inducible NO synthase, cyclo-oxygenase-2 and C-reactive protein in diabetic
      kidneys effectively. These findings demonstrated that diabetic renal failure was
      associated with inflammatory responses induced by hyperglycaemia. In addition,
      results in the study suggest that antioxidant cocktail supplementation may have
      beneficial effects on diabetic nephropathy through selective reduction of blood
      glucose levels and inflammatory response.

PMID- 21736795
TI  - Diet * genotype interactions in hepatic cholesterol and lipoprotein metabolism in
      Atlantic salmon (Salmo salar) in response to replacement of dietary fish oil with
      vegetable oil.
AB  - The present study investigates the effects of genotype on responses to
      alternative feeds in Atlantic salmon. Microarray analysis of the liver
      transcriptome of two family groups, lean or fat, fed a diet containing either a
      fish oil (FO) or a vegetable oil (VO) blend indicated that pathways of
      cholesterol and lipoprotein metabolism might be differentially affected by the
      diet depending on the genetic background of the fish, and this was further
      investigated by real-time quantitative PCR, plasma and lipoprotein biochemical
      analysis. Results indicate a reduction in VLDL and LDL levels, with no changes in
      HDL, when FO is replaced by VO in the lean family group, whereas in fat fish fed
      FO, levels of apoB-containing lipoproteins were low and comparable with those fed
      VO in both family groups. Significantly lower levels of plasma TAG and LDL-TAG
      were measured in the fat group that was independent of diet, whereas plasma
      cholesterol was significantly higher in fish fed the FO diet in both groups.
      Hepatic expression of genes involved in cholesterol homeostasis, beta-oxidation
      and lipoprotein metabolism showed relatively subtle changes. A significantly
      lower expression of genes considered anti-atherogenic in mammals (ATP-binding
      cassette transporter A1, apoAI, scavenger receptor class B type 1, lipoprotein
      lipase (LPL)b (TC67836) and LPLc (TC84899)) was found in lean fish, compared with
      fat fish, when fed VO. Furthermore, the lean family group appeared to show a
      greater response to diet composition in the cholesterol biosynthesis pathway,
      mediated by sterol-responsive element-binding protein 2. Finally, the presence of
      three different transcripts for LPL, with differential patterns of nutritional
      regulation, was demonstrated.

PMID- 21736796
TI  - Effects of Nori- and Wakame-enriched meats with or without supplementary
      cholesterol on arylesterase activity, lipaemia and lipoproteinaemia in growing
      Wistar rats.
AB  - Some seaweeds exert antioxidant and hypocholesterolaemic properties. The effects
      of diets including restructured meats (RM) containing Wakame (W) or Nori (N)
      algae on arylesterase (AE) activity and lipoprotein concentration and composition
      were tested. In the present study, six groups of ten male growing Wistar rats
      each were fed a mix of 85 % AIN-93M diet and 15 % freeze-dried RM for 35 d. The
      control group (C) consumed control RM, the W and N groups consumed RM with 5 % W
      and 5 % N, respectively. The cholesterol-enriched C (CC), W (CW) and N (CN)
      groups consumed their corresponding basal diets with supplementary cholesterol
      (2.43 %) and cholic acid (0.49 %). Cholesterol in the diet induced lower (P <
      0.001) growth ratios. Both W and N diets significantly increased AE activity.
      VLDL-cholesterol values were lower in N rats than in W rats. AE activity
      increased (P < 0.001) in CC and CW rats but not in CN rats compared with their
      corresponding counterparts. AE was lower (P < 0.05) in the CN group than in the
      CC and CW groups. The CN diet partially blocked (P < 0.001) the
      hypercholesterolaemic induction observed in CC and CW diets and reduced TAG
      levels (at least P < 0.05) with respect to those of CC rats. Although dietary
      cholesterol supplementation increased total cholesterol, VLDL-cholesterol and
      (intermediate-density lipoprotein+LDL)-cholesterol (all P < 0.001) in all rats,
      the CN diet moderately improved the lipoprotein profile of hypercholesterolaemic
      rats. Changes in AE activity and plasma cholesterol in CN rats but not in CW rats
      suggest a possible relationship between the two parameters. It is concluded that
      inclusion of RM enriched with N may be used in hypercholesterolaemic diets to
      improve lipoprotein metabolism.

PMID- 21736797
TI  - Dietary fructo-oligosaccharides improve insulin sensitivity along with the
      suppression of adipocytokine secretion from mesenteric fat cells in rats.
AB  - Short-chain fructo-oligosaccharides (FOS) are known to have beneficial effects on
      health. However, the effects of FOS on insulin resistance have not been fully
      clarified. We observed the effects of FOS feeding on insulin sensitivity and
      adipocytokine release from abdominal adipocytes in weaning rats. Male Sprague
      Dawley rats, 3 weeks old, were divided into three groups and fed a sucrose-based
      American Institute of Nutrition (AIN)-93 growth diet (control), the control diet
      containing 5 % FOS for 5 weeks (FOS-5wk) or the control diet for 2 weeks followed
      by the 5 % FOS diet for 3 weeks (FOS-3wk). Tail blood was collected after fasting
      for 9 h on day 33 of feeding, and glucose and insulin levels were measured. On
      the last day, rats were anaesthetised and killed after the collection of aortic
      blood. Small- and large-intestinal mesenteric fat tissues were immediately
      excised, and the release of adiponectin, leptin and TNF-alpha was evaluated from
      the subsequently isolated adipocytes. The weight of the large-intestinal
      mesenteric fat, fasting blood insulin level and homeostatic model assessment for
      insulin resistance decreased in a time-dependent manner, and were much lower in
      the FOS-5wk group than in the control group. These values were correlated with
      aortic blood leptin levels. The secretion rate of leptin from the isolated
      mesenteric adipocytes in the small intestine, but not in the large intestine, was
      lower in the FOS-fed groups than in the control group. In conclusion, FOS feeding
      improved insulin sensitivity accompanied by the reduction in large-intestinal fat
      mass and leptin secretion from the mesenteric adipocytes of the small intestine.

PMID- 21736798
TI  - Accounting for the multidimensional nature of the relationship between adult
      obesity and socio-economic status: the French second National Individual Survey
      on Food Consumption (INCA 2) dietary survey (2006-07).
AB  - The objective was to study the multidimensional nature of the relationship
      between adult obesity (OB) and socio-economic status (SES), using comprehensive
      indices of SES taken separately or synthesised in an overall index. A nationally
      representative sample of adults aged 18-79 years was taken from the French second
      National Individual Survey on Food Consumption (INCA 2) dietary survey (2006-07).
      Weight and height were measured and OB defined as BMI >= 30 kg/m2. SES variables
      were reported in questionnaires and included occupation, education and
      characteristics of household wealth. Composite indices of SES (household wealth
      and overall SES indices) were computed by correspondence analysis, and
      relationships with OB were investigated with logistic regression analysis. In
      total, 11.8 (95 % CI 10.1, 13.4) % of French adults were obese, without
      significant difference by sex. While no significant relationship was observed in
      men, all SES indicators were inversely correlated to OB in women. Both education
      and the household wealth index were retained in the stepwise multivariate model,
      confirming that different socio-economic variables are not necessarily proxies of
      each other regarding the OB issue. On the other hand, 'controlling for SES' while
      including several measures of SES in multivariate models may lead to
      collinearity, and thus over-adjustment. A more integrative approach may be to
      derive a synthetic index by including the SES factors available in a given study.
      Beyond this methodological perspective, understanding how OB is related to the
      different dimensions of SES should help to target the more vulnerable groups and
      increase the effectiveness of prevention.

PMID- 21736799
TI  - Association between calcium in cord blood and newborn size in Bangladesh.
AB  - Ca status in the uterus during pregnancy has been suggested to affect fetal
      growth and size at birth. In Bangladesh, low Ca levels in pregnant women and low
      birth weight in infants are common. The present study explored the association
      between Ca levels in cord blood and newborn size at birth (birth weight and birth
      length) in Bangladesh. Samples and data included 223 women with live-born
      singleton deliveries in rural Bangladesh. Newborn weight and length were measured
      at birth. From cord blood obtained at delivery, Ca, 25-hydroxy vitamin D, bone
      specific alkaline phosphatase and intact parathyroid hormone levels were
      determined. An association between size at birth and Ca levels in cord blood was
      found (birth weight, P = 0.022; birth length, P = 0.001). Associations between Ca
      and newborn size were further analysed using multivariate regression analyses.
      After adjusting for several covariates of characteristics in mothers and newborns
      (gestational weeks at birth, sex of newborn, socio-economic status, maternal
      height, BMI, age and season at birth), birth length still exhibited a significant
      relationship with Ca levels in cord blood (birth length, P = 0.030). The present
      study indicates that Ca status in cord blood might be associated with the birth
      length of newborns. Ca levels during gestation may affect fetal growth.

PMID- 21736800
TI  - Elevated vascular resistance and afterload reduce the cardiac output response to
      dobutamine in early growth-restricted rats in adulthood.
AB  - Epidemiological studies have linked intra-uterine growth restriction (IUGR) with
      an increased risk of CVD later in life. The aim of the present study was to
      examine the effect of maternal protein restriction on cardiac function in
      adulthood during dobutamine (DOB) stimulation. IUGR was induced in Wistar Kyoto
      dams through administration of a low-protein diet (LPD; 8.7 % casein) during
      pregnancy and lactation; the control group received a normal-protein diet (NPD;
      20 % casein). At 14 weeks of age, cardiac function was assessed in male and
      female NPD (eight females and eight males) and LPD offspring (ten females and ten
      males) by pressure volumetry using an anaesthetised closed-chest approach. We
      determined mean arterial pressure (MAP), heart rate and left ventricular pressure
      volume indices under baseline conditions and DOB stimulation (2 and 4 MUg/kg per
      min). During beta-adrenergic activation in LPD offspring, increases in cardiac
      output (CO, P < 0.018) and stroke volume (SV, P < 0.005) were attenuated in
      comparison with NPD offspring, while increases in ejection fraction and the
      maximal rate of ventricular pressure development were not affected. LPD females
      maintained a smaller end-diastolic volume (P < 0.017). MAP did not differ between
      the groups and did not change significantly during DOB infusion. Arterial
      elastance and total peripheral resistance decreased in all rats but remained
      significantly elevated in LPD offspring (P < 0.015 and < 0.01). Early growth
      restriction did not affect ventricular contractility but led to an increased
      afterload and impaired the ability to increase SV and CO during beta-adrenergic
      stimulation.

PMID- 21736801
TI  - Supplementing chicken broth with monosodium glutamate reduces hunger and desire
      to snack but does not affect energy intake in women.
AB  - The effect of monosodium glutamate (MSG) supplementation in soup or broth on
      satiety is not well understood. In the present study, the relative effects of
      four chicken broths with or without added MSG on motivational ratings and energy
      intakes at the next meal were compared using a double-blinded, within-subject
      design. A total of thirty-five normal-weight women, aged 20-40 years, took part
      in four study sessions. The four broths were base chicken broth (63 kJ), broth
      with added MSG (1.19 g) and nucleotides (0.03 g), broth with added MSG (1.22 g),
      and broth with added fat (BAF; 681 kJ). The preloads were presented twice at
      09.00 and 11.15 hours for a maximum cumulative dose of 2.44 g MSG. Motivational
      ratings were collected before and at 15 min intervals post-ingestion for a total
      of 210 min. A test lunch meal was served at 12.00 hours, and plate waste was
      measured. The addition of MSG to chicken broth did not increase energy intakes at
      lunch or affect motivational ratings over the entire testing session. Both hunger
      and desire to snack between the second preload exposure and the test meal were
      significantly reduced in the MSG condition relative to the base broth condition
      (both, P = 0.03). However, only the BAF significantly suppressed energy intakes
      at lunch compared with the base broth control condition. Supplementing chicken
      broth with MSG can increase subjective ratings for satiety but does not alter
      energy intake at the next meal relative to an equal energy broth without added
      MSG.

PMID- 21736802
TI  - Serum 25-hydroxyvitamin D concentrations are associated with erythrocyte levels
      of n-3 PUFA but not risk of CVD.
AB  - Increasing evidence suggests that the status of vitamin D and n-3 PUFA is
      associated with the risk of CVD. Major dietary sources of vitamin D include fish
      and fish products, which are also rich in n-3 PUFA; however, the relationship
      between serum 25-hydroxyvitamin D levels and tissue contents of n-3 PUFA remains
      unknown. The present study investigates the hypothesis that serum 25
      hydroxyvitamin D and erythrocyte n-3 PUFA levels are positively correlated in
      patients with CVD. We recruited sixty CVD cases and matched them with sixty
      healthy controls based on age, sex and season during which blood was drawn for
      the study. As serum 25-hydroxyvitamin D levels increased, erythrocyte levels of
      docosapentaenoic acid, DHA, omega-3 index and total n-3 PUFA increased
      significantly, while erythrocyte levels of stearic acid and total SFA decreased
      significantly, after adjusting for age, sex, BMI and smoking. Partial correlation
      analysis also showed that erythrocyte n-3 PUFA levels were positively correlated
      (r 0.215; P = 0.021) and total SFA content was negatively correlated (r - 0.263;
      P = 0.004) with serum 25-hydroxyvitamin D levels. However, multiple logistic
      regression analysis showed that serum 25-hydroxyvitamin D levels were not
      significantly associated with the risk of CVD, after adjusting or not adjusting
      for age, sex, BMI and smoking. In conclusion, the results of our case-control
      study suggest that serum 25-hydroxyvitamin D levels are positively related to
      erythrocyte n-3 PUFA levels, but are not associated with the risk of CVD in this
      population.

PMID- 21736803
TI  - Habitual sugar intake and cognitive function among middle-aged and older Puerto
      Ricans without diabetes.
AB  - Intake of added sugars, mainly fructose and sucrose, has been associated with
      risk factors for cognitive impairment, such as obesity, the metabolic syndrome
      and type 2 diabetes. The objective of this analysis was to examine whether
      habitual intakes of total sugars, added sugars, sugar-sweetened beverages or
      sweetened solid foods are associated with cognitive function. The present study
      included 737 participants without diabetes, aged 45-75 years, from the Boston
      Puerto Rican Health Study, 2004-9. Cognitive function was measured with a battery
      of seven tests: Mini-Mental State Examination (MMSE), word list learning, digit
      span, clock drawing, figure copying, and Stroop and verbal fluency tests. Usual
      dietary intake was assessed with a validated FFQ. Greater intakes of total
      sugars, added sugars and sugar-sweetened beverages, but not of sugar-sweetened
      solid foods, were significantly associated with lower MMSE score, after adjusting
      for covariates. Adjusted OR for cognitive impairment (MMSE score < 24) were 2.23
      (95 % CI 1.24, 3.99) for total sugars and 2.28 (95 % CI 1.26, 4.14) for added
      sugars, comparing the highest with lowest intake quintiles. Greater intake of
      total sugars was also significantly associated with lower word list learning
      score. In conclusion, higher sugar intake appears to be associated with lower
      cognitive function, but longitudinal studies are needed to clarify the direction
      of causality.

PMID- 21736804
TI  - A high-amylopectin diet caused hepatic steatosis associated with more lipogenic
      enzymes and increased serum insulin concentration.
AB  - Starch is the major energy source for monogastric mammals and humans. The present
      study was conducted to evaluate the liver metabolic responses of weaned pigs fed
      with different dietary starches. A total of sixteen weaned pigs were fed with two
      experimental diets containing either cassava starch (CS, 80 % amylopectin and 20
      % amylose) or maize starch (70 % amylopectin and 30 % amylose). The present
      results showed that the growth performance was not affected by different dietary
      starches (P>0.05). However, ingestion of CS not only increased the lipid content
      in liver tissues, but also elevated the concentrations of serum cholesterol and
      insulin (P < 0.05). The metabolic responses induced by CS were associated with
      more lipogenic enzymes such as fatty acid synthase and 3-hydroxy-3-methyl
      glutaryl-CoA reductase in liver (P < 0.05). Real-time PCR quantification for
      lipid metabolic genes indicated that ingestion of CS not only up-regulated the
      expression of these lipogenic genes, but also decreased the expression of
      lipolytic genes. These results suggested that the metabolic responses of weaned
      pigs fed with different dietary starches may vary widely depending on their
      composition, and ingestion of starches that are high in amylopectin may produce a
      stronger insulinaemic response and lead to an up-regulation of lipogenesis in the
      liver.

PMID- 21736805
TI  - Using a fingertip whole blood sample for rapid fatty acid measurement: method
      validation and correlation with erythrocyte polar lipid compositions in UK
      subjects.
AB  - It is well accepted that n-3 long-chain PUFA intake is positively associated with
      a range of health benefits. However, while benefits have been clearly shown,
      especially for CVD, the mechanisms for prevention/benefit are less understood.
      Analysis of plasma and erythrocyte phospholipids (PL) have been used to measure
      the status of the highly unsaturated fatty acids (HUFA), especially EPA (20 : 5n
      3) and DHA (22 : 6n-3), although the time and complexity of the process places
      limitations on the sample numbers analysed. An assay has been developed using
      whole blood, collected by finger prick, and stored on absorbant paper, subjected
      to direct methylation and fatty acids quantified by automated GC. Tests on fatty
      acid stability show that blood samples are stable when stored at - 20 degrees C
      for 1 month although some loss of HUFA was seen at 4 degrees C. A total of fifty
      one patients, including twenty-seven who consumed no fatty acid supplements,
      provided a blood sample for analysis. Concentrations of all major fatty acids
      were measured in erythrocyte PL and whole blood. The major HUFA, including EPA,
      DHA and arachidonic acid (ARA; 20 : 4n-6), as well as the ARA:EPA ratio and the
      percentage n-3 HUFA/total HUFA all showed good correlations, between erythrocyte
      PL and whole blood. Values of r2 ranged from 0.48 for ARA to 0.95 for the
      percentage of n-3 HUFA/total HUFA. This assay provides a non-invasive, rapid and
      reliable method of HUFA quantification with the percentage of n-3 HUFA value
      providing a potential blood biomarker for large-scale nutritional trials.

PMID- 21736806
TI  - Association of dietary energy density in childhood with age and body fatness at
      the onset of the pubertal growth spurt.
AB  - The aim of the present study was to examine the association of pre-pubertal
      dietary energy density (ED) with both age and body fatness at the start of the
      pubertal growth spurt (age at take-off, ATO). Analyses included 219 DOrtmund
      Nutritional and Anthropometric Longitudinally Designed Study participants with
      sufficient height measurements to estimate ATO who provided 3 d weighed dietary
      records at baseline, i.e. 2 and 3 years before ATO (mean age 6.9 (SD 1.2) years).
      Mean energy intakes and amounts of foods/drinks consumed at baseline were derived
      from the records. ED (kJ/g) was calculated based on (1) all foods and drinks
      (ED_all), (2) foods and energy-containing drinks (ED_energy), (3) foods and milk
      as a drink, but no other beverages (ED_milk) and (4) foods only, solid or liquid
      (ED_food). Using multiple regression analyses, the association between the ED
      variables and ATO was investigated. Furthermore, Z-scores of BMI and fat mass
      index (FMI) at ATO were considered as outcomes to reflect body fatness at puberty
      onset. The results showed that ED at baseline was not associated with ATO,
      regardless of the ED method used. For example, mean ATO in the lowest v. highest
      tertile of ED_food was 9.3 (95 % CI 9.0, 9.5) v. 9.4 (95 % CI 9.1, 9.7) years,
      P(trend) = 0.8 (adjusted for sex, maternal age, birth weight, dietary protein,
      dietary fibre, baseline BMI Z-score). Similarly, ED was not independently
      associated with BMI or FMI Z-score at ATO (P(trend) = 0.3-0.9). In conclusion,
      dietary ED in childhood did not influence timing or body fatness at ATO in this
      cohort of healthy, free-living children.

PMID- 21736807
TI  - The effect of choline and cystine on the utilisation of methionine for protein
      accretion, remethylation and trans-sulfuration in juvenile shrimp Penaeus
      monodon.
AB  - This 35-d feeding experiment examined in juvenile shrimp Penaeus monodon (3.3 g
      initial body weight) the effects of methionine (Met), choline and cystine on
      protein accretion and the activity of two key enzymes of remethylation (betaine
      homocysteine methyltransferase; BHMT) and trans-sulfuration (cystathionine beta
      synthase; CBS). The interaction between Met and choline was tested using semi
      purified diets either adequate or limiting (30 or 50 %) in total sulphur amino
      acid (SAA) content with a constant cystine:Met ratio. The diets contained either
      basal or excess choline (3 v. 7 g/kg feed). Cystine was added to two other 30 and
      50 % Met-limiting diets to adjust the SAA supply to that of the control diet in
      order to evaluate the interaction between Met and cystine. As expected, N
      accretion was significantly lower with the SAA-limiting diets but increased back
      to control levels by the extra choline or cystine, demonstrating their sparing
      effect on Met utilisation for protein accretion. We show, for the first time, the
      activities of BHMT and CBS in shrimp hepatopancreas. Only BHMT responded to the
      SAA deficiencies, whereas the extra choline and cystine did not stimulate
      remethylation or down-regulate trans-sulfuration. Our data also suggest the
      capacity of P. monodon to synthesise taurine, being significantly affected by the
      cystine level in the 30 % SAA-limiting diets. Further research is warranted to
      better understand the metabolic regulation of taurine synthesis in shrimp and of
      the observed Met-sparing effects.

PMID- 21736808
TI  - Comparative effects of dried plum and dried apple on bone in postmenopausal
      women.
AB  - Aside from existing drug therapies, certain lifestyle and nutritional factors are
      known to reduce the risk of osteoporosis. Among the nutritional factors, dried
      plum or prunes (Prunus domestica L.) is the most effective fruit in both
      preventing and reversing bone loss. The objective of the present study was to
      examine the extent to which dried plum reverses bone loss in osteopenic
      postmenopausal women. We recruited 236 women, 1-10 years postmenopausal, not on
      hormone replacement therapy or any other prescribed medication known to influence
      bone metabolism. Qualified participants (n 160) were randomly assigned to one of
      the two treatment groups: dried plum (100 g/d) or dried apple (comparative
      control). Participants received 500 mg Ca plus 400 IU (10 MUg) vitamin D daily.
      Bone mineral density (BMD) of lumbar spine, forearm, hip and whole body was
      assessed at baseline and at the end of the study using dual-energy X-ray
      absorptiometry. Blood samples were collected at baseline, 3, 6 and 12 months to
      assess bone biomarkers. Physical activity recall and 1-week FFQ were obtained at
      baseline, 3, 6 and 12 months to examine physical activity and dietary confounders
      as potential covariates. Dried plum significantly increased BMD of ulna and spine
      in comparison with dried apple. In comparison with corresponding baseline values,
      only dried plum significantly decreased serum levels of bone turnover markers
      including bone-specific alkaline phosphatase and tartrate-resistant acid
      phosphatase-5b. The findings of the present study confirmed the ability of dried
      plum in improving BMD in postmenopausal women in part due to suppressing the rate
      of bone turnover.

PMID- 21736809
TI  - Immunostimulatory effect of faecal Bifidobacterium species of breast-fed and
      formula-fed infants in a peripheral blood mononuclear cell/Caco-2 co-culture
      system.
AB  - Bifidobacterium spp. typical of the human intestinal microbiota are believed to
      influence the balance of immune responses in the intestinal mucosa. The aim of
      the present study was to investigate the effect of different bifidobacterial
      species and their mixtures in in vitro experiments with peripheral blood
      mononuclear cells (PBMC) and Caco-2 cells. Bifidobacterium adolescentis, B.
      angulatum, B. breve, B. catenulatum, B. infantis, B. longum and two combinations
      of these bifidobacteria simulating the species composition found in faecal
      samples from breast-fed (BF) and formula-fed (FF) infants were used. The levels
      of several cytokines were measured by direct stimulation of PBMC and by
      stimulation of a Caco-2/PBMC co-culture with bifidobacteria. B. catenulatum and
      B. breve were the strongest enhancers of interferon-gamma (IFN-gamma) production
      by direct stimulation of PBMC. B. longum was the highest inducer of IL-10 and the
      lowest TNF-alpha stimulus. In the Caco-2/PBMC system, B. breve was the highest
      inducer of IL-8 production by Caco-2 cells, significantly different from B.
      infantis, B. adolescentis and the FF mixture (P < 0.05). IFN-gamma produced by
      PBMC stimulated with the BF mixture (containing 22 % B. breve, compared with 7 %
      in the FF mixture) was significantly higher compared with B. adolescentis, B.
      infantis and B. longum. B. adolescentis also inhibited IFN-gamma production
      compared with the FF mixture and B. longum. The proportion of different
      Bifidobacterium strains seems to be an important determinant of the cytokine
      balance in the simulated intestinal environment studied. B. breve and the
      combination of the Bifidobacterium species typically found in the microbiota of
      BF infants have shown the most significant effects.

PMID- 21736810
TI  - Grape seed extract supplementation prevents high-fructose diet-induced insulin
      resistance in rats by improving insulin and adiponectin signalling pathways.
AB  - Recent evidence strongly supports the contention that grape seed extract (GSE)
      improves hyperglycaemia and hyperinsulinaemia in high-fructose-fed rats. To
      explore the underlying molecular mechanisms of action, we examined the effects of
      GSE on the expression of muscle proteins related to the insulin signalling
      pathway and of mRNA for genes involved in the adiponectin signalling pathway.
      Compared with rats fed on a normal diet, high-fructose-fed rats developed
      pathological changes, including insulin resistance, hyperinsulinaemia,
      hypertriacylglycerolaemia, a low level of plasma adiponectin and a high level of
      plasma fructosamine. These disorders were effectively attenuated in high-fructose
      fed rats supplemented with GSE. A high-fructose diet causes insulin resistance by
      significantly reducing the protein expression of insulin receptor, insulin
      receptor substrate-1, Akt and GLUT4, and the mRNA expression of adiponectin,
      adiponectin receptor R1 (AdipoR1) and AMP-activated protein kinase (AMPK)-alpha
      in the skeletal muscle. Supplementation of GSE enhanced the expression of insulin
      signalling pathway-related proteins, including Akt and GLUT4. GSE also increased
      the mRNA expression of adiponectin, AdipoR1 and AMPK-alpha. In addition, GSE
      increased the mRNA levels of glycogen synthase and suppressed the mRNA expression
      of glycogen synthase kinase-3-alpha, causing an increase in glycogen accumulation
      in the skeletal muscle. These results suggest that GSE ameliorates the defective
      insulin and adiponectin signalling pathways in the skeletal muscle, resulting in
      improved insulin resistance in fructose-fed rats.

PMID- 21736811
TI  - Maternal protein restriction in mice causes adverse metabolic and hypothalamic
      effects in the F1 and F2 generations.
AB  - Maternal protein restriction causes metabolic alterations associated with
      hypothalamic dysfunction. Because the consequences of metabolic programming can
      be passed transgenerationally, the present study aimed to assess whether maternal
      protein restriction alters the expression of hypothalamic neuropeptides in
      offspring and to evaluate hormonal and metabolic changes in male offspring from
      the F1 and F2 generations. Female Swiss mice (F0) were mated and fed either a
      normal-protein (NP group; 19 % protein) or a low-protein (LP group; 5 % protein)
      diet throughout gestation of the F1 generation (NP1 and LP1). At 3 months of age,
      F1 females were mated to produce the F2 generation (NP2 and LP2). Animals from
      all groups were evaluated at 16 weeks of age. LP1 offspring had significantly
      lower weights and shorter lengths than NP1 offspring at birth, but they underwent
      a phase of rapid catch-up growth. Conversely, the LP2 offspring were not
      significantly different from the NP2 offspring in either weight or length. At 16
      weeks, no differences were found in body mass among any of the groups, although
      LP1 and LP2 offspring showed hypercholesterolaemia, hypertriacylglycerolaemia,
      hyperglycaemia, glucose intolerance, insulin resistance, increased levels of
      insulin, leptin and resistin, decreased endogenous leptin sensitivity, increased
      adiposity with elevated leptin levels and leptin resistance characterised by
      altered expression of neuropeptide Y and pro-opiomelanocortin without any changes
      in the leptin receptor Ob-Rb. We conclude that severe maternal protein
      restriction promotes metabolic programming in F1 and F2 male offspring due to a
      dysregulation of the adipoinsular axis and a state of hypothalamic leptin
      resistance.

PMID- 21736812
TI  - Chronic oestrogen replacement in ovariectomised rats attenuates food intake and
      augments c-Fos expression in the suprachiasmatic nucleus specifically during the
      light phase.
AB  - Oestrogen replacement in ovariectomised (OVX) rats has been reported to attenuate
      food intake, especially during the light phase. To gain better insight into the
      central mechanism of oestrogen-induced reduction of food intake, we examined the
      effect of chronic oestrogen replacement in OVX rats on c-Fos expression in the
      suprachiasmatic nucleus (SCN) and on food intake during the light and dark
      phases. Eight-week-old female rats were ovariectomised and implanted with either
      an oestradiol (E2) or a vehicle pellet (Veh) subcutaneously. The animals were
      housed in an environment with a 12 h light-12 h dark cycle with the lights on at
      07.00 hours. The amount of spontaneous food intake relative to each animal's body
      weight was significantly less for the E2 group than for the Veh group during the
      light phase, but there were no differences shown between these groups during the
      dark phase. There were no differences shown in the number of c-Fos-immunoreactive
      cells in the SCN in the E2 group compared with the Veh group during the early
      dark phase (22.00 hours; Zeitgeber time 15.00 (ZT15)), but the number was
      significantly higher than in the Veh group during the early light phase (10.00
      hours; ZT3). This finding suggests that chronic oestrogen replacement chronically
      enhances SCN activity, specifically during the light phase. The oestrogen-induced
      enhancement of SCN activity during the light phase is possibly involved in the
      light phase-specific attenuation of food intake by oestrogen replacement in OVX
      rats.

PMID- 21736813
TI  - Nutrition support in intensive care units in England: a snapshot of present
      practice.
AB  - Nutrition support is an important part of care management in critically ill
      patients, not only to prevent and treat malnutrition but also it has a
      significant impact on recovery from illness and overall outcome. There is little
      information available about present nutritional support practice for patients in
      intensive care units (ICU) in the UK. This survey was designed to evaluate the
      present nutrition support practice in ICU and high dependency units (HDU) in
      England. Data were gathered by a 72 h phone survey from 245 ICU and HDU in 196
      hospitals in England. A questionnaire was completed over the telephone, including
      general information, nutrition support and teams involved in the nutrition
      management in the ICU. Of 1286 total patients in the ICU, 703 (54.6 %) were
      receiving nasogastric feeding, two (1.5 %) were receiving feeding via a
      percutaneous endoscopically placed gastrostomy tube and two (1.5 %) were
      receiving nasojejunal feeding. One hundred and forty-seven (11.4 %) patients were
      on parenteral feeding during the study period. A nutrition support team was not
      available in 158 (83.1 %) ICU and there was no dietitian or specialist nutrition
      nurse to cover ICU in nine (4.7 %) hospitals. In conclusion, the present survey
      reported an increased trend in usage of enteral feeding in ICU in England, and a
      reduction in the use of parenteral nutrition compared with previous surveys.
      However, we are still far from integrating nutrition into care management in the
      ICU.

PMID- 21736814
TI  - Digestive physiological outcomes related to polydextrose and soluble maize fibre
      consumption by healthy adult men.
AB  - The objective of the present study was to evaluate digestive physiological
      outcomes elicited by functional fibres fed to healthy adult men. A total of
      twenty-one healthy adult men were utilised in a cross-over design. Each subject
      received polydextrose (PDX) or soluble maize fibre (SCF) (21 g/d) or no
      supplemental fibre (no fibre control; NFC) in a snack bar. Periods were 21 d and
      faeces were collected during the last 5 d of each period. Food intake, including
      fibre intake, did not differ among treatments. Flatulence (P = 0.001) and
      distention (P = 0.07) were greatest when subjects consumed PDX or SCF. Reflux was
      greater (P = 0.04) when subjects consumed SCF compared with NFC. All tolerance
      scores were low ( < 2.5), indicating only slight discomfort. Faecal ammonia, 4
      methylphenol, indole and branched-chain fatty acid concentrations were decreased
      (P < 0.01) when subjects consumed the functional fibre sources compared with NFC.
      Faecal acetate, propionate and butyrate concentrations were lower (P < 0.05) when
      subjects consumed PDX compared with SCF and NFC. Faecal pH was lower (P = 0.01)
      when subjects consumed SCF compared with NFC, while PDX was intermediate. Faecal
      wet weight was greatest (P = 0.03) when subjects consumed SCF compared with NFC.
      Faecal dry weight tended to be greater (P = 0.07) when subjects consumed PDX
      compared with NFC. The functional fibres led to 1.4 and 0.9 g (PDX and SCF,
      respectively) increases in faecal dry mass per g supplemental fibre intake.
      Bifidobacterium spp. concentrations were greater (P < 0.05) when subjects
      consumed SCF compared with NFC. These functional fibres appear to be beneficial
      to gut health while leading to minimal gastrointestinal upset.

PMID- 21736815
TI  - Viscosity rather than quantity of dietary fibre predicts cholesterol-lowering
      effect in healthy individuals.
AB  - The well-documented lipid-lowering effects of fibre may be related to its
      viscosity, a phenomenon that has been understudied, especially when fibre is
      given against the background of a typical North American (NA) diet. In this three
      arm experiment, we compared the lipid-lowering effect of low-viscosity wheat bran
      (WB), medium-viscosity psyllium (PSY) and a high-viscosity viscous fibre blend
      (VFB), as part of a fibre intervention aimed at increasing fibre intake to
      recommended levels within the context of a NA diet in apparently healthy
      individuals. Using a randomised cross-over design, twenty-three participants
      (twelve males and eleven females; age 35 (SD 12) years; LDL-cholesterol (C) 2.9
      (SEM 0.6) mmol/l) consuming a typical NA diet received a standard, fibre-enriched
      cereal, where approximately one-third of the fibre was either a low-viscosity
      (570 centipoise (cP)) WB, medium-viscosity (14,300 cP) PSY or a high-viscosity
      (136,300 cP) novel VFB, for 3 weeks separated by washout periods of >= 2 weeks.
      There were no differences among the treatments in the amount of food consumed,
      total dietary fibre intake, reported physical activity and body weight. Final
      intake of the WB, PSY and VFB was 10.8, 9.0 and 5.1 g, respectively. Reduction in
      LDL-C was greater with the VFB compared with the medium-viscosity PSY (-12.6 (SEM
      3.5) %, P = 0.002) and low-viscosity WB (-14.6 (SEM 4.2) %, P = 0.003). The
      magnitude of LDL-C reduction showed a positive association with fibre apparent
      viscosity (r - 0.41, P = 0.001). Despite the smaller quantity consumed, the high
      viscosity fibre lowered LDL-C to a greater extent than lower-viscosity fibres.
      These data support the inclusion of high-viscosity fibre in the diet to reduce
      plasma lipids among apparently healthy individuals consuming a typical NA diet.

PMID- 21736816
TI  - Vitamin D status in pregnant Indian women across trimesters and different seasons
      and its correlation with neonatal serum 25-hydroxyvitamin D levels.
AB  - The present cross-sectional study was conducted to determine the vitamin D status
      of pregnant Indian women and their breast-fed infants. Subjects were recruited
      from the Department of Obstetrics, Armed Forces Clinic and Army Hospital
      (Research and Referral), Delhi. A total of 541 apparently healthy women with
      uncomplicated, single, intra-uterine gestation reporting in any trimester were
      consecutively recruited. Of these 541 women, 299 (first trimester, ninety-seven;
      second trimester, 125; third trimester, seventy-seven) were recruited in summer
      (April-October) and 242 (first trimester, fifty-nine, second trimester, ninety
      three; third trimester, ninety) were recruited in winter (November-March) to
      study seasonal variations in vitamin D status. Clinical, dietary, biochemical and
      hormonal evaluations for the Ca-vitamin D-parathormone axis were performed. A
      subset of 342 mother-infant pairs was re-evaluated 6 weeks postpartum. Mean serum
      25-hydroxyvitamin D (25(OH)D) of pregnant women was 23.2 (SD 12.2) nmol/l.
      Hypovitaminosis D (25(OH)D < 50 nmol/l) was observed in 96.3 % of the subjects.
      Serum 25(OH)D levels were significantly lower in winter in the second and third
      trimesters, while serum intact parathormone (iPTH) and alkaline phosphatase
      levels were significantly higher in winter in all three trimesters. A significant
      negative correlation was found between serum 25(OH)D and iPTH in mothers (r -
      0.367, P = 0.0001) and infants (r - 0.56, P = 0.0001). A strong positive
      correlation was observed between 25(OH)D levels of mother-infant pairs (r 0.779,
      P = 0.0001). A high prevalence of hypovitaminosis D was observed in pregnancy,
      lactation and infancy with no significant inter-trimester differences in serum
      25(OH)D levels.

PMID- 21736817
TI  - Dietary protein and energy supplies differentially affect resistance to parasites
      in lactating mammals.
AB  - Periparturient relaxation of immunity (PPRI) to parasites in mammals results in
      higher worm burden and worm egg excretion and may have a nutritional basis.
      Nippostrongylus brasiliensis re-infected lactating rats fed low-crude protein
      (CP) diets show an augmented degree of PPRI compared with their high CP-fed
      counterparts. However, such effects of CP scarcity have been confounded by
      metabolisable energy (ME) scarcity due to increased intake of the high-CP foods.
      Here, we independently assessed the effects of dietary CP and ME scarcity on the
      degree of PPRI. Second, parity rats were infected with N. brasiliensis larvae
      before mating. Upon parturition, dams were allocated to one of six feeding
      treatments (1-6), consisting of two levels of dietary ME supply, each with three
      levels of CP supply. On day 2 of lactation, dams were either re-infected with
      1600 N. brasiliensis larvae or sham-infected with PBS, while litter size was
      standardised at ten pups. Dams and litters were weighed daily until either day 8
      or 11 of lactation, when worm burdens were assessed as a proxy for PPRI.
      Increased CP and ME supply independently improved lactational performance. While
      ME supply did not affect parasitism, increasing CP supply reduced worm burden and
      the percentage of female worms in the small intestine; the latter was especially
      pronounced at the lower level of ME supply. The present results support the view
      that PPRI to parasites may be sensitive to CP scarcity, but not to moderate ME
      scarcity.

PMID- 21736818
TI  - Taurine supplementation restored the changes in pancreatic islet mitochondria in
      the fetal protein-malnourished rat.
AB  - Intra-uterine growth retardation has been linked to the development of type 2
      diabetes in later life. Mitochondrial changes have been suggested as a link
      between fetal malnutrition and adult insulin resistance. Taurine has been
      implicated in this process. We investigated whether protein malnutrition in early
      life alters mitochondria of the pancreatic islets in adulthood, and whether
      taurine supplementation restores these changes. Male offspring of rats fed a
      control diet, a low-protein diet or a low-protein diet supplemented with taurine
      during pregnancy and lactation were weaned onto the control diet. In each group,
      at 20 weeks of age, intravenous glucose tolerance tests, euglycaemic
      hyperinsulinaemic clamp studies, morphometric analysis of the pancreatic islets
      and ultra-structural analysis of the mitochondria of the beta-cells were
      performed. The expressions of cytochrome c oxidase (COX) I and mitochondrial
      respiratory chain complex II were also measured. Fetal protein-malnourished rats
      showed decreased pancreatic islet mass and reduced insulin-secretory responses to
      a glucose load. These rats also showed reduced mitochondrial DNA-encoded COX I
      gene expression in the islets. Electron microscopic examination showed abnormal
      mitochondrial shapes in the beta-cells of fetal protein-malnourished rats.
      Taurine supplementation to the low-protein diet restored all these changes. Our
      findings indicate that a maternal protein-restriction diet causes long-lasting
      mitochondrial changes that may contribute to the development of type 2 diabetes
      later in life. The lack of taurine may be a key causative factor for these
      dysfunctional mitochondrial changes.

PMID- 21736819
TI  - In vitro and in vivo evaluation of the anticarcinogenic and cancer
      chemopreventive potential of a flavonoid-rich fraction from a traditional Indian
      herb Selaginella bryopteris.
AB  - Prevention of cancer through nutritional intervention has gained significant
      recognition in recent years. Evidence revealed from mechanistic investigations
      coupled with molecular epidemiology show an inverse association of dietary
      flavonoids intake with cancer risk. The chemopreventive and anticarcinogenic
      potential of Selaginella bryopteris, a traditional Indian herb referred to as
      'Sanjeevani' in the Ayurvedic system of medicine, was examined in the present
      study. Comprehensive in vitro and in vivo studies were conducted on the flavonoid
      rich benzene fraction of the aqueous extract that demonstrated a significant
      cytoprotective activity. Biomarkers of chemoprevention such as proliferative
      index and status of cell-cycle regulatory proteins, antioxidant property, anti
      inflammatory effect, reversal of stress-induced senescence and genoprotective
      effect were investigated in human and murine cell cultures. Chemopreventive
      potential was assessed in benzopyrene-induced lung carcinogenesis and 7,12
      dimethyl benz(a)anthracene-mediated skin papillomagenesis test models. Inhibition
      of DNA fragmentation, unperturbed cell-cycle regulation, maintenance of
      intracellular antioxidant defence, anti-inflammatory activity, prevention of
      stress-induced senescence and genoprotective effects against methyl isocyanate
      carcinogenicity was observed. Medium-term anticarcinogenicity and two-stage skin
      papillomagenesis tests strongly substantiated our in vitro observations. Results
      from the present study provide evidence of anticarcinogenic and chemopreventive
      activities of S. bryopteris hitherto unreported and reaffirm the nutritional
      significance of flavonoids in cancer prevention.

PMID- 21736820
TI  - Impact of low v. moderate intakes of long-chain n-3 fatty acids on risk of
      coronary heart disease.
AB  - The objective of the present study was to determine whether the consumption of >=
      250 v. < 250 mg of the long-chain n-3 fatty acids (n-3 LCFA) per d is associated
      with a reduction in the risk of fatal and non-fatal CHD in individuals with no
      prior history of CHD. A comprehensive and systematic review of the published
      scientific literature resulted in the identification of eight prospective studies
      (seven cohorts and one nested case-control study) that met predefined inclusion
      criteria. Relative to the consumption of < 250 mg n-3 LCFA per d, the consumption
      of >= 250 mg/d was associated with a significant 35.1 % reduction in the risk of
      sudden cardiac death and a near-significant 16.6 % reduction in the risk of total
      fatal coronary events, while the risk of non-fatal myocardial infarction was not
      significantly reduced. In several meta-analyses, which were based on US studies,
      risk of CHD death was found to be dose-dependently reduced by the n-3 LCFA, with
      further risk reductions observed with intakes in excess of 250 mg/d. Prospective
      observational and intervention data from Japan, where intake of fish is very
      high, suggest that n-3 LCFA intakes of 900 to 1000 mg/d and greater may confer
      protection against non-fatal myocardial infarction. Thus, the intake of 250 mg n
      3 LCFA per d may, indeed, be a minimum target to be achieved by the general
      population for the promotion of cardiovascular health.

PMID- 21736821
TI  - Activation of PPARgamma and delta by dietary punicic acid ameliorates intestinal
      inflammation in mice.
AB  - The goal of the present study was to elucidate the mechanisms of immunoregulation
      by which dietary punicic acid (PUA) prevents or ameliorates experimental
      inflammatory bowel disease (IBD). The expression of PPARgamma and delta, their
      responsive genes and pro-inflammatory cytokines was assayed in the colonic
      mucosa. Immune cell-specific PPARgamma null, PPARdelta knockout and wild-type
      mice were treated with PUA and challenged with 2.5 % dextran sodium sulphate
      (DSS). The prophylactic efficacy of PUA was examined in an IL-10(-/-) model of
      IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also
      examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis
      in IL-10(-/-) mice and DSS colitis, up-regulated Foxp3 expression in Treg and
      suppressed TNF-alpha, but the loss of functional PPARgamma or delta impaired
      these anti-inflammatory effects. At the cellular level, the macrophage-specific
      deletion of PPARgamma caused a complete abrogation of the protective effect of
      PUA, whereas the deletion of PPARdelta or intestinal epithelial cell-specific
      PPARgamma decreased its anti-inflammatory efficacy. We provide in vivo molecular
      evidence demonstrating that PUA ameliorates experimental IBD by regulating
      macrophage and T-cell function through PPARgamma- and delta-dependent mechanisms.

PMID- 21736822
TI  - Nutrient-based standards for school lunches complement food-based standards and
      improve pupils' nutrient intake profile.
AB  - Following concerns about the nutritional content of school lunches and the
      increased prevalence of overweight and obesity in the UK, changes to the
      standards of school meals were made. From September 2008, all primary schools in
      England were required, by law, to be fully compliant with the new food-based
      standards (FBS) and nutrient-based standards (NBS) for school lunches. The aim of
      the present survey was to evaluate the introduction of the NBS for school lunches
      on the nutritional profile of food and drink items provided by schools and chosen
      by pupils at lunchtime. A nationally representative sample of 6696 pupils from
      136 primary schools in England aged 3-12 years and having school lunches was
      recruited. Data were collected on lunchtime food and drink provision at each
      school and on pupil food and drink choices at lunchtime. Caterers also provided
      planned menus, recipes and other cooking information. Compliance with both the
      FBS and NBS was then assessed. Results show that even when the FBS was met, many
      schools did not provide a school lunch that met the NBS as well. The average
      school lunch eaten was significantly lower in fat, saturated fat and Na in
      schools that met both the FBS and NBS for school lunches compared with schools
      that met only the FBS. Change in school lunch policy has contributed to
      improvements in pupils' choices and the nutritional profile of foods selected at
      lunchtime.

PMID- 21736823
TI  - Polysaccharide from Gynura divaricata modulates the activities of intestinal
      disaccharidases in streptozotocin-induced diabetic rats.
AB  - During diabetes, structural and functional changes in the alimentary tract are
      known to take place resulting in an increased absorption of intestinal glucose
      and alterations in the activities of brush-border disaccharidases. To elucidate
      the effect of administrating polysaccharide from Gynura divaricata (PGD) on
      disaccharidase activities, the specific activities of intestinal disaccharidases,
      namely sucrase, maltase and lactase, were measured in streptozotocin-induced
      diabetic rats. Normal control and diabetic rats were treated by oral
      administration with PGD. Specific activities of intestinal disaccharidases were
      increased significantly during diabetes, and amelioration of the activities of
      sucrase and maltase during diabetes was clearly visible by the treatment with
      PGD. However, the increased activity of lactase during diabetes mellitus was
      remarkably alleviated by the administration of PGD only in the duodenum.
      Meanwhile, oral sucrose tolerance tests demonstrated that PGD alleviated the
      hyperglycaemia during diabetes mellitus, resulting from the amelioration in the
      activities of intestinal disaccharidases. The present investigation suggests that
      PGD exerted an anti-diabetic effect partly via inhibiting the increased
      intestinal disaccharidase activities of diabetic rats. This beneficial influence
      of administration of PGD on intestinal disaccharidases clearly indicates their
      helpful role in the management of diabetes.

PMID- 21736824
TI  - Ethnic differences in the relationship between body mass index and percentage
      body fat among Asian children from different backgrounds.
AB  - Overweight and obesity in Asian children are increasing at an alarming rate;
      therefore a better understanding of the relationship between BMI and percentage
      body fat (%BF) in this population is important. A total of 1039 children aged 8
      10 years, encompassing a wide BMI range, were recruited from China, Lebanon,
      Malaysia, The Philippines and Thailand. Body composition was determined using the
      2H dilution technique to quantify total body water and subsequently fat mass, fat
      free mass and %BF. Ethnic differences in the BMI-%BF relationship were found; for
      example, %BF in Filipino boys was approximately 2 % lower than in their Thai and
      Malay counterparts. In contrast, Thai girls had approximately 2.0 % higher %BF
      values than in their Chinese, Lebanese, Filipino and Malay counterparts at a
      given BMI. However, the ethnic difference in the BMI-%BF relationship varied by
      BMI. Compared with Caucasian children of the same age, Asian children had 3-6
      units lower BMI at a given %BF. Approximately one-third of the obese Asian
      children (%BF above 25 % for boys and above 30 % for girls) in the study were not
      identified using the WHO classification and more than half using the
      International Obesity Task Force classification. Use of the Chinese
      classification increased the sensitivity. Results confirmed the necessity to
      consider ethnic differences in body composition when developing BMI cut-points
      and other obesity criteria in Asian children.

PMID- 21736825
TI  - Consumption of salmon v. salmon oil capsules: effects on n-3 PUFA and selenium
      status.
AB  - Salmon provides long-chain (LC) n-3 PUFA and Se, which are well recognised for
      their health benefits. The n-3 and Se status of the New Zealand population is
      marginal. The objective of the present study was to compare the effects of
      consuming salmon v. supplementation with salmon oil on LC n-3 and Se status.
      Healthy volunteers (n 44) were randomly assigned to one of four groups consuming
      2 * 120 g servings of salmon/week or 2, 4 or 6 salmon oil capsules/d for 8 weeks.
      Linear regression analysis predictive models were fitted to the capsule data to
      predict changes in erythrocyte LC n-3 levels with intakes of LC n-3 from capsules
      in amounts equivalent to that consumed from salmon. Changes in Se status (plasma
      Se and whole-blood glutathione peroxidase) were compared between the groups
      consuming salmon and capsules (three groups combined). Salmon, 2, 4 and 6
      capsules provided 0.82, 0.24, 0.47 and 0.69 g/d of LC n-3 fatty acids. Salmon
      provided 7 MUg/d and capsules < 0.02 MUg/d of Se. The predictive model (r(2)
      0.31, P = 0.001) showed that increases in erythrocyte LC n-3 levels were similar
      when intakes of 0.82 g/d LC n-3 from salmon or capsules (1.92 (95 % CI 1.35,
      2.49) v. 2.32 (95 % 1.76, 2.88) %) were consumed. Plasma Se increased
      significantly more with salmon than with capsules (12.2 (95 % CI 6.18, 18.12) v.
      1.57 (95 % CI - 2.32, 5.45) MUg/l, P = 0.01). LC n-3 status was similarly
      improved with consumption of salmon and capsules, while consuming salmon had the
      added benefit of increasing Se status. This is of particular relevance to the New
      Zealand population that has marginal LC n-3 and Se status.

PMID- 21736826
TI  - Glutamine supplementation improves intestinal barrier function in a weaned piglet
      model of Escherichia coli infection.
AB  - The weaning period is associated with an increased prevalence of gastrointestinal
      infection in many species. Glutamine (Gln) has been shown to improve intestinal
      barrier function and immune function in both in vivo and in vitro models. The
      objective of the present study was to determine the effect of dietary Gln
      supplementation on intestinal barrier function and intestinal cytokines in a
      model of Escherichia coli infection. We randomised 21-d-old piglets (n 20) to
      nutritionally complete isonitrogenous diets with or without Gln (4.4 %, w/w) for
      2 weeks. Intestinal loops were isolated from anaesthetised pigs and inoculated
      with either saline or one of the two E. coli (K88AC or K88 wild-type)-containing
      solutions. Intestinal tissue was studied for permeability, cytokine expression,
      fluid secretion and tight-junction protein expression. Animals receiving Gln
      supplementation had decreased potential difference (PD) and short-circuit current
      (I(sc)) in E. coli-inoculated intestinal loops (PD 0.628 (SEM 0.151) mV; I(sc)
      13.0 (SEM 3.07) MUA/cm(2)) compared with control-fed animals (PD 1.36 (SEM 0.227)
      mV; I(sc) 22.4 (SEM 2.24) MUA/cm(2)). Intestinal tissue from control, but not
      from Gln-supplemented, animals responded to E. coli with a significant increase
      in mucosal cytokine mRNA (IL-1beta, IL-6, transforming growth factor-beta and IL
      10). Tight-junction protein expression (claudin-1 and occludin) was reduced with
      exposure to E. coli in control-fed animals and was not influenced in Gln
      supplemented piglets. Gln supplementation may be useful in reducing the severity
      of weaning-related gastrointestinal infections, by reducing the mucosal cytokine
      response and altering intestinal barrier function.

PMID- 21736827
TI  - Protecting the bowel of premature infants.

PMID- 21736828
TI  - The addition of raspberries and blueberries to a starch-based food does not alter
      the glycaemic response.
AB  - It is now known that health benefits associated with diets rich in fruit and
      vegetables may be partly derived from intake of polyphenols. Berry polyphenols
      may influence carbohydrate metabolism and absorption and hence postprandial
      glycaemia. To date, studies related to polyphenol effects on the glycaemic
      response have been completed only in liquids using either monosaccharides or
      disaccharides. It remains to be determined whether berries known to be rich in
      polyphenols can reduce the glycaemic response (GR) to a solid polysaccharide
      meal. The aim of the present study was to investigate whether berries alter
      postprandial hyperglycaemia and consequently the GR to a starchy food. Blood
      glucose was tested on seven occasions, on three occasions using a reference food
      and on four occasions using pancakes supplemented with either raspberries or
      blueberries or control pancakes containing similar amounts of fructose and
      glucose. Results showed that there were no differences in GR (blueberry 51.3 (SEM
      5.7); raspberry 54.7 (SEM 5.6); blueberry control 43.9 (SEM 4.2); raspberry
      control 41.8 (SEM 6.4)), GR area under the curve or satiety index between any of
      the tests. The present study indicates that the ability of berries to reduce
      blood glucose from starch-based foods is unsubstantiated.

PMID- 21736829
TI  - Gene-PUFA interactions and obesity risk.
AB  - Although there are indications for modulatory effects of PUFA on associations
      between SNP and obesity risk, scientific evidence in human subjects is still
      scarce. The present analyses investigated interaction effects between SNP in
      candidate genes for obesity and PUFA in erythrocyte membranes on obesity risk.
      Within the second Bavarian Food Consumption Survey (cross-sectional, population
      based), 568 adults provided blood samples. Fatty acid composition of erythrocyte
      membranes was analysed by means of GC. Genotyping was performed for twenty-one
      genes, including cytokines, adipokines, neurotransmitters and transcription
      factors. In addition, plasma IL-6 concentrations were analysed. For the
      statistical analysis, a logistic regression model assuming additive genetic
      effects was chosen. About 20 % of the study participants were classified as obese
      (BMI >= 30 kg/m(2)). Several significant gene-PUFA interactions were found,
      indicating regulatory effects of PUFA by gene variants of IL-2, IL-6, IL-18, TNF
      receptor family member 1B and 21, leptin receptor and adiponectin on obesity
      risk. After stratification by genotype, the strongest effects were found for
      rs2069779 (IL-2) and all tested PUFA as well as for rs1800795 (IL-6) and linoleic
      or arachidonic acid. The obesity risk of minor allele carriers significantly
      decreased with increasing fatty acid content. The genetic PUFA-IL-6 interaction
      was also reflected in plasma IL-6 concentrations. If replicated in a prospective
      study with sufficient statistical power, the results would indicate a beneficial
      effect of high PUFA supply for a substantial proportion of the population with
      respect to obesity risk.

PMID- 21736830
TI  - A potential role of IL-6 in the chito-oligosaccharide-mediated inhibition of
      adipogenesis.
AB  - Recent studies have suggested that chito-oligosaccharides can have anti
      adipogenic properties. The objectives of the present study were to evaluate the
      anti-adipogenic potential of four different chito-oligosaccharides (molecular
      weight (MW) < 1000, 1000-3000, 3000-5000 and 5000-10,000 Da) and to identify
      molecular mechanisms underlying the chito-oligosaccharide-mediated inhibition of
      adipogenesis. Mouse 3T3-L1 cells were allowed to differentiate in the presence of
      chito-oligosaccharide. At day 8 post-induction of differentiation, lipid
      accumulation, free glycerol release and the quantitative expression of adipogenic
      marker genes were evaluated. Chito-oligosaccharides had concentration- and MW
      dependent inhibitory effects on lipid accumulation (P < 0.001 and < 0.05,
      respectively), as well as a concentration-dependent effect (P < 0.001) on free
      glycerol release and the expression of adipogenic marker genes. The 5000-10,000
      Da chito-oligosaccharide was selected for subsequent molecular studies. A panel
      of forty-four lipid metabolic pathway-specific genes was analysed by quantitative
      real-time PCR. Chito-oligosaccharide-mediated inhibition of adipogenesis was
      associated with the up-regulation of the IL-6 gene at all concentrations of chito
      oligosaccharide examined and the PG-endoperoxide synthase 2 (PTGS2) gene at
      higher concentrations of chito-oligosaccharide. The effect of chito
      oligosaccharide on gene expression was validated by measuring IL-6 protein
      concentrations in the media. Finally, an IL-6 promoter assay was developed to
      characterise the effect of chito-oligosaccharide on the transcriptional activity
      of the IL-6 promoter, which was increased in a concentration-dependent manner (P
      < 0.001). We conclude that IL-6 is a candidate signalling molecule in the chito
      oligosaccharide-mediated inhibition of adipogenesis in 3T3-L1 cells.

PMID- 21736831
TI  - Dietary glycaemic index and glycaemic load among Australian children and
      adolescents.
AB  - There are no published data regarding the overall dietary glycaemic index (GI)
      and glycaemic load (GL) of Australian children and adolescents. We therefore aim
      to describe the dietary GI and GL of participants of the 2007 Australian National
      Children's Nutrition and Physical Activity Survey (2007ANCNPAS), and to identify
      the main foods contributing to their GL. Children, aged 2-16 years, who provided
      two 24 h recalls in the 2007ANCNPAS were included. A final dataset of 4184
      participants was analysed. GI of each food item was assigned using a previously
      published method. GL was calculated, and food groups contributing to the GL were
      described by age group and sex. The weighted mean dietary GI and GL of the
      participants were 54 (SD 5) and 136 (SD 44), respectively. Among the nutrients
      examined, Ca had the highest inverse relationship with GI (P < 0.001), while
      percentage energy from starch was most positively associated with GI. The
      association between fibre density and GI was modest, and percentage energy from
      sugar had an inverse relationship with GI. Daily dietary GL contributed by energy
      dense and/or nutrient-poor (EDNP) items in subjects aged 14-16 years was more
      than doubled that of subjects aged 2-3 years. To conclude, Australian children
      and adolescents were having a high-GI dietary pattern characterised by high
      starchy food intake and low Ca intake. A significant proportion of their dietary
      GL was from EDNP foods. Efforts to reduce dietary GI and GL in children and
      adolescents should focus on energy-dense starchy foods.

PMID- 21736832
TI  - Hepcidin expression in the liver of rats fed a magnesium-deficient diet.
AB  - Mg deficiency accelerates Fe accumulation in the liver, which may induce various
      metabolic disturbances. In the present study, we examined the gene expression of
      Hepcidin, a peptide hormone produced in the liver to regulate intestinal Fe
      absorption negatively, in Mg-deficient rats. Although liver Fe concentration was
      significantly higher in rats fed an Mg-deficient diet for 4 weeks than in rats
      fed a control diet, Hepcidin expression in the liver was comparable between the
      dietary groups. Previous studies revealed that Fe overload up-regulated Hepcidin
      expression through transcriptional activation by Fe-induced bone morphogenetic
      protein (Bmp) 6, a growth/differentiation factor belonging to the transforming
      growth factor-beta family, in the liver. Mg deficiency up-regulated the
      expression of Bmp6 but did not affect the expression of inhibition of DNA binding
      1, a sensitive Bmp-responsive gene. In addition, the expression of Bmp receptors
      such as activin receptor-like kinase 2 (Alk2), activin receptor type IIA
      (Actr2a), activin receptor type IIB (Actr2b) and Bmp type II receptor (Bmpr2) was
      lower in the liver of Mg-deficient rats than in that of control rats. The present
      study indicates that accumulation of hepatic Fe by Mg deficiency is a stimulant
      inducing Bmp6 expression but not Hepcidin expression by blunting Bmp signalling
      possibly resulting from down-regulation of the receptor expression. Unresponsive
      Hepcidin expression may have a role in Mg deficiency-induced changes related to
      increased liver Fe.

PMID- 21736833
TI  - A cross-sectional study on trans-fatty acids and risk markers of CHD among middle
      aged men representing a broad range of BMI.
AB  - Intake of trans-fatty acids (TFA), especially industrially produced TFA (I-TFA),
      has been associated with the risk of CHD through influence on serum lipid levels.
      Other causal pathways remain less investigated. In the present cross-sectional
      study of middle-aged men representing a broad range of BMI, the association
      between intake of TFA, I-TFA and ruminant TFA (R-TFA) and obesity-associated risk
      markers of CHD was assessed. The study comprised 393 Danish men (median age 49
      years) with a median BMI of 28.4 kg/m(2). Intake of TFA was estimated based on 7
      d dietary records, whereas outcomes of interest (waist circumference, sagittal
      abdominal diameter, percentage of truncal fat, C-reactive protein, IL-6, blood
      lipids, blood pressure, HbA1c and insulin sensitivity index) were obtained
      through clinical examination. The associations were assessed by linear regression
      analysis. The median intake of total TFA among the 393 men was 1.3 g/d, covering
      a daily I-TFA intake of 0.4 g (10-90th percentile 0.0-1.0) and R-TFA intake of
      0.9 g (10-90th percentile 0.4-1.8). Intake of these amounts of TFA showed no
      significant associations with abdominal fatness, inflammatory markers, blood
      lipids, blood pressure and insulin homeostasis. Among middle-aged men with a
      generally low intake of TFA, neither I-TFA nor R-TFA was significantly related to
      obesity-associated risk markers of CHD. The decreased average intake of I-TFA in
      Denmark since 1995 is suggested to effectively prevent occurrence of the adverse
      metabolic changes and health consequences, which have formerly been observed in
      relation to, especially, I-TFA intake.

PMID- 21736834
TI  - Adherence to the Mediterranean diet reduces mortality in the Spanish cohort of
      the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain).
AB  - Epidemiological studies show that adherence to a Mediterranean diet (MD)
      increases longevity; however, few studies are restricted to Mediterranean
      populations or explore the effect of a MD pattern that directly incorporates
      olive oil. Therefore the relationship between adherence to the MD and mortality
      was studied within the the Spanish cohort of the European Prospective
      Investigation into Cancer and Nutrition (EPIC-Spain). The EPIC-Spain analysis
      included 40 622 participants (37.7 % males) aged 29-69 years who were recruited
      from five Spanish regions in 1992-1996. During a mean follow-up of 13.4 years,
      1855 deaths were documented: 913 from cancer, 399 from CVD, 425 from other causes
      and 118 from unknown causes of death. Risk of all-cause and cause-specific
      mortality was assessed according to the level of adherence to a relative MD
      (rMED) score, measured using an 18-unit scale incorporating nine selected dietary
      components. A high compared with a low rMED score was associated with a
      significant reduction in mortality from all causes (hazard ratio (HR) 0.79; 95 %
      CI 0.69, 0.91), from CVD (HR 0.66; 95 % CI 0.49, 0.89), but not from overall
      cancer (HR 0.92; 95 % CI 0.75, 1.12). A 2-unit increase in rMED score was
      associated with a 6 % (P < 0.001) decreased risk of all-cause mortality. A high
      olive oil intake and moderate alcohol consumption contributed most to this
      association. In this Spanish cohort, following an olive oil-rich MD was related
      to a significant reduction in all-cause mortality, and reduced the risk of
      mortality from CVD. These results support the important role that the MD pattern
      has on reducing mortality in Mediterranean countries.

PMID- 21736835
TI  - Association between dietary phyto-oestrogens and bone density in men and
      postmenopausal women.
AB  - Phyto-oestrogens have been associated with a decreased risk for osteoporosis, but
      results from intervention and observational studies in Western countries have
      been inconsistent. In the present study, we investigated the association between
      habitual phyto-oestrogen intake and broadband ultrasound attenuation (BUA) of the
      calcanaeum as a marker of bone density. We collected 7 d records of diet, medical
      history and demographic and anthropometric data from participants (aged 45-75
      years) in the European Prospective Investigation into Cancer-Norfolk study. Phyto
      oestrogen (biochanin A, daidzein, formononetin; genistein, glycitein;
      matairesinol; secoisolariciresinol; enterolactone; equol) intake was determined
      using a newly developed food composition database. Bone density was assessed
      using BUA of the calcanaeum. Associations between bone density and phyto
      oestrogen intake were investigated in 2580 postmenopausal women who were not on
      hormone replacement therapy and 4973 men. Median intake of total phyto-oestrogens
      was 876 (interquartile range 412) MUg/d in postmenopausal women and 1212
      (interquartile range 604) MUg/d in men. The non-soya isoflavones formononetin and
      biochanin A were marginally significant or significantly associated with BUA in
      postmenopausal women (beta = 1.2; P < 0.1) and men (beta = 1.2; P < 0.05),
      respectively; enterolignans and equol were positively associated with bone
      density in postmenopausal women, but this association became non-significant when
      dietary Ca was added to the model. In the lowest quintile of Ca intake, soya
      isoflavones were positively associated with bone density in postmenopausal women
      (beta = 1.4; P < 0.1). The present results therefore suggest that non-soya
      isoflavones are associated with bone density independent of Ca, whereas the
      association with soya or soya isoflavones is affected by dietary Ca.

PMID- 21736836
TI  - Relation of body composition to daily physical activity in free-living Japanese
      adult women.
AB  - The objective of the present study was to investigate the relationship between
      the indices of body size such as BMI, fat-free mass index (FFMI, FFM/height2),
      fat mass index (FMI, FM/height2), and body fat percentage (%BF), and physical
      activities assessed by the doubly-labelled water (DLW) method and an
      accelerometer in free-living Japanese adult women. We conducted a cross-sectional
      study in 100 female subjects ranging in age from 31 to 69 years. Subjects were
      classified in quartiles of BMI, FFMI, FMI and %BF. Daily walking steps and the
      duration of light to vigorous physical activity were simultaneously assessed by
      an accelerometer for the same period as the DLW experiment. Only physical
      activity-related energy expenditure (PAEE)/FFM and PAEE/body weight (BW)
      decreased in the highest quartile of BMI. Physical activity level, PAEE/FFM and
      PAEE/BW decreased in the highest quartile of FMI and %BF, whereas they were not
      different among quartiles of FFMI. Daily walking steps and the duration of
      moderate- and vigorous-intensity physical activities decreased or tended to
      decrease in the highest quartile of FMI and %BF, but did not differ among
      quartiles of FFMI and BMI. These results clearly showed that Japanese adult women
      with higher fat deposition obviously had a low level of physical activities
      assessed by both the DLW method and accelerometry, but those with larger BMI had
      lower PAEE/FFM and PAEE/BW only. Our data suggest that the relationship between
      obesity and daily physical activities should be discussed using not only BMI but
      also FMI or %BF.

PMID- 21736837
TI  - Olive oil supplemented with menaquinone-7 significantly affects osteocalcin
      carboxylation.
AB  - Menaquinone-7 (MK-7), a member of the vitamin K2 family, performs several
      functions, all related to its recognised effect on post-translational
      carboxylation of certain protein-bound glutamate residues. Due to its lipophilic
      structure MK-7 is soluble in olive oil, so the aim of the present study was to
      test whether extra-virgin (EV) olive oil enriched with MK-7 significantly
      increases MK-7 plasma levels and has an effect on osteocalcin and its
      carboxylation status. Healthy young volunteers (n 12) were administered 20 ml EV
      olive oil per d for 2 weeks, followed by 2 weeks of the same amount of olive oil
      enriched with 45 MUg and then 90 MUg MK-7, with an appropriate washout time in
      between. Blood was collected and plasma separated in each phase of the study. We
      found that integration of the diet with EV olive oil alone did not produce any
      significant variation of MK-7 plasma levels compared with baseline.
      Supplementation with MK-7-enriched olive oil resulted in a significant and dose
      dependent increase in plasma levels. The high dose also significantly increased
      carboxylated osteocalcin (cOC) and decreased undercarboxylated osteocalcin (ucOC)
      plasma levels, resulting in a significant increase in the cOC:ucOC ratio. A
      significant correlation was also found between percentage variation of plasma
      cOCA:ucOC ratio and increase in plasma MK-7 levels. We conclude that regular
      consumption of MK-7-enriched olive oil may constitute a valid approach in order
      to preserve some key biochemical mechanisms controlling bone mineralisation.

PMID- 21736838
TI  - Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25
      dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional
      analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening
      Trial.
AB  - Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However,
      because studies examining the associations of all three chronic conditions with
      circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D
      (1,25(OH)(2)D) are limited, we examined these associations in the US Prostate,
      Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian
      PLCO participants selected as controls in previous nested case-control studies of
      25(OH)D and 1,25(OH)(2)D were included in this analysis. Diabetes, CHD and
      hypertension prevalence, risk factors for these conditions and intake of vitamin
      D and Ca were collected from a baseline questionnaire. Results indicated that
      serum levels of 25(OH)D were low (< 50 nmol/l) in 29 % and very low (< 37 nmol/l)
      in 11 % of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30
      and 10 %, respectively. After adjustment for confounding by sex, geographical
      location, educational level, smoking history, BMI, physical activity, total
      dietary energy and vitamin D and Ca intake, only diabetes was significantly
      associated with lower 25(OH)D and 1,25(OH)(2)D levels. Caucasians who had 25(OH)D
      >= 80 nmol/l were half as likely to have diabetes (OR 0.5 (95 % CI 0.3, 0.9))
      compared with those who had 25(OH)D < 37 nmol/l. Those in the highest quartile of
      1,25(OH)(2)D (>= 103 pmol/l) were less than half as likely to have diabetes (OR
      0.3 (95 % CI 0.1, 0.7)) than those in the lowest quartile (< 72 pmol/l). In
      conclusion, the independent associations of 25(OH)D and 1,25(OH)(2)D with
      diabetes prevalence in a large population are new findings, and thus warrant
      confirmation in larger, prospective studies.

PMID- 21736839
TI  - Dietary patterns are associated with cardiometabolic risk factors in a
      representative study population of German adults.
AB  - Studies that investigated complex actual eating behaviours of the general
      population and their relation to cardiometabolic risk markers are sparse. We
      aimed to identify dietary patterns within a nationally representative sample of
      4025 German adults by factor analysis based on validated dietary history
      interviews. Furthermore, we evaluated associations of the derived dietary
      patterns with abnormalities clustered within the metabolic syndrome and related
      metabolic markers by logistic regression models and ANCOVA. A high adherence to
      the 'processed foods' pattern reflected a high intake of refined grains,
      processed meat, red meat, high-sugar beverages, eggs, potatoes, beer, sweets and
      cakes, snacks and butter, whereas a high adherence to the 'health-conscious'
      pattern represented a high intake of vegetables, vegetable oils, legumes, fruits,
      fish and whole grains. For subjects in the highest compared with those in the
      lowest quintile of the processed foods pattern, the occurrence of abdominal
      obesity was 88 (95 % CI 31, 169) % higher, hypertension was 34 (95 % CI - 4, 86)
      % higher, hypertriacylglycerolaemia was 59 (95 % CI 11, 128 ) % higher and the
      metabolic syndrome was 64 (95 % CI 10, 143) % higher when adjusted for age, sex,
      energy intake, socio-economic status, sport activity and smoking. Furthermore,
      subjects in the highest quintile had statistically significantly higher uric acid
      concentrations and lower folate concentrations (P for trend < 0.05). In contrast,
      subjects in the highest quintile of the health-conscious pattern had a 30 (95 %
      CI 10, 46) % lower occurrence of hypertension, higher folate concentrations and
      lower homocysteine and fibrinogen concentrations (P for trend < 0.05). These data
      strengthen the findings from non-representative studies and emphasise the
      importance of healthy overall food patterns for preventing metabolic
      disturbances.

PMID- 21736840
TI  - Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of
      breast cancer by oestrogen and progesterone receptor status.
AB  - Few studies have evaluated the relationship between the consumption of dietary
      folate and one-carbon metabolism-related nutrients and breast cancer risk defined
      by oestrogen receptor (ER) and progesterone receptor (PR) status. The objective
      of the present study was to examine the associations between dietary folate,
      vitamin B6, vitamin B12, and methionine intake and the risk of breast cancer by
      ER and PR status among Chinese women in Guangdong. A hospital-based case-control
      study was conducted from June 2007 to August 2008, with 438 cases and 438 age (5
      year interval)- and residence (rural/urban)-matched controls. Dietary intake
      information was assessed using a validated FFQ administered through a face-to
      face interview. Unconditional logistic regression models were used to calculate
      multivariate-adjusted OR and 95 % CI. A significant inverse association was found
      between dietary folate and vitamin B6 intake and breast cancer risk. The adjusted
      OR of the highest v. the lowest quartile were 0.32 (95 % CI 0.21, 0.49; P(trend)
      < 0.001) for dietary folate and 0.46 (95 % CI 0.30, 0.69; P(trend) < 0.001) for
      vitamin B6. No associations were observed for vitamin B12 and methionine intake.
      A significant inverse association between dietary folate intake and breast cancer
      risk was observed in all subtypes of ER and PR status. These findings suggest
      that dietary folate and vitamin B6 intakes were inversely associated with breast
      cancer risk. The inverse association did not differ by ER and/or PR status.

PMID- 21736841
TI  - Chloroplast thylakoids reduce glucose uptake and decrease intestinal
      macromolecular permeability.
AB  - Thylakoid membranes, derived from chloroplasts, have previously been shown to
      retard fat digestion and lower blood glucose levels after oral intake. The
      purpose of the present study was to investigate the effect of thylakoid membranes
      on the passage of methyl-glucose, dextran and ovalbumin over rat intestine in
      vitro using Ussing chambers. The results show that thylakoids retard the passage
      of each of the test molecules in a dose-dependent way. The thylakoids appear to
      be attached on the mucosal surface and a mechanism is suggested that the
      thylakoids delay the passage of the test molecules by sterical hindrance. The
      present results indicate that thylakoid membranes may be useful both to control
      intestinal absorption of glucose and to enhance the barrier function of the
      intestine.

PMID- 21736842
TI  - Consistency of children's dietary choices: annual repeat measures from 5 to 13
      years (EarlyBird 49).
AB  - The objective of the present study was to explore the consistency of dietary
      choices made by children as they grow up. The dietary habits of 342 healthy
      children were reported annually from 5 to 13 years on a forty-five-item FFQ and
      analysed by factor analysis. The same two principal dietary patterns--'Healthy'
      and 'Unhealthy'--emerged each year, and their consistency was assessed using
      Tucker's congruence coefficient (phi). Individual dietary z-scores for both of
      these patterns were then calculated every year for each child, and their
      consistency was measured by Pearson's correlation coefficient (r). Linear mixed
      effects modelling was used to investigate individual trends and to quantify
      reliability of the individual dietary z-scores. Dietary patterns were moderately
      consistent and systematic over time (0.65 <= phiHealthy <= 0.76; 0.62 <=
      phiUnhealthy <= 0.78). Individual choices were also consistent year-on-year (0.64
      <= rHealthy <= 0.71; 0.57 <= rUnhealthy <= 0.68). Reliability rose from 70 % with
      a single measure to over 90 % with four consecutive measures. The quality of diet
      diminished over time in 29 % of the children and improved in only 14 %. Dietary
      habits appear to be set early and seldom improve spontaneously.

PMID- 21736843
TI  - Anti-diabetic effect of pyroglutamic acid in type 2 diabetic Goto-Kakizaki rats
      and KK-Ay mice.
AB  - With the rapidly increasing prevalence of type 2 diabetes mellitus (T2DM),
      specific dietary components with anti-diabetic efficacy could be one strategy
      with therapeutic potential. In the present study, the anti-diabetic effects of an
      amino acid, pyroglutamic acid (PA), found in vegetables and fruits were
      investigated in T2DM models using Goto-Kakizaki (GK) rats and KK-Ay mice by
      measuring glucose tolerance and other markers of diabetes. Moreover, the effect
      of PA on gene expression in GK rats was measured by DNA microarray analysis. Oral
      glucose tolerance and serum insulin levels were reduced by PA in both animal
      models. Serum and liver total cholesterol levels were also improved by PA.
      Expression of genes involved with gluconeogenesis and those involved with its
      related transcription factor were down-regulated by feeding PA. In KK-Ay mice,
      the glucokinase:glucose-6-phosphatase (G6Pase) activity ratio increased. From
      these results, it is suggested that dietary PA beneficially modifies glucose and
      lipid metabolism in diabetic animals, and can potentially contribute to the
      mitigation of T2DM.

PMID- 21736844
TI  - Lupin and soya reduce glycaemia acutely in type 2 diabetes.
AB  - Addition of fibre or protein to carbohydrate-rich foods can reduce the glycaemic
      response to those foods. This may assist with glycaemic management in individuals
      with type 2 diabetes. Lupin is a legume rich in fibre and protein. We assessed
      the acute effects of lupin- and soya-based beverages on glucose and insulin
      responses in type 2 diabetic individuals. We hypothesised that the lupin and soya
      beverages would lower the acute glycaemic response compared with a control
      beverage containing no protein or fibre, and that lupin would reduce the
      postprandial glucose more than soya. In a randomised, controlled, cross-over
      trial, twenty-four diabetic adults (nineteen men and five women) attended three
      testing sessions, each 1 week apart. At each session, participants consumed a
      beverage containing 50 g glucose (control), 50 g glucose plus lupin kernel flour
      with 12.5 g fibre and 22 g protein (lupin), or 50 g glucose plus 12.5 g fibre and
      22 g protein from soya isolates (soya). Serum glucose, insulin and C-peptide were
      measured periodically for 4 h following beverage consumption. Compared with the
      control beverage, the 4 h post-beverage glucose response was lower (P < 0.001),
      and the 4 h post-beverage insulin and C-peptide responses were higher (P < 0.001)
      for lupin and soya. Glucose (P = 0.25) and C-peptide (P = 0.07) responses did not
      differ significantly between lupin and soya, but lupin resulted in a lower
      insulin response compared with soya (P = 0.013). Adding lupin or soya to a
      carbohydrate-rich beverage reduces glycaemia acutely in type 2 diabetic
      individuals. This may have a beneficial role in glycaemic management.

PMID- 21736845
TI  - High blood pressure-lowering and vasoprotective effects of milk products in
      experimental hypertension.
AB  - Milk casein-derived angiotensin-converting enzyme (ACE)-inhibitory tripeptides
      isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro)
      have been shown to have antihypertensive effects in human subjects and to
      attenuate the development of hypertension in experimental models. The aim of the
      present study was to investigate the effect of a fermented milk product
      containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols on already established
      hypertension, endothelial dysfunction and aortic gene expression. Male
      spontaneously hypertensive rats (SHR) with baseline systolic blood pressure (SBP)
      of 195 mmHg were given either active milk (tripeptides and plant sterols), milk
      or water ad libitum for 6 weeks. SBP was measured weekly by the tail-cuff method.
      The endothelial function of mesenteric arteries was investigated at the end of
      the study. Aortas were collected for DNA microarray study (Affymetrix Rat Gene
      1.0 ST Array). The main finding was that active milk decreased SBP by 16 mmHg
      compared with water (178 (SEM 3) v. 195 (SEM 3) mmHg; P < 0.001). Milk also had
      an antihypertensive effect. Active milk improved mesenteric artery endothelial
      dysfunction by NO-dependent and endothelium-derived hyperpolarising factor
      dependent mechanisms. Treatment with active milk caused mild changes in aortic
      gene expression; twenty-seven genes were up-regulated and eighty-two down
      regulated. Using the criteria for fold change (fc) < 0.833 or > 1.2 and P < 0.05,
      the most affected (down-regulated) signalling pathways were hedgehog, chemokine
      and leucocyte transendothelial migration pathways. ACE expression was also
      slightly decreased (fc 0.86; P = 0.047). In conclusion, long-term treatment with
      fermented milk enriched with tripeptides and plant sterols decreases SBP,
      improves endothelial dysfunction and affects signalling pathways related to
      inflammatory responses in SHR.

PMID- 21736846
TI  - Intake of alpha-linolenic acid and other fatty acids in relation to the risk of
      bladder cancer: results from the New Hampshire case-control study.
AB  - The role of dietary fat in bladder cancer aetiology is currently unclear due to
      few studies, equivocal findings and a lack of information on important dietary
      fatty acids. The aim of the present study was to investigate the association
      between the intake of major dietary fats and fatty acids and the risk of bladder
      cancer. A case-control study was conducted in New Hampshire, USA. Dietary data
      were collected from 322 cases and 239 controls, and OR and 95 % CI were
      calculated using unconditional logistic regression. Adjustment was made for
      potential confounders: sex, age, smoking status, pack-years smoked, cholesterol
      and energy intake. Statistically significant reduced odds of bladder cancer were
      observed for high intakes (highest quartile v. lowest quartile) of alpha
      linolenic acid (ALA) (OR 0.26, 95 % CI 0.10, 0.65; P for trend = 0.01) and
      vegetable fat (OR 0.39, 95 % CI 0.18, 0.86; P for trend = 0.03). Borderline
      statistically significant reduced odds were detected for polyunsaturated fat (OR
      0.43, 95 % CI 0.19, 0.98; P for trend = 0.07) and linoleic acid (OR 0.43, 95 % CI
      0.19, 0.96; P for trend = 0.06). These fats and fatty acids were highly
      correlated and following adjustment for each other, the only potential inverse
      association to remain was for ALA. The present findings suggest that ALA may have
      a protective role against developing bladder cancer; however, further
      investigation and replication in other epidemiological studies are required.
      Future research should focus on the type, source and quantities of different
      dietary fatty acids consumed.

PMID- 21736847
TI  - Vitamin D, calcium and dairy intake, and risk of oesophageal adenocarcinoma and
      its precursor conditions.
AB  - Evidence is accumulating that vitamin D may be protective against carcinogenesis,
      although exceptions have been observed for some digestive tract neoplasms. The
      aim of the present study was to explore the association between dietary vitamin D
      and related nutrients and the risk of oesophageal adenocarcinoma and its
      precursor conditions, Barrett's oesophagus and reflux oesophagitis. In an all
      Ireland case-control study conducted between March 2002 and July 2005, 218
      oesophageal adenocarcinoma patients, 212 Barrett's oesophagus patients, 208
      reflux oesophagitis patients and 252 population-based controls completed a 101
      item FFQ, and provided lifestyle and demographic information. Multiple logistic
      regression analysis was applied to examine the association between dietary intake
      and disease risk. Oesophageal adenocarcinoma risk was significantly greater for
      individuals with the highest compared with the lowest tertile of vitamin D intake
      (OR 1.99, 95 % CI 1.03, 3.86; P for trend = 0.02). The direct association could
      not be attributed to a particular vitamin D food source. Vitamin D intake was
      unrelated to Barrett's oesophagus and reflux oesophagitis risk. No significant
      associations were observed for Ca or dairy intake and oesophageal adenocarcinoma,
      Barrett's oesophagus or reflux oesophagitis development. High vitamin D intake
      may increase oesophageal adenocarcinoma risk but is not related to reflux
      oesophagitis and Barrett's oesophagus. Ca and dairy product intake did not
      influence the development of these oesophageal lesions. These findings suggest
      that there may be population subgroups at an increased risk of oesophageal
      adenocarcinoma if advice to improve vitamin D intake from foods is implemented.
      Limited work has been conducted in this area, and further research is required.

PMID- 21736848
TI  - Prediction and validation of total and regional fat mass by B-mode ultrasound in
      Japanese pre-pubertal children.
AB  - The present study was performed to develop regression-based prediction equations
      for fat mass by ultrasound in Japanese children and to investigate the validity
      of these equations. A total of 127 healthy Japanese pre-pubertal children aged 6
      12 years were randomly separated into two groups: the model development group
      (fifty-four boys and forty-four girls) and the validation group (eighteen boys
      and eleven girls). Total body, trunk, arm and leg fat masses were initially
      determined by dual-energy X-ray absorptiometry (DXA, Delphi A-QDR whole-body
      scanner; Hologic, Inc., Bedford, MA, USA). Then, fat thickness was measured by B
      mode ultrasound (5 MHz scanning head) at nine sites (arm: lateral forearm,
      anterior and posterior upper arm; trunk: abdomen and subscapular; leg: anterior
      and posterior thigh, anterior and posterior lower leg). Regression analyses were
      used to describe the relationships between the site-matched fat masses (total
      body, arm, trunk and leg) obtained by DXA and ultrasound in the development
      group. When these fat mass prediction equations were applied to the validation
      group, the measured total and regional fat mass was very similar to the predicted
      fat mass (mean difference calculated as predicted - measured fat mass +/- 2 SD;
      total body 0.1 (SD 0.5) kg, arm 0.1 (SD 0.3) kg, trunk - 0.1 (SD 0.3) kg, leg 0.1
      (SD 0.5) kg for boys; total body 0.5 (SD 1.3) kg, arm 0.0 (SD 0.3) kg, trunk 0.1
      (SD 0.8) kg, leg 0.3 (SD 0.6) kg for girls), and the Bland-Altman analysis did
      not indicate a bias. These results suggest that ultrasound-derived prediction
      equations for boys and girls are useful for estimating total and regional fat
      mass.

PMID- 21736849
TI  - The effect of within-meal protein content and taste on subsequent food choice and
      satiety.
AB  - It is posed that protein intake is tightly regulated by the human body. The role
      of sensory qualities in the satiating effects of protein, however, requires
      further clarification. Our objective was to determine the effect of within-meal
      protein content and taste on subsequent food choice and satiety. We used a cross
      over design whereby sixty healthy, unrestrained subjects (twenty-three males and
      thirty-seven females) with a mean age of 20.8 (SD 2.1) years and a mean BMI of
      21.5 (SD 1.6) kg/m2 were offered one of four isoenergetic preloads (rice meal)
      for lunch: two low in protein (about 7 % energy derived from protein) and two
      high in protein (about 25 % energy from protein). Both had a sweet and savoury
      version. At 30 min after preload consumption, subjects were offered an ad libitum
      buffet, consisting of food products differing in protein content (low/high) and
      taste (sweet/savoury). In addition, the computerised Leeds Food Preference
      Questionnaire (LFPQ) was run to assess several components of food reward. The
      results showed no effect of protein content of the preloads on subsequent food
      choice. There was an effect of taste; after eating the savoury preloads, choice
      and intake of sweet products were higher than of savoury products. No such
      preference was seen after the sweet preloads. No differences in satiety were
      observed. To conclude, within one eating episode, within-meal protein content in
      these quantities seems not to have an effect on subsequent food choice. This
      appears to be mostly determined by taste, whereby savoury taste exerts the
      strongest modulating effect. The results of the LFPQ provided insight into
      underlying processes.

PMID- 21736850
TI  - Impact of early malnourishment on the chronic inflammatory response and its
      implications for the effect of indomethacin on Wistar rats.
AB  - The objective of the present study was to investigate whether early
      undernutrition changes the chronic inflammatory response, so as to study its
      influence on pharmacological response to indomethacin. Rat offspring of dams fed
      from the first day of gestation to term or throughout the lactation period
      received a balanced diet (NN) or a basic regional diet (BRD) from northeast
      Brazil. According to their dams, the offspring were divided into three groups:
      NN; basic regional diet during gestation (BRD-g, undernourished during
      gestation); basic regional diet during gestation and lactation (BRD-gl,
      undernourished during gestation and lactation). At 2 months of age, Freund's
      adjuvant (0.2 ml) was inoculated into the plantar surface of the hind paw (day 0)
      of animals. All animals orally received saline (0.9 %) for 28 d. Another group of
      adult offspring was subjected to the same procedure as described above, but
      orally received indomethacin (2 mg/kg) instead of saline, and divided into three
      subgroups: NN treated with indomethacin (NNI); BRD-g treated with indomethacin
      (BRDI-g); BRD-gl treated with indomethacin (BRDI-gl). The hind paw volume was
      calculated on days 0 (initial paw volume), 7, 14 and 28. Hind paw swelling, blood
      albumin and C-reactive protein (CRP) levels and leucocyte counts were evaluated
      as markers of inflammation. Reduced hind paw swelling and the blood levels of
      serum albumin and CRP were found in the BRD-g and BRD-gl offspring. However, no
      difference was found in the leucocyte count. Compared with their respective
      saline-treated groups (NN, BRD-g and BRD-gl), the anti-inflammatory effect of
      indomethacin was lower in the BRDI-g and BRDI-gl groups than in the NNI group. We
      conclude that early undernutrition attenuated the chronic inflammatory response
      and the anti-inflammatory effect of indomethacin.

PMID- 21736851
TI  - Effects of dietary seaweed extract supplementation in sows and post-weaned pigs
      on performance, intestinal morphology, intestinal microflora and immune status.
AB  - The present study investigated the effects of dietary supplementation of a
      seaweed extract (SWE) to sows and weaned pigs on post-weaning growth performance,
      intestinal morphology, intestinal microflora, volatile fatty acid concentrations
      and immune status of pigs at days 11 and 117 post-weaning. Gestating sows (n 20)
      were supplemented with a SWE (0 v. 10.0 g/d) from day 107 of gestation until
      weaning (day 26). At weaning, pigs (four pigs per sow) were divided into two
      groups based on sow diet during lactation and supplemented with a SWE (0 v. 2.8
      g/kg diet), resulting in four treatment groups: (1) BB (basal sows-basal pigs);
      (2) BS (basal sows-treated pigs); (3) SB (treated sows-basal pigs); (4) SS
      (treated sows-treated pigs). Pigs weaned from SWE-supplemented sows had a higher
      average daily gain (ADG) between days 0 and 21 (P < 0.05) post-weaning compared
      with pigs weaned from non-SWE-supplemented sows. Pigs offered post-weaning diets
      (PW) containing SWE had decreased colonic Escherichia coli populations on day 11
      (P < 0.01) and decreased colonic Enterobacteriaceae numbers on day 117 (P <
      0.05). Pigs offered PW containing SWE had a greater mRNA abundance of MUC2 in the
      colon at day 11 post-weaning (P < 0.05) compared with pigs offered unsupplemented
      diets. In conclusion, these results demonstrate that SWE supplementation post
      weaning provides a dietary means to improve gut health and to enhance growth
      performance in starter pigs. Dietary SWE supplementation increased ADG during the
      grower-finisher (GF) phases. However, there was no growth response to SWE
      inclusion in GF diets when pigs were weaned from SWE-supplemented sows.

PMID- 21736852
TI  - Proline betaine and its biotransformation products in fasting urine samples are
      potential biomarkers of habitual citrus fruit consumption.
AB  - The lack of robust measures of dietary exposure hinders a quantitative
      understanding of causal relationships between diet and health. Non-targeted
      metabolite fingerprinting was used to explore the relationships between citrus
      exposure in free-living human subjects, estimated by a FFQ, and the chemical
      content of urine. Volunteers (study 1, n 12; study 2, n 11) were classified into
      high-, medium- and low-frequency citrus consumption groups. Overnight and spot
      fasting urine samples were obtained after exposure to a standardised citrus-free
      evening meal. The urine samples were analysed by flow injection electrospray
      ionisation MS followed by supervised multivariate data classification analysis to
      discover discriminatory features associated with the level of citrus exposure.
      Good separation of high and low citrus consumption classes was achieved. Deeper
      exploration of high-ranked explanatory mass signals revealed several correlated
      signals derived from proline betaine. Targeted analysis of the relative levels of
      proline betaine in both fasting and overnight urine samples demonstrated good
      correlation with FFQ exposure data. Acute exposure of volunteers to orange juice
      resulted in the appearance of proline betaine and several biotransformed products
      in postprandial urine samples. Biomarker validation showed sensitivities of 80.8
      92.2 % and specificities of 74.2-94.1 % (false discovery rate-adjusted P values <
      0.05) for elevated proline betaine in participants who reported high citrus
      consumption. Proline betaine biotransformation products displayed weaker
      quantitative relationships with habitual citrus exposure. Targeted screening for
      the presence of biotransformation products of hesperidin and narirutin, known to
      be abundant in oranges, revealed that they were relatively poor indicators of
      citrus exposure.

PMID- 21736853
TI  - Strawberry anthocyanin and its association with postprandial inflammation and
      insulin.
AB  - The present study investigates the effect of strawberry antioxidants in beverage
      form on meal-induced postprandial inflammatory and insulin responses in human
      subjects. Overweight adults (n 24) consumed a high-carbohydrate, moderate-fat
      meal (HCFM) accompanied by either a strawberry or a placebo beverage in a cross
      over design. Postprandial changes in plasma anthocyanins, their metabolites,
      insulin, glucose and inflammatory markers were assessed for 6 h. The postprandial
      concentrations of pelargonidin sulfate and pelargonidin-3-O-glucoside were
      significantly increased when the strawberry beverage was consumed concurrently
      with the HCFM compared with the placebo beverage (P < 0.001). The strawberry
      beverage significantly attenuated the postprandial inflammatory response as
      measured by high-sensitivity C-reactive protein and IL-6 (P < 0.05) induced by
      the HCFM. It was also associated with a reduction in postprandial insulin
      response (P < 0.05). Collectively, these data provide evidence for favourable
      effects of strawberry antioxidants on postprandial inflammation and insulin
      sensitivity.

PMID- 21736854
TI  - Occurrence of certain cuticular structures confirms functionality of dorsal
      abdominal scent glands in Acanthosomatidae (Heteroptera: Pentatomoidea).
AB  - Elasmucha ferrugata (Fabricius, 1787) (Heteroptera: Acanthosomatidae) provides
      maternal care of eggs and larvae. Adults of both sexes have functional anterior
      dorsal abdominal scent glands (DAGs). Study of all internal and external
      cuticular structures of DAGs revealed that no DAGs are fully functional in the
      1st larval instar, and very probably they are only slightly functional in the 2nd
      instar. Median and posterior DAGs are undoubtedly not functional in adults. There
      exists sexual dimorphism in the number of multicellular glandular units in
      anterior glands in adults. The occurrence of cuticular ductules of these units
      proves these to be functional glands. This is best considered in combination with
      the findings of a well-developed evaporatorium. Developed cuticular intima of the
      gland reservoir and/or the nearly closed ostiole or ostiolar scar bears no
      information about the functionality of the gland.

PMID- 21736855
TI  - A karyological study of the genus Pnigalio Schrank (Hymenoptera: Eulophidae):
      assessing the taxonomic utility of chromosomes at the species level.
AB  - We provide a karyological study of 12 species of the genus Pnigalio in an attempt
      to evaluate the taxonomic utility of karyotypes at the species level. For all
      species of Pnigalio examined the number of chromosome was 2n=12. Karyotype
      formulae presented mainly metacentric and submetacentric chromosomes, although a
      pair of acrocentrics or subtelocentrics, shorter than biarmed chromosomes, was
      present in some species. The analysis of karyotypes of Pnigalio showed frequent
      but not general interspecific variability of the chromosome traits. Although most
      of the studied species revealed concordance between morphological and
      karyological characters (centromeric index and relative length), two other
      categories have been identified: morphologically distinct species without
      reciprocal differences in karyotype structure, and morphologically similar
      species that strongly differ in chromosomal characters.

PMID- 21736856
TI  - Is microanalysis possible in the helium ion microscope?
AB  - Because the ability to perform some form of chemical microanalysis has become an
      essential feature for any microscope, it is necessary to investigate what options
      are available in the new "ORION" helium ion microscope (HIM). The HIM has the
      ability to visualize local variations in specimen chemistry in both the ion
      induced secondary electron and the Rutherford backscattered imaging modes, but
      this provides only limited and qualitative information. Quantitative, elementally
      specific, microanalysis could be performed in the HIM using secondary electron
      spectroscopy, Rutherford backscattered ion spectroscopy, or secondary ion mass
      spectroscopy, but while each of these options has promise, none of them can
      presently guarantee either reliable element identification or quantitative
      analysis across the periodic table.

PMID- 21736857
TI  - Cost-effectiveness of etanercept treatment in early active rheumatoid arthritis
      followed by dose adjustment.
AB  - OBJECTIVES: To explore the cost-effectiveness of early biologic treatment,
      followed by dose-reduction in the case of remission, of active rheumatoid
      arthritis (RA), compared with standard treatment with methotrexate (MTX) in
      Sweden. METHODS: Effectiveness (function, disease activity, erosions) in early RA
      for both alternatives was taken from a clinical trial comparing etanercept (ETA)
      combined with MTX to MTX alone. Patients discontinuing treatment can switch to
      another or their first biologic treatment. For patients in remission (Disease
      Activity Score [DAS28] < 2.6), ETA is reduced to half the dose. Return to full
      dose occurs when DAS28 reaches >= 3.2 again. Costs and utilities by level of
      functional capacity from an observational study are used. The model is analyzed
      as a micro-simulation and results are presented from the societal perspective for
      Sweden, for 10 years; costs (?2008) and effects are discounted at 3 percent.
      Sensitivity analysis was performed for the perspective, the time horizon,
      switching, and dose-reduction. RESULTS: The main analysis conservatively assumes
      50 percent switching at discontinuation. The cost per quality-adjusted life-year
      (QALY) gained with early ETA/MTX treatment is ?13,500 (societal perspective,
      incremental cost of ?15,500 and incremental QALYs of 1.15). With 75 percent
      switching, the cost per QALY gained was ?10,400. Over 20 years, the cost per QALY
      gained was ?8,200. Results were further sensitive to the time patients remained
      on half dose and the perspective. CONCLUSIONS AND POLICY IMPLICATIONS: This study
      combines clinical trial and clinical practice data to explore cost-effective
      treatment scenarios in early RA, including the use of biologics. Our results
      indicate that a situation where a considerable proportion of patients achieve
      remission, dose-adjustments will increase the cost-effectiveness of treatment.

PMID- 21736858
TI  - Multi-source synthesis of data to inform health policy.
AB  - OBJECTIVES: To propose a new method for comparing and integrating original
      qualitative data with systematic reviews of quantitative and qualitative studies,
      demonstrated by a study of the psychosocial needs of chronic fatigue syndrome
      (CFS) sufferers in Quebec. METHODS: A systematic literature review was performed
      across various databases for English and French language studies, on the
      psychosocial aspects of CFS. Qualitative, quantitative, and mixed method studies
      published between January 1994 and July 2008 were included. Unpublished
      literature and reference lists of included studies were also searched. Themes
      identified in the literature were used to guide semi-structured interviews with
      seventeen CFS-sufferers, mostly recruited from a large specialist practice in
      Montreal. Interviews were transcribed verbatim and validated by a research
      assistant. Transcripts were coded using the identified themes. New codes were
      created when new issues arose. All themes were subsequently synthesized into
      overall categories using a constant comparative method. RESULTS: The literature
      search yielded thirty-one papers: twenty-eight primary studies and three
      systematic reviews. Twelve themes were identified and synthesized into four
      overall problem categories, such as "Lack of professional recognition."
      Interviews confirmed findings from the literature, but also revealed unidentified
      needs specific to CFS-sufferers in Quebec. Policy recommendations were provided
      to address these needs. CONCLUSIONS: Multi-Source Synthesis provides a systematic
      method for synthesizing data from original studies with literature findings,
      thereby broadening the knowledge base and the local relevance of decisions
      concerning specific patient populations.

PMID- 21736859
TI  - Methylphenidate delivery mechanisms for the treatment of children with attention
      deficit hyperactivity disorder: heterogeneity in parent preferences.
AB  - OBJECTIVES: Extended-release therapies avoid the need for children with attention
      deficit/hyperactivity disorder (ADHD) to take medication at school. Recently a
      transdermal delivery system has been developed which can allow symptom control
      all day long but with greater dosing flexibility. This study explored the
      parents' preferences regarding oral and transdermal therapy. METHODS: A
      nonsystematic and qualitative literature review and in-depth interviews with
      parents and physicians helped identify salient treatment attributes for a
      discrete choice experiment. Treatment attributes included mode of administration
      (tablet or transdermal), speed of onset (30-90 min); duration (lasts until 3-9
      pm) and ability to tailor the drug to different needs (no flexibility, limited
      flexibility, easy to adjust to different days). A convenience sample of parents
      of children treated for ADHD (n = 200) were recruited using a recruitment agency.
      Data were analyzed using generalized estimating equations (GEE). RESULTS:
      Parents' preferred once-a-day oral therapy (odds ratio [OR] = 1.76 [95 percent
      confidence interval {CI}, 1.43 - 2.18]); rapid speed of onset (OR = 1.22 [95
      percent CI, 1.07 - 1.39]), and symptom control until 9 pm (OR = 3.79 [95 percent
      CI, 2.98 - 4.82]). Analyses identified that 30 percent of parents preferred
      transdermal treatment and this subgroup preferred treatments with a fast onset of
      action. CONCLUSIONS: This survey demonstrates that parents of ADHD children have
      different preferences for the ADHD treatments prescribed for their children. A
      distinct subgroup of parents prefer the transdermal therapy. These parents were
      less likely to be working and so monitoring compliance and doing after school
      activities may have been easier.

PMID- 21736860
TI  - Tackling ethical issues in health technology assessment: a proposed framework.
AB  - OBJECTIVES: Values are intrinsic to the use of health technology assessments
      (HTAs) in health policy, but neglecting value assumptions in HTA makes their
      results appear more robust or normatively neutral than may be the case. Results
      of a 2003 survey by the International Network of Agencies for Health Technology
      Assessment (INAHTA) revealed the existence of disparate methods for making values
      and ethical issues explicit when conducting HTA. METHODS: An Ethics Working
      Group, with representation from sixteen agencies, was established to develop a
      framework for addressing ethical issues in HTA. Using an iterative approach, with
      email exchanges and face-to-face workshops, a report on Handling Ethical Issues
      was produced. RESULTS: This study describes the development process and the
      agreed upon framework for reflexive ethical analysis that aims to uncover and
      explore the ethical implications of technologies through an integrated, context
      sensitive approach and situates the proposed framework within previous work in
      the development of ethics analysis in HTA. CONCLUSIONS: It is important that
      methodological approaches to address ethical reflection in HTA be integrative and
      context sensitive. The question-based approach described and recommended here is
      meant to elicit this type of reflection in a way that can be used by HTA
      agencies. The questions proposed are considered only as a starting point for
      handling ethics issues, but their use would represent a significant improvement
      over much of the existing practice.

PMID- 21736861
TI  - Understanding the dermal light sense in the context of integrative photoreceptor
      cell biology.
AB  - While the concept of a dermal light sense has existed for over a century, little
      progress has been made in our understanding of the mechanisms underlying
      dispersed photoreception and the evolutionary histories of dispersed
      photoreceptor cells. These cells historically have been difficult to locate and
      positively identify, but modern molecular techniques, integrated with existing
      behavioral, morphological, and physiological data, will make cell identification
      easier and allow us to address questions of mechanism and evolution. With this in
      mind, we propose a new classification scheme for all photoreceptor cell types
      based on two axes, cell distribution (aggregated vs. dispersed) and position
      within neural networks (first order vs. high order). All photoreceptor cells fall
      within one of four quadrants created by these axes: aggregated/high order,
      dispersed/high order, aggregated/first order, or dispersed/first order. This new
      method of organization will help researchers make objective comparisons between
      different photoreceptor cell types. Using integrative data from four major phyla
      (Mollusca, Cnidaria, Echinodermata, and Arthropoda), we also provide evidence for
      three hypotheses for dispersed photoreceptor cell function and evolution. First,
      aside from echinoderms, we find that animals often use dispersed photoreceptor
      cells for tasks that do not require spatial vision. Second, although there are
      both echinoderm and arthropod exceptions, we find that dispersed photoreceptor
      cells generally lack morphological specializations that either enhance light
      gathering or aid in the collection of directional information about light. Third,
      we find that dispersed photoreceptor cells have evolved a number of times in
      Metazoa and that most dispersed photoreceptor cells have likely evolved through
      the co-option of existing phototransduction cascades. Our new classification
      scheme, combined with modern investigative techniques, will help us address these
      hypotheses in great detail and generate new hypothesis regarding the function and
      evolution of dispersed photoreceptor cells.

PMID- 21736862
TI  - Inlay-retained zirconia fixed dental prostheses: modified designs for a
      completely adhesive approach.
AB  - Currently, there are many options for single-tooth replacement: metal-ceramic,
      all-ceramic, direct or indirect fibre-reinforced composite fixed dental
      prostheses (FDPs) or implants. Inlay-retained FDPs may especially be indicated
      when adjacent teeth have been previously restored and when implant placement is
      not possible or not indicated. In such cases, both metal-ceramic and fibre
      reinforced composite FDPs have certain disadvantages. In this paper, we describe
      the use of all-ceramic inlay-retained FDPs with zirconia frameworks, veneered
      using a press-on technique.

PMID- 21736863
TI  - Treatment of a large maxillary cyst with marsupialization, decompression,
      surgical endodontic therapy and enucleation.
AB  - A large maxillary cyst was treated for 3 months with marsupialization and
      decompression, followed by surgical endodontic therapy of the affected teeth and
      cystectomy. Although small cystic lesions will typically heal with nonsurgical
      endodontic therapy, larger lesions may need additional treatment. Surgical
      enucleation of a large cystic lesion may lead to damage of other teeth or
      anatomic structures. Therefore, treatment should begin with the more conservative
      approach of decompression, to reduce the size of the lesion, followed by
      apicoectomy and cystectomy.

PMID- 21736864
TI  - Fracture resistance of 3 types of primary esthetic stainless steel crowns.
AB  - BACKGROUND AND OBJECTIVE: Demand is increasing for esthetic restorations in
      pediatric dentistry. When full coverage is indicated, one option is to use
      esthetic stainless steel crowns (SSCs). However, this type of crown is prone to
      fracture. The purpose of this study was to evaluate the fracture resistance of 3
      types of esthetic SSCs. MATERIALS AND METHODS: Esthetic SSCs for first primary
      mandibular molars were cemented to idealized epoxy dies with glass ionomer
      cement. The die-crown units were fractured on a universal testing machine. The
      force was delivered by a stainless steel ball fixture, set in a uniaxial lever to
      replicate a cusp contact, with a crosshead speed of 1 mm/min. The differences
      among the 3 types of crown, in terms of force required to fracture, were compared
      statistically by 1-way analysis of variance. Pairwise comparisons were performed
      with Fisher's protected least significant difference test, at an overall
      significance level of 5%. RESULTS: The force required to fracture, expressed as
      average +/- standard error, did not differ significantly among the 3 brands of
      esthetic SSCs: 1730 N +/- 50 N, 1826 N +/- 62 N and 1671 N +/- 68 N, respectively
      (p = 0.19), well below the maximum bite force of pediatric patients determined in
      a previous study. CONCLUSION: Esthetic SSCs should be able to resist occlusal
      forces over short clinical periods. However, long-term occlusal loading and
      fatigue failures should be taken into account when evaluating the success of this
      type of crown.

PMID- 21736865
TI  - Voices from the storm: a critical review of quantitative studies of auditory
      verbal hallucinations and childhood sexual abuse.
AB  - Although an association between hallucinations and sexual abuse has been
      documented, the relation between specifically auditory verbal hallucinations
      (AVHs) and childhood sexual abuse (CSA) is less clear. This study reviewed
      quantitative studies of AVHs and CSA. 36% of psychiatric patients with AVHs, and
      22% of non-psychiatric patients with AVHs, reported CSA. At least 16% of the
      general population with auditory hallucinations also reported CSA. The majority
      of studies reviewed found that those with AVHs were more likely to be survivors
      of CSA than individuals without AVHs. 56% of psychiatric patients with CSA
      reported AVHs, and at least 21% of the general population with CSA reported
      auditory hallucinations. A majority of studies found survivors of CSA were more
      likely to report AVHs than individuals without CSA. Ability to impute a causal
      role for CSA was impaired by such studies' failures to control for potentially
      confounding variables. Yet, studies of AVH content showed links between the
      content of voices and the content of CSA in some voice-hearers. It is concluded
      that although a clear association between CSA and AVHs exists, there is not yet
      reliable quantitative evidence of a causal relation. Implications for mental
      health professionals and for future research, are discussed.

PMID- 21736866
TI  - Projected thickness reconstruction from a single defocused transmission electron
      microscope image of an amorphous object.
AB  - Single defocused transmission electron microscope phase contrast images are used
      to reconstruct the projected thickness map of a single-material object. The
      algorithm is non-iterative and stable, and we extend it to account for the
      presence of spherical aberration in the objective optics. The technique can
      reconstruct the projected thickness map of general single-material objects in the
      strong phase/weak amplitude regime. It is sensitive to any excursions in the
      projected thickness from the average, and ideal for examining voids and free
      volume accumulation in amorphous/glassy materials at the nanometer scale. The
      resolution of the technique depends on the choice of defocus and the thickness of
      the specimen. In a certain regime, we demonstrate that variations in the
      transverse projected thickness with a lateral diameter of ~ 0.25 nm may be
      detected. We use our algorithm to quantitatively reconstruct the projected
      thickness of latex sphere test specimens from single defocused electron
      micrographs. We demonstrate that the reconstruction has a large tolerance for
      error in the input parameters. Simulations confirm that the technique is
      quantitative, and demonstrate that the origin of low-frequency artifacts is an
      instability due to noise. We show that the autocorrelation of the projected
      thickness map may be used to measure the size of open structures in the object
      using both simulation and latex sphere data.

PMID- 21736867
TI  - Idiotype immunization following high-dose therapy and autologous stem cell
      transplantation for non-Hodgkin lymphoma.
AB  - The treatment of low- and intermediate-grade subtypes of malignant lymphoma
      continues to evolve. Mantle cell lymphoma (MCL) accounts for 6% of all non
      Hodgkin lymphoma (NHL) and is generally considered incurable. Although high
      response rates can be achieved with initial chemotherapy, median survival is only
      3-4 years. Intensified consolidation with high-dose therapy (HDT) and autologous
      stem cell transplantation (ASCT) has been reported to improve progression-free
      survival (PFS), but most patients eventually relapse. Indolent lymphoma accounts
      for 35% of all NHL and is associated with a median survival of 9 years. Similar
      to MCL, it is also generally considered incurable, and the PFS also appears to be
      improved following HDT/ASCT. We initiated a pilot study to evaluate idiotype (Id)
      vaccination following HDT and ASCT for patients with MCL, indolent, and
      transformed NHL to evaluate the ability of Id-keyhole limpet hemocyanin (KLH) to
      induce immune responses, and to evaluate overall survival (OS) and PFS. We
      treated 15 patients: 8 with MCL, 4 with follicular lymphoma, 1 with small
      lymphocytic lymphoma, and 2 with transformed lymphoma. After a median follow-up
      of approximately 6.3 years (range: 1-9), PFS and OS at 9.05 years from time of
      ASCT are 59% and 52%, respectively.

PMID- 21736868
TI  - Steroid-refractory acute GVHD: lack of long-term improved survival using new
      generation anticytokine treatment.
AB  - There is no consensus on the optimal treatment of steroid-refractory acute graft
      versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell
      transplantation. In our center, the treatment policy has changed over time with
      mycophenolate mofetil (MMF) being used from 1999 to 2003, and etanercept or
      inolimomab after 2004. An observational study compared survival and infection
      rates in all consecutive patients receiving 1 of these 3 treatments. Ninety-three
      patients were included. The main end point was overall survival (OS). Median age
      was 37 years. Acute GVHD developed at a median of 15 days after transplantation.
      Second-line treatment was initiated a median of 12 days after aGVHD diagnosis.
      Therapies were MMF in 56%, inolimomab in 22%, and etanercept in 23% of the
      patients. Overall, second-line treatment response rate was 45% (complete
      response: 28%), MMF: 55%, inolimomab: 35%, and etanercept: 28%. With 74 months
      median follow-up, the 2-year survival was 30% (95% confidence interval: 22-41).
      Risk factors significantly associated with OS in multivariate analysis were
      disease status at transplantation; grade III-IV aGVHD at second-line treatment
      institution; and liver involvement. None of the second-line therapy influenced
      this poor outcome. Viral and fungal infections were not statistically different
      among the 3 treatment options; however, bacterial infections were more frequent
      in patients treated with anticytokines. Over an 11-year period, 3 treatment
      strategies, including 2 anticytokines, give similar results in patients with SR
      aGVHD.

PMID- 21736869
TI  - Accurate targeting of daily intravenous busulfan with 8-hour blood sampling in
      hospitalized adult hematopoietic cell transplant recipients.
AB  - Daily intravenous (i.v.) busulfan is increasingly being used in hematopoietic
      cell transplantation (HCT) conditioning regimens. Intravenous busulfan doses
      administered at the traditional frequency of every 6 hours can be targeted
      ((T)Bu) to a patient-specific concentration at steady state (C(ss)) using
      therapeutic drug monitoring (TDM). In this report, we describe our experiences
      with TDM of daily i.v. busulfan in an adult population, with the specific aims of
      (1) evaluating covariates associated with busulfan clearance, and (2) assessing
      the feasibility of TDM for outpatient administration of daily (T)Bu with
      pharmacokinetic sampling over 6 hours. A retrospective pharmacokinetic analysis
      was conducted in 87 adults receiving daily (T)Bu as part of cyclophosphamide
      followed by (T)BU (CY/(T)BU), fludarabine monophosphate (fludarabine) followed by
      (T)BU, or (T)BU concurrent with fludarabine conditioning. The desired C(ss) was
      achieved in 85% of patients receiving daily i.v. busulfan. Busulfan clearance was
      not associated with sex or age, but was associated with the day of dosing and
      conditioning regimen (P = .0016). In patients receiving CY/(T)BU, no differences
      in clearance were found between dosing days (P > .36); however, clearance
      decreased significantly in patients receiving fludarabine-based regimens (P =
      .0016). Busulfan clearance and C(ss) estimates from pharmacokinetic sampling over
      8, 11, or 24 hours were comparable (P > .4). However, pharmacokinetic modeling of
      individual patient concentration-time data over 6 hours could not reliably
      estimate busulfan clearance or C(ss).

PMID- 21736870
TI  - Protein kinase Cdelta mediates the activation of protein kinase D2 in platelets.
AB  - Protein kinase D (PKD) is a subfamily of serine/threonine specific family of
      kinases, comprised of PKD1, PKD2 and PKD3 (PKCMU, PKD2 and PKCv in humans). It is
      known that PKCs activate PKD, but the relative expression of isoforms of PKD or
      the specific PKC isoform/s responsible for its activation in platelets is not
      known. This study is aimed at investigating the pathway involved in activation of
      PKD in platelets. We show that PKD2 is the major isoform of PKD that is expressed
      in human as well as murine platelets but not PKD1 or PKD3. PKD2 activation
      induced by AYPGKF was abolished with a G(q) inhibitor YM-254890, but was not
      affected by Y-27632, a RhoA/p160ROCK inhibitor, indicating that PKD2 activation
      is G(q)-, but not G12/13-mediated Rho-kinase dependent. Calcium-mediated signals
      are also required for activation of PKD2 as dimethyl BAPTA inhibited its
      phosphorylation. GF109203X, a pan PKC inhibitor abolished PKD2 phosphorylation
      but Go6976, a classical PKC inhibitor had no effect suggesting that novel PKC
      isoforms are involved in PKD2 activation. Importantly, Rottlerin, a non-selective
      PKCdelta inhibitor, inhibited AYPGKF-induced PKD2 activation in human platelets.
      Similarly, AYPGKF- and Convulxin-induced PKD2 phosphorylation was dramatically
      inhibited in PKCdelta-deficient platelets, but not in PKCtheta- or PKCE-deficient
      murine platelets compared to that of wild type platelets. Hence, we conclude that
      PKD2 is a common signaling target downstream of various agonist receptors in
      platelets and G(q)-mediated signals along with calcium and novel PKC isoforms, in
      particular, PKCdelta activate PKD2 in platelets.

PMID- 21736871
TI  - Progress and challenges in the study of alpha6-containing nicotinic acetylcholine
      receptors.
AB  - Recent progress has been made in the understanding of the anatomical
      distribution, composition, and physiological role of nicotinic acetylcholine
      receptors containing the alpha6 subunit. Extensive study by many researchers has
      indicated that a collection of alpha6-containing receptors representing a
      nicotinic sub-family is relevant in preclinical models of nicotine self
      administration and locomotor activity. Due to a number of technical difficulties,
      the state of the art of in vitro model systems expressing alpha6-containing
      receptors has lagged behind the state of knowledge of native alpha6 nAChR subunit
      composition. Several techniques, such as the expression of chimeric and
      concatameric alpha6 subunit constructs in oocytes and mammalian cell lines have
      been employed to overcome these obstacles. There remains a need for other
      critical tools, such as selective small molecules and radioligands, to advance
      the field of research and to allow the discovery and development of potential
      therapeutics targeting alpha6-containing receptors for smoking cessation,
      Parkinson's disease and other disorders.

PMID- 21736872
TI  - Stimulation of gastric ulcer healing by heat shock protein 70.
AB  - It is important in treatment of gastric ulcers to not only prevent further ulcer
      formation but also enhance ulcer healing. When cells are exposed to gastric
      irritants, expression of heat shock proteins (HSPs) is induced, making the cells
      resistant to the irritants. We recently reported direct evidence that HSPs,
      especially HSP70, are preventive against irritant-induced gastric ulcer
      formation. Gastric ulcer healing is a process involving cell proliferation and
      migration at the gastric ulcer margin and angiogenesis in granulation tissue. In
      this study, we have examined the role of HSP70 in gastric ulcer healing. Gastric
      ulcers were produced by focal and serosal application of acetic acid. Expression
      of HSP70 was induced in both the gastric ulcer margin and granulation tissue.
      Compared with wild-type mice, gastric ulcer healing was accelerated in transgenic
      mice expressing HSP70, and both cell proliferation at the gastric ulcer margin
      and angiogenesis in granulation tissue were enhanced. Oral administration of
      geranylgeranylacetone, an inducer of HSPs, to wild-type mice, either prior to or
      after ulcer formation, not only induced expression of HSP70 in the stomach but
      also accelerated gastric ulcer healing. On the other hand, oral administration of
      purified recombinant HSP70 prior to the ulcer formation, but not after formation,
      stimulated gastric ulcer healing. This study provides the first evidence that
      HSP70 accelerates gastric ulcer healing. The results also suggest that both the
      HSP70 produced prior to ulcer formation and released from damaged cells, and the
      HSP70 produced after ulcer formation are involved in this accelerated healing
      process.

PMID- 21736873
TI  - Novel proteasome-inhibitory syrbactin analogs inducing endoplasmic reticulum
      stress and apoptosis in hematological tumor cell lines.
AB  - The proteasome has been recognized as a druggable target in cancer cells, and
      this has led to searches for pharmacologic agents that target this cellular
      organelle for cancer therapeutic purposes. Syrbactins are a group of microbial
      metabolites consisting of two related families, the glidobactins and the
      syringolins. Some members of this group have revealed cytotoxic efficacy in tumor
      cells, and more recently it was discovered that they exert proteasome-inhibitory
      function. Based on this therapeutic promise and to gain further understanding of
      their molecular modes of action, we chemically synthesized de-novo three novel
      syrbactin analogs and characterized their proteasome-inhibitory and in vitro anti
      neoplastic activity in human cell lines representing multiple myeloma,
      Waldenstrom's macroglobulinemia, and lymphocytic leukemia. Our results show that
      two of these novel compounds are able to inhibit proteasome activity in the
      nanomolar range, reduce the expression of anti-apoptotic proteins survivin and
      Mcl-1, and cause severe endoplasmic reticulum (ER) stress, resulting in
      pronounced tumor cell death. These anticancer effects can be synergistically
      enhanced when the agents are combined with thapsigargin, which further aggravates
      ER stress by a different mechanism. Taken together, our findings support the
      notion that syrbactin analogs may provide a structural platform for the
      development of novel cancer therapeutics, and that their efficacy may be further
      increased when complemented with other agents that trigger ER stress.

PMID- 21736874
TI  - Amelioration of glucose induced hemolysis of human erythrocytes by vitamin E.
AB  - Cells under aerobic condition are always threatened with the insult of reactive
      oxygen species, which are efficiently taken care of by the highly powerful
      antioxidant systems of the cell. The erythrocytes (RBCs) are constantly exposed
      to oxygen and oxidative stress but their metabolic activity is capable of
      reversing the injury under normal conditions. In vitro hemolysis of RBCs induced
      by 5, 10 and 20mM glucose was used as a model to study the free radical induced
      damage of biological membranes in hyperglycemic conditions and the protection
      rendered by vitamin E on the same. RBCs are susceptible to oxidative damage,
      peroxidation of the membrane lipids, release of hemoglobin (hemolysis) and
      alteration in activity of antioxidant enzymes catalase and superoxide dismutase.
      The glucose induced oxidative stress and the protective effect of vitamin E on
      cellular membrane of human RBCs manifested as inhibition of membrane peroxidation
      and protein oxidation and restoration of activities of superoxide dismutase and
      catalase, was investigated. Thiobarbituric acid reactive substances are generated
      from decomposition of lipid peroxides and their determination gives a reliable
      estimate of the amount of lipid peroxides present in the membrane. Vitamin E at
      18 MUg/ml (normal serum level) strongly enhanced the RBC resistance to oxidative
      lysis leading to only 50-55% hemolysis in 24h, whereas RBCs treated with 10 and
      20mM glucose without vitamin E leads to 70-80% hemolysis in 24h. Levels of
      enzymic antioxidants catalase, superoxide dismutase and nonenzymic antioxidants
      glutathione showed restoration to normal levels in presence of vitamin E. The
      study shows that vitamin E can protect the erythrocyte membrane exposed to
      hyperglycemic conditions and so a superior antioxidant status of a diabetic
      patient may be helpful in retarding the progressive tissue damage seen in chronic
      diabetic patients.

PMID- 21736875
TI  - Salivary cytokines in cell proliferation and cancer.
AB  - While the presence of multiple systemic steroids, amines and peptides in saliva
      has been reported, other hormones of the circulation do not appear in saliva.
      Substances present within saliva may be classified in different groups: first,
      those which passively display blood plasma concentrations and constitute a
      promising alternative to evaluate certain systemic parameters. Second, molecules
      which seem to play a more active, regulatory role within the upper
      gastrointestinal tract. Concerning the latter, a growing awareness, especially
      with regards to salivary peptides has been established. Up to now, understanding
      the distinct effects of salivary peptides known so far is in its infancy. Various
      publications, however, emphasize important effects of their presence. Salivary
      peptides can influence inflammatory processes and cell proliferation in epithelia
      of the upper digestive tract. These include transforming growth factors (TGFs),
      epidermal growth factors (EGFs), vascular endothelial growth factors (VEGFs) as
      well as amines such as melatonin. Of those, candidate cytokines like interleukin
      8, tumor necrosis factors (TNFs) and leptin are involved in neoplastic activities
      of salivary glands and the oral cavity. The exact mechanisms of action are not
      yet completely understood, but their presence can be utilized for diagnostic
      purposes. Salivary gland tumors in patients may, in certain circumstances, be
      identified by saliva diagnostics. Saliva samples of the concerned patients, for
      instance, reveal significantly higher leptin concentrations than those of healthy
      individuals. Numerous studies postulate that, beside single indicators, the
      establishment of salivary hormone profiles may assist clinicians and researchers
      in detecting tumors and other pathologies of the oral cavity, including adjacent
      tissues, with high sensitivity and specificity.

PMID- 21736876
TI  - Phosphorylated beta-catenin localizes to centrosomes of neuronal progenitors and
      is required for cell polarity and neurogenesis in developing midbrain.
AB  - beta-catenin has well-established functions in cell growth and differentiation as
      part of the Wnt signaling pathway and in regulation of cellular adhesion with E
      cadherin. Here we studied its significance in midbrain development by temporally
      controlled deletion of beta-catenin allowing simultaneous analysis of complete
      (beta-cat-null) and partial (beta-cat-low) loss-of-function phenotypes in
      progenitor cells. beta-cat-null cells did not contain centrosomes or a
      microtubule network and were unpolarized forming delaminated bulges. beta-cat-low
      cells displayed defects in the orientation of the mitotic spindle, increased
      asymmetric cell divisions and premature differentiation in absence of alterations
      in polarity or adhesion. The spindle defect was associated with decreased
      centrosomal S33/S34/T41 phosphorylated beta-catenin (p-beta-cat) and centrosomal
      and microtubule defects. Interestingly, neural progenitor cells in mice
      expressing only unphosphorylatable beta-catenin share several phenotypes with
      beta-catenin loss-of-function mice with defects in microtubules and polarity. The
      results demonstrate a novel function for p-beta-cat in maintaining
      neuroepithelial integrity and suggest that centrosomal p-beta-cat is required to
      maintain symmetric cleavages and polarity in neural progenitors.

PMID- 21736877
TI  - Focus on molecules: Norrin.

PMID- 21736878
TI  - Return of bradykinesia after subthalamic stimulation ceases: relationship to
      electrode location.
AB  - In 20 subjects we quantified the rate at which subthalamic nucleus deep brain
      stimulation effects on Parkinson's bradykinesia "washed-out" after stimulation
      ceased. We found that wash-out was a two-step process, consisting of an initial
      fast decrease in stimulation's therapeutic effect, followed by a further, slow
      decline. Moreover, the relative contribution of the fast and slow components
      differed between patients. Finally, we found that lateral stimulation caused more
      of the fast-decaying component, while medial stimulation caused more of the slow
      decaying component. This implies the existence of at least two separate
      mechanisms by which subthalamic nucleus deep brain stimulation improves
      bradykinesia, associated with activation of spatially separate zones in the
      vicinity of the subthalamic nucleus.

PMID- 21736879
TI  - Human microRNA target identification by RRSM.
AB  - MicroRNAs (miRNAs) are small endogenously expressed non-coding RNAs that regulate
      target messenger RNAs in various biological processes. In recent years, there
      have been many studies concentrated on the discovery of new miRNAs and
      identification of their mRNA targets. Although researchers have identified many
      miRNAs, few miRNA targets have been identified by actual experimental methods. To
      expedite the identification of miRNA targets for experimental verification, in
      the literature approaches based on the sequence or microarray expression analysis
      have been established to discover the potential miRNA targets. In this study, we
      focus on the human miRNA target prediction and propose a generalized relative R2
      method (RRSM) to find many high-confidence targets. Many targets have been
      confirmed from previous studies. The targets for several miRNAs discovered by the
      HITS-CLIP method in a recent study have also been selected by our study.

PMID- 21736880
TI  - Characterization of novel checkpoint kinase 1 inhibitors by in vitro assays and
      in human cancer cells treated with topoisomerase inhibitors.
AB  - AIMS: We have developed biochemical and cell based assays to characterize small
      therapeutic molecules that inhibit the DNA damage checkpoint enzyme, Chk1
      (Checkpoint kinase 1). MAIN METHODS: To prepare a screen of large chemical
      libraries, we purified the full-length and the catalytic domain versions of human
      Chk1. We characterized their properties and then selected full-length Chk1 as the
      variant most suitable for screening. We then identified and characterized
      structurally different Chk1 inhibitors in cell based-assays by measuring
      cytotoxicity and checkpoint bypass activity. KEY FINDINGS: We treated human cells
      with topoisomerase I inhibitors and demonstrated that at the time of Chk1
      inhibitor addition, the cells have damaged DNA and activated Chk1. One Chk1
      inhibitor, the indolocarbazole S27888, was active in the checkpoint bypass assay.
      SIGNIFICANCE: Knowing that the protein kinase inhibitory properties are different
      for each inhibitor, it seems that only a limited range of inhibitory activity is
      tolerated by cells. Chk1 has an essential role in determining how cancer cells
      respond to genotoxic treatments, therefore, inhibitors of this protein kinase are
      of great medical interest.

PMID- 21736881
TI  - Estimating mutation rates in low-replication experiments.
AB  - Since mutation rate is a key biological parameter, its proper estimation has
      received great attention for decades. However, instead of the mutation rate, many
      authors opt for reporting the average mutant frequency, a less meaningful
      quantity. This is because the standard methods to estimate the mutation rate,
      derived from the Luria and Delbruck's fluctuation analysis, ideally require high
      replication experiments to be applied; a requirement often unattainable due to
      constraints of time, budget or sample availability. But the main problem with
      mutant frequency, apart from being less informative, is its poor reproducibility;
      an especially marked defect when the chosen average is the arithmetic mean.
      Several authors tried to avoid this by employing other averages (such as the
      median or the geometric mean) or discarding outliers, though as far as we know
      nobody has evaluated which method performs best under low-replication settings.
      Here we use computer simulations to compare the performance of different methods
      used in low-replication experiments (<=4 cultures). Besides the customary
      averages of mutant frequency, we also tested two well-known fluctuation methods.
      Contrary to common practice, our results support that fluctuation methods should
      be applied in such circumstances, as they perform as well as or better than any
      average of mutant frequency. In particular, experimentalists will benefit from
      using MSS maximum likelihood in low-replication experiments because it: (i)
      provides more reproducible results, (ii) allows for direct estimation of mutation
      rate and (iii) allows for the application of conventional statistics.

PMID- 21736882
TI  - Base excision repair efficiency and mechanism in nuclear extracts are influenced
      by the ratio between volume of nuclear extraction buffer and nuclei-implications
      for comparative studies.
AB  - The base excision repair (BER) pathway corrects many different DNA base lesions
      and is important for genomic stability. The mechanism of BER cannot easily be
      investigated in intact cells and therefore in vitro methods that reflect the in
      vivo processes are in high demand. Reconstitution of BER using purified proteins
      essentially mirror properties of the proteins used, and does not necessarily
      reflect the mechanism as it occurs in the cell. Nuclear extracts from cultured
      cells have the capacity to carry out complete BER and can give important
      information on the mechanism. Furthermore, candidate proteins in extracts can be
      inhibited or depleted in a controlled way, making defined extracts an important
      source for mechanistic studies. The major drawback is that there is no
      standardized method of preparing nuclear extract for BER studies, and it does not
      appear to be a topic given much attention. Here we have examined BER activity of
      nuclear cell extracts from HeLa cells, using as substrate a circular DNA molecule
      with either uracil or an AP-site in a defined position. We show that BER activity
      of nuclear extracts from the same batch of cells varies inversely with the volume
      of nuclear extraction buffer relative to nuclei volume, in spite of identical
      protein concentrations in the BER assay mixture. Surprisingly, the uracil-DNA
      glycosylase activity (mainly UNG2), but not amount of UNG2, also correlated
      negatively with the volume of extraction buffer. These studies demonstrate that
      the method for preparation of nuclear extract is an important factor to consider
      for in vitro BER analysis and conditions used in comparative studies must be
      carefully worked out.

PMID- 21736883
TI  - Therapeutic window of opportunity for the neuroprotective effect of valproate
      versus the competitive AMPA receptor antagonist NS1209 following status
      epilepticus in rats.
AB  - Epileptogenesis, i.e., the process leading to epilepsy, is a presumed consequence
      of brain insults including head trauma, stroke, infections, tumors, status
      epilepticus (SE), and complex febrile seizures. Typically, brain insults produce
      morphological and functional alterations in the hippocampal formation, including
      neurodegeneration in CA1, CA3, and, most consistently, the dentate hilus. Most of
      these alterations develop gradually, over several days, after the insult,
      providing a therapeutic window of opportunity for neuroprotective agents in the
      immediate post-injury period. We have previously reported that prolonged (four
      weeks) treatment with the antiepileptic drug valproate (VPA) after SE prevents
      hippocampal damage and most of the behavioral alterations that occur after brain
      insult, but not the development of spontaneously occurring seizures. These data
      indicated that VPA, although not preventing epilepsy, might be an effective
      disease-modifying treatment following brain insult. The present study was
      designed to (1) determine the therapeutic window for the neuroprotective effect
      of VPA after SE; (2) compare the efficacy of different intermittent i.p. versus
      continuous i.v. VPA treatment protocols; and (3) compare VPA with the glutamate
      (AMPA) receptor antagonist NS1209. As in our previous study with VPA, SE was
      induced by sustained electrical stimulation of the basolateral amygdala in rats
      and terminated after 4 h by diazepam. In vehicle controls, >90% of the animals
      developed significant neurodegeneration in the dentate hilus, whereas damage in
      CA1 and CA3 was more variable. Hilar parvalbumin-expressing interneurons were
      more sensitive to the effects of seizures than somatostatin-stained hilar
      interneurons or hilar mossy cells. Among the various VPA treatment protocols,
      continuous infusion of VPA for 24 immediately following the SE was the most
      effective neuroprotective treatment, preventing most of the neuronal damage.
      Infusion with NS1209 for 24 h exhibited similar neuroprotective efficacy. These
      data demonstrate that short treatment after SE with either VPA or NS1209 is
      powerfully neuroprotective, and may be disease-modifying treatments following
      brain insult.

PMID- 21736884
TI  - The cannabinoid receptor CB1 inverse agonist AM251 potentiates the anxiogenic
      activity of urocortin I in the basolateral amygdala.
AB  - The basolateral amygdala is reported to play an important role in the neural
      bases of emotional processing. Previous studies have shown that injections of
      urocortin I (UcnI) into the basolateral amygdala (BLA) elicit anxiety-like
      behaviors in animal models. The present study examined the anxiogenic effects of
      UcnI administered directly into the BLA of male Sprague-Dawley rats. UcnI was
      administered at doses of 0.1-10.0 pmol and rats were then placed in an elevated
      plus maze for 10 min. UcnI reliably decreased the percent time spent in the open
      arms of the elevated plus maze (EPM) as well as open arm entries. This effect was
      observed across all doses tested, indicating the induction of anxiety-like
      behavior. In separate groups of rats, the CB(1) inverse agonist AM251 was
      administered systemically (0.03-3.0 mg/kg IP) or directly into the BLA (0.25-25.0
      pmol) and EPM performance assessed. Both routes of AM251 administration produced
      a reduction in open arm entries and in time spent in the open arms. Moreover,
      when rats were pretreated with AM251 either systemically or directly into the
      BLA, the anxiogenic effect of UcnI was potentiated. That is, co-administration of
      AM251 and UcnI produced a greater suppression of percent time spent in the open
      arms and open arm entries as compared to UcnI alone. Based on these findings, we
      propose that urocortin and endocannabinoid signaling are part of an integrated
      neural axis modulating anxiety states within the basolateral amygdala. This
      article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21736885
TI  - Blockade of kappa opioid receptors attenuates the development of depressive-like
      behaviors induced by cocaine withdrawal in rats.
AB  - Drug dependence is characterized by dysregulation of brain reward systems and
      increased sensitivity to stress. Chronic exposure to drugs of abuse is associated
      with increased expression of the neuropeptide dynorphin, the endogenous ligand
      for kappa opioid receptors (KORs). Activation of KORs causes depressive- and
      aversive-like responses in rodents, raising the possibility that drug-induced
      upregulation of dynorphin plays a role independence-associated negative states.
      Here we used "binge" exposure to cocaine (3 daily intraperitoneal injections of
      15 mg/kg for 14 days) to examine the development of dependence-like behavior in
      the intracranial self-stimulation (ICSS) test and the forced swim test (FST).
      When rats were tested 1 h before their first scheduled injection of each day-a
      period of drug withdrawal corresponding to 20 h after their last injection on the
      previous day-there were exposure-dependent increases in ICSS thresholds (a
      putative indicator of anhedonia) and decreases in latencies to immobility in the
      FST (a putative indicator of behavioral despair). Administration of the long
      lasting KOR antagonist norBNI (20 MUg, intracerebroventricular) before the
      beginning of the binge regimen attenuated the development of cocaine withdrawal
      induced anhedonia in the ICSS test. In contrast, administration of norBNI in the
      midst of the binge regimen had no effect on expression of cocaine withdrawal
      induced anhedonia in the ICSS test, although it did attenuate despair-like
      behavior in the FST. These data suggest that blockade of KORs before exposure to
      a stressor (in this case, cocaine withdrawal or forced swimming) can attenuate
      the development of stress-induced behavioral adaptations. This article is part of
      a Special Issue entitled 'Anxiety and Depression'.

PMID- 21736886
TI  - Impact of seizure activity on free extracellular phenytoin concentrations in
      amygdala-kindled rats.
AB  - Access of antiepileptic drugs (AEDs) to the epileptic focus region is considered
      to be influenced by seizure-associated changes in blood-brain barrier (BBB)
      function and blood flow. Enhanced leakiness of the BBB has been reported as a
      consequence of seizure activity, and this is controversially discussed to either
      favor accumulation of AEDs in epileptic tissue or to limit free extracellular
      concentrations of AEDs due to enhanced protein extravasation. On the other hand,
      multidrug transporter overexpression has been described following seizure
      activity, which can limit brain penetration of AEDs in brain regions involved in
      seizure generation and spread. Aim of the present study was to determine, how
      these complex alterations at the BBB influence penetration of a standard AED to
      the site of seizure initiation. Microdialysis experiments were performed in
      amygdala-kindled rats and in electrode-implanted, non-kindled rats with the
      microdialysis probe located directly adjacent to the stimulation-recording depth
      electrode. Penetration of the AED phenytoin to the extracellular fluid in the
      focus region was investigated at different time points in relation to seizure
      activity elicited in kindled rats. Integrity of the BBB was determined by Evans
      blue. Access of phenytoin to the amygdala proved to be comparable in non-kindled,
      electrode-implanted control rats and in kindled rats 2 h or fourteen days
      following a single generalized seizure. When a single generalized seizure was
      elicited 10 min following phenytoin administration, average phenytoin brain
      dialysate levels were significantly lower (up to 45%) than those of control
      animals. During a self-sustained status epilepticus, phenytoin access to the site
      of seizure initiation tended to be lower in the early phase following drug
      administration, but reached control level 2 h later. The data clearly demonstrate
      that seizure-induced alterations in BBB integrity and function do not increase
      extracellular brain levels of phenytoin in affected brain regions, but rather
      tend to decrease the free concentration of phenytoin in the extracellular
      compartment.

PMID- 21736887
TI  - Enhancing effects of acetazolamide on neuronal activity correlate with enhanced
      visual processing ability in humans.
AB  - Acetazolamide is a potent inhibitor of the reversible hydration of CO(2)
      catalyzed by the enzyme carbonic anhydrase and is commonly used to increase
      cerebral blood flow e.g. in order to estimate cerebrovascular reserve. However it
      is not known whether acetazolamide may positively affect the excitability of
      neurons in the brain in vivo or cortical processing abilities. To test these
      possibilities we intravenously administered a low dose (7 mg/kg) acetazolamide to
      volunteers who performed a demanding visual signal detection task while
      undergoing whole brain electroencephalographic examinations. Two groups were
      tested twice on the same task, while receiving acetazolamide or a saline
      treatment in between the two sessions. Our data indicate that, while the control
      group showed a decrease in global gamma (30-49 Hz) power across sessions, with no
      correlation to performance, the acetazolamide group showed increased global gamma
      power that strongly related to their performance in the signal detection task.
      This was accompanied by a decrease in the early part of the event related
      potential in the control group, a decrease not seen in the acetazolamide group.
      There were no significant differences in blood pressure, ventilation rate, or
      heart rate between the two groups. It is possible that the differences between
      the groups, observed in this study, are related to the enhancing effect of
      acetazolamide on the nitric oxide generation catalyzed by carbonic anhydrase, or
      to other actions of acetazolamide, e.g. opening of Ca(2+) activated K(+) channels
      and inhibition of Ca(2+) channels.

PMID- 21736889
TI  - Mental rotation impairs attention shifting and short-term memory encoding:
      neurophysiological evidence against the response-selection bottleneck model of
      dual-task performance.
AB  - Dual tasks and their associated delays have often been used to examine the
      boundaries of processing in the brain. We used the dual-task procedure and
      recorded event-related potentials (ERPs) to investigate how mental rotation of a
      first stimulus (S1) influences the shifting of visual-spatial attention to a
      second stimulus (S2). Visual-spatial attention was monitored by using the N2pc
      component of the ERP. In addition, we examined the sustained posterior
      contralateral negativity (SPCN) believed to index the retention of information in
      visual short-term memory. We found modulations of both the N2pc and the SPCN,
      suggesting that engaging mechanisms of mental rotation impairs the deployment of
      visual-spatial attention and delays the passage of a representation of S2 into
      visual short-term memory. Both results suggest interactions between mental
      rotation and visual-spatial attention in capacity-limited processing mechanisms
      indicating that response selection is not pivotal in dual-task delays and all
      three processes are likely to share a common resource like executive control.

PMID- 21736888
TI  - Pharmacological treatment of PTSD - established and new approaches.
AB  - A large proportion of humans will experience a traumatic event at least once in
      their lifetime, with up to 10% then going on to developing posttraumatic stress
      disorder (PTSD). In this review we will discuss established pharmacological
      interventions for PTSD as well as highlight novel therapeutic strategies
      undergoing extensive pre-clinical research as well as ongoing clinical research.
      Such strategies include prophylactic treatments and use of pharmacotherapy as
      adjunctive treatment with established trauma-focused psychological therapies.
      These potential treatment approaches include modulation of stress effects on
      memory consolidation after trauma (e.g., glucocorticoid, corticotropin-releasing
      factor and norepinephrine signalling modulators), as well as putative cognitive
      enhancers that target mechanisms of conditioned fear extinction and
      reconsolidation (e.g., glucocorticoid receptor modulators and modulators of
      glutamate signalling such as positive allosteric modulators of glutamate
      receptors, glycine transporter inhibitors, or glycine agonists). We will discuss
      evidence for and against these potential novel treatment strategies and their
      limitations. This article is part of a Special Issue entitled 'Post-Traumatic
      Stress Disorder'.

PMID- 21736890
TI  - Continuous theta-burst stimulation to primary motor cortex reduces the
      overproduction of forces following removal of visual feedback.
AB  - Forward models, generated from the efference copies of motor commands, are
      thought to monitor the accuracy of ongoing movement. By comparing predicted with
      actual afferent information, forward models also aid in the differentiation of
      self-produced movements from externally generated ones. Many have proposed that a
      consequence of this comparison is attenuation of the predicted component of
      incoming sensory signals. Previous work from our laboratory has shown that
      following the removal of an external visual reference, discrete sequential forces
      exceed target values. Forces produced at the fingertip were perceived as weaker,
      which lead to a systematic, compensatory over-production of the magnitudes
      required. The relatively new repetitive TMS protocol of continuous theta-burst
      stimulation (cTBS) has been shown to reliably depress cortical excitability for a
      period following stimulation. If sensory attenuation mechanisms were responsible
      for the overproduction of forces found in our previous results, we hypothesized
      that reducing cortical excitability of M1 through application of cTBS would
      induce discrepancy between the efference copy generated and motor output
      produced. As a result, we expected the overproduction of forces following visual
      feedback removal would be reduced after receiving cTBS. Participants produced
      series of pinch grip forces in time to a metronome and to visually specified
      force magnitudes. Visual feedback of force output was extinguished 10s into
      experimental trials and participants performed continued responses for the
      remaining 10s. Results confirmed our hypothesis. Mean peak force and constant
      error were greater and more positive in the absence of visual feedback regardless
      of stimulation condition; however, the magnitude of increase was significantly
      reduced following cTBS compared with baseline and sham conditions. Variability
      was not differentially affected by stimulation condition, increasing only with
      removal of visual feedback contingent upon the larger forces produced in these
      trials. Our findings provide further evidence to support the idea that TBS may
      differentially affect motor output and efference copy generation.

PMID- 21736891
TI  - Familiar smiling faces in Alzheimer's disease: understanding the positivity
      related recognition bias.
AB  - Recent research has revealed a recognition bias favoring positive faces and other
      stimuli in older compared to younger adults. However, it is yet unclear whether
      this bias reflects an age-related preference for positive emotional stimuli, or
      an affirmatory bias used to compensate for episodic memory deficits. To follow up
      this point, the present study examined recognition of emotional faces and current
      mood state in patients with mild Alzheimer disease (AD) and healthy controls.
      Expecting lower overall memory performance, more negative and less positive mood
      in AD patients, the critical question was whether the positivity-related
      recognition bias would be increased compared to cognitively unimpaired controls.
      Eighteen AD patients and 18 healthy controls studied happy, neutral, and angry
      faces, which in a subsequent recognition task were intermixed with 50% distracter
      faces. As expected, the patient group showed reduced memory performance, along
      with a less positive and more negative mood. The recognition bias for positive
      faces persisted. This pattern supports the view that the positivity-induced
      recognition bias represents a compensatory, gist-based memory process that is
      applied when item-based recognition fails.

PMID- 21736892
TI  - Lipidomic changes in rat liver after long-term exposure to ethanol.
AB  - Alcoholic liver disease (ALD) is a serious health problem with significant
      morbidity and mortality. In this study we examined the progression of ALD along
      with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the
      mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5%
      ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet.
      Animals were killed at the end of 2 and 3 months and plasma and livers were
      collected. Portions of the liver were fixed for histological and
      immunohistological studies. Plasma and the liver lipids were extracted and
      analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty
      infiltration was observed in the livers of ethanol-fed rats. Mild inflammation
      and oxidative stress were observed in some ethanol-fed rats at 3 months. The
      multivariate and principal component analysis of proton and phosphorus NMR
      spectroscopy data of extracted lipids from the plasma and livers showed
      segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic
      lipids that were increased by ethanol exposure included fatty acids and
      triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free
      fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty
      acyl chains increased, contrary to plasma, where it decreased. Our studies
      confirm that over-accumulation of lipids in ethanol-induced liver steatosis
      accompanied by mild inflammation on long duration of ethanol exposure. Identified
      metabolic profile using NMR lipidomics could be further explored to establish
      biomarker signatures representing the etiopathogenesis, progression and/or
      severity of ALD.

PMID- 21736893
TI  - Quick and reliable assessment of chronological life span in yeast cell
      populations by flow cytometry.
AB  - Yeast chronological life span (CLS) is defined as the capacity of stationary
      cultures to maintain viability over time, thus mimicking the situation of post
      mitotic cells in multicellular organisms. Cellular viability is typically
      determined by using the colony formation unit assay (CFU). CFU counting is simple
      but laborious and does not accommodate large-scale experiments. Importantly,
      viability is determined on the basis of the cell's ability to divide and form a
      colony, probably not the ideal parameter when studying post-mitotic cellular
      ageing. This study describes the optimization and validation of a method based on
      the flow cytometric monitoring of propidium iodide (PI) uptake for assessing
      yeast cell death during CLS. The optimized protocol is quick, reliable,
      reproducible and can accommodate high-throughput studies. The method was
      validated by determining CLS of several strains used in yeast ageing research and
      by evaluating the effect of genetic disturbances known to extend or reduce yeast
      chronological life span.

PMID- 21736894
TI  - The role of the microenvironment in tumor growth and invasion.
AB  - Mathematical modeling and computational analysis are essential for understanding
      the dynamics of the complex gene networks that control normal development and
      homeostasis, and can help to understand how circumvention of that control leads
      to abnormal outcomes such as cancer. Our objectives here are to discuss the
      different mechanisms by which the local biochemical and mechanical
      microenvironment, which is comprised of various signaling molecules, cell types
      and the extracellular matrix (ECM), affects the progression of potentially
      cancerous cells, and to present new results on two aspects of these effects. We
      first deal with the major processes involved in the progression from a normal
      cell to a cancerous cell at a level accessible to a general scientific
      readership, and we then outline a number of mathematical and computational issues
      that arise in cancer modeling. In Section 2 we present results from a model that
      deals with the effects of the mechanical properties of the environment on tumor
      growth, and in Section 3 we report results from a model of the signaling pathways
      and the tumor microenvironment (TME), and how their interactions affect the
      development of breast cancer. The results emphasize anew the complexities of the
      interactions within the TME and their effect on tumor growth, and show that tumor
      progression is not solely determined by the presence of a clone of mutated
      immortal cells, but rather that it can be 'community-controlled'.

PMID- 21736895
TI  - The role of opioid antagonist efficacy and constitutive opioid receptor activity
      in the opioid withdrawal syndrome in mice.
AB  - On the basis of efficacy, opioid antagonists are classified as inverse opioid
      agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6beta-naltrexol).
      This study examined the interaction between naltrexone and 6beta-naltrexol in the
      precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore,
      the possible contribution of constitutive opioid receptor activity to
      precipitated withdrawal was evaluated using increasing levels of morphine
      dependence. In the first experiment, low doses of 6beta-naltrexol antagonized
      naltrexone precipitated withdrawal while high doses acted additively. All doses
      of naltrexone increased 6beta-naltrexol's potency to precipitate withdrawal. The
      next experiment examined changes in antagonist potency to precipitate withdrawal
      with increasing morphine dependence. Mice were exposed to morphine for 1-6 days
      and then withdrawal was precipitated. Naltrexone was more potent than 6beta
      naltrexol at all the time points. The ED(50) of both drugs decreased at the same
      rate suggesting that increased dependence produced no change in constitutive
      opioid receptor activity. Taken together these results indicate that the
      functional efficacy of 6beta-naltrexol is dose-dependent and that constitutive
      opioid receptor activity did not change as opioid dependence increased from 1 to
      6 days.

PMID- 21736896
TI  - Trifluoroethanol stabilizes the molten globule state and induces non-amyloidic
      turbidity in stem bromelain near its isoelectric point.
AB  - Stem bromelain (SBM) is a therapeutic protein that has been studied for alkaline
      denaturation in the intestines, the principal site of its absorption. In this
      study, we investigated fluorinated alcohol 2,2,2-trifluoroethanol (TFE)-induced
      conformational changes in the specific/pre-molten globule (SMG) state of SBM
      observed at pH 10 by spectroscopic methods. Far-UV circular dichroism (CD)
      spectra showed that the protein retained its native-like secondary structure at
      TFE concentrations of up to 30% with a pronounced minimum at 222 nm,
      characteristic of a helix. However, addition of slightly higher TFE
      concentrations (>=40%) resulted in an ~2.5-fold induction of this helical feature
      and a time-dependent increase in non-amyloidic turbidity as evidenced by
      turbidometric, Congo red-binding, and Thioflavin T (ThT)-binding studies. Near-UV
      CD spectra suggested a gradual but significant loss of tertiary structure at 10
      30% TFE. Tryptophan studies showed blue-shifted fluorescence, although the number
      of accessible tryptophans remained the same up to 30% TFE. The SMG showed
      enhanced binding of the fluorescent probe 1-anilino-8-naphthalene sulfonic acid
      (ANS) up to 30% TFE, beyond which binding plateaued. Thermal and guanidine
      hydrochloride (GdnHCl) transition studies in the near-UV range indicated a single
      cooperative transition for the SMG state in the presence of 30% TFE, similar to
      that observed for native SBM at pH 7.0 (although with different T(m)s), unlike
      the SMG state. TFE (30%) appeared to induce native-like stability to the original
      SMG. These observations suggest a transformation of the SMG to a characteristic
      molten globule (MG) conformation at 30% TFE, possibly due to TFE-induced
      rearrangement of hydrophobic interactions at the protein's isoelectric point.

PMID- 21736897
TI  - Molecular cloning, characterization and expression analysis of the tumor necrosis
      factor (TNF) superfamily gene, TNF receptor superfamily gene and
      lipopolysaccharide-induced TNF-alpha factor (LITAF) gene from Litopenaeus
      vannamei.
AB  - In vertebrates, the tumor necrosis factor (TNF)-receptor (TNFR) system
      participates in diverse physiological and pathological events, such as
      inflammation and protective immune responses to microbial infections. There are
      few reports about the role of the invertebrate TNF-TNFR system in immune
      responses. Here, we isolated and characterized the TNF superfamily (LvTNFSF)
      gene, TNFR superfamily (LvTNFRSF) gene and lipopolysaccharide-induced TNF-alpha
      factor (LvLITAF) gene from Litopenaeus vannamei. LvTNFSF consists of 472 amino
      acids with a conserved C-terminal TNF domain and has 89.8% identity with the
      Marsupenaeus japonicus TNF superfamily gene. LvTNFRSF consists of 296 amino acids
      with a conserved TNFR domain and has 18.0% identity with Chlamys farreri TNFR,
      14.6% identity with Drosophila melanogaster Wengen and 14.6% identity with Homo
      sapiens TNFR1. LvLITAF consists of 124 amino acids with the LITAF domain and
      shows 62.6% identity with D. melanogaster LITAF and 32.3% identity with H.
      sapiens LITAF. The promoter region of LvTNFSF was cloned and used to construct a
      luciferase reporter. In Drosophila S2 cells, the promoter of LvTNFSF can be
      activated by LvLITAF, L. vannamei NF-kappaB family proteins (LvRelish and
      LvDorsal) and LvSTAT. Unlike its mammalian counterparts, LvTNFRSF could not
      activate the NF-kappaB pathway in Drosophila S2 cells. Using real-time
      quantitative PCR, we obtained expression profiles of LvTNFSF, LvTNFRSF and
      LvLITAF in the gill, intestine and hepatopancreas of L. vannamei after challenge
      with Gram-negative Vibrio alginolyticus, Gram-positive Staphylococcus aureus, the
      fungus Candida albicans and white spot syndrome virus (WSSV). Taken together, our
      results reveal that LvTNFSF, LvTNFRSF and LvLITAF may be involved in shrimp
      immune responses to pathogenic infections.

PMID- 21736898
TI  - Localization of presynaptic inputs on dendrites of individually labeled neurons
      in three dimensional space using a center distance algorithm.
AB  - The spatial distribution of synaptic inputs on the dendritic tree of a neuron can
      have significant influence on neuronal function. Consequently, accurate
      anatomical reconstructions of neuron morphology and synaptic localization are
      critical when modeling and predicting physiological responses of individual
      neurons. Historically, generation of three-dimensional (3D) neuronal
      reconstructions together with comprehensive mapping of synaptic inputs has been
      an extensive task requiring manual identification of putative synaptic contacts
      directly from tissue samples or digital images. Recent developments in neuronal
      tracing software applications have improved the speed and accuracy of 3D
      reconstructions, but localization of synaptic sites through the use of pre-
      and/or post-synaptic markers has remained largely a manual process. To address
      this problem, we have developed an algorithm, based on 3D distance measurements
      between putative pre-synaptic terminals and the post-synaptic dendrite, to
      automate synaptic contact detection on dendrites of individually labeled neurons
      from 3D immunofluorescence image sets. In this study, the algorithm is
      implemented with custom routines in Matlab, and its effectiveness is evaluated
      through analysis of primary sensory afferent terminals on motor neurons.
      Optimization of algorithm parameters enabled automated identification of synaptic
      contacts that matched those identified by manual inspection with low incidence of
      error. Substantial time savings and the elimination of variability in contact
      detection introduced by different users are significant advantages of this
      method.

PMID- 21736899
TI  - Complementary activation of hippocampal-cortical subregions and immature neurons
      following chronic training in single and multiple context versions of the water
      maze.
AB  - Neurobiological studies of memory typically involve single learning sessions that
      last minutes or days. In natural settings, however, animals are constantly
      learning. Here we investigated how several weeks of spatial water maze training
      influences subsequent activation of neocortical and hippocampal subregions,
      including adult-born neurons. Mice were either trained in a single context or in
      a variant of the task in which the spatial cues and platform location changed
      every 3 days, requiring constant new learning. On the final day, half of the mice
      in each training group were tested in a novel context and the other half were
      tested in their previous, familiar context. Two hours later mice were perfused to
      measure subregion-specific expression of the immediate-early gene zif268, a
      marker of neuronal activation. None of the training paradigms affected the
      magnitude of adult neurogenesis. However, different neuronal populations were
      activated depending on prior training history, final context novelty, or a
      combination of these 2 factors. The anterior cingulate cortex was more activated
      by novel context exposure, regardless of the type of prior training. The
      suprapyramidal blade of the dentate gyrus and region CA3 showed greater
      activation in mice trained in multiple contexts, primarily after exposure to a
      familiar context. In immature granule neurons, multiple context training enhanced
      activation regardless of final context novelty. CA1 showed no significant changes
      in zif268 expression across any training condition. In naive control mice,
      training on the final day increased zif268 expression in CA3, CA1 and the
      anterior cingulate cortex, but not the dentate gyrus, relative to mice that
      remained in their cages (transport controls). Unexpectedly, immature granule
      cells showed a decrease in zif268 expression in naive learners relative to
      transport controls. These findings suggest novel and complementary roles for
      hippocampal, neocortical, and immature neuronal populations in learning and
      memory.

PMID- 21736900
TI  - Could adult hippocampal neurogenesis be relevant for human behavior?
AB  - Although the function of adult neurogenesis is still unclear, tools for directly
      studying the behavioral role of new hippocampal neurons now exist in rodents.
      Since similar studies are impossible to do in humans, it is important to assess
      whether the role of new neurons in rodents is likely to be similar to that in
      humans. One feature of adult neurogenesis that varies tremendously across species
      is the number of neurons that are generated, so a key question is whether there
      are enough neurons generated in humans to impact function. In this review we
      examine neuroanatomy and circuit function in the hippocampus to ask how many
      granule neurons are needed to impact hippocampal function and then discuss what
      is known about numbers of new neurons produced in adult rats and humans. We
      conclude that relatively small numbers of neurons could affect hippocampal
      circuits and that the magnitude of adult neurogenesis in adult rats and humans is
      probably larger than generally believed.

PMID- 21736901
TI  - Differential expression of proteins in antimony-susceptible and -resistant
      isolates of Leishmania donovani.
AB  - Visceral Leishmaniasis (VL) is a parasitic disease caused by the protozoan
      parasite Leishmania donovani. Resistance to pentavalent antimonials (SbV), the
      mainstay therapy for leishmaniasis is now a major concern, due to emergence of
      drug resistance. Hence, understanding the underlying mechanism of resistance to
      antimonials is required. Here we used quantitative mass spectrometery to identify
      global proteome differences between antimony-susceptible/-resistant isolates. We
      detected modification of expression of proteins involved in the key metabolic
      pathways. Comparative proteomic analysis indicated increase in glycolysis in the
      antimony-resistant isolates. Elevated expression of stress related proteins
      implicated in oxidative stress was observed in the resistant parasites. Most
      importantly, we observed upregulation of proteins that may have a role in
      intracellular survival of the parasite in the resistant isolates. The identified
      parasite proteins could serve as surrogate markers for resistance or
      susceptibility and would also help in understanding the underlying mechanism of
      resistance to antimonials.

PMID- 21736902
TI  - Thrombin activation of PI3K/PDK1/Akt signaling promotes cyclin D1 upregulation
      and RPE cell proliferation.
AB  - The retinal pigment epithelium (RPE) plays an essential role in the survival and
      function of the neural retina. RPE uncontrolled proliferation leads to the
      development of proliferative ocular pathologies, among which proliferative
      vitreoretinopathy (PVR) is the main cause of retinal surgery failure. Upon the
      breakdown of the BRB due to trauma or metabolic imbalance the contact of RPE with
      serum-contained thrombin has been shown to stimulate the proliferation of
      otherwise quiescent RPE cells. Although the molecular mechanisms involved in this
      effect are still undetermined, thrombin proteolytic activation of protease
      activated G protein coupled receptor-1 (PAR-1) activates PI3K and Akt, known to
      play an essential role in proliferation. The present study demonstrates that: 1)
      thrombin stimulates Ser 473 Akt phosphorylation without affecting Thr 308 basal
      phosphorylation in RPE cells; 2) thrombin-induced Akt stimulation promotes cyclin
      D1 accumulation through the phosphorylation/ inhibition of GSK-3beta, thus
      preventing Thr 286 cyclin D1 phosphorylation, nuclear export and degradation; 3)
      Akt signaling requires the upstream activation of PI3K and PLC. Since the
      pharmacological inhibition of these pathways or the silencing of cyclin
      expression prevent thrombin-induced RPE cell proliferation, these results
      contribute relevant evidence for establishing the mechanism involved in the
      development of proliferative eye diseases.

PMID- 21736904
TI  - Viability of respiratory pathogens cultured from nasopharyngeal swabs stored for
      up to 12 years at -70 degrees C in skim milk tryptone glucose glycerol broth.
AB  - Nasopharyngeal carriage studies are needed to monitor changes in important
      bacterial pathogens in response to vaccination and antibiotics. The ability to
      store original specimens frozen in skim milk tryptone glucose glycerol broth
      (STGGB) allows additional studies to be conducted without the need for further
      expensive field collection. Although sub-cultured isolates remain viable in this
      medium for many years, limited data are available to indicate viability of
      relatively low numbers of organisms present in nasopharyngeal specimens stored
      frozen over long periods of time. We conducted several studies whereby swabs
      stored in STGGB at -70 degrees C for up to 12 years were thawed and aliquots
      cultured. Recovery of Streptococcus pneumoniae (72% positive from 269 swabs),
      Haemophilus influenzae (62% from 214) and Moraxella catarrhalis (81% from 162)
      was not significantly different from the original cultures: 69% (Risk Difference
      [RD] 3.0, 95% Confidence Interval [CI] -4.7, 10.7), 66% (RD -4.7, 95% CI -13.8,
      4.4) and 78% (RD 3.1, 95% CI -5.7, 11.9) positive respectively. There was no
      trend in recovery from swabs stored for increasing lengths of time. We conclude
      that studies which rely on the viability of these respiratory pathogens can be
      conducted using original swabs stored at -70 degrees C for at least 12 years.

PMID- 21736903
TI  - ClpXP, an ATP-powered unfolding and protein-degradation machine.
AB  - ClpXP is a AAA+ protease that uses the energy of ATP binding and hydrolysis to
      perform mechanical work during targeted protein degradation within cells. ClpXP
      consists of hexamers of a AAA+ ATPase (ClpX) and a tetradecameric peptidase
      (ClpP). Asymmetric ClpX hexamers bind unstructured peptide tags in protein
      substrates, unfold stable tertiary structure in the substrate, and then
      translocate the unfolded polypeptide chain into an internal proteolytic
      compartment in ClpP. Here, we review our present understanding of ClpXP structure
      and function, as revealed by two decades of biochemical and biophysical studies.

PMID- 21736905
TI  - Kinetics of production and characterization of the fucose-containing
      exopolysaccharide from Enterobacter A47.
AB  - A fucose-containing exopolysaccharide (EPS) was produced by the bacterium
      Enterobacter A47 using glycerol byproduct from the biodiesel industry. The
      analysis of kinetic data suggested a partially growth associated EPS synthesis
      model. Although the EPS was composed of fucose, galactose and glucose at all
      cultivation stages, their relative proportion has varied considerably during the
      run. At the beginning (24h), glucose was the main component (82.4 wt.%), being
      fucose and galactose minor components (5.0 wt.% and 10.9 wt.%, respectively),
      while at the end (96 h) it was composed of 26.0 wt.% fucose, 28.9 wt.% galactose
      and 43.7 wt.% glucose. The acyl groups content and composition have also changed,
      reaching their maximum content (19.2wt.%) at the end of the run. Moreover, the
      molecular weight has increased linearly during the run (from 8*10(5) to 5*10(6)).
      The changes observed in EPS composition and molecular weight have also had an
      impact upon the polymer's intrinsic viscosity, as shown by its linear increase
      from 3.95 to 10.72 dL g(-1). The results suggest that the culture might have
      synthesized at least two distinct EPS, with different sugar composition and
      average molecular weight, which predominated at different cultivation stages.

PMID- 21736906
TI  - Mycoviruses infecting the endophytic and entomopathogenic fungus Tolypocladium
      cylindrosporum.
AB  - A mixed virus infection in a strain of the endophytic and entomopathogenic fungus
      Tolypocladium cylindrosporum was deduced from a study of the transmission to
      conidia of several double-stranded RNA (dsRNA) elements. The transmission rates
      of each dsRNA were different, and monosporic isolates harbouring different
      combinations of the original set of six dsRNAs were obtained. A 5196 bp dsRNA
      element was sequenced and represents the genome of T. cylindrosporum virus 1
      (TcV1), a new member of the genus Victorivirus in the Totiviridae family. This
      virus was transmitted to 81.4% of the conidia; in contrast, four dsRNAs of 3.1
      3.7 kbp were transmitted only to 4.7% of the monosporic isolates obtained from
      the infected parental strain. These four dsRNAs did not show segregation during
      transmission, and one of them was shown by sequence analysis to encode an RdRp,
      suggesting that the four molecules might represent the whole genome of a
      quadripartite chrysovirus. A third possible virus with a genome of approximately
      4.2 kbp was transmitted to 79.1% of the monosporic isolates produced by the
      infected strain. Ribavirin was used to cure T. cylindrosporum from viruses, and
      TcV1 was sensitive to this drug. All monosporic cultures derived from the
      infected strain treated with 80 and 100 MUM concentrations of the drug were free
      of TcV1.

PMID- 21736907
TI  - U.S. consumers attitudes toward farm animal cloning.
AB  - In January 2008, the United States Food and Drug Administration concluded "meat
      and milk from cattle, swine, and goat clones or their offspring are as safe to
      eat as food we eat from those species now" (U.S. FDA, 2010). However, cloning
      remains a very controversial topic. A web-based survey administered by Knowledge
      Networks was used to determine U.S. consumers' awareness of and attitudes toward
      meat and milk from cloned cattle. Findings reveal consumers do not differentiate
      much between products from cloned animals and products from non-cloned animals.
      Overall consumers are concerned that animal cloning is an unnatural process and
      that it will lead to human cloning.

PMID- 21736908
TI  - Growth-inhibition effects of pacifastin-like peptides on a pest insect: the
      desert locust, Schistocerca gregaria.
AB  - The main reason for the varying degrees of success of peptidase inhibitors (PI)
      as biological insecticides is the existence of a poorly understood mechanism,
      which allows pest insects to compensate for PI present in their diet. To
      challenge this highly flexible physiological mechanism and to prolong the
      inhibitory effect of PI on insect growth, a number of measures were taken into
      account before and during experiments with a notorious pest insect, the desert
      locust, Schistocerca gregaria: (i) non-plant PI (pacifastin-related inhibitors)
      were used to reduce the risk of a specific co-evolutionary adaptation of the pest
      insect, (ii) based on the main types of digestive enzymes present in the midgut,
      mixtures of multiple PI with different enzyme specificity were selected, allowing
      for a maximal inhibition of the proteolytic activity and (iii) digestive
      peptidase samples were taken during oral administration experiments to study
      compensatory mechanisms. Contrary to larvae fed on a diet containing plant
      derived PI, a significant growth impediment was observed in larvae that were fed
      a mixture of different pacifastin-like PI. Nevertheless, the growth inhibition
      effect of this PI mixture attenuated after a few days, Moreover, a comprehensive
      study of the observed responses after oral administration of PI revealed that S.
      gregaria larvae can adjust their secreted digestive enzyme activities in two
      distinct ways depending on the composition/concentration of the PI-mixture.

PMID- 21736909
TI  - Developmental effects of ghrelin.
AB  - Ghrelin is a pleiotropic hormone that was originally described as promoting
      feeding and stimulating growth hormone release in adults. A growing body of
      evidence suggests that ghrelin may also exert developmental and organizational
      effects during perinatal life. The perinatal actions of ghrelin include the
      regulation of early developmental events such as blastocyst development and
      perinatal growth. Moreover, alterations in perinatal ghrelin levels result in
      structural differences in various peripheral organs, such as the pancreas and
      gastrointestinal tract. Recent data have also suggested that ghrelin acts on
      appetite-related brain centers in early life. Together, these observations
      indicate that exposure to factors that alter how ghrelin impacts development may
      induce lasting effects on physiological regulation.

PMID- 21736910
TI  - Identification of an antifungal peptide from Trapa natans fruits with inhibitory
      effects on Candida tropicalis biofilm formation.
AB  - Due to recent emergence of fungal pathogens resistant to current antifungal
      therapies, several studies have been focused on screening of plant peptides to
      find novel compounds having antifungal activities. Here, a novel antifungal plant
      peptide, with molecular mass of 1230 Da was purified from fruits of Trapa natans
      by reverse phase high performance liquid chromatography using 300SB-C18 column
      and named as Tn-AFP1. Determination of complete amino acid sequences of this
      peptide by tandem mass spectrometry showed to contain following eleven amino acid
      residues: LMCTHPLDCSN. Purified Tn-AFP1 showed the inhibition of Candida
      tropicalis growth in vitro and disrupted the biofilm formation in a concentration
      dependent manner. It also showed downregulation of MDR1 and ERG11 gene expression
      in real time-PCR analysis. In silico molecular modeling predicted the structure
      of Tn-AFP1 as a single coil attached by a unique disulfide bond. Characterization
      of Tn-AFP1 could contribute in designing novel derivative(s) of this peptide for
      the development of more effective antimycotic compounds.

PMID- 21736911
TI  - The influence and the mechanism of docosahexaenoic acid on a mouse model of
      Parkinson's disease.
AB  - This study aimed to investigate the effects of docosahexaenoic acid (DHA) on the
      oxidative stress that occurs in an experimental mouse model of Parkinson's
      disease (PD). An experimental model of PD was created by four intraperitoneal
      injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 * 20 mg/kg,
      at 12h intervals). Docosahexaenoic acid was given daily by gavage for 4 weeks (36
      mg/kg/day). The motor activity of the mice was evaluated via the pole test, and
      the dopaminergic lesion was determined by immunohistochemical analysis for
      tyrosine hydroxylase (TH)-immunopositive cells. The activity of antioxidant
      enzymes in the brain were determined by spectrophotometric assays and the
      concentration of thiobarbituric acid-reactive substances (TBARS) were measured as
      an index of oxidative damage. The number of apoptotic dopaminergic cells
      significantly increased in MPTP-treated mice compared to controls. Although DHA
      significantly diminished the number of cell deaths in MPTP-treated mice, it did
      not improve the decreased motor activity observed in the experimental PD model.
      Docosahexaenoic acid significantly diminished the amount of cell death in the
      MPTP+DHA group as compared to the MPTP group. TBARS levels in the brain were
      significantly increased following MPTP treatment. Glutathione peroxidase (GPx)
      and catalase (CAT) activities of brain were unaltered in all groups. The activity
      of brain superoxide dismutase (SOD) was decreased in the MPTP-treated group
      compared to the control group, but DHA treatment did not have an effect on SOD
      activity in the MPTP+DHA group. Our current data show that DHA treatment exerts
      neuroprotective actions on an experimental mouse model of PD. There was a
      decrease tendency in brain lipid oxidation of MPTP mice but it did not
      significantly.

PMID- 21736912
TI  - The potential impact of an HIV vaccine with rapidly waning protection on the
      epidemic in Southern Africa: examining the RV144 trial results.
AB  - BACKGROUND: The prime-boost HIV vaccine regimen used in the recent RV144 trial
      resulted in modest efficacy of 31% over 3.5 years, but was substantially higher
      in the first year post-vaccination. We sought to explore the potential impact of
      a vaccine with rapidly waning efficacy in a South African population. METHODS: We
      explored two strategies using a dynamic compartmental epidemic model for
      heterosexual transmission of HIV: [1] vaccination of a single cohort (30%, 60% or
      90% of the initial population), with exponentially waning efficacy, but booster
      vaccinations at 5- or 2-year intervals, and [2] continuous vaccination of the
      unvaccinated population at the same coverage levels (30%, 60% or 90%) but with a
      constant efficacy vaccine of short duration. We also examined potential changes
      in post-vaccination condom use. RESULTS: The single cohort vaccination strategies
      did not have a substantial impact on HIV prevalence, although without boosters
      they still prevented 2-6% of the expected infections at 20 years, depending on
      the population coverage. The 5-year and 2-year booster strategies prevented 8-24%
      and 17-45% of the expected infections, respectively. Continuous vaccination to
      maintain population coverage levels resulted in more substantial reductions in
      population HIV prevalence and greater numbers of infections prevented: HIV
      prevalence at 20 years was reduced from 23% to 8-14% and the number of expected
      infections was decreased by 34-59%, depending on the population coverage level.
      Moderate changes in post-vaccination condom use did not substantially affect
      these outcomes. CONCLUSIONS: An HIV vaccine with partial efficacy and declining
      protection similar to the RV144 vaccine could prevent a substantial proportion of
      HIV infections if booster vaccinations were effective and available. Our
      estimates of the population impact of vaccination would be improved by further
      understanding of the duration of protection, the effectiveness of booster
      vaccination, and whether the vaccine efficacy varies between subpopulations at
      higher and lower risk of exposure.

PMID- 21736913
TI  - Delta inulin polysaccharide adjuvant enhances the ability of split-virion H5N1
      vaccine to protect against lethal challenge in ferrets.
AB  - BACKGROUND: The reduced immunogenicity of the H5 hemagglutinin (HA), compared to
      seasonal HA serotypes, has stimulated searches for effective adjuvants to improve
      H5 vaccine efficacy. This study examined the immunogenicity and protective
      efficacy in ferrets immunized with a split-virion H5N1 vaccine combined with
      AdvaxTM, a novel delta inulin-based polysaccharide adjuvant technology that has
      previously demonstrated ability to augment humoral and cellular immunity to co
      administered antigens. METHODS: Ferrets were vaccinated twice 21 days apart with
      7.5 MUg or 22.5 MUg of a split-virion preparation of A/Vietnam/1203/2004 with or
      without adjuvant. An additional group received just one immunization with 22.5
      MUg HA plus adjuvant. Serum antibodies were measured by hemagglutination
      inhibition and microneutralization assays. Vaccinated animals were challenged
      intranasally 21 days after the last immunization with 10(6) EID(50) of the
      homologous strain. Morbidity was assessed by observed behavior, weight loss,
      temperature, cytopenias, histopathology, and viral load. RESULTS: No serum
      neutralization antibody was detected after two immunizations with unadjuvanted
      vaccine. Two immunizations with high or low dose adjuvanted vaccine stimulated
      high neutralizing antibody titers. Survival was 100% in all groups receiving
      adjuvanted-vaccine including the single dose group, compared to 67% survival with
      unadjuvanted vaccine, and 0% survival in saline or adjuvant-alone controls.
      Minimal morbidity was seen in all animals receiving adjuvanted vaccine, and was
      limited to rhinorrhea and mild thrombocytopenia, without fever, weight loss, or
      reduced activity. H5N1 virus was cleared from the nasal wash by day 4 post
      challenge only in animals receiving adjuvanted vaccine which also prevented viral
      invasion of the brain in most animals. CONCLUSIONS: In this initial study,
      AdvaxTM adjuvant formulations improved the protective efficacy of a split-virion
      H5N1 vaccine as measured by significantly enhanced immunogenicity, survival, and
      reduced morbidity.

PMID- 21736914
TI  - Proteoliposomes from Mycobacterium smegmatis induce immune cross-reactivity
      against Mycobacterium tuberculosis antigens in mice.
AB  - Proteoliposomes (PL) obtained from Mycobacterium smegmatis (Ms) were evaluated
      for their capacity to elicit cross-reactive responses against Mycobacterium
      tuberculosis (Mtb) antigens in BALB/c mice. Animals immunized with PL adjuvanted
      with alum (PL-AL) or Freund's Incomplete Adjuvant (PL-IFA) showed significant IgG
      responses against the PL as well as total Ms lipids. Both groups of animals also
      showed significant IgG responses against BCG, but only animals immunized with PL
      AL produced significant IgG responses against soluble cell wall proteins (SCWP)
      or whole cell lysate (WCL) of Mtb. Significant DTH responses against WCL were
      observed in both groups of animals after 24 h, but only PL-AL-immunized mice
      showed significant DTH responses after 48 h and 72 h. PL-Ms are capable of
      eliciting cross-reactive humoral and cellular responses against Mtb antigens and
      thus may be a potential vaccine strategy against tuberculosis.

PMID- 21736915
TI  - Pandemic influenza A (H1N1) vaccination in The Netherlands: parental reasoning
      underlying child vaccination choices.
AB  - INTRODUCTION: During the 2009 influenza A (H1N1) pandemic, parents in the
      Netherlands were recommended to vaccinate healthy children between six months and
      five years of age. The aim of this study was to examine reasons for (non
      )acceptance, risk perception, feelings of doubt and regret, influence of the
      social network, and information-seeking behavior of parents who accepted or
      declined H1N1 vaccination. METHODS: Data on accepters were collected via exit
      interviews following the second-dose vaccination round in December 2009 (n=1227).
      Data on decliners were gathered in June and July 2010 with questionnaires
      (n=1900); 25 parents participated in in-depth interviews. RESULTS: The most
      reported reasons for parental acceptance of H1N1 vaccination were "I don't want
      my child to become sick" (43%), "Mexican flu can be severe" (10%), "the
      government advises it, so I do it" (6%), and "if I don't do it, I will regret it"
      (6%). The most reported reasons declining the vaccination were "fear of side
      effects/harmful consequences" (51%), "just having a bad feeling about it" (46%),
      and "the vaccine was not thoroughly tested" (39%). More decliners than accepters
      experienced feelings of doubt about the vaccination decision (decliners 63%
      versus accepters 51%, p<0.001), and decliners reported more often information
      seeking behavior (decliners 76% versus accepters 56%, p<0.001). Decliners more
      frequently solicited advice from their social network than accepters (decliners
      72% versus accepters 61%, p<0.001). Furthermore, accepters more often reported
      social influence on their vaccination decision (accepters 58% versus decliners
      38%, p<0.001) and experienced more negative feelings after their vaccination
      decision (accepters 8% versus decliners 2%, p<0.001). Immigrant accepters and
      decliners more often had feelings of doubt and regret about the vaccination
      decision, solicited advice more often from their social network, and were more
      often influenced by this advice compared to native Dutch parents. CONCLUSION: To
      optimize response rates in future vaccination campaigns, health authorities
      should provide more information on vaccine benefits and possible risks, tailoring
      this information to specific risk groups. Health authorities should also invest
      in the development and implementation of effective vaccine risk/benefit
      communication tools.

PMID- 21736916
TI  - Alcohol dependence, disinhibited behavior and variation in the prodynorphin gene.
AB  - The results of the current analyses present preliminary evidence of an
      association between putatively functional variation in the prodynorphin (PDYN)
      gene and a dimensional measure of disinhibited behavior. A 68bp sequence in the
      core promoter region of the PDYN gene was genotyped in a community sample of 1021
      adults aged 30-54. Participants were interviewed for lifetime history of DSM-IV
      alcohol dependence and completed two self-report measures of sensation seeking
      and impulsiveness. Fifteen percent (n=151) of the sample met DSM-IV criteria for
      alcohol dependence and while results did not support an association between the
      PDYN polymorphism and the diagnosis of alcohol dependence, we did observe an
      association between the "low" expressing L allele of the PDYN gene and a
      preference for engaging in disinhibited behavior. Additionally, people who had
      both a history of alcohol dependence and higher scores on this Disinhibited
      Behavior scale were most likely to carry an L allele. These results indicate that
      variation in the PDYN gene is associated with a dimensional trait or intermediate
      phenotype that reflects a preference for heavy drinking and engaging in related
      risky behaviors (e.g., drug use, sexual activity).

PMID- 21736917
TI  - G protein-coupled receptors involved in GnRH regulation: molecular insights from
      human disease.
AB  - In the past two decades, an increasing body of evidence has demonstrated that
      several G protein-coupled receptor (GPCR)-ligand pairs are critical for normal
      human reproductive development and function. Patients harboring genetic insults
      in either the receptors or their cognate ligands have presented with reproductive
      disorders characterized by varying degrees of GnRH deficiency. These disorders
      include idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann Syndrome
      (KS). Conversely, mutations in some of these ligand-receptor pairs have been
      associated with accelerated reproductive maturation, manifested as central
      precocious puberty (CPP). To date, a series of elegant studies have characterized
      four GPCRs that play important roles in the neuroendocrine control of human
      reproductive development and function: GnRHR, KISS1R, PROKR2 and NK3R.
      Furthermore, these studies provide insights into the mechanisms by which
      mutations in these receptors give rise to reproductive disease phenotypes. This
      report will review mutations identified in GPCRs involved in the neuroendocrine
      control of the human reproductive axis with the aims of elucidating structure
      function relationships of these GPCRs and identifying correlations between these
      structure-function relationships and the genotypic-phenotypic characterization of
      the patients.

PMID- 21736918
TI  - Mineralocorticoid and glucocorticoid receptors at the neuronal membrane,
      regulators of nongenomic corticosteroid signalling.
AB  - The balance between corticosteroid actions induced via activation of the
      mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) determines
      the brain's response to stress. While both receptors are best known for their
      delayed genomic role, it has become increasingly evident that they can also
      associate with the plasma membrane and act as mediators of rapid, nongenomic
      signalling. Nongenomic corticosteroid actions in the brain are required for the
      coordination of a rapid adaptive response to stress; membrane-associated MRs and
      GRs play a major role herein. However, many questions regarding the underlying
      mechanism are still unresolved. How do MR and GR translocate to the membrane and
      what are their downstream signalling partners? In this review we discuss these
      issues based on insights obtained from related receptors, most notably the
      estrogen receptor alpha.

PMID- 21736919
TI  - Proteomic analysis of short- and intermediate-term memory in Hermissenda.
AB  - Changes in cellular and synaptic plasticity related to learning and memory are
      accompanied by both upregulation and downregulation of the expression levels of
      proteins. Both de novo protein synthesis and post-translational modification of
      existing proteins have been proposed to support the induction and maintenance of
      memory underlying learning. However, little is known regarding the identity of
      proteins regulated by learning that are associated with the early stages
      supporting the formation of memory over time. In this study we have examined
      changes in protein abundance at two different times following one-trial in vitro
      conditioning of Hermissenda using two-dimensional difference gel electrophoresis
      (2D-DIGE), quantification of differences in protein abundance between conditioned
      and unpaired controls, and protein identification with tandem mass spectrometry.
      Significant regulation of protein abundance following one-trial in vitro
      conditioning was detected 30 min and 3 h post-conditioning. Proteins were
      identified that exhibited statistically significant increased or decreased
      abundance at both 30 min and 3 h post-conditioning. Proteins were also identified
      that exhibited a significant increase in abundance only at 30 min, or only at 3 h
      post-conditioning. A few proteins were identified that expressed a significant
      decrease in abundance detected at both 30 min and 3 h post-conditioning, or a
      significant decrease in abundance only at 3 h post-conditioning. The proteomic
      analysis indicates that proteins involved in diverse cellular functions such as
      translational regulation, cell signaling, cytoskeletal regulation, metabolic
      activity, and protein degradation contribute to the formation of memory produced
      by one-trial in vitro conditioning. These findings support the view that changes
      in protein abundance over time following one-trial in vitro conditioning involve
      dynamic and complex interactions of the proteome.

PMID- 21736920
TI  - Brain-derived neurotrophic factor enhances the hippocampal expression of key
      postsynaptic proteins in vivo including the monocarboxylate transporter MCT2.
AB  - Brain-derived neurotrophic factor (BDNF) promotes synaptic plasticity via an
      enhancement in expression of specific synaptic proteins. Recent results suggest
      that the neuronal monocarboxylate transporter MCT2 is a postsynaptic protein
      critically involved in synaptic plasticity and long-term memory. To investigate
      in vivo whether BDNF can modulate the expression of MCT2 as well as other
      proteins involved in synaptic plasticity, acute injection of BDNF was performed
      in mouse dorsal hippocampal CA1 area. Using immunohistochemistry, it was found
      that MCT2 expression was enhanced in part of the CA1 area and in the dentate
      gyrus 6 h after a single intrahippocampal injection of BDNF. Similarly,
      expression of the immediate early genes Arc and Zif268 was enhanced in the same
      hippocampal areas, in accordance with their role in synaptic plasticity.
      Immunoblot analysis confirmed the significant enhancement in MCT2 protein
      expression. In contrast, no changes were observed for the glial monocarboxylate
      transporters MCT1 and MCT4. When other synaptic proteins were investigated, it
      was found that postsynaptic density 95 (PSD95) and glutamate receptor 2 (GluR2)
      protein levels were significantly enhanced while no effect could be detected for
      synaptophysin, synaptosomal-associated protein 25 (SNAP25), alphaCaMKII and
      GluR1. These results demonstrate that MCT2 expression can be upregulated together
      with other key postsynaptic proteins in vivo under conditions related to synaptic
      plasticity, further suggesting the importance of energetics for memory formation.

PMID- 21736921
TI  - Glyceraldehyde-3-phosphate dehydrogenase: activity inhibition and protein
      overexpression in rotenone models for Parkinson's disease.
AB  - Rotenone, a widely used pesticide and an environmental risk factor for
      Parkinson's disease (PD), induces nigrostriatal injury, Lewy body-like
      inclusions, and Parkinsonian symptoms in rat models for PD. Our previous data
      indicated that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) overexpression
      and glycolytic inhibition were co-current in rotenone-induced PC12 (rat adrenal
      pheochromocytoma cells) cell death. However, whether GAPDH overexpression plays
      any role in dopaminergic neurodegeneration in vivo remains unknown. In this
      study, we have found that GAPDH overexpression and GAPDH-positive Lewy body-like
      aggregates in nigral dopaminergic neurons while nigral GAPDH glycolytic activity
      decreases in rotenone-based PD animal models. Furthermore, GAPDH knockdown
      reduces rotenone toxicity significantly in PC12. These in vitro and in vivo data
      suggest that GAPDH contributes to the pathogenesis of Parkinson's disease,
      possibly representing a new molecular target for neuroprotective strategies and
      alternative therapies for PD.

PMID- 21736922
TI  - Central neural responses to restraint stress are altered in rats with an early
      life history of repeated brief maternal separation.
AB  - Repeated brief maternal separation (i.e. 15 min daily, MS15) of rat pups during
      the first one to two postnatal weeks enhances active maternal care received by
      the pups and attenuates their later behavioral and neuroendocrine responses to
      stress. In previous work, we found that MS15 also alters the developmental
      assembly and later structure of central neural circuits that control autonomic
      outflow to the viscera, suggesting that MS15 may alter central visceral circuit
      responses to stress. To examine this, juvenile rats with a developmental history
      of either MS15 or no separation (NS) received microinjection of retrograde neural
      tracer, FluoroGold (FG), into the hindbrain dorsal vagal complex (DVC). After 1
      week, FG-injected rats and surgically intact littermates were exposed to either a
      15-min restraint stress or an unrestrained control condition, and then perfused 1
      h later. Brain tissue sections from surgically intact littermates were processed
      for Fos alone or in combination with phenotypic markers to examine stress-induced
      activation of neurons within the paraventricular nucleus of the hypothalamus
      (PVN), bed nucleus of the stria terminalis (BNST), and hindbrain DVC. Compared to
      NS controls, MS15 rats displayed less restraint-induced Fos activation within the
      dorsolateral BNST (dBNST), the caudal PVN, and noradrenergic neurons within the
      caudal DVC. To examine whether these differences corresponded with altered neural
      inputs to the DVC, sections from tracer-injected rats were double-labeled for FG
      and Fos to quantify retrogradely labeled neurons within hypothalamic and limbic
      forebrain regions of interest, and the proportion of these neurons activated
      after restraint. Only the dBNST displayed a significant effect of postnatal
      experience on restraint-induced Fos activation of DVC-projecting neurons. The
      distinct regional effects of MS15 on stress-induced recruitment of neurons within
      hypothalamic, limbic forebrain, and hindbrain regions has interesting
      implications for understanding how early life experience shapes the functional
      organization of stress-responsive circuits.

PMID- 21736923
TI  - Progesterone attenuates demyelination and microglial reaction in the lysolecithin
      injured spinal cord.
AB  - Progesterone treatment of mice with experimental autoimmune encephalomyelitis has
      shown beneficial effects in the spinal cord according to enhanced clinical,
      myelin and neuronal-related parameters. In the present work, we report
      progesterone effects in a model of primary demyelination induced by the
      intraspinal injection of lysophospatidylcholine (LPC). C57Bl6 adult male mice
      remained steroid-untreated or received a single 100 mg progesterone implant,
      which increased circulating steroid levels to those of mouse pregnancy. Seven
      days afterwards mice received a single injection of 1% LPC into the dorsal
      funiculus of the spinal cord. A week after, anesthetized mice were perfused and
      paraffin embedded sections of the spinal cord stained for total myelin using
      Luxol Fast Blue (LFB) histochemistry, for myelin basic protein (MBP)
      immunohistochemistry and for determination of OX-42+ microglia/macrophages.
      Cryostat sections were also prepared and stained for oligodendrocyte precursors
      (NG2+ cells) and mature oligodendrocytes (CC1+ cells). A third batch of spinal
      cords was prepared for analysis of the microglial marker CD11b mRNA using qPCR.
      Results showed that progesterone pretreatment of LPC-injected mice decreased by
      50% the area of demyelination, evaluated by either LFB staining or MBP
      immunostaining, increased the density of NG2+ cells and of mature, CC1+
      oligodendrocytes and decreased the number of OX-42+ cells, respect of steroid
      untreated LPC mice. CD11b mRNA was hyperexpressed in LPC-treated mice, but
      significantly reduced in LPC-mice receiving progesterone. These results indicated
      that progesterone antagonized LPC injury, an effect involving (a) increased
      myelination; (b) stimulation of oligodendrocyte precursors and mature
      oligodendrocytes, and (c) attenuation of the microglial/macrophage response.
      Thus, use of a focal demyelination model suggests that progesterone exerts
      promyelinating and anti-inflammatory effects at the spinal cord level.

PMID- 21736924
TI  - Cholinergic modulation on spike timing-dependent plasticity in hippocampal CA1
      network.
AB  - Cholinergic inputs from the medial septum are projected to pyramidal neurons in
      the hippocampal CA1 region and release acetylcholine (ACh) from their terminals.
      The cholinergic inputs are considered to be integrated with sensory inputs and to
      play a crucial role in learning and memory. Meanwhile, it has been reported that
      the relative timing between pre- and post-synaptic spiking determines the
      direction and extent of synaptic changes in a critical temporal window, a process
      known as spike timing-dependent plasticity (STDP). Positive timing where
      excitatory postsynaptic potential (EPSP) precedes the postsynaptic action
      potential induces long-term potentiation (LTP) while negative timing where EPSP
      follows the action potential induces long-term depression (LTD). To investigate
      the influence of muscarinic activation by cholinergic inputs on synaptic
      plasticity, STDP-inducing stimuli were applied during the muscarinic induction of
      a slow EPSP followed by repetitive stimulation in the stratum oriens. As a
      result, LTP was facilitated and LTD was abolished by the muscarinic activation.
      Furthermore, interestingly, LTP was also facilitated and LTD was switched to LTP
      with an increase in ACh concentration following application of the cholinesterase
      inhibitor eserine. These results indicate that the orientation of plasticity was
      shifted for potentiation by muscarinic activation. On the other hand, the
      application of excess ACh concentration completely suppressed STDP, LTP and LTD.
      In addition, STDP was suppressed in the presence of atropine, a muscarinic ACh
      receptor antagonist. Taken together, the findings suggest that synaptic
      plasticity modulation depends on the amount of cholinergic inputs. The modulation
      of synaptic plasticity by muscarinic activation might be an important stage in
      the integration of top-down and bottom-up information in hippocampal CA1 neurons.

PMID- 21736925
TI  - SynGAP moves out of the core of the postsynaptic density upon depolarization.
AB  - SynGAP is a Ras GTPase activating protein present at the postsynaptic density
      (PSD) in quantities matching those of the core scaffold protein PSD-95. SynGAP is
      reported to inhibit synaptic accumulation of AMPA receptors. Here, we
      characterize by immunogold electron microscopy the distribution of SynGAP at the
      PSD under basal and depolarizing conditions in rat hippocampal neuronal cultures.
      The PSD core, extending up to 40 nm from the postsynaptic membrane, typically
      shows label for SynGAP, while half of the synapses exhibit additional labeling in
      a zone 40-120 nm from the postsynaptic membrane. Upon depolarization with high
      K(+), labeling for SynGAP significantly decreases at the core of the PSD and
      concomitantly increases at the 40-120 nm zone. Under the same depolarization
      conditions, label for PSD-95, the presumed binding partner of SynGAP, does not
      change its localization at the PSD. Depolarization-induced redistribution of
      SynGAP is reversible and also occurs upon application of N-methyl-d-aspartic acid
      (NMDA). Activity-induced movement of SynGAP could vacate sites in the PSD core
      allowing other elements to bind to these sites, such as transmembrane AMPA
      receptor regulatory proteins (TARPs), and simultaneously facilitate access of
      SynGAP to CaMKII and Ras, elements of a regulatory cascade.

PMID- 21736926
TI  - Influence of the reinforcement magnitude on omission effects.
AB  - Reinforcement Omission Effects (ROEs), indicated by higher rate of responses
      after nonreinforced trials in a partial reinforcement schedule, have been
      interpreted as behavioral transient facilitation after nonreinforcement induced
      by primary frustration, and/or behavioral transient inhibition after
      reinforcement induced by demotivation or temporal control. The size of the ROEs
      should depend directly on the reinforcement magnitude. The present experiment
      aimed to clarify the relationship between reinforcement magnitude and the
      omission effects manipulating the magnitude linked to discriminative stimuli in a
      partial reinforcement FI schedule. The results showed that response rates were
      higher after omission than after reinforcement delivery. Besides, response rates
      were highest immediately after the reinforcement omission of a larger magnitude
      than of a smaller magnitude. These data are interpreted in terms of ROEs multiple
      process behavioral facilitation after nonreinforcement, and behavioral transient
      inhibition after reinforcement.

PMID- 21736927
TI  - Gender differences in landmark learning for virtual navigation: the role of
      distance to a goal.
AB  - We used a new virtual program in two experiments to prepare subjects to perform
      the Morris water task (www.nesplora.com). The subjects were Psychology students;
      they were trained to locate a safe platform amidst the presence of four pinpoint
      landmarks spaced around the edge of the pool (i.e., two landmarks relatively near
      the platform and two landmarks relatively distant away from it). At the end of
      the training phase, we administered one test trial without the platform and
      recorded the amount of time that the students had spent in the platform quadrant.
      In Experiment 1, we conducted the test trial in the presence of one or two of the
      distant landmarks. When only one landmark was present during testing, performance
      fell to chance. However, the men outperformed the women when the two distant
      landmarks were both present. Experiment 2 replicated the previous results and
      extended it by showing that no sex differences exist when the searching process
      is based on the near landmarks. Both the men and the women had similarly good
      performances when the landmarks were present both individually and together. When
      present together, an addition effect was found. Far landmark tests favor
      configural learning processes, whereas near landmark tests favor elemental
      learning. Our findings suggest that other factors in addition to the use of
      directional cues can underlie the sex differences in the spatial learning
      process. Thus, we expand upon previous research in the field.

PMID- 21736928
TI  - Individuality in nest building: do southern masked weaver (Ploceus velatus) males
      vary in their nest-building behaviour?
AB  - We currently have little understanding of how birds know what nest to build and
      what little we do know has been gained largely from investigations of the
      completed structures (morphology of finished nests) or of material selection.
      Here we looked at the behaviours performed by male Southern Masked weaverbirds
      when building their nests. During the two earliest phases of construction
      individual males varied in the direction in which they carried and inserted grass
      into their developing nest, the speed at which they completed phases of nest
      construction and in the frequency with which they dropped grass during weaving.
      Behaviours performed during the initial attachment phase, when grass is being
      secured to a bare branch, were not repeatable within males, whereas during the
      subsequent "ring" phase behaviours tended to be repeatable. Some males were
      biased as to which side of the nest they inserted grass blades and strongly
      lateralized individuals completed phases of nest-building more quickly. The lack
      of repeatability of most nest-building behaviours and the changes in those
      behaviours as males build more nests seems most readily explained by increasing
      dexterity. Further work is required to confirm any role for cognition in these
      experience-dependent changes.

PMID- 21736929
TI  - Effect of iontophoresis on in vitro transdermal absorption of almotriptan.
AB  - The aim of the present work was to characterize the in vitro transdermal
      absorption of almotriptan through pig ear skin. The passive diffusion of
      almotriptan malate and its iontophoretic transport were investigated using
      current densities of 0.25 and 0.50mA/cm(2). In vitro iontophoresis experiments
      were conducted on diffusion cells with an agar bridge without background
      electrolytes in the donor compartment. Although both current densities applied
      produced a statistically significant increment with respect to passive permeation
      of almotriptan (p<0.01), that of 0.50mA/cm(2) proved to be the best experimental
      condition for increasing the transport of almotriptan across the skin. Under
      these experimental conditions, the transdermal flux of the drug increased 411
      fold with respect to passive diffusion, reaching 264+/-24MUg/cm(2)h (mean+/-SD).
      Based on these results, and taking into account the pharmacokinetics of
      almotriptan, therapeutic drug plasma levels for the management of migraine could
      be achieved via transdermal iontophoresis using a reasonably sized (around
      7.2cm(2)) patch.

PMID- 21736930
TI  - Modeling and simulation of compact strength due to particle bonding using a
      hybrid discrete-continuum approach.
AB  - The compaction of powder beds into solid bodies occurs by virtue of the formation
      of inter-particle bonds. The mechanical strength of the compact depends on the
      type of bonding interaction, as well as, the inter-particle contact area created
      in the compression process. A hybrid quasi-continuum computational approach has
      been implemented to study the bonding occurring in compressed granular
      assemblies. The approach resolves the powder bed on the particle level, allowing
      for the tracking of contact area generated by particle deformation and the
      computation of history-dependent inter-particle bonding forces. The magnitude of
      the bonding force is calculated using a synthetically constructed potential
      aiming to mimic the shape of typical molecular-type interactions. The uniaxial
      compaction and subsequent relaxation of powder beds, representative of
      pharmaceutical excipients have been simulated. Due to the bonding occurring
      between the individual particles the compressed beds acquire tensile strength.
      Post-relaxation tensile loading of the compacts is used to quantify the magnitude
      of this tensile strength. To validate the computational results, tablets are
      prepared using a compaction simulator under conditions closely resembling the
      simulated scenarios, where subsequently the tablets are subjected to tensile
      loads until failure. The predicted values for the tablet strength utilizing the
      present methodology capture the general trends exhibited by the experimental
      record.

PMID- 21736931
TI  - Bivalent sequential binding of docetaxel to methyl-beta-cyclodextrin.
AB  - New docetaxel (Dtx) and cyclodextrin (CD) inclusion complexes having improved
      apparent water solubility (up to 9.98mgmL(-1)) were obtained from phase
      solubility diagrams. gamma-CD and SBE-beta-CD offered only poor solubility
      enhancements while considerable increases in apparent solubility were obtained
      with Me-beta-CD (20%, w/w) and HP-beta-CD (40%, w/w) (9.98mgmL(-1) and 7.43mgmL(
      1), respectively). The complexation mechanism between Dtx and Me-beta-CD was
      investigated by circular dichroism spectrometry, two-dimensional (1)H NMR (NOESY)
      in D(2)O, isothermal titration calorimetry (ITC) and molecular docking
      calculations. Circular dichroism and NOESY confirmed the existence of non
      covalent interactions between Dtx and Me-beta-CD and suggested that the tert
      butyl group (C(6)-C(9)) and two aromatic groups (C(24)-C(29) and C(30)-C(35)) of
      Dtx interacted with the Me-beta-CD molecules. The combination of ITC results to
      molecular docking calculations led to the identification of an unconventional
      sequential binding mechanism between Me-beta-CD and Dtx. In this sequential
      binding, a Me-beta-CD molecule first interacted with both tert-butyl and C(30)
      C(35) aromatic groups (K(1): 744M(-1)). Then a second Me-beta-CD molecule
      interacted with the C(24)-C(29) aromatic group (K(2): 202M(-1)). The entropy of
      the first interaction was positive, whereas a negative value of entropy was found
      for the second interaction. The opposite behavior observed for these two sites
      was explained by differences in the hydrophobic contact surface and functional
      group flexibility.

PMID- 21736932
TI  - Transport of saquinavir across human brain-microvascular endothelial cells by
      poly(lactide-co-glycolide) nanoparticles with surface poly-(gamma-glutamic acid).
AB  - Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) with surface poly-(gamma
      glutamic acid) (gamma-PGA) were applied to enhance the transport of saquinavir
      (SQV) across the blood-brain barrier (BBB). PLGA NPs encapsulated SQV and grafted
      with gamma-PGA to form drug carriers (gamma-PGA/SQV-PLGA NPs) for crossing
      through a monolayer of human brain-microvascular endothelial cells (HBMECs)
      regulated with human astrocytes. The results revealed that a lower molecular
      weight of gamma-PGA yielded a higher grafting efficiency of gamma-PGA on PLGA
      NPs. In addition, gamma-PGA with a low molecular weight accelerated the
      dissolution of SQV from gamma-PGA/SQV-PLGA NPs. A higher grafting efficiency
      (more didecyl dimethylammonium bromide) and a lower molecular weight of gamma-PGA
      increased the permeability of SQV across the BBB, in general. When the grafting
      efficiency was 85.2% at 6kDa of gamma-PGA, gamma-PGA/SQV-PLGA NPs reached about 6
      times the permeability of free SQV (the maximal permeability). gamma-PGA could
      also promote the endocytosis of NPs and expression of ornithine decarboxylase by
      HBMECs. gamma-PGA/SQV-PLGA NPs are efficacious nanoparticulate carriers in
      delivering antiretroviral drug across the BBB.

PMID- 21736933
TI  - Integrative transcriptional analysis between human and mouse cancer cells
      provides a common set of transformation associated genes.
AB  - Mouse functional genomics is largely used to investigate relevant aspects of
      mammalian physiology and pathology. To which degree mouse models may offer
      accurate representations of molecular events underlining human diseases such as
      cancer is not yet fully established. Herein we compare gene expression signatures
      between a set of human cancer cell lines (NCI-60 cell collection) and a mouse
      cellular model of oncogenic K-ras dependent transformation in order to identify
      their closeness at the transcriptional level. The results of our integrative and
      comparative analysis show that in both species as compared to normal cells or
      tissues the transformation process involves the activation of a transcriptional
      response. Furthermore, the cellular mouse model of K-ras dependent transformation
      has a good degree of similarity with several human cancer cell lines and in
      particular with cell lines containing oncogenic Ras mutations. Moreover both
      species have similar genetic signatures that are associated to the same altered
      cellular pathways (e.g. Spliceosome and Proteasome) or to deregulation of the
      same genes (e.g. cyclin D1, AHSA1 and HNRNPD) detected in the comparison between
      cancer cells versus normal cells or tissues. In summary, we report one of the
      first in-depth analysis of global gene expression profiles of a K-ras dependent
      mouse cell model of transformation and a large collection of human cancer cells
      as compared to their normal counterparts. Taken together our findings show a
      strong correlation in the transcriptional and pathway alteration responses
      between the two species, therefore validating the use of the mouse model as an
      appropriate tool to investigate human cancer, and indicating that the comparative
      analysis, as described here, offers a useful approach to identify cancer-specific
      gene signatures.

PMID- 21736935
TI  - Aberrant production of soluble co-stimulatory molecules CTLA-4 and CD28 in
      patients with chronic hepatitis B.
AB  - Co-stimulation signals are critical for anti-viral immunity. Here we investigated
      whether there is altered expression and the clinical significance of soluble co
      stimulatory molecules in patients with chronic HBV infection. Serum
      concentrations and ex vivo production of soluble CTLA-4, CD28, CD80 and CD86 were
      analyzed by enzyme-linked immunosorbent assay. Serum sCTLA-4 and sCD28
      concentrations in all chronic HBV patients were significantly higher than
      concentrations in healthy control subjects. Serum sCTLA-4 and sCD28 correlated
      significantly with alanine aminotransferase in all chronic HBV patients. Upon
      mitogen stimulation of peripheral blood mononuclear cells, the percentage
      increases in ex vivo production of sCD28 and sCD80 and the percentage decrease in
      sCTLA-4 release were all significantly lower in chronic HBV patients than those
      in healthy subjects. The aberrant production of soluble co-stimulatory molecules
      should reflect the dysregulation of T cell activation and is related to the
      pathogenesis and severity of chronic HBV infection.

PMID- 21736934
TI  - Umbilical cord blood biomarkers of neurologic injury and the risk of cerebral
      palsy or infant death.
AB  - To evaluate the association between cerebral palsy (CP) or infant death and
      putative cord blood biomarkers of neurologic injury, we performed a nested case
      control secondary analysis of a multicenter randomized trial of magnesium sulfate
      (MgSO(4)) versus placebo to prevent CP or death among offspring of women with
      anticipated delivery from 24 to 31 weeks' gestation. Cases were infants who died
      by 1 year (n=25) or developed CP (n=16), and were matched 1:2 to a control group
      (n=82) that survived without developing CP. Umbilical cord sera concentrations of
      S100B, neuron-specific enolase (NSE) and the total soluble form of the receptor
      for advanced glycation end-products (sRAGE) were measured by ELISA in duplicates.
      Maternal characteristics were similar between the 2 groups. Cases were born at a
      lower gestational age (GA) and had lower birth weight compared with controls.
      There were no differences in concentrations of the three biomarkers and the
      composite outcome of CP or infant death. However, S100B was higher (median 847.3
      vs. 495.7 pg/ml; P=0.03) in infants who had CP and total sRAGE was lower (median
      1259.3 vs. 1813.1 pg/ml; P=0.02) in those who died compared with the control
      group. When corrected for delivery GA and treatment group, both differences lost
      statistical significance. In conclusion, cord blood S100B level may be associated
      with CP, but this association was not significant after controlling for GA and
      MgSO(4) treatment.

PMID- 21736936
TI  - Comment on: "Impaired oligodendroglial development by decabromodiphenyl ether in
      rat offspring after maternal exposure from mid-gestation through lactation".

PMID- 21736937
TI  - Concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA)
      and their associations with human semen quality measurements.
AB  - A total of 256 men were studied to evaluate whether serum concentrations of
      perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) impacted semen
      quality or reproductive hormones. Blood and semen were collected and analyzed for
      perfluorochemicals and reproductive and thyroid hormones. Semen quality was
      assessed using standard clinical methods. Linear and logistic modeling was
      performed with semen profile measurements as outcomes and PFOS and PFOA in semen
      and plasma as explanatory variables. Adjusting for age, abstinence, and tobacco
      use, there was no indication that PFOA or PFOS was significantly associated with
      volume, sperm concentration, percent motility, swim-up motility and
      concentration, and directional motility (a function of motility and modal
      progression). Follicle-stimulating hormone was not associated with either PFOA or
      PFOS. Luteinizing hormone was positively correlated with plasma PFOA and PFOS,
      but not semen PFOS. Important methodological concerns included the lack of
      multiple hormonal measurements necessary to address circadian rhythms.

PMID- 21736938
TI  - Differences in serum levels of CB-153 and p,p'-DDE, and reproductive parameters
      between men living south and north in Norway.
AB  - Arctic is contaminated with persistent organochlorine pollutants (POPs), and
      exposure to these compounds may differ between south and north in Norway. POPs
      may have negative impact on male reproductive characteristics. We compared serum
      levels of the CB-153 and p,p'-DDE in men who were born and had lived most of
      their lifetime south and north (close to or above the Arctic Circle) in Norway.
      We found no geographical differences in levels of CB-153 (south: 50 ng/g lipid
      (mean), north: 59 ng/g lipid; p=0.27) or sperm parameters. However, the levels of
      p,p'-DDE were higher in south than in north (81 ng/g lipid (mean) vs. 66 ng/g
      lipid; p=0.02), as were the levels of total and free testosterone. The FSH levels
      were lowest in south. A strong relationship between the CB-153 and the SHBG
      levels was observed. The regional differences observed for p,p'-DDE, testosterone
      and FSH were not reflected in the semen quality.

PMID- 21736939
TI  - Overexpression of SOD in retina: need for increase in H2O2-detoxifying enzyme in
      same cellular compartment.
AB  - In retinitis pigmentosa (RP), various mutations cause rod photoreceptor cell
      death leading to increased oxygen levels in the outer retina, progressive
      oxidative damage to cones, and gradual loss of cone cell function. We have been
      exploring the potential of overexpressing components of the endogenous
      antioxidant defense system to preserve cone cell function in rd10(+/+) mice, a
      model of RP. rd10(+/+) mice deficient in superoxide dismutase 1 (SOD1) showed
      increased levels of superoxide radicals and carbonyl adducts (a marker of
      oxidative damage) in the retina and more rapid loss of cone function than
      rd10(+/+) mice with normal levels of SOD1. This suggests that SOD1 is an
      important component of the antioxidant defense system of cones, but increased
      expression of SOD1 in rd10(+/+) mice increased oxidative damage and accelerated
      the loss of cone function. Coexpression of SOD1 with glutathione peroxidase 4
      (Gpx4), which like SOD1 is localized in the cytoplasm, but not with catalase
      targeted to the mitochondria, reduced oxidative damage in the retina and
      significantly slowed the loss of cone cell function in rd10(+/+) mice. Gene
      transfer resulting in increased expression of SOD2, but not coexpression of SOD2
      and mitochondrial Gpx4, resulted in high levels of H(2)O(2) in the retina. These
      data suggest that to provide benefit in RP, overexpression of an SOD must be
      combined with expression of a peroxide-detoxifying enzyme in the same cellular
      compartment.

PMID- 21736940
TI  - pH-responsive nanoparticles releasing tenofovir intended for the prevention of
      HIV transmission.
AB  - This study is designed to test the hypothesis that tenofovir (TNF) or tenofovir
      disoproxil fumarate (TDF) loaded nanoparticles (NPs) prepared with a blend of
      poly(lactic-co-glycolic acid) (PLGA) and methacrylic acid copolymer (Eudragit(r)
      S-100, or S-100) are noncytotoxic and exhibit significant pH-responsive release
      of anti-HIV microbicides in the presence of human semen fluid simulant (SFS).
      After NPs preparation by emulsification diffusion, their size, encapsulation
      efficiency (EE%), drug release profile, morphology, and cytotoxicity are
      characterized by dynamic light scattering, spectrophotometry, transmission
      electron microscopy, and cellular viability assay/transepithelial electrical
      resistance measurement, respectively. Cellular uptake was elucidated by
      fluorescence spectroscopy and confocal microscopy. The NPs have an average size
      of 250 nm, maximal EE% of 16.1% and 37.2% for TNF and TDF, respectively. There is
      a 4-fold increase in the drug release rate from the 75% S-100 blend in the
      presence of SFS over 72 h. At a concentration up to 10mg/ml, the PLGA/S-100 NPs
      are noncytotoxic for 48 h to vaginal endocervical/epithelial cells and
      Lactobacillus crispatus. The particle uptake (~ 50% in 24h) by these vaginal cell
      lines mostly occurred through caveolin-mediated pathway. These data suggest the
      promise of using PLGA/S-100 NPs as an alternative controlled drug delivery system
      in intravaginal delivery of an anti-HIV/AIDS microbicide.

PMID- 21736941
TI  - Nerve conduits based on immobilization of nerve growth factor onto modified
      chitosan by using genipin as a crosslinking agent.
AB  - Incorporation of nerve growth factor (NGF) into a nerve conduit can improve
      peripheral nerve regeneration. Here, genipin, a natural and low toxic agent, was
      used to crosslink chitosan, a natural polysaccharide, and concurrently to
      immobilize NGF onto modified chitosan, followed by fabrication of chitosan (CS)
      genipin (GP)-NGF nerve conduits. MTT test showed that the cell viability of
      Schwann cells cultured in the conduit extract was not significantly different
      from that in plain medium. The neurite outgrowth measurement and
      immunocytochemistry with anti-growth-associated protein-43 and anti-neurofilament
      indicated that NGF released from CS-GP-NGF nerve conduits retained the
      bioactivity of stimulating neuronal differentiation of PC12 cells. Fracture
      strength measurements and vitamin B12 release analysis confirmed that CS-GP-NGF
      nerve conduits possessed good mechanical properties and adequate permeability. We
      also investigated the in vitro release kinetics of NGF from CS-GP-NGF nerve
      conduits by ELISA. The continuous release profile of NGF, within a 60-day time
      span, consisted of an initial burst that was controlled by a concentration
      gradient-driven diffusion, followed by a zero-order release that was controlled
      by a degradation of chitosan matrix. Collectively, CS-GP-NGF nerve conduits had
      an integrated system for continuous release of NGF, thus holding promise for
      peripheral nerve repair applications.

PMID- 21736942
TI  - Transcriptome and gene expression profile of ovarian follicle tissue of the
      triatomine bug Rhodnius prolixus.
AB  - Insect oocytes grow in close association with the ovarian follicular epithelium
      (OFE), which escorts the oocyte during oogenesis and is responsible for synthesis
      and secretion of the eggshell. We describe a transcriptome of OFE of the
      triatomine bug Rhodnius prolixus, a vector of Chagas disease, to increase our
      knowledge of the role of FE in egg development. Random clones were sequenced from
      a cDNA library of different stages of follicle development. The transcriptome
      showed high commitment to transcription, protein synthesis, and secretion. The
      most abundant cDNA was a secreted (S) small, proline-rich protein with maximal
      expression in the vitellogenic follicle, suggesting a role in oocyte maturation.
      We also found Rp45, a chorion protein already described, and a putative chitin
      associated cuticle protein that was an eggshell component candidate. Six
      transcripts coding for proteins related to the unfolded-protein response (UPR) by
      were chosen and their expression analyzed. Surprisingly, transcripts related to
      UPR showed higher expression during early stages of development and
      downregulation during late stages, when transcripts coding for S proteins
      participating in chorion formation were highly expressed. Several transcripts
      with potential roles in oogenesis and embryo development are also discussed. We
      propose that intense protein synthesis at the FE results in reticulum stress (RS)
      and that lowering expression of a set of genes related to cell survival should
      lead to degeneration of follicular cells at oocyte maturation. This paradoxical
      suppression of UPR suggests that ovarian follicles may represent an interesting
      model for studying control of RS and cell survival in professional S cell types.

PMID- 21736943
TI  - Antibody purification-independent microarrays (PIM) by direct bacteria spotting
      on TiO2-treated slides.
AB  - The preparation of effective conventional antibody microarrays depends on the
      availability of high quality material and on the correct accessibility of the
      antibody active moieties following their immobilization on the support slide. We
      show that spotting bacteria that expose recombinant antibodies on their external
      surface directly on nanostructured-TiO(2) or epoxy slides (purification
      independent microarray - PIM) is a simple and reliable alternative for preparing
      sensitive and specific microarrays for antigen detection. Variable domains of
      single heavy-chain antibodies (VHHs) against fibroblast growth factor receptor 1
      (FGFR1) were used to capture the antigen diluted in serum or BSA solution. The
      FGFR1 detection was performed by either direct antigen labeling or using a
      sandwich system in which FGFR1 was first bound to its antibody and successively
      identified using a labeled FGF. In both cases the signal distribution within each
      spot was uniform and spot morphology regular. The signal-to-noise ratio of the
      signal was extremely elevated and the specificity of the system was proved
      statistically. The LOD of the system for the antigen was calculated being
      0.4ng/mL and the dynamic range between 0.4ng/mL and 10MUg/mL. The microarrays
      prepared with bacteria exposing antibodies remain fully functional for at least
      31 days after spotting. We finally demonstrated that the method is suitable for
      other antigen-antibody pairs and expect that it could be easily adapted to
      further applications such as the display of scFv and IgG antibodies or the
      autoantibody detection using protein PIMs.

PMID- 21736944
TI  - Subchondral bone changes in three different canine models of osteoarthritis.
AB  - OBJECTIVE: To test the hypothesis that changes in subchondral bone are
      significantly different among three canine models of osteoarthritis (OA). DESIGN:
      In 21 purpose-bred mongrel dogs, OA was induced in one knee joint via either
      anterior cruciate ligament transection (ACLt; n = 5), medial femoral condylar
      groove creation (GR; n = 6), or medial meniscal release (MR; n = 5). Five dogs
      that had sham surgery (SH; n = 5) in one knee joint served as controls. Lameness
      scoring was performed every 4 weeks. Twelve weeks after surgery, the knee joints
      were examined by histology and histomorphometry. RESULTS: Articular cartilage
      pathology as determined by Mankin scores was significantly severe in all three OA
      models compared to SH controls in the medial tibia (P < 0.001 to P = 0.026). ACLt
      had significantly thinner subchondral plate thickness (Sp.Th) in both the medial
      and lateral tibias while MR had significantly thicker Sp.Th in the medial tibia
      compared to SH controls (P < 0.001 to P = 0.011). Trabecular bone volume (BV/TV)
      and trabecular bone thickness (Tb.Th) for ACLt were significantly less than SH
      controls in the tibias (P < 0.001 to P = 0.011). Tibial Sp.Th, BV/TV, and Tb.Th
      were all moderately to strongly correlated with lameness scores obtained
      throughout the study period (r = -0.436 to r = -0.738, P < 0.001 to P = 0.047)
      while Mankin scores showed moderate to strong correlations with Sp.Th in each OA
      model (r = 0.465 to r = 0.816, P < 0.001 to P = 0.033). CONCLUSIONS: Changes in
      Sp.Th are associated with articular cartilage damage while tibial Sp.Th and BV/TV
      and Tb.Th appear to be all influenced by joint loading alterations.

PMID- 21736945
TI  - Glucocorticoids are required for extinction of predator stress-induced
      hyperarousal.
AB  - BACKGROUND: The role of glucocorticoids in extinction of traumatic memories has
      not been fully characterized despite its potential as a therapeutic target for
      acquired posttraumatic stress disorder (PTSD). The predator stress paradigm
      allows us to determine whether glucocorticoids mediate the extinction of both
      context-dependent and context-independent fear memories. METHODS: Male C57BL/6J
      mice were exposed to a predator (cat) then repeatedly exposed to the predator
      stress context in the absence of the cat. Context-dependent (associative) fear
      memory was assessed as suppression of activity during re-exposure to the predator
      stress context without the cat (extinction trials). Context-independent fear (non
      associative) was assessed seven days after extinction trials using measures of
      hyperarousal and anxiety-like behaviours in environments unlike the predator
      stress context. To assess the role of glucocorticoids, mice were injected with
      metyrapone (50mg/kg) 90 min prior to extinction trials in predator stressed mice
      and context-dependent and context-independent fear memories were assessed.
      Finally, metyrapone-treated predator stressed mice were injected with
      corticosterone (5 or 10mg/kg) immediately following extinction trials and context
      dependent and context-independent fear memories were assessed. RESULTS: Repeated
      re-exposure to the predator stress context without the cat present extinguished
      context-dependent fear memory, and also reduced hyperarousal, a generalized,
      chronic PTSD-like symptom. We show that extinction of context-independent
      predator stress-induced hyperarousal is dependent on endogenous glucocorticoids
      during the extinction trials. Furthermore, the inhibition of extinction by
      metyrapone on startle amplitude was reduced by exogenous administration of
      corticosterone following extinction trials. Overall, these data implicate
      glucocorticoids in the extinction of hyperarousal, a core symptom of PTSD.

PMID- 21736946
TI  - Nitric oxide production by a murine macrophage cell line (RAW264.7 cells)
      stimulated with Aggregatibacter actinomycetemcomitans surface-associated
      material.
AB  - Nitric oxide (NO) may play a crucial role in the pathogenesis of periodontal
      disease and, hence, the aim of the present study was to test the hypothesis that
      Aggregatibacter actinomycetemcomitans surface-associated material (SAM)
      stimulates inducible nitric oxide synthase (iNOS) activity and NO production by
      the murine macrophage cell line RAW264.7. Cells were stimulated with untreated or
      heat-treated A. actinomycetemcomitans SAM and with or without pre-treatment with
      L-N(6)-(1-Iminoethyl)-lysine (L-NIL) (an iNOS inhibitor), polymyxin B, interferon
      gamma (IFN-gamma) and Interleukin-4 (IL-4), IL-10, genistein [a protein tyrosine
      kinase (PTK) inhibitor], bisindolylmaleimide [a protein kinase C (PKC)
      inhibitor], bromophenacyl bromide (BPB) [a phospholipase A(2) (PLA2) inhibitor]
      or wortmannin [phosphatidylinositol 3-kinase (PI-3K) inhibitor]. The iNOS
      activity and nitrite production in the cell cultures were determined. Untreated
      but not heat-treated A. actinomycetemcomitans SAM-stimulated both iNOS activity
      and nitrite production in RAW264.7 cells. L-NIL, IL-4, IL-10, genistein,
      bisindolylmaleimide, or BPB, suppressed but IFN-gamma enhanced both iNOS activity
      and nitrite production by A. actinomycetemcomitans SAM-stimulated cells.
      Wortmannin and polymyxin B failed to alter both iNOS activity or nitrite
      production by A. actinomycetemcomitans SAM treated cells. Therefore, the present
      study suggests that a heat-sensitive protein constituent(s) of A.
      actinomycetemcomitans SAM stimulates both iNOS activity and nitrite production by
      RAW264.7 cells in a cytokine, PTK, PKC, and PLA(2) but not PI-3K-dependent
      fashion.

PMID- 21736947
TI  - Polarity and the diversity of growth mechanisms in bacteria.
AB  - Bacterial cell growth is a complex process consisting of two distinct phases:
      cell elongation and septum formation prior to cell division. Although bacteria
      have evolved several different mechanisms for cell growth, it is clear that tight
      spatial and temporal regulation of peptidoglycan synthesis is a common theme. In
      this review, we discuss bacterial cell growth with a particular emphasis on
      bacteria that utilize tip extension as a mechanism for cell elongation. We
      describe polar growth among diverse bacteria and consider the advantages and
      consequences of this mode of cell elongation.

PMID- 21736948
TI  - The SALM/Lrfn family of leucine-rich repeat-containing cell adhesion molecules.
AB  - Synaptic adhesion molecules play important roles in various stages of neuronal
      development, including neurite outgrowth and synapse formation. The SALM
      (synaptic adhesion-like molecule) family of adhesion molecules, also known as
      Lrfn, belongs to the superfamily of leucine-rich repeat (LRR)-containing adhesion
      molecules. Proteins of the SALM family, which includes five known members (SALMs
      1-5), have been implicated in the regulation of neurite outgrowth and branching,
      and synapse formation and maturation. Despite sharing a similar domain structure,
      individual SALM family proteins appear to have distinct functions. SALMs 1-3
      contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant
      postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. SALM1
      directly interacts with NMDA receptors but not with AMPA receptors, whereas SALM2
      associates with both NMDA and AMPA receptors. SALMs 1-3 form homo- and
      heteromeric complexes with each other in a cis manner, whereas SALM4 and SALM5 do
      not, but instead participate in homophilic, trans-cellular adhesion. SALM3 and
      SALM5, but not other SALMs, possess synaptogenic activity, inducing presynaptic
      differentiation in contacting axons. All SALMs promote neurite outgrowth, while
      SALM4 uniquely increases the number of primary processes extending from the cell
      body. In addition to these functional diversities, the fifth member of the SALM
      family, SALM5/Lrfn5, has recently been implicated in severe progressive autism
      and familial schizophrenia, pointing to the clinical importance of SALMs.

PMID- 21736950
TI  - Thermal energetics and torpor in the common pipistrelle bat, Pipistrellus
      pipistrellus (Vespertilionidae: Mammalia).
AB  - Rate of metabolism and body temperature were studied between -6 degrees C and 38
      degrees C in the common pipistrelle bat Pipistrellus pipistrellus
      (Vespertilionidae), a European species lying close to the lower end of the
      mammalian size range (body mass 4.9+/-0.8g, N=28). Individuals maintained only
      occasionally a normothermic body temperature averaging 35.4+/-1.1 degrees C (N=4)
      and often showed torpor during metabolic runs. The thermoneutral zone was found
      above 33 degrees C, and basal rate of metabolism averaged 7.6+/-0.8mL O(2)h(-1)
      (N=28), which is 69% of the value predicted on the basis of body mass. Minimal
      wet thermal conductance was 161% of the expected value. During torpor, the rate
      of metabolism was related exponentially to body temperature with a Q(10) value of
      2.57. Torpid bats showed intermittent ventilation, with the frequency of
      ventilatory cycles increasing exponentially with body temperature. Basal rate of
      metabolism (BMR) varied significantly with season and body temperature, but not
      with body mass. It was lower before the hibernation period than during the
      summer. The patterns observed are generally consistent with those exhibited by
      other vespertilionids of temperate regions. However, divergences occur with
      previous measurements on European pipistrelles, and the causes of the seasonal
      variation in BMR, which has only rarely been searched for among vespertilionids,
      remain to be examined.

PMID- 21736951
TI  - Genetic polymorphisms of GSTM1, GSTT1 and GSTP1 and susceptibility to DNA damage
      in workers occupationally exposed to organophosphate pesticides.
AB  - GSTM1, T1 and P1 are important enzymes of glutathione S-transferases (GSTs),
      involved in the metabolism of many endogenous and exogenous compounds. Individual
      genetic variation in these metabolizing enzymes may influence the metabolism of
      their substrates. The present study was designed to determine the genotoxic
      effects using DNA damage and its association with GSTM1, GSTT1, and GSTP1
      (Ile105Val) genetic polymorphisms in workers occupationally exposed to
      organophosphate pesticides (OPs). We examined 230 subjects including 115 workers
      occupationally exposed to OPs and an equal number of normal healthy controls. The
      DNA damage was evaluated using the alkaline comet assay and genotyping was done
      using individual PCR or PCR-RFLP. Significantly higher DNA tail moment (TM) was
      observed in workers as compared to control subjects (14.41 +/- 2.25 vs. 6.36 +/-
      1.41 tail % DNA, p<0.001). The results revealed significantly higher DNA TM in
      workers with GSTM1 null genotype than those with GSTM1 positive (15.18 vs. 14.15
      tail % DNA, p=0.03). A significantly higher DNA TM was also observed in workers
      with homozygous Ile-Ile GSTP1 genotype than heterozygous (Ile-Val) and mutant
      (Val-Val) GSTP1 genotype (p=0.02). In conclusion, the results show that null
      deletion of GSTM1 and homozygote wild GSTP1 genotype could be related to inter
      individual differences in DNA damage arises from the gene-environment
      interactions in workers occupationally exposed to OPs.

PMID- 21736949
TI  - The neuronal control of cardiac functions in Molluscs.
AB  - In this manuscript, I review the current and relevant classical studies on
      properties of the Mollusca heart and their central nervous system including
      ganglia, neurons, and nerves involved in cardiomodulation. Similar to mammalian
      brain hemispheres, these invertebrates possess symmetrical pairs of ganglia
      albeit visceral (only one) ganglion and the parietal ganglia (the right ganglion
      is bigger than the left one). Furthermore, there are two major regulatory drives
      into the compartments (pericard, auricle, and ventricle) and cardiomyocytes of
      the heart. These are the excitatory and inhibitory signals that originate from a
      few designated neurons and their putative neurotransmitters. Many of these
      neurons are well-identified, their specific locations within the corresponding
      ganglion are mapped, and some are termed as either heart excitatory (HE) or
      inhibitory (HI) cells. The remaining neurons are classified as cardio-regulatory,
      and their direct and indirect actions on the heart's function have been
      documented. The cardiovascular anatomy of frequently used experimental animals,
      Achatina, Aplysia, Helix, and Lymnaea is relatively simple. However, as in
      humans, it possesses all major components including even trabeculae and atrio
      ventricular valves. Since the myocardial cells are enzymatically dispersible,
      multiple voltage dependent cationic currents in isolated cardiomyocytes are
      described. The latter include at least the A-type K(+), delayed rectifier K(+),
      TTX-sensitive Na(+), and L-type Ca(2+) channels.

PMID- 21736952
TI  - Inhibition by wheat sprout (Triticum aestivum) juice of bisphenol A-induced
      oxidative stress in young women.
AB  - For health of future generation, fertile young women should be monitored for
      exposure of endocrine disrupting chemicals (EDCs). Among EDCs, bisphenol A (BPA)
      is suggested to induce reactive oxygen species (ROS) which play an important role
      in pathologies of female diseases such as endometriosis. On the other hand,
      previous studies suggested that sprouts of wheat (Triticum aestivum) have
      antimutagenicity and antioxidant activity. We performed the 2 weeks intervention
      of wheat sprout juice (100ml/day) to investigate its effects on BPA-exposure and 
      oxidative toxicity in young women (N=14, age=24.4+/-4.0). Geometrical mean of
      urinary BPA levels was 1.81 (GSTD, 4.34)MUg/g creatinine. We observed that
      irregular meals significantly increased levels of urinary BPA approximate 3 times
      (p=0.03). In addition, we found BPA-induced oxidative stress is correlated with
      levels of 8-hydroxydeoxyguanosine (8-OHdG) or malondialdehyde (MDA) levels
      (p=0.18 or 0.03, respectively). We also observed a continuous reduction of
      urinary BPA during the wheat sprout intervention (p=0.02). In summary, our data
      suggested potential detoxification of wheat sprouts on BPA-toxicity via
      antioxidative and interference of absorption, distribution, metabolism and
      excretion (ADME)-mediated mechanisms in young women.

PMID- 21736954
TI  - Involvement of CTP:phosphocholine cytidylyltransferase-beta2 in axonal
      phosphatidylcholine synthesis and branching of neurons.
AB  - In the brain, phosphatidylcholine (PC) is synthesized by the CDP-choline pathway
      in which the rate-limiting step is catalyzed by two isoforms of
      CTP:phosphocholine cytidylyltransferase (CT): CTalpha and CTbeta2. In mice,
      CTbeta2 mRNA is more highly expressed in the brain than in other tissues, and
      several observations suggest that CTbeta2 plays an important role in the nervous
      system. We, therefore, investigated the importance of CTbeta2 for PC synthesis as
      well as for axon formation, growth and branching of primary sympathetic neurons.
      We show that in cultured primary neurons nerve growth factor increases the amount
      of CTbeta2, but not CTalpha, mRNA and protein. The brains of mice lacking CTbeta2
      had normal PC content despite having 35% lower CT activity than wild-type brains.
      CTbeta2 mRNA and protein are abundant in distal axons of mouse sympathetic
      neurons whereas CTalpha mRNA and protein were not detected. Moreover, CTbeta2
      deficiency in distal axons reduced the incorporation of [(3)H]choline into PC by
      95% whereas PC synthesis in cell bodies/proximal axons was unaltered. These data
      suggest that CTbeta2 is the major CT isoform involved in PC synthesis in axons.
      Axons of CTbeta2-deficient sympathetic neurons contained 32% fewer branch points
      than did wild-type neurons although the number of axons/neuron and the rate of
      axon extension were the same as in wild-type neurons. We conclude that in distal
      axons of primary sympathetic neurons CTbeta2 is a major contributor to PC
      synthesis and promotes axon branching, whereas CTalpha appears to be the major CT
      isoform involved in PC synthesis in cell bodies/proximal axons.

PMID- 21736955
TI  - Workshop and panel discussion: high-throughput cryopreservation of germplasm as
      an exchange currency for genetic resources.

PMID- 21736953
TI  - Role of plasma phospholipid transfer protein in lipid and lipoprotein metabolism.
AB  - The understanding of the physiological and pathophysiological role of PLTP has
      greatly increased since the discovery of PLTP more than a quarter of century ago.
      A comprehensive review of PLTP is presented on the following topics: PLTP gene
      organization and structure; PLTP transfer properties; different forms of PLTP;
      characteristics of plasma PLTP complexes; relationship of plasma PLTP activity,
      mass and specific activity with lipoprotein and metabolic factors; role of PLTP
      in lipoprotein metabolism; PLTP and reverse cholesterol transport; insights from
      studies of PLTP variants; insights of PLTP from animal studies; PLTP and
      atherosclerosis; PLTP and signal transduction; PLTP in the brain; and PLTP in
      human disease. PLTP's central role in lipoprotein metabolism and lipid transport
      in the vascular compartment has been firmly established. However, more studies
      are needed to further delineate PLTP's functions in specific tissues, such as the
      lung, brain and adipose tissue. Furthermore, the specific role that PLTP plays in
      human diseases, such as atherosclerosis, cancer, or neurodegenerative disease,
      remains to be clarified. Exciting directions for future research include
      evaluation of PLTP's physiological relevance in intracellular lipid metabolism
      and signal transduction, which undoubtedly will advance our knowledge of PLTP
      functions in health and disease. This article is part of a Special Issue entitled
      Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John
      F. Oram (1945-2010).

PMID- 21736956
TI  - Cell delivery in cardiac regenerative therapy.
AB  - There is a growing interest in the clinical application of stem cells as a novel
      therapeutic approach for treatment of myocardial infarction and prevention of
      subsequent heart failure. Transplanted stem cells improve cardiac functions
      through multiple mechanisms, which include but are not limited to promoting
      angiogenesis, replacing dead cardiomyocytes, modulating cardiac remodeling. Most
      of the results obtained so far are exciting and very promising, spawning an
      increasing number of clinical trials recently. However, many problems still
      remain to be resolved such as the best delivery method for transplantation of
      cells to the injured myocardium and the issue of how to optimize the delivery of
      targeted cells is of exceptional clinical relevance. In this review, we focus on
      the different delivery strategies in cardiac regenerative therapy, as well as
      provide a brief overview of current clinical trials utilizing cell-based therapy
      in patients with ischemic heart disease.

PMID- 21736957
TI  - Kinetics of plasma SPB and RAGE during mechanical ventilation in patients
      undergoing major vascular surgery.
AB  - Receptor-of-Advanced-Glycation-End-products (RAGE) and Surfactant-Protein-type-B
      (SPB) are reported as lung injury markers. Unlike SPB, RAGE is secreted by
      several tissues, so that RAGE specificity as lung injury marker is questionable.
      We measured SPB and RAGE in 19 patients undergoing major vascular abdominal
      surgery. SPB and RAGE were measured before mechanical ventilation (T0), at 1st
      (T1), 2nd (T2) and, when present, 3rd (T3) hour of mechanical ventilation, and 1h
      after extubation (T(POST)). Last data during mechanical ventilation, either T2 or
      T3, are reported as T(END). SPB and RAGE values were normalized for total protein
      (SPB(N) and RAGE(N)). SPB(N) and RAGE(N) increments from T0 to T(END) were 56.2
      [39.1] ng/mg (mean [75-25 percentile]) and 10.6[7.1] pg/mg, respectively. SPB
      values increased progressively during mechanical ventilation, whereas RAGE values
      increased at T(1) but not thereafter. SPB(N) increase (T(END)-T0), but not
      RAGE(N), was related to DeltaPaO(2)/FiO2 changes during mechanical ventilation
      (r=0.575, p=0.01). Plasma RAGE(N) and SPB(N) kinetics in patients undergoing
      major vascular surgery are different.

PMID- 21736958
TI  - Prenatal hyperoxia blunts the hypoxic ventilatory chemosensitivity of the 1-day
      old chicken hatchling.
AB  - Hypoxia sustained during the prenatal period lowers the ventilatory (V(E))
      response to hypoxia of the newborn. This phenomenon probably results from a
      disturbance in the normal development of the peripheral chemoreceptors, as shown
      to be the case postnatally after sustained period of low or high oxygen. To test
      the possibility that prolonged prenatal hyperoxia may have a similar effect, the
      breathing pattern and the V(E) responses to hypoxia or hypercapnia were measured
      by a modification of the barometric technique in 1-day old chicken hatchlings
      exposed to 40% O2 or 60% O2 (N=16 each) during the last week of incubation
      (hatching included), and in controls incubated in normoxia (N=16). During air
      breathing and moderate hypoxia (15% O2), neither group differed from controls.
      However, the V(E) response to 10% O2 was reduced to less than half normal in both
      groups of prenatal-hyperoxia hatchlings. The hypoxic drop in oxygen consumption
      V(O2) was more marked than in controls, which probably helped to limit the degree
      of hypoxemia and to sustain the hyperventilation (increase in V(E)-V(O2) ratio).
      The V(E) response to hypercapnia was almost normal, suggesting that there was no
      mechanical limitation on V(E). The degree of blunting in the V(E) response to
      hypoxia was very similar to that previously measured in hatchlings exposed to
      hypoxia during the last week of incubation. The results support to the view that
      sustained changes in oxygenation during the prenatal period reduce the newborn's
      V(E) response to hypoxia probably because of a major dysfunction of the carotid
      bodies.

PMID- 21736959
TI  - A 2 Mb deletion in 14q13 associated with severe developmental delay and
      hemophagocytic lymphohistiocytosis.
AB  - Interstitial deletions of chromosome 14 have rarely been described. We report on
      a boy in whom a 2 Mb deletion in 14q13 was discovered by array CGH. The deletion
      was a de novo event. The boy presented with asymmetrical growth retardation at
      birth. There was severe developmental delay with muscular hypotonia and focal
      epilepsy with apneic episodes progressing to serial tonic seizures. At the age of
      3 3/12 years he was diagnosed with pneumonia. In the further course he developed
      symptoms of hemophagocytic lymphohistiocytosis. He died due to organ failure.
      Herein the clinical findings are compared to patients with cytogenetic visible
      deletions encompassing the region deleted in the proband and the possible
      connection with the deleted genes.

PMID- 21736971
TI  - Featuring Waldo Nelson. Introduction.

PMID- 21736972
TI  - Waldo E. Nelson, MD (1898-1997) giant of pediatrics.

PMID- 21736960
TI  - Mammalian alphaherpesvirus miRNAs.
AB  - Mammalian alphaherpesviruses are major causes of human and veterinary disease.
      During productive infection, these viruses exhibit complex and robust patterns of
      gene expression. These viruses also form latent infections in neurons of sensory
      ganglia in which productive cycle gene expression is highly repressed. Both modes
      of infection provide advantageous opportunities for regulation by microRNAs. Thus
      far, published data regarding microRNAs are available for six mammalian
      alphaherpesviruses. No microRNAs have yet been detected from varicella zoster
      virus. The five other viruses-herpes simplex viruses-1 and -2, herpes B virus,
      bovine herpesvirus-1, and pseudorabies virus-representing both genera of
      mammalian alphaherpesviruses have been shown to express microRNAs. In this
      article, we discuss these microRNAs in terms of where they are encoded in the
      viral genome relative to other viral transcripts; whether they are expressed
      during productive or latent infection; their potential targets; what little is
      known about their actual targets and functions during viral infection; and what
      little is known about the interactions of these viruses with the host microRNA
      machinery. This article is part of a Special Issue entitled: "MicroRNAs in viral
      gene regulation".

PMID- 21736973
TI  - Developing leadership in global child health.

PMID- 21736974
TI  - Update on nutritional recommendations for the pediatric patient.

PMID- 21736975
TI  - Immunization update III.

PMID- 21736976
TI  - The human Parechoviruses: an overview.

PMID- 21736977
TI  - Care of the foster child: a primer for the pediatrician.

PMID- 21736978
TI  - School-based health centers: a model for the provision of adolescent primary
      care.

PMID- 21736979
TI  - The past decade in pediatric education: progress, concerns, and questions.

PMID- 21736980
TI  - Controversies surrounding pediatric psychopharmacology.

PMID- 21736981
TI  - Management of pediatric intestinal failure.

PMID- 21736982
TI  - Infantile hypertrophic pyloric stenosis: epidemiology, genetics, and clinical
      update.

PMID- 21736983
TI  - rhGH safety and efficacy update.

PMID- 21736984
TI  - Update on precocious puberty: girls are showing signs of puberty earlier, but
      most do not require treatment.

PMID- 21736985
TI  - Update on pediatric epilepsy.

PMID- 21736986
TI  - Hearing loss and cochlear implantation in children.

PMID- 21736987
TI  - Neuroblastoma.

PMID- 21736988
TI  - Proceedings of the 8th European Congress of Reproductive Immunology. Preface.

PMID- 21736989
TI  - [The Annales de Pathologie, prefered media for French-speaking pathologists].

PMID- 21736990
TI  - [Publication of the guidelines for hospital molecular genetics platforms of
      cancers].

PMID- 21736991
TI  - [Guidelines for hospital molecular genetics platforms of cancers.Institut
      National du Cancer].

PMID- 21736992
TI  - [Eosinophilic angiocentric fibrosis and granuloma facial with extra facial
      presentation, the same pathology?].
AB  - Eosinophilic angiocentric fibrosis is a rare fibro inflammatory lesion of unknown
      etiology which occurs usually in the upper respiratory tract mucosa of middle
      aged adults. The histologic features show an eosinophilic vasculitis and an
      angiocentric fibrosis with onion-skin pattern. Firstly described as a mucosal
      variant of the granuloma facial, which is a rare cutaneous vasculitis with
      eosinophils, it is considerated by some authors as separated entities. Four cases
      have been described in the orbit and three of them were in fact an extension of a
      sinusal lesion. We report the first case affecting a 69-years-old male patient
      who showed an isolated orbital involvement in association with granuloma facial,
      extra facial. This observation illustrates the relationship between these two
      pathologies and consolidates the first hypothesis of a single disease with
      cutaneous or mucosal involvement.

PMID- 21736993
TI  - [Diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle
      aspiration in mediastinal lymph nodes].
AB  - INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration in
      mediastinal lymph nodes is a safe method that can be performed for mediastinal
      and hilar lymph nodes sampling. Because it allows collecting only a small amount
      of materiel, an optimal processing of the samples is needed. MATERIAL AND
      METHODS: Based on 150 consecutive procedures, we evaluate the overall diagnostic
      performances and of each technical methods used for the exploitation of the
      samples. RESULTS: The global diagnostic yield is 64.0% for the 50 first exams
      (learning phase), 88.0% for the next 100 exams. The maximal sensitivity and
      negative predictive value (NPV) are 79.3%, 96.3% and 92.7%, respectively. The
      yield, sensitivity and NPV of smears are 68.0%, 75.0% and 66.0%, of monolayer
      preparation 77.8%, 62.1% and 50.0%, of sections from tissue cores of 65.8%, 94.4%
      and 86.7%. The combination of the different methods increases the yield comparing
      to tissue cores and smears when taken alone (P < 0.05), and the sensibility and
      the NPV comparing to smears (P < 0.0005 and P < 0.01, respectively) and monolayer
      preparation (P < 0.0001 and P < 0.0005, respectively). The sensitivity of tissue
      cores is greater than smears (P < 0.005) and monolayer preparations (P < 0.0001).
      This increase in sensitivity is significant for granuloma (sarcoidosis), but not
      for carcinoma. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle
      aspiration is an accurate and sensitive technique. Liquid based conditioning of
      samples and paraffin embedded tissue cores increases the diagnostic performances
      comparing to smears, notably for the diagnosis of sarcoidosis.

PMID- 21736994
TI  - [Myxoid mesenchymal tumors of uterus: endometrial stromal and smooth muscle
      tumors, myxoid variant].
AB  - Four myxoid variant of uterine mesenchymal tumors are reported. One was a low
      grade stromal sarcoma with infiltrative margins and the others were well
      circumscribed tumors corresponding to an endometrial stromal nodule and two
      leiomyomas. They were hypocellular neoplasms composed of stellated cells with an
      abundant Alcian Blue positive myxoid matrix. The myxoid nature of the neoplasms
      obscured their cellular nature and made the distinction between smooth muscle and
      endometrial stromal tumors difficult. Endometrial stromal tumors, showed very
      focal areas of small basophilic cells, characteristic of endometrial stroma. The
      diagnosis was based on the presence of a spiral arteriolar network, a CD10
      positivity as well as the absence of h-caldesmon and desmin expression. The two
      myxoid leiomyomas showed more spindle cells and a desmin expression while h
      caldesmon was negative and CD10 focally positive in both cases. Myxoid variant of
      endometrial stromal tumors does not necessarily exhibit the typical morphology of
      endometrial stroma. They may demonstrate morphological features of smooth muscle
      tumors in the uterus. Also, myxoid changes in uterin smooth muscle tumors may
      modify the classical immunoreactivity of smooth muscle markers in these tumors
      and make it difficult to distinguish between benign and malignant neoplasms. An
      immunohistochemical panel of antibodies including CD10, h-caldesmon and desmin
      may help in establishing the correct diagnosis.

PMID- 21736995
TI  - [Cutaneous neutrophils infiltrate. Introduction].

PMID- 21736996
TI  - [Cutaneous neutrophils infiltrates. Case 1. Neutrophilic dermatosis of the dorsal
      hands].

PMID- 21736997
TI  - [Cutaneous neutrophils infiltrates. Case 2. Erythema elevatum diutinum, late
      stage].

PMID- 21736998
TI  - [Cutaneous neutrophils infiltrates. Case 3. Bullous IgA linear dermatosis].

PMID- 21736999
TI  - [Cutaneous neutrophils infiltrates. Case 4. Pseudo-tumoral cutaneous
      alternariosis].

PMID- 21737000
TI  - [Cutaneous neutrophils infiltrates. Case 5. Interstitial granulomatous dermatitis
      (IGD)].

PMID- 21737001
TI  - [Cutaneous neutrophils infiltrates. Case 6. Neutrophilic dermatosis (Sweet
      syndrome) with atypical "blast-like" cells].

PMID- 21737002
TI  - [Cutaneous neutrophils infiltrates. Case 7. Lymphomatoid papulosis].

PMID- 21737003
TI  - [Cutaneous neutrophils infiltrates. Case 8. CINCA/NOMID syndrome].

PMID- 21737004
TI  - [Pharyngeal fibrovascular polyp].
AB  - The giant fibrovascular polyp of the hypopharynx is a rare and benign tumor. We
      report one case in a 46-year-old man. This lesion, usually unique, affects
      predominantly men with an average age of 53 years. These polyps are located
      predominantly in the upper esophagus and rarely in the hypopharynx. They are
      usually asymptomatic and small, detected by endoscopy. They can grow to
      considerable length and cause digestive or respiratory symptoms. Histologically,
      fibrovascular polyps consist of a various mixture of fibrous and lipomatous
      elements with abundant vascularisation and they are covered by normal squamous
      epithelium. The lack of muscular support and the pressure difference in the
      peristaltic wave contribute to polyp formation.

PMID- 21737005
TI  - [Basaloid squamous carcinoma with a spindle cell component and osseous metaplasia
      presenting as a polyp of the hypopharynx].
AB  - We report a case of basaloid squamous carcinoma with a spindle cell component of
      the hypopharynx, in a 61-years-old-man. An excisional biopsy of a pedonculated
      and polypoid tumour was performed by endoscopy. The histologic examination
      revealed a biphasic tumour with both a basaloid carcinomatous and a spindle cell
      component. Focally, osseous metaplasia was seen. The spindle cell component
      demonstrated immunoreactivity with the p63 epithelial marker. The patient was
      treated with chemotherapy followed by radiotherapy. The patient has been free of
      disease for one year. It's the ninth case reported in the literature of a
      biphasic carcinoma with both a basaloid squamous and a spindle cell component and
      the first case with osseous metaplasia.

PMID- 21737006
TI  - [Epithelioid hemangioendothelioma of the inferior vena cava].
AB  - Epithelioid hemangioendothelioma is a rare endothelial cell-derived tumor of
      intermediate grade malignancy. It has an unpredictable outcome, independently of
      the usual histoprognostic criteria. Thirty-three cases with intravascular
      localisation are described in the literature. We describe a case occurring in a
      31-year-old male, which developed an inferior veina cava tumor, with recurrence
      after incomplete surgical resection and chemotherapy. He was operated on again
      under extracorporeal circulation and complete surgical resection was then
      performed. Histologic examination found an intravascular epithelioid
      hemangioendothelioma developing in the vascular lumen without vascular wall
      infiltration. This entity represents a challenge not only for the vascular
      surgeon, but also for the pathologist given its difficult diagnosis.

PMID- 21737007
TI  - [A rare cutaneous congenital sarcoma: plexiform fibrohistiocytic tumor].
AB  - We report the unusual case of a three-year-old girl which presented since birth a
      pigmented tumor of the left side 0.5cm in diameter. Surgical removal was decided
      given the hypothesis of a congenital naevo-cellular naevus. The histological
      study ended with the diagnosis of plexiform fibrohistiocytic tumor (PFHT). Two
      other congenital PFHT have been reported until now. PFHT is a rare mesenchymal
      neoplasm of intermediate malignancy, first reported by Enzinger and Zhang in 1988
      which may be difficult to diagnose, because of its low frequency, particulary in
      congenital cases. It is important to distinguish it from others childhood
      cutaneous tumors (particulary plexiform neurofibroma, cellular neurothekeoma,
      infantile myofibromatosis, and fibrous hamartoma). The tumor has a high local
      recurrence rate and complete surgical resection of the tumor, with wider margins,
      is required.

PMID- 21737008
TI  - [A fatal laryngeal lesion].

PMID- 21737009
TI  - [Peritoneum and ovary--a case report].

PMID- 21737010
TI  - Acute coronary syndrome with unexpected background: rupture of left valsalva
      sinus aneurysm.

PMID- 21737011
TI  - Cardiovascular risk assessment of the liver transplant candidate.
AB  - Liver transplantation (LT) candidates today are increasingly older, have greater
      medical acuity, and have more cardiovascular comorbidities than ever before.
      Steadily rising model for end-stage liver disease (MELD) scores at the time of
      transplant, resulting from high organ demand, reflect the escalating risk
      profiles of LT candidates. In addition to advanced age and the presence of
      comorbidities, there are specific cardiovascular responses in cirrhosis that can
      be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually
      demonstrate increased cardiac output and a compromised ventricular response to
      stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances
      are likely mediated by decreased beta-agonist transduction, increased circulating
      inflammatory mediators with cardiodepressant properties, and repolarization
      changes. Low systemic vascular resistance and bradycardia are also commonly seen
      in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes
      all contribute to the potential for cardiovascular complications, particularly
      with the altered hemodynamic stresses that LT patients face in the immediate post
      operative period. Post-transplant reperfusion may result in cardiac death due to
      a multitude of causes, including arrhythmia, acute heart failure, and myocardial
      infarction. Recognizing the hemodynamic challenges encountered by LT patients in
      the perioperative period and how these responses can be exacerbated by underlying
      cardiac pathology is critical in developing recommendations for the pre-operative
      risk assessment and management of these patients. The following provides a review
      of the cardiovascular challenges in LT candidates, as well as evidence-based
      recommendations for their evaluation and management.

PMID- 21737012
TI  - Reduced adipose tissue inflammation represents an intermediate cardiometabolic
      phenotype in obesity.
AB  - OBJECTIVES: The purpose of this study was to determine whether obese individuals
      with reduced adipose tissue inflammation exhibit a more favorable cardiovascular
      risk profile. BACKGROUND: Obesity is associated with a low-grade state of chronic
      inflammation that might be causally related to cardiometabolic disease. METHODS:
      With immunohistochemistry, we categorized obese individuals dichotomously as
      having inflamed fat (n = 78) or noninflamed fat (n = 31) on the basis of the
      presence (+) or absence (-) of macrophage crown-like structures (CLS) in
      subcutaneous abdominal fat biopsy samples. We compared their metabolic, vascular,
      and adipose tissue characteristics with lean subjects (n = 17). RESULTS: Inflamed
      CLS+ obese individuals displayed higher plasma insulin, homeostasis model
      assessment, triglycerides, glucose, blood pressure, high-sensitivity C-reactive
      protein, low-density lipoprotein cholesterol, lower high-density lipoprotein
      cholesterol, and brachial artery flow-mediated dilation compared with lean
      subjects (p < 0.05). Adipose messenger ribonucleic acid expression of
      inflammatory genes including CD68, leptin, matrix metalloproteinase-9, CD163, and
      CD8A were significantly greater and vascular endothelial growth factor was lower
      in the CLS+ group (p < 0.05). In contrast, obese subjects with noninflamed fat
      exhibited a mixed clinical phenotype with lower insulin resistance, reduced
      proatherogenic gene expression, and preserved vascular function as in lean
      subjects. In multiple linear regression adjusting for age and sex, CLS status
      (beta = -0.28, p = 0.008) and waist circumference (beta = -0.25, p = 0.03) were
      independent predictors of flow-mediated dilation. CONCLUSIONS: These findings
      lend support to the novel concept that factors in addition to absolute weight
      burden, such as qualitative features of adipose tissue, might be important
      determinants of cardiovascular disease. Therapeutic modulation of the adipose
      phenotype might represent a target for treatment in obesity.

PMID- 21737013
TI  - Vascular generation of tumor necrosis factor-alpha reduces nitric oxide
      availability in small arteries from visceral fat of obese patients.
AB  - OBJECTIVES: The aim of this study was to assess whether small arteries from
      visceral fat of obese patients show a reduced nitric oxide (NO)-dependent
      relaxation, as compared with lean control subjects, focusing on the role of the
      pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha. BACKGROUND: Visceral
      obesity is characterized by endothelial dysfunction. METHODS: Small arteries from
      14 obese (body mass index 48.4 +/- 11 kg/m(2)) and 14 control subjects (body mass
      index 24.9 +/- 2 kg/m(2)), dissected after a visceral fat biopsy (laparoscopy),
      were evaluated on a pressurized micromyograph. Endothelium-dependent relaxation
      was assessed by acetylcholine. The NO availability, superoxide production, and
      inflammation were assessed by testing acetylcholine under the nitric oxide
      synthase (NOS) inhibitor N(omega)-nitro-L-arginine methylester, tempol
      (superoxide scavenger), and infliximab (monoclonal anti-TNF-alpha antibody),
      respectively. The roles of nicotinamide adenine dinucleotide phosphate oxidase
      and inducible nitric oxide synthase (iNOS) were assessed by their selective
      inhibitors apocynin and S-methylisothiourea (SMT), respectively. Vascular
      superoxide generation (dihydroethidium staining) protein expression of TNF-alpha
      and NOS isoforms (Western Blot) and TNF-alpha localization (immunohistochemistry)
      were assessed. RESULTS: Vessels from obese patients displayed a blunted
      relaxation to acetylcholine and a reduced inhibitory effect of N(omega)-nitro-L
      arginine methylester. These alterations were normalized by tempol or infliximab
      while being partly ameliorated by apocynin and SMT. Vascular superoxide
      generation was increased (p < 0.01) in obese patients. This condition was
      abrogated by both tempol and infliximab and partly (p < 0.05 vs. control
      subjects) reduced by apocynin or SMT. Enhanced TNF-alpha and iNOS expression
      together with increased TNF-alpha localization in the vascular media were
      detected. CONCLUSIONS: Small arteries from visceral fat of obese patients are
      characterized by an increased TNF-alpha production, which reduces NO availability
      by promoting superoxide generation via nicotinamide adenine dinucleotide
      phosphate oxidase and iNOS activation.

PMID- 21737014
TI  - Coronary atherosclerosis is associated with macrophage polarization in epicardial
      adipose tissue.
AB  - OBJECTIVES: The purpose of this report was to assess the link between macrophage
      polarization in epicardial adipose tissue and atherosclerosis in patients with
      coronary artery disease (CAD). BACKGROUND: Macrophage accumulation enhances
      chronic inflammation in adipose tissue, but macrophage phenotypic change in human
      epicardial adipose tissue and its role in atherogenesis are unknown. METHODS:
      Samples were obtained from epicardial and subcutaneous adipose tissue during
      elective cardiac surgery (CAD, n = 38; non-CAD, n = 40). Infiltration of M1/M2
      macrophages was investigated by immunohistochemical staining with antibodies
      against CD11c and CD206, respectively. Expression of pro- and anti-inflammatory
      adipocytokines in adipose tissue was evaluated by real-time quantitative
      polymerase chain reaction. RESULTS: Infiltration of macrophages and expression of
      pro- and anti-inflammatory cytokines were enhanced in epicardial fat of patients
      with CAD compared with that in non-CAD patients (p < 0.05). The ratio of M1/M2
      macrophages was positively correlated with the severity of CAD (r = 0.312, p =
      0.039). Furthermore, the expression of pro-inflammatory cytokines was positively
      correlated, and the expression of anti-inflammatory cytokines was negatively
      correlated with the ratio of M1/M2 macrophages in epicardial adipose tissue of
      CAD patients. By contrast, there was no significant difference in macrophage
      infiltration and cytokine expression in subcutaneous adipose tissue between the
      CAD and non-CAD groups. CONCLUSIONS: The ratio of M1/M2 macrophages in epicardial
      adipose tissue of CAD patients is changed compared with that in non-CAD patients.
      Human coronary atherosclerosis is associated with macrophage polarization in
      epicardial adipose tissue.

PMID- 21737015
TI  - An inflammatory tale from 3 fatty depots.

PMID- 21737016
TI  - 6-month clinical outcomes following implantation of the bioresorbable everolimus
      eluting vascular scaffold in vessels smaller or larger than 2.5 mm.
AB  - OBJECTIVES: We investigated the 6-month clinical outcomes after implantation of
      second-generation 3.0-mm bioresorbable everolimus-eluting vascular scaffolds
      (BVS) in small coronary vessels (<2.5 mm). BACKGROUND: BVS are a novel approach
      to treating coronary lesions and are untested in small vessels. METHODS: The
      ABSORB Cohort B Trial is a multicenter, single-arm, prospective, open-label trial
      assessing the performance of the second-generation BVS, in which 101 patients
      were enrolled. The pre-procedural reference vessel diameter (RVD) was assessed by
      quantitative coronary angiography during post hoc analysis. The vessel size was
      overestimated, by visual assessment, in 41 patients before implantation of 3.0-mm
      BVS in vessels with a pre-procedural RVD <2.5 mm. The study population was
      divided into 2 groups, group I (n = 41) with RVD <2.5 mm and group II (n = 60)
      with RVD >=2.5 mm. The composite endpoint of ischemia-driven major adverse
      cardiac events, defined as ischemia-driven target lesion revascularization,
      myocardial infarction, or cardiac death, was assessed. Of the 45 patients
      scheduled for 6-month coronary angiography, 42 patients had the procedure
      performed, with intravascular ultrasound undertaken in 40 of these patients.
      RESULTS: At 6 months, no significant differences in ischemia-driven major adverse
      cardiac events (3 of 41 [7.3%] cases vs. 2 of 60 [3.3%] cases; p = 0.3933) were
      observed in the small- and large-vessel groups, respectively. No cardiac deaths
      or episodes of in-scaffold thromboses were seen. Angiographic and intravascular
      ultrasound follow-up demonstrated no differences in late lumen loss (0.16 +/-
      0.18 mm vs. 0.21 +/- 0.17 mm; p = 0.3525) or percentage lumen area stenosis (17.6
      +/- 6.0% vs. 19.8 +/- 8.5%; p = 0.3643). CONCLUSIONS: The second-generation 3.0
      mm BVS appears to be safe in small vessels, with similar clinical and
      angiographic outcomes compared with those of large vessels.

PMID- 21737018
TI  - Heart failure with a preserved ejection fraction: what is in a name?

PMID- 21737017
TI  - Determinants of exercise intolerance in elderly heart failure patients with
      preserved ejection fraction.
AB  - OBJECTIVES: The purpose of this study was to determine the mechanisms responsible
      for reduced aerobic capacity (peak Vo(2)) in patients with heart failure with
      preserved ejection fraction (HFPEF). BACKGROUND: HFPEF is the predominant form of
      heart failure in older persons. Exercise intolerance is the primary symptom among
      patients with HFPEF and a major determinant of reduced quality of life. In
      contrast to patients with heart failure and reduced ejection fraction, the
      mechanism of exercise intolerance in HFPEF is less well understood. METHODS: Left
      ventricular volumes (2-dimensional echocardiography), cardiac output, Vo(2), and
      calculated arterial-venous oxygen content difference (A-Vo(2) Diff) were measured
      at rest and during incremental, exhaustive upright cycle exercise in 48 HFPEF
      patients (age 69 +/- 6 years) and 25 healthy age-matched controls. RESULTS: In
      HFPEF patients compared with healthy controls, Vo(2) was reduced at peak exercise
      (14.3 +/- 0.5 ml.kg.min(-1) vs. 20.4 +/- 0.6 ml.kg.min(-1); p < 0.0001) and was
      associated with a reduced peak cardiac output (6.3 +/- 0.2 l.min(-1) vs. 7.6 +/-
      0.2 l.min(-1); p < 0.0001) and A-Vo(2) Diff (17 +/- 0.4 ml.dl(-1) vs. 19 +/- 0.4
      ml.dl(-1), p < 0.0007). The strongest independent predictor of peak Vo(2) was the
      change in A-Vo(2) Diff from rest to peak exercise (A-Vo(2) Diff reserve) for both
      HFPEF patients (partial correlate, 0.58; standardized beta coefficient, 0.66; p =
      0.0002) and healthy controls (partial correlate, 0.61; standardized beta
      coefficient, 0.41; p = 0.005). CONCLUSIONS: Both reduced cardiac output and A
      Vo(2) Diff contribute significantly to the severe exercise intolerance in elderly
      HFPEF patients. The finding that A-Vo(2) Diff reserve is an independent predictor
      of peak Vo(2) suggests that peripheral, noncardiac factors are important
      contributors to exercise intolerance in these patients.

PMID- 21737019
TI  - Impact of implanted recalled sprint Fidelis lead on patient mortality.
AB  - OBJECTIVES: This study sought to compare all-cause mortality in patients with
      Fidelis leads (Medtronic, Minneapolis, Minnesota) to those with a nonadvisory
      lead. BACKGROUND: Although Fidelis leads are prone to fracture, and rare deaths
      due to lead failure have been reported, it is unclear whether the presence of a
      Fidelis lead is associated with increased mortality. This study compares all
      cause mortality in a large cohort of patients with Fidelis and Quattro
      implantable cardioverter-defibrillator (ICD) leads. METHODS: All patients with
      Fidelis (Medtronic models 6931, 6948, and 6949) and Quattro (Medtronic model
      6947) leads followed at 3 tertiary care centers were identified from the medical
      records (implant dates: November 19, 2001, to December 23, 2008). Clinical and
      device-specific data were collected into a common database. Deaths were
      identified from medical records and the Social Security Death Index. Survival was
      estimated using the Kaplan-Meier method. RESULTS: A total of 2,671 patients
      (1,030 Fidelis and 1,641 Quattro) were identified. There were 398 deaths: 147 in
      the Fidelis group (mean follow-up: 34.4 months) and 251 in the Quattro group
      (mean follow-up: 39.9 months). No deaths were associated with 85 Fidelis and 23
      Quattro failures. At 4 years, survival was diminished in patients with Fidelis
      compared with Quattro leads (80.7% vs. 83.9%, p = 0.025). After adjustment for
      factors associated with mortality, survival was similar between groups. One
      hundred percent pacing was not associated with mortality. Elective removal of
      nonfailed leads was performed in 5.1% of Fidelis and 0.9% of Quattro patients.
      CONCLUSIONS: In a conservatively managed cohort, in whom observation was
      predominantly utilized, adjusted survival is similar between patients with
      Fidelis and Quattro ICD leads.

PMID- 21737020
TI  - Mortality risk of Fidelis management.

PMID- 21737021
TI  - Prevalence of J-point elevation in sudden arrhythmic death syndrome families.
AB  - OBJECTIVES: The purpose of this study was to assess the prevalence of J-point
      elevation among the relatives of sudden arrhythmic death syndrome (SADS)
      probands. BACKGROUND: J-point elevation is now known to be associated with
      idiopathic ventricular fibrillation. We hypothesized that this early
      repolarization phenomenon is an inherited trait responsible for a proportion of
      otherwise unexplained SADS cases. METHODS: Families of SADS probands were
      evaluated in an inherited arrhythmia clinic. Twelve-lead electrocardiograms were
      analyzed for J-point elevation defined as >0.1 mV from baseline present in 2 or
      more of the inferior (II, III, and aVF) or lateral (1, aVL, V(4) to V(6)) leads.
      Electrocardiographic data were compared with those of 359 controls of a similar
      age, sex, and ethnic distribution. RESULTS: A total of 363 first-degree relatives
      from 144 families were evaluated. J-point elevation in the inferolateral leads
      was present in 23% of relatives and 11% of control subjects (odds ratio: 2.54,
      95% confidence interval: 1.66 to 3.90; p < 0.001). CONCLUSIONS: J-point elevation
      is more prevalent in the relatives of SADS probands than in controls. This
      indicates that early repolarization is an important potentially inheritable pro
      arrhythmic trait or marker of pro-arrhythmia in SADS.

PMID- 21737022
TI  - Association of serum phosphate levels with aortic valve sclerosis and annular
      calcification: the cardiovascular health study.
AB  - OBJECTIVES: This study was conducted to evaluate mineral metabolism markers as
      potential risk factors for calcific aortic valve disease. BACKGROUND: Mineral
      metabolism disturbances are common among older people and may contribute to
      cardiac valvular calcification. Associations of serum mineral metabolism markers
      with cardiac valvular calcification have not been evaluated in a well
      characterized general population of older adults. METHODS: We measured serum
      levels of phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D in
      1,938 Cardiovascular Health Study participants who were free of clinical
      cardiovascular disease and who underwent echocardiographic measurements of aortic
      valve sclerosis (AVS), mitral annular calcification (MAC), and aortic annular
      calcification (AAC). We used logistic regression models to estimate associations
      of mineral metabolism markers with AVS, MAC, and AAC after adjustment for
      relevant confounding variables, including kidney function. RESULTS: The
      respective prevalences of AVS, MAC, and AAC were 54%, 39%, and 44%. Each 0.5
      mg/dl higher serum phosphate concentration was associated with greater adjusted
      odds of AVS (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.04 to 1.31, p
      = 0.01), MAC (OR: 1.12, 95% CI: 1.00 to 1.26, p = 0.05), and AAC (OR: 1.12, 95%
      CI: 0.99 to 1.25, p = 0.05). In contrast, serum calcium, parathyroid hormone, and
      25-hydroxyvitamin D concentrations were not associated with aortic or mitral
      calcification. CONCLUSIONS: Higher serum phosphate levels within the normal range
      were associated with valvular and annular calcification in a community-based
      cohort of older adults. Phosphate may be a novel risk factor for calcific aortic
      valve disease and warrants further study.

PMID- 21737023
TI  - Serum phosphate concentrations: a novel pre-clinical biomarker for cardiovascular
      calcification.

PMID- 21737024
TI  - Iron deficiency and raised hepcidin in idiopathic pulmonary arterial
      hypertension: clinical prevalence, outcomes, and mechanistic insights.
AB  - OBJECTIVES: This study sought to understand the prevalence and clinical relevance
      of iron deficiency in patients with idiopathic pulmonary arterial hypertension
      (IPAH). BACKGROUND: Iron availability influences the pulmonary vascular response
      to hypoxia in humans and may be significant in the pathogenesis of IPAH. METHODS:
      Iron deficiency, defined by raised levels of soluble transferrin receptor (sTfR),
      was investigated in 98 patients with IPAH. Hepcidin and erythropoietin (EPO)
      levels were also measured. The effect of bone morphogenetic protein (BMP)
      receptor knockdown on BMP-6-stimulated hepcidin production was assessed in human
      hepatoma HepG2 cells. Relationships between sTfR and exercise capacity,
      functional class, and all-cause mortality were analyzed. RESULTS: Circulating
      sTfR levels were raised in 63% of IPAH patients, indicating significant iron
      deficiency. Consistent with this, iron, ferritin, and transferrin saturation
      levels were reduced and red cell distribution width increased, without overt
      anemia. Hepcidin correlated inversely with sTfR and positively with increasing
      ferritin. Hepcidin was inappropriately raised in IPAH independent of the
      inflammatory marker interleukin-6. EPO levels were also raised and correlated
      inversely with hepcidin. BMP receptor-type 2 (BMPR2) knockdown in HepG2 cells
      increased BMP-6-stimulated hepcidin expression. sTfR increased with World Health
      Organization functional class (p < 0.05), correlated negatively with exercise
      capacity (p = 0.027), and values >28.1 nmol/l independently predicted survival (p
      = 0.011). CONCLUSIONS: Iron deficiency is common in IPAH patients and associated
      with disease severity and poor clinical outcome. Inappropriately raised hepcidin
      levels, which impair iron absorption from the gut, may be a factor.

PMID- 21737025
TI  - A new diagnosis of severe aortic coarctation presenting in adult life.

PMID- 21737026
TI  - Histopathological features of delayed enhancement cardiovascular magnetic
      resonance in isolated left ventricular noncompaction.

PMID- 21737027
TI  - Diagnostic criteria for percutaneous coronary intervention-related myocardial
      infarction: time for revision?

PMID- 21737029
TI  - "Universal definition" methodology and conclusions are a concern.

PMID- 21737031
TI  - Bridging with the sacred: reflections of an MD chaplain.

PMID- 21737032
TI  - Pc-facs.
AB  - PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care), an
      electronic publication of the American Academy of Hospice and Palliative
      Medicine, provides palliative care clinicians with concise summaries of the most
      important findings from more than 50 medical and scientific journals. Each month,
      structured summaries and insightful commentaries on 6-10 articles help palliative
      care clinicians stay on top of the research that is critical to contemporary
      practice. PC-FACS is free to AAHPM members and members can earn up to 3 CME
      credits quarterly. Following are excerpts from recent issues, and comments from
      readers are welcomed at resources@aahpm.org.

PMID- 21737033
TI  - The burden of allergic rhinitis beyond allergies.

PMID- 21737035
TI  - Current understanding of the pathophysiology of allergic rhinitis.
AB  - The immune response to an allergen depends on an initial sensitization process,
      with future exposures triggering a 2-part allergic response including an early
      and late phase. The process by which an allergen is recognized has become
      clearer. Similarly, the roles of the preformed mediators responsible for many of
      the signs and symptoms of the early-phase response have been elucidated. Recent
      work also has shed some light on the cells and mediators involved in the late
      phase reactions. This article discusses some of this recent work and reviews the
      basics behind of all of the stages of the allergic response.

PMID- 21737036
TI  - Nonallergic rhinopathy (formerly known as vasomotor rhinitis).
AB  - This review focuses on the poorly understood condition of nonallergic rhinopathy
      (NAR) at a clinical level, with an eye on current optimal treatment. NAR is the
      new designation for the conditions formerly referred to as vasomotor rhinitis or
      nonallergic idiopathic rhinitis. The clinical characteristics and differential
      diagnosis are provided in detail in this review, and the disease should now be
      characterized sufficiently for clinical studies.

PMID- 21737037
TI  - Other causes of rhinitis: mixed rhinitis, rhinitis medicamentosa, hormonal
      rhinitis, rhinitis of the elderly, and gustatory rhinitis.
AB  - It is important to consider a comprehensive differential of possible rhinitis
      types when considering the diagnosis of chronic rhinitis, including at least 9
      subtypes of nonallergic rhinitis: drug-induced rhinitis, gustatory rhinitis,
      hormonal-induced rhinitis, infectious rhinitis, nonallergic rhinitis with
      eosinophilia syndrome, occupational rhinitis, senile rhinitis, atrophic rhinitis,
      and nonallergic rhinopathy. This article focuses on some of the most common types
      of chronic rhinitis, including mixed rhinitis (allergic and nonallergic overlap),
      rhinitis medicamentosa, hormonal rhinitis, rhinitis of the elderly, and gustatory
      rhinitis.

PMID- 21737038
TI  - What are the primary clinical symptoms of rhinitis and what causes them?
AB  - The nose has a limited repertoire of responses regardless of the triggers. These
      responses primarily serve as a protective mechanism for the lower respiratory
      tract. Although the nasal reactions to pollens, particles, and pollution may have
      a beneficial effect for the lower airway, they create symptoms in some
      individuals that lead to significant morbidity. The symptoms of allergic rhinitis
      extend far beyond the nose, and the morbidity associated with rhinitis is
      significant. The nasal symptoms of rhinitis and their causes are the focus of
      this review.

PMID- 21737039
TI  - The relationship of rhinitis and asthma, sinusitis, food allergy, and eczema.
AB  - Epidemiologic, genetic, immunologic, and clinical studies show a close
      relationship between allergic rhinitis and asthma, food allergy, and atopic
      dermatitis. Rhinitis and sinusitis often coexist and are commonly referred to
      with the term rhinosinusitis. These conditions are also linked in the so-called
      atopic march, which is the sequential appearance of atopic manifestations
      starting with atopic dermatitis and later followed by food allergy, allergic
      rhinitis, and asthma. Allergic rhinitis and asthma are now increasingly being
      approached diagnostically and therapeutically as the one-airway concept.

PMID- 21737040
TI  - Does allergen avoidance work?
AB  - Allergic rhinitis affects a large portion of the population. Patients are
      frequently sensitized to indoor allergens. The most important contributors are
      house dust mites, pets, and fungi. In very controlled environments where allergen
      exposure is significantly reduced, individuals have been shown to have clinical
      improvement in allergic rhinitis and/or asthma symptoms. Achieving sufficient
      exposure reduction in the home has proven difficult. Nonetheless, evidence exists
      that demonstrates exposure avoidance can be useful as an adjunct to other
      therapies, such as pharmacotherapy and immunotherapy, for the treatment of
      allergic rhinitis.

PMID- 21737041
TI  - Antihistamine therapy in allergic rhinitis.
AB  - Antihistamines have long been a mainstay in the therapy for allergic rhinitis.
      Many different oral antihistamines are available for use, and they are classified
      as first generation or second generation based on their pharmacologic properties
      and side-effect profiles. The recent introduction of intranasal antihistamines
      has further expanded the role of antihistamines in the treatment of allergic
      rhinitis. Certain patient populations, such as children and pregnant or lactating
      women, require special consideration regarding antihistamine choice and dosing as
      part of rhinitis therapy.

PMID- 21737042
TI  - The role of nasal corticosteroids in the treatment of rhinitis.
AB  - Intranasal corticosteroids (INSs) are the first choice for rhinitis
      pharmacotherapy. This preference is because of their broad range of actions that
      result in reductions of proinflammatory mediators, cytokines, and cells. Over the
      past 30 years, INSs have been modified to improve their pharmacodynamic,
      pharmacokinetic, and delivery system properties, with attention to improving
      characteristics such as receptor binding affinity, lipophilicity, low systemic
      bioavailability, and patient preference. Clinically, they have been shown to be
      the most effective class of nasal medications for treating allergic rhinitis and
      nonallergic rhinopathy, with no clear evidence that any specific INS is superior
      to others.

PMID- 21737043
TI  - Specific allergy immunotherapy for allergic rhinitis: subcutaneous and
      sublingual.
AB  - Numerous controlled clinical trials have demonstrated the efficacy of specific
      allergen immunotherapy (SIT) in reducing the clinical symptoms and costs
      associated with allergic rhinitis. Compared with pharmacotherapy, SIT may provide
      persistent clinical benefits after treatment discontinuation. Subcutaneous and
      sublingual immunotherapy are the two most widely prescribed SIT routes worldwide.
      This review compares the efficacy, safety, preventive effect, immunologic
      mechanisms, and adherence rates associated with these two forms of SIT.

PMID- 21737044
TI  - The role of decongestants, cromolyn, guafenesin, saline washes, capsaicin,
      leukotriene antagonists, and other treatments on rhinitis.
AB  - Clinical symptoms of allergic and nonallergic rhinitis are similar despite the
      significant difference in underlying mechanisms. Over-the-counter (OTC)
      treatments can be used as effective and affordable therapeutic modalities when
      recommended by a physician. Adjunct treatments, such as herbal medicine,
      acupuncture and homeopathy, have become increasingly popular. Most of the
      treatments reviewed in this article are available OTC and are a likely choice for
      patients suffering from acute or chronic rhinitis. This article provides an
      overview of treatment suggestions, benefits, and side effects for available OTC,
      prescription drug, and alternative choices in addition to the therapies described
      in other articles.

PMID- 21737045
TI  - Management of rhinitis: guidelines, evidence basis, and systematic clinical
      approach for what we do.
AB  - Whereas very mild rhinitis may be simply and successfully self-managed by
      patients using medications available over the counter, most patients with
      rhinitis who present to medical offices have more severe rhinitis that may need a
      more comprehensive diagnostic and therapeutic approach. Optimal care may require
      special diagnostic studies and combination therapies that are arrived at only
      after trying multiple different medication and therapeutic options. This article
      presents a systematic approach to office care of rhinitis from the perspective of
      an allergist-immunologist. More emphasis is given to discussion of dilemmas that
      face the specialist or more involved considerations that have been highlighted in
      recently published guidelines.

PMID- 21737046
TI  - Socioeconomic indicators and the risk of acute coronary heart disease events:
      comparison of population-based data from the United States and Finland.
AB  - PURPOSE: We wished to determine whether a gradient of association of low
      socioeconomic status with incidence of coronary heart disease was present in two
      population-based cohorts, one from United States and the other from Finland.
      METHODS: Using data from the Atherosclerosis Risk in Communities (ARIC) cohort
      and the Finnish FINRISK cohort, we estimated, with Cox proportional hazard
      regression models, incidence of sudden cardiac death (SCD), non-sudden cardiac
      death (NSCD), and non-fatal myocardial infarction (NFMI) for strata of income and
      education (follow-up: 1987-2001). In both cohorts, incidence rates of the three
      outcomes increased across all socioeconomic status exposure categories. RESULTS:
      Low education was associated with increased hazard of NFMI in both cohorts and
      with increased risk of SCD among ARIC women. Low income was significantly
      associated with increased hazard of all three outcomes among ARIC women and with
      increased hazard of cardiac death among ARIC men. In FINRISK, low income was
      significantly associated with increased risk of SCD only. Risk of SCD in the low
      income categories was similar for both cohorts. Smoking, alcohol consumption, and
      race (ARIC only) did not appreciably alter effect estimates in either cohort.
      CONCLUSIONS: Indices of low SES show similar associations with increased risk of
      cardiac events in Finland and in United States.

PMID- 21737047
TI  - Life course models of socioeconomic position and cardiovascular risk factors:
      1946 birth cohort.
AB  - PURPOSE: To identify the life course model that best describes the association
      between life course socioeconomic position (SEP) and cardiovascular (CVD) risk
      factors (ie, body mass index [BMI], systolic and diastolic blood pressure, total
      cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides,
      and glycated hemoglobin) and explore BMI across the life course as mediators of
      the relationship. METHODS: The Medical Research Council National Survey of Health
      and Development was used to compare partial F-tests of simpler nested life course
      SEP models corresponding to critical period, accumulation, and social mobility
      models with a saturated model. Then, the chosen life course model for each CVD
      risk factor was adjusted for BMI at age 53 and lifetime BMI (ages 4, 26, 43, and
      53 years). RESULTS: Among women, SEP was generally associated with CVD risk
      factors in a cumulative manner, whereas childhood critical period was the
      prominent model for men. When the best-fitting SEP models were used, we found
      that adjustment for BMI at age 53 reduced associations for all outcomes in both
      genders. Further adjustment for lifetime BMI (4, 26, 43, and 53 years) did not
      substantially alter most associations (except for triglycerides). CONCLUSIONS:
      SEP at different points across life influences CVD risk factors differently in
      men and women.

PMID- 21737048
TI  - Spectrum of cardiovascular diseases inAsian-American racial/ethnic subgroups.
AB  - PURPOSE: To compare the prevalence of coronary heart disease (CHD), stroke, and
      peripheral vascular disease (PVD) across Asian-American subgroups (Asian Indian,
      Chinese, Filipino, Japanese, Korean, and Vietnamese) and non-Hispanic white (NHW)
      subjects in a mixed-payer, outpatient health care organization in California.
      METHODS: Electronic health records from 2007 to 2010 were examined for 94,423
      Asian and NHW patients. Age-adjusted prevalence rates of CHD, stroke, and PVD,
      defined by physician International Classification of Diseases, Version 9, codes,
      were directly standardized to the NHW population. Age-adjusted odds ratios were
      calculated by the use of logistic regression for each Asian subgroup, by sex,
      compared with NHWs. RESULTS: The range of age-adjusted prevalence rates were: CHD
      (1.7%-5.2%), stroke (0.3%-1.8%), and PVD (0.9%-3.4%). The adjusted odds ratios of
      CHD were significantly higher for Filipino women (1.66; 95% confidence interval;
      1.13-2.43) and men (1.47, 1.05-2.06) and Asian Indian men (1.77, 1.43-2.21), and
      significantly lower for Chinese women (0.72, 0.55-0.94) and men (0.78, 0.65
      0.93), compared with NHWs. The odds of stroke were significantly greater for
      Filipino women (2.02, 1.22-3.34). The odds of PVD were generally lower for all
      Asian subgroups. CONCLUSION: There is considerable heterogeneity across Asian
      subgroups for prevalent CHD, stroke, and PVD. Future research should disaggregate
      Asian subgroups and cardiovascular outcomes to inform targeted prevention and
      treatment efforts.

PMID- 21737049
TI  - Racial and ethnic disparities in hospitalizations and deaths associated with 2009
      pandemic Influenza A (H1N1) virus infections in the United States.
AB  - PURPOSE: Concerns have been raised regarding possible racial-ethnic disparities
      in 2009 pandemic influenza A (H1N1) (pH1N1) illness severity and health
      consequences for U.S. minority populations. METHODS: Using data from the Centers
      for Disease Control and Prevention's Behavioral Risk Factor Surveillance System,
      Emerging Infections Program Influenza-Associated Hospitalization Surveillance,
      and Influenza-Associated Pediatric Mortality Surveillance, we calculated race
      ethnicity-specific, age-adjusted rates of self-reported influenza-like illness
      (ILI) and pH1N1-associated hospitalizations. We used chi(2) tests to evaluate
      racial-ethnic disparities in ILI-associated health care-seeking behavior and
      pH1N1 hospitalization. To evaluate pediatric deaths, we compared racial-ethnic
      proportions of deaths against U.S. population distributions. RESULTS: Prevalence
      of self-reported ILI was lower among Hispanics (6.5%), higher among American
      Indians/Alaska Natives (16.2%), and similar among non-Hispanic blacks (7.7%)
      compared with non-Hispanic whites (8.5%). No racial-ethnic differences were
      identified in ILI-associated health care-seeking behavior. Age-adjusted pH1N1
      associated Emerging Infections Program hospitalization rates were higher among
      all minority populations (range: 8.1-10.9/100,000 population) compared with non
      Hispanic whites (3.0/100,000). The proportion of pH1N1-associated pediatric
      deaths was higher than expected among Hispanics (31%) and lower than expected
      among non-Hispanic whites (45%) given the proportions of the U.S. population they
      comprise (22% and 58%, respectively). CONCLUSIONS: Racial-ethnic disparities in
      pH1N1-associated hospitalizations and pediatric deaths were identified.
      Vaccination remains the primary intervention for preventing influenza.

PMID- 21737050
TI  - Black preterm birth risk in nonblack neighborhoods: effects of Hispanic, Asian,
      and non-Hispanic white ethnic densities.
AB  - PURPOSE: Studies of ethnic density and health in the United States have
      documented poorer health outcomes among black individuals living in black
      compared with nonblack neighborhoods, but few studies have considered the
      identities of the populations in nonblack neighborhoods. METHODS: New York City
      birth records from 1995 through 2003 and a spatial measure of ethnic density were
      used to examine preterm birth risks among non-Hispanic black women associated
      with non-Hispanic white, Hispanic, Asian, and non-Hispanic black neighborhood
      densities. Logistic regression models were used to estimate the effect on black
      preterm birth risks of replacing white neighbors with Hispanic, Asian, and black
      neighbors. Risk differences were computed for changes from the 10th to the 90th
      percentiles of ethnic density. RESULTS: Increasing Hispanic density was
      associated with reduced preterm birth risks among non-Hispanic black women,
      especially if the black women were foreign-born (RD = -19.1 per 1,000 births; 95%
      confidence interval. -28.6 to -9.5). Estimates for increasing Asian density were
      null. Increasing black density was associated with increasing black preterm birth
      risk, with a threshold at greater levels of black density. CONCLUSIONS: The low
      risks of preterm birth among foreign-born non-Hispanic black women in majority
      Hispanic neighborhoods may be related to protective psychosocial or lifestyle and
      warrant further investigation.

PMID- 21737051
TI  - Thrombosed phlebectasia of the external jugular vein with neck pain.
AB  - Jugular phlebectasia is a dilation of the vein. It is observed clinically as a
      soft, bulky tumour in the neck, with no pain. Rarely seen in adults, there are
      only a few cases described in the literature. We report a 72-year-old patient who
      reported a painful cervical mass. Extension studies led to the diagnosis of
      phlebectasia of the external jugular vein with partial thrombosis. The elective
      treatment is conservative, but considering the possibility of rupture or
      thromboembolic complication, we performed surgical exeresis of the lesion.

PMID- 21737052
TI  - Exploring cross-task compatibility in perceiving and producing facial expressions
      using electromyography.
AB  - Using a dual-task methodology we examined the interaction of perceiving and
      producing facial expressions. In one task, participants were asked to produce a
      smile or a frown (Task 2) in response to a tone stimulus. This auditory-facial
      task was embedded in a dual-task context, where the other task (Task 1) required
      a manual response to visual face stimuli (visual-manual task). These face stimuli
      showed facial expressions that were either compatible or incompatible to the to
      be-produced facial expression. Both reaction times and error rates (measured by
      facial electromyography) revealed a robust stimulus-response compatibility effect
      across tasks, suggesting that perceived social actions automatically activate
      corresponding actions even if perceived and produced actions belong to different
      tasks. The dual-task nature of this compatibility effect further testifies that
      encoding of facial expressions is highly automatic.

PMID- 21737053
TI  - [Phenotypic and histologic characteristics of cutaneous melanoma in patients with
      melanocortin-1 receptor polymorphisms].
AB  - BACKGROUND: The melanocortin-1 receptor (MC1R) is an important risk factor for
      melanoma due to its role in the production of melanin in response to sun
      exposure. OBJECTIVES: To analyze the phenotypic and histologic characteristics of
      cutaneous melanoma in patients carrying mutations in MC1R and assess the
      influence of sun exposure on the occurrence of melanoma. MATERIAL AND METHODS: A
      total of 224 patients with a diagnosis of melanoma seen in the Department of
      Dermatology at Hospital General Universitario Gregorio Maranon in Madrid, Spain
      between September 2004 and December 2009 were included in the study. The genomic
      sequence of MC1R was analyzed by polymerase chain reaction. RESULTS: At least one
      of the following MC1R variants was present in 58% of the patients: V60L, V92M,
      I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of
      sunburn (P=.018) and melanomas located on areas with intermittent sun exposure
      (P=.019), and the majority had a diagnosis of superficial spreading melanoma.
      These associations were especially significant in patients with the R160W and
      D294H variants. Carriers of R160W also had melanomas associated with melanocytic
      nevi (P=.028). CONCLUSIONS: The results of our study suggest that there may be a
      relationship between the expression of certain MC1R variants and sun exposure,
      history of sunburn, and skin type. They also indicate a higher frequency of
      superficial spreading melanomas and melanomas associated with melanocytic nevi in
      patients carrying certain mutations in MC1R.

PMID- 21737054
TI  - [Skin signs in child abuse].
AB  - Child abuse is far more prevalent today than is generally recognized. Up to 90%
      of victims suffer physical abuse that can be observed in signs on the skin.
      Dermatologists are particularly qualified to identify these signs and distinguish
      them from other conditions that can mimic abuse. This review covers the signs of
      child abuse that can be observed on the skin. We discuss clues that can help
      differentiate between lesions caused by abuse and those that are accidental, and
      we describe the skin conditions that mimic physical abuse.

PMID- 21737055
TI  - [Basic concepts in skin biopsy. Part II].
AB  - In this article, we review some of the artifacts commonly observed in biopsies
      and the methods used to prevent their appearance. We describe the basic
      techniques for taking biopsies of melanocytic lesions, bullous diseases, and from
      special areas such as the scalp and nail region. We also provide a brief summary
      of the role of skin biopsy in the diagnosis of neurological diseases and prenatal
      diagnosis. The aim of this guide is to improve the diagnostic yield of biopsies
      and to highlight the importance of a correct clinical-histological correlation;
      we therefore provide clues to the interpretation of the dermatopathology report.

PMID- 21737056
TI  - [Pellagra: a clinical, histopathological, and epidemiological study of 7 cases].
AB  - BACKGROUND AND OBJECTIVES: In the developed world, pellagra is a rare condition
      that is restricted to a small number of at-risk groups. It mainly affects
      alcoholic patients and those with dietary deficiencies, with intestinal
      malabsorption, or in treatment with certain drugs. The aim of this study was to
      analyze the clinical, histopathological, and epidemiological characteristics of
      patients diagnosed with pellagra in our hospital and to compare the results with
      the findings traditionally described for this disease. PATIENTS AND METHODS: We
      undertook a retrospective study of patients with clinical or pathological
      evidence of pellagra who were seen in our hospital between 1998 and 2009.
      RESULTS: Seven patients met the inclusion criteria. All were men and the most
      common predisposing factors were alcoholism and dietary deficiency. All exhibited
      photosensitivity mainly affecting the forearms and the upper surface of the feet,
      where the lesions were more severe. The most consistent histopathological
      findings were the presence of dilated blood vessels with extravasation and little
      or no inflammatory infiltrate. Various changes were observed in the epidermis,
      including those suggestive of mild pellagra, such as epidermal pallor and some
      degree of ballooning of the keratinocytes. Other abnormalities such as epidermal
      necrosis and hyperkeratosis were also observed. In most patients, pellagra was
      not initially suspected. Additional noncutaneous findings were observed in almost
      all cases. CONCLUSIONS: Pellagra should be ruled out in patients with lesions on
      sun-exposed areas. Predisposing factors for pellagra should be assessed along
      with the social situation of patients and the presence of digestive or
      neurological abnormalities.

PMID- 21737057
TI  - Recent admixture in an Indian population of African ancestry.
AB  - Identification and study of genetic variation in recently admixed populations not
      only provides insight into historical population events but also is a powerful
      approach for mapping disease loci. We studied a population (OG-W-IP) that is of
      African-Indian origin and has resided in the western part of India for 500 years;
      members of this population are believed to be descendants of the Bantu-speaking
      population of Africa. We have carried out this study by using a set of 18,534
      autosomal markers common between Indian, CEPH-HGDP, and HapMap populations.
      Principal-components analysis clearly revealed that the African-Indian population
      derives its ancestry from Bantu-speaking west-African as well as Indo-European
      speaking north and northwest Indian population(s). STRUCTURE and ADMIXTURE
      analyses show that, overall, the OG-W-IPs derive 58.7% of their genomic ancestry
      from their African past and have very little inter-individual ancestry variation
      (8.4%). The extent of linkage disequilibrium also reveals that the admixture
      event has been recent. Functional annotation of genes encompassing the ancestry
      informative markers that are closer in allele frequency to the Indian ancestral
      population revealed significant enrichment of biological processes, such as ion
      channel activity, and cadherins. We briefly examine the implications of
      determining the genetic diversity of this population, which could provide
      opportunities for studies involving admixture mapping.

PMID- 21737058
TI  - Exome sequencing identifies CCDC8 mutations in 3-M syndrome, suggesting that
      CCDC8 contributes in a pathway with CUL7 and OBSL1 to control human growth.
AB  - 3-M syndrome, a primordial growth disorder, is associated with mutations in CUL7
      and OBSL1. Exome sequencing now identifies mutations in CCDC8 as a cause of 3-M
      syndrome. CCDC8 is a widely expressed gene that is transcriptionally associated
      to CUL7 and OBSL1, and coimmunoprecipitation indicates a physical interaction
      between CCDC8 and OBSL1 but not CUL7. We propose that CUL7, OBSL1, and CCDC8 are
      members of a pathway controlling mammalian growth.

PMID- 21737059
TI  - Rare-variant association testing for sequencing data with the sequence kernel
      association test.
AB  - Sequencing studies are increasingly being conducted to identify rare variants
      associated with complex traits. The limited power of classical single-marker
      association analysis for rare variants poses a central challenge in such studies.
      We propose the sequence kernel association test (SKAT), a supervised, flexible,
      computationally efficient regression method to test for association between
      genetic variants (common and rare) in a region and a continuous or dichotomous
      trait while easily adjusting for covariates. As a score-based variance-component
      test, SKAT can quickly calculate p values analytically by fitting the null model
      containing only the covariates, and so can easily be applied to genome-wide data.
      Using SKAT to analyze a genome-wide sequencing study of 1000 individuals, by
      segmenting the whole genome into 30 kb regions, requires only 7 hr on a laptop.
      Through analysis of simulated data across a wide range of practical scenarios and
      triglyceride data from the Dallas Heart Study, we show that SKAT can
      substantially outperform several alternative rare-variant association tests. We
      also provide analytic power and sample-size calculations to help design candidate
      gene, whole-exome, and whole-genome sequence association studies.

PMID- 21737060
TI  - Practice patterns and attitudes about treating abnormal uterine bleeding: a
      national survey of obstetricians and gynecologists.
AB  - OBJECTIVE: We sought to examine the practice patterns and attitudes of
      obstetricians and gynecologists surrounding treatment of abnormal uterine
      bleeding (AUB). STUDY DESIGN: We conducted a cross-sectional study of members of
      the American College of Obstetricians and Gynecologists. Surveys, which were
      distributed using a sequential mixed method (both web- and mail-based) approach,
      included questions about practice characteristics, practice patterns, and
      knowledge about treatment options for AUB. RESULTS: Of 802 questionnaires, 417
      were returned (52%). The most commonly selected first-line choice for AUB
      treatment was combined oral contraceptives (97% anovulatory, 98% ovulatory). The
      levonorgestrel intrauterine system was the next most frequently selected option
      (63% anovulatory, 53% ovulatory). Respondents did not score high on questions
      about the effectiveness of treatments for AUB. Only 25% (n = 86) answered at
      least 2 of the 3 questions correctly. CONCLUSION: Continued education is
      necessary to increase the utilization of the most effective treatment options for
      AUB.

PMID- 21737061
TI  - Prediction of outcome in dichorionic twin pregnancies at 6-10 weeks' gestation.
AB  - OBJECTIVE: The objective of the study was to predict the outcome of dichorionic
      (DC) twin pregnancies at 6-10 weeks' gestation from intertwin discordance in
      crown-rump length (CRL), heart rate (HR), and gestational sac diameter (GSD).
      STUDY DESIGN: Intertwin discordance in CRL, HR, and GSD, was compared in 3 groups
      of DC twin pregnancies with 2 live embryos at 6-10 weeks. In one group, there
      were 2 live births (n = 174), in another 1 live birth (n = 24), and in a third
      group there were no live births (n = 33). Regression analysis was used to
      determine the predictors of outcome. RESULTS: Significant contributors to the
      prediction of 1 intrauterine death were discordance in CRL and GSD. The only
      predictor of 2 deaths was discordance in CRL. Detection rates of screening for
      single or double death, at 10% false-positive rate, were 79.2% and 27.3%,
      respectively. CONCLUSION: In DC twins, intertwin discordance in CRL and GSD at 6
      10 weeks can predict outcome.

PMID- 21737062
TI  - The influence of car-seat design on its character experience.
AB  - Producing higher efficiency cars with less and lighter materials but without
      compromising safety, comfort and driving pleasure might give a competitive
      advantage. In this light, at BMW a new light weight car-seat concept was
      developed based on the human body contour. A possibility to increase the comfort
      is using a seat which elicits positive tactile experiences. However, limited
      information is available on seat characteristics and tactile experiences.
      Therefore, this study describes the contour of three different car-seat designs,
      including a light weight seat, and the recorded corresponding emotion and tactile
      experience of 21 persons sitting in the seats. Results show that the new light
      weight car-seat concept rated well on experienced relaxedness, even with the lack
      of a side support. The most important findings are that hard seats with rather
      high side supports are rated sporty and seats that are softer are rated more
      luxurious.

PMID- 21737063
TI  - Anti-erosive potential of amine fluoride, cerium chloride and laser irradiation
      application on dentine.
AB  - METHODS: Ninety-six dentine samples were prepared from human premolars and
      randomly assigned to eight groups (G1-G8). Samples were treated for 30s with the
      following solutions: placebo (G1/G2), amine fluoride (Elmex fluid; G3/G4), cerium
      chloride (G5/G6) and combined fluoride/cerium chloride application (G7/G8).
      Samples of groups G2, G4, G6 and G8 were additionally irradiated with a carbon
      dioxide laser through the solutions for 30s. Acid resistance was assessed in a
      six-time 5-min consecutive lactic acid (pH 3.0) erosion model and calcium release
      was determined by atomic absorption spectroscopy (AAS). Furthermore, six
      additional samples per group were prepared and subjected to EDS-analysis.
      RESULTS: In the non-irradiated groups, specimens of G1 (placebo) showed the
      highest calcium release when compared to the other treatments (G3, G5 and G7).
      The highest acid resistance was observed for G7. In G3, calcium release was lower
      than in G5, but higher than in G7. In general (except for the placebo groups),
      calcium release in the laser-irradiated groups was higher compared with the
      respective non-irradiated groups. EDS showed a replacement of calcium by cerium
      and of phosphor by fluoride. CONCLUSION: The highest anti-erosive potential was
      found after combined cerium chloride and amine fluoride application. Laser
      irradiation had not adjunctive effect.

PMID- 21737064
TI  - Late-postnatal cannabinoid exposure persistently elevates dendritic spine
      densities in area X and HVC song regions of zebra finch telencephalon.
AB  - Centrally acting cannabinoids are well known for their ability to impair
      functions associated with both learning and memory but appreciation of the
      physiological mechanisms underlying these actions, particularly those that
      persist, remains incomplete. Our earlier studies have shown that song stereotypy
      is persistently reduced in male zebra finches that have been developmentally
      exposed to cannabinoids. In the present work, we examined the extent to which
      changes in neuronal morphology (dendritic spine densities and soma size) within
      brain regions associated with zebra finch vocal learning are affected by late
      postnatal cannabinoid agonist exposure. We found that daily treatment with the
      cannabinoid agonist WIN55212-2 (WIN, 1mg/kg IM) is associated with 27% and 31%
      elevations in dendritic spine densities in the song regions Area X and HVC,
      respectively. We also found an overall increase in cell diameter within HVC.
      Changes in dendritic spine densities were only produced following developmental
      exposure; treatments given to adults that had completed vocal learning were not
      effective. These findings have important implications for understanding how
      repeated cannabinoid exposure can produce significant, lasting alteration of
      brain morphology, which may contribute to altered development and behavior.

PMID- 21737065
TI  - The effect of nNOS inhibitors on toxin-induced cell death in dopaminergic cell
      lines depends on the extent of enzyme expression.
AB  - Nitric oxide is linked with neurodegeneration in Parkinson's disease (PD) through
      the involvement of both inducible (iNOS) and neuronal nitric oxide synthase
      (nNOS). While non-selective NOS inhibitors are neuroprotective, the role of nNOS
      has not been determined using selective NOS inhibitors. The present study
      investigated the neuroprotective effect of selective iNOS and nNOS inhibitors on
      MPP(+)- and MG-132-induced cell death in cell lines with differing levels of nNOS
      expression. Inhibition of endogenously expressed nNOS by 7-NI and ARR17477
      enhanced the toxicity of MPP(+) and MG-132 in N1E-115 cells, whereas in
      transfected SH-SY5Y cells overexpressing nNOS, ARR17477 and 7-NI protected
      against MPP(+)- and MG-132-induced cell death. In contrast, inhibition of iNOS by
      1400W was ineffective in preventing MPP(+) and MG-132 toxicity in these cell
      lines. These results suggest a dual role for NOS in dopaminergic cell viability.
      nNOS is protective against toxic insult when produced endogenously. When nNOS is
      overexpressed, it becomes neurotoxic to cells suggesting that inhibition of nNOS
      may be a promising strategy to prevent cell death in PD.

PMID- 21737066
TI  - Astrocytes and pericytes cooperatively maintain a capillary-like structure
      composed of endothelial cells on gel matrix.
AB  - The gliovascular complex (GVC) is a structural and functional unit located at the
      interface between the cerebral blood flow and neural network. Even though its
      physiological roles have been partially clarified, the contribution of the
      astroglia to maintenance of the cerebral vasculature, which is tightly wired with
      the neuronal network, is only incompletely understood. To elucidate the role of
      astrocytes and pericytes in maintaining the integrity of the capillaries, we
      developed a new GVC model in vitro. Human brain microvascular endothelial cells
      (ECs) plated on a gel matrix developed a capillary-like structure (CLS).
      Pericytes and astrocytes migrated together and adhered to the CLS to form a GVC
      like structure with pericytes between the CLS and astrocytes. Astrocytes together
      with pericytes suppressed CLS degradation to a greater extent than astrocytes
      alone. Fumagillin and suramin, angiogenesis inhibitors, suppressed GVC formation.
      The PDGF receptor inhibitor SU6668 suppressed pericyte/astrocyte migration and
      accelerated CLS degradation, whereas the VEGF receptor inhibitor SU1498 did not
      suppress pericyte/astrocyte migration and both types of cells maintained the CLS
      for a long period of time. Immunohistochemistry revealed aquaporin-4 and agrin
      expression at the junction of ECs and astrocytes. These results indicate the
      importance of both astrocytes and pericytes for maintenance of the cerebral
      microvasculature.

PMID- 21737067
TI  - Catalytic conversion of glucose to 5-hydroxymethyl furfural using inexpensive co
      catalysts and solvents.
AB  - Efficient conversion of glucose to 5-hydroxymethyl furfural (5-HMF), a platform
      chemical for fuels and materials, was achieved using CrCl(2) or CrCl(3) as the
      catalysts with inexpensive co-catalysts and solvents including halide salts in
      dimethyl sulfoxide (DMSO) and several ionic liquids. 5-HMF (54.8%) yield was
      achieved with the CrCl(2)/tetraethyl ammonium chloride system at mild reaction
      conditions (120 degrees C and 1h). The 5-HMF formation reaction was found to be
      faster in ionic liquids than in the DMSO system. Effects of water in the reaction
      system, chromium valence and reaction temperature on the conversion of glucose
      into 5-HMF were discussed in this work.

PMID- 21737068
TI  - [Breast segments: a model for the prevention of deformities in conservative
      surgery for breast cancer].
AB  - Conservative breast cancer surgery requires an exact knowledge on the impact that
      local resection may have on the cosmetic result, and for this reason, the
      characteristics of each breast region must be taken into account. The
      segmentation theory helps to predict the consequences of local resection in each
      breast segment and, at the same time, optimise the choice of the best procedure
      for their prevention. Therefore, surgical planning based on segmentation of the
      breast would help us achieve a current objective of breast oncological surgery: a
      surgery adapted to the breast and the tumour. This article describes the
      different breast segments, their resources and limits for remodelling, and the
      best technical options to prevent deformities in each one of them.

PMID- 21737069
TI  - Diagnostic accuracy of ultrasound for rotator cuff tears in adults: a systematic
      review and meta-analysis.
AB  - AIM: To determine the diagnostic accuracy of ultrasound to detect partial and
      complete thickness rotator cuff tears based on all available clinical trials.
      MATERIALS AND METHODS: An electronic search of databases registering published
      and unpublished literature was conducted. All diagnostic accuracy studies that
      directly compared the accuracy of ultrasound (the index test) to either
      arthroscopic or open surgical findings (the reference test) for rotator cuff tear
      were included. The methodological quality of each included study was assessed
      using the QUADAS form. When appropriate, pooled sensitivity and specificity
      analysis was conducted, with an assessment of the summary receiver operating
      characteristic (ROC) curve for each analysis. RESULTS: Sixty-two studies
      assessing 6007 patients and 6066 shoulders were included. Ultrasonography had
      good sensitivity and specificity for the assessment of partial thickness
      (sensitivity 0.84; specificity 0.89), and full-thickness rotator cuff tears
      (sensitivity 0.96; specificity 0.93). However, the literature poorly described
      population characteristics, assessor blinding, and was based on limited sample
      sizes. The literature assessing transducer frequency was particularly small in
      size. CONCLUSION: Ultrasonography is an appropriate radiological technique for
      the assessment of rotator cuff tears with an acceptable sensitivity and
      specificity. The diagnostic test accuracy of ultrasound is superior for the
      detection of full-thickness compared to partial-thickness cuff tears. Further
      study assessing the effect of transducer frequency is warranted.

PMID- 21737070
TI  - Hundreds of partial pipe replacements conducted in Washington, DC before July
      2004.

PMID- 21737071
TI  - Evidence of impaired endometrial receptivity after ovarian stimulation for in
      vitro fertilization: a prospective randomized trial comparing fresh and frozen
      thawed embryo transfers in high responders.
AB  - Clinical pregnancy rates of 80% and 65% were observed in cycles using thawed and
      fresh embryos, respectively, although embryo quality indicators revealed
      morphologically and numerically inferior embryo cohorts after cryopreservation.
      Subsequent logistic regression analysis controlled for differences in embryo
      quality and revealed significantly greater probability of clinical pregnancy with
      thawed embryos when compared with fresh, suggesting a negative effect of ovarian
      stimulation on endometrial receptivity.

PMID- 21737072
TI  - Evidence of impaired endometrial receptivity after ovarian stimulation for in
      vitro fertilization: a prospective randomized trial comparing fresh and frozen
      thawed embryo transfer in normal responders.
AB  - OBJECTIVE: To compare success rates between fresh ETs after ovarian stimulation
      and frozen-thawed ETs (FET) after artificial endometrial preparation, to compare
      endometrial receptivity. DESIGN: Randomized, controlled trial. SETTING: Private
      fertility center. PATIENT(S): There were 53 patients completing fresh blastocyst
      transfer (fresh group) and 50 patients completing FET (cryopreservation group).
      All were first-time IVF patients aged <41 years, with cycle day 3 FSH <10 mIU/mL
      and 8-15 antral follicles. INTERVENTION(S): Randomized to fresh or thawed ET.
      MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per transfer. RESULT(S): The
      clinical pregnancy rate per transfer was 84.0% in the cryopreservation group and
      54.7% in the fresh group. The implantation rates were 70.8% and 38.9%,
      respectively. The ongoing pregnancy rates per transfer (at 10 weeks' gestation)
      were 78.0% and 50.9%, respectively. The attributable risk percentage of
      implantation failure due to reduced endometrial receptivity in the fresh group
      was 64.7%. CONCLUSION(S): The clinical pregnancy rate per transfer was
      significantly greater in the cryopreservation group than in the fresh group.
      These results strongly suggest impaired endometrial receptivity in fresh ET
      cycles after ovarian stimulation, when compared with FET cycles with artificial
      endometrial preparation. Impaired endometrial receptivity apparently accounted
      for most implantation failures in the fresh group. ClinicalTrials.gov Identifier:
      NCT00963625.

PMID- 21737073
TI  - Evaluation of serum antimullerian hormone and inhibin B concentrations in the
      differential diagnosis of secondary oligoamenorrhea.
AB  - OBJECTIVE: To evaluate the performance of antimullerian hormone (AMH) and inhibin
      B as ovarian function markers for differentiating common causes of secondary
      oligoamenorrhea, namely hypogonadotrophic hypogonadism (HH), polycystic ovary
      syndrome (PCOS), premature ovarian failure (POF), and hyperprolactinemia (HPRL).
      DESIGN: Retrospective analysis. SETTING: Two university hospitals. PATIENT(S): A
      total of 124 women with secondary oligoamenorrhea and 26 women with normal
      ovulation. INTERVENTION(S): Serum samples from the subjects were analyzed for AMH
      and inhibin B. MAIN OUTCOME MEASURE(S): Serum AMH and inhibin B concentrations.
      RESULT(S): Serum AMH concentration was significantly raised in women having World
      Health Organization group 2 anovulation, either with or without PCOS, and was
      significantly decreased to very low levels in POF; the diagnostic accuracy in
      both conditions was excellent, with areas under the receiver operating
      characteristic curve (AUC) of 0.913 and 0.977, respectively. The discriminatory
      performance between HH and PCOS was also good, with AUC 0.861. AMH remained
      unchanged in HH and HPRL compared with ovulatory control subjects. There were
      large overlap of serum inhibin B levels in the different conditions, and a
      significant difference from control subjects existed only in the POF group.
      CONCLUSION(S): Serum AMH, but not inhibin B concentration, serves as a useful
      diagnostic tool in the differential diagnosis of secondary oligoamenorrhea.

PMID- 21737074
TI  - A cohort study to evaluate the effectiveness of laparoscopic-guided local
      injection of etoposide in the management of women with unruptured tubal
      pregnancy.
AB  - OBJECTIVE: To assess the feasibility of laparoscopic-guided local injection of
      etoposide or methotrexate (MTX) in the management of unruptured tubal pregnancy
      and compare the effectiveness of the two regimens. DESIGN: Retrospective cohort
      study. SETTING: Medical center. PATIENT(S): Thirty-one women with
      laparoscopically diagnosed unruptured tubal pregnancy. INTERVENTION(S): A regimen
      of etoposide 50 mg via laparoscopic-guided local injection (n = 17) compared with
      a conventional MTX 50 mg regimen (n = 11), after 3 patients were excluded (2
      refusals and 1 with salpingostomy). MAIN OUTCOME MEASURE(S): Serial serum beta
      hCG levels and the success rate in both groups. RESULT(S): General
      characteristics of the patients were similar in both groups. The overall success
      rate was 96.4% (27 of 28). The duration between treatment and nadir of serum beta
      hCG level (<5 mIU/mL) was significantly shorter in the etoposide group than in
      the MTX group (19.7 +/- 13.0 days vs. 33.4 +/- 8.1 days). No patient in the
      etoposide group and only 1 in the MTX group needed reintervention, which led to
      100% and 91% success rates for the etoposide and MTX groups, respectively. Three
      women in the etoposide group had subsequently successful term deliveries.
      CONCLUSION(S): Both regimens-etoposide 50 mg and MTX 50 mg via laparoscopic
      guided local injection-were acceptable in the management of women with unruptured
      tubal pregnancy because of their similar and high success rates. More studies are
      needed to confirm this observation.

PMID- 21737075
TI  - False-positive EUS-guided FNA cytology for solid pancreatic lesions.
AB  - BACKGROUND: The currently accepted paradigm is that the false-positive (FP) rate
      for EUS-guided fine-needle aspiration (EUS-FNA) cytologic analysis of a
      pancreatic lesion is less than 1%. OBJECTIVE: To assess the FP rate of EUS-FNA in
      patients who underwent surgical resection for presumed pancreatic cancer. DESIGN:
      Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: This study
      involved 367 patients with solid pancreatic lesions in whom EUS-FNA cytology
      results were interpreted as positive or suspicious for malignancy, which resulted
      in subsequent surgical resection. INTERVENTION: Surgical resection. MAIN OUTCOME
      MEASUREMENTS: The FP diagnosis was defined as EUS-FNA cytology specimens being
      reported as "positive" or "suspicious for malignancy" but that were later proven
      to be benign on surgical pathology. RESULTS: The FP rate for EUS-FNA was 4 of 367
      (1.1%) when only "positive" cytology findings were interpreted as malignant and
      14 of 367 (3.8%) when both suspicious and positive cytology findings were
      interpreted as malignant. Among the 4 cases falsely interpreted as positive, 1
      was falsely diagnosed cytologically as a neuroendocrine tumor and 3 as
      adenocarcinomas. All FP specimens showed chronic pancreatitis on surgical
      pathology. The incidence of discordance between cytology and surgical pathology
      did not change over time (2000-2006: 8/188 [4.3%] vs 2007-2010: 6/179 [3.4%]; P =
      .79). LIMITATIONS: Retrospective study at a single center. CONCLUSION: In a
      retrospective cohort trial, the FP rate for EUS-FNA of solid pancreatic lesions
      was 1.1%. Findings of the current study are in line with previous studies that
      have evaluated the FP cytology rates with EUS-FNA of solid lesions. FP cases
      transpired primarily as a result of cytologic misinterpretation in the setting of
      chronic pancreatitis.

PMID- 21737076
TI  - Role of single-operator peroral cholangioscopy in the diagnosis of indeterminate
      biliary lesions: a single-center, prospective study.
AB  - BACKGROUND: Currently available techniques to diagnose indeterminate biliary
      lesions have many limitations. OBJECTIVE: To assess the accuracy of single
      operator peroral cholangioscopy by using the SpyGlass system to differentiate
      malignant from benign disease in patients with indeterminate biliary lesions.
      DESIGN: Prospective, single-arm, single-center study. SETTING: Tertiary referral
      center. PATIENTS: Thirty-six patients with indeterminate biliary strictures and
      filling defects who had inconclusive results on previous biliary ductal tissue
      sampling. INTERVENTIONS: SpyGlass cholangioscopy with cholangioscopically guided
      intraductal biopsies. MAIN OUTCOME MEASUREMENTS: Accuracy of SpyGlass visual
      impression and SpyBite biopsies for differentiating malignant from benign ductal
      lesions. RESULTS: Thirty-six patients (22 men, mean age 48.3 years [range 27-68
      years]) with indeterminate stricture and/or filling defects underwent SpyGlass
      cholangioscopy. Of the 22 patients with a final diagnosis of malignant lesion,
      cholangioscopic impression was malignant in 21 patients (95%) and benign in 1
      patient (5%). Of the 14 patients with a final diagnosis of benign disease,
      including the 3 patients with common bile duct stones and no stricture,
      cholangioscopic impression was malignant in 3 patients (21%) and benign in 11
      patients (79%). The overall accuracy of SpyGlass visual impression for
      differentiating malignant from benign ductal lesions was 89% (32/36). The
      accuracy of SpyBite biopsies for differentiating malignant from benign ductal
      lesions that were inconclusive on ERCP-guided brushing or biopsy was 82% (27/33)
      in an intent-to-treat analysis. LIMITATIONS: No randomized comparison with
      alternative diagnostic modalities for the nature of biliary strictures.
      CONCLUSIONS: SpyGlass cholangioscopy with SpyBite biopsies has a high accuracy
      with regard to confirming or excluding malignancy in patients with indeterminate
      biliary lesions.

PMID- 21737077
TI  - Impact of nasogastric lavage on outcomes in acute GI bleeding.
AB  - BACKGROUND: Nasogastric lavage (NGL) is often performed early in the management
      of GI bleeding. This practice assumes that NGL results can assist with timely
      risk stratification and management. OBJECTIVE: We performed a retrospective
      analysis to test whether NGL is associated with improved process measures and
      outcomes in GI bleeding. DESIGN: Propensity-matched retrospective analysis.
      SETTING: University-based Veterans Affairs medical center. PATIENTS: A total of
      632 patients admitted with GI bleeding. MAIN OUTCOME MEASUREMENTS: Thirty-day
      mortality rate, length of hospital stay, transfusion requirements, surgery, and
      time to endoscopy. RESULTS: Patients receiving NGL were more likely to take
      nonsteroidal anti-inflammatory drugs and be admitted to intensive care, but less
      likely to have metastatic disease or tachycardia, be taking warfarin, or present
      on weekdays. After propensity matching, NGL did not affect mortality (odds ratio
      [OR] 0.84; 95% confidence interval [CI], 0.37-1.92), length of hospital stay (7.3
      vs 8.1 days, P = .57), surgery (OR 1.51; 95% CI, 0.42-5.43), or transfusions (3.2
      vs 3.0 units, P = .94). However, NGL was associated with earlier time to
      endoscopy (hazard ratio 1.49; 95% CI, 1.09-2.04), and bloody aspirates were
      associated high-risk lesions (OR 2.69; 95% CI, 1.08-6.73). LIMITATIONS:
      Retrospective design. CONCLUSIONS: Performing NGL is associated with the earlier
      performance of endoscopy, but does not affect clinical outcomes. Performing NGL
      at initial triage may promote more timely process of care, but further studies
      will be needed to confirm these findings.

PMID- 21737078
TI  - A commentary on the paper titled "protease activity in the multi-layered intra
      luminal thrombus of abdominal aortic aneurysms" for Atherosclerosis.

PMID- 21737079
TI  - Fabrication of graphene/poly(methyl methacrylate) composite electrode for
      capillary electrophoretic determination of bioactive constituents in Herba
      Geranii.
AB  - This report describes the development and application of a novel
      graphene/poly(methyl methacrylate) composite electrode as a sensitive
      amperometric detector of capillary electrophoresis. The composite electrode was
      fabricated on the basis of the in situ polymerization of a mixture of graphene
      and prepolymerized methyl methacrylate in the microchannel of a piece of fused
      silica capillary under heat. SEM, XRD and FT-IR offered insights into the nature
      of the composite. The results indicated that graphenes were well dispersed in the
      composite to form an interconnected conducting network. The performance of this
      unique graphene-based detector has been demonstrated by separating and detecting
      seven naturally occurring phenolic compounds in Herba Geranii in combination with
      capillary electrophoresis. The graphene-based detector offered significantly
      lower operating potentials, substantially enhanced signal-to-noise
      characteristics, and lower expense of operation. The simplicity and significant
      performance exhibited by the graphene/poly(methyl methacrylate) composite
      electrode also indicate great promise for microchip CE, flowing injection
      analysis, and other microfluidic analysis systems.

PMID- 21737080
TI  - Characterization of small interfering RNA by non-denaturing ion-pair reversed
      phase liquid chromatography.
AB  - Small interfering RNAs (siRNA) are emerging as a novel therapeutic modality for
      the specific inhibition of target gene expression. siRNA are typically formed by
      annealing of two complementary single stranded oligoribonucleotides. Compared to
      purity determination of non-hybridized single strands by denaturing
      chromatographic methods, characterization of the hybridized duplex is
      challenging. Here we are reporting a non-denaturing ion pairing-reversed phase
      (IP-RP) chromatography method capable of separating optimal duplex (full-length
      single strands only) from non-optimal duplex variants (containing shortmers,
      longmers and 2',5'-isomers) using ultraviolet- and mass spectrometric detection.
      The impact of different annealing conditions on siRNA composition was
      investigated. Optimized annealing conditions lead to a significant increase in
      optimal duplex, while total duplex content remained constant. The non-denaturing
      method reported herein showed high mass spectrometric sensitivity and superior
      separation efficiencies compared to other IP-RP buffer systems. The method is
      useful for in-process control and release testing of therapeutic double stranded
      nucleic acids such as siRNA.

PMID- 21737081
TI  - Dispersive derivatization liquid-liquid extraction of degradation
      products/precursors of mustards and V-agents from aqueous samples.
AB  - A new derivatization and extraction technique termed as dispersive derivatization
      liquid-liquid extraction (DDLLE) speeds up the analysis process by removing the
      requirement for drying of the sample. The derivatization process takes place at
      the interface between the analyte containing aqueous phase and derivatization
      agent laden organic phase. The organic phase is highly dispersed using disperser
      solvent so that the total surface area is large. The derivatizing agent used is 1
      (heptafluorobutyryl)imidazole and the resulting heptafluorobutyryl (HFB)
      derivatized analytes are partitioned into the organic phase. In addition to
      reduced sample preparation time, for some of the analytes, the HFB derivatives
      provide better spectral differentiation between isomers than conventional
      trimethylsilyl (TMS) derivatives. Method parameters for the DDLLE, such as
      extraction, and disperser solvent and their volume, type and amount of base,
      amount of heptafluorobutyrylimidazole and extraction time were optimized on
      diisopropylaminoethanol (DiPAE), ethyldiethanolamine (EDEA), triethanolamine
      (TEA) and thiodiglycol (TDG). The DDLLE was also used on various real world
      samples, which also includes few OPCW organized proficiency test and a spiked
      urine sample. The observed limit of detection (LOD) with 1mL of sample for DDLLE
      in full scan with AMDIS was 10ng/mL and with methane chemical ionization,
      multiple reaction monitoring (MRM) was 100pg/mL, i.e., 100fg on-column.

PMID- 21737082
TI  - Direct determination of 2,4,6-tricholoroanisole in wines by single-drop ionic
      liquid microextraction coupled with multicapillary column separation and ion
      mobility spectrometry detection.
AB  - This article evaluates the capability of single drop ionic liquid microextraction
      coupled with multicapillary column (MCC) and ion mobility spectrometry (IMS) for
      the determination of 2,4,6-trichloroanisole (2,4,6-TCA) in wines. The proposed
      methodology permits the direct analysis of the samples without any additional
      treatment other than dilution. This is achieved thanks to the selectivity
      provided by the ionic liquid selected as extractant, 1-hexyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)-imide, as well as the response of the analyte in the
      IMS working in negative ionization mode. Moreover, the multicapillary column
      avoids the interference of ethanol in the ion mobility spectra. The analysis of
      the sample takes ca. 35 min to be completed. The limit of detection was low as
      0.01 ng L(-1) using 2 mL of wine sample. Different calibration curves were
      constructed using aqueous standards, red and white wines, being the signals
      comparable, with an RSD similar to the method variability. Finally, a set of
      samples of different nature and packed in different containers were analysed. It
      was found than those with cork stoppers presented the highest concentration of
      2,4,6-TCA.

PMID- 21737083
TI  - Retention and selectivity of stationary phases for hydrophilic interaction
      chromatography.
AB  - More and more polar stationary phases have become available for the separation of
      small polar compounds in the past decade as hydrophilic interaction
      chromatography (HILIC) continues to find applications in new fields (e.g.,
      metabolomics and proteomics). Bare silica phases remain popular, especially in
      the bio-analytical area. A wide range of functional groups (e.g., amino, amide,
      diol, sulfobetaine, and triazole) have been employed as polar stationary phases
      for HILIC separation. This review provides a survey of the popular stationary
      phases commercially available and discusses the retention and selectivity
      characteristics of the polar stationary phases in HILIC. The purpose of the
      review is not to provide a comprehensive overview of literature reports, but
      rather focuses on findings that demonstrate retention and selectivity of the
      polar stationary phases in HILIC.

PMID- 21737084
TI  - Measurement of phospholipids by hydrophilic interaction liquid chromatography
      coupled to tandem mass spectrometry: the determination of choline containing
      compounds in foods.
AB  - A hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC
      LC-MS/MS) method using multiple scan modes was developed to separate and quantify
      11 compounds and lipid classes including acetylcholine (AcCho), betaine (Bet),
      choline (Cho), glycerophosphocholine (GPC), lysophosphatidylcholine (LPC),
      lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphocholine (PCho)
      and sphingomyelin (SM). This includes all of the major choline-containing
      compounds found in foods. The method offers advantages over other LC methods
      since HILIC chromatography is readily compatible with electrospray ionization and
      results in higher sensitivity and improved peak shapes. The LC-MS/MS method
      allows quantification of all choline-containing compounds in a single run. Tests
      of method suitability indicated linear ranges of approximately 0.25-25 MUg/ml for
      PI and PE, 0.5-50 MUg/ml for PC, 0.05-5 MUg/ml for SM and LPC, 0.5-25 MUg/ml for
      LPE, 0.02-5 MUg/ml for Cho, and 0.08-8 MUg/ml for Bet, respectively. Accuracies
      of 83-105% with precisions of 1.6-13.2% RSD were achieved for standards over a
      wide range of concentrations, demonstrating that this method will be suitable for
      food analysis. 8 polar lipid classes were found in a lipid extract of egg yolk
      and different species of the same class were differentiated based on their
      molecular weights and fragment ion information. PC and PE were found to be the
      most abundant lipid classes consisting of 71% and 18% of the total phospholipids
      in egg yolk.

PMID- 21737085
TI  - Acrylate ester-based monolithic columns for capillary electrochromatography
      separation of triacylglycerols in vegetable oils.
AB  - A simple and reliable method for the evaluation of triacylglycerols (TAGs) in
      vegetable oils by capillary electrochromatography (CEC) with UV-Vis detection,
      using octadecyl acrylate (ODA) ester-based monolithic columns, has been
      developed. The percentages of the porogenic solvents in the polymerization
      mixture, and the mobile phase composition, were optimized. The optimum monolith
      was obtained at the following ratios: 40:60% (wt/wt) monomers/porogens, 60:40%
      (wt/wt) ODA/1,3-butanediol diacrylate and 23:77% (wt/wt) 1,4-butanediol/1
      propanol (14 wt% 1,4-butanediol in the polymerization mixture). A satisfactory
      resolution between TAGs was achieved in less than 12 min with a 65:35 (v/v)
      acetonitrile/2-propanol mixture containing 5 mM ammonium acetate. The method was
      applied to the analysis of TAGs of vegetable oil samples. Using linear
      discriminant analysis of the CEC TAG profiles, the vegetable oils belonging to
      six different botanical origins (corn, extra virgin olive, hazelnut, peanut,
      soybean and sunflower) were correctly classified with an excellent resolution
      among all the categories.

PMID- 21737086
TI  - Modified Equilibrium-Dispersive Model for the interpretation of the efficiency of
      columns packed with core-shell particle.
AB  - A modified Equilibrium Dispersive (ED) Model is proposed for the modeling of
      chromatographic processes in columns packed with shell-particle adsorbents and
      operated under very high pressures. This new model was validated on the basis of
      experimental results obtained with 2.1 mm * 150 mm columns packed with
      superficially porous 1.7 MUm Kinetex-C(18) particles and with classical columns
      packed with 1.7 MUm BEH-C(18) fully porous particles. The influence of the heat
      friction on the performance of these columns was analyzed by comparing the
      experimental and calculated peak profiles. Moreover a theoretical analysis of the
      influence the solid-core conductivity on the column efficiency was discussed.

PMID- 21737087
TI  - Two-dimensional liquid chromatography separation of peptides using reversed
      phase/weak cation-exchange mixed-mode column in first dimension.
AB  - Selection of a first-dimensional separation method is very important in proteomic
      studies performed with two-dimensional liquid chromatography (2D-LC), since
      reversed-phase chromatography (RPLC) is usually chosen as the second-dimensional
      separation method in most studies. In this paper, we assess the potential use of
      mixed-mode reversed-phase/weak cation-exchange (RP/WCX) chromatography in 2D-LC
      proteomic studies. First, a new RP/WCX mixed-mode stationary phase (named C18WCX)
      was synthesized based on the polar-copolymerized approach, and a C18WCX column
      with separation efficiency comparative to conventional C18 columns was developed.
      This new mixed-mode column primarily provides hydrophobic interactions under
      acidic condition, but can offer hydrophobic and cation-exchange interactions
      under neutral and weak basic conditions. An off-line 2D-RP/WCX-RPLC system was
      established using the C18WCX column with a mobile phase of pH 6.5 in the first
      dimension and a C18 column with a mobile phase of pH 3.0 in the second dimension.
      The orthogonality of this two-dimensional system, evaluated through the
      separation of 123 tryptic peptides, was shown to be higher than that of the
      conventional 2D-RP-RPLC approach. Applying this 2D-LC method to rat brain
      samples, we identified 1031 proteins and 4397 unique peptides. In addition, this
      new two-dimensional method improved the identification of basic peptides.
      Therefore, we propose that this novel 2D-RP/WCX-RPLC system can be used as an
      alternative approach for the two-dimensional separation of peptides.

PMID- 21737088
TI  - Enantiomeric separation of (R, S)-naproxen by recycling high speed counter
      current chromatography with hydroxypropyl-beta-cyclodextrin as chiral selector.
AB  - Recycling high speed counter-current chromatography (HSCCC) was successfully
      applied to resolution of (R, S)-naproxen (NAP) using hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) as chiral selector. The two-phase solvent system
      composed of n-hexane-ethyl acetate-0.1 mol L(-1) phosphate buffer solution with
      pH=2.67 (8:2:10, v/v/v) was selected. Influence factors for the chiral separation
      process were investigated, including concentration of HP-beta-CD, equilibrium
      temperature and pH of aqueous phase. Suitable elution mode was selected for HSCCC
      enantioseparation of (R, S)-NAP. Under optimum separation conditions, 29 mg of
      (R, S)-NAP was separated using preparative recycling HSCCC with the molar ratio
      HP-beta-CD/NAP racemate 83:1. Technical details for recycling elution mode were
      discussed as for chiral HSCCC separation. The purities of both (S)-NAP and (R)
      NAP were over 99.5% as determined by HPLC. Enantiomeric excess of (S)-NAP and (R)
      NAP reached 99.4%. Recovery for NAP enantiomers from HSCCC fractions was 82-89%,
      yielding 13 mg of (S)-NAP and 12 mg of (R)-NAP.

PMID- 21737089
TI  - The frontiers of mass spectrometry-based techniques in food allergenomics.
AB  - In the last years proteomic science has started to provide an important
      contribution to the disclosure of basic aspects of food-related diseases. Among
      these, the identification of proteins involved in food allergy and their
      mechanism of activation of toxicity. Elucidation of these key issues requires the
      integration of clinical, immunological, genomic and proteomic approaches. These
      combined research efforts are aimed to obtain structural and functional
      information to assist the development of novel, more reliable and powerful
      diagnostic protocols alternative to the currently available procedures, mainly
      based on food challenge tests. Another crucial aspect related to food allergy is
      the need for methods to detect trace amounts of allergenic proteins in foods.
      Mass spectrometry is the only non-immunological method for high-specificity and
      high-sensitivity detection of allergens in foods. Nowadays, once provided the
      appropriate sample handling and the correct operative conditions, qualitative and
      quantitative determination of allergens in foods and ingredients can be
      efficiently obtained by MALDI-TOF-MS and LC-MS/MS methods, with limits of
      detection and quantification in the low-ppb range. The availability of accurate
      and fast alternatives to immunological ELISA tests may also enable the
      development of novel therapeutic strategies and food processing technologies to
      aid patients with food allergy or intolerance, and to support allergen labelling
      and certification processes, all issues where the role of proteomic science is
      emerging.

PMID- 21737090
TI  - Separation of 18alpha(H)-, 18beta(H)-oleanane and lupane by comprehensive two
      dimensional gas chromatography.
AB  - 18alpha(H)-, 18beta(H)-oleanane and lupane are angiosperm-derived biomarkers that
      are used as age indicators for the Late Cretaceous onwards when the first
      proliferation of angiosperms occurred. In addition, the 18alpha(H)-/18beta(H)
      oleanane ratio is employed as a thermal maturity parameter of crude oil. However,
      evidence has shown that accurate quantification of these compounds has been
      impeded by inadequate chromatographic separation by traditional one-dimensional
      gas chromatography. In this study, we present the separation of 18alpha(H)-,
      18beta(H)-oleanane and lupane with comprehensive two-dimensional gas
      chromatography (GC*GC). Furthermore, it was observed that 18beta(H)-oleanane
      elutes earlier than 18alpha(H)-oleanane in second dimension (polarity) which we
      attribute to steric hindrance effects. Two GC conditions have been developed in
      order to achieve baseline separation of the triterpenoids of interest in complex
      mixtures such as sediment extracts and crude oils.

PMID- 21737091
TI  - Coalescence of particle-laden drops with a planar oil-water interface.
AB  - The coalescence mechanism of a particle-laden drop resting at an oil-water
      interface has been studied. Two mechanisms for drop coalescence are observed; (i)
      complete coalescence, in which the drop experiences total coalescence in one
      event, and (ii) partial coalescence, where a drop is observed to separate during
      coalescence, producing a smaller secondary drop that rebounds and comes to rest
      at the planar oil-water interface. For particle-laden drops of approximately 4mm
      in diameter, we show the critical condition for partial to complete coalescence
      to be dependent on the particle concentration, and the interparticle interaction
      energy. Colloidal silica spheres dispersed in 10(-4) M KNO(3) electrolyte
      solution are highly charged and remain dispersed in the drop. By increasing the
      solids concentration, we measure the transition from partial to complete
      coalescence at 20 wt.%. However, this critical condition can be reduced by
      increasing the interparticle interaction energy. In 1 M KNO(3) electrolyte
      solution, the particle surface charge is sufficiently screened such that particle
      clusters readily form in the water drop. With particle clustering, transition
      from partial to complete coalescence is measured at 8 wt.% solids.

PMID- 21737092
TI  - Preparation of MCM-41 incorporated with lacunary Keggin polyoxometalate and its
      catalytic performance in esterification.
AB  - The ordered mesoporous MCM-41 materials incorporated with lacunary
      polyoxometalate were prepared via an original direct synthesis method. As the
      control, the samples with similar lacunary polyoxometalate loadings were also
      prepared by impregnation of MCM-41. The prepared samples were characterized by
      XRF, XRD, FT-IR, Raman spectra, HRTEM, SEM, N(2) adsorption isotherm, TG-DTA, and
      NH(3)-TPD technology. The results show that the lacunary polyoxometalate is
      better dispersed in the direct synthesized samples than in the impregnated
      samples, and its structure remains intact after formation of the materials. The
      catalytic performance of the materials was tested using the esterification of n
      butanol with acetic acid. The direct synthesized samples display excellent
      catalytic performance and reusability, which is superior to the impregnated
      samples. Under the optimized conditions, the conversion of n-butanol is 89.7%,
      and the selectivity of butyl acetate is nearly 100%.

PMID- 21737093
TI  - Expression of matrix metalloproteinase-9 and -12 in porcine lung infections.
AB  - Matrix metalloproteinases (MMPs) play a variety of roles during organogenesis, in
      the immune response and during acute and chronic diseases as well as in tissue
      remodelling. During the last decade, the pig has become used increasingly as a
      model for human diseases; however, studies on the expression of porcine MMPs are
      limited. In the present study species-specific antibodies were produced to
      investigate the expression of MMP-9 and MMP-12 immunohistochemically in lungs
      from pigs infected with Actinobacillus pleuropneumoniae, Pasteurella multocida
      and Staphylococcus aureus. The immunolabelling of lung tissues (one infected and
      one control pig representing each infection) was evaluated for cellular
      distribution and intensity, which was scored semiquantitatively. When compared
      with healthy, non-infected controls, the expression of both MMP-9 and MMP-12 was
      higher in infected lungs. The highest expressions were seen in the alveolar
      epithelium (MMP-9) and alveolar macrophages (MMP-12). These results are in
      accordance with studies of human lungs.

PMID- 21737094
TI  - Nitric oxide increases lysine 48-linked ubiquitination following arterial injury.
AB  - BACKGROUND: Proteins are targeted for degradation by the addition of a
      polyubiquitin chain. Chains of ubiquitin linked via lysine 48 (K48) are
      associated with protein degradation while chains linked via lysine 63 (K63) are
      associated with intracellular signaling. We have previously shown that nitric
      oxide (NO) inhibits neointimal hyperplasia in association with increasing the
      ubiquitination and degradation of UbcH10. The aim of this study is to
      characterize the effect of arterial injury and NO on K48- or K63-linked
      ubiquitination of cellular proteins. METHODS: The rat carotid artery balloon
      injury model was performed. Treatment groups included uninjured, injury alone,
      injury + proline NONOate (PROLI/NO), and PROLI/NO alone. Arteries were harvested
      at designated time points and sectioned for immunohistochemical analysis of K48-
      and K63-linked ubiquitination or homogenized for protein analysis. Vascular
      smooth muscle cells (VSMC) harvested from rat aortae were exposed to the NO donor
      diethylenetriamine NONOate (DETA/NO). Protein expression was determined by
      Western blot analysis, or immunoprecipitation and Western blot analysis. RESULTS:
      Arterial injury increased K48-linked ubiquitination in vivo. The addition of
      PROLI/NO following injury caused a further increase in K48-linked ubiquitination
      at 1 and 3 d, however, levels returned to that of injury alone by 2 wk.
      Interestingly, treatment with PROLI/NO alone increased K48-linked ubiquitination
      in vivo to levels similar to injury alone. There were lesser or opposite changes
      in K63-linked ubiquitination in all three treatment groups. DETA/NO increased K48
      linked ubiquitination in VSMC in vitro but had minimal effects on K63-linked
      ubiquitination. Low doses of DETA/NO decreased K48-linked ubiquitination of
      cyclin A and B, while high doses of DETA/NO increased K48-linked ubiquitination
      of cyclin A and B. Minimal changes were seen in K63-linked ubiquitination of
      cyclin A and B in vitro. CONCLUSIONS: Arterial injury and NO increased K48-linked
      ubiquitination in vivo and in vitro. Remarkably, minimal changes were seen in K63
      linked ubiquitination. These novel findings provide important insights into the
      vascular biology of arterial injury and suggest that one mechanism by which NO
      may prevent neointimal hyperplasia is through regulation of protein
      ubiquitination.

PMID- 21737095
TI  - Variability in gastroschisis management: a survey of North American pediatric
      surgery training programs.
AB  - BACKGROUND: The optimal surgical management of gastroschisis has yet to be
      determined. We sought to define the practice patterns in the management of
      gastroschisis, and to ascertain the degree of variability among and within
      pediatric surgical training programs. MATERIALS AND METHODS: An electronic survey
      was sent to all second-year residents in ACGME-accredited pediatric surgery
      programs in the United States and Canada. The questionnaire evaluated operative
      strategies, pain control, complications, and adherence to institutional
      protocols. RESULTS: Of the 38 pediatric surgical training programs, 27 second
      year residents (71%) completed the survey. An institutional protocol was utilized
      in only one program, and 70% reported treatment variability among faculty.
      Attempted primary closure was the treatment of choice in 76% of centers, and
      routine silo placement at 24%. The location for routine silo placement was in the
      neonatal intensive care unit (77%), operating room (22%), and delivery room (1%).
      General anesthesia was used for all primary closures, while silos were placed
      using intravenous sedation at 36% of centers. The most frequent silo-related
      complication was dislodgement, reported by 80%. Other preformed silo
      complications included the inability to achieve primary fascial closure (27%) and
      intestinal injury (27%). When entering clinical practice, 74% of trainees stated
      that they would first attempt primary closure, while 22% favored routine
      placement of a preformed silo. CONCLUSIONS: Protocol-driven care of infants with
      gastroschisis is rare in pediatric surgery training centers, leading to great
      variability in care between institutions, as well as among faculty within single
      programs. Data-driven protocols may improve care of infants with gastroschisis.

PMID- 21737096
TI  - Alcohol is associated with a lower pneumonia rate after traumatic brain injury.
AB  - BACKGROUND: Recent evidence supports the beneficial effect of alcohol on patients
      with traumatic brain injury (TBI). Pneumonia is a known complication following
      TBI; thus, the purpose of this study was to evaluate the effects of alcohol on
      pneumonia rates following moderate to severe TBI. METHODS: From 2005 to 2009, the
      Los Angeles County Trauma Database was queried for all patients >= 14 y of age
      with isolated moderate to severe TBI and admission serum alcohol levels. The
      incidence of pneumonia was compared between TBI patients with and without a
      positive blood alcohol concentration (BAC) level. The study population was then
      stratified into four BAC levels: None (0 mg/dL), low (0-100 mg/dL), moderate (100
      230 mg/dL), and high (>= 230 mg/dL). Pneumonia rates were compared across these
      levels. RESULTS: A total of 3547 patients with isolated, moderate to severe TBI
      were evaluated. Nearly 66% tested positive for alcohol. The pneumonia rate was
      significantly lower in the TBI patients who tested positive for alcohol (2.5%)
      compared with those who tested negative (4.0%, P = 0.017). The pneumonia rate
      also decreased across increasing BAC levels (linear trend P = 0.03). After
      logistic regression analysis, a positive ethanol (ETOH) level was associated with
      a reduced incidence of pneumonia (AOR = 0.62; 95%CI: 0.41-0.93; P = 0.020).
      CONCLUSION: A positive serum alcohol level was associated with a significantly
      lower pneumonia rate in isolated, moderate to severe TBI patients. This may
      explain the observed mortality reduction in TBI patients who test positive for
      alcohol. Additional research is warranted to investigate the potential
      therapeutic implications of this association.

PMID- 21737097
TI  - Assessment of Colon Cancer Literacy in screening colonoscopy patients: a
      validation study.
AB  - BACKGROUND: Few, if any, instruments assess disease-specific health literacy in
      colon cancer patients. We aimed to validate the Assessment of Colon Cancer
      Literacy (ACCL) compared with a standard health literacy test, the Newest Vital
      Sign (NVS). MATERIALS AND METHODS: A convenience sample of screening colonoscopy
      patients was surveyed. General health literacy was assessed with the NVS and
      colon cancer literacy with the ACCL. Contingency table analysis was performed.
      Results are frequency (proportion) or mean. RESULTS: Sixty-one subjects completed
      our survey, mean age 64 +/- 9 y, 33 (54%) were women, 28 (46%) had a college
      degree, 38 (62%) had prior colonoscopy, and 19 (31%) worked in healthcare. The
      sensitivity and specificity of NVS to identify limited colon cancer literacy was
      45.7% and 86.7%, respectively, while the sensitivity and specificity of ACCL to
      identify limited general health literacy was 91.3% and 34.2%, respectively.
      CONCLUSIONS: The ACCL is a valid, sensitive measure of health literacy.
      Furthermore, given its focus on clinically relevant content, this instrument may
      facilitate discussion of diagnosis, treatment, and prognosis with colon cancer
      patients. ACCL is a novel, valid health literacy instrument that may aid
      gastroenterologists, colorectal surgeons, and medical oncologists in optimizing
      patient education.

PMID- 21737098
TI  - A model of ex vivo perfusion of porcine donor lungs injured by gastric
      aspiration: a step towards pretransplant reconditioning.
AB  - BACKGROUND: Evidence of aspiration remains a major reason for declining donor
      lungs contributing to current organ shortage. The aim of the present ex vivo lung
      perfusion (EVLP) study was to compare lungs injured by gastric juice (GJ) with
      normal lungs. METHODS: Pigs (32.3 +/- 11.2 kg) were divided into two groups.
      Study group [GJ; n = 6] was intratracheally instilled with GJ, while sham
      bronchoscopy was performed in control group [C; n = 6]. Graft function was
      assessed during EVLP for 2 h. Oxygenation, aerodynamic, and hemodynamic
      parameters were recorded every 30 min. Wet to dry weight ratio (W/D) was
      calculated. Bronchoalveolar lavage was performed. Tissue samples were collected.
      RESULTS: Pulmonary vascular resistance was higher and pulmonary flow was lower in
      [GJ] versus [C] at T120; (P < 0.05). Mean airway pressure was higher in (P <
      0.05) and compliance was lower (P < 0.001) in [GJ]. No differences in oxygenation
      were seen between groups. W/D of left lung in [GJ] after EVLP was slightly (P <
      0.05) higher compared with the nonperfused right lung. More neutrophils were
      present in [GJ] before (P < 0.01) and after EVLP (P < 0.05). Histologic
      alterations were more prominent in [GJ], but did not worsen after EVLP.
      CONCLUSION: EVLP of injured lungs is possible for 2 h despite increased edema.
      This model could help to investigate ways to repair caustic lung injury during
      EVLP.

PMID- 21737099
TI  - An urban-rural blight? Choledocholithiasis presentation and treatment.
AB  - BACKGROUND: Exploration of urban-rural (UR) and regional differences is critical
      to developing effective healthcare delivery systems. Choledocholithiasis (CDL)
      remains a common problem with a range of therapeutic options and potentially
      severe complications. This study evaluated UR and regional differences of CDL
      presentation and treatment. We hypothesized that UR status contributes to
      differences in treatment of CDL. METHODS: This study examined patients from the
      2007 Healthcare Cost and Utilization Project dataset. Inpatient discharges and
      interventions for CDL patients were identified. UR and regional designations were
      determined from National Center for Health Statistics guidelines. Patients with
      pancreatitis or cholangitis were designated as complicated CDL (cCDL) patients.
      Interventions for CDL were classified as endoscopic, surgical, or percutaneous.
      Complex-sample proportion analyses were performed. RESULTS: A total of 111,021
      patients with CDL were identified; 81% of these patients lived in urban areas
      compared with 19% in rural areas; 61% had uncomplicated choledocholithiasis
      (uCDL) and 39% had cCDL. The overall distribution of uCDL and cCDL did not differ
      by UR status or region. A higher proportion of rural patients did not receive an
      intervention 45.1% (95%CI 41.8%-48.4%) versus urban patients 30.5% (28.8%-32.2%),
      P < 0.05. Interventions for urban patients were more likely endoscopic 87.7%
      (86.8%-88.6%) compared with rural 82.0% (79.3%-84.7%), P < 0.05. Rural patients
      were more likely to undergo surgery 10.5% (8.6%-12.4%) than urban patients 4.9%
      (4.4%-5.4%), P < 0.05. Regional variations did not impact the type of
      intervention received. CONCLUSION: Rural patients received CDL interventions less
      often and had a higher proportion of surgical interventions regardless of
      severity of presentation.

PMID- 21737100
TI  - Injury-induced changes in liver specific transcription factors HNF-1alpha and HNF
      4alpha.
AB  - BACKGROUND: The hepatic acute phase response(APR) is an organ-specific response
      to a diverse array of insults and is largely under transcriptional control. Liver
      specific transcription factors, hepatic nuclear factors (HNFs)-1alpha and 4alpha
      play important roles in maintenance of liver phenotype and function and their
      binding activity changes early after injury. However, their roles in modulation
      of the liver's response over time are not defined. MATERIALS AND METHODS: C57/BL6
      mice were anesthetized and exposed to 95 degrees C water for 10 s to create a 15%
      body surface area full-thickness burn. At specific time points, the mice were
      sacrificed. An ELISA for IL-6 was performed on serum and hepatic mRNA levels for
      fibrinogen-gamma and serum amyloid A(SAA)-3 were obtained through polymerase
      chain reaction (PCR). Transcriptional factor binding activity was assessed with
      electrophoretic mobility shift assays. RESULTS: Serum IL-6 levels peaked at 3 h
      and fibrinogen-gamma and SAA mRNA levels increased more than 6-fold at 12 h
      before returning to control levels at 48 h. The binding activity of HNF-4alpha
      and HNF-1alpha rapidly declined after injury (1.5 h) but recovered to near
      control level at 24 and 6 h, respectively. CONCLUSIONS: Changes in HNF-4alpha and
      HNF-1alpha binding occurred before changes in acute phase protein mRNA levels and
      were preceded by the peak in IL-6 levels. The rapid suppression and
      reconstitution of liver-specific transcription factor binding after injury may
      represent a mechanism that allows the normal liver phenotype to change and an
      injury-response phenotype to prevail. This mechanism in the liver's adaptive
      response to injury suggests a central role for both HNF-4alpha and HNF-1alpha in
      transcriptional regulation of the hepatic APR.

PMID- 21737101
TI  - Glucocorticoid modulates high-mobility group box 1 expression and Toll-like
      receptor activation in obstructive jaundice.
AB  - BACKGROUND: Obstructive jaundice is associated with bacterial translocation and
      inflammatory cytokine induction. It is unknown if toll-like receptors (TLRs) and
      their upstream molecule high mobility group box-1 (HMGB1) are involved in the
      pathogenetic mechanism and if glucocorticoid is effective in modulating the
      process. MATERIALS AND METHODS: A rat model of cholestasis by ligation of the
      extrahepatic bile duct (BDL) for 2 wk was created. TLRs, interferon regulatory
      factors (IRFs), IL-6, IL-8, antimicrobial peptide beta-defensin, and
      cathelicidin, as well as HMGB1 expressions were studied by using real-time
      quantitative reverse transcription-polymerase chain reaction,
      immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay
      (ELISA). Glucocorticoid treatment was applied to a group of BDL rats. RESULTS:
      Obstructive jaundice for 2 wk was associated with significant up-regulation of
      TLR1, 2, 4, 6, 7, and 9 mRNA expressions. There were significant increases of
      liver IRF5, IL-6, and beta-defensin 1 mRNA levels in the BDL rats than in the
      sham and nonoperative control rats, which were associated with significant
      increase of immunoreactive IRF5 protein staining in the nucleus of Kupffer cells
      and neutrophils. Hepatic HMGB1 expression and release into serum were
      significantly elevated in the cholestatic rats than in the sham and control rats.
      Glucocorticoid treatment significantly decreased hepatic HMGB1 expression and
      release into serum, which was associated with significantly decreased hepatic
      TLR4 mRNA expression in the cholestatic rats. CONCLUSIONS: The results indicate
      that obstructive jaundice may induce hepatic HMGB1 expression with activation of
      TLR4 and a number of downstream signaling molecules, which can be reversed by
      glucocorticoid administration.

PMID- 21737102
TI  - Characteristics of clinical sepsis reflected in a reliable and reproducible
      rodent sepsis model.
AB  - BACKGROUND: Sepsis models are frequently based on induction of peritonitis, with
      cecal ligation and puncture reflecting the prototypical model. However, there is
      an ongoing discussion about the limitations of these models due to their
      variability in progression and outcome. Since standardization is a cornerstone of
      experimental models, we aimed to develop a reliable and reproducible procedure
      for induction of peritonitis. MATERIALS AND METHODS: A human stool batch was
      processed for -80 degrees  storage. For induction of peritonitis in fluid
      resuscitated rats, a defined volume of stool suspension from this batch was
      injected intraperitoneally. For characterization of the model, physiologic and
      inflammatory changes were evaluated after sepsis induction. Survival analyses
      with the same batch were repeated in four independent experiments over a time
      period of 16 mo. RESULTS: The polymicrobial infection resulted in severe
      peritoneal inflammation with a systemic increase in cytokines. The mortality rate
      at 15 h was 29% and this was reproducible over a 16 mo time period. If antibiotic
      treatment was applied, a 50% survival was achieved. Laboratory markers indicated
      a progressive multi-organ dysfunction, while blood gas analysis showed
      respiratory compensation of a metabolic acidosis, and maintenance of PaO(2).
      Intravital microscopy of the liver revealed an impaired microcirculation. A
      decreased hemostatic potential was demonstrated by rotational thromboelastometry.
      Despite clinical recovery within 3 d, surviving animals showed laboratory and
      histologic signs of persisting inflammation even after 2 wk. CONCLUSIONS: This
      model reflects many features of human sepsis. Application of an infectious focus
      that is both quantitatively and qualitatively defined assures high
      reproducibility. Moreover, the procedure is simple and can be easily
      standardized.

PMID- 21737103
TI  - Computerized rounding reports: individualized solutions might work better.

PMID- 21737104
TI  - The involvement of Na+, K+-ATPase activity and free radical generation in the
      susceptibility to pentylenetetrazol-induced seizures after experimental traumatic
      brain injury.
AB  - Although the importance of brain trauma as risk factor for the development of
      epilepsy is well established, the mechanisms of epileptogenesis are not well
      understood. In the present study, we revealed that the injection of a
      subthreshold dose of PTZ (30 mg/Kg, i.p.) after 5 weeks of injury induced by
      Fluid Percussion Brain Injury (FPI) decreased latency for first clonic seizures,
      increased the time of spent generalized tonic-clonic seizures and
      electrocorticographic (EEG) wave amplitude. In addition, statistical analysis
      revealed that N-acetylcysteine (NAC) (100mg/kg) supplementation during 5 weeks
      after neuronal injury protected against behavioral and electrographical seizure
      activity elicited by subthreshold dose of PTZ. The supplementation of this
      antioxidant compound also protected against the Na(+),K(+)-ATPase activity
      inhibition and concomitant increase in the levels of oxidative stress markers
      (protein carbonylation and thiobarbituric acid-reactive substances-TBARS) in site
      and peri-contusional cortical tissue. In summary, the current experiments clearly
      showed that FPI model induces early posttraumatic seizures and suggest that an
      alteration in the lipid/protein oxidation, membrane fluidity, and Na(+),K(+)
      ATPase activity may be correlated with neuronal excitability, a significant
      component of the secondary injury cascade that accompanies TBI.

PMID- 21737105
TI  - In vitro profiling of endocrine disrupting potency of 2,2',4,4'
      tetrabromodiphenyl ether (BDE47) and related hydroxylated analogs (HO-PBDEs).
AB  - The potential of 2,2',4,4'-tetrabromodiphenyl ether (BDE47) and its related
      hydroxylated analogs (2'-HO-BDE28, 6-HO-BDE47, 4'-HO-BDE17, and 4'-HO-BDE49) to
      modulate estrogen/thyroid/androgen receptor-(ER, TR, AR), mediated responses were
      investigated by use of reporter gene assays. Exposure to 1 or 10 MUM, 4'-HO-BDE17
      significantly up-regulated expression of Luc, whereas other four chemicals did
      not induce Luc expression under control of the ER. Anti-estrogenic potency was
      observed for 4'-HO-BDE17 (IC50=1.14 MUM)>6-HO-BDE47 (IC50=2.65 MUM)>2'-HO-BDE28
      (IC50=9.49 MUM)>BDE47 (IC50=21.11 MUM). No anti-estrogenic effect of 4'-HO-BDE49
      was observed. Both 4'-HO-BDE17, 4'-HO-BDE49 resulted in greater responses of Luc
      expression induced by T3. BDE47, 2'-HO-BDE28, 6-HO-BDE47 did not show any effect
      on the expression of Luc induced by 5 nM T3. 6-HO-BDE47 (IC50=0.34 MUM)>4'-HO
      BDE17 (IC50=1.41 MUM)>BDE47 (IC50=3.83 MUM)>2'-HO-BDE28 (IC50=29.22 MUM)
      exhibited anti-androgenic potency, while 4'-HO-BDE49 did not show androgenic
      transcriptional activity.

PMID- 21737106
TI  - [Metastatic neurofibrosarcoma].

PMID- 21737107
TI  - Flavan-3-ols from the rhizomes of Drynaria fortunei.
AB  - One monomer flavan-3-ol, 4alpha-carboxymethyl-(+)-catechin methyl ester, two
      monomer flavan-3-ol glycosides, (+)-afzelechin-3-O-beta-allopyranoside, (+)
      afzelechin-6-C-beta-glucopyranoside, two dimer flavan-3-ols, (-)-epiafzelechin
      (4beta->8)-4beta-carboxymethyl-(-)-epicatechin methyl ester, and -(-)
      epiafzelechin-(4beta->8)-4alpha-carboxymethyl-(-)epiafzelechin ethyl ester, and
      one trimer flavan-3-ol, (-)-epiafzelechin-(4beta->8)-(-)-epiafzelechin-(4beta->8)
      4beta-carboxymethyl-(-)-epiafzelechin methyl ester, together with thirteen known
      flavan-3-ols were isolated from the rhizomes of Drynaria fortunei (Kunze) J.Sm
      (Polypodiaceae). The structures were established by analysis of their HRESIMS,
      1D, 2D NMR spectroscopic, and CD data. In order to obtain improved resolution,
      the high-resolution NMR spectra of the dimers and trimer were measured at -40 
      degrees C.

PMID- 21737108
TI  - [Nodular pseudoangiomatous stromal hyperplasia of the breast in two adolescents].
AB  - Nodular pseudoangiomatous stromal hyperplasia is a very rare benign breast lesion
      found in 0.4% of biopsies. It usually presents as a fast-growing palpable lesion
      in women between 30 and 40 years of age and is exceptionally rare in adolescents.
      Histological examination reveals a proliferation of stromal cells from connective
      tissue forming anastomosed empty pseudovascular spaces lined with myofibroblasts.
      We present the cases of two adolescents (13 and 18 years old) with fast-growing
      palpable breast nodules. Both underwent breast ultrasonography and core biopsy.
      The ultrasonographic findings of nodular pseudoangiomatous stromal hyperplasia
      were indistinguishable from those reported for juvenile fibroadenoma and for
      phyllodes tumor. Thus, histological study was required for the definitive
      diagnosis. Treatment depends on the size of the nodule. In our two patients, the
      lesion was surgically excised through tumorectomy and mastectomy.

PMID- 21737109
TI  - Expression of thyroid-specific transcription factors in thyroid carcinoma,
      contralateral thyroid lobe and healthy thyroid gland in dogs.
AB  - Thyrotropin receptor (TSH-R), thyroglobulin (Tg), thyroperoxidase (TPO), thyroid
      specific transcription factor-1 (TTF-1), paired box 8 transcription factor (PAX
      8), insulin like growth factor-1 (IGF-1) and estrogen receptor alpha (ERalpha)
      transcripts were determined by real-time PCR in follicular carcinoma and
      contralateral (CL) lobes, and healthy thyroid canine glands. Concentrations of
      TSH-R, PAX-8, and ERalpha mRNA were not different among groups; the carcinoma
      group had lower Tg and TPO mRNA than healthy and CL groups, while no differences
      were found between the two latter groups, suggesting that the carcinoma tissue
      presents an altered capacity to synthesize thyroid hormones. The transcription
      factor that promotes thyrocytes proliferation, TTF-1 as well as IGF-1, presented
      a greater mRNA expression in the CL group, suggesting that the CL lobe may
      function in a compensatory state.

PMID- 21737110
TI  - Data-loggers carried on a harness do not adversely affect sheep locomotion.
AB  - The use of externally fitted motion sensors to animal subjects has the potential
      for allowing researchers to investigate subtle changes in animal movement that
      may occur with the onset of specific diseases. However, it is crucial to consider
      whether or not the use of such technology has an effect on the variables
      measured. Here, we examine the effect of a body harness data logging device on
      the locomotive patterns of female Merino sheep, Ovis aries. We extracted
      locomotion variables typical of motion sensor data (stride frequency, stride
      length, gait type, speed, and limb velocity) from high-definition video collected
      under controlled conditions. We found no significant difference between the
      variables measured in the harnessed and unharnessed conditions. Overall, our
      experiment demonstrates that data-loggers carried on a harness do not adversely
      affect sheep locomotion, and extended periods of habituation post-instalment of
      devices should ensure consistency and accuracy of data in future experiments.

PMID- 21737111
TI  - [Posterior reversible encephalopathy syndrome and eclampsia: a descriptive study
      of 13 cases in Morocco].
AB  - INTRODUCTION: The occurrence of posterior reversible encephalopathy in eclampsia
      is a rare but known event. We propose to describe the clinical and radiological
      features and the outcome. METHODS: A retrospective study was conducted from
      January 2005 to April 2010 including all cases of posterior reversible
      encephalopathy syndrome (PRES) occurring on eclampsia in patients hospitalized in
      the obstetrical intensive care unit, University Hospital of Casablanca. RESULTS:
      Thirteen cases of PRES on eclampsia were collected, the average age was 29 years
      (18-42). Systolic pressure and diastolic blood pressure at admission were higher
      than 150 mmHg and 100 respectively in 10 cases. The signs found were: a
      regressive blindness in five patients and focal signs in four. The complications
      were thrombocytopenia in 10 patients, abnormal liver function in eight, Hellp
      syndrome in nine, and acute renal failure in two. The brain regions most commonly
      affected were the parietal and occipital areas (13 patients), followed by
      temporal regions, frontal, and basal ganglia (eight patients each). Five patients
      required assisted ventilation (AV) over 24 hours. Death complicated the outcome
      in four of our patients, but no deaths were directly attributable to PRES itself,
      and all four patients had Hellp syndrome and required AV greater than 48 hours.
      In the other patients, total regression of neurological signs was noted.
      CONCLUSION: This study emphasizes the severity of the Posterior 'reversible'
      encephalopathy syndrome on eclampsia.

PMID- 21737112
TI  - Loss of genetic diversity in Culex quinquefasciatus targeted by a lymphatic
      filariasis vector control program in Recife, Brazil.
AB  - Recife is one of the largest cities in north-eastern Brazil and is endemic for
      lymphatic filariasis transmitted by Culex quinquefasciatus. Since 2003 a control
      program has targeted mosquito larvae by elimination of breeding sites and
      bimonthly application of Bacillus sphaericus. To assess the impact of this
      program on the local vector population we monitored the genetic diversity and
      differentiation of Cx. quinquefasciatus using microsatellites and a B. sphaericus
      resistance associated mutation (cqm1(REC)) over a 3-year period. We detected a
      significant but gradual decline in allelic diversity, which, coupled with subtle
      temporal genetic structure, suggests a major impact of the control program on the
      vector population. Selection on cqm1(REC) does not appear to be involved with
      loss of neutral diversity from the population, with no temporal trend in
      resistant allele frequency and no correlation with microsatellite
      differentiation. The evidence for short-term genetic drift we detected suggests a
      low ratio of effective population size: census population size for Cx.
      quinquefasciatus, perhaps coupled with strong geographically-restricted
      population structure. Spatial definition of populations will be an important step
      for success of an expanded vector control program.

PMID- 21737113
TI  - Retention time profiling of all 136 tetra- through octa- chlorinated dibenzo-p
      dioxins and dibenzofurans on a variety of Si-Arylene gas chromatographic
      stationary phases.
AB  - The applicability of three different Silphenylene Silicone co-polymer (Si
      Arylene) GC stationary phases (J&W Scientific DB-5ms, Varian VF-5ms, and VF-Xms)
      has been evaluated for the separation of all 136 tetra- through the octa-
      chlorinated dibenzo-p-dioxins (PCDD) and chlorinated dibenzofurans (PCDF) from
      closely eluting isomers using gas chromatography/high resolution mass
      spectrometry (GC/HRMS). Their relative performance data are compared to the
      "conventional" 5% diphenyl 95% dimethylpolysiloxane GC column (Supelco Equity-5)
      and to each other based on absolute retention times, visualized mass
      chromatograms, and the separation of 2,3,7,8-substituted isomers. VF-Xms GC
      column was able to demonstrate a better performance towards separation of 2,3,7,8
      substituted PCDD/PCDF compared to other Si-Arylene GC columns tested, where only
      2,3,4,7,8-PnCDF can not be resolved from 1,2,3,6,9-PnCDF and 2,3,4,6,7,8
      /1,2,3,6,8,9-HxCDF and 1,2,3,7,8,9-/1,2,3,4,8,9-HxCDF can be at least partially
      resolved. These data suggest that the development of a single GC column for the
      separation of all 17 2,3,7,8-substituted dioxins and furans is feasible, which
      therefore could be used as a standard tool for the PCDD/PCDF methods globally
      including USEPA methods 1613b, 8290A, 8280B, European Standard Method EN 1948,
      Canadian methods DFPCB-E3418, EPS 1/RM/19, Japanese methods JIS K0311 and JIS
      K0312. Having one specific GC column to separate all 2,3,7,8-substituted
      PCDD/PCDF will significantly improve the data quality, comparability by the
      various methods and assessment techniques while simultaneously leading to a more
      cost and time efficient operation.

PMID- 21737114
TI  - Organochlorine pesticide in fresh and pasteurized cow's milk from Kampala
      markets.
AB  - Fresh and pasteurized milk samples from Kampala markets were analyzed for
      organochlorine pesticides using a gas chromatograph equipped with an electron
      capture detector. Five organochlorine pesticides, namely; aldrin, dieldrin,
      endosulfan, lindane, DDT and its metabolites were detected in the milk samples
      and confirmed with a gas chromatograph equipped with a mass spectrometer [GC-MS].
      The mean values are expressed in mgkg(-1) milk fat (mf) basis. The mean
      concentration in the fresh milk (n=54) were: 0.026 +/- 0.003 mg kg(-1) mf; 0.002
      +/- 0.0003 mg kg(-1), below the detection limit; 0.007 +/- 0.003 mg kg(-1), 0.009
      +/- 0.002 mg kg(-1) milk fat for lindane, endosulfan dieldrin and aldrin,
      respectively. The mean concentrations of p,p'-DDE; p,p'-DDT and o,p'-DDT were
      0.009 +/- 0.002 mg kg(-1); 0.033 +/- 0.007 mg kg(-1) and 0.008 +/- 0.001 mg kg(
      1) mf, respectively in the fresh milk samples. In the pasteurized milk samples
      (n=47), the mean concentrations recorded were: 0.008 +/- 0.003 mg kg(-1), 0.025
      +/- 0.004 mg kg(-1), and 0.007 +/- 0.001 mg kg(-1), respectively for p,p'-DDE;
      p,p'-DDT and o,p'-DDT. Alpha and beta-endosulfan recorded the concentration below
      the detection limit and the mean of 0.022 +/- 0.001 mg kg(-1) mf, 0.005 +/- 0.002
      mg kg(-1) mf, and 0.006 +/- 0.0002 mg kg(-1) mf, respectively for lindane,
      dieldrin and aldrin. Although, most of the residues detected were above the
      residue limits set by the FAO/WHO (2008), bioaccumulation of these residues is
      likely to pose health risks to the consumers of milk in Uganda.

PMID- 21737115
TI  - Inorganic nanoparticles enhance the production of reactive oxygen species (ROS)
      during the autoxidation of L-3,4-dihydroxyphenylalanine (L-dopa).
AB  - Public concerns over the toxicity of nanoparticles (NPs) are growing due to the
      rapid development of nanotechnology. An important mechanism of nanotoxicity is
      oxidative stress resulting from reactive oxygen species (ROS). In this study, the
      chemical production of ROS by inorganic NPs oxidizing the mammalian phenolic
      compound, L-3,4-dihydroxyphenylalanine (l-dopa) was evaluated using a ROS
      sensitive dye, 2',7'-diclorodihydrofluorescin (DCFH). CeO(2), Fe(2)O(3) and Fe(0)
      NPs enhanced ROS production during the autoxidation of L-dopa by more than four
      fold in reactions that were dependent on O(2). This is the first report of
      chemical ROS production due to interaction of phenolic compounds with NPs.
      Mn(2)O(3) oxidized DCFH in a reaction that did not require O(2) or L-dopa,
      suggesting a direct redox reaction between the Mn(2)O(3) and the dye. CeO(2),
      Mn(2)O(3) and to a lesser extent Fe(0) formed clear electron paramagnetic
      resonance (EPR) signature for hydroxyl radicals when incubated in aerobic aqueous
      suspensions with spin traps. The results indicate that NPs can generate ROS via
      chemical reactions with medium components and biomolecules susceptible to
      oxidation, such as L-dopa. NPs were reactive whereas micron-sized particles were
      not. The combined assay with L-dopa and DCFH is a method proposed to screen for
      chemical ROS production by NPs.

PMID- 21737116
TI  - Leaching of zinc from tire wear particles under simulated estuarine conditions.
AB  - Tire wear particles (TWP) abraded from end-of-life passenger car tires have been
      added at a concentration of 1 g L-1 to river water, sea water and mixtures
      thereof in order to examine the chemical controls on the leaching of Zn from the
      rubber matrix. Results of time-dependent experiments conducted over a period of 5
      days were consistent with a diffusion controlled leaching mechanism with rate
      constants of about 0.04 mg L-1 h-1/2 in river water and between about 0.02 and
      0.03 mg L-1 h-1/2 in sea water. Additional experiments revealed a reduction in Zn
      dissolution with both increasing salinity and pH and enhancement of leaching in
      the presence of fluorescent light compared with dark conditions. In corresponding
      experiments conducted in the presence of a fixed quantity (0.8 g L-1) of clean,
      fractionated estuarine sediment, aqueous Zn concentrations were reduced by at
      least an order of magnitude. Increasing the quantity of sediment resulted in a
      progressive reduction in Zn concentration until an apparent equilibrium was
      achieved, with partition coefficients defining the sediment-water distribution of
      Zn of about 550 mL g-1 and 270 mL g-1 in river water and sea water, respectively.
      Results are interpreted in terms of the dissolution of ZnO and other residual
      complexes from the matrix and the subsequent, rapid adsorption of Zn2+ ions to
      coexistent estuarine sediment. The findings of the study are discussed in terms
      of their implications for the transport, fate and effects of TWP Zn in aquatic
      environments that are likely to receive urban runoff.

PMID- 21737117
TI  - Formation of toxic species and precursors of PCDD/F in thermal decomposition of
      alpha-cypermethrin.
AB  - This article examines the thermal decomposition of alpha-cypermethrin, one of the
      most common pyrethroid pesticides. The objective was to identify its
      decomposition pathways and to gain an understanding into the formation of toxic
      species in the environment, including those that may behave in combustion
      systems, especially in fires in the environment, as precursors for PCDD/F
      (polychlorinated dibenzo-p-dioxins and dibenzofurans). The experiments were
      conducted under non-oxidative conditions using a tubular reactor housed in a
      three-zone heating furnace and operated with a dilute stream of alpha
      cypermethrin in 99.999% nitrogen. The condensable products were identified and
      quantitated, after being collected in a cold solvent trap and in an activated
      charcoal cartridge. The study revealed the formation of pollutants including
      precursors of toxic PCDD/F such as diphenyl ether and phenol. It was also found
      that the decomposition of alpha-cypermethrin involved parallel pathways of an
      unusual vinylcyclopropane rearrangement-cum-aromatisation reaction transforming
      alpha-cypermethrin and a rupture of the C(=O)O-C(-C=N) linkage. The former is
      similar to that occurring in the decomposition of permethrin pesticide, whereas
      the latter constitutes a newly discovered channel for the formation of
      pollutants. Density functional theory (DFT) calculations allowed us to attribute
      the occurrence of the second pathway to the effect of the cyanide group in
      significantly weakening the O-C bond.

PMID- 21737118
TI  - Incidence of thyroid disease following exposure to polybrominated biphenyls and
      polychlorinated biphenyls, Michigan, 1974-2006.
AB  - Thyroid hormones, which influence body metabolism and development, could be
      affected by persistent organic pollutants. We sought to examine the relationship
      between polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) and
      thyroid disease. We employed incidence density sampling to perform a nested case
      control analysis of the Michigan Long-Term PBB Cohort. Cohort members (n=3333)
      were exposed to PBBs through contaminated cattle feed in 1973-1974 and to PCBs
      through daily life. Those with detectable serum PBB and PCB concentrations at
      enrollment were categorized into tertiles of PBB and PCB exposure. Case-patients
      were cohort members answering "Yes" to "Has a healthcare provider ever told you
      that you had a thyroid problem?" during follow-up interviews; control-patients
      were cohort members answering "No". We used odds ratios (OR) with 95% confidence
      intervals (CI) to compare odds of thyroid disease by PBB and PCB exposure and by
      various risk factors. Total cumulative thyroid disease incidence after 33 years
      was 13.9% among women and 2.6% among men. After adjusting for body mass index, we
      found no statistically significant differences in odds of any type of thyroid
      disease among women or men with elevated PBB or PCB exposure. Compared to control
      patients, women with thyroid disease had increased odds of being overweight/obese
      (OR=2.82, 95% CI: 1.94-4.11) and developing infertility (OR=1.71, 95% CI: 1.08
      2.69), diabetes (OR=1.61, 95% CI: 1.04-2.51), or arthritis (OR=1.71, 95% CI: 1.18
      2.50) during follow-up. Additional research should explore potential associations
      between PBBs/PCBs and thyroid disease among children exposed in utero.

PMID- 21737119
TI  - Level and source of 129I of environmental samples in Xi'an region, China.
AB  - Iodine-129 is widely used as a tracer in various environmental practices such as
      monitoring of nuclear environmental safety, seawater exchange and transport,
      geochemical cycle of stable iodine and dating of geological events. The spatial
      distribution of (129)I concentration varies significantly on global scale because
      of anthropogenic input from nuclear activities coupled with scarcity of data on
      environmental (129)I variability in many parts of the world including Asia. Here
      we report new data on (129)I and (127)I concentrations in soil, vegetation, river
      water and precipitation collected from Xi'an area, China. The results indicate
      values for environmental (129)I/(127)I ratios in the investigated area range from
      1.1*10(-10) to 43.5*10(-10) with a mean of 20.6*10(-10), which is 1-3 orders of
      magnitude lower than the ratios observed in Europe, but comparable with those
      observed in the locations far from direct effect of point release sources and at
      similar latitude. The main source of (129)I in the investigated area is
      attributed to the global fallout of both atmospheric nuclear weapons testing and
      long distance dispersion of fuel reprocessing releases.

PMID- 21737120
TI  - Effects of climate change on the wash-off of volatile organic compounds from
      urban roads.
AB  - The predicted changes in rainfall characteristics due to climate change could
      adversely affect stormwater quality in highly urbanised coastal areas throughout
      the world. This in turn will exert a significant influence on the discharge of
      pollutants to estuarine and marine waters. Hence, an in-depth analysis of the
      effects of such changes on the wash-off of volatile organic compounds (VOCs) from
      urban roads in the Gold Coast region in Australia was undertaken. The rainfall
      characteristics were simulated using a rainfall simulator. Principal Component
      Analysis (PCA) and Multicriteria Decision tools such as PROMETHEE and GAIA were
      employed to understand the VOC wash-off under climate change. It was found that
      low, low to moderate and high rain events due to climate change will affect the
      wash-off of toluene, ethylbenzene, meta-xylene, para-xylene and ortho-xylene from
      urban roads in Gold Coast. Total organic carbon (TOC) was identified as
      predominant carrier of toluene, meta-xylene and para-xylene in <1 MUm to 150 MUm
      fractions and for ethylbenzene in 150 MUm to >300 MUm fractions under such
      dominant rain events due to climate change. However, ortho-xylene did not show
      such affinity towards either TOC or TSS (total suspended solids) under the
      simulated climatic conditions.

PMID- 21737121
TI  - Conceptual modeling for identification of worst case conditions in environmental
      risk assessment of nanomaterials using nZVI and C60 as case studies.
AB  - Conducting environmental risk assessment of engineered nanomaterials has been an
      extremely challenging endeavor thus far. Moreover, recent findings from the nano
      risk scientific community indicate that it is unlikely that many of these
      challenges will be easily resolved in the near future, especially given the vast
      variety and complexity of nanomaterials and their applications. As an approach to
      help optimize environmental risk assessments of nanomaterials, we apply the Worst
      Case Definition (WCD) model to identify best estimates for worst-case conditions
      of environmental risks of two case studies which use engineered nanoparticles,
      namely nZVI in soil and groundwater remediation and C(60) in an engine oil
      lubricant. Results generated from this analysis may ultimately help prioritize
      research areas for environmental risk assessments of nZVI and C(60) in these
      applications as well as demonstrate the use of worst-case conditions to optimize
      future research efforts for other nanomaterials. Through the application of the
      WCD model, we find that the most probable worst-case conditions for both case
      studies include i) active uptake mechanisms, ii) accumulation in organisms, iii)
      ecotoxicological response mechanisms such as reactive oxygen species (ROS)
      production and cell membrane damage or disruption, iv) surface properties of nZVI
      and C(60), and v) acute exposure tolerance of organisms. Additional estimates of
      worst-case conditions for C(60) also include the physical location of C(60) in
      the environment from surface run-off, cellular exposure routes for heterotrophic
      organisms, and the presence of light to amplify adverse effects. Based on results
      of this analysis, we recommend the prioritization of research for the selected
      applications within the following areas: organism active uptake ability of nZVI
      and C(60) and ecotoxicological response end-points and response mechanisms
      including ROS production and cell membrane damage, full nanomaterial
      characterization taking into account detailed information on nanomaterial surface
      properties, and investigations of dose-response relationships for a variety of
      organisms.

PMID- 21737122
TI  - Compositional heterogeneity may limit the usefulness of some commercial
      naphthenic acids for toxicity assays.
AB  - Naphthenic acids are considered variously as monocarboxylic acids fitting the
      formula C(n)H(2n+z)O(2) (where z is a zero or negative even integer), as only
      alicyclic (i.e. non-aromatic) monocarboxylic acids fitting this formula (z<=0),
      or simply as those carboxylic acids occurring in petroleum products or crude oils
      that have been formed through biodegradation of hydrocarbons. Such acids are
      known constituents of the process-affected water associated with some expanding
      oil sands industries, of some immature and biodegraded crude oils, of produced
      water discharges from oil production platforms and are used as biocides and as
      components in the manufacture of steel radial tyres. As a result of these
      potential vectors of the acids into the environment, various naphthenic acid
      mixtures which are available commercially have been used for a range of toxicity
      studies. However, as some manufacturers make clear, but which is not often
      emphasised in the toxicity studies, a range of different quality naphthenic acids
      is produced commercially. It has been suggested previously, and we showed
      recently and elucidate further herein, that such commercial mixtures therefore
      sometimes contain toxic components other than carboxylic acids. For example, we
      identify herein by two-dimensional comprehensive gas chromatography-mass
      spectrometry, a range of C(0-6) alkylphenols in a batch of commercial naphthenic
      acids. Since these compounds are known toxicants, the contribution of such non
      carboxylic acids, if any, to the toxicity attributed previously to the acids,
      should also be considered. This will be reflected in the concentrations and
      effective toxicities of such components. In order to establish the toxicity of
      the acids per se, assays of pure synthetic carboxylic acids of the type now known
      to be present in naphthenic acids from petroleum or oil sands may be more
      appropriate than tests of the toxicity of largely unknown, heterogeneous,
      mixtures.

PMID- 21737123
TI  - A kinetic study of Cr(VI) reduction by calcium polysulfide.
AB  - The goal of this study was to determine the influence of pH and oxygen conditions
      on the reaction kinetics of hexavalent chromium (Cr(VI)) with calcium polysulfide
      (CPS). The observed kinetic reaction rate, k(obs), between Cr(VI) and CPS was
      evaluated for the pH range 5.5-8.5, aerobic open, aerobic closed and anaerobic
      conditions, and two Cr(VI) species (aqueous and adsorbed on goethite). The
      kinetic model followed a second-order reaction rate, unlike the first-order
      reaction rate of the Cr(VI)-sulfide reaction. k(obs) increased exponentially with
      pH in the range of 8.5 to 5.5 under anaerobic conditions, while under aerobic
      conditions k(obs) had a maximum at pH 7. Qualitative sulfur analyses showed that
      thiosulfates were present at and above pH 7 in the aerobic experiments, which can
      also reduce Cr(VI). Similarly, pure CPS in the presence of oxygen yielded
      sulfides and thiosulfates, while sulfide converted to a mixture of sulfite,
      thiosulfates, sulfites and sulfates. CPS is thus likely to have a longer
      residence time and greater reducing capacity in the subsurface compared to
      sulfide at neutral and basic pH environments.

PMID- 21737124
TI  - Plasma factor VII-activating protease is increased by oral contraceptives and
      induces factor VII activation in-vivo.
AB  - Oral contraceptive (OC) use influences the hemostatic system significantly and is
      a risk factor for development of cardiovascular disease. Factor VII-activating
      protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the
      1601G/A polymorphism in the FSAP gene expresses a FSAP alloenzyme with reduced
      pro-fibrinolytic activity. Presently, we address whether OC use and OC
      formulation affect FSAP measures in human blood. Healthy women (n=588) were
      allocated to six cycles of OCs with estrogen contents of 20 MUg (n=158), 30 MUg
      (n=284), 35 MUg (n=79) or 50 MUg (n=67) combined with various progestins. FSAP
      genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline
      and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the
      women and was associated with significantly reduced levels of FSAP (P<=0.001). OC
      use increased FSAP antigen by 25% and FSAP activity by 59% (P<0.001). The FSAP
      increase was comparable in the seven different OC treatment groups (P>0.05). The
      relative increase in FSAP activity was significantly higher in women carrying the
      1601GG genotype (63%) than in women carrying 1601GA genotype (50%) (P=0.01) and
      was associated with an increased activation of FVII. IN CONCLUSION: OC use
      increases the plasma measures of FSAP. The increase in FSAP is comparable in the
      seven OC-groups studied but is more significant in women carrying the 1601GG
      genotype than in women with the 1601GA genotype and results in increased
      activation of FVII suggesting that FSAP-induced activation of FVII takes place in
      vivo and not only in-vitro as hitherto described.

PMID- 21737125
TI  - Anticoagulants and chronic kidney disease.

PMID- 21737126
TI  - Pre-analytical and analytical variables affecting the measurement of plasma
      derived microparticle tissue factor activity.
AB  - INTRODUCTION: Elevated levels of tissue factor positive (TF(+)) microparticles
      (MPs) are observed in plasma from a variety of patients with an increased risk of
      thrombosis. We and others have described the measurement of TF activity in MPs
      isolated from plasma. The aim of this study was to investigate the effects of pre
      analytical and analytical variables on TF activity of MPs isolated from blood of
      healthy volunteers either untreated or treated ex vivo with bacterial
      lipopolysaccharide. MATERIALS AND METHODS: We evaluated the following parameters:
      use of different centrifugation speeds to isolate the MPs; comparison of TF
      activity of MPs isolated from platelet poor plasma versus platelet free plasma;
      effect of freeze/thaw on MP TF activity; and comparison of the MP TF activity
      assay with the measurement of TF protein by ELISA or flow cytometry. RESULTS: MPs
      prepared from platelet poor plasma by centrifugation at 20,000*g or 100,000*g for
      15 minutes had similar levels of TF activity. However, significantly less TF
      activity was found in MPs isolated from platelet free plasma compared with
      platelet poor plasma. Interestingly, freeze/thawing of the plasma showed donor to
      donor variation in MP TF activity, with a moderate increase in some individuals.
      CONCLUSION: TF(+) MPs can be quantitatively isolated from platelet poor or
      platelet free plasma by centrifugation at 20,000*g for 15 minutes. Measurement of
      MP TF activity in plasma may be used to detect a prothrombotic state in patients
      with various diseases.

PMID- 21737127
TI  - Effects of hawthorn (Crataegus laevigata) on platelet aggregation in healthy
      volunteers.

PMID- 21737128
TI  - Whole blood gene expression analyses in patients with single versus recurrent
      venous thromboembolism.
AB  - INTRODUCTION: Venous thromboembolism may recur in up to 30% of patients with a
      spontaneous venous thromboembolism after a standard course of anticoagulation.
      Identification of patients at risk for recurrent venous thromboembolism would
      facilitate decisions concerning the duration of anticoagulant therapy.
      OBJECTIVES: In this exploratory study, we investigated whether whole blood gene
      expression data could distinguish subjects with single venous thromboembolism
      from subjects with recurrent venous thromboembolism. METHODS: 40 adults with
      venous thromboembolism (23 with single event and 17 with recurrent events) on
      warfarin were recruited. Individuals with antiphospholipid syndrome or cancer
      were excluded. Plasma and serum samples were collected for biomarker testing, and
      PAXgene tubes were used to collect whole blood RNA samples. RESULTS: D-dimer
      levels were significantly higher in patients with recurrent venous
      thromboembolism, but P-selectin and thrombin-antithrombin complex levels were
      similar in the two groups. Comparison of gene expression data from the two groups
      provided us with a 50 gene probe model that distinguished these two groups with
      good receiver operating curve characteristics (AUC 0.75). This model includes
      genes involved in mRNA splicing and platelet aggregation. Pathway analysis
      between subjects with single and recurrent venous thromboembolism revealed that
      the Akt pathway was up-regulated in the recurrent venous thromboembolism group
      compared to the single venous thromboembolism group. CONCLUSIONS: In this
      exploratory study, gene expression profiles of whole blood appear to be a useful
      strategy to distinguish subjects with single venous thromboembolism from those
      with recurrent venous thromboembolism. Prospective studies with additional
      patients are needed to validate these results.

PMID- 21737129
TI  - Psychological impact of thrombophilia testing in asymptomatic family members.
AB  - INTRODUCTION: Psychological distress and worry are commonly described as
      potential consequences of genetic screening for various disorders. Thrombophilia
      testing may be offered to asymptomatic persons with a family history of venous
      thrombosis and thrombophilia. Our objectives were to measure the psychological
      impacts of thrombophilia testing in first degree relatives and to determine if
      our intervention, a more intensive care strategy to heighten awareness of both
      risk and symptoms of thrombosis, caused psychological distress. MATERIALS &
      METHODS: First degree relatives of patients with a known thrombophilia and
      history of venous thrombosis were tested for thrombophilia. The Perceived Risk
      Questionnaire and validated psychological instruments (POMS-SF; SCL-90-R
      Somatization subscale) were administered before testing, one week after receiving
      results and a year later. Thrombophilia carriers were randomized in family
      clusters to receive Standard Care or the Intensive Care intervention. RESULTS:
      There were 100 carriers who were randomized to Standard (n=48) or Intensive Care
      (n=52) and 103 non-carriers. One week after receiving results, we did not observe
      any difference in psychological distress between carriers and non-carriers, with
      low levels overall. At 1 year, psychological distress scores were similar between
      the Standard and Intensive Care arms and did not differ from baseline.
      CONCLUSIONS: The results of this pilot study do not support the concern that
      thrombophilia screening in asymptomatic relatives triggers psychological distress
      and worry. Furthermore, our intensive educational approach did not appear to
      induce undue distress. While the positive benefits of thrombophilia screening
      remain unproven, clinicians should not be deterred from offering screening by the
      fear of causing psychological harm.

PMID- 21737130
TI  - Mosaic analysis with double markers reveals tumor cell of origin in glioma.
AB  - Cancer cell of origin is difficult to identify by analyzing cells within terminal
      stage tumors, whose identity could be concealed by the acquired plasticity. Thus,
      an ideal approach to identify the cell of origin is to analyze proliferative
      abnormalities in distinct lineages prior to malignancy. Here, we use mosaic
      analysis with double markers (MADM) in mice to model gliomagenesis by initiating
      concurrent p53/Nf1 mutations sporadically in neural stem cells (NSCs).
      Surprisingly, MADM-based lineage tracing revealed significant aberrant growth
      prior to malignancy only in oligodendrocyte precursor cells (OPCs), but not in
      any other NSC-derived lineages or NSCs themselves. Upon tumor formation,
      phenotypic and transcriptome analyses of tumor cells revealed salient OPC
      features. Finally, introducing the same p53/Nf1 mutations directly into OPCs
      consistently led to gliomagenesis. Our findings suggest OPCs as the cell of
      origin in this model, even when initial mutations occur in NSCs, and highlight
      the importance of analyzing premalignant stages to identify the cancer cell of
      origin.

PMID- 21737131
TI  - The Strength and Difficulties Questionnaire: Russian validation of the teacher
      version and comparison of teacher and student reports.
AB  - OBJECTIVE: To confirm factor structure of the teacher Strengths and Difficulties
      Questionnaire (SDQ) and to compare teacher and student reports in Russian youth.
      METHOD: The SDQ and psychopathology measures were completed by teachers in a
      representative sample of urban adolescents (N = 528). The factor structure was
      examined on two randomly selected split-halves of the sample, and using a gender
      split. The functional impairment score was predicted by the SDQ problem scales.
      RESULTS: The fit for all models was acceptable. The fit did not decrease when
      applying increasing constraints in the random-split model, but became
      significantly worse for the gender model, suggesting lack of measure invariance.
      SDQ problem scales explained 37% of functional impairment variance. Significant
      scale interaction (emotional problems*peer problems and conduct
      problems*hyperactivity) suggest that combination of these problems produces an
      additional impact on functioning. CONCLUSIONS: The SDQ teacher report may
      represent a potentially useful screener for children and youth.

PMID- 21737132
TI  - Radiology service at Great Ormond Street Hospital.

PMID- 21737133
TI  - Great Ormond Street Hospital and its management team.

PMID- 21737134
TI  - Response to correspondence on Great Ormond Street Hospital.

PMID- 21737135
TI  - Rabbit ATG for aplastic anaemia treatment: a backward step?

PMID- 21737136
TI  - Sudden unexpected death in epilepsy.
AB  - Sudden unexpected death in epilepsy (SUDEP) refers to the sudden death of a
      seemingly healthy individual with epilepsy, usually occurring during, or
      immediately after, a tonic-clonic seizure. The frequency of SUDEP varies
      depending on the severity of the epilepsy, but overall the risk of sudden death
      is more than 20 times higher than that in the general population. Several
      different mechanisms probably exist, and most research has focused on seizure
      related respiratory depression, cardiac arrhythmia, cerebral depression, and
      autonomic dysfunction. Data from a pooled analysis of risk factors indicate that
      the higher the frequency of tonic-clonic seizures, the higher the risk of SUDEP;
      furthermore, risk of SUDEP is also elevated in male patients, patients with long
      duration epilepsy, and those on antiepileptic polytherapy. SUDEP usually occurs
      when the seizures are not witnessed and often at night. In this Seminar, we
      provide advice to clinicians on ways to minimise the risk of SUDEP, information
      to pass on to patients, and medicolegal aspects of these deaths.

PMID- 21737138
TI  - Clinical management of gastrointestinal disturbances in patients with
      myelodysplastic syndromes receiving iron chelation treatment with deferasirox.
AB  - Myelodysplastic syndromes are characterized by ineffective hematopoiesis
      resulting in peripheral cytopenias. The majority of patients is dependent on
      regular transfusions of packed red blood cells leading to a secondary iron
      overload which might result in organ damage. Therefore, sufficient iron chelation
      therapy in selected patients is mandatory. Deferasirox (DFX) is an orally
      administered iron chelator which has been highly efficient in the treatment of
      secondary iron overload. Most frequent side effects of DFX are gastrointestinal
      disturbances, which leads in some patients to low adherence to the therapy. An
      expert panel met in Lisbon in July 2010 to develop recommendations on prevention
      and management of GI disturbances based on existing data and personal
      experiences.

PMID- 21737139
TI  - Domain requirements for the diverse immune regulatory functions of foxp3.
AB  - Foxp3 is responsible for the major immunological features of Treg cells,
      including hypoproliferation in vitro, immune suppression of conventional T cells
      and resistance to Th2 cell differentiation. In addition to the Forkhead domain,
      the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper
      domains. To understand how these domains contribute to Foxp3 functions, we
      systematically compared the roles of these domains in determining the 3 major
      immunological features of Treg cells. We designed a bridge-mediated mutagenesis
      method to generate Foxp3 mutants with complete deletion of each of the domains.
      CD4 T cells expressing the Foxp3 mutant with deletion of the N-terminal, leucine
      zipper or the forkhead domain showed robust TCR dependent proliferation in vitro,
      differentiated into Th2 cells, and lost immune suppressive activities in vitro
      and in vivo, demonstrating a complete loss of all 3 functions of Foxp3. In
      contrast, deletion of the zinc finger domain only partially impaired these
      functions of Foxp3. This result suggests that mutations in the zinc finger domain
      could lead to nonlethal autoimmune and allergic diseases, in which reduction
      rather than complete loss of Foxp3 functions is expected. In any case, deletion
      of a particular domain showed similar effects on all 3 functions of Foxp3.
      Therefore defining each of the immunological features of Treg cells requires
      intact Foxp3 proteins.

PMID- 21737140
TI  - Clearance of Propionibacterium acnes by kupffer cells is regulated by osteopontin
      through modulating the expression of p47phox.
AB  - Osteopontin (OPN) is a cytokine with multiple functions, including the regulation
      of innate immune response. However, the detailed function and mechanism of OPN in
      host defense against invaded microorganisms remain unclear. In this report, we
      revealed that OPN could affect the clearance of Propionibacterium acnes in
      kupffer cells. In a murine model of P. acnes induced hepatic granuloma, OPN
      deficient mice or wild-type (WT) mice treated with anti-OPN mAb exhibited more
      hepatic granuloma formation than WT mice. Increased infiltration of intrahepatic
      leukocytes, higher expression of TLRs, and significantly upregulated level of
      proinflammatory cytokines of liver tissue were observed in OPN-deficient mice
      after P. acnes challenge. Moreover, in vitro assay showed that kupffer cells
      isolated from OPN(-/-) mice exhibited impairment in clearance of P. acnes.
      Kupffer cells isolated from OPN(-/-) mice showed reduced level of NADPH oxidase
      mediated reactive oxygen species (ROS) in response to P. acnes, which was
      regulated by NADPH oxidase subunit p47phox. Further investigation revealed that
      OPN interaction with alphavbeta3 integrin activated PI3K and ERK signal pathways,
      leading to the expression of p47phox. Taken together, these data demonstrated an
      important role of OPN in enhancing the antimicrobial innate immune response by
      modulation of bacterium clearance activity in kupffer cells.

PMID- 21737141
TI  - Annual cost of managing bipolar disorder to the UK healthcare system.
AB  - INTRODUCTION: Bipolar disorder is a common illness characterized by recurrent
      episodes of pathological disturbances of mood. The aim of this study was to
      estimate the annual cost associated with bipolar disorder to the UK healthcare
      system (National Health Service). METHODS: A retrospective observational study
      was conducted. Primary care resource use was estimated using the IMS Disease
      Analyzer, a nationally representative sample of general practitioner (GP)
      practices. Two sources of data from the NHS Information Centre were used to
      assess resource use in secondary care and in outpatient and community mental
      health. The number of bed days and day attendances for patients hospitalized was
      obtained from the Hospital Episode Statistics (HES). This was supplemented with
      Mental Health Minimum Dataset (MHMDS) to quantify outpatient and community mental
      health face-to-face contacts. Resource use was examined between 01 April 2007 and
      31 March 2008. RESULTS: The annual NHS cost of bipolar disorder was estimated to
      be L 342 million at 2009/2010 prices. Hospitalizations accounted for 60%,
      outpatient and community mental health 26.7%, and medication in primary care 7.4%
      of the overall direct costs of care. LIMITATIONS: This study may be confounded by
      the absence of a control group. This study was limited to an assessment of direct
      healthcare costs only, not the wider societal cost of bipolar disorder.
      CONCLUSIONS: The direct medical cost of managing bipolar disorder in the UK
      healthcare system is considerable. Therapeutic strategies that optimize community
      based management, prevention of recurrence and hospitalization could reduce the
      economic burden of this illness.

PMID- 21737142
TI  - Prospective cohort study of suicide attempters aged 70 and above: one-year
      outcomes.
AB  - BACKGROUND: Most elderly persons who attempt suicide suffer from depression. This
      study aimed to investigate one-year outcomes in suicide attempters aged 70+, and
      to identify predictors of these outcomes. METHODS: 101 persons (mean age 80) who
      were hospitalized after a suicide attempt were interviewed at baseline and
      followed for one year by record linkage. Face-to-face interviews were carried out
      with 71% of those who were alive after one year (60 out of 85). Outcome measures
      included major/minor depression, Montgomery-Asberg Depression Rating Scale
      (MADRS) score, repeat non-fatal/fatal suicidal behavior and all-cause mortality.
      RESULTS: One half (52%) of all those who were interviewed scored <10 on the MADRS
      at follow-up. Among those with major depression at baseline, two thirds (26 out
      of 39) no longer fulfilled criteria for this disorder. Factors associated with
      non-remission of major depression (MADRS >= 10) included higher baseline
      depression and anxiety scores, higher suicide intent and lower Sense of
      Coherence. There were two suicides and six non-fatal repeat attempts. The
      relative risk of death (any cause) was 2.53 (95% CI = 1.45-4.10, p<0.001).
      LIMITATIONS: This is a naturalistic study; participants received non-uniform
      treatment as usual. The proportion with repeat suicidal behavior was lower than
      anticipated and the study was thus underpowered with regard to this outcome.
      CONCLUSIONS: Half of the surviving attempters were free from depressive symptoms
      at one-year follow-up and there were relatively few repeat attempts. However, all
      cause mortality remained high in this elderly cohort.

PMID- 21737143
TI  - The impact of brief depressive episodes on the outcome of bipolar disorder and
      major depressive disorder: a 1-year prospective study.
AB  - BACKGROUND: Brief depressive episodes (BDEs) cause psychosocial impairment and
      increased risk of suicide, worsening the outcome and long-term course of
      affective disorders. The aim of this naturalistic observational study was to
      assess the frequency of BDEs and very brief depressive episodes (VBDEs) and their
      impact on clinical outcome in a sample of patients with major depressive disorder
      (MDD) and bipolar disorder (BD). METHOD: Seventy patients with a diagnosis of MDD
      or BD were followed up and monthly visited for a period of 12 months, assessing
      the eventual occurrence of BDEs and/or VBDEs. Clinical and demographic variables
      of the total sample and of the groups divided according to the presence of BDEs
      or VBDEs were collected and compared by one-way ANOVAs. Hamilton Depression
      Rating Scale 21 items (HDRS), Young Mania Rating Scale (YMRS), Clinical Global
      Impression (severity of illness) (CGIs) and the Short Form Health Survey (SF-36
      item 1) were administered at baseline and logistic regression was performed to
      evaluate whether baseline scores were predictive of the onset of BDEs or VBDEs.
      RESULTS: BDEs (88.6% of the total sample), VBDEs (44.3% of the total sample) and
      BDEs+VBDEs (40.0% of the total sample) were found to occur frequently across the
      sample. BDE patients showed more death thoughts during major depressive episodes
      (chi(2) = 4.14, df = 1, p = 0.04, Phi = 0.24) compared to patients without BDEs.
      Indeed VBDE patients showed a higher rate of hospitalization (chi(2) = 5.71, df =
      1, p = 0.031, phi = 0.29), a more frequent prescription of a combined treatment
      (chi(2) = 13.07, df = 7, p = 0.03, phi = 0.43) and higher scores at SF-36 item 1
      (F = 6.65, p = 0.01) compared to patients without VBDEs. Finally, higher SF-36
      item 1 scores were found to be predictive of VBDEs (odds ratio = 2.81, p = 0.03).
      DISCUSSION: Major depressives, either unipolar or bipolar, with BDEs or VBDEs
      showed a worse outcome, represented by a more severe psychopathology and higher
      rates of hospitalization. VBDEs were predicted by a negative subjective general
      health perception. Studies with larger samples and longer follow-up are warranted
      to confirm the results of the present study.

PMID- 21737144
TI  - Association study of DRD3 gene in schizophrenia in Mexican sib-pairs.
AB  - Schizophrenia is a heritable, complex mental disorder. We analysed the DRD3 gene
      as a candidate to be related to schizophrenia and clinical features in affected
      sib-pairs. A positive association with the -250A/Ser9 haplotype and a trend
      toward an association with formal thought disorder were observed. A synergic
      effect of DRD3 polymorphisms on schizophrenia susceptibility is suggested.

PMID- 21737145
TI  - Further development of a scale of perceived expressed emotion and its evaluation
      in a sample of patients with eating disorders.
AB  - High expressed emotion (EE) as measured by the Camberwell Family Interview (CFI)
      predicts the course of eating disorders (ED). Despite its important contribution
      to the field, the CFI has two major limitations; it is time-consuming and it does
      not consider the patient's perspective. Obtaining the patient's view may help
      shed light on the dyadic nature of caregiver's EE and the patient's illness
      course. The objectives of our study of 77 patients with ED were to develop
      further a brief measure to assess the patients' perceptions of their caregivers'
      EE, the patient version of the Brief Dyadic Scale of Expressed Emotion (BDSEE),
      and to evaluate its psychometric properties. Three clearly separate factors were
      identified: perceived criticism, perceived emotional overinvolvement, and
      perceived warmth. The BDSEE also demonstrated good levels of reliability and
      construct validity. The BDSEE subscales are significantly related to other
      measures of the perceived family emotional climate and to the CFI, the gold
      standard in the field of EE. The clinical implications of the ED patients'
      perceptions of their caregivers' EE are discussed. Findings support the utility
      of the expanded BDSEE for both research and clinical practise in assessing the
      perspective of patients with ED.

PMID- 21737146
TI  - Human T-cell responses to botulinum neurotoxin: proliferative responses in vitro
      of lymphocytes from botulinum neurotoxin A-treated movement disorder patients.
AB  - We determined the T-cell responses against botulinum neurotoxin type A (BoNT/A)
      and tetanus toxin (TeNT) of peripheral blood lymphocytes from 95 BoNT-treated
      patients and 63 non-treated control subjects. The patient group included 80
      cervical dystonia and 15 other movement disorder cases. Positive T-cell responses
      to BoNT/A were detected in 70% of the treated patients, and in only 3% of
      controls. T-cell responses of BoNT-treated patients against BoNT/A did not differ
      between patients who were clinically responsive and those who had become non
      responsive to the treatment. BoNT-treated patients gave significantly higher in
      vitro T-cell responses to TeNT than did the controls.

PMID- 21737147
TI  - Myeloid lineage cells inhibit neurite outgrowth through a myosin II-dependent
      mechanism.
AB  - The molecular mechanisms that underlie the axonal damage that accompanies CNS
      inflammation are largely unknown. Here, we investigate the effects of immune
      cells on neuronal viability and axonal growth and show that conditioned media
      from myeloid lineage cells inhibit neurite outgrowth without causing apoptosis.
      Treatment with monocyte conditioned medium enhances myosin light chain
      phosphorylation in neurons and the neurite outgrowth inhibitory effect of myeloid
      lineage cells can be attenuated with the myosin II inhibitor blebbistatin. Our
      results suggest that in the context of CNS inflammation myeloid cells may limit
      axonal repair in the CNS via a myosin II-dependent mechanism.

PMID- 21737148
TI  - Parenchymal accumulation of CD163+ macrophages/microglia in multiple sclerosis
      brains.
AB  - Reactive macrophages/microglia exert both protective or damaging effects in
      multiple sclerosis (MS), which contribute to the relapsing-remitting nature of
      MS. CD163 is considered a marker of M2 (alternatively activated) macrophages. In
      the MS brain, CD163(+) perivascular macrophages express molecules for antigen
      recognition and presentation. Here we further investigated the accumulation of
      CD163(+) macrophages/microglia in the parenchyma of MS brains. CD163 expression
      pattern was investigated in different lesions of brain tissue specimens from five
      MS brains and five neuropathologically unaffected controls by
      immunohistochemistry. In the parenchyma of normal brain samples, immunoreactivity
      (IR) of CD163 was absent. In acute active lesions and at the rim of chronic
      active lesions of MS, strong accumulation of CD163(+) macrophages/microglia was
      seen. In chronic inactive lesions and in the center of chronic active lesion,
      CD163(+) macrophages/microglia were rare. Further, double-labeling showed that
      parenchymal and perivascular CD163(+) macrophages/microglia were myelin basic
      protein positive and HLA-DR(+), suggesting that CD163(+) macrophages/microglia
      could ingest and present antigen. In addition, in vitro incubating macrophage
      RAW264.7 cells with myelin turned LPS-induced inflammatory macrophages into an
      anti-inflammatory phenotype, indicating that myelin basic protein positive,
      CD163(+) macrophages/microglia in MS might have anti-inflammatory effects. The
      parenchymal CD163(+) macrophages/microglia, which had the capacity for antigen
      ingestion and presentation, might contribute to the resolution of inflammation in
      MS.

PMID- 21737149
TI  - Intraoperative electrically evoked stapedius reflex thresholds in children
      undergone cochlear implantation: round window and cochleostomy approaches.
AB  - OBJECTIVES: To study the best electrically stimulation in cochlear implant
      surgery with round window (RW) and Promontory cochleostomy approaches with
      electrically evoked stapedius reflex thresholds (ESRT) intraoperatively. METHODS:
      Thirty-nine children underwent CI surgery were included for this study. The
      surgical procedures consisted of RW and Promontory cochleostomy. ESRT for each
      1st, 3rd, 6th and 12th electrodes (E) were determined. Statistical evaluation was
      done for the comparison of the thresholds and duration times for both groups.
      RESULTS: The duration times of ESRT for E1, E3, E6 and E12 electrodes was shorter
      in RW group compared with the Promontory group (p<0.05). The statistical
      evaluation of ESRT measurements of E1, E3, E6 found p<0.001 and E12 electrode
      p<0.05 in RW group. ESRT measurements were recorded at lower threshold in the RW
      group compared with the Promontory group. CONCLUSION: The duration of
      electrically stimulation thresholds were shorter in RW group. ESRT measurements
      were recorded at lower threshold in the RW group compared with the Promontory
      group. RW insertion offers best electrically stimulation relative to electrode
      insertion via a promontory cochleostomy.

PMID- 21737150
TI  - Lingual tonsils hypertrophy; a cause of obstructive sleep apnea in children after
      adenotonsillectomy: operative problems and management.
AB  - OBJECTIVE: Although adenotonsillar hypertrophy has been reported to be the
      commonest cause of pediatric obstructive sleep apnea (OSA), enlargement of the
      lingual tonsils is increasingly being recognized as a cause, even after
      adenotonsillectomy. The aim of our study was to elucidate the lingual tonsils
      hypertrophy as a cause of pediatric OSA and also to evaluate the efficacy of
      lingual tonsillectomy in relieving symptoms of the disease considering the peri
      operative problems and management. METHODS: Sixteen children with lingual tonsils
      hypertrophy after adenotonsillectomy were included in the study. Computerized
      tomography (CT) and/or magnetic resonance imaging (MRI) were used for detection
      of the lesions. They underwent lingual tonsillectomy with special anesthetic
      care, flexible laryngoscopy and polysomnography were done pre- and post
      operatively. Follow up of the patients was carried out for at least 1 year.
      RESULTS: Three cases developed post-operative airway obstruction that is caused
      by tongue base edema. Complete improvement of snoring and apnea was achieved in
      10 cases. Despite complete ablation of lingual tonsils, persistent snoring was
      detected in six cases, while apnea was detected in two cases. Down's syndrome,
      mucopolysaccharidoses, and obesity may be underlying factors for persistent
      symptoms. CONCLUSIONS: Lingual tonsils hypertrophy could be the cause of
      obstructive sleep apnea in children after adenotonsillectomy, lingual
      tonsillectomy is an effective treatment for these cases, however peri-operative
      airway problems should be expected and can be managed safely. Persistent symptoms
      after lingual tonsillectomy may be due to the presence of co-morbidities such as
      cranio-facial deformities, obesity, and/or mucopolysaccharidoses.

PMID- 21737151
TI  - Positive association of pro-inflammatory biomarkers and increased oxidative
      stress in the healthy elderly.
AB  - To investigate the relationship between oxidative stress and pro-inflammatory
      status in healthy elderly people. A total of 1205 healthy elderly Chinese people
      (age: 65-83 years old; 861 males, 344 females) who visited the Geriatric
      Department for a thorough physical examination between May 20 and July 23, 2008
      were screened and 118 of them were recruited for further evaluation of oxidative
      stress (total antioxidation capacity, superoxide dismutase (SOD) activity,
      xanthine oxidase (XO) activity and serum hydrogen peroxide (H(2)O(2)) level) and
      pro-inflammatory status (serum C-reactive protein (CRP) and interleukin-6 (IL-6)
      level). The total anti-oxidation capacity and SOD activity were decreased while
      the serum H(2)O(2) level and XO activity were elevated in groups with higher CRP
      or IL-6 level. Linear stepwise regression showed that body mass index (BMI),
      total antioxidation capacity, SOD activity, H(2)O(2) level and XO activity were
      predictors for CRP level, while age, BMI, H(2)O(2) level and XO activity were
      predictors for IL-6 level. Pro-inflammatory status is associated with increased
      oxidative stress in healthy elderly population.

PMID- 21737152
TI  - Nutritional status and epidemiological profile of elderly people.
AB  - We intended to identify and evaluate the association between the socio
      demographic and epidemiological characteristics of elderly people with their
      nutritional characteristics. This is a transversal study PMTI (from the
      Portuguese name of "Programa Municipal da Terceira Idade"), conducted at Vicosa,
      MG, Brazil. We analyzed 93 records of elderly people registered since 2006 and
      who underwent nutritional care. After having analyzed the questionnaire, we
      performed the descriptive and association analyses in the Epi Info (version 6.04)
      and Minitab softwares. Of the 93 analyzed records, most elderly people were women
      (80.4%), with an average of 72 years of age, of which 13.0% were long-lived
      people. The mean body mass index (BMI) was 27.4 kg/m(2), and 50.5% were
      overweight. We have found 26.8% elderly patients with hypertension, and 31.6%
      took antihypertensives. Elderly patients who were overweight are 4.54 times more
      likely to have arterial hypertension (odds ratio (OR)=4.54; 95% confidence
      interval (CI)=1.2-2.45). Only 7.5% smoked, 30.1% were alcoholics and 60.2% made
      physical activities. Inadequacies were found regarding the servings of fruits,
      dairy products, vegetables and sugars consumed. However, the servings of cereals,
      leguminous, meat and fat consumed were appropriate. This study showed that the
      nutritional diagnosis and the epidemiological and socio-demographic studies are
      critical tools to understand this population group, in addition to being
      important to the planning of health actions.

PMID- 21737153
TI  - The metabolic syndrome, smoking, inflammatory markers and obesity.

PMID- 21737154
TI  - Cardiovascular manifestations of mucopolysaccharidosis type VI (Maroteaux-Lamy
      syndrome).
AB  - The aim of the article is to gather and summarize the published data about the
      incidence, course of illness, treatment possibilities and complications of
      cardiovascular disorders in patients with mucopolysaccharidosis type VI (MPS VI)
      also known as Maroteaux-Lamy syndrome. MPS VI is a lysosomal storage disorder
      caused by deficient activity of N-acetylogalactosamine-4-sulfatase leading to
      progressive intracellular accumulation of glycosaminoglycans. The relatively low
      birth prevalence ranging from 1 in 43,000 to 1 in 1.5 million births mirrors the
      limited descriptions of the cardiovascular disorders in the medical literature.
      Patients with MPS VI can be specifically treated with enzyme replacement therapy.
      Extra-cardiac features include growth retardation, coarse facial features, stiff
      joints, skeletal malformations (dysostosis multiplex), respiratory problems,
      corneal clouding, and hepatosplenomegaly. The clinical presentation varies
      considerably, however the development of heart disease and cardiac dysfunction is
      a serious problem in the majority of patients. The most characteristic cardiac
      presentation is valvular disease, while other MPS VI patients also develop
      cardiomyopathy, fibroelastosis, pulmonary hypertension, cardiac conduction system
      disorders and other complications. There are also reports on acute heart failure.
      Early cardiovascular manifestation may escape detection since joint stiffness or
      skeletal malformations limit maximal exercise levels and respiratory system
      involvement may mask the underlining cardiac insufficiency. A correct and timely
      diagnosis offers the possibility of disease-specific treatment leading to
      sustained clinical benefits for cardiac and non-cardiac MPS VI manifestations.

PMID- 21737155
TI  - Platelet expression of stromal-cell-derived factor-1 (SDF-1): an indicator for
      ACS?
AB  - BACKGROUND: Acute coronary syndrome (ACS) along with myocardial ischemic injury
      are the leading causes for chest pain. Platelet surface expression of stromal
      cell-derived factor-1 (SDF-1) is enhanced during ischemic events and may play an
      important role in trafficking hematopoietic progenitor cells for tissue
      regeneration and neovascularization. This study examined the platelet surface
      expression of SDF-1 in patients with chest pain. METHODS: We consecutively
      evaluated 1000 patients, who were admitted to the emergency department with chest
      pain. Platelet surface expression of GPIb and SDF-1 was determined by two-color
      whole blood flow cytometry. RESULTS: Patients with ACS showed significantly
      enhanced SDF-1 expression on admission compared to patients with other causes
      such as stable angina pectoris (SAP) and other origin of chest pain (CPO) (ACS
      vs. SAP/CPO (mean fluorescence intensity (MFI)+/- SD): 39.7 +/- 26.3 vs. SAP:
      37.6 +/- 31.5;P=0.045; arterial hypertension: 27.3 +/- 12.7;P=0.003; orthopedic
      disease: 22.1 +/- 6.5;P=0.014; pulmonary embolism: 26.6 +/- 19.1;P=0.003; Da
      Costa's syndrome: 22.1 +/- 12.5;P=0.021; inflammatory cardiomyopathy: 19.8 +/-
      11.5;P=0.025). Logistic regression analysis showed that surface expression of
      platelet SDF-1 was significantly associated with ACS (P=0.026), however, the
      superiority of troponin-I in predicting ACS remains on a high level (P=0.001).
      Areas under the curve of receiver operating characteristic analysis revealed
      0.718 (95% confidence interval (CI):0.680-0.757) using SDF-1, and 0.795
      (95%CI:0.760-0.829) applying troponin-I baseline serum levels. Patients with
      enhanced SDF-1 levels (cutoff:MFI >= 27.7) had a 1.4-fold relative risk
      (95%CI:1.17-1.52) for ACS. CONCLUSIONS: Platelet SDF-1 surface expression was
      significantly enhanced in patients with ACS compared to SAP or CPO. Determination
      of platelet SDF-1 may be useful as an early additional biomarker for
      cardiovascular risk stratification.

PMID- 21737156
TI  - Subclinical atherosclerosis in menopausal women with low to medium calculated
      cardiovascular risk.
AB  - BACKGROUND: The menopausal status is closely related with cardiovascular disease
      (CVD). Nevertheless, it is still not included in risk stratification by total
      cardiovascular risk estimation systems. The present study aimed to evaluate the
      extent of subclinical vascular disorders in young healthy postmenopausal women.
      METHODS: This cross-sectional study consecutively recruited 120 healthy
      postmenopausal women without clinically overt CVD or diabetes, aged 41-60 years
      and classified as not high-risk by the Heartscore (<5%). In addition to risk
      factors used for Heartscore calculations, years since menopause and associated
      risk factors (triglycerides (range 37-278 mg/dl), waist circumference (62-114
      cm), fasting blood glucose (69-114 mg/dl) and HOMA-IR (0.44-5)) were also
      assessed. Carotid-femoral pulse wave velocity, carotid and femoral intima-media
      thickness in the abnormal range as well as atheromatous plaques both in carotid
      and femoral arteries were used to define the presence of subclinical
      atherosclerosis. RESULTS: Subclinical atherosclerosis and the presence of at
      least one plaque were identified in 55% and 28% of women, respectively. Subjects
      with subclinical atherosclerosis had higher age, years since menopause, HOMA-IR
      and blood pressure. By multivariate analysis years since menopause and systolic
      blood pressure independently determined subclinical atherosclerosis while 79% of
      intermediate-risk women (Heartscore 2-4.9%) being in menopause for at least 4
      years would be reclassified to a higher risk for the presence of atherosclerosis.
      CONCLUSION: Subclinical atherosclerosis was highly prevalent in postmenopausal
      women with low to medium Heartscore. Thus our data suggest that menopausal status
      and associated risk factors should be additionally weighted in risk calculations,
      regarding primary prevention strategies in this population.

PMID- 21737157
TI  - Telomere/telomerase system impairment in circulating angiogenic cells of
      geriatric patients with heart failure.
AB  - BACKGROUND: The functional characteristics of circulating angiogenic cells (CACs)
      are impaired in congestive heart failure (CHF) patients, suggesting that CAC
      dysfunction could contribute to CHF pathogenesis. However, the underlying
      mechanisms are only partly unraveled. No data are currently available regarding
      telomere/telomerase system in CACs of CHF patients. METHODS: CACs were obtained
      from 80 subjects: 40 healthy control subjects (CTR) [median age (IQR), 80 (76-85
      yrs)] and 40 patients affected by post-ischemic cardiomyopathy CHF [median age
      (IQR), 82 (77-89)]. CAC and leukocyte telomere length, assessed as T/S ratio, and
      telomerase (TERT) activity were determined in all the enrolled subjects.
      Specificity and sensitivity of CAC and leukocyte T/S in discriminating between
      CHF and CTR were evaluated using Receiver Operator Characteristic (ROC) curve
      analysis and reported as AUC values. CD34+/VEGFR2+ number and pro-inflammatory
      cytokines plasma levels, such as IL-6 and TNF-alpha, were also measured. RESULTS:
      CAC T/S and TERT activity were significantly reduced in CHF patients compared to
      CTR subjects. In leukocytes, only a significant T/S reduction was observed. AUC
      values were higher for CAC T/S with respect to leukocyte T/S (AUC=0.89, and
      AUC=0.73, P<0.01, respectively). In multivariate analysis, leukocyte T/S, CAC
      T/S, CAC TERT activity and NT-proBNP levels were confirmed as parameters
      significantly associated with CHF. CD34+/VEGFR2+ number, IL-6 and TNF-alpha
      plasma levels were significantly increased in CHF patients. CONCLUSIONS: CACs
      from CHF patients are characterized by telomere/telomerase system impairment,
      providing new insight into the clinical relevance of CACs in CHF pathogenesis.

PMID- 21737158
TI  - Impact of diastolic dysfunction on the outcome of catheter ablation in patients
      with atrial fibrillation.
AB  - OBJECTIVE: To evaluate the impact of diastolic dysfunction on the outcome of
      atrial fibrillation (AF) ablation. METHODS: Eighty consecutive patients with drug
      refractory symptomatic AF who underwent AF ablation were enrolled (65 males, 58
      +/- 10 years, 65 paroxysmal AF, 15 persistent AF). All patients underwent
      extensive pulmonary vein isolation with a double lasso technique using CARTO
      MERGE. Diastolic dysfunction was defined as a ratio of the mitral inflow early
      filling velocity to the velocity of the early medial mitral annular ascent of
      >10. The clinical and echocardiographic data were compared between the patients
      with and without diastolic dysfunction, and between the patients with and without
      AF recurrences after the AF ablation. RESULTS: Twenty-nine out of all the
      patients (36.3%) had diastolic dysfunction. Compared with the patients without
      diastolic dysfunction, the patients with diastolic dysfunction had higher brain
      natriuretic peptide (p=0.001) and C-reactive protein (p=0.023) levels, and a
      larger left atrial diameter (P=0.019). The AF-free rate after a single or repeat
      AF ablation procedure in the patients with diastolic dysfunction was lower than
      that in those without diastolic dysfunction (p=0.005 and p=0.013 by the log-rank
      test, respectively). In the univariate analysis, the patients with persistent AF
      and diastolic dysfunction were likely to have AF recurrences after a single AF
      ablation. The multivariate analysis indicated diastolic dysfunction as the only
      independent predictor of an AF recurrence after a single AF ablation (P=0.023).
      CONCLUSION: The patients with diastolic dysfunction had a worse outcome of the AF
      ablation not only for a single procedure but also a repeat procedure.

PMID- 21737160
TI  - 3-dimensional optical frequency domain imaging for the evaluation of primary
      percutaneous coronary intervention in ST-segment elevation myocardial infarction.

PMID- 21737161
TI  - Redefinition of myocardial infarction: impact on incidence, management and
      prognosis in Quebec subpopulation.

PMID- 21737162
TI  - Wine consumption and risk of cardiovascular events after myocardial infarction:
      results from the GISSI-Prevenzione trial.
AB  - BACKGROUND: To evaluate the association of wine intake with incident
      cardiovascular events (CVE) and total mortality after myocardial infarction (MI).
      METHODS: We used prospectively ascertained information among 11,248 Italian
      patients with recent MI enrolled in the GISSI-Prevenzione Trial. Usual wine
      consumption has been categorised as never/almost never, up to 0.5L/day, and
      >0.5L/day. Multiple imputation was used for missing values at baseline and during
      follow-up. We assessed adjudicated cumulative incidence of major CVE during
      3.5years of follow-up and total mortality at long-term follow-up (7.3years),
      respectively. Multivariate Cox proportional hazards models were fitted to
      estimate hazard ratios (HR) first using data at baseline and then updated using
      time-varying covariates. RESULTS: During 37,021 person-years of follow-up, 1168
      CVE occurred. Moderate wine intake at baseline was associated with significantly
      reduced risk of CVE (adjusted HR 0.87; 95% CI 0.76-0.99) as compared with non
      drinkers. In time-updated analyses, results were virtually the same, though they
      were barely statistically not significant (adjusted HR 0.88; 95% CI 0.77-1.00).
      Wine intake was associated with lower risk of total mortality. In time-updated
      adjusted analyses, patients with wine consumption up to 0.5L/day (HR 0.83; 95% CI
      0.74-0.92) and >0.5L/day (HR 0.77; 95% CI 0.63-0.94) had lower mortality compared
      with non-drinkers (P for trend=0.0003). CONCLUSIONS: Among patients with
      established heart disease, moderate consumption of wine seems to be associated
      with lower incidence of CVE and total mortality as compared with non drinkers.

PMID- 21737163
TI  - Range of right heart measurements in top-level athletes: the training impact.
AB  - OBJECTIVES: To explore the full range of right heart dimensions and the impact of
      long-term intensive training in athletes. BACKGROUND: Although echocardiography
      has been widely used to distinguish the athlete's heart from pathologic left
      ventricular (LV) hypertrophy, only few reports have described right ventricular
      (RV) and right atrial (RA) adaptations to extensive physical exercise. METHODS:
      650 top-level athletes [395 endurance- (ATE) and 255 strength-trained (ATS); 410
      males (63.1%); mean age 28.4 +/- 10.1; 18-40 years] and 230 healthy age- and sex
      comparable controls underwent a transthoracic echocardiographic exam. Along with
      left heart parameters, right heart measurements included: RV end-diastolic
      diameters at the basal and mid-cavity level; RV base-to-apex length; RV proximal
      and distal outflow tract diameters; RA long and short diameters; and RA area.
      Tricuspid annular plane systolic excursion and RV tissue Doppler systolic peak
      velocity were assessed as indexes of RV systolic function. Pulmonary artery
      systolic pressure (PASP) was estimated from the peak tricuspid regurgitant
      velocity. RESULTS: ATS showed increased sum of wall thickness and relative wall
      thickness, whereas left atrial volume, LV end-diastolic volume, LV stroke volume
      and PASP were significantly higher in ATE. RV and RA measurements were all
      significantly greater in ATE than in ATS and controls. ATE also showed improved
      early diastolic RV function, whereas RV systolic indexes were comparable among
      groups. On multivariate analysis, type and duration of training (p<0.01), PASP
      (p<0.01) and LV stroke volume (p<0.001) were the only independent predictors of
      the main RV and RA dimensions in athletes. CONCLUSIONS: This study delineates the
      upper limits of RV and RA dimensions in highly-trained athletes. Right heart
      measurements were all significantly greater in elite endurance-trained athletes
      than in age- and sex-matched strength athletes and controls. This should be
      considered as a "physiologic phenomenon" when evaluating athletes for sports
      eligibility.

PMID- 21737164
TI  - Predictors of late recurrence of atrial fibrillation after catheter ablation.
AB  - BACKGROUND: To predict the recurrence of atrial fibrillation is important for
      selecting patients who will be undergoing catheter ablation, several studies
      respectively evaluated the risk factor of the recurrence of atrial fibrillation
      post-ablation. OBJECTIVE: To investigate the factors predicting the recurrence of
      atrial fibrillation (AF) after catheter ablation. METHODS: 186 patients (55.12 +/
      12.06 years, 123 male) including 161 paroxysmal AF and 25 non-paroxysmal AF who
      underwent catheter ablation were studied. Clinical datum before and during
      ablation were recorded, and systematic follow-up was conducted after ablation.
      Univariate and multivariate analyses were carried out to determine the factors
      predicting late recurrence of AF (LRAF) which means AF recurrence after 3 months.
      RESULTS: There were 47(25.27%) patients who experienced LRAF. Multivariate
      Logistic regression analysis was carried out to the parameters that P<0.10 in the
      univariate analysis, which includes overweight/obesity, metabolic syndrome
      (MetS), AF categories, duration of AF history, left atrial diameter (LAD),
      diabetes mellitus, ablation strategies, procedural failure and early recurrence
      of AF after ablation (ERAF). Ultimately, the results demonstrated that
      overweight/obesity (OR=4.71, 95% CI 1.71-12.98, P=0.003), MetS (OR=4.41, 95% CI
      1.56-12.46, P=0.005), procedural failure (OR=58.34, 95% CI 6.83-498.34, P<0.001),
      and ERAF (OR=3.18, 95% CI 1.07-9.44, P=0.037) were independent predictors of AF
      recurrence after ablation. CONCLUSION: Overweight/obesity, metabolic syndrome,
      procedural failure and ERAF are independent predictors of late recurrence of
      atrial fibrillation in this group of patients.

PMID- 21737165
TI  - Adjunctive balloon dilatation after stent deployment: beneficial or deleterious?
AB  - The practice of adjunctive balloon post-dilatation is not consistent among
      interventionalists, particularly in the setting of acute myocardial infarction
      (AMI). There have been some concerns about the risks of adjunctive balloon post
      dilatation, particularly in the setting of acute coronary syndrome (ACS). This
      review will examine the data on the angiographic and clinical effects, and the
      risks of adjunctive balloon post-dilatation of stents in the treatment of
      coronary artery disease.

PMID- 21737166
TI  - Factors associated with infection by Campylobacter fetus in beef herds in the
      Province of Buenos Aires, Argentina.
AB  - Campylobacter fetus is a major venereal pathogen of cattle that is considered to
      be widespread among the livestock population of Argentina. The disease accounts
      for a 10% reduction in the weaning rate of Argentine infected herds and annual
      losses of $165 million. A case-control, questionnaire-based study was developed
      with the objective of quantifying the association between C. fetus infection and
      demographic, husbandry, and sanitary factors in 196 herds located in the province
      of Buenos Aires, Argentina. Abortions observed in the herd (OR=3.08, 95% CI=1.52,
      6.23), and trespassing of bulls from neighboring herds (OR=2.03, 95% CI=0.98,
      4.20), were positively associated with the risk of finding C. fetus-infected
      bulls, whereas buying bulls was a protective factor for the disease (OR=0.53, 95%
      CI=0.26, 1.08). Results presented here will help to develop and implement actions
      aimed at preventing the spread and reducing the incidence of C. fetus infection
      in the beef cattle population of Argentina.

PMID- 21737167
TI  - Postal dosimetry audit test for small photon beams.
AB  - BACKGROUND AND PURPOSE: Small radiation beams (<4 cm width) are being
      increasingly used in the delivery of advanced techniques as Intensity Modulated
      Radiotherapy (IMRT) and Stereotactic Radiosurgery (SRS). Dose measurements in
      small beams present challenges not encountered for larger beams. A postal audit
      with Thermoluminiscent Dosimeters (TLD) was developed to check the doses in small
      photon beams. A validation test in real conditions was carried out in fourteen
      centres. MATERIAL AND METHODS: The TLD postal audit employs very small chips
      (1*1*1 mm(3)) of TLD-100 inserted at 5 and 10 cm of depth in a cylindrical PMMA
      phantom designed for this purpose. This experimental system is mailed to the
      audited centres to be irradiated with beams of 1 and 3 cm of side or diameter.
      The prescribeddose is 1.5 Gy at 10 cm. The properties of this system were studied
      experimentally and by Monte Carlo (MC) simulation, before the external test.
      RESULTS: Deviations between the prescribed and measured absorbed doses are below
      5% for 69% (1*1 cm(2) beam) and 64% (3*3 cm(2) beam) of the audited centres. When
      deviations are above 5%, their causes have been investigated and led to
      corrections. CONCLUSION: The developed postal audit is suitable to verify the
      absorbed doses in small photon beams with an accuracy of 2.9% (1 s).

PMID- 21737168
TI  - Dependence of cell survival on instantaneous dose rate of a linear accelerator.
AB  - BACKGROUND AND PURPOSE: With the development of flattening filter-free linear
      accelerators for radiotherapy, the instantaneous dose rate has increased by
      approximately a factor 4. This leads to the question of whether there may be a
      radiobiological consequence. The present study investigates the radiobiological
      effect of this high instantaneous dose rate on two cell lines. MATERIALS AND
      METHODS: A Varian Trilogy TX linear accelerator was used to directly compare the
      effect of three different dose rates (5.01, 9.99 and 29.91 Gy/min, with
      instantaneous dose rates in the pulse of 56.5, 112.8 and 338 Gy/s) on clonogenic
      survival. V79 and FaDu(DD) cells were irradiated with doses in a range from 1 to
      10 Gy in order to obtain dose response curves. RESULTS: For both cell lines,
      there is not observed any effect of the instantaneous dose rate on cell survival.

PMID- 21737169
TI  - Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter
      region after radiotherapy for prostate cancer.
AB  - BACKGROUND AND PURPOSE: Tobacco smoking can cause vascular injury, tissue hypoxia
      and fibrosis as can ionizing radiation. However, we do not know if tobacco
      smoking increases the risk of long-term side effects after radiotherapy for
      prostate cancer. METHODS: We identified 985 men treated with radiotherapy for
      prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing
      after radiotherapy for prostate cancer were assessed through a study-specific
      questionnaire as were smoking habits and demographic factors of all these men. In
      the questionnaire the prostate-cancer survivors were asked to report symptom
      occurrence the previous six months. RESULTS: We obtained information on tobacco
      smoking from 836 of the 985 prostate-cancer survivors with a median time to
      follow-up of six years (range 2-14 years). The prevalence ratio of defecation
      urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2-2.2).
      Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2-6.5), the
      sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3-3.3)
      and for sudden emptying of all stools into clothing without forewarning 4.7 (95%
      CI 2.3-9.7). CONCLUSION: Tobacco smoking among prostate-cancer survivors treated
      with radiotherapy increases the risk of certain long-lasting symptoms from the
      bowel and anal-sphincter region.

PMID- 21737170
TI  - The role of homologous recombination in radiation-induced double-strand break
      repair.
AB  - DNA double-strand breaks (DSBs) represent the most biologically significant
      lesions induced by ionizing radiation (IR). HR is the predominant pathway for
      repairing one-ended DSBs arising in S-phase when the replication fork encounters
      single-stranded breaks or base damages. Here, we discuss recent findings that two
      ended DSBs directly induced by X- or gamma-rays in late S- or G2-phase are
      repaired predominantly by NHEJ, with HR only repairing a sub-fraction of such
      DSBs. This sub-fraction represents DSBs which localize to heterochromatic DNA
      regions and, which in control cells, are repaired with slow kinetics over many
      hours post irradiation. The observation that defined DSB populations are repaired
      by either NHEJ or HR suggests an assignment of specific tasks for each of the two
      processes. Furthermore, heavy ion induced complex DSBs, which are in general more
      slowly repaired than X- or gamma-ray induced breaks, are nearly always repaired
      by HR independent of chromatin localization suggesting that the speed of repair
      is an important factor determining the DSB repair pathway usage. Finally, NHEJ
      and HR can, under certain conditions, also compensate for each other such that
      DSBs normally repaired by one pathway can undergo repair by the other if genetic
      failures necessitate the pathway switch.

PMID- 21737171
TI  - Influence of water activity and temperature on growth and mycotoxin production by
      Alternaria alternata on irradiated soya beans.
AB  - The aim of this study was to determine the effects of water activity (a(w)) (0.99
      0.90), temperature (15, 25 and 30 degrees C) and their interactions on growth and
      alternariol (AOH) and alternariol monomethyl ether (AME) production by Alternaria
      alternata on irradiated soya beans. Maximum growth rates were obtained at 0.980
      a(w) and 25 degrees C. Minimum a(w) level for growth was dependent on
      temperature. Both strains were able to grow at the lowest a(w) assayed (0.90).
      Maximum amount of AOH was produced at 0.98 a(w) but at different temperatures, 15
      and 25 degrees C, for the strains RC 21 and RC 39 respectively. Maximum AME
      production was obtained at 0.98 a(w) and 30 degrees C for both strains. The
      concentration range of both toxins varied considerably depending on a(w) and
      temperature interactions. The two metabolites were produced over the temperature
      range 15 to 30 degrees C and a(w) range 0.99 to 0.96. The limiting a(w) for
      detectable mycotoxin production is slightly greater than that for growth. Two
      dimensional profiles of a(w)* temperature were developed from these data to
      identify areas where conditions indicate a significant risk from AOH and AME
      accumulation on soya bean. Knowledge of AOH and AME production under marginal or
      sub-optimal temperature and a(w) conditions for growth can be important since
      improper storage conditions accompanied by elevated temperature and moisture
      content in the grain can favour further mycotoxin production and lead to
      reduction in grain quality. This could present a hazard if the grain is used for
      human consumption or animal feedstuff.

PMID- 21737172
TI  - Development and initial validation of the barriers to diabetes adherence measure
      for adolescents.
AB  - AIMS: The purpose of this study was to develop a measure of psychosocial barriers
      to adherence in adolescents with type 1 diabetes (T1D) and examine relationships
      to patient characteristics, adherence, and hemoglobin A1C (A1C). METHODS:
      Barriers to diabetes adherence (BDA) items were generated by researchers,
      clinicians, and patients. Adolescents aged 12-17 with T1D completed the BDA and
      an adherence measure. Hemoglobin A1C was obtained through medical chart review.
      RESULTS: Factor analysis from 123 adolescents resulted in a 21-item, five
      component solution that accounted for 64.5% of the variance. The components were
      stress and burnout, time pressure and planning, social support, parental autonomy
      support, and stigma. The BDA total and subscales were internally consistent. The
      BDA total and some components were associated with adherence and A1C. The BDA was
      the only predictor of A1C compared to demographic, clinical, and adherence
      variables (F 6.17, p<.05). Subjects with higher A1C (>8.5) showed a higher level
      of barriers (F 15.20, p<.001) and a differential profile of barriers (F 5.75,
      p<.05). CONCLUSIONS: The BDA may be useful in research and clinical settings as a
      compliment to adherence measures and to tailor educational programs. Additional
      research is necessary to establish test-retest reliability and discriminant
      validity.

PMID- 21737173
TI  - Erythrocytic enzymes and antioxidant status in people with type 2 diabetes:
      beneficial effect of Syzygium cumini leaf extract in vitro.
AB  - The aim of the present study was to investigate the effects of Syzygium cumini
      leaf extract (ASc), on Adenosine deaminase (ADA) and Acetylcholinesterase (AChE)
      activities, and also on oxidative stress parameters in erythrocytes hemolysates
      (RBCs) and erythrocytes membranes (ghosts) from type 2 diabetics patients (Type 2
      DM) under in vitro conditions. Non protein thiol groups (NP-SH), AChE, Catalase
      (CAT) and Superoxide Dismutase (SOD) activities were measure in RBCs. Further,
      ADA activity, Thiobarbituric Acid-Reactive Substances (TBARS) levels and protein
      thiol groups (P-SH) were estimated in ghosts. Also, P-SH and Vitamin C (VIT C)
      were measure in plasma sample. The results demonstrated that ADA and AChE
      activities, besides TBARS levels were higher in erythrocytes of Type 2 DM, while
      SOD activity and NP-SH levels were decreased when compared to control group. ASc,
      in vitro, reduced ADA and AChE activities and some parameters of oxidative
      stress. Furthermore, we observed correlations between VIT C and P-SH levels, ADA
      activity and P-SH levels, as well as NP-SH and TBARS levels in diabetics. The
      results suggest that ASc in vitro is able to promote the reduction of
      inflammation and oxidative stress parameters, and act against biochemical changes
      occurring in Diabetes mellitus (DM).

PMID- 21737174
TI  - ASCL1-coexpression profiling but not single gene expression profiling defines
      lung adenocarcinomas of neuroendocrine nature with poor prognosis.
AB  - BACKGROUND: Lung adenocarcinoma is heterogeneous regarding histology, etiology
      and prognosis. Although there have been several attempts to find a subgroup with
      poor prognosis, it is unclear whether or not adenocarcinoma with neuroendocrine
      (NE) nature has unfavorable prognosis. MATERIALS AND METHODS: To elucidate
      whether a subtype of adenocarcinoma with NE nature has poor prognosis, we
      performed gene expression profiling by cDNA microarray for 262 Japanese lung
      cancer and 30 normal lung samples, including 171 adenocarcinomas, 56 squamous
      cell carcinomas and 35 NE tumors. A co-expression gene set with ASCL1, an NE
      master gene, was utilized to classify tumors by non-negative matrix
      factorization, followed by validation using an ASCL1 knock-down gene set in DMS79
      cells as well as an independent cohort (n=139) derived from public microarray
      databases as a test set. RESULTS: The co-expression gene set classified the
      adenocarcinomas into alveolar cell (AL), squamoid, and NE subtypes. The NE
      subtype, which clustered together almost all the NE tumors, had significantly
      poorer prognosis than the AL subtype that clustered with normal lung samples
      (p=0.0075). The knock-down gene set also classified the 171 adenocarcinomas into
      three subtypes and this NE subtype also had the poorest prognosis. The co
      expression gene set classified the independent database-derived American cohort
      into two subtypes, with the NE subtype having poorer prognosis. None of the
      single NE gene expression was found to be linked to survival difference.
      CONCLUSION: Co-expression gene set with ASCL1, rather than single NE gene
      expression, successfully identifies an NE subtype of lung adenocarcinoma with
      poor prognosis.

PMID- 21737175
TI  - The xanthophyll cycle and antioxidative defense system are enhanced in the wheat
      hybrid subjected to high light stress.
AB  - Although the wheat hybrids have often shown higher grain yields, the
      physiological basis of the higher yields remains unknown. Previous studies
      suggest that tolerance to photoinhibition in the hybrid may be one of the
      physiological bases (Yang et al., 2006, Plant Sci 171:389-97). The objective of
      this study was to further investigate the possible mechanism responsible for
      tolerance to photoinhibition in the hybrid. Photosystem II (PSII) photochemistry,
      the xanthophyll cycle, and antioxidative defense system were compared between the
      hybrid and its parents subjected to high light stress (1500MUmolm(-2)s(-1)). The
      analyses of oxygen-evolving activity, chlorophyll fluorescence, and protein
      blotting demonstrated that the higher tolerance in the hybrid than in its parents
      was associated with its higher tolerance of PSII to photoinhibition. High light
      induced an increase in non-photochemical quenching, and this increase was greater
      in the hybrid than in its parents. There were no differences in the pool size of
      the xanthophyll cycle between the hybrid and its parents. The content of
      violaxanthin decreased significantly, whereas the content of
      zeaxanthin+antherxanthin increased considerably during high light treatments.
      However, the decrease in violaxanthin content and the increase in
      zeaxanthin+antherxanthin content were greater in the hybrid than in its parents.
      High light resulted in a significant accumulation of H(2)O(2), O(2)(-) and
      catalytic Fe, and this accumulation was less in the hybrid than in its parents.
      High light induced a significant increase in the activities of superoxide
      dismutase, catalase, ascorbate peroxidase, glutathione reductase,
      dehydroascorbate reductase, and monodehydroascorbate reductase, and these
      increases were greater in the hybrid than its parents. These results suggest that
      the higher tolerance to photoinhibition in the hybrid may be associated with its
      higher capacity for antioxidative defense metabolism and the xanthophyll cycle.

PMID- 21737176
TI  - Measuring compliance with transmission-based isolation precautions: comparison of
      paper-based and electronic data collection.
AB  - BACKGROUND: Decreasing the transmission of resistant organisms in hospitals is a
      key goal of infection prevention plans. Studies have consistently shown
      inadequate health care worker (HCW) compliance with isolation precautions.
      Evaluating adherence through direct observation of HCW behavior is considered the
      "gold standard" but is labor-intensive, requiring the collection and analysis of
      a large volume of observations. METHODS: Two methods of data collection to assess
      HCW compliance were evaluated: a manual method using a paper form (PF), with
      subsequent data entry into a database, and an electronic method using a Web-based
      form (WBF) with real-time data recording. Observations were conducted at 4
      hospitals (a total of 2,065 beds) to assess the availability of gloves, gowns,
      and masks; isolation sign postings; and HCW isolation practices. RESULTS: A total
      of 13,878 isolation rooms were observed in 2009. The median number of rooms
      observed per day was 61 for PF and 60 for WBF, and the respective mean
      observation times per room were 149 seconds and 60 seconds. Thus, use of the WBF
      provided a time savings of 89 seconds per room. CONCLUSION: Simple electronic
      forms can significantly decrease the required resources for monitoring HCW
      adherence to hospital policies. Use of the WBF decreased the observation time by
      60%, allowing for increases in the frequency and intensity of surveillance
      activities.

PMID- 21737177
TI  - Post-cataract surgery endophthalmitis outbreak caused by multidrug-resistant
      Pseudomonas aeruginosa.
AB  - In June 2010, a severe outbreak of 13 cases of post-cataract surgery
      endophthalmitis caused by multidrug-resistant Pseudomonas aeruginosa occurred.
      Pulse-field gel electrophoresis in eye isolates found 95% genetic similarity;
      however, extensive environmental and carriage investigation revealed no source of
      infection.

PMID- 21737178
TI  - Suppression of regrowth of normal skin flora under chlorhexidine gluconate
      dressings applied to chlorhexidine gluconate-prepped skin.
AB  - BACKGROUND: Catheter colonization and bloodstream infection during the first week
      after insertion of a central venous catheter have been shown to result from the
      patient's own skin flora. METHODS: The backs of 32 healthy subjects were prepped
      with a 2% chlorhexidine gluconate (CHG)/70% isopropyl alcohol antiseptic. Three
      dressings, 2 of which contained CHG, were placed on the prepped skin in a
      randomized design. Samples of aerobic bacteria were collected using the cup scrub
      method. Skin under the dressings was sampled by quadrant on days 1, 4, and 7.
      Relative suppression of regrowth was compared using an adjusted paired t test.
      RESULTS: Mean log counts were 3.2 log(10) colony-forming units (CFU)/cm(2) before
      antisepsis and 0.4 after antisepsis. Mean log counts obtained on days 1, 4, and 7
      were 0.4, 0.3, and 0.5 log(10) CFU/cm(2) for the CHG gel; 0.4, 0.4, and 0.9
      log(10) CFU/cm(2) for the CHG disk; and 0.9, 1.2, and 1.5 log(10) CFU/cm(2) for
      the Control, respectively. CONCLUSION: Skin flora was not completely eradicated
      during antisepsis, and bacterial regrowth occurred postantisepsis. The use of CHG
      dressings helped sustain a reduced bacterial count on the skin. The continuously
      releasing CHG gel maintained suppression to a greater extent than the CHG disk at
      7 days (P = .01).

PMID- 21737179
TI  - Assessing the infection prevention components of home health emergency management
      plans.
AB  - BACKGROUND: Home health emergency management plans are essential and must address
      infection prevention issues. Few home health planning documents exist, and many
      of those that have been developed do not address infection prevention issues,
      combine them with non-infection prevention issues, or are disease/event-specific.
      An all-encompassing home health infection prevention emergency management
      planning guide is needed. METHODS: A literature review and Internet search were
      conducted in the summer of 2010, and data from relevant sources were extracted. A
      spreadsheet was created delineating home health emergency management plan
      components related to infection prevention. RESULTS: Of the sources screened, 41
      were deemed relevant. Ten domains were identified: (1) having a plan; (2)
      assessing agency readiness; (3) having infection prevention policies and
      procedures; (4) having occupational health policies and procedures; (5)
      conducting surveillance and triage; (6) reporting incidents, having a
      communication plan, and managing information; (7) addressing surge capacity
      issues; (8) having anti-infective therapy and/or vaccines; (9) providing
      infection prevention education; and (10) managing water and waste management
      issues. CONCLUSION: Home health disaster planners or managers should use this
      article as an assessment tool for evaluating their agency's emergency management
      plan and for developing policies and procedures that will decrease the risk of
      infection transmission during a mass casualty event.

PMID- 21737180
TI  - [Return of the flu: leadership, teamwork and foresight].

PMID- 21737181
TI  - [Miliary tuberculosis in a patient with Crohn's disease].

PMID- 21737182
TI  - [Variability in the autonomous communities of the clinical recommendations in the
      service portfolios in primary care].
AB  - The quality guidelines established in Primary Care Service Portfolios of
      Autonomous Communities were analysed. It was observed that there were
      similarities in the number and content of the controls in children over 2 years
      old, time intervals of cardiovascular risk and breast cancer mammography
      screening. Variability was observed in the number of controls (from 2 to 8)
      recommended for infants less than 2 years old, in the time intervals of
      monitoring parameters of patients with risk factors (for example, glycosylated
      haemoglobin in the diabetic every 2, 6, or 12 months), in the time intervals in
      cervical cytology (every 3 or 5 years) and in the age periods of performing the
      cytology (from 15, 20, 25, or 30 years up to 55 or 60 years) or mammography (from
      45 or 50 years up to 60 or 65 years).

PMID- 21737183
TI  - [Offering abortion as the only option for unwanted pregnancy, a poor practice].

PMID- 21737184
TI  - Coexistence of two different types of lymphoma in a patient with Sjogren's
      syndrome. The usefulness of the PET-CT.
AB  - Sjogren syndrome is a chronic systemic autoimmune disease in which there is an
      increased risk of developing non-Hodgkin's lymphoma. Neoplastic lung involvement
      and the coexistence of different histological types of lymphoma are uncommon in
      these patients. These patients frequently have associated infectious processes,
      most of them due to oral candidiasis. When there is immunodeficiency, the
      hematogenous spread of the fungus may affect the lungs. We present the case of a
      female patient diagnosed with follicular non- Hodgkin lymphoma within the context
      of long-term Sjogren syndrome. In addition to the neoplastic nodal and splenic
      disease, the PET-CT study showed extensive lung involvement. Due to suspicion of
      a false positive result for pulmonary Candida infection, antifungal treatment was
      initiated, with no response. A further histological study showed the presence of
      a second and different type of lymphoma.

PMID- 21737185
TI  - Splenic and multiple abdominal metastases of endometrial carcinoma detected with
      FDG-PET/CT.
AB  - A 58 year old female was referred for FDG-PET/CT for restaging of endometrial
      adenocarcinoma. For evaluation of treatment, no metastases were detected on FDG
      PET/CT which was performed 18 months later after the surgery. During follow-up,
      FDG-PET/CT was performed 6 months later than the previous FDG-PET/CT for
      restaging. A lesion with increased metabolic activity (SUV max: 10.21) was
      detected at spleen which was not seen on previous FDG-PET/CT scan. The lesion was
      consistent with metastasis of endometrial carcinoma. Splenic metastasis of
      endometrial carcinoma is extremely rare. There are only 13 cases of splenic
      metastasis from endometrial carcinoma that reported in the literature before.
      There is only one splenic metastasis of endometrial carcinoma case reported in
      the literature which is imaged with FDG-PET. To best of our knowledge this is the
      first report of solitary splenic metastasis of endometrial carcinoma that is
      imaged with FDG-PET/CT.

PMID- 21737186
TI  - Prevalence of high risk genotypes of human papillomavirus in anal samples from
      men who have sex with men with abnormal cytology in Madrid.

PMID- 21737187
TI  - [Temporal trend in understanding of and attitudes to advance directives in
      patients with chronic diseases].
AB  - OBJECTIVE: To describe patients' degree of knowledge about their diseases and
      advance directives, as well as their willingness to write these documents, among
      patients with chronic diseases seen in the emergency department. METHODS: We
      performed a prospective, comparative, cross-sectional study, without intervention
      and with consecutive patient inclusion in two periods (2003 and 2008).
      Demographic and clinical data were recorded. An anonymous interview about
      patients' knowledge and opinions about their illness and their awareness of
      advance directives was performed. Previous awareness of advance directives and
      the predisposition to write these documents were taken as dependent variables,
      and factors associated with these variables were analyzed. RESULTS: In both
      periods, 381 patients with similar characteristics were included (191 in 2003 and
      190 in 2008). Patients showed greater knowledge of their disease (74% vs 55%,
      p<0,001), a greater predisposition to take part in medical decisions (62% vs 42%,
      p<0,001), and higher participation in such decisions (48% vs 35%, p=0.01) in 2008
      than in 2003. However, awareness of advance directives was slightly lower (18% vs
      23%, p=NS), and willingness to write these documents was unchanged (50% vs 50%,
      p=NS). Awareness of advance directives was associated with age less than 75 years
      and having completed secondary school. The predisposition to write advance
      directives was associated with previous awareness of these documents, considering
      oneself to be well informed, and wanting greater participation in medical
      decisions. CONCLUSIONS: Patients with chronic diseases showed greater
      understanding of their disease in the second period but awareness of advance
      directives and willingness to write these documents remained low. Information on
      these issues should be improved as an essential part of the physician-patient
      relationship.

PMID- 21737188
TI  - Service user involvement in nurse education: a report on using online discussions
      with a service user to augment his digital story.
AB  - Service user involvement is a key element within current pre- and post
      registration nurse education in the U.K. but achieving this is challenging. Most
      service user involvement is through classroom visits. Digital stories, film and
      audio are alternatives but lack the interactivity and development of reflection
      that can be achieved through face-to-face contact. This report reviews the
      background to service user involvement in healthcare professional education then
      provides a reflective account of a novel initiative whereby a spinal-injured
      patient was involved in creating a digital story around some of his in-hospital
      experiences and then engaged in online discussions with post-registration nursing
      (degree) and practice educator (masters) students. These discussions provided a
      richer experience for the students enabling them to reflect more deeply on how
      nursing care is delivered and perceived by service users. The report concludes
      that digital stories can be used with repeated groups to inspire discussion and
      reflection. Augmenting such digital stories with online discussions with the
      service user whose story is told helps practitioners develop greater empathy,
      insight and understanding which are beneficial for improving service delivery and
      nursing care.

PMID- 21737189
TI  - 'A caring professional attitude': What service users and carers seek in graduate
      nurses and the challenge for educators.
AB  - With the publication of the new NMC standards for pre-registration nursing
      education, undergraduate curricula are being written in universities across
      England. There are many drivers for the curricula but one that has until recently
      received scant attention is the service user's and carer's voice. This paper
      discusses the findings of a qualitative study that asked 52 service users and
      carers about the qualities they sought in nurses and their views on nurse
      education. Eight focus groups were conducted with a broad range of service users
      and carers from primary and secondary care, and voluntary organisations. Data
      were analysed using the framework approach facilitated by a qualitative analysis
      software programme. The sample was diverse, but there were similarities in the
      qualities they valued in nurses. They sought technical competence, knowledge and
      willingness to seek information, but overwhelmingly prioritised 'a caring
      professional attitude'. This was articulated as empathy, communication skills and
      non-judgmental patient centred care: major themes in the new NMC standards. Our
      participants also expressed concern about whether the educational preparation of
      nurses can develop these caring qualities. We discuss this concern, the
      challenges for nurse educators it presents and how we can engage service users
      and carers in shaping and delivering our new curricula.

PMID- 21737190
TI  - Can arbuscular mycorrhizal fungi improve grain yield, As uptake and tolerance of
      rice grown under aerobic conditions?
AB  - The effects of arbuscular mycorrhizal fungi (AMF) -Glomus intraradices and G.
      geosporum on arsenic (As) and phosphorus (P) uptake by lowland (Guangyinzhan) and
      upland rice (Handao 502) were investigated in soil, spiked with and without 60 mg
      As kg(-1). In As-contaminated soil, Guangyinzhan inoculated with G. intraradices
      or Handao 502 inoculated with G. geosporum enhanced As tolerance, grain P
      content, grain yield. However, Guangyinzhan inoculated with G. geosporum or
      Handao 502 inoculated with G. intraradices decreased grain P content, grain yield
      and the molar ratio of grain P/As content, and increased the As concentration and
      the ratio of grain/straw As concentration. These results show that rice/AMF
      combinations had significant (p < 0.05) effects on grain As concentration, grain
      yield and grain P uptake. The variation in the transfer and uptake of As and P
      reflected strong functional diversity in AM (arbuscular mycorrhizal) symbioses.

PMID- 21737191
TI  - Monitoring plastic ingestion by the northern fulmar Fulmarus glacialis in the
      North Sea.
AB  - The abundance of plastics in stomachs of northern fulmars from the North Sea is
      used in the OSPAR Ecological Quality Objective (EcoQO) for marine litter. The
      preliminary EcoQO defines acceptable ecological quality as the situation where no
      more than 10% of fulmars exceed a critical level of 0.1 g of plastic in the
      stomach. During 2003-2007, 95% of 1295 fulmars sampled in the North Sea had
      plastic in the stomach (on average 35 pieces weighing 0.31 g) and the critical
      level of 0.1 g of plastic was exceeded by 58% of birds, with regional variations
      ranging from 48 to 78%. Long term data for the Netherlands since the 1980s show a
      decrease of industrial, but an increase of user plastics, with shipping and
      fisheries as the main sources. The EcoQO is now also used as an indicator for
      Good Environmental Status in the European Marine Strategy Framework Directive.

PMID- 21737192
TI  - The effect of mercury on trees and their mycorrhizal fungi.
AB  - The Oak Ridge Reservation, established in 1942, was the designated site for the
      construction of the atomic bomb. During a 20-year period from 1944 to 1963
      radioactive and toxic chemical pollutants, especially mercury compounds were
      released into the surrounding waterways. Tree diversity and mycorrhizal presence
      and abundance were analyzed in the mercury-contaminated floodplains of East Fork
      Poplar Creek Oak Ridge (EFPC) (Tennessee). A subsequent greenhouse study was
      conducted to assess the phytotoxic effects of different mercuric solutions on
      Platanus occidentalis (American Sycamore), inoculated with soils from EFPC. Total
      soil mercury in the field had no effect on tree diversity. Organic species of
      mercury proved to be more toxic than inorganic species of mercury and soil
      inoculants from EFPC had no protective effects against Hg toxicity in our
      greenhouse study. Comparison of the effects of mercury contamination in our field
      and greenhouse studies was difficult due to uncontrolled factors.

PMID- 21737193
TI  - Reproductive toxicity of bisphenol A and cadmium in Potamopyrgus antipodarum and
      modulation of bisphenol A effects by different test temperature.
AB  - An OECD initiative for the development of mollusc-based toxicity tests for
      endocrine disrupters and other chemicals has recommended three test species with
      respective test designs for further standardisation. Preparing a subsequent pre
      validation study we performed a reproduction test with Potamopyrgus antipodarum,
      determining the concentration range of the selected test substances, bisphenol A
      (BPA) and cadmium (Cd). At 16  degrees C, the recommended test temperature, the
      number of embryos in the brood pouch was increased by BPA and decreased by Cd
      (NOEC: 20 MUg BPA/L and 1 MUg Cd/L). Coinstantaneous BPA tests at 7  degrees C
      and 25  degrees C demonstrated a temperature dependency of the response,
      resulting in lower NOECs (5 MUg/L respectively). As expected, reproduction in
      control groups significantly varied depending on temperature. Additional
      observations of the brood stock showed seasonal fluctuations in reproduction
      under constant laboratory conditions. The recommended temperature range and test
      conditions have to be further investigated.

PMID- 21737194
TI  - Developmental toxicity of two common corn pesticides to the endangered southern
      bell frog (Litoria raniformis).
AB  - To examine the link between corn agriculture and the observed decline of the
      endangered southern bell frog (SBF), the effects of two corn crop pesticides on
      larval growth and development were investigated. Tadpoles were exposed to
      terbufos sulfone (10 MUg/L), a major breakdown product of the insecticide
      terbufos, and the herbicide atrazine (25 MUg/L) individually and as a mixture
      until the completion of metamorphosis. Atrazine did not interact synergistically
      with terbufos sulfone or result in significant effects on growth and development
      alone, although there was some indication of accelerated metamorphosis in the
      pilot study. Terbufos sulfone alone and as a mixture (terbufos/atrazine)
      significantly slowed larval development and ultimately delayed metamorphosis. The
      observed developmental effects from an environmentally relevant concentration of
      terbufos sulfone indicates a risk posed by this persistent degradation product to
      the endangered SBF, which breeds and develops in the rice bays adjacent to corn
      fields treated with pesticides.

PMID- 21737195
TI  - Diagnostic decision making: the last refuge for general practitioners?
AB  - Nurses and pharmacists gained the right to prescribe as independent prescribers
      in the UK in 2007. Independent prescribers are responsible for the initial
      assessment of patients with diagnosed and undiagnosed conditions. Public policy
      discourse and the views expressed by health care professionals have
      conceptualised diagnostic decision making as being at a 'higher level' and more
      difficult than prescribing decision making. This paper presents five themes
      related to this premise. Firstly diagnostic decision making is put into the
      broader context of clinical reasoning which underpins all types of clinical
      decisions including both diagnostic and prescribing decisions. Secondly, the
      nature of diagnostic decision making is discussed as to whether it is indeed
      separable from the prescribing decision making process. Thirdly, the conception
      that all diagnostic decisions are inherently more difficult is contested when
      difficulty in decision making is more appropriately applied to all types of
      clinical decisions which involve greater complexity and uncertainty. The fourth
      topic concerns whether this perception of diagnoses as being more difficult is a
      response by the medical profession to the threat of independent prescribing,
      reflecting their wish to maintain professional power and dominance over other
      professions. The final section considers how expertise in diagnoses could be
      developed in nurse and pharmacist independent prescribers. To develop their
      expertise in making accurate diagnoses, medicine uses the model of learning basic
      science mechanisms followed by engagement with patient clinical problems followed
      by years of clinical experience. However this may be just one way of achieving
      diagnostic expertise. Other approaches, such as the use of deliberate practice
      and feedback, may be more suitable to the diverse range of knowledge and
      experiences of nurse and pharmacist prescribers.

PMID- 21737196
TI  - [Should we reconsider the criteria for home oxygen therapy depending on
      altitude?].

PMID- 21737197
TI  - Arterial stiffness, central hemodynamics and wave reflection in normal pregnancy
      and control nonpregnant women.
AB  - OBJECTIVES: Pregnancy is accompanied by different physiological adaptations in
      the cardiovascular system. However, information on central blood pressures, wave
      reflection, arterial stiffness in uncomplicated pregnancy compared with
      nonpregnant women is limited. STUDY DESIGN: Forty-six women (mean age 28 years)
      in the third trimester of pregnancy and 45 healthy age- and height-matched
      controls were evaluated. Arterial stiffness, central hemodynamics and wave
      reflection was assessed with the use of digital volume pulse analysis and pulse
      wave analysis. RESULTS: In comparison with nonpregnant participants, pregnant
      women had significantly lower mean (p=0.04) and central systolic (p=0.02) blood
      pressure, central pulse pressure (p=0.02), augmentation index (p=0.02) and
      augmentation pressure (p=0.002), whereas their pulse pressure amplification was
      significantly higher (p=0.001). Similarly, arterial stiffness index was higher in
      pregnant women than in healthy nonpregnant controls (p=0.006). This index was
      correlated significantly with central augmentation index and augmentation
      pressure (r=0.5, p=0.0005 and r=0.52, p=0.0002, respectively) but only in
      nonpregnant women. CONCLUSIONS: Healthy pregnancy is associated with increased
      pulse pressure amplification as well as diminished wave reflection, which results
      in lower central augmentation index and augmentation pressure. Women in the third
      trimester of pregnancy have slightly higher arterial stiffness in comparison with
      healthy nonpregnant, age- and height-matched controls. The increased value of
      measures of arterial stiffness might be secondary to a known physiological
      increase of cardiac output and the amount of circulating blood.

PMID- 21737198
TI  - Prediction of metal-adsorption behaviour in the remediation of water
      contamination using indigenous microorganisms.
AB  - In recent years, the adsorption of heavy metal cations onto bacterial surfaces
      has been studied extensively. This paper reports the findings of a study
      conducted on the heavy metal ions found in mine effluents from a mining plant
      where Co(2+) and Ni(2+) bearing minerals are processed. Heavy metal ions are
      reported to be occasionally present in these mine effluents, and the proposed
      microbial sorption technique offers an acceptable solution for the removal of
      these heavy metals. The sorption affinity of microorganisms for metal ions can be
      used to select a suitable microbial sorbent for any particular bioremediation
      process. Interactions of heavy metal ions (Co(2+) and Ni(2+)) and light metal
      ions (Mg(2+) and Ca(2+)) with indigenous microbial cells (Brevundimonas spp.,
      Bacillaceae bacteria and Pseudomonas aeruginosa) were investigated using the
      Langmuir adsorption isotherm, pseudo second-order reaction kinetics model and a
      binary-metal system. Equilibrium constants and adsorption capacities derived from
      these models allowed delineation of the effect of binding affinity and metal
      concentration ratios on the overall adsorption behaviour of microbial sorbents,
      as well as prediction of performance in bioremediation systems. Although
      microbial sorbents used in this study preferentially bind to heavy metal ions, it
      was observed that higher concentrations (>90 mg/l) of light metal ions in multi
      metal solutions inhibit the adsorption of heavy metal ions to the bacterial cell
      wall. However, the microbial sorbents reduced Ni(2+) levels in the mine-water
      used (93-100% Ni(2+) removal) to below the maximum acceptable limit of 350 MUg/l,
      established by the South African Bureau of Standards. Competition among metal
      ions for binding sites on the biomaterial surface can occur during the
      bioremediation process, but microbial sorption affinity for heavy metal ions can
      enhance their remediation in dilute (<5 mg/l heavy metal) wastewaters.

PMID- 21737200
TI  - Adsorption of copper(II) onto sewage sludge-derived materials via microwave
      irradiation.
AB  - The materials with adsorbent properties were produced from urban sewage sludge by
      two different procedures via microwave irradiation: (1) by one single pyrolysis
      stage (SC); (2) by chemical activation with ZnCl(2) (SZ). The BET, SEM and FT-IR
      have been used to evaluate the pore structural parameters and surface chemistry
      of the adsorbents, respectively. Subsequently they were used for adsorption of
      Cu(II) from aqueous solutions. The effects of various experimental parameters,
      such as pH, temperature were investigated in a batch-adsorption technique. The
      results showed that the adsorption of Cu(II) was maximal at pH 5.0. The kinetic
      study demonstrated that the adsorption process was followed the second-order
      kinetic equation. The experimental adsorption isotherm data were well fitted with
      Langmuir model and the maximum adsorption capacity of Cu(II) were found to be
      3.88 and 10.56 mg/g for SC and SZ, respectively, in the solution of pH 5.0.
      Thermodynamic parameters such as changes in the enthalpy (DeltaH(0)), entropy
      (DeltaS(0)) and free energy (DeltaG(0)) indicate that Cu(II) adsorption onto SC
      and SZ is an endothermic and spontaneous process in nature at 15-45 degrees C.
      These results indicate that the sewage sludge-derived material via microwave
      induced ZnCl(2) activation is an effective and alternative adsorbent for the
      removal of Cu(II) from aqueous solution.

PMID- 21737201
TI  - Comment on: Efficacy of botulinum toxin type A for treatment of persistent
      myofascial TMD pain: a randomized, controlled, double-blind multicenter study, by
      Ernberg, Hedenberg-Magnusson, List, and Svensson.

PMID- 21737203
TI  - A new direction for the fear avoidance model?

PMID- 21737202
TI  - Serotonin increases the functional activity of capsaicin-sensitive rat trigeminal
      nociceptors via peripheral serotonin receptors.
AB  - Peripheral serotonin (5HT) has been implicated in migraine and temporomandibular
      pain disorders in humans and animal models and yet the mechanism(s) by which 5HT
      evokes pain remains unclear. Trigeminal pain can be triggered by activation of
      the transient receptor potential V1 channel (TRPV1), expressed by a subset of
      nociceptive trigeminal ganglia (TG) neurons and gated by capsaicin, noxious heat,
      and other noxious stimuli. As 5HT is released in the periphery during
      inflammation and evokes thermal hyperalgesia, and TRPV1 is essential for thermal
      hyperalgesia, we hypothesized that 5HT increases the activity of capsaicin
      sensitive trigeminal neurons and that this increase can be attenuated by
      pharmacologically targeting peripheral 5HT receptors. TG cultures were pretreated
      with 5HT (10 nM-100 MUM), sumatriptan (5HT(1B/1D) agonist), ketanserin (5HT(2A)
      antagonist), granisetron (5HT(3) antagonist), or vehicle prior to capsaicin (30
      50 nM). Single-cell accumulation of intracellular calcium was recorded or
      calcitonin gene-related peptide (CGRP) release was measured following each
      treatment. In addition, using in situ hybridization and immunohistochemistry, we
      detected the colocalization of 5HT(1B), 5HT(1D), 5HT(2A), and 5HT(3A), but not
      5HT(2C) mRNA with TRPV1 in TG cells. 5HT pretreatment evoked a significant
      increase in calcium accumulation in capsaicin-sensitive trigeminal neurons and
      enhanced capsaicin-evoked CGRP release, but had no significant effect when given
      alone. Sumatriptan, ketanserin, and granisetron treatment attenuated calcium
      accumulation and 5HT enhancement of capsaicin-evoked CGRP release. Together these
      results indicate that 5HT increases the activity of capsaicin-sensitive
      peripheral nociceptors, which can be attenuated by pharmacologically targeting
      peripheral 5HT receptors, thereby providing a mechanistic basis for peripheral
      craniofacial pain therapy.

PMID- 21737204
TI  - Impaired mitochondrial energy production: the basis of pharmacoresistance in
      epilepsy.
AB  - Twenty to thirty percent of people who develop epilepsy continue to have seizures
      despite antiepileptic drug (AED) treatment. The introduction of many new AEDs in
      the last two decades does not appear to have reduced substantially the proportion
      of people who are pharmacoresistant and continue to have seizures. Currently
      there are two main mechanisms suggested for pharmacoresistance in people with
      epilepsy: the transporter and target hypothesis. There are inadequacies in both
      these hypotheses and alternatives should be considered. There is accumulating
      evidence from animal studies, human physiological measurements and imaging
      studies that there is impaired mitochondrial energy production in the
      epileptogenic zone. Impaired mitochondrial function and lower bioenergetic state
      is associated with higher extracellular glutamate and increased neuronal
      hyperexcitability. Conversely, the ketogenic diet effective in reducing seizures,
      has been shown in animal studies to be associated with up-regulation of
      mitochondrial genes and increased mitochondrial biogenesis. A human imaging study
      has also shown improved cerebral energy metabolism in people on a ketogenic diet.
      Hence, the hypothesis is that the likelihood of seizures occurring results mainly
      from the interplay of three factors: the seizuregenic potential of the epileptic
      focus, the efficacy of AEDs and the efficiency of mitochondrial function. This
      hypothesis can be tested by comparing mitochondrial function in people with
      epilepsy who are pharmacoresistant with those who have become seizure free. The
      implication of the hypothesis is that the management of epilepsy should take
      account of the many drugs, toxins, nutrition and lifestyle factors that are known
      to affect mitochondrial function.

PMID- 21737205
TI  - Obsessive Compulsive Disorder as a functional interhemispheric imbalance at the
      thalamic level.
AB  - Obsessive Compulsive Disorder (OCD) involves failures in two main inhibitory
      processes, namely cognitive (obsessions) and behavioral (compulsions). Recent
      research has supported two cortical-subcortical pathways on OCD pathogenesis: (a)
      the frontostriatal loop (dorsolateral-caudate-striatum-thalamus) responsible for
      impairments of behavioral inhibition; (b) the orbitofrontal loop (orbitofrontal,
      medial prefrontal and cingulate) responsible for impairments with cognitive
      inhibitory processes. These failures in both cognitive and motor inhibitory
      systems may mediate several neuropsychological deficits in these patients, namely
      memory, attention, planning and decision making. But are those deficits related
      to specific hemispheric effects, namely functional imbalance between hemispheres?
      In this article we hypothesize that: (1) OCD patients have an inter-hemispheric
      functional imbalance, probably due to inadequate filtering at the thalamic level;
      (2) the restoration of inter-hemispheric balance, will be correlative to
      symptomatic improvement.

PMID- 21737206
TI  - Misleading conclusion from the unifying theory of the stellate ganglion block for
      the treatment of posttraumatic stress disorder.

PMID- 21737207
TI  - Evaluation of a dehydrated beef protein to replace sodium-based phosphates in
      injected beef strip loins.
AB  - A dehydrated beef protein (DBP) was evaluated as a replacement for the phosphate
      added to beef injection brines. U.S. Select strip loins (n=20) were injected to
      110% of their initial weight with a brine containing 3.6% salt and 4.5% sodium
      phosphate (CON) or 3.6% salt and 5% dehydrated beef protein (DBP). DBP loins had
      less fluid loss after 30 min. Steaks from both treatments lost similar amounts of
      fluid during storage. Total fluid loss was lower for DBP injected product. Lipid
      oxidation (TBARS) products were 0.23-0.60 mg/Kg higher for DBP steaks. DBP steaks
      were slightly less red than CON steaks according to instrumental measurements.
      Sensory panel evaluation, however, indicated no differences in redness. DBP
      steaks were less tender according to trained sensory panel. Results indicated the
      DBP to be effective in increasing brine retention and a viable alternative to
      phosphates when used in brines injected into beef strip steaks.

PMID- 21737208
TI  - The evolution of lean beef: identifying lean beef in today's U.S. marketplace.
AB  - Changes in cattle breeding and management coupled with extensive trimming of
      visible fat from retail cuts have resulted in the wide-spread availability of
      lean beef to U.S. consumers. Despite these changes, there is limited awareness
      regarding the reduced total fat content and the favorable fatty acid profile of
      beef. Relative to the calories it contributes, the impact of beef on the
      nutritional quality of the American diet via its contribution of protein and
      certain key micronutrients is often under appreciated. The following discussion
      documents the progressive reduction in fat content of U.S. beef during the past
      30 years, highlights ongoing efforts to update United States Department of
      Agriculture nutrient data for beef, and summarizes findings from randomized
      controlled trials of beef and plasma lipid outcomes. Beef is a popular, nutrient
      dense food and the availability of at least 29 lean cuts of beef in the U.S.
      marketplace can help consumers meet their cardiovascular health goals.

PMID- 21737209
TI  - Effect of season on contractile and metabolic properties of desert camel muscle
      (Camelus dromedarius).
AB  - Thirty fattened one humped desert camels were used to examine the effect of
      season on contractile and metabolic properties of Longissimus thoracis (LT)
      muscle. Ten camels were slaughtered according to seasons of the year (winter,
      summer and autumn). Season significantly influenced muscle chemical composition,
      ultimate pH (pHu) and color. Activities of metabolic enzymes were higher during
      autumn season compared to summer and winter for phosphofructokinase (+64%
      compared to both seasons) and for isocitrate dehydrogenase (+35% and +145% in
      autumn vs. summer and winter, respectively). Quantification of muscle myosin
      heavy chain isoforms by SDS-PAGE electrophoresis showed only presence of type I
      and type IIa MyHC in camel muscle and indicated high proportion in winter for
      type I and in autumn for type IIa with respect to other seasons. Several
      correlations between different MyHC proportions and enzyme activities were
      reported. These findings indicated that muscle characteristics in camels are
      influenced by season.

PMID- 21737210
TI  - Steinmann pin arthrodesis for salvage of failed small joint arthroplasty.
AB  - Proximal interphalangeal joint arthroplasty has been performed since the 1960s,
      with good short-term and medium-term results. However, despite improvements in
      pain, there is a considerable failure rate. Often, there is a delicate soft
      tissue envelope and substantial bone loss after removal of these prostheses,
      making salvage procedures difficult. We present an intramedullary technique of
      proximal interphalangeal joint arthrodesis following failed implant arthroplasty.
      This technique has provided reliable results in a small cohort of patients.

PMID- 21737211
TI  - Imaging features of chronic expanding hematoma in the soft tissues of the hand
      simulating an aggressive lesion: case report.
AB  - A chronic expanding hematoma can persist and increase in volume for more than 1
      month after the first hemorrhage. It is rare, uncommon in the hand, little known
      among physicians, and an imitator of malignancy. Our purpose was to report a case
      of this condition in the soft tissues of an 8-year-old girl's hand that simulated
      an aggressive lesion, and to conduct a review on this subject.

PMID- 21737212
TI  - [Hematogenous dissemination in epithelial ovarian cancer: case report].
AB  - Epithelial carcinomas represent 80% of cancers. Dissemination of ovarian
      epithelial cancers is usually peritoneal and rarely hematogenous. The case at
      hand concerns the hematogenous transmission of an ovarian epithelial cancer with
      cystic rectal metastasis. The cytology test shows no evidence of peritoneal
      carcinomatosis. The immunohistochemistry test confirms the primary ovarian cancer
      with rectal metastasis and the presence of vascular emboli. This clinical study
      describes one of the rare forms of dissemination of epithelial cancers.
      Hematogenous transmission should not be confused with dissemination through
      accessory lymphatic routes.

PMID- 21737213
TI  - [Epidemiology, characterization of genotypes of human papillomavirus in a
      population of women in Ouagadougou].
AB  - OBJECTIVES: This work was carried out in order to determine the prevalence of
      different HPV genotypes in a population of women attending gynecological
      consultation. MATERIAL AND METHODS: From May to June 2010, cervical samples were
      obtained from 300 women attending gynecological consultation in two health
      centers in Ouagadougou. The strains of HPV genotyping was done using the
      technique of polymerase chain reaction (PCR) followed by reverse hybridization on
      nitrocellulose strips. RESULTS: Among the 73 women(24.3%) infected with HPV, only
      27.4% (20/73) of them were infected with a HPV low risk (BR), the 72.6% (53/73).
      Other women were infected with at least one high risk HPV (HR). By combining the
      HPV genotypes found without taking into account the number of infected women, we
      found a total of 84 HPV among whom we have high-risk HPV : HPV-50'S(26/84 or
      31.0%), HPV-18 (12/84 or 14.3%), HPV-16 (9/84 or 10.7%), HPV-30'S (5/84 or 5.9%),
      HPV-HR (5/84 or 5.9%) and HPV-45 (3/84 or 3.6%) and low-risk HPV: HPV-6 (15/84 or
      17.9%) and HPV-BR (9/84 or 10.7%). We have found no HPV-11. DISCUSSION AND
      CONCLUSION: The prevalence of HPV found in our series is comparable to that found
      in the world. To complete this study, it would be necessary to investigate the
      prevalence of HPV found in cervical lesions in Burkina Faso.

PMID- 21737214
TI  - Physiological and subjective effects of acute intranasal methamphetamine during
      extended-release alprazolam maintenance.
AB  - BACKGROUND: Medications development for methamphetamine dependence is ongoing,
      but no widely accepted, effective pharmacotherapy has been identified. Previous
      studies have demonstrated neurobiological perturbations to central GABA(A)
      activity following chronic stimulant use, and that positive modulation of GABA(A)
      receptors attenuates the neurochemical and behavioral response to stimulant drugs
      such as methamphetamine. Therefore, GABA(A) modulators could be useful as
      pharmacotherapies for stimulant-use disorders. METHODS: This study tested the
      hypothesis that intranasal methamphetamine would be safe and well tolerated
      during maintenance on extended-release alprazolam (XR), and that the effects of
      methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant
      dependent individuals completed an inpatient experiment in which ascending doses
      of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after
      four days of alprazolam XR maintenance (0 and 1mg/day). RESULTS: Intranasal
      methamphetamine produced prototypical effects (e.g., increased positive
      subjective ratings and elevated cardiovascular signs). The combination of
      intranasal methamphetamine and alprazolam XR was safe and well tolerated.
      Alprazolam XR produced small, but orderly, reductions in some of the subjective
      effects of methamphetamine, and performance impairment. CONCLUSIONS: The present
      results demonstrate that methamphetamine use during alprazolam XR treatment would
      not pose a significant safety risk. Given the potential of GABA(A) positive
      modulators to manage certain aspects of stimulant abuse and dependence (i.e.,
      drug-induced seizures, anxiety and stress), but the relatively small impact on
      the acute abuse-related effects of methamphetamine observed here, additional
      research with GABA(A) positive modulators is warranted, but should consider their
      use as an adjunct component of combination behavioral and/or drug treatment.

PMID- 21737215
TI  - Quantitative assessment of time dependent drug-use trends by the analysis of
      drugs and related metabolites in raw sewage.
AB  - BACKGROUND: Accurate and timely information on the scale and dynamics of drug
      consumption is important for assessing the needs of law enforcement and public
      health services in a community. AIMS: This paper presents a detailed examination
      of a comprehensive sewage-sampling campaign for the purposes of increasing an
      understanding of the dynamics of drug-flows in sewage streams, and developing new
      methodology by which this technique can support traditional drug-use surveys.
      METHODS: A total of 104 sewage samples were collected from a treatment plant
      servicing approximately 500000 people and analysed for levels of methamphetamine,
      cocaine and cocaine metabolites. Careful examination of the kinetics of drug-flow
      profiles was then performed in order to identify trends or patterns of use within
      the community. RESULTS: Results were validated against identical measurements of
      pharmaceutical reference compounds. Consumption profiles for cocaine and
      methamphetamine were found to differ in terms of frequency and timing of use. The
      majority of cocaine consumption occurs during the evening hours and 45% of
      consumption of this drug occurs in weekend periods. The flow of methamphetamine
      in the sewage system appears more evenly spread throughout the week. CONCLUSIONS:
      This result is consistent with both an extended excretion half-life and a pattern
      of use that is more evenly balanced across all days of the week. Comprehensive
      investigation in to the scale and kinetics of drug flow in a sewage stream can
      therefore provide valuable information, not only in terms of the volume of drug
      consumed, but also in terms of identifying differing usage-patterns over daily
      and weekly time-scales.

PMID- 21737216
TI  - Haemophilus parasuis exhibits IgA protease activity but lacks homologs of the IgA
      protease genes of Haemophilus influenzae.
AB  - Haemophilus parasuis, the bacterium responsible for Glasser's disease, is a
      pathogen of significant concern in modern high-health swine production systems
      but there is little information regarding the identity or function of its
      virulence factors. Several important human mucosal pathogens, including the
      closely related bacterium Haemophilus influenzae, utilize IgA proteases to aid in
      defeating the host immune response and facilitate disease but it is unknown
      whether H. parasuis synthesizes any product with IgA protease activity. To
      investigate potential virulence mechanisms of H. parasuis, we evaluated five
      strains for their ability to digest purified IgA. Western blotting demonstrated
      cleavage of swine IgA, but not human IgA1, following incubation with culture
      supernatants from three strains, two of which are known to cause invasive
      disease. No genes with homology to the H. influenzae IgA protease genes iga and
      igaB could be identified in any H. parasuis strain using either PCR or Southern
      blotting. These results demonstrate that a novel IgA protease produced by some
      strains of H. parasuis cleaves the swine IgA heavy chain at a site not found in
      human IgA1.

PMID- 21737217
TI  - Sources of spermatozoa loss during collection and artificial insemination of
      horses.
AB  - During artificial insemination of horses, it is important to accurately estimate
      the number of spermatozoa in each insemination dose. However, little research
      exists regarding sources of spermatozoa loss during collection and artificial
      insemination. Therefore, spermatozoal losses were quantified in the dismount loss
      (187.6*10(6)+/-62.5*10(6)spermatozoa), gel fraction (179.8*10(6)+/
      61.7*10(6)spermatozoa), and the collection receptacle (136.1*10(6)+/
      26.9*10(6)spermatozoa). Spermatozoal losses were examined in the centrifuge tube
      (25.8*10(6)+/-2.1*10(6)spermatozoa), AI pipette during the air removal
      (90.9*10(6)+/-8.5*10(6)spermatozoa), and spermatozoa remaining in the AI pipette
      after insemination (342.9*10(6)+/-21.4*10(6)spermatozoa). The average cumulative
      loss was 14.2+/-2.9% of the total spermatozoa ejaculated with approximately half
      of the loss due to the process of semen collection and half due to the process of
      artificial insemination. Spermatozoa retained in the AI pipette, after
      insemination with extended semen, represented the greatest source of loss.

PMID- 21737218
TI  - Factors determining yield and quality of illicit indoor cannabis (Cannabis spp.)
      production.
AB  - Judiciary currently faces difficulties in adequately estimating the yield of
      illicit indoor cannabis plantations. The latter data is required in penalization
      which is based on the profits gained. A full factorial experiment in which two
      overhead light intensities, two plant densities and four varieties were combined
      in the indoor cultivation of cannabis (Cannabis spp.) was used to reveal cannabis
      drug yield and quality under each of the factor combinations. Highest yield was
      found for the Super Skunk and Big Bud varieties which also exhibited the highest
      concentrations of Delta(9)-tetrahydrocannabinol (THC). Results show that plant
      density and light intensity are additive factors whereas the variety factor
      significantly interacts with both plant density and light intensity factors.
      Adequate estimations of yield of illicit, indoor cannabis plantations can only be
      made if upon seizure all factors considered in this study are accounted for.

PMID- 21737219
TI  - Investigation of hydrogen cyanide generation from the cyanoacrylate fuming
      process used for latent fingermark detection.
AB  - Cyanoacrylate fuming is one of the most common techniques employed for the
      detection of latent fingermarks on non-porous surfaces such as plastic and glass.
      The technique is generally applied by exposing items of interest to the vapours
      generated by heating a suitable quantity of commercial cyanoacrylate adhesive. In
      this study, the potential for highly toxic hydrogen cyanide (HCN) to be generated
      from the overheating of cyanoacrylate was investigated. Two commercial
      cyanoacrylate adhesives and two quantitative methods for the determination of HCN
      were employed: (i) the sodium picrate method; and (ii) the picrate-resorcinol
      method. (13)C nuclear magnetic resonance (NMR) analysis was used to confirm the
      presence of cyanide. In addition, the thermal decomposition of cyanoacrylate was
      studied using simultaneous thermogravimetric and differential thermal analysis
      (TGA-DTA). It was determined that detectable and quantifiable amounts of HCN were
      generated from the thermal decomposition of cyanoacrylate monomer and polymer at
      temperatures as low as 200  degrees C. Using an optimised picrate-resorcinol
      method, it was shown that around 10 MUg of HCN could be generated from the
      heating of 1g of cyanoacrylate monomer at 200  degrees C. For one of the
      adhesives tested, this increased to above 100 MUg of HCN when 1g of cyanoacrylate
      monomer was heated at 280  degrees C. Recommendations are provided that, if
      followed, should ensure that the cyanoacrylate fuming process can be safely
      applied with minimal risk to the operator.

PMID- 21737220
TI  - Contrast-enhanced ultrasound study of primary hepatic angiosarcoma: a pitfall of
      non-enhancement.
AB  - OBJECTIVE: To investigate the contrast-enhanced ultrasound (CEUS) characteristics
      of primary hepatic angiosarcoma (PHA). METHODS: The sonographic findings and CEUS
      images of PHA in three patients were retrospectively analyzed. RESULTS: In our
      study, 3 cases of PHA (2 multiple nodules and 1 solitary mass) showed similar
      enhancement pattern on CEUS, characterized by remarkable central non-enhancement
      and peripheral irregular enhancement in the arterial and portal phase, and
      complete wash-out in the late phase. Furthermore, we unexpectedly found that
      abundant neoplastic tissues were present in the central area of non-enhancement
      on pathological evaluation. Based on literature review, we supposed that the
      unusual finding may be associated with the very low velocity of blood flow in the
      central region of tumors. CONCLUSION: CEUS could well depict PHA with some common
      features, which may provide valuable clues in diagnosis of this rare disease. And
      non-necrotic tumor tissue of PHA could also demonstrate non-enhancement on CEUS,
      which warrant further investigations.

PMID- 21737221
TI  - A fast liquid chromatography-tandem mass spectrometry method for determining
      benzodiazepines and analogues in urine. Validation and application to real cases
      of forensic interest.
AB  - A fast liquid chromatographic/tandem mass spectrometric method was developed for
      the simultaneous determination in human urine of seventeen benzodiazepines, four
      relevant metabolites together plus zolpidem and zopiclone. The sample
      preparation, optimized to take into account the matrix effect, was based on
      enzymatic hydrolysis and liquid-liquid extraction. The separation of the twenty
      three analytes was achieved in less than eight minutes. The whole methodology was
      fully validated according to UNI EN ISO/IEC 17025:2005 rules and 2006 SOFT/AAFS
      guidelines. Selectivity, linearity range, identification (LOD) and quantitation
      (LOQ) limits, precision, accuracy and recovery were evaluated. For all the
      species the signal/concentration linearity was satisfactory in the 50-1000 ng/mL
      concentration range. The limits of detection ranged from 0.5 to 30 ng/mL and LOQs
      from 1.7 to 100.0 ng/mL. Precisions were in the ranges 5.0-11.8%, 1.5-11.0% and
      1.1-4.4% for low (100 ng/mL), medium (300 ng/mL) and high (1000 ng/mL)
      concentration, respectively. The accuracy, expressed as bias% was within +/- 25 %
      for all the analytes. The recovery values, evaluated at 300 ng/mL concentration,
      ranged from 56.2% to 98.8%. The present method for the determination of several
      benzodiazepines, zolpidem and zopiclone in human urine proved to be simple, fast,
      specific and sensitive. The quantification by LC-MS/MS was successfully applied
      to 329 forensic cases among driving re-licensing, car accidents and alleged
      sexual violence cases.

PMID- 21737222
TI  - Improving door-to-antibiotic time in severely septic emergency department
      patients.
AB  - BACKGROUND: The Surviving Sepsis Campaign (SSC) guidelines recommend that broad
      spectrum antibiotics be administered to severely septic patients within 3 h of
      emergency department (ED) admission. Despite the well-established evidence
      regarding the benefit of timely antibiotics, adoption of the SSC recommendation
      into daily clinical practice has been slow and sporadic. STUDY OBJECTIVE: To
      study the impact of storing broad-spectrum antibiotics in an ED automated
      dispensing cabinet (ADC) on the timeliness of antibiotic administration in
      severely septic patients presenting to the ED. METHODS: Retrospective
      observational study of timeliness of antibiotic administration in severely septic
      patients presenting to a community ED before and after adding broad-spectrum
      antibiotics to the ED ADC. Data on 56 patients before and 54 patients after the
      intervention were analyzed. The primary outcome measure was mean order-to
      antibiotic time. Secondary outcome measures included mean door-to-antibiotic time
      and percentage of patients receiving antibiotics within 3 h. RESULTS: The final
      analysis was on 110 patients. Order-to-antibiotic administration time was reduced
      by 29 min post-intervention (55 min vs. 26 min, 95% confidence interval [CI] 12.5
      45.19). Mean door-to-antibiotic time was also reduced by 70 min (167 min vs. 97
      min, 95% CI 37.53-102.29). The percentage of severely septic patients receiving
      antibiotics within 3h of arrival to the ED increased from 65% pre-intervention to
      93% post-intervention (95% CI 0.12-0.42). CONCLUSION: Storing key antibiotics in
      an institution's severe sepsis antibiogram in the ED ADC can significantly reduce
      order-to-antibiotic times and increase the percentage of patients receiving
      antibiotics within the recommended 3 h of ED arrival.

PMID- 21737223
TI  - Abdominal pain and new-onset seizures.

PMID- 21737224
TI  - Medial thigh abscess mimicking septic arthritis of the knee: a report of two
      cases.
AB  - BACKGROUND: Septic arthritis of the knee joint requires prompt diagnosis and
      treatment for optimal outcomes. Pyomyositis with abscess formation is uncommon
      but may present with similar symptoms in the vicinity of a joint. OBJECTIVE: This
      report describes two cases of medial thigh abscess initially diagnosed and
      treated as septic arthritis, and highlights the need to make an accurate
      diagnosis. CASE REPORT: Two patients presenting with knee pain secondary to
      pyomyositis and abscess formation in the medial thigh were investigated with
      aspiration and treated subsequently with knee surgery, resulting in contamination
      of the knee joint in one case and delayed diagnosis with significant morbidity in
      both. CONCLUSION: Failure to identify a soft tissue infection may lead to delayed
      diagnosis, misdirected treatment, and contamination of a normal joint. Diagnosis
      is best confirmed with thorough physical examination and specific imaging where
      available.

PMID- 21737225
TI  - Denture aspiration within trachea during seizure.

PMID- 21737226
TI  - Personal experiences of taking part in clinical trials - a qualitative study.
AB  - OBJECTIVE: To investigate people's experiences of and attitudes to participation
      in clinical trials. METHODS: 42 in-depth qualitative interviews, covering
      different types of trial and intervention, analysed thematically using a modified
      grounded theory approach. RESULTS: Many participants argued for a right to
      participate in research. This may be partly because personal benefit was a common
      primary motivation for taking part - but the benefits cited were not only
      personal health outcomes. Whilst most were satisfied with information received,
      some felt it was too complex. Gaps in understanding were evident, especially
      around randomisation, but trust in trial staff was high. Desire for feedback of
      trial results was common. CONCLUSION: Unintended consequences may arise from
      efforts to give full information and challenge therapeutic misconceptions. People
      wanted 'enough' information to help them decide, but their definition of
      'enough', and the relative importance of written information versus
      discussion/advice from trusted professionals, varied by individual. In seeking to
      minimise misunderstanding we stress uncertainty and risk but have perhaps lost
      sight of the value people derive from trial participation. PRACTICE IMPLICATIONS:
      Better information on trial availability, shorter trial leaflets and greater
      emphasis on face-to-face discussion are suggested. Recruitment literature could
      appeal to a wider range of benefits.

PMID- 21737227
TI  - Validation of the Joensuu risk criteria for primary resectable gastrointestinal
      stromal tumour - the impact of tumour rupture on patient outcomes.
AB  - BACKGROUND: Approval of imatinib for adjuvant treatment of gastrointestinal
      stromal tumours (GIST) raised discussion about accuracy of prognostic factors in
      GIST and the clinical significance of the available risk stratification criteria.
      METHODS: We studied the influence of a new modification of the NIH Consensus
      Criteria (the Joensuu risk criteria), NCCN-AFIP criteria, and several
      clinicopathological factors, including tumour rupture, on relapse-free survival
      (RFS) in a prospectively collected tumour registry series consisting of 640
      consecutive patients with primary, resectable, CD117-immunopositive GIST. The
      median follow-up time after tumour resection was 39 months. None of the patients
      received adjuvant imatinib. RESULTS: The median RFS time after surgery was 50
      months. In univariable analyses, high Joensuu risk group, tumour mitotic count
      >5/50 HPF, size >5 cm, non-gastric location, tumour rupture (7% of cases; P =
      0.0014) and male gender had adverse influence on RFS. In a multivariable analysis
      mitotic count >5/50HPF, tumour size >5 cm and non-gastric location were
      independent adverse prognostic factors. Forty, 151, 86 and 348 patients were
      assigned according to the Joensuu criteria to very low, low, intermediate and
      high risk groups and had 5-year RFS of 94%, 94%, 86% and 29%, respectively.
      CONCLUSION: The Joensuu criteria, which include 4 prognostic factors (tumour
      size, site, mitotic count and rupture) and 3 categories for the mitotic count,
      were found to be a reliable tool for assessing prognosis of operable GIST. The
      Joensuu criteria identified particularly well high risk patients, who are likely
      the proper candidates for adjuvant therapy.

PMID- 21737228
TI  - Molecular chaperones: toward new therapeutic tools.
AB  - Molecular chaperones (or heat shock proteins) are evolutionarily conserved and
      essential proteins that play a key role in cell survival through cytoprotective
      mechanisms. Despite their possible clinical applications, the understanding of
      these structures is still quite limited. The aim of the present study is to
      review the literature to understand the physiological importance, implication in
      various diseases (especially in cancer and neurodegenerative diseases), possible
      applicability, and future prospects of heat shock proteins. The cytoprotective
      mechanisms of molecular chaperones can be co-opted by oncogenic processes
      favoring tumor growth, invasion, evasion of apoptosis, and metastasis, thus
      making inhibitors to these molecules possible therapeutic options for cancer
      patients. However, there is also evidence showing that upregulation of heat shock
      proteins can have an antineoplastic effect through immunomodulatory activity.
      This is why chaperones have already been investigated for conventional
      chemotherapy under specific conditions, yielding interesting results. The
      induction of heat shock protein activity is also of potential benefit in many
      other diseases where structural and functional preservation of proteins may
      enhance cell survival, including neurodegeneration, trauma, stroke, and
      cardiovascular disease. In addition, the immune properties of chaperones can
      potentially be exploited for such diseases as diabetes, atherosclerosis, and
      other chronic inflammatory conditions. Thus, continuing efforts to clarify the
      role of chaperones may guide the development of new therapeutic modalities
      capable of minimizing the impact of diseases such as cancer, heart disease, and
      diabetes as well as obtaining better results in neurological conditions currently
      lacking alternative treatments.

PMID- 21737229
TI  - Antiphase signalling in the neuroendocrine-immune system in healthy humans.
AB  - BACKGROUND: Any quantity varying in the spatial-temporal dimension may be
      considered as a signal. Human lymphocyte cell surface molecules and subsets
      present circadian variation and this variation may represent a kind of signalling
      in the neuroendocrine-immune system. We have analyzed the dynamics of variation
      of specific lymphocyte subsets in healthy humans. SUBJECTS AND METHODS: In our
      study, lymphocyte subpopulation analyses were performed and cortisol, melatonin,
      GH and TSH serum levels were measured on blood samples collected every 4h for 24
      hours from eleven healthy men, ages 35-53 years (mean=44+/-6SD). RESULTS: A clear
      circadian rhythm was validated for CD8 and cortisol with acrophase during the day
      and for CD3, CD4, melatonin, GH and TSH with acrophase at night. Cross
      correlation showed that CD3 correlated positively with CD4 (rho=0.67, P<0.05) and
      negatively with CD8 (rho=-0.41, P<0.05), CD4 correlated positively with melatonin
      (rho=0.90, P<0.05), GH (rho=0.92, P<0.05) and TSH (rho=0.71, P<0.05), negatively
      with CD8 (rho=-0.90, P<0.05) and cortisol (rho=-0.18, P<0.05), CD8 correlated
      positively with cortisol (rho=0.38, P<0.05). DISCUSSION: The different profiles
      of nyctohemeral changes of lymphocyte cell surface molecules and specific
      lymphocyte subsets realize different relationships with the neuroendocrine
      hormones and might represent a way of signal transmission among the multiple
      components of the neuroendocrine-immune system.

PMID- 21737230
TI  - [Utility of the bone marrow biopsy in the diagnosis of essential thrombocytemia].
AB  - INTRODUCTION: The recent discovery of the Janus Kinase 2 (JAK2(V617F)) mutation,
      an indicator of clonal expansion, has widely modified the diagnostic work-up of
      myeloproliferative disorders. However, histopathologic criteria of the WHO
      classification, focused on megakaryocytes abnormalities, have taken a central
      role in the diagnosis of essential thrombocytemia (ET), particularly to
      distinguish it from the prefibrotic myelofibrosis (PMF) evolving to a clinic
      myelofibrosis unlike true ET. The aim of our study is to evaluate inter-observer
      reproducibility and prognostic implications of these pathological criteria
      comparing diagnoses with clinical and biological follow-up. METHODS: Forty-four
      patients presenting with isolated thrombocytemia were retrospectively evaluated.
      All patients were initially diagnosed with ET based on the PVSG classification
      from 1997. The initial bone marrow biopsy specimens were re-evaluated using the
      Thiele pathological classification: true ET, prefibrotic myelofibrosis (PMF) and
      early myelofibrosis. Patients were followed for a median of 6 years. RESULTS: Our
      population includes three patients with polycythemia vera and 41 patients with
      true ET. Based on clinical and biological follow-up, diagnoses were changed to
      idiopathic myelofibrosis in four of six patients with "early" myelofibrosis
      (66.7%), but in only one of 14 patients with PMF (7.15%). In contrast, the
      diagnosis of true ET was not changed in the 21 cases. Inter-observer
      reproducibility for pathological classification was 100%. CONCLUSION: In this
      study, our diagnostic methodology based on the clinico-biological follow-up,
      which has not been evaluated in previous studies, calls into question the
      diagnostic value of the pathological criteria in PMF.

PMID- 21737231
TI  - [Basic calcium phosphate crystal deposition disease].
AB  - Hydroxyapatite crystals are a common cause of periarticular disease. Virtually,
      any joint can be involved, but the shoulder is by far most commonly involved.
      These calcifications, often asymptomatic, can lead to an acute microcrystalline
      tendinitis or bursitis, which may simulate infection. The diagnosis of
      periarticular calcifications relies on imaging techniques using X-rays or
      ultrasounds. Treatment of acute tendinitis or bursitis includes icing, rest,
      analgesics or non steroidal anti-inflammatory drug and oral steroids or local
      steroids injection. Removal of the deposit can be considered in patients with
      chronic pain, particularly at the shoulder.

PMID- 21737232
TI  - Severe protein C deficiency is associated with organ dysfunction in patients with
      severe sepsis.
AB  - PURPOSE: The aim of this study was to assess the relationship between protein C
      levels and temporal changes in organ dysfunction. MATERIALS AND METHODS: Using
      data from the placebo arm of Recombinant Human Activated PROtein C Worldwide
      Evaluation in Severe Sepsis trial (N = 775), we compared the development of organ
      dysfunction over time, in adult severe sepsis patients with and without severe
      protein C deficiency. RESULTS: At study enrollment (baseline), patients with and
      without severe protein C deficiency were similar in age and likelihood of
      comorbidities. Patients with severe protein C deficiency had lower arterial blood
      pressure (P = .0006), greater serum creatinine concentration (P < .0001),
      elevated markers of thrombosis and inflammation, and impairment of fibrinolysis
      (P < .0001). The baseline PaO(2)/FiO(2) ratio was not significantly different
      between the 2 groups. Seven days after study enrollment, cardiovascular and renal
      function remained significantly worse in patients with severe protein C
      deficiency (P < .0001), and respiratory dysfunction was greater (P < .0001).
      Baseline protein C deficiency was seen to be associated with subsequent
      pulmonary, renal, and hematologic organ failure. CONCLUSIONS: Severe protein C
      deficiency in patients with severe sepsis is associated with both the incidence
      and severity of organ dysfunction and subsequent worsening of organ function and
      may be a useful predictor of organ failure in severe sepsis.

PMID- 21737233
TI  - Does intensive care unit severity of illness influence recall of baseline
      physical function?
AB  - PURPOSE: The aim of this study is to evaluate if severity of illness in the
      intensive care unit influences patients' retrospective recall of their baseline
      physical function from before hospital admission. MATERIALS AND METHODS: This is
      a prospective cohort study of 193 acute lung injury survivors who, before
      hospital discharge, retrospectively reported their prehospitalization physical
      function using the Short Form 36 quality of life survey. RESULTS: Four measures
      were used to evaluate intensive care unit (ICU) severity of illness: (1) Acute
      Physiology and Chronic Health Evaluation II Acute Physiologic Score at ICU
      admission, (2) Lung Injury Score at acute lung injury diagnosis, (3) Sequential
      Organ Failure Assessment score at study enrollment, and (4) maximum daily
      Sequential Organ Failure Assessment score during the entire ICU stay. In
      multivariable linear regression analysis, no measure of severity of illness was
      associated with prehospitalization physical function. Education level
      significantly modified the relationship between ICU severity of illness and
      baseline physical function with lower educational attainment having a stronger
      association with baseline physical function. CONCLUSION: Intensive care unit
      severity of illness was not associated with patients' retrospectively recalled
      baseline physical function. Patients with a lower level of education may be more
      influenced by ICU severity of illness, but the magnitude of this effect may not
      be clinically meaningful.

PMID- 21737234
TI  - Nonhematological organ dysfunction and positive fluid balance are important
      determinants of outcome in adults with severe dengue infection: a multicenter
      study from India.
AB  - PURPOSE: The purpose of the study was to explore determinants of outcome in
      adults with dengue hemorrhagic fever or dengue shock syndrome. METHODS: We
      performed a multicenter, retrospective, observational study over a 2-year period
      in 3 intensive care units (ICUs) in Pune (India). RESULTS: One hundred eighty
      four adult patients were admitted to the ICU with a positive dengue
      immunoglobulin M test result; 43 met the World Health Organization criteria for
      dengue hemorrhagic fever or dengue shock syndrome. One patient who was
      transferred to another hospital and whose outcome was unknown was not included in
      the analysis. Of the 42 patients, 20 (48%) had multiorgan failure on ICU
      admission. The ICU mortality was 19% (8/42). Nonsurvivors were more likely than
      survivors to have cardiovascular (100% vs 12%), respiratory (88% vs 12%), or
      neurological (75% vs 12%) failure (all P < .01). Hematological failure was not
      associated with a higher risk of death. Cumulative fluid balance at 72 hours was
      more positive in nonsurvivors than in survivors (6.2 vs 3.5 L, P < .05). Serum
      albumin concentrations at ICU admission were lower in nonsurvivors than in
      survivors (2.9 +/- 0.3 vs 3.4 +/- 0.7 g/dL, P < .05). CONCLUSIONS: In our cohort,
      outcome from severe dengue was primarily related to nonhematological organ
      failure. Low serum albumin concentration on ICU admission and a more positive
      fluid balance at 72 hours were also associated with worse outcomes.

PMID- 21737235
TI  - Efficacy and cardiovascular tolerability of continuous veno-venous
      hemodiafiltration in acute decompensated heart failure: a randomized comparative
      study.
AB  - BACKGROUND AND OBJECTIVES: Recently, continuous veno-venous hemodiafiltration
      (CVVHDF) has received increased attention in the treatment of congestive heart
      failure (CHF). The aim of this study is to assess the safety and efficacy of
      CVVHDF compared with intravenous furosemide in patients with CHF. METHODS: Forty
      patients having CHF were included in this prospective, randomized, comparative
      trial. We randomized patients to treatment for 72 hours with CVVHDF or
      intravenous furosemide. Outcomes assessed were weight loss, total fluid output,
      length of stay (LOS) in the intensive care unit (ICU), 30-day mortality, and
      cardiovascular stability. RESULTS: Demographic data were comparable in both
      groups. Weight loss (P <= .05) and total fluid output (P <= .01) were greater in
      the CVVHDF group. Length of stay in the ICU was significantly reduced in the
      CVVHDF group (P <= .05). The mortality rates were comparable in both groups. The
      cardiac output and the stroke volume significantly increased, whereas the
      pulmonary capillary wedge pressure significantly decreased (P <= .05) in both
      groups compared with the baseline. A transient attack of hypotension occurred in
      1 patient in the CVVHDF group. CONCLUSION: In CHF, the use of CVVHDF effectively
      and safely produced greater weight and fluid loss and decreased LOS in the ICU
      more than the intravenous furosemide with no hemodynamic instability.

PMID- 21737236
TI  - Relationship between the timing of administration of IgM and IgA enriched
      immunoglobulins in patients with severe sepsis and septic shock and the outcome:
      a retrospective analysis.
AB  - PURPOSE: Because the use of IgM and IgA enriched polyclonal intravenous
      immunoglobulins (eIg) is a standard of care in critically ill patients admitted
      to our intensive care unit (ICU) with the diagnosis of severe sepsis or septic
      shock, we investigated if the delay from the onset of severe sepsis and septic
      shock and their administration could influence the outcome. MATERIALS AND
      METHODS: The medical records of all patients with severe sepsis or septic shock
      admitted to our ICU from July 2004 through October 2009 and treated with eIg
      (Pentaglobin(r); Biotest, Dreieich, Germany) were retrospectively examined.
      RESULTS: A total of 129 adult patients with severe sepsis or septic shock were
      considered eligible. Thirty-two percent of patients died during the ICU stay.
      Survivors were given eIg significantly earlier than nonsurvivors (23 vs 63 hours,
      P < .05). The delay in the administration of eIg and the Simplified Acute
      Physiology Score II were the only variables that entered stepwise a propensity
      score-adjusted logistic model. The delay in the administration of eIg was a
      significant predictor of the odds of dying during the ICU stay (odds ratio for 1
      hour of delay, 1.007; P < .01; 99% confidence interval from 1.001 to 1.010) and
      proved to be independent from the Simplified Acute Physiology Score II and other
      variables. CONCLUSIONS: The efficacy of eIg, being maximal in early phases of
      severe sepsis and/or septic shock, is probably time dependent.

PMID- 21737237
TI  - Comparison of CAM-ICU and ICDSC for the detection of delirium in critically ill
      patients focusing on relevant clinical outcomes.
AB  - PURPOSE: Delirium is a frequent and serious problem in the intensive care unit
      (ICU) that is associated with increased mortality, prolonged mechanical
      ventilation, and prolonged hospital length of stay (LOS). The main objective of
      the present study was to compare and assess the agreement between the diagnosis
      of delirium obtained by the Confusion Assessment Method for the ICU (CAM-ICU) and
      Intensive Care Delirium Screening Checklist (ICDSC) in patients admitted to the
      ICU and their association with outcomes. METHODS: Adult patients admitted to the
      ICU for more than 24 hours between May and November 2008 were included. Patients
      with a Richmond Agitation-Sedation Scale score of -4 to -5 for more than 3 days
      were excluded. Delirium was evaluated twice a day by the ICDSC and CAM-ICU.
      Patients were followed-up until ICU discharge or for a maximum of 28 days.
      RESULTS: During the study period, 383 patients were admitted to the ICU and 162
      (42%) were evaluated; delirium was identified in 26.5% of patients by CAM-ICU and
      in 34.6% by ICDSC. There was agreement in diagnosing delirium diagnosis between
      the 2 methods in 42 (27.8%) patients and in excluding delirium in 105 (64.8%)
      patients. The ICDSC was positive in 14 (8.6%) patients in whom CAM-ICU was
      negative. Delirium, diagnosed either by ICDSC or CAM-ICU assessments, was
      associated with both significantly increased hospital LOS (14.8 +/- 8.3 vs 9.8 +/
      6.4, P < .001; 15.3 +/- 8.7 vs 10.5 +/- 7.1, P < .001, respectively), mortality
      in the ICU (11.1% vs 5.8%, P < .001; 12.5% vs 2.5%, P = .022), and in the
      hospital (10.7% vs 5.6%, P < .001; 23.2% vs 10.9%, P = .047). In addition,
      patients with positive ICDSC presenting with negative CAM-ICU had similar
      outcomes as compared with those without delirium. CONCLUSION: The findings of our
      study suggest that the CAM-ICU is better predictor of outcome when compared with
      ICDSC.

PMID- 21737238
TI  - Clinical profile, intensive care unit course, and outcome of patients admitted in
      intensive care unit with dengue.
AB  - PURPOSE: The purpose of the study was to assess the clinical profile and course
      of dengue patients admitted to the intensive care unit (ICU) and to identify
      factors related to poor outcome. METHODS: All patients with dengue admitted to
      ICU over 2.5 years were included prospectively. Severity of illness was assessed
      by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, and
      organ failure was determined by the Sequential Organ Failure Assessment score.
      Primary outcome measure was 28-day mortality. Logistic regression analysis was
      performed to identify factors predicting mortality. RESULTS: Data from 198
      patients were analyzed. Mean age was 39.56 +/- 17.1 years, and 61.1% were male.
      The commonest complaints were fever (96%) and rash (37.9%). Mean admission APACHE
      II and Sequential Organ Failure Assessment scores were 7.52 +/- 7.8 and 4.52 +/-
      3.4, respectively. The commonest organ failure was coagulation (43.4%) followed
      by respiratory failure (13.1%). Vasopressors were required by 11.6%; and dialysis
      and mechanical ventilation were required by 7.6% and 9.1%, respectively.
      Mortality was 12 (6.1%); and on multivariate analysis, APACHE II score (odds
      ratio, 1.781; 95% confidence interval, 0.967-3.281; P = .048) could independently
      predict mortality. CONCLUSIONS: Patients with dengue fever may require ICU
      admission for organ failure. Outcome is good if appropriate aggressive care and
      organ support are instituted. Admission APACHE II score may predict patients at
      higher risk of death.

PMID- 21737239
TI  - Pleural antigen assay in the diagnosis of pediatric pneumococcal empyema.
AB  - PURPOSE: The purpose of the study was to assess the diagnostic value of rapid
      pneumococcal antigen detection (PAD) in pleural fluid samples of children with
      empyema. MATERIAL AND METHODS: We performed a prospective evaluation in a
      pediatric intensive care unit of a tertiary university hospital of children aged
      1 month to 14 years admitted with empyema. Standard cultures (conventional
      microbiological culture [CMC]), PAD by immunochromatographic testing (Binax NOW
      Streptococcus pneumoniae; Binax, Portland, ME), and/or real-time polymerase chain
      reactions (RTPs) on pleural samples were performed in all included patients.
      RESULTS: Fifty-five cases with a mean (SD) age of 6.5 (6.1) years were enrolled.
      Streptococcus pneumoniae was identified in 28 cases (51%): by CMC in 15 cases and
      by RTP in a further 13 cases. Using CMC and/or RTP as the criterion standard, PAD
      showed a sensitivity of 96% (95% confidence interval, 86%-100%), a specificity of
      100% (75%-100%), a positive predictive value of 100% (98%-100%), and a Youden
      index of 0.96 (0.88-1.04). CONCLUSIONS: Pneumococcal antigen detection in pleural
      fluid specimens from children provides a rapid, simple, sensitive, and reliable
      method of diagnosis for pneumococcal empyema at bedside.

PMID- 21737240
TI  - Short-term prognosis of critically ill surgical patients: the impact of duration
      of invasive organ support therapies.
AB  - PURPOSE: We wanted to identify the importance of the duration of invasive
      ventilation and of renal replacement therapy for short-term prognosis of surgical
      patients treated in an intensive care unit (ICU). METHODS: We analyzed adult
      patients (n = 1462) who had an ICU length of stay of more than 4 days and who
      were followed up until the end of the short-term phase after ICU admission.
      Duration of different invasive therapies was evaluated by constructing specific
      vectors that tested effects of time-dependent variables on outcome after a lag
      time of 7 days. MEASUREMENTS AND MAIN RESULTS: Eight hundred eight patients
      (56.6%) were still alive at the end of the short-term phase. During the short
      term phase, 85.3% of the 1462 patients required invasive ventilation, and 16.1%,
      a continuous renal replacement therapy. Besides the underlying disease and
      disease severity at ICU admission, the need for invasive ventilation or renal
      replacement therapy was associated with poorer outcome. Duration of invasive
      ventilation shortened survival if treatment lasted for more than 11 days
      (nonlinear association). In contrast, duration of renal replacement therapy was
      unimportant for short-term prognosis. CONCLUSION: Prolonged duration of invasive
      ventilation but not of renal replacement therapy is inversely related to short
      term survival.

PMID- 21737241
TI  - Comparison of ventilator-associated pneumonia (VAP) rates between different ICUs:
      Implications of a zero VAP rate.
AB  - OBJECTIVE: Ventilator-associated pneumonia (VAP) is associated with significant
      morbidity and mortality. Measures to reduce the incidence of VAP have resulted in
      institutions reporting a zero or near-zero VAP rates. The implications of zero
      VAP rates are unclear. This study was done to compare outcomes between two
      intensive care units (ICU) with one of them reporting a zero VAP rate. DESIGN,
      SETTING AND PATIENTS: This study retrospectively compared VAP rates between two
      ICUs: Utah Valley Regional Medical Center (UVRMC) with 25 ICU beds and American
      Fork Hospital (AFH) with 9 ICU beds. Both facilities are under the same
      management and attended by a single group of intensivists. Both ICUs have similar
      nursing and respiratory staffing patterns. Both ICUs use the same intensive care
      program for reduction of VAP rates. ICU outcomes between AFH (reporting zero VAP
      rate) and UVRMC (VAP rate of 2.41/1000 ventilator days) were compared for the
      years 2007-2008. MEASUREMENTS AND MAIN RESULTS: UVRMC VAP rates during 2007 and
      2008 were 2.31/1000 ventilator days and 2.5/1000 ventilator days respectively
      compared to a zero VAP rate at AFH. The total days of ventilation, mean days of
      ventilation per patient and mean duration of ICU stay per patient was higher in
      the UVRMC group as compared to AFH ICU group. There was no significant difference
      in mean age and APACHE II score between ICU patients at UVRMC and AFH. There was
      no statistical difference in rates of VAP and mortality between UVRMC and AFH.
      CONCLUSIONS: During comparisons of VAP rate between institutions, a zero VAP rate
      needs to be considered in the context of overall ventilator days, mean durations
      of ventilator stay and ICU mortality.

PMID- 21737242
TI  - Cardiac manifestations in patients with pandemic (H1N1) 2009 virus infection
      needing intensive care.
AB  - PURPOSE: To characterize the cardiac manifestations in severe pandemic (H1N1)
      2009 virus [P(H1N1)2009v] infection. MATERIALS AND METHODS: Adult patients
      admitted to the intensive care unit were recruited. Patients with an elevated
      troponin I (>1.5 ng/mL) and those requiring vasoactive agents had an
      echocardiogram. Myocardial injury was defined as elevated troponin I. Patients
      with reduced ejection fraction lower than 50% were diagnosed as having left
      ventricular systolic dysfunction. Myocarditis was presumed when myocardial injury
      was associated with global myocardial dysfunction. Myocardial injury and
      dysfunction were correlated with mortality and expressed as odds ratio (OR) with
      95% confidence intervals (CI). RESULTS: Thirty-seven patients presented at 6.4
      (SD 3.2) days of illness. Four patients had valvular heart disease and 1
      preexisting ischemic heart disease. Seventeen (46%) patients had evidence of
      myocardial injury. Twenty of 28 patients in whom an echocardiogram was clinically
      indicated had left ventricular systolic dysfunction. Of these, 14 patients were
      diagnosed as having myocarditis, and most of them (12 patients) developed it
      early. Myocarditis was associated with longer duration of vasoactive agents (OR
      1.46, 95% CI 1.06-2.02) and mortality. Patients with elevated troponin I had an
      increased risk of death (OR 8.7, 95% CI 1.5-60). A higher mortality was observed
      in patients with left ventricular systolic dysfunction (OR 9.6, 95% CI 1.7-58)
      compared with those in whom an echocardiogram was normal or not indicated.
      CONCLUSION: In our cohort of severe P(H1N1)2009v infection, myocardial injury and
      dysfunction was frequent and associated with high mortality.

PMID- 21737243
TI  - Effect of attachment styles of individuals discharged from an intensive care unit
      on intensive care experience.
AB  - INTRODUCTION: The present study was conducted as a cross-sectional type to
      examine the effect of attachment styles of individuals discharged from an
      intensive care unit (ICU) on intensive care experience and health status.
      METHODS: The population of the study included patients discharged from the ICU in
      a university hospital. The sample included 108 patients who were selected via
      simple random sampling method. Data were collected using a Demographic
      Information Questionnaire, Intensive Care Experience Questionnaire, the
      Relationship Scales Questionnaire, and Acute Physiology and Chronic Health
      Evaluation II system. In the analysis of data, frequency, percentage, mean,
      standard deviation, minimum and maximum values, and Mann-Whitney U, Kruskal
      Wallis, Bonferroni-adjusted Mann-Whitney, and Spearman rho correlation tests were
      used. RESULTS: A significant difference in the awareness of surroundings subscale
      for attachment styles was noted (chi(2) = 10.820, P <= .01). Moreover,
      participants' attachment styles (fearful, preoccupied, and dismissing) and
      intensive care experience were significantly correlated. A significant
      correlation was found between participants' secure attachment style points and
      Acute Physiology and Chronic Health Evaluation II score during discharge from the
      ICU (r = 0.322, P = .001). CONCLUSION: Individuals' attachment styles should be
      taken into consideration when planning and implementing the nursing care and
      treatment of individuals hospitalized in an ICU.

PMID- 21737244
TI  - Device-associated infection rates and extra length of stay in an intensive care
      unit of a university hospital in Wroclaw, Poland: International Nosocomial
      Infection Control Consortium's (INICC) findings.
AB  - PURPOSE: The aim of this study was to determine device-associated health care
      associated infections (DA-HAI) rates, microbiologic profile, bacterial
      resistance, and length of stay in one intensive care unit (ICU) of a hospital
      member of the International Nosocomial Infection Control Consortium (INICC) in
      Poland. MATERIALS AND METHODS: A prospective DA-HAI surveillance study was
      conducted on an adult ICU from January 2007 to May 2010. Data were collected by
      implementing the methodology developed by INICC and applying the definitions of
      DA-HAI provided by the National Healthcare Safety Network at the US Centers for
      Disease Control and Prevention. RESULTS: A total of 847 patients hospitalized for
      9386 days acquired 206 DA-HAIs, an overall rate of 24.3% (95% confidence interval
      [CI], 21.5-27.4), and 21.9 (95% CI, 19.0-25.1) DA-HAIs per 1000 ICU-days. Central
      line-associated bloodstream infection rate was 4.01 (95% CI, 2.8-5.6) per 1000
      catheter-days, ventilator-associated pneumonia rate was 18.2 (95% CI, 15.5-21.6)
      per 1000 ventilator-days, and catheter-associated urinary tract infection rate
      was 4.8 (95% CI, 3.5-6.5) per 1000 catheter-days. Length of stay was 6.9 days for
      those patients without DA-HAI, 10.0 days for those with central line-associated
      bloodstream infection, 15.5 days for those with ventilator-associated pneumonia,
      and 15.0 for those with catheter-associated urinary tract infection. CONCLUSIONS:
      Most DA-HAI rates are lower in Poland than in INICC, but higher than in the
      National Healthcare Safety Network, expressing the feasibility of lowering
      infection rates and increasing patient safety.

PMID- 21737245
TI  - Acute Kidney Injury Network definition of contrast-induced nephropathy in the
      critically ill: incidence and outcome.
AB  - INTRODUCTION: Contrast-induced nephropathy (CIN) has been extensively studied in
      the ward but only scarcely in intensive care unit (ICU) patients, even if they
      may be particularly prone to develop or to worsen acute kidney insufficiency. We
      aimed to measure the incidence of CIN in a large ICU population using the Acute
      Kidney Injury Network (AKIN) definition and to investigate its impact on
      patients' outcome. METHODS: In this 3-year retrospective study, we included all
      patients undergoing, during their stay in our medical ICU, a contrast media
      enhanced computed tomographic scan. Change in serum creatinine between baseline
      (24 hours before to 12 hours after contrast media injection) and its maximum
      value over the 96 hours after contrast media injection was recorded. Contrast
      induced nephropathy was defined as a 44.2-MUmol/L absolute or a 25% relative
      minimal increase in serum creatinine over 48, 72, or 96 hours and according to
      the stage 1 of the AKIN classification (at least 26.4 MUmol/L or 50% increase
      over 48 hours). RESULTS: A total of 398 contrast-enhanced computed tomographic
      scans performed among 299 patients were analyzed. Incidence of CIN was 14%
      according to the AKIN definition and ranged from 8% (48-hour absolute definition)
      to 23% (96-hour relative definition). The need for renal replacement therapy and
      ICU mortality were significantly higher in case of CIN. After adjusting for other
      variables associated with ICU mortality, the occurrence of at least 1 CIN episode
      during the ICU stay (AKIN criteria) was independently associated with ICU
      mortality (odds ratio, 3.85; 95% confidence interval, 1.85-8.00). CONCLUSIONS:
      Even if incidence varied greatly depending on the definition, CIN appeared
      frequent in our critically ill patients. The AKIN definition, independently
      associated with ICU mortality, may allow unifying diagnostic criteria to further
      evaluate this condition that impacts morbidity and mortality.

PMID- 21737246
TI  - Vinpocetine inhibits glutamate release induced by the convulsive agent 4
      aminopyridine more potently than several antiepileptic drugs.
AB  - 4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases
      Glu, the most important excitatory amino acid neurotransmitter in the brain. Here
      the ionic dependence of 4-AP-induced Glu release and the effects of several of
      the most common antiepileptic drugs (AEDs) and of the new potential AED,
      vinpocetine on 4-AP-induced Glu release were characterized in hippocampus
      isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced
      [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+
      dependent fraction and a TTX insensitive fraction that was sensitive to the
      excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine,
      phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced
      [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective.
      Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu
      release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the
      direct blockade of presynaptic Na+ channels, may importantly contribute to the
      anticonvulsant actions of all the drugs tested here (except topiramate); and that
      the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu
      release when excitability is exacerbated like during seizures, may involve the
      increase additionally exerted by vinpocetine in some K+ channels permeability.

PMID- 21737247
TI  - The legacy of "just the facts".
AB  - This commentary to the capstone paper by Keshavan and colleagues reflects on the
      history of this project and the challenging nature of curating and establishing
      facts. While a number of approaches exist, none of them in-and-of-themselves are
      without drawbacks. A combination of techniques may provide the most satisfying
      results. We emphasize the importance of determining what facts are specific to
      the disorder - a particularly challenging endeavor - and the usefulness of
      various ways of quantifying these facts.

PMID- 21737248
TI  - Staphylococcus aureus in relation to physical, physiological and subjective
      conditions of apparently normal human skin.

PMID- 21737249
TI  - Analysis of resistance, cross-resistance and antimicrobial combinations for
      Pseudomonas aeruginosa isolates from 1997 to 2009.
AB  - Pseudomonas aeruginosa is a nosocomial and community-acquired pathogen associated
      with considerable patient morbidity and mortality. Multidrug resistance in P.
      aeruginosa is a concern owing to the limited therapeutic options available to
      treat infections due to this organism. In this study, rates of antimicrobial
      resistance of P. aeruginosa isolates collected by The Surveillance Network
      Database-USA (Eurofins Medinet, Chantilly, VA) from 1997 to 2009 were examined.
      The patient population and specimens were stratified according to patient setting
      and age as well as specimen source. Multidrug resistance was defined as
      resistance to three or more of the following antimicrobial agents: aztreonam;
      cefepime; ciprofloxacin; imipenem; gentamicin; and piperacillin/tazobactam (TZP).
      A total of 924740 P. aeruginosa isolates were examined in this study. Changes in
      resistance rates to individual antimicrobial agents were <5% for all agents
      except ciprofloxacin. There was a statistically significant decreasing rate of
      multidrug-resistant P. aeruginosa to four, five and six antimicrobial agents. For
      isolates resistant to imipenem, aztreonam and gentamicin, ciprofloxacin had the
      highest cross-resistance rates. The greatest coverage against P. aeruginosa was
      by the combination of TZP plus amikacin (94%) followed by aztreonam plus amikacin
      (90%). Pseudomonas aeruginosa resistance rates remained steady or minimally
      declined to all antimicrobials from 1997 to 2009. Amongst the beta-lactams, TZP
      has the greatest activity against P. aeruginosa.

PMID- 21737250
TI  - Metaorganisms as the new frontier.
AB  - Because it appears that almost all organisms are part of an interdependent
      metaorganism, an understanding of the underlying host-microbe species
      associations, and of evolution and molecular underpinnings, has become the new
      frontier in zoology. The availability of novel high-throughput sequencing
      methods, together with the conceptual understanding that advances mostly
      originate at the intersection of traditional disciplinary boundaries, enable
      biologists to dissect the mechanisms that control the interdependent associations
      of species. In this review article, we outline some of the issues in inter
      species interactions, present two case studies illuminating the necessity of
      interfacial research when addressing complex and fundamental zoological problems,
      and show that an interdisciplinary approach that seeks to understand co-evolved
      multi-species relationships will connect genomes, phenotypes, ecosystems and the
      evolutionary forces that have shaped them. We hope that this article inspires
      other collaborations of a similar nature on the diverse landscape commonly
      referred to as "zoology".

PMID- 21737251
TI  - Biotechnology for the acceleration of carbon dioxide capture and sequestration.
AB  - The potential for enzymatic acceleration of carbon dioxide capture from
      combustion products of fossil fuels has been demonstrated. Carbonic anhydrase
      (CA) accelerates post combustion CO(2) capture, but available CAs are woefully
      inadequate for the harsh conditions employed in most of these processes. In this
      review, we summarize recent approaches to improve CA, and processes employing
      this enzyme, to maximize the benefit from this extremely fast biocatalyst.
      Approaches to overcoming limitations include sourcing CAs from thermophilic
      organisms, using protein engineering to evolve thermo-tolerant enzymes,
      immobilizing the enzyme for stabilization and confinement to cooler regions and
      process modifications that minimize the (thermo-, solvent) stress on the enzyme.

PMID- 21737252
TI  - When brain clocks lose track of time: cause or consequence of neuropsychiatric
      disorders.
AB  - Patients suffering from neuropsychiatric disorders often exhibit a loss of
      regulation of their biological rhythms which leads to altered sleep/wake cycle,
      body temperature rhythm and hormonal rhythms. Whereas these symptoms have long
      been considered to result from the pathology of the underlying disease,
      increasing evidence now indicates that the circadian system may be more directly
      involved in the etiology of psychiatric disorders. This emerging view originated
      with the discovery that the genes involved in the generation of biological
      rhythms are expressed in many brain structures where clocks function-and perhaps
      malfunction. It is also due to the interesting phenotypes of clock mutant mice.
      Here we summarize recent reports showing that alteration of circadian clocks
      within key brain regions associated with neuropsychiatric disorders may be an
      underlying cause of the development of mental illness. We discuss how these
      alterations take place at both systems and molecular levels.

PMID- 21737253
TI  - Nutritional status at diagnosis is related to clinical outcomes in children and
      adolescents with cancer: a perspective from Central America.
AB  - BACKGROUND: The prevalence of malnutrition in children may exceed 50% in
      countries with limited resources. The aims of this study were to assess
      nutritional status at diagnosis in children and adolescents with cancer, and to
      correlate it with clinical outcomes in the Spanish speaking countries of Central
      America that formed the AHOPCA (Asociacion de Hemato-Oncologia Pediatrica de
      Centro America) consortium. METHODS: Patients aged 1-18 years, diagnosed with
      cancer between 1st October 2004 and 30th September 2007, were eligible for study.
      Weight (kg) and height or length (m), mid upper arm circumference--MUAC and
      triceps skin fold thickness--TSFT were measured and their Z-scores or percentiles
      were calculated. Three categories of nutritional status were defined according to
      these parameters. RESULTS: A total of 2954 new patients were enrolled; 1787 had
      all anthropometric measurements performed and 1513 also had measurements of serum
      albumin. By arm anthropometry 322/1787 patients (18%) had moderate nutritional
      depletion and 813/1787 patients (45%) were severely depleted. Adding serum
      albumin, the proportion classified as severely depleted rose to 59%. Malnourished
      children more often abandoned therapy and their event free survival was inferior
      to that of other children. CONCLUSIONS: Arm anthropometry in children with cancer
      is a sensitive measure of nutritional status. Since malnutrition at diagnosis was
      related to important clinical outcomes, an opportunity exists to devise simple,
      cost-effective nutritional interventions in such children that may enhance their
      prospects for survival.

PMID- 21737254
TI  - Survivors of childhood cancer lost to follow-up can be re-engaged into active
      long-term follow-up by a postal health questionnaire intervention.
AB  - Lifelong long-term follow-up (LTFU) is recommended for all survivors of childhood
      cancer. National guidelines recommend risk-stratified levels of follow-up by a
      multidisciplinary team, in an age-appropriate environment. Many survivors do not
      participate in long-term follow-up. OBJECTIVE: To re-engage childhood cancer
      survivors lost to follow-up in late effects programmes by means of postal
      questionnaire. POPULATION AND METHODS: Retrospective cohort study of all children
      (<19 years) diagnosed with cancer in a single institution in the UK between 1971
      and 2003. All lost to follow-up survivors (not seen in clinic >2 years) were sent
      a postal health and well-being questionnaire. RESULTS: 831 patients were
      diagnosed with childhood cancer between 1971 and 2003, with 575 long-term
      survivors (overall survival rate 69%). Information was available on 550 survivors
      (males 290 (53%), median age (range) at review 18.8 (5.4-44.2) years and at
      diagnosis 5.0 (0.0-18.8) years, and disease free survival (range) was 10.8 (1.0
      37.4) years. Of the 550 survivors, 256 (46%) were lost to follow-up. 99 (39%) of
      lost to follow-up survivors returned completed postal questionnaires (58%
      female). 45% of responders reported at least one late effect, 36% mild-moderate,
      and 8% severe-life threatening. 19% reported two or more late effects. 74% of all
      childhood cancer survivors are now in active follow-up. CONCLUSIONS: Almost half
      (46%) of all long-term survivors of childhood cancer are lost to follow-up,
      Postal follow-up is an effective means of re-engaging more than one third of
      survivors of childhood cancer in active long-term follow-up, half of whom had at
      least one late effect.

PMID- 21737255
TI  - Over-expression of SERPINB3 in hepatoblastoma: a possible insight into the
      genesis of this tumour?
AB  - BACKGROUND: The serpin SERPINB3 (SB3) found over-expressed in human
      hepatocellular carcinoma and in regenerating liver in mice has been shown to
      induce apoptosis resistance, epithelial-to-mesenchymal transition and increasing
      cellular invasion. It has also been hypothesised that SB3 may provide a pro
      proliferative stimulus for liver cells in vivo. No information is available on
      SB3 in hepatoblastoma (HB). Aims of the study were to analyse SB3 expression in
      HB specimens and to investigate its possible correlation with Myc expression and
      tumour extension at diagnosis as evaluated by the pre-treatment extent of disease
      evaluation system (PRETEXT). METHODS: Frozen tumour specimens from 42 children
      with HB were analysed for SB3 and Myc expression by real-time PCR. SB3
      localisation in tumour specimens was assessed by immunohistochemistry. RESULTS:
      At transcription level SB3 was positive in 79% of the cases. By
      immunohistochemistry, SB3 expression was found mainly in the embryonic,
      blastemal, small cell undifferentiated (SCUD) components of HB, while it was not
      detectable in normal hepatocytes. High SB3 reactivity was also detected in
      neoplastic cell clusters of portal vein tumour thrombosis. A direct correlation
      was observed between SB3 gene expression, the up-regulation of Myc (r=0.598,
      p<0.0001) and tumour extension (PRETEXT III/IV versus I/II, p=0.013).
      CONCLUSIONS: SB3 is over-expressed in HB and its expression is positively
      correlated with Myc expression and high tumour stage. The role of SB3 in the
      genesis of HB and in defining the risk profile of children affected by this
      tumour is hypothesised.

PMID- 21737256
TI  - Determining circulating endothelial cells using CellSearch system during
      preoperative systemic chemotherapy in breast cancer patients.
AB  - BACKGROUND: Circulating endothelial cells (CECs) have been studied as a biomarker
      for tumour progression and monitoring therapeutic effects. The CellSearch system
      is a semi-automated system that allows standardised analysis of CECs. This study
      assessed the clinical implications of CECs determined by the CellSearch system in
      breast cancer patients. METHODS: Seventy-six consecutive breast cancer patients
      (53 operable and 23 metastatic or recurrent) were enrolled for the study. Thirty
      five patients with operable breast cancer received preoperative chemotherapy with
      a regimen based on anthracycline and/or taxane. CECs are defined as
      CD146(+)CD105(+)CD45(-)DAPI(+) cells in the system. CD34 expression was examined
      using the additional channel in the system. RESULTS: A majority (4539 of 5183
      cells, 88%) of CECs from patients with operable breast cancer were CD34-positive.
      Triple-negative cancers showed higher baseline CEC and CD34(+)CEC counts than the
      other types (P=0.0387 and 0.0377, respectively). Low baseline CEC and CD34(+)CEC
      counts, and a low CD34 positive rate were associated with pathological complete
      response (pCR) of preoperative chemotherapy in patients with primary breast
      cancer (P=0.046, 0.027 and 0.01, respectively). In multivariate analyses, the
      CD34 positive rate was significant for pCR (P=0.021). During preoperative
      chemotherapy, CEC and CD34(+)CEC counts before each cycle of chemotherapy
      increased with taxane-based regimens (P=0.0018 and 0.0008, respectively) but not
      with anthracycline-based regimens. CONCLUSIONS: Baseline CEC, in particular
      CD34(+)CEC, counts and the CD34 positive rate might be useful for the prediction
      of treatment response of preoperative chemotherapy in patients with operable
      breast cancer.

PMID- 21737257
TI  - Meta-analysis confirms achieving pathological complete response after neoadjuvant
      chemotherapy predicts favourable prognosis for breast cancer patients.
AB  - Neoadjuvant chemotherapy (NAC) has become a widely accepted method of sequencing
      systemic therapy for breast cancer treatment. While 'response to chemotherapy' in
      the neoadjuvant setting has been utilised to predict prognosis, the published
      data are inconsistent. The present meta-analysis was conducted to determine
      whether the pathologic response to NAC predicts for outcomes. Papers were
      selected from the PubMed database based on defined inclusion and exclusion
      criteria. Parameters such as number/percentage of patients having pCR and outcome
      statistics (i.e. overall survival (OS), disease-free survival (DFS), relapse-free
      survival (RFS)) were collected. The analysis included 16 studies with 3776
      patients. The summary odds ratio (OR) estimating the association of OS with pCR
      was 3.44 (95% confidence interval [95%CI]: 2.45-4.84), with similar findings for
      DFS (OR=3.41, 95%CI: 2.54-4.58) and RFS (OR=2.45, 95%CI: 1.59-3.80). No obvious
      statistical heterogeneity was detected. Funnel plots and Egger's tests did not
      reveal publication bias. This meta-analysis confirms that pathologic response is
      a prognostic indicator for RFS, DFS and OS and suggests that patients achieving
      pCR after NAC have favourable outcomes.

PMID- 21737258
TI  - The use of a white rot fungi (Pleurotus ostreatus) immobilized on Amberlite XAD-4
      as a new biosorbent in trace metal determination.
AB  - The present work proposes the use of Pleurotus ostreatus immobilized on Amberlite
      XAD-4 as new biosorbent in trace metal determination. The effects of experimental
      parameters, such as "pH and flow rate of sample solution, amount of solid phase,
      eluent type, and concentration" on the recovery of the metal ions were
      investigated. Maximum adsorption of Cr(III), Cd(II) and Cu(II) ions took place in
      the pH range 4-5. These metal ions can be desorbed with 1M HCl (recovery 95
      100%). 0.2g adsorbent amount and 2.5 mL min(-1) flow rate was found to be optimum
      of all preconcentration experiments. The sorption capacity after 10 cycles of
      sorption and desorption does not vary more than 2.0%. The influences of the
      contaminant ions on the retentions of the analytes were also examined. The
      results showed that P. ostreatus immobilized on Amberlite XAD-4 can be considered
      as very promising material in trace metal determination.

PMID- 21737259
TI  - Comparison of microbially enhanced compost extracts produced from composted
      cattle rumen content material and from commercially available inocula.
AB  - A comparative study was performed on compost extracts prepared from cattle rumen
      content composted for three and nine months, nine month old compost inoculated
      with a Nutri-Life 4/20TM inoculum, and two commercial preparations (LivingSoilTM
      and Nutri-Life 4/20TM), all incubated for 48h. Nutri-Life 4/20TM had the highest
      concentrations of NO(3)(-)-N and K(+)-K, while rumen compost extract had higher
      humic and fulvic acids concentration. The bacterial and fungal community level
      functional diversity of three month old compost extract and of LivingSoilTM,
      assessed with BiologTM, were higher than that of nine month old rumen compost
      extract, with or without Nutri-Life 4/20TM inoculum, or Nutri-Life 4/20TM. No
      difference in fungal diversity was observed between treatments, as indicated by
      Denaturing Gradient Gel Electrophoresis (DGGE) analysis, however, bacterial
      diversity was higher in all compost extracts and LivingSoilTM compared to the
      Nutri-Life 4/20TM. Criteria for judging the quality of a microbially enhanced
      extract are discussed.

PMID- 21737260
TI  - Perspectives on cultivation strategies and photobioreactor designs for photo
      fermentative hydrogen production.
AB  - Photosynthetic bacteria have considerable biotechnological potential for
      biological hydrogen production due to higher substrate conversion efficiency and
      hydrogen yield. Phototrophic fermentation using photosynthetic bacteria has a
      major advantage of being able to further convert the byproducts originating from
      dark fermentation (e.g., volatile fatty acids) to hydrogen. Through the
      combination of dark and photo-fermentation processes, organic feedstock is fully
      converted into gaseous product (H2) at the highest possible H2 yield, with
      significant reduction of chemical oxygen demand (COD). The performance of photo
      fermentation is highly dependent on the medium composition, culture conditions,
      and photobioreactor design. Therefore, this article provides a critical review of
      the effects of key factors affecting the photo-hydrogen production efficiency of
      photosynthetic bacteria, and also summarizes the strategies being applied in
      promoting the performance of photo-fermentation.

PMID- 21737261
TI  - Co-firing of coal and manure biomass: a TG-MS approach.
AB  - Manure is a rich organic waste which, apart from its traditional use as a
      fertilizer, could be used as a bioenergy feedstock. In this sense, its
      utilization as a sole fuel or its co-combustion together with coal would be a
      choice for the management of this sort of biowaste. However, little is known
      about the behavior of this biowaste when submitted to high-temperature energy
      conversion processes. Thus, the separate combustion of swine manure and coal and
      their co-combustion (10% dried weight of manure) were studied by simultaneous
      TG/MS dynamic runs. TG-MS analysis was successfully used as an easy rapid tool to
      assess the combustion of manure, alone or together with coal. Furthermore, non
      isothermal kinetic analysis showed that the Arrhenius activation energy
      corresponding to the combustion of the blend (125.8-138.9 kJ/mol) was only
      slightly higher than that of manure (106.4-114.4 kJ/mol) or coal (107.0-119.6
      kJ/mol).

PMID- 21737262
TI  - Effect of lignocellulosic inhibitory compounds on growth and ethanol fermentation
      of newly-isolated thermotolerant Issatchenkia orientalis.
AB  - A newly isolated thermotolerant ethanologenic yeast strain, Issatchenkia
      orientalis IPE 100, was able to produce ethanol with a theoretical yield of 85%
      per g of glucose at 42 degrees C. Ethanol production was inhibited by furfural,
      hydroxymethylfurfural and vanillin concentrations above 5.56 gL(-1), 7.81 gL(-1),
      and 3.17 gL(-1), respectively, but the strain was able to produce ethanol from
      enzymatically hydrolyzed steam-exploded cornstalk with 93.8% of theoretical yield
      and 0.91 gL(-1)h(-1) of productivity at 42 degrees C. Therefore, I. orientalis
      IPE 100 is a potential candidate for commercial lignocelluloses-to-ethanol
      production.

PMID- 21737263
TI  - Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo-
      propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)
      carboxamide), a potent smoothened antagonist for use in Hedgehog pathway
      dependent malignancies, part 2.
AB  - The Hedgehog (Hh-) signaling pathway is a key developmental pathway which gets
      reactivated in many human tumors, and smoothened (Smo) antagonists are emerging
      as novel agents for the treatment of malignancies dependent on the Hh-pathway,
      with the most advanced compounds demonstrating encouraging results in initial
      clinical trials. A novel series of potent bicyclic hydantoin Smo antagonists was
      reported in the preceding article, these have been resolved, and optimized to
      identify potent homochiral derivatives with clean off-target profiles and good
      pharmacokinetic properties in preclinical species. While showing in vivo efficacy
      in mouse allograft models, unsubstituted bicyclic tetrahydroimidazo[1,5
      a]pyrazine-1,3(2H,5H)-diones were shown to epimerize in plasma. Alkylation of the
      C-8 position blocks this epimerization, resulting in the identification of MK
      5710 (47) which was selected for further development.

PMID- 21737264
TI  - Construction of a 19F-lectin biosensor for glycoprotein imaging by using affinity
      guided DMAP chemistry.
AB  - In this study, assisted by affinity-guided DMAP strategy, we developed a novel
      (19)F-modified lectin as a biosensor for specific detection and imaging of
      glycoproteins. Exploited the large chemical shift anisotropy property of (19)F
      nuclei, glycoproteins detected by our (19)F-biosensor are signatured by broadened
      peaks in (19)F NMR, hence enabled the distinction between glycoproteins and small
      molecule saccharides. Such signal on/off switching was also applied to
      glycoprotein imaging by (19)F MRI.

PMID- 21737265
TI  - Discovery and synthesis of a new class of opioid ligand having a 3
      azabicyclo[3.1.0]hexane core. An example of a 'magic methyl' giving a 35-fold
      improvement in binding.
AB  - In looking for a novel achiral MU opioid receptor antagonist for the treatment of
      pruritus, we designed and synthesised azabicyclo[3.1.0]hexane compounds as a new
      class of opioid ligand. During optimisation, an addition of a single methyl
      resulted in a 35-fold improvement in binding. An early example from the series
      had excellent MU opioid receptor antagonist antagonist activity and was very
      effective in an in vivo pruritus study.

PMID- 21737266
TI  - C-aryl glucosides substituted at the 4'-position as potent and selective renal
      sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors for the treatment of
      type 2 diabetes.
AB  - A series of C-aryl glucosides with various substituents at the 4'-position of the
      distal aryl ring have been synthesized and evaluated for inhibition of hSGLT1 and
      hSGLT2. Introduction of alkyl or alkoxy substituents at the 4'-position was found
      to improve SGLT2 potency, whereas introduction of a hydrophilic group at this
      position was deleterious. Compounds with alkoxy-, cycloalkoxy- or cycloalkenyloxy
      ethoxy scaffolds exhibited good inhibitory activity and high selectivity toward
      SGLT2. Selected compounds were investigated for in vivo efficacy.

PMID- 21737267
TI  - A facile synthesis of 1,5-disubstituted-2-aminoimidazoles: antibiotic activity of
      a first generation library.
AB  - An efficient synthetic route to 1,5-disubstituted 2-aminoimidazoles from readily
      available amino acids and aldehydes has been developed. A library of simple
      analogues was synthesized and several compounds were shown to exhibit notable
      antibiotic activity against a variety of bacterial strains including multi-drug
      resistant isolates.

PMID- 21737268
TI  - Flavans from Iris tenuifolia and their effects on beta-amyloid aggregation and
      neural stem cells proliferation in vitro.
AB  - Two new flavans (1, 2) and a new flavanone (3), together with three known
      compounds (4-6), were isolated from the roots of Iris tenuifolia. Their
      structures were elucidated by means of spectroscopic methods including 1D and 2D
      NMR techniques and mass spectrometry. Compounds 1, 4, and 6 were further
      confirmed by single-crystal X-ray diffraction analysis. Biological evaluation
      showed that compounds 1 and 4 were positive in inhibiting beta-amyloid (Abeta)
      aggregation and promoting neural stem cells (NSCs) proliferation, respectively.

PMID- 21737269
TI  - The novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of N-aryl urea:
      synthesis, anti-inflammatory, antibacterial and antifungal activity evaluation.
AB  - A series of novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of biological
      interest were prepared by sequential Bigineli's reaction, reduction followed by
      reaction of resulting amines with different arylisocynates. All the synthesized
      (1-23) compounds were screened against the pro-inflammatory cytokines (TNF-alpha
      and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological
      activity evaluation study reveled that among all the compounds screened,
      compounds 12 and 17 found to have promising anti-inflammatory activity (68-62%
      TNF-alpha and 92-86% IL-6 inhibitory activity at 10 MUM). Interestingly compounds
      3, 4, 5, 6, 15, 22 and 23 revealed promising antimicrobial activity at MIC of 10
      30 MUg/mL against selected pathogenic bacteria and fungi.

PMID- 21737270
TI  - New C-23 modified of silybin and 2,3-dehydrosilybin: synthesis and preliminary
      evaluation of antioxidant properties.
AB  - Silybin is the major flavonolignan of silymarin and it displays a plethora of
      biological effects, generally ascribed to its antioxidant properties. Herein we
      shall describe an efficient synthetic strategy to obtain a variety of new and
      more water-soluble silybin and 2,3-dehydrosilybin (DHS) derivatives in which the
      23-hydroxyl group was converted to a sulfate, phosphodiester, or amine group,
      using a solution-phase approach. Furthermore a new and efficient method for the
      preparation of DHS from silybin was developed and optimised. The antioxidant
      properties of the new compounds were evaluated in a cellular model in vivo and
      they displayed an antioxidant activity comparable to or higher than silybin and
      DHS, being able to prevent H(2)O(2)-induced generation of intracellular reactive
      oxygen species (ROS). Most of the derivatives also displayed a better
      hydrophilicity while retaining the biological activities of silybin and they
      might broaden the in vivo applications of this class of natural compounds.

PMID- 21737271
TI  - New isoprenylated flavonoids and adipogenesis-promoting constituents from Morus
      notabilis.
AB  - Five new isoprenylated flavonoids, notabilisins A-E (1-5), and two known Diels
      Alder adducts (6 and 7), were isolated from the twigs of Morus notabilis.
      Compounds 4 and 5 possess two novel pyran rings, which may be biogenetically
      derived from 3. Compounds 1 and 3 significantly promoted adipogenesis,
      characterized by increased lipid droplet and triglyceride content in 3T3L1 cells,
      and induced up-regulation of the expression of adipocyte-specific genes, aP2 and
      GLUT4.

PMID- 21737272
TI  - Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2
      phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimid azo[1,5-a]pyrazine
      7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway
      dependent malignancies, part 1.
AB  - The Hedgehog (Hh-) signaling pathway is a key developmental pathway which
      controls patterning, growth and cell migration in most tissues, but evidence has
      accumulated showing that many human tumors aberrantly reactivate this pathway.
      Smoothened antagonists offer opportunities for the treatment of malignancies
      dependent on the Hh pathway, and the most advanced clinical candidates are
      demonstrating encourage initial results. A novel series of [6,5]-bicyclic
      tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione smoothened antagonists has been
      identified, and the series has been extensively explored to ascertain the key
      detriments for activity, demonstrating that the trans-2-phenylcyclopropyl and
      hydantoin ring systems are critical for potency, while a variety of urea
      substituents can be tolerated. The combination of these optimal groups gives
      smoothened antagonists with activity in the low nanomolar range.

PMID- 21737273
TI  - Synthesis, in vitro evaluation and molecular docking studies of new triazole
      derivatives as antifungal agents.
AB  - On the basis of the active site of lanosterol 14alpha-demethylase from Candida
      albicans (CACYP51), a series of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4
      triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one derivatives were synthesized as
      fluconazole analogs. Results of the preliminary antifungal tests against eight
      human pathogenic fungi in vitro showed that these compounds exhibited activities
      to some extent, and some displayed excellent antifungal activities against C.
      albicans than reference drug fluconazole. Flexible molecular docking was used to
      analyze the structure-activity relationships (SARs) of the target compounds. The
      designed compounds interact with CACYP51 through hydrophobic, van der Waals and
      hydrogen-bonding interactions.

PMID- 21737274
TI  - Synthesis, molecular modeling and bio-evaluation of cycloalkyl fused 2
      aminopyrimidines as antitubercular and antidiabetic agents.
AB  - An economical and efficient one step synthesis of a series of 8-(arylidene)-4
      (aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)
      6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis
      benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has
      been developed. All the synthesized compounds were evaluated against
      Mycobacterium tuberculosis H(37)Rv strain and the alpha-glucosidase and glycogen
      phosphorylase enzymes. Few of the compounds have shown interesting in vitro
      activity with MIC up to 3.12 MUg/mL against M. tuberculosis and very good
      inhibition of alpha-glucosidase and glycogen phosphorylase enzymes. The most
      potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12
      MUg/mL. The present study opens a new gate to synthesize antitubercular agents
      for diabetic TB patients. In silico docking studies indicate that mycobacterial
      dihydrofolate reductase is the possible target of these compounds.

PMID- 21737275
TI  - Enhancing translation: guidelines for standard pre-clinical experiments in mdx
      mice.
AB  - Duchenne Muscular Dystrophy is an X-linked disorder that affects boys and leads
      to muscle wasting and death due to cardiac involvement and respiratory
      complications. The cause is the absence of dystrophin, a large structural protein
      indispensable for muscle cell function and viability. The mdx mouse has become
      the standard animal model for pre-clinical evaluation of potential therapeutic
      treatments. Recent years have seen a rapid increase in the number of experimental
      compounds being evaluated in the mdx mouse. There is, however, much variability
      in the design of these pre-clinical experimental studies. This has made it
      difficult to interpret and compare published data from different laboratories and
      to evaluate the potential of a treatment for application to patients. The authors
      therefore propose the introduction of a standard study design for the mdx mouse
      model. Several aspects, including animal care, sampling times and choice of
      tissues, as well as recommended endpoints and methodologies are addressed and,
      for each aspect, a standard procedure is proposed. Testing of all new
      molecules/drugs using a widely accepted and agreed upon standard experimental
      protocol would greatly improve the power of pre-clinical experimentations and
      help identifying promising therapies for the translation into clinical trials for
      boys with Duchenne Muscular Dystrophy.

PMID- 21737276
TI  - Rapid evolutionary rewiring of a structurally constrained eye enhancer.
AB  - BACKGROUND: Enhancers are genomic cis-regulatory sequences that integrate
      spatiotemporal signals to control gene expression. Enhancer activity depends on
      the combination of bound transcription factors as well as-in some cases-the
      arrangement and spacing of binding sites for these factors. Here, we examine
      evolutionary changes to the sequence and structure of sparkling, a
      Notch/EGFR/Runx-regulated enhancer that activates the dPax2 gene in cone cells of
      the developing Drosophila eye. RESULTS: Despite functional and structural
      constraints on its sequence, sparkling has undergone major reorganization in its
      recent evolutionary history. Our data suggest that the relative strengths of the
      various regulatory inputs into sparkling change rapidly over evolutionary time,
      such that reduced input from some factors is compensated by increased input from
      different regulators. These gains and losses are at least partly responsible for
      the changes in enhancer structure that we observe. Furthermore, stereotypical
      spatial relationships between certain binding sites ("grammar elements") can be
      identified in all sparkling orthologs-although the sites themselves are often
      recently derived. We also find that low binding affinity for the Notch-regulated
      transcription factor Su(H), a conserved property of sparkling, is required to
      prevent ectopic responses to Notch in noncone cells. CONCLUSIONS: Rapid DNA
      sequence turnover does not imply either the absence of critical cis-regulatory
      information or the absence of structural rules. Our findings demonstrate that
      even a severely constrained cis-regulatory sequence can be significantly rewired
      over a short evolutionary timescale.

PMID- 21737277
TI  - FLOWERING LOCUS T regulates stomatal opening.
AB  - Stomatal pores surrounded by a pair of guard cells in the plant epidermis control
      gas exchange for photosynthesis in response to light, CO(2), and phytohormone
      abscisic acid. Phototropins (phot1 and phot2) are plant blue-light receptor
      kinases and mediate stomatal opening via activation of the plasma membrane H(+)
      ATPase. However, the signaling mechanism from phototropins to the H(+)-ATPase has
      yet to be determined. Here, we show that FLOWERING LOCUS T (FT) is expressed in
      guard cells and regulates stomatal opening. We isolated an scs (suppressor of
      closed-stomata phenotype in phot1 phot2) 1-1 mutant of Arabidopsis thaliana and
      showed that scs1-1 carries a novel null early flowering 3 (elf3) allele in a
      phot1 phot2 background. scs1-1 (elf3 phot1 phot2 triple mutant) had an open
      stomata phenotype with high H(+)-ATPase activity and showed increased levels of
      FT mRNA in guard cells. Transgenic plants overexpressing FT in guard cells showed
      open stomata, whereas a loss-of-function FT allele, ft-1, exhibited closed
      stomata and failed to activate the H(+)-ATPase in response to blue light. Our
      results define a new cell-autonomous role for FT and demonstrate that the
      flowering time genes ELF3 and FT are involved in the regulation of H(+)-ATPase by
      blue light in guard cells.

PMID- 21737278
TI  - Notch-dependent induction of left/right asymmetry in C. elegans interneurons and
      motoneurons.
AB  - Although nervous systems are largely bilaterally symmetric on a structural level,
      they display striking degrees of functional left/right (L/R) asymmetry. In
      Caenorhabditis elegans, two structurally symmetric pairs of sensory neurons, ASE
      and AWC, display two distinctly controlled types of functional L/R asymmetries
      (stereotyped versus stochastic asymmetry). Beyond these two cases, the extent of
      neuronal asymmetry in the C. elegans nervous system was unclear. Here, we report
      that the Beta3/Olig-type bHLH transcription factor hlh-16 is L/R asymmetrically
      expressed in several distinct, otherwise bilaterally symmetric interneuron and
      motoneuron pairs that are part of a known navigation circuit. We find that hlh-16
      asymmetry is generated during gastrulation by an asymmetric LAG-2/Delta signal
      originating from the mesoderm that promotes hlh-16 expression in neurons on the
      left side through direct binding of the Notch effector LAG-1/Su(H)/CBF to a cis
      regulatory element in the hlh-16 locus. Removal of hlh-16 reveals an
      unanticipated asymmetry in the ability of the axons of the AIY interneurons to
      extend into the nerve ring, with the left AIY axon requiring elevated hlh-16
      expression for correct extension. Our study suggests that the extent of molecular
      L/R asymmetry in the C. elegans nervous system is broader than previously
      anticipated, establishes a novel signaling mechanism that crosses germ layers to
      diversify bilaterally symmetric neuronal lineages, and reveals L/R asymmetric
      control of axonal outgrowth of bilaterally symmetric neurons.

PMID- 21737279
TI  - The same regulatory point mutation changed seed-dispersal structures in evolution
      and domestication.
AB  - It is unclear whether gene regulatory changes that drive evolution at the
      population and species levels [1-3] can be extrapolated to higher taxonomic
      levels. Here, we investigated the role of cis-regulatory changes in fruit
      evolution within the Brassicaceae family. REPLUMLESS (RPL, At5g02030) controls
      development of the replum, a structure with an important role in fruit opening
      and seed dispersal [6]. We show that reduced repla resembling the Arabidopsis rpl
      mutant correlated across the Brassicaceae with a point mutation in a conserved
      cis-element of RPL. When introduced in Arabidopsis, this nucleotide change
      specifically reduced RPL expression and function in the fruit. Conversely,
      Brassica RPL containing the Arabidopsis version of the cis-element was sufficient
      to convert the Brassica replum to an Arabidopsis-like morphology. A mutation in
      the same nucleotide position of the same cis-element in a RPL ortholog has been
      independently selected to reduce seed dispersal during domestication of rice, in
      spite of its very different fruit anatomy. Thus, single-nucleotide regulatory
      mutations at the same position explain developmental variation in seed-dispersal
      structures at the population and family levels and suggest that the same genetic
      toolkit is relevant to domestication and natural evolution in widely diverged
      species.

PMID- 21737280
TI  - Ancient hybridization and an Irish origin for the modern polar bear matriline.
AB  - BACKGROUND: Polar bears (Ursus maritimus) are among those species most
      susceptible to the rapidly changing arctic climate, and their survival is of
      global concern. Despite this, little is known about polar bear species history.
      Future conservation strategies would significantly benefit from an understanding
      of basic evolutionary information, such as the timing and conditions of their
      initial divergence from brown bears (U. arctos) or their response to previous
      environmental change. RESULTS: We used a spatially explicit phylogeographic model
      to estimate the dynamics of 242 brown bear and polar bear matrilines sampled
      throughout the last 120,000 years and across their present and past geographic
      ranges. Our results show that the present distribution of these matrilines was
      shaped by a combination of regional stability and rapid, long-distance dispersal
      from ice-age refugia. In addition, hybridization between polar bears and brown
      bears may have occurred multiple times throughout the Late Pleistocene.
      CONCLUSIONS: The reconstructed matrilineal history of brown and polar bears has
      two striking features. First, it is punctuated by dramatic and discrete climate
      driven dispersal events. Second, opportunistic mating between these two species
      as their ranges overlapped has left a strong genetic imprint. In particular, a
      likely genetic exchange with extinct Irish brown bears forms the origin of the
      modern polar bear matriline. This suggests that interspecific hybridization not
      only may be more common than previously considered but may be a mechanism by
      which species deal with marginal habitats during periods of environmental
      deterioration.

PMID- 21737281
TI  - Calculation of plantar pressure time integral, an alternative approach.
AB  - In plantar pressure measurement, both peak pressure and pressure time integral
      are used as variables to assess plantar loading. However, pressure time integral
      shows a high concordance with peak pressure. Many researchers and clinicians use
      Novel software (Novel GmbH Inc., Munich, Germany) that calculates this variable
      as the summation of the products of peak pressure and duration per time sample,
      which is not a genuine integral of pressure over time. Therefore, an alternative
      calculation method was introduced. The aim of this study was to explore the
      relevance of this alternative method, in different populations. Plantar pressure
      variables were measured in 76 people with diabetic polyneuropathy, 33 diabetic
      controls without polyneuropathy and 19 healthy subjects. Peak pressure and
      pressure time integral were obtained using Novel software. The quotient of the
      genuine force time integral over contact area was obtained as the alternative
      pressure time integral calculation. This new alternative method correlated less
      with peak pressure than the pressure time integral as calculated by Novel. The
      two methods differed significantly and these differences varied between the foot
      sole areas and between groups. The largest differences were found under the
      metatarsal heads in the group with diabetic polyneuropathy. From a theoretical
      perspective, the alternative approach provides a more valid calculation of the
      pressure time integral. In addition, this study showed that the alternative
      calculation is of added value, along peak pressure calculation, to interpret
      adapted plantar pressures patterns in particular in patients at risk for foot
      ulceration.

PMID- 21737282
TI  - Transient global amnesia during a professional cello concert.
AB  - Transient global amnesia (TGA) is a great curiosity in medicine, the underlying
      pathophysiology of which remains under debate. When an episode occurs during the
      performance of a task requiring refined technical skills and an intense level of
      concentration such as a musical performance, it draws attention to the
      relationship between memory and performance. It also raises questions of access
      to procedural memory and other aspects of stored information. We encountered a
      renowned and highly proficient musician who was amnestic for a challenging
      concert.

PMID- 21737283
TI  - Susceptible gene single nucleotide polymorphism and hemorrhage risk in patients
      with brain arteriovenous malformation.
AB  - The relationship between single nucleotide polymorphism (SNP) of interleukin-17
      (IL-17A), transforming growth factor beta (TGF-beta), as well as its receptor
      (TGFR-beta2) and susceptibility to intracerebral hemorrhage in patients with
      brain arteriovenous malformation (BAVM) was investigated in the present study. A
      total of 53 patients with BAVM and 120 healthy controls were recruited, all of
      whom were Han Chinese from South China. There were no statistically significant
      differences in the IL-17A-197 guanine/adenine (G/A) or TGF-beta1-509
      cytosine/thymine (C/T) genotypes or gene frequencies between BAVM patients and
      controls (p>0.05), but the gene frequency of the TGFR-beta2-875 A/G genotype in
      patients with BAVM was significantly higher (p<0.05). Furthermore, the
      frequencies of the G allele of IL-17A-197 G/A and TGFR-beta2-875 A/G in BAVM
      patients with hemorrhage were higher than those without hemorrhage. TGFR-beta2
      875 G/G genotype is a risk factor for BAVM, and the IL-17A-197 G/A and TGFR-beta2
      875 A/G genotype is closely related to hemorrhage risk for patients with BAVM.

PMID- 21737284
TI  - Gliosarcoma arising from a fibrillary astrocytoma.
AB  - We report a 67-year-old woman who was diagnosed with a gliosarcoma at a second
      operation after diagnosis of a fibrillary astrocytoma 5 months previously.
      Initially, she underwent a CT-guided stereotactic biopsy. Histological
      examination showed fibrillary astrocytoma (World Health Organization [WHO] grade
      II). Loss of heterozygosity (LOH) on 1p, 10q, and 19q was not detected. She
      received chemotherapy, but no radiotherapy. Five months after the biopsy, MRI
      revealed rapid tumor growth. Tissue obtained from partial removal of the tumor
      revealed gliosarcoma (WHO grade IV), and LOH on 10q and 19q was detected. The
      history, histopathology, and genetic alterations of this patient are discussed.

PMID- 21737285
TI  - Discovery of selective indole-based prostaglandin D2 receptor antagonist.
AB  - A series of N-benzoyl-2-methylindole-3-acetic acids were synthesized and
      biologically evaluated as prostaglandin (PG) D2 receptor antagonists. Some of the
      selected compounds significantly inhibited OVA-induced vascular permeability in
      guinea pig conjunctiva after oral dosing. Structure-activity relationship study
      is presented.

PMID- 21737286
TI  - Palmerolide macrolides from the Antarctic tunicate Synoicum adareanum.
AB  - Palmerolides D-G are new bioactive macrolides isolated from the Antarctic
      tunicate Synoicum adareanum and are related to the melanoma-selective cytotoxin
      palmerolide A. Most of these palmerolides are potent V-ATPase inhibitors and have
      sub-micromolar activity against melanoma. Though palmerolide A remains the most
      potent of this series of natural products against mammalian V-ATPase, recent data
      suggests that palmerolide D is the most potent against melanoma. A comparison of
      the bioactivity data obtained for these natural product palmerolides has provided
      insight into the substructures necessary to retain V-ATPase inhibition and
      cytotoxic activity.

PMID- 21737287
TI  - Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as
      a PET tracer for type 2 cannabinoid receptor imaging.
AB  - The type 2 cannabinoid receptor (CB2R) is part of the endocannabinoid system and
      is expressed in tissues related to the immune system. As the CB2R has a very low
      brain expression in non-pathological conditions, but is upregulated in activated
      microglia, it is an interesting target for visualization of neuroinflammation
      using positron emission tomography with a suitable radiolabeled CB2R ligand. In
      this study, we radiolabelled a fluoroethyl derivative of GW405833, a well known
      CB2R partial agonist, with fluorine-18 (half-life 109.8 min) by alkylation of the
      phenol precursor with 1-bromo-2-[18F]fluoroethane. In vitro studies showed that
      FE-GW405833 behaved as a selective high affinity (27 nM) inverse agonist for
      hCB2R. [18F]FE-GW405833 showed moderate initial brain uptake in mice and rats,
      but a slow washout from brain and plasma due to retention of a radiometabolite.
      Specific binding of the tracer to human CB2R was demonstrated in vivo in a rat
      model with local CB2R overexpression in the brain. Optimized derivatives of
      GW405833 that are less susceptible to metabolism will need to be developed in
      order to provide a useful tracer for CB2R quantification with PET.

PMID- 21737288
TI  - Synthesis and biological evaluation of 4beta-acrylamidopodophyllotoxin congeners
      as DNA damaging agents.
AB  - A series of new 4beta-acrylamidopodophyllotoxin derivatives (13a-o) were
      synthesized by coupling of substituted acrylic acids (10a-l and 11m-o) to the
      4beta-aminopodophyllotoxin. The synthesized derivatives 13a-o were evaluated for
      their cytotoxicity against five human cancer cell lines (breast, oral, colon,
      lung and ovarian). These podophyllotoxin conjugates have shown promising activity
      with GI50 values ranging from <0.1 to 0.29 MUM. Some of the compounds 13j, 13k
      and 13l that showed significant antiproliferative activity were also evaluated
      for related cytotoxic effects in MCF-7 cells, and compared to etoposide. These
      compounds (13j, 13k and 13l) showed G2/M cell cycle arrest and the apoptotic
      event was found to be due to both the single-strand DNA breaks as observed by
      comet assay as well as double-strand breaks as observed by the large accumulation
      of gamma H2AX foci.

PMID- 21737289
TI  - Bone regeneration with BMP-2 and hydroxyapatite in critical-size calvarial
      defects in rats.
AB  - BACKGROUND: This study describes the effect of bone formation by BMP-2 (bone
      morphogenetic protein-2), a bone formation inducer, with or without
      hydroxyapatite (HAP) application to critical-size defects in rat calvarial bone.
      MATERIAL AND METHODS: Twenty male Wistar rats were divided into four groups of 5
      animals each: control, HAP, BMP, and mixed BMP/HAP. A Critical-size defect of 4mm
      was made using a trephine in the calvarial bone and, after that, BMP and/or HAP
      was applied to the defect according to the grouping. Defects were evaluated
      radiographically and histologically using ImageJ color analyzer software at 4
      weeks postoperatively. RESULTS: The histological data were more precise than the
      radiologic data due to the white color of the porous-type HAP material. The
      highest radiopacity was noted in the mixed BMP/HAP group (162.07+/-9.06),
      followed by the HAP group (133.15+/-21.8), then the BMP group (100.79+/-8.27),
      and, lastly, the control group (54.45+/-8.39). After subtracting the white
      background and using ImageJ for histological analysis, the highest rate of
      osteochondrogenesis was in the mixed BMP/HAP group (85.29%+/-8.21), and then the
      BMP group (77.34%+/-7.39), followed by the HAP group (59.82%+/-11.23), and,
      lastly, the control group (40.27%+/-7.44). Differences in the values between
      groups were then analyzed using confidence intervals (CI) of 95 and 99%.
      CONCLUSION: Within 4 weeks, the mixed BMP/HAP group showed the highest level of
      bone induction, especially compared to the BMP group, but this was non
      significant; even with a 95% CI, the result was negative. This reveals that BMP
      alone can be applied, with a final result the same as that seen in the mixed
      BMP/HAP group. BMP and HAP, both being osteoinducting agents, even though they
      differ from a material classification point of view, have a positive effect on
      osteogenesis.

PMID- 21737290
TI  - Melanotic neuroectodermal tumour of infancy: report of two cases and review of
      the literature.
AB  - Melanotic neuroectodermal tumour of infancy (MNTI) is an uncommon tumour
      affecting predominantly the craniofacial bones of the newborn infants. The neural
      crest origin of the tumour has been confirmed. MNTI is generally accepted as a
      benign tumour despite of its rapid and locally infiltrative growth. Recurrence
      rate varies between 10% and 60%, and malignant behaviour has been reported in
      6.5% of MNTIs. Systematic review of the literature revealed 445 MNTIs published
      between 1918 and 2010. We present additional two cases of MNTI from our
      Department, typical in all terms, which equals a total number of 447 reported
      cases. One of our cases revealed histological features consistent with malignant
      behaviour, but at present, 18 months after the surgical excision, there is no
      evidence of recurrence. Biological behaviour of MNTI cannot be predicted by gross
      or histologic characteristics, thus early diagnosis and careful follow-up after
      the complete surgical excision is required.

PMID- 21737291
TI  - An unusual presentation of a usual cardiac mass: neo-vascularised left-atrial
      myxoma.

PMID- 21737292
TI  - A novel approach to percutaneous right-ventricular mechanical support.
AB  - OBJECTIVE: We report our initial experience with our newly developed percutaneous
      right-ventricular assist device (VAD) with CentriMag (perc CM-RVAD). METHODS: A
      flexible outflow cannula placed from the right internal jugular vein to the
      pulmonary artery and an inflow cannula placed from the femoral vein to the right
      atrium constituted the perc CM-RVAD. When needed, biventricular support was
      provided with left VAD (LVAD), either with a percutaneous LVAD placed through
      axillary or femoral artery access or with a fully implantable LVAD. RESULTS:
      Between January 2009 and June 2010, all of the attempted patients successfully
      received perc CM-RVAD (n = 8). Mean blood pressure, heart rate, and central
      venous pressure showed a trend toward improvement after the perc CM-RVAD, with
      less inotrope/vasopressor requirement. Mixed venous oxygen saturation (SvO(2))
      increased significantly from 64 +/- 20 Torr to 78 +/- 6 Torr (P < 0.01). The
      percutaneous VADs were explanted after myocardial recovery in seven patients;
      however, in three of these, perc CM-RVAD was used as a temporary bridge to other
      devices. One patient was bridged to a surgical biventricular assist device
      (BiVAD) and transferred back to the referring hospital on support. One death
      occurred due to multiple-organ failure 8 days after explantation of the RVAD with
      recovery. CONCLUSIONS: Perc CM-RVAD was feasible and provided hemodynamic
      improvement.

PMID- 21737293
TI  - Intra-operative device closure of multiple atrial septal defects facilitated by a
      unique atrial septum remodeling technique: initial results and experience in 11
      patients.
AB  - OBJECTIVE: We introduced a new atrial septum remodeling technique and further
      investigated the feasibility of this method in facilitating the intra-operative
      device closure (IODC) of multiple atrial septal defects (ASDs). METHODS: Adult
      patients with multiple nearby ASDs, which were not eligible for transcatheter
      closure, were enrolled in this study. Transesophageal echocardiogram (TEE) was
      applied for intra-operative evaluation. The multiple ASDs were divided into three
      different types according to its morphology. Based on the concept of breaking the
      rim between multiple ASDs and making it feasible for single device closure,
      atrial septum remodeling procedure was carried out via pre-atrial approach using
      special clamp under the guidance of TEE. IODC was then attempted for reshaped
      ASD. Successful rate and perioperative complications were then noted. RESULTS:
      Eleven patients were enrolled in this study, with mean age being 23.4 +/- 5.3
      years and mean weight 51.6 +/- 8.0 kg. Among them, seven patients have double
      ASDs and four have triple ASDs. Mean diameter of isolated ASD was 10.4 +/- 3.8 mm
      with a mean distance of 3.2 +/- 1.2 mm between each other. Atrial septum
      remodeling procedure was successfully done in all patients. One device was then
      used for each patient. Mean ASD diameter after remodeling procedure was 20.6 +/-
      3.9 mm with mean device size 23.5 +/- 4.0 mm. Complete closure of multiple ASDs
      was achieved in nine patients immediately after the procedure; two patients had
      trivial grade shunt after device deployment that resolved within the 3-month
      follow-up. No severe complications were noticed during the perioperative period
      and the 3-month follow-up. CONCLUSIONS: Atrial septum remodeling technique seems
      to be a safe and effective method that could largely facilitate the successful
      IODC of multiple ASDs.

PMID- 21737294
TI  - Phenotypic spectrum and management of sternal cleft: literature review and
      presentation of a new series.
AB  - Sternal cleft is a chest wall malformation that can expose mediastinal viscera
      and vessels to injuries. It can be classified into two forms, complete and
      partial. Its etiology and incidence are unknown and it is often associated with
      other defects. The aim of this article is to review the literature and report our
      experience with this rare anomaly, focusing on clinical presentation and
      management. We reviewed the English written literature about sternal cleft and
      collected the clinical data of all the published series. We present seven new
      cases that we have observed and treated since 1999. Literature reports 51 series
      including 86 patients, more frequently female (62%) and affected with partial
      superior form (67%). Sternal cleft is often asymptomatic (74%) and associated
      with other defects (72%). Surgical treatments include primary closure (73%), bone
      graft interposition (10%), prosthetic closure (7%), and muscle flap interposition
      (3%). In our series, primary closure was possible in four cases, while in three
      cases we placed a prosthesis. Five patients had associated defects and two were
      affected with PHACES (posterior fossa abnormalities, hemangiomas, arterial
      lesions, cardiac abnormalities/aortic coarctation, abnormalities of the eye, and
      sternum defects) syndrome. We report for the first time the association of
      sternal cleft with connectival nevi in three of our patients. At follow-up, we
      observed no major complication or recurrences. Although primary closure is the
      preferred option and should be performed in the neonatal period, the use of
      prostheses warrants good results as well. Prior to treatment, associated defects
      and syndromes should be excluded.

PMID- 21737295
TI  - Adenosquamous carcinoma of the lung: surgical results as compared with squamous
      cell and adenocarcinoma cases.
AB  - OBJECTIVES: An adenosquamous carcinoma (ASC) of the lung is a relatively rare
      tumor. In this multi-institutional cohort study, we tested the hypothesis that an
      ASC exhibits more aggressive clinical behavior as compared to adenocarcinoma (AC)
      and squamous cell carcinoma (SC). METHODS: This retrospective cohort study used a
      prospective database produced by the Japan National Hospital Organization Study
      Group for Lung Cancer over a 7-year period (operations from 1997 to 2003, follow
      up data until March 2010). During that period, 4668 cases underwent an operation
      for various types of primary malignant lung tumors. When a sample from a tumor
      comprised at least 20% each of SC and AC, the case was classified as ASC.
      Pathologic staging was done according to the seventh edition of the International
      Union against Cancer (UICC) Tumor Node Matastasis (TNM) classification of
      malignant tumors. RESULTS: We identified 114 patients with ASC (2.4%), 2993 with
      AC (64.2%), and 1369 with SC (29.3%). Kaplan-Meier survival curves for all stage
      cases, p-stage IA, IB, and IIIA tumors indicated that ASC cases had the least
      favorable survival. The 5-year survival rates for all stage cases were 23.3% for
      ASC, 58.0% for AC (p < 0.0001), and 40.8% for SC (p < 0.0001). The 5-year
      survival rates for p-stage IA were 42.0% for ASC, 81.8% for AC (p = 0.0005), and
      63.4% for SC not significant (NS), while those for p-stage IB were 19.3%, 65.3%
      (p = 0.0024), and 46.8% (NS), respectively, and those for p-stage IIIA were
      17.8%, 24.8% (p = 0.0154), and 18.8% (NS), respectively. There was a tendency for
      greater survival differences between ASC and AC in earlier tumor stages. A step
      wise multivariable model demonstrated that sex, age, performance status,
      histology, tumor size, p-stage, operative method, and neoadjuvant/adjuvant
      therapy were independent prognostic factors. CONCLUSION: ASC of the lung is more
      aggressive than AC and SC. The decreased survival of patients with ASC as
      compared with either of those single histology tumors suggests the need for a
      clinical trial of adjuvant chemotherapy that includes early-stage patients.

PMID- 21737296
TI  - Myocardial metabolism and diastolic function after aortic valve replacement for
      aortic stenosis: influence of patient-prosthesis mismatch.
AB  - OBJECTIVE: This study evaluated the impact of patient-prosthesis mismatch on
      myocardial function and high-energy phosphate metabolism after aortic valve
      replacement for pure aortic stenosis. Patients with and without patient
      prosthesis mismatch were compared using magnetic resonance techniques. METHODS:
      Thirty patients who had undergone aortic valve replacement with Medtronic Mosaic
      bioprosthesis were evaluated. Fifteen patients with patient-prosthesis mismatch
      were compared to 15 matched patients without patient-prosthesis mismatch. These
      two homogeneous groups were studied for myocardial metabolism and left ventricle
      function preoperatively and at 12 months postoperatively with magnetic resonance
      imaging and (31)P spectroscopy. RESULTS: All patients experienced improvement in
      myocardial metabolism and left ventricle function. Left ventricle mass regression
      was impaired in both groups. Impaired diastolic filling was associated with
      increased left ventricle wall mass in both groups (patient-prosthesis mismatch:
      R(2) = -0.71, p = 0.002; no patient-prosthesis mismatch: R(2) = -0.88, p <
      0.001). Myocardial phosphocreatine/adenosine triphosphate ratio revealed a modest
      correlation with left ventricle function as evaluated by early acceleration peak
      (patient-prosthesis mismatch: R(2) = 0.37, p = 0.03; no patient-prosthesis
      mismatch: R(2) = 0.17, p = 0.02) and early deceleration peak (patient-prosthesis
      mismatch: R(2) = 0.30, p = 0.01; no patient-prosthesis mismatch: R(2) = 0.39, p =
      0.008). No significant correlation between the phosphocreatine/adenosine
      triphosphate ratio and left ventricle mass was found (patient-prosthesis
      mismatch: R(2) = 0.39, p = 0.6; no patient-prosthesis mismatch: R(2) = 0.40, p =
      0.08). CONCLUSION: Aortic valve replacement leads to early improvement of left
      ventricle function and myocardial metabolism in all patients regardless of the
      occurrence of patient-prosthesis mismatch.

PMID- 21737297
TI  - Editorial comment: Position paper for the use of extracorporeal life support in
      adult patients.

PMID- 21737298
TI  - Liberal use of tricuspid-valve annuloplasty during left-ventricular assist device
      implantation.
AB  - OBJECTIVE: The study aimed to determine whether liberal use of tricuspid-valve
      repair (TVr) is associated with adverse outcomes. METHODS: The study was a
      retrospective review of 51 implantable left-ventricular assist devices (LVADs)
      performed in a single center between January 2008 and December 2009. TVr using
      Edwards MC 3 annuloplasty ring was performed if there was either documented
      moderate or greater tricuspid regurgitation or severe annular dilatation.
      RESULTS: TVr was performed in 37 patients. One patient was converted to
      replacement intra-operatively. Compared with patients who did not have TVr, the
      age was similar (mean 52 vs 50 years, p=0.62), as was frequency of the
      Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)
      level 1 or 2 (43% vs 50%, p=0.13). Day 1 hemodynamics were also similar: mean
      central venous pressure (13.5 vs 14 mmHg; p=0.10) and mean pulmonary artery
      pressure (25 vs 25.6 mmHg; p=0.76), as was Day 1 bilirubin (3.1 vs 3.9 mg dl(-1),
      p=0.27). Median duration of mechanical ventilation (2 days) and inotropic support
      (5 days) and rates of bleeding were identical in both groups. Although there was
      a trend toward longer intensive care unit (ICU) stays in the TVr group (6 vs 5
      days; p=0.12), as a group these patients experienced less use of blood-product
      transfusion and less hospital length of stay. Hospital mortality was similar in
      both groups (TVr 18.9%, no TVr 21.4%, p=0.7). CONCLUSIONS: TVr can be applied
      during LVAD implantation without 'obvious' increase in perioperative risk. As
      there are theoretical benefits to eliminating tricuspid regurgitation, our data
      argue for a more liberal approach to TVr at the time of LVAD implantation.

PMID- 21737299
TI  - TNFalpha increases resting potential in isolated fibres from rat peroneus longus
      by a PKC mediated mechanism: involvement in ICU acquired polyneuromyopathy.
AB  - BACKGROUND AND AIMS: Our aim was to investigate the effect of TNFalpha on muscle
      resting potential (RP) and then in muscle excitability and to demonstrate another
      mechanism implicated in intensive care units (ICU) acquired polyneuromyopathy.
      METHODS: Experiments were carried out on adult female Wistar rats. After
      isolation of muscle fibres from peroneus longus, influence of TNFalpha was tested
      on RP by using intracellular microelectrodes. Digoxin and chelerythrin were used
      to determine the mechanism of TNFalpha action. RESULTS: First, we found that
      TNFalpha induced a concentration dependent increase of muscle RP and that this
      mechanism, which was blocked by digoxin, was due to an effect on the Na/K ATPase.
      As it was also blocked by chelerythrin it was concluded that this effect was
      mediated by PKC activation of the Na/K ATPase. CONCLUSIONS: We demonstrated that
      TNFalpha leads to a PKC mediated increase in muscle RP. Depolarization needed to
      reach the threshold voltage for muscle action potential should then be higher and
      this could be involved in the decrease in muscle excitability observed in
      acquired polyneuromyopathy.

PMID- 21737300
TI  - Tumor necrosis factor alpha induces a model of preeclampsia in pregnant baboons
      (Papio hamadryas).
AB  - Preeclampsia is a common disease of pregnancy characterised by maternal
      hypertension and proteinuria. Abnormal placentation in early pregnancy and
      abnormal cytokine and anti-angiogenic factor expression are thought to contribute
      to the clinical syndrome of endothelial dysfunction evident in the second half of
      gestation. The mechanisms underlying both the placental pathology and its
      translation to the maternal clinical syndrome are not fully understood. A model
      of preeclampsia manifest by clinically evident endothelial dysfunction (increased
      blood pressure and proteinuria) was induced by administration of low-dose TNF
      alpha for 2weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood
      pressure was monitored continuously and remotely by intra-arterial
      radiotelemetry. Following TNF-alpha infusion, there was an increase in systolic
      and diastolic blood pressure and development of proteinuria in pregnant treated
      animals, but not in pregnant saline controls nor in non-pregnant TNF-alpha
      treated animals. The treated pregnant animals also developed elevated plasma
      soluble FMS-like tyrosine kinase-1 (sFLT-1) and increased placental mRNA
      expression of sFLT-1 and soluble endoglin (sEng). These results clearly
      demonstrate that the cytokine TNF-alpha can induce the clinical and biochemical
      features of human preeclampsia. The results identify a link between cytokines,
      placental dysfunction and endothelial dysfunction resulting in a loss of maternal
      blood pressure control.

PMID- 21737301
TI  - Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF
      alpha) levels in healthy men.
AB  - Total sleep deprivation in humans is associated with increased daytime
      sleepiness, decreased performance, elevations in inflammatory cytokines, and
      hormonal/metabolic disturbances. To assess the effects of 40 h of total sleep
      deprivation (TSD) under constant and well controlled conditions, on plasma levels
      of TNF-alpha and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C
      reactive protein (CRP), sleepiness and performance, 12 healthy men (29+/-3 years)
      participated in a 5-days sleep deprivation experiment (two control nights
      followed by a night of sleep loss and one recovery night). Between 0800 and 2300
      (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling,
      multiple sleep latency, subjective levels of sleepiness and reaction time tests
      were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss.
      We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep
      deprivation) induced a significant increase in TNF-alpha (P<0.01), but there were
      no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study
      in which constant and controlled experimental conditions were realized with
      healthy subjects and in absence of psychological or physical stressors, an acute
      total sleep deprivation (from 34 h) was sufficient to induce secretion of pro
      inflammatory cytokine such as TNF-alpha, a marker more described in chronic sleep
      restriction or deprivation and as mediators of excessive sleepiness in humans in
      pathological conditions.

PMID- 21737302
TI  - A prospective analysis of prolonged sitting time and risk of renal cell carcinoma
      among 300,000 older adults.
AB  - PURPOSE: Accumulating evidence suggests an etiologic role in renal cell carcinoma
      (RCC) for physical activity. However, it is unknown if prolonged sitting, which
      is thought to be distinct from too little moderate-vigorous physical activity, is
      an independent risk factor for RCC. The authors prospectively examined the
      relationship of prolonged sitting and risk of RCC among 289,512 women and men in
      the National Institutes of Health-AARP Diet and Health Study. METHODS: From 1996
      through 2006, 1206 invasive RCC cancer cases were identified. Cox proportional
      hazards regression was used to estimate multivariate hazard ratios (HR) and 95%
      confidence intervals. RESULTS: After controlling for known risk factors for RCC,
      we did not find evidence of associations between RCC risk and time spent per day
      sitting while watching television or videos (HR(7 + hrs: < 1 hr) = 0.96 (0.66,
      1.38); p trend = 0.707) or total sitting time (HR(9 + hrs: < 3 hrs) = 1.11 (0.87,
      1.41); p trend = 0.765). CONCLUSIONS: Prolonged sitting time was not associated
      with RCC risk among men and women in this large cohort.

PMID- 21737303
TI  - The socioeconomic gradient of diabetes prevalence, awareness, treatment, and
      control among African Americans in the Jackson Heart Study.
AB  - PURPOSE: Little research has focused on the social patterning of diabetes among
      African Americans. We examined the relationship between socioeconomic status
      (SES) and the prevalence, awareness, treatment, and control of diabetes among
      African Americans. METHODS: Education, income and occupation were examined among
      4,303 participants (2,726 women and 1,577 men). Poisson regression estimated
      relative probabilities (RP) of diabetes outcomes by SES. RESULTS: The prevalence
      of diabetes was 19.6% in women and 15.9% in men. Diabetes awareness, treatment,
      and control were 90.0%, 86.8%, and 39.2% in women, respectively, and 88.2%,
      84.4%, and 35.9% in men, respectively. In adjusted models, low-income men and
      women had greater probabilities of diabetes than high-income men and women (RP,
      1.94; 95% confidence interval [CI], 1.28-2.92; and RP, 1.35; 95% CI, 1.04-1.74,
      respectively). Lack of awareness was associated with low education and low
      occupation in women (RP, 2.28; 95%CI 1.01-5.18; and RP, 2.62; 95% CI, 1.08-6.33,
      respectively) but not in men. Lack of treatment was associated with low education
      in women. Diabetes control was not patterned by SES. CONCLUSIONS: Diabetes
      prevalence is patterned by SES, and awareness and treatment are patterned by SES
      in women but not men. Efforts to prevent diabetes in African Americans need to
      address the factors that place those of low SES at higher risk.

PMID- 21737304
TI  - All-cause and cause-specific mortality among black and white North Carolina state
      prisoners, 1995-2005.
AB  - PURPOSE: We compared mortality rates among state prisoners and other state
      residents to identify prisoners' health care needs. METHODS: We linked North
      Carolina prison records with state death records for 1995-2005 to estimate all
      cause and cause-specific death rates among black and white male prisoners ages 20
      79 years and used standardized mortality ratios (SMRs) to compare these observed
      deaths with the expected number on the basis of death rates among state
      residents. RESULTS: The all-cause SMR of black prisoners was 0.52 (95% confidence
      interval, 0.48-0.57), with fewer deaths than expected from accidents, homicides,
      cardiovascular disease, and cancer. The all-cause SMR of white prisoners was 1.12
      (95% confidence interval, 1.01-1.25) with fewer deaths than expected for
      accidents but more deaths than expected from viral hepatitis, liver disease,
      cancer, chronic lower respiratory disease, and HIV. CONCLUSIONS: The mortality of
      black prisoners was lower than that of black state residents for both traumatic
      and chronic causes of death. The mortality of white prisoners was lower than that
      of white state residents for accidents but greater for several chronic causes of
      death. Future studies should investigate the effect of prisoners'
      preincarceration and in-prison morbidity, the prison environment, and prison
      health care on prisoners' patterns of mortality.

PMID- 21737305
TI  - Dependence of confounding on the target population: a modification of causal
      graphs to account for co-action.
AB  - PURPOSE: Directed acyclic graphs (DAGs) are useful tools for assessing
      confounding. However, the basic approach to detecting confounding in DAGs does
      not distinguish among various forms of interaction between the exposure and
      covariates and between different target populations for which effects are
      estimated. We propose a simple modification of DAG rules to overcome this
      limitation. METHODS: Using fundamental concepts and DAGs, we show that the basic
      approach can suggest confounding even when absent if the covariate has no effect
      in the reference population being used as the comparator for the target
      population, as occurs when the target population is the exposed and the covariate
      acts only when the exposure is present. RESULTS: We present three examples that
      illustrate this scenario and propose a simple revision to the basic approach to
      detecting confounding in DAGs that makes confounding in the presence of causal
      interaction easier to evaluate visually. This revision extends to other scenarios
      involving other target populations and variables with multiple levels.
      CONCLUSIONS: A simple modification of the basic approach to identifying
      confounding in DAGs allows more frequent exclusion of confounding when it is
      absent.

PMID- 21737306
TI  - Coming home: social functioning and the mental health of UK Reservists on return
      from deployment to Iraq or Afghanistan.
AB  - PURPOSE: There is speculation that high rates of mental illness among Reservists
      returning from deployment to Iraq and Afghanistan may be due to the challenge of
      reintegrating into civilian life. We aimed to examine the postdeployment social
      functioning of Reservists and to explore the relationship between adverse
      postdeployment experiences and subsequent mental ill health. METHODS: A sample of
      4,991 UK military personnel who had deployed to either Iraq or Afghanistan were
      asked about their postdeployment experiences with a particular focus on their
      levels of social integration, perceived support from the military, and civilian
      employment. All participants were asked to complete a series of validated
      measures of mental health. RESULTS: Compared with Regular personnel, Reservists
      were more likely to feel unsupported by the military and to have difficulties
      with social functioning in the postdeployment period. Perceived lack of support
      from the military was associated with increased reporting of probable
      posttraumatic stress disorder (PTSD) and alcohol misuse. Low levels of non
      military postdeployment social support and participation were associated with
      increased reporting of common mental disorder, probable PTSD, and alcohol misuse.
      CONCLUSIONS: Many Reservists find the transition from military deployment to
      civilian life difficult. Differences in postdeployment experiences may explain
      some of the increased rates of mental ill health among Reservists.

PMID- 21737307
TI  - The use of birth certificate data to reconstruct and validate self-reported birth
      address in a study of breast cancer and environment.
AB  - PURPOSE: We conducted a study comparing the location of addresses recorded on
      birth certificates with self-reported birth addresses provided by adults who were
      participants in the Western New York Exposure and Breast Cancer (WEB) Study. We
      also evaluated whether birth certificate residence data may be used to
      reconstruct missing self-reported birth residence information. METHODS: Subjects
      were selected from WEB study participants born in Western New York State between
      1920 and 1964 for whom we were able to obtain a New York State birth certificate.
      Addresses were geocoded and mean distance and SD between self-reported and
      certificate addresses were calculated. RESULTS: Our findings indicate good
      agreement between self-reported and birth certificate addresses (77% are within
      0.25 mile difference), and no difference in recall for cases compared with
      controls. CONCLUSIONS: This study provides evidence that self-reported and birth
      certificate-based addresses may be used together to achieve increased accuracy of
      historical records in early life when place of birth is used as a proxy for early
      life environment in relation to the development of breast cancer or other chronic
      diseases.

PMID- 21737308
TI  - Differences in the log-transformed electromyographic-force relationships of the
      plantar flexors between high- and moderate-activated subjects.
AB  - The present study examined the log-transformed electromyographic amplitude (EMG)
      versus force relationships for the medial gastrocnemius (MG) and soleus (SOL) in
      high- and moderate-activated subjects. Twenty-five (age=21+/-2 year; mass=62+/-12
      kg) participants performed six submaximal contractions (30-90% maximal voluntary
      contraction [MVC]) with the interpolated twitch technique (ITT) performed at 90%
      MVC to calculate percent voluntary activation (% VA). Sixteen participants
      with>90% VA at 90% MVC were categorized high-activated group; the remaining nine
      were the moderate-activated group. Linear regression models were fit to the log
      transformed EMG-force relationships. The slope (b value) and the antilog of the Y
      intercept (a value) were calculated. The b values from the MG EMG-force
      relationships were higher (P<0.05) for the high-activated group (1.27+/-0.13)
      than the moderate-activated group (0.88+/-0.06). The a values and p-p M-wave
      amplitude values (collapsed across twitches [superimposed and potentiated]) were
      larger (P<0.05) for the MG (1.17+/-0.40 and 8.98+/-0.46 mV) than the SOL (0.24+/
      0.07 and 4.48+/-0.20 mV) when collapsed across groups. The b value from the log
      transformed EMG-force relationships is an attractive model to determine if a
      subject has the ability to achieve high activation of their MG without muscle or
      nerve stimulation.

PMID- 21737309
TI  - Low Alberta stroke program early computed tomography score within 3 hours of
      onset predicts subsequent symptomatic intracranial hemorrhage in patients treated
      with 0.6 mg/kg Alteplase.
AB  - BACKGROUND: The significance of early ischemic changes (EICs) on computed
      tomography (CT) in selecting candidates for thrombolysis remains controversial.
      The Alberta Stroke Program Early CT Score (ASPECTS) provides a semiquantitative
      scale that scores EICs within the middle cerebral artery territory using a 10
      point grading system. We examined whether ASPECTS can predict the response to
      intravenous thrombolysis within 3 hours of stroke onset and incidence of
      secondary hemorrhage. METHODS: Data from the Japan Alteplase Clinical Trial (J
      ACT), in which 103 patients were included, were evaluated to assess the efficacy
      and safety of 0.6 mg/kg alteplase within 3 hours. All CT hardcopies were
      reevaluated retrospectively using the ASPECTS system. Multivariate logistic
      regression analysis was undertaken to determine whether an effect of ASPECTS
      existed on a defined favorable outcome as 0 or 1 on the modified Rankin Scale at
      3 months, and symptomatic intracranial hemorrhage (sICH) within 36 hours.
      RESULTS: The median ASPECTS value was 10 (range 3 to 10), and 56.3% revealed no
      evidence of EICs. ASPECTS had no effect on the patients' outcome, although a
      higher age and National Institutes of Health Stroke Scale score were negatively
      associated with a favorable outcome. On the other hand, lower ASPECTS was
      significantly associated with sICH (odds ratio [OR] 2.224; 95% confidence
      interval [CI] 1.227-4.032; P = .0084) and systolic blood pressure (OR 1.090; 95%
      CI 1.007-1.180; P = .0323) and the pre-ictal use of antiplatelet medications (OR
      15.551; 95% CI 1.144-211.374; P = .0393). CONCLUSIONS: In J-ACT, patients with
      low ASPECTS values have an increased risk of thrombolysis-related sICH.

PMID- 21737310
TI  - The first Indian-origin family with genetically proven cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL).
AB  - We report the first family of Indian origin known to be affected by cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL). Seventeen members of the family spanning 3 generations had neurologic
      syndromes compatible with CADASIL, of whom 5 were genetically confirmed carriers
      of the Notch3 gene R141C mutation in exon 4 (421(C->T) and 141(Cys->Arg)). Our
      report highlights that CADASIL not only occurs sporadically in South Asians, but
      also may account for stroke in South Asians with a strong family history.
      Furthermore, the similarity of clinical presentations described here to those
      typical for Caucasian case series suggests that the CADASIL phenotype is
      preserved across racial groups.

PMID- 21737311
TI  - Dreaming and cognition in patients with frontotemporal dysfunction.
AB  - Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have
      hallucinations and mild cognitive dysfunction. The objective of this work was to
      study dreams in PD and TLE patients using a common functional model of dream
      production involving the limbic and paralimbic structures. Dreams were
      characterised in early-stage PD (19 males) and TLE patients (52) with dream
      diaries classified by the Hall van de Castle system and were compared with
      matched controls. In PD, there were significant differences between patients'
      dreams and those of controls: animals, physical aggression, and a befriender were
      more common in patients, and aggressor and bodily misfortunes were less common.
      The dreams of patients with frontal dysfunction showed more aggressive features.
      TLE patients had lower recall than PD patients and a higher proportion of dreams
      involving family and familiar settings, lower proportions involving success, and
      a higher incidence of frontal dysfunction. The dreams of PD and TLE patients
      share important features.

PMID- 21737312
TI  - An individualized intervention to foster optimal antiretroviral treatment-taking
      behavior among persons living with HIV: a pilot randomized controlled trial.
AB  - The key to the success of antiretroviral (ARV) treatment is optimal treatment
      taking. However, people living with HIV (PLWH) have problems sustaining this
      behavior. An intervention to facilitate optimal ARV treatment taking was
      developed using the intervention mapping approach. A pilot randomized controlled
      trial was conducted to evaluate the feasibility, acceptability, and effects of
      this intervention on optimal ARV treatment taking and on viral and immunologic
      outcomes. Over the 9 months of recruitment, 76 PLWH were referred. A total of 51
      participants were enrolled in the study. All but three experimental participants
      attended at least one of the four intervention sessions. At 12 and 24 weeks
      respectively, the HIV RNA level was undetectable for 34.8% and 56.5% of controls
      and 78.6% and 89.3% of experimental participants (p = .056). The results are
      compelling and suggest that this intervention is acceptable to PLWH and that
      further formal testing is worth considering.

PMID- 21737313
TI  - Clinical depression and condom use attitudes and beliefs among African American
      adolescent females.
AB  - Depression, HIV, and other sexually transmitted diseases (STDs) are growing
      concerns among African American adolescent females. Theoretical models contribute
      to identification of mediators of condom use; however, minimal research has
      addressed the explicit relationship between clinical depression and condom use in
      African American adolescent females. The authors report results from quantitative
      surveys with clinically depressed (n = 64) and nondepressed (n = 64) African
      American adolescent females in two large metropolitan cities in the eastern
      United States. Theoretical mediators of condom use in the study sample-attitudes,
      subjective norms, perceived behavioral control, and intentions-were investigated.
      Significant differences existed between the groups in condom use frequency (U =
      356.5, p = .037); however, there were no statistically significant differences in
      condom use attitudes and beliefs. Although clinically depressed and nondepressed
      African American adolescent females may hold similar attitudes and beliefs about
      condom use, differences in condom use frequency may be a psychopathologic
      occurrence.

PMID- 21737314
TI  - Double calcaneal osteotomy using single, dual-function screw fixation technique.
AB  - Historically, a variety of fixation techniques for calcaneal osteotomies have
      been used. The prevention of postoperative sequelae, including delayed or
      nonunion of the osteotomy sites and minimization of soft tissue damage, is always
      a primary consideration for foot and ankle surgeons. The present report describes
      a fixation technique for a double calcaneal osteotomy that entails use of a
      single screw that functions as both a positional tool, as well as a compressive
      fixation device. This technique provides compressive and positional qualities and
      decreases the amount of soft tissue disruption to the surgical site.

PMID- 21737315
TI  - Posterior approach using anterior ankle arthrodesis locking plate for
      tibiotalocalcaneal arthrodesis.
AB  - Tibiotalocalcaneal arthrodesis is a successful treatment for patients with severe
      pain and functional disability in the ankle and subtalar joint. Patients with
      post-traumatic ankle and subtalar joint arthritis, and/or Charcot deformity,
      often present with compromised skin and soft tissue structures. In the present
      report, we describe a technique using an anterior ankle arthrodesis locking plate
      placed posteriorly to obtain hindfoot and ankle fusion. This technique, which
      uses the well vascularized, thick, posterior soft tissue envelope, provides very
      good exposure of the articular surfaces for resection and tibiotalocalcaneal
      fusion. The technique provides a valuable option for patients with compromised
      skin and soft tissue structures over aspects of the ankle that make other
      approaches risky and complicated.

PMID- 21737316
TI  - Is it time to lower the recommended screening age for colorectal cancer?
AB  - BACKGROUND: Overall, colorectal cancer (CRC) incidence in the US has decreased
      over the last 30 years, yet it has increased in patients younger than 50. Cancers
      in this population are more aggressive and advanced at diagnosis. Our goal was to
      determine if screening should begin at a younger age. To accomplish this, we
      analyzed the rates of change in CRC incidence, and compared the incidence with
      that of cervical cancer (CC), which is screened earlier. Locations of CRC were
      compared to determine the appropriate screening method. STUDY DESIGN: Incidence
      statistics were obtained from the Cancer Query System of the SEER database. Data
      were obtained from 1987 to 2006 in age groups of 5-year increments from 0 to 4
      years old to 85+ years old for incidences of colon, rectal, and overall CRC.
      Combined data from 2002 to 2006 were queried to determine the locations of tumors
      and the overall incidence of CRC and CC at different ages. RESULTS: Across age
      groups 20 to 49, CRC incidence was higher in 2006 than in 1987. The most
      significant increase was from age 40 to 44, where CRC increased from a low of
      10.7 per 100,000 in 1988 to 17.9 per 100,000 in 2006 (67%). Colon and rectal
      cancer increased 56% and 94%, respectively. People older than 50 had decreasing
      incidences. Approximately 30% of cancers in patients aged 35 to 49 occurred
      proximal to the splenic flexure. The incidence of CRC cancer equaled and
      subsequently surpassed CC in the 40 to 44 age group. CONCLUSIONS: The most
      significant increase in CRC has occurred in patients ages 40 to 44. Patients over
      50 continued to see a decline. Many of these cancers would be missed with
      sigmoidoscopy. Consideration should be given for age-based colonoscopic screening
      beginning at age 40, an age at which the incidence mirrors other accepted
      screened cancers.

PMID- 21737317
TI  - Skint-1 identifies a common molecular mechanism for the development of interferon
      gamma-secreting versus interleukin-17-secreting gammadelta T cells.
AB  - Murine T cell development begins with the generation of a unique
      Vgamma5(+)Vdelta1(+) epidermal gammadelta T cell compartment and a unique, more
      broadly distributed Vgamma6(+)Vdelta1(+) subset that is an important source of
      interleukin-17 (IL-17). This study showed that these respective functional
      programs were determined by Skint-1, a thymic epithelial cell determinant. By
      engaging Skint-1(+) cells, Vgamma5(+)Vdelta1(+) thymocytes induced an Egr3
      mediated pathway, provoking differentiation and the potential to produce IFN
      gamma while suppressing the gammadelta T cell lineage factor, Sox13, and a
      RORgammat transcription factor-associated IL-17-producing capacity. Hence, the
      functions of the earliest T cells are substantially preprogrammed in the thymus.
      Additionally, the phenotype of Skint-1-selected fetal thymocytes permitted
      identification in the adult thymus of an analogous gene regulatory network
      regulated by the gammadelta T cell receptor. Hence, these observations describe a
      molecular pathway by which distinct stress-responsive lymphocyte repertoires may
      emerge throughout ontogeny and offer parallels with emerging perspectives on the
      functional selection of other lymphoid cells.

PMID- 21737318
TI  - Paratubal borderline tumor diagnosed in the adolescent period: a case report and
      review of the literature.
AB  - BACKGROUND: Borderline paratubal cysts are rare entities. These tumors are
      identified as epithelial proliferation without stromal invasion. CASE: A 19-year
      old virgin patient was admitted to our clinic with abdominal pain and nausea. The
      sonographic evaluation showed a left adnexal mass 89 * 80 mm in diameter with
      solid tissue projections. Doppler examination revealed no significant blood
      supply. At surgery, a torsed left paratubal cyst 10 cm in diameter and normal
      bilateral ovaries were encountered. Cystectomy was performed and of frozen
      section revealed a borderline Fallopian tube neoplasm. Final pathology review was
      reported as a serous borderline paratubal tumor. CONCLUSION: The evaluation of
      the structure of cyst by ultrasound and the performance of intraoperative frozen
      section analysis are two important issues to diagnose the nature of a cyst.
      Fertility-sparing surgery is the main point of management.

PMID- 21737319
TI  - Internet resources cataloguing inherited disorders in dogs.
AB  - Up-to-date annotated catalogues of known inherited disorders in dogs are freely
      available on the Internet, providing vital information to existing and
      prospective dog owners, dog breeders, veterinarians, geneticists and others
      interested in the occurrence and control of inherited disorders. These resources
      are the Canine Inherited Disorders Database (CIDD), Inherited Diseases in Dogs
      (IDID) and Online Mendelian Inheritance in Animals (OMIA) the latter associated
      with Listing of Inherited Disorders in Animals (LIDA). The history and features
      of these resources are summarised.

PMID- 21737320
TI  - Researcher responsibilities and genetic counseling for pure-bred dog populations.
AB  - Breeders of dogs have ethical responsibilities regarding the testing and
      management of genetic disease. Molecular genetics researchers have their own
      responsibilities, highlighted in this article. Laboratories offering commercial
      genetic testing should have proper sample identification and quality control,
      official test result certificates, clear explanations of test results and
      reasonably priced testing fees. Providing test results to a publicly-accessible
      genetic health registry allows breeders and the public to search for health
      tested parents to reduce the risk of producing or purchasing affected offspring.
      Counseling on the testing and elimination of defective genes must consider the
      effects of genetic selection on the population. Recommendations to breed quality
      carriers to normal-testing dogs and replacing them with quality normal-testing
      offspring will help to preserve breeding lines and breed genetic diversity.

PMID- 21737321
TI  - Genetic diversity, inbreeding and breeding practices in dogs: results from
      pedigree analyses.
AB  - Pedigree analysis constitutes a classical approach for the study of the evolution
      of genetic diversity, genetic structure, history and breeding practices within a
      given breed. As a consequence of selection pressure, management in closed
      populations and historical bottlenecks, many dog breeds have experienced
      considerable inbreeding and show (on the basis of a pedigree approach) comparable
      diversity loss compared to other domestic species. This evolution is linked to
      breeding practices such as the overuse of popular sires or mating between related
      animals. The popular sire phenomenon is the most problematic breeding practice,
      since it has also led to the dissemination of a large number of inherited
      defects. The practice should be limited by taking measures such as restricting
      the number of litters (or offspring) per breeding animal.

PMID- 21737322
TI  - Canine hip and elbow dysplasia in UK Labrador retrievers.
AB  - This paper examines the outcomes from recent genetic analyses of hip and elbow
      scores from British Veterinary Association (BVA)/UK Kennel Club (KC) screening
      programmes targeted at reducing the prevalence of hip dysplasia (HD) and elbow
      dysplasia in UK Labrador retrievers. The analyses made use of 25,243 hip scores
      and 3613 elbow scores. Heritabilities (+/- standard error) for hip score,
      analysed on a log scale, and for elbow score were 0.35+/-0.02 and 0.19+/-0.04,
      respectively, with a genetic correlation of 0.41+/-0.09. For both hip and elbow
      scores, there was a near perfect genetic correlation between the left and right
      joint; analysis of hip score showed a predictive benefit of using the total of
      left and right scores rather than worst score and the benefit of using all
      component scores rather than their aggregate score. Downward genetic trends were
      observed in both hip and elbow scores, although the latter was consistent with it
      being correlated to response to genetic change in hip score. Estimated breeding
      values (EBVs) offered substantial benefits in accuracy and hence genetic progress
      when compared to the use of phenotypes for both hip and elbow scores. There are
      major opportunities for improving selection against elbow dysplasia through the
      use of bivariate evaluations, although progress against dysplasia would be
      improved by more widespread elbow scoring. The studies highlighted a number of
      ways in which data recording for addressing complex traits may be improved in the
      future. Ongoing advances in genomic technology may be utilised for increasing the
      rate of genetic progress in selection against HD and for complex diseases in
      general, through the use of genomic evaluations.

PMID- 21737323
TI  - Canine genetics: a very special issue.

PMID- 21737324
TI  - Genetic evaluation of elbow scores and the relationship with hip scores in UK
      Labrador retrievers.
AB  - A linear mixed model analysis of elbow and hip score data from UK Labrador
      retrievers was used to estimate the heritability of elbow score (0.16-0.19) and
      to determine a moderate and beneficial genetic correlation with hip score (0.40).
      A small improvement in the genetic trend of elbow score was observed during the
      years 2000-2008, equivalent to avoiding only the worst 3-4% of scored dogs for
      breeding, but close to what may have been anticipated if the current British
      Veterinary Association-approved guidelines were followed. Calculations suggested
      that a correlated response to indirect selection on hip score may elicit a
      greater response than direct selection on elbow score and that the genetic trend
      in elbow score may be explained as a consequence of the stronger selection
      pressure that has been placed on hip score. Increases in the accuracy of
      estimated breeding values for elbow score of 4-7% for dogs with elbow data only
      and 7-11% for dogs with both hip and elbow score were observed from bivariate
      analysis of elbow and hip data. A selection index confirmed the benefits of
      bivariate analysis of elbow and hip score data by identifying increases in
      accuracy (directly related to the response to selection) of 14% from the use of
      optimum coefficients compared to use of hip data only. The quantified genetic
      correlation means that hip score effectively acts as a 'secondary indicator' of
      elbow score in this breed and the preponderance of hip data means that it acts as
      a major source of information that may be used to improve the accuracy of
      estimates of genetic risk for elbow dysplasia.

PMID- 21737325
TI  - Response to rituximab in 3 children with opsoclonus-myoclonus syndrome resistant
      to conventional treatments.
AB  - We report the 1 year follow-up of 3 children affected by non-paraneoplastic
      Opsoclonus-Myoclonus Syndrome (OMS) resistant to conventional therapies
      (steroids, ACTH and intravenous immunoglobulins) who were treated with an anti
      CD20 monoclonal antibody (rituximab). Treatment response was recorded on the
      basis of an international score at 0, 3, 6, 9 and 12 months. Despite the long
      disease duration and the numerous previously administered treatments, all
      patients underwent rapid and persistent neurological recovery following rituximab
      administration, thus suggesting a potential role of this drug even in pre-treated
      patients.

PMID- 21737326
TI  - Use of polyphase continuous excitation based on the Frank sequence in EPR.
AB  - Polyphase continuous excitation based on the Frank sequence is suggested as an
      alternative to single pulse excitation in EPR. The method allows reduction of the
      source power, while preserving the excitation bandwidth of a single pulse. For
      practical EPR implementation the use of a cross-loop resonator is essential to
      provide isolation between the spin system and the resonator responses to the
      excitation. Provided that a line broadening of about 5% is acceptable, the
      cumulative turning angle of the magnetization vector generated by the excitation
      sequence can be quite large and can produce signal amplitudes that are comparable
      to that achieved with a higher power 90 degrees  pulse.

PMID- 21737327
TI  - Cardinal series to restore NMR-signals dominated by strong inhomogeneous
      broadening.
AB  - We have devised two numerical methods of restoring incomplete band-limited NMR
      signals to integrity by either interpolating or extrapolating them. Both methods
      are based on use of the finite cardinal series, whose filtering properties were
      discussed previously, to model signals. They require no prior knowledge about the
      system under study, but only that the available parts of the signal were
      oversampled enough. The methods were tested on two types of computer-simulated
      signal. It proved superior to the linear prediction methods and Lagrange
      interpolation when applied to signals measured in highly inhomogeneous magnetic
      fields. The extrapolation method was then applied to restore experimentally
      measured refocused FID-signals of a porous medium. The missing parts of the
      signal of up to several times the size of its Nyquist period could be recovered
      by either method.

PMID- 21737328
TI  - Cerebral folate deficiency: a neurometabolic syndrome?
AB  - BACKGROUND: Cerebral folate deficiency (CFD) is increasingly recognized in
      various neurological conditions, raising the question of whether it might
      represent a clear-cut clinical syndrome. METHODS: Retrospective analysis of
      patients with low cerebral spinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF)
      values was performed. RESULTS: 58 pediatric patients with low (-2nd to -3rd
      standard deviation) and 45 patients with very low 5MTHF values (<3rd standard
      deviation) were identified, including 22 patients with defined underlying
      neurological conditions. The leading symptoms were mental retardation (n=84),
      motor retardation (n=75), epilepsy (n=53), ataxia (n=44) and pyramidal tract
      signs (n=37). There was no relationship between 5MTHF levels and the severity of
      clinical disease, the duration of clinical disease, distinct neurological
      symptoms and antiepileptic drug treatment, respectively. Genetical analysis for
      mutations in the folate receptor 1 gene proved normal in all 16 children studied.
      CONCLUSIONS: For the majority of patients CFD is not a clear-cut neurometabolic
      syndrome but the common result of different genetic, metabolic or unknown
      processes. Nevertheless, CFD may represent a treatable disease-modifying factor
      which should therefore be addressed in prospective studies.

PMID- 21737329
TI  - The Ripoptosome, a signaling platform that assembles in response to genotoxic
      stress and loss of IAPs.
AB  - A better understanding of the mechanisms through which anticancer drugs exert
      their effects is essential to improve combination therapies. While studying how
      genotoxic stress kills cancer cells, we discovered a large ~2MDa cell death
      inducing platform, referred to as "Ripoptosome." It contains the core components
      RIP1, FADD, and caspase-8, and assembles in response to genotoxic stress-induced
      depletion of XIAP, cIAP1 and cIAP2. Importantly, it forms independently of TNF,
      CD95L/FASL, TRAIL, death-receptors, and mitochondrial pathways. It also forms
      upon Smac-mimetic (SM) treatment without involvement of autocrine TNF.
      Ripoptosome assembly requires RIP1's kinase activity and can stimulate caspase-8
      mediated apoptosis as well as caspase-independent necrosis. It is negatively
      regulated by FLIP, cIAP1, cIAP2, and XIAP. Mechanistically, IAPs target
      components of this complex for ubiquitylation and inactivation. Moreover, we find
      that etoposide-stimulated Ripoptosome formation converts proinflammatory
      cytokines into prodeath signals. Together, our observations shed new light on
      fundamental mechanisms by which chemotherapeutics may kill cancer cells.

PMID- 21737330
TI  - cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell
      death complex differentially regulated by cFLIP isoforms.
AB  - The intracellular regulation of cell death pathways by cIAPs has been enigmatic.
      Here we show that loss of cIAPs promotes the spontaneous formation of an
      intracellular platform that activates either apoptosis or necroptosis. This 2 MDa
      intracellular complex that we designate "Ripoptosome" is necessary but not
      sufficient for cell death. It contains RIP1, FADD, caspase-8, caspase-10, and
      caspase inhibitor cFLIP isoforms. cFLIP(L) prevents Ripoptosome formation,
      whereas, intriguingly, cFLIP(S) promotes Ripoptosome assembly. When cIAPs are
      absent, caspase activity is the "rheostat" that is controlled by cFLIP isoforms
      in the Ripoptosome and decides if cell death occurs by RIP3-dependent necroptosis
      or caspase-dependent apoptosis. RIP1 is the core component of the complex. As
      exemplified by our studies for TLR3 activation, our data argue that the
      Ripoptosome critically influences the outcome of membrane-bound receptor
      triggering. The differential quality of cell death mediated by the Ripoptosome
      may cause important pathophysiological consequences during inflammatory
      responses.

PMID- 21737331
TI  - [Pre-surgical nursing visit: evaluation of its effectiveness and patient
      perception].

PMID- 21737332
TI  - Super-spreaders in infectious diseases.
AB  - Early studies that explored host-pathogen interactions assumed that infected
      individuals within a population have equal chances of transmitting the infection
      to others. Subsequently, in what became known as the 20/80 rule, a small
      percentage of individuals within any population was observed to control most
      transmission events. This empirical rule was shown to govern inter-individual
      transmission dynamics for many pathogens in several species, and individuals who
      infect disproportionately more secondary contacts, as compared to most others,
      became known as super-spreaders. Studies conducted in the wake of the severe
      acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super
      spreading events, most individuals infect few, if any, secondary contacts. The
      analysis of SARS transmission, and reports from other outbreaks, unveil a complex
      scenario in which super-spreading events are shaped by multiple factors,
      including co-infection with another pathogen, immune suppression, changes in
      airflow dynamics, delayed hospital admission, misdiagnosis, and inter-hospital
      transfers. Predicting and identifying super-spreaders open significant medical
      and public health challenges, and represent important facets of infectious
      disease management and pandemic preparedness plans.

PMID- 21737333
TI  - Diabetic foot infection: a critical review of recent randomized clinical trials
      on antibiotic therapy.
AB  - Controlled clinical trials are essential tools for evaluating the efficacy of
      antibiotic treatment against infection, but the results of such trials critically
      depend on sensitive, reproducible, and feasible outcome measures. We reviewed
      randomized controlled trials on the antibiotic treatment of diabetic foot
      infection published between 1999 and 2009 in terms of quality and endpoints.
      Discrepancies in study design, inclusion criteria, statistical methodology, and
      the varying definitions of both clinical and microbiological endpoints between
      the published studies, make it difficult to compare them, as well as to determine
      which regimen may be the most appropriate for patients with diabetic foot
      infection.

PMID- 21737334
TI  - [Intensity modulated radiotherapy as adjuvant post-operative treatment for
      retroperitoneal sarcoma: acute toxicity].
AB  - PURPOSE: To assess the acute toxicity of intensity modulated radiotherapy as post
      operative adjuvant treatment for retroperitoneal sarcoma. PATIENTS AND METHODS:
      Patients who received adjuvant intensity modulated radiotherapy from January 2009
      to September 2010 were retrospectively reviewed. RESULTS: Fourteen patients
      entered the study (seven primary tumours and seven relapses). All tumours were
      liposarcoma and had macroscopically complete resection, epiploplasty was
      systematically realized. Median tumour size was 21 cm (range: 15-45), median
      planning target volume was 580 cm(3) (range: 329-1172) and median prescribed dose
      was 50.4 Gy (range: 45-54). Median follow-up was 11.5 months (range: 2-21.4).
      Acute toxicity was mild: acute digestive toxicity grade 1-2 occurred in 12/14
      patients (86%). However, there was no weight loss of more than 5% during
      radiotherapy and no treatment interruption was required. Two months after
      completion of radiotherapy, digestive toxicity grade 1 remained present in 1/14
      patients (7%). One case of grade 3 toxicity occurred during follow-up (transient
      abdominal pain). Three relapses occurred: two were outside treaded volume and one
      was both in and outside treated volume. CONCLUSIONS: Intensity modulated
      radiotherapy in the postoperative setting of retroperitoneal sarcoma provides low
      acute toxicity. Longer follow-up is needed to assess late toxicity, especially
      for bowel, kidney and radio-induced malignancies.

PMID- 21737335
TI  - [Double strand break repair, one mechanism can hide another: alternative non
      homologous end joining].
AB  - DNA double strand breaks are major cytotoxic lesions encountered by the cells.
      They can be induced by ionizing radiation or endogenous stress and can lead to
      genetic instability. Two mechanisms compete for the repair of DNA double strand
      breaks: homologous recombination and non-homologous end joining (NHEJ).
      Homologous recombination requires DNA sequences homology and is initiated by
      single strand resection. Recently, advances have been made concerning the major
      steps and proteins involved in resection. NHEJ, in contrast, does not require
      sequence homology. The existence of a DNA double strand break repair mechanism,
      independent of KU and ligase IV, the key proteins of the canonical non homologous
      end joining pathway, has been revealed lately and named alternative non
      homologous end joining. The hallmarks of this highly mutagenic pathway are
      deletions at repair junctions and frequent use of distal microhomologies. This
      mechanism is also initiated by a single strand resection of the break. The aim of
      this review is firstly to present recent data on single strand resection, and
      secondly the alternative NHEJ pathway, including a discussion on the fidelity of
      NHEJ. Based on current knowledge, canonical NHEJ does not appear as an
      intrinsically mutagenic mechanism, but in contrast, as a conservative one. The
      structure of broken DNA ends actually dictates the quality repair of the
      alternative NHEJ and seems the actual responsible for the mutagenesis attributed
      beforehand to the canonical NHEJ. The existence of this novel DNA double strand
      breaks repair mechanism needs to be taken into account in the development of
      radiosensitizing strategies in order to optimise the efficiency of radiotherapy.

PMID- 21737336
TI  - The prison setting as a place of enforced residence, its mental health effects,
      and the mental healthcare implications.
AB  - The subject of place is salient certainly when deliberating the health of
      prisoners as a social group. This paper provides an overview and assessment of
      health and place in relation to mental health and the prison locale. Particular
      attention is devoted to prison culture, both staff and inmate. The incarceration
      experience (i.e. the nature of enforced residence in the prison environment) can
      affect negatively prisoners' mental health. The mental health of the prison
      population is poor, and mental health services in the prison setting have need of
      further improvement. However, the provision of mental healthcare and the pursuit
      of good mental health in the prison milieu are challenging. The prison-based
      exceedingly complex-three-way relationship between culture-mental and health
      mental healthcare is debated.

PMID- 21737337
TI  - Segmentation of the heart and great vessels in CT images using a model-based
      adaptation framework.
AB  - Recently, model-based methods for the automatic segmentation of the heart
      chambers have been proposed. An important application of these methods is the
      characterization of the heart function. Heart models are, however, increasingly
      used for interventional guidance making it necessary to also extract the attached
      great vessels. It is, for instance, important to extract the left atrium and the
      proximal part of the pulmonary veins to support guidance of ablation procedures
      for atrial fibrillation treatment. For cardiac resynchronization therapy, a heart
      model including the coronary sinus is needed. We present a heart model comprising
      the four heart chambers and the attached great vessels. By assigning individual
      linear transformations to the heart chambers and to short tubular segments
      building the great vessels, variable sizes of the heart chambers and bending of
      the vessels can be described in a consistent way. A configurable algorithmic
      framework that we call adaptation engine matches the heart model automatically to
      cardiac CT angiography images in a multi-stage process. First, the heart is
      detected using a Generalized Hough Transformation. Subsequently, the heart
      chambers are adapted. This stage uses parametric as well as deformable mesh
      adaptation techniques. In the final stage, segments of the large vascular
      structures are successively activated and adapted. To optimize the computational
      performance, the adaptation engine can vary the mesh resolution and freeze
      already adapted mesh parts. The data used for validation were independent from
      the data used for model-building. Ground truth segmentations were generated for
      37 CT data sets reconstructed at several cardiac phases from 17 patients.
      Segmentation errors were assessed for anatomical sub-structures resulting in a
      mean surface-to-surface error ranging 0.50-0.82mm for the heart chambers and 0.60
      1.32mm for the parts of the great vessels visible in the images.

PMID- 21737338
TI  - Automated macular pathology diagnosis in retinal OCT images using multi-scale
      spatial pyramid and local binary patterns in texture and shape encoding.
AB  - We address a novel problem domain in the analysis of optical coherence tomography
      (OCT) images: the diagnosis of multiple macular pathologies in retinal OCT
      images. The goal is to identify the presence of normal macula and each of three
      types of macular pathologies, namely, macular edema, macular hole, and age
      related macular degeneration, in the OCT slice centered at the fovea. We use a
      machine learning approach based on global image descriptors formed from a multi
      scale spatial pyramid. Our local features are dimension-reduced local binary
      pattern histograms, which are capable of encoding texture and shape information
      in retinal OCT images and their edge maps, respectively. Our representation
      operates at multiple spatial scales and granularities, leading to robust
      performance. We use 2-class support vector machine classifiers to identify the
      presence of normal macula and each of the three pathologies. To further
      discriminate sub-types within a pathology, we also build a classifier to
      differentiate full-thickness holes from pseudo-holes within the macular hole
      category. We conduct extensive experiments on a large dataset of 326 OCT scans
      from 136 subjects. The results show that the proposed method is very effective
      (all AUC>0.93).

PMID- 21737339
TI  - Empirical support for higher-order theories of conscious awareness.
AB  - Higher-order theories of consciousness argue that conscious awareness crucially
      depends on higher-order mental representations that represent oneself as being in
      particular mental states. These theories have featured prominently in recent
      debates on conscious awareness. We provide new leverage on these debates by
      reviewing the empirical evidence in support of the higher-order view. We focus on
      evidence that distinguishes the higher-order view from its alternatives, such as
      the first-order, global workspace and recurrent visual processing theories. We
      defend the higher-order view against several major criticisms, such as prefrontal
      activity reflects attention but not awareness, and prefrontal lesion does not
      abolish awareness. Although the higher-order approach originated in philosophical
      discussions, we show that it is testable and has received substantial empirical
      support.

PMID- 21737340
TI  - Role of AMP-18 in oral mucositis.
AB  - Oral mucositis (OM) is a devasting toxicity associated with cytotoxic cancer
      therapy. Antrum mucosal protein (AMP)-18 and a synthetic peptide surrogate,
      exhibit cell protective and mitogenic properties in in vitro and in vivo models
      of gastrointestinal epithelial cell injury. The mucosal barrier-protective
      effects may be mediated by AMP-18's capacity to increase accumulation of specific
      tight junction (TJ) and adherens junction proteins, and also protect against
      their loss after injury. Here we asked if AMP peptide could protect the oral
      mucosa and speed healing from radiation-induced injury. We found AMP peptide
      prevented radiation-induced OM in a murine model. The peptide also stimulated
      HaCaT cell growth used to model the oral mucosa. Binding of recombinant human
      (rh) AMP-18 to the plasma membrane of keratinocytes in normal human oral mucosal
      tissue suggested that its effects may be receptor mediated. Using an immobilized
      His-tagged rhAMP-18 fusion protein the receptor was identified as the
      cholecystokinin-B/gastrin receptor (CCKBR) by affinity purification and mass
      spectrometry analysis. CCKBR was expressed and co-immunoprecipitated with
      exogenous rhAMP-18 in diverse epithelial cell lines. Immunofluorescence staining
      revealed that rhAMP-18 colocalized with CCKBR on the surface of CCKBR-transfected
      cells. Furthermore, rhAMP-18-stimulated signaling pathways were blocked by a
      CCKBR-specific antagonist, YM022. rhAMP-18 enhanced viability and growth of CCKBR
      transfected, but not empty vector-transfected cells. These results suggest the
      importance of epithelial junctional integrity in the pathogenesis of OM and
      demonstrate that AMP-18, by targeting TJ proteins through the activation of
      CCKBR, could provide a novel strategy for the prevention and treatment of OM.

PMID- 21737341
TI  - Vibrational and electronic spectra of 9,10-dihydrobenzo(a)pyren-7(8H)-one and
      7,8,9,10-tetrahydrobenzo(a)pyrene: an experimental and computational study.
AB  - The molecular geometries, vibrational and UV-vis spectra of 9,10
      dihydrobenzo(a)pyrene-7(8H)-one (9,10-H(2)BaP) and 7,8,9,10
      tetrahydrobenzo(a)pyrene (7,8,9,10-H(4)BaP) were investigated using density
      functional theory (DFT-B3LYP), with the triple-zeta 6-311+G(d,p) and Dunning's cc
      pVTZ basis sets. From the comparison of infrared experimental and calculated
      infrared, and Raman data comprehensive assignments are made. The calculated
      infrared frequencies below 1800 cm(-1) are in good agreement with experimental
      data, with an average deviation of <4 cm(-1). Using the B3LYP/6-311+G(d,p)//TD
      B3LYP/6-311G(d,p) level of theory, transition energies, and oscillator strengths
      of the 30 lowest electronic absorption bands are assigned to pi-pi* transitions,
      with good qualitative agreement between experimental and simulated absorption
      data. In addition, the HOMO-LUMO gaps and their chemical hardness were analyzed.

PMID- 21737342
TI  - Vibrational spectra and first order hyperpolarizability studies of dimethyl amino
      pyridinium 4-nitrophenolate 4-nitrophenol.
AB  - Vibrational spectra of the organic nonlinear optical crystallized dimethyl amino
      pyridinium 4-nitrophenolate 4-nitrophenol have been recorded and analyzed. The
      spectral interpretation has been done based on the density functional theory
      using the standard B3LYP/LANL2DZ basis set. Total energy distribution is
      calculated using the scaled quantum mechanic program. Natural bond orbital
      analysis is also used to explain the inter and intra molecular hydrogen bonding.
      The relative second harmonic efficiency of the compound is found to be 15 times
      greater than that of KDP. The effect of intermolecular hydrogen bonding between
      the phenolate ion of 4-nitrophenol with N-atom of pyridine ring is sufficiently
      more, enhancing the beta value which is the required property of a system to be
      NLO active.

PMID- 21737343
TI  - A novel spectrofluorometric method for the determination of methiocarb using an
      amphiphilic p-sulfonatocalix[4]arene.
AB  - The characteristics of host-guest complexation between tetrabutyl ether
      derivatives of p-sulfonatocalix[4]arene (SC4Bu) and methiocarb [3,5-dimethyl-4
      (methylthio) phenyl methylcarbamate] were investigated by fluorescence
      spectrometry. Upon addition of methiocarb, the fluorescence intensity of SC4Bu
      was quenched regularly and a slight red shift was observed for the maximum
      emission peak. These results indicated that the SC4Bu-methiocarb complex was
      formed a 1:1 mole ratio. An association constant of 1.67*10(4) L mol(-1) was
      calculated by applying a deduced equation. The interaction mechanism of the
      inclusion complex was discussed. Based on the results, a novel
      spectrofluorimetric method was described for the determination of methiocarb with
      a detection limit at 0.05 MUg mL(-1). This method is very simple and shows high
      sensitivity and selectivity. Moreover, the proposed method was successfully
      applied to the determination of methiocarb in water samples.

PMID- 21737344
TI  - Alteration in surface muscle electrical anisotropy in the rat SOD1 model of
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To evaluate the effects of progressive neurogenic change on surface
      measured anisotropy via study in the rat superoxide dismutase 1 (SOD1) G93A
      amyotrophic lateral sclerosis (ALS) model. METHODS: Eight male ALS rats were
      studied over a period of 10 weeks. In each, the 20 kHz to 1 MHz electrical
      impedance of the gastrocnemius-soleus complex was measured with electrodes placed
      at 0 degrees  and at 90 degrees  relative to the major muscle fiber direction.
      The major outcome measure, the anisotropy difference (AD) for each of the
      resistance, reactance, and phase, was calculated as 90-0 degrees  values.
      RESULTS: All three parameters showed substantial alterations with disease
      progression. However, the phase AD demonstrated the most substantial change,
      increasing from 1.8+/-1.58 degrees  to 10.2+/-2.13 degrees  (mean+/-standard
      error) comparing the first and last set of measurements (p=0.028). CONCLUSIONS:
      Anisotropy increases substantially with disease progression in the ALS rat.
      SIGNIFICANCE: Measurement of surface electrical anisotropy offers a non-invasive
      means for quantifying neurogenic change in muscle.

PMID- 21737345
TI  - Spatial variations in airborne microorganism and endotoxin concentrations at
      green waste composting facilities.
AB  - The emission and dispersal of bioaerosols from open-air commercial composting
      facilities continues to be contentious. A meta-dataset enumerating cultivable
      microorganism emission and downwind concentrations is not yet available. A
      dataset derived from repeated and replicated field studies over a period of two
      years at two commercial composting facilities is presented. The data
      characterises patterns in Aspergillus fumigatus, actinomycetes, Gram-negative
      bacteria and endotoxin emission and downwind concentrations. For all bioaerosols,
      compost agitation activities had a significant impact on concentrations; levels
      were variable up to 600 m downwind from site. Bioaerosols declined rapidly from
      source and exhibited a secondary peak 100-150 m from site boundary. All
      bioaerosols were found downwind from site in elevated concentrations. Compared to
      those found 100 m upwind, levels were significantly higher at 180 m downwind for
      A. fumigatus; at 300-400 m for actinomycetes and Gram negative bacteria, and at
      100 m for endotoxins. Periodically, elevated concentrations could be found for
      all bioaerosols at distances further downwind. The evidence provided by this data
      set provides operators and regulators of facilities with reliable data to inform
      the location, risk assessment and bioaerosol sampling strategies of commercial
      composting facilities.

PMID- 21737346
TI  - Studying synaptic plasticity in the human brain and opportunities for drug
      discovery.
AB  - Synaptic plasticity is the ability of synaptic connections between neurons to be
      strengthened or weakened; a process that is central to the information processing
      within the brain and which plays a particularly important role in enabling higher
      cognitive processes [1,2]. Its role in disease is becoming increasingly clear
      across a wide spectrum of CNS disorders. Thus, for example, dysfunctional
      synaptic plasticity has been reported in neurodegenerative disorders such as
      Alzheimer's Disease (AD) as well as in schizophrenia and in a range of disorders
      associated with learning disabilities [3]. Moreover, maladaptive plasticity
      processes in response to specific external challenges are believed to underlie
      disorders such as addiction and post-traumatic stress disorder (PTSD). The
      molecular basis of normal and disease plasticity is rapidly being unravelled such
      that synaptic plasticity now provides a unique platform from which to launch the
      hunt for highly innovative drugs to treat CNS disease by either, firstly,
      rectifying identifiable abnormalities in these processes, or secondly, utilizing
      these processes as a vehicle to rectify, or bypass, other mechanisms underlying
      disease. In this respect, recent advances have been made in studying synaptic
      plasticity in humans at the molecular through to clinical level and these
      approaches now provide a real opportunity to test synaptic plasticity as a
      treatment paradigm for a wide variety of CNS disorders.

PMID- 21737347
TI  - Targeting Plasmodium liver stages: better late than never.
AB  - The worldwide burden of malaria can be substantially reduced using existing
      public health interventions. However, elimination of Plasmodium will require
      fundamentally different approaches. Novel experimental attenuation strategies for
      active immunization using knockout strains have recently stimulated renewed
      interest in whole-parasite vaccine approaches. Preventive drug administration
      during transmission of wild-type sporozoites is a complementary strategy for
      eliciting protective immune responses. These whole-cell immunization strategies
      are based on one fundamental principle: inducing protection by blocking parasite
      conversion from the clinically silent liver phase to the pathogenic intra
      erythrocytic replication cycle. Here, we review the basis, evidence and targets
      for whole-cell-based vaccination strategies against the liver stage bottleneck in
      Plasmodium infections and discuss preclinical and clinical research
      opportunities.

PMID- 21737348
TI  - Gene expression in Trypanosoma brucei: lessons from high-throughput RNA
      sequencing.
AB  - Trypanosoma brucei undergoes major biochemical and morphological changes during
      its development from the bloodstream form in the mammalian host to the procyclic
      form in the midgut of its insect host. The underlying regulation of gene
      expression, however, is poorly understood. More than 60% of the predicted genes
      remain annotated as hypothetical, and the 5' and 3' untranslated regions
      important for regulation of gene expression are unknown for >90% of the genes. In
      this review, we compare the data from four recently published high-throughput RNA
      sequencing studies in light of the different experimental setups and discuss how
      these data can enhance genome annotation and give insights into the regulation of
      gene expression in T. brucei.

PMID- 21737349
TI  - Increased Foxp3 expression in guinea pigs infected with W-Beijing strains of M.
      tuberculosis.
AB  - There is increasing evidence that clinical isolates of Mycobacterium tuberculosis
      that belong to the W-Beijing genotype of newly emerging strains are often of very
      high virulence when tested in small animal models, including the mouse and guinea
      pig. In this report we provide further evidence to support this contention, and
      show that two W-Beijing strains are of very high virulence when introduced by low
      dose aerosol into outbred guinea pigs. In addition to severe lung pathology, each
      of these infections was associated with large influxes of activated CD4 and CD8 T
      cells into the lungs. Large influxes of macrophages were also observed, but the
      fraction of these showing evidence of activation by Class-II expression was
      relatively low. A progressive increase in neutrophils was also seen, with highest
      levels accumulating in the lungs of the W-Beijing infected animals. In the case
      of these two infections mRNA levels for TH1 cytokines was elevated early, but
      these then declined, and were replaced by increasing levels of message encoding
      for Foxp3, IL-10, and TGFbeta. These observations support the hypothesis that W
      Beijing strains are potent inducers of regulatory T cells, and that this event
      may enhance survival and transmission of these bacilli.

PMID- 21737350
TI  - Biosketch: Jerard Seghatchian.

PMID- 21737351
TI  - The science committee of the CCNAP: Eager to start.

PMID- 21737352
TI  - Development and validation of a quantitative food frequency questionnaire among
      rural- and urban-dwelling adults in Colombia.
AB  - OBJECTIVE: To validate a food frequency questionnaire (FFQ) against multiple 24
      hour dietary recalls (DRs) that could be used for Colombian adults. METHODS: A
      convenience sample of 219 individuals participated in the study. The validity of
      the FFQ was evaluated against multiple DRs. Four dietary recalls were collected
      during the year, and an FFQ was administered at the end of the study along with
      the fourth DR. RESULTS: Deattenuated correlation coefficient for FFQ against mean
      intake of 4 DRs varied from 0.77 for carbohydrate, 0.55 for energy, and 0.51 for
      protein. In rural areas, lower correlations were observed. The overall extent of
      agreement in each quartile of estimated nutrient intake varied from 61% to 83%.
      CONCLUSIONS AND IMPLICATIONS: The FFQ provides moderate to high estimates for
      energy and nutrient intake and can be employed to rank individuals based on their
      habitual intake.

PMID- 21737353
TI  - Long term video/EEG prevents unnecessary vagus nerve stimulator implantation in
      patients with psychogenic nonepileptic seizures.
AB  - OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are common paroxysmal events
      that mimic and can often be misdiagnosed as epileptic seizures. PNES account for
      10 to 40% of patients referred to epilepsy centers. Patients with uncontrolled
      PNES are at times subjected to vagus nerve stimulator (VNS) implantation. We
      report a series of such referred patients studied with video/EEG monitoring at
      our institution. METHODS: We evaluated patients who were implanted with a VNS by
      their primary neurologist for refractory seizures and who were referred to the
      Vanderbilt University epilepsy monitoring unit for a second opinion. The presumed
      diagnosis of epilepsy was based on abnormal routine EEG studies obtained by their
      primary neurologist. We evaluated these patients and recorded their typical
      spells between 2005 and 2009. We describe the results of 13 patients with VNS who
      were found to have PNES. The total number of patients with a VNS studied during
      this time was 60. RESULTS: None of the patients had undergone prior long-term
      video/EEG monitoring to document the nature of their events. A total of 13
      patients with an implanted VNS had exclusive PNES, 9 women and 4 men with a mean
      age of 38.2+/-10.4 years. Mean age at seizure onset was 28.5+/-15.4 years.
      Patients were taking two to four antiepileptic medications in addition to VNS at
      the time of video/EEG monitoring. The average latency from the time of VNS
      implantation to the confirmatory diagnosis was 2.8 years. One to ten (median=3)
      of these patients' typical seizures were recorded during video/EEG monitoring.
      All patients were subsequently discharged off antiepileptic medications, and five
      of these patients were discharged home with the VNS turned off. CONCLUSION: A VNS
      may be implanted inappropriately in patients with PNES. As video/EEG monitoring
      may help in excluding the diagnosis of PNES and preventing unnecessary VNS
      implants, it should be a requirement before VNS implantation.

PMID- 21737354
TI  - Aromatase inhibitor versus tamoxifen in postmenopausal woman with advanced breast
      cancer: a literature-based meta-analysis.
AB  - Clinical trials have reported conflicting results as to whether Aromatase
      inhibitors (AIs) as first-line hormonal therapy improve outcome over tamoxifen in
      postmenopausal women with advanced breast cancer. We performed a meta-analysis
      comparing primary and secondary endpoints of AIs to tamoxifen as first-line
      hormonal therapy in postmenopausal women with advanced breast cancer. The event
      based odds ratio (OR) with 95% confidence interval (95% CI) were derived, and a
      test of heterogeneity was applied. Six eligible trials (2560 patients) were
      selected from 488 studies that initially were identified. A significant
      difference in favoring AIs over tamoxifen was observed in overall response rate
      (ORR; OR, 1.56; 95% CI, 1.17-2.07; P = .002) and clinical benefit (CB; OR, 1.70;
      95% CI, 1.24-2.33; P = .0009).Whereas the trend toward an improved overall
      survival (OS) rate was not significant (OR, 1.95; 95% CI, 0.88-4.30; P =
      .10).Toxicities did not differ significantly except vaginal bleeding (OR, 0.30;
      95% CI, 0.16-0.56; P = .0002) and thromboembolic event (OR, 0.47; 95% CI, 0.28
      0.77; P = .003). AIs appeared to be effective and feasible compared with
      tamoxifen as first-line hormonal therapy in postmenopausal women with advanced
      breast cancer. Further prospective, randomized, controlled trials will be
      necessary.

PMID- 21737355
TI  - Feasibility and safety of weekly sequential epirubicin-paclitaxel as adjuvant
      treatment for operable breast cancer patients older than 70 years.
AB  - BACKGROUND: There are currently no internationally agreed recommendations for the
      management of adjuvant chemotherapy in women aged >70 years with high-risk breast
      cancer. The purpose of this study was to assess the feasibility and the tolerance
      of adjuvant weekly sequential epirubicin-paclitaxel combination in this setting.
      PATIENTS AND METHODS: From 2005 to 2009, 59 women over 70 years of age with
      operable breast cancer and who required adjuvant chemotherapy were proposed
      weekly sequential epirubicin-paclitaxel chemotherapy schedule, and were
      prospectively registered. Compliance and treatment tolerance were studied. We
      also report preliminary results of disease-free survival (DFS) and overall
      survival (OS). RESULTS: Weekly sequential epirubicin-paclitaxel was well
      tolerated. No grade 4 adverse event occurred. No secondary malignancy was
      observed. Compliance with chemotherapy was good: 95% of patients received the six
      planned cycles. After a median follow-up of 24 months, median DFS and OS were not
      reached, there were only three relapses, and two cancer-related deaths were
      reported. CONCLUSION: This study conducted in patients over 70 years of age
      demonstrates the feasibility of weekly adjuvant chemotherapy including
      anthracyclines and taxanes in a sequential schedule. This regimen is safe in
      terms of hematologic, nonhematologic, and cardiac toxicities, and showed
      encouraging efficacy, justifying further studies in geriatric patients.

PMID- 21737356
TI  - Coccydynia secondary to a large pelvic tumor of anorectal origin.

PMID- 21737357
TI  - Experimental measurements and Monte Carlo simulations of dose perturbation around
      a nonradioactive brachytherapy seed due to 6- and 18-MV photons.
AB  - PURPOSE: Radioactive seeds used in permanent prostate brachytherapy are composed
      of high-Z metals and may exceed 100 in a patient. If supplemental external beam
      treatment is administered afterward, the seeds may cause substantial dose
      perturbation, which is being investigated in this article. METHODS AND MATERIALS:
      Film measurements using 6-MV beam were primarily carried out using Kodak XV2 film
      layered above and below a nonradioactive iodine-125 ((125)I) seed. Monte Carlo
      simulations were carried out using DOSXYZnrc. Other experimental comparisons
      looked at changing beam energy, depth, and field size, including two opposing
      fields' pair. Effect of multiple seeds spatially spaced 0.5cm vertically was also
      studied. RESULTS: For a single (125)I seed, on XV film, there is a localized dose
      enhancement of 6.3% upstream and -10.9% downstream. With two opposing fields, a
      cold spot around the seed of ~3% was noticed. Increasing beam energy and field
      size decreased the magnitude of this effect, whereas the effect was found to
      increase with the increasing Z of material. DOSXYZnrc and EBT-2 film verified
      maximum dose enhancement of +15% upstream and -20% downstream of the (125)I seed
      surface. CONCLUSIONS: In general, the dose perturbation because of the seeds was
      spatially limited to ~2mm upstream and ~5mm downstream to the incident beam.
      Similar to other heterogeneities, the seeds perturbation depends on incident beam
      energy, field size, and its Z. With multiple seeds spatially apart and multiple
      radiation fields routinely used in external beam radiotherapy, the cumulative
      effect may not result in clinically significant dose perturbation.

PMID- 21737358
TI  - Neuronal loss and abnormal BMP/Smad signaling in the myenteric plexus of diabetic
      rats.
AB  - Bone morphogenetic proteins (BMPs) are critical molecules during gut
      morphogenesis. However, little is known about their participation in the
      homeostasis of adult gut and their possible role in diseases. Gastrointestinal
      complications occur during diabetes with loss of enteric neurons. In this study,
      we investigated the possible involvement of BMPs signaling pathway in diabetic
      enteric neuropathy in an experimental model of diabetes in rats. The expression
      of BMPs, BMPs receptors and intracellular Smad effectors were assessed in control
      and diabetic smooth muscle layer of jejunum by immunofluorescence, Western blot
      and RT-PCR methods. Myenteric neurons and glial cells were measured by
      immunofluorescence using specific markers. In addition, cell apoptosis was
      evaluated by means of direct and indirect techniques. We demonstrated that
      diabetic ganglia displayed a significant decrease in ganglion size due to
      enhanced apoptosis and loss of peripherin. A decrease in glial fibrillary acidic
      protein (GFAP protein) was also observed in enteric glial cells. BMP-2 was down
      regulated in the myenteric plexus of diabetic rats at 3 and 9weeks. A loss of
      enteric neurons by apoptosis was correlated with an ectopic BMP-4, increased BMPR
      Ia and nuclear p-Smad1 expression in the myenteric plexus. Insulin-treatment
      prevented the intestinal alterations observed. These findings suggest that
      diabetes is associated with an abnormal BMP/Smad signaling expression in the
      myenteric ganglia that affects the homeostasis of the enteric plexus.

PMID- 21737359
TI  - Determination of azatadine in human plasma by liquid chromatography/tandem mass
      spectrometry.
AB  - A sensitive method using liquid chromatography with tandem mass spectrometric
      detection (LC-MS/MS) was developed and validated for the analysis of
      antihistamine drug azatadine in human plasma. Loratadine was used as internal
      standard (IS). Analytes were extracted from human plasma by liquid/liquid
      extraction using ethyl acetate. The organic phase was reduced to dryness under a
      stream of nitrogen at 30  degrees C and the residue was reconstituted with the
      mobile phase. 5 MUL of the resulting solution was injected onto the LC-MS/MS
      system. A 4.6 mm * 150 mm, I.D. 5 MUm, Agilent TC-C(18) column was used to
      perform the chromatographic analysis. The mobile phase consisted of ammonium
      formate buffer 0.010 M (adjusted to pH 4.3 with 1M formic acid)/acetonitrile
      (20:80, v/v) The chromatographic run time was 5 min per injection and flow rate
      was 0.6 mL/min. The retention time was 2.4 and 4.4 min for azatadine and IS,
      respectively. The tandem mass spectrometric detection mode was achieved with
      electrospray ionization (ESI) iron source and the multiple reaction monitoring
      (MRM) (291.3 -> 248.2m/z for azatadine, 383.3 -> 337.3m/z for IS) was operated in
      positive ion modes. The low limit of quantitation (LLOQ) was 0.05 ng/mL. The
      intra-day and inter-day precision of the quality control (QC) samples was 8.93
      11.57% relative standard deviation (RSD). The inter-day accuracy of the QC
      samples was 96.83-105.07% of the nominal values.

PMID- 21737360
TI  - A simple HPLC-UV method for the simultaneous quantification of gefitinib and
      erlotinib in human plasma.
AB  - Gefitinib and erlotinib are two oral tyrosine kinase inhibitors (TKI) approved
      for the treatment of advanced non-small cell lung cancer (NSCLC). Published
      methods for simultaneous analysis of erlotinib and gefitinib in plasma are
      exclusively based on mass spectrometry. The purpose of this study was to develop
      a simple and sensitive HPLC-UV method to simultaneously quantify these two TKI in
      plasma. Following liquid-liquid extraction, gefitinib, erlotinib and sorafenib
      (internal standard), were separated with gradient elution (on a C8+
      Satisfaction((r)) using a mobile phase of acetonitrile/20mM ammonium acetate pH
      4.5). Samples were eluted at a flow rate of 0.4 ml/min throughout the 15-min run.
      Dual UV wavelength mode was used, with gefitinib and erlotinib monitored at 331
      nm, and sorafenib at 249 nm. The calibration was linear in the range 20-1000
      ng/ml and 80-4000 ng/ml for gefitinib and erlotinib, respectively. Inter- and
      intra-day imprecision were less than 7.2% and 7.6% for gefitinib and erlotinib,
      respectively. This analytical method was successfully applied to assess the
      steady state plasma exposure to these TKI in NSCLC patients. This simple,
      sensitive, accurate and cost-effective method can be used in routine clinical
      practice to monitor gefitinib or erlotinib concentrations in plasma from NSCLC
      patients.

PMID- 21737361
TI  - Stable isotope dilution assay for liquid chromatography-tandem mass spectrometric
      determination of L-homoarginine in human plasma.
AB  - Nitric oxide (NO), the endogenous modulator of vascular tone and structure,
      originates from oxidation of L-arginine catalysed by NO synthase (NOS). The L
      arginine derivative L-homoarginine serves as an alternative NOS substrate
      releasing NO, competing with L-arginine for NOS, arginase, and arginine
      transport. In the present article we report a liquid chromatography-tandem mass
      spectrometric (LC-tandem MS) method for the determination of L-homoarginine in
      human plasma by stable-isotope dilution. L-[(13)C(6)]-Homoarginine was used as
      internal standard. This method provides high sample throughput of 25-MUl aliquots
      of plasma with an analysis time of 4 min using LC-tandem MS electrospray
      ionisation in the positive mode (ESI+). Specific transitions for L-homoarginine
      and L-[(13)C(6)]-homoarginine were m/z 245 -> m/z 211 and m/z 251 -> m/z 217,
      respectively. The mean intra- and interassay CVs were 7.4 +/- 4.5% (+/-SD) for
      0.1-50 MUmol/L and 7.5 +/- 2.0% for 2 and 5 MUmol/L, respectively. Applying this
      method, a mean plasma concentration of L-homoarginine of 2.5 +/- 1.0 MUmol/L was
      determined in 136 healthy humans.

PMID- 21737362
TI  - Application of hollow fiber liquid phase microextraction coupled with high
      performance liquid chromatography for the study of the osthole pharmacokinetics
      in cerebral ischemia hypoperfusion rat plasma.
AB  - A simple and solvent-minimized sample preparation technique based on two-phase
      hollow fiber liquid phase microextraction has been developed and used to quantify
      the osthole in cerebral ischemia reperfusion rat plasma following oral
      administration. The analysis was performed by reversed phase high performance
      liquid chromatography with fluorescence detection. Extraction conditions such as
      solvent identity, agitation rate, salt concentration, extraction time, and length
      of the hollow fiber were optimized. Under the optimized conditions, the linear
      range of osthole in rat plasma was 5-500 ng mL(-1) (r(2) = 0.9997). The limit of
      detection (LOD) was 2 ng mL(-1) (S/N = 3) with limit of quantification (LOQ)
      being 5 ng mL(-1). The validated method has been successfully applied for
      pharmacokinetic studies of osthole from cerebral ischemia reperfusion rat plasma
      after oral administration.

PMID- 21737363
TI  - Use of Marfey's reagent and analogs for chiral amino acid analysis: assessment
      and applications to natural products and biological systems.
AB  - The present paper describes an updated knowledge and status on Marfey's reagent
      (MR), 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDNP-L-Ala-NH(2)). The
      reagent is used for pre-column derivatization of amino acids followed by HPLC
      separation of the diastereomers so formed. Emphasis is put on the design and
      application of structural variants which are synthesized by introducing different
      (other than L-Ala-NH(2)) L- and D-amino acid amides and amino acids in the 1,5
      difluoro-2,4-dinitro benzene (DFDNB) moiety, as the chiral auxiliary. Advantages,
      disadvantages, the required precautions and suitability of the approach for the
      separation of multi component mixtures of DL-amino acids are assessed. Use of two
      dimensional (2D) techniques, in particular online HPLC in combination with
      various mass spectrometry techniques is discussed as well as methods designated
      'advanced Marfey's method' and 'C(3) Marfey's method'. Application of MR and its
      variants for the determination of the stereochemistry of protein and non-protein
      amino acids in bioactive natural products isolated from living organisms
      (bacteria including blue-green algae, filamentous fungi, plants, marine sponges,
      invertebrates and vertebrates), in physiological samples including human beings,
      and in biologically relevant synthetic peptides are presented. In an outlook
      future applications are envisaged.

PMID- 21737364
TI  - The effect of low birth weight on height, weight and behavioral outcomes in the
      medium-run.
AB  - A number of studies have documented negative long term effects of low birth
      weight. Yet, not much is known about the dynamics of the process leading to
      adverse health and educational outcomes in the long run. While previous studies
      focusing mainly on LBW effects on physical growth and cognitive outcomes have
      found effects of the same size at both school age and young adulthood, others
      have found a diminishing negative effect over time. The purpose of this paper was
      to bring new evidence to this issue by analyzing the medium run effects of low
      birth weight on child behavioral outcomes as well as physical growth at ages 6
      months, 3, 7 and 11 years using data from the Danish Longitudinal Survey of
      Children. Observing the same children at different points in time enabled us to
      chart the evolution of anthropometric and behavioral deficits among children born
      with low birth weight and helped understanding the nature and timing of
      interventions.

PMID- 21737365
TI  - [Capillary beta-hydroxybutyrate determination for monitoring diabetic
      ketoacidosis].
AB  - BACKGROUND AND OBJECTIVE: Diabetic ketoacidosis (DKA) is the most severe acute
      metabolic complication of type 1 diabetes mellitus. Insulin treatment is commonly
      guided by plasma glucose levels and changes in venous blood gases, while beta
      hydroxibutyrate (BHB) levels are rarely measured. The study objective was to
      evaluate the value of capillary BHB monitoring in the course and resolution of
      DKA. PATIENTS AND METHODS: Thirty patients with type 1 diabetes admitted for DKA
      were enrolled. A standard protocol including monitoring of blood glucose, venous
      blood gases, semiquantitative ketonuria, and capillary BHB was used. Patients
      were divided into three groups by time to DKA resolution (group 1:<24 h, group 2:
      24-48 h, group 3: >48 h), and BHB results were compared to all other biochemical
      measurements. RESULTS: Mean laboratory results upon admission were: blood glucose
      415 (standard deviation [SD] 106) mg/dL; bicarbonate 9.6 (SD 1.5) mmol/L; pH 7.13
      (SD 0.04); BHB 4.33 (SD 0.48) mmol/L, and ketonuria 3+ in 22 patients and 4+ in
      6. BHB correlated well with bicarbonate (r=-0.24139; P=0.0161) and pH (r=
      0.56419; P<0.0001). BHB normalized earlier than ketonuria in all cases (group 1:
      15.5 vs 18.8 hours P<0.05; group 2: 18.2 vs 23.5 hours P<0.01; group 3: 37.3 vs
      41.7 hours P<0.01). Ten percent of patients still had ketonuria when blood ketone
      levels were already normal (<0.5 mmol/L). CONCLUSION: BHB measurement is an easy,
      practical, and reliable monitoring method in DKA and may be used as a parameter
      to adjust insulin treatment.

PMID- 21737366
TI  - Importance of clinical variables in the diagnosis of MODY2 and MODY3.
AB  - AIMS: MODY (maturity onset diabetes of the young) is a group of well-defined
      diseases clinically characterised by onset before age 25 years that does not
      require insulin treatment (at least initially) to prevent the formation of ketone
      bodies and autosomal dominant inheritance. Despite the importance of accurate
      classification, it is not always simple to catalogue the diagnosis of a young
      patient with diabetes, and genetic studies are often improperly used. METHODS: We
      describe the clinical features of patients negative for MODY2 and MODY3 and
      compared them to patients positive for these subtypes. RESULTS: All patients with
      MODY3 had been diagnosed before age 25 years and required drug therapy for blood
      glucose control. MODY2 patients were diagnosed at the first laboratory workup
      either incidentally or as part of gestational diabetes screening. The clinical
      description of the 19 patients negative for MODY2 and MODY3 showed that only two
      patients presented a clinical picture consistent with MODY3 and one patient with
      MODY2. CONCLUSIONS: Clinical features can be used for early exclusion of a MODY2
      or MODY3 diagnosis and may reduce the need for genetic testing.

PMID- 21737367
TI  - Early effects of portal flow modulation after extended liver resection in rat.
AB  - INTRODUCTION: The incidence of small-for-size-liver-syndrome after liver
      transplantation and extended liver resection may be reduced by portal flow
      modulation. However, many aspects of the small-for-size-liver-syndrome
      pathogenesis are still unclear. In this experimental study we evaluated the early
      effects of portal flow modulation after 80% hepatic resection in rats. MATERIALS
      AND METHODS: Rats were randomised in: sham operation (G1), conventional hepatic
      resection (G2), splenectomy and hepatic resection (G3), splenic transposition
      followed by hepatic resection after three weeks (G4). Six hours after operation,
      oxygen saturation of hepatic vein blood, glutathione, and standard liver markers
      were measured from hepatic venous blood. Glutathione measurement and
      histopatological examination were performed in the remnant liver. RESULTS: Total
      bilirubin and liver glutathione did not show differences between groups.
      Aspartate aminotransferase and alanine aminotransferase significantly increased
      in G2-G4 groups. Blood glutathione and oxygen saturation of hepatic vein blood
      were lower in G2 than in other groups. A gradient of micro-vesicular degeneration
      was more severe in G2 compared with G3 and G4. Apoptosis, hemorrhagic necrosis,
      mitochondrial damage and leucocyte adhesion were evident in G2. CONCLUSION: The
      portal flow modulation induced by splenectomy or splenic transposition was
      effective in limiting early damage after extended liver resection.

PMID- 21737368
TI  - [Treatment of loculated parapneumonic empyema. Video assisted thoracoscopy or
      fibrinolytics?].
AB  - OBJECTIVE: There is no consensus regarding the ideal treatment of loculated
      parapneumonic empyema (PPE). The aim of this study is to compare the
      effectiveness of drainage plus urokinase (DF) with video-assisted thoracoscopy
      (VATS). MATERIAL AND METHODS: Retrospective review. Patients admitted with a PPE
      between January 2001 and July 2008. Loculated empyema was diagnosed by chest
      ultrasound and patients were treated with DF or VATS depending on the attending
      surgeon. Compared variables were: post-operative stay, total hospital stay, days
      of tube thoracostomy, post-operative fever and treatment failure. RESULTS: One
      hundred and twenty one patients were admitted with the diagnosis of PPE.
      Seventeen patients were excluded from analysis because of simple parapneumonic
      effusions. Of the 104 patients included in the study, 47 were treated with
      urokinase and 57 with videothoracoscopy. No statistically significant differences
      (P>.05) were found between the median values in the DF and VATS groups for
      hospital stay (median 12 vs 12 days) or post-operative stay (median 9 vs 9 days).
      There were differences in duration of tube thoracostomy (median DF group 5 days,
      VATS, 4 days, P<.05) and in the post-operative fever (median 3 vs 2 days,
      p<0,05).Twenty two per cent of children needed a second procedure (14 patients of
      DF and 9 of VATS group, P=.09). CONCLUSIONS: According to our experience, the
      results of DF and VATS for the treatment of loculated parapneumonic empyema are
      similar. Although there are no statistical differences, there seems to be a
      higher rate of failure, with the need of more procedures in the DF group. This
      difference does not affect the average total hospital stay.

PMID- 21737369
TI  - [Primary gallbladder polyps].

PMID- 21737370
TI  - Bisulfite genomic sequencing of DNA from dried blood spot microvolume samples.
AB  - DNA methylation is an important event in epigenetic changes in cells, and a
      fundamental regulator of gene transcription. Bisulfite genomic sequencing is a
      powerful technique used in studies of DNA methylation. However, the established
      procedures often require relatively large amounts of DNA. In everyday practice,
      samples submitted for analysis might contain very small amounts of poor quality
      material, as is often the case with forensic stain samples. In this study, we
      assess a modified, more efficient method of bisulfite genomic sequencing. Genomic
      DNA extracted from 3-mm dried blood spots using QIAamp micro kit was treated with
      sodium bisulfite (using EpiTect kit). Subsequent methylation-specific PCR (MSP)
      followed by DNA sequencing displayed the differentially methylated region of
      imprinted gene SNRPN. Our results show that this new combination of efficient DNA
      extraction and bisulfite treatment provides high quality conversion of
      unmethylated cytosine to uracil for bisulfite genomic sequencing analysis. This
      reliable method substantially improves the DNA methylation analysis of forensic
      stain samples.

PMID- 21737371
TI  - Benzo[a]pyrene reduces testosterone production in rat Leydig cells via a direct
      disturbance of testicular steroidogenic machinery.
AB  - BACKGROUND: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a
      ubiquitous environmental pollutant that is currently suspected of being an
      endocrine disruptor. The testis is an important target for PAHs, yet insufficient
      attention has been paid to their effects on steroidogenesis in Leydig cells.
      OBJECTIVE: We hypothesized that long-term exposure to low concentrations of B[a]P
      might disrupt testosterone production in Leydig cells via an alteration of
      steroidogenic proteins. RESULTS: Oral exposure to B[a]P reduced serum and
      intratesticular fluid testosterone levels in rats. However, we did not observe
      serious testicular atrophy or azoospermia, although spermatogonial apoptosis was
      significantly increased. Compared with control cells, Leydig cells primed with
      B[a]P in vivo produced less testosterone in response to human chorionic
      gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note,
      the reduction of testosterone levels was accompanied by decreased expression of
      steroidogenic acute regulatory protein (StAR) and 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD), as well as increased levels of cytochrome P450 side
      chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc
      expression after exposure to B[a]P appears to be associated with a compensatory
      mechanism for producing the maximum amount of pregnenolone with the minimum
      amount of transported cholesterol by StAR; the down-regulation of 3beta-HSD may
      occur because B[a]P can negatively target 3beta-HSD, which is required for
      testosterone production. CONCLUSIONS: B[a]P exposure can decrease epididymal
      sperm quality, possibly by disturbing testosterone levels, and StAR may be a
      major steroidogenic protein that is targeted by B[a]P or other PAHs.

PMID- 21737372
TI  - Prenatal exposure to phthalates and infant development at 6 months: prospective
      Mothers and Children's Environmental Health (MOCEH) study.
AB  - BACKGROUND: There are increasing concerns over adverse effects of prenatal
      phthalate exposure on the neurodevelopment of infants. OBJECTIVES: Our goal was
      to explore the association between prenatal di(2-ethylhexyl) phthalate and
      dibutyl phthalate exposure and the Mental and Psychomotor Developmental Indices
      (MDI and PDI, respectively) of the Bayley Scales of Infant Development at 6
      months, as part of the Mothers and Children's Environmental Health Study.
      METHODS: Between 2006 and 2009, 460 mother-infant pairs from Seoul, Cheonan, and
      Ulsan, Korea, participated. Prenatal mono(2-ethyl-5-hydroxyhexyl) phthalate
      (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate
      (MBP) were measured in one urine sample acquired from each mother during the
      third trimester of pregnancy. Associations with log-transformed creatinine
      corrected phthalate concentrations were estimated using linear regression models
      adjusted for potential confounders. RESULTS: MDI was inversely associated with
      the natural log concentrations (micrograms per gram creatinine) of MEHHP [beta = 
      0.97; confidence interval (CI), -1.85 to -0.08] and MEOHP (beta = -0.95; CI, 
      1.87 to -0.03), and PDI was inversely associated with MEHHP (beta = -1.20; CI, 
      2.33 to -0.08). In males, MDI was inversely associated with MEHHP (beta = -1.46;
      CI, -2.70 to -0.22), MEOHP (beta = -1.57; CI, -2.87 to -0.28), and MBP (beta = 
      0.93; CI, -1.82 to -0.05); PDI was inversely associated with MEHHP (beta = -2.36;
      CI, -3.94 to -0.79), MEOHP (beta = -2.05; CI, -3.71 to -0.39), and MBP (beta = 
      1.25; CI, -2.40 to -0.11). No significant linear associations were observed for
      females. CONCLUSIONS: The results suggest that prenatal exposure to phthalates
      may be inversely associated with the MDI and PDI of infants, particularly males,
      at 6 months.

PMID- 21737373
TI  - Treatment of psoriasis with recombinant human LFA3-antibody fusion protein: a
      multi-center, randomized, double-blind trial in a Chinese population.
AB  - To evaluate clinical efficacy and safety of injectable recombinant human LFA3
      antibody fusion protein (rhLFA3-IgFP), a multi-center, randomized, double-blind,
      double-dummy, parallel-controlled clinical trial was performed in 212 cases of
      moderate to severe psoriasis. Intramuscular injection of rhLFA3-IgFP (15 mg/week)
      and oral administration of blank dummy methotrexate at the dose of 7.5 mg/week
      was performed in the patients in the experimental group, and control patients
      were orally administered with methotrexate at the dose of 7.5 mg/week and
      intramuscularly injected with the blank dummy rhLFA3-IgFP (15 mg/week). PASI was
      determined prior to and at 2, 4, 6, 8, 12, 16, 20 weeks after the treatment. The
      efficacy evaluation was carried out on 192 patients, and no significant
      differences were found in PASI50, PASI75 & PASI90 between the two groups after
      twelve weeks' treatment (p>0.05). After discontinuation, PASI scores continued to
      decrease drastically in the experiment group, whereas they increased in the
      control group. At 8 weeks after discontinuation, PASI scores were decreased by
      62.32% (p<0.05) and 52.67% (p<0.05) in the experimental and control groups,
      respectively. No serious adverse reactions were observed. In conclusion, the
      results of our investigation demonstrated that rhLFA3-IgFP was an effective
      therapy for chronic plaque psoriasis with lasting action and low incidence of
      adverse reactions.

PMID- 21737374
TI  - Cardiovascular and metabolic risk profile in German patients with moderate and
      severe psoriasis: a case control study.
AB  - Patients with psoriasis have a higher risk of cardiovascular and metabolic
      comorbidities, attributable to lifestyle factors, but also to shared inflammatory
      pathways and genetic factors. To investigate the association between moderate and
      severe psoriasis and metabolic and cardiovascular comorbidities, 100 patients
      hospitalized at University Medical Centre Mannheim, Germany, for psoriasis
      treatment were compared to two age- and sex-matched control groups, the first
      comprising other hospitalized patients (HCG) and the second comprising healthy
      individuals from an industrial cohort study (ICG). Multivariate logistic
      regression analysis with stepwise inclusion of cardiovascular risk factors was
      performed. Patients with psoriasis had significantly increased prevalences of
      smoking, obesity, diabetes, insulin resistance, pro-atherogenic cholesterol
      profiles and myocardial infarction and significantly decreased cardioprotective
      adiponectin. Unexpectedly, regression models controlling for confounding factors
      predicted significantly decreased OR for elevated total cholesterol in psoriasis
      cases (vs HCG: OR=0.50, p=0.045; vs ICG: OR=0.26, p=0.006). In contrast, OR for
      pro-atherogenic cholesterol profiles with LDL/HDL >3 was markedly increased
      (OR=2.45, p=0.012 or OR=3.02, p=0.020). Moreover, participants with psoriasis had
      significantly increased OR for elevated CRP as compared to the ICG (5.25,
      p=0.001). Our findings underscore the importance of cardiovascular and metabolic
      risk screening for all patients with moderate and severe psoriasis, including
      young patients.

PMID- 21737375
TI  - Role of serum uric acid in conditioning the association of psoriasis with
      metabolic syndrome.

PMID- 21737376
TI  - Skin-healing activity and toxicological evaluation of a proteinase fraction from
      Carica candamarcensis.
AB  - Previous studies demonstrated that proteinases from latex of C. candamarcensis
      act as mitogens on fibroblast and epithelial cells and a subsequent report showed
      their protective, angiogenic and wound healing effects on gastric ulcers. In this
      study, we present evidence of skin healing activity by the group of proteinases
      known as P1G10. By using a hairless mouse model, we compared the healing effect
      following topical application of various concentrations of P1G10. The data
      confirm that healing actions take place between 0.1 and 1%, without adverse local
      irritation or systemic toxicological action after a prolonged period of use. The
      wound healing effect is unaltered when P1G10 is previously inhibited with
      iodoacetamide. The low permeation of the hydrosoluble formulation Polawax((r))
      supports the maintenance of the drug at the site of application. These results
      extend the healing properties of these groups of enzymes in situations of
      dermatological trauma and open the way to future clinical applications.

PMID- 21737377
TI  - Tinea faciei with anterior blepharitis due to Trichophyton mentagrophytes.

PMID- 21737378
TI  - Subcutaneous injection of isophane protamine biosynthetic human insulin induced
      psoriasis at the injection site.

PMID- 21737379
TI  - Actinic granuloma associated with erythema nodosum.

PMID- 21737380
TI  - [Cell cycle and molecular targets: CDK inhibition].
AB  - Protein phosphorylation is a fundamental post-translational modification. It
      regulates a large number of critical cellular processes (differentiation,
      division, proliferation, apoptosis). Cell division is a process including a
      series of phases by which a parent cell divides into two daughter cells. The
      cells enter these stages then progress within the cell division under an accurate
      control by many proteins. These proteins are activated by phosphorylation. Cyclin
      dependent kinases are responsible for this phosphorylation and therefore
      represent potential therapeutic targets especially in oncology.

PMID- 21737381
TI  - Impact of minimally invasive surgery in the spectrum of current achalasia
      treatment options.
AB  - Minimally invasive Heller myotomy has evolved the "gold standard" procedure for
      achalasia in the spectrum of current treatment options. The laparoscopic
      technique has proved superior to the thoracoscopic approach due to improved
      visualization of the esophagogastric junction. Operative controversies most
      recently include the length of the myotomy, especially of its fun-dic part, with
      respect to the balance between postoperative persistent dysphagia and development
      of gastroesophageal reflux, as well as the type of the added antireflux
      procedure. Peri-operative mortality should approach 0%, and favorable long-term
      results can be achieved in > 90%.

PMID- 21737382
TI  - Impact of perceptual ability and mental imagery training on simulated
      laparoscopic knot-tying in surgical novices using a Nissen fundoplication model.
AB  - BACKGROUND: Performing minimally invasive surgery requires training and visual
      spatial intelligence. The aim of our study was to examine the impact of visual
      spatial perception and additional mental training on the simulated laparoscopic
      knot-tying task performed by surgical novices. METHODS: A total of 40 medical
      students randomly assigned to two groups underwent two sessions of laparoscopic
      basic training on a VR simulator (SimSurgery(r), Oslo, Norway). The variables
      time and tip trajectory (total path length of the instrument tip trajectory) were
      used to assess the performance of the intracorporeal knot-tying task using a
      laparoscopic Nissen fundoplication model. The experimental group completed
      additional mental practice during the interval between the two training sessions.
      All performed a cube subtest of a standard intelligence test (I-S-T 2000 R) to
      evaluate visual-spatial ability. RESULTS: All participants achieved an
      improvement in time (t = 9.861; p < 0.001) and tip trajectory (t = 6.833; p <
      0.001) in the second training session. High scores on the visual-spatial test
      correlated with a faster performance (r = -0.557; p < 0.001) and more precise
      movements (r = -0.377; p = 0.016). Comparison of the two groups did not show any
      statistical significant differences in the parameters time and tip trajectory.
      CONCLUSIONS: Visual-spatial intelligence tested by a cube test correlated with
      simulated laparoscopic knot-tying skills in surgical novices. Additional mental
      practice did not improve the overall knot-tying performance. Further studies are
      therefore required to determine whether mental practice might be beneficial for
      experienced laparoscopic surgeons or for more complex tasks.

PMID- 21737383
TI  - Learning curve of laparoscopy-assisted gastrectomy using a standardized surgical
      technique and an established educational system.
AB  - BACKGROUND AND AIMS: The learning curve of a trainee for laparoscopy-assisted
      gastrectomy in a high volume center, in which an educational system and a
      standardized laparoscopic procedure are already established, remains unclear.
      MATERIAL AND METHODS: The early surgical outcomes of the patients of two trainees
      were investigated. Both trainees followed a training program where they performed
      at least 20 cases being the camera assistant, 20 cases being the first assistant,
      before performing the surgery as an operator. RESULTS: The average operation
      time, intraoperative bleeding, the number of retrieved lymph nodes, and morbidity
      rate were 240.2 min, 45.7 ml, 35.4, and 13.0%, respectively. There was no
      learning curve effect observed except with the operation time of one trainee.
      CONCLUSIONS: In a high volume center with an established educational system,
      trainees could perform laparoscopy-assisted gastrectomy safely, although there
      might be a -learning curve effect in operation time and the surgeries took longer
      operation time in trainee's initial cases.

PMID- 21737384
TI  - Surgical outcomes and prognostic factors for ampulla of Vater cancer.
AB  - BACKGROUND AND AIMS: The prognosis for patients with ampulla of Vater cancer is
      better than other periampullary cancers. The aim of the present study is to
      determine the clinicopathologic factors predictive of survival and recurrence in
      patients with ampulla of Vater cancer. MATERIAL AND METHODS: From 1991 to 2008,
      we identified and reviewed 78 patients with ampulla of Vater cancer
      retrospectively. Clinicopathologic factors possibly influencing survival and
      recurrence were statistically analyzed. RESULTS: Pancreaticoduodenectomy was
      performed in 68 patients and 2 patients underwent transduodenal ampullectomy.
      Hospital mortality was 2.6%. The 5-year survival rates following resection were
      59.9%. Univariate analysis for overall survival revealed that total bilirubin
      greater than 5 mg/dl, ulcerative tumors, differentiation, and pancreatic invasion
      were significant prognostic factors. Recurrence occurred in 31 patients.
      Univariate analysis for disease-free survival revealed that total bilirubin
      greater than 5mg/dl, preoperative biliary drainage, tumor differentiation, and
      stage were statistically significant. Multivariate analysis revealed that tumor
      differentiation was an independent prognostic factor for recurrence. The presence
      of lymph node metastasis did not affect overall survival significantly in this
      study. However, two or more metastatic lymph nodes significantly affect disease
      free survival. CONCLUSIONS: Pancreaticoduodenectomy is a safe surgical procedure
      with acceptable long-term survival for ampulla of Vater cancer.
      Pancreaticoduodenectomy with lymph node dissection might control lymph node
      spread and enhance survival outcome.

PMID- 21737385
TI  - Endoscopic snare resection followed by laser ablation in the treatment of large,
      sessile rectal adenomas.
AB  - BACKGROUND AND AIMS: Large sessile rectal adenomas can be difficult to eradicate,
      and different treatment modalities are available. The aim of this study was to
      evaluate outcome after endoscopic snare resection followed by Nd:YAG laser
      ablation. MATERIAL AND METHODS: Over a 10-year period 92 of 99 (93%) patients
      were registered prospectively and attended follow-up examinations with endoscopy
      and biopsies. RESULTS: Fifty-four (59%) men and 38 (41%) women were included; 67
      patients (73%) had high grade (severe) intraepithelial dysplasia or intramucosal
      neoplasia. The adenomas ranged from 2-9 cm (median 4 cm) in diameter, and were
      located 2-15 cm (median 5 cm) from the anal verge. A median of two (range 1-6)
      piecemeal snare resection sessions and a median of one (range 1-7) laser
      treatments were performed for each patient. Complete eradication was achieved in
      86 patients (93%). Over a median follow-up period of 26 months, 20/86 (23%)
      suffered local recurrence, eight of whom were given a second laser treatment
      without developing further recurrence. In five of eight frail patients considered
      unsuitable for more radical treatment, repeated laser treatment was effective in
      keeping the adenoma small and symptoms at a minimum. As a whole the treatment was
      successful in 74/92 (80%) and partially successful in 5/92 (5%) of the patients.
      CONCLUSIONS: Snare resection followed by laser ablation is safe and still has a
      place in the treatment of old, frail patients with large rectal adenomas.
      However, there is a risk of missing an infiltrating carcinoma, and other
      treatment options are preferable in fit patients.

PMID- 21737386
TI  - The outcome of reduction mammaplasty is affected more by psychosocial factors
      than by changes in breast dimensions.
AB  - BACKGROUND AND AIMS: Several randomised studies have proved the effects of breast
      reduction surgery. However, search for predictive factors has not been
      successful. Therefore we decided to analyse breast dimension changes and to see
      whether these, or patient characteristics or individual psychosocial factors have
      an effect on the outcome. MATERIAL AND METHODS: Twenty-nine patients were
      assessed at baseline and at six months follow-up. Outcome measures used were two
      health-related quality of life questionnaires, a breast-associated symptoms
      questionnaire, a pain-rating questionnaire, and a mood questionnaire. Detailed
      breast dimensions were recorded. Forward stepwise linear regression was applied
      to detect possible associations between outcome measure changes and breast
      dimensions or patient-related factors. RESULTS: Preoperatively anxious patients
      had more improvement in the quality of life index scores, but less improvement in
      the mental health scores when compared to patients not anxious. Patients with
      physically demanding work had more improvement in the quality of life index
      scores and a trend to less improvement in the mental health scores when compared
      to patients with physically less stressful work. Patients with no overweight had
      a trend to better improvement in self-esteem. CONCLUSIONS: The outcome of
      reduction mammaplasty is affected more by psychosocial factors than by changes in
      breast dimensions.

PMID- 21737387
TI  - Secondary healing versus midline closure and modified Bascom natal cleft lift for
      pilonidal sinus disease.
AB  - BACKGROUND AND AIMS: Pilonidal sinus disease is a common disease in young
      employed male adults. Ongoing discomfort usually indicates an operative
      intervention. The main drawback is however the complication of wound healing.
      Numerous techniques for surgical treatment have been proposed, which underlies
      the lack of a superior technique. MATERIAL AND METHODS: A retrospective study was
      performed on the medical notes of 62 patients operated for a pilonidal sinus
      between May 2005 and December 2006. Used techniques were: 'modified Bascom
      procedure', 'excision and primary closure' and 'excision with secondary wound
      healing'. Patients' characteristics, operative parameters and data on outcome
      were included. The primary endpoint was wound healing. RESULTS: Twenty-five
      patients underwent the modified Bascom procedure, 19 underwent surgical excision
      with primary midline closure and 18 underwent surgical excision with secondary
      wound healing. There were no demographical differences between the groups of
      patients. The modified Bascom technique showed a significantly reduced wound
      healing time (29 days) compared to primary closure (52 days, p < 0.01) and
      secondary healing (62 days, p < 0.01). The duration of this modified procedure
      was significantly longer (49, 33 and 24 minutes respectively, p < 0.01).
      CONCLUSIONS: Wound healing remains an important problem in the surgical treatment
      of pilonidal disease. Significant faster convalescence can be achieved using the
      modified Bascom procedure. Wide local excision as primary therapy should not be
      advocated.

PMID- 21737388
TI  - Impact of coronary artery bypass surgery on ischemic mitral regurgitation.
AB  - INTRODUCTION: To determine the course of ischemic mitral regurgitation (IMR)
      after coronary artery bypass grafting (CABG), and evaluate preoperative factors
      which predict the development of the severity of IMR after CABG. METHODS: Between
      1992-2005, 1995 patients underwent CABG and 170 of them had IMR. Data of 131
      patients were retrospectively analyzed and living patients (n = 112) had a
      clinical follow-up visit. The mean follow-up time was 6.5 years. RESULTS: At the
      time of CABG, 66% of the 131 cases analyzed had mild, 31% had moderate, and 3%
      had severe IMR. At the time of follow-up, 52% of patients had either no IMR or
      mild IMR, 27% had moderate IMR, 6% had severe IMR and 15% suffered from cardiac
      related death. During follow-up IMR grade reduced in 25% of study patients. None
      of the patient had re-operation due to the mitral regurgitation. Multivariate
      analysis showed that left ventricular ejection fraction (LVEF) was an independent
      predictor of good prognosis (O.R. 1.4, 95% C.I. 1.15-1.83/ 10% increase of LVEF,
      p = 0.02). CONCLUSION: Half of the patients, who have IMR at the time of CABG,
      have no IMR or only mild IMR postoperatively. Good LVEF adds to the probability
      that CABG only can reduce IMR.

PMID- 21737389
TI  - Management of cement vertebroplasty in the treatment of vertebral hemangioma.
AB  - BACKGROUND: The vertebral hemangiomas are benign vascular lesions occurring in
      spine. Although uncommon, symptomatic vertebral hemangiomas can be painful and
      can limit daily activities. A number of methods have been used in the treatment
      of symptomatic and aggressive vertebral hemangioma, but none of them is optimal.
      Treatment with cement vertebroplasty showed very good results. This study aims to
      illustrate the validity of the treatment with cement vertebroplasty in patients
      with painful vertebral hemangiomas. PATIENTS AND METHODS: From January 2000 to
      January 2007, 24 patients were treated by percutaneous vertebroplasty because of
      hemangioma: 16 thoracic, 8 lumbar. There were 11 males and 13 females. The
      average age at the time of surgery was 48 years. All the patients complained of a
      pain syndrome resistant to continuing medication. All patients underwent X-ray
      examination, CT-scan and MR of the involved level preoperatively. A unipedicular
      approach under fluoroscopic guidance has been performed in all patients. All
      procedures have been carried out under the local anesthesia. The mean follow-up
      was 5.8 years. RESULTS: In all the patients a successful outcome has been
      observed with a complete resolution of pain symptom. Extravertebral vascular
      cement leakage has been observed in 3 patients, without any clinical radicular
      syndrome onset due to the epidural diffusion. Clinical and radiological follow-up
      showed stability of the treatment and absence of pain in all patients.
      CONCLUSION: Percutaneous treatment with vertebroplasty for symptomatic vertebral
      hemangiomas is a valuable, less-invasive, and a quick method that allows a
      complete and enduring resolution of the painful vertebral symptoms without
      findings of the vertebral body's fracture.

PMID- 21737390
TI  - Fascial incision and adhesiolysis combined with radiofrequency microtenotomy in
      treatment of chronic midportion Achilles tendinopathy.
AB  - BACKGROUND AND AIMS: Achilles tendinopathy is a common problem that can cause
      disturbing symptoms in activities of daily living as well as prevent sports
      activities. The purpose of this study was to evaluate the effects of fascial
      incision and adhesiolysis combined with radiofrequency microtenotomy in treatment
      of chronic midportion Achilles tendinopathy. MATERIAL AND METHODS: Twenty-four
      patients were included in this study. The cases were studied retrospectively. The
      mean age of the patients was 54 years (range, 39 to 72) and there were 12 women
      and 12 men. A final evaluation was done at an average of 30 months (range, 18 to
      45) after surgery, including radiofrequency microtenotomy. RESULTS: In all cases
      the Nirschl Pain Phase Scale of Athletic Overuse Injuries score improved and the
      difference was statistically significant (p < 0.0001). The patients themselves
      rated the result excellent in 14 cases and good in 10 cases. CONCLUSION: Fascial
      incision and adhesiolysis combined with radiofrequency microtenotomy seems to be
      a useful alternative in treatment of chronic midportion Achilles tendinopathy in
      cases of unsuccessful non-operative treatment.

PMID- 21737391
TI  - In-hospital treated pediatric injuries are increasing in Finland--a population
      based study between 1997 and 2006.
AB  - BACKGROUND AND AIMS: Injuries are an important public health problem as well as
      the leading cause of death and disability among children. Our aim was to
      longitudinally explore the incidence of in-hospital treated traumas, their
      operative treatment and related mortality among pediatric patients in Finland.
      METHODS: The National Hospital Discharge Register and the Official Cause-of-Death
      Statistics data of in-hospital treated pediatric trauma patients between 1997 and
      2006 in Finland were evaluated for hospitalizations, treatment modality and
      mortality. RESULTS: Fractures (69%) and head injuries (28%) were the most common
      in-hospital treated traumas (477/100,000 persons/year). These were followed by
      injuries of intra-abdominal (1.4%), thoracic (1.2%) and urological organs (0.6%).
      Head traumas constituted 67% of injury-related deaths. During the ten-year follow
      up period, the annual incidence (per 100,000 persons) of head injuries decreased
      by 13.6% (152 in 1997 vs. 131 in 2006, p < 0.0001) mainly contributing to a 30%
      decrease in overall injury-related mortality incidence (from 5.7 in 1997 to 4.0
      in 2006, p = 0.0519). The overall trauma incidence, and incidence of fractures
      and abdominal injuries significantly increased by 5.0% (p < 0.0001), 13.5% (p <
      0.0001) and 37% (p < 0.05), respectively, while the incidence of thoracic and
      urological injuries remained unchanged. Up to 15% of spleen injuries lead to
      splenectomy. CONCLUSIONS: Although overall and head trauma-related mortality is
      decreasing, the increasing incidence of fractures and abdominal injuries has
      amplified the overall incidence of severe injuries among children in Finland. A
      significant number of unnecessary splenectomies are still performed among
      children.

PMID- 21737392
TI  - From Home To Operation (FHTO)--a new surgical admission centre: does the
      comprehensive initialisation of a new process harm surgery outcome?
AB  - BACKGROUND AND AIMS: FHTO - From Home To Operation is a same day admission -model
      developed at Finland Hyvinkaa Hospital from as early as year 2000. In September
      2006, a new FHTO centre was opened, through which surgical patients walk into the
      operation room. This article describes how an extensive FHTO process transition
      effects patients operation outcome. METHODS: The data was collected of all
      elective surgical patients between March and May in 2006 and in 2007, six months
      before and after the new FHTO centre was opened. Patient demographics and surgery
      outcome measurements were reported and analysed between the two study periods.
      One month postoperative follow-up was recorded. RESULTS: Overall 1206 patients
      were included, 592 in 2006 and 614 in 2007. Before the extensive process change
      in 2006 54% of patients were admitted through old limited FHTO unit, and 46%
      through surgical ward. Six months after FHTO centre opening in 2007 same figures
      were 90,5% and 9,5% respectively. The baseline statistics differed statistically
      in kidney failure, that increased in 2007. Two deaths were recorded during
      postoperative follow-up each year. CONCLUSIONS: FHTO process transition included
      different surgical specialities and did not have negative impact on surgery
      outcome. Preoperative process should be debated thoroughly in every public
      hospital. The preoperative process transition from preoperative hospital stay to
      same day admission through new centre can be accomplished without harming surgery
      outcome.

PMID- 21737393
TI  - [Genetic background and clinical features of hereditary diffuse gastric cancer].
AB  - With the development of the molecular biology more pathological condition have
      been identified (p53 mutation and breast cancer, Ret protooncogene point mutation
      and medullary thyroid cancer), which could lead to malignant disease. The recent
      advances in the molecular genetics lead to the recognition of the hereditary
      diffuse gastric cancer that inherited in a dominant autosomal manner with
      incomplete penetrance. About 25-30% of families fulfilling the criteria have
      germline mutation of the CDH1 gene coding the calcium-dependent E-cadherin
      protein. In confirmed cases, prophylactic gastrectomy suggested in the early
      adolescent age.

PMID- 21737395
TI  - Reductive evolution of bacterial genome in insect gut environment.
AB  - Obligate endocellular symbiotic bacteria of insects and other organisms generally
      exhibit drastic genome reduction. Recently, it was shown that symbiotic gut
      bacteria of some stinkbugs also have remarkably reduced genomes. Here, we report
      the complete genome sequence of such a gut bacterium Ishikawaella capsulata of
      the plataspid stinkbug Megacopta punctatissima. Gene repertoire and evolutionary
      patterns, including AT richness and elevated evolutionary rate, of the 745,590 bp
      genome were strikingly similar to those of obligate gamma-proteobacterial
      endocellular insect symbionts like Buchnera in aphids and Wigglesworthia in
      tsetse flies. Ishikawaella was suggested to supply essential amino acids for the
      plant-sucking stinkbug as Buchnera does for the host aphid. Although Buchnera is
      phylogenetically closer to Wigglesworthia than to Ishikawaella, in terms of gene
      repertoire Buchnera was similar to Ishikawaella rather than to Wigglesworthia,
      providing a possible case of genome-level convergence of gene content. Meanwhile,
      several notable differences were identified between the genomes of Ishikawaella
      and Buchnera, including retention of TCA cycle genes and lack of flagellum
      related genes in Ishikawaella, which may reflect their adaptation to distinct
      symbiotic habitats. Unexpectedly, Ishikawaella retained fewer genes related to
      cell wall synthesis and lipid metabolism than many endocellular insect symbionts.
      The plasmid of Ishikawaella encoded genes for arginine metabolism and oxalate
      detoxification, suggesting the possibility of additional Ishikawaella roles
      similar to those of human gut bacteria. Our data highlight strikingly similar
      evolutionary patterns that are shared between the extracellular and endocellular
      insect symbiont genomes.

PMID- 21737396
TI  - Coexpression of linked gene pairs persists long after their separation.
AB  - In many eukaryotes, physically linked gene pairs tend to be coexpressed. However,
      it is still controversial to what extent this neighbor coexpression is maintained
      by selection and to what extent it is nonselective, purely mechanistic "leaky
      expression." Here, we analyze expression patterns of gene pairs that have lost
      their linkage in the evolution of Saccharomyces cerevisiae since its last common
      ancestor with Kluyveromyces waltii or that were never linked in the S. cerevisiae
      lineage but became neighbors in a related yeast. We demonstrate that coexpression
      of many linked genes is retained long after their separation and is thus likely
      to be functionally important. In addition, unlinked gene pairs that recently
      became neighbors in other yeast species tend to be coexpressed in S. cerevisiae.
      This suggests that natural selection often favors chromosomal rearrangements in
      which coexpressed genes become neighbors. Contrary to previous suggestions,
      selectively favorable coexpression appears not to be restricted to bidirectional
      promoters.

PMID- 21737397
TI  - Poor vision, functioning, and depressive symptoms: a test of the activity
      restriction model.
AB  - PURPOSE: This study tested the applicability of the activity restriction model of
      depressed affect to the context of poor vision in late life. This model
      hypothesizes that late-life stressors contribute to poorer mental health not only
      directly but also indirectly by restricting routine everyday functioning. METHOD:
      We used data from a national probability-based sample of older adults (N = 1,178;
      M = 69.2 years, approximately 50% female). Vision was assessed both subjectively
      (via self-report) and objectively (via a visual acuity test). Respondents also
      reported on their levels of physical and driving limitations, feelings of social
      isolation, and symptoms of depression. RESULTS: Path analyses indicated a strong
      fit of the data to the activity restriction model for subjective vision. In
      addition to directly contributing to higher depressive symptomatology, subjective
      vision contributed to depressive symptoms indirectly by predicting more physical
      limitations and feelings of social isolation that, in turn, contributed to more
      symptoms of depression; driving limitations did not mediate the relationship
      between subjective vision and depressive symptomatology. Objective vision
      contributed significantly to physical and driving limitations but was unrelated
      to feelings of social isolation and depressive symptomatology.  IMPLICATIONS:
      Supporting the activity restriction model, poorer self-rated vision in late life
      contributes to lower mental health directly and also indirectly by restricting
      individuals' ability to carry out routine day-to-day physical activities and
      increasing their feelings of social isolation. Interventions for older adults
      with vision-related problems could focus on maintaining or enhancing their
      physical and social functioning in order to promote their adaptation to poor
      vision.

PMID- 21737398
TI  - Effects of the Program of All-inclusive Care for the Elderly on hospital use.
AB  - PURPOSE OF THE STUDY: This study evaluates the effects of the Program of All
      Inclusive Care for the Elderly (PACE) on hospital use. PACE's capitated financing
      creates incentives to reduce the use of costly services. Furthermore, its
      emphasis on preventative care and regular monitoring by provides a mechanism for
      reducing unnecessary hospital use while maintaining quality of care. DESIGN AND
      METHODS: This study builds on previous research by comparing hospital use by PACE
      enrollees with a comparison group of frail community-dwelling older adults
      selected through propensity score matching over a 2-year period. Outcomes are
      estimated using regression adjustment with the 2-part model. RESULTS: The results
      suggest that PACE effectively controls hospital use among community-dwelling
      frail elderly persons. PACE enrollees spent an estimated average of 0.2 days in
      the hospital per month alive compared with an estimated average of 0.8 days in
      the hospital per month alive by comparison subjects or an estimated PACE effect
      of 0.6 days in the hospital per month alive per enrollee. IMPLICATIONS:  These
      results have implications for long-term care policy and service delivery. PACE
      provides a model for reducing unnecessary hospitalizations and rehospitalization
      through effective care management. The benefits of reduced hospital use are
      savings that offset the cost of an expanded set of services while maintaining
      quality.

PMID- 21737399
TI  - Cu2+ triggers reversible aggregation of a disordered His-rich dehydrin MpDhn12
      from Musa paradisiaca.
AB  - Copper is an essential nutrient, but it is toxic in excess. Here, we cloned and
      characterized a His-rich low molecular weight dehydrin from Musa paradisiaca,
      MpDhn12. Analysis by circular dichroism (CD) spectra and a thermal stability
      assay showed that MpDhn12 is an intrinsically disordered protein, and immobilized
      metal affinity chromatography (IMAC) analysis revealed that MpDhn12 can bind
      Cu(2+) both in vitro and in vivo. Interestingly, MpDhn12 aggregated under excess
      Cu(2+) conditions, and the aggregation was reversible and impaired by histidine
      modification with diethylpyrocarbonate (DEPC), while the disordered structure of
      another dehydrin ERD14 (as a control) was not changed. Furthermore, MpDhn12 could
      complement the copper-sensitive phenotype of yeast mutant Deltasod1. These
      results together suggested that MpDhn12 may take part in buffering copper levels
      through chelation and formation of aggregates in excess Cu(2+) conditions. To the
      best of our knowledge, it is the first report that a dehydrin interchanged
      between disordered and aggregated state triggered by copper.

PMID- 21737400
TI  - Activation of matriptase zymogen.
AB  - Matriptase is a type II transmembrane serine protease expressed abundantly in the
      epithelial cells and keratinocyte. It plays a key role in the establishment and
      maintenance of epithelial integrity. Matriptase is considered to be at the most
      upstream in cellular protease cascade. Activation of its zymogen is the most
      critical step in regulation of downstream proteases activities and physiological
      functions. It has recently found that the exposure of matriptase-expressing
      epithelial cells and its homogenate to mildly acidic pH induces the rapid
      activation of matriptase zymogen. On the other hand, high ionic strength prevents
      this activation. The activation of the zymogen is thought to be triggered by the
      acidification and the lowering of ionic strength in cell-surface
      microenvironments.

PMID- 21737401
TI  - The role of political and welfare state characteristics in infant mortality: a
      comparative study in wealthy countries since the late 19th century.
AB  - BACKGROUND: A close examination of the literature suggests that the consistent
      relation between political and welfare state characteristics and infant mortality
      in the second half of the 20th century in wealthy countries may not be causal.
      METHODS: The evolution of infant mortality since the late 19th century was
      studied in 17 wealthy countries classified according to political traditions,
      family policy model and period of infant mortality transition. The relation of
      public health expenditure and income inequality to infant mortality from 1980 to
      2005 was also evaluated. RESULTS: The Social Democratic and Scandinavian
      countries, and those with the earliest transition in infant mortality, had the
      lowest infant mortality rates until the early 21st century, whereas the late
      democracies, the Southern European countries, and those in which the transition
      in infant mortality took place later, had the highest rates until the late 20th
      century. By the early 21st century, the differences in infant mortality were
      negligible. Three of the four Scandinavian countries were the first to achieve
      infant mortality transition, whereas the Southern European countries were the
      last. The relation between public health expenditure and infant mortality varied
      depending on the time period in which the analysis was made, and increased income
      inequality was associated with higher infant mortality. CONCLUSIONS: The relation
      between political and welfare state characteristics and infant mortality in
      previous studies probably reflects the historical moment in which the transition
      in infant mortality took place in each country. Methodological limitations do not
      allow inference of causality in the associations found between welfare state
      characteristics and infant mortality.

PMID- 21737402
TI  - A graphical method for assessing agreement with the mean between multiple
      observers using continuous measures.
AB  - BACKGROUND: Currently, we are not aware of a method to assess graphically on one
      simple plot agreement between more than two observers making continuous
      measurements on the same subjects. METHODS: We aimed to develop a simple
      graphical method to assess agreement between multiple observers using continuous
      measurements. The Bland-Altman graphical method for assessing agreement between
      two observers using continuous measures was modified and extended to accommodate
      multiple observers. Mathematical formulae are derived and real data examples used
      to illustrate the proposed method. RESULTS: The examples show that the proposed
      graphical method of assessing agreement provides clinically useful information.
      This information includes estimates of the limits of agreement with the mean and
      a visual means for determining these limits over the range of measurements. In a
      data example that included five readers' measurements of 40 lung lesions, the
      intra-class correlation (ICC) was 0.84 indicating readers can reliably measure
      the lesions. However, the estimated limits of agreement with the mean were -1.1
      to 1.1 cm implying that the readers' measurements can plausibly differ from the
      mean estimated tumour size by more than 1 cm. This is a clinically significant
      difference according to the study authors. In addition, a plot of the limits of
      agreement with the mean by mean tumour size shows heterogeneous agreement
      presumably due to the varying degrees of definition at the edge of the lesions.
      CONCLUSIONS: The proposed graphical method of assessing agreement can be used
      alongside other measures such as ICC for reporting on reproducibility in studies
      of multiple observers making continuous measurements.

PMID- 21737403
TI  - Risk factors and interventions with statistically significant tiny effects.
AB  - BACKGROUND: Large studies may identify postulated risk factors and interventions
      with very small effect sizes. We aimed to assess empirically a large number of
      statistically significant relative risks (RRs) of tiny magnitude and their
      interpretation by investigators. METHODS: RRs in the range between 0.95 and 1.05
      were identified in abstracts of articles of cohort studies; articles published in
      NEJM, JAMA or Lancet; and Cochrane reviews. For each eligible tiny effect and the
      respective study, we recorded information on study design, participants, risk
      factor/intervention, outcome, effect estimates, P-values and interpretation by
      study investigators. We also calculated the probability that each effect lies
      outside specific intervals around the null (RR interval 0.97-1.03, 0.95-1.05,
      0.90-1.10). RESULTS: We evaluated 51 eligible tiny effects (median sample size
      112 786 for risk factors and 36 021 for interventions). Most (37/51) appeared in
      articles published in 2006-10. The effects pertained to nutrition (n = 19),
      genetic and other biomarkers (n = 8), correlates of health care (n = 8) and
      diverse other topics (n = 16) of clinical or public health importance and mostly
      referred to major clinical outcomes. A total of 15 of the 51 effects were >80%
      likely to lie outside the RR interval 0.97-1.03, but only 8 were >40% likely to
      lie outside the RR interval 0.95-1.05 and none was >1.7% likely to lie outside
      the RR interval 0.90-1.10. The authors discussed at least one concern for 23
      effects (small magnitude n = 19, residual confounding n = 11, selection bias n =
      1). No concerns were expressed for 28 effects. CONCLUSIONS: Statistically
      significant tiny effects for risk factors and interventions of clinical or public
      health importance become more common in the literature. Cautious interpretation
      is warranted, since most of these effects could be eliminated with even minimal
      biases and their importance is uncertain.

PMID- 21737404
TI  - Does alleviating poverty affect mothers' depressive symptoms? A quasi
      experimental investigation of Mexico's Oportunidades programme.
AB  - BACKGROUND: Depression is a major cause of disability, particularly among women;
      poverty heightens the risk for depression. Beyond its direct effects, maternal
      depression can harm children's health and development. This study aimed to assess
      the effects of a large-scale anti-poverty programme in Mexico (Oportunidades) on
      maternal depressive symptoms. METHODS: In 2003, 5050 women living in rural
      communities who had participated in Oportunidades since its inception were
      assessed and compared with a group of 1293 women from matched communities, whose
      families had received no exposure to Oportunidades at the time of assessment but
      were later enrolled. Self-reported depressive symptoms were measured using the
      Center for Epidemiologic Studies Depression Scale (CES-D). Ordinary least squares
      regressions were used to evaluate the treatment effect of programme participation
      on depression while adjusting for covariates and clustering at the community
      level. RESULTS: Women in the treatment group had lower depressive symptoms than
      those in the comparison group (unadjusted mean CES-D scores: 16.9 +/- 9.8 vs 18.6
      +/- 10.2). In multivariable analyses, programme participation was associated with
      lower depression whilst controlling for maternal age, education and household
      demographic, ethnicity and socio-economic variables [beta= -1.7 points, 95%
      confidence interval (95% CI) -2.46 to -0.96, P < 0.001]. Reductions in perceived
      stress and increases in perceived control were mediators of programme effects on
      women. CONCLUSIONS: Although Oportunidades did not target maternal mental health
      directly, we found modest but clinically meaningful effects on depressive
      symptoms. Our design permits stronger causal inference than observational studies
      that have linked poverty and depressive symptoms. Our results emphasize that the
      well-being of individuals is responsive to macro-level economic policies and
      programmes.

PMID- 21737405
TI  - Cohort profile: residential and non-residential environments, individual activity
      spaces and cardiovascular risk factors and diseases--the RECORD Cohort Study.

PMID- 21737406
TI  - Psychometric evaluation of a proposed Alzheimer's aggression scale.
AB  - The purpose of this study was to evaluate a popular measure of Alzheimer's
      disease (AD) memory and behavior problems and to determine whether its aggressive
      behavior items coalesced empirically as a subscale to form a psychometrically
      viable AD aggression measure for clinicians. Data from self-report questionnaires
      were examined from 419 informal AD caregivers in the southern United States.
      Principal axis factoring revealed a unidimensional solution with robust item
      loadings on the single factor. Three forms of reliability analysis indicated
      moderately strong internal consistency on this proposed measure. Evidence of
      convergent validity analysis was suggested via the measure's significant
      correlations to theoretically linked constructs. The proposed measure emerged as
      a reliable and valid tool for health care practitioners for the appraisal of
      problematic AD aggression behaviors from the caregiver perspective.

PMID- 21737407
TI  - A qualitative study of family involvement in decisions about life support in the
      intensive care unit.
AB  - We explored family involvement in decisions about life support interventions in
      the intensive care unit study using a critical incident technique to focus on
      specific case exemplars contributed by participants. A total of 6 family members
      and 9 health care professionals were interviewed. Participants described 2
      options (life support or comfort care) and values associated with options:
      maintaining quality of life, surviving critical illness, minimizing pain and
      suffering, not being attached to machines, needing adjustment time, and judicious
      health care resource use. Barriers to involvement included not being offered
      alternative options; no specific trigger to initiate decision making; dominant
      influence of professionals' values; and families lacking understandable
      information. Family members are unlikely to engage in decision making unless
      professionals identify the decision and address other barriers to family
      involvement.

PMID- 21737409
TI  - Menthol should not be given a free pass based on studies of biomarkers of
      toxicity.
AB  - Exposure and toxicity studies comparing menthol and nonmenthol cigarettes have
      resulted in mixed results. On the basis of those results, cigarette manufacturers
      have concluded that there is no increased harm from the addition of menthol to
      cigarettes. We propose that such a narrow definition of harm is not appropriate
      in dealing with the issue of menthol, and its broader negative public health
      impact.

PMID- 21737410
TI  - State disparities in colorectal cancer mortality patterns in the United States.
AB  - BACKGROUND: Colorectal cancer (CRC) mortality rates have been decreasing for many
      decades in the United States, with the decrease accelerating in the most recent
      time period. The extent to which this decrease varies across states and its
      influence on the geographic patterns of rates is unknown. METHODS: We analyzed
      the temporal trend in age-standardized CRC death rates for each state from 1990
      to 2007 using joinpoint regression. We also examined the change in death rates
      between 1990-1994 and 2003-2007 using rate ratios with 95% confidence intervals
      and illustrated the change in pattern using maps. The relationship between the
      change in mortality rates and CRC screening rates for 2004 by state was examined
      using Pearson's correlation. RESULTS: CRC mortality rates significantly decreased
      in all states except Mississippi between 1990 and 2007 based on the joinpoint
      model. The decrease in death rates between 1990-1994 and 2003-2007 ranged from 9%
      in Alabama to greater than 33% in Massachusetts, Rhode Island, New York, and
      Alaska; Mississippi and Wyoming showed no significant decrease. Generally, the
      northeastern states showed the largest decreases, whereas southern states showed
      the smallest decreases. The highest CRC mortality rates shifted from the
      northeastern states during 1990 to 1994 to the southern states along the
      Appalachian corridor during 2003 to 2007. The decrease in CRC mortality rates by
      state correlated strongly with uptake of screening (r = -0.65, P < 0.0001).
      CONCLUSIONS: Progress in reducing CRC mortality varies across states, with the
      Northeast showing the most progress and the South showing the least progress.
      IMPACT: These findings highlight the need for wider dissemination of CRC
      screening.

PMID- 21737411
TI  - Validation of a light questionnaire with real-life photopic illuminance
      measurements: the Harvard Light Exposure Assessment questionnaire.
AB  - BACKGROUND: Shift work, which necessitates light exposure at night, is now
      considered a probable carcinogen. To study the effects of light on chronic
      diseases like cancer, methods to measure light exposure in large observational
      studies are needed. We aimed to investigate the validity of self-reported current
      light exposure. METHODS: We developed a self-administered semiquantitative light
      questionnaire, the Harvard Light Exposure Assessment (H-LEA) questionnaire, and
      compared photopic scores derived from this questionnaire with actual photopic and
      circadian measures obtained from a real-life 7-day light meter application among
      132 women (85 rotating night shift workers and 47 day workers) participating in
      the Nurses' Health Study II. RESULTS: After adjustment for age, body mass index
      (BMI), collection day, and night work status, the overall partial Spearman
      correlation between self-report of light exposure and actual photopic light
      measurements was 0.72 (P < 0.001; Kendall tau = 0.57) and 0.73 (P < 0.0001;
      Kendall tau = 0.58) when correlating circadian light measurements. There were
      only minimal differences in accuracy of self-report of light exposure and
      photopic or "circadian" light measurement between day (r = 0.77 and 0.78,
      respectively) and rotating night shift workers (r = 0.68 and 0.69, respectively).
      CONCLUSIONS: The results of this study provide evidence of the criterion validity
      of self-reported light exposure using the H-LEA questionnaire. IMPACT: This
      questionnaire is a practical method of assessing light exposure in large-scale
      epidemiologic studies.

PMID- 21737412
TI  - FIT performance in early-stage colorectal cancer--letter.

PMID- 21737414
TI  - Developmental pattern of aquaporin expression in barley (Hordeum vulgare L.)
      leaves.
AB  - Aquaporins are multifunctional membrane channels which belong to the family of
      major intrinsic proteins (MIPs) and are best known for their ability to
      facilitate the movement of water. In the present study, earlier results from
      microarray experiments were followed up. These experiments had suggested that, in
      barley (Hordeum vulgare L.), aquaporin family members are expressed in distinct
      patterns during leaf development. Real-time PCR and in situ hybridization were
      used to analyse the level and tissue-distribution of expression of candidate
      aquaporins, focusing on plasma membrane and tonoplast intrinsic proteins (PIPs,
      TIPs). Water channel function of seven aquaporins, whose transcripts were the
      most abundant and the most variable, was tested through expression in yeast and,
      in part, through expression in oocytes. All PIP1 and PIP2 subfamily members
      changed in expression during leaf development, with expression being much higher
      or lower in growing compared with mature tissue. The same applied to those TIPs
      which were expressed at detectable levels. Specific roles during leaf development
      are proposed for particular aquaporins.

PMID- 21737415
TI  - Role of DREBs in regulation of abiotic stress responses in plants.
AB  - Abiotic stresses such as drought, high salinity, and cold are common adverse
      environmental conditions that significantly influence plant growth and
      productivity worldwide. The phytohormone abscisic acid (ABA) plays an important
      role in physiological and developmental responses as well as in co-ordinating
      various stress signal transduction pathways in plants. DREBs (dehydration
      responsive element binding) are important plant transcription factors (TFs) that
      regulate the expression of many stress-inducible genes mostly in an ABA
      independent manner and play a critical role in improving the abiotic stress
      tolerance of plants by interacting with a DRE/CRT cis-element present in the
      promoter region of various abiotic stress-responsive genes. This review
      summarizes recent studies highlighting the role of the DRE-binding family of TFs
      in the adaptive responses to different abiotic stresses and their structural and
      functional characters with emphasis on the expression and regulation of DREBs.
      The practical and application value of DREBs in crop improvement, such as stress
      tolerance engineering as well as marker-assisted selection (MAS), has also been
      discussed.

PMID- 21737416
TI  - Targeting genes in living mammals by RNA interference.
AB  - More than a decade has passed since the discovery of RNA interference (RNAi), an
      eukaryotic sequence-specific degradation of mRNA induced by complementary double
      stranded RNA (dsRNA). RNAi became a common tool for controlled down-regulation of
      gene expression in cultured cells, as well as in various model organisms. This
      review summarizes RNAi-based tools for silencing genes in living mammals, which
      include: (i) transgenic RNAi strategies, where RNAi is triggered by a transgene
      transmitted through the germline and (ii) approaches, where an RNAi trigger is
      delivered into an adult animal.

PMID- 21737417
TI  - Introduction of fruits and vegetables into children's diets in the Iringa Region,
      Tanzania.

PMID- 21737418
TI  - L-DOPA-induced dyskinesia is associated with regional increase of striatal
      dynorphin peptides as elucidated by imaging mass spectrometry.
AB  - Opioid peptides are involved in various pathophysiological processes, including
      algesia, epilepsy, and drug dependence. A strong association between L-DOPA
      induced dyskinesia (LID) and elevated prodynorphin mRNA levels has been
      established in both patients and in animal models of Parkinson's disease, but to
      date the endogenous prodynorphin peptide products have not been determined. Here,
      matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry
      (IMS) was used for characterization, localization, and relative quantification of
      striatal neuropeptides in a rat model of LID in Parkinson's disease. MALDI IMS
      has the unique advantage of high sensitivity and high molecular specificity,
      allowing comprehensive detection of multiple molecular species in a single tissue
      section. Indeed, several dynorphins and enkephalins could be detected in the
      present study, including dynorphin A(1-8), dynorphin B, alpha-neoendorphin,
      MetEnkRF, MetEnkRGL, PEnk (198-209, 219-229). IMS analysis revealed elevated
      levels of dynorphin B, alpha-neoendorphin, substance P, and PEnk (220-229) in the
      dorsolateral striatum of high-dyskinetic animals compared with low-dyskinetic and
      lesion-only control rats. Furthermore, the peak-intensities of the prodynorphin
      derived peptides, dynorphin B and alpha-neoendorphin, were strongly and
      positively correlated with LID severity. Interestingly, these LID associated
      dynorphin peptides are not those with high affinity to kappa opioid receptors,
      but are known to bind and activate also MU- and Delta-opioid receptors. In
      addition, the peak intensities of a novel endogenous metabolite of alpha
      neoendorphin lacking the N-terminal tyrosine correlated positively with
      dyskinesia severity. MALDI IMS of striatal sections from Pdyn knockout mice
      verified the identity of fully processed dynorphin peptides and the presence of
      endogenous des-tyrosine alpha-neoendorphin. Des-tyrosine dynorphins display
      reduced opioid receptor binding and this points to possible novel nonopioid
      receptor mediated changes in the striatum of dyskinetic rats. Because des
      tyrosine dynorphins can only be detected by mass spectrometry, as no antibodies
      are available, these findings highlight the importance of MALDI IMS analysis for
      the study of molecular dynamics in neurological diseases.

PMID- 21737419
TI  - Calculating transcription factor binding maps for chromatin.
AB  - Current high-throughput experiments already generate enough data for retrieving
      the DNA sequence-dependent binding affinities of transcription factors (TF) and
      other chromosomal proteins throughout the complete genome. However, the reverse
      task of calculating binding maps in a chromatin context for a given set of
      concentrations and TF affinities appears to be even more challenging and
      computationally demanding. The problem can be addressed by considering the DNA
      sequence as a one-dimensional lattice with units of one or more base pairs. To
      calculate protein occupancies in chromatin, one needs to consider the competition
      of TF and histone octamers for binding sites as well as the partial unwrapping of
      nucleosomal DNA. Here, we consider five different classes of algorithms to
      compute binding maps that include the binary variable, combinatorial, sequence
      generating function, transfer matrix and dynamic programming approaches. The
      calculation time of the binary variable algorithm scales exponentially with DNA
      length, which limits its use to the analysis of very small genomic regions. For
      regulatory regions with many overlapping binding sites, potentially applicable
      algorithms reduce either to the transfer matrix or dynamic programming approach.
      In addition to the recently proposed transfer matrix formalism for TF access to
      the nucleosomal organized DNA, we develop here a dynamic programming algorithm
      that accounts for this feature. In the absence of nucleosomes, dynamic
      programming outperforms the transfer matrix approach, but the latter is faster
      when nucleosome unwrapping has to be considered. Strategies are discussed that
      could further facilitate calculations to allow computing genome-wide TF binding
      maps.

PMID- 21737420
TI  - Conceptual framework and pilot study to benchmark phylogenomic databases based on
      reference gene trees.
AB  - Phylogenomic databases provide orthology predictions for species with fully
      sequenced genomes. Although the goal seems well-defined, the content of these
      databases differs greatly. Seven ortholog databases (Ensembl Compara, eggNOG,
      HOGENOM, InParanoid, OMA, OrthoDB, Panther) were compared on the basis of
      reference trees. For three well-conserved protein families, we observed a
      generally high specificity of orthology assignments for these databases. We show
      that differences in the completeness of predicted gene relationships and in the
      phylogenetic information are, for the great majority, not due to the methods
      used, but to differences in the underlying database concepts. According to our
      metrics, none of the databases provides a fully correct and comprehensive protein
      classification. Our results provide a framework for meaningful and systematic
      comparisons of phylogenomic databases. In the future, a sustainable set of 'Gold
      standard' phylogenetic trees could provide a robust method for phylogenomic
      databases to assess their current quality status, measure changes following new
      database releases and diagnose improvements subsequent to an upgrade of the
      analysis procedure.

PMID- 21737421
TI  - Transient vision loss in a patient with severe metformin-associated lactic
      acidosis.

PMID- 21737422
TI  - Enhanced translation by Nucleolin via G-rich elements in coding and non-coding
      regions of target mRNAs.
AB  - RNA-binding proteins (RBPs) regulate gene expression at many post-transcriptional
      levels, including mRNA stability and translation. The RBP nucleolin, with four
      RNA-recognition motifs, has been implicated in cell proliferation, carcinogenesis
      and viral infection. However, the subset of nucleolin target mRNAs and the
      influence of nucleolin on their expression had not been studied at a
      transcriptome-wide level. Here, we globally identified nucleolin target
      transcripts, many of which encoded cell growth- and cancer-related proteins, and
      used them to find a signature motif on nucleolin target mRNAs. Surprisingly, this
      motif was very rich in G residues and was not only found in the 3'-untranslated
      region (UTR), but also in the coding region (CR) and 5'-UTR. Nucleolin enhanced
      the translation of mRNAs bearing the G-rich motif, since silencing nucleolin did
      not change target mRNA stability, but decreased the size of polysomes forming on
      target transcripts and lowered the abundance of the encoded proteins. In summary,
      nucleolin binds G-rich sequences in the CR and UTRs of target mRNAs, many of
      which encode cancer proteins, and enhances their translation.

PMID- 21737423
TI  - Functionally important structural elements of U12 snRNA.
AB  - U12 snRNA is analogous to U2 snRNA of the U2-dependent spliceosome and is
      essential for the splicing of U12-dependent introns in metazoan cells. The
      essential region of U12 snRNA, which base pairs to the branch site of minor class
      introns is well characterized. However, other regions which are outside of the
      branch site base pairing region are not yet characterized and the requirement of
      these structures in U12-dependent splicing is not clear. U12 snRNA is predicted
      to form an intricate secondary structure containing several stem-loops and single
      stranded regions. Using a previously characterized branch site genetic
      suppression assay, we generated second-site mutations in the suppressor U12 snRNA
      to investigate the in vivo requirement of structural elements in U12-dependent
      splicing. Our results show that stem-loop IIa is essential and required for in
      vivo splicing. Interestingly, an evolutionarily conserved stem-loop IIb is
      dispensable for splicing. We also show that stem-loop III, which binds to a p65
      RNA binding protein of the U11-U12 di.snRNP complex, is essential for in vivo
      splicing. The data validate the existence of proposed stem-loops of U12 snRNA and
      provide experimental support for individual secondary structures.

PMID- 21737424
TI  - Towards computational specificity screening of DNA-binding proteins.
AB  - DNA-binding proteins are key players in the regulation of gene expression and,
      hence, are essential for cell function. Chimeric proteins composed of DNA-binding
      domains and DNA modifying domains allow for precise genome manipulation. A key
      prerequisite is the specific recognition of a particular nucleotide sequence.
      Here, we quantitatively assess the binding affinity of DNA-binding proteins by
      molecular dynamics-based alchemical free energy simulations. A computational
      framework was developed to automatically set up in silico screening assays and
      estimate free energy differences using two independent procedures, based on
      equilibrium and non-equlibrium transformation pathways. The influence of
      simulation times on the accuracy of both procedures is presented. The binding
      specificity of a zinc-finger transcription factor to several sequences is
      calculated, and agreement with experimental data is shown. Finally we propose an
      in silico screening strategy aiming at the derivation of full specificity
      profiles for DNA-binding proteins.

PMID- 21737425
TI  - XRCC1 haploinsufficiency in mice has little effect on aging, but adversely
      modifies exposure-dependent susceptibility.
AB  - Oxidative DNA damage plays a role in disease development and the aging process. A
      prominent participant in orchestrating the repair of oxidative DNA damage,
      particularly single-strand breaks, is the scaffold protein XRCC1. A series of
      chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice
      were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median
      lifespan of ~26 months and a nearly identical maximal life expectancy of ~37
      months. However, a number of HZ animals (7 of 92) showed a propensity for
      abdominal organ rupture, which may stem from developmental abnormalities given
      the prominent role of XRCC1 in endoderm and mesoderm formation. For other end
      points evaluated-weight, fat composition, blood chemistries, condition of major
      organs, tissues and relevant cell types, behavior, brain volume and function, and
      chromosome and telomere integrity-HZ mice exhibited by-and-large a normal
      phenotype. Treatment of animals with the alkylating agent azoxymethane resulted
      in both liver toxicity and an increased incidence of precancerous lesions in the
      colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals
      has little effect on chronological longevity and many key biological markers of
      aging in the absence of environmental challenges, but may adversely affect normal
      animal development or increase disease susceptibility to a relevant genotoxic
      exposure.

PMID- 21737426
TI  - Whole-transcriptome RNAseq analysis from minute amount of total RNA.
AB  - RNA sequencing approaches to transcriptome analysis require a large amount of
      input total RNA to yield sufficient mRNA using either poly-A selection or
      depletion of rRNA. This feature makes it difficult to miniaturize transcriptome
      analysis for greater efficiency. To address this challenge, we devised and
      validated a simple procedure for the preparation of whole-transcriptome cDNA
      libraries from a minute amount (500 pg) of total RNA. We compared a single-sample
      library prepared by this Ovation RNA-Seq system with two available methods of
      mRNA enrichment (TruSeq poly-A enrichment and RiboMinus rRNA depletion). Using
      the Ovation preparation method for a set of eight mouse tissue samples, the RNA
      sequencing data obtained from two different next-generation sequencing platforms
      (SOLiD and Illumina Genome Analyzer IIx) yielded negligible rRNA reads (<3.5%)
      while retaining transcriptome sequencing fidelity. We further validated the
      Ovation amplification technique by examining the resulting library complexity,
      reproducibility, evenness of transcript coverage, 5' and 3' bias and platform
      specific biases. Notably, in this side-by-side comparison, SOLiD sequencing
      chemistry is biased toward higher GC content of transcriptome and Illumina Genome
      analyzer IIx is biased away from neutral to lower GC content of the
      transcriptomics regions.

PMID- 21737427
TI  - Native mass spectrometry provides direct evidence for DNA mismatch-induced
      regulation of asymmetric nucleotide binding in mismatch repair protein MutS.
AB  - The DNA mismatch repair protein MutS recognizes mispaired bases in DNA and
      initiates repair in an ATP-dependent manner. Understanding of the allosteric
      coupling between DNA mismatch recognition and two asymmetric nucleotide binding
      sites at opposing sides of the MutS dimer requires identification of the relevant
      MutS.mmDNA.nucleotide species. Here, we use native mass spectrometry to detect
      simultaneous DNA mismatch binding and asymmetric nucleotide binding to
      Escherichia coli MutS. To resolve the small differences between macromolecular
      species bound to different nucleotides, we developed a likelihood based algorithm
      capable to deconvolute the observed spectra into individual peaks. The obtained
      mass resolution resolves simultaneous binding of ADP and AMP.PNP to this ABC
      ATPase in the absence of DNA. Mismatched DNA regulates the asymmetry in the
      ATPase sites; we observe a stable DNA-bound state containing a single AMP.PNP
      cofactor. This is the first direct evidence for such a postulated mismatch repair
      intermediate, and showcases the potential of native MS analysis in detecting
      mechanistically relevant reaction intermediates.

PMID- 21737428
TI  - Synthetic RNA modules for fine-tuning gene expression levels in yeast by
      modulating RNase III activity.
AB  - The design of synthetic gene networks requires an extensive genetic toolbox to
      control the activities and levels of protein components to achieve desired
      cellular functions. Recently, a novel class of RNA-based control modules, which
      act through post-transcriptional processing of transcripts by directed RNase III
      (Rnt1p) cleavage, were shown to provide predictable control over gene expression
      and unique properties for manipulating biological networks. Here, we increase the
      regulatory range of the Rnt1p control elements, by modifying a critical region
      for enzyme binding to its hairpin substrates, the binding stability box (BSB). We
      used a high throughput, cell-based selection strategy to screen a BSB library for
      sequences that exhibit low fluorescence and thus high Rnt1p processing
      efficiencies. Sixteen unique BSBs were identified that cover a range of protein
      expression levels, due to the ability of the sequences to affect the hairpin
      cleavage rate and to form active cleavable complexes with Rnt1p. We further
      demonstrated that the activity of synthetic Rnt1p hairpins can be rationally
      programmed by combining the synthetic BSBs with a set of sequences located within
      a different region of the hairpin that directly modulate cleavage rates,
      providing a modular assembly strategy for this class of RNA-based control
      elements.

PMID- 21737429
TI  - PhenomeNET: a whole-phenome approach to disease gene discovery.
AB  - Phenotypes are investigated in model organisms to understand and reveal the
      molecular mechanisms underlying disease. Phenotype ontologies were developed to
      capture and compare phenotypes within the context of a single species. Recently,
      these ontologies were augmented with formal class definitions that may be
      utilized to integrate phenotypic data and enable the direct comparison of
      phenotypes between different species. We have developed a method to transform
      phenotype ontologies into a formal representation, combine phenotype ontologies
      with anatomy ontologies, and apply a measure of semantic similarity to construct
      the PhenomeNET cross-species phenotype network. We demonstrate that PhenomeNET
      can identify orthologous genes, genes involved in the same pathway and gene
      disease associations through the comparison of mutant phenotypes. We provide
      evidence that the Adam19 and Fgf15 genes in mice are involved in the tetralogy of
      Fallot, and, using zebrafish phenotypes, propose the hypothesis that the
      mammalian homologs of Cx36.7 and Nkx2.5 lie in a pathway controlling cardiac
      morphogenesis and electrical conductivity which, when defective, cause the
      tetralogy of Fallot phenotype. Our method implements a whole-phenome approach
      toward disease gene discovery and can be applied to prioritize genes for rare and
      orphan diseases for which the molecular basis is unknown.

PMID- 21737430
TI  - Precise BAC targeting of genetically polymorphic mouse ES cells.
AB  - The use of bacterial artificial chromosomes (BACs) provides a consistent and high
      targeting efficiency of homologous recombination in embryonic stem (ES) cells,
      facilitated by long stretches of sequence homology. Here, we introduce a BAC
      targeting method which employs restriction fragment length polymorphisms (RFLPs)
      in targeted polymorphic C57BL/6/Cast/Ei F1 mouse ES cell lines to identify
      properly targeted ES cell clones. We demonstrate that knockout alleles can be
      generated either by targeting of an RFLP located in the open reading frame
      thereby disrupting the RFLP and ablating gene function, or by introduction of a
      transcription stop cassette that prematurely stops transcription of an RFLP
      located downstream of the stop cassette. With both methods we have generated
      Rnf12 heterozygous knockout ES cells, which were identified by allele specific
      PCR using genomic DNA or cDNA as a template. Our results indicate that this novel
      strategy is efficient and precise, by combining a high targeting efficiency with
      a convenient PCR based readout and reliable detection of correct targeting
      events.

PMID- 21737431
TI  - Classification of pseudo pairs between nucleotide bases and amino acids by
      analysis of nucleotide-protein complexes.
AB  - Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA
      binding and nucleotide binding proteins. In this study, a total of 446 crystal
      structures of nucleotide-protein complexes are analyzed manually and pseudo pairs
      together with single and bifurcated hydrogen bonds observed between bases and
      amino acids are classified and annotated. Only 5 of the 20 usual amino acid
      residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in
      order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The
      peptide backbone can also form pseudo pairs with nucleotide bases and presents a
      strong bias for binding to the adenine base. The Watson-Crick side of the
      nucleotide bases is the major interaction edge participating in such pseudo
      pairs. Pseudo pairs between the Watson-Crick edge of guanine and Asp are
      frequently observed. The Hoogsteen edge of the purine bases is a good
      discriminatory element in recognition of nucleotide bases by protein side chains
      through the pseudo pairing: the Hoogsteen edge of adenine is recognized by
      various amino acids while the Hoogsteen edge of guanine is only recognized by
      Arg. The sugar edge is rarely recognized by either the side-chain or peptide
      backbone of amino acid residues.

PMID- 21737432
TI  - Analysis of nucleic acid chaperoning by the prion protein and its inhibition by
      oligonucleotides.
AB  - Prion diseases are unique neurodegenerative illnesses associated with the
      conversion of the cellular prion protein (PrP(C)) into the aggregated misfolded
      scrapie isoform, named PrP(Sc). Recent studies on the physiological role of
      PrP(C) revealed that this protein has probably multiple functions, notably in
      cell-cell adhesion and signal transduction, and in assisting nucleic acid
      folding. In fact, in vitro findings indicated that the human PrP (huPrP)
      possesses nucleic acid binding and annealing activities, similarly to nucleic
      acid chaperone proteins that play essential roles in cellular DNA and RNA
      metabolism. Here, we show that a peptide, representing the N-terminal domain of
      huPrP, facilitates nucleic acid annealing by two parallel pathways nucleated
      through the stem termini. We also show that PrP of human or ovine origin
      facilitates DNA strand exchange, ribozyme-directed cleavage of an RNA template
      and RNA trans-splicing in a manner similar to the nucleocapsid protein of HIV-1.
      In an attempt to characterize inhibitors of PrP-chaperoning in vitro we
      discovered that the thioaptamer 5'-GACACAAGCCGA-3' was extensively inhibiting the
      PrP chaperoning activities. At the same time a recently characterized methylated
      oligoribonucleotide inhibiting the chaperoning activity of the HIV-1 nucleocapsid
      protein was poorly impairing the PrP chaperoning activities.

PMID- 21737433
TI  - Frontostriatal response to set switching is moderated by reward sensitivity.
AB  - The reinforcement sensitivity theory (RST) relates individual differences in
      reward sensitivity to the activation of the behavioral approach system (BAS).
      Dopamine-related brain structures have been repeatedly associated with reward
      processing, but also with cognitive processes such as task switching. In the
      present study, we examined the association between reward sensitivity and the
      event-related fMRI BOLD response with set switching in 31 males. As expected, the
      right inferior frontal cortex (rIFG) and the striatum (i.e. the left putamen)
      were involved in set-switching activity for the overall sample. Interindividual
      differences in Gray's reward sensitivity were related to stronger activity in the
      rIFG and the ventral striatum. Thus, trait reward sensitivity contributed to the
      modulation of brain responsiveness in set-switching tasks. Having considered
      previous research, we propose that higher BAS activity is associated with a
      stronger reward to process a better implementation of goal-directed tasks and the
      diminished processing of secondary cues.

PMID- 21737434
TI  - Neural systems for social cognition in Klinefelter syndrome (47,XXY): evidence
      from fMRI.
AB  - Klinefelter syndrome (KS) is a chromosomal condition (47, XXY) that may help us
      to unravel gene-brain behavior pathways to psychopathology. The phenotype
      includes social cognitive impairments and increased risk for autism traits. We
      used functional MRI to study neural mechanisms underlying social information
      processing. Eighteen nonclinical controls and thirteen men with XXY were scanned
      during judgments of faces with regard to trustworthiness and age. While judging
      faces as untrustworthy in comparison to trustworthy, men with XXY displayed less
      activation than controls in (i) the amygdala, which plays a key role in screening
      information for socio-emotional significance, (ii) the insula, which plays a role
      in subjective emotional experience, as well as (iii) the fusiform gyrus and (iv)
      the superior temporal sulcus, which are both involved in the perceptual
      processing of faces and which were also less involved during age judgments in men
      with XXY. This is the first study showing that KS can be associated with reduced
      involvement of the neural network subserving social cognition. Studying KS may
      increase our understanding of the genetic and hormonal basis of neural
      dysfunctions contributing to abnormalities in social cognition and behavior,
      which are considered core abnormalities in psychiatric disorders such as autism
      and schizophrenia.

PMID- 21737435
TI  - Empathic neural responses to others' pain depend on monetary reward.
AB  - Human empathy is not merely a resonance with others' physical condition, but is
      modulated by social factors. Using functional magnetic resonance imaging, the
      present study demonstrated an increased brain empathic response to others in pain
      when they received no rather than a large reward, with increments of the ACC,
      aMCC, insula and postcentral gyrus in the pain matrix and temporoparietal
      junction. Thus, pain target's financial situation modulated brain empathic
      responses in the pain matrix based on an understanding of the situation pain
      target faces.

PMID- 21737436
TI  - spacodiR: structuring of phylogenetic diversity in ecological communities.
AB  - MOTIVATION: spacodiR is a cross-platform package, written for the R environment,
      for studying partitioning of diversity among natural communities in space and
      time. Complementing and extending existing software, spacodiR allows for
      hypothesis testing and parameter estimation in studying spatial structuring of
      species-, phylogenetic- and trait diversities. AVAILABILITY: Integrated with
      other software in the R environment and with well documented and demonstrated
      functions, spacodiR is an open-source package and available at http://cran.r
      project.org. CONTACT: jonathan.eastman@gmail.com; ohardy@ulb.ac.be.

PMID- 21737437
TI  - APCluster: an R package for affinity propagation clustering.
AB  - SUMMARY: Affinity propagation (AP) clustering has recently gained increasing
      popularity in bioinformatics. AP clustering has the advantage that it allows for
      determining typical cluster members, the so-called exemplars. We provide an R
      implementation of this promising new clustering technique to account for the
      ubiquity of R in bioinformatics. This article introduces the package and presents
      an application from structural biology. AVAILABILITY: The R package apcluster is
      available via CRAN-The Comprehensive R Archive Network: http://cran.r
      project.org/web/packages/apcluster CONTACT: apcluster@bioinf.jku.at;
      bodenhofer@bioinf.jku.at.

PMID- 21737438
TI  - Simulating systems genetics data with SysGenSIM.
AB  - SUMMARY: SysGenSIM is a software package to simulate Systems Genetics (SG)
      experiments in model organisms, for the purpose of evaluating and comparing
      statistical and computational methods and their implementations for analyses of
      SG data [e.g. methods for expression quantitative trait loci (eQTL) mapping and
      network inference]. SysGenSIM allows the user to select a variety of network
      topologies, genetic and kinetic parameters to simulate SG data ( genotyping, gene
      expression and phenotyping) with large gene networks with thousands of nodes. The
      software is encoded in MATLAB, and a user-friendly graphical user interface is
      provided. AVAILABILITY: The open-source software code and user manual can be
      downloaded at: http://sysgensim.sourceforge.net/ CONTACT: alf@crs4.it.

PMID- 21737439
TI  - The Cardiac Atlas Project--an imaging database for computational modeling and
      statistical atlases of the heart.
AB  - MOTIVATION: Integrative mathematical and statistical models of cardiac anatomy
      and physiology can play a vital role in understanding cardiac disease phenotype
      and planning therapeutic strategies. However, the accuracy and predictive power
      of such models is dependent upon the breadth and depth of noninvasive imaging
      datasets. The Cardiac Atlas Project (CAP) has established a large-scale database
      of cardiac imaging examinations and associated clinical data in order to develop
      a shareable, web-accessible, structural and functional atlas of the normal and
      pathological heart for clinical, research and educational purposes. A goal of CAP
      is to facilitate collaborative statistical analysis of regional heart shape and
      wall motion and characterize cardiac function among and within population groups.
      RESULTS: Three main open-source software components were developed: (i) a
      database with web-interface; (ii) a modeling client for 3D + time visualization
      and parametric description of shape and motion; and (iii) open data formats for
      semantic characterization of models and annotations. The database was implemented
      using a three-tier architecture utilizing MySQL, JBoss and Dcm4chee, in
      compliance with the DICOM standard to provide compatibility with existing
      clinical networks and devices. Parts of Dcm4chee were extended to access image
      specific attributes as search parameters. To date, approximately 3000 de
      identified cardiac imaging examinations are available in the database. All
      software components developed by the CAP are open source and are freely available
      under the Mozilla Public License Version 1.1 (http://www.mozilla.org/MPL/MPL
      1.1.txt). AVAILABILITY: http://www.cardiacatlas.org CONTACT:
      a.young@auckland.ac.nz SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21737440
TI  - International action plan on the radiation protection of patients.
AB  - Realising that the major part of radiation protection efforts had been directed
      for over half a century at radiation protection of workers, and that there are
      major issues in relation to medical exposure, which contributes to over 95 % of
      the dose to the global population from man-made sources, with increasing
      individual patient doses in diagnostic examinations, unnecessary or inappropriate
      examinations and continued accidents in radiotherapy, the International Atomic
      Energy Agency established an International Action Plan (IAP) in 2002 in
      cooperation with international organisations and professional bodies. The
      achievements of the IAP, which include harmonised training material, guidance
      documents, a number of publications, a website on radiation protection of
      patients (http://rpop.iaea.org) and a series of actions in Member States that
      have shown positive impacts on patient protection, are summarised in this paper.

PMID- 21737441
TI  - Medical radiation protection in next decade.
AB  - Interest in medical radiation protection today is the same as what it would have
      been almost a century ago. After many decades of relatively safe application of
      radiation in medicine, the recent spurt in over exposures, over-use of imaging
      and accidental exposures has created the need for stakeholders to join hands and
      contribute towards increasing radiation safety levels. Whether it be the need for
      technological developments to achieve sub-mSv CT scans, tracking of patient
      exposure history, accounting for repeated exposures of the same patient, specific
      consideration of requests for radiological examinations that deliver few mSv of
      dose, or utilization of regulatory approaches, radiological equipment will need
      to alert users whenever the radiation dose to the patient is above a defined
      value. The current decade will focus increasingly on carcinogenic effects in
      patients.

PMID- 21737442
TI  - Skin injuries in interventional procedures.
AB  - Radiation-induced skin injuries to patients in interventional procedures have
      been reported since the early 1990s, but the number reported is far less than
      what might be occurring around the world. There is a gross lack of awareness
      resulting in patients suffering. A case of severe injury observed in multiple
      percutaneous coronary interventions for chronic total occlusion is reported in
      this paper. Further, the paper summarises the existing knowledge on radiation
      dosimetry in interventional procedures, factors involved in skin injury, guidance
      on detection, and avoidance and management of injury when it occurs. Information
      on a recently launched international anonymous reporting system of the
      International Atomic Energy Agency is also included.

PMID- 21737443
TI  - Effective dose for scoliosis patients undergoing full spine radiography.
AB  - Scoliotic patients underwent many radiological examinations during their control
      and treatment periods. Nowadays, few studies have calculated effective dose which
      is the primary indicator of radiation risk. In this study, the PCXMC program is
      used to calculate the effective doses associated with scoliosis radiography. Five
      age groups of patients, proposed by the National Radiological Protection Board,
      have been chosen: <1, 1-4, 5-9, 10-15 and >=16 y (adult patients). Patient and
      radiographic data were collected from 99 patient examinations for both
      anteroposterior and lateral full spine X-ray projections. Results showed the
      effective dose ranged from 118 to 1596 MUSv for the frontal projection and from
      97 to 1370 MUSv for the lateral projection, with patient age varying from 3
      months to 22 y. This study presents the effective dose against patient age and
      demonstrates the necessity to optimise patient protection for this type of
      examination.

PMID- 21737444
TI  - Involvement of insulin-like growth factor-binding protein-3 in the effects of
      histone deacetylase inhibitor MS-275 in hepatoma cells.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) expression is frequently
      suppressed in liver cancers and can be reactivated by histone deacetylase (HDAC)
      inhibition. This study examined the role of IGFBP-3 in mediating the effects of
      the HDAC inhibitor MS-275 in liver cancer cells and identified IGFBP-3-dependent
      proteins that regulate proliferation and migration. In HepG2 cells, MS-275
      inhibited DNA synthesis, cell cycle activity, and cell viability concomitantly
      with increased binding of acetylated histone H3 to IGFBP-3 promoter sequences and
      induction of IGFBP-3 expression. IGFBP-3 down-regulation by siRNA significantly
      reversed the inhibition of cell viability and DNA synthesis by MS-275, indicating
      an intermediary role for IGFBP-3. Induction of the cyclin-dependent kinase
      inhibitor p21 by MS-275 was attenuated by IGFBP-3 down-regulation, providing an
      explanation for IGFBP-3-dependent effects of MS-275 on cell cycle activity. In
      contrast, MS-275 stimulated HepG2 cell migration, an effect also inhibited by
      IGFBP-3 down-regulation. Among genes whose induction by MS-275 was attenuated by
      IGFBP-3 down-regulation, LYVE1 and THBS2 (thrombospondin-2) were identified as
      mediators of IGFBP-3-dependent effects of MS-275. Silencing of either protein had
      no effect on the inhibition of HepG2 viability by MS-275 but reversed its
      stimulatory effect on cell migration. We conclude that among genes up-regulated
      by MS-275, IGFBP-3 is a key mediator of effects on hepatoma cell growth and
      migration, involving IGFBP-3-dependent proteins p21 (proliferation) and LYVE1 and
      THBS2 (migration). The enhanced cell motility that accompanies reactivation of
      IGFBP-3 expression in liver cancer by HDAC inhibition suggests the possibility of
      increased metastatic spread despite inhibited cell proliferation.

PMID- 21737445
TI  - Phosphatidic acid activates mammalian target of rapamycin complex 1 (mTORC1)
      kinase by displacing FK506 binding protein 38 (FKBP38) and exerting an allosteric
      effect.
AB  - Phosphatidic acid (PA) is a critical mediator of mitogenic activation of
      mammalian target of rapamycin complex 1 (mTORC1) signaling, a master regulator of
      mammalian cell growth and proliferation. The mechanism by which PA activates
      mTORC1 signaling has remained unknown. Here, we report that PA selectively
      stimulates mTORC1 but not mTORC2 kinase activity in cells and in vitro.
      Furthermore, we show that PA competes with the mTORC1 inhibitor, FK506 binding
      protein 38 (FKBP38), for mTOR binding at a site encompassing the rapamycin-FKBP12
      binding domain. This leads to PA antagonizing FKBP38 inhibition of mTORC1 kinase
      activity in vitro and rescuing mTORC1 signaling from FKBP38 in cells.
      Phospholipase D 1, a PA-generating enzyme that is an established upstream
      regulator of mTORC1, is found to negatively affect mTOR-FKBP38 interaction,
      confirming the role of endogenous PA in this regulation. Interestingly, removal
      of FKBP38 alone is insufficient to activate mTORC1 kinase and signaling, which
      require PA even when the FKBP38 level is drastically reduced by RNAi. In
      conclusion, we propose a dual mechanism for PA activation of mTORC1: PA displaces
      FKBP38 from mTOR and allosterically stimulates the catalytic activity of mTORC1.

PMID- 21737446
TI  - Impact of primer-induced conformational dynamics of HIV-1 reverse transcriptase
      on polymerase translocation and inhibition.
AB  - The rapid emergence and the prevalence of resistance mutations in HIV-1 reverse
      transcriptase (RT) underscore the need to identify RT inhibitors with novel
      binding modes and mechanisms of inhibition. Recently, two structurally distinct
      inhibitors, phosphonoformic acid (foscarnet) and INDOPY-1 were shown to disrupt
      the translocational equilibrium of RT during polymerization through trapping of
      the enzyme in the pre- and the post-translocation states, respectively. Here, we
      show that foscarnet and INDOPY-1 additionally display a shared novel inhibitory
      preference with respect to substrate primer identity. In RT-catalyzed reactions
      using RNA-primed substrates, translocation inhibitors were markedly less potent
      at blocking DNA polymerization than in equivalent DNA-primed assays; i.e. the
      inverse pattern observed with marketed non-nucleoside inhibitors that bind the
      allosteric pocket of RT. This potency profile was shown to correspond with
      reduced binding on RNA.DNA primer/template substrates versus DNA.DNA substrates.
      Furthermore, using site-specific footprinting with chimeric RNA.DNA primers, we
      demonstrate that the negative impact of the RNA primer on translocation inhibitor
      potency is overcome after 18 deoxyribonucleotide incorporations, where RT
      transitions primarily into polymerization-competent binding mode. In addition to
      providing a simple means to identify similarly acting translocation inhibitors,
      these findings suggest a broader role for the primer-influenced binding mode on
      RT translocation equilibrium and inhibitor sensitivity.

PMID- 21737447
TI  - Role of novel dimeric Photosystem II (PSII)-Psb27 protein complex in PSII repair.
AB  - The multisubunit membrane protein complex Photosystem II (PSII) catalyzes one of
      the key reactions in photosynthesis: the light-driven oxidation of water. Here,
      we focus on the role of the Psb27 assembly factor, which is involved in
      biogenesis and repair after light-induced damage of the complex. We show that
      Psb27 is essential for the survival of cyanobacterial cells grown under stress
      conditions. The combination of cold stress (30  degrees C) and high light stress
      (1000 MUmol of photons * m(-2) * s(-1)) led to complete inhibition of growth in a
      Deltapsb27 mutant strain of the thermophilic cyanobacterium Thermosynechococcus
      elongatus, whereas wild-type cells continued to grow. Moreover, Psb27-containing
      PSII complexes became the predominant PSII species in preparations from wild-type
      cells grown under cold stress. Two different PSII-Psb27 complexes were isolated
      and characterized in this study. The first complex represents the known monomeric
      PSII-Psb27 species, which is involved in the assembly of PSII. Additionally, a
      novel dimeric PSII-Psb27 complex could be allocated in the repair cycle, i.e. in
      processes after inactivation of PSII, by (15)N pulse-label experiments followed
      by mass spectrometry analysis. Comparison with the corresponding PSII species
      from Deltapsb27 mutant cells showed that Psb27 prevented the release of manganese
      from the previously inactivated complex. These results indicate a more complex
      role of the Psb27 protein within the life cycle of PSII, especially under stress
      conditions.

PMID- 21737448
TI  - CaV1.3 channels and intracellular calcium mediate osmotic stress-induced N
      terminal c-Jun kinase activation and disruption of tight junctions in Caco-2 CELL
      MONOLAYERS.
AB  - We investigated the role of a Ca(2+) channel and intracellular calcium
      concentration ([Ca(2+)](i)) in osmotic stress-induced JNK activation and tight
      junction disruption in Caco-2 cell monolayers. Osmotic stress-induced tight
      junction disruption was attenuated by 1,2-bis(2-aminophenoxyl)ethane-N,N,N',N'
      tetraacetic acid (BAPTA)-mediated intracellular Ca(2+) depletion. Depletion of
      extracellular Ca(2+) at the apical surface, but not basolateral surface, also
      prevented tight junction disruption. Similarly, thapsigargin-mediated endoplasmic
      reticulum (ER) Ca(2+) depletion attenuated tight junction disruption.
      Thapsigargin or extracellular Ca(2+) depletion partially reduced osmotic stress
      induced rise in [Ca(2+)](i), whereas thapsigargin and extracellular Ca(2+)
      depletion together resulted in almost complete loss of rise in [Ca(2+)](i). L
      type Ca(2+) channel blockers (isradipine and diltiazem) or knockdown of the
      Ca(V)1.3 channel abrogated [Ca(2+)](i) rise and disruption of tight junction.
      Osmotic stress-induced JNK2 activation was abolished by BAPTA and isradipine, and
      partially reduced by extracellular Ca(2+) depletion, thapsigargin, or Ca(V)1.3
      knockdown. Osmotic stress rapidly induced c-Src activation, which was
      significantly attenuated by BAPTA, isradipine, or extracellular Ca(2+) depletion.
      Tight junction disruption by osmotic stress was blocked by tyrosine kinase
      inhibitors (genistein and PP2) or siRNA-mediated knockdown of c-Src. Osmotic
      stress induced a robust increase in tyrosine phosphorylation of occludin, which
      was attenuated by BAPTA, SP600125 (JNK inhibitor), or PP2. These results
      demonstrate that Ca(V)1.3 and rise in [Ca(2+)](i) play a role in the mechanism of
      osmotic stress-induced tight junction disruption in an intestinal epithelial
      monolayer. [Ca(2+)](i) mediate osmotic stress-induced JNK activation and
      subsequent c-Src activation and tyrosine phosphorylation of tight junction
      proteins. Additionally, inositol 1,4,5-trisphosphate receptor-mediated release of
      ER Ca(2+) also contributes to osmotic stress-induced tight junction disruption.

PMID- 21737449
TI  - The nucleophosmin-anaplastic lymphoma kinase oncogene interacts, activates, and
      uses the kinase PIKfyve to increase invasiveness.
AB  - NPM-ALK is a chimeric tyrosine kinase detected in most anaplastic large cell
      lymphomas that results from the reciprocal translocation t(2,5)(p23;q35) that
      fuses the N-terminal domain of nucleophosmin (NPM) to the catalytic domain of the
      anaplastic lymphoma kinase (ALK) receptor. The constitutive activity of the
      kinase is responsible for its oncogenicity through the stimulation of several
      downstream signaling pathways, leading to cell proliferation, migration, and
      survival. We demonstrated previously that the high level of phosphatidylinositol
      5-phosphate measured in NPM-ALK-expressing cells is controlled by the
      phosphoinositide kinase PIKfyve, a lipid kinase known for its role in vesicular
      trafficking. Here, we show that PIKfyve associates with NPM-ALK and that the
      interaction involves the 181-300 region of the oncogene. Moreover, we demonstrate
      that the tyrosine kinase activity of the oncogene controls PIKfyve lipid kinase
      activity but is dispensable for the formation of the complex. Silencing or
      inhibition of PIKfyve using siRNA or the PIKfyve inhibitor YM201636 have no
      effect on NPM-ALK-mediated proliferation and migration but strongly reduce
      invasive capacities of NPM-ALK-expressing cells and their capacity to degrade the
      extracellular matrix. Accordingly, immunofluorescence studies confirm a
      perturbation of matrix metalloproteinase 9 localization at the cell surface and
      defect in maturation. Altogether, these results suggest a role for PIKfyve in NPM
      ALK-mediated invasion.

PMID- 21737450
TI  - Functional and structural insights into ASB2alpha, a novel regulator of integrin
      dependent adhesion of hematopoietic cells.
AB  - By providing contacts between hematopoietic cells and the bone marrow
      microenvironment, integrins are implicated in cell adhesion and thereby in
      control of cell fate of normal and leukemia cells. The ASB2 gene, initially
      identified as a retinoic acid responsive gene and a target of the promyelocytic
      leukemia retinoic acid receptor alpha oncoprotein in acute promyelocytic leukemia
      cells, encodes two isoforms, a hematopoietic-type (ASB2alpha) and a muscle-type
      (ASB2beta) that are involved in hematopoietic and myogenic differentiation,
      respectively. ASB2alpha is the specificity subunit of an E3 ubiquitin ligase
      complex that targets filamins to proteasomal degradation. To examine the
      relationship of the ASB2alpha structure to E3 ubiquitin ligase function,
      functional assays and molecular modeling were performed. We show that ASB2alpha,
      through filamin A degradation, enhances adhesion of hematopoietic cells to
      fibronectin, the main ligand of beta1 integrins. Furthermore, we demonstrate that
      a short N-terminal region specific to ASB2alpha, together with ankyrin repeats 1
      to 10, is necessary for association of ASB2alpha with filamin A. Importantly, the
      ASB2alpha N-terminal region comprises a 9-residue segment with predicted
      structural homology to the filamin-binding motifs of migfilin and beta integrins.
      Together, these data provide new insights into the molecular mechanisms of
      ASB2alpha binding to filamin.

PMID- 21737451
TI  - Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is
      facilitated by Tamm-Horsfall protein in a chloride-sensitive manner.
AB  - Active transport of NaCl across thick ascending limb (TAL) epithelium is
      accomplished by Na(+),K(+),2Cl(-) cotransporter (NKCC2). The activity of NKCC2 is
      determined by vasopressin (AVP) or intracellular chloride concentration and
      includes its amino-terminal phosphorylation. Co-expressed Tamm-Horsfall protein
      (THP) has been proposed to interact with NKCC2. We hypothesized that THP
      modulates NKCC2 activity in TAL. THP-deficient mice (THP(-/-)) showed an
      increased abundance of intracellular NKCC2 located in subapical vesicles (+47%
      compared with wild type (WT) mice), whereas base-line phosphorylation of NKCC2
      was significantly decreased (-49% compared with WT mice), suggesting reduced
      activity of the transporter in the absence of THP. Cultured TAL cells with low
      endogenous THP levels and low base-line phosphorylation of NKCC2 displayed sharp
      increases in NKCC2 phosphorylation (+38%) along with a significant change of
      intracellular chloride concentration upon transfection with THP. In NKCC2
      expressing frog oocytes, co-injection with THP cRNA significantly enhanced the
      activation of NKCC2 under low chloride hypotonic stress (+112% versus +235%).
      Short term (30 min) stimulation of the vasopressin V2 receptor pathway by V2
      receptor agonist (deamino-cis-D-Arg vasopressin) resulted in enhanced NKCC2
      phosphorylation in WT mice and cultured TAL cells transfected with THP, whereas
      in the absence of THP, NKCC2 phosphorylation upon deamino-cis-D-Arg vasopressin
      was blunted in both systems. Attenuated effects of furosemide along with
      functional and structural adaptation of the distal convoluted tubule in THP(-/-)
      mice supported the notion that NaCl reabsorption was impaired in TAL lacking THP.
      In summary, these results are compatible with a permissive role for THP in the
      modulation of NKCC2-dependent TAL salt reabsorptive function.

PMID- 21737452
TI  - DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike
      subtype of hepatocellular carcinoma associated with poor survival.
AB  - Hepatocellular carcinoma (HCC) is a heterogeneous and highly aggressive
      malignancy, for which there are no effective cures. Identification of a malignant
      stemlike subtype of HCC may offer patients with a dismal prognosis a potential
      targeted therapy using c-MET and Wnt pathway inhibitors. MicroRNAs (miRNAs) show
      promise as diagnostic and prognostic tools for cancer detection and
      stratification. Using a TRE-c-Met-driven transgenic HCC mouse model, we
      identified a cluster of 23 miRNAs that is encoded within the Dlk1-Gtl2 imprinted
      region on chromosome 12qF1 overexpressed in all of the isolated liver tumors.
      Interestingly, this region is conserved among mammalian species and maps to the
      human DLK1-DIO3 region on chromosome 14q32.2. We thus examined the expression of
      the DLK1-DIO3 miRNA cluster in a cohort of 97 hepatitis B virus-associated HCC
      patients and identified a subgroup (n = 18) of patients showing strong coordinate
      overexpression of miRNAs in this cluster but not in other cancer types (breast,
      lung, kidney, stomach, and colon) that were tested. Expression levels of
      imprinted gene transcripts from neighboring loci in this 14q32.2 region and from
      a subset of other imprinted sites were concomitantly elevated in human HCC.
      Interestingly, overexpression of the DLK1-DIO3 miRNA cluster was positively
      correlated with HCC stem cell markers (CD133, CD90, EpCAM, Nestin) and associated
      with a high level of serum alpha-fetoprotein, a conventional biomarker for liver
      cancer, and poor survival rate in HCC patients. In conclusion, our findings
      suggest that coordinate up-regulation of the DLK1-DIO3 miRNA cluster at 14q32.2
      may define a novel molecular (stem cell-like) subtype of HCC associated with poor
      prognosis.

PMID- 21737453
TI  - Expression of truncated eukaryotic initiation factor 3e (eIF3e) resulting from
      integration of mouse mammary tumor virus (MMTV) causes a shift from cap-dependent
      to cap-independent translation.
AB  - Integration of mouse mammary tumor virus (MMTV) at the common integration site
      Int6 occurs in the gene encoding eIF3e, the p48 subunit of translation initiation
      factor eIF3. Integration is at any of several introns of the Eif3e gene and
      causes the expression of truncated Eif3e mRNAs. Ectopic expression of the
      truncated eIF3e protein resulting from integration at intron 5 (3e5) induces
      malignant transformation, but by an unknown mechanism. Because eIF3e makes up at
      least part of the binding site for eIF4G, we examined the effects of 3e5
      expression on protein synthesis. We developed an NIH3T3 cell line that contains a
      single copy of the 3e5 sequence at a predetermined genomic site. Co
      immunoprecipitation indicated diminished binding of eIF3 to eIF4G, signifying a
      reduction in recruitment of the mRNA-unwinding machinery to the 43 S
      preinitiation complex. Cell growth and overall protein synthesis were decreased.
      Translation driven by the eIF4G-independent hepatitis C virus internal ribosome
      entry sequence (HCV IRES) in a bicistronic mRNA was increased relative to cap
      dependent translation. Endogenous mRNAs encoding XIAP, c-Myc, CYR61, and Pim-1,
      which are translated in a cap-independent manner, were shifted to heavier
      polysomes whereas mRNAs encoding GAPDH, actin, L32, and L34, which are translated
      in a cap-dependent manner, were shifted to lighter polysomes. We propose that
      expression of 3e5 diminishes eIF4G interaction with eIF3 and causes abnormal gene
      expression at the translational level. The correlation between up-regulation of
      cap-independent translation and MMTV-induced tumorigenesis contrasts with the
      well established model for malignant transformation involving up-regulation of
      highly cap-dependent translation.

PMID- 21737454
TI  - Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its
      orphan domain, inhibits blood vessel formation, and suppresses tumor growth.
AB  - Endoglin (CD105), a transmembrane protein of the transforming growth factor beta
      superfamily, plays a crucial role in angiogenesis. Mutations in endoglin result
      in the vascular defect known as hereditary hemorrhagic telangiectasia (HHT1). The
      soluble form of endoglin was suggested to contribute to the pathogenesis of
      preeclampsia. To obtain further insight into its function, we cloned, expressed,
      purified, and characterized the extracellular domain (ECD) of mouse and human
      endoglin fused to an immunoglobulin Fc domain. We found that mouse and human
      endoglin ECD-Fc bound directly, specifically, and with high affinity to bone
      morphogenetic proteins 9 and 10 (BMP9 and BMP10) in surface plasmon resonance
      (Biacore) and cell-based assays. We performed a function mapping analysis of the
      different domains of endoglin by examining their contributions to the selectivity
      and biological activity of the protein. The BMP9/BMP10 binding site was localized
      to the orphan domain of human endoglin composed of the amino acid sequence 26
      359. We established that endoglin and type II receptors bind to overlapping sites
      on BMP9. In the in vivo chick chorioallantoic membrane assay, the mouse and the
      truncated human endoglin ECD-Fc both significantly reduced VEGF-induced vessel
      formation. Finally, murine endoglin ECD-Fc acted as an anti-angiogenic factor
      that decreased blood vessel sprouting in VEGF/FGF-induced angiogenesis in in vivo
      angioreactors and reduced the tumor burden in the colon-26 mouse tumor model.
      Together our findings indicate an important role of soluble endoglin ECD in the
      regulation of angiogenesis and highlight efficacy of endoglin-Fc as a potential
      anti-angiogenesis therapeutic agent.

PMID- 21737455
TI  - Hepatitis C virus is primed by CD81 protein for low pH-dependent fusion.
AB  - Hepatitis C virus (HCV) entry into permissive cells is a complex process that
      involves interactions with at least four co-factors followed by endocytosis and
      low pH-dependent fusion with endosomes. The precise sequence of receptor
      engagement and their roles in promoting HCV E1E2 glycoprotein-mediated fusion are
      poorly characterized. Because cell-free HCV tolerates an acidic environment, we
      hypothesized that binding to one or more receptors on the cell surface renders
      E1E2 competent to undergo low pH-induced conformational changes and promote
      fusion with endosomes. To test this hypothesis, we examined the effects of low pH
      and of the second extracellular loop (ECL2) of CD81, one of the four entry
      factors, on HCV infectivity. Pretreatment with an acidic buffer or with ECL2
      enhanced infection through changing the E1E2 conformation, as evidenced by the
      altered reactivity of these proteins with conformation-specific antibodies and
      stable association with liposomes. However, neither of the two treatments alone
      permitted direct fusion with the cell plasma membrane. Sequential HCV
      preincubation with ECL2 and acidic buffer in the absence of target cells resulted
      in a marked loss of infectivity, implying that the receptor-bound HCV is primed
      for low pH-dependent conformational changes. Indeed, soluble receptor-pretreated
      HCV fused with the cell plasma membrane at low pH under conditions blocking an
      endocytic entry pathway. These findings suggest that CD81 primes HCV for low pH
      dependent fusion early in the entry process. The simple triggering paradigm and
      intermediate conformations of E1E2 identified in this study could help guide
      future vaccine and therapeutic efforts to block HCV infection.

PMID- 21737456
TI  - Insights into the Clp/HSP100 chaperone system from chloroplasts of Arabidopsis
      thaliana.
AB  - HSP100 proteins are molecular chaperones involved in protein quality control.
      They assist in protein (un)folding, prevent aggregation, and are thought to
      participate in precursor translocation across membranes. Caseinolytic proteins
      ClpC and ClpD from plant chloroplasts belong to the HSP100 family. Their role has
      hitherto been investigated by means of physiological studies and reverse
      genetics. In the present work, we employed an in vitro approach to delve into the
      structural and functional characteristics of ClpC2 and ClpD from Arabidopsis
      thaliana (AtClpC2 and AtClpD). They were expressed in Escherichia coli and
      purified to near-homogeneity. The proteins were detected mainly as dimers in
      solution, and, upon addition of ATP, the formation of hexamers was observed. Both
      proteins exhibited basal ATPase activity (K(m), 1.42 mm, V(max), 0.62 nmol/(min *
      MUg) for AtClpC2 and K(m) ~19.80 mm, V(max) ~0.19 nmol/(min * MUg) for AtClpD).
      They were able to reactivate the activity of heat-denatured luciferase (~40% for
      AtClpC2 and ~20% for AtClpD). The Clp proteins tightly bound a fusion protein
      containing a model transit peptide. This interaction was detected by binding
      assays, where the chaperones were selectively trapped by the transit peptide
      containing fusion, immobilized on glutathione-agarose beads. Association of
      HSP100 proteins to import complexes with a bound transit peptide-containing
      fusion was also observed in intact chloroplasts. The presented data are useful to
      understand protein quality control and protein import into chloroplasts in
      plants.

PMID- 21737457
TI  - Deaminase activity on single-stranded DNA (ssDNA) occurs in vitro when APOBEC3G
      cytidine deaminase forms homotetramers and higher-order complexes.
AB  - APOBEC3G (A3G) is a cytidine deaminase that catalyzes deamination of
      deoxycytidine (dC) on single-stranded DNA (ssDNA). The oligomeric state of A3G
      required to support deaminase activity remains unknown. We show under defined in
      vitro conditions that full-length and native A3G formed complexes with ssDNA in
      an A3G concentration-dependent but temperature-independent manner. Complexes
      assembled and maintained at 4  degrees C did not have significant deaminase
      activity, but their enzymatic function could be restored by subsequent incubation
      at 37  degrees C. This approach enabled complexes of a defined size range to be
      isolated and subsequently evaluated for their contribution to enzymatic activity.
      The composition of A3G bound to ssDNA was determined by protein-protein chemical
      cross-linking. A3G-ssDNA complexes of 16 S were necessary for deaminase activity
      and consisted of cross-linked A3G homotetramers and homodimers. At lower
      concentrations, A3G only formed 5.8 S homodimers on ssDNA with low deaminase
      activity. Monomeric A3G was not identified in 5.8 S or 16 S complexes. We propose
      that deaminase-dependent antiviral activity of A3G in vivo may require a critical
      concentration of A3G in viral particles that will promote oligomerization on
      ssDNA during reverse transcription.

PMID- 21737458
TI  - Reaction of vascular adhesion protein-1 (VAP-1) with primary amines: mechanistic
      insights from isotope effects and quantitative structure-activity relationships.
AB  - Human vascular adhesion protein-1 (VAP-1) is an endothelial copper-dependent
      amine oxidase involved in the recruitment and extravasation of leukocytes at
      sites of inflammation. VAP-1 is an important therapeutic target for several
      pathological conditions. We expressed soluble VAP-1 in HEK293 EBNA1 cells at
      levels suitable for detailed mechanistic studies with model substrates. Using the
      model substrate benzylamine, we analyzed the steady-state kinetic parameters of
      VAP-1 as a function of solution pH. We found two macroscopic pK(a) values that
      defined a bell-shaped plot of turnover number k(cat,app) as a function of pH,
      representing ionizable groups in the enzyme-substrate complex. The dependence of
      (k(cat)/K(m))(app) on pH revealed a single pK(a) value (~9) that we assigned to
      ionization of the amine group in free benzylamine substrate. A kinetic isotope
      effect (KIE) of 6 to 7.6 on (k(cat)/K(m))(app) over the pH range of 6 to 10 was
      observed with d(2)-benzylamine. Over the same pH range, the KIE on k(cat) was
      found to be close to unity. The unusual KIE values on (k(cat)/K(m))(app) were
      rationalized using a mechanistic scheme that includes the possibility of multiple
      isotopically sensitive steps. We also report the analysis of quantitative
      structure-activity relationships (QSAR) using para-substituted protiated and
      deuterated phenylethylamines. With phenylethylamines we observed a large KIE on
      k(cat,app) (8.01 +/- 0.28 with phenylethylamine), indicating that C-H bond
      breakage is limiting for 2,4,5-trihydroxyphenylalanine quinone reduction. Poor
      correlations were observed between steady-state rate constants and QSAR
      parameters. We show the importance of combining KIE, QSAR, and structural studies
      to gain insight into the complexity of the VAP-1 steady-state mechanism.

PMID- 21737459
TI  - Is methicillin-resistant Staphylococcus aureus replacing methicillin-susceptible
      S. aureus?
AB  - Despite extensive research on the emergence of and treatments for methicillin
      resistant Staphylococcus aureus (MRSA), prior studies have not rigorously
      evaluated the impact of methicillin resistance on the overall incidence of S.
      aureus infections. Yet, there are direct clinical and research implications of
      determining whether methicillin-susceptible S. aureus (MSSA) infection rates
      remain stable in the face of increasing MRSA prevalence or whether MSSA will be
      replaced over time. A synthesis of prior studies indicates that the emergence of
      healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) has
      led to an increase in the overall incidence of S. aureus infections, with MRSA
      principally adding to, rather than replacing, MSSA. However, colonization with CA
      MRSA may at least partially replace colonization with MSSA. So far, evidence
      indicates that MSSA still accounts for many infections. Therefore, eradication of
      MRSA alone is not sufficient to address the public health burden of S. aureus.

PMID- 21737460
TI  - Socioeconomic status and the trajectory of self-rated health.
AB  - BACKGROUND: self-rated health (SRH) likely reflects both mental and physical
      health domains, and is assessed by asking individuals to describe their health
      status. Poor SRH is associated with disease incidence and subsequent mortality.
      Changes in SRH across time in persons with different incident diseases are
      uncharacterised. METHODS: SRH was assessed in the Atherosclerosis Risk in
      Communities study via annual telephone interviews over a median of 17.6 years.
      Individual quadratic growth models were used for repeated measures of SRH in
      persons who remained disease-free during follow-up (n = 11,188), as well as among
      those who were diagnosed with myocardial infarction (MI; n = 1,071), stroke (n =
      809), heart failure (HF; n = 1,592) or lung cancer (n = 433) and those who
      underwent a cardiac revascularisation procedure (n = 1,340) during follow-up.
      RESULTS: among disease-free participants and across time, there was a trend for
      lowest mean SRH among persons living in low socioeconomic areas and highest mean
      SRH among persons living in high socioeconomic areas. Factors contributing to the
      decline in SRH over time included advanced age, lower educational attainment,
      smoking and obesity. CONCLUSION: addressing factors related to poor SRH
      trajectories among patients pre- and post-incident disease may favourably affect
      health outcomes among patients regardless of type of disease.

PMID- 21737461
TI  - Onset of mobility limitations in old age: the combined effect of socioeconomic
      position and social relations.
AB  - PURPOSE: to examine the combined effect of cohabitation status and social
      participation, respectively, and socioeconomic position on onset of mobility
      limitations in a prospective study among older Danes. DESIGN AND METHODS:
      logistic regression analyses with combined exposure variables were performed in a
      study population of 2,839 older men and women from the Danish Intervention Study
      on Preventive Home Visits. RESULTS: among men low financial assets, living alone
      or having low social participation significantly increased the odds ratios (OR)
      for onset of mobility limitations. Among women only low financial assets and low
      social participation significantly increased the ORs for onset of mobility
      limitations. Analyses with combined exposure variables showed that simultaneous
      exposure to low financial assets and poor social relations significantly
      increased the ORs for onset of mobility limitations among both genders, yet the
      tendencies appeared stronger for males. In particular, men with simultaneous
      exposure to low financial assets and low social participation had increased odds
      ratios for onset of mobility limitations, OR = 5.36 (2.51-11.47), compared with
      the non-exposed. CONCLUSION: the study suggests that future interventions to
      increase social participation might alleviate the negative effects on mobility
      experienced by older people in low socioeconomic position, perhaps especially
      among older males.

PMID- 21737462
TI  - Effects of different antimicrobial treatments on serum acute phase responses and
      leucocyte counts in pigs after a primary and a secondary challenge infection with
      Actinobacillus pleuropneumoniae.
AB  - The susceptibility to an initial challenge and a re-challenge inoculation with
      Actinobacillus pleuropneumoniae was analysed in pigs that were treated with
      antimicrobials of different efficacies following the first exposure to A
      pleuropneumoniae. In brief, 30 nine-week-old specific pathogen-free pigs were
      allocated to five groups of six. After acclimatisation, four groups were
      inoculated with A pleuropneumoniae serotype 2. At the onset of clinical signs,
      three of the groups of pigs were treated with enrofloxacin, tetracycline or
      penicillin. A fourth group served as the inoculated control and the fifth group
      as a control group that had not been inoculated. On day 28, all five groups were
      re-challenged with the same strain of A pleuropneumoniae serotype 2 as had been
      used in the first inoculation. No treatments were carried out at this time. The
      acute phase responses and differential leucocyte counts were monitored in detail
      after both inoculations. Leucocytosis and acute phase responses in the forms of
      serum amyloid A, pig-major acute phase protein and haptoglobin were recorded in
      all of the inoculated groups after the onset of clinical signs following the
      first inoculation. A porcine mannan-binding lectin-A response was less evident in
      the pigs. Acute phase responses resembling those of the first inoculation were
      observed in the pigs that had not previously been inoculated and in the pigs
      treated with enrofloxacin. Acute phase responses were not recorded in the other
      three groups, where the pigs had seroconverted to A pleuropneumoniae serotype 2
      following the first inoculation.

PMID- 21737463
TI  - Systematic reviews and meta-analyses of preclinical studies: publication bias in
      laboratory animal experiments.
AB  - In 2006, Peters et al. identified 86 systematic reviews (SRs) of laboratory
      animal experiments (LAEs). They found 46 LAE meta-analyses (MAs), often of poor
      quality. Six of these 46 MAs tried to assess publication bias. Publication bias
      is the phenomenon of an experiment's results determining its likelihood of
      publication, often over-representing positive findings. As such, publication bias
      is the Achilles heel of any SR. Since researchers increasingly become aware of
      the fact that SRs directly support the 'three Rs', we expect the number of SRs of
      LAEs will sharply increase. Therefore, it is useful to see how publication bias
      is dealt with. Our objective was to identify all SRs and MAs of LAEs where the
      purpose was to inform human health published between July 2005 and 2010 with
      special attention to MAs' quality features and publication bias. We
      systematically searched Medline, Embase, Toxline and ScienceDirect from July 2005
      to 2010, updating Peters' review. LAEs not directly informing human health or
      concerning fundamental biology were excluded. We found 2780 references of which
      163 met the inclusion criteria: 158 SRs, of which 30 performed an MA, and five
      MAs without an SR. The number of SRs roughly doubled every three years since
      1997. The number of MAs roughly doubled every five years since 1999. Compared
      with before July 2005, more MAs were preceded by SR and reported on (quality)
      features of included studies and heterogeneity. A statistically significant
      proportion of MAs considered publication bias (26/35) and tried to formally
      assess it (21/35).

PMID- 21737464
TI  - Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in
      acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.
AB  - BACKGROUND: TNK-S2B, an innovative, randomized, seamless phase II/III trial of
      tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow
      enrollment before regulatory approval of use of phase II patients in phase III.
      PURPOSE: (1) To review the trial design and comprehensive type I error rate
      simulations and (2) to discuss issues raised during regulatory review, to
      facilitate future approval of similar designs. METHODS: In phase II, an early (24
      h) outcome and adaptive sequential procedure selected one of three tenecteplase
      doses for phase III comparison with rt-PA. Decision rules comparing this dose to
      rt-PA would cause stopping for futility at phase II end, or continuation to phase
      III. Phase III incorporated two co-primary hypotheses, allowing for a treatment
      effect at either end of the trichotomized Rankin scale. Assuming no early
      termination, four interim analyses and one final analysis of 1908 patients
      provided an experiment-wise type I error rate of <0.05. RESULTS: Over 1,000
      distribution scenarios, each involving 40,000 replications, the maximum type I
      error in phase III was 0.038. Inflation from the dose selection was more than
      offset by the one-half continuity correction in the test statistics. Inflation
      from repeated interim analyses was more than offset by the reduction from the
      clinical stopping rules for futility at the first interim analysis. LIMITATIONS:
      Design complexity and evolving regulatory requirements lengthened the review
      process. CONCLUSIONS: (1) The design was innovative and efficient. Per protocol,
      type I error was well controlled for the co-primary phase III hypothesis tests,
      and experiment-wise. (2a) Time must be allowed for communications with regulatory
      reviewers from first design stages. (2b) Adequate type I error control must be
      demonstrated. (2c) Greater clarity is needed on (i) whether this includes
      demonstration of type I error control if the protocol is violated and (ii)
      whether simulations of type I error control are acceptable. (2d) Regulatory
      agency concerns that protocols for futility stopping may not be followed may be
      allayed by submitting interim analysis results to them as these analyses occur.

PMID- 21737465
TI  - Steroid hormone modulation of RET through two estrogen responsive enhancers in
      breast cancer.
AB  - RET, a gene causatively mutated in Hirschsprung disease and cancer, has recently
      been implicated in breast cancer estrogen (E2) independence and tamoxifen
      resistance. RET displays both E2 and retinoic acid (RA)-dependent transcriptional
      modulation in E2-responsive breast cancers. However, the regulatory elements
      through which the steroid hormone transcriptional regulation of RET is mediated
      are poorly defined. Recent genome-wide chromatin immunoprecipitation-based
      studies have identified 10 putative E2 receptor-alpha (ESR1) and RA receptor
      alpha-binding sites at the RET locus, of which we demonstrate only two (RET -49.8
      and RET +32.8) display significant E2 regulatory response when assayed
      independently in MCF-7 breast cancer cells. We demonstrate that endogenous RET
      expression and RET -49.8 regulatory activity are cooperatively regulated by E2
      and RA in breast cancer cells. We identify key sequences that are required for
      RET -49.8 and RET +32.8 E2 responsiveness, including motifs known to be bound by
      ESR1, FOXA1 and TFAP2C. We also report that both RET -49.8 regulatory activity
      and endogenous RET expression are completely dependent on ESR1 for their (E2)
      induction and that ESR1 is sufficient to mediate the E2-induced enhancer activity
      of RET -49.8 and RET +32.8. Finally, using zebrafish transgenesis, we also
      demonstrate that RET -49.8 directs reporter expression in the central nervous
      system and peripheral nervous system consistent with the endogenous ret
      expression. Taken collectively, these data suggest that RET transcription in
      breast cancer cells is modulated by E2 via ESR1 acting on multiple elements
      collectively.

PMID- 21737466
TI  - Transoral robotic surgery for the treatment of head and neck cancer of various
      localizations.
AB  - BACKGROUND: Transoral robotic surgery (TORS) is a recent endoscopic technique to
      resect selected head and neck cancers. STUDY DESIGN: In total, 13 patients
      underwent TORS procedure for resection of head and neck cancers of various
      localizations, within the ENT Department of Limoges University Hospital Center
      between March and October 2010. RESULTS: Tumor localizations were aryepiglottic
      fold (n = 3), pyriform sinus (n = 2), posterior pharyngeal wall (n = 2), base of
      tongue (n = 2), lateral pharyngeal wall (n = 2), vallecula (n = 1), and
      epiglottis (n = 1). Average TORS setup time was 23 minutes. Average TORS
      operative time was 45 minutes. Average hospital stay was 8.4 days. CONCLUSIONS:
      TORS is a new technique that permits excellent resection of selected head and
      neck cancers with poor morbidity. Future reports on long-term oncologic and
      functional outcomes are needed to assess the risks and benefits of this approach
      compared with external approaches and nonsurgical alternatives.

PMID- 21737467
TI  - PPH-01 versus PPH-03 to perform STARR for the treatment of hemorrhoids associated
      with large internal rectal prolapse: a prospective multicenter randomized trial.
AB  - PURPOSE: This multicenter randomized study was designed to compare the clinical
      and functional results of stapled transanal rectal resection (STARR) performed
      with 2 staplers (PPH-01 vs. PPH-03) in the treatment of hemorrhoidal disease
      associated with a large internal rectal prolapse. METHODS: From a total of 937
      patients, referred for hemorrhoidal disease in the 20 centers involved in the
      study, 425 (45.3%) with prolapsed hemorrhoids associated with a large internal
      rectal prolapse were randomized to undergo STARR with PPH-01 or PPH-03.
      Postoperative evaluation was made at 3, 6, and 12 months. RESULTS: The incidence
      of bleeding at the stapled line was significantly lower in the PPH-03 group than
      in the PPH-01 group (58/207 [28.0%] vs. 145/201 [72.1%]; P < .0001); the mean
      number of hemostatic stitches was significantly higher in the PPH-01 than in the
      PPH-03 group (3.2 +/- 0.1 vs. 1.8 +/- 0.8; P < .0001). The mean operative time
      was 25.1 +/- 11.5 minutes in the PPH-03 group and 38.1 +/- 15.7 minutes in the
      PPH-01 group (P < .0001). No major complications occurred in either of the
      groups. At 12-month follow-up, the success rate in the 2 groups was 94.5% in the
      PPH01 group and 94.2% in the PPH03 group. CONCLUSION: STARR performed for the
      treatment of hemorrhoidal disease associated with a large rectal prolapse is a
      safe and effective procedure. The use of the PPH-03 stapler instead of the PPH-01
      guarantees a statistically significant reduction of intraoperative bleeding and a
      significant decrease of the operative time.

PMID- 21737468
TI  - Diabetic ketoacidosis at the onset of type 1 diabetes.

PMID- 21737469
TI  - Glycaemic control in type 1 diabetes during real time continuous glucose
      monitoring compared with self monitoring of blood glucose: meta-analysis of
      randomised controlled trials using individual patient data.
AB  - OBJECTIVE: To determine the clinical effectiveness of real time continuous
      glucose monitoring compared with self monitoring of blood glucose in type 1
      diabetes. DESIGN: Meta-analysis of randomised controlled trials. DATA SOURCES:
      Cochrane database for randomised controlled trials, Ovid Medline, Embase, Google
      Scholar, lists of papers supplied by manufacturers of continuous glucose
      monitors, and cited literature in retrieved articles. Studies reviewed Randomised
      controlled trials of two or more months' duration in men and non-pregnant women
      with type 1 diabetes that compared real time continuous glucose monitoring with
      self monitoring of blood glucose and where insulin delivery was the same in both
      arms. Analysis Two step meta-analysis of individual patient data with the primary
      outcome of final glycated haemoglobin (HbA(1c)) percentage and area under the
      curve of hypoglycaemia (glucose concentration <3.9 mmol/L) during either
      treatment, followed by one step metaregression exploring patient level
      determinants of HbA(1c) and hypoglycaemia. RESULTS: Six trials were identified,
      consisting of 449 patients randomised to continuous glucose monitoring and 443 to
      self monitoring of blood glucose. The overall mean difference in HbA(1c) for
      continuous glucose monitoring versus self monitoring of blood glucose was -0.30%
      (95% confidence interval -0.43% to -0.17%) (-3.0, -4.3 to -1.7 mmol/mol). A best
      fit regression model of determinants of final HbA(1c) showed that for every one
      day increase of sensor usage per week the effect of continuous glucose monitoring
      versus self monitoring of blood glucose increased by 0.150% (95% credibility
      interval -0.194% to -0.106%) (1.5, -1.9 to -1.1 mmol/mol) and every 1% (10
      mmol/mol) increase in baseline HbA(1c) increased the effect by 0.126% (-0.257% to
      0.0007%) (1.3, -2.6 to 0.0 mmol/mol). The model estimates that, for example, a
      patient using the sensor continuously would experience a reduction in HbA(1c) of
      about 0.9% (9 mmol/mol) when the baseline HbA(1c) is 10% (86 mmol/mol). The
      overall reduction in area under the curve of hypoglycaemia was -0.28 (-0.46 to 
      0.09), corresponding to a reduction in median exposure to hypoglycaemia of 23%
      for continuous glucose monitoring compared with self monitoring of blood glucose.
      In a best fit regression model, baseline area under the curve of hypoglycaemia
      was only weakly related to the effect of continuous glucose monitoring compared
      with self monitoring of blood glucose on hypoglycaemia outcome, and sensor usage
      was unrelated to hypoglycaemia at outcome. CONCLUSIONS: Continuous glucose
      monitoring was associated with a significant reduction in HbA(1c) percentage,
      which was greatest in those with the highest HbA(1c) at baseline and who most
      frequently used the sensors. Exposure to hypoglycaemia was also reduced during
      continuous glucose monitoring. The most cost effective or appropriate use of
      continuous glucose monitoring is likely to be when targeted at people with type 1
      diabetes who have continued poor control during intensified insulin therapy and
      who frequently use continuous glucose monitoring.

PMID- 21737470
TI  - Factors associated with the presence of diabetic ketoacidosis at diagnosis of
      diabetes in children and young adults: a systematic review.
AB  - OBJECTIVE: To identify the factors associated with diabetic ketoacidosis at
      diagnosis of type 1 diabetes in children and young adults. DESIGN: Systematic
      review. DATA SOURCES: PubMed, EMBASE, Web of Science, Scopus, and Cinahl and
      article reference lists. STUDY SELECTION: Cohort studies including unselected
      groups of children and young adults presenting with new onset type 1 diabetes
      that distinguished between those who presented in diabetic ketoacidosis and those
      who did not and included a measurement of either pH or bicarbonate in the
      definition of diabetic ketoacidosis. There were no restrictions on language of
      publication. RESULTS: 46 studies involving more than 24,000 children in 31
      countries were included. Together they compared 23 different factors. Factors
      associated with increased risk were younger age (for <2 years old v older, odds
      ratio 3.41 (95% confidence interval 2.54 to 4.59), for <5 years v older, odds
      ratio 1.59 (1.38 to 1.84)), diagnostic error (odds ratio 3.35 (2.35 to 4.79)),
      ethnic minority, lack of health insurance in the US (odds ratio 3.20 (2.03 to
      5.04)), lower body mass index, preceding infection (odds ratio 3.14 (0.94 to
      10.47)), and delayed treatment (odds ratio 1.74 (1.10 to 2.77)). Protective
      factors were having a first degree relative with type 1 diabetes at the time of
      diagnosis (odds ratio 0.33 (0.08 to 1.26)), higher parental education (odds
      ratios 0.4 (0.20 to 0.79) and 0.64 (0.43 to 0.94) in two studies), and higher
      background incidence of type 1 diabetes (correlation coefficient -0.715). The
      mean duration of symptoms was similar between children presenting with or without
      diabetic ketoacidosis (16.5 days (standard error 6.2) and 17.1 days (6.0)
      respectively), and up to 38.8% (285/735) of children who presented with diabetic
      ketoacidosis had been seen at least once by a doctor before diagnosis.
      CONCLUSIONS: Multiple factors affect the risk of developing diabetic ketoacidosis
      at the onset of type 1 diabetes in children and young adults, and there is
      potential time, scope, and opportunity to intervene between symptom onset and
      development of diabetic ketoacidosis for both parents and clinicians.

PMID- 21737473
TI  - World's most vulnerable are being left behind in efforts to reach millennium
      development goals, says UN chief.

PMID- 21737471
TI  - Payment reform needed to promote integrated care, says Nuffield Trust.

PMID- 21737474
TI  - Grand challenges in mental health are identified.

PMID- 21737477
TI  - Estimating the proportion of Danes at high risk of fatal cardiovascular disease.
AB  - AIMS: It has been recommended by several intervention studies to use a high risk
      approach for cardiovascular disease (CVD) prevention, and the European Guidelines
      on Cardiovascular Disease Prevention in Clinical Practice (ESC Guidelines)
      provide a method to identify high risk individuals. Furthermore the ESC
      Guidelines suggest interventions for the high risk group, with the overall
      intention to reduce CVD mortality. The ESC Guidelines have not yet been applied
      in cardiovascular research in Denmark. Therefore, the aim of this study is to
      estimate the proportion at high risk for fatal CVD in a Danish population.
      METHODS: Data from a population-based cross-sectional study from the Research
      Centre for Prevention and Health (the former Glostrup Population Studies) from
      2006 was used. A total of 2,815 individuals aged 25-64 years were included in the
      analysis. The criteria listed in ESC Guidelines were used to identify the high
      risk group. The results were stratified according to age and sex. RESULTS: A
      total of 21.2% were categorized as high risk for fatal CVD, and 51.6% of the high
      risk individuals were categorized due to a SCORE risk >= 5%. In general more men
      than women were categorized as high risk within the different age groups. A
      larger proportion was categorized in high risk in the oldest age groups compared
      with the younger ones. CONCLUSIONS: With the considerably large proportion at
      high risk -one in five individuals - it is worthwhile considering increasing the
      attention given to identify high risk individuals. Applying the interventions
      suggested in the ESC Guidelines to high risk individuals could potentially reduce
      CVD mortality in Denmark.

PMID- 21737478
TI  - WHO urges more countries to adopt large graphic health warnings on tobacco
      products.

PMID- 21737479
TI  - Drug interactions in palliative care--it's more than cytochrome P450.
AB  - OBJECTIVE: This study aims to identify the combination of substances with high
      potential for drug interactions in a palliative care setting and to provide
      concise recommendations for physicians. METHODS: We used a retrospective
      systematic chart analysis of 200 consecutive inpatients. The recently developed
      and internationally advocated classification system OpeRational ClAssification of
      Drug Interactions was applied using the national database of the Federal Union of
      German Associations of Pharmacists. Charts of patients with potential for severe
      DDIs were examined manually for clinical relevance. RESULTS: In 151 patients
      (75%) a total of 631 potential drug interactions were identified. Opioids
      (exception: methadone), non-opioids (exception: non-steroidal anti-inflammatory
      drugs), benzodiazepines, proton-pump inhibitors, laxatives, co-analgesics
      (exception: carbamazepine) and butylscopolamine were generally safe. High
      potential for drug interactions included combinations of scopolamine,
      neuroleptics, metoclopramide, antihistamines, non-steroidal anti-inflammatory
      drugs, (levo-) methadone, amitriptyline, carbamazepine and diuretics. The manual
      analyses of records from eight patients with risk for severe drug interactions
      provided no indicator for clinical relevance in these specific patients. Drug
      interactions attributed to the cytochrome pathway played a minor role (exception:
      carbamazepine). CONCLUSION: Most relevant drug interactions can be expected with:
      (i) drugs (inter-) acting via histamine, acetylcholine or dopamine receptors; and
      (ii) Non-steroidal anti-inflammatory drugs. Even in last hours of life the
      combination of substances (e.g. anticholinergics) may produce relevant drug
      interactions (e.g. delirium). PERSPECTIVE: Data on the potential for drug-drug
      interactions in palliative case is extremely scarce, but drug interactions can be
      limited if a few facts are considered. A synopsis of the findings of these
      studies is presented as concise recommendation to minimize drug interactions.

PMID- 21737480
TI  - Developing a national quality register in end-of-life care: the Swedish
      experience.
AB  - BACKGROUND: The complexity of end-of-life care, represented by a large number of
      units caring for dying patients, different types of organizations and
      difficulties in identification and prognostication, signifies the importance of
      finding ways to measure the quality of end-of-life care. AIM: To establish, test
      and manage a national quality register for end-of-life care. DESIGN: Two
      questionnaires were developed with an attempt to retrospectively identify
      important aspects of the care delivered during the last week in life. An internet
      based IT platform was created, enabling the physician and/or nurse responsible
      for the care during the last week in life to register answers online. SETTING:
      Units caring for dying people, such as hospital wards, home care units,
      palliative in-patient care units and nursing facilities. RESULTS: The register
      received status as a National Quality Register in 2006. More than 30,000 deaths
      in nursing facilities, hospital wards, palliative in-patient units and private
      homes were registered during 2010, representing 34% of all deaths in Sweden and
      58% of the cancer deaths. CONCLUSIONS: We have shown that it is feasible to
      establish a national quality register in end-of-life care and collect data
      through a web-based system. Ongoing data analyses will show in what way this
      initiative can lead to improved quality of life for patients and their families.
      There is an ongoing process internationally to define relevant outcome measures
      for quality of care at the end-of-life in different care settings; the registry
      has a potentially important role in this development.

PMID- 21737481
TI  - How can informal caregivers in cancer and palliative care be supported? An
      updated systematic literature review of interventions and their effectiveness.
AB  - INTRODUCTION: Informal caregivers needs in cancer/advanced disease are largely
      unmet. The science of carer intervention evaluation is methodologically
      challenging, and the evidence historically weak. OBJECTIVE: This systematic
      review updates an earlier effectiveness review to determine both the
      effectiveness of subsequently published intervention studies, and the current
      state of science. METHOD: The evidence was identified and appraised using a
      comprehensive search strategy. Articles were searched from 2001 to 2010 using the
      following electronic databases: Medline, PsychINFO and CINAHL. Inclusion criteria
      were studies reporting intervention data for informal adult caregivers of a
      patient with a diagnosis of cancer or receiving palliative care. The design and
      evidence rigour were assessed using the Jadad Rating Scale, and the Quality
      Rating Scale. RESULTS: 33 studies met inclusion criteria. From the original
      review, an encouraging increase was identified in the number of evaluations (from
      8 to 33), in carer-specific interventions (from 6 to 17) and in the robustness of
      the study design (an increase from 2 to 12 studies with before/after measures,
      comparison groups and prospective data). CONCLUSIONS: The evidence suggests a
      rapid increase in the number of robust intervention studies. However, the range
      of models remains narrow in relation to caregivers' needs and preferences.

PMID- 21737482
TI  - Pain and distress in advanced dementia: choosing the right tools for the job.
AB  - OBJECTIVE: There is a concern that pain is under-recognized in dementia. However,
      there may be other causes of distress. We wished to evaluate the utility of a
      distress tool and a pain tool. METHODS: Nursing home residents with advanced
      dementia were observed using pain (Pain Assessment in Advanced Dementia scale
      (PAINAD)) and distress (Disability Distress Assessment Tool (DisDAT)) assessment
      tools. Those in pain were treated. Reassessment occurred at one and three months.
      RESULTS: From 79 participants, 13 were assessed as being in pain. Psychosocial
      factors explained the behaviour of a false positive group. Both tools showed a
      significant decrease in pain following intervention (p = 0.008). Behaviours were
      similar in both groups. CONCLUSIONS: Both tools are useful. However, the pain
      tool also picks up distress, which is not caused by pain. It could potentially
      lead to false ascriptions of pain. The distress tool picks up a broader array of
      signs, which may be useful both in practice and in research.

PMID- 21737483
TI  - Red light, Phot1 and JAC1 modulate Phot2-dependent reorganization of chloroplast
      actin filaments and chloroplast avoidance movement.
AB  - The phototropin (phot)-dependent intracellular relocation of chloroplasts is a
      ubiquitous phenomenon in plants. We have previously revealed the involvement of a
      short cp-actin (chloroplast actin) filament-based mechanism in this movement.
      Here, the reorganization of cp-actin filaments during the avoidance movement of
      chloroplasts was analyzed in higher time resolution under blue GFP (green
      fluorescent protein) excitation light in an actin filament-visualized line of
      Arabidopsis thaliana. Under standard background red light of 89 MUmol m(-2) s(
      1), cp-actin filaments transiently disappeared at approximately 30 s and
      reappeared in a biased configuration on chloroplasts approximately 70 s after
      blue excitation light irradiation. The timing of biased cp-actin reappearance was
      delayed under the background of strong red light or in the absence of red light.
      Consistently, chloroplast movement was delayed under these conditions. In phot1
      mutants, acceleration of both the disappearance and reappearance of cp-actin
      filaments occurred, indicating an inhibitory action of phot1 on reorganization of
      cp-actin filaments. Avoidance movements began sooner in phot1 than in wild-type
      plants. No reorganization of cp-actin filaments was seen in phot2 or phot1phot2
      mutants lacking phot2, which is responsible for avoidance movements.
      Surprisingly, jac1 (j-domain protein required for chloroplast accumulation
      response 1) mutants, lacking the accumulation response, showed no avoidance
      movements under the whole-cell irradiation condition for GFP observation. Cp
      actin filaments in jac1 did not show a biased distribution, with a small or
      almost no transient decrease in the number. These results indicate a close
      association between the biased distribution of cp-actin filaments and chloroplast
      movement. Further, JAC1 is suggested to function in the biased cp-actin filament
      distribution by regulating their appearance and disappearance.

PMID- 21737484
TI  - Long-range epigenetic silencing associates with deregulation of Ikaros targets in
      colorectal cancer cells.
AB  - Transcription factors are common targets of epigenetic inactivation in human
      cancer. Promoter hypermethylation and subsequent silencing of transcription
      factors can lead to further deregulation of their targets. In this study, we
      explored the potential epigenetic deregulation in cancer of Ikaros family genes,
      which code for essential transcription factors in cell differentiation and
      exhibit genetic defects in hematologic neoplasias. Unexpectedly, our analysis
      revealed that Ikaros undergoes very specific promoter hypermethylation in
      colorectal cancer, including in all the cell lines studied and around 64% of
      primary colorectal adenocarcinomas, with increasing proportions in advanced
      Duke's stages. Ikaros hypermethylation occurred in the context of a novel long
      range epigenetic silencing (LRES) region. Reintroduction of Ikaros in colorectal
      cancer cells, ChIP-chip analysis, and validation in primary samples led us to
      identify a number of direct targets that are possibly related with colorectal
      cancer progression. Our results not only provide the first evidence that LRES can
      have functional specific effects in cancer but also identify several deregulated
      Ikaros targets that may contribute to progression in colorectal adenocarcinoma.

PMID- 21737485
TI  - Pilot assessment of the antineoplastic drug contamination levels in British
      Columbian hospitals pre- and post-cleaning.
AB  - OBJECTIVE: We undertook a pilot study involving six British Columbian hospital
      pharmacies to determine if antineoplastic drug contamination of surfaces exists
      and whether residual drugs remain on these surfaces despite being cleaned.
      METHODS: At each site, the pharmacy technician responsible for preparing the
      antineoplastic drugs was observed to determine which surfaces were contacted and
      to ascertain the frequency of contact. Surfaces observed to be most frequently
      contacted were subsequently wiped after drug preparation pre- and post-clean. The
      wipe samples were then analyzed by liquid chromatography tandem mass spectrometry
      to determine the amount of contamination. Cyclophosphamide (CP) and methotrexate
      (MTX) were used as representative markers to reflect overall antineoplastic drug
      contamination levels. RESULTS: Fourteen of the 23 surfaces sampled pre-clean
      (61%) were contaminated with either MTX or CP. The pre-clean wipe samples had a
      geometric mean concentration of 0.0135 ng/cm(2) for MTX (range <Limit of
      Detection {LOD} to 12.45 ng/cm(2)) and 0.114 ng/cm(2) for CP (range <LOD to 8.53
      ng/cm(2)). Post-clean contamination levels were generally lower than its pre
      clean equivalent; the concentration difference post- vs. pre-clean was
      statistically significant for CP only. However, some samples appeared to have
      higher post-clean contamination levels. CONCLUSIONS: The results suggest that
      drug contamination is common in hospital pharmacies we sampled and that current
      cleaning practices in British Columbia may not be effective in removing residual
      drug from the surfaces. A more extensive study is recommended to confirm these
      results as well as a review of cleaning protocols to ensure their effectiveness
      in reducing contamination levels.

PMID- 21737486
TI  - Impact of trandolapril therapy and its combination with a calcium channel blocker
      on plasma adiponectin levels in patients with type 2 diabetes and hypertension.
AB  - INTRODUCTION: Adiponectin is secreted from adipose tissue and exhibits a
      protective effect against cardiovascular disease; plasma adiponectin
      concentrations are decreased in type 2 diabetic and in hypertensive patients.
      OBJECTIVE: The aim of this study was to compare the effect of trandolapril (T)
      and its fixed-dose combination with verapamil (FDTV) on adiponectin levels in
      hypertensive type 2 diabetic patients. METHODS: A total of 40 type 2 diabetic
      patients with never-treated hypertension were randomly assigned to two groups.
      One group received FDTV 180 mg + T 2 mg, once a day; the other group received T 2
      mg once a day, administered for 3 months in both groups. Adiponectin was measured
      by enzyme-linked immunosorbent assay (ELISA) at the beginning and end of the
      study. Patients were evaluated monthly for blood pressure, fasting serum glucose
      and adverse events. Statistical analysis was performed with analysis of variance
      (ANOVA). RESULTS: All patients experienced a significant reduction of blood
      pressure. Both therapeutics regimens increased the levels of adiponectin,
      However, FDTV produces a higher increase in the levels of the hormone (8.15 +/-
      4.6 to 10.96 +/- 5.6 ug/ml) when compared with the T treatment (7.64 +/- 3.8 to
      8.92 +/- 4.4 ug/ml), p < 0.05. None of the patients suffered adverse events.
      CONCLUSION: Our results show that the addition of FDTV to T produced a greater
      increase on adiponectin levels than trandolapril alone.

PMID- 21737487
TI  - microRNA-associated progression pathways and potential therapeutic targets
      identified by integrated mRNA and microRNA expression profiling in breast cancer.
AB  - microRNA expression profiling plays an emerging role in cancer classification and
      identification of therapeutic strategies. In this study, we have evaluated the
      benefits of a joint microRNA-mRNA analysis in breast cancer. Matched mRNA and
      microRNA global expression profiling was conducted in a well-annotated cohort of
      207 cases with complete 10-year follow-up. Penalized Cox regression including
      microRNA expression, mRNA expression, and clinical covariates was used to
      identify microRNAs associated with distant relapse-free survival (DRFS) that
      provide independent prognostic information, and are not simply surrogates of
      previously identified prognostic covariates. Penalized regression was chosen to
      prevent overfitting. Furthermore, microRNA-mRNA relationships were explored by
      global expression analysis, and exploited to validate results in several
      published cohorts (n = 592 with DRFS, n = 1,050 with recurrence-free survival).
      Four microRNAs were independently associated with DRFS in estrogen receptor (ER)
      positive (3 novel and 1 known; miR-128a) and 6 in ER-negative (5 novel and 1
      known; miR-210) cases. Of the latter, miR-342, -27b, and -150 were prognostic
      also in triple receptor-negative tumors. Coordinated expression of predicted
      target genes and prognostic microRNAs strengthened these results, most
      significantly for miR-210, -128a, and -27b, whose targets were prognostic in meta
      analysis of several cohorts. In addition, miR-210 and -128a showed coordinated
      expression with their cognate pri-microRNAs, which were themselves prognostic in
      independent cohorts. Our integrated microRNA-mRNA global profiling approach has
      identified microRNAs independently associated with prognosis in breast cancer.
      Furthermore, it has validated known and predicted microRNA-target interactions,
      and elucidated their association with key pathways that could represent novel
      therapeutic targets.

PMID- 21737488
TI  - Clusterin inhibition using OGX-011 synergistically enhances Hsp90 inhibitor
      activity by suppressing the heat shock response in castrate-resistant prostate
      cancer.
AB  - Small-molecule inhibitors of Hsp90 show promise in the treatment of castrate
      resistant prostate cancer (CRPC); however, these inhibitors trigger a heat shock
      response that attenuates drug effectiveness. Attenuation is associated with
      increased expression of Hsp90, Hsp70, Hsp27, and clusterin (CLU) that mediate
      tumor cell survival and treatment resistance. We hypothesized that preventing CLU
      induction in this response would enhance Hsp90 inhibitor-induced CRPC cell death
      in vitro and in vivo. To test this hypothesis, we treated CRPC with the Hsp90
      inhibitor PF-04929113 or 17-AAG in the absence or presence of OGX-011, an
      antisense drug that targets CLU. Treatment with either Hsp90 inhibitor alone
      increased nuclear translocation and transcriptional activity of the heat shock
      factor HSF-1, which stimulated dose- and time-dependent increases in HSP
      expression, especially CLU expression. Treatment-induced increases in CLU were
      blocked by OGX-011, which synergistically enhanced the activity of Hsp90
      inhibition on CRPC cell growth and apoptosis. Accompanying these effects was a
      decrease in HSF-1 transcriptional activity as well as expression of HSPs, Akt,
      prostate-specific antigen, and androgen receptor. In vivo evaluation of the Hsp90
      inhibitors with OGX-011 in xenograft models of human CRPC showed that OGX-011
      markedly potentiated antitumor efficacy, leading to an 80% inhibition of tumor
      growth with prolonged survival compared with Hsp90 inhibitor monotherapy.
      Together, our findings indicate that Hsp90 inhibitor-induced activation of the
      heat shock response and CLU is attenuated by OGX-011, with synergistic effects on
      delaying CRPC progression.

PMID- 21737489
TI  - Pericardial fat is associated with impaired lung function and a restrictive lung
      pattern in adults: the Jackson Heart Study.
AB  - BACKGROUND: Impaired lung function has been linked to obesity and systemic
      inflammation. Pericardial fat has been shown to be associated with anomalies in
      cardiac structure, function, and atherosclerosis. We hypothesized that
      pericardial fat may have a similar role in the impairment of lung function.
      METHODS: Cross-sectional associations of pericardial fat volumes, quantified by
      multidetector CT scan, with FEV(1) and FVC assessed by spirometry, were
      investigated in 1,293 participants (54.5 +/- 10.8 years; 66.4% women) in the
      Jackson Heart Study. We also examined whether these associations were independent
      of visceral adipose tissue (VAT). RESULTS: Pericardial fat was associated with
      impaired lung function after multivariable adjustment, but these associations
      generally did not remain after adjustment for VAT. An exception was the
      FEV(1)/FVC ratio. Higher pericardial fat volumes were associated with higher odds
      of a restrictive lung pattern and lower odds of airway obstruction. Participants
      in the highest quartile had the highest odds of a restrictive lung pattern (OR,
      1.85; 95% CI, 1.22-2.79, compared with quartile 1), even after adjustment for
      VAT. The odds of obstruction decreased across increasing quartiles of pericardial
      fat. These relationships were generally graded, suggesting dose-response trends.
      CONCLUSIONS: Pericardial fat is generally associated with lower lung function and
      independently associated with a restrictive lung pattern in middle-aged and
      elderly adults. Further research is needed to fully understand the mechanisms
      through which pericardial fat contributes to pulmonary anomalies.

PMID- 21737490
TI  - Measuring a change in self-efficacy following pulmonary rehabilitation: an
      evaluation of the PRAISE tool.
AB  - BACKGROUND: Self-efficacy explores the emotional functioning and coping skills of
      an individual and is thought to be a strong predictor of health behaviors, which
      is particularly important for pulmonary rehabilitation (PR). However, to our
      knowledge, there is no measure of self-efficacy developed to explore behavior
      change in the context of PR. METHODS: We investigated the reproducibility and
      sensitivity of Pulmonary Rehabilitation Adapted Index of Self-Efficacy (PRAISE):
      a tool adapted from the General Self-Efficacy Scale (GSES) to measure the
      dimension of self-efficacy at the time of a course of PR. Twenty-nine clinically
      stable patients with COPD completed PRAISE on their initial assessment to PR. The
      tool was then completed 7 days later. An additional 225 patients completed PRAISE
      prior to, and on completion of a 7-week course of PR. In addition, exercise
      capacity was measured by the incremental shuttle walk test (ISWT), with the
      Medical Research Council (MRC) dyspnea scale, Chronic Respiratory Questionnaire
      Self Reported (CRQ-SR), and Hospital Anxiety and Depression Scale (HADS) also
      being collected. This process was repeated postrehabilitation. Data were then
      analyzed to investigate the possibility that PRAISE could be an indicator of PR
      response. RESULTS: In the reproducibility study, the mean change in score was
      0.72 (95% CI, -2.27-0.82), examined with intraclass correlation coefficients, r =
      0.99; indicating PRAISE test-retest reproducibility. The mean change of score in
      the sensitivity study pre- to post-PR was 3.59 (95% CI, 2.24-4.73; P = .015).
      Change in the ISWT was 83.44 m (95% CI, 54.0-112.8; P < .0001). There were
      several statistically significant differences between variables, particularly
      with the mastery and emotion elements of the CRQ-SR at baseline, but this was
      lost post-PR. This observation was also found with HADS. No significant
      differences were found between MRC dypsnea scale grades with the change in PRAISE
      score. PRAISE could not predict a successful outcome of PR. CONCLUSIONS: The
      PRAISE tool is a reliable and sensitive measure of self-efficacy for patients
      with COPD attending PR.

PMID- 21737491
TI  - The effect of clinical covariates on the diagnostic and prognostic value of
      soluble mesothelin and megakaryocyte potentiating factor.
AB  - BACKGROUND: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF)
      are serum biomarkers of mesothelioma. This study examined the effect of clinical
      covariates on biomarkers levels and their diagnostic and prognostic value.
      METHODS: Five hundred ninety-four participants were enrolled in a multicenter
      study, including 106 patients with mesothelioma and 488 control subjects.
      Multiple linear regression analyses were used to identify which covariates were
      independently associated with SM and MPF levels. The effect of these covariates
      on the diagnostic accuracy was evaluated with receiver operating characteristics
      curve analysis. In patients with mesothelioma, survival analysis was performed
      with Cox regression. RESULTS: SM and MPF levels were independently associated
      with age, glomerular filtration rate (GFR), and BMI in control subjects and with
      GFR and tumor stage in patients with mesothelioma. The diagnostic accuracy of SM
      and MPF was significantly affected by the distribution of these covariates in the
      study population. The patients with mesothelioma were best discriminated from the
      control subjects with either the youngest age, the highest GFR, or the largest
      BMI. Furthermore, the control subjects were significantly better differentiated
      from stage II to IV than from stage I mesothelioma. MPF, not SM, was an
      independent negative prognostic factor, but only if adjusted for the biomarker
      associated covariates. CONCLUSIONS: SM and MPF levels were affected by the same
      clinical covariates, which also had a significant impact on their diagnostic and
      prognostic value. To improve the interpretation of biomarker results, age, GFR,
      and BMI should be routinely recorded. Approaches to account for these covariates
      require further validation, as does the prognostic value of SM and MPF.

PMID- 21737492
TI  - Hemophagocytic lymphohistiocytosis: a potentially underrecognized association
      with systemic inflammatory response syndrome, severe sepsis, and septic shock in
      adults.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) was originally described as
      a genetic disorder of immune regulation, presenting in neonates with protracted
      fever, hepatosplenomegaly, and cytopenia. A secondary form of HLH, triggered by
      serious infections, was subsequently described in adults. METHODS: We report
      three adult patients who presented with systemic inflammatory response syndrome
      and features consistent with severe sepsis and septic shock, who subsequently
      received a diagnosis of secondary HLH. We reviewed the relationship between
      infection-triggered HLH and septic shock from the perspective of the adult
      intensivist. RESULTS: The hyperinflammatory pathophysiologic characteristics of
      HLH and septic shock are closely intertwined. Clinical and laboratory features of
      HLH and septic shock overlap in some patients, making the syndromes difficult to
      distinguish. In our experience and review, progressive pancytopenia was the
      feature most likely to suggest secondary HLH in the adult patient with presumed
      (or definite) septic shock. Use of other HLH-2004 diagnostic criteria is hindered
      by the poor operating characteristics of these tests in critically ill adults.
      Bone marrow aspiration is the most useful diagnostic test, but may yield an
      initial false-negative result. CONCLUSION: The HLH-2004 treatment protocol is not
      of proven benefit in critically ill adults, but observational data suggest that
      aggressive immunosuppressive therapy should not be delayed. Further study of HLH
      in the critical care setting might provide important insights into the
      pathogenesis and clinical treatment of sepsis.

PMID- 21737493
TI  - Management of cardiac sarcoidosis in the United States: a Delphi study.
AB  - BACKGROUND: No formal guidelines exist to guide physicians caring for patients
      with sarcoidosis in their screening for management of patients with cardiac
      sarcoidosis. We conducted a modified Delphi study to investigate if a consensus
      could be reached on the best approaches for screening for and management of
      cardiac sarcoidosis. METHODS: A modified Delphi study design with two rounds of
      questionnaires was used to investigate if a consensus existed among sarcoid
      experts in the United States on the best management approaches for cardiac
      sarcoidosis. Experts were identified based on their national reputation as
      sarcoid experts and by being actively involved in sarcoidosis clinics at their
      institutions. RESULTS: Overall agreement was low to moderate. Agreement was
      reached on the role of history, physical examination, and 12-lead ECG in
      screening, echocardiogram, Holter monitor, myocardial fluorodeoxyglucose PET
      scan, and cardiac MRI in workup, and steroids in treatment. Agreement was not
      reached on the role of signal-averaged ECG in screening, optimum dose of
      prednisone, use of steroid-sparing agents, and duration of treatment. Several
      comments underscore the diverse approaches and uncertainty that exist in managing
      cardiac sarcoidosis. CONCLUSIONS: Our study highlights the dilemma that sarcoid
      experts face in their approach to cardiac sarcoidosis. It also highlights the
      lack of agreement among sarcoid experts on key aspects of diagnosis and
      management and stresses the importance of collaborative efforts to investigate
      the best strategies for screening for and management of cardiac sarcoidosis.

PMID- 21737494
TI  - Frequency of undiagnosed cystic lung disease in patients with sporadic renal
      angiomyolipomas.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of undiagnosed
      cystic lung lesions suggestive of pulmonary lymphangioleiomyomatosis (LAM) in
      patients who received a diagnosis of sporadic renal angiomyolipomas (AMLs).
      METHODS: We conducted a retrospective review of CT scans of the chest or abdomen
      for cystic lung lesions on 176 adult patients who received a diagnosis of
      sporadic renal AML during a 10-year period, 1997 to 2006, and comparison with
      chest CT scans of 176 control subjects without renal AML but matched for age,
      sex, and smoking history. Patients presenting with suspected or known pulmonary
      LAM and those with underlying tuberous sclerosis were excluded. RESULTS: Sporadic
      renal AML was diagnosed in 176 patients with a median age of 58 years (range, 20
      91 years), the majority of whom were women (81.8%). Renal tumor was an incidental
      finding on imaging studies for most patients (90.3%). Nineteen patients (10.8%)
      had one or more cystic lung lesions and included nine patients (5.1%) with four
      or more cysts, all of whom were women. In comparison, eight control subjects
      (4.6%) had one to three cystic lung lesions and none of them exhibited four or
      more cysts. None of the patients with renal AML and cystic lung lesions,
      including six women with 10 or more cysts, had undergone an evaluation of their
      cystic lung disease. CONCLUSIONS: We conclude that a significant portion of women
      with sporadic renal AMLs exhibit cystic lung lesions suggestive of pulmonary LAM
      but may remain undiagnosed. Coexistence of pulmonary LAM should be considered in
      women incidentally found to have sporadic renal AMLs.

PMID- 21737495
TI  - Gentisate 1,2-dioxygenase, in the third naphthalene catabolic gene cluster of
      Polaromonas naphthalenivorans CJ2, has a role in naphthalene degradation.
AB  - Polaromonas naphthalenivorans strain CJ2 metabolizes naphthalene via the
      gentisate pathway and has recently been shown to carry a third copy of gentisate
      1,2-dioxygenase (GDO), encoded by nagI3, within a previously uncharacterized
      naphthalene catabolic gene cluster. The role of this cluster (especially nagI3)
      in naphthalene metabolism of strain CJ2 was investigated by documenting patterns
      in regulation, transcription and enzyme activity. Transcriptional analysis of
      wild-type cells showed the third cluster to be polycistronic and that nagI3 was
      expressed at a relatively high level. Individual knockout mutants of all three
      nagI genes were constructed and their influence on both GDO activity and cell
      growth was evaluated. Of the three knockout strains, CJ2DeltanagI3 showed
      severely diminished GDO activity and grew slowest on aromatic substrates. These
      observations are consistent with the hypothesis that nagI3 may prevent toxic
      intracellular levels of gentisate from accumulating in CJ2 cells. All three nagI
      genes from strain CJ2 were cloned into Escherichia coli: the nagI2 and nagI3
      genes were successfully overexpressed. The subunit mass of the GDOs were ~36-39
      kDa, and their structures were deduced to be dimeric. The K(m) values of NagI2
      and NagI3 were 31 and 10 uM, respectively, indicating that the higher affinity of
      NagI3 for gentisate may protect the wild-type cells from gentisate toxicity.
      These results provide clues for explaining why the third gene cluster,
      particularly the nagI3 gene, is important in strain CJ2. The organization of
      genes in the third gene cluster matched that of clusters in Polaromonas sp. JS666
      and Leptothrix cholodnii SP-6. While horizontal gene transfer (HGT) is one
      hypothesis for explaining this genetic motif, gene duplication within the
      ancestral lineage is equally valid. The HGT hypothesis was discounted by noting
      that the nagI3 allele of strain CJ2 did not share high sequence identity with its
      homologues in Polaromonas sp. JS666 and L. cholodnii SP-6.

PMID- 21737496
TI  - An optimized in vitro blood-brain barrier model reveals bidirectional
      transmigration of African trypanosome strains.
AB  - The transmigration of African trypanosomes across the human blood-brain barrier
      (BBB) is the critical step during the course of human African trypanosomiasis.
      The parasites Trypanosoma brucei gambiense and T. b. rhodesiense are transmitted
      to humans during the bite of tsetse flies. Trypanosomes multiply within the
      bloodstream and finally invade the central nervous system (CNS), which leads to
      the death of untreated patients. This project focused on the mechanisms of
      trypanosomal traversal across the BBB. In order to establish a suitable in vitro
      BBB model for parasite transmigration, different human cell lines were used,
      including ECV304, HBMEC and HUVEC, as well as C6 rat astrocytes. Validation of
      the BBB models with Escherichia coli HB101 and E. coli K1 revealed that a
      combination of ECV304 cells seeded on Matrigel as a semi-synthetic basement
      membrane and C6 astrocytes resulted in an optimal BBB model system. The BBB model
      showed selective permeability for the pathogenic E. coli K1 strain, and African
      trypanosomes were able to traverse the optimized ECV304-C6 BBB efficiently.
      Furthermore, coincubation indicated that paracellular macrophage transmigration
      does not facilitate trypanosomal BBB traversal. An inverse assembly of the BBB
      model demonstrated that trypanosomes were also able to transmigrate the optimized
      ECV304-C6 BBB backwards, indicating the relevance of the CNS as a possible
      reservoir of a relapsing parasitaemia.

PMID- 21737497
TI  - Interaction between poly(3-hydroxybutyrate) granule-associated proteins as
      revealed by two-hybrid analysis and identification of a new phasin in Ralstonia
      eutropha H16.
AB  - A large number of polypeptides are attached to poly(3-hydroxybutyrate) (PHB)
      granules of Ralstonia eutropha, such as PHB synthase (PhaC1), several PHB
      depolymerases (PhaZs) and phasins (PhaPs), the regulator protein PhaR(Reu), and
      possibly others. In this study we used the bacterial adenylate cyclase-based two
      hybrid assay to investigate interactions between known PHB granule-associated
      proteins (PGAPs) and to screen for new PGAPs. The utility of the system was
      tested by the in vivo verification of previously postulated interactions of the
      PHB synthase subunits of R. eutropha (PhaC1 homo-oligomerization) and of Bacillus
      megaterium (PhaC(Bmeg)-PhaR(Bmeg) hetero-oligomerization). Nine proteins (PhaA,
      PhaB1, PhaC1, PhaP1-PhaP4, PhaZ1 and PhaR), with established functions in PHB
      metabolism of R. eutropha, were tested for interaction in all combinations. While
      no significant interaction was detected between the PHB synthase PhaC1 and any of
      the other eight tested Pha proteins, strong interactions were found between all
      phasin proteins, in particular between PhaP2 and PhaP4. When PhaP2 was used as
      bait in a two-hybrid screening experiment with a genomic library of R. eutropha,
      the B1934 gene product was identified in 24 out of 53 isolated clones. B1934
      encodes a hypothetical protein (15.7 kDa) with similarity to phasins of PHB
      accumulating bacteria. A fusion protein of eYfp and the B1934 gene product
      colocalized with PHB granules, confirming that B1934 represents a new phasin
      (PhaP5). PhaP5 was not essential for PHB granule formation, but overexpression of
      PhaP5 increased the number of cells with PHB granules at the cell poles.

PMID- 21737498
TI  - Characterization of the role of the RadS/RadR two-component system in the
      radiation resistance of Deinococcus radiodurans.
AB  - Deinococcus radiodurans shows extraordinary tolerance to DNA damage, and exhibits
      differential gene expression and protein recycling. A putative response
      regulator, the DRB0091 (RadR) ORF, was identified from a pool of DNA-binding
      proteins induced in response to gamma radiation in this bacterium. radR is
      located upstream of drB0090, which encodes a putative sensor histidine kinase
      (RadS) on the megaplasmid. Deletion of these genes both individually and together
      resulted in hypersensitivity to DNA-damaging agents and a delayed or altered
      double-strand break repair. A DeltaradRradS double mutant and a DeltaradR single
      mutant showed nearly identical responses to gamma radiation and UVC. Wild-type
      RadR and RadS complemented the corresponding mutant strains, but also exhibited
      significant cross-complementation, albeit at lower doses of gamma radiation. The
      radS transcript was not detected in the DeltaradR mutant, suggesting the
      existence of a radRS operon. Recombinant RadS was autophosphorylated and could
      catalyse the transfer of gamma phosphate from ATP to RadR in vitro. These results
      indicated the functional interaction of RadS and RadR, and suggested a role for
      the RadS/RadR two-component system in the radiation resistance of this bacterium.

PMID- 21737499
TI  - Aeromonas hydrophila motY is essential for polar flagellum function, and requires
      coordinate expression of motX and Pom proteins.
AB  - By the analysis of the Aeromonas hydrophila ATCC7966(T) genome we identified A.
      hydrophila AH-3 MotY. A. hydrophila MotY, like MotX, is essential for the polar
      flagellum function energized by an electrochemical potential of Na(+) as coupling
      ion, but is not involved in lateral flagella function energized by the proton
      motive force. Thus, the A. hydrophila polar flagellum stator is a complex
      integrated by two essential proteins, MotX and MotY, which interact with one of
      two redundant pairs of proteins, PomAB and PomA(2)B(2). In an A. hydrophila motX
      mutant, polar flagellum motility is restored by motX complementation, but the
      ability of the A. hydrophila motY mutant to swim is not restored by introduction
      of the wild-type motY alone. However, its polar flagellum motility is restored
      when motX and -Y are expressed together from the same plasmid promoter. Finally,
      even though both the redundant A. hydrophila polar flagellum stators, PomAB and
      PomA(2)B(2), are energized by the Na(+) ion, they cannot be exchanged.
      Furthermore, Vibrio parahaemolyticus PomAB and Pseudomonas aeruginosa MotAB or
      MotCD are unable to restore swimming motility in A. hydrophila polar flagellum
      stator mutants.

PMID- 21737500
TI  - Altered protein secretion of Chlamydia trachomatis in persistently infected human
      endocervical epithelial cells.
AB  - Chlamydia trachomatis is the most common bacterial infection of the human
      reproductive tract globally; however, the mechanisms underlying the adaptation of
      the organism to its natural target cells, human endocervical epithelial cells,
      are not clearly understood. To secure its intracellular niche, C. trachomatis
      must modulate the host cellular machinery by secreting virulence factors into the
      host cytosol to facilitate bacterial growth and survival. Here we used primary
      human endocervical epithelial cells and HeLa cells infected with C. trachomatis
      to examine the secretion of bacterial proteins during productive growth and
      persistent growth induced by ampicillin. Specifically, we observed a decrease in
      secretable chlamydial protease-like activity factor (CPAF) in the cytosol of host
      epithelial cells exposed to ampicillin with no evident reduction of CPAF product
      by C. trachomatis. In contrast, the expression of CopN and Tarp was
      downregulated, suggesting that C. trachomatis responds to ampicillin exposure by
      selectively altering the expression of secretable proteins. In addition, we
      observed a greater accumulation of outer-membrane vesicles from C. trachomatis in
      persistently infected cells. Taken together, these results suggest that the
      regulation of both gene expression and the secretion of chlamydial virulence
      proteins is involved in the adaptation of the bacteria to a persistent infection
      state in human genital epithelial cells.

PMID- 21737501
TI  - Oxygen reduction in the strict anaerobe Desulfovibrio vulgaris Hildenborough:
      characterization of two membrane-bound oxygen reductases.
AB  - Although Desulfovibrio vulgaris Hildenborough (DvH) is a strictly anaerobic
      bacterium, it is able to consume oxygen in different cellular compartments,
      including extensive periplasmic O2 reduction with hydrogen as electron donor. The
      genome of DvH revealed the presence of cydAB and cox genes, encoding a quinol
      oxidase bd and a cytochrome c oxidase, respectively. In the membranes of DvH, we
      detected both quinol oxygen reductase [inhibited by heptyl-hydroxyquinoline-N
      oxide (HQNO)] and cytochrome c oxidase activities. Spectral and HPLC data for the
      membrane fraction revealed the presence of o-, b- and d-type haems, in addition
      to a majority of c-type haems, but no a-type haem, in agreement with carbon
      monoxide-binding analysis. The cytochrome c oxidase is thus of the cc(o/b)o3
      type, a type not previously described. The monohaem cytochrome c553 is an
      electron donor to the cytochrome c oxidase; its encoding gene is located upstream
      of the cox operon and is 50-fold more transcribed than coxI encoding the
      cytochrome c oxidase subunit I. Even when DvH is grown under anaerobic conditions
      in lactate/sulfate medium, the two terminal oxidase-encoding genes are expressed.
      Furthermore, the quinol oxidase bd-encoding genes are more highly expressed than
      the cox genes. The cox operon exhibits an atypical genomic organization, with the
      gene coxII located downstream of coxIV. The occurrence of these membrane-bound
      oxygen reductases in other strictly anaerobic Deltaproteobacteria is discussed.

PMID- 21737502
TI  - Antitumor activity of YM155, a selective small-molecule survivin suppressant,
      alone and in combination with docetaxel in human malignant melanoma models.
AB  - PURPOSE: Aggressive cell growth and chemoresistance are notorious obstacles in
      melanoma therapy. Accumulating evidence suggests that survivin is preferentially
      expressed in cancer cells and plays a crucial role in cell division and apoptosis
      dysfunction. Here, we evaluated the therapeutic potential of YM155, a selective
      survivin suppressant, alone and in combination with docetaxel using human
      melanoma models. EXPERIMENTAL DESIGN: A375 and SK-MEL-5 human malignant melanoma
      cells were treated with siRNA, YM155, and/or docetaxel, and cell viability, mRNA
      and protein expression levels, cell-cycle distribution, and immunohistochemical
      staining were then evaluated. Furthermore, the efficacy of YM155 combined with
      docetaxel was further examined in established xenograft models. RESULTS: Survivin
      suppression was sufficient to induce spontaneous apoptosis of melanoma cells.
      YM155 showed nanomolar antiproliferative effects and induced tumor regression in
      established melanoma xenograft models. Docetaxel showed antitumor activity
      against melanoma cells, although it also induced survivin upregulation and G(2)/M
      mitotic arrest; however, cotreatment with YM155 decreased survivin expression
      below basal levels. Combination treatment of YM155 and docetaxel induced a
      greater rate of apoptosis than the sum of the single-treatment rates and promoted
      tumor regression without enhanced body weight loss in the melanoma xenograft
      models. CONCLUSIONS: Survivin is responsible for the inherent low levels of
      spontaneous apoptosis in melanoma cells. The concomitant combination of YM155
      with docetaxel diminished the accumulation of survivin in G(2)/M mitotic arrest,
      and induced more intense apoptosis compared with each single treatment. YM155 in
      combination with docetaxel is well tolerated and shows greater efficacy than
      either agent alone in mouse xenograft models.

PMID- 21737503
TI  - XPF expression correlates with clinical outcome in squamous cell carcinoma of the
      head and neck.
AB  - PURPOSE: Tumor-specific biomarkers that predict resistance to DNA damaging agents
      may improve therapeutic outcomes by guiding the selection of effective therapies
      and limiting morbidity related to ineffective approaches. XPF (ERCC4) is an
      essential component of several DNA repair pathways and XPF-deficient cells are
      exquisitely sensitive to DNA damaging agents. The purpose of this study was to
      determine whether XPF expression levels predict clinical response to DNA damaging
      agents in head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN:
      Quantitative immunohistochemistry was used to measure XPF expression in tumors
      from a cohort of 80 patients with newly diagnosed HNSCC treated with radiation
      therapy with or without platinum-based chemotherapy; samples were collected
      prospectively. Genomic DNA isolated from blood samples was analyzed for nine
      single nucleotide polymorphisms (SNP) in the XPF gene by using a custom array.
      The primary endpoint was progression-free survival (PFS). RESULTS: XPF expression
      was higher in tumors from the oral cavity than from the other sites (P < 0.01).
      High XPF expression correlated with early time to progression both by univariate
      (HR = 1.87, P = 0.03) and multivariate analysis (HR = 1.83, P = 0.05). The one
      year PFS for high expressers was 47% (95% CI = 31-62) compared with 72% (95% CI =
      55-83) for low expressers. In addition, we identified four XPF SNPs that showed
      marginal association with treatment failure. CONCLUSIONS: Expression level of XPF
      in HNSCC tumors correlates with clinical response to DNA damaging agents. XPF has
      potential to guide next generation personalized cancer therapy.

PMID- 21737504
TI  - Immunosuppression in patients with high-grade gliomas treated with radiation and
      temozolomide.
AB  - PURPOSE: Patients with high-grade gliomas (HGG) routinely receive radiation,
      temozolomide, and glucocorticoids. As each of these is immunosuppressive, we
      conducted a prospective, multicenter study to follow CD4 counts over time and
      determine whether low CD4 counts were associated with adverse outcomes.
      EXPERIMENTAL DESIGN: Patients with newly diagnosed HGG had CD4 counts drawn
      before initiating standard therapy and monthly thereafter for 1 year. Information
      on hospitalizations, infections, glucocorticoid use, survival, and cause of death
      were also collected. RESULTS: Ninety-six evaluable patients were accrued [85%
      glioblastoma, median age of 57, median Karnofsky performance status (KPS) = 90].
      The median CD4 count before radiation and temozolomide treatment was 664
      cells/mm(3). The CD4 count nadir occurred 2 months after initiating therapy when
      73% of patients had CD4 counts less than 300 cells/mm(3) and 40% had less than
      200 cells/mm(3). CD4 counts remained low throughout the year of follow-up.
      Patients with CD4 counts less than 200 cells/mm(3)at 2 months had shorter
      survival than those with higher counts (median: 13.1 vs. 19.7 months, P = 0.002).
      Median survival was related to CD4 toxicity grades (I = 23.8 months, II = 19.7
      months, III-IV = 13.1 months, P = 0.009). The adjusted HR for death attributable
      to 2-month CD4 count below 200 was 1.66 (P = 0.03). Eighty-eight percent of
      deaths resulted from disease progression, whereas only 2.5% were due to
      infection. CONCLUSIONS: Severe reductions in CD4 counts in patients with newly
      diagnosed HGG treated with radiation and temozolomide treatment are common,
      treatment-related, long-lasting, and associated with early death from tumor
      progression.

PMID- 21737505
TI  - Targeting SRC in mucinous ovarian carcinoma.
AB  - PURPOSE: Mucinous ovarian carcinomas have a distinct clinical pattern compared
      with other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific
      clinical significance of mucinous ovarian carcinomas in a large cohort and (ii)
      the functional role of Src kinase in preclinical models of mucinous ovarian
      carcinoma. EXPERIMENTAL DESIGN: A total of 1,302 ovarian cancer patients
      including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival
      analyses. Biological effects of Src kinase inhibition were tested using dasatinib
      based therapy in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2).
      RESULTS: Patients with advanced-stage mucinous ovarian cancer had significantly
      worse survival than those with serous histology: median overall survival, 1.67
      versus 3.41 years, P = 0.002; median survival time after recurrence of 0.53
      versus 1.66 years, P < 0.0001. Among multiple ovarian cancer cell lines, RMUG-S
      ip2 mucinous ovarian cancer cells showed the highest Src kinase activity.
      Moreover, oxaliplatin treatment induced phosphorylation of Src kinase. This
      induced activity by oxaliplatin therapy was inhibited by concurrent
      administration of dasatinib. Targeting Src with dasatinib in vivo showed
      significant antitumor effects in the RMUG-S-ip2 model but not in the serous
      ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with
      dasatinib further showed significant effects on reducing cell viability,
      increasing apoptosis, and in vivo antitumor effects in the RMUG-S-ip2 model.
      CONCLUSIONS: Our results suggest that poor survival of women with mucinous
      ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting
      Src kinase with a combination of dasatinib and oxaliplatin may be an attractive
      approach for this disease.

PMID- 21737506
TI  - Clonal relationship of classical hodgkin lymphoma and its recurrences.
AB  - PURPOSE: We investigated whether the first and all subsequent manifestations of
      Hodgkin lymphoma (HL) in a patient are clonally related. EXPERIMENTAL DESIGN: We
      identified a collective of 20 patients with sometimes multiple HL recurrences.
      Relapses were classified as early, that is, within twelve months (eight events in
      seven patients) or as late, that is, later than one year after the previous
      neoplasm (24 events in 17 patients). Hodgkin and Reed-Sternberg cells were
      microdissected after CD30 staining using laser capture technique. Immunoglobulin
      heavy chain (IgH) gene fragment lengths were analyzed after DNA preamplification,
      applying consensus FR3 and J primers by ABI 310 Genetic Analyzer. Sequencing of
      the amplified IgH products was carried out by ABI 3130 and 3730XL Genetic
      Analyzer. Epstein-Barr virus (EBV) association was assessed by EBV early RNA and
      LMP1. RESULTS: Three cases with early relapses after a first HL diagnosis were
      clonally related to the initial tumor, whereas three of four patients with early
      relapses after a first or second relapse were not, which was accompanied by
      change of EBV association in one case. Six patients presenting with late relapses
      were clonally unrelated, which was accompanied by change of phenotype in two
      cases and change of EBV association in one case. Two samples from recurrent
      tumors of the same patient could be successfully sequenced. These two late
      relapses were clonally unrelated by IgH fragment length and sequencing analysis.
      CONCLUSIONS: Recurrent HL, especially those accompanied by an EBV-association
      switch or after a relapse, can represent an unrelated novel neoplasm. Our finding
      might play a role in clinical decision making.

PMID- 21737508
TI  - Membranous expression of ectodomain isoforms of the epidermal growth factor
      receptor predicts outcome after chemoradiotherapy of lymph node-negative cervical
      cancer.
AB  - PURPOSE: We compared the prognostic significance of ectodomain isoforms of the
      epidermal growth factor receptor (EGFR), which lack the tyrosine kinase (TK)
      domain, with that of the full-length receptor and its autophosphorylation status
      in cervical cancers treated with conventional chemoradiotherapy. EXPERIMENTAL
      DESIGN: Expression of EGFR isoforms was assessed by immunohistochemistry in a
      prospectively collected cohort of 178 patients with squamous cell cervical
      carcinoma, and their detection was confirmed with Western blotting and reverse
      transcriptase PCR. A proximity ligation immunohistochemistry assay was used to
      assess EGFR-specific autophosphorylation. Pathways associated with the expression
      of ectodomain isoforms were studied by gene expression analysis with Illumina
      beadarrays in 110 patients and validated in an independent cohort of 41 patients.
      RESULTS: Membranous expression of ectodomain isoforms alone, without the
      coexpression of the full-length receptor, showed correlations to poor clinical
      outcome that were highly significant for lymph node-negative patients
      (locoregional control, P = 0.0002; progression-free survival, P < 0.0001; disease
      specific survival, P = 0.005 in the log-rank test) and independent of clinical
      variables. The ectodomain isoforms were primarily 60-kD products of alternative
      EGFR transcripts. Their membranous expression correlated with transcriptional
      regulation of oncogenic pathways including activation of MYC and MAX, which was
      significantly associated with poor outcome. This aggressive phenotype of
      ectodomain EGFR expressing tumors was confirmed in the independent cohort.
      Neither total nor full-length EGFR protein level, or autophosphorylation status,
      showed prognostic significance. CONCLUSION: Membranous expression of ectodomain
      EGFR isoforms, and not TK activation, predicts poor outcome after
      chemoradiotherapy for patients with lymph node-negative cervical cancer.

PMID- 21737507
TI  - Determinants of successful CD8+ T-cell adoptive immunotherapy for large
      established tumors in mice.
AB  - PURPOSE: Adoptive cell transfer (ACT) of tumor infiltrating or genetically
      engineered T cells can cause durable responses in patients with metastatic
      cancer. Multiple clinically modifiable parameters can comprise this therapy,
      including cell dose and phenotype, in vivo antigen restimulation, and common
      gamma-chain (gamma(c)) cytokine support. However, the relative contributions of
      each these individual components to the magnitude of the antitumor response have
      yet to be quantified. EXPERIMENTAL DESIGN: To systematically and quantitatively
      appraise each of these variables, we employed the Pmel-1 mouse model treating
      large, established B16 melanoma tumors. In addition to cell dose and magnitude of
      in vivo antigen restimulation, we also evaluated the relative efficacy of central
      memory (T(CM)), effector memory (T(EM)), and stem cell memory (T(SCM)) subsets on
      the strength of tumor regression as well as the dose and type of clinically
      available gamma(c) cytokines, including IL-2, IL-7, IL-15, and IL-21. RESULTS: We
      found that cell dose, T-cell differentiation status, and viral vaccine titer each
      were correlated strongly and significantly with the magnitude of tumor
      regression. Surprisingly, although the total number of IL-2 doses was correlated
      with tumor regression, no significant benefit to prolonged (>=6 doses)
      administration was observed. Moreover, the specific type and dose of gamma(c)
      cytokine only moderately correlated with response. CONCLUSION: Collectively,
      these findings elucidate some of the key determinants of successful ACT
      immunotherapy for the treatment of cancer in mice and further show that gamma(c)
      cytokines offer a similar ability to effectively drive antitumor T-cell function
      in vivo.

PMID- 21737509
TI  - The Novel HSP90 inhibitor, IPI-493, is highly effective in human
      gastrostrointestinal stromal tumor xenografts carrying heterogeneous KIT
      mutations.
AB  - PURPOSE: KIT activity is crucial for gastrointestinal stromal tumors (GIST).
      Imatinib (IMA) and sunitinib (SUN) are very effective KIT-inhibitors in patients
      with advanced GIST but have no curative potential. We evaluated the efficacy of
      the novel HSP90 inhibitor IPI-493 alone, or in combination with IMA or SUN in
      GIST xenografts with KIT mutations. EXPERIMENTAL DESIGN: Nude mice (n = 98) were
      grafted bilaterally with human GIST carrying KIT exon 11 (GIST-PSW), KIT exon 9
      (GIST-BOE), or double, KIT imatinib-sensitive exon 11 and imatinib-resistant exon
      17 mutations (GIST-48). Mice were divided into six treatment groups and dosed
      orally for 15 days as follows: (i) control group, sterile water; (ii) IMA alone;
      (iii) SUN alone; (iv) IPI-493 alone; (v) IPI-493+IMA; and (vi) IPI-493+SUN.
      RESULTS: Treatment with IPI-493 resulted in tumor growth stabilization, variable
      proliferation arrest, induction of apoptosis and necrosis, and downregulation of
      KIT and its signaling cascade, especially in the GIST-BOE model. Significant
      reduction of vessel density was observed with IPI-493 treatment, and was equal to
      SUN treatment in GIST-PSW and GIST-BOE xenografts. IPI-493 treatment effects were
      enhanced in combination with TKIs, especially with IPI-493+SUN. In our hands, IPI
      493 showed dose-dependent liver damages. CONCLUSIONS: When administered as a
      single agent in a xenograft model, the HSP90 inhibitor IPI-493 has consistent
      antitumor activity and induces KIT downregulation in GISTs with heterogeneous KIT
      mutations. IPI-493 synergizes with TKIs that are commonly used for the treatment
      of advanced or IMA-resistant GIST. The antitumor response of IPI-493 is
      particularly enhanced in combination with SUN.

PMID- 21737510
TI  - Phase II trials powered to detect tumor subtypes.
AB  - Classical phase II trial designs, including "adaptive" designs, require the
      prospective characterization of tumors. We propose a 2-stage phase II design that
      allows for characterization of tumors and selection of a tumor subtype of
      interest at the conclusion of stage 1. The stage 2 objective is either a
      classical estimate of the response rate for either the tumor or a subtype, or a
      formal test of the hypothesis that the response rate for a subtype is greater
      than the overall response rate. Considering likely scenarios, stage 1 sample
      sizes approximately range from 20 to 100 with a usual size of 50. This compares
      with typical classical stage 1 sample sizes of 12 to 30. Total sample sizes range
      from sizes identical to classical designs (tens to scores) to large sizes typical
      of phase III trials in metastatic disease (hundreds). Our design is more
      efficient than previous adaptive designs because it allows for the selection of a
      tumor subtype of interest on the basis of results from stage 1. It complements
      classical phase II and phase III designs in which investigators compare different
      treatments in similar patients and tumors by positioning a treatment as fixed
      (control) and using tumor subtype as the variable of interest.

PMID- 21737511
TI  - Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors
      that contribute to malignant progression by inducing an EMT cell phenotype.
AB  - PURPOSE: The resistance of tumors to antiangiogenic therapies is becoming
      increasingly relevant. There are currently no validated predictive biomarkers for
      selecting which cancer patients will benefit from antiangiogenic therapy. Also
      lacking are resistance biomarkers that can identify which escape pathways should
      be targeted after tumors develop resistance to VEGF treatment. Recent studies
      showed that anti-VEGF treatment can make tumor cells more aggressive and
      metastatic. However, the mechanisms and mediators of this are unidentified.
      Therefore, we aimed this study at directly identifying the tumor cell-initiated
      mechanisms responsible for the resistance of pancreatic cancer to anti-VEGF
      treatment. EXPERIMENTAL DESIGN: We established and validated two murine models of
      human pancreatic cancer resistant to the VEGF-specific antibody bevacizumab in
      vivo. We used a genome-wide analysis to directly identify which tumor-secreted
      factors were overexpressed by pancreatic cancer cells that were resistant to anti
      VEGF treatment. RESULTS: Rather than direct proangiogenic factors, we identified
      several proinflammatory factors that were expressed at higher levels in cells
      resistant to anti-VEGF treatment than in treatment-sensitive control cells. These
      proinflammatory factors acted in a paracrine manner to stimulate the recruitment
      of CD11b(+) proangiogenic myeloid cells. Also, we found that secreted factors
      overexpressed by anti-VEGF treatment-resistant pancreatic cancer cells acted in
      an autocrine manner to induce epithelial-to-mesenchymal transition (EMT) and were
      thus responsible for increased aggressiveness of bevacizumab-resistant pancreatic
      tumors. CONCLUSIONS: Our results identified proinflammatory factors and EMT
      markers as potential biomarkers for selecting patients with pancreatic cancer for
      antiangiogenic therapy.

PMID- 21737512
TI  - Review: steady and pulsed pedestals, the how and why of post-receptoral pathway
      separation.
AB  - In the mid-1990s, the Pokorny and Smith research group began a series of
      psychophysical experiments with the aim of separately measuring magnocellular
      (MC)- and parvocellular (PC)-pathway mediated achromatic contrast discrimination.
      Three paradigms provide complementary information: The pulsed-pedestal paradigm
      reveals PC contrast gain, the steady-pedestal paradigm reveals steady-state MC
      pathway sensitivity, and the pedestal-Delta-pedestal paradigm reveals MC contrast
      gain. Further studies investigated the temporal and spatial summation properties
      of the underlying mechanisms and extended the work to include measures of spatial
      resolution, chromatic contrast discrimination, the detection and identification
      of stimulus polarity, and the inferred retinal mechanisms mediating illusory
      distortions. Other laboratories have also applied the methods to the study of
      normal and clinically impaired vision. This review describes the pedestal
      methodologies, how they relate to physiology, and how they have been and should
      be employed.

PMID- 21737513
TI  - Categorical properties of the color term "GOLD".
AB  - Humans are able to categorize an infinite variety of surface colors into a small
      number of color terms. Previous studies have shown that 11 basic color terms are
      commonly used in fully developed languages. These studies usually used flat matte
      color plates as stimuli, but we can also perceive the colors of glossy surfaces
      by discounting the effect of the gloss. However, color terms such as GOLD and
      SILVER are specifically associated with glossy surfaces. In this study, we
      conducted a categorical color-naming task to examine whether the color terms GOLD
      and SILVER could be located in a stimulus space defined by combining CIE xy
      chromaticity coordinates and surface reflectance and whether they had categorical
      properties like ordinary basic color terms. We found that GOLD and SILVER were
      used for specific ranges of chromaticities with stimuli having large specular
      reflectances. Moreover, the strengths of the categorical properties, as assessed
      using measures of consistency, consensus, and reaction time, were comparable to
      those of the basic color terms, indicating that GOLD and SILVER are categorical
      color terms specifically associated with glossy surfaces. This also indicates
      that humans do not always discount surface gloss to identify colors but can
      utilize this information to categorize colors.

PMID- 21737514
TI  - Management of patients with membranous nephropathy.

PMID- 21737515
TI  - Acute renal failure with lambda light chain-derived crystals in a patient with
      IgD myeloma.
AB  - Kidney involvement with immunoglobulin crystals usually relates to a light chain
      of the kappa type, in MGUS or smoldering myeloma, frequently causing Fanconi's
      syndrome with progressive renal insufficiency. We report on a case with severe
      myeloma featuring lambda light chain-derived crystals and acute kidney injury.
      Histology showed acute tubular necrosis and tubule obstruction with crystals,
      which were also abundant inside tubule epithelial cells, macrophages and bone
      marrow plasma cells. The light chain variable domain had a normal overall primary
      structure but included 11 somatic mutations, 3 of which likely increased the
      surface hydrophobicity, as observed in previously reported kappa-type crystals.

PMID- 21737516
TI  - The chemistry of thiosulfate and vascular calcification.
AB  - BACKGROUND: Thiosulfate has been shown to inhibit vascular calcification in
      uremic rats and may inhibit calcification in humans with end-stage renal disease
      but whether this is due to a systemic or local action is unknown. The underlying
      mechanism is also unclear but complexation of calcium ions has been proposed.
      METHODS: In vitro assays were used to determine the effect of thiosulfate on
      vascular calcification and hydroxyapatite formation. RESULTS: Thiosulfate (EC50:
      1-2 mM) prevented calcification of injured or devitalized aortas but not
      uninjured aortas, and similar results were obtained with sulfate. There was no
      effect on reversal of calcification. Measurements with an ion-sensitive electrode
      (corrected for changes in ionic strength) revealed a very weak interaction
      between thiosulfate and Ca(2+) (K(a) = 10.9 +/- 1.0 * 10(-6) M(-1)) that resulted
      in a 4% decrease in ionized Ca(2+) in culture medium at 5 mM thiosulfate and a
      corresponding 5% increase in the solubility product for calcium-phosphate.
      Adjustment of the total Ca(2+) concentration to account for this did not prevent
      the inhibition of aortic calcification by thiosulfate. Thiosulfate did not
      inhibit hydroxyapatite formation from seed crystals or the calcification of
      purified elastin and did not alter medium pH. CONCLUSIONS: Thiosulfate inhibits
      vascular calcification at millimolar concentrations through a direct
      extracellular effect that does not require intact smooth muscle cells but is
      related to cellular injury. This effect is not specific for thiosulfate since
      sulfate has similar properties. Inhibition cannot be explained by effects on
      ionized calcium, calcium-phosphate solubility, pH, oxidative stress or
      hydroxyapatite formation.

PMID- 21737517
TI  - A candidate gene approach to genetic contributors to the development of IgA
      nephropathy.
AB  - BACKGROUND: Genetic factors contributing to the development of IgA nephropathy
      remain to be elucidated. METHODS: The present multicenter cross-sectional case
      control study measured genotype frequencies of 65 atherosclerotic disease-related
      gene polymorphisms in 230 Japanese patients with IgA nephropathy and 262
      apparently healthy volunteers with estimated glomerular filtration rate (eGFR)
      >=60 mL/min/1.73 m(2) and negative or trace proteinuria and hematuria by dipstick
      test [non-chronic kidney disease (CKD) participants]. Clinical characteristics at
      kidney biopsy of patients with IgA nephropathy and those at the study recruitment
      of non-CKD participants were included as covariates in multivariate logistic
      regression models. RESULTS: Among 31 gene polymorphisms with >=5% of minor
      genotype in non-CKD participants, methionine synthase MTR A2756G (D919G) was
      significantly associated with IgA nephropathy using chi(2) test even after
      controlling for family-wise error rate by the method of Bonferroni (P = 0.044). A
      multivariate nonconditional logistic regression model identified MTR A2756G as a
      significant contributor of IgA nephropathy [2756AG and GG versus AA, odds ratio
      0.42 (95% confidence interval 0.25-0.69) and 0.21 (95% confidence interval 0.06
      0.68), P(trend) < 0.001]. After each patient with IgA nephropathy was randomly
      matched to a non-CKD participant on age (+/-5 years), gender, mean arterial
      pressure (+/-5 mmHg) and eGFR (+/-5 mL/min/1.73 m(2)), a multivariate conditional
      logistic regression model also verified their significant association [odds ratio
      0.42 (95% confidence interval 0.18-1.00) and odds ratio 0.09 (95% confidence
      interval 0.01-0.73), P(trend) = 0.004]. MTR A2756G was not associated with slope
      of eGFR (mL/min/1.73 m(2)/year) in 230 patients with IgA nephropathy. CONCLUSION:
      MTR A2756G was associated with the development, but not progression, of IgA
      nephropathy.

PMID- 21737518
TI  - High chronic nephropathy detection yield in CKD subjects identified by the
      combination of albuminuria and estimated GFR.
AB  - BACKGROUND AND OBJECTIVES: Epidemiological studies have shown that the burden of
      chronic kidney disease (CKD) is huge. CKD is a non-specific diagnosis, however,
      and it is hard to say which renal disorders comprise the body of CKD diagnosed on
      the strength of the combination of albuminuria and estimated glomerular
      filtration rate (eGFR) in epidemiological studies, or just how efficient such
      studies are in detecting chronic nephropathies. METHODS: The INCIPE study
      identified 524 CKD cases (using the K/DOQI definition based on albuminuria and
      eGFR) in a random sample of 4000 Italians >40 years old, 262 of whom were
      randomly chosen to be investigated in order to confirm their CKD and complete a
      diagnostic workup. We a priori defined diagnostic algorithms for 14 renal
      conditions based on personal family history, medical records, urine tests, kidney
      ultrasound with colour-Doppler and other tests. RESULTS: Among the subjects whose
      CKD was confirmed, a diagnosis of chronic nephropathy was reached in 68% of cases
      recognized as having either a specific (38%) or an undetermined (30%) kidney
      disease. Almost 50% of subjects with a specific chronic nephropathy had a
      diabetic or vascular renal disease. Abnormalities consistent with a chronic
      nephropathy were found in 50, 68, 70 and 100% of subjects with CKD Stages 1, 2, 3
      and 4, respectively. Lone low eGFR and lone microalbuminuria were observed in 20
      and 12%, respectively. CONCLUSION: In Caucasians >40 years old with a confirmed
      CKD condition, (i) an impressive 68% of subjects have an underlying chronic
      nephropathy, so eGFR and albuminuria are very efficient in detecting renal
      diseases; (ii) in 32%, the only disclosed renal abnormalities were a glomerular
      filtration rate <60 mL/min/1.73 m(2) or microalbuminuria; follow-up studies are
      needed to clarify whether these abnormalities do really identify a chronic
      nephropathy or just a cardiovascular risk condition.

PMID- 21737519
TI  - Identification of functional CCAAT/enhancer-binding protein and Ets protein
      binding sites in the human chorionic somatomammotropin enhancer sequences.
AB  - The human chorionic somatomammotropin (CS) A and B genes (listed as CSH1 and CSH2
      in the HUGO database) are highly expressed in placenta. A 241 bp potent enhancer,
      nucleotides (nts) 1-241, located at the 3' end of the CS-B gene (CS-Benh)
      stimulates promoter activity specifically in placental trophoblast cells in
      vitro. Strong activity is exerted by a 23 bp element within the CS-Benh (nts 117
      139), shown to interact with transcription enhancer factor (TEF) members of the
      transcription enhancer activator (TEA) DNA-binding domain-containing family. An
      identical TEF element is present in the homologous (97.5%) CS-Aenh; however, a
      few nucleotide differences suppress its activity. Previously, we identified
      regulatory sequences distinct from the TEF element within an 80 bp modulatory
      domain (nts 1-80) in the CS-Benh. Using structural and functional assays we now
      show that CCAAT/enhancer-binding protein (C/EBP) binding sites exist in the 80 bp
      modulatory domains of both enhancers, and an Elk-1 binding site exists in the
      modulatory domain of the CS-Aenh. C/EBPalpha or C/EBPbeta strongly repressed
      CSp.CAT activity but stimulated CSp.CAT.CS-Benh activity. In contrast, the
      equivalent CS-A enhancer sequences were unable to relieve promoter repression.
      Elk-1 overexpression also resulted in differential effects on the CS-Aenh versus
      CS-Benh. Finally, we provide evidence for the association of C/EBPbeta with the
      CS-A and CS-B genes in human placental chromatin, including differential
      involvement of C/EBPbeta with the CS-Aenh versus the CS-Benh, and therefore
      consistent with the notion that these are regions of regulatory significance in
      vivo. We conclude that members of the C/EBP and Ets families can differentially
      modulate CS-Benh and CS-Aenh activity.

PMID- 21737520
TI  - More than meets the eye: clinical reflection and evidence-based practice in an
      unusual case of adolescent chronic ankle sprain.
AB  - BACKGROUND AND PURPOSE: Adolescents who have chronic pain after common orthopedic
      injuries such as ankle sprains may present a multidimensional clinical problem
      stemming from both physical and psychological issues. A traumatic incident such
      as a motor vehicle accident can produce clinical issues ranging from a specific
      tissue injury to multisystem complications such as complex regional pain syndrome
      (CRPS) or posttraumatic stress disorder (PTSD). The purpose of this retrospective
      case report on an adolescent with chronic ankle pain stemming from a motor
      vehicle accident is to demonstrate how reflection and the evidence base
      influenced the modification of the plan of care. Description of the screening
      methods, clinical findings, interventions, and outcomes of the case may help
      physical therapists identify and improve the quality of care in cases of
      suspected CRPS and PTSD. CASE DESCRIPTION: The patient was a 12-year-old girl
      with a medical diagnosis of recurrent right ankle sprain and with signs of
      potential CRPS and PTSD. Poor initial response to ankle sprain management led to
      reflective reconsideration of the diagnosis and plan of care. The revised plan of
      care supported by the evidence base emphasized empathetic consideration of the
      traumatic motor vehicle accident and focused on CRPS prevention and management of
      potential non-physical pain via mirror therapy and motor imagery therapy.
      OUTCOMES: Pain was relieved, behavior improved, and functional movement began to
      normalize after 3 sessions of mirror therapy and motor imagery therapy.
      DISCUSSION: Patient symptoms were inconsistent with the medical diagnosis, and
      the clinical outcome of the original plan of care was unsuccessful. Reflection
      inspired a more-detailed history and systems review, which led to greater
      understanding and more-effective care.

PMID- 21737521
TI  - Effects of high-intensity inspiratory muscle training following a near-fatal
      gunshot wound.
AB  - BACKGROUND AND PURPOSE: Severe injuries sustained during combat may classify
      individuals as undeployable for active service. It is imperative that every
      effort is made to optimize physical function following such injuries. CASE
      DESCRIPTION: A 38-year-old man sustained a gunshot wound during armed combat. The
      bullet entered via the left axilla and exited from the right side of the abdomen,
      resulting in severe thoracic and abdominal injuries. Five months later, he
      continued to describe severe dyspnea on exertion. During a cardiopulmonary
      exercise test on a cycle ergometer, he achieved a maximum rate of oxygen uptake
      of 2,898 mL.min(-1) (114% predicted) and maximum power of 230 W (114% predicted).
      His maximum forced inspiratory flow was 5.95 L.s(-1), and inspiratory reserve
      volume at test end was ~80 mL. The test was terminated by the patient due to
      dyspnea that was too severe to tolerate. Video fluoroscopy demonstrated impaired
      right hemidiaphragm function. The main goals of therapy were to reduce dyspnea on
      exertion and to enable return to full work duties. A program of high-intensity,
      interval-based threshold inspiratory muscle training (IMT) was undertaken.
      OUTCOMES: An average of 5 sessions of IMT were completed each week for 10 weeks.
      During a repeat cardiopulmonary exercise test, the patient achieved a similar
      power and maximum rate of oxygen uptake. His maximum forced inspiratory flow
      increased by 48% to 8.83 L.s(-1), and he was limited by leg fatigue. DISCUSSION:
      High-intensity IMT was safe and well tolerated. It was associated with
      improvements in maximum forced inspiratory flow and changed the locus of symptom
      limitation during high-intensity exercise from dyspnea to leg fatigue.

PMID- 21737522
TI  - Physical therapist management of stiff person syndrome in a 24-year-old woman.
AB  - BACKGROUND AND PURPOSE: Stiff person syndrome is a rare neurological disorder
      characterized by stiffness and painful spasms primarily in the trunk and lower
      extremities. The role of physical therapy in the management of this disorder is
      disputed and the efficacy of specific interventions is unknown. CASE DESCRIPTION:
      The patient was a 24-year-old woman with a 1-year history of stiff person
      syndrome who received outpatient physical therapy over the course of 15 weeks.
      She had pain, muscle spasms, gait anomalies, and range-of-motion deficits, which
      affected her left lower extremity. Physical therapy interventions consisted of
      ultrasound, soft tissue mobilizations, manual stretching, and exercise. She also
      was fitted for a custom-made ankle-foot orthosis. Outcome This patient showed
      decreased pain and muscle spasms, as well as improvements in gait and range of
      motion. DISCUSSION: Stiffness and spasms interfere with the ability of these
      patients to fully mobilize affected joints, and they are at risk of developing
      further complications. Physical therapy may have a role in the management of this
      disease, as these patients need to be taught how to properly stretch and maintain
      joint mobility as a lifelong commitment.

PMID- 21737523
TI  - Treatment for a 14-year-old girl with Lyme disease using therapeutic exercise and
      gait training.
AB  - BACKGROUND AND PURPOSE: Lyme disease is well documented in the literature;
      however, specific physical therapy interventions for the pediatric population
      with residual effects of Lyme disease have not been addressed. The purposes of
      this retrospective case report are: (1) to present an example of a therapeutic
      intervention for a pediatric patient in the late stages of Lyme disease with
      related musculoskeletal dysfunction and severely impaired quality of life, (2) to
      report the patient's functional outcomes from treatment, and (3) to discuss
      implications for treatment of patients with musculoskeletal dysfunction in the
      late stages of Lyme disease. CASE DESCRIPTION: The patient was a 14-year old girl
      who had contracted Lyme disease 1 year prior to initiation of physical therapy.
      She was unable to participate with her peers in school, church, and sporting
      events due to significant impairments in strength (force-generating capacity),
      endurance, and gait; fatigue; pain; and total body tremor. Therapeutic exercise
      and gait training were used for treatment. The patient actively participated in
      managing her care by providing feedback during interventions and setting goals.
      OUTCOMES: After 18 weeks of treatment, the patient achieved 96.7% of her
      predicted distance on the Six-Minute Walk Test with normal gait mechanics and
      returned to playing high school sports. She had a manual muscle test grade of 4/5
      or greater in major extremity muscle groups. She returned to school and church
      participation with minimal total body tremor when fatigued and daily pain rated 0
      to 3/10. DISCUSSION: Therapeutic exercise and gait training may facilitate return
      to function in an adolescent patient with late effects of Lyme disease. Further
      investigation is advised to establish treatment effects in a broader population.

PMID- 21737524
TI  - Health services research in Europe: evaluating and improving its contribution to
      health care policy.

PMID- 21737525
TI  - Health technology assessment: research trends and future priorities in Europe.
AB  - OBJECTIVE: To provide an overview of health services research related to health
      technology assessment (HTA) and to identify research priorities from a European
      perspective. METHODS: Several methods were used: systematic review of articles
      indexed with the MeSH term 'technology assessment' in PubMed from February 1999
      2009; online survey among experts; and conference workshop discussions. RESULTS:
      Research activity in HTA varies considerably across Europe. The research was
      categorised into six areas: (1) the breadth of analysis in HTA (such as economic,
      organizational and social aspects); (2) HTA products developed to meet the needs
      of policy-makers (such as horizon scanning, mini-HTA, and core HTA); (3) handling
      life-cycle perspectives in relation to technologies; (4) topics that challenge
      existing methods and for which HTA should be developed to address the themes more
      comprehensively (such as public health interventions and organizational
      interventions); (5) development of HTA capacity and programmes; and (6) links
      between policy and HTA. An online survey showed that the three areas that were
      given priority were the relationship between HTA and policy-making (71%), the
      impact of HTA (62%) and incorporating patient aspects in HTA (50%). Policy-makers
      highlighted HTA and innovation processes as their main research priority (42%).
      Areas that the systematic review identified as future priorities include issues
      within the six existing research areas such as disinvestment, developing evidence
      for new technologies, assessing the wider effects of technology use, and
      determining how HTA affects decision-making. In addition, relative effectiveness
      and individualized treatments are areas of growing interest. CONCLUSIONS: The
      research priorities identified are important for obtaining high quality and cost
      effective health care in Europe. Managing the introduction, use and phasing out
      of technologies challenges health services throughout Europe, and these processes
      need to be improved to successfully manage future more general challenges. An
      ageing population and a diminishing workforce both require strong efforts to
      ensure effective and well-organized use of human resources and technologies.
      Furthermore, Europe needs to focus on innovation. This is closely linked to use
      of technologies and calls for future research.

PMID- 21737526
TI  - European priorities for research on health care organizations and service
      delivery.
AB  - OBJECTIVES: To provide an overview of the principal areas of research on health
      care organization and service delivery and to identify priority areas from a
      European comparative perspective. Given the large quantity of articles produced
      on health care organizations, we focus on primary care and hospital care. METHOD:
      A combination of methods was used for describing past and current research: (i)
      bibliometric analyses of published research in Pubmed and Embase 2000-09; (ii) a
      further classification of research based on a sample of 1,010 articles; and (iii)
      an identification of relevant EU-funded projects over the period 2000-10. An
      online survey of experts was carried out to identify priorities. The results were
      refined through conference discussions. RESULTS: Research into health care
      organizations varies considerably across Europe. This is only partly associated
      with differences in countries' gross domestic product or population. Studies were
      categorized into four main domains: intra-organizational control; inter
      organizational relations; patient relations; and governance and accountability.
      Past and current research may not reflect future priorities as the domain of
      'inter-organizational relations' is regarded by most experts as the top priority
      for the future, while the smallest share in the sample of published research and
      EU-funded projects fell into that category. Expert views show considerable
      homogeneity, regardless of their role in the health care system or their country.
      Specific future priorities include the integration of care across organizational
      boundaries (including the relationship between primary and secondary care),
      patient involvement and participation and workforce skill-mix. CONCLUSIONS: The
      research priorities identified in this study relate to important shared
      challenges in Europe's health care systems. This makes cross-border learning
      important, especially given the clear geographical variation in health services
      research (HSR) funding and capacity in Europe.

PMID- 21737527
TI  - Mapping research on health systems in Europe: a bibliometric assessment.
AB  - OBJECTIVE: Europe's health care decision-makers are facing an increasingly
      complex and rapidly changing landscape. It is crucial that health care problems
      are addressed with evidence-informed policy and that evidence finding is aimed at
      those topics most urgent on policy agendas. Research on health systems addresses
      the macro-level of health care delivery and aims at generating evidence for
      policy-making. Our aim was to assess the field of health systems research in
      Europe, primarily based on an analysis of the published literature. METHODS:
      Starting from current definitions of health systems, during 2004-09 we identified
      four thematic areas for research and defined keywords to construct a sensitive
      literature search limited to European research. RESULTS: The database search
      resulted in 26,945 hits between 2004-09. Until 2008, the annual number of
      publications on health systems research increased at an average rate of 5.2%.
      Most (88%) were in English. The largest producer of research on health systems
      has been the UK (nearly 10,000 in six years; 37% of the total for Europe), which
      is also the country most frequently the object of research. In contrast, seven
      countries had produced no publications. There were modest correlations between a
      country's research production and its gross domestic product (r = 0.62) but less
      so with its population size (0.33). The most frequent keywords were 'patients'
      (49% of all references), 'patient satisfaction' (27%), 'organization and
      administration' (23%), 'education' (19%) and 'attitude of health personnel'
      (13%). Closer inspection of a sub-sample of 1000 abstracts revealed that only 24%
      met our definition of 'health systems research' rather than other fields of
      health services research. CONCLUSION: There is a wide-spread need to develop
      health systems research capacity, in particular in eastern European countries,
      and to address the effects of health care reform, particularly the effects of
      privatization and commercialization of health services.

PMID- 21737528
TI  - Health services research related to performance indicators and benchmarking in
      Europe.
AB  - OBJECTIVE: Measuring quality of care through performance indicators and
      subsequently using these to compare, learn, and improve (benchmarking) has become
      a central component of health care policy. This paper aims to identify the main
      themes of health services research in this area and focuses on opportunities for
      improving the evidence underpinning performance indicators. METHODS: A literature
      survey was carried out to identify research activities and main research themes
      in Europe in the years 2000-09. Identified literature was categorized into sub
      topics and for each topic the main methodological issues were identified and
      discussed. Experts validated the findings and explored the potential for related
      further European research. RESULTS: The distribution of research on performance
      and benchmarking across EU member states varies in time, scope and settings with
      a large amount of studies focusing on hospitals. Eight specific fields of
      research were identified (research on concepts and performance frameworks;
      performance indicators and benchmarking using mortality data; performance
      indicators and benchmarking related to cancer care; performance indicators and
      benchmarking on care delivered in hospitals; patient safety indicators;
      performance indicators in primary care; patient experience; research on the
      practice of benchmarking and performance improvement). Expert discussions
      confirmed that research on performance indicators and benchmarking should focus
      on the development of indicators, as well as their use. The research should
      involve the potential users and incorporate scientific approaches from
      biomedicine and epidemiology as well as the social sciences. Further progress is
      hampered by data availability. Issues which need to be addressed include the use
      of unique patient identifiers (UPIs) to facilitate linkages between separate
      databases; standardized measurement of the experiences of patients and others;
      and deepening collaboration between Eurostat, the World Health Organization
      (WHO), and the Organization for Economic Co-operation and Development (OECD) to
      facilitate the availability of internationally comparable performance
      information. CONCLUSIONS: This study suggests a number of themes for future
      research. These include testing and improving: the validity and reliability of
      performance indicators, especially related to avoidable mortality and other
      outcome indicators; the effectiveness and efficiency of embedding performance
      indicators in the various governance, monitoring and management models, and their
      effect on health systems, services and professionals; and the effectiveness and
      efficiency of linking performance indicators to other national and international
      strategies and policies such as accreditation and certification, practice
      guidelines, audits, quality systems, patient safety strategies, national
      standards on volume and/or quality, public reporting, pay-for-performance and
      patient/consumer involvement. The field would benefit from strengthening the
      clearinghouse function for research findings, training of researchers and
      appropriate scientific publication media. Results should be systematically shared
      with policy-makers and managers, and networking stimulated between the growing
      number of regional and national institutes involved in quality measurement and
      reporting.

PMID- 21737529
TI  - Health services research in Europe and its use for informing policy.
AB  - OBJECTIVE: As an applied field of research, health services research (HSR) is
      undertaken primarily to inform health care policy. However, the relationship
      between policy and HSR is not straightforward. Many policies are developed
      without taking account of available evidence. Our objective was to provide an
      overview of the infrastructure and capacity of HSR in Europe, and to explore the
      links between HSR and policy in European countries. METHODS: A survey of health
      policy experts in 34 European countries undertaken between September 2009 and
      June 2010, covering: funding and prioritizing HSR; production and producers of
      HSR; health policy users of HSR; activities to promote the use of HSR; and
      barriers and facilitators to using HSR in policy-making. Experts were selected
      based on their professional expertise and reputation in HSR and/or health policy.
      RESULTS: Information was returned from 30 of the 34 countries. Infrastructure and
      capacity for HSR varied widely across countries as did the mechanisms likely to
      promote the use of research for national policy-making. In many cases, HSR was
      not separately identified from other health-related research. Government funding
      for HSR varied between zero and over ?170 million per year (in 2004). Few
      countries had mechanisms to match HSR priorities with those of policy-makers.
      Although most countries provided some relevant training, multidisciplinary
      training was available in few countries. Few mechanisms supporting the use of
      research in policy were reported. One exception was coverage decisions for new
      drugs and technologies where formal accountability for the use of health
      technology assessments appeared to be most developed. Overall, respondents
      struggled to locate information on many aspects of HSR, particularly its use in
      decision-making. CONCLUSION: HSR is unevenly developed across Europe. There is
      considerable scope to build the infrastructure and to take steps to improve the
      use of HSR in policy-making. There is also a need for research, as opposed to
      expert opinion, on how HSR is undertaken and used.

PMID- 21737530
TI  - Prodrugs--from serendipity to rational design.
AB  - The prodrug concept has been used to improve undesirable properties of drugs
      since the late 19th century, although it was only at the end of the 1950s that
      the actual term prodrug was introduced for the first time. Prodrugs are inactive,
      bioreversible derivatives of active drug molecules that must undergo an enzymatic
      and/or chemical transformation in vivo to release the active parent drug, which
      can then elicit its desired pharmacological effect in the body. In most cases,
      prodrugs are simple chemical derivatives that are only one or two chemical or
      enzymatic steps away from the active parent drug. However, some prodrugs lack an
      obvious carrier or promoiety but instead result from a molecular modification of
      the prodrug itself, which generates a new active compound. Numerous prodrugs
      designed to overcome formulation, delivery, and toxicity barriers to drug
      utilization have reached the market. In fact, approximately 20% of all small
      molecular drugs approved during the period 2000 to 2008 were prodrugs. Although
      the development of a prodrug can be very challenging, the prodrug approach
      represents a feasible way to improve the erratic properties of investigational
      drugs or drugs already on the market. This review introduces in depth the
      rationale behind the use of the prodrug approach from past to present, and also
      considers the possible problems that can arise from inadequate activation of
      prodrugs.

PMID- 21737532
TI  - Regulators of G-protein signaling and their Galpha substrates: promises and
      challenges in their use as drug discovery targets.
AB  - Because G-protein coupled receptors (GPCRs) continue to represent excellent
      targets for the discovery and development of small-molecule therapeutics, it is
      posited that additional protein components of the signal transduction pathways
      emanating from activated GPCRs themselves are attractive as drug discovery
      targets. This review considers the drug discovery potential of two such
      components: members of the "regulators of G-protein signaling" (RGS protein)
      superfamily, as well as their substrates, the heterotrimeric G-protein alpha
      subunits. Highlighted are recent advances, stemming from mouse knockout studies
      and the use of "RGS-insensitivity" and fast-hydrolysis mutations to Galpha, in
      our understanding of how RGS proteins selectively act in (patho)physiologic
      conditions controlled by GPCR signaling and how they act on the nucleotide
      cycling of heterotrimeric G-proteins in shaping the kinetics and sensitivity of
      GPCR signaling. Progress is documented regarding recent activities along the path
      to devising screening assays and chemical probes for the RGS protein target, not
      only in pursuits of inhibitors of RGS domain-mediated acceleration of Galpha GTP
      hydrolysis but also to embrace the potential of finding allosteric activators of
      this RGS protein action. The review concludes in considering the Galpha subunit
      itself as a drug target, as brought to focus by recent reports of activating
      mutations to GNAQ and GNA11 in ocular (uveal) melanoma. We consider the
      likelihood of several strategies for antagonizing the function of these oncogene
      alleles and their gene products, including the use of RGS proteins with Galpha(q)
      selectivity.

PMID- 21737533
TI  - Orphans in the human cytochrome P450 superfamily: approaches to discovering
      functions and relevance in pharmacology.
AB  - As a result of technical advances in recombinant DNA technology and nucleotide
      sequencing, entire genome sequences have become available in the past decade and
      offer potential in understanding diseases. However, a central problem in the
      biochemical sciences is that the functions of only a fraction of the
      genes/proteins are known, and this is also an issue in pharmacology. This review
      is focused on issues related to the functions of cytochrome P450 (P450) enzymes.
      P450 functions can be categorized in several groups: 1) Some P450s have critical
      roles in the metabolism of endogenous substrates (e.g., sterols and fat-soluble
      vitamins). 2) Some P450s are not generally critical to normal physiology but
      function in relatively nonselective protection from the many xenobiotic chemicals
      to which mammals (including humans) are exposed in their diets [as well as more
      anthropomorphic chemicals (e.g., drugs, pesticides)]. 3) Some P450s have not been
      extensively studied and are termed "orphans" here. With regard to elucidation of
      any physiological functions of the orphan P450s, the major subject of this
      review, it is clear that simple trial-and-error approaches with individual
      substrate candidates will not be very productive in addressing questions about
      function. A series of liquid chromatography/mass spectrometry/informatics
      approaches are discussed, along with some successes with both human and bacterial
      P450s. Current information on what are still considered "orphan" P450s is
      presented. The potential for application of some of these approaches to other
      enzyme systems is also discussed.

PMID- 21737531
TI  - Activation and regulation of purinergic P2X receptor channels.
AB  - Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven
      possible subunits, denoted P2X1 to P2X7. Each subunit contains a large
      ectodomain, two transmembrane domains, and intracellular N and C termini.
      Functional P2XRs are organized as homomeric and heteromeric trimers. This review
      focuses on the binding sites involved in the activation (orthosteric) and
      regulation (allosteric) of P2XRs. The ectodomains contain three ATP binding
      sites, presumably located between neighboring subunits and formed by highly
      conserved residues. The detection and coordination of three ATP phosphate
      residues by positively charged amino acids are likely to play a dominant role in
      determining agonist potency, whereas an AsnPheArg motif may contribute to binding
      by coordinating the adenine ring. Nonconserved ectodomain histidines provide the
      binding sites for trace metals, divalent cations, and protons. The transmembrane
      domains account not only for the formation of the channel pore but also for the
      binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N
      and C- domains provide the structures that determine the kinetics of receptor
      desensitization and/or pore dilation and are critical for the regulation of
      receptor functions by intracellular messengers, kinases, reactive oxygen species
      and mercury. The recent publication of the crystal structure of the zebrafish
      P2X4.1R in a closed state provides a major advance in the understanding of this
      family of receptor channels. We will discuss data obtained from numerous site
      directed mutagenesis experiments accumulated during the last 15 years with
      reference to the crystal structure, allowing a structural interpretation of the
      molecular basis of orthosteric and allosteric ligand actions.

PMID- 21737535
TI  - Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up
      regulating natriuretic peptide receptor-A expression in the renal inner medullary
      collecting duct in decompensated heart failure.
AB  - In heart failure, the renal responsiveness to exogenous and endogenous atrial
      natriuretic peptide (ANP) is blunted. The mechanisms of renal hyporesponsiveness
      to ANP are complex, but one potential mechanism is decreased expression of
      natriuretic peptide receptor-A (NPR-A) in inner medullary collecting duct (IMCD)
      cells. Newly emerging evidence shows that glucocorticoids could produce potent
      diuresis and natriuresis in patients with heart failure, but the precise
      mechanism is unclear. In the present study, we found dexamethasone (Dex)
      dramatically increased the expression of NPR-A in IMCD cells in vitro. The NPR-A
      overexpression induced by Dex presented in a time- and dose-dependent manner,
      which emerged after 12 h and peaked after 48 h. The cultured IMCD cells were then
      stimulated with exogenous rat ANP. Consistent with the findings with NPR-A
      expression, Dex greatly increased cGMP (the second messenger for the ANP)
      generation in IMCD cells, which presented in a time- and dose-dependent manner as
      well. In rats with decompensated heart failure, Dex dramatically increased NPR-A
      expression in inner renal medulla, which was accompanied by a remarkable increase
      in renal cGMP generation, urine flow rate, and renal sodium excretion. It is
      noteworthy that Dex dramatically lowered plasma ANP, cGMP levels, and left
      ventricular end diastolic pressure. These favorable effects induced by Dex were
      glucocorticoid receptor (GR)-mediated and abolished by the GR antagonist 17beta
      hydroxy-11beta-[4-dimethylamino phenyl]-17alpha-[1-propynyl]estra-4,9-dien-3-one
      (RU486). Collectively, glucocorticoids could improve renal responsiveness to ANP
      by up-regulating NPR-A expression in the IMCD and induce a potent diuretic action
      in rats with decompensated heart failure.

PMID- 21737536
TI  - Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists
      differentially regulate 5-HT2A receptor protein level in vivo.
AB  - Dysregulation of the 5-HT(2A) receptor is implicated in both the etiology and
      treatment of schizophrenia. Although the essential role of 5-HT(2A) receptors in
      atypical antipsychotic drug actions is widely accepted, the contribution of 5
      HT(2A) down-regulation to their efficacy is not known. We hypothesized that down
      regulation of cortical 5-HT(2A) receptors contributes to the therapeutic action
      of atypical antipsychotic drugs. To test this hypothesis, we assessed the effect
      of chronically administered antipsychotics (clozapine, olanzapine, and
      haloperidol) and several 5-HT(2A) antagonists [ketanserin, altanserin, alpha-(2,3
      dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (M100907),
      alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethano (M11939), 4-[(2Z)-3-{[2
      (dimethylamino)ethoxy]amino}-3-(2-fluorophenyl)prop-2-en-1-ylidene]cyclohexa-2,5
      dien-1-one (SR46349B), and pimavanserin], on the phencyclidine (PCP)-induced
      hyperlocomotor response and cortical 5-HT(2A) receptor levels in C57BL/6J mice.
      Clozapine and olanzapine, but not haloperidol, induced receptor down-regulation
      and attenuated PCP-induced locomotor responses. Of the selective 5-HT(2A)
      antagonists tested, only ketanserin caused significant receptor protein down
      regulation, whereas SR46349B up-regulated 5-HT(2A) receptors and potentiated PCP
      hyperlocomotion; the other 5-HT(2A) receptor antagonists were without effect. The
      significance of these findings with respect to atypical antipsychotic drug action
      is discussed.

PMID- 21737537
TI  - Glycyrrhizin prevents liver injury by inhibition of high-mobility group box 1
      production by Kupffer cells after ischemia-reperfusion in rats.
AB  - High-mobility group box 1 (HMGB1) acts as an early mediator of inflammation and
      organ damage in hepatic ischemia-reperfusion (I/R) injury. Glycyrrhizin is a
      natural anti-inflammatory and antiviral triterpene in clinical use. The purpose
      of this study was to investigate the effect of glycyrrhizin on liver injury
      caused by I/R and production of HMGB1 by Kupffer cells in rats. In the first test
      period, rats were given saline or glycyrrhizin 20 min before segmental hepatic
      warm I/R. Serum alanine aminotransferase and HMGB1 levels and hepatic
      histopathological findings were evaluated after I/R. Furthermore, expression of
      HMGB1 in the liver was assessed by immunohistochemical staining after I/R.
      Kupffer cells were isolated by collagenase digestion and differential
      centrifugation, and production of HMGB1 was assessed. In another set of
      experiments, the effect of inhibition of Kupffer cells by injection of liposome
      entrapped dichloromethylene diphosphonate (lipo-MDP) on liver injury and
      expression of HMGB1 were investigated after I/R. Liver injury was prevented in
      the glycyrrhizin group compared with the control group. Furthermore, serum HMGB1
      levels were also significantly blunted in the glycyrrhizin group compared with
      the control group. Cells expressing HMGB1 were detected in the hepatic sinusoid
      by immunohistochemistry and recognized morphologically as Kupffer cells.
      Furthermore, the expression of HMGB1 was reduced in the glycyrrhizin group
      compared with the control group. Production of HMGB1 was reduced in Kupffer cells
      isolated from the glycyrrhizin group compared with the control group. It is
      noteworthy that treatment with lipo-MDP significantly blunted serum HMGB1 levels
      and prevented liver injury after I/R. These results suggest that glycyrrhizin has
      the therapeutic potential to prevent warm I/R-induced injury during hepato
      biliary surgery.

PMID- 21737534
TI  - Endoplasmic reticulum Ca(2+) handling in excitable cells in health and disease.
AB  - The endoplasmic reticulum (ER) is a morphologically and functionally diverse
      organelle capable of integrating multiple extracellular and internal signals and
      generating adaptive cellular responses. It plays fundamental roles in protein
      synthesis and folding and in cellular responses to metabolic and proteotoxic
      stress. In addition, the ER stores and releases Ca(2+) in sophisticated scenarios
      that regulate a range of processes in excitable cells throughout the body,
      including muscle contraction and relaxation, endocrine regulation of metabolism,
      learning and memory, and cell death. One or more Ca(2+) ATPases and two types of
      ER membrane Ca(2+) channels (inositol trisphosphate and ryanodine receptors) are
      the major proteins involved in ER Ca(2+) uptake and release, respectively. There
      are also direct and indirect interactions of ER Ca(2+) stores with plasma
      membrane and mitochondrial Ca(2+)-regulating systems. Pharmacological agents that
      selectively modify ER Ca(2+) release or uptake have enabled studies that revealed
      many different physiological roles for ER Ca(2+) signaling. Several inherited
      diseases are caused by mutations in ER Ca(2+)-regulating proteins, and perturbed
      ER Ca(2+) homeostasis is implicated in a range of acquired disorders. Preclinical
      investigations suggest a therapeutic potential for use of agents that target ER
      Ca(2+) handling systems of excitable cells in disorders ranging from cardiac
      arrhythmias and skeletal muscle myopathies to Alzheimer disease.

PMID- 21737538
TI  - Simultaneous bilateral posterior thoracotomy with the patient in the prone
      position for resection of bilateral posterior lung metastases.
AB  - Lung metastases limited to posterior segments can be removed through a posterior
      thoracotomy with the patient in the prone position. When these metastases are
      bilateral, a simultaneous approach can be performed. We present three cases of
      bilateral lung metastases of colorectal carcinoma removed through a simultaneous
      bilateral posterior thoracotomy with the patient in the prone position.

PMID- 21737539
TI  - Combined valve-sparing root replacement and total arch replacement with frozen
      elephant trunk.
AB  - We report a case of simultaneous repair of an extensive thoracic aortic aneurysm
      from the aortic root to the distal aortic arch. A 54-year-old male had
      annuloaortic ectasia and a transverse aortic and distal arch aneurysm. Aneurysms
      of the descending aorta and the abdominal aorta were also demonstrated. The
      patient underwent aortic valve-sparing root reconstruction, replacement of the
      aortic arch and placement of a frozen elephant trunk stent-graft concomitantly
      through a median sternotomy incision. Because a complicated procedure was
      necessary, root reconstruction was performed first and coronary perfusion was
      resumed. This case suggests that the surgical procedure should be determined on
      the bases of the situation of thoracic aortic aneurysm and the general condition
      of the patient. Treatment for extensive diseased aorta from the aortic root to
      the distal aortic arch is a surgical challenge. Although single-stage repair is
      one of the options for this condition, it is very invasive. Total arch
      replacement with the frozen elephant trunk technique is efficacious to exclude
      distal arch aneurysm or descending aortic aneurysm through median sternotomy. An
      aortic valve-sparing operation was developed to preserve the native aortic valve
      function in order to improve the patient's quality of life. We herein report a
      case of concomitant total arch replacement using a frozen elephant trunk and
      aortic valve-sparing operation for extensive thoracic aortic aneurysm.

PMID- 21737540
TI  - Are there any good treatments for keloid scarring after sternotomy?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: in patients with hypertrophic and keloid
      scarring of the sternotomy wound, is surgical excision with or without adjuvant
      treatment of any benefit in reducing the size of the scar? Altogether, more than
      15 papers were found using the reported search, of which nine represented the
      best evidence to answer the clinical question. The authors, journal, date and
      country of publication, patient group studied, study type, relevant outcomes and
      results of these papers are tabulated. One of the studies showed no difference
      between surgery and adjunctive triamcinolone or colchicine. One study showed that
      incomplete excision resulted in higher recurrence rates. Postoperative radiation
      was found to be useful in two of the studies, although one study showed that it
      was not useful. One randomized control trial showed improvement after laser
      compared to no treatment. Two other trials showed no difference between laser,
      silicone gel, intralesional steroid or 5-fluorouracil. One trial showed that
      perioperative systemic steroid application gave rise to no improvement but in
      fact worsened scar formation. We conclude that small keloids can be treated
      radically by surgery with adjuvant therapy (radiation or corticosteroid
      injections) or by non-surgical therapy (corticosteroid injections, laser and anti
      tumour/immunosuppressive agents, such as 5-fluorouracil). Large and multiple
      keloids are difficult to treat radically and are currently only treatable by
      multimodal therapies that aim to relieve symptoms.

PMID- 21737541
TI  - Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract
      infection.
AB  - We describe the success of adjunctive bacteriophage therapy for refractory
      Pseudomonas aeruginosa urinary tract infection in the context of bilateral
      ureteric stents and bladder ulceration, after repeated failure of antibiotics
      alone. No bacteriophage-resistant bacteria arose, and the kinetics of
      bacteriophage and bacteria in urine suggest self-sustaining and self-limiting
      infection.

PMID- 21737542
TI  - Antimicrobial resistance and distribution of sul genes and integron-associated
      intI genes among uropathogenic Escherichia coli in Queensland, Australia.
AB  - We studied 137 uropathogenic Escherichia coli (UPEC) isolates from hospitalized
      adult patients (Queensland, Australia) for their resistance to 17 antimicrobial
      agents using the calibrated dichotomous sensitivity method and the presence of
      class I, II and III integron-associated integrase (intI) genes, including
      functional class II intI2, as well as the presence of sul1, sul2 and sul3 genes,
      using PCR. Randomly amplified polymorphic DNA PCR, a high-resolution biochemical
      fingerprinting method (PhP) and phylogenetic grouping were also used to identify
      the clonality of the sulphonamide-resistant isolates. One hundred and twenty
      (87.6 %) isolates were resistant to one or more of the tested antimicrobial
      drugs, with the highest resistance (70.1 %) observed against sulphafurazole (96
      isolates). Of these, 84 (87.5 %) contained one or more sul alleles, with sul1
      being the most common allele [occurring in 69 (72 %) isolates]. Only 38 of 69
      (55.1 %) strains carrying the sul1 gene were positive for class I integrase. Our
      results indicate a high prevalence of sulphafurazole-resistant UPEC strains
      belonging to different clones among patients with urinary tract infection in
      Queensland, Australia. We also conclude that these strains carry predominantly a
      sul1 gene that is not commonly associated with the presence of class I integrase,
      indicating that it may be carried on either a bacterial chromosome or other
      genetic elements.

PMID- 21737543
TI  - Genotypic and phenotypic characterization and clinical significance of
      'Haemophilus quentini' isolated from the urinary tract of adult men.
AB  - 'Haemophilus quentini' has been proposed as the name for a distinct and
      homogeneous Haemophilus genospecies associated with urogenital tract and neonatal
      related infections. Reports of 'H. quentini' isolation from adult men are rare
      and the disease potential in this population is unknown. We report six cases
      where 'H. quentini' was isolated from the genito-urinary tract in males. The
      isolation of 'H. quentini' during routine urine and urethral culture in adult men
      may aid in the determination of unresolved urethritis and possible urinary tract
      infections.

PMID- 21737544
TI  - Streptococcus australis meningitis.
AB  - We report a case of meningitis due to Streptococcus australis, a species of oral
      streptococcus. Accurate identification was performed by various molecular
      techniques.

PMID- 21737545
TI  - Septic arthritis due to a Sneathia species most closely related to Sneathia
      sanguinegens.
AB  - Sneathia sanguinegens is an infrequent bacterium in clinical specimens. We
      describe a case of right elbow septic arthritis due to a Sneathia species most
      closely related to S. sanguinegens in a young immunocompetent woman. S.
      sanguinegens has never been implicated in osteoarticular infections.

PMID- 21737546
TI  - Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin
      receptor expression.
AB  - Diabetic nephropathy (DN) increases podocyte cyclooxygenase-2 (COX-2) expression,
      and COX-2 inhibition reduces proteinuria and glomerular injury in animal models
      of diabetes. To investigate the role of podocyte COX-2 in development of diabetic
      nephropathy, we employed a streptozotocin model of diabetic mellitus in wild-type
      and transgenic mice expressing COX-2 selectively in podocytes. Progressive
      albuminuria developed only in diabetic COX-2 transgenic mice despite
      hyperglycemia, BP, and GFR being similar to those in wild-type mice. Transgenic
      mice also manifested significant foot-process effacement, moderate mesangial
      expansion, and segmental thickening of the glomerular basement membrane. In
      cultured podocytes overexpressing COX-2, high glucose induced cell injury and
      increased both expression of the pro(renin) receptor and activation of the renin
      angiotensin system. Downregulation of the (pro)renin receptor attenuated the
      injury induced by high glucose. In vivo, podocyte pro(renin) receptor expression
      increased in diabetic COX-2-transgenic mice, and treatment with a COX-2 inhibitor
      abrogated the upregulation of (pro)renin receptor and reduced albuminuria, foot
      process effacement, and mesangial matrix expansion. In summary, these results
      demonstrate that increased expression of podocyte COX-2 predisposes to diabetic
      glomerular injury and that the (pro)renin receptor may be one mediator for this
      increased susceptibility to injury.

PMID- 21737547
TI  - Surrogate markers predicting overall survival for lung cancer: ELCWP
      recommendations.
AB  - The present systematic review was performed under the auspices of the European
      Lung Cancer Working Party (ELCWP) in order to determine the role of early
      intermediate criteria (surrogate markers), instead of survival, in determining
      treatment efficacy in patients with lung cancer. Initially, the level of evidence
      for the use of overall survival to evaluate treatment efficacy was reviewed. Nine
      questions were then formulated by the ELCWP. After reviewing the literature with
      experts on these questions, it can be concluded that overall survival is still
      the best criterion for predicting treatment efficacy in lung cancer. Some
      intermediate criteria can be early predictors, if not surrogates, for survival,
      despite limitations in their potential application: these include time to
      progression, progression-free survival, objective response, local control after
      radiotherapy, downstaging in locally advanced nonsmall cell lung cancer (NSCLC),
      complete resection and pathological TNM in resected NSCLC, and a few circulating
      markers. Other criteria assessed in these recommendations are not currently
      adequate surrogates of survival in lung cancer.

PMID- 21737548
TI  - Strategies of muscle training in very severe COPD patients.
AB  - There is strong evidence that exercise training, constituting the cornerstone of
      pulmonary rehabilitation, improves exercise tolerance, dyspnoea sensations,
      functional capacity and quality of life in patients with severe chronic
      obstructive pulmonary disease. However, intolerable sensations of breathlessness
      and/or peripheral muscle discomfort may prevent such patients from tolerating
      high-intensity exercise levels for sufficiently long periods of time to obtain
      true physiological training effects. Accordingly, the major issue that arises is
      the selection of the appropriate training strategy, which is tailored to the
      cardiovascular, pulmonary and peripheral muscle limitations of the individual
      patient and is aimed at maximising the effect of exercise conditioning. Within
      this context, the present article explores the application of strategies that
      optimise exercise tolerance by reducing dyspnoea sensations, namely noninvasive
      mechanical ventilation, oxygen and/or heliox supplementation. Administration of
      heliox or oxygen during exercise also increases peripheral muscle oxygen
      delivery, thereby delaying the onset of peripheral muscle fatigue. Particular
      emphasis is also given to interval exercise and resistance-muscle training as
      both modalities allow the application of intense loads on peripheral muscles with
      tolerable levels of dyspnoea sensations. In patients with profound muscle
      weakness and intense breathlessness upon physical exertion, execution of short
      bouts of interval or local muscle strength conditioning, along with oxygen
      breathing, may constitute a feasible and effective approach to pulmonary
      rehabilitation.

PMID- 21737549
TI  - Tuberculosis and HIV co-infection in European Union and European Economic Area
      countries.
AB  - In order to ensure the availability of resources for tuberculosis (TB) and HIV
      management and control, it is imperative that countries monitor and plan for co
      infection in order to identify, treat and prevent TB-HIV co-infection, thereby
      reducing TB burden and increasing the years of healthy life of people living with
      HIV. A systematic review was undertaken to determine the burden of TB-HIV
      infection in the European Union (EU) and European Economic Area (EEA). Data on
      the burden of HIV infection in TB patients and risk factors for TB-HIV co
      infection in the EU/EEA were extracted from studies that collected information in
      1996 and later, regardless of the year of initiation of data collection, and a
      narrative synthesis presented. The proportion of HIV-co-infected TB patients
      varied from 0 to 15%. Western and eastern countries had higher levels and
      increasing trends of infection over time compared with central EU/EEA countries.
      Groups at higher risk of TB-HIV co-infection were males, young adults, foreign
      born persons, the homeless, injecting drug users and prisoners. Further research
      is needed into the burden and associated risk factors of co-infection in Europe,
      to help plan effective control measures. Increased HIV testing of TB patients and
      targeted and informed strategies for control and prevention could help curb the
      co-infection epidemic.

PMID- 21737550
TI  - Targeted gene delivery of BMPR2 attenuates pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) remains a fatal disease despite modern
      pharmacotherapy. Mutations in the gene for bone morphogenetic protein receptor
      type II (BMPR2) lead to reduced BMPR2 expression, which is causally linked to
      PAH. BMPR2 is predominantly expressed on pulmonary endothelium and has complex
      interactions with transforming growth factor (TGF)-beta signalling mechanisms.
      Our objectives were to assess the effect on PAH of upregulating BMPR2 by targeted
      adenoviral BMPR2 gene delivery to the pulmonary vascular endothelium. We used two
      established rat models of PAH: chronic hypoxia and monocrotaline (MCT). In both
      hypertensive models, those receiving BMPR2 had less right ventricular
      hypertrophy, less pulmonary vascular resistance, improved cardiac function and
      reduced vascular remodelling. In the MCT model, there was an increase in TGF
      beta, which was prevented by BMPR2 treatment. In vitro, TGF-beta1-induced
      endothelial-mesenchymal transition (EndMT) in human pulmonary microvascular
      endothelial cells, which was associated with reduced BMPR2 expression. EndMT was
      partially ameliorated by stimulating BMPR2 signalling with appropriate ligands
      even in the ongoing presence of TGF-beta1. Collectively, these results indicate
      therapeutic potential for upregulation of the BMPR2 axis in PAH, which may be, in
      part, mediated by countering the remodelling effects of TGF-beta.

PMID- 21737551
TI  - Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary
      fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterised by myofibroblast
      proliferation leading to architectural destruction. Neither the origin nor the
      continued proliferation of myofibroblasts is well understood. Explanted human IPF
      lungs were stained by immunohistochemistry for calretinin, a marker of pleural
      mesothelial cells (PMCs). Chronic obstructive pulmonary disease (COPD) and cystic
      fibrosis (CF) lungs acted as controls. The number of PMCs per 100 nucleated cells
      and per photomicrograph was estimated along with the Ashcroft score of fibrosis.
      Mouse PMCs expressing green fluorescent protein (GFP) or labelled with
      nanoparticles were injected into the pleural space of mice given intranasal
      transforming growth factor (TGF)-beta1. Mouse lungs were lavaged and examined for
      the presence of GFP, smooth muscle alpha-actin (alpha-SMA) and calretinin.
      Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF
      lungs. The number of PMCs correlated with the Ashcroft score. In mice,
      nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on
      the TGF-beta1 dose. Fluorescent staining showed alpha-SMA expression in GFP
      expressing PMCs, with co-localisation of GFP and alpha-SMA. PMCs can traffic
      through the lung and show myofibroblast phenotypic markers. PMCs are present in
      IPF lungs, and their number correlates with IPF severity. Since IPF presumably
      begins subpleurally, PMCs could play a pathogenetic role via mesothelial
      mesenchymal transition.

PMID- 21737552
TI  - Diagnosis of CTEPH versus IPAH using capillary to end-tidal carbon dioxide
      gradients.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) represents an important
      differential diagnosis to idiopathic pulmonary arterial hypertension (IPAH). We
      hypothesised that the capillary to end-tidal carbon dioxide gradient at rest and
      during exercise might help differentiate CTEPH from IPAH. Patients who presented
      with unequivocal IPAH or CTEPH according to ventilation/perfusion scanning,
      pulmonary angiography, computed tomography and right heart catheterisation were
      included in this retrospective study and compared with healthy controls. 21 IPAH
      patients and 16 CTEPH patients fulfilled the inclusion criteria. Haemodynamics
      and peak oxygen uptake were comparable, but respiratory rates at rest and during
      exercise were significantly higher in CTEPH than in IPAH. End-tidal carbon
      dioxide was significantly lower in CTEPH versus IPAH at rest and during exercise,
      while capillary carbon dioxide values were similar. Correspondingly, capillary to
      end-tidal carbon dioxide gradients were significantly increased in CTEPH versus
      IPAH at rest and during exercise (median (range) 8.6 (3.0-13.7) versus 4.4 (0.9
      9.0) (p<0.001) and 9.3 (3.3-13.1) versus 4.1 (0.0-8.8) mmHg (p<0.001),
      respectively). Although these values were closer to normal in IPAH they were
      still significantly elevated compared with healthy controls (2.3 (-4.8-8.1) and 
      1.9 (-5.7-6.2) mmHg, respectively). Capillary to end-tidal carbon dioxide
      gradients may help to distinguish CTEPH from IPAH based on resting and exercise
      values.

PMID- 21737553
TI  - Roflumilast with long-acting beta2-agonists for COPD: influence of exacerbation
      history.
AB  - The oral, selective phosphodiesterase type-4 inhibitor roflumilast reduces
      exacerbations and improves lung function in patients with severe-to-very severe
      chronic obstructive pulmonary disease (COPD). We investigated the efficacy and
      safety of roflumilast used concomitantly with long-acting beta(2)-agonists
      (LABAs) to reduce exacerbations, and the influence of exacerbation history.
      Pooled data were analysed from two 12-month, placebo-controlled roflumilast (500
      MUg once daily) studies involving 3,091 patients with severe-to-very severe COPD.
      Approximately half of patients used concomitant LABAs; 39% used concomitant short
      acting muscarinic antagonists (SAMAs); 27% were frequent exacerbators (two or
      more exacerbations per year). Roflumilast reduced the rate of moderate or severe
      exacerbations, with LABA (rate ratio (RR) 0.79, 95% CI 0.69-0.91; p=0.001) or
      without LABA (RR 0.85, 95% CI 0.74-0.99; p=0.039) and prolonged time both to
      first (p=0.035 with LABA, p=0.300 without LABA) and second (p=0.018 with LABA,
      p=0.049 without LABA) exacerbations. Frequent exacerbators experienced a
      reduction in moderate or severe exacerbations (RR 0.78, 95% CI 0.66-0.91;
      p=0.002). Similarly, roflumilast remained effective with concomitant SAMA. No
      differences arose in adverse events between these subgroups. Roflumilast may be
      used to reduce exacerbations and improve dyspnoea and lung function, without
      increasing adverse events in COPD patients receiving concomitant LABAs.

PMID- 21737554
TI  - Molecular genetics and clinical features of Chinese idiopathic and heritable
      pulmonary arterial hypertension patients.
AB  - Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene
      predispose to pulmonary arterial hypertension (PAH). 290 idiopathic (I)PAH
      patients and 15 heritable (H)PAH were screened to determine the spectrum and rate
      of BMPR2 mutations in a large Chinese patient group. Gene sequencing and
      multiplex ligation-dependent probe amplification (MLPA(r)) were used to detect
      sequence mutations and large rearrangements (RGTs). Total mutation rate was 14.5%
      (n = 42 out of 290) in Chinese IPAH patients, and 53.3% (n = 8 out of 15) in HPAH
      patients. RGT mutation rate was 3.1% (n = 7 out of 229) and represented 14% (n =
      7 out of 50) of all identified mutations. 25 BMPR2 mutations were newly
      identified. Patients in this study were younger than other reported PAH subjects.
      BMPR2 mutation carriers were ~6 yrs younger at diagnosis than noncarriers (p =
      0.002), but this relationship was significant only in the female group, which was
      larger. The proportion of females carrying a BMPR2 mutation was half that of
      males (12.8% versus 25.3%; p = 0.008). Our results indicate that the overall
      genetics of Chinese PAH patients is similar to that of other populations, but the
      clinical picture differs by the precocity of the disease in the whole patient
      group, and the lower proportion of females found to carry a BMPR2 mutation.

PMID- 21737555
TI  - Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.
AB  - The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary
      illness in a small number of exposed individuals. Our objective was to determine
      the influence of genetic factors on their susceptibility. We carried out a case
      control association study genotyping 91 patients with confirmed severe pneumonia
      from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using
      the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide
      polymorphisms were significantly (p<0.0001) associated with severe pneumonia:
      rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A)
      gene, chromosome 1; OR 2.68, 95% CI 1.69-4.25); rs9856661 (gene unknown,
      chromosome 3; OR 2.62, 95% CI 1.64-4.18); rs8070740 (RPA interacting protein
      (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63-4.39); and rs3786054
      (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome
      17; OR 3.13, 95% CI 1.89-5.17). All SNP associations remained significant after
      adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage
      disequilibrium. These findings revealed that gene polymorphisms located in
      chromosomes 1 and 17 might influence susceptibility to development of severe
      pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A,
      C1QBP) involved in the handling of immune complexes and complement activation,
      respectively, suggesting that these genes may confer risk due to increased
      activation of host immunity.

PMID- 21737556
TI  - Is community-acquired pneumonia an independent risk factor for cardiovascular
      disease?
AB  - Community-acquired pneumonia (CAP) is the most frequent infectious cause of death
      in western countries. The high mortality rate in CAP is commonly related to
      comorbid conditions such as cardiovascular disease. Clinical studies in both
      primary and secondary care settings have identified an increase in short- and
      long-term risk of cardiovascular events and death from vascular events following
      acute respiratory infections. The mechanism remains to be fully established, but
      it has been suggested that the inflammatory state in patients affected by CAP
      acts to promote platelet activation and thrombosis, and to narrow coronary
      arteries through vasoconstriction. Acute infections destabilise vascular
      endothelium and create an imbalance between myocardial oxygen supply and demand,
      leading to an increased risk of cardiovascular events. Acute infections have been
      shown to have both systemic effects and local effects on coronary vessels. These
      effects are mediated through both the host response to infection and, in some
      cases, direct effects of bacterial infection or bacterial products. In this
      review, we discuss the link between CAP and increased risk of cardiovascular
      events, drawing on existing evidence from clinical and mechanistic studies.
      Further studies into and increased awareness of this association is warranted to
      promote novel ways of protecting high-risk patients.

PMID- 21737557
TI  - Pharmacological treatment of severe, therapy-resistant asthma in children: what
      can we learn from where?
AB  - There is a lack of high-quality evidence on what treatment should be used in
      children with properly characterised severe, therapy-resistant asthma. Data have
      to be largely extrapolated from trials in children with mild asthma, and adults
      with severe asthma. Therapeutic options can be divided into medications used in
      lower doses for children with less severe asthma, and those used in other
      paediatric diseases but not for asthma (for example, methotrexate). In the first
      category are high-dose inhaled corticosteroids (ICS) (<= 2,000 MUg . day(-1)
      fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E
      antibody omalizumab, high-dose long-acting beta(2)-agonists, low-dose oral
      theophylline and intramuscular triamcinolone. If peripheral airway inflammation
      is thought to be a problem, the use of fine-particle ICS or low-dose oral
      corticosteroids may be considered. More experimental therapies include oral
      macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine,
      gold salts, intravenous infusions of Ig, subcutaneous beta(2)-agonist treatment
      and, in those sensitised to fungi, oral antifungal therapy with itraconazole or
      voriconazole. Those with recurrent severe exacerbations, particularly in the
      context of good baseline asthma control, are particularly difficult to treat;
      baseline control and lung function must be optimised with the lowest possible
      dose of ICS, and allergen triggers and exposures minimised. The use of high-dose
      ICS, leukotriene receptor antagonists or both at the time of exacerbations can be
      considered. There is no evidence regarding which therapeutic option to recommend.
      Better evidence is required for all these treatment options, underscoring the
      need for the international and co-ordinated approach which we have previously
      advocated.

PMID- 21737558
TI  - Predicting survival in malignant mesothelioma.
AB  - Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal
      disease attracting an increasing range of medical interventions and escalating
      healthcare costs. Changes in survival and the factors affecting survival of all
      patients ever diagnosed with MM in Western Australia over the past five decades
      and confirmed by the Western Australian Mesothelioma Registry to December 2005
      were examined. Sex, age, date and method of diagnosis, site of disease and
      histological type were recorded. Date of onset of symptoms and performance status
      were obtained from clinical notes for a sample of cases. Cox regression was used
      to examine the association of the clinical variables and the 10-yr periods of
      disease onset with survival after diagnosis. Survival was inversely related to
      age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2-1.6), and those
      with peritoneal mesothelioma (HR 1.4, 95% CI 1.1-1.7). Patients with sarcomatoid
      histology had worse prognosis than patients with epithelioid and biphasic
      histological subtypes. Survival improved after the 1970s and has made incremental
      improvements since then. Median (interquartile range) survival by decade, from
      1960 until 2005, was 64 (0-198), 177 (48-350), 221 (97-504), 238 (108-502) and
      301 (134-611) days; ~4 weeks of this apparent improvement can be attributed to
      earlier diagnosis. With increasing resources and treatment costs for MM over the
      past 40 yrs, there have been modest improvements in survival but no complete
      remissions.

PMID- 21737559
TI  - Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease.
AB  - Recent epidemiological studies have suggested an increased risk of venous
      thromboembolism (VTE) in lung fibrosis. Large-scale epidemiological data
      regarding the risk of VTE in pulmonary fibrosis-associated mortality have not
      been published. Using data from the National Center for Health Statistics from
      1988-2007, we determined the risk of VTE in decedents with pulmonary fibrosis in
      the USA. We analysed 46,450,489 records, of which 218,991 met our criteria for
      idiopathic pulmonary fibrosis. Among these, 3,815 (1.74%) records also contained
      a diagnostic code for VTE. The risk of VTE in pulmonary fibrosis decedents was
      34% higher than in the background population, and 44% and 54% greater than among
      decedents with chronic obstructive pulmonary disease and lung cancer,
      respectively. Those with VTE and pulmonary fibrosis died at a younger age than
      those with pulmonary fibrosis alone (females: 74.3 versus 77.4 yrs (p<0.0001);
      males: 72.0 versus 74.4 yrs (p<0.0001)). Decedents with pulmonary fibrosis had a
      significantly greater risk of VTE. Those with VTE and pulmonary fibrosis died at
      a younger age than those with pulmonary fibrosis alone. These data suggest a link
      between a pro-fibrotic and a pro-coagulant state.

PMID- 21737560
TI  - Improved treatment response to dornase alfa in cystic fibrosis patients using
      controlled inhalation.
AB  - Better treatment of obstructed small airways is needed in cystic fibrosis. This
      study investigated whether efficient deposition of dornase alfa in the small
      airways improves small airway obstruction. In a multicentre, double-blind,
      randomised controlled clinical trial, cystic fibrosis patients on maintenance
      treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser
      and randomised to small airway deposition (n = 24) or large airway deposition (n
      = 25) for 4 weeks. The primary outcome parameter was forced expiratory flow at
      75% of forced vital capacity (FEF(75%)). FEF(75%) increased significantly by 0.7
      sd (5.2% predicted) in the large airways group and 1.2 sd (8.8% pred) in the
      small airways group. Intention-to-treat analysis did not show a significant
      difference in treatment effect between groups. Per-protocol analysis, excluding
      patients not completing the trial or with adherence <70%, showed a trend (p =
      0.06) in FEF(75%) Z-score and a significant difference (p = 0.04) between groups
      in absolute FEF(75%) (L . s(-1)) favouring small airway deposition. Improved
      delivery of dornase alfa using a smart nebuliser that aids patients in correct
      inhalation technique resulted in significant improvement of FEF(75%) in children
      with stable cystic fibrosis. Adherent children showed a larger treatment response
      for small airway deposition.

PMID- 21737561
TI  - Seasonality and determinants of moderate and severe COPD exacerbations in the
      TORCH study.
AB  - We investigated the impact of season relative to other determinants of chronic
      obstructive pulmonary disease (COPD) exacerbation frequency in a long-term
      international study of patients with forced expiratory volume in 1 s (FEV(1))
      <60% predicted. COPD exacerbations were defined by worsening symptoms requiring
      systemic corticosteroids and/or antibiotics (moderate) or hospital admission
      (severe). Seasonality effect was calculated as the proportion of patients
      experiencing an exacerbation each month. Exacerbations in the northern and
      southern regions showed an almost two-fold increase in the winter months. No
      seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were
      treated with antibiotics only, 19% with systemic corticosteroids only and 43%
      with both, while 20% required hospital admission irrespective of the season.
      Exacerbation frequency was associated with older age, lower body mass index,
      lower FEV(1) % pred and history of prior exacerbations. Females and patients with
      worse baseline breathlessness, assessed using the Medical Research Council (MRC)
      dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female
      0.7, 95% CI 0.7-0.8 (p<0.001); RR for MRC dyspnoea score 3 versus 1 and 2
      combined 1.1, 95% CI 1.1-1.2 (p<0.001)). The effect of season was independent of
      these risk factors. COPD exacerbations and hospitalisations were more frequent in
      winter.

PMID- 21737562
TI  - The association between resting and mild-to-moderate exercise pulmonary artery
      pressure.
AB  - The mean pulmonary artery pressure (P(pa)) achieved on mild-to-moderate exercise
      is age related and its haemodynamic correlates remain to be documented in
      patients free of pulmonary hypertension (PH). Our retrospective study involved
      patients free of PH investigated in our centre for possible pulmonary vascular
      disease between January 1, 2007 and October 31, 2009 who underwent right heart
      catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99
      patients aged <50 yrs were included and a P(pa) of 30 mmHg was considered the
      upper limit of normal on exercise. The 24 subjects who developed P(pa)>30 mmHg on
      exercise had higher resting P(pa) (19+/-3 versus 15+/-4 mmHg) and indexed
      pulmonary vascular resistance (PVRi; 3.4+/-1.5 versus 2.2+/-1.1 WU.m(2); p<0.05)
      than the remaining 14 subjects. Resting P(pa) >15 mmHg predicted exercise P(pa)
      >30 mmHg with 88% sensitivity and 57% specificity. The eight patients with
      resting P(pa) 22-24 mmHg all had exercise P(pa) >30 mmHg. In subjects aged <50
      yrs investigated for possible pulmonary vascular disease and free of PH, patients
      with mild-to-moderate exercise P(pa) >30 mmHg had higher resting PVRi and higher
      resting P(pa), although there was no resting P(pa) threshold value that could
      predict normal response on mild-to-moderate exercise. The clinical relevance of
      such findings deserves further long-term follow-up studies.

PMID- 21737563
TI  - Prevalence of hiatal hernia by blinded multidetector CT in patients with
      idiopathic pulmonary fibrosis.
AB  - Hiatal hernia (HH) is associated with gastro-oesophageal reflux (GOR) and/or GOR
      disease and may contribute to idiopathic pulmonary fibrosis (IPF). We
      hypothesised that HH evaluated by computed tomography is more common in IPF than
      in asthma or chronic obstructive pulmonary disease (COPD), and correlates with
      abnormal GOR measured by pH probe testing. Rates of HH were compared in three
      cohorts, IPF (n=100), COPD (n=60) and asthma (n=24), and evaluated for inter
      observer agreement. In IPF, symptoms and anti-reflux medications were correlated
      with diffusing capacity of the lung for carbon monoxide (D(L,CO)) and composite
      physiologic index (CPI). HH was correlated with pH probe testing in IPF patients
      (n=14). HH was higher in IPF (39%) than either COPD (13.3%, p=0.00009) or asthma
      (16.67%, p=0.0139). The HH inter-observer kappa agreement was substantial in IPF
      (kappa=0.78) and asthma (kappa=0.86), and moderate in COPD (kappa=0.42). In IPF,
      HH did not correlate with lung function, except in those on anti-reflux therapy,
      who had a better D(L,CO) (p<0.03) and CPI (p<0.04). HH correlated with GOR as
      measured by DeMeester scores (p<0.04). HH is more common in IPF than COPD or
      asthma. In an IPF cohort, HH correlated with higher DeMeester scores, confirming
      abnormal acid GOR. Presence of HH alone was not associated with decreased lung
      function.

PMID- 21737564
TI  - Impact of cigarette smoke exposure on host-bacterial pathogen interactions.
AB  - The human respiratory tract of individuals with normal lung function maintains a
      fine-tuned balance, being asymptomatically colonised by the normal microbiota in
      the upper airways and sterile in the lower tract. This equilibrium may be
      disrupted by the exposure to insults such as cigarette smoke. In the respiratory
      tract, the complex and noxious nature of inhaled cigarette smoke alters host
      microorganism interaction dynamics at all anatomical levels, causing infections
      in many cases. Moreover, continuous exposure to cigarette smoke itself causes
      deleterious effects on the host that can trigger the development of chronic
      respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and
      lung cancer. COPD is an irreversible airflow obstruction associated with
      emphysema, fibrosis, mucus hypersecretion and persistent colonisation of the
      lower airways by opportunistic pathogens. COPD patients keep a stable (without
      exacerbation) but progressively worsening condition and suffer periodic
      exacerbations caused, in most cases, by infections. Although smoking and smoking
      associated diseases are associated with a high risk of infection, most therapies
      aim to reduce inflammatory parameters, but do not necessarily take into account
      the presence of persistent colonisers. The effect of cigarette smoke on host
      pathogen interaction dynamics in the respiratory tract, together with current and
      novel therapies, is discussed.

PMID- 21737565
TI  - Trajectories of endurance activity following pulmonary rehabilitation in COPD
      patients.
AB  - Maintenance of physical activity following pulmonary rehabilitation remains a
      challenge for patients with chronic obstructive pulmonary disease (COPD). The
      objectives of this study were to identify patterns of endurance activity after
      completion of pulmonary rehabilitation and to characterise people who succeed and
      those who have difficulty maintaining endurance activity. In a longitudinal study
      embedded within a randomised clinical trial, 206 individuals with COPD underwent
      a 3-month pulmonary rehabilitation programme. Weekly duration of endurance
      activity was assessed at 4, 6, 8 and 12 months after the start of rehabilitation.
      Trajectory modelling was used to determine the most common patterns of activity
      during the post-rehabilitation phase from 4-12 months. Three distinct patterns
      were identified, two of which indicated difficulty in maintaining endurance
      activity: 61 individuals reported a high activity level at 4 months (2.7 h.week(
      1)) and stayed high; 114 individuals started at a low activity level (mean 1.0
      h.week(-1)) and stayed low; and 31 individuals started high (3.0 h.week(-1)) and
      declined. The low activity group was characterised by more severe disease and
      greater respiratory impairment. The high and declined group had less severe
      disease and respiratory impairment, but reported greater barriers to exercise.
      Pulmonary rehabilitation should include interventions aimed at minimising
      barriers, in order to induce long-term behaviour change.

PMID- 21737566
TI  - Analysis of global and absorption, distribution, metabolism, and elimination gene
      expression in the progressive stages of human nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is characterized by a series of
      pathological changes that range from simple fatty liver to nonalcoholic
      steatohepatitis (NASH). The objective of this study is to describe changes in
      global gene expression associated with the progression of human NAFLD. This study
      is focused on the expression levels of genes responsible for the absorption,
      distribution, metabolism, and elimination (ADME) of drugs. Differential gene
      expression between three clinically defined pathological groups-normal,
      steatosis, and NASH-was analyzed. Genome-wide mRNA levels in samples of human
      liver tissue were assayed with Affymetrix GeneChip Human 1.0ST arrays. A total of
      11,633 genes exhibited altered expression out of 33,252 genes at a 5% false
      discovery rate. Most gene expression changes occurred in the progression from
      steatosis to NASH. Principal component analysis revealed that hepatic disease
      status was the major determinant of differential ADME gene expression rather than
      age or sex of sample donors. Among the 515 drug transporters and 258 drug
      metabolizing enzymes (DMEs) examined, uptake transporters but not efflux
      transporters or DMEs were significantly over-represented in the number of genes
      down-regulated. These results suggest that uptake transporter genes are
      coordinately targeted for down-regulation at the global level during the
      pathological development of NASH and that these patients may have decreased drug
      uptake capacity. This coordinated regulation of uptake transporter genes is
      indicative of a hepatoprotective mechanism acting to prevent accumulation of
      toxic intermediates in disease-compromised hepatocytes.

PMID- 21737567
TI  - Clearance and biodistribution of liposomally encapsulated nitroxides: a model for
      targeted delivery of electron paramagnetic resonance imaging probes to tumors.
AB  - Electron paramagnetic resonance (EPR) imaging using nitroxides as molecular
      probes is potentially a powerful tool for the detection and physiological
      characterization of micrometastatic lesions. Encapsulating nitroxides in anti
      HER2 immunoliposomes at high concentrations to take advantage of the "self
      quenching" phenomenon of nitroxides allows generation of robust EPR signals in
      HER2-overexpressing breast tumor cells with minimal background from indifferent
      tissues or circulating liposomes. We investigated the in vivo pharmacological
      properties of nitroxides encapsulated in sterically stabilized liposomes designed
      for long circulation times. We show that circulation times of nitroxides can be
      extended from hours to days; this increases the proportion of liposomes in
      circulation to enhance tumor targeting. Furthermore, nitroxides encapsulated in
      sterically stabilized anti-HER2 immunoliposomes can be delivered to HER2
      overexpressing tumors at micromolar concentrations, which should be imageable by
      EPR. Lastly, after in vivo administration, liposomally encapsulated nitroxide
      signal also appears in the liver, spleen, and kidneys. Although these organs are
      spatially distinct and would not hinder tumor imaging in our model, understanding
      nitroxide signal retention in these organs is essential for further improvements
      in EPR imaging contrast between tumors and other tissues. These results lay the
      foundation to use liposomally delivered nitroxides and EPR imaging to visualize
      tumor cells in vivo.

PMID- 21737568
TI  - Interviewing separately or as couples? Considerations of authenticity of method.
AB  - Heideggerian researchers recognize that people and their worlds are
      coconstructed; people make sense of their world from within it, not detached from
      it. The presence of one's partner in a joint interview will therefore influence
      the experience of participants, and will also influence the descriptions they
      provide. In this article, we present a reflexive discussion of two studies in
      which we used Heideggerian hermeneutic phenomenology to explore people's
      experiences of sexuality and intimacy within the context of their illness. We
      present the Heideggerian concepts of Dasein, authenticity and truth, and draw on
      extracts from our interview transcripts to exemplify the different effects of
      joint and one-to-one interviews. We also discuss ethical considerations regarding
      these different interview approaches. Heidegger's philosophy does not
      preferentially support either method, but helps us to be clearer about the merits
      and limitations of each approach. Combining both approaches provides richer
      understanding of phenomena.

PMID- 21737569
TI  - Understanding molecular recognition by G protein betagamma subunits on the path
      to pharmacological targeting.
AB  - Heterotrimeric G proteins, composed of Galpha and Gbetagamma subunits, transduce
      extracellular signals via G-protein-coupled receptors to modulate many important
      intracellular responses. The Gbetagamma subunits hold a central position in this
      signaling system and have been implicated in multiple aspects of physiology and
      the pathophysiology of disease. The Gbeta subunit belongs to a large family of
      WD40 repeat proteins with a circular beta-bladed propeller structure. This
      structure allows Gbetagamma to interact with a broad range of proteins to play
      diverse roles. How Gbetagamma interacts with and regulates such a wide variety of
      partners yet maintains specificity is an interesting problem in protein-protein
      molecular recognition in signal transduction, where signal transfer by proteins
      is often driven by modular conserved recognition motifs. Evidence has accumulated
      that one mechanism for Gbetagamma multitarget recognition is through an
      intrinsically flexible protein surface or "hot spot" that accommodates multiple
      modes of binding. Because each target has a unique recognition mode for
      Gbetagamma subunits, it suggests that these interactions could be selectively
      manipulated with small molecules, which could have significant therapeutic
      potential.

PMID- 21737570
TI  - MicroRNAs: new players in cardiac injury and protection.
AB  - MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, noncoding
      RNAs that negatively regulate gene expression via degradation or translational
      inhibition of their target mRNAs. Over 700 miRNAs have been identified and
      sequenced in humans, and the number of miRNA genes is estimated at more than
      1000. Individual miRNA is functionally important as a transcription factor
      because it has the ability to regulate the expression of multiple genes through
      binding to its target with imperfect or perfect complement. In the heart, miRNAs
      have been involved in several clinical scenarios, such as ischemia/reperfusion
      (I/R) injury and heart failure suggesting that regulation of their function could
      be used as a novel cardioprotective strategy. In particular, miRNA-1, miRNA-21,
      miRNA-24, miRNA-29, miRNA-92a, miRNA-126, miRNA-133, miRNA-320, miRNA-199a, miRNA
      208, and miRNA-195 have been shown to be regulated after I/R injury. Because
      tissue miRNAs can be released into circulating blood, they also offer exciting
      new opportunities for developing sensitive biomarkers, including miRNA-1, miRNA
      126, miR-208, and miRNA-499, for acute myocardial infarction and other cardiac
      diseases.

PMID- 21737571
TI  - The antiepileptic drugs phenobarbital and carbamazepine reduce transport of
      methotrexate in rat choroid plexus by down-regulation of the reduced folate
      carrier.
AB  - Intrathecal methotrexate (MTX) has been associated with severe neurotoxicity.
      Because carrier-associated removal of MTX from the cerebrospinal fluid (CSF) into
      blood remains undefined, we determined the expression and function of MTX
      transporters in rat choroid plexus (CP). MTX neurotoxicity usually manifests as
      seizures requiring therapy with antiepileptic drugs (AEDs) such as phenobarbital
      (PB). Because we have demonstrated that PB reduces activity of MTX influx carrier
      reduced folate carrier (Rfc1) in liver, we investigated the influence of the AEDs
      PB, carbamazepine (CBZ), or gabapentin on Rfc1-mediated MTX transport in CP.
      Reverse transcriptase-polymerase chain reaction and Western blot analysis showed
      similar expression of the MTX influx carrier Rfc1 and organic anion transporter 3
      or efflux transporter multidrug resistance-associated protein 1 (Mrp1) and breast
      cancer resistance protein (Bcrp) in rat CP tissue and choroidal epithelial Z310
      cells. Confocal microscopy revealed subcellular localization of Rfc1 and Bcrp at
      the apical and of Mrp1 at the basolateral CP membrane. Uptake, efflux, and
      inhibition studies indicated MTX transport activity of Rfc1, Mrp1, and Bcrp. PB
      and CBZ but not gabapentin significantly inhibited Rfc1-mediated uptake of MTX in
      CP cells. Studies on the regulatory mechanism showed that PB significantly
      inhibited Rfc1 translation but did not alter carrier gene expression. Altogether,
      removal of intrathecal MTX across the blood-CSF barrier may be achieved through
      Rfc1-mediated uptake from the CSF followed by MTX extrusion into blood,
      particularly via Mrp1. Antiepileptic treatment with PB or CBZ causes post
      transcriptional down-regulation of Rfc1 activity in CP. This mechanism may result
      in enhanced MTX toxicity in patients with cancer who are receiving intrathecal
      MTX chemotherapy by reduced CSF clearance of the drug.

PMID- 21737572
TI  - The selective estrogen receptor modulator bazedoxifene inhibits hormone
      independent breast cancer cell growth and down-regulates estrogen receptor alpha
      and cyclin D1.
AB  - Bazedoxifene (BZA) is a third-generation selective estrogen receptor modulator
      (SERM) that has been approved for the prevention and treatment of postmenopausal
      osteoporosis. It has antitumor activity; however, its mechanism of action remains
      unclear. In the present study, we characterized the effects of BZA and several
      other SERMs on the proliferation of hormone-dependent MCF-7 and T47D breast
      cancer cells and hormone-independent MCF-7:5C and MCF-7:2A cells and examined its
      mechanism of action in these cells. We found that all of the SERMs inhibited the
      growth of MCF-7, T47D, and MCF-7:2A cells; however, only BZA and fulvestrant
      (FUL) inhibited the growth of hormone-independent MCF-7:5C cells. Cell cycle
      analysis revealed that BZA and FUL induced G(1) blockade in MCF-7:5C cells;
      however, BZA down-regulated cyclin D1, which was constitutively overexpressed in
      these cells, whereas FUL suppressed cyclin A. Further analysis revealed that
      small interfering RNA knockdown of cyclin D1 reduced the basal growth of MCF-7:5C
      cells, and it blocked the ability of BZA to induce G(1) arrest in these cells.
      BZA also down-regulated estrogen receptor-alpha (ERalpha) protein by increasing
      its degradation and suppressing cyclin D1 promoter activity in MCF-7:5C cells.
      Finally, molecular modeling studies demonstrated that BZA bound to ERalpha in an
      orientation similar to raloxifene; however, a number of residues adopted
      different conformations in the induced-fit docking poses compared with the
      experimental structure of ERalpha-raloxifene. Together, these findings indicate
      that BZA is distinct from other SERMs in its ability to inhibit hormone
      independent breast cancer cell growth and to regulate ERalpha and cyclin D1
      expression in resistant cells.

PMID- 21737573
TI  - Spontaneous trait inference is culture-specific: behavioral and neural evidence.
AB  - People with an independent model of the self may be expected to develop a
      spontaneous tendency to infer a personality trait from another person's behavior,
      but those with an interdependent model of the self may not show such a tendency.
      We tested this prediction by assessing the cumulative effect of both trait
      activation and trait binding in a diagnostic task that required no trait
      inference. Participants first memorized pairings of facial photos with trait
      implying behavior. In a subsequent lexical decision task, European Americans
      showed clear evidence of spontaneous trait inference: When they were primed with
      a previously studied face, lexical decision for the word for the implied trait
      associated with that face was facilitated, and the antonym of the implied trait
      elicited an electrophysiological sign associated with processing of semantically
      inconsistent information (i.e., the N400). As predicted, however, neither effect
      was observed for Asian Americans. The cultural difference was mediated by
      independent self-construal.

PMID- 21737574
TI  - Depression and empathic accuracy in couples: an interpersonal model of gender
      differences in depression.
AB  - We examine the link between depression and empathic accuracy, the ability to
      infer other people's thoughts and feelings, as a possible mechanism underlying
      gender differences in the association between depression and interpersonal
      difficulties within intimate relationships. Fifty-one heterosexual couples
      completed questionnaires assessing depressive symptoms and participated in both a
      lab and a daily diary procedure assessing empathic accuracy. In the lab measures,
      women's (but not men's) higher levels of depressive symptoms were associated with
      lower empathic accuracy regarding partners' thoughts and feelings. In the daily
      diary data, women's depressive symptoms were specifically associated with lower
      levels of empathic accuracy for negative feelings but not for positive feelings,
      and with lower levels of their partners' empathic accuracy for the women's
      negative feelings. Men's depressive symptoms were again unrelated to levels of
      empathic accuracy. Our findings suggest that depressive symptoms may have a
      stronger impact on interpersonal perception in intimate relationships among women
      than among men.

PMID- 21737575
TI  - Cardiovascular complications of breast cancer therapy in older adults.
AB  - Older adults frequently have pre-existing and cancer-related risk factors for
      cardiovascular toxicity from cancer treatment. In this review, we discuss the
      risk factors and strategies for prevention and management of cardiovascular
      complications in older women with breast cancer.

PMID- 21737576
TI  - The novel member of the BCL2 gene family, BCL2L12, is substantially elevated in
      chronic lymphocytic leukemia patients, supporting its value as a significant
      biomarker.
AB  - BCL2L12 is a recently identified gene belonging to the BCL2 family, members of
      which are implicated in hematologic malignancies, including chronic lymphocytic
      leukemia (CLL). The aim of this study was to analyze the mRNA expression of the
      novel apoptosis-related gene BCL2L12 in patients with CLL and to examine its
      prognostic and predictive value and potential clinical application as a novel
      molecular biomarker for CLL. For this purpose, total RNA was isolated from
      peripheral blood of 65 CLL patients and 23 healthy donors. An ultrasensitive
      quantitative real-time polymerase chain reaction methodology for BCL2L12 and BCL2
      mRNA quantification was developed using SYBR Green chemistry. After preparing
      cDNA by reverse transcription, relative quantification analysis was performed
      using the comparative C(T) (2(-DeltaDeltaCT)) method. Furthermore, analysis of
      IGHV mutational status, CD38 expression, and detection of early apoptosis by
      double staining with Annexin V-FITC and propidium iodide were performed.
      According to our findings, BCL2L12 mRNA expression is significantly higher in CLL
      patients than in healthy donors. Receiver operating characteristic analysis
      demonstrated that BCL2L12 expression had significant discriminatory value,
      distinguishing very efficiently CLL patients from the non-leukemic population.
      Moreover, BCL2L12 expression predicts the presence of CLL, as demonstrated by
      both univariate and multivariate logistic regression analyses. Finally, high
      BCL2L12 mRNA levels are associated with advanced clinical stage and predict
      shorter overall survival in CLL patients.

PMID- 21737577
TI  - KRAS and colorectal cancer: ethical and pragmatic issues in effecting real-time
      change in oncology clinical trials and practice.
AB  - Systemic therapy has led to a median survival time for patients with advanced
      colorectal cancer (CRC) almost fourfold longer than that expected with best
      supportive care, an outcome achieved through combining chemotherapeutic and
      targeted biologic agents. Although the latter can include anti-epidermal growth
      factor receptor antibodies, such as cetuximab and panitumumab, we now have strong
      evidence that patients whose tumors harbor mutated KRAS will not benefit from
      this class of agent. Acceptance of the reliability and importance of the KRAS
      data took several years to evolve, however, for a variety of reasons. The
      timeline from the presentation and publication of small, retrospective phase II
      studies to widespread acceptance of the KRAS predictive value and changes in
      behavior-specifically, modifications of ongoing national trials in
      advanced/metastatic CRC, changes in national guidelines and practice patterns,
      and adjustments to the labeled indications for the monoclonal antibodies-was
      lengthy. In this commentary, we discuss whether or not the process of data
      disclosure regarding KRAS status and treatment of advanced CRC patients was
      effective in permitting timely decisions regarding ongoing publicly funded
      clinical trials and whether or not such decisions were rational and ethical. The
      overall goals are to highlight lessons learned regarding early disclosure of
      clinical trial results, as well as vetting and adoption of new scientific data,
      and to propose modifications for handling similar situations in the future.

PMID- 21737578
TI  - The role of climate variability and change in the transmission dynamics and
      geographic distribution of dengue.
AB  - The mounting evidence for anthropogenic changes in global climate raises many
      pressing questions about the potential effects on biological systems, and in
      particular the transmission of infectious diseases. Vector-borne diseases, such
      as dengue, may be particularly sensitive to both periodic fluctuations and
      sustained changes in global and local climates, because vector biology and viral
      replication are temperature- and moisture-dependent. This paper reviews the
      current state of knowledge on the associations between climate variability,
      climate change and dengue transmission, and the tools being used to quantify
      these associations. The underlying causes of dengue's recent global expansion are
      multifactorial and poorly understood, but climatic factors should be considered
      within the context of the sociodemographic, economic and immunological
      determinants that have contributed to dengue's spread. These factors may mediate
      the direct effects of climate on dengue and many may operate at a very local
      level. Translating theoretical models of dengue transmission based on historical
      data into predictive models that can inform public health interventions is a
      critical next step and efforts should be focused on developing and refining
      models at smaller spatial scales to characterize the relationships between both
      climatic and non-climatic factors and dengue risk.

PMID- 21737579
TI  - Emerging and neglected tropical diseases: translational application of
      proteomics.
AB  - The challenges of identifying and controlling emerging diseases impact individual
      health, as well as political, social and economic situations. In this review we
      discuss the role of proteomics for investigation of pathogen discovery, outbreak
      investigation, bio-defense, disease control, host-pathogen dynamics and vaccine
      development of emerging and neglected tropical diseases (NTDs). In the future the
      discipline of proteomics may help define multiple aspects of emerging and NTDs
      with respect to personalized medicine and public health.

PMID- 21737580
TI  - Metagenomic analysis of bacterial infections by means of high-throughput DNA
      sequencing.
AB  - DNA sequencing technology has undergone a remarkable and continuous improvement
      in recent years. The so-called 'high-throughput DNA sequencers' can determine
      hundreds of megabases of DNA sequences per run. We have been applying these new
      sequencers to the analysis of infectious diseases, especially bacterial
      infections. We review the efficacy of these sequencers, mainly based on our own
      experiences. The approach described here can be viewed as a metagenomic analysis
      of infectious diseases. The approach is in principle a method that does not
      depend on the type of target pathogens, so that it is possible to analyze various
      microorganisms, including bacteria, viruses, fungi and parasites, with a single
      common protocol. Applying this novel approach to cases in which infectious
      diseases are suspected because of environmental evidence, but the causative agent
      has not been identified, may lead to the discovery of unknown, novel pathogens.
      Also, the approach enables us to conduct an unbiased analysis of dynamics of the
      pathogen and associated microbiota in human specimens during the course of
      infectious diseases.

PMID- 21737581
TI  - Diffusion-weighted MRI determined cerebral embolic infarction following
      transcatheter aortic valve implantation: assessment of predictive risk factors
      and the relationship to subsequent health status.
AB  - BACKGROUND: 'Silent' cerebral infarction and stroke are complications of
      transcatheter aortic valve implantation (TAVI). OBJECTIVE: To assess the
      occurrence of cerebral infarction, identify predictive risk factors and examine
      the impact on patient health-related quality of life (HRQoL). METHODS: Cerebral
      diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve
      TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2
      and EQ5D questionnaires. RESULTS: New cerebral infarcts occurred in 24/31
      patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number
      and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma
      (arch and descending aorta; r=0.91, p<0.001, r=0.69, p=0.001, respectively) and
      catheterisation time (r=0.45, p=0.02) were predictors of the number of new
      cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary
      increased significantly (32.4+/-6.2 vs 36.5+/-7.2; p=0.03) with no significant
      change in mental component summary (43.5+/-11.7 vs. 43.1+/-14.3; p=0.85). The
      EQ5D score and Visual Analogue Scale showed no significant change (0.56+/-0.26
      vs. 0.59+/-0.31; p=0.70, and 54.2+/-19 vs. 58.2+/-24; p=0.43). CONCLUSION:
      Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The
      majority of infarcts were 'silent' with clinical stroke being associated with a
      both higher infarct number and volume. Increased age and the severity of aortic
      arch atheroma were independent risk factors for the development of new cerebral
      infarcts. Overall HRQoL improved and there was no association between the number
      of new cerebral infarcts and altered health status.

PMID- 21737582
TI  - Contrast-induced nephropathy in primary percutaneous coronary intervention.

PMID- 21737583
TI  - Titration of antihypertensive agents after their initiation: an important
      clinical issue now addressed.

PMID- 21737584
TI  - Therapeutic decision-making for sleep apnea and hypopnea syndrome using home
      respiratory polygraphy: a large multicentric study.
AB  - RATIONALE: Home respiratory polygraphy (HRP) is an alternative to polysomnography
      (PSG) for sleep apnea-hypopnea syndrome (SAHS) diagnosis. However, therapeutic
      decision-making is a different process than diagnosis. OBJECTIVES: This study
      aimed to determine the agreement between HRP and in-hospital PSG for therapeutic
      decision-making in a large sample. METHODS: Patients with an intermediate or high
      SAHS suspicion were included in a multicenter study (eight sleep centers) and
      assigned to home and hospital protocols in a random order. Therapeutic decisions
      (continuous positive airway pressure, no continuous positive airway pressure, or
      impossible decision) were made by an investigator in each center, based on using
      either HRP or PSG and a single set of auxiliary clinical variables. Patients and
      diagnostic methods (HRP and PSG) were assessed in random order using an
      electronic database. After a month the same therapeutic decision-making procedure
      was repeated with the same method. MEASUREMENTS AND MAIN RESULTS: Of 366
      randomized patients, 348 completed the protocol. The "impossible decision" case
      was not observed with either PSG or HRP. Therapeutic decisions using HRP had a
      sensitivity of 73%, a specificity of 77%, and an agreement level (sum of true
      positives and negatives) of 76%. Patients with higher HRP apnea-hypopnea index
      (AHI) scores (>= 30; 41% of the total sample) had a sensitivity of 94%, a
      specificity of 44%, and the agreement level was 91%. CONCLUSIONS: The HRP-based
      therapeutic decision was adequate when AHI was high, but deficient in the large
      population of patients with mild to moderate AHI. Therefore, both selecting
      patients with a high suspicion and severity of SAHS and future prospective cost
      effectiveness studies are necessary.

PMID- 21737585
TI  - CDC/NIH Workshop. Tuberculosis biomarker and surrogate endpoint research roadmap.
AB  - The Centers for Disease Control and Prevention and National Institutes of Health
      convened a multidisciplinary meeting to discuss surrogate markers of treatment
      response in tuberculosis. The goals were to assess recent surrogate marker
      research and to provide specific recommendations for (1) the qualification and
      validation of biomarkers of treatment outcome; (2) the standardization of
      specimen and data collection for future clinical trials, including a minimum set
      of samples and collection time points; and (3) the creation ofa specimen
      repository to support biomarker testing. This article summarizes these
      recommendations and provides a roadmap for their implementation.

PMID- 21737586
TI  - Chest computed tomography scores of severity are associated with future lung
      disease progression in children with cystic fibrosis.
AB  - RATIONALE: Most children with cystic fibrosis (CF) experience a slow decline in
      spirometry, although some children continue to be at risk for more significant
      lung disease progression. Chest computed tomography (CT) scans have been shown to
      be more sensitive to changes in lung disease than spirometry and may provide a
      means for predicting future lung disease progression. OBJECTIVES: We hypothesized
      that Brody chest CT scan scores obtained in 2000 in a prospectively monitored
      cohort of children with CF would be associated with the most recent measures of
      lung disease severity. METHODS: Brody chest CT scan scores were calculated for 81
      children enrolled in the Wisconsin CF Neonatal Screening Project. Multivariable
      linear regression was used to determine associations between Brody scores and the
      most recent (age 21 yr or June 30, 2010, whichever was later) measures of CF lung
      disease. MEASUREMENTS AND MAIN RESULTS: The mean observation time after the chest
      CT scan was 7.5 years. Brody chest CT scan scores were significantly associated
      with the most recent measures of spirometry (P < 0.001) and Wisconsin and
      Brasfield chest radiograph scores (P < 0.001). The strength of this association
      was much stronger than spirometry obtained near the time of the chest CT scan (P
      < 0.01) but not chest radiograph scores. CONCLUSIONS: Chest CT scan scores are
      associated with future lung disease severity, and quantitative chest
      imaging(chest CT scan and chest radiograph scores) is more strongly associated
      with future lung disease severity than measures of spirometry. These findings may
      help clinicians identify patients at risk of future lung disease progression.

PMID- 21737587
TI  - The ever-expanding role of prostanoids in regulating immune responses.

PMID- 21737588
TI  - Vocal cord dysfunction and severe asthma: considering the total airway.

PMID- 21737589
TI  - End of an ERA: lessons from negative clinical trials in idiopathic pulmonary
      fibrosis.

PMID- 21737590
TI  - Emerging role of c-kit+ progenitor cells in pulmonary hypertension.

PMID- 21737591
TI  - Update on pulmonary vascular diseases 2010.

PMID- 21737592
TI  - Update in mechanical ventilation 2010.

PMID- 21737593
TI  - Bilateral pulmonary sequestration.

PMID- 21737594
TI  - Limits of neutrophil gelatinase-associated lipocalin at intensive care unit
      admission for prediction of acute kidney injury.

PMID- 21737595
TI  - Rationalizing the use of NGAL in the intensive care unit.

PMID- 21737596
TI  - The CRP and GDNF genes do not contribute to apnea-hypopnea index or risk of
      obstructive sleep apnea.

PMID- 21737597
TI  - Confusion of wide thrombolytic time window for acute pulmonary embolism: mass
      spectrographic analysis for thrombus proteins.

PMID- 21737599
TI  - Strain-rate imaging predicts the attenuation of left ventricular remodeling
      induced by ischemic postconditioning after myocardial infarction in mice.
AB  - BACKGROUND: Systolic strain rate (SR) has been shown to correlate with the
      transmural extent of myocardial infarction (MI). Ischemic postconditioning (PC)
      decreases MI size. We aimed to determine whether SR may predict the reduction of
      left ventricular (LV) remodeling induced by PC in a murine model of ischemia
      reperfusion. METHODS AND RESULTS: C57BL6 mice underwent 60 minutes of left
      coronary artery occlusion followed by reperfusion. PC consisted of 3 cycles of 1
      minute of reperfusion and 1 minute of ischemia performed immediately after
      reperfusion. After 24 hours of reperfusion, a first subset of mice was euthanized
      for determination of infarct size. An additional subset of mice underwent 3
      months of reperfusion. Echocardiography and SR were serially assessed at
      baseline, 3 days, and 1, 2, 3 months after reperfusion. PC decreased the infarct
      size and increased SR values within infarcted segments as soon as 24 hours after
      reperfusion as compared with controls (14 +/- 1 versus 6 +/- 1 s(-1), P<0.001).
      Systolic SR was correlated with MI size assessed by the area of infarction/area
      at risk (r=-0.88, P<0.001). At 3 months, PC improved LV ejection fraction (55 +/-
      4 versus 45 +/- 3%; P<0.05) and decreased LV dimensions as compared with
      controls. Strain rate at day 3 correlated with LV ejection fraction (0.75;
      P<0.001), end-systolic (r=-0.75; P=0.001), and end-diastolic volumes (r=-0.70;
      P<0.001) at month 3. CONCLUSIONS: In this murine model of MI, SR accurately
      assessed the reduction in MI size induced by PC early after reperfusion and the
      subsequent reduction of LV remodeling.

PMID- 21737598
TI  - Left atrial size is a potent predictor of mortality in mitral regurgitation due
      to flail leaflets: results from a large international multicenter study.
AB  - BACKGROUND: Left atrium (LA) enlargement is common in organic mitral
      regurgitation (MR) and is an emerging prognostic indicator. However, outcome
      implications of LA enlargement have not been analyzed in the context of routine
      clinical practice and in a multicenter study. METHODS AND RESULTS: The Mitral
      Regurgitation International DAtabase (MIDA) registry enrolls patients with
      organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US
      and European centers. We investigated the relation between LA diameter and
      mortality under medical treatment and after mitral surgery in 788 patients in
      sinus rhythm (64+/-12 years; median LA, 48 [43 to 52] mm). LA diameter was
      independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04
      to 1.12] per 1 mm increment). Compared with patients with LA <55 mm, those with
      LA >=55 mm had lower 8-year overall survival (P<0.001). LA >=55 mm independently
      predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac
      mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The
      association of LA >=55 mm and mortality was consistent in subgroups. Similar
      excess mortality associated with LA >=55 mm was observed in asymptomatic and
      symptomatic patients (P for interaction, 0.77). In patients who underwent mitral
      surgery, LA >=55 mm had no impact on postoperative outcome (P>0.20). Mitral
      surgery was associated with greater survival benefit in patients with LA >=55 mm
      compared with LA <55 mm (P for interaction, 0.008). CONCLUSIONS: In MR caused by
      flail leaflets, LA diameter >=55 mm is associated with increased mortality under
      medical treatment, independent of the presence of symptoms or left ventricular
      dysfunction.

PMID- 21737600
TI  - Integration of 3D imaging data in the assessment of aortic stenosis: impact on
      classification of disease severity.
AB  - BACKGROUND: In patients with aortic stenosis (AS), precise assessment of severity
      is critical for treatment decisions. Estimation of aortic valve area (AVA) with
      transthoracic echocardiographic (TTE)-continuity equation (CE) assumes a circular
      left ventricular outflow tract (LVOT). We evaluated incremental utility of 3D
      multidetector computed tomography (MDCT) over TTE assessment of AS severity.
      METHODS AND RESULTS: We included 51 patients (age, 81+/-8 years; 61% men; mean
      gradient, 42 +/- 12 mm Hg) with calcific AS who underwent evaluation for
      treatment options. TTE parameters included systolic LVOT diameter (D) and
      continuous and pulsed wave (CW and PW) velocity-time integrals (VTI) through the
      LVOT and mean transaortic gradient. MDCT parameters included systolic LVOT area,
      ratio of maximal to minimal LVOT diameter (eccentricity index), and aortic
      planimetry (AVA(p)). TTE-CE AVA [(D(2)*0.786*VTIpw)/VTIcw] and dimensionless
      index (DI) [VTIpw/VTIcw] were calculated. Corrected AVA was calculated by
      substituting MDCT LVOT area into CE. The majority (96%) of patients had eccentric
      LVOT. LVOT area, measured on MDCT, was higher than on TTE (3.84 +/- 0.8 cm(2)
      versus 3.03 +/- 0.5 cm(2), P<0.01). TTE-AVA was smaller than AVA(p) and corrected
      AVA (0.67 +/- 0.1cm(2), 0.82 +/- 0.3 cm(2), and 0.86 +/- 0.3 cm(2), P<0.01).
      Using TTE measurements alone, 73% of patients had congruence for severe AS (DI
      <=0.25 and CE AVA <0.8 cm(2)), which increased to 92% using corrected CE.
      CONCLUSIONS: In patients with suspected severe AS, incorporation of MDCT-LVOT
      area into CE improves congruence for AS severity.

PMID- 21737601
TI  - Evaluation of the left atrial appendage with real-time 3-dimensional
      transesophageal echocardiography: implications for catheter-based left atrial
      appendage closure.
AB  - BACKGROUND: Precise knowledge of left atrial appendage (LAA) orifice size is
      crucial for correct sizing of LAA closure devices. The aim of the present study
      was to determine the performance of real-time 3D transesophageal echocardiography
      (RT3DTEE) for LAA orifice size assessment, compared with 2D transesophageal
      echocardiography (2DTEE), and to investigate the impact of atrial fibrillation
      (AF) on LAA orifice size. METHODS AND RESULTS: One hundred thirty-seven patients
      (38 control subjects, 31 with paroxysmal AF, 38 with persistent AF and 30 with
      permanent AF) underwent 2DTEE and RT3DTEE. Both techniques were used to measure
      LAA orifice area. Clinically-indicated 64-slice computed tomography (CT) was used
      as reference technique in 46 patients. Two-dimensional TEE underestimated LAA
      orifice area, compared with RT3DTEE (1.99+/-0.94 cm(2) versus 3.05+/-1.27 cm(2);
      P<0.001). RT3DTEE showed higher correlation with CT for the assessment of LAA
      orifice area, compared with 2DTEE (r=0.92; 95% confidence interval, 0.85 to 0.95,
      versus r=0.72; 95% confidence interval, 0.54 to 0.83, respectively). At Bland
      Altman analysis, RT3DTEE and 2DTEE underestimated LAA orifice area, compared with
      CT. However, RT3DTEE showed smaller bias (0.07 cm(2) versus 0.72 cm(2)) and
      narrower limits of agreement (-0.71 to 0.85 cm(2) versus -0.58 to 2.02 cm(2))
      with CT, compared with 2DTEE. Among AF patients, a progressive increase in
      RT3DTEE-derived LAA orifice area was observed with increasing frequency of AF
      (P<0.001). At multivariate analysis, AF and left atrial volume index (P<0.001 for
      both) were independently associated with RT3DTEE-derived LAA orifice area.
      CONCLUSIONS: RT3DTEE is more accurate than 2DTEE for the assessment of LAA
      orifice size. A progressive increase in LAA orifice area is observed with
      increasing frequency of AF.

PMID- 21737602
TI  - Fasting-induced myocardial lipid accumulation in long-chain acyl-CoA
      dehydrogenase knockout mice is accompanied by impaired left ventricular function.
AB  - BACKGROUND: Lipotoxicity may be a key contributor to the pathogenesis of cardiac
      abnormalities in mitochondrial long-chain fatty acid beta-oxidation (FAO)
      disorders. Few data are available on myocardial lipid levels and cardiac
      performance in FAO deficiencies. The purpose of this animal study is to assess
      fasting-induced changes in cardiac morphology, function, and triglyceride (TG)
      storage as a consequence of FAO deficiency in a noninvasive fashion. METHODS AND
      RESULTS: MRI and proton magnetic resonance spectroscopy ((1)H-MRS) were applied
      in vivo in long-chain acyl-CoA dehydrogenase (LCAD) knockout (KO) mice and wild
      type (WT) mice (n=8 per genotype). Fasting was used to increase the heart's
      dependency on FAO for maintenance of energy homeostasis. In vivo data were
      complemented with ex vivo measurements of myocardial lipids. Left ventricular
      (LV) mass was higher in LCAD KO mice compared with WT mice (P<0.05), indicating
      LV myocardial hypertrophy. Myocardial TG content was higher in LCAD KO mice at
      baseline (P<0.001) and further increased in fasted LCAD KO mice (P<0.05).
      Concomitantly, LV ejection fraction (P<0.01) and diastolic filling rate (P<0.01)
      decreased after fasting, whereas these functional parameters did not change in
      fasted WT mice. Myocardial ceramide content was higher in fasted LCAD KO mice
      compared with fasted WT mice (P<0.05). CONCLUSIONS: Using a noninvasive approach,
      this study reveals accumulation of myocardial TG in LCAD KO mice. Toxicity of
      accumulating lipid metabolites such as ceramides may be responsible for the
      fasting-induced impairment of cardiac function observed in the LCAD KO mouse.

PMID- 21737603
TI  - Emotional consequences of collective action participation: differentiating self
      directed and outgroup-directed emotions.
AB  - The present research examines the emotional and behavioral consequences of
      collective action participation. It demonstrates that "positive" and "negative"
      emotions can be experienced simultaneously as a result of collective action
      participation, yet it is important to distinguish outgroup-directed from self
      directed emotions. Results of two experiments (N = 71 and N = 101) that
      manipulated participation in collective action illustrate that whereas collective
      action participants experience more outgroup-directed anger and contempt, they
      feel more self-directed positive affect. Furthermore, collective action
      participation predicted willingness to engage in moderate and radical collective
      actions in the future. These relations were mediated by outgroup-directed, but
      not by self-directed, emotions, suggesting that outgroup-directed rather than
      self-directed emotions play a crucial role in the maintenance of protest
      behavior. Theoretical and practical implications of these findings are discussed.

PMID- 21737604
TI  - Thrombopoiesis: new ITP paradigm?

PMID- 21737605
TI  - PET scans: when and how?

PMID- 21737606
TI  - gammadelta cells making IL-17.

PMID- 21737607
TI  - JAKs, Stats, and CK2?

PMID- 21737608
TI  - Marching single file or 2 abreast.

PMID- 21737609
TI  - Synthetic lethality-based targets for discovery of new cancer therapeutics.
AB  - Synthetic lethality is based on the incompatibility of cell survival with the
      loss of function of two or more genes, not with loss of function of a single
      gene. If targets of synthetic lethality are deregulated or mutated in cancer
      cells, the strategy of synthetic lethality can result in significant increase of
      therapeutic efficacy and a favourable therapeutic window. In this review, we
      discuss synthetic lethality based on deficient DNA repair mechanisms, activating
      mutations of RAS, loss of function mutations of the tumor suppressor genes p53,
      Rb and von Hippel-Lindau, and disruption of interactive protein kinase networks
      in the context of development of new anticancer agents.

PMID- 21737610
TI  - Therapy-, gender- and race-specific microRNA markers, target genes and networks
      related to glioblastoma recurrence and survival.
AB  - AIM: To identify and study targets of microRNA biomarkers of glioblastoma
      survival across events (death and recurrence) and phases (life expectancy or post
      diagnostic) using functional and network analyses. MATERIALS AND METHODS:
      microRNAs associated with glioblastoma survival within and across race, gender,
      recurrence, and therapy cohorts were identified using 253 individuals, 534
      microRNAs, Cox survival model, cross-validation, discriminant analyses, and cross
      study comparison. RESULTS: All 45 microRNAs revealed as being associated with
      survival were confirmed in independent cancer studies and 25 in glioblastoma
      studies. Thirty-nine and six microRNAs (including hsa-miR-222) were associated
      with one and multiple glioblastoma survival indicators, respectively. Nineteen
      and 26 microRNAs exhibited cohort-dependent (including hsa-miR-10b with therapy
      and hsa-miR-486 with race) and independent associations with glioblastoma,
      respectively. CONCLUSION: Sensory perception and G protein-coupled receptor
      processes were enriched among microRNA gene targets also associated with survival
      and network visualization highlighted their relations. These findings can help to
      improve prognostic tools and personalized treatments.

PMID- 21737611
TI  - A paradigm shift in EPH receptor interaction: biological relevance of EPHB6
      interaction with EPHA2 and EPHB2 in breast carcinoma cell lines.
AB  - EPH receptors are the largest known family of receptor tyrosine kinases
      characterized in humans. These proteins are involved in axon guidance, tissue
      organization, synaptic plasticity, vascular development and the progression of
      various diseases including cancer. The varied biological effects of EPH receptors
      are mediated in part by the expression of these proteins and their intracellular
      binding proteins. The ability of EPH molecules to form heterodimers within their
      own class has been suggested, although not exhaustively characterized. We have
      clarified this phenomenon by showing that EPHB6, a kinase-deficient receptor, can
      interact with EPHB2 in mammalian cells, and more significantly EPHB6 interacts
      with EPHA2. However, EPHB6 does not interact with another kinase-deficient
      receptor, EPHA10. The interaction between EPHB6 and EPHA2 is the first
      demonstration of an A-type receptor interacting with a B-type receptor.
      Furthermore, we correlated relative expression of EPHB6, EPHB2 and EPHA2 with non
      invasive and invasive phenotypes of breast tumor cell lines. Our results indicate
      that tumor invasiveness-suppressing activity of EPHB6 is mediated by its ability
      to sequester other kinase-sufficient and oncogenic EPH receptors. These
      observations suggest that cellular phenotypes may, in part, be attributed to a
      combinatorial expression of EPH receptors and heteromeric interactions among the
      same class, as well as between two classes, of EPH receptors. Our results also
      suggest that EPHA10 may transduce signals by interacting with other kinase
      sufficient receptors in a similar manner.

PMID- 21737612
TI  - mRNA expression of the putative antimetastatic gene BRMS1 and of apoptosis
      related genes in breast cancer.
AB  - Breast cancer metastasis suppressor-1 (BRMS1) is a putative antimetastatic gene.
      However, results relating its expression to the prognosis of breast cancer are
      still controversial, and all studies carried out to date have failed to show a
      relationship between the expression of BRMS1 and axillary lymph node metastasis
      in breast cancer. It has been recently suggested that BRMS1 may exert its
      physiological role through the modulation of apoptosis. In order to test this
      hypothesis, we studied the expression of BRMS1 and genes known to be directly
      related with apoptosis in human breast carcinoma. The expression of mRNA
      corresponding to BRMS1, BCL2, BAX, CASP3 and the apoptosis-related X-chromosome
      RNA binding motif (RBM) genes (RBMX, RBM3, RBM10 small and large variant) was
      studied by means of differential RT-PCR in 94 samples obtained from previously
      untreated patients with breast carcinoma. A significant (p=0.03) inverse
      correlation between BRMS1 mRNA expression and expression of the mRNA
      corresponding to the large variant of the X-chromosome RBM10 gene was found. The
      degree of direct correlation with another member of the X-chromosome RBM gene
      family, RBMX, almost attained statistical significance (p=0.06). These results
      point towards a possible link between BRMS1 expression and apoptosis in human
      breast cancer through a relationship with the expression of genes belonging to
      the X-chromosome RBM family.

PMID- 21737613
TI  - Gene expression profiling and its utility in prediction of local relapse after
      breast-conserving therapy in early breast cancer.
AB  - BACKGROUND: Local relapse (LR) after breast-conserving therapy (BCT) is not
      accurately predicted by histological/clinical factors. Gene expression profiling
      was used here to discover LR-associated transcriptional alterations. MATERIALS
      AND METHODS: Gene expression profiling was carried out of 81 early breast
      carcinomas obtained from 30 patients who developed a LR (LR(+)) after BCT and 51
      who did not (LR(-)). LR(+) and LR(-) samples were matched for known LR risk
      features. RESULTS: LR was not associated with a given molecular subtype.
      Supervised analysis identified a 212-gene signature, which was not validated in
      independent tumors. No gene set or biological pathway was differentially
      expressed between LR(+) and LR(-) groups. Twelve published prognostic expression
      signatures failed to distinguish these groups of carcinomas. The gene expression
      profiles of 9 cases of LR and the corresponding primary tumors were very similar
      despite the delivery of radiotherapy. CONCLUSION: In this series, the onset of LR
      was not predicted by gene expression alterations.

PMID- 21737614
TI  - Resveratrol, through NF-Y/p53/Sin3/HDAC1 complex phosphorylation, inhibits
      estrogen receptor alpha gene expression via p38MAPK/CK2 signaling in human breast
      cancer cells.
AB  - Agents to counteract acquired resistance to hormonal therapy for breast cancer
      would substantially enhance the long-term benefits of hormonal therapy. In the
      present study, we demonstrate how resveratrol (Res) inhibits human breast cancer
      cell proliferation, including MCF-7 tamoxifen-resistant cells (IC(50) values for
      viability were in the 30-45 MUM range). We show that Res, through p38(MAPK)
      phosphorylation, causes induction of p53, which recruits at the estrogen receptor
      alpha (ERalpha) proximal promoter, leading to an inhibition of ERalpha expression
      in terms of mRNA and protein content. These events appear specifically p53
      dependent, since they are drastically abrogated with p53-targeting siRNA.
      Coimmunoprecipitation assay showed specific interaction between p53, the Sin3A
      corepressor, and histone deacetylase 1 (HDAC1), which was phosphorylated. The
      enhancement of the tripartite complex p53/Sin3A/HDAC1, together with NF-Y on Res
      treatment, was confirmed by chromatin immunoprecipitation analyses, with a
      concomitant release of Sp1 and RNA polymerase II, thereby inhibiting the cell
      transcriptional machinery. The persistence of such effects in MCF-7 tamoxifen
      resistant cells at a higher extent than parental MCF-7 cells addresses how Res
      may be considered a useful pharmacological tool to be exploited in the adjuvant
      settings for treatment of breast cancer developing hormonal resistance.

PMID- 21737615
TI  - Tobacco smoke regulates the expression and activity of microsomal prostaglandin E
      synthase-1: role of prostacyclin and NADPH-oxidase.
AB  - Tobacco smoke (TS) interacts with interleukin-1beta (IL-1beta) to modulate
      generation of reactive oxygen species (ROS) and expression of cyclooxygenase-2.
      We explored molecular mechanisms by which TS/IL-1beta alters expression and
      activity of microsomal-prostaglandin E synthase-1 (mPGES-1) and of prostacyclin
      synthase (PGIS) in mouse cardiac endothelial cells. TS (EC(50) ~5 puffs/L)
      interacting with IL-1beta (2 MUg/L) up-regulates PGE(2) production and mPGES-1
      expression, reaching a plateau at 4-6 h, but down-regulates prostacyclin (PGI(2))
      release by increasing IL-1beta-mediated PGIS tyrosine nitration. Inhibition of
      NADPH-oxidase, achieved pharmacologically and/or by silencing its catalytic
      subunit p47phox, or exogenous PGI(2) (carbaprostacyclin; IC(50) ~5 MUM) prevents
      production of both ROS and PGE(2), and negatively modulates mPGES-1 expression
      induced by TS/IL-1beta. Moreover, inhibiting PGI(2), either using PGIS siRNA
      and/or CAY10441 (EC(50) ~20 nM), a PGI(2) receptor antagonist, increases NADPH
      oxidase activation, mPGES-1 synthesis, and PGE(2) production. Finally, lower
      PGI(2) levels associated with higher PGIS tyrosine nitration, p47phox
      translocation to the membrane (an index of activation of NADPH-oxidase), and
      mPGES-1 expression and activity were detected in cardiovascular tissues of ApoE(
      /-) mice exposed to cigarette smoke compared to control mice. In conclusion,
      cigarette smoke in association with cytokines alters the balance between
      PGI(2)/PGE(2), reducing PGI(2) production and increasing synthesis and activity
      of mPGES-1 via NADPH-oxidase activation, predisposing to development of
      pathological conditions.

PMID- 21737616
TI  - The physiological implication of novel proteins in systemic osmoregulation.
AB  - Maintenance of the osmobalance is important for life. In this process, in which
      brain and kidney act in concert, mammals have to cope with significant deviations
      as drinking water reduces plasma osmolality, whereas salty food increases it. To
      restore homeostasis, specialized nuclei within the hypothalamus play a pivotal
      role in detecting changes in plasma osmolality and initiating appropriate
      responses. These responses are accomplished by either changing the intake of
      water or the excretion of water by the kidney. In the past decade, several novel
      findings have made significant contributions to our insights in the process of
      systemic osmoregulation. Novel proteins have been identified in the brain as well
      as in the kidney that are fulfilling important roles in the process of systemic
      osmoregulation. In this review, recent evidence of the involvement of TRPV
      channels (TRPV1, TRPV2, and TRPV4) and proteins, such as sodium channels NALCN
      and Na(x), in neuronal osmoregulation, as well as; e.g., the purinergic P2Y2
      receptor in renal osmoregulation, are discussed, and integrated with existing
      knowledge of systemic osmoregulation.

PMID- 21737617
TI  - Cytotoxic activity of new acetoxycoumarin derivatives in cancer cell lines.
AB  - BACKGROUND: Coumarin and their derivatives are important and useful compounds
      with diverse pharmacological properties. In the present study, we evaluated the
      in vitro cytotoxic activity of new acetoxycoumarin derivatives: 4-(7-methoxy-4
      methyl-2-oxo-2H-chromen-3-yl)phenyl acetate (1), 4-(1-methyl-3-oxo-3H
      benzo[f]chromen-2-yl)phenyl acetate (2), 4-(6-propionamido-4-methyl-2-oxo-2H
      chromen-3-yl) phenyl acetate (3), 4-(7-acetoxy-2-oxo-4-phenyl-2H-chromen-3
      yl)phenyl acetate (4), 4-(2-oxo-4-phenyl-2H-chromen-3-yl)phenyl acetate (5), 4-(6
      bromo-2-oxo-4-phenyl-2H-chromen-3-yl)phenyl acetate (6), 4-(7-(diethylamino)-4
      methyl-2-oxo-2H-chromen-3-yl)phenyl acetate (7), 4-(6,8-dibromo-4-methyl-2-oxo-2H
      chromen-3-yl)phenyl acetate (8) against A549 human lung cancer, CRL 1548 rat
      liver cancer and CRL 1439 normal rat liver cells. MATERIALS AND METHODS: The
      cytotoxic activity was evaluated by crystal violet dye-binding assay. The effect
      of compounds 5 and 7 on different phases of the cell cycle was determined using
      flow cytometry. RESULTS: In the A549 lung cancer cell line, the 50% lethal dose
      (LD50) values for compounds 1-4, 6 and 8 were found to be >100 MUM while those
      for 5 and 7 were 89.3 and 48.1 MUM, respectively after 48 h treatment. In the CRL
      1548 liver cancer cell line, only compound 7 showed toxicity, with an LD50 of
      45.1 MUM. Compounds 5 and 7 caused different cell phase arrest in lung and liver
      cancer cell lines. CONCLUSION: The results indicate that 4-(7-(diethylamino)-4
      methyl-2-oxo-2H-chromen-3-yl)phenyl acetate (7) had the highest cytotoxic
      activity in all of the examined cell lines.

PMID- 21737618
TI  - Characterization of the effect of in vivo doxorubicin treatment on skeletal
      muscle function in the rat.
AB  - Doxorubicin (DOX)-induced muscle dysfunction may contribute to patient fatigue,
      but the nature of this myotoxicity remains unclear. The purpose of this study was
      to characterize the muscle function dose-response to DOX. A secondary purpose was
      to compare the degree of DOX-induced muscle dysfunction to the observed cardiac
      dysfunction. MATERIALS AND METHODS: Rats received DOX at 10 mg/kg (DOX1), 12.5
      mg/kg (DOX2), or 15 mg/kg (DOX3). Muscle and cardiac function were assessed 5
      days, post injection. RESULTS: Compared to controls, DOX2 and DOX3 soleus and
      DOX3 extensor digitorum longus (EDL) had lower maximal twitch force (p<0.05).
      Soleus fatigue rate was altered by DOX, but EDL fatigue rate was not.
      Additionally, fractional shortening was lower in DOX2 and DOX3 compared to
      controls (p<0.05). CONCLUSION: DOX impaired muscle function in a dose-dependent
      manner. The degree of dysfunction was greater in the soleus and was consistent
      with the observed cardiac dysfunction.

PMID- 21737620
TI  - Overexpression of kappa-actin alters growth properties of hepatoma cells and
      predicts poor postoperative prognosis.
AB  - Since Rho-mediated signaling can regulate liver cancer cell proliferation, amino
      acid sequence changes of its downstream targets, actins, might alter the
      properties of cell growth. Here, we investigated the function of a novel class of
      actins, named kappa-actins, in hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: Alexander cells overexpressing an HCC-derived kappa-actin (Alex-kappa
      cells) were established to study growth property changes. kappa-actin expression
      was also determined in tumor and noncancerous tissues from 72 HCC patients.
      Survival analysis was conducted to evaluate the prognostic predictive value of
      kappa-actin expression. RESULTS: Phylogenetic analysis showed that kappa-actin
      sequences constituted 94.7% and 17.6% of actin transcripts in Alex-kappa and
      naive Alexander cells, respectively. Alex-kappa cells exhibited serum-independent
      cell growth with increased anchorage-independent colony formation and BrdU
      incorporation upon serum deprivation. Cox proportional hazard analysis showed
      that kappa-actin expression in both cancerous and noncancerous tissues predicted
      poorer postoperative disease-free survival (p=0.004). CONCLUSION: Overexpression
      of kappa-actin altered growth properties of hepatoma cells, contributing to poor
      postoperative prognosis.

PMID- 21737619
TI  - LLL12 inhibits endogenous and exogenous interleukin-6-induced STAT3
      phosphorylation in human pancreatic cancer cells.
AB  - Pancreatic cancer is one of the most serious types of cancer, with a five-year
      survival rate at only 6%. There is a critical need to develop more effective
      treatments for pancreatic cancer. Growing evidence shows that chronic
      inflammation plays a crucial role in tumor initiation and progression. Here we
      demonstrated that the endogenous expression of the inflammatory cytokine
      interleukin-6 (IL-6) correlates with signal transducer and activator of
      transcription 3 (STAT3) phosphorylation in human pancreatic cancer cells.
      Inhibition of the endogenous IL-6/STAT3 pathway reduces cell viability. Exogenous
      IL-6 induces STAT3 phosphorylation, but differently induces phosphorylation of
      STAT3 upstream kinases, Janus kinase 1(JAK1), JAK2, and tyrosine kinase 2 (TYK2).
      Interestingly, LLL12, a nonpeptide, cell-permeable small molecule, selectively
      blocked exogenous IL-6-induced STAT3 phosphorylation and nuclear translocation in
      both PANC-1 and ASPC-1 pancreatic cancer cell lines independently of the
      phosphorylation of JAK1, JAK2, and TYK2. These results suggest that the
      inhibition of endogenous and exogenous IL-6-mediated STAT3 signaling may be a
      potential therapeutic approach for pancreatic cancer.

PMID- 21737621
TI  - Predicting response to benzamide riboside chemotherapy in hepatocellular
      carcinoma using apparent diffusion coefficient of water.
AB  - AIM: To monitor the effects of the apoptotic agent benzamide riboside (BR) on
      tumor volume and water apparent diffusion coefficient (ADC) in rat hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Water ADC of the tumors and nearby liver
      tissue was measured using diffusion-weighted 1H MRI (DWI). The two groups of BR
      treated animals, which differed in their sensitivity to the treatment, were
      identified as responsive (RBR) and non-responsive (NRBR). RESULTS: Tumor growth
      in the RBR group was arrested and the mean tumor volume in this group was 1/6th
      and 1/16th compared to that of the NRBR group on days 7 and 14 after treatment,
      respectively. Water ADC of HCC was higher than in nearby normal liver tissue.
      Before BR treatment, the mean water ADC was significantly higher in the RBR group
      compared to the NRBR group. BR therapy did not change the water ADC value
      regardless of tumor sensitivity. CONCLUSION: Although the water ADC did not
      change after chemotherapy by BR, DWI has great potential for detecting and
      predicting response to chemotherapy in HCC.

PMID- 21737622
TI  - Disseminated and circulating tumor cells for monitoring chemotherapy in
      urological tumors.
AB  - This review focused on technical advancements in the detection of CTCs/DTCs in
      urogenital cancer. Most of the established methods of circulating tumor cell
      enrichment use density-gradient centrifugation and immunomagnetic procedures.
      Reverse transcriptase polymerase chain reaction (RT-PCR) is another detection
      technique. Novel methods, the CTC chip and the epithelial immunospot (EPISPOT)
      assay, have already shown promising results. For localized and metastatic
      prostate cancer, significant correlations between CTCs/DTCs and well-established
      indicators of disease activity have been demonstrated. Furthermore, various
      studies support the prognostic relevance of CTCs in metastatic bladder and renal
      cell carcinoma patients. Advanced technologies offer new options for estimating
      the risk of progression after curative-intended surgery and may allow a more
      effective monitoring of disease progression or response to therapy.

PMID- 21737623
TI  - Identification of differentially expressed proteins in tumour necrosis factor
      alpha-resistant and -sensitive rat hepatoma cells.
AB  - BACKGROUND: Our earlier studies reported that ONO-4007, a synthetic lipid A
      analogue with low endotoxic activity, had shown much effect on tumour necrosis
      factor (TNF)-alpha-sensitive rat hepatoma cells, even though it had no effect on
      TNF-alpha-resistant cells. MATERIALS AND METHODS: To find biomarkers which relate
      to the sensitivity of cancer cells to TNF-alpha, proteomic differential display
      analysis for TNF-alpha-resistant cKDH-8/11 and -sensitive KDH-8/YK rat hepatoma
      cell lines was carried out using two-dimensional gel electrophoresis and liquid
      chromatography-tandem mass spectrometry. RESULTS: Two-DE analysis showed 32
      spots, whose expression was different between cKDH-8/11 cells and KDH-8/YK cells.
      Of these, 12 were up-regulated and 20 were down-regulated in cKDH-8/11 cells
      compared to KDH-8/YK cells. The up-regulated proteins include transitional
      endoplasmic reticulum ATPase, 78 kDa glucose-regulated protein (GRP78), heat
      shock cognate 71 kDa protein (HSC71) and protein disulfide-isomerase A6. The down
      regulated proteins included alpha-enolase, aldose reductase, glutathione
      reductase, annexin A1, glutamate dehydrogenase 1 and dihydrolipoyl dehydrogenase.
      CONCLUSION: These findings suggest that these differentially regulated proteins
      could be factors responsible for the resistance of cKDH-8/11 cells to TNF-alpha
      induced cell death.

PMID- 21737624
TI  - The therapeutic effects of R8-liposome-BCG-CWS on BBN-induced rat urinary bladder
      carcinoma.
AB  - BACKGROUND: The present gold standard for bladder cancer is Mycobacterium bovis
      bacillus Calmette-Guerin (BCG) immunotherapy, but serious side-effects are
      common. We previously reported that C3H/HeN mice vaccinated with a mixture of MBT
      2 cells and artificial BCG, octaarginine-modified liposomes incorporating the
      cell wall of BCG (R8-liposome-BCG-CW), significantly inhibited growth of R8
      liposome-BCG-CW pretreated MBT-2 cells. Our aim was to determine if a non-live
      bacterial agent could be as efficacious as live BCG in a model of bladder cancer.
      We investigated the suppressive effect of liposome-incorporating cell wall
      skeleton (BCG-CWS) on N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced
      urinary bladder carcinogenesis in rats. MATERIALS AND METHODS: F344 rats were fed
      with BBN and sodium ascorbate for 8 weeks, after which all rats were confirmed to
      have excreted atypical epithelial cells in the urine. Rats were administered BCG
      CW(1.0 mg/rat) or R8-liposome-BCG-CWS (0.1 or 1.0 mg/rat) intravesically
      once/week for 8 weeks from week 28 to 35 of the experimental protocol. RESULTS:
      Rats receiving R8-liposome-BCG-CWS intravesically showed significantly inhibited
      numbers of tumors, especially those of simple hyperplasia, in comparison with the
      control rats. CONCLUSION: R8-liposome-BCG-CWS administration had inhibitory
      effects on rat bladder carcinogenesis. These results may indicate a novel
      adoptive immunotherapy against bladder cancers.

PMID- 21737625
TI  - Ischemic time impacts biological integrity of phospho-proteins in PI3K/Akt,
      Erk/MAPK, and p38 MAPK signaling networks.
AB  - Post-translational modifications of proteins, such as phosphorylation, are labile
      events dynamically regulated by opposing kinase and phosphatase activities.
      Preanalytical factors, such as ischemic time before fixation, affect these
      activities and can have a significant impact on the ability to elucidate
      signaling pathways in tissue. Immunohistochemical analysis of phosphorylated
      proteins involved in PI3K/Akt, Erk/MAPK, and p38 MAPK signaling networks was
      performed in human cell line xenografts from lung, brain, ovary, and prostate
      tumors. In order to replicate real-world practices, the tissues were subjected to
      ischemic times of 0 (baseline), 1, 4, and 24 hours before fixation in formalin.
      Two key concepts emerge from this analysis: (1) the stability of different
      phospho-epitopes within a given tumor type is variable (e.g. phospho-PRAS40 is
      more labile than phospho-S6 ribosomal protein) and (2) the stability of a given
      phospho-epitope (e.g. phospho-MAPKAPK2) varies significantly across different
      tumor types. These results highlight the importance of proper tissue acquisition
      and rapid fixation to preserve the biological integrity of signal transduction
      pathways that may guide therapeutic decision making.

PMID- 21737626
TI  - Bioactivity of synthetic 2-halo-3-aryl-4(3H)-quinazoliniminium halides in L1210
      leukemia and SK-BR-3 mammary tumor cells in vitro.
AB  - BACKGROUND: Because quinazolines and their derivatives exhibit a wide range of
      pharmacological profiles, there is a continuous interest among synthetic and
      medicinal chemists in the discovery of more potent analogs. Ten novel
      quinazoliniminium salts were synthesized and tested for their effectiveness
      against murine and human tumor cell proliferation in vitro. MATERIALS AND
      METHODS: Various markers of tumor cell metabolism, DNA degradation and mitotic
      disruption were assayed in vitro to evaluate drug cytotoxicity. RESULTS: All
      compounds induced concentration- and time-dependent antitumor effects in vitro
      but the 2-chloro-3-(4-methoxyphenyl)quinazolin-4(3H)-iminium chloride (4) was the
      most effective inhibitor of leukemia L1210 cell proliferation at days 2-4 (IC50:
      2.1-0.9 MUM), suggesting that the para-methoxyphenyl substituent on the N3 of 4
      may enhance the antiproliferative properties of the quinazoliniminium scaffold.
      In mammary SK-BR-3 tumor cells, 4 reduced the Ki-67 marker of cell proliferation
      at 24 h and the metabolic activity at days 2 and 4. Moreover, a 1.5- or 3-h
      treatment with 4 was sufficient to inhibit the rates of DNA, RNA and protein
      syntheses measured in L1210 cells over 0.5- or 1-h periods of pulse-labeling with
      3H-thymidine, 3H-uridine and 3H-leucine, respectively. As 4 did not reduce the
      fluorescence of the ethidium bromide-DNA complex, this compound was unlikely to
      directly bind to or destabilize double-stranded DNA. However, 4 induced DNA
      cleavage at 24 h in L1210 cells containing 3H-thymidine-prelabeled DNA,
      suggesting that this antitumor drug might trigger an apoptotic pathway of DNA
      fragmentation. After 12-48 h, 4 weakly increased the mitotic index of L1210 cells
      but stimulated the formation of many binucleated cells, multinucleated cells and
      micronuclei, suggesting that this antitumor compound might enhance mitotic
      abnormality, induce chromosomal damage or missegregation, and block cytokinesis.
      CONCLUSION: Although 4 may have interesting bioactivity, more compounds based on
      the quinazoliniminium scaffold must be synthesized to elucidate structure
      activity relationships, identify more potent antitumor lead compounds, and
      investigate their molecular targets and mechanisms of action.

PMID- 21737627
TI  - Associations of HSP90 client proteins in human breast cancer.
AB  - BACKGROUND: HSP90 has been studied intensively as a therapeutic target, however
      little is known regarding specific interactions of the large number of HSP90
      client proteins. Therefore, this study investigated HSP90 client proteins
      sensitive to the HSP90 inhibitor geldanamycin in tumour and healthy breast
      tissue. MATERIALS AND METHODS: Co-immunoprecipitation and SDS-PAGE were used to
      investigate protein interactions. Western blotting and LC-MS were used to infer
      protein identities. RESULTS: HSP90 client proteins were observed in 7 out of 11
      breast cancer patients. Further experiments inferred HSP40, -56/FKBP52, -60, -70,
      -105 and lumican to associate with HSP90 and to belong to this group of
      geldanamycin-sensitive proteins. In one patient, a cancer-specific group of
      proteins was identified. In all experiments geldanamycin resistance was observed.
      CONCLUSION: HSP90 differentially associated with client proteins and this was
      patient dependent. Geldanamycin resistance and lack of HSP90 client protein
      expression may limit clinical applications of HSP90 inhibitors.

PMID- 21737628
TI  - Proteomic differential display analysis for TS-1-resistant and -sensitive
      pancreatic cancer cells using two-dimensional gel electrophoresis and mass
      spectrometry.
AB  - TS-1 is an oral anticancer agent containing two biochemical modulators for 5
      fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU.
      TS-1 has been recognized as an effective anticancer drug using standard therapies
      for patients with advanced pancreatic cancer along with gemcitabine. However, a
      high level of inherent and acquired tumor resistance to TS-1 induces difficulty
      in the treatment. To identify proteins linked to the TS-1-resistance of
      pancreatic cancer, we profiled protein expression levels in samples of TS-1
      resistant and -sensitive pancreatic cancer cell lines by using two-dimensional
      gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC
      MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP)
      combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc
      1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP
      combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive
      (TS-1-resistant). Proteomic analysis showed that eleven spots, including T
      complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1
      delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down
      regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C,
      endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant
      cells compared with -sensitive cells. These results suggest that the identified
      proteins showing different expression between TS-1-sensitive and -resistant
      pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could
      be useful to overcome the TS-1-resistance of pancreatic cancer cells.

PMID- 21737629
TI  - Response of thyroglobulin to radioiodine therapy in thyroglobulin-elevated
      negative iodine scintigraphy (TENIS) syndrome.
AB  - BACKGROUND: While radioiodine (131-I) is widely used in the treatment of
      differentiated thyroid cancer, its role remains less certain when abnormal 131-I
      uptake cannot be demonstrated in a pre-therapy diagnostic scan. Documentation of
      abnormal 131-I uptake in a post-therapy scan in such cases helps to justify the
      radioiodine therapy, but the post-therapy scan can remain persistently negative.
      AIM: To evaluate (i) whether 131-I therapy had any measurable effect on
      thyroglobulin (Tg) levels in patients who were scan negative prior to radioiodine
      therapy and remained scan negative after therapy, and (ii) whether the magnitude
      of the effect on Tg depended on the pre-therapy Tg level. PATIENTS AND METHODS:
      Retrospective analysis of 78 patients. All patients had pre-therapy and post
      therapy Tg levels measured under stimulation with thyroid stimulating hormone.
      Hospital data until date of last contact were analyzed to assess for recurrent
      disease. RESULTS: Tg levels decreased by 55% in those having Tg 10 MUg/l or
      higher; and by 41% in those with less than 10 MUg/l. In patients with detectable
      Tg antibodies, there were no statistically significant decreases demonstrated for
      either Tg or Tg antibody levels. CONCLUSION: Radioiodine therapy can reduce Tg
      levels, independently of the pre-therapy level, even when the pre-therapy level
      is low and the pre-therapy, as well as the post-therapy, radioiodine scan remains
      negative.

PMID- 21737630
TI  - Dosimetry of a 238Pu-based alpha-particle irradiator and its biological
      application in a study of the bystander effect.
AB  - A better understanding of the non-targeted (bystander) effects of radiation may
      have important implications with regards to radiation risk assessment, radiation
      protection, and targeted cancer therapy. In the present study, the direct and
      bystander effects of alpha-particle irradiation in immortalized human fibroblasts
      (F11hTERT) and breast cancer cells (MCF-7) was investigated. To ensure a more
      accurate dose delivery to these different cell lines, an existing 238Pu alpha
      particle irradiator was improved by the addition of a collimator and the
      development of an analytical equation for calculation of the radiation dose to
      cells. The mean dose rate and alpha-particle fluence were calculated for each
      cell line by taking into consideration the size of their nuclei. Bystander effect
      experiments were performed by transferring medium from irradiated to unirradiated
      cells and by measuring micronucleus formation in the cells. Both the immortalized
      human fibroblasts and the breast cancer cells displayed a bystander effect. In
      conclusion, the broad-beam alpha-particle irradiator improved in this study
      represents a useful tool in the investigation of direct and non-targeted effects
      of alpha-particle radiation.

PMID- 21737631
TI  - P-glycoprotein modulation by valspodar and cyclosporin does not increase tumor
      uptake of doxorubicin administered via isolated lung perfusion to rats bearing
      sarcoma lung metastases.
AB  - BACKGROUND: Isolated lung perfusion (ILP) with doxorubicin allows a regional
      increase in drug exposure while sparing unaffected tissues, but clinical results
      have so far been disappointing, presumably in part because of the limited tumor
      penetration of doxorubicin. The aim of this study was to assess whether tumor
      uptake of doxorubicin, administered locoregionally by ILP, would be increased by
      the administration of P-glycoprotein (P-gp) modulators. MATERIALS AND METHODS:
      Single-pass antegrade ILP (A-ILP) was performed with doxorubicin in rats bearing
      a pulmonary sarcoma nodule which were either untreated or received P-gp
      inhibitors cyclosporin, valspodar or the vehicle, Cremophor(r), only. Doxorubicin
      concentrations in tumor, lung and effluent were measured by high performance
      liquid chromatography (HPLC) coupled to spectrofluorimetric detection and the
      expression of P-gp was examined by Western blot in tumors and lungs. RESULTS:
      Doxorubicin concentrations in tumors were 5- to 10-fold lower than those measured
      in lungs tissues. Doxorubicin penetration in tumors, expressed as tumor retention
      ratios (TR60min), were not different between the groups. Western blot analysis
      did not show any evidence of baseline or doxorubicin-induced P-gp expression in
      the tumor model. CONCLUSION: P-gp modulation with cyclosporin or valspodar fails
      to increase the tumor uptake of doxorubin administered by A-ILP. Other reasons
      for low doxorubicin penetration in tumor, such as high interstitial fluid
      pressure or tumor vasculature barrier, or alternate cell membrane drug
      transporters, need to be examined for a better understanding of impaired
      doxorubicin delivery to tumor.

PMID- 21737632
TI  - Cyclosporine A induces apoptosis of human lung adenocarcinoma cells via caspase
      dependent pathway.
AB  - BACKGROUND: Aerosolized cyclosporine A (CsA) increases the local concentration of
      CsA in lung tissue and has proven to be an effective therapy for refractory
      rejection in lung transplant patients. However, the safety of high concentrations
      of CsA on tumour progression remains controversial. MATERIALS AND METHODS: Human
      lung adenocarcinoma A549 cells were cultured with or without 1-3 MUg/ml of CsA.
      The percentage of apoptotic cells was evaluated by Annexin V staining. The
      expressions of caspase-3, -9, -8 and cytochrome c were determined by Western
      blotting. RESULTS: CsA therapy suppressed the growth of human lung cancer cells
      and increased the percentage of apoptotic cells compared with control cells.
      Western blot analysis revealed that CsA increased the levels of cytosolic
      cytochrome c and cleaved caspase-3 and -9, but not of cleaved caspase-8 in the
      lung cancer cells, suggesting that CsA-induced apoptosis is associated with the
      activation of caspase-3 and -9. CONCLUSION: Our findings indicate that a high
      concentration of CsA has cytocidal effects through the caspase-3- and -9
      dependent apoptotic pathway. This result shows that local administration of CsA
      does not increase the risk of secondary lung cancer.

PMID- 21737633
TI  - Quantitative analysis of thymidine kinase 1 and 5'(3')-deoxyribonucleotidase mRNA
      expression: the role of fluorothymidine uptake.
AB  - BACKGROUND: Thymidine kinase 1 (TK1) and 5'(3')-deoxyribonucleotidase (dNT1)
      regulate the metabolism of thymidine and its analogs. However, the expression
      patterns and roles of these enzymes in fluorothymidine (FLT) uptake have not been
      systemically studied. MATERIALS AND METHODS: TK1 and dNT1 mRNAs were determined
      by quantitative PCR in 20 asynchronously growing lung and colon cancer cell
      lines. [3H]FLT uptake and doubling time were measured. RESULTS: The TK1/GAPDH
      values varied from 3.09*10(-3)+/-6.62*10(-4) to 2.44*10(-2)+/-8.49*10(-4) and
      dNT1/GAPDH values from 5.84*10(-4)+/-4.88*10(-5) to 1.59*10(-2)+/-1.20*10(-3).
      The correlation coefficient of TK1/GAPDH versus dNT1/GAPDH was 0.669 (p<0.001).
      [3H]FLT uptake showed negative moderate correlation with dNT1/GAPDH levels (r=
      0.563; p<0.01), but no significance with TK1/GAPDH levels. Doubling time had no
      relationship with the TK1 or dNT1 expression. CONCLUSION: This study profiled
      correlative expression of TK1 and dNT1 in cancer cell lines, and showed that dNT1
      expression determines the lower uptake of FLT, providing a basis for
      understanding deoxyribonucleotide metabolism.

PMID- 21737634
TI  - Huachansu, containing cardiac glycosides, enhances radiosensitivity of human lung
      cancer cells.
AB  - AIM: To assess radiosensitzing potential of huachansu (HCS) and delineate the
      underlying mechanisms. MATERIALS AND METHODS: Lung cancer cell lines were exposed
      to HCS, radiation or both and subjected to survival assays, Western blots,
      apoptosis assay and immunocytochemical analysis. RESULTS: HCS suppressed the
      viability of all three lung lines tested and enhanced radiosensitivity of H460
      and A549 (wild-type p53) only with no effect on H1299 (p53 null) cells. HCS
      prolonged the presence of radiation-induced gammaH2AX foci and increased
      radiation-induced apoptosis. Western blots showed that HCS increased cleaved
      caspase-3 and cleaved poly-(ADP-ribose) polymerase (PARP) levels, as well as
      reducing BCL-2 and p53 protein levels in H460 cells. CONCLUSION: HCS-enhanced
      radiosensitivity of human lung cancer lines appeared to be p53-dependent.
      Inhibition of DNA repair and increase in radiation-induced apoptosis may have
      served as underlying mechanisms. These data suggest that HCS may have potential
      to improve the efficacy of radiotherapy.

PMID- 21737635
TI  - Estimating preclinical efficacy targets utilizing cetuximab efficacy in KRAS
      mutant and wild-type colorectal cancer models.
AB  - BACKGROUND: Clinically relevant targets for developmental drug efficacy in animal
      models of cancer are critical yet understudied parameters. MATERIALS AND METHODS:
      Cetuximab, a chimeric antibody to epidermal growth factor receptor (EGFR), was
      administered to athymic mice bearing subcutaneous tumors established with 13
      human colorectal cancer cell lines of varying biomarker status, defined by DNA
      sequencing and RT-PCR. RESULTS: If tumor growth inhibition is taken as a target,
      as is commonly done, then in contrast to the clinical situation where KRAS
      mutation strongly predicts for a lack of clinically meaningful benefit in
      colorectal cancer patients, cetuximab alone and in combination with irinotecan
      based chemotherapy were efficacious in a similar proportion of KRAS wild-type and
      mutant models. It was only when tumor regression was utilized to define relevant
      efficacy that cetuximab monotherapy was efficacious in KRAS wild-type, but not
      mutant models. Adding cytotoxic therapy to cetuximab treatment increased tumor
      regression frequency in both genotypes to the point that once again the response
      was similar for KRAS wild-type and mutant models. CONCLUSION: Our data support
      shifting the threshold for claiming clinically relevant targeted therapy efficacy
      in subcutaneous xenograft models towards tumor regression, rather than tumor
      growth inhibition, focusing on the evaluation of tumor cells that are addicted to
      the pathways being targeted.

PMID- 21737636
TI  - Development of glioblastoma cell lines expressing red fluorescence for non
      invasive live imaging of intracranial tumors.
AB  - Glioblastoma (GBM) cell lines expressing red fluorescent proteins were evaluated
      as a tool for non-invasive imaging of orthotopic tumors. MATERIALS AND METHODS:
      mKate2- and mCherry-transduced U251MG GBM lines were sorted by flow cytometry.
      The growth rates and drug sensitivity of the resulting cell lines were compared
      to those of the parental line. Following orthotopic implantation, mKate2
      expressing cells were detected using multispectral imaging. RESULTS: Flow
      cytometry-sorted fluorescent populations exhibiting growth curves that were
      comparable to those of the parental line were selected. mKate2-expressing cells
      were inoculated orthotopically and formed tumors which were visualized non
      invasively, allowing monitoring of tumor growth over time and the assessment of
      tumor response to temozolomide drug treatment. CONCLUSION: The strategy reported
      here led to the successful development of GBM models expressing mKate2 or
      mCherry. The fluorescence signal intensity measured in the brain of live animals
      correlates with tumor size, thus providing a method to assess tumor progression
      and response to treatment.

PMID- 21737637
TI  - Inhibition of expression of HTLV-1 structural genes mediated by short hairpin RNA
      in vitro.
AB  - BACKGROUND: Human T-lymphotropic virus I (HTLV-1) is associated with the T-cell
      malignancy known as adult T-cell leukemia/ lymphoma (ATLL) and with a disorder
      called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
      Currently, the treatment of these diseases is based on symptom relief. RNA
      interference (RNAi) technology has been described as an efficient mechanism for
      development of new therapeutic methods. Thus, the aim of this study was to
      evaluate the inhibition of HTLV-1 structural proteins using short hairpin RNAs
      (shRNAs) expressed by non-viral vectors. MATERIALS AND METHODS: Reporter plasmids
      that express enhanced green fluorescent protein-Gag (EGFP-Gag) and EGFP-Env
      fusion proteins and vectors that express shRNAs corresponding to the HTLV-1 gag
      and env genes were constructed. shRNA vectors and reporter plasmids were
      simultaneously transfected into HEK 293 cells. RESULTS: Fluorescence microscopy,
      flow cytometry and real-time PCR showed that shRNAs were effective in inhibiting
      the fusion proteins. CONCLUSION: These shRNAs are effective against the
      expression of structural genes and may provide an approach to the development of
      new therapeutic agents.

PMID- 21737638
TI  - 3-Oxoolean-12-en-27-oic acid inhibits the proliferation of non-small cell lung
      carcinoma cells by inducing cell-cycle arrest at G0/G1 phase.
AB  - BACKGROUND: Inhibition of cell-cycle progression is a target for the treatment of
      cancer. 3-Oxoolean-12-en-27-oic acid (3-OOLA) has shown significant anticancer
      activity towards diverse cancer cells, but has not been investigated for non
      small cell lung carcinoma (NSCLC) cells. In this study, we investigated the
      antiproliferative effect of 3-OOLA in NSCLC cell lines and its underlying
      mechanism. MATERIALS AND METHODS: The MTT assay, bromodeoxyuridine (BrdU)
      incorporation assay, and flow cytometry were used for cell proliferation studies,
      and annexin V staining for apoptotic effects. Western blot analysis was used to
      evaluate expression of cell-cycle regulatory proteins, such as cyclins and cyclin
      dependent kinases (CDKs). RESULTS: 3-OOLA caused G0/G1 phase cell-cycle arrest
      without inducing apoptosis in NSCLC cells, and Western blot analyses demonstrated
      down-regulation of cyclin D1, cyclin E and phosphorylated Rb. CONCLUSION: 3-OOLA
      inhibits cell proliferation of NSCLC cells by inducing cell-cycle arrest at G0/G1
      through down-regulation of cyclin D1 and cyclin E.

PMID- 21737639
TI  - Mucous gland metaplasia in the esophagus and gastric mucosa in baboons.
AB  - BACKGROUND: Chewing of regurgitated food elicits in baboons life-long gastro
      esophageal reflux (GER). The acid reflux transforms the multilayered squamous
      cell epithelium of the esophagus into columnar-lined mucosa with mucus-producing
      accessory glands. The function of this mucous gland metaplasia (MGM), which
      mimics Barrett's mucosa with MGM in humans, is to buffer the gastric acid
      entering the esophagus during regurgitation. In a previous study of entire
      esophagi, the majority of baboons showed MGM. The gastric mucosa was not
      investigated. MATERIALS AND METHODS: Hematoxylin-eosin-stained sections from the
      esophagus, from the lesser gastric curvature and from the greater gastric
      curvature were collected separately from 50 adult baboons. The presence of MGM
      was assessed in each one of these locations. RESULTS: MGM was demonstrated in 92%
      (46/50) of blocks from the esophagus, in 98% (49/50) of blocks from the lesser
      curvature and in 90% (45/50) of those of the greater curvature (fundus).
      CONCLUSION: The majority of the animals had MGM, not only in the esophagus but
      also in the proximal gastric mucosa. Rationally, MGM in baboons starts in the
      distal esophagus and proceeds downwards, towards the proximal stomach. The
      histogenesis of the MGM in Barrett's mucosa in humans (that is Barrett's mucosa
      type 2) remains elusive. Therefore the baboon might be an important animal model
      for studying the histogenesis of Barrett's mucosa with MGM in humans, a
      recognized pre-cancerous lesion.

PMID- 21737640
TI  - Correlation between COX-2 and APC expression in left versus right-sided human
      colon cancer.
AB  - BACKGROUND: Because of clinicopathologic and genetic differences between left
      sided colorectal cancer (LSCRC) and right-sided colon cancer (RSCC),
      cyclooxygenase-2(COX-2) and adenomatous polyposis coli (APC) expression may be of
      clinical relevance. MATERIALS AND METHODS: Clinicopathologic information for 72
      primary colon tumors, 44 left and 28 right, from 72 patients (34 F, 38 M) were
      analyzed. COX-2 and wild-type APC (W-APC) immunohistochemical expressions were
      determined for each case. The data were analyzed using the Chi-square test and
      exact binomial confidence intervals. RESULTS: Overall, 31 out of 44 (70%) LSCRC
      were W-COX-2 positive vs. 13 out of 28 (46%) RSCC (p-value=0.042). When evaluated
      independently of the anatomic location, COX-2 expression showed a borderline
      statistical correlation with the lack of W-APC protein (p-value=0.054). When
      considering location of tumors, the inverse correlation between COX-2 and W-APC
      expression became statistically significant (p-value=0.024). CONCLUSION: We
      report a strong inverse correlation between COX-2 and W-APC expression, with COX
      2 being more frequently as expressed in LSCRC. These data may be useful to
      stratify colorectal cancer patients into right- and left-sided and COX-2
      expressor and non-expressor subsets, when evaluating COX-2 inhibitor and other
      targeted therapies in colon cancer.

PMID- 21737641
TI  - Circulating 20S proteasome in patients with non-metastasized breast cancer.
AB  - BACKGROUND: Recent data suggest a role of the ubiquitin-proteasome system in
      various malignancies. In patients with neoplasms, increased extracellular
      concentrations of circulating 20S proteasome (c-proteasome) have been detected in
      blood plasma. We tested the hypothesis that the plasma c-proteasome concentration
      is a biomarker associated with tumor stage and nodal status in patients with the
      primary diagnosis of non-metastatic breast cancer. PATIENTS AND METHODS: Venous
      plasma concentration of 20S proteasome was measured by ELISA technique in 224 non
      metastatic breast cancer patients and in 50 healthy volunteers. To assess the
      relation of proteasome expression to c-proteasome concentration, tumor specimens
      from 32 patients were immunohistochemically stained for 20S proteasome using an
      antibody directed against the core subunits of the catalytic domain of the 20S
      proteasome. RESULTS: The median c-proteasome concentration was higher (p<0.0001)
      in breast cancer patients (397.5 ng/ml, range: 200-50,000 ng/ml) than in healthy
      controls (305 ng/ml, range: 140-425 ng/ml). There was no significant correlation
      between c-proteasome concentration and strength of proteasomal staining in tumor
      specimens. Neither tumor size, nor nodal status, nor any other prognostically
      important clinical parameter, including the presence of disseminated tumor cells
      in the bone marrow, correlated with high c-proteasome concentrations. CONCLUSION:
      Circulating proteasome concentrations appear to be higher in patients presenting
      with primary breast cancer than in healthy controls. Thus, the ubiquitin
      proteasome system might represent a potential target in breast cancer treatment.

PMID- 21737642
TI  - Etomidate induces cytotoxic effects and gene expression in a murine leukemia
      macrophage cell line (RAW264.7).
AB  - Etomidate is an important tool in the arsenal of the emergency physician, and it
      has been used in a variety of scenarios for both intubation and procedural
      sedation. In the present study, we investigated the cytotoxicity of etomidate
      including induction of apoptosis, and levels of protein and gene expressions
      associated with apoptotic cell death in murine leukemia RAW264.7 cells in vitro.
      Cytotoxic and apoptotic responses to etomidate of RAW264.7 cells, including cell
      morphological changes and cell viability were examined and measured by phase
      contrast microscopy and flow cytometric assay, respectively. Results indicated
      that etomidate increased apoptotic cell morphological changes and reduced cell
      viability in RAW264.7 cells. 4',6-Diamidino-2-phenylindole (DAPI) staining also
      showed that etomidate induced the formation of apoptotic bodies, a characteristic
      of apoptosis. Results from Western blotting indicated that etomidate enhanced the
      levels of cytochrome c, apoptosis-inducing factor (AIF), endonuclease G (Endo G),
      caspase-9, caspase-3 active form and Bax proteins, but it inhibited the
      expression of Bcl-xl, leading to apoptosis. DNA microarray assay indicated that
      etomidate increased the expression of 17 genes (LOC676175; Gm14636;
      2810021G02Rik; Iltifb; Olfr1167; Ttc30b; Olfr766; Gas5; Rgs1; LOC280487; V1rd4;
      Hist1h2bc; V1rj3; Gm10366; Olfr192; Gm10002 and Cspp1) and reduced the expression
      of 15 genes: (Gm10152; Gm5334; Olfr216; Lcn9; Gm10683; Gm5100; Tdgf1; Cypt2;
      Gm5595; 1700018F24Rik; Gm10417; Maml2; Olfr591; Trdn and Apol7c). In conclusion,
      etomidate induced cytotoxic and apoptotic effects the in murine leukemia RAW264.7
      cells in vitro.

PMID- 21737643
TI  - 18beta-glycyrrhetinic acid and glabridin prevent oxidative DNA fragmentation in
      UVB-irradiated human keratinocyte cultures.
AB  - BACKGROUND: UVB radiation is the major etiological factor in the pathogenesis of
      skin aging and cancer development. New approaches to prevent and reverse UVB
      damage are needed to reduce sunlight-induced skin cancer. This study aimed to
      investigate a possible protective activity of liquorice root extracts
      glycyrrhizin (GL), 18beta-glycyrrhetinic acid (18beta-GA) and glabridin (GLB)
      against UVB radiation damage in human keratinocyte cultures. MATERIALS AND
      METHODS: The MTT test was performed to assess cell viability. DNA damage was
      evaluated by comet assay, whereas generation of intracellular reactive oxygen
      species (ROS) was measured by fluorescent 2'7'-dichlorodihydrofluorescein
      diacetate assay. In addition, the activation of p53, regulation of BCL-2 and PARP
      cleavage were analyzed by Western blot analysis. RESULTS: The treatment of human
      keratinocytes with 18beta-GA and GLB prevented direct and indirect DNA damage
      avoiding apoptosis activation. CONCLUSION: 18beta-glycyrrhetinic acid and
      glabridin are potent antioxidants that prevent oxidative DNA fragmentation and
      the activation of apoptosis-associated proteins in human keratinocytes.

PMID- 21737644
TI  - NK4 gene expression enhances 5-fluorouracil-induced apoptosis of murine colon
      cancer cells.
AB  - BACKGROUND: The hepatocyte growth factor (HGF)-Met pathway plays a role in
      progression to malignant characteristics in tumors, including that of resistance
      to anticancer drugs. The purpose of this study was to elucidate the possibility
      of the combination therapy of NK4, a competitive antagonist for HGF. MATERIALS
      AND METHODS: We established a genetically modified murine colon cancer cell,
      CT26, to produce abundant NK4 (CT26/NK4). Cell proliferation, apoptosis, cell
      cycle, intracellular signaling, and 5-fluorouracil (5-FU) metabolism of this cell
      line were examined. RESULTS: There was no difference in thymidylate synthase mRNA
      level between mock-transfected control CT26 cells and CT26/NK4 cells, suggesting
      that NK4 expression does not change 5-FU metabolism. NK4 gene expression enhanced
      5-FU-induced caspase-3 and -7 activation of CT26. Cell cycle analysis showed that
      NK4 gene expression and 5-FU treatment caused an increase in the proportion of
      sub-G(1) cells. On 5-FU treatment, phosphorylation of Akt and Erk1/2 was
      suppressed in CT26/NK4 less than in mock-transfected cells. 5-FU showed a
      stronger cytotoxic activity towards CT26/NK4 cells than control CT26 cells.
      CONCLUSION: 5-FU exerts an additional effect on apoptosis of NK4-expressing CT26
      cells by down-regulating intracellular signaling of the HGF/c-Met pathway.

PMID- 21737645
TI  - Paraoxonase-1 192/55 polymorphisms and the risk of lung cancer in a Turkish
      population.
AB  - AIM: The purpose of the present study was to investigate the possible association
      of paraoxonase-1 (PON1) 192/55 polymorphisms with lung cancer (LC) risk in a
      Turkish population. MATERIALS AND METHODS: A population-based, case-control study
      was carried out, including 223 patients with LC and 234 controls. The frequencies
      of PON1 192/55 genotypes were compared in patient and control groups using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. RESULTS: Distribution of PON1 192 R (+) genotype was found to be
      significantly higher in patients with LC compared to the controls (odds ratio:
      1.497, 95% confidence interval: 1.034-2.166). This difference was especially
      noteworthy in patients with small cell carcinoma and squamous cell carcinoma.
      CONCLUSION: This is the first case-control study on the association between PON1
      polymorphisms and LC susceptibility in a Turkish population. Our results suggest
      that PON1 192 polymorphsim is associated with an increased risk of LC in the
      Turkish population and may be a useful genetic marker for small cell and squamous
      cell carcinoma.

PMID- 21737646
TI  - Combined valproic acid and celecoxib treatment induced synergistic cytotoxicity
      and apoptosis in neuroblastoma cells.
AB  - BACKGROUND: The effects of combined valproic acid (VPA) and celecoxib treatment
      on cancer cells have not been reported. In this study, we examined the effects of
      VPA and celecoxib, alone and combined, on human SH-SY5Y neuroblastoma cells.
      MATERIALS AND METHODS: The cytotoxicity effects of VPA, celecoxib, and combined
      VPA and celecoxib treatment on neuroblastoma cells were studied. The apoptotic
      fraction and the cell cycle distribution of neuroblastoma cells were analyzed by
      flow-activated cell sorter analysis. Western blot analysis was used to
      investigate the expression of cyclooxygenase-2, p53, 14-3-3sigma, p21, p27, Bcl-2
      and Bax in neuroblastoma cells treated with various regimens. RESULTS: Combined
      VPA and celecoxib treatment caused more cytotoxicity and apoptosis in
      neuroblastoma cells than individual drug treatment (p<0.05). In addition,
      combination treatment caused more neuroblastoma cells to accumulate in the G0/G1
      phase of the cell cycle (p<0.04) and induced higher p21 and p27 expression than
      individual drug treatment or control. CONCLUSION: Combined VPA and celecoxib
      treatment induced more cytotoxicity and apoptosis in neuroblastoma cells than
      individual drug treatment. The effects were probably related to the increased p21
      and p27 expression, and G0/G1 accumulation of neuroblastoma cells.

PMID- 21737647
TI  - Selective inhibition of HTLV-1-infected cell proliferation by a novel
      tetramethylnaphthalene derivative.
AB  - Adult T-cell leukemia (ATL) is caused by infection with human T-lymphotropic
      virus type 1 (HTLV-1). A novel tetramethylnaphthalene derivative, TMNAA,
      selectively inhibited the proliferation of various HTLV-1-infected cells,
      including ATL cell lines and peripheral blood mononuclear cells (PBMCs) from ATL
      patients. In contrast, the proliferation of uninfected cell lines and PBMCs from
      healthy donors was hardly affected by the compound. Cell-cycle analysis revealed
      that TMNAA increased the population of the G0/G1 phase and reduced that of the S
      phase in HTLV-1-infected cells. TMNAA was found to suppress the phosphorylation
      of retinoblastoma protein and the expression of cyclin-dependent kinase 4 in HTLV
      1-infected cells. Furthermore, the inhibition of cell proliferation was partially
      annihilated by removing the compound. These results indicate that TMNAA exerts
      selective inhibition of HTLV-1-infected cells through a novel mechanism,
      presumably modulating cell cycle regulatory proteins associated with the G0/G1
      phase.

PMID- 21737648
TI  - Down-regulation of EGFL8: a novel prognostic biomarker for patients with
      colorectal cancer.
AB  - BACKGROUND: In a previous study, we reported a critical role of epidermal growth
      factor-like domain 7 (EGFL7) in the metastasis of hepatocellular carcinoma (HCC)
      and documented it to be a prognostic biomarker as well as a potential therapeutic
      target for HCC. However, the role of EGFL8, the only known paralog of EGFL7, in
      human malignancies is currently unclear. PATIENTS AND METHODS: EGFL8 expression
      in 101 cases of colorectal cancer (CRC) patients was determined by quantitative
      reverse transcription-polymerase chain reaction and the clinicopathological
      features of the CRC patients were correlated with the EGFL8 down-regulation
      scores. In addition, the survival curve and Cox regression model were also
      employed to assess the prognostic value of EGFL8 down-regulation. RESULTS: EGFL8
      was significantly decreased in CRC tissues (p<0.0001) and the down-regulation of
      EGFL8 was evidenced in 74.3% (75/101) of the CRC patients. EGFL8 down-regulation
      correlated significantly to distant metastasis (p=0.038) and high TNM stage
      (p=0.012) of CRC. The CRC patients with high EGFL8 down-regulation showed either
      poorer disease-free survival (p=0.0167) or poorer overall survival (p=0.0310)
      than those with low EGFL8 down-regulation. Multivariable analysis identified
      EGFL8 down-regulation as an independent prognostic factor for CRC patients
      (hazard ratio, 12.974; p=0.037). CONCLUSION: The reduced expression of EGFL8 is
      closely related to metastastic potential and poor prognosis of CRC, suggesting
      the down-regulation of EGFL8 as a novel prognostic biomarker for CRC patients.

PMID- 21737649
TI  - Phosphorylation of p53 modifies sensitivity to ionizing radiation.
AB  - Phosphorylation is an important modification involved in the control of p53
      activity. We examined the relationship between p53 phosphorylation and cell
      radiosensitivity. We prepared H1299 cells (p53-null) with various mutations of
      p53 at three sites (serine 15, 20 and 46) and examined the radiosensitivity of
      the cells. In three mutant forms of p53--S15A, S20A and S46A--serine was
      converted to alanine at these sites to prevent phosphorylation, and in two other
      mutant forms, S15D and S20D, serine was converted to aspartic acid to mimic
      phosphorylation. H1299 cells were more radioresistant than cells with wild-type
      p53. Cells with the S15A and S46A mutant forms of p53 were radiosensitive,
      whereas those with the S15D, S20A and S20D forms showed medium radiosensitivity.
      Thus the sensitivity of cells to ionizing radiation varies according to the site
      of phosphorylation of p53.

PMID- 21737650
TI  - Association of C-reactive protein (CRP) gene polymorphisms, serum CRP levels and
      cervical cancer prognosis.
AB  - BACKGROUND: C-reactive protein (CRP) is the prototypical biomarker of
      inflammation. Genetic variations within the CRP gene have been shown to be
      associated with alterations of CRP expression and prognosis in cancer patients.
      The purpose of this study was to evaluate the association between four
      polymorphisms of the CRP gene, CRP serum levels, clinicopathological parameters
      of cervical cancer and survival in patients with cervical cancer. MATERIALS AND
      METHODS: The four most common single nucleotide gene polymorphisms CRP1919
      (rs1417938), CRP2667 (rs1800947), CRP3872 (rs1205), and CRP5237 (rs2808630) were
      evaluated in 178 patients with cervical cancer. DNA was extracted from blood
      samples and CRP gene polymorphisms were investigated, using pyrosequencing.
      Findings were correlated with CRP serum levels, clinico-pathological parameters
      of cervical cancer, and disease-free and overall survival. Furthermore, the
      association between haplotype combinations and survival was investigated.
      RESULTS: Presence of the CRP gene polymorphism CRP5237A>G was associated with
      lower CRP serum levels (p=0.04). Univariate survival analysis revealed that
      CRP1919T>A polymorphism (p=0.02), International Federation of Gynecology and
      Obstetrics stage (p<0.001), lymph node involvement (p=0.004), histological grade
      (p=0.01), and serum CRP levels (p<0.001) correlate with overall survival. In the
      multivariable Cox regression model, CRP1919T>A (p=0.02), tumor stage (p<0.001),
      lymph node involvement (p=0.03), patients' age (p=0.02), and serum CRP levels
      (p<0.001) were found to be independently associated with overall survival. None
      of the haplotype combinations were associated with prognosis of patients with
      cervical cancer. CONCLUSION: Presence of the CRP1919T>A polymorphism was
      associated with impaired overall survival in patients with cervical cancer. The
      CRP gene polymorphism CRP5237A>G was associated with decreased serum CRP levels.

PMID- 21737651
TI  - Induction treatment for diffuse intrinsic pontine glioma, experience of M.D.
      Anderson Cancer Center.
AB  - BACKGROUND: The biology of diffuse intrinsic pontine glioma remains poorly
      understood and the dismal prognosis has not changed despite various attempts to
      add chemotherapy to standard radiation. PATIENTS AND METHODS: A retrospective
      chart review was carried out of patients with diffuse intrinsic pontine glioma
      treated at M.D. Anderson Cancer Center from 1998 to 2010, and the data analyzed
      comparing drug effects aiming to generate hypotheses. RESULTS: A total of 64
      patients had diffuse intrinsic pontine glioma as confirmed by radiology review;
      28 were male, and age at diagnosis ranged from 1.5 to 16.5 years. All patients
      received radiation as initial treatment, and 44 had additional treatment during
      the radiation, with a total of 15 different drug combinations obtained from 15
      different individual drugs. The median overall survival after diagnosis was 0.79
      years (SD 0.123). Patients treated with the anti-inflammatory agent rofecoxib had
      inferior survival (p=0.00002). CONCLUSION: Based on these data, we hypothesize
      that inflammatory/reactive processes in the tumor might play a beneficial role
      during radiation and suggest that this be tested in animal models.

PMID- 21737652
TI  - Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for
      advanced colorectal cancer.
AB  - AIM: The feasibility of an alternating regimen of BIBF 1120, a potent, oral,
      triple angiokinase inhibitor, and afatinib (BIBW 2992), a potent ErbB family
      blocker, was explored in patients with advanced pretreated colorectal cancer
      (CRC). PATIENTS AND METHODS: Patients received repeated courses of alternating 7
      day treatment periods, first with BIBF 1120 250 mg twice daily and then afatinib
      50 mg once daily. The primary endpoint was the objective response rate; the
      incidence/severity of adverse events (AEs) and pharmacokinetics (PK) were
      determined. RESULTS: Forty-six patients (>=4 prior lines, most anti-VEGF and/or 
      EGFR pretreated) received BIBF 1120 and afatinib. No objective responses were
      observed; the best response was stable disease in 20 patients (43.5%). Seven
      patients (15.2%) remained progression-free for >=16 weeks. Median progression
      free survival was 1.9 months; median overall survival was 5.5 months. The most
      frequent drug-related AEs were diarrhoea (80.4%), asthenia (47.8%), nausea
      (43.5%) and rash (41.3%). PK assessments did not show obvious alterations for
      either drug. CONCLUSION: Weekly alternating administration of BIBF 1120 and
      afatinib is feasible; however, its efficacy was limited in this highly palliative
      patient population.

PMID- 21737653
TI  - Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis,
      progression and therapy.
AB  - Endoglin (CD105) is an accessory receptor for transforming growth factor beta
      (TGF-beta) and its expression is up-regulated in actively proliferating
      endothelial cells. Endoglin has been suggested as an appropriate marker for tumor
      related angiogenesis and neovascularization. Several studies demonstrate the
      potential of endoglin in tumor diagnosis, prognosis, and therapy. This review
      details the structure and function of endoglin, and investigates the role of
      endoglin in angiogenesis and tumor diagnosis, prognosis, and therapy.

PMID- 21737654
TI  - Percutaneous radiofrequency ablation of hepatocellular carcinoma compared to
      percutaneous ethanol injection in treatment of cirrhotic patients: an Italian
      randomized controlled trial.
AB  - AIM: To compare 5-year survival of patients with a single hepatocellular
      carcinoma<=3 cm randomly assigned to receive percutaneous ethanol injection or
      radiofrequency ablation. PATIENTS AND METHODS: A total of 285 patients (192
      males, mean age 70 years), with a single hepatocellular carcinoma (mean diameter
      2.2 cm) were randomly assigned to receive percutaneous ethanol injection (n=143)
      or radiofrequency ablation (n=142). The primary endpoint of the study was 5-year
      survival. RESULTS: Overall 143 patients underwent percutaneous ethanol injection
      and 128 radiofrequency ablation. In consideration of segmental location, in fact,
      14 patients with 14 hepatocellular carcinomas could not be treated with
      established radiofrequency and were treated with percutaneous ethanol injection;
      these patients were not included in the survival evaluation. In the percutaneous
      ethanol injection and in the radiofrequency ablation groups, 3- and 5-year
      survival rates of 74% and 68%, and 78% and 68%, and 79% and 70% [corrected]
      respectively, were observed (p=n.s). In the percutaneous ethanol injection group,
      3- and 5-year local recurrence rates were 9.4% and 12.8% respectively; in the
      radiofrequency group, the 3 and 5 years local recurrence rates were 7.8% and
      11.7%, respectively (p=n.s.). The overall costs of percutaneous ethanol injection
      and radiofrequency ablation were 1359 Euros and 171.000 Euros, respectively
      (p<0.0001) CONCLUSION: Percutaneous ethanol injection and radiofrequency ablation
      conferred similar 5-year survival. Feasibility is not the same for both
      procedures. Percutaneous ethanol injection is much cheaper than radiofrequency
      ablation and should be considered whether in poor and rich countries.

PMID- 21737655
TI  - Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or
      relapsed multiple myeloma: once-weekly administration of bortezomib may reduce
      the incidence of gastrointestinal adverse events.
AB  - BACKGROUND: To establish the clinical use of bortezomib with fewer adverse
      events, we retrospectively analyzed the efficacy and safety of bortezomib plus
      dexamethasone (BD) therapy for relapsed or refractory multiple myeloma. PATIENTS
      AND METHODS: Patients received bortezomib (1.3 mg/m2) as an intravenous bolus on
      days 1, 4, 8 and 11 in a 3-week cycle (twice-weekly administration), or on days
      1, 8, 15 and 22 in a 5-week cycle (once-weekly administration). Dexamethasone (20
      mg) was given on the day of and day after bortezomib treatment. RESULTS: From
      January 2007 to July 2010, 22 patients began to receive BD therapy. Initially,
      bortezomib was administered twice-weekly, but some severe adverse events
      developed; therefore, from January 2008, bortezomib was administered twice-weekly
      for the first two courses, followed by once-weekly for the subsequent courses.
      Patients who were expected to have severe adverse events beforehand were treated
      initially with once-weekly administration. Of the 22 patients, 14 were treated
      with twice-weekly followed by once-weekly administration, five with only twice
      weekly administration and three with only once-weekly administration. Seventeen
      patients (77.3%) achieved at least partial response, including three with
      complete response and seven with very good partial response. The median
      progression-free survival and the median overall survival of 22 patients were 512
      days and not reached, respectively. The median progression-free survival and the
      median overall survival of 17 patients who received at least one course of once
      weekly administration were 615 days and not reached, respectively. The most
      frequent >=grade 3 adverse events with twice-weekly administration were
      gastrointestinal, especially paralytic ileus and constipation. Among seven
      patients who developed >=grade 3 gastrointestinal adverse events with twice
      weekly administration, all four patients changed the schedule to once-weekly were
      able to continue BD therapy. CONCLUSION: Once-weekly administration of bortezomib
      in BD therapy may reduce the incidence of gastrointestinal adverse events without
      reducing the clinical efficacy of this therapy for refractory or relapsed
      multiple myeloma.

PMID- 21737656
TI  - Identification of polymorphisms associated with hypertriglyceridemia and
      prolonged survival induced by bexarotene in treating non-small cell lung cancer.
AB  - BACKGROUND: Bexarotene was evaluated in treating advanced non small cell lung
      cancer (NSCLC) in two phase III trials. Although a significant survival benefit
      was not observed for the overall bexarotene-treated population (617 patients), a
      third of bexarotene-treated patients who developed high-grade
      hypertriglyceridemia exhibited significantly longer survival. PATIENTS AND
      METHODS: In order to identify genomic polymorphisms that could serve as potential
      predictive biomarkers for response and improved survival in NSCLC patients, DNA
      samples extracted from plasma archived from 403 patients were genotyped using
      Affymetrix 500K whole genome SNP arrays and/or Sequenom iPLEXTM assays. RESULTS:
      Fourteen SNPs were identified on nine loci that showed significant associations
      with high-grade hypertriglyceridemia induced by bexarotene. Four such single
      nucleotide polymorphisms (SNPs) reside on the region upstream of solute carrier
      family 10, member 2 (SLC10A2), and one SNP is located close to lymphocyte
      cytosolic protein 1 (LCP1), whose expression correlated with the activity of
      bexarotene in tumor cells. CONCLUSION: We identified novel polymorphisms
      exhibiting significant association with bexarotene induced hypertriglyceridemia,
      implicating their potential in predicting bexarotene-improved survival response.

PMID- 21737657
TI  - Surgical management of bisphosphonate-related osteonecrosis of the jaw in
      oncologic patients: a challenging problem.
AB  - AIM: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious oral
      complication of supportive cancer therapy and the best method of treatment is
      still unclear. The purpose of this article is to analyze the type of treatment
      and outcome in a large patient cohort with BRONJ. PATIENTS AND METHODS: A total
      of 142 patients suffering from BRONJ at different sites were studied. All
      patients had been treated with intravenous bisphosphonates for various
      oncological disease. A descriptive analysis of all relevant patient data was
      performed with particular emphasis on surgical outcome. RESULTS: The mandible was
      affected in 58% of the patients. All but two patients had previous invasive
      dental procedures. The mean duration of bisphosphonate treatment was 37.1 months.
      A total of 86% of the patients were treated surgically, including
      sequestrectomies and mandibular resections. Soft-tissue reconstruction was
      achieved by local closure, myofascial flap using the mylohyoid muscle, and a
      vascularized fasciocutaneous flap in one patient. No bony reconstruction was
      performed. CONCLUSION: Surgical treatment of BRONJ remains challenging. There is
      only limited evidence that oncologic patients with BRONJ are candidates for
      vascularized bone reconstruction.

PMID- 21737658
TI  - Expression of iNOS--a favourable prognostic marker for early-stage carcinoma of
      the uterine cervix.
AB  - In former studies, raised urine cGMP levels have been reported to predict adverse
      outcome in cervical cancer. The main objective of the present study was to
      investigate the value of nitric oxide synthase (iNOS) and other members of the
      cGMP pathway as potential biomarkers for prognosis of cervical carcinoma. Tissue
      samples from 85 patients surgically treated for early-stage cervical carcinoma
      were immunohistochemically stained for iNOS, soluble guanylyl cyclase subunits
      alpha1 (sGC-alpha1), soluble guanylyl cyclase alpha2 (sGC-alpha2), and
      phosphodiesterase 5, each sample evaluated microscopically by a semi-quantitative
      score. Results were correlated to recurrence and FIGO stage (depth of tumour cell
      infiltration). Correlation was found between high expression of iNOS in tumour
      cells and low risk of recurrence (p=0.019, p=0.05, p=0.022 and p=0.025). High
      expression of iNOS, sGC-alpha1 and sGC-alpha2 also correlated to superficial
      tumour growth. Our results demonstrate that iNOS expression in cervical tumour
      tissue is a robust prognostic marker for cervical cancer.

PMID- 21737659
TI  - Mammographic features are associated with clinicopathological characteristics in
      invasive breast cancer.
AB  - AIM: To assess the correlation between mammographic features and
      clinicopathologic characteristics of invasive breast carcinoma. PATIENTS AND
      METHODS: The mammographic appearance and clinicopathological data of 108 invasive
      ductal carcinomas were retrospective analyzed. The mammographic features were
      assessed according to BI-RADS by two doctors. Estrogen receptor (ER),
      progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2) and
      Ki-67 were analyzed on the surgically removed tumor samples by
      immunohistochemical staining analysis. The clinical information, including age,
      menopausal status, tumor size, grade, stage, and axillary lymph node status, were
      collected from our database. Statistical analysis was performed to assess the
      correlation between mammographic features and clinicopathologic characteristics.
      RESULTS: Based on pathologic analysis, 19 out of the 108 (18%) patients had
      invasive ductal carcinoma (IDC) accompanied by component of ductal carcinoma in
      situ (DCIS); another 89 cases (82%) were pure IDC. Sixty-three patients had a
      mass on the mammogram; the mammographically visible mass was frequently observed
      in histologically pure IDC, while mammographic calcification was significantly
      associated with IDC accompanied with DCIS (p<0.01). Mammographic calcification
      accompanied by evident mass was correlated with axillary lymph node metastasis
      (p<0.05). The tumor size was usually larger than 2 cm when the mammographic mass
      was accompanied by calcification (p<0.01). Tumors from patients presenting with
      spiculated mass had a significantly higher ER-positive and PR-positive rates than
      those from patients presenting with non-spiculated mass (92.59% vs. 63.89%,
      p<0.01, and 92.59% vs. 44.44%, p<0.01, respectively). Tumors from patients
      presenting with spiculated mass had Her2 negativity (p<0.05) and lower
      proliferative activity as labeled by Ki-67 compared with those from patients
      presenting with non-spiculated mass (p<0.01). CONCLUSION: Based on our current
      findings, the mammographic appearance reflects the biologic behavior of the
      breast tumor and should be taken into account when planning treatment for IDC.

PMID- 21737660
TI  - Response of recurrent urachal cancer to gemcitabine and cisplatin therapy: a case
      report and literature review.
AB  - Urachal cancer is a rare malignancy and the standard treatment is surgical
      resection. The prognosis of recurrent and metastatic urachal cancer is extremely
      poor because there is no established chemotherapy regimen. Here, the response of
      one patient with recurrent urachal cancer to combination chemotherapy of
      gemcitabine (GEM) and cisplatin (CDDP) (GC) is described. And the chemo- and
      radiotherapeutic regimens available for such patients are reviewed. A 67-year-old
      man diagnosed with stage IIIA urachal cancer underwent complete surgical
      resection. However, pelvic recurrence was detected on computed tomography (CT) 5
      months after surgery. GC therapy was started immediately and resulted in a
      pronounced reduction in pelvic mass after three cycles. However, a follow-up CT
      scan taken 5 months later showed growth of the pelvic mass and new liver
      metastasis. He received GC therapy again, which resulted in reduction of the
      pelvic and liver metastatic masses after two cycles. However, the patient refused
      another course of GC therapy due to severe side-effects. Subsequent progression
      of the disease included spread in both regions, followed by death 16 months after
      recurrence. Various treatment strategies offer relatively long survival of
      patients with urachal cancer including those with recurrence and metastasis.
      Although further studies are necessary to determine its therapeutic efficacy, GC
      therapy may be a useful option in the treatment of urachal tumors, including
      recurrent tumours.

PMID- 21737661
TI  - Complete response to chemoradiotherapy in a patient with synchronous double
      gastric and esophageal cancer.
AB  - A 77-year-old man with early synchronous double primary gastric and esophageal
      cancer showed complete response (CR) to chemoradiotherapy (CRT) with fluorouracil
      (5-FU) and cis-diamminedichloroplatinum (CDDP) and 60 Gy total dose of radiation.
      Gastrointestinal endoscopy had revealed type IIc squamous cell carcinoma in the
      lower oesophagus and type IIc adenocarcinoma in the mid-stomach region.
      Synchronous double primary early-stage esophageal and gastric cancer was
      diagnosed. The patient's age and chronic obstructive pulmonary disease (COPD)
      contraindicated radical esophageal surgery. Therefore, we decided to first
      administer CRT with 5-FU and CDDP for the esophageal cancer, and subsequently
      perform partial gastrectomy for the gastric cancer. After the CRT, neither of the
      tumors recurred. CR to CRT for the esophageal cancer and CR to chemotherapy for
      the gastric cancer were achieved. CONCLUSION: CRT with 5-FU and CDDP can produce
      CR in cases of early esophageal and gastric cancer.

PMID- 21737662
TI  - Spreading of acute myeloid leukemia cells by trafficking along the peripheral
      outflow pathway of cerebrospinal fluid.
AB  - Acute myeloid leukemia (AML) can affect not only bone marrow (BM) and peripheral
      blood (PB), but also the compartment of cerebrospinal fluid (CSF). Besides
      standard chemotherapy, specific and non-specific immunotherapy has been employed
      synergistically to treat AML patients. Here we report on a patient who received
      standard chemotherapy, unspecific immunotherapy with interleukin-2, as well as
      later specific CD8+ T-cell stimulation by RHAMM-R3 peptide vaccination. The
      patient maintained a complete remission in BM and PB, while he developed
      recurrent relapses in the CSF. Moreover, the patient developed a chloroma in the
      vicinity of neuronal sheaths during hematological CR, but high leukemia cell
      numbers within the CSF spaces over a long time period. This rare observation
      demonstrates several aspects. There is a previously unknown site of leukemia cell
      distribution, namely the peripheral cerebrospinal outflow pathway (PCOP). This
      demonstrates the ineffective therapy of this previously unknown mechanism of
      leukemia cell spread. The hypothesis that the PCOP is a site of physiological CSF
      T-cell trafficking, and the lumen of the PCOP should be considered as an
      extension of the subarachnoidal spaces without closed anatomical borders is
      supported by this observation. The CSF spaces, but possibly specifically the
      PCOP, may represent a previously unknown survival niche of tumor cells within
      intrathecal spaces.

PMID- 21737663
TI  - Variations in demography and prognosis by colon cancer location.
AB  - AIM: Tumours of the right and left colon are suggested to be different entities
      with different prognosis. The aim was to explore differences related to the
      location of a colonic tumour. PATIENTS AND METHODS: A single-centre retrospective
      analysis of all patients treated for colon cancer during 1999-2008 (n=1558) was
      carried out. Assessed data included demography, pathology and survival by cancer
      location, with left colon also sub-divided into left and sigmoid colon. RESULTS:
      Right colon carcinoma was associated with female gender, higher age and poor
      grade of differentiation; left colon carcinoma had characteristics of worse
      stages and requiring emergency surgery. Sigmoid tumours were of better grade and
      stage. Survival was related the staging, which varied with location. Right colon
      carcinoma conferred a worse overall survival (OS) (p<0.037) but not cancer
      specific survival (CSS) or disease-free survival compared to the entire left
      colon, whilst sigmoid tumours conferred a better OS and CSS (p<0.001) when the
      left colon was sub-divided. CONCLUSION: There are differences in demography and
      pathology related to the location of colon cancer. Sigmoid location carries the
      best prognosis.

PMID- 21737664
TI  - Clinical significance of HIF-1alpha expression in patients with esophageal cancer
      treated with concurrent chemoradiotherapy.
AB  - AIM: We investigated whether hypoxia-inducible factor-1alpha (HIF-1 alpha)
      expression in pretreatment biopsies of esophageal cancer is predictive of
      clinical outcome in patients with esophageal cancer undergoing concurrent
      chemoradiotherapy (CRT). PATIENTS AND METHODS: A total of 25 patients were
      reviewed. Radiotherapy was administered to total doses of 40-66.6 Gy (median:
      66.6 Gy) with a single fraction of 1.8-2 Gy. Cisplatin (80 mg/m2 on day 1) and 5
      fluorouracil (800 mg/m2 on days 2-6) were administered concurrently with
      radiotherapy, every 3-4 weeks to a total of 1-2 courses. Tissue samples from
      esophageal cancer were obtained from all 25 patients by biopsy before concurrent
      CRT, and semiquantitative analyses of HIF-1alpha expression were performed using
      immunohistochemical staining. RESULTS: High HIF-1alpha expression was observed in
      11 out of 25 patients (42.7%), and HIF-1alpha expression was significantly
      correlated with initial response to CRT (p=0.0027). Patients with high HIF-1alpha
      expression had significantly poorer local control (LC) (5-year LC: 42.7%) than
      those with low expression (5-year LC: 72.5%; p=0.0322). Patients with high HIF
      1alpha expression also had significantly lower recurrence-free survival (RFS) (5
      year RFS: 18.2%) compared to those with low HIF-1alpha expression (5-year RFS:
      39.8%; p=0.0009), and on multivariate analysis, HIF-1alpha (p=0.001) and number
      of chemotherapy courses (p=0.010) were independent prognostic factors for RFS.
      CONCLUSION: HIF-1alpha expression is significantly correlated with initial
      response to concurrent CRT, and is predictive of RFS for patients with esophageal
      cancer receiving concurrent CRT.

PMID- 21737665
TI  - Comparison of staging between the old (6th edition) and new (7th edition) TNM
      classifications in advanced gastric cancer.
AB  - BACKGROUND: The aims of the present study were to compare staging between the old
      (6th edition) and new (7th edition) TNM classifications, and to evaluate the
      prognostic impact of extended lymph node dissection according to the new nodal
      staging in advanced gastric cancer. PATIENTS AND METHODS: A total of 609 patients
      with advanced gastric cancer who had undergone curative gastric resection
      combined with extended lymph node dissection were enrolled in the present study.
      Survival curves were analyzed according to staging based on the TNM 6th and 7th
      editions and the Japanese Classification of Gastric Carcinoma (JCGC) 14th
      edition. RESULTS: The 5-year survival rates and the consecutive stage survival
      with no significant differences were: IB 88%; II 74%; IIIA 53%; IIIB 39%; and IV
      18% (IIIA vs. IIIB, p=0.1307) by the TNM 6th edition; IB 94%; IIA 85%; IIB 71%;
      IIIA 68%; IIIB 48%; IIIC 23%; and IV 13%; (IIB vs. IIIA, p=0.7665; IIIC vs. IV,
      p=0.4156) by the TNM 7th and JCGC 14th editions; N0 85%; N1 70%; N2 46%; N3 18%;
      and M1 13%; (N3 vs. M1, p=0.8640) by the TNM 6th edition; and N0 85%; N1 80%; N2
      61%; N3a 46%; N3b 18%; and M1 13%; (N0 vs. N1, p=0.2735; N2 vs. N3a, p=0.0663;
      N3b vs. M1, p=0.8640) by the TNM 7th and JCGC 14th editions. CONCLUSION: The new
      classification according to the TNM 7th and the JCGC 14th editions does not
      always seem to be superior to the TNM 6th edition for the prognostic
      stratification of stages in patients who undergo curative resection for advanced
      gastric cancer. An extended lymph node dissection may be effective for N0-N3a,
      but not for N3b and M1 stages classified according to the new TNM 7th and JCGC
      14th editions.

PMID- 21737666
TI  - Case report of a poorly differentiated uterine tumour with t(10;17) translocation
      and neuroectodermal phenotype.
AB  - Endometrial stromal sarcoma (ESS) with primitive neuroectodermal differentiation
      is a very uncommon entity. Such a case presenting as stage IIIc (International
      Federation of Gynaecology and Obstetrics (FIGO) 2010) disease in a 51-year-old
      female is described. Microscopy suggested a small blue round cell tumour.
      Cytogenetic and multicolour fluorescent in situ hybridisation (M-FISH) analysis
      revealed a complex karyotype with the presence of unbalanced t(10;17)(q22;p13)
      translocation, indicating ESS. Peripheral Ewing's sarcoma was excluded based on
      FISH and RT-PCR fusion transcripts analysis. After surgical staging, the patient
      received bleomycin-etoposide-cisplatin combination chemotherapy. A detailed
      analysis of the histopathology and genetic findings forms the basis of this
      report.

PMID- 21737667
TI  - Cutaneous metastasis of signet-ring gastric adenocarcinoma to the breast with
      unusual clinicopathological features.
AB  - BACKGROUND: Cutaneous metastasis of gastric adenocarcinoma is rare and usually
      presents in men, as nodules over the abdomen. We present the case of a woman with
      cutaneous metastasis of gastric adenocarcinoma showing unusual
      clinicopathological features. CASE REPORT: A 37-year-old woman developed florid
      cutaneous metastasis over the skin of the left breast two years after total
      gastrectomy for a signet-ring adenocarcinoma of the diffuse type. The metastasis
      presented as a multinodular growth developing over erythematous skin of the left
      hemithorax. Microscopically, the skin tumor was predominantly made up of spindle
      shaped cells, mimicking a mesenchymal/fibrohistiocytic neoplasm. A comparative
      immunohistochemical study of the gastric primary and the skin tumor showed an
      almost identical profile (keratin 7/20+; epithelial membrane antigen+, MUC-5AC+),
      highlighting the gastric adenocarcinoma as the origin of the skin metastasis.
      CONCLUSION: Although rare, cutaneous metastases of gastric adenocarcinomas can
      develop in women and may mimic inflammatory metastasis of breast adenocarcinoma.
      Immunohistochemistry is invaluable in establishing the correct diagnosis.

PMID- 21737668
TI  - Docetaxel, cisplatin and 5-fluorouracil plus granulocyte colony-stimulating
      factor prophylaxis in patients with metastatic adenocarcinoma of the stomach and
      gastroesophageal junction: experience at the Medical University of Vienna.
AB  - BACKGROUND: A retrospective analysis was carried out to evaluate toxicity and
      efficacy of the combination chemotherapy of docetaxel, cisplatin and 5
      fluorouracil (DCF) plus granulocyte colony-stimulating factor prophylaxis (G-CSF)
      in patients with metastatic gastric and gastroesophageal junction adenocarcinoma.
      PATIENTS AND METHODS: Eighteen patients received intravenous 75 mg/m2 docetaxel,
      75 mg/m2 cisplatin, both given on day 1 and 750 mg/m2 5-fluorouracil, on days 1
      to 5 plus G-CSF on day 6, all repeated every 3 weeks. RESULTS: Response rate was
      28%, time to progression and overall survival were 26 and 54 weeks, respectively.
      The most common hematological WHO toxicities were anemia and leukocytopenia,
      which occurred in 18/18 and in 12/18 patients. WHO Grade 4 neutropenia occurred
      in one patient whereas nonhematological toxicity was generally mild. CONCLUSION:
      We conclude that DCF combination plus G-CSF prophylaxis is a safe and active
      regimen for patients with metastatic gastric and gastroesophageal junction
      adenocarcinoma.

PMID- 21737669
TI  - Incidence of venous thromboembolism during chemotherapy for breast cancer: impact
      on cancer outcome.
AB  - BACKGROUND: Evidence suggests that cancer patients who develop venous
      thromboembolism (VTE) have a poorer outcome than those who do not. The aim of
      this prospective study was to assess the incidence of the development of VTE in
      breast cancer patients commencing chemotherapy and the relationship between
      development of thrombosis and cancer progression and death. PATIENTS AND METHODS:
      One hundred and thirty-four breast cancer patients were recruited and followed up
      prior to chemotherapy and at 3, 6, 12 and 24 months. Duplex ultrasound imaging
      (DUI) was performed 1 month following commencement of chemotherapy or if patients
      became symptomatic. RESULTS: Thirteen patients developed VTE. Six patients with
      advanced breast cancer and seven with early breast cancer developed VTE. Three
      patients died from VTE; all had advanced breast cancer. In patients with VTE, the
      28-day mortality rate was 15%, but in patients with symptomatic VTE, the 28-day
      mortality was 22%. Development of VTE did not predict for progression by three
      and six months in advanced breast cancer patients. VTE demonstrated a trend for
      predicting progression by two years. Using Cox regression survival analysis,
      there was no survival advantage in those with or without VTE. CONCLUSION:
      Although the body of evidence supports a worse prognosis when VTE and cancer
      coexist as compared to either diagnosis alone, a larger prospective study is
      required to confirm this and clarify whether any premature death is primarily due
      to VTE or to more aggressive cancer.

PMID- 21737670
TI  - Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative
      breast cancer.
AB  - BACKGROUND: Elucidation of the biological features of triple negative breast
      cancer (TNBC) is important for deciding treatment strategies. The expression of a
      number of biomarkers in TNBC was analyzed to elucidate those features. PATIENTS
      AND METHODS: The subjects were 134 TNBC patients. Immunohistochemical staining
      was employed to analyze for eight biomarkers: cytokeratin 5/6 (CK5/6), epidermal
      growth factor receptor (EGFR), p53, Ki-67 antigen (Ki-67), E-cadherin, N
      cadherin, topoisomerase 2 alpha (TOP2A) and B-cell lymphoma 2 (BCL-2), which were
      then correlated with the nuclear grade (NG), tumor diameter, and the
      presence/absence of lymph node metastasis, distant recurrence and lymphatic
      infiltration. RESULTS: Significantly more high than low NG TNBC exhibited
      positive p53, Ki-67, E-cadherin and TOP2A. High N-cadherin and TOP2A expression
      was shown significantly in TNBC with lymphatic infiltration, and N-cadherin was
      also significantly positively expressed in node metastasis-positive cases. EGFR
      and CK5/6 were positively expressed in high NG TNBC, but not significantly.
      CONCLUSION: Analysis for expression of p53, Ki-67, E-cadherin, N-cadherin and
      TOP2A is meaningful for deciding treatment strategies for TNBC.

PMID- 21737671
TI  - Methylenetetrahydrofolate reductase (MTHFR) genotype, smoking habit, metastasis
      and oral cancer in Taiwan.
AB  - The aim of this study was to evaluate the association and interaction of
      genotypic polymorphism in methylenetetrahydrofolate reductase (MTHFR) with
      smoking habits and oral cancer in Taiwan. Two well-known polymorphic variants of
      MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed in association
      with oral cancer risk, and their joint effects with individual smoking habits on
      oral cancer risk are discussed. In total, 620 oral cancer patients and 620 non
      cancer controls in central Taiwan were recruited and genotyped. The MTHFR C677T
      genotype, but not the A1298C, was differently distributed between the oral cancer
      and control groups. The T allele of MTHFR C677T was significantly more frequently
      found in controls than in oral cancer patients. Joint effects of smoking and
      MTHFR C677T genotype significantly affected oral cancer susceptibility. The MTHFR
      C677T CT and TT genotypes in association with smoking conferred lower odds ratios
      of 0.66 and 0.54 (95% confidence interval=0.49-0.82 and 0.39-0.86), respectively.
      Those patients with MTHFR C677T CT and TT genotypes also had a lower risk of oral
      cancer metastasis. MTHFR C677T genotype may have joint effects with smoking on
      oral carcinogenesis, and may be a useful biomarker for prediction and prognosis
      of oral cancer.

PMID- 21737672
TI  - Introduction of a guide to enhance risk communication among low-income and
      minority populations: a grassroots community engagement approach.
AB  - Low-income populations, especially those belonging to minority groups, are among
      the most vulnerable groups before, during, and after a natural disaster. One of
      the factors that can be attributed to their vulnerability is the ineffectiveness
      of traditional risk communication systems in reaching this population. Many low
      income populations are distrustful of government agencies and those who typically
      communicate risk messages. Consequently, traditional systems are not as effective
      in reaching these communities. Furthermore, traditional systems have been based
      on the social media that the general population uses and not based on social
      networks of disadvantaged populations which are more important than formal
      channels in these communities for dissemination of information. To bridge the
      gap, an approach is needed that relies on trusted agencies and leaders to educate
      and warn low-income communities about possible public health threats. A
      grassroots approach can enhance the capacity of the risk communication systems to
      more effectively reach vulnerable populations by engaging grassroots
      organizations in risk communication activities. The Guide to Enhance Grassroots
      Risk Communication Among Low-Income Populations provides strategies and guidance
      that can assist agencies in upgrading their systems for risk communication by
      building partnerships with local community stakeholders.

PMID- 21737674
TI  - An evolutionarily conserved Rit GTPase-p38 MAPK signaling pathway mediates
      oxidative stress resistance.
AB  - Ras-related small GTP-binding proteins control a wide range of cellular processes
      by regulating a variety of effector pathways, including prominent roles in the
      control of mitogen-activated protein kinase (MAPK) cascades. Although the
      regulatory role(s) for many Ras family GTPases are well established, the
      physiological function for the Rit/Rin subfamily has been lacking. Here, using
      both knockout mice and Drosophila models, we demonstrate an evolutionarily
      conserved role for Rit subfamily GTPases (mammalian Rit and Rin, and the
      Drosophila RIC homologue) in governing survival in response to oxidative stress.
      Primary embryonic fibroblasts derived from Rit knockout mice display increased
      apoptosis and selective disruption of MAPK signaling following reactive oxygen
      species (ROS) exposure but not in response to endoplasmic reticulum stress or DNA
      damage. These deficits include a reduction in ROS-mediated stimulation of a p38
      MK2-HSP27 signaling cascade that controls Akt activation, directing Bad
      phosphorylation to promote cell survival. Furthermore, D-RIC null flies display
      increased susceptibility to environmental stresses and reduced stress-dependent
      p38 signaling, extending the Rit-p38 survival pathway to Drosophila. Together,
      our studies establish the Rit GTPases as critical regulators of an evolutionarily
      conserved, p38 MAPK-dependent signaling cascade that functions as an important
      survival mechanism for cells in response to oxidative stress.

PMID- 21737673
TI  - The reconstructed ancestral subunit a functions as both V-ATPase isoforms Vph1p
      and Stv1p in Saccharomyces cerevisiae.
AB  - The vacuolar-type, proton-translocating ATPase (V-ATPase) is a multisubunit
      enzyme responsible for organelle acidification in eukaryotic cells. Many
      organisms have evolved V-ATPase subunit isoforms that allow for increased
      specialization of this critical enzyme. Differential targeting of the V-ATPase to
      specific subcellular organelles occurs in eukaryotes from humans to budding
      yeast. In Saccharomyces cerevisiae, the two subunit a isoforms are the only
      difference between the two V-ATPase populations. Incorporation of Vph1p or Stv1p
      into the V-ATPase dictates the localization of the V-ATPase to the vacuole or
      late Golgi/endosome, respectively. A duplication event within fungi gave rise to
      two subunit a genes. We used ancestral gene reconstruction to generate the most
      recent common ancestor of Vph1p and Stv1p (Anc.a) and tested its function in
      yeast. Anc.a localized to both the Golgi/endosomal network and vacuolar membrane
      and acidified these compartments as part of a hybrid V-ATPase complex.
      Trafficking of Anc.a did not require retrograde transport from the late endosome
      to the Golgi that has evolved for retrieval of the Stv1p isoform. Rather, Anc.a
      localized to both structures through slowed anterograde transport en route to the
      vacuole. Our results suggest an evolutionary model that describes the
      differential localization of the two yeast V-ATPase isoforms.

PMID- 21737675
TI  - Regulation of exit from mitosis in multinucleate Ashbya gossypii cells relies on
      a minimal network of genes.
AB  - In Saccharomyces cerevisiae, mitosis is coupled to cell division by the action of
      the Cdc fourteen early anaphase release (FEAR) and mitotic exit network (MEN)
      regulatory networks, which mediate exit from mitosis by activation of the
      phosphatase Cdc14. The closely related filamentous ascomycete Ashbya gossypii
      provides a unique cellular setting to study the evolution of these networks.
      Within its multinucleate hyphae, nuclei are free to divide without the spatial
      and temporal constraints described for budding yeast. To investigate how this
      highly conserved system has adapted to these circumstances, we constructed a
      series of mutants lacking homologues of core components of MEN and FEAR and
      monitored phenomena such as progression through mitosis and Cdc14 activation. MEN
      homologues in A. gossypii were shown to have diverged from their anticipated role
      in Cdc14 release and exit from mitosis. We observed defects in septation, as well
      as a partial metaphase arrest, in Agtem1Delta, Agcdc15Delta, Agdbf2/dbf20Delta,
      and Agmob1Delta. A. gossypii homologues of the FEAR network, on the other hand,
      have a conserved and more pronounced role in regulation of the M/G1 transition.
      Agcdc55Delta mutants are unable to sequester AgCdc14 throughout interphase. We
      propose a reduced model of the networks described in yeast, with a low degree of
      functional redundancy, convenient for further investigations into these networks.

PMID- 21737676
TI  - The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell
      growth, survival, and migration.
AB  - The NF-kappaB family of transcription factors is a well-established regulator of
      the immune and inflammatory responses and also plays a key role in other cellular
      processes, including cell death, proliferation, and migration. Conserved residues
      in the trans-activation domain of RelA, which can be posttranslationally
      modified, regulate divergent NF-kappaB functions in response to different
      cellular stimuli. Using rela(-/-) mouse embryonic fibroblasts reconstituted with
      RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine
      has wide-ranging effects on NF-kappaB function. These include previously
      described effects on chemotherapeutic drug-induced apoptosis, as well as new
      roles for this modification in autophagy, cell proliferation, and migration. This
      last effect was associated with alterations in the actin cytoskeleton and
      expression of cellular migration-associated genes such as WAVE3 and alpha-actinin
      4. We also define a new component of cisplatin-induced, RelA T505-dependent
      apoptosis, involving induction of NOXA gene expression, an effect explained at
      least in part through induction of the p53 homologue, p73. Therefore, in contrast
      to other RelA phosphorylation events, which positively regulate NF-kappaB
      function, we identified RelA T505 phosphorylation as a negative regulator of its
      ability to induce diverse cellular processes such as apoptosis, autophagy,
      proliferation, and migration.

PMID- 21737677
TI  - Deciphering the rules governing assembly order of mammalian septin complexes.
AB  - Septins are conserved GTP-binding proteins that assemble into lateral diffusion
      barriers and molecular scaffolds. Vertebrate genomes contain 9-17 septin genes
      that encode both ubiquitous and tissue-specific septins. Expressed septins may
      assemble in various combinations through both heterotypic and homotypic G-domain
      interactions. However, little is known regarding assembly states of mammalian
      septins and mechanisms directing ordered assembly of individual septins into
      heteromeric units, which is the focus of this study. Our analysis of the septin
      system in cells lacking or overexpressing selected septins reveals
      interdependencies coinciding with previously described homology subgroups.
      Hydrodynamic and single-particle data show that individual septins exist solely
      in the context of stable six- to eight-subunit core heteromers, all of which
      contain SEPT2 and SEPT6 subgroup members and SEPT7, while heteromers comprising
      more than six subunits also contain SEPT9. The combined data suggest a generic
      model for how the temporal order of septin assembly is homology subgroup
      directed, which in turn determines the subunit arrangement of native heteromers.
      Because mammalian cells normally express multiple members and/or isoforms of some
      septin subgroups, our data also suggest that only a minor fraction of native
      heteromers are arranged as perfect palindromes.

PMID- 21737678
TI  - Microtubule assembly in meiotic extract requires glycogen.
AB  - The assembly of microtubules during mitosis requires many identified components,
      such as gamma-tubulin ring complex (gamma-TuRC), components of the Ran pathway
      (e.g., TPX2, HuRP, and Rae1), and XMAP215/chTOG. However, it is far from clear
      how these factors function together or whether more factors exist. In this study,
      we used biochemistry to attempt to identify active microtubule nucleation protein
      complexes from Xenopus meiotic egg extracts. Unexpectedly, we found both
      microtubule assembly and bipolar spindle assembly required glycogen, which acted
      both as a crowding agent and as metabolic source glucose. By also reconstituting
      microtubule assembly in clarified extracts, we showed microtubule assembly does
      not require ribosomes, mitochondria, or membranes. Our clarified extracts will
      provide a powerful tool for activity-based biochemical fractionations for
      microtubule assembly.

PMID- 21737679
TI  - Mannose-6-phosphate regulates destruction of lipid-linked oligosaccharides.
AB  - Mannose-6-phosphate (M6P) is an essential precursor for mannosyl glycoconjugates,
      including lipid-linked oligosaccharides (LLO; glucose(3)mannose(9)GlcNAc(2)-P-P
      dolichol) used for protein N-glycosylation. In permeabilized mammalian cells, M6P
      also causes specific LLO cleavage. However, the context and purpose of this
      paradoxical reaction are unknown. In this study, we used intact mouse embryonic
      fibroblasts to show that endoplasmic reticulum (ER) stress elevates M6P
      concentrations, leading to cleavage of the LLO pyrophosphate linkage with
      recovery of its lipid and lumenal glycan components. We demonstrate that this M6P
      originates from glycogen, with glycogenolysis activated by the kinase domain of
      the stress sensor IRE1-alpha. The apparent futility of M6P causing destruction of
      its LLO product was resolved by experiments with another stress sensor, PKR-like
      ER kinase (PERK), which attenuates translation. PERK's reduction of N
      glycoprotein synthesis (which consumes LLOs) stabilized steady-state LLO levels
      despite continuous LLO destruction. However, infection with herpes simplex virus
      1, an N-glycoprotein-bearing pathogen that impairs PERK signaling, not only
      caused LLO destruction but depleted LLO levels as well. In conclusion, the common
      metabolite M6P is also part of a novel mammalian stress-signaling pathway,
      responding to viral stress by depleting host LLOs required for N-glycosylation of
      virus-associated polypeptides. Apparently conserved throughout evolution, LLO
      destruction may be a response to a variety of environmental stresses.

PMID- 21737680
TI  - Translocation channel gating kinetics balances protein translocation efficiency
      with signal sequence recognition fidelity.
AB  - The transition between the closed and open conformations of the Sec61 complex
      permits nascent protein insertion into the translocation channel. A critical
      event in this structural transition is the opening of the lateral translocon gate
      that is formed by four transmembrane (TM) spans (TM2, TM3, TM7, and TM8 in
      Sec61p) to expose the signal sequence-binding site. To gain mechanistic insight
      into lateral gate opening, mutations were introduced into a lumenal loop (L7)
      that connects TM7 and TM8. The sec61 L7 mutants were found to have defects in
      both the posttranslational and cotranslational translocation pathways due to a
      kinetic delay in channel gating. The translocation defect caused by L7 mutations
      could be suppressed by the prl class of sec61 alleles, which reduce the fidelity
      of signal sequence recognition. The prl mutants are proposed to act by
      destabilizing the closed conformation of the translocation channel. Our results
      indicate that the equilibrium between the open and closed conformations of the
      protein translocation channel maintains a balance between translocation activity
      and signal sequence recognition fidelity.

PMID- 21737681
TI  - Anillin promotes astral microtubule-directed cortical myosin polarization.
AB  - Assembly of a cytokinetic contractile ring is a form of cell polarization in
      which the equatorial cell cortex becomes differentiated from the polar regions.
      Microtubules direct cytokinetic polarization via the central spindle and astral
      microtubules. The mechanism of central spindle-directed furrow formation is
      reasonably well understood, but the aster-directed pathway is not. In aster
      directed furrowing, cytoskeletal factors accumulate to high levels at sites
      distal to the asters and at reduced levels at cortical sites near the asters. In
      this paper, we demonstrate that the cytoskeletal organizing protein anillin (ANI
      1) promotes the formation of an aster-directed furrow in Caenorhabditis elegans
      embryos. Microtubule-directed nonmuscle myosin II polarization is aberrant in
      embryos depleted of ANI-1. In contrast, microtubule-directed polarized ANI-1
      localization is largely unaffected by myosin II depletion. Consistent with a role
      in the induction of cortical asymmetry, ANI-1 also contributes to the
      polarization of arrested oocytes. Anillin has an evolutionarily conserved
      capacity to associate with microtubules, possibly providing an inhibitory
      mechanism to promote polarization of the cell cortex.

PMID- 21737682
TI  - Structural and functional analysis of the repressor complex in the Notch
      signaling pathway of Drosophila melanogaster.
AB  - In metazoans, the highly conserved Notch pathway drives cellular specification.
      On receptor activation, the intracellular domain of Notch assembles a
      transcriptional activator complex that includes the DNA-binding protein CSL, a
      composite of human C-promoter binding factor 1, Suppressor of Hairless of
      Drosophila melanogaster [Su(H)], and lin-12 and Glp-1 phenotype of Caenorhabditis
      elegans. In the absence of ligand, CSL represses Notch target genes. However,
      despite the structural similarity of CSL orthologues, repression appears largely
      diverse between organisms. Here we analyze the Notch repressor complex in
      Drosophila, consisting of the fly CSL protein, Su(H), and the corepressor
      Hairless, which recruits general repressor proteins. We show that the C-terminal
      domain of Su(H) is necessary and sufficient for forming a high-affinity complex
      with Hairless. Mutations in Su(H) that affect interactions with Notch and
      Mastermind have no effect on Hairless binding. Nonetheless, we demonstrate that
      Notch and Hairless compete for CSL in vitro and in cell culture. In addition, we
      identify a site in Hairless that is crucial for binding Su(H) and subsequently
      show that this Hairless mutant is strongly impaired, failing to properly assemble
      the repressor complex in vivo. Finally, we demonstrate Hairless-mediated
      inhibition of Notch signaling in a cell culture assay, which hints at a
      potentially similar repression mechanism in mammals that might be exploited for
      therapeutic purposes.

PMID- 21737683
TI  - Podosome rings generate forces that drive saltatory osteoclast migration.
AB  - Podosomes are dynamic, actin-containing adhesion structures that collectively
      self-organize as rings. In this study, we first show by observing osteoclasts
      plated on bead-seeded soft substrates that podosome assemblies, such as rings,
      are involved in tension forces. During the expansion of a podosome ring,
      substrate displacement is oriented outward, suggesting that podosomal structures
      push the substrate away. To further elucidate the function of forces generated by
      podosomes, we analyze osteoclast migration. Determining the centers of mass of
      the whole cell (G) and of actin (P), we demonstrate that osteoclasts migrate by
      "jumps" and that the trajectories of G and P are strongly correlated. The
      velocity of the center of mass as a function of time reveals that osteoclasts
      rapidly catch up with podosomal structures in a periodic pattern. We conclude
      that actin dynamics inside the cell are not only correlated with cell migration,
      but drive it.

PMID- 21737684
TI  - Mi-2/NuRD complex function is required for normal S phase progression and
      assembly of pericentric heterochromatin.
AB  - During chromosome duplication, it is essential to replicate not only the DNA
      sequence, but also the complex nucleoprotein structures of chromatin. Pericentric
      heterochromatin is critical for silencing repetitive elements and plays an
      essential structural role during mitosis. However, relatively little is
      understood about its assembly and maintenance during replication. The Mi2/NuRD
      chromatin remodeling complex tightly associates with actively replicating
      pericentric heterochromatin, suggesting a role in its assembly. Here we
      demonstrate that depletion of the catalytic ATPase subunit CHD4/Mi-2beta in cells
      with a dampened DNA damage response results in a slow-growth phenotype
      characterized by delayed progression through S phase. Furthermore, we observe
      defects in pericentric heterochromatin maintenance and assembly. Our data suggest
      that chromatin assembly defects are sensed by an ATM-dependent intra-S phase
      chromatin quality checkpoint, resulting in a temporal block to the transition
      from early to late S phase. These findings implicate Mi-2beta in the maintenance
      of chromatin structure and proper cell cycle progression.

PMID- 21737685
TI  - Kif18B interacts with EB1 and controls astral microtubule length during mitosis.
AB  - Regulation of microtubule (MT) dynamics is essential for proper spindle assembly
      and organization. Kinesin-8 family members are plus-end-directed motors that
      modulate plus-end MT dynamics by acting as MT depolymerases or as MT plus-end
      capping proteins. In this paper, we show that the human kinesin-8 Kif18B
      functions during mitosis to control astral MT organization. Kif18B is a MT plus
      tip-tracking protein that localizes to the nucleus in interphase and is enriched
      at astral MT plus ends during early mitosis. Knockdown of Kif18B caused spindle
      defects, resulting in an increased number and length of MTs. A yeast two-hybrid
      screen identified an interaction of the C-terminal domain of Kif18B with the plus
      end MT-binding protein EB1. EB1 knockdown disrupted Kif18B targeting to MT plus
      ends, indicating that EB1/Kif18B interaction is physiologically important. This
      interaction is direct, as the far C-terminal end of Kif18B is sufficient for
      binding to EB1 in vitro. Overexpression of this domain is sufficient for plus-end
      MT targeting in cells; however, targeting is enhanced by the motor domain, which
      cooperates with the tail to achieve proper Kif18B localization at MT plus ends.
      Our results suggest that Kif18B is a new MT dynamics regulatory protein that
      interacts with EB1 to control astral MT length.

PMID- 21737686
TI  - Ankrd2/ARPP is a novel Akt2 specific substrate and regulates myogenic
      differentiation upon cellular exposure to H(2)O(2).
AB  - Activation of Akt-mediated signaling pathways is crucial for survival,
      differentiation, and regeneration of muscle cells. A proteomic-based search for
      novel substrates of Akt was therefore undertaken in C(2)C(12) murine muscle cells
      exploiting protein characterization databases in combination with an anti-phospho
      Akt substrate antibody. A Scansite database search predicted Ankrd2 (Ankyrin
      repeat domain protein 2, also known as ARPP) as a novel substrate of Akt. In
      vitro and in vivo studies confirmed that Akt phosphorylates Ankrd2 at Ser-99.
      Moreover, by kinase assay with recombinant Akt1 and Akt2, as well as by single
      isoform silencing, we demonstrated that Ankrd2 is a specific substrate of Akt2.
      Ankrd2 is typically found in skeletal muscle cells, where it mediates the
      transcriptional response to stress conditions. In an attempt to investigate the
      physiological implications of Ankrd2 phosphorylation by Akt2, we found that
      oxidative stress induced by H(2)O(2) triggers this phosphorylation. Moreover, the
      forced expression of a phosphorylation-defective mutant form of Ankrd2 in
      C(2)C(12) myoblasts promoted a faster differentiation program, implicating Akt
      dependent phosphorylation at Ser-99 in the negative regulation of myogenesis in
      response to stress conditions.

PMID- 21737687
TI  - Nuclear lipid microdomains regulate nuclear vitamin D3 uptake and influence
      embryonic hippocampal cell differentiation.
AB  - Despite recent advances in the understanding of the role of 1,25-dihydroxyvitamin
      D(3) (1,25-(OH)(2)D(3)) in the CNS, the mechanism of action remains obscure. We
      demonstrate that some 1,25-(OH)(2)D(3) receptor (VDR) is localized in the cell
      nucleus in specialized microdomains enriched in sphingomyelin and cholesterol;
      the integrity of these microdomains is necessary for embryonic hippocampal cell
      differentiation. Sphingomyelinase (SMase) treatment reduces both VDR and labeled
      1,25-(OH)(2)D(3) content in nuclear microdomains. We have previously shown that
      HN9.10e embryonic hippocampal cells differentiate when incubated with 100 nM 1,25
      (OH)(2)D(3) in the presence of 10% fetal calf serum, while serum deprivation
      induces cell death. In this study, we have investigated whether conditions that
      alter lipid content of nuclear microdomains modify 1,25-(OH)(2)D(3)-induced
      differentiation. Serum deprivation activates SMase and modifies the composition
      of nuclear microdomains, which lose the 1,25-(OH)(2) vitamin D(3) receptor. The
      incubation of serum-deprived cells with 100 nM 1,25-(OH)(2)D(3) prevents
      differentiation. However, treatment with 400 nM 1,25-(OH)(2)D(3) during serum
      withdrawal increases the lipid content of the nuclear microdomains, allows the
      interaction of 1,25-(OH)(2)D(3) with its receptor, and results in
      differentiation. These results suggest the presence of VDR in nuclear
      microdomains is necessary for 1,25-(OH)(2)D(3)-induced differentiation in
      embryonic hippocampal cells.

PMID- 21737688
TI  - Yos9p assists in the degradation of certain nonglycosylated proteins from the
      endoplasmic reticulum.
AB  - The HRD ubiquitin ligase recognizes and ubiquitylates proteins of the endoplasmic
      reticulum that display structural defects. Here, we apply quantitative proteomics
      to characterize the substrate spectrum of the HRD complex. Among the identified
      substrates is Erg3p, a glycoprotein involved in sterol synthesis. We characterize
      Erg3p and demonstrate that the elimination of Erg3p requires Htm1p and Yos9p, two
      proteins that take part in the glycan-dependent turnover of aberrant proteins. We
      further show that the HRD ligase also mediates the breakdown of Erg3p and CPY*
      engineered to lack N-glycans. The degradation of these nonglycosylated substrates
      is enhanced by a mutant variant of Yos9p that has lost its affinity for
      oligosaccharides, indicating that Yos9p has a previously unrecognized role in the
      quality control of nonglycosylated proteins.

PMID- 21737689
TI  - The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting
      both at meiotic and postmeiotic stages.
AB  - Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate
      protein synthesis during germ cell development relies on RNA binding proteins
      that control the storage, stability, and translation of mRNAs in a tightly and
      temporally regulated manner. Here, we focused on the RNA binding protein
      Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a
      key regulator of posttranscriptional regulation in somatic cells but the function
      of which during gametogenesis has never been investigated. In this study, we have
      used conditional loss- and gain-of-function approaches to address this issue in
      mice. We show that targeted deletion of HuR specifically in germ cells leads to
      male but not female sterility. Mutant males are azoospermic because of the
      extensive death of spermatocytes at meiotic divisions and failure of spermatid
      elongation. The latter defect is also observed upon HuR overexpression. To
      elucidate further the molecular mechanisms underlying spermatogenesis defects in
      HuR-deleted and -overexpressing testes, we undertook a target gene approach and
      discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of
      spermatogenesis, was down-regulated in both situations. HuR specifically binds
      hspa2 mRNA and controls its expression at the translational level in germ cells.
      Our study provides the first genetic evidence of HuR involvement during
      spermatogenesis and reveals Hspa2 as a target for HuR.

PMID- 21737690
TI  - Regulation of cyclin-dependent kinase 4 translation through CUG-binding protein 1
      and microRNA-222 by polyamines.
AB  - The amino acid-derived polyamines are organic cations that are essential for
      growth in all mammalian cells, but their exact roles at the molecular level
      remain largely unknown. Here we provide evidence that polyamines promote the
      translation of cyclin-dependent kinase 4 (CDK4) by the action of CUG-binding
      protein 1 (CUGBP1) and microRNA-222 (miR-222) in intestinal epithelial cells.
      Both CUGBP1 and miR-222 were found to bind the CDK4 mRNA coding region and 3'
      untranslated region and repressed CDK4 translation synergistically. Depletion of
      cellular polyamines increased cytoplasmic CUGBP1 abundance and miR-222 levels,
      induced their associations with the CDK4 mRNA, and inhibited CDK4 translation,
      whereas increasing the levels of cellular polyamines decreased CDK4 mRNA
      interaction with CUGBP1 and miR-222, in turn inducing CDK4 expression. Polyamine
      deficient cells exhibited an increased colocalization of tagged CDK4 mRNA with
      processing bodies; this colocalization was abolished by silencing CUGBP1 and miR
      222. Together, our findings indicate that polyamine-regulated CUGBP1 and miR-222
      modulate CDK4 translation at least in part by altering the recruitment of CDK4
      mRNA to processing bodies.

PMID- 21737691
TI  - Calcium signals and calpain-dependent necrosis are essential for release of
      coxsackievirus B from polarized intestinal epithelial cells.
AB  - Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized
      epithelial cells lining the intestinal tract early in infection. Although the
      polarized epithelium functions as a protective barrier, this barrier is likely
      exploited by CVB to promote viral entry and subsequent egress. Here we show that,
      in contrast to nonpolarized cells, CVB-infected polarized intestinal Caco-2 cells
      undergo nonapoptotic necrotic cell death triggered by inositol 1,4,5
      trisphosphate receptor-dependent calcium release. We further show that CVB
      induced cellular necrosis depends on the Ca(2+)-activated protease calpain-2 and
      that this protease is involved in CVB-induced disruption of the junctional
      complex and rearrangements of the actin cytoskeleton. Our study illustrates the
      cell signaling pathways hijacked by CVB, and perhaps other viral pathogens, to
      promote their replication and spread in polarized cell types.

PMID- 21737692
TI  - Insights into EB1 structure and the role of its C-terminal domain for
      discriminating microtubule tips from the lattice.
AB  - End-binding proteins (EBs) comprise a conserved family of microtubule plus end
      tracking proteins. The concerted action of calponin homology (CH), linker, and C
      terminal domains of EBs is important for their autonomous microtubule tip
      tracking, regulation of microtubule dynamics, and recruitment of numerous
      partners to microtubule ends. Here we report the detailed structural and
      biochemical analysis of mammalian EBs. Small-angle X-ray scattering, electron
      microscopy, and chemical cross-linking in combination with mass spectrometry
      indicate that EBs are elongated molecules with two interacting CH domains, an
      arrangement reminiscent of that seen in other microtubule- and actin-binding
      proteins. Removal of the negatively charged C-terminal tail did not affect the
      overall conformation of EBs; however, it increased the dwell times of EBs on the
      microtubule lattice in microtubule tip-tracking reconstitution experiments. An
      even more stable association with the microtubule lattice was observed when the
      entire negatively charged C-terminal domain of EBs was replaced by a neutral
      coiled-coil motif. In contrast, the interaction of EBs with growing microtubule
      tips was not significantly affected by these C-terminal domain mutations. Our
      data indicate that long-range electrostatic repulsive interactions between the C
      terminus and the microtubule lattice drive the specificity of EBs for growing
      microtubule ends.

PMID- 21737693
TI  - StatBite. Multiple myeloma: five-year relative survival.

PMID- 21737694
TI  - Embryonic stem cell research moves slowly through appeals courts, cancer trials.

PMID- 21737695
TI  - Beyond ipilimumab: new approaches target the immunological synapse.

PMID- 21737696
TI  - Myeloma researchers gain genome, new targets, and new concerns.

PMID- 21737697
TI  - StatBite: Breast cancer incidence in the U.S. and Italy.

PMID- 21737698
TI  - Drosophila Sex lethal gene initiates female development in germline progenitors.
AB  - Sex determination in the Drosophila germ line is regulated by both the sex of the
      surrounding soma and cell-autonomous cues. How primordial germ cells (PGCs)
      initiate sexual development via cell-autonomous mechanisms is unclear. Here, we
      demonstrate that, in Drosophila, the Sex lethal (Sxl) gene acts autonomously in
      PGCs to induce female development. Sxl is transiently expressed in PGCs during
      their migration to the gonads; this expression, which was detected only in XX
      PGCs, is necessary for PGCs to assume a female fate. Ectopic expression of Sxl in
      XY PGCs was sufficient to induce them to enter oogenesis and produce functional
      eggs when transplanted into an XX host. Our data provide powerful evidence that
      Sxl initiates female germline fate during sexual development.

PMID- 21737699
TI  - Conservation. High value and long life--double jeopardy for tunas and billfishes.

PMID- 21737700
TI  - Herschel detects a massive dust reservoir in supernova 1987A.
AB  - We report far-infrared and submillimeter observations of supernova 1987A, the
      star whose explosion was observed on 23 February 1987 in the Large Magellanic
      Cloud, a galaxy located 160,000 light years away. The observations reveal the
      presence of a population of cold dust grains radiating with a temperature of
      about 17 to 23 kelvin at a rate of about 220 times the luminosity of the Sun. The
      intensity and spectral energy distribution of the emission suggest a dust mass of
      about 0.4 to 0.7 times the mass of the Sun. The radiation must originate from the
      supernova ejecta and requires the efficient precipitation of all refractory
      material into dust. Our observations imply that supernovae can produce the large
      dust masses detected in young galaxies at very high redshifts.

PMID- 21737701
TI  - CRASY: mass- or electron-correlated rotational alignment spectroscopy.
AB  - Rotational spectra have traditionally been measured without a concurrent means of
      differentiating the molecular constituents of the sample. Here, we present an all
      optical multipulse experiment that allows the correlated measurement of
      rotational and mass or photoelectron spectra by combining Fourier transform
      rotational coherence spectroscopy with resonance-enhanced multiphoton ionization.
      We demonstrate the power of this method with the determination of ground-state
      rotational constants and fragmentation channels for 10 different isotopes in a
      natural carbon disulfide sample. Three of the reported rotational constants were
      previously inaccessible by conventional spectroscopic techniques.

PMID- 21737702
TI  - A highly conserved neutralizing epitope on group 2 influenza A viruses.
AB  - Current flu vaccines provide only limited coverage against seasonal strains of
      influenza viruses. The identification of V(H)1-69 antibodies that broadly
      neutralize almost all influenza A group 1 viruses constituted a breakthrough in
      the influenza field. Here, we report the isolation and characterization of a
      human monoclonal antibody CR8020 with broad neutralizing activity against most
      group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The
      crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA)
      reveals a highly conserved epitope in the HA stalk distinct from the epitope
      recognized by the V(H)1-69 group 1 antibodies. Thus, a cocktail of two antibodies
      may be sufficient to neutralize most influenza A subtypes and, hence, enable
      development of a universal flu vaccine and broad-spectrum antibody therapies.

PMID- 21737703
TI  - Schema-dependent gene activation and memory encoding in neocortex.
AB  - When new learning occurs against the background of established prior knowledge,
      relevant new information can be assimilated into a schema and thereby expand the
      knowledge base. An animal model of this important component of memory
      consolidation reveals that systems memory consolidation can be very fast. In
      experiments with rats, we found that the hippocampal-dependent learning of new
      paired associates is associated with a striking up-regulation of immediate early
      genes in the prelimbic region of the medial prefrontal cortex, and that
      pharmacological interventions targeted at that area can prevent both new learning
      and the recall of remotely and even recently consolidated information. These
      findings challenge the concept of distinct fast (hippocampal) and slow (cortical)
      learning systems, and shed new light on the neural mechanisms of memory
      assimilation into schemas.

PMID- 21737704
TI  - Tranexamic acid reduces blood loss after off-pump coronary surgery: a
      prospective, randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Bleeding and the need for allogeneic transfusions are still problems
      after off-pump coronary artery bypass grafting (OPCAB) surgery. We therefore
      evaluated the effects of an antifibrinolytic, tranexamic acid, on postoperative
      bleeding and transfusion requirements in patients undergoing OPCAB surgery.
      METHODS: Two hundred thirty-one consecutive patients scheduled for elective OPCAB
      were enrolled in the study. Using a double-blind method, the patients were
      randomly assigned to receive either tranexamic acid (bolus 1 g before surgical
      incision followed by an infusion of 400 mg/h during surgery; n = 116) or a
      placebo (infusion equivalent volume of saline solution; n = 115). The primary
      outcome was 24-hour postoperative chest tube drainage. Allogeneic transfusion,
      mortality, major morbidities, and resource utilization were also recorded.
      RESULTS: In comparison with the placebo group, the patients receiving tranexamic
      acid had a significant reduction in chest tube drainage at 6 hours (270 +/- 118
      mL vs 416 +/- 179 mL, P < 0.001) and 24 hours (654 +/- 224 mL vs 891 +/- 295 mL,
      P < 0.001). There was also a significant reduction in allogeneic red blood cell
      transfusions (47 vs 31.9%, P = 0.019) and fresh frozen plasma (29.6% vs 17.2%, P
      = 0.027) transfusions. There were no differences in mortality, morbidity, and
      resource utilization between the 2 groups. CONCLUSIONS: Tranexamic acid reduces
      postoperative chest tube drainage and the requirement for allogeneic transfusion
      in off-pump coronary surgery.

PMID- 21737705
TI  - Cannabidiol prevents the development of cold and mechanical allodynia in
      paclitaxel-treated female C57Bl6 mice.
AB  - The taxane chemotherapeutic paclitaxel frequently produces peripheral neuropathy
      in humans. Rodent models to investigate mechanisms and treatments are largely
      restricted to male rats, whereas female mouse studies are lacking. We
      characterized a range of paclitaxel doses on cold and mechanical allodynia in
      male and female C57Bl/6 mice. Because the nonpsychoactive phytocannabinoid
      cannabidiol attenuates other forms of neuropathic pain, we assessed its effect on
      paclitaxel-induced allodynia. Paclitaxel produced allodynia that was largely dose
      independent and more robust in female mice, and this effect was prevented by
      treatment with cannabidiol. Our preliminary findings therefore indicate that
      cannabidiol may prevent the development of paclitaxel-induced allodynia in mice
      and therefore be effective at preventing dose-limiting paclitaxel-induced
      peripheral neuropathy in humans.

PMID- 21737706
TI  - The impact of perioperative catastrophes on anesthesiologists: results of a
      national survey.
AB  - BACKGROUND: Most anesthesiologists will experience at least one perioperative
      catastrophe over the course of their careers. Very little, however, is known
      about the emotional impact of these events and their effects on both immediate
      and long-term ability to provide care. In this study, we examined the incidence
      of perioperative catastrophes and the impact of these outcomes on American
      anesthesiologists. METHODS: We sent a self-administered postal survey to 1200
      randomly selected members of the American Society of Anesthesiologists.
      Participants were sent an advance letter, up to 2 copies of the survey, up to 2
      reminder postcards, and a small cash incentive. Six hundred fifty-nine physicians
      (56%) completed the survey. RESULTS: Eighty-four percent of respondents had been
      involved in at least one unanticipated death or serious injury of a perioperative
      patient over the course of his/her career. Queried about the emotional impact of
      a "most memorable" perioperative catastrophe, >70% experienced guilt, anxiety,
      and reliving of the event with 88% requiring time to recover emotionally from the
      event and 19% acknowledging having never fully recovered. Twelve percent
      considered a career change. Sixty-seven percent of respondents believed that
      their ability to provide patient care was compromised in the first 4 hours
      subsequent to the event, but only 7% were given time off. CONCLUSION: A
      perioperative catastrophe may have a profound and lasting emotional impact on the
      anesthesiologist involved and may affect his or her ability to provide patient
      care in the aftermath of such events.

PMID- 21737707
TI  - A threat to medical innovation.

PMID- 21737712
TI  - FDA. Once on 'fast track,' avastin now derailed.

PMID- 21737713
TI  - China. Foreign researchers begin to make their mark.

PMID- 21737714
TI  - Newsmaker interview: Debora Zarin. Unseen world of clinical trials emerges from
      U.S. database. Interview by Eliot Marshall.

PMID- 21737715
TI  - Ecology. Cash advance, new approach aim to relaunch Biosphere 2.

PMID- 21737716
TI  - Synthetic biology. DARPA offers $30 million to jump-start cellular factories.

PMID- 21737717
TI  - Nuclear waste. Waste panel expected to back interim storage.

PMID- 21737718
TI  - Radioactive waste disposal. Light at the end of the radwaste disposal tunnel
      could be real.

PMID- 21737719
TI  - Japan disaster. Picking up the pieces at ravaged Tohoku University.

PMID- 21737720
TI  - Japan disaster. Facilities plot research revival.

PMID- 21737721
TI  - Manufacturing decline yields drug shortages.

PMID- 21737723
TI  - NSF's struggle to articulate relevance.

PMID- 21737722
TI  - Seeds of change for restoration ecology.

PMID- 21737724
TI  - Astrophysics. A dark age for space astronomy?

PMID- 21737726
TI  - Physics. Precision, not power.

PMID- 21737725
TI  - Medicine. Lipases in cachexia.

PMID- 21737727
TI  - Applied physics. A critical point for turbulence.

PMID- 21737728
TI  - Evolution. Sex, death, and the Red Queen.

PMID- 21737729
TI  - Galaxy evolution. A universe of galaxies. Introduction.

PMID- 21737730
TI  - Galaxy evolution. Milky way researchers' home away from home.

PMID- 21737731
TI  - Galaxy evolution. Galaxy zoo volunteers share pain and glory of research.

PMID- 21737732
TI  - Galaxy evolution. Galactic paleontology.
AB  - Individual low-mass stars have very long lives, comparable to the age of the
      universe, and can thus be used to probe ancient star formation. At present, such
      stars can be identified and studied only in the Milky Way and in the very closest
      of our neighboring galaxies, which are predominantly small dwarf galaxies. These
      nearby ancient stars are a fossil record that can provide detailed information
      about the physical processes that dominated the epoch of galaxy formation and
      subsequent evolution.

PMID- 21737733
TI  - The cosmic history of star formation.
AB  - Major advances in observational astronomy over the past 20 years have
      revolutionized our view of cosmic history, transforming our understanding of how
      the hot, smooth, early universe evolved into the complex and beautiful universe
      of stars and galaxies in which we now live. I describe how astronomers have used
      a range of complementary techniques to map out the rise and fall of star
      formation over 95% of cosmic time, back to the current observational frontier
      only ~500 million years after the Big Bang.

PMID- 21737734
TI  - The coevolution of galaxies and supermassive black holes: a local perspective.
AB  - One of the most fascinating discoveries in the past decade was that galaxies
      typically contain a centrally located black hole with a mass that is millions or
      even billions of times that of the Sun. There is now compelling evidence that we
      cannot understand how galaxies formed and evolved without understanding the life
      cycles of these supermassive black holes (and vice versa). We summarize the
      current understanding of this coevolution of galaxies and supermassive black
      holes (based largely on observations of the local, present-day universe) and
      describe prospects for the future.

PMID- 21737735
TI  - Glycolytic oscillations and limits on robust efficiency.
AB  - Both engineering and evolution are constrained by trade-offs between efficiency
      and robustness, but theory that formalizes this fact is limited. For a simple two
      state model of glycolysis, we explicitly derive analytic equations for hard trade
      offs between robustness and efficiency with oscillations as an inevitable side
      effect. The model describes how the trade-offs arise from individual parameters,
      including the interplay of feedback control with autocatalysis of network
      products necessary to power and catalyze intermediate reactions. We then use
      control theory to prove that the essential features of these hard trade-off
      "laws" are universal and fundamental, in that they depend minimally on the
      details of this system and generalize to the robust efficiency of any
      autocatalytic network. The theory also suggests worst-case conditions that are
      consistent with initial experiments.

PMID- 21737736
TI  - The onset of turbulence in pipe flow.
AB  - Shear flows undergo a sudden transition from laminar to turbulent motion as the
      velocity increases, and the onset of turbulence radically changes transport
      efficiency and mixing properties. Even for the well-studied case of pipe flow, it
      has not been possible to determine at what Reynolds number the motion will be
      either persistently turbulent or ultimately laminar. We show that in pipes,
      turbulence that is transient at low Reynolds numbers becomes sustained at a
      distinct critical point. Through extensive experiments and computer simulations,
      we were able to identify and characterize the processes ultimately responsible
      for sustaining turbulence. In contrast to the classical Landau-Ruelle-Takens view
      that turbulence arises from an increase in the temporal complexity of fluid
      motion, here, spatial proliferation of chaotic domains is the decisive process
      and intrinsic to the nature of fluid turbulence.

PMID- 21737737
TI  - Frequency metrology in quantum degenerate helium: direct measurement of the 2 3S1
      --> 2 1S0 transition.
AB  - Precision spectroscopy of simple atomic systems has refined our understanding of
      the fundamental laws of quantum physics. In particular, helium spectroscopy has
      played a crucial role in describing two-electron interactions, determining the
      fine-structure constant and extracting the size of the helium nucleus. Here we
      present a measurement of the doubly forbidden 1557-nanometer transition
      connecting the two metastable states of helium (the lowest energy triplet state 2
      (3)S(1) and first excited singlet state 2 (1)S(0)), for which quantum
      electrodynamic and nuclear size effects are very strong. This transition is
      weaker by 14 orders of magnitude than the most predominantly measured transition
      in helium. Ultracold, submicrokelvin, fermionic (3)He and bosonic (4)He atoms are
      used to obtain a precision of 8 * 10(-12), providing a stringent test of two
      electron quantum electrodynamic theory and of nuclear few-body theory.

PMID- 21737738
TI  - Observation of transient structural-transformation dynamics in a Cu2S nanorod.
AB  - The study of first-order structural transformations has been of great interest to
      scientists in many disciplines. Expectations from phase-transition theory are
      that the system fluctuates between two equilibrium structures near the transition
      point and that the region of transition broadens in small crystals. We report the
      direct observation of structural fluctuations within a single nanocrystal using
      transmission electron microscopy. We observed trajectories of structural
      transformations in individual nanocrystals with atomic resolution, which reveal
      details of the fluctuation dynamics, including nucleation, phase propagation, and
      pinning of structural domains by defects. Such observations provide crucial
      insight for the understanding of microscopic pathways of phase transitions.

PMID- 21737739
TI  - Running with the Red Queen: host-parasite coevolution selects for biparental sex.
AB  - Most organisms reproduce through outcrossing, even though it comes with
      substantial costs. The Red Queen hypothesis proposes that selection from
      coevolving pathogens facilitates the persistence of outcrossing despite these
      costs. We used experimental coevolution to test the Red Queen hypothesis and
      found that coevolution with a bacterial pathogen (Serratia marcescens) resulted
      in significantly more outcrossing in mixed mating experimental populations of the
      nematode Caenorhabditis elegans. Furthermore, we found that coevolution with the
      pathogen rapidly drove obligately selfing populations to extinction, whereas
      outcrossing populations persisted through reciprocal coevolution. Thus,
      consistent with the Red Queen hypothesis, coevolving pathogens can select for
      biparental sex.

PMID- 21737740
TI  - Isolation of single human hematopoietic stem cells capable of long-term
      multilineage engraftment.
AB  - Lifelong blood cell production is dependent on rare hematopoietic stem cells
      (HSCs) to perpetually replenish mature cells via a series of lineage-restricted
      intermediates. Investigating the molecular state of HSCs is contingent on the
      ability to purify HSCs away from transiently engrafting cells. We demonstrated
      that human HSCs remain infrequent, using current purification strategies based on
      Thy1 (CD90) expression. By tracking the expression of several adhesion molecules
      in HSC-enriched subsets, we revealed CD49f as a specific HSC marker. Single
      CD49f(+) cells were highly efficient in generating long-term multilineage grafts,
      and the loss of CD49f expression identified transiently engrafting multipotent
      progenitors (MPPs). The demarcation of human HSCs and MPPs will enable the
      investigation of the molecular determinants of HSCs, with a goal of developing
      stem cell-based therapeutics.

PMID- 21737741
TI  - A pericyte origin of spinal cord scar tissue.
AB  - There is limited regeneration of lost tissue after central nervous system injury,
      and the lesion is sealed with a scar. The role of the scar, which often is
      referred to as the glial scar because of its abundance of astrocytes, is complex
      and has been discussed for more than a century. Here we show that a specific
      pericyte subtype gives rise to scar-forming stromal cells, which outnumber
      astrocytes, in the injured spinal cord. Blocking the generation of progeny by
      this pericyte subtype results in failure to seal the injured tissue. The
      formation of connective tissue is common to many injuries and pathologies, and
      here we demonstrate a cellular origin of fibrosis.

PMID- 21737742
TI  - TSH receptor function is required for normal thyroid differentiation in
      zebrafish.
AB  - TSH is the primary physiological regulator of thyroid gland function. The effects
      of TSH on thyroid cells are mediated via activation of its membrane receptor [TSH
      receptor (TSHR)]. In this study, we examined functional thyroid differentiation
      in zebrafish and characterized the role of TSHR signaling during thyroid
      organogenesis. Cloning of a cDNA encoding zebrafish Tshr showed conservation of
      primary structure and functional properties between zebrafish and mammalian TSHR.
      In situ hybridization confirmed that the thyroid is the major site of tshr
      expression during zebrafish development. In addition, we identified tpo, iyd,
      duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal
      analyses of differentiation marker expression demonstrated the induction of an
      early thyroid differentiation program along with thyroid budding, followed by a
      delayed onset of duox and duoxa expression coincident with thyroid hormone
      synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for
      the first time a thyroid-enriched expression of cell death regulators of the B
      cell lymphoma 2 family during early thyroid morphogenesis. Knockdown of tshr
      function by morpholino microinjection into embryos did not affect early thyroid
      morphogenesis but caused defects in later functional differentiation. The thyroid
      phenotype observed in tshr morphants at later stages comprised a reduction in
      number and size of functional follicles, down-regulation of differentiation
      markers, as well as reduced thyroid transcription factor expression. A comparison
      of our results with phenotypes observed in mouse models of defective TSHR and
      cAMP signaling highlights the value of zebrafish as a model to enhance the
      understanding of functional differentiation in the vertebrate thyroid.

PMID- 21737743
TI  - Olfaction is a chemical sense, not a spectral sense.

PMID- 21737745
TI  - Avoiding disastrous climate change is possible but not inevitable.

PMID- 21737744
TI  - Oscillatory patterns in temporal lobe reveal context reinstatement during memory
      search.
AB  - Psychological theories of memory posit that when people recall a past event, they
      not only recover the features of the event itself, but also recover information
      associated with other events that occurred nearby in time. The events surrounding
      a target event, and the thoughts they evoke, may be considered to represent a
      context for the target event, helping to distinguish that event from similar
      events experienced at different times. The ability to reinstate this contextual
      information during memory search has been considered a hallmark of episodic, or
      event-based, memory. We sought to determine whether context reinstatement may be
      observed in electrical signals recorded from the human brain during episodic
      recall. Analyzing electrocorticographic recordings taken as 69 neurosurgical
      patients studied and recalled lists of words, we uncovered a neural signature of
      context reinstatement. Upon recalling a studied item, we found that the recorded
      patterns of brain activity were not only similar to the patterns observed when
      the item was studied, but were also similar to the patterns observed during study
      of neighboring list items, with similarity decreasing reliably with positional
      distance. The degree to which individual patients displayed this neural signature
      of context reinstatement was correlated with their tendency to recall neighboring
      list items successively. These effects were particularly strong in temporal lobe
      recordings. Our findings show that recalling a past event evokes a neural
      signature of the temporal context in which the event occurred, thus pointing to a
      neural basis for episodic memory.

PMID- 21737746
TI  - Inside insight to membrane fusion.

PMID- 21737747
TI  - An ATP-binding cassette subfamily G full transporter is essential for the
      retention of leaf water in both wild barley and rice.
AB  - Land plants have developed a cuticle preventing uncontrolled water loss. Here we
      report that an ATP-binding cassette (ABC) subfamily G (ABCG) full transporter is
      required for leaf water conservation in both wild barley and rice. A spontaneous
      mutation, eibi1.b, in wild barley has a low capacity to retain leaf water, a
      phenotype associated with reduced cutin deposition and a thin cuticle. Map-based
      cloning revealed that Eibi1 encodes an HvABCG31 full transporter. The gene was
      highly expressed in the elongation zone of a growing leaf (the site of cutin
      synthesis), and its gene product also was localized in developing, but not in
      mature tissue. A de novo wild barley mutant named "eibi1.c," along with two
      transposon insertion lines of rice mutated in the ortholog of HvABCG31 also were
      unable to restrict water loss from detached leaves. HvABCG31 is hypothesized to
      function as a transporter involved in cutin formation. Homologs of HvABCG31 were
      found in green algae, moss, and lycopods, indicating that this full transporter
      is highly conserved in the evolution of land plants.

PMID- 21737748
TI  - Genome-wide analysis reveals conserved and divergent features of Notch1/RBPJ
      binding in human and murine T-lymphoblastic leukemia cells.
AB  - Notch1 regulates gene expression by associating with the DNA-binding factor RBPJ
      and is oncogenic in murine and human T-cell progenitors. Using ChIP-Seq, we find
      that in human and murine T-lymphoblastic leukemia (TLL) genomes Notch1 binds
      preferentially to promoters, to RBPJ binding sites, and near imputed ZNF143, ETS,
      and RUNX sites. ChIP-Seq confirmed that ZNF143 binds to ~40% of Notch1 sites.
      Notch1/ZNF143 sites are characterized by high Notch1 and ZNF143 signals, frequent
      cobinding of RBPJ (generally through sites embedded within ZNF143 motifs), strong
      promoter bias, and relatively low mean levels of activating chromatin marks. RBPJ
      and ZNF143 binding to DNA is mutually exclusive in vitro, suggesting RBPJ/Notch1
      and ZNF143 complexes exchange on these sites in cells. K-means clustering of
      Notch1 binding sites and associated motifs identified conserved Notch1-RUNX,
      Notch1-ETS, Notch1-RBPJ, Notch1-ZNF143, and Notch1-ZNF143-ETS clusters with
      different genomic distributions and levels of chromatin marks. Although Notch1
      binds mainly to gene promoters, ~75% of direct target genes lack promoter binding
      and are presumably regulated by enhancers, which were identified near MYC, DTX1,
      IGF1R, IL7R, and the GIMAP cluster. Human and murine TLL genomes also have many
      sites that bind only RBPJ. Murine RBPJ-only sites are highly enriched for imputed
      REST (a DNA-binding transcriptional repressor) sites, whereas human RPBJ-only
      sites lack REST motifs and are more highly enriched for imputed CREB sites. Thus,
      there is a conserved network of cis-regulatory factors that interacts with Notch1
      to regulate gene expression in TLL cells, as well as unique classes of divergent
      RBPJ-only sites that also likely regulate transcription.

PMID- 21737749
TI  - Derepression of ethylene-stabilized transcription factors (EIN3/EIL1) mediates
      jasmonate and ethylene signaling synergy in Arabidopsis.
AB  - Jasmonate (JA) and ethylene (ET) are two major plant hormones that
      synergistically regulate plant development and tolerance to necrotrophic fungi.
      Both JA and ET induce the expression of several pathogenesis-related genes, while
      blocking either signaling pathway abolishes the induction of these genes by JA
      and ET alone or in combination. However, the molecular basis of JA/ET coaction
      and signaling interdependency is largely unknown. Here, we report that two
      Arabidopsis ET-stabilized transcription factors (EIN3 and EIL1) integrate ET and
      JA signaling in the regulation of gene expression, root development, and
      necrotrophic pathogen defense. Further studies reveal that JA enhances the
      transcriptional activity of EIN3/EIL1 by removal of JA-Zim domain (JAZ) proteins,
      which physically interact with and repress EIN3/EIL1. In addition, we find that
      JAZ proteins recruit an RPD3-type histone deacetylase (HDA6) as a corepressor
      that modulates histone acetylation, represses EIN3/EIL1-dependent transcription,
      and inhibits JA signaling. Our studies identify EIN3/EIL1 as a key integration
      node whose activation requires both JA and ET signaling, and illustrate
      transcriptional derepression as a common mechanism to integrate diverse signaling
      pathways in the regulation of plant development and defense.

PMID- 21737750
TI  - Maps of protein structure space reveal a fundamental relationship between protein
      structure and function.
AB  - To study the protein structure-function relationship, we propose a method to
      efficiently create three-dimensional maps of structure space using a very large
      dataset of > 30,000 Structural Classification of Proteins (SCOP) domains. In our
      maps, each domain is represented by a point, and the distance between any two
      points approximates the structural distance between their corresponding domains.
      We use these maps to study the spatial distributions of properties of proteins,
      and in particular those of local vicinities in structure space such as structural
      density and functional diversity. These maps provide a unique broad view of
      protein space and thus reveal previously undescribed fundamental properties
      thereof. At the same time, the maps are consistent with previous knowledge (e.g.,
      domains cluster by their SCOP class) and organize in a unified, coherent
      representation previous observation concerning specific protein folds. To
      investigate the function-structure relationship, we measure the functional
      diversity (using the Gene Ontology controlled vocabulary) in local structural
      vicinities. Our most striking finding is that functional diversity varies
      considerably across structure space: The space has a highly diverse region, and
      diversity abates when moving away from it. Interestingly, the domains in this
      region are mostly alpha/beta structures, which are known to be the most ancient
      proteins. We believe that our unique perspective of structure space will open
      previously undescribed ways of studying proteins, their evolution, and the
      relationship between their structure and function.

PMID- 21737751
TI  - Dispersed disease-causing neomorphic mutations on a single protein promote the
      same localized conformational opening.
AB  - The question of how dispersed mutations in one protein engender the same gain-of
      function phenotype is of great interest. Here we focus on mutations in glycyl
      tRNA synthetase (GlyRS) that cause an axonal form of Charcot-Marie-Tooth (CMT)
      diseases, the most common hereditary peripheral neuropathies. Because the disease
      phenotype is dominant, and not correlated with defects in the role of GlyRS in
      protein synthesis, the mutant proteins are considered to be neomorphs that gain
      new functions from altered protein structure. Given that previous crystal
      structures showed little conformational difference between dimeric wild-type and
      CMT-causing mutant GlyRSs, the mutant proteins were investigated in solution by
      hydrogen-deuterium exchange (monitored by mass spectrometry) and small-angle X
      ray scattering to uncover structural changes that could be suppressed by crystal
      packing interactions. Significantly, each of five spatially dispersed mutations
      induced the same conformational opening of a consensus area that is mostly buried
      in the wild-type protein. The identified neomorphic surface is thus a candidate
      for making CMT-associated pathological interactions, and a target for disease
      correction. Additional result showed that a helix-turn-helix WHEP domain that was
      appended to GlyRS in metazoans can regulate the neomorphic structural change, and
      that the gain of function of the CMT mutants might be due to the loss of function
      of the WHEP domain as a regulator. Overall, the results demonstrate how spatially
      dispersed and seemingly unrelated mutations can perpetrate the same localized
      effect on a protein.

PMID- 21737752
TI  - Structural basis for RNA 3'-end recognition by Hfq.
AB  - The homohexameric (L)Sm protein Hfq is a central mediator of small RNA-based gene
      regulation in bacteria. Hfq recognizes small regulatory RNAs (sRNAs)
      specifically, despite their structural diversity. This specificity could not be
      explained by previously described RNA-binding modes of Hfq. Here we present a
      distinct and preferred mode of Hfq-RNA interaction that involves the direct
      recognition of a uridine-rich RNA 3' end. This feature is common in bacterial RNA
      transcripts as a consequence of Rho-independent transcription termination and
      hence likely contributes significantly to the general recognition of sRNAs by
      Hfq. Isothermal titration calorimetry shows nanomolar affinity between Salmonella
      typhimurium Hfq and a hexauridine substrate. We determined a crystal structure of
      the complex that reveals a constricted RNA backbone conformation in the proximal
      RNA-binding site of Hfq, allowing for a direct protein contact of the 3' hydroxyl
      group. A free 3' hydroxyl group is crucial for the high-affinity interaction with
      Hfq also in the context of a full-length sRNA substrate, RybB. The capacity of
      Hfq to occupy and sequester the RNA 3' end has important implications for the
      mechanisms by which Hfq is thought to affect sRNA stability, turnover, and
      regulation.

PMID- 21737753
TI  - Chronic AMP-kinase activation with AICAR reduces adiposity by remodeling
      adipocyte metabolism and increasing leptin sensitivity.
AB  - This study investigated the effect of chronic AMP-kinase (AMPK) activation with 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on white adipose
      tissue (WAT) metabolism and the implications for visceral (VC) and subcutaneous
      (SC) adiposity, whole body-energy homeostasis, and hypothalamic leptin
      sensitivity. Male Wistar rats received daily single intraperitoneal injections of
      either saline or AICAR (0.7g/kg body weight) for 4 and 8 weeks and were pair-fed
      throughout the study. AICAR-treated rats had reduced adiposity with increased
      mitochondrial density in VC and SC fat pads, which was accompanied by reduced
      circulating leptin and time-dependent and depot-specific regulation of AMPK
      phosphorylation and FA oxidation. Interestingly, the anorectic effect to
      exogenous leptin was more pronounced in AICAR-treated animals than controls. This
      corresponded to reductions in hypothalamic AMPK phosphorylation and suppressor of
      cytokine signaling 3 content, whereas signal transducer and activator of
      transcription 3 phosphorylation was either unchanged or increased at 4 and 8
      weeks in AICAR-treated rats. Ambulatory activity and whole-body energy
      expenditure (EE) were also increased with AICAR treatment. Altogether, chronic
      AICAR-induced AMPK activation increased WAT oxidative machinery, whole-body EE,
      and hypothalamic leptin sensitivity. This led to significant reductions in VC and
      SC adiposity without inducing energy-sparing mechanisms that oppose long-term fat
      loss.

PMID- 21737754
TI  - Quantification of liver fat in mice: comparing dual-echo Dixon imaging, chemical
      shift imaging, and 1H-MR spectroscopy.
AB  - We evaluated dual-echo Dixon in-phase and out-of-phase (IP-OP), chemical shift
      imaging (CSI), and (1)H MRS (hydrogen MR spectroscopy) in estimating fat content
      (FC) in phantoms and in livers of mice. Phantoms were made according to the
      volume percentage of fat ranging from 0% to 100%. The three MR methods were
      performed to measure FC in phantoms and in livers of obese leptin-deficient
      (ob/ob), human BSCL2/seipin gene knockout (SKO), and wild-type (WT) mice. The
      results were compared with known FC in phantoms and to a reference standard from
      mice by histological semiautomatic vacuole segmentation (HIS-S) procedure and
      liver lipid (LL) chemical analysis. In phantoms, CSI underestimated FC from 50%
      to 100%, to a lesser extent than IP-OP. In vivo, liver FC in ob/ob and SKO mice
      measured by the three MR methods were all significantly higher than that in WT
      mice. Liver FC measured by IP-OP were significantly lower than that measured by
      CSI and MRS, with no significant difference between CSI and MRS. CSI and MRS
      showed a linear correlation with LL analysis and with each other. IP-OP
      underestimated FC, whereas CSI and MRS were more accurate for quantifying FC in
      both phantoms and liver. CSI and MRS have the potential to replace HIS-S and LL
      analysis in longitudinal studies.

PMID- 21737755
TI  - In this issue: testing characteristics of patient-centered medical homes, patient
      self-care, predicting outcomes, and practical clinical information.

PMID- 21737756
TI  - Content usage and the most frequently read articles in 2010.

PMID- 21737757
TI  - Guest family physician commentaries.

PMID- 21737758
TI  - Increasing timely and available prenatal studies by electronic health records.
AB  - BACKGROUND: The government is encouraging the adoption of electronic medical
      records (EMRs). There is little information about using EMRs in the obstetric
      literature and none about using them in family medicine residencies. Our purpose
      was to assess if using an EMR was associated with improvement in the ordering and
      availability of prenatal tests. METHODS: A retrospective chart review comparing
      the rate at which prenatal laboratory values were present on the chart, ordered
      on time, and recorded on a prenatal flow sheet. RESULTS: Comparison of charts
      before and after implementation of an EMR showed statistically significant
      improvement in the percent of patients with all first trimester (87.5% vs 96.0%;
      P=.0025), quadruple screening tests (91.1% vs 98.1%; P=.012), and second
      trimester screening results (93.5% vs 100%; P=.044) in their charts; first
      trimester laboratory tests (91.6% vs 99.5%; P=.001) and second trimester
      ultrasounds (90.9% vs 97.3%; P=.027) being ordered on time; and first trimester
      results (88.2% vs 95.5%; P=.009), quad screen results (93.1% vs 98.0%; P=.0495),
      and second trimester ultrasounds (93.5% vs 100%; P=.003) being recorded on the
      American Congress of Obstetricians and Gynecologists flow sheet. CONCLUSION:
      Adopting an EMR was associated with an improved rate at which prenatal tests were
      ordered on time, present on the chart, and recorded on a prenatal flow sheet.

PMID- 21737759
TI  - Preventive service gains from first contact access in the primary care home.
AB  - BACKGROUND: The patient-centered medical home (PCMH) concept recently has
      garnered national attention as a means of improving the quality of primary care.
      Preventive services are one area in which the use of a PCMH is hoped to achieve
      gains, though there has been limited exploration of PCMH characteristics that can
      assist with practice redesign. The purpose of this study was to examine whether
      first-contact access characteristics of a medical home (eg, availability of
      appointments or advice by telephone) confer additional benefit in the receipt of
      preventive services for individuals who already have a longitudinal relationship
      with a primary care physician at a site of care. METHODS: This was a secondary
      analysis examining data from 5507 insured adults with a usual physician who
      participated in the 2003 to 2006 round of the Wisconsin Longitudinal Study. Using
      logistic regression, we calculated the odds of receiving each preventive service,
      comparing individuals who had first-contact access with those without first
      contact access. RESULTS: Eighteen percent of the sample received care with first
      contact access. In multivariable analyses, after adjustment, individuals who had
      first-contact access had higher odds of having received a prostate examination
      (odds ratio [OR], 1.62; 95% CI, 1.20-2.18), a flu shot (OR, 1.36; 95% CI, 1.01
      1.82), and a cholesterol test (OR, 1.36; 95% CI, 1.01-1.82) during the past year.
      There was no significant difference in receipt of mammograms (OR, 1.23; 95% CI,
      0.94-1.61). CONCLUSIONS: In the primary care home, first-contact accessibility
      adds benefit, beyond continuity of care with a physician, in improving receipt of
      preventive services. Amid increasing primary care demands and finite resources
      available to translate the PCMH into clinic settings, there is a need for further
      studies of the interplay between specific PCMH principles and how they perform in
      practice.

PMID- 21737760
TI  - How eight primary care practices initiated and maintained quality monitoring and
      reporting.
AB  - BACKGROUND: Primary care medical practices increasingly are asked by payers,
      employers, and government agencies to report quality data, but the process of
      doing so is not well delineated. METHODS: Providers and office staff in a diverse
      sample of eight primary care practices in North Carolina comprised this study
      population. Interviews were conducted and self-administered questionnaires were
      disseminated in practices that were successfully reporting data to one or more of
      4 reporting programs. Our measures included responses to open-ended and Likert
      scale questions about experiences and potential facilitators and barriers, as
      well as subscales of the Practice Assessment tool and the Culture of Group
      Practices instrument. RESULTS: Study practices had stronger change histories,
      higher information and quality emphases, and lower business emphases than
      historical comparison practices. Motivation to participate, a leader who
      catalyzes the process, and establishment of new systems characterized successful
      practices. Staff time, information technology challenges, and resistance from
      some providers were common barriers. Practices achieve a sustainability state
      when numerous barriers have been successfully overcome and tangible results
      achieved from the process. CONCLUSIONS: Implementing and sustaining quality
      reporting requires a complex set of motivators, facilitators, and strategies to
      overcome inherent barriers that can present themselves in practices that seek to
      implement changes in this direction.

PMID- 21737761
TI  - What keeps patients from adhering to a home blood pressure program?
AB  - BACKGROUND: Home blood pressure monitoring (HBPM) predicts cardiovascular risk
      and increases hypertension control. Non-participation in HBPM is prevalent and
      decreases the potential benefit. METHODS: Telephone surveys were conducted with a
      random quota sample of non-participants in a HBPM program, which supplied a
      complimentary automated blood pressure cuff and utilized a centralized reporting
      system. Questioning assessed use of monitors, perceived benefit, communication
      with providers, and barriers. RESULTS: There were 320 completed surveys (response
      rate 53%). Of non-participants, 70.2% still used HBPM cuffs and 58% communicated
      values to providers. Spanish-speakers were 4.4 times more likely to not use cuffs
      (95% CI, 2.22-8.885). Barriers to participation were largely personal
      (forgetting, not having time, or self-described laziness). Reasons for not
      communicating readings with providers were largely clinic factors (no doctor
      visit, doctor didn't ask, thinking doctor wouldn't care). Lack of knowledge of
      HBPM and program design also contributed. After being surveyed, patients were
      over three times more likely to use the central reporting system. DISCUSSION:
      Most non-participants still used HBPM and communicated values to providers,
      suggesting many "drop-outs" may still receive clinical benefit. However, much
      valuable information is not utilized. Future programs should focus on reminder
      systems, patient motivation, education, and minimizing time involvement.

PMID- 21737762
TI  - How much time do adults spend on health-related self-care? Results from the
      American time use survey.
AB  - BACKGROUND: The amount of time individuals spend on health-related self-care is
      not known. OBJECTIVE: The aim of this study was to describe how much time
      American adults reported spending on health-related self-care (eg, taking
      insulin, dressing a wound). METHODS: We analyzed data from the first 5 years,
      2003 to 2007, of the population-based American Time Use Survey. Of 64,310
      respondents 25 years of age and older, 4267 reported 7022 episodes of health
      related self-care on their survey day. We used descriptive statistics, weighted
      to represent US adults, to describe self-reported time and logit regressions to
      analyze the odds of engaging in self-care as a function of age, sex, race, and
      other characteristics. Because health status was collected only in 2006 to 2007,
      analyses were conducted separately for 2003 to 2007 and 2006 to 2007. RESULTS: Of
      Americans 25 years of age and older, 6.6% engaged in health-related self-care
      each day. Among those reporting self-care, mean time reported was 90 minutes
      (median, 15 minutes); 20.6% reported 2 hours or more. Regressions for 2006 to
      2007 show that people aged 75 or older were 3.9 times as likely (95% CI, 2.7-5.8)
      to report self-care as persons aged 25 to 44. Compared with persons in excellent
      health, those in fair health were 2.0 times as likely (95% CI, 1.4-2.8) and those
      in poor health were 3.7 times as likely (95% CI, 2.5-5.6) to report engaging in
      self-care. Nonworking disabled persons reported self-care 4 times (95% CI, 3.1
      5.3) as often as employed persons. Sex, race/ethnicity, presence of children, and
      body mass index were also significant. CONCLUSIONS: Time spent on health-related
      self-care is disproportionately distributed across the population, with a larger
      amount of time reported by those in poor health (3.6 hours/week) and the
      nonworking disabled (3.2 hours/week). To provide patient-centered care and to
      promote optimal decisions about health-related time management when making
      recommendations for additional self-care tasks, clinicians need to talk to
      patients about how much time they are already spending on self-care.

PMID- 21737763
TI  - Glycemic control patterns and kidney disease progression among primary care
      patients with diabetes mellitus.
AB  - BACKGROUND: Reducing glycosylated hemoglobin (HbA1c) to near or less than 7% in
      patients with diabetes is associated with diminished microvascular complications,
      but this level is not consistently achieved. The purpose of this study was to
      examine the relationship between fluctuations in HbA1c and changes in estimated
      glomerular filtration rate (eGFR) and estimated stage of chronic kidney disease
      (CKD) in an academic primary care practice. METHODS: We analyzed data from 791
      diabetic primary care patients (25% white; 75% African American) enrolled between
      1998 to 2002 and followed through 2008 (mean follow-up, 7.6 +/- 1.9 years). We
      calculated baseline and final follow-up eGFR using the Modification of Diet in
      Renal Disease equation. We examined the relationship between fluctuations in
      HbA1c and changes in eGFR and stage of CKD using multivariable linear and
      logistic regression models that controlled for demographic and clinical variables
      associated with CKD progression. RESULTS: From baseline to follow-up, mean eGFR
      in African Americans declined to a greater extent and more rapidly than in
      whites. Age, mean systolic blood pressure, initial HbA1c, initial eGFR, and
      number of HbA1c values (all P<.01) were significant predictors of change in eGFR.
      Among HbA1c fluctuation measures, the strongest predictor of change in eGFR was
      the proportion of HbA1c values >7% (P=.02); however, this contributed little to
      explaining model variance. CONCLUSION: These data suggest that traditional
      demographic and clinical risk factors remain significantly associated with
      changes in eGFR and that the pattern of variability in HbA1c is only modestly
      important in contributing to changes in eGFR among African-American and white
      diabetic patients in primary care.

PMID- 21737764
TI  - Are population-based diabetes models useful for individual risk estimation?
AB  - BACKGROUND: Predictive models are increasingly used in guidelines and informed
      decision-making interventions. We compared predictions from 2 prominent models
      for diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) outcomes
      model and the Archimedes-based Diabetes Personal Health Decisions (PHD) model.
      METHODS: Ours was a simulation study comparing 10-year and 20-year model
      predictions for risks of myocardial infarction (MI), stroke, amputation,
      blindness, and renal failure for representative test cases. RESULTS: The Diabetes
      PHD model predicted substantially higher risks of MI and stroke in most cases,
      particularly for stroke and for 20-year outcomes. In contrast, the UKPDS model
      predicted risks of amputation and blindness ranging from 2-fold to infinitely
      higher than the Diabetes PHD model. Predictions for renal failure all differed by
      more than 2-fold but in a complicated pattern varying by time frame and specific
      risk factors. Relative to their predictions for white men, the UKPDS model
      predicted much lower MI and stroke risks for women and Afro-Caribbean men than
      the Diabetes PHD model did for women and black men. A substantial majority of the
      Diabetes PHD point estimates fell outside of the UKPDS outcomes model's 95% CIs.
      CONCLUSIONS: These models produced markedly different predictions. Patients and
      providers considering risk estimates from such models need to understand their
      substantial uncertainty and risk of misclassification.

PMID- 21737765
TI  - Relationships between alanine aminotransferase levels, abnormal liver
      echogenicity, and metabolic syndrome.
AB  - BACKGROUND: Elevated alanine aminotransferase (e-ALT) and abnormal liver
      echogenicity (ab-echo), as determined by sonography, have been linked to
      metabolic syndrome (MetS). However, which of these is more closely related to
      MetS, especially among older men, remains unknown. METHODS: Data from 3065 men
      aged 65 years or older who were undergoing a routine health examination and who
      were not taking any medications for MetS were analyzed retrospectively. The
      patients were divided into 4 groups: group N (n= 1228; patients have normal ALT
      and liver echogenicity); group A (n=110; patients have e-ALT but normal liver
      echogenicity); group E (n=1381; patients have ab-echo but normal ALT); group AE
      (n=346; patients have both e-ALT and ab-echo). RESULTS: Among the 3065 subjects,
      714 participants were found to have MetS (23.3%). It is not surprising that MetS
      components were highest in group AE. More interestingly, compared with group A,
      group E had higher levels of MetS components (except that high-density
      lipoprotein cholesterol levels were lower). Similar findings were confirmed by
      logistic regression. Group E had a significantly higher odds ratio of having MetS
      than group A (2.73; 95% CI, 1.565-4.763). CONCLUSIONS: Our data confirm that both
      e-ALT and ab-echo are related to a higher incidence of MetS among Taiwanese older
      men. Of these 2 abnormalities, ab-echo seems to be more closely related to MetS.
      Further studies are needed to elucidate the complex relationships between these
      factors in other age and ethnic groups.

PMID- 21737766
TI  - Uric acid as a potential cue to screen for iron overload.
AB  - BACKGROUND: It is suggested that targeted screening for hemochromatosis and iron
      overload may be worthwhile. The aim of this study was to examine uric acid as a
      potential indicator of the presence of iron overload. METHODS: We analyzed adults
      aged 20 and older in the National Health and Nutrition Examination Survey 1999 to
      2002. We computed logistic regressions controlling for age, sex, race/ethnicity,
      liver or kidney condition, and alcohol use to see the relationship between
      combinations of uric acid and ferritin with the outcomes of elevated liver
      enzymes and proteinuria. RESULTS: In unadjusted analyses, 20.7% of individuals
      with high uric acid had high ferritin levels versus 8.8% of individuals with low
      uric acid levels (P<.001). Individuals with both elevated uric acid and elevated
      ferritin levels had significantly higher liver enzymes than individuals with
      either elevated uric acid or ferritin. With low uric acid and low ferritin as the
      reference category, individuals with high uric acid and high ferritin were
      significantly more likely to also have proteinuria (odds ratio, 2.66; 95% CI,
      1.82-3.91). CONCLUSIONS: Elevated levels of uric acid is associated with elevated
      ferritin levels and may serve as a risk stratification variable for presence of
      iron overload and hemochromatosis.

PMID- 21737767
TI  - Bupropion and restless legs syndrome: a randomized controlled trial.
AB  - INTRODUCTION: Restless legs syndrome (RLS) is a common neurological disorder
      affecting 10% of the population. Most antidepressants exacerbate symptoms;
      however, correlational studies have noted symptom improvement with bupropion. The
      purpose of the current study was to examine whether, in a controlled study,
      bupropion would improve the symptoms of RLS, or at least not exacerbate them.
      METHODS: This was a double-blinded, randomized controlled trial. Twenty-nine
      participants with moderate to severe RLS received 150 mg sustained-release
      bupropion once daily, and 31 control participants received a placebo.
      Participants were followed for 6 weeks and completed standardized tools,
      including the International Restless Legs Syndrome Study Group (IRLSSG) severity
      scale. RESULTS: The primary outcome was change from baseline in IRLSSG severity
      score; lower scores were associated with improved symptoms. At 3 weeks, IRLSSG
      scores were 10.8 points lower in the bupropion group and 6.0 points lower in the
      placebo group (P=.016). At 6 weeks, IRLSSG scores were 10.4 points lower in the
      bupropion group and 7.6 points lower in the placebo group (P=.108). Bupropion was
      more effective than placebo in the treatment of RLS at 3 weeks; however, this
      difference was not statistically significant at 6 weeks. CONCLUSIONS: The data
      from our study suggest that bupropion does not exacerbate the symptoms of RLS and
      may be a reasonable choice if an antidepressant is needed in individuals with
      RLS. Larger studies that include titration of bupropion should be considered to
      determine if bupropion is appropriate for primary treatment of RLS, particularly
      considering the lower cost and favorable side effect profile compared with
      currently recommended first-line dopamine agonists.

PMID- 21737768
TI  - Incidence of Staphylococcus aureus nasal colonization and soft tissue infection
      among high school football players.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft
      tissue infections have been documented with increasing frequency in both team and
      individual sports in recent years. It also seems that the level of MRSA skin and
      soft tissue infections in the general population has increased. METHODS: One
      hundred ninety athletes from 6 local high school football teams were recruited
      for this prospective observational study to document nasal colonization and the
      potential role this plays in skin and soft tissue infections in football players
      and, in particular, MRSA infections. Athletes had nasal swabs done before their
      season started, and they filled out questionnaires regarding potential risk
      factors for skin and soft tissue infections. Those enrolled in the study were
      then observed over the course of the season for skin and soft tissue infections.
      Those infected had data about their infections collected. RESULTS: One hundred
      ninety of 386 available student athletes enrolled in the study. Forty-four of the
      subjects had nasal colonization with methicillin-susceptible S. aureus, and none
      were colonized with MRSA. There were 10 skin and soft tissue infections (8
      bacterial and 2 fungal) documented over the course of the season. All were
      treated as outpatients with oral or topical antibiotics, and none were considered
      serious. Survey data from the preseason questionnaire showed 21% with skin
      infection, 11% with methicillin-susceptible S. aureus, and none with MRSA
      infection during the past year. Three reported a remote history of MRSA
      infection. CONCLUSIONS: We documented an overall skin infection rate of 5.3%
      among high school football players over a single season. Our results suggest that
      skin and soft tissue infection may not be widespread among high school athletes
      in northeast Ohio.

PMID- 21737769
TI  - Chronic constipation: an evidence-based review.
AB  - BACKGROUND: Chronic constipation is a common condition seen in family practice
      among the elderly and women. There is no consensus regarding its exact
      definition, and it may be interpreted differently by physicians and patients.
      Physicians prescribe various treatments, and patients often adopt different over
      the-counter remedies. Chronic constipation is either caused by slow colonic
      transit or pelvic floor dysfunction, and treatment differs accordingly. METHODS:
      To update our knowledge of chronic constipation and its etiology and best
      evidence treatment, information was synthesized from articles published in
      PubMed, EMBASE, and Cochrane Database of Systematic Reviews. Levels of evidence
      and recommendations were made according to the Strength of Recommendation
      taxonomy. RESULTS: The standard advice of increasing dietary fibers, fluids, and
      exercise for relieving chronic constipation will only benefit patients with true
      deficiency. Biofeedback works best for constipation caused by pelvic floor
      dysfunction. Pharmacological agents increase bulk or water content in the bowel
      lumen or aim to stimulate bowel movements. Novel classes of compounds have
      emerged for treating chronic constipation, with promising clinical trial data.
      Finally, the link between senna abuse and colon cancer remains unsupported.
      CONCLUSIONS: Chronic constipation should be managed according to its etiology and
      guided by the best evidence-based treatment.

PMID- 21737770
TI  - Cannabis and its derivatives: review of medical use.
AB  - BACKGROUND: Use of cannabis is often an under-reported activity in our society.
      Despite legal restriction, cannabis is often used to relieve chronic and
      neuropathic pain, and it carries psychotropic and physical adverse effects with a
      propensity for addiction. This article aims to update the current knowledge and
      evidence of using cannabis and its derivatives with a view to the sociolegal
      context and perspectives for future research. METHODS: Cannabis use can be traced
      back to ancient cultures and still continues in our present society despite legal
      curtailment. The active ingredient, Delta9-tetrahydrocannabinol, accounts for
      both the physical and psychotropic effects of cannabis. Though clinical trials
      demonstrate benefits in alleviating chronic and neuropathic pain, there is also
      significant potential physical and psychotropic side-effects of cannabis. Recent
      laboratory data highlight synergistic interactions between cannabinoid and opioid
      receptors, with potential reduction of drug-seeking behavior and opiate sparing
      effects. Legal rulings also have changed in certain American states, which may
      lead to wider use of cannabis among eligible persons. CONCLUSIONS: Family
      physicians need to be cognizant of such changing landscapes with a practical
      knowledge on the pros and cons of medical marijuana, the legal implications of
      its use, and possible developments in the future.

PMID- 21737771
TI  - Having and being a personal physician: vision of the Pisacano scholars.
AB  - Having a strong relationship with a personal physician can improve patient health
      outcomes. Yet achieving and sustaining this type of patient-physician
      relationship is often not possible in the current American health care system.
      Pisacano scholars and alumni, a group of young physician leaders supported by the
      American Board of Family Medicine, gathered for a 2-day symposium in June 2010 to
      explore the meaning of personal doctoring and its importance to our work as
      family physicians. Using the techniques of appreciative inquiry, the group
      discussed three questions: What is it like to have a personal physician? What is
      it like to be a personal physician? and, What are some feasible next steps toward
      making this possible? Symposium participants concluded that achieving the ideal
      patient-physician relationship for all patients and physicians would involve
      extensive alterations to the current health care system beyond what is outlined
      in the 2010 Patient Protection and Affordable Care Act. However, in the context
      of current health reform efforts, individual physicians, researchers, and policy
      makers must not lose sight of the importance of the patient-physician
      relationship and should continue to take concrete steps on an individual and
      system level to move us closer to this ideal.

PMID- 21737772
TI  - Simvastatin-induced meralgia paresthetica.
AB  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) cause mainly
      muscular adverse effects. During the last 20 years there has been solid evidence
      of peripheral neuropathy caused by statins, with a risk of one in 10,000 patients
      treated for 1 year. Meralgia paresthetica is an entrapment neuropathy
      occasionally encountered by primary care physicians. To date there has been no
      report of entrapment neuropathy that could have been caused or aggravated by
      statins. This case report presents meralgia paresthetica aggravated by
      simvastatin use that disappeared after simvastatin cessation.

PMID- 21737773
TI  - Urine clarity inaccurate to rule out urinary tract infection in women.
AB  - BACKGROUND: A previous study suggested that, among children, a clear urine sample
      accurately rules out urinary tract infection. The aim of this study was to
      replicate this previous study done in an adult female population. METHODS: We
      analyzed 100 anonymous urine samples from female patients ages 18 to 50 years who
      were receiving care in a university hospital system. Urine samples were tested
      for clarity by determining if newsprint could be legibly read through them.
      RESULTS: Sensitivity, specificity, and positive and negative predictive values
      for the newsprint test were 13.3%, 96.5%, 40.0%, and 86.3%, respectively.
      CONCLUSION: Visual inspection of urine clarity was not sufficiently accurate to
      rule out urinary tract infection in women.

PMID- 21737774
TI  - Re: Care of patients who are worried about mercury poisoning from dental
      fillings.

PMID- 21737775
TI  - Re: Sleep and the family doctor: time to lead.

PMID- 21737776
TI  - Tumor necrosis factor receptor 1-dependent depletion of mucus in immature small
      intestine: a potential role in neonatal necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in
      premature infants. NEC is believed to occur when intestinal bacteria invade the
      intestinal epithelial layer, causing subsequent inflammation and tissue necrosis.
      Mucins are produced and secreted by epithelial goblet cells as a key component of
      the innate immune system and barrier function of the intestinal tract that help
      protect against bacterial invasion. To better understand the role of mucins in
      NEC, we quantified the number of mucus-containing small intestinal goblet cells
      present in infants with NEC and found they had significantly fewer goblet cells
      and Paneth cells compared with controls. To test whether inflammation has a
      developmentally dependent effect on intestinal goblet cells, TNF-alpha was
      injected into mice at various stages of intestinal development. TNF-alpha caused
      a loss of mucus-containing goblet cells only in immature mice and induced Muc2
      and Muc3 mRNA upregulation only in mature ileum. Only minimal changes were seen
      in apoptosis and in expression of markers of goblet cell differentiation. TNF
      alpha increased small intestinal mucus secretion and goblet cell hypersensitivity
      to prostaglandin E2 (PGE(2)), a known mucus secretagogue produced by macrophages.
      These TNF-alpha-induced changes in mucus mRNA levels required TNF receptor 2
      (TNFR2), whereas TNF-alpha-induced loss of mucus-positive goblet cells required
      TNFR1. Our findings of developmentally dependent TNF-alpha-induced alterations on
      intestinal mucus may help explain why NEC is predominantly found in premature
      infants, and TNF-alpha-induced alterations of the intestinal innate immune system
      and barrier functions may play a role in the pathogenesis of NEC itself.

PMID- 21737777
TI  - Glutamine activates peroxisome proliferator-activated receptor-gamma in
      intestinal epithelial cells via 15-S-HETE and 13-OXO-ODE: a novel mechanism.
AB  - Glutamine possesses gut-protective effects both clinically and in the laboratory.
      We have shown in a rodent model of mesenteric ischemia-reperfusion that enteral
      glutamine increased peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      and was associated with a reduction in mucosal injury and inflammation. The
      mechanism by which glutamine activates PPAR-gamma is unknown, and we hypothesized
      that it was via a ligand-dependent mechanism. Intestinal epithelial cells, IEC-6,
      were co-transfected with PPAR-gamma response element-luciferase promoter/reporter
      construct. Cells were pretreated with increasing concentrations of glutamine +/-
      GW9662 (a specific antagonist of PPAR-gamma) and analyzed for PPAR-gamma response
      element luciferase activity as an indicator of PPAR-gamma activation. PPAR-gamma
      nuclear activity was assessed by electrophoretic mobility shift assay. Cell
      lysates were subjected to tandem mass spectroscopy for measurement of
      prostaglandin and lipoxygenase metabolites. A time- and concentration-dependent
      increase in PPAR-gamma transcriptional activity, but not mRNA or protein, was
      demonstrated. Activity was abrogated by the PPAR-gamma inhibitor, GW9662, and
      changes in activity correlated with PPAR-gamma nuclear binding. Glutamine, via
      degradation to glutamate, activated the metabolic by-products of the lipoxygenase
      and linoleic acid pathways, 15-S-hydroxyeicosatetraenoic acid and dehydrogenated
      13-hydroxyoctaolecadienoic acid, known endogenous PPAR-gamma ligands in the small
      bowel. This novel mechanism may explain the gut-protective effects of enteral
      glutamine.

PMID- 21737778
TI  - Molecular analysis of the luminal- and mucosal-associated intestinal microbiota
      in diarrhea-predominant irritable bowel syndrome.
AB  - Alterations in the intestinal microbiota have been suggested as an etiological
      factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a
      molecular fingerprinting technique to compare the composition and biodiversity of
      the microbiota within fecal and mucosal niches between patients with diarrhea
      predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T
      RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene
      was used to perform microbial community composition analyses on fecal and mucosal
      samples from patients with D-IBS (n = 16) and healthy controls (n = 21).
      Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples
      revealed differences in the contribution of T-RFs to the microbiota between D-IBS
      patients and healthy controls. Further analysis revealed a significantly lower
      (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than
      healthy controls (P = 0.008). No difference in biodiversity in mucosal samples
      was detected between D-IBS patients and healthy controls. Multivariate analysis
      of T-RFLP profiles demonstrated distinct microbial communities between luminal
      and mucosal niches in all samples. Our findings of compositional differences in
      the luminal- and mucosal-associated microbiota between D-IBS patients and healthy
      controls and diminished microbial biodiversity in D-IBS fecal samples further
      support the hypothesis that alterations in the intestinal microbiota may have an
      etiological role in the pathogenesis of D-IBS and suggest that luminal and
      mucosal niches need to be investigated.

PMID- 21737779
TI  - Mybl2, downregulated during colon epithelial cell maturation, is suppressed by
      miR-365.
AB  - Altered profiles of gene expression reflect the reprogramming of intestinal
      epithelial cells during their maturation along the crypt-luminal axis. To focus
      on genes important in this process, and how they in turn are regulated, we
      identified 14 transcripts commonly downregulated in expression during lineage
      specific maturation of the immortalized cell lines Caco-2 (absorptive), HT29Cl16E
      (goblet), and HT29Cl19A (secretory) induced by contact inhibition of growth or
      the short-chain fatty acid butyrate. One such gene, Mybl2 (Myb-related protein
      B), has been linked to the stem cell phenotype, and we report is also markedly
      suppressed in maturing cells along the crypt-luminal axis in vivo. Mybl2 is not
      significantly downregulated transcriptionally during colon cell maturation, but
      we identified a potential micro-RNA (miRNA)-binding sequence in the Mybl2 3'
      untranslated region that mediates reporter gene suppression in differentiating
      colon cells. Accordingly, miRNAs predicted to bind this functional target are
      upregulated in differentiating colon epithelial cells in vitro and in vivo;
      expression of one of these, hsa-miR-365 (but not hsa-324-5p), suppresses Mybl2
      protein expression in proliferating Caco-2 cells. These data demonstrate that
      miRNA silencing plays an important role in regulating gene expression in maturing
      colon epithelial cells, and that utilizing a target-centered approach, rather
      than profiling global miRNA expression, can identify physiologically relevant,
      functional miRNAs.

PMID- 21737780
TI  - Constitutive activation of the MEK/ERK pathway inhibits intestinal epithelial
      cell differentiation.
AB  - The Ras/Raf/MEK/ERK cascade regulates intestinal epithelial cell proliferation.
      Indeed, while barely detectable in differentiated cells of the villi, ERK1/2
      activated forms are detected in the nucleus of undifferentiated human intestinal
      crypt cells. In addition, we and others have reported that ERKs are selectively
      inactivated during enterocyte differentiation. However, whether inactivation of
      the ERK pathway is necessary for inhibition of both proliferation and induction
      of differentiation of intestinal epithelial cells is unknown. Human Caco-2/15
      cells, undifferentiated crypt IEC-6 cells, and differentiating Cdx3-expressing
      IEC-6 cells were infected with retroviruses encoding either a hemagglutinin (HA)
      tagged MEK1 wild type (wtMEK) or a constitutively active S218D/S222D MEK1 mutant
      (caMEK). Protein and gene expression was assessed by Western blotting,
      semiquantitative RT-PCR, and real-time PCR. Morphology was analyzed by
      transmission electron microscopy. We found that 1) IEC-6/Cdx3 cells formed
      multicellular layers after confluence and differentiated after 30 days in
      culture, as assessed by increased polarization, microvilli formation, expression
      of differentiation markers, and ERK1/2 inhibition; 2) while activated MEK
      prevented neither the inhibition of ERK1/2 activities nor the differentiation
      process in postconfluent Caco-2/15 cells, caMEK expression prevented ERK
      inhibition in postconfluent IEC-6/Cdx3 cells, thus leading to maintenance of
      elevated ERK1/2 activities; 3) caMEK-expressing IEC-6/Cdx3 cells exhibited
      altered multicellular structure organization, poorly defined tight junctions,
      reduced number of microvilli on the apical surface, and decreased expression of
      the hepatocyte nuclear factor 1alpha transcription factor and differentiation
      markers, namely apolipoprotein A-4, fatty acid-binding protein, calbindin-3,
      mucin 2, alkaline phosphatase, and sucrase-isomaltase; and 4) increased Cdx3
      phosphorylation on serine-60 (S60) in IEC-6/Cdx3 cells expressing caMEK led to
      decreased Cdx2 transactivation potential. These results indicate that
      inactivation of the ERK pathway is required to ensure the full Cdx2/3
      transcriptional activity necessary for intestinal epithelial cell terminal
      differentiation.

PMID- 21737781
TI  - Interleukin-33 induces expression of adhesion molecules and inflammatory
      activation in human endothelial cells and in human atherosclerotic plaques.
AB  - OBJECTIVE: Interleukin (IL)-33 is the most recently described member of the IL-1
      family of cytokines and it is a ligand of the ST2 receptor. While the effects of
      IL-33 on the immune system have been extensively studied, the properties of this
      cytokine in the cardiovascular system are much less investigated. Methods/Results
      We show here that IL-33 promoted the adhesion of human leukocytes to monolayers
      of human endothelial cells and robustly increased vascular cell adhesion molecule
      1, intercellular adhesion molecule-1, endothelial selectin, and monocyte
      chemoattractant protein-1 protein production and mRNA expression in human
      coronary artery and human umbilical vein endothelial cells in vitro as well as in
      human explanted atherosclerotic plaques ex vivo. ST2-fusion protein, but not IL-1
      receptor antagonist, abolished these effects. IL-33 induced translocation of
      nuclear factor-kappaB p50 and p65 subunits to the nucleus in human coronary
      artery endothelial cells and human umbilical vein endothelial cells and
      overexpression of dominant negative form of IkappaB kinase 2 or IkappaBalpha in
      human umbilical vein endothelial cells abolished IL-33-induced adhesion molecules
      and monocyte chemoattractant protein-1 mRNA expression. We detected IL-33 and ST2
      on both protein and mRNA level in human carotid atherosclerotic plaques.
      CONCLUSIONS: We hypothesize that IL-33 may contribute to early events in
      endothelial activation characteristic for the development of atherosclerotic
      lesions in the vessel wall, by promoting adhesion molecules and proinflammatory
      cytokine expression in the endothelium.

PMID- 21737782
TI  - Rho-associated kinase activity, endothelial function, and cardiovascular risk
      factors.
AB  - OBJECTIVE: Cardiovascular diseases are associated with chronic activation of Rho
      associated kinases (ROCKs) and endothelial dysfunction. Both increased ROCK
      activity and endothelial dysfunction are thought to be closely associated with
      conventional cardiovascular risk factors. The purpose of this study was to
      determine the relationships between ROCK activity, endothelial function, and
      cardiovascular risk factors. METHODS AND RESULTS: We evaluated ROCK activity in
      peripheral leukocytes by Western blot analysis and flow-mediated vasodilation by
      ultrasonography in 242 men who had no cardiovascular or cerebrovascular diseases
      (mean age, 40+/-10 years; range, 20 to 73 years). ROCK activity was defined as
      the ratio of phospho myosin-binding subunit on myosin light chain phosphatase to
      total myosin-binding subunit. Univariate regression analysis revealed that
      leukocyte ROCK activity significantly correlated with body mass index (r=0.29,
      P=0.003); systolic blood pressure (r=0.25, P=0.01); low-density lipoprotein
      cholesterol level (r=0.21, P=0.04); and Framingham risk factor score, a
      cumulative cardiovascular risk index for heart attack (r=0.31, P<0.001), and that
      flow-mediated vasodilation significantly correlated with age (r=-0.23, P=0.02),
      body mass index (r=0.19, P=0.05), systolic blood pressure (r=-0.22, P=0.03),
      total cholesterol level (r=-0.21, P=0.04), low-density lipoprotein cholesterol
      level (r=-0.22, P=0.04), glucose level (r=-0.20, P=0.04), and Framingham risk
      factor score (r=-0.37, P<0.001). There was a significant correlation between
      leukocyte ROCK activity and flow-mediated vasodilation (r=-0.41, P<0.001).
      Multivariate analysis revealed that flow-mediated vasodilation was an independent
      predictor of leukocyte ROCK activity. CONCLUSIONS: These findings suggest that
      cumulative cardiovascular risk may enhance ROCK activity and endothelial
      dysfunction, leading to progression of cardiovascular diseases and outcomes.

PMID- 21737783
TI  - Pericyte-derived MFG-E8 regulates pathologic angiogenesis.
AB  - OBJECTIVE: MFG-E8 (also called lactadherin and SED1) is a secreted glycoprotein
      that has been previously implicated in enhancement of vascular endothelial growth
      factor-dependent angiogenesis. Major sources of MFG-E8 in vivo and precise
      mechanisms of MFG-E8 action remain undetermined. The objective of this study was
      to identify important sources of MFG-E8 in vivo and further elucidate the role(s)
      of MFG-E8 in the regulation of angiogenesis. METHODS AND RESULTS: We used
      knockout mice and anti-MFG-E8 antibodies to study MFG-E8 function in vivo. In
      melanomas and in retinas of mice with oxygen-induced retinopathy, MFG-E8
      colocalized with pericytes rather than endothelial cells, and platelet-derived
      growth factor receptor beta+ pericytes/pericyte precursors purified from tumors
      contained large amounts of MFG-E8 mRNA. Tumor- and retinopathy-associated
      angiogenesis was diminished in MFG-E8 knockout mice, and pericyte coverage of
      neovessels was reduced. Inhibition of MFG-E8 production by 10T1/2 cells
      (surrogate pericyte/pericyte precursors) using small interfering RNAs and short
      hairpin RNAs, or inhibition of MFG-E8 action with some anti-MFG-E8 antibodies,
      selectively attenuated migration in vitro. Significantly, the anti-MFG-E8
      antibodies that inhibited 10T1/2 cell migration in vitro also inhibited
      pathological angiogenesis in vivo. CONCLUSIONS: These studies strongly implicate
      MFG-E8 in pericyte/pericyte precursor function and indicate that MFG-E8-directed
      therapeutics may merit further development.

PMID- 21737785
TI  - Lytic resistance of fibrin containing red blood cells.
AB  - OBJECTIVE: Arterial thrombi contain variable amounts of red blood cells (RBCs),
      which interact with fibrinogen through an eptifibatide-sensitive receptor and
      modify the structure of fibrin. In this study, we evaluated the modulator role of
      RBCs in the lytic susceptibility of fibrin. METHODS AND RESULTS: If fibrin is
      formed at increasing RBC counts, scanning electron microscopy evidenced a
      decrease in fiber diameter from 150 to 96 nm at 40% (v/v) RBCs, an effect
      susceptible to eptifibatide inhibition (restoring 140 nm diameter). RBCs
      prolonged the lysis time in a homogeneous-phase fibrinolytic assay with tissue
      plasminogen activator (tPA) by up to 22.7+/-1.6%, but not in the presence of
      eptifibatide. Confocal laser microscopy using green fluorescent protein-labeled
      tPA and orange fluorescent fibrin showed that 20% to 40% (v/v) RBCs significantly
      slowed down the dissolution of the clots. The fluorescent tPA variant did not
      accumulate on the surface of fibrin containing RBCs at any cell count above 10%.
      The presence of RBCs in the clot suppressed the tPA-induced plasminogen
      activation, resulting in 45% less plasmin generated after 30 minutes of
      activation at 40% (v/v) RBCs. CONCLUSIONS: RBCs confer lytic resistance to fibrin
      resulting from modified fibrin structure and impaired plasminogen activation
      through a mechanism that involves eptifibatide-sensitive fibrinogen-RBC
      interactions.

PMID- 21737784
TI  - Bone morphogenetic protein endothelial cell precursor-derived regulator regulates
      retinal angiogenesis in vivo in a mouse model of oxygen-induced retinopathy.
AB  - OBJECTIVE: Bone morphogenetic proteins (BMPs) are potently proangiogenic;
      however, the mechanisms underlying the regulation of vessel development by BMPs
      are not fully understood. To assess the significance of BMP endothelial cell
      precursor-derived regulator (BMPER) in blood vessel formation in vivo, we
      investigated its role in retinal angiogenesis. METHODS AND RESULTS: In a model of
      oxygen-induced retinopathy, Bmper mRNA expression and protein levels are
      downregulated, correlating with the initiation of Sma and Mad related protein
      phosphorylation in endothelial cells. Moreover, Bmper haploinsufficiency results
      in an increased rate of retinal revascularization, with retinas from Bmper+/-
      mice displaying increased numbers of branching points and angiogenic sprouts at
      the leading edge of the newly formed vasculature. Furthermore, although Bmper
      haploinsufficiency does not alter Bmp expression, it does lead to an increase in
      BMP signaling, as evidenced by increased phosphorylated Sma and Mad related
      protein levels in endothelial cells and increased expression of known BMP target
      genes. CONCLUSIONS: These observations provide compelling evidence that BMPER is
      important in the regulation of BMP signaling and revascularization in the hypoxic
      retina. These bring forth the possibility of novel therapeutic approaches for
      pathological angiogenesis based on manipulation of BMP signaling.

PMID- 21737786
TI  - Induction of smooth muscle cell migration during arteriogenesis is mediated by
      Rap2.
AB  - OBJECTIVE: Collateral artery growth or arteriogenesis is the primary means of the
      circulatory system to maintain blood flow in the face of major arterial
      occlusions. Arteriogenesis depends on activation of fibroblast growth factor
      (FGF) receptors, but relatively little is known about downstream mediators of FGF
      signaling. METHODS AND RESULTS: We screened for signaling components that are
      activated in response to administration of FGF-2 to cultured vascular smooth
      muscle cells (VSMCs) and detected a significant increase of Rap2 but not of other
      Ras family members, which corresponded to a strong upregulation of Rap2 and C-Raf
      in growing collaterals from rabbits with femoral artery occlusion. Small
      interfering RNAs directed against Rap2 did not affect FGF-2 induced proliferation
      of VSMC but strongly inhibited their migration. Inhibition of FGF receptor-1
      (FGFR1) signaling by infusion of a sulfonic acid polymer or infection with a
      dominant-negative FGFR1 adenovirus inhibited Rap2 upregulation and collateral
      vessel growth. Similarly, expression of dominant-negative Rap2 blocked
      arteriogenesis, whereas constitutive active Rap2 enhanced collateral vessel
      growth. CONCLUSIONS: Rap2 is part of the arteriogenic program and acts downstream
      of the FGFR1 to stimulate VSMC migration. Specific modulation of Rap2 might be an
      attractive target to manipulate VSMC migration, which plays a role in numerous
      pathological processes.

PMID- 21737787
TI  - Intramyocardial, autologous CD34+ cell therapy for refractory angina.
AB  - RATIONALE: A growing number of patients with coronary disease have refractory
      angina. Preclinical and early-phase clinical data suggest that intramyocardial
      injection of autologous CD34+ cells can improve myocardial perfusion and
      function. OBJECTIVE: Evaluate the safety and bioactivity of intramyocardial
      injections of autologous CD34+ cells in patients with refractory angina who have
      exhausted all other treatment options. METHODS AND RESULTS: In this prospective,
      double-blind, randomized, phase II study (ClinicalTrials.gov identifier:
      NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1*10(5)
      or 5*10(5) cells/kg) of mobilized autologous CD34+ cells or an equal volume of
      diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable
      myocardium with a NOGA mapping injection catheter. The primary outcome measure
      was weekly angina frequency 6 months after treatment. Weekly angina frequency was
      significantly lower in the low-dose group than in placebo-treated patients at
      both 6 months (6.8+/-1.1 versus 10.9+/-1.2, P=0.020) and 12 months (6.3+/-1.2
      versus 11.0+/-1.2, P=0.035); measurements in the high-dose group were also lower,
      but not significantly. Similarly, improvement in exercise tolerance was
      significantly greater in low-dose patients than in placebo-treated patients (6
      months: 139+/-151 versus 69+/-122 seconds, P=0.014; 12 months: 140+/-171 versus
      58+/-146 seconds, P=0.017) and greater, but not significantly, in the high-dose
      group. During cell mobilization and collection, 4.6% of patients had cardiac
      enzyme elevations consistent with non-ST segment elevation myocardial infarction.
      Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths
      among cell-treated patients. CONCLUSIONS: Patients with refractory angina who
      received intramyocardial injections of autologous CD34+ cells (10(5) cells/kg)
      experienced significant improvements in angina frequency and exercise tolerance.
      The cell-mobilization and -collection procedures were associated with cardiac
      enzyme elevations, which will be addressed in future studies.

PMID- 21737788
TI  - Network for activation of human endothelial cells by oxidized phospholipids: a
      critical role of heme oxygenase 1.
AB  - RATIONALE: Oxidized palmitoyl arachidonyl phosphatidylcholine (Ox-PAPC)
      accumulates in atherosclerotic lesions, is proatherogenic, and influences the
      expression of more than 1000 genes in endothelial cells. OBJECTIVE: To elucidate
      the major pathways involved in Ox-PAPC action, we conducted a systems analysis of
      endothelial cell gene expression after exposure to Ox-PAPC. METHODS AND RESULTS:
      We used the variable responses of primary endothelial cells from 149 individuals
      exposed to Ox-PAPC to construct a network that consisted of 11 groups of genes,
      or modules. Modules were enriched for a broad range of Gene Ontology pathways,
      some of which have not been identified previously as major Ox-PAPC targets.
      Further validating our method of network construction, modules were consistent
      with relationships established by cell biology studies of Ox-PAPC effects on
      endothelial cells. This network provides novel hypotheses about molecular
      interactions, as well as candidate molecular regulators of inflammation and
      atherosclerosis. We validated several hypotheses based on network connections and
      genomic association. Our network analysis predicted that the hub gene CHAC1
      (cation transport regulator homolog 1) was regulated by the ATF4 (activating
      transcription factor 4) arm of the unfolded protein response pathway, and here we
      showed that ATF4 directly activates an element in the CHAC1 promoter. We showed
      that variation in basal levels of heme oxygenase 1 (HMOX1) contribute to the
      response to Ox-PAPC, consistent with its position as a hub in our network. We
      also identified G-protein-coupled receptor 39 (GPR39) as a regulator of HMOX1
      levels and showed that it modulates the promoter activity of HMOX1. We further
      showed that OKL38/OSGN1 (oxidative stress-induced growth inhibitor), the hub gene
      in the blue module, is a key regulator of both inflammatory and antiinflammatory
      molecules. CONCLUSIONS: Our systems genetics approach has provided a broad view
      of the pathways involved in the response of endothelial cells to Ox-PAPC and also
      identified novel regulatory mechanisms.

PMID- 21737789
TI  - Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from
      human embryonic stem cell-derived mesoderm.
AB  - RATIONALE: Human embryonic stem cells can form cardiomyocytes when cultured under
      differentiation conditions. Although the initiating step of mesoderm formation is
      well characterized, the subsequent steps that promote for cardiac lineages are
      poorly understood and limit the yield of cardiomyocytes. OBJECTIVE: Our aim was
      to develop a human embryonic stem cell-based high-content screening assay to
      discover small molecules that drive cardiogenic differentiation after mesoderm is
      established to improve our understanding of the biology involved. Screening of
      libraries of small-molecule pathway modulators was predicted to provide insight
      into the cellular proteins and signaling pathways that control stem cell
      cardiogenesis. METHODS AND RESULTS: Approximately 550 known pathway modulators
      were screened in a high-content screening assay, with hits being called out by
      the appearance of a red fluorescent protein driven by the promoter of the cardiac
      specific MYH6 gene. One potent small molecule was identified that inhibits
      transduction of the canonical Wnt response within the cell, which demonstrated
      that Wnt inhibition alone was sufficient to generate cardiomyocytes from human
      embryonic stem cell-derived mesoderm cells. Transcriptional profiling of
      inhibitor-treated compared with vehicle-treated samples further indicated that
      inhibition of Wnt does not induce other mesoderm lineages. Notably, several other
      Wnt inhibitors were very efficient in inducing cardiogenesis, including a
      molecule that prevents Wnts from being secreted by the cell, which confirmed that
      Wnt inhibition was the relevant biological activity. CONCLUSIONS: Pharmacological
      inhibition of Wnt signaling is sufficient to drive human mesoderm cells to form
      cardiomyocytes; this could yield novel tools for the benefit of pharmaceutical
      and clinical applications.

PMID- 21737790
TI  - Differential roles of GSK-3beta during myocardial ischemia and
      ischemia/reperfusion.
AB  - RATIONALE: Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart
      during ischemia/reperfusion (I/R), yet the underlying mechanisms of
      cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be
      elucidated. OBJECTIVE: We studied the molecular mechanism mediating the effect of
      GSK-3beta activation/inhibition upon myocardial injury during prolonged ischemia
      and I/R. METHODS AND RESULTS: Beta isoform-specific inhibition of GSK-3 by
      dominant negative GSK-3beta in transgenic mice (Tg-DnGSK-3beta) or in
      heterozygous GSK-3beta knock-out mice (GSK-3beta+/-) significantly increased,
      whereas activation of GSK-3beta in constitutively active GSK-3beta knock-in mice
      (betaKI) significantly decreased, myocardial ischemic injury after prolonged
      ischemia. In contrast, inhibition of GSK-3beta in Tg-DnGSK-3beta or GSK-3beta+/-
      significantly reduced, while activation of GSK-3beta in betaKI significantly
      enhanced, myocardial I/R injury. Inhibition of GSK-3beta stimulated mTOR
      signaling and inhibited autophagy through a rapamycin-sensitive (mTOR dependent)
      mechanism. Rapamycin enhanced autophagy and, at the same time, abolished the
      effects of GSK-3beta inhibition on both prolonged ischemic injury and I/R injury.
      Importantly, the influence of rapamycin over the effects of GSK-3beta inhibition
      on myocardial injury was reversed by inhibition of autophagy. CONCLUSIONS: Our
      results suggest that beta isoform-specific inhibition of GSK-3 exacerbates
      ischemic injury but protects against I/R injury by modulating mTOR and autophagy.

PMID- 21737791
TI  - Orai1-mediated I (CRAC) is essential for neointima formation after vascular
      injury.
AB  - RATIONALE: The molecular correlate of the calcium release-activated calcium
      current (I(CRAC)), the channel protein Orai1, is upregulated in proliferative
      vascular smooth muscle cells (VSMC). However, the role of Orai1 in vascular
      disease remains largely unknown. OBJECTIVE: The goal of this study was to
      determine the role of Orai1 in neointima formation after balloon injury of rat
      carotid arteries and its potential upregulation in a mouse model of VSMC
      remodeling. METHODS AND RESULTS: Lentiviral particles encoding short-hairpin RNA
      (shRNA) targeting either Orai1 (shOrai1) or STIM1 (shSTIM1) caused knockdown of
      their respective target mRNA and proteins and abrogated store-operated calcium
      entry and I(CRAC) in VSMC; control shRNA was targeted to luciferase
      (shLuciferase). Balloon injury of rat carotid arteries upregulated protein
      expression of Orai1, STIM1, and calcium-calmodulin kinase IIdelta2
      (CamKIIdelta2); increased proliferation assessed by Ki67 and PCNA and decreased
      protein expression of myosin heavy chain in medial and neointimal VSMC.
      Incubation of the injured vessel with shOrai1 prevented Orai1, STIM1, and
      CamKIIdelta2 upregulation in the media and neointima; inhibited cell
      proliferation and markedly reduced neointima formation 14 days post injury;
      similar results were obtained with shSTIM1. VSMC Orai1 and STIM1 knockdown
      inhibited nuclear factor for activated T-cell (NFAT) nuclear translocation and
      activity. Furthermore, Orai1 and STIM1 were upregulated in mice carotid arteries
      subjected to ligation. CONCLUSIONS: Orai1 is upregulated in VSMC during vascular
      injury and is required for NFAT activity, VSMC proliferation, and neointima
      formation following balloon injury of rat carotids. Orai1 provides a novel target
      for control of VSMC remodeling during vascular injury or disease.

PMID- 21737792
TI  - Neuronal calcium sensor-1 promotes immature heart function and hypertrophy by
      enhancing Ca2+ signals.
AB  - RATIONALE: Neuronal calcium sensor-1 (NCS-1) regulates various neuronal
      functions. Although it is expressed in the heart, very little is known about its
      cardiac functions. OBJECTIVE: This study aimed to identify the physiological and
      pathological roles of NCS-1 in the heart. METHODS AND RESULTS: We characterized
      the cardiac functions of knockout mice (Ncs1(-/-)) and identified NCS-1 as a
      novel regulator of cardiac Ca(2+) signaling, specifically in immature and
      hypertrophic hearts. NCS-1 was highly expressed in young hearts, and its deletion
      decreased survival and contractile function in young mice. Intracellular Ca(2+)
      levels and sarcoplasmic reticulum Ca(2+) content were significantly lower in
      Ncs1(-/-) myocytes than in wild-type cells. This was due to reduced
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity in Ncs1(-/-)
      myocytes, which led to reduced sarcoplasmic reticulum Ca(2+) uptake and release.
      NCS-1 physically and functionally interacted with inositol 1,4,5-trisphosphate
      receptors (IP(3)Rs) in the heart. In addition, IP(3)R stimulation resulted in
      phosphorylation of CaMKII-delta, which was enhanced by NCS-1 overexpression.
      These results suggest that a functional link exists between NCS-1, IP(3)R
      function, and CaMKII activation that may affect global Ca(2+) signals in the
      immature heart. Furthermore, NCS-1 was upregulated in hypertrophic hearts, and
      hormone-induced hypertrophy was largely prevented in Ncs1(-/-) hearts. Inhibitors
      of IP(3)Rs, CaMKII, and calcineurin all prevented NCS-1-induced hypertrophy,
      which suggests the involvement of these pathways. CONCLUSIONS: NCS-1 is an
      important regulator of immature heart function and hypertrophy, and it functions
      in part by promoting IP(3)R function, followed by CaMKII-dependent signal
      activation.

PMID- 21737793
TI  - Flow diversion for intracranial aneurysms: a review.
AB  - The introduction of flow diverters for treatment of intracranial aneurysms
      represents a major paradigm shift in the treatment of these lesions. The
      theoretical hallmark of flow diverters is the treatment of the diseased segment
      harboring the aneurysm instead of treating the aneurysm itself. Flow diverters
      are designed to induce disruption of flow near the aneurysm neck while preserving
      flow into parent vessel and adjacent branches. After flow diversion, intra
      aneurysmal thrombosis occurs, followed by shrinkage of the aneurysmal sac as the
      thrombus organizes and retracts. Preliminary clinical series document effective
      treatment of wide-neck and/or large and giant aneurysms with acceptable
      complication rates. However, several questions remain unanswered related to the
      incidence and mechanisms of aneurysm rupture after treatment with flow diverters,
      fate of small perforating vessels, and long-term patency rates.

PMID- 21737794
TI  - Association between VEGF polymorphisms and homocysteine levels in patients with
      ischemic stroke and silent brain infarction.
AB  - BACKGROUND AND PURPOSE: Vascular endothelial growth factor (VEGF) plays a role in
      atherosclerosis-related diseases such as cerebrovascular or cardiovascular
      diseases. However, the effect of VEGF -2578C>A, -1154G>A, -634G>C, and 936C>T
      polymorphisms on the susceptibility to stroke and silent brain infarction has not
      been reported. METHODS: Using polymerase chain reaction-amplified DNA, VEGF
      polymorphisms were analyzed in 615 patients with ischemic stroke, 376 patients
      with silent brain infarction, and 494 control subjects. RESULTS: The AA and CC+CA
      (C allele bearing) genotype frequencies of the -2578C>A polymorphism and the
      CT+TT (T allele-bearing) genotype frequency of the 936C>T polymorphism were
      significantly different between the stroke and control groups (false discovery
      rate-adjusted probability values of 0.016, 0.044, and 0.044, respectively). When
      stratified by the size of the occluded vessel, the VEGF polymorphisms were
      associated with patients with multiple small-artery occlusions. Several
      haplotypes of the VEGF polymorphisms were significantly different between the
      control and stroke groups. With respect to silent brain infarction, the
      difference in the frequency of the -634G>C polymorphism between the GC+CC (C
      allele-bearing) genotype and the controls was marginally significant (false
      discovery rate-adjusted probability value of 0.056). On the other hand, the 
      634G>C and 936C>T polymorphisms were associated with plasma homocysteine levels
      of patients with multiple or single small-artery occlusions, respectively.
      CONCLUSIONS: This study suggests that VEGF polymorphisms and haplotypes are
      possible genetic determinants for the risk of ischemic stroke, particularly in
      patients with multiple small-artery occlusions. However, VEGF polymorphisms had
      only a weak association with plasma homocysteine levels in the Korean population.

PMID- 21737795
TI  - Factors associated with impaired kidney function and its impact on long-term
      outcome in young ischemic stroke.
AB  - BACKGROUND AND PURPOSE: After ischemic stroke, kidney dysfunction is linked to
      poor outcomes in the elderly, but regarding young patients, data are lacking.
      METHODS: We investigated estimated glomerular filtration rate (eGFR) on admission
      according to the Modification of Diet in Renal Disease equation in 958
      consecutive patients aged 15 to 49 years with their first-ever ischemic stroke.
      Logistic regression adjusted for demographics and stroke risk factors served to
      identify factors related to low (<60) and high (>120 mL/min/1.73 m(2)) eGFR. In
      the long-term follow-up (mean, 8.9+/-3.8 years) study, Cox proportional hazards
      analysis described the association between eGFR and the following end points:
      nonfatal/fatal ischemic stroke; composite vascular event of any stroke,
      myocardial infarction, revascularization/other arterial occlusive event, or
      vascular death; and death of any cause. RESULTS: Estimated GFR was normal in 809
      (84.4%), low in 43 (4.5%), and high in 106 (11.1%) patients. Type 1 diabetes (OR,
      18.84; 95% CI, 8.65 to 41.03), hypertension (4.29; 1.94 to 9.48), and
      cardiovascular disease (2.66; 1.19 to 5.96) were independently associated with
      low eGFR. Type 2 diabetes (3.82; 1.93 to 7.55), lower age (0.95 per year; 0.93 to
      0.98), and male gender (1.74; 1.08 to 2.82) were associated with high eGFR. Both
      low (hazard ratio, 5.73; 95% CI, 3.54 to 9.25) and high eGFR (1.78; 1.01 to 3.14)
      were associated with long-term mortality when adjusted for age, gender, risk
      factors, stroke severity, and subtype. No independent association appeared
      between eGFR and vascular events. CONCLUSIONS: Despite their different associated
      risk factors in our young patient cohort, both low and high eGFR predicted long
      term mortality after ischemic stroke.

PMID- 21737796
TI  - Statins promote the growth of experimentally induced cerebral aneurysms in
      estrogen-deficient rats.
AB  - BACKGROUND AND PURPOSE: The pathogenesis of cerebral aneurysms is linked to
      inflammation, degradation of the extracellular matrix, and vascular wall
      apoptosis. Statins exert pleiotropic effects on the vasculature, independent of
      their cholesterol-lowering properties. To explore the detailed pathogenesis of
      cerebral aneurysms, we examined their progression in a rat model and studied
      whether statins prevent their initiation and growth. METHODS: Cerebral aneurysms
      were induced in female rats subjected to hypertension, increased hemodynamic
      stress, and estrogen deficiency. The development of aneurysm was assessed
      morphologically on corrosion casts. The effects of pravastatin (5, 25, or 50
      mg/kg per day) and of simvastatin (5 mg/kg per day) on their aneurysms were
      studied. Human brain endothelial cells were also used to determine the effects of
      pravastatin. RESULTS: Pravastatin (5 mg/kg per day) reduced endothelial damage
      and inhibited aneurysm formation; there was an association with increased
      endothelial nitric oxide synthase (eNOS) levels and a decrease in human brain
      endothelial cell adhesion molecules. Unexpectedly, 25 mg/kg per day and 50 mg/kg
      per day pravastatin and 5 mg/kg per day simvastatin promoted aneurysmal growth,
      and high-dose pravastatin induced aneurysmal rupture. The deleterious effects
      exerted by these statins were associated with an increase in apoptotic caspase-3
      levels and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
      positive cells, suggesting that statins exert bidirectional effects. CONCLUSIONS:
      Our results provide the first evidence that cerebral aneurysm growth is partly
      associated with apoptosis and issue a warning that statins exert bidirectional
      effects on cerebral aneurysms. Additional intensive research is necessary to
      understand better their mechanisms and to identify patients in whom the
      administration of statins may elicit deleterious effects.

PMID- 21737797
TI  - Synergistic memory impairment through the interaction of chronic cerebral
      hypoperfusion and amlyloid toxicity in a rat model.
AB  - BACKGROUND AND PURPOSE: Vascular pathology and Alzheimer disease (AD) pathology
      have been shown to coexist in the brains of dementia patients. We investigated
      how cognitive impairment could be exacerbated in a rat model of combined injury
      through the interaction of chronic cerebral hypoperfusion and amyloid beta
      (Abeta) toxicity. METHODS: In Wistar rats, chronic cerebral hypoperfusion was
      modeled by permanent occlusion of bilateral common carotid arteries (BCCAo).
      Further, AD pathology was modeled by bilateral intracerebroventricular Abeta
      (Abeta toxicity) using a nonphysiological Abeta peptide (Abeta 25 to 35). The
      experimental animals were divided into 4 groups, including sham, single injury
      (Abeta toxicity or BCCAo), and combined injury (BCCAo-Abeta toxicity) groups (n=7
      per group) . Cerebral blood flow and metabolism were measured using small animal
      positron emission tomography. A Morris water maze task, novel object location and
      recognition tests, and histological investigation, including neuronal cell death,
      apoptosis, neuroinflammation, and AD-related pathology, were performed. RESULTS:
      Spatial memory impairment was synergistically exacerbated in the BCCAo-Abeta
      toxicity group as compared to the BCCAo or Abeta toxicity groups (P<0.05).
      Compared to the sham group, neuroinflammation with microglial or astroglial
      activation was increased both in multiple white matter lesions and the
      hippocampus in other experimental groups. AD-related pathology was enhanced in
      the BCCAo-Abeta toxicity group compared to the Abeta toxicity group. CONCLUSIONS:
      Our experimental results support a clinical hypothesis of the deleterious
      interaction between chronic cerebral hypoperfusion and Abeta toxicity. Chronic
      cerebral hypoperfusion-induced perturbation in the equilibrium of AD-related
      pathology may exacerbate cognitive impairment in a rat model of combined injury.

PMID- 21737798
TI  - Collateral flow averts hemorrhagic transformation after endovascular therapy for
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Collaterals sustain the ischemic penumbra to limit growth
      of the infarct core before revascularization, yet the impact of baseline
      collateral flow on hemorrhagic transformation (HT) after endovascular therapy
      remains unknown. METHODS: A collaborative study from 2 stroke centers in distinct
      geographic regions included 222 consecutive patients who received endovascular
      therapy for acute cerebral ischemia. The influence of collaterals on HT was
      analyzed in distinct case scenarios relative to baseline collateral grade at
      angiography (0 to 1 versus 2 to 4) and recanalization (Thrombolysis in Myocardial
      Ischemia scale, 0 to 1 versus 2 to 3): good collaterals and successful
      recanalization (n=98), poor collaterals with successful recanalization (n=43),
      good collaterals and no recanalization(n=46), and poor collaterals and no
      recanalization (n=35). RESULTS: HT after endovascular therapy occurred in 103
      (46.4%) patients; 42 (18.9%) were symptomatic. HT was more frequently observed in
      patients with poor collaterals and recanalization than in other groups (P=0.048).
      When revascularization was achieved, patients with poorer collaterals were more
      likely to have symptomatic worsening with HT (r=-0.181, P=0.032). Multiple
      logistic regression analysis identified aggressive treatment (OR, 2.558 for Merci
      clot retrieval; 95% CI, 1.153 to 5.678; OR, 3.618 for combined fibrinolytics and
      mechanical therapy; 95% CI, 1.551 to 8.437; and OR, 2.085 for intravenous
      thrombolysis before endovascular therapy; 95% CI, 1.096 to 3.969), poor
      collaterals and recanalization (OR, 2.666; 95% CI, 1.163 to 6.113), and serum
      glucose levels (OR, 1.007; 95% CI, 1.000 to 1.014) as independent predictors of
      HT. CONCLUSIONS: Angiographic grade of collateral flow strongly influences the
      rate of HT after therapeutic recanalization for acute ischemic stroke. Collateral
      status readily available from baseline angiography may therefore refine
      therapeutic decision-making in acute cerebral ischemia.

PMID- 21737799
TI  - Notch activation enhances the microglia-mediated inflammatory response associated
      with focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Activation of Notch worsens ischemic brain damage as
      antisense knockdown or pharmacological inhibition of the Notch pathway reduces
      the infarct size and improves the functional outcome in a mouse model of stroke.
      We sought to determine whether Notch activation contributes to postischemic
      inflammation by directly modulating the microglial innate response. METHODS: The
      microglial response and the attendant inflammatory reaction were evaluated in
      Notch1 antisense transgenic (Tg) and in nontransgenic (non-Tg) mice subjected to
      middle cerebral artery occlusion with or without treatment with a gamma-secretase
      inhibitor (GSI). To investigate the impact of Notch on microglial effector
      functions, primary mouse microglia and murine BV-2 microglial cell line were
      exposed to oxygen glucose deprivation or lipopolysaccharide in the presence or
      absence of GSI. Immunofluorescence labeling, Western blotting, and reverse
      transcription polymerase chain reaction were performed to measure microglial
      activation and production of inflammatory cytokines. The nuclear translocation of
      nuclear factor-kappaB in microglia was assessed by immunohistochemistry. The
      neurotoxic potential of microglia was determined in cocultures. RESULTS: Notch1
      antisense mice exhibit significantly lower numbers of activated microglia and
      reduced proinflammatory cytokine expression in the ipsilateral ischemic cortices
      compared to non-Tg mice. Microglial activation also was attenuated in Notch1
      antisense cultures and in non-Tg cultures treated with GSI. GSI significantly
      reduced nuclear factor-kappaB activation and expression of proinflammatory
      mediators and markedly attenuated the neurotoxic activity of microglia in
      cocultures. CONCLUSIONS: These findings establish a role for Notch signaling in
      modulating the microglia innate response and suggest that inhibition of Notch
      might represent a complementary therapeutic approach to prevent reactive gliosis
      in stroke and neuroinflammation-related degenerative disorders.

PMID- 21737800
TI  - Corpus callosum and experimental stroke: studies in callosotomized rats and
      acallosal mice.
AB  - BACKGROUND AND PURPOSE: Interhemispheric inhibition via the corpus callosum has
      been proposed as an exacerbating factor in outcome from stroke. METHODS: We
      measured infarct volume and behavioral outcome after middle cerebral artery
      occlusion in callosotomized rats and acallosal mice. RESULTS: Neither callosotomy
      in rats nor callosal agenesis in mice improved infarct volume or behavioral
      outcome after middle cerebral artery occlusion. CONCLUSIONS: These findings argue
      against a role for transcallosal projections in exacerbating focal cerebral
      ischemia.

PMID- 21737801
TI  - Programmed death-1 pathway limits central nervous system inflammation and
      neurologic deficits in murine experimental stroke.
AB  - BACKGROUND AND PURPOSE: Evaluation of infarct volumes and infiltrating immune
      cell populations in mice after middle cerebral artery occlusion strongly
      implicates a mixture of both pathogenic and regulatory immune cell subsets that
      affect stroke outcome. Our goal was to evaluate the contribution of the well
      described coinhibitory pathway, programmed death (PD)-1, to the development of
      middle cerebral artery occlusion. METHODS: Infarct volumes, functional outcomes,
      and effects on infiltrating immune cell populations were compared in wild-type
      C57BL/6 versus PD-1-deficient mice after 60 minutes middle cerebral artery
      occlusion and 96 hours reperfusion. RESULTS: The results clearly demonstrate a
      previously unrecognized activity of the PD-1 pathway to limit infarct volume,
      recruitment of inflammatory cells from the periphery, activation of macrophages
      and central nervous system microglia, and functional neurological deficits. These
      regulatory functions were associated with increased percentages of circulating PD
      ligand-1 and PD-ligand-2 expressing CD19(+) B-cells in blood, the spleen, and
      central nervous system with the capacity to inhibit activation of inflammatory T
      cells and central nervous system macrophages and microglial cells through
      upregulated PD-1. CONCLUSIONS: Our novel observations are the first to implicate
      PD-1 signaling as a major protective pathway for limiting central nervous system
      inflammation in middle cerebral artery occlusion. This inhibitory circuit would
      likely be pivotal in reducing stroke-associated Toll-like receptor-2- and Toll
      like receptor-4-mediated release of neurotoxic factors by activated central
      nervous system microglia.

PMID- 21737802
TI  - Iodinated contrast media and cerebral hemorrhage after intravenous thrombolysis.
AB  - BACKGROUND AND PURPOSE: Iodinated contrast is increasingly used in CT perfusion
      or angiographic examinations in acute stroke. Increased risk of intracranial
      hemorrhage (ICH) complicating microcatheter contrast injections has recently been
      reported in the second Interventional Management of Stroke (IMS 2) trial with
      contrast toxicity potentially contributory. METHODS: We reviewed clinical and
      radiological data on all patients treated with intravenous alteplase at a single
      center between May 2003 and November 2008. RESULTS: Of 312 patients treated with
      intravenous alteplase, 69 (22.1%) received intravenous iodinated contrast in
      volumes between 50 and 150 mL. Incidence of symptomatic ICH defined as per
      European Cooperative Acute Stroke Study 2 was 16 of 312 (5.1%; 95% CI, 2.7% to
      7.6%); among patients not given contrast, it was 12 of 243 (4.9%; 2.2% to 7.7%)
      compared with 4 of 69 (5.8%; 0.3% to 11.3%) in those given contrast. Incidence of
      symptomatic ICH defined as per Safe Implementation of Thrombolysis in Stroke
      MOnitoring Study (SITS-MOST) criteria was 12 of 312 (3.9%; 1.7% to 6%), 9 of 243
      (3.7%; 1.3% to 6%) among those not given contrast, and 3 of 69 (4.4%; 95% CI, 
      0.5% to 9.2%) among those given contrast. Patients with symptomatic ICH were
      older, had higher pretreatment National Institutes of Health Stroke Scale, and
      blood glucose than those without symptomatic ICH. In logistic regression
      analysis, pretreatment blood glucose was the only significant predictor of
      symptomatic ICH by either definition (OR, 1.23; 95% CI, 1.03 to 1.48 per mmol/L
      increment; P=0.024). Contrast administration or dose was not associated with
      symptomatic ICH. CONCLUSIONS: Intravenous iodinated contrast in doses typically
      required for CT angiography and perfusion imaging was not associated with
      symptomatic intracranial hemorrhage in patients treated with alteplase.

PMID- 21737803
TI  - Natural course of perihemorrhagic edema after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: There is only limited knowledge on the time course of
      perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH). We aimed to
      investigate the chronological PHE course and its relation to in-hospital
      mortality in a large retrospective ICH cohort. METHODS: Patients with
      supratentorial ICH treated at our institution between 2006 and 2009, who had
      received at least 3 CT scans in the course of conservative treatment, were
      included in the present analysis. PHE at Days 1, 2, 3, 4 to 6, 7 to 11, 12 to 16,
      17 to 21, and >22 was assessed using a threshold based semiautomatic volumetric
      algorithm. A chart review was performed to achieve data on duration of stay,
      ventilation, treatment with external ventricular drains, and in-hospital
      mortality. RESULTS: Two hundred nineteen patients aged 69.9+/-10.5 years with
      deep (n=103) or lobar (n=116) ICH were included in the study. Mean ICH volume was
      35.7+/-31.5 mL. Mean absolute PHE volume significantly increased from initially
      32.6+/-29.9 mL to 63.7+/-46.7 mL at Days 7 to 11. No significant changes were
      observed at later time points. ICH volume was strongly correlated with absolute
      PHE volume (rho=0.8, P<0.001) and inversely correlated with relative PHE (rho=
      0.4 to -0.5, P<0.001). Increase in absolute PHE between Days 1 and 3 was
      significantly predictive for in-hospital mortality (P=0.014, ExpB=1.04).
      CONCLUSIONS: PHE develops early after ICH and doubles within the first 7 to 11
      days after the initial bleeding event. This additional mass effect may contribute
      to secondary clinical deterioration and mortality, especially in larger ICH.
      Because of its inverse correlation with ICH volume, relative PHE may not be
      suitable for analyses considering the clinical impact of PHE.

PMID- 21737804
TI  - Restoring neuronal function after stroke by cell replacement: anatomic and
      functional considerations.
AB  - BACKGROUND AND PURPOSE: A major challenge to effective treatment after stroke is
      the restoration of neuronal function. In recent years, cell-based therapies for
      stroke have been explored in experimental animal models, and the results have
      suggested behavioral improvements. However, the anatomic targets of a cell-based
      stroke therapy and the relationship of cell grafts to post stroke reorganization
      are poorly understood, which results in difficulties defining strategies for
      neuronal substitution. Given that stroke causes a variety of secondary changes at
      locations beyond the infarct lesion, overcoming these difficulties is even more
      important. SUMMARY OF REVIEW: We describe which brain structures and cell types
      are candidates for substitution and how new neuronal functionality could be
      implemented in a damaged brain by capitalizing on current concepts of post stroke
      plasticity.

PMID- 21737805
TI  - Apixaban in atrial fibrillation: from bleeding cows to 21st century medicinal
      chemistry.

PMID- 21737806
TI  - Atherogenic dyslipidemia in patients with transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: There is mounting evidence that atherogenic dyslipidemia
      (ie, low high-density lipoprotein cholesterol combined with high triglyceride
      concentrations) is an independent predictor of high cardiovascular risk and
      possibly of stroke. METHODS: All patients included in the SOS-TIA cohort
      underwent an initial standardized evaluation, including medical history, physical
      examination, routine blood biochemistry, and diagnostic testing, and were
      followed for 1 year. Lipid profile was evaluated under fasting conditions.
      Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol
      blood concentration <= 40 mg/dL and triglycerides >= 150 mg/dL. RESULTS: Among
      1471 consecutive patients with transient ischemic attack (TIA) or minor stroke,
      overall prevalence of atherogenic dyslipidemia was 5.8%, but varied from 4.6% to
      11.1%, depending on final diagnosis (possible TIA or TIA with a cerebral ischemic
      lesion, respectively). Prevalence of atherogenic dyslipidemia was independently
      associated with male sex, diabetes, and body mass index, but not with ABCD2
      score. Atherogenic dyslipidemia also strongly associated with symptomatic
      intracranial stenosis >= 50% (adjusted odds ratio, 2.77; 95% CI, 1.38-5.55), but
      not with symptomatic extracranial stenosis >= 50% (adjusted odds ratio, 1.20; 95%
      CI, 0.64-2.26). Despite appropriate secondary prevention treatment, 90-day stroke
      risk was greater in patients with versus without atherogenic dyslipidemia (4.8%
      versus 1.7%; P=0.04). CONCLUSIONS: The atherogenic dyslipidemia phenotype in
      patients with TIA may be associated with intracranial artery stenosis and higher
      risk of early recurrent stroke. Additional data are needed to confirm these
      findings and to assess the best way to reduce important residual risk in such
      patients.

PMID- 21737807
TI  - Intravenous thrombolysis of basilar artery occlusion: predictors of
      recanalization and outcome.
AB  - BACKGROUND AND PURPOSE: Basilar artery occlusion has a high mortality rate (85%
      to 95%) if untreated. We describe a large single-center cohort treated mostly
      with intravenous alteplase and heparin. METHODS: The cohort included 116 patients
      with angiography-verified basilar artery occlusion. We studied baseline
      characteristics, frequencies of recanalization and symptomatic intracranial
      hemorrhage, and 3-month outcome (modified Rankin Scale [mRS]). RESULTS: Thirty
      patients (25.9%) had mRS 0 to 2, 42 patients (36.2%) had moderate outcome (mRS, 0
      3), 26 patients (22.4%) required daily help (mRS, 4-5), and 48 patients (41.4%)
      died. Eighteen patients (15.7%) developed symptomatic intracranial hemorrhage. In
      patients with post-treatment angiogram available (n=91), 59 patients (64.8%) had
      a complete or partial recanalization. Radiological location of basilar artery
      occlusion was known in 55 of 91 instances, and recanalization was associated
      directly with clot location at the top-of-basilar (odds ratio, 4.8 [1.1-22];
      P=0.048). Independent outcome (mRS 0-2) was associated with lower age and
      National Institutes of Health Stroke Scale (NIHSS) score at baseline. Age, nil or
      minimal recanalization, and symptomatic intracranial hemorrhage were
      independently associated with fatal outcome. Sixteen of 71 patients (22.5%) who
      presented with coma eventually reached moderate outcome, and additional 8
      patients (11.3%) progressed to mRS 4. CONCLUSIONS: Whereas recanalization after
      intravenous thrombolysis strongly predicts survival and moderate outcome,
      therapeutic techniques should concentrate on clot location. Although most adverse
      baseline variables, age, symptom severity, but also coma are beyond control, it
      should not preclude thrombolysis, which may permit independent survival.

PMID- 21737808
TI  - Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Plasma matrix metalloproteinase-9 levels predict
      posttissue plasminogen activator (tPA) hemorrhage. METHODS: The authors
      investigated the effect of minocycline on plasma matrix metalloproteinase-9 in
      acute ischemic stroke in the Minocycline to Improve Neurological Outcome in
      Stroke (MINOS) trial and a comparison group. RESULTS: Matrix metalloproteinase-9
      level decreased at 72 hours compared with baseline in MINOS (tPA, P=0.0022; non
      tPA, P=0.0066) and was lower than in the non-MINOS comparison group at 24 hours
      (tPA, P<0.0001; non-tPA, P=0.0019). CONCLUSIONS: Lower plasma matrix
      metalloproteinase-9 was seen among tPA-treated subjects in the MINOS trial.
      Combining minocycline with tPA may prevent the adverse consequences of
      thrombolytic therapy through suppression of matrix metalloproteinase-9 activity.

PMID- 21737809
TI  - Acute perfusion and diffusion abnormalities predict early new MRI lesions 1 week
      after minor stroke and transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Transient ischemic attack and minor stroke are associated
      with high ischemic recurrence in the first week. We prospectively studied the
      correlation between baseline diffusion/perfusion deficits and development of new
      ischemic lesions. METHODS: Patients with transient ischemic attack and those with
      minor stroke (n=50) underwent MRI at admission. Acute perfusion-weighted imaging
      deficit (Tmax+2-second delay) and diffusion-weighted imaging (DWI) lesion volumes
      were measured planimetrically. Follow-up scans were examined for new DWI/fluid
      attenuated inversion recovery lesions at Days 7 and 30. RESULTS: Twenty-eight
      patients (56%) had acute DWI lesions. New DWI lesions developed in 9 of 50
      patients (18%) at 1 week and 11 of 50 (cumulative 22%) at 4 weeks. Patients with
      new infarcts were more likely to have baseline DWI lesions (chi2=8.264, P=0.003).
      Baseline DWI lesion volume was significantly larger in those who developed new
      lesions at Day 7 (median, 13.2 mL; interquartile range, 12 versus median 0.1 mL;
      interquartile range, 2 mL; P<0.001) and Day 30 (11.1 mL; interquartile range, 13
      mL versus 0.1 mL; interquartile range, 13 mL; P<0.001). Thirty-eight patients had
      baseline perfusion-weighted imaging. Patients with recurrent lesions were more
      likely to have baseline perfusion deficits (chi2=19.5, P<0.0001). All new lesions
      developed within the baseline hypoperfused regions. Baseline DWI lesion volume
      predicted new lesion development at day 7 (OR, 1.17 per mL; CI, 1.05 to 1.30;
      P=0.005) and Day 30 (OR, 1.39 per mL; CI, 1.03 to 1.26; P=0.009) by regression
      analysis. CONCLUSIONS: Early recurrence of stroke is much more likely in patients
      with larger baseline DWI and perfusion-weighted imaging lesions. MRI lesion
      "recurrence" appears to be related to completion of the natural history of the
      original cerebrovascular syndrome rather than de novo events in most patients.

PMID- 21737810
TI  - Letter by Pristipino and Hamon regarding article, "cerebral microembolism during
      coronary angiography: a randomized comparison between femoral and radial arterial
      access".

PMID- 21737811
TI  - Atherosclerotic plaque vulnerability as an explanation for the increased risk of
      stroke in elderly undergoing carotid artery stenting.
AB  - BACKGROUND AND PURPOSE: Recent randomized trials showed an increased
      periprocedural risk for stroke with increasing age in patients undergoing carotid
      artery stenting. Manipulation of atherosclerotic plaques during carotid artery
      stenting can result in plaque rupture with subsequent superimposed thrombus
      formation, embolization, and cerebrovascular events. We hypothesized that
      atherosclerotic plaques become more unstable with increasing age and thereby
      might provide insight into the age-related increased risk of cerebrovascular
      events during carotid artery stenting. METHODS: Carotid atherosclerotic plaques
      were harvested from 1385 consecutive patients undergoing carotid endarterectomy
      between 2002 and 2010. Carotid plaques were quantitatively analyzed for
      macrophages, smooth muscle cells, and microvessels; and semiquantitatively
      analyzed for collagen, calcifications lipid cores, and intraplaque hemorrhages.
      Patients were divided in 4 groups by age: <60, 60 to 69, 70 to 79, and >=80
      years. Measures of association between age as a continuous variable and
      histological characteristics were also calculated. RESULTS: Increasing age was
      associated with a decrease in the amount of smooth muscle cells in the carotid
      plaque. More plaques with large atheroma and heavy plaque calcifications were
      observed among elderly patients. After correction for baseline differences, risk
      factors, and medication use, age was independently associated with a more
      vulnerable carotid plaque composition. CONCLUSIONS: Plaque stability decreases
      gradually with age. Older patients with carotid stenosis have relatively unstable
      plaques with low smooth muscle cell content, a high amount of large lipid cores,
      and more calcified plaques as compared with younger patients. The underlying
      vulnerable plaque composition in the elderly might be an important contributing
      factor to the increased risk of stroke for older patients undergoing carotid
      artery stenting.

PMID- 21737813
TI  - Atrogin1/MAFbx: what atrophy, hypertrophy, and cardiac failure have in common.

PMID- 21737814
TI  - Lipid metabolism by gut microbes and atherosclerosis.

PMID- 21737815
TI  - Introduction to the series on novel aspects of cardiovascular G-protein-coupled
      receptor signaling.

PMID- 21737816
TI  - Biased ligands for better cardiovascular drugs: dissecting G-protein-coupled
      receptor pharmacology.
AB  - Drug discovery efforts targeting G-protein-coupled receptors (GPCR) have been
      immensely successful in creating new cardiovascular medicines. Currently marketed
      GPCR drugs are broadly classified as either agonists that activate receptors or
      antagonists that prevent receptor activation by endogenous stimuli. However, GPCR
      couple to a multitude of intracellular signaling pathways beyond classical G
      protein signals, and these signals can be independently activated by biased
      ligands to vastly expand the potential for new drugs at these classic targets. By
      selectively engaging only a subset of a receptor's potential intracellular
      partners, biased ligands may deliver more precise therapeutic benefit with fewer
      side effects than current GPCR-targeted drugs. In this review, we discuss the
      history of biased ligand research, the current understanding of how biased
      ligands exert their unique pharmacology, and how research into GPCR signaling has
      uncovered previously unappreciated capabilities of receptor pharmacology. We
      focus on several receptors to illustrate the approaches taken and discoveries
      made, and how these are steadily illuminating the intricacies of GPCR
      pharmacology. Discoveries of biased ligands targeting the angiotensin II type 1
      receptor and of separable pharmacology suggesting the potential value of biased
      ligands targeting the beta-adrenergic receptors and nicotinic acid receptor
      GPR109a highlight the powerful clinical promise of this new category of potential
      therapeutics.

PMID- 21737817
TI  - G protein-dependent and G protein-independent signaling pathways and their impact
      on cardiac function.
AB  - G protein-coupled receptors signal through a variety of mechanisms that impact
      cardiac function, including contractility and hypertrophy. G protein-dependent
      and G protein-independent pathways each have the capacity to initiate numerous
      intracellular signaling cascades to mediate these effects. G protein-dependent
      signaling has been studied for decades and great strides continue to be made in
      defining the intricate pathways and effectors regulated by G proteins and their
      impact on cardiac function. G protein-independent signaling is a relatively newer
      concept that is being explored more frequently in the cardiovascular system.
      Recent studies have begun to reveal how cardiac function may be regulated via G
      protein-independent signaling, especially with respect to the ever-expanding
      cohort of beta-arrestin-mediated processes. This review primarily focuses on the
      impact of both G protein-dependent and beta-arrestin-dependent signaling pathways
      on cardiac function, highlighting the most recent data that illustrate the
      comprehensive nature of these mechanisms of G protein-coupled receptor signaling.

PMID- 21737819
TI  - Blood vessel remodeling and physical inactivity in humans.
AB  - Physical inactivity is associated with an increase in cardiovascular risk that
      cannot be fully explained by traditional or novel risk factors. Inactivity is
      also associated with changes in hemodynamic stimuli, which exert direct effects
      on the vasculature leading to remodeling and a proatherogenic phenotype. In this
      review, we synthesize and summarize in vivo evidence relating to the impact of
      local and systemic models of physical inactivity on conduit arteries, resistance
      vessels, and the microcirculation in humans. Taken together, the literature
      suggests that a rapid inward structural remodeling of vessels occurs in response
      to physical inactivity. The magnitude of this response is dependent on the "dose"
      of inactivity. Moreover, changes in vascular function are found at resistance and
      microvessel levels in humans. In conduit arteries, a strong interaction between
      vascular function and structure is present, which results in conflicting data
      regarding the impact of inactivity on conduit artery function. While much of the
      cardioprotective effect of exercise is related to the nitric oxide pathway,
      deconditioning may primarily be associated with activation of vasoconstrictor
      pathways. The effects of deconditioning on the vasculature are therefore not
      simply the opposite of those in response to exercise training. Given the
      importance of sedentary behavior, future studies should provide further insight
      into the impact of inactivity on the vasculature and other (novel) markers of
      vascular health. Moreover, studies should examine the role of (hemodynamic)
      stimuli that underlie the characteristic vascular adaptations during
      deconditioning. Our review concludes with some suggestions for future research
      directions.

PMID- 21737818
TI  - Compartmentalization of beta-adrenergic signals in cardiomyocytes.
AB  - Activation of adrenergic receptors (AR) represents the primary mechanism to
      increase cardiac performance under stress. Activated betaAR couple to Gs protein,
      leading to adenylyl cyclase-dependent increases in secondary-messenger cyclic
      adenosine monophosphate (cAMP) to activate protein kinase A. The increased
      protein kinase A activities promote phosphorylation of diversified substrates,
      ranging from the receptor and its associated partners to proteins involved in
      increases in contractility and heart rate. Recent progress with live-cell imaging
      has drastically advanced our understanding of the betaAR-induced cAMP and protein
      kinase A activities that are precisely regulated in a spatiotemporal fashion in
      highly differentiated myocytes. Several features stand out: membrane location of
      betaAR and its associated complexes dictates the cellular compartmentalization of
      signaling; betaAR agonist dose-dependent equilibrium between cAMP production and
      cAMP degradation shapes persistent increases in cAMP signals for sustained
      cardiac contraction response; and arrestin acts as an agonist dose-dependent
      master switch to promote cAMP diffusion and propagation into intracellular
      compartments by sequestrating phosphodiesterase isoforms associated with the
      betaAR signaling cascades. These features and the underlying molecular mechanisms
      of dynamic regulation of betaAR complexes with adenylyl cyclase and
      phosphodiesterase enzymes and the implication in heart failure are discussed.

PMID- 21737820
TI  - Tempol attenuates the exercise pressor reflex independently of neutralizing
      reactive oxygen species in femoral artery ligated rats.
AB  - In decerebrate rats, we reported previously that the exercise pressor reflex
      arising from a limb whose femoral artery was occluded for 72 h before the
      experiment was significantly higher than the exercise pressor reflex arising from
      a contralateral freely perfused limb. These findings prompted us to examine
      whether reactive oxygen species contributed to the augmented pressor reflex in
      rats with femoral artery occlusion. We found that the pressor reflex arising from
      the limb whose femoral artery was occluded for 72 h before the experiment (31 +/-
      5 mmHg) was attenuated by tempol (10 mg), a superoxide dismutase (SOD) mimetic
      (18 +/- 5 mmHg, n = 9, P < 0.05), that was injected into the arterial supply of
      the hindlimb. In contrast, the pressor reflex arising from a freely perfused
      hindlimb (20 +/- 3 mmHg) was not attenuated by tempol (17 +/- 4 mmHg, n = 10, P =
      0.49). Nevertheless, we found no difference in the increase in 8-isoprostaglandin
      F(2alpha) levels, an index of reactive oxygen species, in response to contraction
      between freely perfused (3.76 +/- 0.82 pg/ml, n = 19) and 72-h occluded (3.51 +/-
      0.92 pg/ml, n = 22, P = 0.90) hindlimbs. Moreover, tempol did not reduce the 8
      isoprostaglandin F(2alpha) levels during contraction in either group (P > 0.30).
      A second SOD mimetic, tiron (200 mg/kg), had no effect on the exercise pressor
      reflex in either the rats with freely perfused hindlimbs or in those with
      occluded femoral arteries. These findings suggest that tempol attenuated the
      exercise pressor reflex in the femoral artery-occluded hindlimb by a mechanism
      that was independent of its ability to scavenge reactive oxygen species.

PMID- 21737821
TI  - Chronic oscillatory strain induces MLCK associated rapid recovery from acute
      stretch in airway smooth muscle cells.
AB  - A deep inspiration (DI) temporarily relaxes agonist-constricted airways in normal
      subjects, but in asthma airways are refractory and may rapidly renarrow, possibly
      due to changes in the structure and function of airway smooth muscle (ASM).
      Chronic largely uniaxial cyclic strain of ASM cells in culture causes several
      structural and functional changes in ASM similar to that in asthma, including
      increases in contractility, MLCK content, shortening velocity, and shortening
      capacity. However, changes in recovery from acute stretch similar to a DI have
      not been measured. We have therefore measured the response and recovery to large
      stretches of cells modified by chronic stretching and investigated the role of
      MLCK. Chronic, 10% uniaxial cyclic stretch, with or without a strain gradient,
      was administered for up to 11 days to cultured cells grown on Silastic membranes.
      Single cells were then removed from the membrane and subjected to 1 Hz
      oscillatory stretches up to 10% of the in situ cell length. These oscillations
      reduced stiffness by 66% in all groups (P < 0.05). Chronically strained cells
      recovered stiffness three times more rapidly than unstrained cells, while the
      strain gradient had no effect. The stiffness recovery in unstrained cells was
      completely inhibited by the MLCK inhibitor ML-7, but recovery in strained cells
      exhibiting increased MLCK was slightly inhibited. These data suggest that chronic
      strain leads to enhanced recovery from acute stretch, which may be attributable
      to the strain-induced increases in MLCK. This may also explain in part the more
      rapid renarrowing of activated airways following DI in asthma.

PMID- 21737822
TI  - Point: high altitude is for the birds!

PMID- 21737823
TI  - Reduced TrkB expression results in precocious age-like changes in neuromuscular
      structure, neurotransmission, and muscle function.
AB  - Acute blockade of signaling through the tyrosine kinase receptor B (TrkB)
      attenuates neuromuscular transmission and fragments postsynaptic acetylcholine
      receptors (AChRs) in adult mice, suggesting that TrkB signaling is a key
      regulator of neuromuscular function. Using immunohistochemical, histological, and
      in vitro muscle contractile techniques, we tested the hypothesis that
      constitutively reduced TrkB expression would disrupt neuromuscular pre- and
      postsynaptic structure, neurotransmission, muscle fiber size, and muscle function
      in the soleus muscle of 6- to 8-mo-old TrkB+/- mice compared with age-matched
      littermates. Age-like expansion of postsynaptic AChR area, AChR fragmentation,
      and denervation was observed in TrkB+/- mice similar to that found in 24-mo-old
      wild-type mice. Neurotransmission failure was increased in TrkB+/- mice,
      suggesting that these morphologic changes were sufficient to alter synaptic
      function. Reduced TrkB expression resulted in decreased muscle strength and fiber
      cross-sectional area. Immunohistochemical and muscle retrograde labeling
      experiments show that motor neuron number and size are unaffected in TrkB+/-
      mice. These results suggest that TrkB- signaling at the neuromuscular junction
      plays a role in synaptic stabilization, neurotransmission, and muscle function
      and may impact the aging process of sarcopenia.

PMID- 21737824
TI  - The action of the canine diaphragm on the lower ribs depends on activation.
AB  - Conventional wisdom maintains that the diaphragm lifts the lower ribs during
      isolated contraction. Recent studies in dogs have shown, however, that
      supramaximal, tetanic stimulation of the phrenic nerves displaces the lower ribs
      caudally and inward. In the present study, the hypothesis was tested that the
      action of the canine diaphragm on these ribs depends on the magnitude of muscle
      activation. Two experiments were performed. In the first, the C5 and C6 phrenic
      nerve roots were selectively stimulated in 6 animals with the airway occluded,
      and the level of diaphragm activation was altered by adjusting the stimulation
      frequency. In the second experiment, all the inspiratory intercostal muscles were
      severed in 7 spontaneously breathing animals, so that the diaphragm was the only
      muscle active during inspiration, and neural drive was increased by a succession
      of occluded breaths. The changes in airway opening pressure and the craniocaudal
      displacements of ribs 5 and 10 were measured in each animal. The data showed that
      1) contraction of the diaphragm causes the upper ribs to move caudally; 2) during
      phrenic nerve stimulation, the lower ribs move cranially when the level of
      diaphragm activation is low, but they move caudally when the level of muscle
      activation is high and the entire rib cage is exposed to pleural pressure; and 3)
      during spontaneous diaphragm contraction, however, the lower ribs always move
      cranially, even when neural drive is elevated and the change in pleural pressure
      is large. It is concluded that the action of the diaphragm on the lower ribs
      depends on both the magnitude and the mode of muscle activation. These findings
      can reasonably explain the apparent discrepancies between previous studies. They
      also imply that observations made during phrenic nerve stimulation do not
      necessarily reflect the physiological action of the diaphragm.

PMID- 21737825
TI  - Regional stiffening with aging in tibialis anterior tendons of mice occurs
      independent of changes in collagen fibril morphology.
AB  - The incidence of tendon degeneration and rupture increases with advancing age.
      The mechanisms underlying this increased risk remain unknown but may arise
      because of age-related changes in tendon mechanical properties and structure. Our
      purpose was to determine the effect of aging on tendon mechanical properties and
      collagen fibril morphology. Regional mechanical properties and collagen fibril
      characteristics were determined along the length of tibialis anterior (TA)
      tendons from adult (8- to 12-mo-old) and old (28- to 30-mo-old) mice. Tangent
      modulus of all regions along the tendons increased in old age, but the increase
      was substantially greater in the proximal region adjacent to the muscle than in
      the rest of the tendon. Overall end-to-end modulus increased with old age at
      maximum tendon strain (799 +/- 157 vs. 1,419 +/- 91 MPa) and at physiologically
      relevant strain (377 +/- 137 vs. 798 +/- 104 MPa). Despite the dramatic changes
      in tendon mechanical properties from adulthood to old age, collagen fibril
      morphology and packing fraction remained relatively constant in all tendon
      regions examined. Since tendon properties are influenced by their external
      loading environment, we also examined the effect of aging on TA muscle
      contractile properties. Maximum isometric force did not differ between the age
      groups. We conclude that TA tendons stiffen in a region-dependent manner
      throughout the life span, but the changes in mechanical properties are not
      accompanied by corresponding changes in collagen fibril morphology or force
      generating capacity of the TA muscle.

PMID- 21737826
TI  - Seven days of aerobic exercise training improves conduit artery blood flow
      following glucose ingestion in patients with type 2 diabetes.
AB  - The vasodilatory effects of insulin account for up to 40% of insulin-mediated
      glucose disposal; however, insulin-stimulated vasodilation is impaired in
      individuals with type 2 diabetes, limiting perfusion and delivery of glucose and
      insulin to target tissues. To determine whether exercise training improves
      conduit artery blood flow following glucose ingestion, a stimulus for increasing
      circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound)
      during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or
      obese (body mass index, 34 +/- 1 kg/m2), sedentary (peak oxygen consumption, 23
      +/- 1 ml.kg-1.min-1) individuals (53 +/- 2 yr) with non-insulin-dependent type 2
      diabetes (HbA1c, 6.63 +/- 0.18%) before and after 7 days of supervised treadmill
      and cycling exercise (60 min/day, 60-75% heart rate reserve). Fasting glucose,
      insulin, and FBF were not significantly different after 7 days of exercise, nor
      were glucose or insulin responses to the OGTT. However, estimates of whole body
      insulin sensitivity (Matsuda insulin sensitivity index) increased (P < 0.05).
      Before exercise training, FBF did not change significantly during the OGTT (1 +/-
      7, -7 +/- 5, 0 +/- 6, and 0 +/- 5% of fasting FBF at 75, 90, 105, and 120 min,
      respectively). In contrast, after exercise training, FBF increased by 33 +/- 9,
      39 +/- 14, 34 +/- 7, and 48 +/- 18% above fasting levels at 75, 90, 105, and 120
      min, respectively (P < 0.05 vs. corresponding preexercise time points).
      Additionally, postprandial glucose responses to a standardized breakfast meal
      consumed under "free-living" conditions decreased during the final 3 days of
      exercise (P < 0.05). In conclusion, 7 days of aerobic exercise training improves
      conduit artery blood flow during an OGTT in individuals with type 2 diabetes.

PMID- 21737827
TI  - Effects of the menstrual cycle on muscle recruitment and oxidative fuel selection
      during cold exposure.
AB  - Differences in core temperature and body heat content, generally observed between
      the luteal and follicular phase of the menstrual cycle, have been reported to
      modulate the thermogenic activity of cold-exposed women. However, it is unclear
      how this change in whole body shivering activity will influence fuel selection.
      The goal of this study was to quantify the effects of the menstrual cycle on
      muscle recruitment and oxidative fuel selection during low-intensity shivering.
      Electromyographic activity of eight large muscles was monitored while
      carbohydrate, lipid, and protein utilization was simultaneously quantified in the
      follicular and luteal phases of the menstrual cycle in nonacclimatized women
      shivering at a low intensity. The onset (~25 min), intensity (~15% of maximal
      voluntary contraction), and pattern (~6 shivering bursts/min) of the shivering
      response did not differ between menstrual cycle phases, regardless of differences
      in core temperature and hormone levels. This resulted in lipids remaining the
      predominant substrate, contributing 75% of total heat production, independent of
      menstrual phase. We conclude that hormone fluctuations inherent in the menstrual
      cycle do not affect mechanisms of substrate utilization in the cold. Whether the
      large contribution of lipids to total heat production in fuel selection confers a
      survival advantage remains to be established.

PMID- 21737828
TI  - Effects of different acute hypoxic regimens on tissue oxygen profiles and
      metabolic outcomes.
AB  - Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both
      obesity and OSA are associated with insulin resistance and systemic inflammation,
      which may be attributable to tissue hypoxia. We hypothesized that a pattern of
      hypoxic exposure determines both oxygen profiles in peripheral tissues and
      systemic metabolic outcomes, and that obesity has a modifying effect. Lean and
      obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60)
      [inspired O2 fraction (Fi(O2)) 21-5%, 60/h], IH 12 times/h (Fi(O2) 5% for 15 s,
      12/h), sustained hypoxia (SH; Fi(O2) 10%), or normoxia while fasting. Tissue
      oxygen partial pressure (Pti(O2)) in liver, skeletal muscle and epididymal fat,
      plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis
      factor-alpha (TNF-alpha) were measured. In lean mice, IH60 caused oxygen swings
      in the liver, whereas fluctuations of Pti(O2) were attenuated in muscle and
      abolished in fat. In obese mice, baseline liver Pti(O2) was lower than in lean
      mice, whereas muscle and fat Pti(O2) did not differ. During IH, Pti(O2) was
      similar in obese and lean mice. All hypoxic regimens caused insulin resistance.
      In lean mice, hypoxia significantly increased leptin, especially during SH (44
      fold); IH60, but not SH, induced a 2.5- to 3-fold increase in TNF-alpha secretion
      by fat. Obesity was associated with striking increases in leptin and TNF-alpha,
      which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen
      fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced
      insulin resistance, but inflammation was increased only by IH60 in lean mice.
      Obesity caused severe inflammation, which was not augmented by acute hypoxic
      regimens.

PMID- 21737829
TI  - Effect of experimental muscle pain on maximal voluntary activation of human
      biceps brachii muscle.
AB  - Muscle pain has widespread effects on motor performance, but the effect of pain
      on voluntary activation, which is the level of neural drive to contracting
      muscle, is not known. To determine whether induced muscle pain reduces voluntary
      activation during maximal voluntary contractions, voluntary activation of elbow
      flexors was assessed with both motor-point stimulation and transcranial magnetic
      stimulation over the motor cortex. In addition, we performed a psychophysical
      experiment to investigate the effect of induced muscle pain across a wide range
      of submaximal efforts (5-75% maximum). In all studies, elbow flexion torque was
      recorded before, during, and after experimental muscle pain by injection of 1 ml
      of 5% hypertonic saline into biceps. Injection of hypertonic saline evoked deep
      pain in the muscle (pain rating ~5 on a scale from 0 to 10). Experimental muscle
      pain caused a small (~5%) but significant reduction of maximal voluntary torque
      in the motor-point and motor cortical studies (P < 0.001 and P = 0.045,
      respectively; n = 7). By contrast, experimental muscle pain had no significant
      effect on voluntary activation when assessed with motor-point and motor cortical
      stimulation although voluntary activation tested with motor-point stimulation was
      reduced by ~2% in contractions after pain had resolved (P = 0.003). Furthermore,
      induced muscle pain had no significant effect on torque output during submaximal
      efforts (P > 0.05; n = 6), which suggests that muscle pain did not alter the
      relationship between the sense of effort and production of voluntary torque.
      Hence, the present study suggests that transient experimental muscle pain in
      biceps brachii has a limited effect on central motor pathways.

PMID- 21737830
TI  - Clinical and magnetic resonance imaging results of arthroscopic full-layer repair
      of bursal-side partial-thickness rotator cuff tears.
AB  - BACKGROUND: Partial rotator cuff tears are being diagnosed more often because of
      high-resolution magnetic resonance imaging (MRI). Articular-side partial tears
      are much more common than bursal-side tears, and all-inside or PASTA repairs that
      preserve the bursal tissue have gained popularity. In contrast, there have been
      few reports about preserving the articular tissue during bursal tear repair.
      PURPOSE: To report clinical and radiological results of bursal-side partial
      thickness rotator cuff tear (PTRCT) repair with preservation of as much of the
      intact articular-side tendon as possible. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: From May 2006 to March 2008, 109 patients with PTRCT
      underwent arthroscopic repair. Among them, 38 consecutive patients who received a
      full-layer repair on the bursal side for greater than 50% thickness PTRCT were
      retrospectively evaluated. All repairs were performed with a technique that
      preserved intact articular fibers. To assess the outcome, pain visual analog
      scale (PVAS), American Shoulder and Elbow Surgeon (ASES) score, and Constant
      score were evaluated at final follow-up. Postoperative MRI at least 6 months
      after surgery was evaluated for repair integrity. RESULTS: All 38 patients (21
      men and 17 women) were available for final follow-up. The mean age at surgery was
      50.8 years (range, 30-58 years), and the mean follow-up time was 26.9 months
      (range, 24-41 months). There were 21 right shoulders and 17 left shoulders, for
      which the mean time from the onset of symptoms to surgery was 47.0 months (+/
      83.3 months). The PVAS improved from 5.2 (+/-2.5) to 1.6 (+/-1.5), and mean ASES
      and Constant scores improved from 53.1 (+/-20.4) and 59.9 (+/-15.3) to 87.2 (+/
      9.4) and 83.2 (+/-12.0), respectively. Postoperative MRI was available in 33
      patients at a mean 8.2 months after surgery. Twenty-nine shoulders (87.9%) had an
      intact repaired tendon, while 3 patients had shown partial-thickness delaminated
      retears, and 1 patient demonstrated a full-thickness retear on postoperative MRI.
      CONCLUSION: For bursal-side PTRCT, clinical outcomes and tendon healing showed
      good results at a minimum 2 years after surgery, with minimal damage to intact
      articular tendon fibers on postoperative MRIs.

PMID- 21737831
TI  - Prospective correlation between serum relaxin concentration and anterior cruciate
      ligament tears among elite collegiate female athletes.
AB  - BACKGROUND: The female anterior cruciate ligament may be more susceptible to
      injury than the male anterior cruciate ligament because of the gender-specific
      expression of receptors for relaxin, a collagenolytic hormone that promotes
      remodeling of the anterior cruciate ligament. PURPOSE: This study was undertaken
      to investigate whether collegiate female athletes with elevated serum relaxin
      concentrations (SRC) sustain anterior cruciate ligament tears at an increased
      rate compared with those with lower SRC. STUDY DESIGN: Cohort study (prognosis);
      Level of evidence, 2. METHODS: From 2005 to 2010, 143 Division I female athletes
      from 2 universities participating in sports at high risk for anterior cruciate
      ligament tears (basketball, lacrosse, field hockey, soccer, gymnastics, and
      volleyball) were recruited to participate. Questionnaires and urine luteinizing
      hormone (LH) tests were used to determine participants' anterior cruciate
      ligament injury and menstrual history and to identify their mid-luteal phase or
      projected cycle days 21 to 24. Serum samples were obtained for progesterone and
      relaxin ELISA (enzyme-linked immunosorbent assay) analysis. Participants were
      monitored for anterior cruciate ligament injury over their 4-year National
      Collegiate Athletic Association athletic career. RESULTS: A total of 128
      participants completed the study and were eligible for data analysis. The
      cumulative incidence of complete anterior cruciate ligament tear over the 4-year
      study period was 21.9%, and varied significantly by sport (P < .001). The mean
      SRC for athletes with anterior cruciate ligament tears (6.0 +/- 8.1 pg/mL) was
      significantly higher than that for those without anterior cruciate ligament tears
      (1.8 +/- 3.4 pg/mL; P = .013). In subgroup analysis of the 46 athletes who had
      detectable SRC, the cumulative incidence of anterior cruciate ligament tear was
      14 of 46 (30.4%); the mean SRC among athletes with anterior cruciate ligament
      tears (14 of 46) was 12.1 +/- 7.7 pg/mL and without anterior cruciate ligament
      tears (32 of 46), 5.7 +/- 3.6 pg/mL (P = .002). When 6.0 pg/mL was set as the SRC
      cutoff for screening athletes for risk of anterior cruciate ligament tear in the
      subgroup with detectable relaxin levels, the test had 71% sensitivity, 69%
      specificity, 52% positive predictive value, 88% negative predictive value, and a
      relative risk of 4.4. These values were significant by chi(2) test (P = .003) and
      receiver operating characteristic analysis (P = .002). CONCLUSION: Elite female
      athletes with anterior cruciate ligament tears have higher SRC than those without
      tears. Those with an SRC greater than 6.0 pg/mL had over 4 times increased risk
      for a tear. CLINICAL RELEVANCE: Females with higher serum relaxin levels may be
      at increased risk for anterior cruciate ligament tears. Further investigation of
      the clinical utility of SRC testing is warranted.

PMID- 21737832
TI  - Does platelet-rich plasma accelerate recovery after rotator cuff repair? A
      prospective cohort study.
AB  - BACKGROUND: Platelet-rich plasma (PRP) has been recently used to enhance and
      accelerate the healing of musculoskeletal injuries and diseases, but evidence is
      still lacking, especially on its effects after rotator cuff repair. HYPOTHESIS:
      Platelet-rich plasma accelerates recovery after arthroscopic rotator cuff repair
      in pain relief, functional outcome, overall satisfaction, and enhanced structural
      integrity of repaired tendon. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: Forty-two patients with full-thickness rotator cuff tears were included.
      Patients were informed about the use of PRP before surgery and decided themselves
      whether to have PRP placed at the time of surgery. Nineteen patients underwent
      arthroscopic rotator cuff repair with PRP and 23 without. Platelet-rich plasma
      was prepared via plateletpheresis and applied in the form of a gel threaded to a
      suture and placed at the interface between tendon and bone. Outcomes were
      assessed preoperatively and at 3, 6, 12, and finally at a minimum of 16 months
      after surgery (at an average of 19.7 +/- 1.9 months) with respect to pain, range
      of motion, strength, and overall satisfaction, and with respect to functional
      scores as determined using the following scoring systems: the American Shoulder
      and Elbow Surgeon (ASES) system, the Constant system, the University of
      California at Los Angeles (UCLA) system, the Disabilities of the Arm, Shoulder
      and Hand (DASH) system, the Simple Shoulder Test (SST) system, and the Shoulder
      Pain and Disability Index (SPADI) system. At a minimum of 9 months after surgery,
      repaired tendon structural integrities were assessed by magnetic resonance
      imaging. RESULTS: Platelet-rich plasma gel application to arthroscopic rotator
      cuff repairs did not accelerate recovery with respect to pain, range of motion,
      strength, functional scores, or overall satisfaction as compared with
      conventional repair at any time point. Whereas magnetic resonance imaging
      demonstrated a retear rate of 26.7% in the PRP group and 41.2% in the
      conventional group, there was no statistical significance between the groups (P =
      .388). CONCLUSION: The results suggest that PRP application during arthroscopic
      rotator cuff repair did not clearly demonstrate accelerated recovery clinically
      or anatomically except for an improvement in internal rotation. Nevertheless, as
      the study may have been underpowered to detect clinically important differences
      in the structural integrity, additional investigations, including the
      optimization of PRP preparation and a larger randomized study powered for healing
      rate, are necessary to further determine the effect of PRP.

PMID- 21737833
TI  - When do rotator cuff repairs fail? Serial ultrasound examination after
      arthroscopic repair of large and massive rotator cuff tears.
AB  - BACKGROUND: Despite advances in arthroscopic repair of rotator cuff tears,
      recurrent tears after repair of large and massive tears remain a significant
      clinical problem. The primary objective of this study was to define the timing of
      structural failure of surgically repaired large and massive rotator cuff tears by
      serial imaging with ultrasound. The secondary objective of this study was to
      investigate the association between recurrent tears and clinical outcome after
      rotator cuff repair. HYPOTHESIS: Recurrent tear after arthroscopic repair of
      large rotator cuff tears is more likely to occur late (>3 months) in the
      postoperative period and will be associated with inferior clinical outcome
      scores. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Twenty-two
      consecutive patients with large (>3 cm) rotator cuff tears underwent arthroscopic
      repair with a standardized technique. Serial ultrasound examinations were
      performed at 2 days, 2 weeks, 6 weeks, 3 months, 6 months, 12 months, and 24
      months after surgery. Western Ontario Rotator Cuff (WORC) Index scores were also
      collected at these time points. RESULTS: Nine (41%) of the 22 arthroscopically
      repaired rotator cuff tears demonstrated recurrent tears. Seven of the 9 retears
      occurred within 3 months of surgery, and the other 2 occurred between 3 and 6
      months. No retears occurred after 6 months. At 24-month follow-up, WORC scores
      favoring intact rotator cuffs over retears approached statistical significance
      (mean WORC intact 123.9 vs retear 659.8; P = .07). CONCLUSION: Recurrent rotator
      cuff tears are not uncommon after arthroscopic repair of large and massive tears.
      These recurrent tears appear to occur more frequently in the early postoperative
      period (within the first 3 months) and are associated with inferior clinical
      outcomes.

PMID- 21737834
TI  - In vivo shoulder function after surgical repair of a torn rotator cuff:
      glenohumeral joint mechanics, shoulder strength, clinical outcomes, and their
      interaction.
AB  - BACKGROUND: Surgical repair of a torn rotator cuff is based on the belief that
      repairing the tear is necessary to restore normal glenohumeral joint (GHJ)
      mechanics and achieve a satisfactory clinical outcome. HYPOTHESIS: Dynamic joint
      function is not completely restored by rotator cuff repair, thus compromising
      shoulder function and potentially leading to long-term disability. STUDY DESIGN:
      Controlled laboratory study and Case series; Level of evidence, 4. METHODS:
      Twenty-one rotator cuff patients and 35 control participants enrolled in the
      study. Biplane radiographic images were acquired bilaterally from each patient
      during coronal-plane abduction. Rotator cuff patients were tested at 3, 12, and
      24 months after repair of a supraspinatus tendon tear. Control participants were
      tested once. Glenohumeral joint kinematics and joint contact patterns were
      accurately determined from the biplane radiographic images. Isometric shoulder
      strength and patient-reported outcomes were measured at each time point.
      Ultrasound imaging assessed rotator cuff integrity at 24 months after surgery.
      RESULTS: Twenty of 21 rotator cuff repairs appeared intact at 24 months after
      surgery. The humerus of the patients' repaired shoulder was positioned more
      superiorly on the glenoid than both the patients' contralateral shoulder and the
      dominant shoulder of control participants. Patient-reported outcomes improved
      significantly over time. Shoulder strength also increased over time, although
      strength deficits persisted at 24 months for most patients. Changes over time in
      GHJ mechanics were not detected for either the rotator cuff patients' repaired or
      contralateral shoulders. Clinical outcome was associated with shoulder strength
      but not GHJ mechanics. CONCLUSION: Surgical repair of an isolated supraspinatus
      tear may be sufficient to keep the torn rotator cuff intact and achieve
      satisfactory patient-reported outcomes, but GHJ mechanics and shoulder strength
      are not fully restored with current repair techniques. CLINICAL RELEVANCE: The
      study suggests that current surgical repair techniques may be effective for
      reducing pain but have not yet been optimized for restoring long-term shoulder
      function.

PMID- 21737835
TI  - Prevalence of Jumper's knee among nonelite athletes from different sports: a
      cross-sectional survey.
AB  - BACKGROUND: The prevalence of jumper's knee among nonelite athletes from
      different sports is unknown. PURPOSE: This study was undertaken to determine the
      prevalence of jumper's knee in nonelite athletes from different sports and to
      determine potential risk factors for jumper's knee. DESIGN: Cohort study
      (prevalence); Level of evidence, 2. METHODS: The authors interviewed 891 male and
      female nonelite athletes from 7 popular sports in The Netherlands: basketball,
      volleyball, handball, korfball, soccer, field hockey, and track and field. Using
      a specially developed questionnaire, information was obtained about individual
      characteristics (age, height, and weight), training background, previous and
      actual knee problems, and the VISA-P (Victorian Institute of Sport Assessment
      Patella) score. RESULTS: The overall prevalence of current jumper's knee was 8.5%
      (78 of 891 athletes), showing a significant difference between sports with
      different loading characteristics. Prevalence was highest among volleyball
      players (14.4%) and lowest among soccer players (2.5%); it was significantly
      higher among male athletes (51 of 502 [10.2%]) than female athletes (25 of 389
      [6.4%]) (chi(2) = 3.91, P = .048). The mean duration of symptoms was 18.9 months
      (standard deviation [SD], 21.6; median value, 12.0; range, 2.0-59.8). The mean
      VISA-P score of the athletes with jumper's knee was 71.4 (SD, 13.8). Athletes
      with jumper's knee were significantly younger, taller, and heavier than those
      without jumper's knee. CONCLUSION: Prevalence of jumper's knee is high among
      nonelite athletes and varies between 14.4% and 2.5% for different sports.
      Jumper's knee is almost twice as common among male nonelite athletes compared
      with female athletes. Different sport-specific loading characteristics of the
      knee extensor apparatus, a younger age, a taller body stature, and higher body
      weight seem to be risk factors associated with patellar tendinopathy.

PMID- 21737836
TI  - Results of arthroscopic repair of type II superior labral anterior posterior
      lesions in overhead athletes: assessment of return to preinjury playing level and
      satisfaction.
AB  - BACKGROUND: The majority of the literature on surgical outcomes of superior
      labral anterior posterior (SLAP) repairs has focused on short-term follow-up of 1
      to 2 years, not allowing adequate time for full rehabilitation and return to
      maximum level of competition for all types of athletes. Also, previous studies
      have concentrated on using questionnaires that primarily evaluate patients'
      activities of daily living, which do not focus on sport-specific performance.
      PURPOSE: To determine the midterm results of type II SLAP repairs in overhead
      athletes, focusing primarily on athletic performance as well as activities of
      daily living. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A
      retrospective review of 30 overhead athletes, who underwent an arthroscopic
      superior labral repair for a symptomatic type II SLAP tear between 2002 and 2007,
      was performed. Our study population included 22 male and 8 female patients with a
      mean age at the time of surgery of 24 years. Twenty-one patients participated in
      baseball or softball, and the remainder of patients were involved in javelin
      throwing or tennis. The average follow-up was 3.5 years. The outcome of treatment
      was evaluated using the American Shoulder and Elbow Society (ASES) scoring
      system, assessing activities of daily living, and the Kerlan-Jobe Orthopaedic
      Clinic Shoulder and Elbow (KJOC) score, assessing sport-specific performance. In
      addition, the length of time to return to sport and the degree of successful
      performance were evaluated. RESULTS: Repairs resulted in ASES scores comparable
      with those from prior published studies (average ASES score, 87.9). The KJOC
      score averaged 73.6. The athletes' perception was that they returned to
      approximately 84.1% of their preinjury level of function with a mean time to
      return to play of 11.7 months. There was a significant drop in the ASES to KJOC
      score for the baseball/softball players (87.9 +/- 14.94 and 72 +/- 19.24,
      respectively; P = .006). Patients reported an overall satisfaction rate of 93.3%
      with the procedure, with the majority being very satisfied. CONCLUSION:
      Arthroscopic SLAP repairs show excellent results and a high rate of overall
      satisfaction; however, the outcomes are less reliable in throwers. The KJOC score
      provides a more stringent assessment of overhead athletes' function after SLAP
      repair than the ASES score. Our findings also indicate that SLAP repairs lead to
      improved shoulder function during routine daily activities but that consistent
      return to elite throwing sports may still remain somewhat problematic.

PMID- 21737837
TI  - Comparison of inside-out and all-inside techniques for the repair of isolated
      meniscal tears: a systematic review.
AB  - BACKGROUND: Arthroscopic meniscal repair techniques are continuing to evolve.
      Most studies to date comparing the healing rate of inside-out to all-inside
      meniscal repair techniques are confounded by associated anterior cruciate
      ligament reconstruction or deficiency. PURPOSE: This review was conducted to
      compare the effectiveness and complications of the inside-out repair technique to
      that of the all-inside repair technique in isolated unstable peripheral
      longitudinal ("bucket-handle") meniscal tears. STUDY DESIGN: Systematic review.
      METHODS: Computerized keyword searches of MEDLINE, EMBASE, CINAHL, ACP Journal
      Club, the Cochrane Central Register of Controlled Trials, and the Cochrane
      Database of Systematic Reviews were performed. Two reviewers independently
      performed searches and article reduction. Studies that included stratified data
      for isolated unstable longitudinal meniscal tears in stable knees, repaired with
      either an inside-out or all-inside repair technique, were selected. Data on
      clinical failure, subjective outcome measures, and complications were summarized.
      RESULTS: Nineteen studies included data specific to isolated meniscal tears. The
      rate of clinical failure was 17% for inside-out repairs and 19% for all-inside
      repairs. Lysholm scores and Tegner activity scores were similar between the 2
      repair methods (87.8 vs 90.2 and 5.6 vs 5.5, respectively). The prevalence of
      nerve injury/irritation was higher with the inside-out technique (9% vs 2%). All
      inside techniques had a higher rate of local soft tissue irritation, swelling,
      and implant migration or breakage. The use of older generation, rigid, all-inside
      implants is associated with chondral injury. CONCLUSION: There are no differences
      in clinical failure rate or subjective outcome between inside-out and all-inside
      meniscus repair techniques. Complications are associated with both techniques.
      More nerve symptoms are associated with the inside-out repair and more implant
      related complications are associated with the all-inside technique. CLINICAL
      RELEVANCE: Rates of structural healing and complications are comparable for
      inside-out and all-inside repair techniques for isolated meniscal injury.
      Differences in observed healing rates after meniscal repair may be more dependent
      on tear pattern and associated anterior cruciate ligament reconstruction rather
      than an inside-out versus all-inside surgical approach.

PMID- 21737838
TI  - Maintaining confidentiality in prospective studies: anonymous repeated
      measurements via email (ARME) procedure.
AB  - Respecting and protecting the confidentiality of data and the privacy of
      individuals regarding the information that they have given as participants in a
      research project is a cornerstone of complying with accepted research standards.
      However, in longitudinal studies, establishing and maintaining privacy is often
      challenging because of the necessity of repeated contact with participants. A
      novel internet-based solution is introduced here, which maintains privacy while
      at the same time ensures linkage of data to individual participants in a repeated
      measures design. With the use of the anonymous repeated measurements via email
      (ARME) procedure, two separate one-way communication systems are established
      through ad hoc email accounts and a secure study website. Strengths and
      limitations of the approach are discussed.

PMID- 21737839
TI  - Academic freedom and global health.
AB  - There is a tension between the preservation of academic freedom and the economic
      context in which the university currently finds itself. This tension embodies
      serious threats to global health as a result of three overlapping phenomena which
      impede the production and diffusion of valuable knowledge about health. These
      phenomena, the privatisation, commercialisation and instrumentalisation of
      knowledge are identified and examined in this paper in relation to human rights
      and international morality.

PMID- 21737840
TI  - Diverse roles of RNA polymerase II-associated factor 1 complex in different
      subpathways of nucleotide excision repair.
AB  - Transcription-coupled repair (TCR) and global genomic repair (GGR) are two
      pathways of nucleotide excision repair (NER). In Saccharomyces cerevisiae, Rad26
      is important but not absolutely required for TCR. Rpb4, a nonessential RNA
      polymerase II (Pol II) subunit that forms a subcomplex with Rpb7, and the Spt4
      Spt5 complex, a transcription elongation factor, have been shown to suppress
      Rad26-independent TCR. The Pol II-associated factor 1 complex (Paf1C) has been
      shown to function in transcription elongation, 3'-processing of mRNAs, and
      posttranslational modification of histones. Here we show that Paf1C plays a
      marginal role in facilitating Rad26-dependent TCR but significantly suppresses
      Rad26-independent TCR. The suppression of Rad26-independent TCR is achieved by
      cooperating with Spt4-Spt5. We propose a model that, in the absence of Rad26, a
      lesion is "locked" in the active center of a Pol II elongation complex, which is
      stabilized by the coordinated interactions of Rpb4-Rpb7, Spt4-Spt5, and Paf1C
      with each other and with the core Pol II. We also found that Paf1C facilitates
      GGR, especially in internucleosomal linker regions. The facilitation of GGR is
      achieved through enabling monoubiquitination of histone H2B lysine 123 by Bre1,
      which in turn permits di- and trimethylation of histone H3 lysine 79 by Dot1. To
      our best knowledge, among the NER-modulating factors documented so far, Paf1C
      appears to have the most diverse functions in different NER pathways or
      subpathways.

PMID- 21737841
TI  - Lipid raft endocytosis and exosomal transport facilitate extracellular
      trafficking of annexin A2.
AB  - Annexin A2 (AnxA2), a Ca(2+)-dependent phospholipid-binding protein, is known to
      associate with the plasma membrane and the endosomal system. Within the plasma
      membrane, AnxA2 associates in a Ca(2+) dependent manner with cholesterol-rich
      lipid raft microdomains. Here, we show that the association of AnxA2 with the
      lipid rafts is influenced not only by intracellular levels of Ca(2+) but also by
      N-terminal phosphorylation at tyrosine 23. Binding of AnxA2 to the lipid rafts is
      followed by the transport along the endocytic pathway to be associated with the
      intralumenal vesicles of the multivesicular endosomes. AnxA2-containing
      multivesicular endosomes fuse directly with the plasma membrane resulting in the
      release of the intralumenal vesicles into the extracellular environment, which
      facilitates the exogenous transfer of AnxA2 from one cell to another. Treatment
      with Ca(2+) ionophore triggers the association of AnxA2 with the specialized
      microdomains in the exosomal membrane that possess raft-like characteristics.
      Phosphorylation at Tyr-23 is also important for the localization of AnxA2 to the
      exosomal membranes. These results suggest that AnxA2 is trafficked from the
      plasma membrane rafts and is selectively incorporated into the lumenal membranes
      of the endosomes to escape the endosomal degradation pathway. The Ca(2+)
      dependent exosomal transport constitutes a novel pathway of extracellular
      transport of AnxA2.

PMID- 21737842
TI  - HIV-1 nucleocapsid protein increases strand transfer recombination by promoting
      dimeric G-quartet formation.
AB  - A preferred site for HIV-1 recombination was identified in vivo and in vitro
      surrounding the beginning of the HIV-1 gag gene. This G-rich gag hotspot for
      recombination contains three evenly spaced G-runs that stalled reverse
      transcriptase. Disruption of the G-runs suppressed both the associated pausing
      and strand transfer in vitro. Significantly, this same gag sequence was able to
      fold into a G-quartet monomer, dimer, and tetramer, depending on the cations
      employed. The pause band at the G-run (nucleotide (nt) 405-409), which was
      predicted to be involved in forming a G-quartet monomer, diminished with
      increased HIV-1 nucleocapsid (NC) protein. More NC induced stronger pauses at
      other G-runs (nt 363-367 and nt 382-384), a region that forms a G-quartet dimer,
      adhering the two RNA templates. We hypothesized that NC induces the unfolding of
      the monomeric G-quartet but stabilizes the dimeric interaction. We tested this by
      inserting a known G-quartet formation sequence, 5'-(UGGGGU)(4)-3', into a
      relatively structure-free template from the HIV-1 pol gene. Strand transfer
      assays were performed with cations that either encourage (K(+)) or discourage
      (Li(+)) G-quartet formation with or without NC. Strikingly, a G-quartet monomer
      was observed without NC, whereas a G-quartet dimer was observed with NC, both
      only in the presence of K(+). Moreover, the transfer efficiency of the dimerized
      template (with K(+) and NC) reached about 90%, approximately 2.5-fold of that of
      the non-dimerized template. Evidently, template dimerization induced by NC
      creates a proximity effect, leading to the unique high peak of transfer at the
      gag recombination hotspot.

PMID- 21737843
TI  - Oligomeric interactions of sarcolipin and the Ca-ATPase.
AB  - We have detected directly the interactions of sarcolipin (SLN) and the
      sarcoplasmic reticulum Ca-ATPase (SERCA) by measuring fluorescence resonance
      energy transfer (FRET) between fusion proteins labeled with cyan fluorescent
      protein (donor) and yellow fluorescent protein (acceptor). SLN is a membrane
      protein that helps control contractility by regulating SERCA activity in fast
      twitch and atrial muscle. Here we used FRET microscopy and spectroscopy with
      baculovirus expression in insect cells to provide direct evidence for: 1)
      oligomerization of SLN and 2) regulatory complex formation between SLN and the
      fast-twitch muscle Ca-ATPase (SERCA1a isoform). FRET experiments demonstrated
      that SLN monomers self-associate into dimers and higher order oligomers in the
      absence of SERCA, and that SLN monomers also bind to SERCA monomers in a 1:1
      binary complex when the two proteins are coexpressed. FRET experiments further
      demonstrated that the binding affinity of SLN for itself is similar to that for
      SERCA. Mutating SLN residue isoleucine-17 to alanine (I17A) decreased the binding
      affinity of SLN self-association and converted higher order oligomers into
      monomers and dimers. The I17A mutation also decreased SLN binding affinity for
      SERCA but maintained 1:1 stoichiometry in the regulatory complex. Thus,
      isoleucine-17 plays dual roles in determining the distribution of SLN homo
      oligomers and stabilizing the formation of SERCA-SLN heterodimers. FRET results
      for SLN self-association were supported by the effects of SLN expression in
      bacterial cells. We propose that SLN exists as multiple molecular species in
      muscle, including SERCA-free (monomer, dimer, oligomer) and SERCA-bound
      (heterodimer), with transmembrane zipper residues of SLN serving to stabilize
      oligomeric interactions.

PMID- 21737844
TI  - A knowledge discovery and reuse pipeline for information extraction in clinical
      notes.
AB  - OBJECTIVE: Information extraction and classification of clinical data are current
      challenges in natural language processing. This paper presents a cascaded method
      to deal with three different extractions and classifications in clinical data:
      concept annotation, assertion classification and relation classification.
      MATERIALS AND METHODS: A pipeline system was developed for clinical natural
      language processing that includes a proofreading process, with gold-standard
      reflexive validation and correction. The information extraction system is a
      combination of a machine learning approach and a rule-based approach. The outputs
      of this system are used for evaluation in all three tiers of the fourth i2b2/VA
      shared-task and workshop challenge. RESULTS: Overall concept classification
      attained an F-score of 83.3% against a baseline of 77.0%, the optimal F-score for
      assertions about the concepts was 92.4% and relation classifier attained 72.6%
      for relationships between clinical concepts against a baseline of 71.0%. Micro
      average results for the challenge test set were 81.79%, 91.90% and 70.18%,
      respectively. DISCUSSION: The challenge in the multi-task test requires a
      distribution of time and work load for each individual task so that the overall
      performance evaluation on all three tasks would be more informative rather than
      treating each task assessment as independent. The simplicity of the model
      developed in this work should be contrasted with the very large feature space of
      other participants in the challenge who only achieved slightly better
      performance. There is a need to charge a penalty against the complexity of a
      model as defined in message minimalisation theory when comparing results.
      CONCLUSION: A complete pipeline system for constructing language processing
      models that can be used to process multiple practical detection tasks of language
      structures of clinical records is presented.

PMID- 21737845
TI  - Cardiac survival after pre-emptive coronary angiography in transplant patients
      and those awaiting transplantation.
AB  - BACKGROUND AND OBJECTIVES: Recent interest has focused on wait listing patients
      without pretreating coronary artery disease to expedite transplantation. Our
      practice is to offer coronary revascularization before transplantation if
      indicated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between 2006 and 2009,
      657 patients (427 men, 230 women; ages, 56.5 +/- 9.94 years) underwent
      pretransplant assessment with coronary angiography. 573 of 657 (87.2%) patients
      were wait listed; 247 of 573 (43.1%) patients were transplanted during the follow
      up period, 30.09 +/- 11.67 months. RESULTS: Patient survival for those not wait
      listed was poor, 83.2% and 45.7% at 1 and 3 years, respectively. In wait-listed
      patients, survival was 98.9% and 95.3% at 1 and 3 years, respectively. 184 of 657
      (28.0%) patients were offered revascularization. Survival in patients (n = 16)
      declining revascularization was poor: 75% survived 1 year and 37.1% survived 3
      years. Patients undergoing revascularization followed by transplantation (n = 51)
      had a 98.0% and 88.4% cardiac event-free survival at 1 and 3 years, respectively.
      Cardiac event-free survival for patients revascularized and awaiting deceased
      donor transplantation was similar: 94.0% and 90.0% at 1 and 3 years,
      respectively. CONCLUSIONS: Our data suggest pre-emptive coronary
      revascularization is not only associated with excellent survival rates in
      patients subsequently transplanted, but also in those patients waiting on
      dialysis for a deceased donor transplant.

PMID- 21737846
TI  - An update on the changing epidemiology and metabolic risk factors in pediatric
      kidney stone disease.
AB  - Nephrolithiasis in children is a painful and costly disease that may also have
      detrimental long-term effects on kidney function. Recent data provide evidence
      that the incidence of nephrolithiasis in children is rising. Children who are
      white, female, and adolescent seem to have the highest risk for forming
      symptomatic kidney stones. Although the reasons for the rising incidence and
      demographic discrepancies in pediatric nephrolithiasis are not yet clear, recent
      investigations into urine chemistry provide clues regarding predisposing
      metabolic risk factors. As more data emerge regarding epidemiologic and metabolic
      characteristics of pediatric kidney stone formers, we hope to gain a better
      understanding of the causes of kidney stone disease and, ultimately, provide
      better strategies for stone prevention in children.

PMID- 21737847
TI  - The spectrum of infections in catheter-dependent hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Catheter-dependent hemodialysis patients may develop
      access-related and nonaccess-related infections that may be managed in the
      outpatient arena or in the hospital. The goal of this study was to quantify
      infections in such patients, to characterize their clinical presentations, and to
      evaluate factors determining need for hospitalization. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We collected prospective data on the clinical
      management of catheter-dependent hemodialysis patients with suspected infection
      at a large dialysis center. We documented the presenting symptoms, type of
      infection, pathogen, and whether hospitalization occurred. RESULTS: An infection
      was suspected in 305 separate cases and confirmed in 88%. The 268 diagnosed
      infections included catheter-related bacteremia (69%), another access-related
      infection (19%), and nonaccess-related infection (12%). The overall frequency of
      infection was 4.62 per 1000 catheter-days. Hospitalization occurred in 37% of all
      infections, but it varied greatly (72% for nonaccess-related infection, 34% for
      catheter-related bacteremia, and 4% for exit-site infection). Among patients with
      catheter-related bacteremia, the likelihood of hospitalization varied by
      pathogen, being 53% for Staphylococcus aureus, 30% for Enterococcus, 23% for
      Staphylococcus epidermidis, and 17% for gram-negative rods (P < 0.001). The
      likelihood of hospitalization was not associated with age, gender, or diabetes.
      Fever was a presenting symptom in only 47% of cases of catheter-related
      bacteremia. CONCLUSIONS: Catheter-dependent patients have a high burden of
      infection. It is important to evaluate patients with suspected infection for
      various access-related and nonaccess-related infections. A low threshold is
      indicated for suspecting catheter-related bacteremia because the patients
      frequently present without fever.

PMID- 21737848
TI  - Oxalate nephropathy associated with chronic pancreatitis.
AB  - BACKGROUND AND OBJECTIVES: Enteric overabsorption of oxalate may lead to
      hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to
      chronic pancreatitis is a rare and poorly described condition precluding early
      recognition and treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      collected the clinical characteristics, treatment, and renal outcome of 12
      patients with chronic pancreatitis-associated AON followed in four French renal
      units. RESULTS: Before AON, mild to moderate chronic kidney disease was present
      in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic
      drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation,
      pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation,
      calcification, or pseudocyst. Renal findings consisted of rapidly progressive
      renal failure with tubulointerstitial profile. Acute modification of glomerular
      filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary
      oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5
      mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly
      suggestive of oxalate crystals, with tubular necrosis and interstitial
      inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme
      supplementation, oral calcium intake, and an oxalate-free diet in all patients
      and renal replacement therapy in five patients. After a median follow-up of 7
      months, three of 12 patients reached end-stage renal disease. CONCLUSION: AON is
      an under-recognized severe crystal-induced renal disease with features of
      tubulointerstitial nephritis that may occur in patients with a long history of
      chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering
      factors should be prevented.

PMID- 21737849
TI  - Age-specific association of reduced estimated glomerular filtration rate and
      albuminuria with all-cause mortality.
AB  - BACKGROUND AND OBJECTIVES: It has been suggested that reduced estimated GFR
      (eGFR) among older adults does not necessarily reflect a pathologic phenomenon.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined the association
      between eGFR and albumin-to-creatinine ratio (ACR) and all-cause mortality
      stratified by age (45 to 59.9, 60 to 69.9, 70 to 79.9, and >=80 years) among
      24,350 U.S. adults in the population-based REasons for Geographic and Racial
      Differences in Stroke (REGARDS) study. A spot urine sample was used to calculate
      ACR, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
      was used to calculate eGFR. All-cause mortality was assessed over a median follow
      up of 4.5 years. RESULTS: Among participants >=80 years of age (n = 1669), the
      age, race, gender, and geographic region of residence adjusted hazard ratios (95%
      confidence intervals) for mortality associated with eGFR levels of 45 to 59.9 and
      <45 ml/min per 1.73 m(2), versus >=60 ml/min per 1.73 m(2), were 1.6 (1.3 - 2.1)
      and 2.2 (1.7 - 2.9), respectively. Also, among participants >=80 years of age,
      the hazard ratios for mortality associated with ACR levels of 10 to 29.9, 30 to
      299.9, and >=300 mg/g, versus <10 mg/g, were 1.7 (1.3 - 2.1), 2.5 (1.9 - 3.3),
      and 5.1 (3.6 - 7.4), respectively. These associations were present after further
      multivariable adjustment and within the younger age groupings studied.
      CONCLUSIONS: These data suggest that reduced eGFR and albuminuria confer an
      increased risk for mortality in all age groups, including adults >=80 years of
      age.

PMID- 21737850
TI  - Neurocognitive functioning of children and adolescents with mild-to-moderate
      chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Few data exist on the neurocognitive functioning of
      children with mild-to-moderate chronic kidney disease (CKD). The primary
      objectives of this paper are (1) to determine the neurocognitive status in this
      population and (2) to identify sociodemographic and health-status variables
      associated with neurocognitive functioning. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This was a cross-sectional study of 368 children, aged 6 to 16
      years, from the Chronic Kidney Disease in Children (CKiD) cohort. Median iGFR was
      43 ml/min per 1.73 m(2), and the median duration of CKD was 8.0 years.
      Approximately 26% had underlying glomerular disease. Measures of intelligence,
      academic achievement, attention regulation, and executive functioning were
      obtained at study entry. The prevalence of neurocognitive deficits was determined
      by comparing participant scores on each measure of neurocognitive functioning
      with normative data. The association between hypothesized predictors of
      neurocognitive dysfunction was evaluated using multivariate regression analyses.
      RESULTS: Neurocognitive functioning was within the average range for the entire
      group; however, 21% to 40% of participants scored at least one SD below the mean
      on measures of intelligence quotient (IQ), academic achievement, attention
      regulation, or executive functioning. Higher iohexol-based GFR (iGFR) predicted a
      lesser risk for poor performance on measures of executive function. Participants
      having elevated proteinuria (i.e., urine protein/creatinine >2) scored lower on
      verbal IQ, full-scale IQ, and attention variability than those without elevated
      proteinuria. CONCLUSIONS: Whereas most children with mild-to-moderate CKD have no
      major neurocognitive deficits, a substantial percentage did show neurocognitive
      dysfunction that places them at risk for poor long-term educational and
      occupational outcomes.

PMID- 21737851
TI  - Outcomes of arteriovenous fistula creation after the Fistula First Initiative.
AB  - BACKGROUND AND OBJECTIVES: The arteriovenous fistula (AVF) is the preferred
      hemodialysis access, but AVF-failure rate is high, and complications from AVF
      placement are rarely reported. There is no clear consensus on predictors of AVF
      patency. This study determined AVF outcomes and patency predictors at Mayo Clinic
      Rochester following the Fistula First Initiative. DESIGN, SETTING, PARTICIPANTS,
      & MEASUREMENTS: A retrospective cohort study of AVFs placed at Mayo Clinic from
      January 2006 through December 2008 was performed. The AVF placement-associated
      primary and secondary failure rates, complications, interventions, and
      hospitalizations were examined. Kaplan-Meier survival curves and Cox proportional
      hazard models were used to determine primary and secondary patency and associated
      predictors. RESULTS: During this time frame, 317 AVFs were placed in 293
      individual patients. The primary failure rate was 37.1% after excluding patients
      not initiated on hemodialysis during follow-up (n = 38) or those with
      indeterminate outcome (37 lost to follow-up; six died; two transplanted). Of
      usable AVFs, 11.4% later failed. AVF creation incurred complications and
      hospitalization in 21.2% and 12.3% of patients, respectively. The risk for
      reduced primary patency was increased by diabetes (HR, 1.54; 95% CI, 1.14 to
      2.07); the risk for reduced primary and secondary patency was decreased with
      larger arteries (HR, 0.83; 95% CI, 0.73 to 0.94; and HR, 0.69; 95% CI, 0.56 to
      0.84, respectively). CONCLUSIONS: Primary failure remains a major issue in the
      post-Fistula First era. Complications from AVF placement must be considered when
      planning AVF placement. Our data demonstrate that artery size is the main
      predictor of AVF patency.

PMID- 21737852
TI  - Relative performance of the MDRD and CKD-EPI equations for estimating glomerular
      filtration rate among patients with varied clinical presentations.
AB  - BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equation was developed using both CKD and non-CKD patients to potentially replace
      the Modification of Diet in Renal Disease (MDRD) equation that was derived with
      only CKD patients. The objective of our study was to compare the accuracy of the
      MDRD and CKD-EPI equations for estimating GFR in a large group of patients having
      GFR measurements for diverse clinical indications. DESIGN, SETTING, PARTICIPANTS,
      AND MEASUREMENTS: A cross-sectional study was conducted of patients who underwent
      renal function assessment for clinical purposes by simultaneous measurements of
      serum creatinine and estimation of GFR using the MDRD and CKD-EPI equations and
      renal clearance of iothalamate (n = 5238). RESULTS: Bias compared with measured
      GFR (mGFR) varied for each equation depending on clinical presentation. The CKD
      EPI equation demonstrated less bias than the MDRD equation in potential kidney
      donors (-8% versus -18%) and postnephrectomy donors (-7% versus -15%). However,
      the CKD-EPI equation was slightly more biased than the MDRD equation in native
      CKD patients (6% versus 3%), kidney recipients (8% versus 1%), and other organ
      recipients (9% versus 3%). Among potential kidney donors, the CKD-EPI equation
      had higher specificity than the MDRD equation for detecting an mGFR <60 ml/min
      per 1.73 m(2) (98% versus 94%) but lower sensitivity (50% versus 70%).
      CONCLUSIONS: Clinical presentation influences the estimation of GFR from serum
      creatinine, and neither the CKD-EPI nor MDRD equation account for this. Use of
      the CKD-EPI equation misclassifies fewer low-risk patients as having reduced
      mGFR, although it is also less sensitive for detecting mGFR below specific
      threshold values used to define CKD stages.

PMID- 21737853
TI  - Bone microarchitecture in hemodialysis patients assessed by HR-pQCT.
AB  - BACKGROUND AND OBJECTIVES: Dialysis patients are at high risk for low-trauma bone
      fracture. Bone density measurements using dual-energy x-ray absorptiometry (DXA)
      do not reliably differentiate between patients with and without fractures. The
      aim of this study was to identify differences in bone microarchitecture between
      patients with and without a history of fracture using high-resolution peripheral
      quantitative computed tomography (HR-pQCT). DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Seventy-four prevalent hemodialysis patients were recruited for
      measurements of areal bone mineral density (aBMD) by DXA and bone
      microarchitecture by HR-pQCT. Patients with a history of trauma-related fracture
      were excluded. Forty healthy volunteers served as controls. Blood levels of
      parathyroid hormone, vitamin D, and markers of bone turnover were determined.
      RESULTS: Dialysis patients, particularly women, had markedly impaired bone
      microarchitecture. Patients with fractures had significantly reduced cortical and
      trabecular microarchitecture compared with patients without fractures. aBMD
      tended to be lower in patients with fractures, but differences were statistically
      not significant. The strongest determinant of fracture was the HR-pQCT-measured
      trabecular density of the tibia, which also had the highest discriminatory power
      to differentiate patients according to fracture status. Radial DXA had a lower
      discriminatory power than trabecular density. CONCLUSIONS: Bone microarchitecture
      is severely impaired in dialysis patients and even more so in patients with a
      history of fracture. HR-pQCT can identify dialysis patients with a history of low
      trauma fracture.

PMID- 21737854
TI  - Geographic and educational factors and risk of the first peritonitis episode in
      Brazilian Peritoneal Dialysis study (BRAZPD) patients.
AB  - BACKGROUND AND OBJECTIVES: Peritonitis remains as the most frequent cause of
      peritoneal dialysis (PD) failure, impairing patient's outcome. No large
      multicenter study has addressed socioeconomic, educational, and geographic issues
      as peritonitis risk factors in countries with a large geographic area and diverse
      socioeconomic conditions, such as Brazil. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Incident PD patients recruited from 114 dialysis centers and
      reporting to BRAZPD, a multicenter observational study, from December 2004
      through October 2007 were included. Clinical, dialysis-related, demographic, and
      socioeconomic variables were analyzed. Patients were followed up until their
      first peritonitis. Cox proportional model was used to determine independent
      factors associated with peritonitis. RESULTS: In a cumulative follow-up of 2032
      patients during 22.026 patient-months, 474 (23.3%) presented a first peritonitis
      episode. In contrast to earlier findings, PD modality, previous hemodialysis,
      diabetes, gender, age, and family income were not risk predictors. Factors
      independently associated with increased hazard risk were lower educational level,
      non-white race, region where patients live, shorter distance from dialysis
      center, and lower number of patients per center. CONCLUSIONS: Educational level
      and geographic factors as well as race and center size are associated with risk
      for the first peritonitis, independent of socioeconomic status, PD modality, and
      comorbidities.

PMID- 21737855
TI  - Cardiac geometry in children receiving chronic peritoneal dialysis: findings from
      the International Pediatric Peritoneal Dialysis Network (IPPN) registry.
AB  - BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) is an independent
      risk factor and an intermediate end point of dialysis-associated cardiovascular
      comorbidity. We utilized a global pediatric registry to assess the prevalence,
      incidence, and predictors of LVH as well as its evolution in the longitudinal
      follow-up in dialyzed children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Cross-sectional echocardiographic, clinical, and biochemical data were evaluated
      in 507 children on peritoneal dialysis (PD), and longitudinal data were evaluated
      in 128 patients. The 95(th) percentile of LV mass index relative to height age
      was used to define LVH. RESULTS: The overall LVH prevalence was 48.1%. In the
      prospective analysis, the incidence of LVH developing de novo in patients with
      normal baseline LV mass was 29%, and the incidence of regression from LVH to
      normal LV mass 40% per year on PD. Transformation to and regression from
      concentric LV geometry occurred in 36% and 28% of the patients, respectively.
      Hypertension, high body mass index, use of continuous ambulatory peritoneal
      dialysis, renal disease other than hypo/dysplasia, and hyperparathyroidism were
      identified as independent predictors of LVH. The use of renin-angiotensin system
      (RAS) antagonists and high total fluid output (sum of urine and ultrafiltration)
      were protective from concentric geometry. The risk of LVH at 1 year was increased
      by higher systolic BP standard deviation score and reduced in children with renal
      hypo/dysplasia. CONCLUSIONS: Using height-adjusted left ventricular mass index
      reference data, LVH is highly prevalent but less common than previously diagnosed
      in children on PD. Renal hypo/dysplasia is protective from LVH, likely because of
      lower BP and polyuria. Hypertension, fluid overload, and hyperparathyroidism are
      modifiable determinants of LVH.

PMID- 21737856
TI  - Toward a definition of masked hypertension and white-coat hypertension among
      hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Among people with essential hypertension, ambulatory
      BP measurement is superior to BP obtained in the clinic in predicting
      cardiovascular outcomes. In part, this is because it can detect white-coat
      hypertension and masked hypertension. Whether the same is true for hemodialysis
      patients is not known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a
      threshold of 140/80 mmHg for median midweek dialysis-unit BP and 135/85 mmHg for
      44-hour ambulatory BP, we defined four categories of BP: sustained normotension
      (SN), white-coat hypertension (WCH), masked hypertension (MHTN), and sustained
      hypertension (SHTN). RESULTS: Among 355 long-term hemodialysis patients, the
      prevalence of SN was 35%, WCH 15%, MHTN 15%, and SHTN 35%. Over a mean follow-up
      of 29.6 (SD 21.7) months, 102 patients died (29%), yielding a crude mortality
      rate of 121/1000 patient-years. Unadjusted and multivariate-adjusted analyses
      showed increasing all-cause mortality with increasing severity of hypertension
      (unadjusted hazard ratios from SN, WCH, MHTN, SHTN: 1, 1.12, 1.70, 1.80,
      respectively [P for trend < 0.01]; adjusted hazard ratios: 1, 1.30, 1.36, 1.87,
      respectively [P for trend 0.02]). When a predialysis BP threshold of 140/90 mmHg
      was used to classify patients into BP categories, the prevalence of SN was 24%,
      WCH 26%, MHTN 4%, and SHTN 47%. Hazard ratios for mortality were similar when
      compared with median midweek dialysis-unit BP. CONCLUSIONS: As in the essential
      hypertension population, MHTN and WCH have prognostic significance. The
      prognostic value of BP obtained in the dialysis unit can be refined with
      ambulatory BP monitoring.

PMID- 21737857
TI  - Defining left ventricular hypertrophy in children on peritoneal dialysis.
AB  - BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) is an important end
      point of dialysis-associated cardiovascular disease. The objective of this study
      was to evaluate the effect of different pediatric reference systems on the
      estimated prevalence of LVH in children on chronic peritoneal dialysis (CPD).
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Echocardiographic studies in 507
      pediatric CPD patients from neonatal age to 19 years were collected in 55
      pediatric dialysis units around the globe. We compared the prevalence of LVH on
      the basis of the traditional cutoff of left ventricular mass (LVM) index (>38.5
      g/m(2.7)) with three novel definitions of LVH that were recently established in
      healthy pediatric cohorts. RESULTS: Application of the new reference systems
      eliminated the apparently increased prevalence of LVH in young children obtained
      by the traditional fixed LVM index cutoff currently still recommended by
      consensus guidelines. However, substantial differences of LVM distribution
      between the new reference charts resulted in a marked discrepancy in estimated
      LVH prevalence ranging between 27.4% and 51.7%. CONCLUSIONS: Although our
      understanding of the anthropometric determinants of heart size during childhood
      is improving, more consistent normative echocardiographic data from large
      populations of healthy children are required for cardiovascular diagnostics and
      research.

PMID- 21737858
TI  - Is youth smoking responsive to cigarette prices? Evidence from low- and middle
      income countries.
AB  - OBJECTIVE: To estimate the price elasticity of cigarette demand among youth in
      low- and middle-income countries (LMIC). DATA: The Global Youth Tobacco Survey
      was used to obtain data on the smoking behaviour of 315,353 adolescents from 17
      LMIC. DESIGN: Two-part model of cigarette demand with country fixed effects. The
      first part estimates the impact of prices on smoking participation while the
      second part estimates the impact of prices on the number of cigarettes smoked
      among current smokers. Besides controlling for individual characteristics such as
      Age, Gender, Parental Smoking and availability of Pocket Money, the authors
      control for confounding environmental factors such as anti-smoking sentiment, the
      prevalence of cigarette advertising and anti-tobacco media messAges, and ease of
      purchasing cigarettes. All countries in this study are represented with at least
      two observations over time, which allows us to control for unobserved country
      characteristics and/or policies that may influence smoking patterns within
      countries. RESULTS: Cigarette price is an important determinant of smoking. The
      estimated price elasticity of smoking participation is -0.74, and the estimated
      price elasticity of conditional cigarette demand is approximately -1.37. The
      total price elasticity of cigarette demand is -2.11, implying that an increase in
      price of 10% would reduce youth cigarette consumption by 21.1% at the mean.

PMID- 21737859
TI  - Local appendiceal dysbiosis: the missing link between the appendix and ulcerative
      colitis?

PMID- 21737860
TI  - Sound synthesis and evaluation of interactive footsteps and environmental sounds
      rendering for virtual reality applications.
AB  - We propose a system that affords real-time sound synthesis of footsteps on
      different materials. The system is based on microphones, which detect real
      footstep sounds from subjects, from which the ground reaction force (GRF) is
      estimated. Such GRF is used to control a sound synthesis engine based on physical
      models. Two experiments were conducted. In the first experiment, the ability of
      subjects to recognize the surface they were exposed to was assessed. In the
      second experiment, the sound synthesis engine was enhanced with environmental
      sounds. Results show that, in some conditions, adding a soundscape significantly
      improves the recognition of the simulated environment.

PMID- 21737861
TI  - A memory-efficient unified early z-test.
AB  - The Unified Early Z-Test (U-EZT) is proposed to examine the visibility of pixels
      during tile-based rasterization in a mobile 3D graphics processor. U-EZT combines
      the advantages of the Z-max and Z-min EZT algorithms: the Z-max algorithm is
      improved by the independently updatable z-max tiles and the use of mask bits; and
      the Z-min algorithm is improved by reusing the mask bits from the z-max test to
      update the z-min tiles after tile rasterizing. As a result, storage requirements
      are reduced to 3 bits per pixel, and simulations suggest that U-EZT requires 20
      percent to 57 percent less memory bandwidth than previous EZT algorithms.

PMID- 21737862
TI  - Ordered Boolean List (OBL): reducing the footprint for evaluating Boolean
      expressions.
AB  - An Expanded Boolean Expression (EBE) does not contain any XOR or EQUAL operators.
      The occurrence of each variable is a different literal. We provide a linear time
      algorithm that converts an EBE of n literals into a logically equivalent Ordered
      Boolean List (OBL) and show how to use the OBL to evaluate the EBE in n steps and
      O(log log n) space, if the values of the literals are each read once in the order
      prescribed by the OBL. (An evaluation workspace of 5 bits suffices for all EBEs
      of up to six billion literals.) The primary application is the SIMD architecture,
      where the same EBE is evaluated in parallel for different input vectors when
      rendering solid models on the GPU directly from their Constructive Solid Geometry
      (CSG) representation. We compare OBL to the Reduced Ordered Binary Decision
      Diagram (ROBDD) and suggest possible applications of OBL to logic verification
      and to circuit design.

PMID- 21737863
TI  - The role of Hund's coupling in the stabilization of the (0, pi) ordered spin
      density wave state within the minimal two-band model for iron pnictides.
AB  - Spin wave excitations and the stability of the (0, pi) ordered spin density wave
      (SDW) state are investigated within the minimal two-band model for iron pnictides
      including a Hund's coupling term. The SDW state is shown to be stable in two
      distinct doping regimes-for finite hole doping in the lower SDW band for small
      second-neighbour hoppings, and for low electron doping in the upper SDW band for
      comparable first-neighbour and second-neighbour hoppings. In both cases, Hund's
      coupling strongly stabilizes the SDW state due to the generation of additional
      ferromagnetic spin couplings involving the inter-orbital part of the particle
      hole propagator. The spin wave energies for the two-band model are very similar
      to the one-band t-t' Hubbard model results obtained earlier, and are in agreement
      with the findings from inelastic neutron scattering studies of iron pnictides.

PMID- 21737865
TI  - Effects of a perpendicular magnetic field in the dipolar Heisenberg model with
      dominant exchange interaction.
AB  - The effects of a uniform magnetic field on the phase diagram of the dipolar
      Heisenberg model with a dominant antiferromagnetic exchange interaction have been
      investigated. The model consists of a square lattice of classical spin vectors,
      where the spins interact through an antiferromagnetic exchange interaction of
      strength J and a dipole-dipole interaction of strength g. The spins couple to a
      magnetic surface anisotropy of strength kappa and to an applied external magnetic
      field of strength H. The external field is applied perpendicular to the plane of
      the lattice. From extensive Monte Carlo simulations, representative magnetic
      phase diagrams have been determined as a function of the ratios kappa/g and T/g,
      where T is temperature, and at three different ratios of H/g (H/g = 10, 20, 27).
      These results are compared to the previously investigated case of H/g = 0 and to
      analytic calculations for the ground state energies. The nature of the
      equilibrium phases and order of the phase boundaries separating them are
      considered and changes due to the strength of the applied field are highlighted.

PMID- 21737866
TI  - Electronic band structures of graphene nanoribbons with self-passivating edge
      reconstructions.
AB  - Using the nearest-neighbor tight-binding approach we study the electronic band
      structures of graphene nanoribbons with self-passivating edge reconstructions.
      For zigzag ribbons the edge reconstruction moves both the Fermi energy and the
      flat band down by several hundred meV, and the flat band is always found to be
      below the Fermi energy. The states featured by the flat band are shown to be
      mainly localized at the atoms belonging to several lattice lines closest to the
      edges. For armchair ribbons the edge reconstruction strongly modifies the band
      structure in the region close to the Fermi energy, leading to the appearance of a
      band gap even for ribbons which were predicted to be metallic in the model of
      standard armchair edges. The gap widths are, however, strongly different in
      magnitude and behave in different ways regarding the ribbon width.

PMID- 21737867
TI  - Effect of strain on the thermoelectric properties of silicon: an ab initio study.
AB  - On the basis of detailed first-principles calculations the anisotropic
      thermoelectric transport properties of biaxially strained silicon were studied
      with the focus on a possible enhancement of the power factor. Electron as well as
      hole doping was examined in a broad doping and temperature range. In the low
      temperature and low doping regime an enhancement of the power factor was obtained
      for compressive and tensile strain in the electron-doped case, and for
      compressive strain in the hole-doped case. In the thermoelectrically more
      important high temperature and high doping regime a slight enhancement of the
      power factor was only found for the hole-doped case under small biaxial tensile
      strain. The results are discussed in terms of band structure effects. An
      analytical model is presented to understand the fact that the thermopower
      decreases if degenerate bands are energetically lifted due to a strain-induced
      redistribution of states.

PMID- 21737868
TI  - Correlating locations in ipsilateral breast tomosynthesis views using an
      analytical hemispherical compression model.
AB  - To improve cancer detection in mammography, breast examinations usually consist
      of two views per breast. In order to combine information from both views,
      corresponding regions in the views need to be matched. In 3D digital breast
      tomosynthesis (DBT), this may be a difficult and time-consuming task for
      radiologists, because many slices have to be inspected individually. For
      multiview computer-aided detection (CAD) systems, matching corresponding regions
      is an essential step that needs to be automated. In this study, we developed an
      automatic method to quickly estimate corresponding locations in ipsilateral
      tomosynthesis views by applying a spatial transformation. First we match a model
      of a compressed breast to the tomosynthesis view containing a point of interest.
      Then we estimate the location of the corresponding point in the ipsilateral view
      by assuming that this model was decompressed, rotated and compressed again. In
      this study, we use a relatively simple, elastically deformable sphere model to
      obtain an analytical solution for the transformation in a given DBT case. We
      investigate three different methods to match the compression model to the data by
      using automatic segmentation of the pectoral muscle, breast tissue and nipple.
      For validation, we annotated 208 landmarks in both views of a total of 146 imaged
      breasts of 109 different patients and applied our method to each location. The
      best results are obtained by using the centre of gravity of the breast to define
      the central axis of the model, around which the breast is assumed to rotate
      between views. Results show a median 3D distance between the actual location and
      the estimated location of 14.6 mm, a good starting point for a registration
      method or a feature-based local search method to link suspicious regions in a
      multiview CAD system. Approximately half of the estimated locations are at most
      one slice away from the actual location, which makes the method useful as a
      mammographic workstation tool for radiologists to interactively find
      corresponding locations in ipsilateral tomosynthesis views.

PMID- 21737869
TI  - Ordered phases of encapsulated diamondoids into carbon nanotubes.
AB  - Diamondoids are hydrogen-terminated nanosized diamond fragments that are present
      in petroleum crude oil at low concentrations. These fragments are found as
      oligomers of the smallest diamondoid, adamantane (C(10)H(16)). Due to their small
      size, diamondoids can be encapsulated into carbon nanotubes to form linear
      arrangements. We have investigated the encapsulation of diamondoids into single
      walled carbon nanotubes with diameters between 1.0 and 2.2 nm using fully
      atomistic simulations. We performed classical molecular dynamics and energy
      minimizations calculations to determine the most stable configurations. We
      observed molecular ordered phases (e.g. double, triple, 4- and 5-stranded
      helices) for the encapsulation of adamantane, diamantane, and dihydroxy
      diamantane. Our results also indicate that the functionalization of diamantane
      with hydroxyl groups can lead to an improvement on the molecular packing factor
      when compared to non-functionalized compounds. Comparisons to hard-sphere models
      revealed differences, especially when more asymmetrical diamondoids were
      considered. For larger diamondoids (i.e., adamantane tetramers), we have not
      observed long-range ordering but only a tendency to form incomplete helical
      structures. Our calculations predict that thermally stable (at least up to room
      temperature) complex ordered phases of diamondoids can be formed through
      encapsulation into carbon nanotubes.

PMID- 21737870
TI  - Efficient photogeneration of charge carriers in silicon nanowires with a radial
      doping gradient.
AB  - by performing electrodeless time-resolved microwave conductivity measurements,
      the efficiency of charge carrier generation, their mobility, and the decay
      kinetics on photoexcitation were studied in arrays of Si nanowires grown by the
      vapor-liquid-solid mechanism. Large enhancements in the magnitude of the
      photoconductance and charge carrier lifetime are found depending on the
      incorporation of impurities during the growth. They are explained by the internal
      electric field that builds up, due to higher doped sidewalls, as revealed by
      detailed analysis of the nanowire morphology and chemical composition.

PMID- 21737871
TI  - Gas-phase production of gold-decorated silica nanoparticles.
AB  - Gold-decorated silica nanoparticles were synthesized in a two-step process in
      which silica nanoparticles were produced by chemical vapor synthesis using
      tetraethylorthosilicate (TEOS) and subsequently decorated using two different gas
      phase evaporative techniques. Both evaporative processes resulted in gold
      decoration of the silica particles. This study compares the mechanisms of
      particle decoration for a production method in which the gas and particles remain
      cool to a method in which the entire aerosol is heated. Results of transmission
      electron microscopy and visible spectroscopy studies indicate that both methods
      produce particles with similar morphologies and nearly identical absorption
      spectra, with peak absorption at 500-550 nm. A study of the thermal stability of
      the particles using heated-TEM indicates that the gold decoration on the particle
      surface remains stable at temperatures below 900  degrees C, above which the gold
      decoration begins to both evaporate and coalesce.

PMID- 21737872
TI  - Highly efficient fibrous dye-sensitized solar cells based on TiO2 nanotube
      arrays.
AB  - The structure of fibrous dye-sensitized solar cells, which were constructed by a
      TiO(2) nanotube array on Ti wire as the photoanode twisted by a Pt wire counter
      electrode, has been first systematically investigated by accurately controlling
      the thread pitch distance of screwed Pt wire. It has been revealed that the
      thread pitch will strongly influence the photovoltaic performance and kinetic
      processes in fibrous solar cells. The effect of the length of the TiO(2) nanotube
      on cell performance has also been discussed. After optimization, a relatively
      universal optimized thread pitch value of 1 mm for fibrous DSCs has been proved
      and the light-to-electricity conversion efficiency has been remarkably improved
      to 5.84%.

PMID- 21737873
TI  - Quantitative excited state spectroscopy of a single InGaAs quantum dot molecule
      through multi-million-atom electronic structure calculations.
AB  - Atomistic electronic structure calculations are performed to study the coherent
      inter-dot couplings of the electronic states in a single InGaAs quantum dot
      molecule. The experimentally observed excitonic spectrum by Krenner et al (2005)
      Phys. Rev. Lett. 94 057402 is quantitatively reproduced, and the correct energy
      states are identified based on a previously validated atomistic tight binding
      model. The extended devices are represented explicitly in space with 15-million
      atom structures. An excited state spectroscopy technique is applied where the
      externally applied electric field is swept to probe the ladder of the electronic
      energy levels (electron or hole) of one quantum dot through anti-crossings with
      the energy levels of the other quantum dot in a two-quantum-dot molecule. This
      technique can be used to estimate the spatial electron-hole spacing inside the
      quantum dot molecule as well as to reverse engineer quantum dot geometry
      parameters such as the quantum dot separation. Crystal-deformation-induced
      piezoelectric effects have been discussed in the literature as minor
      perturbations lifting degeneracies of the electron excited (P and D) states, thus
      affecting polarization alignment of wavefunction lobes for III-V heterostructures
      such as single InAs/GaAs quantum dots. In contrast, this work demonstrates the
      crucial importance of piezoelectricity to resolve the symmetries and energies of
      the excited states through matching the experimentally measured spectrum in an
      InGaAs quantum dot molecule under the influence of an electric field. Both linear
      and quadratic piezoelectric effects are studied for the first time for a quantum
      dot molecule and demonstrated to be indeed important. The net piezoelectric
      contribution is found to be critical in determining the correct energy spectrum,
      which is in contrast to recent studies reporting vanishing net piezoelectric
      contributions.

PMID- 21737874
TI  - Shape control of cadmium hydroxides (Cd(OH)2) sensitive to pH quenching depth and
      massive production of CdSe nanocrystals by their chemical transformation.
AB  - This study demonstrates that the structure of cadmium hydroxides (Cd(OH)(2))
      precipitated from a basic cadmium nitrate solution can be finely controlled by
      adjusting the pH of the precursor solution. The synthesis process involves only
      pouring the saturated solution into pure water to quench the pH and the total
      process is finished within 30 s. At a shallow pH quenching, the unstable
      nanoparticles turned into microparticles via a ripening process. Cd(OH)(2) was
      precipitated in the form of one-dimensional nanowires and then two-dimensional
      plates as the pH quenching was increased. At a large pH quenching, porous
      aggregates of Cd(OH)(2) were obtained due to the too fast precipitation. The
      ultrafine Cd(OH)(2) nanowires were readily transformed into CdSe chain-like
      nanocrystals. The transformation was quick and gave 100% yield, facilitating
      massive production of CdSe nanocrystals in an aqueous condition. The Cd(OH)(2)
      nanowires were directly grown on Si nanowires and transformed into CdSe chain
      like nanocrystals, decorating the surface of each Si nanowire.

PMID- 21737875
TI  - Junction fabrication by shadow evaporation without a suspended bridge.
AB  - We present a novel shadow evaporation technique for the realization of junctions
      and capacitors. The design by e-beam lithography of strongly asymmetric undercuts
      on a bilayer resist enables in situ fabrication of junctions and capacitors
      without the use of the well-known suspended bridge (Dolan 1977 Appl. Phys. Lett.
      31 337-9). The absence of bridges increases the mechanical robustness of the
      resist mask as well as the accessible range of the junction size, from 10(-2)
      um(2) to more than 10(4) um(2). We have fabricated Al/AlO(x)/Al Josephson
      junctions, phase qubit and capacitors using a 100 kV e-beam writer. Although this
      high voltage enables a precise control of the undercut, implementation using a
      conventional 20 kV e-beam is also discussed. The phase qubit coherence times,
      extracted from spectroscopy resonance width, Rabi and Ramsey oscillation decays
      and energy relaxation measurements, are longer than the ones obtained in our
      previous samples realized by standard techniques. These results demonstrate the
      high quality of the junction obtained by this bridge-free technique.

PMID- 21737876
TI  - Human ovarian carcinoma-associated  mesenchymal stem cells regulate  cancer stem
      cells and tumorigenesis  via altered BMP production.
AB  - Accumulating evidence suggests that mesenchymal stem cells (MSCs) are recruited
      to the tumor microenvironment; however, controversy exists regarding their role
      in solid tumors. In this study, we identified and confirmed the presence of
      carcinoma-associated MSCs (CA-MSCs) in the majority of human ovarian tumor
      samples that we analyzed. These CA-MSCs had a normal morphologic appearance, a
      normal karyotype, and were nontumorigenic. CA-MSCs were multipotent with capacity
      for differentiating into adipose, cartilage, and bone. When combined with tumor
      cells in vivo, CA-MSCs promoted tumor growth more effectively than did control
      MSCs. In vitro and in vivo studies suggested that CA-MSCs promoted tumor growth
      by increasing the number of cancer stem cells. Although CA-MSCs expressed
      traditional MSCs markers, they had an expression profile distinct from that of
      MSCs from healthy individuals, including increased expression of BMP2, BMP4, and
      BMP6. Importantly, BMP2 treatment in vitro mimicked the effects of CA-MSCs on
      cancer stem cells, while inhibiting BMP signaling in vitro and in vivo partly
      abrogated MSC-promoted tumor growth. Taken together, our data suggest that MSCs
      in the ovarian tumor microenvironment have an expression profile that promotes
      tumorigenesis and that BMP inhibition may be an effective therapeutic approach
      for ovarian cancer.

PMID- 21737877
TI  - Modulation of subthalamic T-type Ca(2+)  channels remedies locomotor deficits  in
      a rat model of Parkinson disease.
AB  - An increase in neuronal burst activities in the subthalamic nucleus (STN) is a
      well-documented electrophysiological feature of Parkinson disease (PD). However,
      the causal relationship between subthalamic bursts and PD symptoms and the ionic
      mechanisms underlying the bursts remain to be established. Here, we have shown
      that T-type Ca(2+) channels are necessary for subthalamic burst firing and that
      pharmacological blockade of T-type Ca(2+) channels reduces motor deficits in a
      rat model of PD. Ni(2+), mibefradil, NNC 55-0396, and efonidipine, which
      inhibited T-type Ca(2+) currents in acutely dissociated STN neurons, but not
      Cd(2+) and nifedipine, which preferentially inhibited L-type or the other non-T
      type Ca(2+) currents, effectively diminished burst activity in STN slices.
      Topical administration of inhibitors of T-type Ca(2+) channels decreased in vivo
      STN burst activity and dramatically reduced the locomotor deficits in a rat model
      of PD. Cd(2+) and nifedipine showed no such electrophysiological and behavioral
      effects. While low-frequency deep brain stimulation (DBS) has been considered
      ineffective in PD, we found that lengthening the duration of the low-frequency
      depolarizing pulse effectively improved behavioral measures of locomotion in the
      rat model of PD, presumably by decreasing the availability of T-type Ca(2+)
      channels. We therefore conclude that modulation of subthalamic T-type Ca(2+)
      currents and consequent burst discharges may provide new strategies for the
      treatment of PD.

PMID- 21737878
TI  - Retinoic acid induces homing of  protective T and B cells to the gut after 
      subcutaneous immunization in mice.
AB  - Diarrheal diseases represent a major health burden in developing countries.
      Parenteral immunization typically does not induce efficient protection against
      enteropathogens because it does not stimulate migration of immune cells to the
      gut. Retinoic acid (RA) is critical for gut immunity, inducing upregulation of
      gut-homing receptors on activated T cells. In this study, we have demonstrated
      that RA can redirect immune responses elicited by s.c. vaccination of mice from
      skin-draining inguinal LNs (ingLNs) to the gut. When present during priming, RA
      induced robust upregulation of gut-homing receptors in ingLNs, imprinting gut
      homing capacity on T cells. Concurrently, RA triggered the generation of gut
      tropic IgA+ plasma cells in ingLNs and raised the levels of antigen-specific IgA
      in the intestinal lumen and blood. RA applied s.c. in vivo induced autonomous RA
      production in ingLN DCs, further driving efficient induction of gut-homing
      molecules on effector cells. Importantly, RA-supplemented s.c. immunization
      elicited a potent immune response in the small intestine that protected mice from
      cholera toxin-induced diarrhea and diminished bacterial loads in Peyer patches
      after oral infection with Salmonella. Thus, the use of RA as a gut-homing
      navigator represents a powerful tool to induce protective immunity in the
      intestine after s.c. immunization, offering what we believe to be a novel
      approach for vaccination against enteropathogens.

PMID- 21737879
TI  - VIP blockade leads to microcephaly in mice  via disruption of Mcph1-Chk1
      signaling.
AB  - Autosomal recessive primary microcephaly (MCPH) is a genetic disorder that causes
      a reduction of cortical outgrowth without severe interference with cortical
      patterning. It is associated with mutations in a number of genes encoding protein
      involved in mitotic spindle formation and centrosomal activities or cell cycle
      control. We have shown previously that blocking vasoactive intestinal peptide
      (VIP) during gestation in mice by using a VIP antagonist (VA) results in
      microcephaly. Here, we have shown that the cortical abnormalities caused by
      prenatal VA administration mimic the phenotype described in MCPH patients and
      that VIP blockade during neurogenesis specifically disrupts Mcph1 signaling. VA
      administration reduced neuroepithelial progenitor proliferation by increasing
      cell cycle length and promoting cell cycle exit and premature neuronal
      differentiation. Quantitative RT-PCR and Western blot showed that VA
      downregulated Mcph1. Inhibition of Mcph1 expression led to downregulation of Chk1
      and reduction of Chk1 kinase activity. The inhibition of Mcph1 and Chk1 affected
      the expression of a specific subset of cell cycle-controlling genes and turned
      off neural stem cell proliferation in neurospheres. Furthermore, in vitro
      silencing of either Mcph1 or Chk1 in neurospheres mimicked VA-induced inhibition
      of cell proliferation. These results demonstrate that VIP blockade induces
      microcephaly through Mcph1 signaling and suggest that VIP/Mcph1/Chk1 signaling is
      key for normal cortical development.

PMID- 21737880
TI  - Prevention of murine autoimmune diabetes  by CCL22-mediated Treg recruitment  to
      the pancreatic islets.
AB  - Type 1 diabetes is characterized by destruction of insulin-producing beta cells
      in the pancreatic islets by effector T cells. Tregs, defined by the markers CD4
      and FoxP3, regulate immune responses by suppressing effector T cells and are
      recruited to sites of action by the chemokine CCL22. Here, we demonstrate that
      production of CCL22 in islets after intrapancreatic duct injection of double
      stranded adeno-associated virus encoding CCL22 recruits endogenous Tregs to the
      islets and confers long-term protection from autoimmune diabetes in NOD mice. In
      addition, adenoviral expression of CCL22 in syngeneic islet transplants in
      diabetic NOD recipients prevented beta cell destruction by autoreactive T cells
      and thereby delayed recurrence of diabetes. CCL22 expression increased the
      frequency of Tregs, produced higher levels of TGF-beta in the CD4+ T cell
      population near islets, and decreased the frequency of circulating autoreactive
      CD8+ T cells and CD8+ IFN-gamma-producing T cells. The protective effect of CCL22
      was abrogated by depletion of Tregs with a CD25-specific antibody. Our results
      indicate that islet expression of CCL22 recruits Tregs and attenuates autoimmune
      destruction of beta cells. CCL22-mediated recruitment of Tregs to islets may be a
      novel therapeutic strategy for type 1 diabetes.

PMID- 21737881
TI  - Helicobacter pylori infection prevents allergic  asthma in mouse models through 
      the induction of regulatory T cells.
AB  - Atopic asthma is a chronic disease of the airways that has taken on epidemic
      proportions in the industrialized world. The increase in asthma rates has been
      linked epidemiologically to the rapid disappearance of Helicobacter pylori, a
      bacterial pathogen that persistently colonizes the human stomach, from Western
      societies. In this study, we have utilized mouse models of allergic airway
      disease induced by ovalbumin or house dust mite allergen to experimentally
      examine a possible inverse correlation between H. pylori and asthma. H. pylori
      infection efficiently protected mice from airway hyperresponsiveness, tissue
      inflammation, and goblet cell metaplasia, which are hallmarks of asthma, and
      prevented allergen-induced pulmonary and bronchoalveolar infiltration with
      eosinophils, Th2 cells, and Th17 cells. Protection against asthma was most robust
      in mice infected neonatally and was abrogated by antibiotic eradication of H.
      pylori. Asthma protection was further associated with impaired maturation of lung
      infiltrating dendritic cells and the accumulation of highly suppressive Tregs in
      the lungs. Systemic Treg depletion abolished asthma protection; conversely, the
      adoptive transfer of purified Treg populations was sufficient to transfer
      protection from infected donor mice to uninfected recipients. Our results thus
      provide experimental evidence for a beneficial effect of H. pylori colonization
      on the development of allergen-induced asthma.

PMID- 21737882
TI  - Mice lacking microRNA 133a  develop dynamin 2-dependent  centronuclear myopathy.
AB  - MicroRNAs modulate cellular phenotypes by inhibiting expression of mRNA targets.
      In this study, we have shown that the muscle-specific microRNAs miR-133a-1 and
      miR-133a-2 are essential for multiple facets of skeletal muscle function and
      homeostasis in mice. Mice with genetic deletions of miR-133a-1 and miR-133a-2
      developed adult-onset centronuclear myopathy in type II (fast-twitch) myofibers,
      accompanied by impaired mitochondrial function, fast-to-slow myofiber conversion,
      and disarray of muscle triads (sites of excitation- contraction coupling). These
      abnormalities mimicked human centronuclear myopathies and could be ascribed, at
      least in part, to dysregulation of the miR-133a target mRNA that encodes dynamin
      2, a GTPase implicated in human centronuclear myopathy. Our findings reveal an
      essential role for miR-133a in the maintenance of adult skeletal muscle
      structure, function, bioenergetics, and myofiber identity; they also identify a
      potential modulator of centronuclear myopathies.

PMID- 21737883
TI  - Identification of an IFN-gamma/mast cell axis  in a mouse model of chronic
      asthma.
AB  - Asthma is considered a Th2 cell-associated disorder. Despite this, both the Th1
      cell-associated cytokine IFN-gamma and airway neutrophilia have been implicated
      in severe asthma. To investigate the relative contributions of different immune
      system components to the pathogenesis of asthma, we previously developed a model
      that exhibits several features of severe asthma in humans, including airway
      neutrophilia and increased lung IFN-gamma. In the present studies, we tested the
      hypothesis that IFN-gamma regulates mast cell function in our model of chronic
      asthma. Engraftment of mast cell-deficient KitW(-sh/W-sh) mice, which develop
      markedly attenuated features of disease, with wild-type mast cells restored
      disease pathology in this model of chronic asthma. However, disease pathology was
      not fully restored by engraftment with either IFN-gamma receptor 1-null (Ifngr1-/
      ) or Fcepsilon receptor 1gamma-null (Fcer1g-/-) mast cells. Additional analysis,
      including gene array studies, showed that mast cell expression of IFN-gammaR
      contributed to the development of many FcepsilonRIgamma-dependent and some
      FcepsilonRIgamma-independent features of disease in our model, including airway
      hyperresponsiveness, neutrophilic and eosinophilic inflammation, airway
      remodeling, and lung expression of several cytokines, chemokines, and markers of
      an alternatively activated macrophage response. These findings identify a
      previously unsuspected IFN-gamma/mast cell axis in the pathology of chronic
      allergic inflammation of the airways in mice.

PMID- 21737884
TI  - What is the evidence for our standards of care?
AB  - The term evidence-based medicine is overused, abused, and is beginning to ring
      hollow. It is not that evidence (or at least of what most people in biomedicine
      think evidence-based medicine should strive to be) is a bad thing. Rather, there
      is more rhetoric about evidence than there is actual evidence to support the
      degree of talk.

PMID- 21737886
TI  - Pancreatic neoplasm in 2011: an update.
AB  - Pancreatic cancer still is a significant, unresolved therapeutic challenge with
      nearly similar incidence and mortality rates. It is the most lethal type of
      digestive cancer with a 5-year survival rate of 5%. Adjuvant chemotherapy remains
      to be gemcitabine alone or combined with infusional 5-fluorouracil with radiation
      therapy. Nevertheless, only a few patients survive for at least 5 years after R0
      resection and adjuvant therapy. Most patients need palliative treatment. Once
      pancreatic cancer becomes metastatic, it is uniformly fatal with an overall
      survival of typically 6 months from diagnosis. Chemotherapy is an important
      component of palliative care but must be administered as a part of a
      multidisciplinary approach, including palliation of pain, managing weight loss,
      and deterioration in functional status. Gemcitabine has been the standard in both
      locally advanced and metastatic disease. The addition of the tyrosine kinase
      inhibitor erlotinib prolongs median survival for only 2 weeks. While gemcitabine
      based regimens are currently accepted as the standard first-line treatment of
      patients with locally advanced or metastatic pancreatic adenocarcinoma, there is
      no consensus regarding treatment in the second-line setting. It will not be
      untrue to say that there are no real medical breakthroughs with regards to
      improving the prognosis of pancreatic cancer as of 2011. On the other hand, we
      have made some progress in patients with advanced pancreatic neuroendocrine
      tumors. These patients have a 5-year survival that can range from 97% in benign
      insulinomas to as low as 30% in non-functional metastatic pancreatic
      neuroendocrine tumors. Treatment options may include surgery, transarterial
      chemoembolization of liver metastases, and cytotoxic therapy such as
      streptozotocin, 5-fluorouracil or doxorubicin. Somatostatin analogues, like
      octreotide, have been proven to prolong progression-free survival in patients
      with metastatic neuroendocrine tumors of midgut origin. In 2011, two targeted
      agents, a tyrosine kinase inhibitor sunitinib and mTOR inhibitor everolimus have
      been approved by FDA for pancreatic neuroendocrine tumors. With these approvals,
      U.S. physicians can now offer their patients with progressive pancreatic
      neuroendocrine tumors. Patients with any stage of pancreatic cancer should be
      considered candidates for clinical trials.

PMID- 21737887
TI  - Screening and detection of pancreatic cancer. Highlights from the "2011 ASCO
      Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Screening and early detection of pancreatic cancer has the potential to
      substantially impact outcomes in this deadly disease. Over the last ten years
      several cohort studies have been conducted and report on the yield of screening
      in high risk populations. With better understanding of the cellular compartments
      and the genetic and epigenetic changes that occur, biomarkers have also emerged
      as promising means of early detection. In this paper we summarize the results of
      the latest screening cohort and highlight a novel proteomic approach that may be
      used in future biomarker studies.

PMID- 21737885
TI  - Osteoimmunology at the nexus of arthritis, osteoporosis, cancer, and infection.
AB  - Over the past decade and a half, the biomedical community has uncovered a
      previously unappreciated reciprocal relationship between cells of the immune and
      skeletal systems. Work in this field, which has been termed "osteoimmunology,"
      has resulted in the development of clinical therapeutics for seemingly disparate
      diseases linked by the common themes of inflammation and bone remodeling. Here,
      the important concepts and discoveries in osteoimmunology are discussed in the
      context of the diseases bridging these two organ systems, including arthritis,
      osteoporosis, cancer, and infection, and the targeted treatments used by
      clinicians to combat them.

PMID- 21737888
TI  - Biomarkers and pharmacogenetics in pancreatic cancer. Highlights from the "2011
      ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Appropriate identification and validation of biomarkers as well as
      pharmacogenetics are important in formulating patient-oriented, individualized
      chemotherapy or biological therapy in cancer patients. These markers can be
      especially valuable in pancreatic cancer, where high mortality and complex
      disease biology are frequently encountered. Recently, several advances have been
      made to further our knowledge in this specific area of pancreatic cancer. In the
      2011 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers
      have presented several interesting results in biomarkers development: the
      identifications of 9 single nucleotide polymorphisms (SNPs) that is associated
      with positive efficacy of gemcitabine (Abstract #4022); the introduction of
      circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma
      (Abstract #e14657); the re-affirmation of plasma cytidine deaminase (CDA) as a
      positive predictive markers for gemcitabine efficacy, as well as the postulations
      that CDA*3 as a potential genotype marker to predict gemcitabine responses
      (Abstract #e14645); and finally the retrospective tumor tissues analysis in the
      Arbeitsgemeinschaft Internistische Onkologie (AIO) trial in an attempt for
      epidermal growth factor receptor (EGFR) pathway biomarker identifications
      (Abstract #4047).

PMID- 21737889
TI  - Diabetes and pancreatic cancer. Highlights from the "2011 ASCO Annual Meeting".
      Chicago, IL, USA; June 3-7, 2011.
AB  - Pancreatic cancer is the fourth leading cause of cancer death in the United
      States. Risk factors for pancreatic cancer are smoking, family history, chronic
      pancreatitis, and diabetes. There is controversy with regards to the causal
      relationship between diabetes and pancreatic cancer because many patients with
      pancreatic cancer have new onset diabetes. Abstracts presented at the 2011
      American Society of Clinical Oncology (ASCO) Annual Meeting highlighted and
      supported the positive association between pancreatic cancer and diabetes.
      Abstract #4102 reports a two-fold risk of pancreatic cancer in diabetic patients.
      Abstract #4063 also presented at the 2011 ASCO Meeting shows that metformin
      prolongs survival and decreases risk of death in patients with pancreatic
      malignancy and diabetes.

PMID- 21737890
TI  - Novel agents for the treatment of pancreatic adenocarcinoma. Highlights from the
      "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - There are urgent needs to develop novel and more effective regimens to improve
      outcomes of pancreatic cancer given its dismal prognosis and limited treatment
      options. Several phase I clinical trials involving novel agents were recently
      presented at the 2011 American Society of Clinical Oncology (ASCO) Annual
      Meeting. It appears that hedgehog inhibition with IPI-926 was well-tolerated and
      might be effective in treating pancreatic cancer when combined with gemcitabine.
      The survival benefits will be tested in the following randomized phase II trial.
      The new combination of gemcitabine and blockade of checkpoint kinases with
      AZD7762 showed an acceptable safety profile. Furthermore, inhibition of PI3K by
      BAY80-6946 was well tolerated with PET-CT suggesting reduction in FDG uptake in
      some pancreatic cancer. The benefits of above novel agents/regimens need to be
      further tested in phase II trials.

PMID- 21737891
TI  - Updates on first-line treatment of metastatic pancreatic adenocarcinoma.
      Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Despite the extensive research, mounting knowledge in the cancer field and
      enormous investments, pancreatic cancer remains a rather incurable disease with
      aggressive natural course and high mortality rate. The very slow progress is a
      result of the complex pathogenesis of this disease, which prevents us from
      targeting the culprit and making a step forward. Therefore, the field is still
      unexplored and this is a real challenge and opportunity for new ideas and novel
      approaches. In this paper, we will present the most interesting studies in the
      first line pancreatic cancer setting, presented at the American Society of
      Clinical Oncology (ASCO) 2011 Annual Meeting. While there are few studies testing
      the role of combining the cytotoxic S-1 and gemcitabine, the majority of the
      studies are examining the safety and impact of adding to the classic gemcitabine
      treatment novel molecular agents which target key pathways or overexpressed
      proteins.

PMID- 21737892
TI  - Adjuvant Therapy of Pancreatic Cancer. Highlights from the "2011 ASCO Annual
      Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Strong evidence exists for the use of adjuvant chemotherapy following surgical
      resection in pancreatic cancer, whereas the role of adjuvant chemoradiotherapy
      remains controversial. The optimal time to initiate adjuvant therapy has yet to
      be elucidated, but is usually started 2-10 weeks following resection. First line
      adjuvant chemotherapy is gemcitabine, as this drug has demonstrated the better
      efficacy in studies. Other chemotherapeutic agents and gemcitabine in combination
      with biologic agents are under investigation. Furthermore, predicting response to
      gemcitabine based chemotherapy and other adjuvant therapies will be invaluable in
      guiding the practitioner to choose the most appropriate adjuvant treatment. Once
      adjuvant therapy has been started, accurately quantifying response to therapy is
      also important. The adjuvant regimen may be appropriately modified if response is
      inadequate. This review is an update from the 2011 American Society of Clinical
      Oncology (ASCO) Annual Meeting regarding recent developments in the adjuvant
      treatment of pancreatic cancer with regards to choice of adjuvant regimen, timing
      of adjuvant therapy, predicting response to therapy and measuring response to
      adjuvant therapy. We will present the findings from Abstracts #4039, #4042,
      #e14519, #4118, and #4024. In conclusion, multiple adjuvant therapeutic regimens
      are associated with incremental improvements in the management of pancreatic
      cancer. The timing of initiation of adjuvant therapy appears to be important in
      outcomes. Research is ongoing into markers that can predict response to adjuvant
      therapy.

PMID- 21737893
TI  - Locally advanced pancreatic adenocarcinoma: are we making progress?. Highlights
      from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Pancreatic cancer, as the 4th leading cause of cancer death in the U.S., remains
      a challenging disease for all oncologists. Less than 20% of all cases could be
      potentially cured by surgical resection, while the majority of cases are deemed
      either unresectable or metastatic upon diagnosis. In this year's American Society
      of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with
      novel approaches towards treating locally advanced pancreatic cancer. The LAP-07
      study, a large phase III study with two separate randomizations, updated their
      accrual status, but with no interim data yet reported (Abstract #e14619). A
      single institutional review study reported its promising results on the
      incorporation of interferon to chemoradiation, but the toxicities could be
      concerning (Abstract #e14648). Abstract #e14607 demonstrated promising survival
      data from a tri-modality approach incorporating local and systemic chemotherapy
      concurrent with external beam radiation as well as radiofrequency ablation. The
      tolerability of sorafenib in locally advanced pancreatic cancer was shown in a
      small phase I study (Abstract #e14525). CyberKnife(r) stereotactic body radiation
      therapy was investigated as a modality for local palliation (Abstract #e14506).
      More effective therapeutic agents and approaches are still needed in this
      difficult disease. This highlight article will focus on the management of locally
      advanced pancreatic cancer.

PMID- 21737894
TI  - Updates on treatment of gemcitabine-refractory pancreatic adenocarcinoma.
      Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Gemcitabine monotherapy and gemcitabine-based regimens are the current standard
      of care for locally advanced or metastatic pancreatic adenocarcinoma. However,
      there is still great controversy over the role of salvage chemotherapy after
      failure of gemcitabine. This review is an update on the 2011 American Society of
      Clinical Oncology (ASCO) Annual Meeting regarding the most important developments
      in the treatment of refractory pancreatic cancer, as they were reported in
      Abstracts #e14542 and #e14588.

PMID- 21737895
TI  - Palliative care of pancreatic cancer. Highlights from the "2011 ASCO Annual
      Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Pancreatic cancer is one of the most fatal malignancies. Palliative care
      represents an important aspect of management in patients with pancreatic
      malignancy. Identifying and treating disease related symptoms are very important.
      As a physician taking care of these patients it is essential to know these
      symptoms and treatment modalities. Common problems include biliary obstruction,
      anticoagulation, and pain management. This review discusses the data presented at
      the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting symptom
      management and supportive care strategies including Abstracts #e14665, #e14622,
      and #LBA9014. Success is needed in managing these symptoms to palliate patients
      with advanced pancreatic cancer. It is important for oncologists to recognize the
      importance of supportive measures that can minimize the symptoms of advanced
      disease and side effects of cancer treatment.

PMID- 21737896
TI  - Novel agents in the treatment of unresectable neuroendocrine tumors. Highlights
      from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Pancreatic neuroendocrine tumors represent a small percentage of all pancreatic
      tumors (1.3%) but their incidence is rising. Prior to 2011, the only approved
      agent for unresectable disease was streptozicin (often used in combination with
      doxorubicin) but the efficacy of this drug is in question and there had not been
      any new drugs approved for this disease in more than 20 years. Recently there has
      been new excitement for the treatment of advanced neuroendocrine tumors including
      those of the pancreas (pNET) with FDA approval of 2 new agents in 2011. One of
      these agents was everolimus, an mTOR inhibitor, which was approved on the basis
      of a landmark phase III study (RADIANT-3). At the 2011 American Society of
      Clinical Oncology (ASCO) Annual Meeting, several abstracts were presented
      reviewing novel agents in the treatment of advanced NET. Three abstracts looked
      at characteristics of patients treated on the RADIANT-3 study and looked at the
      role of prior chemotherapy use (Abstract #4103), somatostatin analog use
      (Abstract #4010), and updated safety data (Abstract #4009) from this trial.
      Additionally, an abstract was presented (Abstract 4008) looking at updated data
      from the other targeted agent approved for advanced pNET, sunitinib, a multi
      tyrosine kinase inhibitor, which demonstrated improvement in progression-free
      survival compared to placebo. Novel agents were also presented, including a phase
      II trial looking at the combination of sorafenib and bevacizumab (Abstract
      #4113), and a phase I trial looking at a novel somatostatin analog, pasireotide,
      in combination with everolimus (Abstract #4120) The authors review and summarize
      these abstracts in this article.

PMID- 21737897
TI  - Adjuvant treatment for ampullary cancer. Highlights from the "2011 ASCO Annual
      Meeting". Chicago, IL, USA; June 3-7, 2011.
AB  - Ampullary cancer is an uncommon tumor and tends to have a better prognosis than
      pancreatic cancer. However, one half of patients will die from recurrent disease
      suggesting the need for effective adjuvant therapy. Currently, there is lack of
      randomized trials to guide the use of adjuvant therapy in ampullary cancer. At
      the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, the largest
      trial (Abstract #4006) evaluating adjuvant treatment of ampullary cancer was
      presented.

PMID- 21737898
TI  - Evaluation of the quality of life after surgical treatment of chronic
      pancreatitis.
AB  - OBJECTIVE: Pain is the main symptom of chronic pancreatitis. However, in addition
      to an improvement in pain symptoms, an increase in the quality of life also
      influences therapeutic success. The present paper evaluates the influence of
      surgery on chronic pancreatitis, and the early and late postoperative quality of
      life. PATIENTS: From March 2000 until April 2005, 51 patients underwent surgical
      treatment for chronic pancreatitis at our institution. INTERVENTION: Thirty-nine
      (76.5%) patients were operated on according to the Frey procedure and, in 12
      (23.5%) patients, a Whipple procedure was performed. STUDY DESIGN: Patient data
      were documented throughout the duration of the hospital stay. Postoperative
      follow-up data were recorded retrospectively. MAIN OUTCOME MEASURES:
      Postoperative follow-up with postoperative pain scores and quality of life were
      carried out using a standardized questionnaire. RESULTS: During a median follow
      up period of 50 months, an improvement in pain scores was observed in 92.3% of
      the patients in the Frey group and in 66.7% in the Whipple group. The indices for
      global quality of life and for physical and emotional status increased in both
      surgical groups. CONCLUSION: For patients with chronic pancreatitis, the decisive
      factor is the quality of life, particularly concerning pain and metabolic
      changes. The Frey procedure seems to offer advantages with respect to long-term
      freedom of pain and low risk of surgery-induced pancreatic insufficiency.

PMID- 21737899
TI  - Using the 4-hour Post-ERCP amylase level to predict post-ERCP pancreatitis.
AB  - CONTEXT: Post-ERCP pancreatitis is the most common complication of endoscopic
      retrograde cholangiopancreatography (ERCP). A simple method of predicting
      patients who are at risk of developing post-ERCP pancreatitis is needed to allow
      those at low risk to be discharged on the same day of their procedure. The aim of
      this study was to confirm that 4-hour post-ERCP serum amylase level is predictive
      of post-ERCP pancreatitis. PATIENTS: A study of 886 ERCPs performed at a single
      centre was conducted. MAIN OUTCOME MEASURE: Four-hour amylase level was recorded,
      along with patient demographics, procedural details, presence of pancreatogram,
      and morbidity and mortality. RESULTS: Pancreatitis occurred in 4.4% of ERCPs.
      Hyperamylasaemia was found to be predictive of post-ERCP pancreatitis, with other
      risk factors being a younger age and pancreatogram. Hyperamylasaemia was also
      predictive of post-ERCP pancreatitis in the subgroup of patients who had
      undergone pancreatogram. CONCLUSIONS: The 4-hour amylase level is a useful
      measure in the prediction of post-ERCP pancreatitis. Patients who have undergone
      pancreatogram should be admitted if 4-hour amylase level is greater than 2.5
      times the upper limit of reference. Patients who have not undergone pancreatogram
      should be admitted if 4-hour amylase level is greater than 5 times the upper
      limit of reference.

PMID- 21737900
TI  - Inoperable pancreatic cancer patients who have prolonged survival exhibit an
      increased risk of cholangitis.
AB  - CONTEXT: Endoscopically placed metal stents, which are patent for 4-9 months,
      have been the favored decompressive strategy for biliary obstruction due to
      inoperable pancreatic cancer in order to minimize interventions. However, in the
      past decade chemotherapeutic options have improved survival. This raises the
      question of whether metal stents will continue to be the optimal method of
      decompression. OBJECTIVE: We performed a study to determine the outcome of
      patients with non-operatively managed pancreatic adenocarcinoma with regards to
      the development of cholangitis. DESIGN: We reviewed all ERCP performed for
      malignant distal biliary obstruction in between December 1999 and December 2005
      at University of California, San Francisco (UCSF). PATIENTS: Only patients who
      received chemotherapy for pancreatic adenocarcinoma were included. Patients who
      underwent surgical biliary diversion procedures were excluded. PRIMARY OUTCOME
      MEASUREMENT: The primary outcome was the development of cholangitis requiring
      hospitalization. RESULTS: Among 200 patients with malignant distal biliary
      obstruction who underwent endoscopic biliary decompression procedures, 54 met
      study criterion. Metal stents were employed in 90.7% of these cases. The median
      survival of this population was 12.7 months (range: 2.6-34.6 months). Only 3 of
      26 patients (11.5%) surviving one year or less developed cholangitis compared to
      13 of 28 (46.5%) who survived more than one year. Thus patients surviving greater
      than one year had a five fold increase in the odds of developing cholangitis
      (odds ratio: 4.92; P=0.017). CONCLUSIONS: This cohort of inoperable pancreatic
      cancer patients undergoing chemotherapy survived longer than the expected patent
      period of metal stents employed for biliary decompression. The occurrence of
      cholangitis requiring hospitalization does increase markedly among long term
      survivors.

PMID- 21737901
TI  - CT attenuation of unilocular pancreatic cystic lesions to differentiate
      pseudocysts from mucin-containing cysts.
AB  - CONTEXT: There is extensive overlap among the imaging characteristics of
      pseudocyst, mucinous cystic neoplasm (MCN) and side branch intraductal papillary
      mucinous neoplasm (IPMN) on CT images. OBJECTIVE: The purpose of this study was
      to evaluate the usefulness of attenuation measurement in differentiating
      pseudocysts from MCN and IPMN of pancreas on CT images. PATIENTS: Seventy-five
      pathologically proven unilocular pancreatic cysts including 31 pseudocysts, 29
      MCN and 15 IPMN imaged with multidetector computed tomography (MDCT) before
      resection were evaluated. MAIN OUTCOME MEASURES: Attenuation values were measured
      by conventional region of interest (ROI) method. DESIGN: Attenuation values (in
      Hounsfield unit, HU) were compared between the cyst pathologies. Receiver
      operating characteristic (ROC) curve analysis was performed to obtain the best
      attenuation threshold between mucin-containing cysts and pseudocysts. Correlation
      between attenuation values and cyst size was assessed. RESULTS: Maximum
      transaxial diameters of pseudocysts (4.5 cm), MCNs (3.7 cm) and IPMNs (4.0 cm)
      were comparable (P=0.919). Mean attenuation was 18.9 HU, 13.0 HU and 11.4 HU for
      pseudocyst, MCNs and IPMNs, respectively. Attenuations were significantly higher
      in pseudocysts versus mucin-containing (MCN+IPMN) cysts (P=0.001) and comparable
      between MCNs and IPMNs (P=0.390). ROC curve showed 14.5 HU the best cut-off
      (accuracy: 73.5%) for differentiating pseudocysts from mucin-containing cysts
      (P<0.001). Pancreatic cyst attenuation measurement did not significantly
      correlate with cyst size (r=-0.03, P=0.772). CONCLUSION: Attenuation measurement
      may help in differentiating pseudocysts from unilocular mucin-containing simple
      cysts of the pancreas on CT images.

PMID- 21737903
TI  - The pattern of neural elements in the islets of normal and diseased pancreas and
      in isolated islets.
AB  - CONTEXT: The association between islet cells and neural elements, the so-called
      "neuro-insular complex", has been known for centuries. OBJECTIVE: We examined the
      expression of beta-III tubulin, in normal pancreases from organ donors, surgical
      specimens of chronic pancreatitis, surgical specimens of ductal type carcinoma,
      isolated and purified islets of a 57-year-old male and the pancreases of adult
      Syrian golden hamsters by immunohistochemistry using a monoclonal antibody to
      beta-tubulin. RESULTS: In the normal pancreas of humans and hamsters, beta-III
      tubulin was expressed in alpha- and beta-cells, but not in PP cells, neural
      fibers and gangliae. Occasionally, intra-and peri-insular neural elements were
      also found. In chronic pancreatitis and pancreatic cancer samples, the number of
      beta-cells and the immunoreactivity of the beta-III tubulin antibody in islet
      cells were decreased in most cases. In cultured human islets, devoid of neural
      elements, no correlation was found between the expression of beta-III tubulin and
      islet cell hormones. CONCLUSION: Beta-III tubulin is only expressed in the islets
      derived from the dorsal pancreas and in neural elements. In chronic pancreatitis
      and pancreatic cancer swelling of intra- and peri-insular nerves occurs, possibly
      in response to the loss of beta-cells. The secretion of insulin and the
      expression of beta-tubulin seem to be regulated by nerves.

PMID- 21737902
TI  - Substance P and calcitonin gene related peptide mediate pain in chronic
      pancreatitis and their expression is driven by nerve growth factor.
AB  - CONTEXT: Calcitonin gene-related peptide (CGRP), substance P and nerve growth
      factor play an important role in inflammatory pain in various somatic pain models
      but their role in chronic pancreatitis has not been well studied. OBJECTIVES: The
      aim of this study was to investigate the effects of intrathecal administration of
      calcitonin gene-related peptide antagonist and substance P receptor antagonist on
      pain behavior in a rat model of chronic pancreatitis and to determine whether
      nerve growth factor drives the up-regulation of expression of these neuropeptides
      in sensory neurons. METHODS: Pancreatitis was induced by retrograde infusion of
      trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks
      post infusion continuous intrathecal infusion of the calcitonin gene-related
      peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or
      its inactive enantiomer CP-96344 was administered for seven days. The effects of
      treatment on pancreatic hyperalgesia were assessed by sensitivity of the
      abdominal wall to von Frey filament probing as well as by the nocifensive
      response to electrical stimulation of the pancreas. In a separate experiment
      chronic pancreatitis was induced and pancreas specific dorsal root ganglion
      neurons labeled with DiI were assessed for calcitonin gene-related peptide and
      substance P immunoreactivity. RESULTS: Intrathecal infusion of calcitonin gene
      related peptide and neurokinin-1 receptor antagonists significantly attenuated
      behavioral pain responses in rats with chronic pancreatitis. Further, treatment
      of chronic pancreatitis rats with nerve growth factor antibody significantly
      reduced pancreas specific neurons expressing calcitonin gene-related peptide and
      substance P in thoracic dorsal root ganglion. CONCLUSIONS: Calcitonin gene
      related peptide and substance P mediate pancreatic hyperalgesia in chronic
      pancreatitis and nerve growth factor in turn sustains the up-regulation of these
      neuropeptides in pancreatic sensory neurons.

PMID- 21737904
TI  - Acute pancreatitis in the course of meprobamate poisoning.
AB  - CONTEXT: We report a case of massive poisoning with meprobamate leading to acute
      pancreatitis. CASE REPORT: A 43-year-old patient with a history of schizophrenia
      and multiple suicide attempts was admitted to the intensive care unit for severe
      poisoning with meprobamate (voluntary ingestion of 60 g). On admission, the
      patient was deeply comatose with low blood pressure and hypothermia. Laboratory
      analysis revealed leukocytosis and high lipase and amylase serum levels. There
      was no eosinophilia. Abdominal computed tomography showed pancreatitis grade A.
      The patient was intubated and ventilated, and intravenous dopamine was infused.
      The patient regained consciousness and was extubated five days later. Improvement
      in pancreatic tests was noted several days later. The outcome was favorable.
      DISCUSSION: According to the Naranjo probability scale, meprobamate-induced acute
      pancreatitis was probable. Acute pancreatitis in meprobamate poisoning is
      exceptional. The pathogenesis of pancreatitis-induced meprobamate poisoning may
      be explained by two mechanisms: stimulation of pancreatic secretion secondary to
      cholinergic activation and pancreatic ductal hypertension. CONCLUSIONS: The signs
      of severe meprobamate toxicity are numerous including cardiovascular and central
      nervous symptoms. Acute pancreatitis should also be added as a possible
      manifestation of meprobamate poisoning.

PMID- 21737905
TI  - Autoimmune neutropenia associated with autoimmune pancreatitis.
AB  - CONTEXT: We report a rare case of autoimmune neutropenia associated with
      autoimmune pancreatitis. CASE REPORT: A 61-year-old man was referred to our
      hospital with slight epigastralgia. He had been admitted to another hospital with
      exacerbation of diabetes and jaundice. Blood tests showed low white blood cell
      and neutrophil counts (1,800 uL-1 and 3%, respectively), and elevated
      transaminase, biliary enzyme, amylase and lipase levels. Serum IgG and IgG4
      levels were elevated to 2,693 mg/dL and 454 mg/dL, respectively. Abdominal CT
      showed diffuse pancreatic swelling, and MRCP revealed diffuse narrowing of the
      main pancreatic duct and dilation of the common bile duct. An additional EUS-FNA
      was performed in our hospital. Laboratory data, imaging and histopathological
      findings confirmed the diagnosis of autoimmune pancreatitis. However, the low
      white blood cell count continued. For additional investigation, a bone marrow
      examination was performed, indicating a granulocyte maturation disorder.
      Moreover, anti-neutrophil antibodies were positive. Therefore, a diagnosis of
      autoimmune neutropenia associated with autoimmune pancreatitis was made. After
      steroid therapy, the anti-neutrophil antibodies disappeared and the white blood
      cell count was within the reference limit. No recurrence of disease has been
      observed since then. CONCLUSION: Autoimmune neutropenia, which is positive for
      anti-neutrophil antibodies, can be associated with autoimmune pancreatitis.

PMID- 21737906
TI  - Delayed pancreatic fistula after pancreaticoduodenectomy. A case report.
AB  - CONTEXT: Pancreatic fistulas still occur despite refinements in both surgical
      technique and perioperative management after a pancreaticoduodenectomy. However,
      the occurrence of delayed pancreatic fistulas is very rare. CASE REPORT: A 62
      year-old woman diagnosed with a lower biliary carcinoma had undergone a pylorus
      preserving pancreaticoduodenectomy. The postoperative course was uneventful and
      the patient was discharged from the hospital after 16 days. One year after
      surgery, she was admitted to our hospital with a fluid collection around the
      pancreaticojejunal anastomosis. A catheter was inserted percutaneously and the
      fluid collection was drained. The amylase value of the discharge was
      significantly elevated (119,500 IU/L). One week later, a fistulography showed no
      significant collection and the tube was clamped. The patient was discharged from
      the hospital without symptoms. CONCLUSIONS: It is important to consider the
      occurrence of a delayed pancreatic fistula if the patient suffers from any
      symptoms. It is then necessary to proceed rapidly.

PMID- 21737907
TI  - Giant Brunner's gland adenoma of the duodenal bulb presenting with ampullary and
      duodenal obstruction mimicking pancreatic malignancy.
AB  - CONTEXT: Brunner's gland adenoma is a rare benign duodenal neoplasm. It usually
      presents with luminal obstruction or gastrointestinal bleeding. In rare cases, it
      may mimic a pancreatic malignancy and may present with obstructive jaundice. CASE
      REPORT: A 65-year-old female presented with a two-month history of abdominal
      pain, early satiety and retrosternal burning pain. Liver function tests showed
      elevated enzymes with normal bilirubin. Imaging studies revealed a large mass in
      relation to the uncinate process of the pancreas and the distal duodenum along
      with the dilated common bile duct and the main pancreatic duct. Initial
      endoscopic evaluation failed to make a correct diagnosis. Repeat endoscopic
      evaluation combined with endoscopic sonography, however, revealed a large
      polypoid mass arising from the duodenal bulb. The patient underwent a
      transduodenal polypectomy. A diagnosis of Brunner's gland adenoma was made on
      histopathological examination. CONCLUSION: Giant Brunner's adenoma may have
      unusual presentations. It may present with the features of ampullary obstruction
      mimicking periampullary or pancreatic malignancies. Extensive preoperative
      evaluation is required to reach a correct diagnosis in order to avoid more
      extensive surgery.

PMID- 21737908
TI  - Foregut cystic malformations in the pancreas. Are definitions clearly
      established?
AB  - CONTEXT: Foregut cystic malformations are common lesions in the mediastinum but
      are rarely found in subdiaphragmatic locations. Only a few cases have been
      described within the pancreas where they can easily be misdiagnosed as cystic
      neoplasms. CASE REPORT: We herein present the case of a 37-year-old female with
      acute cholangitis in whom a diagnostic work-up revealed a 1 cm solid-cystic
      heterogeneous lesion located at the head of the pancreas. The patient underwent a
      pancreaticoduodenectomy. Pathological evaluation demonstrated a cystic cavity
      lined by pseudostratified tall columnar ciliated epithelium with goblet cells,
      but lacking cartilage or smooth muscle bundles. Thus, the final diagnosis of the
      lesion was a ciliated foregut cyst of the pancreas. CONCLUSIONS: A review of the
      cases published regarding these lesions shows great variability in the taxonomy
      and a lack of accuracy in the definitions of each different subtype. An easy to
      use algorithm for the diagnosis of foregut cystic malformations subtypes, based
      on epithelial lining and wall features, is presented.

PMID- 21737909
TI  - Rheumatoid arthritis associated with the use of Sandostatin(r) LAR(r) depot in a
      patient with pancreatic neuroendocrine tumor. An association or a coincidence?
      The first case report.
AB  - CONTEXT: Sandostatin(r) LAR(r) depot is a synthetic analogue of the naturally
      occurring hormone somatostatin and is indicated for certain patients with
      acromegaly and severe diarrhea and flushing episodes associated with metastatic
      carcinoid tumors and for the long-term treatment of the profuse watery diarrhea
      associated with VIP-secreting tumors in patients in whom initial treatment with
      immediate release Sandostatin(r) injection has been shown to be effective and
      tolerated. The most common toxicities include biliary disorders, gastrointestinal
      disorders, injection-site pain, hypoglycemia and hyperglycemia. Rheumatoid
      arthritis or similar toxicities have not been associated with Sandostatin(r)
      LAR(r) depot. CASE REPORT: We present a 53-year-old female with a history of
      neuroendocrine tumor of the pancreas with metastasis to the liver, lung developed
      joint pains in the hands as well as feet accompanied with intermittent swelling
      in the morning and pain in the bilateral joints in the hands as well as feet
      following 45th cycle of Sandostatin(r) LAR(r) depot at a dose of 30 mg. All the
      work-up including rheumatoid factor, anti nuclear antibody, cryoglobulins were
      within normal limits except her erythrocyte sedimentation rate was elevated. No
      radiological abnormalities were revealed. Her symptoms improved after we reduced
      the dose to 20 mg. DISCUSSION: Her Naranjo scale was 7, suggesting a probable
      relation. The patient had four signs and symptoms as required by the American
      College of Rheumatology for the diagnosis of rheumatoid arthritis. The
      association of the rheumatoid arthritis with Sandostatin(r) LAR(r) depot may be a
      rare complication but with the extended use beyond acromegaly and carcinoid to
      acute esophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal, and
      pancreatic external fistulae, short bowel syndrome, a dumping syndrome and
      acquired immunodeficiency syndrome-related refractory hypersecretory diarrhea,
      physicians should be made aware of this probable toxicity. Further research is
      warranted to understand this association.

PMID- 21737910
TI  - The "hanging maneuver" technique during pancreaticoduodenectomy: The result of a
      technical evolution to approach the superior mesenteric artery.

PMID- 21737911
TI  - When pathology marries clinics: the Honolulu consensus document and the
      guidelines of the International Association of Pancreatology on Autoimmune
      Pancreatitis.

PMID- 21737912
TI  - The ethylene signal mediates induction of GmATG8i in soybean plants under
      starvation stress.
AB  - In higher plants, autophagy-related genes (ATGs) appear to play important roles
      in development, senescence, and starvation responses. Hormone signals underlying
      starvation-induced gene expression are involved in the expression of ATGs. An
      effect of starvation stress on the expression of ATGs and ethylene-related genes
      in young seedlings of soybean (Glycine max [L.] Merr. cv. Fukuyutaka) was
      analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) showed that
      the expression levels of GmATG8i and GmATG4 increase in a starvation medium, but
      at a null or marginal level in a sucrose/nitrate-rich medium. The expression of
      GmACC synthase and GmERF are also upregulated in the starvation medium. In
      addition, immunoblot revealed that ethylene insensitive 3 (Ein3), an ethylene
      induced transcription factor are accumulated in seedlings subjected to severe
      starvation stress. These results indicate that starvation stress stimulates the
      expression of GmATG8i and ethylene signal-related genes. Since the ethylene
      signal is involved in senescence and various environmental stresses, it is
      possible that starvation stress-induced autophagy is partly mediated by the
      ethylene signaling.

PMID- 21737913
TI  - Prevention of oxidative DNA degradation by copper-binding peptides.
AB  - Free divalent ions of copper (Cu) are capable of generating radical species such
      as hydroxyl radicals in the presence of hydrogen peroxide or ascorbic acid
      through Harbor-Weiss-like reactions under physiological conditions. It has been
      reported that radical-mediated damage to DNA molecules in animal cells leads to
      programmed cell death. Hence it is important to seek for methods to prevent Cu
      mediated DNA damage. In this study we identified on effect of Cu binding of short
      peptides (chiefly Gly-Gly-His tripeptide) in the prevention of DNA degradation
      caused by Cu-mediated reactions in the presence of hydrogen peroxide and of
      ascorbic acid.

PMID- 21737914
TI  - Sublethal doses of surfactants induce premature senescence in normal human skin
      cells.
AB  - We evaluated the cytotoxicity of surfactants in human cells. Synthetic
      surfactants showed different cytotoxicity levels depending on their structures.
      The cytotoxicity of commercial washing products was determined mainly by the
      contents of surfactants. All of them induced premature senescence in normal
      cells, but not in tumor-derived or immortalized cells, under sublethal
      conditions. Residual surfactants might be a risk factor for skin aging.

PMID- 21737915
TI  - Targeted overexpression of Drosophila transglutaminase-B induced characteristic
      phenotypes in a manner similar to transglutaminase-a.
AB  - The Drosophila transglutaminase gene (CG7356) encodes two transglutaminases, dTG
      A and dTG-B. To understand the roles of dTG-B during the development of the fly,
      we examined phenotypes induced through ectopic expression of dTG-B.
      Overexpression of dTG-B induced rough eye and extra wing crossvein phenotypes.
      These phenotypes were similar to those observed in the case of targeted
      overexpression of dTG-A.

PMID- 21737916
TI  - Improvement of a Venus-based bimolecular fluorescence complementation assay to
      visualize bFos-bJun interaction in living cells.
AB  - Bimolecular fluorescence complementation (BiFC) assay makes it possible to
      visualize protein-protein interactions in living cells. In this assay, Venus, a
      bright-yellow variant of green fluorescent protein, is known to produce
      fluorescent backgrounds due to non-specific interactions. In this study we found
      that the V150A mutation increased by 8.6-fold the signal-to-noise ratio in the
      BiFC assay of bFos-bJun interaction.

PMID- 21737917
TI  - A simple, large-scale overexpression method of deriving carbon monoxide
      dehydrogenase II from thermophilic bacterium Carboxydothermus hydrogenoformans.
AB  - We established an Na(2)S-free, large-scale overexpression system of deriving CODH
      II from thermophilic bacterium Carboxydothermus hydrogenoformans in Escherichia
      coli using a large-scale fermentor. Recombinant-CODH II showed a CO oxidation
      activity of 9,600 U/mg. In addition, recombinant-CODH II exhibited considerable
      CO(2) reduction activity, of 16.9 U/mg.

PMID- 21737918
TI  - A convenient purification method for pyridylamino monosaccharides.
AB  - Pyridylamino derivatization is suitable for the microanalysis of sugars, but
      there is a problem in that by-products of the labeling reaction and fluorescent
      substances from samples occasionally interfere with the detection of pyridylamino
      sugars. Especially, interference by them is serious in monosaccharide analysis. I
      have developed a convenient purification method for pyridylamino monosaccharides
      by the use of a spin column with boronate-conjugated resin.

PMID- 21737919
TI  - Neuroprotective Kaurane Diterpenes from Fritillaria ebeiensis.
AB  - The new kaurane diterpene, ent-3beta-butanoyloxykaur-15-en-17-ol, and four known
      kaurane diterpenes were isolated from the bulbs of Fritillaria ebeiensis. Their
      structures were elucidated on the basis of extensive spectroscopic analyses (IR,
      ESI-MS, HR-ESI-MS, 1-D and 2-D NMR). All the isolates showed neuroprotective
      effects against MPP(+)-induced neuronal cell death in human dopaminergic
      neuroblastoma SH-SY5Y cells.

PMID- 21737920
TI  - Stereochemical differentiation in the Simmons-Smith reaction for cyclopropanated
      glucopyranose derivatives as molecular probes for glycosidases.
AB  - Glucopyranose analogues carrying a bicyclo[4.1.0]heptane framework and the
      diastereomer of the cyclopropane moiety were synthesized as the unit for
      molecular probes to mimic the unstable transition state conformation of the
      glucopyranose ring in enzymatic hydrolysis. The synthesis features
      differentiation of the alpha- and beta-stereoselectivity in cyclopropanation of
      the corresponding cyclohexene derivative.

PMID- 21737921
TI  - Photostability of lycopene dispersed in an aqueous solution.
AB  - Lycopene dispersed in aqueous solutions with different dissolved oxygen contents
      was photo-irradiated by using a xenon weather meter, and the contents of lycopene
      and dissolved oxygen were measured. Both the degradation of lycopene and the
      consumption of dissolved oxygen followed a first-order kinetics model. There was
      a proportional relationship between the degradation content of lycopene and the
      consumption of dissolved oxygen. These results indicate that dissolved oxygen
      would also be involved in the photolysis of lycopene.

PMID- 21737922
TI  - Fish oil feeding up-regulates the expression of 5-aminolevulinate synthase 2 mRNA
      in rat brain.
AB  - In this study, we investigated the effect of fish oil on gene expression in the
      cerebral cortex, and found that 5-aminolevulinate synthase 2 (ALAS2) mRNA
      expression was up-regulated by fish oil feeding. ALAS2 promoter activity was
      found to be regulated by retinoic acid. Our results suggest that fish oil
      modulates neuronal functions via heme synthesis.

PMID- 21737923
TI  - Greater effectiveness of epsilon-viniferin in red wine than its monomer
      resveratrol for inhibiting vascular smooth muscle cell proliferation and
      migration.
AB  - Resveratrol is a strong candidate for explaining an irreversible correlation
      between red wine consumption and coronary heart disease. The present study
      examined the effect of epsilon-viniferin, a dehydrodimer of resveratrol, on
      vascular smooth muscle cells (VSMCs), because epsilon-viniferin functions are
      poorly understood in spite of its comparable content to resveratrol in red wines
      and grapes. Both epsilon-viniferin and resveratrol inhibited platelet-derived
      growth factor-induced cell proliferation, migration, and reactive oxygen species
      (ROS) production, in addition to inducing nitric oxide generation. epsilon
      Viniferin was more effective than resveratrol in these effects, except for
      inhibiting ROS production. The compounds also increased the expression of the
      antioxidant enzyme, hemeoxygenase-1, via transcription factor Nrf2. The
      phosphatidylinositol 3-kinase-Akt pathway was implicated in resveratrol-dependent
      nuclear Nrf2 accumulation, whereas extracellular signal-regulated kinase and p38
      were involved in epsilon-viniferin-induced Nrf2 accumulation. These data suggest
      that epsilon-viniferin may function more effectively than resveratrol in
      different mechanisms and cooperatively with resveratrol in preventing
      atherosclerosis.

PMID- 21737924
TI  - Effects of mutations of Lys41 and Asp102 of bacteriorhodopsin.
AB  - Bacteriorhodopsin (BR) is a retinal protein that functions as a light-driven
      proton pump. In this study, six novel mutants including K41E and D102K, were
      obtained to verify or rule out the possibility that residues Lys41 and Asp102 are
      determinants of the time order of proton release and uptake, because we found
      that the order was reversed in another retinal protein archaerhodopsin 4 (AR4),
      which had different 41th and 102th residues. Our results rule out that
      possibility and confirm that the pK(a) of the proton release complex (PRC)
      determines the time order. Nevertheless, mutations, especially D102K, were found
      to affect the kinetics of proton uptake substantially and the pK(a) of Asp96.
      Compared to the wild-type BR (BR-WT), the decay of the M intermediate and proton
      uptake in the photocycle was slowed about 3-fold in D102K. Hence those residues
      might be involved in proton uptake and delivery to the internal proton donor.

PMID- 21737925
TI  - Production and characterization of a glycolipid biosurfactant, mannosylerythritol
      lipid B, from sugarcane juice by Ustilago scitaminea NBRC 32730.
AB  - Mannosylerythritol lipids (MELs) are glycolipid biosurfactants excreted by fungal
      strains. They show not only excellent surface-active properties but also
      versatile biochemical actions. Ustilago scitaminea NBRC 32730 has been reported
      mainly to produce a mono-acetylated and di-acylated MEL, MEL-B, from sucrose as
      sole carbon source. In order to make biosurfactant production more efficient, we
      focused our attention on the use of sugarcane juice, one of the most economical
      resources. The fungal strain produced MEL-B at the yield of 12.7 g/L from only
      sugarcane juice containing 22.4% w/w sugars. Supplementation with organic (yeast
      extract, peptone, and urea) and inorganic (sodium nitrate and ammonium nitrate)
      nitrogen sources markedly enhanced the production yield. Of the nitrogen sources,
      urea gave the best yield. Under optimum conditions, the strain produced 25.1 g/L
      of MEL-B from the juice (19.3% sugars) supplemented with 1 g/L of urea in a jar
      fermenter at 25  degrees C over 7 d. The critical micelle concentration (CMC) and
      the surface-tension at the CMC for the present MEL-B were 3.7*10(-6) M and 25.2
      mN/m respectively. On water-penetration scan, the biosurfactant efficiently
      formed the lamella phase (L(alpha)) and myelins over a wide range of
      concentrations, indicating excellent surface-active and self-assembling
      properties. More significantly, the biosurfactant showed a ceramide-like skin
      care property in a three-dimensional cultured human skin model. Thus, sugarcane
      juice is likely to be effective in glycolipid production by U. scitaminea NBRC
      32730, and should facilitate the application of MELs.

PMID- 21737926
TI  - Salt-tolerant and thermostable glutaminases of cryptococcus species form a new
      glutaminase family.
AB  - Genes encoding salt-tolerant and thermostable glutaminases were isolated from
      Cryptococcus species. The glutaminase gene, CngahA, from C. nodaensis NISL-3771
      was 2,052 bp in length and encoded a 684-amino acid protein. The gene, CagahA,
      from C. albidus ATCC20293 was 2,100 bp in length and encoded a 700-amino acid
      protein. These glutaminases showed 44% identity. By searches on public databases,
      we found that these glutaminases are not similar to any other characterized
      glutaminases, but are similar to certain hypothetical proteins. On searching the
      conserved domain with the basic local alignment search tool (BLAST), it was found
      that they have the amidase domain and are members of the amidase signature
      superfamily. They were expressed in Saccharomyces cerevisiae, and their activity
      was detected on the cell surface. This study revealed that they are a new type of
      glutaminase with the amidase signature sequence, and that they form a new
      glutaminase family.

PMID- 21737927
TI  - Growth inhibition and chromosomal instability of cultured marsupial (opossum)
      cells after treatment with DNA polymerase alpha inhibitor.
AB  - The DNA replication mechanism has been well established for eutherian mammals
      (placental mammals such as humans, mice, and cattle), but not, to date, for
      metatherian mammals (marsupials such as kangaroos, koalas, and opossums). In this
      study, we found that dehydroaltenusin, a selective inhibitor of mammalian
      (eutherian) DNA polymerase alpha, clearly suppressed the growth of metatherian
      (opossum and rat kangaroo) cultured cells. In cultured opossum (OK) cells,
      dehydroaltenusin also suppressed the progression of DNA replication. These
      results suggest that dehydroaltenusin inhibits metatherian as well as eutherian
      DNA replication. Dehydroaltenusin treatment of OK cells engendered fluctuations
      in the numbers of chromosomes in the OK cells as well as inhibition of cell
      growth and DNA replication. This suggests that partial inhibition of DNA
      replication by dehydroaltenusin causes chromosomal instability in cultured cells.

PMID- 21737928
TI  - Amelioration of D-galactosamine-induced acute liver injury in rats by dietary
      supplementation with betaine derived from sugar beet molasses.
AB  - The effects of betaine supplementation on D-galactosamine-induced liver injury
      were examined in terms of hepatic and serum enzyme activities and of the levels
      of glutathione and betaine-derived intermediates. The rats induced with liver
      injury showed marked increases in serum enzyme activity, but those receiving
      dietary supplementation of 1% betaine showed enzyme activity levels similar to a
      control group without liver injury. Administration of betaine also increased both
      hepatic and serum glutathione levels, even following D-galactosamine injection.
      The activity of glutathione-related enzymes was markedly decreased following
      injection of D-galactosamine, but remained comparable to that of the control
      group in rats receiving 1% betaine. The concentrations of hepatic S-adenosyl
      methionine and cysteine showed similar trends to that observed for hepatic
      glutathione levels. These results indicate that 1% betaine has a hepatoprotective
      effect by increasing hepatic and serum glutathione levels along with glutathione
      related enzyme activities in rats.

PMID- 21737929
TI  - Structure-activity relationship of anthelmintic cyclooctadepsipeptides.
AB  - The relationship between cyclooctadepsipeptides and their anthelmintic efficacy
      was examined by converting the natural products, PF1022A, PF1022E and PF1022H.
      Some analogues substituted at the para position of the phenyllactate moiety
      showed higher or equivalent activity against the parasitic nematode, Ascaridia
      galli in chicken when compared with the parent compounds. It is suggested that
      lipophilicity and the polar surface area, in addition to structural requirements
      of the derivatives, influenced the anthelmintic efficacy in vivo.

PMID- 21737930
TI  - Identification of aromatic residues critical to the DNA binding and ligand
      response of the Bacillus subtilis QdoR (YxaF) repressor antagonized by
      flavonoids.
AB  - Bacillus subtilis LmrA and QdoR (formerly YxaF) are paralogous transcriptional
      regulators that repress their regulon comprising the lmrAB operon, the qdoR gene,
      and the qdoI-yxaH operon, by binding to the LmrA/QdoR boxes located in the
      promoter regions. Detachment of them followed by derepression of the target genes
      is induced by certain flavonoids. To identify the residues critical to the ligand
      response in QdoR, we selected eight residues based on structural information,
      produced eight single-mutated QdoRs in which each residue was replaced with
      alanine, and evaluated their capacities for DNA binding and the flavonoid
      response by gel retardation analysis. The three mutants, carrying the alanine
      substitution at Phe87, Trp131, or Phe135, showed features distinctly different
      from those of the wild type and from each other. We further examined the in vivo
      function of the mutant with alanine substitution at Trp131 by reporter assay.
      This largely supported the corresponding in vitro results. The in vitro and in
      vivo data suggest that Phe87, Trp131, and Phe135, forming a hydrophobic cluster
      in QdoR, play crucial roles in the DNA binding, flavonoid accommodation, and/or
      conformational change triggered by ligand binding.

PMID- 21737931
TI  - Expression of recombinant human interferon-gamma with antiviral activity in the
      bi-cistronic baculovirus-insect/larval system.
AB  - A bi-cistronic baculovirus-insect/larval system containing a polyhedron promoter,
      an internal ribosome entry site (IRES), and an egfp gene was developed as a cost
      effective platform for the production of recombinant human interferon gamma
      (rhIFN-gamma). There was no significant difference between the amounts of rhIFN
      gamma produced in the baculovirus-infected Spodoptera frugiferda 21 cells grown
      in serum-free medium and the serum-supplemented medium, while the Trichoplusia ni
      (T. ni) and Spodoptera exigua (S. exigua) larvae afforded rhIFN-gamma amounting
      to 1.08+/-0.04 and 9.74+/-0.35 ug/mg protein respectively. The presence of non
      glycosylated and glycosylated rhIFN-gamma was confirmed by immunoblot and lectin
      blot. The immunological activity of purified rhIFN-gamma, with 96% purity by
      Nickel (II)-nitrilotriacetic acid (Ni-NTA) affinity chromatography, was similar
      to that commercially available. Moreover, the rhIFN-gamma protein from T. ni had
      more potent antiviral activity. These findings suggest that this IRES-based
      expression system is a simple and inexpensive alternative for large-scale protein
      production in anti-viral research.

PMID- 21737932
TI  - Homocysteine-induced caspase-3 activation by endoplasmic reticulum stress in
      endothelial progenitor cells from patients with coronary heart disease and
      healthy donors.
AB  - Previous studies have suggested an association of hyperhomocysteinemia-induced
      vascular pathology with enhanced apoptotic potential of endothelial progenitor
      cells in patients with coronary heart disease. Our results indicate that 500
      umol/L homocysteine induced endothelial progenitor cell apoptosis and activation
      of caspase-3, both of which were abolished by 100 umol/L and 200 umol/L
      salubrinal, an agent that prevents endoplasmic reticulum stress-induced
      apoptosis. The addition of 500 umol/L homocysteine caused a release of Ca(2+)
      from intracellular stores, and enhanced phosphor-eukaryotic initiation factor
      2alpha phosphorylation at Ser51 and the expression of a glucose-regulated protein
      of 78 kDa and a C/EBP homologous protein independently of extracellular Ca(2+).
      These effects of homocysteine on endothelial progenitor cells were significantly
      greater in patients with coronary heart disease than in healthy donors. These
      findings suggest that homocysteine induces endoplasmic reticulum stress-mediated
      activation of caspase-3 in endothelial progenitor cells, an event that is
      enhanced in patients with coronary heart disease. Furthermore, enhanced
      endoplasmic reticulum stress-mediated activation of caspase-3 in endothelial
      progenitor cells might be involved in hyperhomocysteinemia-associated vascular
      pathology.

PMID- 21737933
TI  - Mechanism of the lifespan extension of Caenorhabditis elegans by electrolyzed
      reduced water--participation of Pt nanoparticles.
AB  - Electrolyzed reduced water (ERW) contains a large amount of molecular hydrogen
      and a small amount of Pt nanoparticles (Pt NPs). We have found that ERW
      significantly extended the lifespan of Caenorhabditis elegans in a novel culture
      medium designated Water Medium. In this study, we found that synthetic Pt NPs at
      ppb levels significantly extended the nematode lifespan and scavenged reactive
      oxygen species (ROS) in the nematode induced by paraquat treatment. In contrast,
      a high concentration of dissolved molecular hydrogen had no significant effect on
      the lifespan of the nematode. These findings suggest that the Pt NPs in ERW,
      rather than the molecular hydrogen, extend the longevity of the nematode, at
      least partly by scavenging ROS.

PMID- 21737934
TI  - Isoegomaketone induces apoptosis through caspase-dependent and caspase
      independent pathways in human DLD1 cells.
AB  - Isoegomaketone (IK) is an essential oil component of Perilla frutescens (L.), but
      the mechanism by which IK induces apoptosis has never been studied. The purpose
      of this study was to elucidate the IK-induced apoptotic pathway in DLD1 human
      colon cancer cells. We observed that IK treatment over 24 h significantly
      inhibited cell viability in a dose-dependent manner. We also found that IK
      triggered cleavage of PARP. Moreover, IK treatment resulted in cleavage of
      caspase-8, -9, and -3 in a dose- and time-dependent manner. IK treatment also
      resulted in cleavage of Bid and translocation of Bax, and triggered the release
      of cytochrome c from the mitochondria to the cytoplasm. Furthermore, it resulted
      in the translocation of apoptosis inducing factor (AIF), a caspase-independent
      mitochondrial apoptosis factor, from the mitochondria into the nucleus. Overall,
      these results suggest that IK induces apoptosis through caspase-dependent and
      capase-independent pathways in DLD1 cells.

PMID- 21737935
TI  - Predicting the buckwheat flour ratio for commercial dried buckwheat noodles based
      on the fluorescence fingerprint.
AB  - A rapid method for predicting the buckwheat flour ratio of dried buckwheat
      noodles was developed by using the fluorescence fingerprint and partial least
      squares regression. Fitting the calibration model to validation datasets showed
      R(2)=0.78 and SEP=12.4%. The model was refined for a better fit by deleting
      several samples containing additional ingredients. The best fit was finally
      obtained (R(2)=0.84 and SEP=10.4%) by deleting the samples containing vinegar,
      green tea, seaweed, polysaccharide thickener, and yam. This result demonstrates
      that a calibration model with high accuracy could be constructed based on samples
      similar in material composition. The developed methodology requires no complex
      preprocessing, enables rapid measurement with a small sample amount, and would
      thus be suitable for practical application to the food industry.

PMID- 21737936
TI  - Molecular cloning and characterization of a linalool synthase from lemon myrtle.
AB  - Using a homology-based PCR strategy, we identified a cDNA with sequence
      similarity to linalool synthase from lemon myrtle. Functional expression of the
      cDNA (designated BcLS) gene in Escherichia coli yielded an active enzyme capable
      of catalyzing the conversion of geranyl diphosphate to (-)-linalool, i.e., an
      acyclic monoterpene alcohol, and to lesser amounts of cyclic monoterpenes. The
      kinetic parameters of BcLS were similar to those of synthases producing cyclic
      monoterpenes. PCR analysis revealed that the BcLS gene transcript was
      ubiquitously expressed in lemon myrtle and was upregulated in response to
      jasmonic acid treatment. Although the physiological role of neryl diphosphate
      (NPP) dependency of BcLS remains unclear, the cyclization activity of BcLS was
      enhanced when NPP was used as substrate, resulting in predominant production of
      cyclic monoterpenes. These findings indicate that BcLS has novel specificity and
      kinetic parameters, but its physiological responses to stresses such as insect
      damage appear to be similar to known linalool synthases.

PMID- 21737937
TI  - Enrichment and characterization of a trichloroethene-dechlorinating consortium
      containing multiple "dehalococcoides" strains.
AB  - A microbial consortium that reductively dechlorinates trichloroethene, cis-1,2
      dichloroethene (cis-DCE), and vinyl chloride (VC) to ethene with methanogenesis
      was enriched from chloroethene-contaminated soil from Japan. Dechlorination
      activity was maintained for over 4 years. Using quantitative polymerase chain
      reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) analysis
      targeting the "Dehalococcoides" 16S rRNA gene, four strains were detected. Their
      growth and dechlorination activities were classified into two types: one that
      grows by converting cis-DCE to ethene and the other that grows by converting cis
      DCE to VC. Then, the vcrA and bvcA genes encoding cis-DCE/VC reductive
      dehalogenases were detected. Inhibitors of methanogenesis (2
      bromoethanesulfonate) and sulfidogenesis (molybdate) led to accumulation of cis
      DCE and of VC respectively. These results suggest that methanogens and sulfate
      reducing bacteria can play a significant role in dechlorination by
      "Dehalococcoides."

PMID- 21737938
TI  - Interleukin-22 protects against acute alcohol-induced hepatotoxicity in mice.
AB  - The protective effects of interleukin-22 (IL-22) on acute alcohol-induced liver
      injury were investigated. Mice were gavaged with 7 doses of alcohol (56% wt/vol,
      15.2 mL/kg of body weight for each dose) over the 24 h, and IL-22 (0.5 mg/kg BW)
      was given to the mice by injection into the tail vein 1 h after alcohol
      administration. The results indicated that acute alcohol administration caused
      prominent hepatic microvesicular steatosis and an elevation of serum transaminase
      activities, induced a significant decrease in hepatic glutathione in conjunction
      with enhanced lipid peroxidation, and increased hepatocyte apoptosis as well as
      hepatic TNF-alpha production. IL-22 treatment attenuated these adverse changes
      induced by acute alcohol administration. The protective effects of IL-22 on
      alcohol-induced hepatotoxicity were due mainly to its anti-inflammatory, anti
      oxidant, and anti-apoptotic features.

PMID- 21737939
TI  - Isolation and identification of the umami enhancing compounds in Japanese soy
      sauce.
AB  - To clarify the key compounds that account for the umami taste of soy sauce, a
      typical Japanese soy sauce, Koikuchi Shoyu, was separated by preparative
      chromatography, and the umami enhancing fractions were screened on the basis of
      an umami intensity of a 6.0 mM monosodium L-glutamate (MSG) solution. Liquid
      chromatography-time of flight mass spectrometry (LC-TOFMS), 1D/2D nuclear
      magnetic resonance spectroscopy (NMR) studies of the umami enhancing fractions
      led to the identification of N-(1-deoxy-D-fructos-1-yl)pyroglutamic acid (Fru
      pGlu), N-(1-deoxy-D-fructos-1-yl)valine (Fru-Val), N-(1-deoxy-D-fructos-1
      yl)methionine (Fru-Met), pyroglutamylglutamine (pGlu-Gln), and
      pyroglutamylglycine (pGlu-Gly). Although all the compounds identified were at sub
      threshold concentrations in the soy sauce, a taste reconstitution experiment
      revealed that they contributed part of the umami taste of the soy sauce.

PMID- 21737940
TI  - Effects of chondroitin sulfate and its oligosaccharides on toll-like receptor
      mediated IL-6 secretion by macrophage-like J774.1 cells.
AB  - The effects of two types of chondroitin sulphate (CS), CS-A and CS-C, their
      oligosaccharides (oligo-CSs), and disaccharides (Di-CSs) on toll-like receptor
      (TLR)-mediated secretion of interleukin (IL)-6 were compared using macrophage
      like cell line J774.1. IL-6 secretion in the J774.1 cells was markedly increased
      by Pam3CS4, LPS, and CpG, the ligands to TLR1/2, 4, and 9 respectively. Among
      these three ligands, CpG-induced IL-6 was most clearly suppressed by CSs and
      their digests. Suppression of IL-6 secretion by smaller sized CS-A was stronger
      than that by intact CS-A, whereas no such size-dependent suppression was apparent
      for CS-C. Di-4S, the disaccharide unit of the CS-A digest, also showed much
      stronger suppression than Di-6S, the disaccharide unit of the CS-C digest, and
      the non-sulfated disaccharide unit, Di-0S. The suppressing activity of oligo-CSs,
      particularly Di-CSs, against TLR-mediated inflammation was dependent on the CS
      structure, including the sulfation site.

PMID- 21737941
TI  - Identification of 2,4-dihydroxy-2,5-dimethyl-3(2H)-thiophenone as a low-molecular
      weight yellow pigment in soy sauce.
AB  - The color of soy sauce is considered to be mainly attributable to melanoidins
      formed by the Maillard reaction. However, the chemical structure of melanoidins
      cannot be clarified, because melanoidins are high-molecular-weight heterogeneous
      polymers. We isolated a low-molecular-weight pigment from soy sauce and
      identified 2,4-dihydroxy-2,5-dimethyl-3(2H)-thiophenone as this pigment formed by
      the Maillard reaction, although its contribution to the total color of soy sauce
      was very low.

PMID- 21737942
TI  - Gastrointestinal digestion and absorption of Pen j 1, a major allergen from
      Kuruma prawn, Penaeus japonicus.
AB  - Tropomyosin had been identified as a major allergen in shrimp. The digestion and
      absorption of tropomyosin (Pen j 1) from kuruma prawn were investigated by ex
      vivo, in vitro, and in vivo techniques in order to elucidate the relationship
      between the allergenicity of the allergen and its gastrointestinal behavior. Pen
      j 1 transported the Caco-2 monolayer in a dose-dependent manner, and also
      enhanced the permeability of lucifer yellow, a marker of paracellular
      transportation, at high concentrations of the allergen. Studies with everted sacs
      revealed that Pen j 1 was rapidly degraded to small peptides (MW<3.5 kDa) and
      amino acids by intestinal proteases and absorbed from enterocytes. Furthermore,
      Pen j 1 orally administered to rats tended to remain in the stomach rather than
      in the small intestine, after which the allergen moved to the epithelial cells.
      These observations suggest that Pen j 1 may be absorbed via the gastric mucosa
      prior to its digestion in the intestines.

PMID- 21737943
TI  - Inhibition of premature death by isothiocyanates through immune restoration in LP
      BM5 leukemia retrovirus-infected C57BL/6 mice.
AB  - The purpose of this study was to determine the effect of isothiocyanates (ITCs)
      in delaying the progression of the murine immunodeficiency virus to murine AIDS,
      resulting in increased life span. Furthermore, we investigated the role of ITCs
      in modulating immune dysfunction caused by LP-BM5 retrovirus infection. Among the
      tested ITCs, oral administration of sulforaphane (SUL), benzyl isothiocyante
      (BITC), and phenethyl isothiocyanate (PEITC) showed the inhibition of premature
      death caused by LP-BM5 retrovirus infection, while indolo[3,2-b] carbazole (ICZ)
      and indole-3-carbinol (I3C) did not delay the progress of the LP-BM5 retrovirus
      to murine AIDS. Inhibition of premature death by BITC, PEITC, and SUL could be
      explained by restoration of the immune system and down regulation of free
      radicals. Dysfunction of T and B cell mitogenesis caused by retrovirus infection
      in primary cultured splenocytes has been partially recovered with administration
      of BITC, PEITC, and SUL. There was a shift from imbalanced cytokine production
      (increased Th2 and decreased Th1 cell cytokine production) into balanced Th1/Th2
      cell secretion of cytokines under administration of these ITCs during the
      development of murine AIDS. Hepatic vitamin E level was significantly restored by
      administration of these ITCs, in accordance with reduced hepatic lipid
      peroxidation levels. This study suggests that certain types of ITCs have
      beneficial effects in preventing premature death during progression to murine
      AIDS by restoration of immune dysfunction and removal of excessive free radicals,
      implying that selective usage of ITCs would be helpful in retarding the
      progression from HIV infection to AIDS.

PMID- 21737944
TI  - The biosynthesis of isoprenoids and the mechanisms regulating it in plants.
AB  - Plants synthesize isopentenyl diphosphate (IPP) via the mevalonate pathway and
      the methylerythritol phosphate (MEP) pathway. IPP is condensed to its allylic
      isomer, dimethylallyl diphosphate, to yield geranylgeranyl diphosphate, a common
      precursor for the production of cyclic diterpenoids. Studies of subcellular
      localization and of transgenic plants defective in the enzymes involved in the
      pathway have revealed that the synthesis processes of plastidic diterpenoids are
      metabolically separated in the plastids. Ditepenoid phytoalexins are synthesized
      through the plastidic MEP pathway in rice. The biosynthetic genes responsible for
      diterpenoid phytoalexins are clustered on the rice chromosomes, and the
      expression of them was coordinately regulated under stress conditions.
      Furthermore, a basic leucine zipper transcription factor, OsTGAP1, which is
      induced by the fungal chitin oligosaccharide elicitor, was identified as a key
      regulator of coordinated expression of the clustered biosynthetic genes for
      phytoalexin production in rice.

PMID- 21737945
TI  - Occurrence, biosynthesis, biodegradation, and industrial and medical applications
      of a naturally occurring epsilon-poly-L-lysine.
AB  - epsilon-Poly-L-lysine (epsilon-PL) consists of 25-35 L-lysine residues with
      linkages between the alpha-carboxyl groups and the epsilon-amino groups. It
      exhibits antimicrobial activity against a spectrum of microorganisms, including
      bacteria and fungi. Because of its high levels of safety and biodegradability, it
      is used as a food preservative in several countries. We recently identified an
      epsilon-PL synthetase (Pls) as a membrane protein, and investigated the catalytic
      mechanism. Pls was found to be an unusual non-ribosomal peptide synthetase (NRPS)
      like peptide synthetase producing epsilon-PL with chain-length diversity. In
      addition, transcriptional analysis of pls and a kinetic study of Pls further
      suggested that the Pls catalytic function is regulated by intracellular ATP, high
      levels of which are required for full enzymatic activity. Furthermore, it was
      found that acidic pH conditions during epsilon-PL fermentation are necessary for
      the accumulation of intracellular ATP, rather than inhibition of the epsilon-PL
      degrading enzyme.

PMID- 21737947
TI  - After the triumph of cardiovascular medicine over acute myocardial infarction at
      the end of the 20th Century. -Can we predict the onset of acute coronary
      syndrome? (Con)-.
AB  - Predicting acute cardiovascular ischemic events is a crucial and urgent issue in
      the current cardiovascular field. An enormous effort to develop methodologies to
      achieve this purpose is being undertaken in cardiovascular institutes worldwide.
      However, currently, there is no established method of determining acute
      cardiovascular ischemic events in advance. This article reviews the latest
      progress on understanding how these events occur and how they can be detected.
      This goal represents a great dream that has realistic expectations.

PMID- 21737948
TI  - Prediction of acute coronary syndrome by using multislice computed tomography. 
      Can we predict the onset of acute coronary syndrome? (Pro)-.
AB  - Predicting the occurrence of acute coronary syndrome (ACS) is a major clinical
      challenge for cardiologists. Multi-slice computed tomography (CT) has enabled
      easy detection and assessment of atherosclerotic coronary plaque, and therefore
      has considerable potential in the prevention of ACS. The recent development of 64
      slice cardiac CT enables detailed information on both plaque properties and
      characteristics to be obtained with excellent diagnostic accuracy. Cardiac CT
      therefore has great potential for detecting the unstable plaques that are prone
      to result in ACS.

PMID- 21737949
TI  - Beta-blocker therapy for patients with acute myocardial infarction. -Implications
      in the post-successful PCI Era in Japan-.

PMID- 21737950
TI  - Time in the therapeutic range during warfarin therapy in Japanese patients with
      non-valvular atrial fibrillation. - A multicenter study of its status and
      infuential factors-.
AB  - BACKGROUND: Time in the therapeutic range (TTR) assesses the appropriateness of
      international normalized ratio of prothrombin time (PT-INR) control during
      warfarin therapy. We examined the status of and the factors influencing TTR in
      Japanese patients with non-valvular atrial fibrillation (AF). METHODS AND
      RESULTS: We enrolled 501 AF patients (mean age, 70 +/- 10 years; males 66%; mean
      CHADS2 score 2.0 +/- 1.2) taking warfarin for >= 2 years from 5 prefectures. The
      PT-INR therapeutic range was set up according to the 2008 Japanese Guideline. TTR
      was 64 +/- 25% for all patients and varied from 56% to 74% with the institution.
      Time below and above TTR was 31 +/- 26% and 5 +/- 7%, respectively. TTR was not
      affected by gender or antiplatelet co-administration. TTR in patients < 70 and >=
      70 years old was 46 +/- 23% and 77 +/- 17%, respectively (P < 0.0001). TTR in
      patients with CHADS2 score <= 1 and >= 2 was 59 +/- 27% and 68 +/- 23%,
      respectively (P < 0.0001). TTR in patients with warfarin doses < 2.0, 2.0-4.9,
      and >= 5.0 mg/day was 72 +/- 22%, 63 +/- 25% and 48 +/- 24%, respectively (all P
      < 0.001). Multivariate analysis revealed age and warfarin dose as independent
      predictors of TTR. CONCLUSIONS: TTR is generally high in Japan, although it
      varies with institutions. Most of the time spent out of therapeutic range is
      below the range. TTR is influenced by age presumably because of the low range
      recommendation for elderly patients, and by warfarin dose presumably because of
      physicians' anxiety about the hemorrhage risk.

PMID- 21737951
TI  - Effect of atorvastatin vs. rosuvastatin on cardiac sympathetic nerve activity in
      non-diabetic patients with dilated cardiomyopathy.
AB  - BACKGROUND: Effects of statin therapy on cardiac sympathetic nerve activity in
      patients with chronic heart failure (CHF) have not previously been evaluated.
      METHODS AND RESULTS: To compare the effects of lipophilic atorvastatin and
      hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients
      with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were
      already receiving standard therapy for CHF, were randomized to atorvastatin (n =
      32) or rosuvastatin (n = 31). We evaluated cardiac sympathetic nerve activity by
      cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters
      and neurohumoral factors before and after 6 months of treatment. There were no
      differences in the baseline characteristics of the 2 groups. In the rosuvastatin
      group, there were no changes in MIBG parameters, left ventricular ejection
      fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT
      proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a
      significant increase in the delayed heart/mediastinum count ratio (2.18 +/- 0.4
      vs. 2.36 +/- 0.4, P < 0.0001), and the washout rate was significantly decreased
      (34.8 +/- 5.7 vs. 32.6 +/- 6.3%, P = 0.0001) after 6 months of treatment compared
      with the baseline values. The plasma NT-proBNP level was also significantly
      decreased (729 +/- 858 vs. 558 +/- 747 pg/ml, P = 0.0139). CONCLUSIONS:
      Lipophilic atorvastatin but not hydrophilic rosuvastatin improves cardiac
      sympathetic nerve activity in CHF patients with DCM.

PMID- 21737952
TI  - Genetic variation in gsalpha protein as a new indicator in screening test for
      vasovagal syncope.
AB  - BACKGROUND: A quantitative history using Calgary syncope syndrome score (CSSS) is
      able to define the likely cause of syncope, but there is still a lack of
      diagnostic screening tests for vasovagal syncope (VVS). The aim of the present
      study was to develop a screening test for VVS on the basis of CSSS and the
      relationship between polymorphic variants of the G-system signaling protein genes
      and tilting results. METHODS AND RESULTS: From 730 syncopal patients, 307
      consecutive subjects without structural and electrical abnormalities were
      genotyped and examined on blood pressure (BP) and tilt testing. Genotyping was
      performed using polymerase chain reaction-restriction fragment length
      polymorphism in genes encoding Gsalpha-protein GNAS1 (rs7121), G-protein beta 3
      subunit (rs5443) and the cardiac regulator of G-protein signaling RGS2 (rs4606).
      The control group consisted of 100 healthy volunteers with a negative history of
      syncope. From multivariate regression analysis, being a carrier of 393T GNAS1
      (odds ratio [OR], 2.29) and systolic BP (OR, 0.98) remained as independent
      factors associated with positive tilt results. The resultant screening test for
      VVS consisted of the following: carrier of 393T GNAS1; systolic BP < 131 mm Hg
      (from the receiver operating characteristic [ROC] curve); and CSSS >=-2. Using
      ROC curve analysis for systolic BP and CSSS, 2 final models for the screening
      test were constructed: highest sensitivity (89%) and highest specificity (99%).
      CONCLUSIONS: The novel screening test including the variation of Gsalpha protein
      gene seems to be helpful to identify tilt-induced vasovagal patients.

PMID- 21737953
TI  - A natural p300-specific histone acetyltransferase inhibitor, curcumin, in
      addition to angiotensin-converting enzyme inhibitor, exerts beneficial effects on
      left ventricular systolic function after myocardial infarction in rats.
AB  - BACKGROUND: A natural p300-specific histone acetyltransferase (HAT) inhibitor,
      curcumin, may have therapeutic potential for heart failure. However, it is
      unclear whether curcumin exhibits beneficial additive or synergistic effects on
      conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs).
      METHODS AND RESULTS: Rats were subjected to a sham operation or left coronary
      artery ligation. One week later, 34 rats with a moderate sized myocardial
      infarction (MI) were randomly assigned to 4 groups: solvents as control (n = 8),
      enalapril (an ACEI, 10 mg.kg-1.day-1) alone (n=8), curcumin (50 mg.kg-1.day-1)
      alone (n = 9) and enalapril plus curcumin (n = 9). Daily oral treatment was
      repeated and continued for 6 weeks. Echocardiographic data were similar among the
      4 groups before treatment. After treatment, left ventricular (LV) fractional
      shortening (FS) was significantly higher in the enalapril (29.0 +/- 1.9%) and
      curcumin (30.8 +/- 1.7%) groups than in the vehicle group (19.7 +/- 1.6%).
      Notably, LVFS further increased in the enalapril/curcumin combination group (34.4
      +/- 1.8%). Histologically, cardiomyocyte diameter in the non-infarct area was
      smaller in the enalapril/curcumin combination group than in the enalapril group.
      Perivascular fibrosis was significantly reduced in the enalapril/curcumin group
      compared with the curcumin group. CONCLUSIONS: A natural non-toxic dietary
      compound, curcumin, combined with an ACEI exerts beneficial effects on post-MI LV
      systolic function in rats.

PMID- 21737954
TI  - Hyponatremia and arginine vasopressin in early stage of ST-elevation acute
      myocardial infarction. -Surrogate markers or therapeutic targets?-.

PMID- 21737955
TI  - Ethnicity of patients with venous thromboembolism. -The incidence of venous
      thromboembolism in an Asian population-.

PMID- 21737956
TI  - Effects of quinidine on the action potential duration restitution property in the
      right ventricular outflow tract in patients with brugada syndrome.
AB  - BACKGROUND: On a cellular level, Brugada syndrome has been attributed to a deep
      phase 1 notch and subsequent shallow and prolonged repolarization in the right
      ventricular outflow tract (RVOT). A sodium channel mutation that leads to early
      inactivation of the late sodium current has been identified in some patients.
      Thus, drugs that inhibit the transient outward current (I(to)) responsible for
      the phase 1 notch and/or enhance the late sodium current might suppress
      arrhythmic events in patients with Brugada syndrome. The effects of quinidine
      gluconate, a potent inhibitor of I(to), on RVOT action potential duration (APD)
      restitution kinetics in patients with Brugada syndrome were evaluated. METHODS
      AND RESULTS: Programmed ventricular stimulation was performed in 9 Brugada
      syndrome patients by delivering up to 3 extrastimuli from the right ventricular
      apex and RVOT. RVOT monophasic action potentials (MAPs) were recorded before and
      after intravenous administration of quinidine (n=6) or ibutilide (n=3). All
      patients had inducible ventricular fibrillation (VF) before drug administration.
      Both quinidine and ibutilide increased steady-state and minimum RVOT MAP duration
      during programmed stimulation. Quinidine decreased the maximum slope of the RVOT
      APD restitution curve and VF could not be induced after administration of
      quinidine in 5 of the 6 patients. CONCLUSIONS: Quinidine appears to suppress the
      induction of VF by increasing RVOT MAP duration and decreasing the maximum slope
      of the restitution curve.

PMID- 21737957
TI  - Effect of adiponectin on cardiac allograft vasculopathy.
AB  - BACKGROUND: The role of adiponectin (APN), an adipose tissue-specific secretory
      protein, on chronic rejection after cardiac transplantation in APN-sense
      transgenic mice (APN-SE) was evaluated. METHODS AND RESULTS: Heterotopic cardiac
      transplantation in major histocompatibility complex class II-mismatched mice was
      performed. B6.C-H-2(bm12)KhEg (Bm12) hearts were transplanted into APN-SE, and
      allografts were harvested at 8 weeks after transplantation. Quantitative
      polymerase chain reaction (PCR) and immunohistochemical staining showed that the
      expression of both AdipoR1 and AdipoR2 was induced in APN-SE recipients.
      Neointimal hyperplasia was significantly decreased in allografts transplanted
      into APN-SE (luminal occlusion, 8.9 +/- 2.2%) compared to those transplanted into
      controls (49.4 +/- 10.5%; P=0.011). APN-SE showed significantly reduced mRNA
      levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-2, IL-6, and monocyte chemoattractant protein-1 (MCP-1) by quantitative PCR.
      Western blot analysis revealed that the protein levels of IFN-gamma and MCP-1
      were reduced in APN-SE recipients. Proliferation of smooth muscle cells
      stimulated with activated T cells was suppressed by APN addition, and this effect
      was canceled by treatment with an adenosine monophosphate-activated protein
      kinase (AMPK) inhibitor. CONCLUSIONS: APN plays a critical role in the
      attenuation of chronic rejection by suppressing inflammatory cytokine and
      chemokine expression and enhancing APN receptor expression. APN plays a
      beneficial role in reducing the progression of cardiac allograft vasculopathy
      through the AMPK pathway.

PMID- 21737958
TI  - Genome-wide investigation of the Rab binding activity of RUN domains: development
      of a novel tool that specifically traps GTP-Rab35.
AB  - The RUN domain is a less conserved protein motif that consists of approximately
      70 amino acids, and because RUN domains are often found in proteins involved in
      the regulation of Rab small GTPases, the RUN domain has been suggested to be
      involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site.
      However, since the Rab binding activity of most RUN domains has never been
      investigated, in this study we performed a genome-wide analysis of the Rab
      binding activity of the RUN domains of 19 different RUN domain-containing
      proteins by yeast two-hybrid assays with 60 different Rabs as bait. The results
      showed that only six of them interact with specific Rab isoforms with different
      Rab binding specificity, i.e., DENND5A/B with Rab6A/B, PLEKHM2 with Rab1A,
      RUFY2/3 with Rab33, and RUSC2 with Rab1/Rab35/Rab41. We also identified the
      minimal functional Rab35-binding site of RUSC2 (amino acid residues 982-1199) and
      succeeded in developing a novel GTP-Rab35-specific trapper, which we named RBD35
      (Rab-binding domain specific for Rab35). Recombinant RBD35 was found to trap GTP
      Rab35 specifically both in vitro and in PC12 cells, and overexpression of
      fluorescently tagged RBD35 in PC12 cells strongly inhibited nerve growth factor
      dependent neurite outgrowth.

PMID- 21737959
TI  - Pathologic features of polycystic thyroid disease: comparison with benign nodular
      goiter.
AB  - Polycystic thyroid disease (PCTD) is characterized by multiple thyroid cysts
      detected by ultrasonography, the absence of thyroid autoantibodies, and
      susceptibility to the development of hypothyroidism due to a high iodine intake. 
      It is necessary to obtain histopathological information on PCTD in order to
      clarify the cause of hypothyroidism.  We retrospectively reviewed three patients
      with PCTD and small papillary thyroid cancer who underwent thyroidectomy.  We
      observed the thyroid tissues pathologically in areas with and without multiple
      cysts, and compared them with those of multinodular goiter with cysts.  In the
      patients with PCTD, there were multiple enlarged follicles that resembled
      enlarged normal follicles and differed from those found in multinodular goiter in
      terms of their shape.  Huge follicles corresponded to the cysts that were
      detected by ultrasonography.  Each follicle contained colloid.  Follicular cells
      in enlarged follicles comprised low cuboidal epithelium that appeared normal. 
      These findings were common in the 3 patients with PCTD.  In Conclusion the PCTD
      patients had multiple enlarged follicles that seemed to decrease the total number
      of follicular cells, and may be a cause of hypothyroidism.  We believe that PCTD
      is a new entity of thyroid disease based on the pathological findings.

PMID- 21737960
TI  - The concept of metabolic syndrome: contribution of visceral fat accumulation and
      its molecular mechanism.
AB  - Although abdominal obesity or visceral obesity is considered to be one of the
      components of metabolic syndrome and to have an important role in a cluster of
      cardiovascular risks, there is no consensus about the definition and diagnostic
      criteria for this syndrome, probably because there is considerable disagreement
      about the location and definition of abdominal obesity or visceral obesity.In
      this review article, the important role of visceral fat accumulation in the
      development of a variety of lifestyle-related diseases is shown, including
      cardiovascular disease based on our clinical studies using CT scans, and the
      mechanism of these disorders is discussed, focusing on adipocytokines, especially
      adiponectin.The importance of diagnosing metabolic syndrome, in which visceral
      fat accumulation plays an essential role in the development of multiple risk
      factors, should be emphasized because lifestyle modification for the reduction of
      visceral fat may be very effective for the reduction of risks of this type,
      namely metabolic syndrome in the narrow sense.

PMID- 21737961
TI  - Serum paraoxonase 1 activity predicts arterial stiffness in renal transplant
      recipients.
AB  - AIM: Paraoxanase 1 (PON 1) has been shown to protect against atherosclerosis by
      modifying lipoproteins. Its activity decreases in dialysis patients but is
      restored after transplantation. Whether it affects arterial stiffness is unclear.
      In this study we aimed to investigate the effects of PON 1 on arterial stiffness
      in renal transplant patients. METHODS: Seventy renal transplant recipients were
      enrolled. Arterial stiffness was measured using a Syphmocor device. PON-1
      activity was assessed from the rate of enzymatic hydrolysis of paraoxon to p
      nitrophenol. RESULTS: Mean age was 39.0 +/- 9.6 years and 5.7% of the patients
      were diabetic. Post-transplant follow-up time was 46.7 +/- 37.9 months. Eighty
      five percent received anti-hypertensive and 12.9% anti-hyperlipidemic medication.
      Mean PON1 activity was 75.9 +/- 52.4 U/L. PON1 activity was negatively correlated
      with systolic and diastolic blood pressure, mean arterial pressure, LDL
      cholesterol and carotid-femoral pulse wave velocity (cf-PWV). Mean c-f PWV was
      8.10 +/- 1.39 m/s. Cf-PWV was positively correlated with age, systolic and
      diastolic blood pressure, mean arterial pressure, proteinuria and negatively
      correlated with PON1, PON1/HDL ratio and creatinine clearance. In linear
      regression analysis, PON1 was a predictor of cf-PWV in a model that included age,
      gender, diabetes, mean arterial pressure, urine protein level, creatinine
      clearance and PON 1. CONCLUSIONS: Reduced PON1 activity is significantly
      associated with increased arterial stiffness. The results of this study show the
      possible role of PON1 for arterial stiffening in renal transplant recipients.

PMID- 21737962
TI  - In vitro algaecide effect of disinfectants on Prototheca zopfii genotypes 1 and
      2.
AB  - Bovine mastitis due to Prototheca zopfii leads to reduced milk production and is
      difficult to cure. Therefore, prevention is the best approach and this is best
      achieved through the use of effective disinfectants. The aim of this study was to
      evaluate the in vitro algaecide efficacy of conventional disinfectants against
      strains of P. zopfii genotype 1 and 2. The minimal algaecide concentration (MAC)
      of alkyldiaminoethylglycine hydrochloride, chlorhexidine, dioxide chlorine,
      povidone iodine and sodium hypochlorous acid against 10 isolates and the type
      strain (SAG2063(T)) of P. zopfii genotype 1 as well as 10 isolates and the type
      strain (SAG2021(T)) of P. zopfii genotype 2 were examined using the micro
      dilution method. This in vitro study indicated that alkyldiaminoethylglycine
      hydrochloride, chlorhexidine, povidone iodine and sodium hypochlorous acid, but
      not dioxide chlorine, are effective against both genotypes of P. zopfii.

PMID- 21737963
TI  - First record of avian Plasmodium DNA from mosquitoes collected in the Yaeyama
      Archipelago, southwestern border of Japan.
AB  - We studied the prevalence of avian Plasmodium in 509 mosquitoes of 9 species
      collected from the Ishigaki and Iriomote islands in the Yaeyama Archipelago,
      located southwest from the mainland of Japan. Two identical avian Plasmodium
      lineages were detected from Culex (Culiciomyia) nigropunctatus. Detected lineages
      were phylogenetically classified into different clade to avian Plasmodium
      lineages from birds and mosquitoes in the mainland of Japan but identical to a
      lineage detected from a resident bird, White-breasted Waterken (Amaurornis
      phoenicurus). This is the first detection of avian Plasmodium DNA from mosquitoes
      in the Yaeyama Archipelago and suggested that resident birds might have been
      infected with an avian Plasmodium lineage specific to the studied area and C.
      nigropunctatus could be the candidate vector mosquito species.

PMID- 21737964
TI  - Rapid identification of hemoplasma species by palindromic nucleotide
      substitutions at the GAAA tetraloop helix in the specificity domain of
      ribonuclease P RNA.
AB  - We examined secondary structures of the ribonuclease P RNA sequences obtained
      from DNA databases, and identified a determinative prototype of the P12 helix
      peculiar to each species of hemoplasmas. This key structure will provide a rapid
      means for species identification of these uncultivable pathogens without making a
      phylogenetic tree based on alignments of nucleotide sequences. This procedure
      based on palindromic nucleotide substitutions at the stem portion of the P12
      helix provide clear information such as the level of heterogeneity within a
      species, the relatedness between species, or facilitating the characterization
      and clustering of specific strains. In conclusion, the PNS analysis is based on
      the evaluation of only the strategic and highly conserved genomic region in the
      specificity domain of RNase P RNA.

PMID- 21737965
TI  - A serological investigation of Bartonella henselae infection in cats in Turkey.
AB  - Bartonella henselae is the causative agent of cat scratch disease (CSD) in
      humans. Cats are the main reservoir of this bacterium and may infect humans
      through scratches and bites. The purpose of this study was to determine the B.
      henselae seroprevalence in cats in Turkey. A total of 298 cats blood samples were
      collected from six different provinces of Turkey. Sera were tested for the
      presence of anti-B. henselae IgG antibodies by indirect fluorescent antibody test
      (IFA). The seroprevalence of B. henselae was 27.9% (83/298) for the cats examined
      in this study. The seroprevalence of cats by province was significantly higher in
      Bursa (41.3%), Adana (33.9%), Aydin (27.5%) and Burdur (32.3%) than in Kayseri
      (17.9%) and Istanbul (12.5%). Statistically significant differences were not
      observed between cat sexes and living conditions of cats. The results revealed
      that B. henselae is an important zoonotic pathogen in Turkey.

PMID- 21737966
TI  - Tissue-specific expression of the calcium transporter genes TRPV5, TRPV6, NCX1,
      and PMCA1b in the duodenum, kidney and heart of Equus caballus.
AB  - Calcium transporter genes, such as transient receptor potential cation channel
      subfamily V members 5/6 (TRPV5/6), Na(+)/Ca(2+) exchanger 1 (NCX1), and plasma
      membrane calcium-transporting ATPase 1b (PMCA1b), are essential for maintaining
      homeostasis and metabolizing Ca(2+) ions. The TRPV5 and TRPV6 proteins play an
      important role in Ca(2+ )absorption, and NCX1 and PMCA1b are both critical for
      intracellular calcium homeostasis. In this study, the tissue-specific mRNA and
      protein expression of these calcium transporter genes in the duodenum, kidney and
      heart of the horse (Equus caballus) was examined using reverse transcriptase
      polymerase chain reaction (RT-PCR) and Western blot analysis. The tissue
      localization of these calcium transporters was also investigated using
      immunohistochemistry. The results showed that TRPV5 mRNA was highly expressed in
      the kidney but was scarce in the duodenum and heart. TRPV6 mRNA levels were
      similar in all the tissues. NCX1 and PMCA1b were both highly expressed in the
      heart, but no difference in NCX1 and PMCA1b mRNA expressions was observed in the
      duodenum and kidney. The aspect of protein expression was similar with mRNA
      expression data. Localization of calcium transporter genes were detected
      enterocytes in duodenum, the distal convoluted tubules in the kidney, and within
      the cardiac muscle cells of the heart. Based on these results, calcium transport
      genes appear to be expressed in horse tissues at levels similar to those observed
      in other vertebrates.

PMID- 21737967
TI  - Epidemiological survey of Theileria parasite infection of cattle in Northeast
      China by allele-specific PCR.
AB  - An epidemiological survey on a Theileria parasite infection of cattle in
      Northeast China was carried out using allele-specific PCR and DNA sequence
      analysis of the major piroplasm surface protein (MPSP) gene. The results showed
      that 14 of 104 blood samples were positive for Theileria by PCR. Among the
      positive cases, co-infection with various combinations of C- and I-type parasites
      was detected in 12 samples; no B- and Thai-type parasites were detected by allele
      specific PCR. Phylogenetic analysis based on the MPSP gene sequences revealed
      that Theileria parasites with the MPSP types 1, 2, and 4 were distributed in
      Northeast China.

PMID- 21737968
TI  - Ultrasonographic evaluation of thymus in Holstein calves and Heifers and its
      diagnostic application.
AB  - This study was performed to evaluate the cross section of the thymus in 46
      clinically healthy Holstein calves and heifers from birth to 100 weeks of age and
      8 age-matched affected animals with chronic bronchopneumonia by ultrasonography.
      The cross sectional area of the thymus increased in healthy calves and heifers
      from birth to 31 weeks of age, peaked around 35 weeks of age, and then decreased
      until 100 weeks after birth. A positive correlation (r = 0.74, P < 0.05) was
      found between the area in cross section and the weight of the whole thymus in
      calves and heifers with chronic bronchopneumonia. The cross- sectional areas of
      the thymus were significantly (P < 0.05) lowered in animals with chronic
      bronchopneumonia. The cross sections of thymus in clinically healthy calves at 2
      weeks of age and heifers at 34 weeks and 87 weeks of age were hypoechoic,
      moderately hyperechoic and hyperechoic, respectively. The observation of thymus
      by ultrasonography seems to be an effective tool for estimating the size of the
      thymus objectively in Holstein calves and heifers from birth to 100 weeks of age.
      The results of this study prove the approach to be useful and applicable to
      monitor the growth of thymus in Holstein calves and heifers and their association
      with chronic pneumonia.

PMID- 21737969
TI  - [Perspective for the research of liver disease - from basic research to clinical
      research].

PMID- 21737970
TI  - [Recent progress in the research of NASH/NAFLD in Japan].

PMID- 21737971
TI  - [Prediction of response to peg-interferon plus ribavirin therapy for chronic
      hepatitis C].

PMID- 21737972
TI  - [Treatment for elderly patients with hepatitis C virus].

PMID- 21737973
TI  - [New developed drugs for chronic hepatitis C].

PMID- 21737974
TI  - [A case of multiple gastrointestinal stromal tumors of the small intestine
      associated with von Recklinghausen disease].
AB  - A 63-year-old woman was admitted to our hospital because of tarry stool several
      years previously. At the time, cafe-au-lait spots and dermal nodules were found
      on her entire body, and a diagnosis of von Recklinghausen disease was
      established. Small bowel endoscopy revealed a submucosal tumor in the jejunum.
      Laparotomy was therefore performed on the suspicion of intestinal GIST. Numerous
      extramural tumors with a diameter of 3-5mm were observed along the jejunum and
      ileum, in addition to the primary tumor. Partial resection of the jejunum,
      including the primary tumor and only one small nodule was performed to prevent
      short bowel syndrome. Immunopathological studies of the tumors were positive for
      KIT and CD34 and we diagnosed multiple intestinal GISTs. Imatinib mesylate was
      not administered, but no growth of the residual tumors have been recognized for
      10 months after surgery.

PMID- 21737975
TI  - [A case of rectal mucosa-associated lymphoid tissue lymphoma (MALT) successfully
      treated by radiation therapy].
AB  - A 33-year-old woman had hematochezia for 5 months. A total colonoscopy showed an
      easily-bleeding elevated lesion with a nodular lesion in the lower rectum.
      Histological findings of a conventional biopsy from the lesion showed MALT
      (mucosa-associated lymphoid tissue) lymphoma and she was diagnosed as stage I.
      The monoclonality of B-cells was not detected by polymerase chain reaction
      products for immunoglobulin heavy chain. We selected antibiotic therapy because
      Helicobacter pylori was detected in culture of the patient's gastric biopsy
      specimens. The antibiotic therapy was successful, but her symptoms worsened. We
      therefore gave her with 30 Gy radiation therapy. She recovered a month after the
      radiation. Histological complete remission was confirmed 4 months after the
      radiation. Adverse events of the radiation therapy included anal pain for 1 month
      and premature ovarian failure. Radiation therapy may be useful for localized
      rectal MALT lymphoma.

PMID- 21737976
TI  - [A case of pneumatosis cystoides intestinalis induced by steroid pulse therapy
      for severe acute hepatitis B].
AB  - A 26-year-old Japanese woman was admitted to the hospital because of fever and
      general fatigue. A diagnosis of acute hepatitis B was given because of high
      levels of transaminase and positivity for HBs-Ag, HBe-Ag and HBc-IgM. On the 2nd
      day progression to fulminant hepatitis was suspected, and steroid pulse therapy,
      cyclosporin, entecavir, and interferon-beta were started. Her laboratory data
      improved until transaminase showed an increase on 18th day, and steroid was once
      again administered. Abdominal CT scan and plain abdominal X-ray showed
      pneumatosis cystoides intestinalis (PCI) mainly along the ascending colon without
      any symptoms. After discontinuation of steroid therapy, abnormal gas gradually
      disappeared. This is a very rare case of PCI, which may have been caused by short
      term steroid pulse therapy.

PMID- 21737977
TI  - [Successful chemotherapy of carcinomatosis of the bone marrow with disseminated
      intravascular coagulation from a rectal carcinoma found by eosinophilia].
AB  - A 71-year-old man with eosinophilia was given a diagnosis of poorly
      differentiated adenocarcinoma of the rectum. Further examination showed that it
      had invaded the bone marrow. He had disseminated intravascular coagulation (DIC)
      from disseminated carcinomatosis of the bone marrow after colostomy. Chemotherapy
      (mFOLFOX6) was successful and his eosinophil count, DIC score and tumor markers
      normalized. We were able to continue chemotherapy after 5 months from the
      outbreak of disseminated carcinomatosis of the bone marrow. It is said that
      disseminated carcinomatosis of the bone marrow has a poor prognosis, but we were
      able to obtain a good response in this case by chemotherapy.

PMID- 21737978
TI  - [A case of hepatic angiosarcoma detected as a small lesion].
AB  - A 72-year-old man visited for imaging examination of alcoholic cirrhosis in April
      2007. Enhanced CT images were revealed a 7 mm early enhanced lesion in segment 6
      of the liver. The lesion was increased gradually to 40 mm on MRI images 21 months
      later. We performed ultrasound liver biopsy 3 times. Histology showed
      angiosarcoma with high-grade atypia and it was positive for CD31, CD34 and factor
      VIII-related antigen. The doubling time of this tumor was 42-108 days. Although
      we performed transarterial chemoembolization and interleukin-2 therapy, the
      patient died 34 months after the initial detection of tumor. We observed the
      clinical course with periodic imaging examination from the early stage of hepatic
      angiosarcoma and obtained a pathologic diagnosis by liver biopsy.

PMID- 21737979
TI  - [Advanced gallbladder cancer that showed complete response to gemcitabine plus S
      1 chemotherapy].
AB  - A 57-year-old man with advanced gallbladder cancer and accompanying hepatic,
      colonic and duodenal invasion and para-aortic lymph node metastasis was referred
      to our hospital. Gemcitabine plus S-1 administration was chosen. Gemcitabine was
      administered intravenously at a dose of 1000 mg/m(2) on days 1 and 15, and
      repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2)
      b.i.d. on days 1-14. Chemotherapy was effective for the primary gallbladder tumor
      and lymph node metastasis. The primary tumor and metastatic lymph nodes were
      shown to have disappeared by a FDG-PET CT study after 10 courses of chemotherapy.
      Informed consent was obtained prior to performing surgery of the primary lesion.
      Pathological examination showed fibrosis and a small focus of residual cancer in
      the resected gallbladder. Complete resection was achieved as all the margins were
      negative. The findings suggest that gemcitabine plus S-1 treatment may be
      effective against advanced gallbladder cancer.

PMID- 21737980
TI  - [A case of hilar bile duct cancer which recurred at abdominal and cervical lymph
      nodes 8 years after curative resection].
AB  - A 40-year-old man underwent right hemihepatectomy with biliary reconstruction for
      hilar bile duct cancer, and the surgical margin being negative. The tumor,
      showing atypical intraductal growth, was solid adenocarcinoma with rich mucinous
      component, although it was negative for MUC1, MUC2 and MUC5AC, suggesting that
      the tumor was not an intraductal papillary neoplasm of the bile duct (IPN-B).
      Eight years after operation, abdominal and cervical lymph node metastases were
      found on computed tomography and (18)F-deoxyglucose positron emission tomography
      examination. Late remote recurrence after curative resection of the extrahepatic
      bile duct cancer is relatively rare. The recurrence in the present case maybe
      explained by the tumor dormancy theory.

PMID- 21737981
TI  - [A case of mucinous cystadenoma of the pancreas resected after a 10-year follow
      up].
AB  - A 40-year-old woman was hospitalized because of acute pancreatitis. CT showed a
      monolocular cyst thought to be a pseudocyst. The patient was followed as an
      outpatient. The size of the cyst decreased 6 years later. Ultrasonography 10
      years later demonstrated an enlarged cyst with a cyst-in-cyst formation. A
      tendency to increase in size and the irregular wall thickening indicated that the
      cyst was a malignant mucinous cystic neoplasm (MCN) and distal pancreatectomy was
      performed. The tumor was diagnosed histologically as a mucinous cystadenoma. A
      case of MCN resected after long-term follow-up is extremely rare. The present
      case is thought to be important for elucidation of the natural history of MCNs.

PMID- 21737982
TI  - [Frequent inactivation of A20 through gene mutation in B-cell lymphomas].

PMID- 21737983
TI  - [Analysis of leukemogenesis induced by C/EBPalpha mutations].

PMID- 21737984
TI  - [Hes1 immortalizes committed progenitors and plays a role in blast crisis
      transition of chronic myelogenous leukemia].

PMID- 21737985
TI  - [Acquired uniparental disomy and c-CBL mutation in myelodysplastic syndromes].

PMID- 21737986
TI  - [Pathophysiology of immune thrombocytopenia].

PMID- 21737987
TI  - [Pleiotropic effects of thrombomodulin in the management of DIC].

PMID- 21737988
TI  - [Gene and cell therapy for hemophilia: recent advances].

PMID- 21737989
TI  - [Regulation of erythropoiesis by hypoxia inducible factors (HIFs)].

PMID- 21737990
TI  - [Structure and dynamics of gene regulatory network for humoral immune response].

PMID- 21737991
TI  - [GDF15 expression and iron overload in ineffective erythropoiesis].

PMID- 21737992
TI  - [Signaling in iron metabolism via transferrin receptor 2: significance in
      erythropoiesis].

PMID- 21737993
TI  - [Phase I study of nelarabine in patients with relapsed or refractory T-ALL/T
      LBL].
AB  - The safety, tolerability, pharmacokinetics and efficacy of nelarabine were
      evaluated in adult and pediatric patients with relapsed or refractory T-ALL/T
      LBL. Adult patients received nelarabine i.v. over 2 hours on days 1, 3 and 5 in
      every 21 days, and pediatric patients received this regimen over 1 hour for 5
      consecutive days in every 21 days. Safety was evaluated in 7 adult and 6
      pediatric patients. Adverse events (AEs) were reported in all patients. Most
      frequently reported AEs included somnolence and nausea in adult patients and
      leukopenia and lymphocytopenia in pediatric patients. Five grade 3/4 AEs were
      reported in both adult and pediatric patients, most of which were hematologic
      events. There were no dose-limiting toxicities. Efficacy was evaluated in 7 adult
      and 4 pediatric patients. Complete response was noted in 1 adult and 2 pediatric
      patients. Higher intracellular ara-GTP concentrations were suggested to be
      associated with efficacy. Japanese adult and pediatric patients with T-ALL/T-LBL
      well tolerated nelarabine treatment, warranting further investigation.

PMID- 21737994
TI  - The association of epicardial fat thickness with blunted heart rate recovery in
      patients with metabolic syndrome.
AB  - Epicardial fat tissue has unique endocrine and paracrine functions that affect
      the cardiac autonomic system. Epicardial fat thickness (EFT) and blunted heart
      rate recovery (HRR) are newly identified cardiovascular risk factors in patients
      with metabolic syndrome (MS). The objective of this study is to evaluate the
      association between EFT and HRR in patients with MS. Forty patients with MS and
      36 healthy controls were included in the study. Echocardiographic EFT and HRR at
      1min after exercise termination (HRR-1) are measured and compared between the two
      groups. HRR-1 equal to or lower than 18 beats is considered as blunted HRR. EFT
      was increased (7.2 +/- 2 vs. 5.6 +/- 1.8 mm; p = 0.001) and HRR-1 was
      significantly reduced in patients with MS compared to control group (21 +/- 8 vs.
      26 +/- 9; p = 0.006). Among the MS patients, subjects with blunted HRR had
      increased EFT compared to patients without blunted HRR (8.5 +/- 2.0 vs. 5.9 +/-
      1.1 mm, p < 0.001). In multivariate analysis, EFT was the only independent
      predictor of blunted HRR in patients with MS (95% confidence interval = 1.42
      3.87, OR = 2.34, p = 0.001). Furthermore, EFT of equal to or thicker than 5.5 mm
      was associated with the blunted HRR with 84% sensitivity and 52% specificity (ROC
      area under curve: 0.84, 95% confidence interval = 0.70-0.96, p < 0.001). In
      conclusion, EFT is an independent predictor of blunted HRR, a novel
      cardiovascular risk factor, in patients with MS.

PMID- 21737995
TI  - Down-regulation of ATP-binding cassette transporter G1 expression by unmethylated
      CpG oligodeoxynucleotides in RAW 264.7 macrophages.
AB  - We have investigated the effect of various forms of phosphodiester cytidine
      phosphate-guanosine oligodeoxynucleotides (CpG ODNs) on the production of pro
      inflammatory cytokines and related genes in RAW 264.7 macrophages. Treatment with
      the CpG ODNs increased the expression of tumor necrosis factor alpha (TNF-alpha),
      IL-6, and inducible nitric oxide synthase but not interleukin-1beta (IL-1beta).
      We also investigated the effect of CpG ODNs on the expression of ATP-binding
      cassette transporter A1 (ABCA1) and G1 (ABCG1) genes which are known to
      facilitate cholesterol efflux from macrophages for anti-atherosclerosis. CpG 2006
      significantly reduced the levels of ABCG1 mRNA as determined by real-time
      polymerase chain reaction, whereas ABCA1 mRNA level was not changed. Western blot
      analysis further confirmed the reduction of ABCG1 protein expression by CpG 2006.
      In addition, we also determined the protein level of peroxisome proliferator
      activated receptor gamma (PPARgamma), which is recognized as a transcriptional
      activator of ABC transporters, was also reduced by CpG 2006. Thus, these results
      suggest that ABCG1 is specifically down-regulated by CpG 2006 in a PPARgamma
      dependent manner in macrophages.

PMID- 21737996
TI  - Hypovitaminosis D in geriatric inpatients: a marker of severity of chronic
      diseases.
AB  - BACKGROUND AND AIMS: Hypovitaminosis D is associated with adverse health outcomes
      including several bone and non-bone chronic diseases. It remains unclear whether
      hypovitaminosis D leads to more numerous or more severe chronic diseases. Our aim
      was to determine whether there was an association between serum 25-hydroxyvitamin
      D deficiency (i.e., 25OHD <=25 nmol/L) and, respectively, the number and severity
      of chronic diseases assessed with the Kaplan- Feinstein index (KFI) among
      geriatric inpatients. METHODS: Two hundred and forty older Caucasian adults
      admitted between December 2008 and September 2009 to the geriatric acute care
      unit of Angers University Hospital, France (mean 84.6+/-0.4 years; 68.8% women)
      were included in this cross-sectional study. Serum 25OHD, KFI score and number of
      chronic diseases (i.e., diseases lasting at least 3 months or running a course
      with minimal change, whatever their nature or site) were assessed. Subjects were
      divided into 2 groups according to 25OHD concentration (either deficient for
      25OHD <=25 nmol/L, or non-deficient for 25OHD >25 nmol/L). Age, gender, use of
      vitamin D supplements, number of chronic diseases, serum parathyroid hormone and
      season tested were used as potential confounders. RESULTS: Mean serum 25OHD
      concentration was 35.2 +/- 1.7 nmol/L. The 102 (42.5%) subjects with 25OHD
      deficiency had higher KFI compared with their counterparts (p=0.008). Vitamin D
      deficiency was not significantly associated with the number of chronic diseases
      (adjusted beta=-0.37 with p=0.216), but with KFI (unadjusted beta=1.33 with
      p=0.008; adjusted beta=1.37 with p=0.010). CONCLUSIONS: Irrespective of the
      number of chronic diseases, 25OHD deficiency was associated with the severity of
      chronic diseases.

PMID- 21737997
TI  - Differences between subjects with sufficient and deficient urinary iodine in an
      area of iodine sufficiency.
AB  - BACKGROUND: Iran has long been recognized as a country of iodine sufficiency;
      however, recent studies show that the proportion of subjects with insufficient
      urinary iodine is gradually increasing in Tehran capital city. AIM: The aim of
      this study was to evaluate differences between individuals with sufficient and
      deficient urinary iodine in Tehran. MATERIAL AND METHODS: In this cross-sectional
      study, 639 Tehranian adult subjects, aged >= 19 yr (242 males, 397 females), were
      enrolled through randomized cluster sampling. A 24-h urine sample was collected
      for measurement of urinary iodine, sodium and creatinine concentrations using the
      digestion method, flame photometry and autoanalyzer assay, respectively. Salt
      intake was estimated and iodine content of household salt was measured by
      titration. RESULTS: Medians (interquartile range) of 24-h urinary iodine
      concentrations in subjects with sufficient and deficient urinary iodine were
      163.0 (126.0-235.0) and 44.0 (26.0-67.0) MUg/l, p<0.001, respectively. Salt with
      iodine content of >20 parts per million was consumed by 77.4 and 38.3% of
      subjects with sufficient and deficient urinary iodine, respectively (p<0.001).
      Median daily salt intake in subjects with sufficient urinary iodine was
      significantly higher than in those with deficient urinary iodine (8.1 vs 7.3 g,
      p<0.001). No significant differences in the mentioned variables were observed
      between males and females. Fifty and 30% of subjects with insufficient and
      sufficient urinary iodine had <7 yr education, respectively (p<0.001).
      CONCLUSIONS: Iodine content of salt, the amount of salt intake and education
      levels differ greatly between subjects with sufficient and deficient urinary
      iodine in Tehran.

PMID- 21737998
TI  - Assessment of body fat composition disturbances by bioimpedance analysis in HIV
      infected adults.
AB  - HIV-lipodystrophy syndrome is characterized by different patterns of body fat
      distribution (BFD) which are identified by clinical and body composition (BC)
      assessment, including bioimpedance analysis (BIA). Our aim was to compare BC in
      HIV-infected patients on combination antiretroviral therapy (cART) according to 4
      distinct phenotypes of BFD (G1-no lipodystrophy, G2-isolated central fat
      accumulation, G3-lipoatrophy, G4-mixed forms of lipodystrophy) and assessed
      factors associated with them. Anthropometry and BIA were performed in 344 HIV-1
      patients. G2 and G4 phenotype patients had significantly higher fat mass (FM) but
      no differences were observed in fat-free mass (FFM) and total body water among
      the 4 phenotypes. Significant negative associations were found between the
      presence of lipoatrophy and female gender, body mass index (BMI), waist (WC), hip
      (HC) and thigh circumferences, and total body FM estimated by BIA. After
      adjustment for gender, cART duration and BMI, G3 had significant lower WC [odds
      ratio (OR)=0.84; 0.78- 0.90] and HC (OR=0.88; 0.81-0.96) mean. Independently of
      gender, cART duration and BMI, G2 remained significantly associated with higher
      WC (OR=1.11; 1.05-1.18) and HC (OR=1.15; 1.07-1.23) mean, and with FM estimated
      by BIA [FM as %, OR=1.17 (1.09-1.26); and FM as kg, OR=1.15 (1.06- 1.25)]. There
      was a significant positive association between G4 and female gender (OR=1.66;
      1.01-2.75), BMI (OR=1.10; 1.04-1.17) and WC (OR=1.15; 1.09-1.21). The similar FFM
      along the BFD spectrum describes the actual BC of these patients without
      sarcopenia. In a clinical setting, BIA is an easy and useful tool to evaluate fat
      mass and FFM and gives us a picture of BC that was not possible with
      anthropometry.

PMID- 21737999
TI  - Relationship between metabolic syndrome and multinodular non-toxic goiter in an
      inpatient population from a geographic area with moderate iodine deficiency.
AB  - BACKGROUND: Obesity and insulin resistance predispose individuals to the
      development of both metabolic syndrome and non-toxic nodular thyroid diseases.
      AIM: The aim of this observational, cross-sectional study is to evaluate the
      relationship between metabolic syndrome and multinodular nontoxic goiter in an
      inpatient population from a geographic area with moderate iodine deficiency.
      SUBJECTS AND METHODS: We examined 1422 Caucasian euthyroid inpatients. Thyroid
      volume was determined by ultrasound of the neck. A fine-needle aspiration biopsy
      was performed to evaluate single thyroid nodules and dominant nodules >=15 mm in
      euthyroid multinodular goiter. The diagnosis of metabolic syndrome was made
      according to the criteria of the American Heart Association/ National Heart,
      Lung, and Blood Institute. RESULTS: Of the sample, 277 patients had clinical
      evidence of multinodular nontoxic goiter, 461 met the criteria for the diagnosis
      of metabolic syndrome, and 132 were found to have both conditions. After
      adjusting for age, gender, body mass index, nicotinism, parity, alcohol intake,
      thyroid function, and metabolic syndrome- related pharmacological treatment,
      metabolic syndrome was found to be an independent risk factor for the occurrence
      of multinodular non-toxic goiter. The relationship between metabolic syndrome and
      multi nodular non-toxic goiter was apparent in both men and women. CONCLUSIONS:
      In this study of euthyroid inpatients, we demonstrate that metabolic syndrome is
      an independent risk factor for the occurrence of multinodular non-toxic goiter in
      a geographic area with moderate iodine deficiency. We propose that patients
      meeting the criteria for metabolic syndrome should be screened for the presence
      of multinodular non-toxic goiter.

PMID- 21738000
TI  - Principles and clinical applications of liquid chromatography - tandem mass
      spectrometry for the determination of adrenal and gonadal steroid hormones.
AB  - Liquid-chromatography - tandem mass spectrometry (LC-MS/MS) is becoming the
      method of choice for clinical steroid analysis. In most instances, it has the
      advantage of higher sensitivity, better reproducibility and greater specificity
      than commercial immunoassay techniques. The method requires only minimal sample
      preparation and a small sample volume. Furthermore, it has the potential to
      analyze multiple steroids simultaneously. Modern instruments guarantee high
      throughput, allowing an affordable price for the individual assay. All this makes
      LC-MS/MS an attractive method for use in a clinical setting. Reliable reference
      ranges for the detected analytes are the pre-requisite for their clinical use. If
      these are available, LC-MS/MS can find application in congenital disorders of
      steroid metabolism, such as congenital adrenal hyperplasia, disorders of sex
      development and disorders of salt homeostasis, as well as in acquired disorders
      of steroid metabolism, such as primary aldosteronism, Cushing's disease,
      Addison's disease, and hyperandrogenemia, as well as in psychiatric disease
      states such as depression or anxiety disorders. The principles of LC-MS/MS for
      steroid measurement, the pros and cons of LC-MS/MS compared with conventional
      immunoassays and the possible applications in clinical routine, with a special
      focus on pediatric endocrinology needs, are discussed here.

PMID- 21738001
TI  - Clinical and biochemical impact of BCL1 polymorphic genotype of the
      glucocorticoid receptor gene in patients with adrenal incidentalomas.
AB  - BACKGROUND: Adrenal incidentaloma (AI) is a common clinical problem. Subtle
      hormonal abnormalities are present in a substantial proportion of patients. BCL1
      gene polymorphism of the glucocorticoid receptor (GR) is associated with
      increased sensitivity to glucocorticoid action. The genotype- phenotype
      associations of this polymomorphism in patients presenting with AI has not been
      extensively investigated. AIM: A cross-sectional study in secondary/tertiary care
      centers. SUBJECTS/METHODS: Ninety-five subjects with AI were genotyped for the
      BCL1 GR gene polymorphism. Patients underwent an oral glucose tolerance test and
      a dexamethasone suppression test (DST). The presence of subclinical
      hypercortisolism, features of metabolic syndrome, and osteoporosis/ osteopenia
      were also assessed. RESULTS: No significant differences in markers of adrenal
      function between BCL1 carriers and non-carriers were revealed. Also, no
      difference was found in the features of metabolic syndrome, as well as in bone
      metabolism and density between these 2 groups. However, DST suppressor patients
      belonged more frequently to the BCL1 carriers group (41 out of 69 patients, 59.4%
      vs 9 out of 26 patients, 34.6%, p=0.0039), had smaller total adenoma size (2.4+/
      0.2 cm vs 3.5+/-0.4 cm, p=0.04), and lower incidence of bilateral adrenal masses
      (18.8% vs 46.2%, p=0.01). CONCLUSIONS: AI patients who also carry the polymorphic
      BCL1 variant exhibit smaller size adrenal nodules. Those AI patients with
      complete DST suppression had a higher incidence of the polymorphic BCL1 variant.
      However, this study failed to demonstrate any significant impact of BCL1 GR
      polymorphism on the frequency of cortisol-dependent co-morbidities in patients
      with AI.

PMID- 21738002
TI  - Glucose metabolism among residents in Shanghai: natural outcome of a 5-year
      follow-up study.
AB  - BACKGROUND: Previous studies have shown that Type 2 diabetes mellitus (T2DM) is
      usually preceded by a condition known as pre-diabetes. However, few studies
      evaluate the rate of each status of impaired glucose regulation progressed to
      T2DM and its related metabolic disorders impacting the development. AIM: To
      investigate the natural outcome of glucose metabolism among Shanghai adult
      residents during a 5-yr period, and estimate the metabolic characteristics
      related with the conversion of glucose tolerance. SUBJECTS AND METHODS: A cross
      sectional survey with multiple- stage and random sampling was conducted among
      1869 adult residents from Shanghai Pudong New District in 2002. In 2007, 1042 non
      diabetic subjects were successfully followed up. All the participants completed a
      questionnaire and underwent anthropometric measurements and a 75-g oral glucose
      tolerance test. RESULTS: The incidence of diabetes was higher in isolated
      impaired glucose tolerance (i- IGT), isolated impaired fasting glucose (i-IFG),
      and combined fasting and post-prandial hyperglycemia (IFG/IGT) group when
      compared to that in normal glucose tolerance group, as relative ratios with 95%
      confidence intervals of 9.2 (5.5- 15.2), 7.5 (3.6-15.7), and 13.2 (5.8-30.2),
      respectively. Subjects who had 2 or more metabolic disorders had a 2-3-fold
      higher incidence than those with less than 1 metabolic disorder (all p<0.001).
      CONCLUSIONS: People with pre-diabetes are at increased risk of diabetes,
      suggesting the need for frequent screening in theloe people with several
      metabolic disorders.

PMID- 21738003
TI  - Association of two glyoxalase I gene polymorphisms with nephropathy and
      retinopathy in Type 2 diabetes.
AB  - BACKGROUND: Glyoxalase I (GLO1), which is the major enzyme that catalyzes the
      metabolism of methylglyoxal (MG), may play an important role in the pathogenesis
      of diabetic microvascular complications. AIM: To investigate whether the C-7T and
      A419C polymorphisms of the GLO1 gene are associated with nephropathy and
      retinopathy in Chinese Type 2 diabetic patients. SUBJECTS AND METHODS: A total of
      364 Type 2 diabetic patients and 301 healthy controls were enroled in the study.
      Diabetic microvascular complications were determined by urinary albumin excretion
      measurements and ophthalmological examinations. Genetic analyses were performed
      using either Taqman PCR or direct sequencing. The effect of C-7T polymorphism on
      promoter activity was measured by reporter gene assays. RESULTS: The albumin/
      creatinine ratio (ACR) and prevalence of nephropathy and retinopathy were
      significantly higher in diabetic patients with GLO1 -7CC genotype than in
      patients with -7CT and -7TT genotypes (p=0.02, p=0.02, and p=0.04, respectively).
      The - 7CC genotype is independently associated with ACR (beta=0.13, p=0.01) and
      the risk for retinopathy [odds ratio (OR): 2.30, 95% confidence interval (CI):
      1.25-4.24, p<0.01]. The luciferase activity of the -7T promoter was higher than
      that of the -7C promoter (13.2+/-0.2 vs 11.7+/-0.8, p=0.04). No differences were
      found between ACR and the prevalence of nephropathy and retinopathy for A419C
      polymorphism in Type 2 diabetic patients. CONCLUSIONS: GLO1 C-7T polymorphism
      alters promoter activity and confers susceptibility to nephropathy and
      retinopathy to Type 2 diabetic patients.

PMID- 21738004
TI  - Resveratrol, an effective regulator of ovarian development and oocyte apoptosis.
AB  - Resveratrol, a phytopolyphenol compound found chiefly in grapes and wine, has
      been reported to have a variety of anti-inflammatory, anti-platelet, and anti
      carcinogenic effects. However, little is known about the effects of resveratrol
      on ovarian development and oocyte apoptosis. We investigated the effects of
      resveratrol on ovarian development in rats with different ages [from post-natal
      day (PD) 1 to 15 months], as well as on oocyte apoptosis in PD1 and PD2 rat
      ovaries. We show that: a) ip injection of resveratrol (20 mg/kg/day) increased
      the percentage of unassembled follicles and the total number of oocytes in PD1
      and PD2 rat ovaries. Similar results were obtained when mothers were treated with
      resveratrol (20 mg/kg/day) by intragastric administration from day 11, after the
      detection of vaginal plug, until delivery. In PD4 rat ovaries, the total number
      of oocytes was significantly increased in the groups treated with resveratrol.
      Moreover, more unassembled follicles and fewer primary follicles were present in
      the groups treated with resveratrol than in the controls; b) in 15-month-old rat
      ovaries, resveratrol increased the number of resting follicles and total oocytes,
      and decreased the number of developing follicles and atretic follicles; 3) the
      percentage of TUNEL-positive oocytes decreased in PD1 and PD2 rat ovaries after
      resveratrol treatment, and the number of oocytes positive for Foxo3a, Bim, and
      p27KIP1 in PD2 rat ovaries was lower in the resveratrol treatment group than in
      controls. These results suggest that resveratrol may delay oocyte nest breakdown
      and inhibit both the primordial-to-developing-follicle transition and apoptosis
      by decreasing the activation of Foxo3a, Bim, and p27KIP1, thus augmenting the
      resting follicle reserves, maintaining regular estrous cycles of early aged rats
      and delaying climacterium.

PMID- 21738005
TI  - Elevated body mass index correlates with higher seminal plasma interleukin 8
      levels and ultrasonographic abnormalities of the prostate in men attending an
      andrology clinic for infertility.
AB  - BACKGROUND: Obesity is associated with a systemic, low-grade inflammatory state.
      Although the relationship between obesity and semen parameters or prostate
      diseases has been previously investigated, the association between body mass
      index (BMI), prostate inflammatory diseases and color- Doppler ultrasound (CDU)
      of the male genital tract (MGT) has been poorly studied. AIM: To evaluate the
      association between BMI and CDU features of the MGT, signs and symptoms of
      prostate inflammation, semen parameters. MATERIALS/SUBJECTS AND METHODS: We
      studied 222 men seeking medical care for couple infertility. According to the
      World Health Organization classification, subjects were divided into 3 groups:
      normal weight (no.=131, BMI=18.5-24.9 kg/m2), overweight (no.=71, BMI=25.0-29.9
      kg/m2), obese (no.=20, BMI>=30.0 kg/m2). All patients underwent simultaneous
      testosterone evaluation and seminal analysis, including interleukin 8 (sIL-8),
      along with scrotal and transrectal CDU, before and after ejaculation. Prostatitis
      symptoms were evaluated by National Institutes of Health- Chronic Prostatitis
      Symptom Index questionnaire. RESULTS: After adjusting for age and testosterone
      levels, higher BMI was significantly related to higher prostate volume and
      several CDU features of the prostate, including macro-calcifications,
      inhomogeneity, higher arterial peak systolic velocity (the latter adjusted also
      for blood pressure), but not with abnormalities of testis, epididymis, seminal
      vesicles. Furthermore, higher BMI and BMI class were significantly related to
      higher sIL-8, a reliable surrogate marker of prostate inflammatory diseases, even
      after adjustment for age. Conversely, no associations among BMI, clinical
      symptoms of prostatitis or semen parameters were observed. CONCLUSIONS: Subjects
      with higher BMI might develop CDU and biochemical signs suggestive of prostate
      inflammation, although not clinically overt.

PMID- 21738006
TI  - The DNA damage mark pH2AX differentiates the cytotoxic effects of small molecule
      HDAC inhibitors in ovarian cancer cells.
AB  - High grade epithelial ovarian cancers are relatively sensitive to DNA damaging
      platinum-based chemotherapy, suggesting that the dependencies of ovarian tumors
      on DNA damage response pathways can be harnessed for therapeutic purposes. Our
      goal was to determine if the DNA damage mark gamma-H2AX phosphorylation (pH2AX)
      could be used to identify suitable cytotoxic histone deacetylase inhibitors
      (HDACi) for ovarian cancer treatment. Nineteen chemically diverse HDACi compounds
      were tested in 7 ovarian cancer cell lines. Fluorescent, biochemical and cell
      based assays were performed to assess DNA damage by induction of pH2AX and to
      measure cell viability and apoptosis. The relationships between pH2AX and the
      cellular effects of cell viability and apoptosis were calculated. Selected HDACi
      were tested in combination with cisplatin and other DNA damaging agents to
      determine if the HDACi improved upon the effects of the DNA damaging agents. The
      HDACi compounds induced differing levels of pH2AX expression. High levels of
      pH2AX in HDACi-treated ovarian cancer cells were tightly associated with
      decreased cell viability and increased apoptosis. Consequently, a ketone-based
      HDACi was chosen and found to enhance the effects of cisplatin, even in ovarian
      cancer cells with extreme resistance to DNA damaging drugs. In conclusion, a
      fluorescent-based assay for pH2AX can be used to determine cellular responses to
      HDACi in vitro and may be a useful tool to identify potentially more effective
      HDACi for the treatment of ovarian cancer. In addition, these results lend
      support to the inclusion of ketone-derived HDACi compounds for future
      development.

PMID- 21738007
TI  - Interaction of the ARF tumor suppressor with cytosolic HSP70 contributes to its
      autophagy function.
AB  - The p14/p19 (ARF)  (ARF) tumor suppressor gene is frequently mutated in human
      cancer. Recently ARF has been shown to localize to mitochondria and to induce
      autophagy. However the controls that regulate the trafficking of ARF to
      mitochondria remain unknown. We recently reported that 2-phenylethynesulfonamide
      (PES) selectively interacts with cytosolic heat shock protein 70 (HSP70) and
      inhibits its function; we further showed that PES promotes the death of tumor
      cells, and that this is associated with an impairment of lysosome function and an
      inhibition of autophagy. In the present work we used a mass spectrometry-based
      approach to identify mitochondrial ARF-binding proteins. We report that
      mitochondrial ARF interacts with HSP70. We show that treatment of cells with PES
      blocks the trafficking of ARF to mitochondria, indicating that interaction with
      HSP70 mediates the mitochondrial localization of ARF. We also show that PES
      inhibits the ability of ARF to induce autophagy, supporting the premise that
      localization to this organelle is critical for ARF-induced autophagy. Finally, we
      report that cells expressing high levels of ARF are more sensitive to PES than
      counterparts with ARF silenced. High levels of ARF are characteristic of tumor
      cells with enhanced MAPK signaling and advanced stage; therefore, these data
      support the premise that PES may show preferential cytotoxicity to advanced stage
      cancers.

PMID- 21738008
TI  - Augmentation of NVP-BEZ235's anticancer activity against human lung cancer cells
      by blockage of autophagy.
AB  - Autophagy is a cellular lysosomal degradation pathway essential for regulation of
      cell survival and death to maintain homeostasis. This process is negatively
      regulated by mammalian target of rapamycin (mTOR) signaling and often counteracts
      efficacy of certain cancer therapeutic agents. NVP-BEZ235 (BEZ235) is a novel,
      orally bioavailable dual PI3K/mTOR inhibitor that has exhibited promising
      activity against non-small cell lung cancer (NSCLC) in preclinical models. The
      current study focuses on evaluating the role of BEZ235 in regulating autophagy.
      BEZ235 was effective in inhibiting the growth of NSCLC cells including induction
      of apoptosis. It also potently induced the expression of type-II LC3, indicating
      induction of autophagy. When BEZ235 was used in combination with the lysosomal or
      autophagic inhibitor chloroquine (CQ), enhanced inhibitory effects on monolayer
      growth and colony formation of NSCLC cells was observed. In addition, enhanced
      induction of apoptosis was also detected in cells exposed to the combination of
      BEZ235 and CQ. Moreover, the combination of BEZ235 and CQ was more effective than
      each single agent alone in inhibiting the growth of NSCLC xenografts in nude
      mice. Thus, induction of autophagy by BEZ235 appears to be a survival mechanism
      that may counteract its anticancer effects. Based on these, we suggest a strategy
      to enhance BEZ235's anticancer efficacy by blockade of autophagy.

PMID- 21738009
TI  - The cellular prion protein with a monoacylated glycosylphosphatidylinositol
      anchor modifies cell membranes, inhibits cell signaling and reduces prion
      formation.
AB  - The prion diseases occur following the conversion of the cellular prion protein
      (PrPC) into a disease-related isoform (PrPSc). In this study a cell painting
      technique was used to examine the role of the glycosylphosphatidylinositol (GPI)
      anchor attached to PrPC in prion formation. The introduction of PrPC to infected
      neuronal cells increased the cholesterol content of cell membranes, increased
      activation of cytoplasmic phospholipase A2 (cPLA2) and increased PrPSc formation.
      In contrast, PrPC with a monoacylated GPI anchor did not alter the amount of
      cholesterol in cell membranes, was not found within lipid rafts and did not
      activate cPLA2. Although monoacylated PrPC remains within cells for longer than
      native PrPC it was not converted to PrPSc. Moreover, the presence of monoacylated
      PrPC displaced cPLA2 from PrPSc-containing lipid rafts, reducing the activation
      of cPLA2 and PrPSc formation. We conclude that acylation of the GPI anchor
      attached to PrPC modifies the local membrane microenvironments that control some
      cell signaling pathways, the trafficking of PrPC and PrPSc formation. In
      addition, such observations raise the possibility that the pharmacological
      modification of GPI anchors might constitute a novel therapeutic approach to
      prion diseases.

PMID- 21738010
TI  - Drosophila immunity research on the move.
AB  - Drosophila has been established as useful model for infectious diseases because
      it allows large numbers of whole animals to be studied and provides powerful
      genetic tools and conservation with signaling and pathogenesis mechanisms in
      vertebrates. During the past twenty years, significant progress has been made on
      the characterization of innate immune responses against various pathogenic
      organisms in flies (Fig. 1). In this year's Drosophila Research Conference, which
      was held in San Diego (March 30-April 3) and sponsored by the Genetics Society of
      America, the immunity and pathogenesis session comprised seven platform
      presentations and 34 posters that highlighted the latest advances in Drosophila
      infection and immunity field. The presented work covered a wide range of studies
      from immune signaling pathways and the molecular basis of humoral and cellular
      immune mechanisms to the role of endosymbionts in fly immune function and effects
      of immune priming. Here, we give an overview of the presented work and we explain
      how these findings will open new avenues in Drosophila immunity research.

PMID- 21738011
TI  - Membrane curvature response in autophagy.
AB  - Membrane trafficking is key for signal transduction, cargo transportation, and in
      the case of autophagy, delivering cytoplasmic substrates to the lysosome for
      degradation. Autophagy requires the formation of a unique double membrane
      vesicle, the autophagosome. However, the mechanism by which the autophagosome
      forms is unknown. Our recent study focused on the role of Barkor/Atg14(L) in
      targeting the autophagy-specific class III phosphatidylinositol-3-kinase
      (PtdIns3KC3) complex to the early autophagosome has implicated this complex in
      autophagosome formation. This study found that the BATS domain of Barkor targets
      the PtdIns3KC3 complex to early autophagic structures and senses highly curved
      membranes enriched in phosphatidylinositol-3-phosphate (PtdIns(3)P).
      Consequently, this study uncovered an exciting new role for the PtdIns3KC3
      complex as a potential inducer of autophagosome formation.

PMID- 21738012
TI  - Involvement of mitophagy in oncogenic K-Ras-induced transformation: overcoming a
      cellular energy deficit from glucose deficiency.
AB  - Although mitochondrial impairment has often been implicated in carcinogenesis,
      the mechanisms of its development in cancer remain unknown. We report here that
      autophagy triggered by oncogenic K-Ras mediates functional loss of mitochondria
      during cell transformation to overcome an energy deficit resulting from glucose
      deficiency. When Rat2 cells were infected with a retrovirus harboring
      constitutively active K-Ras (V12) , mitochondrial respiration significantly
      declined in parallel with the acquisition of transformation characteristics.
      Decreased respiration was not related to mitochondrial biogenesis but was
      inversely associated with the increased formation of acidic vesicles enclosing
      mitochondria, during which autophagy-related proteins such as Beclin 1, Atg5, LC3
      II and vacuolar ATPases were induced. Interestingly, blocking autophagy with
      conventional inhibitors (bafilomycin A, 3-methyladenin) and siRNA-mediated
      knockdown of autophagy-related genes recovered respiratory protein expression and
      respiratory activity; JNK was involved in these phenomena as an upstream
      regulator. The cells transformed by K-Ras (V12)  maintained cellular ATP level
      mainly through glycolytic ATP production without induction of GLUT1, the low Km
      glucose transporter. Finally, K-Ras (V12) -triggered LC3-II formation was
      modulated by extracellular glucose levels, and LC3-II formation increased only in
      hepatocellular carcinoma tissues exhibiting low glucose uptake and increased K
      Ras expression. Taken together, our observations suggest that mitochondrial
      functional loss may be mediated by oncogenic K-Ras-induced mitophagy during early
      tumorigenesis even in the absence of hypoxia, and that this mitophagic process
      may be an important strategy to overcome the cellular energy deficit triggered by
      insufficient glucose.

PMID- 21738013
TI  - Section E9 of the American College of Medical Genetics technical standards and
      guidelines: fluorescence in situ hybridization.
AB  - This updated Section E9 has been incorporated into and supersedes the previous
      Section E9 in Section E: Clinical Cytogenetics of the 2008 Edition (Revised
      02/2007) American College of Medical Genetics Standards and Guidelines for
      Clinical Genetics Laboratories. This section deals specifically with the
      standards and guidelines applicable to fluorescence in situ hybridization
      analysis.

PMID- 21738016
TI  - Dose-dependent neurologic abnormalities in workers exposed to 1-bromopropane.

PMID- 21738017
TI  - Comparative effectiveness research: do employers care? What will they do? What
      about productivity outcomes?

PMID- 21738018
TI  - What is the role of emergency management in occupational medicine?

PMID- 21738021
TI  - "Blowing up the barriers" in surgical training: exploring and validating the
      concept of distributed simulation.
AB  - OBJECTIVES: To explore face, content and construct validity of Distributed
      Simulation (DS), an innovative approach to low-cost, high-fidelity surgical
      simulation and compare technical performance in the DS with that on a standard
      surgical box trainer. BACKGROUND: Immersive simulation is widely accepted as an
      important modality for surgical education. However, access and cost limit the
      uptake of full-scale simulation training. DS is a portable, simulated clinical
      environment aiming at widening access to immersive simulation. METHODS: Ten
      novice and 10 expert surgeons performed a laparoscopic cholecystectomy on a
      porcine model in the DS and on a box trainer. Face and content validity were
      measured using 6-point Likert-type questionnaires. Construct validity was rated
      using the Objective Structured Assessment of Technical Skills (OSATS). Comparison
      of technical performance between DS and box trainer was measured using the
      Wilcoxon test. RESULTS: Face validity was rated as 5.1 (SD = 0.54) by novices and
      4.8 (SD = 0.64) by experts.Content validity was rated as 5.2 (SD = 0.40) by
      novices and 5.1 (SD = 0.56) by experts. Experts performed significantly better
      than novices in the DS (16.3 vs. 27.3, P < 0.001) demonstrating construct
      validity. Experts' technical performance did not differ between DS and box
      trainer (26.5 vs. 27.3, P > 0.84) whereas novices performed better on the box
      trainer (19.8 vs. 16.3, P < 0.01). Qualitative data analysis demonstrated that
      surgeons felt able to behave as if in a real operating room (OR). CONCLUSION: DS
      offers a valid, low-cost, accessible environment for training and assessing
      surgeons. This approach has major implications for surgical education and for the
      widespread implementation of immersive simulation at a time of increasing
      financial austerity.

PMID- 21738022
TI  - Phenotypic variability in a three-generation Northern Irish family with Sotos
      syndrome.
AB  - Sotos syndrome is an overgrowth disorder with autosomal dominant inheritance
      caused by mutations and deletions in the nuclear receptor Set domain-containing
      protein 1 gene. In general, affected individuals have an advanced bone age,
      macrocephaly, characteristic facial gestalt and learning difficulties. Genotype
      phenotype correlations are unclear. Full penetrance is seen and 95% of cases are
      de novo. Here, we report a three-generation pedigree, with at least eight
      affected individuals, shown to harbour the nuclear receptor Set domain-containing
      protein 1 missense mutation c. 6115C>T. To our knowledge, this is the largest
      Sotos family reported. The observed phenotype is extremely variable, thus
      highlighting the clinical heterogeneity that may occur.

PMID- 21738023
TI  - Milnacipran dose-effect study in patients with burning mouth syndrome.
AB  - OBJECTIVE: The object of this study was to evaluate the dose-dependent efficacy
      and tolerability of milnacipran in patients with burning mouth syndrome (BMS)
      with inadequate response at low doses. METHODS: A 12-week open-label dose
      escalation study was conducted in 56 female patients (aged 20-83 years, with a
      mean age of 60.8 years). The initial dosage of milnacipran was 30 mg/d, and the
      dosage was raised up to 60 mg and 90 mg/d every 4 weeks until an improvement of
      at least 50% reduction of visual analog scale was achieved. RESULTS: The mean +/-
      SD effective daily dose of milnacipran was 63.9 +/-16.7 mg. The cumulative
      improvement rate for the daily dose of 30 mg was 28.6%, and this rate rose (50.8%
      67.9%) as the daily dose was increased (from 60 to 90 mg, respectively). The
      cumulative proportion of responders was significantly greater, with maximal daily
      doses of 60 and 90 mg, compared with that of 30 mg (P < 0.05, chi test). Most
      adverse events appeared at the low dose, and there was little evidence for dose
      dependence of adverse effects. No serious safety issues were observed.
      CONCLUSION: From the result of this study, dose escalation of milnacipran for
      patients with burning mouth syndrome with inadequate response at low doses may be
      helpful if the 30-mg daily dose has been tolerated well.

PMID- 21738024
TI  - Impulse control disorders associated with dopaminergic medication in patients
      with pituitary adenomas.
AB  - OBJECTIVE: Impulse control disorders (ICDs) such as pathological gambling,
      compulsive shopping, compulsive eating, and hypersexuality are a matter of
      growing interest, especially in patients with Parkinson disease who are on
      dopamine replacement therapy. It was recently reported that ICDs are associated
      with other disorders also treated with dopaminergic drugs (dopamine agonists)
      such as restless legs syndrome, multiple system atrophy, progressive supranuclear
      palsy, and fibromyalgia. The aim of this study was to determine the prevalence of
      ICDs in patients with pituitary adenomas who take dopamine agonists (DAs).
      METHODS: Twenty consecutive patients with pituitary adenomas (mostly
      prolactinomas) taking DAs were assessed. All participated in a structured
      interview focused on ICDs, which was conducted by a physician. RESULTS: Two (10%)
      of 20 subjects had a condition diagnosed as ICD. The first patient is a 35-year
      old man with giant macroprolactinoma who was alternately treated with different
      types of DAs (cabergoline, bromocriptine, and quinagolide). He developed
      compulsive eating and pathological gambling. The second patient is a 53-year-old
      man with macroprolactinoma who suffered from severe hypersexuality after
      cabergoline was begun. CONCLUSIONS: This study demonstrates the importance of
      systematic screening for ICDs in patients taking dopaminergic medication
      regardless of their primary condition.

PMID- 21738025
TI  - Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized
      clinical trial.
AB  - BACKGROUND: Topiramate is an antiepileptic drug that has been approved for
      migraine prophylaxis. Despite appropriate efficacy for migraine prophylaxis, some
      patients cannot tolerate its adverse effects. The aim of this study was to
      compare the efficacy of zonisamide, another antiepileptic drug, with topiramate
      in decreasing the frequency and severity of migraine attacks to determine whether
      it could be used as an alternative for noncompliant patients to topiramate.
      METHODS: Eighty patients, recruited from referred migraineurs to our neurology
      clinic, who met the diagnosis and inclusion criteria were allocated randomly to
      group A (50-mg/d zonisamide, gradually titrated up to 200 mg/d) and group B (25
      mg/d topiramate, gradually titrated up to 100 mg/d). Each patient was followed
      for 12 weeks and was assessed at entrance, in the fourth week and twelfth week
      for frequency of attacks, headache severity, need for acute medication, migraine
      disability assessment score, and adverse effects. A P < 0.05 was considered as
      the level of significant difference in all tests. RESULTS: Both drugs caused a
      significant decrease in frequency, severity, need for acute medication in
      migraine attacks, and migraine disability assessment score (P < 0.05). Except
      headache severity that was reduced significantly better by zonisamide (P <
      0.008), there were no significant difference between the 2 groups in other items.
      Except for 2 cases of intolerable paresthesia, both drugs were tolerated well
      during the study. CONCLUSION: Our results indicated that zonisamide is as
      effective as topiramate in migraine prophylaxis and can be considered as an
      alternative treatment when topiramate is not tolerated well.

PMID- 21738026
TI  - The dubious effect of milnacipran for the treatment of burning mouth syndrome.
AB  - OBJECTIVE: Burning mouth syndrome (BMS) is a condition accompanied by oral
      burning symptoms, including glossal pain (glossodynia) without a detectable
      cause. Although BMS is a chronic-pain syndrome, only one self-controlled pilot
      study and some case reports have reported that milnacipran is effective for the
      treatment of chronic pain, including that caused by BMS. However, these papers
      assessed only pain, and the dosage of prescribed milnacipran varied from 30 to
      150 mg/d in each patient. In this study, the dosage of prescribed milnacipran was
      set at 60 mg/d for 12 weeks for all patients, and depression and quality of life
      (QOL) were assessed in addition to pain. METHODS: Twelve patients with
      glossodynia participated in this study. Milnacipran was initiated at a dosage of
      15 mg/d and then raised gradually to 60 mg/d after 4 weeks of treatment; this
      dose was continued until the end of the study (total of 12 weeks). The evaluation
      included the Hamilton Rating Scale for Depression, the Visual Analog Scale score
      for pain evaluation, the General Oral Health Assessment Index for oral-related
      QOL evaluation, and the Medical Outcomes Study's 36-Item Short-Form Health Survey
      (SF-36) for whole QOL evaluation. RESULTS: The Hamilton Rating Scale for
      Depression score decreased significantly after treatment with a 60-mg/d dosage of
      milnacipran for 12 weeks. However, the Visual Analog Scale pain, General Oral
      Health Assessment Index, and SF-36 scores did not change. CONCLUSIONS: A
      randomized, double-blind, placebo-controlled multi-institution trial of
      milnacipran will be essential to determine its effectiveness for the treatment of
      BMS.

PMID- 21738027
TI  - When does it end? Attention-deficit/hyperactivity disorder in the middle aged and
      older populations.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is estimated to
      affect 4% to 6% of the adult population. In recent years, more and more middle
      aged and older adults (>55 years) turn to the ADHD unit at Geha Mental Health
      Center suspecting ADHD. Yet, a literature search resulted in very few relevant
      studies. METHODS AND RESULTS: This study, approved by the Geha Mental Health
      Center ethics committee, presents 11 patients, 55 years or older, diagnosed and
      treated by the unit. The patients underwent complete clinical evaluation for ADHD
      according to Diagnostic and Statistical Manual of Mental Disorder, Fourth
      Edition. The data-collection phase included demographic and clinical data; Test
      of Variables of Attention scores used as indicators of methylphenidate (MPH)
      response; Clinical Global Impression scores of both severity and improvement were
      used. Because the sample is very small, allowing only limited statistical
      analyses, nonparametric statistics were used. Eleven patients, aged 61.64 +/-
      3.87 years (male-female ratio, 9:2), were assessed. The follow-up was conducted
      for more than 2 months. Fifty-five percent had ADHD, predominantly inattentive,
      and 45% had ADHD combined type. All patients indicated suffering (Clinical Global
      Impression-Severity score range: mild = 27.3%, moderate = 45.4%, severe = 27.3%).
      Fifty-four percent showed at least 1 psychiatric comorbidity. Test of Variables
      of Attention scores showed significant improvement in 90% (8/9 patients) with MPH
      dosages similar to those used in younger adults. All patients attended the follow
      up visits. Ninety-one percent (10/11) continued with the medication. Clinical
      Global Impression-Improvement scores showed significant improvement in 73%. No
      adverse effects were reported. CONCLUSIONS: This pilot study described 11 adults
      55 years or older, diagnosed with ADHD for the first time. Attention
      deficit/hyperactivity disorder characteristics seemed to persevere; middle aged
      or older ADHD patients had similar clinical-demographic characteristics and a
      similar response to MPH as younger adults. No significant adverse effects were
      noted.

PMID- 21738028
TI  - Neonatal and adult megakaryopoiesis.
AB  - PURPOSE OF REVIEW: It has become increasingly clear that there are substantial
      biological differences between fetal/neonatal and adult megakaryopoiesis. Over
      the last 18 months, studies challenged the paradigm that neonatal megakaryocytes
      are immature and revealed a developmentally unique uncoupling of proliferation,
      polyploidization, and cytoplasmic maturation. Several studies also described
      substantial molecular differences between fetal/neonatal and adult megakaryocytes
      involving transcription factors, signaling pathways, cytokine receptors, and
      microRNAs. RECENT FINDINGS: This review will summarize our current knowledge on
      the developmental differences between fetal/neonatal and adult megakaryocytes,
      and recent advances in the underlying molecular mechanisms, including differences
      in transcription factors, in the response to thrombopoietin (Tpo), and newly
      described developmentally regulated signaling pathways. We will also discuss the
      implications of these findings on the way megakaryocytes interact with the
      environment, the response of neonates to thrombocytopenia, and the pathogenesis
      of Down syndrome-transient myeloproliferative disorder (TMD) and Down syndrome
      acute megakaryoblastic leukemia (DS-AMKL). SUMMARY: A better characterization of
      the molecular differences between fetal/neonatal and adult megakaryocytes is
      critical to elucidating the pathogenesis of a group of disorders that selectively
      affect fetal/neonatal megakaryocyte progenitors, including the thrombocytopenia
      absent radius (TAR) syndrome, Down syndrome-TMD or Down syndrome-AMKL, and the
      delayed platelet engraftment following cord blood transplantation.

PMID- 21738029
TI  - Novel aspects of factor XIII deficiency.
AB  - PURPOSE OF REVIEW: Here we review recent developments concerning the diagnosis,
      classification and treatment of factor XIII (FXIII) deficiency and new findings
      related to the pathogenesis of the disease. RECENT FINDINGS: Most recently, the
      International Society on Thrombosis and Haemostasis, Scientific and
      Standardization Committee published a guideline for the diagnosis and
      classification of FXIII deficiencies. Since 2009, three novel mutations causing
      severe bleeding diathesis were discovered in the FXIII-A gene and one in the
      FXIII-B gene. A newly described FXIII-A deficiency was of the extremely rare
      qualitative type II deficiency. The first well established founder effect was
      reported for a causative FXIII-A mutation. More than a quarter of all FXIII-A
      deficiencies are due to autoantibody, among them the first case of deficiency
      caused by anti-FXIII-B autoantibody was reported in the last 2 years. The safety
      and effectiveness of plasma FXIII concentrate for prophylaxis and treatment is
      now well established. The new recombinant FXIII product is currently in phase III
      clinical trial and the preliminary data are promising. SUMMARY: FXIII deficiency
      is considered the most underdiagnosed bleeding diathesis. The recommended
      algorithm for its diagnosis and classification could improve the diagnostic
      efficiency. The preferred choice for substitution therapy is FXIII concentrate
      (plasma-derived or, in the future, recombinant).

PMID- 21738030
TI  - The role of incretins in salt-sensitive hypertension: the potential use of
      dipeptidyl peptidase-IV inhibitors.
AB  - PURPOSE OF REVIEW: Incretin mimetics, such as glucagon-like peptide-1 (GLP-1) and
      glucose-dependent insulinotropic polypeptide (GIP), as well as dipeptidyl
      peptidase-IV (DPP-IV) inhibitors, are used in the treatment of type 2 diabetes
      mellitus (T2DM). In addition to stimulating insulin secretion from pancreatic
      beta cells, incretins have apparent extrapancreatic functions beyond glycemic
      control. This review summarizes the recent findings regarding the blood-pressure
      lowering effects of incretins and DPP-IV inhibitors in patients who are obese,
      diabetic, or have metabolic syndrome. RECENT FINDINGS: Clinical studies have
      indicated that GLP-1 and its analogues lower blood pressure in patients with
      T2DM, particularly in patients with moderate-to-severe hypertension. DPP-IV
      inhibitors also appear to elicit a similar blood-pressure-lowering effect. In
      animal models of salt-sensitive hypertension, incretins appear to induce their
      antihypertensive effects by inhibiting the proximal tubular sodium reabsorption,
      and thereby increasing urinary excretion of sodium. These data suggest that the
      local actions of incretins may be via their key role in regulating natriuresis
      and lowering blood pressure. SUMMARY: Incretin mimetics and DPP-IV inhibitors are
      a novel class of antihypertensive drugs with natriuretic properties. They can be
      used in the treatment of salt-sensitive hypertension, which is characterized by
      edema.

PMID- 21738031
TI  - Vascular compliance in blood pressure.
AB  - PURPOSE OF REVIEW: Vascular stiffening is a hallmark of the aging process.
      Improvements in the methods used to measure central stiffness, particularly
      applanation tonometry, and their use as therapeutic targets have generated great
      interest. RECENT FINDINGS: Vascular stiffness is associated with increases in
      pulse pressure (PP), aortic augmentation index, and pulse wave velocity (PWV).
      This last has emerged as the gold standard for evaluation of vascular stiffness,
      as it is an independent predictor of coronary heart disease, stroke, and
      mortality. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor
      blockers (ARBs), and calcium-channel blockers with or without diuretics are all
      commonly used to ameliorate vascular stiffness; however, selective beta-1
      blockers (beta-blockers) may actually worsen aortic PP and aortic augmentation
      index. SUMMARY: Serial measurements of vascular stiffness, including PWV,
      augmentation index, and PP, may be especially beneficial in older patients to
      supplement brachial blood pressure. At present, given the lack of universally
      accepted normal values for vascular stiffness as measured by applanation
      tonometry, serial measurements over time may be more helpful than a single
      isolated value. In patients with suspected vascular stiffening, therapy should
      include inhibition of the renin-angiotensin-aldosterone system with ACE
      inhibitors or ARBs, calcium-channel blockers, and diuretics as needed to
      normalize blood pressure. beta-Blockers should be reserved for patients with a
      history of myocardial infarction or congestive heart disease. It remains to be
      established whether beta-blockers with vasodilator properties could improve the
      assessment of vascular compliance.

PMID- 21738032
TI  - Erythropoiesis-stimulating agents, hypertension and left ventricular hypertrophy
      in the chronic kidney disease patient.
AB  - PURPOSE OF REVIEW: Left-ventricular hypertrophy (LVH) represents an important
      marker of cardiovascular morbidity and mortality. Numerous noninterventional
      studies in patients with chronic kidney disease (CKD) revealed a consistent
      relationship of LVH with modifiable risk factors attributable to failing renal
      function, particularly anemia and hypertension. RECENT FINDINGS: Given the clear
      role for anemia in initiating or accelerating LVH, it seems imperative to correct
      renal anemia with erythropoiesis-stimulating agents (ESAs). A few nonrandomized
      studies have described a regression of LVH with correction of anemia, but
      prospective randomized trials showed no evidence that ESA treatment is able to
      improve cardiac prognosis in the CKD patient. Current data alert physicians that
      normalization of hemoglobin in patients with advanced CKD is harmful. Recent
      studies are now trying to clarify the mechanisms for harm focussing on the
      influence of comorbidities, ESA doses, and hemoglobin variability. The
      pathogenesis of hypertension in CKD is multifactorial and only a small percentage
      of CKD patients have controlled their blood pressure, indicating poor medication
      adherence, insufficient control of volume overload and undertreatment. SUMMARY:
      This review provides an update of ESA treatment, hypertension and LVH in the CKD
      patient, indicating that pathogenesis of LVH in this population is currently not
      completely understood. In addition, the impact of pharmacological interventions
      targeted to prevent or reduce LVH in anemic or hypertensive CKD patients is not
      well defined. As adoption of the Framingham approach seems not feasible in the
      CKD patient, evidence from large-scale randomized clinical trials is mandatory to
      resolve this dilemma.

PMID- 21738033
TI  - Treatment of juvenile idiopathic arthritis-associated uveitis: challenges and
      update.
AB  - PURPOSE OF REVIEW: To update the current understanding of the risk factors for
      poor outcomes in juvenile idiopathic arthritis-related uveitis. In addition,
      current therapies, both traditional and biological, are reviewed. RECENT
      FINDINGS: Male sex, independent of age or antinuclear antibody status, is
      associated with increased ocular morbidity. Having anterior chamber inflammation
      on first exam increases the risk of developing vision-threatening eye
      complications. Presence of one complication increases the risk of developing
      another. Risk of cataract development associated with topical glucocorticoid use
      is better defined. Longer duration of remission on therapy has been found to
      decrease the risk of disease flare after discontinuation of methotrexate. Recent
      studies of both nonbiological and biological therapies for arthritis-related
      uveitis are discussed. SUMMARY: With a better understanding of risk factors
      associated with the ocular morbidity of uveitis associated with juvenile
      idiopathic arthritis, aggressive therapies can be targeted for improved visual
      outcomes. Alternative treatments to avoid long-term corticosteroid use include
      the use of antimetabolites and biological therapies. More prospective comparator
      studies and/or use of multicenter databases are needed to better understand best
      treatments.

PMID- 21738034
TI  - Spiritual needs assessments and measurements.
AB  - PURPOSE OF REVIEW: This review discusses the developments in spiritual needs
      assessments and measurements in end-of-life care. The review considers spiritual
      needs assessments from the perspective of palliative care patients, their
      families and caregivers, and healthcare professionals. RECENT FINDINGS: Spiritual
      needs assessments vary significantly along the dimensions of content and domains.
      These needs assessments have the potential to deepen our insight and to identify
      those who are most at risk for spiritual distress, but few are practical and
      simple enough to use in everyday clinical practice, and for the research, few are
      cross-culturally validated. Spirituality is a complex construct, although
      'relatedness' was recognized as a core dimension of spirituality in addition to
      existential beliefs and values related to meaning and purpose. Little is known
      about the spiritual needs in elderly patients, in the cognitively impaired, and
      during the dying process. The spiritual needs of family caregivers need more
      support and attention. SUMMARY: Spirituality is considered to be one of the
      patient's vital signs and should be routinely screened and assessed. Research in
      spiritual care should be ongoing for all palliative care patients as well as for
      those with specific needs such as mental, neurological, or cognitive impairment.
      There is also a knowledge gap concerning how spiritual needs change during the
      progression of the disease trajectory. More work must be done on the spiritual
      concerns of family caregivers.

PMID- 21738035
TI  - Variation in attitudes towards artificial hydration at the end of life: a
      systematic literature review.
AB  - PURPOSE OF REVIEW: Artificial hydration in end-of-life care is an important and
      emotive topic that frequently raises concerns from patients, relatives and
      healthcare professionals (HCPs). The aim of this review was to give an overview
      of currently available evidence around opinions and attitudes towards artificial
      hydration at the end of life. RECENT FINDING: In total 11 studies reported on
      opinions towards providing artificial hydration, nine studies reported on
      attitudes towards the effect of artificial hydration on quality-of-life and four
      studies towards its effect on survival. Reported percentages of respondents in
      favour of providing artificial hydration at the end of life varied from 22 to
      100% and for nonprovision from 0 to 75%. One-third of the general public has been
      found to think that artificial hydration improves comfort, while among patients a
      majority feels it can have a physical or psychological benefit. HCPs were found
      to be less optimistic: 1-43% thought patients benefit from artificial hydration
      at the end of life. HCPs mostly agree artificial hydration does not prolong
      survival, although up to 89% of patients expect it does. SUMMARY: Opinions and
      attitudes towards the use of artificial hydration at the end of life vary.
      Communication of this imperative topic in end-of-life care is important for
      better care and should be research-based.

PMID- 21738036
TI  - Familial bladder cancer and the related genes.
AB  - PURPOSE OF REVIEW: Family history of bladder cancer is a known risk factor for
      bladder cancer but new data have emerged on the influence of a family history of
      other tumours than bladder cancer. Recent data have shown that family history
      influences survival of bladder cancer. Gene identification has been successful
      particularly on low-risk genes influencing susceptibility and prognosis. RECENT
      FINDINGS: Familial clustering of bladder cancer has been found with cancers of
      the stomach, larynx, kidney, endometrium and the bone marrow (leukaemia). Shared
      smoking habits are an explanation to these findings and between spouses these
      appear to be the only explanation to the clustering of cancers with bladder
      cancer. Family members also share prognosis of bladder cancer, either good or
      poor survival. Among the low-penetrant genes, the variants within the genes
      encoding metabolic enzymes have been consistently associated with susceptibility
      to bladder cancer and the evidence is compelling for NAT2 slow acetylator and
      GSTM1 null genotypes. SUMMARY: Smoking is the only identifiable environmental
      factor explaining familial clustering of bladder cancers and other cancers.
      Genetic factors are likely to contribute to many of the described associations
      but the identified genes are probably an introduction to the genetics of bladder
      cancer.

PMID- 21738037
TI  - Which patients benefit the most from neoadjuvant chemotherapy in advanced bladder
      cancer?
AB  - PURPOSE OF REVIEW: Despite 5% advantage in 5-year overall survival, neoadjuvant
      chemotherapy may result in considerable overtreatment of bladder cancer patients
      because of the lack of response criteria. The review's purpose was to identify
      the criteria on which the selection of bladder cancer patients for neoadjuvant
      chemotherapy followed by radical cystectomy should be based. RECENT FINDINGS:
      About 30-40% of patients with metastatic bladder cancer are ineligible for
      platinum-based neoadjuvant chemotherapy because of renal impairment.
      Stratification based on the clinical tumor stage is likely to be biased by
      inappropriate preoperative staging. Differences in the response to neoadjuvant
      chemotherapy seem not to be predictable by histological subtype of bladder
      cancer. Future developments in radiological imaging, molecular cancer staging and
      response prediction aim to identify patients who will profit from neoadjuvant
      chemotherapy. SUMMARY: Patients considered for neoadjuvant chemotherapy should be
      eligible for cisplatinum-based regimens. To avoid overtreatment, preferably
      patients with nonorgan-confined and lymph-node disease should be treated by
      neoadjuvant chemotherapy. However, the possibility of staging error should be
      taken into account. Patients with limited metastatic disease may also profit from
      neoadjuvant chemotherapy followed by radical cystectomy with concomitant
      metastasectomy.

PMID- 21738038
TI  - Feasibility of a modified outpatient regimen of intravenous/intraperitoneal
      chemotherapy in optimally debulked stage III ovarian cancer patients: a GEICO
      study.
AB  - OBJECTIVES: The objective of the study was to assess the feasibility, toxicity,
      and reasons for early discontinuation of a modified outpatient
      intraperitoneal/intravenous (IP/IV) chemotherapy regimen for the treatment of
      patients with optimally debulked stage III ovarian cancer. METHODS: Between
      February 2006 and November 2008, 51 consecutive patients from Institutions of the
      Spanish Ovarian Cancer Group (GEICO) were treated with a modified outpatient IP
      chemotherapy regimen. Patients received IV paclitaxel 175 mg/m over 3 hours on
      day 1, followed by IP cisplatin 100 mg/m (or 75 mg/m according to the principal
      investigator's criteria) on day 2. On day 8, patients received IP paclitaxel 60
      mg/m. To homogenize the IP administration and supportive measures, a GEICO
      guideline for IP chemotherapy was established. Patients were treated with the
      intention to receive 6 courses of chemotherapy every 21 days. RESULTS: The median
      age of the patients was 49 years (range, 36-75 years), and most of them had
      papillary serous ovarian cancer (78%), International Federation of Gynecology and
      Obstetrics stage IIIC (76%). Thirty-nine patients completed 4 or more IP cycles,
      and 28 (61%) completed all 6 IP cycles. Twenty-two patients discontinued the
      IP/IV treatment, mainly because of chemotherapy toxicity (10 patients) and
      catheter-related complications (5 patients). The most prevalent grade 3/4
      toxicities were neutropenia (14 patients; 30%) and gastrointestinal events (12
      patients; 26%). CONCLUSIONS: The GEICO outpatient modified regimen resulted in a
      lesser toxicity and a greater rate of treatment completion than previously
      reported. The accurate selection of patients and the administration following
      well-defined guidelines can increase the feasibility of IP chemotherapy
      administration.

PMID- 21738039
TI  - Prognostic impact of prechemotherapy serum levels of HER2, CA125, and HE4 in
      ovarian cancer patients.
AB  - OBJECTIVE: Human epididymis protein 4 (HE4) has attracted a lot of interest as a
      relatively novel biomarker for ovarian carcinoma. Research focus has been
      directed at HE4 as a diagnostic tool with potential for better triage of women
      with adnexal masses but the prognostic aspect of HE4 in ovarian cancer patients
      remains to be elucidated. The aim of the present study was to investigate the
      prognostic value of prechemotherapy serum HER2, cancer antigen 125 (CA125), and
      HE4 levels in ovarian cancer patients receiving standard combination
      chemotherapy. METHODS: Serum from 139 patients with newly diagnosed ovarian
      cancer was analyzed for HER2, CA125, and HE4 using enzyme-linked immunosorbent
      assay assays. Samples were collected just before first-line chemotherapy, and all
      patients were treated with carboplatin-paclitaxel combination chemotherapy.
      RESULTS: Increasing levels of serum HE4 (grouped into quartiles) was
      significantly associated with worse progression-free survival (PFS) (P < 10) and
      overall survival (P < 10). After adjustment in the Cox model, HE4 serum levels
      remained an independent prognostic parameter for PFS, with a hazard ratio of 1.77
      (95% confidence interval, 1.03-3.04; P = 0.040) for patients with HE4 levels
      above the median compared with patients with HE4 levels below the median. The
      shorter PFS for patients with high levels of HE4 also translated into an
      independent significant difference in overall survival (hazard ratio, 3.17 [95%
      confidence interval, 1.41-7.10]; P = 0.005).Serum HER2 and CA125 levels did not
      demonstrate an independent prognostic value. CONCLUSIONS: High levels of serum
      HE4 is a strong and independent indicator of worse prognosis in epithelial
      ovarian cancer patients.

PMID- 21738040
TI  - Comparison of the efficacy and toxicity between radiotherapy and chemotherapy in
      nodal and isolated nonnodal recurrence of ovarian cancer.
AB  - OBJECTIVES: To assess and compare the efficacy and toxicity of radiotherapy (RT)
      versus chemotherapy (CT) in patients with nodal and isolated nonnodal recurrence
      of ovarian cancer. METHODS: Records of 67 patients treated for nodal or isolated
      nonnodal ovarian cancer recurrence (50 treated with RT and 17 treated with CT)
      between 2001 and 2010 were retrospectively reviewed. Patients' responses to RT
      and CT were assessed by the Response Evaluation Criteria in Solid Tumors, and
      toxicity was evaluated according to the National Cancer Institute Common Toxicity
      Criteria, version 3.0. Progression-free survival and overall survival were
      calculated using the Kaplan-Meier method. RESULTS: The overall response rate was
      64.0% in the RT group and 16.7% in the CT group (P = 0.003). The median follow-up
      time was 38 months (range, 3-97 months) for RT and 18 months (range, 70-64
      months) for CT. The median progression-free survival was 6 months for
      radiotherapy and 5 months for chemotherapy (P = 0.212). Median overall survival
      between the 2 groups was not significantly different (P = 0.246). There was no RT
      mediated grade 3 or 4 hematologic toxicity, but overall toxicity was not
      significantly different between the 2 groups. CONCLUSIONS: Radiotherapy resulted
      in a better response and tolerable toxicities compared to CT in patients with
      either nodal or isolated nonnodal ovarian cancer recurrence. However, progression
      free survival and overall survival did not differ between RT and CT. A
      prospective, multicenter, randomized controlled study is needed to evaluate the
      survival benefits of RT for ovarian cancer.

PMID- 21738041
TI  - The preparation of human papillomavirus type 58 vaccine and exploring its
      biological activity and immunogenicity in vitro.
AB  - OBJECTIVES: Human papillomavirus (HPV) type 58 is the second most prevalent virus
      infection among Chinese women. To develop an HPV58 vaccine that combines both
      prophylactic and therapeutic functions, we generate a chimeric virus-like
      particle (cVLP). METHODS: The cVLPs contain both whole length L1 and parts of E7
      peptides either from E7 amino acids (aa) 50 to aa72 or from E7 aa4 to aa12. The
      HPV58 L1-E7aa50-72 and L1-E7aa4-12 fusion proteins were revealed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and confirmed by Western blot
      (Supplementary Digital Content 1, http://links.lww.com/IGC/A40, which shows
      alignment of the protein sequence between HPV58 L1-E7aa50-72/4-12 and standard
      sequence). Protein folding and location of cVLPs were identified by transmission
      electron microscope. The immunogenicity of the fusion protein was tested by
      enzyme-linked immunospot assay. RESULTS: Transmission electron microscope showed
      that the fusion protein formed cVLPs by self-assembly and the majority of
      particles located in the nucleus of the sf-9 insect cells. The cVLPs displayed a
      strong ability to agglutinate erythrocytes, which is distinguished from the
      parental VLPs. In addition, the purified HPV58 L1-E7aa50-72 or L1-E7aa4-12 fusion
      protein induced significant numbers of interferon gamma-expressing E7aa50-72- or
      E7aa4-12-specific CD8 T cells. DISCUSSION: Our results indicate that the
      insertion of the E7aa50-72 or E7aa4-12 peptides behind L1 did not disrupt the
      assembly of cVLPs and provided potent immunogenicity and bioactivity, which
      created a powerful basis for further preparations of HPV58 vaccines with
      prophylactic and therapeutic effects for the treatment of HPV58-related diseases
      including cervical cancer.

PMID- 21738042
TI  - Trends and patterns of ovarian cancer mortality in Belgrade, Serbia: a joinpoint
      regression analysis.
AB  - OBJECTIVE: Ovarian cancer (OC) represents the leading cause of gynecological
      cancer deaths. The aim of our study was to estimate the patterns and trends in OC
      mortality in the population of Belgrade (Serbia) during the period 1976 to 2007.
      METHODS: Mortality data (official death certificates) for OC have been gathered
      from the Municipal Institute of Statistics in Belgrade. Mortality rates with
      corresponding 95% confidence intervals were adjusted by the European standard
      population. Trends in age-adjusted and age-specific mortality rates were
      calculated using joinpoint regression, according to the method of Kim et al. An
      annual percent of changes in mortality rates for each line segment was estimated
      by fitting a regression line to the natural logarithm of the rates using calendar
      years as a regressor variable. RESULTS: The average age-adjusted OC mortality
      rate during the period 1976-2007 was 5.4/100,000 (95% confidence interval, 4.8
      6.1). For total women population, no joinpoint is found, whereas significantly
      increasing mortality trend was observed during the whole study period (+3.6%
      annually; P < 0.001). In the group age 55 to 64 years, one joinpoint was detected
      with a significant increase in OC mortality trend between 1976 and 1990 (+9.8%
      annually; P < 0.001) and with nonsignificant decreasing tendency between 1990 and
      2007 (-1.0% annually; P = 0.773). In the two oldest age groups, statistically
      significantly increasing tendency in OC mortality was evident during the overall
      calendar period with no apparent change in linear trends. CONCLUSIONS: Mortality
      due to the OC in Belgrade has continued to increase, suggesting that this
      malignancy is becoming an increasing public health problem in our country.

PMID- 21738043
TI  - Analysis of clinicopathologic prognostic factors in 9 patients with epithelioid
      trophoblastic tumor.
AB  - OBJECTIVE: This study aimed to investigate the clinicopathologic features and
      prognostic factor in patients with epithelioid trophoblastic tumor (ETT).
      METHODS: From January 2002 to June 2010, the clinicopathologic characteristics,
      treatments, outcomes, and prognosis of 9 patients with ETT were analyzed
      retrospectively in our institution. RESULTS: Of 9 patients, 8 (88.9%) had
      metastases. The histopathologic results of 7 patients (77.8%) with poor outcomes
      showed diffuse multifocal disease within the uterus, full-thickness myometrial
      invasion, uterine serosal involvement, and extensive necrosis. The size of the
      uterus exceeded 8 weeks of gestation in 7 patients. Two of them had poorly
      differentiated carcinoma. All patients were treated with multimodality treatment
      that combined with surgery and chemotherapy. After the initial treatments, 5
      patients with International Federation of Gynecology and Obstetrics stage I
      achieved complete remission (CR), 1 patient achieved partial remission, and 3
      patients (33.3%) had no response to treatments and died of progressive disease.
      After following up for 6 to 107 months (mean, 24 months), 4 (44.4%) of the 5
      patients with initial CR had relapse: 3 of them achieved a second CR and the
      other 1 was under treatment. CONCLUSIONS: Epithelioid trophoblastic tumor is a
      rare and special type of intermediate trophoblastic tumor with a high degree of
      malignancy and poor prognosis. Multifocal lesions in bulky uterus, combined with
      full-thickness myometrial invasion and uterine serosal involvement, could be
      related to poor outcomes in patients with ETT. The prognosis of ETT could be
      improved by increasing diagnostic accuracy, identifying prognostic factor at an
      early stage, and providing early intensive multimodality treatment to patients
      with poor prognostic factors.

PMID- 21738044
TI  - Silencing of CXCR4 blocks progression of ovarian cancer and depresses canonical
      Wnt signaling pathway.
AB  - OBJECTIVE: CXC chemokine receptor 4 (CXCR4) was considered to be an important
      factor in cancer cell metastasis. This study was aimed to examine the expression
      of CXCR4 in ovarian cancer and determine the functions and the possible
      mechanisms of CXCR4 in the progression of ovarian cancer. METHODS: CXC chemokine
      receptor 4 messenger RNA expression in normal ovarian tissues, malignant
      epithelial ovarian tumors, and 3 ovarian cancer cell lines was analyzed.
      Immunohistochemical analysis was used to detect the protein expression of CXCR4
      and beta-catenin in normal and malignant ovarian tissues. The effect of CXCR4
      inhibition on cell proliferation and invasion was determined. RESULTS: CXC
      chemokine receptor 4 was highly expressed in malignant ovarian tumors and ovarian
      cancer cell lines, and the different expression of CXCR4 was observed between the
      ovarian cancers with lymph node metastasis and without lymph node metastasis.
      Furthermore, The CXCR4 expression was correlated with beta-catenin expression in
      ovarian tissues. Moreover, knockdown of CXCR4 could obviously reduce
      proliferation and invasion of ovarian cancer cell and inhibit Wnt target genes
      and mesenchymal markers such as vimentin and SLUG expression. CONCLUSIONS: CXC
      chemokine receptor 4 plays a critical role in the metastasis of human ovarian
      cancer possibly through modulating the Wnt/beta-catenin pathway. CXC chemokine
      receptor 4 is a potential therapeutic target for treatment of ovarian cancer.

PMID- 21738045
TI  - Hydronephrosis as a prognostic indicator of survival in advanced cervix cancer.
AB  - OBJECTIVE: To determine whether hydronephrosis is an independent prognostic
      indicator of survival among patients with advanced cervical carcinoma. Moreover,
      we wanted to demonstrate the relationship between unilateral and bilateral
      hydronephrosis and overall survival. METHODS: Retrospective analysis of 197
      patients with International Federation of Gynecology and Obstetrics (FIGO) stage
      IIIB cervical carcinoma or higher treated between 1990 and 2007 was conducted.
      Inclusion criteria were clinical staging according to FIGO criteria, standardized
      radiation treatment and cisplatin-based chemosensitization regimens. Associations
      between hydronephrosis and covariates-age, race, histopathologic diagnosis,
      pelvic sidewall involvement, stage, nodal involvement, and Gynecologic Oncology
      Group/Eastern Cooperative Oncology Group performance status (PS)-were determined.
      Statistical analysis including Kaplan-Meier, log-rank test, proportional hazards
      regression, Fisher exact test, and Mann-Whitney test were used where appropriate,
      with P < 0.05 considered significant. RESULTS: Of 143 included patients, 73
      patients had no hydronephrosis (HN), 39 patients had unilateral HN, and 31
      patients had bilateral HN. Twenty-nine patients (40%) with no HN died compared to
      24 patients (61.5%) with unilateral HN and 21 patients (67.7%) with bilateral HN.
      Median time to death was significantly shorter for patients with unilateral HN
      (27 months; 95% confidence interval [CI], 10-48) and bilateral HN (12 months; 95%
      CI, 6-23) versus patients without HN (68 months; 95% CI, 39-infinity; P < 0.001).
      Unadjusted hazard ratio (HR) for HN (both unilateral and bilateral) was 2.4 (95%
      CI, 1.5-3.8); P < 0.001. Of potential covariates evaluated, PS and sidewall
      involvement were significantly associated with HN (P = 0.021 and P = 0.014,
      respectively). Proportional hazards regression revealed that controlling for use
      of radiation, chemotherapy, and for PS, HN was still significantly associated
      with poor prognosis (HR unilateral HN = 2.0, 95% CI, 1.2-3.5; HR bilateral HN =
      3.2, 95% CI, 1.7-6.0); P <= 0.001. CONCLUSION: Hydronephrosis is an independent
      poor prognostic indicator of survival in patients with advanced cervical cancer.
      Bilateral hydronephrosis compared to unilateral involvement confers a worse
      overall prognosis. Additional studies are needed to determine if FIGO staging
      should be amended.

PMID- 21738046
TI  - Return to work among employees with long-term sickness absence in eldercare: a
      prospective analysis of register-based outcomes.
AB  - This study investigates whether psychosocial work characteristics and work
      related psychological states predict return to work (RTW) after long-term
      sickness absence among eldercare staff. We followed 9947 employees in a national
      register on payment of sickness-absence compensation for 1 year and found that
      598 employees had absence periods of 8 or more consecutive weeks. Using Cox
      regression analysis, these 598 employees were followed for a year after onset of
      sickness absence to investigate associations between baseline questionnaire data
      on psychosocial work characteristics and work-related psychological states on the
      one side and 'risk' of RTW on the other. The results showed that none of the
      psychosocial work characteristics, emotional demands, role conflicts, quality of
      leadership and influence, were significantly associated with RTW. Of the two work
      related psychological states, affective organizational commitment and experience
      of meaning at work, the results showed that sickness-absent employees who
      experienced low meaning at work at baseline had a significantly reduced 'risk' of
      RTW when compared with employees who experienced high meaning at work. No
      significant associations were found for affective organizational commitment. The
      results imply that experience of meaning at work must be considered an important
      work-life resource, as it enhances the capacity of sickness-absent employees to
      RTW after extended sickness-absence periods.

PMID- 21738047
TI  - Excimer laser coronary angioplasty with manual thrombus aspiration for a case of
      very late stent thrombosis of sirolimus-eluting stent.
AB  - Very late stent thrombosis occurring after drug-eluting stent implantation is a
      rare complication. However, it is often associated with poor outcome. Manual
      thrombectomy has been shown to lower the rate of distal embolization in the case
      of ST-elevation myocardial infarction of native coronary arteries. However, the
      presence of abundant thrombus material may lead to manual thrombus aspiration
      failure. Here, we describe the case of a patient with acute myocardial infarction
      due to stent thrombosis of a sirolimus-eluting stent occurring 50 months after
      stent deployment showing abundant thrombus material, which led to manual thrombus
      aspiration failure and was then successfully treated by excimer laser coronary
      angioplasty. In these cases, excimer laser coronary angioplasty may be useful due
      to its ability to dissolve thrombus.

PMID- 21738048
TI  - Single-nucleotide polymorphisms at the adiponectin locus and risk of coronary
      artery disease in Tunisian coronaries.
AB  - OBJECTIVE: Adiponectin is an adipocyte-derived hormone and an essential modulator
      of insulin sensitivity. Several studies suggest an important role of adiponectin
      in the process leading to atherosclerosis, thus indicating the adiponectin gene
      as a potential candidate for coronary artery disease. Two single-nucleotide
      polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) have been
      associated with low circulating adiponectin levels, insulin resistance and type 2
      diabetes. The objective was to examine the association of two SNPs (45T/G and
      276G/T) with coronary artery disease in a Tunisian population. METHODS: We have
      recruited 316 Tunisian patients, documented by coronary angiography. Significant
      coronary stenosis (SCS) was defined as a luminal narrowing of at least 50% in at
      least one major coronary artery. Genotyping was performed by polymerase chain
      reaction restriction fragment length polymorphism. Lipids and apolipoproteins
      were measured. RESULTS: After adjustments for confounder parameters, odds ratio
      (OR) of SCS associated with 276G/T mutated genotypes was 0.472 [95% confidence
      interval (CI) 0.195-0.842, P=0.046]. The mutated genotypes at the +45T/G
      polymorphism were significantly associated with increased SCS only in obese
      patients (OR 3.31, 95% CI 0.996-11.05, P=0.049 versus OR 1.71, 95% CI 0.467
      6.269, P=0.418 in non-obese individuals). A potential protective effect was also
      observed for the haplogenotype TT/TT (OR 0.548, 0.306-0.982, P=0.043) in all the
      studied population. CONCLUSION: Mutated genotypes at +45T/G (GG + TG) were
      associated with an increase in SCS only in the obese group. Mutated genotypes at
      +276G/T (TT + GT) seem to reduce the risk of SCS in the studied population. When
      the two SNPs were combined, the TT/TT haplogenotype (normal genotype at 45T/G and
      mutated genotype at 276G/T) was associated with a protective effect.

PMID- 21738049
TI  - Real-world management of atrial fibrillation in Internal Medicine units:  the
      FADOI 'FALP' observational study.
AB  - BACKGROUND: Atrial fibrillation is the most frequent arrhythmia, but few data are
      available on patients' characteristics and management in the context of Internal
      Medicine wards. METHODS: Data were collected at the beginning of 2010 in 18
      Internal Medicine units of the regions Liguria and Piemonte (Italy). Each centre
      reviewed the hospital charts of the last 50 patients discharged during the year
      2009 in whom a diagnosis of atrial fibrillation had been made (patient's history
      or during the hospitalization). RESULTS: A total of 903 atrial fibrillation
      patients were evaluated. Prevalence of atrial fibrillation among patients
      hospitalized in Internal Medicine units was 18.2%. More than 85% of patients had
      at least two diseases other than atrial fibrillation, and 'lone' atrial
      fibrillation was rare (1.3%). During hospital stay, 80.5% of the patients
      received at least one treatment for atrial fibrillation: 55.5% received an
      antithrombotic and 61.8% a drug for arrhythmia, mostly aimed at rate control
      (47.2%). In-hospital all-cause mortality was 13.4%. At discharge, 70.2 and 68.9%
      of the patients received prescription of a drug for arrhythmia and for
      antithrombotic treatment, respectively. Prescription of oral anticoagulants was
      significantly associated with hypertension, while previous bleeding, age above 75
      years, paroxysmal atrial fibrillation, male sex and a number of concomitant drugs
      of more than four were strong negative predictors. CONCLUSION: Data from our
      study confirm that atrial fibrillation is a common finding in patients
      hospitalized in Internal Medicine units, and this population is characterized by
      multiple comorbidities and severe prognosis. Discrepancies exist between
      recommendations by guidelines and real-world management, owing to the complexity
      of patients and limits of existing treatment strategies.

PMID- 21738050
TI  - Patients with acute coronary syndrome and nonobstructive coronary artery disease
      in the real world are markedly undertreated.
AB  - OBJECTIVES: We assessed the clinical profile of patients with acute coronary
      syndrome (ACS) and nonobstructive coronary artery disease (CAD) in a real world
      setting, focusing on pattern of care and on prognosis. METHODS: Each
      nonobstructive CAD (<50% stenosis in any epicardial coronary artery) patient was
      matched with an obstructive CAD patient; adjusted estimates of prescription of
      guideline-recommended drugs at discharge and of long-term prognosis were
      evaluated. RESULTS: Among 2995 consecutive ACS patients who underwent coronary
      angiography, 125 (4.2%) had nonobstructive CAD. Nonobstructive CAD patients had
      significantly lower odds of receiving aspirin [odds ratio (OR) 0.31, 95%
      confidence interval (CI): 0.14-0.68], thienopyridines (OR 0.01, 95% CI: 0.00
      0.07), statins (OR 0.31, 95% CI: 0.17-0.58), beta-blockers (OR 0.32, 95% CI: 0.17
      0.63) and angiotensin converting enzyme-inhibitors /angiotensin receptor blockers
      (OR 0.36, 95% CI: 0.17-0.91) compared with matched patients. During a 3-year
      follow-up, nonobstructive CAD patients had significantly fewer cardiovascular
      deaths and myocardial infarctions but numerically more episodes of unstable
      angina. CONCLUSIONS: The prevalence of nonobstructive CAD appears lower (4.2%)
      compared with published data. After extensive adjustment, patients with
      nonobstructive CAD were significantly less likely to be treated with guideline
      recommended therapy, including aspirin and statins. Multicenter prospective
      studies targeting this specific population and the potential benefit of guideline
      recommended therapies appear warranted.

PMID- 21738051
TI  - Acute aortic dissection: a case report showing penetrating thoracic aortic ulcer
      and infrarenal aortic rupture.
AB  - An acute aortic syndrome with simultaneous presence of a penetrating aortic
      ulcer, an intramural haematoma, a thoracic aortic dissection and an abdominal
      aortic aneurysm rupture has not previously been reported. Herein, we describe our
      experience with a patient treated by endovascular means with an 8-year follow-up.

PMID- 21738052
TI  - Uromodulin gene variant is associated with type 2 diabetic nephropathy.
AB  - AIMS/HYPOTHESIS: About 35% of individuals with type 2 diabetes develop persistent
      albuminuria, lose renal function, and are at increased risk for microvascular
      complications like diabetic nephropathy. Recent genome-wide association studies
      have identified the uromodulin locus (UMOD), encoding the most common protein in
      human urine to be associated with hypertension and also with chronic kidney
      disease (CKD). In the present study we examined the association of the common
      variant of the uromodulin (UMOD) gene with type 2 diabetic nephropathy and kidney
      function. METHODS: UMOD variant rs13333226 was genotyped in a case-control
      material including 4888 unrelated type 2 diabetic individuals (n = 880 with and n
      = 4008 without nephropathy) from Sweden (Scania Diabetes Registry) using the ABI
      Real time TaqMan allelic discrimination assay. RESULTS: The G allele of
      rs13333226 was associated with a decreased risk of nephropathy [odds ratio (OR)
      0.80, 95% confidence interval (CI) 0.69-0.91, P = 0.001] after correction for
      confounding factors like age, sex, body mass index (BMI), blood pressure, kidney
      function, smoking and duration of diabetes. The same allele was also associated
      with a better kidney function [estimated glomerular filtration rate (eGFR), beta
      = 0.117, P < 0.0001] and lower systolic blood pressure (beta = -0.048, P = 0.013)
      in the overall study cohort. CONCLUSION/INTERPRETATION: The present study
      highlights that the common variant of the UMOD gene is protective against
      diabetic nephropathy susceptibility and also affects kidney function and blood
      pressure in patients with type 2 diabetes. However, the association with diabetic
      nephropathy was independent of blood pressure and kidney function.

PMID- 21738053
TI  - Clinical significance of nonalbuminuric renal impairment in type 2 diabetes.
AB  - OBJECTIVE: In type 2 diabetes, prevalence of nonalbuminuric renal impairment is
      increasing worldwide, though its clinical significance remains unclear. This
      large-cohort study aimed at evaluating the association of this phenotype with
      cardiovascular risk factors and other complications. METHODS: Type 2 diabetic
      patients from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian
      Multicenter Study (n = 15,773), visiting consecutively 19 hospital-based Diabetes
      Clinics in years 2007-2008, were examined. Serum creatinine was assessed by the
      Jaffe method; albuminuria was measured by immunonephelometry or
      immunoturbidimetry. RESULTS: Of patients with renal impairment, as identified by
      an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2,
      56.6% were normoalbuminuric, 30.8% were microalbuminuric, and 12.6% were
      macroalbuminuric. Percentages were similar when GFR was estimated using the more
      accurate Chronic Kidney Disease Epidemiology Collaboration equation instead of
      the simplified Modification of Diet in Renal Disease formula, and were
      independent of age, thus indicating that the increasing prevalence of this
      phenotype does not reflects misclassification of elderly patients. Nonalbuminuric
      renal impairment was not associated with HbA(1c) and correlated less strongly
      with retinopathy and hypertension than albuminuria, either alone or associated
      with reduced eGFR. It was associated with a higher prevalence of cardiovascular
      disease (CVD) than albuminuria alone, but lower than albuminuric renal
      impairment. Female sex correlated with nonalbuminuric renal impairment and male
      sex with the albuminuric forms. CONCLUSIONS: These data show that type 2 diabetic
      patients with nonalbuminuric renal impairment exhibit distinct clinical features,
      suggesting predominance of macroangiopathy as underlying renal pathology, and
      that this phenotype is associated with significant CVD burden.

PMID- 21738054
TI  - Primary aldosteronism: changes in cystatin C-based kidney filtration,
      proteinuria, and renal duplex indices with treatment.
AB  - OBJECTIVES: To obtain information about the effect of prolonged aldosterone
      excess on kidney function. METHODS: We determined kidney function changes defined
      by cystatin C-based estimations of glomerular filtration rate (CysC-GFR).
      Pretreatment proteinuria and intrarenal Doppler velocimetric indices in primary
      aldosteronism were examined and followed after adrenalectomy or spironolactone
      treatment. RESULTS: This prospective, multicenter study included 130 primary
      aldosteronism patients (56 men; age, 49.9 +/- 13.4 years: 100 with adenoma and 30
      with idiopathic hyperaldosteronism) and 73 essential hypertension patients (36
      men; age, 51.4 +/- 14.8 years) as controls. Patients with primary aldosteronism
      had higher CysC-GFR (P < 0.05) and heavier proteinuria (0.042) than those with
      essential hypertension. With primary aldosteronism, a higher aldosterone-renin
      ratio (odds ratio, OR = 7.85, P = 0.008) was independently related to
      pretreatment CysC-GFR. The factors related to pretreatment proteinuria included
      CysC-GFR (OR, -0.006, P = 0.001), plasma aldosterone concentration (OR, 0.004, P
      = 0.002), and duration of hypertension (OR, 0.016, P = 0.032). Duration of
      hypertension was also independently correlated with the pretreatment resistive
      index among primary aldosteronism patients (OR, 0.004, P = 0.035). CysC-GFR (all,
      P < 0.05), proteinuria (P < 0.001), and resistive index (P < 0.001) decreased 1
      year after adrenalectomy but not with spironolactone treatment. CONCLUSION: Our
      data suggest that prolonged hyperaldosteronism will cause relative kidney
      hyperfiltration and reversible intrarenal vascular structural changes, which
      disguise the consequent renal injury, including declining GFR and proteinuria.
      Adrenalectomy and spironolactone treatment exert different clinical impacts
      toward kidney damage even with a similar blood pressure-lowering effect.

PMID- 21738055
TI  - Generic switch after ramipril patent expiry is not associated with decreased
      pharmacy refill compliance: a retrospective study using the DAPI database.
AB  - OBJECTIVE: For treatment success in chronic diseases such as hypertension,
      adequate adherence to long-term pharmacotherapy is a prerequisite. The purpose of
      this study was to evaluate whether switching from brand name ramipril to a
      generic product after patent expiry may negatively affect patients' refill
      compliance. METHODS: Claims data for ambulatory prescriptions within the
      statutory health insurance system were evaluated. Patients were included if they
      had filled a ramipril prescription (index) for either brand name or generic
      ramipril products between September 2003 and June 2004. Patients had to be
      continuously treated with ramipril for at least 12 months before and after the
      index date. Patients with a change from brand name to generic product or vice
      versa during follow-up after the index date were excluded from the analyses, as
      were patients who could not be unequivocally allocated to characteristics of
      covariates. Refill compliance was analysed by calculating the medication
      possession ratio (MPR), assuming that patients were prescribed one unit dose per
      day (MPR(UD)). RESULTS: In total, 142,690 and 79,191 patients were classified as
      brand name or generic therapy, respectively. Median MPR(UD) values were 0.95 and
      0.96 (P < 0.001). In a logistic regression model adjusting for covariates, the
      probability for noncompliance (MPR(UD) < 0.8) was marginally lower in the generic
      compared with the brand name group (odds ratio 0.926, 99% confidence interval
      0.901-0.951, P < 0.001). CONCLUSION: These results suggest that refill compliance
      is not negatively affected by a physician-induced switch from brand name to
      generic ramipril products after patent expiry.

PMID- 21738056
TI  - Neuregulin-1/ErbB signaling in rostral ventrolateral medulla is involved in blood
      pressure regulation as an antihypertensive system.
AB  - OBJECTIVES: Neuregulin-1 (NRG-1), located in the central nervous system (CNS),
      plays an important role in synaptic function, neurite outgrowth, and survival of
      neurons and glia acting on the ErbB receptor family. However, the functional role
      of NRG-1/ErbB signaling in the CNS and blood pressure regulation is unknown,
      particularly in the rostral ventrolateral medulla (RVLM), a major vasomotor
      center. Thus, we investigated whether NRG-1/ErbB signaling in the RVLM is
      involved in blood pressure regulation. METHODS AND RESULTS: Microinjection of NRG
      1 into the RVLM decreased arterial blood pressure, heart rate (HR), and renal
      sympathetic nerve activity (RSNA) in Wistar rats. In contrast, microinjection of
      an ErbB2 or ErbB4 inhibitor into the RVLM increased arterial pressure, HR, and
      RSNA. ErbB2 expression levels in the brainstem were significantly lower in
      spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rats. Depressor
      responses to NRG-1 and pressor responses to the ErbB2 inhibitor were
      significantly smaller in SHRs than in WKY rats (P < 0.05). Furthermore, the
      inhibition of ErbB2 expression in the RVLM by RNA interference significantly
      increased arterial pressure, HR, and urinary norepinephrine excretion in
      conscious WKY rats (P < 0.01). CONCLUSION: Our findings indicate that the NRG
      1/ErbB signaling in the RVLM has depressor and sympathoinhibitory effects.
      Reduced NRG/ErbB2 signaling in the RVLM may contribute to the neural mechanisms
      of hypertension.

PMID- 21738057
TI  - Missed nursing care, staffing, and patient falls.
AB  - Patient falls in hospitals continue to be a major and costly problem. This study
      tested the mediating effect of missed nursing care on the relationship of
      staffing levels (hours per patient day [HPPD]) and patient falls. The sample was
      124 patient units in 11 hospitals. The HPPD was negatively associated with
      patient falls (r = -0.36, P < .01), and missed nursing care was found to mediate
      the relationship between HPPD and patient falls.

PMID- 21738058
TI  - Orthopaedic Vendor Fairs.

PMID- 21738059
TI  - Orthopaedic trauma association basic science focus forum, 2010.

PMID- 21738060
TI  - Can we trust ex vivo mechanical testing of fresh--frozen cadaveric specimens? The
      effect of postfreezing delays.
AB  - BACKGROUND: Because embalming has been demonstrated to decrease the mechanical
      integrity of bone, most investigators favor fresh-frozen specimens for
      biomechanical evaluation. However, little is known about how the integrity of
      fresh--frozen specimens may change during biomechanical testing or may be
      affected by standard practices in testing. OBJECTIVE: The purpose of this study
      was to evaluate how the time after removal from a freezer may affect the
      mechanical properties of fresh--frozen diaphyseal bone. METHODS: Matched pairs of
      nonosteoporotic fresh--frozen human cadaveric femora were thawed before
      instrumentation with bicortical screws. Matched femora were reserved for either
      control or delayed use. Each specimen received standard diaphyseal bicortical
      screws (six or more in each group). At specified time points, screws were axially
      pulled out following the guidelines of ASTM F543-07. Test groups were stored in
      air (21 +/- 0.5 degrees C) for 16, 50, or 90 hours. In the control group, screws
      were pulled out at 16 hours, which corresponds to the minimum elapsed time for
      specimen thawing, instrumentation, potting, and biomechanical test initiation.
      This represents the baseline mechanical properties of the fresh--frozen bone at
      the inception of any biomechanical test. The 90-hour group corresponds to the
      time needed to cycle a construct 300,000 times at a physiological test frequency
      of 1 Hz. This corresponds approximately to 2 to 4 months of in vivo loading. A
      midpoint of 50 hours was also tested, representing approximately 180,000 cycles.
      RESULTS: Failure for all specimens occurred as a result of bone failure at the
      screw-to-bone interface. There was a decrease in screw pullout strength as
      exposure time in air increased. The 50-hour test group showed a 9% decrease in
      screw pullout strength as compared with the 16-hour control group (P = 0.81).
      However, the 90-hour test group showed a 30% decrease in screw pullout strength
      as compared with the 16-hour control group (P = 0.04). CONCLUSION: This study
      indicates that when using fresh-frozen cadaveric bone in biomechanical tests to
      simulate the orthopaedic clinical setting, specimen exposure time should be
      considered. The timing of testing should be kept constant between specimens to
      allow for a proper comparison. Furthermore, for fresh--frozen cadavers, the
      physical properties of bone may be detrimentally affected in biomechanical
      testing that exceeds the 50-hour time point after removal from the freezer.

PMID- 21738061
TI  - Increasing vascularity to improve healing of a segmental defect of the rat femur.
AB  - BACKGROUND: Segmental bone loss remains a challenging clinical problem. A
      frequent mitigating factor is inadequate blood supply. Small molecules that
      activate the hypoxia-inducible factor pathway can be used to stimulate
      angiogenesis. We investigated an approach to promote healing using angiogenic and
      osteogenic compounds in combination with a biodegradable, weightbearing scaffold.
      METHODS: Adult rats underwent removal of a 5-mm segment of femur stabilized by a
      cylindrical biodegradable implant and intramedullary fixation. Treatment groups
      included 1) saline (negative control); 2) desferrioxamine (DFO, a hypoxia
      inducible factor activator; 3) low-dose recombinant human bone morphogenetic
      protein-2 (rhBMP-2) (5 MUg); 4) DFO and low-dose rhBMP-2 (5 MUg); or 5) rh-BMP-2
      (10 MUg). Angiography was used to evaluate vascularity. Bone healing was assessed
      by radiographs, microcomputed tomography, histology, and biomechanical testing.
      RESULTS: Increased vascularity was seen at 6 weeks in the DFO treatment group.
      There appeared to be increased bone bridging as assessed by radiographic scores
      and microcomputed tomography in the BMP groups, although the quantification of
      bone volume did not show statistically significant differences. Biomechanical
      testing revealed improved stiffness in the treatment groups. CONCLUSIONS: DFO
      improved angiogenesis and stiffness of bone healing in segmental defects. BMP
      improved radiographic scores and stiffness. Use of angiogenic compounds in
      segmental bone loss is promising. CLINICAL RELEVANCE: Activation of the hypoxia
      inducible factor pathway may prove useful for bone defects, particularly where
      impaired blood supply exists.The low-cost approach could be useful in segmental
      bone defects clinically.

PMID- 21738062
TI  - Preclinical animal models in trauma research.
AB  - Preclinical modeling of human disease with animals has not been standardized for
      many common pathologic processes. Assorted animal models are being used to
      investigate the pathogenesis, prevention, and treatment of disease processes.
      Certainly it is difficult to interpret the current literature because there are
      diverse and often irrelevant models being implemented. Some models are used for
      reasons of size or ease rather than the true modeling of a physiological process.
      Application to granting agencies and design of animal studies is difficult
      without standardization of the ideal preclinical model for disease states. The
      current article addresses the preclinical animal modeling of osteoporosis,
      infection, bone defects, and cartilage injury. This article is a discussion of
      the current literature, commonly used models, and suggests preferred preclinical
      models for future research design.

PMID- 21738063
TI  - Mechanical stability affects angiogenesis during early fracture healing.
AB  - OBJECTIVES: The goal of this study was to determine to what extent mechanical
      stability affects vascular repair during fracture healing. METHODS: Stabilized
      and nonstabilized tibia fractures were created in adult mice. Fracture tissues
      were collected at multiple time points during early fracture healing. Vasculature
      in fractured limbs was visualized by immunohistochemistry with an anti-PECAM-1
      antibody on tissue sections and then quantified with stereology. Oxygen tension,
      vascular endothelial growth factor expression, and lactate accumulation at the
      fracture site were measured. Gene expression was compared between stabilized and
      nonstabilized fractures by microarray analysis. RESULTS: We found that new blood
      vessel formation was robust by 3 days after fracture. Quantitative analysis
      showed that nonstabilized fractures had higher length density and surface density
      than stabilized fractures at 3 days after injury, suggesting that nonstabilized
      fractures were more vascularized. Oximetry analysis did not detect a significant
      difference in oxygen tension at the fracture site between stabilized and
      nonstabilized fractures during the first 3 days after injury. Further microarray
      analysis was performed to determine the effects of mechanical stability on the
      expression of angiogenic factors. No significant difference in the expression of
      vascular endothelial growth factors and other angiogenic factors was detected
      between stabilized and nonstabilized fractures. CONCLUSIONS: Mechanical
      instability promotes angiogenesis during early fracture healing and further
      research is required to determine the underlying mechanisms.

PMID- 21738064
TI  - Androstenediol exerts salutary effects on chemokine response after trauma
      hemorrhage and sepsis in mice.
AB  - OBJECTIVES: The pathogenesis of multiple organ dysfunction syndrome and sepsis
      after polytrauma is related to the posttraumatic immune response and the
      associated release of inflammatory mediators. There exists a gender dimorphism in
      the posttraumatic host response. Sex steroids are believed to beneficially
      modulate the posttraumatic immune response. The specific effect of androstenediol
      on chemokines after trauma is unknown. We investigated whether the application of
      androstenediol has an effect on plasma chemokine levels and the associated remote
      organ damage in a two-hit mouse-model of trauma-hemorrhage, cecal ligation, and
      cecal puncture. MATERIALS AND METHODS: Traumatic hemorrhage was induced followed
      by androstenediol application and volume resuscitation. Thereafter,
      androstenediol was given once daily in combination with a vehicle (Intralipid).
      The control group was injected with a solution containing only the vehicle at the
      same time points as the treatment groups' androstenediol applications. Sepsis was
      induced by cecal ligation and cecal puncture 48 hours afterward. Four hours after
      cecal ligation and cecal puncture, plasma measurements of chemokines were
      performed. Pulmonary infiltration by polymorphonuclear lymphocytes was measured
      by immunhistochemical staining and myeloperoxidase measurements were taken.
      RESULTS: Application of androstenediol led to significantly decreased monocyte
      chemoattractant protein-1, monocyte chemoattractant protein-3, macrophage
      inflammatory protein-1alpha, and macrophage inflammatory protein-1beta levels
      compared with the control animals after trauma-hemorrhage, cecal ligation, and
      cecal puncture (P < 0.05). Pulmonary infiltration and myeloperoxidase activity
      were significantly decreased in androstenediol-treated animals (P < 0.05).
      CONCLUSION: Androstenediol modulates the immune response after trauma-hemorrhage,
      cecal ligation, and cecal puncture by reducing systemic chemokine levels, which
      are known to direct immune cells into the tissue possibly leading to organ
      damage. Androstenediol represents a potential therapeutic agent after major
      trauma in high-risk patients.

PMID- 21738065
TI  - Managing bone defects.
AB  - The management of bone defects caused by trauma and nonunion continues to
      represent a substantial clinical challenge in the management of orthopaedic
      trauma patients. A variety of treatment options have been described and reported
      in the literature. The relative rarity of these injuries means that high level,
      comparative evidence to guide their management is sparse. As such, treatment
      decisions must be based on knowledge of the available evidence, contemporary
      fracture management principles, and consideration of patient and surgeon factors.
      This article reviews the available evidence for the different treatment options
      available for the management of bone defects.

PMID- 21738066
TI  - Xenograft bone inclusion improves incorporation of hydroxyapatite cement into
      cancellous defects.
AB  - OBJECTIVES: Hydroxyapatite cement (HAC) is biocompatible and osteoconductive, but
      its slow resorption limits new bone formation. The purpose of this investigation
      was to determine the effects of adding partially demineralized xenograft cortical
      bone in an established animal model. METHODS: Eight 6-month-old female New
      Zealand white rabbits were used. Drill-hole defects (8.0 mm long, 5.0 mm
      diameter) were prepared and filled with either HAC alone or HAC mixed with
      processed xenograft bone particles from young pigs (XBC) at a volumetric ratio of
      approximately 25%. The particles were approximately 5 mm long and 1 mm diameter
      and were extensively washed, demineralized in dilute hydrochloric acid, and
      rewashed. Microcomputed tomography scanning and histology were performed after 10
      weeks. New bone and inflammatory/immune response were graded on a 0 to 3 scale
      and calcein labeling was quantified as percent area new bone. Statistical
      analyses were by Student's t tests. RESULTS: XBC showed significantly more new
      bone formation than HAC throughout the defect (P < 0.05). XBC also showed
      significantly more inflammatory/immune response than HAC (P < 0.05). The three
      dimensional microcomputed tomography reconstructions showed that the HAC was
      basically inert, whereas the XBC took on an appearance suggestive of more
      extensive incorporation. CONCLUSIONS: Adding xenograft to HAC creates a bioactive
      composite that is more rapidly incorporated, resorbed, and replaced by new bone.
      The presence of processed xenograft particles creates a vigorous inflammatory
      response, but there may be some benefit to the resorption rate of the HAC as a
      result of the infiltration of cells. Future research should focus on the longer
      term incorporation and remodeling of XBC.

PMID- 21738067
TI  - Murine model of oligotrophic tibial nonunion.
AB  - OBJECTIVES: This study aimed to use modified distraction osteogenesis techniques
      to develop a reliable mouse fracture nonunion model with an oligotrophic
      phenotype. METHODS: Twenty-six 10- to 14-week-old C57BL/6 male mice underwent a
      proximal diaphyseal tibial osteotomy with a 2-mm bone resection. An external
      fixation device was applied to the tibia using cerclage wires. A total of 2.25 mm
      of distraction was applied over 3 days, resulting in an average distraction gap
      of 4.28 mm. Plain radiographs were taken at regular intervals until euthanasia at
      7 (n = 9), 10 (n = 13), or 12 (n = 4) weeks. After euthanasia, all samples were
      fixed in formalin, scanned with microcomputed tomography, decalcified in formic
      acid, prepared in paraffin, and stained with Alcian blue/Mayer's hematoxylin.
      RESULTS: In the distraction groups, five mice were prematurely euthanized as a
      result of wound complications stemming from loss of distal fixation. Of the
      remaining 21, two healed, resulting in a 90% nonunion rate. These nonunions
      radiographically resembled clinical nonunions with tapered, cone-like fracture
      ends and histologically demonstrated evidence of attempted healing as seen with
      cartilage capping. Additionally, the plain radiographic appearance of those
      nonunions from mice euthanized at 10 and 12 weeks did not change over the final 4
      to 6 weeks. CONCLUSIONS: The use of 2-mm tibial resection osteotomy with 2-mm
      distraction provides a predictable model for fracture nonunion in mice with the
      oligotrophic phenotype closely resembling the clinical correlate. This model
      offers a promising means for characterization of the molecular events that occur
      during the development of fracture nonunion and for evaluation of noninvasive
      methods of nonunion rescue.

PMID- 21738068
TI  - Antioxidant therapy attenuates deficient bone fracture repair associated with
      binge alcohol exposure.
AB  - OBJECTIVES: Alcohol consumption is a known risk factor for traumatic injuries of
      all types and has been shown to produce detrimental effects on bone metabolism.
      Although the mechanisms responsible for these detrimental effects are not well
      characterized, oxidative stress from alcohol exposure appears to play a central
      role. This study was designed to examine the effect of a short-term binge alcohol
      consumption pattern on fracture repair and the effect of an antioxidant, N
      acetylcysteine, on fracture healing after binge alcohol consumption. METHODS: One
      hundred forty-four adult male Sprague-Dawley rats underwent unilateral closed
      femur fracture after injection of either saline or alcohol to simulate a binge
      alcohol cycle. Animals in the antioxidant treatment group received daily N
      acetylcysteine after fracture. Femurs were harvested at 1, 2, 4, and 6 weeks
      after injury and underwent biomechanical testing and histologic analysis.
      RESULTS: Binge alcohol administration was associated with significant decreases
      in biomechanical strength at 1- and 2-week time points with a trend toward
      decreased strength at 4- and 6-week time points as well. Alcohol-treated animals
      had less cartilage component within the fracture callus and healed primarily by
      intramembranous ossification. Administration of N-acetylcysteine in alcohol
      treated animals improved biomechanical strength to levels comparable to the
      control animals and was associated with increased endochondral ossification.
      CONCLUSIONS: Our results indicate that binge alcohol alters the quality of
      fracture healing after a traumatic injury and that concurrent administration of
      an antioxidant is able to reverse these effects.

PMID- 21738069
TI  - Heterotopic ossification after extremity blast amputation in a Sprague-Dawley rat
      animal model.
AB  - OBJECTIVE: To create an animal survival model for heterotopic ossification (HO)
      in the residual limb of the rat after extremity blast amputation. The hypothesis
      was that extremity blast amputation spontaneously stimulates development of HO in
      the residual limb. METHODS: Twelve Sprague-Dawley rats underwent localized
      exposure to a controlled, high-energy blast. Seven rats were designated for hind
      limb amputation and five for forelimb amputation. Our protocol produced extremity
      amputation through detonation of an explosive while protecting the animal
      proximal to the specified amputation level. Immediately after injury, the rat
      underwent wound management and primary surgical closure. Radiographs of the
      amputated limbs were obtained every 2 weeks. Heterotopic bone was
      radiographically classified as periosteal growth (Type A) or noncontiguous growth
      (Type B). A kappa statistic was calculated for interobserver strength of
      agreement on the presence of HO. Fisher exact test was conducted to assess the
      significance of the difference in hind limb and forelimb HO rates. RESULTS: Nine
      of 12 animals survived the procedure. The three nonsurvivors were all hind limb
      amputees, and each died of various related causes. All four surviving hind limb
      amputees exhibited Type A HO, and three of four also exhibited Type B HO within
      the injured stump. One of five forelimb amputees exhibited Types A and B HO.
      CONCLUSIONS: We have developed a reproducible model for HO in the residual limbs
      of blast-amputated rats without addition of exogenous osteogenic stimulus. Hind
      limb amputation demonstrated a predilection for HO formation in comparison with
      forelimb amputation (P < 0.05).

PMID- 21738070
TI  - Dual-purpose bone grafts improve healing and reduce infection.
AB  - OBJECTIVE: To determine if a dual-purpose bone graft can regenerate bone and
      reduce infection in highly contaminated bone critical size defects in rats.
      METHODS: Biodegradable polyurethane (PUR) scaffolds were loaded with recombinant
      human bone morphogenetic protein-2 (BMP-2) and vancomycin (Vanc). The release
      kinetics of the BMP-2 were tuned to take advantage of its mechanism of action
      (ie, an initial burst to recruit cells and sustained release to induce
      differentiation of the migrating cells). The Vanc release kinetics were designed
      to protect the graft from contamination until it is vascularized by having a
      burst for a week and remaining well over the minimum inhibitory concentration for
      Staphylococcus aureus for 2 months. The bone regeneration and infection reduction
      capability of these dual-purpose grafts (PUR+Vanc+BMP-2) were compared with
      collagen sponges loaded with BMP-2 (collagen+BMP-2) and PUR+BMP-2 in infected
      critical size rat femoral segmental defects. RESULTS: The dual-delivery approach
      resulted in substantially more new bone formation and a modest improvement in
      infection than PUR+BMP-2 and collagen+BMP-2 treatments. CONCLUSIONS: The PUR bone
      graft is injectable, provides a more sustained release of BMP-2 than the collagen
      sponge, and can release antibiotics for more than 8 weeks. Thus, the dual
      delivery approach may improve patient outcomes of open fractures by protecting
      the osteoinductive graft from colonization until vascularization occurs. In
      addition, the more optimal release kinetics of BMP-2 may reduce nonunions and the
      amount of growth factor required.

PMID- 21738071
TI  - Endothelial progenitor cells for fracture healing: a microcomputed tomography and
      biomechanical analysis.
AB  - PURPOSE: Local treatment of segmental bone defects with ex vivo expanded
      endothelial progenitor cells (EPCs) has been shown to increase osteogenesis and
      callus formation in rat femur diaphyseal defects. The purpose of this study was
      to evaluate the effects of local EPC therapy on the microarchitecture and
      biomechanical properties of a segmental bone defect in a rat model. METHODS: Five
      millimeter segmental defects were created in the femora of 14 Fisher 344 rats and
      stabilized with miniplates. The treatment group (n = 7) received 1 * 10(6) EPCs,
      seeded on a Gelfoam scaffold, locally at the site of the bone defect, and control
      animals (n = 7) received Gelfoam and saline only. Animals were euthanized 10
      weeks after the procedure and new bone formation was assessed with radiographs,
      microcomputed tomography and biomechanical testing. RESULTS: Radiographically,
      all the animals in the EPC-treated group healed with bridging callus formation,
      whereas animals in the control group developed nonunion of the defect.
      Microcomputed tomography assessment demonstrated significantly superior bone
      formation in the EPC-treated group versus the control group for all parameters
      tested (P = 0.013-0.000). Biomechanical testing revealed that the EPC-treated
      group had significantly higher torsional strength (P = 0.000) and stiffness (P =
      0.000) when compared with the control group. CONCLUSION: The results of this
      study suggest that local EPC therapy significantly enhances fracture healing in a
      segmental defect model in a rat femur. EPC therapy results in superior
      radiographic bone formation and healing when compared with appropriate controls.

PMID- 21738072
TI  - Clinician personality and the evaluation of higher-risk patient symptoms.
AB  - BACKGROUND: : Acute myocardial infarction, breast cancer, and colorectal cancer
      are among the most commonly misdiagnosed conditions in primary care, and there is
      little information regarding physician decision making in this area. METHODS: :
      We measured clinician risk tolerance and stress from uncertainty among 193
      primary care clinicians and determined their association with management of
      patients presenting with chest pain (n = 700), breast lumps (n = 630), or rectal
      bleeding (n = 470). We used the 6-item Jackson Personality Inventory (JPI) and
      the 13-item Stress from Uncertainty Scale (SUS). Extended evaluation was defined
      as performance of electrocardiogram, cardiac stress testing, or emergency
      department triage for patients with chest pain; mammography, ultrasound, or
      surgical referral for patients with breast lumps; and colonoscopy or
      gastroenterology referral for patients with rectal bleeding. We fit multivariable
      logistic regression models to determine the association between survey scores and
      performance of extended evaluation. RESULTS: : The response rate was 79% for the
      JPI survey and 73% for the SUS survey. The mean JPI score was 8.9 (SD, 4.5) and
      the mean SUS score was 32.6 (SD, 10.4). Extended evaluation occurred for 60% of
      patients with chest pain, 93% of patients with breast lumps, and 63% of patients
      with rectal bleeding. Scores in JPI and SUS were not associated with rates of
      extended evaluation. CONCLUSIONS: : Primary care clinician risk tolerance and
      stress from uncertainty were not associated with evaluation decisions. Future
      research is needed to improve the consistency of evaluations to improve
      ambulatory patient safety.

PMID- 21738073
TI  - Preparing the lumbar intervertebral disk space for interbody procedures: a
      comparison between the traditional method and a new automated method.
AB  - STUDY DESIGN: Cadaveric laboratory study. OBJECTIVE: To quantify and compare
      automated disk-space preparation with traditional methods. SUMMARY OF BACKGROUND
      DATA: Removal of nucleus pulposus to prepare a disk space for interbody fusion is
      performed with various techniques. Our aim was to determine the safety and
      effectiveness of an automated technique in comparison to traditional methods and
      gauge its expected clinical application. METHODS: This study was conducted in 2
      phases. In the phase 1 safety trial, ''maximal'' force was applied to an
      automated shaver against cadaveric annulus and endplates until flexion of the
      shaft caused the blades to bind. This simulated the risk of creating an
      incidental cortical or annular defect. In phase 2, 27 cadaveric lumbar disk
      spaces were randomized to traditional or automated preparation techniques through
      a standard transforaminal lumbar interbody fusion approach. Traditional method
      comprised the use of paddle shavers, pituitary rongeurs, and curettes. Automated
      technique involved insertion of an 8-mm paddle shaver, followed by straight and
      angled hand pieces to remove nucleus pulposus and endplate cartilage. Unintended
      cortical and annular breaches, preparation time, instrument insertions,
      percentage area of exposed endplate underlying the nucleus pulposus, and
      percentage volume of nuclear space cleared were measured and compared. RESULTS:
      In phase 1, ''maximal'' force applied for 10 seconds produced no full-thickness
      annular or cortical defects. In phase 2, automated technique produced fewer
      endplate cortical defects (3 vs. 7) and full-thickness annular breaches (0 vs.
      1), required fewer instrument insertions (29 vs. 6; P<0.001), exposed more
      endplate (65% vs. 52%; P=0.037), and removed more nucleus pulposus volume (83%
      vs. 59%; P=0.01). CONCLUSIONS: Automated shaving decreased instrument insertions
      and prepared the disk space more effectively, with fewer cortical or annular
      defects. This technique holds promise for improved outcomes in spinal fusion
      surgery.

PMID- 21738074
TI  - Effect of total lumbar disc replacement on lumbosacral lordosis.
AB  - STUDY DESIGN: Original article OBJECTIVE: : To study effect of lumbar disc
      replacement on lumbosacral lordosis. SUMMARY OF BACKGROUND DATA: There has been a
      growing interest in total disc replacement (TDR) for back pain with the rising
      concern of adjacent segment degeneration. Lumbar fusion surgery has been shown to
      lead to decrease in lumbar lordosis, which may account for postfusion pain
      resulting in less acceptable clinical outcome after successful fusion. TDR has
      recently emerged as an alternative treatment for back pain. There have been very
      few studies reporting lumbar sagittal outcome after TDR. METHODS: Retrospective
      study of radiographic data of 17 patients who underwent TDR for single level
      degenerative disc disease at the author's institution was carried out. Study
      included measurement of preoperative and postoperative segmental and global
      lumbar lordosis and angle of lordosis. RESULTS: Patients age varied from 19 to 54
      (mean, 35) years. Follow-up ranged from 12 to 24 months. TDR was performed at L4
      5 level in 3 patients and L5-S1 level in 14 patients. The average values for
      segmental lordosis, global lordosis, and angle of lordosis at the operated level
      before and after surgery were 17.3, 49.7, and 8.6 degrees and 21.6, 54, and 9.5
      degrees, respectively. There was a trend toward significant (P=0.02) and near
      significant (P=0.057) increase in segmental and global lordosis, respectively
      after TDR. Although prosthesis increased angle of lordosis at the level implanted
      in majority of the patients, the difference in preoperative and postoperative
      angle of lordosis was not significant (P=0.438). In addition, there was no
      correlation between the angle of implant of chosen and postoperative angle of
      lordosis at the operated level. CONCLUSIONS: The effect of TDR on sagittal
      balance appears favorable with an increase in global and segmental lumbar
      lordosis after single level TDR for degenerative disc disease. The degree of
      postoperative angle of lordosis was not affected by the angle of implant chosen
      at the operated level and varied independently of the implant angle.

PMID- 21738075
TI  - A novel technique for temporary fixation during posterolateral thoracic
      corpectomy.
AB  - STUDY DESIGN: Description of novel technique. OBJECTIVE: The objective of this
      study is to describe a novel technique of temporary fixation for posterolateral
      thoracic corpectomy. SUMMARY OF BACKGROUND DATA: Posterolateral approaches have
      been used to successfully perform thoracic corpectomies for a variety of
      pathologies. As currently described, these approaches require the use of
      temporary fixation, usually in the form of unilateral pedicle screws and rod. One
      limitation of this technique is that the vertebral body may only be approached
      from one side at a time, as the temporary fixation rod obstructs the view of the
      surgeon or the assistant. METHODS: The authors introduce a novel technique for
      temporary fixation during posterolateral thoracic corpectomy. A series of 8
      patients is presented in whom a temporary fixation cross-rod was placed
      diagonally between cephalad and caudad contralateral pedicle screws. This allowed
      simultaneous access to the vertebral bodies by 2 surgeons, thereby improving
      exposure and decreasing operative time and estimated blood loss. RESULTS: There
      were no complications related to temporary fixation during the procedures, and no
      translational movement was observed. CONCLUSIONS: Diagonal temporary rod fixation
      is a useful modification of standard posterolateral thoracic corpectomy
      techniques that allows simultaneous bilateral access for vertebral body
      resection.

PMID- 21738076
TI  - Surgical correction of spinal deformity in patients with cerebral palsy using
      pedicle screw instrumentation.
AB  - STUDY DESIGN: Retrospective review of a prospectively collected single surgeon's
      series. OBJECTIVE: To investigate the efficacy of pedicle screw instrumentation
      in correcting spinal deformity in patients with quadriplegic cerebral palsy. In
      addition to assess quality-of-life and functional improvement after deformity
      correction as perceived by the parents of our patients. SUMMARY OF BACKGROUND
      DATA: All pedicle screw constructs have been commonly used to correct adolescent
      idiopathic scoliosis. There is limited information on their effectiveness in
      treating patients with cerebral palsy and neuromuscular scoliosis. METHODS: We
      reviewed the medical records and serial radiographs of 45 consecutive patients
      with quadriplegia who underwent spinal arthrodesis using pedicle screw/rod
      instrumentation and a standardized surgical technique. All patients were
      wheelchair bound with collapsing thoracolumbar scoliosis and pelvic obliquity.
      Twenty-eight patients had associated sagittal deformities. A telephone survey was
      performed by an independent investigator to assess parents' perception on
      surgical outcome. RESULTS: Thirty-eight patients underwent posterior-only and 7
      staged anteroposterior spinal arthrodesis. Mean age at surgery was 13.4 years
      (range: 9 to 18.3 y) and mean postoperative follow-up was 3.5 years (range: 2.8
      to 5 y). Pedicle screw instrumentation extended from T2/T3 to L5 with bilateral
      pelvic fixation using iliac bolts. Scoliosis was corrected from mean 82.5 to 21.4
      degree (74.1%). Pelvic obliquity was corrected from mean 24 to 4 degree (83.3%).
      In posterior-only procedures, average blood loss was 0.8 blood volumes, intensive
      care unit stay 3.5 days, and hospital stay 17.6 days. In anteroposterior
      procedures, average blood loss was 0.9 blood volumes, intensive care unit stay
      8.9 days, and hospital stay 27.4 days. Major complications included 1 deep
      infection and 1 reoperation to remove prominent implants but no deaths, no
      neurological deficit, and no detected pseudarthrosis. Parents' survey showed 100%
      satisfaction rate. CONCLUSIONS: Pedicle screw instrumentation can achieve
      excellent correction of spinal deformity in quadriplegic cerebral palsy with low
      complication and re-operation rates and high parent satisfaction.

PMID- 21738077
TI  - The TU-025 keishibukuryogan clinical trial for hot flash management in
      postmenopausal women: results and lessons for future research.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of TU-025,
      keishibukuryogan, a Japanese prescription herbal medicine used for hot flash
      management, in American women. METHODS: This randomized, double-blind, placebo
      controlled, phase II trial enrolled 178 postmenopausal women aged 45 to 58 years
      with a Mayo hot flash score greater than 28 per week who met other inclusion
      criteria. After a 1-week placebo run-in period, participants were randomly
      assigned placebo, or 7.5 g/day, or 12.5 g/day groups, for 12 weeks. Primary and
      secondary outcomes were measured using the Mayo Clinic Hot Flash Diary, the
      Greene Climacteric Index, and the Pittsburgh Sleep Quality Index. RESULTS: At 3
      months, hot flash scores, climacteric symptoms, and sleep quality improved by 34%
      in the placebo group, 40% in the 7.5 g/day group, and 38% in the 12.5 g/day
      group. (P < 0.001). However, the differences in changes between groups were not
      statistically significant (P = 0.990). Diarrhea unexpectedly developed in 20% of
      participants receiving active medication. CONCLUSIONS: For American women, unlike
      the clinical experience for Japanese women, TU-025 did not significantly reduce
      the frequency and severity of hot flash symptoms, improve climacteric symptoms,
      or benefit sleep quality. This study identified several potentially significant
      methodological factors to be considered in future scientific assessments of
      traditional Asian medicines.

PMID- 21738078
TI  - Increased incident hip fractures in postmenopausal women with moderate to severe
      pelvic organ prolapse.
AB  - OBJECTIVE: The aim of this study was to examine the association between fracture
      and pelvic organ prolapse (POP) in postmenopausal women enrolled in the Women's
      Health Initiative Estrogen Plus Progestin trial. METHODS: POP was assessed as
      cystocele, rectocele, or uterine prolapse and was graded as either "absent to
      mild" or "moderate to severe." Cox proportional hazard analyses (adjusting for
      age, body mass index, race, asthma, emphysema, thyroid disease, family history of
      fracture, regular menses, age at menopause, nulliparity, history of hormone
      therapy [HT], history of falls, socioeconomic status, calcium, and vitamin D
      supplementation and physical activity) explored the relationships between
      moderate to severe POP and incident bone fractures. RESULTS: Moderate- to severe
      grade POP was identified in almost 8% of women (n = 1,192). During a follow-up
      duration of 7.41 (2.18) years (mean [SD]), 2,156 incident fractures were
      observed; the most common fracture site was the lower arm (n = 615; 28.51%)
      followed by the hip (n = 205; 9.51%). Adjusted analyses confirmed moderate to
      severe POP (of any type) as an independent risk factor for incident hip fractures
      (hazard ratio [HR], 1.83; 95% CI, 1.16-2.89; P = 0.010). On analyses stratified
      by assigned treatment (HT vs placebo), moderate to severe rectocele emerged as an
      independent predictor of incident spine (HR, 2.61; 95% CI, 1.04-6.56; P = 0.042)
      and lower arm fractures (HR, 1.87; 95% CI, 1.06-3.29; P = 0.030) in the placebo
      group. CONCLUSIONS: We identify moderate to severe POP (any type) in
      postmenopausal women as a risk factor for hip fracture; moderate to severe
      rectocele holds an additional risk of spine and lower arm fractures in women not
      taking HT.

PMID- 21738079
TI  - Estrogen receptor beta-selective phytoestrogenic formulation prevents physical
      and neurological changes in a preclinical model of human menopause.
AB  - OBJECTIVE: As an alternative to estrogen therapy, the efficacy of an estrogen
      receptor beta-selective phytoestrogenic (phyto-beta-SERM) formulation to regulate
      climacteric symptoms and decline in brain responses associated with ovarian
      hormone loss in menopause was assessed. METHODS: A phyto-beta-SERM formulation
      containing diet was compared with a commercial soy extract diet and a
      phytoestrogen-free base/control diet in an ovariectomized (OVX) mouse model of
      human menopause. Two treatment studies were conducted: (1) a 2-month study
      assessed the effects of experimental diets on tail skin temperature as a model of
      menopausal hot flashes, and (2) a 9-month study assessed the long-term impact of
      the diets on overall health, hair thinning/loss, spatial working memory, and
      associated protein expression in the hippocampus. RESULTS: The phyto-beta-SERM
      diet prevented OVX-induced menopause-like changes including the rise in skin
      temperature, hair thinning/loss, deficit in spatial memory function, and reversed
      OVX-induced decline in the expression of hippocampal proteins involved in neural
      plasticity and beta-amyloid degradation/clearance. The soy extract diet had no
      effect or exacerbated OVX-induced changes. CONCLUSIONS: Overall, the phyto-beta
      SERM diet induced physical and neurological responses comparable with ovary
      intact mice, suggesting the therapeutic potential of the phyto-beta-SERM
      formulation for the prevention/alleviation of climacteric symptoms and decline in
      brain responses induced by ovarian hormone loss, which provides the basis for
      further work in postmenopausal women.

PMID- 21738080
TI  - Association of Cullin1 haplotype variants with rheumatoid arthritis and response
      to methotrexate.
AB  - Aberrations in ubiquitin pathway have been implicated in many diseases and drug
      response. In a previous study on rheumatoid arthritis (RA) in Japanese
      population, significant association of Cullin1 gene (CUL1), an ubiquitin E3
      ligase, was observed. CUL1 also mediates degradation of IkappaBalpha and p27,
      levels of which has been associated with RA etiology and drug response,
      respectively. We carried out a replication study of association of CUL1
      polymorphisms with RA in a north Indian population. Allelic, genotypic, and
      haplotypic associations of a promoter and two intronic polymorphisms of CUL1 with
      RA and with methotrexate response in patients with RA, were tested. A significant
      association (P=0.00056, adjusted) of a haplotype A-T-T with RA (odds ratio=3.68;
      95% confidence interval=1.86-7.27) and in patients with RA poorly responding to
      methotrexate treatment (P=0.04, adjusted) was observed. Association with CUL1
      haplotype indicates a possible role of CUL1 variation(s) in RA and its response
      to methotrexate.

PMID- 21738081
TI  - PharmGKB summary:  carbamazepine pathway.

PMID- 21738082
TI  - The TallyHo polygenic mouse model of diabetes: implications in wound healing.
AB  - BACKGROUND: Impairments in wound healing represent a significant source of
      morbidity and mortality in patients with diabetes. To help uncover the
      derangements associated with diabetic wound healing, murine animal models have
      been extensively used. In this article, the authors present results, and the
      accompanying wound healing implications, from experiments across three validated
      wound healing models using a newer polygenic strain of diabetes. METHODS: The
      authors investigated the wound healing impairments of the TallyHo/JnJ diabetic
      mouse strain, using three validated wound healing models: an incisional model, a
      splinted excisional model, and a cutaneous ischemia-reperfusion injury model.
      Appropriate control strain mice were used for comparison. Wounds were analyzed
      using gross, histologic, and molecular techniques. RESULTS: TallyHo mice
      displayed deficits across all three wound healing models. There was a reduced
      resistance/response to oxidative stress and a global decrease in the initial
      inflammatory response to healing. In addition, there was a global decrease in the
      stimulus for angiogenesis and collagen formation, ultimately leading to reduced
      reepithelialization, granulation tissue formation, wound contraction, and wound
      tensile strength. Gross and histologic findings were corroborated with molecular
      data, which revealed a significant down-regulation of important cytokines,
      including vascular endothelial growth factor, neutrophilic attractant protein-2,
      monocyte chemoattractant protien-1, heme oxygenase-1, interleukin-1beta, and
      interleukin-6, when normalized to the control strain (p<0.05). CONCLUSIONS: The
      TallyHo polygenic mouse model of diabetes demonstrates predictable and clinically
      relevant wound healing impairments that offer important implications into the
      derangements of diabetic wound healing observed clinically. Therapeutics
      targeting these specific derangements could provide improvements in the care of
      diabetic wounds.

PMID- 21738083
TI  - Guide to early surgical management of lip hemangiomas based on our experience of
      214 cases.
AB  - BACKGROUND: Hemangiomas are the most common vascular lesions in infancy. The
      majority of hemangiomas occur on the face and cause significant parental distress
      because of their high visibility. Traditionally, they have been managed by a
      "watch and wait" approach due to their known propensity to improve significantly
      over time. This is a particularly difficult approach for hemangiomas of the lips
      due to their high visibility and their tendency to leave residual deformity even
      after resolution. METHODS: The authors performed a retrospective chart review of
      pediatric patients who underwent surgical excision of upper and lower lip
      hemangiomas at Children's Hospital Los Angeles between 1992 and 2006. RESULTS:
      The authors identified 214 patients with an average age of 23.6 months at the
      time of surgery. All patients had improvements in lip appearance, with minimal
      complications. No transfusions were required, and all but two patients (lip
      switch flaps for major tissue loss) were managed on an outpatient basis. Overall,
      complications were minimal, with a high degree of parent satisfaction.
      CONCLUSION: The authors conclude that many children would benefit from early
      excision and present guidelines for the early surgical management of lip
      hemangiomas.

PMID- 21738084
TI  - Changing practice:  implementation of a venous thromboembolism prophylaxis
      protocol at an academic medical center.
AB  - BACKGROUND: The Institute of Medicine has identified a "quality chasm" between
      existing evidence and actual clinical practice. The Venous Thromboembolism
      Prevention Study has shown that enoxaparin prophylaxis is a safe and effective
      way of preventing postoperative venous thromboembolism. This article presents a
      "how-to" guide for implementation of a venous thromboembolism prophylaxis
      protocol. METHODS: The Venous Thromboembolism Prevention Study prophylaxis
      protocol included provision of postoperative, prophylactic dose enoxaparin for
      the duration of inpatient stay. Compliance was considered at the individual
      patient level and defined as appropriate provision of protocol-appropriate
      enoxaparin prophylaxis. Multiple simultaneous interventions to improve protocol
      compliance were undertaken. Both physician and physician assistant "champions"
      were identified. Interventions included staff and surgeon educational sessions,
      discussion of venous thromboembolism-themed articles at journal club, and monthly
      e-mail reminders specific to the protocol, among others. Compliance rates over
      time were compared using the chi-square test. RESULTS: The authors reviewed
      medical records from 945 consecutive admissions to the plastic surgery service
      who met Venous Thromboembolism Prevention Study eligibility criteria over a 30
      month period. Initial education sessions significantly increased compliance over
      baseline (55 percent versus 10 percent; p<0.001). After formal protocol adoption,
      compliance increased steadily over the first 9 months and peaked by 1 year. In
      the absence of any direct intervention, compliance remained stable at 90 percent
      for the final 12 months of the study. This was significantly increased when
      compared with the period of time immediately following protocol adoption (90
      percent versus 77 percent; p<0.001). CONCLUSION: This article provides readers
      with a practical approach for implementation of a venous thromboembolism
      prophylaxis protocol at their hospital.

PMID- 21738085
TI  - Preliminary soft-tissue distraction versus checkrein ligament release after
      fasciectomy in the treatment of dupuytren proximal interphalangeal joint
      contractures.
AB  - BACKGROUND: Checkrein ligament release for treatment of proximal interphalangeal
      joint Dupuytren contractures does not address the shortened arteries or deficient
      skin. The Digit Widget uses soft-tissue distraction to overcome these issues.
      This study compares checkrein ligament release after fasciectomy versus
      preliminary soft-tissue distraction, followed by operative release, for treatment
      of proximal interphalangeal joint Dupuytren contractures. METHODS: The authors
      compared operative and postoperative characteristics of patients treated with
      either fasciectomy plus checkrein ligament release or Digit Widget distraction
      between 2001 and 2008. Seventeen patients (20 digits) underwent ligament release
      (mean contracture, 55.9 degrees); six of these 20 were reoperations. Thirteen
      patients (17 digits) underwent distraction (mean contracture, 67.6 degrees); 10
      of 17 were reoperations. RESULTS: The 20 digits treated with fasciectomy plus
      ligament release had an average extension improvement of 31.4 degrees (range, -4
      to 70 degrees). Digits treated with distraction had an average extension
      improvement of 53.4 degrees (range, 30 to 75 degrees) (p<0.001 versus ligament
      release). Three digits treated with distraction improved to full proximal
      interphalangeal extension. Initial contractures of 60 degrees or less treated by
      ligament release (n=12) or distraction (n=7) improved by means of 28.8 degrees
      and 47.7 degrees, respectively (p=0.048). Contractures greater than 60 degrees
      treated by ligament release (n=8) or distraction (n=10) improved by means of 35.3
      degrees and 57.3 degrees, respectively (p=0.02). CONCLUSION: Soft-tissue
      distraction followed by operative release showed greater correction than
      Dupuytren fasciectomy plus checkrein ligament release. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 21738086
TI  - Nipple-sparing mastectomy for prophylactic and therapeutic indications.
AB  - BACKGROUND: Nipple-sparing mastectomy remains controversial and its adoption has
      been slow because of oncologic and surgical concerns. METHODS: A retrospective
      study evaluated all nipple-sparing mastectomies performed at a single institution
      for therapeutic or prophylactic indications for which records were available.
      RESULTS: Between 1989 and 2010, 162 nipple-sparing mastectomies were performed in
      101 women. Forty-nine (30 percent) were performed for therapeutic purposes on 48
      patients. A subareolar biopsy specimen was taken in 39 of 49 breasts (80
      percent); four (10 percent) revealed ductal carcinoma in situ, and the nipple or
      nipple-areola complex was later removed. Four of 49 breasts (8 percent) in the
      therapeutic group had ischemic complications involving the nipple-areola complex,
      one of which (2 percent) was excised. With a mean follow-up of 2 years 6 months
      (range, 5 months to 9 years 5 months), no patients developed cancer in the nipple
      areola complex. The remaining 113 mastectomies (70 percent) were performed
      prophylactically on 80 patients. The subareolar tissue was biopsied in 80 breasts
      (71 percent). One biopsy revealed lobular carcinoma in situ; none had ductal
      carcinoma in situ or invasive cancer. Two nipple-areola complexes (1.8 percent)
      were ischemic and excised. With a mean follow-up of 3 years 7 months (range, 5
      months to 20 years 6 months), no patients developed new primary cancers in the
      nipple-areola complex. CONCLUSIONS: Nipple-sparing mastectomy can be safe in
      properly selected patients. A subareolar biopsy can effectively identify nipple
      areola complexes that may harbor cancerous cells. Ischemic complications
      resulting in nipple loss can be minimized, and long-term follow-up suggests that
      this technique deserves further investigation in properly selected patients.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 21738087
TI  - Factors contributing to migraine headache surgery failure and success.
AB  - BACKGROUND: The purpose of this study was to identify factors that contribute to
      migraine headache surgery failure and success. METHODS: A retrospective chart
      review was conducted of patients who underwent surgery for migraine headaches
      performed by the senior author (B.G.) and had at least 11 months of follow-up.
      The study population included three groups: migraine surgery success,
      improvement, and failure. Thirty-six unique data points were collected for each
      patient. RESULTS: A total of 169 patients met inclusion criteria. Of these, 66
      patients comprised the migraine surgery success group (S, complete elimination of
      migraine headaches); 67 comprised the migraine surgery improvement group (I, >50
      percent reduction in migraine frequency, intensity, or duration); and 36
      comprised the migraine surgery failure group (F, <50 percent reduction in
      migraine frequency, intensity, or duration). Significant differences among the
      groups included age at surgery (S>I, p=0.02), migraine frequency (S<I, p=0.02),
      age of migraine onset (S>I, p=0.003; S>F, p=0.04), history of head or neck injury
      (S<I, p=0.04), daily use of over-the-counter migraine medications (S<I, p=0.05),
      visual symptoms (S>I, p=0.02), increased intraoperative bleeding (S<F, p=0.04;
      I<F, p=0.04), site I (S>F, p=0.0006; I>F, p=0.0004), site II (S>F, p=0.015),
      single operative site (S<F, p=0.005), one to two operative sites (S<F, p=0.04;
      I<F, p=0.01), and four operative sites (S>I, p=0.05; S>F, p=0.04). CONCLUSIONS:
      Factors associated with migraine surgery failure include increased intraoperative
      bleeding and surgery on fewer trigger sites. Factors associated with migraine
      surgery success are older age of migraine onset, higher rate of visual symptoms
      versus improvement group, surgery at site I or II, and deactivating all four
      operative sites. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 21738088
TI  - An anatomical study on the position of the summit of the zygoma:  theoretical
      bases for reduction malarplasty.
AB  - BACKGROUND: To achieve optimal outcomes in reduction malarplasty, the area of
      zygoma from which volume should be reduced must be accurately identified. This
      anatomical study aims to evaluate the location of the zygoma region that
      contributes most to the protrusion of the cheek. METHODS: The morphology of the
      zygoma was studied on 121 Japanese adults (73 men and 48 women). The midpoint of
      the inferior orbital rim, zygomaticomaxillary junction, the junction between the
      frontal process and the zygomatic arch, and the lateral orbital rim were marked
      to be used as anatomical reference points. Then, a vertical plane intersecting
      the anterior and posterior edges of the zygoma was marked. The point of the
      zygoma most distant from the plane was defined as the summit of the zygoma. Three
      dimensional measurement using graphic software was performed, and the positional
      relationships between the summit and the four reference points were evaluated.
      RESULTS: In terms of horizontal position, the summit is located lateral to the
      lateral orbital rim and medial to the junction between the frontal process and
      the zygomatic arch. Regarding vertical position, the summit exists at higher
      positions in men than in women. CONCLUSIONS: The summit of the zygoma is located
      medial to the junction of the frontal process and zygomatic arch. Therefore, bone
      incision lines should be placed medial to the posterior edge of the frontal
      process in reduction malarplasty; effective correction of the protrusion cannot
      be achieved solely by detachment of the zygomatic arch. The summit is located
      higher for men than for women. Therefore, bone incision lines should be placed
      higher for men than for women.

PMID- 21738089
TI  - Intraocular pharmacokinetics after a single intravitreal injection of 1.5 mg
      versus 3.0 mg of bevacizumab in humans.
AB  - PURPOSE: To compare the concentration of unbound bevacizumab in the anterior
      chamber of patients with macular edema, who received a single intravitreal
      injection of two different dosages. METHODS: This was a comparative,
      interventional case series. Twenty-nine nonvitrectomized eyes of 29 patients with
      significant lens opacities and concurrent macular edema were included in the
      study. All patients were treated by a single dose of intravitreal injection of
      bevacizumab 1.5 mg (Group A, n = 13) or 3.0 mg (Group B, n = 16). Subsequent
      phacoemulsification and aspiration of an aqueous humor samples were performed at
      various intervals (1-60 days). The axial length of the globe was measured using
      the IOLMaster to calculate the total volume and corresponding globe size
      corrected half-time. The concentration of unbound bevacizumab was measured by
      enzyme-linked immunosorbent assay and pharmacokinetic parameters including half
      time of elimination. RESULTS: The mean peak concentration was observed in both
      groups on the first day after intravitreal bevacizumab injection. The mean
      concentration of unbound bevacizumab ranged in Group A from 17.5 MUg/mL at
      baseline to 0.66 MUg/mL at Day 57 and in Group B from 28.3 MUg/mL at baseline to
      0.00 MUg/mL at 54 days. The axial lengths of all injected eyes were not
      significantly different between Group A (mean values, 23.026 mm, SD 1.21) and
      Group B (mean, 23.313 mm, SD 1.00; P = 0.31). Regression analysis determined
      elimination half-time values of 7.85 days (R2 = 0.75) in Group A and 11.67 days
      (R2 = 0.91) in Group B. Similar half-times were calculated for globe size
      corrected concentrations with 8.21 days (R2 = 0.81) in Group A and 11.17 days (R2
      = 0.88) in Group B. CONCLUSION: Single- and double-dose injections have similar
      pharmacokinetic characteristics in a first-order exponential decay function. The
      globe size-corrected concentration and half-time did not affect the calculated
      half-time in both groups. Doubled dosing induced a higher peak concentration at
      baseline, but the presumed extended biologic active concentration was no longer
      statistically significant after 6 weeks. The application of twice the dosage does
      not double the duration of its efficacy; it rather appears to extend the
      pharmacological duration by 1 half-time or approximately 8 days to 11 days.

PMID- 21738090
TI  - Intra-arterial indocyanine green angiography in the management of spinal
      arteriovenous fistulae: technical case reports.
AB  - STUDY DESIGN: We first present 2 cases of spinal arteriovenous fistulae (AVFs)
      successfully treated with the help of intra-arterial indocyanine green (ICG)
      angiography. OBJECTIVE: To demonstrate the efficacy of intra-arterial ICG
      angiography in spinal AVFs compared with the role of intravenous ICG injection
      and intraoperative digital subtraction angiography (DSA). SUMMARY OF BACKGROUND
      DATA: Intravenous ICG fluorescent angiography is an emerging intraoperative tool
      to recognize vascular anatomy. The technique is quite simple and provides real
      time vascular hemodynamics in the operative field. However, it takes time for the
      ICG to be washed out; therefore, repeat studies are somewhat tedious and time
      consuming, especially in spinal AVFs with multiple shunts/drainer. In this
      setting, intraoperative DSA has still been the standard to confirm the complete
      obliteration, although this has a risk of radiation exposure and renal failure.
      METHODS: Two patients, a 46-year-old man with spinal dural AVF at the
      cervicomedullary junction and a 68-year-old woman with spinal perimedullary AVF
      at the conus medullaris, were surgically treated with the help of intra-arterial
      ICG angiography. RESULTS: We introduced a catheter into the target artery and
      injected 0.05 mg ICG in 2 mL of normal saline in multiple, short intervals. This
      approach enabled us to detect the residual shunt/drainer and confirm complete
      obliteration. With this technique, a tiny amount of ICG was used in the operative
      field to clearly label only the affected vessels. Intraoperative DSA was not
      performed in these cases. CONCLUSION: These cases demonstrate that intra-arterial
      ICG angiography is a powerful tool for visualizing spinal AVFs in terms of
      addressing the disadvantages of intravenous ICG injection and intraoperative DSA.

PMID- 21738091
TI  - Adhesive arachnoiditis with extensive syringomyelia and giant arachnoid cyst
      after spinal and epidural anesthesia: a case report.
AB  - STUDY DESIGN: A case report of a patient with adhesive arachnoiditis after
      combined spinal and epidural anesthesia. OBJECTIVE: To report an extremely rare
      case of paraplegia due to adhesive arachnoiditis with extensive syringomyelia
      (ES) and a giant anterior arachnoid spinal cyst (AASC) after spinal and epidural
      anesthesia for obstetric surgery. SUMMARY OF BACKGROUND DATA: Progressive
      inflammation of the arachnoid mater due to trauma, infection, or hydrocortisone
      was reported as early as the 1970s. However, coexistence of ES and a giant AASC
      after spinal and epidural anesthesia is extremely rare. METHODS: A 29-year-old
      woman suffered from sudden anuresis 5 months after spinal and epidural anesthesia
      for a cesarean section and subsequently experienced paraplegia and numbness below
      the chest. Magnetic resonance imaging showed an AASC compressing the spinal cord
      at T1-T6 and an adhesive lesion at T7. Posterior laminectomy at T6-T7 and
      adhesiolysis for arachnoid adhesion at T7 were performed. Although there was
      slight recovery of locomotive function postoperatively, it gradually worsened
      until 3 years after surgery. Magnetic resonance imaging at that time demonstrated
      a giant AASC and ES at the lower-thoracic cord. The cord compressed by the AASC
      became thinner sagittally. Secondary surgery involving posterior laminectomy at
      T5-T6 and insertion of a cyst-peritoneal shunt into the AASC was performed.
      RESULTS: The patient could walk without a cane 3 years after the shunt operation,
      although numbness and motor weakness of the lower extremities remained. Magnetic
      resonance imaging 3 years after the shunt operation showed a reduction of the
      AASC and decompression of the cord despite no improvement in ES. CONCLUSION: This
      is the first report of a patient with a giant AASC and ES caused by spinal and
      epidural anesthesia. Although the optimal surgical treatment for these conditions
      remains unclear, shunting of the cyst effectively prevented the progression of
      symptoms.

PMID- 21738092
TI  - Calcitonin enhanced lumbar spinal fusion in a New Zealand rabbit model: a study
      with morphologic and molecular analysis.
AB  - STUDY DESIGN: In this study, the effect of calcitonin on lumbar spinal fusion was
      studied in a New Zealand rabbit model. OBJECTIVE: To investigate whether
      calcitonin can enhance lumbar spinal fusion in a New Zealand rabbit model and
      whether calcitonin can enhance expression genes involved in osteogenesis and
      angiogenesis. SUMMARY OF BACKGROUND DATA: Calcitonin is used to treat
      osteoporosis and diseases involving accelerated bone turnover. Studies have shown
      that calcitonin might also promote bone cell proliferation and bone formation,
      suggesting its possible role in promoting spinal fusion, but few data are
      available. METHODS: The effect of calcitonin on lumbar spinal fusion was analyzed
      in 32 New Zealand rabbits. Each rabbit received 2 autologous iliac bone grafts
      (one between L4-L5 without fixation, one between L6-L7 with fixation). Sixteen
      rabbits received calcitonin (calcitonin group, 1 U/kg daily from day 1 to the day
      of sacrifice), whereas the other 16 did not (control). At weeks 1, 2, 4, and 8,
      after examination for spinal fusion with radiography, 4 rabbits from each group
      were sacrificed. Each graft was histologically scored under light microscopy. In
      addition, we analyzed the messenger RNA (mRNA) levels of collagen I (Col I), bone
      morphometric protein 2 (BMP-2), insulinlike growth factor-1 (IGF-1), and vascular
      endothelial growth factor (VEGF), genes known to be involved in osteogenesis and
      angiogenesis, in each graft. RESULTS: With both fixation and without fixation,
      the bone grafts in rabbits receiving calcitonin showed a higher spinal fusion
      rate and higher histologic scores from week 2 to week 8, and had higher mRNA
      levels of Col I, BMP-2, IGF-1, and VEGF at all time points except BMP-2 and IGF-1
      at week 1, than grafts in rabbits without receiving calcitonin. CONCLUSION:
      Calcitonin can enhance lumbar spinal fusion. One mechanism might be through
      upregulating genes involved in osteogenesis and angiogenesis.

PMID- 21738093
TI  - A prospective randomized FDA-IDE trial comparing Cortoss with PMMA for
      vertebroplasty: a comparative effectiveness research study with 24-month follow
      up.
AB  - STUDY DESIGN: Randomized, controlled, prospective (AAOS therapeutic level I)
      trial conducted under Food and Drug Administration Investigational Device
      Exemption hypothesized noninferiority of a novel bioactive composite material to
      polymethylmethacrylate (PMMA). OBJECTIVE: To determine the safety and efficacy of
      a new, nonresorbable bioactive composite (Cortoss) compared with PMMA, the
      standard treatment of vertebral compression fractures (VCFs). SUMMARY OF
      BACKGROUND DATA: Vertebroplasty with PMMA, the widely adopted treatment for VCFs
      nonresponsive to conservative care, provides effective, immediate pain relief,
      but the material has received criticism for its properties. A new bioactive
      composite material designed specifically for vertebroplasty showed promising
      results in animals and nonrandomized clinical studies and was subsequently
      compared with PMMA in a randomized study. This study represents the first
      prospective study evaluating vertebroplasty comparing PMMA with another material
      with 24-month follow-up. METHODS: Using 2:1 randomization, vertebroplasty was
      performed with Cortoss on 162 patients and PMMA on 94 patients. Inclusion
      criteria were painful osteoporotic VCFs with a visual analogue scale pain score
      of at least 50 mm on a 100-mm scale and at least 30% disability as measured by
      the Oswestry Disability Index. Evaluations at pretreatment, treatment day, and 7
      posttreatment intervals out to 24 months included pain, disability, neurological
      status, adverse events, quality of life, patient satisfaction, analgesic use, and
      independently reviewed radiographs. RESULTS: Noninferiority of Cortoss relative
      to PMMA was observed, with Cortoss-treated patients experiencing significant pain
      relief at 3 months (P = 0.0395) and better maintenance or improvement in function
      at 24 months (P = 0.0299). Incidence of serious device-related adverse events was
      4.3% in both groups; none were life threatening. CONCLUSION: Vertebroplasty using
      either Cortoss or PMMA provides effective, immediate, and lasting pain relief and
      prevents further loss of function. Both materials performed comparably at most
      time points; Cortoss demonstrated better results for pain reduction at 3 months
      and for function at 24 months.

PMID- 21738095
TI  - Implementation of a guideline for low back pain management in primary care: a
      cost-effectiveness analysis.
AB  - STUDY DESIGN: Cost-effectiveness analysis alongside a cluster randomized
      controlled trial. OBJECTIVE: To study the cost-effectiveness of 2 low back pain
      guideline implementation (GI) strategies. SUMMARY OF BACKGROUND DATA: Several
      evidence-based guidelines on management of low back pain have been published.
      However, there is still no consensus on the effective implementation strategy.
      Especially studies on the economic impact of different implementation strategies
      are lacking. METHODS: This analysis was performed alongside a cluster randomized
      controlled trial on the effectiveness of 2 GI strategies (physician education
      alone [GI] or physician education in combination with motivational counseling
      [MC] by practice nurses)--both compared with the postal dissemination of the
      guideline (control group, C). Sociodemographic data, pain characteristics, and
      cost data were collected by interview at baseline and after 6 and 12 months. low
      back pain-related health care costs were valued for 2004 from the societal
      perspective. RESULTS: For the cost analysis, 1322 patients from 126 general
      practices were included. Both interventions showed lower direct and indirect
      costs as well as better patient outcomes during follow-up compared with controls.
      In addition, both intervention arms showed superiority of cost-effectiveness to
      C. The effects attenuated when adjusting for differences of health care
      utilization prior to patient recruitment and for clustering of data. CONCLUSION:
      Trends in cost-effectiveness are visible but need to be confirmed in future
      studies. Researchers performing cost-evaluation studies should test for baseline
      imbalances of health care utilization data instead of judging on the
      randomization success by reviewing non-cost parameters like clinical data alone.

PMID- 21738096
TI  - Growing rod fractures: risk factors and opportunities for prevention.
AB  - STUDY DESIGN: Review of a prospectively collected growing rod database.
      OBJECTIVE: To define risk factors for and characterize the nature of growing rod
      fractures. SUMMARY OF BACKGROUND DATA: Rod fracture is a common complication of
      growing rod treatment. The project sought to analyze risk factors for rod
      breakage and develop preventive strategies. METHODS: Records of 327 patients in a
      prospectively collected growing rod database were studied. Risk factors studied
      were studied as patient-related and rod-related. Multivariate analysis was
      performed. RESULTS: Eighty-six rod fractures occurred in 49 patients (49 of 327,
      15%). Sixteen patients had repeat fractures with eight patients having more than
      two fractures (maximum six). The most common fracture locations were above or
      below the tandem connectors (34 of 86) and near the thoracolumbar junction (35 of
      86). Other locations were adjacent to anchors (12 of 86) and cross-links (2 of
      86). Syndromic diagnoses had the highest rate of fracture; significantly greater
      than neuromuscular diagnoses (14% vs. 2%, P = 0.01). Patients who were ambulatory
      had a higher fracture rate (21% vs. 8.7%, P = 0.01). Single rods had a higher
      fracture rate than dual rods (36% vs. 11%, P < 0.001). Repeat fracture was also
      more common in patients with single rods (13% vs. 2%, P = 0.0002). In dual-rod
      constructs, the incidence of both rods breaking at the same time was 26% (7 of
      27). Stainless steel rods had a higher fracture rate than titanium rods (29% vs.
      18%, P = 0.02). The nonfracture group had larger diameter rods than the fracture
      group (P = 0.01). The fracture group had shorter tandem connectors than the
      nonfracture group (P < 0.001). Neither the size of preoperative scoliosis (P =
      0.2) nor kyphosis (P = 0.4) was a risk factor for fracture. Length of
      instrumentation (P = 0.9), anchor type (P = 0.6), and pelvic fixation (P = 0.38)
      had no significant effect on fracture rates. Eight wound complications were
      reported, including three cases of skin breakdown at the rod fracture site.
      CONCLUSION: Risk factors for rod fractures include prior fracture, single rods,
      stainless steel rods, small diameter rods, proximity to tandem connectors, short
      tandem connectors, and preoperative ambulation. Repeat fractures are common,
      especially with single rods. Rod replacement, with larger diameter rods if
      appropriate, may be a preferred strategy over connecting the broken rods as
      fractures signal fatigue of the rod.

PMID- 21738098
TI  - Costs and cost-effectiveness of spinal cord stimulation (SCS) for failed back
      surgery syndrome: an observational study in a workers' compensation population.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: We estimated the cost
      effectiveness of spinal cord stimulation (SCS) among workers' compensation
      recipients with failed back surgery syndrome (FBSS). SUMMARY OF BACKGROUND DATA:
      Randomized controlled trial (RCT) evidence suggests that SCS is more effective at
      6 months than medical management for patients with FBSS. However, procedure costs
      are high and workers' compensation claimants often have worse outcomes than other
      patients. METHODS: We enrolled 158 FBSS patients receiving workers' compensation
      into three treatment groups: trial SCS with or without permanent device implant
      (n = 51), pain clinic (PC) evaluation with or without treatment (n = 39), and
      usual care (UC; n = 68). The primary outcome was a composite measure of pain,
      disability and opioid medication use. As reported previously, 5% of SCS patients,
      3% of PC patients and 10% of UC patients achieved the primary outcome at 24
      months. Using cost data from administrative databases, we calculated the cost
      effectiveness of SCS, adjusting for baseline covariates. RESULTS: Mean medical
      cost per SCS patient over 24 months was $52,091. This was $17,291 (95% confidence
      intervals [CI], $4100-30,490) higher than in the PC group and $28,128 ($17,620
      38,630) higher than in the UC group. Adjusting for baseline covariates, the mean
      total medical and productivity loss costs per patient of the SCS group were
      $20,074 ($3840-35,990) higher than those of the PC group and $29,358 ($16,070
      43,790) higher than those of the UC group. SCS was very unlikely (<5%
      probability) to be the most cost-effective intervention. CONCLUSION: In this
      sample of workers' compensation recipients, the high procedure cost of SCS was
      not counterbalanced by lower costs of subsequent care, and SCS was not cost
      effective. The benefits and potential cost savings reported in RCTs may not be
      replicated in workers' compensation patients treated in community settings.

PMID- 21738099
TI  - The contribution of an electronic conductivity device to the safety of pedicle
      screw insertion in scoliosis surgery.
AB  - STUDY DESIGN: Retrospective, controlled clinical study. OBJECTIVE: To evaluate
      the contribution of an electronic conductivity device (ECD) to the safety of
      pedicle screw insertion in pediatric scoliosis surgery. SUMMARY OF BACKGROUND
      DATA: The implantation of pedicle screws in spinal deformity correction surgery
      has evolved into the currently predominant fixation technique. Methodologies for
      optimizing placement of pedicle screws are fluoroscopy, electromyography, and
      intraoperative image-based navigation. A hand-held ECD was recently introduced.
      METHODS: Pedicle screw insertion was analyzed in 248 pediatric scoliosis patients
      (idiopathic, congenital, neuromuscular, syndromatic). Group I included 150
      procedures without the aid of the ECD and group II included 98 ECD-aided
      procedures. The two groups were matched by age, sex, etiology, Cobb angle, and
      surgical criteria. Data on screw position and concomitant neuromonitoring alarms
      were compared. Group I consisted of patients operated with both the hybrid
      construct and pedicle screw instrumentation, while group II consisted of patients
      operated solely with pedicle screws. Both groups were operated on by a single
      surgeon with the same neurophysiologic methodology. Clinically relevant misplaced
      pedicle screws were established by intraoperative monitoring alarms concomitant
      with pedicle screw insertion. RESULTS: A total of 1270 pedicle screw placements
      were analyzed in group I and compared with 1400 pedicle screw placements in group
      II. Neuromonitoring alarms concomitant with screw placement occurred in 10
      procedures in group I (6.6%) compared with 3 in group II (3.0%). The contribution
      of the electronic device to reducing the number of neurophysiologic alarms was
      significant (P = 0.048, Fisher exact test). Nine of the 13 monitoring alarms
      (69%) were associated with implantation adjacent to the apex of the spinal curve.
      CONCLUSION: The use of an ECD significantly reduced the incidence of clinically
      relevant misplaced screws in a variety of scoliosis patients, thereby increasing
      the safety of pedicle screw implantation.

PMID- 21738100
TI  - Intraoperative waste in spine surgery: incidence, cost, and effectiveness of an
      educational program.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: This study aims to
      quantify the incidence of intraoperative waste in spine surgery and to examine
      the efficacy of an educational program directed at surgeons to induce a reduction
      in the intraoperative waste. SUMMARY OF BACKGROUND DATA: Spine procedures are
      associated with high costs. Implants are a main contributor of these costs.
      Intraoperative waste further exacerbates the high cost of surgery. METHODS: Data
      were collected during a 25-month period from one academic medical center (15
      month observational period, 10-month post-awareness program). The total number of
      spine procedures and the incidence of intraoperative waste were recorded
      prospectively. Other variables recorded included the type of product wasted, cost
      associated with the product or implant wasted, and reason for the waste. RESULTS:
      Intraoperative waste occurred in 20.2% of the procedures prior to the educational
      program and in 10.3% of the procedures after the implementation of the program (P
      < 0.0001). Monthly costs associated with surgical waste were, on average, $17680
      prior to the awareness intervention and $5876 afterwards (P = 0.0006). Prior to
      the intervention, surgical waste represented 4.3% of total operative spine
      budget. After the awareness program this proportion decrease to an average of
      1.2% (P = 0.003). CONCLUSION: Intraoperative waste in spine surgery exacerbates
      the already costly procedures. Extrapolation of this data to the national level
      leads to an annual estimate of $126,722,000 attributable to intraoperative spine
      waste. A simple educational program proved to be and continues to be effective in
      making surgeons aware of the import of their choices and the costs related to
      surgical waste.

PMID- 21738101
TI  - Pediatric pedicle screw placement using intraoperative computed tomography and 3
      dimensional image-guided navigation.
AB  - STUDY DESIGN: A retrospective cohort study reporting the use of intraoperative
      computed tomography (CT) and image-guided navigation system for the placement of
      pedicle screws in pediatric compared with adult patients. OBJECTIVE: To evaluate
      the accuracy of open pedicle screw placement in pediatric patients using
      intraoperative CT and 3-dimensional (3D) image-guided navigation. SUMMARY OF
      BACKGROUND DATA: Pedicle screws are widely used in children for the correction of
      spinal deformity. Navigation systems and intraoperative CT are now available as
      an adjunct to fluoroscopy and anatomic techniques for placing pedicle screws and
      verifying screw position. METHODS: From 2007 to 2010, 984 pedicle screws were
      placed in a consecutive series cohort of 50 pediatric patients for spinal
      deformity correction with the use of intraoperative CT (O-arm, Medtronic, Inc,
      Louisville, CO) and a computerized navigation system (Stealth, Medtronic, Inc,
      Louisville, CO). The primary outcome measure for this study is redirection or
      removal of screw on the basis of the intraoperative CT imaging. During the study
      period, 1511 screws were placed in adult patients using the same image guidance
      system. RESULTS: A total of 984 pedicle screws were implanted using real-time
      navigation, with a mean of 20 screws per patient (range: 2-34). On the basis of
      intraoperative CT, 35 screws (3.6%) were revised (27 redirected and 8 removed),
      representing a 96.4% accuracy rate. No patients returned to the operating room
      because of screw malposition.Of the 1511 screws placed in adult patients, 28
      (1.8%) were revised intraoperatively for malposition on CT imaging, for an
      overall 98.2% accuracy rate. Screw revision thus was more common in the pediatric
      population (P = 0.008). However, the pediatric screw accuracy rate is
      significantly higher than the findings from a recent meta-analysis of
      predominantly nonnavigated screws in children, reporting a 94.9% accuracy rate (P
      = 0.03). CONCLUSION: We report 96.4% accuracy in pediatric pedicle screw
      placement using intraoperative CT and a 3D navigation system. This is similar to
      other reports and has better accuracy than a recent meta-analysis of nonnavigated
      screws in children.

PMID- 21738102
TI  - Six-month mortality and cardiac catheterization in non-ST-segment elevation
      myocardial infarction patients with anemia.
AB  - BACKGROUND: It is unknown how anemia influences the invasive management of
      patients with non-ST-segment elevation myocardial infarction (NSTEMI) and
      associated mortality. We investigated whether receipt of cardiac catheterization
      relates to 6-month death rates among patients with different severity of anemia.
      METHODS: We used data from the population-based Worcester Heart Attack Study,
      which included 2634 patients hospitalized with confirmed NSTEMI, from three
      percutaneous coronary intervention-capable medical centers in the Worcester
      (Massachusetts, U.S.A.) metropolitan area, during five biennial periods between
      1997 and 2005. Severity of anemia was categorized using admission hematocrit
      levels: less than or equal to 30.0% (moderate-to-severe anemia), 30.1-39.0% (mild
      anemia), and more than 39.0% (no anemia). Propensity matching and conditional
      logistic regression adjusting for hospital use of aspirin, heparin, and plavix
      compared 6-month postadmission all-cause mortality rates in relation to cardiac
      catheterization during NSTEMI hospitalization. RESULTS: Compared with patients
      without anemia, patients with anemia were less likely to undergo cardiac
      catheterization {adjusted odds ratio (AOR) 0.79 [95% confidence interval (CI):
      0.67-0.95] for mild anemia and 0.45 (95% CI: 0.42-0.49) for moderate-to-severe
      anemia}. After propensity matching, cardiac catheterization was associated with
      lower 6-month death rates only in patients without anemia [AOR 0.26 (95% CI: 0.09
      0.79)] but not in patients with mild anemia [AOR 0.55 (95% CI: 0.25-1.23)]. The
      small number of patients rendered data inconclusive for patients with moderate-to
      severe anemia. CONCLUSION: Anemia at the time of hospitalization for NSTEMI was
      associated with lower utilization of cardiac catheterization. However, cardiac
      catheterization use was associated with a decreased risk of dying at 6 months
      after hospital admission only in patients without anemia.

PMID- 21738103
TI  - Keratitis in reactive arthritis (Reiter syndrome) in childhood.
AB  - PURPOSE: To present a rare ocular manifestation of reactive arthritis (Reiter
      syndrome) in a child. METHODS: A 10-year-old girl who was admitted to our
      hospital with low-grade fever, arthritis, and aching left eye with blurred vision
      was diagnosed with Reiter reactive arthritis. At the time of admittance, the
      ophthalmologic examination revealed keratitis; this mildly affected the vision.
      RESULTS: Keratitis resolved under treatment with topical steroids and antibiotic
      drops after 1 month, without scarring. Although 75% of the patients with reactive
      arthritis present ophthalmic manifestations, keratitis is a very rare finding in
      reactive arthritis and even rarer in children. CONCLUSIONS: It should be kept in
      mind that keratitis could be an ocular manifestation of reactive arthritis in
      young patients.

PMID- 21738104
TI  - A phase II study of gefitinib in patients with metastatic melanoma.
AB  - Gefitinib is an inhibitor of the epidermal growth factor receptor, which is
      frequently expressed on both choroidal and nonchoroidal melanoma cells. We
      evaluated the clinical efficacy of gefitinib in patients with metastatic
      melanoma. Patients with stage IV or unresectable stage III melanoma and Zubrod
      performance status of less than or equal to 2 were eligible. Previous systemic
      treatment for metastatic disease was required. The dose of oral gefitinib was 250
      mg administered daily, and tumor response was evaluated every 6 weeks. Forty-six
      patients with nonchoroidal melanoma and six with choroidal melanoma were treated,
      and 48 were evaluable for response. The median age was 62.5 years. Forty-one
      patients (79%) had stage M1c disease. There were no drug-related grade 4 or 5
      adverse events, and fatigue was the only grade 3 adverse event that occurred in
      more than 5% of patients. Two patients (4%) had partial responses and 13 patients
      (27%) had disease stabilization. The two responders had a median duration of
      response of 10.9 months. The median overall progression-free survival was 1.4
      months and the median overall survival was 9.7 months. Among the patients with
      sufficient tissues obtained before and 6 weeks after starting gefitinib
      administration, there were no notable trends in the changes of the tumoral
      expression of p-ERK1/2, p-AKT, PAK1, and serum levels of vascular endothelial
      growth factor or IL-8 with treatment. We concluded that gefitinib was well
      tolerated but had minimal clinical efficacy as a single-agent therapy for
      unselected patients with metastatic melanoma.

PMID- 21738105
TI  - Use of novel cardanol-porphyrin hybrids and their TiO2-based composites for the
      photodegradation of 4-nitrophenol in water.
AB  - Cardanol, a well known hazardous byproduct of the cashew industry, has been used
      as starting material for the synthesis of useful differently substituted
      "cardanol-based" porphyrins and their zinc(II), copper(II), cobalt(II) and
      Fe(III) complexes. Novel composites prepared by impregnation of polycrystalline
      TiO2 powder with an opportune amount of "cardanol-based" porphyrins, which act as
      sensitizers for the improvement of the photo-catalytic activity of the bare TiO2,
      have been used in the photodegradation in water of 4-nitrophenol (4-NP), which is
      a toxic and bio-refractory pollutant, dangerous for ecosystems and human health.

PMID- 21738106
TI  - Design, synthesis and biological activity evaluation of arylpiperazine
      derivatives for the treatment of neuropathic pain.
AB  - In this work, a series of arylpiperazine derivatives were synthesized and
      screened by in vivo pharmacological trials. Among the tested compounds, 2-(4-(3
      (trifluoromethyl)phenyl)piperazin-1-yl)-1-phenylethanone (18) and 2-(4-(2,3
      dimethylphenyl)piperazin-1-yl)-1-phenylethanone (19) exhibited potent analgesic
      activities in both the mice writhing and mice hot plate tests. They showed more
      than 70% inhibition relative to controls in the writhing test, and increased
      latency by 116.0% and 134.4%, respectively, in the hot plate test. Furthermore,
      compound 18 was also active in the models of formalin pain and neuropathic pain
      without sedative side effects.

PMID- 21738107
TI  - Vilazodone (Viibryd)--a new antidepressant.
AB  - Vilazodone (Viibryd--Forest), a selective serotonin reuptake inhibitor (SSRI) and
      partial 5-HT(1A) receptor agonist, has been approved by the FDA for treatment of
      depression. It has been claimed to have no sexual side effects and not to cause
      weight gain.

PMID- 21738108
TI  - Testosterone topical solution (Axiron) for hypogonadism.
AB  - The Medical Letter recently reviewed a topical gel formulation of testosterone
      (Fortesta) for treatment of hypogonadism in men. A topical testosterone
      replacement product for application to the axilla, Axiron (Lilly) solution, has
      now become available for the same indication. This site of application presumably
      minimizes the risk of transferring the drug to a family member or sexual partner.

PMID- 21738109
TI  - Levofloxacin revisited.

PMID- 21738110
TI  - Bone metastases, 2011: an old and new field of interest for diagnostic and
      therapeutic nuclear medicine.

PMID- 21738111
TI  - Bone metastases, general and clinical issues.
AB  - The skeleton is the most common organ for metastasis from solid tumours. Bone
      metastases pose significant diagnostic and clinical challenges and represent an
      important cause of cancer-related morbidity. Without appropriate bone-directed
      therapy, many patients will be at high risk for potentially debilitating skeletal
      related events (SREs), such as pain, bone fractures, neurologic deficits and
      hypercalcemia, severely impacting on the patient's quality of life. Because of
      their high incidence, bone metastases impose significant demands on health care
      resources. The optimal management of skeletal metastases depends on the
      underlying biology of the disease, the extent of bone involvement, the presence
      and severity of symptoms, the availability of effective systemic therapies and
      life expectancy of the patient. This article discusses clinical issues concerning
      diagnosis and available treatment approaches based on the presentation of
      skeletal involvement. Emphasis is placed on the role of external beam
      radiotherapy as a local mode of treatment for palliation of bone pain,
      decompression of epidural compression and as potential ablative approach through
      high-dose image-guided irradiation (IGRT) in patients presenting with
      oligometastatic disease.

PMID- 21738112
TI  - Pathophysiological premises to radiotracers for bone metastases.
AB  - Aim of our paper is to review the most important radio-compounds that can be
      successfully used to detect and/or characterize bone metastases. From a didactic
      point of view, we made a distinction between two main categories , the first
      allowing to individuate bone's reaction (osteotropic agents), the second trying
      to detect metastatic tumor cells (oncotropic agents). A wide description of the
      most diffuse Tc-99m diphosphonates , including analysis of uptake mechanisms and
      pharmacokinetics, is followed by a brief report on pathophysiological premises to
      the clinical use of F-18 fluoride and of specific (radioiodine, radiolabeled
      somatostatin or cathecolamine analogues) or non specific, as Tc-99m sestamibi, F
      18 fluorodeoxhyglucose, F-18 choline, F-18 thymidine) oncotropic agents. At the
      end, the possibility to use diagnostic radiotracers to act both in recruiting
      patients with bone metastases undergoing radionuclide therapy and for their
      dosimetric evaluation is also discussed.

PMID- 21738113
TI  - Diagnosis of bone metastasis: recent comparative studies of imaging modalities.
AB  - Various imaging modalities are currently available to diagnose bone metastasis.
      The two main anatomical modalities are computed tomography (CT) and magnetic
      resonance imaging (MRI), with many variants proposed for the MRI procedure,
      including diffusion-weighted imaging. The two main functional modalities are
      scintigraphy and PET, also with many variants in the radiopharmaceutical, from
      the "all purpose" 99mTc labelled bisphosphonates to very selective
      radiopharmaceuticals for rare neoplasia. The diagnostic strategy will become more
      and more individually tailored according to the patient's clinical and biological
      data (primary cancer type, phase of the evolution, markers of aggressiveness,
      serum levels of biological tracers of bone metabolism, circulating or
      disseminating tumour cells ...). If imaging is indicated, the diagnostic strategy
      will also depend on the availability and the diagnostic performance of the
      imaging modalities. Assessment of diagnostic performance requires comparative
      studies, performed with an adequate methodology. The main methodological
      weaknesses encountered in studies intending to compare imaging modalities for
      diagnosing bone metastasis are summarised. Comparative studies have been
      reviewed, which address the initial diagnosis of skeletal metastases in solid
      tumours except primary bone cancers. The results of more than 140 such
      comparative studies are then summarised and briefly commented, according to the
      type of the primary cancer, and according to the compared imaging modalities.

PMID- 21738114
TI  - State of the art of palliative therapy.
AB  - Bone pain in advanced stages of cancer significantly decreases the patient's
      quality of life having a great impact on physical, physiological and social
      functioning. About 65% of patients with prostate or breast cancer will experience
      symptomatic skeletal metastases. Bone pain sustained by osseous metastases
      represents the most frequent kind of pain and its clinical presentation and
      characteristics differ from other type of neoplastic pain (i.e., neuropathic or
      visceral ones). Pathophysiology of bone pain is not yet completely understood but
      a general mechanism including infiltration of bone tissue associated with
      osteolysis and release of biological active molecules able to stimulate
      peripheral nervous terminals, seems to be principally involved. In oncological
      practice, painful skeletal metastases are managed by different multidisciplinary
      modalities which include the use of systemic analgesics (i.e., bisphosphonates),
      antineoplastic agents (i.e., hormones and chemotherapeutics), external beam
      radiotherapy, interventional radiology and radiopharmaceuticals. In this review
      we will discuss the state of the art of palliative therapy of bone pain with
      particular emphasis to the current approved radiopharmaceuticals, focusing on
      indications, patient selection, efficacy and toxicity. Some remarks on new or
      under developing strategies in systemic metabolic radiopharmaceutical therapy
      will be reported.

PMID- 21738115
TI  - The Vienna protocol and perspectives in radionuclide therapy.
AB  - The Vienna protocol for [153]Sm-EDTMP-therapy is based on the experience of the
      last two decades. Repeated treatments at a low dose are applied by several
      authors in order to achieve the maximum therapeutic effect with the lowest
      haematological toxicity. Significant benefits on pain palliation and some
      regression are documented. In contrast to earlier claims, [153]Sm-EDTMP treatment
      should be started as soon as more than 1 bone lesion appears in bone scintigraphy
      and/or bone pain becomes evident. Prospective randomized controlled studies,
      however, are urgently warranted in order to assess benefits beyond bone pain
      palliation on an evidence base. The combination with chemotherapy as well as
      radiotherapy may further improve the clinical results. Further research should be
      directed to identify underlying mechanisms of response and predictors of benefit
      and to elaborate an improved therapeutic schedule for further enhancing the
      response rate.

PMID- 21738116
TI  - Radionuclide therapy and integrated protocols for bone metastases.
AB  - Bone metastases are responsible for most of the morbidity and mortality
      associated with solid malignant tumors, occurring in about 65-70% of the patients
      with advanced breast or prostate cancer. The pathophysiology of skeletal
      metastasis is a complex process that involves several biologic process leading to
      cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with
      the mediation of several factors including cytokines, serine proteases and tumor
      derived factors. The clinical management of pain from bone metastasis, which is
      mostly due to indirect stimulation of sensory nerve endings by cytokines and
      other biologically-active compounds released locally in response to the presence
      of tumor cells in the bone marrow, includes several options that can be used
      either alone or in varying combinations, such as analgesic drugs, chemo- or
      hormonal therapy, bisphosponates, external beam radiation therapy, and surgery.
      Bone-seeking radiopharmaceuticals play an important role in the treatment of pain
      caused by multiple blastic or mixed-type skeletal lesions; they have in general a
      favorable toxicity profile and a high rate of overall clinical benefit, although
      they may differ in terms of duration of pain palliation and suitability for
      repeat treatments. The palliative effect can be attributed to the radiation
      targeted to the bone marrow space, and the overall average response ranges
      between about 45-80%, with complete response in 10-30% of the cases. In selected
      clinical conditions, radionuclide therapy can also constitute an effective
      systemic treatment beyond bone pain palliation, and a synergistic anti-tumour
      effect can be expected by the combination with other agents, such as chemotherapy
      or bisphosphonates. This review summarizes the current experience with bone
      seeking radiopharmaceuticals used for bone pain palliation, focusing on
      indications, patients' selection, efficacy and toxicity. Finally, the available
      data on combination therapies showing encouraging results as to potential anti
      tumor efficacy are also reviewed.

PMID- 21738117
TI  - Fluorocholine (18F) and sodium fluoride (18F) PET/CT in the detection of prostate
      cancer: prospective comparison of diagnostic performance determined by masked
      reading.
AB  - AIM: The aim of this paper was to compare the diagnostic performance of positron
      emission tomography/computed tomography (PET/CT) with fluorocholine (18F) (FCH)
      or fluoride(18F) (FNa) for the detection of bone metastasis in patients with
      prostate cancer complaining from osteoarticular pain, taking into account whether
      they were referred for initial staging or recurrence localization. The initial
      hypothesis was that FCH site-based specificity would be superior to that of F Na,
      with no loss in sensitivity. METHODS: Forty-two patients were enrolled in this
      prospective study, underwent both PET/CTs and were then followed-up for at least
      6 months. The standard of truth (SOT) about the presence/absence and location of
      bone metastasis could be determined in 40 patients, by 2 independent medical
      assessors, blinded to the results of both PET/CTs. The comparison was performed
      according to the guideline of the European Medicines Agency, i.e. based on the
      results of blind reading with SOT as reference. RESULTS: Bone extension was
      present in 22 patients and absent in 18. Patient-based performance for FCH vs.
      FNa was 91% vs. 91% for sensitivity, 89% vs. 83% for specificity and 90% vs. 88%
      for accuracy (no significant difference). Of 360 skeletal sites, 68 were
      malignant and 292 non-invaded. There was no significant difference in site-based
      performance in the group of patients referred at initial staging, but in the
      group of patients referred for suspicion of recurrence, FCH was significantly
      more specific than FNa (96% vs. 91%, P=0.033 with Obuchowski's correction) while
      sensitivity was the same, 89%. CONCLUSION: Both radiopharmaceuticals, based on a
      very different metabolic approach, showed good diagnostic performance. If FCH is
      available, it should be preferred in patients after initial treatment.

PMID- 21738118
TI  - Novel treatment options in the management of metastatic breast cancer.
AB  - Few breast cancer patients present with metastatic disease at the initial
      diagnosis. However, approximately one-quarter of patients with lymph node
      negative disease and one half of patients with lymph node-positive tumors will
      ultimately develop distant recurrent breast cancer. Standard treatment of
      metastatic breast cancer generally includes systemic treatment and surgery or
      radiation as needed and when indicated for palliation of localized symptomatic
      metastases. Extending survival and improving quality of life are the primary
      focus of patient management; thus, there is a preference for the use of minimally
      toxic treatments. Taxanes have played a significant role in improving outcomes,
      but many patients still experience disease progression. Many new and emerging
      agents have been developed for metastatic breast cancer, including both biologic
      therapies and chemotherapies. A common theme among these therapies is their
      ability to target specific molecules or processes unique to cancer cells,
      enhancing the potency and reducing many of the toxicities typically observed with
      standard cytotoxic chemotherapies. Such agents include poly(ADP)-ribose
      polymerase inhibitors (iniparib), trastuzumab-DM1, everolimus, the epothilones
      (ixabepilone), and eribulin. Although metastatic breast cancer remains incurable,
      the introduction of new agents and new treatment approaches has led to an
      incremental build-up in terms of survival benefits.

PMID- 21738119
TI  - Recent advances in the treatment of breast cancer: highlights from the 2010 San
      Antonio Breast Cancer Symposium.
AB  - The annual San Antonio Breast Cancer Symposium (SABCS) remains one of the most
      important meetings in the field of breast cancer. SABCS is a forum to present
      relevant information, combining discussions and presentations in the setting of
      basic research, translational research, and clinical cancer research. Many of
      these studies impact patient management and guide the development of new research
      strategies. The 2010 SABCS was very well attended by investigators, clinicians,
      and allied health professionals from multiple countries. Presentations at the
      meeting addressed specific topics, including prevention, management of patients
      in the early and advanced stage settings, and utilization of molecular markers
      for research strategies. There were many areas that disclosed important
      information for clinicians and patients. The abstracts included in this
      supplement concentrate on advancements in the management of breast cancer
      patients with both early-stage and advanced-stage disease.

PMID- 21738120
TI  - Accuracy of pulse oximeter readings from probe placement on newborn wrist and
      ankle.
AB  - OBJECTIVE: To compare the accuracy of pulse oximetry oxygen saturation (SpO(2))
      measured on the wrist compared with the ipsilateral palm, and SpO(2) measured on
      the ankle compared with the ipsilateral sole. STUDY DESIGN: In this prospective
      observational study, neonates admitted to the neonatal intensive care unit were
      enrolled. We recorded SpO(2) (Masimo Radical-7 pulse oximeter) detected at the
      palm and ipsilateral wrist initially, then at 30 s, and at 1 min, and we repeated
      the same procedure over the sole and ipsilateral ankle. We recorded the time to
      obtain the SpO(2) readings from all these sites. Regression analysis was
      performed to determine the relationship between paired SpO(2) measurements. The
      mean difference (bias) and standard deviation of the paired SpO(2) differences
      (precision) were calculated (Bland-Altman plots). RESULT: A total of 150 patients
      (birth weight 2381+/-1020 g, gestational age 34.3+/-4.3 weeks, median postnatal
      age 3.5 days (25th-75th percentile 1-16 days)) were enrolled. There was a good
      correlation between SpO(2) measured at the palm versus the wrist (r=0.95, P<0.001
      (right); r=0.97, P< 0.001 (left)) and between SpO(2) measured at the sole versus
      the ankle (r=0.92, P<0.001 (right); r=0.91, P<0.001 (left)). There was also a
      good agreement between paired SpO(2) measurements from these sites. The bias and
      precision for SpO(2) at the right palm and right wrist was 0.08+/-0.94% and for
      the left palm and left wrist 0.22+/-0.87%. Similarly, the bias and precision for
      SpO(2) at the right sole and right ankle was -0.03+/-0.93% and for the left sole
      and left ankle was -0.01+/-0.93%. CONCLUSION: Our results show that the wrist and
      ankle can be used as alternative sites to measure SpO(2) in newborn infants in
      place of the routinely used palm or sole.

PMID- 21738121
TI  - Severe airway obstruction during surfactant administration using a standardized
      protocol: a prospective, observational study.
AB  - OBJECTIVE: The objective of this study was to evaluate the occurrence of adverse
      effects during surfactant delivery, using a standardized protocol for
      administration and management of complications. STUDY DESIGN: The protocol was
      developed, implemented and used for 6 months. Vital signs and ventilatory
      parameters were prospectively recorded during the procedure. Infants were
      classified into three groups, based on the occurrence and severity of
      complications: no, minor or major. RESULT: A total of 39 infants received
      surfactant and 19 presented some complication: 11 minor and 8 major. Six of the
      major complications were episodes of severe airway obstruction (SAO) and five
      occurred in extreme low birth weight (ELBW) infants that had more severe lung
      disease before surfactant delivery. Two cases of persistent pulmonary
      hypertension occurred in infants with birth weight>1000  g. CONCLUSION: This
      study identified a high rate of SAO and provides data to support changes in the
      protocol, which should include faster and more robust increases in positive
      inspiratory pressures in ELBW infants presenting with SAO.

PMID- 21738122
TI  - Prenatal and perinatal predictors of blood pressure at school age in former
      preterm, low birth weight infants.
AB  - OBJECTIVE: The objective of this study is to investigate prenatal and perinatal
      determinants of school age blood pressure (BP) in former preterm, low birth
      weight infants. STUDY DESIGN: We studied 694 participants in the Infant Health
      and Development Program, an eight-center longitudinal study of children born <=
      37 weeks and <= 2500  g. We obtained information about prenatal and perinatal
      factors by interview and medical record review, and measured BP three times at
      age 6.5 years. RESULT: Adjusting for sex, age, sociodemographic variables and
      height Z-score; for each Z-score birth weight for gestational age-which
      represents fetal growth-systolic BP at 6.5 years was 0.7  mm  Hg higher (95%
      confidence interval -0.1, 1.6). Maternal age, pre-pregnancy weight, gestational
      weight gain, smoking, preeclampsia, gestational diabetes, and child gestational
      age and neonatal complications were also not associated with BP. CONCLUSION: In
      contrast to full-term infants, slower fetal growth was not associated with higher
      BP in former preterm, low birth weight infants.

PMID- 21738123
TI  - Knockout and pullout recombineering for naturally transformable Burkholderia
      thailandensis and Burkholderia pseudomallei.
AB  - Phage lambda-Red proteins are powerful tools for pulling and knocking out
      chromosomal fragments but have been limited to the gamma-proteobacteria.
      Procedures are described here to easily knock out (KO) and pull out (PO)
      chromosomal DNA fragments from naturally transformable Burkholderia thailandensis
      and Burkholderia pseudomallei. This system takes advantage of published compliant
      counterselectable and selectable markers (sacB, pheS, gat and the arabinose
      utilization operon) and lambda-Red mutant proteins. pheS-gat (KO) or oriT
      ColE1ori-gat-ori1600-rep (PO) PCR fragments are generated with flanking 40- to 45
      bp homologies to targeted regions incorporated on PCR primers. One-step
      recombination is achieved by incubation of the PCR product with cells expressing
      lambda-Red proteins and subsequent selection on glyphosate-containing medium.
      This procedure takes ~10 d and is advantageous over previously published
      protocols: (i) smaller PCR products reduce primer numbers and amplification
      steps, (ii) PO fragments suitable for downstream manipulation in Escherichia coli
      are obtained and (iii) chromosomal KO increases flexibility for downstream
      processing.

PMID- 21738124
TI  - Using the Q system in Drosophila melanogaster.
AB  - In Drosophila, the GAL4/UAS/GAL80 repressible binary expression system is widely
      used to manipulate or mark tissues of interest. However, complex biological
      systems often require distinct transgenic manipulations of different cell
      populations. For this purpose, we recently developed the Q system, a second
      repressible binary expression system. We describe here the basic steps for
      performing a variety of Q system experiments in vivo. These include how to
      generate and use Q system reagents to express effector transgenes in tissues of
      interest, how to use the Q system in conjunction with the GAL4 system to generate
      intersectional expression patterns that precisely limit which tissues will be
      experimentally manipulated and how to use the Q system to perform mosaic
      analysis. The protocol described here can be adapted to a wide range of
      experimental designs.

PMID- 21738125
TI  - Volumetric real-time multispectral optoacoustic tomography of biomarkers.
AB  - Multispectral optoacoustic tomography (MSOT) has recently been developed to
      enable visualization of optical contrast and tissue biomarkers, with resolution
      and speed representative of ultrasound. In the implementation described here,
      MSOT enables operation in real-time mode by capturing single cross-sectional
      images in <1 ms from living small animals (e.g., mice) and other tissues of
      similar dimensions. At the core of the method is illumination of the object using
      multiple wavelengths in order to resolve spectrally distinct biomarkers over
      background tissue chromophores. The system allows horizontal placement of a mouse
      in the imaging chamber and three-dimensional scanning of the entire body without
      the need to immerse the mouse in water. Here we provide a detailed description of
      the MSOT scanner components, system calibration, selection of image
      reconstruction algorithms and animal handling. Overall, the entire protocol can
      be completed within 15-30 min for acquisition of a whole-body multispectral data
      set from a living mouse.

PMID- 21738127
TI  - Genetic engineering of human pluripotent cells using TALE nucleases.
AB  - Targeted genetic engineering of human pluripotent cells is a prerequisite for
      exploiting their full potential. Such genetic manipulations can be achieved using
      site-specific nucleases. Here we engineered transcription activator-like effector
      nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained
      human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones
      carrying transgenic cassettes solely at the TALEN-specified location. Our data
      suggest that TALENs employing the specific architectures described here mediate
      site-specific genome modification in human pluripotent cells with similar
      efficiency and precision as do zinc-finger nucleases (ZFNs).

PMID- 21738128
TI  - Too soon to translate?

PMID- 21738129
TI  - Overwhelmed drug regulators seek cure in cooperation.

PMID- 21738130
TI  - FDA approval signals more 'homework' on the horizon in trials.

PMID- 21738131
TI  - New $10 million X Prize launched for tricorder-style medical device.

PMID- 21738132
TI  - As E. coli continues to claim lives, new approaches offer hope.

PMID- 21738133
TI  - Trial puts niacin--and cholesterol dogma--in the line of fire.

PMID- 21738134
TI  - Forty years on from Nixon's war, cancer research 'evolves'.

PMID- 21738135
TI  - Federal court raises the bar for overturning patents.

PMID- 21738136
TI  - Supreme Court decision on patent for HIV test unlikely to set major precedent.

PMID- 21738137
TI  - Companies vie for a cut of the gene-editing market.

PMID- 21738138
TI  - France adds weight to obesity research with new institute.

PMID- 21738139
TI  - After GAVI pledges surpass goals, focus shifts to keeping promises.

PMID- 21738140
TI  - Pfizer breaks from merger mentality as others chase leads.

PMID- 21738141
TI  - A shortage link?

PMID- 21738143
TI  - Straight talk with...Valery Danilenko. Interviewed by Gary Peach.
AB  - Russian medicine is-at long last-undergoing a renaissance. The country's rocky
      economic ride following the collapse of the Soviet Union disrupted its research
      rubric and impoverished its healthcare system. Now, however, the nation's
      leadership is spearheading various initiatives to reverse the situation. One of
      them, the US-Russian Scientific Forum, established two years ago by a bilateral
      presidential commission, hopes to bring improvements by facilitating public
      private research in biomedicine and innovative drugs. The Forum, which on the
      Russian side is represented by the country's Ministry of Health and Social
      Development and the Russian Academy of Sciences, among others, held its inaugural
      planning meeting in late April in Moscow. Valery Danilenko, who is helping to
      spearhead the effort and also leads the biotechnology division at the Vavilov
      Institute of General Genetics in Moscow, told Nature Medicine about the meeting
      and Russia's hopes for the Forum. The interview was conducted in Russian and
      translated by the interviewer, Gary Peach.

PMID- 21738144
TI  - The vagina catalogues.

PMID- 21738145
TI  - Good vibrations.

PMID- 21738147
TI  - Antibiotic bill doesn't GAIN enough ground.
AB  - With an eye to tackling the growing problem of antimicrobial drug resistance, uS
      lawmakers last month proposed new incentives to jump-start the ailing antibiotic
      industry. but the legislation as written is not likely to have the intended
      consequences, as it fails to adequately shield companies from competition with
      generic drugs. To truly entice investment and research from the drug industry,
      the bill needs to simplify the path to regulatory approval, provide greater
      protection from generic competition and aid drug companies with intellectual
      property extensions, tax relief and guaranteed market commitments.

PMID- 21738149
TI  - Effect of bitter tastants on human bronchi.

PMID- 21738150
TI  - Bronchodilator activity of bitter tastants in human tissue.

PMID- 21738151
TI  - Bronchodilator activity of bitter tastants in human tissue.

PMID- 21738152
TI  - Downregulating DR6 to drive remyelination.

PMID- 21738153
TI  - A downside to apoptosis in cancer therapy?

PMID- 21738154
TI  - The brain splits obesity and hypertension.

PMID- 21738155
TI  - A viral strategy to ambush tumors.

PMID- 21738156
TI  - A Nod toward understanding Crohn's pathology.

PMID- 21738157
TI  - Lung stem cells: looking beyond the hype.

PMID- 21738158
TI  - Pulling down the plug on atherosclerosis: cooling down the inflammasome.

PMID- 21738159
TI  - Pulling down the plug on atherosclerosis: finding the culprit in your heart.

PMID- 21738162
TI  - Retraction: NET loss of air in cystic fibrosis.

PMID- 21738161
TI  - The immunology of stroke: from mechanisms to translation.
AB  - Immunity and inflammation are key elements of the pathobiology of stroke, a
      devastating illness second only to cardiac ischemia as a cause of death
      worldwide. The immune system participates in the brain damage produced by
      ischemia, and the damaged brain, in turn, exerts an immunosuppressive effect that
      promotes fatal infections that threaten the survival of people after stroke.
      Inflammatory signaling is involved in all stages of the ischemic cascade, from
      the early damaging events triggered by arterial occlusion to the late
      regenerative processes underlying post-ischemic tissue repair. Recent
      developments have revealed that stroke engages both innate and adaptive immunity.
      But adaptive immunity triggered by newly exposed brain antigens does not have an
      impact on the acute phase of the damage. Nevertheless, modulation of adaptive
      immunity exerts a remarkable protective effect on the ischemic brain and offers
      the prospect of new stroke therapies. As immunomodulation is not devoid of
      deleterious side effects, a better understanding of the reciprocal interaction
      between the immune system and the ischemic brain is essential to harness the full
      therapeutic potential of the immunology of stroke.

PMID- 21738163
TI  - Retraction: CXCR2 mediates NADPH oxidase-independent neutrophil extracellular
      trap formation in cystic fibrosis airway inflammation.

PMID- 21738164
TI  - Antibiotic prophylaxis in dentistry: part I. A qualitative study of
      professionals' views on the NICE guideline.
AB  - BACKGROUND: The NICE guideline for antibiotic prophylaxis before dental treatment
      has made a substantive change and fundamental departure from previous practice
      that affects long-standing beliefs and practice patterns. There is potential
      difficulty for healthcare professionals explaining the new guidance to patients
      who have long believed that they must receive antibiotics before their dental
      treatment. AIM: To explore clinicians' attitudes towards the NICE guidance on
      antibiotic prophylaxis, their use of the guideline in clinical practice, barriers
      to the implementation of the guideline, and how best to overcome any perceived
      barriers. METHODS: In-depth interviews were conducted with seven dental care
      professionals, two cardiologists and a cardiac care nurse. The data were analysed
      using the framework method to extract central themes and opinions. RESULTS:
      Clinicians generally perceived that initially patients would be reluctant to
      follow the NICE guidance. This was felt to be particularly true of the patient
      cohort that had previously been prescribed prophylactic antibiotics. They found
      it difficult to explain the new guidance to patients who have had infective
      endocarditis and have long believed that they must receive antibiotics before
      their dental treatment. Concerns were also raised about the legal position of a
      clinician who did not follow the guidance. Clinicians generally suggested that
      the provision of accurate information in the form of leaflets and valid websites
      would be the best way to advise patients about the new guidance. CONCLUSIONS:
      Clinicians anticipated difficulties in explaining to patients the change in
      clinical practice necessitated by adherence to the NICE guidance, most notably
      for patients with a history of infective endocarditis or where the patient's
      cardiologist did not agree with the NICE guidance. They placed particular
      emphasis on the provision of accurate information in order to reassure patients.

PMID- 21738165
TI  - Antibiotic prophylaxis in dentistry: part II. A qualitative study of patient
      perspectives and understanding of the NICE guideline.
AB  - BACKGROUND: The National Institute for Health and Clinical Excellence (NICE)
      recommendations in 2008 for antibiotic prophylaxis before dental treatment
      contradict previous practice. There is a potential difficulty in explaining the
      new guidance to patients who have long believed that they must receive
      antibiotics before their dental treatment. AIM: This study investigated the
      patient-related barriers and facilitating factors in implementation of the NICE
      guidance. METHODS: In-depth interviews were conducted with nine patients
      concerning their views about barriers and factors that could influence the
      implementation of the NICE guidance on antibiotic prophylaxis before dental
      treatment. Data were analysed using framework analysis. RESULTS: For patients the
      rationale for the NICE guidance was unclear. They understood that at the
      population level the risk of infective endocarditis was less than the risk of
      adverse reaction to antibiotics. However, on an individual level they felt that
      the latter risk was negligible given their previous experience of antibiotics.
      They were aware that standards of care change over time but were concerned that
      this may be an example where a mistake had been made. Patients felt that the
      characteristics of the person advising them about the new guidance were important
      in whether or not they would accept them - they wished to be advised by a
      clinician that they knew and trusted, and who was perceived as having appropriate
      expertise. CONCLUSIONS: Patients generally felt that they would be most reassured
      by information provided by a clinician who they felt they could trust and who was
      qualified to comment on the issue by respecting their autonomy. The implications
      of the findings for the development of patient information are discussed.

PMID- 21738166
TI  - Whatever you think is best, doctor.

PMID- 21738167
TI  - Difficult to accept.

PMID- 21738168
TI  - Antibacterial twig.

PMID- 21738169
TI  - Sheath compliance.

PMID- 21738170
TI  - Bus driver threat.

PMID- 21738171
TI  - Watershed case.

PMID- 21738172
TI  - Proto-medicine.

PMID- 21738173
TI  - Tooth whitening debate steps up a few shades.

PMID- 21738178
TI  - Practitioners sought for multidisciplinary commissioning.

PMID- 21738180
TI  - Quality indicators: the rationale behind their use in NHS dentistry.
AB  - This paper explores the concept of quality as applied to healthcare and its
      subsequent application to dentistry. The assessment of quality arose from the
      manufacturing industry and is viewed as a cornerstone of current Government
      thinking. The difficulties in defining and therefore in measuring are examined
      and, in particular, the tensions between quantifying quality at a population
      level and at an individual level. The findings of the application of quality
      measures to primary medical care are reviewed, especially those that are linked
      to financial reimbursement of care providers and the implications for any future
      dental agenda discussed.

PMID- 21738182
TI  - A survey of UK dental health professionals using a medicines information service:
      what questions do they ask and do they get useful answers?
AB  - Dentists prescribe a limited range of medicines but it is important that they
      consider the effects of all medicines their patients are taking when providing
      dental care. In the UK, a national medicines information (UKMi) service funded by
      the National Health Service is available to advise health professionals on
      prescribing and to support evidence-based practice. This paper presents the
      results of a survey of 151 dental health professionals who contacted the UKMi
      service for advice. Enquiries most commonly involved antibiotics (32%), but
      dental health professionals also asked for advice on legal issues relating to
      medicines (10%), and on managing patients receiving bisphosphonates (9%), local
      anaesthetics (6%) and antiplatelet drugs (5%). One hundred and forty-six (97%)
      enquirers used the advice provided: for managing current patients, planning the
      care of future patients, for continuing professional development and teaching
      others. Two thirds of enquirers used the information provided to check if current
      or proposed management was appropriate, one half to change therapy and over one
      quarter to identify, manage or avoid adverse effects or drug interactions.

PMID- 21738187
TI  - Summary of: Antibiotic prophylaxis in dentistry: part I. A qualitative study of
      professionals' views on the NICE guideline.

PMID- 21738188
TI  - Summary of: Antibiotic prophylaxis in dentistry: part II. A qualitative study of
      patient perspectives and understanding of the NICE guideline.

PMID- 21738189
TI  - Current developments in interim transport (storage) media in dentistry: an
      update.
AB  - Healing following avulsion and replantation is dependent on the extent of pulpal
      and periodontal ligament (PDL) tissue damage. Therefore, immediate replantation
      is the recommended treatment of choice for an avulsed permanent tooth. To achieve
      a more favourable prognosis following tooth replantation, use of an appropriate
      interim transport medium is usually advocated. Numerous studies have researched
      and advocated the use of media like saliva, milk, Hank's Balanced Salt Solution
      (HBSS) and ViaSpan. However, current research has indicated the use of few newer
      media as promising interim transport media for an avulsed tooth. This review
      summarises the current developments regarding the introduction of newer interim
      transport media for the treatment of avulsed teeth.

PMID- 21738206
TI  - Smile Mumias: oral health education and dental care for children in Mumias
      District, Western Kenya (formerly the Akhonya Dental Project): one year on.
AB  - This article outlines the progress made in providing oral health education and
      basic dental care to children with special needs in the Mumias District, Western
      Province, Kenya. Included is the preparation for the project, outline of
      programme of activity, findings and discussion about oral health and dental care
      in this region of Kenya. Finally we consider future plans for this project and
      oral health provision in Kenya.

PMID- 21738213
TI  - EMU/miR-125b transgenic mice develop lethal B-cell malignancies.
AB  - MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation
      t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic
      leukemia (BCP-ALL). This translocation results in overexpression of miR-125b
      controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In
      addition, we found that six out of twenty-one BCP-ALL patients without
      t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of
      nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid
      crisis that had progressed from chronic myelogenous leukemia overexpressed miR
      125b. To examine the role of the deregulated expression of miR-125b in the
      development of B-cell tumor in vivo, we generated transgenic mice mimicking the
      t(11;14)(q24;q32) (EMU/miR-125b-TG mice). EMU/miR-125b-TG mice overexpressed miR
      125b driven by IGH enhancer and promoter and developed IgM-negative or IgM
      positive lethal B-cell malignancies with clonal proliferation. B cells obtained
      from the EMU/miR-125b-TG mice were resistant to apoptosis induced by serum
      starvation. We identified Trp53inp1, a pro-apoptotic gene induced by cell stress,
      as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo.
      Our results provide direct evidence that miR-125b has important roles in the
      tumorigenesis of precursor B cells.

PMID- 21738214
TI  - BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX
      activation.
AB  - Alkylating DNA-damage agents such as N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG)
      trigger necroptosis, a newly defined form of programmed cell death (PCD) managed
      by receptor interacting protein kinases. This caspase-independent mode of cell
      death involves the sequential activation of poly(ADP-ribose) polymerase-1 (PARP
      1), calpains, BAX and AIF, which redistributes from mitochondria to the nucleus
      to promote chromatinolysis. We have previously demonstrated that the BAX-mediated
      mitochondrial release of AIF is a critical step in MNNG-mediated necroptosis.
      However, the mechanism regulating BAX activation in this PCD is poorly
      understood. Employing mouse embryonic knockout cells, we reveal that BID controls
      BAX activation in AIF-mediated necroptosis. Indeed, BID is a link between
      calpains and BAX in this mode of cell death. Therefore, even if PARP-1 and
      calpains are activated after MNNG treatment, BID genetic ablation abolishes both
      BAX activation and necroptosis. These PCD defects are reversed by reintroducing
      the BID-wt cDNA into the BID(-/-) cells. We also demonstrate that, after MNNG
      treatment, BID is directly processed into tBID by calpains. In this way, calpain
      non-cleavable BID proteins (BID-G70A or BID-Delta68-71) are unable to promote BAX
      activation and necroptosis. Once processed, tBID localizes in the mitochondria of
      MNNG-treated cells, where it can facilitate BAX activation and PCD. Altogether,
      our data reveal that, as in caspase-dependent apoptosis, BH3-only proteins are
      key regulators of caspase-independent necroptosis.

PMID- 21738215
TI  - Glycogen synthase kinase 3beta inhibitors protect hippocampal neurons from
      radiation-induced apoptosis by regulating MDM2-p53 pathway.
AB  - Exposure of the brain to ionizing radiation can cause neurocognitive
      deficiencies. The pathophysiology of these neurological changes is complex and
      includes radiation-induced apoptosis in the subgranular zone of the hippocampus.
      We have recently found that inhibition of glycogen synthase kinase 3beta (GSK
      3beta) resulted in significant protection from radiation-induced apoptosis in
      hippocampal neurons. The molecular mechanisms of this cytoprotection include
      abrogation of radiation-induced accumulation of p53. Here we show that
      pretreatment of irradiated HT-22 hippocampal-derived neurons with small molecule
      inhibitors of GSK-3beta SB216763 or SB415286, or with GSK-3beta-specific shRNA
      resulted in accumulation of the p53-specific E3 ubiquitin ligase MDM2. Knockdown
      of MDM2 using specific shRNA or chemical inhibition of MDM2-p53 interaction
      prevented the protective changes triggered by GSK-3beta inhibition in irradiated
      HT-22 neurons and restored radiation cytotoxicity. We found that this could be
      due to regulation of apoptosis by subcellular localization and interaction of GSK
      3beta, p53 and MDM2. These data suggest that the mechanisms of radioprotection by
      GSK-3beta inhibitors in hippocampal neurons involve regulation of MDM2-dependent
      p53 accumulation and interactions between GSK-3beta, MDM2 and p53.

PMID- 21738216
TI  - TNF-alpha response of vascular endothelial and vascular smooth muscle cells
      involve differential utilization of ASK1 kinase and p73.
AB  - Atherosclerosis involves a specialized inflammatory process regulated by an
      intricate network of cytokine and chemokine signaling. Atherosclerotic lesions
      lead to the release of cytokines that can have multiple affects on various
      vascular cell functions either promoting lesion expansion or alternatively retard
      progression. Tumor necrosis factor-alpha (TNF-alpha) is one such cytokine that
      can activate both cell survival and cell death mechanisms simultaneously. Here we
      show that TNF-alpha induces apoptosis in human aortic endothelial cells (HAECs),
      while it promotes the proliferation of vascular smooth muscle cells (VSMCs). Both
      events involved the activation of the Rb-E2F1 transcriptional regulatory pathway.
      Stimulation of HAECs with TNF-alpha led to an increased expression of p73 protein
      and a reduction in the levels of p53. This involved apoptosis signal-regulating
      kinase 1 (ASK1)- mediated inactivation of Rb and its dissociation from the p73
      promoter. In contrast, TNF-alpha stimulation of VSMCs enhanced the association of
      E2F1 with proliferative promoters like thymidylate synthase and cdc25A, while Rb
      was dissociated. ASK1 kinase has a critical role in the apoptotic process, as its
      depletion or dissociation from Rb reduced TNF-alpha-induced apoptosis. These
      results show that the cytokine TNF-alpha can elicit diametrically opposite
      responses in vascular endothelial cells and VSMCs, utilizing the Rb-E2F pathway.

PMID- 21738217
TI  - Immunotherapy: pieces of the IVIG anti-inflammatory response.

PMID- 21738218
TI  - Antiviral immunity: rapid response team.

PMID- 21738219
TI  - The academic birth rate. Production and reproduction of the research work force,
      and its effect on innovation and research misconduct.

PMID- 21738220
TI  - Protein kinase D: coupling extracellular stimuli to the regulation of cell
      physiology.
AB  - Protein kinase D (PKD) mediates the actions of stimuli that promote
      diacylglycerol (DAG) biogenesis. By phosphorylating effectors that regulate
      transcription, fission and polarized transport of Golgi vesicles, as well as cell
      migration and survival after oxidative stress, PKDs substantially expand the
      range of physiological processes controlled by DAG. Dysregulated PKDs have been
      linked to pathologies including heart hypertrophy and cancer invasiveness. Our
      understanding of PKD regulation by trans- and autophosphorylation, as well as the
      subcellular dynamics of PKD substrate phosphorylation, have increased markedly.
      Selective PKD inhibitors provide new, powerful tools for elucidating the
      physiological roles of PKDs and potentially treating cardiac disease and cancer.

PMID- 21738221
TI  - Multilayer checkpoints for microRNA authenticity during RISC assembly.
AB  - MicroRNAs (miRNAs) function through the RNA-induced silencing complex (RISC),
      which contains an Argonaute (Ago) protein at the core. RISC assembly follows a
      two-step pathway: miRNA/miRNA* duplex loading into Ago, and separation of the two
      strands within Ago. Here we show that the 5' phosphate of the miRNA strand is
      essential for duplex loading into Ago, whereas the preferred 5' nucleotide of the
      miRNA strand and the base-pairing status in the seed region and the middle of the
      3' region function as additive anchors to Ago. Consequently, the miRNA
      authenticity is inspected at multiple steps during RISC assembly.

PMID- 21738222
TI  - Reconstitution of the Mycobacterium tuberculosis pupylation pathway in
      Escherichia coli.
AB  - Prokaryotic ubiquitin-like protein (Pup) is a post-translational modifier that
      attaches to more than 50 proteins in Mycobacteria. Proteasome accessory factor A
      (PafA) is responsible for Pup conjugation to substrates, but the manner in which
      proteins are selected for pupylation is unknown. To address this issue, we
      reconstituted the pupylation of model Mycobacterium proteasome substrates in
      Escherichia coli, which does not encode Pup or PafA. Surprisingly, Pup and PafA
      were sufficient to pupylate at least 51 E. coli proteins in addition to the
      mycobacterial proteins. These data suggest that pupylation signals are intrinsic
      to targeted proteins and might not require Mycobacterium-specific cofactors for
      substrate recognition by PafA in vivo.

PMID- 21738223
TI  - SIRT3 deacetylase: the Jekyll and Hyde sirtuin.

PMID- 21738224
TI  - Identification of the AFD neuron as the site of action of the CREB protein in
      Caenorhabditis elegans thermotaxis.
AB  - Behaviour is a consequence of computation in neural circuits composed of massive
      synaptic connections among sensory neurons and interneurons. The cyclic AMP
      response element-binding protein (CREB) responsible for learning and memory is
      expressed in almost all neurons. Nevertheless, we find that the Caenorhabditis
      elegans CREB orthologue, CRH-1, is only required in the single bilateral
      thermosensory neuron AFD, for a memory-related behaviour. Restoration of CRH-1 in
      AFD of CREB-depleted crh-1 mutants rescues its thermotactic defect, whereas
      restorations in other neurons do not. In calcium-imaging analyses, the AFD
      neurons of CREB-depleted crh-1 mutants exhibit an abnormal response to
      temperature increase. We present a new platform for analysing the mechanism of
      behavioural memory at single-cellular resolution within the neural circuit.

PMID- 21738225
TI  - GTP binding to the ROC domain of DAP-kinase regulates its function through
      intramolecular signalling.
AB  - Death-associated protein kinase (DAPk) was recently suggested by sequence
      homology to be a member of the ROCO family of proteins. Here, we show that DAPk
      has a functional ROC (Ras of complex proteins) domain that mediates homo
      oligomerization and GTP binding through a defined P-loop motif. Upon binding to
      GTP, the ROC domain negatively regulates the catalytic activity of DAPk and its
      cellular effects. Mechanistically, GTP binding enhances an inhibitory
      autophosphorylation at a distal site that suppresses kinase activity. This study
      presents a new mechanism of intramolecular signal transduction, by which GTP
      binding operates in cis to affect the catalytic activity of a distal domain in
      the protein.

PMID- 21738226
TI  - Regulation of Rad51 function by phosphorylation.
AB  - Rad51 is a key enzyme involved in DNA double-strand break repair by homologous
      recombination. Here, we show that in response to DNA damage, budding yeast Rad51
      is phosphorylated on Ser 192 in a manner that is primarily mediated by the DNA
      damage-responsive protein kinase Mec1. We show that mutating Rad51 Ser 192 to Ala
      or Glu confers hypersensitivity to DNA damage and homologous-recombination
      defects. Furthermore, biochemical analyses indicate that Ser 192 is required for
      Rad51 adenosine triphosphate hydrolysis and DNA-binding activity in vitro,
      whereas mutation of Ser 192 does not interfere with Rad51 multimer formation.
      These data suggest a model in which Mec1-mediated phosphorylation of Rad51 Ser
      192 in response to DNA damage controls Rad51 activity and DNA repair by
      homologous recombination.

PMID- 21738227
TI  - Primary signet ring cell carcinoma of the eyelid in a young woman.

PMID- 21738228
TI  - Long-term presence of metallic particles in the DSAEK interface.

PMID- 21738229
TI  - Serum C-reactive protein levels in exfoliation syndrome and exfoliative glaucoma.

PMID- 21738230
TI  - Bevacizumab prior to vitrectomy for diabetic traction retinal detachment.
AB  - PURPOSE: To assess the efficacy and safety of preoperative intravitreal
      bevacizumab (IVB) before vitrectomy for diabetic tractional retinal detachment
      (TRD). METHODS: Using ICD-9 codes, we located all patients with diabetic TRD who
      underwent 3-port 20-gauge vitrectomy primarily performed by one surgeon between
      January 2004 and January 2009. Eyes receiving IVB were compared with those not.
      The following outcomes were compared: visual acuity (VA), duration of surgery,
      and complication rates. RESULTS: A total of 99 eyes of 90 patients were included
      in the analysis. In all, 34 patients received IVB on an average of 11.5 (range, 3
      30) days previtrectomy. Age was 46.5 and 51.6 in the IVB and non-IVB groups,
      respectively. VA was improved significantly in both groups: from 20/617 to 20/62
      in the IVB group, and from 20/443 to 20/86 in the non-IVB group (P=0.11 between
      groups). Operating time and postoperative complications (glaucoma, RD, and
      revitrectomy rate) were similar in both groups. On comparing IVB and non-IVB eyes
      in younger patients (<= 40), operating time was shorter (P=0.02) and a trend to
      better VA in the IVB group was seen. CONCLUSIONS: Preoperative IVB may be a
      useful adjunct to vitrectomy for severe PDR complicated by TRD, particularly in
      younger diabetics.

PMID- 21738231
TI  - The influence of cortical, nuclear, subcortical posterior, and mixed cataract on
      the results of microperimetry.
AB  - PURPOSE: Microperimetry is a useful instrument for evaluating sensitivity
      threshold due to retinal pathologies. The aim of the study is to assess the
      impact of different forms of cataract on microperimetry results. METHODS: In a
      prospective design, patients were recruited for cataract surgery at the
      Department of Ophthalmology, Medical University of Vienna. Exclusion criteria
      were any other ophthalmic disease except cataract, that is, macular pathology.
      Using the Lens Opacities Classification System III classification, patients were
      classified into four groups: nuclear, cortical, subcapsular posterior, and mixed
      cataract. Then patients underwent microperimetry: results were analyzed for
      magnitude of retinal sensitivity loss and correlated to the forms and density of
      the cataract. RESULTS: Mean density of cataract was LOCS 3.2-3.5 in the four
      groups. Differences were not statistically significant. The best-corrected visual
      acuity (BCVA) was LogMAR 0.5 +/- 0.13 in nuclear, LogMAR 0.49 +/- 0.21 in
      cortical, and LogMAR 0.58 +/- 0.12 in mixed cataract patients, and significantly
      worse in patients with subcapsular posterior cataract (LogMAR 0.64 +/- 0.12).
      Microperimetry shows a mean sensitivity of 11.4-12.6 dB without significant group
      differences. The BCVA is correlated with microperimetry in patients with nuclear
      and cortical cataract. Density of cataract is highly correlated with
      microperimetry results in all groups. CONCLUSION: The present study shows a good
      correlation of microperimetry results with the BCVA of patients with nuclear and
      cortical cataract. In patients with subcapsular posterior cataract,
      microperimetry results were better than estimated by BCVA. Density of cataract is
      highly correlated with macular sensitivity. A reduction of 1 dB in microperimetry
      per 1 posterior capsule opacification score increase can be estimated for these
      patients.

PMID- 21738232
TI  - Spectral domain optical coherence tomography macular cube scans and retinal
      pigment epithelium/drusen maps may fail to display subretinal drusenoid deposits
      (reticular pseudodrusen) in eyes with non-neovascular age-related macular
      degeneration.

PMID- 21738233
TI  - The use of propranolol in the management of periocular capillary haemangioma--a
      systematic review.
AB  - Capillary haemangioma or infantile haemangioma (IH) is the most common congenital
      vascular tumour in the periocular region. Several treatment modalities have been
      documented, with variable degree of success. Propranolol has recently been
      reported to be an effective and safe alternative. The aim of this systematic
      review is to examine the evidence base for the use of propranolol administered
      orally in the management of periocular capillary haemangioma, and use this
      information to guide future research. A systematic review of literature was
      carried out by two independent reviewers using the search strategies highlighted
      below. A total of 100 cases of oral propranolol use in periorbital or orbital
      capillary haemangiomas have been documented in the literature. Of the 85 cases
      that had details of previous treatment, it was used as first-line treatment in 50
      (58.8%). The commonest dose used was 2 mg/kg/day. Adverse events were documented
      in one-third of cases; in most cases these were minor. Improvement or complete
      resolution of the lesions occurred in 96% of cases. Recurrence was noted in one
      fifth of cases. Propranolol has shown a lot of promise in the therapy of IH and
      further research in the form of properly designed randomized trials is certainly
      warranted. Treatment guidelines based on literature available to date is included
      in this review.

PMID- 21738234
TI  - Relative hypoadiponectinemia, insulin resistance, and increased visceral fat in
      euthyroid prepubertal girls with low-normal serum free thyroxine.
AB  - A lower activity of the thyroid axis within the clinical reference range is
      related to a dysmetabolic phenotype in adult populations. We posited that such an
      association is already present as early as in prepubertal childhood. Serum
      thyroid stimulating hormone (TSH) and free T4, body fat (bioelectric impedance),
      insulin resistance (homeostasis model assessment of insulin resistance
      (HOMA(IR))), total and high molecular weight (HMW)-adiponectin and serum lipids
      were assessed in 234 euthyroid prepubertal children (113 boys and 121 girls)
      attending primary care clinics. Visceral fat (abdominal ultrasound) was measured
      in a subset of these subjects (n = 147; 74 boys and 73 girls). Explants of
      visceral adipose tissue from an additional six prepubertal children (three boys
      and three girls) were used to study the regulation of total and HMW-adiponectin
      by thyroid hormone. Serum free T4 was in girls independently associated with HMW
      adiponectin, HOMA(IR) and visceral fat, so that circulating HMW-adiponectin
      decreased by 30% (beta = 0.305 P < 0.005, R(2) = 0.13) and HOMA(IR) and visceral
      fat increased, respectively, by 90% (beta = -0.255 P < 0.01, R(2) = 0.05) and 30%
      (beta = -0.369, P < 0.005, R(2) = 0.12) from the highest to the lowest tertile of
      serum free T4. Nonsignificant differences in these parameters were found in boys.
      Treatment of visceral fat explants with thyroid hormone increased total and HMW
      adiponectin by 70% and 53%, respectively, above control values (P < 0.01). In
      conclusion, a dysmetabolic phenotype, consisting of relative hypoadiponectinemia,
      insulin resistance and increased visceral fat, is associated with low-normal
      serum free thyroxine in euthyroid prepubertal girls. These associations may be
      partly explained by a positive regulation of HMW-adiponectin secretion by thyroid
      hormone.

PMID- 21738235
TI  - Visceral obesity is a negative predictor of remission of diabetes 1 year after
      bariatric surgery.
AB  - Our aim was to identify preoperative anthropometric and clinical parameters that
      predict the remission of diabetes after Roux-en-Y gastric bypass (RYGB). Fifty
      severely obese Korean patients with type 2 diabetes underwent RYGB. Visceral and
      abdominal subcutaneous fat area (SFA) was assessed using computed tomography
      before and 6 and 12 months after RYGB. Remission was defined as a glycated
      hemoglobin (A(1C)) level <6.5% and a fasting glucose concentration <126 mg/dl for
      1 year or more without the use of medication. The visceral-to-SFA ratio decreased
      from 0.60 +/- 0.30 to 0.53 +/- 0.29 (P = 0.001) after 6 months and decreased
      further to 0.42 +/- 0.24 (P < 0.001) after 12 months. Thirty-four of the 50
      patients (68%) had remission of diabetes (remission group). Compared with
      patients in the nonremission group, patients in the remission group had a shorter
      duration of diabetes and lower preoperative A(1C) level, and were less likely to
      use insulin preoperatively. Preoperative BMI did not differ in two groups.
      However, the preoperative visceral-to-SFA ratio was greater in the nonremission
      group compared with the remission group (0.79 +/- 0.29 vs. 0.53 +/- 0.26, P =
      0.003). Finally, the preoperative visceral-to-SFA ratio was an independent
      predictor of the remission of diabetes after RYGB in multiple stepwise logistic
      regression analysis. In conclusion, our data suggest that visceral adiposity
      negatively influence the likelihood of the patient experiencing the remission of
      diabetes after RYGB.

PMID- 21738236
TI  - Influence of abdominal obesity on vascular endothelial function in
      overweight/obese adult men.
AB  - It has been suggested that body fat distribution may be an important determinant
      of the impact of adiposity on endothelial function. We tested the hypothesis that
      overweight/obese adults with abdominal adiposity exhibit worse endothelial
      vasodilator and fibrinolytic function than overweight/obese adults without
      abdominal adiposity. Sixty adult men were studied: 20 normal weight (BMI: 22.3 +/
      0.7 kg/m2; waist circumference (WC): 84.9 +/- 2.0 cm); 20 overweight/obese with
      WC <102 cm (29.2 +/- 0.3 kg/m2; 98.1 +/- 0.7 cm); and 20 overweight/obese with WC
      >=102 cm (30.0 +/- 0.4 kg/m2; 106.7 +/- 1.0 cm). Forearm blood flow (FBF)
      responses to intra-arterial acetylcholine and sodium nitroprusside (SNP) were
      measured. Additionally, net endothelial release of tissue-type plasminogen
      activator (t-PA) was determined in response to bradykinin (BK) and SNP.
      Overweight/obese men demonstrated lower (~30%; P < 0.01) FBF responses to
      acetylcholine compared with normal weight controls. However, there were no
      differences in FBF responses to acetylcholine between overweight/obese men with
      (4.1 +/- 0.3-10.8 +/- 1.3 ml/100 ml tissue/min) and without (4.5 +/- 0.3-11.6 +/-
      0.8 ml/100 ml tissue/min) abdominal adiposity. Similarly, endothelial t-PA
      release to BK was lower (~40%; P < 0.05) in the overweight/obese men compared
      with normal weight controls; however, t-PA release was not different between the
      overweight/obese men with (-0.7 +/- 0.4-40.4 +/- 6.2 ng/100 ml tissue/min) and
      without (-0.3 +/- 0.6-48 +/- 7.5 ng/100 ml tissue/min) abdominal adiposity. These
      results indicate that abdominal obesity is not associated with greater impairment
      in endothelial vasodilation and fibrinolytic capacity in overweight/obese men.
      Excess adiposity, regardless of anatomical distribution pattern, is associated
      with impaired endothelial function.

PMID- 21738237
TI  - C-reactive protein modifies the association of plasma leptin with coronary
      calcium in asymptomatic overweight individuals.
AB  - Evidence suggests putative interactions of leptin and C-reactive protein (CRP) in
      the pathogenesis of adiposity-related atherosclerotic cardiovascular disease
      (CVD). Therefore, we investigated whether CRP levels modify the relationship of
      leptin levels with coronary artery calcium (CAC). We examined 1,460 asymptomatic
      individuals from two community-based cross-sectional studies coordinated at a
      single, university-based research center. We focused on subjects who were
      overweight or obese (BMI >=25) given greater biologic plausibility in this
      setting. In multivariable CAC models, we analyzed the interaction of log
      transformed plasma leptin levels with higher CRP levels as defined by three cut
      points: two clinically based (2 mg/l, 3 mg/l) and one dataset specific (sex
      specific upper quartile). The association of plasma leptin with CAC was modified
      by higher CRP regardless of cut-point (interaction term P values all <0.01 in
      fully adjusted models). Leptin levels were associated with CAC in those with
      high, but not low CRP levels (e.g., tobit ratio for a 1 unit increase in
      ln(leptin) (95% CI): 2.18 (1.29-3.66) if CRP level >=3 mg/l; N = 461 vs. 0.94
      (0.67-1.31) if CRP levels <3 mg/l; N = 999) in fully adjusted models. No
      interaction with CRP was present in control analyses with adiponectin, BMI and
      waist circumference. In conclusion, in asymptomatic overweight and obese adults,
      increased leptin levels were independently associated with increased CAC in the
      presence of high, but not low CRP levels, supporting a leptin-CRP interface in
      atherosclerosis risk.

PMID- 21738238
TI  - Rescue of melanocortin 4 receptor (MC4R) nonsense mutations by aminoglycoside
      mediated read-through.
AB  - Aminoglycoside-mediated read-through of stop codons was recently demonstrated for
      a variety of diseases in vitro and in vivo. About 30 percent of human genetic
      diseases are the consequence of nonsense mutations. Nonsense mutations in obesity
      associated genes like the melanocortin 4 receptor (MC4R), expressed in the
      hypothalamus, show the impact of premature stop codons on energy homeostasis.
      Therefore, the MC4R could be a potential pharmaceutical target for obesity
      treatment and targeting MC4R stop mutations could serve as proof of principle for
      nonsense mutations in genes expressed in the brain. We investigated four
      naturally occurring nonsense mutations in the MC4R (W16X, Y35X, E61X, Q307X)
      located at different positions in the receptor for aminoglycoside-mediated
      functional rescue in vitro. We determined localization and amount of full-length
      protein before and after aminoglycoside treatment by fluorescence microscopy,
      cell surface and total enzyme linked immunosorbent assay (ELISA). Signal
      transduction properties were analyzed by cyclic adenosine monophosphate (cAMP)
      assays after transient transfection of MC4R wild type and mutant receptors into
      COS-7 cells. Functional rescue of stop mutations in the MC4R is dependent on: (i)
      triplet sequence of the stop codon, (ii) surrounding sequence, (iii) location
      within the receptor, (iv) applied aminoglycoside and ligand. Functional rescue
      was possible for W16X, Y35X (N-terminus), less successful for Q307X (C-terminus)
      and barely feasible for E61X (first transmembrane domain). Restoration of full
      length proteins by PTC124 could not be confirmed. Future pharmaceutical
      applications must consider the potency of aminoglycosides to restore receptor
      function as well as the ability to pass the blood-brain barrier.

PMID- 21738239
TI  - Beliefs about weight gain among young adults: potential challenges to prevention.
AB  - This study assessed young adults' beliefs about weight gain with the goal of
      improving intervention efforts with this high-risk group. A total of 1,347
      incoming freshman (45% male; 81% non-Hispanic white; 18.6 +/- 1.7 years; BMI =
      23.3 +/- 2.3 kg/m2) at a large state university in the Northeast completed a
      survey designed to assess: (i) degree of concern about weight gain, (ii) level of
      interest in weight control programs, and (iii) the most acceptable setting for an
      intervention. Perceptions about freshman weight gain were consistent across
      gender, with men and women reporting that the average student gains 5.4 +/- 1.9
      kg and 5.6 +/- 1.9 kg respectively. Men in general were less concerned about
      weight gain (P < 0.001) and reported they would have to gain 6.2 +/- 4.2 kg
      before becoming concerned compared to 3.1 +/- 1.7 kg among women (P < 0.001).
      Overweight (OW) men were more concerned about gaining weight than normal weight
      (NW) men (P < 0.001) and indicated they would have to gain less weight before
      becoming concerned (5.0 +/- 3.0 kg vs. 6.7 +/- 4.5 kg, P < 0.001). Fewer men
      reported they would join a program to prevent weight gain (17% men vs. 40% women,
      P < 0.001); the percentage of men willing to join a prevention program did not
      vary by weight status (P = 0.59). Both men and women were most likely to report a
      willingness to attend classes on a local college campus compared to other
      settings. Findings highlight the challenges of engaging young adults in weight
      gain prevention programs, particularly young men, and are discussed in terms of
      implications for improving recruitment efforts and intervention development with
      this population.

PMID- 21738240
TI  - Validation of ultrasound estimates of visceral fat in black South African
      adolescents.
AB  - Accurate quantification of visceral adipose tissue (VAT) is needed to understand
      ethnic variations and their implications for metabolic disease risk. The use of
      reference methods such as computed tomography (CT) and magnetic resonance imaging
      (MRI) is limited in large epidemiological studies. Surrogate measures such as
      anthropometry and dual-energy X-ray absorptiometry (DXA) do not differentiate
      between VAT and subcutaneous abdominal adipose tissue (SCAT). Ultrasound provides
      a validated estimate of VAT and SCAT in white populations. This study aimed to
      validate the use of ultrasound-based assessment of VAT in black South African
      adolescents. One hundred healthy adolescents (boys = 48, girls = 52) aged 18-19
      years participating in the birth to twenty cohort study had VAT and SCAT measured
      by single slice MRI at L4. These MRI "criterion measures" were related to
      ultrasound VAT and SCAT thickness, anthropometry (BMI, waist and hip
      circumferences), and DXA android region fat. Ultrasound VAT thickness showed the
      strongest correlations with MRI VAT (Spearman's correlation coefficients: r =
      0.72 and r = 0.64; in boys and girls, respectively), and substantially improved
      the estimation of MRI VAT compared to anthropometry and DXA alone; in regression
      models the addition of ultrasound VAT thickness to models containing BMI, waist,
      and DXA android fat improved the explained variance in VAT from 39% to 60% in
      boys, and from 31% to 52% in girls. In conclusion, ultrasound substantially
      increased the precision of estimating VAT beyond anthropometry and DXA alone.
      Black South African adolescents have relatively little VAT compared to elderly
      whites, and we therefore provide new ultrasound-based prediction equations for
      VAT specific to this group.

PMID- 21738241
TI  - Myocardial oxygen consumption change predicts left ventricular relaxation
      improvement in obese humans after weight loss.
AB  - Obesity adversely affects myocardial metabolism, efficiency, and diastolic
      function. Our objective was to determine whether weight loss can ameliorate
      obesity-related myocardial metabolism and efficiency derangements and that these
      improvements directly relate to improved diastolic function in humans. We studied
      30 obese (BMI >30 kg/m2) subjects with positron emission tomography (PET)
      (myocardial metabolism, blood flow) and echocardiography (structure, function)
      before and after marked weight loss from gastric bypass surgery (N = 10) or
      moderate weight loss from diet (N = 20). Baseline BMI, insulin resistance,
      hemodynamics, left ventricular (LV) mass, systolic function, myocardial oxygen
      consumption (MVO2), and fatty acid (FA) metabolism were similar between the
      groups. MVO2/g decreased after diet-induced weight loss (P = 0.009). Total MVO2
      decreased after dietary (P = 0.02) and surgical weight loss (P = 0.0006) and was
      related to decreased BMI (P = 0.006). Total myocardial FA utilization decreased
      (P = 0.03), and FA oxidation trended lower (P = 0.06) only after surgery. FA
      esterification and LV efficiency were unchanged. After surgical weight loss, LV
      mass decreased by 23% (Doppler-derived) E/E' by 33%, and relaxation increased
      (improved) by 28%. Improved LV relaxation related significantly to decreased BMI,
      insulin resistance, total MVO2, and LV mass but not FA utilization. Decreased
      total MVO(2) predicted LV relaxation improvement independent of BMI change (P =
      0.02). Weight loss can ameliorate the obesity-related derangements in myocardial
      metabolism and LV structure and diastolic function. Decreased total MVO2
      independently predicted improved LV relaxation, suggesting that myocardial oxygen
      metabolism may be mechanistically important in determining cardiac relaxation.

PMID- 21738242
TI  - Diagnostic criteria of antibody-mediated rejection in kidney transplants.
AB  - The diagnosis and treatment of anti-donor antibody-mediated rejection or humoral
      rejection (ABMR) is one of the main discussions at the moment in kidney
      transplantation. The search for histopathological markers that help us to
      diagnose ABMR has been more problematic, in contrast to the histological
      expression of cellular or tubulointerstitial rejection. Although the relationship
      between post-transplant anti-donor antibodies and the allograft's prognosis has
      been a topic of discussion for a long time, led in the main by P.Terasaki, it was
      not until the beginning of 1990s when P. Halloran studied the humoral mechanisms
      of rejection in greater depth. Feutch described the importance of C4d deposits as
      a marker that shows a humoral mechanism of allograft rejection in 1993. As a
      result of many studies carried out, the Banff consensus group established some
      diagnostic histopathological criteria of acute (ABMR) in 2003. These have been
      modified slightly in later meetings of the group. Furthermore, in 2005 this same
      working group looked at the physiopathological mechanisms causing chronic
      allograft failure in more detail and established the criteria defining chronic
      humoral rejection. In this review, we are trying to update any useful
      histopathological criteria for diagnosing acute and chronic ABMR.

PMID- 21738243
TI  - Reasons why therapeutic apheresis should belong to nephrology.

PMID- 21738244
TI  - Causes and consequences of proteinuria following kidney transplantation.
AB  - Proteinuria is common following kidney transplantation and affects more than 40%
      of kidney transplant patients per year. In general, the level of proteinuria is
      low (<500 mg/day) but even those levels significantly reduce graft and patient
      survival. This is why it is of vital importance to detect proteinuria quickly
      following transplantation and to investigate its cause. During the same year of
      the transplant, proteinuria may be caused by multiple factors, including
      glomerular disease, effects of anti-HLA class II antibodies and drugs such as
      mTOR inhibitors, tubulointerstitial disease of the graft, and significant
      functional discrepancy between the graft and the recipient. The relationship
      between proteinuria and graft survival is likely to be due to the factors that
      cause proteinuria. It is unknown why proteinuria and patient survival are
      related, but it could be due to a relationship between proteinuria and
      traditional cardiovascular risk factors or a relationship between proteinuria,
      endothelial function and inflammation. To treat proteinuria, three aspects should
      be considered: the cause of proteinuria, the non-specific reduction of
      proteinuria, and the reduction of the cardiovascular risk.

PMID- 21738245
TI  - Patients treated with plasmapheresis: a case review from University Hospital of
      the Canary Islands.
AB  - INTRODUCTION: Plasmapheresis (PP) is a therapeutic apheresis technique used in
      the treatment of various renal and systemic diseases with varying degrees of
      proven clinical efficacy. OBJECTIVE: To review our experience with PP at the
      Hospital Universitario de Canarias, focused on effectiveness and safety results
      in different disease groups. MATERIAL AND METHODS: A retrospective-descriptive
      study of patients treated with PP from 01/01/2006 to 31/12/2009 at the hospital.
      We analysed medical histories and demographic data (sex, age), biochemical
      parameters, underlying disease, volume and type of replacement used in the PP
      sessions (5% human albumin and/or fresh frozen plasma), complications with the
      technique, delay in starting PP treatment after suspected clinical diagnosis,
      number of PP sessions received, patient mortality, degree of renal impairment and
      evolution of renal function. RESULTS: There were 51 patients studied, aged 50+/
      18 years, of whom 60% were male; 331 PP sessions were performed. The diseases
      treated were grouped as: 11 vasculitis, 15 transplant immune activation, 5
      haemolytic-uraemic syndrome (HUS), 7 idiopathic or thrombotic thrombocytopaenic
      purpura, 2 foetal Rh immunisations, 2 haematological diseases, 4 neurological
      diseases, among others. Overall mortality was 19.6% (n=10): 6 cases secondary to
      septic shock and the rest as a result of the evolution of the underlying disease,
      with 1 due to haemorrhagic shock in the renal biopsy area. There were no deaths
      in the transplant immune activation group. In the vasculitis group, there were 3
      deaths (2 secondary to septic shock). Of the 10 patients who died, 9 did so
      within the first three months after diagnosis. Of the 26 renal biopsies
      performed, the most frequent indications were: vasculitis (23%), humoral
      rejection (42%), humoral rejection with calcineurin-inhibitor toxicity (12%) and
      HUS (8%), among others. Haemodialysis (HD) was required by 24 patients at the
      start of clinical symptoms: 9 of the 11 patients with vasculitis, 4 of the 5
      patients with HUS and 5 of the 15 patients with transplant immune activation. At
      the end of evolution, 14 of them remained on the HD programme: 5 of the 11
      patients with vasculitis, 2 of the 15 transplant patients and 3 of the 5 HUS
      patients. Significantly, patients who developed end kiney disease (EKD) in the
      vasculitis group were older and had higher creatinine at the onset of the
      disease. The transplant patients were monitored for anti-HLA class I or II before
      and after PP; there was a mean decrease of antibody titres in all but one
      patient; with an average decrease of 51% to 31%. In general, the PP technique was
      virtually free of complications. There were only 5 (3%) mild-moderate reactions
      to fresh plasma (perioral tingling and urticarial reactions) requiring pre
      medication with steroids, but which did not lead to discontinuation of the
      treatment. CONCLUSION: Taking into account the wide variety of diseases that can
      benefit from PP and the nature of some of them, publishing our experience with
      this therapeutic method is of great importance. By increasing the description of
      case series by centre, we can add survival and renal function evidence in many
      uncommon diseases. Our study provides useful information for clinical practice
      and has also led us to reflect on future strategies to optimise outcomes in our
      patients.

PMID- 21738246
TI  - Obligatory referral among other factors associated with peritonitis in peritoneal
      dialysis patients.
AB  - AIM: Peritonitis is one of the major comorbidities of peritoneal dialysis (PD)
      patients. The aim of this study was to concentrate on potential risk factors,
      including more recently studied ones among the classical ones for peritonitis, in
      PD patients. MATERIALS AND METHODS: We analysed 109 patients (F/M = 42/67)
      followed up at least for 3 months in a single centre, a tertiary referral
      hospital for 360.1 patient years. In the study which is designed as a
      retrospective cohort study, demographic characteristics, conditions for choosing
      PD, type of PD treatment, some chemical tests and peritonitis episodes were
      recorded from the files of the patients. RESULTS: The rate of peritonitis was
      found to be 0.22 episode/patient year and 22 (20.18%) of the patients had more
      than one episode. Twenty seven (24.8%) of the patients were allocated to PD due
      to obligatory reasons. According to multiple regression analysis, the associated
      factors were found to be PD allocation type (obligatory versus voluntary) (p =
      0.04; RR = 2.6), serum albumin level (p = 0.05; RR = 1.2), and anti-hepatitis C
      Virus Antibody positivity (p = 0.03; RR = 1.6). Frequency of female patients were
      significantly higher in the group who had multiple episodes (p = 0.01).
      CONCLUSION: Obligatory referral which can be an indication of loss of motivation
      for peritoneal dialysis procedures, is thought to be a strong risk factor for
      peritonitis in PD patients and should be further studied. Patients with multiple
      episodes had a higher frequency of obligatory referral as expected and
      additionally, they were higher in number of females when compared to the ones
      with single episode.

PMID- 21738248
TI  - Exploring the opinion of CKD patients on dialysis regarding end-of-life and
      Advance Care Planning.
AB  - Advance care planning (ACP) and the subsequent advance directive document (ADD),
      previously known as "living wills", have not been widely used in Spain. The
      Ethics Group from the Spanish Society of Nephrology has developed a survey in
      order to investigate the opinion of dialysis patients regarding the ADD and end
      of-life care. Patients received documentation explaining ACP and filled out a
      survey about their familiarity with and approval of the ADD. Seven hospital
      dialysis centres participated in the study for a total of 416 active dialysis
      patients. Questionnaires were distributed to 263 patients, 154 of which answered
      (69.2% completed them without assistance). The rates for ADD implementation
      (7.9%) and designation of a representative person (6.6%) were very low. Most of
      the patients clearly expressed their wishes about irreversible coma, vegetative
      state, dementia and untreatable disease. More than 65% did not want mechanical
      ventilation, chronic dialysis, tube feeding or resuscitation if cardiorespiratory
      arrest occurred. They reported that an ADD could be done before starting dialysis
      but most thought that it should be offered only to those who requested it (65% vs
      34%). In conclusion, patients have clear wishes about end-of-life care, although
      these desires had not been documented due to the very low implementation of the
      ADD.

PMID- 21738247
TI  - Peritoneal dialysis and kidney transplant. A two-way ticket in an integrated
      renal replacement therapy model.
AB  - BACKGROUND: Peritoneal dialysis (PD) seems to be a good option to initiate renal
      replacement therapy (RRT), but patients with graft failure choose PD less
      frequently than incident patients (de novo). OBJECTIVE: To describe patient
      movements between PD and kidney transplantation (TX) and risk factors for failure
      of the PD technique. METHOD: Multicentre observational study of patients starting
      PD between 2003 and 2009 with follow-up up until January 2010. Survival analysis
      based on switching from PD to HD as an event using Kaplan-Meier (KM) and forward,
      stepwise Cox proportional hazards models. Hazard ratio and 95% confidence
      intervals (HR [CI]) are shown. MAIN VARIABLE: Switch from PD to HD. Two-group
      comparison: PD post transplant (post-TX) patients (76) compared to pure incident
      PD (de novo-PD) patients (830). PATIENTS: 906 PD patients from 19 public
      hospitals with a mean age of 54.8 years (64.9% male); main ESRD aetiology:
      glomerulonephritis (25.4%), diabetes (16.7%), vascular-ischaemic (10.7%),
      interstitial (13.6%) and polycystic (11.2%). Comorbidity conditions: Charlson
      Index 5.1 (SD 2.4); 21.6% diabetes mellitus (DM), 24.0% cardiovascular (CV)
      events. RESULTS: Mean follow-up period on PD: 1.85 years (95% CI [1.68-2.02
      years]). KM estimation for switching to HD due to PD failure was 5.46 years [4.42
      6.50 years]. At the end of follow-up, 88 patients had died, 154 had been
      transferred to HD and 306 had received a graft (annual rate for patients on
      waiting list: 0.49 TX per year on PD). The best Cox multivariate model for
      switching from PD to HD includes: post-TX (HR: 1.63 [1.01-2.63]), DM (HR: 1.69
      [1.19-2.40]) and age (1.01 [1.00-1.02]) per year. Post-TX patients were younger
      (43.8 years vs 55.3 years) and with less comorbidity conditions than de novo-PD
      patients (DM 18.4% vs 21.9%; CV 15.8% vs 24.7%). However post-TX patients had
      worse clinical evolution with a rapid decline of renal function (?-3.88 vs -1.8
      ml/min per year); a higher admission rate (0.9 vs 0.62 per year) but similar
      peritonitis rate (0.45 vs 0.53 episodes per year). They also needed to be
      transferred to HD more frequently (28.9% vs 15.8%; P<.006) and needed more time
      to TX (4.8 years vs 1.7 years, Kaplan-Meier). Consequently, time spent on PD was
      higher in the post-TX group (2.8 vs 1.8 year). LIMITATIONS: Observational study
      with absence of a standard protocol to switch PD-HD. CONCLUSION: PD seems to be a
      good first choice technique due to low mortality and high TX ratio in our area. A
      previous graft failure is associated with a higher rate of PD-failure but time
      spent on PD is enough to consider this technique as a good option.

PMID- 21738249
TI  - Ozone postconditioning in renal ischaemia-reperfusion model. Functional and
      morphological evidences.
AB  - BACKGROUND: Ischaemia-reperfusion is one of the main causes of kidney
      complications. The most frequent lesion is acute tubular necrosis. Ozone
      oxidative preconditioning exerts a modulatory effect of redox state of renal
      cells in models of ischaemia-reperfusion, by stimulating endogenous antioxidant
      mechanisms. Similar results have been obtained in more recent studies using
      ischaemic postconditioning. OBJECTIVES: To evaluate the effect of ozone oxidative
      postconditioning on renal function and morphology in an ischaemia-reperfusion rat
      model. METHODS: We used forty female Wistar rats weighing between 150g-200g
      randomly divided into 4 groups (negative control, positive control, oxygen and
      ozone). The groups: positive control, oxygen and ozone were subjected to 60
      minutes of ischaemia and 10 days of reperfusion. During reperfusion, the oxygen
      group was given 26mg/kg body weight of oxygen, and the ozone group 0.5mg/kg body
      weight of ozone, rectally. At the end of the experiment urine and blood samples
      were taken for renal function tests and kidneys were removed for histological
      study. RESULTS: The ozone group showed no significant differences for filtration
      fraction and proteinuria compared to the negative control group. The glomerular
      filtrate rate, renal plasma flow and creatinine showed a slight improvement in
      comparison with oxygen and positive control groups. The ozone group showed
      significantly less overall histological damage than the positive control and
      oxygen groups. CONCLUSIONS: Ozone postconditioning showed to have a protective
      effect in preserving renal function and morphology.

PMID- 21738250
TI  - How do disorders related to hospitalisation influence haemodialysis patients'
      nutrition?
AB  - INTRODUCTION: Hospitalizations are frequent in hemodialysis patients and is often
      accompanied by nutritional deterioration showed by a loss of weight and a
      reduction of albumin serum levels. This phenomenon is related with length of stay
      having its origin in a complex interplay of factors. Our aim in this study was to
      analyze if changes in body weight and other nutritional parameters are influenced
      by the illnesses presented during hospitalization. PATIENTS AND METHODS: Over a
      period of three years, we retrospectively chose chronic haemodialysis patients
      that were admitted for more than four days, excluding those cases that died in
      the hospital. We randomly chose one admission episode per patient so as to avoid
      excessive weighing of repeated admissions. We took data concerning weight
      changes, pre-admission and post-discharge analytical results, analytical results
      following first week of hospital stay, disorders causing hospital admission and
      those that developed during the hospital stay. We created a point score system to
      record the total of illnesses presented. RESULTS: The study included 77 patients,
      aged 67+/-12 years and having undergone haemodialysis for 31+/-34 months.
      Hospital stay was 17.8+/-12.6 days (median, 12 days). We observed that many
      patients admitted for digestive and osteoarticular disorders, heart failure or
      coronary syndrome lost more weight during their hospital stay, although no
      significant differences were reached. The total number of disorders suffered
      during the hospital stay was independent of the cause of hospitalisation.
      Anaemia,heart arrhythmias and signs of heart failure were associated with longer
      hospital stays, however it was only anaemia that was significantly related to
      greater weight loss. Weight loss was not related to surgery or infections.
      Albumin levels during the first week of hospital stay were different depending on
      the disorder upon admission. It was lower when the patients were admitted for
      digestive disorders (ANOVA, P=.05). Changes in albumin and creatinine levels
      before and after the hospital stay did not differ among disorders. We observed a
      relationship between having presented with more disorders during the stay and a
      longer stay, lower initial albumin and greater weight loss following discharge.
      In the multivariate analysis, we found the following weight loss predictors:
      stay, anaemia, and sepsis. We also found the following hospital stay
      predictors:Charlson's comorbidity index, heart arrhythmias, anaemia, sepsis and
      surgery. CONCLUSIONS: Malnutrition during the hospital stay depends on the
      duration and the number of disorders that develop during this time, the cause of
      admission having less impact on this. Albumin levels decrease earlier in patients
      that are going to develop more disorders during hospital stay.

PMID- 21738251
TI  - Acute renal failure in patient treated with anti-tumour necrosis factor alpha.

PMID- 21738252
TI  - Chronic pulmonary bleeding as the first sign of microscopic polyangiitis
      associated with autoimmune thyroiditis.

PMID- 21738253
TI  - Purple urine.

PMID- 21738254
TI  - Hepatic venous pressure gradient and transjugular liver biopsy to assess patients
      with kidney failure and chronic liver disease.

PMID- 21738255
TI  - Acute kidney failure in the context of a Tako-Tsubo syndrome.

PMID- 21738256
TI  - Mushroom poisoning: Orellanus syndrome.

PMID- 21738257
TI  - Hepatotoxicity following cyclophosphamide treatment in a patient with MPO-ANCA
      vasculitis.

PMID- 21738258
TI  - Syndrome of inappropriate antidiuretic hormone hypersecretion associated with
      Guillain-Barre syndrome.

PMID- 21738259
TI  - Giant pseudoaneurysm of an autologous arteriovenous fistula in the forearm:
      surgical repair.

PMID- 21738260
TI  - Rhabdomyolysis secondary to hyponatraemia.

PMID- 21738261
TI  - Rituximab therapy for Wegener's granulomatosis refractory to conventional
      treatment.

PMID- 21738262
TI  - Optimization of a LSO-Based Detector Module for Time-of-Flight PET.
AB  - We have explored methods for optimizing the timing resolution of an LSO-based
      detector module for a single-ring, "demonstration" time-of-flight PET camera. By
      maximizing the area that couples the scintillator to the PMT and minimizing the
      average path length that the scintillation photons travel, a single detector
      timing resolution of 218 ps fwhm is measured, which is considerably better than
      the ~385 ps fwhm obtained by commercial LSO or LYSO TOF detector modules. We
      explored different surface treatments (saw-cut, mechanically polished, and
      chemically etched) and reflector materials (Teflon tape, ESR, Lumirror, Melinex,
      white epoxy, and white paint), and found that for our geometry, a chemically
      etched surface had 5% better timing resolution than the saw-cut or mechanically
      polished surfaces, and while there was little dependence on the timing resolution
      between the various reflectors, white paint and white epoxy were a few percent
      better. Adding co-dopants to LSO shortened the decay time from 40 ns to ~30 ns
      but maintained the same or higher total light output. This increased the initial
      photoelectron rate and so improved the timing resolution by 15%. Using
      photomultiplier tubes with higher quantum efficiency (blue sensitivity index of
      13.5 rather than 12) improved the timing resolution by an additional 5%. By
      choosing the optimum surface treatment (chemically etched), reflector (white
      paint), LSO composition (co-doped), and PMT (13.5 blue sensitivity index), the
      coincidence timing resolution of our detector module was reduced from 309 ps to
      220 ps fwhm.

PMID- 21738263
TI  - Help to Family and Friends: Are There Gender Differences at Older Ages?
AB  - This paper uses recent data from the Wisconsin Longitudinal Study (N = 5,220) to
      explore gender differences in the extent to which adults in their 50s and 60s
      provide informal help to their adult children, elderly parents and friends We
      find that both men and women report very high levels of helping kin and nonkin
      alike, though women do more to assist elderly parents and women provide much more
      emotional support to others than do men. Men provide more assistance than do
      women with "housework, yard work and repairs." As they retire from the workforce,
      married men become significantly more involved in the care of their
      grandchildren, virtually eliminating any gender difference by the time they are
      in their 60s.

PMID- 21738264
TI  - Atg3-mediated lipidation of Atg8 is involved in encystation of Acanthamoeba.
AB  - Autophagy is a catabolic process involved in the degradation of a cell's own
      components for cell growth, development, homeostasis, and the recycling of
      cellular products. Autophagosome is an essential component in the protozoan
      parasite during differentiation and encystation. The present study identified and
      characterized autophagy-related protein (Atg) 3, a member of Atg8 conjugation
      system, in Acanthamoeba castellanii (AcAtg3). AcAtg3 encoding a 304 amino acid
      protein showed high similarity with the catalytic cysteine site of other E2 like
      enzymes of ubiquitin system. Predicted 3D structure of AcAtg3 revealed a hammer
      like shape, which is the characteristic structure of E2-like enzymes. The
      expression level of AcAtg3 did not increase during encystation. However, the
      formation of mature cysts was significantly reduced in Atg3-siRNA transfected
      cells in which the production of Atg8-phosphatidylethanolamine conjugate was
      inhibited. Fluorescent microscopic analysis revealed that dispersed AcAtg3-EGFP
      fusion protein gathered around autophagosomal membranes during encystation. These
      results provide important information for understanding autophagic machinery
      through the lipidation reaction mediated by Atg3 in Acanthamoeba.

PMID- 21738265
TI  - Pro-inflammatory cytokine expression of spleen dendritic cells in mouse
      toxoplasmosis.
AB  - Dendritic cells have been known as a member of strong innate immune cells against
      infectious organelles. In this study, we evaluated the cytokine expression of
      splenic dendritic cells in chronic mouse toxoplasmosis by tissue cyst-forming
      Me49 strain and demonstrated the distribution of lymphoid dendritic cells by
      fluorescence-activated cell sorter (FACS). Pro-inflammatory cytokines, such as IL
      1alpha, IL-1beta, IL-6, and IL-10 increased rapidly at week 1 post-infection (PI)
      and peaked at week 3 PI. Serum IL-10 level followed the similar patterns. FACS
      analysis showed that the number of CD8alpha(+)/CD11c(+) splenic dendritic cells
      increased at week 1 and peaked at week 3 PI. In conclusion, mouse splenic
      dendritic cells showed early and rapid cytokine changes and may have important
      protective roles in early phases of murine toxoplasmosis.

PMID- 21738266
TI  - Immune responses of mice intraduodenally infected with Toxoplasma gondii KI-1
      tachyzoites.
AB  - Toxoplasma gondii Korean isolate (KI-1) tachyzoites were inoculated
      intraduodenally to BALB/c mice using a silicon tube, and the course of infection
      and immune responses of mice were studied. Whereas control mice, that were
      infected intraperitoneally, died within day 7 post-infection (PI), the
      intraduodenally infected mice survived until day 9 PI (infection with 1 * 10(5)
      tachyzoites) or day 11 PI (with 1 * 10(6) tachyzoites). Based on histopathologic
      (Giemsa stain) and PCR (B1 gene) studies, it was suggested that tachyzoites,
      after entering the small intestine, invaded into endothelial cells, divided
      there, and propagated to other organs. PCR appeared to be more sensitive than
      histopathology to detect infected organs and tissues. The organisms spread over
      multiple organs by day 6 PI. However, proliferative responses of splenocytes and
      mesenteric lymph node (MLN) cells in response to con A or Toxoplasma lysate
      antigen decreased significantly, suggesting immunosuppression. Splenic CD4(+) and
      CD8(+) T-lymphocytes showed decreases in number until day 9 PI, whereas IFN-gamma
      and IL-10 decreased slightly at day 6 PI and returned to normal levels by day 9
      PI. No TNF-alpha was detected throughout the experimental period. The results
      showed that intraduodenal infection with KI-1 tachyzoites was successful but did
      not elicit significant mucosal immunity in mice and allowed dissemination of T.
      gondii organisms to systemic organs. The immunosuppression of mice included
      reduced lymphoproliferative responses to splenocytes and MLN cells to mitogen and
      low production of cytokines, such as IFN-gamma, TNF-alpha, and IL-10, in response
      to T. gondii infection.

PMID- 21738267
TI  - Plasmodium vivax dhfr mutations among isolates from malarious areas of Iran.
AB  - The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is
      uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP
      because of mixed infections with other Plasmodium species. As P. vivax is the
      most prevalent species of human malaria parasites in Iran, monitoring of
      resistance of the parasite against the drug is necessary. In the present study,
      50 blood samples of symptomatic patients were collected from 4 separated
      geographical regions of south-east Iran. Point mutations at residues 57, 58, 61,
      and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R,
      117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found
      in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61
      was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated.
      The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%).
      Haplotypes with 3 and 4 point mutations were not found. The present study
      suggested that P. vivax in Iran is under the pressure of SP and the sensitivity
      level of the parasite to SP is diminishing and this fact must be considered in
      development of malaria control programs.

PMID- 21738268
TI  - Hematological and serum biochemical analyses in experimental caprine
      besnoitiosis.
AB  - This study was undertaken to investigate the hematological and biochemical
      changes in experimentally infected goats with Besnoitia caprae from the time of
      infection till 360 days post-infection (PI). Six male goats were inoculated
      subcutaneously with 13 * 10(7) bradyzoites of B. caprae, and blood samples were
      collected from the jugular vein. The total erythrocyte and total leukocyte
      counts, hematocrit value, and differential leukocyte counts were determined.
      Serum biochemical analysis, including the total protein, albumin, total globulin,
      cholesterol, triglyceride, chloride, testosterone, calcium (Ca(2+)), inorganic
      phosphorus, sodium (Na(+)), potassium (K(+)), iron (Fe(2+)), glucose, serum
      amyloid A (SAA), haptoglobin (Hp), fibrinogen, ceruloplasmin, aspartate
      aminotransferase, alanine aminotransferase, creatine kinase, lactate
      dehydrogenase, and alkaline phosphatase, was undertaken. Skin biopsy from the
      limbs were collected at weekly intervals and histologically examined for
      Besnoitia cysts. Cysts were present in the skin biopsies of the leg of the
      infected goats from day 28 PI. There were variations in hematological analyses,
      but no significant difference was seen. From day 30 to 360 PI, results showed
      that SAA, Hp, fibrinogen, and ceruloplasmin concentrations increased, whereas
      testosterone concentrations decreased. Infected goats exhibited decrease of
      albumin and increase of serum total protein and globulin concentrations. By
      contrast, there were no significant differences in the remained analyses
      concentrations.

PMID- 21738269
TI  - Seroprevalence of antibodies against Anisakis simplex larvae among health
      examined residents in three hospitals of southern parts of Korea.
AB  - The present study was performed to estimate the seroprevalence of larval Anisakis
      simplex infection among the residents health-examined in 3 hospitals in southern
      parts of Korea. A total of 498 serum samples (1 serum per person) were collected
      in 3 hospitals in Busan Metropolitan city, Masan city, and Geoje city in
      Gyeongsangnam-do (Province) and were examined by IgE-ELISA and IgE-western
      blotting with larval A. simplex crude extract and excretory-secretory products
      (ESP). The prevalence of antibody positivity was 5.0% and 6.6% with ELISA against
      crude extracts and ESP, respectively. It was also revealed that infection
      occurred throughout all age groups and higher in females than in males. A
      specific protein band of 130 kDa was detected from 10 patients with western blot
      analysis against crude extract and ESP among those who showed positive results by
      ELISA. Our study showed for the first time the seroprevalence of anisakiasis in
      Korea. The allergen of 130 kDa can be a candidate for serologic diagnosis of
      anisakiasis.

PMID- 21738270
TI  - Comparative efficacy of ivermectin and levamisole for reduction of migrating and
      encapsulated larvae of Baylisascaris transfuga in mice.
AB  - The comparative efficacy of 2 anthelmintics (ivermectin and levamisole) against
      Baylisascaris transfuga migrating and encapsulated larvae was studied in mice. A
      total of 60 BALB/c mice inoculated each with about 1,000 embryonated B. transfuga
      eggs were equally divided into 6 groups (A-F) randomly. Mice of groups A and B
      were treated with ivermectin and levamisole, respectively, on day 3 post
      infection (PI). Mice of groups A-C were killed on day 13 PI. Similarly, groups D
      and E were treated with ivermectin and levamisole, respectively, on day 14 PI,
      and all mice of groups D-F were treated on day 24 PI. The groups C and F were
      controls. Microexamination was conducted to count the larvae recovering from each
      mouse. The percentages of reduction in the number of migrating larvae recovered
      from group A (ivermectin) and B (levamisole) were 88.3% and 81.1%, respectively.
      In addition, the reduction in encapsulated larvae counts achieved by ivermectin
      (group D) and levamisole (group E) was 75.0% and 49.2%, respectively. The results
      suggested that, to a certain extent, both anthelmintics appeared to be more
      effective against migrating larvae than encapsulated larvae. However, in the
      incipient stage of infection, ivermectin may be more competent than levamisole as
      a larvicidal drug for B. transfuga.

PMID- 21738271
TI  - Assessment of loiasis and outcomes of ivermectin masstreatment in Ijebu-North,
      Nigeria.
AB  - A total of 286 individuals from 3 selected communities (Areedi-Aje,
      Ipakodo/Ojokodo, and Ijebu-Igbo) of Ijebu-North, southwestern Nigeria were
      examined for Loa loa microfilaremia using finger prick blood smear, between
      December 2008 and March 2009. Rapid assessment procedure for loiasis (RAPLOA) was
      used to obtain information, from 187 Ijebu-Igbo residents, on adverse reactions
      experienced from retrospective treatments with ivermectin and history of eye
      worm. Only 33.9% of the respondents reported having had a history of eye worm
      while 33.2% had microfilaremia. The demographic factor of gender was not
      significant determinants of the prevalence (P>0.05) while age was significant
      (P<0.05). The highest prevalence of eye worm history and microfilaremia were
      recorded in 61-70 and 15-20 years of age categories, respectively. Ijebu-Igbo had
      27.3% eye worm history, 32.1% microfilaremia, and the highest intensity of 140
      microfilariae (mf)/ml. Ipakodo area had the highest eye worm history of 54.4% and
      the highest intensity of 420 mf/ml. Areedi-Aje had the highest occurrence of
      45.2% microfilaremia and the highest intensity of 460 mf/ml. Predictably, Areedi
      Aje and Ipakodo areas were high risk communities. The low intensity of L. loa
      infection with an insignificant (2.1%; P>0.05) adverse reactions from 187
      subjects involved in the retrospective ivermectin administration confirmed that
      ivermectin delivery may be considered safe. The community-directed treatment with
      ivermectin (CDTI) programme was most probably responsible for the low prevalence
      and intensity.

PMID- 21738272
TI  - Prevalence of Metagonimus metacercariae in sweetfish, Plecoglossus altivelis,
      from eastern and southern coastal areas in Korea.
AB  - The present study was performed to determine the current infecion status of
      Metagonimus yokogawai metacercariae in sweetfish, Plecoglossus altivelis,
      collected from several streams in eastern and southern coastal areas of Korea.
      The sweetfish collected were artificially digested with pepsin-HCl solution and
      examined under a stereomicroscope in August and September, 2007. Out of 145
      sweetfish collected from 10 streams in eastern coasts (Gangwon-do and Gye
      ongsangbuk-do), 88 (60.7%) were infected with Metagonimus metacercariae. The
      average metacercarial density was 61 per infected fish. Among 141 sweetfish
      collected from 10 streams in southern coasts (Gyeongsangnam-do, Ulsan
      Metropolitan city, and Jeollanam-do), 140 (99.3%) were infected with Metagonimus
      metacercariae, and their average density was 949 per infected fish. The present
      study confirmed that M. yokogawai metacercariae are still prevalent in the
      sweetfish from several eastern and southern coastal localities. The prevalence
      and metacercarial density were much higher in the sweetfish from streams of
      southern coasts than in those of eastern coasts. Therefore, attention should be
      paid to this small fluke infection, and consumption of raw sweetfish naturally
      produced in these areas should be prohibited.

PMID- 21738273
TI  - Clinical features of ocular toxoplasmosis in Korean patients.
AB  - We report here the records of 10 consecutive Korean patients (10 eyes) with
      ocular toxoplasmosis which showed the typical clinical manifestations with
      seropositivity for Toxoplasma gondii specific IgG antibodies by micro-ELISA
      between 2006 and 2010. Nine patients were males and 1 was female; their age was
      50.5 +/- 13.8 years. The most common accompanying signs were vitritis (100%),
      anterior uveitis (70%), and scattered white deposit (80%). Pre-existing
      retinochoroidal scar was found in 1 (10%) patient. All patients received
      antiparasitic chemotherapy and systemic corticosteroid treatment, which resolved
      the presenting attack and recovered the visual acuity better than initial one in
      9 patients and worse in 1. Optic atrophy, cataract, and retinal
      neovascularization were observed during the follow-up period and recurrence was
      detected in 3 eyes (30%) 6 to 20 months after the initial attack. In Korea,
      although rarely detected and reported, ocular toxoplasmosis needs more attention
      in clinical field of retinal diseases.

PMID- 21738274
TI  - Ophthalmomyiasis caused by a Phormia sp. (Diptera: Calliphoridae) larva in an
      enucleated patient.
AB  - Ophthalmomyiasis rarely occurs worldwide, and has not been reported in Korea. We
      present here a case of ophthalmomyiasis caused by Phormia sp. fly larva in an
      enucleated eye of a patient. In June 2010, a 50-year-old man was admitted to
      Dankook University Hospital for surgical excision of a malignant melanoma located
      in the right auricular area. He had a clinical history of enucleation of his
      right eye due to squamous cell carcinoma 5 years ago. During hospitalization,
      foreign body sensation developed in his right eye, and close examination revealed
      a fly larva inside the eye, which was evacuated. The larva was proved to be
      Phormia sp. based on the morphology of the posterior spiracle. Subsequently, no
      larva was found, and the postoperative course was uneventful without any
      complaints of further myiasis. This is the first case of ophthalmomyiasis among
      the literature in Korea, and also the first myiasis case caused by Phormia sp. in
      Korea.

PMID- 21738275
TI  - Calpains are involved in Entamoeba histolytica-induced death of HT-29 colonic
      epithelial cells.
AB  - Entamoeba histolytica is an enteric tissue-invading protozoan parasite that can
      cause amebic colitis and liver abscess in humans. E. histolytica has the
      capability to kill colon epithelial cells in vitro; however, information
      regarding the role of calpain in colon cell death induced by ameba is limited. In
      this study, we investigated whether calpains are involved in the E. histolytica
      induced cell death of HT-29 colonic epithelial cells. When HT-29 cells were co
      incubated with E. histolytica, the propidium iodide stained dead cells markedly
      increased compared to that in HT-29 cells incubated with medium alone. This pro
      death effect induced by ameba was effectively blocked by pretreatment of HT-29
      cells with the calpain inhibitor, calpeptin. Moreover, knockdown of m- and u
      calpain by siRNA significantly reduced E. histolytica-induced HT-29 cell death.
      These results suggest that m- and u-calpain may be involved in colon epithelial
      cell death induced by E. histolytica.

PMID- 21738276
TI  - Prevalence of Toxocara canis in dogs, North West Bank of Palestine.
AB  - This study was performed to investigate the prevalence of Toxocara canis in local
      districts in North West Bank of Palestine. Fecal samples from 132 dogs were
      collected in Nablus, Tulkarm, and Jenin cities from September 2008 to April 2009
      and examined for T. canis eggs with the floating technique. The overall infection
      rate of toxocariasis in dogs was 36.4%. The dogs less than 6 months old showed
      higher infection rates than those older than 12 months (P=0.04). Vigorous
      interventions are necessary, such as routine coprological examinations of dogs
      and prescription of anthelmintics to infected dogs.

PMID- 21738277
TI  - Prevalence of Enterobius vermicularis among preschool children in Gimhae-si,
      Gyeongsangnam-do, Korea.
AB  - The present study was performed to determine the prevalence of Enterobius
      vermicularis among preschool children in Gimhae-si, Korea. A total of 6,921
      preschool children in 76 kindergartens were examined using the cellotape perianal
      swab method. The overall egg positive rate (EPR) was 10.5%. The EPR in boys was
      higher than that in girls (adjusted odds ratio [AOR]: 1.5, P<0.001), and it was
      higher in rural than in urban children (AOR: 1.2, P=0.022). The present study
      confirmed that the prevalence of E. vermicularis infection is fairly high among
      preschool children in Gimhae-si. Therefore, systematic control and preventive
      measures should be adopted to reduce morbidity associated with this nematode
      infection.

PMID- 21738279
TI  - Expression of TNF-alpha and IL-1beta in splenic dendritic cells and their serum
      levels in mouse sparganosis.
AB  - Sparganosis is a tissue invading helminthiasis infecting intermediate hosts,
      including humans. Strong immune responses are expected to occur in early phases
      of infection. Thus, we investigated cytokine expressions in splenic dendritic
      cells and in sera after experimental infection of mice. In splenic dendritic
      cells, TNF-alpha and IL-1beta expression peaked at week 1 and week 3 post
      infection (PI), respectively, and also early phase (week 2 PI) depressed cytokine
      expression was noticed. Serum IL-1beta concentration increased significantly at
      week 2 PI and peaked at week 6 PI, and that of TNF-alpha peaked at week 6 PI.
      These results showed that pro-inflammatory cytokines, TNF-alpha and IL-1beta, are
      chronologically regulated in mouse sparganosis.

PMID- 21738278
TI  - Echinostoma ilocanum infection in Oddar Meanchey Province, Cambodia.
AB  - Fecal examinations using the Kato Katz technique were performed on a total of
      1,287 villagers (945 students and 342 general inhabitants) of Oddar Meanchey
      Province, Cambodia in May 2007 and November 2009. The overall intestinal helminth
      egg positive rate was 23.9%, and the most prevalent helminth species was
      hookworms (21.6%). Other helminth eggs detected included echinostomes (1.0%),
      Enterobius vermicularis (0.8%), small trematode eggs (0.7%), which may include
      Opisthorchis viverrini and Haplorchis spp., and Hymenolepis nana (0.4%). In order
      to recover adult echinostomes, we treated 2 patients with 10-15 mg/kg
      praziquantel and purged. Total 14 adult echinostomes, 1 and 13 worms from each
      patient, were collected. The echinostomes characteristically had 49-51 collar
      spines and 2 round or slightly lobated testes. They were identified as
      Echinostoma ilocanum (Garrison, 1908) Odhner, 1911. So far as literature are
      concerned, this is the first record on the discovery of human E. ilocanum
      infection in Cambodia.

PMID- 21738280
TI  - Molecular identification of Taenia tapeworms by Cox1 gene in Koh Kong, Cambodia.
AB  - We collected fecal samples from 21 individuals infected with Taenia tapeworms in
      Koh Kong Province, Cambodia, and performed nucleotide sequencing of the cox1 gene
      and multiplex PCR on the eggs for DNA differential diagnosis of human Taenia
      tapeworms. Genomic DNA was extracted from the eggs of a minimum number of 10
      isolated from fecal samples. Using oligonucleotide primers Ta7126F, Ts7313F,
      Tso7466F, and Rev7915, the multiplex PCR assay proved useful for differentially
      diagnosing Taenia solium, Taenia saginata, and Taenia asiatica based on 706, 629,
      and 474 bp bands, respectively. All of the Taenia specimens from Kho Kong,
      Cambodia, were identified as either T. saginata (n=19) or T. solium (n=2) by cox1
      sequencing and multiplex PCR.

PMID- 21738281
TI  - Understanding neighbourhoods, communities and environments: new approaches for
      social work research.
AB  - This article discusses some new ways in which social work research can explore
      the interaction between neighbourhoods and child and adult wellbeing. The authors
      note that social work practices are often criticised for taking an
      individualistic approach and paying too little attention to the service user's
      environment. The article uses examples of research projects from Chile, the
      United States of America and Wales, to discuss the use of spatially oriented
      research methods for understanding neighbourhood factors. Quantitative,
      qualitative and mixed methods approaches that are particularly appropriate for
      investigating social work relevant topics are discussed in turn, including
      quantitative and qualitative uses for geographical information systems (GIS),
      hierarchical linear modelling (HLM) for analysing spatially clustered data and
      qualitative mobile interviews. The article continues with a discussion of the
      strengths and limitations of using spatially orientated research designs in
      social work research settings and concludes optimistically with suggestions for
      future directions in this area.

PMID- 21738282
TI  - Sharp Quadratic Majorization in One Dimension.
AB  - Majorization methods solve minimization problems by replacing a complicated
      problem by a sequence of simpler problems. Solving the sequence of simple
      optimization problems guarantees convergence to a solution of the complicated
      original problem. Convergence is guaranteed by requiring that the approximating
      functions majorize the original function at the current solution. The leading
      examples of majorization are the EM algorithm and the SMACOF algorithm used in
      Multidimensional Scaling. The simplest possible majorizing subproblems are
      quadratic, because minimizing a quadratic is easy to do. In this paper quadratic
      majorizations for real-valued functions of a real variable are analyzed, and the
      concept of sharp majorization is introduced and studied. Applications to logit,
      probit, and robust loss functions are discussed.

PMID- 21738283
TI  - Thoughts on Rethinking Response to Intervention With Secondary Students.

PMID- 21738286
TI  - ANTIVIRAL COMPOUNDS IN THE PIPELINE TO TACKLE H1N1 INFLUENZA INFECTION.
AB  - The recent pandemic of H1N1 has demonstrated the potential vulnerability of the
      human population to novel influenza viruses. While there is recent increased
      interest and effort in developing effective anti-influenza agents, few new
      products have entered clinical studies. This review will highlight the limited
      armamentarium of licensed influenza agents, and discuss novel compounds and
      strategies that have entered clinical studies and may therefore be imminently
      available to the treating clinician.

PMID- 21738287
TI  - Perception of Wordlikeness: Effects of Segment Probability and Length on the
      Processing of Nonwords.
AB  - A probabilistic phonotactic grammar based on the probabilities of the
      constituents contained in a dictionary of English was used to generate
      multisyllabic nonwords. English-speaking listeners evaluated the wordlikeness of
      these patterns. Wordlikeness ratings were higher for nonwords containing high
      probability constituents and were also higher for nonwords with fewer syllables.
      Differences in the processing of these same nonwords that partially reflected
      their perceived wordlikeness were also found in a recognition memory task.
      Nonwords with higher probability constituents yielded better recognition memory
      performance, suggesting that participants were able to use their knowledge of
      frequently occurring lexical patterns to improve recognition. These results
      suggest that lexical patterns provide the foundation of an emergent phonological
      competence used to process nonwords in both linguistic and metalinguistic tasks.

PMID- 21738288
TI  - Effect of tacrolimus on survival in hepatitis C-infected patients after liver
      transplantation.
AB  - The observation that cyclosporine inhibits HCV replication in vitro has led some
      programs to use cyclosporine as the calcineurin inhibitor (CNI) of choice after
      orthotopic liver transplantation (OLT). Previous studies comparing outcomes with
      different CNIs used small HCV cohorts or had short-term follow-up. We examined
      patient survival and fibrosis progression in all HCV-infected adult primary OLT
      recipients from 1995 to 2004 at the Annette C. and Harold C. Simmons Transplant
      Institute (n = 516). Patients were categorized by their CNI on day 7 post-OLT,
      and they were excluded if they died before day 14. Patient and donor age, sex,
      race, and prevalence of cytomegalovirus infection post-OLT were similar in the
      tacrolimus and cyclosporine patients. As expected, acute cellular rejection and
      steroid-resistant rejection were less common in tacrolimus-treated patients.
      Although no difference in 1-year survival was seen, tacrolimus patients (n = 268)
      had superior 5-year survival compared to cyclosporine patients (n = 248) (75% vs.
      67%; P = 0.02). Fibrosis progression was no different between the groups. In our
      retrospective analysis of 516 post-OLT patients, tacrolimus improved long-term
      survival compared to cyclosporine in HCV-infected patients, although it did not
      impact HCV fibrosis progression.

PMID- 21738289
TI  - The AmBulatory Closure Device Percutaneous Intervention (ABCD-PCI) study: a
      single-center experience.
AB  - The AmBulatory Closure Device Percutaneous Intervention (ABCD-PCI) study is a
      multicenter randomized prospective controlled trial evaluating the safety of and
      patient satisfaction with same-day discharge following ambulatory percutaneous
      intervention with a closure device. This article reviews the findings from a
      single center, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, from
      October 2008 through April 2010, with 23 patients in the same-day discharge group
      and 21 patients in the next-day discharge group. There were no differences
      between the groups in demographic or procedure characteristics. Outcomes were
      measured by a questionnaire and 7-day and 30-day follow-up phone calls. Results
      showed that same-day discharge after percutaneous intervention with a closure
      device is as safe as next-day discharge. However, there was a trend for a higher
      comfort level among patients in the next-day discharge group.

PMID- 21738290
TI  - Splenic abscess and multiple brain abscesses caused by Streptococcus intermedius
      in a young healthy man.
AB  - We report a case of splenic abscess with multiple brain abscesses caused by
      Streptococcus intermedius in a healthy young man without any identifiable risk
      factors, which resolved with percutaneous drainage and antibiotics. Streptococcus
      intermedius, a member of the Streptococcus anginosus group, is a common commensal
      organism of the oral cavity and gastrointestinal tract, and it is a known cause
      of deep-seated infections. Suppurative infections caused by Streptococcus
      anginosus group are sometimes associated with bacteremia, but hematogenous spread
      of infection from an occult source leading to concurrent splenic abscess and
      multiple brain abscesses has never been previously reported in a healthy young
      individual.

PMID- 21738291
TI  - Evaluation of the SEDline to improve the safety and efficiency of conscious
      sedation.
AB  - Brain function monitors have improved safety and efficiency in general
      anesthesia; however, they have not been adequately tested for guiding conscious
      sedation for periodontal surgical procedures. This study evaluated the patient
      state index (PSI) obtained from the SEDline monitor (Sedline Inc., San Diego, CA)
      to determine its capacity to improve the safety and efficiency of intravenous
      conscious sedation during outpatient periodontal surgery. Twenty-one patients at
      the periodontics clinic of Baylor College of Dentistry were admitted to the study
      in 2009 and sedated to a moderate level using midazolam and fentanyl during
      periodontal surgery. The PSI monitoring was blinded from the clinician, and the
      following data were collected: vital signs, Ramsay sedation scale (RSS),
      medications administered, adverse events, PSI, electroencephalography, and the
      patients' perspective through visual analogue scales. The data were correlated to
      evaluate the PSI's ability to assess the level of sedation. Results showed that
      the RSS and PSI did not correlate (r = -0.25) unless high values associated with
      electromyographical (EMG) activity were corrected (r = -0.47). Oxygen
      desaturation did not correlate with the PSI (r = -0.08). Satisfaction (r = -0.57)
      and amnesia (r = -0.55) both increased as the average PSI decreased. In
      conclusion, within the limits of this study, PSI appears to correlate with
      amnesia, allowing a practitioner to titrate medications to that effect. It did
      not provide advance warning of adverse events and had inherent inaccuracies due
      to EMG activity during oral surgery. The PSI has the potential to increase safety
      and efficiency in conscious sedation but requires further development to
      eliminate EMG activity from confounding the score.

PMID- 21738292
TI  - Effectiveness and safety of transradial artery access for cardiac
      catheterization.
AB  - The transradial approach for coronary angiography and angioplasty, while not new,
      is gaining momentum again as a viable alternative to the transfemoral approach.
      While technically it may have some challenges, there are significant benefits
      including reduced patient discomfort, improved time to ambulation, reduction in
      costs, and reduction in potentially life-threatening complications. The technique
      is not difficult to learn, and the equipment is similar to that used in more
      traditional approaches. To expand awareness of this method, this article
      discusses the history of the technique, reviews the data comparing it to the more
      widely used transfemoral technique, and discusses some of the experience at
      Baylor University Medical Center at Dallas, where this approach has been gaining
      popularity.

PMID- 21738293
TI  - Utility of pattern recognition in the detection of unsuspected additional primary
      malignancies on positron emission tomography-computed tomography.
AB  - Positron emission tomography-computed tomography (PET-CT) has been shown to
      detect unexpected synchronous malignancies in up to 4.8% of patients and has been
      shown to be more sensitive than conventional staging alone. Detection of an
      unsuspected synchronous malignancy on PET-CT will often affect both patient
      treatment and prognosis. This article reviews expected patterns of disease spread
      so that a synchronous malignancy can be more easily recognized.

PMID- 21738294
TI  - Operative management of pulmonary abscess due to spontaneous perforation of
      diffuse intramural esophageal pseudodiverticulosis.
AB  - Diffuse intramural esophageal pseudodiverticulosis is a rare, benign esophageal
      condition of unclear cause, pathologically manifested by pseudodiverticula along
      a portion of the esophagus. It most commonly presents as dysphagia and is usually
      amenable to endoscopic dilation. It is most reliably diagnosed endoscopically or
      with a fluoroscopic swallow study. Surgical intervention is rarely indicated but
      can create a need for an extensive resection and reconstruction, as in the case
      presented here.

PMID- 21738295
TI  - Primary hyperparathyroidism and pregnancy.
AB  - Primary hyperparathyroidism is the third most common endocrine disorder after
      diabetes and thyroid disease, and women are affected twice as often as men.
      Hyperparathyroidism in pregnancy was first reported in 1931. Maternal
      complications in patients with hyperparathyroidism can be as high as 67%. We
      present a case of a pregnant patient with chronic hypertension that was
      exacerbated throughout the course of her pregnancy with a concomitant diagnosis
      of primary hyperparathyroidism and its sequelae for both the mother and fetus.

PMID- 21738296
TI  - Unraveling the conflicts to preserve research integrity.

PMID- 21738297
TI  - Can Osler teach us about 21st-century medical ethics?

PMID- 21738299
TI  - Gene therapy: available now!

PMID- 21738298
TI  - William Henry Welch (1850-1934): the road to Johns Hopkins.
AB  - William Henry Welch's selection in 1884 as the first faculty member of the new
      medical school at Johns Hopkins created the invigorating atmosphere that
      generated the revolutionary changes in medical training and laboratory medicine
      that transformed medicine in America. Dr. Welch's family traditions, his New
      England upbringing, Yale education, and German university experience prepared a
      unique individual to lead American medicine into the 20th century.

PMID- 21738300
TI  - Nurturing your divine feminine.

PMID- 21738301
TI  - Lillian Carter, Rosalynn Carter, and caregiving.

PMID- 21738302
TI  - Extranodal NK/T-cell lymphoma, nasal type.
AB  - We report a case of extranodal NK/T-cell lymphoma, nasal type, which is rare in
      the United States and Europe. It is more prevalent in Asians and Native Americans
      of Mexico, Central America, and South America. A 30-year-old Southeast Asian man
      with facial swelling, fever, and unintentional weight loss was found to have
      leukopenia and thrombocytopenia. He underwent endoscopic sinus surgery, which
      confirmed extranodal NK/T-cell lymphoma, nasal type, and a blood and bone marrow
      examination, which was negative for involvement but yielded the diagnosis of
      alpha-E thalassemia. The patient received chemotherapy, radiotherapy, and a stem
      cell transplant with 100% engraftment.

PMID- 21738303
TI  - Electrocardiogram in a woman with cor pulmonale.

PMID- 21738304
TI  - Recombinant tissue plasminogen activator for the treatment of acute ischemic
      stroke.
AB  - The use of recombinant tissue plasminogen activator (rtPA) has been the standard
      of care for treatment of acute ischemic stroke for several years. Studies
      evaluating the efficacy, safety, and optimal timing of rtPA use are ongoing.
      Recently, results of new studies led to expansion of the short timeframe from
      stroke symptom onset in which a patient can receive this treatment. Additionally,
      more data are available to support the current goals of administration of rtPA to
      eligible patients as quickly as possible, as earlier treatment has been proven to
      improve outcomes.

PMID- 21738305
TI  - Considerations in treating patients with chronic pain.

PMID- 21738306
TI  - Facts and ideas from anywhere.

PMID- 21738307
TI  - Modeling the mitochondrial dysfunction in neurogenerative diseases due to high H+
      concentration.
AB  - Considering the latest researches, disruptions in the regulation of mitochondrial
      dynamics, low energy production, increased reactive oxygen species and mtDNA
      damage are relevant to human diseases, mainly in neurogenerative diseases and
      cancer. This article represents inner mitochondrial membrane as a natural
      superconductor giving also the corresponding mathematical model; nevertheless the
      creation of electric complexes into the inner mitochondrial membrane due to the
      unusual concentration of protons disrupts the normal flow of electrons and the
      production of ATP. Therefore, we propose the term 'electric thromboses' for the
      explanation of these inadequate electrons' flow, presenting simultaneously a
      natural mechanism of this important and unique phenomenon.

PMID- 21738308
TI  - Identification of EPAC (Exchange Protein Activated by cAMP) bioinformatically as
      a potential signalling biomarker in Cardiovascular Disease (CVD) and its
      molecular docking by a lead molecule.
AB  - The present work delineates the combinatorial approach of firstly, creation of a
      centralized data-set comprising signalling proteins identified on the basis of
      altered expression, such as over-expression or repression of a set of signalling
      protein(s) leading to the cause of the disease, which is based on published
      reports screened through Pubmed and secondly, in the in silico creation of novel
      lead (drug) molecules and docking of identified signalling biomarkers using such
      drugs to investigate possibility of their future application in the model systems
      eventually. EPAC (Exchange Protein Activated by cAMP) emerges as a signalling
      biomarker in cases studied presently. Brefeldin, the known inhibitor of EPAC,
      though the mechanism yet unexplored, has been the molecule used as the
      pharmacophore for creation of lead drug molecule. Various modifications have been
      incorporated into the pharmacophore to increase the hydrophobic interactions for
      increasing the binding efficiency of the generated lead molecule. Side-chain
      modifications of the pharmacophore and refinement of data through firedock upon
      docking of EPAC with the modified pharmacophore yielded best results on the bases
      of atomic contact energy, van der Waal and partial electrostatic interactions as
      well as additional estimations of the binding free energy. Modifications of CH3
      at C15 with COOH and H at C2 with OH in brefeldin showed the best docking results
      on the basis of protein-drug interaction parameters. The present work provides a
      clue in rational design of EPAC inhibitors which could be developed as drug lead
      in combating CVD.

PMID- 21738309
TI  - Comparison and correlation of Simple Sequence Repeats distribution in genomes of
      Brucella species.
AB  - Computational genomics is one of the important tools to understand the
      distribution of closely related genomes including simple sequence repeats (SSRs)
      in an organism, which gives valuable information regarding genetic variations.
      The central objective of the present study was to screen the SSRs distributed in
      coding and non-coding regions among different human Brucella species which are
      involved in a range of pathological disorders. Computational analysis of the SSRs
      in the Brucella indicates few deviations from expected random models. Statistical
      analysis also reveals that tri-nucleotide SSRs are overrepresented and
      tetranucleotide SSRs underrepresented in Brucella genomes. From the data, it can
      be suggested that over expressed tri-nucleotide SSRs in genomic and coding
      regions might be responsible in the generation of functional variation of
      proteins expressed which in turn may lead to different pathogenicity, virulence
      determinants, stress response genes, transcription regulators and host adaptation
      proteins of Brucella genomes. ABBREVIATIONS: SSRs - Simple Sequence Repeats, ORFs
      - Open Reading Frames.

PMID- 21738310
TI  - HIV associated dementia and HIV encephalitis II: Genes on chromosome 22 expressed
      in individually microdissected Globus pallidus neurons (Preliminary analysis).
AB  - We analyzed RNA gene expression in neurons from 16 cases in four categories, HIV
      associated dementia with HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and
      HIV-1-positive (HIV+)with neither HAD nor HIVE. We produced the neurons by laser
      capture microdissection (LCM) from cryopreserved globus pallidus. Of 55,000 gene
      fragments analyzed, expression of 197 genes was identified with significance (p =
      0.005).We examined each gene for its position in the human genome and found a non
      stochastic occurrence for only seven genes, on chromosome 22. Six of the seven
      genes were identified, CSNK1E (casein kinase 1 epsilon), DGCR8 (Di George
      syndrome critical region 8), GGA1 (Golgi associated gamma adaptin ear containing
      ARF binding protein 1), MAPK11 (mitogen activated protein kinase 11), SMCR7L
      (Smith-Magenis syndrome chromosome region candidate 7-like), andTBC1D22A (TBC1
      domain family member 22A). Six genes (CSNK1E, DGCR8, GGA1, MAPK11, SMCR7L, and
      one unidentified gene) had similar expression profiles across HAD/HIVE, HAD, and
      HIVE vs. HIV+ whereas one gene (TBC1D22A) had a differing gene expression profile
      across these patient categories. There are several mental disease-related genes
      including miRNAs on chromosome 22 and two of the genes (DGCR8 and SMCR7L)
      identified here are mental disease-related. We speculate that dysregulation of
      gene expression may occur through mechanisms involving chromatin damage and
      remodeling. We conclude that the pathogenesis of NeuroAIDS involves dysregulation
      of expression of mental disease-related genes on chromosome 22 as well as
      additional genes on other chromosomes. The involvement of these genes as well as
      miRNA requires additional investigation since numerous genes appear to be
      involved.

PMID- 21738311
TI  - Isolation, identification and computational studies on Pseudomonas aeruginosa sp.
      strain MPC1 in tannery effluent.
AB  - A study about isolation, identification and analysis of bacteria in waste water.
      Here the tannery effluent used as a sample for the entire analysis. A bacterial
      strain, designated MPC1 was isolated from a waste water sample collected from
      tannery effluent, Trichy, India and identified using a molecular approach. On the
      basis of the bacterial 16s rRNA gene sequence phylogeny and comparison of this
      gene sequence with sequence in RNA sequence database, it is considered that
      isolate is closely related to members of the Pseudomonas aeruginosa Sp.
      Phylogenetic and molecular evolutionary analyses were conducted using MEGA.
      Identification of regulatory elements and Transcription Factor with their binding
      sites in 16S rRNA gene of Pseudomonas aeruginosa mpc1 was performed using BPROM
      tool. The sequence of 16s rRNA (Pseudomonas aeruginosa sp MPC 1) is submitted to
      Genbank in NCBI database (Ac.No-JF708077).

PMID- 21738312
TI  - Analysis of glycosylation motifs and glycosyltransferases in Bacteria and
      Archaea.
AB  - The process of glycosylation has been studied extensively in prokaryotes but many
      questions still remain unanswered. Glycosyltransferase is the enzyme which
      mediates glycosylation and has its preference for the target glycosylation sites
      as well as for the type of glycosylation i.e. N-linked and O-linked
      glycosylation. In this study we carried out the bioinformatics analysis of one of
      the key enzymes of pgl locus from Campylobacter jejuni, known as PglB, which is
      distributed widely in bacteria and AglB from archaea. Relatively little sequence
      similarity was observed in the archaeal AglB(s) as compared to those of the
      bacterial PglB(s). In addition we tried to the answer the question of as to why
      not all the sequins Asp-X-Ser/Thr have an equal opportunity to be glycosylated by
      looking at the influence of the neighboring amino acids but no significant
      conserved pattern of the flanking sites could be identified. The software tool
      was developed to predict the potential glycosylation sites in autotransporter
      protein, the virulence factors of gram negative bacteria, and our results
      revealed that the frequency of glycosylation sites was higher in adhesins (a
      subclass of autotransporters) relative to the other classes of autotransporters.

PMID- 21738313
TI  - Variability analyses of functional domains within glucosamine-6-phosphate
      synthase of mycosescausing fungi.
AB  - The immunosuppressive individuals are highly prone to get afflicted with invasive
      opportunistic fungal infections such as Candidiasis, Aspergillosis,
      Histoplasmosis, Coccidioidomycosis, Blastomycosis, Penicilliosis, Cryptococcosis
      and Zygomycosis which are becoming a cause of concern to the mankind due to their
      high morbidity and mortality rates. The existing antifungal agents are not
      completely effective due to their severe side-effects and recurrent drug
      resistance in fungi. Hence, there is an urgent need to develop newer and better
      antifungal drugs. The enzyme Glucosamine-6-phosphate (G-6-P) synthase catalyzes
      the ratelimiting step of the fungal cell-wall biosynthetic pathway and targeting
      it can inhibit the growth of the fungus. The present study attempts to
      investigate the inherent variations in functional domain viz. Glutaminase (GATase
      II) and Sugar Isomerising (SIS) of Glucosamine-6-phosphate (G-6-P) synthase
      enzyme of mycoses-causing fungi. These domains may be identified as probable
      active site(s). Multiple sequence alignment performed using ClustalX2 and
      construction of phylogenetic tree of individual domains by MEGA v5.0 helped in
      the analyses of several variable amino acid sites within the domains suggesting
      their vital role in the pathogenesis of the fungi. Further, the online server
      ConSurf implied that mostly, the highly conserved residues of the domains were
      functional and exposed on the surface of the active site, making it an easy
      target for the drugs. Consequently, variable analysis of functional domains of
      target implicated the importance of target specific drug discovery for the
      treatment of invasive fungal infections or mycoses.

PMID- 21738314
TI  - A heuristic method for discovering biomarker candidates based on rough set
      theory.
AB  - We apply a combined method of heuristic attribute reduction and evaluation of
      relative reducts in rough set theory to gene expression data analysis. Our method
      extracts as many relative reducts as possible from the gene-expression data and
      selects the best relative reduct from the viewpoint of constructing useful
      decision rules. Using a breast cancer dataset and a leukemia dataset, we
      evaluated the classification accuracy for the test samples and biological
      meanings of the rules. As a result, our method presented superior classification
      accuracy comparable to existing salient classifiers. Moreover, our method
      extracted interesting rules including a novel biomarker gene identified in recent
      studies. These results indicate the possibility that our method can serve as a
      useful tool for gene expression data analysis.

PMID- 21738315
TI  - Prediction of N-myristoylation modification of proteins by SVM.
AB  - Attachment of a myristoyl group to NH(2)-terminus of a nascent protein among
      protein post-translational modification (PTM) is called myristoylation. The
      myristate moiety of proteins plays an important role for their biological
      functions, such as regulation of membrane binding (HIV-1 Gag) and enzyme activity
      (AMPK). Several predictors based on protein sequences alone are hitherto
      proposed. However, they produce a great number of false positive and false
      negative predictions; or they cannot be used for general purpose (i.e., taxon
      specific); or threshold values of the decision rule of predictors need to be
      selected with cautiousness. Here, we present novel and taxon-free predictors
      based on protein primary structure. To identify myristoylated proteins
      accurately, we employ a widely used machinelearning algorithm, support vector
      machine (SVM). A series of SVM predictors are developed in the present study
      where various scales representing physicochemical and biological properties of
      amino acids (from the AAindex database) are used for numerical transformation of
      protein sequences. Of the predictors, the top ten achieve accuracies of >98% (the
      average value is 98.34%), and also the area under the ROC curve (AUC) values of
      >0.98. Compared with those of previous studies, the prediction accuracies are
      improved by about 3 to 4%.

PMID- 21738316
TI  - CytReD: A database collecting human cytokinome information.
AB  - The cytokines/related receptors system represents a complex regulatory network
      that is involved in those chronic inflammatory processes which lead to many
      diseases as cancers. We developed a Cytokine Receptor Database (CytReD) to
      collect information on cytokine receptors related to their biological activity,
      gene data, protein structures and diseases in which these and their ligands are
      implicated. This large set of information may be used by researchers as well as
      by physicians or clinicians to identify which cytokines, reported in the
      literature, are important in a given disease and, therefore, useful for purposes
      of diagnosis or prognostic. AVAILABILITY: The database is available for free at
      http://www.cro-m.eu/CytReD/

PMID- 21738317
TI  - Modeling and phylogeny analysis of bread wheat MnSOD.
AB  - Superoxide dismutase (SOD) acts as first line of defense against oxidative and
      genetic stress. Manganese superoxide dismutase (MnSOD), found in mitochondria or
      peroxisomes, contains Mn(III) at the active site. Therefore, it is of interest to
      study MnSOD from bread wheat (a grain crop). However, a structure model is not
      yet solved for bread wheat MnSOD. Hence, we describe the structure model of bread
      wheat MnSOD developed using homology model. The model provides molecular insight
      to metal binding molecular function towards the understanding of oxidative stress
      resistance in plants. The distinction of bread wheat (a monocot) MnSOD from
      dicots is also shown using phylogenetic analysis.

PMID- 21738318
TI  - Construction of efficient and effective transformation vectors for palmitoyl-acyl
      carrier protein thioesterase gene silencing in oil palm.
AB  - Palm oil obtained from E. guineensis Jacq. Tenera is known to have about 44% of
      palmitic acid (C16:0). Palmitoyl-Acyl Carrier Protein Thioesterase (PATE) is one
      of the key enzymes involved in plastidial fatty acid biosynthesis; and it
      determines the level of the C16:0 assimilation in oilseeds. This enzyme's
      activity in oil palm is responsible for high (> 44 % in E. guineensis Jacq.
      Tenera and 25 % in E. oleifera) content of C16:0 in its oil. By post
      transcriptional PATE gene silencing, C16:0 content can be minimized for
      nutritional value improvement of the palm oil. The objective of this study was
      the construction of novel transformation vectors for PATE gene silencing. Six
      different transformation vectors targeted against PATE gene were constructed
      using 619 bp long PATE gene (5' region) fragment (from GenBank AF507115). In one
      set of three transformation vectors, PATE gene fragment was fused with CaMV 35S
      promoter in antisense, intron-spliced inverted repeat (ISIR), and inverted repeat
      (IR) orientations to generate antisense mRNA and hair-pin RNAs (hpRNA). In
      another set of three transformation vectors with same design, CaMV 35S was
      replaced with Oil palm mesocarp tissue-specific promoter (MSP). The expression
      cassette of antisense, ISIR, and IR of PATE gene fragments were constructed in
      primary cloning vector, pHANNIBAL or its derivative/s. Finally, all 6 expression
      cassettes were sub-cloned into pCAMBIA 1301 which contains the Hygromycinr and
      the GUS reporter genes for transformant selection and transformation detection
      respectively. The results of the RE analyses of the constructs and sequence
      analyses of PATE and MSP shows and confirms the orientation, size and locations
      of all the components from constructs. We hypothesize that 4 (pISIRPATE-PC,
      pIRPATE-PC, pMISIRPATE-PC and pMIRPATE-PC) out of 6 transformation vectors
      constructed in this study will be efficient and effective in palmitoyl-ACP
      thioesterase gene silencing in oil palm. ABBREVIATIONS: antiPATE - Antisense
      Palmitoyl-acyl carrier protein thioesterase, BCV - Binary cloning vector, cDNA -
      Complementary deoxyribonucleic acid, hpRNA - hair-pin RNA, ihpRNA - intron
      containing hair-pin RNA, IR - inverted repeat, ISIR - intron-spliced inverted
      repeat, MCS - Multiple cloning site, MSP - Oil palm mesocarp tissue-specific
      promoter, nt - Nucleotide/s, PATE - Palmitoyl-acyl carrier protein thioesterase,
      PCR - Polymerase chain reaction, PCV - Primary cloning vector, pDNA - Plasmid
      deoxyribonucleic acid, PTGS - Post-transcriptional gene silencing, RE -
      Restriction enzyme.

PMID- 21738319
TI  - Binding mode prediction and inhibitor design of anti-influenza virus diketo acids
      targeting metalloenzyme RNA polymerase by molecular docking.
AB  - Influenza is a yearly seasonal threat and major cause of mortality, particularly
      in children and the elderly. Although neuraminidase inhibitors and M2 protein
      blockers are used for medication, drug resistance has gradually emerged. Thus,
      the development of effective anti-influenza drugs targeting different constituent
      proteins of the virus is urgently desired. In this light, we carried out
      molecular docking to predict the binding modes of anti-influenza diketo acid
      inhibitors in the active site of the PAN subunit of the metalloenzyme RNA
      polymerase of influenza virus. The calculations suggested that the dianionic
      forms of the diketo acids should chelate the dinuclear manganese center as
      dinucleating ligands and sequester it. They also indicated that the diketo acid
      derivatives with larger hydrophobic substituents should block a hydrophobic
      cavity in the active site more tightly. These assumptions could adequately
      explain the enzyme inhibition by these compounds. Furthermore, we designed
      potential inhibitors by lead optimization of a diketo acid inhibitor from the
      thermodynamic points of view. Molecular docking results showed that the newly
      designed diketo acid derivatives might inhibit the metalloenzyme RNA polymerase
      more strongly than the lead inhibitor.

PMID- 21738320
TI  - Structure based virtual screening of anticanerous polyphenolic phytocompounds
      against G-protein coupled receptor and identification of potent antagonist
      ligand(s) through molecular docking.
AB  - Design of potential drug-like candidates for cancer is of interest in recent
      years. We used 60 compounds which are known to have the potential to down
      regulate Nuclear Factor kappaB (NFkappaB) for this study. The compounds were
      assessed for Lipinski's RO5 and ADMET properties. Allixin, anethole, capsaicin,
      linearol and syringic acid satisfied both Lipinski's RO5 and ADMET properties.
      These compounds showed strong molecular interaction with receptor GPCR55
      indicating they have ability to block GPCR55. Thus, their role in anticellular
      proliferation and induction of apoptosis is implied.

PMID- 21738321
TI  - Flavonoids lower Alzheimer's Abeta production via an NFkappaB dependent
      mechanism.
AB  - Alzheimer's disease (AD) is characterized by the brain accumulation of Abeta
      peptides and by the presence of neurofibrillary tangles. Abeta is believed to
      play an important role in AD and it has been shown that certain flavonoids can
      affect Abeta production. Recently, it was suggested that the Abeta lowering
      properties of flavonoids are mediated by a direct inhibition the beta-secretase
      (BACE-1) activity, the rate limiting enzyme responsible for the production of
      Abeta peptides. Westernblots and ELISAs were employed to monitor the impact of
      flavonoids on amyloid precursor protein processing and Abeta production. A cell
      free chemoluminescent assay using human recombinant BACE-1 was used to assess the
      effect of flavonoids on BACE-1 activity. The effect of flavonoids on NFkappaB
      activation was determined by using a stable NFkappaB luciferase reporter cell
      line. Molecular docking simulations were performed to predict the binding of
      flavonoids to the BACE-1 catalytic site. Real time quantitative PCR was used to
      determine the effect of flavonoids on BACE-1 transcription. We show in a cell
      free assay that flavonoids are only weak inhibitors of BACE-1 activity. Docking
      simulation studies with different BACE-1 structures also suggest that flavonoids
      are poor BACE-1 inhibitors as they appear to adopt various docking poses in the
      active site pocket and have weak docking scores that differ as a function of the
      BACE-1 structures studied. Moreover, a weak correlation was observed between the
      effect of flavonoids on Abeta production in vitro and their ability to lower BACE
      1 activity suggesting that the Abeta lowering properties of flavonoids in whole
      cells are not mediated via direct inhibition of BACE-1 activity. We found however
      a strong correlation between the inhibition of NFkappaB activation by flavonoids
      and their Abeta lowering properties suggesting that flavonoids inhibit Abeta
      production in whole cells via NFkappaB related mechanisms. As NFkappaB has been
      shown to regulate BACE-1 expression, we show that NFkappaB lowering flavonoids
      inhibit BACE-1 transcription in human neuronal SH-SY5Y cells. Altogether, our
      data suggest that flavonoids inhibit Abeta and sAPPbeta production by regulating
      BACE-1 expression and not by directly inhibiting BACE-1 activity.

PMID- 21738322
TI  - An ANN model for treatment prediction in HBV patients.
AB  - Two types of antiviral treatments, namely, interferon and nucleoside/nucleotide
      analogues are available for hepatitis infections. The selection of drug and dose
      determined using known pharmacokinetics and pharmacodynamics data is important.
      The lack of sufficient information for pharmacokinetics of a drug may not produce
      the desired results. Artificial neural network (ANN) provides a novel model
      independent approach to pharmacokinetics and pharmacodynamics data. ANN model is
      created by supervised learning of 90 patients sample to predict the treatment
      strategy (lamivudine only and Lamivudine + Interferon) on the basis of viral
      load, liver function test, visit number, treatment duration, ethnic area, sex,
      and age. The model was trained with 68 (77.3%) samples and tested with 20 (22.7%)
      samples. The model produced 92% accuracy with 92.8% sensitivity and 83.3%
      specificity.

PMID- 21738323
TI  - The open-access dataset for insilico cardiotoxicity prediction system.
AB  - Drug cardiotoxicity is one of the main reasons of fatal drug related problem
      events and the subsequent withdrawals. Therefore, its early assessment is a
      crucial element of the drug development process. For the drug driven hERG
      inhibition assessment, which is assumed to be the main reason for toxicity, in
      vitro techniques are used. Gold standards are based on the Patch Clamp method
      with the use of various cell models but due to its low throughput, insilico
      models have become more appreciated. To develop a reliable empirical QSAR model,
      wide dataset containing a variety of cases has to be available. In this article,
      a freely available for download, set of data is described. It is based on
      literature peer-reviewed reports and contains hERG inhibition information
      expressed as IC50 value for 263 molecules described in 642 records. All studies
      were done with the use of three cell models (XO, CHO, HEK) and other elements
      describe the electrophysiological settings of the in vitro study. The above
      mentioned set was used for the successful development of the predictive models.

PMID- 21738324
TI  - Characterization of Lovastatin biosynthetic cluster proteins in Aspergillus
      terreus strain ATCC 20542.
AB  - Aspergillus terreus is a filamentous ascomycota, which is prominent for its
      production of lovastatin, an antihypercholesterolemic drug. The commercial
      importance of lovastatin with annual sales of billions of dollars made us to
      focus on lovastatin biosynthetic cluster proteins. The analysis of these
      lovastatin biosynthetic cluster proteins with different perspectives such as
      physicochemical property, structure based analysis and functional studies were
      done to find out the role and function of every protein involved in the
      lovastatin biosynthesis pathway. Several computational tools are used to predict
      the physicochemical properties, secondary structural features, topology,
      patterns, domains and cellular location. There are 8 unidentified proteins in
      lovastatin biosynthetic cluster, in which 6 proteins have homologous partners,
      and annotation transfer is done based on the closely related homologous genes,
      and their structures are also modeled. The two other proteins that do not have
      homologous partners are predicted as PQ loop repeat protein that may be involved
      in glycosylation machinery and as thiolase-acyl activity by the integrated
      functional analysis approach.

PMID- 21738325
TI  - Population coverage analysis of T-Cell epitopes of Neisseria meningitidis
      serogroup B from Iron acquisition proteins for vaccine design.
AB  - Although the concept of Reverse Vaccinology was first pioneered for sepsis and
      meningococcal meningitidis causing bacterium, Neisseria meningitides, no broadly
      effective vaccine against serogroup B meningococcal disease is yet available. In
      the present investigation, HLA distribution analysis was undertaken to select
      three most promiscuous T-cell epitopes out of ten computationally validated
      epitopes of Iron acquisition proteins from Neisseria MC58 by using the population
      coverage tool of Immune Epitope Database (IEDB). These epitopes have been
      determined on the basis of their binding ability with maximum number of HLA
      alleles along with highest population coverage rate values for all the
      geographical areas studied. The comparative population coverage analysis of
      moderately immunogenic and high immunogenic peptides suggests that the former may
      activate T-cell response in a fairly large proportion of people in most
      geographical areas, thus indicating their potential for development of epitope
      based vaccine.

PMID- 21738326
TI  - Computer aided screening of inhibitors to 5-alpha reductase type 2 for prostate
      cancer.
AB  - Traditionally, drugs are discovered by testing compounds synthesized in time
      consuming multi-step processes against a battery of invivo biological screens.
      Promising compounds are then further studied in development, where their
      pharmacokinetic properties, metabolism and potential toxicity were investigated.
      Here, we present a study on herbal lead compounds and their potential binding
      affinity to the effectors molecules of major disease like Prostate Cancer.
      Clinical studies demonstrate a positive correlation between the extent of 5-alpha
      reductase type 2 (isoform 2) and malignant progression of precancerous lesions in
      prostate. Therefore, identification of effective, well-tolerated 5-alpha
      reductase inhibitors represents a rational chemo preventive strategy. This study
      has investigated the effects of naturally occurring nonprotein compounds
      berberine and monocaffeyltartaric acid that inhibits 5-alpha reductase type 2.
      Our results reveal that these compounds use less energy to bind to 5-alpha
      reductase and inhibit its activity. Their high ligand binding affinity to 5-alpha
      reductase introduces the prospect for their use in chemopreventive applications.
      In addition, they are freely available natural compounds that can be safely used
      to prevent prostate cancer.

PMID- 21738327
TI  - Molecular basis of antigenic drift in Influenza A/H3N2 strains (1968-2007) in the
      light of antigenantibody interactions.
AB  - The emergence of new strains of Influenza virus have caused several pandemics
      over the last hundred years with the latest being the H1N1 Swine flu pandemic of
      2009. The Hemagglutinin (HA) protein of the Influenza virus is the primary target
      of human immune system and is responsible for generation of protective antibodies
      in humans. Mutations in this protein results in change in antigenic regions
      (antigenic drift) which consequently leads to loss of immunity in hosts even in
      vaccinated population (herd immunity). This necessitates periodic changes in the
      Influenza vaccine composition. In this paper, we investigate the molecular basis
      of the reported loss of herd immunity in vaccinated population (vaccine
      component: Influenza A/X-31/1968 (H3N2)) which resulted in the outbreak due to
      strain Influenza A/Port Chalmers/1/1973 (H3N2). Also, the effects of antigenic
      drift in HA protein (H3N2 vaccine strains 1968-2007) on the 3D structures as well
      as interactions with BH151, a 1968 antibody, has been studied. Rigid body
      molecular docking protocol has been used to study the antigen-antibody
      interactions. We believe that the present study will help in better understanding
      of host-pathogen interactions at the molecular level.

PMID- 21738328
TI  - Immunoinformatics prediction of linear epitopes from Taenia solium TSOL18.
AB  - Cysticercosis is a public health problem in several developing countries. The
      oncosphere protein TSOL18 is the most immunogenic and protective antigen ever
      reported against porcine cysticercosis, although no specific epitope has been
      identified to account for these properties. Recent evidence suggests that
      protection might be associated with conformational epitopes. Linear epitopes from
      TSOL18 were computationally predicted and evaluated for immunogenicity and
      protection against porcine cysticercosis. A synthetic peptide was designed based
      on predicted linear B cell and T cell epitopes that are exposed on the surface of
      the theoretically modeled structure of TSOL18. Three surface epitopes from TSOL18
      were predicted as immunogenic. A peptide comprising a linear arrangement of these
      epitopes was chemically synthesized. The capacity of the synthetic peptide to
      protect pigs against an oral challenge with Taenia solium proglottids was tested
      in a vaccine trial. The synthetic peptide was able to produce IgG antibodies in
      pigs and was associated to a reduction of the number of cysts, although was not
      able to provide complete protection, defined as the complete absence of cysts in
      necropsy. This study demonstrated that B cell and T cell predicted epitopes from
      TSOL18 were not able to completely protect pigs against an oral challenge with
      Taenia solium proglottids. Therefore, other linear epitopes or eventually
      conformational epitopes may be responsible for the protection conferred by
      TSOL18.

PMID- 21738329
TI  - Physicochemical characterization and functional site analysis of lactoferrin gene
      of Vechur cow.
AB  - The Bos indicus Vechur breed cow milk is known for its medicinal value and the
      breed is listed under the category of critically maintained breeds by the Food
      and Agriculture Organization. The lactoferrin protein in milk is known for its
      nutritional value. Gene polymorphisms have been reported for Bovine lactoferrin.
      Mutations in the evolutionarily conserved sites tend to impair protein function
      and are related with the physicochemical difference between the known variants
      with 11 SNPs within the wild type. Structural differences are located due to
      these SNPs that may lead to functional variations. The structural variation is
      seen primarily in the first 48 residues at 5' end in all the samples modelled.
      Out of 11 SNPs 5 amino acid variations fall under alpha helix and beta sheet
      region, this might be of functional significance. This result may provide
      evidence that the SNPs detected in lactoferrin gene might have potential effects
      on milk composition. Our result demonstrates one major domain that could be a
      common binding pocket to all the samples, and important as an active site common
      to all the breeds that could be utilized for effective drug designing. Moreover,
      at some SNP positions in Vechur breed, antimicrobial peptides were located
      indicating importance of those residues for enhanced antimicrobial activity in
      lactoferrin of Vechur breed. Second binding pocket found in N- lobe region with
      the three required residues aspartic acid, histidine and tyrosine for iron
      binding, was considered as major binding site.

PMID- 21738330
TI  - Robust consensus clustering for identification of expressed genes linked to
      malignancy of human colorectal carcinoma.
AB  - Previous studies have been conducted in gene expression profiling to identify
      groups of genes that characterize the colorectal carcinoma disease. Despite the
      success of previous attempts to identify groups of genes in the progression of
      the colorectal carcinoma disease, their methods either require subjective
      interpretation of the number of clusters, or lack stability during different runs
      of the algorithms. All of which limits the usefulness of these methods. In this
      study, we propose an enhanced algorithm that provides stability and robustness in
      identifying differentially expressed genes in an expression profile analysis. Our
      proposed algorithm uses multiple clustering algorithms under the consensus
      clustering framework. The results of the experiment show that the robustness of
      our method provides a consistent structure of clusters, similar to the structure
      found in the previous study. Furthermore, our algorithm outperforms any single
      clustering algorithms in terms of the cluster quality score.

PMID- 21738331
TI  - Analysis of sequence diversity among IS6110 sequence of Mycobacterium
      tuberculosis: possible implications for PCR based detection.
AB  - The IS6110 belongs to the family of insertion sequences (IS) of the IS3 category.
      This insertion sequence was reported to be specific for Mycobacterium
      tuberculosis complex and hence is extensively exploited for laboratory detection
      of the agent of tuberculosis and for epidemiological investigations based on
      polymerase chain reaction. IS6110 is 1361-bp long and within this sequence
      different regions have been utilized as targets in the identification of M.
      tuberculosis by PCR. However, the results are not always consistent, specific and
      sensitive. In recent years, a few clinical investigations raised concerns over
      IS6110 specificity and sensitivity in the diagnosis of tuberculosis due to false
      positive (homology with other target DNA besides M. tuberculosis) or false
      negative (due to absence of copies of IS6110) results with IS6110 specific
      primers. To unravel the variations in IS6110 sequences, an insilico analysis of
      IS6110 sequence of different strains of M. tuberculosis was carried out. Our
      results of comparative analysis of IS6110 insertion sequences of M. tuberculosis
      complex suggests that, IS6110 insertion sequences harbored variations in its
      sequence, which is evident from the phylogenetic analysis. Importantly, IS6110
      sequence has divergence within the copies of same strain and formed different
      clusters. A list of IS6110 specific primers used in various clinical
      investigation of tuberculosis was obtained from the literature and their
      performance scrutinized. Our study emphasizes the need to develop PCR assays
      (multiplex format) targeting more than one region of the genome of M.
      tuberculosis.

PMID- 21738332
TI  - MAP Kinase analyser: A tool for plant kinase and substrate analysis.
AB  - MAPK (Mitogen Activated Protein Kinase) is a Ser/Thr kinase, which plays a
      crucial role in plant growth and development, transferring the extra cellular
      stimuli into intracellular response etc. Manual identification of these MAPK in
      the plant genome is tedious and time taking process. There are number of online
      servers which predict the P-site (phosphorylation site), find the motifs and
      domain but there is no specific tool which can identify all them together. In
      order to identify the P-Site, phosphorylation site consensus sequences and domain
      of the MAPK in plant genome, we developed a tool, MAP Kinase analyzer. MAP kinase
      analyzer take protein sequence as input in the fasta format and the output of
      tool includes: 1) The prediction of the phosphorylation site viz., Serine (S),
      Threonine (T), and Tyrosine (Y), Contex, Position, Score and phosphorylating
      kinase as well as the graphical output; 2) Phosphorylation site consensus
      sequence pattern for different kinases and 3) Domain information about the
      MAPK's. The MAP kinase analyser tool and supplementary files can be downloaded
      from http://www.bioinfogbpuat/mapk_OWN_1/.

PMID- 21738333
TI  - OntoVisT: A general purpose Ontological Visualization Tool.
AB  - Ontologies have emerged as a fast growing research topic in the area of semantic
      web during last decade. Currently there are 204 ontologies that are available
      through OBO Foundry and BioPortal. Several excellent tools for navigating the
      ontological structure are available, however most of them are dedicated to a
      specific annotation data or integrated with specific analysis applications, and
      do not offer flexibility in terms of general-purpose usage for ontology
      exploration. We developed OntoVisT, a web based ontological visualization tool.
      This application is designed for interactive visualization of any ontological
      hierarchy for a specific node of interest, up to the chosen level of children
      and/or ancestor. It takes any ontology file in OBO format as input and generates
      output as DAG hierarchical graph for the chosen query. To enhance the navigation
      capabilities of complex networks, we have embedded several features such as
      search criteria, zoom in/out, center focus, nearest neighbor highlights and mouse
      hover events. The application has been tested on all 72 data sets available in
      OBO format through OBO foundry. The results for few of them can be accessed
      through OntoVisT-Gallery. AVAILABILITY: The database is available for free at
      http://ccbb.jnu.ac.in/OntoVisT.html.

PMID- 21738334
TI  - Capturing the regenerative potential of periodontal ligament fibroblasts.

PMID- 21738335
TI  - Gene expression profile during chondrogenesis in human bone marrow derived
      mesenchymal stem cells using a cDNA microarray.
AB  - Mesenchymal stem cells (MSCs) have the capacity to proliferate and differentiate
      into multiple connective tissue lineages, which include cartilage, bone, and fat.
      Cartilage differentiation and chondrocyte maturation are required for normal
      skeletal development, but the intracellular pathways regulating this process
      remain largely unclear. This study was designed to identify novel genes that
      might help clarify the molecular mechanisms of chondrogenesis. Chondrogenesis was
      induced by culturing human bone marrow (BM) derived MSCs in micromass pellets in
      the presence of defined medium for 3, 7, 14 or 21 days. Several genes regulated
      during chondrogenesis were then identified by reverse transcriptase-polymerase
      chain reaction (RT-PCR). Using an ABI microarray system, we determined the
      differential gene expression profiles of differentiated chondrocytes and BM-MSCs.
      Normalization of this data resulted in the identification of 1,486 differentially
      expressed genes. To verify gene expression profiles determined by microarray
      analysis, the expression levels of 10 genes with high fold changes were confirmed
      by RT-PCR. Gene expression patterns of 9 genes (Hrad6B, annexinA2, BMP-7,
      contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin
      IV, serotonin receptor-7, Axl) in RT-PCR were similar to the microarray gene
      expression patterns. These findings provide novel information concerning genes
      involved in the chondrogenesis of human BM-MSCs.

PMID- 21738336
TI  - Risk factors for recurrence of Clostridium difficile infection: effect of
      vancomycin-resistant enterococci colonization.
AB  - Recurrent Clostridium difficile infection (CDI) is one of the most difficult
      problems in healthcare infection control. We evaluated the risk factors
      associated with recurrence in patients with CDI. A retrospective cohort study of
      84 patients with CDI from December 2008 through October 2010 was performed at
      Pusan National University Yangsan Hospital. Recurrence occurred in 13.1% (11/84)
      of the cases and in-hospital mortality rate was 7.1% (6/84). Stool colonization
      with vancomycin-resistant enterococci (VRE) (P = 0.006), exposure to more than 3
      antibiotics (P = 0.009), low hemoglobin levels (P = 0.025) and continued use of
      previous antibiotics (P = 0.05) were found to be more frequent in the recurrent
      group. Multivariate analysis indicated that, stool VRE colonization was
      independently associated with CDI recurrence (odds ratio, 14.519; 95% confidence
      interval, 1.157-182.229; P = 0.038). This result suggests that stool VRE
      colonization is a significant risk factor for CDI recurrence.

PMID- 21738337
TI  - Usefulness of quantitative endotracheal aspirate cultures in intensive care unit
      patients with suspected pneumonia.
AB  - It is difficult to differentiate pathogens responsible for pneumonia or
      colonization in patients with an endotracheal tube or in patients that have
      undergone tracheostomy. We evaluated the clinical usefulness of quantitative
      endotracheal aspirates cultures and sought to determine the result threshold
      level for positivity. The authors performed this retrospective cohort study
      between December 1, 2004 and January 31, 2006. Forty-five suspected pneumonia
      patients admitted to an intensive care unit (ICU) with quantitative
      bronchoalveolar lavage (BAL) and endotracheal aspirate (EA) culture results were
      enrolled. Using a threshold of 10(5) cfu/mL, 10 of the 45 (22.2%) quantitative EA
      cultures were positive, as compared with 7 (15.6%) BAL cultures. When BAL culture
      findings were used as the reference, the sensitivity and specificity of
      quantitative EA cultures were 85.7% and 89.5%, respectively, at a threshold of
      10(5) cfu/mL, and 85.7% and 94.7%, respectively, at a threshold of 10(6) cfu/mL.
      Of the 10 EA culture positive patients, 2 patients with a result of -10(5) cfu/mL
      were BAL culture negative. The quantitative EA culture is a useful non-invasive
      tool for the diagnosis of pneumonia pathogens. It is suggested that a threshold
      level of 10(6) cfu/mL is appropriate.

PMID- 21738338
TI  - FCepsilonRI gene promoter polymorphisms and total IgE levels in susceptibility to
      atopic dermatitis in Korea.
AB  - IgE-dependent activation of mast cells and basophils through the high-affinity
      IgE receptor (FcepsilonRI) is involved in the pathogenesis of allergen-induced
      immune responsiveness in atopic diseases like atopic dermatitis (AD). We sought
      to determine FcepsilonRI gene polymorphisms are associated with AD in Korean
      patients, and analyzed the relevance of FcepsilonRI gene polymorphisms and serum
      IgE levels. We conducted a case-control association analysis (175 patients and 56
      controls) of Korean subjects. Genotyping was performed using the TaqMan
      fluorogenic 5' nuclease assay, and serum levels of IgE were measured using a
      fluorescence enzyme immunoassay. We found that there were no significant
      relationships between FcepsilonRI and AD, although there were trends towards an
      association between the 66T>C (rs2251746) polymorphism and total serum IgE levels
      in the Korean AD patients. In conclusion, while the 66T>C (rs2251746) of the
      FcepsilonRIalpha polymorphism may be linked to AD and higher serum IgE levels,
      polymorphisms in the FcepsilonRIbeta gene did not confer susceptibility to AD in
      our patient sample.

PMID- 21738339
TI  - Detecting the recurrence of gastric cancer after curative resection: comparison
      of FDG PET/CT and contrast-enhanced abdominal CT.
AB  - The purpose of this study was to evaluate the value of fluorodeoxyglucose
      positron emission tomography/computed tomography (FDG PET/CT) for detecting the
      recurrence of gastric cancer. We performed a retrospective review of 139
      consecutive patients who underwent PET/CT and contrast-enhanced abdominal CT
      (CECT) for surveillance of gastric cancer after curative resection. Recurrence of
      gastric cancer was validated by histopathologic examination for local recurrence
      or serial imaging study follow-up with at least 1 yr interval for recurrence of
      distant metastasis form. Twenty-eight patients (20.1%) were confirmed as
      recurrence. On the patient based analysis, there was no statistically significant
      difference in the sensitivity, specificity and accuracy of PET/CT (53.6%, 84.7%,
      and 78.4%, respectively) and those of CECT (64.3%, 86.5%, and 82.0%,
      respectively) for detecting tumor recurrence except in detection of peritoneal
      carcinomatosis. Among 36 recurrent lesions, 8 lesions (22.2%) were detected only
      on PET/CT, and 10 lesions (27.8%) only on CECT. PET/CT had detected secondary
      malignancy in 8 patients. PET/CT is as accurate as CECT in detection of gastric
      cancer recurrence after curative resection, excepting detection of peritoneal
      carcinomatosis. Moreover, additional PET/CT on CECT could improve detection rate
      of tumor recurrence and provide other critical information such as unexpected
      secondary malignancy.

PMID- 21738340
TI  - Clinical implications of immunohistochemically demonstrated lymph node
      micrometastasis in resectable pancreatic cancer.
AB  - The purpose of this study was to determine the clinical significance of nodal
      micrometastasis detected by immunohistochemistry in patients that had undergone
      curative surgery for pancreatic cancer. Between 2005 and 2006, a total of 208
      lymph nodes from 48 consecutive patients with pancreatic cancer that had
      undergone curative resection were immunostained with monoclonal antibody against
      pan-ck and CK-19. Micrometastasis was defined as metastasis missed by a routine
      H&E examination but detected during an immunohistochemical evaluation. Relations
      between immunohistochemical results and clinical and pathologic features and
      patient survival were examined. Nodal micrometastases were detected in 5 (29.4%)
      patients of 17 pN0 patients. Nodal micrometastasis was found to be related to
      tumor relapse (P = 0.043). Twelve patients without overt nodal metastasis and
      micrometastasis had better prognosis than 5 patients with only nodal
      micrometastasis (median survival; 35.9 vs 8.6 months, P < 0.001). The Cox
      proportional hazard model identified nodal micrometastasis as significant
      prognostic factors. Although the number of patients with micrometastasis was so
      small and further study would be needed, our study suggests that the lymph node
      micrometastasis could be the predictor of worse survival and might indicate
      aggressive tumor biology among patients undergoing curative resection for
      pancreas cancer.

PMID- 21738341
TI  - Spectra of chromosomal aberrations in 325 leukemia patients and implications for
      the development of new molecular detection systems.
AB  - This study investigated the spectrum of chromosomal abnormalities in 325 leukemia
      patients and developed optimal profiles of leukemic fusion genes for multiplex RT
      PCR. We prospectively analyzed blood and bone marrow specimens of patients with
      acute leukemia. Twenty types of chromosomal abnormalities were detected in 42%
      from all patients by commercially available multiplex RT-PCR for detecting 28
      fusion genes and in 35% by cytogenetic analysis including FISH analysis. The most
      common cytogenetic aberrations in acute myeloid leukemia patients was PML/PARA,
      followed by AML1/MGT8 and MLL1, and in acute lymphoid leukemia patients was
      BCR/ABL, followed by TEL/AML1 and MLL1 gene rearrangement. Among the negative
      results for multiplex RT-PCR, clinically significant t(3;3)(q21;q26.2),
      t(8;14)(q24;q32) and i(17)(q10) were detected by conventional cytogenetics. The
      spectrum and frequency of chromosomal abnormalities in our leukemia patients are
      differed from previous studies, and may offer optimal profiles of leukemic fusion
      genes for the development of new molecular detection systems.

PMID- 21738342
TI  - Antiproliferation and redifferentiation in thyroid cancer cell lines by
      polyphenol phytochemicals.
AB  - Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and
      refractory to radioiodine and thyroid stimulating hormone (TSH) suppression
      therapy. Redifferentiating agents have been shown to inhibit tumor growth and
      improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in
      fruits and vegetables have been reported to inhibit cancer initiation, promotion,
      progression and induce redifferentiation in selected types. In this study we
      examined PPs induce redifferentiation in thyroid cancer cell lines. We
      investigated the effects of genistein, resveratrol, quercetin, kaempferol, and
      resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid
      cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition
      in response to genistein, resveratrol, quercetin. We further demonstrated that
      genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol
      decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all
      cell lines. We observed increased expression of differentiation marker NIS in FTC
      133 cells in response to genistein, and resveratrol but no change in NPA, FRO,
      ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These
      findings suggest that PPs may provide a useful therapeutic intervention in
      thyroid cancer redifferentiation therapy.

PMID- 21738343
TI  - Differential relationship between metabolic syndrome score and severity of
      coronary atherosclerosis as assessed by angiography in a non-diabetic and
      diabetic Korean population.
AB  - Whether the metabolic syndrome (MetS) has prognostic value for coronary artery
      disease (CAD) beyond its individual components is controversial. We compared the
      relationship between the number of MetS components and CAD severity as assessed
      by angiography in non-diabetic and diabetic subjects. We consecutively enrolled
      527 patients who underwent their first coronary angiography. Patients were
      divided into four groups according to the number of MetS components: 0/1, 2, 3,
      and 4/5. A coronary atherosclerosis score was used to quantify the extent of
      atherosclerotic involvement. The relationship between the MetS score and
      angiographic CAD severity or clinical presentation was compared between non
      diabetic and diabetic subjects. Individuals with the MetS (n = 327) had a higher
      prevalence of CAD (60% vs 32%, P < 0.001), multi-vessel disease (34% vs 16%, P <
      0.001), and acute coronary syndromes (49% vs 26%, P < 0.001) than those without
      the MetS. In the non-diabetic group, atherosclerosis score increased with the
      MetS score (1.0 +/- 2.1, 2.0 +/- 2.9, 2.8 +/- 2.9, and 3.6 +/- 3.9, P < 0.001)
      whereas there was no significant difference in the diabetic group (0.5 +/- 1.0,
      5.2 +/- 4.7, 4.2 +/- 2.9, and 4.4 +/- 3.5, P = 0.102). The MetS score is related
      to CAD severity in non-diabetic patients but the association between the MetS
      score and angiographic CAD severity may be obscured in the presence of diabetes.

PMID- 21738344
TI  - Gender differences in diagnostic values of visceral fat area and waist
      circumference for predicting metabolic syndrome in Koreans.
AB  - Abdominal fat accumulation is known to be strongly implicated in development of
      metabolic syndrome (MetS). We examined diagnostic values of obesity-related
      parameters in 95 men and 185 women, and we determined optimal cutoff values of
      visceral fat area (VFA) and waist circumference (WC) for predicting the presence
      of multiple non-adipose components of MetS. Receiver operating characteristic
      (ROC) curve analysis revealed that VFA was the best indicator of MetS. WC and VFA
      exhibited similar diagnostic values for men and postmenopausal women, whereas WC
      was inferior to VFA for premenopausal women (area under ROC curve of VFA and WC
      was 0.76 and 0.52, respectively; P < 0.001). Optimal cutoff points of VFA and WC
      for predicting MetS were 136 cm(2) and 89 cm in men and 95 cm(2) and 82 cm in
      women, respectively. Subjects with VFA and WC above these cutoff values exhibited
      increased insulin resistance and increased carotid intima-media thickness. In
      conclusion, WC has a diagnostic value similar to VFA for predicting MetS in men
      and postmenopausal women, but not in premenopausal women. Further studies are
      necessary to develop a simple clinical parameter that reflects visceral fat in
      premenopausal women.

PMID- 21738345
TI  - Association of cortisol and the metabolic syndrome in Korean men and women.
AB  - Obesity and the metabolic syndrome are closely related and have become
      increasingly prevalent in Korea. The cardiovascular disease (CVD) risk factors
      comprising the metabolic syndrome have previously been associated with increased
      hypothalamic-pituitary-adrenal axis (HPAA) activity, but the associations have
      not been extensively examined in non-Caucasian populations. The aim of the
      present study was to investigate the relationships between cortisol, adiposity
      and the metabolic syndrome in a Korean population. A total of 1,881 adults
      participated in the study between January 2001 and February 2008.
      Sociodemographic data were assessed by questionnaires. Body composition, clinic
      blood pressures as well as metabolic variables including glucose, insulin, and
      lipid profile were assessed and analyzed in relation to cortisol levels. Mean age
      of the participants was 58.7 +/- 10.8 yr. Higher levels of cortisol was
      associated with elevated blood pressure, fasting glucose and total cholesterol in
      men, and between cortisol and systolic blood pressure, fasting glucose and total
      cholesterol in women. There was an increased risk for the metabolic syndrome
      associated with higher cortisol levels in both men (P < 0.001) and women (P =
      0.040) adjusting for age and body mass index. Higher cortisol levels are
      associated with several CVD risk factors and the metabolic syndrome, independent
      of overall of adiposity level, in Korean men and women.

PMID- 21738346
TI  - CD44 disruption attenuates murine hepatic ischemia/reperfusion injury.
AB  - Neutrophil adhesion and migration are critical in hepatic ischemia/reperfusion
      (I/R) injury. Despite very strong preclinical data, recent clinical trials failed
      to show a protective effect of anti-adhesion therapy in reperfusion injury.
      Therefore, the aim of this study was to assess the role of CD44 in neutrophil
      infiltration and liver injury from hepatic I/R. In this study, using a partial
      hepatic ischemic model in vivo, we determined the potential role of CD44 in
      neutrophil infiltration and liver injury from I/R. Reperfusion caused significant
      hepatocellular injury as it was determined by plasma ALT levels and liver
      histopathology. The injury was associated with a marked neutrophil recruitment
      and CD44 expression into the ischemic livers. Administration of anti-CD44
      antibody to mice reduced the infiltration of neutrophil into the ischemic tissue,
      associated with liver function preservation. These results support crucial roles
      of CD44 in neutrophil recruitment and infiltration leading to liver damage in
      hepatic I/R injury. Moreover, they provide the rationale for targeting to CD44 as
      a potential therapeutic approach in liver I/R injury.

PMID- 21738347
TI  - Serum kisspeptin levels in Korean girls with central precocious puberty.
AB  - Central precocious puberty (CPP) is caused by premature activation of
      hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin and G
      protein coupled receptor-54 system is the essential gatekeeper of the
      reproductive system, playing a key role in the activation of the gonadotropic
      axis at puberty. We aimed to determine whether serum kisspeptin may function as a
      marker for CPP by investigating serum kisspeptin levels in Korean girls with CPP
      and their prepubertal controls. Serum kisspeptin levels of Korean girls with CPP
      (n = 30) and age-matched healthy prepubertal controls (n = 30) were measured with
      a competitive enzyme immunoassay. Serum kisspeptin levels were significantly
      higher in CPP group than in control group (4.61 +/- 1.78 vs 2.15 +/- 1.52 pM/L, P
      < 0.001). Serum kisspeptin was positively correlated with peak luteinizing
      hormone (LH), peak/basal LH ratio and peak LH/follicular-stimulating hormone
      (FSH) ratio during GnRH stimulation test. CPP is supposed to be triggered by
      premature increase of kisspeptin. Serum kisspeptin may be used as a marker of
      CPP. Further studies on KISS1 gene polymorphisms leading to higher risk of
      premature increase of kisspeptin and upstream regulator of kisspeptin are also
      needed.

PMID- 21738348
TI  - Clinical features of abdominal actinomycosis: a 15-year experience of a single
      institute.
AB  - This study was designed to evaluate the clinical features of abdominal
      actinomycosis and to assess its therapeutic outcome. We reviewed patients with
      abdominal actinomycosis in Seoul St. Mary hospital, between January 1994 and
      January 2010. Twenty-three patients (5 male and 18 female, mean age, 47.8 yr;
      range, 6-75 yr), with abdominal actinomycosis were included. Emergency surgery
      was performed in 50% due to symptoms of peritonitis. The common presentation on
      preoperative computerized tomography was a mass with abscess, mimicking
      malignancy. The mean tumor size was 7.0 cm (range, 2.5-10.5). In all patients,
      actinomycotic masses were surgically removed. Mean duration of hospital stay was
      17.8 days (range, 5-49). Long term oral antibiotic treatment (mean 4.2 months;
      range, 0.5-7.0 months) were administered to all patients. All patients were free
      of recurrence after a median follow up of 30.0 months (mean 35.5 +/- 14.8 months,
      range, 10.0-70.0 months); recurrence was not seen in any patient. In conclusion,
      abdominal actinomycosis should be included as a differential diagnosis when an
      unusual abdominal mass or abscess presents on abdominal CT. Assertive removal of
      necrotic tissue with surgical drainage and long term antibiotic treatment provide
      a good prognosis in patients with actinomycosis.

PMID- 21738349
TI  - Interleukin-17 in various ocular surface inflammatory diseases.
AB  - Recently, the association of Th-17 cells or IL-17 with ocular inflammatory
      diseases such as uveitis, scleritis and dry eye syndrome was discovered. We
      assessed whether interleukin (IL)-17 was present in the tears of various ocular
      surface inflammatory diseases and the tear IL-17 concentrations were clinically
      correlated with various ocular surface inflammatory diseases. We measured
      concentrations of IL-17 in tears of normal subjects (n = 28) and patients (n =
      141) with meibomian gland dysfunction (MGD), dry eye syndrome (DES), Sjogren
      syndrome (SS), Stevens-Johnson syndrome (SJS), graft-versus-host disease (GVHD),
      filamentary keratitis, and autoimmune keratitis associated with rheumatoid
      arthritis or systemic lupus erythematosus. Clinical epitheliopathy scores were
      based on the surface area of corneal and conjunctival fluorescein staining. The
      mean concentrations of IL-17 in tears of patients with filamentary keratitis,
      GVHD, autoimmune keratitis, SS, DES, MGD, SJS were significantly higher in order
      than that in normal subjects. Tear IL-17 concentration was significantly
      correlated with clinical epitheilopathy scores in the patients with systemic
      inflammatory disease, while tear IL-17 was not correlated with clinical severity
      of the cornea and conjunctiva in the dry eye patients without any systemic
      inflammatory disease. Tear IL-17 is likely to correlate clinically with corneal
      disease severity only in the patients with systemic inflammatory disease.

PMID- 21738350
TI  - Use of nafamostat mesilate as an anticoagulant during extracorporeal membrane
      oxygenation.
AB  - Although the incidence of bleeding complications during extracorporeal membrane
      oxygenator (ECMO) support has decreased in various trials, bleeding is still the
      most fatal complication. We investigated the ideal dosage and efficacy of
      nafamostat mesilate for use with ECMO in patients with acute cardiac or
      respiratory failure. We assessed 73 consecutive patients who received ECMO due to
      acute cardiac or respiratory failure between January 2006 and December 2009. To
      evaluate the efficacy of nafamostat mesilate, we divided the patients into 2
      groups according to the anticoagulants used during ECMO support. All patients of
      nafamostat mesilate group were male with a mean age of 49.2 yr. Six, 3, 5, and 3
      patients were diagnosed with acute myocardial infarction, cardiac arrest, septic
      shock, and acute respiratory distress syndrome, respectively. The mean dosage of
      nafamostat mesilate was 0.64 mg/kg/hr, and the mean duration of ECMO was 270.7
      hr. The daily volume of transfused packed red blood cells, fresh frozen plasma,
      and cryoprecipitate and the number of complications related to hemorrhage and
      thrombosis was lower in the nafamostat mesilate group than in the heparin group.
      Nafamostat mesilate should be considered as an alternative anticoagulant to
      heparin to reduce bleeding complications during ECMO.

PMID- 21738351
TI  - Identification of a novel mutation in the ATP7A gene in a Korean patient with
      Menkes disease.
AB  - Menkes disease is an infantile-onset X-linked recessive neurodegenerative
      disorder caused by diverse mutations in a copper-transport gene, ATP7A. Affected
      patients are characterized by progressive hypotonia, seizures, failure to thrive
      and death in early childhood. Here, we report a case of Menkes disease presented
      by intractable seizures and infantile spasms. A 3-month-old male infant had
      visited our pediatric clinic for lethargy, floppy muscle tone, poor oral intake
      and partial seizures. His hair was kinky, brown colored and fragile. Partial
      seizures became more frequent, generalized and intractable to antiseizure
      medications. An EEG showed frequent posteriorly dominant generalized spikes that
      were consistent with a generalized seizure. From a genetic analysis, a c.2743C>T
      (p.Gln915X) mutation was detected and diagnosed as Menkes disease. The mutation
      is a novel one that has not been previously reported as a cause of Menkes
      disease.

PMID- 21738352
TI  - Pancreatic endocrine tumors: a report on a patient treated with sorafenib.
AB  - A 31-yr-old man with abdominal pain was diagnosed with a pancreatic endocrine
      tumor and multiple hepatic metastases. Despite optimal treatment with interferon
      alpha, a somatostatin analog, local therapy with high-intensity focused
      ultrasound ablation for multiple hepatic metastases, and multiple lines of
      chemotherapy with etoposide/cisplatin combination chemotherapy and gemcitabine
      monotherapy, the tumor progressed. As few chemotherapeutic options were available
      for him, sorafenib (800 mg/day, daily) was administered as a salvage regimen.
      Sorafenib was continued despite two episodes of grade 3 skin toxicity; it delayed
      tumor progression compared to the previous immunotherapy and chemotherapy. Serial
      computed tomography scans showed that the primary and metastatic tumors were
      stable. Thirteen months after beginning targeted therapy, and up to the time of
      this report, the patient is well without disease progression. We suggest that
      sorafenib is effective against pancreatic endocrine tumors.

PMID- 21738353
TI  - Long QT syndrome and torsade de pointes associated with Takotsubo cardiomyopathy.
AB  - Prolongation of QTc interval associated with Takotsubo cardiomyopathy (TC) has
      previously been reported in published case series. We report an unusual case of a
      patient who presented with TC associated with long-QT syndrome and developed
      cardiac arrest secondary to torsade de pointes. Since QT prolongation and
      bradycardia persisted after the resolution of TC, the patient received permanent
      pacemaker. Since then additional event did not occur. QT prolongation and
      bradycardia could be persistent even after recovery of TC, and permanent
      pacemaker insertion may be a treatment option of long QT syndrome related with
      TC.

PMID- 21738354
TI  - A case of atypical skull base osteomyelitis with septic pulmonary embolism.
AB  - Skull base osteomyelitis (SBO) is difficult to diagnose when a patient presents
      with multiple cranial nerve palsies but no obvious infectious focus. There is no
      report about SBO with septic pulmonary embolism. A 51-yr-old man presented to our
      hospital with headache, hoarseness, dysphagia, frequent choking, fever, cough,
      and sputum production. He was diagnosed of having masked mastoiditis complicated
      by SBO with multiple cranial nerve palsies, sigmoid sinus thrombosis, and septic
      pulmonary embolism. We successfully treated him with antibiotics and
      anticoagulants alone, with no surgical intervention. His neurologic deficits were
      completely recovered. Decrease of pulmonary nodules and thrombus in the sinus was
      evident on the follow-up imaging one month later. In selected cases of
      intracranial complications of SBO and septic pulmonary embolism, secondary to
      mastoiditis with early response to antibiotic therapy, conservative treatment may
      be considered and surgical intervention may be withheld.

PMID- 21738355
TI  - A case of Fabry's disease with congenital agammaglobulinemia.
AB  - Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities
      in the alpha-galactosidase A (GLA) gene, which leads to a GLA deficiency and to
      the intracellular deposition of globotriaosylceramide (Gb3) within vascular
      endothelium and other tissues. It manifests as progressive multiple organ
      dysfunctions caused by the deposition of Gb3. On the other hand, congenital
      agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase
      (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes
      recurrent pyogenic infections. In former reports, the distance between the loci
      in the Xq22 region of the human X chromosome was found to be about 69 kilobases.
      A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed
      typical clinical and laboratory and histopathological findings of Fabry's
      disease. The genetic basis of this combination of the two syndromes was studied
      in this patient. Here, we report a case of Fabry's disease with congenital
      agammaglobulinemia.

PMID- 21738356
TI  - Chronic pruritus: clinics and treatment.
AB  - Chronic pruritus, one of the main symptoms in dermatology, is often intractable
      and has a high impact on patient's quality of life. Beyond dermatologic
      disorders, chronic pruritus is associated with systemic, neurologic as well as
      psychologic diseases. The pathogenesis of acute and chronic (>6 weeks duration)
      pruritus is complex and involves in the skin a network of resident (e.g., sensory
      neurons) and transient inflammatory cells (e.g., lymphocytes). In the skin,
      several classes of histamine-sensitive or histamine-insensitve C-fibers are
      involved in itch transmission. Specific receptors have been discovered on
      cutaneous and spinal neurons to be exclusively involved in the processing of
      pruritic signals. Chronic pruritus is notoriously difficult to treat. Newer
      insights into the underlying pathogenesis of pruritus have enabled novel
      treatment approaches that target the pruritus-specific pathophysiological
      mechanism. For example, neurokinin-1 antagonists have been found to relieve
      chronic pruritus.

PMID- 21738357
TI  - Treatment of Cultured Sebocytes with an EGFR Inhibitor Does Not Lead to
      Significant Upregulation of Inflammatory Biomarkers.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are being used to
      treat malignancies originating from epithelia. Unfortunately, blocking the EGFR
      pathway leads to various side effects, most frequently acneiform eruptions.
      OBJECTIVE: To probe the mechanism underlying this side effect, we investigated
      the effect of EGFR inhibitors on cultured sebocytes. METHODS: To examine the
      effects of an EGFR inhibitor (cetuximab, Erbitux(r) 10 ng/ml) and the effects of
      EGFR ligands, such as epidermal growth factor (EGF, 10 ng/ml) and transforming
      growth factor-alpha (TGF-alpha, 5 ng/ml), on the production of inflammatory
      cytokines in cultured sebocytes, we used reverse transcriptase-polymerase chain
      reaction, immunocytofluorescence and Western blots. Outcomes included the
      expression of interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-alpha),
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and EGFR. RESULTS:
      There were no significant differences in the expression of IL-1, IL-6, TNF-alpha,
      PPAR-gamma and EGFR between (a) groups treated with an EGFR inhibitor or an EGFR
      ligand and (b) the control group, except for a significant increase in the
      expression of IL-1 in the EGF-treated group. CONCLUSION: EGFR inhibitors and EGFR
      ligands do not provoke the expression of inflammatory biomarkers in cultured
      sebocytes. The role of the sebaceous glands in EGFR inhibitor-induced acneiform
      eruption should be investigated more thoroughly.

PMID- 21738358
TI  - The Expressions of TGF-beta(1) and IL-10 in Cultured Fibroblasts after ALA-IPL
      Photodynamic Treatment.
AB  - BACKGROUND: Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA)
      was originally used for treating superficial skin tumors. The application of PDT
      to other inflammatory dermatoses like acne vulgaris, psoriasis, granuloma
      annulare, localized scleroderma and lichen sclerosus has recently been
      introduced. However, the underlying mechanisms are not well understood. We've
      previously reported the induction of tumor growth factor (TGF)-beta(1) and
      interleukin (IL)-10 after PDT with ALA and intense pulsed light (IPL) in cultured
      HaCaT cells. OBJECTIVE: The purpose of this study was to investigate the
      expressions of TGF-beta(1) and IL-10 in cultured fibroblasts after PDT with using
      ALA and IPL. METHODS: Cultured fibroblasts were treated with ALA-IPL PDT (1umol/L
      of ALA; 0, 4, 8 and 12 J/cm(2) of IPL). The expressions of TGF-beta(1) and IL-10
      were investigated by reverse transcription-polymerase chain reaction and enzyme
      linked immunosorbent assay. RESULTS: TGF-beta(1) mRNA and protein were reduced
      down to 0.52- and 0.63-fold, respectively, after PDT and the IL-10 protein was
      increased up to 2.74-fold after PDT. CONCLUSION: The reduction of TGF-beta(1) was
      prominent after PDT and so an antisclerotic effect can be expected after PDT. The
      induction of IL-10 may contribute to the anti-inflammatory effect, which explains
      the therapeutic benefit of PDT for inflammatory dermatoses.

PMID- 21738359
TI  - Topical ALA-Photodynamic Therapy for Acne Can Induce Apoptosis of Sebocytes and
      Down-regulate Their TLR-2 and TLR-4 Expression.
AB  - BACKGROUND: Although photodynamic therapy (PDT) is widely performed for acne,
      little is known about its exact therapeutic mechanism. OBJECTIVE: We aimed to
      estimate the efficacy and safety of PDT on acne and to discover its mode of
      action. METHODS: We performed PDT on 12 patients with mild to moderate acne. The
      clinical efficacy was assessed by counting the acne lesions and measuring the
      sebum secretion before and after PDT. In addition, we took biopsy samples from
      the peri-lesional areas before and after 3-session of PDT. To examine the degree
      of apoptosis of the sebaceous follicles, TUNEL assay was performed. To
      investigate the changes of toll-like receptor (TLR)-2 and TLR-4 expression after
      PDT, immunohistochemical stainings were also carried out. Finally, we performed
      TUNEL assay using the cultured sebocytes to confirm the apoptosis of sebocytes in
      vitro after PDT. RESULTS: There was a significant reduction in the number of
      inflammatory acne lesions after PDT, compared to baseline (p<0.05). Sebum
      excretion significantly decreased 2 weeks after the first PDT session except for
      one patient (p<0.05). The TUNEL positive cells in the peri-lesional sebaceous
      glands after PDT markedly increased, compared with those of before PDT. A
      decrease in TLR-2 and TLR-4 expression by sebaceous glands and epidermis after
      PDT was 50% and 30%, respectively. CONCLUSION: Our results demonstrate that
      apoptosis of the sebaceous glands is associated with improvement of acne by PDT.
      PDT has shown to down-regulate TLR-2 and TLR-4 expression in the sebaceous glands
      and epidermis of acne patients.

PMID- 21738360
TI  - Expression of the c-Met Proteins in Malignant Skin Cancers.
AB  - BACKGROUND: The expression of c-Met is substantially elevated in most malignant
      human cancers. We therefore searched for c-Met expression and compared the
      expression level among malignant skin cancers. OBJECTIVE: The aim of this study
      was to determine the c-Met expression pattern and the protein expression level in
      selected malignant cutaneous tumors. METHODS: G361 cells (malignant melanoma cell
      line) and A431 cells (squamous cell carcinoma cell line) were cultured and
      analyzed, using immunoprecipitation and Western blot analysis, for expression of
      c-Met. Additionally, 16 separate specimens of malignant melanomas (MMs), 16
      squamous cell carcinomas (SCCs), 16 basal cell carcinomas (BCCs) and 16 normal
      tissues were analyzed for the expression of c-Met using immunohistochemical
      studies. RESULTS: Based on cultured cell immunoprecipitation and Western blot
      analysis, both A431 cells and G361 cells expressed c-Met, however, c-Met was
      expressed substantially more in G361 cells. Immunohistochemical examination of c
      Met showed that it was over-expressed in all malignant skin cancers. In addition,
      c-Met expression was more increased in MM compared to other cancers. CONCLUSION:
      In our study, c-Met is involved in malignant skin cancer development and the
      level of its expression is thought to be related to the degree of malignancy in
      melanoma cancers.

PMID- 21738361
TI  - Seroepidemiologic survey of varicella-zoster virus in korean adults using
      glycoprotein enzyme immuno assay and fluorescent antibody to membrane antigen
      test.
AB  - BACKGROUND: Herpes zoster (HZ) occurs mainly in the elderly and Korea is rapidly
      becoming an aging society. Therefore, it is important to know the immune status
      against varicella-zoster virus (VZV) in Korean adults to prevent the disease.
      OBJECTIVE: The aim of this study was to survey the immune status of Korean adults
      over 40 years of age against VZV. METHODS: Antibody titer was measured using a
      VaccZymeTM VZV glycoprotein enzyme immunoassay (gpEIA) (Binding Site, UK).
      Fluorescent antibody to membrane antigen (FAMA) test was performed to measure the
      seropositive rate. RESULTS: HZ incidence in the 214 adults enrolled in this study
      was 10.3%. The gpEIA geometric mean titer (GMT) was 490 mIU/ml and 90.2% of the
      subjects had a protective level of gpEIA antibody titer against varicella. The
      average gpEIA GMT of adults who previously had HZ was 1,122 mIU/ml, which was
      higher than the average gpEIA GMT of 457 mIU/ml in adults who had not had HZ. The
      FAMA positive rate was 98.6%. CONCLUSION: Most (90.2%) Korean adults >=40-years
      of-age have a protective level of gpEIA antibody against varicella and 98.6% were
      FAMA seropositive. The GMT of gpEIA antibody was significantly increased with
      age, and was higher in adults with a history of HZ.

PMID- 21738362
TI  - Characterizing cutaneous elastic fibers by eosin fluorescence detected by
      fluorescence microscopy.
AB  - BACKGROUND: Though elastic fibers are as important as collagen fibers in
      interpretation of the histopathologic findings, it is impossible to observe them
      on the hematoxylin & eosin (H&E) stained specimen. OBJECTIVE: Characterizing
      eosin fluorescence emitted by elastic fibers in H&E stained specimens. METHODS:
      Normal skin tissue sections were stained in 4 different ways (unstained,
      hematoxylin only, eosin only, H&E) and observed under a fluorescence microscope
      using a FITC filter set. Fluorescent findings of 30 H&E-stained specimens showing
      abnormal dermal findings were compared with bright field findings of Miller's
      elastic stained specimen. RESULTS: Strong eosin fluorescence was related to the
      differential binding property of eosin with elastic fibers. Hematoxylin stain
      quenched excessive eosin fluorescence from other tissue components and
      contributed to better contrast. Fluorescence microscopy of H&E-stained sections
      was found to be especially useful in observing mature elastic fibers in the
      reticular dermis. In 74% of the specimens, eosin fluorescence findings of elastic
      fibers in reticular dermis matched well with that of specimens with elastic fiber
      special stain. CONCLUSION: Analysis of skin elastic fibers by fluorescence
      microscopy is a useful and complementary method to reveal hidden elastic fibers
      in H&E-stained specimens.

PMID- 21738363
TI  - A Two-week Interval Is Better Than a Three-week Interval for Reducing the
      Recurrence Rate of Hand-foot Viral Warts after Cryotherapy: A Retrospective
      Review of 560 Hand-foot Viral Warts Patients.
AB  - BACKGROUND: Viral warts are a common infectious disease and liquid nitrogen
      cryotherapy is one of the most common methods for treatment of these warts. Hand
      foot viral warts frequently recur and reduce quality of life as well. OBJECTIVE:
      To find the ideal treatment interval between cryotherapy sessions that can
      influence not only the cure rate but also the recurrence rate for hand-foot viral
      warts. METHODS: A retrospective study was designed to compare a 2 week interval
      and a 3 week interval between cryotherapy sessions on hand-foot viral warts with
      respect to cure rate, recurrence rate, treatment number, duration of treatment,
      mean time to recurrence and adverse events. RESULTS: A total of 560 patients were
      enrolled. The overall cure rate was 75.7% and the recurrence rate was 19.6%. The
      mean time to recurrence was 7.8 months (range 1~26 months). For the 2-week and 3
      week groups, cure rates were, respectively, 76.6% (196) and 75.0% (228);
      recurrence rates were 13.3% (26) and 25.0% (57). The mean time to recurrence was
      9.8 months and 6.9 months, respectively. Adverse events were not statistically
      different. CONCLUSION: We suggested that 2-week cryotherapy is optimal not only
      because of the rapid cure but also because of the lower recurrence rate and
      similar adverse events.

PMID- 21738364
TI  - A Case of Lichen Planus Pigmentosus-inversus in a Korean Patient.
AB  - Lichen planus pigmentosus-inversus is a rare variant of lichen planus
      pigmentosus. The eruption of lichen planus pigmentosus-inversus occurs mainly in
      the flexural regions and presents with brownish macules and patches. Here we
      describe the case of a 31-year-old Korean woman who presented with hyperpigmented
      lesions over her antecubital and popliteal area and groin. Physical examination
      revealed multiple brownish macules and patches on the intertriginous area without
      pruritis, and histologic findings showed a regressive pattern of lichen planus.
      These clinical and histological findings were consistent with a diagnosis of
      lichen planus pigmentosus-inversus.

PMID- 21738365
TI  - Giant acquired digital fibrokeratoma occurring on the left great toe.
AB  - Acquired digital fibrokeratoma is an uncommon, benign fibrous tumor which usually
      occurs in adults as a solitary lesion. The most frequent locations are fingers
      and toes and the size of the tumor is generally small, around 3~5 mm. An 18-year
      old female presented with a solitary, skin-colored, round and protruded nodule of
      the left great toe. The size of nodule was 2.5*1.6*1.4 cm. Histopathologic
      examination revealed typical findings of acquired digital fibrokeratoma. Herein,
      we report a giant acquired digital fibrokeratoma.

PMID- 21738366
TI  - A herpes simplex virus infection secondary to acupuncture and cupping.
AB  - Acupuncture and cupping have a public reputation as being safe even though these
      practices can lead to complications such as trauma or infection. We report here
      on a case of herpes simplex virus (HSV) infection secondary to acupuncture and
      cupping in a 56-year-old woman. The patient, who had a history of acupuncture and
      cupping on her left forearm for treating her myalgia, developed painful papules.
      Histologically, the biopsy specimen showed characteristic ballooning degeneration
      and inclusion bodies in the epidermis and mid-dermis. These clinical and
      histological findings were consistent with the diagnosis of HSV infection.

PMID- 21738367
TI  - A case of reactive eccrine syringofibroadenoma.
AB  - Eccrine syringofibroadenoma is a rare adnexal tumor of eccrine ductal
      differentiation with variable clinical features. It manifests as either a
      solitary or multiple papules and nodules arranged in a symmetrical or linear
      pattern. The anatomical distribution is wide and includes the face, trunk,
      extremities, and rarely the nails. Histopathological findings show anastomosing
      cords and strands of uniform cuboidal cells surrounded by fibrovascular stroma.
      Herein, we report a case of reactive eccrine syringofibroadenoma which developed
      on the foot of a 37-year-old woman, after self-paring of tissue and subsequent
      infection and ulceration.

PMID- 21738368
TI  - Pigmented mammary paget disease with reticulated features: a rare variant of
      mammary paget disease.
AB  - Pigmented mammary Paget disease (PMPD) is a rare subtype of mammary Paget disease
      that presents as a hyperpigmented patch or plaque over the areola and nipple. We
      herein report on an unusual case of PMPD with reticulated features in a 98-year
      old female. The histology showed intraepidermal pagetoid cells containing melanin
      pigments without any underlying intraductal carcinoma.

PMID- 21738369
TI  - A Case of Primary Cutaneous CD4 Positive Small/medium T Cell Lymphoma.
AB  - Primary cutaneous CD4 positive small/medium T cell lymphoma (PCSM-TCL) is a
      provisional entity in the new WHO-EORTC classification for cutaneous lymphoma,
      and it is a rare disease with a favorable clinical course. PCSM-TCL may present
      with different clinical and pathologic features associated with the biologic
      behavior of the disease. Herein we report on a 63-year-old woman with multiple,
      multifocal, erythematous to violaceous papules and plaques that progressed
      despite local radiotherapy.

PMID- 21738370
TI  - Two cases of eosinophilic fasciitis.
AB  - Eosinophic fasciitis (EF) is an uncommon connective tissue disease characterized
      by scleroderma-like cutaneous changes, peripheral eosinophilia,
      hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate (ESR).
      Typical histopathologic findings include chronic inflammatory infiltration
      affecting the deep fascia with lymphocytes, histiocytes, and occasionally
      eosinophils. We report two cases of EF, the first of which is a 36-year-old man
      with a tender brownish induration on both forearms, for 2 months. Histopathologic
      examination showed fibrotic fascia with a mixed inflammatory cell infiltration.
      The second case is a 52-year-old woman with a symmetrical painful swelling and
      skin induration on both forearms, for 4 months. A deep biopsy demonstrated
      chronic inflammatory cell infiltration and hyaline degeneration in the fascia.
      Increased signal intensity in the fascia and tendon sheath was shown on magnetic
      resonance imaging. In laboratory examination, mild eosinophilia was found in both
      cases. Both patients had a history of physical activity (weight training and
      excessive housework, respectively) and showed marked improvement with high doses
      of oral prednisolone for several months.

PMID- 21738371
TI  - Systemic contact dermatitis from propolis ingestion.
AB  - Propolis, also known as bee glue, is a substance collected by worker bees and it
      is used as a material for constructing and maintaining their beehives. It has
      been used topically and orally by humans for its anti-inflammatory properties.
      However, the growing use of propolis has been paralleled by reports of allergic
      contact dermatitis as a reaction to the substance. Contact dermatitis with
      generalized cutaneous manifestations elicited by propolis ingestion has not been
      previously reported. Here we report on the first case of systemic contact
      dermatitis from propolis ingestion in a 36-year-old woman.

PMID- 21738372
TI  - A case of cutaneous horn originating from keratoacanthoma.
AB  - Cutaneous horn is the clinical description of a hyperproliferation of compact
      keratin in response to a wide array of underlying benign and malignant pathologic
      changes. We report here on a case of cutaneous horn that originated from
      keratoacanthoma in a 76-year-old woman. Grossly, a 2.5*0.7 cm sized yellow-white
      colored scaly fungating mass from an erythematous nodule was observed on the
      right temporal area. Histopathologically, it was reported as keratoacanthoma with
      cutaneous horn. The lesion was totally excised after the diagnosis.

PMID- 21738373
TI  - Precalcaneal congenital fibrolipomatous hamartoma.
AB  - Precalcaneal congenital fibrolipomatous hamartomas (PCFHs) are characterized
      clinically by the presence of unilateral or bilateral, asymptomatic nodules in
      the medial precalcaneal plantar region of the heel. They are skin colored and
      usually painless nodules. In most patients, the lesions appear within the first
      few months of life, but they may also be present at birth. Generally PCFHs are
      benign, but they can grow in proportion to the growth of the infants. Here, we
      report the case of a 4-month-old boy with a solitary, localized skin-colored
      nodule on the precalcaneal plantar region of his right heel, diagnosed as a PCFH.

PMID- 21738374
TI  - Unilateral nevoid acanthosis nigricans with a submammary location.
AB  - Unilateral nevoid acanthosis nigricans (AN) is an exceedingly rare form of AN,
      which is a benign disorder of keratinization. The lesions of unilateral nevoid AN
      are distributed unilaterally while the histopathologic findings are similar to
      the common form of AN, and this is characterized by hyperkeratosis,
      papillomatosis and moderate acanthosis. A 19-year-old female presented with
      asymptomatic brownish pigmented plaques on the medial side of the left submammary
      area. Based on her clinical and histopathologic findings, a diagnosis of
      unilateral nevoid AN was made. She was treated with topical tretinoin and her
      skin lesions were almost cleared 9 months after her first visit to our clinic.
      Various previous reports have described the localization of this disorder, but
      there has been no previous case report with the clinical manifestations on the
      unilateral submammary area. Therefore, we herein report the first case of
      unilateral nevoid AN with an unusual submammary location.

PMID- 21738375
TI  - Warty dyskeratoma involving two adjoining follicles.
AB  - Warty dyskeratoma (WD) is a rare epidermal tumor that frequently arises as a
      papule or nodule on the head or neck of middle-aged or older persons.
      Histologically, it shows a cup-shaped keratin-filled invagination of an
      acanthotic epidermis, suprabasilar clefting with villi projecting into the clefts
      and acantholytic dyskeratotic cells are also present. The changes almost always
      involve a single hair follicle. We describe a distinctive case of WD that showed
      involvement of two adjoining follicles within a solitary lesion.

PMID- 21738376
TI  - A case of metastatic squamous cell carcinoma arising from actinic cheilitis.
AB  - Actinic keratosis (AK) is a common, sun-induced, pre-malignant lesion with a
      strong likelihood of progressing to a malignancy. The reported risk of AK
      progressing to squamous cell carcinoma (SCC) varies from less than 1% to 20%.
      Clinically, induration, pain, large size, marked hyperkeratosis, ulceration,
      bleeding, rapid growth, and recurrence or persistence may be markers of AK
      progression into SCC. The risk of SCC metastasizing ranges between 0.5% and 3%.
      However, SCC of the lip arising from actinic cheilitis is more prone to
      metastasis than cutaneous SCC, with rates of the former varying between 3% and
      20%. Here we report a typical case of SCC from actinic cheilitis with metastasis
      to the lymph nodes during a 4-year follow-up period. To exclude SCC, we emphasize
      the need for regular follow-up and prompt evaluation, including careful
      pathologic examination for actinic cheilitis.

PMID- 21738377
TI  - CD8+ Lymphomatoid Papulosis.
AB  - Lymphomatoid papulosis (LyP) is defined as a histologically malignant, but
      clinically benign condition. It can appear as erythematous pink to purple papules
      or nodules. Immunophenotyping studies of the lymphomatoid papulosis lesions have
      shown a predominance of a CD4 expression and negativity for CD8. However, a
      positive CD8 expression has rarely been reported for LyP. Herein we report on a
      case of CD8 positive lymphomatoid papulosis in a 43-year-old man. The patient
      presented with erythematous, asymptomatic papules on the left axilla and thigh.
      Histopathologically, there was a wedge-shaped infiltrate composed of a mixture of
      various cell types, including lymphocytes, histiocytes, neutrophils and large
      atypical lymphoid cells. Immunophenotyping revealed the neoplastic cells were
      positive for CD3, CD8 and CD30 and they were negative for CD4, CD20 and CD56.

PMID- 21738378
TI  - Acute generalized exanthematous pustulosis caused by diltiazem.
AB  - Acute generalized exanthematous pustulosis is clinically characterized by fever,
      pruritus and an acute pustular eruption. It can be described as having an abrupt
      onset and then spontaneous resolution occurs shortly after the start of symptoms,
      and there is usually only a single episode. Most cases have been triggered by the
      ingestion of drugs. Diltiazem hydrochloride is a calcium channel blocker that is
      commonly used for treating hypertension and angina. This drug was found to be the
      responsible agent in our current patient. There have been 9 such case reports in
      the English medical literature, yet this is the first such report in the Korean
      medical literature. We present the case of a 51-year-old male who experienced an
      acute generalized exanthematous pustulosis due to diltiazem hydrochloride and we
      review the relevant literature.

PMID- 21738379
TI  - Branch-shaped Cutaneous Hypopigmentation and Atrophy after Intralesional
      Triamcinolone Injection.
AB  - Cutaneous changes after local corticosteroid administration may include dermal
      atrophy, hyperpigmentation, alopecia, and hypopigmentation. Linear
      hypopigmentation and atrophy after intralesional injection of triamcinolone
      acetonide has been reported in the literature as a very rare side effect. A 30
      year-old woman visited our dermatology department for a linear hypopigmented
      patch with atrophy from her left foot to the lower margin of the knee. The lesion
      developed after injection of an intralesional corticosteroid. The patient was
      diagnosed with linear hypopigmentation and atrophy secondary to the triamcinolone
      injection.

PMID- 21738380
TI  - Four cases of lobulated intradermal nevus: a sign of aging melanocytic nevus.
AB  - Melanocytic nevi are subject to change with age in both clinical and
      histopathologic findings. In 1991, Cho et al. first reported three cases of
      lobulated intradermal nevi and suggested their cases represented an unusual form
      of regressing melanocytic nevus. Herein we report four cases of lobulated
      intradermal nevus and review previous literature.

PMID- 21738381
TI  - Sorafenib (Nexavar(r), BAY 43-9006)-induced Hand-foot Skin Reaction with Facial
      Erythema.
AB  - Sorafenib (Nexavar(r), BAY 43-9006) is a novel, orally administered multi-kinase
      inhibitor that has recently been approved for the treatment of metastatic renal
      cell carcinoma. It is also used to delay disease progression in patients with
      advanced solid organ malignancies and metastatic melanoma. Sorafenib is
      associated with a relatively high incidence of dermatologic adverse events. The
      commonly occurring dermatologic adverse events associated with sorafenib include
      hand-foot skin reaction, facial erythema, splinter subungual hemorrhages,
      alopecia, pruritus and xerosis. We report here on a case of a 50-year-old man who
      was diagnosed with metastatic hepatocellular carcinoma. He developed both facial
      erythema and hand-foot skin reaction after the administration of sorafenib.

PMID- 21738382
TI  - A rapidly regressing wart following biopsy.

PMID- 21738383
TI  - Signal and image processing techniques for functional near-infrared imaging of
      the human brain.
AB  - Near-infrared spectro-imaging (NIRSI) is a quickly developing method for the in
      vivo imaging of biological tissues. In particular, it is now extensively employed
      for imaging the human brain. In this non-invasive technique, the information
      about the brain is obtained from the analysis of spatial light bundles formed by
      the photons traveling from light sources to detectors placed on the surface of
      the head. Most significant problems in the functional brain NIRSI are the
      separation of the brain information from the physiological noise in non-cerebral
      tissues, and the localization of functional signals. In this paper we describe
      signal and image processing techniques we developed in order to measure two types
      of functional cerebral signals: the hemodynamic responses, and neuronal
      responses.

PMID- 21738384
TI  - Quantification of Three Dimensional Tongue Motion During Speech Using zHARP.
AB  - To understand the role of the tongue in speech production, it is desirable to
      directly image the motion and strain of the muscles within the tongue. Magnetic
      resonance tagging-which was originally developed for cardiac imaging-has
      previously been applied to image both two-dimensional and three-dimensional
      tongue motion during speech. However, to quantify three-dimensional motion and
      strain, multiple images yielding two-dimensional motion must be acquired at
      different orientations and then interpolated-a time-consuming task both in image
      acquisition and processing. Recently, a new MR imaging and image processing
      method called zHARP was developed to encode and track 3D motion from a single
      slice without increasing acquisition time. zHARP was originally developed and
      applied to cardiac imaging. The application of zHARP to the tongue is not
      straightforward because the tongue in repetitive speech does not move as
      consistently as the heart in its beating cycle. Therefore tongue images are more
      susceptible to motion artifacts. Moreover, these artifacts are greatly
      exaggerated as compared to conventional tagging because of the nature of zHARP
      acquisition. In this work, we re-implemented the zHARP imaging sequence and
      optimized it for the tongue motion analysis. We also optimized image acquisition
      by designing and developing a specialized MRI scanner triggering method and vocal
      repetition to better synchronize speech repetitions. Our method was validated
      using a moving phantom. Results of 3D motion tracking and strain analysis on the
      tongue experiments demonstrate the effectiveness of this method.

PMID- 21738385
TI  - Removing Shape-Preserving Transformations in Square-Root Elastic (SRE) Framework
      for Shape Analysis of Curves.
AB  - This paper illustrates and extends an efficient framework, called the square-root
      elastic (SRE) framework, for studying shapes of closed curves, that was first
      introduced in [2]. This framework combines the strengths of two important ideas -
      elastic shape metric and path-straightening methods - for finding geodesics in
      shape spaces of curves. The elastic metric allows for optimal matching of
      features between curves while path-straightening ensures that the algorithm
      results in geodesic paths. This paper extends this framework by removing two
      important shape preserving transformations: rotations and re-parameterizations,
      by forming quotient spaces and constructing geodesics on these quotient spaces.
      These ideas are demonstrated using experiments involving 2D and 3D curves.

PMID- 21738386
TI  - PKCdelta-dependent signaling mediates ethambutol-induced toxic effects on human
      retinal pigment cells.
AB  - PURPOSE: Our previous report demonstrated that ethambutol (EMB) might induce
      cytoplasmic vacuolization and reduce the uptake of photoreceptor rod outer
      segments (ROS) in retinal pigment epithelium (RPE) cells, which are mediated via
      a protein kinase C (PKC)-dependent pathway. In the present study, we sought to
      identify the PKC isozyme(s) involved. METHODS: EMB-induced cytoplasmic
      vacuolization and uptake of ROS were observed under a phase contrast microscope.
      Western blots were performed to observe the membrane translocation of PKC
      isozymes and cytoplasmic release of cathepsin D. Quantitative PCR were performed
      to analyze gene expression of PKCdelta. Human RPE cell line RPE50 and ARPE19
      cells were pretreated with specific inhibitors or transfected with shRNAs of
      various PKC isozymes, including PKCalpha, beta, epsilon, gamma, and delta, to
      examine whether EMB-induced toxic effects were prevented. RESULTS: In RPE50
      cells, gene expression of PKCdelta on both mRNA and protein levels was induced by
      EMB within 30 min to 3 h. EMB-induced cytoplasmic vacuolization in both RPE50 and
      ARPE19 cells was prevented by pretreating the cells with a specific inhibitor of
      PKCdelta, Rottlerin, or depletion of PKCdelta by shRNA. EMB-triggered reduction
      of ROS uptake was also significantly suppressed by pretreatment with Rottlerin,
      or depletion of PKCdelta by shRNA technology. In contrast, pretreatment of the
      cells with specific inhibitors of PKCalpha, beta, epsilon, or gamma, or depletion
      of PKCalpha or beta didn't influence the aforementioned EMB-triggered toxic
      effects. In addition, in RPE50, EMB induced the release of lysosomal enzyme
      cathepsin D into cytosol within 30 min to 6 h, which was also prevented by
      Rottlerin. CONCLUSIONS: EMB-induced vacuole formation, cytoplasmic release of
      cathepsin D, and reduction of phagocytosis in RPE are intimately correlated and
      regulated by the PKCdelta signal pathway.

PMID- 21738387
TI  - Expression of vascular endothelial growth factor and pigment epithelial-derived
      factor in a rat model of retinopathy of prematurity.
AB  - OBJECTIVE: To determine the effects of oxygen fluctuations on pigment epithelial
      derived factor (PEDF) and vascular endothelial growth factor (VEGF)/PEDF ratios
      in a relevant rat model of retinopathy of prematurity (ROP). METHODS: The
      expression of retinal PEDF mRNA and of VEGF and PEDF protein were determined
      using real-time polymerase chain reaction or enzyme-linked immunosorbent assays
      at different postnatal day ages for rat pups raised in room air (RA) or in a rat
      model mimicking ROP. Statistical outcomes were determined with factorial analyses
      of variance. Mean VEGF and PEDF protein levels were determined at different ages
      for rats in the ROP model and for RA-raised rats, and the ratio of VEGF/PEDF
      protein versus age was plotted. At postnatal day (P) 14, inner retinal plexus
      vascularization had extended to the ora serrata in pups raised in RA. In the ROP
      model, avascular retina persisted at P14 and intravitreous neovascularization
      developed at P18. Therefore, VEGF and PEDF expression was determined in the ROP
      model and in RA-raised rat pups at P14 and P18. RESULTS: Older age was associated
      with increased PEDF mRNA (p<0.001), PEDF protein (p=0.005), and VEGF protein
      (p=0.005), and VEGF protein (p<0.0001). Exposure to fluctuations of oxygen in the
      50/10 oxygen-induced retinopathy model compared to RA was associated with
      increased PEDF mRNA (p=0.0185), PEDF protein (p<0.0001), or VEGF protein
      (p<0.0001). The VEGF/PEDF ratio favored angiogenic inhibition (<1.0) before but
      not on P14, when avascular retina persisted in the ROP model but not in RA. The
      VEGF/PEDF ratio favored angiogenesis (>1.0) at P14 and P 18 when intravitreous
      neovascularization occurred in the ROP model. CONCLUSIONS: Increased expression
      levels of VEGF and PEDF are associated with older postnatal day age or with
      exposure to fluctuations in oxygen in the 50/10 oxygen-induced retinopathy model
      compared to RA. PEDF protein more closely associates with avascular retinal
      features and neovascularization than does VEGF protein or the VEGF/PEDF in the
      ROP model. Although PEDF has been proposed as a potential treatment in ROP,
      interventional studies using PEDF in an ROP model to potentially reduce
      intravitreous neovascularization are required to determine timing, efficacy, and
      dose of PEDF.

PMID- 21738388
TI  - Complement gene expression and regulation in mouse retina and retinal pigment
      epithelium/choroid.
AB  - PURPOSE: To understand the expression of genes involved in different complement
      pathways in the retina and retinal pigment epithelium (RPE)/choroid under
      physiologic conditions and how their expression is regulated by inflammatory
      cytokines. METHODS: The expression of complement components of the classical
      pathway (CP), mannose-binding lectin (MBL) pathway, alternative pathway (AP), and
      terminal pathway in the retina and RPE/choroid was determined by conventional
      reverse transcription polymerase chain reaction (RT-PCR). The effect of
      inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha, 20 ng/ml),
      interleukin (IL)-6 (10 ng/ml), interferon-gamma (IFN-gamma, 100 ng/ml) or
      lipopolysaccharides (LPS, 1 MUg/ml) on the expression of these complement
      component genes was tested in vitro in primary cultured RPE cells and a
      microglial cell line (BV2 cells) and quantified by real-time RT-PCR. RESULTS: In
      the CP, complements C1qb, C1r, C1s, C2, and C4 were constitutively expressed by
      retina and RPE/choroid. Complement factor H and factor B of the AP as well as C3
      were also detected in the retinal and RPE/choroidal tissues. In the MBL pathway,
      low levels of mannose-binding lectin (MBL)-associated serine protease (MASP)-1 in
      the retina and RPE/choroid and MASP2L in the retina were detected. Other
      components, including mannose-binding lectin 1 (MBL1), mannose-binding lectin 2
      (MBL2), complement factor I (CFI), complement component 5 (C5) and complement
      factor H-related protein 1 (CFHR1), were not detected in either the retina or the
      RPE/choroid. The expression of CP- and AP-complement component genes in RPE and
      microglial cells was upregulated by interferon (IFN)-gamma treatment. Treatment
      with TNF-alpha selectively upregulated the expression of C1s and C3 genes but
      downregulated complement factor H gene expression in RPE and microglial cells.
      The expression of genes involved in the MBL pathway was not affected by the
      inflammatory cytokines tested in this study. CONCLUSIONS: Retina and RPE/choroid
      express a variety of complement components that are involved mainly in the CP and
      AP. RPE and microglial cells are the main sources of retinal complement gene
      expression. Retinal complement gene expression is regulated by inflammatory
      cytokines, such as IFN-gamma and TNF-alpha.

PMID- 21738389
TI  - A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable
      degrees of auditory loss in a consanguineous Portuguese family.
AB  - PURPOSE: To identify the genetic defect of a consanguineous Portuguese family
      with rod-cone dystrophy and varying degrees of decreased audition. METHODS: A
      detailed ophthalmic and auditory examination was performed on a Portuguese
      patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects
      were excluded by performing autosomal recessive retinitis pigmentosa (arRP)
      genotyping microarray analysis and by Sanger sequencing of the coding exons and
      flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2
      open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping
      was performed in DNA samples from available family members using a 700K single
      nucleotide polymorphism (SNP) microarray. Candidate genes present in the
      significantly large homozygous regions were screened for mutations using Sanger
      sequencing. RESULTS: The largest homozygous region (~11 Mb) in the affected
      family members was mapped to chromosome 9, which harbors deafness, autosomal
      recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation
      analysis of DFNB31 in the index patient identified a novel one-base-pair deletion
      (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13)
      and co-segregated with the disease in the family. Ophthalmic examination of the
      index patient and the affected siblings showed severe rod-cone dystrophy. Pure
      tone audiometry revealed a moderate hearing loss in the index patient, whereas
      the affected siblings were reported with more profound and early onset hearing
      impairment. CONCLUSIONS: We report a novel truncating mutation in DFNB31
      associated with severe rod-cone dystrophy and varying degrees of hearing
      impairment in a consanguineous family of Portuguese origin. This is the second
      report of DFNB31 implication in Usher type 2.

PMID- 21738390
TI  - Clinical evaluation of two consanguineous families with homozygous mutations in
      BEST1.
AB  - PURPOSE: To describe the clinical and genetic findings in two consanguineous
      families with Best vitelliform macular dystrophy (BVMD) and homozygous mutations
      in the bestrophin-1 (BEST1) gene. METHODS: Ophthalmologic examination was
      performed in eight members of two families originating from Spain and Denmark.
      Mutation screening was performed using the Vitelliform Macular Dystrophy mutation
      array from Asper Biotech, and by the directed genomic sequencing of BEST1.
      RESULTS: Two homozygous mutations were detected in these families. Mutation
      c.936C>A (p.Asp312Glu) has been reported previously in a Danish family; here, we
      describe four additional individuals in this family demonstrating findings
      compatible with a severe dominant BVMD, albeit with reduced penetrance in
      heterozygotes. In the Spanish family, a novel homozygous missense mutation in
      exon 4, c.388 C>A (p.Arg130Ser), was identified in the siblings. Homozygous
      siblings demonstrated evidence of multifocal vitelliform retinopathy, whereas
      heterozygous family members presented findings ranging from isolated reduction of
      the electrooculogram Arden ratio to normal values on all clinical parameters.
      CONCLUSIONS: As demonstrated in these consanguineous families, a great clinical
      variability is associated with homozygous mutations in BEST1, ranging from severe
      dominant BVMD with reduced penetrance in heterozygotes to autosomal recessive
      bestrophinopathy.

PMID- 21738391
TI  - Differential expression of proteins in monozygotic twins with discordance of
      infantile esotropic phenotypes.
AB  - PURPOSE: To identify strabismus-related proteins, we performed proteome analysis
      in monozygotic twins with discordance of congenital esotropic phenotypes and in
      normal children. METHODS: Surface-enhanced laser desorption/ ionization time-of
      flight mass spectrometry (SELDI-TOF-MS) technology was used to detect changes in
      protein expression in a pair of twins with discordant esotropic phenotypes (twin
      A is orthotropic and twin B is esotropic). In addition, two non-twin esotropic
      children and two orthotropic children of the same age were chosen. The
      differentially expressed proteome obtained was validated in twelve non-twin
      esotropic children and eighteen orthotropic children and compared to the protein
      database. RESULTS: We detected four differentially expressed proteins in
      monozygotic twins with discordance of congenital esotropic phenotypes. The
      corresponding molecular weights were 4,146 Da, 4,801 Da, 7,786 Da, and 5,859 Da,
      respectively. Among these 4 proteins, the first three proteins were down
      regulated and the last was upregulated. The initial characterization of these
      detected proteins via protein library revealed that their characteristics were
      similar to those of the glucagon precursor, pituitary adenylate cyclase
      activating polypeptide (PACAP), camp-dependent protein kinase inhibitor alpha,
      and anti-metastasis gene (antigen), respectively. CONCLUSIONS: There were
      differentially expressed proteins between monozygotic twins with discordance of
      congenital esotropic phenotypes and normal children. These differentially
      expressed proteins were mainly down-regulated in the strabismus patients and may
      be involved in the occurrence and development of congenital esotropia.

PMID- 21738392
TI  - Chromosome abnormalities and the genetics of congenital corneal opacification.
AB  - Congenital corneal opacification (CCO) encompasses a broad spectrum of disorders
      that have different etiologies, including genetic and environmental. Terminology
      used in clinical phenotyping is commonly not specific enough to describe separate
      entities, for example both the terms Peters anomaly and sclerocornea have been
      ascribed to a clinical picture of total CCO, without investigating the presence
      or absence of iridocorneal adhesions. This is not only confusing but also
      unhelpful in determining valid genotype-phenotype correlations, and thereby
      revealing clues for pathogenesis. We undertook a systematic review of the
      literature focusing on CCO as part of anterior segment developmental anomalies
      (ASDA), and analyzed its association specifically with chromosomal abnormalities.
      Genes previously identified as being associated with CCO are also summarized. All
      reports were critically appraised to classify phenotypes according to described
      features, rather than the given diagnosis. Some interesting associations were
      found, and are discussed.

PMID- 21738393
TI  - Dissecting the genetic heterogeneity of myopia susceptibility in an Ashkenazi
      Jewish population using ordered subset analysis.
AB  - PURPOSE: Despite many years of research, most of the genetic factors contributing
      to myopia development remain unknown. Genetic studies have pointed to a strong
      inherited component, but although many candidate regions have been implicated,
      few genes have been positively identified. METHODS: We have previously reported 2
      genomewide linkage scans in a population of 63 highly aggregated Ashkenazi Jewish
      families that identified a locus on chromosome 22. Here we used ordered subset
      analysis (OSA), conditioned on non-parametric linkage to chromosome 22 to detect
      other chromosomal regions which had evidence of linkage to myopia in subsets of
      the families, but not the overall sample. RESULTS: Strong evidence of linkage to
      a 19-cM linkage interval with a peak OSA nonparametric allele-sharing logarithm
      of-odds (LOD) score of 3.14 on 20p12-q11.1 (DeltaLOD=2.39, empirical p=0.029) was
      identified in a subset of 20 families that also exhibited strong evidence of
      linkage to chromosome 22. One other locus also presented with suggestive LOD
      scores >2.0 on chromosome 11p14-q14 and one locus on chromosome 6q22-q24 had an
      OSA LOD score=1.76 (DeltaLOD=1.65, empirical p=0.02). CONCLUSIONS: The chromosome
      6 and 20 loci are entirely novel and appear linked in a subset of families whose
      myopia is known to be linked to chromosome 22. The chromosome 11 locus overlaps
      with the known Myopia-7 (MYP7, OMIM 609256) locus. Using ordered subset analysis
      allows us to find additional loci linked to myopia in subsets of families, and
      underlines the complex genetic heterogeneity of myopia even in highly aggregated
      families and genetically isolated populations such as the Ashkenazi Jews.

PMID- 21738394
TI  - Keratin 13 is a more specific marker of conjunctival epithelium than keratin 19.
AB  - PURPOSE: To evaluate the expression patterns of cytokeratin (K) 12, 13, and 19 in
      normal epithelium of the human ocular surface to determine whether K13 could be
      used as a marker for conjunctival epithelium. METHODS: Total RNA was isolated
      from the human conjunctiva and central cornea. Those transcripts that had
      threefolds or higher expression levels in the conjunctiva than the cornea were
      identified using microarray technique. Expression levels of three known signature
      genes and of two conjunctival genes, K13 and K19 were confirmed by using
      quantitative real-time PCR (qRT-PCR). Protein expression of K12, K13, and K19 was
      confirmed by immunostaining with specific antibodies on histologic sections of
      human sclerocornea that contained the conjunctiva, limbus, and cornea and on
      impression cytology (IC) specimens of the cornea and conjunctiva from normal
      donors. Double staining of K13/K12 and K19/K12 on histologic sections and IC
      specimens was performed. RESULTS: There were 337 transcripts that were
      preferentially expressed in the conjunctiva. K13 and K19 were among the top
      twenty transcripts in the conjunctiva and this preferential expression pattern of
      K13 and K19 was confirmed by qRT-PCR. Immunohistochemical studies showed that K13
      was expressed at the posterior limbal epithelium and conjunctival epithelium but
      was totally absent in the cornea. K12 was expressed in the corneal and anterior
      limbal epithelia except for the basal layer and was absent from the conjunctiva.
      In contrast, K19 was detected in the corneal, limbal and conjunctival epithelia.
      Immunostaining of the IC specimens showed K12(+) epithelial cells in the corneal
      region, K13(+) cells in the conjunctival area, and K19(+) cells in the corneal
      and conjunctival specimens. Expression of K13 and K12 on the ocular surface was
      mutually exclusive on both the histologic and IC samples using double
      immunostaining. CONCLUSIONS: K13 is more specific to the conjunctival epithelial
      cells than K19 and potentially could be used as a marker to identify conjunctival
      epithelial cells in limbal stem cell deficiency.

PMID- 21738395
TI  - Molecular epidemiology of Usher syndrome in Italy.
AB  - PURPOSE: Usher syndrome is an autosomal recessive disorder characterized by
      hearing and vision loss. Usher syndrome is divided into three clinical subclasses
      (type 1, type 2, and type 3), which differ in terms of the severity and
      progression of hearing loss and the presence or absence of vestibular symptoms.
      Usher syndrome is defined by significant genetic heterogeneity, with at least 12
      distinct loci described and 9 genes identified. This study aims to provide a
      molecular epidemiology report of Usher syndrome in Italy. METHODS: Molecular data
      have been obtained on 75 unrelated Italian patients using the most up-to date
      technology available for the screening of Usher syndrome gene mutations, i.e.,
      the genotyping microarray developed by Asper Biotech (Tartu, Estonia), which
      simultaneously investigates 612 different marker positions using the well
      established arrayed primer extension methodology (APEX). RESULTS: Using this
      method, we found that 12% of cases (9 out of 75) harbored homozygous or compound
      heterozygous mutations in the gene positions analyzed, whereas 20% (15 out of 75)
      of the patients were characterized by the presence of only one mutated allele
      based on the positions analyzed. One patient was found to be compound
      heterozygous for mutations in two different genes and this represents an example
      of possible digenic inheritance in Usher syndrome. A total of 66.6% of cases (50
      out of 75) were found to be completely negative for the presence of Usher
      syndrome gene mutations in the detected positions. Mutations detected by the
      array were confirmed by direct sequencing. CONCLUSIONS: These findings highlight
      the efficacy of the APEX-based genotyping approach in the molecular assessment of
      Usher patients, suggesting the presence of alleles not yet identified and/or the
      involvement of additional putative genes that may account for the pathogenesis of
      Usher syndrome.

PMID- 21738396
TI  - A new VCAN/versican splice acceptor site mutation in a French Wagner family
      associated with vascular and inflammatory ocular features.
AB  - PURPOSE: To detail the highly variable ocular phenotypes of a French family
      affected with an autosomal dominantly inherited vitreoretinopathy and to identify
      the disease gene. METHODS: Sixteen family members with ten affected individuals
      underwent detailed ophthalmic evaluation. Genetic linkage analysis and gene
      screening were undertaken for genes known to be involved in degenerative and
      exudative vitreoretinopathies. Qualitative reverse transcriptase-PCR analysis of
      the versiscan (VCAN) transcripts was performed after mutation detection in the
      VCAN gene. RESULTS: The first index patient of this French family was referred to
      us because of a chronic uveitis since infancy; this uveitis was associated with
      exudative retinal detachment in the context of a severe uncharacterized familial
      vitreoretinopathy. Genetic linkage was obtained to the VCAN locus, and we further
      identified a new pathogenic mutation at the highly conserved splice acceptor site
      in intron 7 of the VCAN gene (c.4004-2A>T), which produced aberrantly spliced
      VCAN transcripts. CONCLUSIONS: Extensive molecular investigation allowed us to
      classify this familial vitreoretinopathy as Wagner syndrome. This study
      illustrates the need to confirm clinical diagnosis by molecular genetic testing
      and adds new ocular phenotypes to the Wagner syndrome, such as vascular and
      inflammatory features.

PMID- 21738397
TI  - Is the GSTM1 null polymorphism a risk factor in primary open angle glaucoma?
AB  - PURPOSE: To investigate the association of glutathione S-transferase (GST) GSTM1,
      GSTT1, and GSTP1 genes with the risk of primary open angle glaucoma (POAG) and
      clinical features of the disease. METHODS: We conducted a case-control study that
      included 87 Brazilian patients with POAG and 85 healthy controls matched for age,
      ethnicity, and sex, whose blood samples were genotyped for polymorphisms in GST
      genes using polymerase chain reaction (PCR) based methods. RESULTS: The GSTM1
      null polymorphism was significantly more common in the POAG than in the controls
      group (OR: 2.1, 95% CI: 1.13-3.9; p=0.018). The combined GSTM1 null/GSTT1+
      genotype and GSTM1 null/GSTP1 Ile/Val or Val/Val was more prevalent in POAG
      patients, being a risk factor for POAG (OR: 2.4, 95% CI: 1.16-4.9; p=0.016 and
      OR: 2.7, 95% CI: 1.07-6.74; p=0.033, respectively). The GSTM1 null/GSTT1+
      genotype were associated with higher levels of IOP of both eyes and with more
      severe defect of the right eye optic nerve. The GSTM1 null/GSTP1 Ile/Val or
      Val/Val genotypes were associated with higher levels of IOP and more advanced
      defect of the right eye optic nerve and visual field. CONCLUSIONS: We demonstrate
      that GSTM1 null polymorphism is associated with POAG in the Brazilian population.

PMID- 21738398
TI  - Expression of cell proliferation and apoptosis biomarkers in pterygia and normal
      conjunctiva.
AB  - PURPOSE: To analyze the expression of apoptosis and cell proliferation molecules
      in pterygium tissues of Chinese patients. METHODS: Thirty-three pterygia were
      surgically removed using the bare sclera procedure, and 23 normal bulbar
      conjunctivas were also obtained. Formalin-fixed, paraffin-wax-embedded tissues
      were analyzed by immunohistochemistry with anti- proliferating cell nuclear
      antigen (PCNA), K(i)-67 (a proliferating cell marker), mutant p53 (mP53), Bcl-2
      associated X-protein (BAX), B-cell lymphoma gene 2 (Bcl-2), and caspase-3
      antibodies. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling assay (TUNEL) analysis was used to analyze the apoptotic cells. RESULTS:
      Our study revealed that the positive rate of PCNA and K(i)-67 significantly
      increased in the pterygium samples compared to the normal conjunctiva samples. In
      the molecules involved in apoptosis, the results showed that the positive rate of
      Bcl-2 and mP53 significantly increased in the pterygium samples. However, no
      difference was found between the pterygium and normal conjunctiva samples in the
      expression of Bax and caspase-3. Through TUNEL analysis, apoptotic cells were
      seen in the entire width of the epithelial layer in normal conjunctivas but were
      found mainly confined to the outer layer of the epithelial cells in pterygia.
      CONCLUSIONS: The finding of high levels of cellular proliferation and low levels
      of cellular apoptosis in pterygia confirmed that both cell apoptosis and
      proliferation are known to play an important role in human pterygium
      pathogenesis.

PMID- 21738399
TI  - Clinicopathological correlation analysis of (lymph) angiogenesis and corneal
      graft rejection.
AB  - PURPOSE: To investigate the relationship of (lymph) angiogenesis and survival
      time of human cornea grafts. METHODS: This was a case series study. A total of
      250 patients requiring a second keratoplasty were screened according to our
      inclusion criteria: 1) only cases with primary non-inflamed cornea diseases were
      included; and 2) all primary diseased cornea specimens from the first corneal
      transplantation were confirmed not to have hemangiogenesis or lymphangiogenesis.
      The included patients were analyzed retrospectively and followed up for the
      survival time of the first and second grafts. Blood vessel content (BVC) and
      lymphatic vessel content (LVC) were assessed in the primary diseased cornea;
      first rejected grafts (including BVC(1) and LVC(1)) and second rejected grafts
      (including BVC(2) and LVC(2)) were assessed by immunohistochemistry. The survival
      times of the first (STG(1)) and second (STG(2)) rejected corneal grafts were
      calculated and the relationship between human corneal (lymph) angiogenesis and
      STG was statistically analyzed. RESULTS: After screening, only 23 patients (23
      eyes) were included. Their primary cornea diseases were non-inflamed, including
      keratoconus (n=14), leukoma (n=5), and Fuchs endothelial dystrophy (n=4). The
      mean duration of follow up was 36 months after the second keratoplasty. In all,
      55 cornea specimens from different times following penetrating keratoplasty were
      collected and examined, including 23 primary non-inflamed corneas (without
      angiogenesis), 23 first rejected corneal grafts (all with hemangiogenesis, but
      only six cases with blown lymphatic vessels), and nine rejected corneal grafts
      (including six cases identified with lymphangiogenesis in the first rejection,
      all with lymphangiogenesis and hemangiogenesis). Based on our statistical
      analysis, STG(1) was correlated with LVC(1) but not with BVC(1) or
      (LVC(1)+BVC(1)), while STG(2) was correlated with (LVC(1)+LVC(2)), LVC(1),
      LVC(2), (LVC(2)+BVC(2)) and (LVC(1)+BVC(1)) but not with BVC(1) or BVC(2).
      CONCLUSIONS: The survival time of human cornea grafts is related to both
      lymphangiogenesis and hemangiogenesis. Lymphangiogenesis only occurred in some
      rejected cases, but it seems to be a signal of poor prognosis for the new
      allograft.

PMID- 21738400
TI  - The expression of retinal cell markers in human retinal pigment epithelial cells
      and their augmentation by the synthetic retinoid fenretinide.
AB  - PURPOSE: In several species the retinal pigment epithelium (RPE) has the
      potential to transdifferentiate into retinal cells to regenerate functional
      retinal tissue after injury. However, this capacity for regeneration is lost in
      mammals. The synthetic retinoic acid derivative, fenretinide [N(4-hydroxyphenyl)
      retinamide], induces a neuronal-like phenotype in the human adult retinal pigment
      epithelial cell line (ARPE-19). These changes are characterized by the appearance
      of neural-like processes and the expression of neuronal markers not normally
      associated with RPE cells. Here we assess whether fenretinide can induce a
      neuroretinal cell phenotype in ARPE-19 cells, by examining retinal cell marker
      expression. METHODS: ARPE-19 cells were treated daily with culture medium
      containing either 3 MUM fenretinide or dimethyl sulfoxide as a control for 7
      days. Cells were processed for immunocytochemistry, western blotting, and for
      analysis by PCR to examine the expression of a panel of RPE, neural, and retinal
      associated cellular markers, including classical and non-canonical opsins.
      RESULTS: Treatment with fenretinide for 7 days induced the formation of neuronal
      like processes in ARPE-19 cells. Fenretinide induced the expression of the cone
      long wavelength sensitive opsin (OPN1lw) but not rhodopsin (RHO), while
      decreasing the expression of RPE cell markers. Many of the neuronal and retinal
      specific markers examined were expressed in both control and fenretinide treated
      cells, including those involved in photoreceptor cell development and the
      multipotency of neural retinal progenitor cells. Interestingly, ARPE-19 cells
      also expressed both photoreceptor specific and non-specific canonical opsins.
      CONCLUSIONS: The expression of retinal-associated markers and loss of RPE cell
      markers in control ARPE-19 cells suggests that these cells might have
      dedifferentiated from an RPE cell phenotype under standard culture conditions.
      The expression of molecules, such as the transcription factors paired box 6 gene
      (PAX6), sex determining region Y-box 2 (SOX2), cone-rod homeobox (CRX), and
      neural retina leucine zipper (NRL), further implies that in culture these cells
      are predisposed toward a retinal progenitor-like state. The fenretinide-induced
      increase in photoreceptor cell markers, accompanied by a decrease in RPE cell
      markers, suggests that retinoids may play a role in the transdifferentiation of
      RPE cells. Importantly, our data show for the first time the expression of a
      vertebrate ciliary opsin (OPN1lw) and rhabdomeric-like opsin, opsin 4 (OPN4 also
      known as melanopsin) in a clonal cell line. Together these data suggest that ARPE
      19 cells are primed for and possess the capacity to differentiate toward a
      retinal cell-like lineage.

PMID- 21738401
TI  - Retinal ganglion cell axonal compression by retinal vessels in light-induced
      retinal degeneration.
AB  - PURPOSE: To analyze the damage produced by light in mydriatic and miotic albino
      retinas under two different sources of light. METHODS: Albino Sprague Dawley
      female rats were exposed to 3,000 lx during 48 h under two different light
      sources: linear and circular bulbs. Before exposure, their left pupils were
      dilated. Before and at different times after light exposure (ALE),
      electroretinographic signals were recorded. One week before processing, retinal
      ganglion cells (RGCs) were traced by applying fluorogold on the superior
      colliculi. Just before processing, some animals were intravenously injected with
      horseradish peroxidase to analyze retinal vascular leakage. At different times
      ALE, animals were sacrificed and their retinas dissected as whole mounts or cross
      sections. Cross-sections were used to study the retinal degeneration and to
      detect apoptotic nuclei by the transferase dUTP nick end labeling (TUNEL)
      technique. Whole mounts were used to analyze vascular leakage; investigate the
      nerve fiber layer, identified by immunodetection of neurofilaments; and quantify
      the whole population of RGCs identified by fluorogold tracing and Brn3a
      immunodetection. With the quantitative data, detailed isodensity maps were
      generated to study the spatial loss of RGCs. RESULTS: Phototoxicity causes an
      immediate and permanent abolishment of the electroretinographic response. Early
      ALE, photoreceptors degenerate by apoptosis and this death is more severe in
      mydriatic conditions and under circular bulbs. Photoreceptor loss starts in an
      arciform dorsomedial retinal area, but at 3 months ALE has spread to the whole
      retina and there are no differences related to either pupil dilation or light
      source. Three months ALE, RGC axons show distorted trajectories and abnormal
      expression of neurofilaments. Six months or more ALE, there is significant death
      of RGCs caused by axonal strangulation by displaced inner retinal vessels.
      Topography of the surviving RGCs shows that their loss is not uniform throughout
      the retina. CONCLUSIONS: Light damage to photoreceptors depends on pupil dilation
      and light source, but affects all retinal layers with time. These deteriorative
      events are also observed in light-induced and inherited retinal degenerations in
      pigmented animals, but occur differently. Thus, the role of ocular pigmentation
      and the etiology of photoreceptor degeneration on retinal remodelling deserve
      further investigation.

PMID- 21738402
TI  - Evaluation of LOXL1 polymorphisms in exfoliation syndrome in the Uygur
      population.
AB  - PURPOSE: In Uygur populations, exfoliation syndrome (XFS) and exfoliation
      glaucoma (XFG) occurred at a high frequency. In this study, we evaluate the
      association profiles of the lysyl oxidase-like 1 (LOXL1) gene polymorphisms with
      XFS in the Uygur population. METHODS: Sixty-four unrelated Uygur patients with
      XFS and 127 Uygur control subjects were included in this study. Genotypes of the
      three single nucleotide polymorphisms (SNPs) of LOXL1 (rs1048661, rs2165241, and
      rs3825942) were analyzed by direct sequencing, and a case-control association
      study was performed. RESULTS: The three SNPs were significantly associated with
      XFS and XFG individually. The G allele of rs1048661 (OR [95%CI]: 1.92 [1.14
      3.22]), G of rs3825942 (OR [95%CI]: 4.86 [2.02-11.68]), and T of rs2165241 (OR
      [95%CI]: 3.98 [2.54-6.25]) were risk alleles for the disorder. The genotypes GG
      for rs1048661 (OR [95%CI]: 2.13 [1.14-3.97]), GG for rs3825942 (OR [95%CI]: 5.68
      [2.28-14.17]), and TT for rs2165241 (OR [95%CI]: 6.13 [2.68-14.01]) were risk
      genotypes for the disease. The haplotypes G-G for the SNPs rs1048661and
      rs3825942, G-T for the SNPs rs1048661 and rs2165241, and SNPs rs3825942 and
      rs2165241 were found to be significantly associated with XFS/G. The haplotypes G
      G-T for the three SNPs were determined to be significantly associated with XFS/G.
      There were significant differences of the allelic and genotypic proportion in
      different gender/age patients and controls for all three SNPs. T allele of
      rs2165241 and G of rs3825942 were risk alleles for the disorder in both the male
      and female groups. G allele of rs1048661 was a risk allele for the disorder in
      the below 65-year-old group. T of rs2165241 was a risk allele for the disorder in
      both age groups. G of rs3825942 was a risk allele for the disorder in the over 65
      year-old group. The genotypes also showed significant differences in the below 65
      year-old group of rs1048661, both groups of rs2165241, and over 65-year-old group
      of rs3825942. CONCLUSIONS: LOXL1 is a susceptibility gene of XFS/XFG in Uygur
      populations. The risk alleles of rs1048661, rs3825942 and rs2165241 in Uygur
      subjects were found to be similar to those of populations in Iceland and the
      United States and different from Han populations in China. The genotypic and
      allelic distributions of these SNPs are similar between XFS and XFG.

PMID- 21738404
TI  - Treatment pulse application for magnetic stimulation.
AB  - Treatment and diagnosis can be made in difficult areas simply by changing the
      output pulse form of the magnetic stimulation device. However, there is a
      limitation in the range of treatments and diagnoses of a conventional sinusoidal
      stimulation treatment pulse because the intensity, width, and form of the pulse
      must be changed according to the lesion type. This paper reports a multidischarge
      method, where the stimulation coils were driven in sequence via multiple
      switching control. The limitation of the existing simple sinusoidal pulse form
      could be overcome by changing the intensity, width, and form of the pulse. In
      this study, a new sequential discharge method was proposed to freely alter the
      pulse width. The output characteristics of the stimulation treatment pulse were
      examined according to the trigger signal delay applied to the switch at each
      stage by applying a range of superposition pulses to the magnetic simulation
      device, which is widely used in industry and medicine.

PMID- 21738403
TI  - Transforming growth factor-beta2 increases extracellular matrix proteins in optic
      nerve head cells via activation of the Smad signaling pathway.
AB  - PURPOSE: Transforming growth factor-beta2 (TGF-beta2) is associated with
      glaucomatous neuropathy, primarily via the increased synthesis and secretion of
      extracellular matrix (ECM) proteins and remodeling of the optic nerve head (ONH).
      Here, we investigated the signaling pathways used by TGF-beta2 to stimulate ECM
      expression by ONH astrocytes and lamina cribrosa (LC) cells. METHODS: TGF-beta2
      localization and secretion was examined in human donor tissues and ONH astrocytes
      and LC cells. To examine TGF-beta2 signaling, ONH astrocytes and LC cells were
      treated with recombinant TGF-beta2, and phosphorylation of Smad and non-Smad
      signaling proteins were examined by western blot analyses and immunostaining.
      RESULTS: TGF-beta2 is significantly increased in the LC region of the ONH in
      glaucomatous eyes compared to age-matched normal eyes (n=4, p<0.0013). ONH
      astrocytes and LC cells secrete TGF-beta2, indicating that these cells may be an
      in vivo source of TGF-beta2 in the human ONH. In addition, treatment of ONH
      astrocytes and LC cells with exogenous TGF-beta2 increased ECM protein synthesis
      and secretion. With respect to TGF-beta2 signaling, recombinant TGF-beta2 induced
      phosphorylation of canonical signaling proteins Smad2/3 but did not alter
      phosphorylation of non-canonical signaling proteins extracellular signal
      regulated kinases (ERK)1/2, p38, and c-Jun N-terminal kinases (JNK)1/2 proteins
      in ONH astrocytes and LC cells. Exogenous TGF-beta2 increased co-localization of
      pSmad2/3 with Co-Smad4 in the nucleus of ONH astrocytes and LC cells further
      indicating activation of the canonical Smad signaling pathway. Furthermore,
      inhibition of TGF-beta I receptor activity by SB431542 or inhibition of Smad3
      phosphorylation by SIS3 blocked TGF-beta2 stimulated ECM expression as well as
      activation of downstream canonical pathway signaling molecules. Knockdown of
      either Smad2 or Smad3 via small interfering RNA (siRNA) reduced TGF-beta2
      stimulated ECM proteins in ONH astrocytes and LC cells. CONCLUSIONS: These
      studies indicate that TGF-beta2 utilizes the canonical Smad signaling pathway to
      stimulate ECM synthesis in human ONH cells. Our studies also indicate that
      pSmad2/3 is required for TGF-beta2 stimulation of ECM remodeling.

PMID- 21738405
TI  - Comparison of cell proliferation, protein, and glucose metabolism in
      musculoskeletal tumors in a PET study.
AB  - 11C-choline and 18F-FAMT are known to correlate with tumor cell proliferation and
      amino acid metabolism. We investigated the ability of 11C-Choline and 18F-FAMT
      PET in diagnosis of musculoskeletal tumors in thirty-six patients in comparison
      of 18F-FDG PET. 11C-Choline and 18F-FDG PET were positive in all the malignant
      tumors (n = 13), whereas 18F-FAMT was positive in 11 tumors. The mean SUVs for
      malignant tumors were significantly higher than those for benign lesions in all
      three tracers imaging. A moderate correlation was found between 11C-Choline and
      18F-FDG (r = 0.540, P < .05), or 18F-FAMT and FDG (r = 0.596, P < .05). The
      diagnostic sensitivity and specificity for malignancy were 91.7% and 71.4%,
      respectively, using 11C-choline with a SUV cut-off of 2.69. The sensitivity and
      specificity of 18F-FAMT for malignancy were 66.7% and 85.7%, respectively, using
      a SUV cut-off of 1.26. For 18F-FDG, using a SUV cut-off of 2.77, the sensitivity
      and specificity were 83.3% and 71.4%, respectively. According to ROC analysis,
      the ROC curves for 11C-Choline, 18F-FAMT, and 18F-FDG were 0.855, 0.734, and
      0.847, respectively. 11C-Choline PET is superior in the visualization of
      musculoskeletal tumors with high contrast imaging, whereas the combination of 18F
      FAMT and 18F-FDG PET provides valuable information for the preoperative planning
      in patients with musculoskeletal tumors.

PMID- 21738406
TI  - Eucamaragnathus desenderi, a new ground beetle species from Africa (Coleoptera,
      Carabidae).
AB  - Eucamaragnathus desenderisp. n., a new ground beetle species of the tribe
      Hiletini, is described from eastern and southern Africa and dedicated to the
      recently deceased Belgian carabidologist Konjev Desender. The new taxon is known
      so far from localities in Zambia (Mukuku, southeast of Mansa) and in South Africa
      (Bothaville, south of Klerksdorp). The new species belongs to the Eucamaragnathus
      castelnaui group and is characterized by shape of pronotum, smooth or sparsely
      punctate pronotal transverse impression, characters of male genitalia and elytral
      striae continued to the apex. Illustrations of the habitus, the median lobe and
      its internal sac and several other morphological features are presented. An
      updated identification key to the African Eucamaragnathus species is given.

PMID- 21738407
TI  - Calleida desenderi, new species from Ecuador (Coleoptera, Carabidae, Lebiinae).
AB  - Calleida desenderi Casale, sp. n., is described from Ecuador, Napo Province,
      surroundings of San Rafael. The new taxon is mostly characterized by the head and
      appendages rufous, the disc of elytra with marked metallic green reflection, the
      median lobe of aedeagus ring-like, and the endophallus with a long, twisted
      flagellum. A key for identification of the closer Neotropical species described
      so far is also provided.

PMID- 21738408
TI  - Forty years of carabid beetle research in Europe - from taxonomy, biology,
      ecology and population studies to bioindication, habitat assessment and
      conservation.
AB  - 'Carabidologists do it all' (Niemela 1996a) is a phrase with which most European
      carabidologists are familiar. Indeed, during the last half a century,
      professional and amateur entomologists have contributed enormously to our
      understanding of the basic biology of carabid beetles. The success of the field
      is in no small part due to regular European Carabidologists' Meetings, which
      started in 1969 in Wijster, the Netherlands, with the 14th meeting again held in
      the Netherlands in 2009, celebrating the 40th anniversary of the first meeting
      and 50 years of long-term research in the Dwingelderveld. This paper offers a
      subjective summary of some of the major developments in carabidology since the
      1960s. Taxonomy of the family Carabidae is now reasonably established, and the
      application of modern taxonomic tools has brought up several surprises like
      elsewhere in the animal kingdom. Progress has been made on the ultimate and
      proximate factors of seasonality and timing of reproduction, which only
      exceptionally show non-seasonality. Triggers can be linked to evolutionary events
      and plausibly explained by the "taxon cycle" theory. Fairly little is still known
      about certain feeding preferences, including granivory and ants, as well as
      unique life history strategies, such as ectoparasitism and predation on higher
      taxa. The study of carabids has been instrumental in developing metapopulation
      theory (even if it was termed differently). Dispersal is one of the areas
      intensively studied, and results show an intricate interaction between walking
      and flying as the major mechanisms. The ecological study of carabids is still
      hampered by some unresolved questions about sampling and data evaluation. It is
      recognised that knowledge is uneven, especially concerning larvae and species in
      tropical areas. By their abundance and wide distribution, carabid beetles can be
      useful in population studies, bioindication, conservation biology and landscape
      ecology. Indeed, 40 years of carabidological research have provided so much data
      and insights, that among insects - and arguably most other terrestrial organisms 
      carabid beetles are one of the most worthwhile model groups for biological
      studies.

PMID- 21738409
TI  - Sub-fossil beetle assemblages associated with the "mammoth fauna" in the Late
      Pleistocene localities of the Ural Mountains and West Siberia.
AB  - The distribution of beetles at the end of the Middle Pleninglacial (=terminal
      Quaternary) was examined based on sub-fossil material from the Ural Mountains and
      Western Siberia, Russia. All relevant localities of fossil insects have similar
      radiocarbon dates, ranging between 33,000 and 22,000 C14 years ago. Being
      situated across the vast territory from the southern Ural Mountains in the South
      to the middle Yamal Peninsula in the North, they allow latitudinal changes in
      beetle assemblages of that time to be traced. These beetles lived simultaneously
      with mammals of the so-called "mammoth fauna" with mammoth, bison, and wooly
      rhinoceros, the often co-occurring mega-mammalian bones at some of the sites
      being evidence of this. The beetle assemblages found between 59 degrees  and 57
      degrees N appear to be the most interesting. Their bulk is referred to as a
      "mixed" type, one which includes a characteristic combination of arcto-boreal,
      boreal, steppe and polyzonal species showing no analogues among recent insect
      complexes. These peculiar faunas seem to have represented a particular zonal
      type, which disappeared since the end of the Last Glaciation to arrive here with
      the extinction of the mammoth biota. In contrast, on the sites lying north of 60
      degrees N, the beetle communities were similar to modern sub-arctic and arctic
      faunas, yet with the participation of some sub-boreal steppe components, such as
      Poecilus ravus Lutshnik and Carabus sibiricus Fischer-Waldheim. This information,
      when compared with our knowledge of synchronous insect faunas from other regions
      of northern Eurasia, suggests that the former distribution of beetles in this
      region could be accounted for both by palaeo-environmental conditions and the
      impact of grazing by large ruminant mammals across the so-called "mammoth
      savannas".

PMID- 21738410
TI  - Predator feeding choice on conspicuous and non-conspicuous carabid beetles: first
      results.
AB  - Insects use various types of behaviour, chemical defences, mimetic, aposematic or
      cryptic appearances as anti-predatory strategies. Among insects, carabid beetles
      of the genus Brachinus are distasteful prey because they discharge an irritating
      "cloud" of quinones when threatened. These beetles live in aggregations and adopt
      warning (conspicuous pattern) colours and chemicals to create a template that is
      easily learnt by predators. Another carabid beetle, Anchomenus dorsalis, mimics
      the colours and cuticular profile of Brachinus and is usually found in Brachinus
      aggregations. In this paper we report results from laboratory observations on
      feeding choice of the following natural predators - Crocidura leucodon
      (Insectivora: Soricidae), Ocypus olens (Coleoptera: Staphylinidae) and Podarcis
      sicula (Reptilia: Lacertidae) - on carabid beetle species. Comparing the number
      of attacks of predators towards aposematic and non-aposematic prey, there was a
      statistically significant preference towards non-aposematic prey.

PMID- 21738411
TI  - Predation of amphibians by carabid beetles of the genus Epomis found in the
      central coastal plain of Israel.
AB  - The genus Epomis is represented in Israel by two species: Epomis dejeani and
      Epomis circumscriptus. In the central coastal plain these species are sympatric
      but do not occur in the same sites. The objective of this study was to record and
      describe trophic interactions between the adult beetles and amphibian species
      occurring in the central coastal plain of Israel. Day and night surveys at three
      sites, as well as controlled laboratory experiments were conducted for studying
      beetle-amphibian trophic interaction. In the field we recorded three cases of
      Epomis dejeani preying upon amphibian metamorphs and also found that Epomis
      adults share shelters with amphibians. Laboratory experiments supported the
      observations that both Epomis species can prey on amphibians. Predation of the
      three anuran species (Bufo viridis, Hyla savignyi and Rana bedriagae) and two
      urodele species (Triturus vittatus and Salamandra salamandra infraimmaculata) is
      described. Only Epomis dejeani consumed Triturus vittatus. Therefore, we conclude
      that the two species display a partial overlap in food habit.

PMID- 21738412
TI  - Current knowledge on exocrine glands in carabid beetles: structure, function and
      chemical compounds.
AB  - Many exocrine products used by ground beetles are pheromones and allomones that
      regulate intra- and interspecific interactions and contribute to their success in
      terrestrial ecosystems. This mini-review attempts to unify major themes related
      to the exocrine glands of carabid beetles. Here we report on both glandular
      structures and the role of secretions in carabid adults, and that little
      information is available on the ecological significance of glandular secretions
      in pre-imaginal stages.

PMID- 21738413
TI  - Morphometry of eyes, antennae and wings in three species of Siagona(Coleoptera,
      Carabidae).
AB  - In carabid beetles, physiological and behavioural characteristics reflect
      specific habitat demands and there is a strong correlation between body form and
      habit in species with different life style. In this study, we compared the
      morphometry and compound eye characteristics of three species of the genus
      Siagona: Siagona jenissoni, Siagona dejeani and Siagona europaea. These carabids
      have a stenotopic lifestyle in Mediterranean clayey soils, inhabiting the ground
      fissure system formed during the dry season. All species have a Mediterranean
      distribution and are nocturnal olfactory hunters, and are strict ant predators.
      For morphometric measurements, we considered body length (mm), wing length (mm),
      antenna length (mm), head width (mm), trochanter length (mm), number of
      ommatidia, eye surface area (mm2), ommatidia density (number of ommatidia/mm2 of
      eye surface area), head height (mm), thorax height (mm) and abdomen height (mm).
      The data revealed intersexual and interspecific differences. The three species
      differ in relative length of the antennae, density and number of ommatidia and
      relative trochanter length. Significant differences occurred in wing sizes, which
      are well developed in Siagona europaea, the only species capable of flight. When
      eye size is compared with other ground beetles of various lifestyles, Siagona
      shows pronounced "microphthalmy" an adaptation to subterranean life in clayey
      crevices of tropical and subtropical climates with a marked dry season.

PMID- 21738414
TI  - Heavy metals in carabids (Coleoptera, Carabidae).
AB  - Carabid beetles (Coleoptera, Carabidae) are one of the most studied soil groups
      in relation to heavy metal (HM) accumulation and use for bioindication of
      environmental pollution. Accumulation of Zn and Cu in carabid beetles was species
      , sex- and trophic group-specific. No differences were found in HM contents
      between omnivorous and carnivorous species. The use of carabid beetles as
      indicators of HM accumulation appears to be rather limited.

PMID- 21738415
TI  - Using demographic data to better interpret pitfall trap catches.
AB  - The results of pitfall trapping are often interpreted as abundance in a
      particular habitat. At the same time, there are numerous cases of almost
      unrealistically high catches of ground beetles in seemingly unsuitable sites. The
      correlation of catches by pitfall trapping with the true distribution and
      abundance of Carabidae needs corroboration. During a full year survey in 2006/07
      in the Lake Elton region (Volgograd Area, Russia), 175 species of ground beetles
      were trapped. Considering the differences in demographic structure of the local
      populations, and not their abundances, three groups of species were recognized:
      residents, migrants and sporadic. In residents, the demographic structure of
      local populations is complete, and their habitats can be considered
      "residential". In migrants and sporadic species, the demographic structure of the
      local populations is incomplete, and their habitats can be considered "transit".
      Residents interact both with their prey and with each other in a particular
      habitat. Sporadic species are hardly important to a carabid community because of
      their low abundances. The contribution of migrants to the structure of carabid
      communities is not apparent and requires additional research. Migrants and
      sporadic species represent a "labile" component in ground beetles communities, as
      opposed to a "stable" component, represented by residents. The variability of the
      labile component substantially limits our interpretation of species diversity in
      carabid communities. Thus, the criteria for determining the most abundant, or
      dominant species inevitably vary because the abundance of migrants in some cases
      can be one order of magnitude higher than that of residents. The results of
      pitfall trapping adequately reflect the state of carabid communities only in
      zonal habitats, while azonal and disturbed habitats are merely transit ones for
      many species of ground beetles. A study of the demographic structure of local
      populations and assessment of the migratory/residential status of particular
      carabid species are potential ways of increasing the reliability of pitfall trap
      information.

PMID- 21738416
TI  - When to sample in an inaccessible landscape: a case study with carabids from the
      Allgau (northern Alps) (Coleoptera, Carabidae).
AB  - While pitfall trapping is generally accepted as the standard method for sampling
      carabid beetles, this method has rarely been used in mountain ecosystems, mainly
      due to the high labour intensity it involves. As part of a research project in
      the German Alps, we investigated the phenologic appearance of adult carabid
      beetles in mountain ecosystems along with the consequences of possible reductions
      in sampling periods. Our results show that an early activity peak among carabids
      is predominant in mountain ecosystems. However, there are differences among
      species: the main group of species showed the highest activity directly after
      snow melt, a second group showed a delayed activity peak and a small third group
      had no clear peak at all. Based on this study, we recommend two fortnightly
      sampling periods as a minimum for a sampling programme: one immediately after
      snow melt, and a second sampling period after a pause of two weeks.

PMID- 21738417
TI  - A plea for using qualitative aspects in the interpretation of ecological field
      data as revealed by the proof of carabid beetle assemblages of a pristine salt
      marsh.
AB  - The evaluation of ecological field data can be done by an increasing number of
      quantitative methods. The application of these methods often is often blind
      against two kinds of problems: (i) the data often do not meet the requirements of
      a method, e.g., as an ultra-metric structure of the data in the case of
      hierarchical cluster analysis. In such cases, the result will be misleading
      because the presentation of results is ultra-metric independent on the structure
      of the data. (ii) Most of the animals are able to move actively or may drift
      passively by wind, etc. Therefore, species occurring by accident like vagrants
      have to be eliminated from the assemblage of animals at a particular site before
      a quantitative method is applied. In addition, the result of a quantitative
      analysis has to be checked for its ecological plausibility. This is a qualitative
      step, which can only be done by taking into account the known data on biology and
      ecology of the species.Some pitfalls of an exclusive application of quantitative
      methods will be demonstrated in this paper using a data set of salt marsh
      Carabidae.

PMID- 21738418
TI  - Useful model organisms, indicators, or both? Ground beetles (Coleoptera,
      Carabidae) reflecting environmental conditions.
AB  - Classic studies have successfully linked single-species abundances, life-history
      traits, assemblage structures and biomass of carabid beetles to past and present,
      human-caused environmental impacts and variation in 'natural' conditions. This
      evidence has led many to suggest carabids to function as 'indicators' - a term
      that bears multiple meanings. Here, a conservation-oriented definition for an
      indicator is used, carabid indicator potential from seven views is evaluated, and
      ways to proceed in indicator research are discussed. (1) Carabid species richness
      poorly indicates the richness and abundance of other taxa, which underlines the
      importance of using multiple taxa in environmental assessments. The ability of
      assemblage indices and specialist or functional-group abundances to reflect rare
      species and habitats should be examined in detail. (2) Experimental evidence
      suggests that carabids may potentially serve as keystone indicators. (3) Carabids
      are sensitive to human-altered abiotic conditions, such as pesticide use in agro
      ecosystems and heavy metal contamination of soils. Carabids might thus reflect
      ecological sustainability and 'ecosystem health'. (4) Carabid assemblages host
      abundant species characteristic of particular habitat types or successional
      stages, which makes them promising dominance indicators. (5) Carabids reflect
      variation in 'natural' conditions, but vegetation and structural features are
      more commonly adopted as condition indicators. Carabids nevertheless provide yet
      another, equally accurate, view on the structure of the environment. (6) Carabids
      may function as early-warning signalers, as suggested by recent studies linking
      climate and carabid distributions. (7) Carabids reflect natural and human-caused
      disturbances and management, but the usefulness of these responses for
      conservation purposes requires further research. In summary, European carabids
      appear useful model organisms and possibly indicators because they are diverse,
      taxonomically and ecologically well-known, efficiently reflect biotic and abiotic
      conditions, are relevant at multiple spatial scales, and are easy to collect in
      sufficiently large numbers to allow statistical analyses. The assumption that
      carabid responses would reflect rare environmental conditions or the responses of
      rare and threatened species - crucial information for conservationists and
      managers - has not yet been critically evaluated. Even if it holds, the
      usefulness will be context dependent: species and their populations vary,
      conditions vary, questions put forward vary, and assessment goals vary.

PMID- 21738419
TI  - Model of succession in degraded areas based on carabid beetles (Coleoptera,
      Carabidae).
AB  - Degraded areas constitute challenging tasks with respect to sustainable
      management of natural resources. Maintaining or even establishing certain
      successional stages seems to be particularly important. This paper presents a
      model of the succession in five different types of degraded areas in Poland based
      on changes in the carabid fauna. Mean Individual Biomass of Carabidae (MIB) was
      used as a numerical measure for the stage of succession. The run of succession
      differed clearly among the different types of degraded areas. Initial conditions
      (origin of soil and origin of vegetation) and landscape related aspects seem to
      be important with respect to these differences. As characteristic phases, a
      'delay phase', an 'increase phase' and a 'stagnation phase' were identified. In
      general, the runs of succession could be described by four different parameters:
      (1) 'Initial degradation level', (2) 'delay', (3) 'increase rate' and (4)
      'recovery level'. Applying the analytic solution of the logistic equation,
      characteristic values for the parameters were identified for each of the five
      area types. The model is of practical use, because it provides a possibility to
      compare the values of the parameters elaborated in different areas, to give hints
      for intervention and to provide prognoses about future succession in the areas.
      Furthermore, it is possible to transfer the model to other indicators of
      succession.

PMID- 21738420
TI  - Poleward range expansion without a southern contraction in the ground beetle
      Agonum viridicupreum (Coleoptera, Carabidae).
AB  - We investigated the extent of poleward shifts in the distribution range of Agonum
      viridicupreum due to climate change in the western Palaearctic. Species' records
      were obtained from extensive literature sources as well as from collections, and
      consistent amateur entomologists' recordings. Within the general geographic range
      of the species, we analyzed in detail two parts of both, the northern and
      southern distribution range boundaries: (1 and 2) north-western Germany (leading
      or high-latitude edge), (3) Israel and (4) southern Italy (rear or low-latitude
      edge). Temporal changes in the occurrence data of the species indicated a
      northward shift of the leading edge of a minimum of 100 km within the last 50 to
      100 years. In contrast, according to the data gathered, the rear edge has not
      changed during the last decades. Further studies are needed in order to fully
      understand the underlying mechanisms of the different behaviour of leading and
      rear range edges of Agonum viridicupreum in the current context of global change.
      Despite our incomplete understanding, chronosequences of the occurrence of the
      given species have the potential to optimize climate niche modelling to predict
      trends in the distribution range in the future.

PMID- 21738421
TI  - Habitat disturbance and hydrological parameters determine the body size and
      reproductive strategy of alluvial ground beetles.
AB  - Environmental variability is the main driver for the variation of biological
      characteristics (life-history traits) of species. Therefore, life-history traits
      are particularly suited to identify mechanistic linkages between environmental
      variability and species occurrence and can help in explaining ecological
      patterns. For ground beetles, few studies directly related species traits to
      environmental variables. This study aims to analyse how life-history traits of
      alluvial ground beetles are controlled by environmental factors. I expected that
      the occurrence of species and the occurrence of specific traits are closely
      related to hydrological and disturbance parameters. Furthermore I expected most
      of the trait-variation to be explained by a combination of environmental
      variables, rather than by their isolated effects. Ground beetles were sampled in
      the year 2005 in floodplain grassland along the Elbe River in Germany. I used
      redundancy analysis to quantify the effects of hydrological, sediment, and
      disturbance related parameters on both species occurrence and species traits. I
      applied variation partitioning to analyse which environmental compartments
      explain most of the trait variation. Species occurrence and trait variation were
      both mainly controlled by hydrological and flood disturbance parameters. I could
      clearly identify reproductive traits and body size as key traits for floodplain
      ground beetles to cope with the environmental variability. Furthermore,
      combinations of hydrological, habitat disturbance, habitat type, and species
      diversity parameters, rather than their isolated effects, explained large parts
      of ground beetle trait variation. Thus, a main conclusion of this study is that
      ground beetle occurrence is mainly determined by complex, multi-scale
      interactions between environmental variability and their life-history traits.

PMID- 21738422
TI  - Ground beetle (Coleoptera, Carabidae) assemblages inhabiting Scots pine stands of
      Puszcza Piska Forest: six-year responses to a tornado impact.
AB  - Ground beetle assemblages were studied during 2003-08 in the Pisz Forest by
      comparing stands disturbed by a tornado to undisturbed control stands. The
      following exploratory questions were put forward. (1) How do the carabid
      assemblages change during six years following the tornado impact? (2) Does the
      carabid assemblage recovery begin during the six first post-tornado years? To
      assess the state of carabid assemblages we used two indices: the MIB (Mean
      Individual Biomass) and the SPC (Sum of Progressive Characteristics). Carabid
      assemblages in the disturbed and in the control stands, as expressed by these two
      indices, were compared using the length of a regression distance (sample distance
      in a MIB:SPC coordinate system). A cluster analysis revealed that the assemblages
      of the disturbed and the control stands were different. The tornado-impacted
      stands produced lower carabid catch rates, but species richness was significantly
      higher there than in the control stands. They hosted lower proportions of
      individuals of European species, of large zoophages, and of forest and
      brachypterous species, than the control stands. The observed reduction in SPC and
      MIB, and an increase in the regression distances may indicate that the carabid
      assemblages had not started to recover from the tornado-caused disturbance.
      Carabid assemblages apparently responded to the tornado in two steps. Firstly,
      the first three years were characterized by moderate decreases of index values.
      Secondly, from the fourth to the sixth year after the tornado, many observed
      changes became magnified. We did not observe clear signals of the recovery of
      forest carabid assemblages during the six follow-up years.

PMID- 21738423
TI  - Carabid beetle diversity and mean individual biomass in beech forests of various
      ages.
AB  - Carabid beetle diversity and mean individual biomass (MIB) were analysed in three
      different successional stages of beech tree stands (60, 80 and 150 years old).
      Carabid beetles were captured using pitfall traps placed at nine sites (three per
      age class) in the Papuk Mountain of East Croatia during 2008. A cluster analysis
      identified three groupings that corresponded to the beech age classes. MIB values
      increased with stand age, ranging from 255 in 60-year-old stand to 537 in the
      oldest forests. The 80-year-old stand showed the highest species richness and
      diversity values. With respect to species composition, large species such as
      Carabus scheidleri and Carabus coriaceus were dominant only in the oldest
      forests. Furthermore, species that overwinter in the larval stage were more
      abundant in the oldest forests (45% of the total number of individuals from the
      150-year-old stand) than in the younger ones (20% of individuals from 60-year
      old, and 22% of individuals from 80-year-old stands). Our results showed that the
      analyses of species composition and life history traits are valuable for
      estimating the conservation values of older forests. Although the investigated
      sites form part of a continuous forested area and are only a couple of kilometres
      apart, MIB values detect significant differences associated with forest age and
      can be a useful tool in evaluating the degree to which a forest reflects a
      natural state.

PMID- 21738424
TI  - Changes in salt-marsh carabid assemblages after an invasion by the native grass
      Elymus athericus (Link) Kerguelen.
AB  - As a result of an invasion by the native grass Elymus athericus (Link) Kerguelen
      (Poaceae) in the last 10 years, a major change in vegetation cover has occurred
      in salt marshes of the Mont Saint-Michel bay, Western France. The impact of such
      an invasion on carabid assemblages, a dominant group of terrestrial arthropods in
      these habitats and containing several stenotopic species, is investigated here.
      In our study site, carabid data are available from 1983 and 1984, allowing a
      comparison of species distribution ranges in salt marshes before (1983-1984) and
      after (2002) the Elymus athericus invasion. A total of 16,867 adults belonging to
      40 species were caught. By considering the presence-absence of species shared
      between studies, we show that the invasion by Elymus athericus promoted the
      progression of non-coastal species (mainly Pterostichus s.l. spp.). This did
      however not interfere with resident species distributions, finally resulting in
      higher carabid species richness in the entire area. The species composition and
      abundances of carabid assemblages were also compared between natural and invaded
      stations in 2002. The main result is that abundances of some halophilic species
      decreased in one invaded plot (in case of Pogonus chalceus (Marsham 1802))
      whereas the opposite pattern was observed for other species (e.g., Bembidion
      minimum (Fabricius 1792)). Invaded habitats were characterized by lower
      percentages of halophilic species and higher total species richness.

PMID- 21738425
TI  - Effects of ecological flooding on the temporal and spatial dynamics of carabid
      beetles (Coleoptera, Carabidae) and springtails (Collembola) in a polder habitat.
AB  - Within the scope of the Integrated Rhine Program an ecological flood gate and
      channel was inserted into the polder "Ingelheim" to enhance animal and plant
      diversity. In 2008, carabid beetles and springtails were collected, using pitfall
      traps, to measure the effects of ecological flooding and a strong precipitation
      event at a flood-disturbed and a dry location in this area. At both localities,
      xerophilic and mesophilic carabid beetle species were dominant throughout the
      study period. The total number of individuals of hygrophilic species was
      comparatively constant, while species number increased, partly due to the changed
      moisture conditions caused by ecological flooding and strong precipitation.
      Carabid beetle diversity and evenness decreased marginally when ecological
      flooding was absent. Springtails represent a less mobile arthropod order, and as
      such the impact of ecological flooding was stronger. An increase in both numbers
      of species and individuals of hygrophilic and hygrotolerant species occurred in
      the flood-disturbed location after ecological flooding. After the sites at both
      locations had dried, the number of individuals belonging to these species
      declined rapidly. In contrast to carabid species, the strong precipitation event
      showed no influence on hygrophilic springtail species. Thus, collembolan
      diversity and evenness decreased markedly in the absence of flooding. We showed
      that ecological flooding has an influence on the spatial and temporal dynamics of
      different arthropod groups that inhabit the polder "Ingelheim". These findings
      demonstrate the importance of using different arthropod groups as bioindicators
      in determining the ecological value of a particular polder design.

PMID- 21738426
TI  - Assemblages of carabid beetles (Coleoptera, Carabidae) in humid forest habitats
      of different stages of succession in the Puszcza Knyszynska Forest (northeastern
      Poland).
AB  - During a period of three years (2006-2008) the carabid fauna in wet and humid
      forest habitats of different stages of succession was studied at the Puszcza
      Knyszynska (north-east part of Poland). The aim of this study was to determine
      how the assemblages of the carabid fauna change in relation to the ongoing
      process of succession. Using pitfall traps, 24 plots were sampled. The plots were
      located in stands of different age, from two year old plantations to more than
      100 year old forests. Additionally, the stands were ordered in three moisture
      classes (wet, humid and very humid) and two classes of soil richness. As
      indicators for change in the carabid fauna in relation to age of the stands Mean
      Individual Biomass (MIB), species diversity and share of forest species were
      used. By applying multivariate statistics the relation of the different habitat
      characteristics to changes in the carabid fauna was examined. During the study
      8903 individuals belonging to 57 species were collected. Pterostichus niger
      represented 28% of the total catches and therefore the most common species.
      Another common species, Pterostichus melanarius, contributed to 13% of the total
      catch. This species was caught at every plot, even in the old forests. In
      contrast to the results obtained by Szyszko (1990) for fresh and dry pine stands,
      in this study the relation of MIB with the age of forest was not significant.
      Although the number of species was rather constant, the number of individuals
      belonging to the group of forest species significantly increased with the ageing
      of the forest. The multivariate analysis showed a relationship with ageing of the
      stands and soil richness rather than with moisture and size of the forest.
      According to the present paper, clear cuttings in wet and humid habitats do not
      cause a strong degradation of the carabid fauna.

PMID- 21738427
TI  - Belowground carabid beetle diversity in the western Palaearctic - effects of
      history and climate on range-restricted taxa (Coleoptera, Carabidae).
AB  - Broad-scale patterns of subterranean diversity are a fascinating but neglected
      part of biodiversity research. Carabid beetles adapted to belowground habitats
      form a particularly species-rich part of the subterranean fauna. We studied large
      scale diversity patterns of these belowground carabids across the western
      Palaearctic and evaluated potential impacts of historical and contemporary
      environmental conditions on the distribution of these taxa, using available
      species richness and environmental data at country level. Regression modelling
      and variation partitioning showed a strong relationship between species richness
      and range in elevation. Potential effects of climatic variables, mainly those
      related to ambient energy input, were much weaker. We discuss the implications of
      this combination of effects, which suggests, concordant with the absence of
      subterranean carabids in northern and highest richness in southern Europe, a
      strong prevailing influence of historical processes on current richness
      distributions of these taxa. Previous studies did not provide clear indications
      for such an influence. In contrast to more mobile and widespread carabid beetles,
      dispersal limitation due to high adaptation of belowground carabids to
      subterranean habitats has probably hindered their re-colonization of former
      permafrost and glaciated regions. Hotspots of highest belowground diversity are
      located in regions with an assumed long-term stability of environmental
      conditions, correlating with patterns of other dispersal-limited taxa such as
      many endemic plants. Our study provides important new information in the
      discussion of potential determinants of the distinct geographic patterns of
      belowground diversity. Moreover, it contributes to a better understanding of
      range size related differences previously found in the distribution of diversity
      and environmental dependencies of widespread and range-restricted species within
      the highly diverse carabid beetles.

PMID- 21738428
TI  - Recent records of steppe species in Belarus, first indications of a steppe
      species invasion?
AB  - BELARUS IS SITUATED AT A CROSSROAD OF NATURAL BORDERS OF SPECIES DISTRIBUTIONS:
      the NE part is situated in a taiga zone, whereas the other part of terrain is in
      the European forest zone. The distance of Belarus to the steppe zone is about 330
      kilometers. This geographical position and the extensive knowledge of its fauna
      can be used to monitor changes in the distribution of different species. An
      intensive study of open habitat ground beetles was carried out from 1975-2008 in
      Belarus, using pitfall traps, quadrate-sampling methods, hand collecting, netting
      and light traps. In total, more than 130 000 specimens of ground beetles
      belonging to 169 species were collected from 62 fields and 11 meadows of
      different types. 217 specimens of Calosoma investigator (Illiger 1798), 2
      specimens of Calosoma denticolle (Gebler 1833), and one specimen of Harpalus
      subcylindricus (Dejean, 1829), Harpalus honestus (Duftschmid 1812) and Zabrus
      tenebrioides (Goeze 1777) were present in this material. All specimens were
      macropterous and exclusively caught at fields and waste grounds on sandy soil.
      Nowadays Belarus is the northernmost location for these species in Eastern
      Europe. Steppe species most probably migrated to SE Belarus from NE Ukraine,
      using Dnieper and its river valleys. The shift in the geographic distribution of
      steppe species during the last thirty years in Belarus have been attributed to a
      higher frequency of warmer and wetter summers in the last few decades.

PMID- 21738429
TI  - How unique is the tiger beetle fauna (Coleoptera, Cicindelidae) of the Balkan
      Peninsula?
AB  - The tiger beetle fauna of the Balkan Peninsula is one of the richest in Europe
      and includes 19 species or 41% of the European tiger beetle fauna. Assembled by
      their biogeographical origins, the Balkan tiger beetle species fall into 14
      different groups that include, Mediterranean, Middle Oriental, Central Asiatic,
      Euro-Siberian, South and East European, Pannonian-Sarmatian, West Palaearctic,
      Turano-European and Afrotropico Indo-Mediterranean species. The Mediterranean
      Sclerophyl and the Pontian Steppe are the Balkan biogeographical provinces with
      the highest species richness, while the Balkan Highlands has the lowest
      Cicindelidae diversity. Most species are restricted to single habitat types in
      lowland areas of the Balkan Peninsula and only Calomera aulica aulica and
      Calomera littoralis nemoralis occur in respectively 3 and 4 different types of
      habitat. About 60% of all Balkan Cicindelidae species are found in habitats
      potentially endangered by human activity.

PMID- 21738430
TI  - Ground beetles of the Ukraine (Coleoptera, Carabidae).
AB  - A review of the ground beetles of the Ukrainian fauna is given. Almost 750
      species from 117 genera of Carabidae are known to occur in the Ukraine.
      Approximately 450 species of ground beetles are registered in the Carpathian
      region. No less than 300 species of ground beetles are found in the forest zone.
      Approximately 400 species of Carabidae present in the forest-steppe zone are
      relatively similar in species composition to those in the forest territories.
      Some 450 species of Carabidae are inhabitants of the steppe zone. Representatives
      of many other regions of heterogeneous biotopes such as forest, semi desert,
      intrazonal, etc. can be found in the steppe areas. The fauna of Carabidae (ca.
      100 species) of the lowlands of southern Ukraine (sandy biotopes), situated
      mostly in the Kherson region, is very peculiar. The fauna of the Crimean
      mountains contains about 300 species. Conservation measures for the Carabidae are
      discussed.

PMID- 21738431
TI  - What do we know about winter active ground beetles (Coleoptera, Carabidae) in
      Central and Northern Europe?
AB  - This paper summarizes the current knowledge on winter active Carabidae in Central
      and Northern Europe. In total 73 winter active species are listed, based on
      literature and own observations. Ground beetles are among the three most numerous
      Coleoptera families active during the autumn to spring period. The winter
      community of Carabidae is composed both of larvae (mainly autumn breeding
      species) and adults, as well as of epigeic species and those inhabiting tree
      trunks. Supranivean fauna is characterized by lower species diversity than the
      subnivean fauna. The activity of ground beetles decreases in late autumn, is
      lowest during mid-winter and increases in early spring. Carabidae are noted as an
      important food source in the diet of insectivorous mammals. They are also
      predators, hunting small winter active invertebrates.

PMID- 21738432
TI  - Calodromius bifasciatus and other Carabidae on 26 oak-trunks in a nature reserve
      in the Netherlands.
AB  - The discovery of Calodromius bifasciatus in the nature reserve 'De Kaaistoep',
      the Netherlands, initiated research on this and related carabid beetles between
      2000 and 2006. During this period we investigated the trunks of 26 Pedunculate
      oaks, mainly during nightly observations, to learn more about arboricolous
      carabid species. We observed more than 3000 specimens of 24 carabid species. The
      majority of these species were Dromiuss.l., however Calodromius bifasciatus
      dominated the dataset. Our data on phenology clearly show that Calodromius
      bifasciatus is mainly active in winter; it even copulates just above freezing
      point. Other interesting observations were made as well; for instance the
      presence of a small sphere at the end of the abdomen and their hiding behaviour
      at low temperatures. Subsequently, we obtained similar information about other
      tree dwelling carabid species. In this article we present an overview of all
      species observed on the trunks, after which we shall focus on the observations
      made on Calodromius bifasciatus.

PMID- 21738433
TI  - Historical ecology meets conservation and evolutionary genetics: a secondary
      contact zone between Carabus violaceus (Coleoptera, Carabidae) populations
      inhabiting ancient and recent woodlands in north-western Germany.
AB  - Only very few cases have documented that an increase in connectivity after a
      period of fragmentation in ecological time has had an effect on the distribution,
      genetic structure and morphology of stenotopic species. In this study we present
      an example of clinal variability in a woodland ground beetle as a result of
      changes in the connectivity of a landscape during the last two centuries. The
      study area hosts both the nominate form Carabus violaceus s. str. and the
      subspecies Carabus violaceus purpurascens, which is ranked as a distinct species
      by some authors. We studied 12 Carabus violaceus populations from a 30 km
      transect of ancient and recent forests in north-western Germany. We analyzed
      three polymorphic enzyme loci, classified the elytron sculpture and measured the
      shape of the aedeagus tip of the specimens. Carabus violaceus showed secondary
      gradients both in allozyme markers and morphometric characters in our study area.
      A genetic differentiation of 16% between the populations is high but lies within
      the range of intraspecific variability in habitat specialists of the genus
      Carabus. Populations had no significant deficit of heterozygotes. We found many
      hybrid populations in terms of morphological properties. This study highlights
      the conservation value of ancient woodland and the consequences of landscape
      connectivity and defragmentation on the genetic setting of a ground beetle.
      Moreover, it shows that differences in the external shape of male genitalia do
      not prevent gene flow within the genus Carabus. Thus, the establishment of
      species status should not exclusively be based on this property.

PMID- 21738434
TI  - Animals as an indicator of carbon sequestration and valuable landscapes.
AB  - Possibilities of the assessment of a landscape with the use of succession
      development stages, monitored with the value of the Mean Individual Biomass (MIB)
      of carabid beetles and the occurrence of bird species are discussed on the basis
      of an example from Poland. Higher variability of the MIB value in space signifies
      a greater biodiversity. Apart from the variability of MIB, it is suggested to
      adopt the occurrence of the following animals as indicators, (in the order of
      importance), representing underlying valuable landscapes: black stork, lesser
      spotted eagle, white-tailed eagle, wolf, crane and white stork. The higher number
      of these species and their greater density indicate a higher value of the
      landscape for biodiversity and ecosystem services, especially carbon
      sequestration. All these indicators may be useful to assess measures for
      sustainable land use.

PMID- 21738435
TI  - The spider family Selenopidae (Arachnida, Araneae) in Australasia and the
      Oriental Region.
AB  - We relimit and revise the family Selenopidae to include four new genera and 27
      new species from Australia and the Oriental Region. The family is redefined, as
      are the genera Anyphops Benoit, Garcorops Corronca, Hovops Benoit, Selenops
      Latreille, and Siamspinops Dankittipakul & Corronca, to accommodate the new
      genera and to correct previous inconsistencies in the diagnoses and definitions
      of the aforementioned genera. The species of Selenops that occur throughout India
      and China are also reviewed. Three species occur in China: Selenops bursarius
      Karsch 1879, also known from Japan, Korea and Taiwan, Selenops ollarius Zhu, Sha,
      & Chen 1990, and Selenops radiatus Latreille 1819, the type of the genus and most
      widespread selenopid. Selenops cordatus Zhu, Sha & Chen syn. n. is recognized as
      a junior synonym of Selenops radiatus. Amamanganopsgen. n. is monotypic, with
      Amamanganops baginawasp. n. (?; from the Philippines). Godumopsgen. n. is
      monotypic, with Godumops caritussp. n. (?; from Papua New Guinea). Karaopsgen. n.
      occurs throughout Australia and includes 24 species. A new combination is
      proposed for Karaops australiensis (L. Koch 1875) comb. n. (ex. Selenops), and
      the new species: Karaops gangariesp. n. (?, ?), Karaops monteithisp. n. (?),
      Karaops alanlongbottomisp. n. (?), Karaops keithlongbottomisp. n. (?), Karaops
      larryoosp. n. (?), Karaops jarritsp. n. (?,?), Karaops marrayagongsp. n. (?),
      Karaops ravenisp. n. (?,?), Karaops badgeraddasp. n. (?), Karaops burbidgeisp. n.
      (?,?), Karaops karrawarlasp. n. (?,?), Karaops julianneaesp. n. (?), Karaops
      martamartasp. n. (?), Karaops manaaynsp. n. (?, ?), Karaops vadlaadambarasp. n.
      (?, ?), Karaops pilkingtonisp. n. (?, ?), Karaops deserticolasp. n. (?), Karaops
      ngarutjaranyasp. n. (?,?), Karaops francesaesp. n. (?,?), Karaops toolbrunupsp.
      n. (?, ?), the type species Karaops ellenaesp. n. (?,?), Karaops jenniferaesp. n.
      (?), and Karaops dawarasp. n. (?).The genus Makdiopsgen. n. contains five species
      from India and Nepal. A new combination is proposed for Makdiops agumbensis
      (Tikader 1969), comb. n., Makdiops montigenus (Simon 1889), comb. n., Makdiops
      nilgirensis (Reimoser 1934) comb. n.,(ex. Selenops). Also, there are two new
      species the type of the genus Makdiops mahishasurasp. n. (?; from India), and
      Makdiops shivasp. n. (?). The genus Pakawopsgen. n. is monotypic. A new
      combination is proposed for Pakawops formosanus (Kayashima 1943) comb. n. (ex.
      Selenops), known only from Taiwan. A new combination is proposed for Siamspinops
      aculeatus (Simon)comb. n. (ex. Selenops). The distribution and diversity of the
      studied selenopid fauna is discussed. Finally, keys are provided to all of the
      selenopid genera and to the species of Karaopsgen. n.and Makdiopsgen. n.

PMID- 21738436
TI  - Improved Protein-A separation of V(H)3 Fab from Fc after papain digestion of
      antibodies.
AB  - Antibody-binding fragments (Fab) are generated from whole antibodies by treatment
      with papain and can be separated from the Fc component using Protein-A affinity
      chromatography. Commercial kits are available, which facilitate the production
      and purification of Fab fragments; however, the manufacturer fails to report that
      this method is inefficient for antibodies with V(H)3 domains as a result of the
      intrinsic variable region affinity for Protein-A. A commercially available,
      modified Protein-A resin (MabSelect SuRe) has been engineered for greater
      stability. Here, we report that an additional consequence of the modified resin
      is the ability to purify V(H)3 family Fab fragments, which cannot be separated
      effectively from other components of the papain digest by traditional Protein-A
      resin. This improvement of a commonly used procedure is of significance, as
      increasingly, therapeutic antibodies are being derived from human origin, where
      V(H)3 is the most abundantly used variable region family.

PMID- 21738437
TI  - Analysis of the DNA sequencing quality and efficiency of the Apollo100 robotic
      microcycler in a core facility setting.
AB  - Sanger, or dideoxynucleotide sequencing, is an important tool for biomolecular
      research. An important trend in DNA sequencing is to find new and innovative ways
      to provide high-quality, reliable sequences in a more efficient manner, using
      automated capillary electrophoresis. The Apollo100 combines Sanger cycle
      sequencing and solid-phase reversible immobilization for product purification in
      a single instrument with robotic liquid handling and microfluidic (Microscale On
      chip Valve) chips that have onboard thermal cycling and pneumatic mixing.
      Experiments were performed to determine how the DNA sequencing results from the
      Apollo100 compared with conventional, manual methods used in a core facility
      setting. Through rigorous experimentation of multiple baseline runs and a
      dilution series of template concentration, the Apollo100 generated sequencing
      that exceeded 900 bases with a quality score of 20 or above. When comparing
      actual client samples of amplicons, plasmids, and cosmids, Apollo100 sequencing
      results did not differ significantly from those reactions prepared manually. In
      addition, bacterial genomic DNA was sequenced successfully, directly with the
      Apollo100, although results were of lower quality than the standard manual
      method. As a result of the microscale capabilities, the Apollo100 offers valuable
      savings with respect to the quantity of reagents consumed compared with current
      manual sequencing methods, thereby continuing the demand for smaller template and
      reagent requirements. In conclusion, the Apollo100 can generate high-quality DNA
      sequences for common templates equivalent to those produced using manual
      sequencing methods and increases efficiency through reduced labor and reagents.

PMID- 21738438
TI  - Biomolecular and structural analyses of cauliflower-like DNAs by ultraviolet,
      circular dichroism, and fluorescence spectroscopies in comparison with natural
      DNA.
AB  - Cauliflower-like DNAs are stem-loop DNAs that are fabricated periodically in
      inverted repetitions from deoxyribonucleic acid phosphates (dNTPs) by loop
      mediated isothermal amplification (LAMP). Cauliflower-like DNAs have ladder-shape
      behaviors on gel electrophoresis, and increasing the time of LAMP leads to
      multiplying the repetitions, stem-loops, and electrophoretic bands. Cauliflower
      like DNAs were fabricated via LAMP using two loop primers, two bumper primers,
      dNTPs, a lambda-phage DNA template, and a Bst DNA polymerase in 75- and 90-min
      periods. These times led to manufacturing two types of cauliflower-like DNAs with
      different contents of inverted repetitions and stem-loops, which were clearly
      indicated by two comparable electrophoresis patterns in agarose gel. LAMP
      fabricated DNAs and natural dsB-DNA (salmon genomic DNA) were dialyzed in Gomori
      phosphate buffer (10 mM, pH 7.4) to be isolated from salts, nucleotides, and
      primers. Dialyzed DNAs were studied using UV spectroscopy, circular dichroism
      spectropolarimetry, and fluorescence spectrophotometry. Structural analyses
      indicated reduction of the molecular ellipticity and extinction coefficients in
      comparison with B-DNA. Also, cauliflower-like DNAs demonstrated less intrinsic
      and more extrinsic fluorescence in comparison with natural DNA. The overwinding
      and lengthening of the cauliflower-like configurations of LAMP DNAs led to
      changes in physical parameters of this type of DNA in comparison with natural
      DNA. The results obtained introduced new biomolecular characteristics of DNA
      macromolecules fabricated within a LAMP process and show the effects of more
      inverted repeats and stem-loops, which are manufactured by lengthening the
      process.

PMID- 21738439
TI  - Depletion of plasma albumin for proteomic analysis of Bothrops jararaca snake
      plasma.
AB  - The proteomic analysis of plasma samples represents a challenge as a result of
      the presence of highly abundant proteins such as albumin. To enable the detection
      of biomarkers, which are commonly low-abundance proteins, in complex blood
      fluids, it is necessary to remove high-abundance proteins efficiently. Moreover,
      there is a range of about 10 orders of magnitude for the abundance of different
      protein species in serum. Here, we describe for the first time a study of
      reptilian albumin depletion using resins usually used in mammalian plasma
      depletion procedures. We performed the depletion of albumin from Bothrops jaraca
      plasma using the HiTrap Blue high-performance column (GE Healthcare Life
      Sciences, Piscataway, NJ, USA) and the kit Albumin & IgG Depletion SpinTrap
      column (GE Healthcare Life Sciences). In addition, proteomic approaches were used
      to analyze reptilian plasma. Our results showed that B. jararaca albumin bound to
      both columns, but those interactions were not enough to remove a large amount of
      albumin to reach an enrichment of low-abundance proteins. Although the depletion
      techniques used in this work were not the best to remove B. jararaca plasma
      albumin, our present work highlights the similarity between B. jararaca and
      mammalian albumin, contributing to the knowledge of comparative hemostatic
      proteins.

PMID- 21738440
TI  - Variant identification in multi-sample pools by illumina genome analyzer
      sequencing.
AB  - Multi-sample pooling and Illumina Genome Analyzer (GA) sequencing allows high
      throughput sequencing of multiple samples to determine population sequence
      variation. A preliminary experiment, using the RET proto-oncogene as a model,
      predicted <= 30 samples could be pooled to reliably detect singleton variants
      without requiring additional confirmation testing. This report used 30 and 50
      sample pools to test the hypothesized pooling limit and also to test recent
      protocol improvements, Illumina GAIIx upgrades, and longer read chemistry. The
      SequalPrep(TM) method was used to normalize amplicons before pooling. For
      comparison, a single 'control' sample was run in a different flow cell lane. Data
      was evaluated by variant read percentages and the subtractive correction method
      which utilizes the control sample. In total, 59 variants were detected within the
      pooled samples, which included all 47 known true variants. The 15 known singleton
      variants due to Sanger sequencing had an average of 1.62 +/- 0.26% variant reads
      for the 30 pool (expected 1.67% for a singleton variant [unique variant within
      the pool]) and 1.01 +/- 0.19% for the 50 pool (expected 1%). The 76 base read
      lengths had higher error rates than shorter read lengths (33 and 50 base reads),
      which eliminated the distinction of true singleton variants from background
      error. This report demonstrated pooling limits from 30 up to 50 samples
      (depending on error rates and coverage), for reliable singleton variant
      detection. The presented pooling protocols and analysis methods can be used for
      variant discovery in other genes, facilitating molecular diagnostic test design
      and interpretation.

PMID- 21738443
TI  - Library Outreach to Support Groups: A Case Study.
AB  - Information sharing is a key component of patient and caregiver support groups.
      Hospital libraries that provide consumer health and patient information services
      can increase their visibility among support groups through presentations,
      facilitator training, brochures and other media. This case study details a
      project at a regional medical center in Virginia to provide outreach to groups
      that met regularly at the hospital or nearby facilities. Initial evaluation
      suggests that group members who attended librarian presentations are likely to
      use the health sciences library and MedlinePlus in the future.

PMID- 21738444
TI  - Substantial histone reduction modulates genomewide nucleosomal occupancy and
      global transcriptional output.
AB  - The basic unit of genome packaging is the nucleosome, and nucleosomes have long
      been proposed to restrict DNA accessibility both to damage and to transcription.
      Nucleosome number in cells was considered fixed, but recently aging yeast and
      mammalian cells were shown to contain fewer nucleosomes. We show here that
      mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a
      reduced amount of core, linker, and variant histones, and a correspondingly
      reduced number of nucleosomes, possibly because HMGB1 facilitates nucleosome
      assembly. Yeast nhp6 mutants lacking Nhp6a and -b proteins, which are related to
      HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome
      limitation in both mammalian and yeast cells increases the sensitivity of DNA to
      damage, increases transcription globally, and affects the relative expression of
      about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in
      four does not affect the location of nucleosomes and their spacing, but
      nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform and
      can be modelled assuming that different nucleosomal sites compete for available
      histones. Sites with a high propensity to occupation are almost always packaged
      into nucleosomes both in wild type and nucleosome-depleted cells; nucleosomes on
      sites with low propensity to occupation are disproportionately lost in nucleosome
      depleted cells. We suggest that variation in nucleosome number, by affecting
      nucleosomal occupancy both genomewide and gene-specifically, constitutes a novel
      layer of epigenetic regulation.

PMID- 21738445
TI  - Learning: not just the facts, ma'am, but the counterfactuals as well.

PMID- 21738446
TI  - Counterfactual choice and learning in a neural network centered on human lateral
      frontopolar cortex.
AB  - Decision making and learning in a real-world context require organisms to track
      not only the choices they make and the outcomes that follow but also other
      untaken, or counterfactual, choices and their outcomes. Although the neural
      system responsible for tracking the value of choices actually taken is
      increasingly well understood, whether a neural system tracks counterfactual
      information is currently unclear. Using a three-alternative decision-making task,
      a Bayesian reinforcement-learning algorithm, and fMRI, we investigated the coding
      of counterfactual choices and prediction errors in the human brain. Rather than
      representing evidence favoring multiple counterfactual choices, lateral frontal
      polar cortex (lFPC), dorsomedial frontal cortex (DMFC), and posteromedial cortex
      (PMC) encode the reward-based evidence favoring the best counterfactual option at
      future decisions. In addition to encoding counterfactual reward expectations, the
      network carries a signal for learning about counterfactual options when feedback
      is available-a counterfactual prediction error. Unlike other brain regions that
      have been associated with the processing of counterfactual outcomes,
      counterfactual prediction errors within the identified network cannot be related
      to regret theory. Furthermore, individual variation in counterfactual choice
      related activity and prediction error-related activity, respectively, predicts
      variation in the propensity to switch to profitable choices in the future and the
      ability to learn from hypothetical feedback. Taken together, these data provide
      both neural and behavioral evidence to support the existence of a previously
      unidentified neural system responsible for tracking both counterfactual choice
      options and their outcomes.

PMID- 21738447
TI  - Not all genes are equal; shortage of histones affects some genes more than
      others.

PMID- 21738448
TI  - The dynamics of health and return migration.
AB  - The increasing importance and complexity of migration globally also implies a
      global increase in return migration, and thus an increased interest in the health
      of returning migrants. The health of returning migrants is impacted by the
      cumulative exposure to social determinants and risk factors of health during the
      migration process, during the return movement, and following return. Circular
      migration often occurs among the diaspora, which can result in the transfer of
      knowledge and skills that contribute to development, including health system
      strengthening. Migrants with dual nationality often return to countries with
      better health services than their country of origin when they are sick and can
      not get care at home. To maintain and improve the health of returning migrants,
      multi-sectoral policies at global and national levels should facilitate access to
      appropriate and equitable health services, social services, and continuity of
      care across and within borders.

PMID- 21738449
TI  - Cardiac complications in patients with community-acquired pneumonia: a systematic
      review and meta-analysis of observational studies.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity
      and mortality. CAP can trigger acute cardiac events. We sought to determine the
      incidence of major cardiac complications in CAP patients to characterize the
      magnitude of this problem. METHODS AND FINDINGS: Two investigators searched
      MEDLINE, Scopus, and EMBASE for observational studies of immunocompetent adults
      with clinical and radiological evidence of CAP that reported any of the
      following: overall cardiac complications, incident heart failure, acute coronary
      syndromes (ACS), or incident cardiac arrhythmias occurring within 30 days of CAP
      diagnosis. At a minimum, studies had to establish enrolment procedures and
      inclusion and exclusion criteria, enroll their patients sequentially, and report
      the incidence of cardiac complications as a function of their entire cohorts.
      Studies with focus on nosocomial or health care-associated pneumonia were not
      included. Review of 2,176 citations yielded 25 articles that met eligibility and
      minimum quality criteria. Seventeen articles (68%) reported cohorts of CAP
      inpatients. In this group, the pooled incidence rates for overall cardiac
      complications (six cohorts, 2,119 patients), incident heart failure (eight
      cohorts, 4,215 patients), acute coronary syndromes (six cohorts, 2,657 patients),
      and incident cardiac arrhythmias (six cohorts, 2,596 patients), were 17.7%
      (confidence interval [CI] 13.9-22.2), 14.1% (9.3-20.6), 5.3% (3.2-8.6), and 4.7%
      (2.4-8.9), respectively. One article reported cardiac complications in CAP
      outpatients, four in low-risk (not severely ill) inpatients, and three in high
      risk inpatients. The incidences for all outcomes except overall cardiac
      complications were lower in the two former groups and higher in the latter. One
      additional study reported on CAP outpatients and low-risk inpatients without
      discriminating between these groups. Twelve studies (48%) asserted the evaluation
      of cardiac complications in their methods but only six (24%) provided a
      definition for them. Only three studies, all examining ACS, carried out risk
      factor analysis for these events. No study analyzed the association between
      cardiac complications and other medical complications or their impact on other
      CAP outcomes. CONCLUSIONS: Major cardiac complications occur in a substantial
      proportion of patients with CAP. Physicians and patients need to appreciate the
      significance of this association for timely recognition and management of these
      events. Strategies aimed at preventing pneumonia (i.e., influenza and
      pneumococcal vaccination) in high-risk populations need to be optimized. Further
      research is needed to understand the mechanisms underlying this association,
      measure the impact of cardiac complications on other CAP outcomes, identify those
      patients with CAP at high risk of developing cardiac complications, and design
      strategies to prevent their occurrence in this population.

PMID- 21738450
TI  - Scaling up global health interventions: a proposed framework for success.
AB  - Drawing upon interviews with experts and a review of the literature, Gavin Yamey
      proposes a new framework for scaling up global health interventions.

PMID- 21738451
TI  - Energy density, portion size, and eating occasions: contributions to increased
      energy intake in the United States, 1977-2006.
AB  - BACKGROUND: Competing theories attempt to explain changes in total energy (TE)
      intake; however, a rigorous, comprehensive examination of these explanations has
      not been undertaken. Our objective was to examine the relative contribution of
      energy density (ED), portion size (PS), and the number of eating/drinking
      occasions (EOs) to changes in daily TE. METHODS AND FINDINGS: Using cross
      sectional nationally representative data from the Nationwide Food Consumption
      Survey (1977-78), Continuing Survey of Food Intakes of Individuals (1989-91), and
      National Health and Nutrition Examination Surveys (1994-98 and 2003-06) for
      adults (aged >=19 y), we mathematically decompose TE (kcal/d) to understand the
      relative contributions of each component-PS (grams/EO), ED (kcal/g/EO) and
      EO(number)-to changes in TE over time. There was an increase in TE intake (+570
      kcal/d) and the number of daily EOs (+1.1) between 1977-78 and 2003-06. The
      average PS increased between 1977-78 and 1994-98, then dropped slightly between
      1994-98 and 2003-06, while the average ED remained steady between 1977-78 and
      1989-91, then declined slightly between 1989-91 and 1994-98. Estimates from the
      decomposition statistical models suggest that between 1977-78 and 1989-91,
      annualized changes in PS contributed nearly 15 kcal/d/y to increases in TE, while
      changes in EO accounted for just 4 kcal/d/y. Between 1994-98 and 2003-06 changes
      in EO accounted for 39 kcal/d/y of increase and changes in PS accounted for 1
      kcal/d/y of decline in the annualized change in TE. CONCLUSIONS: While all three
      components have contributed to some extent to 30-y changes in TE, changes in EO
      and PS have accounted for most of the change. These findings suggest a new focus
      for efforts to reduce energy imbalances in US adults.

PMID- 21738452
TI  - The effect of handwashing at recommended times with water alone and with soap on
      child diarrhea in rural Bangladesh: an observational study.
AB  - BACKGROUND: Standard public health interventions to improve hand hygiene in
      communities with high levels of child mortality encourage community residents to
      wash their hands with soap at five separate key times, a recommendation that
      would require mothers living in impoverished households to typically wash hands
      with soap more than ten times per day. We analyzed data from households that
      received no intervention in a large prospective project evaluation to assess the
      relationship between observed handwashing behavior and subsequent diarrhea.
      METHODS AND FINDINGS: Fieldworkers conducted a 5-hour structured observation and
      a cross-sectional survey in 347 households from 50 villages across rural
      Bangladesh in 2007. For the subsequent 2 years, a trained community resident
      visited each of the enrolled households every month and collected information on
      the occurrence of diarrhea in the preceding 48 hours among household residents
      under the age of 5 years. Compared with children living in households where
      persons prepared food without washing their hands, children living in households
      where the food preparer washed at least one hand with water only (odds ratio
      [OR]=0.78; 95% confidence interval [CI]=0.57-1.05), washed both hands with water
      only (OR=0.67; 95% CI=0.51-0.89), or washed at least one hand with soap (OR=0.30;
      95% CI=0.19-0.47) had less diarrhea. In households where residents washed at
      least one hand with soap after defecation, children had less diarrhea (OR=0.45;
      95% CI=0.26-0.77). There was no significant association between handwashing with
      or without soap before feeding a child, before eating, or after cleaning a
      child's anus who defecated and subsequent child diarrhea. CONCLUSIONS: These
      observations suggest that handwashing before preparing food is a particularly
      important opportunity to prevent childhood diarrhea, and that handwashing with
      water alone can significantly reduce childhood diarrhea.

PMID- 21738453
TI  - Activated membrane patches guide chemotactic cell motility.
AB  - Many eukaryotic cells are able to crawl on surfaces and guide their motility
      based on environmental cues. These cues are interpreted by signaling systems
      which couple to cell mechanics; indeed membrane protrusions in crawling cells are
      often accompanied by activated membrane patches, which are localized areas of
      increased concentration of one or more signaling components. To determine how
      these patches are related to cell motion, we examine the spatial localization of
      RasGTP in chemotaxing Dictyostelium discoideum cells under conditions where the
      vertical extent of the cell was restricted. Quantitative analyses of the data
      reveal a high degree of spatial correlation between patches of activated Ras and
      membrane protrusions. Based on these findings, we formulate a model for amoeboid
      cell motion that consists of two coupled modules. The first module utilizes a
      recently developed two-component reaction diffusion model that generates
      transient and localized areas of elevated concentration of one of the components
      along the membrane. The activated patches determine the location of membrane
      protrusions (and overall cell motion) that are computed in the second module,
      which also takes into account the cortical tension and the availability of
      protrusion resources. We show that our model is able to produce realistic
      amoeboid-like motion and that our numerical results are consistent with
      experimentally observed pseudopod dynamics. Specifically, we show that the
      commonly observed splitting of pseudopods can result directly from the dynamics
      of the signaling patches.

PMID- 21738454
TI  - Differential producibility analysis (DPA) of transcriptomic data with metabolic
      networks: deconstructing the metabolic response of M. tuberculosis.
AB  - A general paucity of knowledge about the metabolic state of Mycobacterium
      tuberculosis within the host environment is a major factor impeding development
      of novel drugs against tuberculosis. Current experimental methods do not allow
      direct determination of the global metabolic state of a bacterial pathogen in
      vivo, but the transcriptional activity of all encoded genes has been investigated
      in numerous microarray studies. We describe a novel algorithm, Differential
      Producibility Analysis (DPA) that uses a metabolic network to extract metabolic
      signals from transcriptome data. The method utilizes Flux Balance Analysis (FBA)
      to identify the set of genes that affect the ability to produce each metabolite
      in the network. Subsequently, Rank Product Analysis is used to identify those
      metabolites predicted to be most affected by a transcriptional signal. We first
      apply DPA to investigate the metabolic response of E. coli to both anaerobic
      growth and inactivation of the FNR global regulator. DPA successfully extracts
      metabolic signals that correspond to experimental data and provides novel
      metabolic insights. We next apply DPA to investigate the metabolic response of M.
      tuberculosis to the macrophage environment, human sputum and a range of in vitro
      environmental perturbations. The analysis revealed a previously unrecognized
      feature of the response of M. tuberculosis to the macrophage environment: a down
      regulation of genes influencing metabolites in central metabolism and concomitant
      up-regulation of genes that influence synthesis of cell wall components and
      virulence factors. DPA suggests that a significant feature of the response of the
      tubercle bacillus to the intracellular environment is a channeling of resources
      towards remodeling of its cell envelope, possibly in preparation for attack by
      host defenses. DPA may be used to unravel the mechanisms of virulence and
      persistence of M. tuberculosis and other pathogens and may have general
      application for extracting metabolic signals from other "-omics" data.

PMID- 21738455
TI  - Learning, memory, and the role of neural network architecture.
AB  - The performance of information processing systems, from artificial neural
      networks to natural neuronal ensembles, depends heavily on the underlying system
      architecture. In this study, we compare the performance of parallel and layered
      network architectures during sequential tasks that require both acquisition and
      retention of information, thereby identifying tradeoffs between learning and
      memory processes. During the task of supervised, sequential function
      approximation, networks produce and adapt representations of external
      information. Performance is evaluated by statistically analyzing the error in
      these representations while varying the initial network state, the structure of
      the external information, and the time given to learn the information. We link
      performance to complexity in network architecture by characterizing local error
      landscape curvature. We find that variations in error landscape structure give
      rise to tradeoffs in performance; these include the ability of the network to
      maximize accuracy versus minimize inaccuracy and produce specific versus
      generalizable representations of information. Parallel networks generate smooth
      error landscapes with deep, narrow minima, enabling them to find highly specific
      representations given sufficient time. While accurate, however, these
      representations are difficult to generalize. In contrast, layered networks
      generate rough error landscapes with a variety of local minima, allowing them to
      quickly find coarse representations. Although less accurate, these
      representations are easily adaptable. The presence of measurable performance
      tradeoffs in both layered and parallel networks has implications for
      understanding the behavior of a wide variety of natural and artificial learning
      systems.

PMID- 21738456
TI  - Eurekometrics: analyzing the nature of discovery.

PMID- 21738457
TI  - How haptic size sensations improve distance perception.
AB  - Determining distances to objects is one of the most ubiquitous perceptual tasks
      in everyday life. Nevertheless, it is challenging because the information from a
      single image confounds object size and distance. Though our brains frequently
      judge distances accurately, the underlying computations employed by the brain are
      not well understood. Our work illuminates these computions by formulating a
      family of probabilistic models that encompass a variety of distinct hypotheses
      about distance and size perception. We compare these models' predictions to a set
      of human distance judgments in an interception experiment and use Bayesian
      analysis tools to quantitatively select the best hypothesis on the basis of its
      explanatory power and robustness over experimental data. The central question is:
      whether, and how, human distance perception incorporates size cues to improve
      accuracy. Our conclusions are: 1) humans incorporate haptic object size
      sensations for distance perception, 2) the incorporation of haptic sensations is
      suboptimal given their reliability, 3) humans use environmentally accurate size
      and distance priors, 4) distance judgments are produced by perceptual "posterior
      sampling". In addition, we compared our model's estimated sensory and motor noise
      parameters with previously reported measurements in the perceptual literature and
      found good correspondence between them. Taken together, these results represent a
      major step forward in establishing the computational underpinnings of human
      distance perception and the role of size information.

PMID- 21738458
TI  - Colocalization of protein kinase A with adenylyl cyclase enhances protein kinase
      A activity during induction of long-lasting long-term-potentiation.
AB  - The ability of neurons to differentially respond to specific temporal and spatial
      input patterns underlies information storage in neural circuits. One means of
      achieving spatial specificity is to restrict signaling molecules to particular
      subcellular compartments using anchoring molecules such as A-Kinase Anchoring
      Proteins (AKAPs). Disruption of protein kinase A (PKA) anchoring to AKAPs impairs
      a PKA-dependent form of long term potentiation (LTP) in the hippocampus. To
      investigate the role of localized PKA signaling in LTP, we developed a stochastic
      reaction-diffusion model of the signaling pathways leading to PKA activation in
      CA1 pyramidal neurons. Simulations investigated whether the role of anchoring is
      to locate kinases near molecules that activate them, or near their target
      molecules. The results show that anchoring PKA with adenylyl cyclase (which
      produces cAMP that activates PKA) produces significantly greater PKA activity,
      and phosphorylation of both inhibitor-1 and AMPA receptor GluR1 subunit on S845,
      than when PKA is anchored apart from adenylyl cyclase. The spatial microdomain of
      cAMP was smaller than that of PKA suggesting that anchoring PKA near its source
      of cAMP is critical because inactivation by phosphodiesterase limits diffusion of
      cAMP. The prediction that the role of anchoring is to colocalize PKA near
      adenylyl cyclase was confirmed by experimentally rescuing the deficit in LTP
      produced by disruption of PKA anchoring using phosphodiesterase inhibitors.
      Additional experiments confirm the model prediction that disruption of anchoring
      impairs S845 phosphorylation produced by forskolin-induced synaptic potentiation.
      Collectively, these results show that locating PKA near adenylyl cyclase is a
      critical function of anchoring.

PMID- 21738459
TI  - Trade-off between responsiveness and noise suppression in biomolecular system
      responses to environmental cues.
AB  - When living systems detect changes in their external environment their response
      must be measured to balance the need to react appropriately with the need to
      remain stable, ignoring insignificant signals. Because this is a fundamental
      challenge of all biological systems that execute programs in response to stimuli,
      we developed a generalized time-frequency analysis (TFA) framework to
      systematically explore the dynamical properties of biomolecular networks. Using
      TFA, we focused on two well-characterized yeast gene regulatory networks
      responsive to carbon-source shifts and a mammalian innate immune regulatory
      network responsive to lipopolysaccharides (LPS). The networks are comprised of
      two different basic architectures. Dual positive and negative feedback loops make
      up the yeast galactose network; whereas overlapping positive and negative feed
      forward loops are common to the yeast fatty-acid response network and the LPS
      induced network of macrophages. TFA revealed remarkably distinct network
      behaviors in terms of trade-offs in responsiveness and noise suppression that are
      appropriately tuned to each biological response. The wild type galactose network
      was found to be highly responsive while the oleate network has greater noise
      suppression ability. The LPS network appeared more balanced, exhibiting less bias
      toward noise suppression or responsiveness. Exploration of the network parameter
      space exposed dramatic differences in system behaviors for each network. These
      studies highlight fundamental structural and dynamical principles that underlie
      each network, reveal constrained parameters of positive and negative feedback and
      feed-forward strengths that tune the networks appropriately for their respective
      biological roles, and demonstrate the general utility of the TFA approach for
      systems and synthetic biology.

PMID- 21738460
TI  - Spatio-temporal credit assignment in neuronal population learning.
AB  - In learning from trial and error, animals need to relate behavioral decisions to
      environmental reinforcement even though it may be difficult to assign credit to a
      particular decision when outcomes are uncertain or subject to delays. When
      considering the biophysical basis of learning, the credit-assignment problem is
      compounded because the behavioral decisions themselves result from the spatio
      temporal aggregation of many synaptic releases. We present a model of plasticity
      induction for reinforcement learning in a population of leaky integrate and fire
      neurons which is based on a cascade of synaptic memory traces. Each synaptic
      cascade correlates presynaptic input first with postsynaptic events, next with
      the behavioral decisions and finally with external reinforcement. For operant
      conditioning, learning succeeds even when reinforcement is delivered with a delay
      so large that temporal contiguity between decision and pertinent reward is lost
      due to intervening decisions which are themselves subject to delayed
      reinforcement. This shows that the model provides a viable mechanism for temporal
      credit assignment. Further, learning speeds up with increasing population size,
      so the plasticity cascade simultaneously addresses the spatial problem of
      assigning credit to synapses in different population neurons. Simulations on
      other tasks, such as sequential decision making, serve to contrast the
      performance of the proposed scheme to that of temporal difference-based learning.
      We argue that, due to their comparative robustness, synaptic plasticity cascades
      are attractive basic models of reinforcement learning in the brain.

PMID- 21738461
TI  - Network clustering revealed the systemic alterations of mitochondrial protein
      expression.
AB  - The mitochondrial protein repertoire varies depending on the cellular state.
      Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are
      related to a wide range of human diseases; however, little is known about how
      nuclear-encoded mitochondrial proteins (mt proteome) changes under such
      dysfunctional states. In this study, we investigated the systemic alterations of
      mtDNA-depleted (rho(0)) mitochondria by using network analysis of gene expression
      data. By modularizing the quantified proteomics data into protein functional
      networks, systemic properties of mitochondrial dysfunction were analyzed. We
      discovered that up-regulated and down-regulated proteins were organized into two
      predominant subnetworks that exhibited distinct biological processes. The down
      regulated network modules are involved in typical mitochondrial functions, while
      up-regulated proteins are responsible for mtDNA repair and regulation of mt
      protein expression and transport. Furthermore, comparisons of proteome and
      transcriptome data revealed that rho(0) cells attempted to compensate for mtDNA
      depletion by modulating the coordinated expression/transport of mt proteins. Our
      results demonstrate that mt protein composition changed to remodel the functional
      organization of mitochondrial protein networks in response to dysfunctional
      cellular states. Human mt protein functional networks provide a framework for
      understanding how cells respond to mitochondrial dysfunctions.

PMID- 21738462
TI  - Partially glycosylated dendrimers block MD-2 and prevent TLR4-MD-2-LPS complex
      mediated cytokine responses.
AB  - The crystal structure of the TLR4-MD-2-LPS complex responsible for triggering
      powerful pro-inflammatory cytokine responses has recently become available.
      Central to cell surface complex formation is binding of lipopolysaccharide (LPS)
      to soluble MD-2. We have previously shown, in biologically based experiments,
      that a generation 3.5 PAMAM dendrimer with 64 peripheral carboxylic acid groups
      acts as an antagonist of pro-inflammatory cytokine production after surface
      modification with 8 glucosamine molecules. We have also shown using molecular
      modelling approaches that this partially glycosylated dendrimer has the
      flexibility, cluster density, surface electrostatic charge, and hydrophilicity to
      make it a therapeutically useful antagonist of complex formation. These studies
      enabled the computational study of the interactions of the unmodified dendrimer,
      glucosamine, and of the partially glycosylated dendrimer with TLR4 and MD-2 using
      molecular docking and molecular dynamics techniques. They demonstrate that
      dendrimer glucosamine forms co-operative electrostatic interactions with residues
      lining the entrance to MD-2's hydrophobic pocket. Crucially, dendrimer
      glucosamine interferes with the electrostatic binding of: (i) the 4'phosphate on
      the di-glucosamine of LPS to Ser118 on MD-2; (ii) LPS to Lys91 on MD-2; (iii) the
      subsequent binding of TLR4 to Tyr102 on MD-2. This is followed by additional co
      operative interactions between several of the dendrimer glucosamine's carboxylic
      acid branches and MD-2. Collectively, these interactions block the entry of the
      lipid chains of LPS into MD-2's hydrophobic pocket, and also prevent TLR4-MD-2
      LPS complex formation. Our studies have therefore defined the first nonlipid
      based synthetic MD-2 antagonist using both animal model-based studies of pro
      inflammatory cytokine responses and molecular modelling studies of a whole
      dendrimer with its target protein. Using this approach, it should now be possible
      to computationally design additional macromolecular dendrimer based antagonists
      for other Toll Like Receptors. They could be useful for treating a spectrum of
      infectious, inflammatory and malignant diseases.

PMID- 21738463
TI  - Heterogeneous host susceptibility enhances prevalence of mixed-genotype micro
      parasite infections.
AB  - Dose response in micro-parasite infections is usually shallower than predicted by
      the independent action model, which assumes that each infectious unit has a
      probability of infection that is independent of the presence of other infectious
      units. Moreover, the prevalence of mixed-genotype infections was greater than
      predicted by this model. No probabilistic infection model has been proposed to
      account for the higher prevalence of mixed-genotype infections. We use model
      selection within a set of four alternative models to explain high prevalence of
      mixed-genotype infections in combination with a shallow dose response. These
      models contrast dependent versus independent action of micro-parasite infectious
      units, and homogeneous versus heterogeneous host susceptibility. We specifically
      consider a situation in which genome differences between genotypes are minimal,
      and highly unlikely to result in genotype-genotype interactions. Data on dose
      response and mixed-genotype infection prevalence were collected by challenging
      fifth instar Spodoptera exigua larvae with two genotypes of Autographa
      californica multicapsid nucleopolyhedrovirus (AcMNPV), differing only in a 100 bp
      PCR marker sequence. We show that an independent action model that includes
      heterogeneity in host susceptibility can explain both the shallow dose response
      and the high prevalence of mixed-genotype infections. Theoretical results
      indicate that variation in host susceptibility is inextricably linked to
      increased prevalence of mixed-genotype infections. We have shown, to our
      knowledge for the first time, how heterogeneity in host susceptibility affects
      mixed-genotype infection prevalence. No evidence was found that virions operate
      dependently. While it has been recognized that heterogeneity in host
      susceptibility must be included in models of micro-parasite transmission and
      epidemiology to account for dose response, here we show that heterogeneity in
      susceptibility is also a fundamental principle explaining patterns of pathogen
      genetic diversity among hosts in a population. This principle has potentially
      wide implications for the monitoring, modeling and management of infectious
      diseases.

PMID- 21738464
TI  - Computational investigation of the changing patterns of subtype specific NMDA
      receptor activation during physiological glutamatergic neurotransmission.
AB  - NMDA receptors (NMDARs) are the major mediator of the postsynaptic response
      during synaptic neurotransmission. The diversity of roles for NMDARs in
      influencing synaptic plasticity and neuronal survival is often linked to
      selective activation of multiple NMDAR subtypes (NR1/NR2A-NMDARs, NR1/NR2B
      NMDARs, and triheteromeric NR1/NR2A/NR2B-NMDARs). However, the lack of available
      pharmacological tools to block specific NMDAR populations leads to debates on the
      potential role for each NMDAR subtype in physiological signaling, including
      different models of synaptic plasticity. Here, we developed a computational model
      of glutamatergic signaling at a prototypical dendritic spine to examine the
      patterns of NMDAR subtype activation at temporal and spatial resolutions that are
      difficult to obtain experimentally. We demonstrate that NMDAR subtypes have
      different dynamic ranges of activation, with NR1/NR2A-NMDAR activation sensitive
      at univesicular glutamate release conditions, and NR2B containing NMDARs
      contributing at conditions of multivesicular release. We further show that
      NR1/NR2A-NMDAR signaling dominates in conditions simulating long-term depression
      (LTD), while the contribution of NR2B containing NMDAR significantly increases
      for stimulation frequencies that approximate long-term potentiation (LTP).
      Finally, we show that NR1/NR2A-NMDAR content significantly enhances response
      magnitude and fidelity at single synapses during chemical LTP and spike timed
      dependent plasticity induction, pointing out an important developmental switch in
      synaptic maturation. Together, our model suggests that NMDAR subtypes are
      differentially activated during different types of physiological glutamatergic
      signaling, enhancing the ability for individual spines to produce unique
      responses to these different inputs.

PMID- 21738465
TI  - Ten simple rules for building and maintaining a scientific reputation.

PMID- 21738466
TI  - A role for TLR4 in Clostridium difficile infection and the recognition of surface
      layer proteins.
AB  - Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea
      (AAD) and pseudomembranous colitis in humans. The role of the surface layer
      proteins (SLPs) in this disease has not yet been fully explored. The aim of this
      study was to investigate a role for SLPs in the recognition of C. difficile and
      the subsequent activation of the immune system. Bone marrow derived dendritic
      cells (DCs) exposed to SLPs were assessed for production of inflammatory
      cytokines, expression of cell surface markers and their ability to generate T
      helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used
      in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in
      infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs
      characterised by production of IL-12, TNFalpha and IL-10 and expression of MHC
      class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells
      producing IFNgamma and IL-17. SLPs were unable to activate DCs isolated from TLR4
      mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4-/-
      and Myd88-/-, but not TRIF-/- mice were more susceptible than wild-type mice to
      C. difficile infection. Furthermore, SLPs activated NFkappaB, but not IRF3,
      downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can
      activate innate and adaptive immunity and that these effects are mediated by
      TLR4, with TLR4 having a functional role in experimental C. difficile infection.
      This suggests an important role for SLPs in the recognition of C. difficile by
      the immune system.

PMID- 21738467
TI  - T. brucei infection reduces B lymphopoiesis in bone marrow and truncates
      compensatory splenic lymphopoiesis through transitional B-cell apoptosis.
AB  - African trypanosomes of the Trypanosoma brucei species are extracellular
      protozoan parasites that cause the deadly disease African trypanosomiasis in
      humans and contribute to the animal counterpart, Nagana. Trypanosome clearance
      from the bloodstream is mediated by antibodies specific for their Variant Surface
      Glycoprotein (VSG) coat antigens. However, T. brucei infection induces polyclonal
      B cell activation, B cell clonal exhaustion, sustained depletion of mature
      splenic Marginal Zone B (MZB) and Follicular B (FoB) cells, and destruction of
      the B-cell memory compartment. To determine how trypanosome infection compromises
      the humoral immune defense system we used a C57BL/6 T. brucei AnTat 1.1 mouse
      model and multicolor flow cytometry to document B cell development and maturation
      during infection. Our results show a more than 95% reduction in B cell precursor
      numbers from the CLP, pre-pro-B, pro-B, pre-B and immature B cell stages in the
      bone marrow. In the spleen, T. brucei induces extramedullary B lymphopoiesis as
      evidenced by significant increases in HSC-LMPP, CLP, pre-pro-B, pro-B and pre-B
      cell populations. However, final B cell maturation is abrogated by infection
      induced apoptosis of transitional B cells of both the T1 and T2 populations which
      is not uniquely dependent on TNF-, Fas-, or prostaglandin-dependent death
      pathways. Results obtained from ex vivo co-cultures of living bloodstream form
      trypanosomes and splenocytes demonstrate that trypanosome surface coat-dependent
      contact with T1/2 B cells triggers their deletion. We conclude that infection
      induced and possibly parasite-contact dependent deletion of transitional B cells
      prevents replenishment of mature B cell compartments during infection thus
      contributing to a loss of the host's capacity to sustain antibody responses
      against recurring parasitemic waves.

PMID- 21738468
TI  - Impact of endofungal bacteria on infection biology, food safety, and drug
      development.

PMID- 21738469
TI  - HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that
      recruits T cells and fuels conjugate formation with Langerhans cells.
AB  - Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an
      HIV-1 entry portal during sexual transmission. We recently reported that
      efficient HIV-1 transmission occurs following 1 h of polarized exposure of the
      inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free
      virus. At this early time point, Langerhans cells (LCs) and T-cells within the
      inner foreskin epidermis are the first cells targeted by the virus. To gain in
      depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry,
      foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The
      chemokine/cytokine milieu secreted by the foreskin tissue, and resulting
      modifications in density and spatial distribution of T-cells and LCs, were then
      investigated. Our studies show that in the inner foreskin, inoculation with HIV-1
      infected cells induces increased CCL5/RANTES (1.63-fold) and decreased CCL20/MIP
      3-alpha (0.62-fold) secretion. Elevated CCL5/RANTES mediates recruitment of T
      cells from the dermis into the epidermis, which is blocked by a neutralizing
      CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic
      modification in the spatial distribution of epidermal LCs: attraction to the
      apical surface at 1 h, followed by migration back towards the basement membrane
      later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time
      point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates,
      permitting the transfer of HIV-1 captured by LCs. Together, these results reveal
      that HIV-1 induces a dynamic process of immune cells relocation in the inner
      foreskin that is associated with specific chemokines secretion, which favors
      efficient HIV-1 entry at this site.

PMID- 21738470
TI  - The binding of triclosan to SmeT, the repressor of the multidrug efflux pump
      SmeDEF, induces antibiotic resistance in Stenotrophomonas maltophilia.
AB  - The wide utilization of biocides poses a concern on the impact of these compounds
      on natural bacterial populations. Furthermore, it has been demonstrated that
      biocides can select, at least in laboratory experiments, antibiotic resistant
      bacteria. This situation has raised concerns, not just on scientists and
      clinicians, but also on regulatory agencies, which are demanding studies on the
      impact that the utilization of biocides may have on the development on resistance
      and consequently on the treatment of infectious diseases and on human health. In
      the present article, we explored the possibility that the widely used biocide
      triclosan might induce antibiotic resistance using as a model the opportunistic
      pathogen Stenotrophomonas maltophilia. Biochemical, functional and structural
      studies were performed, focusing on SmeDEF, the most relevant antibiotic- and
      triclosan-removing multidrug efflux pump of S. maltophilia. Expression of smeDEF
      is regulated by the repressor SmeT. Triclosan released SmeT from its operator and
      induces the expression of smeDEF, thus reducing the susceptibility of S.
      maltophilia to antibiotics in the presence of the biocide. The structure of SmeT
      bound to triclosan is described. Two molecules of triclosan were found to bind to
      one subunit of the SmeT homodimer. The binding of the biocide stabilizes the N
      terminal domain of both subunits in a conformation unable to bind DNA. To our
      knowledge this is the first crystal structure obtained for a transcriptional
      regulator bound to triclosan. This work provides the molecular basis for
      understanding the mechanisms allowing the induction of phenotypic resistance to
      antibiotics by triclosan.

PMID- 21738471
TI  - Tipping the balance: Sclerotinia sclerotiorum secreted oxalic acid suppresses
      host defenses by manipulating the host redox environment.
AB  - Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely
      broad host range. This pathogen produces the non-specific phytotoxin and key
      pathogenicity factor, oxalic acid (OA). Our recent work indicated that this
      fungus and more specifically OA, can induce apoptotic-like programmed cell death
      (PCD) in plant hosts, this induction of PCD and disease requires generation of
      reactive oxygen species (ROS) in the host, a process triggered by fungal secreted
      OA. Conversely, during the initial stages of infection, OA also dampens the plant
      oxidative burst, an early host response generally associated with plant defense.
      This scenario presents a challenge regarding the mechanistic details of OA
      function; as OA both suppresses and induces host ROS during the compatible
      interaction. In the present study we generated transgenic plants expressing a
      redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA)
      generates a reducing environment in host cells that suppress host defense
      responses including the oxidative burst and callose deposition, akin to
      compatible biotrophic pathogens. Once infection is established however, this
      necrotroph induces the generation of plant ROS leading to PCD of host tissue, the
      result of which is of direct benefit to the pathogen. In contrast, a non
      pathogenic OA-deficient mutant failed to alter host redox status. The mutant
      produced hypersensitive response-like features following host inoculation,
      including ROS induction, callose formation, restricted growth and cell death.
      These results indicate active recognition of the mutant and further point to
      suppression of defenses by the wild type necrotrophic fungus. Chemical reduction
      of host cells with dithiothreitol (DTT) or potassium oxalate (KOA) restored the
      ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy
      involving regulation of host redox status to establish infection. These results
      address a long-standing issue involving the ability of OA to both inhibit and
      promote ROS to achieve pathogenic success.

PMID- 21738472
TI  - HSV-2 infection of dendritic cells amplifies a highly susceptible HIV-1 cell
      target.
AB  - Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and,
      although several reports describe the interaction between these two viruses, the
      exact mechanism for this increased susceptibility remains unclear. Dendritic
      cells (DCs) at the site of entry of HSV-2 and HIV-1 contribute to viral spread in
      the mucosa. Specialized DCs present in the gut-associated lymphoid tissues
      produce retinoic acid (RA), an important immunomodulator, able to influence HIV-1
      replication and a key mediator of integrin alpha4beta7 on lymphocytes.
      alpha4beta7 can be engaged by HIV-1 on the cell-surface and CD4+ T cells
      expressing high levels of this integrin (alpha4beta7 (high)) are particularly
      susceptible to HIV-1 infection. Herein we provide in-vivo data in macaques
      showing an increased percentage of alpha4beta7 (high) CD4+ T cells in rectal
      mucosa, iliac lymph nodes and blood within 6 days of rectal exposure to live (n =
      11), but not UV-treated (n = 8), HSV-2. We found that CD11c+ DCs are a major
      target of HSV-2 infection in in-vitro exposed PBMCs. We determined that immature
      monocyte-derived DCs (moDCs) express aldehyde dehydrogenase ALDH1A1, an enzyme
      essential for RA production, which increases upon HSV-2 infection. Moreover, HSV
      2-infected moDCs significantly increase alpha4beta7 expression on CD4+ T
      lymphocytes and HIV-1 infection in DC-T cell mixtures in a RA-dependent manner.
      Thus, we propose that HSV-2 modulates its microenviroment, influencing DC
      function, increasing RA production capability and amplifying a alpha4beta7
      (high)CD4+ T cells. These factors may play a role in increasing the
      susceptibility to HIV-1.

PMID- 21738473
TI  - A dynamic landscape for antibody binding modulates antibody-mediated
      neutralization of West Nile virus.
AB  - Neutralizing antibodies are a significant component of the host's protective
      response against flavivirus infection. Neutralization of flaviviruses occurs when
      individual virions are engaged by antibodies with a stoichiometry that exceeds a
      required threshold. From this "multiple-hit" perspective, the neutralizing
      activity of antibodies is governed by the affinity with which it binds its
      epitope and the number of times this determinant is displayed on the surface of
      the virion. In this study, we investigated time-dependent changes in the fate of
      West Nile virus (WNV) decorated with antibody in solution. Experiments with the
      well-characterized neutralizing monoclonal antibody (MAb) E16 revealed a
      significant increase in neutralization activity over time that could not be
      explained by the kinetics of antibody binding, virion aggregation, or the action
      of complement. Additional kinetic experiments using the fusion-loop specific MAb
      E53, which has limited neutralizing activity because it recognizes a relatively
      inaccessible epitope on mature virions, identified a role of virus "breathing" in
      regulating neutralization activity. Remarkably, MAb E53 neutralized mature WNV in
      a time- and temperature-dependent manner. This phenomenon was confirmed in
      studies with a large panel of MAbs specific for epitopes in each domain of the
      WNV envelope protein, with sera from recipients of a live attenuated WNV vaccine,
      and in experiments with dengue virus. Given enough time, significant inhibition
      of infection was observed even for antibodies with very limited, or no
      neutralizing activity in standard neutralization assays. Together, our data
      suggests that the structural dynamics of flaviviruses impacts antibody-mediated
      neutralization via exposure of otherwise inaccessible epitopes, allowing for
      antibodies to dock on the virion with a stoichiometry sufficient for
      neutralization.

PMID- 21738474
TI  - The SV40 late protein VP4 is a viroporin that forms pores to disrupt membranes
      for viral release.
AB  - Nonenveloped viruses are generally released by the timely lysis of the host cell
      by a poorly understood process. For the nonenveloped virus SV40, virions assemble
      in the nucleus and then must be released from the host cell without being
      encapsulated by cellular membranes. This process appears to involve the well
      controlled insertion of viral proteins into host cellular membranes rendering
      them permeable to large molecules. VP4 is a newly identified SV40 gene product
      that is expressed at late times during the viral life cycle that corresponds to
      the time of cell lysis. To investigate the role of this late expressed protein in
      viral release, water-soluble VP4 was expressed and purified as a GST fusion
      protein from bacteria. Purified VP4 was found to efficiently bind biological
      membranes and support their disruption. VP4 perforated membranes by directly
      interacting with the membrane bilayer as demonstrated by flotation assays and the
      release of fluorescent markers encapsulated into large unilamellar vesicles or
      liposomes. The central hydrophobic domain of VP4 was essential for membrane
      binding and disruption. VP4 displayed a preference for membranes comprised of
      lipids that replicated the composition of the plasma membranes over that of
      nuclear membranes. Phosphatidylethanolamine, a lipid found at high levels in
      bacterial membranes, was inhibitory against the membrane perforation activity of
      VP4. The disruption of membranes by VP4 involved the formation of pores of ~3 nm
      inner diameter in mammalian cells including permissive SV40 host cells.
      Altogether, these results support a central role of VP4 acting as a viroporin in
      the perforation of cellular membranes to trigger SV40 viral release.

PMID- 21738475
TI  - The N-glycan glycoprotein deglycosylation complex (Gpd) from Capnocytophaga
      canimorsus deglycosylates human IgG.
AB  - C. canimorsus 5 has the capacity to grow at the expenses of glycan moieties from
      host cells N-glycoproteins. Here, we show that C. canimorsus 5 also has the
      capacity to deglycosylate human IgG and we analyze the deglycosylation mechanism.
      We show that deglycosylation is achieved by a large complex spanning the outer
      membrane and consisting of the Gpd proteins and sialidase SiaC. GpdD, -G, -E and 
      F are surface-exposed outer membrane lipoproteins. GpdDEF could contribute to the
      binding of glycoproteins at the bacterial surface while GpdG is a endo-beta-N
      acetylglucosaminidase cleaving the N-linked oligosaccharide after the first N
      linked GlcNAc residue. GpdC, resembling a TonB-dependent OM transporter is
      presumed to import the oligosaccharide into the periplasm after its cleavage from
      the glycoprotein. The terminal sialic acid residue of the oligosaccharide is then
      removed by SiaC, a periplasm-exposed lipoprotein in direct contact with GpdC.
      Finally, most likely degradation of the oligosaccharide proceeds sequentially
      from the desialylated non reducing end by the action of periplasmic
      exoglycosidases, including beta-galactosidases, beta-N-Acetylhexosaminidases and
      alpha-mannosidases.

PMID- 21738476
TI  - Clathrin facilitates the morphogenesis of retrovirus particles.
AB  - The morphogenesis of retroviral particles is driven by Gag and GagPol proteins
      that provide the major structural component and enzymatic activities required for
      particle assembly and maturation. In addition, a number of cellular proteins are
      found in retrovirus particles; some of these are important for viral replication,
      but many lack a known functional role. One such protein is clathrin, which is
      assumed to be passively incorporated into virions due to its abundance at the
      plasma membrane. We found that clathrin is not only exceptionally abundant in
      highly purified HIV-1 particles but is recruited with high specificity. In
      particular, the HIV-1 Pol protein was absolutely required for clathrin
      incorporation and point mutations in reverse transcriptase or integrase domains
      of Pol could abolish incorporation. Clathrin was also specifically incorporated
      into other retrovirus particles, including members of the lentivirus (simian
      immunodeficiency virus, SIVmac), gammaretrovirus (murine leukemia virus, MLV) and
      betaretrovirus (Mason-Pfizer monkey virus, M-PMV) genera. However, unlike HIV-1,
      these other retroviruses recruited clathrin primarily using peptide motifs in
      their respective Gag proteins that mimicked motifs found in cellular clathrin
      adaptors. Perturbation of clathrin incorporation into these retroviruses, via
      mutagenesis of viral proteins, siRNA based clathrin depletion or adaptor protein
      (AP180) induced clathrin sequestration, had a range of effects on the accuracy of
      particle morphogenesis. These effects varied according to which retrovirus was
      examined, and included Gag and/or Pol protein destabilization, inhibition of
      particle assembly and reduction in virion infectivity. For each retrovirus
      examined, clathrin incorporation appeared to be important for optimal
      replication. These data indicate that a number of retroviruses employ clathrin to
      facilitate the accurate morphogenesis of infectious particles. We propose a model
      in which clathrin contributes to the spatial organization of Gag and Pol
      proteins, and thereby regulates proteolytic processing of virion components
      during particle assembly.

PMID- 21738477
TI  - Cyclic di-GMP is essential for the survival of the lyme disease spirochete in
      ticks.
AB  - Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many
      biological processes. Although its role in bacterial pathogenesis during
      mammalian infection has been documented, the role of c-di-GMP in a pathogen's
      life cycle within a vector host is less understood. The enzootic cycle of the
      Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an
      Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the
      diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To
      determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1
      deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious
      in the mammalian host but cannot survive in the tick vector. Microarray analyses
      revealed that expression of a four-gene operon involved in glycerol transport and
      metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1.
      In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol
      as the carbon source (BSK-glycerol). To determine the contribution of the
      glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which
      the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the
      rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo,
      the glp mutant is also infectious in mice but has reduced survival in ticks.
      Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully
      rescues the growth defect in BSK-glycerol medium and partially restores survival
      of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch
      in B. burgdorferi and plays a vital role in the tick part of the spirochetal
      enzootic cycle. This work provides the first evidence that c-di-GMP is essential
      for a pathogen's survival in its vector host.

PMID- 21738478
TI  - Identification of nine novel loci associated with white blood cell subtypes in a
      Japanese population.
AB  - White blood cells (WBCs) mediate immune systems and consist of various subtypes
      with distinct roles. Elucidation of the mechanism that regulates the counts of
      the WBC subtypes would provide useful insights into both the etiology of the
      immune system and disease pathogenesis. In this study, we report results of
      genome-wide association studies (GWAS) and a replication study for the counts of
      the 5 main WBC subtypes (neutrophils, lymphocytes, monocytes, basophils, and
      eosinophils) using 14,792 Japanese subjects enrolled in the BioBank Japan
      Project. We identified 12 significantly associated loci that satisfied the genome
      wide significance threshold of P<5.0*10(-8), of which 9 loci were novel (the CDK6
      locus for the neutrophil count; the ITGA4, MLZE, STXBP6 loci, and the MHC region
      for the monocyte count; the SLC45A3-NUCKS1, GATA2, NAALAD2, ERG loci for the
      basophil count). We further evaluated associations in the identified loci using
      15,600 subjects from Caucasian populations. These WBC subtype-related loci
      demonstrated a variety of patterns of pleiotropic associations within the WBC
      subtypes, or with total WBC count, platelet count, or red blood cell-related
      traits (n = 30,454), which suggests unique and common functional roles of these
      loci in the processes of hematopoiesis. This study should contribute to the
      understanding of the genetic backgrounds of the WBC subtypes and hematological
      traits.

PMID- 21738479
TI  - Genome-wide association study of white blood cell count in 16,388 African
      Americans: the continental origins and genetic epidemiology network (COGENT).
AB  - Total white blood cell (WBC) and neutrophil counts are lower among individuals of
      African descent due to the common African-derived "null" variant of the Duffy
      Antigen Receptor for Chemokines (DARC) gene. Additional common genetic
      polymorphisms were recently associated with total WBC and WBC sub-type levels in
      European and Japanese populations. No additional loci that account for WBC
      variability have been identified in African Americans. In order to address this,
      we performed a large genome-wide association study (GWAS) of total WBC and cell
      subtype counts in 16,388 African-American participants from 7 population-based
      cohorts available in the Continental Origins and Genetic Epidemiology Network. In
      addition to the DARC locus on chromosome 1q23, we identified two other regions
      (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5*10(
      8)). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which
      encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent
      evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic
      Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP
      (rs12149261) on chromosome 16q22 associated with WBC count is located in a large
      inter-chromosomal segmental duplication encompassing part of the hydrocephalus
      inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22
      association finding is most likely due to a genotyping artifact as a consequence
      of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21.
      Among the WBC loci recently identified in European or Japanese populations,
      replication was observed in our African-American meta-analysis for rs445 of CDK6
      on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In
      summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in
      African American and other populations. We also demonstrate that large inter
      chromosomal duplications can result in false positive associations in GWAS.

PMID- 21738481
TI  - A single sex pheromone receptor determines chemical response specificity of
      sexual behavior in the silkmoth Bombyx mori.
AB  - In insects and other animals, intraspecific communication between individuals of
      the opposite sex is mediated in part by chemical signals called sex pheromones.
      In most moth species, male moths rely heavily on species-specific sex pheromones
      emitted by female moths to identify and orient towards an appropriate mating
      partner among a large number of sympatric insect species. The silkmoth, Bombyx
      mori, utilizes the simplest possible pheromone system, in which a single
      pheromone component, (E, Z)-10,12-hexadecadienol (bombykol), is sufficient to
      elicit full sexual behavior. We have previously shown that the sex pheromone
      receptor BmOR1 mediates specific detection of bombykol in the antennae of male
      silkmoths. However, it is unclear whether the sex pheromone receptor is the
      minimally sufficient determination factor that triggers initiation of orientation
      behavior towards a potential mate. Using transgenic silkmoths expressing the sex
      pheromone receptor PxOR1 of the diamondback moth Plutella xylostella in BmOR1
      expressing neurons, we show that the selectivity of the sex pheromone receptor
      determines the chemical response specificity of sexual behavior in the silkmoth.
      Bombykol receptor neurons expressing PxOR1 responded to its specific ligand, (Z)
      11-hexadecenal (Z11-16:Ald), in a dose-dependent manner. Male moths expressing
      PxOR1 exhibited typical pheromone orientation behavior and copulation attempts in
      response to Z11-16:Ald and to females of P. xylostella. Transformation of the
      bombykol receptor neurons had no effect on their projections in the antennal
      lobe. These results indicate that activation of bombykol receptor neurons alone
      is sufficient to trigger full sexual behavior. Thus, a single gene defines
      behavioral selectivity in sex pheromone communication in the silkmoth. Our
      findings show that a single molecular determinant can not only function as a
      modulator of behavior but also as an all-or-nothing initiator of a complex
      species-specific behavioral sequence.

PMID- 21738480
TI  - Multiple loci are associated with white blood cell phenotypes.
AB  - White blood cell (WBC) count is a common clinical measure from complete blood
      count assays, and it varies widely among healthy individuals. Total WBC count and
      its constituent subtypes have been shown to be moderately heritable, with the
      heritability estimates varying across cell types. We studied 19,509 subjects from
      seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for
      replication analyses, to determine genetic factors influencing variability within
      the normal hematological range for total WBC count and five WBC subtype measures.
      Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as
      well as independent collaborative studies. We identified and replicated ten
      associations with total WBC count and five WBC subtypes at seven different
      genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and
      CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27;
      lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24
      an intergenic region, 9q31 near EDG2), including three previously reported
      associations and seven novel associations. To investigate functional
      relationships among variants contributing to variability in the six WBC traits,
      we utilized gene expression- and pathways-based analyses. We implemented gene
      clustering algorithms to evaluate functional connectivity among implicated loci
      and showed functional relationships across cell types. Gene expression data from
      whole blood was utilized to show that significant biological consequences can be
      extracted from our genome-wide analyses, with effect estimates for significant
      loci from the meta-analyses being highly corellated with the proximal gene
      expression. In addition, collaborative efforts between the groups contributing to
      this study and related studies conducted by the COGENT and RIKEN groups allowed
      for the examination of effect homogeneity for genome-wide significant
      associations across populations of diverse ancestral backgrounds.

PMID- 21738482
TI  - Independent chromatin binding of ARGONAUTE4 and SPT5L/KTF1 mediates
      transcriptional gene silencing.
AB  - Eukaryotic genomes contain significant amounts of transposons and repetitive DNA
      elements, which, if transcribed, can be detrimental to the organism. Expression
      of these elements is suppressed by establishment of repressive chromatin
      modifications. In Arabidopsis thaliana, they are silenced by the siRNA-mediated
      transcriptional gene silencing pathway where long non-coding RNAs (lncRNAs)
      produced by RNA Polymerase V (Pol V) guide ARGONAUTE4 (AGO4) to chromatin and
      attract enzymes that establish repressive chromatin modifications. It is unknown
      how chromatin modifying enzymes are recruited to chromatin. We show through
      chromatin immunoprecipitation (ChIP) that SPT5L/KTF1, a silencing factor and a
      homolog of SPT5 elongation factors, binds chromatin at loci subject to
      transcriptional silencing. Chromatin binding of SPT5L/KTF1 occurs downstream of
      RNA Polymerase V, but independently from the presence of 24-nt siRNA. We also
      show that SPT5L/KTF1 and AGO4 are recruited to chromatin in parallel and
      independently of each other. As shown using methylation-sensitive restriction
      enzymes, binding of both AGO4 and SPT5L/KTF1 is required for DNA methylation and
      repressive histone modifications of several loci. We propose that the coordinate
      binding of SPT5L and AGO4 creates a platform for direct or indirect recruitment
      of chromatin modifying enzymes.

PMID- 21738483
TI  - A functional variant in microRNA-146a promoter modulates its expression and
      confers disease risk for systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong
      genetic predisposition, characterized by an upregulated type I interferon
      pathway. MicroRNAs are important regulators of immune homeostasis, and aberrant
      microRNA expression has been demonstrated in patients with autoimmune diseases.
      We recently identified miR-146a as a negative regulator of the interferon pathway
      and linked the abnormal activation of this pathway to the underexpression of miR
      146a in SLE patients. To explore why the expression of miR-146a is reduced in SLE
      patients, we conducted short parallel sequencing of potentially regulatory
      regions of miR-146a and identified a novel genetic variant (rs57095329) in the
      promoter region exhibiting evidence for association with SLE that was replicated
      independently in 7,182 Asians (P(meta) = 2.74*10(-8), odds ratio = 1.29 [1.18
      1.40]). The risk-associated G allele was linked to reduced expression of miR-146a
      in the peripheral blood leukocytes of the controls. Combined functional assays
      showed that the risk-associated G allele reduced the protein-binding affinity and
      activity of the promoter compared with those of the promoter containing the
      protective A allele. Transcription factor Ets-1, encoded by the lupus
      susceptibility gene ETS1, identified in recent genome-wide association studies,
      binds near this variant. The manipulation of Ets-1 levels strongly affected miR
      146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its
      reduced expression in SLE, directly impaired the induction of miR-146a. We also
      observed additive effects of the risk alleles of miR-146a and ETS1. Our data
      identified and confirmed an association between a functional promoter variant of
      miR-146a and SLE. This risk allele had decreased binding to transcription factor
      Ets-1, contributing to reduced levels of miR-146a in SLE patients.

PMID- 21738484
TI  - Genome-wide association of bipolar disorder suggests an enrichment of replicable
      associations in regions near genes.
AB  - Although a highly heritable and disabling disease, bipolar disorder's (BD)
      genetic variants have been challenging to identify. We present new genotype data
      for 1,190 cases and 401 controls and perform a genome-wide association study
      including additional samples for a total of 2,191 cases and 1,434 controls. We do
      not detect genome-wide significant associations for individual loci; however,
      across all SNPs, we show an association between the power to detect effects
      calculated from a previous genome-wide association study and evidence for
      replication (P = 1.5*10(-7)). To demonstrate that this result is not likely to be
      a false positive, we analyze replication rates in a large meta-analysis of height
      and show that, in a large enough study, associations replicate as a function of
      power, approaching a linear relationship. Within BD, SNPs near exons exhibit a
      greater probability of replication, supporting an enrichment of reproducible
      associations near functional regions of genes. These results indicate that there
      is likely common genetic variation associated with BD near exons (+/-10 kb) that
      could be identified in larger studies and, further, provide a framework for
      assessing the potential for replication when combining results from multiple
      studies.

PMID- 21738485
TI  - Genetic determinants of lipid traits in diverse populations from the population
      architecture using genomics and epidemiology (PAGE) study.
AB  - For the past five years, genome-wide association studies (GWAS) have identified
      hundreds of common variants associated with human diseases and traits, including
      high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol
      (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with
      lipid levels have been identified primarily among populations of European
      ancestry. The Population Architecture using Genomics and Epidemiology (PAGE)
      study was established in 2008 to characterize GWAS-identified variants in diverse
      population-based studies. We genotyped 49 GWAS-identified SNPs associated with
      one or more lipid traits in at least two PAGE studies and across six
      racial/ethnic groups. We performed a meta-analysis testing for SNP associations
      with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American
      (~20,000), African American (~9,000), American Indian (~6,000), Mexican
      American/Hispanic (~2,500), Japanese/East Asian (~690), and Pacific
      Islander/Native Hawaiian (~175) adults, regardless of lipid-lowering medication
      use. We replicated 55 of 60 (92%) SNP associations tested in European Americans
      at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268
      and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL
      C and MAFB rs6102059 previously associated with LDL-C. Based on significance
      (p<0.05) and consistent direction of effect, a majority of replicated genotype
      phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans
      generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%,
      and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16
      associations generalized across all three populations. For the associations that
      did not generalize, differences in effect sizes, allele frequencies, and linkage
      disequilibrium offer clues to the next generation of association studies for
      these traits.

PMID- 21738486
TI  - Maps of open chromatin guide the functional follow-up of genome-wide association
      signals: application to hematological traits.
AB  - Turning genetic discoveries identified in genome-wide association (GWA) studies
      into biological mechanisms is an important challenge in human genetics. Many GWA
      signals map outside exons, suggesting that the associated variants may lie within
      regulatory regions. We applied the formaldehyde-assisted isolation of regulatory
      elements (FAIRE) method in a megakaryocytic and an erythroblastoid cell line to
      map active regulatory elements at known loci associated with hematological
      quantitative traits, coronary artery disease, and myocardial infarction. We
      showed that the two cell types exhibit distinct patterns of open chromatin and
      that cell-specific open chromatin can guide the finding of functional variants.
      We identified an open chromatin region at chromosome 7q22.3 in megakaryocytes but
      not erythroblasts, which harbors the common non-coding sequence variant rs342293
      known to be associated with platelet volume and function. Resequencing of this
      open chromatin region in 643 individuals provided strong evidence that rs342293
      is the only putative causative variant in this region. We demonstrated that the C
      and G-alleles differentially bind the transcription factor EVI1 affecting PIK3CG
      gene expression in platelets and macrophages. A protein-protein interaction
      network including up- and down-regulated genes in Pik3cg knockout mice indicated
      that PIK3CG is associated with gene pathways with an established role in platelet
      membrane biogenesis and thrombus formation. Thus, rs342293 is the functional
      common variant at this locus; to the best of our knowledge this is the first such
      variant to be elucidated among the known platelet quantitative trait loci (QTLs).
      Our data suggested a molecular mechanism by which a non-coding GWA index SNP
      modulates platelet phenotype.

PMID- 21738487
TI  - Web-based genome-wide association study identifies two novel loci and a
      substantial genetic component for Parkinson's disease.
AB  - Although the causes of Parkinson's disease (PD) are thought to be primarily
      environmental, recent studies suggest that a number of genes influence
      susceptibility. Using targeted case recruitment and online survey instruments, we
      conducted the largest case-control genome-wide association study (GWAS) of PD
      based on a single collection of individuals to date (3,426 cases and 29,624
      controls). We discovered two novel, genome-wide significant associations with PD
      rs6812193 near SCARB2 (p = 7.6 * 10(-10), OR = 0.84) and rs11868035 near
      SREBF1/RAI1 (p = 5.6 * 10(-8), OR = 0.85)-both replicated in an independent
      cohort. We also replicated 20 previously discovered genetic associations
      (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support
      for our novel study design. Relying on a recently proposed method based on genome
      wide sharing estimates between distantly related individuals, we estimated the
      heritability of PD to be at least 0.27. Finally, using sparse regression
      techniques, we constructed predictive models that account for 6%-7% of the total
      variance in liability and that suggest the presence of true associations just
      beyond genome-wide significance, as confirmed through both internal and external
      cross-validation. These results indicate a substantial, but by no means total,
      contribution of genetics underlying susceptibility to both early-onset and late
      onset PD, suggesting that, despite the novel associations discovered here and
      elsewhere, the majority of the genetic component for Parkinson's disease remains
      to be discovered.

PMID- 21738489
TI  - Dynamic chromatin localization of Sirt6 shapes stress- and aging-related
      transcriptional networks.
AB  - The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in
      gene regulation and lifespan control. Sirt6 can interact with the stress
      responsive transcription factor NF-kappaB and regulate some NF-kappaB target
      genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6
      occupancy on chromatin are not known. Here we map Sirt6 occupancy on mouse
      promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response
      to TNF-alpha. More than half of Sirt6 target genes are only revealed upon stress
      signaling. The majority of genes bound by NF-kappaB subunit RelA recruit Sirt6,
      and dynamic Sirt6 relocalization is largely driven in a RelA-dependent manner.
      Integrative analysis with global gene expression patterns in wild-type, Sirt6-/-,
      and double Sirt6-/- RelA-/- cells reveals the epistatic relationships between
      Sirt6 and RelA in shaping diverse temporal patterns of gene expression. Genes
      under the direct joint control of Sirt6 and RelA include several with prominent
      roles in cell senescence and organismal aging. These data suggest dynamic
      chromatin relocalization of Sirt6 as a key output of NF-kappaB signaling in
      stress response and aging.

PMID- 21738488
TI  - A two-stage meta-analysis identifies several new loci for Parkinson's disease.
AB  - A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and
      21,026 controls conducted by the International Parkinson's Disease Genomics
      Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This
      first analysis of the two-stage IPDGC study focused on the set of loci that
      passed genome-wide significance in the first stage GWA scan. However, the second
      stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs
      selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920
      SNPs, and we identified five additional PD risk loci (combined p<5*10(-10),
      PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these
      five loci have been suggested by previous association studies (PARK16/1q32,
      FGF20/8p22), and this study provides further support for these findings. Using a
      dataset of post-mortem brain samples assayed for gene expression (n = 399) and
      methylation (n = 292), we identified methylation and expression changes
      associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11
      loci, hence suggesting potential molecular mechanisms and candidate genes at
      these risk loci.

PMID- 21738490
TI  - Role of the single-stranded DNA-binding protein SsbB in pneumococcal
      transformation: maintenance of a reservoir for genetic plasticity.
AB  - Bacteria encode a single-stranded DNA (ssDNA) binding protein (SSB) crucial for
      genome maintenance. In Bacillus subtilis and Streptococcus pneumoniae, an
      alternative SSB, SsbB, is expressed uniquely during competence for genetic
      transformation, but its precise role has been disappointingly obscure. Here, we
      report our investigations involving comparison of a null mutant (ssbB(-)) and a C
      ter truncation (ssbBDelta7) of SsbB of S. pneumoniae, the latter constructed
      because SSBs' acidic tail has emerged as a key site for interactions with partner
      proteins. We provide evidence that SsbB directly protects internalized ssDNA. We
      show that SsbB is highly abundant, potentially allowing the binding of ~1.15 Mb
      ssDNA (half a genome equivalent); that it participates in the processing of ssDNA
      into recombinants; and that, at high DNA concentration, it is of crucial
      importance for chromosomal transformation whilst antagonizing plasmid
      transformation. While the latter observation explains a long-standing observation
      that plasmid transformation is very inefficient in S. pneumoniae (compared to
      chromosomal transformation), the former supports our previous suggestion that
      SsbB creates a reservoir of ssDNA, allowing successive recombination cycles.
      SsbBDelta7 fulfils the reservoir function, suggesting that SsbB C-ter is not
      necessary for processing protein(s) to access stored ssDNA. We propose that the
      evolutionary raison d'etre of SsbB and its abundance is maintenance of this
      reservoir, which contributes to the genetic plasticity of S. pneumoniae by
      increasing the likelihood of multiple transformation events in the same cell.

PMID- 21738491
TI  - Identification of a sudden cardiac death susceptibility locus at 2q24.2 through
      genome-wide association in European ancestry individuals.
AB  - Sudden cardiac death (SCD) continues to be one of the leading causes of mortality
      worldwide, with an annual incidence estimated at 250,000-300,000 in the United
      States and with the vast majority occurring in the setting of coronary disease.
      We performed a genome-wide association meta-analysis in 1,283 SCD cases and
      >20,000 control individuals of European ancestry from 5 studies, with follow-up
      genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry
      studies, and identify the BAZ2B locus as associated with SCD (P = 1.8*10(-10)).
      The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong
      negative selection and increases risk for SCD by 1.92-fold per allele (95% CI
      1.57-2.34). We also tested the role of 49 SNPs previously implicated in
      modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent
      with epidemiological studies showing increased risk of SCD with prolonged QRS/QT
      intervals, the interval-prolonging alleles are in aggregate associated with
      increased risk for SCD (P = 0.006).

PMID- 21738492
TI  - Transportin-SR is required for proper splicing of resistance genes and plant
      immunity.
AB  - Transportin-SR (TRN-SR) is a member of the importin-beta super-family that
      functions as the nuclear import receptor for serine-arginine rich (SR) proteins,
      which play diverse roles in RNA metabolism. Here we report the identification and
      cloning of mos14 (modifier of snc1-1, 14), a mutation that suppresses the immune
      responses conditioned by the auto-activated Resistance (R) protein snc1
      (suppressor of npr1-1, constitutive 1). MOS14 encodes a nuclear protein with high
      similarity to previously characterized TRN-SR proteins in animals. Yeast two
      hybrid assays showed that MOS14 interacts with AtRAN1 via its N-terminus and SR
      proteins via its C-terminus. In mos14-1, localization of several SR proteins to
      the nucleus was impaired, confirming that MOS14 functions as a TRN-SR. The mos14
      1 mutation results in altered splicing patterns of SNC1 and another R gene RPS4
      and compromised resistance mediated by snc1 and RPS4, suggesting that nuclear
      import of SR proteins by MOS14 is required for proper splicing of these two R
      genes and is important for their functions in plant immunity.

PMID- 21738493
TI  - Telomere DNA deficiency is associated with development of human embryonic
      aneuploidy.
AB  - Aneuploidy represents the most prevalent form of genetic instability found in
      human embryos and is the leading genetic cause of miscarriage and developmental
      delay in newborns. Telomere DNA deficiency is associated with genomic instability
      in somatic cells and may play a role in development of aneuploidy commonly found
      in female germ cells and human embryos. To test this hypothesis, we developed a
      method capable of quantifying telomere DNA in parallel with 24-chromosome
      aneuploidy screening from the same oocyte or embryo biopsy. Aneuploid human polar
      bodies possessed significantly less telomere DNA than euploid polar bodies from
      sibling oocytes (-3.07 fold, P = 0.016). This indicates that oocytes with
      telomere DNA deficiency are prone to aneuploidy development during meiosis.
      Aneuploid embryonic cells also possessed significantly less telomere DNA than
      euploid embryonic cells at the cleavage stage (-2.60 fold, P = 0.002) but not at
      the blastocyst stage (-1.18 fold, P = 0.340). The lack of a significant
      difference at the blastocyst stage was found to be due to telomere DNA
      normalization between the cleavage and blastocyst stage of embryogenesis and not
      due to developmental arrest of embryos with short telomeres. Heterogeneity in
      telomere length within oocytes may provide an opportunity to improve the
      treatment of infertility through telomere-based selection of oocytes and embryos
      with reproductive competence.

PMID- 21738495
TI  - Synthesis, Characterization, Crystal Structure, and Biological Studies of a
      Cadmium(II) Complex with a Tridentate Ligand 4'-Chloro-2,2':6',2''-Terpyridine.
AB  - A new Cd(II) complex with the ligand 4'-chloro-2,2'6',2''-terpyridine (Cltpy),
      [Cd(Cltpy)(I)(2)], has been synthesized and characterized by CHN elemental
      analysis, (1)H-NMR, (13)C-NMR, and IR spectroscopy and structurally analyzed by X
      ray single-crystal diffraction. The single-crystal X-ray analyses show that the
      coordination number in complex is five with three terpyridine (Cltpy) N-donor
      atoms and two iodine atoms. The antibacterial activities of Cltpy and its Cd(II)
      complex are tested against different bacteria.

PMID- 21738494
TI  - Cryptic transcription mediates repression of subtelomeric metal homeostasis
      genes.
AB  - Nonsense-mediated mRNA decay (NMD) prevents the accumulation of transcripts
      bearing premature termination codons. Here we show that Saccharomyces cerevisiae
      NMD mutants accumulate 5'-extended RNAs (CD-CUTs) of many subtelomeric genes.
      Using the subtelomeric ZRT1 and FIT3 genes activated in response to zinc and iron
      deficiency, respectively, we show that transcription of these CD-CUTs mediates
      repression at the bona fide promoters, by preventing premature binding of RNA
      polymerase II in conditions of metal repletion. Expression of the main ZRT1 CD
      CUT is controlled by the histone deacetylase Rpd3p, showing that histone
      deacetylases can regulate expression of genes through modulation of the level of
      CD-CUTs. Analysis of binding of the transcriptional activator Zap1p and insertion
      of transcriptional terminators upstream from the Zap1p binding sites show that CD
      CUT transcription or accumulation also interferes with binding of the
      transcriptional activator Zap1p. Consistent with this model, overexpressing Zap1p
      or using a constitutively active version of the Aft1p transcriptional activator
      rescues the induction defect of ZRT1 and FIT3 in NMD mutants. These results show
      that cryptic upstream sense transcription resulting in unstable transcripts
      degraded by NMD controls repression of a large number of genes located in
      subtelomeric regions, and in particular of many metal homeostasis genes.

PMID- 21738496
TI  - Control of mRNA stability by SAPKs.
AB  - Control of mRNA turnover is an essential step in the regulation of gene
      expression in eukaryotes. The concerted action of many enzymes regulates the way
      each mRNA is degraded. Moreover, the degradation of each mRNA is influenced by
      the environment surrounding the cell. The conection between the environment and
      changes in the half-lifes of mRNAs is regulated by the activity of stress
      activated MAP kinases (SAPKs) and their substrates. Here we will describe some of
      those mechanisms, and how SAPKs regulate mRNA stability in eukaryotic cells.

PMID- 21738497
TI  - Postnatal development of dendrodendritic inhibition in the Mammalian olfactory
      bulb.
AB  - The mitral-granule cell (MC-GC) reciprocal synapse is an important source of auto
      and lateral-inhibition in the olfactory bulb (OB), and this local inhibition is
      critical for odor discrimination. We may gain insight into the role of MC
      autoinhibition in olfaction by correlating the functional development of the
      autoinhibition with the postnatal development of olfactory function. We have
      studied the functional development of the MC-GC reciprocal synapse using whole
      cell patch-clamp recordings from MCs and GCs in acute OB slices from 3- to 30-day
      old rats. The magnitude of dendrodendritic inhibition (DDI) measured by
      depolarizing a single MC and recording recurrent inhibition in the same cell
      increased up to the fifteenth day of life (P15), but dropped between P15 and P30.
      The initial increase and later decrease in DDI was echoed by a similar increase
      and decrease in the frequency of miniature inhibitory post-synaptic currents,
      suggesting an accompanying modulation in the number of synapses available to
      participate in DDI. The late decrease in DDI could also result, in part, from a
      decrease in GC excitability as well as an increase in relative contribution of N
      methyl d-aspartate (NMDA) receptors to gamma-amino butyric acid (GABA) release
      from GC synapses. Changes in release probability of GABAergic synapses are
      unlikely to account for the late reduction in DDI, although they might contribute
      to the early increase during development. Our results demonstrate that the
      functional MC-GC circuit evolves over development in a complex manner that may
      include both construction and elimination of synapses.

PMID- 21738498
TI  - The role of collybistin in gephyrin clustering at inhibitory synapses: facts and
      open questions.
AB  - Collybistin (Cb) is a brain-specific GDP/GTP-exchange factor, which interacts
      with the inhibitory receptor anchoring protein gephyrin. Data from mice carrying
      an inactivated Cb gene indicate that Cb is required for the formation and
      maintenance of gephyrin and gephyrin-dependent GABA(A) receptor (GABA(A)R)
      clusters at inhibitory postsynapses in selected regions of the mammalian
      forebrain. However, important aspects of how Cb's GDP/GTP-exchange activity,
      structure, and regulation contribute to gephyrin and GABA(A)R clustering, as well
      as its role in synaptic plasticity, remain poorly understood. Here we review the
      current state of knowledge about Cb's function and address open questions
      concerning its contribution to synapse formation, maintenance, plasticity, and
      adaptive changes in response to altered network activity.

PMID- 21738499
TI  - The structural, functional, and molecular organization of the brainstem.
AB  - According to His (1891, 1893) the brainstem consists of two longitudinal zones,
      the dorsal alar plate (sensory in nature) and the ventral basal plate (motor in
      nature). Johnston and Herrick indicated that both plates can be subdivided into
      separate somatic and visceral zones, distinguishing somatosensory and
      viscerosensory zones within the alar plate, and visceromotor and somatomotor
      zones within the basal plate. To test the validity of this "four-functional
      zones" concept, I developed a topological procedure, surveying the spatial
      relationships of the various cell masses in the brainstem in a single figure.
      Brainstems of 16 different anamniote species were analyzed, and revealed that the
      brainstems are clearly divisible into four morphological zones, which correspond
      largely with the functional zones of Johnston and Herrick. Exceptions include (1)
      the magnocellular vestibular nucleus situated in the viscerosensory zone; (2) the
      basal plate containing a number of evidently non-motor centers (superior and
      inferior olives). Nevertheless the "functional zonal model" has explanatory
      value. Thus, it is possible to interpret certain brain specializations related to
      particular behavioral profiles, as "local hypertrophies" of one or two functional
      columns. Recent developmental molecular studies on brains of birds and mammals
      confirmed the presence of longitudinal zones, and also showed molecularly defined
      transverse bands or neuromeres throughout development. The intersecting
      boundaries of the longitudinal zones and the transverse bands appeared to delimit
      radially arranged histogenetic domains. Because neuromeres have been observed in
      embryonic and larval stages of numerous anamniote species, it may be hypothesized
      that the brainstems of all vertebrates share a basic organizational plan, in
      which intersecting longitudinal and transverse zones form fundamental
      histogenetic and genoarchitectonic units.

PMID- 21738500
TI  - Modulating affect, cognition, and behavior - prospects of deep brain stimulation
      for treatment-resistant psychiatric disorders.
AB  - Most patients suffering from psychiatric disorders respond to combinations of
      psycho- and psychopharmacotherapy; however there are patients who profit little
      if anything even after many years of treatment. Since about a decade different
      modalities of targeted neuromodulation - among them most prominently - deep brain
      stimulation (DBS) - are being actively researched as putative approaches to very
      treatment-resistant forms of those disorders. Recently, promising pilot data have
      been reported both for major depression (MD) and obsessive-compulsive disorder
      (OCD). Given the fact that patients included in DBS studies had been treated
      unsuccessfully for many years with conventional treatment methods, renders these
      findings remarkable. Remarkable is the fact, that in case of the long-term
      studies underway for MD, patients show a stable response. This gives hope to a
      substantial percentage of therapy-resistant psychiatric patients requiring new
      therapy approaches. There are no fundamental ethic objections to its use in
      psychiatric disorders, but until substantial clinical data is available,
      mandatory standards are needed. DBS is a unique and very promising method for the
      treatment of therapy-resistant psychiatric patients. The method allows
      manipulating pathological neuronal networks in a very precise way.

PMID- 21738501
TI  - Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the
      Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval.
AB  - We have studied the influence of pre-training psychological stress on the
      expression of c-fos mRNA following long-term spatial memory retrieval. Rats were
      trained to learn the location of a hidden escape platform in the radial-arm water
      maze, and then their memory for the platform location was assessed 24 h later.
      Rat brains were extracted 30 min after the 24-h memory test trial for analysis of
      c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard);
      (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre
      Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats
      given no water exposure (Home Cage). The Standard trained group exhibited
      excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal
      hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no
      increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group
      were classified into two subgroups: good and bad memory performers. Neither of
      the two Pre-Training Stress subgroups exhibited a significant change in c-fos
      mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with
      good memory exhibited significantly greater c-fos mRNA expression in the
      dorsolateral striatum (DLS) compared to stressed rats with bad memory. This
      finding suggests that stressed rats with good memory used their DLS to generate a
      non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of
      the platform location. Collectively, these findings provide evidence at a
      molecular level for the involvement of the hippocampus and BLA in the retrieval
      of spatial memory and contribute novel observations on the influence of pre
      training stress in activating the DLS in response to long-term memory retrieval.

PMID- 21738502
TI  - Subcutaneous plasmacytoma metastasis precipitated by tunneled central venous
      catheter insertion.
AB  - Extramedullary plasmacytomas are tumors of monoclonal plasma cells arising within
      soft tissue that uncommonly occur in multiple myeloma patients. While sporadic
      development of these tumors at cutaneous trauma sites, including venous catheter
      access sites, has been reported, interventional radiologists seldom encounter
      this disease. Herein, we describe a case of metastatic subcutaneous plasmacytoma
      precipitated by tunneled central venous catheter insertion in a male patient
      undergoing stem cell therapy for treatment of multiple myeloma. In addition, we
      review the identification, diagnostic pitfalls, pathogenesis, and treatment of
      this rare entity.

PMID- 21738503
TI  - Imatinib treatment alone in Philadelphia-positive acute lymphoblastic leukemia:
      is it enough?
AB  - BCR-ABL fusion gene t(9;22)(q34;q11) occurs in only 3% of pediatric acute
      lymphoblastic leukemia (ALL) cases. Previously, less than 40% of Philadelphia
      positive ALL patients were cured with intensive chemotherapy. The use of imatinib
      (340 mg/m(2)/day) added to an intensive chemotherapy regimen has improved the
      outcome in this population at 3 years to an event-free survival of 80%. Imatinib
      treatment alone was administered after remission induction chemotherapy to a
      patient with Philadelphia-positive ALL who presented with serious chemotherapy
      toxicity, so that intensive chemotherapy could not be maintained. This is the
      only patient in the literature who survived remission for more than 2.5 years
      with imatinib treatment only.

PMID- 21738504
TI  - A case of advanced hepatocellular carcinoma with portal vein tumor thrombus
      refractory to epirubicin that showed marked decrease in tumor markers after
      transcatheter arterial infusion with miriplatin.
AB  - Miriplatin, a cisplatin derivative with a high affinity for iodized ethyl esters
      of fatty acids from poppy seed oil, is a novel chemotherapeutic agent designed
      for use in the transarterial treatment of hepatocellular carcinoma (HCC). Here,
      we describe transcatheter arterial infusion (TAI) using miriplatin to treat a
      case of advanced HCC with portal vein tumor thrombus (PVTT) refractory to TAI
      with epirubicin. A 66-year-old man with advanced hepatitis C virus-related HCC
      with PVTT in the right lobe of the liver was treated with TAI with epirubicin
      suspended in iodized oil; however, tumor marker levels (alpha-fetoprotein and des
      gamma-carboxy protein) did not decrease. Next, he was treated twice with TAI with
      miriplatin suspended in iodized oil. The tumor marker levels markedly decreased
      to a nearly normal range and the size of the main tumor was markedly reduced
      according to dynamic computed tomography. No serious adverse events occurred
      during the course of treatment with TAI and miriplatin. Therefore, we suggest
      that TAI with miriplatin is a safe and effective treatment option for advanced
      HCCs refractory to TAI with epirubicin.

PMID- 21738505
TI  - Acute demyelinating disease after oral therapy with herbal extracts.
AB  - Central nervous system demyelinating processes such as multiple sclerosis and
      acute disseminated encephalomyelitis constitute a group of diseases not
      completely understood in their physiopathology. Environmental and toxic insults
      are thought to play a role in priming autoimmunity. The aim of the present report
      is to describe a case of acute demyelinating disease with fatal outcome occurring
      15 days after oral exposure to herbal extracts.

PMID- 21738506
TI  - Extensive Spinal Cord Injury following Staphylococcus aureus Septicemia and
      Meningitis.
AB  - Bacterial meningitis is rarely complicated by spinal cord involvement in adults.
      We report a case of Staphylococcus aureus septicemia complicated by meningitis
      and extensive spinal cord injury, leading to ascending brain stem necrosis and
      death. This complication was investigated by magnetic resonance imaging which
      demonstrated intramedullary hyperintensity on T2-weighted images and by
      multimodality evoked potentials. Postmortem microscopic examination confirmed
      that the extensive spinal cord injury was of ischemic origin, caused by diffuse
      leptomeningitis and endarteritis.

PMID- 21738507
TI  - Ethnodiagnostic skills of the digo community for malaria: a lead to traditional
      bioprospecting.
AB  - Malaria is a major public health problem that is presently complicated by the
      development of resistance by Plasmodium falciparum to the mainstay drugs. Thus,
      new drugs with unique structures and mechanism of action are required to treat
      drug-resistant strains of malaria. Historically, compounds containing a novel
      structure from natural origin represent a major source for the discovery and
      development of new drugs for several diseases. This paper presents
      ethnophytotherapeutic remedies, ethnodiagnostic skills, and related traditional
      knowledge utilized by the Digo community of the Kenyan Coast to diagnose malaria
      as a lead to traditional bioprospecting. The current study was carried out in
      three Digo villages of Diani sub-location between May 2009 and December 2009.
      Data was collected using semi-structured interviews, and open and close-ended
      questionnaires. A total of 60 respondents (34 men and 26 women) provided the
      targeted information. The results show that the indigenous knowledge of Digo
      community on malaria encompasses not only the symptoms of malaria but also the
      factors that are responsible for causing malaria, attributes favoring the
      breeding of mosquitoes and practices employed to guard against mosquito bites or
      to protect households against malaria. This knowledge is closely in harmony with
      scientific approaches to the treatment and control of the disease. The Digo
      community uses 60 medicinal plants distributed in 52 genera and 27 families to
      treat malaria. The most frequently mentioned symptoms were fever, joint pains,
      and vomiting while the most frequently mentioned practices employed to guard
      against mosquito bites and/or to protect households against malaria was burning
      of herbal plants such as Ocimum suave and ingestion of herbal decoctions and
      concoctions. The Digo community has abundant ethnodiagnostic skills for malaria
      which forms the basis of their traditional bioprospecting techniques.

PMID- 21738508
TI  - A single intracoronary injection of midkine reduces ischemia/reperfusion injury
      in Swine hearts: a novel therapeutic approach for acute coronary syndrome.
AB  - Several growth factors are effective for salvaging myocardium and limiting
      infarct size in experimental studies with small animals. Their benefit in large
      animals and feasibility in clinical practice remains to be elucidated. We
      investigated the cardioprotective effect of midkine (MK) in swine subjected to
      ischemia/reperfusion (I/R). I/R was created by left anterior descending coronary
      artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter.
      MK protein was injected as a bolus through the catheter at the initiation of
      reperfusion [MK-treated (MKT) group]. Saline was injected in controls (CONT).
      Infarct size/area at risk (24 h after I/R) in MKT was almost five times smaller
      than in CONT. Echocardiography in MKT revealed a significantly higher percent
      wall thickening of the interventricular septum, a higher left ventricular (LV)
      fractional shortening, and a lower E/e(') (ratio of transmitral to annular flow)
      compared with CONT. LV catheterization in MKT showed a lower LV end-diastolic
      pressure, and a higher dP/dt(max) compared with CONT. Terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP nick end-labeling-positive myocytes and CD45
      positive cell infiltration in the peri-infarct area were significantly less in
      MKT than in CONT. Here, we demonstrate that a single intracoronary injection of
      MK protein in swine hearts at the onset of reperfusion dramatically reduces
      infarct size and ameliorates systolic/diastolic LV function. This beneficial
      effect is associated with a reduction of apoptotic and inflammatory reactions. MK
      application during percutaneous coronary intervention may become a promising
      adjunctive therapy in acute coronary syndromes.

PMID- 21738509
TI  - The emergence of spanking among a representative sample of children under 2 years
      of age in north Carolina.
AB  - Spanking is common in the United States but less common in many European
      countries in which it has been outlawed. Being spanked has been associated with
      child abuse victimization, poor self-esteem, impaired parent-child relationships,
      and child and adult mental health, substance abuse, and behavioral consequences.
      Being spanked as a child has also been shown to increase the likelihood of
      abusing one's own children or spouse as an adult. Spanking of very young children
      less than two is almost never recommended even among experts that consider
      spanking as reasonable in some circumstances. Using a cross-sectional anonymous
      telephone survey, we describe spanking rates among a representative sample of
      North Carolina mothers of children less than 2 years old and the association of
      spanking with demographic characteristics. A substantial proportion of mothers
      admit to spanking their very young children. The rate of spanking in the last
      year among all maternal respondents was 30%. Over 5% of the mothers of 3-month
      olds reported spanking. Over 70% of the mothers of 23-month olds reported
      spanking. Increased spanking was associated with higher age of the child and
      lower maternal age. With every month of age, a child had 27% increased odds of
      being spanked. Early spanking has been shown to be associated with poor cognitive
      development in early childhood. Further, early trauma has been shown to have
      significant effects on the early developing brain. It is therefore critical that
      health and human services professionals address the risk of corporal punishment
      as a method of discipline early in the life of the child. The spanking of very
      young children may be an appropriate locus for policy and legislative debates
      regarding corporal punishment.

PMID- 21738510
TI  - Did insecure attachment styles evolve for the benefit of the group?

PMID- 21738511
TI  - Some Insults are Easier to Detect: The Embodied Insult Detection Effect.
AB  - In the present research we examined the effects of bodily experience on
      processing of insults in a series of semantic categorization tasks we call insult
      detection tasks (i.e., participants decided whether presented stimuli were
      insults or not). Two types of insults were used: more embodied insults (e.g.,
      asswipe, ugly), and less embodied insults (e.g., cheapskate, twit), as well as
      non-insults. In Experiments 1 and 2 the non-insults did not form a single,
      coherent category (e.g., airbase, polka), whereas in Experiment 3 all the non
      insults were compliments (e.g., eyeful, honest). Regardless of type of non-insult
      used, we observed facilitatory embodied insult effects such that more embodied
      insults were responded to faster and recalled more often than less embodied
      insults. In Experiment 4 we used a larger set of insults as stimuli, which
      allowed hierarchical multiple regression analyses. These analyses revealed that
      bodily experience ratings accounted for a significant amount of unique response
      latency, response error, and recall variability for responses to insults, even
      with several other predictor variables (e.g., frequency, offensiveness,
      imageability) included in the analyses: responses were faster and more accurate,
      and there was greater recall for relatively more embodied insults. These results
      demonstrate that conceptual knowledge of insults is grounded in knowledge gained
      through bodily experience.

PMID- 21738512
TI  - Where do action goals come from? Evidence for spontaneous action-effect binding
      in infants.
AB  - One of the great questions in psychology concerns how we develop to become
      intentional agents. Ideomotor theory suggests that intentional actions depend on,
      and emerge from the automatic acquisition of bidirectional action-effect
      associations: perceiving an action-effect sequence creates an integrated
      representation that can be employed for action control in the opposite order,
      selecting an action by anticipating its effect. We provide first evidence for the
      spontaneous acquisition of bidirectional action-effect associations in 9- 12-,
      and 18-month-olds, suggesting that the mechanism underlying action-effect
      integration is in place at the latest around 9 months of age.

PMID- 21738513
TI  - Segregation of vowels and consonants in human auditory cortex: evidence for
      distributed hierarchical organization.
AB  - The speech signal consists of a continuous stream of consonants and vowels, which
      must be de- and encoded in human auditory cortex to ensure the robust recognition
      and categorization of speech sounds. We used small-voxel functional magnetic
      resonance imaging to study information encoded in local brain activation patterns
      elicited by consonant-vowel syllables, and by a control set of noise bursts.
      First, activation of anterior-lateral superior temporal cortex was seen when
      controlling for unspecific acoustic processing (syllables versus band-passed
      noises, in a "classic" subtraction-based design). Second, a classifier algorithm,
      which was trained and tested iteratively on data from all subjects to
      discriminate local brain activation patterns, yielded separations of cortical
      patches discriminative of vowel category versus patches discriminative of stop
      consonant category across the entire superior temporal cortex, yet with regional
      differences in average classification accuracy. Overlap (voxels correctly
      classifying both speech sound categories) was surprisingly sparse. Third, lending
      further plausibility to the results, classification of speech-noise differences
      was generally superior to speech-speech classifications, with the no? exception
      of a left anterior region, where speech-speech classification accuracies were
      significantly better. These data demonstrate that acoustic-phonetic features are
      encoded in complex yet sparsely overlapping local patterns of neural activity
      distributed hierarchically across different regions of the auditory cortex. The
      redundancy apparent in these multiple patterns may partly explain the robustness
      of phonemic representations.

PMID- 21738514
TI  - What works with individuals in a clinical setting?

PMID- 21738515
TI  - Do intensive studies of a foreign language improve associative memory
      performance?
AB  - Formal education has been proposed to shape life-long cognitive development.
      Studies reporting that gains from cognitive training transfer to untrained tasks
      suggest direct effects of mental activity on cognitive processing efficiency.
      However, associative memory practice has not been known to produce transfer
      effects, which is odd considering that the key neural substrate of associative
      memory, the hippocampus, is known to be particularly plastic. We investigated
      whether extremely intensive studies of a foreign language, entailing demands on
      associative memory, cause improvements in associative memory performance. In a
      pretest-training-post-test design, military conscript interpreters and
      undergraduate students were measured on a battery of cognitive tasks. We found
      transfer from language studies to a face-name associative-memory task, but not to
      measures of working memory, strategy-sensitive episodic memory, or fluid
      intelligence. These findings provide initial evidence suggesting that associative
      memory performance can be improved in early adulthood, and that formal education
      can have such effects.

PMID- 21738516
TI  - How Different is Different? Criterion and Sensitivity in Face-Space.
AB  - Not all detectable differences between face images correspond to a change in
      identity. Here we measure both sensitivity to change and the criterion difference
      that is perceived as a change in identity. Both measures are used to test between
      possible similarity metrics. Using a same/different task and the method of
      constant stimuli criterion is specified as the 50% "different" point (P50) and
      sensitivity as the difference limen (DL). Stimuli and differences are defined
      within a "face-space" based on principal components analysis of measured
      differences in three-dimensional shape. In Experiment 1 we varied views
      available. Criterion (P50) was lowest for identical full-face view comparisons
      that can be based on image differences. When comparing across views P50, was the
      same for a static 45 degrees  change as for multiple animated views, although
      sensitivity (DL) was higher for the animated case, where it was as high as for
      identical views. Experiments 2 and 3 tested possible similarity metrics.
      Experiment 2 contrasted Euclidean and Mahalanobis distance by setting PC1 or PC2
      to zero. DL did not differ between conditions consistent with Mahalanobis. P50
      was lower when PC2 changed emphasizing that perceived changes in identity are not
      determined by the magnitude of Euclidean physical differences. Experiment 3
      contrasted a distance with an angle based similarity measure. We varied the
      distinctiveness of the faces being compared by varying distance from the origin,
      a manipulation that affects distances but not angles between faces. Angular P50
      and DL were both constant for faces from 1 to 2 SD from the mean, consistent with
      an angular measure. We conclude that both criterion and sensitivity need to be
      considered and that an angular similarity metric based on standardized PC values
      provides the best metric for specifying what physical differences will be
      perceived to change in identity.

PMID- 21738517
TI  - Spatial discounting of food and social rewards in guppies (poecilia reticulata).
AB  - In temporal discounting, animals trade off the time to obtain a reward against
      the quality of a reward, choosing between a smaller reward available sooner
      versus a larger reward available later. Similar discounting can apply over space,
      when animals choose between smaller and closer versus larger and more distant
      rewards. Most studies of temporal and spatial discounting in non-human animals
      use food as the reward, and it is not established whether animals trade off other
      preferred stimuli in similar ways. Here, we offered female guppies (Poecilia
      reticulata) a spatial discounting task in which we measured preferences for a
      larger reward as the distance to it increased relative to a closer but smaller
      reward. We tested whether the fish discounted reward types differently by
      offering subjects either food items or same-sex conspecifics as rewards. Before
      beginning the discounting tasks, we conducted validation tests to ensure that
      subjects equally valued the food and social stimuli in the quantities provided.
      In the discounting task, subjects switched their preferences from the larger to
      the smaller reward as the distance to the larger reward increased (spatial
      discounting), but the pattern and magnitude of discounting did not differ across
      the two reward types. These findings indicate that guppies show similar patterns
      of discounting for food and social rewards in a spatial task. In an examination
      of travel times, however, the fish swam faster to food rewards than to shoaling
      partners. Analysis of travel times suggests that fish temporally discounted
      social rewards less steeply than food rewards. Thus, reward type influences
      temporal discounting, suggesting a dissociation between temporal and spatial
      discounting. Our results illustrate how animals adjust choices and travel times
      depending on both the type of cost (time, distance) and benefits (food, social
      partners).

PMID- 21738518
TI  - The perception of musical spontaneity in improvised and imitated jazz
      performances.
AB  - The ability to evaluate spontaneity in human behavior is called upon in the
      esthetic appreciation of dramatic arts and music. The current study addresses the
      behavioral and brain mechanisms that mediate the perception of spontaneity in
      music performance. In a functional magnetic resonance imaging experiment, 22 jazz
      musicians listened to piano melodies and judged whether they were improvised or
      imitated. Judgment accuracy (mean 55%; range 44-65%), which was low but above
      chance, was positively correlated with musical experience and empathy. Analysis
      of listeners' hemodynamic responses revealed that amygdala activation was
      stronger for improvisations than imitations. This activation correlated with the
      variability of performance timing and intensity (loudness) in the melodies,
      suggesting that the amygdala is involved in the detection of behavioral
      uncertainty. An analysis based on the subjective classification of melodies
      according to listeners' judgments revealed that a network including the pre
      supplementary motor area, frontal operculum, and anterior insula was most
      strongly activated for melodies judged to be improvised. This may reflect the
      increased engagement of an action simulation network when melodic predictions are
      rendered challenging due to perceived instability in the performer's actions.
      Taken together, our results suggest that, while certain brain regions in skilled
      individuals may be generally sensitive to objective cues to spontaneity in human
      behavior, the ability to evaluate spontaneity accurately depends upon whether an
      individual's action-related experience and perspective taking skills enable
      faithful internal simulation of the given behavior.

PMID- 21738520
TI  - Accounting for Item Variance in Large-scale Databases.

PMID- 21738519
TI  - Transfer of Training between Music and Speech: Common Processing, Attention, and
      Memory.
AB  - After a brief historical perspective of the relationship between language and
      music, we review our work on transfer of training from music to speech that aimed
      at testing the general hypothesis that musicians should be more sensitive than
      non-musicians to speech sounds. In light of recent results in the literature, we
      argue that when long-term experience in one domain influences acoustic processing
      in the other domain, results can be interpreted as common acoustic processing.
      But when long-term experience in one domain influences the building-up of
      abstract and specific percepts in another domain, results are taken as evidence
      for transfer of training effects. Moreover, we also discuss the influence of
      attention and working memory on transfer effects and we highlight the usefulness
      of the event-related potentials method to disentangle the different processes
      that unfold in the course of music and speech perception. Finally, we give an
      overview of an on-going longitudinal project with children aimed at testing
      transfer effects from music to different levels and aspects of speech processing.

PMID- 21738521
TI  - Pinning down viral proteins: a new prototype for virus-host cell interaction.
AB  - Pin 1 is an enzyme that specifically catalyzes the cis-trans isomerization of
      phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif in its substrate
      proteins. Recent studies demonstrate that stability of several viral proteins is
      regulated by phosphorylation-dependent prolyl-isomerization by a host factor
      Pin1. Pin1 is now positioned as an important modulator of the molecular crosstalk
      between virus and host cells and could be a unique target for anti-virus therapy.
      This new type of post-translational modification by Pin1 might be involved in the
      regulation of other viral proteins.

PMID- 21738522
TI  - The Chlamydial Type III Secretion Mechanism: Revealing Cracks in a Tough Nut.
AB  - Present-day members of the Chlamydiaceae contain parasitic bacteria that have
      been co-evolving with their eukaryotic hosts over hundreds of millions of years.
      Likewise, a type III secretion system encoded within all genomes has been refined
      to complement the unique obligate intracellular niche colonized so successfully
      by Chlamydia spp. All this adaptation has occurred in the apparent absence of the
      horizontal gene transfer responsible for creating the wide range of diversity in
      other Gram-negative, type III-expressing bacteria. The result is a system that
      is, in many ways, uniquely chlamydial. A critical mass of information has been
      amassed that sheds significant light on how the chlamydial secretion system
      functions and contributes to an obligate intracellular lifestyle. Although the
      overall mechanism is certainly similar to homologous systems, an image has
      emerged where the chlamydial secretion system is essential for both survival and
      virulence. Numerous apparent differences, some subtle and some profound,
      differentiate chlamydial type III secretion from others. Herein, we provide a
      comprehensive review of the current state of knowledge regarding the Chlamydia
      type III secretion mechanism. We focus on the aspects that are distinctly
      chlamydial and comment on how this important system influences chlamydial
      pathogenesis. Gaining a grasp on this fascinating system has been challenging in
      the absence of a tractable genetic system. However, the surface of this tough nut
      has been scored and the future promises to be fruitful and revealing.

PMID- 21738523
TI  - Transcriptional profiling of mycobacterium tuberculosis during infection: lessons
      learned.
AB  - Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis,
      is considered one of the biggest infectious disease killers worldwide. A
      significant amount of attention has been directed toward revealing genes involved
      in the virulence and pathogenesis of this air-born pathogen. With the advances in
      technologies for transcriptional profiling, several groups, including ours, took
      advantage of DNA microarrays to identify transcriptional units differentially
      regulated by M. tuberculosis within a host. The main idea behind this approach is
      that pathogens tend to regulate their gene expression levels depending on the
      host microenvironment, and preferentially express those needed for survival.
      Identifying this class of genes will improve our understanding of pathogenesis.
      In our case, we identified an in vivo expressed genomic island that was
      preferentially active in murine lungs during early infection, as well as groups
      of genes active during chronic tuberculosis. Other studies have identified
      additional gene groups that are active during macrophage infection and even in
      human lungs. Despite all of these findings, one of the lingering questions
      remaining was whether in vivo expressed transcripts are relevant to the
      virulence, pathogenesis, and persistence of the organism. The work of our group
      and others addressed this question by examining the contribution of in vivo
      expressed genes using a strategy based on gene deletions followed by animal
      infections. Overall, the analysis of most of the in vivo expressed genes
      supported a role of these genes in M. tuberculosis pathogenesis. Further, these
      data suggest that in vivo transcriptional profiling is a valid approach to
      identify genes required for bacterial pathogenesis.

PMID- 21738524
TI  - Metatranscriptomic analysis of sulfur oxidation genes in the endosymbiont of
      solemya velum.
AB  - Thioautotrophic endosymbionts in the Domain Bacteria mediate key sulfur
      transformations in marine reducing environments. However, the molecular pathways
      underlying symbiont metabolism and the extent to which these pathways are
      expressed in situ are poorly characterized for almost all symbioses. This is
      largely due to the difficulty of culturing symbionts apart from their hosts.
      Here, we use pyrosequencing of community RNA transcripts (i.e., the
      metatranscriptome) to characterize enzymes of dissimilatory sulfur metabolism in
      the model symbiosis between the coastal bivalve Solemya velum and its
      intracellular thioautotrophic symbionts. High-throughput sequencing of total RNA
      from the symbiont-containing gill of a single host individual generated 1.6
      million sequence reads (500 Mbp). Of these, 43,735 matched Bacteria protein
      coding genes in BLASTX searches of the NCBI database. The taxonomic identities of
      the matched genes indicated relatedness to diverse species of sulfur-oxidizing
      Gammaproteobacteria, including other thioautotrophic symbionts and the purple
      sulfur bacterium Allochromatium vinosum. Manual querying of these data identified
      28 genes from diverse pathways of sulfur energy metabolism, including the
      dissimilatory sulfite reductase (Dsr) pathway for sulfur oxidation to sulfite,
      the APS pathway for sulfite oxidation, and the Sox pathway for thiosulfate
      oxidation. In total, reads matching sulfur energy metabolism genes represented 7%
      of the Bacteria mRNA pool. Together, these data highlight the dominance of
      thioautotrophy in the context of symbiont community metabolism, identify the
      likely pathways mediating sulfur oxidation, and illustrate the utility of
      metatranscriptome sequencing for characterizing community gene transcription of
      uncultured symbionts.

PMID- 21738525
TI  - Ribosomal protein s3: a multifunctional target of attaching/effacing bacterial
      pathogens.
AB  - The extraribosomal functions of ribosomal proteins have drawn significant recent
      attention. Ribosomal protein S3 (RPS3), a component of the eukaryotic 40S
      ribosomal subunit, is a multifunctional protein that regulates DNA repair,
      apoptosis, and the innate immune response to bacterial infection. Here we the
      review the latest findings about RPS3 extraribosomal functions, with special
      emphasis on their relation to microbial pathogenesis and enteropathogenic
      Escherichia coli.

PMID- 21738526
TI  - Pharmacokinetics of p-Aminohippuric Acid and Inulin in Rabbits with Aristolochic
      Acid Nephropathy.
AB  - The characteristics of aristolochic acid nephropathy (AAN) are interstitial
      fibrosis and atrophy of the proximal tubules, but with no change in glomeruli. To
      investigate the effects of AA on renal functions and the pharmacokinetics (PKs)
      of p-aminohippuric acid (PAH) and inulin, New Zealand white rabbits were used in
      this study. The plasma concentrations of PAH and inulin were determined by
      validated HPLC methods. After a single intravenous administration of 0.5 mg/kg
      aristolochic acid sodium (AANa), rabbits exhibited mild to moderate
      nephrotoxicity on the 7th day. Significant tubulointerstitial damage to kidney
      specimens was found, but there were no remarkable glomerular changes. Clearance
      rates of PAH and inulin both significantly decreased in AANa-treated rabbits. In
      addition, there was a significant correlation among the degree of
      tubulointerstitial changes and PK parameters of PAH after AANa administration,
      but no correlation was noted with the PKs of inulin. With mild to moderate AAN in
      rabbits, the renal plasma flow significantly decreased by 55%, and the glomerular
      filtration rate also significantly decreased by 85%. In conclusion, major renal
      lesions were found on proximal tubules after AANa administration. The PKs of PAH
      and inulin significantly changed, and kidney functions, including the RPF and
      GFR, were reduced.

PMID- 21738527
TI  - The pharmacology of acute lung injury in sepsis.
AB  - Acute lung injury (ALI) secondary to sepsis is one of the leading causes of death
      in sepsis. As such, many pharmacologic and nonpharmacologic strategies have been
      employed to attenuate its course. Very few of these strategies have proven
      beneficial. In this paper, we discuss the epidemiology and pathophysiology of
      ALI, commonly employed pharmacologic and nonpharmacologic treatments, and
      innovative therapeutic modalities that will likely be the focus of future trials.

PMID- 21738528
TI  - Differential Neuroprotection of Selective Estrogen Receptor Agonists against
      Autonomic Dysfunction and Ischemic Cell Death in Permanent versus Reperfusion
      Injury.
AB  - In the present study, we tested the hypothesis that selective activation of
      estrogen receptor subtypes (ERalpha and ERbeta) would be neuroprotective
      following ischemia and/or ischemia-reperfusion, as well as prevent the associated
      autonomic dysfunction. The selective ERalpha agonist, PPT, when administered 30
      min prior to occlusion of the middle cerebral artery (pMCAO), resulted in a dose
      dependent neuroprotection as measured 6 hours postpermanent MCAO, but not
      following 30 mins of MCAO followed by 5.5 hrs of reperfusion (I/R). In contrast,
      30 min pretreatment with the selective ERbeta agonist, DPN, resulted in a dose
      dependent neuroprotection following I/R, but was not protective following pMCAO.
      Both drugs prevented the ischemia-induced autonomic dysfunction as measured by a
      decrease in the baroreceptor reflex sensitivity (BRS). The data presented here
      suggest a differential role of each ER subtype in targeting the mechanisms of
      cell death that occur in ischemia versus reperfusion injury.

PMID- 21738529
TI  - Nonsurgical outpatient therapies for the management of female stress urinary
      incontinence: long-term effectiveness and durability.
AB  - Objective. To evaluate long-term effectiveness and safety of conservative and
      minimally invasive outpatient treatments for female stress urinary incontinence
      (SUI) through a review of the literature. Methods. PubMed was searched for
      reports on prospective clinical trials with at least 12-month follow-up of
      minimally invasive treatments, pelvic floor rehabilitation, or pharmacotherapy in
      women with SUI. Each report was examined for long-term rates of effectiveness and
      safety. Results. Thirty-two clinical trial reports were included. Prospective
      long-term studies of pelvic floor rehabilitation were limited but indicated
      significant improvements with treatment adherence for at least 12 months. Poor
      initial tolerability with duloxetine resulted in substantial discontinuation.
      Most patients receiving transurethral radiofrequency collagen denaturation or
      urethral bulking agents reported significant long-term improvements, generally
      good tolerability, and safety. Conclusions. Conservative therapy is an
      appropriate initial approach for female SUI, but if therapy fails, radiofrequency
      collagen denaturation or bulking agents may be an attractive intermediate
      management step or alternative to surgery.

PMID- 21738530
TI  - Clinical results of a brindley procedure: sacral anterior root stimulation in
      combination with a rhizotomy of the dorsal roots.
AB  - The Brindley procedure consists of a stimulator for sacral anterior-root
      stimulation and a rhizotomy of the dorsal sacral roots to abolish neurogenic
      detrusor overactivity. Stimulation of the sacral anterior roots enables
      micturition, defecation, and erections. This overview discusses the technique,
      selection of patients and clinical results of the Brindley procedure. The
      Brindley procedure is suitable for a selected group of patients with complete
      spinal cord injury and detrusor overactivity. Overall, the Brindley procedure
      shows good clinical results and improves quality of life. However, to remain a
      valuable treatment option for the future, the technique needs some adequate
      changes to enable analysis of the implanted parts, to improve revision techniques
      of the implanted parts, and to abolish the sacral dorsal rhizotomy.

PMID- 21738531
TI  - Predictors of clinical outcomes of flexible ureterorenoscopy with holmium laser
      for renal stone greater than 2 cm.
AB  - Objective. To evaluate the clinical outcome of flexible ureterorenoscopy (F-URS)
      with holmium laser in managing renal stone greater than 2 cm. Patients and
      Methods. Records of 120 patients (123 renal units) with renal stone greater than
      2 cm who underwent F-URS with holmium laser iwere evaluated. The mean stone size
      was 26.3 mm. Patient and stone characteristics, perioperative outcomes and
      complications were evaluated. The outcome was determined at 4 weeks on plain
      radiograph (KUB) and Non-contrast CT scan (NCCT). Follow-up visit was up to 6
      months to evaluate the clinical outcome and patients symptoms. Results. Stone
      burden was an independent predictor of FURS results. After first session of
      treatment, success rate was obtained in 72 renal units (58.5%). On the other
      hand, significant residual fragment was encountered in 51 renal units (41.5%).
      This was improved with "staged-therapy" to 87% and 96.7% after second and third
      session of treatment, respectively. Complications were recorded. They were
      managed in proper manner accordingly. Conclusion. This is an attractive, safe and
      effective technique. It is an ideal option for low volume complex stone with
      average burdens of 2 to 3 cm. Patient should be informed and consented about
      staged-therapy.

PMID- 21738532
TI  - Primary iliac venous leiomyosarcoma: a rare cause of deep vein thrombosis in a
      young patient.
AB  - Introduction. Primary venous tumours are a rare cause of deep vein thrombosis.
      The authors present a case where the definitive diagnosis was delayed by
      inconclusive complementary imaging. Clinical Case. A thirty-seven-year-old female
      presented with an iliofemoral venous thrombosis of the right lower limb. The
      patient had presented with an episode of femoral-popliteal vein thrombosis five
      months before and was currently under anticoagulation. Phlegmasia alba dolens
      installed progressively, as thrombus rapidly extended to the inferior vena cava
      despite systemic thrombolysis and anticoagulation. Diagnostic imaging failed to
      identify the underlying aetiology of the deep vein thrombosis. The definitive
      diagnosis of primary venous leiomyosarcoma was reached by a subcutaneous
      abdominal wall nodule biopsy. Conclusion. Primary venous leiomyosarcoma of the
      iliac vein is a rare cause of deep vein thrombosis, which must be considered in
      young patients with recurrent or refractory to treatment deep vein thrombosis.

PMID- 21738533
TI  - Left ventricular "diverticulum" in a patient affected by galactosialidosis.
AB  - We present the case of a 35-year-old man affected by the late juvenile form of
      galactosialidosis. He was known for a moderate pericardial effusion which
      remained unchanged in the last 12 months. Last follow-up transthoracic
      echocardiographic examination showed a bulging of the posterior and lateral wall
      of the left ventricle. This finding has never been described before in
      galactosialidosis.

PMID- 21738534
TI  - Primary omental torsion in an old woman: imaging techniques can prevent
      unnecessary surgical interventions.
AB  - Torsion and/or infarction of the greater omentum are rare but well-recognized
      clinical situations which present as an acute abdomen. The etiology is unknown
      and speculative. In most cases, the pathology is right sided and clinical
      presentation consists of an acute or subacute flank pain with mild peritonism
      usually evoking appendicitis or cholecystitis. Nevertheless, knowledge concerning
      these two problems can help the surgeon in proper diagnosis and treatment. Since
      the first report on primary torsion by Eitel in 1899, a few hundred more have
      been reported and some collective reviews published to date. Recently, ultra
      sonography and computed tomography have proved to provide sufficiently typical,
      consistent, and well-recognizable features to avoid unnecessary surgery. In this
      study, we will present a case diagnosed as primary omental torsion based on
      computed tomography, which underwent successful conservative management.

PMID- 21738535
TI  - Milk alkali and hydrochlorothiazide: a case report.
AB  - Hypercalcemia is a relatively common clinical problem in both outpatient and
      inpatient settings. Primary pathophysiology is the entry of calcium that exceeds
      its excretion into urine or deposition in bone into circulation. Among a wide
      array of causes of hypercalcemia, hyperparathyroidism and malignancy are the most
      common, accounting for greater than 90 percent of cases. Concordantly, there has
      been a resurgence of milk-alkali syndrome associated with the ingestion of large
      amounts of calcium and absorbable alkali, making it the third leading cause of
      hypercalcemia (Beall and Scofield, 1995 and Picolos et al., 2005). This paper
      centers on a case of over-the-counter calcium and alkali ingestion for acid
      reflux leading to milk alkali with concordant use of thiazide diuretic for
      hypertension.

PMID- 21738536
TI  - Primary colorectal adenocarcinoma metastatic to the breast: case report and
      review of nineteen cases.
AB  - Metastases to the breast from extramammary primaries are uncommon and account for
      0.5-6% of all breast malignancies (Georgiannos et al., 2001, and Vizcaino et al.,
      2001). Malignant melanoma, lymphoma, and lung and gastric carcinomas are the most
      frequently encountered nonmammary metastases to the breast in adults (Georgiannos
      et al., 2001, and Chaignaud et al., 1994). Primary colorectal adenocarcinoma
      (CRC) metastatic to the breast is extremely rare, with the medical literature
      having only 19 recorded cases. Typically CRC metastatic to the breast is
      indicative of widely disseminated disease and a poor prognosis. Here we present a
      case of poorly differentiated colon cancer metastatic to the breast and review
      the current literature on this rare event.

PMID- 21738537
TI  - Small cell ovarian cancer in adolescents: report of two cases and review of the
      literature.
AB  - Ovarian small cell carcinoma is a rare and highly malignant neoplasm carrying a
      poor prognosis. Although combination chemotherapy remains the cornerstone of
      treatment due to the rarity of these tumors, no regimen can be recommended as
      standard of care although in the majority of cases platinum-based regimens are
      used. Herein, we report two cases of small cell carcinoma of the ovaries along
      with a review of the relevant literature.

PMID- 21738538
TI  - Recent advances in the diagnosis and management of childhood acute promyelocytic
      leukemia.
AB  - Since the successful introduction of all-trans-retinoic acid (ATRA) and its
      combination with anthracycline-containing chemotherapy, the prognosis for acute
      promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline
      based-chemotherapy, the complete remission rate is greater than 90%, and the long
      term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was
      introduced for APL treatment in 1994, resulted in excellent remission rates in
      relapsed patients with APL, and more recently, several clinical studies have been
      designed to explore its role in initial therapy either alone or in combination
      with ATRA. APL is a rare disease in children and is frequently associated with
      hyperleukocytosis, which is a marker for higher risk of relapse and an increased
      incidence of microgranular morphology. The frequency of occurrence of the
      promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) isoforms bcr 2
      and bcr 3 is higher in children than in adults. Although recent clinical studies
      have reported comparable long-term survival rates in patients with APL, therapy
      for APL in children is challenging because of the risk of early death and the
      potential long-term cardiac toxicity resulting from the need to use high doses of
      anthracyclines. Additional prospective, randomized, large clinical trials are
      needed to address several issues in pediatric APL and to possibly minimize or
      eliminate the need for chemotherapy by combining ATRA and ATO. In this review
      article, we discuss the molecular pathogenesis, diagnostic progress, and most
      recent therapeutic advances in the treatment of children with APL.

PMID- 21738539
TI  - Philadelphia chromosome-positive acute lymphoblastic leukemia in childhood.
AB  - In pediatric patients with acute lymphoblastic leukemia (ALL), the Philadelphia
      chromosome translocation is uncommon, with a frequency of less than 5%. However,
      it is classified as a high or very high risk, and only 20-30% of Philadelphia
      chromosome-positive (Ph+) children with ALL are cured with chemotherapy alone.
      Allogeneic hematopoietic stem cell transplantation from a closely matched donor
      cures 60% of patients in first complete remission. Recent data suggest that
      chemotherapy plus tyrosine kinase inhibitors (TKIs) may be the initial treatment
      of choice for Ph+ ALL in children. However, longer observation is required to
      determine whether long-term outcome with intensive imatinib and chemotherapy is
      indeed equivalent to that with allogeneic related or alternative donor
      hematopoietic stem cell transplantation (HSCT). Reports on the use of second
      generation TKIs in children with Ph+ ALL are limited. A few case reports have
      indicated the feasibility and clinical benefit of using dasatinib as salvage
      therapy enabling HSCT. However, more extensive data from clinical trials are
      needed to determine whether the administration of second-generation TKIs in
      children is comparable to that in adults. Because Ph+ ALL is rare in children,
      the question of whether HSCT could be a dispensable part of their therapy may not
      be answered for some time. An international multicenter study is needed to answer
      the question of whether imatinib plus chemotherapy could replace sibling
      allogeneic HSCT in children with Ph+ ALL.

PMID- 21738540
TI  - The treatment of pediatric chronic myelogenous leukemia in the imatinib era.
AB  - Childhood chronic myelogenous leukemia (CML) is a rare hematologic disease, with
      limited literature on the methods of treatment. Previously, allogeneic
      hematopoietic stem cell transplantation (HSCT) was considered the only curative
      treatment for this disease. Treatment with imatinib, a selective inhibitor of the
      BCR-ABL tyrosine kinase (TKI), has resulted in prolonged molecular response with
      limited drug toxicity. Imatinib is now implemented in the primary treatment
      regimen for children, but the paucity of evidence on its ability to result in
      permanent cure and the potential complications that may arise from long-term
      treatment with TKIs have prevented imatinib from superseding HSCT as the primary
      means of curative treatment in children. The results of allogeneic HSCT in
      children with CML are similar to those observed in adults; HSCT-related
      complications such as transplant-related mortality and graft-versus-host disease
      remain significant challenges. An overall consensus has been formed with regards
      to the need for HSCT in patients with imatinib resistance or those with advanced
      phase disease. However, issues such as when to undertake HSCT in chronic-phase
      CML patients or how best to treat patients who have relapsed after HSCT are still
      controversial. The imatinib era calls for a reevaluation of the role of HSCT in
      the treatment of CML. Specific guidelines for the treatment of pediatric CML have
      not yet been formulated, underscoring the importance of prospective studies on
      issues such as duration of imatinib treatment, optimal timing of HSCT and the
      type of conditioning utilized, possible treatment pre- and post-HSCT, and the
      role of second-generation TKIs.

PMID- 21738541
TI  - Novel influenza A (H1N1) 2009 infection in the pediatric patients with
      hematologic and oncologic diseases in the Yeungnam region.
AB  - PURPOSE: Natural history and consequences of the novel 2009 influenza A H1N1
      (2009 H1N1) infection in immunocompromised pediatric patients are not yet fully
      understood. In this study, we investigated the clinical features and outcomes of
      the 2009 H1N1 infection in pediatric patients with hematological and oncological
      diseases. METHODS: We retrospectively reviewed the medical records of 528
      patients who had hematological and oncological diseases and who were treated at 7
      referral centers located in the Yeungnam region. Among the 528 patients, 27 with
      definite diagnosis of 2009 H1N1 infection were the subjects of this study. All
      patients were divided into the following 3 groups: patients who were receiving
      chemotherapy (group 1), patients who were immunosuppressed due to a non-malignant
      hematological disease (group 2), and patients who were off chemotherapy and had
      undergone their last chemotherapy course within 2 years from the influenza A
      pandemic (group 3). RESULTS: All 28 episodes of 2009 H1N1 infection were treated
      with the antiviral agent oseltamivir (Tamiflu(r)), and 20 episodes were treated
      after hospitalization. Group 1 patients had higher frequencies of lower
      respiratory tract infection and longer durations of fever and hospitalization as
      compared to those in group 2. Ultimately, all episodes resolved completely with
      no complications. CONCLUSION: These results suggest that early antiviral therapy
      did not influence the morbidity or mortality of pediatric patients with
      hematological and oncological diseases in the Yeungnam region of Korea after the
      2009 H1N1 infection. However, no definite conclusions can be drawn because of the
      small sample size.

PMID- 21738542
TI  - Mycoplasma pneumoniae infection in patients with Kawasaki disease.
AB  - PURPOSE: Kawasaki disease (KD) is the main cause of acquired heart disease in
      children. In addition to cardiovascular involvement, many complications have been
      recognized in KD. However, respiratory complications have been rarely reported.
      We investigated the differences in clinical characteristics, laboratory findings,
      radiography findings, and echocardiography findings of Mycoplasma pneumoniae
      infection and other types of pneumonia in KD patients. METHODS: Among 358
      patients with KD, 54 developed concurrent pneumonia. Among the 54 patients, 12
      (22.2%) with high titers of anti-M. pneumoniae antibody (AMA) (>1:640) were
      grouped in the M. pneumoniae group and 42 were included in the control group.
      Serum AMA was measured in each patient. Clinical laboratory findings and total
      duration of fever were analyzed. RESULTS: The duration of fever, serum
      hemoglobin, white blood cell count, platelet count, erythrocyte sedimentation
      rate, C-reactive protein level, albumin level, and the incidence of coronary
      arterial lesions showed no statistical difference in the 2 groups. Neutrophil
      count was significantly higher in the M. pneumoniae group than in the control
      group. Among various radiography findings observed in pneumonia, consolidation
      and pleural effusion were more frequent in the M. pneumoniae group than in the
      control group. On the other hand, parahilar peribronchial opacification, diffuse
      interstitial lesion, and normal findings prevailed in the control group.
      CONCLUSION: KD patients can have concurrent infections, especially pulmonary
      symptoms. The cause of KD is likely to be associated with M. pneumoniae
      infection. Thus, immediate treatment of M. pneumoniae infection in KD patients is
      very important.

PMID- 21738543
TI  - Responses and adverse effects of carboplatin-based chemotherapy for pediatric
      intracranial germ cell tumors.
AB  - PURPOSE: Cisplatin-based chemotherapy has been commonly used for the treatment of
      intracranial germ cell tumors (IC-GCTs). However, this treatment exhibits some
      adverse effects such as renal problems and hearing difficulty. Carboplatin-based
      chemotherapy was administered to pediatric patients with IC-GCTs from August 2004
      at the Samsung Medical Center. In this study, we assessed the responses and
      adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients
      according to the risk group, and compared the results with those of the previous
      cisplatin-based chemotherapy. METHODS: We examined 35 patients (27 men and 8
      women) diagnosed with IC-GCTs between August 2004 and April 2008 and received
      risk-adapted carboplatin-based chemotherapy at the Samsung Medical Center.
      Patients were divided into either low-risk (LR) or high-risk (HR) groups and a
      retrospective analysis was performed using information from the medical records.
      RESULTS: Although hematological complications were common, hearing difficulties
      or grade 3 or 4 creatinine level elevation were not observed in patients who
      underwent carboplatin-based chemotherapy. The frequency of febrile neutropenia
      did not differ between the risk groups. The overall survival was 100% and event
      free survival (EFS) was 95.7%. The EFS rate was 100% in the LR group and 90% in
      the HR group, respectively. CONCLUSION: Despite their common occurrence in high
      risk patients, no lethal hematological complications were associated with
      carboplatin-based treatment. The current carboplatin-based chemotherapy protocol
      is safe and effective for the treatment of pediatric patients with IC-GCTs.

PMID- 21738544
TI  - Misdiagnosis of fetus-in-fetu as meconium peritonitis.
AB  - Fetus-in-fetu (FIF) is a rare congenital condition in which a fetiform mass is
      detected in the host abdomen and also in other sites such as the intracranium,
      thorax, head, and neck. This condition has been rarely reported in the
      literature. Herein, we report the case of a fetus presenting with abdominal
      cystic mass and ascites and prenatally diagnosed as meconium pseudocyst.
      Explorative laparotomy revealed an irregular fetiform mass in the retroperitoneum
      within a fluid-filled cyst. The mass contained intestinal tract, liver, pancreas,
      and finger. Fetal abdominal cystic mass has been identified in a broad spectrum
      of diseases. However, as in our case, FIF is often overlooked during differential
      diagnosis. FIF should also be differentiated from other conditions associated
      with fetal abdominal masses.

PMID- 21738545
TI  - Testicular adrenal rest tumors in a patient with untreated congenital adrenal
      hyperplasia.
AB  - Testicular adrenal rest tumors (TARTs) are considered to be formed from aberrant
      adrenal tissue that has become hyperplastic because of elevated
      adrenocorticotropic hormone (ACTH) in male patients with congenital adrenal
      hyperplasia (CAH). A 6-year-old boy presented with testicular enlargement and
      pubic hair. He was diagnosed with CAH complicated by precocious puberty. However,
      he was not followed-up. At the age of 17, he visited the outpatient clinic
      because of testicular enlargement and short stature. His right and left testicles
      were 10*6 cm and 7.5*4.5 cm, respectively. His height was 155.1 cm (standard
      deviation score [SDS], -2.90). The diagnosis of CAH due to 21 hydroxylase
      deficiency was confirmed by mutation analysis of CYP21A2. Histological
      examination of the testes showed large, polygonal, eosinophilic cells with round
      nuclei and prominent nucleoli, which were suggestive of TARTs. He was treated
      with dexamethasone for 3 weeks and tumors regressed. Subsequently, dexamethasone
      was replaced by prednisolone and 9alpha-fludrocortisone; thereafter, the reduced
      testis size has been maintained.

PMID- 21738546
TI  - Recommendation for the use of newly introduced Tdap vaccine in Korea.
AB  - Pertussis is an acute respiratory infection characterized by paroxysmal cough and
      inspiratory whoop for over 2 weeks. The incidence of pertussis has decreased
      markedly after the introduction of DTwP/DTaP vaccine, but the incidence of
      pertussis has increased steadily among young infant and among adolescents and
      adults in many countries. Td vaccine was used in this age group but the increase
      in pertussis has lead to the development of a Tdap vaccine. The Tdap vaccine is a
      Td vaccine with a pertussis vaccine added and is thought to decrease the
      incidence and transmission of pertussis in the respective age group. In Korea,
      two products are approved by the KOREA FOOD & DRUG ADMINISTRATION, which are
      ADACELTM (Sanofi-Pasteur, Totonto, Ontario, Canada) and BOOSTRIX(r)
      (GlaxoSmithKline Biologicals, Rixensart, Belgium) for those aged between 11-64.
      This report summarizes the recommendations approved by the Committee on
      Infectious Diseases, the Korean Pediatric Society.

PMID- 21738547
TI  - Recommendation for use of the newly introduced pneumococcal protein conjugate
      vaccines in Korea.
AB  - Streptococcus pneumoniae remains a leading cause of invasive infections including
      bacteremia and meningitis, as well as mucosal infections such as otitis media and
      pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine
      (PCV7) was licensed for use among infants and young children in many countries
      including Korea. The routine use of PCV7 has resulted in a decreased incidence of
      invasive pneumococcal disease (IPD) by the vaccine serotypes among the vaccinees
      and substantial declines in IPD among unvaccinated populations such as older
      children and adults as well. In addition, there are increasing evidences to
      suggest that routine immunization with PCV7 is changing the epidemiology of
      pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal
      colonization, and antibiotic resistance patterns. In contrast, there is an
      increase in the number of IPDs caused by nonvaccine serotypes, though it is much
      smaller than overall declines of vaccine serotype diseases. Several vaccines
      containing additional serotypes have been developed and tested clinically in
      order to expand the range of serotypes of Streptococcus pneumoniae. Recently two
      new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate
      vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13), have been
      approved for use in several countries including Korea. This report summarizes the
      recommendations approved by the Committee on Infectious Diseases, the Korean
      Pediatric Society.

PMID- 21738548
TI  - Impact factor of Korean Journal of Pediatrics on Korean Medical Citation Index
      and Science Citation Index of Web of Science.
AB  - PURPOSE: The total number of times a paper is cited, also known as the impact
      factor (IF) of a medical journal, is widely implied in evaluating the quality of
      a research paper. We evaluated the citation index data as an IF of Korean J
      Pediatr in Korean Medical Citation Index (KoMCI) and JCI of Web of Science.
      METHODS: We calculated the IF of Korean J Pediatr at KoMCI supervised by Korean
      Association of Medical Journal Editors. And we estimated the IF of Korean J
      Pediatr by the JCI of Web of Science although it was never officially reported.
      RESULTS: The IF of Korean J Pediatr on KoMCI has increased from 0.100 in the year
      2000, to 0.205 in 2008, and 0.326 in 2009. Although the IF of Korean J Pediatr
      was 0.006 in 2005, 0.018 in 2006, 0.028 in 2008, 0.066 in 2009, and 0.018 in 2010
      according to the JCI of Web of Science, the number of citations are steadily
      increasing. CONCLUSION: Understanding and realizing the current status will be a
      stepping stone for further improvement. The next objective of the Korean J
      Pediatr is to become registered in the SCI or SCIE. Increasing the IF according
      to the JCI of Web of Science is crucial in order to achieve this goal.

PMID- 21738549
TI  - Alteration of CD4CD25Foxp3 T cell level in Kawasaki disease.
AB  - PURPOSE: Exaggerated pro-inflammatory reactions during the acute phase of
      Kawasaki disease (KD) suggest the role of immune dysregulation in the
      pathogenesis of KD. We investigated the profiles of T regulatory cells and their
      correlation with the clinical course of KD. METHODS: Peripheral blood mononuclear
      cells were collected from 17 KD patients during acute febrile and subacute
      afebrile phases. T cells expressing CD4, CD25, and Foxp3 were analyzed using flow
      cytometry, and the results were correlated with the clinical course of KD.
      RESULTS: The percentage of circulating CD4(+)CD25(high)Foxp3(+) T cells among
      CD4(+) T cells was significantly higher during the subacute afebrile phase than
      during the acute febrile phase (1.10%+/-1.22% vs. 0.55%+/-0.53%, P=0.049).
      Although levels of CD4(+)CD25(low)Foxp3(+) T cells and CD4(+)CD25(-)Foxp3(+) T
      cells were only slightly altered, the percentage of CD4(+)CD25(+)Foxp3(-) T cells
      among CD4(+) T cells was significantly lower during the subacute afebrile phase
      than during the acute febrile phase (2.96%+/-1.95% vs. 5.64%+/-5.69%, P=0.036).
      Consequently, the ratio of CD25(high)Foxp3(+) T cells to CD25(+)Foxp3(-) T cells
      was higher during the subacute afebrile phase than during the acute febrile phase
      (0.45%+/-0.57% vs. 0.13%+/-0.13%, P=0.038). CONCLUSION: Decreased
      CD4(+)CD25(high)Foxp3(+) T cells and/or an imbalanced ratio of
      CD4(+)CD25(high)Foxp3(+) T cells to CD4(+)CD25(+)Foxp3(-) T cells might play a
      role in KD development. Considering that all KD patients were treated with
      intravenous immunoglobulin (IVIG), recovery of CD4(+)CD25(high)Foxp3(+) T cells
      during the subacute afebrile phase could be a mechanism of IVIG.

PMID- 21738550
TI  - Immune response to 19A serotype after immunization of 19F containing pneumococcal
      conjugate vaccine in Korean children aged 12-23 months.
AB  - PURPOSE: The purpose of this study was to evaluate the immune response to
      serotype 19A in children aged 12-23 months after immunization of the 19F
      containing 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Blood samples
      from a total of 45 subjects (age 12-23 months) were included in the study.
      Subjects were categorized according to immunization status into three groups as
      follows: 18 subjects with 3 primary doses and 1 booster dose of PCV7 (booster
      group), 21 subjects with 3 primary doses before 12 months of age (primary group),
      and 6 subjects with no vaccination history of PCV7 (control group). An ELISA and
      opsonophagocytic killing assay (OPKA) was done to evaluate the immune responses
      against serotypes 19F and 19A. RESULTS: According to the ELISA, all subjects had
      antibody titers >=0.35 ug/mL for serotypes 19F and 19A in the booster and primary
      group and 83.0% and 66.7% in the control group, respectively. According to the
      OPKA, subjects with opsonic activity (>=20) against serotypes 19F and 19A were
      100% and 61.1% of the subjects in the booster group and 66.7% and 19.0% in the
      primary group, respectively. No subjects in the control group had opsonic
      antibodies against both serotypes. CONCLUSION: In conclusion, in children 12-23
      months age who were previously vaccinated with PCV7, a cross-reactive immune
      response is elicited against serotype 19A after a primary series of 3 doses in a
      small proportion of subjects, and this response is amplified after booster
      vaccination.

PMID- 21738551
TI  - Selective embolization of the internal iliac arteries for the treatment of
      intractable hemorrhage in children with malignancies.
AB  - PURPOSE: Acute internal hemorrhage is an occasionally life-threatening
      complication in pediatric cancer patients. Many therapeutic approaches have been
      used to control bleeding with various degrees of success. In this study, we
      evaluated the efficacy of selective internal iliac artery embolization for
      controlling acute intractable bleeding in children with malignancies. METHODS: We
      retrospectively evaluated the cases of 6 children with various malignancies
      (acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous
      leukemia, T-cell prolymphocytic leukemia, Langerhans cell histiocytosis, and
      rhabdomyosarcoma), who had undergone selective arterial embolization (SAE) of the
      internal iliac artery at the Chonnam National University Hwasun Hospital between
      January 2004 and December 2009. SAE was performed by an interventional
      radiologist using Gelfoam(r) and/or Tornado(r) coils. RESULTS: The patients were
      5 boys and 1 girl with median age of 6.9 years (range, 0.7-14.8 years) at the
      time of SAE. SAE was performed once in 4 patients and twice in 2, and the
      procedure was unilateral in 2 and bilateral in 4. The causes of hemorrhage were
      as follows: hemorrhagic cystitis (HC) in 3 patients, procedure-related internal
      iliac artery injuries in 2 patients, and tumor rupture in 1 patient. Initial
      attempt at conservative management was unsuccessful. Of the 6 patients, 5 (83.3%)
      showed improvement after SAE without complications. CONCLUSION: SAE may be a safe
      and effective procedure for controlling acute intractable hemorrhage in pediatric
      malignancy patients. This procedure may obviate the need for surgery, which
      carries an attendant risk of morbidity and mortality in cancer patients with
      critical conditions.

PMID- 21738552
TI  - A case of hemolytic uremic syndrome preceded by intussusception.
AB  - Hemolytic-uremic syndrome (HUS) is the most common cause of acute renal failure
      in young children. It is classically characterized by the triad of
      microangiopathic hemolytic anemia, thrombocytopenia, and uremia. Further, not
      only is intussusception one of the differential diagnoses of HUS but it may also
      become a complication during disease progression. We report a case of HUS
      preceded by intussusception in a previously healthy 17-month-old boy. The patient
      presented at the emergency department with bloody stools that developed the day
      after reduction of intussusception. HUS was diagnosed 4 days after the reduction
      of intussusception. The patient was provided only supportive care and his
      laboratory test findings were normal at discharge.

PMID- 21738553
TI  - Transient neonatal diabetes mellitus caused by a de novoABCC8 gene mutation.
AB  - Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus
      that presents within the first 6 months of life with remission in infancy or
      early childhood. TNDM is mainly caused by anomalies in the imprinted region on
      chromosome 6q24; however, recently, mutations in the ABCC8 gene, which encodes
      sulfonylurea receptor 1 (SUR1), have also been implicated in TNDM. Herein, we
      present the case of a male child with TNDM whose mutational analysis revealed a
      heterozygous c.3547C>T substitution in the ABCC8 gene, leading to an Arg1183Trp
      mutation in the SUR1 protein. The parents were clinically unaffected and did not
      show a mutation in the ABCC8 gene. This is the first case of a de novoABCC8 gene
      mutation in a Korean patient with TNDM. The patient was initially treated with
      insulin and successfully switched to sulfonylurea therapy at 14 months of age.
      Remission of diabetes had occurred at the age of 16 months. Currently, the
      patient is 21 months old and is euglycemic without any insulin or oral
      hypoglycemic agents. His growth and physical development are normal, and there
      are no delays in achieving neurological and developmental milestones.

PMID- 21738554
TI  - Development of Randomly Amplified Polymorphic DNA Based SCAR Marker for
      Identification of Ipomoea mauritiana Jacq (Convolvulaceae).
AB  - Vidari is an Ayurvedic herbal drug used as aphrodisiac, galactagogue and is also
      used in the preparation of Chyavanaprash. Tubers of Ipomoea mauritiana Jacq.
      (Convolvulaceae), Pueraria tuberosa (Roxb. ex Willd.) DC (Fabaceae), Adenia
      hondala (Gaertn.) de Wilde (Passifloraceae) and pith of Cycas circinalis L.
      (Cycadaceae) are all traded in the name of Vidari, creating issues of botanical
      authenticity of the Ayurvedic raw drug. DNA-based markers have been developed to
      distinguish I. mauritiana from the other Vidari candidates. A putative 600-bp
      polymorphic sequence, specific to I. mauritiana was identified using randomly
      amplified polymorphic DNA (RAPD) technique. Furthermore, sequence characterized
      amplified region (SCAR) primers (IM1F and IM1R) were designed from the unique
      RAPD amplicon. The SCAR primers produced a specific 323-bp amplicon in authentic
      I. mauritiana and not in the allied species.

PMID- 21738555
TI  - Ethanol Extract from Ampelopsis sinica Root Exerts Anti-Hepatitis B Virus
      Activity via Inhibition of p53 Pathway In Vitro.
AB  - Ampelopsis sinica root is widely used in Chinese folk medicine for treating liver
      disorders caused by the hepatitis B virus (HBV). The present study was performed
      in order to investigate the anti-HBV activity and mechanisms of the ethanol
      extract from A. sinica root (EASR) in vitro. The antiviral activity of EASR was
      examined by detecting the levels of HBsAg, HBeAg and extracellular HBV DNAs in
      stable HBV-producing human hepatoblastoma HepG2 2.2.15 cells. We found that EASR
      effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells
      in a dose-dependent manner, and it also suppressed the amount of extracellular
      HBV DNA. After EASR treatment, the percentage of apoptotic cells was found to be
      significantly higher than that of control by flow cytometric analysis. A
      luciferase reporter gene assay was used to determine the effects of EASR on the
      activities of HBV promoters and intracellular signaling pathways. The results
      showed that EASR selectively inhibited the activities of HBV promoters (Cp, S1p
      and Fp) and the p53 signaling pathway in HepG2 cells significantly. These data
      indicate that EASR exerts anti-HBV effects via inhibition of HBV promoters and
      the p53-associated signaling pathway, which helps to elucidate the mechanism
      underlying the potential therapeutic value of EASR.

PMID- 21738556
TI  - Understanding the Early Origins of the Education-Health Gradient: A Framework
      That Can Also Be Applied to Analyze Gene-Environment Interactions.
AB  - In this article, we develop a framework for analyzing the causal effects of
      interventions in the presence of latent factors that could affect outcomes, even
      in the absence of interventions. This framework will be useful in situations in
      which genes are included among the latent factors. We estimate the model and
      study the early origins of observed later-life disparities by education. We
      determine the role played by cognitive, noncognitive, and early health
      endowments. We identify the causal effect of education on health and health
      related behaviors. We show that family background characteristics and cognitive,
      noncognitive, and health endowments developed by age 10 are important
      determinants of health disparities at age 30. We also show that not properly
      accounting for personality traits results in overestimation of the importance of
      cognitive ability in determining later health. Selection on preexisting traits
      explains more than half of the observed differences in poor health and obesity.
      Education has an important causal effect in explaining differences in smoking
      rates. There are significant gender differences. We go beyond the current
      literature, which typically estimates mean effects, to compute distributions of
      treatment effects. We show that the effect of education on health varies among
      individuals who are similar in their observed characteristics, and how a mean
      effect can hide gains and losses for different individuals. This analysis
      highlights the crucial role played by promotion of good health at an early age
      and the importance of prevention in the reduction of health disparities. We
      speculate about how the model can be applied to genetic studies. 

PMID- 21738558
TI  - Do extraverts process social stimuli differently from introverts?
AB  - The personality trait of extraversion has been linked to the network of brain
      systems controlling sensitivity to cues of reward and generating approach
      behavior in response, but little is known about whether extraverts' neural
      circuits are especially sensitive to social stimuli, given their preference for
      social engagement. Utilizing event-related potential (ERP) methodology, this
      study demonstrates that variation on the extraversion dimension is associated
      with the extent to which social stimuli evoke enhanced allocation of attention.
      Specifically, higher scores on extraversion were found to be associated with
      higher amplitudes of the P300 component of the ERPs elicited by human faces. This
      finding suggests that social stimuli carry enhanced motivational significance for
      individuals characterized by high extraversion, and that individual differences
      in personality are related to meaningful individual differences in neural
      responses to social stimuli.

PMID- 21738557
TI  - Implications of the innate immune response to adenovirus and adenoviral vectors.
AB  - Adenovirus (AdV) is a common cause of respiratory illness in both children and
      adults. Respiratory symptoms can range from those of the common cold to severe
      pneumonia. Infection can also cause significant disease in the immunocompromised
      and among immunocompetent subjects in close quarters. Fortunately, infection with
      AdV in the normal host is generally mild. This is one reason why its initial use
      as a gene-therapy vector appeared to be so promising. Unfortunately, both innate
      and adaptive responses to the virus have limited the development of AdV vectors
      as a tool of gene therapy by increasing toxicity and limiting duration of
      transgene expression. This article will focus on the innate immune response to
      infection with wild-type AdV and exposure to AdV gene-therapy vectors. As much of
      the known information relates to the pulmonary inflammatory response, this organ
      system will be emphasized. This article will also discuss how that understanding
      has led to the creation of new vectors for use in gene therapy.

PMID- 21738559
TI  - Hybrid Steered Molecular Dynamics-Docking: An Efficient Solution to the Problem
      of Ranking Inhibitor Affinities Against a Flexible Drug Target.
AB  - Existing techniques which attempt to predict the affinity of protein-ligand
      interactions have demonstrated a direct relationship between computational cost
      and prediction accuracy. We present here the first application of a hybrid
      ensemble docking and steered molecular dynamics scheme (with a minimized
      computational cost), which achieves a binding affinity rank-ordering of ligands
      with a Spearman correlation coefficient of 0.79 and an RMS error of 0.7 kcal/mol.
      The scheme, termed Flexible Enzyme Receptor Method by Steered Molecular Dynamics
      (FERM-SMD), is applied to an in-house collection of 17 validated ligands of
      glutamate racemase. The resulting improved accuracy in affinity prediction allows
      elucidation of the key structural components of a heretofore unreported glutamate
      racemase inhibitor (K(i) = 9 uM), a promising new lead in the development of
      antibacterial therapeutics.

PMID- 21738560
TI  - Subconjunctival Dirofilaria repens Infestation: A Light and Scanning Electron
      Microscopy Study.
AB  - BACKGROUND: To present a case of subconjunctival infestation with Dirofilaria
      repens which is very rare in Northern Europe. METHODS: A 61-year-old male
      presented with a swelling and redness of the left supraorbital region migrating
      to the eyelid and the left eyeball resulting in conjunctival injection, proptosis
      and diplopia. The patient underwent incisional extraction of a nine cm long worm,
      which was analysed histologically. RESULTS: The worm was structureless, greyish
      white in colour and measuring nine cm in length and 0.5 mm in diameter.
      Histopathological examination of the worm showed an outer thick, multi-layered
      cuticle with longitudinal ridges. Beneath the cuticle, a thick muscle layer was
      observed and internally the intestine and a single reproductive tube containing
      spermatozoa were noted. Scanning electron microscopy of the worm showed tapered
      ends, transverse striations and longitudinal ridges at the anterior end. The tail
      was relatively short with spirally coiled ridges indicating a male Dirofilaria
      repens. CONCLUSIONS: Humans are an uncommon and accidental host of Dirofilaria
      repens which is rarely seen in Northern Europe but should be considered as a
      differential diagnosis to other nematode ocular infections. A travel history is
      helpful in diagnosing the potential involved organisms. No further treatment is
      necessary beyond surgical removal since this organism fails to mature and thereby
      does not cause microfilariaemia in humans.

PMID- 21738561
TI  - Dansyl - Substituted Aza Crown Ethers: Complexation with Alkali, Alkaline Earth
      Metal Ions and Ammonium.
AB  - The present study investigates the binding properties of four dansyl substituted
      aza-crown ethers with alkali, alkaline earth metal ions and ammonium. The
      influence of the solvent polarity and protonation on the photophysical properties
      of the compounds was studied by UV/Vis and fluorescence methods. The host species
      caused only slight changes on the absorption spectra of the ligands. The
      fluorescence changes were more pronounced and concentration dependent thus
      allowing to calculate the binding constants of the process. The most stable
      complex under our working conditions was the one between Ba(2+) and DNS18C6.

PMID- 21738567
TI  - The pH dependence of polymerization and bundling by the essential bacterial
      cytoskeletal protein FtsZ.
AB  - There is a growing body of evidence that bacterial cell division is an intricate
      coordinated process of comparable complexity to that seen in eukaryotic cells.
      The dynamic assembly of Escherichia coli FtsZ in the presence of GTP is
      fundamental to its activity. FtsZ polymerization is a very attractive target for
      novel antibiotics given its fundamental and universal function. In this study our
      aim was to understand further the GTP-dependent FtsZ polymerization mechanism and
      our main focus is on the pH dependence of its behaviour. A key feature of this
      work is the use of linear dichroism (LD) to follow the polymerization of FtsZ
      monomers into polymeric structures. LD is the differential absorption of light
      polarized parallel and perpendicular to an orientation direction (in this case
      that provided by shear flow). It thus readily distinguishes between FtsZ polymers
      and monomers. It also distinguishes FtsZ polymers and less well-defined
      aggregates, which light scattering methodologies do not. The polymerization of
      FtsZ over a range of pHs was studied by right-angled light scattering to probe
      mass of FtsZ structures, LD to probe real-time formation of linear polymeric
      fibres, a specially developed phosphate release assay to relate guanosine
      triphosphate (GTP) hydrolysis to polymer formation, and electron microscopy (EM)
      imaging of reaction products as a function of time and pH. We have found that
      lowering the pH from neutral to 6.5 does not change the nature of the FtsZ
      polymers in solution--it simply facilitates the polymerization so the fibres
      present are longer and more abundant. Conversely, lowering the pH to 6.0 has much
      the same effect as introducing divalent cations or the FtsZ-associated protein
      YgfE (a putative ZapA orthologue in E. coli)--it stabilizes associations of
      protofilaments.

PMID- 21738568
TI  - Comparative structural analysis of lipid binding START domains.
AB  - BACKGROUND: Steroidogenic acute regulatory (StAR) protein related lipid transfer
      (START) domains are small globular modules that form a cavity where lipids and
      lipid hormones bind. These domains can transport ligands to facilitate lipid
      exchange between biological membranes, and they have been postulated to modulate
      the activity of other domains of the protein in response to ligand binding. More
      than a dozen human genes encode START domains, and several of them are implicated
      in a disease. PRINCIPAL FINDINGS: We report crystal structures of the human
      STARD1, STARD5, STARD13 and STARD14 lipid transfer domains. These represent four
      of the six functional classes of START domains. SIGNIFICANCE: Sequence alignments
      based on these and previously reported crystal structures define the structural
      determinants of human START domains, both those related to structural framework
      and those involved in ligand specificity. ENHANCED VERSION: This article can also
      be viewed as an enhanced version in which the text of the article is integrated
      with interactive 3D representations and animated transitions. Please note that a
      web plugin is required to access this enhanced functionality. Instructions for
      the installation and use of the web plugin are available in Text S1.

PMID- 21738569
TI  - Visualization of early events in acetic acid denaturation of HIV-1 protease: a
      molecular dynamics study.
AB  - Protein denaturation plays a crucial role in cellular processes. In this study,
      denaturation of HIV-1 Protease (PR) was investigated by all-atom MD simulations
      in explicit solvent. The PR dimer and monomer were simulated separately in 9 M
      acetic acid (9 M AcOH) solution and water to study the denaturation process of PR
      in acetic acid environment. Direct visualization of the denaturation dynamics
      that is readily available from such simulations has been presented. Our
      simulations in 9 M AcOH reveal that the PR denaturation begins by separation of
      dimer into intact monomers and it is only after this separation that the monomer
      units start denaturing. The denaturation of the monomers is flagged off by the
      loss of crucial interactions between the alpha-helix at C-terminal and
      surrounding beta-strands. This causes the structure to transit from the
      equilibrium dynamics to random non-equilibrating dynamics. Residence time
      calculations indicate that denaturation occurs via direct interaction of the
      acetic acid molecules with certain regions of the protein in 9 M AcOH. All these
      observations have helped to decipher a picture of the early events in acetic acid
      denaturation of PR and have illustrated that the alpha-helix and the beta-sheet
      at the C-terminus of a native and functional PR dimer should maintain both the
      stability and the function of the enzyme and thus present newer targets for
      blocking PR function.

PMID- 21738570
TI  - From SNPs to genes: disease association at the gene level.
AB  - Interpreting Genome-Wide Association Studies (GWAS) at a gene level is an
      important step towards understanding the molecular processes that lead to
      disease. In order to incorporate prior biological knowledge such as pathways and
      protein interactions in the analysis of GWAS data it is necessary to derive one
      measure of association for each gene. We compare three different methods to
      obtain gene-wide test statistics from Single Nucleotide Polymorphism (SNP) based
      association data: choosing the test statistic from the most significant SNP; the
      mean test statistics of all SNPs; and the mean of the top quartile of all test
      statistics. We demonstrate that the gene-wide test statistics can be controlled
      for the number of SNPs within each gene and show that all three methods perform
      considerably better than expected by chance at identifying genes with confirmed
      associations. By applying each method to GWAS data for Crohn's Disease and Type 1
      Diabetes we identified new potential disease genes.

PMID- 21738571
TI  - Systemic analysis of heat shock response induced by heat shock and a proteasome
      inhibitor MG132.
AB  - The molecular basis of heat shock response (HSR), a cellular defense mechanism
      against various stresses, is not well understood. In this, the first
      comprehensive analysis of gene expression changes in response to heat shock and
      MG132 (a proteasome inhibitor), both of which are known to induce heat shock
      proteins (Hsps), we compared the responses of normal mouse fibrosarcoma cell
      line, RIF-1, and its thermotolerant variant cell line, TR-RIF-1 (TR), to the two
      stresses. The cellular responses we examined included Hsp expressions, cell
      viability, total protein synthesis patterns, and accumulation of poly
      ubiquitinated proteins. We also compared the mRNA expression profiles and
      kinetics, in the two cell lines exposed to the two stresses, using microarray
      analysis. In contrast to RIF-1 cells, TR cells resist heat shock caused changes
      in cell viability and whole-cell protein synthesis. The patterns of total
      cellular protein synthesis and accumulation of poly-ubiquitinated proteins in the
      two cell lines were distinct, depending on the stress and the cell line.
      Microarray analysis revealed that the gene expression pattern of TR cells was
      faster and more transient than that of RIF-1 cells, in response to heat shock,
      while both RIF-1 and TR cells showed similar kinetics of mRNA expression in
      response to MG132. We also found that 2,208 genes were up-regulated more than 2
      fold and could sort them into three groups: 1) genes regulated by both heat shock
      and MG132, (e.g. chaperones); 2) those regulated only by heat shock (e.g. DNA
      binding proteins including histones); and 3) those regulated only by MG132 (e.g.
      innate immunity and defense related molecules). This study shows that heat shock
      and MG132 share some aspects of HSR signaling pathway, at the same time, inducing
      distinct stress response signaling pathways, triggered by distinct abnormal
      proteins.

PMID- 21738572
TI  - Designing nanoconjugates to effectively target pancreatic cancer cells in vitro
      and in vivo.
AB  - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related
      deaths in America. Monoclonal antibodies are a viable treatment option for
      inhibiting cancer growth. Tumor specific drug delivery could be achieved
      utilizing these monoclonal antibodies as targeting agents. This type of designer
      therapeutic is evolving and with the use of gold nanoparticles it is a promising
      approach to selectively deliver chemotherapeutics to malignant cells. Gold
      nanoparticles (GNPs) are showing extreme promise in current medicinal research.
      GNPs have been shown to non-invasively kill tumor cells by hyperthermia using
      radiofrequency. They have also been implemented as early detection agents due to
      their unique X-ray contrast properties; success was revealed with clear
      delineation of blood capillaries in a preclinical model by CT (computer
      tomography). The fundamental parameters for intelligent design of nanoconjugates
      are on the forefront. The goal of this study is to define the necessary design
      parameters to successfully target pancreatic cancer cells. METHODOLOGY/PRINCIPAL
      FINDINGS: The nanoconjugates described in this study were characterized with
      various physico-chemical techniques. We demonstrate that the number of cetuximab
      molecules (targeting agent) on a GNP, the hydrodynamic size of the
      nanoconjugates, available reactive surface area and the ability of the
      nanoconjugates to sequester EGFR (epidermal growth factor receptor), all play
      critical roles in effectively targeting tumor cells in vitro and in vivo in an
      orthotopic model of pancreatic cancer. CONCLUSION: Our results suggest the
      specific targeting of tumor cells depends on a number of crucial components 1)
      targeting agent to nanoparticle ratio 2) availability of reactive surface area on
      the nanoparticle 3) ability of the nanoconjugate to bind the target and 4)
      hydrodynamic diameter of the nanoconjugate. We believe this study will help
      define the design parameters for formulating better strategies for specifically
      targeting tumors with nanoparticle conjugates.

PMID- 21738573
TI  - Time to evolve? Potential evolutionary responses of fraser river sockeye salmon
      to climate change and effects on persistence.
AB  - Evolutionary adaptation affects demographic resilience to climate change but few
      studies have attempted to project changes in selective pressures or quantify
      impacts of trait responses on population dynamics and extinction risk. We used a
      novel individual-based model to explore potential evolutionary changes in
      migration timing and the consequences for population persistence in sockeye
      salmon Oncorhynchus nerka in the Fraser River, Canada, under scenarios of future
      climate warming. Adult sockeye salmon are highly sensitive to increases in water
      temperature during their arduous upriver migration, raising concerns about the
      fate of these ecologically, culturally, and commercially important fish in a
      warmer future. Our results suggest that evolution of upriver migration timing
      could allow these salmon to avoid increasingly frequent stressful temperatures,
      with the odds of population persistence increasing in proportion to the trait
      heritability and phenotypic variance. With a simulated 2 degrees C increase in
      average summer river temperatures by 2100, adult migration timing from the ocean
      to the river advanced by ~10 days when the heritability was 0.5, while the risk
      of quasi-extinction was only 17% of that faced by populations with zero
      evolutionary potential (i.e., heritability fixed at zero). The rates of evolution
      required to maintain persistence under simulated scenarios of moderate to rapid
      warming are plausible based on estimated heritabilities and rates of
      microevolution of timing traits in salmon and related species, although further
      empirical work is required to assess potential genetic and ecophysiological
      constraints on phenological adaptation. These results highlight the benefits to
      salmon management of maintaining evolutionary potential within populations, in
      addition to conserving key habitats and minimizing additional stressors where
      possible, as a means to build resilience to ongoing climate change. More
      generally, they demonstrate the importance and feasibility of considering
      evolutionary processes, in addition to ecology and demography, when projecting
      population responses to environmental change.

PMID- 21738574
TI  - Proteomic analysis of pathways involved in estrogen-induced growth and apoptosis
      of breast cancer cells.
AB  - BACKGROUND: Estrogen is a known growth promoter for estrogen receptor (ER)
      positive breast cancer cells. Paradoxically, in breast cancer cells that have
      been chronically deprived of estrogen stimulation, re-introduction of the hormone
      can induce apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Here, we sought to identify
      signaling networks that are triggered by estradiol (E2) in isogenic MCF-7 breast
      cancer cells that undergo apoptosis (MCF-7:5C) versus cells that proliferate upon
      exposure to E2 (MCF-7). The nuclear receptor co-activator AIB1 (Amplified in
      Breast Cancer-1) is known to be rate-limiting for E2-induced cell survival
      responses in MCF-7 cells and was found here to also be required for the induction
      of apoptosis by E2 in the MCF-7:5C cells. Proteins that interact with AIB1 as
      well as complexes that contain tyrosine phosphorylated proteins were isolated by
      immunoprecipitation and identified by mass spectrometry (MS) at baseline and
      after a brief exposure to E2 for two hours. Bioinformatic network analyses of the
      identified protein interactions were then used to analyze E2 signaling pathways
      that trigger apoptosis versus survival. Comparison of MS data with a
      computationally-predicted AIB1 interaction network showed that 26 proteins
      identified in this study are within this network, and are involved in signal
      transduction, transcription, cell cycle regulation and protein degradation.
      CONCLUSIONS: G-protein-coupled receptors, PI3 kinase, Wnt and Notch signaling
      pathways were most strongly associated with E2-induced proliferation or apoptosis
      and are integrated here into a global AIB1 signaling network that controls
      qualitatively distinct responses to estrogen.

PMID- 21738575
TI  - Rapid and accurate detection of Mycobacterium tuberculosis in sputum samples by
      Cepheid Xpert MTB/RIF assay--a clinical validation study.
AB  - BACKGROUND: A crucial impediment to global tuberculosis control is the lack of an
      accurate, rapid diagnostic test for detection of patients with active TB. A new,
      rapid diagnostic method, (Cepheid) Xpert MTB/RIF Assay, is an automated sample
      preparation and real-time PCR instrument, which was shown to have good potential
      as an alternative to current reference standard sputum microscopy and culture.
      METHODS: We performed a clinical validation study on diagnostic accuracy of the
      Xpert MTB/RIF Assay in a TB and HIV endemic setting. Sputum samples from 292
      consecutively enrolled adults from Mbeya, Tanzania, with suspected TB were
      subject to analysis by the Xpert MTB/RIF Assay. The diagnostic performance of
      Xpert MTB/RIF Assay was compared to standard sputum smear microscopy and culture.
      Confirmed Mycobacterium tuberculosis in a positive culture was used as a
      reference standard for TB diagnosis. RESULTS: Xpert MTB/RIF Assay achieved 88.4%
      (95%CI = 78.4% to 94.9%) sensitivity among patients with a positive culture and
      99% (95%CI = 94.7% to 100.0%) specificity in patients who had no TB. HIV status
      did not affect test performance in 172 HIV-infected patients (58.9% of all
      participants). Seven additional cases (9.1% of 77) were detected by Xpert MTB/RIF
      Assay among the group of patients with clinical TB who were culture negative.
      Within 45 sputum samples which grew non-tuberculous mycobacteria the assay's
      specificity was 97.8% (95%CI = 88.2% to 99.9%). CONCLUSIONS: The Xpert MTB/RIF
      Assay is a highly sensitive, specific and rapid method for diagnosing TB which
      has potential to complement the current reference standard of TB diagnostics and
      increase its overall sensitivity. Its usefulness in detecting sputum smear and
      culture negative patients needs further study. Further evaluation in high burden
      TB and HIV areas under programmatic health care settings to ascertain
      applicability, cost-effectiveness, robustness and local acceptance are required.

PMID- 21738576
TI  - Linking neuronal ensembles by associative synaptic plasticity.
AB  - Synchronized activity in ensembles of neurons recruited by excitatory afferents
      is thought to contribute to the coding information in the brain. However, the
      mechanisms by which neuronal ensembles are generated and modified are not known.
      Here we show that in rat hippocampal slices associative synaptic plasticity
      enables ensembles of neurons to change by incorporating neurons belonging to
      different ensembles. Associative synaptic plasticity redistributes the
      composition of different ensembles recruited by distinct inputs such as to
      specifically increase the similarity between the ensembles. These results show
      that in the hippocampus, the ensemble of neurons recruited by a given afferent
      projection is fluid and can be rapidly and persistently modified to specifically
      include neurons from different ensembles. This linking of ensembles may
      contribute to the formation of associative memories.

PMID- 21738577
TI  - Parental height differences predict the need for an emergency caesarean section.
AB  - More than 30% of all pregnancies in the UK require some form of assistance at
      delivery, with one of the more severe forms of assistance being an emergency
      Caesarean section (ECS). Previously it has been shown that the likelihood of a
      delivery via ECS is positively associated with the birth weight and size of the
      newborn and negatively with maternal height. Paternal height affects skeletal
      growth and mass of the fetus, and thus might also affect pregnancy outcomes. We
      hypothesized that the effect of newborn birth weight on the risk of ECS would
      decrease with increasing maternal height. Similarly, we predicted that there
      would be an increase in ECS risk as a function of paternal height, but that this
      effect would be relative to maternal height (i.e., parental height differences).
      We used data from the Millennium Cohort Study: a large-scale survey (N = 18,819
      births) with data on babies born and their parents from the United Kingdom
      surveyed 9 to 12-months after birth. We found that in primiparous women, both
      maternal height and parental height differences interacted with birth weight and
      predicted the likelihood of an ECS. When carrying a heavy newborn, the risk of
      ECS was more than doubled for short women (46.3%) compared to tall women (21.7%),
      in agreement with earlier findings. For women of average height carrying a heavy
      newborn while having a relatively short compared to tall partner reduced the risk
      by 6.7%. In conclusion, the size of the baby, the height of the mother and
      parental height differences affect the likelihood of an ECS in primiparous women.

PMID- 21738578
TI  - Genomic organization of H2Av containing nucleosomes in Drosophila
      heterochromatin.
AB  - H2Av is a versatile histone variant that plays both positive and negative roles
      in transcription, DNA repair, and chromatin structure in Drosophila. H2Av, and
      its broader homolog H2A.Z, tend to be enriched toward 5' ends of genes, and exist
      in both euchromatin and heterochromatin. Its organization around euchromatin
      genes and other features have been described in many eukaryotic model organisms.
      However, less is known about H2Av nucleosome organization in heterochromatin.
      Here we report the properties and organization of individual H2Av nucleosomes
      around genes and transposable elements located in Drosophila heterochromatic
      regions. We compare the similarity and differences with that found in euchromatic
      regions. Our analyses suggest that nucleosomes are intrinsically positioned on
      inverted repeats of DNA transposable elements such as those related to the "1360"
      element, but are not intrinsically positioned on retrotransposon-related
      elements.

PMID- 21738579
TI  - H2S donor, S-propargyl-cysteine, increases CSE in SGC-7901 and cancer-induced
      mice: evidence for a novel anti-cancer effect of endogenous H2S?
AB  - BACKGROUND: S-propargyl-cysteine (SPRC), an H(2)S donor, is a structural analogue
      of S-allycysteine (SAC). It was investigated for its potential anti-cancer effect
      on SGC-7901 gastric cancer cells and the possible mechanisms that may be
      involved. METHODS AND FINDINGS: SPRC treatment significantly decreased cell
      viability, suppressed the proliferation and migration of SPRC-7901 gastric cancer
      cells, was pro-apoptotic as well as caused cell cycle arrest at the G(1)/S phase.
      In an in vivo study, intra-peritoneal injection of 50 mg/kg and 100 mg/kg of SPRC
      significantly reduced tumor weights and tumor volumes of gastric cancer implants
      in nude mice, with a tumor growth inhibition rate of 40-75%. SPRC also induced a
      pro-apoptotic effect in cancer tissues and elevated the expressions of p53 and
      Bax in tumors and cells. SPRC treatment also increased protein expression of
      cystathione-gamma-lyase (CSE) in cells and tumors, and elevated H(2)S levels in
      cell culture media, plasma and tumoral CSE activity of gastric cancer-induced
      nude mice by 2, 2.3 and 1.4 fold, respectively. Most of the anti-cancer functions
      of SPRC on cells and tumors were significantly suppressed by PAG, an inhibitor of
      CSE activity. CONCLUSIONS: Taken together, the results of our study provide
      insights into a novel anti-cancer effect of H(2)S as well as of SPRC on gastric
      cancer through inducing the activity of a new target, CSE.

PMID- 21738580
TI  - Role of the mitochondria in immune-mediated apoptotic death of the human
      pancreatic beta cell line betaLox5.
AB  - Mitochondria are indispensable in the life and death of many types of eukaryotic
      cells. In pancreatic beta cells, mitochondria play an essential role in the
      secretion of insulin, a hormone that regulates blood glucose levels. Unregulated
      blood glucose is a hallmark symptom of diabetes. The onset of Type 1 diabetes is
      preceded by autoimmune-mediated destruction of beta cells. However, the exact
      role of mitochondria has not been assessed in beta cell death. In this study, we
      examine the role of mitochondria in both Fas- and proinflammatory cytokine
      mediated destruction of the human beta cell line, betaLox5. IFNgamma primed
      betaLox5 cells for apoptosis by elevating cell surface Fas. Consequently,
      betaLox5 cells were killed by caspase-dependent apoptosis by agonistic activation
      of Fas, but only after priming with IFNgamma. This beta cell line undergoes both
      apoptotic and necrotic cell death after incubation with the combination of the
      proinflammatory cytokines IFNgamma and TNFalpha. Additionally, both caspase
      dependent and -independent mechanisms that require proper mitochondrial function
      are involved. Mitochondrial contributions to betaLox5 cell death were analyzed
      using mitochondrial DNA (mtDNA) depleted betaLox5 cells, or betaLox5 rho(0)
      cells. betaLox5 rho(0) cells are not sensitive to IFNgamma and TNFalpha killing,
      indicating a direct role for the mitochondria in cytokine-induced cell death of
      the parental cell line. However, betaLox5 rho(0) cells are susceptible to Fas
      killing, implicating caspase-dependent extrinsic apoptotic death is the mechanism
      by which these human beta cells die after Fas ligation. These data support the
      hypothesis that immune mediators kill betaLox5 cells by both mitochondrial
      dependent intrinsic and caspase-dependent extrinsic pathways.

PMID- 21738581
TI  - Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in
      patients with pancreatic cancer.
AB  - microRNAs (miRs) modulate the expression levels of mRNAs and proteins and can
      thus contribute to cancer initiation and progression. In addition to their
      intracelluar function, miRs are released from cells and shed into the
      circulation. We postulated that circulating miRs could provide insight into
      pathways altered during cancer progression and may indicate responses to
      treatment. Here we focus on pancreatic cancer malignant progression. We report
      that changes in miR expression patterns during progression of normal tissues to
      invasive pancreatic adenocarcinoma in the p48-Cre/LSL-Kras(G12D) mouse model
      mirrors the miR changes observed in human pancreatic cancer tissues. miR-148a/b
      and miR-375 expression were found decreased whereas miR-10, miR-21, miR-100 and
      miR-155 were increased when comparing normal tissues, premalignant lesions and
      invasive carcinoma in the mouse model. Predicted target mRNAs FGFR1 (miR-10) and
      MLH1 (miR-155) were found downregulated. Quantitation of nine microRNAs in plasma
      samples from patients distinguished pancreatic cancers from other cancers as well
      as non-cancerous pancreatic disease. Finally, gemcitabine treatment of control
      animals and p48-Cre/LSL-Kras(G12D) animals with pancreatic cancer caused distinct
      and up to 60-fold changes in circulating miRs that indicate differential drug
      effects on normal and cancer tissues. These findings support the significance of
      detecting miRs in the circulation and suggests that circulating miRs could serve
      as indicators of drug response.

PMID- 21738582
TI  - N-terminal Gly(224)-Gly(411) domain in Listeria adhesion protein interacts with
      host receptor Hsp60.
AB  - BACKGROUND: Listeria adhesion protein (LAP) is a housekeeping bifunctional enzyme
      consisting of N-terminal acetaldehyde dehydrogenase (ALDH) and C-terminal alcohol
      dehydrogenase (ADH). It aids Listeria monocytogenes in crossing the epithelial
      barrier through a paracellular route by interacting with its host receptor, heat
      shock protein 60 (Hsp60). To gain insight into the binding interaction between
      LAP and Hsp60, LAP subdomain(s) participating in the Hsp60 interaction were
      investigated. METHODS: Using a ModBase structural model, LAP was divided into 4
      putative subdomains: the ALDH region contains N1 (Met(1)-Pro(223)) and N2
      (Gly(224)-Gly(411)), and the ADH region contains C1 (Gly(412)-Val(648)) and C2
      (Pro(649)-Val(866)). Each subdomain was cloned and overexpressed in Escherichia
      coli and purified. Purified subdomains were used in ligand overlay,
      immunofluorescence, and bead-based epithelial cell adhesion assays to analyze
      each domain's affinity toward Hsp60 protein or human ileocecal epithelial HCT-8
      cells. RESULTS: The N2 subdomain exhibited the greatest affinity for Hsp60 with a
      K(D) of 9.50+/-2.6 nM. The K(D) of full-length LAP (7.2+/-0.5 nM) to Hsp60 was
      comparable to the N2 value. Microspheres (1 um diameter) coated with N2 subdomain
      showed significantly (P<0.05) higher binding to HCT-8 cells than beads coated
      with other subdomains and this binding was inhibited when HCT-8 cells were
      pretreated with anti-Hsp60 antibody to specifically block epithelial Hsp60.
      Furthermore, HCT-8 cells pretreated with purified N2 subdomain also reduced L.
      monocytogenes adhesion by about 4 log confirming its involvement in interaction
      with epithelial cells. CONCLUSION: These data indicate that the N2 subdomain in
      the LAP ALDH domain is critical in initiating interaction with mammalian cell
      receptor Hsp60 providing insight into the molecular mechanism of pathogenesis for
      the development of potential anti-listerial control strategies.

PMID- 21738583
TI  - Regulation of retinoschisin secretion in Weri-Rb1 cells by the F-actin and
      microtubule cytoskeleton.
AB  - Retinoschisin is encoded by the gene responsible for X-linked retinoschisis
      (XLRS), an early onset macular degeneration that results in a splitting of the
      inner layers of the retina and severe loss in vision. Retinoschisin is
      predominantly expressed and secreted from photoreceptor cells as a homo-oligomer
      protein; it then associates with the surface of retinal cells and maintains the
      retina cellular architecture. Many missense mutations in the XLRS1 gene are known
      to cause intracellular retention of retinoschisin, indicating that the secretion
      process of the protein is a critical step for its normal function in the retina.
      However, the molecular mechanisms underlying retinoschisin's secretion remain to
      be fully elucidated. In this study, we investigated the role of the F-actin
      cytoskeleton in the secretion of retinoschisin by treating Weri-Rb1 cells, which
      are known to secrete retinoschisin, with cytochalasin D, jasplakinolide, Y-27632,
      and dibutyryl cGMP. Our results show that cytochalasin D and jasplakinolide
      inhibit retinoschisin secretion, whereas Y-27632 and dibutyryl cGMP enhance
      secretion causing F-actin alterations. We also demonstrate that high
      concentrations of taxol, which hyperpolymerizes microtubules, inhibit
      retinoschisin secretion. Our data suggest that retinoschisin secretion is
      regulated by the F-actin cytoskeleton, that cGMP or inhibition of ROCK alters F
      actin structure enhancing the secretion, and that the microtubule cytoskeleton is
      also involved in this process.

PMID- 21738584
TI  - Sequence- and interactome-based prediction of viral protein hotspots targeting
      host proteins: a case study for HIV Nef.
AB  - Virus proteins alter protein pathways of the host toward the synthesis of viral
      particles by breaking and making edges via binding to host proteins. In this
      study, we developed a computational approach to predict viral sequence hotspots
      for binding to host proteins based on sequences of viral and host proteins and
      literature-curated virus-host protein interactome data. We use a motif discovery
      algorithm repeatedly on collections of sequences of viral proteins and immediate
      binding partners of their host targets and choose only those motifs that are
      conserved on viral sequences and highly statistically enriched among binding
      partners of virus protein targeted host proteins. Our results match experimental
      data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA
      A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor
      predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted
      hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in
      modulating virus-host interactions. Host proteins potentially targeted or
      outcompeted by Nef appear crowding the T cell receptor, natural killer cell
      mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef
      motifs on multiple alignments of hepatitis C protein NS5A produces results
      consistent with literature, indicating the potential value of the hotspot
      discovery in advancing our understanding of virus-host crosstalk.

PMID- 21738585
TI  - Assessing tuberculosis case fatality ratio: a meta-analysis.
AB  - BACKGROUND: Recently, the tuberculosis (TB) Task Force Impact Measurement
      acknowledged the need to review the assumptions underlying the TB mortality
      estimates published annually by the World Health Organization (WHO). TB mortality
      is indirectly measured by multiplying estimated TB incidence with estimated case
      fatality ratio (CFR). We conducted a meta-analysis to estimate the TB case
      fatality ratio in TB patients having initiated TB treatment. METHODS: We searched
      for eligible studies in the PubMed and Embase databases through March 4(th) 2011
      and by reference listing of relevant review articles. Main analyses included the
      estimation of the pooled percentages of: a) TB patients dying due to TB after
      having initiated TB treatment and b) TB patients dying during TB treatment.
      Pooled percentages were estimated using random effects regression models on the
      combined patient population from all studies. MAIN RESULTS: We identified 69
      relevant studies of which 22 provided data on mortality due to TB and 59 provided
      data on mortality during TB treatment. Among HIV infected persons the pooled
      percentage of TB patients dying due to TB was 9.2% (95% Confidence Interval (CI):
      3.7%-14.7%) and among HIV uninfected persons 3.0% (95% CI: -1.2%-7.4%) based on
      the results of eight and three studies respectively providing data for this
      analyses. The pooled percentage of TB patients dying during TB treatment was
      18.8% (95% CI: 14.8%-22.8%) among HIV infected patients and 3.5% (95% CI: 2.0%
      4.92%) among HIV uninfected patients based on the results of 27 and 19 studies
      respectively. CONCLUSION: The results of the literature review are useful in
      generating prior distributions of CFR in countries with vital registration
      systems and have contributed towards revised estimates of TB mortality This
      literature review did not provide us with all data needed for a valid estimation
      of TB CFR in TB patients initiating TB treatment.

PMID- 21738586
TI  - Beyond R0: demographic models for variability of lifetime reproductive output.
AB  - The net reproductive rate R0 measures the expected lifetime reproductive output
      of an individual, and plays an important role in demography, ecology, evolution,
      and epidemiology. Well-established methods exist to calculate it from age- or
      stage-classified demographic data. As an expectation, R0 provides no information
      on variability; empirical measurements of lifetime reproduction universally show
      high levels of variability, and often positive skewness among individuals. This
      is often interpreted as evidence of heterogeneity, and thus of an opportunity for
      natural selection. However, variability provides evidence of heterogeneity only
      if it exceeds the level of variability to be expected in a cohort of identical
      individuals all experiencing the same vital rates. Such comparisons require a way
      to calculate the statistics of lifetime reproduction from demographic data. Here,
      a new approach is presented, using the theory of Markov chains with rewards,
      obtaining all the moments of the distribution of lifetime reproduction. The
      approach applies to age- or stage-classified models, to constant, periodic, or
      stochastic environments, and to any kind of reproductive schedule. As examples, I
      analyze data from six empirical studies, of a variety of animal and plant taxa
      (nematodes, polychaetes, humans, and several species of perennial plants).

PMID- 21738587
TI  - Interleukin 7 from maternal milk crosses the intestinal barrier and modulates T
      cell development in offspring.
AB  - BACKGROUND: Breastfeeding protects against illnesses and death in hazardous
      environments, an effect partly mediated by improved immune function. One
      hypothesis suggests that factors within milk supplement the inadequate immune
      response of the offspring, but this has not been able to account for a series of
      observations showing that factors within maternally derived milk may supplement
      the development of the immune system through a direct effect on the primary
      lymphoid organs. In a previous human study we reported evidence suggesting a link
      between IL-7 in breast milk and the thymic output of infants. Here we report
      evidence in mice of direct action of maternally-derived IL-7 on T cell
      development in the offspring. METHODS AND FINDINGS: We have used recombinant IL-7
      labelled with a fluorescent dye to trace the movement in live mice of IL-7 from
      the stomach across the gut and into the lymphoid tissues. To validate the
      functional ability of maternally derived IL-7 we cross fostered IL-7 knock-out
      mice onto normal wild type mothers. Subsets of thymocytes and populations of
      peripheral T cells were significantly higher than those found in knock-out mice
      receiving milk from IL-7 knock-out mothers. CONCLUSIONS/SIGNIFICANCE: Our study
      provides direct evidence that interleukin 7, a factor which is critical in the
      development of T lymphocytes, when maternally derived can transfer across the
      intestine of the offspring, increase T cell production in the thymus and support
      the survival of T cells in the peripheral secondary lymphoid tissue.

PMID- 21738588
TI  - Increased genetic variance of BMI with a higher prevalence of obesity.
AB  - BACKGROUND AND OBJECTIVES: There is no doubt that the dramatic worldwide increase
      in obesity prevalence is due to changes in environmental factors. However, twin
      studies suggest that genetic differences are responsible for the major part of
      the variation in body mass index (BMI) and other measures of body fatness within
      populations. Several recent studies suggest that the genetic effects on adiposity
      may be stronger when combined with presumed risk factors for obesity. We tested
      the hypothesis that a higher prevalence of obesity and overweight and a higher
      BMI mean is associated with a larger genetic variation in BMI. METHODS: The data
      consisted of self-reported height and weight from two Danish twin surveys in 1994
      and 2002. A total of 15,017 monozygotic and dizygotic twin pairs were divided
      into subgroups by year of birth (from 1931 through 1982) and sex. The genetic and
      environmental variance components of BMI were calculated for each subgroup using
      the classical twin design. Likewise, the prevalence of obesity, prevalence of
      overweight and the mean of the BMI distribution was calculated for each subgroup
      and tested as explanatory variables in a random effects meta-regression model
      with the square root of the additive genetic variance (equal to the standard
      deviation) as the dependent variable. RESULTS: The size of additive genetic
      variation was positively and significantly associated with obesity prevalence (p
      = 0.001) and the mean of the BMI distribution (p = 0.015). The association with
      prevalence of overweight was positive but not statistically significant (p =
      0.177). CONCLUSION: The results suggest that the genetic variation in BMI
      increases as the prevalence of obesity, prevalence of overweight and the BMI mean
      increases. The findings suggest that the genes related to body fatness are
      expressed more aggressively under the influence of an obesity-promoting
      environment.

PMID- 21738589
TI  - Social and demographic effects of anthropogenic mortality: a test of the
      compensatory mortality hypothesis in the red wolf.
AB  - Whether anthropogenic mortality is additive or compensatory to natural mortality
      in animal populations has long been a question of theoretical and practical
      importance. Theoretically, under density-dependent conditions populations
      compensate for anthropogenic mortality through decreases in natural mortality
      and/or increases in productivity, but recent studies of large carnivores suggest
      that anthropogenic mortality can be fully additive to natural mortality and
      thereby constrain annual survival and population growth rate. Nevertheless,
      mechanisms underlying either compensatory or additive effects continue to be
      poorly understood. Using long-term data on a reintroduced population of the red
      wolf, we tested for evidence of additive vs. compensatory effects of
      anthropogenic mortality on annual survival and population growth rates, and the
      preservation and reproductive success of breeding pairs. We found that
      anthropogenic mortality had a strong additive effect on annual survival and
      population growth rate at low population density, though there was evidence for
      compensation in population growth at high density. When involving the death of a
      breeder, anthropogenic mortality was also additive to natural rates of breeding
      pair dissolution, resulting in a net decrease in the annual preservation of
      existing breeding pairs. However, though the disbanding of a pack following death
      of a breeder resulted in fewer recruits per litter relative to stable packs,
      there was no relationship between natural rates of pair dissolution and
      population growth rate at either high or low density. Thus we propose that short
      term additive effects of anthropogenic mortality on population growth in the red
      wolf population at low density were primarily a result of direct mortality of
      adults rather than indirect socially-mediated effects resulting in reduced
      recruitment. Finally, we also demonstrate that per capita recruitment and the
      proportion of adults that became reproductive declined steeply with increasing
      population density, suggesting that there is potential for density-dependent
      compensation of anthropogenically-mediated population regulation.

PMID- 21738590
TI  - Rapid changes in phospho-MAP/tau epitopes during neuronal stress: cofilin-actin
      rods primarily recruit microtubule binding domain epitopes.
AB  - Abnormal mitochondrial function is a widely reported contributor to
      neurodegenerative disease including Alzheimer's disease (AD), however, a
      mechanistic link between mitochondrial dysfunction and the initiation of
      neuropathology remains elusive. In AD, one of the earliest hallmark pathologies
      is neuropil threads comprising accumulated hyperphosphorylated microtubule
      associated protein (MAP) tau in neurites. Rod-like aggregates of actin and its
      associated protein cofilin (AC rods) also occur in AD. Using a series of
      antibodies--AT270, AT8, AT100, S214, AT180, 12E8, S396, S404 and S422--raised
      against different phosphoepitopes on tau, we characterize the pattern of
      expression and re-distribution in neurites of these phosphoepitope labels during
      mitochondrial inhibition. Employing chick primary neuron cultures, we demonstrate
      that epitopes recognized by the monoclonal antibody 12E8, are the only species
      rapidly recruited into AC rods. These results were recapitulated with the actin
      depolymerizing drug Latrunculin B, which induces AC rods and a concomitant
      increase in the 12E8 signal measured on Western blot. This suggests that AC rods
      may be one way in which MAP redistribution and phosphorylation is influenced in
      neurons during mitochondrial stress and potentially in the early pathogenesis of
      AD.

PMID- 21738591
TI  - Variation in seed dormancy quantitative trait loci in Arabidopsis thaliana
      originating from one site.
AB  - A Quantitative Trait Locus (QTL) analysis was performed using two novel
      Recombinant Inbred Line (RIL) populations, derived from the progeny between two
      Arabidopsis thaliana genotypes collected at the same site in Kyoto (Japan)
      crossed with the reference laboratory strain Landsberg erecta (Ler). We used
      these two RIL populations to determine the genetic basis of seed dormancy and
      flowering time, which are assumed to be the main traits controlling life history
      variation in Arabidopsis. The analysis revealed quantitative variation for seed
      dormancy that is associated with allelic variation at the seed dormancy QTL DOG1
      (for Delay Of Germination 1) in one population and at DOG6 in both. These DOG QTL
      have been previously identified using mapping populations derived from accessions
      collected at different sites around the world. Genetic variation within a
      population may enhance its ability to respond accurately to variation within and
      between seasons. In contrast, variation for flowering time, which also segregated
      within each mapping population, is mainly governed by the same QTL.

PMID- 21738592
TI  - The significance of the ProtDeform score for structure prediction and alignment.
AB  - BACKGROUND: When a researcher uses a program to align two proteins and gets a
      score, one of her main concerns is how often the program gives a similar score to
      pairs that are or are not in the same fold. This issue was analysed in detail
      recently for the program TM-align with its associated TM-score. It was shown that
      because the TM-score is length independent, it allows a P-value and a hit
      probability to be defined depending only on the score. Also, it was found that
      the TM-scores of gapless alignments closely follow an Extreme Value Distribution
      (EVD). The program ProtDeform for structural protein alignment was developed
      recently and is characterised by the ability to propose different transformations
      of different protein regions. Our goal is to analyse its associated score to
      allow a researcher to have objective reasons to prefer one aligner over another,
      and carry out a better interpretation of the output. RESULTS: The study on the
      ProtDeform score reveals that it is length independent in a wider score range
      than TM-scores and that PD-scores of gapless (random) alignments also
      approximately follow an EVD. On the CASP8 predictions, PD-scores and TM-scores,
      with respect to native structures, are highly correlated (0.95), and show that
      around a fifth of the predictions have a quality as low as 99.5% of the random
      scores. Using the Gold Standard benchmark, ProtDeform has lower probabilities of
      error than TM-align both at a similar speed. The analysis is extended to homology
      discrimination showing that, again, ProtDeform offers higher hit probabilities
      than TM-align. Finally, we suggest using three different P-values according to
      the three different contexts: Gapless alignments, optimised alignments for fold
      discrimination and that for superfamily discrimination. In conclusion, PD-scores
      are at the very least as valuable for prediction scoring as TM-scores, and on the
      protein classification problem, even more reliable.

PMID- 21738593
TI  - Regulation of Alr1 Mg transporter activity by intracellular magnesium.
AB  - Mg homeostasis is critical to eukaryotic cells, but the contribution of Mg
      transporter activity to homeostasis is not fully understood. In yeast, Mg uptake
      is primarily mediated by the Alr1 transporter, which also allows low affinity
      uptake of other divalent cations such as Ni(2+), Mn(2+), Zn(2+) and Co(2+). Using
      Ni(2+) uptake to assay Alr1 activity, we observed approximately nine-fold more
      activity under Mg-deficient conditions. The mnr2 mutation, which is thought to
      block release of vacuolar Mg stores, was associated with increased Alr1 activity,
      suggesting Alr1 was regulated by intracellular Mg supply. Consistent with a
      previous report of the regulation of Alr1 expression by Mg supply, Mg deficiency
      and the mnr2 mutation both increased the accumulation of a carboxy-terminal
      epitope-tagged version of the Alr1 protein (Alr1-HA). However, Mg supply had
      little effect on ALR1 promoter activity or mRNA levels. In addition, while Mg
      deficiency caused a seven-fold increase in Alr1-HA accumulation, the N-terminally
      tagged and untagged Alr1 proteins increased less than two-fold. These
      observations argue that the Mg-dependent accumulation of the C-terminal epitope
      tagged protein was primarily an artifact of its modification. Plasma membrane
      localization of YFP-tagged Alr1 was also unaffected by Mg supply, indicating that
      a change in Alr1 location did not explain the increased activity we observed. We
      conclude that variation in Alr1 protein accumulation or location does not make a
      substantial contribution to its regulation by Mg supply, suggesting Alr1 activity
      is directly regulated via as yet unknown mechanisms.

PMID- 21738594
TI  - A directed molecular evolution approach to improved immunogenicity of the HIV-1
      envelope glycoprotein.
AB  - A prophylactic vaccine is needed to slow the spread of HIV-1 infection.
      Optimization of the wild-type envelope glycoproteins to create immunogens that
      can elicit effective neutralizing antibodies is a high priority. Starting with
      ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in
      vitro homologous DNA recombination, we created chimeric gp120 variants that were
      screened for their ability to bind neutralizing monoclonal antibodies. Hundreds
      of variants were identified with novel antigenic phenotypes that exhibit
      considerable sequence diversity. Immunization of rabbits with these gp120
      variants demonstrated that the majority can induce neutralizing antibodies to HIV
      1. One novel variant, called ST-008, induced significantly improved neutralizing
      antibody responses when assayed against a large panel of primary HIV-1 isolates.
      Further study of various deletion constructs of ST-008 showed that the enhanced
      immunogenicity results from a combination of effective DNA priming, an enhanced
      V3-based response, and an improved response to the constant backbone sequences.

PMID- 21738595
TI  - Functional analysis of the two Brassica AP3 genes involved in apetalous and
      stamen carpelloid phenotypes.
AB  - The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes
      which encode MADS-box transcription factors and specify petal and stamen
      identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and
      AMS, of B. rapa and B. napus were investigated and two types of AP3 genes,
      B.AP3.a and B.AP3.b, were functional characterized. B.AP3.a and B.AP3.b share
      high similarity in amino acid sequences except for 8 residues difference located
      at the C-terminus. Loss of this 8 residues in B.AP3.b led to the change of PI
      derived motifs. Meanwhile, B.AP3.a specified petal and stamen development,
      whereas B.AP3.b only specified stamen development. In B. rapa, the mutations of
      both genes generated the SC mutant HGMS. In B. napus that contained two B.AP3.a
      and two B.AP3.b, loss of the two B.AP3.a functions was the key reason for the
      apetalous mutation, however, the loss-of-function in all four AP3 was related to
      the SC mutant AMS. We inferred that the 8 residues or the PI-derived motif in AP3
      gene probably relates to petal formation.

PMID- 21738596
TI  - Target region selection is a critical determinant of community fingerprints
      generated by 16S pyrosequencing.
AB  - Pyrosequencing of 16S rRNA genes allows for in-depth characterization of complex
      microbial communities. Although it is known that primer selection can influence
      the profile of a community generated by sequencing, the extent and severity of
      this bias on deep-sequencing methodologies is not well elucidated. We tested the
      hypothesis that the hypervariable region targeted for sequencing and primer
      degeneracy play important roles in influencing the composition of 16S pyrotag
      communities. Subgingival plaque from deep sites of current smokers with chronic
      periodontitis was analyzed using Sanger sequencing and pyrosequencing using 4
      primer pairs. Greater numbers of species were detected by pyrosequencing than by
      Sanger sequencing. Rare taxa constituted nearly 6% of each pyrotag community and
      less than 1% of the Sanger sequencing community. However, the different target
      regions selected for pyrosequencing did not demonstrate a significant difference
      in the number of rare and abundant taxa detected. The genera Prevotella,
      Fusobacterium, Streptococcus, Granulicatella, Bacteroides, Porphyromonas and
      Treponema were abundant when the V1-V3 region was targeted, while Streptococcus,
      Treponema, Prevotella, Eubacterium, Porphyromonas, Campylobacter and Enterococcus
      predominated in the community generated by V4-V6 primers, and the most numerous
      genera in the V7-V9 community were Veillonella, Streptococcus, Eubacterium,
      Enterococcus, Treponema, Catonella and Selenomonas. Targeting the V4-V6 region
      failed to detect the genus Fusobacterium, while the taxa Selenomonas, TM7 and
      Mycoplasma were not detected by the V7-V9 primer pairs. The communities generated
      by degenerate and non-degenerate primers did not demonstrate significant
      differences. Averaging the community fingerprints generated by V1-V3 and V7-V9
      primers provided results similar to Sanger sequencing, while allowing a
      significantly greater depth of coverage than is possible with Sanger sequencing.
      It is therefore important to use primers targeted to these two regions of the 16S
      rRNA gene in all deep-sequencing efforts to obtain representational
      characterization of complex microbial communities.

PMID- 21738597
TI  - Improved survival of HIV-1-infected patients with progressive multifocal
      leukoencephalopathy receiving early 5-drug combination antiretroviral therapy.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML), a rare devastating
      demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely
      immunocompromised patients, most of whom have advanced-stage HIV infection.
      Despite combination antiretroviral therapy (cART), 50% of patients die within 6
      months of PML onset. We conducted a multicenter, open-label pilot trial
      evaluating the survival benefit of a five-drug cART designed to accelerate HIV
      replication decay and JCV-specific immune recovery. METHODS AND FINDINGS: All the
      patients received an optimized cART with three or more drugs for 12 months, plus
      the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was
      the one-year survival rate. A total of 28 patients were enrolled. At entry,
      median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable
      plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4.
      The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93).
      At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12,
      81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell
      increment was 105 per microliter. In univariate analysis, higher total and naive
      CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with
      better survival. JCV-specific functional memory CD4+ T-cell responses, based on a
      proliferation assay, were detected in 4% of patients at baseline and 43% at M12
      (P = 0.008). CONCLUSIONS: The early use of five-drug cART after PML diagnosis
      appears to improve survival. This is associated with recovery of anti-JCV T-cell
      responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive
      subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors
      for death. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120367.

PMID- 21738598
TI  - Molecular modelling of the emergence of azole resistance in Mycosphaerella
      graminicola.
AB  - A structural rationale for recent emergence of azole (imidazole and triazole)
      resistance associated with CYP51 mutations in the wheat pathogen Mycosphaerella
      graminicola is presented, attained by homology modelling of the wild type protein
      and 13 variant proteins. The novel molecular models of M. graminicola CYP51 are
      based on multiple homologues, individually identified for each variant, rather
      than using a single structural scaffold, providing a robust structure-function
      rationale for the binding of azoles, including important fungal specific regions
      for which no structural information is available. The wild type binding pocket
      reveals specific residues in close proximity to the bound azole molecules that
      are subject to alteration in the variants. This implicates azole ligands as
      important agents exerting selection on specific regions bordering the pocket,
      that become the focus of genetic mutation events, leading to reduced sensitivity
      to that group of related compounds. Collectively, the models account for several
      observed functional effects of specific alterations, including loss of
      triadimenol sensitivity in the Y137F variant, lower sensitivity to tebuconazole
      of I381V variants and increased resistance to prochloraz of V136A variants.
      Deletion of Y459 and G460, which brings about removal of that entire section of
      beta turn from the vicinity of the binding pocket, confers resistance to
      tebuconazole and epoxiconazole, but sensitivity to prochloraz in variants
      carrying a combination of A379G I381V DeltaY459/G460. Measurements of binding
      pocket volume proved useful in assessment of scope for general resistance to
      azoles by virtue of their accommodation without bonding interaction, particularly
      when combined with analysis of change in positions of key amino acids. It is
      possible to predict the likely binding orientation of an azole molecule in any of
      the variant CYPs, providing potential for an in silico screening system and
      reliable predictive approach to assess the probability of particular variants
      exhibiting resistance to particular azole fungicides.

PMID- 21738599
TI  - Global microRNA expression profiling identifies MiR-210 associated with tumor
      proliferation, invasion and poor clinical outcome in breast cancer.
AB  - PURPOSE: Aberrant microRNA (miRNA) expression is associated with cancer and has
      potential diagnostic and prognostic value in various malignancies. In this study,
      we investigated miRNA profiling as a complementary tool to improve our
      understanding of breast cancer (BC) biology and to assess whether miRNA
      expression could predict clinical outcome of BC patients. EXPERIMENTAL DESIGN:
      Global miRNA expression profiling using microarray technology was conducted in 56
      systemically untreated BC patients who had corresponding mRNA expression profiles
      available. Results were further confirmed using qRT-PCR in an independent dataset
      of 89 ER-positive BC patients homogeneously treated with tamoxifen only. MiR-210
      functional analyses were performed in MCF7 and MDA-MB-231 BC cell lines using
      lentiviral transduction. RESULTS: Estrogen receptor (ER) status, tumor grade and
      our previously developed gene expression grade index (GGI) were associated with
      distinct miRNA profiles. Several miRNAs were found to be clinically relevant,
      including miR-210, its expression being associated with tumor proliferation and
      differentiation. Furthermore, miR-210 was associated with poor clinical outcome
      in ER-positive, tamoxifen-treated BC patients. Interestingly, the prognostic
      performance of miR-210 was similar to several reported multi-gene signatures,
      highlighting its important role in BC differentiation and tumor progression.
      Functional analyses in BC cell lines revealed that miR-210 is involved in cell
      proliferation, migration and invasion. CONCLUSIONS: This integrated analysis
      combining miRNA and mRNA expression demonstrates that miRNA expression provides
      additional biological information beyond mRNA expression. Expression of miR-210
      is linked to tumor proliferation and appears to be a strong potential biomarker
      of clinical outcome in BC.

PMID- 21738600
TI  - On identifying the optimal number of population clusters via the deviance
      information criterion.
AB  - Inferring population structure using bayesian clustering programs often requires
      a priori specification of the number of subpopulations, K, from which the sample
      has been drawn. Here, we explore the utility of a common bayesian model selection
      criterion, the Deviance Information Criterion (DIC), for estimating K. We
      evaluate the accuracy of DIC, as well as other popular approaches, on datasets
      generated by coalescent simulations under various demographic scenarios. We find
      that DIC outperforms competing methods in many genetic contexts, validating its
      application in assessing population structure.

PMID- 21738601
TI  - A ribosomal misincorporation of Lys for Arg in human triosephosphate isomerase
      expressed in Escherichia coli gives rise to two protein populations.
AB  - We previously observed that human homodimeric triosephosphate isomerase (HsTIM)
      expressed in Escherichia coli and purified to apparent homogeneity exhibits two
      significantly different thermal transitions. A detailed exploration of the
      phenomenon showed that the preparations contain two proteins; one has the
      expected theoretical mass, while the mass of the other is 28 Da lower. The two
      proteins were separated by size exclusion chromatography in 3 M urea. Both
      proteins correspond to HsTIM as shown by Tandem Mass Spectrometry (LC/ESI-MS/MS).
      The two proteins were present in nearly equimolar amounts under certain growth
      conditions. They were catalytically active, but differed in molecular mass,
      thermostability, susceptibility to urea and proteinase K. An analysis of the
      nucleotides in the human TIM gene revealed the presence of six codons that are
      not commonly used in E. coli. We examined if they were related to the formation
      of the two proteins. We found that expression of the enzyme in a strain that
      contains extra copies of genes that encode for tRNAs that frequently limit
      translation of heterologous proteins (Arg, Ile, Leu), as well as silent mutations
      of two consecutive rare Arg codons (positions 98 and 99), led to the exclusive
      production of the more stable protein. Further analysis by LC/ESI-MS/MS showed
      that the 28 Da mass difference is due to the substitution of a Lys for an Arg
      residue at position 99. Overall, our work shows that two proteins with different
      biochemical and biophysical properties that coexist in the same cell environment
      are translated from the same nucleotide sequence frame.

PMID- 21738602
TI  - Particle swarm optimization with reinforcement learning for the prediction of CpG
      islands in the human genome.
AB  - BACKGROUND: Regions with abundant GC nucleotides, a high CpG number, and a length
      greater than 200 bp in a genome are often referred to as CpG islands. These
      islands are usually located in the 5' end of genes. Recently, several algorithms
      for the prediction of CpG islands have been proposed. METHODOLOGY/PRINCIPAL
      FINDINGS: We propose here a new method called CPSORL to predict CpG islands,
      which consists of a complement particle swarm optimization algorithm combined
      with reinforcement learning to predict CpG islands more reliably. Several CpG
      island prediction tools equipped with the sliding window technique have been
      developed previously. However, the quality of the results seems to rely too much
      on the choices that are made for the window sizes, and thus these methods leave
      room for improvement. CONCLUSIONS/SIGNIFICANCE: Experimental results indicate
      that CPSORL provides results of a higher sensitivity and a higher correlation
      coefficient in all selected experimental contigs than the other methods it was
      compared to (CpGIS, CpGcluster, CpGProd and CpGPlot). A higher number of CpG
      islands were identified in chromosomes 21 and 22 of the human genome than with
      the other methods from the literature. CPSORL also achieved the highest coverage
      rate (3.4%). CPSORL is an application for identifying promoter and TSS regions
      associated with CpG islands in entire human genomic. When compared to CpGcluster,
      the islands predicted by CPSORL covered a larger region in the TSS (12.2%) and
      promoter (26.1%) region. If Alu sequences are considered, the islands predicted
      by CPSORL (Alu) covered a larger TSS (40.5%) and promoter (67.8%) region than
      CpGIS. Furthermore, CPSORL was used to verify that the average methylation
      density was 5.33% for CpG islands in the entire human genome.

PMID- 21738603
TI  - Characterization of protein-protein interaction interfaces from a single species.
AB  - Most proteins attain their biological functions through specific interactions
      with other proteins. Thus, the study of protein-protein interactions and the
      interfaces that mediate these interactions is of prime importance for the
      understanding of biological function. In particular the precise determinants of
      binding specificity and their contributions to binding energy within protein
      interfaces are not well understood. In order to better understand these
      determinants an appropriate description of the interaction surface is needed.
      Available data from the yeast Saccharomyces cerevisiae allow us to focus on a
      single species and to use all the available structures, correcting for
      redundancy, instead of using structural representatives. This allows us to
      control for potentially confounding factors that may affect sequence
      propensities. We find a significant contribution of main-chain atoms to protein
      protein interactions. These include interactions both with other main-chain and
      side-chain atoms on the interacting chain. We find that the type of interaction
      depends on both amino acid and secondary structure type involved in the contact.
      For example, residues in alpha-helices and large amino acids are the most likely
      to be involved in interactions through their side-chain atoms. We find an
      intriguing homogeneity when calculating the average solvation energy of different
      areas of the protein surface. Unexpectedly, homo- and hetero-complexes have quite
      similar results for all analyses. Our findings demonstrate that the manner in
      which protein-protein interactions are formed is determined by the residue type
      and the secondary structure found in the interface. However the homogeneity of
      the desolvation energy despite heterogeneity of interface properties suggests a
      complex relationship between interface composition and binding energy.

PMID- 21738604
TI  - Large-scale assessment of the zebrafish embryo as a possible predictive model in
      toxicity testing.
AB  - BACKGROUND: In the drug discovery pipeline, safety pharmacology is a major issue.
      The zebrafish has been proposed as a model that can bridge the gap in this field
      between cell assays (which are cost-effective, but low in data content) and
      rodent assays (which are high in data content, but less cost-efficient). However,
      zebrafish assays are only likely to be useful if they can be shown to have high
      predictive power. We examined this issue by assaying 60 water-soluble compounds
      representing a range of chemical classes and toxicological mechanisms.
      METHODOLOGY/PRINCIPAL FINDINGS: Over 20,000 wild-type zebrafish embryos
      (including controls) were cultured individually in defined buffer in 96-well
      plates. Embryos were exposed for a 96 hour period starting at 24 hours post
      fertilization. A logarithmic concentration series was used for range-finding,
      followed by a narrower geometric series for LC(50) determination. Zebrafish
      embryo LC(50) (log mmol/L), and published data on rodent LD(50) (log mmol/kg),
      were found to be strongly correlated (using Kendall's rank correlation tau and
      Pearson's product-moment correlation). The slope of the regression line for the
      full set of compounds was 0.73403. However, we found that the slope was strongly
      influenced by compound class. Thus, while most compounds had a similar toxicity
      level in both species, some compounds were markedly more toxic in zebrafish than
      in rodents, or vice versa. CONCLUSIONS: For the substances examined here, in
      aggregate, the zebrafish embryo model has good predictivity for toxicity in
      rodents. However, the correlation between zebrafish and rodent toxicity varies
      considerably between individual compounds and compound class. We discuss the
      strengths and limitations of the zebrafish model in light of these findings.

PMID- 21738605
TI  - Oldest known Eucalyptus macrofossils are from South America.
AB  - The evolutionary history of Eucalyptus and the eucalypts, the larger clade of
      seven genera including Eucalyptus that today have a natural distribution almost
      exclusively in Australasia, is poorly documented from the fossil record. Little
      physical evidence exists bearing on the ancient geographical distributions or
      morphologies of plants within the clade. Herein, we introduce fossil material of
      Eucalyptus from the early Eocene (ca. 51.9 Ma) Laguna del Hunco paleoflora of
      Chubut Province, Argentina; specimens include multiple leaves, infructescences,
      and dispersed capsules, several flower buds, and a single flower. Morphological
      similarities that relate the fossils to extant eucalypts include leaf shape,
      venation, and epidermal oil glands; infructescence structure; valvate capsulate
      fruits; and operculate flower buds. The presence of a staminophore scar on the
      fruits links them to Eucalyptus, and the presence of a transverse scar on the
      flower buds indicates a relationship to Eucalyptus subgenus Symphyomyrtus.
      Phylogenetic analyses of morphological data alone and combined with aligned
      sequence data from a prior study including 16 extant eucalypts, one outgroup, and
      a terminal representing the fossils indicate that the fossils are nested within
      Eucalyptus. These are the only illustrated Eucalyptus fossils that are
      definitively Eocene in age, and the only conclusively identified extant or fossil
      eucalypts naturally occurring outside of Australasia and adjacent Mindanao. Thus,
      these fossils indicate that the evolution of the eucalypt group is not
      constrained to a single region. Moreover, they strengthen the taxonomic
      connections between the Laguna del Hunco paleoflora and extant subtropical and
      tropical Australasia, one of the three major ecologic-geographic elements of the
      Laguna del Hunco paleoflora. The age and affinities of the fossils also indicate
      that Eucalyptus subgenus Symphyomyrtus is older than previously supposed.
      Paleoecological data indicate that the Patagonian Eucalyptus dominated
      volcanically disturbed areas adjacent to standing rainforest surrounding an
      Eocene caldera lake.

PMID- 21738606
TI  - A flexible approach for highly multiplexed candidate gene targeted resequencing.
AB  - We have developed an integrated strategy for targeted resequencing and analysis
      of gene subsets from the human exome for variants. Our capture technology is
      geared towards resequencing gene subsets substantially larger than can be done
      efficiently with simplex or multiplex PCR but smaller in scale than exome
      sequencing. We describe all the steps from the initial capture assay to single
      nucleotide variant (SNV) discovery. The capture methodology uses in-solution 80
      mer oligonucleotides. To provide optimal flexibility in choosing human gene
      targets, we designed an in silico set of oligonucleotides, the Human OligoExome,
      that covers the gene exons annotated by the Consensus Coding Sequencing Project
      (CCDS). This resource is openly available as an Internet accessible database
      where one can download capture oligonucleotides sequences for any CCDS gene and
      design custom capture assays. Using this resource, we demonstrated the
      flexibility of this assay by custom designing capture assays ranging from 10 to
      over 100 gene targets with total capture sizes from over 100 Kilobases to nearly
      one Megabase. We established a method to reduce capture variability and
      incorporated indexing schemes to increase sample throughput. Our approach has
      multiple applications that include but are not limited to population targeted
      resequencing studies of specific gene subsets, validation of variants discovered
      in whole genome sequencing surveys and possible diagnostic analysis of disease
      gene subsets. We also present a cost analysis demonstrating its cost
      effectiveness for large population studies.

PMID- 21738607
TI  - A computational model of visual anisotropy.
AB  - Visual anisotropy has been demonstrated in multiple tasks where performance
      differs between vertical, horizontal, and oblique orientations of the stimuli. We
      explain some principles of visual anisotropy by anisotropic smoothing, which is
      based on a variation on Koenderink's approach in [1]. We tested the theory by
      presenting gaussian elongated luminance profiles and measuring the perceived
      orientations by means of an adjustment task. Our framework is based on the
      smoothing of the image with elliptical gaussian kernels and it correctly
      predicted an illusory orientation bias towards the vertical axis. We discuss the
      scope of the theory in the context of other anisotropies in perception.

PMID- 21738608
TI  - Cranial ontogeny in Stegoceras validum (Dinosauria: Pachycephalosauria): a
      quantitative model of pachycephalosaur dome growth and variation.
AB  - Historically, studies of pachycephalosaurs have recognized plesiomorphically flat
      headed taxa and apomorphically domed taxa. More recently, it has been suggested
      that the expression of the frontoparietal dome is ontogenetic and derived from a
      flat-headed juvenile morphology. However, strong evidence to support this
      hypothesis has been lacking. Here we test this hypothesis in a large,
      stratigraphically constrained sample of specimens assigned to Stegoceras validum,
      the best known pachycephalosaur, using multiple independent lines of evidence
      including conserved morphology of ornamentation, landmark-based allometric
      analyses of frontoparietal shape, and cranial bone histology. New specimens show
      that the diagnostic ornamentation of the parietosquamosal bar is conserved
      throughout the size range of the sample, which links flat-headed specimens to
      domed S. validum. High-resolution CT scans of three frontoparietals reveal that
      vascularity decreases with size and document a pattern that is consistent with
      previously proposed histological changes during growth. Furthermore, aspects of
      dome shape and size are strongly correlated and indicative of ontogenetic growth.
      These results are complementary and strongly support the hypothesis that the
      sample represents a growth series of a single taxon. Cranial dome growth is
      positively allometric, proceeds from a flat-headed to a domed state, and confirms
      the synonymy of Ornatotholus browni as a juvenile Stegoceras. This dataset serves
      as the first detailed model of growth and variation in a pachycephalosaur. Flat
      headed juveniles possess three characters (externally open cranial sutures,
      tuberculate dorsal surface texture, and open supratemporal fenestrae) that are
      reduced or eliminated during ontogeny. These characters also occur in putative
      flat-headed taxa, suggesting that they may also represent juveniles of domed
      taxa. However, open cranial sutures and supratemporal fenestrae are plesiomorphic
      within Ornithischia, and thus should be expected in the adult stage of a
      primitive pachycephalosaur. Additional lines of evidence will be needed to
      resolve the taxonomic validity of flat-headed pachycephalosaur taxa.

PMID- 21738609
TI  - Dissemination of drinking water contamination data to consumers: a systematic
      review of impact on consumer behaviors.
AB  - BACKGROUND: Drinking water contaminated by chemicals or pathogens is a major
      public health threat in the developing world. Responses to this threat often
      require water consumers (households or communities) to improve their own
      management or treatment of water. One approach hypothesized to increase such
      positive behaviors is increasing knowledge of the risks of unsafe water through
      the dissemination of water contamination data. This paper reviews the evidence
      for this approach in changing behavior and subsequent health outcomes.
      METHODS/PRINCIPAL FINDINGS: A systematic review was conducted for studies where
      results of tests for contaminants in drinking water were disseminated to
      populations whose water supply posed a known health risk. Studies of any design
      were included where data were available from a contemporaneous comparison or
      control group. Using multiple sources >14,000 documents were located. Six studies
      met inclusion criteria (four of arsenic contamination and two of microbiological
      contamination). Meta-analysis was not possible in most cases due to heterogeneity
      of outcomes and study designs. Outcomes included water quality, change of water
      source, treatment of water, knowledge of contamination, and urinary arsenic.
      Source switching was most frequently reported: of 5 reporting studies 4 report
      significantly higher rates of switching (26-72%) among those who received a
      positive test result and a pooled risk difference was calculate for 2 studies (RD
      = 0.43 [CI0.4.0-0.46] 6-12 months post intervention) suggesting 43% more of those
      with unsafe wells switched source compared to those with safe wells. Strength of
      evidence is low since the comparison is between non-equivalent groups. Two
      studies concerning fecal contamination reported non-significant increases in
      point-of-use water treatment. CONCLUSION: Despite the publication of some large
      cohort studies and some encouraging results the evidence base to support
      dissemination of contamination data to improve water management is currently
      equivocal. Rigorous studies on this topic are needed, ideally using common
      outcome measures.

PMID- 21738610
TI  - Data sharing by scientists: practices and perceptions.
AB  - BACKGROUND: Scientific research in the 21st century is more data intensive and
      collaborative than in the past. It is important to study the data practices of
      researchers--data accessibility, discovery, re-use, preservation and,
      particularly, data sharing. Data sharing is a valuable part of the scientific
      method allowing for verification of results and extending research from prior
      results. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1329 scientists participated
      in this survey exploring current data sharing practices and perceptions of the
      barriers and enablers of data sharing. Scientists do not make their data
      electronically available to others for various reasons, including insufficient
      time and lack of funding. Most respondents are satisfied with their current
      processes for the initial and short-term parts of the data or research lifecycle
      (collecting their research data; searching for, describing or cataloging,
      analyzing, and short-term storage of their data) but are not satisfied with long
      term data preservation. Many organizations do not provide support to their
      researchers for data management both in the short- and long-term. If certain
      conditions are met (such as formal citation and sharing reprints) respondents
      agree they are willing to share their data. There are also significant
      differences and approaches in data management practices based on primary funding
      agency, subject discipline, age, work focus, and world region.
      CONCLUSIONS/SIGNIFICANCE: Barriers to effective data sharing and preservation are
      deeply rooted in the practices and culture of the research process as well as the
      researchers themselves. New mandates for data management plans from NSF and other
      federal agencies and world-wide attention to the need to share and preserve data
      could lead to changes. Large scale programs, such as the NSF-sponsored DataNET
      (including projects like DataONE) will both bring attention and resources to the
      issue and make it easier for scientists to apply sound data management
      principles.

PMID- 21738611
TI  - B vitamins, methionine and alcohol intake and risk of colon cancer in relation to
      BRAF mutation and CpG island methylator phenotype (CIMP).
AB  - BACKGROUND: One-carbon metabolism appears to play an important role in DNA
      methylation reaction. Evidence suggests that a low intake of B vitamins or high
      alcohol consumption increases colorectal cancer risk. How one-carbon nutrients
      affect the CpG island methylator phenotype (CIMP) or BRAF mutation status in
      colon cancer remains uncertain. METHODS: Utilizing incident colon cancers in a
      large prospective cohort of women (the Nurses' Health Study), we determined BRAF
      status (N = 386) and CIMP status (N = 375) by 8 CIMP-specific markers [CACNA1G,
      CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1], and 8 other CpG
      islands (CHFR, HIC1, IGFBP3, MGMT, MINT-1, MINT-31, p14, and WRN). We examined
      the relationship between intake of one-carbon nutrients and alcohol and colon
      cancer risk, by BRAF mutation or CIMP status. RESULTS: Higher folate intake was
      associated with a trend towards low risk of CIMP-low/0 tumors [total folate
      intake >=400 ug/day vs. <200 ug/day; the multivariate relative risk = 0.73; 95%
      CI = 0.53-1.02], whereas total folate intake had no influence on CIMP-high tumor
      risks (P(heterogeneity) = 0.73). Neither vitamin B(6), methionine or alcohol
      intake appeared to differentially influence risks for CIMP-high and CIMP-low/0
      tumors. Using the 16-marker CIMP panel did not substantially alter our results. B
      vitamins, methionine or alcohol intake did not affect colon cancer risk
      differentially by BRAF status. CONCLUSIONS: This molecular pathological
      epidemiology study suggests that low level intake of folate may be associated
      with an increased risk of CIMP-low/0 colon tumors, but not that of CIMP-high
      tumors. However, the difference between CIMP-high and CIMP-low/0 cancer risks was
      not statistically significant, and additional studies are necessary to confirm
      these observations.

PMID- 21738612
TI  - Overexpression of Nrdp1 in the heart exacerbates doxorubicin-induced cardiac
      dysfunction in mice.
AB  - BACKGROUND: Cardiac cell death and generation of oxidative stress contribute to
      doxorubicin (DOX)-induced cardiac dysfunction. E3 ligase Nrdp1 plays a critical
      role in the regulation of cell apoptosis, inflammation and production of reactive
      oxygen species (ROS), which may contribute to heart failure. However, the role of
      Nrdp1 in DOX-induced cardiac injury remains to be determined. METHODS AND
      RESULTS: We examined the effect of Nrdp1 overexpression with DOX treatment in rat
      neonatal cardiomyocytes and mouse heart tissue. Cardiomyocytes were infected with
      adenovirus containing GFP (Ad-GFP), Nrdp1 wild-type (Ad-Nrdp1) or the dominant
      negative form of Nrdp1 (Ad-Dn-Nrdp1), then treated with DOX for 24 hr. DOX
      treatment increased cell death and apoptosis, with Ad-Nrdp1 infection enhancing
      these actions but Ad-Dn-Nrdp1 infection attenuating these effects. Furthermore, 5
      days after a single injection of DOX (20 mg/kg, intraperitoneally), Nrdp1
      transgenic mice (TG) showed decreased cardiac function and increased apoptosis,
      autophagy and oxidative stress as compared with wild-type (WT) mice (P<0.01).
      Survival rate was significantly lower in Nrdp1 TG mice than in WT mice 10 days
      after DOX injection (P<0.01). CONCLUSIONS/SIGNIFICANCE: These results were
      associated with decreased activation of Akt, extracellular signal-regulated
      kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3
      (STAT3) signaling pathways. Nrdp1 may be a key mediator in the development of
      cardiac dysfunction after DOX treatment and associated with inhibition of Akt,
      ERK1/2 and STAT3. Nrdp1 may be a new therapeutic target in protecting against the
      cardiotoxic effects of DOX.

PMID- 21738613
TI  - Extrapolation of urn models via poissonization: accurate measurements of the
      microbial unknown.
AB  - The availability of high-throughput parallel methods for sequencing microbial
      communities is increasing our knowledge of the microbial world at an
      unprecedented rate. Though most attention has focused on determining lower-bounds
      on the alpha-diversity i.e. the total number of different species present in the
      environment, tight bounds on this quantity may be highly uncertain because a
      small fraction of the environment could be composed of a vast number of different
      species. To better assess what remains unknown, we propose instead to predict the
      fraction of the environment that belongs to unsampled classes. Modeling samples
      as draws with replacement of colored balls from an urn with an unknown
      composition, and under the sole assumption that there are still undiscovered
      species, we show that conditionally unbiased predictors and exact prediction
      intervals (of constant length in logarithmic scale) are possible for the fraction
      of the environment that belongs to unsampled classes. Our predictions are based
      on a poissonization argument, which we have implemented in what we call the
      Embedding algorithm. In fixed i.e. non-randomized sample sizes, the algorithm
      leads to very accurate predictions on a sub-sample of the original sample. We
      quantify the effect of fixed sample sizes on our prediction intervals and test
      our methods and others found in the literature against simulated environments,
      which we devise taking into account datasets from a human-gut and -hand
      microbiota. Our methodology applies to any dataset that can be conceptualized as
      a sample with replacement from an urn. In particular, it could be applied, for
      example, to quantify the proportion of all the unseen solutions to a binding site
      problem in a random RNA pool, or to reassess the surveillance of a certain
      terrorist group, predicting the conditional probability that it deploys a new
      tactic in a next attack.

PMID- 21738614
TI  - Vitamin A and retinoid derivatives for lung cancer: a systematic review and meta
      analysis.
AB  - BACKGROUND: Despite reported antiproliferative activity of vitamin A and its
      common use for cancer, there is no comprehensive synthesis of its safety and
      efficacy in lung cancers. To address this issue we conducted a systematic review
      of the safety and efficacy of vitamin A for the treatment and prevention of lung
      cancers. METHODS AND FINDINGS: Two independent reviewers searched six electronic
      databases from inception to July 2009 for clinical, observational, and
      preclinical evidence pertaining to the safety and efficacy of vitamin A and
      related retinoids for lung cancers. 248 studies were included for full review and
      analysis. Five RCTs assessed treatment of lung cancers, three assessed primary
      prevention, and three looked at secondary prevention of lung cancers. Five
      surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies
      were also included. 107 studies were included for interactions between vitamin A
      and chemo- or radiation-therapy. Although some studies demonstrated benefits,
      there was insufficient evidence overall to support the use of vitamin A or
      related retinoids for the treatment or prevention of lung cancers. Retinyl
      palmitate combined with beta carotene increased risk of lung cancer in smokers in
      the large CARET trial. Pooling of three studies pertaining to treatment and three
      studies on secondary prevention revealed no significant effects on response rate,
      second primary tumor, recurrence, 5-year survival, and mortality. There was a
      small improvement in event free survival associated with vitamin A compared to
      controls, RR 1.24 (95% CI 1.13-1.35). The synthetic rexinoid bexarotene increased
      survival significantly among a subset of patients in two RCTs (p<0.014, <0.087).
      CONCLUSIONS: There is a lack of evidence to support the use of naturally
      occurring retinoids for the treatment and prevention of lung cancers. The
      rexinoid bexarotene may hold promise for use among a subset of patients, and
      deserves further study.

PMID- 21738615
TI  - Scents of adolescence: the maturation of the olfactory phenotype in a free
      ranging mammal.
AB  - Olfaction is an important sensory modality for mate recognition in many mammal
      species. Odorants provide information about the health status, genotype,
      dominance status and/or reproductive status. How and when odor profiles change
      during sexual maturation is, however often unclear, particularly in free-ranging
      mammals. Here, we investigated whether the wing sac odorant of male greater sac
      winged bats (Saccopteryx bilineata, Emballonuridae) differs between young and
      adults, and thus offers information about sexual maturity to potential mating
      partners. Using gas chromatography-mass spectrometry, we found differences in the
      odorants of young and adult males prior and during, but not after the mating
      period. The wing sac odorant of adult males consists of several substances, such
      as Pyrocoll, 2,6,10-trimethyl-3-oxo-6,10-dodecadienolide, and a so far
      unidentified substance; all being absent in the odor profiles of juveniles prior
      to the mating season. During the mating season, these substances are present in
      most of the juvenile odorants, but still at lower quantities compared to the wing
      sac odorants of adults. These results suggest that the wing sac odorant of males
      encodes information about age and/or sexual maturity. Although female S.
      bilineata start to reproduce at the age of half a year, most males of the same
      age postpone the sexual maturation of their olfactory phenotype until after the
      first mating season.

PMID- 21738616
TI  - Role of physical bolus properties as sensory inputs in the trigger of swallowing.
AB  - BACKGROUND: Swallowing is triggered when a food bolus being prepared by
      mastication has reached a defined state. However, although this view is
      consensual and well supported, the physical properties of the swallowable bolus
      have been under-researched. We tested the hypothesis that measuring bolus
      physical changes during the masticatory sequence to deglutition would reveal the
      bolus properties potentially involved in swallowing initiation. METHODS: Twenty
      normo-dentate young adults were instructed to chew portions of cereal and spit
      out the boluses at different times in the masticatory sequence. The mechanical
      properties of the collected boluses were measured by a texture profile analysis
      test currently used in food science. The median particle size of the boluses was
      evaluated by sieving. In a simultaneous sensory study, twenty-five other subjects
      expressed their perception of bolus texture dominating at any mastication time.
      FINDINGS: Several physical changes appeared in the food bolus as it was formed
      during mastication: (1) in rheological terms, bolus hardness rapidly decreased as
      the masticatory sequence progressed, (2) by contrast, adhesiveness, springiness
      and cohesiveness regularly increased until the time of swallowing, (3) median
      particle size, indicating the bolus particle size distribution, decreased mostly
      during the first third of the masticatory sequence, (4) except for hardness, the
      rheological changes still appeared in the boluses collected just before
      swallowing, and (5) physical changes occurred, with sensory stickiness being
      described by the subjects as a dominant perception of the bolus at the end of
      mastication. CONCLUSIONS: Although these physical and sensory changes progressed
      in the course of mastication, those observed just before swallowing seem to be
      involved in swallowing initiation. They can be considered as strong candidates
      for sensory inputs from the bolus that are probably crucially involved in the
      triggering of swallowing, since they appeared in boluses prepared in various
      mastication strategies by different subjects.

PMID- 21738617
TI  - Bone marrow mononuclear cells up-regulate toll-like receptor expression and
      produce inflammatory mediators in response to cigarette smoke extract.
AB  - Several reports link cigarette smoking with leukemia. However, the effects of
      cigarette smoke extract (CSE) on bone marrow hematopoiesis remain unknown. The
      objective of this study was to elucidate the direct effects of cigarette smoke on
      human bone marrow hematopoiesis and characterize the inflammatory process known
      to result from cigarette smoking. Bone marrow mononuclear cells (BMCs) from
      healthy individuals when exposed to CSE had significantly diminished CFU-E, BFU-E
      and CFU-GM. We found increased nuclear translocation of the NF-kappaB p65 subunit
      and, independently, enhanced activation of AKT and ERK1/2. Exposure of BMCs to
      CSE induced IL-8 and TGF-beta1 production, which was dependent on NF-kappaB and
      ERK1/2, but not on AKT. CSE treatment had no effect on the release of TNF-alpha,
      IL-10, or VEGF. Finally, CSE also had a significant induction of TLR2, TLR3 and
      TLR4, out of which, the up-regulation of TLR2 and TLR3 was found to be dependent
      on ERK1/2 and NF-kappaB activation, but not AKT. These results indicate that CSE
      profoundly inhibits the growth of erythroid and granulocyte-macrophage
      progenitors in the bone marrow. Further, CSE modulates NF-kappaB- and ERK1/2
      dependent responses, suggesting that cigarette smoking may impair bone marrow
      hematopoiesis in vivo as well as induce inflammation, two processes that proceed
      malignant transformation.

PMID- 21738618
TI  - Gender differences in healthy ranges for serum alanine aminotransferase levels in
      adolescence.
AB  - BACKGROUND & AIMS: There is a worldwide epidemic of obesity among adolescents who
      subsequently are at increased risk for the development of non alcoholic fatty
      liver disease (NAFLD). The serum alanine aminotransferase (ALT) is the most
      frequently used test for screening these individuals, but no age and gender
      specific upper limits of normal (ULN) based on healthy population data in
      children are available. The objective of the present study was to define ULN for
      ALT in healthy children in order to use this as a tool for case finding. METHODS:
      A total of 975 school children (aged 7-18 years) were included in the study
      cohort. Highly significant correlations (all p<0.001) were noted between ALT
      values and measures of BMI, systolic and diastolic blood pressure, insulin
      levels, HOMA-IR, total cholesterol and triglyceride concentrations. In order to
      define the population with no risk factors, we excluded subjects having abnormal
      values for factors that correlated with ALT. This population comprised 186 boys
      and 185 girls. RESULTS: In boys, median serum ALT levels were 16 IU/L and 9, 11,
      18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles. In girls, median
      serum ALT was 13, and 7, 9, 16, and 21 IU/L for the 5th, 25th, 75th, and 95th
      percentiles, respectively. The ULNs for ALT were 30 IU/L and 21 IU/L for boys and
      girls respectively. We found a linear relationship between age and ALT in females
      (p<0.001) but not in males. By multiple logistic regression, independent
      predictors of an elevated ALT included the BMI, waist hip ratio and levels of
      serum total cholesterol. In females, age was an additional inverse predictor.
      CONCLUSIONS: In children and adolescents, these normal limits for ALT should be
      applied. Those with persistent elevations should be investigated further.

PMID- 21738619
TI  - Rescue of photoreceptor degeneration by curcumin in transgenic rats with P23H
      rhodopsin mutation.
AB  - The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered
      trafficking and formation of insoluble aggregates leading to photoreceptor
      degeneration and autosomal dominant retinitis pigmentosa (RP). There are no
      effective therapies to treat this condition. Compounds that enhance dissociation
      of protein aggregates may be of value in developing new treatments for such
      diseases. Anti-protein aggregating activity of curcumin has been reported
      earlier. In this study we present that treatment of COS-7 cells expressing mutant
      rhodopsin with curcumin results in dissociation of mutant protein aggregates and
      decreases endoplasmic reticulum stress. Furthermore we demonstrate that
      administration of curcumin to P23H-rhodopsin transgenic rats improves retinal
      morphology, physiology, gene expression and localization of rhodopsin. Our
      findings indicate that supplementation of curcumin improves retinal structure and
      function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin
      may serve as a potential therapeutic agent in treating RP due to the P23H
      rhodopsin mutation and perhaps other degenerative diseases caused by protein
      trafficking defects.

PMID- 21738620
TI  - Leaders in social networks, the Delicious case.
AB  - Finding pertinent information is not limited to search engines. Online
      communities can amplify the influence of a small number of power users for the
      benefit of all other users. Users' information foraging in depth and breadth can
      be greatly enhanced by choosing suitable leaders. For instance in delicious.com,
      users subscribe to leaders' collection which lead to a deeper and wider reach not
      achievable with search engines. To consolidate such collective search, it is
      essential to utilize the leadership topology and identify influential users.
      Google's PageRank, as a successful search algorithm in the World Wide Web, turns
      out to be less effective in networks of people. We thus devise an adaptive and
      parameter-free algorithm, the LeaderRank, to quantify user influence. We show
      that LeaderRank outperforms PageRank in terms of ranking effectiveness, as well
      as robustness against manipulations and noisy data. These results suggest that
      leaders who are aware of their clout may reinforce the development of social
      networks, and thus the power of collective search.

PMID- 21738621
TI  - The first molecular phylogeny of Strepsiptera (Insecta) reveals an early burst of
      molecular evolution correlated with the transition to endoparasitism.
AB  - A comprehensive model of evolution requires an understanding of the relationship
      between selection at the molecular and phenotypic level. We investigate this in
      Strepsiptera, an order of endoparasitic insects whose evolutionary biology is
      poorly studied. We present the first molecular phylogeny of Strepsiptera, and use
      this as a framework to investigate the association between parasitism and
      molecular evolution. We find evidence of a significant burst in the rate of
      molecular evolution in the early history of Strepsiptera. The evolution of
      morphological traits linked to parasitism is significantly correlated with the
      pattern in molecular rate. The correlated burst in genotypic-phenotypic evolution
      precedes the main phase of strepsipteran diversification, which is characterised
      by the return to a low and even molecular rate, and a period of relative
      morphological stability. These findings suggest that the transition to
      endoparasitism led to relaxation of selective constraint in the strepsipteran
      genome. Our results indicate that a parasitic lifestyle can affect the rate of
      molecular evolution, although other causal life-history traits correlated with
      parasitism may also play an important role.

PMID- 21738622
TI  - Escitalopram and neuroendocrine response in healthy first-degree relatives to
      depressed patients--a randomized placebo-controlled trial.
AB  - INTRODUCTION: The mechanisms by which selective serotonin re-uptake inhibitors
      (SSRI) act in depressed patients remain unknown. The serotonergic
      neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may
      interact. The aim of the AGENDA trial was to investigate whether long-term
      intervention with SSRI versus placebo affects the cortisol response in the
      dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first
      degree relatives to patients with major depressive disorder (MDD). METHODS:
      Eighty healthy first-degree relatives to patients with MDD were randomized to
      escitalopram 10 mg versus matching placebo daily for four weeks. The primary
      outcome measure was the intervention difference in the change of the total area
      under the curve (CorAUC(total)) for plasma cortisol in the DEX-CRH test at entry
      to after four weeks of intervention. RESULTS: Change in CorAUC(total) showed no
      statistically significant difference between the escitalopram and the placebo
      group, p = 0.47. There were large intra- and inter-individual differences in the
      results of the DEX-CRH test. There was statistically significant negative
      correlation between the plasma escitalopram concentration and change in
      CorAUC(total), rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically
      significant interaction between age and intervention group and change in log
      CorAUC(total). CONCLUSION: The present trial does not support an effect of
      escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first
      degree relatives to patients with MDD. Increasing levels of escitalopram tended
      to decrease the HPA-response in the DEX-CRH test and this effect increased with
      age. TRIAL REGISTRATION: ClinicalTrials.gov NCT00386841.

PMID- 21738623
TI  - Fisetin lowers methylglyoxal dependent protein glycation and limits the
      complications of diabetes.
AB  - The elevated glycation of macromolecules by the reactive dicarbonyl and alpha
      oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its
      complications. We have identified a rare flavone, fisetin, which increases the
      level and activity of glyoxalase 1, the enzyme required for the removal of MG, as
      well as the synthesis of its essential co-factor, glutathione. It is shown that
      fisetin reduces two major complications of diabetes in Akita mice, a model of
      type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar,
      it reduced kidney hypertrophy and albuminuria and maintained normal levels of
      locomotion in the open field test. This correlated with a reduction in proteins
      glycated by MG in the blood, kidney and brain of fisetin-treated animals along
      with an increase in glyoxalase 1 enzyme activity and an elevation in the
      expression of the rate-limiting enzyme for the synthesis of glutathione, a co
      factor for glyoxalase 1. The expression of the receptor for advanced glycation
      end products (RAGE), serum amyloid A and serum C-reactive protein, markers of
      protein oxidation, glycation and inflammation, were also increased in diabetic
      Akita mice and reduced by fisetin. It is concluded that fisetin lowers the
      elevation of MG-protein glycation that is associated with diabetes and
      ameliorates multiple complications of the disease. Therefore, fisetin or a
      synthetic derivative may have potential therapeutic use for the treatment of
      diabetic complications.

PMID- 21738624
TI  - The blood of healthy individuals exhibits CD8 T cells with a highly altered TCR
      Vb repertoire but with an unmodified phenotype.
AB  - CD8 T cell clonal expansions (TCE) have been observed in elderly, healthy
      individuals as well in old mice, and have been associated with the ageing
      process. Both chronic latent and non-persistent viral infections have been
      proposed to drive the development of distinct non-functional and functional TCE
      respectively. Biases in TCR Vbeta repertoire diversity are also recurrently
      observed in patients that have undergone strong immune challenge, and are
      preferentially observed in the CD8 compartment. Healthy adults can also exhibit
      CD8 T cells with strong alterations of their CDR3 length distribution.
      Surprisingly, no specific investigations have been conducted to analyze the CD8 T
      cell repertoire in normal adults, to determine if such alterations in TCR Vbeta
      repertoire share the features of TCE. In this study, we characterized the
      phenotype and function of the CD8 population in healthy individuals of 25-52
      years of age. All but one of the EBV-positive HLA-B8 healthy volunteers that were
      studied were CMV-negative. Using a specific unsupervised statistical method, we
      identified Vbeta families with altered CDR3 length distribution and increased TCR
      Vbeta/HPRT transcript ratios in all individuals tested. The increase in TCR
      Vbeta/HPRT transcript ratio was more frequently associated with an increase in
      the percentage of the corresponding Vbeta(+) T cells than with an absence of
      modification of their percentage. However, in contrast with the previously
      described TCE, these CD8(+) T cells were not preferentially found in the memory
      CD8 subset, they exhibited normal effector functions (cytokine secretion and
      cytotoxic molecule expression) and they were not reactive to a pool of
      EBV/CMV/Flu virus peptides. Taken together, the combined analysis of transcripts
      and proteins of the TCR Vbeta repertoire led to the identification of different
      types of CD8(+) T cell clone expansion or contraction in healthy individuals, a
      situation that appears more complex than previously described in aged
      individuals.

PMID- 21738625
TI  - To clone or not to clone: method analysis for retrieving consensus sequences in
      ancient DNA samples.
AB  - The challenges associated with the retrieval and authentication of ancient DNA
      (aDNA) evidence are principally due to post-mortem damage which makes ancient
      samples particularly prone to contamination from "modern" DNA sources. The
      necessity for authentication of results has led many aDNA researchers to adopt
      methods considered to be "gold standards" in the field, including cloning aDNA
      amplicons as opposed to directly sequencing them. However, no standardized
      protocol has emerged regarding the necessary number of clones to sequence, how a
      consensus sequence is most appropriately derived, or how results should be
      reported in the literature. In addition, there has been no systematic
      demonstration of the degree to which direct sequences are affected by damage or
      whether direct sequencing would provide disparate results from a consensus of
      clones.To address this issue, a comparative study was designed to examine both
      cloned and direct sequences amplified from ~3,500 year-old ancient northern fur
      seal DNA extracts. Majority rules and the Consensus Confidence Program were used
      to generate consensus sequences for each individual from the cloned sequences,
      which exhibited damage at 31 of 139 base pairs across all clones. In no instance
      did the consensus of clones differ from the direct sequence. This study
      demonstrates that, when appropriate, cloning need not be the default method, but
      instead, should be used as a measure of authentication on a case-by-case basis,
      especially when this practice adds time and cost to studies where it may be
      superfluous.

PMID- 21738626
TI  - Neuronal spike train analysis in likelihood space.
AB  - BACKGROUND: Conventional methods for spike train analysis are predominantly based
      on the rate function. Additionally, many experiments have utilized a temporal
      coding mechanism. Several techniques have been used for analyzing these two
      sources of information separately, but using both sources in a single framework
      remains a challenging problem. Here, an innovative technique is proposed for
      spike train analysis that considers both rate and temporal information.
      METHODOLOGY/PRINCIPAL FINDINGS: Point process modeling approach is used to
      estimate the stimulus conditional distribution, based on observation of repeated
      trials. The extended Kalman filter is applied for estimation of the parameters in
      a parametric model. The marked point process strategy is used in order to extend
      this model from a single neuron to an entire neuronal population. Each spike
      train is transformed into a binary vector and then projected from the observation
      space onto the likelihood space. This projection generates a newly structured
      space that integrates temporal and rate information, thus improving performance
      of distribution-based classifiers. In this space, the stimulus-specific
      information is used as a distance metric between two stimuli. To illustrate the
      advantages of the proposed technique, spiking activity of inferior temporal
      cortex neurons in the macaque monkey are analyzed in both the observation and
      likelihood spaces. Based on goodness-of-fit, performance of the estimation method
      is demonstrated and the results are subsequently compared with the firing rate
      based framework. CONCLUSIONS/SIGNIFICANCE: From both rate and temporal
      information integration and improvement in the neural discrimination of stimuli,
      it may be concluded that the likelihood space generates a more accurate
      representation of stimulus space. Further, an understanding of the neuronal
      mechanism devoted to visual object categorization may be addressed in this
      framework as well.

PMID- 21738627
TI  - Forest fruit production is higher on Sumatra than on Borneo.
AB  - BACKGROUND: Various studies have shown that the population densities of a number
      of forest vertebrates, such as orangutans, are higher on Sumatra than Borneo, and
      that several species exhibit smaller body sizes on Borneo than Sumatra and
      mainland Southeast Asia. It has been suggested that differences in forest fruit
      productivity between the islands can explain these patterns. Here we present a
      large-scale comparison of forest fruit production between the islands to test
      this hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Data on fruit production were
      collated from Sumatran and Bornean sites. At six sites we assessed fruit
      production in three forest types: riverine, peat swamp and dryland forests. We
      compared fruit production using time-series models during different periods of
      overall fruit production and in different tree size classes. We examined overall
      island differences and differences specifically for fruiting period and tree size
      class. The results of these analyses indicate that overall the Sumatran forests
      are more productive than those on Borneo. This difference remains when each of
      the three forest types (dryland, riverine, and peat) are examined separately. The
      difference also holds over most tree sizes and fruiting periods.
      CONCLUSIONS/SIGNIFICANCE: Our results provide strong support for the hypothesis
      that forest fruit productivity is higher on Sumatra than Borneo. This difference
      is most likely the result of the overall younger and more volcanic soils on
      Sumatra than Borneo. These results contribute to our understanding of the
      determinants of faunal density and the evolution of body size on both islands.

PMID- 21738628
TI  - CO2 efflux from cleared mangrove peat.
AB  - BACKGROUND: CO(2) emissions from cleared mangrove areas may be substantial,
      increasing the costs of continued losses of these ecosystems, particularly in
      mangroves that have highly organic soils. METHODOLOGY/PRINCIPAL FINDINGS: We
      measured CO(2) efflux from mangrove soils that had been cleared for up to 20
      years on the islands of Twin Cays, Belize. We also disturbed these cleared peat
      soils to assess what disturbance of soils after clearing may have on CO(2)
      efflux. CO(2) efflux from soils declines from time of clearing from ~10,600
      tonnes km(-2) year(-1) in the first year to 3000 tonnes km(2) year(-1) after 20
      years since clearing. Disturbing peat leads to short term increases in CO(2)
      efflux (27 umol m(-2) s(-1)), but this had returned to baseline levels within 2
      days. CONCLUSIONS/SIGNIFICANCE: Deforesting mangroves that grow on peat soils
      results in CO(2) emissions that are comparable to rates estimated for peat
      collapse in other tropical ecosystems. Preventing deforestation presents an
      opportunity for countries to benefit from carbon payments for preservation of
      threatened carbon stocks.

PMID- 21738629
TI  - Intercellular communication by exchange of cytoplasmic material via tunneling
      nano-tube like structures in primary human renal epithelial cells.
AB  - Transfer of cellular material via tunneling nanotubes (TNT) was recently
      discovered as a novel mechanism for intercellular communication. The role of
      intercellular exchange in communication of renal epithelium is not known. Here we
      report extensive spontaneous intercellular exchange of cargo vesicles and
      organelles between primary human proximal tubular epithelial cells (RPTEC). Cells
      were labeled with two different quantum dot nanocrystals (Qtracker 605 or 525)
      and intercellular exchange was quantified by high-throughput fluorescence imaging
      and FACS analysis. In co-culture, a substantial fraction of cells (67.5%)
      contained both dyes indicating high levels of spontaneous intercellular exchange
      in RPTEC. The double positive cells could be divided into three categories based
      on the preponderance of 605 Qtracker (46.30%), 525 Qtracker (48.3%) and
      approximately equal content of both Qtrackers (4.57%). The transfer of
      mitochondria between RPTECs was also detected using an organelle specific dye.
      Inhibition of TNT genesis by actin polymerization inhibitor (Latrunculin B)
      markedly reduced intercellular exchange (>60%) suggesting that intercellular
      exchange in RPTEC was in part mediated via TNT-like structures. In contrast,
      induction of cellular stress by Zeocin treatment increased tube-genesis in RPTEC.
      Our data indicates an unexpected dynamic of intercellular communication between
      RPTEC by exchange of cytosolic material, which may play an important role in
      renal physiology.

PMID- 21738630
TI  - Computational analysis of the spatiotemporal coordination of polarized PI3K and
      Rac1 activities in micro-patterned live cells.
AB  - Polarized molecular activities play important roles in guiding the cell toward
      persistent and directional migration. In this study, the polarized distributions
      of the activities of phosphatidylinositol 3-kinase (PI3K) and the Rac1 small
      GTPase were monitored using chimeric fluorescent proteins (FPs) in cells
      constrained on micro-patterned strips, with one end connecting to a neighboring
      cell (junction end) and the other end free of cell-cell contact (free end). The
      recorded spatiotemporal dynamics of the fluorescent intensity from different
      cells was scaled into a uniform coordinate system and applied to compute the
      molecular activity landscapes in space and time. The results revealed different
      polarization patterns of PI3K and Rac1 activity induced by the growth factor
      stimulation. The maximal intensity of different FPs, and the edge position and
      velocity at the free end were further quantified to analyze their correlation and
      decipher the underlying signaling sequence. The results suggest that the
      initiation of the edge extension occurred before the activation of PI3K, which
      led to a stable extension of the free end followed by the Rac1 activation.
      Therefore, the results support a concerted coordination of sequential signaling
      events and edge dynamics, underscoring the important roles played by PI3K
      activity at the free end in regulating the stable lamellipodia extension and cell
      migration. Meanwhile, the quantification methods and accompanying software
      developed can provide a convenient and powerful computational analysis platform
      for the study of spatiotemporal molecular distribution and hierarchy in live
      cells based on fluorescence images.

PMID- 21738631
TI  - A PTG variant contributes to a milder phenotype in Lafora disease.
AB  - Lafora disease is an autosomal recessive form of progressive myoclonus epilepsy
      with no effective therapy. Although the outcome is always unfavorable, onset of
      symptoms and progression of the disease may vary. We aimed to identify modifier
      genes that may contribute to the clinical course of Lafora disease patients with
      EPM2A or EPM2B mutations. We established a list of 43 genes coding for proteins
      related to laforin/malin function and/or glycogen metabolism and tested common
      polymorphisms for possible associations with phenotypic differences using a
      collection of Lafora disease families. Genotype and haplotype analysis showed
      that PPP1R3C may be associated with a slow progression of the disease. The
      PPP1R3C gene encodes protein targeting to glycogen (PTG). Glycogen targeting
      subunits play a major role in recruiting type 1 protein phosphatase (PP1) to
      glycogen-enriched cell compartments and in increasing the specific activity of
      PP1 toward specific glycogenic substrates (glycogen synthase and glycogen
      phosphorylase). Here, we report a new mutation (c.746A>G, N249S) in the PPP1R3C
      gene that results in a decreased capacity to induce glycogen synthesis and a
      reduced interaction with glycogen phosphorylase and laforin, supporting a key
      role of this mutation in the glycogenic activity of PTG. This variant was found
      in one of two affected siblings of a Lafora disease family characterized by a
      remarkable mild course. Our findings suggest that variations in PTG may condition
      the course of Lafora disease and establish PTG as a potential target for
      pharmacogenetic and therapeutic approaches.

PMID- 21738632
TI  - Phylogenetic and biogeographic analysis of sphaerexochine trilobites.
AB  - BACKGROUND: Sphaerexochinae is a speciose and widely distributed group of
      cheirurid trilobites. Their temporal range extends from the earliest Ordovician
      through the Silurian, and they survived the end Ordovician mass extinction event
      (the second largest mass extinction in Earth history). Prior to this study, the
      individual evolutionary relationships within the group had yet to be determined
      utilizing rigorous phylogenetic methods. Understanding these evolutionary
      relationships is important for producing a stable classification of the group,
      and will be useful in elucidating the effects the end Ordovician mass extinction
      had on the evolutionary and biogeographic history of the group.
      METHODOLOGY/PRINCIPAL FINDINGS: Cladistic parsimony analysis of cheirurid
      trilobites assigned to the subfamily Sphaerexochinae was conducted to evaluate
      phylogenetic patterns and produce a hypothesis of relationship for the group.
      This study utilized the program TNT, and the analysis included thirty-one taxa
      and thirty-nine characters. The results of this analysis were then used in a
      Lieberman-modified Brooks Parsimony Analysis to analyze biogeographic patterns
      during the Ordovician-Silurian. CONCLUSIONS/SIGNIFICANCE: The genus Sphaerexochus
      was found to be monophyletic, consisting of two smaller clades (one composed
      entirely of Ordovician species and another composed of Silurian and Ordovician
      species). By contrast, the genus Kawina was found to be paraphyletic. It is a
      basal grade that also contains taxa formerly assigned to Cydonocephalus.
      Phylogenetic patterns suggest Sphaerexochinae is a relatively distinctive
      trilobite clade because it appears to have been largely unaffected by the end
      Ordovician mass extinction. Finally, the biogeographic analysis yields two major
      conclusions about Sphaerexochus biogeography: Bohemia and Avalonia were close
      enough during the Silurian to exchange taxa; and during the Ordovician there was
      dispersal between Eastern Laurentia and the Yangtze block (South China) and
      between Eastern Laurentia and Avalonia.

PMID- 21738633
TI  - Effect of investment in malaria control on child mortality in sub-Saharan Africa
      in 2002-2008.
AB  - BACKGROUND: Around 8.8 million children under-five die each year, mostly due to
      infectious diseases, including malaria that accounts for 16% of deaths in Africa,
      but the impact of international financing of malaria control on under-five
      mortality in sub-Saharan Africa has not been examined. METHODS AND FINDINGS: We
      combined multiple data sources and used panel data regression analysis to study
      the relationship among investment, service delivery/intervention coverage, and
      impact on child health by observing changes in 34 sub-Saharan African countries
      over 2002-2008. We used Lives Saved Tool to estimate the number of lives saved
      from coverage increase of insecticide-treated nets (ITNs)/indoor residual
      spraying (IRS). As an indicator of outcome, we also used under-five mortality
      rate. Global Fund investments comprised more than 70% of the Official Development
      Assistance (ODA) for malaria control in 34 countries. Each $1 million ODA for
      malaria enabled distribution of 50,478 ITNs [95%CI: 37,774-63,182] in the
      disbursement year. 1,000 additional ITNs distributed saved 0.625 lives [95%CI:
      0.369-0.881]. Cumulatively Global Fund investments that increased ITN/IRS
      coverage in 2002-2008 prevented an estimated 240,000 deaths. Countries with
      higher malaria burden received less ODA disbursement per person-at-risk compared
      to lower-burden countries ($3.90 vs. $7.05). Increased ITN/IRS coverage in high
      burden countries led to 3,575 lives saved per 1 million children, as compared
      with 914 lives in lower-burden countries. Impact of ITN/IRS coverage on under
      five mortality was significant among major child health interventions such as
      immunisation showing that 10% increase in households with ITN/IRS would reduce
      1.5 [95%CI: 0.3-2.8] child deaths per 1000 live births. CONCLUSIONS: Along with
      other key child survival interventions, increased ITNs/IRS coverage has
      significantly contributed to child mortality reduction since 2002. ITN/IRS scale
      up can be more efficiently prioritized to countries where malaria is a major
      cause of child deaths to save greater number of lives with available resources.

PMID- 21738634
TI  - Plasmodium falciparum malaria endemicity in Indonesia in 2010.
AB  - BACKGROUND: Malaria control programs require a detailed understanding of the
      contemporary spatial distribution of infection risk to efficiently allocate
      resources. We used model based geostatistics (MBG) techniques to generate a
      contemporary map of Plasmodium falciparum malaria risk in Indonesia in 2010.
      METHODS: Plasmodium falciparum Annual Parasite Incidence (PfAPI) data (2006-2008)
      were used to map limits of P. falciparum transmission. A total of 2,581 community
      blood surveys of P. falciparum parasite rate (PfPR) were identified (1985-2009).
      After quality control, 2,516 were included into a national database of age
      standardized 2-10 year old PfPR data (PfPR(2-10)) for endemicity mapping. A
      Bayesian MBG procedure was used to create a predicted surface of PfPR(2-10)
      endemicity with uncertainty estimates. Population at risk estimates were derived
      with reference to a 2010 human population count surface. RESULTS: We estimate
      132.8 million people in Indonesia, lived at risk of P. falciparum transmission in
      2010. Of these, 70.3% inhabited areas of unstable transmission and 29.7% in
      stable transmission. Among those exposed to stable risk, the vast majority were
      at low risk (93.39%) with the reminder at intermediate (6.6%) and high risk
      (0.01%). More people in western Indonesia lived in unstable rather than stable
      transmission zones. In contrast, fewer people in eastern Indonesia lived in
      unstable versus stable transmission areas. CONCLUSION: While further feasibility
      assessments will be required, the immediate prospects for sustained control are
      good across much of the archipelago and medium term plans to transition to the
      pre-elimination phase are not unrealistic for P. falciparum. Endemicity in areas
      of Papua will clearly present the greatest challenge. This P. falciparum
      endemicity map allows malaria control agencies and their partners to
      comprehensively assess the region-specific prospects for reaching pre
      elimination, monitor and evaluate the effectiveness of future strategies against
      this 2010 baseline and ultimately improve their evidence-based malaria control
      strategies.

PMID- 21738635
TI  - Characterisation of a desmosterol reductase involved in phytosterol dealkylation
      in the silkworm, Bombyx mori.
AB  - Most species of invertebrate animals cannot synthesise sterols de novo and many
      that feed on plants dealkylate phytosterols (mostly C(29) and C(28)) yielding
      cholesterol (C(27)). The final step of this dealkylation pathway involves
      desmosterol reductase (DHCR24)-catalysed reduction of desmosterol to cholesterol.
      We now report the molecular characterisation in the silkworm, Bombyx mori, of
      such a desmosterol reductase involved in production of cholesterol from
      phytosterol, rather than in de novo synthesis of cholesterol. Phylogenomic
      analysis of putative desmosterol reductases revealed the occurrence of various
      clades that allowed for the identification of a strong reductase candidate gene
      in Bombyx mori (BGIBMGA 005735). Following PCR-based cloning of the cDNA (1.6 kb)
      and its heterologous expression in Saccharomyces cerevisae, the recombinant
      protein catalysed reduction of desmosterol to cholesterol in an NADH- and FAD
      dependent reaction.Conceptual translation of the cDNA, that encodes a 58.9 kDa
      protein, and database searching, revealed that the enzyme belongs to an FAD
      dependent oxidoreductase family. Western blotting revealed reductase protein
      expression exclusively in the microsomal subcellular fraction and primarily in
      the gut. The protein is peripherally associated with microsomal membranes. 2D
      native gel and PAGE analysis revealed that the reductase is part of a large
      complex with molecular weight approximately 250 kDa. The protein occurs in midgut
      microsomes at a fairly constant level throughout development in the last two
      instars, but is drastically reduced during the wandering stage in preparation for
      metamorphosis. Putative Broad Complex transcription factor-binding sites
      detectable upstream of the DHCR24 gene may play a role in this down-regulation.

PMID- 21738636
TI  - Altered germination and subcellular localization patterns for PUB44/SAUL1 in
      response to stress and phytohormone treatments.
AB  - BACKGROUND: In plants, the ubiquitin-proteasome system is emerging as a
      significant regulatory system throughout the plant lifecycle. The ubiquitination
      of a target protein requires the sequential actions of the E1, E2 and E3 enzymes,
      with the latter E3 enzyme conferring target selection in this process. There are
      a large number of predicted E3 enzymes in plant genomes, and very little is known
      about the functions of many of these predicted genes. Here we report here an
      analysis of two closely-related members of the Arabidopsis Plant U-box (PUB)
      family of E3 ubiquitin ligases, PUB43 and PUB44. PRINCIPAL FINDINGS: Homozygous
      pub44/pub44 mutant seedlings were found displayed a seedling lethal phenotype and
      this corresponded with widespread cell death lesions throughout the cotyledons
      and roots. Interestingly, heterozygous PUB44/pub44 seedlings were wild-type in
      appearance yet displayed intermediate levels of cell death lesions in comparison
      to pub44/pub44 seedlings. In contrast, homozygous pub43/pub43 mutants were viable
      and did not show any signs of cell death despite the PUB43 gene being more highly
      expressed than PUB44. The PUB44 mutants are not classical lesion mimic mutants as
      they did not have increased resistance to plant pathogens. We also observed
      increased germination rates in mutant seeds for both PUB44 and PUB43 under
      inhibitory concentrations of abscisic acid. Finally, the subcellular localization
      of PUB44 was investigated with transient expression assays in BY-2 cells. Under
      varying conditions, PUB44 was observed to be localized to the cytoplasm, plasma
      membrane, or nucleus. CONCLUSIONS: Based on mutant plant analyses, the
      Arabidopsis PUB43 and PUB44 genes are proposed to function during seed
      germination and early seedling growth. Given PUB44's ability to shuttle from the
      nucleus to the plasma membrane, PUB44 may be active in different subcellular
      compartments as part of these biological functions.

PMID- 21738638
TI  - Cloning and characterization of porcine 4Ig-B7-H3: a potent inhibitor of porcine
      T-cell activation.
AB  - BACKGROUND: Members of the B7 superfamily costimulate the proliferation of
      lymphocytes during the initiation and maintenance of antigen-specific humoral and
      cell-mediated immune responses. B7-H3 (CD276) is a newly identified member of the
      B7 superfamily. It has been shown that B7-H3 plays a significant role in
      regulating T cell response in humans and mice, but it is not known whether a
      counterpart of human or murine B7-H3 exists in porcine species.
      METHODOLOGY/PRINCIPAL FINDINGS: We cloned the porcine 4ig-b7-h3 gene using a
      blast search at the NCBI database with human b7-h3, RT-PCR and 3'-terminus RACE.
      Protein sequence analysis showed that the protein encoded by this gene contained
      4Ig-like domains and was 90.88% identical with human 4Ig-B7-H3. Results of Dot
      blot hybridization and RT-PCR showed that B7-H3 was broadly distributed in
      porcine tissues mainly as two isoforms, 2Ig-B7-H3 and 4Ig-B7-H3, of which 4Ig-B7
      H3 was dominant. We further demonstrated that porcine 4Ig-B7-H3 was able to
      inhibit the proliferation and cytokine production of porcine T cells activated
      through the TCR pathway, similar to human B7-H3. CONCLUSION: We cloned the
      porcine 4ig-b7-h3 gene and demonstrated that the porcine 4Ig-B7-H3 serves as a
      negative regulator for the T-cell immune response.

PMID- 21738637
TI  - Functional stability of unliganded envelope glycoprotein spikes among isolates of
      human immunodeficiency virus type 1 (HIV-1).
AB  - The HIV-1 envelope glycoprotein (Env) spike is challenging to study at the
      molecular level, due in part to its genetic variability, structural heterogeneity
      and lability. However, the extent of lability in Env function, particularly for
      primary isolates across clades, has not been explored. Here, we probe stability
      of function for variant Envs of a range of isolates from chronic and acute
      infection, and from clades A, B and C, all on a constant virus backbone.
      Stability is elucidated in terms of the sensitivity of isolate infectivity to
      destabilizing conditions. A heat-gradient assay was used to determine T(90)
      values, the temperature at which HIV-1 infectivity is decreased by 90% in 1 h,
      which ranged between ~40 to 49 degrees C (n = 34). For select Envs (n = 10), the
      half-lives of infectivity decay at 37 degrees C were also determined and these
      correlated significantly with the T(90) (p = 0.029), though two 'outliers' were
      identified. Specificity in functional Env stability was also evident. For
      example, Env variant HIV-1(ADA) was found to be labile to heat, 37 degrees C
      decay, and guanidinium hydrochloride but not to urea or extremes of pH, when
      compared to its thermostable counterpart, HIV-1(JR-CSF). Blue native PAGE
      analyses revealed that Env-dependent viral inactivation preceded complete
      dissociation of Env trimers. The viral membrane and membrane-proximal external
      region (MPER) of gp41 were also shown to be important for maintaining trimer
      stability at physiological temperature. Overall, our results indicate that
      primary HIV-1 Envs can have diverse sensitivities to functional inactivation in
      vitro, including at physiological temperature, and suggest that parameters of
      functional Env stability may be helpful in the study and optimization of native
      Env mimetics and vaccines.

PMID- 21738639
TI  - Detection of intraepithelial and stromal Langerin and CCR5 positive cells in the
      human endometrium: potential targets for HIV infection.
AB  - Both the upper (endocervix and uterus) and lower (ectocervix and vagina) female
      genital tract mucosa are considered to be target sites for sexual transmission of
      HIV. There are a few reports on the T cell and antigen-presenting cell
      distribution in human endometrial tissue however, there is little known about the
      expression of the HIV co-receptor CCR5 and HIV-binding C-type lectin receptors on
      endometrial cell subsets. We therefore assessed endometrial tissue sections from
      HIV seronegative women undergoing hysterectomy of a benign and non-inflammatory
      cause for phenotypic characterization of potential HIV target cells and receptors
      by immunohistochemistry. Langerin was expressed on intraepithelial CD1a+CD4+ and
      CD11c+CD4+ Langerhans cells. Furthermore, CCR5+CD4+CD3+ T cells, DC
      SIGN+MR+CD11c+ myeloid dendritic cells and MR+CD68+ macrophages were found within
      or adjacent to the epithelium of the uterine lumen. In addition, occasional
      CD123+ BDCA-2+ plasmacytoid dendritic cells were detected deep in the endometrial
      stroma. Both T cells and several antigen-presenting cells were detected in
      lymphoid aggregate formations in close proximity to the epithelial lining. The
      finding of intraepithelial and stromal Langerin+ cells as well as CCR5+ CD4+ T
      cells is novel for human endometrium.

PMID- 21738640
TI  - Demography and dispersal ability of a threatened saproxylic beetle: a mark
      recapture study of the Rosalia Longicorn (Rosalia alpina).
AB  - The Rosalia longicorn or Alpine longhorn (Coleoptera: Cerambycidae) is an
      endangered and strictly protected icon of European saproxylic biodiversity.
      Despite its popularity, lack of information on its demography and mobility may
      compromise adoption of suitable conservation strategies. The beetle experienced
      marked retreat from NW part of its range; its single population survives N of the
      Alps and W of the Carpathians. The population inhabits several small patches of
      old beech forest on hill-tops of the Ralska Upland, Czech Republic. We performed
      mark-recapture study of the population and assessed its distribution pattern. Our
      results demonstrate the high mobility of the beetle, including dispersal between
      hills (up to 1.6 km). The system is thus interconnected; it contained ~2000 adult
      beetles in 2008. Estimated population densities were high, ranging between 42 and
      84 adult beetles/hectare a year. The population survives at a former military
      training ground despite long-term isolation and low cover of mature beech forest
      (~1%). Its survival could be attributed to lack of forestry activities between
      the 1950s and 1990s, slow succession preventing canopy closure and undergrowth
      expansion, and probably also to the distribution of habitat patches on
      conspicuous hill-tops. In order to increase chances of the population for long
      term survival, we propose to stop clear-cuts of old beech forests, increase semi
      open beech woodlands in areas currently covered by conifer plantations and active
      habitat management at inhabited sites and their wider environs.

PMID- 21738641
TI  - Evidence for human fronto-central gamma activity during long-term memory encoding
      of word sequences.
AB  - Although human gamma activity (30-80 Hz) associated with visual processing is
      often reported, it is not clear to what extend gamma activity can be reliably
      detected non-invasively from frontal areas during complex cognitive tasks such as
      long term memory (LTM) formation. We conducted a memory experiment composed of 35
      blocks each having three parts: LTM encoding, working memory (WM) maintenance and
      LTM retrieval. In the LTM encoding and WM maintenance parts, participants had to
      respectively encode or maintain the order of three sequentially presented words.
      During LTM retrieval subjects had to reproduce these sequences. Using
      magnetoencephalography (MEG) we identified significant differences in the gamma
      and beta activity. Robust gamma activity (55-65 Hz) in left BA6 (supplementary
      motor area (SMA)/pre-SMA) was stronger during LTM rehearsal than during WM
      maintenance. The gamma activity was sustained throughout the 3.4 s rehearsal
      period during which a fixation cross was presented. Importantly, the difference
      in gamma band activity correlated with memory performance over subjects. Further
      we observed a weak gamma power difference in left BA6 during the first half of
      the LTM rehearsal interval larger for successfully than unsuccessfully reproduced
      word triplets. In the beta band, we found a power decrease in left anterior
      regions during LTM rehearsal compared to WM maintenance. Also this suppression of
      beta power correlated with memory performance over subjects. Our findings show
      that an extended network of brain areas, characterized by oscillatory activity in
      different frequency bands, supports the encoding of word sequences in LTM. Gamma
      band activity in BA6 possibly reflects memory processes associated with language
      and timing, and suppression of beta activity at left frontal sensors is likely to
      reflect the release of inhibition directly associated with the engagement of
      language functions.

PMID- 21738642
TI  - Bocavirus episome in infected human tissue contains non-identical termini.
AB  - Human bocaviruses (HBoV) are highly prevalent human infections whose pathogenic
      potential remains unknown. Recent identification of the first non-human primate
      bocavirus [1] in captive gorillas raised the possibility of the persistent nature
      of bocavirus infection. To characterize bocavirus infection in humans, we tested
      intestinal biopsies from 22 children with gastrointestinal disease for the
      presence of HBoV DNA. Four HBoV-positive tissue samples were analyzed to
      determine whether viral DNA was present in the linear genomic, the episomal
      closed circular or the host genome-integrated form. Whereas one tissue sample
      positive for HBoV3 contained the episomal form (HBoV3-E1), none had the genome
      integrated form. The complete genome sequence of HBoV3-E1 contains 5319
      nucleotides of which 513 represent the non-coding terminal sequence. The
      secondary structure of HBoV3-E1 termini suggests several conserved and variable
      features among human and animal bocaviruses. Our observation that HBoV genome
      exists as head-to-tail monomer in infected tissue either reflects the likely
      evolution of alternative replication mechanism in primate bocaviruses or a
      mechanism of viral persistence in their host. Moreover, we identified the HBoV
      genomic terminal sequences that will be helpful in developing reverse genetic
      systems for these widely prevalent parvoviruses. SIGNIFICANCE: HBoV have been
      found in healthy human controls as well as individuals with respiratory or
      gastrointestinal disease. Our findings suggest that HBoV DNA can exist as
      episomes in infected human tissues and therefore can likely establish persistent
      infection in the host. Previous efforts to grow HBoV in cell culture and to
      develop reverse genetic systems have been unsuccessful. Complete genomic sequence
      of the HBoV3 episome and its genomic termini will improve our understanding of
      HBoV replication mechanism and its pathogenesis.

PMID- 21738643
TI  - Preparation of pre-confluent retinal cells increases graft viability in vitro and
      in vivo: a mouse model.
AB  - PURPOSE: Graft failure remains an obstacle to experimental subretinal cell
      transplantation. A key step is preparing a viable graft, as high levels of
      necrosis and apoptosis increase the risk of graft failure. Retinal grafts are
      commonly harvested from cell cultures. We termed the graft preparation procedure
      "transplant conditions" (TC). We hypothesized that culture conditions influenced
      graft viability, and investigated whether viability decreased following TC using
      a mouse retinal pigment epithelial (RPE) cell line, DH01. METHODS: Cell viability
      was assessed by trypan blue exclusion. Levels of apoptosis and necrosis in vitro
      were determined by flow cytometry for annexin V and propidium iodide and Western
      blot analysis for the pro- and cleaved forms of caspases 3 and 7. Graft viability
      in vivo was established by terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) and cleaved caspase 3 immunolabeling of subretinal allografts.
      RESULTS: Pre-confluent cultures had significantly less nonviable cells than post
      confluent cultures (6.6%+/-0.8% vs. 13.1%+/-0.9%, p<0.01). Cell viability in
      either group was not altered significantly following TC. Caspases 3 and 7 were
      not altered by levels of confluence or following TC. Pre-confluent cultures had
      low levels of apoptosis/necrosis (5.6%+/-1.1%) that did not increase following TC
      (4.8%+/-0.5%). However, culturing beyond confluence led to progressively
      increasing levels of apoptosis and necrosis (up to 16.5%+/-0.9%). Allografts
      prepared from post-confluent cultures had significantly more TUNEL-positive cells
      3 hours post-operatively than grafts of pre-confluent cells (12.7%+/-3.1% vs.
      4.5%+/-1.4%, p<0.001). Subretinal grafts of post-confluent cells also had
      significantly higher rates of cleaved caspase 3 than pre-confluent grafts
      (20.2%+/-4.3% vs. 7.8%+/-1.8%, p<0.001). CONCLUSION: Pre-confluent cells should
      be used to maximize graft cell viability.

PMID- 21738644
TI  - Neural stem cells achieve and maintain pluripotency without feeder cells.
AB  - BACKGROUND: Differentiated cells can be reprogrammed into pluripotency by
      transduction of four defined transcription factors. Induced pluripotent stem
      cells (iPS cells) are expected to be useful for regenerative medicine as well as
      basic research. Recently, the report showed that mouse embryonic fibroblasts
      (MEF) cells are not essential for reprogramming. However, in using fibroblasts as
      donor cells for reprogramming, individual fibroblasts that had failed to
      reprogram could function as feeder cells. METHODOLOGY/PRINCIPAL FINDING: Here, we
      show that adult mouse neural stem cells (NSCs), which are not functional feeder
      cells, can be reprogrammed into iPS cells using defined four factors (Oct4, Sox2,
      Klf4, and c-Myc) under feeder-free conditions. The iPS cells, generated from NSCs
      expressing the Oct4-GFP reporter gene, could proliferate for more than two months
      (passage 20). Generated and maintained without feeder cells, these iPS cells
      expressed pluripotency markers (Oct4 and Nanog), the promoter regions of Oct4 and
      Nanog were hypomethylated, could differentiated into to all three germ layers in
      vitro, and formed a germline chimera. These data indicate that NSCs can achieve
      and maintain pluripotency under feeder-free conditions. CONCLUSION/SIGNIFICANCE:
      This study suggested that factors secreted by feeder cells are not essential in
      the initial/early stages of reprogramming and for pluripotency maintenance. This
      technology might be useful for a human system, as a feeder-free reprogramming
      system may help generate iPS cells of a clinical grade for tissue or organ
      regeneration.

PMID- 21738645
TI  - Cancer risk associated with insulin glargine among adult type 2 diabetes patients
      -a nationwide cohort study.
AB  - BACKGROUND: Preclinical and observational studies raise the concern about the
      safety of insulin glargine in terms of cancer initiation and promotion. This
      study is designed to examine cancer incidence associated with use of insulin
      glargine vs. intermediate/long-acting human insulin (HI). METHODOLOGY: A
      retrospective cohort study using the Taiwan National Health Insurance claims
      database was conducted to identify adult patients with type 2 diabetes mellitus
      and without a history of cancer who initiated insulin glargine (n = 10,190) or
      intermediate/long-acting HI (n = 49,253) during 2004-2007. Exclusive users were
      followed from the date of insulin initiation to the earliest of cancer diagnosis,
      death, disenrollment, or December 31 2007. We estimated adjusted hazard ratios
      and 95% confidence intervals (CIs) with Cox proportional hazards models adjusting
      for baseline propensity score. FINDINGS: The incidence rate of all cancer per
      1,000 person-years was 13.8 for insulin glargine initiators (179 cases) and 16.0
      for intermediate/long-acting HI initiators (1,445 cases) during an average follow
      up of 2 years. No significant difference in overall cancer risk between insulin
      glargine initiators and HI initiators was found. For men, however, the adjusted
      hazard ratio of insulin glargine use as compared with intermediate/long-acting HI
      was 2.15 (95% CI 1.01-4.59) for pancreatic cancer, and 2.42 (95% CI 1.50-8.40)
      for prostate cancer. The increased risk was not observed among women.
      CONCLUSIONS: Insulin glargine use did not increase the risk of overall cancer
      incidence as compared with HI. The positive associations with pancreatic and
      prostate cancer need further evaluation and validation.

PMID- 21738646
TI  - Reanalysis of "Raptorex kriegsteini": a juvenile tyrannosaurid dinosaur from
      Mongolia.
AB  - The carnivorous Tyrannosauridae are among the most iconic dinosaurs: typified by
      large body size, tiny forelimbs, and massive robust skulls with laterally
      thickened teeth. The recently described small-bodied tyrannosaurid Raptorex
      kreigsteini is exceptional as its discovery proposes that many of the distinctive
      anatomical traits of derived tyrannosaurids were acquired in the Early
      Cretaceous, before the evolution of large body size. This inference depends on
      two core interpretations: that the holotype (LH PV18) derives from the Lower
      Cretaceous of China, and that despite its small size, it is a subadult or young
      adult. Here we show that the published data is equivocal regarding stratigraphic
      position and that ontogenetic reanalysis shows there is no reason to conclude
      that LH PV18 has reached this level of maturity. The probable juvenile status of
      LH PV18 makes its use as a holotype unreliable, since diagnostic features of
      Raptorex may be symptomatic of its immature status, rather than its actual
      phylogenetic position. These findings are consistent with the original sale
      description of LH PV18 as a juvenile Tarbosaurus from the Upper Cretaceous of
      Mongolia. Consequently, we suggest that there is currently no evidence to support
      the conclusion that tyrannosaurid skeletal design first evolved in the Early
      Cretaceous at small body size.

PMID- 21738647
TI  - Exceptional hyperthyroidism and a role for both major histocompatibility class I
      and class II genes in a murine model of Graves' disease.
AB  - Autoimmune hyperthyroidism, Graves' disease, can be induced by immunizing
      susceptible strains of mice with adenovirus encoding the human thyrotropin
      receptor (TSHR) or its A-subunit. Studies in two small families of recombinant
      inbred strains showed that susceptibility to developing TSHR antibodies (measured
      by TSH binding inhibition, TBI) was linked to the MHC region whereas genes on
      different chromosomes contributed to hyperthyroidism. We have now investigated
      TSHR antibody production and hyperthyroidism induced by TSHR A-subunit adenovirus
      immunization of a larger family of strains (26 of the AXB and BXA strains).
      Analysis of the combined AXB and BXA families provided unexpected insight into
      several aspects of Graves' disease. First, extreme thyroid hyperplasia and
      hyperthyroidism in one remarkable strain, BXA13, reflected an inability to
      generate non-functional TSHR antibodies measured by ELISA. Although neutral TSHR
      antibodies have been detected in Graves' sera, pathogenic, functional TSHR
      antibodies in Graves' patients are undetectable by ELISA. Therefore, this strain
      immunized with A-subunit-adenovirus that generates only functional TSHR
      antibodies may provide an improved model for studies of induced Graves' disease.
      Second, our combined analysis of linkage data from this and previous work
      strengthens the evidence that gene variants in the immunoglobulin heavy chain V
      region contribute to generating thyroid stimulating antibodies. Third, a broad
      region that encompasses the MHC region on mouse chromosome 17 is linked to the
      development of TSHR antibodies (measured by TBI). Most importantly, unlike other
      strains, TBI linkage in the AXB and BXA families to MHC class I and class II
      genes provides an explanation for the unresolved class I/class II difference in
      humans.

PMID- 21738648
TI  - Functional analysis of retinitis pigmentosa 2 (RP2) protein reveals variable
      pathogenic potential of disease-associated missense variants.
AB  - Genetic mutations are frequently associated with diverse phenotypic consequences,
      which limits the interpretation of the consequence of a variation in patients.
      Mutations in the retinitis pigmentosa 2 (RP2) gene are associated with X-linked
      RP, which is a phenotypically heterogenic form of retinal degeneration. The
      purpose of this study was to assess the functional consequence of disease
      associated mutations in the RP2 gene using an in vivo assay. Morpholino-mediated
      depletion of rp2 in zebrafish resulted in perturbations in photoreceptor
      development and microphthalmia (small eye). Ultrastructural and
      immunofluorescence analyses revealed defective photoreceptor outer segment
      development and lack of expression of photoreceptor-specific proteins. The
      retinopathy phenotype could be rescued by expressing the wild-type human RP2
      protein. Notably, the tested RP2 mutants exhibited variable degrees of rescue of
      rod versus cone photoreceptor development as well as microphthalmia. Our results
      suggest that RP2 plays a key role in photoreceptor development and maintenance in
      zebrafish and that the clinical heterogeneity associated with RP2 mutations may,
      in part, result from its potentially distinct functional relevance in rod versus
      cone photoreceptors.

PMID- 21738649
TI  - Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications.
AB  - Recent studies have shown aberrant expression of SOX11 in various types of
      aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to
      such deregulation, we performed a comprehensive SOX11 gene expression and
      epigenetic study in stem cells, normal hematopoietic cells and different lymphoid
      neoplasms. We observed that SOX11 expression is associated with unmethylated DNA
      and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic
      stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells,
      normal hematopoietic cells and other lymphoid neoplasms do not express SOX11.
      Such repression was associated with silencing histone marks H3K9me2 and H3K27me3.
      The SOX11 promoter of non-malignant cells was consistently unmethylated whereas
      lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation.
      SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor
      SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate
      that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms,
      it seems to be functionally inert, as SOX11 is already silenced in the
      hematopoietic system. In contrast, the pathogenic role of SOX11 is associated
      with its de novo expression in some aggressive lymphoid malignancies, which is
      mediated by a shift from inactivating to activating histone modifications.

PMID- 21738650
TI  - The cytosolic domain of Fis1 binds and reversibly clusters lipid vesicles.
AB  - Every lipid membrane fission event involves the association of two apposing
      bilayers, mediated by proteins that can promote membrane curvature, fusion and
      fission. We tested the hypothesis that Fis1, a tail-anchored protein involved in
      mitochondrial and peroxisomal fission, promotes changes in membrane structure. We
      found that the cytosolic domain of Fis1 alone binds lipid vesicles, which is
      enhanced upon protonation and increasing concentrations of anionic phospholipids.
      Fluorescence and circular dichroism data indicate that the cytosolic domain
      undergoes a membrane-induced conformational change that buries two tryptophan
      side chains upon membrane binding. Light scattering and electron microscopy data
      show that membrane binding promotes lipid vesicle clustering. Remarkably, this
      vesicle clustering is reversible and vesicles largely retain their original shape
      and size. This raises the possibility that the Fis1 cytosolic domain might act in
      membrane fission by promoting a reversible membrane association, a necessary step
      in membrane fission.

PMID- 21738651
TI  - Feeding behaviour, swimming activity and boldness explain variation in feed
      intake and growth of sole (Solea solea) reared in captivity.
AB  - The major economic constraint for culturing sole (Solea solea) is its slow and
      variable growth. The objective was to study the relationship between feed
      intake/efficiency, growth, and (non-) feeding behaviour of sole. Sixteen
      juveniles with an average (SD) growth of 2.7 (1.9) g/kg(0.8)/d were selected on
      their growth during a 4-week period in which they were housed communally with 84
      other fish. Selected fish were housed individually during a second 4-week period
      to measure individual feed intake, growth, and behaviour. Fish were hand-fed
      three times a day during the dark phase of the day until apparent satiation.
      During six different days, behaviour was recorded twice daily during 3 minutes by
      direct observations. Total swimming activity, frequency of burying and of escapes
      were recorded. At the beginning and end of the growth period, two sequential
      behavioural tests were performed: "Novel Environment" and "Light Avoidance". Fish
      housed individually still exhibited pronounced variation in feed intake (CV =
      23%), growth (CV = 25%) and behavior (CV = 100%). Differences in feed intake
      account for 79% of the observed individual differences in growth of sole. Fish
      with higher variation in feed intake between days and between meals within days
      had significantly a lower total feed intake (r = -0.65 and r = -0.77) and growth.
      Active fish showed significantly higher feed intake (r = 0.66) and growth (r =
      0.58). Boldness during both challenge tests was related to fast growth: (1) fish
      which reacted with a lower latency time to swim in a novel environment had
      significantly higher feed intake (r = -0.55) and growth (r = -0.66); (2) fish
      escaping during the light avoidance test tended to show higher feed intake
      (P<0.1) and had higher growth (P<0.05). In conclusion, feeding consistency,
      swimming activity in the tank, and boldness during behavioral tests are related
      to feed intake and growth of sole in captivity.

PMID- 21738652
TI  - An FPGA implementation to detect selective cationic antibacterial peptides.
AB  - Exhaustive prediction of physicochemical properties of peptide sequences is used
      in different areas of biological research. One example is the identification of
      selective cationic antibacterial peptides (SCAPs), which may be used in the
      treatment of different diseases. Due to the discrete nature of peptide sequences,
      the physicochemical properties calculation is considered a high-performance
      computing problem. A competitive solution for this class of problems is to embed
      algorithms into dedicated hardware. In the present work we present the
      adaptation, design and implementation of an algorithm for SCAPs prediction into a
      Field Programmable Gate Array (FPGA) platform. Four physicochemical properties
      codes useful in the identification of peptide sequences with potential selective
      antibacterial activity were implemented into an FPGA board. The speed-up gained
      in a single-copy implementation was up to 108 times compared with a single Intel
      processor cycle for cycle. The inherent scalability of our design allows for
      replication of this code into multiple FPGA cards and consequently improvements
      in speed are possible. Our results show the first embedded SCAPs prediction
      solution described and constitutes the grounds to efficiently perform the
      exhaustive analysis of the sequence-physicochemical properties relationship of
      peptides.

PMID- 21738653
TI  - Effect of commercially available egg cures on the survival of juvenile salmonids.
AB  - There is some concern that incidental consumption of eggs cured with commercially
      available cures for the purpose of sport fishing causes mortality in juvenile
      salmon. We evaluated this by feeding juvenile spring Chinook (Oncorhynchus
      tshawytscha) and steelhead (O. mykiss) with eggs cured with one of five
      commercially available cures. We observed significant levels of mortality in both
      pre-smolts and smolts. Depending on the experiment, 2, 3, or 4 of the cures were
      associated with mortality. Mortality tended to be higher in the smolts than in
      the parr, but there was no clear species effect. The majority of mortality
      occurred within the first 10 d of feeding. Removal of sodium sulfite from the
      cure significantly reduced the level of mortality. Soaking the eggs prior to
      feeding did not reduce mortality. We observed a clear relationship between the
      amount of cured egg consumed each day and the survival time. We conclude that
      consumption of eggs cured with sodium sulfite has the potential to cause
      mortality in juvenile steelhead and Chinook salmon in the wild.

PMID- 21738654
TI  - Rate-independent constructs for chemical computation.
AB  - This paper presents a collection of computational modules implemented with
      chemical reactions: an inverter, an incrementer, a decrementer, a copier, a
      comparator, a multiplier, an exponentiator, a raise-to-a-power operation, and a
      logarithm in base two. Unlike previous schemes for chemical computation, this
      method produces designs that are dependent only on coarse rate categories for the
      reactions ("fast" vs. "slow"). Given such categories, the computation is exact
      and independent of the specific reaction rates. The designs are validated through
      stochastic simulations of the chemical kinetics.

PMID- 21738655
TI  - Berberine inhibits human hepatoma cell invasion without cytotoxicity in healthy
      hepatocytes.
AB  - Conventional chemotherapy fails to cure metastatic hepatoma mainly due to its
      high hepatotoxicity. Many plant-derived agents have been accepted to effectively
      inhibit hepatoma cell invasion. However, the investigation that whether effectual
      plant-derived agents against invasive hepatoma cells exert unexpected
      cytotoxicity in healthy hepatocytes has been ignored. This study demonstrated
      that berberine exhibited significant cytotoxicity in HepG2 cells mainly through
      upregulation of reactive oxygen species (ROS) production but was ineffective in
      normal Chang liver cells. Berberine exerted anti-invasive effect on HepG2 cells
      through suppression of matrix metalloproteinase-9 (MMP-9) expression. Moreover,
      berberine could significantly inhibit the activity of PI3K-AKT and ERK pathways.
      Combination treatment of ERK pathway inhibitor PD98059 or AKT pathway inhibitor
      LY294002 and berberine could result in a synergistic reduction on MMP-9
      expression along with an inhibition of cell invasion. Enhancement of ROS
      production by berberine had no influence on its suppressive effects on the
      activity of PI3K-AKT and ERK pathways, as well as MMP-9 expression and HepG2 cell
      invasion. In conclusion, our results suggest that berberine may be a potential
      alternative against invasive hepatoma cells through PI3K-AKT and ERK pathways
      dependent downregulation of MMP-9 expression. This study also provides a
      previously neglected insight into the investigation of plant-derived agents-based
      therapy against tumor invasion with the consideration of damage to healthy cells.

PMID- 21738656
TI  - Expression of MAGE-C1/CT7 and MAGE-C2/CT10 predicts lymph node metastasis in
      melanoma patients.
AB  - MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer
      testis (CT) antigens. CT antigens are promising targets for immunotherapy in
      cancer because their expression is restricted to cancer and germ line cells and a
      proportion of cancer patients presents with immune responses against CT antigens,
      which clearly demonstrates their immunogenicity. This study investigates the
      expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma.
      Immunohistochemical staining of tissue microarrays that consisted of 59 primary
      malignant melanomas of the skin, 163 lymph node and distant melanoma metastases
      and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15
      out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE
      C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68
      (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of
      melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary
      melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001,
      resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was
      independent of tumor cell proliferation rate (Ki67 labeling index) in a
      multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE
      C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel
      lymph node metastasis.

PMID- 21738657
TI  - Impairment of auditory-motor timing and compensatory reorganization after ventral
      premotor cortex stimulation.
AB  - Integrating auditory and motor information often requires precise timing as in
      speech and music. In humans, the position of the ventral premotor cortex (PMv) in
      the dorsal auditory stream renders this area a node for auditory-motor
      integration. Yet, it remains unknown whether the PMv is critical for auditory
      motor timing and which activity increases help to preserve task performance
      following its disruption. 16 healthy volunteers participated in two sessions with
      fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a
      control region. Subjects synchronized left or right finger tapping to sub-second
      beat rates of auditory rhythms in the experimental task, and produced self-paced
      tapping during spectrally matched auditory stimuli in the control task. Left PMv
      rTMS impaired auditory-motor synchronization accuracy in the first sub-block
      following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and
      attention to task. Task-related activity increased in the homologue right PMv,
      but did not predict the behavioral effect of rTMS. In contrast, anterior midline
      cerebellum revealed most pronounced activity increase in less impaired subjects.
      The present findings suggest a critical role of the left PMv in feed-forward
      computations enabling accurate auditory-motor timing, which can be compensated by
      activity modulations in the cerebellum, but not in the homologue region
      contralateral to stimulation.

PMID- 21738658
TI  - Common functional correlates of head-strike behavior in the pachycephalosaur
      Stegoceras validum (Ornithischia, Dinosauria) and combative artiodactyls.
AB  - BACKGROUND: Pachycephalosaurs were bipedal herbivorous dinosaurs with bony domes
      on their heads, suggestive of head-butting as seen in bighorn sheep and musk
      oxen. Previous biomechanical studies indicate potential for pachycephalosaur head
      butting, but bone histology appears to contradict the behavior in young and old
      individuals. Comparing pachycephalosaurs with fighting artiodactyls tests for
      common correlates of head-butting in their cranial structure and mechanics.
      METHODS/PRINCIPAL FINDINGS: Computed tomographic (CT) scans and physical
      sectioning revealed internal cranial structure of ten artiodactyls and
      pachycephalosaurs Stegoceras validum and Prenocephale prenes. Finite element
      analyses (FEA), incorporating bone and keratin tissue types, determined cranial
      stress and strain from simulated head impacts. Recursive partition analysis
      quantified strengths of correlation between functional morphology and actual or
      hypothesized behavior. Strong head-strike correlates include a dome-like cephalic
      morphology, neurovascular canals exiting onto the cranium surface, large neck
      muscle attachments, and dense cortical bone above a sparse cancellous layer in
      line with the force of impact. The head-butting duiker Cephalophus leucogaster is
      the closest morphological analog to Stegoceras, with a smaller yet similarly
      rounded dome. Crania of the duiker, pachycephalosaurs, and bighorn sheep Ovis
      canadensis share stratification of thick cortical and cancellous layers.
      Stegoceras, Cephalophus, and musk ox crania experience lower stress and higher
      safety factors for a given impact force than giraffe, pronghorn, or the non
      combative llama. CONCLUSIONS/SIGNIFICANCE: Anatomy, biomechanics, and statistical
      correlation suggest that some pachycephalosaurs were as competent at head-to-head
      impacts as extant analogs displaying such combat. Large-scale comparisons and
      recursive partitioning can greatly refine inference of behavioral capability for
      fossil animals.

PMID- 21738659
TI  - The N-terminal amphipathic helix of the topological specificity factor MinE is
      associated with shaping membrane curvature.
AB  - Pole-to-pole oscillations of the Min proteins in Escherichia coli are required
      for the proper placement of the division septum. Direct interaction of MinE with
      the cell membrane is critical for the dynamic behavior of the Min system. In
      vitro, this MinE-membrane interaction led to membrane deformation; however, the
      underlying mechanism remained unclear. Here we report that MinE-induced membrane
      deformation involves the formation of an amphipathic helix of MinE(2-9), which,
      together with the adjacent basic residues, function as membrane anchors.
      Biochemical evidence suggested that the membrane association induces formation of
      the helix, with the helical face, consisting of A2, L3, and F6, inserted into the
      membrane. Insertion of this helix into the cell membrane can influence local
      membrane curvature and lead to drastic changes in membrane topology. Accordingly,
      MinE showed characteristic features of protein-induced membrane tubulation and
      lipid clustering in in vitro reconstituted systems. In conclusion, MinE shares
      common protein signatures with a group of membrane trafficking proteins in
      eukaryotic cells. These MinE signatures appear to affect membrane curvature.

PMID- 21738660
TI  - Geographical detector-based risk assessment of the under-five mortality in the
      2008 Wenchuan earthquake, China.
AB  - On 12 May, 2008, a devastating earthquake registering 8.0 on the Richter scale
      occurred in Sichuan Province, China, taking tens of thousands of lives and
      destroying the homes of millions of people. Many of the deceased were children,
      particular children less than five years old who were more vulnerable to such a
      huge disaster than the adult. In order to obtain information specifically
      relevant to further researches and future preventive measures, potential risk
      factors associated with earthquake-related child mortality need to be identified.
      We used four geographical detectors (risk detector, factor detector, ecological
      detector, and interaction detector) based on spatial variation analysis of some
      potential factors to assess their effects on the under-five mortality. It was
      found that three factors are responsible for child mortality: earthquake
      intensity, collapsed house, and slope. The study, despite some limitations, has
      important implications for both researchers and policy makers.

PMID- 21738661
TI  - Application of MLST and pilus gene sequence comparisons to investigate the
      population structures of Actinomyces naeslundii and Actinomyces oris.
AB  - Actinomyces naeslundii and Actinomyces oris are members of the oral biofilm.
      Their identification using 16S rRNA sequencing is problematic and better achieved
      by comparison of metG partial sequences. A. oris is more abundant and more
      frequently isolated than A. naeslundii. We used a multi-locus sequence typing
      approach to investigate the genotypic diversity of these species and assigned A.
      naeslundii (n = 37) and A. oris (n = 68) isolates to 32 and 68 sequence types
      (ST), respectively. Neighbor-joining and ClonalFrame dendrograms derived from the
      concatenated partial sequences of 7 house-keeping genes identified at least 4
      significant subclusters within A. oris and 3 within A. naeslundii. The strain
      collection we had investigated was an under-representation of the total
      population since at least 3 STs composed of single strains may represent discrete
      clusters of strains not well represented in the collection. The integrity of
      these sub-clusters was supported by the sequence analysis of fimP and fimA, genes
      coding for the type 1 and 2 fimbriae, respectively. An A. naeslundii subcluster
      was identified with both fimA and fimP genes and these strains were able to bind
      to MUC7 and statherin while all other A. naeslundii strains possessed only fimA
      and did not bind to statherin. An A. oris subcluster harboured a fimA gene
      similar to that of Actinomyces odontolyticus but no detectable fimP failed to
      bind significantly to either MUC7 or statherin. These data are evidence of
      extensive genotypic and phenotypic diversity within the species A. oris and A.
      naeslundii but the status of the subclusters identified here will require genome
      comparisons before their phylogenic position can be unequivocally established.

PMID- 21738662
TI  - Discordant gene expression signatures and related phenotypic differences in lamin
      A- and A/C-related Hutchinson-Gilford progeria syndrome (HGPS).
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder displaying
      features reminiscent of premature senescence caused by germline mutations in the
      LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By
      studying a family with homozygous LMNA mutation (K542N), we showed that HGPS can
      also be caused by mutations affecting both isoforms, lamin A and C. Here, we
      aimed to elucidate the molecular mechanisms underlying the pathogenesis in both,
      lamin A- (sporadic) and lamin A and C-related (hereditary) HGPS. For this, we
      performed detailed molecular studies on primary fibroblasts of hetero- and
      homozygous LMNA K542N mutation carriers, accompanied with clinical examinations
      related to the molecular findings. By assessing global gene expression we found
      substantial overlap in altered transcription profiles (13.7%; 90/657) in sporadic
      and hereditary HGPS, with 83.3% (75/90) concordant and 16.7% (15/90) discordant
      transcriptional changes. Among the concordant ones we observed down-regulation of
      TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat
      and dermal appendages, and loss of expression in dermal fibroblasts and
      periadnexial cells from a LMNA(K542N/K542N) patient further confirming its
      pivotal role in skin development. Among the discordant transcriptional profiles
      we identified two key mediators of vascular calcification and bone metabolism,
      ENPP1 and OPG, which offer a molecular explanation for the major phenotypic
      differences in vascular and bone disease in sporadic and hereditary HGPS.
      Finally, this study correlates reduced TWIST2 and OPG expression with increased
      osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis
      in hereditary HGPS.

PMID- 21738663
TI  - Acoustic communication at the water's edge: evolutionary insights from a
      mudskipper.
AB  - Coupled behavioural observations and acoustical recordings of aggressive dyadic
      contests showed that the mudskipper Periophthalmodon septemradiatus communicates
      acoustically while out of water. An analysis of intraspecific variability showed
      that specific acoustic components may act as tags for individual recognition,
      further supporting the sounds' communicative value. A correlative analysis
      amongst acoustical properties and video-acoustical recordings in slow-motion
      supported first hypotheses on the emission mechanism. Acoustic transmission
      through the wet exposed substrate was also discussed. These observations were
      used to support an "exaptation hypothesis", i.e. the maintenance of key
      adaptations during the first stages of water-to-land vertebrate eco-evolutionary
      transitions (based on eco-evolutionary and palaeontological considerations),
      through a comparative bioacoustic analysis of aquatic and semiterrestrial gobiid
      taxa. In fact, a remarkable similarity was found between mudskipper vocalisations
      and those emitted by gobioids and other soniferous benthonic fishes.

PMID- 21738664
TI  - Diversity of murine norovirus strains isolated from asymptomatic mice of
      different genetic backgrounds within a single U.S. research institute.
AB  - Antibody prevalence studies in laboratory mice indicate that murine norovirus
      (MNV) infections are common, but the natural history of these viruses has not
      been fully established. This study examined the extent of genetic diversity of
      murine noroviruses isolated from healthy laboratory mice housed in multiple
      animal facilities within a single, large research institute- the National
      Institute of Allergy and Infectious Diseases of the National Institutes of Health
      (NIAID-NIH) in Bethesda, Maryland, U.S. Ten distinct murine norovirus strains
      were isolated from various tissues and feces of asymptomatic wild type sentinel
      mice as well as asymptomatic immunodeficient (RAG 2(-/-)) mice. The NIH MNV
      isolates showed little cytopathic effect in permissive RAW264.7 cells in early
      passages, but all isolates examined could be adapted to efficient growth in cell
      culture by serial passage. The viruses, although closely related in genome
      sequence, were distinguishable from each other according to facility location,
      likely due to the introduction of new viruses into each facility from separate
      sources or vendors at different times. Our study indicates that the murine
      noroviruses are widespread in these animal facilities, despite rigorous
      guidelines for animal care and maintenance.

PMID- 21738665
TI  - Single-step production of a recyclable nanobiocatalyst for organophosphate
      pesticides biodegradation using functionalized bacterial magnetosomes.
AB  - Enzymes are versatile catalysts in laboratories and on an industrial scale;
      improving their immobilization would be beneficial to broadening their
      applicability and ensuring their (re)use. Lipid-coated nano-magnets produced by
      magnetotactic bacteria are suitable for a universally applicable single-step
      method of enzyme immobilization. By genetically functionalizing the membrane
      surrounding these magnetite particles with a phosphohydrolase, we engineered an
      easy-to-purify, robust and recyclable biocatalyst to degrade ethyl-paraoxon, a
      commonly used pesticide. For this, we genetically fused the opd gene from
      Flavobacterium sp. ATCC 27551 encoding a paraoxonase to mamC, an abundant protein
      of the magnetosome membrane in Magnetospirillum magneticum AMB-1. The MamC
      protein acts as an anchor for the paraoxonase to the magnetosome surface, thus
      producing magnetic nanoparticles displaying phosphohydrolase activity.
      Magnetosomes functionalized with Opd were easily recovered from genetically
      modified AMB-1 cells: after cellular disruption with a French press, the magnetic
      nanoparticles are purified using a commercially available magnetic separation
      system. The catalytic properties of the immobilized Opd were measured on ethyl
      paraoxon hydrolysis: they are comparable with the purified enzyme, with K(m) (and
      k(cat)) values of 58 uM (and 178 s(-1)) and 43 uM (and 314 s(-1)) for the
      immobilized and purified enzyme respectively. The Opd, a metalloenzyme requiring
      a zinc cofactor, is thus properly matured in AMB-1. The recycling of the
      functionalized magnetosomes was investigated and their catalytic activity proved
      to be stable over repeated use for pesticide degradation. In this study, we
      demonstrate the easy production of functionalized magnetic nanoparticles with
      suitably genetically modified magnetotactic bacteria that are efficient as a
      reusable nanobiocatalyst for pesticides bioremediation in contaminated effluents.

PMID- 21738666
TI  - The Balloon Analog Insurance Task (BAIT): a behavioral measure of protective risk
      management.
AB  - Prior methods used to assess individual differences related to risk have not
      focused on an important component of risk management: how willing individuals are
      to pay for or take actions to insure what they already have. It is not clear
      whether this type of protective risk management taps into the same individual
      differences as does risk taking propensity measured by existing risk taking
      tasks. We developed a novel task to assess protective risk management, the
      Balloon Analog Insurance Task (BAIT), which is modeled after the Balloon Analog
      Risk Task (BART). In the BAIT, individuals are forced to decide how much money
      they are willing to pay in order to insure a specific fraction of their prior
      winnings given changing but imprecise levels of risk of monetary loss.
      Participants completed the BART and BAIT for real monetary rewards, and completed
      six self report questionnaires. The amount of insurance purchased on the BAIT was
      positively correlated with scores on the Intolerance of Uncertainty Scale and on
      the Checking scale of the revised Obsessive Compulsive Inventory. Conversely, the
      amount of insurance purchased was negatively correlated with scores on the Domain
      Specific Risk Taking Questionnaire, and on the Psychopathic Personality Inventory
      (PPI). Furthermore, relationships between insurance purchased and these scales
      remained significant after controlling for the BART in linear regression
      analyses, and the BART was only a significant predictor for measures on one scale
      -the PPI. Our results reveal that behavior on the BAIT taps into a number of
      individual differences that are not related to behavior on another measure of
      risk taking. We propose that the BAIT may provide a useful complement to the BART
      in the assessment of risk management style.

PMID- 21738667
TI  - IL-6-mediated activation of Stat3alpha prevents trauma/hemorrhagic shock-induced
      liver inflammation.
AB  - Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity
      and mortality in the United States for individuals under the age of 44 years.
      Initial survivors are susceptible to developing multiple organ failure (MOF),
      which is thought to be caused, at least in part, by excessive or maladaptive
      activation of inflammatory pathways. We previously demonstrated in rodents that
      T/HS results in liver injury that can be prevented by IL-6 administration at the
      start of resuscitation; however, the contribution of the severity of HS to the
      extent of liver injury, whether or not resuscitation is required, and the
      mechanism(s) for the IL-6 protective effect have not been reported. In the
      experiments described here, we demonstrated that the extent of liver inflammation
      induced by T/HS depends on the duration of hypotension and requires
      resuscitation. We established that IL-6 administration at the start of
      resuscitation is capable of completely reversing liver inflammation and is
      associated with increased Stat3 activation. Global assessment of the livers
      showed that the main effect of IL-6 was to normalize the T/HS-induced
      inflammation transcriptome. Pharmacological inhibition of Stat3 activity within
      the liver blocked the ability of IL-6 to prevent liver inflammation and to
      normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of
      a Stat3beta, a naturally occurring, dominant-negative isoform of the Stat3,
      attenuated T/HS-induced liver inflammation, confirming a role for Stat3,
      especially Stat3alpha, in preventing T/HS-mediated liver inflammation. Thus, T/HS
      induced liver inflammation depends on the duration of hypotension and requires
      resuscitation; IL-6 administration at the start of resuscitation reverses T/HS
      induced liver inflammation, through activation of Stat3alpha, which normalized
      the T/HS-induced liver inflammation transcriptome.

PMID- 21738668
TI  - Randomized trial of time-limited interruptions of protease inhibitor-based
      antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection.
AB  - BACKGROUND: The clinical outcomes of short interruptions of PI-based ART regimens
      remains undefined. METHODS: A 2-arm non-inferiority trial was conducted on 53 HIV
      1 infected South African participants with viral load <50 copies/ml and CD4 T
      cell count >450 cells/ul on stavudine (or zidovudine), lamivudine and
      lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week
      ART interruptions or b) continuous ART (cART). Primary analysis was based on the
      proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug
      resistance, and CD4 count rise over time were analyzed as secondary endpoints.
      RESULTS: The proportions of CD4 counts >350 cells/ul were 82.12% for the
      intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above
      the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2
      sided CI: -0.16, 23.1). No clinically significant differences in opportunistic
      infections, adverse events, adherence or viral resistance were noted; after
      randomization, long-term CD4 rise was observed only in the cART arm. CONCLUSION:
      We are unable to conclude that short PI-based ART interruptions are non-inferior
      to cART in retention of immune reconstitution; however, short interruptions did
      not lead to a greater rate of resistance mutations or adverse events than cART
      suggesting that this regimen may be more forgiving than NNRTIs if interruptions
      in therapy occur. TRIAL REGISTRATION: ClinicalTrials.gov NCT00100646.

PMID- 21738669
TI  - A frameshift mutation in golden retriever dogs with progressive retinal atrophy
      endorses SLC4A3 as a candidate gene for human retinal degenerations.
AB  - Progressive retinal atrophy (PRA) in dogs, the canine equivalent of retinitis
      pigmentosa (RP) in humans, is characterised by vision loss due to degeneration of
      the photoreceptor cells in the retina, eventually leading to complete blindness.
      It affects more than 100 dog breeds, and is caused by numerous mutations. RP
      affects 1 in 4000 people in the Western world and 70% of causal mutations remain
      unknown. Canine diseases are natural models for the study of human diseases and
      are becoming increasingly useful for the development of therapies in humans. One
      variant, prcd-PRA, only accounts for a small proportion of PRA cases in the
      Golden Retriever (GR) breed. Using genome-wide association with 27 cases and 19
      controls we identified a novel PRA locus on CFA37 (p(raw) = 1.94*10(-10),
      p(genome) = 1.0*10(-5)), where a 644 kb region was homozygous within cases. A
      frameshift mutation was identified in a solute carrier anion exchanger gene
      (SLC4A3) located within this region. This variant was present in 56% of PRA cases
      and 87% of obligate carriers, and displayed a recessive mode of inheritance with
      full penetrance within those lineages in which it segregated. Allele frequencies
      are approximately 4% in the UK, 6% in Sweden and 2% in France, but the variant
      has not been found in GRs from the US. A large proportion of cases (approximately
      44%) remain unexplained, indicating that PRA in this breed is genetically
      heterogeneous and caused by at least three mutations. SLC4A3 is important for
      retinal function and has not previously been associated with spontaneously
      occurring retinal degenerations in any other species, including humans.

PMID- 21738670
TI  - Display of Bombyx mori alcohol dehydrogenases on the Bacillus subtilis spore
      surface to enhance enzymatic activity under adverse conditions.
AB  - Alcohol dehydrogenases (ADHs) are oxidoreductases catalyzing the reversible
      oxidation of alcohols to corresponding aldehydes or ketones accompanied by
      nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide
      phosphate (NADP) as coenzyme. ADHs attract major scientific and industrial
      interest for the evolutionary perspectives, afforded by their wide occurrence in
      nature, and for their use in industrial synthesis. However, the low activity of
      ADHs under extremes of pH and temperature often limits their application. To
      obtain ADH with high activity, in this study, we used Bombyx mori alcohol
      dehydrogenases (BmADH) as foreign gene and constructed a recombinant integrative
      plasmid pJS700-BmADH. This pJS700-BmADH was transformed into Bacillus subtilis by
      double cross-over and produced an amylase inactivated mutant. The fusion protein
      containing BmADH was expressed on the spore surface and recognized by BmADH
      specific antibody. We also assayed the alcohol dehydrogenase activity of the
      fusion protein together with the native BmADH at different pH and temperature
      levels, which indicated the recombinant enzyme exhibits activity over wider
      ranges of temperature and pH than its native form, perhaps due to the resistance
      properties of B. subtilis spores against adverse conditions.

PMID- 21738671
TI  - Identification of critical amino acids in the IgE epitopes of Ric c 1 and Ric c 3
      and the application of glutamic acid as an IgE blocker.
AB  - BACKGROUND: The allergenicity of Ricinus communis L. (castor bean, Euphorbiaceae)
      is associated with components of its seeds and pollen. Castor bean allergy has
      been described not only in laboratory workers, but also in personnel working in
      oil processing mills, fertilizer retail, the upholstery industry and other
      industrial fields. In the present study, we describe the critical amino acids in
      the IgE-binding epitopes in Ric c 1 and Ric c 3, two major allergens of R.
      communis. In addition, we also investigate the cross-reactivity between castor
      bean and some air and food allergen extracts commonly used in allergy diagnosis.
      METHODOLOGY/PRINCIPAL FINDINGS: The IgE reactivity of human sera from atopic
      patients was screened by immune-dot blot against castor bean allergens.
      Allergenic activity was evaluated in vitro using a rat mast cell activation assay
      and by ELISA. Cross-reactivity was observed between castor bean allergens and
      extracts from shrimp, fish, gluten, wheat, soybean, peanut, corn, house dust,
      tobacco and airborne fungal allergens. We observed that treatment of rat and
      human sera (from atopic patients) with glutamic acid reduced the IgE-epitope
      interaction. CONCLUSIONS/SIGNIFICANCE: The identification of glutamic acid
      residues with critical roles in IgE-binding to Ric c 3 and Ric c 1 support the
      potential use of free amino acids in allergy treatment.

PMID- 21738672
TI  - Activation of PKR causes amyloid beta-peptide accumulation via de-repression of
      BACE1 expression.
AB  - BACE1 is a key enzyme involved in the production of amyloid beta-peptide (Abeta)
      in Alzheimer's disease (AD) brains. Normally, its expression is constitutively
      inhibited due to the presence of the 5'untranslated region (5'UTR) in the BACE1
      promoter. BACE1 expression is activated by phosphorylation of the eukaryotic
      initiation factor (eIF)2-alpha, which reverses the inhibitory effect exerted by
      BACE1 5'UTR. There are four kinases associated with different types of stress
      that could phosphorylate eIF2-alpha. Here we focus on the double-stranded (ds)
      RNA-activated protein kinase (PKR). PKR is activated during viral infection,
      including that of herpes simplex virus type 1 (HSV1), a virus suggested to be
      implicated in the development of AD, acting when present in brains of carriers of
      the type 4 allele of the apolipoprotein E gene. HSV1 is a dsDNA virus but it has
      genes on both strands of the genome, and from these genes complementary RNA
      molecules are transcribed. These could activate BACE1 expression by the PKR
      pathway. Here we demonstrate in HSV1-infected neuroblastoma cells, and in
      peripheral nervous tissue from HSV1-infected mice, that HSV1 activates PKR.
      Cloning BACE1 5'UTR upstream of a luciferase (luc) gene confirmed its inhibitory
      effect, which can be prevented by salubrinal, an inhibitor of the eIF2-alpha
      phosphatase PP1c. Treatment with the dsRNA analog poly (I?C) mimicked the
      stimulatory effect exerted by salubrinal over BACE1 translation in the 5'UTR-luc
      construct and increased Abeta production in HEK-APPsw cells. Summarizing, our
      data suggest that PKR activated in brain by HSV1 could play an important role in
      the development of AD.

PMID- 21738674
TI  - Self-organization leads to supraoptimal performance in public transportation
      systems.
AB  - The performance of public transportation systems affects a large part of the
      population. Current theory assumes that passengers are served optimally when
      vehicles arrive at stations with regular intervals. In this paper, it is shown
      that self-organization can improve the performance of public transportation
      systems beyond the theoretical optimum by responding adaptively to local
      conditions. This is possible because of a "slower-is-faster" effect, where
      passengers wait more time at stations but total travel times are reduced. The
      proposed self-organizing method uses "antipheromones" to regulate headways, which
      are inspired by the stigmergy (communication via environment) of some ant
      colonies.

PMID- 21738673
TI  - M-CSF potently augments RANKL-induced resorption activation in mature human
      osteoclasts.
AB  - Macrophage-CSF (M-CSF) is critical for osteoclast (OC) differentiation and is
      reported to enhance mature OC survival and motility. However, its role in the
      regulation of bone resorption, the main function of OCs, has not been well
      characterised. To address this we analysed short-term cultures of fully
      differentiated OCs derived from human colony forming unit-granulocyte macrophages
      (CFU-GM). When cultured on dentine, OC survival was enhanced by M-CSF but more
      effectively by receptor activator of NFkappaB ligand (RANKL). Resorption was
      entirely dependent on the presence of RANKL. Co-treatment with M-CSF augmented
      RANKL-induced resorption in a concentration-dependent manner with a (200-300%)
      stimulation at 25 ng/mL, an effect observed within 4-6 h. M-CSF co-treatment also
      increased number of resorption pits and F-actin sealing zones, but not the number
      of OCs or pit size, indicating stimulation of the proportion of OCs activated. M
      CSF facilitated RANKL-induced activation of c-fos and extracellular signal
      regulated kinase (ERK) 1/2 phosphorylation, but not NFkappaB nor nuclear factor
      of activated T-cells, cytoplasmic-1 (NFATc1). The mitogen-activated protein
      kinase kinase (MEK) 1 inhibitor PD98059 partially blocked augmentation of
      resorption by M-CSF. Our results reveal a previously unidentified role of M-CSF
      as a potent stimulator of mature OC resorbing activity, possibly mediated via ERK
      upstream of c-fos.

PMID- 21738675
TI  - Towards a rigorous network of protein-protein interactions of the model sulfate
      reducer Desulfovibrio vulgaris Hildenborough.
AB  - Protein-protein interactions offer an insight into cellular processes beyond what
      may be obtained by the quantitative functional genomics tools of proteomics and
      transcriptomics. The aforementioned tools have been extensively applied to study
      Escherichia coli and other aerobes and more recently to study the stress response
      behavior of Desulfovibrio vulgaris Hildenborough, a model obligate anaerobe and
      sulfate reducer and the subject of this study. Here we carried out affinity
      purification followed by mass spectrometry to reconstruct an interaction network
      among 12 chromosomally encoded bait and 90 prey proteins based on 134 bait-prey
      interactions identified to be of high confidence. Protein-protein interaction
      data are often plagued by the lack of adequate controls and replication analyses
      necessary to assess confidence in the results, including identification of
      potential false positives. We addressed these issues through the use of
      biological replication, exponentially modified protein abundance indices, results
      from an experimental negative control, and a statistical test to assign
      confidence to each putative interacting pair applicable to small interaction data
      studies. We discuss the biological significance of metabolic features of D.
      vulgaris revealed by these protein-protein interaction data and the observed
      protein modifications. These include the distinct role of the putative carbon
      monoxide-induced hydrogenase, unique electron transfer routes associated with
      different oxidoreductases, and the possible role of methylation in regulating
      sulfate reduction.

PMID- 21738676
TI  - The geographic synchrony of seasonal influenza: a waves across Canada and the
      United States.
AB  - BACKGROUND: As observed during the 2009 pandemic, a novel influenza virus can
      spread globally before the epidemic peaks locally. As consistencies in the
      relative timing and direction of spread could form the basis for an early alert
      system, the objectives of this study were to use the case-based reporting system
      for laboratory confirmed influenza from the Canadian FluWatch surveillance
      program to identify the geographic scale at which spatial synchrony exists and
      then to describe the geographic patterns of influenza A virus across Canada and
      in relationship to activity in the United States (US). METHODOLOGY/PRINCIPAL
      FINDINGS: Weekly laboratory confirmations for influenza A were obtained from the
      Canadian FluWatch and the US FluView surveillance programs from 1997/98 to
      2006/07. For the six seasons where at least 80% of the specimens were
      antigenically similar, we identified the epidemic midpoint of the
      local/regional/provincial epidemics and analyzed trends in the direction of
      spread. In three out of the six seasons, the epidemic appeared first in Canada.
      Regional epidemics were more closely synchronized across the US (3-5 weeks)
      compared to Canada (5-13 weeks), with a slight gradient in timing from the
      southwest regions in the US to northeast regions of Canada and the US. Cities, as
      well as rural areas within provinces, usually peaked within a couple of weeks of
      each other. The anticipated delay in peak activity between large cities and rural
      areas was not observed. In some mixed influenza A seasons, lack of
      synchronization sub-provincially was evident. CONCLUSIONS/SIGNIFICANCE: As mixing
      between regions appears to be too weak to force a consistency in the direction
      and timing of spread, local laboratory-based surveillance is needed to accurately
      assess the level of influenza activity in the community. In comparison, mixing
      between urban communities and adjacent rural areas, and between some communities,
      may be sufficient to force synchronization.

PMID- 21738677
TI  - Integrated bio-entity network: a system for biological knowledge discovery.
AB  - A significant part of our biological knowledge is centered on relationships
      between biological entities (bio-entities) such as proteins, genes, small
      molecules, pathways, gene ontology (GO) terms and diseases. Accumulated at an
      increasing speed, the information on bio-entity relationships is archived in
      different forms at scattered places. Most of such information is buried in
      scientific literature as unstructured text. Organizing heterogeneous information
      in a structured form not only facilitates study of biological systems using
      integrative approaches, but also allows discovery of new knowledge in an
      automatic and systematic way. In this study, we performed a large scale
      integration of bio-entity relationship information from both databases containing
      manually annotated, structured information and automatic information extraction
      of unstructured text in scientific literature. The relationship information we
      integrated in this study includes protein-protein interactions, protein/gene
      regulations, protein-small molecule interactions, protein-GO relationships,
      protein-pathway relationships, and pathway-disease relationships. The
      relationship information is organized in a graph data structure, named integrated
      bio-entity network (IBN), where the vertices are the bio-entities and edges
      represent their relationships. Under this framework, graph theoretic algorithms
      can be designed to perform various knowledge discovery tasks. We designed breadth
      first search with pruning (BFSP) and most probable path (MPP) algorithms to
      automatically generate hypotheses--the indirect relationships with high
      probabilities in the network. We show that IBN can be used to generate plausible
      hypotheses, which not only help to better understand the complex interactions in
      biological systems, but also provide guidance for experimental designs.

PMID- 21738678
TI  - Genome-wide gene expression profiling of fertilization competent mycelium in
      opposite mating types in the heterothallic fungus Podospora anserina.
AB  - BACKGROUND: Mating-type loci in yeasts and ascomycotan filamentous fungi
      (Pezizomycotina) encode master transcriptional factors that play a critical role
      in sexual development. Genome-wide analyses of mating-type-specification circuits
      and mating-type target genes are available in Saccharomyces cerevisiae and
      Schizosaccharomyces pombe; however, no such analyses have been performed in
      heterothallic (self-incompatible) Pezizomycotina. The heterothallic fungus
      Podospora anserina serves as a model for understanding the basic features of
      mating-type control. Its mat+ and mat- mating types are determined by dissimilar
      allelic sequences. The mat- sequence contains three genes, designated FMR1, SMR1
      and SMR2, while the mat+ sequence contains one gene, FPR1. FMR1 and FPR1 are the
      major regulators of fertilization, and this study presents a genome-wide view of
      their target genes and analyzes their target gene regulation.
      METHODOLOGY/PRINCIPAL FINDINGS: The transcriptomic profiles of the mat+ and mat-
      strains revealed 157 differentially transcribed genes, and transcriptomic
      analysis of fmr1(-) and fpr1(-) mutant strains was used to determine the
      regulatory actions exerted by FMR1 and FPR1 on these differentially transcribed
      genes. All possible combinations of transcription repression and/or activation by
      FMR1 and/or FPR1 were observed. Furthermore, 10 additional mating-type target
      genes were identified that were up- or down-regulated to the same level in mat+
      and mat- strains. Of the 167 genes identified, 32 genes were selected for
      deletion, which resulted in the identification of two genes essential for the
      sexual cycle. Interspecies comparisons of mating-type target genes revealed
      significant numbers of orthologous pairs, although transcriptional profiles were
      not conserved between species. CONCLUSIONS/SIGNIFICANCE: This study represents
      the first comprehensive genome-wide analysis of mating-type direct and indirect
      target genes in a heterothallic filamentous fungus. Mating-type transcription
      factors have many more target genes than are found in yeasts and exert a much
      greater diversity of regulatory actions on target genes, most of which are not
      directly related to mating.

PMID- 21738679
TI  - Detection of Campylobacter concisus and other Campylobacter species in colonic
      biopsies from adults with ulcerative colitis.
AB  - INTRODUCTION: The critical role of bacteria in the pathogenesis of ulcerative
      colitis (UC) is well recognized, but an individual causative microorganism has
      not been singled out so far. Campylobacter concisus and other non-jejuni species
      of Campylobacter have been implicated as putative aetiological agents in
      inflammatory bowel disease in children, but such studies have not been addressed
      in adults. This study investigated the prevalence of Campylobacter species in
      colonic biopsy samples from adults with UC and healthy controls. METHODS: Adult
      patients who were undergoing diagnostic colonoscopy were recruited for the study,
      which included 69 patients with histologically proven UC and 65 healthy controls.
      DNA was extracted from the biopsy samples and subjected to Campylobacter genus
      specific and Campylobacter concisus specific polymerase chain reaction and
      sequencing. RESULTS: Detection of all Campylobacter DNA utilising genus specific
      primers was significantly higher in cases of UC, with a prevalence of 73.9%
      (51/69) compared to 23.1% (15/65) in controls (p = 0.0001). Nested PCR for C.
      concisus DNA was positive in 33.3% (23/69) of biopsy samples from subjects with
      UC, which was significantly higher than the prevalence rate of 10.8% (7/65) from
      controls (p = 0.0019). Sequencing of the remaining Campylobacter positive samples
      revealed that Campylobacter ureolyticus was positive in 21.7% (15/69) of samples
      from UC subjects as opposed to 3.1% (2/65) in controls (p = 0.0013). Mixed
      Campylobacter species were more common in UC patients, 20.3% (14/69) as compared
      to controls 4.6% (3/65) (p = 0.0084). CONCLUSION: The higher prevalence of
      Campylobacter genus and more specifically C. concisus and C. ureolyticus in
      biopsy samples from adults with UC suggests these genera of bacteria may be
      involved in the chronic inflammation that is characteristically seen in UC. To
      the best of our knowledge this is the first report of this association of C.
      concisus and C. ureolyticus with UC in adults.

PMID- 21738680
TI  - Virus-receptor mediated transduction of dendritic cells by lentiviruses enveloped
      with glycoproteins derived from Semliki Forest virus.
AB  - Lentiviruses have recently attracted considerable interest for their potential as
      a genetic modification tool for dendritic cells (DCs). In this study, we explore
      the ability of lentiviruses enveloped with alphaviral envelope glycoproteins
      derived from Semliki Forest virus (SFV) to mediate transduction of DCs. We found
      that SFV glycoprotein (SFV-G)-pseudotyped lentiviruses use C-type lectins (DC
      SIGN and L-SIGN) as attachment factors for transduction of DCs. Importantly, SFV
      G pseudotypes appear to have enhanced transduction towards C-type lectin
      expressing cells when produced under conditions limiting glycosylation to simple
      high-mannose, N-linked glycans. These results, in addition to the natural DC
      tropism of SFV-G, offer evidence to support the use of SFV-G-bearing lentiviruses
      to genetically modify DCs for the study of DC biology and DC-based immunotherapy.

PMID- 21738681
TI  - Elevated expression of stromal palladin predicts poor clinical outcome in renal
      cell carcinoma.
AB  - The role that stromal renal cell carcinoma (RCC) plays in support of tumor
      progression is unclear. Here we sought to determine the predictive value on
      patient survival of several markers of stromal activation and the feasibility of
      a fibroblast-derived extracellular matrix (ECM) based three-dimensional (3D)
      culture stemming from clinical specimens to recapitulate stromal behavior in
      vitro. The clinical relevance of selected stromal markers was assessed using a
      well annotated tumor microarray where stromal-marker levels of expression were
      evaluated and compared to patient outcomes. Also, an in vitro 3D system derived
      from fibroblasts harvested from patient matched normal kidney, primary RCC and
      metastatic tumors was employed to evaluate levels and localizations of known
      stromal markers such as the actin binding proteins palladin, alpha-smooth muscle
      actin (alpha-SMA), fibronectin and its spliced form EDA. Results suggested that
      RCCs exhibiting high levels of stromal palladin correlate with a poor prognosis,
      as demonstrated by overall survival time. Conversely, cases of RCCs where stroma
      presents low levels of palladin expression indicate increased survival times and,
      hence, better outcomes. Fibroblast-derived 3D cultures, which facilitate the
      categorization of stromal RCCs into discrete progressive stromal stages, also
      show increased levels of expression and stress fiber localization of alpha-SMA
      and palladin, as well as topographical organization of fibronectin and its splice
      variant EDA. These observations are concordant with expression levels of these
      markers in vivo. The study proposes that palladin constitutes a useful marker of
      poor prognosis in non-metastatic RCCs, while in vitro 3D cultures accurately
      represent the specific patient's tumor-associated stromal compartment. Our
      observations support the belief that stromal palladin assessments have clinical
      relevance thus validating the use of these 3D cultures to study both progressive
      RCC-associated stroma and stroma-dependent mechanisms affecting tumorigenesis.
      The clinical value of assessing RCC stromal activation merits further study.

PMID- 21738682
TI  - Rapid analysis of Listeria monocytogenes cell wall teichoic acid carbohydrates by
      ESI-MS/MS.
AB  - We report the application of electrospray ionization (ESI) mass spectrometry for
      compositional characterization of wall teichoic acids (WTA), a major component of
      gram-positive bacterial cell walls. Tandem mass spectrometry (ESI-MS/MS) of
      purified and chemically hydrolyzed monomeric WTA components provided sufficient
      information to identify WTA monomers and their specific carbohydrate
      constituents. A lithium matrix was used for ionization of uncharged WTA monomers,
      and successfully applied to analyze the WTA molecules of four Listeria strains
      differing in carbohydrate substitution on a conserved polyribitol-phosphate
      backbone structure. Carbohydrate residues such as N-acetylglucosamine or rhamnose
      linked to the WTA could directly be identified by ESI-MS/MS, circumventing the
      need for quantitative analysis by gas chromatography. The presence of a terminal
      N-acetylglucosamine residue tethered to the ribitol was confirmed using
      fluorescently labeled wheat-germ agglutinin. In conclusion, the mass spectrometry
      method described here will greatly facilitate compositional analysis and
      characterization of teichoic acids and similar macromolecules from diverse
      bacterial species, and represents a significant advance in the identification of
      serovar-specific carbohydrates and sugar molecules on bacteria.

PMID- 21738683
TI  - Localisation of human papillomavirus 16 E7 oncoprotein changes with cell
      confluence.
AB  - E7 is one of the best studied proteins of human papillomavirus type 16, largely
      because of its oncogenic potential linked to cervical cancer. Yet the sub
      cellular location of E7 remains confounding, even though it has been shown to be
      able to shuttle between the nucleus and the cytoplasm. Here we show with
      immunocytochemistry that E7 proteins are located in the nucleus and cytoplasm in
      sub-confluent cells, but becomes cytoplasmic in confluent cells. The change in
      E7's location is independent of time in culture, cell division, cell cycle phase
      or cellular differentiation. Levels of E7 are also increased in confluent cells
      as determined by Western blotting. Our investigations have also uncovered how
      different analytical techniques influence the observation of where E7 is
      localised, highlighting the importance of technical choice in such analysis.
      Understanding the localisation of E7 will help us to better comprehend the
      function of E7 on its target proteins.

PMID- 21738684
TI  - Biogeographical consequences of Cenozoic tectonic events within East Asian
      margins: a case study of Hynobius biogeography.
AB  - Few studies have explored the role of Cenozoic tectonic evolution in shaping
      patterns and processes of extant animal distributions within East Asian margins.
      We select Hynobius salamanders (Amphibia: Hynobiidae) as a model to examine
      biogeographical consequences of Cenozoic tectonic events within East Asian
      margins. First, we use GenBank molecular data to reconstruct phylogenetic
      interrelationships of Hynobius by bayesian and maximum likelihood analyses.
      Second, we estimate the divergence time using the bayesian relaxed clock approach
      and infer dispersal/vicariance histories under the 'dispersal-extinction
      cladogenesis' model. Finally, we test whether evolutionary history and
      biogeographical processes of Hynobius should coincide with the predictions of two
      major hypotheses (the 'vicariance'/'out of southwestern Japan' hypothesis). The
      resulting phylogeny confirmed Hynobius as a monophyletic group, which could be
      divided into nine major clades associated with six geographical areas. Our
      results show that: (1) the most recent common ancestor of Hynobius was
      distributed in southwestern Japan and Hokkaido Island, (2) a sister taxon
      relationship between Hynobius retardatus and all remaining species was the
      results of a vicariance event between Hokkaido Island and southwestern Japan in
      the Middle Eocene, (3) ancestral Hynobius in southwestern Japan dispersed into
      the Taiwan Island, central China, 'Korean Peninsula and northeastern China' as
      well as northeastern Honshu during the Late Eocene-Late Miocene. Our findings
      suggest that Cenozoic tectonic evolution plays an important role in shaping
      disjunctive distributions of extant Hynobius within East Asian margins.

PMID- 21738685
TI  - A concerted HIF-1alpha/MT1-MMP signalling axis regulates the expression of the
      3BP2 adaptor protein in hypoxic mesenchymal stromal cells.
AB  - Increased plasticity, migratory and immunosuppressive abilities characterize
      mesenchymal stromal cells (MSC) which enable them to be active participants in
      the development of hypoxic solid tumours. Our understanding of the oncogenic
      adaptation of MSC to hypoxia however lacks the identification and
      characterization of specific biomarkers. In this study, we assessed the hypoxic
      regulation of 3BP2/SH3BP2 (Abl SH3-binding protein 2), an immune response
      adaptor/scaffold protein which regulates leukocyte differentiation and motility.
      Gene silencing of 3BP2 abrogated MSC migration in response to hypoxic cues and
      generation of MSC stably expressing the transcription factor hypoxia inducible
      factor 1alpha (HIF-1alpha) resulted in increased endogenous 3BP2 expression as
      well as cell migration. Analysis of the 3BP2 promoter sequence revealed only one
      potential HIF-1alpha binding site within the human but none in the murine
      sequence. An alternate early signalling cascade that regulated 3BP2 expression
      was found to involve membrane type-1 matrix metalloproteinase (MT1-MMP)
      transcriptional regulation which gene silencing abrogated 3BP2 expression in
      response to hypoxia. Collectively, we provide evidence for a concerted HIF
      1alpha/MT1-MMP signalling axis that explains the induction of adaptor protein
      3BP2 and which may link protein binding partners together and stimulate oncogenic
      MSC migration. These mechanistic observations support the potential for malignant
      transformation of MSC within hypoxic tumour stroma and may contribute to evasion
      of the immune system by a tumour.

PMID- 21738686
TI  - X chromosome inactivation and differentiation occur readily in ES cells doubly
      deficient for macroH2A1 and macroH2A2.
AB  - Macrohistones (mH2As) are unusual histone variants found exclusively in
      vertebrate chromatin. In mice, the H2afy gene encodes two splice variants,
      mH2A1.1 and mH2A1.2 and a second gene, H2afy2, encodes an additional mH2A2
      protein. Both mH2A isoforms have been found enriched on the inactive X chromosome
      (Xi) in differentiated mammalian female cells, and are incorporated into the
      chromatin of developmentally-regulated genes. To investigate the functional
      significance of mH2A isoforms for X chromosome inactivation (XCI), we produced
      male and female embryonic stem cell (ESC) lines with stably-integrated shRNA
      constructs that simultaneously target both mH2A1 and mH2A2. Surprisingly, we find
      that female ESCs deficient for both mH2A1 and mH2A2 readily execute and maintain
      XCI upon differentiation. Furthermore, male and female mH2A-deficient ESCs
      proliferate normally under pluripotency culture conditions, and respond to
      several standard differentiation procedures efficiently. Our results show that
      XCI can readily proceed with substantially reduced total mH2A content.

PMID- 21738687
TI  - Regulation of LRRK2 expression points to a functional role in human monocyte
      maturation.
AB  - Genetic variants of Leucine-Rich Repeat Kinase 2 (LRRK2) are associated with a
      significantly enhanced risk for Parkinson disease, the second most common human
      neurodegenerative disorder. Despite major efforts, our understanding of LRRK2
      biological function and regulation remains rudimentary. In the present study we
      analyze LRRK2 mRNA and protein expression in sub-populations of human peripheral
      blood mononuclear cells (PBMCs). LRRK2 mRNA and protein was found in circulating
      CD19(+) B cells and in CD14(+) monocytes, whereas CD4(+) and CD8(+) T cells were
      devoid of LRRK2 mRNA. Within CD14(+) cells the CD14(+)CD16(+) sub-population of
      monocytes exhibited high levels of LRRK2 protein, in contrast to CD14(+)CD16(-)
      cells. However both populations expressed LRRK2 mRNA. As CD14(+)CD16(+) cells
      represent a more mature subset of monocytes, we monitored LRRK2 expression after
      in vitro treatment with various stress factors known to induce monocyte
      activation. We found that IFN-gamma in particular robustly increased LRRK2 mRNA
      and protein levels in monocytes concomitant with a shift of CD14(+)CD16(-) cells
      towards CD14(+)CD16(+) cells. Interestingly, the recently described LRRK2
      inhibitor IN-1 attenuated this shift towards CD14(+)CD16(+) after IFN-gamma
      stimulation. Based on these findings we speculate that LRRK2 might have a role in
      monocyte maturation. Our results provide further evidence for the emerging role
      of LRRK2 in immune cells and regulation at the transcriptional and translational
      level. Our data might also reflect an involvement of peripheral and brain immune
      cells in the disease course of PD, in line with increasing awareness of the role
      of the immune system in PD.

PMID- 21738688
TI  - alpha1A-adrenergic receptor induces activation of extracellular signal-regulated
      kinase 1/2 through endocytic pathway.
AB  - G protein-coupled receptors (GPCRs) activate mitogen-activated protein kinases
      through a number of distinct pathways in cells. Increasing evidence has suggested
      that endosomal signaling has an important role in receptor signal transduction.
      Here we investigated the involvement of endocytosis in alpha(1A)-adrenergic
      receptor (alpha(1A)-AR)-induced activation of extracellular signal-regulated
      kinase 1/2 (ERK1/2). Agonist-mediated endocytic traffic of alpha(1A)-AR was
      assessed by real-time imaging of living, stably transfected human embryonic
      kidney 293A cells (HEK-293A). alpha(1A)-AR was internalized dynamically in cells
      with agonist stimulation, and actin filaments regulated the initial trafficking
      of alpha(1A)-AR. alpha(1A)-AR-induced activation of ERK1/2 but not p38 MAPK was
      sensitive to disruption of endocytosis, as demonstrated by 4 degrees C chilling,
      dynamin mutation and treatment with cytochalasin D (actin depolymerizing agent).
      Activation of protein kinase C (PKC) and C-Raf by alpha(1A)-AR was not affected
      by 4 degrees C chilling or cytochalasin D treatment. U73122 (a phospholipase C
      [PLC] inhibitor) and Ro 31-8220 (a PKC inhibitor) inhibited alpha(1B)-AR- but not
      alpha(1A)-AR-induced ERK1/2 activation. These data suggest that the endocytic
      pathway is involved in alpha(1A)-AR-induced ERK1/2 activation, which is
      independent of G(q)/PLC/PKC signaling.

PMID- 21738689
TI  - Speeding cis-trans regulation discovery by phylogenomic analyses coupled with
      screenings of an arrayed library of Arabidopsis transcription factors.
AB  - Transcriptional regulation is an important mechanism underlying gene expression
      and has played a crucial role in evolution. The number, position and interactions
      between cis-elements and transcription factors (TFs) determine the expression
      pattern of a gene. To identify functionally relevant cis-elements in gene
      promoters, a phylogenetic shadowing approach with a lipase gene (LIP1) was used.
      As a proof of concept, in silico analyses of several Brassicaceae LIP1 promoters
      identified a highly conserved sequence (LIP1 element) that is sufficient to drive
      strong expression of a reporter gene in planta. A collection of ca. 1,200
      Arabidopsis thaliana TF open reading frames (ORFs) was arrayed in a 96-well
      format (RR library) and a convenient mating based yeast one hybrid (Y1H)
      screening procedure was established. We constructed an episomal plasmid (pTUY1H)
      to clone the LIP1 element and used it as bait for Y1H screenings. A novel
      interaction with an HD-ZIP (AtML1) TF was identified and abolished by a 2 bp
      mutation in the LIP1 element. A role of this interaction in transcriptional
      regulation was confirmed in planta. In addition, we validated our strategy by
      reproducing the previously reported interaction between a MYB-CC (PHR1) TF, a
      central regulator of phosphate starvation responses, with a conserved promoter
      fragment (IPS1 element) containing its cognate binding sequence. Finally, we
      established that the LIP1 and IPS1 elements were differentially bound by HD-ZIP
      and MYB-CC family members in agreement with their genetic redundancy in planta.
      In conclusion, combining in silico analyses of orthologous gene promoters with
      Y1H screening of the RR library represents a powerful approach to decipher cis-
      and trans-regulatory codes.

PMID- 21738690
TI  - MTF-1-mediated repression of the zinc transporter Zip10 is alleviated by zinc
      restriction.
AB  - The regulation of cellular zinc uptake is a key process in the overall mechanism
      governing mammalian zinc homeostasis and how zinc participates in cellular
      functions. We analyzed the zinc transporters of the Zip family in both the brain
      and liver of zinc-deficient animals and found a large, significant increase in
      Zip10 expression. Additionally, Zip10 expression decreased in response to zinc
      repletion. Moreover, isolated mouse hepatocytes, AML12 hepatocytes, and Neuro 2A
      cells also respond differentially to zinc availability in vitro. Measurement of
      Zip10 hnRNA and actinomycin D inhibition studies indicate that Zip10 was
      transcriptionally regulated by zinc deficiency. Through luciferase promoter
      constructs and ChIP analysis, binding of MTF-1 to a metal response element
      located 17 bp downstream of the transcription start site was shown to be
      necessary for zinc-induced repression of Zip10. Furthermore, zinc-activated MTF-1
      causes down-regulation of Zip10 transcription by physically blocking Pol II
      movement through the gene. Lastly, ZIP10 is localized to the plasma membrane of
      hepatocytes and neuro 2A cells. Collectively, these results reveal a novel
      repressive role for MTF-1 in the regulation of the Zip10 zinc transporter
      expression by pausing Pol II transcription. ZIP10 may have roles in control of
      zinc homeostasis in specific sites particularly those of the brain and liver.
      Within that context ZIP10 may act as an important survival mechanism during
      periods of zinc inadequacy.

PMID- 21738691
TI  - Long-term coexistence of rotifer cryptic species.
AB  - Despite their high morphological similarity, cryptic species often coexist in
      aquatic habitats presenting a challenge in the framework of niche differentiation
      theory and coexistence mechanisms. Here we use a rotifer species complex
      inhabiting highly unpredictable and fluctuating salt lakes to gain insights into
      the mechanisms involved in stable coexistence in cryptic species. We combined
      molecular barcoding surveys of planktonic populations and paleogenetic analysis
      of diapausing eggs to reconstruct the current and historical coexistence dynamics
      of two highly morphologically similar rotifer species, B. plicatilis and B.
      manjavacas. In addition, we carried out laboratory experiments using clones
      isolated from eight lakes where both species coexist to explore their clonal
      growth responses to salinity, a challenging, highly variable and unpredictable
      condition in Mediterranean salt lakes. We show that both species have co-occurred
      in a stable way in one lake, with population fluctuations in which no species was
      permanently excluded. The seasonal occurrence patterns of the plankton in two
      lakes agree with laboratory experiments showing that both species differ in their
      optimal salinity. These results suggest that stable species coexistence is
      mediated by differential responses to salinity and its fluctuating regime. We
      discuss the role of fluctuating salinity and a persistent diapausing egg banks as
      a mechanism for species coexistence in accordance with the 'storage effect'.

PMID- 21738692
TI  - Endoplasmic reticulum stress-induced JNK activation is a critical event leading
      to mitochondria-mediated cell death caused by beta-lapachone treatment.
AB  - BACKGROUND: beta-Lapachone (beta-lap) is a bioreductive agent that is activated
      by the two-electron reductase NAD(P)H quinone oxidoreductase 1 (NQO1). Although
      beta-lap has been reported to induce apoptosis in various cancer types in an NQO1
      dependent manner, the signaling pathways by which beta-lap causes apoptosis are
      poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: beta-Lap-induced apoptosis and
      related molecular signaling pathways in NQO1-negative and NQO1-overexpressing MDA
      MB-231 cells were investigated. Pharmacological inhibitors or siRNAs against
      factors involved in beta-lap-induced apoptosis were used to clarify the roles
      played by such factors in beta-lap-activated apoptotic signaling pathways. beta
      Lap leads to clonogenic cell death and apoptosis in an NQO1-dependent manner.
      Treatment of NQO1-overexpressing MDA-MB-231 cells with beta-lap causes rapid
      disruption of mitochondrial membrane potential, nuclear translocation of AIF and
      Endo G from mitochondria, and subsequent caspase-independent apoptotic cell
      death. siRNAs targeting AIF and Endo G effectively attenuate beta-lap-induced
      clonogenic and apoptotic cell death. Moreover, beta-lap induces cleavage of Bax,
      which accumulates in mitochondria, coinciding with the observed changes in
      mitochondria membrane potential. Pretreatment with Salubrinal (Sal), an
      endoplasmic reticulum (ER) stress inhibitor, efficiently attenuates JNK
      activation caused by beta-lap, and subsequent mitochondria-mediated cell death.
      In addition, beta-lap-induced generation and mitochondrial translocation of
      cleaved Bax are efficiently blocked by JNK inhibition. CONCLUSIONS/SIGNIFICANCE:
      Our results indicate that beta-lap triggers induction of endoplasmic reticulum
      (ER) stress, thereby leading to JNK activation and mitochondria-mediated
      apoptosis. The signaling pathways that we revealed in this study may
      significantly contribute to an improvement of NQO1-directed tumor therapies.

PMID- 21738693
TI  - Comparison of endothelial progenitor cells in Parkinson's disease patients
      treated with levodopa and levodopa/COMT inhibitor.
AB  - BACKGROUND: Levodopa treatment in Parkinson's disease (PD) increases in serum
      homocysteine levels due to its metabolism via catechol O-methyltransferase.
      Endothelial progenitor cells (EPCs) have the capacity to differentiate into
      mature endothelial cells and are markers for endothelial functions and
      cardiovascular risks. Along with traditional vascular risk factors,
      hyperhomocysteinemia is known to decrease the level of EPCs. In the present
      study, we hypothesized that that levodopa-induced hyperhomocysteinemia leads to a
      change in EPC levels. METHODOLOGY/PRINCIPAL FINDINGS: We prospectively enrolled
      PD patients who had been prescribed either levodopa/carbidopa (PD-L group, n =
      28) or levodopa/carbidopa/COMT inhibitor (PD-LC group, n = 25) for more than 1
      year. The number of circulating EPCs was measured by flow cytometry using dual
      staining of anti-CD34 and anti-KDR antibodies. The EPCs were divided into
      tertiles based on their distributions and a logistic regression analysis was used
      to estimate independent predictors of the highest tertile of EPCs. The number of
      endothelial progenitor cells was significantly decreased in PD-L patients (118+/
      99/mL) compared with either PD-LC patients (269+/-258/mL, p = 0.007) or controls
      (206+/-204/mL, p = 0.012). The level of homocysteine was significantly increased
      in PD-L patients (14.9+/-5.3 umol/L) compared with either PD-LC patients (11.9+/
      3.0 umol/L, p = 0.028) or controls (11.1+/-2.5 umol/L, p = 0.012). The level of
      homocysteine was negatively correlated with endothelial progenitor cell levels (r
      = -0.252, p = 0.028) and was an independent predictor of the highest tertile of
      endothelial progenitor cell levels (OR; 0.749 [95% CI: 0.584-0.961]).
      CONCLUSIONS/SIGNIFICANCE: These data indicate that a higher consumption of EPC
      for restoration of endothelial damage may be associated with chronic levodopa
      treatment in PD patients.

PMID- 21738694
TI  - Experimental evaluation of seed limitation in alpine snowbed plants.
AB  - BACKGROUND: The distribution and abundance of plants is controlled by the
      availability of seeds and of sites suitable for establishment. The relative
      importance of these two constraints is still contentious and possibly varies
      among species and ecosystems. In alpine landscapes, the role of seed limitation
      has traditionally been neglected, and the role of abiotic gradients emphasized.
      METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the importance of seed limitation
      for the incidence of four alpine snowbed species (Achillea atrata L., Achillea
      clusiana Tausch, Arabis caerulea L., Gnaphalium hoppeanum W. D. J. Koch) in local
      plant communities by comparing seedling emergence, seedling, juvenile and adult
      survival, juvenile and adult growth, flowering frequency as well as population
      growth rates lambda of experimental plants transplanted into snowbed patches
      which were either occupied or unoccupied by the focal species. In addition, we
      accounted for possible effects of competition or facilitation on these rates by
      including a measure of neighbourhood biomass into the analysis. We found that
      only A. caerulea had significantly lower seedling and adult survival as well as a
      lower population growth rate in unoccupied sites whereas the vital rates of the
      other three species did not differ among occupied and unoccupied sites. By
      contrast, all species were sensitive to competitive effects of the surrounding
      vegetation in terms of at least one of the studied rates.
      CONCLUSIONS/SIGNIFICANCE: We conclude that seed and site limitation jointly
      determine the species composition of these snowbed plant communities and that
      constraining site factors include both abiotic conditions and biotic
      interactions. The traditional focus on abiotic gradients for explaining alpine
      plant distribution hence appears lopsided. The influence of seed limitation on
      the current distribution of these plants casts doubt on their ability to readily
      track shifting habitats under climate change unless seed production is
      considerably enhanced under a warmer climate.

PMID- 21738695
TI  - Key amino acid residues of ankyrin-sensitive
      phosphatidylethanolamine/phosphatidylcholine-lipid binding site of betaI
      spectrin.
AB  - It was shown previously that an ankyrin-sensitive,
      phosphatidylethanolamine/phosphatidylcholine (PE/PC) binding site maps to the N
      terminal part of the ankyrin-binding domain of beta-spectrin (ankBDn). Here we
      have identified the amino acid residues within this domain which are responsible
      for recognizing monolayers and bilayers composed of PE/PC mixtures. In vitro
      binding studies revealed that a quadruple mutant with substituted hydrophobic
      residues W1771, L1775, M1778 and W1779 not only failed to effectively bind PE/PC,
      but its residual PE/PC-binding activity was insensitive to inhibition with
      ankyrin. Structure prediction and analysis, supported by in vitro experiments,
      suggests that "opening" of the coiled-coil structure underlies the mechanism of
      this interaction. Experiments on red blood cells and HeLa cells supported the
      conclusions derived from the model and in vitro lipid-protein interaction
      results, and showed the potential physiological role of this binding. We
      postulate that direct interactions between spectrin ankBDn and PE-rich domains
      play an important role in stabilizing the structure of the spectrin-based
      membrane skeleton.

PMID- 21738696
TI  - Grape seed proanthocyanidins inhibit melanoma cell invasiveness by reduction of
      PGE2 synthesis and reversal of epithelial-to-mesenchymal transition.
AB  - Melanoma is the leading cause of death from skin disease due, in large part, to
      its propensity to metastasize. We have examined the effect of grape seed
      proanthocyanidins (GSPs) on melanoma cancer cell migration and the molecular
      mechanisms underlying these effects using highly metastasis-specific human
      melanoma cell lines, A375 and Hs294t. Using in vitro cell invasion assays, we
      observed that treatment of A375 and Hs294t cells with GSPs resulted in a
      concentration-dependent inhibition of invasion or cell migration of these cells,
      which was associated with a reduction in the levels of cyclooxygenase (COX)-2
      expression and prostaglandin (PG) E(2) production. Treatment of cells with
      celecoxib, a COX-2 inhibitor, or transient transfection of melanoma cells with
      COX-2 small interfering RNA, also inhibited melanoma cell migration. Treatment of
      cells with 12-O-tetradecanoylphorbol-13-acetate, an inducer of COX-2, enhanced
      the phosphorylation of ERK1/2, a protein of mitogen-activated protein kinase
      family, and subsequently cell migration whereas both GSPs and celecoxib
      significantly inhibited 12-O-tetradecanoylphorbol-13-acetate-promoted cell
      migration as well as phosphorylation of ERK1/2. Treatment of cells with UO126, an
      inhibitor of MEK, also inhibited the migration of melanoma cells. Further, GSPs
      inhibited the activation of NF-kappaB/p65, an upstream regulator of COX-2, in
      melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an
      inhibitor of NF-kappaB, also inhibited cell migration. Additionally, inhibition
      of melanoma cell migration by GSPs was associated with reversal of epithelial
      mesenchymal transition process, which resulted in an increase in the levels of
      epithelial biomarkers (E-cadherin and cytokeratins) while loss of mesenchymal
      biomarkers (vimentin, fibronectin and N-cadherin) in melanoma cells. Together,
      these results indicate that GSPs have the ability to inhibit melanoma cell
      invasion/migration by targeting the endogenous expression of COX-2 and reversing
      the process of epithelial-to-mesenchymal transition.

PMID- 21738697
TI  - Increased frequency of spontaneous neoplastic transformation in progeny of
      bystander cells from cultures exposed to densely ionizing radiation.
AB  - An increased risk of carcinogenesis caused by exposure to space radiation during
      prolonged space travel is a limiting factor for human space exploration.
      Typically, astronauts are exposed to low fluences of ionizing particles that
      target only a few cells in a tissue at any one time. The propagation of stressful
      effects from irradiated to neighboring bystander cells and their transmission to
      progeny cells would be of importance in estimates of the health risks of exposure
      to space radiation. With relevance to the risk of carcinogenesis, we
      investigated, in model C3H 10T1/2 mouse embryo fibroblasts (MEFs), modulation of
      the spontaneous frequency of neoplastic transformation in the progeny of
      bystander MEFs that had been in co-culture 10 population doublings earlier with
      MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or
      sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic
      transformation frequency, likely mediated by intercellular communication through
      gap junctions, was observed in the progeny of bystander cells that had been in co
      culture with cells irradiated with iron ions, but not with protons.

PMID- 21738698
TI  - Gene networks and metacommunities: dispersal differences can override adaptive
      advantage.
AB  - Dispersal is an important mechanism contributing to both ecological and
      evolutionary dynamics. In metapopulation and metacommunity ecology, dispersal
      enables new patches to be colonized; in evolution, dispersal counter-acts local
      selection, leading to regional homogenization. Here, I consider a three-patch
      metacommunity in which two species, each with a limiting quantitative trait
      underlain by gene networks of 16 to 256 genes, compete with one another and
      disperse among patches. Incorporating dispersal among heterogeneous patches
      introduces a tradeoff not observed in single-patch simulations: if the difference
      between gene network size of the two species is greater than the difference in
      dispersal ability (e.g., if the ratio of network sizes is larger than the ratio
      of dispersal abilities), then genetic architecture drives community outcome.
      However, if the difference in dispersal abilities is greater than gene network
      differences, then any adaptive advantages afforded by genetic architecture are
      over-ridden by dispersal. Thus, in addition to the selective pressures imposed by
      competition that shape the genetic architecture of quantitative traits, dispersal
      among patches creates an escape that may further alter the effects of different
      genetic architectures. These results provide a theoretical expectation for what
      we may observe as the field of ecological genomics develops.

PMID- 21738699
TI  - Phasic phosphorylation of caldesmon and ERK 1/2 during contractions in human
      myometrium.
AB  - Human myometrium develops phasic contractions during labor. Phosphorylation of
      caldesmon (h-CaD) and extracellular signal-regulated kinase 1/2 (ERK 1/2) has
      been implicated in development of these contractions, however the phospho
      regulation of these proteins is yet to be examined during periods of both
      contraction and relaxation. We hypothesized that protein phosphorylation events
      are implicated in the phasic nature of myometrial contractions, and aimed to
      examine h-CaD and ERK 1/2 phosphorylation in myometrium snap frozen at specific
      stages, including; (1) prior to onset of contractions, (2) at peak contraction
      and (3) during relaxation. We aimed to compare h-CaD and ERK 1/2 phosphorylation
      in vitro against results from in vivo studies that compared not-in-labor (NIL)
      and laboring (L) myometrium. Comparison of NIL (n = 8) and L (n = 8) myometrium
      revealed a 2-fold increase in h-CaD phosphorylation (ser-789; P = 0.012) during
      onset of labor in vivo, and was associated with significantly up-regulated ERK2
      expression (P = 0.022), however no change in ERK2 phosphorylation was observed (P
      = 0.475). During in vitro studies (n = 5), transition from non-contracting tissue
      to tissue at peak contraction was associated with increased phosphorylation of
      both h-CaD and ERK 1/2. Furthermore, tissue preserved at relaxation phase
      exhibited diminished levels of h-CaD and ERK 1/2 phosphorylation compared to
      tissue preserved at peak contraction, thereby producing a phasic phosphorylation
      profile for h-CaD and ERK 1/2. h-CaD and ERK 1/2 are phosphorylated during
      myometrial contractions, however their phospho-regulation is dynamic, in that h
      CaD and ERK 1/2 are phosphorylated and dephosphorylated in phase with contraction
      and relaxation respectively. Comparisons of NIL and L tissue are at risk of
      failing to detect these changes, as L samples are not necessarily preserved in
      the midst of an active contraction.

PMID- 21738700
TI  - Mutation rate switch inside Eurasian mitochondrial haplogroups: impact of
      selection and consequences for dating settlement in Europe.
AB  - R-lineage mitochondrial DNA represents over 90% of the European population and is
      significantly present all around the planet (North Africa, Asia, Oceania, and
      America). This lineage played a major role in migration "out of Africa" and
      colonization in Europe. In order to determine an accurate dating of the R lineage
      and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences
      from Mitomap. This analysis revealed a new coalescence age for R at 54.500 years,
      as well as several limitations of standard dating methods, likely to lead to
      false interpretations. These findings highlight the association of a striking
      under-accumulation of synonymous mutations, an over-accumulation of non
      synonymous mutations, and the phenotypic effect on haplogroup J. Consequently,
      haplogroup J is apparently not a Neolithic group but an older haplogroup
      (Paleolithic) that was subjected to an underestimated selective force. These
      findings also indicated an under-accumulation of synonymous and non-synonymous
      mutations localized on coding and non-coding (HVS1) sequences for haplogroup R0,
      which contains the major haplogroups H and V. These new dates are likely to
      impact the present colonization model for Europe and confirm the late glacial
      resettlement scenario.

PMID- 21738701
TI  - Mitochondrial pathway mediates the antileukemic effects of Hemidesmus indicus, a
      promising botanical drug.
AB  - BACKGROUND: Although cancers are characterized by the deregulation of multiple
      signalling pathways, most current anticancer therapies involve the modulation of
      a single target. Because of the enormous biological diversity of cancer,
      strategic combination of agents targeted against the most critical of those
      alterations is needed. Due to their complex nature, plant products interact with
      numerous targets and influence several biochemical and molecular cascades. The
      interest in further development of botanical drugs has been increasing steadily
      and the FDA recently approved the first new botanical prescription drug. The
      present study is designed to explore the potential antileukemic properties of
      Hemidesmus indicus with a view to contributing to further development of
      botanical drugs. Hemidesmus was submitted to an extensive in vitro preclinical
      evaluation. METHODOLOGY/PRINCIPAL FINDINGS: A variety of cellular assays and flow
      cytometry, as well as a phytochemical screening, were performed on different
      leukemic cell lines. We have demonstrated that Hemidesmus modulated many
      components of intracellular signaling pathways involved in cell viability and
      proliferation and altered the protein expression, eventually leading to tumor
      cell death, mediated by a loss of mitochondrial transmembrane potential and
      increased Bax/Bcl-2 ratio. ADP, adenine nucleotide translocator and mitochondrial
      permeability transition pore inhibitors did not reverse Hemidesmus-induced
      mitochondrial depolarization. Hemidesmus induced a significant [Ca(2+)](i) raise
      through the mobilization of intracellular Ca(2+) stores. Moreover, Hemidesmus
      significantly enhanced the antitumor activity of three commonly used
      chemotherapeutic drugs (methotrexate, 6-thioguanine, cytarabine). A clinically
      relevant observation is that its cytotoxic activity was also recorded in primary
      cells from acute myeloid leukemic patients. CONCLUSIONS/SIGNIFICANCE: These
      results indicate the molecular basis of the antileukemic effects of Hemidesmus
      and identify the mitochondrial pathways and [Ca(2+)](i) as crucial actors in its
      anticancer activity. On these bases, we conclude that Hemidesmus can represent a
      valuable tool in the anticancer pharmacology, and should be considered for
      further investigations.

PMID- 21738702
TI  - The reality of Neandertal symbolic behavior at the Grotte du Renne, Arcy-sur
      Cure, France.
AB  - BACKGROUND: The question of whether symbolically mediated behavior is exclusive
      to modern humans or shared with anatomically archaic populations such as the
      Neandertals is hotly debated. At the Grotte du Renne, Arcy-sur-Cure, France, the
      Chatelperronian levels contain Neandertal remains and large numbers of personal
      ornaments, decorated bone tools and colorants, but it has been suggested that
      this association reflects intrusion of the symbolic artifacts from the overlying
      Protoaurignacian and/or of the Neandertal remains from the underlying Mousterian.
      METHODOLOGY/PRINCIPAL FINDINGS: We tested these hypotheses against the horizontal
      and vertical distributions of the various categories of diagnostic finds and
      statistically assessed the probability that the Chatelperronian levels are of
      mixed composition. Our results reject that the associations result from large or
      small scale, localized or generalized post-depositional displacement, and they
      imply that incomplete sample decontamination is the parsimonious explanation for
      the stratigraphic anomalies seen in the radiocarbon dating of the sequence.
      CONCLUSIONS/SIGNIFICANCE: The symbolic artifacts in the Chatelperronian of the
      Grotte du Renne are indeed Neandertal material culture.

PMID- 21738703
TI  - Mucoadhesive nanoparticles may disrupt the protective human mucus barrier by
      altering its microstructure.
AB  - Mucus secretions typically protect exposed surfaces of the eyes and respiratory,
      gastrointestinal and female reproductive tracts from foreign entities, including
      pathogens and environmental ultrafine particles. We hypothesized that excess
      exposure to some foreign particles, however, may cause disruption of the mucus
      barrier. Many synthetic nanoparticles are likely to be mucoadhesive due to
      hydrophobic, electrostatic or hydrogen bonding interactions. We therefore sought
      to determine whether mucoadhesive particles (MAP) could alter the mucus
      microstructure, thereby allowing other foreign particles to more easily penetrate
      mucus. We engineered muco-inert probe particles 1 um in diameter, whose diffusion
      in mucus is limited only by steric obstruction from the mucus mesh, and used them
      to measure possible MAP-induced changes to the microstructure of fresh human
      cervicovaginal mucus. We found that a 0.24% w/v concentration of 200 nm MAP in
      mucus induced a ~10-fold increase in the average effective diffusivity of the
      probe particles, and a 2- to 3-fold increase in the fraction capable of
      penetrating physiologically thick mucus layers. The same concentration of muco
      inert particles, and a low concentration (0.0006% w/v) of MAP, had no detectable
      effect on probe particle penetration rates. Using an obstruction-scaling model,
      we determined that the higher MAP dose increased the average mesh spacing ("pore"
      size) of mucus from 380 nm to 470 nm. The bulk viscoelasticity of mucus was
      unaffected by MAP exposure, suggesting MAP may not directly impair mucus
      clearance or its function as a lubricant, both of which depend critically on the
      bulk rheological properties of mucus. Our findings suggest mucoadhesive
      nanoparticles can substantially alter the microstructure of mucus, highlighting
      the potential of mucoadhesive environmental or engineered nanoparticles to
      disrupt mucus barriers and cause greater exposure to foreign particles, including
      pathogens and other potentially toxic nanomaterials.

PMID- 21738704
TI  - Epithelial to mesenchymal transition by TGFbeta-1 induction increases stemness
      characteristics in primary non small cell lung cancer cell line.
AB  - BACKGROUND: Cancer Stem Cells (CSCs) hypothesis asserts that only a small subset
      of cells within a tumour is capable of both tumour initiation and sustainment.
      The Epithelial-Mesenchymal Transition (EMT) is an embryonic developmental program
      that is often activated during cancer invasion and metastasis. The aim of this
      study is to shed light on the relationship between EMT and CSCs by using LC31
      lung cancer primary cell line. MATERIALS AND METHODS: A549 and LC31 cell lines
      were treated with 2 ng/ml TGFbeta-1 for 30 days, and 80 days, respectively. To
      evaluate EMT, morphological changes were assessed by light microscopy,
      immunofluorescence and cytometry for following markers: cytokeratins, e-cadherin,
      CD326 (epithelial markers) and CD90, and vimentin (mesenchymal markers).
      Moreover, RT-PCR for Slug, Twist and beta-catenin genes were performed. On
      TGFbeta-1 treated and untreated LC31 cell lines, we performed stemness tests such
      as pneumospheres growth and stem markers expression such as Oct4, Nanog, Sox2, c
      kit and CD133. Western Blot for CD133 and tumorigenicity assays using NOD/SCID
      mice were performed. RESULTS: TGFbeta-1 treated LC31 cell line lost its
      epithelial morphology assuming a fibroblast-like appearance. The same results
      were obtained for the A549 cell line (as control). Immunofluorescence and
      cytometry showed up-regulation of vimentin and CD90 and down-regulation of
      cytocheratin, e-cadherin and CD326 in TGFbeta-1 treated LC31 and A549 cell lines.
      Slug, Twist and beta-catenin m-RNA transcripts were up-regulated in TGFbeta-1
      treated LC31 cell line confirming EMT. This cell line showed also over-expression
      of Oct4, Nanog, Sox2 and CD133, all genes of stemness. In addition, in TGFbeta-1
      treated LC31 cell line, an increased pneumosphere-forming capacity and tumours
      forming ability in NOD/SCID mice were detectable. CONCLUSIONS: The induction of
      EMT by TGFbeta-1 exposure, in primary lung cancer cell line results in the
      acquisition of mesenchymal profile and in the expression of stem cell markers.

PMID- 21738705
TI  - Regulation of mTORC1 signaling by pH.
AB  - BACKGROUND: Acidification of the cytoplasm and the extracellular environment is
      associated with many physiological and pathological conditions, such as intense
      exercise, hypoxia and tumourigenesis. Acidification affects important cellular
      functions including protein synthesis, growth, and proliferation. Many of these
      vital functions are controlled by mTORC1, a master regulator protein kinase that
      is activated by various growth-stimulating signals and inactivated by starvation
      conditions. Whether mTORC1 can also respond to changes in extracellular or
      cytoplasmic pH and play a role in limiting anabolic processes in acidic
      conditions is not known. METHODOLOGY/FINDINGS: We examined the effects of
      acidifying the extracellular medium from pH 7.4 to 6.4 on human breast carcinoma
      MCF-7 cells and immortalized mouse embryo fibroblasts. Decreasing the
      extracellular pH caused intracellular acidification and rapid, graded and
      reversible inhibition of mTORC1, assessed by measuring the phosphorylation of the
      mTORC1 substrate S6K. Fibroblasts deleted of the tuberous sclerosis complex TSC2
      gene, a major negative regulator of mTORC1, were unable to inhibit mTORC1 in
      acidic extracellular conditions, showing that the TSC1-TSC2 complex is required
      for this response. Examination of the major upstream pathways converging on the
      TSC1-TSC2 complex showed that Akt signaling was unaffected by pH but that the
      Raf/MEK/ERK pathway was inhibited. Inhibition of MEK with drugs caused only
      modest mTORC1 inhibition, implying that other unidentified pathways also play
      major roles. CONCLUSIONS: This study reveals a novel role for the TSC1/TSC2
      complex and mTORC1 in sensing variations in ambient pH. As a common feature of
      low tissue perfusion, low glucose availability and high energy expenditure,
      acidic pH may serve as a signal for mTORC1 to downregulate energy-consuming
      anabolic processes such as protein synthesis as an adaptive response to
      metabolically stressful conditions.

PMID- 21738706
TI  - Exposure to sublethal doses of fipronil and thiacloprid highly increases
      mortality of honeybees previously infected by Nosema ceranae.
AB  - BACKGROUND: The honeybee, Apis mellifera, is undergoing a worldwide decline whose
      origin is still in debate. Studies performed for twenty years suggest that this
      decline may involve both infectious diseases and exposure to pesticides. Joint
      action of pathogens and chemicals are known to threaten several organisms but the
      combined effects of these stressors were poorly investigated in honeybees. Our
      study was designed to explore the effect of Nosema ceranae infection on honeybee
      sensitivity to sublethal doses of the insecticides fipronil and thiacloprid.
      METHODOLOGY/FINDING: Five days after their emergence, honeybees were divided in 6
      experimental groups: (i) uninfected controls, (ii) infected with N. ceranae,
      (iii) uninfected and exposed to fipronil, (iv) uninfected and exposed to
      thiacloprid, (v) infected with N. ceranae and exposed 10 days post-infection
      (p.i.) to fipronil, and (vi) infected with N. ceranae and exposed 10 days p.i. to
      thiacloprid. Honeybee mortality and insecticide consumption were analyzed daily
      and the intestinal spore content was evaluated 20 days after infection. A
      significant increase in honeybee mortality was observed when N. ceranae-infected
      honeybees were exposed to sublethal doses of insecticides. Surprisingly,
      exposures to fipronil and thiacloprid had opposite effects on microsporidian
      spore production. Analysis of the honeybee detoxification system 10 days p.i.
      showed that N. ceranae infection induced an increase in glutathione-S-transferase
      activity in midgut and fat body but not in 7-ethoxycoumarin-O-deethylase
      activity. CONCLUSIONS/SIGNIFICANCE: After exposure to sublethal doses of fipronil
      or thiacloprid a higher mortality was observed in N. ceranae-infected honeybees
      than in uninfected ones. The synergistic effect of N. ceranae and insecticide on
      honeybee mortality, however, did not appear strongly linked to a decrease of the
      insect detoxification system. These data support the hypothesis that the
      combination of the increasing prevalence of N. ceranae with high pesticide
      content in beehives may contribute to colony depopulation.

PMID- 21738707
TI  - Gain, loss and divergence in primate zinc-finger genes: a rich resource for
      evolution of gene regulatory differences between species.
AB  - The molecular changes underlying major phenotypic differences between humans and
      other primates are not well understood, but alterations in gene regulation are
      likely to play a major role. Here we performed a thorough evolutionary analysis
      of the largest family of primate transcription factors, the Kruppel-type zinc
      finger (KZNF) gene family. We identified and curated gene and pseudogene models
      for KZNFs in three primate species, chimpanzee, orangutan and rhesus macaque, to
      allow for a comparison with the curated set of human KZNFs. We show that the
      recent evolutionary history of primate KZNFs has been complex, including many
      lineage-specific duplications and deletions. We found 213 species-specific KZNFs,
      among them 7 human-specific and 23 chimpanzee-specific genes. Two human-specific
      genes were validated experimentally. Ten genes have been lost in humans and 13 in
      chimpanzees, either through deletion or pseudogenization. We also identified 30
      KZNF orthologs with human-specific and 42 with chimpanzee-specific sequence
      changes that are predicted to affect DNA binding properties of the proteins.
      Eleven of these genes show signatures of accelerated evolution, suggesting
      positive selection between humans and chimpanzees. During primate evolution the
      most extensive re-shaping of the KZNF repertoire, including most gene additions,
      pseudogenizations, and structural changes occurred within the subfamily
      homininae. Using zinc finger (ZNF) binding predictions, we suggest potential
      impact these changes have had on human gene regulatory networks. The large
      species differences in this family of TFs stands in stark contrast to the overall
      high conservation of primate genomes and potentially represents a potent driver
      of primate evolution.

PMID- 21738708
TI  - SMAC mimetic BV6 induces cell death in monocytes and maturation of monocyte
      derived dendritic cells.
AB  - BACKGROUND: Compounds mimicking the inhibitory effect of SMAC/DIABLO on X-linked
      inhibitor of apoptosis (XIAP) have been developed with the aim to achieve
      sensitization for apoptosis of tumor cells resistant due to deregulated XIAP
      expression. It turned out that SMAC mimetics also have complex effects on the
      NFkappaB system and TNF signaling. In view of the overwhelming importance of the
      NFkappaB transcription factors in the immune system, we analyzed here the effects
      of the SMAC mimetic BV6 on immune cells. PRINCIPAL FINDINGS: BV6 induced
      apoptotic and necrotic cell death in monocytes while T-cells, dendritic cells and
      macrophages were largely protected against BV6-induced cell death. In immature
      dendritic cells BV6 treatment resulted in moderate activation of the classical
      NFkappaB pathway, but it also diminished the stronger NFkappaB-inducing effect of
      TNF and CD40L. Despite its inhibitory effect on TNF- and CD40L signaling, BV6 was
      able to trigger maturation of immature DCs as indicated by upregulation of CD83,
      CD86 and IL12. SIGNIFICANCE: The demonstrated effects of SMAC mimetics on immune
      cells may complicate the development of tumor therapeutic concepts based on these
      compounds but also arise the possibility to exploit them for the development of
      immune stimulatory therapies.

PMID- 21738709
TI  - Study of camelpox virus pathogenesis in athymic nude mice.
AB  - Camelpox virus (CMLV) is the closest known orthopoxvirus genetically related to
      variola virus. So far, CMLV was restricted to camelids but, recently, three human
      cases of camelpox have been described in India, highlighting the need to pursue
      research on its pathogenesis, which has been hampered by the lack of small animal
      models. Here, we confirm that NMRI immunocompetent mice are resistant to
      intranasal (i.n.) CMLV infection. However, we demonstrate that CMLV induced a
      severe disease following i.n. challenge of athymic nude mice, which was
      accompanied with a failure in gaining weight, leading to euthanasia of the
      animals. On the other hand, intracutaneous (i.c.) infection resulted in disease
      development without impacting the body weight evolution. CMLV replication in
      tissues and body fluids was confirmed in the two models. We further analyzed
      innate immune and B cell responses induced in the spleen and draining lymph nodes
      after exposure to CMLV. In both models, strong increases in CD11b(+)F4/80(+)
      macrophages were seen in the spleen, while neutrophils, NK and B cell responses
      varied between the routes of infection. In the lymph nodes, the magnitude of
      CD11c(+)CD8alpha(+) lymphoid and CD11c(+)CD11b(+) myeloid dendritic cell
      responses increased in i.n. challenged animals. Analysis of cytokine profiles
      revealed significant increases of interleukin (IL)-6 and IL-18 in the sera of
      infected animals, while those of other cytokines were similar to uninfected
      controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6
      diaminopurine analog) was evaluated in both models. HPMPC was the most effective
      molecule affording 100% protection from morbidity. It appeared that both
      treatments did not affect immune cell responses or cytokine expression. In
      conclusion, we demonstrated that immunodeficient mice are permissive for CMLV
      propagation. These results provide a basis for studying the pathogenesis of CMLV,
      as well as for evaluating potential antiviral therapies in an immunodeficiency
      context.

PMID- 21738710
TI  - The age of the 20 meter Solo River terrace, Java, Indonesia and the survival of
      Homo erectus in Asia.
AB  - Homo erectus was the first human lineage to disperse widely throughout the Old
      World, the only hominin in Asia through much of the Pleistocene, and was likely
      ancestral to H. sapiens. The demise of this taxon remains obscure because of
      uncertainties regarding the geological age of its youngest populations. In 1996,
      some of us co-published electron spin resonance (ESR) and uranium series (U
      series) results indicating an age as young as 35-50 ka for the late H. erectus
      sites of Ngandong and Sambungmacan and the faunal site of Jigar (Indonesia). If
      correct, these ages favor an African origin for recent humans who would overlap
      with H. erectus in time and space. Here, we report (40)Ar/(39)Ar incremental
      heating analyses and new ESR/U-series age estimates from the "20 m terrace" at
      Ngandong and Jigar. Both data sets are internally consistent and provide no
      evidence for reworking, yet they are inconsistent with one another. The
      (40)Ar/(39)Ar analyses give an average age of 546+/-12 ka (sd+/-5 se) for both
      sites, the first reliable radiometric indications of a middle Pleistocene
      component for the terrace. Given the technical accuracy and consistency of the
      analyses, the argon ages represent either the actual age or the maximum age for
      the terrace and are significantly older than previous estimates. Most of the
      ESR/U-series results are older as well, but the oldest that meets all modeling
      criteria is 143 ka+20/-17. Most samples indicated leaching of uranium and likely
      represent either the actual or the minimum age of the terrace. Given known
      sources of error, the U-series results could be consistent with a middle
      Pleistocene age. However, the ESR and (40)Ar/(39)Ar ages preclude one another.
      Regardless, the age of the sites and hominins is at least bracketed between these
      estimates and is older than currently accepted.

PMID- 21738711
TI  - Genetic variants at 1p11.2 and breast cancer risk: a two-stage study in Chinese
      women.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified several breast
      cancer susceptibility loci, and one genetic variant, rs11249433, at 1p11.2 was
      reported to be associated with breast cancer in European populations. To explore
      the genetic variants in this region associated with breast cancer in Chinese
      women, we conducted a two-stage fine-mapping study with a total of 1792 breast
      cancer cases and 1867 controls. METHODOLOGY/PRINCIPAL FINDINGS: Seven single
      nucleotide polymorphisms (SNPs) including rs11249433 in a 277 kb region at 1p11.2
      were selected and genotyping was performed by using TaqMan(r) OpenArrayTM
      Genotyping System for stage 1 samples (878 cases and 900 controls). In stage 2
      (914 cases and 967 controls), three SNPs (rs2580520, rs4844616 and rs11249433)
      were further selected and genotyped for validation. The results showed that one
      SNP (rs2580520) located at a predicted enhancer region of SRGAP2 was consistently
      associated with a significantly increased risk of breast cancer in a recessive
      genetic model [Odds Ratio (OR)  =  1.66, 95% confidence interval (CI)  =  1.16
      2.36 for stage 2 samples; OR  =  1.51, 95% CI  =  1.16-1.97 for combined samples,
      respectively]. However, no significant association was observed between
      rs11249433 and breast cancer risk in this Chinese population (dominant genetic
      model in combined samples: OR  =  1.20, 95% CI  =  0.92-1.57).
      CONCLUSIONS/SIGNIFICANCE: Genotypes of rs2580520 at 1p11.2 suggest that Chinese
      women may have different breast cancer susceptibility loci, which may contribute
      to the development of breast cancer in this population.

PMID- 21738712
TI  - Resveratrol acts not through anti-aggregative pathways but mainly via its
      scavenging properties against Abeta and Abeta-metal complexes toxicity.
AB  - It has been recently suggested that resveratrol can be effective in slowing down
      Alzheimer's disease (AD) development. As reported in many biochemical studies,
      resveratrol seems to exert its neuro-protective role through inhibition of beta
      amyloid aggregation (Abeta), by scavenging oxidants and exerting anti
      inflammatory activities. In this paper, we demonstrate that resveratrol is
      cytoprotective in human neuroblastoma cells exposed to Abeta and or to Abeta
      metal complex. Our findings suggest that resveratrol acts not through anti
      aggregative pathways but mainly via its scavenging properties.

PMID- 21738713
TI  - Transcription regulation of sex-biased genes during ontogeny in the malaria
      vector Anopheles gambiae.
AB  - In Anopheles gambiae, sex-regulated genes are responsible for controlling gender
      dimorphism and are therefore crucial in determining the ability of female
      mosquitoes to transmit human malaria. The identification and functional
      characterization of these genes will shed light on the sexual development and
      maturation of mosquitoes and provide useful targets for genetic control measures
      aimed at reducing mosquito fertility and/or distorting the sex ratio.We conducted
      a genome wide transcriptional analysis of sex-regulated genes from early
      developmental stages through adulthood combined with functional screening of
      novel gonadal genes. Our results demonstrate that the male-biased genes undergo a
      major transcription turnover starting from larval stages to adulthood. The male
      biased genes at the adult stage include a significant high number of unique
      sequences compared to the rest of the genome. This is in contrast to female
      biased genes that are much more conserved and are mainly activated during late
      developmental stages.The high frequency of unique sequences would indicate that
      male-biased genes evolve more rapidly than the rest of the genome. This finding
      is particularly intriguing because A. gambiae is a strictly female monogamous
      species suggesting that driving forces in addition to sperm competition must
      account for the rapid evolution of male-biased genes. We have also identified and
      functionally characterized a number of previously unknown A. gambiae testis- and
      ovary-specific genes. Two of these genes, zero population growth and a suppressor
      of defective silencing 3 domain of the histone deacetylase co-repressor complex,
      were shown to play a key role in gonad development.

PMID- 21738714
TI  - Genetic dissection of epidermal growth factor receptor signaling during
      luteinizing hormone-induced oocyte maturation.
AB  - Recent evidence that luteinizing hormone (LH) stimulation of ovulatory follicles
      causes transactivation of the epidermal growth factor receptor (EGFR) has
      provided insights into the mechanisms of ovulation. However, the complete array
      of signals that promote oocyte reentry into the meiotic cell cycle in the
      follicle are still incompletely understood. To elucidate the signaling downstream
      of EGFR involved in oocyte maturation, we have investigated the LH responses in
      granulosa cells with targeted ablation of EGFR. Oocyte maturation and ovulation
      is disrupted when EGFR expression is progressively reduced. In granulosa cells
      from mice with either global or granulosa cell-specific disruption of EGFR
      signaling, LH-induced phosphorylation of MAPK3/1, p38MAPK, and connexin-43 is
      impaired. Although the LH-induced decrease in cGMP is EGFR-dependent in wild type
      follicles, LH still induces a decrease in cGMP in Egfr(delta/f) Cyp19-Cre
      follicles. Thus compensatory mechanisms appear activated in the mutant. Spatial
      propagation of the LH signal in the follicle also is dependent on the EGF
      network, and likely is important for the control of signaling to the oocyte.
      Thus, multiple signals and redundant pathways contribute to regulating oocyte
      reentry into the cell cycle.

PMID- 21738715
TI  - A reappraisal of the mechanism by which plant sterols promote neutral sterol loss
      in mice.
AB  - Dietary plant sterols (PS) reduce serum total and LDL-cholesterol in
      hyperlipidemic animal models and in humans. This hypocholesterolemic effect is
      generally ascribed to inhibition of cholesterol absorption. However, whether this
      effect fully explains the reported strong induction of neutral sterol excretion
      upon plant sterol feeding is not known. Recent data demonstrate that the
      intestine directly mediates plasma cholesterol excretion into feces, i.e.,
      without involvement of the hepato-biliary route. OBJECTIVE: Aim of this study was
      to determine whether stimulation of fecal neutral sterol loss during PS feeding
      is (partly) explained by increased intestinal cholesterol excretion and to assess
      the role of the cholesterol transporter Abcg5/Abcg8 herein. METHODS AND RESULTS:
      Wild-type mice were fed a control diet or diets enriched with increasing amounts
      of PS (1%, 2%, 4% or 8%, wt/wt) for two weeks. In addition, Abcg5(-/-) mice were
      fed either control or 8% PS diet. PS feeding resulted in a dose-dependent
      decrease of fractional cholesterol absorption (~2-7-fold reduction) in wild-type
      mice and ~80% reduction in Abcg5(-/-) mice. Furthermore, PS feeding led to a
      strong, dose-independent induction of neutral sterol excretion (3.4-fold in wild
      types and 2.7-fold in Abcg5(-/-) mice) without changes in biliary cholesterol
      secretion. It was calculated that PS feeding stimulated intestinal cholesterol
      excretion by ~500% in wild-type mice and by ~250% in Abcg5(-/-). CONCLUSIONS: Our
      data indicate that in mice the cholesterol-lowering effects of PS are to a large
      extent attributable to stimulation of intestinal, non-bile derived, cholesterol
      excretion. The Abcg5/Abcg8 heterodimer is involved in facilitating this PS
      induced flux of cholesterol.

PMID- 21738716
TI  - Whole genome sequencing and complete genetic analysis reveals novel pathways to
      glycopeptide resistance in Staphylococcus aureus.
AB  - The precise mechanisms leading to the emergence of low-level glycopeptide
      resistance in Staphylococcus aureus are poorly understood. In this study, we used
      whole genome deep sequencing to detect differences between two isogenic strains:
      a parental strain and a stable derivative selected stepwise for survival on 4
      ug/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 ug/ml).
      We uncovered only three single nucleotide changes in the selected strain.
      Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and
      in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol
      stress sensor and global transcriptional regulator, Spx. A missense mutation
      (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using
      genetic methods, all single, pairwise combinations, and a fully reconstructed
      triple mutant were evaluated for their contribution to low-level glycopeptide
      resistance. We found a synergistic cooperation between dual phospho-signalling
      systems and a subtle contribution from YjbH, suggesting the activation of
      oxidative stress defences via Spx. To our knowledge, this is the first genetic
      demonstration of multiple sensor and stress pathways contributing simultaneously
      to glycopeptide resistance development. The multifactorial nature of glycopeptide
      resistance in this strain suggests a complex reprogramming of cell physiology to
      survive in the face of drug challenge.

PMID- 21738717
TI  - Comparative genomics and transcriptomics of Propionibacterium acnes.
AB  - The anaerobic gram-positive bacterium Propionibacterium acnes is a human skin
      commensal that is occasionally associated with inflammatory diseases. Recent work
      has indicated that evolutionary distinct lineages of P. acnes play etiologic
      roles in disease while others are associated with maintenance of skin
      homeostasis. To shed light on the molecular basis for differential strain
      properties, we carried out genomic and transcriptomic analysis of distinct P.
      acnes strains. We sequenced the genome of the P. acnes strain 266, a type I-1a
      strain. Comparative genome analysis of strain 266 and four other P. acnes strains
      revealed that overall genome plasticity is relatively low; however, a number of
      island-like genomic regions, encoding a variety of putative virulence-associated
      and fitness traits differ between phylotypes, as judged from PCR analysis of a
      collection of P. acnes strains. Comparative transcriptome analysis of strains
      KPA171202 (type I-2) and 266 during exponential growth revealed inter-strain
      differences in gene expression of transport systems and metabolic pathways. In
      addition, transcript levels of genes encoding possible virulence factors such as
      dermatan-sulphate adhesin, polyunsaturated fatty acid isomerase, iron acquisition
      protein HtaA and lipase GehA were upregulated in strain 266. We investigated
      differential gene expression during exponential and stationary growth phases.
      Genes encoding components of the energy-conserving respiratory chain as well as
      secreted and virulence-associated factors were transcribed during the exponential
      phase, while the stationary growth phase was characterized by upregulation of
      genes involved in stress responses and amino acid metabolism. Our data highlight
      the genomic basis for strain diversity and identify, for the first time, the
      actively transcribed part of the genome, underlining the important role growth
      status plays in the inflammation-inducing activity of P. acnes. We argue that the
      disease-causing potential of different P. acnes strains is not only determined by
      the phylotype-specific genome content but also by variable gene expression.

PMID- 21738718
TI  - A minimum of three motifs is essential for optimal binding of pseudomurein cell
      wall-binding domain of Methanothermobacter thermautotrophicus.
AB  - We have biochemically and functionally characterized the pseudomurein cell wall
      binding (PMB) domain that is present at the C-terminus of the Surface (S)-layer
      protein MTH719 from Methanothermobacter thermautotrophicus. Chemical denaturation
      of the protein with guanidinium hydrochloride occurred at 3.8 M. A PMB-GFP fusion
      protein not only binds to intact pseudomurein of methanogenic archaea, but also
      to spheroplasts of lysozyme-treated bacterial cells. This binding is pH
      dependent. At least two of the three motifs that are present in the domain are
      necessary for binding. Limited proteolysis revealed a possible cleavage site in
      the spacing sequence between motifs 1 and 2 of the PMB domain, indicating that
      the motif region itself is protected from proteases.

PMID- 21738719
TI  - Acute hypoglycemia induces retinal cell death in mouse.
AB  - BACKGROUND: Glucose is the most important metabolic substrate of the retina and
      maintenance of normoglycemia is an essential challenge for diabetic patients.
      Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy
      and retinopathy. A vast body of literature exists on hyperglycemia namely in the
      field of diabetic retinopathy, but very little is known about the deleterious
      effect of hypoglycemia. Therefore, we decided to study the role of acute
      hypoglycemia in mouse retina. METHODOLOGY/PRINCIPAL FINDINGS: To test effects of
      hypoglycemia, we performed a 5-hour hyperinsulinemic/hypoglycemic clamp; to
      exclude an effect of insulin, we made a hyperinsulinemic/euglycemic clamp as
      control. We then isolated retinas from each group at different time-points after
      the clamp to analyze cells apoptosis and genes regulation. In parallel, we used
      661W photoreceptor cells to confirm in vivo results. We showed herein that
      hypoglycemia induced retinal cell death in mouse via caspase 3 activation. We
      then tested the mRNA expression of glutathione transferase omega 1 (Gsto1) and
      glutathione peroxidase 3 (Gpx3), two genes involved in glutathione (GSH)
      homeostasis. The expression of both genes was up-regulated by low glucose,
      leading to a decrease of reduced glutathione (GSH). In vitro experiments
      confirmed the low-glucose induction of 661W cell death via superoxide production
      and activation of caspase 3, which was concomitant with a decrease of GSH
      content. Moreover, decrease of GSH content by inhibition with buthionine
      sulphoximine (BSO) at high glucose induced apoptosis, while complementation with
      extracellular glutathione ethyl ester (GSHee) at low glucose restored GSH level
      and reduced apoptosis. CONCLUSIONS/SIGNIFICANCE: We showed, for the first time,
      that acute insulin-induced hypoglycemia leads to caspase 3-dependant retinal cell
      death with a predominant role of GSH content.

PMID- 21738720
TI  - On the representability of complete genomes by multiple competing finite-context
      (Markov) models.
AB  - A finite-context (Markov) model of order k yields the probability distribution of
      the next symbol in a sequence of symbols, given the recent past up to depth k.
      Markov modeling has long been applied to DNA sequences, for example to find gene
      coding regions. With the first studies came the discovery that DNA sequences are
      non-stationary: distinct regions require distinct model orders. Since then,
      Markov and hidden Markov models have been extensively used to describe the gene
      structure of prokaryotes and eukaryotes. However, to our knowledge, a
      comprehensive study about the potential of Markov models to describe complete
      genomes is still lacking. We address this gap in this paper. Our approach relies
      on (i) multiple competing Markov models of different orders (ii) careful
      programming techniques that allow orders as large as sixteen (iii) adequate
      inverted repeat handling (iv) probability estimates suited to the wide range of
      context depths used. To measure how well a model fits the data at a particular
      position in the sequence we use the negative logarithm of the probability
      estimate at that position. The measure yields information profiles of the
      sequence, which are of independent interest. The average over the entire
      sequence, which amounts to the average number of bits per base needed to describe
      the sequence, is used as a global performance measure. Our main conclusion is
      that, from the probabilistic or information theoretic point of view and according
      to this performance measure, multiple competing Markov models explain entire
      genomes almost as well or even better than state-of-the-art DNA compression
      methods, such as XM, which rely on very different statistical models. This is
      surprising, because Markov models are local (short-range), contrasting with the
      statistical models underlying other methods, where the extensive data repetitions
      in DNA sequences is explored, and therefore have a non-local character.

PMID- 21738721
TI  - The 3-base periodicity and codon usage of coding sequences are correlated with
      gene expression at the level of transcription elongation.
AB  - BACKGROUND: Gene transcription is regulated by DNA transcriptional regulatory
      elements, promoters and enhancers that are located outside the coding regions.
      Here, we examine the characteristic 3-base periodicity of the coding sequences
      and analyse its correlation with the genome-wide transcriptional profile of
      yeast. PRINCIPAL FINDINGS: The analysis of coding sequences by a new class of
      indices proposed here identified two different sources of 3-base periodicity: the
      codon frequency and the codon sequence. In exponentially growing yeast cells, the
      codon-frequency component of periodicity accounts for 71.9% of the variability of
      the cellular mRNA by a strong association with the density of elongating mRNA
      polymerase II complexes. The mRNA abundance explains most of the correlation
      between the codon-frequency component of periodicity and protein levels.
      Furthermore, pyrimidine-ending codons of the four-fold degenerate small amino
      acids alanine, glycine and valine are associated with genes with double the
      transcription rate of those associated with purine-ending codons. CONCLUSIONS: We
      demonstrate that the 3-base periodicity of coding sequences is higher than
      expected by the codon usage frequency (CUF) and that its components, associated
      with codon bias and amino acid composition, are correlated with gene expression,
      principally at the level of transcription elongation. This indicates a role of
      codon sequences in maximising the transcription efficiency in exponentially
      growing yeast cells. Moreover, the results contrast with the common darwinian
      explanation that attributes the codon bias to translational selection by an
      adjustment of synonymous codon frequencies to the most abundant isoaccepting
      tRNA. Here, we show that selection on codon bias likely acts at both the
      transcriptional and translational level and that codon usage and the relative
      abundance of tRNA could drive each other in order to synergistically optimize the
      efficiency of gene expression.

PMID- 21738722
TI  - Insulin promotes glycogen storage and cell proliferation in primary human
      astrocytes.
AB  - INTRODUCTION: In the human brain, there are at least as many astrocytes as
      neurons. Astrocytes are known to modulate neuronal function in several ways.
      Thus, they may also contribute to cerebral insulin actions. Therefore, we
      examined whether primary human astrocytes are insulin-responsive and whether
      their metabolic functions are affected by the hormone. METHODS: Commercially
      available Normal Human Astrocytes were grown in the recommended medium. Major
      players in the insulin signaling pathway were detected by real-time RT-PCR and
      Western blotting. Phosphorylation events were detected by phospho-specific
      antibodies. Glucose uptake and glycogen synthesis were assessed using radio
      labeled glucose. Glycogen content was assessed by histochemistry. Lactate levels
      were measured enzymatically. Cell proliferation was assessed by WST-1 assay.
      RESULTS: We detected expression of key proteins for insulin signaling, such as
      insulin receptor beta-subunit, insulin receptor substrat-1, Akt/protein kinase B
      and glycogen synthase kinase 3, in human astrocytes. Akt was phosphorylated and
      PI-3 kinase activity increased following insulin stimulation in a dose-dependent
      manner. Neither increased glucose uptake nor lactate secretion after insulin
      stimulation could be evidenced in this cell type. However, we found increased
      insulin-dependent glucose incorporation into glycogen. Furthermore, cell numbers
      increased dose-dependently upon insulin treatment. DISCUSSION: This study
      demonstrated that human astrocytes are insulin-responsive at the molecular level.
      We identified glycogen synthesis and cell proliferation as biological responses
      of insulin signaling in these brain cells. Hence, this cell type may contribute
      to the effects of insulin in the human brain.

PMID- 21738723
TI  - Changes in patch features may exacerbate or compensate for the effect of habitat
      loss on forest bird populations.
AB  - One and a half centuries after Darwin visited Chiloe Island, what he described as
      "...an island covered by one great forest..." has lost two-thirds of its forested
      areas. At this biodiversity hotspot, forest surface is becoming increasingly
      fragmented due to unregulated logging, clearing for pastures and replacement by
      exotic tree plantations. Decrease in patch size, increased isolation and "edge
      effects" can influence the persistence of forest species in remnant fragments. We
      assessed how these variables affect local density for six forest birds, chosen to
      include the most important seed dispersers (four species) and bird pollinators
      (two species, one of which acts also as seed disperser), plus the most common
      insectivore (Aphrastura spinicauda). Based on cue-count point surveys (8 points
      per fragment), we estimated bird densities for each species in 22 forest
      fragments of varying size, shape, isolation and internal-habitat structure (e.g.
      tree size and epiphyte cover). Bird densities varied with fragment connectivity
      (three species) and shape (three species), but none of the species was
      significantly affected by patch size. Satellite image analyses revealed that,
      from 1985 to 2008, forested area decreased by 8.8% and the remaining forest
      fragments became 16% smaller, 58-73% more isolated and 11-50% more regular.
      During that period, bird density estimates for the northern part of Chiloe
      (covering an area of 1214.75 km(2)) decreased for one species (elaenia),
      increased for another two (chucao and hummingbird) and did not vary for three
      (rayadito, thrust and blackbird). For the first three species, changes in patch
      features respectively exacerbated, balanced and overcame the effects of forest
      loss on bird population size (landscape-level abundance). Hence, changes in patch
      features can modulate the effect of habitat fragmentation on forest birds,
      suggesting that spatial planning (guided by spatially-explicit models) can be an
      effective tool to facilitate their conservation.

PMID- 21738724
TI  - The generation of live offspring from vitrified oocytes.
AB  - Oocyte cryopreservation is extremely beneficial for assisted reproductive
      technologies, the treatment of infertility and biotechnology and offers a viable
      alternative to embryo freezing and ovarian grafting approaches for the generation
      of embryonic stem cells and live offspring. It also offers the potential to store
      oocytes to rescue endangered species by somatic cell nuclear transfer and for the
      generation of embryonic stem cells to study development in these species. We
      vitrified mouse oocytes using a range of concentrations of trehalose (0 to 0.3 M)
      and demonstrated that 0.1 and 0.3 M trehalose had similar developmental rates,
      which were significantly different to the 0.2 M cohort (P<0.05). As mitochondria
      are important for fertilisation outcome, we observed that the clustering and
      distribution of mitochondria of the 0.2 M cohort were more affected by
      vitifrication than the other groups. Nevertheless, all 3 cohorts were able to
      develop to blastocyst, following in vitro fertilisation, although developmental
      rates were better for the 0.1 and 0.3 M cohorts than the 0.2 M cohort (P<0.05).
      Whilst blastocysts gave rise to embryonic stem-like cells, it was apparent from
      immunocytochemistry and RT-PCR that these cells did not demonstrate true
      pluripotency and exhibited abnormal karyotypes. However, they gave rise to
      teratomas following injection into SCID mice and differentiated into cells of
      each of the germinal layers following in vitro differentiation. The transfer of 2
      cell embryos from the 0.1 and 0.3 M cohorts resulted in the birth of live
      offspring that had normal karyotypes (9/10). When 2-cell embryos from vitrified
      oocytes underwent vitrification, and were thawed and transferred, live offspring
      were obtained that exhibited normal karyotypes, with the exception of one
      offspring who was larger and died at 7 months. We conclude that these studies
      highlight the importance of the endometrial environment for the maintenance of
      genetic stability and thus the propagation of specific genetic traits.

PMID- 21738725
TI  - Cognitive control in adolescence: neural underpinnings and relation to self
      report behaviors.
AB  - BACKGROUND: Adolescence is commonly characterized by impulsivity, poor decision
      making, and lack of foresight. However, the developmental neural underpinnings of
      these characteristics are not well established. METHODOLOGY/PRINCIPAL FINDINGS:
      To test the hypothesis that these adolescent behaviors are linked to under
      developed proactive control mechanisms, the present study employed a hybrid
      block/event-related functional Magnetic Resonance Imaging (fMRI) Stroop paradigm
      combined with self-report questionnaires in a large sample of adolescents and
      adults, ranging in age from 14 to 25. Compared to adults, adolescents under
      activated a set of brain regions implicated in proactive top-down control across
      task blocks comprised of difficult and easy trials. Moreover, the magnitude of
      lateral prefrontal activity in adolescents predicted self-report measures of
      impulse control, foresight, and resistance to peer pressure. Consistent with
      reactive compensatory mechanisms to reduced proactive control, older adolescents
      exhibited elevated transient activity in regions implicated in response-related
      interference resolution. CONCLUSIONS/SIGNIFICANCE: Collectively, these results
      suggest that maturation of cognitive control may be partly mediated by earlier
      development of neural systems supporting reactive control and delayed development
      of systems supporting proactive control. Importantly, the development of these
      mechanisms is associated with cognitive control in real-life behaviors.

PMID- 21738726
TI  - GPR54 (KISS1R) transactivates EGFR to promote breast cancer cell invasiveness.
AB  - Kisspeptins (Kp), peptide products of the Kisspeptin-1 (KISS1) gene are
      endogenous ligands for a G protein-coupled receptor 54 (GPR54). Previous findings
      have shown that KISS1 acts as a metastasis suppressor in numerous cancers in
      humans. However, recent studies have demonstrated that an increase in KISS1 and
      GPR54 expression in human breast tumors correlates with higher tumor grade and
      metastatic potential. At present, whether or not Kp signaling promotes breast
      cancer cell invasiveness, required for metastasis and the underlying mechanisms,
      is unknown. We have found that kisspeptin-10 (Kp-10), the most potent Kp,
      stimulates the invasion of human breast cancer MDA-MB-231 and Hs578T cells using
      Matrigel-coated Transwell chamber assays and induces the formation of invasive
      stellate structures in three-dimensional invasion assays. Furthermore, Kp-10
      stimulated an increase in matrix metalloprotease (MMP)-9 activity. We also found
      that Kp-10 induced the transactivation of epidermal growth factor receptor
      (EGFR). Knockdown of the GPCR scaffolding protein, beta-arrestin 2, inhibited Kp
      10-induced EGFR transactivation as well as Kp-10 induced invasion of breast
      cancer cells via modulation of MMP-9 secretion and activity. Finally, we found
      that the two receptors associate with each other under basal conditions, and FRET
      analysis revealed that GPR54 interacts directly with EGFR. The stability of the
      receptor complex formation was increased upon treatment of cells by Kp-10. Taken
      together, our findings suggest a novel mechanism by which Kp signaling via GPR54
      stimulates breast cancer cell invasiveness.

PMID- 21738727
TI  - Evolutionary constraints in hind wing shape in Chinese dung beetles (Coleoptera:
      Scarabaeinae).
AB  - This study examines the evolution hindwing shape in Chinese dung beetle species
      using morphometric and phylogenetic analyses. Previous studies have analyzed the
      evolution of wing shape within a single or very few species, or by comparing only
      a few wing traits. No study has analyzed wing shape evolution of a large number
      of species, or quantitatively compared morphological variation of wings with
      proposed phylogenetic relationships. This study examines the morphological
      variation of hindwings based on 19 landmarks, 119 morphological characters, and
      81 beetle species. Only one most parsimonious tree (MPT) was found based on 119
      wing and body characters. To better understand the possible role of the hindwing
      in the evolution of Scarabaeinae, additional phylogenetic analyses were proposed
      based on the only body features (106 characters, wing characters excluded). Two
      MPT were found based on 106 body characters, and five nodes were collapsed in a
      strict consensus. There was a strong correlation between the morphometric tree
      and all phylogenetic trees (r>0.5). Reconstructions of the ancestral wing forms
      suggest that Scarabaeinae hindwing morphology has not changed substantially over
      time, but the morphological changes that do occur are focused at the base of the
      wing. These results suggest that flight has been important since the origin of
      Scarabaeinae, and that variation in hindwing morphology has been limited by
      functional constraints. Comparison of metric disparity values and relative
      evolutionary sequences among Scarabaeinae tribes suggest that the primitive dung
      beetles had relatively diverse hindwing morphologies, while advanced dung beetles
      have relatively similar wing morphologies. The strong correlation between the
      morphometric tree and phylogenetic trees suggest that hindwing features reflect
      the evolution of whole body morphology and that wing characters are suitable for
      the phylogenetic analyses. By integrating morphometric and cladistic approaches,
      this paper sheds new light on the evolution of dung beetle hind wings.

PMID- 21738728
TI  - TSPYL2 is important for G1 checkpoint maintenance upon DNA damage.
AB  - Nucleosome assembly proteins play important roles in chromatin remodeling, which
      determines gene expression, cell proliferation and terminal differentiation.
      Testis specific protein, Y-encoded-like 2 (TSPYL2) is a nucleosome assembly
      protein expressed in neuronal precursors and mature neurons. Previous studies
      have shown that TSPYL2 binds cyclin B and inhibits cell proliferation in cultured
      cells suggesting a role in cell cycle regulation. To investigate the
      physiological significance of TSPYL2 in the control of cell cycle, we generated
      mice with targeted disruption of Tspyl2. These mutant mice appear grossly normal,
      have normal life span and do not exhibit increased tumor incidence. To define the
      role of TSPYL2 in DNA repair, checkpoint arrest and apoptosis, primary embryonic
      fibroblasts and thymocytes from Tspyl2 deficient mice were isolated and examined
      under unperturbed and stressed conditions. We show that mutant fibroblasts are
      impaired in G1 arrest under the situation of DNA damage induced by gamma
      irradiation. This is mainly attributed to the defective activation of p21
      transcription despite proper p53 protein accumulation, suggesting that TSPYL2 is
      additionally required for p21 induction. TSPYL2 serves a biological role in
      maintaining the G1 checkpoint under stress condition.

PMID- 21738729
TI  - Altered desaturation and elongation of fatty acids in hormone-sensitive lipase
      null mice.
AB  - BACKGROUND: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose
      tissue, where it plays an important role in catecholamine-stimulated hydrolysis
      of stored lipids, thus mobilizing fatty acids. HSL exhibits broad substrate
      specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl
      esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null
      mice have been shown to be resistant to diet-induced obesity. The aim of this
      study was to define lipid profiles in plasma, white adipose tissue (WAT) and
      liver of HSL null mice, in order to better understand the role of this
      multifunctional enzyme. METHODOLOGY/PRINCIPAL FINDINGS: This study used global
      and targeted lipidomics and expression profiling to reveal changed lipid profiles
      in WAT, liver and plasma as well as altered expression of desaturases and
      elongases in WAT and liver of HSL null mice on high fat diet. Decreased mRNA
      levels of stearoyl-CoA desaturase 1 and 2 in WAT were consistent with a lowered
      ratio of 16:1n7/16:0 and 18:1n9/18:0 in WAT and plasma. In WAT, increased ratio
      of 18:0/16:0 could be linked to elevated mRNA levels of the Elovl1 elongase.
      CONCLUSIONS: This study illustrates the importance of HSL for normal lipid
      metabolism in response to a high fat diet. HSL deficiency greatly influences the
      expression of elongases and desaturases, resulting in altered lipid profiles in
      WAT, liver and plasma. Finally, altered proportions of palmitoleate, a recently
      suggested lipokine, in tissue and plasma of HSL null mice, could be an important
      factor mediating and contributing to the changed lipid profile, and possibly also
      to the decreased insulin sensitivity seen in HSL null mice.

PMID- 21738730
TI  - Explicit-duration hidden Markov model inference of UP-DOWN states from continuous
      signals.
AB  - Neocortical neurons show UP-DOWN state (UDS) oscillations under a variety of
      conditions. These UDS have been extensively studied because of the insight they
      can yield into the functioning of cortical networks, and their proposed role in
      putative memory formation. A key element in these studies is determining the
      precise duration and timing of the UDS. These states are typically determined
      from the membrane potential of one or a small number of cells, which is often not
      sufficient to reliably estimate the state of an ensemble of neocortical neurons.
      The local field potential (LFP) provides an attractive method for determining the
      state of a patch of cortex with high spatio-temporal resolution; however current
      methods for inferring UDS from LFP signals lack the robustness and flexibility to
      be applicable when UDS properties may vary substantially within and across
      experiments. Here we present an explicit-duration hidden Markov model (EDHMM)
      framework that is sufficiently general to allow statistically principled
      inference of UDS from different types of signals (membrane potential, LFP, EEG),
      combinations of signals (e.g., multichannel LFP recordings) and signal features
      over long recordings where substantial non-stationarities are present. Using
      cortical LFPs recorded from urethane-anesthetized mice, we demonstrate that the
      proposed method allows robust inference of UDS. To illustrate the flexibility of
      the algorithm we show that it performs well on EEG recordings as well. We then
      validate these results using simultaneous recordings of the LFP and membrane
      potential (MP) of nearby cortical neurons, showing that our method offers
      significant improvements over standard methods. These results could be useful for
      determining functional connectivity of different brain regions, as well as
      understanding network dynamics.

PMID- 21738731
TI  - Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight
      respiratory viruses by real-time reverse transcription-PCR assays.
AB  - BACKGROUND: Many acute respiratory illness surveillance systems collect and test
      nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few
      studies assessing the relative measures of performance for NP versus OP
      specimens. METHODS: We collected paired NP and OP swabs separately from pediatric
      and adult patients with influenza-like illness or severe acute respiratory
      illness at two respiratory surveillance sites in Kenya. The specimens were tested
      for eight respiratory viruses by real-time reverse transcription-polymerase chain
      reaction (qRT-PCR). Positivity for a specific virus was defined as detection of
      viral nucleic acid in either swab. RESULTS: Of 2,331 paired NP/OP specimens,
      1,402 (60.1%) were positive for at least one virus, and 393 (16.9%) were positive
      for more than one virus. Overall, OP swabs were significantly more sensitive than
      NP swabs for adenovirus (72.4% vs. 57.6%, p<0.01) and 2009 pandemic influenza A
      (H1N1) virus (91.2% vs. 70.4%, p<0.01). NP specimens were more sensitive for
      influenza B virus (83.3% vs. 61.5%, p = 0.02), parainfluenza virus 2 (85.7%, vs.
      39.3%, p<0.01), and parainfluenza virus 3 (83.9% vs. 67.4%, p<0.01). The two
      methods did not differ significantly for human metapneumovirus, influenza A
      (H3N2) virus, parainfluenza virus 1, or respiratory syncytial virus. CONCLUSIONS:
      The sensitivities were variable among the eight viruses tested; neither specimen
      was consistently more effective than the other. For respiratory disease
      surveillance programs using qRT-PCR that aim to maximize sensitivity for a large
      number of viruses, collecting combined NP and OP specimens would be the most
      effective approach.

PMID- 21738732
TI  - Uncovering the profile of somatic mtDNA mutations in Chinese colorectal cancer
      patients.
AB  - In the past decade, a high incidence of somatic mitochondrial DNA (mtDNA)
      mutations has been observed, mostly based on a fraction of the molecule, in
      various cancerous tissues; nevertheless, some of them were queried due to
      problems in data quality. Obviously, without a comprehensive understanding of
      mtDNA mutational profile in the cancerous tissue of a specific patient, it is
      unlikely to disclose the genuine relationship between somatic mtDNA mutations and
      tumorigenesis. To achieve this objective, the most straightforward way is to
      directly compare the whole mtDNA genome variation among three tissues (namely,
      cancerous tissue, para-cancerous tissue, and distant normal tissue) from the same
      patient. Considering the fact that most of the previous studies on the role of
      mtDNA in colorectal tumor focused merely on the D-loop or partial segment of the
      molecule, in the current study we have collected three tissues (cancerous, para
      cancerous and normal tissues) respectively recruited from 20 patients with
      colorectal tumor and completely sequenced the mitochondrial genome of each
      tissue. Our results reveal a relatively lower incidence of somatic mutations in
      these patients; intriguingly, all somatic mutations are in heteroplasmic status.
      Surprisingly, the observed somatic mutations are not restricted to cancer
      tissues, for the para-cancer tissues and distant normal tissues also harbor
      somatic mtDNA mutations with a lower frequency than cancerous tissues but higher
      than that observed in the general population. Our results suggest that somatic
      mtDNA mutations in cancerous tissues could not be simply explained as a
      consequence of tumorigenesis; meanwhile, the somatic mtDNA mutations in normal
      tissues might reflect an altered physiological environment in cancer patients.

PMID- 21738733
TI  - The elusive third subunit IIa of the bacterial B-type oxidases: the enzyme from
      the hyperthermophile Aquifex aeolicus.
AB  - The reduction of molecular oxygen to water is catalyzed by complicated membrane
      bound metallo-enzymes containing variable numbers of subunits, called cytochrome
      c oxidases or quinol oxidases. We previously described the cytochrome c oxidase
      II from the hyperthermophilic bacterium Aquifex aeolicus as a ba(3)-type two
      subunit (subunits I and II) enzyme and showed that it is included in a
      supercomplex involved in the sulfide-oxygen respiration pathway. It belongs to
      the B-family of the heme-copper oxidases, enzymes that are far less studied than
      the ones from family A. Here, we describe the presence in this enzyme of an
      additional transmembrane helix "subunit IIa", which is composed of 41 amino acid
      residues with a measured molecular mass of 5105 Da. Moreover, we show that
      subunit II, as expected, is in fact longer than the originally annotated protein
      (from the genome) and contains a transmembrane domain. Using Aquifex aeolicus
      genomic sequence analyses, N-terminal sequencing, peptide mass fingerprinting and
      mass spectrometry analysis on entire subunits, we conclude that the B-type enzyme
      from this bacterium is a three-subunit complex. It is composed of subunit I
      (encoded by coxA(2)) of 59000 Da, subunit II (encoded by coxB(2)) of 16700 Da and
      subunit IIa which contain 12, 1 and 1 transmembrane helices respectively. A
      structural model indicates that the structural organization of the complex
      strongly resembles that of the ba(3) cytochrome c oxidase from the bacterium
      Thermus thermophilus, the IIa helical subunit being structurally the lacking N
      terminal transmembrane helix of subunit II present in the A-type oxidases.
      Analysis of the genomic context of genes encoding oxidases indicates that this
      third subunit is present in many of the bacterial oxidases from B-family, enzymes
      that have been described as two-subunit complexes.

PMID- 21738734
TI  - Histological observation of islet hemorrhage induced by diagnostic ultrasound
      with contrast agent in rat pancreas.
AB  - Contrast enhanced diagnostic ultrasound CEDUS has been shown to induce capillary
      hemorrhage in heart and kidney. This study characterized the capillary hemorrhage
      induced in rat pancreas. The pancreata of anesthetized hairless rats were
      accessed by laparotomy. A 1.5 MHz diagnostic ultrasound probe with 2.3 MPa peak
      rarefactional pressure amplitude and 1 s intermittent trigger was used to scan
      the pancreas, located at the focus (3.8 cm), through saline coupling. The probe
      was swept to expose the entire organ in 5 min during infusion of Definity(r)
      contrast agent at 10 uL/kg/min, and this was repeated in a reverse sweep. The
      entire pancreas was removed, spread flat for fixation and histological slides
      were prepared from the mid-plane. Slides were scored blind for islet hemorrhage
      over the entire area of the organ. Intra-islet microlesions were evident and
      hemorrhage surrounded many islets. The hemorrhage often impacted nearby acini,
      and expanded into inter-lobular septa. In CEDUS pancreata removed soon after
      scanning, 76.2+/-11.8% (n = 6) of islets had evidence of hemorrhage and/or islet
      microlesions compared to 1.1+/-2.5% (n = 5) for sham CEDUS (P<0.001). In
      pancreata removed after 4 hr, fibrin formation was detected by immunohistology in
      the hemorrhage and intra-islet microlesions. Diagnostic ultrasound with contrast
      agent induced substantial capillary hemorrhage in rat pancreas, concentrated
      particularly in the islets.

PMID- 21738735
TI  - iNOS ablation does not improve specific force of the extensor digitorum longus
      muscle in dystrophin-deficient mdx4cv mice.
AB  - Nitrosative stress compromises force generation in Duchenne muscular dystrophy
      (DMD). Both inducible nitric oxide synthase (iNOS) and delocalized neuronal NOS
      (nNOS) have been implicated. We recently demonstrated that genetic elimination of
      nNOS significantly enhanced specific muscle forces of the extensor digitorum
      longus (EDL) muscle of dystrophin-null mdx4cv mice (Li D et al J. Path. 223:88
      98, 2011). To determine the contribution of iNOS, we generated iNOS deficient
      mdx4cv mice. Genetic elimination of iNOS did not alter muscle histopathology.
      Further, the EDL muscle of iNOS/dystrophin DKO mice yielded specific twitch and
      tetanic forces similar to those of mdx4cv mice. Additional studies suggest iNOS
      ablation did not augment nNOS expression neither did it result in appreciable
      change of nitrosative stress markers in muscle. Our results suggest that iNOS may
      play a minor role in mediating nitrosative stress-associated force reduction in
      DMD.

PMID- 21738736
TI  - An automated paradigm for Drosophila visual psychophysics.
AB  - BACKGROUND: Mutations that cause learning and memory defects in Drosophila
      melanogaster have been found to also compromise visual responsiveness and
      attention. A better understanding of attention-like defects in such Drosophila
      mutants therefore requires a more detailed characterization of visual
      responsiveness across a range of visual parameters. METHODOLOGY/PRINCIPAL
      FINDINGS: We designed an automated behavioral paradigm for efficiently dissecting
      visual responsiveness in Drosophila. Populations of flies walk through
      multiplexed serial choice mazes while being exposed to moving visuals displayed
      on computer monitors, and infra-red fly counters at the end of each maze
      automatically score the responsiveness of a strain. To test our new design, we
      performed a detailed comparison between wild-type flies and a learning and memory
      mutant, dunce(1). We first confirmed that the learning mutant dunce(1) displays
      increased responsiveness to a black/green moving grating compared to wild type in
      this new design. We then extended this result to explore responses to a wide
      range of psychophysical parameters for moving gratings (e.g., luminosity,
      contrast, spatial frequency, velocity) as well as to a different stimulus, moving
      dots. Finally, we combined these visuals (gratings versus dots) in competition to
      investigate how dunce(1) and wild-type flies respond to more complex and
      conflicting motion effects. CONCLUSIONS/SIGNIFICANCE: We found that dunce(1)
      responds more strongly than wild type to high contrast and highly structured
      motion. This effect was found for simple gratings, dots, and combinations of both
      stimuli presented in competition.

PMID- 21738737
TI  - Physiological induction of regulatory Qa-1-restricted CD8+ T cells triggered by
      endogenous CD4+ T cell responses.
AB  - T cell-dependent autoimmune diseases are characterized by the expansion of T cell
      clones that recognize immunodominant epitopes on the target antigen. As a
      consequence, for a given autoimmune disorder, pathogenic T cell clones express T
      cell receptors with a limited number of variable regions that define antigenic
      specificity. Qa-1, a MHC class I-like molecule, presents peptides from the
      variable region of TCRs to Qa-1-restricted CD8+ T cells. The induction of Vbeta
      specific CD8+ T cells has been harnessed in an immunotherapeutic strategy known
      as the "T cell vaccination" (TCV) that comprises the injection of activated and
      attenuated CD4+ T cell clones so as to induce protective CD8+ T cells. We
      hypothesized that Qa-1-restricted CD8+ regulatory T cells could also constitute a
      physiologic regulatory arm of lymphocyte responses upon expansion of endogenous
      CD4+ T cells, in the absence of deliberate exogenous T cell vaccination. We
      immunized mice with two types of antigenic challenges in order to sequentially
      expand antigen-specific endogenous CD4+ T cells with distinct antigenic
      specificities but characterized by a common Vbeta chain in their TCR. The first
      immunization was performed with a non-self antigen while the second challenge was
      performed with a myelin-derived peptide known to drive experimental autoimmune
      encephalomyelitis (EAE), a mouse model of multiple sclerosis. We show that
      regulatory Vbeta-specific Qa-1-restricted CD8+ T cells induced during the first
      endogenous CD4+ T cell responses are able to control the expansion of
      subsequently mobilized pathogenic autoreactive CD4+ T cells. In conclusion, apart
      from the immunotherapeutic TCV, Qa-1-restricted specialized CD8+ regulatory T
      cells can also be induced during endogenous CD4+ T cell responses. At variance
      with other regulatory T cell subsets, the action of these Qa-1-restricted T cells
      seems to be restricted to the immediate re-activation of CD4+ T cells.

PMID- 21738738
TI  - Transmission of Fusarium boothii mycovirus via protoplast fusion causes
      hypovirulence in other phytopathogenic fungi.
AB  - There is increasing concern regarding the use of fungicides to control plant
      diseases, whereby interest has increased in the biological control of
      phytopathogenic fungi by the application of hypovirulent mycoviruses as a
      possible alternative to fungicides. Transmission of hypovirulence-associated
      double-stranded RNA (dsRNA) viruses between mycelia, however, is prevented by the
      vegetative incompatibility barrier that often exists between different species or
      strains of filamentous fungi. We determined whether protoplast fusion could be
      used to transmit FgV1-DK21 virus, which is associated with hypovirulence on F.
      boothii (formerly F. graminearum strain DK21), to F. graminearum, F. asiaticum,
      F. oxysporum f. sp. lycopersici, and Cryphonectria parasitica. Relative to virus
      free strains, the FgV1-DK21 recipient strains had reduced growth rates, altered
      pigmentation, and reduced virulence. These results indicate that protoplast
      fusion can be used to introduce FgV1-DK21 dsRNA into other Fusarium species and
      into C. parasitica and that FgV1-DK21 can be used as a hypovirulence factor and
      thus as a biological control agent.

PMID- 21738739
TI  - Effector and naturally occurring regulatory T cells display no abnormalities in
      activation induced cell death in NOD mice.
AB  - BACKGROUND: Disturbed peripheral negative regulation might contribute to
      evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the
      sensitivity of naive/effector (Teff) and regulatory T cells (Treg) to activation
      induced cell death mediated by Fas cross-linking in NOD and wild-type mice.
      PRINCIPAL FINDINGS: Both effector (CD25(-), FoxP3(-)) and suppressor (CD25(+),
      FoxP3(+)) CD4(+) T cells are negatively regulated by Fas cross-linking in mixed
      splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess.
      Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg
      cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg
      resistance to Fas-ligand (FasL) in both strains. The effector and suppressor
      CD4(+) subsets display balanced sensitivity to negative regulation under baseline
      conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not
      perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of
      diabetogenic cells was evident from delayed onset and reduced incidence of
      adoptive disease transfer into NOD.SCID by CD4(+)CD25(-) T cells decorated with
      FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive
      activity in vitro. The only detectable differential response was reduced Teff
      proliferation and upregulation of CD25 following CD3-activation in NOD mice.
      CONCLUSION: These data document negative regulation of effector and suppressor
      cells by Fas cross-linking and dissociation between sensitivity to apoptosis and
      proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD
      mice initiates or promotes autoimmune insulitis.

PMID- 21738740
TI  - Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome
      oncogenic PIK3CA resistance.
AB  - Documented sensitivity of melanoma cells to PLX4720, a selective BRAFV600E
      inhibitor, is based on the presence of mutant BRAF(V600E) alone, while wt-BRAF or
      mutated KRAS result in cell proliferation. In colon cancer appearance of
      oncogenic alterations is complex , since BRAF, like KRAS mutations, tend to co
      exist with those in PIK3CA and mutated PI3K has been shown to interfere with the
      successful application of MEK inhibitors. When PLX4720 was used to treat colon
      tumours, results were not encouraging and herein we attempt to understand the
      cause of this recorded resistance and discover rational therapeutic combinations
      to resensitize oncogene driven tumours to apoptosis. Treatment of two genetically
      different BRAF(V600E) mutant colon cancer cell lines with PLX4720 conferred
      complete resistance to cell death. Even though p-MAPK/ ERK kinase (MEK)
      suppression was achieved, TRAIL, an apoptosis inducing agent, was used
      synergistically in order to achieve cell death by apoptosis in
      RKO(BRAFV600E/PIK3CAH1047) cells. In contrast, for the same level of apoptosis in
      HT29(BRAFV600E/PIK3CAP449T) cells, TRAIL was combined with 17-AAG, an Hsp90
      inhibitor. For cells where PLX4720 was completely ineffective, 17-AAG was
      alternatively used to target mutant BRAF(V600E). TRAIL dependence on the
      constitutive activation of BRAF(V600E) is emphasised through the overexpression
      of BRAF(V600E) in the permissive genetic background of colon adenocarcinoma Caco
      2 cells. Pharmacological suppression of the PI3K pathway further enhances the
      synergistic effect between TRAIL and PLX4720 in RKO cells, indicating the
      presence of PIK3CA(MT) as the inhibitory factor. Another rational combination
      includes 17-AAG synergism with TRAIL in a BRAF(V600E) mutant dependent manner to
      commit cells to apoptosis, through DR5 and the amplification of the apoptotic
      pathway. We have successfully utilised combinations of two chemically unrelated
      BRAF(V600E) inhibitors in combination with TRAIL in a BRAF(V600E) mutated
      background and provided insight for new anti-cancer strategies where the
      activated PI3KCA mutation oncogene should be suppressed.

PMID- 21738741
TI  - SWI/SNF and Asf1 independently promote derepression of the DNA damage response
      genes under conditions of replication stress.
AB  - The histone chaperone Asf1 and the chromatin remodeler SWI/SNF have been
      separately implicated in derepression of the DNA damage response (DDR) genes in
      yeast cells treated with genotoxins that cause replication interference. Using
      genetic and biochemical approaches, we have tested if derepression of the DDR
      genes in budding yeast involves functional interplay between Asf1 and SWI/SNF. We
      find that Asf1 and SWI/SNF are both recruited to DDR genes under replication
      stress triggered by hydroxyurea, and have detected a soluble complex that
      contains Asf1 and the Snf2 subunit of SWI/SNF. SWI/SNF recruitment to DDR genes
      however does not require Asf1, and deletion of Snf2 does not affect Asf1
      occupancy of DDR gene promoters. A checkpoint engagement defect is sufficient to
      explain the synthetic effect of deletion of ASF1 and SNF2 on derepression of the
      DDR genes in hydroxyurea-treated cells. Collectively, our results show that the
      DDR genes fall into a class in which Asf1 and SWI/SNF independently control
      transcriptional induction.

PMID- 21738742
TI  - Spinning gland transcriptomics from two main clades of spiders (order: Araneae)-
      insights on their molecular, anatomical and behavioral evolution.
AB  - Characterized by distinctive evolutionary adaptations, spiders provide a
      comprehensive system for evolutionary and developmental studies of anatomical
      organs, including silk and venom production. Here we performed cDNA sequencing
      using massively parallel sequencers (454 GS-FLX Titanium) to generate ~80,000
      reads from the spinning gland of Actinopus spp. (infraorder: Mygalomorphae) and
      Gasteracantha cancriformis (infraorder: Araneomorphae, Orbiculariae clade).
      Actinopus spp. retains primitive characteristics on web usage and presents a
      single undifferentiated spinning gland while the orbiculariae spiders have seven
      differentiated spinning glands and complex patterns of web usage. MIRA, Celera
      Assembler and CAP3 software were used to cluster NGS reads for each spider. CAP3
      unigenes passed through a pipeline for automatic annotation, classification by
      biological function, and comparative transcriptomics. Genes related to spider
      silks were manually curated and analyzed. Although a single spidroin gene family
      was found in Actinopus spp., a vast repertoire of specialized spider silk
      proteins was encountered in orbiculariae. Astacin-like metalloproteases (meprin
      subfamily) were shown to be some of the most sampled unigenes and duplicated gene
      families in G. cancriformis since its evolutionary split from mygalomorphs. Our
      results confirm that the evolution of the molecular repertoire of silk proteins
      was accompanied by the (i) anatomical differentiation of spinning glands and (ii)
      behavioral complexification in the web usage. Finally, a phylogenetic tree was
      constructed to cluster most of the known spidroins in gene clades. This is the
      first large-scale, multi-organism transcriptome for spider spinning glands and a
      first step into a broad understanding of spider web systems biology and
      evolution.

PMID- 21738743
TI  - MicroRNA expression aberration as potential peripheral blood biomarkers for
      schizophrenia.
AB  - Since brain tissue is not readily accessible, a new focus in search of biomarkers
      for schizophrenia is blood-based expression profiling of non-protein coding genes
      such as microRNAs (miRNAs), which regulate gene expression by inhibiting the
      translation of messenger RNAs. This study aimed to identify potential miRNA
      signature for schizophrenia by comparing genome-wide miRNA expression profiles in
      patients with schizophrenia vs. healthy controls. A genome-wide miRNA expression
      profiling was performed using a Taqman array of 365 human miRNAs in the
      mononuclear leukocytes of a learning set of 30 cases and 30 controls. The
      discriminating performance of potential biomarkers was validated in an
      independent testing set of 60 cases and 30 controls. The expression levels of the
      miRNA signature were then evaluated for their correlation with the patients'
      clinical symptoms, neurocognitive performances, and neurophysiological functions.
      A seven-miRNA signature (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR
      572 and miR-652) was derived from a supervised classification with internal cross
      validation, with an area under the curve (AUC) of receiver operating
      characteristics of 93%. The putative signature was then validated in the testing
      set, with an AUC of 85%. Among these miRNAs, miR-34a was differentially expressed
      between cases and controls in both the learning (P = 0.005) and the testing set
      (P = 0.002). These miRNAs were differentially correlated with patients' negative
      symptoms, neurocognitive performance scores, and event-related potentials. The
      results indicated that the mononuclear leukocyte-based miRNA profiling is a
      feasible way to identify biomarkers for schizophrenia, and the seven-miRNA
      signature warrants further investigation.

PMID- 21738744
TI  - Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine
      induced locomotor sensitization.
AB  - BACKGROUND: The inducible cyclic adenosine monophosphate (cAMP) early repressor
      (ICER) is highly expressed in the central nervous system and functions as a
      repressor of cAMP response element-binding protein (CREB) transcription. The
      present study sought to clarify the role of ICER in the effects of
      methamphetamine (METH). METHODS AND FINDINGS: We tested METH-induced locomotor
      sensitization in wildtype mice, ICER knockout mice, and ICER I-overexpressing
      mice. Both ICER wildtype mice and knockout mice displayed increased locomotor
      activity after continuous injections of METH. However, ICER knockout mice
      displayed a tendency toward higher locomotor activity compared with wildtype
      mice, although no significant difference was observed between the two genotypes.
      Moreover, compared with wildtype mice, ICER I-overexpressing mice displayed a
      significant decrease in METH-induced locomotor sensitization. Furthermore,
      Western blot analysis and quantitative real-time reverse transcription polymerase
      chain reaction demonstrated that ICER overexpression abolished the METH-induced
      increase in CREB expression and repressed cocaine- and amphetamine-regulated
      transcript (CART) and prodynorphin (Pdyn) expression in mice. The decreased CART
      and Pdyn mRNA expression levels in vivo may underlie the inhibitory role of ICER
      in METH-induced locomotor sensitization. CONCLUSIONS: Our data suggest that ICER
      plays an inhibitory role in METH-induced locomotor sensitization.

PMID- 21738745
TI  - Multiple oxygen tension environments reveal diverse patterns of transcriptional
      regulation in primary astrocytes.
AB  - The central nervous system normally functions at O(2) levels which would be
      regarded as hypoxic by most other tissues. However, most in vitro studies of
      neurons and astrocytes are conducted under hyperoxic conditions without
      consideration of O(2)-dependent cellular adaptation. We analyzed the reactivity
      of astrocytes to 1, 4 and 9% O(2) tensions compared to the cell culture standard
      of 20% O(2), to investigate their ability to sense and translate this O(2)
      information to transcriptional activity. Variance of ambient O(2) tension for rat
      astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and
      energy-regulatory mechanisms and cytokine-related signaling. Clustering of
      transcriptional regulation patterns revealed four distinct response pattern
      groups that directionally pivoted around the 4% O(2) tension, or demonstrated
      coherent ascending/decreasing gene expression patterns in response to diverse
      oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway
      transcriptomic subsets were significantly activated with increasing hypoxia,
      whilst hemostatic and cardiovascular signaling mechanisms were attenuated with
      increasing hypoxia. Our data indicate that variant O(2) tensions induce specific
      and physiologically-focused transcript regulation patterns that may underpin
      important physiological mechanisms that connect higher neurological activity to
      astrocytic function and ambient oxygen environments. These strongly defined
      patterns demonstrate a strong bias for physiological transcript programs to pivot
      around the 4% O(2) tension, while uni-modal programs that do not, appear more
      related to pathological actions. The functional interaction of these
      transcriptional 'programs' may serve to regulate the dynamic vascular
      responsivity of the central nervous system during periods of stress or heightened
      activity.

PMID- 21738746
TI  - Crystal structures of histone and p53 methyltransferase SmyD2 reveal a
      conformational flexibility of the autoinhibitory C-terminal domain.
AB  - SmyD2 belongs to a new class of chromatin regulators that control gene expression
      in heart development and tumorigenesis. Besides methylation of histone H3 K4,
      SmyD2 can methylate non-histone targets including p53 and the retinoblastoma
      tumor suppressor. The methyltransferase activity of SmyD proteins has been
      proposed to be regulated by autoinhibition via the intra- and interdomain bending
      of the conserved C-terminal domain (CTD). However, there has been no direct
      evidence of a conformational change in the CTD. Here, we report two crystal
      structures of SmyD2 bound either to the cofactor product S-adenosylhomocysteine
      or to the inhibitor sinefungin. SmyD2 has a two-lobed structure with the active
      site located at the bottom of a deep crevice formed between the CTD and the
      catalytic domain. By extensive engagement with the methyltransferase domain, the
      CTD stabilizes the autoinhibited conformation of SmyD2 and restricts access to
      the catalytic site. Unexpectedly, despite that the two SmyD2 structures are
      highly superimposable, significant differences are observed in the first two
      helices of the CTDs: the two helices bend outwards and move away from the
      catalytic domain to generate a less closed conformation in the sinefungin-bound
      structure. Although the overall fold of the individual domains is structurally
      conserved among SmyD proteins, SmyD2 appear to be a conformational "intermediate"
      between a close form of SmyD3 and an open form of SmyD1. In addition, the
      structures reveal that the CTD is structurally similar to tetratricopeptide
      repeats (TPR), a motif through which many cochaperones bind to the heat shock
      protein Hsp90. Our results thus provide the first evidence for the intradomain
      flexibility of the TPR-like CTD, which may be important for the activation of
      SmyD proteins by Hsp90.

PMID- 21738747
TI  - Feedback enhances feedforward figure-ground segmentation by changing firing mode.
AB  - In the visual cortex, feedback projections are conjectured to be crucial in
      figure-ground segregation. However, the precise function of feedback herein is
      unclear. Here we tested a hypothetical model of reentrant feedback. We used a
      previous developed 2-layered feedforward spiking network that is able to
      segregate figure from ground and included feedback connections. Our computer
      model data show that without feedback, neurons respond with regular low-frequency
      (~9 Hz) bursting to a figure-ground stimulus. After including feedback the firing
      pattern changed into a regular (tonic) spiking pattern. In this state, we found
      an extra enhancement of figure responses and a further suppression of background
      responses resulting in a stronger figure-ground signal. Such push-pull effect was
      confirmed by comparing the figure-ground responses with the responses to a
      homogenous texture. We propose that feedback controls figure-ground segregation
      by influencing the neural firing patterns of feedforward projecting neurons.

PMID- 21738748
TI  - The gut as reservoir of antibiotic resistance: microbial diversity of
      tetracycline resistance in mother and infant.
AB  - The microbiota in the human gastrointestinal tract (GIT) is highly exposed to
      antibiotics, and may be an important reservoir of resistant strains and
      transferable resistance genes. Maternal GIT strains can be transmitted to the
      offspring, and resistances could be acquired from birth. This is a case study
      using a metagenomic approach to determine the diversity of microorganisms
      conferring tetracycline resistance (Tc(r)) in the guts of a healthy mother-infant
      pair one month after childbirth, and to investigate the potential for horizontal
      transfer and maternal transmission of Tc(r) genes. Fecal fosmid libraries were
      functionally screened for Tc(r), and further PCR-screened for specific Tc(r)
      genes. Tc(r) fosmid inserts were sequenced at both ends to establish bacterial
      diversity. Mother and infant libraries contained Tc(r), although encoded by
      different genes and organisms. Tc(r) organisms in the mother consisted mainly of
      Firmicutes and Bacteroidetes, and the main gene detected was tet(O), although
      tet(W) and tet(X) were also found. Identical Tc(r) gene sequences were present in
      different bacterial families and even phyla, which may indicate horizontal
      transfer within the maternal GIT. In the infant library, Tc(r) was present
      exclusively in streptococci carrying tet(M), tet(L) and erm(T) within a novel
      composite transposon, Tn6079. This transposon belongs to a family of broad host
      range conjugative elements, implying a potential for the joint spread of
      tetracycline and erythromycin resistance within the infant's gut. In addition,
      although not found in the infant metagenomic library, tet(O) and tet(W) could be
      detected in the uncloned DNA purified from the infant fecal sample. This is the
      first study to reveal the diversity of Tc(r) bacteria in the human gut, to detect
      a likely transmission of antibiotic resistance from mother to infant GITs and to
      indicate the possible occurrence of gene transfers among distantly related
      bacteria coinhabiting the GIT of the same individual.

PMID- 21738749
TI  - Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue
      and increases obesity development in mice.
AB  - BACKGROUND: Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect
      against high fat diet-induced obesity and inflammation in adipose tissue. Here we
      aimed to investigate if the amount of sucrose in the background diet influences
      the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue
      inflammation and glucose intolerance. METHODOLOGY/PRINCIPAL FINDINGS: We fed
      C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented
      with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source,
      mice fed diets rich in sucrose became obese whereas mice fed high protein diets
      remained lean. Inclusion of sucrose in the diet also counteracted the well-known
      anti-inflammatory effect of fish oil in adipose tissue, but did not impair the
      ability of fish oil to prevent accumulation of fat in the liver. Calculation of
      HOMA-IR indicated that mice fed high levels of proteins remained insulin
      sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose
      irrespectively of the fat source. We show that a high fat diet decreased glucose
      tolerance in the mice independently of both obesity and dietary levels of n-3
      PUFAs and sucrose. Of note, increasing the protein?sucrose ratio in high fat
      diets decreased energy efficiency irrespective of fat source. This was
      accompanied by increased expression of Ppargc1a (peroxisome proliferator
      activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in
      the fed state. CONCLUSIONS/SIGNIFICANCE: The background diet influence the
      ability of n-3 PUFAs to protect against development of obesity, glucose
      intolerance and adipose tissue inflammation. High levels of dietary sucrose
      counteract the anti-inflammatory effect of fish oil in adipose tissue and
      increases obesity development in mice.

PMID- 21738750
TI  - Transcriptional priming of Salmonella Pathogenicity Island-2 precedes cellular
      invasion.
AB  - Invasive salmonellosis caused by Salmonella enterica involves an enteric stage of
      infection where the bacteria colonize mucosal epithelial cells, followed by
      systemic infection with intracellular replication in immune cells. The type III
      secretion system encoded in Salmonella Pathogenicity Island (SPI)-2 is essential
      for intracellular replication and the regulators governing high-level expression
      of SPI-2 genes within the macrophage phagosome and in inducing media thought to
      mimic this environment have been well characterized. However, low-level
      expression of SPI-2 genes is detectable in media thought to mimic the
      extracellular environment suggesting that additional regulatory pathways are
      involved in SPI-2 gene expression prior to cellular invasion. The regulators
      involved in this activity are not known and the extracellular transcriptional
      activity of the entire SPI-2 island in vivo has not been studied. We show that
      low-level, SsrB-independent promoter activity for the ssrA-ssrB two-component
      regulatory system and the ssaG structural operon encoded in SPI-2 is dependent on
      transcriptional input by OmpR and Fis under non-inducing conditions. Monitoring
      the activity of all SPI-2 promoters in real-time following oral infection of mice
      revealed invasion-independent transcriptional activity of the SPI2 T3SS in the
      lumen of the gut, which we suggest is a priming activity with functional
      relevance for the subsequent intracellular host-pathogen interaction.

PMID- 21738751
TI  - Millisecond-timescale local network coding in the rat primary somatosensory
      cortex.
AB  - Correlation among neocortical neurons is thought to play an indispensable role in
      mediating sensory processing of external stimuli. The role of temporal precision
      in this correlation has been hypothesized to enhance information flow along
      sensory pathways. Its role in mediating the integration of information at the
      output of these pathways, however, remains poorly understood. Here, we examined
      spike timing correlation between simultaneously recorded layer V neurons within
      and across columns of the primary somatosensory cortex of anesthetized rats
      during unilateral whisker stimulation. We used bayesian statistics and
      information theory to quantify the causal influence between the recorded cells
      with millisecond precision. For each stimulated whisker, we inferred stable,
      whisker-specific, dynamic bayesian networks over many repeated trials, with
      network similarity of 83.3+/-6% within whisker, compared to only 50.3+/-18%
      across whiskers. These networks further provided information about whisker
      identity that was approximately 6 times higher than what was provided by the
      latency to first spike and 13 times higher than what was provided by the spike
      count of individual neurons examined separately. Furthermore, prediction of
      individual neurons' precise firing conditioned on knowledge of putative pre
      synaptic cell firing was 3 times higher than predictions conditioned on stimulus
      onset alone. Taken together, these results suggest the presence of a temporally
      precise network coding mechanism that integrates information across neighboring
      columns within layer V about vibrissa position and whisking kinetics to mediate
      whisker movement by motor areas innervated by layer V.

PMID- 21738752
TI  - Minor HIV-1 variants with the K103N resistance mutation during intermittent
      efavirenz-containing antiretroviral therapy and virological failure.
AB  - The impact of minor drug-resistant variants of the type 1 immunodeficiency virus
      (HIV-1) on the failure of antiretroviral therapy remains unclear. We have
      evaluated the importance of detecting minor populations of viruses resistant to
      non-nucleoside reverse-transcriptase inhibitors (NNRTI) during intermittent
      antiretroviral therapy, a high-risk context for the emergence of drug-resistant
      HIV-1. We carried out a longitudinal study on plasma samples taken from 21
      patients given efavirenz and enrolled in the intermittent arm of the ANRS 106
      trial. Allele-specific real-time PCR was used to detect and quantify minor K103N
      mutants during off-therapy periods. The concordance with ultra-deep
      pyrosequencing was assessed for 11 patients. The pharmacokinetics of efavirenz
      was assayed to determine whether its variability could influence the emergence of
      K103N mutants. Allele-specific real-time PCR detected K103N mutants in 15 of the
      19 analyzable patients at the end of an off-therapy period while direct
      sequencing detected mutants in only 6 patients. The frequency of K103N mutants
      was <0.1% in 7 patients by allele-specific real-time PCR without further
      selection, and >0.1% in 8. It was 0.1%-10% in 6 of these 8 patients. The mutated
      virus populations of 4 of these 6 patients underwent further selection and
      treatment failed for 2 of them. The K103N mutant frequency was >10% in the
      remaining 2, treatment failed for one. The copy numbers of K103N variants
      quantified by allele-specific real-time PCR and ultra-deep pyrosequencing agreed
      closely (rho = 0.89 P<0.0001). The half-life of efavirenz was higher (50.5 hours)
      in the 8 patients in whom K103N emerged (>0.1%) than in the 11 patients in whom
      it did not (32 hours) (P = 0.04). Thus ultrasensitive methods could prove more
      useful than direct sequencing for predicting treatment failure in some patients.
      However the presence of minor NNRTI-resistant viruses need not always result in
      virological escape. TRIAL REGISTRATION: ClinicalTrials.gov NCT00122551.

PMID- 21738753
TI  - Albumin-like protein is the major protein constituent of luminal fluid in the
      human endolymphatic sac.
AB  - The endolymphatic sac (ES) is an inner ear organ that is connected to the cochleo
      vestibular system through the endolymphatic duct. The luminal fluid of the ES
      contains a much higher concentration of proteins than any other compartment of
      the inner ear. This high protein concentration likely contributes to inner ear
      fluid volume regulation by creating an osmotic gradient between the ES lumen and
      the interstitial fluid. We characterized the protein profile of the ES luminal
      fluid of patients (n = 11) with enlarged vestibular aqueducts (EVA) by
      proteomics. In addition, we investigated differences in the protein profiles
      between patients with recent hearing deterioration and patients without hearing
      deterioration. The mean total protein concentration of the luminal fluid was
      554.7+/-94.6 mg/dl. A total of 58 out of 517 spots detected by 2-DE were analyzed
      by MALDI-TOF MS. The protein profile of the luminal fluid was different from the
      profile of plasma. Proteins identified from 29 of the spots were also present in
      the MARC-filtered human plasma; however, the proteins identified from the other
      25 spots were not detected in the MARC-filtered human plasma. The most abundant
      protein in the luminal fluid was albumin-like proteins, but most of them were not
      detected in MARC-filtered human plasma. The concentration of albumin-like
      proteins was higher in samples from patients without recent hearing deterioration
      than in patients with recent hearing deterioration. Consequently, the protein of
      ES luminal fluid is likely to be originated from both the plasma and the inner
      ear and considering that inner ear fluid volumes increase abnormally in patients
      with EVA following recent hearing deterioration, it is tempting to speculate that
      albumin-like proteins may be involved in the regulation of inner ear fluid volume
      through creation of an osmotic gradient during pathological conditions such as
      endolymphatic hydrops.

PMID- 21738754
TI  - High DNA methylation pattern intratumoral diversity implies weak selection in
      many human colorectal cancers.
AB  - BACKGROUND: It is possible to infer the past of populations by comparing genomes
      between individuals. In general, older populations have more genomic diversity
      than younger populations. The force of selection can also be inferred from
      population diversity. If selection is strong and frequently eliminates less fit
      variants, diversity will be limited because new, initially homogeneous
      populations constantly emerge. METHODOLOGY AND RESULTS: Here we translate a
      population genetics approach to human somatic cancer cell populations by
      measuring genomic diversity within and between small colorectal cancer (CRC)
      glands. Control tissue culture and xenograft experiments demonstrate that the
      population diversity of certain passenger DNA methylation patterns is reduced
      after cloning but subsequently increases with time. When measured in CRC gland
      populations, passenger methylation diversity from different parts of nine CRCs
      was relatively high and uniform, consistent with older, stable lineages rather
      than mixtures of younger homogeneous populations arising from frequent cycles of
      selection. The diversity of six metastases was also high, suggesting
      dissemination early after transformation. Diversity was lower in DNA mismatch
      repair deficient CRC glands, possibly suggesting more selection and the
      elimination of less fit variants when mutation rates are elevated.
      CONCLUSION/SIGNIFICANCE: The many hitchhiking passenger variants observed in
      primary and metastatic CRC cell populations are consistent with relatively old
      populations, suggesting that clonal evolution leading to selective sweeps may be
      rare after transformation. Selection in human cancers appears to be a weaker than
      presumed force after transformation, consistent with the observed rarity of
      driver mutations in cancer genomes. Phenotypic plasticity rather than the
      stepwise acquisition of new driver mutations may better account for the many
      different phenotypes within human tumors.

PMID- 21738755
TI  - Broad antiviral activity of carbohydrate-binding agents against the four
      serotypes of dengue virus in monocyte-derived dendritic cells.
AB  - BACKGROUND: Dendritic cells (DC), present in the skin, are the first target cells
      of dengue virus (DENV). Dendritic cell-specific intercellular adhesion molecule 3
      grabbing non-integrin (DC-SIGN) is present on DC and recognizes N-glycosylation
      sites on the E-glycoprotein of DENV. Thus, the DC-SIGN/E-glycoprotein interaction
      can be considered as an important target for inhibitors of viral replication. We
      evaluated various carbohydrate-binding agents (CBAs) against all four described
      serotypes of DENV replication in Raji/DC-SIGN(+) cells and in monocyte-derived DC
      (MDDC). METHODOLOGY/PRINCIPAL FINDINGS: A dose-dependent anti-DENV activity of
      the CBAs Hippeastrum hybrid (HHA), Galanthus nivalis (GNA) and Urtica dioica
      (UDA), but not actinohivin (AH) was observed against all four DENV serotypes as
      analyzed by flow cytometry making use of anti-DENV antibodies. Remarkably, the
      potency of the CBAs against DENV in MDDC cultures was significantly higher (up to
      100-fold) than in Raji/DC-SIGN(+) cells. Pradimicin-S (PRM-S), a small-size non
      peptidic CBA, exerted antiviral activity in MDDC but not in Raji/DC-SIGN(+)
      cells. The CBAs act at an early step of DENV infection as they bind to the viral
      envelope of DENV and subsequently prevent virus attachment. Only weak antiviral
      activity of the CBAs was detected when administered after the virus attachment
      step. The CBAs were also able to completely prevent the cellular activation and
      differentiation process of MDDC induced upon DENV infection.
      CONCLUSIONS/SIGNIFICANCE: The CBAs exerted broad spectrum antiviral activity
      against the four DENV serotypes, laboratory-adapted viruses and low passage
      clinical isolates, evaluated in Raji/DC-SIGN(+) cells and in primary MDDC.

PMID- 21738756
TI  - The Rubber Hand Illusion: feeling of ownership and proprioceptive drift do not go
      hand in hand.
AB  - In the Rubber Hand Illusion, the feeling of ownership of a rubber hand displaced
      from a participant's real occluded hand is evoked by synchronously stroking both
      hands with paintbrushes. A change of perceived finger location towards the rubber
      hand (proprioceptive drift) has been reported to correlate with this illusion. To
      measure the time course of proprioceptive drift during the Rubber Hand Illusion,
      we regularly interrupted stroking (performed by robot arms) to measure perceived
      finger location. Measurements were made by projecting a probe dot into the field
      of view (using a semi-transparent mirror) and asking participants if the dot is
      to the left or to the right of their invisible hand (Experiment 1) or to adjust
      the position of the dot to that of their invisible hand (Experiment 2). We varied
      both the measurement frequency (every 10 s, 40 s, 120 s) and the mode of stroking
      (synchronous, asynchronous, just vision). Surprisingly, with frequent
      measurements, proprioceptive drift occurs not only in the synchronous stroking
      condition but also in the two control conditions (asynchronous stroking, just
      vision). Proprioceptive drift in the synchronous stroking condition is never
      higher than in the just vision condition. Only continuous exposure to
      asynchronous stroking prevents proprioceptive drift and thus replicates the
      differences in drift reported in the literature. By contrast, complementary
      subjective ratings (questionnaire) show that the feeling of ownership requires
      synchronous stroking and is not present in the asynchronous stroking condition.
      Thus, subjective ratings and drift are dissociated. We conclude that different
      mechanisms of multisensory integration are responsible for proprioceptive drift
      and the feeling of ownership. Proprioceptive drift relies on visuoproprioceptive
      integration alone, a process that is inhibited by asynchronous stroking, the most
      common control condition in Rubber Hand Illusion experiments. This dissociation
      implies that conclusions about feelings of ownership cannot be drawn from
      measuring proprioceptive drift alone.

PMID- 21738757
TI  - Amitriptyline-mediated cognitive enhancement in aged 3*Tg Alzheimer's disease
      mice is associated with neurogenesis and neurotrophic activity.
AB  - Approximately 35 million people worldwide suffer from Alzheimer's disease (AD).
      Existing therapeutics, while moderately effective, are currently unable to stem
      the widespread rise in AD prevalence. AD is associated with an increase in
      amyloid beta (Abeta) oligomers and hyperphosphorylated tau, along with cognitive
      impairment and neurodegeneration. Several antidepressants have shown promise in
      improving cognition and alleviating oxidative stress in AD but have failed as
      long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic
      antidepressant, was administered orally to aged and cognitively impaired
      transgenic AD mice (3*TgAD). After amitriptyline treatment, cognitive behavior
      testing demonstrated that there was a significant improvement in both long- and
      short-term memory retention. Amitriptyline treatment also caused a significant
      potentiation of non-toxic Abeta monomer with a concomitant decrease in cytotoxic
      dimer Abeta load, compared to vehicle-treated 3*TgAD controls. In addition,
      amitriptyline administration caused a significant increase in dentate gyrus
      neurogenesis as well as increases in expression of neurosynaptic marker proteins.
      Amitriptyline treatment resulted in increases in hippocampal brain-derived
      neurotrophic factor protein as well as increased tyrosine phosphorylation of its
      cognate receptor (TrkB). These results indicate that amitriptyline has
      significant beneficial actions in aged and damaged AD brains and that it shows
      promise as a tolerable novel therapeutic for the treatment of AD.

PMID- 21738758
TI  - S100B protein, brain-derived neurotrophic factor, and glial cell line-derived
      neurotrophic factor in human milk.
AB  - BACKGROUND: Human milk contains a wide variety of nutrients that contribute to
      the fulfillment of its functions, which include the regulation of newborn
      development. However, few studies have investigated the concentrations of S100B
      protein, brain-derived neurotrophic factor (BDNF), and glial cell line-derived
      neurotrophic factor (GDNF) in human milk. The associations of the concentrations
      of S100B protein, BDNF, and GDNF with maternal factors are not well explored.
      METHODOLOGY/PRINCIPAL FINDINGS: To investigate the concentrations of S100B
      protein, BDNF, and GDNF in human milk and characterize the maternal factors
      associated with their levels in human milk, human milk samples were collected at
      days 3, 10, 30, and 90 after parturition. Levels of S100B protein, BDNF, and
      GDNF, and their mRNAs in the samples were detected. Then, these concentrations
      were compared with lactation and other maternal factors. S100B protein levels in
      human milk samples collected at 3, 10, 30, and 90 d after parturition were
      1249.79+/-398.10, 1345.05+/-539.16, 1481.83+/-573.30, and 1414.39+/-621.31 ng/L,
      respectively. On the other hand, the BDNF concentrations in human milk samples
      were 10.99+/-4.55, 13.01+/-5.88, 13.35+/-6.43, and 2.83+/-5.47 ug/L, while those
      of GDNF were 10.90+/-1.65, 11.38+/-1., 11.29+/-3.10, and 11.40+/-2.21 g/L for the
      same time periods. Maternal post-pregnancy body mass index was positively
      associated with S100B levels in human milk (r = 0.335, P = 0.030<0.05). In
      addition, there was a significant correlation between the levels of S100B protein
      and BDNF (z = 2.09, P = 0.037<0.05). Delivery modes were negatively associated
      with the concentration of GDNF in human milk. CONCLUSIONS: S100B protein, BDNF,
      and GDNF are present in all samples of human milk, and they may be responsible
      for the long term effects of breast feeding.

PMID- 21738759
TI  - Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6
      D13S1854).
AB  - Mutations in the GJB2 gene, which encodes connexin 26, are a frequent cause of
      congenital non-syndromic sensorineural hearing loss. Two large deletions,
      del(GJB6-D13S1830) and del(GJB6-D13S1854), which truncate GJB6 (connexin 30),
      cause hearing loss in individuals homozygous, or compound heterozygous for these
      deletions or one such deletion and a mutation in GJB2. Recently, we have
      demonstrated that the del(GJB6-D13S1830) deletion contributes to hearing loss due
      to an allele-specific lack of GJB2 mRNA expression and not as a result of digenic
      inheritance, as was postulated earlier. In the current study we investigated the
      smaller del(GJB6-D13S1854) deletion, which disrupts the expression of GJB2 at the
      transcriptional level in a manner similar to the more common del(GJB6-D13S1830)
      deletion. Interestingly, in the presence of this deletion, GJB2 expression
      remains minimally but reproducibly present. The relative allele-specific
      expression of GJB2 was assessed by reverse-transcriptase PCR and restriction
      digestions in three probands who were compound heterozygous for a GJB2 mutation
      and del(GJB6-D13S1854). Each individual carried a different sequence variant in
      GJB2. All three individuals expressed the mutated GJB2 allele in trans with
      del(GJB6-D13S1854), but expression of the GJB2 allele in cis with the deletion
      was almost absent. Our study clearly corroborates the hypothesis that the
      del(GJB6-D13S1854), similar to the larger and more common del(GJB6-D13S1830),
      removes (a) putative cis-regulatory element(s) upstream of GJB6 and narrows down
      the region of location.

PMID- 21738760
TI  - Histology of the pharyngeal constrictor muscle in 22q11.2 deletion syndrome and
      non-syndromic children with velopharyngeal insufficiency.
AB  - Plastic surgeons aim to correct velopharyngeal insufficiency manifest by
      hypernasal speech with a velopharyngoplasty. The functional outcome has been
      reported to be worse in patients with 22q11.2 deletion syndrome than in patients
      without the syndrome. A possible explanation is the hypotonia that is often
      present as part of the syndrome. To confirm a myogenic component of the etiology
      of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome,
      specimens of the pharyngeal constrictor muscle were taken from children with and
      without the syndrome. Histologic properties were compared between the groups.
      Specimens from the two groups did not differ regarding the presence of increased
      perimysial or endomysial space, fiber grouping by size or type, internalized
      nuclei, the percentage type I fibers, or the diameters of type I and type II
      fibers. In conclusion, a myogenic component of the etiology of velopharyngeal
      insufficiency in children with 22q11.2 deletion syndrome could not be confirmed.

PMID- 21738761
TI  - Difference in virulence of Mycobacterium avium isolates sharing indistinguishable
      DNA fingerprint determined in murine model of lung infection.
AB  - BACKGROUND: Opportunistic Mycobacterium avium typically causes disease in
      immunocompromised patients and in some groups of apparently healthy individuals.
      The high virulence of some bacterial lineages increases the disease risk. High
      resolution molecular genotyping studies of M. avium clinical isolates
      demonstrated that some genotype patterns were more prevalent than others,
      suggesting that close genetic relatedness of these successful isolates sharing a
      similar genotype could determine similar biological properties associated with
      high virulence. METHODS AND FINDINGS: In this study, we aimed to compare the
      virulence and pathogenic properties of two epidemiologically unrelated M. avium
      isolates sharing an indistinguishable DNA fingerprint in a well-characterized
      model of pulmonary infection in mice, resistant or susceptible to mycobacteria.
      The mice, C57BL/6 wild- type or IFN-gamma gene disrupted (GKO), respectively,
      were intratracheally infected with two isolates, H27 (human blood isolate) and
      P104 (pig lymph node isolate), and the lungs were examined for bacterial loads,
      histopathology and cytokine gene expression. The obtained data demonstrated
      significant differences in the virulence properties of these strains. Although
      the H27 strain grew significantly faster than P104 in the early stage of
      infection, this bacterium induced protective immunity that started to reduce
      bacterial numbers in the wild-type mice, whereas the P104 strain established a
      chronic infection. In the GKO mice, both strains were capable of causing a
      chronic infection, associated with higher bacterial burdens and severe lung
      pathology, in a similar manner. CONCLUSIONS/SIGNIFICANCE: The results
      demonstrated that the studied isolates differed in the pathogenic properties
      although were indistinguishable by actually widely used genotyping techniques
      demonstrating that the genotype similarity does not predict similarity in
      virulence of M. avium isolates.

PMID- 21738762
TI  - Regulation of Mycobacterium-specific mononuclear cell responses by 25
      hydroxyvitamin D3.
AB  - The active vitamin D metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)),
      has been shown to be an important regulator of innate and adaptive immune
      function. In addition, synthesis of 1,25(OH)(2)D(3) from 25-hydroxyvitamin D(3)
      (25(OH)D(3)) by the enzyme 1alpha-hydroxylase in monocytes upon activation by TLR
      signaling has been found to regulate innate immune responses of monocytes in an
      intracrine fashion. In this study we wanted to determine what cells expressed
      1alpha-hydroxylase in stimulated peripheral blood mononuclear cell (PBMC)
      cultures and if conversion of 25(OH)D(3) to 1,25(OH)(2)D(3) in PBMC cultures
      regulated antigen-specific immune responses. Initially, we found that stimulation
      of PBMCs from animals vaccinated with Mycobacterium bovis (M. bovis) BCG with
      purified protein derivative of M. bovis (M. bovis PPD) induced 1alpha-hydroxylase
      gene expression and that treatment with a physiological concentration of
      25(OH)D(3) down-regulated IFN-gamma and IL-17F gene expression. Next, we
      stimulated PBMCs from M. bovis BCG-vaccinated and non-vaccinated cattle with M.
      bovis PPD and sorted them by FACS according to surface markers for
      monocytes/macrophages (CD14), B cells (IgM), and T cells (CD3). Sorting the PBMCs
      revealed that 1alpha-hydroxylase expression was induced in the monocytes and B
      cells, but not in the T cells. Furthermore, treatment of stimulated PBMCs with
      25(OH)D(3) down-regulated antigen-specific IFN-gamma and IL-17F responses in the
      T cells, even though 1alpha-hydroxylase expression was not induced in the T
      cells. Based on evidence of no T cell 1alpha-hydroxylase we hypothesize that
      activated monocytes and B cells synthesize 1,25(OH)(2)D(3) and that
      1,25(OH)(2)D(3) down-regulates antigen-specific expression of IFN-gamma and IL
      17F in T cells in a paracrine fashion.

PMID- 21738763
TI  - The spread of fecally transmitted parasites in socially-structured populations.
AB  - Mammals are infected by a wide array of gastrointestinal parasites, including
      parasites that also infect humans and domesticated animals. Many of these
      parasites are acquired through contact with infectious stages present in soil,
      feces or vegetation, suggesting that ranging behavior will have a major impact on
      their spread. We developed an individual-based spatial simulation model to
      investigate how range use intensity, home range overlap, and defecation rate
      impact the spread of fecally transmitted parasites in a population composed of
      social groups (i.e., a socially structured population). We also investigated the
      effects of epidemiological parameters involving host and parasite mortality
      rates, transmissibility, disease-related mortality, and group size. The model was
      spatially explicit and involved the spillover of a gastrointestinal parasite from
      a reservoir population along the edge of a simulated reserve, which was designed
      to mimic the introduction pathogens into protected areas. Animals ranged randomly
      within a "core" area, with biased movement toward the range center when outside
      the core. We systematically varied model parameters using a Latin hypercube
      sampling design. Analyses of simulation output revealed a strong positive
      association between range use intensity and the prevalence of infection.
      Moreover, the effects of range use intensity were similar in magnitude to effects
      of group size, mortality rates, and the per-contact probability of transmission.
      Defecation rate covaried positively with gastrointestinal parasite prevalence.
      Greater home range overlap had no positive effects on prevalence, with a smaller
      core resulting in less range overlap yet more intensive use of the home range and
      higher prevalence. Collectively, our results reveal that parasites with fecal
      oral transmission spread effectively in socially structured populations. Future
      application should focus on parameterizing the model with empirically derived
      ranging behavior for different species or populations and data on transmission
      characteristics of different infectious organisms.

PMID- 21738764
TI  - Mitochondrial localized STAT3 is involved in NGF induced neurite outgrowth.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) plays
      critical roles in neural development and is increasingly recognized as a major
      mediator of injury response in the nervous system. Cytokines and growth factors
      are known to phosphorylate STAT3 at tyrosine(705) with or without the concomitant
      phosphorylation at serine(727), resulting in the nuclear localization of STAT3
      and subsequent transcriptional activation of genes. Recent evidence suggests that
      STAT3 may control cell function via alternative mechanisms independent of its
      transcriptional activity. Currently, the involvement of STAT3 mono-phosphorylated
      at residue serine(727) (P-Ser-STAT3) in neurite outgrowth and the underlying
      mechanism is largely unknown. PRINCIPAL FINDINGS: In this study, we investigated
      the role of nerve growth factor (NGF) induced P-Ser-STAT3 in mediating neurite
      outgrowth. NGF induced the phosphorylation of residue serine(727) but not
      tyrosine(705) of STAT3 in PC12 and primary cortical neuronal cells. In PC12
      cells, serine but not tyrosine dominant negative mutant of STAT3 was found to
      impair NGF induced neurite outgrowth. Unexpectedly, NGF induced P-Ser-STAT3 was
      localized to the mitochondria but not in the nucleus. Mitochondrial STAT3 was
      further found to be intimately involved in NGF induced neurite outgrowth and the
      production of reactive oxygen species (ROS). CONCLUSION: Taken together, the
      findings herein demonstrated a hitherto unrecognized novel transcription
      independent mechanism whereby the mitochondria localized P-Ser-STAT3 is involved
      in NGF induced neurite outgrowth.

PMID- 21738765
TI  - Enzymes are enriched in bacterial essential genes.
AB  - Essential genes, those indispensable for the survival of an organism, play a key
      role in the emerging field, synthetic biology. Characterization of functions
      encoded by essential genes not only has important practical implications, such as
      in identifying antibiotic drug targets, but can also enhance our understanding of
      basic biology, such as functions needed to support cellular life. Enzymes are
      critical for almost all cellular activities. However, essential genes have not
      been systematically examined from the aspect of enzymes and the chemical
      reactions that they catalyze. Here, by comprehensively analyzing essential genes
      in 14 bacterial genomes in which large-scale gene essentiality screens have been
      performed, we found that enzymes are enriched in essential genes. Essential
      enzymes have overrepresented ligases (especially those forming carbon-oxygen
      bonds and carbon-nitrogen bonds), nucleotidyltransferases and
      phosphotransferases, while have underrepresented oxidoreductases. Furthermore,
      essential enzymes tend to associate with more gene ontology domains. These
      results, from the aspect of chemical reactions, provide further insights into the
      understanding of functions needed to support natural cellular life, as well as
      synthetic cells, and provide additional parameters that can be integrated into
      gene essentiality prediction algorithms.

PMID- 21738766
TI  - Proton magnetic resonance spectroscopy in 22q11 deletion syndrome.
AB  - OBJECTIVE: People with velo-cardio-facial syndrome or 22q11 deletion syndrome
      (22q11DS) have behavioral, cognitive and psychiatric problems. Approximately 30%
      of affected individuals develop schizophrenia-like psychosis. Glutamate
      dysfunction is thought to play a crucial role in schizophrenia. However, it is
      unknown if and how the glutamate system is altered in 22q11DS. People with
      22q11DS are vulnerable for haploinsufficiency of PRODH, a gene that codes for an
      enzyme converting proline into glutamate. Therefore, it can be hypothesized that
      glutamatergic abnormalities may be present in 22q11DS. METHOD: We employed proton
      magnetic resonance spectroscopy ((1)H-MRS) to quantify glutamate and other
      neurometabolites in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of
      22 adults with 22q11DS (22q11DS SCZ+) and without (22q11DS SCZ-) schizophrenia
      and 23 age-matched healthy controls. Also, plasma proline levels were determined
      in the 22q11DS group. RESULTS: We found significantly increased concentrations of
      glutamate and myo-inositol in the hippocampal region of 22q11DS SCZ+ compared to
      22q11DS SCZ-. There were no significant differences in levels of plasma proline
      between 22q11DS SCZ+ and 22q11DS SCZ-. There was no relationship between plasma
      proline and cerebral glutamate in 22q11DS. CONCLUSION: This is the first in
      vivo(1)H-MRS study in 22q11DS. Our results suggest vulnerability of the
      hippocampus in the psychopathology of 22q11DS SCZ+. Altered hippocampal glutamate
      and myo-inositol metabolism may partially explain the psychotic symptoms and
      cognitive impairments seen in this group of patients.

PMID- 21738767
TI  - Semaphorin-1a is required for Aedes aegypti embryonic nerve cord development.
AB  - Although mosquito genome projects have uncovered orthologues of many known
      developmental regulatory genes, extremely little is known about mosquito
      development. In this study, the role of semaphorin-1a (sema1a) was investigated
      during vector mosquito embryonic ventral nerve cord development. Expression of
      sema1a and the plexin A (plexA) receptor are detected in the embryonic ventral
      nerve cords of Aedes aegypti (dengue vector) and Anopheles gambiae (malaria
      vector), suggesting that Sema1a signaling may regulate mosquito nervous system
      development. Analysis of sema1a function was investigated through siRNA-mediated
      knockdown in A. aegypti embryos. Knockdown of sema1a during A. aegypti
      development results in a number of nerve cord phenotypes, including thinning,
      breakage, and occasional fusion of the longitudinal connectives, thin or absent
      commissures, and general distortion of the nerve cord. Although analysis of
      Drosophila melanogaster sema1a loss-of-function mutants uncovered many similar
      phenotypes, aspects of the longitudinal phenotypes differed between D.
      melanogaster and A. aegypti. The results of this investigation suggest that
      Sema1a is required for development of the insect ventral nerve cord, but that the
      developmental roles of this guidance molecule have diverged in dipteran insects.

PMID- 21738768
TI  - A polymorphism in the splice donor site of ZNF419 results in the novel renal cell
      carcinoma-associated minor histocompatibility antigen ZAPHIR.
AB  - Nonmyeloablative allogeneic stem cell transplantation (SCT) can induce remission
      in patients with renal cell carcinoma (RCC), but this graft-versus-tumor (GVT)
      effect is often accompanied by graft-versus-host disease (GVHD). Here, we
      evaluated minor histocompatibility antigen (MiHA)-specific T cell responses in
      two patients with metastatic RCC who were treated with reduced-intensity
      conditioning SCT followed by donor lymphocyte infusion (DLI). One patient had
      stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after
      DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second
      patient experienced partial regression of lung metastases from whom we isolated a
      MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole
      genome association scanning revealed that this CTL recognizes a novel HLA-B7
      restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice
      donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR
      specific CD8+ T cells in peripheral blood occurred in the absence of GVHD.
      Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the
      involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity.
      These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive
      target for specific immunotherapy after allogeneic SCT.

PMID- 21738769
TI  - Analysis of the CD1 antigen presenting system in humanized SCID mice.
AB  - CD1 molecules are glycoproteins that present lipids and glycolipids for
      recognition by T cells. CD1-dependent immune activation has been implicated in a
      wide range of immune responses, however, our understanding of the role of this
      pathway in human disease remains limited because of species differences between
      humans and other mammals: whereas humans express five different CD1 gene products
      (CD1a, CD1b, CD1c, CD1d, and CD1e), muroid rodents express only one CD1 isoform
      (CD1d). Here we report that immune deficient mice engrafted with human fetal
      thymus, liver, and CD34(+) hematopoietic stem cells develop a functional human
      CD1 compartment. CD1a, b, c, and d isoforms were highly expressed by human
      thymocytes, and CD1a(+) cells with a dendritic morphology were present in the
      thymic medulla. CD1(+) cells were also detected in spleen, liver, and lungs. APCs
      from spleen and liver were capable of presenting bacterial glycolipids to human
      CD1-restricted T cells. ELISpot analyses of splenocytes demonstrated the presence
      of CD1-reactive IFN-gamma producing cells. CD1d tetramer staining directly
      identified human iNKT cells in spleen and liver samples from engrafted mice, and
      injection of the glycolipid antigen alpha-GalCer resulted in rapid elevation of
      human IFN-gamma and IL-4 levels in the blood indicating that the human iNKT cells
      are biologically active in vivo. Together, these results demonstrate that the
      human CD1 system is present and functionally competent in this humanized mouse
      model. Thus, this system provides a new opportunity to study the role of CD1
      related immune activation in infections to human-specific pathogens.

PMID- 21738770
TI  - Identification of novel linear megaplasmids carrying a beta-lactamase gene in
      neurotoxigenic Clostridium butyricum type E strains.
AB  - Since the first isolation of type E botulinum toxin-producing Clostridium
      butyricum from two infant botulism cases in Italy in 1984, this peculiar
      microorganism has been implicated in different forms of botulism worldwide. By
      applying particular pulsed-field gel electrophoresis run conditions, we were able
      to show for the first time that ten neurotoxigenic C. butyricum type E strains
      originated from Italy and China have linear megaplasmids in their genomes. At
      least four different megaplasmid sizes were identified among the ten
      neurotoxigenic C. butyricum type E strains. Each isolate displayed a single sized
      megaplasmid that was shown to possess a linear structure by ATP-dependent
      exonuclease digestion. Some of the neurotoxigenic C. butyricum type E strains
      possessed additional smaller circular plasmids. In order to investigate the
      genetic content of the newly identified megaplasmids, selected gene probes were
      designed and used in Southern hybridization experiments. Our results revealed
      that the type E botulinum neurotoxin gene was chromosome-located in all
      neurotoxigenic C. butyricum type E strains. Similar results were obtained with
      the 16S rRNA, the tetracycline tet(P) and the lincomycin resistance protein lmrB
      gene probes. A specific mobA gene probe only hybridized to the smaller plasmids
      of the Italian C. butyricum type E strains. Of note, a beta-lactamase gene probe
      hybridized to the megaplasmids of eight neurotoxigenic C. butyricum type E
      strains, of which seven from clinical sources and the remaining one from a food
      implicated in foodborne botulism, whereas this beta-lactam antibiotic resistance
      gene was absent form the megaplasmids of the two soil strains examined. The
      widespread occurrence among C. butyricum type E strains associated to human
      disease of linear megaplasmids harboring an antibiotic resistance gene strongly
      suggests that the megaplasmids could have played an important role in the
      emergence of C. butyricum type E as a human pathogen.

PMID- 21738771
TI  - Morphine induces expression of platelet-derived growth factor in human brain
      microvascular endothelial cells: implication for vascular permeability.
AB  - Despite the advent of antiretroviral therapy, complications of HIV-1 infection
      with concurrent drug abuse are an emerging problem. Morphine, often abused by HIV
      infected patients, is known to accelerate neuroinflammation associated with HIV-1
      infection. Detailed molecular mechanisms of morphine action however, remain
      poorly understood. Platelet-derived growth factor (PDGF) has been implicated in a
      number of pathological conditions, primarily due to its potent mitogenic and
      permeability effects. Whether morphine exposure results in enhanced vascular
      permeability in brain endothelial cells, likely via induction of PDGF, remains to
      be established. In the present study, we demonstrated morphine-mediated induction
      of PDGF-BB in human brain microvascular endothelial cells, an effect that was
      abrogated by the opioid receptor antagonist-naltrexone. Pharmacological blockade
      (cell signaling) and loss-of-function (Egr-1) approaches demonstrated the role of
      mitogen-activated protein kinases (MAPKs), PI3K/Akt and the downstream
      transcription factor Egr-1 respectively, in morphine-mediated induction of PDGF
      BB. Functional significance of increased PDGF-BB manifested as increased breach
      of the endothelial barrier as evidenced by decreased expression of the tight
      junction protein ZO-1 in an in vitro model system. Understanding the regulation
      of PDGF expression may provide insights into the development of potential
      therapeutic targets for intervention of morphine-mediated neuroinflammation.

PMID- 21738772
TI  - Global patterns of guild composition and functional diversity of spiders.
AB  - The objectives of this work are: (1) to define spider guilds for all extant
      families worldwide; (2) test if guilds defined at family level are good
      surrogates of species guilds; (3) compare the taxonomic and guild composition of
      spider assemblages from different parts of the world; (4) compare the taxonomic
      and functional diversity of spider assemblages and; (5) relate functional
      diversity with habitat structure. Data on foraging strategy, prey range, vertical
      stratification and circadian activity was collected for 108 families. Spider
      guilds were defined by hierarchical clustering. We searched for inconsistencies
      between family guild placement and the known guild of each species. Richness and
      abundance per guild before and after correcting guild placement were compared, as
      were the proportions of each guild and family between all possible pairs of
      sites. Functional diversity per site was calculated based on hierarchical
      clustering. Eight guilds were discriminated: (1) sensing, (2) sheet, (3) space,
      and (4) orb web weavers; (5) specialists; (6) ambush, (7) ground, and (8) other
      hunters. Sixteen percent of the species richness corresponding to 11% of all
      captured individuals was incorrectly attributed to a guild by family surrogacy;
      however, the correlation of uncorrected vs. corrected guilds was invariably high.
      The correlation of guild richness or abundances was generally higher than the
      correlation of family richness or abundances. Functional diversity was not always
      higher in the tropics than in temperate regions. Families may potentially serve
      as ecological surrogates for species. Different families may present similar
      roles in the ecosystems, with replacement of some taxa by other within the same
      guild. Spiders in tropical regions seem to have higher redundancy of functional
      roles and/or finer resource partitioning than in temperate regions. Although
      species and family diversity were higher in the tropics, functional diversity
      seems to be also influenced by altitude and habitat structure.

PMID- 21738773
TI  - Ras inhibition induces insulin sensitivity and glucose uptake.
AB  - BACKGROUND: Reduced glucose uptake due to insulin resistance is a pivotal
      mechanism in the pathogenesis of type 2 diabetes. It is also associated with
      increased inflammation. Ras inhibition downregulates inflammation in various
      experimental models. The aim of this study was to examine the effect of Ras
      inhibition on insulin sensitivity and glucose uptake, as well as its influence on
      type 2 diabetes development. METHODS AND FINDINGS: The effect of Ras inhibition
      on glucose uptake was examined both in vitro and in vivo. Ras was inhibited in
      cells transfected with a dominant-negative form of Ras or by 5-fluoro
      farnesylthiosalicylic acid (F-FTS), a small-molecule Ras inhibitor. The
      involvement of IkappaB and NF-kappaB in Ras-inhibited glucose uptake was
      investigated by immunoblotting. High fat (HF)-induced diabetic mice were treated
      with F-FTS to test the effect of Ras inhibition on induction of hyperglycemia.
      Each of the Ras-inhibitory modes resulted in increased glucose uptake, whether in
      insulin-resistant C2C12 myotubes in vitro or in HF-induced diabetic mice in vivo.
      Ras inhibition also caused increased IkappaB expression accompanied by decreased
      expression of NF-kappaB . In fat-induced diabetic mice treated daily with F-FTS,
      both the incidence of hyperglycemia and the levels of serum insulin were
      significantly decreased. CONCLUSIONS: Inhibition of Ras apparently induces a
      state of heightened insulin sensitization both in vitro and in vivo. Ras
      inhibition should therefore be considered as an approach worth testing for the
      treatment of type 2 diabetes.

PMID- 21738774
TI  - Efficacy of aquatain, a monomolecular film, for the control of malaria vectors in
      rice paddies.
AB  - BACKGROUND: Rice paddies harbour a large variety of organisms including larvae of
      malaria mosquitoes. These paddies are challenging for mosquito control because
      their large size, slurry and vegetation make it difficult to effectively apply a
      control agent. Aquatain, a monomolecular surface film, can be considered a
      suitable mosquito control agent for such breeding habitats due to its physical
      properties. The properties allow Aquatain to self-spread over a water surface and
      affect multiple stages of the mosquito life cycle. METHODOLOGY/PRINCIPAL
      FINDINGS: A trial based on a pre-test/post-test control group design evaluated
      the potential of Aquatain as a mosquito control agent at Ahero rice irrigation
      scheme in Kenya. After Aquatain application at a dose of 2 ml/m(2) on rice
      paddies, early stage anopheline larvae were reduced by 36%, and late stage
      anopheline larvae by 16%. However, even at a lower dose of 1 ml/m(2) there was a
      93.2% reduction in emergence of anopheline adults and 69.5% reduction in
      emergence of culicine adults. No pupation was observed in treated buckets that
      were part of a field bio-assay carried out parallel to the trial. Aquatain
      application saved nearly 1.7 L of water in six days from a water surface of 0.2
      m(2) under field conditions. Aquatain had no negative effect on rice plants as
      well as on a variety of non-target organisms, except backswimmers.
      CONCLUSIONS/SIGNIFICANCE: We demonstrated that Aquatain is an effective agent for
      the control of anopheline and culicine mosquitoes in irrigated rice paddies. The
      agent reduced densities of aquatic larval stages and, more importantly, strongly
      impacted the emergence of adult mosquitoes. Aquatain also reduced water loss due
      to evaporation. No negative impacts were found on either abundance of non-target
      organisms, or growth and development of rice plants. Aquatain, therefore, appears
      a suitable mosquito control tool for use in rice agro-ecosystems.

PMID- 21738775
TI  - Patterns of coupled theta activity in amygdala-hippocampal-prefrontal cortical
      circuits during fear extinction.
AB  - Signals related to fear memory and extinction are processed within brain pathways
      involving the lateral amygdala (LA) for formation of aversive stimulus
      associations, the CA1 area of the hippocampus for context-dependent modulation of
      these associations, and the infralimbic region of the medial prefrontal cortex
      (mPFC) for extinction processes. While many studies have addressed the
      contribution of each of these modules individually, little is known about their
      interactions and how they function as an integrated system. Here we show, by
      combining multiple site local field potential (LFP) and unit recordings in freely
      behaving mice in a fear conditioning paradigm, that theta oscillations may
      provide a means for temporally and functionally connecting these modules. Theta
      oscillations occurred with high specificity in the CA1-LA-mPFC network. Theta
      coupling increased between all areas during retrieval of conditioned fear, and
      declined during extinction learning. During extinction recall, theta coupling
      partly rebounded in LA-mPFC and CA1-mPFC, and remained at a low level in CA1-LA.
      Interfering with theta coupling through local electrical microstimulation in CA1
      LA affected conditioned fear and extinction recall depending on theta phase.
      These results support the hypothesis that theta coupling provides a means for
      inter-areal coordination in conditioned behavioral responsiveness. More
      specifically, theta oscillations seem to contribute to a population code
      indicating conditioned stimuli during recall of fear memory before and after
      extinction.

PMID- 21738776
TI  - A new system for the rapid collection of large numbers of developmentally staged
      zebrafish embryos.
AB  - The zebrafish is an excellent genetic and developmental model system used to
      study biology and disease. While the zebrafish model is associated with high
      fecundity, its reproductive potential has not been completely realized by
      scientists. One major issue is that embryo collection is inefficient. Here, we
      have developed an innovative breeding vessel designed to stimulate the natural
      reproductive behavior of the fish. This novel apparatus allows us to collect
      large numbers of developmentally synchronized embryos in brief and defined
      windows of time, and with minimal investments in labor and space. To demonstrate
      the efficacy of this approach, we placed three separate groups (n = 180) of fish
      in the vessel and allowed them to spawn for 10-minute intervals. During these
      trials, which were repeated three times, the fish produced 8600+/-917, 8400+/
      794, and 6800+/-1997 embryos, respectively. This level of embryo production is
      nearly twice what we were able to achieve when using conventional crossing
      equipment with some of the same fish, and it required significantly less room and
      time to set up and break down. This system overcomes major space and labor
      restrictions inherent in spawning equipment currently used in the field, and will
      greatly accelerate efforts to improve the scale and throughput of experiments.

PMID- 21738777
TI  - Comparison of the choice effect and the distance effect in a number-comparison
      task by FMRI.
AB  - Behavioral and neurophysiological studies of numerical comparisons have shown a
      "distance effect," whereby smaller numerical distances between two digits are
      associated with longer response times and higher activity in the parietal region.
      In this experiment, we introduced a two-choice condition (between either the
      smaller/lower or the larger/higher of two digits) and examined its effect on
      brain activity by fMRI. We observed longer response times and greater activity
      with the choice of smaller numbers ("choice effect") in several brain regions
      including the right temporo-parietal region, (pre)cuneus, superior temporal
      sulcus, precentral gyrus, superior frontal gyrus, bilateral insula, and anterior
      cingulate cortex. These regions correspond to areas that have been suggested to
      play a role in attentional shift and response conflict. However, brain activity
      associated with the distance effect disappeared even though the behavioral
      distance effect remained. Despite the absence of the distance effect on brain
      activity, several areas changed activity in relation to response time, including
      regions that were reported to change activity in both a distance effect and a
      reaction-time-related manner. The result suggested that the level of task load
      may change the activity of regions that are responsible for magnitude detection.

PMID- 21738778
TI  - Specific beta-tubulin isotypes can functionally enhance or diminish epothilone B
      sensitivity in non-small cell lung cancer cells.
AB  - Epothilones are a new class of microtubule stabilizing agents with promising
      preclinical and clinical activity. Their cellular target is beta-tubulin and
      factors influencing intrinsic sensitivity to epothilones are not well understood.
      In this study, the functional significance of specific beta-tubulin isotypes in
      intrinsic sensitivity to epothilone B was investigated using siRNA gene knockdown
      against betaII-, betaIII- or betaIVb-tubulins in two independent non-small cell
      lung cancer (NSCLC) cell lines, NCI-H460 and Calu-6. Drug-treated clonogenic
      assays showed that sensitivity to epothilone B was not altered following
      knockdown of betaII-tubulin in both NSCLC cell lines. In contrast, knockdown of
      betaIII-tubulin significantly increased sensitivity to epothilone B.
      Interestingly, betaIVb-tubulin knockdowns were significantly less sensitive to
      epothilone B, compared to mock- and control siRNA cells. Cell cycle analysis of
      betaIII-tubulin knockdown cells showed a higher percentage of cell death with
      epothilone B concentrations as low as 0.5 nM. In contrast, betaIVb-tubulin
      knockdown cells displayed a decrease in epothilone B-induced G(2)-M cell cycle
      accumulation compared to control siRNA cells. Importantly, betaIII-tubulin
      knockdowns displayed a significant dose-dependent increase in the percentage of
      apoptotic cells upon treatment with epothilone B, as detected using caspase 3/7
      activity and Annexin-V staining. Higher concentrations of epothilone B were
      required to induce apoptosis in the betaIVb-tubulin knockdowns compared to
      control siRNA, highlighting a potential mechanism underlying decreased
      sensitivity to this agent. This study demonstrates that specific beta-tubulin
      isotypes can influence sensitivity to epothilone B and may influence differential
      sensitivity to this promising new agent.

PMID- 21738779
TI  - Warming increases the spread of an invasive thistle.
AB  - BACKGROUND: Global warming and shifted precipitation regimes increasingly affect
      species abundances and distributions worldwide. Despite a large literature on
      species' physiological, phenological, growth, and reproductive responses to such
      climate change, dispersal is rarely examined. Our study aims to test whether the
      dispersal ability of a non-native, wind-dispersed plant species is affected by
      climate change, and to quantify the ramifications for future invasion spread
      rates. METHODOLOGY/PRINCIPAL FINDINGS: We experimentally increased temperature
      and precipitation in a two-cohort, factorial field study (n = 80). We found an
      overwhelming warming effect on plant life history: warming not only improved
      emergence, survival, and reproduction of the thistle Carduus nutans, but also
      elevated plant height, which increased seed dispersal distances. Using spatial
      population models, we demonstrate that these empirical warming effects on
      demographic vital rates, and dispersal parameters, greatly exacerbate spatial
      spread. Predicted levels of elevated winter precipitation decreased seed
      production per capitulum, but this only slightly offset the warming effect on
      spread. Using a spread rate decomposition technique (c*-LTRE), we also found that
      plant height-mediated changes in dispersal contribute most to increased spread
      rate under climate change. CONCLUSIONS/SIGNIFICANCE: We found that both dispersal
      and spread of this wind-dispersed plant species were strongly impacted by climate
      change. Dispersal responses to climate change can improve, or diminish, a
      species' ability to track climate change spatially, and should not be overlooked.
      Methods that combine both demographic and dispersal responses thus will be an
      invaluable complement to projections of suitable habitat under climate change.

PMID- 21738780
TI  - NFkappaB1 and NFkappaBIA polymorphisms are associated with increased risk for
      sporadic colorectal cancer in a southern Chinese population.
AB  - BACKGROUND: Nuclear factor kappaB (NFkappaB) plays a key role in the regulation
      of apoptosis. The function of NFkappaB is inhibited by binding to NFkappaB
      inhibitor (IkappaB), and disruption of the balance of NFkappaB and IkappaB is
      related to the development of many diseases, including tumors. Therefore, we
      hypothesized that the NFkappaB1 (-94del/insATTG) and NFkappaBIA (2758 A>G)
      polymorphisms were associated with colorectal cancer (CRC) susceptibility.
      METHODS: In a hospital-based case-control study of 1001 CRC patients and 1005
      cancer-free controls frequency matched by age and sex, we genotyped polymorphisms
      using polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) method and performed luciferase assays and Western blotting analysis to
      identify whether genetic variants in NFkappaBIA alter its gene expressions and
      functions and thus cancer risk. RESULTS: We found that both NFkappaB1-94
      ins/delATTG and NFkappaBIA 2758 A>G polymorphisms were correlated with CRC risk
      (OR = 1.47; 95%CI = 1.14-1.86, and OR = 1.38; 95% CI = 1.14-1.66, respectively).
      Furthermore, when evaluated these two polymorphisms together, the combined
      genotypes with 2 variant (risk) alleles (2758GG and -94ins/ins+del/ins) were
      associated with an increased risk of CRC (OR = 1.71; 95% CI = 1.23-2.38) compared
      to 0 variant, and the significant trend for 2 variant (risk) alleles were more
      pronounced among subgroups of aged <60 years, women, never drinkers, never
      smokers, persons with a normal BMI and those with a family history of
      cancer(P(trend)<0.01). Moreover, luciferase assays showed that the G allele in
      the 3'UTR significantly decreased NFkappaBIA mRNA stability and the A allele
      regulation by miRNA449a in vitro and that the NFkappaBIA protein expression
      levels of the AA+AG variant carriers were significantly higher in peritumoral
      tissues than those of the 2758GG genotype. CONCLUSION: NFkappaB1 and NFkappaBIA
      polymorphisms appear to jointly contribute to risk of CRC. These two variants may
      be a genetic modifier for CRC susceptibility in this southern Chinese population.

PMID- 21738781
TI  - Phosphoproteomic profiling of in vivo signaling in liver by the mammalian target
      of rapamycin complex 1 (mTORC1).
AB  - BACKGROUND: Our understanding of signal transduction networks in the
      physiological context of an organism remains limited, partly due to the technical
      challenge of identifying serine/threonine phosphorylated peptides from complex
      tissue samples. In the present study, we focused on signaling through the
      mammalian target of rapamycin (mTOR) complex 1 (mTORC1), which is at the center
      of a nutrient- and growth factor-responsive cell signaling network. Though
      studied extensively, the mechanisms involved in many mTORC1 biological functions
      remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We developed a
      phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat
      liver homogenates. Using the anticancer drug rapamycin, the only known target of
      which is mTORC1, we characterized signaling in liver from rats in which the
      complex was maximally activated by refeeding following 48 hr of starvation. Using
      protein and peptide fractionation methods, TiO(2) affinity purification of
      phosphopeptides and mass spectrometry, we reproducibly identified and quantified
      over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive
      phosphorylation events, we identified 62 new rapamycin-responsive candidate
      phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We
      observed similar proportions of increased and reduced phosphorylation in response
      to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway
      components among rapamycin-sensitive phosphopeptide candidates.
      CONCLUSIONS/SIGNIFICANCE: In addition to identifying potential new mTORC1
      mediated phosphorylation events, and providing information relevant to the
      biology of this signaling network, our experimental and analytical approaches
      indicate the feasibility of large-scale phosphoproteomic profiling of tissue
      samples to study physiological signaling events in vivo.

PMID- 21738782
TI  - VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially
      inhibit growth and are neutralized by cognate VapB antitoxins.
AB  - The chromosome of Mycobacterium tuberculosis (Mtb) encodes forty seven toxin
      antitoxin modules belonging to the VapBC family. The role of these modules in the
      physiology of Mtb and the function(s) served by their expansion are unknown. We
      investigated ten vapBC modules from Mtb and the single vapBC from M. smegmatis.
      Of the Mtb vapCs assessed, only Rv0549c, Rv0595c, Rv2549c and Rv2829c were toxic
      when expressed from a tetracycline-regulated promoter in M. smegmatis. The same
      genes displayed toxicity when conditionally expressed in Mtb. Toxicity of Rv2549c
      in M. smegmatis correlated with the level of protein expressed, suggesting that
      the VapC level must exceed a threshold for toxicity to be observed. In addition,
      the level of Rv2456 protein induced in M. smegmatis was markedly lower than
      Rv2549c, which may account for the lack of toxicity of this and other VapCs
      scored as 'non-toxic'. The growth inhibitory effects of toxic VapCs were
      neutralized by expression of the cognate VapB as part of a vapBC operon or from a
      different chromosomal locus, while that of non-cognate antitoxins did not. These
      results demonstrated a specificity of interaction between VapCs and their cognate
      VapBs, a finding corroborated by yeast two-hybrid analyses. Deletion of selected
      vapC or vapBC genes did not affect mycobacterial growth in vitro, but rendered
      the organisms more susceptible to growth inhibition following toxic VapC
      expression. However, toxicity of 'non-toxic' VapCs was not unveiled in deletion
      mutant strains, even when the mutation eliminated the corresponding cognate VapB,
      presumably due to insufficient levels of VapC protein. Together with the
      ribonuclease (RNase) activity demonstrated for Rv0065 and Rv0617--VapC proteins
      with similarity to Rv0549c and Rv3320c, respectively--these results suggest that
      the VapBC family potentially provides an abundant source of RNase activity in
      Mtb, which may profoundly impact the physiology of the organism.

PMID- 21738783
TI  - Genomic and protein structural maps of adaptive evolution of human influenza A
      virus to increased virulence in the mouse.
AB  - Adaptive evolution is characterized by positive and parallel, or repeated
      selection of mutations. Mouse adaptation of influenza A virus (IAV) produces
      virulent mutants that demonstrate positive and parallel evolution of mutations in
      the hemagglutinin (HA) receptor and non-structural protein 1 (NS1) interferon
      antagonist genes. We now present a genomic analysis of all 11 genes of 39 mouse
      adapted IAV variants from 10 replicate adaptation experiments. Mutations were
      mapped on the primary and structural maps of each protein and specific mutations
      were validated with respect to virulence, replication, and RNA polymerase
      activity. Mouse adapted (MA) variants obtained after 12 or 20-21 serial
      infections acquired on average 5.8 and 7.9 nonsynonymous mutations per genome of
      11 genes, respectively. Among a total of 115 nonsynonymous mutations, 51
      demonstrated properties of natural selection including 27 parallel mutations. The
      greatest degree of parallel evolution occurred in the HA receptor and
      ribonucleocapsid components, polymerase subunits (PB1, PB2, PA) and NP. Mutations
      occurred in host nuclear trafficking factor binding sites as well as sites of
      virus-virus protein subunit interaction for NP, NS1, HA and NA proteins. Adaptive
      regions included cap binding and endonuclease domains in the PB2 and PA
      polymerase subunits. Four mutations in NS1 resulted in loss of binding to the
      host cleavage and polyadenylation specificity factor (CPSF30) suggesting that a
      reduction in inhibition of host gene expression was being selected. The most
      prevalent mutations in PB2 and NP were shown to increase virulence but differed
      in their ability to enhance replication and demonstrated epistatic effects.
      Several positively selected RNA polymerase mutations demonstrated increased
      virulence associated with >300% enhanced polymerase activity. Adaptive mutations
      that control host range and virulence were identified by their repeated selection
      to comprise a defined model for studying IAV evolution to increased virulence in
      the mouse.

PMID- 21738784
TI  - Effects of dibutyryl cyclic-AMP on survival and neuronal differentiation of
      neural stem/progenitor cells transplanted into spinal cord injured rats.
AB  - Neural stem/progenitor cells (NSPCs) have great potential as a cell replacement
      therapy for spinal cord injury. However, poor control over transplant cell
      differentiation and survival remain major obstacles. In this study, we asked
      whether dibutyryl cyclic-AMP (dbcAMP), which was shown to induce up to 85% in
      vitro differentiation of NSPCs into neurons would enhance survival of
      transplanted NSPCs through prolonged exposure either in vitro or in vivo through
      the controlled release of dbcAMP encapsulated within poly(lactic-co-glycolic
      acid) (PLGA) microspheres and embedded within chitosan guidance channels. NSPCs,
      seeded in fibrin scaffolds within the channels, differentiated in vitro to
      betaIII-tubulin positive neurons by immunostaining and mRNA expression, in
      response to dbcAMP released from PLGA microspheres. After transplantation in
      spinal cord injured rats, the survival and differentiation of NSPCs was
      evaluated. Untreated NSPCs, NSPCs transplanted with dbcAMP-releasing
      microspheres, and NSPCs pre-differentiated with dbcAMP for 4 days in vitro were
      transplanted after rat spinal cord transection and assessed 2 and 6 weeks later.
      Interestingly, NSPC survival was highest in the dbcAMP pre-treated group, having
      approximately 80% survival at both time points, which is remarkable given that
      stem cell transplantation often results in less than 1% survival at similar
      times. Importantly, dbcAMP pre-treatment also resulted in the greatest number of
      in vivo NSPCs differentiated into neurons (37+/-4%), followed by dbcAMP
      microsphere treated NSPCs (27+/-14%) and untreated NSPCs (15+/-7%). The reverse
      trend was observed for NSPC-derived oligodendrocytes and astrocytes, with these
      populations being highest in untreated NSPCs. This combination strategy of stem
      cell-loaded chitosan channels implanted in a fully transected spinal cord
      resulted in extensive axonal regeneration into the injury site, with improved
      functional recovery after 6 weeks in animals implanted with pre-differentiated
      stem cells in chitosan channels.

PMID- 21738785
TI  - Multiple indices of diffusion identifies white matter damage in mild cognitive
      impairment and Alzheimer's disease.
AB  - The study of multiple indices of diffusion, including axial (DA), radial (DR) and
      mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in
      Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial
      statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic
      MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients.
      Significantly higher DA was found in MCIna subjects compared to healthy elders in
      the right posterior cingulum/precuneus. Significantly higher DA was also found in
      MCIa subjects compared to healthy elders in the left prefrontal cortex,
      particularly in the forceps minor and uncinate fasciculus. In the MCIa versus
      MCIna comparison, significantly higher DA was found in large areas of the left
      prefrontal cortex. For AD patients, the overlap of FA and DR changes and the
      overlap of FA and MD changes were seen in temporal, parietal and frontal lobes,
      as well as the corpus callosum and fornix. Analysis of differences between the AD
      versus MCIna, and AD versus MCIa contrasts, highlighted regions that are
      increasingly compromised in more severe disease stages. Microstructural damage
      independent of gross tissue loss was widespread in later disease stages. Our
      findings suggest a scheme where WM damage begins in the core memory network of
      the temporal lobe, cingulum and prefrontal regions, and spreads beyond these
      regions in later stages. DA and MD indices were most sensitive at detecting early
      changes in MCIa.

PMID- 21738786
TI  - Validation of case-finding algorithms derived from administrative data for
      identifying adults living with human immunodeficiency virus infection.
AB  - OBJECTIVE: We sought to validate a case-finding algorithm for human
      immunodeficiency virus (HIV) infection using administrative health databases in
      Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using
      combinations of physician billing claims, hospital and emergency room separations
      and prescription drug claims. We determined the test characteristics of each
      algorithm over various time frames for identifying HIV infection, using data
      abstracted from the charts of 2,040 randomly selected patients receiving care at
      two medical practices in Toronto, Ontario as the reference standard. RESULTS:
      With the exception of algorithms using only a single physician claim, the
      specificity of all algorithms exceeded 99%. An algorithm consisting of three
      physician claims over a three year period had a sensitivity and specificity of
      96.2% (95% CI 95.2%-97.9%) and 99.6% (95% CI 99.1%-99.8%), respectively.
      Application of the algorithm to the province of Ontario identified 12,179 HIV
      infected patients in care for the period spanning April 1, 2007 to March 31,
      2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can
      accurately identify adults living with HIV. A relatively simple "3 claims in 3
      years" definition can be used for assembling a population-based cohort and
      facilitating future research examining trends in health service use and outcomes
      among HIV-infected adults in Ontario.

PMID- 21738787
TI  - Microbial diversity in the midguts of field and lab-reared populations of the
      European corn borer Ostrinia nubilalis.
AB  - BACKGROUND: Insects are associated with microorganisms that contribute to the
      digestion and processing of nutrients. The European Corn Borer (ECB) is a moth
      present world-wide, causing severe economical damage as a pest on corn and other
      crops. In the present work, we give a detailed view of the complexity of the
      microorganisms forming the ECB midgut microbiota with the objective of comparing
      the biodiversity of the midgut-associated microbiota and explore their potential
      as a source of genes and enzymes with biotechnological applications.
      METHODOLOGICAL/PRINCIPAL FINDINGS: A high-throughput sequencing approach has been
      used to identify bacterial species, genes and metabolic pathways, particularly
      those involved in plant-matter degradation, in two different ECB populations
      (field-collected vs. lab-reared population with artificial diet). Analysis of the
      resulting sequences revealed the massive presence of Staphylococcus warneri and
      Weissella paramesenteroides in the lab-reared sample. This enabled us to
      reconstruct both genomes almost completely. Despite the apparently low diversity,
      208 different genera were detected in the sample, although most of them at very
      low frequency. By contrast, the natural population exhibited an even higher
      taxonomic diversity along with a wider array of cellulolytic enzyme families.
      However, in spite of the differences in relative abundance of major taxonomic
      groups, not only did both metagenomes share a similar functional profile but also
      a similar distribution of non-redundant genes in different functional categories.
      CONCLUSIONS/SIGNIFICANCE: Our results reveal a highly diverse pool of bacterial
      species in both O. nubilalis populations, with major differences: The lab-reared
      sample is rich in gram-positive species (two of which have almost fully sequenced
      genomes) while the field sample harbors mainly gram-negative species and has a
      larger set of cellulolytic enzymes. We have found a clear relationship between
      the diet and the midgut microbiota, which reveals the selection pressure of food
      on the community of intestinal bacteria.

PMID- 21738788
TI  - Impaired spleen formation perturbs morphogenesis of the gastric lobe of the
      pancreas.
AB  - Despite the extensive use of the mouse as a model for studies of pancreas
      development and disease, the development of the gastric pancreatic lobe has been
      largely overlooked. In this study we use optical projection tomography to provide
      a detailed three-dimensional and quantitative description of pancreatic growth
      dynamics in the mouse. Hereby, we describe the epithelial and mesenchymal events
      leading to the formation of the gastric lobe of the pancreas. We show that this
      structure forms by perpendicular growth from the dorsal pancreatic epithelium
      into a distinct lateral domain of the dorsal pancreatic mesenchyme. Our data
      support a role for spleen organogenesis in the establishment of this mesenchymal
      domain and in mice displaying perturbed spleen development, including Dh +/-,
      Bapx1-/- and Sox11-/-, gastric lobe development is disturbed. We further show
      that the expression profile of markers for multipotent progenitors is delayed in
      the gastric lobe as compared to the splenic and duodenal pancreatic lobes.
      Altogether, this study provides new information regarding the developmental
      dynamics underlying the formation of the gastric lobe of the pancreas and
      recognizes lobular heterogeneities regarding the time course of pancreatic
      cellular differentiation. Collectively, these data are likely to constitute
      important elements in future interpretations of the developing and/or diseased
      pancreas.

PMID- 21738789
TI  - Iminosugar-based inhibitors of glucosylceramide synthase increase brain
      glycosphingolipids and survival in a mouse model of Sandhoff disease.
AB  - The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage
      disorders for which there are no effective therapies. A potential approach is
      substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS)
      to decrease the synthesis of glucosylceramide and related glycosphingolipids that
      accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant
      iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse
      model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the
      visceral organs and CNS. As expected, oral administration of the drug inhibited
      hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a
      slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels.
      The increase in brain glucosylceramide levels might be due to concurrent
      inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were
      observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these
      unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless
      delayed the loss of motor function and coordination and extended the lifespan of
      the Sandhoff mice. These results suggest that the CNS benefits observed in the
      Sandhoff mice might not necessarily be due to substrate reduction therapy but
      rather to off-target effects.

PMID- 21738790
TI  - Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and
      motor function.
AB  - SIRT1 plays crucial roles in glucose and lipid metabolism, and has various
      functions in different tissues including brain. The brain-specific SIRT1 knockout
      mice display defects in somatotropic signaling, memory and synaptic plasticity.
      And the female mice without SIRT1 in POMC neuron are more sensitive to diet
      induced obesity. Here we created transgenic mice overexpressing SIRT1 in striatum
      and hippocampus under the control of CaMKIIalpha promoter. These mice, especially
      females, exhibited increased fat accumulation accompanied by significant
      upregulation of adipogenic genes in white adipose tissue. Glucose tolerance of
      the mice was also impaired with decreased Glut4 mRNA levels in muscle. Moreover,
      the SIRT1 overexpressing mice showed decreased energy expenditure, and
      concomitantly mitochondria-related genes were decreased in muscle. In addition,
      these mice showed unusual spontaneous physical activity pattern, decreased
      activity in open field and rotarod performance. Further studies demonstrated that
      SIRT1 deacetylated IRS-2, and upregulated phosphorylation level of IRS-2 and
      ERK1/2 in striatum. Meanwhile, the neurotransmitter signaling in striatum and the
      expression of endocrine hormones in hypothalamus and serum T3, T4 levels were
      altered. Taken together, our findings demonstrate that SIRT1 in forebrain
      regulates lipid/glucose metabolism and motor function.

PMID- 21738791
TI  - RIG-I mediates innate immune response in mouse neurons following Japanese
      encephalitis virus infection.
AB  - BACKGROUND: Neuroinflammation associated with Japanese encephalitis (JE) is
      mainly due to the activation of glial cells with subsequent release of
      proinflammatory mediators from them. The recognition of viral RNA, in part, by
      the pattern recognition receptor retinoic acid-inducible gene I (RIG-I) has been
      indicated to have a role in such processes. Even though neurons are also known to
      express this receptor, its role after JE virus (JEV) infections is yet to be
      elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Upon infecting murine neuroblastoma
      cells and primary cortical neurons with JEV the expression profile of key
      proinflammatory cyto/chemokines were analyzed by qRT-PCR and bead array, both
      before and after ablation of RIG-I. Immunoblotting was performed to evaluate the
      levels of key molecules downstream to RIG-I leading to production of
      proinflammatory mediators. Changes in the intracellular viral antigen expression
      were confirmed by intracellular staining and immunoblotting. JEV infection
      induced neuronal expression of IL-6, IL-12p70, MCP-1, IP-10 and TNF-alpha in a
      time-dependent manner, which showed significant reduction upon RIG-I ablation.
      Molecules downstream to RIG-I showed significant changes upon JEV-infection, that
      were modulated following RIG-I ablation. Ablation of RIG-I in neurons also
      increased their susceptibility to JEV. CONCLUSIONS/SIGNIFICANCE: In this study we
      propose that neurons are one of the potential sources of proinflammatory
      cyto/chemokines in JEV-infected brain that are produced via RIG-I dependent
      pathways. Ablation of RIG-I in neurons leads to increased viral load and reduced
      release of the cyto/chemokines.

PMID- 21738792
TI  - PP1 forms an active complex with TLRR (lrrc67), a putative PP1 regulatory
      subunit, during the early stages of spermiogenesis in mice.
AB  - Mammalian spermatogenesis is a highly regulated developmental pathway that
      demands dramatic rearrangement of the cytoskeleton of the male germ cell. We have
      described previously a leucine rich repeat protein, TLRR (also known as lrrc67),
      which is associated with the spermatid cytoskeleton in mouse testis and is a
      binding partner of protein phosphatase-1 (PP1), an extremely well conserved
      signaling molecule. The activity of PP1 is modulated by numerous specific
      regulators of which TLRR is a candidate. In this study we measured the
      phosphatase activity of the TLRR-PP1 complex in the adult and the developing
      mouse testis, which contains varying populations of developing germ cell types,
      in order to determine whether TLRR acts as an activator or an inhibitor of PP1
      and whether the phosphatase activity of this complex is developmentally regulated
      during spermatogenesis. Additionally, we assayed the ability of bacterially
      expressed TLRR to affect the enzymatic activity of PP1. Furthermore, we examined
      phosphorylation of TLRR, and elements of the spermatid cytoskeleton during the
      first wave of spermatogenesis in the developing testis. We demonstrate here that
      the TLRR complex is associated with a phosphatase activity in adult mouse testis.
      The relative phosphatase activity of this complex appears to reach a peak at
      about 21 days after birth, when pachytene spermatocytes and round spermatids are
      abundant in the seminiferous epithelium of the mouse testis. TLRR, in addition to
      tubulin and kinesin-1B, is phosphorylated during the first wave of
      spermatogenesis. These findings indicate that the TLRR-PP1 complex is active
      prior to translocation of TLRR toward the sperm flagella and that TLRR, and
      constituents of the spermatid cytoskeleton, may be subject to regulation by
      reversible phosphorylation during spermatogenesis in murine testis.

PMID- 21738793
TI  - Association pattern of interleukin-1 receptor-associated kinase-4 gene
      polymorphisms with allergic rhinitis in a Han Chinese population.
AB  - OBJECTIVE: Interleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase
      that is essential for NF-kB activation in Toll-like receptor and T-cell receptor
      signaling pathways, indicating a possible crosstalk between innate and acquired
      immunities. We attempted to determine whether the polymorphisms in the
      Interleukin-1 receptor-associated kinase-4 (IRAK-4) gene are associated with
      allergic rhinitis (AR) in the Han Chinese population. METHODS: A population of
      379 patients with AR and 333 healthy controls was studied. Blood was drawn for
      DNA extraction and total serum immunoglobulin E (IgE). A total of 11 single
      nucleotide polymorphisms (SNPs) in IRAK-4 were selected and individually
      genotyped. RESULTS: Significant allelic differences between cases and controls
      were obtained for the SNP of rs3794262 in the IRAK-4 gene. In the stratified
      analysis for gender, two SNPs (rs4251431 and rs6582484) in males appeared as
      significant associations. Subgroup analysis for the presence of different
      allergen sensitivities displayed associations only in the house dust mite
      allergic cohorts (rs3794262, rs4251481). None of the selected SNPs in IRAK-4 was
      associated with total IgE level. The haplotype analysis indicated GCCTGCGA was
      significantly associated with AR. The SNP-SNP interaction information analysis
      indicated that the selected sets of polymorphisms had no synergistic effect.
      CONCLUSIONS: Our findings did not support the potential contribution of the IRAK
      4 gene to serum IgE levels. However, the results demonstrated a gender- and
      allergen-dependant association pattern between polymorphisms in IRAK-4 and AR in
      Chinese population.

PMID- 21738794
TI  - Functional characterization of the octenol receptor neuron on the maxillary palps
      of the yellow fever mosquito, Aedes aegypti.
AB  - BACKGROUND: 1-Octen-3-ol (octenol) is a common attractant released by vertebrates
      which in combination with carbon dioxide (CO(2)) attracts hematophagous
      arthropods including mosquitoes. A receptor neuron contained within basiconic
      sensilla on the maxillary palps of adult mosquitoes responds selectively to 1
      octen-3-ol. Recently, an odorant receptor (AaegOR8) known to occur on the
      maxillary palps was expressed in a heterologous system and demonstrated to be
      selectively sensitive to (R)-(-)-1-octen-3-ol, one of two enantiomeric forms.
      Lesser responses were elicited by stimulation with the (S)-enantiomer and various
      structural analogs. METHODOLOGY/PRINCIPAL FINDINGS: Here we characterize the
      specificity of the octenol receptor neuron in the yellow fever mosquito, Aedes
      aegypti (L.), in vivo using single cell recordings. The octenol neuron is
      exquisitely sensitive to (R)-(-)-1-octen-3-ol; comparable responses to (S)-(+)-1
      octen-3-ol were elicited only at stimulus doses over 100* that required for the
      (R)-enantiomer. An intermediate response closer to that elicited by the (R)-(-)
      enantiomer was elicited by racemic 1-octen-3-ol. Small structural changes in (R)
      (-)-1-octen-3-ol resulted in large decreases in responses. Increases in spike
      activity were also elicited in the octenol neuron by 2-undecanone, a known
      repellent; other repellents (DEET, IR3535 and picaridin) were inactive.
      CONCLUSIONS/SIGNIFICANCE: The results of our electrophysiological studies of the
      octenol receptor neuron in vivo approximates results of a previous study of the
      octenol receptor (AaegOR8 with its obligate partner Aaeg?ORco) expressed
      heterologously in Xenopus oocytes. By comparison of our current results with
      those of the heterologous expression study, we conclude that specificity of the
      octenol receptor neuron can be explained largely by characteristics of the OR
      alone without other associated proteins present in vivo. Our findings show that
      repellents may have specific stimulatory effects on receptor neurons and support
      the notion of repellents as modulators of mosquito odorant receptor activity.

PMID- 21738795
TI  - Identification and characterization of NF-Y transcription factor families in the
      monocot model plant Brachypodium distachyon.
AB  - BACKGROUND: Nuclear Factor Y (NF-Y) is a heterotrimeric transcription factor
      composed of NF-YA, NF-YB and NF-YC proteins. Using the dicot plant model system
      Arabidopsis thaliana (Arabidopsis), NF-Y were previously shown to control a
      variety of agronomically important traits, including drought tolerance, flowering
      time, and seed development. The aim of the current research was to identify and
      characterize NF-Y families in the emerging monocot model plant Brachypodium
      distachyon (Brachypodium) with the long term goal of assisting in the translation
      of known dicot NF-Y functions to the grasses. METHODOLOGY/PRINCIPAL FINDINGS: We
      identified, annotated, and further characterized 7 NF-YA, 17 NF-YB, and 12 NF-YC
      proteins in Brachypodium (BdNF-Y). By examining phylogenetic relationships,
      orthology predictions, and tissue-specific expression patterns for all 36 BdNF-Y,
      we proposed numerous examples of likely functional conservation between dicots
      and monocots. To test one of these orthology predictions, we demonstrated that a
      BdNF-YB with predicted orthology to Arabidopsis floral-promoting NF-Y proteins
      can rescue a late flowering Arabidopsis mutant. CONCLUSIONS/SIGNIFICANCE: The
      Brachypodium genome encodes a similar complement of NF-Y to other sequenced
      angiosperms. Information regarding NF-Y phylogenetic relationships, predicted
      orthologies, and expression patterns can facilitate their study in the grasses.
      The current data serves as an entry point for translating many NF-Y functions
      from dicots to the genetically tractable monocot model system Brachypodium. In
      turn, studies of NF-Y function in Brachypodium promise to be more readily
      translatable to the agriculturally important grasses.

PMID- 21738796
TI  - Induction of immune mediators in glioma and prostate cancer cells by non-lethal
      photodynamic therapy.
AB  - BACKGROUND: Photodynamic therapy (PDT) uses the combination of photosensitizing
      drugs and harmless light to cause selective damage to tumor cells. PDT is
      therefore an option for focal therapy of localized disease or for otherwise
      unresectable tumors. In addition, there is increasing evidence that PDT can
      induce systemic anti-tumor immunity, supporting control of tumor cells, which
      were not eliminated by the primary treatment. However, the effect of non-lethal
      PDT on the behavior and malignant potential of tumor cells surviving PDT is
      molecularly not well defined. METHODOLOGY/PRINCIPAL FINDINGS: Here we have
      evaluated changes in the transcriptome of human glioblastoma (U87, U373) and
      human (PC-3, DU145) and murine prostate cancer cells (TRAMP-C1, TRAMP-C2) after
      non-lethal PDT in vitro and in vivo using oligonucleotide microarray analyses. We
      found that the overall response was similar between the different cell lines and
      photosensitizers both in vitro and in vivo. The most prominently upregulated
      genes encoded proteins that belong to pathways activated by cellular stress or
      are involved in cell cycle arrest. This response was similar to the rescue
      response of tumor cells following high-dose PDT. In contrast, tumor cells dealing
      with non-lethal PDT were found to significantly upregulate a number of immune
      genes, which included the chemokine genes CXCL2, CXCL3 and IL8/CXCL8 as well as
      the genes for IL6 and its receptor IL6R, which can stimulate proinflammatory
      reactions, while IL6 and IL6R can also enhance tumor growth. CONCLUSIONS: Our
      results indicate that PDT can support anti-tumor immune responses and is,
      therefore, a rational therapy even if tumor cells cannot be completely eliminated
      by primary phototoxic mechanisms alone. However, non-lethal PDT can also
      stimulate tumor growth-promoting autocrine loops, as seen by the upregulation of
      IL6 and its receptor. Thus the efficacy of PDT to treat tumors may be improved by
      controlling unwanted and potentially deleterious growth-stimulatory pathways.

PMID- 21738797
TI  - Quality of life and related factors among HIV-positive spouses from
      serodiscordant couples under antiretroviral therapy in Henan Province, China.
AB  - OBJECTIVE: To describe the quality of life and related factors in HIV-positive
      spouses undergoing ART from discordant couples. METHODS: A cross-sectional study
      was conducted among 1,009 HIV-positive spouses from serodiscordant couples in
      Zhumadian, Henan Province, between October 1, 2008 and March 31, 2009. HIV
      positive spouses were interviewed by local health professionals. Quality of life
      was evaluated by WHOQOL (Chinese Version). A multiple linear regression model was
      used to analyze the related factors. RESULTS: The majority of subjects were
      female (56.39%), had received a high school education (44%), were of Han
      ethnicity (98.41%), and were farmers (90.09%); the median time period of
      receiving ART was 3.92 years. The physical, psychological, social, and
      environmental QOL scores of the subjects were 12.91+/-1.95, 12.35+/-1.80, 13.96+/
      2.43, and 12.45+/-1.91 respectively. The multiple linear regression model
      identified the physical domain related factors to be CD4 count, educational
      level, and occupation; psychological domain related factors include age,
      educational level, and reported STD symptom; social domain related factors
      included education level; and environmental domain related factors included
      education level, reported STD symptoms, and occupation. CONCLUSION: Being
      younger, a farmer, having a lower level of education, a reported STD symptom, or
      lower CD4 count, could decrease one's quality of life, suggesting that the use of
      blanket ART programs alone may not necessarily improve quality of life. Subjects
      received lower scores in the psychological domain, suggesting that psychological
      intervention may also need to be strengthened.

PMID- 21738798
TI  - Lack of evidence for an association between Iridovirus and colony collapse
      disorder.
AB  - Colony collapse disorder (CCD) is characterized by the unexplained losses of
      large numbers of adult worker bees (Apis mellifera) from apparently healthy
      colonies. Although infections, toxins, and other stressors have been associated
      with the onset of CCD, the pathogenesis of this disorder remains obscure.
      Recently, a proteomics study implicated a double-stranded DNA virus, invertebrate
      iridescent virus (Family Iridoviridae) along with a microsporidium (Nosema sp.)
      as the cause of CCD. We tested the validity of this relationship using two
      independent methods: (i) we surveyed healthy and CCD colonies from the United
      States and Israel for the presence of members of the Iridovirus genus and (ii) we
      reanalyzed metagenomics data previously generated from RNA pools of CCD colonies
      for the presence of Iridovirus-like sequences. Neither analysis revealed any
      evidence to suggest the presence of an Iridovirus in healthy or CCD colonies.

PMID- 21738799
TI  - Fitness cost of resistance to Bt cotton linked with increased gossypol content in
      pink bollworm larvae.
AB  - Fitness costs of resistance to Bacillus thuringiensis (Bt) crops occur in the
      absence of Bt toxins, when individuals with resistance alleles are less fit than
      individuals without resistance alleles. As costs of Bt resistance are common,
      refuges of non-Bt host plants can delay resistance not only by providing
      susceptible individuals to mate with resistant individuals, but also by selecting
      against resistance. Because costs typically vary across host plants, refuges with
      host plants that magnify costs or make them less recessive could enhance
      resistance management. Limited understanding of the physiological mechanisms
      causing fitness costs, however, hampers attempts to increase costs. In several
      major cotton pests including pink bollworm (Pectinophora gossypiella), resistance
      to Cry1Ac cotton is associated with mutations altering cadherin proteins that
      bind this toxin in susceptible larvae. Here we report that the concentration of
      gossypol, a cotton defensive chemical, was higher in pink bollworm larvae with
      cadherin resistance alleles than in larvae lacking such alleles. Adding gossypol
      to the larval diet decreased larval weight and survival, and increased the
      fitness cost affecting larval growth, but not survival. Across cadherin
      genotypes, the cost affecting larval growth increased as the gossypol
      concentration of larvae increased. These results suggest that increased
      accumulation of plant defensive chemicals may contribute to fitness costs
      associated with resistance to Bt toxins.

PMID- 21738800
TI  - Konzo: from poverty, cassava, and cyanogen intake to toxico-nutritional
      neurological disease.
AB  - Konzo is a distinct neurological entity with selective upper motor neuron damage,
      characterized by an abrupt onset of an irreversible, non-progressive, and
      symmetrical spastic para/tetraparesis. Despite its severity, konzo remains a
      neglected disease. The disease is associated with high dietary cyanogen
      consumption from insufficiently processed roots of bitter cassava combined with a
      protein-deficient diet. Epidemics occur when these conditions coincide at times
      of severe food shortage. Up to 1993, outbreaks in poor rural areas in Africa
      contributed to more than 3,700 cases of konzo. The number of affected people is
      underestimated. From unofficial reports, the number of cases was estimated to be
      at least 100,000 in 2000, in contrast to the 6,788 cases reported up to 2009 from
      published papers.

PMID- 21738801
TI  - Rabies-related knowledge and practices among persons at risk of bat exposures in
      Thailand.
AB  - BACKGROUND: Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of
      lyssavirus circulation has recently emerged in Southeast Asian bats. A cross
      sectional study was conducted in Thailand to assess rabies-related knowledge and
      practices among persons regularly exposed to bats and bat habitats. The
      objectives were to identify deficiencies in rabies awareness, describe the
      occurrence of bat exposures, and explore factors associated with transdermal bat
      exposures. METHODS: A survey was administered to a convenience sample of adult
      guano miners, bat hunters, game wardens, and residents/personnel at Buddhist
      temples where mass bat roosting occurs. The questionnaire elicited information on
      demographics, experience with bat exposures, and rabies knowledge. Participants
      were also asked to describe actions they would take in response to a bat bite as
      well as actions for a bite from a potentially rabid animal. Bivariate analysis
      was used to compare responses between groups and multivariable logistic
      regression was used to explore factors independently associated with being bitten
      or scratched by a bat. FINDINGS: Of 106 people interviewed, 11 (10%) identified
      bats as a potential source of rabies. A history of a bat bite or scratch was
      reported by 29 (27%), and 38 (36%) stated either that they would do nothing or
      that they did not know what they would do in response to a bat bite. Guano miners
      were less likely than other groups to indicate animal bites as a mechanism of
      rabies transmission (68% vs. 90%, p=0.03) and were less likely to say they would
      respond appropriately to a bat bite or scratch (61% vs. 27%, p=0.003). Guano
      mining, bat hunting, and being in a bat cave or roost area more than 5 times a
      year were associated with history of a bat bite or scratch. CONCLUSIONS: These
      findings indicate the need for educational outreach to raise awareness of bat
      rabies, promote exposure prevention, and ensure appropriate health-seeking
      behaviors for bat-inflicted wounds, particularly among at-risk groups in
      Thailand.

PMID- 21738802
TI  - Unleashing "civilian power": a new American diplomacy through neglected tropical
      disease control, elimination, research, and development.

PMID- 21738804
TI  - Why is Plasmodium vivax a neglected tropical disease?

PMID- 21738803
TI  - SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human
      African trypanosomiasis.
AB  - BACKGROUND: Human African trypanosomiasis (HAT) is an important public health
      problem in sub-Saharan Africa, affecting hundreds of thousands of individuals. An
      urgent need exists for the discovery and development of new, safe, and effective
      drugs to treat HAT, as existing therapies suffer from poor safety profiles,
      difficult treatment regimens, limited effectiveness, and a high cost of goods. We
      have discovered and optimized a novel class of small-molecule boron-containing
      compounds, benzoxaboroles, to identify SCYX-7158 as an effective, safe and orally
      active treatment for HAT. METHODOLOGY/PRINCIPAL FINDINGS: A drug discovery
      project employing integrated biological screening, medicinal chemistry and
      pharmacokinetic characterization identified SCYX-7158 as an optimized analog, as
      it is active in vitro against relevant strains of Trypanosoma brucei, including
      T. b. rhodesiense and T. b. gambiense, is efficacious in both stage 1 and stage 2
      murine HAT models and has physicochemical and in vitro absorption, distribution,
      metabolism, elimination and toxicology (ADMET) properties consistent with the
      compound being orally available, metabolically stable and CNS permeable. In a
      murine stage 2 study, SCYX-7158 is effective orally at doses as low as 12.5 mg/kg
      (QD*7 days). In vivo pharmacokinetic characterization of SCYX-7158 demonstrates
      that the compound is highly bioavailable in rodents and non-human primates, has
      low intravenous plasma clearance and has a 24-h elimination half-life and a
      volume of distribution that indicate good tissue distribution. Most importantly,
      in rodents brain exposure of SCYX-7158 is high, with C(max) >10 ug/mL and AUC(0
      24 hr) >100 ug*h/mL following a 25 mg/kg oral dose. Furthermore, SCYX-7158
      readily distributes into cerebrospinal fluid to achieve therapeutically relevant
      concentrations in this compartment. CONCLUSIONS/SIGNIFICANCE: The biological and
      pharmacokinetic properties of SCYX-7158 suggest that this compound will be
      efficacious and safe to treat stage 2 HAT. SCYX-7158 has been selected to enter
      preclinical studies, with expected progression to phase 1 clinical trials in
      2011.

PMID- 21738805
TI  - The effect of egg embryonation on field-use of a hookworm benzimidazole
      sensitivity egg hatch assay in Yunnan Province, People's Republic of China.
AB  - BACKGROUND: Current efforts to control human soil-transmitted helminths (STHs)
      involve the periodic mass administration of benzimidazole drugs to school aged
      children and other at- risk groups. Given that high levels of resistance to these
      drugs have developed in roundworms of livestock, there is a need to monitor drug
      efficacy in human STHs. The current study aimed to evaluate an in vitro egg hatch
      assay for measuring the sensitivity of human hookworms to benzimidazole drugs in
      an isolated field setting in southern Yunnan province, People's Republic of
      China. METHODOLOGY/PRINCIPAL FINDINGS: Egg hatch assays were performed with
      hookworm (Necator americanus) eggs extracted from 37 stool samples received from
      local school-aged children. The mean IC(50) was 0.10 ug/ml thiabendazole (95%
      CIs: 0.09-0.12 ug/ml). Observation of the eggs immediately prior to assay set-up
      revealed that a small percentage had embryonated in some samples. Scoring of %
      embryonation of eggs prior to the assay allowed for corrections to be made to
      IC(50), IC(95) and IC(99) values. Examination of the data with and without this
      correction revealed that the embryonation of a small number of eggs did not
      affect IC(50) values, but did increase IC(95) and IC(99) values for some samples.
      CONCLUSIONS/SIGNIFICANCE: This study has highlighted the impact of egg
      embryonation on the use of benzimidazole drug sensitivity assays for human
      hookworms in field settings. Given the greater flexibility required in human
      stool collection procedures compared to livestock studies, we suggest that
      embryonation of some eggs may be an unavoidable issue in some human studies.
      Hence, it needs to be measured and accounted for when analysing dose response
      data, particularly for generation of IC(95) and IC(99) values. The protocols used
      in this study and our suggested measures for accounting for egg embryonation
      should have widespread application in monitoring benzimidazole sensitivity at
      field sites worldwide.

PMID- 21738806
TI  - Selective decrease of components of the creatine kinase system and ATP synthase
      complex in chronic Chagas disease cardiomyopathy.
AB  - BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory
      dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC
      occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin
      America. Heart failure is associated with impaired energy metabolism, which may
      be correlated to contractile dysfunction. We thus analyzed the myocardial gene
      and protein expression, as well as activity, of key mitochondrial enzymes related
      to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated
      (IDC) and ischemic (IC) cardiomyopathies. METHODOLOGY/PRINCIPAL FINDINGS:
      Myocardium homogenates from CCC (N=5), IC (N=5) and IDC (N=5) patients, as well
      as from heart donors (N=5) were analyzed for protein and mRNA expression of
      mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP
      synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total
      myocardial CK activity was also assessed. Protein levels of CKM and CK activity
      were reduced in all three cardiomyopathy groups. However, total CK activity, as
      well as ATP synthase alpha chain protein levels, were significantly lower in CCC
      samples than IC and IDC samples. CCC myocardium displayed selective reduction of
      protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP
      levels. CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may
      be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP
      synthase alpha levels is consistent with a decrease in myocardial ATP generation
      through oxidative phosphorylation. Together, these results suggest that the
      energetic deficit is more intense in the myocardium of CCC patients than in the
      other tested dilated cardiomyopathies.

PMID- 21738807
TI  - Developmental transcriptomic features of the carcinogenic liver fluke, Clonorchis
      sinensis.
AB  - Clonorchis sinensis is the causative agent of the life-threatening disease
      endemic to China, Korea, and Vietnam. It is estimated that about 15 million
      people are infected with this fluke. C. sinensis provokes inflammation,
      epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause
      cholangiocarcinoma in chronically infected individuals. Accumulation of a large
      amount of biological information about the adult stage of this liver fluke in
      recent years has advanced our understanding of the pathological interplay between
      this parasite and its hosts. However, no developmental gene expression profiles
      of C. sinensis have been published. In this study, we generated gene expression
      profiles of three developmental stages of C. sinensis by analyzing expressed
      sequence tags (ESTs). Complementary DNA libraries were constructed from the
      adult, metacercaria, and egg developmental stages of C. sinensis. A total of
      52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST
      sequences, and then these assemblies were further categorized into groups
      according to biological functions and developmental stages. Most of the genes
      that were differentially expressed in the different stages were consistent with
      the biological and physical features of the particular developmental stage; high
      energy metabolism, motility and reproduction genes were differentially expressed
      in adults, minimal metabolism and final host adaptation genes were differentially
      expressed in metacercariae, and embryonic genes were differentially expressed in
      eggs. The higher expression of glucose transporters, proteases, and antioxidant
      enzymes in the adults accounts for active uptake of nutrients and defense against
      host immune attacks. The types of ion channels present in C. sinensis are
      consistent with its parasitic nature and phylogenetic placement in the tree of
      life. We anticipate that the transcriptomic information on essential regulators
      of development, bile chemotaxis, and physico-metabolic pathways in C. sinensis
      that presented in this study will guide further studies to identify novel drug
      targets and diagnostic antigens.

PMID- 21738808
TI  - Evidence of gene conversion in genes encoding the Gal/GalNac lectin complex of
      Entamoeba.
AB  - The human gut parasite Entamoeba histolytica, uses a lectin complex on its cell
      surface to bind to mucin and to ligands on the intestinal epithelia. Binding to
      mucin is necessary for colonisation and binding to intestinal epithelia for
      invasion, therefore blocking this binding may protect against amoebiasis.
      Acquired protective immunity raised against the lectin complex should create a
      selection pressure to change the amino acid sequence of lectin genes in order to
      avoid future detection. We present evidence that gene conversion has occurred in
      lineages leading to E. histolytica strain HM1:IMSS and E. dispar strain SAW760.
      This evolutionary mechanism generates diversity and could contribute to immune
      evasion by the parasites.

PMID- 21738809
TI  - The geographic distribution of Loa loa in Africa: results of large-scale
      implementation of the Rapid Assessment Procedure for Loiasis (RAPLOA).
AB  - BACKGROUND: Loiasis is a major obstacle to ivermectin treatment for
      onchocerciasis control and lymphatic filariasis elimination in central Africa. In
      communities with a high level of loiasis endemicity, there is a significant risk
      of severe adverse reactions to ivermectin treatment. Information on the
      geographic distribution of loiasis in Africa is urgently needed but available
      information is limited. The African Programme for Onchocerciasis Control (APOC)
      undertook large scale mapping of loiasis in 11 potentially endemic countries
      using a rapid assessment procedure for loiasis (RAPLOA) that uses a simple
      questionnaire on the history of eye worm. METHODOLOGY/PRINCIPAL FINDINGS: RAPLOA
      surveys were done in a spatial sample of 4798 villages covering an area of
      2500*3000 km centred on the heartland of loiasis in Africa. The surveys showed
      high risk levels of loiasis in 10 countries where an estimated 14.4 million
      people live in high risk areas. There was a strong spatial correlation among
      RAPLOA data, and kriging was used to produce spatially smoothed contour maps of
      the interpolated prevalence of eye worm and the predictive probability that the
      prevalence exceeds 40%. CONCLUSION/SIGNIFICANCE: The contour map of eye worm
      prevalence provides the first global map of loiasis based on actual survey data.
      It shows a clear distribution with two zones of hyper endemicity, large areas
      that are free of loiasis and several borderline or intermediate zones. The
      surveys detected several previously unknown hyperendemic foci, clarified the
      distribution of loiasis in the Central African Republic and large parts of the
      Republic of Congo and the Democratic Republic of Congo for which hardly any
      information was available, and confirmed known loiasis foci. The new maps of the
      prevalence of eye worm and the probability that the prevalence exceeds the risk
      threshold of 40% provide critical information for ivermectin treatment programs
      among millions of people in Africa.

PMID- 21738810
TI  - Synergism between prior Anisakis simplex infections and intake of NSAIDs, on the
      risk of upper digestive bleeding: a case-control study.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      prior Anisakis infections and upper gastrointestinal bleeding (UGIB), and its
      interaction with non-steroidal anti-inflammatory drug (NSAID) intake.
      METHODS/PRINCIPAL FINDINGS: We conducted a hospital-based case-control study
      covering 215 UGIB cases and 650 controls. Odds ratios (ORs) with their confidence
      intervals (95% CIs) were calculated, as well as the ratio of the combined effects
      to the sum of the separate effects of Anisakis allergic sensitization and NSAIDs
      intake. Prior Anisakis infections were revealed by the presence of anti-Anisakis
      IgE antibodies specific to the recombinant Ani s 1 and Ani s 7 allergens used as
      the targets in indirect ELISA. Prior Anisakis infections (OR 1.74 [95% CI: 1.10
      to 2.75]) and the intake of NSAIDs (OR 6.63 [95% CI: 4.21 to 10.43]) increased
      the risk of bleeding. Simultaneous NSAIDs intake and Anisakis allergic
      sensitization increased the risk of UGIB 14-fold (OR=14.46 [95% CI: 6.08 to
      34.40]). This interaction was additive, with a synergistic index of 3.01 (95% CI:
      1.18-7.71). CONCLUSIONS: Prior Anisakis infection is an independent risk factor
      for UGIB, and the joint effect with NSAIDs is 3 times higher than the sum of
      their individual effects.

PMID- 21738811
TI  - Parasitic loads in tissues of mice infected with Trypanosoma cruzi and treated
      with AmBisome.
AB  - BACKGROUND: Chagas disease is one of the most important public health problems
      and a leading cause of cardiac failure in Latin America. The currently available
      drugs to treat T. cruzi infection (benznidazole and nifurtimox) are effective in
      humans when administered during months. AmBisome (liposomal amphotericin B),
      already shown efficient after administration for some days in human and
      experimental infection with Leishmania, has been scarcely studied in T. cruzi
      infection. AIMS: This work investigates the effect of AmBisome treatment,
      administered in 6 intraperitoneal injections at various times during acute and/or
      chronic phases of mouse T. cruzi infection, comparing survival rates and
      parasitic loads in several tissues. METHODOLOGY: Quantitative PCR was used to
      determine parasitic DNA amounts in tissues. Immunosuppressive treatment with
      cyclophosphamide was used to investigate residual infection in tissues. FINDINGS:
      Administration of AmBisome during the acute phase of infection prevented mice
      from fatal issue. Parasitaemias (microscopic examination) were reduced in acute
      phase and undetectable in chronic infection. Quantitative PCR analyses showed
      significant parasite load reductions in heart, liver, spleen, skeletal muscle and
      adipose tissues in acute as well as in chronic infection. An earlier
      administration of AmBisome (one day after parasite inoculation) had a better
      effect in reducing parasite loads in spleen and liver, whereas repetition of
      treatment in chronic phase enhanced the parasite load reduction in heart and
      liver. However, whatever the treatment schedule, cyclophosphamide injections
      boosted infection to parasite amounts comparable to those observed in acutely
      infected and untreated mice. CONCLUSIONS: Though AmBisome treatment fails to
      completely cure mice from T. cruzi infection, it impedes mortality and reduces
      significantly the parasitic loads in most tissues. Such a beneficial effect,
      obtained by administrating it over a short time, should stimulate studies on
      using AmBisome in association with other drugs in order to shorten recovery from
      T. cruzi infection.

PMID- 21738812
TI  - Contrasting population structures of two vectors of African trypanosomoses in
      Burkina Faso: consequences for control.
AB  - BACKGROUND: African animal trypanosomosis is a major obstacle to the development
      of more efficient and sustainable livestock production systems in West Africa.
      Riverine tsetse species such as Glossina palpalis gambiensis Vanderplank and
      Glossina tachinoides Westwood are the major vectors. A wide variety of control
      tactics is available to manage these vectors, but their removal will in most
      cases only be sustainable if the control effort is targeting an entire tsetse
      population within a circumscribed area. METHODOLOGY/PRINCIPAL FINDINGS: In the
      present study, genetic variation at microsatellite DNA loci was used to examine
      the population structure of G. p. gambiensis and G. tachinoides inhabiting four
      adjacent river basins in Burkina Faso, i.e. the Mouhoun, the Comoe, the Niger and
      the Sissili River Basins. Isolation by distance was significant for both species
      across river basins, and dispersal of G. tachinoides was ~3 times higher than
      that of G. p. gambiensis. Thus, the data presented indicate that no strong
      barriers to gene flow exists between riverine tsetse populations in adjacent
      river basins, especially so for G. tachinoides. CONCLUSIONS/SIGNIFICANCE:
      Therefore, potential re-invasion of flies from adjacent river basins will have to
      be prevented by establishing buffer zones between the Mouhoun and the other river
      basin(s), in the framework of the PATTEC (Pan African Tsetse and Trypanosomosis
      Eradication Campaign) eradication project that is presently targeting the
      northern part of the Mouhoun River Basin. We argue that these genetic analyses
      should always be part of the baseline data collection before any tsetse control
      project is initiated.

PMID- 21738813
TI  - Evidence for a peak shift in a humoral response to helminths: age profiles of IgE
      in the Shuar of Ecuador, the Tsimane of Bolivia, and the U.S. NHANES.
AB  - BACKGROUND: The peak shift model predicts that the age-profile of a pathogen's
      prevalence depends upon its transmission rate, peaking earlier in populations
      with higher transmission and declining as partial immunity is acquired. Helminth
      infections are associated with increased immunoglobulin E (IgE), which may convey
      partial immunity and influence the peak shift. Although studies have noted peak
      shifts in helminths, corresponding peak shifts in total IgE have not been
      investigated, nor has the age-patterning been carefully examined across
      populations. We test for differences in the age-patterning of IgE between two
      South American forager-horticulturalist populations and the United States: the
      Tsimane of Bolivia (n=832), the Shuar of Ecuador (n=289), and the U.S. NHANES
      (n=8,336). We then examine the relationship between total IgE and helminth
      prevalences in the Tsimane. METHODOLOGY/PRINCIPAL FINDINGS: Total IgE levels were
      assessed in serum and dried blood spots and age-patterns examined with non-linear
      regression models. Tsimane had the highest IgE (geometric mean =8,182 IU/ml),
      followed by Shuar (1,252 IU/ml), and NHANES (52 IU/ml). Consistent with
      predictions, higher population IgE was associated with steeper increases at early
      ages and earlier peaks: Tsimane IgE peaked at 7 years, Shuar at 10 years, and
      NHANES at 17 years. For Tsimane, the age-pattern was compared with fecal helminth
      prevalences. Overall, 57% had detectable eggs or larva, with hookworm (45.4%) and
      Ascaris lumbricoides (19.9%) the most prevalent. The peak in total IgE occurred
      around the peak in A. lumbricoides, which was associated with higher IgE in
      children <10, but with lower IgE in adolescents. CONCLUSIONS: The age-patterning
      suggests a peak shift in total IgE similar to that seen in helminth infections,
      particularly A. lumbricoides. This age-patterning may have implications for
      understanding the effects of helminths on other health outcomes, such as allergy,
      growth, and response to childhood vaccination.

PMID- 21738814
TI  - Mapping the global distribution of trachoma: why an updated atlas is needed.

PMID- 21738815
TI  - Vascular malformations and hemangiolymphangiomas of the gastrointestinal tract:
      morphological features and clinical impact.
AB  - PURPOSE: The purpose of our study was to describe the morphological features of
      gastrointestinal vascular malformations (VM) and of hemangiolymphangiomas (HLA)
      and to establish correlations with clinical characteristics. Significant
      findings: Fifteen VMs and 12 HLAs that were encountered over a period of 22
      years, were retrospectively analyzed. The VMs often involved the colon, small
      intestine, but also the stomach, whereas none of the HLAs arose in the stomach.
      VMs were more frequently associated with gastrointestinal bleeding, ulcer and
      were larger than HLAs (p<0.01 for all comparisons). Intralesional hemorrhage and
      thrombosis were associated with VM (p=0.02 and p=0.05). Surgical resection was
      performed for 1 HLA and 14 VMs. Vessel abnormalities such as shunt vessels, wall
      tufts (excrescences) and arterialized veins were more frequent in VMs (p=0.01,
      p=0.04 and <0.01, respectively) whereas aneurysm-like cavities were observed in
      both lesion types. Mucosal abnormal vessels were observed only in VMs, whereas
      HLAs were associated with mucosal lymphatic clusters (p<0.01). Most HLAs
      contained a D2-40 hetero-geneously positive lymphatic component, were Glut-1
      negative and CD31 reactive. There was no statistical difference in occurrence of
      associated autoimmune, tumoral and cardiovascular conditions between the two
      patient groups. CONCLUSIONS: The results of our study suggest that morphological
      features such as increased size, ulcer, thrombosis, hemorrhage and presence of
      aberrant mucosal vessels favor the diagnosis of VM. Co-existence of other
      clinical conditions such as cardiovascular disease, encountered in association
      with both lesion types, might exacerbate a tendency towards hemorrhage.

PMID- 21738816
TI  - The proliferation markers Ki-67/MIB-1, phosphohistone H3, and survivin may
      contribute in the identification of aggressive ovarian carcinomas.
AB  - The identification of new proliferation markers could have clinical implications
      in ovarian carcinoma by stratifying patients for treatment and follow-up. The aim
      of this study was to evaluate the diagnostic and prognostic value of the
      proliferation markers Ki-67/MIB-1, phosphorylated histone H3 (PHH3), and survivin
      in epithelial ovarian tumors. Ninety women with a pelvic mass who underwent
      surgery at the Department of Gynecological Oncology were included: 68 ovarian
      carcinomas, 11 borderline tumors, and 11 ovarian cystadenomas. We performed
      mitotic count and immunohistochemical analyses of Ki-67/MIB-1, PHH3, and
      survivin, related to clinicopathological parameters. Uni- and multivariate
      analyses of five-year overall survival were performed. We found statistically
      significant correlations between mitotic count, Ki-67/MIB-1, PHH3, and survivin.
      The expression of all proliferation markers was significantly higher in the
      carcinomas than in the borderline and benign tumors (p<0.05). There was, however
      an overlap of indices between the different malignancy groups. Women with
      advanced stage cancers (FIGO stage III and IV) had significantly higher tumor
      expression of all markers compared to patients with early stage cancers (FIGO
      stage I and II). Women with advanced disease and complete chemotherapy response
      had higher Ki67/MIB-1 expression than women without complete chemotherapy
      response. All markers had an impact on survival in the univariate analyses. In
      the multivariate analysis, however, only age and stage of disease reached
      statistical significance as prognostic factors. In conclusion, the proliferation
      markers Ki-67/MIB-1, PHH3, and survivin are positively correlated with each other
      and with tumor grade, and may contribute in the identification of aggressive
      ovarian carcinomas.

PMID- 21738817
TI  - Toponostics of invasive ductal breast carcinoma: combination of spatial protein
      expression imaging and quantitative proteome signature analysis.
AB  - Due to enormous advances in quantitative proteomics and in immunohistochemistry
      (pathology), the two research areas have now reached the state to be successfully
      interwoven in order to tackle challenges in toponostics and to open tumor
      targeted systems pathology approaches. In this study the differential expressions
      of candidate proteins nucleophosmin, nucleoside diphosphate kinase A/B (NDKA/B),
      osteoinducive factor (mimecan), and pyru-vate kinase M2 from a quantitative
      proteome signature for invasive ductal breast cancer were determined by
      immunohistochemistry on 53 tissue slices from formalin-fixed and paraffin
      embedded tumor and control tissue samples from ten patients and fourteen
      controls. In addition, 87 images from the Human Protein Atlas representing seven
      tumor and nine normal breast tissue samples were investigated by computer
      assisted semi-quantitative density measurements on nucleophosmin, nucleoside
      diphosphate kinase A/B (NDKA/B), osteoinducive factor (mimecan), pyruvate kinase
      M2, glyceraldehyde-3-phosphate dehydro-genase (GAP-DH), and mimecan
      (osteoinductive factor). Both IHC data sets match well to each other and support
      the quantitative proteome analysis data. Determining spatial distribution of
      signature protein expressions by protein imaging on morphologically intact tissue
      samples at the sub-cellular level and, hence, keeping all topological
      information, presents an added value to quantitative proteome data. Such
      comprehensive data sets are needed for both, pathway analyses and for "next
      generation clinical diagnostics" approaches.

PMID- 21738818
TI  - The value of second-opinion pathology diagnoses on prostate biopsies from
      patients referred for management of prostate cancer.
AB  - Gleason score (GS) (sum of primary plus secondary grades) is used to predict
      patients' clinical outcome and to customize treatment strategies for prostate
      cancer (PC). However, due in part to pathologist misreading, there is significant
      discrepancy of GS between needle-core biopsies (NCB) and radical prostatectomy
      specimens. We assessed the requirement for re-evaluating NCB diagnosed by outside
      pathologists in patients referred to our institution for management of PC. In 100
      patients, we reviewed both their original "outside" and second-opinion ("in
      house") diagnoses of the same NCB specimens, and compared them with the diagnoses
      of the whole-mount radical prostatectomy (WMRP) specimens (gold standard for
      analysis). We found that both outside and in-house biopsy GS vary significantly
      from the WMRP diagnoses, with GS undergrading substantially predominating above
      overgrading. Statistical analysis demonstrated that the main diagnostic
      discrepancy was in the differentiation between primary and secondary Gleason
      grades (mainly 3 and 4) and that outside NCB GS was significantly less accurate
      with respect to the WMRP specimens than the in-house NCB GS. In addition, in a
      different cohort of 65 NCB cases, we found that in 5 out of 11 patients, outside
      pathologists failed to report the presence of extraprostatic extension, an
      important feature for diagnosis of a higher pathology stage (pT3a). Since
      histopathological evaluation is a critical factor for appropriate treatment
      selection, we recommend that a re-evaluation by in-house urologic pathologists
      should be performed in all outside NCB specimens before patients are admitted for
      treatment in any given institution.

PMID- 21738819
TI  - Mammalian target of rapamycin: a central node of complex signaling cascades.
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that
      regulates cell growth and metabolism in response to diverse external stimuli. In
      the presence of mitogenic stimuli, mTOR transduces signals that activate the
      translational machinery and promote cell growth. mTOR functions as a central node
      in a complex net of signaling pathways that are involved both in normal
      physiological, as well as pathogenic events. mTOR signaling occurs in concert
      with upstream Akt and tuberous sclerosis complex (TSC) and several downstream
      effectors. During the past few decades, the mTOR-mediated pathway has been shown
      to promote tumorigenesis through the coordinated phosphorylation of proteins that
      directly regulate cell-cycle progression and metabolism, as well as transcription
      factors that regulate the expression of genes involved in the oncogenic
      processes. The importance of mTOR signaling in oncology is now widely accepted,
      and agents that selectively target mTOR have been developed as anti-cancer drugs.
      In this review, we highlight the past research on mTOR, including clinical and
      pathological analyses, and describe its molecular mechanisms of signaling, and
      its roles in the physiology and pathology of human diseases, particularly, lung
      carcinomas. We also discuss strategies that might lead to more effective clinical
      treatments of several diseases by targeting mTOR.

PMID- 21738820
TI  - rAAV-mediated delivery of brain-derived neurotrophic factor promotes neurite
      outgrowth and protects neurodegeneration in focal ischemic model.
AB  - Stroke is one of the neurological diseases which lead to permanently neuronal
      damage after temporary or long-term occlusion of vessels or after heart attack.
      However, there are few efficient strategies to prevent or treat this kind of
      insult in clinical because the consequence is irreversible and could be long
      lasting after the onset of stroke. Gene therapy especially using viral system has
      long been addressed to be of great potential to reduce the damage. Here, we
      generated recombinant adeno-associated virus (rAAV) carrying brain-derived
      neurotrophic factor (BDNF) gene. Cells infected with rAAV-BDNF could be able to
      produce functional BDNF which promoted neurite outgrowth and protected neurons
      from apoptosis induced by serum deprivation. Further more, single injection of
      rAAV showed neuroprotection against cell death in focal ischemic model. These
      results showed that rAAV-mediated gene delivery is functional, which shed light
      to the future application of viral system-based gene therapy in clinical.

PMID- 21738821
TI  - Quantitative analysis of p53 expression in human normal and cancer tissue
      microarray with global normalization method.
AB  - Tissue microarray based immunohistochemical staining and proteomics are important
      tools to create and validate clinically relevant cancer biomarkers.
      Immunohistochemical stains using formalin-fixed tissue microarray sections for
      protein expression are scored manually and semi-quantitatively. Digital image
      analysis methods remove some of the drawbacks of manual scoring but may need
      other methods such as normalization to provide across the board utility. In the
      present study, quantitative proteomics-based global normalization method was used
      to evaluate its utility in the analysis of p53 protein expression in mixed human
      normal and cancer tissue microarray. Global normalization used the mean or median
      of beta-actin to calculate ratios of individual core stain intensities, then log
      transformed the ratios, calculate a mean or median and subtracted the value from
      the log of ratios. In the absence of global normalization of p53 protein
      expression, 44% (42 of 95) of tissue cores were positive using the median of
      intensity values and 40% (38 of 95) using the mean of intensities as cut-off
      points. With global normalization, p53 positive cores changed to 20% (19 of 95)
      when using median of intensities and 15.8%(15 of 95) when the mean of intensities
      were used. In conclusion, the global normalization method helped to define
      positive p53 staining in the tissue microarray set used. The method used helped
      to define clear cut-off points and confirmed all negatively stained tissue cores.
      Such normalization methods should help to better define clinically useful
      biomarkers.

PMID- 21738822
TI  - Down-regulation of tTG expression by RNAi inhibits HSC proliferation and
      attenuates liver fibrosis.
AB  - PURPOSE: Expressed in hepatic stellate cell (HSC), tTG is involved in fibrotic
      diseases including human hepatic fibrosis by promoting the cross-linking of ECM
      and participating in the initiation and/or progression of liver fibrosis. The
      purpose of this study is to identify whether depletion of tTG could attenuate
      liver fibrosis. METHODS: In this study, primary hepatic stellate cells were
      isolated, purified, and cultured from rat. Expression of tTG gene was
      downregulated by lentivirus-mediated RNAi, and the effects on the activation,
      proliferation and apoptosis of HSC were investigated both in vitro and in vivo.
      RESULTS: Lentivirus-mediated RNAi successfully reduced the endogenous expression
      of tTG in cultured cells. The down-regulation of tTG markedly inhibited the
      proliferation of HSC and attenuated the synthesis of Collagen-1. The
      downregulation of tTG also markedly reduced the level of tTG and hydroxyproline
      induced by CCl(4) in rat livers at week 8 and week 12 after injection of CCl(4).
      CONCLUSIONS: In summary, tTG plays an important role in liver fibrosis.
      Lentivirus-mediated downregulation of tTG showed a potential anti-fibrosis effect
      in rats, providing new evidence that the involvement of tTG in HSC activation,
      also suggesting that RNAi-directed targeting of tTG may be used as a potent and
      specific therapeutic tool for the treatment of liver fibrosis, especially in
      inhibiting the activation of HSC.

PMID- 21738823
TI  - The role of E2F1 in the development of hypertrophic cardiomyopathy.
AB  - The overexpression of the transcription factor, E2F1, induces hypertrophy and
      apoptosis with cell cycle re-entry in cardiomyocytes in vitro and in vivo,
      suggesting that targeting E2F1 may have therapeutic potential. Accordingly, we
      tested the hypothesis that blocking the E2F1-mediated signal transduction pathway
      prevents cardiac hypertrophy by treating E2F1 knockout mice (E2F1-/-) with either
      isoproterenol (ISO) or Angiotensin II (ANG). Echocardi-ography was used to
      measure left ventricular mass index and myocardial performance index, a measure
      of combined systolic and diastolic left ventricular function. In control mice
      (E2F1+/+) both ISO and ANG treatments induced cardiac hypertrophy, and impaired
      ventricular function in ANG treated mice. In contrast to previously published
      work, E2F1-/- mice also demonstrated a similar pattern of cardiac hypertrophy and
      function after either treatment. Atrial natriuretic peptide, a molecular marker
      of hypertrophy and necropsy-determined body weight-normalized left ventricle mass
      were similarly increased in ISO and ANG treated E2F1+/+ and E2F-/- mice,
      supporting the echocardiographic data. These data indicate that E2F1 is not
      necessary for the development of cardiac hypertrophy although studies using an
      overexpression approach suggest a causal role of E2F1. The reason for this
      discrepancy is unclear, although it is possible that other E2F-family members
      (e.g., E2F2) may play a compensatory role. In conclusion, our data demonstrate
      that cardiac hypertrophy can be induced in an E2F1-independent fashion and
      suggest that in contrast to previous reports, targeting E2F1 may not be a good
      therapeutic approach.

PMID- 21738824
TI  - Subcorneal pustular dermatosis an immnohisto-pathological perspective.
AB  - Subcorneal pustular dermatosis (SPD) represents a chronic, relapsing sterile
      pustular eruption, involving the trunk and flexoral proximal extremities. A 54
      year-old female presented with recurrent, flaccid pustules measuring several
      millimeters in diameter, on normal and mildly erythematous skin of the groin and
      submammary areas. Biopsies for hematoxylin and eosin (H&E) examination, direct
      immunofluorescence (DIF) and immunohistochemistry (IHC) analysis were performed.
      The H&E staining demonstrated typical features of SPD, including some damage
      within dermal pilosebaceous units subjacent to the subcorneal blistering process.
      DIF revealed strong deposits of immunoreactants IgG, IgM, fibrinogen and
      complement/C3, present in a shaggy pattern within the subcorneal disease areas;
      in focal, areas of the basement membrane junction and in focal pericytoplasmic
      areas of epidermal keratinocytes. IHC revealed strong positivity to HLA-DPDQDR,
      mast cell tryptase, CD68, and ZAP-70 in the subcorneal inflammatory infiltrate,
      and surrounding dermal blood vessels. Myeloperoxidase was also positive. Positive
      staining with the anti-ribosomal protein S6-pS240 at the edges of hair follicles
      and sebaceous glands subjacent to the subcorneal blisters was also noted.
      CONCLUSIONS: We conclude that this disorder may have several components in its
      etiopathology, including a possible restricted immune response and a possible
      genetic component; these possibilities warrant further investigation.

PMID- 21738825
TI  - Dural-based metastatic carcinomas mimicking primary CNS neoplasia: report of 7
      cases emphasizing the role of timely surgery and accurate pathologic evaluation.
AB  - Clinical presentation with dural-based metastasis mimicking meningiomas is rare.
      We aimed to evaluate the role of frozen section in guiding surgery and
      histopathologic diagnosis in determining primary sites of dural-based metastatic
      carcinomas. Following the receipt of HAC approval, we retrospectively reviewed
      7cases presenting with dural-based masses clinically suspected to be primary
      brain tumors (6 meningiomas and 1 superficial glioblastoma), but diagnosed to be
      metastatic carcinomas on subsequent resection. Pertinent clinical records and
      follow-up data were reviewed. Patient's age ranged from 59 to 80 years. Imaging
      showed extra-axial dural-based masses with contiguous but not primary brain
      involvement. On intra-operative frozen section (not performed in case 7),
      differential diagnoses included metastatic carcinoma in all cases, and surgery
      modified accordingly. Nesting, cribriform, and "picket-fence" like glands were
      among useful histologic diagnostic patterns. Immunoprofile supported histologic
      diagnosis in all cases. Subsequent clinical and radiologic evaluation confirmed
      coexistent sites of origin in all cases. The metastases were solitary in all
      cases; except multiple dural-based tumors in case 1, in which interestingly no
      systemic metastasis were identified. Dural-based metastatic carcinomas mimicking
      meningiomas may be solitary, of unknown primary, or without concomitant systemic
      spread on imaging. Frozen section evaluation is helpful in modifying surgery.
      Although high-grade, these are typically differentiated enough to allow accurate
      histopathologic diagnosis, and reasonable determination of primary tumor site,
      especially with a judicious panel of cytokeratins, transcription factors, hormone
      receptors and relatively organ-specific markers. Clinicians and pathologists need
      to be aware of the occurrence, spectrum, need for timely intervention, and
      accurate diagnosis of dural-based metastatic carcinomas.

PMID- 21738826
TI  - Z-mammaplasty: a novel concept in mastopexy.
AB  - BACKGROUND: The inverted-T technique is the most popular skin pattern used for
      mastopexy, but short scar variations have increased in popularity over recent
      years. With respect to nipple elevation, superior, superomedial, medial,
      inferior, lateral, and central pedicle designs have been described. OBJECTIVES:
      We introduce a novel concept for mastopexy, the glandular Z-mammaplasty, and
      assess its anatomic and technical feasibility. METHODS: Glandular Z-plasty was
      performed on 15 human female cadavers. Various parameters were measured pre- and
      postoperatively to assess degree of ptosis and subsequently compared by student t
      test. RESULTS: Average pre and postoperative breast width (28.5 +/- 4.7 cm, 26.7
      +/- 3.2 cm, P = .009), breast length (25 +/- 6.6 cm and 21.8 +/- 4.3 cm P =
      .005), breast height (10.7 +/- 3.7 cm and 9.5 +/- 2.9 cm, P = .02), and ptosis
      degree (1.9 +/- 0.9 cm and 0.3 +/- 0.5 cm, P < .0001) were determined. Inferior
      limb transposition moved the nipple closer to the sternal notch and sternum
      midline an average of 5.3 +/- 2.2 cm and 2.4 +/- 1.7 cm, respectively. The
      average Z-plasty degree was 34.5 +/- 8.2 degrees . The average central limb
      length was 8.7 +/- 2.1, and the average pedicle width was 5.4 +/- 0.8 cm.
      Buttress support of the nipple was accomplished by caudal transposition of the
      superior Z-plasty flap and its inset below the nipple. CONCLUSION: We demonstrate
      that glandular Z-mammaplasty is indeed feasible. The grade of ptosis was
      statistically significantly improved, with the nipple moving superiorly an
      average of 5.3 cm in our study group.

PMID- 21738827
TI  - Chondromucosal nasal flap with the transposition flap of von langenbeck as a good
      election for the total lower eyelid defect reconstruction in an old patient with
      an elevated vision loss in the contralateral eye.
AB  - OBJECTIVE: The management of lower eyelid reconstruction has a variety of
      treatment strategies with varying success depending on the patient. We tried to
      apply the most suitable reconstruction techniques for this particular case.
      METHODS: We report a case of a 99-year-old woman, with a vision loss of 70% in
      the left eye and 40% in the right eye, who underwent basal cell carcinoma
      resection of the lower right eyelid 3 months before. The margins of resection and
      the deepest layers were affected. After the histopathology report, we decided to
      plan a more aggressive treatment with a total resection of the lower right
      eyelid. We had a case with 3 added difficulties: the old age of the patient, the
      vision loss in the contralateral eye, and the size of the resection. RESULTS: On
      the basis of our experience and the bibliography reviewed, we decided to use the
      chondromucosal nasal flap for the posterior lamella reconstruction and the
      transposition flap of von Langenbeck for the anterior lamella. We found it was a
      good election for this patient since we achieved good functional, anatomical, and
      aesthetical results with a one-step operation. CONCLUSIONS: The chondromucosal
      nasal flap with the transposition flap of von Langenbeck was a good election for
      a total lower eyelid defect reconstruction in an old patient with a high vision
      loss in the contralateral eye.

PMID- 21738828
TI  - LETTER TO THE EDITOR S-Plasty Method for Secondary Scar Revision After Flap
      Surgery.

PMID- 21738829
TI  - Reconstruction of cheek defects.

PMID- 21738830
TI  - Traversing the NPC along the pore membrane: targeting of membrane proteins to the
      INM.
AB  - The inner nuclear membrane (INM) accommodates a specific set of integral membrane
      proteins many of which interact with chromatin and/or in metazoan cells with the
      lamina network. The localization of these proteins characterizes this membrane
      area of the nuclear envelope (NE) despite the fact that the INM forms a membrane
      continuum with the outer nuclear membrane (ONM) and the remaining endoplasmic
      reticulum (ER). In fact, the INM can be regarded as a highly specialized membrane
      subdomain of the ER. How the specific protein composition of the INM is
      established and maintained and whether this is achieved via a single unifying
      mechanism is by and large unclear. Recent experiments shed light on some aspects
      of the process.

PMID- 21738831
TI  - New insights into the nuclear localization of retroviral Gag proteins.
AB  - Retroviruses assemble new virus particles that are released by budding from the
      plasma membranes of infected cells. Gag proteins, encoded by retroviruses,
      orchestrate the assembly of virus particles in close collaboration with host cell
      machinery. The earliest steps in retrovirus assembly-those immediately following
      synthesis of Gag on cytosolic ribosomes-are poorly understood. Rous sarcoma virus
      (RSV) offers a unique model system for dissecting these early steps because the
      RSV Gag protein undergoes transient nuclear trafficking prior to plasma membrane
      transport. Other Gag proteins, including those of human immunodeficiency virus
      (HIV), murine leukemia virus (MLV), foamy virus and retrotransposons in
      Schizosaccharomyces pombe and Drosophila, have also been detected in the nucleus,
      suggesting that nuclear trafficking of Gag proteins is a common property of
      retroviruses and retrotransposons. In addition to retroviruses, many structural
      proteins of unrelated viruses, including influenza M1, NEP and NP proteins,38
      Borna disease virus N and P proteins28,56 and coronavirus N protein,23,57 undergo
      nuclear localization and bind viral RNAs to form viral ribonuclear protein (RNP)
      complexes that are exported from the nucleus for packaging into virus particles.
      Similarly, nuclear trafficking of the RSV Gag protein is required for efficient
      encapsidation of the viral genomic RNA (gRNA) into assembling virus particles.19
      Recently, we reported that the viral RNA itself appears to be a key factor in
      controlling the nucleus/cytosol distribution of RSV Gag.22 Our data demonstrate
      that binding of RSV RNA to the Gag protein promotes Gag-CRM1-RanGTP binding,
      resulting in export of the retroviral RNP from the nucleus. We propose that
      association of the viral RNA induces a conformational change in Gag that reveals
      its nuclear export signal (NES) and prepares that complex for its journey to the
      plasma membrane for budding. This work challenges existing dogmas regarding the
      molecular basis of Gag-mediated selection of gRNA for packaging and may lead to
      novel paradigms for the mechanism of retroviral genome encapsidation.

PMID- 21738832
TI  - Structural dynamics of the cell nucleus: basis for morphology modulation of
      nuclear calcium signaling and gene transcription.
AB  - Neuronal morphology plays an essential role in signal processing in the brain.
      Individual neurons can undergo use-dependent changes in their shape and
      connectivity, which affects how intracellular processes are regulated and how
      signals are transferred from one cell to another in a neuronal network. Calcium
      is one of the most important intracellular second messengers regulating cellular
      morphologies and functions. In neurons, intracellular calcium levels are
      controlled by ion channels in the plasma membrane such as NMDA receptors
      (NMDARs), voltage-gated calcium channels (VGCCs) and certain alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by
      calcium exchange pathways between the cytosol and internal calcium stores
      including the endoplasmic reticulum and mitochondria. Synaptic activity and the
      subsequent opening of ligand and/or voltage-gated calcium channels can initiate
      cytosolic calcium transients which propagate towards the cell soma and enter the
      nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope.
      We recently described the discovery that in hippocampal neurons the morphology of
      the nucleus affects the calcium dynamics within the nucleus. Here we propose that
      nuclear infoldings determine whether a nucleus functions as an integrator or
      detector of oscillating calcium signals. We outline possible ties between nuclear
      mophology and transcriptional activity and discuss the importance of extending
      the approach to whole cell calcium signal modeling in order to understand synapse
      to-nucleus communication in healthy and dysfunctional neurons.

PMID- 21738833
TI  - Binding kinetics of human ISWI chromatin-remodelers to DNA repair sites elucidate
      their target location mechanism.
AB  - Chromatin remodelers translocate nucleosomes along the DNA chain in an ATP
      dependent manner. This catalytic activity is particularly important for DNA
      replication and repair since both processes require a significant amount of
      nucleosome translocations and assembly during DNA synthesis. Recently, we have
      studied the mobility and interactions of the human ISWI family chromatin
      remodelers Snf2H and Snf2L as well as Acf1, one of the non-catalytic subunits
      present in the ACF and CHRAC complexes of Snf2H. We proposed that these protein
      complexes identify their nucleosomal substrates via a continuous sampling
      mechanism. It rationalizes the relatively high nuclear mobility and abundance
      observed for all ISWI proteins in terms of fast target location. According to our
      model a certain type of ISWI complex visits a given nucleosome in the human
      genome on the timescale of several seconds to a few minutes. Here, we show that
      the ISWI proteins Snf2H, Snf2L as well as Acf1 accumulate at UV-induced DNA
      damage sites within tens of seconds and reach a plateau after a few minutes.
      These findings corroborate the predictions of the continuous sampling mechanism
      as an efficient way for targeting chromatin remodelers to sites in the genome
      that require their activity. In comparison to the mobility of PCNA (proliferating
      cell nuclear antigen) that also accumulates at DNA repair sites the specifics of
      substrate location by chromatin remodelers are further characterized.

PMID- 21738834
TI  - Nuclear size, nuclear pore number and cell cycle.
AB  - In eukaryotic cells, the nucleus is a complex and sophisticated organelle
      containing genomic DNA and supports essential cellular activities. Its surface
      contains many nuclear pore complexes (NPCs), channels for macromolecular
      transport between the cytoplasm and nucleus. It has been observed that the
      nuclear volume and the number of NPCs almost doubles during interphase in
      dividing cells, but the coordination of these events with the cell cycle was
      poorly understood, particularly in mammalian cells. Recently, we demonstrated
      that cyclin-dependent protein kinases (Cdks) control interphase NPC formation in
      dividing human cells. Cdks drive the very early step of NPC formation because Cdk
      inhibition suppressed the generation of "nascent pores," which are considered to
      be immature NPCs, and disturbed expression and localization of some nucleoporins.
      Cdk inhibition did not affect nuclear volume, suggesting that these two processes
      have distinct regulatory mechanisms in the cell cycle. The details of our
      experimental systems and finding are discussed in more depth. With new findings
      recently reported, we also discuss possible molecular mechanisms of interphase
      NPC formation.

PMID- 21738835
TI  - Shelterin complex and associated factors at human telomeres.
AB  - The processes regulating telomere function have major impacts on fundamental
      issues in human cancer biology. First, active telomere maintenance is almost
      always required for full oncogenic transformation of human cells, through
      cellular immortalization by endowment of an infinite replicative potential.
      Second, the attrition that telomeres undergo upon replication is responsible for
      the finite replicative life span of cells in culture, a process called
      senescence, which is of paramount importance for tumor suppression in vivo. The
      process of telomere-based senescence is intimately coupled to the induction of a
      DNA damage response emanating from telomeres, which can be elicited by both the
      ATM and ATR dependent pathways. At telomeres, the shelterin complex is
      constituted by a group of six proteins which assembles quantitatively along the
      telomere tract, and imparts both telomere maintenance and telomere protection.
      Shelterin is known to regulate the action of telomerase, and to prevent
      inappropriate DNA damage responses at chromosome ends, mostly through inhibition
      of ATM and ATR. The roles of shelterin have increasingly been associated with
      transient interactions with downstream factors that are not associated
      quantitatively or stably with telomeres. Here, some of the important known
      interactions between shelterin and these associated factors and their interplay
      to mediate telomere functions are reviewed.

PMID- 21738836
TI  - Trypanosoma cruzi DNA replication includes the sequential recruitment of pre
      replication and replication machineries close to nuclear periphery.
AB  - In eukaryotes, many nuclear processes are spatially compartmentalized.
      Previously, we have shown that in Trypanosoma cruzi, an early-divergent
      eukaryote, DNA replication occurs at the nuclear periphery where chromosomes
      remain constrained during the S phase of the cell cycle. We followed Orc1/Cdc6, a
      pre-replication machinery component and the proliferating cell nuclear antigen
      (PCNA), a component of replication machinery, during the cell cycle of this
      protozoon. We found that, at the G(1) stage, TcOrc1/Cdc6 and TcPCNA are dispersed
      throughout the nuclear space. During the G(1)/S transition, TcOrc1/Cdc6 migrates
      to a region close to nuclear periphery. At the onset of S phase, TcPCNA is loaded
      onto the DNA and remains constrained close to nuclear periphery. Finally, in
      G(2), mitosis and cytokinesis, TcOrc1/Cdc6 and TcPCNA are dispersed throughout
      the nuclear space. Based on these findings, we propose that DNA replication in T.
      cruzi is accomplished by the organization of functional machineries in a spatial
      temporal manner.

PMID- 21738837
TI  - H3.3 is deposited at centromeres in S phase as a placeholder for newly assembled
      CENP-A in G1 phase.
AB  - Centromeres are key regions of eukaryotic chromosomes that ensure proper
      chromosome segregation at cell division. In most eukaryotes, centromere identity
      is defined epigenetically by the presence of a centromeric histone H3 variant
      CenH3, called CENP-A in humans. How CENP-A is incorporated and reproducibly
      transmitted during the cell cycle is at the heart of this fundamental epigenetic
      mechanism. Centromeric DNA is replicated during S phase; however unlike
      replication-coupled assembly of canonical histones during S phase, newly
      synthesized CENP-A deposition at centromeres is restricted to a discrete time in
      late telophase/early G(1). These observations raise an important question: when
      'old' CENP-A nucleosomes are segregated at the replication fork, are the
      resulting 'gaps' maintained until the next G(1), or are they filled by H3
      nucleosomes during S phase and replaced by CENP-A in the following G(1)?
      Understanding such molecular mechanisms is important to reveal the
      composition/organization of centromeres in mitosis, when the kinetochore forms
      and functions. Here we investigate centromeric chromatin status during the cell
      cycle, using the SNAP-tag methodology to visualize old and new histones on
      extended chromatin fibers in human cells. Our results show that (1) both histone
      H3 variants H3.1 and H3.3 are deposited at centromeric domains in S phase and (2)
      there is reduced H3.3 (but not reduced H3.1) at centromeres in G(1) phase
      compared to S phase. These observations are consistent with a replacement model,
      where both H3.1 and H3.3 are deposited at centromeres in S phase and
      'placeholder' H3.3 is replaced with CENP-A in G(1).

PMID- 21738838
TI  - Medical school accreditation in Australia: Issues involved in assessing major
      changes and new programs.
AB  - The Australian Medical Council (AMC) is an independent company for quality
      assurance and quality improvement in medical education in Australia and New
      Zealand. Accreditation procedures for the 20 medical schools in these two
      countries are somewhat different for three different circumstances or stages of
      school development: existing medical schools, established courses undergoing
      major changes, and new schools. This paper will outline some issues involved in
      major changes to existing courses, and new medical school programs. Major changes
      have included change from a 6 year undergraduate course to a 5 year undergraduate
      course or 4 year graduate-entry course, introduction of a lateral graduate-entry
      stream, new domestic site of course delivery, offshore course delivery, joint
      program between two universities, and major change to curriculum. In the case of
      a major change assessment, accreditation of the new or revised course may be
      granted for a period up to two years after the full course has been implemented.
      In the assessment of proposals for introduction of new medical courses, six
      issues needing careful consideration have arisen: forward planning, academic
      staffing, adequate clinical experience, acceptable research program, adequacy of
      resources, postgraduate training program and employment.

PMID- 21738839
TI  - Should the clinical study on opioid-induced cough continue?

PMID- 21738840
TI  - Comparison of effect-site concentration of remifentanil for tracheal intubation
      with the lightwand and laryngoscopy during propofol target-controlled infusion.
AB  - BACKGROUND: Target-controlled infusion (TCI) of propofol and remifentanil can
      provide satisfactory intubating conditions without a neuromuscular blocking
      agent. We compared the effect-site concentration of remifentanil required for
      intubation with the lightwand and the Macintosh laryngoscope during propofol TCI
      without a neuromuscular blocking agent in adult patients. METHODS: Forty-nine
      patients were randomly assigned to the lightwand group (n = 25) or the direct
      laryngoscope group (n = 24). Anesthesia was induced by propofol TCI with an
      effect-site concentration of 5.4 ug/ml. Two minutes after start of propofol TCI,
      remifentanil was administered at the predetermined effect-site concentration. The
      effect-site concentration of remifentanil was determined using Dixon's up-and
      down method (0.5 ng/ml as a step size). The first patient in each group was
      tested at 4.5 ng/ml of remifentanil. Tracheal intubation was performed 2 min
      after the start of remifentanil TCI. Acceptable intubation was defined as an
      excellent or good intubating conditions. RESULTS: Using a modified Dixon's up and
      down method, the EC50 +/- SD of remifentanil in the lightwand and laryngoscope
      groups was 4.75 +/- 0.71 ng/ml and 5.08 +/- 0.52 ng/ml, respectively; there was
      no statistically significant difference between the groups (P = 0.373).
      CONCLUSIONS: The effect-site concentration of remifentanil for acceptable
      intubation with the lightwand and Macintosh laryngoscope in 50% of adults did not
      differ during propofol TCI without a neuromuscular blocking agent.

PMID- 21738841
TI  - Effect-site concentration of remifentanil for blunting hemodynamic responses to
      tracheal intubation using light wand during target controlled infusion-total
      intravenous anesthesia.
AB  - BACKGROUND: Transillumination using a light wand is an alternative type of
      laryngoscope used for tracheal intubation. There is little information available
      on the effect-site concentration of remifentanil required to control hemodynamic
      changes induced by tracheal intubation using the transillumination method during
      total IV anesthesia. We therefore conducted this study to determine the effect
      site concentration of remifentanil blunting hemodynamic responses after tracheal
      intubation in patients receiving propofol anesthesia. METHODS: We enrolled 26
      healthy adult patients (ASA physical status I-II), aged 16-67 scheduled for
      surgery within 2 hours. All patients received a target-controlled infusion of 4
      ug/ml propofol. The effect-site target-concentration of remifentanil of 5.0 ng/ml
      was chosen for the first patient. We used the Dixon's up-and-down sequential
      allocation method for determining the next remifentanil concentration. The time
      required for tracheal intubation was measured as the level of intubation
      stimulation. RESULTS: The average intubation time was 13.9 +/- 9.1 seconds. From
      the Dixon's method, the EC(50) of remifentanil blunting the hemodynamic response
      to tracheal intubation was 2.94 ng/ml. CONCLUSIONS: This study shows that effect
      site concentrations of remifentanil of 2.94 ng/ml is effective in blunting
      sympathetic responses to tracheal intubation in 50% of patients with normal
      airway anatomy when combined with a target controlled infusion of propofol (4
      ug/ml).

PMID- 21738842
TI  - Intravenous dexamethasone pretreatment reduces remifentanil induced cough.
AB  - BACKGROUND: Remifentanil infusion is commonly used for general anesthesia but
      reflex cough can occur after an intravenous (IV) infusion. This study was
      designed to examine the effect of IV-dexamethasone on remifentanil-induced cough
      (RIC). METHODS: One hundred thirty patients scheduled for elective surgery were
      randomly assigned into two groups that received by either 2 ml of IV 0.9% saline
      (Group C, n = 68) or 10 mg of dexamethasone (Group D, n = 62) 5 min before
      administration of remifentanil at a target effect-site concentration of 5 ng/ml.
      The incidence and severity of coughs of each patient were recorded. RESULTS: The
      overall incidence of cough was 6.5% (4/62 patients) in Group D and 26.5% (18/68
      patients) in the Group C (P = 0.002). The severity of cough observed was
      significantly different by dexamethasone pretreatment (P = 0.02) but there were
      no significant hemodynamic changes. CONCLUSIONS: Pretreatment with dexamethasone
      after IV administration was effective in suppressing the reflex cough induced by
      remifentanil infusion.

PMID- 21738843
TI  - The effects of magnesium pretreatment on reperfusion injury during living donor
      liver transplantation.
AB  - BACKGROUND: Ischemia reperfusion (IR) injury is a complex phenomenon that leads
      to organ dysfunction and causes primary liver failure following liver
      transplantation. We investigated whether an intravenous administration of
      magnesium before reperfusion can prevent or reduce IR injury. METHODS: Fifty-nine
      living donor liver transplant recipients were randomly assigned to an MG group (n
      = 31) or an NS group (n = 28). Each group was also divided in two groups based on
      the preoperative magnesium levels (normal: >= 0.70 mmol/L, low: < 0.70 mmol/L).
      The MG groups received 25 mg/kg of MgSO(4) mixed in 100 ml normal saline
      intravenously before reperfusion and the NS groups received an equal volume of
      normal saline. The levels of lactate, pH, arterial oxygen tension, and base
      excess were measured to assess reperfusion injury at five specific times, which
      were 10 min after the beginning of anhepatic phase, and 10, 30, 60 and 120 min
      after reperfusion. To evaluate postoperative organ function, the serum aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and
      creatinine levels were measured at preoperative day 1, postoperative day 1 and 5.
      RESULTS: The blood lactate levels were significantly lower at 10, 30, 60 and 120
      min after reperfusion in the MG groups compared to the NS groups. In addition,
      significantly higher blood lactate levels were observed in the NS group with
      preoperative hypomagnesemia than in MG groups. CONCLUSIONS: Magnesium
      administration before reperfusion of liver transplantation significantly reduces
      blood lactate levels. These findings suggest that magnesium treatment may have
      protective effects on IR injury during living donor liver transplantation.

PMID- 21738844
TI  - Postoperative nausea and vomiting after endoscopic thyroidectomy: total
      intravenous vs. balanced anesthesia.
AB  - BACKGROUND: Endoscopic thyroidectomy was recently introduced and has been rapidly
      accepted by surgeons and patients. The present study was conducted to estimate
      and compare the incidences of postoperative nausea and vomiting (PONV) after
      endoscopic thyroidectomy using two different anesthetic methods: sevoflurane
      based balanced anesthesia; total intravenous anesthesia (TIVA). METHODS: Ninety
      nine female patients that were scheduled to undergo elective endoscopic
      thyroidectomy under general anesthesia were enrolled. These patients were
      randomly allocated to receive sevoflurane based balanced anesthesia (BA group) or
      propofol-remifentanil anesthesia (TIVA group). PONV was evaluated using a 4-point
      Likert scale, and pain using a visual analogue scale (VAS; range 0 to 100) for 0
      2, 2-6, and 6-24 hours postoperatively. At 24 hours postoperatively, overall
      patient satisfaction regarding PONV and pain were recorded. RESULTS: The
      incidence of PONV was 14.6% in the TIVA group and 51.3% in the BA group. The
      incidence of nausea at 0-2 and 2-6 hours postoperatively was lower in the TIVA
      group than in the BA group (4.2% vs. 35.9%, 6.3% vs. 23.1%, respectively), but no
      between-group difference was observed at 6-24 hours postoperatively (8.3% vs.
      5.1%). Antiemetic usage at 0-2 and 2-6 hours was lower in the TIVA than the BA
      group (4.2% vs. 38.5%, 6.3% vs. 23.1%), but no between-group difference was
      observed for 6-24 hours (6.3% vs. 7.7%). There were no differences in pain or in
      patient satisfaction. CONCLUSIONS: After endoscopic thyroidectomy, total
      intravenous anesthesia with propofol-remifentanil is associated with less PONV
      during the early postoperative period (0-6 hours) than sevoflurane based balanced
      anesthesia.

PMID- 21738845
TI  - Effects of 10% lidocaine spray on arterial pressure increase due to suspension
      laryngoscopy and cough during extubation.
AB  - BACKGROUND: It is well known that suspension laryngoscopy (SL) produces marked
      hemodynamic changes. Coughing during extubation sometimes causes adverse clinical
      problems. We investigated whether 10% lidocaine spray could attenuate hemodynamic
      stress responses due to SL and reduce coughing incidence during extubation.
      METHODS: Sixty patients undergoing SL were randomly divided into two groups and
      intubated without 10% lidocaine spray (control group) or given 1.5 mg/kg of 10%
      lidocaine, sprayed onto laryngeal and intratracheal sites 2 min prior to
      intubation (10% lidocaine group). Mean arterial pressure (MAP) and heart rates
      (HR) during SL and coughing incidence during extubation were recorded. RESULTS:
      MAP at 2.5 and 5 min (P < 0.05) and HR at 2.5 min after SL (P < 0.01) were
      greater in the control group than in the 10% lidocaine group. The number of
      coughs decreased in the 10% lidocaine group compared to the control group during
      pre- (6.8 +/- 3.2 vs 10.3 +/- 4.4, P < 0.01) and post-extubation period of 5 min
      (4.0 +/- 2.3 vs 6.2 +/- 4.2, P < 0.05) and during the entire study period (10.8
      +/- 3.9 vs 16.5 +/- 5.6, P < 0.001). CONCLUSIONS: Preoperative laryngeal and
      intratracheal spraying with 1.5 mg/kg of 10% lidocaine spray is effective for
      attenuation of arterial pressure increase to SL and suppression of coughing
      during extubation.

PMID- 21738846
TI  - Dexmedetomidine does not produce vasocontraction on human isolated gastroepiploic
      artery.
AB  - BACKGROUND: Recently, the addition of dexmedetomidine to sedation regimens after
      cardiac surgery had been reported and there is a possibility that dexmedetomidine
      can cause vasoconstriction. Vasopressin has been used as a prophylactic treatment
      for refractory vasodilatory shock during coronary artery bypass graft (CABG).
      Also, vasopressin may play an important role in initiating spasms at the graft
      artery. Here we evaluate the direct effect of dexmedetomidine on isolated human
      gastroepiploic arteries and the synergistic effect of dexmedetomidine and
      vasopressin. METHODS: Discarded gastroepiploic arteries from elective subtotal
      gastrectomy (n = 10) were used in this study. We measured the level of
      contraction in isolated human gastroepiploic arteries induced by increasing
      concentrations of dexmedetomidine (10(-10) to 10(-6) M) with or without
      vasopressin (10(-10), 10(-9) M). Arterial contractions caused by increasing
      concentrations of vasopressin (10(-10) to 10(-7.5) M) with or without
      dexmedetomidine (10(-9), 10(-7) M) were also measured in the tissue samples.
      RESULTS: Supraclinical concentrations of dexmedetomidine elicited contractions at
      concentrations of 10(-7) M and 10(-6) M (P < 0.05 versus resting tension). The
      same concentrations of dexmedetomidine (10(-7), 10(-6) M) significantly enhanced
      vasopressin-induced contractions (P < 0.05 versus vasopressin-induced
      contraction). Vasopressin produced concentration-dependent contractions and
      vasopressin (10(-10), 10(-9.5), 10(-9) M) also increased the intensity of
      dexmedetomidine (10(-7) M) induced contractions. CONCLUSIONS: There was a
      synergistic effect between supraclinical doses of dexmedetomidine and vasopressin
      on the degree of contraction in isolated human gastroepiploic arteries. However,
      a sedative dose of dexmedetomidine (clinical dose: 0.2-0.7 ug/kg/hr, plasma
      concentration: 0.36-1.25 ng/ml) did not enhance vasopressin induced-contraction
      in isolated human gastroepiploic arteries.

PMID- 21738847
TI  - Difficult tracheostomy tube placement in an obese patient with a short neck -A
      case report-.
AB  - We report a difficult case of tracheostomy in a 34-year-old obese woman with a
      short neck. The tracheostomy tube placement repeatedly failed because of
      anatomical changes due to obesity and a short neck, tracheal mucosal swelling due
      to prolonged intubation, and unexpected false passage; however, it was
      successfully performed using an endotracheal tube exchanger as a guidewire.

PMID- 21738848
TI  - Unexpected difficulty in ventilating the lungs after tracheal intubation -A case
      report-.
AB  - We experienced difficulty in ventilating the lungs of a patient after tracheal
      intubation. After intubation, an insufficient amount of tidal volume (V(T)) was
      delivered to the patient and the fiberoptic bronchoscopic examination identified
      partial abutment of the endotracheal tube (ETT) orifice against the tracheal
      wall. After various attempts to correctly place the ETT, a double-lumen
      endotracheal tube was placed to achieve a sufficient V(T). It is important to
      notice that even an appropriately placed ETT may get obstructed due to the left
      sided bevel at its tip.

PMID- 21738849
TI  - Extreme hyponatremia with moderate metabolic acidosis during hysteroscopic
      myomectomy -A case report-.
AB  - Excess absorption of fluid distention media remains an unpredictable complication
      of operative hysteroscopy and may lead to lethal conditions. We report an extreme
      hyponatremia, caused by using an electrolyte-free 5 : 1 sorbitol/mannitol
      solution as distention/irrigation fluid for hysteroscopic myomectomy. A 34-year
      old female developed severe pulmonary edema and extreme hyponatremia (83 mmol/L)
      during transcervical endoscopic myomectomy. A brain computed tomography showed
      mild brain swelling without pontine myelinolysis. The patient almost fully
      recovered in two days. Meticulous attention should be paid to intraoperative
      massive absorption of fluid distention media, even during a simple hysteroscopic
      procedure.

PMID- 21738850
TI  - Anesthetic management of non-cardiac surgery with adult onset type of cor
      triatriatum sinister -A case report-.
AB  - A 45-year-old woman with cor triatriatum sinister was admitted for laparoscopic
      resection of an ovarian tumor. Her medical history was benign with the exception
      of a single episode of syncope one year ago. A 1.5-cm membrane fenestration was
      found on echocardiography, but there were no other cardiac structural anomalies.
      General anesthesia was established with etomidate, sevoflurane, and remifentanil;
      no notable events occurred during the anesthesia. As cor triatriatum shows a
      clinical picture of mitral stenosis (MS), careful anesthetic management is
      required.

PMID- 21738851
TI  - Aspiration pneumonia in the child with DiGeorge syndrome -A case report-.
AB  - DiGeorge syndrome is associated with a chromosome 22q11.2 deletion and manifests
      with variable clinical findings. Aspiration pneumonia can be a perioperative
      complication of great concern in this syndrome. In this report, we present a case
      of a 16-month old child with DiGeorge syndrome undergoing cranioplasty. He
      developed perioperative aspiration pneumonia but was managed successfully.

PMID- 21738852
TI  - DNA methylation in thyroid tumorigenesis.
AB  - Thyroid cancer is the most common endocrine cancer with 1,690 deaths each year.
      There are four main types of which the papillary and follicular types together
      account for >90% followed by medullary cancers with 3% to 5% and anaplastic
      carcinomas making up <3%. Epigenetic events of DNA hypermethylation are emerging
      as promising molecular targets for cancer detection. Our immediate and long term
      goal is to identify DNA methylation markers for early detection of thyroid
      cancer. This pilot study comprised of 21 patients to include 11 papillary thyroid
      cancers (PTC), 2 follicular thyroid cancers (FTC), 5 normal thyroid cases, and 3
      hyperthyroid cases. Aberrant promoter methylation was examined in 24 tumor
      suppressor genes using the methylation specific multiplex ligation-dependent
      probe amplification (MS-MLPA) assay and in the NIS gene using methylation
      specific PCR (MSP). The frequently methylated genes were CASP8 (17/21), RASSF1
      (16/21) and NIS (9/21). In the normal samples, CASP8, RASSF1 and NIS were
      methylated in 5/5, 4/5 and 1/5 respectively. In the hyperthyroid samples, CASP8,
      RASSF1 and NIS were methylated in 3/3, 2/3 and 1/3 respectively. In the thyroid
      cancers, CASP8, RASSF1, and NIS were methylated in 9/13, 10/13, and 7/13
      respectively. CASP8, RASSF1 and NIS were also methylated in concurrently present
      normal thyroid tissue in 3/11, 4/11 and 3/11 matched thyroid cancer cases
      (matched for presence of both normal thyroid tissue and thyroid cancer),
      respectively. Our data suggests that aberrant methylation of CASP8, RASSF1, and
      NIS maybe an early change in thyroid tumorigenesis regardless of cell type. 

PMID- 21738853
TI  - Heart failure.

PMID- 21738854
TI  - Surgical treatment of atrial fibrillation: a review.
AB  - Atrial fibrillation is the most commonly sustained arrhythmia in man. While it
      affects millions of patients worldwide, its incidence will markedly increase with
      an aging population. Primary goals of AF therapy are to (1) reduce embolic
      complications, particularly stroke, (2) alleviate symptoms, and (3) prevent long
      term heart remodelling. These have been proven to be a challenge as there are
      major limitations in our knowledge of the pathological and electrophysiological
      mechanisms underlying AF. Although advances continue to be made in the medical
      management of this condition, pharmacotherapy is often unsuccessful. Because of
      the high recurrence rate of AF despite antiarrhythmic drug therapy for
      maintenance of sinus rhythm and the adverse effects of these drugs, there has
      been growing interest in nonpharmacological strategies. Surgery for treatment of
      AF has been around for some time. The Cox-Maze procedure is the gold standard for
      the surgical treatment of atrial fibrillation and has more than 90% success in
      eliminating atrial fibrillation. Although the cut and sew maze is very effective,
      it has been superseded by newer operations that rely on alternate energy sources
      to create lines of conduction block. In addition, the evolution of improved
      ablation technology and instrumentation has facilitated the development of
      minimally invasive approaches. In this paper, the rationale for surgical ablation
      for atrial fibrillation and the different surgical techniques that were developed
      will be explored. In addition, it will detail the new approaches to surgical
      ablation of atrial fibrillation that employ alternate energy sources.

PMID- 21738855
TI  - Possible association of high urinary magnesium and taurine to creatinine ratios
      with metabolic syndrome risk reduction in Australian aboriginals.
AB  - Background. Because of the epidemic of metabolic syndrome (MS) in Australian
      Aboriginals known for their higher cardiovascular mortality and shorter life
      expectancy, we analyzed the possible relationship of their MS risks with the
      current dietary custom. Methods. The subjects were 84 people aged 16-79 years.
      The health examination was conducted according to the basic protocol of WHO
      CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study. Results. The
      highest prevalence among MS risks was abdominal obesity (over 60%). After
      controlling for age and sex, the odds of obesity decreased significantly with
      high level of urinary magnesium/creatinine ratio (Mg/cre) (OR, 0.11; 95% CI, 0.02
      0.57; P < .05). The significant inverse associations of fat intake with Mg/cre
      and of fast food intake with urinary taurine/creatinine ratio were revealed.
      Conclusions. The high prevalence of obesity in the Aboriginal people of this area
      may partly be due to the reduction of beneficial nutrients intake including Mg
      and taurine.

PMID- 21738856
TI  - Surveillance of pediatric cardiac surgical outcome using risk stratifications at
      a tertiary care center in Thailand.
AB  - Objectives. To determine in-hospital mortality and complications of cardiac
      surgery in pediatric patients and identify predictors of hospital mortality.
      Methods. Records of pediatric patients who had undergone cardiac surgery in 2005
      were reviewed retrospectively. The risk adjustment for congenital heart surgery
      (RACHS-1) method, the Aristotle basic complexity score (ABC score), and the
      Society of Thoracic Surgeons and the European Association for Cardiothoracic
      Surgery Mortality score (STS-EACTS score) were used as measures. Potential
      predictors were analyzed by risk analysis. Results. 230 pediatric patients had
      undergone congenital cardiac surgery. Overall, the mortality discharge was 6.1%.
      From the ROC curve of the RACHS-1, the ABC level, and the STS-EACTS categories,
      the validities were determined to be 0.78, 0.74, and 0.67, respectively.
      Mortality risks were found at the high complexity levels of the three tools,
      bypass time >85 min, and cross clamp time >60 min. Common morbidities were
      postoperative pyrexia, bleeding, and pleural effusion. Conclusions. Overall
      mortality and morbidities were 6.1%. The RACHS-1 method, ABC score, and STS-EACTS
      score were helpful for risk stratification.

PMID- 21738857
TI  - Ibutilide for the Cardioversion of Paroxysmal Atrial Fibrillation during
      Radiofrequency Ablation of Supraventricular Tachycardias.
AB  - Direct current electrical cardioversion (DC-ECV) is the preferred treatment for
      the termination of paroxysmal atrial fibrillation (AF) that occurs during
      radiofrequency ablation (RFA) of supraventricular tachycardias (SVT). Intravenous
      Ibutilide may be an alternative option in this setting. Thirty-four out of 386
      patients who underwent SVT-RFA presented paroxysmal AF during the procedure and
      were randomized into receiving ibutilide or DC-ECV. Ibutilide infusion
      successfully cardioverted 16 out of 17 patients (94%) within 17.37 +/- 7.87  min.
      DC-ECV was successful in all patients (100%) within 17.29 +/- 3.04  min. Efficacy
      and total time to cardioversion did not differ between the study groups. No
      adverse events were observed. RFA was successfully performed in 16 patients (94%)
      in the ibutilide arm and in all patients (100%) in the DC-ECV arm, p = NS. In
      conclusion, ibutilide is a safe and effective alternative treatment for restoring
      sinus rhythm in cases of paroxysmal AF complicating SVT-RFA.

PMID- 21738858
TI  - Health-Adjusted Life Expectancy among Canadian Adults with and without
      Hypertension.
AB  - Hypertension can lead to cardiovascular diseases and other chronic conditions.
      While the impact of hypertension on premature death and life expectancy has been
      published, the impact on health-adjusted life expectancy has not, and constitutes
      the research objective of this study. Health-adjusted life expectancy (HALE) is
      the number of expected years of life equivalent to years lived in full health.
      Data were obtained from the Canadian Chronic Disease Surveillance System
      (mortality data 2004-2006) and the Canadian Community Health Survey (Health
      Utilities Index data 2000-2005) for people with and without hypertension. Life
      table analysis was applied to calculate life expectancy and health-adjusted life
      expectancy and their confidence intervals. Our results show that for Canadians 20
      years of age, without hypertension, life expectancy is 65.4 years and 61.0 years,
      for females and males, respectively. HALE is 55.0 years and 52.8 years for the
      two sexes at age 20; and 24.7 years and 22.9 years at age 55. For Canadians with
      hypertension, HALE is only 48.9 years and 47.1 years for the two sexes at age 20;
      and 22.7 years and 20.2 years at age 55. Hypertension is associated with a
      significant loss in health-adjusted life expectancy compared to life expectancy.

PMID- 21738859
TI  - Histologically measured cardiomyocyte hypertrophy correlates with body height as
      strongly as with body mass index.
AB  - Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH).
      This study correlates histologically measured myocytes with lean and fat body
      mass. Cases of LVH without coronary heart disease and normal controls came from
      forensic autopsies. The cross-sectional widths of myocytes in H&E-stained
      paraffin sections followed log normal distributions almost to perfection in all
      104 specimens, with constant coefficient of variation across the full range of
      ventricular weight, as expected if myocytes of all sizes contribute
      proportionately to hypertrophy. Myocyte sizes increased with height. By
      regression analysis, height(2.7) as a proxy for lean body mass and body mass
      index (BMI) as a proxy for fat body mass, exerted equal effects in the multiple
      correlation with myocyte volume, and the equation rejected race and sex. In
      summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass
      may contribute equally.

PMID- 21738860
TI  - The Prevalence of Undiagnosed HIV Infection in Those Who Decline HIV Screening in
      an Urban Emergency Department.
AB  - Objective. To determine the prevalence of occult HIV infection in patients who
      decline routine HIV testing in an urban emergency department. Design, Setting,
      and Patients. Discarded blood samples were obtained from patients who had
      declined routine ED HIV testing. After insuring that the samples came from
      patients not known to be HIV positive, they were deidentified, and rapid HIV
      testing was preformed using 5 MUL of whole blood. Main Outcome Measures. The
      prevalence of occult HIV infection in those who declined testing compared with
      prevalence in those who accepted testing. Results. 600 consecutive samples of
      patients who declined routine HIV screening were screened for HIV. Twelve (2%)
      were reactive. Over the same period of time, 4845 patients accepted routine HIV
      testing. Of these, 35 (0.7%) were reactive. The difference in the prevalence of
      HIV infection between those who declined and those who accepted testing was
      significant (P = .001). The relative risk of undetected HIV infection in the
      group that declined testing was 2.74 times higher (95% CI 1.44-5.18) compared
      with those accepted testing. Conclusion. The rate of occult HIV infection is
      nearly three-times higher in those who decline routine ED HIV testing compared
      with those who accept such testing. Interventions are urgently needed to decrease
      the opt-out rate in routine ED HIV testing settings.

PMID- 21738861
TI  - Time to and Predictors of CD4+ T-Lymphocytes Recovery in HIV-Infected Children
      Initiating Highly Active Antiretroviral Therapy in Ghana.
AB  - Background. CD4+ T-lymphocyte monitoring is not routinely available in most
      resource-limited settings. We investigated predictors of time to CD4+ T
      lymphocyte recovery in HIV-infected children on highly active antiretroviral
      (HAART) at Korle-Bu Teaching Hospital, Ghana. Methods. Time to CD4+ T-lymphocyte
      recovery was defined as achieving percent CD4+ T-lymphocytes of 25%. We used Cox
      proportional hazard models for identifying significant predictor variables.
      Results. Of the 233 children with complete CD4+ T-lymphocyte data, the mean age
      at HAART initiation was 5.5 (SD = 3.1) years. The median recovery time was 60
      weeks (95% CL: 55-65). Evidence at baseline of severe suppression in CD4+ T
      lymphocyte count adjusted for age, age at HAART initiation, gender, and having
      parents alive were statistically significant in predicting time to CD4+ T
      lymphocyte recovery. Conclusions. A targeted approach based on predictors of CD4+
      T-lymphocyte recovery can be a viable and cost-effective way of monitoring HAART
      in HIV-infected children in resource-limited settings.

PMID- 21738862
TI  - Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of
      26,387 MUg/L.
AB  - Serum ferritin rises in the anemia of chronic inflammation reflecting increased
      iron storage and other changes mediated by inflammation. When iron deficiency
      coexists, the ferritin may not always decline into the subnormal range. We
      describe the rare interaction of iron deficiency with the extreme
      hyperferritinemia characteristic of adult onset Still's disease. The combination
      has clinical relevance and allows deductions about the presence of serum ferritin
      at 26,387 MUg/L despite obvious iron depletion. The diagnosis of iron deficiency
      anemia was delayed and became fully obvious when her Still's disease remitted and
      serum ferritin decreased to 6.5 MUg/L. The coexistence of iron deficiency should
      be considered when evaluating a patient with anemia of chronic inflammation even
      when the ferritin level is elevated several hundredfold. Further insights on
      ferritin metabolism in Still's disease are suggested by the likelihood that the
      patient's massive hyperferritinemia in the acute phase of Still's disease was
      almost entirely of the iron-free apoferritin form.

PMID- 21738864
TI  - The management of iron chelation therapy: preliminary data from a national
      registry of thalassaemic patients.
AB  - Thalassaemia and other haemoglobinopathies constitute an important health problem
      in Mediterranean countries, placing a tremendous emotional, psychological, and
      economic burden on their National Health systems. The development of new
      chelators in the most recent years had a major impact on the treatment of
      thalassaemia and on the quality of life of thalassaemic patients. A new
      initiative was promoted by the Italian Ministry of Health, establishing a
      Registry for thalassaemic patients to serve as a tool for the development of cost
      effective diagnostic and therapeutic approaches and for the definition of
      guidelines supporting the most appropriate management of the iron-chelating
      therapy and a correct use of the available iron-chelating agents. This study
      represents the analysis of the preliminary data collected for the evaluation of
      current status of the iron chelation practice in the Italian thalassaemic
      population and describes how therapeutic interventions can widely differ in the
      different patients' age groups.

PMID- 21738863
TI  - Iron deficiency anemia: focus on infectious diseases in lesser developed
      countries.
AB  - Iron deficiency anemia is thought to affect the health of more than one billion
      people worldwide, with the greatest burden of disease experienced in lesser
      developed countries, particularly women of reproductive age and children. This
      greater disease burden is due to both nutritional and infectious etiologies.
      Individuals in lesser developed countries have diets that are much lower in iron,
      less access to multivitamins for young children and pregnant women, and increased
      rates of fertility which increase demands for iron through the life course.
      Infectious diseases, particularly parasitic diseases, also lead to both
      extracorporeal iron loss and anemia of inflammation, which decreases
      bioavailability of iron to host tissues. This paper will address the unique
      etiologies and consequences of both iron deficiency anemia and the alterations in
      iron absorption and distribution seen in the context of anemia of inflammation.
      Implications for diagnosis and treatment in this unique context will also be
      discussed.

PMID- 21738865
TI  - The strategy of combining antidepressants in the treatment of major depression:
      clinical experience in spanish outpatients.
AB  - Introduction. The combination of antidepressants is a useful tool in the
      treatment of major depression, especially in cases where there is a partial
      response to antidepressant monotherapy. However, the use of this strategy is a
      matter of controversy, and its frequency of use in clinical practice is not
      clear. The aim of our study is to assess the use of antidepressants combination
      in Spain by reviewing three databases used between 1997 and 2001. Methods.
      Databases pertain to patients who are study subjects of major depression
      treatment. These databases are a result of studies performed in Spain and in
      which 550 psychiatrists participated. The total studied sample was comprised of N
      = 2, 842 patients, aged over 18, fitting DSM-IV criteria for Major Depressive
      Episode. The percentage of patients who received more than one antidepressant and
      the types of combinations used was described. Subsequently, a comparative study
      between the group which received a combination of antidepressants (N = 64) and
      the group which received antidepressant monotherapy (N = 775) was performed.
      Results. 27.1% of patients were on antidepressive monotherapy treatment, and 2.2%
      were on combination therapy. In the comparison of patients on combination therapy
      and monotherapy, there were significant differences only in episode duration (P =
      0.001). The most frequent combinations are SSRIs and tricyclic antidepressants.
      The active principle most widely combined is fluoxetine. Conclusions. The
      prevalence of use of antidepressant combination therapy is 2.2% of the global
      sample and 8.3% of treated patients. Other than duration of the depressive
      episode, no clinical characteristics exclusive to patients who received
      combination rather than monotherapy were found. Our study found that the most
      frequent combination is SSRIs + TCAs, also being the most studied.

PMID- 21738866
TI  - Differences in Characteristics and Treatment Received among Depressed Adolescent
      Psychiatric Outpatients with and without Co-Occuring Alcohol Misuse: A 1-Year
      Follow-Up Study.
AB  - Objectives. We aimed at examining the differences between depressed psychiatric
      adolescent outpatients with and without cooccurring alcohol misuse in
      psychosocial background, clinical characteristics, and treatment received during
      one-year followup. Furthermore, we investigated factors related to nonattendance
      at treatment. Materials and Methods. Consecutive 156 adolescent (13-19 years)
      psychiatric outpatients with a unipolar depressive disorder at baseline were
      interviewed using structured measures at baseline and at 12 months. Alcohol
      misuse was defined as having an AUDIT score of 8 or more points. The outpatients
      received "treatment as usual" of clinically defined duration. Results. Among
      depressive outpatients, poor parental support, parental alcohol use and decreased
      attendance at treatment associated with alcohol misuse. The severity of alcohol
      use as measured by AUDIT-score was the strongest factor independently predicting
      nonattendance at treatment in multivariate analysis. Conclusions. Alcohol misuse
      indicates family problems, has a deleterious effect on treatment attendance, and
      should be taken into account when managing treatment for depressive adolescent
      outpatients.

PMID- 21738867
TI  - Depression and self-concept: personality traits or coping styles in reaction to
      school retention of Hispanic adolescents.
AB  - The purpose of this study was to investigate whether depression and self-concept
      could be construed as personality characteristics and/or coping styles in
      reaction to school retention or being held back a grade. The participants in this
      study were 156 urban Hispanic adolescents, ages 12-18, and of these, 51 or 33%
      had been retained in school. Students who had been retained reported a lower self
      concept score, higher GPA, and higher rates of depression, and they were more
      likely to be male than students who had not been retained. The findings of this
      study indicated that self-concept was a personality characteristic that, due to
      its malleability, is also a coping style in regards to retention with this
      Hispanic adolescent population.

PMID- 21738868
TI  - Improving the management of late-life depression in primary care: barriers and
      facilitators.
AB  - The objectives of this study were to elicit Canadian health professionals' views
      on the barriers to identifying and treating late-life depression in primary care
      settings and on the solutions felt to be most important and feasible to
      implement. A consensus development process was used to generate, rank, and
      discuss solutions. Twenty-three health professionals participated in the
      consensus process. Results were analysed using quantitative and qualitative
      methods. Participants generated 12 solutions. One solution, developing mechanisms
      to increase family physicians' awareness of resources, was highly ranked for
      importance and feasibility by most participants. Another solution, providing
      family physicians with direct mental health support, was highly ranked as
      important but not as feasible by most participants. Deliberations emphasized the
      importance of case specific, as needed support based on the principles of shared
      care. The results suggest that practitioners highly value collaborative care but
      question the feasibility of implementing these principles in current Canadian
      primary care contexts.

PMID- 21738869
TI  - The Pharmacopsychometric Triangle to Illustrate the Effectiveness of T-PEMF
      Concomitant with Antidepressants in Treatment Resistant Patients: A Double-Blind,
      Randomised, Sham-Controlled Trial Revisited with Focus on the Patient-Reported
      Outcomes.
AB  - Background. Our T-PEMF trial has been revisited with focus on the
      pharmacopsychometric triangle in which effect size is used when comparing wanted
      versus unwanted clinical effects and quality of life as outcomes. In this
      analysis, we have especially focused on the self-reported HAM-D(6). Methods. The
      antidepressive medication which the patients were resistant to was kept unchanged
      during the five weeks of active versus sham T-PEMF. Results. In total 21,
      patients received active T-PEMF, and 19 patients received sham T-PEMF. The effect
      size was 1.02 and 0.90, respectively, on HAM-D(6) and HAM-D(6)-S. Concerning side
      effects, the active T-PEMF reduced the baseline score on concentration problems
      with an effect size of 0.44 while inducing more autonomic symptoms than sham T
      PEMF with an effect size of -0.41. The advantage of active over sham T-PEMF
      obtained an effect size of 0.48. Conclusion. Active T-PEMF was found superior to
      sham T-PEMF within the pharmacopsychometric triangle with a clinically
      significant effect size level above 0.40.

PMID- 21738870
TI  - Fasting Blood Glucose and Depressive Mood among Patients with Mental Illness in a
      Medicaid Managed Care Program.
AB  - Objective. This study explores the relationship between depressive symptoms, as
      measured by the PHQ-9 depression screen and blood glucose levels among patients
      with diabetes enrolled in Gold Choice, a Medicaid managed care program for
      individuals with mental illness and/or substance abuse. Methods. The PHQ-9 was
      mailed to 454 Gold Choice members and a questionnaire was mailed to their
      physicians requesting current HbA1c% and fasting blood glucose (FBG) levels. The
      pearson product-moment correlation was used to describe the association between
      PHQ-9 scores and FBG levels. Results. The PHQ-9 response rate was 55% (N = 249).
      Laboratory results were received for 141 patients. The correlation between FBG
      and PHQ-9 scores was modest but statistically significant: r = 0.21 , P = 0.015.
      Conclusion. A statistically significant association was found between FBG and PHQ
      9 depression scores. This finding supports current recommendations that
      physicians be alert to depressive symptoms among patients with diabetes or
      impaired glucose metabolism.

PMID- 21738871
TI  - Antidepressant therapy in severe depression may have different effects on ego
      dystonic and ego-syntonic suicidal ideation.
AB  - The objective of the present study was to investigate whether ego-dystonic and
      ego-syntonic suicidal ideation occurred at different frequencies during
      antidepressant therapy. A blind evaluation has been performed on records of 100
      suicides with a primary severe depression and 100 matched controls, admitted to
      the Department of Psychiatry, Lund, Sweden. Ego-dystonic suicidal ideation was
      more commonly reported during adequate treatment as compared to ego-syntonic
      ideation (P = .004). Men who committed suicide during adequate antidepressant
      therapy more often reported ego-dystonic suicidal ideation earlier in their lives
      compared with those who were not treated (P = .0377). This may indicate that
      treatment failure for ego-dystonic ideation was a precursor of their suicides.
      Consequently, ego-dystonic ideation seems to show a poorer response to
      antidepressant therapy as compared to ego-syntonic ideation, which may be more
      directly related to depression. Ego-dystonic ideation is proposed to be related
      to depressive psychosis.

PMID- 21738872
TI  - Depression care management: can employers purchase improved outcomes?
AB  - Fourteen vendors are currently selling depression care management products to US
      employers after randomized trials demonstrate improved work outcomes. The
      research team interviewed 10 (71.4%) of these vendors to compare their products
      to four key components of interventions demonstrated to improve work outcomes.
      Five of 10 depression products incorporate all four key components, three of
      which are sold by health maintenance organizations (HMOs); however, HMOs did not
      deliver these components at the recommended intensity and/or duration. Only one
      product delivered by a disease management company delivered all four components
      of care at the recommended intensity and duration. This "voltage drop," which we
      anticipate will increase with product implementation, suggests that every
      delivery system should carefully evaluate the design of its depression product
      before implementation for its capacity to deliver evidence-based care, repeating
      these evaluations as new evidence emerges.

PMID- 21738873
TI  - Automated analysis of crackles in patients with interstitial pulmonary fibrosis.
AB  - Background. The crackles in patients with interstitial pulmonary fibrosis (IPF)
      can be difficult to distinguish from those heard in patients with congestive
      heart failure (CHF) and pneumonia (PN). Misinterpretation of these crackles can
      lead to inappropriate therapy. The purpose of this study was to determine whether
      the crackles in patients with IPF differ from those in patients with CHF and PN.
      Methods. We studied 39 patients with IPF, 95 with CHF and 123 with PN using a 16
      channel lung sound analyzer. Crackle features were analyzed using machine
      learning methods including neural networks and support vector machines. Results.
      The IPF crackles had distinctive features that allowed them to be separated from
      those in patients with PN with a sensitivity of 0.82, a specificity of 0.88 and
      an accuracy of 0.86. They were separated from those of CHF patients with a
      sensitivity of 0.77, a specificity of 0.85 and an accuracy of 0.82. Conclusion.
      Distinctive features are present in the crackles of IPF that help separate them
      from the crackles of CHF and PN. Computer analysis of crackles at the bedside has
      the potential of aiding clinicians in diagnosing IPF more easily and thus helping
      to avoid medication errors.

PMID- 21738874
TI  - Bronchoscopic lung volume reduction.
AB  - The application of lung volume reduction surgery in clinical practice is limited
      by high postoperative morbidity and stringent selection criteria. This has been
      the impetus for the development of bronchoscopic approaches to lung volume
      reduction. A range of different techniques such as endobronchial blockers, airway
      bypass, endobronchial valves, thermal vapor ablation, biological sealants, and
      airway implants have been employed on both homogeneous as well as heterogeneous
      emphysema. The currently available data on efficacy of bronchoscopic lung volume
      reduction are not conclusive and subjective benefit in dyspnoea scores is a more
      frequent finding than improvements on spirometry or exercise tolerance. Safety
      data are more promising with rare procedure-related mortality, few serious
      complications, and short hospital length of stay. The field of bronchoscopic lung
      volume reduction continues to evolve as ongoing prospective randomized trials
      build on earlier feasibility data to clarify the true efficacy of such
      techniques.

PMID- 21738875
TI  - Gastroesophageal reflux and idiopathic pulmonary fibrosis: a review.
AB  - The histological counterpart of idiopathic pulmonary fibrosis is usual
      interstitial pneumonia, in which areas of fibrosis of various ages are
      interspersed with normal lung. This pattern could be explained by repeated
      episodes of lung injury followed by abnormal wound healing responses. The cause
      of the initiating alveolar epithelial injury is unknown, but postulated
      mechanisms include immunological, microbial, or chemical injury, including
      aspirated gastric refluxate. Reflux is promoted by low basal pressure in the
      lower oesophageal sphincter and frequent relaxations, potentiated by hiatus
      hernia or oesophageal dysmotility. In susceptible individuals, repeated
      microaspiration of gastric refluxate may contribute to the pathogenesis of IPF.
      Microaspiration of nonacid or gaseous refluxate is poorly detected by current
      tests for gastroesophageal reflux which were developed for investigating
      oesophageal symptoms. Further studies using pharyngeal pH probes, high-resolution
      impedance manometry, and measurement of pepsin in the lung should clarify the
      impact of reflux and microaspiration in the pathogenesis of IPF.

PMID- 21738876
TI  - Imaging the Gastrointestinal Tract of Small Animals.
AB  - Animal models of human diseases are increasingly available and are invaluable for
      studies of organ pathophysiology. Megacolon, abnormal dilatation of the colon not
      caused by mechanical obstruction, involves the destruction of the autonomic
      nervous system innervating the colon. Animal models of megacolon include mouse
      models of Chagas disease and Hirschprung's disease. Small animal imaging has
      become an important research tool and recent advances in preclinical imaging
      modalities have enhanced the information content available from longitudinal
      studies of animal models of human diseases. While numerous applications of
      imaging technologies have been reported to study the brain and heart of mouse
      models, fewer studies of the gastrointestinal system have been undertaken due to
      technical limitations caused by peristaltic and respiratory motion. Various
      imaging modalities relevant to study of the gastrointestinal tract of intact live
      animals are reviewed herein.

PMID- 21738878
TI  - Congratulations are due to Allergy, Asthma, & Immunology Research (AAIR) on being
      listed in Web of Science (SCIE).

PMID- 21738877
TI  - Analysis of Participant Reactivity in Dyads Performing a Videotaped Conflict
      Management Task.
AB  - Videotaping is used frequently in nursing research. A threat to the validity of
      videotaping is participant reactivity, that is, being recorded by a camera may
      influence the behavior of interest. This paper's purpose is to report how youth
      ages 10 to 14 years old and their parent viewed participation in a videotaped
      conflict-management task. Five dyads, who were part of a randomized clinical
      trial testing an intervention to promote parent-child communication, participated
      in a structured interview. All parents were mothers. Youth were eighth graders.
      Three were boys and two were girls. Findings indicated that (a) dyads felt that
      the videotaped interaction had a progression of feeling unnatural in the
      beginning to feeling natural toward the end, (b) dyads found it relatively easy
      to choose a topic of discussion, and (c) dyads felt that the discussions were
      meaningful. Based on these data, recommendations for researchers to reduce
      participant reactivity are provided.

PMID- 21738879
TI  - Role of TSLP in Nasal Polyp Inflammation.

PMID- 21738880
TI  - Management of rhinitis: allergic and non-allergic.
AB  - RHINITIS IS A GLOBAL PROBLEM AND IS DEFINED AS THE PRESENCE OF AT LEAST ONE OF
      THE FOLLOWING: congestion, rhinorrhea, sneezing, nasal itching, and nasal
      obstruction. The two major classifications are allergic and nonallergic rhinitis
      (NAR). Allergic rhinitis occurs when an allergen is the trigger for the nasal
      symptoms. NAR is when obstruction and rhinorrhea occurs in relation to
      nonallergic, noninfectious triggers such as change in the weather, exposure to
      caustic odors or cigarette smoke, barometric pressure differences, etc. There is
      a lack of concomitant allergic disease, determined by negative skin prick test
      for relevant allergens and/or negative allergen-specific antibody tests. Both are
      highly prevalent diseases that have a significant economic burden on society and
      negative impact on patient quality of life. Treatment of allergic rhinitis
      includes allergen avoidance, antihistamines (oral and intranasal), intranasal
      corticosteroids, intranasal cromones, leukotriene receptor antagonists, and
      immunotherapy. Occasional systemic corticosteroids and decongestants (oral and
      topical) are also used. NAR has 8 major subtypes which includes nonallergic
      rhinopathy (previously known as vasomotor rhinitis), nonallergic rhinitis with
      eosinophilia, atrophic rhinitis, senile rhinitis, gustatory rhinitis, drug
      induced rhinitis, hormonal-induced rhinitis, and cerebral spinal fluid leak. The
      mainstay of treatment for NAR are intranasal corticosteroids. Topical
      antihistamines have also been found to be efficacious. Topical anticholinergics
      such as ipratropium bromide (0.03%) nasal spray are effective in treating
      rhinorrhea symptoms. Adjunct therapy includes decongestants and nasal saline.
      Investigational therapies in the treatment of NAR discussed include capsaicin,
      silver nitrate, and acupuncture.

PMID- 21738881
TI  - Occupational asthma: etiologies and risk factors.
AB  - The purpose of this article is to critically review the available evidence
      pertaining to occupational, environmental, and individual factors that can affect
      the development of occupational asthma (OA). Increasing evidence suggests that
      exploration of the intrinsic characteristics of OA-causing agents and associated
      structure-activity relationships offers promising avenues for quantifying the
      sensitizing potential of agents that are introduced in the workplace. The
      intensity of exposure to sensitizing agents has been identified as the most
      important environmental risk factor for OA and should remain the cornerstone for
      primary prevention strategies. The role of other environmental co-factors (e.g.,
      non-respiratory routes of exposure and concomitant exposure to cigarette smoke
      and other pollutants) remains to be further delineated. There is convincing
      evidence that atopy is an important individual risk factor for OA induced by high
      molecular-weight agents. There is some evidence that genetic factors, such as
      leukocyte antigen class II alleles, are associated with an increased risk of OA;
      however, the role of genetic susceptibility factors is likely to be obscured by
      complex gene-environment interactions. OA, as well as asthma in general, is a
      complex disease that results from multiple interactions between environmental
      factors and host susceptibilities. Determining these interactions is a crucial
      step towards implementing optimal prevention policies.

PMID- 21738882
TI  - Regulatory B cells and allergic diseases.
AB  - B cells are generally considered to positively regulate immune responses by
      producing antigen-specific antibodies. B cells are classified into classical CD5(
      ) conventional B cells and CD5(+) B1 cells. The latter produce multi-specific
      autoantibodies and are thought to be involved in autoimmune diseases. However,
      evidence supporting a B cell negative regulatory function has accumulated over
      the past 30 years. Multiple reports have suggested that absence, or loss, of
      regulatory B cells exacerbates symptoms of both allergic (including contact
      hypersensitivity and anaphylaxis) and autoimmune (such as experimental autoimmune
      encephalomyelitis, chronic colitis, and collagen-induced arthritis) diseases, and
      in lupus-like models of autoimmunity. Regulatory B cells are characterized by
      production of the negative regulatory cytokines, IL-10 and TGF-beta. IL-10
      producing B cells were the first regulatory B cells to be recognized and were
      termed 'B10' cells. IL-10-producing regulatory B cells are of the
      CD19(+)CD5(+)IgM(hi)IgD(lo)CD1d(hi) type. Recently, a TGF-beta-producing
      regulatory B cell subset, Br3, has been shown to be related to immune tolerance
      in food allergies. Moreover, forkhead box P3 (Foxp3)-expressing B cells have also
      been identified in humans and may act as regulatory B cells (Bregs). The
      functional image of regulatory B cells is similar to that of regulatory T cells.
      Because of the proliferative and apoptotic responses of Br1 and Br3 cells in
      immune tolerance in non-IgE-mediated food allergy, reciprocal roles and counter
      regulatory mechanisms of Br1 and Br3 responses are also suspected. Additionally,
      different roles for regulatory B and T cells at different time points during
      initiation and progression of autoimmune disease are described.

PMID- 21738883
TI  - Personal Factors Affecting Therapeutic Responses to BCG Vaccination in
      Asthmatics.
AB  - PURPOSE: Bacille Calmette-Guerin (BCG) vaccination has been reported to be an
      effective treatment for asthma in several animal models. This study investigated
      whether the response to BCG treatment in asthma depends on subject clinical
      characteristics. METHODS: Stable asthma patients were vaccinated with BCG. One
      month later, alterations in pulmonary function after vaccination and their
      relationships with subject clinical characteristics were determined. RESULTS: Of
      149 patients with asthma, 54 (36.2%) showed a good or fair response to BCG. The
      DeltaFEV1 after vaccination was significantly related to age (r=-0.348, P<0.001),
      peripheral blood eosinophil counts (r=0.315, P<0.001) and baseline FEV1,
      expressed as % personal best value (r=-0.474, P<0.001), but not to FEV1 %
      predicted value (r=-0.066, P>0.05). A good/fair response was highly prevalent in
      atopic females compared with atopic males, especially among those aged <=50 years
      (90.9% vs. 40.0%, P=0.024). Age (P<0.001, odds ratios (OR)=0.92, confidence
      interval (CI)=0.88-0.96) and atopy (P<0.01, OR=4.95, CI=1.70-14.44) were
      significant predictors for a good/fair response in females. However, blood
      eosinophil counts (P<0.05, OR=1.18, CI=1.01-1.39) and FEV1 % best (P<0.001,
      OR=0.86, CI=0.79-0.94), but not age or atopy, were significant predictors in
      males. Approximately three-quarters of the males were smokers. CONCLUSIONS: The
      therapeutic effect of BCG in asthma may differ according to patient clinical
      characteristics. The greatest benefit occurred in young atopic females. Asthma
      activity indices, such as eosinophilia and FEV1 % best, were more predictive of a
      good/fair response in males; this may have been related to cigarette smoking.

PMID- 21738884
TI  - Increased expression and role of thymic stromal lymphopoietin in nasal polyposis.
AB  - PURPOSE: Nasal polyposis is a chronic inflammatory disease of the upper airways
      often associated with asthma and characterized by markedly increased numbers of
      eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells.
      Previous studies have shown elevated levels of thymic stromal lymphopoietin
      (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal
      models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in
      nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and
      its potential role in nasal polyposis. METHODS: Messenger RNA expression for
      TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived
      chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was
      analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the
      nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by
      immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining
      and nasal polyp tissue IgE, by ELISA. RESULTS: Messenger RNA expression for
      TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic
      nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells,
      endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and
      nasal polyps. The number of TSLP+ cells was significantly greater in the nasal
      mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from
      atopics was significantly greater than that of non-atopics and that in the
      allergic nasal mucosa. The number of TSLP+ cells correlated well with the number
      of eosinophils and the levels of IgE in nasal polyps. CONCLUSIONS: The high
      expression of TSLP in nasal polyps and its strong correlation to eosinophils and
      IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by
      regulating the Th2 type and eosinophilic inflammation.

PMID- 21738885
TI  - Vancomycin-associated spontaneous cutaneous adverse drug reactions.
AB  - PURPOSE: With the increase in vancomycin use, adverse drug reactions (ADRs)
      associated with vancomycin have been reported increasingly more often. However,
      the characteristics of cutaneous ADRs with and without systemic reactions (SRs)
      have not been described. This study investigated the characteristics of
      spontaneously reported and assessed ADRs associated with vancomycin by a
      pharmacovigilance center. METHODS: ADRs (n=121) associated with vancomycin in 96
      patients were collected from 2008 to 2009. Records from physician- and nurse
      reported suspected cases of vancomycin ADRs, ADR type, latent period, and
      laboratory results were compared between cutaneous ADRs with and without SRs.
      RESULTS: The main vancomycin-related ADRs were skin rashes (47.9%), hematologic
      abnormalities (17.36%), fever (12.4%), and elevated serum creatinine (12.4%).
      Significant differences were observed in latent period (days) and the mean change
      in eosinophils (%) between cutaneous (9.21+/-9.71 and 1.4+/-3.4, respectively)
      and other ADRs (14.03+/-11.71 and -0.5+/-3.5, respectively). Twelve cases of
      cutaneous ADRs with SRs had been initially reported as cutaneous ADRs only. Mean
      changes in the eosinophil count were significantly higher for cutaneous ADRs with
      SRs compared to those without SRs. CONCLUSIONS: Skin rashes accompanied by
      peripheral eosinophilia, representing suspected immune-mediated delayed
      hypersensitivity reactions, are a common vancomycin ADR. For the early and exact
      detection of ADRs associated with vancomycin administration, close monitoring of
      laboratory tests, including complete blood counts with differential analysis, is
      recommended.

PMID- 21738886
TI  - The Role of Plasmacytoid and Myeloid Dendritic Cells in Induction of Asthma in a
      Mouse Model and the Effect of a TLR9 Agonist on Dendritic Cells.
AB  - PURPOSE: To determine the role of plasmacytoid dendritic cells (pDC) and myeloid
      dendritic cells (mDC) in priming effector T cells to induce allergy, and to
      evaluate the effect of immunostimulatory sequences (ISS, TLR9 agonist) on
      dendritic cells. METHODS: Cultured mDC and pDC with/without ISS were injected
      intratracheally into sensitized Balb/C mice. Mice were sacrificed, and then
      pulmonary function tests, bronchoalveolar lavage (BAL), cell counts, and cytokine
      levels were evaluated. Migration of dendritic cells was also evaluated after ISS
      administration. RESULTS: In mice injected with mDC, airway hyperresponsiveness,
      eosinophil counts, and Th2 cytokine levels in BAL increased with increasing
      numbers of mDC injected. However, in mice injected with pDC, none of these
      changed, suggesting poor priming of T cells by pDC. In addition, mDC pulsed with
      ISS inhibited asthmatic reactions, and ISS administration inhibited migration of
      DC to the lung. CONCLUSIONS: We suggest that pDC played a limited role in priming
      T cells in this asthma model and that mDC played a major role in inducing asthma.
      In addition, ISS inhibited migration of DC to the lung.

PMID- 21738887
TI  - Mesenchymal stem cell transfer suppresses airway remodeling in a toluene
      diisocyanate-induced murine asthma model.
AB  - PURPOSE: Severe asthma is characterized by high medication requirements to
      maintain good disease control or by persistent symptoms despite high medication
      use. The transfer of bone marrow-derived mesenchymal stem cells (BMDMSCs) to the
      injured lungs is a possible treatment for severe asthma. This study investigated
      the therapeutic effects of BMDMSCs in airway remodeling and inflammation in an
      experimental toluene diisocyanate (TDI)-induced asthma animal model of severe
      asthma. METHODS: BMDMSCs were transferred into rats after TDI inhalation.
      Bronchoalveolar lavage (BAL) cell profiles, histological changes including an
      inflammatory index and goblet cell hyperplasia, and the airway response to
      methacholine using plethysmography were analyzed. Smooth muscle actin (SMA) and
      proliferating cell nuclear antigen (PCNA) protein expression were observed in
      lung tissue using immunohistochemical staining. The collagen content was measured
      in lung tissue sections and lung extracts using Masson's trichrome staining and
      an immunoassay kit. RESULTS: The numbers of inflammatory cells in BAL fluid,
      histological inflammatory index, airway response to methacholine, number of
      goblet cells, and amount of collagen were increased in TDI-treated rats compared
      with sham rats (P=0.05-0.002). BMDMSC transfer significantly reduced the TDI
      induced increase in the inflammatory index and numbers of eosinophils and
      neutrophils in BAL fluid to levels seen in sham-treated rats (P<0.05). BMDMSC
      transfer significantly reduced the number of goblet cells, collagen deposition,
      and immune staining for SMA and PCNA with concomitant normalization of the airway
      response to methacholine. CONCLUSIONS: The systemic transfer of BMDMSCs
      effectively reduced experimental TDI-induced airway inflammation and remodeling
      and airway hyperreactivity.

PMID- 21738888
TI  - Occupational Asthma Induced by the Reactive Dye Synozol Red-K 3BS.
AB  - Various reactive dyes can elicit occupational asthma in exposed textile industry
      workers. To date, there has been no report of occupational asthma caused by the
      red dye Synozol Red-K 3BS (Red-K). Here, we report a 38-year-old male textile
      worker with occupational asthma and rhinitis induced by inhalation of Red-K. He
      showed positive responses to Red-K extract on skin-prick testing and serum
      specific IgE antibodies to Red-K-human serum albumin conjugate were detected
      using an enzyme-linked immunosorbent assay. A bronchoprovocation test with Red-K
      extract resulted in significant bronchoconstriction. These findings suggest that
      the inhalation of the reactive dye Red-K can induce IgE-mediated occupational
      asthma and rhinitis in exposed workers.

PMID- 21738889
TI  - Assessment of mandibular advancement surgery with 3D CBCT models superimposition.
AB  - OBJECTIVES: To assess surgery and short-term post-surgery changes in the position
      of the condyles, rami and chin after mandibular advancement.  METHODOLOGY: Pre
      surgery (T1), 1 week post-surgery (T2), and 6 week post-surgery (T3) CBCT scans
      were acquired for 20 retrognathic patients with short or normal face height. 3D
      models were built and superimposed through a fully automated voxel-wise method
      using the cranial base of the pre-surgery scan as reference. Anatomic regions of
      interest were selected and analyzed separately. Within-subject surface distances
      between T1-T2, T2-T3, and T1-T3 were computed. Color-coded maps and semi
      transparent display of overlaid structures allowed the evaluation of displacement
      directions.  RESULTS: After an antero-inferior chin displacement with surgery in
      all cases (>4 mm in 87.5%), 25% of the patients showed some kind of posterior
      movement (< 3 mm), and 69% showed an antero-superior movement after splint
      removal. Comparing T1-T3, an antero-inferior (87.5% of the cases) or only
      inferior (12.5%) displacement was observed (>4 mm in 80%). Considering all
      directions of displacement, the surface distance differences for the condyles and
      rami were small: 77.5% of the condyles moved <2 mm with surgery (T1-T2), and 90%
      moved <2 mm in the short-term (T2-T3) and in the total evaluation (T1-T3), while
      the rami showed a <3 mm change with surgery in 72.5% of the cases, and a <2 mm
      change in 87.5% (T2-T3) and in 82% (T1-T3).  CONCLUSIONS: Expected displacements
      with surgery were observed and post-surgery changes suggested a short-term
      adaptive response toward recovery of condyle and ramus displacements. The changes
      on the chin following splint removal suggested an acceptable adaptation, but with
      considerable individual variability.

PMID- 21738890
TI  - The importance of global studies of the genetics of type 2 diabetes.
AB  - Genome wide association analyses have revealed large numbers of common variants
      influencing predisposition to type 2 diabetes and related phenotypes. These
      studies have predominantly featured European populations, but are now being
      extended to samples from a wider range of ethnic groups. The transethnic analysis
      of association data is already providing insights into the genetic, molecular and
      biological causes of diabetes, and the relevance of such studies will increase as
      human discovery genetics increasingly moves towards sequencing-based approaches
      and a focus on low frequency and rare variants.

PMID- 21738891
TI  - The causes and consequences of low levels of high density lipoproteins in
      patients with diabetes.
AB  - Type 2 diabetes is commonly accompanied by a low level of high density
      lipoprotein cholesterol (HDL-C) that contributes to the increased cardiovascular
      risk associated with this condition. Given that HDLs have the ability to improve
      increase the uptake of glucose by skeletal muscle and to stimulate the secretion
      of insulin from pancreatic beta cells the possibility arises that a low HDL
      concentration in type 2 diabetes may also contribute to a worsening of diabetic
      control. Thus, there is a double case for raising the level of HDL-C in patients
      with type 2 diabetes: to reduce cardiovascular risk and to improve glycemic
      control. Approaches to raising HDL-C include lifestyle factors such as weight
      reduction, increased physical activity and stopping smoking. Of currently
      available drugs, the most effective is niacin. Newer formulations of niacin are
      reasonably well tolerated and have the ability to increase HDL-C by up to 30%.
      The effect of niacin on cardiovascular events in type 2 diabetes is currently
      being tested in a large-scale clinical outcome trial.

PMID- 21738892
TI  - The prediabetic period: review of clinical aspects.
AB  - Hyperglycemia that does not satisfy the diagnostic criteria for diabetes mellitus
      (DM) is generally called prediabetes (preDM). The global prevalence of preDM has
      been increasing progressively in the past few decades, and it has been
      established that preDM status is a strong risk factor for DM and cardiovascular
      disease. Currently, preDM status is classified into two subtypes: impaired
      fasting glucose and impaired glucose tolerance. Currently, preDM is not regarded
      as an independent clinical entity, but only as a risk factor for others. In this
      article, we review various clinical aspects of preDM in terms of the working
      definition, changes in criteria over the years, epidemiology, and
      pathophysiological characteristics, and its clinical significance in current
      medicine.

PMID- 21738893
TI  - Candidate dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes.

PMID- 21738894
TI  - Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the
      Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig
      Pancreatic Cells into Beta-Cells.
AB  - BACKGROUND: A limitation in the number of insulin-producing pancreatic beta-cells
      is a special feature of diabetes. The identification of alternative sources for
      the induction of insulin-producing surrogate beta-cells is a matter of profound
      importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpression have been shown to
      influence the differentiation and proliferation of pancreatic stem cells.
      However, few studies have been conducted using adult animal pancreatic stem
      cells. METHODS: Adult pig pancreatic cells were prepared from the non-endocrine
      fraction of adult pig pancreata. Porcine neonatal pancreas cell clusters (NPCCs)
      were prepared from neonatal pigs aged 1-2 days. The dispersed pancreatic cells
      were infected with PDX-1/VP16, BETA2/NeuroD, and MafA adenoviruses. After
      infection, these cells were transplanted under the kidney capsules of
      normoglycemic nude mice. RESULTS: The adenovirus-mediated overexpression of PDX
      1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in
      adult pig pancreatic cells. Immunocytochemistry revealed that the number of
      insulin-positive cells in NPCCs and adult pig pancreatic cells was approximately
      2.6- and 1.1-fold greater than those in the green fluorescent protein control
      group, respectively. At four weeks after transplantation, the relative volume of
      insulin-positive cells in the grafts increased in the NPCCs, but not in the adult
      porcine pancreatic cells. CONCLUSION: These data indicate that PDX-1,
      BETA2/NeuroD, and MafA facilitate the beta-cell differentiation of NPCCs, but not
      adult pig pancreatic cells. Therefore PDX-1, BETA2/NeuroD, and MafA-induced NPCCs
      can be considered good sources for the induction of pancreatic beta-cells, and
      may also have some utility in the treatment of diabetes.

PMID- 21738895
TI  - Effects of spironolactone and losartan on diabetic nephropathy in a type 2
      diabetic rat model.
AB  - BACKGROUND: While there is an evidence that the anti-inflammatory properties of
      spironolactone can attenuate proteinuria in type 2 diabetes, its effects on
      vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have
      not been clearly defined. In this study, we examined the effects of
      spironolactone, losartan, and a combination of these two drugs on albuminuria,
      renal VEGF expression, and inflammatory and oxidative stress markers in a type 2
      diabetic rat model. METHODS: Thirty-three Otsuka-Long-Evans-Tokushima-Fatty
      (OLETF) rats were divided into four groups and treated with different medication
      regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone
      treated (n=10), losartan-treated (n=9), and combination of spironolactone- and
      losartan-treated (n=9). RESULTS: At week 50, the albumin-to-creatinine ratio was
      significantly decreased in the losartan and combination groups compared to the
      control OLETF group. No decrease was detected in the spironolactone group. There
      was a significant reduction in renal VEGF, transforming growth factor (TGF)-beta,
      and type IV collagen mRNA levels in the spironolactone- and combination regimen
      treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were
      comparable in all four groups but did show a decreasing trend in the losartan and
      combination regimen groups. Twenty-four hour urine malondialdehyde levels were
      significantly decreased in the spironolactone- and combination regimen-treated
      groups. CONCLUSION: These results suggest that losartan alone and a combined
      regimen of spironolactone and losartan could ameliorate albuninuria by reducing
      renal VEGF expression. Also, simultaneous treatment with spironolactone and
      losartan may have protective effects against diabetic nephropathy by decreasing
      TGF-beta and type IV collagen expression and by reducing oxidative stress in a
      type 2 diabetic rat model.

PMID- 21738896
TI  - The association of unintentional changes in weight, body composition, and
      homeostasis model assessment index with glycemic progression in non-diabetic
      healthy subjects.
AB  - BACKGROUND: We performed a retrospective longitudinal study on the effects of
      changes in weight, body composition, and homeostasis model assessment (HOMA)
      indices on glycemic progression in subjects without diabetes during a four-year
      follow-up period in a community cohort without intentional intervention. METHODS:
      From 28,440 non-diabetic subjects who participated in a medical check-up program
      in 2004, data on anthropometric and metabolic parameters were obtained after four
      years in 2008. Body composition analyses were performed with a bioelectrical
      impedance analyzer. Skeletal muscle index (SMI, %) was calculated with lean
      mass/weight*100. Subjects were divided into three groups according to weight
      change status in four years: weight loss (<=-5.0%), stable weight (-5.0 to 5.0%),
      weight gain (>=5.0%). Progressors were defined as the subjects who progressed to
      impaired fasting glucose or diabetes. RESULTS: Progressors showed worse baseline
      metabolic profiles compared with non-progressors. In logistic regression
      analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR) in four
      years presented higher odds ratios for glycemic progression compared with other
      changes during that period. Among the components of body composition, a change in
      waist-hip ratio was the strongest predictor, and SMI change in four years was a
      significant negative predictor for glycemic progression. Changes in HOMA beta
      cell function in four years was a negative predictor for glycemic progression.
      CONCLUSION: Increased interval changes in HOMA-IR, weight gain and waist-hip
      ratio was associated with glycemic progression during a four-year period without
      intentional intervention in non-diabetic Korean subjects.

PMID- 21738897
TI  - Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus
      and Effect of DPP-4 Inhibitor Treatment on ADA Activity.
AB  - BACKGROUND: Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with
      adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated
      whether ADA activity is specifically affected by treatment with DPP-4 inhibitor
      (DPP4I) compared with other anti-diabetic agents. METHODS: Fasting ADA activity,
      in addition to various metabolic and biochemical parameters, were measured in 262
      type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and
      in 46 non-diabetic control subjects. RESULTS: ADA activity was increased in T2DM
      patients compared with that in non-diabetic control subjects (mean+/-standard
      error, 23.1+/-0.6 U/L vs. 18.6+/-0.8 U/L; P<0.05). ADA activity was correlated
      with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate
      aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248,
      P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly
      controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1+/
      0.8 U/L vs. 25.4+/-1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM
      patients did not differ from those of other oral anti-diabetic agents or insulin.
      T2DM patients on metformin monotherapy showed a lower ADA activity (20.9+/-1.0
      U/L vs. 28.1+/-2.8 U/L; P<0.05) compared with that of those on sulfonylurea
      monotherapy. CONCLUSION: Our results show that ADA activity is increased in T2DM
      patients compared to that in non-diabetic patients, is positively correlated with
      blood glucose level, and that DPP4I has no additional specific effect on ADA
      activity, except for a glycemic control- or HbA1c-dependent effect.

PMID- 21738898
TI  - Predictive clinical parameters for the therapeutic efficacy of sitagliptin in
      korean type 2 diabetes mellitus.
AB  - BACKGROUND: Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4)
      inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and
      glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased
      insulin secretion. While studies conducted in other countries have indicated the
      efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus
      (T2DM), its predictors of effects to sitagliptin are not well understood.
      Therefore, we evaluated the predictive clinical parameters for the therapeutic
      benefits of sitagliptin when added to an ongoing metformin or sulfonylurea
      therapy in Korean T2DM subjects. METHODS: We obtained data from 251 Korean T2DM
      subjects who had recently started taking sitagliptin as add-on therapy. Exclusion
      criteria included any insulin use. Changes in HbA1c (DeltaHbA1c) and fasting
      plasma glucose (DeltaFPG) were assessed by comparing baseline levels prior to
      sitagliptin administration to levels 12 and 24 weeks after treatment. Responders
      were defined as subjects who experienced decrease from baseline of >10% in
      DeltaHbA1c or >20% in DeltaFPG levels at 24 weeks. RESULTS: We classified 81% of
      the subjects (204 out of 251) as responders. The responder group had a lower mean
      body mass index (23.70+/-2.40 vs. 26.00+/-2.26, P<=0.01) and were younger
      (58.83+/-11.57 years vs. 62.87+/-12.09 years, P=0.03) than the non-responder
      group. CONCLUSION: In Korean T2DM subjects, sitagliptin responders had lower body
      mass index and were younger compared to non-responders.

PMID- 21738899
TI  - Increasing trend in the number of severe hypoglycemia patients in Korea.
AB  - BACKGROUND: To investigate whether the number of subjects with severe
      hypoglycemia who are brought to a hospital emergency department is increasing and
      to identify whether there have been changes in the demographic and clinical
      characteristics of those subjects. METHODS: We analyzed data from the Emergency
      Departments of two general hospitals in Seoul, Korea. We included data from all
      adult subjects with type 2 diabetes who presented to an emergency department with
      severe hypoglycemia between January 1, 2004 and December 30, 2009. RESULTS: A
      total of 740 cases of severe hypoglycemia were identified. The mean subject age
      was 69+/-12 years, mean duration of diabetes was 13.8+/-9.3 years, and 53.2% of
      subjects were receiving insulin therapy. We observed a sharp rise in the number
      of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed
      in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%.
      The mean subject age, duration of diabetes, HbA1c level, and renal and insulin
      secretory function values did not change significantly during the study period.
      The proportion of glimepiride use increased, while use of gliclazide decreased
      among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI
      decreased among insulin users. CONCLUSION: We identified a sharp increase in the
      number of subjects with severe hypoglycemia presenting to an emergency room since
      2006. The clinical characteristics of these subjects did not change markedly
      during the study period. Nationwide studies are warranted to further clarify this
      epidemic of severe hypoglycemia.

PMID- 21738900
TI  - A survey of diabetic educators and patients for the revision of korean food
      exchange lists.
AB  - BACKGROUND: Food exchange lists are one of the main methods of nutritional
      education. However, Korean food exchange lists have not been revised since 1994.
      Therefore, we surveyed the opinions of diabetes educators and patients with
      diabetes regarding the need for revision of the current food exchange lists.
      METHODS: For two weeks beginning on 10 March 2008, a 12-item questionnaire
      regarding the opinion and need for revision of the current food exchange lists
      was e-mailed to diabetes educators nationwide. Another 15-question survey was
      administered to patients with diabetes in 13 hospitals located in the Seoul and
      Gyeonggi regions of Korea. RESULTS: We obtained survey responses from 101
      diabetes educators and 209 patients; 65 (64.3%) of the educators answered that
      the current food exchange lists should be revised. The items that needed revision
      were the glycemic index, addition of new foods and reaffirmation of exchange
      standard amounts. The patients demanded specific education about choosing
      appropriate foods, a balanced meal plan, proper snacks, and dining intake.
      CONCLUSION: Our survey results demonstrate the need to revise the Korean food
      exchange lists. This process should focus on glycemic index, the addition of new
      foods and reconfirmation of one exchange reference unit.

PMID- 21738901
TI  - Evaluation of stress in korean patients with diabetes mellitus using the problem
      areas in diabetes-Korea questionnaire.
AB  - BACKGROUND: It is known that diabetes and stress are directly or indirectly
      related, and that it is important to evaluate stress in patients with diabetes.
      The relationship between Korean diabetics and diabetes-related stress has never
      been reported. The objective of this study was to develop a stress questionnaire
      suitable for use with Korean diabetics and to evaluate its utility. METHODS: This
      study subjects were 307 Korean diabetics, aged 40 to 74 years old, who visited
      the Department of Endocrinology and Metabolism at Gachon University Gil Hospital,
      Yeungnam University Medical Center, and Inha University Hospital in Korea between
      March 2006 and February 2008. We developed a Korean version of Polonsky's Problem
      Areas in Diabetes (PAID) stress questionnaire (PAID-K) and used it to assess
      degrees of stress in our sample of Korean patients. We evaluated the utility of
      the questionnaire and analyzed the relationships between clinical characteristics
      of the study subjects and degrees of stress. RESULTS: Cronbach's alpha for PAID-K
      was 0.95, and PAID-K scores were significantly correlated with Hypoglycemia Fear
      Survey scores (r=0.44, P<0.05) and State Trait Anxiety Inventory-6 scores
      (r=0.21, P<0.05). PAID-K scores were significantly higher in patients with longer
      durations of diabetes, patients using insulin, and female patients (P=0.02,
      P=0.038, and P=0.001, respectively). The score also tended to increase as HbA1c
      levels increased, except for very high HbA1c levels (above 11%) (P for
      trend<0.05). CONCLUSION: We developed the PAID-K questionnaire and demonstrated
      its utility to evaluate levels of stress in diabetic patients in Korea.

PMID- 21738902
TI  - Letter: Basal C-peptide Level as a Surrogate Marker of Subclinical
      Atherosclerosis in Type 2 Diabetes Patients (Diabetes Metab J 2011;35:41-9).

PMID- 21738903
TI  - Response: Basal C-peptide Level as a Surrogate Marker of Subclinical
      Atherosclerosis in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:41-9).

PMID- 21738904
TI  - VARIATIONAL LEVEL-SET WITH GAUSSIAN SHAPE MODEL FOR CELL SEGMENTATION.
AB  - In analysis of microscopy based images, a major challenge lies in splitting apart
      cells that appear to overlap because they are too densely packed. This task is
      complicated by the physics of the image acquisition that causes large variations
      in pixel intensities. Each image typically contains thousands of cells with each
      cell having a different orientation, size and intensity histogram. In this paper,
      a spatial intensity model of a nucleus is incorporated into [1] to aid cell
      segmentation from microscopy datasets. An energy functional is defined and with
      it the spatial intensity distribution of a nuclei is modeled as a Gaussian
      distribution with constant intensity background. Experimental results on a
      variety of microscopic data validate its effectiveness.

PMID- 21738905
TI  - Antibiotic therapy and fat digestion and absorption in cystic fibrosis.
AB  - Antibiotic therapy in the cystic fibrosis (CF) mouse model has been shown to
      result in reduced bacterial load of the intestine and significant body mass gain.
      The effect was suggested to be linked to the improvement of intestinal digestion
      and absorption. Therefore, we aimed to assess the influence of routinely applied
      antibiotic therapy in CF patients on fat assimilation. Twenty-four CF patients
      aged 6 to 30 years entered the study. Inclusion criteria comprised confirmed
      exocrine pancreatic insufficiency and bronchopulmonary exacerbation demanding
      antibiotic therapy. Exclusion criteria comprised: antibiotic therapy six weeks
      prior to the test, liver cirrhosis, diabetes mellitus, oxygen dependency, the use
      of systemic corticosteroids. In all enrolled CF subjects, (13)C-labelled mixed
      triglyceride breath test ((13)C MTG-BT) was performed to assess lipid digestion
      and absorption, before and after antibiotic therapy. Sixteen subjects were
      treated intravenously with ceftazidime and amikacin, eight patients orally with
      ciprofloxacin. Cumulative percentage dose recovery (CPDR) was considered to
      reflect digestion and absorption of lipids. The values are expressed as means
      (medians). The values of CPDR before and after antibiotic therapy did not differ
      in the whole studied group [4.6(3.3) % vs. 5.7(5.3) %, p = 0.100] as well as in
      the subgroup receiving them intravenously [4.6(3.2) % vs. 5.7(5.3) %, p = 0.327]
      or in that with oral drug administration [4.6(3.4) % vs. 5.7(5.4) %, p = 0.167].
      In conclusion, antibiotic therapy applied routinely in the course of pulmonary
      exacerbation in CF patients does not seem to result in an improvement of fat
      digestion and absorption.

PMID- 21738906
TI  - A novel technique for preparing an allograft fibula for use as a transsacral
      graft as treatment for high-grade spondylolisthesis.
AB  - We describe a novel technique for preparing a fibular allograft for use as a
      transsacral strut with an anterior cruciate ligament (ACL) coring reamer for
      stabilization of high-grade spondylolisthesis deformities involving the L5--S1
      segment in conjunction with instrumented posterolateral fusions. Over 4 years, 6
      patients underwent instrumented posterolateral fusions from L3 or L4 to the
      sacrum or ileum plus posterior implantation of transsacral fibular allografts
      fashioned with an ACL coring reamer (Arthrex, Naples, Florida). No intraoperative
      complications were noted. At most recent follow-up (1-6 years), 5 of the patients
      reported no adverse events; the sixth patient reported prominent hardware, which
      was removed 5 years after the index surgery. ACL coring reamers seem to
      facilitate processing of fibular allografts so that they may be used as
      transsacral dowels for stabilizing high-grade L5--S1 spondylolisthesis
      deformities.

PMID- 21738907
TI  - Highly-photoluminescent ZnSe nanocrystals via a non-injection-based approach with
      precursor reactivity elevated by a secondary phosphine.
AB  - Highly-photoluminescent ZnSe quantum dots with 72% quantum yield and 22 nm full
      width at half maximum were synthesized with more reactive precursors via a non
      injection approach with high synthetic reproducibility; (31)P NMR provided
      insight into the formation mechanisms of ZnSe monomers.

PMID- 21738908
TI  - Direct amidation of azoles with formamides via metal-free C-H activation in the
      presence of tert-butyl perbenzoate.
AB  - A novel and simple method for the direct amidation of azoles with formamides has
      been developed. The reaction could occur smoothly in the presence of tert-butyl
      perbenzoate (TBPB) as an oxidant under metal- and base-free conditions. Direct
      dehydrogenative cross-coupling of formamides and azoles generated the
      corresponding products in good yields.

PMID- 21738909
TI  - Hg2+ recognition by triptycene-derived heteracalixarenes: selectivity tuned by
      bridging heteroatoms and macrocyclic cavity.
AB  - The binding properties of triptycene-derived oxacalixarenes containing 1,8
      naphthyridine subunits 1a and 1b toward metal ions were investigated in detail by
      spectroscopic methods. A couple of new N,O-bridged diazadioxacalixarenes 2a, 2b
      were synthesized and their binding properties to metal ions were also evaluated.
      The results showed that the oxacalixarene 1a, a cis-isomer with a boat-like 1,3
      alternate conformation and a symmetrical cavity structure, exhibited a highly
      selective fluorescence response toward Hg(2+) ions, while 1b, 2a and 2b did not
      show selective response towards any specific metal ions. Such selectivity can
      thus be controlled by the bridging heteroatoms and cavity structures of the
      macrocycles. Moreover, it was found that the fluorescence of 1a was considerably
      quenched upon the addition of Hg(2+), and a 1 : 2 stoichiometry host-guest
      complex was proposed on the basis of the Job plot and (1)H NMR titrations.

PMID- 21738910
TI  - Transparent and flexible electrodes and supercapacitors using polyaniline/single
      walled carbon nanotube composite thin films.
AB  - Large-scale transparent and flexible electronic devices have been pursued for
      potential applications such as those in touch sensors and display technologies.
      These applications require that the power source of these devices must also
      comply with transparent and flexible features. Here we present transparent and
      flexible supercapacitors assembled from polyaniline (PANI)/single-walled carbon
      nanotube (SWNT) composite thin film electrodes. The ultrathin, optically
      homogeneous and transparent, electrically conducting films of the PANI/SWNT
      composite show a large specific capacitance due to combined double-layer
      capacitance and pseudo-capacitance mechanisms. A supercapacitor assembled using
      electrodes with a SWNT density of 10.0 ug cm(-2) and 59 wt% PANI gives a specific
      capacitance of 55.0 F g(-1) at a current density of 2.6 A g(-1), showing its
      possibility for transparent and flexible energy storage.

PMID- 21738911
TI  - Artificial polymeric receptors on the cell surface promote the efficient cellular
      uptake of quantum dots.
AB  - In our previous paper, secondary-amine appended cationic polymer 1 was used as a
      scaffold to display artificial receptors on a cell surface (R. Kamitani et al.,
      ChemBioChem, 2009, 10, 230). This polymer can be retained on the cell surface for
      more than 30 min before being slowly internalized into the cells. In this study,
      our aim is to achieve the efficient internalization of quantum dots (QDs) into
      target cells via artificial receptors on the polymer. As a receptor molecule, N
      acetylglucosamine (GlcNAc) moieties were introduced into the polymer, and GlcNAc
      binding protein-displaying QDs were used as a ligand. We found that ligand
      presenting QDs could be internalized effectively into cells via polymer-mediated
      endocytosis, whereas QDs were not internalized into untreated cells. These data
      suggest that our method based on cell-surface engineering using polymers affords
      a new approach to the delivery of various poorly permeable nanoparticles into
      cells.

PMID- 21738912
TI  - Chemical and photochemical oxidation of organic substrates by ruthenium aqua
      complexes with water as an oxygen source.
AB  - Two ruthenium aqua complexes were shown to be effective catalysts in chemical and
      photochemical oxidation of hydrocarbons. A remarkable activity (up to 90% yield
      and 100% selectivity) was performed in conversion of sulfide to sulfoxide by
      homogeneous photooxidation.

PMID- 21738913
TI  - Single-molecule interfacial electron transfer dynamics manipulated by an external
      electric current.
AB  - Interfacial electron transfer (IET) dynamics in a 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindodicarbocyanine (DiD) dye molecule/indium tin oxide (ITO) film
      system have been probed at the ensemble and single-molecule levels. By comparing
      the difference in the external electric current (EEC) dependence of the
      fluorescence intensities and lifetimes of the ensembles and single molecules, it
      is shown that the single-molecule probe can effectively demonstrate IET dynamics.
      The backward electron transfer and electron transfer from the ground state induce
      single-molecule fluorescence quenching when an EEC is applied to the DiD/ITO film
      system.

PMID- 21738914
TI  - Molecular quadrangle formation from a diuranium MU-eta6,eta6-toluene complex.
AB  - A new inverted sandwich of a MU-eta(6),eta(6)-toluene diuranium complex reacted
      with quinoxaline to form a tetranuclear macrocycle with ferrocene diamide
      uranium(IV) vertices and reduced quinoxaline edges.

PMID- 21738915
TI  - Regio-selective decoration of nanocavity metal arrays: contributions from
      localized and delocalized plasmons to surface enhanced Raman spectroscopy.
AB  - Spherical cap gold nanocavity arrays with internal diameters of 240, 430, 600 and
      820 nm were fabricated on smooth gold films using nanosphere lithography with
      electrochemical metal deposition. Each array was prepared to the same normalized
      film thickness to diameter ratios, t(N), of 0.8 +/- 0.04. Selective modification
      of the top surface and interior walls of the gold nanocavity arrays with
      [Ru(bpy)(2)(Qbpy)](2+), where bpy is 2,2'-bipyridyl and Qbpy is 2,2':4,4'':4,4''
      quarterpyridyl, was accomplished using a two step adsorption process exploiting
      the assembled polystyrene spheres as masks. This selective modification approach
      permitted direct quantitative comparison, for the first time, of plasmonic
      enhancement of Raman signal and luminescence signal from a monolayer adsorbed at
      the top surface versus interior walls of all-gold nanocavity arrays. For all
      cavity sizes, significantly greater Raman and luminescence signal enhancement was
      observed from [Ru(bpy)(2)(Qbpy)](2+) monolayer adsorbed at the top surface of the
      array compared with the cavity walls. This disparity in Raman intensity from top
      versus cavity interior increased as the cavity dimensions decreased. For example,
      the Raman signal intensity from [Ru(bpy)(2)(Qbpy)](2+) adsorbed at the top
      surface of 240 nm gold arrays was 170 times greater than SERS signal for this
      material adsorbed at the interior walls of this array, whereas the relative Raman
      signal enhancement was 6 from top versus interior for the 820 nm internal radius
      arrays under 785 nm excitation. The origin of the relatively greater signal at
      the top surface is discussed in the context of plasmonic distribution at each
      surface.

PMID- 21738916
TI  - Bromopyridazinedione-mediated protein and peptide bioconjugation.
AB  - Bromopyridazinedione-mediated bioconjugation to a cysteine containing protein and
      a disulfide containing peptide is described. The conjugates are cleavable in an
      excess of thiol, including cytoplasmically-relevant concentrations of
      glutathione, and show a high level of hydrolytic stability. The constructs have
      the potential for four points of chemical attachment.

PMID- 21738917
TI  - TiO2-decorated graphene nanohybrids for fabricating an amperometric
      acetylcholinesterase biosensor.
AB  - This work describes a highly sensitive and rapid amperometric biosensor for
      organophosphate compounds (OPs) based on immobilization of acetylcholinesterase
      (AChE) on a novel TiO(2)-decorated graphene (TiO(2)-G) nanohybrid, which was
      constructed by in situ growth of TiO(2) nanoparticles (NPs) on the graphene
      sheet. The well-dispersed TiO(2) NPs eliminated the restacking of TiO(2)-G
      nanohybrids. Due to the integrating of TiO(2)-G nanohybrids, the as-prepared
      biosensor showed high affinity to acetylthiocholine (ATCl) with a Michaelis
      Menten constant (K(m)) value of 0.22 mM, and rapid inhibition time (3 min).
      Further, based on the inhibition of OPs on the enzymatic activity of the
      immobilized AChE, and using carbaryl as a model compound, the inhibition of
      carbaryl was proportional to its concentration ranging from 0.001 to 0.015 and
      0.015 to 2 MUg mL(-1) with a detection limit of 0.3 ng mL(-1) (S/N = 3). The
      developed biosensor exhibited a good performance for organophosphate pesticide
      detection, including good reproducibility and acceptable stability, which
      provided a new and promising tool for the analysis of enzyme inhibitors.

PMID- 21738918
TI  - Simple synthesis of 1,3-cyclopentanedione derived probes for labeling sulfenic
      acid proteins.
AB  - Facile, two-step synthesis and kinetic characterization of new chemical probes
      for selective labeling of sulfenic acid (-SOH) in proteins are presented. The
      synthesis route relies on the simple and highly efficient Michael addition of
      thiol containing tags or linkers to 4-cyclopentene-1,3-dione, the unsaturated
      derivative of 1,3-cyclopentanedione.

PMID- 21738919
TI  - Measuring rapid kinetics by a potentiometric method in droplet-based microfluidic
      devices.
AB  - Droplets containing RNA and Mg(2+) were generated in microfluidic channels. By
      integrating a group of pneumatic valves and phase separation channels in the
      microfluidic system, the rapid RNA-Mg(2+) binding kinetics was studied by
      measuring the Mg(2+) ion concentration using an ion-selective electrode.

PMID- 21738920
TI  - Molecular packing density of a self-assembled monolayer formed from N-(2
      aminoethyl)-3-aminopropyltriethoxysilane by a vapor phase process.
AB  - The molecular density of an aminosilane self-assembled monolayer formed from N-(2
      aminoethyl)-3-aminopropyltriethoxysilane (AEAPS) by a vapor phase method has been
      estimated to be about 3 AEAPS molecules per nm(2) based on chemical labeling,
      optical absorption spectroscopy and X-ray photoelectron spectroscopy.

PMID- 21738921
TI  - CN- scavenger: a leap towards development of a CN- antidote.
AB  - Compound 4 removes cyanide from water and human serum in the form of compound 7
      (cyano-derivative of 4) and experiments show its suitability as an antidote of
      CN(-) poisoning.

PMID- 21738922
TI  - A convenient method for the measurements of transverse relaxation rates in
      homonuclear scalar coupled spin systems.
AB  - A new solution-state NMR method is proposed to determine apparent transverse NMR
      relaxation rates in both weakly and strongly scalar coupled two-spin systems.

PMID- 21738923
TI  - Nickel(II) oxide surface-modified titanium(IV) dioxide as a visible-light-active
      photocatalyst.
AB  - The electronic modification of TiO(2) with highly dispersed NiO particles smaller
      than ca. 2 nm by the chemisorption-calcination-cycle technique has given rise to
      a high level of visible-light-activity exceeding that of iron oxide-surface
      modified TiO(2) simultaneously with the UV-light-activity being significantly
      increased.

PMID- 21738924
TI  - An uncommon highly oxidized multiple bonded Re2(8+) species.
AB  - A long-sought metal-metal bonded species with an M(2)(8+) core has been
      structurally characterized. The diamagnetic compound
      {[Re(2)(hpp)(3)(OH)(O(3)SCF(3))](2)(MU-O)(2)}(O(3)SCF(3))(2), 2, has two
      sigma(2)pi(4) electron-poor triple-bonded Re(2)(8+) units embraced by three
      bicyclic guanidinate ligands (hpp) and axial OH and triflate groups; the two
      dimetal units are held together by bridging oxo-groups.

PMID- 21738925
TI  - Thioether-phosphite: new ligands for the highly enantioselective Ir-catalyzed
      hydrogenation of minimally functionalized olefins.
AB  - We have described the first successful application of non-N-donor heterodonor
      ligands--thioether-phosphite ligands--in the Ir-catalyzed hydrogenation of
      minimally functionalized olefins. Excellent enantioselectivities (ee's up to 99%)
      have been obtained for a range of substrates, including challenging terminal
      disubstituted substrates, under standard conditions.

PMID- 21738926
TI  - Sortase A-catalyzed peptide cyclization for the synthesis of macrocyclic peptides
      and glycopeptides.
AB  - A chemoenzymatic method was developed for the synthesis of macrocyclic peptides
      and glycopeptides. Sortase A was found to mediate either head to tail cyclization
      or oligomerization and then head to tail cyclization of peptides and
      glycopeptides, depending on the peptide length, to produce 15-mer or higher
      cyclic peptides and glycopeptides.

PMID- 21738927
TI  - Mechanistic understanding of multistep assembly of DNA with a carbazole ligand by
      simple adjustment of host-guest concentrations.
AB  - Two alternative binding states are identified in interaction of calf thymus DNA
      with a partially hydrophobic carbazole ligand [(Im(+))(2)Cz], where biphasic UV
      vis and circular dichroic (CD) spectral changes are apparent during the titration
      of calf thymus DNA with the carbazole ligand.

PMID- 21738928
TI  - Pincer ligands with an all-phosphorus donor set: subtle differences between
      rhodium and palladium.
AB  - The synthesis of a new, all-phosphorus pincer PP(NEt2)P ligand L3(NEt2), which is
      derived from 2-indolylphosphine and features a central N(2)P(NEt(2)) core, is
      described. This 'PPP' species shows coordination toward Rh as a neutral
      trisphosphine ligand. Tridentate diphenylphosphine-derived PP(H)P ligands L1(H)
      and L2(H), featuring a secondary phosphine core, show 'ambivalent' coordination,
      acting as persistent neutral triphosphine ligands with Rh, and as easily-formed
      monoanionic phosphido(bisphosphine) pincer ligands toward Pd. These subtle
      differences, which might be more general for group 9 and 10 metal complexes with
      this ligand set, are explained by comparative DFT calculations (BP86; def2-TZVP
      level of theory) for the Rh and Pd species involved, including those with the
      structurally related PN(H)P ligands. The optimized structure for complex PdCl(L2)
      indicates minimal overlap of available Pd d-orbitals with the lone pair of the
      central, deprotonated phosphorus atom (formally a phosphido fragment), suggesting
      that it behaves predominantly like a bulky phosphine instead of a phosphido
      fragment.

PMID- 21738929
TI  - Further insight into the coordination of 2,5-dicarbothioamidopyrroles: the case
      of Cu and Co complexes.
AB  - The coordination chemistry of 2,5-dicarbothioamidopyrrole ligands, namely N2,N5
      dibutyl-3,4-diphenyl-1H-pyrrole-2,5-bis(carbothioamide) and N2,N5,3,4-tetraphenyl
      1H-pyrrole-2,5-bis(carbothioamide), has been investigated with Cu(II) metal
      centres by means of X-ray crystallography. This resulted in the formation of the
      expected planar S,N,S' coordinated complex for the former ligand and unexpected
      ring-closure reactions, with formation of benzothiazole sidearms, for the latter.
      Both Cu(II) and Cu(I), used in large excess, were found to favour the ring
      closure reaction, although the structural characterisation of the resulting
      complexes contained only Cu(II) cations, with varying coordination geometries
      ranging from square planar and square-based pyramidal to tetrahedral. By
      repeating the reaction using a slight excess of Cu(II) (2 : 1) two more different
      structures were obtained where the metal was coordinated to the original ligand,
      N2,N5,3,4-tetraphenyl-1H-pyrrole-2,5-bis(carbothioamide), or to the mixed ligand
      where only one of the thioamide substituents had converted to a benzothiazole.
      The essential role of Cu for the ring closure reaction was also established by
      comparing its complex with structural features of the analogous Co(II) complex,
      the latter revealing no ring closure to give benzothiazole substituents and co
      crystallisation of a mixed Co(II)/Co(III) complex. Finally, the structure and
      photophysical properties of the corresponding 3,4-diphenyl-2,5-bis(benzothiozol-5
      yl)-pyrrole ligand, obtained via treatment of the thioamide with K(3)[Fe(CN)(6)],
      were also investigated revealing a blue-centered emission.

PMID- 21738930
TI  - Natural products in anti-obesity therapy.

PMID- 21738931
TI  - Detection of mercury and phenylmercury ions using DNA-based fluorescent probe.
AB  - A DNA probe labeled with a 4-([4-(dimethylamino)phenyl]azo)benzoic acid (DABCYL)
      quencher and a carboxyfluorescein (FAM) donor at its 5'- and 3'-termini can be
      used for the detection of Hg(2+) ions and phenylmercury ions (PhHg(+)). This DNA
      probe possesses a random coil structure that changes into a hairpin-like
      structure upon binding Hg(2+) and PhHg(+) ions. As a result, the fluorescence of
      the FAM unit decreased through quenching between the donor and the quencher. In
      the presence of ethylenediaminetetraacetic acid (EDTA), the DNA probe allowed the
      selective detection of PhHg(+) ions at concentrations as low as 70.0 nM, mainly
      as a result of T-Hg(2+)-T coordination and pi-pi stacking between the Ph unit and
      DNA bases. A linear correlation existed between the fluorescence intensity and
      the concentration of PhHg(+) ions over the range from 0.10 to 1.0 MUM (R(2) =
      0.99). After acid hydrolysis and neutralization of the samples, all of the
      mercury species are converted to Hg(2+) ions, allowing us to use the DNA-based
      probe to determine the concentrations of total mercury species at the nM level.
      The practicality of this probe has been validated by the analyses of pond water
      and fish samples, showing its advantages of sensitivity, selectivity, and
      simplicity.

PMID- 21738932
TI  - Detecting DNA targets through the formation of DNA/CTAB complex and its
      interactions with liquid crystals.
AB  - In this paper, we report the formation of a DNA/cetyl trimethylammonium bromide
      (CTAB) complex on a solid surface and its interaction with a thin layer of liquid
      crystals (LC) supported on the surface. Our results show that when the surface is
      decorated with DNA only, the LC gives a bright image, but when the surface is
      decorated with the DNA/CTAB complex, the LC becomes dark when the surface density
      of CTAB is above 5.25 +/- 0.13 * 10(13)/cm(2). To exploit this phenomenon for
      detecting DNA targets, we used a surface decorated with electroneutral PNA probes
      for capturing DNA targets, and then treated the surface with 0.1 mM of CTAB. In
      the presence of DNA targets, a PNA/DNA/CTAB complex is formed and that leads to a
      dark image on the thin layer of the LC supported on the surface. Moreover, DNA
      targets with a complementary, 1-base mismatch and non-complementary sequence can
      be differentiated by using this method. This study provides a new principle for
      the label-free detection of DNA targets without any fluorescent labels.

PMID- 21738933
TI  - Vapour-adsorption and chromic behaviours of luminescent coordination polymers
      composed of a Pt(II)-diimine metalloligand and alkaline-earth metal ions.
AB  - Four new bimetallic coordination polymers (CPs), {M[Pt(CN)(2)(5,5'
      dcbpy)].4H(2)O}(n) (M = Mg(2+), Ca(2+), Sr(2+), Ba(2+); 5,5'-H(2)dcbpy = 5,5'
      dicarboxy-2,2'-bipyridine) were synthesized using four alkaline-earth metal ions
      and a Pt(II)-diimine metalloligand [Pt(CN)(2)(5,5'-H(2)dcbpy)]. All four CPs are
      isomorphous with the Zn complex, {Zn[Pt(CN)(2)(5,5'-dcbpy)].4H(2)O}(n), which
      exhibits effective metallophilic interactions between Pt(II) ions. These CPs
      exhibited colourful thermochromic behaviour and solid-state solvatochromic-like
      behaviours when suspended in various solvents. Thermogravimetric analysis and
      vapour-adsorption measurements revealed that the CPs can reversibly adsorb water
      and MeOH vapours. The emission energy of the triplet metal-metal-to-ligand charge
      transfer ((3)MMLCT) state varied markedly upon guest adsorption/desorption. The
      chromic and vapour-adsorption properties of these CPs depend strongly on the
      cross-linking M(2+) ions.

PMID- 21738934
TI  - A DFT comparison of the neutral and cationic Heck pathways.
AB  - The two distinct mechanistic pathways of the Heck reaction, cationic and neutral,
      are characterized computationally using DFT calculations with corrections for
      solvation and dispersion. The selectivity in each type of reaction is discussed
      in terms of the detailed reaction paths, and the two types are compared to each
      other. The geometries and energies of the selectivity-determining transitions
      states are analyzed in detail.

PMID- 21738935
TI  - Coupling reaction between electron-rich pyrimidinones and alpha-amino acids
      promoted by phosphonium salts.
AB  - Coupling reaction between electron-rich 2-morpholino-4(3H)-pyrimidinone and
      nucleophilic side chains of several natural alpha-amino acids promoted by
      phosphonium salt has been developed to prepare new optically active pyrimidin-4
      yl amino acids. The best results were obtained using a two-step method through
      the easily available benzotriazolyl-1-oxy intermediate. A detailed optimization
      study of this reaction is discussed.

PMID- 21738936
TI  - Photopatterning of ultrathin electrochemiluminescent redox hydrogel films.
AB  - Photoinitiated polymerisation is efficiently and rapidly carried out to
      immobilise ultrathin electrochemiluminescent redox hydrogel films. Microscale
      patterns are fabricated on an electrode surface by a simple photolithographic
      procedure and revealed by ECL imaging.

PMID- 21738937
TI  - Occurrence and exposure assessment of perchlorate, iodide and nitrate ions from
      dairy milk and water in Japan and Sri Lanka.
AB  - Perchlorate is known to competitively interfere with iodide uptake by the thyroid
      gland and thereby human exposure to perchlorate is a public health concern.
      Prevalence of perchlorate in dairy milk is documented; nevertheless, co
      occurrence of perchlorate with other thyroid-binding monovalent ions such as
      iodide and nitrate is not well understood. In this study, we analyzed
      perchlorate, iodide, and nitrate-N in dairy milk, water and other dairy-related
      samples collected from Japan and Sri Lanka. Concentrations of perchlorate in
      Japanese dairy milk samples ranged from 1.03 to 14.1 ng ml(-1); the corresponding
      concentrations in dairy milk and powdered milk from Sri Lanka were 1.14-38.5 ng
      ml(-1). Perchlorate concentrations in commercial milk were significantly higher
      in Japan than in Sri Lanka, while iodide and nitrate levels in milk between the
      two countries were comparable. All three ions were ubiquitously found in water
      samples from Japan and Sri Lanka. Analysis of colostrum and raw milk collected
      from cows fed with the same feed for over 30 days showed no significant temporal
      variations in perchlorate, iodide and nitrate-N concentrations. A significant
      positive correlation was found between the concentrations of perchlorate and
      iodide in Japanese commercial milk. The concentrations of perchlorate and nitrate
      N in water samples analyzed from both countries also showed a significant
      positive correlation. The exposure estimation revealed that dairy milk provides a
      greater source for perchlorate and iodide, while water predominantly contributes
      nitrate-N intake for all age groups in both counties. Infants and children
      demonstrated the highest estimated perchlorate, iodide and nitrate-N intake on a
      body weight basis in comparison to other age groups. Therefore, further studies
      of risk associated with perchlorate may need to reconsider co-existence of iodine
      and other iodide transport inhibitors in food.

PMID- 21738938
TI  - Preparation and evaluation of a phenylboronate affinity monolith for selective
      capture of glycoproteins by capillary liquid chromatography.
AB  - A phenylboronate affinity monolith was prepared and applied to the selective
      capture of glycoproteins from unfractionated protein mixtures. The monolith was
      synthesized in a 100 MUm i.d capillary by an in situ polymerization procedure
      using a pre-polymerization mixture consisting of 4-vinylphenylboronic acid (VPBA)
      as functional monomer, ethylene dimethacrylate (EDMA) as crosslinker, diethylene
      glycol and ethylene glycol as binary porogenic solvents, and
      azobisisobutyronitrile (AIBN) as initiator. The prepared monolith was
      characterized in terms of the morphology, pore property, and recognition
      property. The selectivity and dynamic binding capacity were evaluated by using
      standard glycoproteins and nonglycoproteins as model proteins. The
      chromatographic results demonstrated that the phenylboronate affinity monolith
      had higher selectivity and binding capacity for glycoprotein than
      nonglycoprotein. The resulting phenylboronate affinity monolith was used as the
      sorbent for in-tube solid phase microextraction (in-tube SPME), and the
      extraction performance of the monolith was assessed by capture of ovalbumin from
      egg white sample.

PMID- 21738939
TI  - Thermal lens detection device.
AB  - A thermal lens detection device was developed to realize an easy-to-use, portable
      and sensitive detector for nonfluorescent molecules. Two laser diodes (658 nm for
      excitation and 785 nm for probe) were made coaxial in an optical unit and were
      coupled to a single-mode optical fiber. On a microfluidic chip, a small holder
      for the optical fiber was fixed, and micro-lenses (numerical aperture of 0.2)
      were also integrated inside the holder. The micro-lenses were designed to realize
      an adequate chromatic aberration (50 MUm), which was essential for sensitive
      thermal lens detection. Compared with conventional thermal lens detection systems
      which required very laborious and accurate optical alignment with the
      microchannel, the new device needed just attachment-detachment of the optical
      fiber, which was important for practical application. The lower limit of
      detection was 10 nM for nickel(II) phthalocyaninetetrasulfonic acid tetrasodium
      salt solutions (model sample), and the absorbance was 9 * 10(-6) AU. The absolute
      number of molecules detected was less than 200 zmol. The coefficient of variance
      for 5-time attachment-detachment of the optical probe was as small as 3.6%. The
      technical development allowed integration of the thermal lens detection devices
      inside a microsystem (e.g. enzyme-linked immuno-sorbent assay system), and
      practical microsystems were realized with sensitivities several-orders higher
      than absorptiometry.

PMID- 21738940
TI  - Printed two-dimensional micro-zone plates for chemical analysis and ELISA.
AB  - In this study we report a new concept of printing low-cost two-dimensional micro
      zone plates for chemical and biochemical assays and ELISA. It is different from
      the concept of forming multi-zone micro-zones on paper by hydrophobic barriers
      first reported by Yagoda. Instead, the desired multi-zone micro-zone pattern was
      first printed using a UV-curable varnish onto a polymer film; then fine powders
      of cellulose or other materials were applied onto the uncured varnish, allowing
      the powder to stick to the varnish layer. After UV-curing, the powder particles
      were fixed by the cured varnish, leading to the formation of porous, water
      absorbing micro-zones on the polymer film. This type of micro-zone plate has the
      required liquid handling capacity for a variety of low-volume and portable two
      dimensional plates for chemical, biochemical assays and ELISA. By suitably
      spacing porous micro-zones on a non-porous substrate, this type of plate
      eliminates inter-zone sample leaking. Rapid colorimetric analysis of the results
      can be performed using a portable battery-powered colour densitometer or a
      desktop scanner. By introducing a refractive-index-matching liquid into the micro
      zones, the plate can be easily analyzed using transmission instruments. A major
      advantage of this plate fabrication method is that it enables the printing of
      different powders or functionalized powders to form micro-zones on a same plate,
      potentially allowing certain more difficult functionalization of materials to be
      performed before printing. We demonstrate the assaying performance of the plates
      using an analytical system that aims to clarify the analytical interference
      between NO(2)(-) and uric acid (UA) in the analysis of samples where both
      chemical species are present. We also show that ELISA assays can be performed
      using this type of plates.

PMID- 21738941
TI  - The role of disorder on the electronic structure of conjugated polymers. The case
      of poly-2,5-bis(phenylethynyl)-1,3,4-thiadiazole.
AB  - Insight into the electronic structure of disordered poly-2,5-bis(phenylethynyl)
      1,3,4-thiadiazole in an amorphous region, in comparison to an ideal two-planar
      cofacial oligomer system, is pursued. The atomic structure of the amorphous
      polymer was obtained from classical molecular dynamics. It was subsequently used
      to calculate the electronic states and inter- and intrachain electronic coupling
      integrals using the density functional theory based charge patching method. The
      interchain electronic coupling integrals in the amorphous system were found to be
      an order of magnitude smaller than in the ordered system with similar distances
      between the chains. The results also suggest that the electronic structure of the
      whole system cannot be understood as a collection of the electronic structures of
      individual chains. The band gap of the whole system is significantly smaller than
      the band gaps of individual chains. This decrease originates from the disordered
      long range electrostatic potential created by the dipole moments of polymer
      repeat units, which should be minimized if one seeks good transport properties.

PMID- 21738942
TI  - Probing the electronic and optical properties of silica-coated quantum dots with
      first-principles calculations.
AB  - The electronic and optical natures of silica-coated semiconductor nanocrystals
      (Cd(2)Te(2)@(SiO(2))(24)) have been investigated by density functional theory
      (DFT) and time-dependent DFT calculations. The calculated results of
      Cd(2)Te(2)@(SiO(2))(24) have revealed that the structural synergy effect between
      the Cd(2)Te(2) quantum dots (QDs) and the silica coating shell plays a dominant
      role in the photoelectric properties. The binding of embedded Cd(2)Te(2) to the
      outer silica coating shell leads to the distortion of the silica nanocage,
      indicating strong coupling between the QDs and silica shell. The optical features
      of Cd(2)Te(2) clusters and Cd(2)Te(2)@(SiO(2))(24) complexes were evaluated using
      the time-dependent DFT method. It is determined that the maximal absorption peak
      of isolated Cd(2)Te(2) in a UV-Vis absorption spectrum appears at 584 nm, which
      shifts to 534 nm when the Cd(2)Te(2) QDs were encapsulated by silica, in close
      agreement with the experimental evidence. The excited process has a direct
      electronic transition character from the occupied Cd(2)Te(2) states to the outer
      silica nanocage excited states (core -> shell electronic transitions). A deep
      insight into silica-coated QD systems is beneficial for understanding their
      optical nature and the development of core/shell QDs.

PMID- 21738943
TI  - Assessing disproportionate costs to achieve good ecological status of water
      bodies in a Mediterranean river basin.
AB  - Water management is becoming increasingly important as the demand for water
      grows, diversifies, and includes more complex environmental concerns. The Water
      Framework Directive (WFD) seeks to achieve a good ecological status for all
      European Community water bodies by 2015. To achieve this objective, economic
      consideration of water management must be given to all decision-making processes.
      Exemption (time or level of stringency) from the objectives of the EU Directive
      can be justified by proving that the cost of implementing measures is
      disproportionate to the benefits. This paper addresses the issue of
      disproportionate costs through a cost-benefit analysis (CBA). To predict the
      costs, the function costs method is used. The quantification of environmental
      benefits is more complex, because they are not determined by the market. As an
      alternative to stated preference methods, we use the distance function approach
      to estimate the environmental benefits of improving water quality. We then apply
      this methodological approach to a Mediterranean River Basin in Spain. The results
      show that the achievement of good status could not be rejected based on the
      criterion of disproportionate costs in this river basin. This paper illustrates
      that CBA is a useful tool to inform policy and decision making. Furthermore, it
      is shown that economics, particularly the valuation of environmental benefits,
      plays a crucial role in fulfilling the environmental objectives of the WFD.

PMID- 21738944
TI  - How many trimers? Modeling influenza virus fusion yields a minimum aggregate size
      of six trimers, three of which are fusogenic.
AB  - Conflicting reports in leading journals have indicated the minimum number of
      influenza hemagglutinin (HA) trimers required for fusion to be between one and
      eight. Interestingly, the data in these reports are either almost identical, or
      can be transformed to be directly comparable. Different statistical or
      phenomenological models, however, were used to analyze these data, resulting in
      the varied interpretations. In an attempt to resolve this contradiction, we use
      PABM, a brane calculus we recently introduced, enabling an algorithmic systems
      biology approach that allows the problem to be modeled in a manner following a
      biological logic. Since a scalable PABM executor is still under development, we
      sufficiently simplified the fusion model and analyzed it using the model checker,
      PRISM. We validated the model against older HA-expressing cell-to-cell fusion
      data using the same parameters with the exception of three, namely HA and sialic
      acid (SA) surface densities and the aggregation rate, which were expected to be
      different as a result of the difference in the experimental setup. Results are
      consistent with the interpretation that a minimum aggregate size of six HA
      trimers, of which three undergo a conformational change to become fusogenic, is
      required for fusion. Of these three, two are free, while one is bound. Finally,
      we determined the effects of varying the SA surface density and showed that only
      a limited range of densities permit fusion. Our results demonstrate the potential
      of modeling in providing more precise interpretations of data.

PMID- 21738945
TI  - Changes in maternal blood concentrations of selected essential and toxic elements
      during and after pregnancy.
AB  - The objective of this study was to investigate changes in the levels of toxic and
      essential elements in maternal blood during pregnancy and subsequently. A subset
      of 211 pregnant women from the North Norwegian Mother-and-Child Study was
      included. Blood samples were collected during the 2(nd) trimester (P1) and
      postpartum (day 3, P2; and 6 weeks, P3) in different regions of northern Norway,
      and were analyzed for a suite of 10 selected elements. The latter feature three
      general but distinct concentration patterns across the three collection periods,
      namely: progressive increase [Group 1: As, Cd (non-smokers only), Mn, Pb and Zn];
      V-shaped, with a minimum at P2 [Group 2: Cd (smokers), Hg, Mo and Se]; and
      downward V, with a maximum at P2 [Group 3: Co and Cu]. These trends are
      interpreted in the context of underlying metabolic, hematological and
      physiological changes that occur in mothers, as well the biochemistry and
      accumulation preferences of these elements within the whole blood compartment and
      breast milk. Implications for biomonitoring strategies are discussed. In a
      multivariable analysis of the P1 data, fish consumption was a robust positive
      predictor for Hg (p < 0.02), As (p < 0.01) and Se (p <= 0.001) blood
      concentrations, multivitamin intake for Se (p < 0.001), and parity for Co (p <
      0.002); age reached significance only for Hg (p < 0.001). An inverse association
      was observed between parity and Hg (p < 0.05). For the other elements, predictor
      patterns were not evident.

PMID- 21738946
TI  - Micropatterns of double-layered nanofiber scaffolds with dual functions of cell
      patterning and metabolite detection.
AB  - This paper describes the development of multi-functional nanofiber scaffolds
      consisting of multiple layers of nanofiber scaffolds and nanofiber-incorporated
      poly(ethylene glycol) (PEG) hydrogels. As a proof-of-concept demonstration, we
      fabricated micropatterned polymeric nanofiber scaffolds that were capable of
      simultaneously generating cellular micropatterns within a biomimetic environment
      and detecting cellular metabolic products within well-defined microdomains. To
      achieve this goal, we designed nanofiber scaffolds with both vertical and lateral
      microdomains. Vertically heterogeneous structures that were responsible for multi
      functionality were realized by preparing double-layered nanofiber scaffolds
      consisting of an antibody-immobilized bottom layer of nanofibers and an upper
      layer of bare polystyrene (PS) nanofibers by a two-step sequential
      electrospinning process. Photopatterning of poly(ethylene glycol) (PEG) hydrogel
      on the electrospun nanofibers produced laterally heterogeneous micropatterned
      nanofiber scaffolds made of hydrogel microwells filled with a nanofibrous region,
      which is capable of generating cell and protein micropatterns due to the
      different interactions that cells and proteins have with PEG hydrogels and
      nanofibers. When HepG2 cells were seeded into resultant nanofiber scaffolds,
      cells selectively adhered within the 200 MUm * 200 MUm PS fiber microdomain and
      formed 180.2 +/- 6.7 MUm spheroids after 5 days of culture in the upper layer.
      Furthermore, immobilized anti-albumin in the bottom layer detected albumin
      secreted by micropatterned HepG2 cells with higher sensitivity than flat PS
      substrates, demonstrating successful accomplishment of dual functions using
      micropatterned double-layered nanofiber scaffolds.

PMID- 21738947
TI  - Ligand-free palladium-catalyzed intramolecular Heck reaction of secondary
      benzylic bromides.
AB  - A facile ligand-free palladium-catalyzed intramolecular Heck reaction of beta
      hydrogen-containing secondary benzylic bromides was developed, which affords
      pyrroline derivatives with good regioselectivities.

PMID- 21738948
TI  - Synthesis of fused multicyclic compounds containing macrocycles by dienyne ring
      closing metathesis and Diels-Alder reactions.
AB  - Fused bicyclic compounds comprising small and large rings were synthesised by
      dienyne ring-closing metathesis (RCM) using Grubbs' catalyst. By taking advantage
      of faster small ring cyclisation compared with macrocyclisation, single isomers
      were obtained rather than mixtures of two isomers with different ring sizes.
      Using this process, various fused bicyclic compounds comprising small rings (5-7-
      membered) and large rings (14-17- membered) were obtained. By increasing reaction
      temperature and catalyst loading, the product conversion was improved in a
      predicted manner. This method produced E-olefins on the macrocycles with high
      selectivity. Also, the selectivity issues of tandem RCM for the synthesis of
      fused bicyclic compounds comprising small and medium rings were investigated.
      Lastly, the prepared bicyclic compounds with small and large rings contained 1, 3
      dienes that underwent a further modification reaction, such as Diels-Alder, to
      produce more complex compounds. These Diels-Alder reactions produced tri- and
      tetracyclic compounds containing a macrocycle with single diastereomers,
      suggesting that the methodology demonstrated here could be a powerful tool for
      rapid preparation of highly complex molecules.

PMID- 21738949
TI  - Interaction of thorium(IV) with nitrate in aqueous solution: medium effect or
      weak complexation?
AB  - Microcalorimetric titrations were performed to study the Th(IV)/nitrate
      interaction in aqueous solution. The results show the formation of a weak
      mononuclear complex of Th(IV) with nitrate and allow the determination of the
      complexation thermodynamic parameters at 298 K and ionic strength 1.0 mol dm(-3).
      The reaction is endothermic and entropy driven. Data and comparison with similar
      actinide(IV) complexes allow to confirm the inner-sphere nature of the
      Th(NO(3))(3+) complex.

PMID- 21738950
TI  - Increased levels of calprotectin in obesity are related to macrophage content:
      impact on inflammation and effect of weight loss.
AB  - Calprotectin has been recently described as a novel marker of obesity. The aim of
      this study was to determine the circulating concentrations and expression levels
      of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT),
      exploring its impact on insulin resistance and inflammation and the effect of
      weight loss. We included 53 subjects in the study. Gene expression levels of the
      S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and
      stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and
      soluble receptor for the advanced glycation end product (sRAGE) concentrations
      were measured before and after weight loss achieved by Roux-en-Y gastric bypass
      (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9
      complex were increased in normoglycemic and type 2 diabetic obese patients (P <
      0.01) and associated with markers of inflammation (P < 0.01). Oppositely,
      concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups
      compared to lean volunteers. Elevated calprotectin levels in obese patients
      decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to
      increase. Calprotectin was mainly expressed by SVFCs, and its expression was
      significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage
      related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic
      protein 1 (MCP1), integrin alpha-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor
      necrosis factor-alpha treatment significantly enhanced (P < 0.05) the mRNA levels
      of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The
      increased levels of calprotectin in obesity and obesity-associated type 2
      diabetes, its positive association with inflammation as well as the higher
      expression levels in the SVFCs in VAT suggests a potential role of this protein
      as a chemotactic factor in the recruitment of macrophages to VAT, increasing
      inflammation and the development of obesity-associated comorbidities.

PMID- 21738951
TI  - H3K27me3 protein is a promising predictive biomarker of patients' survival and
      chemoradioresistance in human nasopharyngeal carcinoma.
AB  - Trimethylation of lysine 27 on histone H3 (H3K27me3) is an epigenetic change
      which plays a critical role in tumor development and/or progression. However, the
      molecular status of H3K27me3 and its clinicopathologic/prognostic significance in
      nasopharyngeal carcinoma (NPC) have not been elucidated. In this study, the
      methods of Western blotting and immunohistochemistry (IHC) were utilized to
      examine the expression of H3K27me3 protein in NPC tissues and nonneoplastic
      nasopharyngeal epithelial tissues. Receiver operating characteristic (ROC) curve
      analysis was used to determine the cutpoint for H3K27me3 high expression. High
      expression of H3K27me3 could be observed in 127/209 (60.8%) of NPCs and in 8/50
      (16.0%) normal nasopharyngeal epithelial tissues (P < 0.001). Further correlation
      analysis demonstrated that high expression of H3K27me3 was positively associated
      with tumor later T classification, tumor metastasis, advanced clinical stage and
      chemoradioresistance (P < 0.05). Moreover, high expression of H3K27me3 was
      closely associated with NPC patient shortened survival time as evidenced by
      univariate and multivariate analysis (P < 0.05). Consequently, a new
      clinicopathologic prognostic model with three poor prognostic factors (H3K27me3
      expression, distant metastasis and treatment regimen) was constructed. The model
      could stratify risk significantly (low, intermediate and high) for overall
      survival and progression-free survival (P < 0.0001). These findings provide
      evidence that H3K27me3 expression, as examined by IHC, has the potential to be
      used as an immunomarker to predict NPC chemoradiotherapy response and patient
      prognosis. The combined clinicopathologic prognostic model may become a useful
      tool for identifying NPC patients with different clinical outcomes.

PMID- 21738952
TI  - The influence of developmental age on the early transcriptomic response of
      children with septic shock.
AB  - Septic shock is a frequent and costly problem among patients in the pediatric
      intensive care unit (PICU) and is associated with high mortality and devastating
      survivor morbidity. Genome-wide expression patterns can provide molecular
      granularity of the host response and offer insight into why large variations in
      outcomes exist. We derived whole-blood genome-wide expression patterns within 24
      h of PICU admission from children with septic shock. We compared the
      transcriptome between septic shock developmental-age groups defined as neonates
      (<= 28 d, n = 17), infants (1 month to 1 year, n = 62), toddlers (2-5 years, n =
      54) and school-age (>= 6 years, n = 47) and age-matched controls. Direct
      intergroup comparisons demonstrated profound changes in neonates, relative to
      older children. Neonates with septic shock demonstrated reduced expression of
      genes representing key pathways of innate and adaptive immunity. In contrast to
      the largely upregulated transcriptome in all other groups, neonates exhibited a
      predominantly downregulated transcriptome when compared with controls. Neonates
      and school-age subjects had the most uniquely regulated genes relative to
      controls. Age-specific studies of the host response are necessary to identify
      developmentally relevant translational opportunities that may lead to improved
      sepsis outcomes.

PMID- 21738953
TI  - Galantamine alleviates inflammation and other obesity-associated complications in
      high-fat diet-fed mice.
AB  - Obesity, a serious and growing health threat, is associated with low-grade
      inflammation that plays a role in mediating its adverse consequences. Previously,
      we have discovered a role for neural cholinergic signaling in controlling
      inflammation, and demonstrated that the cholinergic agent galantamine suppresses
      excessive proinflammatory cytokine release. The main objective of this study was
      to examine the efficacy of galantamine, a clinically-approved drug, in
      alleviating obesity-related inflammation and associated complications. After 8
      wks on a high-fat diet, C57BL/6J mice were treated with either galantamine (4
      mg/kg, intraperitoneally [i.p.]) or saline for 4 wks in parallel with mice on a
      low-fat diet and treated with saline. Galantamine treatment of obese mice
      significantly reduced body weight, food intake, abdominal adiposity, plasma
      cytokine and adipokine levels, and significantly improved blood glucose, insulin
      resistance and hepatic steatosis. In addition, galantamine alleviated impaired
      insulin sensitivity and glucose intolerance significantly. These results indicate
      a previously unrecognized potential of galantamine in alleviating obesity,
      inflammation and other obesity-related complications in mice. These findings are
      of interest for studying the efficacy of this clinically-approved drug in the
      context of human obesity and metabolic syndrome.

PMID- 21738954
TI  - Angiopoietin-1 protects heart against ischemia/reperfusion injury through VE
      cadherin dephosphorylation and myocardiac integrin-beta1/ERK/caspase-9
      phosphorylation cascade.
AB  - Early reperfusion after myocardial ischemia that is essential for tissue salvage
      also causes myocardial and vascular injury. Cardioprotection during reperfusion
      therapy is an essential aspect of treating myocardial infarction. Angiopoietin-1
      is an endothelial-specific angiogenic factor. The potential effects of
      angiopoietin-1 on cardiomyocytes and vascular cells undergoing reperfusion have
      not been investigated. We propose a protective mechanism whereby angiopoietin-1
      increases the integrity of the endothelial lining and exerts a direct survival
      effect on cardiomyocytes under myocardial ischemia followed by reperfusion.
      First, we found that angiopoietin-1 prevents vascular leakage through regulating
      vascular endothelial (VE)-cadherin phosphorylation. The membrane expression of VE
      cadherin was markedly decreased on hypoxia/reoxygenation but was restored by
      angiopoietin-1 treatment. Interestingly, these effects were mediated by the
      facilitated binding between SH2 domain-containing tyrosine phosphatase (SHP2) or
      receptor protein tyrosine phosphatase MU (PTPMU) and VE-cadherin, leading to
      dephosphorylation of VE-cadherin. siRNA against SHP2 or PTPMU abolished the
      effect of angiopoietin-1 on VE-cadherin dephosphorylation and thereby decreased
      levels of membrane-localized VE-cadherin. Second, we found that angiopoietin-1
      prevented cardiomyocyte death, although cardiomyocytes lack the angiopoietin-1
      receptor Tie2. Angiopoietin-1 increased cardiomyocyte survival through integrin
      beta1-mediated extracellular signal-regulated kinase (ERK) phosphorylation, which
      inhibited caspase-9 through phosphorylation at Thr125 and subsequently reduced
      active caspase-3. Neutralizing antibody against integrin-beta1 blocked these
      protective effects. In a mouse myocardial ischemia/reperfusion model,
      angiopoietin-1 enhanced cardiac function and reduction in left ventricular-end
      systolic dimension (LV-ESD) and left ventricular-end diastolic dimension (LV-EDD)
      with an increase in ejection fraction (EF) and fractional shortening (FS). Our
      findings suggest the novel cardioprotective mechanisms of angiopoietin-1 that are
      achieved by reducing both vascular leakage and cardiomyocyte death after
      ischemia/reperfusion injury.

PMID- 21738956
TI  - Immunopathology of allergic contact dermatitis.
AB  - Allergic contact dermatitis is the consequence of an immune reaction mediated by
      T cells against low molecular weight chemicals known as haptens. It is a common
      condition that occurs in all races and age groups and affects the quality of life
      of those who present it. The immunological mechanism of this disease has been
      reviewed in recent decades with significant advance in its understanding. The
      metabolism and pathway of the haptens as well as the activation and mechanism of
      action of the cells responsible for both the immune reaction and its completion
      are discussed in this article.

PMID- 21738955
TI  - Potential role of leptin, adiponectin and three novel adipokines--visfatin,
      chemerin and vaspin--in chronic hepatitis.
AB  - Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some
      factors associated with rapid progression have been identified. Steatosis,
      independently of its metabolic or viral origin, leads to liver injury and
      fibrosis. It is suggested that hepatitis C virus may contribute to a wide
      spectrum of metabolic disturbances-namely, steatosis, insulin resistance,
      increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus and
      lipid metabolism abnormalities. Adipokines, which are produced mainly by adipose
      tissue, may influence the inflammatory response and insulin sensitivity and
      contribute to the development of metabolic abnormalities in CHC and also regulate
      fibrogenesis and angiogenesis. Visfatin was described as an adipokine with
      immunomodulating and proinflammatory properties that promotes B-cell maturation
      and enhances activation of leukocytes, synthesis of adhesion molecules and
      production of proinflammatory cytokines. Visfatin exerts insulin-mimetic effects,
      decreases plasma glucose levels and regulates cell energy balance. Chemerin
      stimulates chemotaxis of dendritic cells, macrophages and natural killer (NK)
      cells toward the site of inflammation. On the other hand, it inhibits synthesis
      of proinflammatory mediators and enhances adiponectin production, influences
      adipocyte differentiation and maturation and regulates glucose uptake in
      adipocytes. Vaspin expression in human adipose tissue seems to be a compensatory
      mechanism associated with obesity and insulin resistance. Vaspin suppresses
      leptin, tumor necrosis factor (TNF)-alpha and resistin expression. Leptin
      protects against liver steatosis but accelerates fibrosis progression and
      exacerbates the inflammatory process. In contrast, adiponectin exerts a
      hepatoprotective effect. In this report, data indicating a possible role of these
      adipokines in the pathogenesis of chronic hepatitis are summarized.

PMID- 21738957
TI  - Breastfeeding and mucosal and cutaneous colonization by Staphylococcus aureus in
      atopic children.
AB  - BACKGROUND: Studies on the effects of breastfeeding on the development of Atopic
      Dermatitis (AD) have shown controversial results. The importance of this
      condition deserves further studies; in particular, it remains unclear whether
      colonization of atopic patients by Staphylococcus aureus (S. aureus) through
      breastfeeding is relevant to the development of AD. OBJECTIVE: To examine the
      potential relation between breastfeeding and colonization by S. aureus in atopic
      patients. METHOD: Transversal study of atopic patients, aged from 4 to 24 months,
      both genders, receiving outpatient care and 72 mothers. Data on infant
      breastfeeding practices and on clinical-epidemiological profile were registered.
      Swabs of the infants' nares and skin (cubital fossa) and swabs of the mothers'
      nares were collected. For univariate analysis, X2 (chi-square) and Fischer
      Exact's test were used. RESULTS: Among breastfed children, S. aureus was isolated
      from 8 (25.8%) infants' nares swabs and from 4 (12.9%) skin swabs. Among not
      breastfed children, S. aureus was isolated from 10 (20.8%) infants' nares swabs
      and from 11 (22.9%) skin swabs. Sixteen mothers (22.2%) had S. aureus isolated
      from their nares swabs. There was no significant association between
      breastfeeding and S. aureus colonization (child skin and/or nares). However,
      there was a degree of concordance for S. aureus carriage among mothers and
      infants. Among 72 pairs, 56 (77.8%) were concordant. CONCLUSION: Breastfeeding
      was not associated with S. aureus muco-cutaneous colonization in atopic infants.

PMID- 21738958
TI  - Cryopeeling for treatment of photodamage and actinic keratosis: liquid nitrogen
      versus portable system.
AB  - BACKGROUND: Cryopelling uses diffuse cryotherapy not only on lesions of actinic
      keratosis but all over the photodamaged skin. OBJECTIVES: The aim of this study
      was to compare two cryopeeling methods (liquid nitrogen- LN and portable system -
      PS) and demonstrate their efficiency in the treatment of actinic keratoses,
      patient tolerance, researcher and patient preference and aesthetic results.
      METHODS: Sixteen patients (N = 16) with multiple actinic keratoses on the
      forearms were subjected to cryopeeling with LN on one of the forearms and PS on
      the other, randomly. RESULTS: In the treatment of actinic keratoses, LN obtained
      74% efficiency and PS, 62% (p = 0.019). The mean visual analogue scale (0-10) was
      5.7 +/- 1.61 with LN and 4.3 +/- 1.44 with PS (p = 0.003). There was no
      significant statistical difference between the two methods in terms of researcher
      and patient preference. An analysis of the photos showed improvement of the skin
      appearance with both treatments (p <0.001). Treatment with LN obtained some
      degree of improvement in 62.5% of the cases, while treatment with PS obtained
      some degree of improvement in 52% of the cases (p> 0.05). DISCUSSION: Treatment
      with the PS showed better tolerance, but was less efficient than LN. Although LN
      has been the preferred method, there was no statistical difference between the
      methods. CONCLUSIONS: The cryopeeling technique may be an option in the treatment
      of photodamage. The PS can be an interesting alternative in clinical practice
      with good tolerance and acceptable results in the treatment of actinic keratoses.

PMID- 21738959
TI  - Habits related to sun exposure among physical education teachers working with
      water activities.
AB  - BACKGROUND: Ultraviolet radiation has been considered one of the most important
      risk factors for melanoma or nonmelanoma skin cancer. Thus, it has been accepted
      that professionals working with outdoor activities are at greater risk of
      developing skin cancer. OBJECTIVE: To identify sun-exposure habits among teachers
      of physical education (PE) who work with water activities. METHODS: We conducted
      an observational cross-sectional study with 123 male and female PE teachers aged
      between 20 and 58 years who have been working with water activities for at least
      a year using a questionnaire with open and closed-ended questions. RESULTS: Of
      the respondents, it was observed that 64.2% work directly exposed to the sun and
      13.0% in partially covered pools; out of these, 69.5% do so between 10 am and 4
      pm. In the group exposed to the sun, it was found that only 17.9% always protect
      themselves. Men seem to be less careful, since 14.3% always protect themselves,
      while 23.1% of the women reported to always protect themselves. However, there
      were no statistically significant differences. CONCLUSION: Based on the data
      collected, we conclude that the sample investigated may be at risk of developing
      skin cancer.

PMID- 21738960
TI  - The use of oxybutynin for treating facial hyperhidrosis.
AB  - BACKGROUND: Facial hyperhidrosis is a disease that may lead patients to serious
      emotional disturbances. Video-assisted thoracic sympathectomy provides excellent
      resolution of facial hyperhidrosis, but is associated with certain complications.
      The most frequent and important complication is compensatory hyperhidrosis.
      Especially in patients who have undergone resection of the second thoracic
      ganglion, the risk of severe compensatory hyperhidrosis is higher, which may
      cause dissatisfaction with the procedure. OBJECTIVE: The aim of this study was to
      evaluate the efficacy of the use of low doses of oxybutynin in treating facial
      hyperhidrosis as well as the level of patient satisfaction with its use. METHODS:
      25 patients with facial hyperhidrosis were treated with oxybutynin. The patients
      underwent 2 evaluations: before and after treatment. These evaluations were used
      to assess the patients' clinical improvement and quality of life. RESULTS: We
      observed that more than 75% of the patients evolved with an improvement in facial
      hyperhidrosis, and 52% of them presented a great improvement. CONCLUSION:
      Treatment of facial hyperhidrosis with oxybutynin is a good alternative to
      sympathectomy, since it presents good results and improves quality of life, in
      addition to not exposing patients to the risk of experiencing the side effects of
      sympathectomy.

PMID- 21738961
TI  - Histopathological and epidemiological profile of cases of primary cutaneous
      melanoma diagnosed in Criciuma-SC between 2005 and 2007.
AB  - BACKGROUND: Melanoma is a skin tumor with the highest mortality, despite
      representing only 5% of the total. The incidence has increasing all over the
      world especially among fair-skinned individuals and the Criciuma, with a
      predominance of Italian ethnic,most susceptible to this type of tumor. OBJECTIVE:
      To know the epidemiological profile and histopathology of primary cutaneous
      melanoma in Criciuma,and compares them with literature. METHODS: We conducted a
      retrospective study, sectional and the pathological reports of melanoma primary
      in Criciuma, between January 2005 and December 2007. Were analyzed the population
      affected by sex and age, topography, histologic type, the Clark level and Breslow
      thickness. RESULTS: There were 72 reports. The age ranged from 15 to 85 years,
      with an average of 51 years. The most frequent localization in men was the trunk
      (60%) in women predominated in the lower limbs(30.5%). The most frequent
      histological type was the extensive superficial (50%). The Clark's level, the
      most frequent was level III(32.3%) followed by Level I (29.2%). Most melanomas
      Breslow had in situ(29.6%). CONCLUSION: The profile of patients with cutaneous
      melanoma in Criciuma-SC has characteristics similar to those described in the
      literature and world with regard to gender, age, topography and histology. The
      topography of the lesion, the study shows the importance of a clinical stricter
      mainly the trunk in men and women in the lower limbs. In this study there is a
      high incidence of melanoma per 100,000 in habitants, higher than the national
      average and state. On the other hand, melanomas showed a predominance of Breslow
      considered more favorable prognosis.

PMID- 21738962
TI  - Nosological profile in a dermatology referral center in the state of Amazonas 
      Brazil.
AB  - BACKGROUNDS: Fundaments: Skin diseases are associated wih high morbidity, low
      mortality and low rate of hospitalization. However, they can cause considerable
      interference in physical and emotional well-being of the individual. Several of
      them reach large population, requiring specific interventions for their control.
      OBJECTIVE: To describe the frequency of skin disease diagnosed in the dermatology
      service in Manaus, capital of Amazonas State. METHODS: We collected data on
      registered sex, age, origin and diagnostics for the first consultation of
      patients attended between January 2000 and December 2007. RESULTS: Of the 56.024
      recorded visits, we obtained 56.720 cases of dermatological diagnoses, being the
      most common sexually transmitted diseases (25,12%), allergic skin disesases
      (14,03%), unspecified dermatoses (13,01%), leprosy (6,34%) and acne, seborrhea
      and related diseases (5,05%). The frequency was similar for both sexes, aged 20
      29 years predominated and Manaus the origin most reported. CONCLUSIONS: The
      pattern of skin diseases identified in this study may serve as a baseline to
      managers of health system in the region develop strategies for prevention and
      control of dermatoses, with emphasis on sexually transmitted diseases, allergic
      skin diseases, leprosy and acne.

PMID- 21738963
TI  - Prevalence of dermatosis in scholars in the region of ABC paulista.
AB  - BACKGROUND: Literature shows that prevalence of skin diseases in children and
      adolescents aged 7-14 years is very significant, as well as lack of treatment
      worsening the situation. OBJECTIVES: An investigative analysis was conducted to
      determine the prevalence of skin diseases in individuals 714 years and focus on
      whether or not they are related directly to their respective socio-economic
      status. METHODS: 200 children and adolescents were examined aged 7-14
      years,between August and November 2006,100 children in two public schools located
      in the periphery and 100 in two private schools located in upper middleclass
      neighborhood in Santo Andre,located in Sao Paulo.Investigative method used was
      the clinical examination of the whole skin, mucous areas and palpable ganglia,and
      the population sample analyzed according to the chi-square. RESULTS: 87.5% of
      children had some skin disease.46 dermatoses were found,the most
      important:a)melanocytic nevi (p <0.001);b)acne grade II (p = 0.004);c)pityriasis
      alba (p <0.001);d)livedo reticularis (p = 0.025); e)pediculosis (p
      <0.001);f)asteatosis (p <0.001);g) frictional dermatitis (p = 0.007).Small
      prevalence of skin diseases was observed in children in public schools (53.14%).
      CONCLUSIONS: This population sample indicated that 87.5% of children had skin
      diseases,which prevalence was much higher than those found in the literature(30
      50%),showing a lightly enhanced prevalence in public schools.The study showed the
      neglect of parents and caregivers,indicating the need for interference from
      public policy,which lack certainly is responsible for high rate and can increase
      it.

PMID- 21738964
TI  - Prevalence of pediatric dermatoses in a university hospital in southeastern
      Brazil.
AB  - BACKGROUND: Numerous dermatoses affects children, depending on age, region and
      socioeconomic status. OBJECTIVE: To determine the prevalence of pediatric
      dermatoses at the Dermatology Department of a University Hospital, involving the
      diagnosis, age and sex. METHODS: Epidemiologic cross-sectional study carried out
      in the period between July 2006 and December 2007. There were reviewed the
      handbooks of 264 patients from the Pediatric Dermatology Department of a
      University Hospital in this period. The dependent variable was the existence or
      not of dermatoses in children of age up to 19 years. Independent variables were:
      clinical diagnosis, sex and age. RESULTS: Of the 264 handbooks reviewed, there
      was a higher prevalence of allergic dermatoses in 74 cases (28,0%), followed by
      inflammatory dermatoses in 49 cases (18,6%), pigmentary dermatoses in 42 cases
      (15,9%), infectious dermatoses with 38 cases (14,4%), benign tumors in 25 cases
      (9,5%), miscellaneous in 14 cases (5,3%), genodermatosis with 12 cases (4,5%) and
      skin annexes disorders with 10 cases (3,8%). The infants represented 11,3 % of
      the total, the pre-school 15,9 %, the schoolboys 48,8 %, and the adolescents 23,8
      %. There was greater prevalence of allergic dermatoses in pre-school with 15
      cases (35,7%), infants with 10 cases (33,3%) and schoolboys with 39 cases (30,2
      %). Among adolescents are highlighted inflammatory dermatoses. The study showed
      no statistical differences between sex and age. CONCLUSIONS: The study of the
      epidemiological profile makes easy the diagnosis of pediatric dermatoses
      encouraging good history and search for prevention.

PMID- 21738965
TI  - Adverse cutaneous reactions to epidermal growth factor receptor inhibitors: a
      study of 14 patients.
AB  - BACKGROUND: Cetuximab and erlotinib, epidermal growth factor receptor inhibitors,
      often cause peculiar adverse cutaneous reactions. OBJECTIVES: Our aim was to
      evaluate adverse cutaneous reactions and their management in patients undergoing
      treatment with cetuximab and erlotinib. PATIENTS AND METHODS: Between March/2005
      and September/2009, we observed 14 patients with a mean age of 59.6 years
      undergoing treatment with cetuximab (7) or erlotinib (7), due to lung(10) or
      colorectal cancer (4). We evaluated the interval between introduction of the drug
      and onset of symptoms, treatment response, and the clinical pattern of evolution
      of the cutaneous reaction retrospectively. RESULTS: Twelve patients presented
      papular-pustular eruption typically affecting the face, chest and back, which
      appeared in average 13.5 days after starting the drug treatment. The patients
      underwent oral treatment with minocycline or doxycycline and topical treatment
      with metronidazole, benzoyl peroxide and/or corticosteroids. All patients showed
      improvement of the lesions. Five patients presented periungual pyogenic
      granulomas, which were associated with paronychia in 4 cases, after an average of
      8 weeks of treatment. There was improvement of the lesions with topical treatment
      (antibiotics, corticosteroids and antiseptics). Xerosis was observed in some
      patients. Other less frequent adverse side effects such as telangiectasia and
      angiomas, hair and eyelash alterations, and eruptive melanocytic nevi were also
      described. Treatment with epidermal growth factor receptor inhibitor was
      maintained in most patients. CONCLUSION: The increasing use of these targeted
      therapies requires knowledge of their adverse cutaneous side effects to ensure
      timely intervention in order to allow the continuation of the therapy.

PMID- 21738966
TI  - Reproducibility of histopathologic diagnosis of skin diseases by digital
      photomicrographs versus conventional optical microscopy.
AB  - BACKGROUND: Telepathology is considered a good alternative for a second opinion
      consultation. Its implementation is desirable, but studies to confirm its
      practical application are required. OBJECTIVES: To evaluate the reproducibility
      of histopathologic diagnoses of skin diseases obtained through digital
      photomicrographs compared with conventional microscopy. METHODS: We evaluated the
      surgical specimens of 135 patients using an optical microscope. After 4 weeks,
      the same consultants independently evaluated a total of 1,738 digital
      photomicrographs obtained from the histopathological slides. We estimated the
      overall rate of intra and interobserver agreement, and the Kappa coefficient was
      obtained with the categorization of the skin diseases: neoplastic skin diseases,
      infectious-contagious skin diseases and non-infectious-contagious skin diseases.
      RESULTS: Consultant 1 obtained an agreement of 88.1% (95% CI = 81.5% - 93.1%)
      between conventional microscopy and images. Consultant 2 obtained an agreement of
      80.7% (95% CI = 73.1% - 87%). The interobserver agreement for the microscopy
      analysis was 81.5% (95% CI = 73.9% - 87.6%). The same analysis using
      microphotography showed an agreement of 85.9% (95% CI = 78.9% - 91.3%). The Kappa
      coefficient, which evaluated the categorized skin diseases, was 98.6% for
      Consultant 1, 93.1% for Consultant 2, 95.8% for interconsultant analyses of
      images and 95.9% for interconsultant analyses using conventional optical
      microscopy. All of these values are considered optimal. CONCLUSION: The
      evaluation of microphotographs shows a good level of reproducibility when
      compared to traditional microscopy and, therefore, is a viable option for a
      second opinion consultation in dermatopathology.

PMID- 21738967
TI  - Advances in the treatment of cutaneous leishmaniasis in the new world in the last
      ten years: a systematic literature review.
AB  - INTRODUCTION: The therapeutic arsenal against cutaneous leishmaniasis is very
      limited. Pentavalent antimonial compounds have been the drugs of choice for
      treatment of this disease for over 50 years. Despite their effectiveness, these
      drugs require daily injections, have many side effects and present prolonged
      healing time. OBJECTIVE: To carry out a systematic literature review on the
      advances in the treatment of cutaneous leishmaniasis in the new world in the last
      ten years. METHODS: We conducted an electronic search on the Pubmed and LILACS
      database as well as on the SciELO electronic library in June 2009. The search
      words in English were: "cutaneous", "leishmaniasis" and "treatment". We included
      only randomized, double-blind and placebo controlled trials. We used the Jadad
      scale to assess the quality of the selected studies. RESULTS: According to the
      inclusion and exclusion criteria, only eight articles were selected. The drugs
      evaluated in the selected studies were glucantimeA(r), miltefosine,
      immunotherapy, imiquimod, rhGM-CSF and pentoxifylline, and paromomycin.
      CONCLUSION: Although cutaneous leishmaniasis is a major public health issue, the
      published data on the use of new drugs for the treatment of cutaneous
      leishmaniasis in Brazil are still quite limited.

PMID- 21738968
TI  - Sun protection factor: meaning and controversies.
AB  - The Sun Protection Factor (SPF) is the most important data to quantify the
      effectiveness of a sunscreen, being universally accepted. The method is based on
      determining the minimum erythematous dose (MED), defined as the smallest amount
      of energy required for triggering the erythema, in areas of protected and
      unprotected skin. The SPF value is then calculated as the ratio between the MED
      of protected and unprotected skin. The first publication of a method for
      determining the SPF was presented in 1978 by the U.S. FDA agency, followed by
      other publications of FDA and other international regulatory agencies. Although
      considered the reference method for quantification of sunscreen efficacy of
      topical products, there are controversies in literature about the method for
      determining the SPF and the implications of the real conditions of use in the
      protection achieved in practice by users.

PMID- 21738969
TI  - Immunology of paracoccidioidomycosis.
AB  - Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America,
      among immunecompetent patients. It's caused by the dimorphic fungus
      Paracoccidioiddes brasiliensis. Investigations regarding its immunopathogenesis
      are very important in the understanding of aspects related to natural history, as
      the protective immunity, and the relationship between host and parasite; also
      favoring the knowledge about clinical patterns and the elaboration of therapeutic
      strategies. The disease clinical polymorphism depends, at least, of the immune
      response profile according to the tissue and blood released citokynes, resulting
      in tissue damage.

PMID- 21738970
TI  - Child abuse: skin markers and differential diagnosis.
AB  - Reports of child abuse have increased significantly. The matter makes most
      physicians uncomfortable for two reasons: a) Little guidance or no training in
      recognizing the problem; b - Not understanding its true dimension. The most
      common form of child violence is physical abuse. The skin is the largest and
      frequently the most traumatized organ. Bruises and burns are the most visible
      signs. Physicians (pediatricians, general practitioners and dermatologists) are
      the first professionals to observe and recognize the signs of intentional injury.
      Dermatologists particularly, can help distinguish intentional injury from
      accidental, or from skin diseases that mimic maltreatment.

PMID- 21738971
TI  - Rare cutaneous metastasis from a probable basaloid carcinoma of the colon
      mimicking pyogenic granuloma.
AB  - Acrometastasis is a rare occurrence, especially when affecting the hands. It
      represents around 0.007-0.2% of all metastatic lesions. The most common site of
      origin is the lung, accounting for 40-50% of all cases reported in the
      literature. Kidneys and breasts are other sites also associated with neoplastic
      lesions that disseminate to the hands. More rarely, the site of origin may be the
      gastrointestinal tract or other systemic tumors or sarcomas. Early diagnosis is
      difficult, since the condition may be asymptomatic or may mimic tenosynovitis,
      arthritis, paronychia, pyogenic granuloma or a local infection. In the present
      paper, the authors report on a patient with the diagnosis of acrometastasis on
      both hands originating from a basaloid carcinoma of the anal canal. Response to
      radiotherapy was poor.

PMID- 21738972
TI  - Cutaneous tuberculosis and squamous-cell carcinoma.
AB  - The incidence of all forms of cutaneous tuberculosis, including lupus vulgaris
      (the most common form) decreased progressively in developed countries during the
      twentieth century, this change being attributed to improved living standards and
      specific therapy. Despite the decrease in cutaneous tuberculosis, some cases are
      still found and correct diagnosis and management are fundamental, both for the
      patients and for public health. Long lasting, misdiagnosed or untreated cutaneous
      tuberculosis may lead to different forms of cancer. This case report involves a
      74-year old male farmer with lupus vulgaris on his face. During anti-tuberculosis
      treatment he developed a tumor on his forehead, which was histologically
      confirmed as a squamous cell carcinoma.

PMID- 21738973
TI  - Periorbital hemangiomas: the need for active management - report of two cases.
AB  - Hemangioma is the most common tumor of childhood and is commonly located on the
      head or neck. The orbit is often affected and early and aggressive intervention
      is required to prevent serious visual complications. This paper reports on two
      cases. In the first case, the patient's vision was impaired, while in the second
      case a deep hemangioma affecting adjacent areas was confirmed radiologically.
      Treatment with aggressive systemic corticotherapy was successful, thus avoiding
      permanent damage to the patients' vision. Furthermore, esthetic outcome was
      satisfactory. The treatment of choice is oral corticosteroids and management
      should be individualized and should include careful follow-up to monitor possible
      adverse effects.

PMID- 21738974
TI  - Primary cutaneous large B-cell lymphoma of atypical presentation: case report.
AB  - Primary cutaneous lymphomas are defined as lymphocytic neoplasias that present
      themselves clinically in the skin without extracutaneous disease at diagnosis and
      up to 6 months after it. The authors report the case of an elderly male patient,
      with a three- month-history of papules in the axilla which evolved into painful
      ulceration. Examination found deep ulcer with irregular borders ,infiltrates, in
      the right axilla. Physical and additional examinations did not evidence disease
      at distance. Histopathology revealed dense and diffuse dermic sample infiltrate
      of atypical lymphocytes. Imunohistochemistry shows expression of CD20 and bcl-2
      antigens , with negative CD10, configuring diagnosis of cutaneous large B-cell
      lymphoma. In this type of cutaneous lymphoma, primary cutaneous manifestation is
      rare ,the incidence in men is lower and it is most commonly located in the lower
      limbs.

PMID- 21738975
TI  - Linear chronic discoid lupus erythematosus following the lines of Blaschko.
AB  - Linear chronic discoid lupus erythematosus is a rare manifestation of cutaneous
      lupus in which erythematous, atrophic, dyschromic lesions are located along the
      lines of Blaschko. This report describes the case of a 15-year old boy with a 2
      year history of discoid, erythematous, hyper and hypopigmented lesions with
      central atrophy, situated along the lines of Blaschko on his right arm.
      Histopathology showed epidermal atrophy, hyperkeratosis, follicular plugging,
      thickening of the basement membrane zone, and superficial and deep chronic
      perivascular and periadnexal inflammatory infiltrate, with dermal mucin deposit,
      thus confirming diagnosis. A total of 14 cases have been described of this
      variant, the onset of which is often in childhood. There is no difference in
      incidence between genders. Lesions most commonly develop on the face. There have
      been no reports of any association with systemic disease.

PMID- 21738976
TI  - Macrodactyly with skin hypertrophy: a minimal form of the Proteus syndrome.
AB  - The Proteus syndrome was described 1983 . It has asymmetric gigantism of the
      limbs, verrucous epidermal naevi, cerebriform enlargement of the plantar region,
      vascular malformations and neoplasms, as lipomas. It received this denomination
      after Proteus from the Greek mythology, who had the ability to change his form .
      A 15 year-old boy, reported a congenital hypertrophy with syndactily of the
      second and third right fingers . The second case is a 35 year-old man, who
      reported that since birth the second right toe was bigger than the other toes,
      skin hypertrophy was also observed. These cases document a localized form if the
      Proteus syndrome, which may widen the spectrum of its variability.

PMID- 21738977
TI  - Mycosis fungoides: case report treated with radiotherapy.
AB  - Mycosis fungoides is a rare type of non-Hodgkin's lymphoma of T cells that
      primarily affects the skin. It is characterized by the presence of erythematous
      plaques that evolve into ulcerated lesions, tumors throughout the skin or even
      bone marrow infiltration in advanced stages. Chemotherapy and topical steroids,
      phototherapy and radiotherapy are treatment options for early cases. This study
      reports the case of patient with multiple tumor lesions in the skin already
      biopsied with diagnosis of mycosis fungoides. The patient was refractory to both
      treatments with topical chemotherapy and phototherapy. It was then indicated
      total skin irradiation with electrons.

PMID- 21738978
TI  - Mucous membrane pemphigoid with severe esophageal stricture.
AB  - Mucous membrane pemphigoid (MMP) is a rare nosological entity. MMP consists of a
      clinical phenotype in which several autoimmune subepidermal bullous diseases are
      classified. It occurs predominantly in the mucous membranes and usually results
      in scarring. Esophageal involvement in MMP is rare and is generally seen in
      patients in whom lesions are widespread. The most common alterations are multiple
      esophageal membranes or strictures. In the present case, the authors report on a
      patient with MMP without any skin lesions and with severe esophageal strictures
      who went into remission following use of intravenous immunoglobulin.

PMID- 21738979
TI  - Solitary subungual neurofibroma: a previously unreported finding in a male
      patient.
AB  - A neurofibroma is a hamartomatous proliferation of neuromesenchymal origin. It
      may be found in combination with neurofibromatosis or in the form of a solitary
      tumor. Clinical presentation as a solitary subungual tumor is very rare.
      Neurofibroma is more common in females and surgery is the treatment of choice.
      The present paper reports the case of a male patient with a subungual tumor on
      his toe. Biopsy and immunohistochemistry findings were compatible with a
      neurofibroma. To date, fewer than ten cases of subungual neurofibromas
      unassociated with von Recklinghausen's disease have been documented, this being
      the first case to be reported in Brazil and the only report worldwide to have
      described this condition in a male patient.

PMID- 21738980
TI  - Florid cutaneous papillomatosis and acanthosis nigricans maligna revealing
      gastric adenocarcinoma.
AB  - This paper reports the case of a 57-year-old, previously healthy male with no
      systemic symptoms who over a short period of time developed multiple wart-like
      lesions on his trunk, limbs and face, typical lesions of acanthosis nigricans in
      the major body folds and tripe palms. Diagnostic tests revealed a metastatic
      gastric adenocarcinoma. Despite the implementation of therapy, which had a
      transient effect on the tumor and skin lesions, the patient died in 14 months.
      The association of these three paraneoplastic dermatoses (florid cutaneous
      papillomatosis, acanthosis nigricans maligna and tripe palms) in the same
      patient, apparently with a common pathogenic mechanism, is noteworthy.

PMID- 21738981
TI  - Acute respiratory distress syndrome as a complication of generalized pustular
      psoriasis.
AB  - Since 1991, eight cases of pulmonary leak capilary syndrome have been described
      associated with pustular or erythrodermic psoriasis induced or not by the use of
      acitretin or sirolimus - being one of the cases, fatal. We report the case of a
      female patient with diagnosed GPP or von Zumbusch and multiple hospitalizations
      due to such condition. At that time, the condition was evolving with pulmonary
      onset and resolution with corticosteroids. The patient was not using any
      previously described medication that could precipitate pulmonary condition
      (methotrexate and acitretin). This is a rare complication associated with
      psoriasis which has not been described in Brazilian patients so far.

PMID- 21738982
TI  - Pachydermoperiostosis: the complete form of the syndrome.
AB  - Pachydermoperiostosis is a rare genodermatosis with various clinical
      presentations that include pachydermia (thickening of the skin), finger clubbing
      and periostitis. Its pathogenesis is uncertain and the condition affects mainly
      men. This report describes the case of a patient with typical, exuberant skin
      manifestations and classic radiological findings of this syndrome in its complete
      form.

PMID- 21738983
TI  - Granuloma inguinale (Donovanosis).
AB  - The authors present images of two of the most common clinical forms of granuloma
      inguinale (donovanosis) in males and females. Donovanosis is considered a
      sexually transmitted disease that is endemic in tropical and subtropical regions
      of the world. Two microscopic images are also shown, one of a direct smear (the
      presence of Donovan bodies within large mononuclear cells identified using Giemsa
      stain) and the other of typical histological findings (rod-shaped Donovan bodies
      within a mononuclear histiocyte).

PMID- 21738984
TI  - Paracoccidioidomycosis in a patient with cervical cancer.
AB  - This report describes the case of a female patient with paracoccidioidomycosis
      associated with a stage IIIB cervical carcinoma. Paracoccidioidomycosis in
      association with a malignant tumor occurs in 0.16% to 14.1% of cases in
      accordance with different case series. In cases in which the cancer is
      disseminated, the fungal infection may behave opportunistically.

PMID- 21738985
TI  - Multiple basal cell carcinomas in the pubic area in a patient with skin type IV:
      case report.
AB  - Basal cell carcinoma is the most common type of malignant cutaneous neoplasm in
      humans, being more frequently located in exposed areas and in fair-skinned
      individuals. It is reported the case of a 62-yearold female patient, brown
      skinned ,with multiple lesions with edges slightly raised, reddish-brown in the
      pubic region, whose clinical diagnosis was pigmented basal cell carcinoma,
      confirmed by histopathology. Immunohistochemistry of the lesions was negative for
      the detection of papilloma virus.

PMID- 21738986
TI  - Systemic capillary leak syndrome.
AB  - The systemic capillary leak syndrome is rare and caused by increased capillary
      permeability. Several etiologies are involved. In our Department of Dermatology
      the main one is unstable psoriasis. Several treatments are used and many are
      still under study. Our objective was to present this potentially fatal medical
      condition that occurs in our specialty.

PMID- 21738987
TI  - Leg ulcers and anticardiolipin antibodies.
AB  - Prothrombotic phenomena are described in leg ulcers of different etiologies. This
      work attempts to verify the prevalence of anticardiolipin antibodies in such
      patients. For this purpose, 151 patients with leg ulcers and 150 control patients
      were studied and it was obtained clinical data and anticardiolipin antibodies
      titers. Anticardiolipin antibodies were detected in 7,2 % of the patients from
      the ulcer group against 1.3% of the patients in the control group (p=0.01).
      However, clinical characteristics were not different in patients with and without
      anticardiopilin antibodies.

PMID- 21738988
TI  - The use of high frequency waves to treat onychomycosis: preliminary communication
      of three cases.
AB  - The research evaluated the efficacy of high frequency waves in the treatment of
      onychomycosis in three patients during twelve months through the clinical
      examination of nails and also through mycological examination. The causative
      agent of the mycosis, in the three patients, was the dermatophyte Trichophyton
      rubrum and after application of high frequency, it was possible to notice a great
      improvement in the appearance of nails and also growth inhibition in culture
      despite the fact that the mycological examination remained positive. The
      preliminary study of the three cases demonstrated that the fungistatic activity
      of high frequency waves is a promising method to be used in combination with
      conventional drugs.

PMID- 21738989
TI  - Case for diagnosis.
AB  - Hidradenitis suppurativa is a chronic inflammation of the apocrine glands. It
      usually starts at or soon after puberty, and women are more often affected than
      men. The most affected sites are the axillae; however, other regions rich in
      apocrine glands may also be affected. Involvement restricted to the inframammary
      fold alone is rare and to the best of our knowledge there have been no reports of
      any similar cases. The etiology of this condition has yet to be fully clarified.

PMID- 21738990
TI  - Case for diagnosis.
AB  - Marjolin's ulcer is a term used to describe a malignant transformation that
      originates in chronic skin lesions. These neoplasms may be more aggressive than
      those unassociated with healing processes and are frequently overlooked or
      inadequately treated. This case report describes the occurrence of a squamous
      cell carcinoma occurring at the site of a burn scar and emphasizes the need for
      early diagnosis and treatment in order to assure better prognosis.

PMID- 21738991
TI  - Do you know this syndrome?
AB  - Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK)
      syndrome is a rare autosomal recessive skin disorder characterized by the
      association of diffuse, transgressive palmoplantar keratoderma with
      sclerodactyly, linear hyperkeratotic plaques generally located in flexures, and
      congenital ichthyosis. The patient is physically and mentally healthy and has no
      history of any problems related to teeth, nails, hair or mucous membranes.
      Treatment is based on the use of topical keratolytics and oral retinoids.

PMID- 21738992
TI  - Do you know this syndrome?
AB  - Bloch-Sulzberger syndrome (incontinentia pigmenti) is a rare genodermatosis that
      affects predominantly females, since it is generally lethal to male fetuses in
      utero. It is characterized principally by skin lesions, but may also involve
      dental, ophthalmological and neurological abnormalities. The skin lesions are
      present in four different phases: vesicular, verrucous, hyperpigmented and
      atrophic/hypopigmented. Their sequence is irregular and overlapping of stages is
      common.

PMID- 21738993
TI  - Comparative dermatology: skin lesion produced by attack of jellyfishes (Physalia
      physalis).
AB  - It is reported the case of a 21-year-old female bather with a skin lesion, heart
      shaped ,characteristic of attack by jellyfish.

PMID- 21738994
TI  - SBD-RESP in active search for leprosy cases.
AB  - BACKGROUND: The Brazilian Society of Dermatology of the State of Sao Paulo (SBD
      RESP), supported by the Sao Paulo State Foundation Against Leprosy and acting
      jointly with Sao Paulo State Services of Dermatology, accredited by the Brazilian
      Society of Dermatology, launched the campaign "SBD-RESP in active search for
      leprosy cases". OBJECTIVES: To assist the National Leprosy Control Program in
      eliminating Hansen's disease. METHODS: All of the Sao Paulo State Services of
      Dermatology, accredited by the Brazilian Society of Dermatology, were invited to
      join the campaign. The 17 Services which accepted to participate received a
      spreadsheet of data and models of informative materials about the disease. The
      campaign lasted from May to July 2010. At the end of the campaign, each Service
      sent the spreadsheet data for statistical analysis. RESULTS: 1,718 people were
      examined and 90 cases of Hansen's disease were diagnosed. Most of the individuals
      infected were male and white and presented similar percentages of multibacillary
      and paucibacillary groups. Twelve percent had a family history of leprosy. The
      highest number of cases was detected in Sao Paulo city, followed by the region of
      Presidente Prudente, located in the countryside of Sao Paulo State. The detection
      rate in children younger than 15 years old was 4%. CONCLUSION: The campaign
      results show the importance of the SBD-RESP initiative. It is suggested that
      similar actions be repeated and extended to other regional offices of the
      Brazilian Society of Dermatology.

PMID- 21738998
TI  - OSAS in children: where are we?

PMID- 21738999
TI  - Effect of green propolis on oral epithelial dysplasia in rats.
AB  - Studies have demonstrated that flavonoid compounds of green propolis have
      antitumoral activity. STUDY DESIGN: Experimental study. AIMS: To evaluate the
      effect of a hydroalcoholic extract of green propolis (EPV) on chemically induced
      epithelial dysplasias in rat tongues. METHODS AND MATERIALS: DMBA was brushed on
      the lingual dorsum of rats 3x/week on alternate days--100 (PROP1), 200 (PROP2)
      and 300 mg/kg (PROP3) EPV was administered orally for 20 weeks. EPV or DMBA were
      replaced by their vehicles and applied as positive (TUM1 and TUM2) and negative
      controls (CTR1 and CTR2), respectively. The lingual epithelium was histologically
      analyzed and graded according a binary system and the WHO classification; the
      data were compared using ANOVA (*p<0.05). RESULTS: The EPV yield was 41% and the
      flavonoid yield was 0.95+/-0.44%. According to the Binary System, TUM1, TUM2 and
      PROP1 were considered high risk lesions, with significantly higher morphological
      alteration rates compared to the other groups (p<0.05), which were considered low
      risk lesions. Based on the WHO classification, moderate dysplasia was TUM1 and
      TUM2, mild dysplasia was PROP1, PROP2 and PROP3, and non-dysplastic epithelium
      was CTR1 and CTR2. CONCLUSION: EPV seems to play an important protective role
      against chemically-induced lingual carcinogenesis in rats.

PMID- 21739000
TI  - Histology of sheep temporal bone.
AB  - Previous studies suggest that there is an excellent correlation between the
      morphology and dimensions of ear structures in sheep and human beings. AIM: To
      analyze and describe the histology of structures inside the temporal bone in
      sheep. MATERIAL AND METHODS: A total of 307 slides obtained from vertical and
      horizontal sections of the temporal bone of eight sheep were analyzed. Structures
      were classified as similar or not similar to human structures, based on
      cellularity and histological architecture parameters. STUDY DESIGN: Experimental.
      RESULTS: The study revealed similarities between sheep and humans in terms of
      type of epithelium, bone component, spaces in the auditory meatus, in addition to
      a marked histological resemblance of cellularity and that of the structures
      surrounding the ear. The main differences observed were the presence of an
      anatomic bulla, the absence of aeration in the mastoid and the inferior opening
      of the hypotympanum into the bulla in sheep. CONCLUSION: Based on these
      observations, it is possible to conclude that sheep represent an adequate option
      for training and research in otologic surgery.

PMID- 21739001
TI  - Incidence of tinnitus in mp3 player users.
AB  - Exposure to loud noise is one of the main causes of tinnitus. AIM: To analyze the
      incidence of tinnitus in mp3 player users and non-users. MATERIAL AND METHOD: One
      hundred subjects aged from 15 to 30 years were enrolled, 54 of them were regular
      mp3 player users and 46 were not. Patients with continuous tinnitus for at least
      6 months completed the Tinnitus Handicap Inventory (THI) and were tested with
      high frequency audiometry and transient-evoked otoacoustic emissions (TAOE).
      STUDY DESIGN: A cross-sectional cohort study. RESULTS: The incidence of tinnitus
      in non-users was about 8 %; in mp3 player users it was about 28 %, a
      statistically significant difference. Hearing thresholds at 8 kHz were
      significantly higher in tinnitus patients that used mp3 portable players.TAOE
      were reduced at 2 kHz in the users group. No statistically significant difference
      was found in the THI scores between the two groups. CONCLUSION: Tinnitus was more
      frequent in teenagers and young adults who regularly listen to mp3 music in
      players. Moreover, the incidence of tinnitus among mp3 player users was
      associated with higher hearing thresholds at 8 kHz and lower TOAE at 2 kHz.

PMID- 21739002
TI  - Radiotherapy for early glottic cancer and salvage surgery after recurrence.
AB  - Early glottic cancer can be effectively treated with radiation or surgery, but
      recurrence is a possibility when using any of the treatment modalities. AIM: To
      assess the outcome of radiotherapy as initial treatment in the control of
      squamous cell carcinoma of vocal cord (T1) and the effectiveness of salvage
      surgery (endoscopic or open) after treatment failure. MATERIALS AND METHODS: A
      retrospective study was based on the analysis of medical records from 43 patients
      with T1 squamous cell carcinoma of the glottis, radiotherapy as initial treatment
      and follow-up period of five years. RESULTS: The rate of recurrence after
      radiotherapy was 30.2% of the cases, mean diagnosis interval was 29.5 months. As
      an option for salvage treatment, patients underwent open partial laryngectomy or
      endoscopic surgery with control rates of 77.7% and 25% respectively. CONCLUSION:
      Our cases showed high rates of recurrence after radiotherapy and open partial
      laryngectomy was more effective for the salvage surgery.

PMID- 21739003
TI  - 3D didactic model and useful guide of the semicircular conducts.
AB  - Knowledge of the anatomy and physiology of the semicircular canals and their
      central pathways is essential for the diagnosis of vestibular pathology. This 3
      dimensional (3D) scheme of the Semicircular Canals (SSCC) is a teaching tool and
      a useful reference guide for rapid consultation. MATERIAL AND METHODS: A
      multicolored cardboard model is accompanied by a user manual which provides a
      thorough description of the tool for the most common vestibular diseases.
      RESULTS: Although results cannot be quantitatively assessed, the model has been
      well received at several Latin American scientific conferences. The model is
      often understood with verbal instruction only; nevertheless, a printed user
      manual is included. CONCLUSIONS: This 3 dimensional (3D) model of the
      Semicircular Canals (SSCC) is a practical, low cost tool for use in private and
      academic settings.

PMID- 21739004
TI  - Mucosa-associated lymphoid tissue in individuals with AIDS.
AB  - Vestibular folds (VF) protect upper airways, but contain fewer immune cells in
      AIDS patients, which affects the structure of lymphoid follicles (LF). OBJECTIVE:
      To characterize fibrosis and immunoglobulin production in vestibular fold
      lymphoid tissues of AIDS patients with or with no infection and malnutrition.
      MATERIALS AND METHODS: A retrospective study of 71 adult vestibular fold autopsy
      specimens. The morphological analysis was done using the picrosirius staining
      method. Immunohistochemical methods consisted of anti-IgA, anti IgG, and anti IgM
      antibodies. RESULTS: Fibrosis was less intense in AIDS patients compared to
      subjects without AIDS; the same applied to patients with infection or
      malnutrition. IgA and IgG titers were higher in AIDS patients; IgM titers were
      higher in cases with infection. CONCLUSION: This study helps understand
      variations in lymphoid follicle components of AIDS patients; it also shows the
      influence of architectural changes and the effect of associated respiratory
      infection and malnutrition on lymphoid follicle function.

PMID- 21739005
TI  - Hydroxyapatite granules used in the obliteration of mastoid cavities in rats.
AB  - Prospective experimental study in which we created a bony defect in the mastoids
      of rats and filled it up with hydroxyapatite to evaluate bone regeneration, to
      solve the problems of open cavities after mastoidectomies that frequently present
      with otorrhea, infection, granulation tissue and hearing loss. OBJECTIVE: The aim
      was to evaluate bone regeneration in defects created in the mastoids of rats,
      using hydroxyapatite, to see how much of the cavity we could reduce. MATERIAL AND
      METHODS: Twelve rats Wistar-Furth were used. A 0.5 x 0.5 cm bone defect was
      created in both temporal bones of the rats, and filled with 15 micrograms of
      hydroxyapatite. The left side was used as control. The animals were slaughtered
      40 days afterwards and histology analyses were carried out. RESULTS: In the
      hydroxyapatite group, the new bone growth involved an area of 68.53% of the
      total; and in the control group it was only of 15.97%. DISCUSSION AND CONCLUSION:
      It was observed a very good hydroxyapatite integration to the temporal bone in
      this experimental model. The microscopic results were superior with the use of
      hydroxyapatite when compared to the control group. It is a safe method and easy
      to apply to solve the problems of open cavities with chronic discharge and
      difficult to clean.

PMID- 21739006
TI  - Complications in blepharoplasty: how to avoid and manage them.
AB  - Complications in blepharoplasty are uncommon and, when they occur, they are
      usually mild and transient, such as hematomas and chemosis. However, sometimes
      they can be severe, such as blindness, or they might require surgical correction,
      such as ectropion. OBJECTIVE: To evaluate the results and complications of
      transcutaneous blepharoplasty performed in the same procedure, discussing how to
      treat and how to avoid them. METHODS: A retrospective study of 200 medical
      records of consecutive patients that underwent transcutaneous blepharoplasty from
      January 2007 to January 2009. The variables analyzed were age, gender,
      complications, clinical outcome, patient satisfaction, and photographic
      documentation. RESULTS: The incidence of complications was 9.5% (19 patients).
      The complications were 1 hematoma, 12 cases of chemosis and 13 patients who
      underwent canthoplasty, 6 patients with malposition of the lower eyelid (5
      retractions and 1 ectropion). Medical treatment was performed in 12 patients and
      revision surgery in 7 cases of all the patients who had complications.
      CONCLUSIONS: We demonstrated that blepharoplasty is a procedure with a high
      satisfaction and a low complication rate, and it is an excellent surgical
      procedure, when properly indicated.

PMID- 21739007
TI  - Prevalence of broncopulmonary and otorhinolaryngologic symptoms in children under
      investigation for gastroesophageal reflux disease: retrospective analysis.
AB  - Gastroesophageal reflux disease (GERD) is a common ailment in children, adding up
      to the evidence that gastroesophageal reflux is an important cofactor in upper
      airway disorders, especially in the pediatric population. It is very common for
      it to impact the upper and lower airways. Our goal was to assess the presence of
      otorhinolaryngological symptoms in children aged between one and twelve years in
      whom gastroesophageal reflux is suspected. MATERIALS AND METHODS: We assessed
      data from the charts of patients up to 12 years of age submitted to 24 hour pH
      measuring of one of two channels, placed at 2 and 5 cm from the LEE in order to
      confirm the diagnosis of Gastroesophageal Reflux Disease. RESULTS: We studied 143
      charts from children who underwent 24 hour pH measuring to investigate GERD;
      however, only 65 were included. The most prevalent symptoms in the children were
      bronchopulmonary, found in 89.2%, of sinonasal symptoms (72.3%), otologic (46.1%)
      and repetition UAW infections (44.6%). When we compared the presence of each
      group of symptoms of the results from the pH measuring, no significant
      differences were found between the symptoms and the pH measuring results.
      CONCLUSION: GERD can manifest in different ways and otorhinolaryngological
      symptoms are frequent in children.

PMID- 21739008
TI  - Aesthetic comparison of the ideal nasal radix height in Brazilians.
AB  - The harmony of the facial profile is widely influenced by the height and form of
      the nasal dorsum. A few millimeters can make the lateral view aesthetically more
      or less pleasing and adequate in a subject's face. Professionals working with
      facial aesthetics should focus not only on the surgical techniques for proposed
      outcomes, but also with the subtleties and subjectivity that characterize
      aesthetic concepts and judgment. MATERIAL AND METHODS: A prospective survey to
      evaluate the preferences of a group of healthcare professionals working with
      facial aesthetics, a group of fine artists, and lay people about the best nasal
      radix height; the survey involved comparing 3 different nasal radix heights using
      computer-altered photographs of women with measurements close to the Caucasian
      standard. RESULTS AND CONCLUSION: The lowest position of the nasal radix--close
      to the height of the pupil--was preferred (53%), followed by the middle position
      (superior crease of the eye). The highest position, resembling classic Greek
      statues, was considered the worst. The authors evaluated the effect of age,
      gender, and educational level on the choice of the best and worst female
      profiles.

PMID- 21739009
TI  - Epidemiology of middle ear and mastoid cholesteatomas: study of 1146 cases.
AB  - Middle ear cholesteatoma is an important and relatively common disorder which may
      have serious consequences. AIM: The purpose was to conduct a retrospective study
      of the statistics of 1,146 middle ear surgical procedures for middle ear
      cholesteatoma in adults and children of low income living in distant areas from
      our city. METHODS: From 1962 to 1988 there were 1,146 surgeries for unilateral or
      bilateral cholesteatomas in children and adults, which were reviewed for the
      following criteria: total number of surgeries, sex, onset of the first symptoms,
      duration of the disease, the site of perforation, the cholesteatoma site, changes
      in the ossicular chain, the contralateral ear, bilateral cholesteatomas, the site
      of residual cholesteatoma, and complications. RESULTS: Results are shown
      graphically on a pie chart. CONCLUSION: The etiology of cholesteatomas remains
      unknown. Epidemiological and statistical data, surgical reports, and conclusions
      of experimental studies are welcome, as they may provide support for clarifying
      the pathogenesis of cholesteatoma. Our results were compared with internationally
      published papers. We found no published papers on the epidemiology of
      cholesteatoma in the Brazilian literature.

PMID- 21739010
TI  - Polymorphisms in the 5-HTR2A gene related to obstructive sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is one of the most complex disorders of
      sleep; it involves several genetic factors that contribute to the phenotype.
      Serotonin (5-HT) regulates a variety of visceral and physiological functions,
      including sleep. Gene 5-HTR2A polymorphisms may change the transcription of
      several receptors in the serotoninergic system, thereby contributing to OSAS.
      AIM: To investigate the prevalence of T102C and -1438G/A polymorphisms in the 5
      HTR2A gene of patients with and without OSAS. MATERIAL AND METHOD: A molecular
      study of 100 index-cases and 100 controls of both genders. DNA was extracted from
      blood leukocytes samples and the regions that enclose both polymorphisms were
      amplified with PCR-RFLP. STUDY DESIGN: A cross-sectional case study. RESULTS:
      There was a significant prevalence of males in index cases compared to controls
      (p<0.0001). No significant genotypic differences between cases and controls were
      found in T102C polymorphisms (p=1.000).There were significant differences between
      the AA genotype of -1438G/A polymorphisms and patients with OSAS (OR:2.3;
      CI95%:1.20-4.38, p=0.01). CONCLUSION: Serotonergic mechanisms may be related to
      OSAS. There were no differences in the prevalence of T102C polymorphisms in
      patients with OSAS and the control group. There is evidence of an association
      between the -1438G /A polymorphism and OSAS.

PMID- 21739011
TI  - Vestibular rehabilitation with biofeedback in patients with central imbalance.
AB  - Central Nervous System disorders may cause important functional unbalance in the
      maintenance of balance and posture. There is no effective rehabilitation for
      these symptoms until now. OBJECTIVE: The aim of this paper is to evaluate the use
      of tongue electrotactile stimulation on patients with central imbalance using
      BrainPort. MATERIALS AND METHODS: This is a prospective case series study. We
      evaluated 8 patients with central imbalance, 6 men and 2 women, with mean age of
      67.75 years. The patients were submitted to Computed Dynamic Posturography (CDP)
      and then received 18 sessions of electrotactile stimulation by BrainPort(r)
      device for 20 minutes, twice a day. Then they were submitted to a new CDP test
      and to a self-perception scale to assess symptom remission, partial improvement
      and no improvement at all. RESULTS: 75% of the patients reported being more
      stable. There was no improvement in the balance control of the mass center in
      these patients. CONCLUSION: The patients were able to use the electrotactile
      stimulus to improve their balance control.

PMID- 21739012
TI  - Auditory processing in dysphonic children.
AB  - Contemporary cross-sectional cohort study. There is evidence of the auditory
      perception influence on the development of oral and written language, as well as
      on the self-perception of vocal conditions. The auditory system maturation can
      impact on this process. OBJECTIVE: To characterize the auditory skills of
      temporal ordering and localization in dysphonic children. MATERIALS AND METHODS:
      We assessed 42 children (4 to 8 years). STUDY GROUP: 31 dysphonic children;
      Comparison group: 11 children without vocal change complaints. They all had
      normal auditory thresholds and also normal cochleo-eyelid reflexes. They were
      submitted to a Simplified assessment of the auditory process (Pereira, 1993). In
      order to compare the groups, we used the Mann-Whitney and Kruskal-Wallis
      statistical tests. Level of significance: 0.05 (5%). RESULTS: Upon simplified
      assessment, 100% of the Control Group and 61.29% of the Study Group had normal
      results. The groups were similar in the localization and verbal sequential memory
      tests. The nonverbal sequential memory showed worse results on dysphonic
      children. In this group, the performance was worse among the four to six years.
      CONCLUSION: The dysphonic children showed changes on the localization or temporal
      ordering skills, the skill of non-verbal temporal ordering differentiated the
      dysphonic group. In this group, the Sound Location improved with age.

PMID- 21739013
TI  - DATASUS as a instrument for developing otologic public health policies.
AB  - Ear diseases are illnesses which represent a relevant group of morbidity. Otitis
      media, for instance, still is a public health problem today. OBJECTIVE: To
      correlate hospital morbidity of ear diseases according to data from the
      Information Technology Department of the Public Health Care System -SUS
      (DATASUS), through the Hospital Information System (SIH) with the Human
      Development Index (IDH) from each unit of the federation. To assess the use of
      this official data in the creation of otologic public health care policies.
      MATERIALS AND METHODS: Brazilian states were classified according to their
      respective IDH values. The percentage population from each state was calculated
      in relation to the entire population of the country, as well as the percentage of
      hospital admission caused by ear diseases (SIH) for each state in relation to
      their total number. The hospital admissions from each state were correlated with
      their respective IDH values. RESULTS: The state of Sao Paulo, the third largest
      IDH was responsible for 38.82% of hospital admissions caused by ear diseases,
      although its population represents 21.64% of the national population. States with
      lower IDH had lower hospital admission rates for ear diseases. CONCLUSION: SIH, a
      DATASUS tool, even with limitations, can be an instrument used to create public
      policies concerning ear diseases.

PMID- 21739014
TI  - The effect of dexamethasone on post-tonsillectomy nausea, vomiting and bleeding.
AB  - It has been stated, that the administration of Dexamethasone has an impact on the
      morbidity following tonsillectomy. OBJECTIVE: To re-calculate the blood values
      for Dexamethasone when given as fixed doses and to evaluate the effect of
      Dexamethasone on post-operative nausea, vomiting and bleeding rates following
      tonsillectomy. MATERIALS AND METHODS: The charts of 272 children (2-15 years) who
      had undergone tonsillectomy were analyzed. The rates of post-operative nausea,
      vomiting and bleeding in relation to Dexamethasone were calculated-in general and
      different doses (0 mg/kg, <0.15 mg/kg, >0.15 mg/kg). STUDY DESIGN: Retrospective
      cohort study. RESULTS: Dexamethasone was administered in 121 children (43.7%)
      according to the preference of the anesthesist (mean dose: 0.2 +/- 0.12 mg/kg;
      range: 0.04 - 0.62 mg/kg). There was no significant difference in nausea and
      vomiting (p=0.953) or bleeding (p=0.827) across groups receiving or not receiving
      Dexamethasone. Stratification into three different groups of Dexamethasone
      concentration also did not identify a dose-related risk of postoperative nausea
      or vomiting (p=0.98) or bleeding (p=0.71). CONCLUSION: At least under common non
      controlled conditions in the clinic, Dexamethasone does not appear to have an
      effect on nausea or vomiting or bleeding following tonsillectomy.

PMID- 21739015
TI  - Mucocutaneous Leishmaniasis: clinical markers in presumptive diagnosis.
AB  - Mucocutaneous Leishmaniasis (ML) can lead to serious sequela; however, early
      diagnosis can prevent complications. AIM: To evaluate clinical markers for the
      early diagnosis of ML. MATERIALS AND METHODS: A series study of 21 cases of ML,
      which were evaluated through clinical interview, nasal endoscopy, biopsy and the
      Montenegro test. RESULTS: A skin scar and previous diagnosis of cutaneous
      leishmaniasis (CL) were reported in 8(38%) patients, and 13(62%) of them denied
      having had previous CL and had no scar. Nasal/oral symptom onset until the ML
      diagnosis varied from 5 months to 20 years, mean value of 6 years. In the
      Montenegro test, the average size of the papule was 14.5 mm, which did not
      correlate with disease duration (p=0.87). The nose was the most often involved
      site and the extension of the injured mucosa did not correlate with disease
      duration. The parasite was found in 2 (9.52%) biopsy specimens. CONCLUSIONS: ML
      diagnosis was late. Finding the parasite in the mucosa, cutaneous scar and/or
      previous diagnosis of CL were not clinical markers for ML. ML diagnosis must be
      based on the Montenegro test, chronic nasal and/or oral discharge and
      histological findings ruling out other granulomatous diseases.

PMID- 21739016
TI  - Clinicopathological study of patients with head and neck sarcomas.
AB  - Sarcomas are rare tumors, mainly stemming from the embryonic mesoderm, with a
      high grade of morbidity and mortality. OBJECTIVE: To carry out a retrospective
      study of head and neck sarcoma cases between 1999 and 2008 in three specialized
      centers in the city of Fortaleza. MATERIALS AND METHODS: Data collection was
      based on the charts of the patients in the study. For statistical analysis
      purposes we used the chi-square associations and the z test for proportions.
      RESULTS: We found records of 36 patients, and the most affected ones were adult
      brown males, in the age range between 20 and 59 years--mean age of 39.7. The
      man/woman ratio was 1.76:1. The most prevalent histological type was the
      rhabdomyosarcoma and their most common locations were the face and the neck. Most
      of the sample was made up of live patients without evidence of the disease in the
      last visit--41.6% of the cases. The most common treatment modes were the
      combination of surgery + radiotherapy + chemotherapy and surgery + radiotherapy,
      with 27.8% of the cases each. CONCLUSION: Sarcomas have a great histological
      variability and may have numerous locations. Since these are rare and not well
      known lesions, new epidemiological studies must be carried out in order to
      enhance our understanding of the disease.

PMID- 21739017
TI  - Otolaryngologic manifestations in HIV disease--clinical aspects and treatment.
AB  - HIV is a pandemic infection with cases notified in almost all countries. The
      reported prevalence of symptoms in the head and neck is about 80%;
      otolaryngologists may be the first physician to see such patients. Oral
      manifestations are the most common, followed by neck and sinus manifestations.
      Otolaryngologic symptoms may be important signs of antiretroviral therapy
      failure. Symptoms are present in acute infections and advanced cases. OBJECTIVE:
      To describe new approaches in the past five years for the treatment of the most
      frequent otolaryngologic manifestations in HIV patients. METHODS: Systematic
      reviews and case series published in English and Portuguese from January 2002 to
      October 2007 including the most common otolaryngology manifestations were
      selected. CONCLUSION: Otolaryngologic manifestations are common and ENT
      specialists must be prepared to identify such cases.

PMID- 21739018
TI  - Spindle cell lipoma of the anterior triangle of the neck: a rare entity.

PMID- 21739019
TI  - A case of parotid acinic cell carcinoma in a young boy.

PMID- 21739020
TI  - Primary tuberculous osteomyelitis of the mandible mimicking a parotid fistula.

PMID- 21739022
TI  - Mandibular myofibrosarcoma of childhood: surgical resection & reconstruction with
      fibula flap.

PMID- 21739023
TI  - Evaluation of RbCl and CrCl3 as markers of Triatoma brasiliensis (Hemiptera:
      Reduviidae) nymphs: persistence and influence of Rb and Cr on triatomine biology.
AB  - In order to mark Triatoma brasiliensis, the vector of Chagas disease in Brazil,
      two chemical compounds, rubidium chloride (RbCl) and chromium chloride (CrCl3),
      were tested. First, 199 N2-N5 nymphs were fed on blood with 0.025M RbCl. Rb
      marker positivity ranged from 2.5% (N3)-70% (N2), with a maximum persistence of
      98 days. Second, 265 N2-N5 nymphs were fed on blood containing 0.0015M CrCl3. Cr
      marker positivity ranged up to 93% (N5), with a maximum persistence of 119 days.
      Finally, we blood fed 213 T. brasiliensis to investigate whether CrCl3 altered
      the biology of this insect. The developmental time of T. brasiliensis was
      unaltered, but the survival of the Cr-marked group was lower than that of the
      control group. Differences in the mean fecundity of the control (mean of 156.1)
      and experimental (mean of 135.6) groups were not statistically significant and
      100% of the egg batches of females Cr-marked as nymphs were positive. In
      conclusion, CrCl3 is a useful tool for marking T. brasiliensis nymphs due to its
      high positivity and persistence.

PMID- 21739024
TI  - An indirect immunofluorescence antibody test employing whole eggs as the antigen
      for the diagnosis of abdominal angiostrongyliasis.
AB  - Abdominal angiostrongyliasis is a potentially fatal zoonotic disease with a broad
      geographical distribution throughout Central and South America. This study
      assessed the performance of Angiostrongylus costaricensis eggs as the antigen in
      an indirect immunofluorescence assay for the determination of parasite-specific
      IgG and IgG1 antibodies. For prevalence studies, an IgG antibody titre >= 16 was
      identified as the diagnostic threshold with the best performance, providing 93.7%
      sensitivity and 84.6% specificity. Cross reactivity was evaluated with 65
      additional samples from patients with other known parasitic infections. Cross
      reactivity was observed only in samples from individuals infected with
      Strongyloides stercoralis. For clinical diagnosis, we recommend the determination
      of IgG only as a screening test. IgG1 determination may be used to increase the
      specificity of the results for patients with a positive screening test.

PMID- 21739025
TI  - An MLSA-based online scheme for the rapid identification of Stenotrophomonas
      isolates.
AB  - An online scheme to assign Stenotrophomonas isolates to genomic groups was
      developed using the multilocus sequence analysis (MLSA), which is based on the
      DNA sequencing of selected fragments of the housekeeping genes ATP synthase alpha
      subunit (atpA), the recombination repair protein (recA), the RNA polymerase alpha
      subunit (rpoA) and the excision repair beta subunit (uvrB). This MLSA-based
      scheme was validated using eight of the 10 Stenotrophomonas species that have
      been previously described. The environmental and nosocomial Stenotrophomonas
      strains were characterised using MLSA, 16S rRNA sequencing and DNA-DNA
      hybridisation (DDH) analyses. Strains of the same species were found to have
      greater than 95% concatenated sequence similarity and specific strains formed
      cohesive readily recognisable phylogenetic groups. Therefore, MLSA appeared to be
      an effective alternative methodology to amplified fragment length polymorphism
      fingerprint and DDH techniques. Strains of Stenotrophomonas can be readily
      assigned through the open database resource that was developed in the current
      study (www.steno.lncc.br/).

PMID- 21739026
TI  - Classification of immature mosquito species according to characteristics of the
      larval habitat in the subtropical province of Chaco, Argentina.
AB  - To classify mosquito species based on common features of their habitats, samples
      were obtained fortnightly between June 2001-October 2003 in the subtropical
      province of Chaco, Argentina. Data on the type of larval habitat, nature of the
      habitat (artificial or natural), size, depth, location related to sunlight,
      distance to the neighbouring houses, type of substrate, organic material,
      vegetation and algae type and their presence were collected. Data on the
      permanence, temperature, pH, turbidity, colour, odour and movement of the larval
      habitat's water were also collected. From the cluster analysis, three groups of
      species associated by their degree of habitat similarity were obtained and are
      listed below. Group 1 consisted of Aedes aegypti. Group 2 consisted of Culex
      imitator, Culex davisi, Wyeomyia muehlensi and Toxorhynchites haemorrhoidalis
      separatus. Within group 3, two subgroups are distinguished: A (Psorophora ferox,
      Psorophora cyanescens, Psorophora varinervis, Psorophora confinnis, Psorophora
      cingulata, Ochlerotatus hastatus-oligopistus, Ochlerotatus serratus, Ochlerotatus
      scapularis, Culex intrincatus, Culex quinquefasciatus, Culex pilosus,
      Ochlerotatus albifasciatus, Culex bidens) and B (Culex maxi, Culex eduardoi,
      Culex chidesteri, Uranotaenia lowii, Uranotaenia pulcherrima, Anopheles
      neomaculipalpus, Anopheles triannulatus, Anopheles albitarsis, Uranotaenia
      apicalis, Mansonia humeralis and Aedeomyia squamipennis). Principal component
      analysis indicates that the size of the larval habitats and the presence of
      aquatic vegetation are the main characteristics that explain the variation among
      different species. In contrast, water permanence is second in importance. Water
      temperature, pH and the type of larval habitat are less important in explaining
      the clustering of species.

PMID- 21739027
TI  - The effect of combined polymorphisms in chemokines and chemokine receptors on the
      clinical course of HIV-1 infection in a Brazilian population.
AB  - Polymorphisms in genes that encode chemokines or their receptors can modulate
      susceptibility to human immunodeficiency virus (HIV) infection and disease
      progression. The objective of this study was to assess the frequency of
      polymorphisms CCR5-Delta32, CCR2-64I, CCR5-59029A and SDF1-3'A and their role in
      the course of HIV infection in a Southern Brazilian population. Clinical data
      were obtained from 249 patients for an average period of 6.4 years and genotypes
      were determined by standard polymerase chain reaction (PCR) and PCR-restriction
      fragment length polymorphism. Survival analyses were conducted for three
      outcomes: CD4+ T-cell counts below 200 cells/uL, acquired immune deficiency
      syndrome (AIDS) or death. The frequency of the polymorphisms CCR5-Delta32, CCR2
      64I, CCR5-59029A and SDF1-3'A were 0.024, 0.113, 0.487 and 0.207, respectively.
      CCR5-Delta32 was associated with a reduction in the risk for CD4+ T-cell
      depletion and with an increased risk for death after AIDS diagnosis. CCR2-64I was
      associated with a reduction in the risk for developing AIDS. SDF1-3'A was also
      associated with decreased risk for AIDS, but its effect was only evident when
      CCR2-64I was present as well. These results highlight the possibility of using
      these markers as indicators for the prognosis of disease progression and provide
      evidence for the importance of analysing the effects of gene polymorphisms in a
      combined fashion.

PMID- 21739028
TI  - A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi
      is associated with increased susceptibility.
AB  - We have previously established that young male rats are more susceptible to the
      effects of Trypanosoma cruzi infection than adult rats. To explore underlying age
      associated differences in disease outcome, we simultaneously assessed hormone
      levels and cytokine release throughout the acute infection period in young and
      adult rats infected with T. cruzi. Young rats were inoculated with 1 x 10(6) and
      adult rats with 7 x 10(6) blood trypomastigotes, according to their relative body
      weight. At zero, seven, 14, 21 and 28 days after infection, blood was collected
      for the determination of gonadal and adrenal hormones, tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-10 and specific IgM and IgG subtypes. Young
      animals displayed significantly higher parasitaemia values and an endocrine
      pattern that was characterised by elevated values in corticosterone (CT) and the
      CT/dehydroepiandrosterone-sulfate ratio, which favours immunosuppression and
      susceptibility. In contrast, adult male rats were able to restrict the parasite
      burden, which likely resulted from increased IgG antibody synthesis and
      oestradiol levels. Adult rats also showed a reduced TNF-alpha/IL-10 ratio and
      less tissue damage. We conclude that young animals exhibited increased
      vulnerability to T. cruzi infection compared with adults and this is associated
      with an unsuitable immunoendocrine milieu.

PMID- 21739029
TI  - Interaction between primary and secondary sporocysts of Schistosoma mansoni and
      the internal defence system of Biomphalaria resistant and susceptible to the
      parasite.
AB  - The outcome of the interaction between Biomphalaria and Schistosoma mansoni
      depends on the response of the host internal defence system (IDS) and the escape
      mechanisms of the parasite. The aim of this study was to evaluate the
      responsiveness of the IDS (haemocytes and soluble haemolymph factors) of
      resistant and susceptible Biomphalaria tenagophila lineages and Biomphalaria
      glabrata lineages in the presence of in vitro-transformed primary sporocysts and
      secondary sporocysts obtained from infected B. glabrata. To do this, we assayed
      the cellular adhesion index (CAI), analysed viability/mortality, used fluorescent
      markers to evaluate the tegumental damage and transplanted secondary sporocysts.
      B. tenagophila Taim was more effective against primary and secondary sporocystes
      than the susceptible lineage and B. glabrata. Compared with secondary sporocysts
      exposed to B. tenagophila, primary sporocysts showed a higher CAI, a greater
      percentage of dead sporocysts and were labelled by lectin from Glycine max and
      Alexa-Fluor 488 fluorescent probes at a higher rate than the secondary
      sporocysts. However, the two B. tenagophila lineages showed no cercarial shedding
      after inoculation with secondary sporocysts. Our hypothesis that secondary
      sporocysts can escape the B. tenagophila IDS cannot be confirmed by the
      transplantation experiments. These data suggest that there are additional
      mechanisms involved in the lower susceptibilty of B. tenagophila to S. mansoni
      infection.

PMID- 21739030
TI  - Rhabdias paraensis sp. nov.: a parasite of the lungs of Rhinella marina
      (Amphibia: Bufonidae) from Brazilian Amazonia.
AB  - The nematode parasites of Rhinella marina include species of the genus Rhabdias
      (Rhabdiasidae: Rhabditoidea). The present study describes Rhabdias paraensis sp.
      nov., which parasitizes the lungs of R. marina in Brazilian Amazonia. Of the more
      than 70 known species of this genus, 18 are parasites of bufonids, of which,
      eight are Neotropical. The new species described here is similar to Rhabdias
      alabialis in the absence of lips is different by the presence of conspicuous
      cephalic papillae. We describe details of the four rows of pores, which are
      distributed equally along the whole of the length of the body and connected with
      hypodermal cells, using histology and scanning electron microscopy. Other
      histological aspects of the internal structure of this nematode are also
      described.

PMID- 21739031
TI  - Exposure of free-ranging wild carnivores, horses and domestic dogs to Leptospira
      spp in the northern Pantanal, Brazil.
AB  - Leptospirosis is a zoonotic disease affecting most mammals and is distributed
      throughout the world. Several species of domestic and wild animals may act as
      reservoirs for this disease. The purpose of this study was to assess the exposure
      of free-ranging wild carnivores, horses and domestic dogs on a private reserve
      located in the northern Pantanal (Brazil) and the surrounding areas to Leptospira
      spp from 2002-2006, 75 free-ranging wild carnivores were captured in the Pantanal
      and serum samples were collected. In addition, samples from 103 domestic dogs and
      23 horses in the region were collected. Serum samples were tested for the
      presence of Leptospira antibodies using the microscopic agglutination test.
      Thirty-two wild carnivores (42.7%) were considered positive with titres >= 100,
      and 18 domestic dogs (17.5%) and 20 horses (74.1%) were also found to be
      positive. Our study showed that horses, dogs and several species of free-ranging
      wild carnivores have been exposed to Leptospira spp in the Pantanal, suggesting
      that the peculiar characteristics of this biome, such as high temperatures and an
      extended period of flooding, may favour bacterial persistence and transmission.
      In this region, wild carnivores and horses seem to be important hosts for the
      epidemiology of Leptospira species.

PMID- 21739032
TI  - Distribution and infection of triatomines (Hemiptera: Reduviidae) by Trypanosoma
      cruzi in the state of Michoacan, Mexico.
AB  - An entomological study of triatomine species was carried out to assess their
      prevalence in 10 localities of the state of Michoacan, Mexico. Entomological
      indices were calculated to estimate the risk for vector-borne transmission of
      Trypanosoma cruzi to the human population in this area. Four triatomine species
      (Triatoma barberi, Triatoma dimidiata, Meccus pallidipennis and Meccus
      longipennis) were collected from the study area. This is the first report of M.
      longipennis and T. dimidiata in Michoacan. M. pallidipennis was significantly (p
      < 0.05) more abundant than any of the other species collected in the study area.
      Infection indices were greater than 50% for each of the four collected triatomine
      species. Significantly more triatomines were collected from intradomiciliary
      areas than from peridomiciliary or sylvatic areas. Infestation, crowding and
      density indices were low, whereas colonisation indices were high in five
      localities. The current vectorial conditions in the study area require continuous
      entomological and serological surveillance to diminish the risk of T. cruzi
      transmission to human populations.

PMID- 21739033
TI  - Monitoring temporal fluctuations of Culex quinquefasciatus using oviposition
      traps containing attractant and larvicide in an urban environment in Recife,
      Brazil.
AB  - The use of attractants and larvicides in oviposition traps is of practical
      interest for the surveillance and control of urban mosquitoes. In addition to
      increasing the safety of the traps, this combination is essential for an attract
      and-kill control strategy based on trapping mosquito eggs. The combination of
      Bacillus thuringiensis var. israelensis (Bti) and grass infusion (GI) vs. GI
      alone were tested for their ability to attract in paired BR-OVT traps in the
      backyards of 10 houses in Recife, Brazil, for a period of 45 days. Results show
      that females prefer to oviposit in traps containing Bti (363 compared with 251
      egg rafts over 45 days). Results from a one-year trial on the efficacy of BR-OVT
      traps loaded with GI and Bti as a sampling tool to monitor temporal fluctuations
      in the population densities of Culex quinquefasciatus in an urban environment are
      also reported. From December 2006-January 2007, one trap per home was installed
      and maintained for 348 consecutive days in 134-151 houses located in three urban
      blocks. Throughout the one-year field trial a total of 43,151 Culex egg rafts
      were collected in the traps. The data show that BR-OVT loaded with GI and Bti is
      sensitive enough to demonstrate continuous reproductive activity of Cux.
      quinquefasciatus in the study area throughout the year and to monitor temporal
      fluctuations in population density.

PMID- 21739034
TI  - Schistosomiasis differentially affects vasoconstrictor responses: up-regulation
      of 5-HT receptor-mediated aorta contraction.
AB  - Schistosomiasis, classified by the World Health Organization as a neglected
      tropical disease, is an intravascular parasitic disease associated to a chronic
      inflammatory state. Evidence implicating inflammation in vascular dysfunction
      continues to mount, which, broadly defined, reflects a failure in the control of
      intracellular Ca2+ and consequently, vascular contraction. Therefore, we measured
      aorta contraction induced by 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1),
      two important regulators of vascular contraction. Isometric aortic contractions
      were determined in control and Schistosoma mansoni-infected mice. In the infected
      animals, 5-HT induced a 50% higher contraction in relation to controls and we
      also observed an increased contraction in response to Ca2+ mobilisation from
      sarcoplasmic reticulum. Nevertheless, Rho kinase inhibition reduced the
      contraction in response to 5-HT equally in both groups, discarding an increase of
      the contractile machinery sensitivity to Ca2+. Furthermore, no alteration was
      observed for contractions induced by ET-1 in both groups. Our data suggest that
      an immune-vascular interaction occurs in schistosomiasis, altering vascular
      contraction outside the mesenteric portal system. More importantly, it affects
      distinct intracellular signalling involved in aorta contraction, in this case
      increasing 5-HT receptor signalling.

PMID- 21739035
TI  - Behavioural responses to human skin extracts and antennal phenotypes of sylvatic
      first filial generation and long rearing laboratory colony Rhodnius prolixus.
AB  - Chagas disease is a major public health issue and is mainly spread by Triatominae
      insects (Hemiptera: Reduviidae). Rhodnius prolixus is the main vector species in
      Northern South America. Host-seeking behaviour in R. prolixus is mediated by
      different compounds that are produced by and emanate from the host or microbiota
      on the host's skin. We tested the behavioural responses of sylvatic first filial
      generation (F1) and colony insects to extracts of human skin with a dual choice
      olfactometer. In addition, we compared the antennal phenotypes in both
      populations. No statistical differences were found between the two populations at
      the behavioural level. Both showed a preference for face and feet extracts and
      this effect was abolished for face extracts after treatment with an antibacterial
      gel. The observation of the antennal phenotype showed that there were differences
      between both groups in the total length, total surface area and number and
      density of bristles. However, the number and density of chemoreceptive sensilla
      (basiconic and thin and thick-walled trichoids) and the total density of sensilla
      did not show statistically significant differences. These results demonstrate
      that colony insects, which have only been fed with living hens for the last 30
      years, are attracted by human skin extracts in a similar way as F1 sylvatic
      insects.

PMID- 21739036
TI  - Neutralising antibodies for West Nile virus in horses from Brazilian Pantanal.
AB  - Despite evidence of West Nile virus (WNV) activity in Colombia, Venezuela and
      Argentina, this virus has not been reported in most South American countries. In
      February 2009, we commenced an investigation for WNV in mosquitoes, horses and
      caimans from the Pantanal, Central-West Brazil. The sera of 168 horses and 30
      caimans were initially tested using a flaviviruses-specific epitope-blocking
      enzyme-linked immunosorbent assay (blocking ELISA) for the detection of
      flavivirus-reactive antibodies. The seropositive samples were further tested
      using a plaque-reduction neutralisation test (PRNT90) for WNV and its most
      closely-related flaviviruses that circulate in Brazil to confirm the detection of
      specific virus-neutralising antibodies. Of the 93 (55.4%) blocking ELISA
      seropositive horse serum samples, five (3%) were seropositive for WNV, nine
      (5.4%) were seropositive for St. Louis encephalitis virus, 18 (10.7%) were
      seropositive for Ilheus virus, three (1.8%) were seropositive for Cacipacore
      virus and none were seropositive for Rocio virus using PRNT90, with a criteria of
      >= four-fold antibody titre difference. All caimans were negative for
      flaviviruses-specific antibodies using the blocking ELISA. No virus genome was
      detected from caiman blood or mosquito samples. The present study is the first
      report of confirmed serological evidence of WNV activity in Brazil.

PMID- 21739037
TI  - The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine)
      against four medically relevant Leishmania species of Brazil.
AB  - The in vitro leishmanicidal activity of miltefosine(r) (Zentaris GmbH) was
      assessed against four medically relevant Leishmania species of Brazil: Leishmania
      (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Viannia)
      guyanensis and Leishmania (Leishmania) chagasi. The activity of miltefosine
      against these New World species was compared to its activity against the Old
      World strain, Leishmania (Leishmania) donovani, which is known to be sensitive to
      the effects of miltefosine. The IC50 and IC90 results suggested the New World
      species harboured similar in vitro susceptibilities to miltefosine; however,
      miltefosine was approximately 20 times more active against the Old World L. (L.)
      donovani than against the New World L. (L.) chagasi species. The selectivity
      index varied from 17.2-28.9 for the New World Leishmania species and up to 420.0
      for L. (L.) donovani. The differences in susceptibility to miltefosine suggest
      that future clinical trials with this drug should include a laboratory pre
      evaluation and a dose-defining step.

PMID- 21739038
TI  - Ecological patterns of blood-feeding by kissing-bugs (Hemiptera: Reduviidae:
      Triatominae).
AB  - Host use by vectors is important in understanding the transmission of zoonotic
      diseases, which can affect humans, wildlife and domestic animals. Here, a
      synthesis of host exploitation patterns by kissing-bugs, vectors of Chagas
      disease, is presented. For this synthesis, an extensive literature review
      restricted to feeding sources analysed by precipitin tests was conducted. Modern
      tools from community ecology and multivariate statistics were used to determine
      patterns of segregation in host use. Rather than innate preferences for host
      species, host use by kissing-bugs is influenced by the habitats they colonise.
      One of the major limitations of studies on kissing-bug foraging has been the
      exclusive focus on the dominant vector species. We propose that expanding
      foraging studies to consider the community of vectors will substantially increase
      the understanding of Chagas disease transmission ecology. Our results indicate
      that host accessibility is a major factor that shapes the blood-foraging patterns
      of kissing-bugs. Therefore, from an applied perspective, measures that are
      directed at disrupting the contact between humans and kissing-bugs, such as
      housing improvement, are among the most desirable strategies for Chagas disease
      control.

PMID- 21739039
TI  - Full-length genomic sequence of hepatitis B virus genotype C2 isolated from a
      native Brazilian patient.
AB  - The hepatitis B virus (HBV) is among the leading causes of chronic hepatitis,
      cirrhosis and hepatocellular carcinoma. In Brazil, genotype A is the most
      frequent, followed by genotypes D and F. Genotypes B and C are found in Brazil
      exclusively among Asian patients and their descendants. The aim of this study was
      to sequence the entire HBV genome of a Caucasian patient infected with HBV/C2 and
      to infer the origin of the virus based on sequencing analysis. The sequence of
      this Brazilian isolate was grouped with four other sequences described in China.
      The sequence of this patient is the first complete genome of HBV/C2 reported in
      Brazil.

PMID- 21739040
TI  - Monitoring the circulation of rotavirus among children after the introduction of
      the RotarixTM vaccine in Goiania, Brazil.
AB  - The epidemiological features of rotavirus A (RVA) infection differ between
      children from developing and developed countries which could result in
      differences in vaccine efficacy around the world. To evaluate the impact of
      RotarixTM on RVA prevalence, we monitored RVA genotypes circulating in Goiania by
      monitoring virus in faecal samples from children that had or had not been
      previously vaccinated. From February-November of 2008, 220 faecal samples were
      collected from children in seven day-care centres. RVA detection was performed by
      two methodologies and the results were confirmed by polyacrylamide gel
      electrophoresis. From the 220 samples, eight were RVA-positive (3.6%) and five
      were from children that had received either one or two doses of the vaccine. All
      positive samples were collected from children with diarrhoea during August and
      September. Genotyping of the RVA characterised five of the viral samples as
      genotype G2P[4] and one as G8P[4], suggesting that G2P[4] was the predominant
      circulating genotype in Goiania during the study. The fact that vaccinated
      children were also infected by RVA suggests that the vaccine does not fully
      protect against infection by the G2[P4] RVA genotype.

PMID- 21739041
TI  - Genotyping of human parvovirus B19 in clinical samples from Brazil and Paraguay
      using heteroduplex mobility assay, single-stranded conformation polymorphism and
      nucleotide sequencing.
AB  - Heteroduplex mobility assay, single-stranded conformation polymorphism and
      nucleotide sequencing were utilised to genotype human parvovirus B19 samples from
      Brazil and Paraguay. Ninety-seven serum samples were collected from individuals
      presenting with abortion or erythema infectiosum, arthropathies, severe anaemia
      and transient aplastic crisis; two additional skin samples were collected by
      biopsy. After the procedure, all clinical samples were classified as genotype 1.

PMID- 21739042
TI  - Occurrence of blaOXA-23 gene in imipenem-susceptible Acinetobacter baumannii.
AB  - The aim of the current study was to describe the occurrence of the blaOXA-23 gene
      and the ISAba1 element in imipenem-susceptible Acinetobacter baumannii strains.
      By performing the polymerase chain reaction mapping using combinations of ISAba1
      forward primers and the blaOXA-23-like gene reverse primers, we demonstrated that
      the ISAba1 element did not occur upstream of the blaOXA-23 gene in five of 31
      isolates, which explained the lack of resistance to imipenem despite the presence
      of the blaOXA-23 gene. All of the blaOXA-23-positive isolates were susceptible to
      imipenem and meropenem with minimal inhibitory concentration <= 4 ug/mL. Pulsed
      field gel electrophoresis analysis revealed four genotypes among the five blaOXA
      23-positive isolates. The current report of the blaOXA-23 gene in imipenem
      susceptible isolates provided evidence that this gene may be silently spread in a
      hospital environment and highlighted the threat of undetected reservoirs of
      carbapenemase genes.

PMID- 21739043
TI  - Miltefosine induces programmed cell death in Leishmania amazonensis
      promastigotes.
AB  - In the current study, we evaluated the mechanism of action of miltefosine, which
      is the first effective and safe oral treatment for visceral leishmaniasis, in
      Leishmania amazonensis promastigotes. Miltefosine induced a process of programmed
      cell death, which was determined by the externalization of phosphatidylserine,
      the incorporation of propidium iodide, cell-cycle arrest at the sub-G0/G1 phase
      and DNA fragmentation into oligonucleosome-sized fragments. Despite the intrinsic
      variation that is detected in Leishmania spp, our results indicate that
      miltefosine causes apoptosis-like death in L. amazonensis promastigote cells
      using a similar process that is observed in Leishmania donovani.

PMID- 21739044
TI  - First report of Panstrongylus megistus sylvatic focus in municipality of Bambui,
      state of Minas Gerais, Brazil.
AB  - In 1943, the Center for the Study and Prophylaxis of Chagas Disease, Oswaldo Cruz
      Foundation, state of Minas Gerais (MG), was created in the municipality of Bambui
      to carry out studies related to Chagas disease in the mid-western region of MG.
      Since that time, several investigations have been conducted to determine the
      natural habitat of triatomines, but Panstrongylus megistus colonies have never
      been found in this region. This paper records the first finding of a P. megistus
      sylvatic colony in 69 years of research. The characteristics of this ecotope and
      its implications for the epidemiology of Chagas disease are discussed.

PMID- 21739045
TI  - [Alcohol and other drugs: actions to find solutions].

PMID- 21739046
TI  - [Epidemiological profile of drug addiction in college students].
AB  - Exploratory study with quantitative method. Data were obtained through a closed
      and structured questionnaire, self-administered to 500 undergraduates. Data
      processing and discussion was based on simple and stratified frequencies. In
      total, 185 (37.1%) students consumed or had used drugs at least once in life.
      Initial consumption started between the ages of 13 and 21 years. Alcohol is shown
      as the first drug, followed by snuff and, in descending order, marijuana,
      benzodiazepines and amphetamines. Regarding self-perception of the effect of
      drugs among users, this group showed a trend to deny that drugs exert some impact
      on their academic performance, showing that drugs use is not perceived as a
      problem if it affects only themselves, but is perceived as a problem if affecting
      fellow students when consuming drugs.

PMID- 21739047
TI  - [Risk and protection factors related to the consumption of psychoactive
      substances in undergraduate nursing students].
AB  - This study aims to identify the frequency of risk and protection factors related
      to drug consumption among undergraduate nursing students. It is a cross-sectional
      study in which authors applied the instrument Risk and Protection Factors for the
      Consumption of Psychoactive Substances, validated for use with undergraduate
      nursing students. Data were analyzed through STATA 10. Three hundred and ninety
      students participated in the study. The domain "prejudice and appraisal", "social
      permissiveness and access to psychoactive substances", "social skills and self
      control" are risk factors for drugs use in 100% of participants. "Spirituality"
      and "satisfaction with interpersonal relations" were predominant protective
      domains. Based on data, authors can conclude that the students did not consider
      the risks in alcohol and tobacco consumption, as they think it is normal and
      socially acceptable.

PMID- 21739048
TI  - [Nursing school students' perception of legal and illegal drugs consumption].
AB  - Drugs consumption is as ancient as humanity. It has always existed and is
      associated with culture, in its historical and social context. The aim of this
      research is to know and analyze the perception of students from the Nursing
      School at the University of Guayaquil about legal and illegal drugs consumption.
      The methodological approach was qualitative, descriptive and exploratory. The
      sample consisted of eleven first-year students from the Nursing School.
      Individual and semi structured interviews were used for data collection. Thematic
      content analysis was adopted, in which five themes were identified: The economic
      situation, domestic violence, migration of close relatives, influence of the
      media that surround us, and ignorance about the topic. With a view to enhancing
      awareness on this hard reality that hurts and prejudices humanity, knowing
      students' perceptions contributes to identify their needs and create
      possibilities for health care interventions, particularly health promotion.

PMID- 21739049
TI  - [Experiences and meanings of the drugs phenomenon in nursing students].
AB  - The aim of this study was to identify the meanings and experiences of nursing
      students regarding the drugs phenomenon. Data were collected through a semi
      structured interview. Data analysis showed five theme categories. Of the 40
      subjects in the sample, between 19 and 24 years old, 28 were women. Three had
      never received information about drugs, and most had had experiences with
      consumers or had consumed drugs. In Costa Rica, this problem is associated with
      stigma and traffic. They recognize that everyone is responsible, and consent with
      the State's contradictory attitude through tobacco company advertisements and
      complicity with distilleries. They acknowledge the importance of prevention and
      consider that the current approach of this issue is not appropriate. They would
      like it to be incorporated in their education, providing strategies on how to act
      and relate with drugs consumers.

PMID- 21739050
TI  - [Bolivian university students' view of alcohol use in the university context].
AB  - Qualitative research inquiring into the university world about the values of
      young people's life to successfully offset the danger of alcohol consumption.
      Discussion groups were implemented in workshops with 46 university students. The
      results show that that Bolivian society is very tolerant and permissive towards
      alcohol consumption by male university students. Values like pride, self-respect,
      responsibility and capacity for reflection constitute a framework of regulatory
      action, but it is not generalized.

PMID- 21739051
TI  - [Licit drugs consumption among nursing students at a private university in
      Bogota, Colombia].
AB  - This cross-sectional study aimed to establish the consumption of licit
      psychoactive substances in a sample of 237 nursing students at a private
      university in the city of Bogota, Colombia; and relate it with independent study
      variables: age, sex, marital status, semester, number of children, work and
      living together. Fagerstrom's Tolerance questionnaire was used to evaluate the
      gravity of nicotine dependence and the AUDIT to evaluate alcohol dependence.
      Confidentiality was guaranteed through the self administered Questionnaire and
      anonymous survey. Univariate analysis was used. Relevant data in this population
      was tobacco consumption in about 24 % and alcohol in 82%. The level of tobacco
      dependence corresponded to 5 (8.5%) students with slight dependence, 42 (72%)
      with average dependence and 12 (20%) with high dependence. When relating tobacco
      and alcohol consumption, 98 % of the students who smoke consume alcohol. The
      percentage of students who never drink was higher in the group of non smokers
      (23%) than among smokers (1.72%).

PMID- 21739052
TI  - [Alcohol use among Mexican medical students].
AB  - The study aims to identify patterns of alcohol consumption in Mexican medical
      students. This is a cross-sectional study, conducted at the University of
      Veracruz, Mexico. The sample comprised 263 students (84.4%). The Alcohol Use
      Disorders Identification Test and the Student Questionnaire 2006 were used.
      Students were characterized by youth and women. Seventy-two percent used alcohol
      in the lifetime, with 12.5 years as the onset age. The frequency of consumption
      was low but the quantity high, with a pattern of drunkenness, mainly among men.
      Forty-six percent consumed beverage at a problematic level. Students perceive
      that parents and teachers badly assess alcoholic beverage consumption. This study
      contributes to the planning of preventive programs for alcohol consumption, to be
      applied in the university context.

PMID- 21739053
TI  - [Knowledge on drugs phenomenon by students and faculty from the Medical School at
      Universidad Mayor de San Andres, La Paz, Bolivia].
AB  - The goal of this study was to identify the degree of knowledge of students and
      health educators on licit and illicit drugs, related to the type, classification,
      action, mechanisms damages, consequences and adverse effects, besides use and
      consumption. A cross-sectional methodological design was used, with a sample of
      172 students, professors and residents in medicine and nursing at Universidad
      Mayor de San Andres (UMSA), Bolivia. The results reveal weak knowledge on the
      classification of psychotropic substances according to structure, chemical
      property and effects for health, highlighting significant difference with
      knowledge on licit and illicit drugs use, with high percentages. In conclusion,
      there is lack of knowledge in all groups studied on licit and illicit drugs
      regarding the consequences and adverse effects. This confirms the need to improve
      teaching on this content in health schools.

PMID- 21739054
TI  - [Smoking among college students: characterization of use in the students'
      perspective].
AB  - The aim was to determine the meanings attributed to tobacco consumption among
      freshmen college students at the University of Tegucigalpa, Honduras. A
      qualitative study was carried out, using symbolic interactionism as the
      methodological framework. We conducted four focus groups with 10 to 12 male and
      female students from different courses, smokers and nonsmokers. The main
      categories of meanings regarding tobacco use were the presence of smokers in
      families of origin, the spaces for the start of smoking. The reasons for the
      initiation of tobacco use include influence from friends and colleagues. Sports
      and personal commitments were considered factors that do not promote tobacco use.
      We concluded that the university is an open space for the development and
      implementation of educational strategies in the prevention against tobacco use.

PMID- 21739055
TI  - [Protective and family risk factors related to adolescent drug use].
AB  - This cross-sectional and quantitative study aimed to verify the family's
      protective and risk factors related to drugs use in adolescents, considering the
      interaction patterns developed in the family, their degree of adaptability and
      vulnerability. Participants in this study were 80 female adolescents, from the
      1st to 4th grade of high school, who answered a questionnaire. The most relevant
      risk and protective factors that would influence the situation were established,
      such as patterns of interaction, degree of adaptability, way of coping with
      problems, family resources and values. The major risk factors that emerged were
      the way people confront problems and, within these, lack of religious support and
      professional support, besides communication difficulties within families. The
      lowest risks were values, such as personal effort. The results highlight that
      nurses should assume psychosocial interventions as part of their role, especially
      among school-age children as, thus, they would be acting as agents in the
      prevention of drugs use.

PMID- 21739056
TI  - [Meaning of drugs use for adolescents living in the streets, Valencia,
      Venezuela].
AB  - This descriptive study with a qualitative approach aims to reveal the meaning of
      drugs use among adolescents living in the street, a condition that turns them
      into a social problem, so that theoretical approach seeks to understand the
      phenomenon. Seven (7) female adolescents living on the Cabriales walk in
      Valencia, Venezuela were interviewed. Grounded Theory and symbolic interactionism
      were used for data processing. Thus, the following categories were noticed: The
      search not to be good, Reaffirmation of the role of women, Consumption as
      experience, The gaze of others to the adolescent who uses drugs and The addict as
      a caregiver. Finally, we found that the use of drugs on the street for girls is a
      form of protection, survival and inclusion in the group.

PMID- 21739057
TI  - [Relations between family context and substance abuse in high school
      adolescents].
AB  - This study aimed to describe the family context characteristics of high school
      adolescents and their relation to psychoactive substance abuse. It is a cross
      sectional and descriptive study, with a population of 657 secondary-school
      students in the city of Leon, Nicaragua, which corresponded to 31% of the
      research context. Data was collected through an anonymous questionnaire. Results
      show that 56% of the adolescents were living with both parents and 32% only with
      the mother, 86% declared a good relationship with the mother, but 24% did not
      show confidence in the mother figure. Regarding psychoactive substance use within
      the family context, 52% of the adolescents' family presented previous use events
      and, in 42% of cases, the father was the user. Results offer important
      contributions to design public healthcare policies and to outline prevention
      strategies for use among adolescents.

PMID- 21739058
TI  - [International cooperation in combatting illicit drugs in Mozambique].
AB  - Countries from Southern Africa have formed a Development Community (SADC) to
      stimulate common actions in several areas, among them illicit drugs combat. In
      this context, the goal of this qualitative study was to identify information and
      perception about the cooperation set up between Mozambique and other SADC members
      in combatting illicit drugs. Data were collected through semi-structured
      interviews with public employees developing actions directed at the
      implementation of the Protocol to Combat Drugs in SADC. After transcriptions, the
      interviews were analyzed by content analysis and resulted in the categories:
      "Mozambique as a drugs corridor", "Cooperation Initiatives on Drugs among African
      countries", "Cooperation Difficulties in Africa", "Problems in Protocol
      Implementation" and "Difficulties to implement a control policy". As a
      consequence, there is a need to review and update the policies and strategies in
      the drugs area, as they are not contextualized in the country's current reality.

PMID- 21739059
TI  - [Social risk factors for alcohol use among adolescents and youth].
AB  - This study examines the social risk and protection factors for excessive alcohol
      use, based on the data from the "National Survey on the prevalence of substance
      abuse in 2008", in a population of young Argentines, from 16 to 24 years of age.
      Bivariate and multivariate analyses were used. The following risk factors were
      observed: age at onset (the younger, the higher the risk); the Pampas region,
      Northwest and Northeast; males; from families with unsatisfied basic needs.
      Protective factors include idleness, no opportunity to try out illicit drugs, not
      being tempted to experiment with illicit drugs and no previous use of tobacco, or
      tranquilizers, or cocaine or cocaine-based substances in the lifetime. The
      results provide useful information to develop prevention programs for adolescents
      and young people.

PMID- 21739060
TI  - [School spaces for the prevention of drug addiction: view of school principals].
AB  - The aim of this research was to analyze the Secondary School Managers' response
      to the availability of a physical and psychological space at school to work on
      drug addiction prevention. A semi-structured questionnaire was applied to a
      sample of 15 high school managers in the Argentinean Education System (public and
      private schools) in Buenos Aires city and in the Province of Buenos Aires. A
      qualitative survey was carried out within the theoretical framework of
      International Health Regulations, School Management, Social Psychology and formal
      school regulations. These managers assume that the prevention of drug addiction
      should be addressed at school, with the support of other institutions and
      experts. The main objective should be to promote professional training in health,
      psychology and group dynamics and to create a warm environment at school, based
      on empathy, understanding and tolerance to strengthen the bond with the students.

PMID- 21739061
TI  - [Protective and family risk factors related to drugs in families of adolescents
      from Valparaiso, Chile].
AB  - This quantitative, cross-sectional, descriptive and exploratory research aimed to
      identify and describe protective and family risk factors related to the
      phenomenon of drugs in adolescents' families in the community of Valparaiso,
      Chile. The sample consisted of 61 students enrolled in 2008 and selected through
      simple random sampling. The data collection instrument was a questionnaire,
      developed and validated by experts from five countries in the Americas. Of the
      adolescents, 86.9% perceived the family relations, in general, as a protective
      factor, highlighting great communication with parents. Tensions, health and
      behavior problems were found as protective factors by a small number of students
      who act as neutral actors, in both cases associated with alcohol and drugs
      consumption by some family member. As risk factors, education and parents' kind
      of work were appointed.

PMID- 21739062
TI  - [The view of adolescents from the rural area of Costa Rica in rehabilitation
      programs about drug consumption].
AB  - This qualitative study aimed to investigate the view of adolescents following
      rehabilitation programs about the consumption of illicit drugs. It was carried
      out in two Non-Governmental Organizations in Costa Rica. The focus group
      technique was applied, aiming to allow adolescents to express their feelings and
      experiences regarding illicit drug consumption. Results showed that the
      perception adolescents have of themselves is focused on a process of change and
      development of their identity and experimentation, which influence them in taking
      negative decisions like drug consumption. The relationships they have with their
      parents are conflicting, as they come from dysfunctional homes and marginal
      communities. Friends represent support for their difficulties and lead to drug
      consumption. The state of Costa Rica needs to define public policies to improve
      the lives of this population.

PMID- 21739063
TI  - [Comparison between crack and other drugs abusers in a specialized outpatient
      facility of a university hospital].
AB  - The increase in crack abuse and the profile of these abusers are well documented
      in Brazil, but studies in Rio de Janeiro are lacking. Optimization of resource
      allocation for prevention and treatment requires a better characterization of
      abusers with respect to socio-demographic characteristics and drugs use pattern.
      Patients admitted to the Drug Abuse Research and Care Program (PROJAD) at the
      Psychiatric Institute of the Federal University of Rio de Janeiro between March
      2007 and September 2008 were studied. Crack abusers were found to be
      significantly younger than other drug abusers and more frequently unmarried.
      Lower education level and unemployment were a trend in this group, although not
      statistically significant. The increase in the number of patients seeking
      treatment for crack abuse was documented. This is the first scientific study
      reporting on the expansion of crack abuse in Rio de Janeiro, which may provide
      information to put in practice public policies.

PMID- 21739064
TI  - [Implementation of brief intervention for problematic alcohol use in primary
      health in the Amazon context].
AB  - AIMS: to evaluate the implementation process of Screening and Brief Interventions
      for the Problematic Use of Alcohol (PUA) in primary health care in the city of
      Coari, Amazonas. METHODS: management evaluation through a process analysis study,
      using triangulation methods, with qualitative techniques like focus groups with
      health professionals and with the training/follow up team; quantitative
      epidemiological data and data concerning health service productivity in 2008.
      RESULTS: the health team accepted the training course well, feeling that it
      valued them. Twenty-five percent of the sample scored PUA using AUDIT.
      Difficulties: preservation of the biomedical approach, difficulties to continue
      the work because of high professional rotation levels due to political reasons,
      difficulties to stabilize policies in places with little access. CONCLUSIONS:
      management action is needed, as well as health policies for PUA in the PHC,
      including the need for fixed human resources in PHC teams.

PMID- 21739065
TI  - [Community therapy as a method to address the problem of alcohol abuse in primary
      care].
AB  - This study aimed to identify the potential of community therapy (CT) as a method
      to address the problem of alcohol abuse in primary care from a user perspective.
      This study was carried out at the headquarters of the Quatro Varas Project,
      Fortaleza-CE, Brazil. This qualitative, ethnographic study used semi-structured
      interview and participant observation. Of the 20 interviewed participants, one
      was chosen for an in-depth interview. Two thematic units were constructed: the
      effects of the therapy on alcoholism and therapy as a social support resource for
      problems related to alcohol use. Results indicate that the dialogue established
      during therapy promotes re-signification of the problem and redirects the therapy
      course towards management of one's own life and search for citizenship. We
      concluded that CT favors the elaboration of a network of systemic relationships
      that broaden the understanding of problems caused by alcoholism and is an
      effective strategy to address the problem in the community health sphere.

PMID- 21739066
TI  - [Prevention and monitoring strategies on the use of illicit substances and
      accidents and costs in heavy load drivers in Mexico].
AB  - Road crashes are one of the largest public health problems in the world. Impacts
      affect Health, Economic and Social areas. This study focuses on heavy load
      drivers. The goal is to identify the costs of accidents to implement control
      strategies for licit and illicit substance consumption in heavy load drivers.
      METHOD: a retrospective correlation study was conducted, covering the period from
      2004 to 2006. In the population covered by the program, the number of accidents
      decreased by 15% and cost for damage by collision by 24%. CONCLUSION: This type
      of studies are of great value and can be used as a basis for implementing
      programs designed to modify behavior and carefully monitor the health of
      professional drivers.

PMID- 21739067
TI  - [Drugs use as a cultural practice within gangs].
AB  - Today, the social phenomenon of drugs trafficking and violence related to drugs
      has tended to minimize the implications of drugs consumption in gangs. This
      article is based on in-depth interviews in young gangs in the metropolitan area
      of Nuevo Leon, Mexico, with a view to reflecting on and analyzing the drug as a
      cultural practice within gangs. In the search for meaning, the first thing that
      is shown is the beginning of gang members in drugs consumption, and the form how
      drugs are presented by family members and friends of the gang is described. Next,
      we described the meaning of drugs use in everyday life and show the extent to
      which drugs use is acceptable and normalized.

PMID- 21739068
TI  - Nutritional intervention and the impact on adherence to treatment in patients
      with metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome is associated with increased risk of
      cardiovascular events disease and type 2 diabetes. Treatment includes
      modifications on life style, diet and physical activity. Treatment adherence
      plays a crucial role in the successful treatment of this disease. OBJECTIVE: To
      evaluate two models of dietary intervention, and the relationship with adherence
      to treatment and impact on clinical improvement of patients with metabolic
      syndrome. METHODS: Randomized clinical trial, lasting four months. Participants
      were randomized assigned to the intervention or control group. Both groups were
      instructed to follow a diet for 4 months. Subjects in the intervention group
      additionally received an intervention package, with metabolic syndrome manual
      book, telephone counseling and nutrition education leaflets. In both groups
      nutritional anamnesis, anthropometric assessment, dietary assessment,
      individualized dietary and biochemical tests were done. RESULTS: Patients who
      arrived more motivated were those who has the greatest reduction in the values of
      body mass index, which decreased from 31.7 kg/m2 (SD +/- 3.9) to 30.9 kg/m2 (SD
      +/- 3.8), reduction in waist circumference was 108.1 cm (SD +/- 9.8) to 105.9 cm
      (SD +/- 9.5). The statistically significant associations were in the correlation
      between body mass index, blood glucose and triglycerides, reducing the
      consumption of whole milk, increased consumption of whole grains and skimmed milk
      and between the increase in vegetable intake and reducing triglycerides.
      CONCLUSION: Both groups showed significant improvement in all clinical parameters
      that was significantly associated with the previous motivation. Patients who
      arrived more motivated were those who responded better to treatment.

PMID- 21739069
TI  - Validity of maximum heart rate prediction equations for children and adolescents.
AB  - BACKGROUND: There are no studies in the literature to validate equations that
      predict maximum heart rate (HRmax) in children and adolescents. OBJECTIVE: To
      analyze the validity of the HRmax predictive equations "220 - age" and "208 -
      (0.7 x age)" in boys aged 10 and 16. METHODS: A progressive maximal exertion test
      was carried out in 69 apparently healthy boys aged 10 to 16. The initial test
      velocity was 9 km/h, with 1-km/h increments every three minutes. The test was
      maintained until maximum voluntary exertion was achieved, considering HRmax as
      the highest heart rate attained during the test. The measured HRmax was compared
      with the values predicted by the "220 - age" and "208 - (0.7 x age)" equations,
      using ANOVA for repeated measures. RESULTS: The mean values of HRmax (bpm) were:
      200.2 +/- 8.0 (measured), 207.4 +/- 1.5 ("220 - age") and 199.2 +/- 1.1 ("208 -
      (0.7 x age)"). The HRmax predicted by the "220 - age" equation was significantly
      higher (p < 0.001) than the measured HRmax and the HRmax predicted by the ("208 -
      (0.7 x age)") equation. The correlation between the measured HRmax and age was
      not statistically significant (r = 0.096; p > 0.05). CONCLUSION: The "220 - age"
      equation overestimated the measured HRmax and was not valid for this population.
      The "208 - (0.7 x age)" equation was valid for this population, showing results
      that were quite similar to those of measured HRmax. Future studies with larger
      sample sizes can verify whether the HRmax does not depend on age for this
      population, a situation in which the constant 200 bpm value would be more
      appropriate for HRmax.

PMID- 21739070
TI  - Chagas disease in the State of Pernambuco, Brazil: analysis of admissions and
      mortality time series.
AB  - INTRODUCTION: A time series study of admissions, deaths and acute cases was
      conducted in order to evaluate the context of Chagas disease in Pernambuco.
      METHODS: Data reported to the Information Technology Department of the Brazilian
      National Health Service between 1980 and 2008 was collected for regions and
      Federal Units of Brazil; and microregions and municipalities of Pernambuco. Rates
      (per 100,000 inhabitants) of hospitalization, mortality and acute cases were
      calculated using a national hospital database (SIH), a national mortality
      database (SIM) and the national Information System for Notifiable Diseases
      (SINAN), respectively. RESULTS: The national average for Chagas disease
      admissions was 0.99 from 1995 to 2008. Pernambuco obtained a mean of 0.39 in the
      same period, with the highest rates being concentrated in the interior of the
      state. The state obtained a mean mortality rate of 1.56 between 1980 and 2007,
      which was lower than the national average (3.66). The mortality rate has tended
      to decline nationally, while it has remained relatively unchanged in Pernambuco.
      Interpolating national rates of admissions and deaths, mortality rates were
      higher than hospitalization rates between 1995 and 2007. The same occurred in
      Pernambuco, except for 2003. Between 2001 and 2006, rates for acute cases were
      0.56 and 0.21 for Brazil and Pernambuco, respectively. CONCLUSIONS: Although a
      decrease in Chagas mortality has occurred in Brazil, the disease remains a
      serious public health problem, especially in the Northeast region. It is thus
      essential that medical care, prevention and control regarding Chagas disease be
      maintained and improved.

PMID- 21739071
TI  - Nutritional assessment and lipid profile in HIV-infected children and adolescents
      treated with highly active antiretroviral therapy.
AB  - INTRODUCTION: HIV-infected children and adolescents treated with highly active
      antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI)
      can show significant improvements in clinical outcomes, nutritional status and
      quality of life. The study aimed to report nutritional and metabolic alterations
      for pediatric patients continuously exposed to HAART and for healthy controls for
      up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake
      data were collected prospectively over approximately 12-months for each patient.
      RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12
      months follow-up, HIV-positive individuals remained below the healthy control
      group parameters. No change was observed concerning food intake. Triglyceride
      serum levels were higher in patients using protease inhibitor at the onset of the
      study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5
      (20 - 162); p = 0.003], but after twelve months follow-up, only the group using
      protease inhibitor for up to two months presented higher values [140 (73 - 273)
      versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive
      individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34
      - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated
      with highly active antiretroviral therapy showed compromised nutritional
      parameters compared to a paired healthy control group. Individuals using protease
      inhibitor presented worse triglyceride serum levels compared to their healthy
      counterparts.

PMID- 21739072
TI  - Seroepidemiological study of human cysticercosis with blood samples collected on
      filter paper, in Lages, State of Santa Catarina, Brazil, 2004-2005.
AB  - INTRODUCTION: Human serofrequency of antibodies against Taenia solium antigens
      was determined and risk factors for cysticercosis transmission were identified.
      METHODS: Individuals (n=878) from periurban and rural locations of Lages, SC,
      were interviewed to gather demographic, sanitary and health information.
      Interviews and blood sample collections by finger prick on Whatman filter paper
      were performed from August 2004 to May 2005. Observation determined that 850
      samples were suitable for analysis and were tested by ELISA using vesicular fluid
      of Taenia crassiceps heterologous antigen. To ensure the reliability of the
      results, 77 samples of the dried blood were matched with sera. The reactive
      samples were submitted to a serum confirmatory immunoblot (IB) test using
      purified Taenia crassiceps glycoproteins. RESULTS: The ELISA results for the
      dried blood and serum samples were statistically consistent. ELISA was positive
      in 186 (21.9%) out of 850 individuals. A group of 213 individuals were asked to
      collect vein blood for IB (186 with positive result in ELISA and 27 with
      inappropriate whole blood samples) and 130 attended the request. The IB was
      positive in 29 (3.4%) out of 850 individuals. A significant correlation (p =
      0.0364) was determined among individuals who tested positive in the IB assay who
      practiced both pig rearing and kitchen gardening. CONCLUSIONS: ELISA with dried
      blood eluted from filter paper was suitable for cysticercosis population surveys.
      In Lages, human infection was associated with pig rearing and kitchen gardening.
      The prevalence index was compatible with other Latin American endemic areas.

PMID- 21739073
TI  - Reemergence of yellow fever: detection of transmission in the State of Sao Paulo,
      Brazil, 2008.
AB  - INTRODUCTION: Following yellow fever virus (YFV) isolation in monkeys from the
      Sao Jose do Rio Preto region and two fatal human autochthonous cases from the
      Ribeirao Preto region, State of Sao Paulo, Brazil, two expeditions for
      entomological research and eco-epidemiological evaluation were conducted.
      METHODS: A total of 577 samples from humans, 108 from monkeys and 3,049
      mosquitoes were analyzed by one or more methods: virus isolation, ELISA-IgM, RT
      PCR, histopathology and immunohistochemical. RESULTS: Of the 577 human samples,
      531 were tested by ELISA-IgM, with 3 positives, and 235 were inoculated into mice
      and 199 in cell culture, resulting in one virus isolation. One sample was
      positive by histopathology and immunohistochemical. Using RT-PCR, 25 samples were
      processed with 4 positive reactions. A total of 108 specimens of monkeys were
      examined, 108 were inoculated into mice and 45 in cell culture. Four virus
      strains were isolated from Alouatta caraya. A total of 931 mosquitoes were
      captured in Sao Jose do Rio Preto and 2,118 in Ribeirao Preto and separated into
      batches. A single isolation of YFV was derived from a batch of 9 mosquitoes
      Psorophora ferox, collected in Urupes, Ribeirao Preto region. A serological
      survey was conducted with 128 samples from the municipalities of Sao Carlos,
      Rincao and Ribeirao Preto and 10 samples from contacts of patients from Ribeirao
      Preto. All samples were negative by ELISA-IgM for YFV. CONCLUSIONS: The results
      confirm the circulation of yellow fever, even though sporadic, in the Sao Paulo
      State and reinforce the importance of vaccination against yellow fever in areas
      considered at risk.

PMID- 21739074
TI  - [Behavior of immatures Aedes aegypti in the coast State of Sao Paulo, Brazil].
AB  - INTRODUCTION: In a region of high dengue incidence, on the coast of the State of
      Sao Paulo, 9 areas were selected to evaluate the behavior of immature Aedes
      aegypti. METHODS: The 9 areas were grouped into 4 strata according to soil use
      and occupation. Larvae and pupas were collected in a sample of approximately 500
      buildings in each area. RESULTS: Although tires and canvas presented the highest
      positive rates for Aedes aegypti, drains and other containers fixed to the
      buildings were highly predominant among positive containers; 32 to 76% of the
      positive containers in the 4 study strata. Public areas of apartment buildings
      and large non-residential premises presented the highest positive rates for Aedes
      Aegypti, while apartments presented the lowest. Infestation levels were greater
      in residential areas with predominance of apartment buildings, where 76% of the
      breeding sites detected were containers fixed to the buildings. CONCLUSIONS: This
      knowledge is an important tool in the control strategy, since it reinforces the
      need for special attention regarding certain types of buildings and the
      adjustment of technical norms for pluvial water drains and improvement of
      building maintenance. Moreover, systematic observations are required to follow-up
      the occupancy dynamic of different buildings and containers by Aedes aegypti and
      the incorporation of this knowledge in the control of vectors in the region.

PMID- 21739075
TI  - Prevalence of cholelithiasis in patients with chagasic megaesophagus.
AB  - INTRODUCTION: The prevalence of cholelithiasis in the general population ranges
      from 9 to 18%. This prevalence is known to be higher in the presence of
      parasympathetic nerve damage of the biliary tract either due to surgery
      (vagotomy) or neuronal destruction (Chagas disease). The objective of this study
      was to evaluate the association of cholelithiasis and chagasic or idiopathic
      megaesophagus. METHODS: The ultrasound scans of 152 patients with megaesophagus
      submitted to cardiomyotomy and subtotal esophagectomy surgery were evaluated. The
      presence of cholelithiasis was compared between chagasic and idiopathic
      esophagopathy and ultrasound and clinical findings were correlated with age, sex
      and race. RESULTS: A total of 152 cases of megaesophagus, including 137 with
      chagasic megaesophagus and 15 with idiopathic megaesophagus, were analyzed. The
      mean age was 56.7 years (45-67) in the 137 patients with chagasic megaesophagus
      and 35.6 years (27-44) in the 15 cases of idiopathic megaesophagus, with a
      significant difference between the two groups (p < 0.0001). The group with
      chagasic megaesophagus consisted of 59 (43%) women and 78 (56.9%) men, while the
      group with idiopathic megaesophagus consisted of 8 (53.3%) women and 7 (46.6%)
      men, showing no significant difference between the groups. Of the 137 patients
      with confirmed chagasic megaesophagus, 39 (28.4%) presented cholelithiasis versus
      one case (6.6%) in the 15 patients with idiopathic megaesophagus. CONCLUSIONS:
      The prevalence of cholelithiasis is high in patients with chagasic megaesophagus
      and preoperative ultrasound should be performed routinely in these patients in
      order to treat both conditions during the same surgical procedure.

PMID- 21739076
TI  - Homicide victimization according to racial characteristics in Brazil.
AB  - OBJECTIVE: To describe the temporal patterns of mortality by homicide in Brazil.
      METHODS: A series of homicides in Brazil from 2000 to 2009 were studied. The
      explanatory variables were race/skin color, gender and education. The death
      statistics were obtained from the Mortality Information System. A trend analysis
      was performed by means of a polynomial regression for a historic time series (p <
      0.05, 95% confidence interval). RESULTS: The black population represented 69% of
      the homicide victims in 2009. The homicide rate increased in the black
      population, while it decreased in the white population in the period studied. The
      homicide rate increased in groups with both higher and lower education among
      blacks; among whites, the rate decreased for those with the lowest level of
      schooling and remained stable in the group with higher educational levels. In
      2009, blacks had a higher risk of death than whites from homicide, regardless of
      education level. Between 2004 and 2009, the homicide rate decreased in the white
      population, while it increased in the black population. CONCLUSIONS: The relative
      risk of falling victim to homicide increased in the black population, suggesting
      an increase in inequality. The effect of the anti-gun measures implemented in
      Brazil in 2004 was positive in the white population and less pronounced in the
      black population. Overall, race/skin color predicted the occurrence of homicide.

PMID- 21739077
TI  - A technical analysis of medicines request-related decision making in Brazilian
      courts.
AB  - OBJECTIVE: To analyze judicial requests for medications that are covered by the
      pharmaceutical assistance components of the Sistema Unico de Saude (SUS -
      Brazilian Unified Health System). METHODS: We analyzed 81 judicial requests for
      medications in the State of Sao Paulo between 2005 and 2009. The details of these
      cases were obtained electronically from the Court of Justice of the State of Sao
      Paulo. Directives that regulate pharmaceutical assistance were consulted to
      identify judicially requested medications that are covered by the SUS. To assess
      the level of evidence supporting the use of these medications to treat the
      clinical indications described, we consulted the Thomson Micromedex(r) database.
      RESULTS: The number of individual medications requested in each case ranged from
      1 to 7; in total, 77 different pharmaceuticals agents were identified. Of the
      medications requested, 14.3% should have been available through SUS primary care,
      19.5% were classified under the exceptionally dispensed medications component of
      the SUS, and 66.2% were not on any official list. Medications of the
      exceptionally dispensed medications component showed better clinical evidence
      when indicated for the treatment of medical conditions covered by the Clinical
      Protocols and Therapeutic Guidelines of Brazil's Ministry of Health. CONCLUSIONS:
      The judicial process has been used to ensure access to medications that are
      covered by the SUS and to request access to those that are not covered. Our
      assessment of the level of available evidence reinforces the need for technical
      analysis in the decision-making process in cases of judicially requested
      medications.

PMID- 21739078
TI  - Factors associated to relapse of leprosy in Mato Grosso, Central-Western Brazil.
AB  - OBJECTIVE: To analyze factors associated with relapse of leprosy. METHODS:
      Retrospective case-control study including 159 patients older than 15 diagnosed
      with leprosy attending reference centers for leprosy in five municipalities in
      the state of Mato Grosso, central-western Brazil. Cases (n=53) were patients with
      relapsed leprosy diagnosed from 2005 to 2007 who were compared with controls
      (n=106) matching for gender and operational classification who were considered
      cured after treatment in 2005. Data was obtained from the local Notifiable
      Diseases Database, medical records and interviews. For the analyses conditional
      logistic regression and hierarchical approaches were used. RESULTS: After
      adjustment, the following factors were associated with relapse of leprosy: living
      in rental housing (OR = 4.1; 95%CI: 1.43;12.04); living in houses constructed of
      wood and mud (OR = 3.2; 95%CI: 1.16;8.76); living with dwellings with more than
      five people (OR = 2.1; 95%CI: 1.03;4.36); alcohol use disorder (OR = 2.8; 95%CI:
      1.17;6.79); irregular treatment (OR =3.8; 95%CI: 1.44;10.02); lack of knowledge
      about the disease/treatment (OR = 2.6; 95%CI: 1.09;6.13); use of public
      transportation to get to the clinic (OR = 5.5; 95%CI: 2.36;12.63); clinical form
      of the disease (OR = 7.1; 95%CI: 2.48;20.52), and treatment regimen (OR = 3.7;
      95%CI: 1.49;9.11). CONCLUSIONS: The predictive factors of relapse are associated
      with housing conditions, living habits, organization of health services, clinical
      forms of leprosy and treatment regimen. Health services should educate patients
      on the disease as well as ensure consistent treatment.

PMID- 21739079
TI  - Rational therapeutics: health-related elements in lawsuits demanding medicines.
AB  - OBJECTIVE: To characterize the main medical, scientific and health-related
      procedural elements upon which decisions are made in individual lawsuits
      demanding medicines that are considered essential to the Court of Justice.
      METHODS: Retrospective descriptive study based on 27 cases ruled on by the Court
      of Appeals in Rio de Janeiro, Southeastern Brazil, in 2006. The original
      proceedings were solicited from the Central Archive of the Court of Justice of
      the State of Rio de Janeiro and were photographed and analyzed in full. RESULTS:
      Prescriptions and medical certificates were present in 100% of the lawsuits. All
      prescriptions lacked conformity to legislation. No expert medical reports were
      added, and only 7.4% of the lawsuits presented complementary examinations. In
      spite of the scarcity of medical information present in the records, all of the
      demands were granted. CONCLUSIONS: The admission of judicial demands devoid of
      clinical and diagnostic substantiation results in managerial and health-related
      constraints on the health system. Besides creating havoc in standard
      pharmaceutical services, badly justified medicine demands may compromise rational
      drug use.

PMID- 21739080
TI  - HIV prevalence in pregnant women and vertical transmission in according to
      socioeconomic status, Southeastern Brazil.
AB  - OBJECTIVE: To describe HIV prevalence in pregnant women and the rate of vertical
      transmission according to socioeconomic status of residential neighborhoods.
      METHODS: Ecological exploratory study, which used the Information System of
      Notifiable Diseases database on HIV-positive pregnant women and AIDS in children,
      reported from 2000 to 2006, in Vitoria, Southeastern Brazil. For analysis of
      socioeconomic data the Urban Quality Index was utilized The HIV prevalence rate
      in pregnant women and vertical transmission rate were calculated. Spatial
      distribution was carried out by Terraview 3.2.0. To verify the association
      between urban quality and HIV prevalence in pregnant women, Poisson regression
      was used. RESULTS: A total of 137 HIV-positive women and 14 children infected by
      vertical transmission was reported. Seven children matched to HIV-positive
      mothers without notification in the period analyzed. HIV prevalence among
      pregnant women in the period was 0.44%, and the vertical transmission rate was
      9.7%. CONCLUSIONS: The prevalence of HIV infection among pregnant women and
      vertical transmission were associated with the urban quality of residential
      neighborhood. Neighborhoods with lower urban quality should be prioritized in
      actions to reduce vertical transmission.

PMID- 21739081
TI  - 37 years of scientific activity in a Biochemistry Department in Brazil: patterns
      of growth and factors leading to increased productivity.
AB  - Scientific activity in Brazil has experienced an accelerated growth in the past
      decades, with an increase in productivity that greatly surpasses the
      international average. This growth has occurred mostly at the expense of centers
      of excellence in public universities, which account for the vast majority of the
      country's scientific output. The aim of this study was to evaluate the production
      of the Department of Biochemistry of a large public university in southern Brazil
      (Universidade Federal do Rio Grande do Sul), as well as to identify internal and
      external policies that have influenced this growing production profile. We have
      performed a historical analysis of the scientific output of this Department of
      Biochemistry, which accounts for a considerable share of the indexed scientific
      production at this university. By focusing on the temporal course of its growth
      and drawing correlations between scientific output and important events in the
      history of the Department of Biochemistry and of the Brazilian science policies,
      we concluded that internal factors (as the creation of a postgraduation program,
      collaboration among researchers, experienced abroad researchers, qualification of
      faculty members) and external factors (as investments in the postgraduate
      education, the establishment of national scientific policies, such as financial
      stimuli for productive researchers and evaluation systems) influence scientific
      productivity in Brazil.

PMID- 21739082
TI  - Selection of phytotoxin producing rhizobacteria.
AB  - In order to select phytotoxin producing rhizobacteria to control weed plants,
      twenty five bacterial strains previously isolated from the rhizospheres of
      various plants were grown in a liquid medium and, after cell removal by
      centrifugation, the liquid phases were freeze-dried and the products were
      extracted with ethyl acetate/methanol. The extracts were concentrated to dryness
      under vacuum and dissolved in water and sucrose solution to be submitted to in
      vitro assays of lettuce (Lactuca sativa L.) seed germination and wheat (Triticum
      aestivum L.) coleoptile growth. Although most samples affected coleoptile growth,
      only those from four strains reduced lettuce seed germination. Two strains of
      Bacillus cereus, one strain of B. pumilus and one of Stenotrophoonas altophilia
      were the most promising microorganisms for producing phytotoxin and,
      consequently, for the development of new weed control products.

PMID- 21739083
TI  - Chagas disease in prehistory.
AB  - The classical hypothesis proposes that Chagas disease has been originated in the
      Andean region among prehistoric people when they started domesticating animals,
      changing to sedentary habits, and adopting agriculture. These changes in their
      way of life happened nearly 6,000 years ago. However, paleoparasitological data
      based on molecular tools showed that Trypanosoma cruzi infection and Chagas
      disease were commonly found both in South and North American prehistoric
      populations long before that time, suggesting that Chagas disease may be as old
      as the human presence in the American continent. The study of the origin and
      dispersion of Trypanosoma cruzi infection among prehistoric human populations may
      help in the comprehension of the clinical and epidemiological questions on Chagas
      disease that still remain unanswered.

PMID- 21739084
TI  - Karyotype analysis, DNA content and molecular screening in Lippia alba
      (Verbenaceae).
AB  - Cytogenetic analyses, of pollen viability, nuclear DNA content and RAPD markers
      were employed to study three chemotypes of Lippia alba (Mill.) (Verbenaceae) in
      order to understand the genetic variation among them. Different ploidy levels and
      mixoploid individuals were observed. This work comprises the first report of
      different chromosome numbers (cytotypes) in L. alba. The chromosome numbers of
      La2-carvone and La3-linalool chemotypes suggested that they are polyploids. Flow
      cytometric analysis showed an increase of nuclear DNA content that was not
      directly proportional to ploidy level variation. A cluster analysis based on RAPD
      markers revealed that La3-linalool shares genetic markers with La1-citral and La2
      carvone. The analysis showed that the majority of genetic variation of La3
      linalool could be a consequence of ixoploidy. ur data indicates that sexual
      reproduction aong those three chemotypes is unlikely and suggests the beginning
      of reproductive isolation. The results demonstrated that chromosome analysis,
      nuclear DNA content estimation and RAPD markers constitute excellent tools for
      detecting genetic variation among L. alba chemotypes.

PMID- 21739086
TI  - A comparison of models of the isometric force of locust skeletal muscle in
      response to pulse train inputs.
AB  - Muscle models are an important tool in the development of new rehabilitation and
      diagnostic techniques. Many models have been proposed in the past, but little
      work has been done on comparing the performance of models. In this paper, seven
      models that describe the isometric force response to pulse train inputs are
      investigated. Five of the models are from the literature while two new models are
      also presented. Models are compared in terms of their ability to fit to isometric
      force data, using Akaike's and Bayesian information criteria and by examining the
      ability of each model to describe the underlying behaviour in response to
      individual pulses. Experimental data were collected by stimulating the locust
      extensor tibia muscle and measuring the force generated at the tibia. Parameters
      in each model were estimated by minimising the error between the modelled and
      actual force response for a set of training data. A separate set of test data,
      which included physiological kick-type data, was used to assess the models. It
      was found that a linear model performed the worst whereas a new model was found
      to perform the best. The parameter sensitivity of this new model was investigated
      using a one-at-a-time approach, and it found that the force response is not
      particularly sensitive to changes in any parameter.

PMID- 21739087
TI  - An insight on multiscale tendon modeling in muscle-tendon integrated behavior.
AB  - This paper aims to highlight the need for a refined tendon model to reproduce the
      main mechanical features of the integrated muscle-tendon unit (MTU). Elastic
      nonlinearities of the tendon, both at the nano and microscale, are modeled by a
      multiscale approach, accounting for the hierarchical arrangement (from molecules
      up to the fibers) of the collagen structures within the tissue. This model
      accounts also for the variation of tendon stiffness due to physical activity.
      Since the proposed tendon model is based on tissue-structured histology, the
      training-driven adaptation laws are directly formulated starting from
      histological evidences. Such a tendon description is integrated into a
      viscoelastic Hill-type model of the whole MTU. A fixed-end contraction test is
      numerically simulated, and results based on both linear and nonlinear tendon
      elastic model are compared. Sound and effective time-histories of muscle
      contractile force and fiber length are obtained only accounting for tendon
      elastic nonlinearities, which allow to quantitatively recover some experimental
      data. Finally, proposed numerical results give clear indications toward a
      rational explanation of the influence of tendon remodeling induced by physical
      activity on muscular contractile force.

PMID- 21739088
TI  - A constrained von Mises distribution to describe fiber organization in thin soft
      tissues.
AB  - The semi-circular von Mises distribution is widely used to describe the unimodal
      planar organization of fibers in thin soft tissues. However, it cannot accurately
      describe the isotropic subpopulation of fibers present in such tissues, and
      therefore an improved mathematical description is needed. We present a modified
      distribution, formed as a weighted mixture of the semi-circular uniform
      distribution and the semi-circular von Mises distribution. It is described by
      three parameters: beta, which weights the contribution from each mixture
      component; k, the fiber concentration factor; and theta ( p ), the preferred
      fiber orientation. This distribution was used to fit data obtained by small-angle
      light scattering experiments from various thin soft tissues. Initial use showed
      that satisfactory fits of fiber distributions could be obtained (error generally
      < 1%), but at the cost of non-physically meaningful values of k and beta. To
      address this issue, an empirical constraint between the parameters k and beta was
      introduced, resulting in a constrained 2-parameter fiber distribution. Compared
      to the 3-parameter distribution, the constrained 2-parameter distribution fits
      experimental data well (error generally < 2%) and had the advantage of producing
      physically meaningful parameter values. In addition, the constrained 2-parameter
      approach was more robust to experimental noise. The constrained 2-parameter fiber
      distribution can replace the semi-circular von Mises distribution to describe
      unimodal planar organization of fibers in thin soft tissues. Inclusion of such a
      function in constitutive models for finite element simulations should provide
      better quantitative estimates of soft tissue biomechanics under normal and
      pathological conditions.

PMID- 21739089
TI  - Matrix extracellular phosphoglycoprotein is expressed in causative tumors of
      oncogenic osteomalacia.
AB  - Oncogenic osteomalacia (OOM), or tumor-induced osteomalacia, is a rare disease
      characterized by renal phosphate wasting and osteomalacia. It arises due to the
      secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Matrix
      extracellular phosphoglycoprotein (MEPE) is predominantly expressed in
      odontoblasts, osteoblasts, and osteocytes. Although the presence of MEPE mRNA has
      been reported in some OOM tumors, little is known about the prevalence of MEPE
      expression in OOM tumors. In this study, the expression of MEPE and FGF-23 in OOM
      tumors was investigated at the transcriptional and translational levels. Eleven
      causative OOM tumors were analyzed by quantitative real-time reverse
      transcription-polymerase chain reaction and immunohistochemistry for MEPE and FGF
      23 expression. Hemangiopericytomas and giant cell tumors, pathological diagnoses
      that are common in cases of OOM, were obtained from non-osteomalacic patients and
      analyzed as controls. The gene expression level of FGF23 and MEPE in OOM tumors
      was 10(4)- and 10(5)-times higher, respectively, than in non-OOM tumors.
      Immunohistochemical staining revealed that FGF-23 protein was expressed in all
      OOM tumors, and MEPE was expressed in 10 out of 11 OOM tumors. Thus, MEPE
      expression was common in OOM tumors, similar to FGF-23. These results indicate
      that, in addition to the hypophosphatemic effects of FGF-23, MEPE or the MEPE
      derived acidic serine aspartate-rich MEPE-associated motif peptide may contribute
      to decreased bone mineralization in OOM patients.

PMID- 21739090
TI  - Role of sphenopalatine ganglion block for postoperative analgesia after
      functional endoscopic sinus surgery.
AB  - The aim of this study was to evaluate the analgesic efficacy of sphenopalatine
      ganglion block performed under general anesthesia in patients undergoing
      functional endoscopic sinus surgery (FESS) with operative blood loss and
      postoperative complications (headache, visual disturbances, nausea, vomiting,
      sore throat, swallow difficulty). Forty-five consenting patients were randomized
      to receive bilateral sphenopalatine ganglion block with saline (Group S, n = 15),
      bupivacaine 0.5% (Group B, n = 15), or levobupivacaine 0.5% (Group L, n = 15)
      immediately following induction of general anesthesia. Esmolol was given during
      the intraoperative period for a 20% increase in arterial mean pressure or heart
      rate. Postoperative pain scores were checked on arrival at the postanesthesia
      care unit, 2, 6, and 24 h after surgery and diclofenac was administered
      intramuscularly for pain score >= 4. A statistically significant reduction was
      present in postoperative Visual Analog Scale scores between Group S and the block
      Groups B and L (p < 0.05). In Group L and B, fewer patients required additional
      analgesics in the postoperative 24 h (p < 0.0001). The comparison of
      postoperative complications was not statistically significant among the groups (p
      > 0.05). Sphenopalatine ganglion block with bupivacaine or levobupivacaine
      improved postoperative analgesia associated with better surgeon and patient
      satisfaction after FESS.

PMID- 21739091
TI  - The influence of various factors on the performance of repetition tests in adults
      with cochlear implants.
AB  - A variety of internal and external factors influence speech perception
      performance following cochlear implantation (CI) in adult deaf patients. The aim
      of this study was to evaluate the speech perception performance during repetition
      testing according to various factors and to identify the predictive factors
      associated with postoperative speech perception. The performances on speech
      perception under audio-only conditions were examined over time in 61 adult
      patients with CI. Mono- and bi-syllable and sentence repetition testing, using
      both the Korean version of the Central Institute for the Deaf (K-CID) and the K
      Western Aphasia Battery test (K-WAB), were performed preoperatively and at 3, 6
      and 12 months postoperatively. To elucidate the effect that the etiology of
      deafness has on postoperative outcome, patients were divided into the following
      four groups: Prelingual hearing loss (HL) (n = 9), Meningitis (n = 6),
      Progressive HL (n = 31) and Sudden HL groups (n = 15). Moreover, the duration of
      HL and deafness was defined as follows: (1) "age of deafness onset: AoD", (2)
      "number of years between the onset of profound deafness and CI: DoD" and (3)
      "percentage of the patient's life with moderate-to-profound hearing loss before
      CI: PoL". DoD and PoL were significantly different between the four groups.
      Although AoD appeared to be associated with performance on the sentence
      repetition test before standardizing for education level and age (P = 0.015),
      there was no association after adjusting for these factors (P = 0.719). Only PoL
      showed a good correlation with performance on repetition testing after CI after
      adjusting for AoD and DoD. However, DoD was associated with speech perception
      performance on the sentence repetition test only. In addition, speech perception
      performance results in the Progressive and Sudden HL groups were improved over
      the Prelingual HL and Meningitis groups. The Meningitis group showed the poorest
      speech perception performance among postlingually deaf adults. Consideration of
      age, education level, etiology and overall time with hearing loss may be
      necessary for predicting speech perception outcomes in CI recipients.

PMID- 21739092
TI  - Chemoradiation for advanced hypopharyngeal carcinoma: a retrospective study on
      efficacy, morbidity and quality of life.
AB  - Chemoradiation (CRT) is a valuable treatment option for advanced hypopharyngeal
      squamous cell cancer (HSCC). However, long-term toxicity and quality of life
      (QOL) is scarcely reported. Therefore, efficacy, acute and long-term toxic
      effects, and long-term QOL of CRT for advanced HSCC were evaluated,using
      retrospective study and post-treatment quality of life questionnaires. in a
      tertiary hospital setting. Analysis was performed of 73 patients that had been
      treated with CRT. Toxicity was rated using the CTCAE score list. QOL
      questionnaires EORTC QLQ-C30, QLQ-H&N35, and VHI were analyzed. The most common
      acute toxic effects were dysphagia and mucositis. Dysphagia and xerostomia
      remained problematic during long-term follow-up. After 3 years, the disease
      specific survival was 41%, local disease control was 71%, and regional disease
      control was 97%. The results indicated that CRT for advanced HSCC is associated
      with high locoregional control and disease-specific survival. However,
      significant acute and long-term toxic effects occur, and organ preservation
      appears not necessarily equivalent to preservation of function and better QOL.

PMID- 21739093
TI  - Development and validity of the DyNaChron questionnaire for chronic nasal
      dysfunction.
AB  - Nasal symptoms are the main elements that lead to a therapeutic decision and
      allow for evaluating treatment effects or natural evolution. Despite availability
      of several questionnaires with good measurement qualities, no systematic
      assessment takes into account the specific physical and psychosocial consequences
      of each of the six main nasal symptoms, independently of the disease. We proposed
      to measure these symptoms with the use of a self-reporting questionnaire and to
      test the validity of the questionnaire in a large representative sample of
      patients attending outpatient rhinologic clinics. The study was conducted in two
      parts: (1) expert-based development and testing of the face validity of a
      questionnaire in French; and (2) validity testing, including construct validity
      by factor analysis, reproducibility by intraclass correlation coefficient (ICC)
      and Bland and Altman plots, and sensitivity to change by standardized response
      means, on a large sample of patients in a prospective multicenter study.
      DyNaChron, a questionnaire with 78 items divided into six domains and exploring
      both the physical and psychosocial repercussions of CND, was developed. In total,
      759 patients completed the questionnaire at a first visit to a clinic, and 539
      again 19.5 days later, on average. The questionnaire structure was confirmed to
      be composed of six domains (6 factors explaining 68.7% of the variance), with two
      dimensions in each domain. The questionnaire's convergent validity was confirmed;
      the Cronbach alpha coefficient for domains was high (0.93-0.96), the ICC ranged
      from 0.8 to 0.92, and the questionnaire's sensitivity to change was greater for
      patients with improved health status than for those with worsened status.
      DyNaChron is a well-structured questionnaire with a high degree of internal
      consistency and all properties needed to be used in research. It should now be
      compared with other questionnaires and objective measures to assess whether or
      not DyNaChron better measures disease severity and its changes. Further work will
      involve shortening the instrument for use in clinical practice and create a
      "patient symptomatology score".

PMID- 21739094
TI  - Pediatric BAHA in Italy: the "Bambino Gesu" Children's Hospital's experience.
AB  - The "Bambino Gesu" Children's Hospital offers the largest Italian cohort of
      children using a BAHA. This paper retrospectively reviews the center's experience
      with pediatric BAHA from its start in 1995 to December 2009, especially focusing
      on most debated issues, all the way from candidate selection to functional
      outcome and complications. A total of 47 children (21 females and 26 males) were
      implanted. From 1995 to 2000, a two-stage procedure was adopted in 100% (n = 22)
      cases. From 2001 onwards, one-stage surgery was chosen for 10 patients. Implant
      loss occurred in two patients (4.2%) after a two-stage surgery. Overall, the
      local complication rate was not different in the one-stage and in the two-stage
      group. The functional gain was significantly better with BAHA than conventional
      bone-conduction hearing aids and there was no significant difference in terms of
      functional outcome between the seven patients receiving a BAHA at an age younger
      than 5 years and the rest. The study results suggest that children presenting an
      indication to auditory rehabilitation with BAHA should be referred to specialized
      tertiary care centers. Only in such settings, a complete, multidisciplinary
      approach to associated comorbidities and syndromes is possible, and implantation
      of children at an age younger than five and one-stage surgery can be conducted
      safely and effectively.

PMID- 21739095
TI  - Semicircular canal dehiscence in HR multislice computed tomography: distribution,
      frequency, and clinical relevance.
AB  - The literature about bony defects in the semicircular canal system is highly
      inconsistent. Therefore, we analyzed a series of 700 high-resolution multislice
      CT examinations of the temporal bone for semicircular canal dehiscencies. An
      unselected group of ENT patients with different clinical symptoms and variable
      age was chosen. We found semicircular canal dehiscence in 9.6% of temporal bones,
      superior semicircular canal was affected mostly (8%), less common posterior
      semicircular canal (1.2%); only in 3 cases (0.4%), lateral semicircular canal
      showed dehiscence. In 60% of SSC dehiscence, we registered bilateral
      manifestation. The so-called "third mobile window" in semicircular canal
      dehiscence causes a great variety of clinical symptoms like vertigo, nystagmus,
      oscillopsies, hearing loss, tinnitus and autophonia. Comparison with anatomic
      studies shows that CT examination implies the risk of considerable
      overestimation; this fact emphasizes the important role of clinical and
      neurophysiological testing.

PMID- 21739096
TI  - Impact of radiotherapy on laryngeal intrinsic muscles.
AB  - Ionizing radiation as a cancer therapy is associated with a variety of
      undesirable side effects. Consequently, radiotherapy can negatively affect
      neuromuscular function. Clinical observations have identified problems with
      swallowing and voice function. Our study aims to evaluate the impact of
      radiotherapy on laryngeal soft tissues using image analysis to quantify its
      effect on the structure of the vocalis and thyroarytenoid muscles. Case control
      study, retrospective analysis. We collected total laryngectomy specimens from six
      patients with persistent or recurrent cancer who had received preoperative
      radiotherapy (60-66 Gy). The control group consisted of total laryngectomy
      specimens from six patients who underwent surgery as primary treatment. Sampling
      of the specimens only included non-cancerous laryngeal tissue. Laryngeal
      histological slices were evaluated using digital morphometric analysis system.
      Percentage of fibrosis and density of muscle fibers within the thyroarytenoid
      muscle were evaluated in both groups. We found no significant quantitative
      differences in muscle fibrosis (7.92% vs. 7.52%, P > 0.1). Changes were rather
      qualitative and included changes in the organization of the muscular fibers. A
      significant reduction in muscle fibers, however, was observed in the samples from
      irradiated larynges (66.45% vs. 42.03%, P < 0.01). Our analysis suggests that
      radiotherapy is responsible for a significant reduction in muscle fibers in the
      thyroarytenoid muscle and that these changes occur during treatment or relatively
      early after its completion. Loss of muscle mass after irradiation correlates with
      clinical observations of muscle weakness and decreased function in patients who
      undergo radiotherapy.

PMID- 21739097
TI  - A decade of laryngeal dysplasia in Paisley, Scotland.
AB  - Laryngeal dysplasia is a known premalignant condition. A recent consensus
      statement by otorhinolaryngologists and pathologists on the diagnosis and
      management of laryngeal dysplasia Mehanna et al. (Clin Otol 35:170-176, 2010)
      identified a need for retrospective data on epidemiological aspects of laryngeal
      dysplasia as well as responses to treatment. A retrospective search was made on
      the hospital pathology database for cases of laryngeal dysplasia. Searches were
      made under "Larynx", "Dysplasia", "Carcinoma in situ" and "Vocal Cord". The
      search dates were between 1998 to the present day. The returned records were
      checked with the pathology reports and the case notes of these patients requested
      for analysis. A proforma was completed for each patient with laryngeal dysplasia.
      These patients were then anonymised, entered into a spreadsheet and analysed. The
      initial search returned 937 patients. Of these patients, 505 (54%) had benign
      laryngeal pathology, 131 (14%) had laryngeal dysplasia and 301 (32%) had invasive
      cancer on biopsy. Patients who developed malignancy within 3 months of being
      diagnosed with laryngeal dysplasia were excluded. This left 110 patients for
      analysis. Of the dysplastic patients, 40 (36%) had mild dysplasia, 31 (28%) had
      moderate dysplasia and 39 (35%) had severe dysplasia/carcinoma in situ; 70% were
      male. The median age was 63 (min 21, max 90, ave 62.5); 74 (67%) were smokers or
      ex-smokers. Progression of dysplasia was seen in 7 (6%) patients. Malignant
      transformation was seen in 18 (16%) patients. The average time for malignant
      change was 43 months (min 4 months, max 192 months and median 15.5 months; 73
      (66%) patients were treated by microlaryngeal resection, 2 (2%) were treated by
      vocal cord stripping, 28 (25%) were treated by endolaser therapy, and 1 (1%)
      patient was treated by using the microdebrider skimming blade and 6 (5%) were
      treated by radiotherapy. Cure of dysplasia or downgrading of severity in these
      treatment subgroups was 62 (85%), 2 (100%), 24 (86%), 1 (100%) and 4 (66%),
      respectively. Our study reiterates that laryngeal dysplasia carries a significant
      risk of developing malignancy. Management of this condition varies widely.
      Endolaser resection is becoming more frequently employed in the UK. Our study is
      biased heavily towards cold steel dissection. Although there is increasing
      practice in the UK to promote early discharge, we feel it may be safer to keep
      patients under surveillance for longer periods. Despite this, all patients who
      returned after discharge or failing to attend with invasive cancer did so with
      new symptoms.

PMID- 21739098
TI  - Relationship between bacterial biofilm and clinical features of patients with
      chronic rhinosinusitis.
AB  - The purpose of this study was to investigate the incidence of bacterial biofilm
      (BBF) in patients with chronic rhinosinusitis (CRS) using confocal scanning laser
      microscopy (CSLM), and to assess the relationship between BBF and clinical
      features of CRS. This was a prospective observational study of the sinus mucosa
      of 27 CRS patients and 10 controls undergoing endoscopic sinus surgery (ESS).
      Clinical information was recorded preoperatively and sinus mucosal specimens were
      collected intraoperatively. We determined the existence of BBF with BacLight/CSLM
      detection, and proposed a BBF scoring system based on its morphologic features.
      Clinical parameters, including symptom score, endoscopy score, CT score and
      symptom duration, were compared between CRS patients with and without BBF, and
      among CRS patients with different BBF score. BBF was found in 16/27 (59.26%) CRS
      patients and none in 10 controls. SNOT-20 symptom score and individual symptoms
      including need to blow nose, cough and postnasal discharge were significantly
      more severe in CRS patients with BBF than those without. BBF score was better
      correlated than BBF existence with SNOT-20 score (r = 0.811, P < 0.001 vs. r =
      0.604, P = 0.001), and correlated with both endoscopy score (r = 0.490, P =
      0.009) and symptom duration (r = 0.487, P = 0.010), neither was correlated with
      BBF (P = 0.824; P = 0.263). BBF score is likely to guide anti-BBF therapy in CRS
      patients.

PMID- 21739099
TI  - Dilute vinegar therapy for the management of spontaneous external auditory canal
      cholesteatoma.
AB  - The purpose of this study is to evaluate the efficiency of conservative dilute
      vinegar therapy in the management of spontaneous external auditory canal
      cholesteatoma (EACC). From 2000 to 2007, 19 patients presented to our clinic with
      spontaneous EACC. EACC was divided into four grades based on the temporal bone
      computed tomography: grade I with flattening of bony external canal, grade II
      with partial destruction of inferior bony canal, grade III with total destruction
      of inferior bony canal and grade IV with bony destruction into the middle ear and
      mastoid cavity. Clinical findings and treatment results were recorded.
      Microscopic local cleansing and dilute vinegar therapy was conducted in the ears
      with grades I, II and III. Combined mastoid surgery and dilute vinegar therapy
      was conducted in four ears with stage IV. There were no recurrences after average
      of 31 months follow-up. Spontaneous EACC can be effectively controlled with
      dilute vinegar therapy after microscopic local cleansing. However, surgery must
      be considered in the cases which have involved the mastoid and middle ear. Dilute
      vinegar therapy in combination with microscopic local cleansing was effective in
      the management of spontaneous EACC. Dilute vinegar therapy is an easy, cost
      effective, and home-based cleansing method to prevent EACC and promotes healing.
      However, long-term follow-up may reveal frequent recurrence of cholesteatoma
      debris and involvement of middle ear or mastoid cavity, and then meticulous
      debridement with skin graft or surgical intervention should be considered.

PMID- 21739100
TI  - Cricothyroid approximation for voice and swallowing rehabilitation of high vagal
      paralysis secondary to skull base neoplasms.
AB  - This study documents the speech and swallowing outcomes of isolated ipsilateral
      cricothyroid approximation (aka tensioning thyroplasty; Type IV thyroplasty) for
      the treatment of high vagal paralysis (combined superior laryngeal nerve and
      recurrent laryngeal nerve paralysis). This is a pilot study of five cases with
      high vagal paralysis consequent to skull base neoplasms. Unilateral cricothyroid
      tensioning sutures were used. In all cases, vocal fold tensioning and vertical
      realignment of lax vocal folds were achieved. A partial, but acceptable
      medialization of vocal cord position was achieved. In all cases, aspiration was
      minimized and normal swallow function was restored by 6 weeks. The voice outcome
      was excellent in four cases and acceptable in one. Cricothyroid approximation
      restores vocal fold tension; in addition, it restores vertical vocal fold
      position and partially restores horizontal vocal fold position. Good voice and
      swallowing outcomes have been achieved. The procedure is quick, safe, and
      convenient when combined with a skull-base excision procedure. Further evaluation
      is merited.

PMID- 21739101
TI  - The effect of delays in treatment for breast cancer metastasis on survival.
AB  - It is generally accepted that delay in receiving treatment for breast cancer
      results in adverse outcomes. The purpose of this study was to evaluate the impact
      of delay in treatment after the diagnosis of metastatic disease on survival
      measured from metastatic breast cancer diagnosis and from first treatment while
      controlling for immortal time effect among patients with metastatic breast
      cancer. A total of 553 patients with breast cancer metastasis diagnosis from one
      large urban practice have been followed between January 1, 1999 and June 30,
      2008. Prognostic factors and outcomes of these patients were analyzed using log
      rank test and Cox regression model. Backward stepwise selection of covariates was
      conducted to assess the association of treatment delay with survival. The median
      survival was 40 months (range 1-114 months), with 265 (47.9%) women alive and 288
      (52.1%) having died at the end of the follow-up period. Treatment delays of more
      than 12 weeks had impact on poor survival from first treatment than the delays of
      4-12 weeks with borderline significance level (HR 1.76, 95% CI 0.99-3.13, P =
      0.056) in multivariate analysis, adjusted by BMI, history of hypertension, ER/PR
      status, HER2 status, number of metastatic sites, and liver metastasis. Moreover,
      the interval of 12-24 weeks, compared to the interval of 4-12 weeks was
      associated with greater risk of death from first treatment (HR 2.39, 95% CI 1.19
      4.77, P = 0.014). The treatment delay interval of >12 weeks was not related with
      survival since metastatic breast cancer diagnosis, compared to the 4-12 weeks of
      treatment delays. This study demonstrated that delays of over 12 weeks in
      receiving treatment for metastatic breast cancer were related to adverse survival
      outcomes measured from initiation of first treatment. The findings of this study
      support targeted efforts to ensure prompt treatment initiation in patients
      diagnosed with metastatic breast cancer.

PMID- 21739103
TI  - Comparison between loose fragment chondrocytes and condyle fibrochondrocytes in
      cellular proliferation and redifferentiation.
AB  - BACKGROUND: Loose fragments in spontaneous osteonecrosis of the knee (SONK) are
      usually removed by surgical treatment. However, the healing potential of
      osteonecrotic loose fragments and their clinical availability, for example as a
      cell source for cartilage repair and tissue engineering, have not been
      investigated. The objective of this study was to evaluate the cellular
      proliferation and redifferentiation ability of loose fragment chondrocytes for
      the treatment of SONK. METHODS: Cells were obtained from the remaining cartilage
      of chondral loose fragments or fibrocartilaginous tissue under the affected
      femoral condyle in SONK. The proliferation activity of loose fragment-derived
      chondrocytes and condyle-derived fibrochondrocytes was evaluated. In-vitro
      differentiation ability was assessed by PCR and histological analysis. RESULTS:
      The deposition of proteoglycans and type II collagen were maintained in loose
      fragments. However, loose fragment-derived chondrocytes had lower proliferating
      activity than condyle-derived fibrochondrocytes. Chondrogenic redifferentiation
      ability was lower in loose fragment chondrocytes than in condyle
      fibrochondrocytes. Differentiation towards adipogenic and osteogenic lineages was
      not observed in loose fragment chondrocytes. On the other hand, lipid vacuoles
      were detected in fibrochondrocytes after adipogenic treatment. CONCLUSIONS: This
      study demonstrated that loose fragment-derived chondrocytes in SONK had lower
      potential than fibrochondrocytes in cellular proliferation and redifferentiation.
      Our experimental results suggest that osteonecrotic loose fragments might have
      restricted cellular properties in the healing of SONK-related osteochondral
      defects.

PMID- 21739104
TI  - Combination of texture analysis and bone mineral density improves the prediction
      of fracture load in human femurs.
AB  - Twenty-one excised femurs were studied using (1) a high-resolution digital X-ray
      device to estimate three textural parameters, (2) dual-energy X-ray
      absorptiometry (DXA) to measure bone mineral density (BMD), and (3) mechanical
      tests to failure. Textural parameters significantly correlated with BMD (p <
      0.05) and bone strength (p < 0.05). Combining texture parameters and BMD
      significantly improved the fracture load prediction from adjusted r(2) = 0.74 to
      adjusted r(2) =0.82 (p < 0.05). INTRODUCTION: The purpose of this study is to
      determine if the combination of bone texture parameters using a new high
      resolution X-ray device and BMD measurement by DXA provided a better prediction
      of femoral failure load than BMD evaluation alone. METHODS: The proximal ends of
      21 excised femurs were studied using (1) a high-resolution digital X-ray device
      (BMA, D3A Medical Systems) to estimate three textural parameters: fractal
      parameter Hmean, co-occurrence, and run-length matrices, (2) DXA to measure BMD,
      and (3) mechanical tests to failure in a side-impact configuration. Regions of
      interest in the femoral neck, intertrochanteric region, and greater trochanter
      were selected for DXA and bone texture analysis. Every specimen was scanned twice
      with repositioning before mechanical testing to assess reproducibility using
      intraclass correlation coefficient (ICC) with 95% confidence interval. The
      prediction of femoral failure load was evaluated using multiple regression
      analysis. RESULTS: Thirteen femoral neck and 8 intertrochanteric fractures were
      observed with a mean failure load of 2,612 N (SD, 1,382 N). Fractal parameter
      Hmean, co-occurrence, and run-length matrices each significantly correlated with
      site-matched BMD (p < 0.05) and bone strength (p < 0.05). The ICC of the textural
      parameters varied between 0.65 and 0.90. Combining bone texture parameters and
      BMD significantly improved the fracture load prediction from adjusted r(2) =0.74
      to adjusted r(2) = 0.82 (p < 0.05). CONCLUSION: In these excised femurs, the
      combination of bone texture parameters with BMD demonstrated a better performance
      in the failure load prediction than that of BMD alone.

PMID- 21739105
TI  - Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral
      density and decreased bone turnover, but high fracture rate persists.
AB  - Bisphosphonates can increase bone mineral density (BMD) in children with
      osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate
      increased BMD at lumbar spine (but not total hip) and decreased bone turnover.
      However, the fracture rate in these patients remained high. INTRODUCTION:
      Intravenous bisphosphonates given to children with OI can increase BMD and reduce
      fracture incidence. Oral and/or intravenous bisphosphonates may have similar
      effects in adults with OI. We completed an observational study of the effect of
      risedronate in adults with OI type I. METHODS: Thirty-two adults (mean age, 39
      years) with OI type I were treated with risedronate (total dose, 35 mg weekly)
      for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and
      total hip (TH). Secondary outcome measures were fracture incidence, bone pain,
      and change in bone turnover markers (serum procollagen type I aminopropeptide
      (P1NP) and bone ALP). A meta-analysis of published studies of oral
      bisphosphonates in adults and children with OI was performed. RESULTS: Twenty
      seven participants (ten males and seventeen females) completed the study. BMD
      increased at LS by 3.9% (0.815 vs. 0.846 g/cm(2), p = 0.007; mean Z-score, -1.93
      vs. -1.58, p = 0.002), with no significant change at TH. P1NP fell by 37% (p =
      0.00041), with no significant change in bone ALP (p = 0.15). Bone pain did not
      change significantly (p = 0.6). Fracture incidence remained high, with 25
      clinical fractures and 10 major fractures in fourteen participants (0.18 major
      fractures per person per year), with historical data of 0.12 fractures per person
      per year. The meta-analysis did not demonstrate a significant difference in
      fracture incidence in patients with OI treated with oral bisphosphonates.
      CONCLUSIONS: Risedronate in adults with OI type I results in modest but
      significant increases in BMD at LS, and decreased bone turnover. However, this
      may be insufficient to make a clinically significant difference to fracture
      incidence.

PMID- 21739106
TI  - Synthesis and minimum inhibitory concentrations of SK-03-92 against
      Staphylococcus aureus and other gram-positive bacteria.
AB  - Staphylococcus aureus causes hundreds of thousands of infections and thousands of
      deaths per year in the United States. The emergence of methicillin-resistant S.
      aureus (MRSA), including community-associated methicillin-resistant S. aureus (CA
      MRSA), has added to the problem. As MRSA continue to evolve, they are becoming
      resistant to more classes of antibiotics. In the past 20 years, only three new
      antibiotics have been approved for human use (linezolid, daptomycin, and
      tigecycline), and resistance to these three drugs has already emerged. New
      antibiotics are needed, and we have developed a promising drug candidate that may
      be applicable to treating MRSA, among other gram-positive bacterial infections.
      We have identified a novel synthetic drug, coded SK-03-92, that shows broad in
      vitro efficacy against a variety of gram-positive bacterial strains that include
      a number of strains of S. aureus. Besides the activity against gram-positive
      bacteria, this new drug also exhibits activity against Mycobacterium strains.

PMID- 21739107
TI  - Juvenile myoclonic epilepsy presenting as a new daily persistent-like headache.
AB  - New daily persistent headache (NDPH) is a recognized subtype of chronic daily
      headache with a unique presentation of a daily headache from onset typically in
      individuals with minimal or no prior headache history. Various secondary mimics
      of NDPH have now been documented but at present there has been no association
      made between primary epilepsy syndromes and new daily persistent-like headaches.
      A case patient is presented who developed a daily continuous headache from onset
      who 3 months after headache initiation had her first generalized tonic-clonic
      seizure. Further investigation into her history and her specific EEG pattern
      suggested a diagnosis of juvenile myoclonic epilepsy (JME). Her NDPH and seizures
      ceased with epilepsy treatment. Clinically relevant was that the headache was the
      primary persistent clinical symptom of her JME before the onset of generalized
      tonic-clonic seizures. The current case report adds another possible secondary
      cause of new daily persistent-like headaches to the medical literature and
      suggests another association between primary epilepsy syndromes and distinct
      headache syndromes.

PMID- 21739108
TI  - Synthesis and secretion of gonadotropins including structure-function correlates.
AB  - The synthesis and secretion of the gonadotropic hormones involves coordination of
      signal transduction, gene expression, protein translation, post-translational
      folding and modification and finally secretion. The production of biologically
      active gonadotropin thus requires appropriately folded and glycosylated subunits
      that assemble to form the heterodimeric hormone. Here we overview recent
      literature on regulation of gonadotropin subunit gene expression and current
      understanding of the assembly and secretion of biologically active gonadotropic
      hormones. Finally, we discuss the therapeutic potential of understanding
      glycosylation function towards designing new forms of gonadotropins based on
      observations of physiologically relevant parameters such as age related
      glycosylation changes.

PMID- 21739109
TI  - Serum peptidome profiling in patients with gastric cancer.
AB  - To identify discriminating protein patterns in serum samples between gastric
      cancer patients (early and advanced stages) and healthy controls. We used
      magnetic bead-based separation followed by matrix-assisted laser desorption
      ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) to identify
      patients with gastric cancer. In total, serum samples from 62 gastric cancer
      patients (32 in the training set and 30 in the test set; 19 of which had early
      stage tumors and 43 of which had advanced-stage tumors) and 64 healthy controls
      (32 in the training set and 32 in the test set) were analyzed. The mass spectra,
      analyzed using ClinProTools software, distinguished between cancer patients and
      healthy individuals based on three different algorithm models. In the training
      set, patients with gastric cancer could be identified with a mean sensitivity of
      94.7% and a mean specificity of 99%. Similar results were obtained with the test
      set, showing 79.3% sensitivity and 86.5% specificity. Our study demonstrates the
      high sensitivity and specificity of screening serum protein patterns using MALDI
      TOF MS for the identification of patients with gastric cancer.

PMID- 21739110
TI  - Articular surface remodeling of the hip after periacetabular osteotomy.
AB  - PURPOSE: Periacetabular osteotomies are a family of surgical procedures used to
      treat hip dysplasia. In a periacetabular osteotomy, the operating surgeon aims to
      increase acetabular coverage of the femoral head. The surgical correction has
      mechanical goals of increasing the stability of the joint and to improving the
      pressure distribution across the acetabulum. Although it is known that bone will
      remodel under changing load at the microstructural level, it is unclear whether
      there is any gross remodeling of the acetabulum or the femoral head in response
      to the change in loading following a periacetabular osteotomy. This observational
      study aims to quantify the shape of operative and contralateral hip joint
      surfaces pre and postoperatively to determine whether there are gross
      morphological changes in the shape of any of the bony articular surfaces of the
      joint. METHODS: Preoperative and postoperative computed tomography (CT) scans
      were segmented as triangulated meshes. The bony articular surfaces of these
      meshes were then isolated. The vertices of these surfaces were fit to spheres and
      to general ellipsoids and, in the case of the acetabulum, examined in anatomical
      coordinate frames to look for changes between pre and postoperative
      segmentations. RESULTS: Spherical fit results were consistent preoperatively and
      postoperatively, with small changes in the radii of the spheres of best fit for
      both operative and nonoperative hips. Ellipsoid fitting showed variations between
      preoperative and postoperative scans in both eccentricity and orientation.
      CONCLUSIONS: Because there is no clear evidence of gross articular surface
      remodeling, periacetabular osteotomy for an adult should be planned with the
      expectation that the patient's existing articular structure will be preserved.

PMID- 21739111
TI  - Automatic segmentation of pulmonary blood vessels and nodules based on local
      intensity structure analysis and surface propagation in 3D chest CT images.
AB  - PURPOSE: Pulmonary nodules may indicate the early stage of lung cancer, and the
      progress of lung cancer causes associated changes in the shape and number of
      pulmonary blood vessels. The automatic segmentation of pulmonary nodules and
      blood vessels is desirable for chest computer-aided diagnosis (CAD) systems.
      Since pulmonary nodules and blood vessels are often attached to each other,
      conventional nodule detection methods usually produce many false positives (FPs)
      in the blood vessel regions, and blood vessel segmentation methods may
      incorrectly segment the nodules that are attached to the blood vessels. A method
      to simultaneously and separately segment the pulmonary nodules and blood vessels
      was developed and tested. METHOD: A line structure enhancement (LSE) filter and a
      blob-like structure enhancement (BSE) filter were used to augment initial
      selection of vessel regions and nodule candidates, respectively. A front surface
      propagation (FSP) procedure was employed for precise segmentation of blood
      vessels and nodules. By employing a speed function that becomes fast at the
      initial vessel regions and slow at the nodule candidates to propagate the front
      surface, the front surface can be propagated to cover the blood vessel region
      with suppressed nodules. Hence, the resultant region covered by the front surface
      indicates pulmonary blood vessels. The lung nodule regions were finally obtained
      by removing the nodule candidates that are covered by the front surface. RESULT:
      A test data set was assembled including 20 standard-dose chest CT images obtained
      from a local database and 20 low-dose chest CT images obtained from lung image
      database consortium (LIDC). The average extraction rate of the pulmonary blood
      vessels was about 93%. The average TP rate of nodule detection was 95% with 9.8
      FPs/case in standard-dose CT image, and 91.5% with 10.5 FPs/case in low-dose CT
      image, respectively. CONCLUSION: Pulmonary blood vessels and nodules segmentation
      method based on local intensity structure analysis and front surface propagation
      were developed. The method was shown to be feasible for nodule detection and
      vessel extraction in chest CAD.

PMID- 21739112
TI  - Combination of computer-aided detection algorithms for automatic lung nodule
      identification.
AB  - PURPOSE: The aim of this work is to evaluate the potential of combining different
      computer-aided detection (CADe) methods to increase the actual support for
      radiologists of automated systems in the identification of pulmonary nodules in
      CT scans. METHODS: The outputs of three different CADe systems developed by
      researchers of the Italian MAGIC-5 collaboration were combined. The systems are:
      the CAMCADe (based on a Channeler-Ant-Model which segments vessel tree and nodule
      candidates and a neural classifier), the RGVPCADe (a Region-Growing- Volume
      Plateau algorithm detects nodule candidates and a neural network reduces false
      positives); the VBNACADe (two dedicated procedures, based respectively on a 3D
      dot-enhancement algorithm and on intersections of pleura surface normals,
      identifies internal and juxtapleural nodules, and a Voxel-Based-Neural-Approach
      reduces false positives. A dedicated OsiriX plugin implemented with the Cocoa
      environments of MacOSX allows annotating nodules and visualizing singles and
      combined CADe findings. RESULTS: The combined CADe has been tested on thin slice
      (lower than 2 mm) CTs of the LIDC public research database and the results have
      been compared with those obtained by the single systems. The FROC (Free Receiver
      Operating Characteristic) curves show better results than the best of the single
      approaches. CONCLUSIONS: Has been demonstrated that the combination of different
      approaches offers better results than each single CADe system. A clinical
      validation of the combined CADe as second reader is being addressed by means of
      the dedicated OsiriX plugin.

PMID- 21739113
TI  - Negative argument for debate with V. O. Emery for J Neural Transmission :
      Alzheimer's disease: are we intervening too late? No we are not. Con.
AB  - Alzheimer's disease (AD) represents a major public health challenge. It is the
      most common cause of dementia, the worldwide prevalence of which will double
      every 20 years in the foreseeable future. It would be good if it were possible to
      treat AD early to diminish its impact, but current evidence does not support
      early intervention. Vitamin E was no more effective than placebo in a study of
      vitamin E and donepezil against placebo in mild cognitive impairment (MCI).
      Vitamin E is associated with a higher rate of haemorrhagic events than is
      placebo. Neither donepezil nor galantamine has been shown to be helpful in
      retarding progression from MCI to AD. Gingko biloba was ineffective in delaying
      the onset of AD in a large prospective trial involving over 6,000 participants.
      Gamma secretase inhibitors have not yet been shown to retard the progression of
      AD and they seem to have a high incidence of adverse effects, especially rashes.
      Antibody therapy has not yet been shown to be helpful in the treatment of
      established AD, let alone its prevention. Metalloproteinase modifiers such as
      PBT2 may be useful AD therapies, but current evidence gives no support to their
      immediate use in pre-symptomatic AD. No evidence can yet be adduced to support
      the use of antibody therapies in MCI or early AD. Thus, it is clear that the
      early treatment of AD cannot be justified as yet, no matter how desirable this
      goal may be. Treatment of established AD with cholinesterase inhibitors and
      memantine, coupled with referral of interested patients to evaluative drug
      trials, is the best we can do at present.

PMID- 21739114
TI  - Hip abductor muscle strength after total hip arthroplasty with short stems.
AB  - Excellent clinical results have been reported for total hip arthroplasty (THA)
      using a short stem. However, the range of variance in positioning of the stem has
      been reported to be wide. The authors hypothesized that the short stem position
      influences the femoral offset (FO) and hip abductor muscle strength (AMS) after
      surgery. The AMS was evaluated in 64 limbs in 32 patients who underwent
      unilateral THA using a short stem with a normal contralateral hip. The average
      time of AMS evaluation was 46.3 months postoperatively. The Harris Hip Score
      (HHS) was used for clinical evaluation. The ratio of the AMS on the reconstructed
      side to that on the contralateral side was calculated (strength ratio). The
      valgus angle (VA) of each stem and FO was measured on an anteroposterior hip
      radiograph. The FO ratio, as the normalized FO, was calculated. Linear regression
      analyses were performed to investigate the relationships among the VA, FO ratio
      and strength ratio. The average HHS improved from 57.7 points preoperatively to
      94.6 points postoperatively. The VA negatively correlated with the FO ratio (r = 
      0.511, P = 0.028). The strength ratio negatively correlated with the VA (r = 
      0.505, P = 0.032) and positively correlated with the FO ratio (r = 0.479, P =
      0.0056). The average postoperative HHS was generally satisfactory after THA using
      a short stem. A more valgus postoperative position of the short stem leads to
      reduced FO, which causes decreasing postoperative AMS after THA with a short
      stem.

PMID- 21739115
TI  - Relationship between human femorotibial joint configuration and the morphometry
      of the anterior cruciate ligament.
AB  - INTRODUCTION: Individual variations in the anatomy of the knee joint have been
      suggested to affect the ability to functionally compensate for ACL insufficiency
      or to put an individual at an increased risk of ACL injury. These variations
      include the posterior tibial slope, the concavity of the medial tibial plateau,
      the convexity of the lateral tibial plateau, and the configuration of the femoral
      condyles. METHOD: This anatomical study investigates if there is a correlation
      between the individual surface geometry of the femorotibial joint and the
      morphometry of the ACL. These data were assumed to provide evidence whether or
      not the functional stability of an ACL-insufficient knee may be derived from its
      radiographic surface geometry. Standardised measurement techniques were used to
      analyse the surface geometry of 68 human cadaver knees. Data were correlated with
      the cross-sectional area, the area of insertion and position of the footprint of
      the ACL and its functional bundles. RESULTS: Analysis revealed that there was a
      significant, but weak correlation between the femoral and tibial area of ACL
      insertion and the depth of the medial and lateral femoral condyle. No correlation
      was found between the surface geometry of the femorotibial joint and the cross
      sectional area of the ACL. The results of this anatomical study suggest that the
      relationship between the joint surfaces and the morphometry of the ACL primarily
      is a function of size of the knee joint. CONCLUSIONS: Based on our results, there
      is no evidence that the stability of the knee can be derived from its
      radiographic surface geometry.

PMID- 21739116
TI  - Cross-linked ultra-high-molecular weight polyethylene liner and ceramic femoral
      head in total hip arthroplasty: a prospective study at 5 years follow-up.
AB  - BACKGROUND: Recent data indicate that enhanced wear resistance can be obtained
      with new cross-linked ultra-high-molecular weight polyethylene (CL-UHMWPE)
      liners, in comparison with previous-generation liners. The current prospective,
      cohort study was undertaken to analyse whether the use of a new CL-UHMWPE
      (Rexpol) results in a lower wear rate than ultra-high-molecular weight
      polyethylene (UHMWPE) in a group of similar patients undergoing total hip
      arthroplasty (THA). This study provides the first clinical data with this
      particular CL-UHMWPE. METHODS: Between January 2001 and December 2001, patients
      underwent THA with biconical threaded cups and ceramic femoral heads using either
      a CL-UHMWPE liner (n = 50) or a regular UHMWPE liner (n = 57). At the time of the
      final 5-year evaluation, there were 48 patients available in the CL-UHMWPE and 54
      patients available in the UHMWPE group. RESULTS: After a mean 5.6 years follow
      up, there were no significant differences between the groups in Harris Hip Score
      outcomes. However, there was a 69.1% decrease in wear at 5 years for the CL
      UHMWPE group in comparison with the UHMWPE group (p < 0.01). CONCLUSION: The use
      of CL-UHMWPE significantly reduced the risk of polyethylene wear in patients
      undergoing THA with biconical threaded cups and ceramic femoral heads. Further
      follow-up is needed to determine how this will influence long-term outcomes.

PMID- 21739117
TI  - No evidence for association between a functional promoter variant of the
      Norepinephrine Transporter gene SLC6A2 and ADHD in a family-based sample.
AB  - Noradrenergic neurotransmission influences executive functions, attentional
      performance, and general alertness, involving neuronal networks affected in
      attention deficit/hyperactivity disorder (ADHD). The norepinephrine transporter
      facilitates the reuptake of norepinephrine and dopamine in the prefrontal cortex
      and represents the main target of atomoxetine, an effective drug in the treatment
      of ADHD. Due to its influence on catecholaminergic signaling, variants of the
      coding gene (SLC6A2) have been widely investigated in ADHD. Several previous
      studies report an association between single nucleotide polymorphisms located in
      SLC6A2 and ADHD; however, the findings are inconsistent. The variant A-3081T
      (rs28386840) has been shown to have major influence on the expression levels of
      SLC6A2 due to sequence alteration at a repressor binding site, with the T-allele
      being associated with ADHD. We tested this potential association of A-3081T in a
      German family-based ADHD sample of 235 children from 162 families, which has a
      power >99% based on the previously reported odds ratios. There was no evidence
      for an overtransmission of the risk allele T (transmission rate: 48.5%, P =
      0.55). We conclude that A-3081T is not a major risk variant in our ADHD sample,
      though SLC6A2 remains an interesting candidate gene in ADHD, especially for the
      inattentive subtype.

PMID- 21739118
TI  - The potential role of thioredoxin 1 and CD30 systems as multiple pathway targets
      and biomarkers in tumor therapy.
AB  - Our progress in understanding pathological disease mechanisms has led to the
      identification of biomarkers that have had a considerable impact on clinical
      practice. It is hoped that the move from generalized to stratified approaches,
      with the grouping of patients into clinical/therapeutic subgroups according to
      specific biomarkers, will lead to increasingly more effective clinical treatments
      in the near future. This success depends on the identification of biomarkers that
      reflect disease evolution and can be used to predict disease state and therapy
      response, or represent themselves a target for treatment. Biomarkers can be
      identified by studying relationships between serum, tissue, or tumor
      microenvironment parameters and clinical or therapeutic parameters at onset and
      during the progression of the disease, using systems biology. Given that multiple
      pathways, such as those responsible for redox and immune regulation, are
      deregulated or altered in tumors, the future of tumor therapy could lie in the
      simultaneous targeting of these pathways using extracellular and intracellular
      targets and biomarkers. With this aim in mind, we evaluated the role of
      thioredoxin 1, a key redox regulator, and CD30, a cell membrane receptor, in
      immune regulation. Our results lead us to suggest that the combined use of these
      biomarkers provides more detailed information concerning the multiple pathways
      affected in disease and hence the possibility of more effective treatment.

PMID- 21739119
TI  - Effect of trabectedin on the QT interval in patients with advanced solid tumor
      malignancies.
AB  - PURPOSE: The primary objective of this study was to access the potential effects
      of trabectedin on the QT/QTc interval in patients with locally advanced or
      metastatic solid tumors. METHODS: Patients (n = 75) who had received <=3 previous
      lines of chemotherapy and had either relapsed or had progressive disease were
      enrolled. Patients were administered 3-h intravenous infusions of placebo
      (saline) on day 1 and trabectedin (1.3 mg/m(2)) on day 2. Time-matched serial
      triplicate ECG recordings and pharmacokinetic blood samples were collected over
      24 h on both days. Heart rate corrected mean QT intervals and changes from
      predose baseline in QTc (DeltaQTc) were assessed. The difference in DeltaQTc
      between trabectedin and placebo was calculated at each time point
      (DeltaDeltaQTc). RESULTS: The upper limits of the 90% confidence interval for
      DeltaDeltaQTcF and DeltaDeltaQTcB at all time points were less than the
      prespecified noninferiority margin of 10 ms (<=6.65 ms). No patient had a QTc >
      500 ms or a time-matched increase from baseline in QTc > 60 ms at any time point.
      Regression analyses indicated DeltaDeltaQTc was poorly correlated with
      trabectedin concentration. No adverse events suggestive of proarrhythmic
      potential were reported. CONCLUSION: Trabectedin did not prolong the QTc
      interval. Safety and pharmacokinetic profiles of trabectedin were similar to that
      observed in other ovarian and breast cancer studies.

PMID- 21739120
TI  - Association of tumor-associated trypsin inhibitor (TATI) expression with
      molecular markers, pathologic features and clinical outcomes of urothelial
      carcinoma of the urinary bladder.
AB  - PURPOSES: To describe the differential tissue expression of tumor-associated
      trypsin inhibitor (TATI) in normal bladder urothelium, primary urothelial
      carcinoma of the bladder (UCB) and metastatic UCB and to assess the association
      of TATI expression with molecular markers commonly altered in UCB and clinical
      outcomes after radical cystectomy. METHODS: Slides from eight cystectomy patients
      without cancer, 191 radical cystectomy patients, 20 lymph nodes without
      metastasis and 40 lymph nodes with UCB were stained. Tissue expression of TATI,
      cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin and
      Cyclooxigenase-2 was measured in a tissue microarray. Cancer-specific and
      recurrence-free survival after radical cystectomy was recorded. RESULTS: TATI was
      expressed in 100% of patients without cancer, while 71% of radical cystectomy
      specimens and 90% of lymph node metastases exhibited decreased or no TATI
      expression. In radical cystectomy specimens, TATI expression decreased with
      advancing pathologic stage (P < 0.001) and lymphovascular invasion (P = 0.055).
      In univariate analyses, but not in multivariable Cox proportional hazard
      regression analyses, decreased TATI expression was associated with increased
      probability of tumor recurrence and cancer-specific mortality. Decreased TATI
      expression was correlated with altered expression of Cyclooxigenase-2 (P =
      0.005), p21 (P = 0.035) and Ki-67 (P = 0.004). CONCLUSIONS: We found that normal
      urothelium expresses TATI and that TATI expression decreases with advancing tumor
      stage. While there was no prognostic benefit to TATI when adjusted for standard
      clinicopathologic features, it seems to play an important biologic role in UCB
      pathogenesis and invasion. Its association with markers involved in the cell
      cycle, proliferation and inflammation serves as hypothesis for molecular
      interactions.

PMID- 21739121
TI  - The influence of age on bioavailable and free testosterone is independent of body
      mass index and glucose levels.
AB  - PURPOSE: To evaluate the influence of age on serum levels of total testosterone
      (TT), bioavailable testosterone (BT), free testosterone (FT), and sex-hormone
      binding globulin (SHBG), considering the presence of fasting blood glucose levels
      and body mass index (BMI) in a selected male population. METHODS: A total of 428
      men were analyzed. Anthropometry was taken from all, considering BMI as general
      obesity indicative variable. Fasting blood samples were drawn for determination
      of plasma glucose levels and serum levels of albumin, TT, and SHBG. The values of
      BT and FT were calculated from TT, SHBG, and albumin, by Vermeulen's equation.
      Statistical significance was set at P <= 0.05. RESULTS: Age was negatively
      correlated to BT (r = -0.301; P < 0.001) and FT (r = -0.273; P < 0.001), but not
      to TT levels (r = 0.002, P = 0.974). Age was positively correlated to SHBG (r =
      0.376; P < 0.001). Age was independently associated with the occurrence of high
      SHBG levels (OR = 1.07, 95%CI = 1.05-1.10, P < 0.001) and of low BT (OR = 1.04,
      95%CI = 1.02-1.07, P < 0.001) and FT levels (OR = 1.05, 95%CI = 1.03-1.08, P <
      0.001), but not with low levels of TT (P = 0.08). CONCLUSIONS: Age was
      significantly associated to high levels of SHBG and to low levels of BT and FT,
      without significant association to TT. This pattern was independent of BMI and
      glucose levels.

PMID- 21739122
TI  - Immunotherapy response evaluation with (18)F-FDG-PET in patients with advanced
      stage renal cell carcinoma.
AB  - BACKGROUND: CT imaging is widely used for response evaluation of immunotherapy in
      patients with advanced stage renal cell carcinoma (RCC). However, this kind of
      treatment may not immediately be cytoreductive, although the treatment is
      successful. This poses new demands on imaging modalities. Positron emission
      tomography (PET) using (18)F-fluorodeoxyglucose (FDG) proved to be useful in
      monitoring the effect of several antitumour treatments. We investigated the
      potential of FDG-PET for the evaluation of response to immunotherapy. METHODS: In
      seven patients with metastasized RCC, who were treated with either interferon
      alpha (IFN-alpha) monotherapy or a combination of IFN-alpha, interleukin-2 and 5
      fluorouracil, FDG-PET was performed prior and after 5 and 9 weeks of treatment.
      Quantitative changes of glucose metabolic rate (MRGlu) were compared with changes
      in tumour size on CT imaging using Response Evaluation Criteria in Solid Tumors
      (RECIST) and to survival and progression-free survival. RESULTS: No consistent
      changes in MRGlu were observed within different response groups. And no
      correlation with CT imaging, neither with survival or progression-free survival,
      was found. CONCLUSION: In contrast to the positive results reported on (chemo)
      therapy response evaluation with FDG-PET in different malignancies, this imaging
      modality appears not useful in response monitoring of immunotherapeutic
      modalities in RCC.

PMID- 21739124
TI  - Natural orifice (NOTES) transurethral sutureless radical prostatectomy with
      thulium laser support: first patient report.
AB  - INTRODUCTION: The aim of this descriptive study was to demonstrate the
      feasibility and safety of the first true transurethral sutureless radical
      prostatectomy for prostate cancer in humans using the NOTES technique. MATERIALS
      AND METHODS: A 77-year-old man with clinically localized bilateral prostate
      cancer (Gleason 3 + 4 = 7 in 80% of 12 biopsy cores) and a serum PSA level of 2.1
      ng/ml underwent our first natural orifice transurethral radical thulium laser
      prostatectomy within toto organ retrieval via sectio alta. The surgical procedure
      is described. RESULTS: The procedure was completed successfully. Overall
      operation time was 312 min; laser time was 46 min with 151 KJ. Postoperative
      hemoglobin was 9.4 g/dl, and the hematocrit was 28%. A cystogram on the 7th
      postoperative day showed no signs of extravasation and the transurethral catheter
      was removed, and a flexible cystoscopy on the 9th day demonstrated a sufficient
      arbitrarily sphincter closure against irrigation flow. CONCLUSION: The presented
      descriptive report demonstrates that natural orifice transurethral radical
      thulium laser prostatectomy for prostate cancer is feasible and safe. Potential
      candidates include older patients with low-risk cancers and urinary obstruction.
      Further prospective reports are necessary to evaluate functional and oncological
      outcome for this innovative technique.

PMID- 21739125
TI  - Specific body mass index cut-off value in relation to survival of patients with
      upper urinary tract urothelial carcinomas.
AB  - PURPOSE: We studied the prognostic value of body mass index (BMI) in patients
      with upper tract urothelial carcinoma (UTUC) of the kidney and ureter. METHODS:
      We evaluated 153 patients who underwent surgery for UTUC (any T stage, N0-1, M0)
      between 1996 and 2009 at our institution. Of the 153 patients screened for the
      study, 103 patients were found to have comprehensive clinical and pathologic data
      available, and were included in the analysis. Patients were stratified by BMI =
      22 kg/m(2) or greater versus less than 22. Overall survival (OS), cancer-specific
      survival (CSS), and recurrence-free survival was estimated using the Kaplan-Meier
      method. Multivariate analysis was performed with the Cox regression model.
      RESULTS: The mean age and BMI of all patients was 68.62 +/- 10.06 years and 22.97
      +/- 3.44 kg/m(2), respectively. The patient population comprised 71 (68.9%) males
      and 32 (31.1%) females. The BMI was <22 in 38 (36.9%) patients and >22 in 65
      (63.1%). The differences between BMI categories in gender (p = 0.013) was
      statistically significant, but not in other relevant parameters. The median
      follow-up was 29 months (interquartile range 14-63). Among other relevant
      descriptive preoperative characteristics, including gender, age, bladder tumor at
      diagnosis, tumor focality, and tumor side, smaller BMI remained an independent
      predictor for worse CSS (p = 0.047, HR 2.210) on multivariate analysis.
      CONCLUSIONS: Our findings identify increasing BMI as an independent predictor for
      favorable OS and CSS in patients with UTUC.

PMID- 21739126
TI  - Neonatal testicular torsion: a systematic literature review.
AB  - Neonatal testicular torsion (NTT) is rare and reported salvage rates vary widely
      both in their cited frequency and plausibility. The timing and necessity of
      surgery is controversial with different centers arguing for the conservative
      management of all cases while others argue for prompt exploration for all.
      Confusion also reigns over the need to fix the contralateral testis. In order to
      clarify the issue the authors reviewed the literature and found 18 case series of
      NTT, containing 268 operated cases suitable for analysis. This paper reviews the
      literature on NTT specifically regarding salvage rates and timing/necessity of
      surgery. Its primary aim is to produce an overall salvage rate in the operated
      group. Overall salvage rate was 8.96%, 24 testes. When operation is specified as
      an emergency, salvage may be as high as 21.7%. While salvage of a testis torted
      at birth is rare, it is reported. Early asynchronous torsion is also rare but
      reported. Worryingly, bilateral torsion can present with unilateral signs.Given
      these findings, we would suggest early surgery with fixation of the contralateral
      side.

PMID- 21739127
TI  - Congenital extrahepatic portosystemic shunt (Abernethy malformation) treated
      endovascularly with vascular plug shunt closure.
AB  - A 3-year-old boy, who presented with progressive cyanosis and hypoxia, was
      diagnosed with a large congenital extrahepatic portosystemic shunt, interrupted
      IVC with azygos continuation, and multiple congenital anomalies. Traditionally
      open and laparoscopic surgical techniques have been used to treat this
      malformation. Endovascular repair using a 16-mm Amplatzer vascular plug (AGA
      Medical Corporation, Golden Valley, Minnesota, USA) was used to occlude the
      shunt. Immediate post-placement venography demonstrated cessation of flow within
      the shunt and increased portal venous flow. The patient's hypoxia and cyanosis
      decreased significantly, and he was discharged on the 5th post-procedure day in
      stable clinical condition. Three months follow-up evaluation demonstrated the
      vascular plug in place, unchanged in position.

PMID- 21739128
TI  - Understanding multisymptom presentations in chronic pelvic pain: the inter
      relationships between the viscera and myofascial pelvic floor dysfunction.
AB  - Patients presenting with chronic pelvic pain frequently complain of multiple
      symptoms that appear to involve more than one organ system, creating diagnostic
      confusion. The multisymptom presentation of chronic pelvic pain has been
      frequently described. This article describes four proposed explanations for the
      clinical observation of multisymptom presentations of patients with chronic
      pelvic pain. These include the concepts of viscerovisceral convergence;
      viscerosomatic convergence; hypertonicity of pelvic floor muscles creating
      visceral symptoms along with somatovisceral convergence; and central
      sensitization with expansion of receptive fields.

PMID- 21739129
TI  - Bone mineral density in familial Mediterranean fever.
AB  - The aim of this study was to evaluate the bone mineral density (BMD) in familial
      Mediterranean fever (FMF) and to search the effects of genetic factors, family
      history of FMF and types of clinical attacks on BMD. Forty-four attack-free
      patients with FMF and 36 healthy voluntary subjects were included in the study.
      BMD measurements of lumbar spine and left proximal femur were performed by dual
      energy X-ray absorptiometry (DEXA). There was no statistically significant
      difference between patient and control groups regarding median values of lumbar
      BMD (P = 0.06), lumbar T (P = 0.08) and Z (P = 0.12) scores, femoral neck BMD (P
      = 0.13), femoral T (P = 0.22) and Z (P = 0.16) scores and total femur BMD (P =
      0.14), T (P = 0.19) and Z (P = 0.27) scores. Patients with negative FMF family
      history had significantly lower femoral neck BMD (P = 0.018), femoral neck T (P =
      0.009) and Z (P = 0.01) scores and total femur BMD (P = 0.033) than patients with
      positive FMF family history. There was no significant difference among the groups
      regarding mutation characteristic and types of attacks in lumbar BMD, T and Z
      scores, femoral neck BMD, T and Z scores and total femur BMD, T and Z scores (P >
      0.05). We found that the bone loss of patients with FMF is not different from
      that of the controls. The increased bone loss in the patients with negative
      family history for FMF should be further investigated with larger patient groups
      taking into consideration of the risk factors related to family history for
      osteoporosis.

PMID- 21739130
TI  - Prospective thinking in a mustelid? Eira barbara (Carnivora) cache unripe fruits
      to consume them once ripened.
AB  - The ability of nonhuman animals to project individual actions into the future is
      a hotly debated topic. We describe the caching behaviour of tayras (Eira barbara)
      based on direct observations in the field, pictures from camera traps and radio
      telemetry, providing evidence that these mustelids pick and cache unripe fruit
      for future consumption. This is the first reported case of harvesting of unripe
      fruits by a nonhuman animal. Ripe fruits are readily taken by a variety of
      animals, and tayras might benefit by securing a food source before strong
      competition takes place. Unripe climacteric fruits need to be harvested when
      mature to ensure that they continue their ripening process, and tayras accurately
      choose mature stages of these fruits for caching. Tayras cache both native
      (sapote) and non-native (plantain) fruits that differ in morphology and
      developmental timeframes, showing sophisticated cognitive ability that might
      involve highly developed learning abilities and/or prospective thinking.

PMID- 21739131
TI  - Avoiding incidental predation by mammalian herbivores: accurate detection and
      efficient response in aphids.
AB  - Mammalian herbivores eat plants that may also provide food and shelter for
      insects. The direct trophic effect of the browsing and grazing of mammalian
      herbivory on insects, which is probably prevalent in terrestrial ecosystems, has
      been mostly neglected by ecologists. We examined how the aphid Uroleucon sonchi
      L. deals with the danger of incidental predation by mammalian herbivores. We
      found that most (76%) of the aphids in a colony survive the ingestion of the
      plant by a feeding herbivore. They do so by sensing the combination of heat and
      humidity in the herbivore's breath and immediately dropping off the plant in
      large numbers. Their ability to sense the herbivore's breath or their tendency to
      drop off the plant weakens as ambient temperature rises. This could indicate a
      limitation of the aphids' sensory system or an adaptation that enables them to
      avoid the hostile conditions on a hot ground. Once on the ground, U. sonchi is
      highly mobile and capable of locating a new host plant by advancing in a pattern
      that differs significantly from random movement. The accurate and efficient
      defense mechanism of U. sonchi emphasizes the significance of incidental
      predation as a danger to plant-dwelling invertebrates.

PMID- 21739132
TI  - Thermoregulation and performance of British Anglo-Nubian and Saanen goats reared
      in an intensive system in Trinidad.
AB  - Anglo-Nubian and Saanen goats were imported into Trinidad and Tobago to form the
      nucleus of the goat expansion and improvement programme. Thermoregulation and
      performance of the parent stock and the F1 were evaluated under intensive housing
      and management. Rectal temperature in the A.M.:  irrespective of breed or season
      ranged from 38.5 degrees C to 38.7 degrees C and P.M.:  ranged from 38.8 degrees
      C to 39.0 degrees C. After 2 h of exposure outdoors without shade, Saanen parent
      stock (SAPS) respiration rate (105 br/min) was significantly higher (p < 0.001)
      than Saanen F1 (SAF1, 76 br/min), Anglo-Nubian parent stock (ANSP, 65 br/min) and
      Anglo-Nubian F1 (ANF1, 51 br/min). Rectal temperature over the same period showed
      significant differences (p < 0.042) between SAF1 (39.8 degrees C) and SAPS (39.4
      degrees C), and ANF1 (39.4 degrees C); the value for ANSP was 39.7 degrees C. Age
      at first kidding showed no significant difference (p > 0.05) between breeds or
      between the parent stock and the F1 generations, ranging from 638 to 686 days.
      The ANPS were the most prolific of all groups (p < 0.05); the mean for this group
      was 1.86 +/- 0.07 kids/kidding. Saanen F1 was the least prolific among the group,
      with mean number of kids at 1.23 (+/-0.11) kids/kidding. Kidding interval showed
      no significant (p > 0.05) difference between the groups, ranging from 319 to 521
      days. It was concluded that the Anglo-Nubian appears to be more suitable than the
      Saanen for the tropical humid environment in Trinidad as indicated by their
      thermoregulation, prolificacy and kidding interval.

PMID- 21739133
TI  - Application of DNA markers in parentage verification of Boran cattle in Kenya.
AB  - Boran cattle provide livelihood to thousands of households in the arid and
      semiarid lands of Kenya. Due to their superior adaptive and productive traits in
      comparison to other breeds of cattle, they have also become a popular choice for
      breeders in Eastern and Southern Africa. Continued genetic improvement of the
      breed is important, and therefore accurate performance and pedigree records are
      required. One hundred seventy-eight pedigree records and blood samples of four
      Boran stud herds were evaluated for accuracy of parentage allocation using 11
      microsatellite markers recommended by ISAG for parentage verification. The panel
      of the 11 microsatellite markers was found to be highly polymorphic (PIC of
      0.6901) with a combined probability of exclusion of 0.9997. The dam
      misidentification was low ranging between 0% and 5% for the herds tested. The
      estimated rate of mispaternity however ranged between 4.3% and 80% among the four
      stud herds, and more than 50% of the offspring of some herds were misidentified.
      The high rate of mispaternity will have a negative impact on the response to
      selection. The use of DNA markers for parentage assignment will improve the
      accuracy of the pedigree records of Boran stud cattle in Kenya and contribute to
      more accurate selection of superior animals.

PMID- 21739134
TI  - Differences between seroreactivity to leptospirosis in dairy and beef cattle from
      the same herd in Rio de Janeiro, Brazil.

PMID- 21739135
TI  - Object permanence in adult common marmosets (Callithrix jacchus): not everything
      is an "A-not-B" error that seems to be one.
AB  - In this paper, we describe a behaviour pattern similar to the "A-not-B" error
      found in human infants and young apes in a monkey species, the common marmosets
      (Callithrix jacchus). In contrast to the classical explanation, recently it has
      been suggested that the "A-not-B" error committed by human infants is at least
      partially due to misinterpretation of the hider's ostensively communicated object
      hiding actions as potential 'teaching' demonstrations during the A trials. We
      tested whether this so-called Natural Pedagogy hypothesis would account for the A
      not-B error that marmosets commit in a standard object permanence task, but found
      no support for the hypothesis in this species. Alternatively, we present evidence
      that lower level mechanisms, such as attention and motivation, play an important
      role in committing the "A-not-B" error in marmosets. We argue that these simple
      mechanisms might contribute to the effect of undeveloped object representational
      skills in other species including young non-human primates that commit the A-not
      B error.

PMID- 21739136
TI  - Domestic dogs (Canis familiaris) flexibly adjust their human-directed behavior to
      the actions of their human partners in a problem situation.
AB  - Domestic dogs (Canis familiaris) have been shown to actively initiate triadic
      communicative interactions by looking at a human partner or by alternating their
      gaze between the human and an object when being faced with an out-of-reach reward
      or an unsolvable problem. It has hardly been investigated, however, whether dogs
      flexibly adjust their human-directed behavior to the actions of their partners,
      which indicate their willingness and abilities to help them when they are faced
      with a problem. Here, in two experiments, we confronted dogs-after initially
      allowing them to learn how to manipulate an apparatus-with two problem
      situations: with an empty apparatus and a blocked apparatus. In Experiment 1, we
      showed that dogs looked back at their owners more when the owners had previously
      encouraged them, independently from the problem they faced. In Experiment 2, we
      provided dogs with two experimenters and allowed them to learn through an initial
      phase that each of the experimenters could solve one of the two problems: the
      Filler re-baited the empty apparatus and the Helper unblocked the blocked
      apparatus. We found that dogs could learn to recognize the ability of the Filler
      and spent time close to her when the apparatus was empty. Independently from the
      problem, however, they always approached the Helper first. The results of the
      present study indicate that dogs may have a limited understanding of physical
      problems and how they can be solved by a human partner. Nevertheless, dogs are
      able to adjust their behavior to situation-specific characteristics of their
      human partner's behavior.

PMID- 21739137
TI  - Application of support vector regression to genome-assisted prediction of
      quantitative traits.
AB  - A byproduct of genome-wide association studies is the possibility of carrying out
      genome-enabled prediction of disease risk or of quantitative traits. This study
      is concerned with predicting two quantitative traits, milk yield in dairy cattle
      and grain yield in wheat, using dense molecular markers as predictors. Two
      support vector regression (SVR) models, epsilon-SVR and least-squares SVR, were
      explored and compared to a widely applied linear regression model, the Bayesian
      Lasso, the latter assuming additive marker effects. Predictive performance was
      measured using predictive correlation and mean squared error of prediction.
      Depending on the kernel function chosen, SVR can model either linear or nonlinear
      relationships between phenotypes and marker genotypes. For milk yield, where
      phenotypes were estimated breeding values of bulls (a linear combination of the
      data), SVR with a Gaussian radial basis function (RBF) kernel had a slightly
      better performance than with a linear kernel, and was similar to the Bayesian
      Lasso. For the wheat data, where phenotype was raw grain yield, the RBF kernel
      provided clear advantages over the linear kernel, e.g., a 17.5% increase in
      correlation when using the epsilon-SVR. SVR with a RBF kernel also compared
      favorably to the Bayesian Lasso in this case. It is concluded that a nonlinear
      RBF kernel may be an optimal choice for SVR, especially when phenotypes to be
      predicted have a nonlinear dependency on genotypes, as it might have been the
      case in the wheat data.

PMID- 21739138
TI  - Precise mapping Fhb5, a major QTL conditioning resistance to Fusarium infection
      in bread wheat (Triticum aestivum L.).
AB  - Qfhi.nau-5A is a major quantitative trait locus (QTL) against Fusarium
      graminearum infection in the resistant wheat germplasm Wangshuibai. Genetic
      analysis using BC(3)F(2) and BC(4)F(2) populations, derived from selfing two near
      isogenic lines (NIL) heterozygous at Qfhi.nau-5A that were developed,
      respectively, with Mianyang 99-323 and PH691 as the recurrent parent, showed that
      Qfhi.nau-5A inherited like a single dominant gene. This QTL was thus designated
      as Fhb5. To fine map it, these two backcross populations and a recombinant inbred
      line (RIL) population derived from Nanda2419 * Wangshuibai were screened for
      recombinants occurring between its two flanking markers Xbarc56 and Xbarc100.
      Nineteen NIL recombinants were identified from the two backcross populations and
      nine from the RIL population. In the RIL recombinant selection process, selection
      against Fhb4 present in the RIL population was incorporated. Genotyping these
      recombinant lines with ten markers mapping to the Xbarc56-Xbarc100 interval
      revealed four types of Mianyang 99-323-derived NIL recombinants, three types of
      PH691-derived NIL recombinants, and four types of RIL recombinants. In different
      field trials, the percentage of infected spikes of these lines displayed a
      distinct two-peak distribution. The more resistant class had over 55% less
      infection than the susceptible class. Common to these resistant genotypes, the
      0.3-cM interval flanked by Xgwm304 and Xgwm415 or one of these two loci was
      derived from Wangshuibai, while none of the susceptible recombinants had
      Wangshuibai chromatin in this interval. This interval harboring Fhb5 was mapped
      to the pericentromeric C-5AS3-0.75 bin through deletion bin mapping. The precise
      localization of Fhb5 will facilitate its utilization in marker-assisted wheat
      breeding programs.

PMID- 21739139
TI  - Resistance to powdery mildew in Spanish barley landraces is controlled by
      different sets of quantitative trait loci.
AB  - Twenty-two landrace-derived inbred lines from the Spanish Barley Core Collection
      (SBCC) were found to display high levels of resistance to a panel of 27 isolates
      of the fungus Blumeria graminis that exhibit a wide variety of virulences. Among
      these lines, SBCC145 showed high overall resistance and a distinctive spectrum of
      resistance compared with the other lines. Against this background, the main goal
      of the present work was to investigate the genetic basis underlying such
      resistance using a doubled haploid population derived from a cross between
      SBCC145 and the elite spring cultivar Beatrix. The population was genotyped with
      the 1,536-SNP Illumina GoldenGate Oligonucleotide Pool Assay (Barley OPA-1 or
      BOPA1 for short), whereas phenotypic analysis was performed using two B. graminis
      isolates. A major quantitative trait locus (QTL) for resistance to both isolates
      was identified on the long arm of chromosome 6H (6HL) and accounted for ca. 60%
      of the phenotypic variance. Depending on the B. graminis isolate tested, three
      other minor QTLs were detected on chromosomes 2H and 7H, which explained less
      than 5% of the phenotypic variation each. In all cases, the alleles for
      resistance derived from the Spanish parent SBCC145. The position, the magnitude
      of the effect observed and the proportion of phenotypic variation accounted for
      by the QTL on 6HL suggest this is a newly identified locus for broad-based
      resistance to powdery mildew.

PMID- 21739140
TI  - Chromosome 5H of Hordeum species involved in reduction in grain hardness in wheat
      genetic background.
AB  - Grain hardness is an important factor affecting end-use quality in wheat.
      Mutations of the puroindoline genes, which are located on chromosome 5DS, control
      a majority of grain texture variations. Hordoindoline genes, which are the
      puroindoline gene homologs in barley, are located on chromosome 5HS and are also
      responsible for grain texture variation. In this study, we used three types of
      wheat-barley species (Hordeum vulgare, H. vulgare ssp. spontaneum, and H.
      chilense) chromosome addition lines and studied the effect of chromosome 5H of
      these species on wheat grain characteristics. The 5H chromosome addition lines
      showed significantly lower grain hardness and higher grain weight than the
      corresponding wheat parents. The effect of enhancing grain softness was largest
      in the wheat-H. chilense line regardless of having an increase in grain weight
      similar to those in the wheat-H. vulgare and wheat-H. spontaneum lines. Our
      results indicated that chromosome 5H of the Hordeum species plays a role in
      enhancing grain softness and increasing grain weight in the wheat genetic
      background, and the extent of effect on grain hardness depends on the type of
      Hordeum species. Protein analysis of hordoindolines indicated that profiles of 2D
      electrophoresis of hordoindolines were different among Hordeum species and
      hordoindolines in the addition lines appeared to be most abundant in wheat-H.
      chilense line. The differences in enhancing grain softness among the Hordeum
      species might be attributed to the quantity of hordoindolines expressed in the 5H
      chromosome addition lines. These results suggested that the barley hordoindolines
      located on chromosome 5HS play a role in reducing grain hardness in the wheat
      genetic background.

PMID- 21739141
TI  - QTL for fibre-related traits in grain * sweet sorghum as a tool for the
      enhancement of sorghum as a biomass crop.
AB  - Compared to maize and temperate grasses, sorghum has received less attention in
      terms of improving cell wall components. The objectives of this study were to
      identify quantitative trait loci (QTL) with main effects, epistatic and
      pleiotropic effects along with QTL * environment (QE) interactions controlling
      fibre-related traits in sorghum. Neutral detergent fibre (NDF), acid detergent
      fibre (ADF), acid detergent lignin (ADL), cellulose, hemicellulose, fresh leaf
      mass, stripped stalk mass, dry stalk mass, fresh biomass and dry biomass were
      analysed from a population of 188 grain * sweet sorghum recombinant inbred lines.
      A genetic map consisting of 157 DNA markers was constructed, and QTL were
      detected using composite interval mapping (CIM). CIM detected more than 5
      additive QTL per trait explaining 7.1-24.7% of the phenotypic variation. Abundant
      co-localization of these QTL was observed across all chromosomes, and the highest
      cluster was identified on chromosome 6. Searching for candidate genes using the
      confidence interval of our QTL clusters reveals that these clusters might
      comprise a set of genes that are tightly linked. Some QTL showed multiple
      effects; however, the allele for each trait was favouring the parent with the
      increasing effect. QE interactions were observed for QTL showing multiple
      effects. Additive * additive interaction was observed for 7 out of 10 traits,
      indicating the importance of epistatic analysis. However, the phenotypic
      variation explained by digenic interactions was lower compared to the individual
      QTL. Our results indicate that various genetic components contribute to fibre
      related traits and should be considered during the enhancement of sorghum for
      lignocellulosic biomass.

PMID- 21739142
TI  - Association and expression study of MMP3, TGFbeta1 and COL10A1 as candidate genes
      for leg weakness-related traits in pigs.
AB  - The present study was aimed to determine the association between
      metalloproteinase 3 (MMP3), transforming growth factor beta 1 (TGFbeta1) and
      collagen type X alpha I (COL10A1) gene polymorphisms with traits related to leg
      weakness in pigs. Three hundred Duroc * Pietrain cross breds (DuPi) and 299 pigs
      of a commercial population (CP) were used for the experiment. DuPi animals were
      examined for 10 different traits describing leg and feet structure,
      osteochondrosis (OC) scores and bone density status. Data of OC score at condylus
      medialis humeri, condylus medialis femoris and distal epiphysis ulna regions of
      CP were used for association analysis. Significant association (P < 0.05) was
      found for MMP3 SNP (g.158 C>T) with OC at head of femur and bone mineral density
      in the DuPi population. Association (P < 0.05) was found between SNP of TGFbeta1
      (g.180 G>A) with rear leg score and the principle component denoting both OC and
      feet and leg scores in the DuPi population. No association was found between
      COL10A1 (g.72 C>T) and leg weakness related traits. The associations of SNPs with
      OC traits could not be confirmed in the commercial population. Expression
      analysis of the three candidate genes was performed to compare between healthy
      and OC. TGFbeta1 was found to be highly expressed (P < 0.05) in the OC compared
      to healthy cartilages, but no significant different expressions were observed for
      MMP3 and COL10A1 genes. The present finding suggested that TGFbeta1 and MMP3
      genes variants have an effect on some of the leg weakness related traits.

PMID- 21739143
TI  - The expression level of Rosa Terminal Flower 1 (RTFL1) is related with recurrent
      flowering in roses.
AB  - We examined the relationship between the recurrent flowering character and the
      expression patterns of TERMINAL FLOWER 1 (TFL1) homologs in roses, using flower
      buds of Rosa multiflora, R. rugosa, R. chinensis, and six other rose species and
      nine rose cultivars. RTFL1 (Rosa TFL1) genes were amplified from rose genomic DNA
      using a combination of degenerate and gene-specific primers by thermal asymmetric
      interlaced-PCR and normal PCR, respectively. Their copy numbers in different
      species were determined by Southern blots. We used real-time PCR to analyze the
      expression patterns of RTFL1 genes at four developmental stages (pre-sprouting,
      young, mid-aged, and mature flower buds). Our results show that there are at
      least three RTFL1 homologs in roses; RTFL1a, RTFL1b, and RTFL1c. The sequences of
      the homologs were more similar among the same homolog in different species than
      among the different homologs in the same species. For RTFL1a, we detected two
      copies in R. multiflora, two copies in R. rugosa, and one copy in R. chinensis.
      For RTFL1c, we detected one copy in R. multiflora, two copies in R. rugosa, and
      three copies in R. chinensis. We detected only one copy of RTFL1b in R.
      chinensis. RTFL1c was expressed at high levels at all four flowering stages in R.
      multiflora and R. rugosa, which are non-recurrent flowering species, whereas it
      was barely detected in R. chinensis (a recurrent flowering species) at any stage.
      These results were further verified in six other non-recurrent flowering species
      and nine recurrent flowering cultivars. These results suggest that the recurrent
      flowering habit in roses results from lower expression of RTFL1c, which may be
      related to recurrent flowering character in roses.

PMID- 21739144
TI  - A polymorphism in the YWHAH gene encoding 14-3-3 eta that is not associated with
      sporadic Creutzfeldt-Jakob disease (CJD).
AB  - 14-3-3 proteins are abundantly expressed in the brain, particularly neuronal
      tissue and are thought to serve multiple biological functions involved in
      neuronal development and cell growth and death. Recent studies have shown
      associations of 14-3-3 genes with neurodegenerative disorders based on their
      chromosomal linkage to these diseases and to regulatory functions for the nervous
      system. Although the role of 14-3-3 proteins in the pathogenesis of prion
      diseases remains unknown, the detection of altered levels of isoforms of the 14-3
      3 protein in the cerebrospinal fluid is considered a biomarker for diagnosis of
      sporadic Creutzfeldt-Jakob disease (sCJD). To identify other susceptibility genes
      for prion disease, we examined nucleotide variations in YWHAH, a gene encoding 14
      3-3 eta. This case-control study included 182 sCJD patients and 206 healthy
      Koreans. Polymerase chain reaction was used to amplify open reading frame and
      some 3'-untranslated region (UTR) in exon 2, and direct sequencing was carried
      out. One polymorphism, 753 G/A, was detected in the 3'-UTR of exon 2 on the
      YWHAH. The genotype distribution and allele frequencies of the YWHAH 753 G/A
      polymorphism were not significantly different between controls and sCJD patients.
      This finding indicates that YWHAH 753 G/A polymorphism is unlikely to be linked
      to genetic susceptibility or have a modifying effect in sCJD. On analysis
      stratified by the prion protein gene 129 or 219 genotype, no significant relation
      was found in genotype and allele frequencies of the YWHAH 753G/A. This is the
      first genetic association study of YWHAH with sCJD populations.

PMID- 21739145
TI  - Cloning and characterization of a Verticillium wilt resistance gene from
      Gossypium barbadense and functional analysis in Arabidopsis thaliana.
AB  - Verticillium wilt causes enormous loss to yield or quality in many crops. In an
      effort to help controlling this disease through genetic engineering, we first
      cloned and characterized a Verticillium wilt resistance gene (GbVe) from cotton
      (Gossypium barbadense) and analyzed its function in Arabidopsis thaliana. Its
      nucleotide sequence is 3,819 bp long, with an open reading frame of 3,387 bp, and
      encoding an 1,128-aa protein precursor. Sequence analysis shows that GbVe
      produces a leucine-rich repeat receptor-like protein. It shares identities of
      55.9% and 57.4% with tomato Ve1 and Ve2, respectively. Quantitative real-time PCR
      indicated that the Ve gene expression pattern was different between the resistant
      and susceptible cultivars. In the resistant Pima90-53, GbVe was quickly induced
      and reached to a peak at 2 h after inoculation, two-fold higher than that of
      control. We localized the GbVe-GFP fusion protein to the cytomembrane in onion
      epidermal cells. By inserting GbVe into Arabidopsis via Agrobacterium-mediated
      transformation, T(3) transgenic lines were obtained. Compared with the wild-type
      control, GbVe-overexpressing plants had greater levels of resistance to V.
      dahliae. This suggests that GbVe is a useful gene for improving the plant
      resistance against fungal diseases.

PMID- 21739146
TI  - Role of HD2 genes in seed germination and early seedling growth in Arabidopsis.
AB  - The Arabidopsis HD2 family of histone deacetylases consist of 4 members (HD2A,
      HD2B, HD2C, HD2D) that play diverse roles in plant development and physiology
      through chromatin remodelling. Here, we show that the transcripts of HD2 family
      members selectively accumulate in response to glucose through a HXK1-independent
      signal transduction pathway during the early stages of seedling growth.
      Germination was enhanced in hd2a null mutants relative to wild-type seeds. In
      contrast, hd2c mutants were restrained in germination relative to wild-type
      seeds. In hd2a/hd2c double mutants, germination was restored to wild-type levels.
      The data suggests that HD2A and HD2C may have different and opposing functions in
      germination with the glucose/HD2A pathway acting to restrain germination and the
      HD2C pathway acting to enhance germination. These pathways may function early in
      the regulation of seedling germination, independently of the glucose/HXK1/ABA
      signal transduction pathway, to fine tune the onset of germination.

PMID- 21739147
TI  - Photorelease of amino acids from novel thioxobenzo[f]benzopyran ester conjugates.
AB  - Aiming at the enhancement of the performance of (9-methoxy-3-oxo-3H
      benzo[f]benzopyran-1-yl) methyl ester as photocleavable protecting group for the
      carboxylic acid function at long-wavelengths, 9-methoxy-3-thioxo-3H
      benzo[f]benzopyran-L-valine and L-phenylalanine model conjugates were prepared
      through a thionation reaction of the corresponding oxo-benzobenzopyrans. These
      thioxobenzobenzopyran derivatives were subjected to photocleavage reactions in
      the same conditions as the parent oxo-benzobenzopyrans at different wavelengths
      of irradiation, and photocleavage data were obtained. It was found that the
      exchange of the carbonyl by a thiocarbonyl group enhanced the performance of the
      heterocyclic protecting group at 419 nm by improving the photolysis rates, making
      it an appropriate group for practical applications at long wavelengths.

PMID- 21739148
TI  - Taurine transporter gene expression in peripheral mononuclear blood cells of type
      2 diabetic patients.
AB  - Taurine acts as antioxidant, cell osmolyte, modulator of glucose metabolism, and
      plays a role in the retinal function. It is 10(3)-fold more concentrated in the
      intracellular than in the extracellular milieu due to a specific taurine-Na
      dependent transporter (TauT), which is upregulated by hypertonicity, low
      extracellular taurine, or oxidative stress and acutely downregulated 'in vitro'
      by high glucose concentrations. Aim of this study was to investigate whether TauT
      expression was modified in mononuclear peripheral blood cells (MPC) of type 2
      diabetic patients with or without micro/macrovascular complications. Plasma
      taurine, as well as other sulphur-containing aminoacids (assayed by HPLC) and
      TauT gene expression (assayed by real-time PCR analysis) were measured in MPC of
      45 controls and of 81 age-and-sex matched type 2 diabetic patients with or
      without micro/macrovascular complications. Median value (interquartile range) of
      plasma taurine was significantly lower in diabetic patients than in controls
      [28.7 (13.7) MUmol/l vs. 46.5 (20.3) MUmol/l; P<0.05], while median TauT
      expression, in arbitrary units, was significantly higher in diabetics than in
      controls [3.8 (3.9) vs. 1 (1.3); P<0.05) and was related to HbA1c only in
      controls (r=0.34; P<0.05). Patients with retinopathy (n=25) had lower TauT
      expression than those who were unaffected [3.1 (2.8) vs. 4.1 (3.4); P<0.05],
      while persistent micro/macroalbuminuria was associated with unchanged TauT
      expression. A trend toward reduction in TauT expression was observed in patients
      with macroangiopathy [n=27; 3.3 (2.5) vs. 4 [3.7]; P=NS]. In conclusion, TauT
      gene is overexpressed in MPC of type 2 diabetic patients, while presence of
      retinopathy is specifically associated with a drop in TauT overexpression,
      suggesting its possible involvement in this microangiopathic lesion.

PMID- 21739150
TI  - Pharmacological inhibition of HSP90 activity negatively modulates myogenic
      differentiation and cell survival in C2C12 cells.
AB  - Heat-shock protein90 (HSP90) plays an essential role in maintaining stability and
      activity of its clients. HSP90 is involved in cell differentiation and survival
      in a variety of cell types. To elucidate the possible role of HSP90 in myogenic
      differentiation and cell survival, we examined the time course of changes in the
      expression of myogenic regulatory factors, intracellular signaling molecules, and
      anti-/pro-apoptotic factors when C2C12 cells were cultured in differentiation
      condition in the presence of a HSP90-specific inhibitor, geldanamycin.
      Furthermore, we examined the effects of geldanamycin on muscle regeneration in
      vivo. Our results showed that geldanamycin inhibited myogenic differentiation
      with decreased expression of MyoD, myogenin and reduced phosphorylation levels of
      Akt1. Geldanamycin had little effect on the phosphorylation levels of p38MAPK and
      ERK1/2 but reduced the phosphorylation levels of JNK. Along with myogenic
      differentiation, geldanamycin increased apoptotic nuclei with decreased
      expression of Bcl-2. The skeletal muscles forced to regenerate in the presence of
      geldanamycin were of poor repair with small regenerating myofibers and increased
      connective tissues. Together, our findings suggest that HSP90 may modulate
      myogenic differentiation and may be involved in cell survival.

PMID- 21739151
TI  - Homocysteine-induced cardiomyocyte apoptosis and plasma membrane flip-flop are
      independent of S-adenosylhomocysteine: a crucial role for nuclear p47(phox).
AB  - We previously found that homocysteine (Hcy) induced plasma membrane flip-flop,
      apoptosis, and necrosis in cardiomyocytes. Inactivation of flippase by Hcy
      induced membrane flip-flop, while apoptosis was induced via a NOX2-dependent
      mechanism. It has been suggested that S-adenosylhomocysteine (SAH) is the main
      causative factor in hyperhomocysteinemia (HHC)-induced pathogenesis of
      cardiovascular disease. Therefore, we evaluated whether the observed cytotoxic
      effect of Hcy in cardiomyocytes is SAH dependent. Rat cardiomyoblasts (H9c2
      cells) were treated under different conditions: (1) non-treated control (1.5 nM
      intracellular SAH with 2.8 MUM extracellular L -Hcy), (2) incubation with 50 MUM
      adenosine-2,3-dialdehyde (ADA resulting in 83.5 nM intracellular SAH, and 1.6 MUM
      extracellular L -Hcy), (3) incubation with 2.5 mM D, L -Hcy (resulting in 68 nM
      intracellular SAH and 1513 MUM extracellular L -Hcy) with or without 10 MUM
      reactive oxygen species (ROS)-inhibitor apocynin, and (4) incubation with 100 nM,
      10 MUM, and 100 MUM SAH. We then determined the effect on annexin V/propodium
      iodide positivity, flippase activity, caspase-3 activity, intracellular NOX2 and
      p47(phox) expression and localization, and nuclear ROS production. In contrast to
      Hcy, ADA did not induce apoptosis, necrosis, or membrane flip-flop. Remarkably,
      both ADA and Hcy induced a significant increase in nuclear NOX2 expression.
      However, in contrast to ADA, Hcy additionally induced nuclear p47(phox)
      expression, increased nuclear ROS production, and inactivated flippase.
      Incubation with SAH did not have an effect on cell viability, nor on flippase
      activity, nor on nuclear NOX2-, p47phox expression or nuclear ROS production. HHC
      induced membrane flip-flop and apoptosis in cardiomyocytes is due to increased
      Hcy levels and not primarily related to increased intracellular SAH, which plays
      a crucial role in nuclear p47(phox) translocation and subsequent ROS production.

PMID- 21739152
TI  - About the role of CK2 in plant signal transduction.
AB  - Despite increasing progress in the study of CK2 activity in plants, a clear
      understanding of its functional role remains elusive. The high pleiotropic nature
      of the enzyme, the fact that it is absolutely necessary to maintain life, and the
      existence of multiple isoforms have made it difficult to obtain loss-of-function
      mutants with which to study the impact of CK2 depletion in the organisms. To
      avoid all these difficulties, we have used a dominant-negative mutant approach,
      by constructing a CK2alpha kinase-inactive subunit (CKA3mut) that was cloned
      downstream of an inducible promoter. Stably transformed Arabidopsis plants showed
      that longtime inductions of the transgene were lethal, causing growth and
      development arrests and ultimately resulting in plant death. However, short-time
      inductions were not lethal and revealed broad phenotypical changes that uncovered
      novel functions of CK2 in plants. The high pleiotropy of CK2 was sustained by
      analysis of global transcript profiles that showed a huge number of genes
      affected, involved in a wide variety of cellular processes.

PMID- 21739153
TI  - Enzymatic activity with an incomplete catalytic spine: insights from a
      comparative structural analysis of human CK2alpha and its paralogous isoform
      CK2alpha'.
AB  - Eukaryotic protein kinases are fundamental factors for cellular regulation and
      therefore subject of strict control mechanisms. For full activity a kinase
      molecule must be penetrated by two stacks of hydrophobic residues, the regulatory
      and the catalytic spine that are normally well conserved among active protein
      kinases. We apply this novel spine concept here on CK2alpha, the catalytic
      subunit of protein kinase CK2. Homo sapiens disposes of two paralog isoforms of
      CK2alpha (hsCK2alpha and hsCK2alpha'). We describe two new structures of
      hsCK2alpha constructs one of which in complex with the ATP-analog adenylyl
      imidodiphosphate and the other with the ATP-competitive inhibitor 3-(4,5,6,7
      tetrabromo-1H-benzotriazol-1-yl)propan-1-ol. The former is the first hsCK2alpha
      structure with a well defined cosubstrate/magnesium complex and the second with
      an open beta4/beta5-loop. Comparisons of these structures with existing
      CK2alpha/CK2alpha' and cAMP-dependent protein kinase (PKA) structures reveal: in
      hsCK2alpha' an open conformation of the interdomain hinge/helix alphaD region
      that is critical for ATP-binding is found corresponding to an incomplete
      catalytic spine. In contrast hsCK2alpha often adopts the canonical, PKA-like
      version of the catalytic spine which correlates with a closed conformation of the
      hinge region. HsCK2alpha can switch to the incomplete, non-canonical, hsCK2alpha'
      like state of the catalytic spine, but this transition apparently depends on
      binding of either ATP or of the regulatory subunit CK2beta. Thus, ATP looks like
      an activator of hsCK2alpha rather than a pure cosubstrate.

PMID- 21739154
TI  - Stimulation of CK2-dependent Grp94 phosphorylation by the nuclear localization
      signal peptide.
AB  - The nuclear localization signal sequence (NLS) of SV40 Large T antigen is
      essential and sufficient for the nuclear translocation of the protein.
      Phosphorylation often modulates the intracellular distribution of signaling
      proteins. In this study, we investigated effects of the NLS-peptide of Large T
      antigen on protein phosphorylation. When crude cell lysates were incubated with
      [gamma-(32)P]ATP, phosphorylation of several endogenous substrates with molecular
      masses of 100, 80, 50, and 45 kDa by an endogenous kinase was stimulated by the
      addition of the wild type NLS-peptide (CPKKKRKVEDP). The mutated NLS-peptide
      (CPKTKRKVEDP) and the reversed NLS-peptide (PDEVKRKKKPC) are weak in the nuclear
      localization activity, and they only weakly stimulated phosphorylation of these
      substrates. The mobility of the 100 kDa phosphoprotein was indistinguishable with
      that of an endoplasmic reticulum (ER)-resident molecular chaperone glucose
      regulated protein 94 (Grp94) belonging to the Hsp90 family, and purified Grp94
      was phosphorylated by a kinase in cell lysates in an NLS-dependent fashion. The
      100 kDa protein was identified as Grp94 by immunoprecipitation and reconstitution
      experiments. Purification of the NLS-dependent Grp94 kinase by sequential
      biochemical column chromatography steps resulted in isolation of two polypeptides
      with molecular masses of 42 and 27 kDa, which were identified as alpha and beta
      subunit of protein kinase CK2, respectively, by western blotting analysis and
      biochemical characterization. Moreover, effect of an excess amount of GTP and V8
      peptide mapping showed that the NLS-dependent Grp94 kinase in the cell lysate is
      identical with CK2. Surprisingly purified CK2 did phosphorylate Grp94 even
      without the NLS-peptide, suggesting that an additional suppressive factor is
      required for NLS-dependent phosphorylation of Grp94 by CK2. We suggest a possible
      general role for CK2-catalyzed phosphorylation in the regulation of NLS-dependent
      protein nuclear translocation.

PMID- 21739155
TI  - Structural and functional determinants of protein kinase CK2alpha: facts and open
      questions.
AB  - Ser/Thr protein kinase CK2 is involved in several fundamental processes that
      regulate the cell life, such as cell cycle progression, gene expression, cell
      growth, and differentiation and embryogenesis. In various cancers, CK2 shows a
      markedly elevated activity that has been associated with conditions that favor
      the onset of the tumor phenotype. This prompts to numerous studies aimed at the
      identification of compounds that are able to inhibit the catalytic activity of
      this oncogenic kinase, in particular, of ATP-competitive inhibitors. The many
      available crystal structures indicate that this enzyme owns some regions of
      remarkable flexibility which were associated to important functional properties.
      Of particular relevance is the flexibility, unique among protein kinases, of the
      hinge region and the following helix alphaD. This study attempts to unveil the
      structural bases of this characteristic of CK2. We also analyze some
      controversial issues concerning the functional interpretation of structural data
      on maize and human CK2 and try to recognize what is reasonably established and
      what is still unclear about this enzyme. This analysis can be useful also to
      outline some principles at the basis of the development of effective ATP
      competitive CK2 inhibitors.

PMID- 21739156
TI  - Synthetic osteogenic growth peptide promotes differentiation of human bone marrow
      mesenchymal stem cells to osteoblasts via RhoA/ROCK pathway.
AB  - The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide
      that has attracted considerable clinical interest as a bone anabolic agent and
      hematopoietic stimulator. In vitro studies have demonstrated that OGP directly
      regulates the bone marrow mesenchymal stem cells' (BMSCs) differentiation into
      osteoblasts. However, the exact mechanism of this process remains unknown. In the
      present study, we investigated the role of RhoA/ROCK signaling in differentiation
      along this lineage using human BMSCs. OGP treatment increased the mRNA level of
      bone morphogenetic protein-2 and alkaline phosphatase activity after osteogenic
      induction. Analysis of BMSCs induced in the presence of OGP revealed an increase
      in RhoA activity, and phosphorylation of FAK and cofilin. The ROCK-specific
      inhibitors, Y27632, blocked the OGP-induced regulation of BMSC differentiation.
      Taken together, these data suggest that OGP not only acts on BMSCs to stimulate
      osteogenic differentiation, but also in a dose-dependent manner, and this effect
      is mediated via the activation of RhoA/ROCK pathway.

PMID- 21739157
TI  - Serotonergic neurons in the nucleus raphe obscurus contribute to interaction
      between central and peripheral ventilatory responses to hypercapnia.
AB  - Serotonergic (5-HT) neurons in the nucleus raphe obscurus (ROb) are involved in
      the respiratory control network. However, it is not known whether ROb 5-HT
      neurons play a role in the functional interdependence between central and
      peripheral chemoreceptors. Therefore, we investigated the role of ROb 5-HT
      neurons in the ventilatory responses to CO2 and their putative involvement in the
      central-peripheral CO2 chemoreceptor interaction in unanaesthetised rats. We used
      a chemical lesion specific for 5-HT neurons (anti-SERT-SAP) of the ROb in animals
      with the carotid body (CB) intact or removed (CBR). Pulmonary ventilation (V
      (E)), body temperature and the arterial blood gases were measured before, during
      and after a hypercapnic challenge (7% CO2). The lesion of ROb 5-HT neurons alone
      (CB intact) or the lesion of 5-HT neurons of ROb+CBR did not affect baseline V
      (E) during normocapnic condition. Killing ROb 5-HT neurons (CB intact)
      significantly decreased the ventilatory response to hypercapnia (p < 0.05). The
      reduction in CO2 sensitivity was approximately 15%. When ROb 5-HT neurons lesion
      was combined with CBR (anti-SERT-SAP+CBR), the V (E) response to hypercapnia was
      further decreased (-31.2%) compared to the control group. The attenuation of CO2
      sensitivity was approximately 30%, and it was more pronounced than the sum of the
      individual effects of central (ROb lesion; -12.3%) or peripheral (CBR; -5.5%)
      treatments. Our data indicate that ROb 5-HT neurons play an important role in the
      CO2 drive to breathing and may act as an important element in the central
      peripheral chemoreception interaction to CO2 responsiveness.

PMID- 21739158
TI  - Feasibility and effectiveness of inhaled carboplatin in NSCLC patients.
AB  - BACKGROUND: Inhaled chemotherapy is under investigation as an alternative
      therapeutic modality for Non-Small Cell Lung Cancer. METHODS: 60 NSCLC patients
      were randomized into 3 groups in this study. 20/60 patients (group A-control
      group) received I.V. chemotherapy (carboplatin AUC ~ 5.5 D1); 20/60 (group B)
      received 2/3 of I.V. predicted carboplatin dose by I.V. infusion and the rest 1/3
      as aerosol (jet nebulised D1); and 20/60 (group C) received all the predicted
      I.V. dose of carboplatin as aerosol in 3 equally divided fractions D1-3. In all
      patients I.V. docetaxel 100/m(2) was as well administered (D1). Lung functional
      tests were performed in all groups before chemotherapy in the 3rd and 6th cycles.
      RESULTS: Group B had a statistically significant increase in survival compared to
      control group A [275 days (95% CI 249-300) vs. 211 (95% CI 185-236)]. In regard
      to lung functional tests, a statistically significant decline was observed only
      in FEV1 of group C in 6 months compared to the initial measurement. CONCLUSIONS:
      Inhaled carboplatin could be given as an alternative root of pulmonary drug
      delivery in selected patients, but further randomized studies remain to prove
      whether the inhaled chemotherapy is an efficient and safe treatment modality.

PMID- 21739160
TI  - Traditional healing practices among American Muslims: perceptions of community
      leaders in southeast Michigan.
AB  - Despite growing numbers of American Muslims, little empirical work exists on
      their use of traditional healing practices. We explored the types of traditional
      healing practices used by American Muslims in southeast Michigan. Twelve semi
      structured interviews with American Muslim community leaders identified through a
      community-academic steering committee were conducted. Using a framework coding
      structure, a multidisciplinary investigative team identified themes describing
      traditional healing practices. Traditional healing practices can be categorized
      into three domains: Islamic religious text based practices, Islamic worship
      practices, and folk healing practices. Each domain may further contain therapies
      such as spiritual healing, medicinal herbs, mind body therapy, and dietary
      prescriptions. Traditional healing practices are utilized in three capacities of
      care: primary, secondary, and integrative. Our findings demonstrate that American
      Muslims actively utilize traditional healing practices. Healthcare practitioners
      caring for this population should be aware of the potential influence of these
      practices on health behaviors.

PMID- 21739159
TI  - Phylogeography of the red coral (Corallium rubrum): inferences on the
      evolutionary history of a temperate gorgonian.
AB  - The red coral Corallium rubrum (Cnidaria, Octocorallia) is an exploited, long
      lived sessile species from the Mediterranean Sea and the adjacent coastline in
      the Atlantic Ocean. Surveys of genetic variation using microsatellites have shown
      that populations of C. rubrum are characterized by strong differentiation at the
      local scale but a study of the phylogeography of this species was still lacking.
      Here, we used seven polymorphic microsatellite loci, together with sequence data
      from an intron of the elongation factor 1 (EF1) gene, to investigate the genetic
      structure of C. rubrum across its geographical range in the western Mediterranean
      Sea and in the Adriatic Sea. The EF1 sequences were also used to analyse the
      consequences of demographic fluctuations linked with past environmental change.
      Clustering analysis with microsatellite loci highlighted three to seven genetic
      groups with the distinction of North African and Adriatic populations; this
      distinction appeared significant with AMOVA and differentiation tests.
      Microsatellite and EF1 data extended the isolation by distance pattern previously
      observed for this species at the western Mediterranean scale. EF1 sequences
      confirmed the genetic differentiation observed between most samples with
      microsatellites. A statistical parsimony network of EF1 haplotypes provided no
      evidence of high sequence divergence among regions, suggesting no long-term
      isolation. Selective neutrality tests on microsatellites and EF1 were not
      significant but should be interpreted with caution in the case of EF1 because of
      the low sample sizes for this locus. Our results suggest that recent Quaternary
      environmental fluctuations had a limited impact on the genetic structure of C.
      rubrum.

PMID- 21739161
TI  - Bioaccumulation of mercury in muscle tissue of yellowfin tuna, Thunnus albacares,
      of the eastern Pacific Ocean.
AB  - Tuna, like most large pelagic fish, are highly exploited by man, and it is,
      therefore, important to determine mercury (Hg) levels in these species in order
      to establish allowable limits for their consumption and/or contamination levels
      in the environment. In this study, we evaluated Hg accumulation in yellowfin tuna
      (Thunnus albacares) muscle in two different geographic sites of the eastern
      Pacific Ocean. There was a positive association between Hg content and tuna size
      in the equatorial zone (EQZ). Using adjusted sizes, the site of origin was a
      determinant factor in Hg accumulation. Sex, by contrast, did not affect Hg
      levels, suggesting that males and females have similar feeding habits. No Hg
      concentration was over the Hg content thresholds for large marine predators
      adopted by Mexican norms and by North American authorities (1 MUg g(-1) w.w.). Hg
      input due to yellowfin tuna consumption represented from 9.84% to 35.87% in Baja
      California Sur and from 14.78% to 53.87% in EQZ of the provisional tolerable
      weekly intake adopted by the World Health Organization. The target hazard
      quotient for Hg was <1 in each group of the population studied, which indicates
      that consumption of yellowfin tuna is not a threat to human health.

PMID- 21739162
TI  - Concentrations of sodium, potassium, magnesium, and iron in the serum of dairy
      cows with subclinical ketosis.
AB  - Serum concentrations of sodium, potassium, magnesium, and iron were measured in
      dairy cows with subclinical ketosis. Compared with healthy cows, the
      subclinically ketotic cows had significantly higher levels of non-esterified
      fatty acids and beta-hydroxybutirate in serum and significantly lower levels of
      blood glucose (p < 0.01). No significant differences were observed, suggesting
      that the mineral elements measured are not involved in the pathogenesis of
      subclinical ketosis.

PMID- 21739163
TI  - Simultaneous administration of fluoride and selenite regulates proliferation and
      apoptosis in murine osteoblast-like MC3T3-E1 cells by altering osteoprotegerin.
AB  - The receptor activator nuclear factor kappa-B ligand (RANKL) and its decoy
      receptor, osteoprotegerin (OPG), are important for maintaining the balance
      between bone formation and resorption. However, the regulation of microelements
      on these factors remains unclear. In this study, we used murine osteoblast-like
      MC3T3-E1 cells to examine the impact of sodium fluoride (NaF) and/or sodium
      selenite (Na2SeO3) on the OPG/RANKL system. MC3T3-E1 cells were treated with OPG
      or RANKL siRNA (or left untreated), and subsequently divided into a control group
      and five experimental groups, which were exposed to different concentrations of
      NaF and/or Na2SeO3, and subsequently analysed at 24 h. In particular, we examined
      cell viability, OPG and RANKL mRNA and protein expression, caspase-3 activity,
      and the cell cycle of the various cell groups. In summary, our findings suggest
      that the administration of NaF and/or Na2SeO3 affects the expression of OPG in
      osteoblast-like MC3T3-E1 cells, thereby contributing to the proliferation and
      apoptosis induced by the OPG.

PMID- 21739164
TI  - The effect of A(2A) adenosine receptor activation on C-C chemokine receptor 7
      expression in human THP1 macrophages during inflammation.
AB  - C-C chemokine receptor 7 (CCR7) and its chemoattractant agonist CCL21 promote
      cell migration and expression of pro-inflammatory proteins in an atherogenic
      environment. Since A(2A) adenosine receptor activation reduces migration and
      inflammatory effects, we examined its effect on CCR7 expression and migration.
      CCR7 protein expression decreased by about a third in macrophages treated with
      A(2A) receptor agonist CGS 21680 (p = 0.028, n = 7) and was reversed with
      antagonist, although mRNA levels increased twofold (p = 0.001, n = 3).
      Furthermore, macrophages treated with CGS 21680 showed a significant decrease in
      migration (p = 0.0311, n = 7). These results suggest that A(2A) adenosine
      receptor activation not only modulates CCR7 expression in both normal and
      inflammatory environments but also regulates macrophage migration to CCR7
      specific chemoattractants.

PMID- 21739165
TI  - Immunotherapy for tauopathies.
AB  - Pathological tau protein is found in Alzheimer's disease and related tauopathies.
      The protein is hyperphosphorylated and/or mutated which leads to aggregation and
      neurotoxicity. Because cognitive functions correlate well with the degree of tau
      pathology, clearing these aggregates is a promising therapeutic approach. Studies
      pioneered by our laboratory and confirmed by others have shown that both active
      and passive immunizations targeting disease-related tau epitopes successfully
      reduce tau aggregates in vivo and slow or prevent behavioral impairments in mouse
      models of tauopathy. Here, we summarize recent advances in this new field.

PMID- 21739166
TI  - Molecular analysis of thyroid tumors.
AB  - Thyroid cancer is the most common endocrine malignancy, and its incidence is
      rising in the USA and other countries. Papillary and follicular thyroid
      carcinomas are the two most common types of thyroid cancer. Non-overlapping
      genetic alterations, including BRAF and RAS point mutations, and RET/PTC and
      PAX8/PPARgamma rearrangements, are found in more than 70% of papillary and
      follicular thyroid carcinomas. These represent the most common genetic
      alterations in thyroid cancer, as well as molecular markers of diagnostic and
      prognostic significance. The use of these and other emerging molecular markers
      will likely improve the diagnosis of malignancy in thyroid nodules as well as
      facilitate more individualized operative and postoperative management. Herein, we
      provide a brief overview of the common genetic alterations in papillary and
      follicular thyroid carcinoma and discuss the diagnostic and prognostic
      significance thereof.

PMID- 21739167
TI  - How to find and diagnose a CDG due to defective N-glycosylation.

PMID- 21739168
TI  - Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02,
      a phase II trial with measures of treatment delivery.
AB  - Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the
      alphavbeta3 and alphavbeta5 integrins. Preclinical studies demonstrate
      antiangiogenic activity and anti-invasive activity in a number of glioma models.
      This study was designed to evaluate the efficacy and tumor delivery of
      cilengitide in patients with recurrent glioblastoma. Patients with recurrent
      glioblastoma who require a surgical resection for optimal clinical care received
      3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1)
      prior to undergoing tumor resection with corresponding blood samples for plasma
      to tumor comparisons. After recovery from surgery, patients were treated with
      cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). The
      study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for
      efficacy. The 6-month progression free survival rate was 12%. Cilengitide was
      detected in all tumor specimens with higher levels in the group receiving 2000 mg
      dosing while corresponding plasma concentrations were low, often below the lower
      limit of detection. These results confirm drug delivery and possibly retention in
      tumor. This study provides evidence that with established dosing, cilengitide is
      adequately delivered to the tumor, although as a single agent, efficacy in
      recurrent glioblastoma is modest. However, these results demonstrating drug
      delivery to tumor do support continued investigation of this agent as preliminary
      results from recent studies combining cilengitide with cytotoxic therapies are
      promising.

PMID- 21739169
TI  - Prophylactic intrathecal chemotherapy in primary CNS lymphoma.
AB  - The role of prophylactic intrathecal chemotherapy in the treatment of primary
      central nervous system lymphoma remains controversial. We report a retrospective
      single center study of a cohort of 69 patients with primary central nervous
      system lymphoma who had been treated with a regimen that combined high
      intravenous doses of Methotrexate, CCNU, procarbazine and methylprednisolone.
      Before 2000, patients systematically received intrathecal prophylaxis including
      Methotrexate, cytarabine, and hydrocortisone delivered either by intraventricular
      or lumbar injection along with the systemic chemotherapy (group A, n = 39). After
      this date, the procedure was changed and intrathecal chemotherapy was withdrawn
      from the protocol (group B, n = 30). The median age and Karnofsky index were
      comparable in both groups. At the time of analysis, we found no significant
      difference between patients with and without intrathecal prophylaxis in terms of
      objective response rate, patterns of relapse, progression-free survival or
      overall survival. In our study, intrathecal prophylaxis withdrawal from a high
      dose intravenous Methotrexate-based chemotherapy regimen did not influence
      disease control and outcome of primary central nervous system lymphoma. Further
      studies prospectively investigating the role of intrathecal chemoprophylaxis are
      warranted for this disease.

PMID- 21739170
TI  - Kinetics and mechanism of the cutinase-catalyzed transesterification of oils in
      AOT reversed micellar system.
AB  - The kinetics of the enzymatic transesterification between a mixture of
      triglycerides (oils) and methanol for biodiesel production in a bis(2-ethylhexyl)
      sodium sulfosuccinate (AOT)/isooctane reversed micellar system, using recombinant
      cutinase from Fusarium solani pisi as a catalyst, was investigated. In order to
      describe the results that were obtained, a mechanistic scheme was proposed, based
      on the literature and on the experimental data. This scheme includes the
      following reaction steps: the formation of the active enzyme-substrate complex,
      the addition of an alcohol molecule to the complex followed by the separation of
      a molecule of the fatty acid alkyl ester and a glycerol moiety, and release of
      the active enzyme. Enzyme inhibition and deactivation effects due to methanol and
      glycerol were incorporated in the model. This kinetic model was fitted to the
      concentration profiles of the fatty acid methyl esters (the components of
      biodiesel), tri-, di- and monoglycerides, obtained for a 24 h transesterification
      reaction performed in a stirred batch reactor under different reaction conditions
      of enzyme and initial substrates concentration.

PMID- 21739171
TI  - Potential roles for new communication technologies in treatment of addiction.
AB  - Information and communication technologies offer clinicians the opportunity to
      work with patients to manage chronic conditions, including addiction. The early
      research on the efficacy of electronic treatment and support tools is promising.
      Sensors have recently received increased attention as key components of
      electronic treatment and recovery management systems. Although results of the
      research are very promising, concerns at the clinical and policy level must be
      addressed before widespread adoption of these technologies can become practical.
      First, clinicians must adapt their practices to incorporate a continuing flow of
      patient information. Second, payment and regulatory systems must make adjustments
      far beyond what telemedicine and electronic medical records have required. This
      paper examines potential roles of information and communication technologies as
      well as process and regulatory challenges.

PMID- 21739172
TI  - Clinical characteristics of acute mitral regurgitation due to ruptured chordae
      tendineae in infancy-experience at a single institution.
AB  - In infants, acute mitral regurgitation resulting from ruptured chordae tendineae
      is very rare, but often fatal. There are a few case reports, but the
      characteristics and etiology of chordae tendineae rupture have not been
      elucidated. Our aim was to determine the clinical characteristics of idiopathic
      acute mitral regurgitation due to chordal rupture in infancy. A retrospective
      analysis was performed on ten consecutive patients, with a mean onset age of 4.6
      +/- 1.3 months. Despite nonspecific initial symptoms, all patients developed
      respiratory distress and four required resuscitation within a few days (mean, 1.8
      +/- 1.8 days). Chest radiographs showed pulmonary congestion with a normal or
      mildly increased cardiothoracic ratio in all ten patients. Laboratory data and
      electrocardiograms showed nonspecific findings. Echocardiography revealed
      ruptured chordae in all patients; locations were anterior (50%), posterior (20%),
      and both (30%). Surgical intervention was performed within 24 h of admission in
      eight patients (mean, 3.6 +/- 5.1 h). Pathological findings included inflammatory
      cells in six specimens and myxomatous degeneration in two. No bacteria were
      isolated from preoperative blood cultures, pathological tissues, or excised
      tissue cultures. Autoantibody levels were insignificant. Three preoperatively
      resuscitated patients developed neurological sequelae and arrhythmias occurred in
      four after mitral valve replacement. Acute onset and rapid deterioration in
      patients with ruptured chordae tendineae necessitates early surgical intervention
      to improve outcomes. Though the etiology remains unknown, onset is in infants
      approximately 4 months of age, suggesting a definite disease entity.

PMID- 21739173
TI  - X-linked adrenal hypoplasia congenita: a novel DAX1 missense mutation and
      challenges for clinical diagnosis in Africa.
AB  - Adrenal hypoplasia congenita (AHC) is a rare disease. The X-linked form of AHC is
      caused by deletions or mutations in DAX1 gene and has a variable clinical
      presentation. To date, no data on X-linked AHC in central Africa are available.
      Here, we report a Congolese pedigree with several cases of unexplained deaths of
      male infants. A careful analysis of the pedigree of this family lead to the
      recognition of an X-linked inheritance pattern, with subsequent confirmation in a
      female heterozygous carrier of a DAX1 missense mutation c.1274G>T,
      (p.Arg425Ile).The diagnosis of this condition remains challenging in a developing
      country, since the manifestations of AHC overlap with those of the much more
      frequently occurring infections; darkening of the skin is difficult to evaluate
      and there is a lack of access to routine endocrinological testing. The diagnosis
      was eventually made based on the family pedigree, evoking an X-linked inheritance
      pattern. This illustrates the necessity for medical and clinical genetics to be
      part of the curriculum of medical school in developing countries.

PMID- 21739174
TI  - Influence of gravity for optimal head positions in the treatment of head injury
      patients.
AB  - BACKGROUND: Brain edema is a major neurological complication of traumatic brain
      injury (TBI), commonly including a pathologically increased intracranial pressure
      (ICP) associated with poor outcome. In this study, gravitational force is
      suggested to have a significant impact on the pressure of the edema zone in the
      brain tissue and the objective of the study was to investigate the significance
      of head position on edema at the posterior part of the brain using a finite
      element (FE) model. METHODS: A detailed FE model including the meninges, brain
      tissue and a fully connected cerebrospinal fluid (CSF) system was used in this
      study. Brain tissue was modelled as a poroelastic material consisting of an
      elastic solid skeleton composed of neurons and neuroglia, permeated by
      interstitial fluid. The effect of head positions (supine and prone position) due
      to gravity was investigated for a localized brain edema at the posterior part of
      the brain. RESULTS: The water content increment at the edema zone remained nearly
      identical for both positions. However, the interstitial fluid pressure (IFP)
      inside the edema zone decreased around 15% by having the head in a prone position
      compared with a supine position. CONCLUSIONS: The decrease of IFP inside the
      edema zone by changing patient position from supine to prone has the potential to
      alleviate the damage to central nervous system nerves. These observations
      indicate that considering the patient's head position during intensive care and
      at rehabilitation might be of importance to the treatment of edematous regions in
      TBI patients.

PMID- 21739175
TI  - Evaluation of efficacy and biocompatibility of a novel semisynthetic collagen
      matrix as a dural onlay graft in a large animal model.
AB  - BACKGROUND: Semisynthetic collagen matrices are promising duraplasty grafts with
      low risk of cerebrospinal fluid (CSF) fistulas, good tissue integration and minor
      foreign body reaction. The present study investigates the efficacy and
      biocompatibility of a novel semisynthetic bilayered collagen matrix (BCM, B.
      Braun Aesculap) as dural onlay graft for duraplasty. METHODS: Thirty-four pigs
      underwent osteoclastic trepanation, excision of the dura, and placement of a
      cortical defect, followed by duraplasty using BCM, Suturable DuraGenTM (Integra
      Neuroscience), or periosteum. CSF tightness and intraoperative handling of the
      grafts were evaluated. Pigs were sacrificed after 1 and 6 months for histological
      analysis. FINDINGS: BCM and DuraGenTM showed superior handling than periosteum
      with a trend for better adhesion to dura and CSF tightness for BCM. Periosteum,
      which was sutured unlike the synthetic grafts, had the highest intraoperative CSF
      tightness. Duraplasty time with periosteum was significantly higher (14.4 +/- 2.7
      min) compared with BCM (2.8 +/- 0.8 min) or DuraGenTM (3.0 +/- 0.5 min). Tissue
      integration by fibroblast infiltration was observed after 1 month for all
      devices. More adhesions between graft and cortex were observed with DuraGenTM
      compared with BCM and periosteum. No relevant adhesions between leptomeninges and
      BCM were observed and all devices showed comparable lymphocytic reaction of the
      brain. All devices were completely integrated after 6 months. BCM and DuraGenTM
      showed a trend for an enhanced lymphocytic reaction of the brain parenchyma
      compared with periosteum. Implant rejection was not observed. CONCLUSION:
      Semisythetic collagen matrices are an attractive alternative in duraplasty due to
      their easy handling, lower surgical time, and high biocompatibility.

PMID- 21739176
TI  - Identifiability in biobanks: models, measures, and mitigation strategies.
AB  - The collection and sharing of person-specific biospecimens has raised significant
      questions regarding privacy. In particular, the question of identifiability, or
      the degree to which materials stored in biobanks can be linked to the name of the
      individuals from which they were derived, is under scrutiny. The goal of this
      paper is to review the extent to which biospecimens and affiliated data can be
      designated as identifiable. To achieve this goal, we summarize recent research in
      identifiability assessment for DNA sequence data, as well as associated
      demographic and clinical data, shared via biobanks. We demonstrate the
      variability of the degree of risk, the factors that contribute to this variation,
      and potential ways to mitigate and manage such risk. Finally, we discuss the
      policy implications of these findings, particularly as they pertain to biobank
      security and access policies. We situate our review in the context of real data
      sharing scenarios and biorepositories.

PMID- 21739177
TI  - Prevalence of intracranial artery calcification in hemodialysis patients--a case
      control study.
AB  - BACKGROUND: Intracranial artery calcification has been reported to be an
      independent risk factor for ischemic stroke. Also, existence of a positive
      correlation has been reported between the presence of arterial calcification and
      that of ischemic changes in the area supplied by such arteries. While
      intracranial artery calcification has frequently been observed on computed
      tomographic (CT) images of the brain in hemodialysis patients, its prevalence has
      not been reported previously. We investigated our hemodialysis outpatients to
      determine the prevalence of intracranial artery calcification in these patients
      in comparison with that in healthy controls. METHODS: Brain CT examinations were
      performed in 107 patients under maintenance hemodialysis therapy. For comparison,
      43 representatives of the general population who underwent a brain CT examination
      as part of a health checkup were also studied as control subjects. RESULTS:
      Intracranial calcifications were more frequently found among hemodialysis
      patients (87.9%) than among control subjects (53.5%, P = 0.0003), and the
      prevalences of calcification in each of the intracranial arteries in the two
      groups were as follows: vertebral artery (65.5% vs. 25.6%, P = 0.0002), internal
      carotid artery (62.1% vs. 18.6%, P < 0.0001), basilar artery (34.5% vs. 34.9%,
      ns), anterior cerebral artery (0 vs. 2.3%, ns), middle cerebral artery (24.1% vs.
      20.9%, ns), and posterior cerebral artery (5.2% vs. 4.7%, ns). CONCLUSIONS: A
      much higher rate of intracranial artery calcification was observed in
      hemodialysis patients than in the general population, and the most frequently
      involved sites of calcification in these patients were the relatively large
      intracranial arteries.

PMID- 21739178
TI  - Acute kidney injury from pyelonephritis in an elderly man: case report.
AB  - Pyelonephritis is rarely considered in the differential diagnosis of acute kidney
      injury. Acute non-obstructed bacterial pyelonephritis is an infrequent and rarely
      considered cause of rapidly progressive acute kidney injury. A diagnostic
      challenge thus develops as it is difficult to clinically differentiate acute
      kidney injury secondary to ischemic or toxic acute tubular necrosis or papillary
      necrosis versus acute interstitial nephritis secondary to drugs or infectious
      pyelonephritis. We describe a case of acute kidney injury due to suppurative
      pyelonephritis in an elderly immunocompetent man who presented with dysuria,
      vomiting, and fever and later found to have histologic and radiologic proven
      pyelonephritis as the cause of acute kidney injury in the absence of hypotension,
      nephrotoxic agents, non-steroidal analgesics, immunosuppression, urinary tract
      obstruction, or other structural anomalies. The patient was managed with
      antimicrobial therapy, hemodialysis, and a short course of corticosteroids.

PMID- 21739179
TI  - Occurrence of perfluorinated organic acids in the North and Baltic Seas. Part 2:
      distribution in sediments.
AB  - PURPOSE: The distribution of polar perfluorinated compounds (PFCs) in sea water
      of the North and Baltic Seas has been described in part 1 of this study. In part
      2, their occurrence in sediments is described in order to further investigate
      their distribution routes and possible sinks. METHODS: Sediments were extracted
      with methanol and PFCs with chain lengths of C(4) to C(10) analysed by liquid
      chromatography coupled with tandem mass spectrometry. RESULTS: Using the
      developed procedure, PFCs could be determined in sediments from all 15 stations
      which had been sampled. In most samples from the German Bight and western Baltic
      Sea, perfluorooctane sulphonate had the highest concentrations (0.02 to 2.4
      MUg/kg dry weight), followed by perfluorooctanoate at 0.06 to 1.6 MUg/kg dry
      weight. Levels of the other PFCs were five to ten times lower. Concentrations of
      PFCs were similar to those of classical chlorinated hydrocarbons. The spatial
      distribution is strongly influenced by sediment parameters (e.g. total organic
      carbon (TOC)). By normalisation to TOC, regional differences were identified
      between the North and Baltic Sea samples. Sediment/water enrichment ratios
      estimated from field concentrations showed clear dependences on carbon chain
      length and chemical structure. Time trends of PFCs, investigated by analysing a
      sediment core (Skagerrak), differed clearly from those of "classical" pollutants.
      CONCLUSION: Because of the strong influence of sediment parameters and the
      relatively low enrichment of PFCs in sediments, this matrix is less suited for
      investigating spatial distributions. Sediments should be used mainly for
      monitoring temporal trends, preferably using sediment cores.

PMID- 21739180
TI  - VOC amounts in ambient areas of a high-technology science park in Taiwan: their
      reciprocal correlations and impact on inhabitants.
AB  - INTRODUCTION: This study presents bihourly, seasonal, and yearly concentration
      changes in volatile organic compounds (VOCs) in the inlet and effluent water of
      the wastewater treatment plant (WWTP) of a high-technology science park (HTIP) in
      Taiwan, with the VOC amounts at different sites correlated geologically.
      MATERIALS AND METHODS: This research adopted a combination of two systems, solid
      phase microextraction with a gas chromatography/flame ionization detector and an
      assembly of purge and trap coupled with gas chromatography/mass spectrometry, to
      monitor polar and nonpolar VOCs in wastewater. This paper investigated the total
      VOCs, acetone, isopropyl alcohol (IPA), and dimethylsulfide (DMS) concentrations
      in real water samples collected in the ambient area of the HTIP. RESULTS AND
      DISCUSSION: The major contents of VOCs measured in the effluent of the WWTP in
      the HTIP and the surrounding river region were DMS (14-176 ppb), acetone (5-95
      ppb), and IPA (15-316 ppb). In comparison with the total VOCs in the inlet
      wastewater of the WWTP, no corresponding relationship for total VOC concentration
      in the wastewater was observed between the inlet water and effluent water of the
      WWTP. CONCLUSIONS: The peak VOC concentrations appeared in the third season, and
      the correlation of different VOC amounts reflects the production situation of the
      factories. In addition, VOC concentrations at different sites indicate that the
      Ke-Ya River is seemingly an effective channel for transporting wastewater to its
      final destination. The data are good indications for the management of
      environmental pollution near the HTIP.

PMID- 21739181
TI  - Molecular cytogenetic characterization of Philadelphia-negative rearrangements in
      chronic myeloid leukemia patients.
AB  - BACKGROUND: The BCR/ABL gene rearrangement is generated by a reciprocal
      translocation t(9;22)(q34;q11) in chronic myeloid leukemia (CML) patients. In
      most cases, it is cytogenetically visualized by the Philadelphia (Ph) chromosome.
      About 5-10% of CML patients lack cytogenetic evidence of the Ph translocation but
      show BCR/ABL fusion by fluorescence in situ hybridization (FISH) or reverse
      transcriptase-polymerase chain reaction (RT-PCR). Deletions around the
      breakpoints on derivative chromosome 9 including 5'ABL and 3'BCR sequences occur
      in 10-15% of Ph-positive CML patients and are thought to have prognostic
      significance. METHODS: We explored cryptic rearrangements involving chromosomes 9
      and 22 in 3 CML patients with an apparently normal bone marrow karyotypes using
      multiplex RT-PCR and FISH with commercial and home-brew probes. RESULTS: The
      BCR/ABL fusion transcripts were detected by RT-PCR. Using commercial FISH probes,
      the BCR/ABL fusion gene was found on chromosome 22 in two patients and on
      chromosome 9 in one patient. Consecutive FISH assays clarified the mechanism of
      the masked Ph chromosome: in the 3 patients, Ph rearrangement resulted from
      double mechanism consisting in standard translocation t(9;22)(q34;q11) followed
      by a second reversed translocation t(9;22)(q34;q11). One patient achieved major
      cytogenetic response after 6 months of imatinib therapy, and one patient had
      successful bone marrow transplant. CONCLUSIONS: In this study, we have
      characterized three Ph-negative CML patients with cryptic BCR/ABL rearrangement
      generated after an uncommon mechanism involving two sequential translocations and
      confirm that the BCR/ABL hybrid gene may be located on other sites than 22q11. Ph
      negative CML patients with BCR/ABL fusion gene have the same prognosis as
      patients with classical t(9;22).

PMID- 21739182
TI  - Efficacy control of therapy using circulating epithelial tumor cells (CETC) as
      "liquid biopsy": trastuzumab in HER2/neu-positive breast carcinoma.
AB  - PURPOSE: The majority of targeted personalized cancer therapies are effective
      only in part of the patients, and most of these drugs are excessively expensive.
      Therefore, methods are urgently required, which reveal already early during
      treatment, whether the therapy is effective. In the present report, monitoring of
      circulating epithelial tumor cells (CETC) was used as a timely control of
      trastuzumab therapy in patients with HER2/neu-positive breast cancer. METHODS:
      Seventy-nine sequential HER2/neu-positive breast cancer patients, 35 without
      trastuzumab, and 36 treated with 1 year of trastuzumab treatment were included.
      CETC from unseparated white blood cells stained with FITC-anti-EpCAM were
      analyzed repeatedly during chemotherapy and between 2 and 10 times during 1 year
      of maintenance treatment or observation. RESULTS: Patients treated with
      trastuzumab had a better relapse-free survival than patients without trastuzumab
      treatment during the first 2-4 years of follow-up. Decrease in numbers or no
      change versus highly variable numbers or increase (fivefold or more) allowed to
      discriminate highly significantly and clearly (P < 0.0001, hazard ratio 5.5)
      between patients with a low or high risk of relapse. An increase in CETC was
      accompanied by an increasing portion of cells containing a very high number of
      HER2/neu gene amplificates. CONCLUSIONS: Analysis of the behavior of CETC can, in
      the future, contribute to evaluate the efficacy of targeted therapy early during
      the course of the disease, sparing patients unnecessary treatment but also to
      reduce the costs for the health system and to downsize the extent and length of
      clinical studies.

PMID- 21739184
TI  - Voiding urosonography with a second-generation contrast agent versus voiding
      cystourethrography.

PMID- 21739185
TI  - Microfluidic device to study cell transmigration under physiological shear stress
      conditions.
AB  - The development of new drug therapies relies on studies of cell transmigration in
      in vitro systems. Migration has traditionally been studied using two methods, the
      Boyden chamber and a shear flow chamber assay. Though, commonly applied in cell
      transmigration studies, they are far from imitating a natural migration process.
      Here we describe a novel in vitro cell transmigration microfluidic assay, which
      mimicks physiological shear flow conditions in blood vessels. The device was
      designed to incorporate the principles of both the Boyden chamber and the shear
      flow chamber assay, i.e. migration through the membrane under flow conditions.
      The 3D environment of migrating cells is imitated by injecting cell adhesion
      proteins to coat the membrane in the device. We tested the developed device with
      Jurkat cells migration towards medium supplemented with serum, and with chemokine
      induced lymphocytes migration. The applied continuous flow of cell suspension and
      chemoattractant ensures that the concentration gradient is maintained in time and
      space. The cell adhesion proteins used to enhance cell migration in the device
      were fibronectin and VCAM-1. We successfully observed a multistep transmigration
      process by means of the developed microfluidic migration assay. The presented
      device is inexpensive, easy to fabricate and disposable, having a potential to be
      applied in basic research as well as in the drug development process.

PMID- 21739186
TI  - Different regulatory processes control pollen hydration and germination in
      Arabidopsis.
AB  - To elucidate the functional differences in how Arabidopsis stigmas regulate
      pollen hydration and germination, we analyzed receptivity of stigmas, epidermal
      surfaces (leaves, stems of inflorescence bolts, and floral organs), and an
      abiotic surface (cover glass) for pollen hydration and germination. Using 65%
      relative humidity (RH), we found that mature pollen grains were able to hydrate
      and germinate on stigmas at flower developmental stages 9-13, but not on the
      distal end of pistils at stage 8, epidermal surfaces, or glass. Furthermore,
      under 100% RH, pollen grains could hydrate on all tested surfaces, but pollen
      germination was observed only on the young floral organs (stages 9-12) and the
      stigmas at stages 9-13. The distal ends of pistils at stage 8, the epidermal
      surfaces, and the cover glass did not support pollen germination even under 100%
      RH. Our results indicate that pistil factors regulating pollen hydration and
      germination are synthesized at stage 9 when stigmatic papillar cells begin to
      develop. Although pistil factors involved in pollen hydration may only be present
      on the stigma, the factors involved in pollen germination may localize on both
      the stigma and surfaces of unopened floral organs.

PMID- 21739187
TI  - Effects of leg-to-body position on the responses of rat cerebellar and vestibular
      nuclear neurons to labyrinthine stimulation.
AB  - The spatial organization of vestibulospinal (VS) reflexes, elicited by
      labyrinthine signals and related to head motion, depends on the direction of body
      tilt, due to proprioceptive neck afferents acting through the cerebellar anterior
      vermis. The responses of Purkinje cells located within this region to
      labyrinthine stimulation are modulated by the head-to-body position. We
      investigated, in urethane-anesthetized rats, whether a 90 degrees  leg-to-trunk
      displacement modifies the responses of corticocerebellar and vestibular nuclear
      neurons to the labyrinthine input, which would indicate that VS reflexes are
      tuned by the leg-to-trunk position. With this aim, unit activity was recorded
      during "wobble" stimuli that allow evaluating the gain and spatiotemporal
      properties of neuronal responses. The response gain of corticocerebellar units
      showed a significant drop in the leg-rotated position with respect to the control
      one. Following a change in leg position, a proportion of the recorded neurons
      showed significant changes in the direction and phase of the response vector. In
      contrast, vestibular nuclear neurons did not show significant modifications in
      their response gain and direction. Thus, proprioceptive afferents signaling leg
      to-trunk position seem to affect the processing of directional labyrinthine
      signals within the cerebellar cortex.

PMID- 21739188
TI  - Progeroid syndromes: models for stem cell aging?
AB  - Stem cells are responsible for tissue repair and maintenance and it is assumed
      that changes observed in the stem cell compartment with age underlie the
      concomitant decline in tissue function. Studies in murine models have highlighted
      the importance of intrinsic changes occurring in stem cells with age. They have
      also drawn the attention to other factors, such as changes in the local or
      systemic environment as the primary cause of stem cell dysfunction. Whilst
      knowledge in murine models has been advancing rapidly there has been little
      translation of these data to human aging. This is most likely due to the
      difficulties of testing the regenerative capacity of human stem cells in vivo and
      to substantial differences in the aging phenotype within humans. Here we
      summarize evidence to show how progeroid syndromes, integrated with other models,
      can be valuable tools in addressing questions about the role of stem cell aging
      in human degenerative diseases of older age and the molecular pathways involved.

PMID- 21739189
TI  - Pharmacokinetics of miriplatin in experimental dog models of hepatic or renal
      impairment.
AB  - Miriplatin is an anticancer platinum complex for treatment of hepatocellular
      carcinomas by intra-hepatic arterial injection suspended in an iodinated ethyl
      ester of fatty acids from poppy seed oil as a carrier. Effects of liver and
      kidney function on( 14)C-miriplatin pharmacokinetics were assessed using dog
      models of hepatic and renal impairment introduced by thioacetamide exposure and
      7/8 nephrectomy, respectively. Miriplatin was selectively delivered to the liver;
      platinum and radioactive component were gradually released into systemic
      circulation and excreted into urine. Microautoradiographic analysis of liver
      specimens showed( 14)C-miriplatin to be localized in blood vessels and/or
      macrophage-like cells. These features of miriplatin disposition were not affected
      by hepatic impairment. Thus, in clinical settings, hepatic impairment would not
      be expected to affect the intra-hepatic distribution and systemic
      pharmacokinetics of miriplatin. In dogs with renal impairment, although
      inconclusive, plasma concentrations of ultrafilterable platinum and radioactivity
      increased due to reduction in renal clearance.

PMID- 21739190
TI  - Acceleration of in vitro dissolution studies of sustained release dosage form of
      theophylline and in vitro-in vivo evaluations in terms of correlations.
AB  - The aim of the study was to accelerate the dissolution of the sustained release
      dosage forms using both elevated temperature and high rpm rates. Teokap((r)) SR
      200 mg pellets were tested by in vitro sustained and accelerated dissolution
      studies using USP XXIII rotating paddle method. Sustained dissolution studies
      were carried out for 12 h in phosphate buffer at 37 +/- 0.5 degrees C and 50 rpm.
      Accelerated dissolution studies were performed for 48 min in distilled water at
      90 +/- 1 degrees C and 250 rpm. The results obtained from accelerated and
      sustained dissolution studies were correlated using both linear and linear
      kinetic correlation methods by a computer program. While r (2) and maximum error
      between calculated and observed drug release rates were found to be 0.9129 and
      15.9%, respectively, in linear correlation method, these values were observed as
      0.9938 and 3.6%, respectively, in linear kinetic correlation method. In vivo
      plasma concentration data were obtained from six New Zealand rabbits after
      administration of a single dose of Teokap((r)) SR 200 mg pellet. Then, the
      results of in vivo study were evaluated with in vitro accelerated and sustained
      dissolution results by applying them to in vitro-in vivo linear correlations. As
      a result of these correlations, it was shown that the in vitro correlation plots
      were very similar to the plot which was obtained by the in vivo study (f (2) =
      73.81-77.11). This study suggested a way to prevent the loss of time for routine
      dissolution studies of sustained release preparations for quality control
      procedures using in vitro accelerated dissolution tests. The storage and
      quarantine periods of the product in process and process controls in the
      manufactories could be shortened by this method. Calculation of the in vivo
      performance of sustained release dosage forms using the results of the
      accelerated dissolution studies may be counted as another advantage of the
      method.

PMID- 21739191
TI  - Ketamine-midazolam anesthesia for an infant with arthrogryposis multiplex
      congenita: a case with decreased myocardial contractility.

PMID- 21739192
TI  - Backboard insertion in the operating table increases chest compression depth: a
      manikin study.
AB  - The quality of chest compression (CC) is influenced by the surface supporting the
      patient. The present study compared chest compression depth with and without a
      rigid backboard on an operating table with a pressure-distributing mattress. We
      hypothesized that the presence of a backboard would result in an increased depth
      of chest compression on the operating table with a pressure-distributing
      mattress. In a randomized crossover trial, we simulated in-hospital cardiac
      arrest in a Resusci Anne SkillReporter model placed on a standard operating table
      with a 6-cm-thick pressure-distributing mattress. A total of 25 male doctors
      performed CC 30 times, with or without the rigid backboard. Mean chest
      compression depth increased from 4.9 +/- 0.4 to 5.4 +/- 0.3 mm (P < 0.0001) when
      a backboard was present. Mean proportion of compressions >50 mm increased
      significantly with the presence of a backboard (53.6% +/- 32.3%-81.8% +/- 15.0%,
      P < 0.0001). Applying a backboard significantly increased CC depth during
      cardiopulmonary resuscitation of a manikin model on an operating table with a
      pressure-distributing mattress.

PMID- 21739193
TI  - Bioconversion of ovine scotta into lactic acid with pure and mixed cultures of
      lactic acid bacteria.
AB  - Scotta is the main by-product in the making of ricotta cheese. It is widely
      produced in southern Europe and particularly in Italy where it represents a
      serious environmental pollutant due to its high lactose content. With the aim of
      evaluating whether scotta bioconversion into lactic acid can be considered as an
      alternative to its disposal, besides providing it with an added value, here the
      growth, fermentative performances, and lactic acid productions of pure and mixed
      cultures of Lactobacillus casei, Lactobacillus helveticus, and Streptococcus
      thermophilus were evaluated on ovine scotta-based media, without and with the
      addition of nutritional supplements. The outcomes indicate that ovine scotta can
      be utilized for the biotechnological production of lactic acid with yields up to
      92%, comparable to those obtained on cheese-whey. Indeed, the addition of
      nutritional supplements generally improves the fermentative performances of
      lactic acid bacteria leading to about 2 g l(-1) h(-1) of lactic acid. Moreover,
      the use of mixed cultures for scotta bioconversion reduces the need for
      nutritional supplements, with no detrimental effects on the productive parameters
      compared to pure cultures. Finally, by using L. casei and S. thermophilus in pure
      and mixed cultures, up to 99% optically pure L: -lactic acid can be obtained.

PMID- 21739194
TI  - Periodontal disease as a risk factor for adverse pregnancy outcomes: a systematic
      review and meta-analysis of case-control studies.
AB  - Periodontal disease is a highly prevalent group of illnesses of microbial
      etiology, whose consequence is a severe breakdown of tooth-supporting structures.
      A link between periodontal infection and several systemic conditions, among which
      adverse pregnancy outcomes, has been suggested in the recent years. The aim of
      this review based on case-control studies was to evaluate if periodontal disease
      could be considered as a risk factor for preterm birth, low birth-weight and
      preterm low birth-weight. An electronic search (via Pubmed) was performed for
      case-control studies investigating the relationship between periodontal disease
      and adverse pregnancy outcomes. From the initially retrieved 417 articles, 17
      case-control studies, accounting for a total of 10,148 patients, were included in
      the review and in the meta-analysis. The estimated odds ratio was 1.78 (CI 95%:
      1.58, 2.01) for preterm birth, 1.82 (CI 95%: 1.51, 1.20) for low birth-weight and
      3.00 (CI 95%: 1.93, 4.68) for preterm low birth-weight. Despite the results of
      the analysis of pooled data suggested a link between periodontal diseases and
      adverse pregnancy outcomes, the presence of important confounders, whose effect
      could not be addressed, prevents a validation of the meta-analysis outcomes.
      Further more accurate investigations based on individual data analysis could give
      a better insight into the topic of the present review.

PMID- 21739195
TI  - Model-derived dose rates per unit concentration of radon in air in a generic
      plant geometry.
AB  - A model for the derivation of dose rates per unit radon concentration in plants
      was developed in line with the activities of a Task Group of the International
      Commission on Radiological Protection (ICRP), aimed at developing more realistic
      dosimetry for non-human biota. The model considers interception of the unattached
      and attached fractions of the airborne radon daughters by plant stomata,
      diffusion of radon gas through stomata, permeation through the plant's epidermis
      and translocation of deposited activity to plant interior. The endpoint of the
      model is the derivation of dose conversion coefficients relative to radon gas
      concentration at ground level. The model predicts that the main contributor to
      dose is deposition of (214)Po alpha-activity on the plant surface and that
      diffusion of radon daughters through the stomata is of relatively minor
      importance; hence, daily variations have a small effect on total dose.

PMID- 21739196
TI  - MicroRNA signature analysis in colorectal cancer: identification of expression
      profiles in stage II tumors associated with aggressive disease.
AB  - PURPOSE: Colorectal cancer (CRC) is a clinically diverse disease whose molecular
      etiology remains poorly understood. The purpose of this study was to identify
      miRNA expression patterns predictive of CRC tumor status and to investigate
      associations between microRNA (miRNA) expression and clinicopathological
      parameters. METHODS: Expression profiling of 380 miRNAs was performed on 20
      paired stage II tumor and normal tissues. Artificial neural network (ANN)
      analysis was applied to identify miRNAs predictive of tumor status. The
      validation of specific miRNAs was performed on 102 tissue specimens of varying
      stages. RESULTS: Thirty-three miRNAs were identified as differentially expressed
      in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p,
      miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease.
      Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced
      expression of miR-143 (p = 0.016) were associated with aggressive mucinous
      phenotype. Increased expression of miR-10b was also associated with mucinous
      tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b
      expression were observed from T1 to T4 lesions and from stage I to IV disease.
      CONCLUSION: Association of specific miRNAs with clinicopathological features
      indicates their biological relevance and highlights the power of ANN to reliably
      predict clinically relevant miRNA biomarkers, which it is hoped will better
      stratify patients to guide adjuvant therapy.

PMID- 21739197
TI  - Apical-node metastasis in sigmoid colon or rectal cancer: is it a factor that
      indicates a poor prognosis after high ligation?
AB  - PURPOSE: The prognostic significance of apical-node metastasis around the
      inferior mesenteric artery (IMA) remains unclear. We investigated the oncological
      relevance of apical-node metastasis detected after high ligation of the IMA in
      stage III sigmoid colon or rectal cancer. METHODS: Between May 2003 and December
      2007, 229 consecutive patients with stage III sigmoid colon or rectal cancer, who
      had undergone curative resection with high ligation, were analyzed. Cox
      proportional regression model was used to identify the prognostic factors for
      disease-free survival. RESULTS: Thirty-one patients (13.5%) had apical-node
      metastases: 0% with T0-1, 3.8% with T2, 11.5% with T3, and 29.3% with T4 disease
      (p = 0.017). Additionally, the factors related to apical-node metastasis were
      tumor size, number of metastatic lymph nodes, lymph-node ratio, and N-stage.
      Multivariate analysis showed that the lymph-node ratio (odds ratio (OR) = 40.53,
      95% confidence interval (CI) = 8.41-195.22, p < 0.001) was an independent
      prognostic factor for disease-free survival but that apical-node metastasis was
      not a factor that predicted a poor outcome (OR = 1.53, 95% CI = 0.81-2.91, p =
      0.192). Apical-node metastasis was not a prognostic factor for disease-free
      survival on multivariate analysis of the subgroups based on tumor location
      (sigmoid colon cancer: OR = 1.42, 95% CI = 0.42-1.82, p = 0.577; rectal cancer:
      OR = 1.82, 95% CI = 0.82-4.06, p = 0.141). CONCLUSIONS: This study suggests that
      apical-node metastasis is not a poor prognostic factor for stage III sigmoid
      colon or rectal cancer after high ligation.

PMID- 21739198
TI  - [BK virus nephropathy after kidney transplantation].
AB  - JC and BK viruses are strains of the polyomavirus group with pathogenic potential
      in humans. BK is the most frequent pathogenic agent of polyomavirus nephropathy
      (BKVN) in kidney transplant patients, which is only exceptionally caused by JC
      virus. Asymptomatic BK virus infection is often acquired in childhood and the
      virus persists in urothelium and kidneys of healthy individuals, where it can be
      reactivated under immunosuppression. Up to 10% of transplanted kidneys are
      affected by BKVN, while the risk of transplant failure due to BKVN exceeds 50% in
      some publications. In kidney biopsies BKVN leads to tubulointerstitial nephritis,
      which may be difficult to distinguish from acute cellular rejection without
      additional use of immunohistochemistry for a polyomavirus antigen. Typical
      hallmarks of BKVN include cytopathic effects caused by the virus with cell lysis,
      denudation of tubular basement membranes and nuclear inclusion bodies. An early
      diagnosis is essential for transplant survival, making screening of blood and
      urine for BK virus after kidney transplantation part of the standard care of
      renal transplant patients today. In the case of significant viremia or biopsy
      proven BKVN immunosuppression is reduced to allow clearing of the virus.

PMID- 21739199
TI  - Two-body wear of dental porcelain and substructure oxide ceramics.
AB  - The aim of this in vitro study was to investigate the two-body wear of different
      ceramics. Two-body wear tests were performed in a chewing simulator with steatite
      and enamel antagonists, respectively. Specimens were loaded in a pin-on-block
      design with a vertical load of 50 N for 1.2 * 10(5) cycles; (f = 1.6 Hz; lateral
      movement, 1 mm; mouth opening: 2 mm). Human enamel was used as a reference. Three
      zirconia ceramics, three veneering porcelains, two glass-infiltrated and one
      lithium disilicate ceramic were investigated. Veneering and lithium disilicate
      ceramics were glazed before testing. Surface roughness Ra (SP6, Perthen-Feinpruf,
      G) and wear depth were determined using a 3D scanner (Laserscan 3D, Willytec, G).
      SEM (Quanta FEG 400, FEI, USA) pictures of the worn specimens and antagonists
      were made for evaluating wear performance. Veneering porcelain provided wear
      traces between 71.2 and 124.1 MUm (enamel antagonist) and 117.4 and 274.1 MUm
      (steatite). Wear of the steatite antagonists varied between 0.618 and 2.85 mm2.
      No wear was found for zirconia and glass-infiltrated substructure ceramics. Also,
      no wear was found for the corresponding antagonists. Wear of specimens and
      antagonists was strongly material dependent. No visible wear was found on
      zirconia and glass-infiltrated ceramics. Porcelain and lithium disilicate ceramic
      showed a comparable or lower wear than the enamel reference. Antagonist wear was
      found to be lower when specimens were made of substructure oxide ceramics instead
      of veneering porcelain. From the point of wear testing, zirconia may be used for
      the fabrication of fixed dental prosthesis without veneering.

PMID- 21739200
TI  - Consumer participation and organizational development in health care: a
      systematic review.
AB  - OBJECTIVE: To provide an overview of published data on user participation in
      Health Care. BACKGROUND: Active and passive involvement of consumers into agendas
      associated with Health Care is still an exception. Data on the success of user
      participation projects in various areas of Health Care are lacking. DESIGN:
      Systematic literature review using public databases. RESULTS: We identified 467
      studies including five systematic reviews describing various participation
      projects, among them workshops, citizens' panels, focus groups, citizens' juries,
      and consultation meetings. A general trend favoring a specific method was not
      observed. The categorization of evaluable studies according to Health Care area
      (n = 331) yielded the following results: general medicine/preventive medicine (n
      = 5), internal medicine/oncology (n = 132), obstetrics and gynecology (n = 2),
      surgery (n = 1), neurology/psychiatry (n = 2), social medicine (n = 16), health
      worker training (n = 38), and research agenda setting (n = 135). Predefined
      qualitative parameters were extracted from 69/467 (15%) studies. Sixty one of 69
      studies (88%) were retrospective analyses without control groups and without
      outcome assessment. Six studies had outcome assessment, three judged the outcome
      as successful, two as negative, and one multi-project study reported 'very
      successful' project assessments in 24% of the projects. In 18 studies, the level
      of consumer participation was described as 'informed' in 2/18, 'advisory' in
      14/18, and 'decision-making' in 2/18. The following factors associated with
      project success were identified: adequate financing, partnerships with well
      institutionalized consumer organizations, advanced project logistics, small-scale
      projects, and adequate internal and external communication. CONCLUSIONS: Most
      consumer participation projects were performed in research agenda setting,
      internal medicine/oncology, and health worker training. Various methods have been
      used in the projects, the level of consumer participation was low, and the
      success rate of the investigated projects was moderate. Potential factors
      associated with project success and future areas of research are discussed.

PMID- 21739201
TI  - Massive infestation with fur mites (Lynxacarus mustelae) of a stone marten
      (Martes foina) from Tyrol.
AB  - A massive infestation with Lynxacarus mustelae (Megnin, 1885) (Acari, Astigmata,
      Listrophoridae) was diagnosed in a stone marten (Martes foina) from Tyrol,
      Austria. In addition, Ixodes rugicollis and Trichodectes retusus are reported for
      the first time in Austria, and the five species of helminths found (Capillaria
      aerophila, C. mustelorum, C. paranalis, C. plica, Molineus patens) are first
      records in the stone marten in the country.

PMID- 21739202
TI  - Endometriosis and regional lymph node involvement in a rat model.
AB  - OBJECTIVE(S): To establish an experimental bowel endometriosis model in the rat
      and to investigate regional lymph node involvement. STUDY DESIGN: Twenty Sprague
      Dawley rats were subjected to autologous transplantation of endometrial tissue to
      the ileocecum by laparotomy. After two months, endometriotic lesions and
      mesenteric lymph nodes were harvested by repeat laparotomy subjected to
      histologic assessment regarding the histologically verified presence of
      endometriosis in the ileocecum and in mesenteric lymph nodes. RESULT(S): A total
      of 20 rats were subjected to autologous transplantation of endometrial tissue to
      the ileocecum. Ileocecal endometriosis was successfully induced in 19/20 (95%)
      rats. In 18/20 animals, the mesenteric lymph node was identified and resected.
      Regional lymph node involvement by endometriosis was identified in 0/18
      mesenteric lymph nodes. CONCLUSION(S): Endometriosis can be successfully induced
      in a rat model by autologous transplantation of endometrial tissue. In this
      experimental rodent endometriosis model, regional mesenteric lymph node
      involvement by endometriosis was not identified.

PMID- 21739203
TI  - Prognostic significance of HER2/neu expression in gastric cancer.
AB  - BACKGROUND: Gastric cancer is still the most prevalent neoplasia in many
      countries. Therefore, besides the clinicopathological factors known to be
      prognostic markers, new independent parameters are being investigated. There is
      mounting evidence of the role of HER2/neu expression in patients with this type
      of cancer, and it has been solidly correlated to poor outcomes and a more
      aggressive disease. PATIENTS AND METHODS: Fifty gastric cancer tissue specimens
      were examined for the presence of HER2/neu by immunohistochemistry. The
      correlation between HER2/neu expression and patient clinicopathological
      parameters was evaluated and the prognostic significance of HER2/neu expression
      was assessed. RESULTS: HER2/neu membrane staining was detectable in 7 (14.0%)
      cases. The patients with HER2/neu overexpression had worse prognosis after
      surgical therapy compared with those without expression of HER2/neu (p = 0.001,
      Log-rank test). No relationship was found between HER2/neu expression and other
      clinicopathological parameters. CONCLUSIONS: Using immunohistochemistry, our data
      showed that the association between HER2/neu overexpression and patient survival
      provides a good indirect validation for quality of this investigation and it may
      act as a prognostic parameter in gastric cancer.

PMID- 21739204
TI  - In vitro activity of antifungal drugs against Plasmodium falciparum field
      isolates.
AB  - The increasing resistance of the malaria parasite Plasmodium falciparum to
      currently available drugs necessitates a continuous effort to develop new
      antimalarial agents. We therefore aimed to assess the in vitro activity of the
      antifungal drugs clotrimazole, fluconazole, ketoconazole, itraconazole,
      voriconazole, flucytosine, amphotericin B, and caspofungin against field isolates
      of P. falciparum from Lambarene, Gabon. Using the histidin-rich protein 2 (HRP-2)
      assay we determined the drug susceptibility (EC(50), EC(90)) of 16 field isolates
      obtained from outpatients attending the Albert Schweitzer Hospital in Lambarene,
      Gabon. For fluconazole, itraconazole and caspofungin the in vitro growth
      inhibition of these drugs is reported for the first time. Our data indicate that
      clotrimazole, fluconazole, itraconazole and caspofungin show median EC(50) values
      of 3.1 ug/mL, 1.9 ug/mL, 1.1 ug/mL and 1.1 ug/mL respectively. Ketoconazole,
      voriconazole, flucytosine and amphotercin B showed no relevant growth inhibition
      within the range of drug concentrations used in this study.

PMID- 21739205
TI  - Is the systemic inflammatory reaction to surgery responsible for post-operative
      pain after tonsillectomy, and is it "technique-related"?
AB  - AIMS: Investigate the influence of operative technique on post-operative
      morbidity and the systemic inflammatory response after tonsillectomy. In
      addition, our aim was to compare the systemic inflammatory reaction, post
      operative pain severity, and required time before the resumption of normal
      physical activity between two groups of tonsillectomized children and to
      correlate characteristics of the systemic inflammatory reaction to post-operative
      morbidity. PARTICIPANTS AND METHODS: This prospective, randomized, and single
      blind study included 100 children between the ages of 3-16 years and who were
      scheduled for a tonsillectomy at our department for chronic tonsillitis and/or
      respiratory obstruction. The children were randomly assigned into one of two
      groups: either a conventional tonsillectomy with bipolar diathermy coagulation or
      a radiofrequency tonsillectomy procedure; both groups had a 14-day follow-up. We
      investigated the severity and duration of postoperative pain (based on the use of
      analgesics during the postoperative period), the postoperative day that they
      resumed normal physical activity, and the rate of postoperative hemorrhage. In
      order to assess the systemic inflammatory response, serum C-reactive protein
      (CRP) levels were measured before the surgery and seven days after the procedure.
      RESULTS: After the surgery CRP levels increased to a statistically significant
      level (t = -4.7; p < 0.001) in conventional tonsillectomy group. There was a
      statistically significant correlation between increased blood CRP levels after
      the surgery and the level of post-operative analgesic consumption, which was
      based on an increased number of analgesic applications (r = 0.28; p < 0.01) and a
      greater number of days in which analgesics were consumed (r = 0.26; p < 0.01).
      There was also a correlation between increased blood CRP levels and a longer
      required time to resume normal physical activities (r = 0.30; p < 0.01).
      CONCLUSION: Post-operative morbidity after tonsillectomy appears to depend on the
      systemic inflammatory response to surgery. This response is "technique-related,"
      wherein a less-aggressive surgical technique produces a weaker post-operative
      inflammatory response and less post-operative morbidity.

PMID- 21739206
TI  - Brain changes in myasthenia gravis-related hypoxia.

PMID- 21739207
TI  - Atypical "mid-ventricular" Tako-tsubo cardiomyopathy in a patient suffering from
      posttraumatic stress disorder: A case report.
AB  - The syndrome of "left ventricular ballooning" summarizes an acute onset of
      transient extensive akinesia of several segments (apical, mid-ventricular) of the
      left ventricle, without significant lesions on the coronary angiogram,
      accompanied by chest symptoms, electrocardiographic changes, and limited release
      of cardiac markers disproportionate to the extent of akinesia. Initially, the
      vast majority of cases has been reported among Japanese population. Emotional or
      physical stress or other preceding triggering factors might play a key role in
      this reversible form of cardiomyopathy, but the precise etiology remains unknown.
      We describe a case of a 52-year-old woman with posttraumatic stress disorder
      after cerebral bleeding presenting with an atypical form of left ventricular
      ballooning ("midventricular ballooning") syndrome.

PMID- 21739208
TI  - Evaluation of the sustainability of the Public Health Program "Slim without Diet
      (Schlank ohne Diat)".
AB  - BACKGROUND: The prevalence of obesity and associated illnesses is continuously
      rising in industrialized countries. As a preventive measure, the Lower Austria
      Health Insurance Fund, together with the Institute of Social Medicine of the
      Medical University Vienna has launched the weight reduction program "Slim without
      Diet (SWD)". The Program's aim is to change the participants' eating and exercise
      habits. The methodical approach is to enhance the individual's self-control so
      that participants are able to identify, break, and modify false behavior
      patterns. During this project, the data from 4,053 individuals were descriptively
      evaluated by using the statistical program SPSS (Version 15). RESULTS: The
      scientifically recommended target group regarding Body Mass Index and age was
      reached and the weight reduction success rate is comparable to similar programs.
      Follow-up checks of the project carried out 6 and 12 months after the end of the
      intervention phase showed that participants were able to maintain an average
      weight loss of 4.26 kg compared to their weight at program-start. The
      participants who follow the therapy recommendations achieved significantly higher
      weight loss and weight reduction also correlates with the number of attended
      group sessions (p < 0.001). The attendance frequency at the follow-up checks,
      however, shows a decreasing tendency of up to 75 percent. CONCLUSION: The results
      show that there is need to develop new methods to increase motivation and
      compliance of the participants to achieve long-term success. A first trial in
      this direction was to implement an additional module - participants had the
      chance of ongoing contacts after the group sessions have finished. The results
      until now show that a possible participation in the follow-ups is not
      significantly affected by ongoing contacts.

PMID- 21739209
TI  - Compartmental resection for subfascial extremity soft tissue sarcoma and quality
      of life in long-term survivors.
AB  - The surgical management of soft tissue sarcoma has changed over the past years,
      resulting in an interdisciplinary multimodal approach and limb-preserving
      treatment modalities. From 464 consecutive patients with a soft tissue sarcoma
      (STS) of an extremity, a compartmental resection was performed in 82 patients,
      usually for primary subfascial large tumors. Postoperative quality of life was
      evaluated using the EORTC Score C30. In our study population, 52% of STS was
      poorly differentiated, 32% moderately, and 16% well differentiated. Survival
      proved to be dependent on tumor grade and tumor biology, but not on tumor size.
      The overall survival rate was 81.5%, 71.9%, and 58.3% after 2, 3, and 5 years,
      respectively. Leiomyosarcoma (39%) and malignant fibrous histiocytoma (42%) are
      associated with poor 5-year survival rate compared to liposarcoma (82%).
      Metastases were observed in 33% of T1 and 43% of T2 tumors corresponding to 51%
      with G3 tumors, 52% with G2 and 23% with G1 tumors. We found a decreased quality
      of life score in our patients in all dimensions compared to a normal population.
      Despite the elevated risk of a functional deficit, compartmental resection
      reduces the risk of local recurrence comparable to the recurrence rates after the
      most radical surgery limb amputation.

PMID- 21739210
TI  - Recurrent symptomatic hypocalcemia during rifampicin therapy for brucellosis.
AB  - Drug-associated hypocalcemia is rare, but may occur during routinely administered
      drugs. We reported a case of vertebral brucellosis, which developed two
      hypocalcemic episodes associated with hypokalemic alkalosis with two drug
      combinations including rifampicin. Possible underlying mechanisms of hypocalcemia
      were discussed. The patient had carpopedal spasm at both hypocalcemic
      presentations. Laboratory analysis revealed hypocalcemia, hypokalemia, alkalosis
      with hypercalciuria, and low-normal parathormone (PTH) at first and elevated PTH
      at the second admission. The patient improved with cessation of drugs and
      appropriate management of hypocalcemia and hypokalemia with calcium, vitamin D,
      magnesium, and potassium replacement. The underlying mechanism of hypocalcemia in
      this patient seemed to be due to tubular damage resulting with Bartter-like
      syndrome, which is well defined with aminogylcosides. But the recurrence of
      hypocalcemia with an aminoglycoside-free antibiotic combination including
      rifampicin suggests a possible role of rifampicin on hypocalcemia associated
      Bartter-like syndrome that has never been reported before.

PMID- 21739211
TI  - Charcot shoulder caused by Chiari type I malformation with syringomyelia with six
      year follow-up.
AB  - We are presenting a case report of neuropathic arthropathy of the shoulder
      secondary to a syringomyelia and Chiari type I malformation, with detailed
      clinical and radiological findings. Neuropathic joints were first described in
      1868 by Charcot, and subsequently were described in many types of peripheral
      diseases and central neuron diseases. There are many causes of syringomyelia, and
      one of the causes of this disease is a Chiari type I malformation. Subsequently,
      shoulders and elbows are most commonly affected by syringomyelia-induced
      neuropathy. Our patient was observed for six years after being diagnosed with
      neuropathic arthropathy and syringomyelia caused by Chiari and did not show any
      disease progression after their surgery.

PMID- 21739212
TI  - [Attitudes towards age-related rationing of medical supply: results of a cross
      national analysis in Germany and Austria].
AB  - BACKGROUND: Expenditure on health-care is increasing over the last years and the
      demographic shift leads to more elderly patients in the health-care system.
      Debates about the financial situation and solution about this topic are common.
      Direct, as well as hidden, rationing is verified by experts. This article
      discusses the concept of age-dependent prioritization and rationing of health
      care expenditures in a cross-national setting. METHODS: With a standardised
      questionnaire geriatric physicians in Germany and Austria were asked about their
      attitude and experience with health-care expenditures in elderly patients.
      Dimension of medical staff, organising institution and financial resources were
      also evaluated. The sample was tested with t-test, Mann-Whitney-U-test and
      explorative factor analysis. All the data were calculated with PASW 17
      Statistics((r)). RESULTS: From 419 standardised questionnaires 288 forms (60%,
      Germany: 123, Austria: 165) were evaluated. Differences were shown in patient-age
      (Germany: 80.4 y, Austria: 71.8 y), carrying capacity (Germany: 74.8, Austria:
      110.8) and in medical staff as physicians (Germany: 6.8, Austria: 12.7) and
      nursing (Germany: 32.2, Austria: 84.3). In infrastructural basic services and
      normative focusing there was only marginal discrepancy, the public/ecclesiastical
      organising institution was 71% in both countries. Related to the different
      financial systems, there was less cost pressure in taking care of elderly
      patients in Austria. CONCLUSION: Age-dependent rationing was approved, but there
      was also a clear endorsement for making resources available for elderly patients
      in future. The discussion about rationing of health-care expenditures will still
      go on and therefore the impact of ageism has to be evaluated in further studies.

PMID- 21739213
TI  - Multi-element stable isotope analysis of H, C, N and S in hair and nails of
      contemporary human remains.
AB  - This paper presents a comparison of the isotopic ratios of hydrogen, carbon,
      nitrogen and sulphur of three pairings of hair and nail tissue taken from
      contemporary human remains. Our aim was to examine the possibility of a direct
      comparison of isotopic data in hair with that of nail tissue for forensic
      purposes. The results indicate that stable isotope ratios of the elements were
      best comparable between human scalp hair longer than 3 cm and the distal end of
      the nails. There were no distinct variations between finger and toenails. Our
      isotopic data for bulk hair and nail confirmed that hair samples were slightly
      enriched in (13)C but depleted in (15)N compared to nail samples. Furthermore,
      our data reveal that delta(34)S values in nail samples were more variable than in
      hair samples. Direct comparison of the corresponding segments of hair and nail
      samples may be difficult due to individual differences especially for delta(15)N
      and delta(2)H. Hair may have an isotopic composition more consistent with the
      ingested food within a specific time than is provided by nail. It can be
      concluded that once a hair is formed, no further metabolic changes of the
      isotopic pattern should occur. Nevertheless, our data suggest that there was a
      change in isotope ratios particularly for delta(2)H along the hair shaft.
      Interpretation of the isotope data in corresponding segments of hair and nail for
      forensic purposes must consider particular variations, especially for
      chronological considerations.

PMID- 21739214
TI  - Expression profile of carbonic anhydrases in articular cartilage.
AB  - Carbonic anhydrases (CAs), which catalyze the reversible reaction of carbonate
      hydration, are important for cartilage homeostasis. The full spectrum of CA
      activity of all 13 isoenzymes in articular cartilage is unknown. This study
      quantified the mRNA profile of CAs in rat articular cartilage, using quantitative
      polymerase chain reactions. Among the 13 functional CAs, CAs II, III, Vb, IX, XII
      and XIII were significantly expressed at mRNA level by the chondrocytes in
      articular cartilage. To verify these significantly expressed CAs in articular
      cartilage at protein level, immunohistochemistry was performed. While CAs III, Vb
      and XII distributed in the full-thickness of cartilage, including the calcified
      zone of cartilage, CA II was mainly localized in the proliferative zone of
      cartilage. CA IX was limited in the superficial zone of cartilage and CA XIII
      expressed in the superficial and partially mid zone. These results provide a
      framework for understanding individual CAs as well as the integrated CA family in
      cartilage biology, including matrix mineralization.

PMID- 21739215
TI  - The response of foetal annulus fibrosus cells to growth factors: modulation of
      matrix synthesis by TGF-beta1 and IGF-1.
AB  - The annulus fibrosus of the intervertebral disc is a complex radial-ply tissue
      that derives initially from segmental condensations of axial mesenchyme
      surrounding the notochord. These mesenchymal condensations differentiate into the
      early annulus fibrosus during foetal development-their outer part becoming
      fibrous, containing collagen type I; and their inner part cartilaginous,
      containing type II collagen and aggrecan. With post-natal growth and ageing,
      there is a switch from type I to type II collagen and an increase in proteoglycan
      synthesis in the outer annulus. This fibrocartilaginous metaplasia appears to
      occur in response to compressive loading of the tissue as occurs in tendons that
      wrap around bony pulleys, and driven by growth factors, such as TGF-beta. In this
      study, using high-density micromass cultures, we have assessed the response of
      foetal outer annulus cells to growth factor stimulation with TGF-beta1 and IGF-1,
      growth factors known to occur within the developing disc. We qualitatively and
      quantitatively describe the stimulatory effects of these growth factors, both
      alone and in combination, on the synthesis of sulphated glycosaminoglycan, and
      collagen types I and II by annulus cells. We show a potential role for TGF-beta1
      in pushing cells towards a fibrocartilaginous phenotype, with possible
      complementary effects of IGF-1.

PMID- 21739216
TI  - A potential role of calcium in apoptosis and aberrant chromatin forms in porcine
      kidney PK15 cells induced by individual and combined ochratoxin A and citrinin.
AB  - The aim of this study was to establish the involvement of calcium signalling in
      genotoxicity, apoptosis and necrosis evoked by ochratoxin A (OTA) and citrinin
      (CTN) alone or in combination in porcine kidney PK15 cells. Cell proliferation
      test (MTT) and trypan blue assays (24 h) demonstrated that CTN (IC(50) = 73.5 +/-
      1.0, 75.4 +/- 1.4 MUM, respectively) was less toxic than OTA (IC(50) = 14.0 +/-
      2.4, 20.5 +/- 1.0 MUM, respectively). To test their cytotoxic interactions, two
      doses of single OTA (6 and 10 MUM) and CTN (30 and 50 MUM) and their combinations
      were applied. Combined treatment showed additive cytotoxic effects. OTA and CTN
      induced dose-dependent increase in cytosolic calcium level (assessed with Fura-2
      AM). However, combined treatment did not provoke additional increase in calcium
      signal. The rate of apoptosis and necrosis (DAPI-antifade staining) was
      significantly higher after 12 h than 24 h, while the frequencies of micronuclei
      (MNs) and nuclear buds (NBs) were higher after 24 h than 12 h treatment. Combined
      exposure resulted in apoptotic and necrotic synergism, while genotoxic effects of
      OTA + CTN were noted as antagonistic or additive. Co-exposure of cells to calcium
      chelator BAPTA-AM significantly reduced CTN and OTA + CTN-evoked apoptosis.
      Twenty-four hour after co-exposure to BAPTA-AM and a single OTA and CTN, MNs
      significantly decreased while NBs dropped significantly after co-treatment with
      BAPTA-AM and OTA + CTN. In conclusion, disturbance of Ca(2+) homeostasis caused
      by OTA and CTN plays a significant role in cell genotoxicity and death.

PMID- 21739217
TI  - Management of fat accumulation in patients with HIV infection.
AB  - The use of antiretroviral therapies has improved survival in people living with
      HIV to nearly normal rates. However, ongoing low-level HIV replication and
      incomplete immune recovery are associated with a chronic inflammatory stimulus.
      This increases several non-typically AIDS-related complications, including fat
      mass changes and metabolic conditions. Abdominal adiposity occurs as a result of
      complex interactions involving HIV itself, antiretroviral drug-associated
      factors, and several intermediary metabolic alterations and abnormal hormone
      levels. Abdominal adiposity in turn can further the metabolic derangements, and
      increase the risk of diabetes and cardiovascular disease. Abnormal growth hormone
      secretion plays a role in development of the fat depot changes. Effective long
      term interventions to decrease central adiposity are limited but studies using
      growth hormone and especially growth hormone-releasing factor have shown
      encouraging results. Other emerging therapeutic options have been variably
      successful in the short term and the continuing clinical and therapeutic
      challenges will require ongoing investigation.

PMID- 21739218
TI  - Influences of cadmium on fine structure and metabolism of Hypnea musciformis
      (Rhodophyta, Gigartinales) cultivated in vitro.
AB  - The in vitro effect of cadmium on apical segments of Hypnea musciformis was
      examined. Over a period of 7 days, the segments were cultivated with different
      concentrations of cadmium, ranging from 50 to 300 MUM. The samples were processed
      for microscopic and histochemical analysis of growth rates, content of
      photosynthetic pigments, and photosynthetic performance. Cadmium treatments
      increased cell wall thickness and the accumulation of plastoglobuli. Destruction
      of chloroplast internal organization was observed. Compared to controls, algae
      exposed to cadmium showed growth rate reduction, depigmentation, and blending in
      the lateral branches. The content of photosynthetic pigments, including
      chlorophyll a and phycobiliproteins, decreased after exposure to different
      concentrations of cadmium. These results agree with the decreased photosynthetic
      performance and relative electron transport rate observed after exposure of algae
      to cadmium. Taken together, these findings strongly indicate that cadmium
      negatively affects the architecture and metabolism of the carragenophyte H.
      musciformis, thus posing a threat to the economic vitality of this red
      macroalgae.

PMID- 21739219
TI  - CT and MR perfusion can discriminate severe cerebral hypoperfusion from perfusion
      absence: evaluation of different commercial software packages by using digital
      phantoms.
AB  - INTRODUCTION: Computed tomography perfusion (CTP) and magnetic resonance
      perfusion (MRP) are expected to be usable for ancillary tests of brain death by
      detection of complete absence of cerebral perfusion; however, the detection limit
      of hypoperfusion has not been determined. Hence, we examined whether commercial
      software can visualize very low cerebral blood flow (CBF) and cerebral blood
      volume (CBV) by creating and using digital phantoms. METHODS: Digital phantoms
      simulating 0-4% of normal CBF (60 mL/100 g/min) and CBV (4 mL/100 g/min) were
      analyzed by ten software packages of CT and MRI manufacturers. Region-of-interest
      measurements were performed to determine whether there was a significant
      difference between areas of 0% and areas of 1-4% of normal flow. RESULTS: The CTP
      software detected hypoperfusion down to 2-3% in CBF and 2% in CBV, while the MRP
      software detected that of 1-3% in CBF and 1-4% in CBV, although the lower limits
      varied among software packages. CONCLUSION: CTP and MRP can detect the difference
      between profound hypoperfusion of <5% from that of 0% in digital phantoms,
      suggesting their potential efficacy for assessing brain death.

PMID- 21739220
TI  - A tomographic study of the skull base in primary spontaneous cerebrospinal fluid
      leaks.
AB  - INTRODUCTION: This study aims to evaluate the existence of anatomic abnormalities
      in the skull base that could contribute to the origin of primary spontaneous
      cerebrospinal fluid leaks (PSL). METHODS: Twenty PSL patients were compared with
      20 healthy individuals. The following features were measured through an analysis
      of computed tomography scans: the angles of the petrosal bones and skull base in
      both the sagittal and coronal planes; the anteroposterior and mediolateral
      diameters of the anterior skull base, sella, and sphenoid sinus; the depth of the
      olfactory fossa; the pneumatization of the sphenoid sinus; the position of the
      crista galli; and the state of the dorsum sellae. Body mass index (BMI) was
      compared. RESULTS: There were no differences between the two groups with respect
      to the angles and diameters of the anterior cranial fossa and the sphenoid sinus
      or the depth of the olfactory fossa. Pneumatization of the lateral recess of the
      sphenoid sinus was more frequent in the PSL group (55%) than in the control group
      (25%, p = 0.053). The dorsum sellae were eroded in 30% of the PSL patients but
      intact in all healthy subjects. PSL subjects showed higher sellae (1.0 versus 0.8
      cm, p = 0.002). The average BMI of PSL patients was higher than that of the
      control group. CONCLUSION: Global alterations in the skull base of PSL patients
      were not found. The increase in the height of sellae and the erosion of its
      dorsum suggest intracranial hypertension. The higher BMI in the case group
      confirms the relation between obesity and PSL.

PMID- 21739221
TI  - Quantitative multivoxel proton MR spectroscopy study of brain metabolites in
      patients with amnestic mild cognitive impairment: a pilot study.
AB  - INTRODUCTION: The purpose of this study is to investigate brain metabolic changes
      in patients with amnestic mild cognitive impairment (aMCI) using multivoxel
      proton MR spectroscopy ((1)H-MVS). METHODS: Fourteen aMCI patients and fifteen
      healthy control subjects participated in this experiment. All MR measurements
      were acquired using a 1.5-T GE scanner. (1)H-MVS point resolved spectroscopy (2D
      PROBE-CSI PRESS) pulse sequence (TE = 35 ms; TR = 1,500 ms; phase * frequency, 18
      * 18) was used for acquiring MRS data. All data were post-processed using
      Spectroscopy Analysis by General Electric software and linear combination of
      model (LCModel). The absolute concentrations of N-acetylaspartate (NAA), choline
      (Cho), myoinositol (MI), creatine (Cr), and the metabolite ratios of NAA/Cr,
      Cho/Cr, MI/Cr, and NAA/MI were measured bilaterally in the posterior cingulate
      gyrus (PCG), inferior precuneus (Pr), paratrigonal white matter (PWM), dorsal
      thalamus (DT), and lentiform nucleus (LN). RESULTS: Patients with aMCI displayed
      significantly lower NAA levels in the bilateral PCG (p < 0.01), PWM (p < 0.05),
      and left inferior Pr (p < 0.05). The metabolite ratio of NAA/MI was decreased in
      the bilateral PCG (p < 0.01) and PWM (p < 0.05) and in the left DT (p < 0.01).
      NAA/Cr was decreased in the left PCG (p < 0.01), DT (p < 0.05), right PWM (p <
      0.05), and LN (p < 0.05). However, MI/Cr was elevated in the right PCG (p < 0.01)
      and left PWM (p < 0.05). Significantly increased Cho level was also evident in
      the left PWM (p < 0.05). CONCLUSIONS: Our observations of decreased NAA, NAA/Cr,
      and NAA/MI, in parallel with increased Cho and MI/Cr might be characteristic of
      aMCI patients.

PMID- 21739222
TI  - F-18 FDG PET-CT for predicting survival in patients with recurrent glioma: a
      prospective study.
AB  - INTRODUCTION: Recurrent gliomas are usually histologically high grade; either due
      to recurrence of a de novo high-grade primary or anaplastic transformation in
      case of low-grade tumors. Survival in these patients is variable. The objective
      of the present study is to evaluate the role of FDG PET-CT for predicting
      survival in a large group of patients with suspected recurrent glioma. METHODS: A
      total of 81 previously treated histopathologically proven glioma patients; with
      clinical and conventional imaging findings suspicious of recurrence were included
      in this study. All patients underwent FDG PET-CT study. Based on tumor to white
      matter (T/W) and tumor to grey matter (T/G) ratios, all lesions were scored on
      PET-CT (PET scores 0, 1 and 2). Patients were followed up clinically and by
      repeated imaging. Data was censored, if the patient died of disease or at the end
      of the study. Survival analysis was done for each variable employing univariate
      analysis followed by multivariate analysis, using variables found significant on
      univariate analysis. RESULTS: PET score was found to be the most significant
      predictor of survival in univariate and multivariate analysis (p 0.003). Patients
      having PET score 2 had poorer survival compared to both PET score 0 (p 0.001) and
      PET score 1 (p 0.004). Other covariates found to have significant correlation
      with survival were primary treatment modality and clinical symptoms at the time
      of recurrence. CONCLUSION: FDG uptake on PET-CT is a strong predictor of survival
      in patients with suspected recurrent glioma.

PMID- 21739223
TI  - Phytotoxicity of antofine from invasive swallow-worts.
AB  - Pale swallow-wort (Vincetoxicum rossicum) and black swallow-wort (V. nigrum) are
      two emerging invasive plant species in the northeastern United States and
      southeastern Canada that have shown rapid population expansion over the past 20
      years. Using bioassay-guided fractionation, the known phytochemical
      phenanthroindolizidine alkaloid, (-)-antofine, was identified as a potent
      phytotoxin in roots, leaves, and seeds of both swallow-wort species. In seedling
      bioassays, (-)-antofine, at MUM concentrations, resulted in greatly reduced root
      growth of Asclepias tuberosa, A. syriaca, and Apocynum cannabinum, three related,
      native plant species typically found in habitats where large stands of swallow
      wort are present. In contrast, antofine exhibited moderate activity against
      lettuce, and it had little effect on germination and root growth of either black
      or pale swallow-wort. In disk diffusion assays, antifungal activity was observed
      at 10 MUg and 100 MUg, while antibacterial activity was seen only at the higher
      level. Although both swallow-wort species display multiple growth and
      reproductive characteristics that may play an important role in their
      invasiveness, the presence of the highly bioactive phytochemical (-)-antofine in
      root and seed tissues indicates a potential allelopathic role in swallow-worts'
      invasiveness.

PMID- 21739224
TI  - The Portuguese version of the Personal and Social Performance Scale (PSP):
      reliability, validity, and relationship with cognitive measures in hospitalized
      and community schizophrenia patients.
AB  - PURPOSE: Deficits in social functioning are a core feature of schizophrenia and
      are influenced by both symptomatic and neurocognitive variables. In the present
      study we aimed to determine the reliability and validity of the Portuguese
      version of the Personal and Social Performance (PSP) scale, and possible
      correlations with measures of cognitive functioning. METHODS: One-hundred and
      four community and inpatients with schizophrenia were assessed using measures of
      social functioning and symptom severity alongside measures of executive function,
      processing speed, and verbal memory. RESULTS: Convergent validity with the GAF in
      the four domains of the PSP varied from 0.357 to 0.899. Reliability was found to
      be satisfactory, with a Cronbach's alpha coefficient of 0.789. Inter-rater
      reliability in the four domains of the PSP varied from 0.430 to 0.954. Low
      functioning patients (PSP < 70) were older, had longer duration of illness, were
      more symptomatic and had worse cognitive performances, as compared with high
      functioning patients (PSP >= 70). In a regression model, deficits in social
      functioning were strongly predicted both by symptomatic and neurocognitive
      variables; these together accounted for up to 62% of the variance. CONCLUSIONS:
      The present study supports the reliability and validity of the Portuguese
      language version of the PSP and further supports the original measure. The co
      administration of brief cognitive assessments with measures of functioning may
      lead to more focused interventions, possibly improving outcomes in this group.

PMID- 21739225
TI  - Identification and physicians' views of their commonly-used drug information
      sources in Singapore.
AB  - AIM: To examine physicians' use and views of various sources for general drug
      information and to determine the kind of drug-related questions they receive.
      METHOD: An online survey of general practitioners who were Singapore Medical
      Association members was conducted. The survey consisted of questions about the
      physicians' demographics, the drug information source they used most often, their
      opinions on the information from that source, and the types of drug-related
      questions they received from patients. RESULTS: Among the 236 physicians who
      responded to the survey, 58.1% used reference texts most frequently; of these
      respondents, 80.3% used the Monthly Index of Medical Specialties. Only 4.2% most
      often go to pharmacists for drug information. Of the 75 (31.8%) respondents who
      chose online sources, about half used Google while the remainder used specific
      websites. Most respondents rated drug information from reference texts as
      somewhat comprehensive (71.5%) and usually reliable (81.8%). The choice of drug
      information sources was associated with physicians' age, place of practice,
      access to the Internet, and clinical experience (P < 0.05). The types of drug
      related questions that physicians most frequently received were with regards to
      adverse drug reactions (76.3%), drug costs (36.4%), and drug use during pregnancy
      or lactation (34.3%). CONCLUSION: Most physicians in Singapore search for general
      drug information using reference texts and consider them to be comprehensive and
      reliable. Questions pertaining to adverse drug reactions were the drug-related
      questions physicians most frequently receive. It is important for physicians to
      have appropriate drug information references and learn methods with which to
      verify the credibility of drug information obtained from the Internet.
      Pharmacists can also work to improve their role as providers of drug information.

PMID- 21739226
TI  - Will aspirin rescue us from cancer?

PMID- 21739227
TI  - Use and indications of cholestyramine and bile acid sequestrants.
AB  - Cholestyramine is a bile acid sequestrant, like colestipol and colesevelam. These
      molecules are positively charged non-digestible resins that bind to bile acids in
      the intestine to form an insoluble complex, which is excreted in the feces. They
      are used mainly for the treatment of primary hypercholesterolemia and
      hypercholesterolemia associated with mild hypertriglyceridemia, in patients not
      responding to dietary treatment as well as a second line-treatment for pruritus
      associated with cholestatic disease, in patients with incomplete biliary
      obstruction. Several data indicate that modulation of bile acid homeostasis has a
      good clinical effect in managing diabetes mellitus and the diarrhea from bile
      acid malabsorption. In this review, we present the "in label" use and indication
      for these compounds, revisiting the other clinical applications that may benefit
      from the use of bile acid sequestrants in the near future.

PMID- 21739228
TI  - Is telemetry useful in evaluating chest pain patients in an observation unit?
AB  - Since the development of coronary care units (CCUs), telemetry has rapidly become
      the standard of care in evaluating patients with suspected acute coronary
      syndromes, regardless of the probability for ischemia. However, there is no data
      to support this practice. Our objective was to evaluate the utility of routine
      cardiac monitoring in a chest pain observation unit. We prospectively studied the
      utility of routine cardiac monitoring in 249 consecutive patients admitted to an
      observation unit in an academic Emergency Department over a 6-month period. All
      the patients presented with chest pain thought to be cardiac ischemia.
      Observation included serial cardiac enzymes, ECG cardiac monitoring, and exercise
      testing in a designated chest pain observation unit. These patients were
      determined to be at low risk for an acute coronary event by two criteria: first,
      the symptoms had resolved by the time of observation unit admission, and second,
      the initial ECG was normal, unchanged or non-diagnostic for acute ischemia.
      Adverse outcomes included cardiac arrest, hospital admission secondary to cardiac
      dysrhythmia, or alteration in the patient's medical therapy upon discharge from
      the observation unit, secondary to cardiac dysrhythmia. There were 249 patients
      included with a median age of 52 with 60% women. Fifteen percent of the patients
      were, subsequently, admitted to the hospital for further evaluation of ischemia
      based on enzyme, ECG, and exercise testing results. One patient with known Tachy
      Brady syndrome was noted to have 1.5-2 s pauses while sleeping, and discharged
      with instructions to hold beta blocker therapy pending results of a continuous
      loop recorder. Of the remaining 248 patients, no patient suffered a cardiac
      arrest, no patient was admitted to the hospital secondary to cardiac dysrhythmia,
      and no alteration in a patient's medical therapy was made secondary to cardiac
      dysrhythmia. No patient returned to the Emergency Department within 72 h with
      cardiac arrest, acute dysrhythmia or acute myocardial infarction. Although
      telemetry may be the standard of care in evaluating the patients with suspected
      acute coronary syndromes, regardless of the probability of an acute ischemic
      syndrome, in those patients with a normal or non diagnostic ECG and resolved
      symptoms, routine cardiac monitoring is unnecessary.

PMID- 21739229
TI  - Cardiac amyloidosis: the heart of the matter.
AB  - Amyloidosis comprises a unique group of diseases that share in common the
      extracellular deposition of insoluble fibrillar proteins in organs and tissue
      including the heart. Cardiac amyloidosis could be primary a part of systemic
      acquired amyloidosis, or a result of heredofamilial amyloidosis. Although the
      infiltration of the heart from different types of amyloid results in restrictive
      cardiomyopathy that manifests with refractory congestive heart failure and
      conduction abnormalities, unequivocal identification of the deposited
      amyloidogenic protein is mandatory in order to avoid misdiagnosis and
      inappropriate treatment. Recent developments in imaging techniques and
      extracardiac tissue biopsy have minimized the need for invasive endomyocardial
      biopsy for amyloidosis. Despite advances in treatment, the prognosis of a patient
      with amyloidosis is still poor and depends upon the underlying disease, and the
      type and degree of dysfunction of the involved organs. Thus, early diagnosis is
      mandatory because patients with advanced disease are usually too ill for
      intensive therapy. This review outlines current approaches to diagnosis,
      assessment of disease severity, and treatment of cardiac amyloidosis.

PMID- 21739230
TI  - Post-transcriptional regulation of mu-opioid receptor: role of the RNA-binding
      proteins heterogeneous nuclear ribonucleoprotein H1 and F.
AB  - Classical opioids have been historically used for the treatment of pain and are
      among the most widely used drugs for both acute severe pain and long-term pain.
      Morphine and endogenous mu-opioid peptides exert their pharmacological actions
      mainly through the mu-opioid receptor (MOR). However, the expression of opioid
      receptor (OR) proteins is controlled by extensive transcriptional and post
      transcriptional processing. Previously, the 5'-untranslated region (UTR) of the
      mouse MOR was found to be important for post-transcriptional regulation of the
      MOR gene in neuronal cells. To identify proteins binding to the 5'-UTR as
      potential regulators of the mouse MOR gene, affinity column chromatography using
      5'-UTR-specific RNA oligonucleotides was performed using neuroblastoma NS20Y
      cells. Chromatography was followed by two-dimensional gel electrophoresis and
      MALDI-TOF mass spectrometry. We identified two heterogeneous ribonucleoproteins
      (hnRNPs) that bound to RNA sequences of interest: hnRNP H1 and hnRNP F. Binding
      of these proteins to the RNA region was M4-region sequence-specific as confirmed
      by Western-blot analysis and RNA supershift assay. Furthermore, a cotransfection
      study showed that the presence of hnRNP H1 and F resulted in repressed expression
      of the mouse MOR. Our data suggest that hnRNP H1 and F can function as repressors
      of MOR translation dependent on the M4 (-75 to -71 bp upstream of ATG) sequences.
      We demonstrate for the first time a role of hnRNPs as post-transcriptional
      repressors in MOR gene regulation.

PMID- 21739231
TI  - Four-and-a-half LIM domains protein 2 (FHL2) is associated with the development
      of craniofacial musculature in the teleost fish Sparus aurata.
AB  - Four-and-a-half LIM domains protein 2 (FHL2) is involved in major cellular
      mechanisms such as regulation of gene transcription and cytoskeleton modulation,
      participating in physiological control of cardiogenesis and osteogenesis.
      Knowledge on underlying mechanisms is, however, limited. We present here new data
      on FHL2 protein and its role during vertebrate development using a marine teleost
      fish, the gilthead seabream (Sparus aurata L.). In silico comparison of
      vertebrate protein sequences and prediction of LIM domain three-dimensional
      structure revealed a high degree of conservation, suggesting a conserved function
      throughout evolution. Determination of sites and levels of FHL2 gene expression
      in seabream indicated a central role for FHL2 in the development of heart and
      craniofacial musculature, and a potential role in tissue calcification. Our data
      confirmed the key role of FHL2 protein during vertebrate development and gave new
      insights into its particular involvement in craniofacial muscle development and
      specificity for slow fibers.

PMID- 21739233
TI  - Damage to the vascular structures in inguinal hernia specimens.
AB  - BACKGROUND: Few scientific reports to date describe the histological modification
      of structures outlining a hernia opening. This article is focused on the
      identification of the pathological changes in vascular structures in tissues
      excised from cadavers with inguinal hernia. A deeper comprehension of this topic
      could lead to essential improvements in the detection of hernia genesis.
      MATERIALS AND METHODS: Different kinds of hernia, including indirect, direct and
      mixed, were identified in 30 autopsied subjects. Tissue samples were resected for
      histological study from abdominal wall structures close to the hernia opening.
      Histological examination focused on the detection of structural changes in
      arteries and veins. The results were compared with tissue specimens excised from
      equivalent sites of the inguinal area in a control group of 15 fresh cadavers
      without hernia. RESULTS: Significant modification of vascular structures were
      identified in the tissue specimens examined. The veins demonstrated parietal
      fibrosis, perivascular edema and vascular dilation due to congestion and stasis.
      The arterial structures detected showed thickening of the media due to medial
      hyperplasia, ranging from luminal sub-occlusion to a manifest artery occlusion.
      These findings are present independent of hernia type in cadavers with inguinal
      hernia. These pathological changes were lacking in the control group of cadavers
      without hernia. CONCLUSIONS: The notable changes in vascular structures described
      in the report could be the result of a steady compressive effect exerted by the
      abdominal viscera in the inguinal area. These pathological changes could
      represent one of the factors involved in the weakening of the inguinal region
      leading to hernia protrusion.

PMID- 21739232
TI  - Protein profiling of genomic instability in endometrial cancer.
AB  - DNA aneuploidy has been identified as a prognostic factor in the majority of
      epithelial malignancies. We aimed at identifying ploidy-associated protein
      expression in endometrial cancer of different prognostic subgroups. Comparison of
      gel electrophoresis-based protein expression patterns between normal endometrium
      (n = 5), diploid (n = 7), and aneuploid (n = 7) endometrial carcinoma detected
      121 ploidy-associated protein forms, 42 differentially expressed between normal
      endometrium and diploid endometrioid carcinomas, 37 between diploid and aneuploid
      endometrioid carcinomas, and 41 between diploid endometrioid and aneuploid
      uterine papillary serous cancer. Proteins were identified by mass spectrometry
      and evaluated by Ingenuity Pathway Analysis. Targets were confirmed by liquid
      chromatography/mass spectrometry. Mass spectrometry identified 41 distinct
      polypeptides and pathway analysis resulted in high-ranked networks with vimentin
      and Nf-kappaB as central nodes. These results identify ploidy-associated protein
      expression differences that overrule histopathology-associated expression
      differences and emphasize particular protein networks in genomic stability of
      endometrial cancer.

PMID- 21739234
TI  - Roles of matrix metalloproteinases in the etiology of inguinal hernia.
AB  - INTRODUCTION: The fascia transversalis is accepted as one of the anatomical
      structures that can prevent hernia formation. Degradation of collagen within the
      fascia transversalis is one of the known reasons for the development of inguinal
      hernia. In the present study, we investigated the roles of matrix
      metalloproteinases (MMPs), specifically MMP-1, MMP-2, and MMP-9 in the etiology
      of inguinal hernia. MATERIALS AND METHODS: This prospective study included 60
      inguinal hernia patients: 30 patients had indirect inguinal hernia and 30
      patients had direct inguinal hernia. An additional 30 patients operated for
      reasons other than hernia in the inguinal canal were included as a control group.
      All patients underwent operations at Istanbul Training and Research Hospital
      between 1 June 2009 and 1 December 2009. Tissue specimens were taken from the
      fascia transversalis from patient and control groups during the operation, and
      MMP-1, MMP-2, MMP-9 values were investigated using immunohistochemical methods.
      RESULTS: Significantly higher values of MMP-1, MMP-2, MMP-9, were found in
      inguinal hernia cases than in the control group (P = 0.0001, P = 0.007, P =
      0.021, respectively). CONCLUSION: Increased MMP-1, MMP-2, MMP-9 values play a
      role in the etiology of inguinal hernia. Since weakening may also occur in other
      tissues in addition to the floor of inguinal canal in inguinal hernia patients,
      the association of arterial aneurisms and connective tissue diseases should also
      be investigated in these patients.

PMID- 21739235
TI  - Leonardo da Vinci's Vitruvian Man: a renaissance for inguinal hernias.

PMID- 21739236
TI  - New mesh shape and improved implantation procedure to simplify and standardize
      open ventral hernia repair: a preliminary report.
AB  - INTRODUCTION: Issues in ventral hernia repair are represented by the need for
      mesh fixation and how to assure a sufficient mesh overlap of the defect. Aiming
      to resolve these problems, this study describes a modified technique for ventral
      and incisional hernia repair based upon a newly developed mesh with a special
      design. This new type of implant allows broader coverage of the abdominal wall
      and results in tension- and fixation-free repair. MATERIALS AND METHODS: A unique
      geometrically shaped mesh consisting of a large central body and radiating arms
      was used to repair ventral or incisional hernia. The mesh was intended not to be
      point-fixated. The friction of the straps passing through the tissues was
      hypothesized to be adequate to maintain the mesh firmly fastened in the abdominal
      wall, ensuring a wide coverage far from the hernia border. The newly designed
      mesh was placed in the preperitoneal sublay in 22 patients with ventral or
      incisional hernia. All straps were passed laterally through the transverse and
      oblique muscles. In all patients, a defect overlap of at least 8-12 cm was
      achieved. RESULTS: In a midterm follow-up of 18-24 (mean 22) months, three
      seromas and one infection occurred, which were successfully managed without mesh
      removal. No hematoma, chronic pain, or recurrence has been reported to date.
      CONCLUSIONS: The described arm system of the implant allowed for a much smaller
      incision and eliminated the complicated maneuvers associated with suturing the
      mesh. The fixation arms seemed to have ensured the mesh stayed orientated in all
      patients. A very wide lateral mesh placement was accomplished, assuring
      sufficient defect overlap when shrinkage occurs.

PMID- 21739237
TI  - Random local temporal structure of category fluency responses.
AB  - The Category Fluency Test (CFT) provides a sensitive measurement of cognitive
      capabilities in humans related to retrieval from semantic memory. In particular,
      it is widely used to assess progress of cognitive impairment in patients with
      dementia. Previous research shows that, in the first approximation, the intensity
      of tested individuals' responses within a standard 60-s test period decays
      exponentially with time, with faster decay rates for more cognitively impaired
      patients. Such decay rate can then be viewed as a global (macro) diagnostic
      parameter of each test. In the present paper we focus on the statistical
      properties of the properly de-trended time intervals between consecutive
      responses (inter-call times) in the Category Fluency Test. In a sense, those
      properties reflect the local (micro) structure of the response generation
      process. We find that a good approximation for the distribution of the de-trended
      inter-call times is provided by the Weibull Distribution, a probability
      distribution that appears naturally in this context as a distribution of a
      minimum of independent random quantities and is the standard tool in industrial
      reliability theory. This insight leads us to a new interpretation of the concept
      of "navigating a semantic space" via patient responses.

PMID- 21739239
TI  - Effects of intraguild predators on nest-site selection by prey.
AB  - Nest-site selection involves tradeoffs between the risk of predation (on females
      and/or nests) and nest-site quality (microenvironment), and consequently suitable
      nesting sites are often in limited supply. Interactions with "classical"
      predators (e.g., those not competing for shared resources) can strongly influence
      nest-site selection, but whether intraguild predation also influences this
      behavior is unknown. We tested whether risk of predation from an intraguild
      predator [the diurnal scincid lizard Eutropis (Mabuya) longicaudata] influences
      nest-site selection by its prey (the nocturnal gecko Gekko hokouensis) on Orchid
      Island, Taiwan. These two species putatively compete for shared resources,
      including invertebrate prey and nesting microhabitat, but the larger E.
      longicaudata also predates G. hokouensis (but not its hard-shelled eggs). Both
      species nested within a concrete wall containing a series of drainage holes that
      have either one ("closed-in") or two openings ("open"). In allopatry, E.
      longicaudata preferred to nest within holes that were plugged by debris (thereby
      protecting eggs from water intrusion), whereas G. hokouensis selected holes that
      were open at both ends (facilitating escape from predators). When we
      experimentally excluded E. longicaudata from its preferred nesting area, G.
      hokouensis not only nested in higher abundances, but also modified its nest-site
      selection, such that communal nesting was more prevalent and both open and closed
      in holes were used equally. Egg viability was unaffected by the choice of hole
      type, but was reduced slightly (by 7%) in the predator exclusion area (presumably
      due to higher local incubation temperatures). Our field experiment demonstrates
      that intraguild predators can directly influence the nest density of prey by
      altering maternal nest-site selection behavior, even when the predator and prey
      are active at different times of day and the eggs are not at risk of predation.

PMID- 21739238
TI  - MicroRNAs in brain tumors : a new diagnostic and therapeutic perspective?
AB  - MicroRNAs (miRNAs, miRs) are small, non-coding RNA molecules that regulate gene
      expression posttranscriptionally. Although discovered only recently in the early
      1990s, this relatively new group of molecules has already been proven to play an
      essential role in the regulation of many physiological and, most importantly,
      pathological processes such as cancer. A large number of miRNAs has been found to
      be involved in the pathogenesis of various human malignancies, and expression of
      miRNAs has been demonstrated to correlate with clinic and outcome. In tumors of
      the brain, however, the investigations on the role of miRNAs are still in its
      infancy, and most publications refer to the most common primary brain tumor, the
      glioma (mostly glioblastoma). But despite the fact that there is only limited
      data available so far, these first results are very promising and implicate that
      miRNAs might open a new perspective for diagnostics and treatment of this
      disease. With this review article, we aim to provide a short overview of miRNA
      biogenesis, function and regulation in general. Thereafter, the clinical relevant
      data about miRNAs in the two most common primary malignant brain tumors in adults
      (glioblastomas) and children (medulloblastomas) will be summarized, and their
      potential impact on diagnostics and treatment will be highlighted.

PMID- 21739240
TI  - Modified-policosanol does not reduce plasma lipoproteins in hyperlipidemic
      patients when used alone or in combination with statin therapy.
AB  - Policosanol is a poorly absorbed nutritional supplement used primarily for
      cholesterol management. Findings from previous trials evaluating the effects of
      policosanol are mixed with early data reporting positive lipid effects while more
      recent studies indicate negligible efficacy. We hypothesized that re-formulating
      policosanol would result in an improvement in major lipoproteins and possibly
      provide some explanation for previously conflicting trial data. Our primary
      objectives were to assess the efficacy and safety of modified-policosanol (MP) on
      the major lipoproteins among hyperlipidemic subjects receiving background statin
      therapy or as monotherapy. This 8-week clinical trial consisted of 3 arms.
      Subjects receiving chronic statin therapy (N = 36) were randomized in a double
      blind design to MP 20 mg daily or placebo. In the third arm, subjects not
      receiving statin therapy (N = 18) were assigned open-label MP 20 mg daily. The
      utilization of MP when added to background statin therapy or as monotherapy
      resulted in no significant changes in major lipoproteins (all p > 0.05). The MP
      therapy was well tolerated with no major adverse events reported. Consistent with
      recent clinical trial data, MP demonstrated an excellent safety profile but
      produced no significant effects on major lipoproteins when used as monotherapy or
      when given with concomitant statin therapy.

PMID- 21739241
TI  - Trans-18:1 and CLA isomers in rumen and duodenal digesta of bulls fed n-3 and n-6
      PUFA-based diets.
AB  - The aim of the study was to investigate the effect of n-6 PUFA (maize
      silage/grass silage, soybean meal and soybean oil, control) and n-3 PUFA (grass
      silage, rapeseed cake and rapeseed oil, experiment) based diets on the occurrence
      of rumen- and duodenal digesta trans-C18:1 and CLA isomers of German Simmental
      bulls. The results based on rumen and duodenal digesta samples immediately taken
      from the bulls just after slaughter. The diet affected the occurrence of
      individual trans-C18:1 and CLA isomers in the rumen and duodenal digesta in
      different ways. The isomer trans-11,cis-13 CLA was detected as the most abundant
      isomer in the rumen of n-3 PUFA based diet fed bulls compared to n-6 PUFA based
      diet fed bulls. The trans-7,cis-9 CLA isomer was not detected in the rumen
      samples of bulls fed both diets, however abundant trans-7,cis-9 CLA was
      identified and quantified in the duodenum digesta. Both the concentration of the
      sum of trans-18:1 fatty acids and individual isomers in the rumen were not
      affected by the diet, except trans-16-18:1. The concentration of trans-16-18:1
      was significantly decreased in the rumen of n-3 PUFA supplemented-fed bulls
      compared to n-6 PUFA supplemented-fed bulls.

PMID- 21739242
TI  - trans-trans Conjugated linoleic acid enriched soybean oil reduces fatty liver and
      lowers serum cholesterol in obese zucker rats.
AB  - Conjugated linoleic acid (CLA) is a collection of octadecadienoic fatty acids
      that have been shown to possess numerous health benefits. The CLA used in our
      study was produced by the photoisomerization of soybean oil and consists of about
      20% CLA; this CLA consists of 75% trans-trans (a mixture of t8,t10; t9,t11;
      t10,t12) isomers. This method could be readily used to increase the CLA content
      of all soybean oil used as a food ingredient. The objective of this study was to
      determine the effects of trans-trans CLA-rich soy oil, fed as a dietary
      supplement, on body composition, dyslipidemia, hepatic steatosis, and markers of
      glucose control and liver function of obese fa/fa Zucker rats. The trans-trans
      CLA-rich soy oil lowered the serum cholesterol and low density lipoprotein
      cholesterol levels by 41 and 50%, respectively, when compared to obese controls.
      Trans-trans CLA-rich soy oil supplementation also lowered the liver lipid content
      significantly (P < 0.05) with a concomitant decrease in the liver weight in the
      obese rats. In addition, glycated hemoglobin values were improved in the group
      receiving CLA-enriched soybean oil in comparison to the obese control. PPAR-gamma
      expression in white adipose tissue was unchanged. In conclusion, trans-trans CLA
      rich soy oil was effective in lowering total liver lipids and serum cholesterol.

PMID- 21739243
TI  - Differential expression of the glucose transporters in mouse gustatory papillae.
AB  - Taste receptors and their downstream signaling molecules are activated by sugars
      and sweeteners in the gut and participate in the regulation of glucose transport
      into enterocytes. The glucose transporter families GLUT and SGLT are responsible
      for the absorption of glucose, GLUT4 and SGLT1 being expressed preferentially in
      T1R3-positive taste cells. However, the expression patterns of the other glucose
      transporters in mouse gustatory tissues have not yet been elucidated. Therefore,
      we have examined the expression patterns of the glucose transporters (GLUT1-4 and
      SGLT1-3) in mouse gustatory tissues. Reverse transcription/polymerase chain
      reaction assays have revealed that GLUT1, 3, and 4 and SGLT1 mRNAs are expressed
      in the circumvallate papillae. Immunohistochemical analysis has shown that SGLT1
      is expressed in a subset of the epithelial cells: from the basal cell layer to
      the prickle cell layer and in intragemmal and extragemmal epithelium cells in the
      circumvallate, foliate, and fungiform papillae. GLUT1, GLUT3, and GLUT4 are
      expressed in the prickle cell layers and/or basal cell layers in these papillae.
      Moreover, GLUT1, but not GLUT3 or GLUT4, is expressed in a subset of intragemmal
      and extragemmal epithelium cells in these papillae. Double-labeling experiments
      have demonstrated that GLUT1-positive taste bud cells coexpress gustducin and
      inositol 1,4,5-triphosphate receptor type III. These results suggest that SGLT1
      and GLUT1 play a role in glucose-sensing and/or transport in mouse taste buds.

PMID- 21739244
TI  - Expression of TrkB and BDNF in human cochlea-an immunohistochemical study.
AB  - Surgical human cochlear specimens were obtained during the removal of large
      posterior cranial fossa meningioma by a transcochlear approach in which the
      cochlea was removed for maximal exposure of the tumor and protection of important
      structures, such as the brainstem, cranial nerves, and pivotal blood vessels. The
      cochlear tissue was fixed and cryo-sectioned for tyrosine kinase receptor B
      (TrkB) and brain-derived neurotrophic factor (BDNF) immunohistochemistry. TrkB
      receptor protein was expressed in both neuronal somata and the processes of human
      spiral ganglion neurons (SGNs). In the human organ of Corti, TrkB
      immunoreactivity was mainly present in nerve fibers underneath outer hair cells.
      BDNF expression was found neither in the organ of Corti nor in the spiral
      ganglion of human cochlea. For antibody specificity and for control and
      comparative purposes, TrkB immunocytochemistry was performed in primary cultures
      of cochlear neuron/glia from adult guinea pig. Confocal laser scanning microscopy
      showed that TrkB was homogeneously distributed in the cytoplasm of both neuronal
      somata and axons. Knowledge of the expression of TrkB receptor in human cochlea
      should help to determine the target structures for neuron preservation in hearing
      impaired patients. Our results indicate that the regeneration of SGNs under
      pathological conditions can be enhanced with BDNF/TrkB-based pharmaceutical or
      genetic strategies.

PMID- 21739245
TI  - Morphologic evaluation of the thoracic vertebrae for safe free-hand pedicle screw
      placement in adolescent idiopathic scoliosis: a CT-based anatomical study.
AB  - OBJECTIVE: To evaluate the morphologic characteristics of the thoracic pedicle
      with regard to safe free-hand thoracic pedicle screw placement, based on multi
      planar reconstruction CT images. METHODS: Thirty adolescent idiopathic scoliosis
      (AIS) patients who had undergone posterior corrective surgery for major thoracic
      curve were included in this study. Reconstructed CT axial images at each thoracic
      vertebra were used to measure: (1) the shortest distance from an entry point to
      the ventral cortex of the lamina (critical distance), and (2) the distance from
      the entry point to the tangent of the spinal canal at the medial wall of the
      pedicle (safe distance). The critical length was defined as the distance between
      the critical distance and the safe distance. The distance from the entry point to
      the medial wall breach site (breach distance) was measured on post-operative CT
      images. RESULTS: The mean critical distance was 9.3 +/- 1.1 mm. The critical
      distance of vertebrae from different levels was relatively constant, between 8.1
      and 10.1 mm. The mean safe distance was 15.2 +/- 1.3 mm. The safe distance of
      vertebrae from different levels was also relatively constant, between 14.5 and 16
      mm. The mean critical length was 5.9 +/- 1.0 mm. The critical length of vertebrae
      between T3 and T12 was relatively constant, ranging from 5 to 6.5 mm. The mean
      breach distance was 12.3 +/- 1.3 mm and the each breach always recognized between
      the critical distance and the safe distance. CONCLUSIONS: The risk of pedicle
      medial wall perforation increases as the pedicle probe advances beyond the
      critical distance of 8-10 mm from the entry point, while it decreases entering
      into the safe distance at 14.5-16 mm. These parameters were relatively constant
      even in the most rotated vertebrae at T9 or those with the narrowest pedicle at
      T7 or T4.

PMID- 21739246
TI  - Persistent trigeminal artery and its variants on MR angiography.
AB  - INTRODUCTION: A persistent trigeminal artery (PTA) is the most common carotid
      vertebrobasilar anastomosis. A cerebellar artery that arises from the
      precavernous segment of the internal carotid artery (ICA) without connecting to
      the basilar artery is regarded as a PTA variant. Our study aimed to determine the
      incidence of PTA and its variants and classify them based on magnetic resonance
      (MR) angiography. METHODS: We retrospectively reviewed cranial images of 3,626
      patients who underwent MR angiography in our institution from April 1, 2007
      through December 31, 2009. We ultimately reviewed and analyzed images of 3,491
      patients (2,066 men, 1,425 women) after excluding 135 with unilateral or
      bilateral ICA occlusion or suboptimal image quality. RESULTS: We found 12 cases
      of PTA (7 men, 5 women; right 4, left 8; incidence; 0.34%) and 6 of PTA variants
      (3 men, 3 women; right 3, left 3; incidence; 0.17%). 11 of the 12 PTAs were
      lateral type; 1 was medial. In two of the lateral-type cases, the superior
      cerebellar artery (SCA) arose from the PTA. Among the six variants, the anterior
      inferior cerebellar artery (AICA) arose in five and the posterior inferior
      cerebellar artery (PICA), in one. CONCLUSIONS: On MR angiography, the incidence
      of PTA was 0.34% and of PTA variants, 0.17%. Left PTA was twice as frequent as
      right PTA, but with no statistical significance. Medial-type PTA was extremely
      rare. AICA arose in most PTA variants. Rarely, a lateral-type PTA gave rise to
      the cerebellar artery.

PMID- 21739247
TI  - Is there any relation between distal parameters of the femur and its height and
      width?
AB  - The purpose of this study was to reveal the association whether the distal
      morphometry of femur had a relation with femur height or width. Sixty-six adult
      (35 right and 31 left) dry femurs from Caucasians were used in this study.
      Computed tomography (CT) imaging was applied to obtain measurement values of the
      femur. Femur height (413.29 +/- 28.40 mm) and width (29.86 +/- 2.72 mm) were all
      checked one by one to determine the correlation with the parameters obtained.
      Both values exposed high rates of correlation with height (26 +/- 2.34 mm) and
      width (20.85 +/- 2.76 mm) of femur notch; also, measures of epicondylar,
      bicondylar and condylar diameters of femur were obtained. Measures were checked
      if there was a correlation with femur height and width. Differences displayed in
      distal morphometry of femur according to race and sex are due to other
      morphometric measures of femur rather than race and sex. We believe that
      displaying the high rates of correlation of distal morphometry of femur with
      femur height and width will be the factor which determines the selection and
      production of prosthesis among the long or short individuals of folks.

PMID- 21739248
TI  - 3,5-diiodo-L-thyronine increases FoF1-ATP synthase activity and cardiolipin level
      in liver mitochondria of hypothyroid rats.
AB  - Short-term effects of 3,5-L-diiodothyronine (T(2)) administration to hypothyroid
      rats on F(o)F(1)-ATP synthase activity were investigated in liver mitochondria.
      One hour after T(2) injection, state 4 and state 3 respiration rates were
      noticeably stimulated in mitochondria subsequently isolated. F(o)F(1)-ATP
      synthase activity, which was reduced in mitochondria from hypothyroid rats as
      compared to mitochondria from euthyroid rats, was significantly increased by T(2)
      administration in both the ATP-synthesis and hydrolysis direction. No change in
      beta-subunit mRNA accumulation and protein amount of the alpha-beta subunit of
      F(o)F(1)-ATP synthase was found, ruling out a T(2) genomic effect. In T(2)
      treated rats, changes in the composition of mitochondrial phospholipids were
      observed, cardiolipin (CL) showing the greatest alteration. In mitochondria
      isolated from hypothyroid rats the decrease in the amount of CL was accompanied
      by an increase in the level of peroxidised CL. T(2) administration to hypothyroid
      rats enhanced the level of CL and decreased the amount of peroxidised CL in
      subsequently isolated mitochondria, tending to restore the CL value to the
      euthyroid level. Minor T(2)-induced changes in mitochondrial fatty acid
      composition were detected. Overall, the enhanced F(o)F(1)-ATP synthase activity
      observed following injection of T(2) to hypothyroid rats may be ascribed, at
      least in part, to an increased level of mitochondrial CL associated with
      decreased peroxidation of CL.

PMID- 21739249
TI  - Dairy milk fat augments paclitaxel therapy to suppress tumour metastasis in mice,
      and protects against the side-effects of chemotherapy.
AB  - Milk fat is a natural product containing essential nutrients as well as fatty
      acids and other food factors with reported anti-cancer potential. Here bovine
      milk fat was tested for its ability to inhibit the growth of breast and colon
      cancers and their metastasis to the lung and liver; either alone or in
      combination with the chemotherapeutic agent paclitaxel. A diet containing 5%
      typical anhydrous milk fat (representing ~70% of the total dietary fat component)
      fed to Balb/c mice delayed the appearance of subcutaneous 4T1 breast and CT26
      colon cancer tumours and inhibited their metastasis to the lung and liver, when
      compared to the control diet containing soybean oil as the only fat component. It
      augmented the inhibitory effects of paclitaxel on tumour growth and metastasis,
      and reduced the microvessel density of tumours. It displayed no apparent organ
      toxicity, but instead was beneficial for well-being of tumour-bearing mice by
      maintaining gastrocnemius muscle and epididymal adipose tissue that were
      otherwise depleted by cachexia. The milk fat diet ameliorated gut damage caused
      by paclitaxel in non-tumour-bearing mice, as evidenced by retention of jejunal
      morphology, villi length and intestinal gamma-glutamyl transpeptidase activity,
      and inhibition of crypt apoptosis. It prevented loss of red and white blood cells
      due to both cancer-mediated immunosuppression and the cytotoxic effects of
      chemotherapy. The present study warrants the use of milk fat as an adjuvant to
      inhibit tumour metastasis during cancer chemotherapy, and to spare patients from
      the debilitating side-effects of cytotoxic drugs.

PMID- 21739250
TI  - Diversity of arbuscular mycorrhizal fungi associated with plants growing in fly
      ash pond and their potential role in ecological restoration.
AB  - Root colonization and diversity of arbuscular mycorrhizal fungi (AMF) were
      analyzed in plants growing in fly ash pond. Eight species could be separated
      morphologically, while phylogenetic analyses after PCR amplification of the ITS
      region followed by RFLP and sequencing revealed seven different AM fungal
      sequence types. Phylogenetic analysis showed that these sequences cluster into
      four discrete groups, belonging to the genus Glomus and Archaeospora. Inoculation
      of plants with spores of AM fungal consortia (Glomus etunicatum, Glomus
      heterogama, Glomus maculosum, Glomus magnicaule, Glomus multicaule, Glomus rosea,
      Scutellospora heterogama, and Scutellospora nigra) along with colonized root
      pieces increased the growth (84.9%), chlorophyll (54%), and total P content
      (44.3%) of Eucalyptus tereticornis seedlings grown on fly ash compared to non
      inoculated seedlings. The growth improvement was the consequence of increased P
      nutrition and decreased Al, Fe, Zn, and Cu accumulations. These observations
      suggested that the inoculation of tree seedlings with stress adapted AM fungi aid
      in the reclamation of fly ash ponds.

PMID- 21739251
TI  - Survey of Wolbachia and its phage WO in the Uzifly Exorista sorbillans (Diptera:
      Tachinidae).
AB  - Wolbachia are cytoplasmically inherited alpha-proteobacteria well known for
      inducing a variety of reproductive abnormalities in the diverse arthropod hosts
      they infect. Despite their obligate intracellular lifestyle which usually
      protects bacteria from phage infection, Wolbachia harbor a widespread temperate
      phage called WO. Evidences of horizontal phage transfers indicate that this phage
      could promote genetic exchanges between strains leading to evolutionary changes
      in the genomes of Wolbachia, and could be involved in the phenotypes these
      bacteria induced. In this study, we report the survey of Wolbachia and WO phage
      infections in 20 populations of the Uzifly Exorista sorbillans, a tachinid
      endoparasite of silkworm Bombyx mori, collected from different geographic regions
      of India. Previous studies demonstrated that Wolbachia is associated with
      positive reproductive fitness effects in this species. Polymerase chain reaction
      using the ftsZ gene encoding for a Wolbachia cell division protein and the orf7
      capsid protein gene of the phage showed that all flies checked were infected by
      Wolbachia and its phage WO. Phylogenetic analyses based on the Wolbachia surface
      protein gene revealed 100% of double infections by the arthropod supergroups A
      and B. These results can serve as a valuable basis for understanding the
      evolution of Wolbachia bacteria and may provide information about the dynamics of
      Wolbachia-host associations. This knowledge could be exploited for the use of
      Wolbachia for effective control strategies of the Uzifly, a serious menace of the
      silkworm B. mori.

PMID- 21739252
TI  - Molecular characterization of fecal microbiota in patients with viral diarrhea.
AB  - The study provides molecular analyses of fecal microbiota of diarrhea patients
      infected with four different types of viruses. Fecal specimens from 52 patients
      with viral diarrhea (13 each of adenovirus, norovirus, rotavirus, and astrovirus)
      and six healthy individuals were collected and etiological viral agent was
      confirmed by enzyme immunoassay and specific PCR. To assess the changes in
      microbial diversity in patients with viral diarrhea, DNA from stool were
      extracted and characterized by PCR-denaturing gradient gel electrophoresis (DGGE)
      with universal primers specific for the V3 region of 16S rRNA gene. The strongest
      bands of the DGGE profiling were excised and sequenced to identify the dominant
      groups. Bacteroides vulgatus, Bifidobacterium, and Lactobacillus genera were also
      enumerated by real time PCR. The results revealed that bacterial diversity and
      similarity in feces from viral diarrhea groups were significantly lower (mean H'/
      H'(max) 0.89-0.94, 29-43, respectively) as compared with those of healthy
      individuals (mean H'/ H'(max) 1.36, 59, respectively). Sequencing of dominant
      bands affirmed that diarrhea groups were mainly comprised of phylum Firmicutes,
      such as genera Enterococcus, Peptostreptococcaceae incertae sedi, Streptococcus,
      Weissella, and Clostridium, and opportunistically pathogenic genus Shigella,
      while dominant group in healthy individuals was phylum Bacteroidetes. Copy number
      of Bacteroides vulgatus, Bifidobacterium, and Lactobacillus genera was also
      reduced significantly in viral diarrhea groups as compared to healthy group. It
      is concluded that opportunistic pathogens increases, while other species of
      commensal microbiota decrease significantly in the viral diarrhea patients and
      dysbacteriosis is dependent on type of virus infection.

PMID- 21739253
TI  - Preliminary in vitro insights into the use of natural fungal pathogens of leaf
      cutting ants as biocontrol agents.
AB  - Leaf-cutting ants are one of the main herbivores of the Neotropics, where they
      represent an important agricultural pest. These ants are particularly difficult
      to control because of the complex network of microbial symbionts. Leaf-cutting
      ants have traditionally been controlled through pesticide application, but there
      is a need for alternative, more environmentally friendly, control methods such as
      biological control. Potential promising biocontrol candidates include the
      microfungi Escovopsis spp. (anamorphic Hypocreales), which are specialized
      pathogens of the fungi the ants cultivate for food. These pathogens are
      suppressed through ant behaviors and ant-associated antibiotic-producing
      Actinobacteria. In order to be an effective biocontrol agent, Escovopsis has to
      overcome these defenses. Here, we evaluate, using microbial in vitro assays,
      whether defenses in the ant-cultivated fungus strain (Leucoagaricus sp.) and
      Actinobacteria from the ant pest Acromyrmex lundii have the potential to limit
      the use of Escovopsis in biocontrol. We also explore, for the first time,
      possible synergistic biocontrol between Escovopsis and the entomopathogenic
      fungus Lecanicillium lecanii. All strains of Escovopsis proved to overgrow A.
      lundii cultivar in less than 7 days, with the Escovopsis strain isolated from a
      different leaf-cutting ant species being the most efficient. Escovopsis
      challenged with a Streptomyces strain isolated from A. lundii did not exhibit
      significant growth inhibition. Both results are encouraging for the use of
      Escovopsis as a biocontrol agent. Although we found that L. lecanii can suppress
      the growth of the cultivar, it also had a negative impact on Escovopsis, making
      the success of simultaneous use of these two fungi for biocontrol of A. lundii
      questionable.

PMID- 21739254
TI  - The electron transfer complex between nitrous oxide reductase and its electron
      donors.
AB  - Identifying redox partners and the interaction surfaces is crucial for fully
      understanding electron flow in a respiratory chain. In this study, we focused on
      the interaction of nitrous oxide reductase (N(2)OR), which catalyzes the final
      step in bacterial denitrification, with its physiological electron donor, either
      a c-type cytochrome or a type 1 copper protein. The comparison between the
      interaction of N(2)OR from three different microorganisms, Pseudomonas nautica,
      Paracoccus denitrificans, and Achromobacter cycloclastes, with their
      physiological electron donors was performed through the analysis of the primary
      sequence alignment, electrostatic surface, and molecular docking simulations,
      using the bimolecular complex generation with global evaluation and ranking
      algorithm. The docking results were analyzed taking into account the experimental
      data, since the interaction is suggested to have either a hydrophobic nature, in
      the case of P. nautica N(2)OR, or an electrostatic nature, in the case of P.
      denitrificans N(2)OR and A. cycloclastes N(2)OR. A set of well-conserved residues
      on the N(2)OR surface were identified as being part of the electron transfer
      pathway from the redox partner to N(2)OR (Ala495, Asp519, Val524, His566 and
      Leu568 numbered according to the P. nautica N(2)OR sequence). Moreover, we built
      a model for Wolinella succinogenes N(2)OR, an enzyme that has an additional c
      type-heme-containing domain. The structures of the N(2)OR domain and the c-type
      heme-containing domain were modeled and the full-length structure was obtained by
      molecular docking simulation of these two domains. The orientation of the c-type
      heme-containing domain relative to the N(2)OR domain is similar to that found in
      the other electron transfer complexes.

PMID- 21739255
TI  - Ru binding to RNA following treatment with the antimetastatic prodrug NAMI-A in
      Saccharomyces cerevisiae and in vitro.
AB  - [ImH][trans-Ru(III)Cl(4)(DMSO)(Im)] (where DMSO is dimethyl sulfoxide and Im is
      imidazole) (NAMI-A) is an antimetastatic prodrug currently in phase II clinical
      trials. The mechanisms of action of this and related Ru-based anticancer agents
      are not well understood, but several cellular targets have been suggested.
      Although Ru has been observed to bind to DNA following in vitro NAMI-A exposure,
      little is known about Ru-DNA interactions in vivo and even less is known about
      how this or related metallodrugs might influence cellular RNA. In this study, Ru
      accumulation in cellular RNA was measured following treatment of Saccharomyces
      cerevisiae with NAMI-A. Drug-dependent growth and cell viability indicate
      relatively high tolerance, with approximately 40% cell death occurring at 6 h for
      450 MUM NAMI-A. Significant dose-dependent accumulation of Ru in cellular RNA was
      observed by inductively coupled plasma mass spectrometry measurements on RNA
      extracted from yeast treated with NAMI-A. In vitro, binding of Ru species to drug
      treated model DNA and RNA oligonucleotides at pH 6.0 and 7.4 was characterized by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in
      the presence and absence of the reductant ascorbate. The extent of Ru-nucleotide
      interactions increases slightly with lower pH and significantly in the presence
      of ascorbate, with differences in observed species distribution. Taken together,
      these studies demonstrate the accumulation of aquated and reduced derivatives of
      NAMI-A on RNA in vitro and in cellulo, and enhanced binding with nucleic acid
      targets in a tumorlike acidic, reducing environment. To our knowledge, this is
      also the first study to characterize NAMI-A treatment of S. cerevisiae, a
      genetically tractable model organism.

PMID- 21739256
TI  - A theory and a model to understand glioblastoma development both in the bulk and
      in the microinfiltrated brain parenchyma.
AB  - The prognosis of patients affected by glioblastoma remains dismal despite many
      efforts have been devoted worldwide in research and therapeutic strategies.
      Reasons of our failure include the fact that the patient harboring a glioblastoma
      always has two problems inside the brain, the bulk tumor and the parenchyma
      microinfiltrated; the other reason is that the tumor is able to grow dynamically
      adapting to the mutated conditions of its growth microenvironment. This paper
      tries to give an interpretation to the dynamic process of the tumor growth, from
      the beginning to the end of its natural history, dividing it in three phases, one
      pre-hypoxia and two post-hypoxia, and these are then correlated with the types of
      cancer stem cells (CSCs) involved. Furthermore, the paper proposes an original
      animal model to follow glioblastoma development in only one generation of mice,
      both in the bulk and in the brain parenchyma.

PMID- 21739257
TI  - Distribution and 16S rDNA sequences of Argas monachus (Acari: Argasidae), a soft
      tick parasite of Myiopsitta monachus (Aves: Psittacidae).
AB  - Specimens of Argas monachus Keirans et al. were collected from Myiopsitta
      monachus nests in 42 localities in Argentina and Paraguay from 2006 to 2010. A
      list of localities where this tick has been found is presented. 16S rDNA
      sequences of specimens of A. monachus from different localities were compared to
      confirm whether they belong to the same specific taxon. Argas monachus is present
      in the phytogeographic provinces of Chaco, Espinal, and Monte, but not in the
      Pampa (all from de Chaco Domain) where the host is well distributed. No
      differences were found among 16S rDNA sequences of geographically distant
      specimens.

PMID- 21739258
TI  - [Comparable disorder of the body schema in patients with complex regional pain
      syndrome (CRPS) and phantom pain].
AB  - In patients with complex regional pain syndrome (CRPS) a disruption of the body
      schema has been shown in an altered cortical representation of the hand and in
      delayed reaction times (RT) in the hand laterality recognition task. However, the
      role of attentional processes or the effect of isolated limb laterality training
      has not yet been clarified. The performance of healthy subjects (n = 38), CRPS
      patients (n = 12) and phantom limb pain (PLP) patients (n = 12) in a test battery
      of attentional performance (TAP) and in a limb laterality recognition task was
      compared and the effect of limb laterality training in CRPS patients and healthy
      subjects evaluated. The RTs of both CRPS and PLP patients were significantly
      slower than those of healthy subjects despite normal TAP values. The CRPS and PLP
      patients showed bilaterally delayed RTs. Through training RTs improved
      significantly but the RTs of CRPS patients remained slower than those of healthy
      subjects. In this study an equal disruption of the body schema was found in both
      CRPS and PLP patients which cannot be accounted for by attentional processes. For
      CRPS patients this disorder cannot be fully reversed by isolated limb laterality
      recognition training.

PMID- 21739259
TI  - Low-level laser therapy (LLLT) in human progressive-intensity running: effects on
      exercise performance, skeletal muscle status, and oxidative stress.
AB  - The aim of this work was to evaluate the effects of low-level laser therapy
      (LLLT) on exercise performance, oxidative stress, and muscle status in humans. A
      randomized double-blind placebo-controlled crossover trial was performed with 22
      untrained male volunteers. LLLT (810 nm, 200 mW, 30 J in each site, 30 s of
      irradiation in each site) using a multi-diode cluster (with five spots - 6 J from
      each spot) at 12 sites of each lower limb (six in quadriceps, four in hamstrings,
      and two in gastrocnemius) was performed 5 min before a standardized progressive
      intensity running protocol on a motor-drive treadmill until exhaustion. We
      analyzed exercise performance (VO(2 max), time to exhaustion, aerobic threshold
      and anaerobic threshold), levels of oxidative damage to lipids and proteins, the
      activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase
      (CAT), and the markers of muscle damage creatine kinase (CK) and lactate
      dehydrogenase (LDH). Compared to placebo, active LLLT significantly increased
      exercise performance (VO(2 max) p = 0.01; time to exhaustion, p = 0.04) without
      changing the aerobic and anaerobic thresholds. LLLT also decreased post-exercise
      lipid (p = 0.0001) and protein (p = 0.0230) damages, as well as the activities of
      SOD (p = 0.0034), CK (p = 0.0001) and LDH (p = 0.0001) enzymes. LLLT application
      was not able to modulate CAT activity. The use of LLLT before progressive
      intensity running exercise increases exercise performance, decreases exercise
      induced oxidative stress and muscle damage, suggesting that the modulation of the
      redox system by LLLT could be related to the delay in skeletal muscle fatigue
      observed after the use of LLLT.

PMID- 21739260
TI  - Effects of the Lexington LaserComb on hair regrowth in the C3H/HeJ mouse model of
      alopecia areata.
AB  - Alopecia areata (AA) is a common autoimmune disease that presents with non
      scarring alopecia. It is characterized by intra- or peri-follicular lymphocytic
      infiltrates composed of CD4+ and CD8+ T-cells on histology. To this day, few
      treatments are effective for AA. Here we present findings of using a low-level
      laser comb to alleviate the symptoms of AA in a C3H/HeJ mouse model for AA.
      Fourteen C3H/HeJ mice with induced AA were used in this study. Two were killed to
      confirm AA through histology. The remaining 12 mice were randomized into two
      groups; group I received HairMax LaserComb (wavelength: 655 nm, beam diameter <5
      mm; divergence 57 mrad; nine lasers) for 20 s daily, three times per week for a
      total of 6 weeks; group II was treated similarly, except that the laser was
      turned off (sham-treated). After 6 weeks of LaserComb treatment, hair regrowth
      was observed in all the mice in group I (laser-treated) but none in group II
      (sham-treated). On histology, increased number of anagen hair follicles was
      observed in laser-treated mice. On the other hand, sham-treated mice demonstrated
      hair follicles in the telogen phase with no hair shaft. LaserComb seems to be an
      effective and convenient device for the treatment of AA in the C3H/HeJ mouse
      model. Human studies are required to determine the efficacy and safety of this
      device for AA therapy.

PMID- 21739261
TI  - Oculocutaneous albinism type 3 (OCA3): analysis of two novel mutations in TYRP1
      gene in two Chinese patients.
AB  - Oculocutaneous albinism (OCA) is a genetic disease characterized by the reduction
      or deficiency of melanin in eyes, skin, and hair. OCA exhibits genetic
      heterogeneity. Presently, there are four types of OCA named as OCA1, OCA2, OCA3,
      and OCA4. OCA3 is more common in African born blacks but rarely found in other
      ethnic populations. Our recent genotyping of patients with OCA of Chinese descent
      has identified two patients who were not OCA1, OCA2, or OCA4. Examination and
      analysis of the TYRP1 gene identified them to be having OCA3. PCR and DNA
      sequencing analysis found that the mutant TYPR1 alleles were present in each of
      the two patients, c.780-791del/c.1067G>A (p.R356Q) and c.625G>TT
      (p.G209LfsX1)/c.643C>T (p.H215Y). The c.780-791del and c.1067G>A mutations have
      been already reported. However, the c.625G>TT and c.643C>T mutations have not
      been previously reported and were found to be maternal and paternal mutations,
      respectively. Moreover, population screening and bioinformatic analysis were
      carried out to determine the effects of these two mutations which revealed that
      both the mutation were pathogenic. Based on the similar mild phenotype of these
      two patients, we suggest that OCA3 might be prevalent within the Chinese
      population.

PMID- 21739262
TI  - Clinical study on the prevention of post-ERCP pancreatitis by pancreatic duct
      stenting.
AB  - Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is
      one of the most common and serious complications of ERCP, which has become a
      major concern for digestive endoscopists. In the present study, we examine
      whether pancreatic duct stenting can reduce the incidence of PEP. Forty patients
      who underwent an ERCP in our hospital were selected according to their risk
      factors for PEP. They were randomly divided into two groups: (1) 20 subjects
      received a pancreatic duct stenting after ERCP to prevent pancreatitis (stent
      group, S); and (2) the other 20 subjects did not receive pancreatic duct stenting
      after ERCP (non-stent group, NS). Urine and serum amylase, and serum lipase were
      determined after the operation; symptoms of abdominal pain were monitored; cost
      of hospitalization was evaluated for the comparison. The results show that (1) 18
      cases developed PEP, and they were significantly less in S group than in NS group
      (4 vs. 14 cases; P < 0.01); (2) Serum amylase was significantly lower in S group
      than in NS group (197.8 +/- 339.7 vs. 825.4 +/- 1253.4 U/l, respectively; P <
      0.05); (3) The intensity of abdominal pain was 3.4 +/- 0.8 in S group, compared
      to 4.1 +/- 1.2 in NS group; (4) Duration of pharmaceutical treatment was not
      significantly different between the two groups (4.2 +/- 1.4 vs. 6.1 +/- 2.3 days,
      in S and NS group, respectively); and (5) The total hospitalization cost was
      significantly less in S group (8928 +/- 2635 RMB) than in NS group (11288 +/-
      4325 RMB; P < 0.05). It is concluded that pancreatic duct stenting can reduce the
      incidence of PEP, shorten the duration of hospitalization, and therefore, lessen
      patients' financial burden. It is shown to be an effective way to prevent PEP.

PMID- 21739263
TI  - Comparison of macromolecular oxidation by reactive oxygen species in three
      bacterial genera exposed to different antibiotics.
AB  - Proteins and lipids maybe important targets of oxidation and this may alter their
      functions. We evaluated whether ceftazidima (CAZ), piperacillin (PIP),
      chloramphenicol (CMP), and ciprofloxacin (CIP) could oxidize the macromolecules
      in the three bacterial genera Staphylococcus aureus, Escherichia coli, and
      Pseudomonas aeruginosa. There was an increase in lipid peroxidation observed in
      these three species. However, this was lower in the Gram negative bacteria than
      in S. aureus. A reduction of the carbonyl residue in S. aureus with ciprofloxacin
      was observed whereas in Gram negative bacteria the antibiotics increased the
      carbonyl residue with respect to the control. Although the strains suffered a
      rise in advanced oxidation protein products (AOPP) in the presence of
      ciprofloxacin, the S. aureus strain had a smaller increase of AOPP than the other
      strains. The results described in this article provide data about the
      susceptibility of the three bacterial genera to the oxidative stress induced by
      the antibiotics studied.

PMID- 21739264
TI  - Clinical manifestation, imaging, and genotype analysis of two pedigrees with
      spinocerebellar ataxia.
AB  - The objective of this study was to analyze the clinical manifestation, imaging
      characteristics, genotype, and the relationship between the three aforementioned
      parameters in two pedigrees suffering from spinocerebellar ataxia. To evaluate
      the clinical manifestation of the two pedigrees and to compare the
      characteristics, we performed the MRI analysis of some patients from both
      pedigrees, while 2 ml of the peripheral blood sample was collected for gene
      analysis. The gene analysis data showed that pedigree 1 was certified
      spinocerebellar ataxia type-2 (SCA2); the CAG repeats in the proband, proband's
      mother, and proband's brother were 44, 36, and 38, respectively. The MRI revealed
      brainstem cerebellar atrophy and "cross sign" and "ordinate sign" of pons.
      Pedigree 2 was certified SCA1; the CAG repeats of the proband, proband's aunt,
      and proband's asymptomatic cousin were 60, 51, and 52, respectively. The MRI
      revealed cerebellar atrophy in these individuals. We, therefore, concluded that
      it was difficult to diagnose the SCA subset solely through the clinical
      manifestation. The imaging characteristics analysis and final diagnosis depended
      basically on gene analysis data.

PMID- 21739265
TI  - Improved curdlan fermentation process based on optimization of dissolved oxygen
      combined with pH control and metabolic characterization of Agrobacterium sp. ATCC
      31749.
AB  - A significant problem in scale-down cultures, rarely studied for metabolic
      characterization and curdlan-producing Agrobacterium sp. ATCC 31749, is the
      presence of dissolved oxygen (DO) gradients combined with pH control. Constant
      DO, between 5% and 75%, was maintained during batch fermentations by manipulating
      the agitation with PID system. Fermentation, metabolic and kinetic
      characterization studies were conducted in a scale-down system. The curdlan
      yield, intracellular nucleotide levels and glucose conversion efficiency into
      curdlan were significantly affected by DO concentrations. The optimum DO
      concentrations for curdlan production were 45-60%. The average curdlan yield,
      curdlan productivity and glucose conversion efficiency into curdlan were enhanced
      by 80%, 66% and 32%, respectively, compared to that at 15% DO. No apparent
      difference in the gel strength of the resulting curdlan was detected. The
      comparison of curdlan biosynthesis and cellular nucleotide levels showed that
      curdlan production had positive relationship with intracellular levels of UTP,
      ADP, AMP, NAD(+), NADH and UDP-glucose. The curdlan productivity under 45% DO and
      60% DO was different during 20-50 h. However, after 60 h curdlan productivity of
      both conditions was similar. On that basis, a simple and reproducible two-stage
      DO control process for curdlan production was developed. Curdlan production yield
      reached 42.8 g/l, an increase of 30% compared to that of the single agitation
      speed control process.

PMID- 21739266
TI  - Efficient synthesis of optically pure alcohols by asymmetric hydrogen-transfer
      biocatalysis: application of engineered enzymes in a 2-propanol-water medium.
AB  - We describe an efficient method for producing both enantiomers of chiral alcohols
      by asymmetric hydrogen-transfer bioreduction of ketones in a 2-propanol (IPA)
      water medium with E. coli biocatalysts expressing phenylacetaldehyde reductase
      (PAR: wild-type and mutant enzymes) from Rhodococcus sp. ST-10 and alcohol
      dehydrogenase from Leifsonia sp. S749 (LSADH). We also describe the detailed
      properties of mutant PARs, Sar268, and HAR1, which were engineered to have high
      activity and productivity in media composed of polar organic solvent and water,
      and the construction of three-dimensional structure of PAR by homology modeling.
      The K(m) and V(max) values for some substrates and the substrate specificity of
      mutant PARs were quite different from those of wild-type PAR. The results well
      explained the increased productivity of engineered PARs in IPA-water medium.

PMID- 21739267
TI  - The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6
      genetic polymorphism: effects of CYP enzyme inhibition by coadministration of
      paroxetine or fluvoxamine.
AB  - PURPOSE: To investigate the effects of coadministration of paroxetine or
      fluvoxamine on the pharmacokinetics of aripiprazole in healthy adult Japanese
      with different CYP2D6 genotypes. METHODS: Fourteen CYP2D6 extensive metabolizer
      (EM) and 14 CYP2D6 intermediate metabolizer (IM) subjects were coadministered a
      single oral dose of aripiprazole 3 mg after steady-state plasma concentrations of
      the SSRIs paroxetine (20 mg/day) or fluvoxamine (100 mg/day) were reached by
      repeated oral doses for 6-7 days. The pharmacokinetics of aripiprazole with and
      without coadministration of SSRIs were compared according to CYP2D6 genotypes.
      RESULTS: Coadministration of paroxetine, a potent CYP2D6 inhibitor, decreased
      systemic clearance (CL/F) of aripiprazole by 58 and 23% in CYP2D6 EMs and IMs,
      respectively, demonstrating that the percentage inhibition of CYP2D6 activity by
      coadministration of paroxetine was apparently greater in CYP2D6 EMs than in IMs.
      Coadministration of fluvoxamine, a less potent CYP3A4 inhibitor, decreased the
      CL/F of aripiprazole by 39% in CYP2D6 EMs and 40% in IMs, indicating the same
      inhibitory effect on CYP enzymes, regardless of the CYP2D6 genotype. Percent
      contribution of CYP2D6 to total CL/F (CYP2D6 plus CYP3A4) of aripiprazole
      estimated as a reduced percentage of CL/F by CYP enzyme inhibition was 62% for
      CYP2D6 EMs and 24% for IMs in paroxetine coadministration, and 40% for CYP2D6 EMs
      and 18% for IMs in fluvoxamine coadministration. CONCLUSIONS: There were marked
      differences in the degree of influence of paroxetine coadministration on the
      pharmacokinetics of aripiprazole between CYP2D6 EMs and IMs, but no apparent
      differences were found between two CYP2D6 genotypes in fluvoxamine
      coadministration. Aripiprazole can be used safely in combination with SSRIs that
      have a CYP enzyme-inhibitory action.

PMID- 21739268
TI  - Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their
      transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2.
AB  - We recently identified the transcription factor (TF) islet 1 gene product (ISL1)
      as a marker for well-differentiated pancreatic neuroendocrine tumors (P-NETs). In
      order to better understand the expression of the four TFs, ISL1, pancreatico
      duodenal homeobox 1 gene product (PDX1), neurogenin 3 gene product (NGN3), and
      CDX-2 homeobox gene product (CDX2), that mainly govern the development and
      differentiation of the pancreas and duodenum, we studied their expression in
      hormonally defined P-NETs and duodenal (D-) NETs. Thirty-six P-NETs and 14 D-NETs
      were immunostained with antibodies against the four pancreatic hormones, gastrin,
      serotonin, calcitonin, ISL1, PDX1, NGN3, and CDX2. The TF expression pattern of
      each case was correlated with the tumor's hormonal profile. Insulin-positive NETs
      expressed only ISL1 (10/10) and PDX1 (9/10). Glucagon-positive tumors expressed
      ISL1 (7/7) and were almost negative for the other TFs. Gastrin-positive NETs,
      whether of duodenal or pancreatic origin, frequently expressed PDX1 (17/18), ISL1
      (14/18), and NGN3 (14/18). CDX2 was mainly found in the gastrin-positive P-NETs
      (5/8) and rarely in the D-NETs (1/10). Somatostatin-positive NETs, whether
      duodenal or pancreatic in origin, expressed ISL1 (9/9), PDX1 (3/9), and NGN3
      (3/9). The remaining tumors showed labeling for ISL1 in addition to NGN3. There
      was no association between a particular TF pattern and NET features such as
      grade, size, location, presence of metastases, and functional activity. We
      conclude from our data that there is a correlation between TF expression patterns
      and certain hormonally defined P-NET and D-NET types, suggesting that most of the
      tumor types originate from embryologically determined precursor cells. The
      observed TF signatures do not allow us to distinguish P-NETs from D-NETs.

PMID- 21739269
TI  - E-cadherin and beta-catenin expression in sebaceous eyelid adenocarcinomas.
AB  - BACKGROUND: Since the E-cadherin-catenin complex is of importance in the
      cancerogenesis of epithelial tumors, we examined the expression of E-cadherin and
      beta-catenin in sebaceous adenocarcinomas of the eyelid and correlated the
      results with clinicopathological parameters. METHODS: The study included
      histological specimen of 32 patients with sebaceous adenocarcinomas of the
      eyelid. The expression of E-cadherin, beta-catenin, and Ki-67 nuclear antigen was
      analyzed by immunohistochemistry. RESULTS: The membranous expression of E
      cadherin and of beta-catenin was reduced in 17 (53%) patients and 18 (56%)
      patients, respectively, while elevated cytoplasmic levels and a nuclear
      accumulation of beta-catenin were found in 27 (84%) and six (19%) patients,
      respectively. The low expression of membranous beta-catenin was associated with a
      high degree of tumor infiltration (p = 0.02), high amount of inflammation (p =
      0.01), and high degree of poor tumor differentiation (p < 0.001). In a similar
      manner, a low membranous E-cadherin expression in tumors was significantly
      associated with poor tumor differentiation (p = 0.001) and high tumor cell
      proliferation rate (p = 0.004). The Ki-67 proliferation index was significantly
      higher in the group with low membranous E-cadherin expression than in the group
      with high membranous E-cadherin expression (62.3 +/- 20.8 versus 42.1 +/- 15.3; p
      = 0.004). The membranous E-cadherin expression and the membranous beta-catenin
      expression were significantly associated with each other (Fisher's exact
      probability test, p = 0.03). CONCLUSIONS: Sebaceous eyelid adenocarcinomas showed
      a decrease in the membranous expression of E-cadherin and of beta-catenin. These
      changes were associated with poor tumor differentiation and an increase in the
      tumor infiltration and inflammation, pointing at a potential role of a low E
      cadherin and low beta-catenin expression for poor prognosis of sebaceous eyelid
      adenocarcinomas. Correspondingly, the cell proliferation index and the expression
      of E-cadherin were inversely correlated with each other. The findings suggest
      that the immunohistochemical detection of a low E-cadherin and low beta-catenin
      expression may help in the examination and staging of sebaceous eyelid
      adenocarcinomas.

PMID- 21739270
TI  - [Peritoneal carcinomatosis after robotic-assisted radical cystectomy].
AB  - Among patients with metastatic urothelial cancer of the bladder, 16-25% develop
      peritoneal carcinomatosis. In the majority of cases peritoneal carcinomatosis is
      associated with multiple metastatic sites. Peritoneal metastases as the single
      site of metastatic deposits are rare and they have been described following
      laparoscopic radical nephroureterectomy or cystectomy. We report on a patient who
      developed peritoneal carcinomatosis as the single site of metastases 8 months
      after robotic-assisted radical cystectomy, extended pelvic lymphadenectomy and
      extracorporeal formation of an ileal neobladder for organ-confined, muscle
      invasive and poorly differentiated bladder cancer. The indication for robotic
      assisted radical cancer surgery for urothelial carcinoma of the upper or the
      lower urinary tract in patients with locally advanced or poorly differentiated
      cancer should be made with caution.

PMID- 21739271
TI  - Pair formation.
AB  - A multitype pair formation model for a one-sex population, without separation,
      with given type distribution of singles, produces a distribution of pairs with
      the given type distribution as a marginal distribution. The pair distribution can
      be seen as a nonnegative symmetric matrix. For this matrix representation
      formulas have been given years ago and have been widely used. The goal of the
      paper is to understand these formulas in probabilistic terms and give a meaning
      to their coefficients. Our approach connects the formulas to the problem of
      completing a substochastic matrix to a stochastic matrix. In this way the
      coefficients in the representation formula can be interpreted as preferences and
      insight can be gained into the set of distributions respecting given preferences.
      In order to put these questions into a wider perspective, the classical two-sex
      pair formation models are reviewed and embedded into the class of one-sex models,
      and dynamic models are designed that yield pair distributions as limit elements.

PMID- 21739272
TI  - [Giant cell arteritis with motor involvement of the upper trunk].

PMID- 21739273
TI  - [Muscular dystrophy due to mutations in anoctamin 5: clinical and molecular
      genetic findings].
AB  - Recessive mutations in the anoctamin 5 (ANO5) gene have been recently identified
      in families with limb girdle muscular dystrophy (LGMD2L) and distal non-dysferlin
      Miyoshi myopathy. Anoctamin 5 is supposed to be a putative calcium-activated
      chloride channel. We report five German patients (four index patients) with
      muscle dystrophy due to mutations in the ANO5 gene. Sequencing of the ANO5 exons
      5, 13 and 20 was performed to screen for a common c.191dupA mutation and two
      other reported mutations (c.1295C>G and p.R758C). The whole coding region of the
      ANO5 gene was sequenced to identify new mutations. Phenotypically, three patients
      showed LGMD and one patient Miyoshi type distal myopathy. One sibling had
      asymptomatic hyperCKemia. The age at onset was 64, 38 and 40 years in patients
      with LGMD and 23 years in the patient with distal myopathy. The four symptomatic
      patients showed remarkable asymmetric muscle involvement. There was marked CK
      elevation (11 to 30 times). Electron microscopy showed multifocal gaps in the
      sarcolemmal membrane. All patients harboured the common c.191dupA mutation in at
      least one allele. Two patients with LGMD were homozygous and the third patient
      and his asymptomatic sister were compound heterozygous for the c.191dupA mutation
      and a novel p.T548I mutation. The patient with distal myopathy harboured the
      p.R758C mutation in the second allele. Mutations in the ANO5 gene seem to be a
      relatively common cause of muscular dystrophy in Germany. Cases with late onset
      or asymptomatic hyperCKemia can occur. Clinically, asymmetric manifestation is
      typical.

PMID- 21739274
TI  - Valinomycin induced energy-dependent mitochondrial swelling, cytochrome c
      release, cytosolic NADH/cytochrome c oxidation and apoptosis.
AB  - In valinomycin induced stimulation of mitochondrial energy dependent reversible
      swelling, supported by succinate oxidation, cytochrome c (cyto-c) and sulfite
      oxidase (Sox) [both present in the mitochondrial intermembrane space (MIS)] are
      released outside. This effect can be observed at a valinomycin concentration as
      low as 1 nM. The rate of cytosolic NADH/cyto-c electron transport pathway is also
      greatly stimulated. The test on the permeability of mitochondrial outer membrane
      to exogenous cyto-c rules out the possibility that the increased rate of
      exogenous NADH oxidation could be ascribed either to extensively damaged or
      broken mitochondria. Accumulation of potassium inside the mitochondria, mediated
      by the highly specific ionophore valinomycin, promotes an increase in the volume
      of matrix (evidenced by swelling) and the interaction points between the two
      mitochondrial membranes are expected to increase. The data reported and those
      previously published are consistent with the view that "respiratory contact
      sites" are involved in the transfer of reducing equivalents from cytosol to
      inside the mitochondria both in the absence and the presence of valinomycin.
      Magnesium ions prevent at least in part the valinomycin effects. Rather than to
      the dissipation of membrane potential, the pro-apoptotic property of valinomycin
      can be ascribed to both the release of cyto-c from mitochondria to cytosol and
      the increased rate of cytosolic NADH coupled with an increased availability of
      energy in the form of glycolytic ATP, useful for the correct execution of
      apoptotic program.

PMID- 21739275
TI  - Translocation and oligomerization of Bax is regulated independently by activation
      of p38 MAPK and caspase-2 during MN9D dopaminergic neurodegeneration.
AB  - Bax is translocated into the mitochondrial membrane and oligomerized therein to
      initiate mitochondrial apoptotic signaling. Our previous study indicated that
      reactive oxygen species (ROS)-mediated activation of mitogen-activated protein
      kinase (MAPK) and caspase is critically involved in 6-hydroxydopamine (6-OHDA)
      mediated neurodegeneration. Here, we specifically attempted to examine whether
      and how these death signaling pathways may be linked to Bax translocation and
      oligomerization. We found that 6-OHDA treatment triggered translocation and
      oligomerization of Bax onto the mitochondria in MN9D dopaminergic neuronal cells.
      These events preceded cytochrome c release into the cytosol. Cross-linking assay
      revealed that co-treatment with a ROS scavenger or a pan-caspase inhibitor
      inhibited 6-OHDA-induced Bax oligomerization. Among several candidates of ROS
      activated MAPKs and caspases, we found that co-treatment with PD169316 or VDVAD
      specifically inhibited 6-OHDA-induced Bax oligomerization, suggesting critical
      involvement of p38 MAPK and caspase-2. Consequently, overexpression of a dominant
      negative form of p38 MAPK or a shRNA-mediated knockdown of caspase-2 indeed
      inhibited 6-OHDA-induced Bax oligomerization. However, activation of p38 MAPK and
      caspase-2 was independently linked to oligomerization of Bax. This specificity
      was largely confirmed with a Bax 6A7 antibody known to detect activated forms of
      Bax on the mitochondria. Taken together, our data suggest that there is an
      independent amplification loop of Bax translocation and oligomerization via
      caspase-2 and p38 MAPK during ROS-mediated dopaminergic neurodegeneration.

PMID- 21739276
TI  - Follicular atresia in the prepubertal spiny mouse (Acomys cahirinus) ovary.
AB  - This study was designed to determine follicular atresia in the newborn and the
      prepubertal spiny mouse. We analyzed the processes of follicle loss using
      classical markers of apoptosis (TUNEL reaction, active caspase-3) and autophagy
      (Lamp1). Numerous small clear vacuoles and autophagosomes as well as strong Lamp1
      staining were observed in dying oocytes of all follicle types, especially of the
      primordial and primary ones. Active caspase 3 and the TUNEL reaction were
      detected only in the granulosa cells of large secondary and antral follicles. The
      expression of apoptosis and autophagy markers was also changing during the
      prepubertal period. Western blot analysis indicated that at the moment of birth,
      females undergo an increased rate of follicular atresia mediated by autophagy,
      while apoptosis is the dominant form of ovarian atresia in consecutive postnatal
      days. On the basis of these observations, we concluded that apoptosis and
      autophagy are involved in follicular atresia and these processes are cell and
      developmental stage-specific.

PMID- 21739277
TI  - The non-steroidal anti-inflammatory drugs Sulindac sulfide and Diclofenac induce
      apoptosis and differentiation in human acute myeloid leukemia cells through an AP
      1 dependent pathway.
AB  - Acute myeloid leukemia is a heterogeneous disease with varying genetic and
      molecular pathologies. Non-steroidal anti-inflammatory drugs (NSAIDs) have been
      proven to possess significant anti-proliferative potential in various cancer
      cells in vitro and in vivo. Hence, treatment with these agents can be utilized to
      study disease specific anti-proliferative pathways. In this study, a total number
      of 42 bone marrow derived CD34(+) selected de novo AML patient samples and the
      AML cell lines THP-1 and HL-60 were treated with the NSAIDs Sulindac sulfide and
      Diclofenac. We analyzed viability, apoptosis, differentiation and addressed the
      molecular mechanisms involved. We found a consistent induction of apoptosis and
      to some extent an increased myeloid differentiation capacity in NSAID treated AML
      cells. Comprehensive protein and gene expression profiling of Diclofenac treated
      AML cells revealed transcriptional activation of GADD45alpha and its downstream
      MAPK/JNK pathway as well as increased protein levels of the caspase-3 precursor.
      This pointed towards a role of the c-Jun NH(2)-terminal kinase (JNK) in NSAID
      mediated apoptosis that we found indeed to be dependent on JNK activity as
      addition of a specific JNK-inhibitor abrogated apoptosis. Furthermore, the AP-1
      transcription factor family members' c-Jun, JunB and Fra-2 were transcriptionally
      activated in NSAID treated AML cells and re-expression of these transcription
      factors led to activation of GADD45alpha with induction of apoptosis.
      Mechanistically, we demonstrate that NSAIDs induce apoptosis in AML through a
      novel pathway involving increased expression of AP-1 heterodimers, which by
      itself is sufficient to induce GADD45alpha expression with consecutive activation
      of JNK and induction of apoptosis.

PMID- 21739278
TI  - Optimization of digestion parameters for analysing the total sulphur of mine
      tailings by inductively coupled plasma optical emission spectrometry.
AB  - The oxidation of sulphidic mine tailings and consequent acid generation poses
      challenges for the environment. Accurate and precise analysis of sulphur content
      is necessary for impact assessment and management of mine tailings. Here, the
      authors aim at developing a rapid and easy digestion procedure, which may analyse
      and measure the total amount of sulphur in mine tailings by using inductively
      coupled plasma. For evaluating effects of several variables, the researchers used
      a univariate (analysis of variance (ANOVA)) strategy and considered factors such
      as composition of the acid mixture, heating time, and refluxing device to
      optimize the performance. To do the experiment, the researchers have used two
      certified reference materials (KZK-1 and RTS-2) and samples of tailings from
      Musselwhite mine. ANOVA result shows that heating time is the most influencing
      factor on acid digestion of the reference materials whereas in case of a
      digestion of tailings sample, hydrochloric acid proved to be the most significant
      parameter. Satisfactory results between the measured and referenced values are
      found for all experiments. It is found that the aqua regia (1 ml HNO(3) + 3 ml
      HCl) digestion of 0.1 g of samples after only 40 min of heating at 95 degrees C
      produced fast, safe, and accurate analytical results with a recovery of 97% for
      the selected reference materials.

PMID- 21739279
TI  - Organophosphate pesticide environmental exposure: analysis of salivary
      cholinesterase and carboxilesterase activities in preschool children and their
      mothers.
AB  - A pilot study was conducted to evaluate the usefulness of salivary cholinesterase
      and carboxylesterase as biomarkers of exposure to environmental organophosphate
      pesticides. Ninety samples were obtained from women and 62 samples from their
      preschool-aged children who live near an agricultural area of the Upper Valley of
      the Negro River (Patagonia, Argentina) where pesticides are applied 6 months a
      year. Each participant donated two samples under similar conditions: one in the
      pre-exposure period and another during the pulverization period. Demographic
      information, potential confounders, and risk behaviors were registered. Active or
      passive smoking had no effect on these enzyme activities in either group. During
      the pulverization period, cholinesterase activity was not detectable in 76% of
      the children's samples and 23% of the mothers' samples. Comparing samples
      collected during the pulverization period with respect to the pre-pulverization
      period, the average mother and child cholinesterase activity decreased by 65.7%
      (p < 0.001) and 85.8% (p < 0.001), respectively. Also, mother and child
      carboxylesterase activity decreased by 27.5% (p < 0.001) and 41.9% (p < 0.01),
      respectively. Child carboxylesterase activity in the pulverization period was
      associated to the habit of eating dust outdoors (p < 0.01). The most frequent
      inhibition levels observed for cholinesterase and carboxylesterase activity were
      between 70-100% and 0-29%, respectively, in both groups studied. This shows that
      at the same level of exposure, cholinesterase was more sensitive to inhibition
      than carboxylesterase. Therefore, carboxylesterase might more properly reflect
      the degree of environmental organophosphate exposure and may have potential as a
      novel tool for biomonitoring.

PMID- 21739280
TI  - Comparing volunteer and professionally collected monitoring data from the rocky
      subtidal reefs of Southern California, USA.
AB  - Volunteer-based citizen monitoring has increasingly become part of the natural
      resources monitoring framework, but it is often unclear whether the data quality
      from these programs is sufficient for integration with traditional efforts
      conducted by professional scientists. At present, the biological and physical
      characteristics of California's rocky reef kelp forests are concurrently
      monitored by two such groups, using similar methodologies--underwater visual
      census (UVC) of fish, benthic invertebrates, and reef habitat, though the
      volunteer group limits their sampling to transects close to the reef surface and
      they use a more constrained list of species for enumeration and measurement.
      Here, we compared the data collected from 13 reefs that were sampled by both
      programs in 2008. These groups described relatively similar fish communities,
      total fish abundance and abundance of the dominant fish species but there were
      some differences in the measured size distributions of the dominant fish species.
      Descriptions of the benthic invertebrate community were also similar, though
      there were some differences in relative abundance that may have resulted from the
      less detailed subsampling protocols used by the volunteers. The biggest
      difference was in characterization of the physical habitat of the reefs, which
      appeared to result from selection bias of transect path by the volunteer program
      towards more complex structured sections of a reef. Changes to address these
      differences are relatively simple to implement and if so, offer the promise of
      better integration of the trained volunteer monitoring with that of professional
      monitoring groups.

PMID- 21739281
TI  - A strategic management model for evaluation of health, safety and environmental
      performance.
AB  - Strategic health, safety, and environmental management system (HSE-MS) involves
      systematic and cooperative planning in each phase of the lifecycle of a project
      to ensure that interaction among the industry group, client, contractor,
      stakeholder, and host community exists with the highest level of health, safety,
      and environmental standard performances. Therefore, it seems necessary to assess
      the HSE-MS performance of contractor(s) by a comparative strategic management
      model with the aim of continuous improvement. The present Strategic Management
      Model (SMM) has been illustrated by a case study and the results show that the
      model is a suitable management tool for decision making in a contract
      environment, especially in oil and gas fields and based on accepted international
      standards within the framework of management deming cycle. To develop this model,
      a data bank has been created, which includes the statistical data calculated by
      converting the HSE performance qualitative data into quantitative values. Based
      on this fact, the structure of the model has been formed by defining HSE
      performance indicators according to the HSE-MS model. Therefore, 178 indicators
      have been selected which have been grouped into four attributes. Model output
      provides quantitative measures of HSE-MS performance as a percentage of an ideal
      level with maximum possible score for each attribute. Defining the strengths and
      weaknesses of the contractor(s) is another capability of this model. On the other
      hand, this model provides a ranking that could be used as the basis for decision
      making at the contractors' pre-qualification phase or during the execution of the
      project.

PMID- 21739282
TI  - Organochlorine pesticides and polychlorinated biphenyls in common buzzard (Buteo
      buteo) from Sicily (Italy).
AB  - In the present study, we investigated the concentrations and distribution of
      organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs) in
      intestine, liver, and muscle samples of 11 common buzzards (Buteo buteo) from
      Sicily used as bioindicator for monitoring pollution in environment. All samples
      of common buzzards were collected at the "Recovery Center of Wild Fauna" of
      Palermo, through the Zooprophilactic Institute. Quantitative determination of OCs
      and PCBs in the samples examined has been carried out using HRGC-ECD and GC-MS.
      The results obtained show the presence of concentrations of ?DDT and ?PCB in
      almost all samples. Regarding ?DDT (4,4(')-DDE, 2,4(')-DDD, 4,4(')-DDD, 2,4(')
      DDT, and 4,4(')-DDT), the highest concentrations were found in intestine (0.411
      +/- 0.050 MUg/g) followed by muscle (0.130 +/- 0.017 MUg/g) and liver samples
      (0.109 +/- 0.014 MUg/g). As regards the ?PCB congeners (PCB-28, PCB-52, PCB-95,
      PCB-99, PCB-101, PCB-110, PCB-138, PCB-146, PCB-149, PCB-151, PCB-153, PCB-170,
      PCB-177, PCB-180, PCB-183, and PCB-187), the highest concentrations were found in
      intestine (1.686 +/- 0.144 MUg/g) followed by liver (1.064 +/- 0.162 MUg/g) and
      muscle samples (0.797 +/- 0.078 MUg/g). Our data deserve particular attention not
      only for their significance but especially because they were recorded in Sicily,
      a region with a very low risk of environmental pollution due to the shortage of
      industries.

PMID- 21739283
TI  - Changing environment and urban identity following open-cast mining and thermic
      power plant in Turkey: case of Soma.
AB  - This paper is a summary of a project changed into a book named by "Changing
      Environment, City and Identity in Soma with the Geographical Evaluations" issued
      on May 2005. In this research, Soma, which is one of the most remarkable
      districts in Manisa in the West Anatolia from the point of economical figures, is
      assessed with its physical environment potential, improving economical activities
      and changing socio-economical structure. Owing to the open coal basins in the
      northeast and southwest of the district where lignite is produced and the impact
      of the thermic power plant near the city centre, Soma has changed on a large
      scale. This change has introduced some environmental problems into the district
      such as the devastation of the forestry land; the infertility of farming land;
      and soil, water and air pollution. Even though the change under discussion has
      led to many problems to deal with, it has also influenced its socio-economical
      structure to a large extent and revealed new type of inhabitants having different
      life expectations and aims. In conclusion, in this article, changing environment
      and city structure after lignite processing and thermic station establishment in
      Soma are discussed through the effective geographical factors. The new city
      profile formed by the local dynamics in question is evaluated according to the
      data obtained by the studies made in the neighbourhood.

PMID- 21739284
TI  - [100 years after Kienbock's description: review of the etiology of Kienbock's
      disease from a historical perspective].
AB  - Kienbock's disease (KD) leads to collapse of the lunate bone with severe
      consequences for the wrist function which for some patients may result in
      occupational invalidity. The many synonyms of KD (aseptic necrosis or avascular
      necrosis) insinuate that the true etiopathology remains poorly understood. This
      reviews aims at exploring the level of evidence which brought forward the
      different hypotheses on the origin of KD. The widespread theories about the
      origin were formed about 100 years ago but a specific therapy is still not within
      reach. Although the cause of the disease remains essentially unknown it is
      officially recognized as an occupational disease in Germany. Empirical attempts
      to explain the etiopathology are based on compression of the lunate, impaired
      vascularity through vibration exposition, fracture and dislocation of the lunate
      from the radiolunate fossa. The level of evidence urges a cautious interpretation
      of currently discussed hypotheses on the etiology of KD.

PMID- 21739285
TI  - Electronic medical records and same day patient tracing improves clinic
      efficiency and adherence to appointments in a community based HIV/AIDS care
      program, in Uganda.
AB  - Patients who miss clinic appointments make unscheduled visits which compromise
      the ability to plan for and deliver quality care. We implemented Electronic
      Medical Records (EMR) and same day patient tracing to minimize missed
      appointments in a community-based HIV clinic in Kampala. Missed, early, on
      schedule appointments and waiting times were evaluated before (pre-EMR) and 6
      months after implementation of EMR and patient tracing (post-EMR). Reasons for
      missed appointments were documented pre and post-EMR. The mean daily number of
      missed appointments significantly reduced from 21 pre-EMR to 8 post-EMR. The main
      reason for missed appointments was forgetting (37%) but reduced significantly by
      30% post-EMR. Loss to follow-up (LTFU) also significantly decreased from 10.9 to
      4.8% The total median waiting time to see providers significantly decreased from
      291 to 94 min. Our findings suggest that EMR and same day patient tracing can
      significantly reduce missed appointments, and LTFU and improve clinic efficiency.

PMID- 21739286
TI  - Impact of a mHealth intervention for peer health workers on AIDS care in rural
      Uganda: a mixed methods evaluation of a cluster-randomized trial.
AB  - Mobile phone access in low and middle-income countries is rapidly expanding and
      offers an opportunity to leverage limited human resources for health. We
      conducted a mixed methods evaluation of a cluster-randomized trial exploratory
      substudy on the impact of a mHealth (mobile phone) support intervention used by
      community-based peer health workers (PHW) on AIDS care in rural Uganda. 29 PHWs
      at 10 clinics were randomized by clinic to receive the intervention or not. PHWs
      used phones to call and text higher level providers with patient-specific
      clinical information. 970 patients cared for by the PHWs were followed over a 26
      month period. No significant differences were found in patients' risk of
      virologic failure. Qualitative analyses found improvements in patient care and
      logistics and broad support for the mHealth intervention among patients, clinic
      staff, and PHWs. Key challenges identified included variable patient phone
      access, privacy concerns, and phone maintenance.

PMID- 21739287
TI  - HIV attitudes, awareness and testing among older adults in Africa.
AB  - In Africa, older adults aged 50 and older are still sexually active and play a
      critical role as caregivers, yet little is known about their attitudes towards
      HIV and awareness of services. In this study, surveys were conducted in nine
      African sites. A multilevel model was fitted to evaluate the relationship between
      age and outcome variables. The study reveals that people aged 50 years and older
      have lower levels of HIV-related knowledge and awareness than those aged 25-49.
      Older adults were less likely to have been tested for HIV and women aged 50 and
      older showed particularly low levels of awareness.

PMID- 21739288
TI  - Changes in the prevalence of injection drug use among adolescents and young
      adults in large U.S. metropolitan areas.
AB  - Young injection drug users (IDUs) are at risk for acquiring blood-borne diseases
      like HIV and Hepatitis C. Little is known about the population prevalence of
      young IDUs. We (1) estimate annual population prevalence rates of young IDUs
      (aged 15-29) per 10,000 in 95 large U.S. metropolitan statistical areas (MSAs)
      from 1992 to 2002; (2) assess the validity of these estimates; and (3) explore
      whether injection drug use among youth in these MSAs began to rise after HAART
      was discovered. A linear mixed model (LMM) estimated the annual population
      prevalence of young IDUs in each MSA and described trends therein. The population
      prevalence of IDUs among youths across 95 MSAs increased from 1996 (mean = 95.64)
      to 2002 (mean = 115.59). Additional analyses of the proportion of young IDUs
      using health services suggest this increase may have continued after 2002. Harm
      reduction and prevention research and programs for young IDUs are needed.

PMID- 21739289
TI  - Mother's CD4+ count moderates the risk associated with higher parity for late
      postnatal HIV-free survival of breastfed children: an individual patient data
      meta-analysis of randomized controlled trials.
AB  - Risk association studies of late postnatal outcomes for children breastfed by HIV
      1 positive mothers have had inconsistent findings and have not explored
      interactions among risk factors. This study addresses these limitations through
      an individual patient data (IPD) meta-analysis of HIV-free survival outcomes of
      nine randomized controlled trials to prevent early mother-to-child transmission
      of HIV-1. The pooled sample consisted of 3,324 African children in resource
      limited settings who survived to age 28 days and were at-risk of acquiring HIV
      through breast milk. Based on a proportional hazards mixed effects meta-analysis,
      the composite endpoint of HIV-1 infection and all-cause mortality was found to be
      significantly associated with maternal immune status (CD4(+) >=350 cells/mm(3),
      HR 0.59 95% CI (0.39, 0.87)), infant preterm delivery (gestational age <37 weeks,
      1.40 (1.03, 1.89)), infant oral candidiasis infection (1.87, (1.53, 2.29)), and
      occurrence of breast abnormality before breastfeeding cessation (2.56 (1.90,
      3.46)). A significant interaction between mother's parity (any previous
      pregnancy) and CD4(+) count >=350 (HR 0.63 (0.40, 0.99), P-value = 0.045)
      suggested that higher CD4(+) count offsets the risk associated with higher
      parity. Further research is needed to elucidate the moderating effect of immune
      status on the risk associated with high parity and adverse late postnatal
      outcomes for infants breastfed by HIV-infected mothers in the absence of
      antiretroviral treatment.

PMID- 21739290
TI  - Reducing sexual HIV/STI risk and harmful alcohol use among female sex workers in
      Mongolia: a randomized clinical trial.
AB  - This study examined the efficacy of an enhanced intervention to reduce sexual
      risk of HIV/STI and harmful alcohol use among female sex workers in Mongolia.
      Women (n = 166) were recruited and randomized to either (1) a relationship-based
      HIV sexual risk reduction intervention; (2) the same sexual risk reduction
      intervention plus motivational interviewing; or (3) a control condition focused
      on wellness promotion. At three and six month follow-up, both treatment
      interventions and the wellness promotion condition were effective in reducing the
      percentage and the number of unprotected acts of vaginal sex with paying partners
      in the past 90 days. All three conditions demonstrated efficacy in reducing
      harmful alcohol use. No significant differences in effects were observed between
      conditions. Findings suggest that even low impact behavioral interventions can
      achieve considerable reductions of HIV/STI risk and harmful alcohol use with a
      highly vulnerable population in a low resourced setting.

PMID- 21739291
TI  - Patient-level moderators of the efficacy of peer support and pager reminder
      interventions to promote antiretroviral adherence.
AB  - Antiretroviral therapy (ART) greatly reduces morbidity and mortality for people
      with HIV/AIDS. However, for optimal effectiveness patients must achieve strict
      adherence to dosing regimens, which is difficult to maintain over the long term.
      Interventions to improve adherence have shown promising results, but with small
      effects. One explanation for small overall effects is that some patient subgroups
      are less able to benefit from current interventions; however, this explanation
      lacks empirical support. This study used multilevel modeling of data from a
      randomized controlled trial in an exploratory analysis to assess whether patient
      factors moderated the impact of peer support and pager reminders on ART adherence
      and biological markers of HIV. According to 272 interaction models using an alpha
      corrected significance criteria, none of 34 patient characteristics significantly
      moderated either intervention. Findings suggest that intervention research might
      more profitably focus on other ways of improving effects, like individual patient
      needs, rather than target subgroups.

PMID- 21739292
TI  - Current advances in prenatal imaging of congenital diaphragmatic [corrected]
      hernia.
AB  - Congenital diaphragmatic hernia, despite advances in therapy, remains a complex
      condition with significant morbidity and mortality. The etiology of the disorder
      is still incompletely understood, though the pulmonary hypoplasia and pulmonary
      hypertension that develop secondarily must be overcome to improve survival.
      Prenatal US and fetal MRI have helped in the development of a greater
      understanding of this disease. Also with these modalities, measurement techniques
      have been developed in an attempt to provide prognosticators for the development
      of pulmonary hypoplasia and pulmonary hypertension. There is a broad range of
      approaches for performing these measurements, and variability among imaging
      centers is noted. Despite inconsistent approaches, these techniques have become
      the foundation for counseling and prenatal and postnatal therapy. It is hoped
      that with further research with prenatal US and fetal MRI and the development of
      innovative medical and surgical therapies that the morbidity and mortality of
      children with congenital diaphragmatic hernias can be significantly reduced.

PMID- 21739293
TI  - Reward and uncertainty favor risky decision-making in pilots: evidence from
      cardiovascular and oculometric measurements.
AB  - In this paper we examined plan continuation error (PCE), a well known error made
      by pilots consisting in continuing the flight plan despite adverse meteorological
      conditions. Our hypothesis is that a large range of strong negative emotional
      consequences, including those induced by economic pressure, are associated with
      the decision to revise the flight plan and favor PCE. We investigated the
      economic hypothesis with a simplified landing task (reproduction of a real
      aircraft instrument) in which uncertainty and reward were manipulated. Heart rate
      (HR), heart rate variability (HRV) and eye tracking measurements were performed
      to get objective clues both on the cognitive and emotional state of the
      volunteers. Results showed that volunteers made more risky decisions under the
      influence of the financial incentive, in particular when uncertainty was high.
      Psychophysiological examination showed that HR increased and total HRV decreased
      in response to the cognitive load generated by the task. In addition, HR also
      increased in response to the financially motivated condition. Eventually,
      fixation times increased when uncertainty was high, confirming the difficulty in
      obtaining/interpreting information from the instrument in this condition. These
      results support the assumption that risky-decision making observed in pilots can
      be, at least partially, explained by a shift from cold to hot (emotional)
      decision-making in response to economic constraints and uncertainty.

PMID- 21739294
TI  - Heart rate variability as a marker of self-regulation.
AB  - Self-regulation is central to many of the most important individual and societal
      problems today. We sought to determine whether the relationship between self
      regulation and heart rate variability (HRV) could be replicated and extended. We
      hypothesized that baseline HRV would predict persistence on an anagram task, and
      that under conditions requiring greater self-control, HRV would increase. Two
      groups were given the same set of difficult and unsolvable anagrams. To induce
      self-regulatory fatigue, the suppression group was asked to try to not think of a
      white bear while the expression group was asked to try to think of a white bear.
      Baseline HRV predicted persistence on the unsolvable anagram. Both groups
      demonstrated changes in HRV relative to baseline, although we were unable to
      replicate findings that HRV was elevated during high self-regulatory effort. We
      were, however, able to replicate findings that the expression group persisted
      longer on the anagram task compared to the suppression group but only when
      accounting for physical activity scores. The present study advances our knowledge
      of the relationship between HRV and self-regulation, so that we can more
      successfully treat those with seriously impaired self-control.

PMID- 21739295
TI  - Safety practices in relation to home ownership among urban Mexican immigrant
      families.
AB  - We examined home safety hazards, comparing renter- to owner-occupied housing
      among urban, immigrant Mexican families. METHODS: Interviews and home inspections
      were conducted among urban, Spanish-speaking immigrant families with children. We
      estimated weighted hazard prevalence and used logistic regression to compare
      owner- and renter-occupied homes. Of 313 eligible households, 250 (80%) enrolled.
      Respondents were predominantly Mexican-born (99%), low income (72.6%) and lower
      education (92.3%). Most homes had fire, burn, fall, poisoning, electrocution and
      fire escape hazards, including high tap water temperatures (76.4%; 95% CI: 69.0,
      83.7%), no working smoke alarms (60.0%; 51.3, 68.8%), slippery bathtub/shower
      surfaces (58.7%; 49.9, 67.5%), blocked fire escape routes (55.9%; 47.2, 64.5%)
      and child-accessible medications (71.0%; 60.1, 81.3%). After adjustment for
      sociodemographics, fire escape (OR = 8.8; 95% CI: 2.8, 27.7), carbon monoxide
      poisoning (OR = 2.9; 1.4, 6.2) and drowning (OR = 3.5; 1.3, 9.4) hazards were
      more likely in owner- than renter-occupied homes. Housing age and type explained
      most differences. Many urban, immigrant Spanish-speaking families live in unsafe
      homes. For this population, housing safety programs should be targeted based on
      housing age and type rather than tenure.

PMID- 21739296
TI  - Communication with the uncommunicable: proceedings of the Ethics Committee.

PMID- 21739297
TI  - A 26-year-old woman with recurrent loss of consciousness.
AB  - The case of a 26-year-old woman with congenital long QT syndrome and recurrent
      arrhythmic syncope which had been misdiagnosed as a seizure disorder is
      presented. Useful criteria for discriminating between loss of consciousness due
      to congenital long QT syndrome and loss of consciousness caused by seizure
      activity are discussed. The multiple potential causes and clinical implications
      of a prolonged QT interval, as well as the clinical features and management of
      congenital long QT syndrome are reviewed.

PMID- 21739298
TI  - Children with generalized anxiety disorder do not have peer problems, just fewer
      friends.
AB  - A common assumption is that all youth with anxiety disorders (AD) experience
      impaired peer relationships relative to healthy control children. Social
      impairments have been identified among youth with certain AD (e.g., social
      anxiety disorder; SAD), but less is known about the peer relationships of
      children with generalized anxiety disorder (GAD). We therefore compared the
      interpersonal functioning of youth with GAD, SAD, and controls (6-13 years).
      Despite having relatively fewer friends overall, children with GAD did not differ
      from controls in terms of the likelihood of having a best friend, participation
      in groups/clubs, and parent ratings of social competence. In comparison, youth
      with SAD were less socially competent, had fewer friends and difficulty making
      new friends compared to controls. Findings suggest that peer difficulties are not
      a universal feature of all childhood AD and highlight a need to better understand
      the social experiences and functioning of children with GAD.

PMID- 21739299
TI  - Antipsychotic-induced somnolence in mothers with schizophrenia.
AB  - Although it is known that many antipsychotic drugs, at the doses prescribed for
      schizophrenia, are sedative and cause daytime drowsiness, the effect of
      potentially diminished vigilance on parenting parameters has not been studied.
      The aim of this paper is to advise clinicians about sedative load in mothers who
      are prescribed antipsychotic medication. A Medline search was conducted into the
      sedative effects of antipsychotics, with the following search terms: sleep;
      sedation; somnolence; wakefulness; antipsychotics; schizophrenia, parenting,
      maternal behavior, and custody. The results showed that antipsychotic drugs
      differ in their propensity to induce sedation and do so via their effects on a
      variety of neurotransmitter systems. It is important to note that mothers with
      schizophrenia risk losing custody of their infants if they are perceived as
      potentially neglectful because of excessive daytime sleepiness. Clinicians must
      choose antipsychotic medications carefully and monitor for sedative effects
      whenever the patient has important responsibilities that require the maintenance
      of vigilance.

PMID- 21739300
TI  - [Special aspects of the emergency medical care of head and neck injuries].
AB  - The overall incidence of severe head, face and neck injuries as seen from the
      German Trauma Registry of the National Association of German Trauma Surgeons is
      81.3%. The leading causes of death among these patients are hemorrhage and severe
      traumatic brain injury. The aim of prehospital emergency medical care is to
      stabilize vital functions in order to ensure primary survival and to reduce
      morbidity with appropriate prehospital treatment of the individual injuries
      within the overall injury pattern. In this review, special aspects as well as
      pitfalls of the prehospital management of patients with head, face and neck
      injuries are demonstrated. Prehospital airway management concepts as well as
      concepts for stopping bleeding in the head, face and neck region are discussed in
      detail.

PMID- 21739301
TI  - [Hemangiopericytoma of the buccal mucosa. A case report].
AB  - Hemangiopericytoma describes a rare mesenchymal neoplasm which can occur at any
      site on the body and represents 1% of vascular tumors. Histologically, it is
      characterized by a vascular pattern with high cellularity. These tumors occur in
      particular near the torso and surface variants are rare. Due to the unspecific
      clinical picture, it is often confused with other  benign mesenchymal tumors. The
      heterogenous course and high risk of recurrence with hemangiopericytomas
      necessitate long-term clinical follow-up.

PMID- 21739302
TI  - Heart rate variability and exercise capacity of patients with repaired tetralogy
      of Fallot.
AB  - Heart rate variability (HRV) has been used as a reliable method to detect cardiac
      autonomic nervous system activity. Peak oxygen uptake (VO(2) peak) has been a
      predictor of death for adults with repaired tetralogy of Fallot (TOF). This study
      investigated the correlation between HRV and exercise capacity in 30 patients
      with TOF after surgery for total correction. The median age of the patients was
      14 years (range, 9-25 years), and the median follow-up period was 11.6 months
      (range, 5.3-20.2 months). Low- and high-frequency-domain HRV significantly
      correlated with VO(2) peak (r = 0.56, P = 0.001 and r = 0.44, P = 0.02,
      respectively). After the 1-year follow-up evaluation, VO(2) peak and HRV analysis
      did not differ from those at entry to the study. However, low- and high-frequency
      domain HRV still correlated significantly with VO(2) peak (r = 0.43, P = 0.03 and
      r = 0.52, P = 0.007, respectively). Left ventricular early diastolic myocardial
      velocity was most closely correlated with the VO(2) peak (r = 0.51, P = 0.005).
      Impaired cardiovascular autonomic control and left ventricular diastolic
      dysfunction may be responsible for exercise intolerance in patients with repaired
      TOF. Long-term follow-up evaluation with exercise testing and 24-h Holter
      monitoring are warranted.

PMID- 21739303
TI  - Superior mesenteric artery first combined with uncinate process approach versus
      uncinate process first approach in pancreatoduodenectomy: a comparative study
      evaluating perioperative outcomes.
AB  - PURPOSE: During pancreatoduodenectomy (PD), two techniques have been described to
      dissect the head of pancreas, viz. the superior mesenteric artery (SMA) approach
      by dissecting the uncinate process and the uncinate process first approach.
      METHODS: Forty-four consecutive patients, who underwent PD between June 2009 and
      April 2010, were analyzed. Thirty patients underwent the SMA first approach along
      with uncinate dissection (group 1), while 14 patients underwent the uncinate
      process first approach (group 2). RESULTS: There were 30 male and 14 female
      patients. The median age was 51 years (range 19-76 years). Median intraoperative
      blood loss in group 1 was 800 ml, while that in group 2 was 600 ml. A mean of
      0.52 units of blood were transfused in group 1 (range 0-3) compared to 0.2 units
      in group 2 (range 0-1). The median operative time in group 1 was 457.5 min and
      the median operative time was 450 min in group 2. Complication rate was 40% and
      14.3% in groups 1 and 2, respectively. Median duration of hospital stay was 14
      days in group 1 and 12.5 days in group 2. Median nodes resected in group 1 were 8
      (range 0-26), while in group 2 they were 9 (range 2-14). Resection margins were
      positive in two cases (one in each group). There were two mortalities in group 1
      and no mortalities in group 2. None of the above differences were significant.
      CONCLUSIONS: SMA first is a safe technique. It compares well with the uncinate
      first approach in terms of operative time, blood loss, number of lymph nodes
      retrieved, margin positivity and operative morbidity. Both techniques may be
      useful in situations such as a large uncinate process tumor or when superior
      mesenteric vein/portal vein/superior mesenteric artery involvement is suspected
      or present. Further studies, evaluating data related to specific predefined
      uncinate tumors, would be the next logical step in further defining the precise
      role of these techniques.

PMID- 21739304
TI  - Surgery for liver metastases originating from sarcoma-case series.
AB  - INTRODUCTION: Liver metastases originating from various types of sarcoma are a
      rare reason for hepatic resection. So far, even multicentre studies do hardly
      provide statistically relevant sample sizes. Thus, review of available data can
      provide surgeons with useful information in similar cases. Therefore, this study
      can be regarded more as a contribution to this pool of data than as a stand-alone
      paper. PATIENTS AND METHODS: The study includes 10 women and five men who
      underwent subtotal hepatic resection for solitary (n = 4) and multiple (n = 11)
      liver metastases originating from sarcoma. The median tumour diameter was 60 mm
      (range 20-200 mm). RESULTS: Morbidity was 33%. One patient died within 30 days
      after surgery. Resection was complete (R0) in 67%. Median overall survival was
      33.6 months, 5-year survival 27%. The use of Pringle manoeuvre was significantly
      associated with poorer outcome (p = 0.014) and shorter period of recurrence-free
      survival (p = 0.012). Diameter of liver lesion over 50 mm showed significantly
      shorter recurrence-free survival (p = 0.042). CONCLUSION: Hepatic resection may
      be beneficial in patients with isolated sarcoma metastasis in the liver.

PMID- 21739305
TI  - Iodine content in salt.

PMID- 21739306
TI  - Improved outcome of Henoch-Schonlein purpura nephritis by early intensive
      treatment.
AB  - OBJECTIVE: To evaluate the different therapies used to treat mild, moderate and
      severe Henoch-Schonlein purpura nephritis (HSPN) patients and to identify the
      most effective treatment. METHODS: One hundred and eighty six children were
      evaluated retrospectively. They were divided into mild, moderate and severe
      condition groups. Different therapeutic protocols of non-steroid therapy,
      hydrocortisone sodium succinate (HCSS) therapy, methylprednisolone (MP) pulse
      therapy, and MP in combination with tripterygium glycoside (TG) therapy were used
      to treat the different groups. RESULTS: After 4 wk, in the mild group, patients
      were more likely to respond to HCSS therapy than non-steroid therapy (P < 0.05).
      Moderate HSPN patients were more likely to respond to MP therapy than HCSS
      therapy (P < 0.05). Severe HSPN patients were more likely to respond to MP in
      combination with TG than single MP therapy (P < 0.05). At last follow-up, all
      children had normal urinalysis, blood pressure and serum urea and creatinine. In
      the mild group, the mean duration of proteinuria was shorter in HCSS therapy
      group than in non-steroid therapy group (P < 0.05). In the moderate group, the
      mean duration of proteinuria was shorter in MP pulse therapy group than in HCSS
      therapy group (P < 0.05). CONCLUSIONS: The present study has demonstrated a
      superior effect of HCSS therapy in patients with mild HSPN disease, of MP therapy
      in patients with moderate disease, and of MP in combination with TG therapy in
      patients with severe disease. Intensive therapy administered initially reduces
      the duration of urinary protein abnormality.

PMID- 21739307
TI  - ZCCHC12, a potential molecular marker of papillary thyroid carcinoma: a
      preliminary study.
AB  - A gene expression profile analysis using an Affymetrix HG-U133 Plus 2.0
      microarray with probes for 38,500 human full-length cDNAs was performed on a
      primary papillary thyroid carcinoma (PTC) and a nodular goiter (NG). ZCCHC12 was
      the gene with the most significant differential expression between PTC and NG,
      and this was verified using fluorescent quantitative PCR (FQ-PCR). A total of
      9,485 genes were detected with a difference in transcription levels between PTC
      and NG. Of these, 2,098 were up-regulated with a signal log ratio (SLR) >= 1 and
      1,714 were down-regulated with an SLR <= -1. Among these up-regulated and down
      regulated genes, 12 genes were significantly up-regulated (SLR >= 5.0) and 6
      genes were significantly down-regulated (SLR <= -5.0). The SLR of the ZCCHC12
      gene was 8.8. The results of FQ-PCR showed that the medians of the log (ZCCHC12
      RNA/GAPDH RNA) in PTC and NG were 0.73 and -1.68, respectively, and the
      difference between them was significant (P < 0.05). There were no significant
      correlations between the RNA levels of the ZCCHC12 gene and the
      clinicopathological and biochemical parameters of PTC in our pilot study. This
      study showed that a number of differentially expressed genes were discovered
      between PTC and NG. Significantly, the number of transcript copies of the ZCCHC12
      gene in PTC was higher than in NG. The verified results of FQ-PCR were consistent
      with the microarray screening results. The ZCCHC12 gene may be a novel diagnostic
      molecular marker of PTC.

PMID- 21739308
TI  - Biochemical characterization of allantoinase from Escherichia coli BL21.
AB  - Bacterial allantoinase (ALLase; EC 3.5.2.5), which catalyzes the conversion of
      allantoin into allantoate, possesses a binuclear metal center in which two metal
      ions are bridged by a posttranslationally carboxylated lysine. Here, we
      characterized ALLase from Escherichia coli BL21. Purified recombinant ALLase
      exhibited no activity but could be activated when preincubating with some metal
      ions before analyzing its activity, and was in the order: Mn(2+)- ? Co(2+)- >
      Zn(2+)- > Ni(2+)- > Cd(2+)- ~Mg(2+)-activated enzyme; however, activity of ALLase
      (Mn(2+)-activated form) was also significantly inhibited with 5 mM Co(2+),
      Zn(2+), and Cd(2+) ions. Activity of Mn(2+)-activated ALLase was increased by
      adding the reducing agent dithiothreitol (DTT), but was decreased by treating
      with the sulfhydryl modifying reagent N-ethylmaleimide (NEM). Inhibition of
      Mn(2+)-activated ALLase by chelator 8-hydroxy-5-quinolinesulfonic acid (8-HQSA),
      but not EDTA, was pH-dependent. Analysis of purified ALLase by gel filtration
      chromatography revealed a mixture of monomers, dimers, and tetramers.
      Substituting the putative metal binding residues His59, His61, Lys146, His186,
      His242, and Asp315 with Ala completely abolished the activity of ALLase, even
      preincubating with Mn(2+) ions. On the basis of these results, as well as the pH
      activity profile, the reaction mechanism of ALLase is discussed and compared with
      those of other cyclic amidohydrolases.

PMID- 21739309
TI  - Curcumin-loaded into PLGA nanoparticles: preparation and in vitro
      schistosomicidal activity.
AB  - The incorporation of the curcumin into poly(lactic-co-glycolic)acid (PLGA)
      nanospheres by the nanoprecipitation technique, the characterization of the
      nanoparticles and the schistosomicidal activity of the curcumin-loaded into PLGA
      nanospheres were reported. The incorporation process occurred with high
      efficiency and the images of field-emission scanning electron microscopy (FESEM)
      revealed the production of spherically shaped particles. According to the dynamic
      light scattering measurements, the particles are nanometric and monodisperse. The
      curcumin-loaded PLGA nanoparticles (50 and 100 MUM) caused the death of all worms
      and a separation between 50% and 100% of Schistosoma mansoni couples at
      concentrations from 30 MUM. Moreover, the curcumin-loaded PLGA nanoparticles also
      decreased the motor activity and caused partial alterations in the tegument of
      adult worms. This study marks the first time that schistosomicidal activity has
      been reported for curcumin-loaded PLGA nanoparticles.

PMID- 21739310
TI  - Comparison of methods for detection of Toxoplasma gondii in tissues of naturally
      exposed pigs.
AB  - This study aimed to compare the sensitivity of five diagnostic methods commonly
      used for the detection of Toxoplasma gondii in tissues of naturally infected
      pigs. We purchased 20 heads of pigs in butcher shops in the city of Ilheus,
      Bahia. Brain and tongue fragments were taken from each animal for the performance
      of PCR against T. gondii. The rest of these two tissues were processed and
      inoculated into three mice. These rodents were observed for 42 days and
      euthanized. We prepared slides with brain and lungs of each mouse for the
      visualization of T. gondii. From the tissues of mice, we carried out polymerase
      chain reaction (PCR), histopathology, and immunohistochemistry in an attempt to
      identify the parasite. The PCR direct from the tissue of pigs showed 10% (2/20)
      of positive samples, all from the brain. PCR in tissue from mice found that 55%
      (11/20) of pigs were positive: 55% (11/20) and 45% (9/20) for brains and tongues,
      respectively. Mice were inoculated with material obtained from the samples and
      examined by various methods for resulting Toxoplasma infection (bioassay). Cyst
      detection in bioassay mice identified 25% (5/20) and immunohistochemistry 30%
      (6/20) of the samples pigs as positive for T. gondii. Histopathology of mice
      tissue could not detect parasite; only suggestive pathological changes such as
      inflammation with foci of necrosis were seen. The results indicated PCR of mice
      tissue as the most sensitive among those tested.

PMID- 21739311
TI  - Prevalence of Trypanosoma sp. in cattle from Tanzania estimated by conventional
      PCR and loop-mediated isothermal amplification (LAMP).
AB  - This study compared the prevalence of trypanosome infections estimated by PFR
      loop-mediated isothermal amplification (LAMP) with conventional polymerase chain
      reaction (PCR) tests. One hundred forty eight cattle blood samples were collected
      from Robanda village, Mara region, Tanzania in April 2008. In conventional PCR,
      four sets of primers, specific for the detection of Trypanosoma sp., Trypanosoma
      brucei rhodesiense, Trypanosoma vivax, and Trypanozoon, as well as a modified
      LAMP were used. Conventional PCR detected no infection or up to 8, 1, and 3
      infections with Trypanosoma congolense savannah, Trypanozoon, and T. vivax,
      respectively, whereas LAMP detected additional 44 Trypanozoon positive cases. Our
      results clearly indicate that the prevalence of Trypanozoon spp. in cattle in
      Robanda village estimated by PFR-LAMP (30.4%) was significantly higher than the
      estimates by PCR assays (0.6-2%). As such, future studies should target
      epidemiological surveys of Trypanozoon and T. brucei rhodesiense infections in
      possible reservoir animals by LAMP to further elucidate the actual prevalence of
      these parasites.

PMID- 21739312
TI  - Infection level of the Asian tapeworm (Bothriocephalus acheilognathi) in the
      cyprinid fish, Schizothorax niger, from Anchar Lake, relative to season, sex,
      length and condition factor.
AB  - Various studies have shown that the Asian fish tapeworm, Bothriocephalus
      acheilognathi causes great economic loss in hatcheries, fish farms as well as in
      lakes. In order to understand the seasonal variation of infection in a nutrient
      enriched lake, parasitological investigation was carried out in the indigenous
      cyprinid fish, Schizothorax niger Heckel 1838 from September, 2008 to August,
      2009. Overall, this study revealed definite seasonality of infection (p < 0.05),
      with greater infection in summer (prevalence = 39.5%) and lesser in winter
      (prevalence = 8.1%). The prevalence among different seasons revealed significant
      differences (p < 0.05). Sex was not an important factor influencing the
      prevalence of the Asian tapeworm. A strong positive correlation (Pearson's
      correlation, r = 0.7; p = 0.02) between total length of S. niger and number of
      Asian fish tapeworms was observed. Similarly, a strong positive correlation
      existed between weight of fish and number of tapeworms (Pearson's correlation, r
      = 0.7; p = 0.005). Prevalence and mean abundance were positively and
      significantly correlated with water temperature (r = 0.8, p < 0.01 and r = 0.8, p
      < 0.01, respectively). Thus seasonal dynamics, total length and weight of the
      host significantly influenced the tapeworm infection. The above findings will be
      useful in devising the appropriate control strategies for the Asian tapeworm in
      wild fish in Kashmir valley as well as in similar climatic zones of other parts
      of the world. Also, information from this study will be used to assess the spread
      and extent of B. acheilognathi which is a potential threat to the indigenous fish
      fauna of Anchar Lake.

PMID- 21739313
TI  - Characterization and vaccination of two novel Schistosoma japonicum genes
      screened from a cercaria cDNA library.
AB  - Two novel genes, SJCWL05 and SJCWL06, were harvested from screening of
      Schistosoma japonicum (S. japonicum) cercaria cDNA library by using pig sera
      vaccinated (VPS) with S. japonicum immature egg ws-vaccine (S. japonicum iEw).
      Prokaryotic recombinant plasmids pGEX-4T-1/SJCWL05 and pGEX-4T-1/SJCWL06 were
      constructed to analyze their immunogenicity, which was confirmed by SDS-PAGE and
      Western blotting. Two eukaryotic recombinant plasmids, pcDNA3/SJCWL05 and
      pcDNA3/SJCWL06, were constructed, and their ability to protect mice against
      challenge of S. japonicum was evaluated. All mice vaccinated with pcDNA3/SJCWL05
      or pcDNA3/SJCWL06 developed ELISA-specific anti-S. japonicum SIEA (S. japonicum
      soluble immature egg antigens) antibody. Immunoprotection experiments showed that
      worms and liver eggs reduced 34.64% and 39.14% in the pcDNA3/SJCWL05 group and
      those reduced 27.17% and 27.95% in the pcDNA3/SJCWL06 group, respectively. The
      reduction rates of intestine and uterine eggs in female worms of both groups
      reached 39.45% and 38.5% as well as 30.02% and 28.7%, respectively. Results of
      our study suggest that novel genes, SJCWL05 and SJCWL06, are potential vaccine
      candidates against schistosomiasis japonica.

PMID- 21739314
TI  - Immune protection of Mozambique tilapia (Oreochromis mossambicus) exposed to
      different infectious doses of ectoparasite (Cryptocaryon irritans).
AB  - The objectives of the present study were to standardize a reproducible infection
      procedure with Cryptocaryon irritans and to examine the effects of infectious
      dose level on the immune protection in Mozambique tilapia (Oreochromis
      mossambicus). This study demonstrated that direct enumeration of trophonts on the
      pectoral fin was useful to quantitatively assess immune protection against C.
      irritans. The number of trophonts on a pectoral fin was positively correlated
      with infectious dose of live theronts. Fish immunized by direct exposure under
      controlled laboratory conditions allowed for in depth examination of the effects
      of the degree of infectious dose on immune response. There was no significant
      positive correlation between the initial infectious dose and degree of immune
      responses. Mozambique tilapia initiated a strong immune protection by direct
      exposure with even a small number of parasites (e.g. 300 theronts per fish).
      Moreover, as the result of the protein analysis, we identified 28 kD proteins
      that could be responsible for the immobilizing antigen.

PMID- 21739316
TI  - In vitro sensitivity of Plasmodium falciparum field isolates to extracts from
      Cameroonian Annonaceae plants.
AB  - In a search for new plant-derived antimalarial extracts, 19 fractions were
      obtained from three Annonaceae species, Uvariopsis congolana (leaf, stem),
      Polyalthia oliveri (stem bark), and Enantia chlorantha (stem, stem bark) with
      yields ranging from 0.33% to 4.60%. The extracts were prepared from 500 g of each
      plant part, using organic solvents to afford five methanolic fractions
      (acetogenin rich), five water fractions, five hexane fractions, and four
      interface precipitates. Evaluation of the activity of fractions in vitro against
      field isolates of the malaria parasite Plasmodium falciparum showed that
      acetogenin-rich fractions and interface precipitates were the most potent, with
      IC(50) values ranging from 0.05 to 8.09 MUg/ml. Sensitivity of parasite isolates
      to plant extracts varied greatly, with over 100-fold difference from isolate to
      isolate in some cases. The active acetogenin-rich fractions and interface
      precipitates were assessed in combination with chloroquine in the same
      conditions, and showed additive interaction in the huge majority of cases.
      Synergistic interactions were found in some cases with acetogenin-rich fractions.
      Acute toxicity of promising fractions was evaluated through oral administration
      in Swiss albino mice. Tested fractions appeared to be safe, with LD(50) values
      higher than 2 g/kg. In summary, acetogenin-rich fractions from Annonaceae species
      showed high potency against P. falciparum field isolates and safety by oral
      administration in mice, supporting their detailed investigation for antimalarial
      drug discovery.

PMID- 21739317
TI  - Postoperative pancreatic fistula and the risk factors of laparoscopy-assisted
      distal gastrectomy for early gastric cancer.
AB  - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) was introduced as
      minimally invasive surgery for early gastric cancer (EGC) in Japan. This study
      investigated postoperative pancreatic fistula (POPF) and associated risk factors
      of the procedure. METHODS: From January 2005 to December 2009, 798 patients with
      EGC diagnosed before surgery underwent LADG. Thirty-four patients developed
      postoperative pancreatic fistula (POPF group), whereas the other 764 patients did
      not experience POPF (NPOPF group). POPF was defined and graded according to the
      International Study Group on Pancreatic Fistula Definition (ISGPF). Patient
      characteristics and operative and postoperative outcomes were compared between
      the two groups. Risk factors associated with POPF were analyzed. RESULTS: POPF
      occurred in 34 (4.3%) patients; among them 3 developed grade C POPF, a
      complication that required aggressive clinical intervention, and only 1 underwent
      reoperation. Compared with the NPOPF group, the POPF group had higher percentage
      of male patients (88.2% vs. 60.5%, P = 0.001), higher mean body mass index (24.8
      +/- 2.5 kg/m(2) vs. 22.5 +/- 3.2 kg/m(2), P < 0.001), longer mean operation time
      (251.3 +/- 46.7 min vs. 229.7 +/- 53.9 min, P = 0.022), higher postoperative
      complications (100% vs. 8.6%, P < 0.001), and longer mean postoperative hospital
      stay (29.6 +/- 19.9 days vs. 12.6 +/- 6.7 days, P < 0.001). Univariate and
      multivariate analysis identified sex and body mass index as risk factors
      associated with POPF after LADG. CONCLUSIONS: LADG can be performed safely in
      patients with EGC in terms of the low incidence of POPF. To decrease the risk of
      POPF, LADG should be performed cautiously in male patients with high body mass
      index.

PMID- 21739318
TI  - MRI versus breast-specific gamma imaging (BSGI) in newly diagnosed ductal cell
      carcinoma-in-situ: a prospective head-to-head trial.
AB  - BACKGROUND: Mammography remains the standard imaging technique for the diagnosis
      of ductal carcinoma-in-situ (DCIS). Functional breast imaging, including breast
      magnetic resonance imaging (MRI), has known limitations in evaluating DCIS. To
      date, there are limited data on the utility of breast-specific gamma imaging
      (BSGI) in DCIS. We sought to prospectively compare the sensitivity of BSGI to MRI
      in newly diagnosed DCIS patients. METHODS: Patients with newly diagnosed DCIS
      from June 1, 2009, through May 31, 2010, underwent a protocol with both breast
      MRI and BSGI. Each imaging study was read by a separate dedicated breast
      radiologist. Patients were excluded if excisional biopsy was performed for
      diagnosis, if their MRI was performed at an outside facility, or if final
      pathology revealed invasive carcinoma. RESULTS: There were 18 patients enrolled
      onto the study that had both MRI and BSGI for newly diagnosed DCIS. The
      sensitivity for MRI was 94% and for BSGI was 89% (P > 0.5, NS). There was one
      index tumor not seen on either MRI or BSGI, and one index tumor seen on MRI but
      not visualized on BSGI. DISCUSSION: Although BSGI has previously been shown to be
      as sensitive as MRI for detecting known invasive breast carcinoma, this study
      shows that BSGI is equally as sensitive as MRI at detecting newly diagnosed DCIS.
      As a result of the limited number of patients enrolled onto the study, larger
      prospective studies need to be performed to determine the true sensitivity and
      specificity of BSGI.

PMID- 21739319
TI  - Enhanced light-activated RNA interference using phosphorothioate-based dsRNA
      precursors of siRNA.
AB  - PURPOSE: To improve light-activated RNA interference by incorporating
      phosphorothioate linkages into the dsRNA used. The rationale behind this approach
      is that the groups have the potential to improve nuclease stability and therefore
      prevent cleavage of photolabile groups from the RNA termini prior to photolysis.
      METHODS: Photolabile groups (di-methoxy nitro phenyl ethyl or DMNPE) were
      incorporated into multiple double-stranded precursors of siRNA (dsRNA) that had
      six, two or no phosphorothioate linkages at the 3' and 5' ends of the strands.
      They were analyzed for their ability to toggle light-activated RNA interference
      with light and for serum stability. RESULTS: Incorporation of phosphorothioate
      linkages increased serum stability of all dsRNA examined. Presence of DMNPE
      groups reduced overall stability of the modified RNA relative to the analogous
      species without DMNPE modification. DMNPE-modified dsRNA with two
      phosphorothioate linkages in each strand significantly improved the window of
      expression toggled by light. CONCLUSIONS: Incorporating phosphorothioate groups
      into dsRNA both stabilizes them towards degradation by serum enzymes, as well as
      improves them as the basis for light-activated RNA interference.

PMID- 21739320
TI  - Trial and error: how the unclonable human mitochondrial genome was cloned in
      yeast.
AB  - PURPOSE: Development of a human mitochondrial gene delivery vector is a critical
      step in the ability to treat diseases arising from mutations in mitochondrial
      DNA. Although we have previously cloned the mouse mitochondrial genome in its
      entirety and developed it as a mitochondrial gene therapy vector, the human
      mitochondrial genome has been dubbed unclonable in E. coli, due to regions of
      instability in the D-loop and tRNA(Thr) gene. METHODS: We tested multi- and
      single-copy vector systems for cloning human mitochondrial DNA in E. coli and
      Saccharomyces cerevisiae, including transformation-associated recombination.
      RESULTS: Human mitochondrial DNA is unclonable in E. coli and cannot be retained
      in multi- or single-copy vectors under any conditions. It was, however, possible
      to clone and stably maintain the entire human mitochondrial genome in yeast as
      long as a single-copy centromeric plasmid was used. D-loop and tRNA(Thr) were
      both stable and unmutated. CONCLUSIONS: This is the first report of cloning the
      entire human mitochondrial genome and the first step in developing a gene
      delivery vehicle for human mitochondrial gene therapy.

PMID- 21739321
TI  - Encapsulation and release of Amphotericin B from an ABC triblock fluorous
      copolymer.
AB  - PURPOSE: PEG-phospholipid-based micelles have been successfully used for the
      solubilization of several hydrophobic drugs but generally lack sustained
      stability in blood. Our novel PEG-Fluorocarbon-DSPE polymers were designed to
      increase stability and improve time-release properties of drug-loaded micelles.
      METHODS: Novel ABC fluorous copolymers were synthesized, characterized, and used
      for encapsulation release of amphotericin B. FRET studies were used to study
      micelle stability. RESULTS: The micelles formed by the new polymers showed lower
      critical micelle concentrations and higher viscosity cores than those formed by
      the polymers lacking the fluorous block. FRET studies indicated that fluorocarbon
      containing micelles had increased stability in presence of human serum.
      Physicochemical properties and in vitro release profile of micelles loaded with
      Amphotericin B (AmB) were studied. CONCLUSIONS: The effect of PEG length and
      fluorocarbon incorporation were investigated. The shorter hydrophilic PEG2K
      induced greater stability than PEG5K by decreasing the proportion of hydrophilic
      block of the polymer. The fluorocarbon placed between hydrophilic and hydrophobic
      block formed a fluorous shell contributing to the enhanced thermodynamic
      stability of micelles and to the drug sustained release. Polymer mPEG2K-F(10)
      DSPE, bearing both a fluorocarbon block and a shorter mPEG, showed the greatest
      stability and the longest half-life for AmB release.

PMID- 21739322
TI  - All-polyethylene tibial components in obese patients are associated with low
      failure at midterm followup.
AB  - BACKGROUND: In the United States, the obese population has increased markedly
      over the last four decades, and this trend continues. High patient weight places
      additional stress on TKA components, which may lead to increased polyethylene
      wear, osteolysis, radiolucencies, and clinical failure. Metal-backed tibial
      components and all-polyethylene tibial components in the general population have
      comparable osteolysis and failure, but it is unclear whether these components
      yield similar osteolysis and failure in obese patients. QUESTIONS/PURPOSES: We
      therefore determined the (1) function, (2) occurrence of osteolysis, and (3)
      complications in a cohort of obese patients receiving all-polyethylene tibial
      components. PATIENTS AND METHODS: Between September 17, 1996, and December 19,
      2002, we implanted all-polyethylene tibial components in 90 obese patients (125
      knees); 24 patients (33 knees) died and 13 patients (17 knees) were lost to
      followup, leaving 53 patients (59%) with 75 knees. All surgeries were cruciate
      retaining, tricompartmental TKAs. We evaluated patients with Knee Society Scores
      and serial radiographs. Minimum followup was 7 years (mean, 10.4 years; range, 7
      14 years). RESULTS: At latest followup, mean Knee Society Score was 92 points.
      There were five tibial radiolucencies, all less than 1 mm and characterized as
      nonprogressive. We observed minimal, nonprogressive osteolysis in one knee. One
      patient required reoperation after a traumatic event. There were no implant
      related failures and no implants at risk of failure. CONCLUSIONS: At an average
      10-year followup, all-polyethylene tibial components were functioning well in
      this obese group. These findings confirm the effectiveness of all-polyethylene
      tibial components in obese patients.

PMID- 21739323
TI  - Revision ACL reconstruction in skeletally mature athletes younger than 18 years.
AB  - BACKGROUND: Young, active, skeletally mature patients have higher failure rates
      after various surgical procedures, including stabilization for shoulder
      instability and primary ACL reconstruction. It is unclear whether young, active,
      skeletally mature patients share similarly high failure rates after revision ACL
      reconstruction. QUESTIONS/PURPOSES: We therefore determined whether revision ACL
      reconstruction restores knee stability and allows young (younger than 18 years),
      active, skeletally mature patients to return to preinjury activity levels.
      PATIENTS AND METHODS: We retrospectively identified 36 patients who had an
      initial ACL reconstruction between the ages of 12 and 17 years (mean, 15.4 years)
      and subsequent revision between the ages of 13 and 18 years (mean, 16.9 years);
      of these, 2-year followup was available for 21 (75%). Mechanisms of primary graft
      failure included traumatic rerupture (23 noncontact, seven contact), persistent
      instability (five), and infection (one). One patient had open physes at the time
      of revision. All revisions were single-stage transosseous reconstructions. The
      minimum followup was 24 months (mean, 36 months; range, 24-63 months). RESULTS:
      At last followup, 19 of 21 patients had a negative or IA Lachman and 20 of 21 had
      a negative pivot shift. Mean International Knee Documentation Committee
      subjective score was 89 (range, 64-99). Eleven of the 21 patients returned to the
      same or higher activity/sport level as before their original injury. Two patients
      reported subjective knee instability, with two having repeat revision
      reconstruction for failure. CONCLUSIONS: Single-stage transosseous revision ACL
      reconstruction in young, active, skeletally mature patients restores knee
      stability but returns only 52% of patients to their prior level of activity or
      sport. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 21739325
TI  - Labial fusion causing urinary incontinence: comment.

PMID- 21739326
TI  - Treatment of acute radiation cystitis: comment.

PMID- 21739328
TI  - The psychometric validation of a 1-week recall period for the OAB-q.
AB  - INTRODUCTION AND HYPOTHESIS: As shorter recall periods are sometimes preferable
      to longer recall periods, the objective of this study was to evaluate the
      psychometric characteristics and measurement properties of the 1-week recall
      version of the Overactive Bladder Questionnaire (OAB-q). METHODS: Secondary
      analyses were performed on data for three 12-week clinical trials of
      fesoterodine. Patients completed the Patient Perception of Bladder Condition
      (PPBC), the Patient Perception of Urgency Scale (PPUS), and 3-day bladder diaries
      in addition to the OAB-q at baseline, 4 and 12 weeks. Analyses were conducted to
      evaluate the reliability, concurrent and discriminant validity and responsiveness
      of the OAB-q 1-week recall version. RESULTS: The patients in the three studies
      (Study 1: N=516, Study 2: N=441; Study 3: N=882) had a mean age of 59.6, 59.4,
      and 59.9 years, respectively; and most of the patients were female (77.1%, 88.9%,
      and 82.9%) and White (76.6%, 90.0%, and 88.0%). Patients had been diagnosed with
      OAB for a mean of 5.2, 8.3, and 9.1 years, respectively. Cronbach's alpha values
      were greater than 0.85 across all samples and subscales. Correlations between the
      1-week recall version of the OAB-q and the PPBC, PPUS, and most of the bladder
      diary variables were moderate to strong. Discriminant validity of the OAB-q was
      good, with significant differences in mean OAB-q scores across all response
      categories of the PPUS. The OAB-q was highly responsive to changes in patients'
      conditions as indicated by moderate to large effect sizes. The OAB-q 1-week
      recall version has a similar factor structure to the 4-week recall version with
      each subscale model demonstrating acceptable fit. CONCLUSION: The 1-week recall
      version of the OAB-q appears to be reliable, valid, and responsive and is
      psychometrically equivalent to the 4-week recall version. The validation of the 1
      week recall version offers researchers and clinicians an additional option for
      using the OAB-q.

PMID- 21739329
TI  - Biventricular assist devices: a technical review.
AB  - The optimal treatment option for end stage heart failure is transplantation;
      however, the shortage of donor organs necessitates alternative treatment
      strategies such as mechanical circulatory assistance. Ventricular assist devices
      (VADs) are employed to support these cases while awaiting cardiac recovery or
      transplantation, or in some cases as destination therapy. While left ventricular
      assist device (LVAD) therapy alone is effective in many instances, up to 50% of
      LVAD recipients demonstrate clinically significant postoperative right
      ventricular failure and potentially need a biventricular assist device (BiVAD).
      In these cases, the BiVAD can effectively support both sides of the failing
      heart. This article presents a technical review of BiVADs, both clinically
      applied and under development. The BiVADs which have been used clinically are
      predominantly first generation, pulsatile, and paracorporeal systems that are
      bulky and prone to device failure, thrombus formation, and infection. While they
      have saved many lives, they generally necessitate a large external pneumatic
      driver which inhibits normal movement and quality of life for many patients. In
      an attempt to alleviate these issues, several smaller, implantable second and
      third generation devices that use either immersed mechanical blood bearings or
      hydrodynamic/magnetic levitation systems to support a rotating impeller are under
      development or in the early stages of clinical use. Although these rotary devices
      may offer a longer term, completely implantable option for patients with
      biventricular failure, their control strategies need to be refined to compete
      with the inherent volume balancing ability of the first generation devices. The
      BiVAD systems potentially offer an improved quality of life to patients with
      total heart failure, and thus a viable alternative to heart transplantation is
      anticipated with continued development.

PMID- 21739330
TI  - Reduced myocardial 18F-FDG uptake after calcium channel blocker administration.
      Initial observation for a potential new method to improve plaque detection.
AB  - PURPOSE: Physiological glucose uptake by the myocardium may hamper visualization
      of coronary atherosclerotic plaques in (18)F-FDG PET studies. Intracellular
      myocardial calcium relates to glucose influx. We assessed whether administration
      of a calcium channel blocker such as verapamil could decrease myocardial (18)F
      FDG uptake in mice. METHODS: Experiments were conducted on ten male
      C57BL/6JOlaHsd mice. The mice were studied by (18)F-FDG PET/CT under basal
      conditions and after a single administration of verapamil injected 1 h prior to
      (18)F-FDG administration at doses of 1 mg/kg (group A, n = 5) and 20 mg/kg (group
      B, n = 5). PET scanning was started 60 min after injection of (18)F-FDG employing
      a dedicated small-animal PET/CT system (ARGUS-CT). In each mouse, post-verapamil
      PET images were coregistered with the basal PET images. Volumetric regions of
      interest (VOI) were drawn on the basal study containing the myocardium of the
      whole left ventricle and quantitatively compared with the same VOI applied to the
      post-verapamil scan. The SUV(mean) was used to express the mean myocardial (18)F
      FDG uptake. The relative coefficient of variation (RV) between the basal and post
      verapamil conditions was calculated. RESULTS: Verapamil administration decreased
      myocardial (18)F-FDG uptake in all animals. The median (range) SUV(mean) values
      in group A were 2.6 (1.6-4.1) under basal conditions and 1.7 (1.1-2.9) after
      verapamil administration (p = 0.043), and in group B were 1.6 (1.3-2.0) under
      basal conditions and 1.0 (0.9-1.4) after verapamil administration (p = 0.043).
      The median (range) RV values were -31% (-5%, -50%) in group A, and -37% (-10%, 
      51%) in group B (p = 0.6). CONCLUSION: In this animal model there was a
      significant reduction in (18)F-FDG uptake in the myocardium following verapamil
      administration. This type of intervention could facilitate the definition of
      coronary atherosclerotic plaque inflammation on (18)F-FDG PET scans.

PMID- 21739331
TI  - Diagnosis and dosimetry in differentiated thyroid carcinoma using 124I PET:
      comparison of PET/MRI vs PET/CT of the neck.
AB  - PURPOSE: This study compares intrinsically coregistered 124I positron emission
      tomography (PET) and CT (PET/CT) and software coregistered 124I PET and MRI
      (PET/MRI) images for the diagnosis and dosimetry of thyroid remnant tissues and
      lymph node metastases in patients with differentiated thyroid carcinoma (DTC).
      METHODS: After thyroidectomy, 33 high-risk DTC patients (stage III or higher)
      received 124I PET/CT dosimetry prior to radioiodine therapy to estimate the
      absorbed dose to lesions and subsequently underwent a contrast-enhanced MRI
      examination of the neck. Images were evaluated by two experienced nuclear
      medicine physicians and two radiologists to identify the lesions and to
      categorize their presumable provenience, i.e. thyroid remnant tissue (TT), lymph
      node metastasis (LN) and inconclusive tissue. The categorization and dosimetry of
      lesions was initially performed with PET images alone (PET only). Subsequently
      lesions were reassessed including the CT and MRI data. RESULTS: The analyses were
      performed on a patient and on a lesion basis. Patient-based analyses showed that
      26 of 33 (79%) patients had at least one lesion categorized as TT on PET only. Of
      these patients, 11 (42%) and 16 (62%) had a morphological correlate on CT and
      MRI, respectively, in at least one TT PET lesion. Twelve patients (36%) had at
      least one lesion classified as LN on PET only. Nine (75%) of these patients had a
      morphological correlate on both CT and MRI in at least one LN PET lesion. Ten
      patients (30%) showed at least one lesion on PET only classified as inconclusive.
      The classification was changed to a clear classification in two patients (two LN)
      by CT and in four (two TT, two LN) patients by MRI. Lesion-based analyses (n=105
      PET positive lesions) resulted in categorization as TT in 61 cases (58%), 16
      (26%) of which had a morphological correlate on CT and 33 (54%) on MRI. A total
      of 29 lesions (27%) were classified as LN on PET, 18 (62%) of which had a
      morphological correlate on CT and 24 (83%) on MRI. In 16 lesions (15%) PET alone
      allowed no definite categorization. Categorization was achieved with the aid of
      CT and MRI, respectively, in five (one TT, four LN) and in six (two TT, four LN)
      lesions. In direct comparison, 23 lesions were not discernible on CT but clearly
      visible on MRI, 15 of which were smaller than 10 mm and about two thirds were
      classified as TT. Redoing dosimetry based on the volume information from MRI for
      these small lesions would have changed the initial therapy regime in five
      patients. These patients would have received (131)I therapy with standardized
      activities of 3.7 GBq or 7.4 GBq instead of activities higher than 10 GBq and
      would have benefited from reduced radiation exposure. CONCLUSION: PET/MRI is
      superior to PET/CT in terms of tracing back a PET focus to a morphological
      correlate. For this reason PET/MRI enhances diagnostic certainty for lesions<10
      mm and improves pretherapeutic lesion dosimetry in DTC.

PMID- 21739332
TI  - A retrospective analysis of delayed complications of urethroplasty at a tertiary
      care centre.
AB  - Urethroplasty is commonly performed worldwide by reconstructive urologists and
      such a large scale practice is often faced with numerous complications, yet
      "complication based analysis" still persists as a gray area. Our study aims to
      provide an evaluation of long-term post-urethroplasty complications, after the
      five commonly practiced procedures, at our centre. 302 male patients with
      urethral strictures due to various etiologies were assessed preoperatively via
      retrograde urethrogram, urethrosonogram, and uroflowmetry. They were then
      subjected to different urethroplasty techniques viz. tunica albuginea
      urethroplasty (TAU), U-shaped prostato-bulbar anastomosis (USPBA), dorsal buccal
      mucosa graft urethroplasty, skin substitution urethroplasty and Dartos flap
      urethroplasty. Postoperatively, patients were assessed at regular intervals,
      regarding the occurrence of complications. The overall complication rate was 21%
      at 5 years follow-up, with the majority during the initial 2 years. Infection and
      restenosis were the major long-term complications (12%). Maximum complications
      were seen in patients, who underwent TAU and USPBA simultaneously followed by
      Dartos flap urethroplasty and minimum were seen with TAU. In conclusion, a
      meticulous post-urethroplasty follow-up reveals a wide range of long-term
      complications. The complication rate differs in accordance with the etiology,
      site and length of stricture as well as the reconstructive technique.

PMID- 21739333
TI  - Combined use of in vitro phototoxic assessments and cassette dosing
      pharmacokinetic study for phototoxicity characterization of fluoroquinolones.
AB  - The present study aimed to develop an effective screening strategy to predict in
      vivo phototoxicity of multiple compounds by combined use of in vitro
      phototoxicity assessments and cassette dosing pharmacokinetic (PK) studies.
      Photochemical properties of six fluoroquinolones (FQs) were evaluated by UV
      spectral and reactive oxygen species (ROS) assays, and phototoxic potentials of
      FQs were also assessed using 3T3 neutral red uptake phototoxicity test (3T3 NRU
      PT) and intercalator-based photogenotoxicity (IBP) assay. Cassette dosing
      pharmacokinetics on FQs was conducted for calculating PK parameters and dermal
      distribution. All the FQs exhibited potent UV/VIS absorption and ROS generation
      under light exposure, suggesting potent photosensitivity of FQs. In vitro
      phototoxic risks of some FQs were also elucidated by 3T3 NRU PT and IBP assay.
      Decision matrix for phototoxicity prediction was built upon these in vitro data,
      taken together with outcomes from cassette dosing PK studies. According to the
      decision matrix, most FQs were deduced to be phototoxic, although gatifloxacin
      was found to be less phototoxic. These findings were in agreement with clinical
      observations. Combined use of in vitro photobiochemical and cassette dosing PK
      data will be useful for predicting in vivo phototoxic potentials of drug
      candidates with high productivity and reliability.

PMID- 21739334
TI  - Favourable cost-benefit in an early defibrillation programme using dual dispatch
      of ambulance and fire services in out-of-hospital cardiac arrest.
AB  - AIMS: Out-of-hospital cardiac arrest is fatal without treatment, and time to
      defibrillation is an extremely important factor in relation to survival. We
      performed a cost-benefit analysis of dual dispatch defibrillation by ambulance
      and fire services in the County of Stockholm, Sweden. METHODS AND RESULTS: A cost
      benefit analysis was performed to evaluate the effects of dual dispatch
      defibrillation. The increased survival rates were estimated from a real-world
      implemented intervention, and the monetary value of a life (<euro> 2.2 million)
      was applied to this benefit by using results from a recent stated-preference
      study. The estimated costs include defibrillators (including
      expendables/maintenance), training, hospitalisation/health care, fire service
      call-outs, overhead resources and the dispatch centre. The estimated number of
      additional saved lives was 16 per year, yielding a benefit-cost ratio of 36. The
      cost per quality-adjusted life years (QALY) was estimated to be <euro> 13,000,
      and the cost per saved life was <euro> 60,000. CONCLUSIONS: The intervention of
      dual dispatch defibrillation by ambulance and fire services in the County of
      Stockholm had positive economic effects. For the cost-benefit analysis, the
      return on investment was high and the cost-effectiveness showed levels below the
      threshold value for economic efficiency used in Sweden. The cost-utility analysis
      categorises the cost per QALY as medium.

PMID- 21739335
TI  - Sampling HIV intrahost genealogies based on a model of acute stage CTL response.
AB  - Cytotoxic T lymphocytes (CTLs) play an important role in the immune response to
      HIV during the acute stage of infection, but the effect of CTLs on HIV intrahost
      genetic diversity is poorly understood. We introduce a model of CTL attack during
      the acute stage. Assuming this model, we develop a method to sample HIV intrahost
      genealogies. Using our sampling approach, we characterize the evolutionary forces
      that shape HIV genealogies. In particular, we show that early mutation events can
      have significant impact on HIV genealogies and that certain types of CTL attack
      are best at controlling HIV genetic diversity. Our sampler represents a first
      step toward using HIV genetic data to infer properties of CTL attack.

PMID- 21739336
TI  - Porcine major histocompatibility complex (MHC) class I molecules and analysis of
      their peptide-binding specificities.
AB  - In all vertebrate animals, CD8(+) cytotoxic T lymphocytes (CTLs) are controlled
      by major histocompatibility complex class I (MHC-I) molecules. These are highly
      polymorphic peptide receptors selecting and presenting endogenously derived
      epitopes to circulating CTLs. The polymorphism of the MHC effectively
      individualizes the immune response of each member of the species. We have
      recently developed efficient methods to generate recombinant human MHC-I (also
      known as human leukocyte antigen class I, HLA-I) molecules, accompanying peptide
      binding assays and predictors, and HLA tetramers for specific CTL staining and
      manipulation. This has enabled a complete mapping of all HLA-I specificities
      ("the Human MHC Project"). Here, we demonstrate that these approaches can be
      applied to other species. We systematically transferred domains of the frequently
      expressed swine MHC-I molecule, SLA-1*0401, onto a HLA-I molecule (HLA-A*11:01),
      thereby generating recombinant human/swine chimeric MHC-I molecules as well as
      the intact SLA-1*0401 molecule. Biochemical peptide-binding assays and positional
      scanning combinatorial peptide libraries were used to analyze the peptide-binding
      motifs of these molecules. A pan-specific predictor of peptide-MHC-I binding,
      NetMHCpan, which was originally developed to cover the binding specificities of
      all known HLA-I molecules, was successfully used to predict the specificities of
      the SLA-1*0401 molecule as well as the porcine/human chimeric MHC-I molecules.
      These data indicate that it is possible to extend the biochemical and
      bioinformatics tools of the Human MHC Project to other vertebrate species.

PMID- 21739337
TI  - Context and competition in the capture of visual attention.
AB  - Competition-based models of visual attention propose that perceptual ambiguity is
      resolved through inhibition, which is stronger when objects share a greater
      number of neural receptive fields (RFs). According to this theory, the
      misallocation of attention to a salient distractor--that is, the capture of
      attention--can be indexed in RF-scaled interference costs. We used this pattern
      to investigate distractor-related costs in visual search across several
      manipulations of temporal context. Distractor costs are generally larger under
      circumstances in which the distractor can be defined by features that have
      recently characterised the target, suggesting that capture occurs in these
      trials. However, our results show that search for a target in the presence of a
      salient distractor also produces RF-scaled costs when the features defining the
      target and distractor do not vary from trial to trial. Contextual differences in
      distractor costs appear to reflect something other than capture, perhaps a
      qualitative difference in the type of attentional mechanism deployed to the
      distractor.

PMID- 21739338
TI  - New MRI studies support the Blanchard typology of male-to-female transsexualism.

PMID- 21739339
TI  - Processing of a free word order language: the role of syntax and context.
AB  - In languages with flexible constituent order (so-called free word order
      languages), available orders are used to encode given/new distinctions; they
      therefore differ not only syntactically, but also in their context requirements.
      In Experiment 1, using a self-paced reading task, we compared Russian S V IO DO
      (canonical), DO S V IO and DO IO V S constructions in appropriate vs.
      inappropriate contexts (those that violated their context requirements). The
      context factor was significant, while the syntax factor was not. The less
      pronounced context effect evidenced in previous studies (e.g., Kaiser and
      Trueswell in Cognitioin 94:113-147, 2004) might be due to the use of shorter
      target sentences and less extensive contexts. We also demonstrated that the slow
      down starts at the first contextually inappropriate constituent, which shows that
      the information about context requirements is taken into account immediately, but
      that it develops faster on preverbal subjects and postverbal indirect objects
      (occupying their canonical positions) than on preverbal indirect objects
      (occupying a noncanonical position, or scrambled). In Experiment 2, these
      findings were replicated for IO S V DO and IO DO V S orders. S V IO DO orders
      with a continuation were used to show that there is no additional effect of
      inappropriate context at the end of the sentence.

PMID- 21739340
TI  - Effect of tidal volume, intrathoracic pressure, and cardiac contractility on
      variations in pulse pressure, stroke volume, and intrathoracic blood volume.
AB  - PURPOSE: We evaluated the impact of increasing tidal volume (V (t)), decreased
      chest wall compliance, and left ventricular (LV) contractility during
      intermittent positive-pressure ventilation (IPPV) on the relation between pulse
      pressure (PP) and LV stroke volume (SV(LV)) variation (PPV and SVV,
      respectively), and intrathoracic blood volume (ITBV) changes. METHODS: Sixteen
      pentobarbital-anesthetized thoracotomized mongrel dogs were studied both before
      and after propranolol-induced acute ventricular failure (AVF) (n = 4), with and
      without chest and abdominal pneumatic binders to decrease chest wall compliance
      (n = 6), and during V (t) of 5, 10, 15, and 25 ml/kg (n = 6). SV(LV) and right
      ventricular stroke volume (SV(RV)) were derived from electromagnetic flow probes
      around aortic and pulmonary artery roots. Arterial pressure was measured in the
      aorta using a fluid-filled catheter. Arterial PPV and SVV were calculated over
      three breaths as (max - min)/[(max + min)/2]. ITBV changes during ventilation
      were inferred from the beat-to-beat volume differences between SV(RV) and SV(LV).
      RESULTS: Arterial PP and SV(LV) were tightly correlated during IPPV under all
      conditions (r (2) = 0.85). Both PPV and SVV increased progressively as V (t)
      increased and with thoraco-abdominal binding, and tended to decrease during AVF.
      SV(RV) phasically decreased during inspiration, whereas SV(LV) phasically
      decreased 2-3 beats later, such that ITBV decreased during inspiration and
      returned to apneic values during expiration. ITBV decrements increased with
      increasing V (t) or with thoraco-abdominal binding, and decreased during AVF
      owing to variations in SV(RV), such that both PPV and SVV tightly correlated with
      inspiration-associated changes in SV(RV) and ITBV. CONCLUSION: Arterial PP and
      SV(LV) are tightly correlated during IPPV and their relation is not altered by
      selective changes in LV contractility, intrathoracic pressure, or V (t). However,
      contractility, intrathoracic pressure, and V (t) directly alter the magnitude of
      PPV and SVV primarily by altering the inspiration-associated decreases in SV(RV)
      and ITBV.

PMID- 21739341
TI  - Does femoral venous pressure measurement correlate well with intrabladder
      pressure measurement? A multicenter observational trial.
AB  - PURPOSE: To investigate if femoral venous pressure (FVP) measurement can be used
      as a surrogate measure for intra-abdominal pressure (IAP) via the bladder.
      METHODS: This was a prospective, multicenter observational study. IAP and FVP
      were simultaneously measured in 149 patients. The effect of BMI on IAP was
      investigated. RESULTS: The incidences of intra-abdominal hypertension (IAH) and
      abdominal compartment syndrome (ACS) were 58 and 7% respectively. The mean APACHE
      II score was 22 +/- 10, SAPS 2 score 42 +/- 20, and SOFA score 9 +/- 4. The mean
      IAP was 11.2 +/- 4.5 mmHg versus 12.7 +/- 4.7 mmHg for FVP. The bias and
      precision for all measurements were -1.5 and 3.6 mmHg respectively with the lower
      and upper limits of agreement being -8.6 and 5.7. When IAP was above 20 mmHg, the
      bias between IAP and FVP was 0.7 with a precision of 2.0 mmHg (lower and upper
      limits of agreement -3 and 4.6 respectively). Excluding those with ACS, according
      to the receiver operating curve analysis FVP = 11.5 mmHg predicted IAH with a
      sensitivity and specificity of 84.8 and 67.0% (AUC of 0.83 (95% CI 0.81-0.86)
      with P < 0.001). FVP = 14.5 mmHg predicted IAP above 20 mmHg with a sensitivity
      of 91.3% and specificity of 68.1% (AUC 0.85 (95% CI 0.79-0.91), P < 0.001).
      Finally, at study entry, the mean IAP in patients with a BMI less then 30 kg/m(2)
      was 10.6 +/- 4.0 mmHg versus 13.8 +/- 3.8 mmHg in patients with a BMI >= 30
      kg/m(2) (P < 0.001). CONCLUSIONS: FVP cannot be used as a surrogate measure of
      IAP unless IAP is above 20 mmHg.

PMID- 21739342
TI  - Unexpected awakening from comatose thyroid storm after a single intravenous
      injection of L-carnitine.

PMID- 21739343
TI  - 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and
      risk of death.
AB  - 2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but
      unfortunately is associated with an unacceptably high rate of significant adverse
      effects. DNP is sold mostly over the internet under a number of different names
      as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation;
      the classic symptom complex associated with toxicity of phenol-based products
      such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and
      tachypnoea, eventually leading to death. Fatalities related to exposure to DNP
      have been reported since the turn of the twentieth century. To date, there have
      been 62 published deaths in the medical literature attributed to DNP. In this
      review, we will describe the pattern and pathophysiology of DNP toxicity and
      summarise the previous fatalities associated with exposure to DNP.

PMID- 21739344
TI  - The use of recreation planning tools in U.S. Forest Service NEPA assessments.
AB  - U.S. Forest Service managers are required to incorporate social and biophysical
      science information in planning and environmental analysis. The use of science is
      mandated by the National Environmental Policy Act, the National Forest Management
      Act, and U.S. Forest Service planning rules. Despite the agency's emphasis on
      'science-based' decision-making, little is known about how science is actually
      used in recreation planning and management. This study investigated the
      perceptions of Forest Service interdisciplinary (ID) team leaders for 106 NEPA
      projects dealing with recreation and travel management between 2005 and 2008. Our
      survey data show how managers rate the importance of social and biophysical
      science compared to other potential 'success factors' in NEPA assessments. We
      also explore how team leaders value and use multi-disciplinary tools for
      recreation-related assessments. Results suggest that managers employ a variety of
      recreation planning tools in NEPA projects, but there appears to be no common
      understanding or approach for how or when these tools are incorporated. The
      Recreation Opportunity Spectrum (ROS) was the most frequently used planning tool,
      but the Visitor Experience and Resource Protection (VERP) framework was the most
      consistently valued tool by those who used it. We recommend further evaluation of
      the strengths and weaknesses of each planning tool and future development of
      procedures to select appropriate planning tools for use in recreation-related
      NEPA assessments.

PMID- 21739345
TI  - Long-term outcome of transcatheter subsegmental and segmental arterial
      chemoemobolization using lipiodol for hepatocellular carcinoma.
AB  - PURPOSE: To clarify the efficacy of transcatheter hepatic sub-subsegmental,
      subsegmental, and segmental arterial chemoembolization using lipiodol (subseg/seg
      lip-TACE) for hepatocellular carcinoma (HCC), long-term outcomes of patients who
      had been treated using subseg/seg lip-TACE alone were retrospectively examined.
      MATERIALS AND METHODS: Subjects comprised 199 patients with HCC
      (T1/2/>=3=30/108/61; Child-Pugh A/B/C=115/52/32; Japan Integrated Staging [JIS]
      score<=1/2/>=3=88/64/47) who underwent subseg/seg lip-TACE using lipiodol mixed
      with an anticancer drug followed by injection of gelatin sponge particles. Each
      patient was followed-up every 3 months, and repeat subseg/seg lip-TACE and/or
      conventional lip-TACE was performed in cases showing recurrence. One-, 3-, 5-, 7
      , and 10-year cumulative survival rates were calculated. Subgroup analyses were
      performed by stratifying the population according to T-factor, Child-Pugh
      classification, and JIS score. RESULTS: Median duration of follow-up was 3.8
      years (range 0.2 to 16.4). Median overall survival was 3.8 years. One-, 3-, 5-, 7
      and 10-year survival rates were 91.5, 66.1, 38.8, 20.3, and 9.4% for all
      patients, and 95.5, 76.9, 51.9, 27.9 and 20.4% for patients with JIS<=1,
      respectively. Significant survival differences were found across two subgroups of
      staging systems (T2 vs. T3<=[P=0.0012] and JIS score<=1 vs. 2 [P=0.0036]).
      CONCLUSION: This study demonstrated that subseg/seg lip-TACE is a feasible
      treatment for obtaining prolonged survival in patients with localized HCC showing
      rich vasculature. Outcomes are influenced by both tumor stage and liver function,
      as seen in the best prolonged survival in patients with JIS score<=1.

PMID- 21739346
TI  - Safety in medical simulation--overlooked or underappreciated?

PMID- 21739347
TI  - Wld(S) protects against peripheral neuropathy and retinopathy in an experimental
      model of diabetes in mice.
AB  - AIMS/HYPOTHESIS: We aimed to evaluate the effect of the mutant Wld(S) (slow
      Wallerian degeneration; also known as Wld) gene in experimental diabetes on early
      experimental peripheral diabetic neuropathy and diabetic retinopathy. METHODS:
      The experiments were performed in four groups of mice: wild-type (WT),
      streptozotocin (STZ)-induced diabetic WT, C57BL/Wld(S) and STZ-induced diabetic
      C57BL/Wld(S). In each group, intraperitoneal glucose and insulin tolerance tests
      were performed; blood glucose, glycated haemoglobin and serum insulin were
      monitored. These mice were also subjected to the following behavioural tests:
      grasping test, hot-plate test and von Frey aesthesiometer test. For some animals,
      sciatic-tibial motor nerve conduction velocity, tail sensory nerve conduction
      velocity and eye pattern electroretinogram were measured. At the end of the
      experiments, islets were isolated to detect glucose-stimulated insulin secretion,
      ATP content and extent of apoptosis. The NAD/NADH ratio in islets and retinas was
      evaluated. Surviving retinal ganglion cells were estimated by
      immunohistochemistry. RESULTS: We found that the Wld(S) gene is expressed in
      islets and protects beta cells against multiple low doses of STZ by increasing
      the NAD/NADH ratio, maintaining the ATP concentration, and reducing apoptosis.
      Consistently, significantly higher insulin concentrations, lower blood glucose
      concentrations, and better glucose tolerance were observed in Wld(S) mice
      compared with WT mice after STZ treatment. Furthermore, Wld(S) alleviated
      abnormal sensory responses, nerve conduction, retina dysfunction and reduction of
      surviving retinal ganglion cells in STZ-induced diabetic models.
      CONCLUSIONS/INTERPRETATION: We provide the first evidence that expression of the
      Wld(S) gene decreases beta cell destruction and preserves islet function in STZ
      induced diabetes, thus revealing a novel protective strategy for diabetic models.

PMID- 21739348
TI  - Fecal carriage of serotype K1 Klebsiella pneumoniae ST23 strains closely related
      to liver abscess isolates in Koreans living in Korea.
AB  - We determined the fecal carriage rate of serotype K1 Klebsiella pneumoniae in
      healthy Koreans and studied their genetic relationship with liver abscess
      isolates. We compared the carriage according to the country of residence. The
      stool specimens were collected through health promotion programs in Korea. K.
      pneumoniae strains were selected and tested for K1 by PCR. Serotype K1 isolates
      were characterized by multilocus sequence typing and pulsed field gel
      electrophoresis. A total of 248 K. pneumoniae isolates were obtained from 1,174
      Koreans. Serotype K1 was identified in 57 (4.9%), of which 54 (94.7%) were ST 23
      and were closely related to the liver abscess isolates. Participants aged >25
      years showed a higher fecal carriage rate than those <= 25 (P = 0.007). The
      proportion of serotype K1 out of K. pneumoniae isolates in foreigners of Korean
      ethnicity who had lived in other countries was lower compared with those who had
      lived in Korea (5.6% vs 24.1%, P = 0.024). A substantial proportion of Koreans
      >25 years carries serotype K1 K. pneumoniae ST23 strains, which are closely
      related to liver abscess isolates. Differences in carriage rates by country of
      residence suggests that environmental factors might play an important role in the
      carriage of this strain.

PMID- 21739349
TI  - Comparison of fluoroscopy-guided Pull-type percutaneous radiological gastrostomy
      (Pull-type-PRG) with conventional percutaneous radiological gastrostomy (Push
      type-PRG): clinical results in 253 patients.
AB  - OBJECTIVES: To analyze the clinical results and complications of fluoroscopy
      guided internal-external Pull-type percutaneous radiological gastrostomy (Pull
      type-PRG) and conventional external-internal percutaneous radiological
      gastrostomy (Push-type-PRG). METHODS: A total of 253 patients underwent
      radiological gastrostomy between January 2002 and January 2010. Data were
      collected retrospectively from radiology reports, Chart review of clinical notes,
      procedure reports, discharge summaries and subsequent hospital visits.
      Statistical analysis was performed to compare the two methods for gastrostomy
      with respect to peri-interventional aspects and clinical results. RESULTS: 128
      patients received the Pull-type-PRG whereas the other 125 patients were served
      with the Push-type-PRG. Indications for gastrostomy were similar in these two
      groups. The most frequent indications for the both methods were stenotic
      oesophageal tumors or head/neck tumors (54.7% in Pull-type-PRG, 68% in Push-type
      PRG). Gastrostomy procedures were successful in 98.3% in Pull-type-PRG compared
      to 92% in Push-type-PRG. There was no procedure-related mortality. Compared to
      Push-type-PRG, the peri-interventional complication rate was significantly
      reduced in Pull-type-PRG (14.8% versus 34.4%, P = 0.002). CONCLUSIONS: Compared
      to the external-internal Push-type-PRG, the internal-external Pull-type-PRG
      showed a high primary success rate and a decreased incidence of peri
      interventional complications.

PMID- 21739350
TI  - Comparison of hand-sewn, linear-stapled, and circular-stapled gastrojejunostomy
      in laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: There is no consensus on the ideal gastrojejunostomy anastomosis
      (GJA) technique in laparoscopic Roux-en-Y gastric bypass (LRYGB). We reviewed our
      experience with three GJA techniques (hand-sewn (HSA), linear-stapled (LSA), and
      25-mm circular-stapled (CSA)) to determine which anastomosis technique is
      associated with the lowest early (60-day) anastomotic complication rates.
      METHODS: From November 2004 through December 2009, 882 consecutive patients
      underwent LRYGB using three GJA techniques: HSA, LSA, and CSA. All patients had a
      minimum of 2 months follow-up. Records were reviewed for postoperative
      gastrojejunostomy leak, stricture, and marginal ulcer, and these early
      complications were classified according to anastomosis technique. Multivariate
      analysis was performed to determine associations between complications and
      anastomosis technique. RESULTS: Preoperative demographics, length of hospital
      stay, and postoperative follow-up did not differ between the three groups. The
      majority of patients underwent LSA (n = 514, 61.6%) followed by HSA (n = 180,
      21.6%) and CSA (n = 140, 16.8%). Using multivariate analysis, there were no
      statistically significant differences in the rates of leak (LSA 1.0%, HSA 1.1%,
      CSA 0.0%, p = 0.480), stricture (LSA 6.0%, HSA 6.1%, CSA 4.3%, p = 0.657), or
      marginal ulcer (LSA 8.0%, HSA 7.7%, CSA 3.6%, p = 0.180). CONCLUSIONS: The three
      techniques can be used safely with a low complication rate. Our data do not
      identify a superior anastomosis technique.

PMID- 21739351
TI  - Sensoric potential of gold-silver core-shell nanoparticles.
AB  - The sensitivities of five different core-shell nanostructures were investigated
      towards changes in the refractive index of the surrounding medium. The shift of
      the localized surface plasmon resonance (LSPR) maximum served as a measure of the
      (respective) sensitivity. Thus, gold-silver core-shell nanoparticles (NPs) were
      prepared with different shell thicknesses in a two-step chemical process without
      the use of any (possibly disturbing) surfactants. The measurements were supported
      by ultramicroscopic images in order to size the resulting core-shell structures.
      When compared to sensitivities of nanostructures reported in the literature with
      those of the (roughly spherical) gold-silver core-shell NPs, the latter showed
      comparable (or even higher) sensitivities than gold nanorods. The experimental
      finding is supported by theoretical calculation of optical properties of such
      core-shell NP. Extinction spectra of ideal spherical and deformed core-shell NPs
      with various core/shell sizes were calculated, and the presence of an optimal
      silver shell thickness with increased sensitivity was confirmed. This effect is
      explained by the existence of two overlapping plasmon bands in the NP, which
      change their relative intensity upon change of refractive index. Results of this
      research show a possibility of improving LSPR sensor by adding an extra metallic
      layer of certain thickness.

PMID- 21739352
TI  - Identification of C4 photosynthesis metabolism and regulatory-associated genes in
      Eleocharis vivipara by SSH.
AB  - This is the first effort to investigate the candidate genes involved in kranz
      developmental regulation and C(4) metabolic fluxes in Eleocharis vivipara, which
      is a leafless freshwater amphibious plant and possesses a distinct culms anatomy
      structure and photosynthetic pattern in contrasting environments. A terrestrial
      specific SSH library was constructed to investigate the genes involved in kranz
      anatomy developmental regulation and C(4) metabolic fluxes. A total of 73 ESTs
      and 56 unigenes in 384 clones were identified by array hybridization and
      sequencing. In total, 50 unigenes had homologous genes in the databases of rice
      and Arabidopsis. The real-time quantitative PCR results showed that most of the
      genes were accumulated in terrestrial culms and ABA-induced culms. The C(4)
      marker genes were stably accumulated during the culms development process in
      terrestrial culms. With respect to C(3) culms, C(4) photosynthesis metabolism
      consumed much more transporters and translocators related to ion metabolism,
      organic acids and carbohydrate metabolism, phosphate metabolism, amino acids
      metabolism, and lipids metabolism. Additionally, ten regulatory genes including
      five transcription factors, four receptor-like proteins, and one BURP protein
      were identified. These regulatory genes, which co-accumulated with the culms
      developmental stages, may play important roles in culms structure developmental
      regulation, bundle sheath chloroplast maturation, and environmental response.
      These results shed new light on the C(4) metabolic fluxes, environmental
      response, and anatomy structure developmental regulation in E. vivipara.

PMID- 21739353
TI  - Intercellular production of tamavidin 1, a biotin-binding protein from Tamogitake
      mushroom, confers resistance to the blast fungus Magnaporthe oryzae in transgenic
      rice.
AB  - The blast fungus Magnaporthe oryzae, one of the most devastating rice pathogens
      in the world, shows biotin-dependent growth. We have developed a strategy for
      creating disease resistance to M. oryzae whereby intercellular production of
      tamavidin 1, a biotin-binding protein from Pleurotus cornucopiae occurs in
      transgenic rice plants. The gene that encodes tamavidin 1, fused to the sequence
      for a secretion signal peptide derived from rice chitinase gene, was connected to
      the Cauliflower mosaic virus 35S promoter, and the resultant construct was
      introduced into rice. The tamavidin 1 was accumulated at levels of 0.1-0.2% of
      total soluble leaf proteins in the transgenic rice and it was localized in the
      intercellular space of rice leaves. The tamavidin 1 purified from the transgenic
      rice was active, it bound to biotin and inhibited in vitro growth of M. oryzae by
      causing biotin deficiency. The transgenic rice plants showed a significant
      resistance to M. oryzae. This study shows the possibility of a new strategy to
      engineer disease resistance in higher plants by taking advantage of a pathogen's
      auxotrophy.

PMID- 21739354
TI  - Spectral unmixing imaging of wavelength-responsive fluorescent probes: an
      application for the real-time report of amyloid Beta species in Alzheimer's
      disease.
AB  - PURPOSE: The goal of the study was to investigate a method for the real-time
      assessment of a target concentration in vivo using a combination of a spectral
      unmixing technique and a fluorescent probe specific for amyloid beta (Abeta)
      species, the biomarkers for Alzheimer's disease (AD). PROCEDURES: The probe
      CRANAD-3 has a significant emission wavelength shift upon binding to Abeta
      species. It was used to differentiate a bound probe from an unbound probe in a
      phantom, ex vivo in brain slices and whole brain, and in vivo in a transgenic
      mouse model of AD. RESULTS: The ex vivo unmixing imaging of AD brain clearly
      showed differential distribution of the bound and unbound probes between the
      brain tissue and blood vessels. The in vivo unmixed signals of bound CRANAD-3
      reached a plateau with increasing dosage, demonstrating that these signals
      correspond to Abeta content, not probe injected dose. CONCLUSION: This study
      provided evidence that signals processed by the spectral unmixing technique could
      be used as a real-time reporter of Abeta species loading in vivo and ex vivo.

PMID- 21739356
TI  - [Traumatic injuries of the sternoclavicular joint].
AB  - Traumatic injuries of the sternoclavicular joint occur rarely and are mainly
      caused by an indirect trauma mechanism with high kinetic energy. Anterior
      dislocation is much more common than posterior dislocation, which may be
      associated with life-threatening injuries. The CT scan is the diagnostic tool of
      choice for accurate assessment of the injury and coexisting pathologies. The
      primary goal in anterior and posterior dislocations is an early closed reduction.
      In cases of redislocation after closed reduction of an anterior dislocation we
      recommend primary joint reconstruction on the basis of an individual therapeutic
      concept. Posterior dislocations often cannot be reduced by closed means. Then
      open reconstruction and stabilization are performed. Chronic instabilities should
      only be addressed surgically in cases of persistent pain and/or functional
      deficit. Resection of the medial clavicula represents an effective treatment
      option in post-traumatic sternoclavicular joint arthritis provided that the
      costoclavicular ligaments are intact or will be reconstructed during surgery.
      Physeal injuries of the medial clavicle can occur until an approximate age of 25.
      Closed reduction of dislocated physeal injuries is attempted. After reposition
      non-operative treatment in general leads to a good functional outcome.
      Posteriorly dislocated physeal injuries often cannot be reduced by closed means.
      In these cases good function can be expected after open stabilization.

PMID- 21739357
TI  - [Stabilization of post-traumatic instability of the sternoclavicular joint.
      Treatment of acute and chronic symptomatic joint instability].

PMID- 21739359
TI  - Healthcare-acquired infections in rehabilitation units of the Lombardy Region,
      Italy.
AB  - BACKGROUND: Little data are available on the frequency and risk factors for
      infection in patients in rehabilitation units. METHODS: This was a 2-year
      retrospective cohort study conducted in 131 rehabilitation units (RUs) of the
      Lombardy Region, including those for patients requiring musculoskeletal, cardiac,
      respiratory, neurological and general geriatric rehabilitation. RUs were
      stratified into three groups by infection rate calculated from administrative
      data, and a random sample of RUs in each group was selected for analysis.
      Discharges from these RUs were randomly selected for chart review, and healthcare
      acquired infection was confirmed using CDC/NHSN definitions. A logistic
      regression analysis explored the association among demographic variables of age,
      sex, type of rehabilitation unit, Charlson comorbidity score, and location prior
      to RU admission for selected infections. RESULTS: For the 3,028 discharges from
      28 RUs, hospital administrative data had a sensitivity of 0.45 and a positive
      predictive value of 0.89 to identify infections in the chart review. At least one
      infection occurred in 14.9% of patient discharges, with 71% of infections being
      urinary, 8.0% respiratory, and 5% skin and soft tissue. Urinary infection was
      associated with female sex [odds ratio (OR) 1.48, 95% confidence interval (CI)
      1.13-1.93], age 75-85 years (OR 2.21, 95% CI 1.12-4.34), Charlson comorbidity
      score of >=3 (OR 1.54, 95% CI 1.10-2.17), and the transfer from acute care (OR
      1.45, 95% CI 1.04-2.02). For respiratory infection, male sex (OR 3.06, 95% CI
      1.51-6.18), comorbidity score of 1 or 2 (OR 2.16, 95% CI 1.08-4.36), and transfer
      from a healthcare setting other than an acute care hospital were independent
      risks (OR 3.14, 95% CI 1.15-8.53). CONCLUSION: Infections are common in residents
      of these rehabilitation units, and risk factors may differ with type of
      infection. The proportion of infections which may be prevented and effective
      prevention strategies need to be determined.

PMID- 21739360
TI  - Natural leukocyte interferon alpha (Alfaferone) combined with ribavirin in the
      treatment of patients with HCV-related cirrhosis: our experience.
AB  - BACKGROUND: The aim of the study was to evaluate the efficacy and safety of
      combined treatment with natural leukocyte interferon alpha (Alfaferone) plus
      ribavirin in patients with HCV-related cirrhosis. PATIENTS AND METHODS: Twenty
      three patients (15 women, 8 men) aged 17-68 years hospitalized in 2005-2008 were
      included in the study. Seventeen patients who qualified for treatment were Child
      Pugh class A patients and 6 others were class B. Seventeen patients had genotype
      1b and 6 genotype 3a infection. Thirteen patients were naive, retherapy concerned
      8 patients, and in two cases the continuation of treatment had been stopped
      because of adverse events following the use of pegylated interferons. The
      treatment was continued for 48 weeks regardless of HCV genotype. Normalized AlAT
      activity (<40 U/l) was the measure of biochemical efficacy of the treatment,
      while virological efficacy was reflected by an undetectable viral load in plasma.
      Both measurements were conducted immediately after the end of treatment (EOT) and
      after a 6-month follow-up period (SVR). Therapeutic safety was evaluated by the
      monitoring of the adverse events of the treatment. RESULTS: Abnormal AlAT levels
      prior to treatment were detected in 20/23 patients. During therapy normalized
      levels were achieved in 50% of them, and after 6 months they were sustained in
      9/20. EOT was achieved in 6/19 patients and SVR in 3 patients. Mild psychiatric
      disorders were the most frequently detected adverse events (12 patients).
      Thrombocytopenia and leucopenia existing prior to treatment did not intensify
      during the treatment. Severe adverse events caused by the drug resulted in the
      discontinuation of treatment in three patients (urinary tract infections,
      depression, myasthenia gravis), of whom two patients were Child-Pugh class A and
      one was class B. In one patient treatment was discontinued because of HCC.
      CONCLUSION: Natural leukocyte interferon alpha is well tolerated by patients with
      HCV-related cirrhosis and coexisting thrombocytopenia and leucopenia.

PMID- 21739361
TI  - Penetration of lysozyme and cytochrome C in lipid bilayer: fluorescent study.
AB  - Lysozyme and cytochrome c (CytC) are well-investigated proteins. Their specific
      interactions with lipid membranes, however, keep surprising secrets. Lysozyme
      destroys bacterial membrane; CytC binds hydrophobically to alkyl chains of the
      membrane lipid tails, indicating that both proteins are able to interact directly
      with the inner membrane components, especially with the fatty acyl chains of
      membrane lipids. The degrees of integration, depth of localization in the
      hydrophobic interior of different types of model membranes, and the type of
      interaction of lysozyme and CytC with surrounding lipids were investigated by
      fluorescent spectroscopy. Three different fluorescent markers, located at
      approximately 6.5, 9, and 18 A into the lipid bilayer, were used. In addition,
      liposomes were designed as electrically neutral or positively or negatively
      charged to unravel the importance of the net electrical charge for lipid/protein
      interaction. CytC penetrates deeper into the lipid bilayer in comparison with
      lysozyme, and data are discussed in the terms of Stern-Volmer quenching of
      fluorescence.

PMID- 21739362
TI  - Electrostatic oscillations along cylindrical micelles.
AB  - Theoretical analysis of ionic electrostatic oscillations of a charged cylindrical
      micelle is presented within the framework of the fluid theory for surface
      counterions of the cell, in conjunction with the Poisson equation. General
      expression of dispersion relation is obtained for electrostatic excitations of
      system.

PMID- 21739363
TI  - Orexin a in cortical cultures: expression and effect on synaptogenesis during
      development.
AB  - Orexin A (OXA) is an excitatory hypothalamic neurotransmitter and ligand for
      Orexin Receptor-1 (OR1), isolated from a small group of hypothalamic neurons. OXA
      orchestrates different brain functions, and at the cognitive level some of the
      effects of insufficiency of OXA are well-known, for example in Parkinson's
      disease. It is widely assumed that deteriorated cognitive processes are related
      to impaired network connectivity. However, little is known about the effects of
      OXA in network connectivity and synaptogenesis. Therefore, to obtain insight into
      this problem we designed experiments with two groups of networks of dissociated
      cortical neurons: one group incubated in a plain medium and another chronically
      treated with OXA. After 1, 2, 3 or 4 weeks in vitro we applied
      immunocytochemistry for detection of OXA, OR1, and synaptic marker synaptophysin.
      Shortly after plating, 91 +/- 8% of the neurons cultivated in a plain medium
      expressed OXA-immunoreactivity, which does normally not occur in vivo indicating
      that neurons may change their phenotype under non-natural culture conditions to
      develop synaptically coupled networks. The fraction of orexinergic neurons
      decreased to 33 +/- 21% after 4 weeks in vitro. OXA expression was highest in the
      first week of network formation, the period of maximum synaptogenesis, and then
      decreased and stabilized in the weeks thereafter. Our hypothesis that OXA plays a
      role in the network development as a synaptogenic factor was supported by higher
      levels, earlier onset, and sustained increase of synaptophysin expression in
      experiments with chronic OXA application to the culture medium.

PMID- 21739364
TI  - Unique induction of CA1 LTP components after intake of theanine, an amino acid in
      tea leaves and its effect on stress response.
AB  - Theanine, gamma-glutamylethylamide, is one of the major amino acid components in
      green tea. This study was undertaken to evaluate the effect of theanine intake on
      long-term potentiation (LTP) induction at hippocampal CA1 synapses and exposure
      to acute stress. Young rats were fed water containing 0.3% theanine after birth.
      KEY FINDINGS: Serum corticosterone level was markedly decreased by theanine
      intake. Because this decrease can modify synaptic plasticity, the effect of
      theanine intake was examined focused on CA1 LTP induction. CA1 LTP induced by a
      100-Hz tetanus for 1 s was almost the same extent in hippocampal slices from
      theanine-administered rats, whereas that induced by a 200-Hz tetanus for 1 s was
      significantly attenuated. 2-Amino-5-phosphonovalerate (APV), an N-methyl-D: 
      aspartate (NMDA) receptor antagonist, significantly attenuated CA1 LTP induced by
      a 200-Hz tetanus in the control rats, but not in theanine-administered rats.
      Interestingly, APV completely blocked CA1 LTP induced by a 100-Hz tetanus in the
      control rats, while scarcely blocking it in theanine-administered rats. These
      results indicate that theanine intake reduces NMDA receptor-dependent CA1 LTP,
      while increasing NMDA receptor-independent CA1 LTP. Furthermore, neither 100-Hz
      tetanus-induced LTP nor 200-Hz tetanus-induced LTP was attenuated in theanine
      administered rats after exposure to tail suspension stress, suggesting that the
      lack of NMDA receptor-dependent CA1 LTP by theanine intake is involved in
      ameliorating the attenuation of CA1 LTP after tail suspension. This study is the
      first to indicate that theanine intake modifies the mechanism of CA1 LTP
      induction.

PMID- 21739366
TI  - [Headache].

PMID- 21739365
TI  - Role of various proteases in cardiac remodeling and progression of heart failure.
AB  - It is believed that cardiac remodeling due to geometric and structural changes is
      a major mechanism for the progression of heart failure in different pathologies
      including hypertension, hypertrophic cardiomyopathy, dilated cardiomyopathy,
      diabetic cardiomyopathy, and myocardial infarction. Increases in the activities
      of proteolytic enzymes such as matrix metalloproteinases, calpains, cathepsins,
      and caspases contribute to the process of cardiac remodeling. In addition to
      modifying the extracellular matrix, both matrix metalloproteinases and cathepsins
      have been shown to affect the activities of subcellular organelles in
      cardiomyocytes. The activation of calpains and caspases has been identified to
      induce subcellular remodeling in failing hearts. Proteolytic activities
      associated with different proteins including caspases, calpain, and the ubiquitin
      proteasome system have been shown to be involved in cardiomyocyte apoptosis,
      which is an integral part of cardiac remodeling. This article discusses and
      compares how the activities of various proteases are involved in different
      cardiac abnormalities with respect to alterations in apoptotic pathways, cardiac
      remodeling, and cardiac dysfunction. An imbalance appears to occur between the
      activities of some proteases and their endogenous inhibitors in various types of
      hypertrophied and failing hearts, and this is likely to further accentuate
      subcellular remodeling and cardiac dysfunction. The importance of inhibiting the
      activities of both extracellular and intracellular proteases specific to distinct
      etiologies, in attenuating cardiac remodeling and apoptosis as well as
      biochemical changes of subcellular organelles, in heart failure has been
      emphasized. It is suggested that combination therapy to inhibit different
      proteases may prove useful for the treatment of heart failure.

PMID- 21739367
TI  - [Neuropathic and tumour-induced headache: Therapeutic options].
AB  - Cancer pain in the field of otolaryngology can be effectively alleviated. Only
      very few questions regarding the patient's history of pain are required to
      understand the type of pain being dealt with and to be able to make the correct
      selection of analgetic agents. It is particularly important to treat tumor
      breakthrough pain appropriately, for which a sufficient number of therapeutic
      agents are available. The present article comments on the various possibilities
      of specific drugs and interventional therapeutic approaches, as well as their
      specific characteristics within the field of otolaryngology, supplemented with
      various tricks for their practical application. Using these basic rules, most
      problems can be identified and specific treatments optimized. The progression of
      cancer pain may show wide dynamic ranges, and the therapeutic approach should
      always be adjusted to the current situation. Palliative care of a cancer patient
      may be particularly challenging in that, not only the treatment of pain, but also
      the treatment of respiratory distress is of key importance.

PMID- 21739368
TI  - [The quality of diagnostic classification using abridged versions of the tinnitus
      questionnaire: comparative analysis].
AB  - BACKGROUND: There are different abridged versions of the tinnitus questionnaire
      (TQ) and reference values for grading tinnitus-related distress, the diagnostic
      value of which is unclear, as is the relation of sensitivity to specificity, as
      well as positive and negative predictive values. The present study is aimed at
      clarifying these issues and at benchmarking the existing abridged TQ versions.
      PATIENTS AND METHODS: TQ data from 209 outpatients who had tinnitus for a period
      of at least 4 months were collected at the beginning of treatment. The rate of
      correct severity ratings, the quality of making a distinction between (extremely)
      severe and compensated/moderate tinnitus (area-under curve under the receiver
      operating-characteristics curve, and rate of correct classifications), as well as
      positive and negative predictive values were calculated. RESULTS: Applying
      unspecific reference values (independent of inpatient/outpatient status), the
      most favourable evaluation was achieved by the shortest TQ version (10 items).
      With the 12-item version (mini-TQ), better classification was achieved when
      reference values specific for outpatients were applied instead of unspecific
      values.

PMID- 21739369
TI  - [Radiological diagnosis of the paranasal sinuses].
AB  - Although diseases of the paranasal sinuses have a relatively homogeneous clinical
      presentation, their causes can vary considerably. Radiological imaging only
      became relevant in paranasal sinus diagnostics following the introduction of
      cross-sectional imaging. In addition to technical details on imaging procedures
      and the individual criteria of the different modalities, anatomic details and
      congenital variations are presented. Particularly in acute inflammatory diseases
      as well as traumatic lesions, imaging is essential in preoperative planning and
      postoperative control. The article gives a detailed description of options in
      radiologic imaging of the paranasal sinuses.

PMID- 21739370
TI  - Efficacy of emodepside plus toltrazuril (Procox((r)) oral suspension for dogs)
      against Toxocara canis, Uncinaria stenocephala and Ancylostoma caninum in dogs.
AB  - The efficacy of emodepside plus toltrazuril (Procox(r) oral suspension for dogs)
      against different species of gastrointestinal nematodes (Toxocara canis,
      Ancylostoma caninum, Uncinaria stenocephala) was evaluated in nine
      randomised,blinded and placebo-controlled laboratory studies in naturally or
      experimentally infected dogs. The product was used at the proposed minimum dose
      of 0.45 mg emodepside and 9 mg toltrazuril per kg body weight. Efficacy was
      calculated based on worm counts after necropsy. Worm burdens in the control dogs
      ranged between 0 and 409 worms of the respective stage for T. canis and between 4
      and 655 worms for hookworms. The studies demonstrated 100 % efficacy of
      emodepside/toltrazuril suspension against mature adult, >= 94.7 %efficacy against
      immature adult and 99.3 % efficacy against the L4 larval stage of T. canis. The
      efficacy against mature adult A. caninum was >= 99.5 % and the efficacy against
      mature adult U. stenocephala was 100 %. All differences between treatment and
      control groups were statistically significant and no gender effect was found. It
      can be concluded that the emodepside/toltrazuril suspension represents a safe and
      highly effective product in dogs with nematode (T. canis, hookworms) infection.

PMID- 21739371
TI  - Efficacy of emodepside plus toltrazuril suspension (Procox((r)) oral suspension
      for dogs) against prepatent and patent infection with Isospora canis and Isospora
      ohioensis-complex in dogs.
AB  - Three randomised, blinded and placebo-controlled laboratory studies were
      conducted to evaluate the efficacy of emodepside plus toltrazuril suspension
      (Procox((r)) suspension for dogs) against Isospora canis and Isospora ohioensis
      complex. Unweaned puppies were experimentally infected with sporulated oocysts of
      I. canis and/or I. ohioensis-complex. In each study, one group was treated during
      prepatency (2 or 4 days post infection) while dogs in the second group were
      treated individually after the onset of oocyst excretion of the respective
      coccidia species. The dogs were treated with the minimum therapeutic dose of 0.45
      mg emodepside and 9 mg toltrazuril per kg body weight. Daily faecal oocyst counts
      from both groups were compared to placebotreated control groups to determine
      efficacy.Dogs treated during prepatent I. canis or I. ohioensis-complex infection
      showed significantly lower oocyst counts for up to 12 days compared to the
      control group. Oocyst counts were reduced by 90.2 - 100 % while the control
      groups continued to exhibit an adequate infection, except for one study where
      efficacy against prepatent I. canis infection faded 13 days after treatment.
      Following treatment of patent I. canis or I. ohioensis-complex infections,
      significantly lowered oocyst counts were observed for up to 9 days compared to
      the control group. Faecal oocyst counts were reduced by 91.5 - 100 %. In all
      three studies the number of days with diarrhoea was significantly lower when dogs
      were treated during prepatent Isospora spp. infection compared to the control
      groups. No adverse drug reactions were observed during the studies. In
      conclusion, the studies demonstrated that emodepside plus toltrazuril suspension
      is an efficient coccidiocide for dogs.

PMID- 21739372
TI  - Field evaluations of the efficacy and safety of Emodepside plus toltrazuril
      (Procox(r) oral suspension for dogs) against naturally acquired nematode and
      Isospora spp. infections in dogs.
AB  - Three controlled, blinded and randomised multicentre field studies evaluated the
      efficacy and safety of a new formulation containing emodepside plus toltrazuril
      (Procox(r) suspension for dogs) against naturally acquired parasite infections in
      dogs. In two studies dogs positive for gastrointestinal nematodes and/or Isospora
      spp. were treated with emodepside/toltrazuril suspension (at least 0.45 mg
      emodepside plus 9 mg toltrazuril per kg body weight) or a reference product
      containing either milbemycin oxime plus praziquantel (Milbemax(r)) or
      sulfadimethoxine (Kokzidiol SD(r)) at recommended dose rates. The third study
      investigated efficacy against prepatent natural Isospora spp. infections in
      comparison to an untreated control group by enrolling Isospora- negative dogs
      that were at risk to develop a patent infection during the study.No suspected
      adverse drug reactions were observed in any of the 403 dogs enrolled in the three
      studies including 234 dogs treated with emodepside/toltrazuril suspension. In
      dogs treated with emodepside/toltrazuril suspension against nematode infection
      faecal egg counts were reduced by 100 % (reference product: 99.7 %). Similarly,
      in the dogs that had been treated against patent Isospora spp. infection, faecal
      oocyst counts were reduced by 100 % (reference product: 99.0 %). In both studies,
      statistical analysis demonstrated non-inferiority and even superiority to the
      reference products (p <= 0.009). Dogs treated with emodepside/toltrazuril
      suspension during suspected prepatent Isospora spp. infection had 98.7 % lower
      faecal oocyst counts after treatment compared to untreated dogs (p < 0.0001).The
      studies demonstrated that emodepside/toltrazuril suspension is safe and highly
      efficacious against nematodes and Isospora spp. under field conditions.

PMID- 21739373
TI  - Efficacy of emodepside/toltrazuril suspension (Procox(r) oral suspension for
      dogs) against mixed experimental Isospora felis/Isospora rivolta infection in
      cats.
AB  - The coccidia Isospora felis and Isospora rivolta are intestinal parasites
      occurring worldwide in domestic cats. In young cats, they can be detected with
      higher prevalence.The effects of toltrazuril in the new combination product
      Procox((r)) oral suspension for dogs containing 0.1 % emodepside and 2 %
      toltrazuril (0.9 mg emodepside + 18 mg toltrazuril per ml) were studied in
      eighteen kittens experimentally infected each with a total of 1 x 10(5) oocysts
      of a mixture of Isospora felis and Isospora rivolta. In the infectious material,
      the quantitative relation of I. felis and I. rivolta was about 1:5. Following a
      three-days period after infection, two groups of 6 kittens were treated during
      the prepatent period with either a single dose of 0.45 mg emodepside + 9 mg
      toltrazuril/kg body weight or 0.9 mg emodepside + 18 mg toltrazuril/kg body
      weight. A group of six kittens without any treatment served as a control. On day
      5 post infection, the untreated kittens started the excretion of oocysts.
      Treatment with both toltrazuril doses significantly reduced oocyst excretion.
      Following the single higher dose, the reduction of oocysts of both Isospora spp.
      was more pronounced (96.7 % to 100 %) in comparison to the lower dose (57.2 % to
      100 %). The Procox((r)) application was well tolerated and no adverse events were
      seen with any of the applied dosages.When administered to kittens and as a single
      treatment during the prepatent period, Procox((r)) is suitable to control the
      number of oocysts excreted in the faeces in case of an Isospora felis and
      Isospora rivolta infection.

PMID- 21739374
TI  - Efficacy of Procox(r) oral suspension for dogs (0.1% emodepside and 2%
      toltrazuril) against experimental nematode (Toxocara cati and Ancylostoma
      tubaeforme) infections in cats.
AB  - Two exploratory studies were performed to determine the optimum therapeutic dose
      of Procox((r)) for the removal of experimental infection with mature adult
      Toxocara (T.) cati and Ancylostoma (A.) tubaeforme in kittens. Procox((r)) is a
      new oral suspension containing a combination of the nematocidal and coccidiocidal
      active principles emodepside (0.1 %) and toltrazuril (2 %).In the first study, 18
      eight-weeks-old kittens were inoculated with 450 L3 larvae of T. cati. 56 days
      after infection, the kittens were allocated to three treatment groups and were
      treated with 0.5 mg emodepside/kg body weight (group 1), 0.25 mg emodepside/kg
      body weight (group 2) and 0.1 mg emodepside/kg body weight (group 3),
      respectively. In the second study, 10 eight-weeks-old kittens were inoculated
      with 350 L3 larvae of A. tubaeforme. Four weeks after infection, the kittens were
      allocated to two treatment groups and were treated with 0.1 mg emodepside/kg body
      weight (group 1) or 0.25 mg emodepside/kg body weight (group 2). In both studies,
      all kittens received a reference treatment with Drontal((r)) (230 mg pyrantel
      embonate and 20 mg praziquantel per tablet) at the recommended dose of one
      tablet/4 kg body weight 5 days after treatment with Procox((r)). Anthelmintic
      efficacy was calculated by reduction in worm numbers expelled with the faeces
      following treatment with Procox((r)) as compared with faecal worm numbers after
      reference treatment with Drontal((r)), by thus avoiding necropsy of the
      animals.In the T. cati study, emodepside was at 99.9 %, 100 % and 96.5 %
      effective at a dosage of 0.5 mg, 0.25 mg and 0.1 mg per kg body weight,
      respectively. Against A. tubaeforme emodepside was at 95.7 % and 100 % effective
      at a dosage of 0.1 mg and 0.25 mg per kg body weight. No adverse events were seen
      during either study.It can be concluded that Procox((r)) is efficacious for the
      control of mature adult T. cati and A. tubaeforme infections in cats at a single
      dose rate of 0.25 mg emodepside/kg body weight.

PMID- 21739375
TI  - Results of parasitological examinations of faecal samples from cats and dogs in
      Germany between 2003 and 2010.
AB  - In a retrospective study, the results of parasitological examinations of faecal
      samples from 8,560 cats and 24,677 dogs between January 2003 and December 2010 in
      Germany were analysed. 30.4 % of the examined dogs and 22.8 % of the cats were
      infected with endoparasites. The examination of the faecal samples from dogs
      revealed stages of Giardia spp. (18.6 %), Toxocara canis (6.1 %), Toxascaris
      leonina (0.6 %), Ancylostomatidae (2.2 %), Trichuris vulpis (1.2 %), Capillaria
      spp. (1.3 %), Crenosoma vulpis (0.4 %), Angiostrongylus vasorum (0.5 %),
      Taeniidae (0.4 %), Dipylidiidae (< 0.1 %), Mesocestoides spp. (< 0.1 %), Isospora
      spp. (5.6 %), I. ohioensis-complex (3.9 %), I. canis (2.4 %), Sarcocystis spp.
      (2.2 %) and Hammondia heydorni/Neospora caninum (0.3 %). Dogs in the age groups
      up to 3 months and > 3 up to 6 months of age showed significantly higher
      infection rates with Giardia spp. (37.5 % and 38.2 %, respectively), Toxocara
      canis (12.0 % and 12.4 %, respectively), Toxascaris leonina (1.1 % and 1.6 %,
      respectively), Isospora spp. (23.4 % and 11.8 %, respectively), I. ohioensis
      complex (15.6 % and 7.2 %, respectively) and I. canis (11.8 % and 5.2 %,
      respectively) compared to older dogs. In faecal samples from cats, stages of
      Giardia spp. (12.6 %), Toxocara cati (4.7 %), Toxascaris leonina (0.1 %),
      Ancylostoma tubaeforme (0.2 %), Aelurostrongylus abstrusus (0.5 %), Capillaria
      spp. (1.0 %), Taeniidae (0.6 %), Dipylidium caninum (< 0.1 %) Mesocestoides spp.
      (< 0.1 %), Isospora spp. (6.0 %), I. felis (4.4 %), I. rivolta (2.2 %),
      Toxoplasma gondii/Hammondia hammondi (0.8 %) and Sarcocystis spp. (0.3 %) were
      detected. Cats in the age groups up to 3 months and > 3 up to 6 months of age
      showed significantly higher infection rates with Giardia spp. (19.5 % and 24.0 %,
      respectively), T. cati (8.1 % and 6.9 %, respectively), Isospora spp. (12.8 % and
      8.6 %, respectively), I. felis (10.0 % and 5.9%, respectively) and I. rivolta
      (4.6 % and 2.9%, respectively) compared to older cats.

PMID- 21739376
TI  - Diagnosis of imported canine filarial infections in Germany 2008 - 2010.
AB  - Filarial infections of dogs are attracting attention across Europe because of the
      risk of spread into previously non-endemic areas (e.g. Dirofilaria repens with
      Culicidae as vectors) and as emerging zoonotic agents. The occurrence of filarial
      infections in German dogs has been analysed based on 8,545 samples collected
      either from imported animals or following travel into endemic regions. All
      samples were tested by means of modified Knott's test and heartworm antigen assay
      within the period 2008 - 2010. Heartworm antigen was detected in 127 samples
      (1.49 %; 95 % CI: 1.25 - 1.77 %), but only 38 dogs also had microfilariae in
      their blood samples. On the other hand, 125 animals (1.46 %; 95 % CI: 1.23 - 1.74
      %) were only positive in the Knott's test. For discrimination by means of PCR and
      sequencing a total of 73 blood samples as well as two samples of adult worms were
      included, which have been sent by veterinarians during 2008 - 2010. A mono
      infection caused by D. repens was detected in 35 cases, while D. immitis was
      proven in 15 samples, with 6 of these showing a combination of D. immitis and D.
      repens. Imported Dipetalonema dracunculoides (transmitted by Rhipicephalus
      sanguineus or Hippobosca longipennis) or Acanthocheilonema reconditum (fleas and
      lice serve as intermediate hosts) infections were diagnosed in 24 cases and in a
      single sample a co-infection of A. reconditum and D. repens was evident. D.
      repens was the most common filarial infection imported and it was introduced into
      Germany from eleven European countries. Slovenia and Hungary are reported for the
      first time as endemic for D. repens and A. reconditum, respectively. Furthermore
      this study reports, to the best of our knowledge, for the first time import of D.
      dracunculoides from the Canary Islands, A. reconditum from Majorca, D. immitis
      from Corfu and a co-infection of D. repens and A. reconditum from Spain as well
      as mixed infections of D. repens and D. immitis from Corfu, Sardinia and
      Bulgaria. Co-infections with other arthropod-borne infections as well as
      therapeutical follow-up were also considered. Selamectin (as spot-on formulation)
      was not able to clear microfilaraemia in dogs infected with either D. repens, A.
      reconditum or D. dracunculoides, whereas a topical moxidectin/imidacloprid
      formulation was able to eliminate microfilariae in one dog infected with A.
      reconditum.

PMID- 21739377
TI  - Evaluation of the therapeutic and preventive efficacy of 2.5 % moxidectin / 10 %
      imidacloprid (Advocate((r)), Bayer animal health) in dogs naturally infected or
      at risk of natural infection by Dirofilaria repens.
AB  - The objective of this GCP-compliant clinical field study was to evaluate the
      efficacy of the combination of moxidectin (minimum dose of 2.5 mg/kg body weight)
      and imidacloprid (minimum dose of 10.0 mg/kg body weight) spot-on (Advocate((r)))
      as a preventive and therapeutic treatment of natural infection by Dirofilaria
      repens in dogs in the Czech Republic.There were two arms of the study, both
      negatively controlled. 34 animals were randomly allocated to two groups of the
      treatment arm; 90 negative animals were randomly allocated to the prevention arm
      groups. All enrolled dogs were observed physically and blood was sampled monthly
      for Dirofilaria repens microfilaria counts for 18 months by modified Knott test
      and PCR. 34 dogs were positive for microfilaria and enrolled in the treatment arm
      of this study (treated: 18, untreated: 16). The reduction of the log-transformed
      microfilaria counts was significantly higher in the treatment group on day 28 (p
      = 0.007), 56, 84 and 112 (p < 0.001). All animals treated were negative after a
      single treatment. In the untreated control group 93.75 % remained positive (p <
      0.001). 87 dogs were negative for microfilaria prior to allocation to the
      "preventive" arm (treated: 49; untreated: 38; 3 excluded). One dog in the
      untreated control group became positive for Dirofliaria repens microfilaria,
      while none of the treated dogs became positive. Advocate((r)) was effective in
      the treatment of dogs infected with microfilaria of Dirofilaria repens. Due to
      the low rate of natural infections the preventive efficacy could not be proven,
      but no dog treated became positive.

PMID- 21739378
TI  - Canine and feline infections by cardiopulmonary nematodes in central and southern
      Italy.
AB  - Capillaria aerophila, Aelurostrongylus abstrusus, Angiostrongylus vasorum and
      Dirofilaria immitis are cardiopulmonary nematodes affecting dogs and cats and
      presently emerging in several countries. The results obtained in 2009 - 2010
      during a study aiming to investigate the occurrence of these nematodes in regions
      from Central (Marche and Abruzzo regions--Sites A and B, respectively) and
      southern (Apulia--Site C) Italy are here reported. A total of 534 and 436
      individual faecal samples collected from dogs and cats were examined, together
      with 471 and 34 faecal environmental samples taken from dog shelters and
      catteries. One hundred and ninety-two individual blood samples were also
      collected from dogs. Faeces were examined using copromicroscopical flotations and
      Baermann technique, whereas blood samples were tested by Knott's method. Eggs of
      C. aerophila were detected in 1.48 % and 20 % (Site A), 8.67 % and 2.71 % (Site
      B), and 16.67 % and 0 % (Site C) of individual and environmental canine samples.
      C. aerophila was found in 2.90 % (Site A), 3.03 % (Site B) and 14.29 % (Site C)
      of individual cats. Larvae of A. vasorum were found in 0.96 % and 2.48 % of
      individual and environmental samples from Site B, respectively, while those of A.
      abstrusus in 1.82 % (Site A) and 9.96 % (Site B) of individual faeces.
      Microfilariae of Dirofilaria immitis, identified on the basis of key
      morphological and morphometric features, were detected in 2.56 % of samples
      collected from Site B. Despite the small sample size, these results indicate that
      cardiopulmonary nematodes occur in Central and southern Italy, thus they should
      be included in the differential diagnosis of pet cardiorespiratory diseases.
      Larger surveys are necessary to gain more information on the diffusion of these
      parasites, especially for C. aerophila and A. vasorum, for which the actual
      distribution is poorly known.

PMID- 21739379
TI  - New insights into morphological and biological features of Capillaria aerophila
      (Trichocephalida, Trichuridae).
AB  - Capillaria aerophila is a trichuroid nematode affecting the respiratory system of
      dogs, cats, wild carnivores and, occasionally, humans. Animals become infected by
      ingesting larvated eggs or earthworms, which act as facultative intermediate
      hosts. The aim of this work is to present new insights into morphological and
      biological features of this neglected lungworm. Typical features of C. aerophila
      eggs, differentiating them from those of most known trichuroid whipworms (i.e.
      size, asymmetry of bipolar plugs and a wall with a network of anastomosing
      ridges), were detected upon light and scanning electron microscopy. Eggs of C.
      aerophila were used for in vitro development. Light microscopy showed typical
      features of C. aerophila eggs: size, asymmetry of bipolar plugs and a wall with a
      network of anastomosing ridges. All these features were confirmed upon SEM, in
      that C. aerophila eggs showed an outer densely striated and net-like shell. Eggs
      of T. vulpis, used for a comparative analysis, were bigger than those of C.
      aerophila and showed a thick and smooth wall at both light and scanning electron
      microscopy. Eggs started to develop after 35 days from shedding and mobile larvae
      were observed in the eggs after two months. The results of this study provide key
      information on the biological cycle of C. aerophila and present key morphological
      characters for the identification of eggs in faeces.

PMID- 21739380
TI  - Comparative efficacy of trichlorphon and trichlorphon/ivermectin combination
      treatment against anthelmintic-resistant cattle nematodes in Argentina.
AB  - Twenty-four Holando Argentino male calves were treated orally with 50 mg/kg body
      weight trichlorphon (TCF); 0.2 mg/kg body weight subcutaneous ivermectin (IVM); a
      combination of TCF+IVM at the same doses and administration routes; or remained
      untreated (control group). All calves were necropsied at day 14 post treatment
      for counting and identification of worms from abomasum, small and large
      intestines and lungs to determine the absolute efficacy (controlled efficacy
      test) for each treatment. Using the faecal egg count reduction test, the efficacy
      was 63.7 % for TCF, 72.3 % for IVM and 99.2 % for TCF+IVM. The absolute efficacy
      of IVM and IVM+TCF was 100 % against Haemonchus placei, Trichostrongylus axei and
      Ostertagia ostertagi (p < 0.05). TCF showed a similar level of efficacy except
      against O. ostertagi (84.7 %). Efficacy of the treatments against Cooperia
      oncophora/pectinata/mcmasteri was 80.4 % for IVM, 95.7 % for TCF and 99.6 % for
      TCF+IVM; against Trichostrongylus colubriformis was 79 % for IVM, 86.2 % for TCF
      and 94.1 % for TCF+IVM; against Nematodirus helvetianus was 0 % for IVM, 100 %
      for TCF and 93.8 % for TCF+IVM. The efficacies of TCF, IVM and TCF+IVM were 100 %
      against Oesophagostomum radiatum and Trichuris spp. The efficacy of TCF against
      Dictyocaulus viviparus was 52 % and 100 % for IVM and IVM+TCF, respectively. This
      is the first report of Trichostrongylus colubriformis and Nematodirus helvetianus
      resistant to ivermectin treatment in cattle of Argentina. The TCF+IVM combination
      could be an alternative for the control and treatment of nematode infections
      including IVM-resistant strains.

PMID- 21739381
TI  - Efficacy of toltrazuril 5 % suspension against Eimeria bovis and Eimeria zuernii
      in calves and observations on the associated immunopathology.
AB  - 16 Calves were each infected with suspensions containing a mixture of
      approximately 230,000 Eimeria bovis and 70,000 E. zuernii oocysts, which resulted
      in detection of oocysts in faeces of 12 of 16 calves by day +14 after infection.
      On day +14 after infection calves were either treated (n = 8) with toltrazuril at
      15 mg/kg body weight or with a placebo. Observations were made on the clinical
      condition, faecal score and liveweight of calves daily from one day post
      infection (pi) until 24 days pi when all calves were euthanised and examined post
      mortem. Samples were collected from ileum and colon for histological,
      immunohistochemical and gene expression studies. The study demonstrated an
      efficacy of toltrazuril for the treatment of E. bovis and E. zuernii infections
      in calves reaching 99 % (based on arithmetic mean oocyst counts in faeces) within
      three days of treatment and remaining at or above this level for six days.
      Toltrazuril did not have a significant effect on the pattern and extent of immune
      cellular infiltration in the mucosa of ileum and colon, but the expression of the
      genes coding IL-2, IL-10 and TNF-alpha in the ileum and TNF-alpha in the colon
      were elevated in calves treated with toltrazuril. Higher levels of oocyst
      shedding were significantly associated with lower expression of genes coding for
      IL-2, IL-10 and higher IP-10. It is concluded that toltrazuril is effective for
      the treatment of coccidiosis due to E. bovis and E. zuernii in calves and enables
      the development of a normal or enhanced immune response to infection.

PMID- 21739382
TI  - Prevalence of Eimeria bovis and Eimeria zuernii in German cattle herds and
      factors influencing oocyst excretion.
AB  - The present study was designed to investigate the prevalence of the pathogenic
      coccidia species E. bovis and E. zuernii in shed-reared animals in German dairy
      and fattening facilities.Samples were obtained from 65 cattle farms distributed
      randomly across all the regions of Germany, regardless of the occurrence of
      clinical problems. The samples were obtained rectally. Faecal consistency and the
      total number of oocysts per gram of faeces (OPG) were determined for Eimeria
      spp., along with the separate OPG values for Eimeria (E.) bovis and E. zuernii. A
      questionnaire was completed for each farm to record information about herd size
      and management together with individual animal data. Eimeria oocysts, regardless
      of the kind of Eimeria spp., were detected in 62 of these farms, which gives a
      prevalence of 95.4 %. The farm prevalence of the pathogenic species was 76.9 %
      for E. bovis and 83.1 % for E. zuernii. The average oocyst excretion level was
      2,950 OPG in terms of total Eimeria spp. oocyst excretion, 700 OPG for E. bovis
      and 1,500 OPG for E. zuernii.The number of oocysts excreted could not be
      correlated significantly with farm type or farm management but depended on the
      floor type which influences the infection pressure, on the age of the calves and
      the time after rehousing. In general, higher oocyst excretion rates were found in
      calves kept on litter compared to rearing on slatted floor. Younger calves and
      calves sampled early after housing shed higher amounts of oocysts than older
      calves and calves stabled a longer period before sampling, respectively.
      Furthermore, there was a positive correlation between OPG and the observation of
      diarrhoea, defined as observation of a loose to liquid faecal consistency.
      Excretion of E. zuernii oocysts was more closely linked to the occurrence of
      diarrhoea than E. bovis oocyst excretion. This study confirms that the pathogenic
      coccidia E. bovis and E. zuernii are ubiquitous in German cattle populations and
      a significant cause of diarrhoeal disease in calf rearing.

PMID- 21739383
TI  - The efficacy of trichlorphon and naphthalophos against multiple anthelmintic
      resistant nematodes of naturally infected sheep in Argentina.
AB  - An anthelmintic efficacy trial was conducted in sheep harbouring anthelmintic
      resistant worms in Argentina. Seventy lambs were selected from a flock that had
      been grazed on pastures infected with trichostrongyles previously shown to be
      resistant to the main anthelmintic groups. Lambs were allocated to comparable
      groups of ten animals each and treated with trichlorphon (50 mg/kg body weight
      (b.w.) orally); naphthalophos (50 mg/kg b.w. orally); ivermectin (0.2 mg/kg b.w.
      subcutaneously); fenbendazole (5 mg/kg b.w. orally); levamisole (8 mg/kg b.w.
      subcutaneously) and closantel (10 mg/kg b.w. orally). There was also an untreated
      group. The dose selection was based on manufacturer's recommendations.Faecal
      samples were collected 0 and 10 days post treatment to estimate efficacy (faecal
      egg count reduction). Six animals from each group were necropsied at day 10 for
      enumeration/identification of worms from the abomasum, small and large intestines
      to determine the absolute efficacy of each agent (controlled efficacy test).
      Trichlorphon and naphthalophos were effective (> 99 %) against Haemonchus
      contortus (p < 0.05).Naphthalophos also showed efficacy against Trichostrongylus
      axei (99.3 %), Teladorsagia circumcincta (97.8 %), Trichostrongylus colubriformis
      (99.2 %), Cooperia punctata/curticei/pectinata (90.4 %), Nematodirus spathiger
      (89.2 %) and Oesophagostomum venulosum/columbianum (93.7 %). Fenbendazole and
      levamisole showed efficacy (> 95 %) against all nematodes except T.
      colubriformis. The efficacy of ivermectin was low against H. contortus (23 %) and
      Cooperia spp. (46.3 %). Closantel showed low efficacy against T. axei (64.4 %),
      H. contortus (80.6 %) and T. colubriformis (59.5 %).When anthelmintic resistance
      is widespread, trichlorphon treatment is appropriate if H. contortus is present;
      however, naphthalophos represents an effective therapeutic alternative for
      incorporation into worm control programmes.

PMID- 21739385
TI  - Isolated dizziness/vertigo, vascular risk factors and stroke.

PMID- 21739384
TI  - Efficacy and safety of the combination imidacloprid 10 % / moxidectin 1.0 % spot
      on (Advocate((r)) spot-on for small cats and ferrets) in the treatment of ear
      mite infection (Otodectes cynotis) in ferrets.
AB  - In this study, the efficacy and safety of a treatment with the combination
      imidacloprid 10 %/ moxidectin 1.0 % spot-on (Advocate((r)) spot-on for small cats
      and ferrets) was tested in 39 ferrets naturally infested with ear mites
      (Otodectes cynotis). The study was performed as a multicentre, non-randomised,
      non-controlled (all study animals were treated) and non-blinded clinical field
      study in two French veterinary practices. Four visits (day (D) 0 = inclusion and
      first treatment, D14 = second treatment, D28 = possible third treatment, D56 =
      termination) were planned. The dosage was one pipet per ferret (designed for cats
      weighing up to 4 kg, corresponding to a dose of moxidectin ranging from 2.2 to 5
      mg/kg body weight) two or three times at 14-days intervals (at D0, D14 and
      possibly D28 depending on the parasitological examination of the ears at D28).
      The main efficacy criterion was the absence of the parasite (all stages incl.
      eggs, larvae, nymphs and adults) from ear scrapings by microscopic examination.
      At D28 after two treatments (D0 and D14), 76.9 % (30/39) of animals were cured.
      Only 23 % (9/39) needed a third treatment. At day 56, 100 % were cured. Local
      symptoms (inflammation and pruritus) were consistently improved (50.6 %
      improvement at D14, 81.0 % at D28 and 97.9 % at D56) as well as the abnormal
      cerumen production (14.7 % improvement at D14, 77.7 % at D28 and 100.0 % at D56).
      No general symptoms were noticed during the study (general health and skin
      aspect). Advocate((r)) spot-on for small cats and ferrets is an effective and
      safe treatment for ear mite infection in ferrets. Two or three treatments
      administered in 14-days intervals to ferrets infested with ear mites provided 100
      % parasitological cure on D56.

PMID- 21739386
TI  - The Registry of Canadian Stroke Network : an evolving methodology.
AB  - Stroke registries can provide information on evidence-based practices and
      interventions, which are critical for us to understand how stroke care is
      delivered and how outcomes are achieved. The Registry of Canadian Stroke Network
      (RCSN) was initiated in 2001 and has evolved over the past decade. In the first
      two years, we found it extremely difficult to obtain informed consent from the
      patient or surrogate which led to selection biases in the registry. Subsequently
      (2003 onwards), under the new health privacy legislation in Ontario, Canada, the
      RCSN was granted special status as a "prescribed registry" which allowed us to
      collect data on all consecutive patients at the regional stroke centres without
      consent. The stroke data was encrypted and all personal contact information had
      been removed, therefore we could no longer conduct follow- up interviews. To
      obtain patient outcomes after discharge, we linked the non-consent-based registry
      database to population-based administrative databases to obtain information on
      patient mortality, readmissions, socioeconomic status, medication use and other
      clinical information of interest. In addition, the registry methodology was
      modified to include a periodic population-based audit on a sample of all stroke
      patients from over 150 acute hospitals across the province, in addition to
      continuous data collection at the 12 registry hospitals in the province. The
      changes in the data collection methodology developed by the RCSN can be applied
      to other provinces and countries.

PMID- 21739387
TI  - [Guidelines for the medical treatment of patients with Alzheimer's disease].
AB  - The prevalence of dementia is approximately 1.7 - 4.3% among aged people in
      Taiwan, and Alzheimer disease (AD) is the most common cause of dementia. Although
      three cholinesterase inhibitors and one glutamate NMDA receptor antagonist are
      available in Taiwan to treat dementia, their insurance reimbursement is strictly
      regulated and only a small proportion of patients with AD receive medical
      treatment. A local consensus of and guideline for treatment of dementia is needed
      in Taiwan. Therefore, the Guideline Subcommittee of the Taiwan Dementia Society
      summarized the data of cholinesterase inhibitors and glutamate NMDA receptor
      antagonist for treatment of the patients with AD according to the principles of
      evidence- based medicine. We have assessed the qualities of studies, levels of
      evidence, and referred to other guidelines proposed by Western countries. After
      several panel discussions, we merged opinions from the subcommittee members and
      proposed a Taiwan consensus.

PMID- 21739388
TI  - The relationship between isolated dizziness/vertigo and the risk factors of
      ischemic stroke: a case control study.
AB  - PURPOSE: Dizziness/vertigo are important public heath care issues especially in
      elderly patients. Isolated dizziness/vertigo without neurological deficits has
      seldom been considered a symptom/sign due to vascular origin. Recently, some
      studies have suggested that vascular origin should be considered in cases of
      positional vertigo and isolated vertigo or dizziness when the etiology remains
      unclear. In this study, we tried to delineate the correlation of
      dizziness/vertigo and risk factors of stroke. METHODS: We collected adult
      subjects receiving health screening of the brain at their own expense. All
      subjects had undergone brain magnetic resonance imaging (MRI), magnetic resonance
      angiography (MRA) and carotid duplex. The chief complaints, body height, body
      weight, waist circumference and blood pressure of all subjects were recorded.
      Most received blood tests including fasting sugar, total cholesterol, low density
      lipoprotein, high density lipoprotein (HDL), triglycerides, and uric acid (UA).
      The relationships between dizziness/vertigo and blood test data, blood pressure,
      body mass index (BMI), waist circumference, metabolic syndrome, carotid duplex,
      silent brain infarction, leukoaraiosis and MRA were analyzed. RESULTS: After
      exclusion, a total of 170 out of 210 subjects were collected. The analysis
      revealed that dizziness/ vertigo had a significant correlation to age, UA , BMI,
      male HDL and female waist circumference. Among them, female waist circumference
      had the highest statistical significance (P = 0.001). Leukoaraiosis on brain MRI
      also had a close relationship with dizziness/vertigo. CONCLUSION: After careful
      examination and approach, a vascular origin should be considered in dizzy
      patients of unknown etiology.

PMID- 21739389
TI  - The clinical characteristics, therapeutic outcome, and prognostic factors of non
      tuberculous bacterial spinal epidural abscess in adults: a hospital-based study.
AB  - PURPOSE: Nontuberculous bacterial spinal epidural abscess (SEA) is a serious
      infectious disease of spines. Despite proper management, SEA remains a disease of
      high morbidity. The epidemiological data in southern Taiwan is still lacking.
      METHODS: We analyzed the clinical features, laboratory data, magnetic resonance
      imaging findings, and therapeutic results of 45 bacterial SEA patients, collected
      during a study period of six years (2003- 2008). RESULTS: The 45 adult SEA
      patients, 32 were men and 13 women, aged 17-81 years (mean = 62 years). Thoracic
      and lumbosacral spines were the most commonly affected segments. Staphylococcus
      aureus was the most commonly implicated pathogen, accounting for infections in
      67% (29/43) of the culture-proven cases, and 41% (12/29) of the S. aureus strains
      were oxacillin resistant. Gram-negative pathogens were implicated in 30% (13/43)
      of the culture-proven cases. Of the 45 patients, 19 underwent antibiotic
      treatment alone and 26 underwent medical and surgical treatments. The therapeutic
      results showed that 28 patients had a good prognosis and 17 had a poor prognosis.
      The significant prognostic factors included higher age, presence of diabetes
      mellitus and chronic heart disease, and initial presentation of altered
      consciousness. CONCLUSION: S. aureus was the most commonly implicated pathogen of
      adult SEA, and most S. aureus strains were oxacillin resistant. A relatively high
      incidence of Gram-negative infection was observed in this study. The
      epidemiological characteristics of the implicated pathogens must receive special
      consideration when selecting the empirical antibiotics. Despite adequate
      management, many adults with bacterial SEA had a high incidence of poor
      prognosis.

PMID- 21739390
TI  - Learning and error patterns in the Chinese Verbal Learning Test in subjects with
      mild cognitive impairment and normal elderly.
AB  - PURPOSE: The discrimination between normal elderly (NC) and those with mild
      cognitive impairment (MCI) is of clinical relevance since the conversion from MCI
      to Alzheimer dementia (AD) is high. METHODS: This study enrolled 216 amnestic MCI
      patients and 103 NC from our memory clinics and assessed whether the learning
      curve, recall and cued scores, as well as error patterns from the Chinese Version
      Verbal Learning Test (CVVLT) helped to distinguish between these two groups.
      RESULTS: Our results revealed that subjects with MCI had a lower rate of
      acquisition and deceleration of learning in the learning curve. The MCI group
      also showed a lower retention rate and recall scores as compared with the NC
      group. Further, the error patterns offered discrimination values between the two
      groups in total number of perseverations, intrusion in the cued recall, as well
      as prototypic and unrelated errors in recognition. An inverse correlation was
      seen between memory scores and error patterns. CONCLUSION: This study suggests
      that by combining the learning and error patterns from the verbal memory test,
      patients with MCI can be better differentiated from normal elderly.

PMID- 21739391
TI  - Brain abscess associated with cerebral amyloid angiopathy and hemorrhage.
AB  - PURPOSE: We want to report an extremely rare condition, brain abscess associated
      with cerebral amylid angiopathy and hemorrhage. CASE REPORT: We report on a 64
      year-old woman who presented initially with moderate fever and headache. She was
      initially misdiagnosed with a bleeding tumor or arteriovenous malformation
      rupture and treated without antibiotic therapy. The mass was surgically drained
      due to neurological deterioration on day 14 after admission. Streptococcus
      virdians was isolated from the pus culture. The pathology evaluation showed
      cerebral amyloid angiopathy. She received intravenous antibiotic therapy for 4
      weeks. She was eventually discharged home with left quadrantanopia. CONCLUSION:
      This case reminds us early recognition of brain abscess formation at the site of
      intracerebral hemorrhage is very important for prompt and appropriate treatment
      to improve the overall prognosis.

PMID- 21739392
TI  - Subacute combined degeneration caused by nitrous oxide intoxication: case
      reports.
AB  - PURPOSE: Case reports with a comprehensive review of the current literature
      concerning subacute combined degeneration induced by nitrous oxide inhalation. A
      differential diagnosis should be considered when young patients present with
      progressive myelopathy because that the misuse of nitrous oxide has potentially
      serious outcomes. CASES REPORT: Three young patients aged from 18 to 24, one male
      and two females, were diagnosed with progressive ascending numbness in four limbs
      or both legs and ataxia. They all had been inhaling nitrous oxide from whipped
      cream containers for several months. A cervicothoracic magnetic resonance imaging
      scan revealed long segmental hyperintensity changes at the posterior column of
      the spinal cord. Serological examination showed a low level of vitamin B12.
      Subacute combined degeneration of the spinal cord was diagnosed and the etiology
      was considered related to nitrous oxide misuse. Their neurological status,
      neuroimage, and neurophysiologic condition improved after vitamin B12
      supplementation and cessation of nitrous oxide inhalation. CONCLUSION: Iatrogenic
      usage of nitrous oxide apparently resulted in subacute combined degeneration in
      our three patients. Recently, nitrous oxide misuse has increased among young
      people. Subacute combined degeneration of the spinal cord should be considered as
      a possible outcome of such abuse.

PMID- 21739393
TI  - Foodborne botulinum type E intoxication associated with dried bean curd: first
      case report in Taiwan.
AB  - PURPOSE: Botulism type E intoxication is a rare condition among human botulism.
      We aim to describe a first case of botulism type E intoxication in Taiwan. CASE
      REPORT: We report a 36-year-old young man with foodborne botulism type E
      associated with commercially vacuum packaged dried bean curd. He developed
      bilateral ptosis, diplopia and dysphagia 4 days after taking the dried bean curd.
      Electrophysiologic findings demonstrated waxing responses to 3 Hz repetitive
      nerve stimulation and decreased compound muscle action potentials on peripheral
      nerve conduction study. A bioassay for botulism in mice demonstrated that the
      patient had botulism caused by type E botulinum toxin. Antibodeis to C. botulinum
      type E were identified from his serum, confirming the diagnosis. CONCLUSIONS:
      This is the first known case of foodborne type E botulism in Taiwan. The
      potential source of this foodborne botulism should consider contaminated food
      made of soy beans.

PMID- 21739394
TI  - Spinal neurosarcoidosis.
AB  - PURPOSE: Neurosarcoidosis is a multisystemic disorder and is rare in Taiwan.
      Diagnosis of neurosarcoidosis depends on the clinical features, neuroimage
      studies and the pathological findings of non-caseous granuloma in various
      tissues. CASE REPORT: A 62-year-old woman had diabetic mellitus and an old
      lacunar stroke in 1996. In 2003, she received steroid therapy for one year for
      the mediastinal mass lesion with a good response. In June 2006, she suffered from
      band-like numbness and muscle weakness descending from the abdomen to bilateral
      lower extremities and urinary difficulty. Spinal magnetic resonance imaging
      showed an intramedullary lesion in C6~C7 region. The chest computed tomography
      (CT) scan revealed multiple small and enlarged nodes over the mediastinal regions
      compared with the previous chest CT in 2005. The pathological changes of the
      mediastinal mass demonstrated non-caseous granulomatous changes. Therefore,
      probable cervical neurosarcoidosis was impressed. After an intravenous
      dexamethasone followed by oral steroid treatment, her symptoms and signs had
      gradually improved. A follow-up spinal magnetic resonance imaging showed an
      improvement of the cervical cord lesion. CONCLUSION: Spinal neurosarcoidosis can
      mimic a spinal tumor, an inflammatory lesion, or even a demyelinating lesion in
      both clinical and neuroimaging studies. A high index of suspicion of sarcoidosis
      is required for an early diagnosis, and steroid therapy is usually associated
      with a favorable outcome.

PMID- 21739395
TI  - Spontaneous dissection of the vertebral artery: report of three cases.
AB  - PURPOSE: Vertebral artery dissection (VAD), although uncommon, is an important
      cause of ischemic stroke in young adults. Without prompt diagnosis and treatment,
      it may cause mortality and morbidity. Spontaneous VAD related to abrupt neck
      position change, sudden sneezing, or severe cough and vomiting after fish bone
      choking are rarely reported. This report describes three cases of spontaneous VAD
      due to seemingly harmless events. CASE REPORT: The first patient developed
      vertebro-basilar ischemic symptoms after suddenly turning his head to the left
      during an argument with a colleague. The second suffered from right lateral
      medullary infarction after sudden sneezing. The third developed left lateral
      medullary syndrome after she tried to extract a fish bone in her throat, which
      induced severe cough and vomiting. The three cases all presented with acute
      severe neck pain with posterior circulation ischemic symptoms and signs. Magnetic
      resonance imaging (MRI), magnetic resonance angiogram (MRA), and conventional
      angiography confirmed the diagnosis. The first patient was treated with warfarin
      and recovered well. The other two cases received heparinization and then oral
      anticoagulant therapy, and recovered without residual neurologic deficits.
      CONCLUSION: In conclusion, VAD should be among the differentials considered when
      encountering young patients presentation with such clinical symptoms.

PMID- 21739396
TI  - Amyloid neuropathy with transthyretin mutations: overview and unique Ala97Ser in
      Taiwan.
AB  - Familial amyloid polyneuropathy (FAP) is a major etiology in differential
      diagnosis of symmetric axonalform polyneuropathy, but had been considered an
      unusual disease in Taiwan. We have reviewed the pathology of nerve biopsies and
      sequenced the entire 4 exons of transthyretin (TTR), the most common genetic
      mutation of FAP. Our studies indicated that the mutation of TTR at Ala97Ser (TTR
      Ala97Ser) was a new mutation only reported in ethnic Taiwanese, and this mutation
      accounted for the most frequent etiology of adult-onset pan-modality (involving
      motor, sensory, and autonomic components of peripheral nerves) polyneuropathy
      with the pathology of axonal degeneration type. Over the past 10 years, there
      have been advancements in the management of FAP due to TTR mutations: (1)
      symptomatic treatments of dyaautonomia, especially orthostatic hypotension, and
      (2) therapies with liver transplantation and small molecules to reduce or
      stabilize TTR.

PMID- 21739397
TI  - Stroke due to late in-stent thrombosis following carotid stenting.

PMID- 21739398
TI  - [Acute angle closure, chronic angle-closure glaucoma and their differential
      diagnoses].

PMID- 21739399
TI  - [Ophthalmological oncology].

PMID- 21739400
TI  - [Intraocular manifestations of systemic neoplasms].
AB  - There are multiple possible intraocular manifestations in patients with systemic
      neoplasms. At first line there are uveal, retinal and vitreous metastases from
      carcinomas, melanomas and lymphomas. In patients with von Hippel Lindau syndrome
      or familiar adenomatous polyposis coli (FAP), Gardner or Turcot syndromes, fundus
      examinations can help in the primary diagnosis and thereby facilitate the early
      detection of systemic neoplasms such as cerebral and spinal haemangioblastoma,
      kidney or bowel cancer. Furthermore there are rare ocular paraneoplastic
      syndromes such as the cancer- or melanoma-associated retinopathies (CAR/MAR), the
      paraneoplastic optic neuropathy (PON) and the bilateral diffuse melanocytic
      proliferation (BDUMP) that develop secondary to systemic malignancies and can be
      the primary manifestation.

PMID- 21739401
TI  - [New developments in molecular genetics and treatment of retinoblastoma].
AB  - Retinoblastomas are the most frequent primary malignant intraocular tumours
      worldwide. Conventional and new treatment modalities have significantly improved
      the chance for survival and preservation of vision. The armamentarium of
      treatment modalities has been broadened recently by new techniques like
      intraarterial chemotherapy, which still has to be considered as experimental
      since long-term follow-up results are not yet available. The excellent prognosis
      for retinoblastomas in countries with a well developed health system is
      contrasted by the miserable prognosis for retinoblastomas in developing
      countries, which must be changed by a joint effort of all centres.

PMID- 21739402
TI  - [Should we abandon the eponym 'Wegener's granulomatosis'? A historical
      excursion].

PMID- 21739403
TI  - [Adolf Hitler's eyes].

PMID- 21739404
TI  - Prenatal MR diffusion tractography in a fetus with complete corpus callosum
      agenesis.
AB  - Diffusion tensor imaging (DTI) in combination with 3D-tractography
      reconstructions allows studying the neuro-architecture of complex brain
      malformations in vivo. Prenatal, in utero DTI has been limited by long
      acquisition times, poor signal to noise ratio and multiple artifacts. Recent
      developments in hard- and software allow collection of high quality DTI data sets
      in utero. We report on the DTI and tractography data of a fetus with a corpus
      callosum agenesis. Our case shows that nowadays the neuro-architecture of the
      fetal brain can be studied in excellent detail. Prenatal DTI and tractography may
      help to improve our understanding of complex brain malformations.

PMID- 21739405
TI  - Endovascular treatment of symptomatic radiation-induced basilar artery stenosis
      25 years after medulloblastoma.
AB  - Intracranial stenosis as late sequela after cerebral radiation therapy for
      medulloblastoma is an exceptionally rare finding. We report for the first time a
      case of 31-year-old patient with a history of medulloblastoma 25 years ago and
      now presenting with radiation-induced high-grade basilar stenosis and recurrent
      ischemic symptoms despite best medical therapy. The stenosis was treated
      successfully with angioplasty followed by stenting using a self-expandable
      microstent. Additionally, MRI revealed multiple cavernomas, illustrating that
      radiation-induced microbleeds may occur.

PMID- 21739406
TI  - Assessing quality of life in long-term survivors after 125I brachytherapy for low
      grade glioma in childhood.
AB  - Quality of life (QOL) is important for the survivors of malignancies. We
      investigated health-related QOL in 51 patients treated with iodine-125 (125I)
      brachytherapy for childhood low-grade gliomas. Instruments included a
      questionnaire on life situation, German versions of PEDQOL (8-18 years), EORTC
      QLQ-30 and head and neck module H&N-35 (>18 years), strength and difficulties
      questionnaire, "Fertigkeitsskala Munster Heidelberg", and an adapted Rankin
      score. The time lapsed since 125I-brachytherapy was 134 months (median, range: 29
      293 months). 57% of the patients were over 18 years of age, 34% were 11-17 years
      old and 8% were younger. 14 had undergone other treatments after 125I
      brachytherapy. Over half of the >18 year olds reported residual problems; 68%
      were disabled, 38% to a severe degree. Many of the young adults still lived with
      their parents and 17% were jobless. 43% of the children/adolescents needed
      rehabilitative treatment, 20% visited special schools and 71% were disabled, 33%
      severely. The patients and their caregivers rated their QOL as not different from
      that of the normal population. However, many QOL dimensions correlated to the
      severity of disability. Comparison of QOL outcomes between different treatment
      measures would require a prospective study controlling for the most important
      factors of influence.

PMID- 21739407
TI  - [Pathways-to-Care for First-Episode psychotic patients--an overview of
      international studies].
AB  - A longer duration of untreated psychosis (DUP) as well as of untreated illness
      (DUI) was found to be associated with a negative course of psychosis. Thus,
      increasing efforts are made to reduce the DUP and provide adequate treatment as
      early as possible. But, in order to overcome obstacles to early help-seeking,
      these have to be identified first. Thus, an overview on initial help-seeking
      behaviour and predictors of DUP is given. Across 25 identified studies, the DUP,
      at about one year on average, is still unfavourably long and includes on average
      of three help-seeking contacts prior to the initiation of adequate treatment.
      Since negative factors in pathways-to-care involve features on all relevant
      levels (patient, social environment and health-care system), an optimisation of
      pathways-to-care will require the integration of services and continuous
      awareness programmes targeting the general population and mental health-care
      professionals.

PMID- 21739408
TI  - [How does maternal alcohol consumption during pregnancy affect the development of
      attention deficit/hyperactivity syndrome in the child].
AB  - Besides genetic susceptibility, environmental factors and gene-environment
      interactions are of central interest in research on attention
      deficit/hyperactivity disorder in children. Focusing on maternal behaviour during
      pregnancy, prenatal maternal alcohol consumption is associated with behavioural
      disorders in children. In animal models, developmental disorders of brain
      structures as well as subsequent behavioural disorders - similar to findings in
      attention deficit disorder - were caused by prenatal alcohol exposure. These
      findings occur in small rodents (mice, rats) as well as in primates and can be
      caused by even moderate alcohol exposure. In foetal alcohol syndrome (FAS) and
      foetal alcohol spectrum disease (FASD) in humans, symptoms like hyperactivity,
      disruptive or impulsive behaviour along with reduced attention and slower
      reaction time are observed. These findings resemble the symptoms of ADHD. For
      that reason, children diagnosed with FAS/FASD are frequently diagnosed with ADHD
      in parallel. Even small amounts of alcohol during pregnancy are responsible for
      cognitive and behavioural impairments like a significantly decreased IQ. About 50
      % of adult ADHD patients show alcohol abuse or dependency and/or other substance
      disorders. Due to this, a higher rate of prenatal exposition to psychoactive
      substances for children of mothers affected with ADHD seems probable. However,
      there are no sufficient data on ADHD and its association to substance abuse in
      pregnancy, which makes it difficult to quantify the impact of genetic and
      environmental causes for the development of childhood ADHD. So far, no link could
      be proven with a high level of evidence between moderate prenatal alcohol
      consumption and the development of childhood ADHD. It has to be recognised that
      all present studies are based on self-reported alcohol consumption. Data
      collected by this methodology are usually severely biased to an underestimation
      of alcohol abuse. Objective tests for alcohol abuse in pregnancy, such as the
      analysis of fatty acid ethyl esters or ethyl glucuronide in foetal feces after
      birth, show rates of alcohol consumption in pregnant women which are dramatically
      higher than reported. Therefore, studies investigating the association between
      prenatal alcohol exposure and ADHD should incorporate the analysis and validation
      of more objective methods, such as parameters for alcohol degradation.

PMID- 21739409
TI  - Closed traumatic brain injury model in sheep mimicking high-velocity, closed head
      trauma in humans.
AB  - To date, there are only a few, non-evidence based, cerebroprotective therapeutic
      strategies for treatment and, accordingly, for prevention of secondary brain
      injuries following severe closed head trauma. In order to develop new therapy
      strategies, existing realistic animal models need to be advanced. The objective
      is to bridge standardized small animal models and actual patient medical care,
      since the results of experimental small animal studies often cannot be
      transferred to brain-injured humans. For improved standardization of high
      velocity trauma, new trauma devices for initiating closed traumatic brain injury
      in sheep were developed. The following new devices were tested: 1. An
      anatomically shaped rubber bolt with an integrated oscillation absorber for
      prevention of skull fractures; 2. Stationary mounting of the bolt to guarantee
      stable experimental conditions; 3. Varying degrees of trauma severity, i. e.,
      mild and severe closed traumatic brain injury, using different cartridges; and 4.
      Trauma analysis via high-speed video recording. Peritraumatic measurements of
      intracranial pressure, brain tissue pH, brain tissue oxygen, and carbon dioxide
      pressure, as well as neurotransmitter concentrations were performed. Cerebral
      injuries were documented with magnetic resonance imaging and compared to
      neuropathological results. Due to the new trauma devices, skull fractures were
      prevented. The high-speed video recording documented a realistic trauma mechanism
      for a car accident. Enhancement of extracellular glutamate, aspartate, and gamma
      amino butyric acid concentrations began 60 min after the trauma. Magnetic
      resonance imaging and neuropathological results showed characteristic injury
      patterns of mild, and severe, closed traumatic brain injury. The severe, closed
      traumatic brain injury group showed diffuse axonal injuries, traumatic
      subarachnoid hemorrhage, and hemorrhagic contusions with inconsistent
      distribution among the animals. The model presented here achieves a gain in
      standardization of severe, closed traumatic brain injury by increasing
      approximation to reality. The still existent heterogeneity of brain pathology
      mimics brain changes observed in patients after high-energy trauma. This model
      seems to close the gap between experimental small animal models and clinical
      studies. However, further investigations are needed to evaluate if this model can
      be used for testing new therapeutic strategies for these patients.

PMID- 21739410
TI  - Minimizing brain shift during functional neurosurgical procedures - a simple burr
      hole technique that can decrease CSF loss and intracranial air.
AB  - BACKGROUND: Exact stereotactic placement of deep brain stimulation electrodes
      during functional stereotactic neurosurgical procedures can be impeded by
      intraoperative brain shift. Brain shift has been shown to correlate with the
      amount of intracranial (subdural) air detected on early postoperative imaging
      studies. We report a simple burr hole technique that reduces the loss of
      cerebrospinal fluid (CSF) and has the potential to significantly reduce the
      amount of postoperative intracranial air. MATERIAL AND METHODS: A total of 16
      patients were studied with half (group 2) receiving the burr hole technique
      designed to seal the CSF space and thereby reducing CSF loss. The other 8
      patients (group 1) received the standard burr hole technique. The 2 groups were
      of similar age, gender, diagnosis (Parkinson's disease, n=14; cervical dystonia
      n=2), and surgical targets. All patients received bilateral electrodes either in
      the subthalamic nucleus (STN, n=14) or in the globus pallidum internus (GPi, n=2)
      avoiding transventricular trajectories. Early postoperative 3-dimensional
      computed tomography (3D CT) was used to check for possible bleeding, DBS lead
      location, and the amount of intracranial air. Intracranial air was assessed
      manually in a volumetric slice-by-slice approach in the individual postoperative
      CT and the groups compared by t-test. RESULTS: Group 2 showed significantly lower
      postoperative intracranial air volumes (4.86 +/- 4.35cc) as compared to group 1
      (27.59 +/- 17.80 cc, p=0.0083*). The duration of surgery, however, was
      significantly longer for group 1 (435 +/- 56.05 min) as compared to group 2 (316
      +/- 34.79 min,p=0.00015*).The time span between the conclusion of the operation
      and postoperative 3DCT was similar for both groups. CONCLUSION: This new and
      simple burr hole technique was associated with a significant reduction in
      postoperative intracranial air. Reduction of intracranial air will ultimately
      reduce brain shift. That total operation time does not influence intracranial air
      is discussed as well as the limitations of this pilot series. In the authors'
      opinion, this straightforward and cost-effective technique has the potential to
      reduce brain shift and to increase DBS placement accuracy during functional
      stereotactic neurosurgical procedures performed in the seated or half-sitting
      position. A larger more standardized patient series is necessary to substantiate
      the findings.

PMID- 21739411
TI  - [Clinical trials with medical devices: lack of quality illustrated for faecal
      incontinence].
AB  - BACKGROUND: Medical devices must be safe and functioning states the law.
      Treatments with medical devices need not be efficacious to be allowed. We
      investigated special requirements and problems arising from the law. METHODS: The
      market for medical devices is contrasted with that for drugs. The requirements of
      relevant laws are discussed. Finally, published clinical studies on anal
      incontinence are analysed with respect to their methodological quality. RESULTS:
      Clinical trials of medical devices for treat-ing anal incontinence are of poor
      methodological quality thus preventing evaluation of the devices' utility.
      CONCLUSION: Large, high quality clinical studies of the efficacy of medical
      devices for treating anal incontinence are urgently needed. Only such studies
      enable health technology assessment and comprehensible decisions on reimbursement
      by health insurance.

PMID- 21739412
TI  - [Consequences drawn from the evaluation of logbook-based surgical training for
      final year students].
AB  - BACKGROUND: The current training programme for final year medical students does
      not meet the requirements of surgery and is obviously not able to encourage young
      physicians to become surgeons. After finishing the surgical trimester, the
      motivation to become a doctor decreases considerably more strongly than after any
      other specialty during the final year programme. This emphasises the urgent need
      for a consequent redesign involving modern educational programmes. METHOD: The
      present article represents a systematic analysis of 70 logbooks used by final
      year medical students, which accompanied them during the surgical trimester from
      August 2008 to December 2009 at the Department of Surgery at the University of
      Greifswald, Germany. This analysis was subsequently compared to an evaluation of
      the same students as to how valuable the logbook was for their surgical education
      by means of an anonymous questionnaire. RESULTS: The results indicate that the
      general quality of education during the surgical trimester was evaluated to be
      high, but that the use of a logbook in the current mode did not contribute to
      enhance medical/surgical training programmes. Although most of the requested
      examinations and procedures were carried out by at least 70 % of the students,
      less than half of them had the impression that the use of this specific logbook
      improved their education. The students ask for a more intense interaction with
      the tutor/mentor and request differentiated discussions about their personal
      stronger and weaker spots, as well as more bedside teaching, e. g., the terms of
      training ward rounds with the consultant surgeon. Besides, they demand more
      supervised practical skill training in contrast to the often commonly practiced
      "learning by doing". CONCLUSION: The logbook is a powerful and effective
      educational tool able to structure and examine medical training and skills. But
      the present evaluation of the surgical logbook indicates that there is a need to
      adapt the current version to student's and institution's requirements. Otherwise
      it will only be seen as a purely labour intensive obligation, which will
      consequently lead to frustration and will not enrich the surgical training
      programme within the final year of medical school.

PMID- 21739413
TI  - [9th  Gera conference: longitudinal and radial endosonography with interventions 
      reflections of the organiser and participants].

PMID- 21739414
TI  - [Modified mesh implantation technique for a large paraoesophageal type  III
      hernia].

PMID- 21739415
TI  - [Gender-specific evaluation of student's career planning during medical study in
      terms of orthopaedic trauma].
AB  - BACKGROUND: Due to recent changes in the medical licencing act as well as to the
      introduction of a new model-course programme for medical studies, careers in
      medicine have become increasingly more attractive. However, there is still a
      dramatic shortage in younger generation physicians, especially within the
      surgical fields. The goal of this cross-sectional study was the gender-specific
      assessment of the ideal career wishes of students during medical school, with a
      focus being placed in orthopaedic trauma surgery. MATERIALS AND METHODS: During
      the winter semester of 2010/2011 an online questionnaire (www.surveymonkey.com)
      was created for students enrolled in their 3rd to 12th semester (n=887). The
      questionnaire consisted of 50 questions [Likert scale (LS); 5 = agree, 1 =
      disagree] along with 10 free response questions. The scope of these questions
      ranged from personal career goals, within the context of their learning
      environment, to general life goals and planning. With regard to career choice, a
      differentiation was made between students' ideal career choices/subjects (IS),
      which were based solely on personal affinity, and so-called reality-based
      subjects (RS), which students considered more practical and to which they were
      more likely to apply in the future. RESULTS: The response rate was 36,4% (n=323,
      23,4 years, 6.3 semesters, 226 [70.0%] female [f] and 97 [30.0%] male [m]). A
      total of 206 students (63.8%; m=55.7% vs. f=66.7%; p=0.047) were able to pinpoint
      an IS, this percentage increased with increasing semester number (p=0.048).
      Overall, 29.1% of students indicated that their IS lay in the field of
      orthopaedic trauma, while 20.0% of men and 19.1% of women saw it as a realistic
      career path (RS). Throughout the course of their studies, from the 3rd semester
      to their practical year, a declining tendency was observed regarding the
      agreement between ideal and realistic career paths. Particularly evident was a
      decreasing interest in the field of orthopaedic trauma, beginning around the 9th
      semester and during the practical year, especially among the female student
      population. The reason for this shift seems multifactorial, ranging from concerns
      about family planning as well as the work load in a male-dominated field. By the
      time students enter their practical year, 13.5% of women and 15.4% of men were
      still certain in their choice to pursue a career in orthopaedic trauma (RS).
      CONCLUSIONS: It seems that there is great interest in the fields of orthopaedic
      trauma among both female and male students in the middle portion of their
      studies. Women, especially, tend to prefer a specialisation in this operative
      field early in the course of their studies. However, this pool of potential
      successors decreases dramatically with time, due to personal experiences garnered
      on the wards, expectations regarding career paths (male-dominated, long hours) as
      well as concerns about family planning. The most dramatic shift seems to occur
      during the practical year.

PMID- 21739416
TI  - Antipsychotics and venous thromboembolism risk: a meta-analysis.
AB  - BACKGROUND: Antipsychotics have been inconclusively implicated in susceptibility
      to venous thromboembolism (VTE). OBJECTIVES AND METHODS: The aim of this study
      was to investigate the association between antipsychotic drugs and VTE risk by a
      meta-analysis. PubMed and EmBASE databases were searched for publications through
      to 10 October 2010. Statistical analysis was performed using Revman 4.2 and Stata
      10.0 software. RESULTS: 7 case-control studies involving 31 095 cases and 143 472
      controls were analyzed. The results indicate that antipsychotic exposure confers
      a 139 % increased risk of VTE (odds ratio [OR] = 2.39, 95 % confidence interval
      [CI]:1.71-3.35). Pooled estimates by drug type showed that use of low-potency
      antipsychotics (OR = 2.91, 95 % CI 1.80-4.71) is the most important risk factor
      for VTE, followed by atypical (OR = 2.20, 95 % CI 1.22-3.96), conventional (OR =
      1.72, 95 % CI 1.31-2.24) and high-potency drugs (OR = 1.58, 95 % CI 1.50-1.67).
      CONCLUSIONS: This meta-analysis suggests that antipsychotics are a risk factor
      for VTE. Additional studies in large cohorts are required to validate our
      findings. Future analyses should study potential eff ect modifications by
      different doses and durations of antipsychotic exposure in different populations.

PMID- 21739417
TI  - Simultaneous cardiac and lung surgery for incidental solitary pulmonary nodule:
      learning from the past.
AB  - BACKGROUND: Incidental solitary pulmonary nodules (ISPN) detected prior to
      scheduled cardiac surgery are rare but challenging. We evaluated the long-term
      outcome of patients with ISPN undergoing simultaneous cardiac and lung surgery.
      METHODS: The clinical records of 33 consecutive patients with ISPN undergoing
      cardiac and lung surgery, either simultaneously (n = 30) or sequentially (n = 3),
      were retrospectively evaluated and completed by detailed follow-up. RESULTS: On
      histological examination, 14 cases (42.4%) of primary NSCLC were identified.
      Benign findings consisted mostly of hamartoma and inflammation. Malignant ISPN
      were larger in size (22.5 +/- 12.4 vs. 13.6 +/- 8.6 mm) and ISPN with a diameter
      >10 mm had a higher incidence of malignancy compared to those <=10 mm (56.0% vs.
      0%). Patients undergoing concomittant heart and lung surgery received either a
      wedge resection (n = 26) or a lobectomy (n = 4). The 5-year survival of patients
      with malignant ISPN was lower than that of patients with benign ISPN (43.6% vs.
      85.6%). CONCLUSIONS: Our results corroborate a high incidence of malignancy in
      ISPN detected prior to scheduled cardiac surgery. Simultaneous cardiac and lung
      surgery for NSCLC appears to be associated with a poor long-term outcome.

PMID- 21739418
TI  - Association between functional IRF7 variant and systemic lupus erythematosus may
      need more critical examination: comment on the article by Fu et al.

PMID- 21739420
TI  - Genetic variants in the HLA-DRB1 gene are associated with Kashin-Beck disease in
      the Tibetan population.
AB  - OBJECTIVE: To investigate the association between variants in the HLA-DRB1 gene
      and Kashin-Beck disease (KBD), as well as associations of selenium and iodine
      deficiencies with KBD in a Tibetan population. METHODS: Fourteen single
      nucleotide polymorphisms (SNPs) were genotyped around the HLA-DRB1 gene, and HLA
      DRB1 allele genotyping was performed in a discovery cohort, composed of 605
      patients with KBD and 393 control subjects, and/or a replication cohort, composed
      of 290 patients with KBD and 295 controls. Plasma concentrations of selenium and
      iodine were measured and compared by t-test in 299 patients with KBD and 280
      controls from the same villages. RESULTS: Four SNPs (rs6457617, rs6457620,
      rs9275295, and rs7745040) in the HLA-DRB1 gene locus were significantly
      associated with KBD in both the discovery cohort and replication cohort (combined
      cohort odds ratios [ORs] 1.307-1.402, P = 0.0039-0.0006). The protective
      haplotype GTCC and the risk haplotype ACGT, each generated by the 4 SNPs, showed
      a significant association with KBD (for GTCC, OR 0.77, P = 0.0031; for ACGT, OR
      1.40, P = 0.0014). HLA-DRB1 allele genotyping revealed that the frequencies of
      HLA-DRB1*08 and *11 were significantly different between patients with KBD and
      controls (for HLA-DRB1*08, OR 0.731, P = 0.00564; for HLA-DRB1*11, OR 0.489, P =
      0.000395). Moreover, plasma concentrations of selenium and iodine were
      significantly different between patients with KBD and controls from the same
      villages (P = 0.0013 and P = 1.84 * 10(-12) , respectively). CONCLUSION: These
      findings, obtained in plasma samples from Tibetan patients with KBD and healthy
      control subjects from the same regions, confirm the role of selenium and iodine
      deficiencies in the development of KBD. Moreover, genetic variants in the HLA
      DRB1 gene significantly increase the susceptibility to KBD in this population.

PMID- 21739421
TI  - Autoimmunity and inflammation are independent of class II transactivator type PIV
      dependent class II major histocompatibility complex expression in peripheral
      tissues during collagen-induced arthritis.
AB  - OBJECTIVE: To determine the regulation of class II major histocompatibility
      complex (MHC) expression in fibroblast-like synoviocytes (FLS) in order to
      investigate their role as nonprofessional antigen-presenting cells in collagen
      induced arthritis (CIA). METHODS: Expression of class II MHC, class II MHC
      transactivator (CIITA), and Ciita isoforms PI, PIII, and PIV was examined by real
      time quantitative polymerase chain reaction, immunohistochemistry, and flow
      cytometry in human synovial tissues, arthritic mouse joints, and human and murine
      FLS. CIA was induced in mice in which isoform PIV of Ciita was knocked out (PIV(
      /-) ), in PIV(-/-)  mice transgenic for CIITA in the thymus (K14 CIITA), and in
      their control littermates. RESULTS: HLA-DRA, total CIITA, and CIITA PIII
      messenger RNA levels were significantly increased in synovial tissue samples from
      patients with rheumatoid arthritis compared with the levels in tissue from
      patients with osteoarthritis. Human FLS expressed surface class II MHC via CIITA
      PIII and PIV, while class II MHC expression in murine FLS was entirely mediated
      by PIV. Mice with a targeted deletion of CIITA PIV lack CD4+ T cells and were
      protected against CIA. The expression of CIITA was restored in the thymus of PIV(
      /-)  K14 CIITA-transgenic mice, which had a normal CD4+ T cell repertoire and
      normal surface levels of class II MHC on professional antigen-presenting cells,
      but did not induce class II MHC on FLS. Synovial inflammation and immune
      responses against type II collagen were similar in PIV(-/-)  K14 CIITA-transgenic
      mice and control mice with CIA, but bone erosion was significantly reduced in the
      absence of PIV. CONCLUSION: Overexpression of class II MHC is tightly correlated
      with CIITA expression in arthritic synovium and in FLS. Selective targeting of
      Ciita PIV in peripheral tissues abrogates class II MHC expression by murine FLS
      but does not protect against inflammation and autoimmune responses in CIA.

PMID- 21739422
TI  - Coexpression of chemokine receptors CCR5, CXCR3, and CCR4 and ligands for P- and
      E-selectin on T lymphocytes of patients with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate P- and E-selectin ligand coexpression with chemokine
      receptors (CKRs) on T cells in the synovial fluid (SF) and blood of children with
      juvenile idiopathic arthritis (JIA). METHODS: Sixteen patients with polyarticular
      or persistent oligoarticular JIA (ages 5.3-15.1 years) were studied. SF and
      venous blood were collected, and immunostaining for the expression of CCR4, CCR5,
      CXCR3, and P- or E-selectin ligands was performed. RESULTS: Compared to blood, SF
      was greatly enriched for CD4+ T cells bearing CCR5, CCR4, CXCR3, and both P- and
      E-selectin ligand. Twenty-five percent of the CD4+ T cells in SF expressed both
      CCR5 and CCR4, some also coexpressing CXCR3. Such cells were rare in blood. Half
      of the few CCR5+ T cells in blood coexpressed P- or E-selectin ligand, a
      phenotype that was enriched up to 50-fold in SF. A minority of CCR4+ and CXCR3+
      cells in blood (~25%) coexpressed selectin ligand; these were enriched 4-8-fold
      in SF. Most CCR4-expressing CD4+ T cells expressed both E-selectin ligand and
      cutaneous lymphocyte antigen. CONCLUSION: CCR4-, CCR5-, CXCR3-, and selectin
      ligand-expressing CD4+ T cells preferentially accumulate in the joints of
      children with JIA. The marked enrichment of CCR5+ T cells coexpressing P-selectin
      and/or E-selectin ligand in CD4+ SF T cells suggests that the few such cells in
      blood selectively migrate to inflamed joints via endothelial P- and E-selectin-
      and CCR5-activating chemokines. The predominance of CCR4-expressing CD4+ T cells
      coexpressing E-selectin ligand suggests that such cells migrate not only to areas
      of cutaneous inflammation, as previously reported, but also to the joints in JIA.
      Combined targeting of CCR5- and E-selectin-dependent mechanisms may be a relevant
      treatment strategy.

PMID- 21739423
TI  - Remission of rheumatoid arthritis in clinical practice: application of the
      American College of Rheumatology/European League Against Rheumatism 2011
      remission criteria.
AB  - OBJECTIVE: To describe use of the American College of Rheumatology/European
      League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission
      criteria in clinical practice. METHODS: Remission was examined using data on
      1,341 patients with RA (91% men) from the US Department of Veterans Affairs RA
      (VARA) registry (total of 9,700 visits) and 1,153 patients with RA (25.8% men) in
      a community rheumatology practice (Arthritis and Rheumatology Clinics of Kansas
      [ARCK]) (total of 6,362 visits). Cross-sectional and cumulative probabilities
      were studied, and agreement between the various remission criteria was assessed.
      Aspects of reliability of the criteria were determined using Boolean-based
      definitions, as well as the Clinical Disease Activity Index (CDAI) and Simplified
      Disease Activity Index (SDAI) scoring methods proposed by the ACR/EULAR joint
      committee. RESULTS: When the 3-variable ACR/EULAR definition of remission
      recommended for use in community practice (swollen and tender joint counts <=1,
      and visual analog scale score for patient's global assessment of disease activity
      <=1) was applied, cross-sectional remission was 7.5% (95% confidence interval
      [95% CI] 6.4, 8.7%) for ARCK and 8.9% (95% CI 7.9, 9.9%) for VARA, and cumulative
      remission (remission at any observation) was 18.0% (for ARCK) and 24.4% (for
      VARA), over a mean followup of ~2.2 years. Addition of the erythrocyte
      sedimentation rate or C-reactive protein level to the criteria set reduced
      remission to 5.0-6.2%, and use of the CDAI/SDAI increased the proportions to 6.9
      10.1%. Moreover, 1.8-4.6% of the patients met remission criteria at >=2 visits.
      Agreement between criteria definitions was good, as assessed by kappa statistics
      and Jaccard coefficients. Among patients in remission, the probability of a
      remission lasting 2 years was 6.0-14.1%. Among all patients, the probability of a
      remission lasting 2 years was <3%. Remission status and examination results for
      each patient varied substantially among physicians, as determined by multilevel
      analyses. CONCLUSION: Cross-sectional remission occurred in 5.0-10.1% of the
      patients in these cohorts, with cumulative remission being 2-3 times greater;
      however, long-term remission was rare. Problems with reliability and agreement
      limit the usefulness of these criteria in the individual patient. However, the
      criteria can be an effective method for measuring clinical status and treatment
      effect in groups of patients in the community.

PMID- 21739424
TI  - The association between hip morphology parameters and nineteen-year risk of end
      stage osteoarthritis of the hip: a nested case-control study.
AB  - OBJECTIVE: Subtle deformities of the hip joint are implicated in the etiology of
      osteoarthritis (OA) of the hip. Parameters that quantify these deformities may
      aid understanding of these associations. We undertook this study to examine
      relationships between such parameters and the 19-year risk of total hip
      arthroplasty (THA) for end-stage OA. METHODS: A new software program designed for
      measuring morphologic parameters around the hip was developed and validated in a
      reliability study. THA was the outcome measure for end-stage OA. A nested case
      control study was used with individuals from a cohort of 1,003 women who were
      recruited at year 1 in 1989 and followed up to year 20 (the Chingford Study). All
      hips with THA by year 20 and 243 randomly selected control hips were studied.
      Pelvis radiographs obtained at year 2 were analyzed for variations in hip
      morphology. Measurements were compared between the THA case group and the control
      group. RESULTS: Patients with THA had a higher prevalence of cam deformity than
      did their respective controls (median alpha angle 62.4 degrees  versus 45.8
      degrees  [P = 0.001]; mean modified triangular index height 28.5 mm versus 26.9
      mm [P = 0.001]) as well as a higher prevalence of acetabular dysplasia (mean
      lateral center edge angle 29.5 degrees  versus 34.3 degrees  [P = 0.001]; median
      extrusion index 0.25 versus 0.185 [P = 0.009]). Logistic regression analyses
      clustering by subject and adjusting for radiographic hip OA at year 2 showed that
      these morphologic parameters were still significantly associated with THA by year
      20. The alpha angle and lateral center edge angle predicted the risk of THA
      independently when included in the same model. CONCLUSION: This investigation
      describes measurements that predict the risk of THA for end-stage OA by year 20,
      independently of the presence of radiographic hip OA at year 2. These
      measurements can be made on an anteroposterior pelvis radiograph, which is an
      inexpensive and commonly used clinical method of investigation.

PMID- 21739425
TI  - Interactions of human monoclonal and polyclonal antiphospholipid antibodies with
      serine proteases involved in hemostasis.
AB  - OBJECTIVE: To characterize the interaction between procoagulant and/or
      anticoagulant serine proteases and human monoclonal IgG antiphospholipid
      antibodies (aPL) and polyclonal IgG derived from patients with the
      antiphospholipid syndrome (APS). METHODS: Five human monoclonal IgG with small
      differences in their sequences were tested for binding to protein C, activated
      protein C, plasmin, factor VIIa (FVIIa), FIX, FIXa, and FXII. Serum levels of
      antithrombin and anti-activated protein C were compared in 32 patients with APS,
      29 patients with systemic lupus erythematosus (SLE), and 22 healthy controls.
      Purified polyclonal IgG derived from APS patients with elevated levels of serum
      antithrombin antibodies was also tested for its functional effects on thrombin
      and antithrombin activity. RESULTS: Studies of monoclonal antibodies showed that
      sequence changes in human aPL are important in determining their ability to bind
      procoagulant and anticoagulant/fibrinolytic serine proteases. Mean IgG
      antithrombin levels were significantly elevated in patients with APS and in SLE
      patients with aPL but no APS (SLE/aPL+) compared to healthy controls, but anti
      activated protein C levels were not increased in these patients. Moreover, IgG
      purified from patients with APS displayed higher avidity for thrombin and
      significantly inhibited antithrombin inactivation of thrombin compared with IgG
      from SLE/aPL+ patients. CONCLUSION: High-avidity antithrombin antibodies, which
      prevent antithrombin inactivation of thrombin, distinguish patients with APS from
      SLE/aPL+ patients, and thus may contribute to the pathogenesis of vascular
      thrombosis in APS.

PMID- 21739426
TI  - Resistin and insulin/insulin-like growth factor signaling in rheumatoid
      arthritis.
AB  - OBJECTIVE: Human resistin has proinflammatory properties that activate NF-kappaB
      dependent pathways, whereas its murine counterpart is associated with insulin
      resistance. The aim of this study was to examine potential cross-talk between
      resistin and insulin/insulin-like growth factor (IGF) signaling in rheumatoid
      arthritis (RA). METHODS: Levels of IGF-1, IGF binding protein 3, and resistin
      were measured in the blood and synovial fluid of 60 patients with RA and 39
      healthy control subjects. Human RA synovium was implanted subcutaneously into
      SCID mice, and the mice were treated with resistin-targeting small interfering
      RNA. Primary synovial fibroblasts from patients with RA, as well as those from
      patients with osteoarthritis, and the human fibroblast cell line MRC-5 were
      stimulated with resistin. Changes in the IGF-1 receptor (IGF-1R) signaling
      pathway were evaluated using histologic analysis, immunohistochemistry, and
      reverse transcription-polymerase chain reaction. RESULTS: Resistin and IGF-1R
      showed different expression profiles in RA synovia. Low levels of IGF-1 in RA
      synovial fluid were associated with systemic inflammation and inversely related
      to the levels of resistin. Stimulation of synovial fibroblasts with resistin
      induced phosphorylation of IGF-1R to a degree similar to that with insulin, and
      also induced phosphorylation of transcription factor Akt. This was followed by
      gene expression of GLUT1, IRS1, GSK3B, and the Akt inhibitors PTPN and PTEN.
      Abrogation of resistin expression in vivo reduced the expression of IGF-1R, the
      phosphorylation of Akt, and the expression of PTPN and PTEN messenger RNA in RA
      synovium implanted into SCID mice. CONCLUSION: Resistin utilizes the IGF-1R
      pathway in RA synovia. Abrogation of resistin synthesis in the RA synovium in
      vivo leads to reductions in the expression of IGF-1R and level of phosphorylation
      of Akt.

PMID- 21739427
TI  - Long-term outcome of isolated limb perfusion with tumour necrosis factor-alpha
      for patients with melanoma in-transit metastases.
AB  - BACKGROUND: The use of tumour necrosis factor (TNF) alpha in isolated limb
      perfusion (ILP) for in-transit melanoma metastasis is not uniformly accepted.
      This article reports the long-term results of adding TNF-alpha to standard
      melphalan-based ILP (TM-ILP) for treatment of melanoma in-transit metastases.
      METHODS: Data for patients treated between 1991 and 2005 were retrieved from a
      prospectively maintained database. Hyperthermic ILP was performed with 1-4 mg TNF
      alpha. With a median potential follow-up of 13 years, response rates, time to
      local progression and disease-specific survival were analysed in relation to
      standard baseline factors. RESULTS: Some 118 TM-ILPs were analysed in 105
      patients, 54 for stage IIIA, 50 for stage IIIAB and 14 for stage IV disease. The
      overall response rate was 93.2 per cent; the response was complete in 67.8 per
      cent and partial in 25.4 per cent. The response rate was significantly influenced
      by stage of disease (IIIA versus IIIAB; P = 0.006). The complete response was
      maintained until the end of follow-up in 35 patients (33.3 per cent), and local
      control was achieved with one additional intervention in 12 others (11.4 per
      cent). Local progression occurred after 66 ILPs (55.9 per cent). Number of in
      transit metastases (P = 0.008) and complete response after ILP (P < 0.001) were
      strong prognostic factors for time to local progression. The 5-year disease
      specific survival rate was 27.3 per cent; survival was positively influenced by
      age, stage of disease, previous ILP and complete response after ILP. CONCLUSION:
      ILP with TNF-alpha may obtain long-term local control in selected patients with
      in-transit metastases from melanoma.

PMID- 21739428
TI  - Human Langerhans cells capture measles virus through Langerin and present viral
      antigens to CD4+ T cells but are incapable of cross-presentation.
AB  - Langerhans cells (LCs) are a subset of DCs that reside in the upper respiratory
      tract and are ideally suited to sense respiratory virus infections. Measles virus
      (MV) is a highly infectious lymphotropic and myelotropic virus that enters the
      host via the respiratory tract. Here, we show that human primary LCs are capable
      of capturing MV through the C-type lectin Langerin. Both immature and mature LCs
      presented MV-derived antigens in the context of HLA class II to MV-specific
      CD4(+)  T cells. Immature LCs were not susceptible to productive infection by MV
      and did not present endogenous viral antigens in the context of HLA class I. In
      contrast, mature LCs could be infected by MV and presented de novo synthesized
      viral antigens to MV-specific CD8(+)  T cells. Notably, neither immature nor
      mature LCs were able to cross-present exogenous UV-inactivated MV or MV-infected
      apoptotic cells. The lack of direct infection of immature LCs, and the inability
      of both immature and mature LCs to cross-present MV antigens, suggest that human
      LCs may not be directly involved in priming MV-specific CD8(+)  T cells. Immune
      activation of LCs seems a prerequisite for MV infection of LCs and subsequent
      CD8(+)  T-cell priming via the endogenous antigen presentation pathway.

PMID- 21739429
TI  - The central role of CD30L/CD30 interactions in allergic rhinitis pathogenesis in
      mice.
AB  - CD30 ligand (CD30L) plays an important role in the amplification and/or
      activation of effector CD4(+)  T cells, irrespective of Th cell subset. To
      examine the role of CD30L in allergic rhinitis, we evaluated an OVA model of
      allergic rhinitis in CD30L knock out (KO) mice on a BALB/c background sensitized
      with OVA. Symptoms of allergic rhinitis such as eosinophil infiltration into the
      nasal mucosa were drastically diminished in OVA-sensitized CD30L KO mice
      following intranasal challenge with OVA. The levels of OVA-specific IgE in the
      sera and the Th2 response in nasopharynx-associated lymphoid tissues and cervical
      LNs of CD30L KO mice were significantly lower than those of WT mice following
      intranasal challenge with OVA. Intranasal administration of CD30-Ig during the
      effector phase with OVA significantly prevented the development of allergic
      rhinitis in WT mice. These results suggest that CD30L plays an important role in
      allergic rhinitis and that the inhibition of CD30L/CD30 signaling might be useful
      as a novel biological therapy for allergic rhinitis.

PMID- 21739430
TI  - The effect of pregnancy on the uterine NK cell KIR repertoire.
AB  - The major leukocyte population in the decidua during the first trimester of
      pregnancy consists of NK cells that express receptors capable of recognizing MHC
      class I molecules expressed by placental trophoblast. These include members of
      the killer immunoglobulin-like receptor (KIR) family, the two-domain KIR (KIR2D),
      which recognize HLA-C. Interactions between decidual NK (dNK) cell KIR2D and
      placental HLA-C contribute to the success of pregnancy and dNK cells express
      KIR2D at higher frequency than peripheral NK (pNK) cells. Thus, they are biased
      toward recognizing HLA-C. In order to investigate when this unusual KIR
      repertoire appears, we compared the phenotype of NK cells isolated from non
      pregnant (endometrium) and pregnant (decidua) human uterine mucosa. Endometrial
      NK (eNK) cells did not express KIR2D at a higher level than matched pNK cells, so
      the bias toward HLA-C recognition occurs as a response to pregnancy. Furthermore,
      HLA-C expression was upregulated on uterine stromal cells as the mucosa
      transformed from endometrium to decidua at the onset of pregnancy. As uterine NK
      (uNK) cells can mature from NK precursors and acquire KIR expression in utero,
      the pregnancy-specific bias of uNK cells toward HLA-C recognition could arise as
      developing uNK cells interact with uterine stromal cells, which express higher
      levels of HLA-C during pregnancy.

PMID- 21739431
TI  - Autonomous and extrinsic regulation of thymopoiesis in human immune system (HIS)
      mice.
AB  - Human Immune System (HIS) mice represent a novel biotechnology platform to
      dissect human haematopoiesis and immune responses. However, the limited human T
      cell development that is observed in HIS mice restricts its utility for these
      applications. Here, we address whether reduced thymopoiesis in HIS mice reflects
      an autonomous defect in T-cell precursors and/or a defect in the murine thymic
      niche. Human thymocyte precursors seed the mouse thymus and their reciprocal
      interactions with murine thymic epithelial cells (TECs) led to both T-cell and
      TEC maturation. The human thymocyte subsets observed in HIS mice demonstrated
      survival, proliferative and phenotypic characteristics of their normal human
      counterparts, suggesting that the intrinsic developmental program of human
      thymocytes unfolds normally in this xenograft setting. We observed that exogenous
      administration of human IL-15/IL-15Ralpha agonistic complexes induced the
      survival, proliferation and absolute numbers of immature human thymocyte subsets,
      without any obvious effect on cell-surface phenotype or TCR Vbeta usage amongst
      the newly selected mature single-positive (SP) thymocytes. Finally, when IL-15
      was administered early after stem cell transplantation, we noted accelerated
      thymopoiesis resulting in the more rapid appearance of peripheral naive T cells.
      Our results highlight the functional capacity of murine thymic stroma cells in
      promoting human thymopoiesis in HIS mice but suggest that the "cross-talk"
      between murine thymic stroma and human haematopoietic precursors may be
      suboptimal. As IL-15 immunotherapy promotes early thymopoiesis, this novel
      approach could be used to reduce the period of T-cell immunodeficiency in the
      post-transplant clinical setting.

PMID- 21739432
TI  - GM1 expression in caco-2 cells: characterisation of a fundamental passage
      dependent transformation of a cell line.
AB  - Caco-2 cells, which are known to spontaneously differentiate in cell culture,
      adopt typical epithelial characteristics and are widely used as a model to study
      cellular uptake, transport and metabolism processes. However, groups of flat and
      undifferentiated cells have been observed amid differentiating Caco-2 cell
      monolayers. In this study, we isolated and characterised these morphologically
      distinct, flat and island-forming Caco-2 cells. We visualised the
      undifferentiated cell islands with the aid of optical and electron microscopy and
      identified mono-sialo-ganglioside one (GM1) as their unique marker. Furthermore,
      two distinct subpopulations of morphology and GM1 expression were dilution cloned
      (Caco-2(GM1-) and Caco-2(GM1+) ), leading to the first documented Caco-2 clone
      that does not show differentiation characteristics. Caco-2(GM1+) cells were flat,
      non-polarising with extremely low transepithelial electrical resistance (TEER),
      whereas Caco-2(GM1-) cells showed typical epithelial features and high TEER.
      Importantly, the proportion of Caco-2(GM1+) cells in a culture increased with
      passage number and eventually dominated the cell culture. The novel GM1 passage
      dependent cell transformation described here shows that careful monitoring is
      required when performing in vitro cell studies. Therefore, to guarantee
      consistent and valid experimental data, GM1 expression and the loss of
      differentiation characteristics should be carefully monitored and the use of
      fresh cultures should be standard practice.

PMID- 21739433
TI  - Sinonasal malignancies in children: a 10-year, single-institutional review.
AB  - OBJECTIVES: Sinonasal malignancies in children are rare, histologically diverse
      tumors that present diagnostic and management challenges. The purpose of this
      study is to review the experience of a single cancer center in the management of
      pediatric sinonasal malignancies. STUDY DESIGN: Retrospective review. METHODS:
      Retrospective chart review. RESULTS: Forty-four patients were identified. The
      median age was 12 years (range: 2-17), 54% were female, and the maxillary sinus
      was the most common primary site. Facial swelling and pain were the most common
      presenting complaints. Thirty-four patients (76%) in this series had paranasal
      sinus sarcomas, three patients had esthesioneuroblastomas, and eight patients had
      carcinomas. The 5-year overall survival, disease-specific survival, and
      recurrence rate for the entire group was 71%, 81%, and 43%, respectively.
      CONCLUSIONS: Pediatric sinonasal malignancies are rare, locally aggressive tumors
      associated with nonspecific signs and symptoms. Multimodality treatment can
      result in 5-year overall and disease-specific survival rates of over 70%. A
      multidisciplinary team approach is essential to optimize outcomes and limit the
      morbidity of treatment.

PMID- 21739434
TI  - Investigation of phosphoprotein signatures of archived prostate cancer tissue
      specimens via proteomic analysis.
AB  - Early detection of prostate cancer and determination of its aggressiveness are
      critical factors that influence treatment outcomes. To aid in the clinical
      decision making, novel biomarkers are being sought. Direct, global-scale
      examination of primary human specimens provides the most relevant picture of the
      tumor machinery and its perturbations, and this information is highly significant
      in the context of biomarker discovery. In the pilot study reported here, we
      focused on mapping of the phosphoproteome in human prostate cancer specimens
      obtained from a tissue repository. A gel-free proteomic strategy included whole
      proteome digestion, phosphopeptide enrichment with immobilized metal ion affinity
      chromatography (IMAC), and phosphoprotein identification via LC-MS/MS and
      database searches. We applied this strategy to obtain phosphoprotein signatures
      from a set of five specimens. Phosphoproteins were characterized from each
      specimen. The phosphoprotein panels included 16-23 phosphoproteins that
      encompassed 18-30 phosphorylation sites. Some of proteins/sites were
      characterized in multiple specimens, whereas the majority of sites were found in
      single specimens. The characterized panels include caldesmone, desmin, HSP beta
      1, synaptopodin-2, filamin-C, tensin-1, and others. In summary, the study showed
      that cancer-relevant phosphoproteins can be characterized directly from archived
      prostate tumor specimens, establishing the groundwork for further biomarker
      discovery.

PMID- 21739435
TI  - Role of endoscopic sonography in the diagnosis of a fish bone perforation of the
      gastric wall resulting in a submucosal pseudotumor.
AB  - We report the case of a 72-year-old woman with a fish bone-induced granulation
      tissue in the gastric wall that was initially diagnosed as a submucosal tumor by
      panendoscopy. High-frequency endoscopic ultrasonography identified the linear
      calcified fish bone embedded in a heterogeneous mass.

PMID- 21739436
TI  - Mucocele of the vermiform appendix misdiagnosed as an adnexal mass on
      transvaginal sonography.
AB  - Mucocele of the vermiform appendix is a rare entity that may mimic a right-sided
      adnexal mass. We describe a case of appendiceal mucocele in a 78-year-old woman
      that was initially misdiagnosed as a potentially malignant right ovarian tumor
      and briefly review the literature on sonographic features of this entity. It is
      important to improve preoperative diagnosis so as to prevent rupture of mucocele
      at surgery, which may lead to pseudomyxoma peritonei, and also to seek
      intraoperatively for the presence of synchronous colorectal neoplasms.

PMID- 21739437
TI  - A cluster of patients with recombinant B/F HIV-1 infection: epidemiological,
      clinical, and virological aspects.
AB  - Migratory processes have caused changes in human immunodeficiency virus (HIV)
      epidemiology and non-B subtypes are now playing an increasing role. In a cohort
      of 553 HIV-infected outpatients tested to identify non-B isolates, the largest
      group consisted of 13 subjects with a recombinant B/F form (prevalence 2.4%).
      Sequencing and phylogenetic analyses described a B/F recombinant clade with
      anomalous breakpoints that did not allow it to be classified as CRF12_BF. Viral
      load was not quantified efficiently because of a mismatch in the primers and
      probes used by commercial assays. An assessment of the clinical management, and
      epidemiological, immunological, and virological characteristics of these
      patients, who were receiving non-nucleoside reverse transcriptase inhibitor
      (NNRTI)- or protease inhibitor (PI)-based regimens, showed that the immunological
      and virological mismatch delayed the start of treatment by a mean of 6.8 months.
      Therapy was started in nine patients. Both NNRTI- and PI-based regimens led to
      full virological suppression after a mean 36 weeks of treatment; the PI-based
      regimens proved to be more effective in terms of immunological recovery (1,341
      vs. 544 CD4+ cells/mm(3) ). The spread of non-B subtypes is increasing throughout
      the world but their response to treatment is still unclear. PIs and NNRTIs are
      effective but further tests are needed to allow the more efficient recognition of
      these viral strains and establish how they should be treated.

PMID- 21739438
TI  - Greater diversity of HIV DNA variants in the rectum compared to variants in the
      blood in patients without HAART.
AB  - The gut-associated lymphoid tissue represents the largest reservoir of HIV-1.
      Improving knowledge of this reservoir by studying the diversity of viral
      population is a key step towards understanding the pathogenesis and dynamics of
      HIV. Obtaining samples is difficult and little information is available on gut
      viral quasispecies during the course of infection in humans. The aim of this
      study was to characterize rectal viral strains and their diversity and to
      investigate the relationships between the rectal tissue reservoir and viral
      variants in the blood. Phylogenetic analyses were performed on the env sequences
      for rectal HIV DNA, blood HIV DNA, and HIV RNA clones, with maximum-likelihood
      and neighbor-joining methods on seven patients. Genetic diversity was assessed.
      Higher diversity of HIV DNA clones was noted in the rectum compared to blood in
      four out of five patients without HAART. Viral diversity was present in the
      rectum from time of the primary infection. Similar degrees of diversity were
      observed in the rectum and blood during HAART. Rectal and blood HIV variants were
      interspersed partially or totally in the seven patients. A certain number of
      rectal HIV DNA clones were clustered together in six patients. These results
      suggest that variants in the rectum were more heterogeneous than variants in the
      blood from patients without HAART, probably because the activated milieu of gut
      associated lymphoid tissue may provide an improved environment for viral
      replication, and indicate exchange of viral populations between blood and rectal
      tissues, reflecting the dynamics of HIV during course of infection.

PMID- 21739439
TI  - Resistance to antiretroviral drugs in newly diagnosed, young treatment-naive HIV
      positive pregnant women in the province of KwaZulu-Natal, South Africa.
AB  - In 2004, KwaZulu-Natal initiated one of the world's largest HIV/AIDS treatment
      programs. Studies in South Africa have shown that patients on antiretroviral
      therapy (ART) develop rapidly and transmit drug resistant mutations. Since
      resistance testing is not widely available in Kwazulu-Natal, the Department of
      Health conducted the first HIV drug resistance (HIVDR) threshold survey in 2005,
      which did not identify any mutations associated with HIVDR. The objective of this
      study was to conduct a follow-up threshold survey to update the information on
      HIVDR. This study was conducted in 2009 in five antenatal care sites in Kwazulu
      Natal using the HIVDR threshold survey method developed by WHO. Two hundred and
      thirteen newly-diagnosed HIV positive, drug-naive primigravidae, less than 22
      years of age were included in the survey. Of the 82 HIV positive specimens, 17
      had insufficient volume for genotyping and, of the remaining 65, 47 were
      genotyped sequentially. Drug resistance was identified by sequencing the HIV-1
      pol gene, using the ViroSeq(r) HIV-1 genotyping system v2.0. Of the 47 samples
      that were genotyped, only one presented with a K103N mutation, which equates to a
      prevalence of transmitted HIVDR of <5%. The low prevalence of transmitted HIVDR
      is in keeping with statistical models of the early stages of ART rollout. As ART
      coverage is increasing continuously, there is a need to ensure that vigilance of
      HIVDR continues so that the emergence and spread of HIVDR is minimized.

PMID- 21739440
TI  - Hepatitis B surface antigen confirmatory testing for diagnosis of hepatitis B
      virus infection in Taiwan.
AB  - This study aimed to examine the application of hepatitis B surface antigen
      (HBsAg) confirmatory testing when diagnosing hepatitis B infection among young
      persons in Taiwan with a low prevalence rate of hepatitis B infection. HBsAg
      status, the presence of antibodies against HBsAg (anti-HBs), and the presence of
      antibodies against hepatitis B core antigen (anti-HBc) were compared among 403
      graduate students (mean age 22.8 +/- 0.7 years) and 1,745 undergraduate students
      (18.6 +/- 1.0 years) from one university, and 367 adult subjects (41.1 +/- 15.8
      years) in 2008. Any HBsAg-positive subjects were tested with an HBsAg
      confirmatory test. Chi-square tests for trend and predictive values of positivity
      (PVP) when using HBsAg-positive only for determining confirmed cases of hepatitis
      B infection were compared across the three cohorts. The prevalence of HBsAg
      positivity among subjects decreased from 16.3% in the adults to 5.2% in the
      graduate students and then to 2.8% for the undergraduate students (P = 0.0007).
      The PVP of HBsAg testing when determining cases of hepatitis B decreased from
      0.97 for the adults to 0.81 for the graduate students and then to 0.56 for the
      undergraduate students (P < 0.0001). Thus, a significant decrease in the true
      positive rate of HBsAg among the students born after the introduction of
      hepatitis B vaccination was observed only when HBsAg testing was applied.
      Additional neutralization tests may therefore become mandatory for persons with a
      positive HBsAg test result who were born after the commencement of the universal
      neonatal hepatitis B vaccination program in Taiwan.

PMID- 21739441
TI  - Assessment of dried blood spot samples as a simple method for detection of
      hepatitis B virus markers.
AB  - Detection of hepatitis B virus (HBV) serological markers in dried blood spot
      (DBS) samples by enzyme immunoassay (ELISA) has not yet been fully optimized. In
      this study, the ability to detect three HBV markers (HBsAg, anti-HBc, and anti
      HBs) was evaluated in DBS samples using a modified commercial ELISA. Matched
      serum and DBS samples were obtained from individuals with or without a past
      history of HBV infection. Sera samples were tested according to the
      manufacturer's instructions, but for DBS testing, paper diameters, elution
      buffer, volume of input sample, and cut-off values were evaluated to optimize the
      assay. Stability studies were done on DBS stored at for up to 180 days at
      different temperatures. The absorbance values that yielded the maximum
      sensitivity and specificity were determined based on the area under the ROC curve
      (AUROC) and chosen as the cut-off value. Using this parameter, sensitivity was
      90.5%, 97.6%, and 78% for anti-HBc, HBsAg, anti-HBs assays, respectively.
      Specificity was 92.6%, 96.7%, and 97.3% for anti-HBc, HBsAg, and anti-HBs assays,
      respectively. HBV markers could be detected in DBS samples until 63 days after
      sample collection at most temperatures, but storage at -20 degrees C yielded more
      consistent results. These results indicate that modified ELISA can be used to
      detect HBV markers in DBS samples, particularly if the samples are stored
      appropriately.

PMID- 21739442
TI  - Phylogenetic analysis of hepatitis B virus genotype F complete genome sequences
      from Chilean patients with chronic infection.
AB  - Molecular epidemiological data concerning the hepatitis B virus (HBV) in Chile
      are not known completely. Since the HBV genotype F is the most prevalent in the
      country, the goal of this study was to obtain full HBV genome sequences from
      patients infected chronically in order to determine their subgenotypes and the
      occurrence of resistance-associated mutations. Twenty-one serum samples from
      antiviral drug-naive patients with chronic hepatitis B were subjected to full
      length PCR amplification, and both strands of the whole genomes were fully
      sequenced. Phylogenetic analyses were performed along with reference sequences
      available from GenBank (n = 290). The sequences were aligned using Clustal X and
      edited in the SE-AL software. Bayesian phylogenetic analyses were conducted by
      Markov Chain Monte Carlo simulations (MCMC) for 10 million generations in order
      to obtain the substitution tree using BEAST. The sequences were also analyzed for
      the presence of primary drug resistance mutations using CodonCode Aligner
      Software. The phylogenetic analyses indicated that all sequences were found to be
      the HBV subgenotype F1b, clustered into four different groups, suggesting that
      diverse lineages of this subgenotype may be circulating within this population of
      Chilean patients.

PMID- 21739443
TI  - Development of chronic hepatitis B virus infection in hepatitis B surface antigen
      negative HIV/HBV co-infected adults: a rare opportunistic illness.
AB  - Changes in serologic status in human immunodeficiency virus (HIV)/hepatitis B
      virus (HBV) co-infected individuals with either isolated anti-HBc or resolved HBV
      infection have been reported, but the frequency of clinically meaningful long
      term serologic changes is not well-defined. This study therefore, examined
      longitudinal serologic status for hepatitis B surface antigen (HBsAg)-negative
      HIV/HBV co-infected participants in a large cohort. Among 5,222 cohort
      participants, 347 (7%) were initially isolated anti-HBc positive, and 1,073 (21%)
      had resolved HBV infection (concurrently reactive for anti-HBc and anti-HBs).
      Thirty-three (10%) of the 347 participants with isolated anti-HBc were later
      positive for HBsAg at least once, compared with 3 (0.3%) of those with resolved
      HBV (P < 0.001). A total of 14 participants became persistently positive for
      HBsAg and were thus classified as having late-onset chronic HBV infection at a
      median of 3.7 years after initial HBV diagnosis. For those initially with HBsAg
      negative HIV/HBV co-infection, the rate of late-onset chronic HBV infection was
      1.39/1,000 person-years. Those with late-onset chronic HBV infection experienced
      significant decreases in CD4 cell counts (P = 0.002) with a mean of 132 cells/ul
      at the time of late-onset chronic HBV infection, but no factor distinguished
      those who were positive for HBsAg only once from those that developed late-onset
      chronic HBV infection. Over a median of 2.9 years following late-onset chronic
      HBV infection, 3 of 14 subsequently lost HBsAg. The occurrence of late-onset
      chronic HBV infection in HBsAg negative HIV/HBV co-infected adults appears to be
      one important, albeit rare, clinical event seen almost exclusively in those with
      isolated anti-HBc and low CD4 cell count.

PMID- 21739444
TI  - Hepatitis B virus genotype B with G1896A and A1762T/G1764A mutations is
      associated with hepatitis B related acute-on-chronic liver failure.
AB  - The existence of statistical associations between hepatitis B-related acute-on
      chronic liver failure and both hepatitis B virus (HBV) genotype and mutations in
      the basal core promoter (BCP) and precore (PC) regions needs to be confirmed. A
      total of 322 patients with a chronic HBV infection, including 77 with hepatitis B
      related acute-on-chronic liver failure, 109 with hepatocellular carcinoma (HCC)
      and 136 with chronic hepatitis B (CHB) were enrolled. The HBV genotype and the
      presence of mutations in the BCP/PC regions were determined by direct sequencing,
      and the frequencies were compared in the three patient groups. Overall, 198/322
      (61.5%) were infected with genotype B and 124/322 (38.5%) with genotype C.
      Genotype B was significantly more frequent in patients with acute-on-chronic
      liver failure than CHB (92.2% vs. 60.3%, P < 0.001). As a contrast, genotype C
      was more common in patients with HCC than CHB (58.7% vs. 39.7%, P = 0.003). In
      genotype B patients, the A1762T/G1764A, A1846T, and G1896A mutations were
      significantly more prevalent in patients with acute-on-chronic liver failure than
      CHB (50.7% vs. 28.0%, P = 0.004; 59.2% vs. 34.1%, P = 0.002; 69.0% vs. 41.5%, P =
      0.001, respectively). In multivariate analysis, the risk factors for acute-on
      chronic liver failure were genotype B, A1762T/G1764A, and G1896A. In conclusion,
      CHB patients with genotype B, G1896A, and A1762T/G1764A had a higher tendency to
      develop liver failure than patients with genotype C. Therefore, HBV genotyping
      and detecting G1896A and A1762T/G1764A mutations might have important clinical
      implications as predictive risk factors for hepatitis B-related acute-on-chronic
      liver failure.

PMID- 21739445
TI  - Hepatitis B virus genotype G: prevalence and impact in patients co-infected with
      human immunodeficiency virus.
AB  - Relatively little is known about the role of hepatitis B virus (HBV) genotype G
      (HBV/G) in patients co-infected with human immunodeficiency virus (HIV) and HBV.
      This study examined the prevalence and association of HBV/G to liver fibrosis in
      co-infected patients. HBV genotypes were determined by direct sequencing of the
      HBV surface gene or Trugene(r) HBV 1.0 assay in 133 patients infected with
      HIV/HBV. Quantitative testing of HBV-DNA, HBeAg, and anti-HBe were performed
      using the Versant(r) HBV 3.0 (for DNA) and the ADVIA(r)Centaur assay. The non
      invasive biomarkers Fib-4 and APRI were used to assess fibrosis stage. Genotype A
      was present in 103/133 (77%) of the cohort, genotype G in 18/133 (14%) with
      genotypes D in 8/133, (6%), F 2/133 (1.5%), and H 2/133 (1.5%). Genotype G was
      associated with hepatitis B e antigen-positivity and high HBV-DNA levels.
      Additionally, HBV/G (OR 8.25, 95% CI 2.3-29.6, P = 0.0012) was associated with
      advanced fibrosis score using Fib-4, whereas, being black was not (OR 0.19, 95%
      CI 0.05-0.07, P = 0.01). HBV/G in this population exhibited a different phenotype
      than expected for pure G genotypes raising the question of recombination or mixed
      infections. The frequent finding of HBV/G in co-infected patients and its
      association with more advanced fibrosis, suggests that this genotype leads to
      more rapid liver disease progression. Further studies are needed to understand
      why this genotype occurs more frequently and what impact it has on liver disease
      progression in patients with HBV/HIV.

PMID- 21739446
TI  - Antiviral combination therapy with peginterferon and ribavirin does not induce a
      therapeutically resistant mutation in the HCV core region regardless of genetic
      polymorphism near the IL28B gene.
AB  - An association has been reported between genetic polymorphism near IL28B gene and
      the prevalence of mutation of hepatitis C virus (HCV) core region residue 70,
      both of which have been associated with a lack of virologic response to antiviral
      combination therapy with peginterferon (PEG-IFN) and ribavirin. This study
      investigated whether PEG-IFN/ribavirin combination therapy induces amino acid
      (AA) mutation at residue 70 of HCV and whether genetic polymorphism near IL28B
      gene affects it. AA substitutions at residue 70 of the HCV core region were
      measured and compared before and after combination therapy in 65 non-responders
      and 88 relapsers to the combination therapy. In three patients in whom both wild
      type AA (arginine) and mutant-type AA (glutamine or histidine) were detected at
      residue 70 before treatment, only mutant-type AA was identified after treatment.
      In two patients who had wild-type AA solely before treatment, both wild-type and
      mutant-type AAs were identified at residue 70 after treatment. In five patients,
      in whom the AA had changed at residue 70 between before and after treatment, four
      patients carried the TT genotype at a polymorphic locus (rs8099917) near the
      IL28B gene and one carried the TG/GG genotype. No difference was found in the
      prevalence of this change of AA at residue 70 between the TT and the TG/GG
      genotype. Antiviral combination therapy with PEG-IFN and ribavirin does not
      appear to induce mutation of HCV core region residue 70 regardless of genetic
      polymorphism near the IL28B gene in Japanese patients infected with HCV genotype
      1b.

PMID- 21739447
TI  - Molecular analysis of hepatitis C virus infection in Bulgarian injecting drug
      users.
AB  - Intravenous drug users constitute a group at risk for hepatitis C virus (HCV)
      infection. Today, no data are available on the molecular epidemiology of HCV in
      Bulgaria despite the fact that in recent years the incidence of acute hepatitis C
      infection among Bulgarian intravenous drug users increased sixfold and about 2/3
      of them developed a chronic infection. The aim of this study was to determine the
      circulation of hepatitis C genotypes among drug users and to study the evolution
      and transmission history of the virus by molecular clock and Bayesian methods,
      respectively. Sequencing of NS5B gene showed that the genotype 3a was the most
      prevalent type among intravenous drug users. In the Bayesian tree, the 3a
      subtypes grouped in one main clade with one small cluster well statistically
      supported. The root of the tree was dated back to the year 1836, and the main
      clade from Bulgaria was dated 1960. The effective number of infections remained
      constant until about years 1950s, growing exponentially from the 1960s to the
      1990s, reaching a plateau in the years 2000. The not significant intermixing with
      isolates from other countries may suggest a segregated circulation of the
      epidemic between 1940s and 1980s. The plateau reached by the epidemic in the
      early 2000s may indicate the partial success of the new preventive policies
      adopted in Bulgaria.

PMID- 21739448
TI  - Molecular determinants of disease in coxsackievirus B1 murine infection.
AB  - To understand better how different genomic regions may confer pathogenicity for
      the coxsackievirus B (CVB), two intratypic CVB1 variants, and a number of
      recombinant viruses were studied. Sequencing analysis showed 23 nucleotide
      changes between the parental non-pathogenic CVB1N and the pathogenic CVB1Nm.
      Mutations present in CVB1Nm were more conserved than those in CVB1N when compared
      to other CVB sequences. Inoculation in C3H/HeJ mice showed that the P1 region is
      critical for pathogenicity in murine pancreas and heart. The molecular
      determinants of disease for these organs partially overlap. Several P1 region
      amino acid differences appear to be located in the decay-accelerating factor
      (DAF) footprint CVBs. CVB1N and CVB1Nm interacted with human CAR, but only CVB1N
      seemed to interact with human DAF, as determined using soluble receptors in a
      plaque-reduction assay. However, the murine homolog Daf-1 did not interact with
      any virus assessed by hemagglutination. The results of this study suggest that an
      unknown receptor interaction with the virus play an important role in the
      pathogenicity of CVB1Nm. Further in vivo studies may clarify this issue.

PMID- 21739449
TI  - Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus
      reactivation, and varicella zoster virus encephalitis during treatment of
      medulloblastoma.
AB  - The case of a 14-year-old girl who developed Epstein-Barr virus-related
      lymphoproliferative disorder, cytomegalovirus reactivation, and Varicella zoster
      virus encephalitis during treatment for medulloblastoma is described. The patient
      was diagnosed with a cerebral medulloblastoma and treated with systemic
      chemotherapy, intrathecal chemotherapy, and radiotherapy. Six months later, she
      developed persistent low-grade fever, abdominal pain, and vomiting. Several
      mucosal or ulcerated lesions of the stomach and colon were found on fiberscopy.
      The infiltrating cells were positive for CD20 and EBER1, and the diagnosis of
      lymphoproliferative disorder was made. CMV antigen was found in the peripheral
      lymphocytes at that time. At the same time, it was noted that the patient's
      language was inappropriate for her age, and a facial and abdominal rash, as well
      as a right facial palsy, had developed. She was then diagnosed as having VZV
      encephalitis, because VZV was detected in the CSF. She was treated subsequently
      with acyclovir and oral steroid, and the VZV encephalitis resolved. The
      lymphoproliferative disorder improved gradually with rituximab, ganciclovir, and
      total nutritional support. At the time of the development of the
      lymphoproliferative disorder and VZV encephalitis, the patient had severe
      lymphopenia and this may have caused these rare phenomena in a non-transplant
      setting.

PMID- 21739450
TI  - Epstein-Barr virus, B cell lymphoproliferative disease, and SCID mice: modeling T
      cell immunotherapy in vivo.
AB  - Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease
      (PTLD) arises in up to 10% of organ transplant recipients and is fatal in ~50% of
      cases. PTLD can be modeled in SCID mice using EBV+ve human B lymphoblastoid cell
      lines (BLCLs), and the current study investigated intraperitoneal (ip)
      inoculation of such animals in experiments which assessed the effect of EBV
      specific cytotoxic T lymphocytes (CTLs) and cytokines on PTLD growth. Ip transfer
      of one dose of autologous CTLs, or CD8-enriched T cells, into ip BLCL-inoculated
      animals significantly delayed tumor development (P = 0.001) and prevented tumor
      formation in a significant proportion (40%) of mice (P = 0.001). A combination of
      interleukin (IL)2, 7, and 15 conditioning of CTLs prior to ip injection
      significantly delayed ip BLCL-derived tumor formation in vivo when compared to
      CTLs expanded in vitro using only IL2 (P = 0.04) and prevented tumor outgrowth in
      a significant proportion (60%) of mice (P = 0.02). Daily ip IL2 dosing of ip CTL
      inoculated mice significantly delayed tumor development in vivo (P = 0.004) and
      prevented tumor outgrowth in a significant proportion (78%) of mice (P = 0.02)
      when compared to animals dosed with vehicle only. In SCID mice, autologous CTLs,
      and CD8-enriched T cells, have significant capacity to hinder development of PTLD
      like tumors. Whilst studies are needed to delineate the role of cytokine
      conditioning and CD4-enriched T cells, the results suggest that IL2 plays a key
      role in supporting CTL funtion in vivo.

PMID- 21739451
TI  - Inverse association of IL28B genotype and liver mRNA expression of genes
      promoting or suppressing antiviral state.
AB  - High intrahepatic expression levels of interferon stimulated genes (ISGs) in
      chronic hepatitis C patients are associated with poor response to interferon plus
      ribavirin combination therapy. Expression levels of 16 genes (OAS1, PKR, MxA,
      ISG15, RIG-I, TLR8, IRF7, IRF9, NFKBIA, IL28A/IL28B, IL29, IL28RA, IL10RB,
      IFNAR2, and STAT1) that promote antiviral state and 4 genes (SOCS1, SOCS3,
      Zc3h12a, and A20) that suppress antiviral state were analyzed using real-time PCR
      assays in 133 liver biopsy samples from patients infected with genotypes 1 or 2.
      Expression levels of genes promoting antiviral state were positively correlated
      with each other but were not correlated with those that suppress antiviral state.
      Expression levels of some ISGs were inversely associated with common
      polymorphisms within the IL28B locus. Genes promoting antiviral state were
      expressed lower (e.g., ISG15, P = 1.42E-12 and MxA, P = 6.40E-11) in individuals
      with the protective rs12979860 CC genotype, and genes suppressing antiviral state
      were expressed higher (A20, P = 0.00107 and Zc3h12a, P = 0.00129, respectively),
      although some ISGs were not significant after the Bonferroni correction. The
      expression levels of both an antiviral (MxA) and a suppressor (SOCS1) ISG were
      independent predictors for non-response. These results suggest that rs12979860
      genotype may be associated with response to combination therapy through an
      inverse relationship between antiviral and suppressor ISGs in the liver.

PMID- 21739452
TI  - Prevalence of JC polyomavirus genomic sequences from the large T-antigen and non
      coding control regions among Bulgarian patients with primary brain tumors.
AB  - A total of 111 fresh brain biopsies from patients with primary brain tumors were
      examined for JC polyomavirus sequences from the Large T antigen encoding region
      (LT) and the viral non-coding control region (NCCR). SYBR Green and TaqMan real
      time polymerase chain reaction assays were used. In the glioblastoma group of 39
      patients 48.7% were positive for LT sequences. Among the astrocytoma group (19
      patients) and the oligodendroglioma group (12 patients) 31.6% and 33.3% were also
      positive. The prevalence of LT genomic sequences among the other groups was as
      follows: in 2 out of 3 oligoastrocytomas; in 3 out 5 gangliogliomas; in 2 out of
      5 meduloblastomas; in 1 out 3 pineocytomas; and in none of the tested 5
      ependimomas. All positive samples had a late threshold cycle that varied from 36
      to 49, indicative of very low starting viral number. Only 21 of all the 111
      samples were positive for NCCR. Low copy number in range of 10-1,000 was present.
      Notably, only 8 of all NCCR positive specimens were also LT positive. It might be
      suggested that the disproportion between the results for LT and NCCR is either
      due to clonally integrated LT fragments, with loss of genetic material, or
      changes in the NCCR. The latter would alter the productive course of the
      infection and may establish a premise for continuous interaction of viral
      regulatory proteins with cell molecules that are responsible for the control of
      the cell cycle. This may lead subsequently to malignant transformation.

PMID- 21739453
TI  - Molecular characterization of measles virus strains causing subacute sclerosing
      panencephalitis in France in 1977 and 2007.
AB  - Measles virus strains from two subacute sclerosing panencephalitis (SSPE) cases
      diagnosed in 1977 (Laine strain) and in 2007 (Hoedts strain) were studied.
      Phylogenetic analysis based on C-terminal part of the nucleoprotein and the
      entire H gene showed that Hoedts strain, circulating in France presumably in the
      1980s, belonged to genotype C2. However, Laine strain, suspected to have
      circulated between 1940s and 1960s, could not be assigned to any known measles
      virus genotypes. Sequences analysis of the Laine strain suggested that it
      originated from a measles virus that may have circulating at the same period as
      the Edmonston strain. The analysis of the whole genome of both SSPE strains
      revealed biased hypermutations in M, F, and H gene. Some of these mutations like
      the L165P found in the M protein sequence of the Laine strain, the amino acid
      position 94, where a mutation M94V was found in the F protein sequence of the
      Hoedts strain are known to play an important role in the glycoprotein interaction
      and to impair the ability of measles virus strain to produce cell-free infectious
      viral particles.This is the first study on molecular characterization of the
      entire coding region of measles virus isolated from SSPE cases in France.

PMID- 21739454
TI  - Improvement of the specificity of a pan-viral microarray by using genus-specific
      oligonucleotides and reduction of interference by host genomes.
AB  - Rapid detection of viral pathogens is crucial for antiviral therapy. High-density
      60-70-mer oligonucleotide microarrays have been explored for broad detection of
      many viruses. However, relatively low specificity and the complex analytical
      processes are the major limitations when pan-viral oligonucleotide microarrays
      are used to detect viral pathogens. In this study, genus-specific
      oligonucleotides were used as probes and modified sample preparations were
      carried out to improve the specificity and accuracy of the pan-viral
      oligonucleotide microarray. Genus-specific 63-mer oligonucleotide probes were
      used for screening human pathogenic RNA viruses. A total of 628 oligonucleotide
      probes covering 32 RNA viral genera from 14 viral families were used. The number
      of oligonucleotide probes was decreased to simplify the analytical process of
      hybridization and to minimize cross-hybridization. Host genomes were removed by
      DNase I/RNase T1 digestion before viral nucleic acid extraction, and non
      ribosomal hexanucleotides were used for reverse transcription to minimize
      interference of host genomes. Cultured viruses were used for microarray
      validation. The microarray was validated by cultured isolates that belonged to
      five viral genera. By using DNase I/RNase T1 digestion before viral nucleic acid
      extraction and non-ribosomal hexanucleotides for reverse transcription, the
      specificity of the microarray was improved. Furthermore, the analytical process
      of hybridization results was simplified. The specificity of pan-viral microarray
      could be improved by using genus-specific oligonucleotides as probes and by using
      non-ribosomal hexanucleotides for reverse transcription. Combined with subsequent
      degenerate reverse transcriptase-polymerase chain reaction and sequencing
      processes, this improved genus-specific oligonucleotides microarray provides a
      relatively flexible strategy for diagnosis of RNA virus diseases.

PMID- 21739455
TI  - Monitoring of group C rotavirus in children with acute gastroenteritis in Brazil:
      an emergent epidemiological issue after rotavirus vaccine?
AB  - Group C rotavirus (GpCRV) has a worldwide distribution; however, its epidemiology
      and ecology are still unclear. Evidence for a possible zoonotic role has been
      postulated recently for Brazilian children strains. The aim of this study was to
      monitor GpCRV in children <=15 years with acute gastroenteritis during the 2007
      2010 national Brazilian rotavirus surveillance, and to undertake the molecular
      characterization of the major VP6 capsid protein. A total of 3,019 fecal samples
      were first screened for Group A rotavirus (GpARV). A total of 2,205 GpARV ELISA
      negative samples were tested further for the presence of GpCRV by SDS-PAGE,
      electronic microscopy, and RT-PCR for the VP6 gene. The genetic diversity of
      GpCRV was carried out by sequencing the VP6 gene. GpARV and GpCRV infections were
      detected in 24.6% (742/3,019) and 0.3% (8/3,019), respectively. The GpCRV
      detection rate increased from 0.2% (1/422) in 2007 to 1% (7/708) in 2008, and
      GpCRV cases were not detected in 2009 and 2010. The phylogenetic analysis
      indicated that the strains belonged to the human lineage, and showed a genetic
      relationship with the GpCRV strain from Japan isolated in 2009. None of the study
      sequences was related closely to animal GpCRV strains. This study provides
      further evidence that GpCRV is a minor cause of acute childhood gastroenteritis
      in Brazil, and does not suggest that GpCRV may assume epidemiological importance
      in the future, even after the introduction of a GpARV vaccine. In addition, the
      molecular analyses of the GpCRV samples in this study do not support the zoonotic
      hypothesis.

PMID- 21739456
TI  - Case report: detection of rotavirus RNA in the cerebrospinal fluid of a child
      with rotavirus gastroenteritis and meningism.
AB  - Although case reports have described detection of rotavirus (RV) in
      extraintestinal sites such as the liver, kidney, and central nervous system (CNS)
      of children with RV gastroenteritis, CNS localization in RV infection seems to be
      rare. RT-PCR and nucleotide sequencing detected a G1P[8] strain in the stool and
      cerebrospinal fluid (CSF) samples of a patient with concurrent RV-associated
      enteritis and CNS signs. Upon sequence analysis, the viruses detected in the CSF
      was identical to the virus detected in the stools. In the VP7- and VP4-based
      phylogenetic dendograms the strain clustered within the G1-Ic sub-lineage and the
      P[8]-III lineage. This study supports the hypothesis that RV infection was able
      to spread from the intestinal tract to the CNS, and likely played a role in the
      onset of neurological disease.

PMID- 21739457
TI  - Molecular and clinical effects of betamethasone in human T-cell lymphotropic
      virus type-I-associated myelopathy/tropical spastic paraparesis patients.
AB  - There is no effective therapy for human T-cell lymphotropic virus type I (HTLV-I)
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). Glucocorticoids are
      effective to reduce the motor disability in these patients, but its role as anti
      spastic drugs is unknown. Here it is reported the use of corticosteroids in
      HAM/TSP. The goal was to find reliable molecular markers linked to treatment
      effectiveness. The clinical efficacy of corticosteroids was studied in 22
      HAM/TSP. The treatment was a single dose of 7.0 mg of systemic betamethasone. Pre
      treatment samples were obtained immediately before steroid administration and
      post-treatment samples were collected after 5 days. Neurological disability was
      evaluated by the Osame's Motor Disability Scales. Relative levels of Tax, Foxp3,
      IL-10, TGF-beta, CTLA-4, and GITR mRNA were measured and the percentage of CD4(+)
      Foxp3(+) and CD4(+) Tax(+) populations was quantified in PBMCs by real-time PCR
      and flow cytometry, respectively. The same parameters were studied in eight
      untreated carriers. Betamethasone treatment showed neurological improvement in 21
      HAM/TSP patients, with one patient without response to treatment. This therapy
      was associated with a decrease in Tax mRNA load and CD4(+) Tax(+) T cells in
      HAM/TSP. Simultaneously, an increase in Foxp3 mRNA and CD4(+) Foxp3(+) T cell was
      detected in these patients. The other markers studied had no significant changes
      after treatment. Clinical improvement in betamethasone-treated HAM/TSP was
      associated with an inverse relationship between a decrease in Tax and an increase
      in Foxp3 at the mRNA and protein levels. These results suggest that both Tax and
      Foxp3 may represent potential biomarkers for drug treatment assessments in
      HAM/TSP.

PMID- 21739458
TI  - Development and clinical validation of multiplex TaqMan(r) assays for rapid
      diagnosis of viral gastroenteritis.
AB  - There is a need to provide rapid, sensitive, and often high throughput detection
      of pathogens in diagnostic virology. Viral gastroenteritis is a serious health
      issue often leading to hospitalization in the young, the immunocompromised and
      the elderly. The common causes of viral gastroenteritis include rotavirus,
      norovirus (genogroups I and II), astrovirus, and group F adenoviruses (serotypes
      40 and 41). This article describes the work-up of two internally controlled
      multiplex, probe-based PCR assays and reports on the clinical validation over a 3
      year period, March 2007 to February 2010. Multiplex assays were developed using a
      combination of TaqManTM and minor groove binder (MGBTM) hydrolysis probes. The
      assays were validated using a panel of 137 specimens, previously positive via a
      nested gel-based assay. The assays had improved sensitivity for adenovirus,
      rotavirus, and norovirus (97.3% vs. 86.1%, 100% vs. 87.8%, and 95.1% vs. 79.5%,
      respectively) and also more specific for targets adenovirus, rotavirus, and
      norovirus (99% vs. 95.2%, 100% vs. 93.6%, and 97.9% vs. 92.3%, respectively). For
      the specimens tested, both assays had equal sensitivity and specificity for
      astrovirus (100%). Overall the probe-based assays detected 16 more positive
      specimens than the nested gel-based assay. Post-introduction to the routine
      diagnostic service, a total of 9,846 specimens were processed with multiplex 1
      and 2 (7,053 pediatric, 2,793 adult) over the 3-year study period. This
      clinically validated, probe-based multiplex testing algorithm allows highly
      sensitive and timely diagnosis of the four most prominent causes of viral
      gastroenteritis.

PMID- 21739459
TI  - Molecular characterization of rotavirus strains from children with diarrhea in
      Italy, 2007-2009.
AB  - The surveillance network RotaNet-Italia was established in 2007 in order to
      investigate the diversity of co-circulating rotavirus strains in Italy, and to
      provide a baseline for future assessment of possible effects of vaccine
      implementation in selecting novel versus common rotavirus strains. A total of
      2,645 rotavirus strains from pediatric patients with acute diarrhea were
      collected over three consecutive seasons from September 2006 through August 2009,
      and partially characterized by standardized multiplex RT-PCR. Most of strains
      (89.1%) belonged to genotypes G1-G4, and G9, associated with either P[8] or P[4],
      commonly found in humans worldwide. However, in at least 2.0% of cases, viruses
      exhibited either a G or P type typical of animal viral strains, suggesting gene
      reassortment events between rotaviruses of different origin. Mixed infections
      with two or more rotavirus strains were observed frequently (7.6% of patients),
      and depended on the frequencies of co-circulating rotaviruses of one particular
      genotype. The numbers and genotypes of likely natural reassortants of common
      genotype rotaviruses were found to be correlated with the observed numbers and
      genotypes of mixed infections. Large variation in the relative frequency of
      different rotavirus genotypes was observed between different seasons and/or areas
      of Italy, suggesting independent evolution or differential introduction of viral
      strains with respect to both time and space.

PMID- 21739461
TI  - How viral infections enhance or prevent type 1 diabetes-from mouse to man.

PMID- 21739462
TI  - Current views on Ljungan virus and its relationship to human diabetes.

PMID- 21739463
TI  - Proteomic analysis of the interleukin-4 (IL-4) response in hepatitis B virus
      positive human hepatocelluar carcinoma cell line HepG2.2.15.
AB  - Hepatitis B virus (HBV) infection is the leading cause of liver cirrhosis and
      hepatocellular carcinoma worldwide. In recent decades, significant progress
      toward understanding the molecular virology and pathogenesis of HBV infection has
      been made. In addition, multiple treatment modalities have been developed for
      persons with HBV infection. In the present study, we demonstrated that IL-4
      inhibits the expression of hepatitis B surface antigen and hepatitis B e antigen
      in a HBV stably transfected hepatocellular carcinoma cell line (HepG2.2.15). To
      reveal the anti-HBV mechanism of IL-4 by proteomics, 2-DE and MS technology were
      utilized to profile global changes in protein expression in HepG2.2.15 cells
      after IL-4 treatment. A total of 56 differentially expressed proteins were
      identified in IL-4-treated HepG2.2.15 cells. To find out the interaction of these
      changed proteins by bioinformatics, signaling network analysis with the STRING
      tool showed that the identified proteins are primarily involved in transcription
      and proteolysis. Taken together, these results offer valuable clues for
      understanding the molecular mechanisms of the IL-4-mediated anti-HBV response.

PMID- 21739464
TI  - Profiling gastrin-releasing peptide receptor in prostate tissues: clinical
      implications and molecular correlates.
AB  - BACKGROUND: The gastrin-releasing peptide receptor (GRPR) has emerged as an
      attractive target for both therapeutic and diagnostic appliances, but has only
      insufficiently been characterized in the human prostate so far. The aim of this
      study is to profile GRPR in a large cohort and correlate it with
      clinicopathologic and molecular parameters. METHODS: Benign and malignant
      (primary carcinoma, metastases, and castration-resistant prostate cancer)
      prostate samples from 530 patients were analyzed immunohistochemically for GRPR,
      androgen receptor and Cyclin D1 expression. Staining intensity was assessed
      assigning a semiquantitative score to each sample. RESULTS: Normal prostate
      tissues were mostly GRPR negative, significantly higher expression rates were
      seen in primary carcinomas and metastases. Significant inverse correlations were
      found for GRPR and increasing Gleason score, PSA value, and tumor size. A
      stratified Kaplan-Meyer analysis for GRPR and high AR expression shows a
      significant prognostic advantage for high GRPR expression, whereas GRPR
      expression alone shows no independent prognostic value. Highly significant
      correlations for GRPR, AR, and Cyclin D1 were found. CONCLUSIONS: Our data show
      that GRPR is overexpressed in prostate cancer, particularly of lower grade and
      smaller size. These findings constitute a caveat for the use of GRPR as a target
      for diagnostic or therapeutic approaches to high grade or progressed prostate
      cancer.

PMID- 21739465
TI  - Altered prostate epithelial development in mice lacking the androgen receptor in
      stromal fibroblasts.
AB  - BACKGROUND: Androgens and the androgen receptor (AR) play important roles in the
      development of male urogenital organs. We previously found that mice with total
      AR knockout (ARKO) and epithelial ARKO failed to develop normal prostate with
      loss of differentiation. We have recently knocked out AR gene in smooth muscle
      cells and found the reduced luminal infolding and IGF-1 production in the mouse
      prostate. However, AR roles of stromal fibroblasts in prostate development remain
      unclear. METHODS: To further probe the stromal fibroblast AR roles in prostate
      development, we generated tissue-selective knockout mice with the AR gene deleted
      in stromal fibroblasts (FSP-ARKO). We also used primary culture stromal cells to
      confirm the in vivo data and investigate mechanisms related to prostate
      development. RESULTS: The results showed cellular alterations in the FSP-ARKO
      mouse prostate with decreased epithelial proliferation, increased apoptosis, and
      decreased collagen composition. Further mechanistic studies demonstrated that FSP
      ARKO mice have defects in the expression of prostate stromal growth factors. To
      further confirm these in vivo findings, we prepared primary cultured mouse
      prostate stromal cells and found knocking down the stromal AR could result in
      growth retardation of prostate stromal cells and co-cultured prostate epithelial
      cells, as well as decrease of some stromal growth factors. CONCLUSIONS: Our FSP
      ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system
      for the requirement of stromal fibroblast AR to maintain the normal development
      of the prostate, but may also suggest the selective knockdown of stromal AR might
      become a potential therapeutic approach to battle prostate hyperplasia and
      cancer.

PMID- 21739466
TI  - Intriguing location of myeloperoxidase in the prostate: a preliminary
      immunohistochemical study.
AB  - BACKGROUND: Myeloperoxidase (MPO) is a member of the peroxidase-cyclooxygenase
      superfamily, which is secreted from stimulated leucocytes at inflammatory sites.
      It is well known that MPO catalyses oxidation reactions via the release of
      reactive halogenating and nitrating species and thus induces tissue damage.
      Several studies have already implicated MPO in the development of neoplasia.
      Chronic or recurrent prostatic inflammation has long been recognized as having
      the potential to initiate and promote the development of prostate cancer. The
      objective was to investigate whether MPO is present in the prostate. METHODS:
      Human prostate material was obtained from biopsies, transurethral resections of
      the prostate (TURP), prostatic adenomectomies, and retropubic radical
      prostatectomies. Twenty-nine slides of normal prostate tissue, benign prostatic
      hyperplasia (BPH), and prostate cancer were reviewed by a pathologist.
      Immunohistochemical analysis using MPO-specific human antibody was performed to
      detect MPO in the prostate tissue. RESULTS: Immunocytohistochemistry showed
      cellular colocalization of MPO in the secretory epithelial cells of the prostate
      with staining varying from light to strong intensity. Staining in the glandular
      apical snouts was often reinforced although staining of basal as well as of
      luminal glandular cells was also present. CONCLUSIONS: We identified, for the
      first time, the presence of MPO at the surface of prostatic epithelial cells. In
      view of the pro-oxidant properties of this enzyme, further research is needed to
      define whether MPO contributes to the development of prostatic lesions.

PMID- 21739467
TI  - Genes inducing iPS phenotype play a role in hepatocyte survival and proliferation
      in vitro and liver regeneration in vivo.
AB  - Reprogramming factors have been used to induce pluripotent stem cells as an
      alternative to somatic cell nuclear transfer technology in studies targeting
      disease models and regenerative medicine. The neuronal repressor RE-1 silencing
      transcription factor (REST) maintains self-renewal and pluripotency in mouse
      embryonic stem cells by maintaining the expression of Oct3/4, Nanog, and cMyc. We
      report that primary hepatocytes express REST and most of the reprogramming
      factors in culture. Their expression is up-regulated by hepatocyte growth factor
      (HGF) and epidermal growth factor (EGF). REST inhibition results in down
      regulation of reprogramming factor expression, increased apoptosis, decreased
      proliferation, and cell death. The reprogramming factors are also up-regulated
      after 70% partial hepatectomy in vivo. CONCLUSION: These findings show that genes
      inducing the iPS phenotype, even though expressed at lower levels than embryonic
      stem cells, nonetheless are associated with control of apoptosis and cell
      proliferation in hepatocytes in culture and may play a role in such processes
      during liver regeneration.

PMID- 21739468
TI  - Effects of computer keyboarding on ultrasonographic measures of the median nerve.
AB  - BACKGROUND: Keyboarding is a highly repetitive daily task and has been linked to
      musculoskeletal disorders of the upper extremity. However, the effect of
      keyboarding on median nerve injuries is not well understood. The purpose of this
      study was to use ultrasonographic measurements to determine whether continuous
      keyboarding can cause acute changes in the median nerve. METHODS: Ultrasound
      images of the median nerve from 21 volunteers were captured at the levels of the
      pisiform and distal radius prior to and following a prolonged keyboarding task
      (i.e., 1 hr of continuous keyboarding). Images were analyzed by a blinded
      investigator to quantify the median nerve characteristics. Changes in the median
      nerve ultrasonographic measures as a result of continuous keyboarding task were
      evaluated. RESULTS: Cross-sectional areas at the pisiform level were
      significantly larger in both dominant (P = 0.004) and non-dominant (P = 0.001)
      hands following the keyboarding task. Swelling ratio was significantly greater in
      the dominant hand (P = 0.020) after 60 min of keyboarding when compared to the
      baseline measures. Flattening ratios were not significantly different in either
      hand as a result of keyboarding. CONCLUSION: We were able to detect an acute
      increase in the area of the median nerve following 1 hr of keyboarding with a
      computer keyboard. This suggests that keyboarding has an impact on the median
      nerve. Further studies are required to understand this relationship, which would
      provide insight into the pathophysiology of median neuropathies such as carpal
      tunnel syndrome.

PMID- 21739469
TI  - Development and application of a population-based system for workplace violence
      surveillance in hospitals.
AB  - BACKGROUND: A unique and comprehensive reporting and population-based violence
      surveillance system in a multi-site hospital system is presented. METHODS:
      Incidence rates and rate ratios (RR) were calculated by year, hospital, violence
      type, and job category in six hospitals, 2003-2008. RESULTS: Incidence rates per
      hospital for the 6-year period ranged from a low of 1.52 to a high of 10.89
      incidents/100 full-time equivalents (FTEs), with the highest risk at a hospital
      with an outpatient mental health facility (RR = 7.16, 95%CI = 5.17-10.26). Rates
      for worker-on-worker violence exceeded rates for patient-to-worker violence from
      2004 to 2008. Mental health technicians (RR = 13.82, 95%CI =  1.13-17.29) and
      security personnel (RR = 2.25, CI = 1.68-3.00) were at greatest risk for
      violence. CONCLUSIONS: This surveillance system provides ongoing information on
      professional groups and hospital departments at risk and trends in violence
      reporting over time. It can be used to determine where appropriate violence
      prevention efforts are most needed, and to evaluate violence interventions.

PMID- 21739470
TI  - Diagnostic criteria for depression in Parkinson's disease: a study of symptom
      patterns using latent class analysis.
AB  - Although major depression is one of the most frequent psychiatric disorders among
      patients with Parkinson's disease, diagnostic criteria have yet to be validated.
      The main aim of our study was to validate depressive symptoms using latent class
      analysis for use as diagnostic criteria for major depression in Parkinson's
      disease. We examined a consecutive series of 259 patients with Parkinson's
      disease admitted to 2 movement disorders clinics for regular follow-ups. All
      patients were assessed with a comprehensive psychiatric interview that included
      structured assessments for depression, anxiety, and apathy. The main finding was
      that all 9 Diagnostic and Statistical Manual (4th edition) diagnostic criteria
      for major depression (ie, depressed mood, diminished interest or pleasure, weight
      or appetite changes, sleep changes, psychomotor changes, loss of energy, feelings
      of worthlessness or inappropriate guilt, poor concentration, and suicidal
      ideation) identified a patient class (severe depression group) with high
      statistical significance. Latent class analysis also demonstrated a patient class
      with minimal depressive symptoms (no-depression group), and a third patient class
      with intermediate depressive symptoms (moderate depression). Anxiety and apathy
      were both significant comorbid conditions of moderate and severe depression.
      Taken together, our findings support the use of the full Diagnostic and
      Statistical Manual (4th edition) criteria for major depression for use in
      clinical practice and research in Parkinson's disease and suggest that anxiety
      may be included as an additional diagnostic criterion.

PMID- 21739471
TI  - Examination of central gait control mechanisms in Parkinson's disease using
      movement-related potentials.
AB  - Gait disorders are common in people with Parkinson's disease. The pathophysiology
      of these disorders is not fully understood. Movement-related potentials reflect
      supplementary motor area activity associated with the preparation and execution
      of voluntary movement. Our aim was to investigate movement-related potentials
      associated with gait disturbances in patients with Parkinson's disease, as
      reflected by gait hypokinesia and initiation difficulties, in order to better
      understand the role of the basal ganglia in the pathogenesis of these conditions.
      Movement-related potentials were back-averaged from electroencephalography
      recordings performed on 11 participants with Parkinson's disease with no gait
      initiation difficulties, 9 participants with Parkinson's disease who suffered
      from gait initiation difficulties, 12 young healthy adults, and 8 healthy older
      adults. Participants took 3 steps forward, stepping off a force plate. Trigger
      signals from the force plate and electromyographic activity of the tibialis
      anterior muscle were used to identify gait initiation time. Participants' stride
      length was also measured using a 3-dimensional motion analysis system. Movement
      related potentials showed significant group differences between the healthy young
      adults and the 2 Parkinson's disease groups as well as the Parkinson's disease
      group as a whole. No significant difference was found between the participants
      with Parkinson's disease and age-matched controls. A significant inverse
      relationship between movement-related potentials and stride length was found in
      patients with Parkinson's disease who did not experience gait initiation
      difficulties but not in those who did have this symptom. Gait-generated movement
      related potentials appear to show electrical evidence of cortical disturbances
      correlated with stride length reduction in patients with Parkinson's disease
      without gait initiation difficulties.

PMID- 21739472
TI  - Obesity, diabetes, and risk of Parkinson's disease.
AB  - The aim of this work was to investigate whether obesity and diabetes are related
      to risk of Parkinson's disease. We prospectively followed 147,096 participants in
      the Cancer Prevention Study II Nutrition Cohort from 1992 to 2005. Participants
      provided information on anthropometric variables and medical history at baseline
      and on waist circumference in 1997. Incident cases of Parkinson's disease (n =
      656) were confirmed by treating neurologists and medical record review. Relative
      risks were estimated using proportional hazards models, adjusting for age,
      gender, smoking, and other risk factors. Neither body mass index nor waist
      circumference significantly predicted Parkinson's disease risk. Relative risk
      comparing individuals with a baseline body mass index of >= 30 to those with a
      body mass index <23 was 1.00 (95% confidence interval: 0.75, 1.34; P trend:
      0.79), and that comparing individuals with a waist circumference in the top
      category (>= 40.3 inches in men and >= 35 inches in women) to those in the bottom
      category (<34.5 inches in men and <28 inches in women) was 1.35 (95% confidence
      interval: 0.95, 1.93; P trend: 0.08). History of diabetes was not significantly
      associated with Parkinson's disease risk (combined relative risks = 0.88; 95%
      confidence interval: 0.62, 1.25; P heterogeneity = 0.96). In addition, neither
      body mass index at age 18 nor changes in weight between age 18 and baseline were
      significantly associated with Parkinson's disease risk. The results did not
      differ significantly by gender. Our results do not provide evidence for a
      relationship between body mass index, weight change, waist circumference, or
      baseline diabetes and risk of Parkinson's disease.

PMID- 21739474
TI  - Crystal structure of FAF1 UBX domain in complex with p97/VCP N domain reveals a
      conformational change in the conserved FcisP touch-turn motif of UBX domain.

PMID- 21739475
TI  - Clinical anatomy of the coccyx: A systematic review.
AB  - The coccyx has been relatively neglected in anatomical research which is
      surprising given the population prevalence of coccydynia and our inadequate
      understanding of its etiology. This systematic review analyzes available
      information on the clinical anatomy of the coccyx. A literature search using five
      electronic databases and standard anatomy reference texts was conducted yielding
      61 primary and 7 secondary English-language sources. This was supplemented by a
      manual search of selected historical foreign language articles. The coccygeal
      vertebrae, associated joints, ligaments and muscles, coccygeal movements, nerves,
      and blood supply were analyzed in detail. Although the musculoskeletal aspects of
      the coccyx are reasonably well described, the precise anatomy of the coccygeal
      plexus and its distribution, the function of the coccygeal body, and the anatomy
      of the sacrococcygeal zygapophyseal joints are poorly documented. Further
      research into the anatomy of the coccyx may clarify the etiopathogenesis of
      coccydynia which remains uncertain in one-third of affected patients.

PMID- 21739476
TI  - Giovanni Maria Lancisi (1654-1720): anatomist and papal physician.
AB  - Giovanni Maria Lancisi (1654-1720) was an Italian physician who made significant
      contributions to many fields of medicine. De subitaneis mortibus was the first
      autoptic manuscript, suggesting that myocardial disease was a factor in a 1706
      sudden death epidemic in Rome. His book De motu cordis et aneurysmatibus
      described the pathology and etiology of aneurysms, and Tractatus de urinis was
      the first discussion of the physiological mechanism of urine formation. Arguably,
      Lancisi's most notable medical contribution was the anatomical description of the
      medial longitudinal striae of the corpus callosum, in addition to other documents
      he wrote in the field of neurology. Aside from his medical work, Lancisi
      developed the "stamping out" method for eradication of the cattle plague in
      Europe, and he contributed to early work in malarial research. Lancisi was a
      multifaceted man with vast interests outside of medicine including language and
      literature. Over the course of his life, Lancisi opened his own medical library,
      was chair of anatomy for 13 years at Sapienza University, and served as papal
      physician to three popes.

PMID- 21739477
TI  - Anatomical verification and designation of the superficial layer of the
      temporalis muscle.
AB  - The temporalis muscle, which is one of the masticatory muscles, enables elevation
      and retraction of the mandible. Direct injury to the temporalis muscle, facial
      nerve, or temporal fat pad during cranial-base surgery can cause temporal
      hollowing. The temporalis muscle is currently described in almost all atlases and
      textbooks as comprising a single layer. In this study, a superficial layer of the
      temporalis muscle is described, clarifying the anatomy of this muscle. Twenty
      heads of adult cadavers were dissected. The gross anatomy of the temporalis
      muscle was examined after removing the skin, subcutaneous tissue, superficial
      temporal fascia, and deep temporal fascia. The superficial layer of the
      temporalis muscle was clearly distinguishable from the deep layer. The
      superficial layer originated from the same region as the deep layer, and the
      muscle fibers of the two layers were intermingled in the superior part of the
      muscle. The deep layer of the temporalis muscle, which is referred to in
      textbooks and atlases simply as the temporalis muscle, was exposed after removing
      the superficial layer. The existence of this superficial layer was confirmed
      herein both histologically and by magnetic resonance imaging. Henceforth, the
      superficial layer of the temporalis muscle must be included in descriptions of
      the temporalis muscle in anatomy textbooks and atlases. The findings of this
      study are important not only from the perspective of simply acquiring correct
      anatomical knowledge, but also from the surgical perspective in preventing
      temporal hollowing during related surgical procedures.

PMID- 21739478
TI  - Downregulation of Mig-6 in nonsmall-cell lung cancer is associated with EGFR
      signaling.
AB  - Downregulation of Mig-6 expression has been implicated in several human cancers
      and its loss can lead to prolonged activation of EGFR and carcinogenesis. The
      present study aimed to investigate the clinical significance of loss of Mig-6
      expression in nonsmall-cell lung cancer (NSCLC) and the biological functions of
      Mig-6 in NSCLC cell lines. Mig-6 expression was downregulated in 47/91 (51.6%)
      cases of NSCLC that were examined. Mig-6 downregulation significantly correlated
      with poor differentiation (P = 0.0131), histological type (P = 0.0021), and EGFR
      expression (P = 0.003). In addition, knockdown of Mig-6 expression in H1299 and
      BE1 cells promoted EGF-induced tumor cell proliferation and migration.
      Furthermore, Mig-6 knockdown led to a significant increase in phospho-AKT,
      phospho-ERK, phospho-EGFR as well as MMP-2 and MMP-9 levels. These results
      indicate that downregulated Mig-6 in NSCLC tissues may serve as a new marker that
      can predict the activation of EGFR signaling pathway.

PMID- 21739479
TI  - Bim contributes to phenethyl isothiocyanate-induced apoptosis in breast cancer
      cells.
AB  - Phenethyl isothiocyanate (PEITC) is a highly promising cancer chemopreventive
      constituent of cruciferous vegetables (e.g., watercress) with in vivo efficacy in
      experimental rodent cancer models. Research thus far implicates apoptosis
      induction in cancer chemopreventive response to PEITC, but the mechanism of
      proapoptotic effect is not fully understood. The present study demonstrates that
      p53 upregulated modulator of apoptosis (PUMA)-independent apoptosis by PEITC is
      mediated by B-cell lymphoma 2 interacting mediator of cell death (Bim). Exposure
      of a cell line (BRI-JM04) derived from spontaneously developing mammary tumor of
      a MMTV-neu transgenic mouse to pharmacological concentrations of PEITC resulted
      in decreased cell viability coupled with apoptosis induction, characterized by
      release of histone-associated DNA fragments into the cytosol and cleavage of poly
      (ADP-ribose)-polymerase and procaspase-3. The PEITC-induced apoptosis in BRI-JM04
      cells was associated with up-regulation of Bak, PUMA, and Bim (long and short
      forms of Bim), increased S65 phosphorylation of BimEL (extra-long form), and down
      regulation of Bcl-xL and Bcl-2. On the other hand, a non-tumorigenic human
      mammary epithelial cell line (MCF-10A) was significantly more resistant to PEITC
      induced apoptosis compared with BRI-JM04 despite induction of Bax and PUMA due to
      concomitant overexpression of anti-apoptotic proteins, including Bcl-xL, Bcl-2,
      and Mcl-1. Wild-type HCT-116 cells and its isogenic PUMA knockout variant
      exhibited comparable sensitivity to PEITC-induced apoptosis. On the other hand,
      small interfering RNA knockdown of Bim protein imparted partial but statistically
      significant protection against PEITC-induced apoptosis in BRI-JM04, MCF-7, and
      MDA-MB-231 cells. In conclusion, the present study provides novel insight into
      the mechanism of PEITC-induced apoptosis involving Bim.

PMID- 21739480
TI  - Potentially functional polymorphisms in DNA repair genes and non-small-cell lung
      cancer survival: a pathway-based analysis.
AB  - To assess systematically whether potentially functional polymorphisms in DNA
      repair genes influence the clinical behavior of non-small-cell lung cancer
      (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide
      polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC
      in a case-cohort of 568 lung cancer patients. SNPs associated with lung cancer
      prognosis primarily mapped to 14 genes in different repair pathways, and 6 SNPs
      were remained in the final model after multivariate stepwise Cox regression
      analysis: ATM rs189037; MRE11A rs11020802; ERCC2 rs1799793; MBD4 rs140693; XRCC1
      rs25487, and PMS1 rs5742933. In the combined analysis of these 6 SNPs, an
      increasing number of unfavorable loci was associated with a poorer prognosis (P
      for trend: <0.0001) and patients having 2-4 unfavorable loci had a 1.99-fold
      elevated risk of death 95% confidence interval (CI) = 1.58-2.50, compared with
      those carrying 0-1 unfavorable loci, and this elevated risk was more evident
      among stages I-II patients (hazard ratio = 3.04, 95% CI = 1.86-4.98, P for
      heterogeneity: 0.07). Furthermore, a significant effect of SNPs in nucleotide
      excision repair pathway on lung cancer survival was observed among 185 stages III
      IV patients treated with platinum-based chemotherapy without surgical operation:
      XPC rs2228000 (Ala499Val; P = 0.002) and ERCC1 rs11615 (Asn118Asn; P = 0.012).
      Our data indicate that potentially functional polymorphisms in DNA repair genes
      may serve as candidate prognostic markers of clinical outcome of NSCLC.

PMID- 21739481
TI  - The EP1 receptor for prostaglandin E2 promotes the development and progression of
      malignant murine skin tumors.
AB  - High levels of prostaglandin E2 (PGE2) synthesis resulting from the up-regulation
      of cyclooxygenase (COX)-2 has been shown to be critical for the development of
      non-melanoma skin tumors. This effect of PGE2 is likely mediated by one or more
      of its 4 G-protein coupled membrane receptors, EP1-4. A previous study showed
      that BK5.EP1 transgenic mice produced more carcinomas than wild type (WT) mice
      using initiation/promotion protocols, although the tumor response was dependent
      on the type of tumor promoter used. In this study, a single topical application
      of either 7,12-dimethylbenz[a]anthracene (DMBA) or benzo[a]pyrene (B[a]P), alone,
      was found to elicit squamous cell carcinomas (SCCs) in the BK5.EP1 transgenic
      mice, but not in WT mice. While the epidermis of both WT and transgenic mice was
      hyperplastic several days after DMBA, this effect regressed in the WT mice while
      proliferation continued in the transgenic mice. Several parameters associated
      with carcinogen initiation were measured and were found to be similar between
      genotypes, including CYP1B1 and aromatase expression, B[a]P adduct formation, Ras
      activity, and keratinocyte stem cell numbers. However, EP1 transgene expression
      elevated COX-2 levels in the epidermis and SCC could be completely prevented in
      DMBA-treated BK5.EP1 mice either by feeding the selective COX-2 inhibitor
      celecoxib in their diet or by crossing them onto a COX-2 null background. These
      data suggest that the tumor promoting/progressing effects of EP1 require the PGE2
      synthesized by COX-2.

PMID- 21739483
TI  - Occurrence of Aurora A positive multipolar mitoses in distinct molecular classes
      of colorectal carcinomas and effect of Aurora A inhibition.
AB  - Aurora A "over-"expression may induce supernumerary centrosomes, respective
      multipolar mitoses, and aneuploidy. Here, we examined Aurora A positive
      multipolar mitoses in aneuploid, microsatellite-stable (MSS, "CIN-type") versus
      near-diploid, microsatellite-instable (MSI, "MIN-type") colorectal carcinomas
      (CRC) and CRC cell lines as well as the effect of Aurora A inhibition in CRC cell
      lines. In situ, three-dimensional immunofluorescence (3D-IF) revealed Aurora A
      positive multipolar mitoses in both CIN- (n = 8) and MIN- (n = 10) type primary
      CRCs with similar frequencies (CIN: 27 +/- 14%; MIN: 34 +/- 14%, P = 0.224). In
      vitro, Aurora A positive multipolar mitoses were detected in asynchronized or
      thymidine synchronized CIN-type (HT29, CaCo-2), but not MIN-type (HCT116, DLD-1)
      CRC cells. Nocodazole treatment arrested mitotic cells with multiple centrosomal
      Aurora A signals in CIN- and MIN-type CRC cells, albeit to a lower extent in CaCo
      2 cells. This was associated with concomitant activation of Aurora A (T288
      phosphorylation) and Polo-like kinase 1 (PLK-1, T210 phosphorylation). Aurora A
      inhibition by siRNA resulted in increased apoptosis (>50%) in all cell lines, but
      did not abolish PLK-1 expression. Double 3D-IF revealed that Aurora A siRNA
      treated, still viable CIN-type (HT29, CaCo-2) CRC cells were Aurora A negative
      and mostly in prophase/(pro)metaphase with maintained phosphorylated PLK-1 T210
      expression. Aurora A positive multipolar mitoses occur in both aneuploid, CIN-
      and near-diploid MIN-type CRCs. This appears to be largely independent of Aurora
      A expression alone. Although Aurora A inhibition causes apoptosis in both CIN-
      and MIN-type CRC cells, remaining PLK-1 activation by other factors may affect
      therapeutic Aurora inhibition.

PMID- 21739482
TI  - MicroRNAs, diet, and cancer: new mechanistic insights on the epigenetic actions
      of phytochemicals.
AB  - There is growing interest in the epigenetic mechanisms that impact human health
      and disease, including the role of microRNAs (miRNAs). These small (18-25
      nucleotide), evolutionarily conserved, non-coding RNA molecules regulate gene
      expression in a post-transcriptional manner. Several well-orchestered regulatory
      mechanisms involving miRNAs have been identified, with the potential to target
      multiple signaling pathways dysregulated in cancer. Since the initial discovery
      of miRNAs, there has been progress towards therapeutic applications, and several
      natural and synthetic chemopreventive agents also have been evaluated as
      modulators of miRNA expression in different cancer types. This review summarizes
      the most up-to-date information related to miRNA biogenesis, and critically
      evaluates proposed miRNA regulatory mechanisms in relation to cancer signaling
      pathways, as well as other epigenetic modifications (DNA methylation patterns,
      histone marks) and their involvement in drug resistance. We also discuss the
      mechanisms by which dietary factors regulate miRNA expression, in the context of
      chemoprevention versus therapy.

PMID- 21739484
TI  - Hypoxia negatively regulates heparan sulfatase 2 expression in renal cancer cell
      lines.
AB  - Inactivation of von Hippel-Lindau (VHL), a tumor suppressor gene is often
      associated with clear cell renal cell carcinoma (ccRCC). VHL inactivation leads
      to multitude of responses including enhanced growth factor signaling such as
      bFGF2, SDF-1alpha, and HGF. Here, we have identified a novel VHL-inducible gene,
      heparan sulfatase 2 (HSulf-2) that attenuates heparan-binding growth factor such
      as bFGF2 signaling. VHL-mediated HIF-1 alpha degradation was essential to restore
      HSulf-2 expression. Mechanistically, HSulf-2 negatively regulated vimentin
      expression and knockdown of vimentin abolished cell migration. This study reveals
      a novel layer of regulation of heparan-binding growth factor signaling via
      modulation of heparan sulfate by HSulf-2 in ccRCC.

PMID- 21739487
TI  - Magnetically driven Janus micro-ellipsoids realized via asymmetric gathering of
      the magnetic charge.

PMID- 21739488
TI  - Toward flexible polymer and paper-based energy storage devices.
AB  - All-polymer and paper-based energy storage devices have significant inherent
      advantages in comparison with many currently employed batteries and
      supercapacitors regarding environmental friendliness, flexibility, cost and
      versatility. The research within this field is currently undergoing an exciting
      development as new polymers, composites and paper-based devices are being
      developed. In this report, we review recent progress concerning the development
      of flexible energy storage devices based on electronically conducting polymers
      and cellulose containing composites with particular emphasis on paper-based
      batteries and supercapacitors. We discuss recent progress in the development of
      the most commonly used electronically conducting polymers used in flexible device
      prototypes, the advantages and disadvantages of this type of energy storage
      devices, as well as the two main approaches used in the manufacturing of paper
      based charge storage devices. 

PMID- 21739489
TI  - Direct monolithic integration of organic photovoltaic circuits on unmodified
      paper.

PMID- 21739490
TI  - High electron mobility in air for N,N'-1H,1H-perfluorobutyldicyanoperylene
      carboxydi-imide solution-crystallized thin-film transistors on hydrophobic
      surfaces.

PMID- 21739491
TI  - Programmable, pattern-memorizing polymer surface.

PMID- 21739492
TI  - A new coordination polymer exhibiting unique 2D hydrogen-bonded (H2O)16 ring
      formation and water-dependent luminescence properties.
AB  - A new coordination polymer, [Zn(dpe)(bdc)].4H(2)O (ZndB; dpe=1,2-bis(4
      pyridyl)ethane, bdc(2-)=dianion of benzenedicarboxylic acid), which possesses a
      3D metal-organic framework (MOF) has been synthesized and structurally
      characterized. This 3D MOF is constructed by the assembly of helical channels
      filled with guest water molecules in both inner and outer regions of the channel.
      The resulting network also creates a 2D water layer containing hydrogen-bonded
      (H(2)O)(16) rings as the basic building units. Thermogravimetric and powder X-ray
      diffraction measurements of ZndB revealed a two-step weight loss of water
      molecules with a reversible water adsorption/desorption process in the inner
      channel for the first stage, and irreversible water desorption in the outer
      channel for the second stage. This spongelike property is manifested by the
      excimer emission originating from interaction between dpe (pi*) and the other dpe
      (pi) of the proximal helical channel, which is highly sensitive to the
      environmental perturbation. Powder X-ray analyses reveal that the dehydration
      process induces the readjustment of dpe pi-pi stacking distance/orientation,
      which results in dramatic luminescence changes from dim pale blue (lambda(em)~470
      nm) upon hydration to bright white-light generation (broad, lambda(em)~500-550
      nm) upon water depletion, accompanied by a ~100-fold increase in the emission
      intensity.

PMID- 21739493
TI  - Lanthanide ion extraction by trifluoromethyl-1,3-diketonate-functionalised ionic
      liquids adsorbed on silica.
AB  - While acetylacetone (acacH) derivatives are, upon deprotonation, ubiquitous
      ligands in coordination chemistry, their potential to form stable ionic liquids
      has not been studied so far. Here we describe a straightforward synthesis of
      novel trifluoroacetylacetone-functionalised imidazolium salts. These salts are
      built from an imidazolium ring substituted on one side with a flexible chain of
      fixed length carrying a terminal acacH group and on the opposite side a paraffin
      chain of various lengths. By changing the length of these flexible chains (n=4,
      8, 12) and the nature of the counter-anions (PF(6)(-), BF(4)(-), NTf(2)(-)), room
      temperature ionic liquids were produced. Their application for the extraction of
      lanthanide salts (Eu, Tb) from dilute aqueous solution has been investigated. The
      presence of a strong UV absorber (imidazolium ring, lambda(abs)=290 nm) allows
      photosensitisation of the Eu(III) and Tb(III) luminescence by efficient energy
      transfer, and thus extraction of these two lanthanides can be followed by
      fluorescence techniques. It appears that loading of the ionic liquids onto silica
      particles pre-treated with a dilute aqueous solution of NaOH is the most
      efficient way to obtain fast and almost quantitative (>99.9%) extraction of the
      metal ions as their diketonato complexes. The procedure is reproducible and the
      loaded SiO(2) particles can be simply treated with acid to strip the metal ions
      and regenerate the adsorbed (protonated) extractant.

PMID- 21739494
TI  - Synthesis of mesoporous NiO nanosheets for the detection of toxic NO2 gas.

PMID- 21739495
TI  - A texture analysis approach to quantify ventilation changes in hyperpolarised 3He
      MRI of the rat lung in an asthma model.
AB  - In preclinical research, allergic asthma is investigated in rats sensitised with
      the antigen ovalbumin (OVA), followed by a challenge with aerosolised OVA to
      induce an inflammatory reaction of the lower airways. This causes diffuse,
      nonfocal ventilation defects that lead to heterogeneously distributed signal
      intensities in hyperpolarised (HP) (3)He MR images, which are difficult to assess
      directly by diagnostic grading or volumetry. Texture analysis can characterise
      these changes and does not require segmentation of the lung structures prior to
      the analysis. The aim of this work was to evaluate a texture analysis approach to
      quantify changes in lung ventilation in HP (3)He MRI of OVA-challenged rats. OVA
      challenged animals were treated with two different compound doses to evaluate the
      sensitivity of the texture analysis. Four groups were investigated using HP (3)He
      MRI at 4.7 T: controls, vehicle-treated, and low- and high-dose budesonide
      treated rats. In addition, broncho-alveolar lavage was performed and the
      eosinophil cell count was used as a biological reference marker. First-order
      texture, geometrical features and features based on second-order statistics using
      run-length and grey-level co-occurrence matrices were calculated. In addition,
      wavelet transforms were applied to compute first-order statistics on multiple
      scales. The texture analysis was able to show significant differences between the
      control and untreated vehicle groups as well as between the vehicle and treatment
      groups. This is in agreement with the findings of the eosinophil cell counts,
      which were used as a marker for the severity of inflammation. However, not all
      features used in the different texture analysis methods could differentiate
      between the treatment groups. In conclusion, texture analysis can be used to
      quantify changes in lung ventilation as measured with HP (3)He MRI after
      therapeutic intervention with budesonide.

PMID- 21739496
TI  - Isolation of high quality RNA from cereal seeds containing high levels of starch.
AB  - INTRODUCTION: Cereals are an important source of food, feed and fuel with a
      rapidly increasing global demand. However, cereal seeds contain high levels of
      starch and polysaccharides, making the isolation of high quality RNA extremely
      difficult. OBJECTIVE: To develop a novel method for extracting high quality total
      RNA from various starch- and polysaccharides-rich cereal seeds, such as maize,
      rice, sorghum and wheat. METHODOLOGY: We developed a modified sodium dodecyl
      sulphate (SDS)/TRIzol method. The combined use of a Tris buffer (pH 9.0) and SDS
      before TRIzol extraction effectively resolved the problem of seed homogenate
      solidification in such a buffer. A high concentration of SDS was used separately,
      not only to promote cell lysis but also to effectively dissolve seed sample
      containing high levels of starch. Moreover, acid phenol saturated with 0.1  M
      citrate buffer (pH 4.3) was used to separate RNA from DNAs, proteins and high
      levels of starch. This rapid protocol was compared with other RNA isolation
      methods preferentially used for plants rich in polysaccharides and secondary
      metabolites. RESULTS: Gel electrophoresis analysis indicated that the extracted
      total RNA had good integrity without apparent DNA contamination. Furthermore, an
      A260/280 ratio of approximately 2.0, an A260/230 ratio of more than 2.0 and RIN
      values of more than 8.6 indicated that the isolated RNA was of high purity. The
      isolated RNA was suitable for subsequent molecular manipulations, such as reverse
      transcription polymerase chain reaction (PCR), rapid amplification of cDNA ends
      (RACE) and real-time PCR. CONCLUSION: The study has described an easy, efficient
      and highly reproducible method for RNA isolation from various cereal seeds.

PMID- 21739497
TI  - Prevention of preterm delivery in twin gestations (PREDICT): a multicenter,
      randomized, placebo-controlled trial on the effect of vaginal micronized
      progesterone.
AB  - OBJECTIVE: Studies on high-risk singleton gestations have shown a preventive
      effect of progesterone treatment on preterm delivery. This study was conducted to
      investigate the preventive effect of vaginal micronized progesterone in a large
      population of twin gestations. METHODS: This was a double-blind, placebo
      controlled randomized trial performed in 17 centers in Denmark and Austria. Women
      with twin gestations were randomized to daily treatment with progesterone
      pessaries or apparently identical placebo pessaries, starting from 20-24 weeks
      until 34 weeks' gestation. Primary outcome was incidence of delivery before 34
      weeks' gestation. Secondary outcomes were maternal and neonatal complications and
      long-term infant follow-up, by Ages and Stages Questionnaire (ASQ), 6 months and
      18 months after the expected date of delivery. We also updated a published meta
      analysis to include our data and those of another recently published twin trial.
      RESULTS: A total of 677 women were randomized to the two treatments. Two women in
      the placebo group were lost to follow-up. Baseline characteristics for the groups
      were similar. Incidence of delivery before 34 weeks was 15.3% in the progesterone
      group vs 18.5% in the placebo group (odds ratio, 0.8 (95% CI, 0.5-1.2)). Risks of
      maternal and neonatal complications were comparable for the two groups. Mean ASQ
      scores at 6 months and 18 months were not significantly different between the two
      groups (215 for infants in the progesterone group and 218 for infants in the
      placebo group at 6 months (P = 0.45) and 193 and 194, respectively, at 18 months
      (P = 0.89)). The meta-analysis gave a pooled odds ratio of 1.06 (95% CI, 0.86
      1.31). CONCLUSION: Progesterone treatment did not prevent preterm delivery in
      twin gestations. There were no harmful effects to fetuses and infants of maternal
      progesterone treatment.

PMID- 21739498
TI  - The oligomeric state of the truncated mechanosensitive channel of large
      conductance shows no variance in vivo.
AB  - The mechanosensitive channel of large conductance (MscL) from E. coli serves as
      an emergency release valve allowing the cell to survive acute osmotic downshock.
      It is one of the best studied mechanosensitive channels and serves as a paradigm
      for how a protein can sense and respond to membrane tension. Two MscL crystal
      structures of the orthologs M. tuberculosis and S. aureus have been solved
      showing pentameric and tetrameric structures, respectively. Several studies
      followed to understand whether the discrepancy in their stoichiometry was a
      species difference or a consequence of the protein manipulation for
      crystallization. Two independent studies now agree that the full-length S. aureus
      MscL is actually a pentamer, not tetramer. While detergents appear to play a role
      in modifying the oligomeric state of the protein, a cytoplasmic helical bundle
      has also been implicated. Here, we evaluate the role of the C-terminal region of
      S. aureus MscL in the oligomerization of the channel in native membranes by using
      an in vivo disulfide-trapping technique. We find that the oligomeric state of S.
      aureus MscLs with different C-terminal truncations, including the one used to
      obtain the tetrameric S. aureus MscL crystal structure, are pentamers in vivo.
      Thus, the C-terminal domain of the S. aureus protein only plays a critical role
      in the oligomeric state of the SaMscL protein when it is solubilized in
      detergent.

PMID- 21739499
TI  - Vaginal micronized progesterone and risk of preterm delivery in high-risk twin
      pregnancies: secondary analysis of a placebo-controlled randomized trial and meta
      analysis.
AB  - OBJECTIVES: Progesterone treatment reduces the risk of preterm delivery in high
      risk singleton pregnancies. Our aim was to evaluate the preventive effect of
      vaginal progesterone in high-risk twins. METHODS: This was a subanalysis of a
      Danish-Austrian, double-blind, placebo-controlled, randomized trial (PREDICT
      study), in which women with twin pregnancies were randomized to daily treatment
      with progesterone or placebo pessaries from 20-24 weeks until 34 weeks'
      gestation. This subpopulation consisted of high-risk pregnancies, defined by the
      finding of cervical length <= 10th centile at 20-24 weeks' gestation or history
      of either spontaneous delivery before 34 weeks or miscarriage after 12 weeks.
      Primary outcome was delivery before 34 weeks. Secondary outcomes were
      complications for infants including long-term follow-up by Ages and Stages
      Questionnaire (ASQ) at 6 and 18 months of age. RESULTS: In 72 (10.6%) of the 677
      women participating in the PREDICT study, the pregnancy was considered to be high
      risk, including 47 with cervical length <= 10th centile, 28 with a history of
      preterm delivery or late miscarriage and three fulfilling both criteria. Baseline
      characteristics for progesterone and placebo groups were similar. Mean
      gestational age at delivery did not differ significantly between the two groups
      either in patients with a short cervix (34.3 +/- 4.1 vs. 34.5 +/- 3.0 weeks, P =
      0.87) or in those with a history of preterm delivery or late miscarriage (34.6 +/
      4.2 vs. 35.2 +/- 2.7 weeks, P = 0.62). Similarly, there were no significant
      differences between the treatment groups in maternal or neonatal complications
      and mean ASQ score at 6 and 18 months of age. CONCLUSION: In high-risk twin
      pregnancies, progesterone treatment does not significantly improve outcome.

PMID- 21739500
TI  - Integrating atom-based and residue-based scoring functions for protein-protein
      docking.
AB  - Most scoring functions for protein-protein docking algorithms are either atom
      based or residue-based, with the former being able to produce higher quality
      structures and latter more tolerant to conformational changes upon binding.
      Earlier, we developed the ZRANK algorithm for reranking docking predictions, with
      a scoring function that contained only atom-based terms. Here we combine ZRANK's
      atom-based potentials with five residue-based potentials published by other labs,
      as well as an atom-based potential IFACE that we published after ZRANK. We
      simultaneously optimized the weights for selected combinations of terms in the
      scoring function, using decoys generated with the protein-protein docking
      algorithm ZDOCK. We performed rigorous cross validation of the combinations using
      96 test cases from a docking benchmark. Judged by the integrative success rate of
      making 1000 predictions per complex, addition of IFACE and the best residue-based
      pair potential reduced the number of cases without a correct prediction by 38 and
      27% relative to ZDOCK and ZRANK, respectively. Thus combination of residue-based
      and atom-based potentials into a scoring function can improve performance for
      protein-protein docking. The resulting scoring function is called IRAD
      (integration of residue- and atom-based potentials for docking) and is available
      at http://zlab.umassmed.edu.

PMID- 21739501
TI  - Designed protein mimics of the Ebola virus glycoprotein GP2 alpha-helical bundle:
      stability and pH effects.
AB  - Ebola virus (EboV) belongs to the Filoviridae family of viruses that causes
      severe and fatal hemhorragic fever. Infection by EboV involves fusion between the
      virus and host cell membranes mediated by the envelope glycoprotein GP2 of the
      virus. Similar to the envelope glycoproteins of other viruses, the central
      feature of the GP2 ectodomain postfusion structure is a six-helix bundle formed
      by the protein's N- and C-heptad repeat regions (NHR and CHR, respectively).
      Folding of this six-helix bundle provides the energetic driving force for
      membrane fusion; in other viruses, designed agents that disrupt formation of the
      six-helix bundle act as potent fusion inhibitors. To interrogate determinants of
      EboV GP2-mediated membrane fusion, we designed model proteins that consist of the
      NHR and CHR segments linked by short protein linkers. Circular dichroism and gel
      filtration studies indicate that these proteins adopt stable alpha-helical folds
      consistent with design. Thermal denaturation indicated that the GP2 six-helix
      bundle is highly stable at pH 5.3 (melting temperature, T(m) , of 86.8 +/- 2.0
      degrees C and van't Hoff enthalpy, DeltaH(vH) , of -28.2 +/- 1.0 kcal/mol) and
      comparable in stability to other viral membrane fusion six-helix bundles. We
      found that the stability of our designed alpha-helical bundle proteins was
      dependent on buffering conditions with increasing stability at lower pH. Small pH
      differences (5.3-6.1) had dramatic effects (DeltaT(m) = 37 degrees C) suggesting
      a mechanism for conformational control that is dependent on environmental pH.
      These results suggest a role for low pH in stabilizing six-helix bundle formation
      during the process of GP2-mediated viral membrane fusion.

PMID- 21739502
TI  - Participation of protein sequence termini in crystal contacts.
AB  - The analysis of the crystal packing interactions, in a nonredundant set of high
      resolution and monomeric globular protein crystal structures, shows that the
      residues located at the N- and C-termini of the sequence tend to participate in
      packing interaction more often than expected and that often they interact with
      each other. Since the sequence termini are, in general, conformationally very
      flexible and since they host electrical charges of opposite sign, it can be
      hypothesized that they play a crucial role in the early formation of the
      nonphysiological contacts that bring to protein crystallization. It is thus not
      surprising that modest lengthening/shortening of the sequence termini have often
      a dramatic effect on protein crystallogenesis.

PMID- 21739503
TI  - Extent of enthalpy-entropy compensation in protein-ligand interactions.
AB  - The extent of enthalpy-entropy compensation in protein-ligand interactions has
      long been disputed because negatively correlated enthalpy (DeltaH) and entropy
      (TDeltaS) changes can arise from constraints imposed by experimental and
      analytical procedures as well as through a physical compensation mechanism. To
      distinguish these possibilities, we have created quantitative models of the
      effects of experimental constraints on isothermal titration calorimetry (ITC)
      measurements. These constraints are found to obscure any compensation that may be
      present in common data representations and regression analyses (e.g., in DeltaH
      vs. -TDeltaS plots). However, transforming the thermodynamic data into DeltaDelta
      plots of the differences between all pairs of ligands that bind each protein
      diminishes the influence of experimental constraints and representational bias.
      Statistical analysis of data from 32 diverse proteins shows a significant and
      widespread tendency to compensation. DeltaDeltaH versus DeltaDeltaG plots reveal
      a wide variation in the extent of compensation for different ligand
      modifications. While strong compensation (DeltaDeltaH and -TDeltaDeltaS opposed
      and differing by < 20% in magnitude) is observed for 22% of modifications (twice
      that expected without compensation), 15% of modifications result in reinforcement
      (DeltaDeltaH and -TDeltaDeltaS of the same sign). Because both enthalpy and
      entropy changes arise from changes to the distribution of energy states on
      binding, there is a general theoretical expectation of compensated behavior.
      However, prior theoretical studies have focussed on explaining a stronger
      tendency to compensation than actually found here. These results, showing strong
      but imperfect compensation, will act as a benchmark for future theoretical models
      of the thermodynamic consequences of ligand modification.

PMID- 21739506
TI  - Assessing the RAFT equilibrium constant via model systems: an EPR study.
AB  - Reversible addition-fragmentation chain transfer (RAFT) equilibrium constants,
      K(eq), for the model system cyano-iso-propyl dithiobenzoate (CPDB) - cyano-iso
      propyl radical (CIP) have been deduced via electron paramagnetic resonance (EPR)
      spectroscopy. The CIP species is produced by thermal decomposition of azobis-iso
      butyronitrile (AIBN). In solution of toluene at 70  degrees C, K(eq) has been
      determined to be (9 +/- 1) L . mol(-1). Measurement of K(eq) = k(ad)/k(beta)
      between 60 and 100  degrees C yields DeltaE(a) = (-28 +/- 4) kJ . mol(-1) as the
      difference in the activation energies of k(ad) and k(beta). The data measured on
      the model system are indicative of fast fragmentation of the intermediate radical
      produced by addition of CIP to CPDB.

PMID- 21739507
TI  - Computational design and selections for an engineered, thermostable terpene
      synthase.
AB  - Terpenoids include structurally diverse antibiotics, flavorings, and fragrances.
      Engineering terpene synthases for control over the synthesis of such compounds
      represents a long sought goal. We report computational design, selections, and
      assays of a thermostable mutant of tobacco 5-epi-aristolochene synthase (TEAS)
      for the catalysis of carbocation cyclization reactions at elevated temperatures.
      Selection for thermostability included proteolytic digestion followed by capture
      of intact proteins. Unlike the wild-type enzyme, the mutant TEAS retains
      enzymatic activity at 65 degrees C. The thermostable terpene synthase variant
      denatures above 80 degrees C, approximately twice the temperature of the wild
      type enzyme.

PMID- 21739508
TI  - A double click strategy applied to the reversible polymerization of
      furan/vegetable oil monomers.
AB  - This investigation describes preliminary results related to the preparation of
      monomers based on vegetable oil derivatives bearing furan heterocycles appended
      through thiol-ene click chemistry, and their subsequent polymerization via the
      Diels-Alder (DA) polycondensation between furan and maleimide complementary
      moieties, i.e. a second type of click chemistry. Following the optimization of
      these interactions with model compounds, two basic approaches were considered for
      these DA polymerizations, namely (i) the use of monomers with two terminal furan
      rings in conjunction with bismaleimides (AA + BB systems) and (ii) the use of AB
      monomers incorporating both furan and maleimide end-groups. This ongoing study
      clearly showed that both approaches were successful, albeit with different
      outcomes, in terms of the nature of the products. The application of the retro-DA
      reaction confirmed their thermoreversible character, i.e. the clean-cut return to
      their respective starting monomers. 

PMID- 21739509
TI  - Selective and Sequential Re-Assembly of Patterned Block Copolymer Thin Film for
      Fabricating Polymeric, Inorganic, and Their Composite Nanostructured Arrays.
AB  - We report that the nanostructures of poly(styrene-block-4-vinylpyridine) block
      copolymer (PS-b-P4VP) thin film on a wafer substrate can be re-assembled by
      sequential vapor treatment using selected solvents. Metal or other inorganic
      nanoparticles that were randomly pre-loaded inside or on the surface of PS-b-P4VP
      thin film could be pulled to the rim of PS and P4VP along with the movements of
      PS and P4VP blocks during the treatment. As a result, the patterned polymeric or
      inorganic/polymer composite nanoisland and nanoring arrays were fabricated. 

PMID- 21739510
TI  - Effects of thermal annealing upon the nanomorphology of poly(3-hexylselenophene)
      PCBM blends.
AB  - Grazing incidence X-ray diffraction (GI-XRD) is used to characterize the
      crystallographic dynamics of low molecular weight (LMW) and high molecular weight
      (HMW) poly(3-hexylselenophene) (P3HS) films and blend films of P3HS with [6-6-]
      phenyl-C(61) -butyric acid methyl ester (PCBM) as a function of 'step-by-step'
      thermal annealing, from room temperature to 250  degrees C. The temperature
      dependent GIXRD data show how the melting point of P3HS crystallites is decreased
      by the presence of PCBM. P3HS crystallite domain sizes dramatically increase upon
      annealing to the P3HS melting temperature. The formation of well-oriented HMW
      P3HS crystallites with the (100) plane parallel to the substrate (edge-on
      orientation), when cooled from melt, are observed. We compare the behaviour of
      P3HS pure and blend films with that of poly(3-hexyl)thiophene (P3HT) pure and
      PCBM blended films and suggest that the similar temperature dependent behaviour
      we observe may be a common to polythiophene and related polymers and their
      blends.

PMID- 21739512
TI  - Thyroglobulin-guided (131)I ablation in low-risk differentiated thyroid
      carcinoma: is the yardstick accurate enough?

PMID- 21739514
TI  - EGFR expression in advanced head and neck cutaneous squamous cell carcinoma.
AB  - BACKGROUND: The significance of epidermal growth factor receptor (EGFR)
      expression in advanced cutaneous squamous cell carcinoma (SCC) of the head and
      neck remains poorly understood. METHODS: We performed a retrospective review of
      patients with advanced-stage (stage III or stage IV) cutaneous SCC of the head
      and neck (n = 56). RESULTS: The majority of patients (91%) had stage III disease,
      with 54% having regional metastasis and 9% with distant metastasis. Two-year
      survival was 64% and the 5-year survival was 56%. EGFR was found to be
      overexpressed in 56% of primary tumors and 58% of regional metastatic disease.
      Overall survival did not correlate with EGFR (p = .47) expression in primary
      lesions, nor was it associated with an increase in regional (p = .74) or distant
      metastasis (p = .56). Furthermore, there was no correlation between
      clinicopathologic characteristics and EGFR expression CONCLUSIONS: These data do
      not suggest upregulation of EGFR is associated with poor survival or aggressive
      disease.

PMID- 21739515
TI  - Clinicopathologic analysis and predictive factors for distant metastases in
      patients with head and neck squamous cell carcinomas.
AB  - BACKGROUND: The recognition of patients at high risk for the development of
      distant metastasis (DM) is required to recognize a subset of patients who may
      benefit from systemic therapy. METHODS: In a retrospective analysis of patients
      treated between 1995 and 2006, 443 patients with surgically treated primary head
      and neck squamous cell carcinoma were included. The frequency and
      clinicopathologic risk factors for DM were evaluated. RESULTS: A total of 60
      patients (13.5%) developed DM. In a univariate analysis, tumor site (pharynx), pN
      classification (pN2-N3), differentiation grade (poorly differentiated), disease
      stage (stage IV), number (3 or more nodes), and site (bilateral nodes) of nodal
      metastasis were found to be significantly associated with the risk of DM. In a
      multivariate analysis, the only significant risk factors were the differentiation
      grade and the number and site of nodal metastasis. CONCLUSIONS: Patients with
      pharyngeal poorly differentiated tumors, with multiple or bilateral nodal
      metastases, are at greater risk of DM and should be considered for systemic
      therapy.

PMID- 21739516
TI  - Utility of daily image guidance with intensity-modulated radiotherapy for tumors
      of the base of skull.
AB  - BACKGROUND: This study was carried out to report our experience using intensity
      modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT) for
      tumors involving the base of skull. METHODS: In all, 100 patients were
      prospectively treated with IMRT to a median dose of 64 Gy (range, 45-70 Gy).
      Daily helical megavoltage computed tomography (MVCT) scans were obtained as part
      of an IGRT registration protocol for patient alignment. RESULTS: The 2-year local
      regional control was 91%. A total of 3295 daily MVCT scans were obtained. The
      mean shift to account for interfraction motion was 1.18 +/- 1.75 mm, 1.81 +/-
      1.34 mm, and 1.33 +/- 1.19 mm for the medial-lateral (ML), superior-inferior
      (SI), and anterior-posterior (AP) directions, respectively. Pretreatment shifts
      of >3 mm occurred in 10%, 26%, and 18%, in the ML, SI, and AP directions,
      respectively. CONCLUSIONS: The feasibility and efficacy of daily IGRT as a
      complement to IMRT for skull base were demonstrated.

PMID- 21739517
TI  - Reconstruction of the jejunoesophageal anastomosis with a circular mechanical
      stapler in total laryngopharyngectomy defects.
AB  - BACKGROUND: The aim of this study was to demonstrate the technical feasibility
      and potential benefits of using a circular mechanical stapler with free jejunal
      transfer for jejunoesophageal anastomosis in total laryngopharyngectomy
      reconstruction while comparing the rates of fistula and stricture. METHODS: This
      study was a retrospective review of 12 free jejunal flaps completed with circular
      mechanical stapler for the jejunoesophageal anastomosis with comparison to 17
      jejunal free flaps where all anastomoses were hand sewn. RESULTS: In all, 29
      patients underwent free jejunal transfer: 12 had jejunal free flap with circular
      mechanical stapler for jejunoesophageal anastomosis, whereas 17 patients had hand
      sewn anastomosis. Corresponding rates of fistula and stricture were 0/12 fistulas
      and 3/12 strictures in the stapler cohort and 2/17 fistulas with 0/17 strictures
      in the hand-sewn cohort. No statistically significant difference in rate of
      fistula was observed between each cohort, whereas a trend toward increased rate
      of stricture (p = .06) was observed in the stapled anastomosis cohort.
      CONCLUSIONS: Use of circular mechanical stapler appears to be a safe and
      effective technique at the jejunoesophageal anastomosis for total
      laryngopharyngeal defects with comparable fistula and stricture rates to grafts
      that are hand sewn.

PMID- 21739518
TI  - Secondary tracheoesophageal puncture and myotomy--A novel outpatient technique.
AB  - BACKGROUND: The purpose of this study was to show a novel technique for secondary
      tracheoesophageal puncture (TEP) and myotomy in patients who previously underwent
      total laryngectomy. METHODS: Fifteen patients underwent secondary TEP and 3
      patients underwent myotomy. In 1 patient, both myotomy and TEP were done
      concurrently. A Foley catheter is nasally inserted into the esophagus with the
      patient under local anesthesia and the catheter balloon is inflated at the site
      of the planned procedure. The myotomy is performed over the inflated balloon for
      esophageal posterior wall protection and a voice prosthesis is inserted in a
      small incision made by the physician. When only myotomy is performed, the muscles
      over the mucosa are incised. A voice test is performed immediately. RESULTS: All
      patients exhibited good voice rehabilitation. One patient who had a myotomy had a
      penetration of the pharyngeal mucosa with immediate closure and no sequelae.
      CONCLUSION: Outpatient Foley catheter-guided myotomy and secondary TEP are
      simple, safe, time saving, and cost-effective procedures.

PMID- 21739519
TI  - Improved survival with elective neck dissection in thick early-stage oral
      squamous cell carcinoma.
AB  - BACKGROUND: Management of the node-negative neck in T1 to T2 oral squamous cell
      carcinoma (SCC) remains controversial. The purpose of this study was to determine
      if elective neck dissection improves outcomes in thick primary tumors since this
      reflects current practice in most institutions and has not been specifically
      addressed in the literature. METHODS: Retrospective analysis comparing elective
      neck dissection versus observation in 153 patients with T1 to T2 N0 oral SCC >=4
      mm thick. RESULTS: On multivariable analysis, elective neck dissection was a
      significant predictor of improved regional control (hazard ratio [HR], 0.1; p <
      .001), disease-specific (HR, 0.1; p < .001), and overall survival (HR, 0.3; p =
      .001). Regional failure accounted for 22% of disease-related deaths in the
      elective neck dissection group compared to 92% in the observation arm.
      CONCLUSION: Elective neck dissection is associated with a clinically significant
      survival advantage in thick T1 to T2 oral SCC by reducing the risk of regional
      failure, and we support its routine application in these patients.

PMID- 21739520
TI  - Functional capacity of the thyroid autograft and heterograft: An experimental
      study.
AB  - BACKGROUND: The aim of this study was to investigate the functional capacity of
      thyroid autografts/heterografts in a guinea pig model. METHODS: A total of 24
      guinea pigs were divided into 4 groups. Group A had only a thyroidectomy
      incision, and group B had total thyroidectomy. We performed autotransplantation
      in group C and heterotransplantation in group D. We monitored the guinea pigs for
      an 8-week period, with weekly measurements of free triiodothyronine (fT3), free
      thyroxine (fT4), and thyroid-stimulating hormone (TSH). At the final stage, the
      autografts/heterografts were histologically examined. RESULTS: In group B,
      fT3/fT4 showed a gradual decrease; however, an increase of TSH was noted. In
      groups C and D, fT3/fT4 showed a gradual decrease, followed by a gradual increase
      until euthyroid levels; an exact opposite was noted for TSH. In histologic
      examination, there were functional thyroid follicles in all animals of groups C
      and D. CONCLUSIONS: The autotransplanted/heterotransplanted guinea pig's thyroid
      tissue provides adequate thyroid function.

PMID- 21739521
TI  - Recurrent episodes of asystole from carotid sinus hypersensitivity triggered by
      positioning for head and neck surgery.
AB  - BACKGROUND: We present a case report of a patient with recurrent thyroid
      carcinoma, previously treated with surgery and radiotherapy, who developed
      asystolic episodes on 2 occasions as the result of positioning of the neck in
      hyperextension for head and neck surgery. METHODS AND RESULTS: In carotid sinus
      hypersensitivity (CSH), the carotid sinus reflex is greatly exaggerated,
      resulting in profound bradycardia and asystole. Predisposing risk factors for the
      development of CSH in this patient included history of previously treated head
      and neck cancer and the presence of tight surgical scars. His negative
      cardiovascular history, the time sequence between neck positioning and asystole,
      and the fact that asystole recurred during the second surgery strongly suggest
      that CSH was precipitated by hyperextension of the neck during positioning.
      CONCLUSIONS: A heightened awareness of this syndrome, close monitoring, and
      preparedness for timely diagnosis and management are essential for a successful
      outcome.

PMID- 21739522
TI  - A specific deficit in spatial memory acquisition in post-traumatic stress
      disorder and the role of sleep in its consolidation.
AB  - Posttraumatic stress disorder (PTSD) is characterized by the presence of anatomo
      functional hippocampal alterations. To date, the ability to orient within the
      environment, which relies on hippocampal integrity, has never been investigated
      in PTSD. We hypothesized that the ability to form a cognitive map of the
      environment would be impaired in PTSD. Moreover, spatial memory consolidation
      benefits from postlearning sleep. Because PTSD individuals often complain about
      sleep disturbances, we hypothesized that any sleep effect on memory performance
      would be hampered in these subjects. Twenty-two subjects, all survivors of the
      L'Aquila 2009 earthquake, were divided into a PTSD and a control group, based on
      clinical evaluation. After an acquisition phase, they were tested twice ("test"
      and "retest") on a virtual navigation task. In addition, participants were
      administered the Digit Span and Task Switching. Subjective sleep quality and
      sleep disturbances were also assessed. The two testing sessions were on
      consecutive mornings, interspersed with a night of sleep. During the acquisition
      phase, the PTSD group took more than twice as long to form a cognitive map of the
      environment compared to the control group. However, once this phase was
      successfully completed, the two groups did not differ at test, but they
      tendentially differed at postsleep retest. Additional analyses comparing
      performances between groups on test-retest difference scores confirm that sleep
      dependent consolidation may be differentially affected in the two groups. Our
      findings are strictly confined to the navigation performance, excluding a
      generalized cognitive deficit. PTSD also reported more subjective sleep
      disturbances and shorter sleep time than controls, which were correlated to worse
      performance at retest. The specific deficit in the formation of a cognitive map
      reported in PTSD may be related to hippocampal dysfunctions as well as to the
      sleep disturbances experienced by these patients. The possible deficiency of
      sleep-dependent spatial performance improvement should however be confirmed by
      further studies comprising a wake control group.

PMID- 21739523
TI  - 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked
      exploration and contextual fear conditioning.
AB  - To explore the role of adult hippocampal neurogenesis in novelty processing, we
      assessed novel object recognition (NOR) in mice after neurogenesis was arrested
      using focal x-irradiation of the hippocampus, or a reversible, genetic method in
      which glial fibrillary acidic protein-positive neural progenitor cells are
      ablated with ganciclovir. Arresting neurogenesis did not alter general activity
      or object investigation during four exposures with two constant objects. However,
      when a novel object replaced a constant object, mice with neurogenesis arrested
      by either ablation method showed increased exploration of the novel object when
      compared with control mice. The increased novel object exploration did not
      manifest until 4-6 weeks after x-irradiation or 6 weeks following a genetic
      ablation, indicating that exploration of the novel object is increased
      specifically by the elimination of 4- to 6-week-old adult born neurons. The
      increased novel object exploration was also observed in older mice, which
      exhibited a marked reduction in neurogenesis relative to young mice. Mice with
      neurogenesis arrested by either ablation method were also impaired in one-trial
      contextual fear conditioning (CFC) at 6 weeks but not at 4 weeks following
      ablation, further supporting the idea that 4- to 6-week-old adult born neurons
      are necessary for specific forms of hippocampal-dependent learning, and
      suggesting that the NOR and CFC effects have a common underlying mechanism. These
      data suggest that the transient enhancement of plasticity observed in young adult
      born neurons contributes to cognitive functions.

PMID- 21739524
TI  - Self-efficacy beliefs mediate the relationship between subjective cognitive
      functioning and physical and mental well-being after hematopoietic stem cell
      transplant.
AB  - OBJECTIVE: Cognitive problems are commonly reported by hematopoietic stem cell
      transplant (HSCT) survivors and are associated with poorer physical and mental
      well-being. It was hypothesized that adverse effects of subjective cognitive
      impairment occur because cognitive difficulties reduce survivors' confidence that
      they can manage HSCT-related symptoms-that is, self-efficacy for symptom
      management. METHODS: Hematopoietic stem cell transplant survivors (n = 245), 9
      months to 3 years post-HSCT, completed measures of subjective cognitive
      functioning, self-efficacy for symptom management, and clinically important
      outcomes: depressed mood, anxiety, and quality of life. Mediation analyses using
      bootstrapping were conducted to investigate whether effects of subjective
      cognitive impairment on these outcomes were mediated by self-efficacy for
      cognitive, emotional (SE-Emotional), social (SE-Social), and physical (SE
      Physical) symptom management. RESULTS: Self-efficacy mediated relations between
      subjective cognitive impairment and depressed mood (total indirect effect = 
      0.0064 and 95% CI -0.0097 to -0.0036), anxiety (total indirect effect = -0.0045,
      CI -0.0072 to -0.0021), and quality of life (total indirect effect = 0.0952, CI
      0.0901 to 0.2642). SE-Emotional was a unique mediator when the outcome was
      depressed mood and anxiety. SE-Social, SE-Physical, and SE-Emotional were
      specific mediators when outcome was quality of life. CONCLUSIONS: Findings
      support the conclusion that subjective cognitive impairment reduces HSCT
      survivors' confidence in their ability to manage common post-HSCT symptoms, with
      implications for physical and mental well-being. Interventions that help enhance
      survivors' self-efficacy, particularly self-efficacy for the management of
      emotional symptoms, are likely to benefit HSCT survivors who report subjective
      cognitive impairment.

PMID- 21739525
TI  - Neural mechanisms underlying the grouping effect in short-term memory.
AB  - Dividing auditory sequence into groups, or imposing rhythmic, tonal, or spatial
      structure during presentation, improves recall performance. Several competing
      computational models have been proposed to account for these effects, but little
      is known about the neural correlates of grouping and hence the representations
      that encode grouped sequences. The present study used functional magnetic
      resonance imaging (fMRI) to compare the auditory encoding of grouped and
      ungrouped lists of sub-span (six letters) and supra-span (nine letters) length in
      an immediate serial recall (ISR) task. Analysis of activation revealed an
      extensive premotor and prefrontal network, which was significantly less active
      when short-term memory (STM) span was exceeded during encoding. Only primary
      auditory cortex showed an increase in activation when memory span was exceeded.
      Comparison of activation for grouped and ungrouped lists showed that during the
      subspan phase bilateral planum temporale showed less activation for grouped
      stimuli, while during the supra-span phase supramarginal and inferior parietal
      areas were more active for grouped lists. The magnitude of both temporal and
      parietal activations predicted enhanced recall of grouped lists. Thus neural
      signatures of grouping seem to reflect more structured processing in parietal
      areas instead of reliance on perceptual-auditory processing in temporal regions.

PMID- 21739526
TI  - Cortical thickness is linked to executive functioning in adulthood and aging.
AB  - Executive functions that are dependent upon the frontal-parietal network decline
      considerably during the course of normal aging. To delineate neuroanatomical
      correlates of age-related executive impairment, we investigated the relation
      between cortical thickness and executive functioning in 73 younger (20-32 years)
      and 56 older (60-71 years) healthy adults. Executive functioning was assessed
      using the Wisconsin Card Sorting Test (WCST). Cortical thickness was measured at
      each location of the cortical mantle using surface-based segmentation procedures
      on high-resolution T1-weighted magnetic resonance images. For regions involved in
      WCST performance, such as the lateral prefrontal and parietal cortices, we found
      that thicker cortex was related to higher accuracy. Follow-up ROI-based analyses
      revealed that these associations were stronger in older than in younger adults.
      Moreover, among older adults, high and low performers differed in cortical
      thickness within regions generally linked to WCST performance. Our results
      indicate that the structural cortical correlates of executive functioning largely
      overlap with previously identified functional patterns. We conclude that
      structural preservation of relevant brain regions is associated with higher
      levels of executive performance in old age, and underscore the need to consider
      the heterogeneity of brain aging in relation to cognitive functioning.

PMID- 21739527
TI  - Concise review: expanding roles for hematopoietic cellular therapy and the blood
      transfusion services.
AB  - Hematopoietic stem cells (HSCs) have remained at the forefront of stem cell
      research for the past 50 years, since the therapeutic potential of bone marrow
      transplantation was realized. Uniquely, among stem and progenitor cells, research
      progress has been made in parallel between the laboratory benchtop and hospital
      bedside during this period. Integral to this work has been the role of the
      transfusion medicine services in the collection, storage, and processing of HSCs.
      The next decade promises to bring further developments: with new fields of
      cellular therapies, stem cell vaccination, and stem cell drug testing opening up.
      This article summarizes exciting areas of research concerning the behavior and
      potential clinical applications of HSCs. For the purposes of clarity, we describe
      in turn the trafficking and transfer of HSCs; ex vivo expansion of HSC units from
      different sources; and finally, applications of specifically selected subsets of
      hematopoietic cells and their progeny.

PMID- 21739528
TI  - Hand shape selection in pantomimed grasping: interaction between the dorsal and
      the ventral visual streams and convergence on the ventral premotor area.
AB  - In visually guided grasping, possible hand shapes are computed from the
      geometrical features of the object, while prior knowledge about the object and
      the goal of the action influence both the computation and the selection of the
      hand shape. We investigated the system dynamics of the human brain for the
      pantomiming of grasping with two aspects accentuated. One is object recognition,
      with the use of objects for daily use. The subjects mimed grasping movements
      appropriate for an object presented in a photograph either by precision or power
      grip. The other is the selection of grip hand shape. We manipulated the selection
      demands for the grip hand shape by having the subjects use the same or different
      grip type in the second presentation of the identical object. Effective
      connectivity analysis revealed that the increased selection demands enhance the
      interaction between the anterior intraparietal sulcus (AIP) and posterior
      inferior temporal gyrus (pITG), and drive the converging causal influences from
      the AIP, pITG, and dorsolateral prefrontal cortex to the ventral premotor area
      (PMv). These results suggest that the dorsal and ventral visual areas interact in
      the pantomiming of grasping, while the PMv integrates the neural information of
      different regions to select the hand posture. The present study proposes system
      dynamics in visually guided movement toward meaningful objects, but further
      research is needed to examine if the same dynamics is found also in real
      grasping.

PMID- 21739529
TI  - Pax7 expressing cells contribute to dermal wound repair, regulating scar size
      through a beta-catenin mediated process.
AB  - During skin wound healing, fibroblast-like cells reconstitute the dermal
      compartment of the repaired skin filling the wound gap. A subset of these cells
      are transcriptionally active for beta-catenin/T-cell factor (TCF) signaling
      during the proliferative phase of the repair process, and beta-catenin levels
      control the size of the scar that ultimately forms by regulating the number of
      dermal fibroblasts. Here, we performed cell lineage studies to reveal a source of
      the dermal cells in which beta-catenin signaling is activated during wound
      repair. Using a reporter mouse, we found that cells in the early wound in which
      TCF-dependent transcription is activated express genes involved in muscle
      development. Using mice in which cells express Pax7 (muscle progenitors) or Mck
      (differentiated myocytes) are permanently labeled, we showed that one quarter of
      dermal cells in the healing wound are Pax7 expressing progeny, but none are Mck
      progeny. Removing one allele of beta-catenin in Pax7 expressing progeny resulted
      in a significantly smaller scar size with fewer Pax7 expressing progeny cell
      contributing to wound repair. During wound healing, beta-catenin activation
      causes muscle satellite cells to adopt a fibrotic phenotype and this is a source
      of dermal cells in the repair process.

PMID- 21739530
TI  - Identification of Mycobacterium cosmeticum sp. as a novel colitogenic infectious
      agent in a nonimmunocompromised patient.

PMID- 21739531
TI  - Urinary tract infections in hospitalized inflammatory bowel disease patients: a
      10-year experience.
AB  - BACKGROUND: Cystitis is the most common genitourinary complication in Crohn's
      disease (CD). We assessed the prevalence of and risk factors for urinary tract
      infections (UTI) in inflammatory bowel diseases (IBD). METHODS: Among the 1173
      IBD patients of the "Nancy IBD cohort" seen between January 1, 2000 and December
      31, 2009, 56 hospitalized patients had 76 documented UTI. Prevalence of UTI in
      IBD was calculated using rates of UTI among non-IBD patients hospitalized during
      the same period. The cases were compared to 175 matched IBD patients without UTI
      hospitalized during the same period to identify risk factors for UTI. RESULTS:
      Prevalence of UTI was 4% in IBD patients versus 3.3% in non-IBD patients (P =
      0.1). Prevalence of UTI was 4.5% and 2.1% in ulcerative colitis (UC) and CD
      patients, respectively (P = 0.6). Risk factors for UTI in CD patients were
      perianal disease (odds ratio [OR] = 2.28, 95% confidence interval [CI], 1.06
      4.89; P = 0.04) and colonic disease (OR = 2.42, 95% CI, 1.05-5.58; P = 0.04).
      Male gender (OR = 0.38, 95% CI, 0.17-0.85, P = 0.02) and noncomplicated behavior
      (OR = 0.26, 95% CI, 0.11-0.60, P = 0.002) were protective factors against UTI in
      CD. In UC patients, age over 40 years (OR = 9.59, 95% CI, 1.93-47.74; P = 0.006)
      and disease duration over 11 months (OR = 10.77, 95% CI, 1.68-68.89, P = 0.01)
      were risk factors for UTI. Male gender was negatively associated with UTI (OR =
      0.04, 95% CI, 0.01-0.36, P = 0.00006). CONCLUSIONS: Hospitalized IBD patients are
      not at increased risk of UTI. Risk factors for UTI include perianal disease and
      colonic disease in CD and age and longer disease duration in UC.

PMID- 21739532
TI  - Cesarean section and offspring's risk of inflammatory bowel disease: a national
      cohort study.
AB  - BACKGROUND: Intestinal bacteria have been implicated in the etiology of the
      common inflammatory bowel diseases (IBD) ulcerative colitis and Crohn's disease.
      Because delivery by cesarean section disturbs the normal bacterial colonization
      of the newborn's intestine, we determined the risk of IBD according to mode of
      delivery. METHODS: A register-based national cohort study of 2.1 million Danes
      born 1973-2008. The effect of mode of delivery on IBD incidence in the age-span 0
      35 years was estimated by means of confounder-adjusted incidence rate ratios
      (IRRs) with 95% confidence intervals (CIs) obtained in Poisson regression
      analysis. Information on mode of delivery was obtained from the Danish Medical
      Birth Registry and cases of IBD were identified in the Danish National Patient
      Registry 1977-2008. RESULTS: During 32.6 million person-years of follow-up, a
      total of 8142 persons were diagnosed with IBD before age 36 years. Cesarean
      section was associated with moderately, yet significantly, increased risk of IBD
      at age 0-14 years (IRR 1.29, 95% CI 1.11-1.49), regardless of parental
      disposition to IBD. Assuming causality, an estimated 3.2% of IBD cases before age
      15 years were attributable to cesarean section. CONCLUSIONS: Rates of IBD with
      onset in childhood are moderately increased after birth by cesarean section but
      underlying mechanisms remain unclear. Even if the association is causal, the
      possible impact of increasing cesarean section practices on the overall burden of
      IBD in childhood is small.

PMID- 21739533
TI  - Narcotic use for inflammatory bowel disease and risk factors during
      hospitalization.
AB  - BACKGROUND: Growing evidence demonstrates the adverse effects of narcotics in
      inflammatory bowel disease (IBD). We sought to study the relationship between
      narcotic use, objective measures of disease activity, and other associated
      factors in hospitalized patients with IBD. METHODS: We performed a retrospective
      cohort study of all adult IBD patients admitted to a general medical or surgical
      ward service at a United States tertiary care center over a 1-year period. We
      collected demographic and disease-specific information, inpatient narcotic use,
      and disease activity measurements from endoscopic and radiologic reports.
      Bivariate comparisons were made between characteristics and narcotic use.
      Logistic regression was used to evaluate the independent effects of
      characteristics on narcotic use. RESULTS: A total of 117 IBD patients were
      included. Narcotics were given to 70.1% of hospitalized patients. Factors
      significantly associated with any inpatient narcotic use: Crohn's disease (CD); P
      <= 0.01, duration of IBD, P = 0.02, prior psychiatric diagnosis, P = 0.02,
      outpatient narcotic use, P <= 0.01, current smoking, P <= 0.01, prior IBD
      specific surgery, P < 0.02, and prior IBD / irritable bowel syndrome (IBS)
      diagnosis, P = 0.02. Narcotic use was not significantly associated with disease
      severity on computed tomography (CT) scan or endoscopy. On multivariate analysis,
      smoking (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.21-15.6) and prior
      outpatient narcotic use (OR 5.41, 95% CI 1.54-19.0) were independently associated
      with inpatient narcotic use. CONCLUSIONS: A majority of patients with IBD are
      prescribed narcotics during hospitalization in spite of data on increased
      complications. Risk factors for narcotic use include CD and associated factors
      (disease duration, surgeries), substance abuse (outpatient narcotics and
      smoking), psychiatric diagnoses, and IBD-IBS.

PMID- 21739534
TI  - Dysplasia is more common in the distal than proximal colon in ulcerative colitis
      surveillance.
AB  - BACKGROUND: In patients with long-standing ulcerative colitis (UC), current
      dysplasia surveillance guidelines recommend four-quadrant biopsies every 10 cm
      throughout the colon. However, this may be inefficient if neoplastic lesions are
      localized in particular segments of the colorectum. The aim was to determine
      whether a difference exists in the anatomic distribution of dysplasia discovered
      in UC patients undergoing colonoscopic surveillance. METHODS: From an
      institutional database of over 700 patients with UC who underwent two or more
      surveillance colonoscopies between 1994-2006, we identified all patients with
      flat (endoscopically invisible) low-grade dysplasia (fLGD) or advanced neoplasia
      (colorectal cancer [CRC] or high-grade dysplasia [HGD]). Pathology reports were
      reviewed regarding the anatomic location of all dysplastic lesions. Fisher's
      exact test was used to compare the frequencies of neoplasia among the different
      colonic segments. RESULTS: We identified 103 patients who progressed to any
      neoplasia (fLGD, HGD, or CRC). These patients underwent a total of 396
      colonoscopies. The mean age at first surveillance colonoscopy was 48.6 years,
      with a mean UC disease duration of 18.2 years; 100% had extensive disease. Fifty
      five patients developed advanced neoplasia. The rectosigmoid was found to have a
      significantly greater number of biopsies positive for advanced neoplasia and for
      any neoplasia compared to all other colonic segments (P < 0.0007); 71.2% of all
      advanced neoplasia was in the rectosigmoid. CONCLUSIONS: The majority of
      dysplastic lesions identified in a surveillance program was detected in the
      rectosigmoid. Endoscopists should consider taking a greater percentage of
      biopsies in these segments as opposed to more proximal areas.

PMID- 21739535
TI  - Patient knowledge in inflammatory bowel disease: CCKNOW, how much do they know?

PMID- 21739536
TI  - Cryptosporidiosis masquerading as a Crohn's flare.

PMID- 21739537
TI  - Setting a high threshold for noninferiority: mesalamine and budesonide in Crohn's
      disease.

PMID- 21739538
TI  - Variants of NOD1 and NOD2 genes display opposite associations with familial risk
      of Crohn's disease and anti-saccharomyces cerevisiae antibody levels.
AB  - BACKGROUND: NOD2 is involved in Crohn's disease (CD), but the role of NOD1
      remains unclear. Anti-Saccharomyces cerevisiae antibodies (ASCA) are higher in CD
      patients and some of their relatives. Using family-based analyses we investigated
      the relationships between NOD2 mutations, NOD1 +32656 variant, and both the risk
      of CD and ASCA levels. We compared allelic frequencies between families with
      multiple CD cases (multiplex), those with one case of CD (simplex), and control
      families, searching for a gradient of at risk alleles according to the prevalence
      of the disease among families. METHODS: In all, 93 CD patients, 160 healthy
      relatives from 22 multiplex families, 22 CD patients and 81 healthy relatives
      from 22 simplex families, and 169 subjects from 27 control families were included
      in the study. ASCA levels were determined by enzyme-linked immunosorbent assay.
      NOD1 +32656, NOD2 R702W, G908R, and 1007fs were genotyped by polymerase chain
      reaction / restriction fragment length polymorphism. RESULTS: In family-based
      analyses NOD2 mutations and the NOD1 wildtype allele were associated with CD in
      multiplex families, with a synergetic effect when risk alleles of both genes were
      transmitted. Lower ASCA levels were strongly associated with the NOD1 variant
      allele. Simplex families had a lower frequency of the "at risk" +32656 allele
      than multiplex families. CONCLUSIONS: The +32656 variant was associated with low
      ASCA level and low risk of CD in multiplex families. NOD2 and NOD1 variants
      displayed antagonist effects on the risk of CD and ASCA level. A gradient of
      NOD1, NOD2 at-risk alleles was associated with the variable prevalence of CD in
      families.

PMID- 21739539
TI  - What caused the recent worldwide increase of inflammatory bowel disease: should
      sucralose be added as a suspect?

PMID- 21739540
TI  - Total synthesis of the chlorine-containing hapalindoles K, A, and G.

PMID- 21739541
TI  - Mechanism of multivalent carbohydrate-protein interactions studied by EPR
      spectroscopy.

PMID- 21739542
TI  - Photocontrol of contracting muscle fibers.

PMID- 21739543
TI  - Palladium-catalyzed C-C bond formation to construct 1,4-diketones under mild
      conditions.

PMID- 21739544
TI  - Carboxylation of alkylboranes by N-heterocyclic carbene copper catalysts:
      synthesis of carboxylic acids from terminal alkenes and carbon dioxide.
AB  - Caught in the act: N-Heterocyclic carbene copper(I) complexes (1; IPr=1,3-bis(2,6
      diisopropylphenyl)imidazol-2-ylidene) serve as an excellent catalyst for the
      carboxylation of alkylboranes (2; R=alkyl) with CO(2) to afford a variety of
      functionalized carboxylic acids (3) in high yields. A novel copper
      methoxide/alkylborane adduct (A) and its subsequent CO(2) insertion product (B)
      have been isolated and shown to be true active catalyst species.

PMID- 21739545
TI  - A triarylboron-based fluorescent thermometer: sensitive over a wide temperature
      range.
AB  - Feeling blue: the luminescence of a triarylboron compound has a high quantum
      yield (at least 0.64) over a wide temperature range (-50 to +100  degrees C) and
      changes from green to blue as the temperature is increased. The luminescence
      color was determined by the population of the two distinct excited-state
      conformations-a local excited state (high temperature) and a twisted
      intramolecular charge-transfer state (low temperature).

PMID- 21739546
TI  - The halogen bond and internal dynamics in the molecular complex of CF3Cl and H2O.

PMID- 21739547
TI  - Diastereoselective total synthesis of (+/-)-schindilactone A.

PMID- 21739548
TI  - Ionothermal synthesis and structure analysis of an open-framework zirconium
      phosphate with a high CO2/CH4 adsorption ratio.
AB  - Less is more: an open-framework zirconium phosphate with unusual 7-ring channels
      was synthesized ionothermally from a deep-eutectic solvent. This small-pore
      material displays a CO(2)/CH(4) adsorption ratio (17.3 at 1 bar) that is
      significantly higher than that of typical 8-ring materials, making it highly
      attractive for CO(2)/CH(4) separations.

PMID- 21739549
TI  - Crossing organolithium compounds with organolithium compounds: molecular squares
      and a cage-encapsulating reaction.

PMID- 21739550
TI  - Mechanosynthesis of the metallodrug bismuth subsalicylate from Bi2O3 and
      structure of bismuth salicylate without auxiliary organic ligands.

PMID- 21739551
TI  - Diversity-oriented production of metabolites derived from chorismate and their
      use in organic synthesis.

PMID- 21739552
TI  - Scaffolding catalysts: highly enantioselective desymmetrization reactions.
AB  - Ex-changing places: a highly enantioselective desymmetrization of 1,2-diols has
      been developed in which the catalyst utilizes reversible covalent bonding to the
      substrate to achieve both high selectivity and rate acceleration (see scheme,
      PMP=pentalmethylpiperidine, TBS=tert-butyldimethylsilyl). Induced
      intramolecularity is responsible for the enhanced rate, thus allowing the
      reaction to be performed at room temperature.

PMID- 21739554
TI  - Label-free nondestructive discrimination of colon carcinoma sublines and
      biomolecular insights into their differential Hsp70 expression: DNA/RNA
      nucleobase specific changes.
AB  - Hsp70 is biologically relevant for its chaperon functions. The CX(-) and CX(+)
      sublines, which derive from the parental colon carcinoma CX2 cell line, are
      accordingly very similar. They have been reported to be specifically different
      only in Hsp70 membrane expression, which is associated with immunostimulatory
      effects. CX(-) /CX(+) have been phenotypically characterized by
      immunofluorescence studies and Raman spectroscopy combined with robust clustering
      and multivariate analysis. With the latter we address the potential of overall
      characterization for CX(-) /CX(+) discrimination and gain molecular insights into
      Hsp70 differential expression. Due to their strong resemblance, CX(-) and CX(+)
      show similar mean Raman spectra, which look indiscernible at first.
      Interestingly, their rather protein-dominated Raman spectra reveal, besides
      changes in protein and amino acids, very specific changes in DNA/RNA nucleotides
      involving pyrimidine ring Raman hypochromic effects. Therefore, discriminating
      CX(-) from CX(+) is ultimately achieved based on principal component scores.
      Because CX(-) /CX(+) are associated with the same lipid marker, changes in
      proteins support lipid interactions with regulatory proteins. More importantly,
      changes observed in nucleobases, which are indicative of DNA/RNA-protein binding
      interactions, suggest transcription deregulations as participating precursor
      onsets of different transport mechanisms that lead to Hsp70 differential
      expression and associated phenotypic variation. Besides immunofluorescence, we
      have used Raman spectroscopy combined with multivariate analysis within an
      autologous tumor system for label-free nondestructive cell-subline
      discrimination, and demonstrate, to our knowledge, the first overall phenotypic
      monitoring with insights into Hsp70 differential expression. This might well
      prove to be useful for Raman label-free cell-sorting of the CX(-) /CX(+)
      sublines.

PMID- 21739555
TI  - Measurement of enzymatic activity and specificity of human and avian influenza
      neuraminidases from whole virus by glycoarray and MALDI-TOF mass spectrometry.
AB  - Influenza neuraminidases hydrolyze the ketosidic linkage between N
      acetylneuraminic acid and its adjacent galactose residue in sialosides. This
      enzyme is a tetrameric protein that plays a critical role in the release of
      progeny virions. Several methods have been described for the determination of
      neuraminidase activity, usually based on colorimetric, fluorescent, or
      chemiluminescent detection. However, only a few of these tests allow
      discrimination of the sialyl-linkage specificity (i.e., alpha2-3- versus alpha2-6
      linked sialyllactosides) of the neuraminidase. Herein we report a glycoarray
      based assay and a MALDI-TOF study for assessing the activity and specificity of
      two influenza neuraminidases on whole viruses. The human A(H3N2) and avian
      A(H5N2) neuraminidase activities were investigated. The results from both
      approaches demonstrated that alpha2-3 sialyllactoside was a better substrate than
      alpha2-6 sialyllactoside for both viruses and that H5N2 virus had a lower
      hydrolytic activity than H3N2.

PMID- 21739556
TI  - Transition state of rare event base pair opening probed by threading into looped
      DNA.

PMID- 21739557
TI  - Binding energetics of ferredoxin-NADP+ reductase with ferredoxin and its relation
      to function.
AB  - To obtain insight into the motional features of proteins for enzymatic function,
      we studied binding reactions between ferredoxin-NADP(+) reductase (FNR) and
      ferredoxin (Fd) using isothermal titration calorimetry and NMR-based magnetic
      relaxation and hydrogen/deuterium exchange (HD(ex)). Fd-FNR binding was
      accompanied by endothermic reactions and driven by the entropy gain. Component
      wise analysis of the net entropy change revealed that increases in the
      conformational entropy of the Fd-FNR complex contributed largely to stabilizing
      the complex. Intriguingly, analyses of magnetic relaxation and HD(ex) rates with
      X-ray B factor implied that Fd binding led to both structural stiffening and
      softening of FNR. Enhanced FNR backbone fluctuations suggest favorable
      contributions to the net conformational entropy. Fd-bound FNR further showed that
      relatively large-scale motions of the C terminus, a gatekeeper for interactions
      of NADP(+) (H), were quenched in the closed form, thereby facilitating exit of
      NADP(+) (H). This can provide a first dynamic structure-based explanation for the
      negative cooperativity between Fd and NADP(+) (H) via FNR.

PMID- 21739558
TI  - Mechanistically distinct nonribosomal peptide synthetases assemble the
      structurally related antibiotics viomycin and capreomycin.

PMID- 21739559
TI  - Tight binding of transition-state analogues to a peptidyl-aminoacyl-L/D-isomerase
      from frog skin.

PMID- 21739560
TI  - N-sulfanylethylanilide peptide as a crypto-thioester peptide.

PMID- 21739561
TI  - Peptide-functionalized luminescent iridium complexes for lifetime imaging of
      CXCR4 expression.
AB  - The chemokine receptor 4 (CXCR4) is over-expressed in 23 types of cancer in which
      it plays a role in, among others, the metastatic spread. For this reason it is a
      potential biomarker for the field of diagnostic oncology. The antagonistic Ac
      TZ14011 peptide, which binds to CXCR4, has been conjugated to luminescent iridium
      dyes to allow for CXCR4 visualization. The iridium dyes are cyclometalated
      octahedral iridium(III) 2-phenylpyridine complexes that can be functionalized
      with one, two or three targeting Ac-TZ14011 peptides. Confocal microscopy and
      fluorescence lifetime imaging microscopy (FLIM) showed that the peptide-iridium
      complex conjugates can be used to visualize CXCR4 expression in tumor cells. The
      CXCR4 receptor affinity and specific cell binding of the mono-, di- and trimeric
      peptide derivatives were assessed by using flow cytometry. The three derivatives
      possessed nanomolar receptor affinity and could distinguish between cell lines
      with different CXCR4 expression levels. This yields the first example of a
      neutral iridium(III) complex functionalized with peptides for FLIM-based
      visualization of a cancer associated membrane receptor.

PMID- 21739562
TI  - Kinetics of DNA refolding from longitudinal exchange NMR spectroscopy.

PMID- 21739563
TI  - A demetallation method for IMP-1 metallo-beta-lactamase with restored enzymatic
      activity upon addition of metal ion(s).

PMID- 21739564
TI  - Photoluminescence in rare earth-doped complex hexafluoride phosphors.
AB  - In this study, using a simple combustion process and a wet chemical process,
      fluorides showing intense photoluminescence were prepared and developed as low
      cost phosphors. The prepared phosphors were characterized by photoluminescence
      (PL) techniques. PL emission spectra of the phosphor suggest the presence of
      Eu(3+) as well as Eu(2+) ions in LiMgBF(6):Eu and Li(2) NaBF(6):Eu lattice sites.
      This article summarizes the fundamentals and possible applications of optically
      useful inorganic fluoride with visible photoluminescence of doped Eu(3+) and
      Eu(2+) ions. Our results on LiMgBF(6):Ce and Li(2) NaBF(6):Ce are also reported.

PMID- 21739566
TI  - Highlights of the special imaging issue.

PMID- 21739567
TI  - Imaging diagnosis and staging of hepatocellular carcinoma.

PMID- 21739568
TI  - Monolayers at air-water interfaces: from origins-of-life to nanotechnology.
AB  - The air-water interface presents several interesting features, namely a) a
      molecularly flat environment, b) a boundary region between two phases with
      different dielectric constants, c) permits or promotes dynamic interactions
      within the interface region, and d) a point of interaction between hydrophobic
      compounds and aqueous molecules. Accordingly, Langmuir monolayers at the air
      water interface have several unique characteristics and properties, which require
      investigation. In this review-type personal account, typical examples of
      molecular recognition and molecular patterning at air-water interfaces are first
      introduced, followed by descriptions of specific and unusual properties of
      monolayers on water. In addition, two examples of our own results concerning
      Langmuir monolayers are explained. We have selected examples from two apparently
      unrelated research areas, these being the origin of life and future
      nanotechnology, in order to emphasize the diverse scientific contribution of
      research on monolayers at the air-water interface.

PMID- 21739569
TI  - Contiguous ~16 Mb 1p36 deletion: Dominant features of classical distal 1p36
      monosomy with haplo-lethality.
AB  - Monosomy 1p36 results from heterozygous deletions of the terminal short
      chromosome 1 arm, the most common terminal deletion in humans. The microdeletion
      is split in two usually non-overlapping and clinically distinct classical distal
      and proximal 1p36 monosomy syndromes. Using comparative genome hybridization,
      MLPA and qPCR we identified the largest contiguous ~16 Mb terminal 1p36 deletion
      reported to date. It covers both distal and proximal regions, causes a neonatally
      lethal variant with virtually exclusive features of distal 1p36 monosomy,
      highlighting the key importance of the gene-rich distal region for the "compound"
      1p36 phenotype and a threshold deletion-size effect for haplo-lethality.

PMID- 21739570
TI  - Achondroplasia with synostosis of multiple sutures.
AB  - We report for the second time on a case of achondroplasia with synostosis of
      multiple sutures. The most common mutation for achondroplasia (FGFR3 Gly380Arg,
      resulting in 1138G>A) was identified. Imaging studies disclosed complex
      craniosynostosis and neurosurgical intervention was carried out, particularly for
      posterior plagiocephaly.

PMID- 21739571
TI  - Complex chromosomal rearrangement in a girl with psychomotor-retardation and a de
      novo inversion: inv(2)(p15;q24.2).
AB  - Cytogenetic analysis of DNA from a girl with severe psychomotor retardation
      revealed a de novo pericentric inversion of chromosome 2: 46,XX,inv(2)(p15q24.2).
      In order to elucidate the possible role of the inversion in the girl's abnormal
      phenotype, we analyzed the inversion breakpoints. FISH analysis revealed BAC
      clones spanning the breakpoints at 2p and 2q of the inversion. Southern blot
      hybridization with DNA probes from the BAC regions was used to refine the
      localization of the breakpoints, followed by inverse-PCR which enabled us to
      sequence the inversion breakpoints. We found a complex chromosomal rearrangement,
      including five breakpoints, four at 2q and one at 2p joined with minor
      insertions/deletions of a few bases. The breakpoint at 2p was within the NRXN1
      gene that has previously been associated with autism, intellectual disabilities,
      and psychiatric disorders. In 2q, the breakpoints disrupted two genes, TANC1 and
      RBMS1; the phenotypic effect of these genes is not currently known.

PMID- 21739573
TI  - Bias in patient series with VACTERL association.

PMID- 21739574
TI  - Duplication of the STS region in males is a benign copy-number variant.
AB  - Copy-number variants (CNVs) are a common finding in the human genome, with copy
      gains occurring at a higher frequency than losses in several databases of genomic
      variants in normal individuals. Copy gains of the steroid sulfatase (STS) gene
      have been seen in both males and females. Although deletion of STS in males is
      known to cause X-linked ichthyosis, the clinical significance of STS copy gains
      is less clear, with the duplication reported in individuals with abnormal
      phenotypes and normal relatives. We identified 72 males submitted to our
      laboratory for microarray-based comparative genomic hybridization with
      duplications in the STS region (chrX:6,465,812-8,093,195). In 40 (56%) patients,
      maternal blood was available, and the duplication was found to be inherited from
      the patient's apparently phenotypically normal mother in each of the 40 patients.
      We also identified three females who inherited a duplication of the STS region
      from phenotypically normal fathers, and a phenotypically normal uncle who had the
      same duplication as his nephews. In the remaining cases the inheritance could not
      be confirmed owing to lack of parental samples available for testing. Of the 72
      subjects, 10 (14%) had an additional CNV elsewhere in the genome known to be
      clinically significant and likely causative of the patient's presenting symptoms.
      Based on the frequency with which duplications have been identified in clinically
      normal and abnormal individuals, we suggest a gain of STS in males is a
      population variant and unlikely to be clinically significant.

PMID- 21739575
TI  - Monozygotic twins with variable expression of Van der Woude syndrome.

PMID- 21739576
TI  - Further expansion of the phenotypic spectrum associated with mutations in
      ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS).
AB  - We report on the third case of cutis laxa and progeroid features caused by a
      homozygous mutation in ALDH18A1 that encodes Delta1-pyrroline-5-carboxylate
      synthase (P5CS). This severely affected child, born to consanguineous parents of
      Pakistani origin, presented with lax, wrinkled and thin skin with dilated and
      tortuous subcutaneous blood vessels, corneal clouding, and hypotonia. The child
      had severe global developmental delay and feeding difficulties and died in
      infancy for an unknown reason. The proband was homozygous for a mutation in
      ALDH18A1, c.1923 + 1G > A which results in the production of two anomalous
      transcripts that are predicted to encode proteins lacking the catalytic site for
      the enzyme. The cellular phenotype is characterized by diminished production of
      collagen types I and III, altered elastin ultrastructure, and diminished cell
      proliferation of cultured dermal fibroblasts. This severe clinical and cellular
      phenotype overlaps with a broad group of neurocutaneous syndromes that include
      cutis laxa type II, wrinkly skin syndrome, de Barsy syndrome, and gerodermia
      osteodysplastica. The findings presented here emphasize the pleiotropic
      presentation of this group of conditions and suggest that multiple components of
      the extracellular matrix are perturbed in these disorders.

PMID- 21739577
TI  - Mutational analysis of 12 patients with the phenotype of Ehlers-Danlos syndrome
      type VIB shows no linkage to the zinc transporter gene SLC39A13.

PMID- 21739578
TI  - Five patients with novel overlapping interstitial deletions in 8q22.2q22.3.
AB  - High-resolution microarray technology has facilitated the detection of
      submicroscopic chromosome aberrations and characterization of new microdeletion
      syndromes. We present clinical and molecular data of five patients with
      previously undescribed overlapping interstitial deletions involving 8q22.2q22.3.
      All deletions differ in size and breakpoints. Patients 1-4 carry deletions
      between 5.25 and 6.44 Mb in size, resulting in a minimal deletion overlap of 3.87
      Mb (from 100.69 to 104.56 Mb; hg18) comprising at least 25 genes. These patients
      share similar facial dysmorphisms with blepharophimosis, telecanthus, epicanthus,
      flat malar region, thin upper lip vermillion, down-turned corners of the mouth,
      and a poor facial movement/little facial expression. They have a moderate to
      severe developmental delay (4/4), absent speech (3/4), microcephaly (3/4), a
      history of seizures (3/4), postnatal short stature (2/4), and a diaphragmatic or
      hiatal hernia (2/4). Patient 5 was diagnosed with a smaller deletion of about
      1.92 Mb (containing nine genes) localized within the deletion overlap of the
      other four patients. Patient 5 shows a different facial phenotype and a less
      severe mental retardation. In Patients 1-4, COH1 is involved in the deletion (in
      total or in part), but none of them showed clinical features of Cohen syndrome.
      In two patients (Patients 2 and 4), ZFPM2 (also called FOG2, a candidate gene for
      congenital diaphragmatic hernias) was partly deleted. We suggest that patients
      with a microdeletion of 8q22.2q22.3 may represent a clinically recognizable
      condition characterized particularly by the facial phenotype and developmental
      delay. More patients have to be evaluated to establish a phenotype-genotype
      correlation. (c) 2011 Wiley-Liss, Inc.

PMID- 21739579
TI  - A pigmentary skin defect is a new finding in Marshall-Smith syndrome.
AB  - Marshall-Smith Syndrome (OMIM 602535) was described initially by Marshall in two
      infants with a syndrome characterized by accelerated skeletal maturation, failure
      to thrive, and dysmorphic facial features. We report a new patient with clinical
      features of Marshall-Smith syndrome with additional findings such as
      hyperpigmented lines on trunk and the four extremities. (c) 2011 Wiley-Liss, Inc.

PMID- 21739580
TI  - Trisomy 13 (Patau syndrome) and craniosynostosis.

PMID- 21739581
TI  - A novel nonsense mutation in TUSC3 is responsible for non-syndromic autosomal
      recessive mental retardation in a consanguineous Iranian family.
AB  - The genetic basis of autosomal recessive mental retardation (ARMR) is extremely
      heterogeneous, and there is reason to suspect that the number of underlying gene
      defects may well go beyond 1,000. To date, however, only less than 10 genes have
      been implicated in non-specific/non-syndromic ARMR (NS-ARMR). As part of an
      ongoing systematic study aiming to identify further ARMR genes, we investigated a
      consanguineous family with three patients with NS-ARMR. By linkage analysis and
      subsequent mutation screening we identified a novel nonsense mutation (c.163C > T
      [p.Q55X]) in the second exon of the TUSC3 gene. This is the third MR causing
      defect in TUSC3 to be described and the second independent mutation in this gene
      in a cohort of more than 200 ARMR families from the Iranian population. This
      argues for a more prominent role of TUSC3 in the etiology of this genetically
      heterogeneous disorder as compared to most of the other so far identified ARMR
      genes.

PMID- 21739582
TI  - Genetic and functional analyses identify DISC1 as a novel callosal agenesis
      candidate gene.
AB  - Agenesis of the corpus callosum (AgCC) is a congenital brain malformation that
      occurs in approximately 1:1,000-1:6,000 births. Several syndromes associated with
      AgCC have been traced to single gene mutations; however, the majority of AgCC
      causes remain unidentified. We investigated a mother and two children who all
      shared complete AgCC and a chromosomal deletion at 1q42. We fine mapped this
      deletion and show that it includes Disrupted-in-Schizophrenia 1 (DISC1), a gene
      implicated in schizophrenia and other psychiatric disorders. Furthermore, we
      report a de novo chromosomal deletion at 1q42.13 to q44, which includes DISC1, in
      another individual with AgCC. We resequenced DISC1 in a cohort of 144 well
      characterized AgCC individuals and identified 20 sequence changes, of which 4 are
      rare potentially pathogenic variants. Two of these variants were undetected in
      768 control chromosomes. One of these is a splice site mutation at the 5'
      boundary of exon 11 that dramatically reduces full-length mRNA expression of
      DISC1, but not of shorter forms. We investigated the developmental expression of
      mouse DISC1 and find that it is highly expressed in the embryonic corpus callosum
      at a critical time for callosal formation. Taken together our results suggest a
      significant role for DISC1 in corpus callosum development.

PMID- 21739583
TI  - How high are carrier frequencies of rare recessive syndromes? Contemporary
      estimates for Fanconi Anemia in the United States and Israel.
AB  - For many recessive genetic syndromes, carrier frequencies have been assessed
      through screening studies in founder populations but remain unclear in
      heterogeneous populations. One such syndrome is Fanconi Anemia (FA). FA is a
      model disease in cancer research, yet there are no contemporary data on carrier
      frequency or prevalence in the general United States (US) population or
      elsewhere. We inferred carrier frequency from birth incidence using the Hardy
      Weinberg law. We estimated prevalence using birth incidence and survival data. We
      defined "plausible ranges" to incorporate uncertainty about completeness of case
      ascertainment. We made estimates for the US and Israel using demographic data
      from the Fanconi Anemia Research Fund and Israeli Fanconi Anemia Registry. In the
      US, a plausible range for the carrier frequency is 1:156-1:209 [midpoint 1:181];
      we estimate that 550-975 persons were living with FA in 2010. For Israel, a
      plausible range for the carrier frequency is 1:66-1:128 [midpoint 1:93] in line
      with founder screening studies; we estimate that 40-135 Israelis were living with
      FA in 2008. The estimated US FA carrier frequency of 1:181 is significantly
      higher than the historical estimate of 1:300; hence, the gap may be narrower than
      previously recognized between the US carrier frequency and higher carrier
      frequencies of around 1:100 in several founder groups including Ashkenazi Jews.
      Assessment of cancer risks in heterozygous carriers merits further study.
      Clinical trials in FA will require co-ordination and innovative design because
      the number of living US patients is probably less than 1,000.

PMID- 21739584
TI  - A pilot study to determine whether health care professionals perceive stigma in
      heterozygote carrier identification and disclosure decisions.
AB  - We conducted an empirical pilot study to assess the attitudes of health care
      professionals (HCPs) to the personal identification of heterozygote carrier
      status for two autosomal recessive conditions (cystic fibrosis and a
      hemoglobinopathy) and for an X-linked disorder (Duchenne muscular dystrophy)
      using the Health Orientation Scale (HOS) and a modified HIV Stigma Scale.
      Attitudes towards carrier identification of children were also assessed. Three
      hundred and ten of 742 (42%) eligible HCPs fully or partly completed the survey.
      As measured with the HOS and the modified HIV scale, respondents had a more
      negative reaction to the hypothetical discovery of being a carrier for an
      autosomal recessive genetic condition that was less likely given their self
      identified ancestry. Female respondents had a more negative reaction on both
      scales to being a carrier for an X-linked disorder than men thought their
      partners would feel. However, the differences found on the HOS and modified HIV
      scale are small and their clinical relevance unknown. Fifty-seven percent of
      respondents agreed that parents should tell their children to keep their carrier
      status private with many (44%) agreeing that children who learn that they are
      carriers may suffer from a decrease in self-esteem. The vast majority of
      respondents would inform immediate family members and HCPs of their carrier
      status, but would be unlikely to share this information with neighbors or
      employers. Further study is needed to develop a heterozygote genetic carrier
      stigma scale.

PMID- 21739585
TI  - Fraternal twins with Aarskog-Scott syndrome due to maternal germline mosaicism.
AB  - Aarskog-Scott syndrome is a rare X-linked recessive disorder with characteristic
      facial, skeletal, and genital abnormalities. We report on Aarskog-Scott syndrome
      in male dizygotic twins with an identical de novo mutation in FGD1 that resulted
      from germline mosaicism in the phenotypically normal mother. This is the first
      report of inheritance by germline mosaicism for the FGD1 gene.

PMID- 21739586
TI  - A 1 bp deletion in the dual reading frame deafness gene LRTOMT causes a
      frameshift from the first into the second reading frame.

PMID- 21739587
TI  - Abnormal circadian rhythm of melatonin in Smith-Magenis syndrome patients with
      RAI1 point mutations.

PMID- 21739588
TI  - Successful pregnancy in the patient with Fanconi-Bickel syndrome undergoing daily
      hemodialysis.

PMID- 21739589
TI  - Hyperphosphatasia-mental retardation syndrome due to PIGV mutations: expanded
      clinical spectrum.
AB  - Hyperphosphatasia-mental retardation syndrome is a recently delineated disorder
      associated with a recognizable facial phenotype and brachytelephalangy. This
      autosomal recessive condition is caused by homozygous and compound heterozygous
      missense mutations of PIGV, encoding a member of the GPI-anchor biosynthesis
      pathway. Here, we report on two further, unrelated patients with developmental
      delay, elevated serum levels of AP, distinctive facial features, hypoplastic
      terminal phalanges, anal atresia in one and Hirschsprung disease in the other
      patient. By sequencing PIGV we detected compound heterozygous mutations c.467G>A
      and c.1022C>A in Patient 1 and a homozygous mutation c.1022C>A in Patient 2. We
      reviewed the eight reported cases with proven PIGV mutations and re-defined the
      phenotypic spectrum associated with PIGV mutations: intellectual disability, the
      distinct facial gestalt, brachytelephalangy, and hyperphosphatasia are constant
      features but also anorectal malformations and Hirschsprung disease as well as
      cleft lip/palate and hearing impairment should be considered as part of the
      clinical spectrum. Moreover, seizures and muscular hypotonia are frequently
      associated with PIGV mutations.

PMID- 21739590
TI  - Discovery of genetic susceptibility factors for human birth defects: an
      opportunity for a National Agenda.
AB  - A recent workshop highlighted the current challenges and new opportunities for
      studying the role of genetic factors in the etiology of human birth defects. The
      workshop provided a series of recommendations pertaining to the use of animal
      models, key elements of population-based designs, the need for national
      collaborative projects, biorepositories, and consortia, investigation of new
      types of structural genetic variants, examination of gene-exposure interactions,
      and a strategy for gene variant discovery. A key reason to hold the recent
      workshop and contribute this concise communication to the literature is to draw
      attention to and initiate action toward advancing discoveries about the genetic
      etiologies of birth defects.

PMID- 21739591
TI  - Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel
      placental findings.
AB  - Uniparental disomy (UPD) is defined by the inheritance of both copies of a
      chromosome pair from one single parent. Although 23 cases of paternal UPD6 have
      been reported earlier, the occurrence of trisomy 6 rescue with paternal UPD6 has
      not been previously reported. The phenotype of paternal UPD6 results from
      biallelic expression of the maternally imprinted, paternally expressed ZAC and
      HYMAI genes, and includes transient neonatal diabetes mellitus (TNDM), intra
      uterine growth restriction (IUGR), macroglossia, and minor anomalies. Trisomy
      rescue has been proposed as a pathogenic mechanism leading to UPD of other
      chromosomes. We report on the first case of a prenatally diagnosed infant with
      UPD6 and describe the clinical, cytogenetic, molecular, and novel placental
      findings in a female infant with paternal UPD6. Low-level trisomy 6 and paternal
      UPD6 were prenatally diagnosed through amniocentesis. After birth trisomy 6 was
      documented in the placenta but was not found in three different cell lines from
      the infant. The placenta was small with a peculiar pattern of vascular
      proliferation. Our results of trisomy 6 cells predominantly present in the
      placenta and only in low levels in the amniotic fluid suggest that the
      distribution and proportion of trisomic and diploid UPD cells contribute to the
      variability of fetal and placental phenotypes.

PMID- 21739592
TI  - Constructing "best interests": genetic testing of children in families with
      hypertrophic cardiomyopathy.
AB  - Professional guidelines on genetic testing of children have recently shifted
      their focus from protecting the child's autonomous choice to professionals,
      together with parents, striving to work in the child's "best interest." This
      notion of "best interest" allows room for therapeutical as well as psychological
      and social considerations, and gives rise to the question how parents and
      professionals weigh up the child's best interest in practice. In this qualitative
      study, we followed six extended families involved in genetic testing for
      hypertrophic cardiomyopathy in the Netherlands for 31/2 years. In total 57
      members of these families were interviewed in depth; many of them more than once.
      Our empirical analysis shows that the best interest of a child is constructed via
      long-term processes in the broader context of family and kin. In this context,
      "best interests" are considered and reconsidered. We conclude that a child's best
      interest should not be framed as the result of an instantaneous agreement between
      parents and professionals. In dealing with genetic testing of children, parents
      as well as professionals reflect on and learn from the processes of generating
      new meanings of "best interest." To enable professionals to deal with the variety
      in family life, these learning processes should be documented closely.

PMID- 21739593
TI  - Embracing the unique role of genetic counselors: response to the commentary by
      Madeo et al.

PMID- 21739594
TI  - Revisiting recombinant 8 syndrome.
AB  - Recombinant 8 syndrome, also known as San Luis Valley syndrome, is a rare but
      important cause for developmental delay and chronic illness noted among
      individuals of Hispanic ancestry that occurs with greater reported frequency in
      the Southwest United States. The recombinant chromosome is
      rec(8)dup(8q)inv(8)(p23.1q22.1) and in all known cases is derived by a parental
      pericentric inversion, inv(8)(p23.1q22.1). To test our hypothesis that modern
      medical management strategies may alter the outcome of patients with recombinant
      8 syndrome in regard to mortality, morbidity, and neurodevelopmental outcomes, we
      sought to update the natural history of recombinant 8 syndrome by completing a
      thorough medical and psychological assessment of affected individuals. Twelve
      affected individuals, ranging from 2 to 21 years of age, were recruited with IRB
      approval. Our patients scored on in the mild to severe cognitive functioning
      level (range 30-70), with surprising preservation in the social/adaptive arenas.
      Most patients responded well to heart surgery and developmental outcomes were in
      proportion to cardiac status. Orthopedic surgery to ameliorate effects of
      spasticity can be complicated by long recovery times and decreased ability to
      ambulate. Our findings do not support additional morbidly during cardiac repair.
      Taken together, our findings support a consistent phenotype with improved
      survival in comparison to previously published studies. Efforts to encourage
      learning and developmental progress should not be withheld as quality of life for
      many of these individuals is considered good by their families and medical
      providers.

PMID- 21739595
TI  - A prenatal case of inverted duplication with terminal deletion of 5p not
      including the cat-like cry critical region.

PMID- 21739596
TI  - Rebuttal to the invited comment of Opitz and Carey.

PMID- 21739597
TI  - The FRAXopathies: definition, overview, and update.
AB  - The fragile X syndrome, fragile X tremor ataxia syndrome, and premature ovarian
      insufficiency are conditions related to the X chromosome folate-sensitive fragile
      site FRAXA. Therefore, we propose that they are considered as a family of
      disorders under the general designation of FRAXopathies. The present review will
      outline the main clinical and molecular features of these disorders, with special
      emphasis on the pathogenic mechanisms that lead to distinct phenotypes, starting
      from related mutations. The understanding of these mechanisms is already
      generating promising therapeutic approaches.

PMID- 21739599
TI  - Megacystis, megacolon, and malrotation: a new syndromic association?
AB  - Chronic intestinal pseudo-obstruction (CIPO) can occur as a consequence of
      neuropathies including diffuse Intestinal Neuronal Dysplasia (IND), a relatively
      rare enteric nervous system (ENS) abnormality. Although various authors reported
      of diffuse IND associated either with intestinal malrotation or megacystis, the
      co-existence of these three entities in the same patient has never been described
      before. The aim of this paper is to report for the first time in literature a
      series of patient with such association, focusing on one who carries a de novo
      duplication of chromosome 12, suggesting a new syndromic association (megacolon,
      megacystis, malrotation).

PMID- 21739598
TI  - Down syndrome and dementia: a randomized, controlled trial of antioxidant
      supplementation.
AB  - Individuals with Down syndrome over age 40 years are at risk for developing
      dementia of the Alzheimer type and have evidence for chronic oxidative stress.
      There is a paucity of treatment trials for dementia in Down syndrome in
      comparison to Alzheimer disease in the general (non-Down syndrome) population.
      This 2-year randomized, double-blind, placebo-controlled trial assessed whether
      daily oral antioxidant supplementation (900 IU of alpha-tocopherol, 200 mg of
      ascorbic acid and 600 mg of alpha-lipoic acid) was effective, safe and tolerable
      for 53 individuals with Down syndrome and dementia. The outcome measures
      comprised a battery of neuropsychological assessments administered at baseline
      and every 6 months. Compared to the placebo group, those individuals receiving
      the antioxidant supplement showed neither an improvement in cognitive functioning
      nor a stabilization of cognitive decline. Mean plasma levels of alpha-tocopherol
      increased ~2-fold in the treatment group and were consistently higher than the
      placebo group over the treatment period. Pill counts indicated good compliance
      with the regimen. No serious adverse events attributed to the treatment were
      noted. We conclude that antioxidant supplementation is safe, though ineffective
      as a treatment for dementia in individuals with Down syndrome and Alzheimer type
      dementia. Our findings are similar to studies of antioxidant supplementation in
      Alzheimer disease in the general population. The feasibility of carrying out a
      clinical trial for dementia in Down syndrome is demonstrated.

PMID- 21739600
TI  - Familial intellectual disability and autistic behavior caused by a small FMR2
      gene deletion.
AB  - Alterations of the Fragile Mental Retardation 2 gene (FMR2, synonym AFF2) can
      result in non-specific, mild to borderline X-linked intellectual disability
      (XLID), and behavioral problems. The well-known molecular pathomechanism of this
      condition, also referred to as FRAXE, is a (CCG)(n) trinucleotide repeat
      expansion which leads to silencing of the FMR2 gene. However, deletions within
      the FMR2 gene may also be causative of the disorder. Here, we report on two
      brothers diagnosed with FRAXE in whom a small deletion in the FMR2 gene was
      detected by whole genome array comparative genomic hybridization (CGH). The
      deletion was also present in their clinically healthy mother and maternal uncle
      who was similarly affected, but not in a healthy older brother of the two
      patients. Our observation demonstrates that FMR2 gene deletions may contribute to
      the FRAXE phenotype. Therefore, we suggest that screening for FMR2 gene deletions
      using array CGH should be considered in patients with non-specific XLID and
      absent trinucleotide expansion.

PMID- 21739601
TI  - Colloidally stable silicon nanocrystals with near-infrared photoluminescence for
      biological fluorescence imaging.
AB  - Luminescent silicon nanocrystals (ncSi) are showing great promise as
      photoluminescent tags for biological fluorescence imaging, with size-dependent
      emission that can be tuned into the near-infrared biological window and reported
      lack of toxicity. Here, colloidally stable ncSi with NIR photoluminescence are
      synthesized from (HSiO1.5)n sol-gel glasses and are used in biological
      fluorescence imaging. Modifications to the thermal processing conditions of
      (HSiO1.5)n sol-gel glasses, the development of new ncSi oxide liberation
      chemistry, and an appropriate alkyl surface passivation scheme lead to the
      formation of colloidally stable ncSi with photoluminescence centered at 955 nm.
      Water solubility and biocompatibility are achieved through encapsulation of the
      hydrophobic alkyl-capped ncSi within PEG-terminated solid lipid nanoparticles.
      Their applicability to biological imaging is demonstrated with the in-vitro
      fluorescence labelling of human breast tumor cells.

PMID- 21739602
TI  - Investigation of protein adsorption performance of Ni2+-attached diatomite
      particles embedded in composite monolithic cryogels.
AB  - As a low-cost natural adsorbent, diatomite (DA) (2 MUm) has several advantages
      including high surface area, chemical reactivity, hydrophilicity and lack of
      toxicity. In this study, the protein adsorption performance of supermacroporous
      composite cryogels embedded with Ni(2+)-attached DA particles (Ni(2+)-ADAPs) was
      investigated. Supermacroporous poly(2-hydroxyethyl methacrylate) (PHEMA)-based
      monolithic composite cryogel column embedded with Ni(2+)-ADAPs was prepared by
      radical cryo-copolymerization of 2-hydroxyethyl methacrylate (HEMA) with N,N'
      methylene-bis-acrylamide (MBAAm) as cross-linker directly in a plastic syringe
      for affinity purification of human serum albumin (HSA) both from aqueous
      solutions and human serum. The chemical composition and surface area of DA was
      determined by XRF and BET method, respectively. The characterization of composite
      cryogel was investigated by SEM. The effect of pH, and embedded Ni(2+)-ADAPs
      amount, initial HSA concentration, temperature and flow rate on adsorption were
      studied. The maximum amount of HSA adsorption from aqueous solution at pH 8.0
      phosphate buffer was very high (485.15 mg/g DA). It was observed that HSA could
      be repeatedly adsorbed and desorbed to the embedded Ni(2+)-ADAPs in poly(2
      hydroxyethyl methacrylate) composite cryogel without significant loss of
      adsorption capacity. The efficiency of albumin adsorption from human serum before
      and after albumin adsorption was also investigated with SDS-PAGE analyses.

PMID- 21739603
TI  - Application of thin metal film elements in bioanalysis.
AB  - Advanced metal deposition and microfabrication techniques enable preparation of
      metal surfaces with high precision and excellent control over their size and
      shape with subnanometer resolution. Thin metal films of different types and
      functions can be found in many analytical instruments. Surfaces with high optical
      quality serve as mirrors, beam splitters, antireflective coatings etc. Smooth
      metal coating is crucial in electron microscopy. Unique properties of the thin
      metal films are widely used in optical systems, as tools for sample manipulation
      but also for chemical sensing and detection. While some of the applications are
      widespread and belong to the basic curriculum in analytical chemistry, the newer
      or less common uses of thin metal films are well known only to the experts in the
      field. The purpose of this critical review is to highlight the role of thin metal
      films in bioanalysis and summarize some of their main applications in current
      bioanalytical instrumentation.

PMID- 21739604
TI  - The adhesion molecule NCAM promotes ovarian cancer progression via FGFR
      signalling.
AB  - Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly
      disseminates to organs of the peritoneal cavity, an event mediated by molecular
      mechanisms that remain elusive. Here, we investigated the expression and
      functional role of neural cell adhesion molecule (NCAM), a cell surface
      glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent
      from normal ovarian epithelium but becomes highly expressed in a subset of human
      EOC, in which NCAM expression is associated with high tumour grade, suggesting a
      causal role in cancer aggressiveness. We demonstrate that NCAM stimulates EOC
      cell migration and invasion in vitro and promotes metastatic dissemination in
      mice. This pro-malignant function of NCAM is mediated by its interaction with
      fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is
      required for NCAM-induced EOC cell motility, but targeting the NCAM/FGFR
      interplay with a monoclonal antibody abolishes the metastatic dissemination of
      EOC in mice. Our results point to NCAM-mediated stimulation of FGFR as a novel
      mechanism underlying EOC malignancy and indicate that this interplay may
      represent a valuable therapeutic target.

PMID- 21739605
TI  - Automatic sample preparation of sulfonamide antibiotic residues in chicken breast
      muscle by using dynamic microwave-assisted extraction coupled with solid-phase
      extraction.
AB  - In the work, a rapid, simple and high-throughput sample preparation method was
      developed for the determination of sulfonamide (SA) antibiotic residues in
      chicken breast muscle. The extraction and clean-up were online combined and up to
      20 samples can be treated simultaneously in 6 min. The SAs were first extracted
      with acetonitrile under the action of microwave energy, and then the extract was
      directly introduced into the SPE column for on-line clean-up and concentration.
      Subsequently, the SAs eluted from the SPE column were determined by liquid
      chromatography-tandem mass spectrometry. The precisions of extraction results of
      20 samples were in the range of 4.9-7.4%. The limits of detection and
      quantification obtained were in the range of 2.4-3.6 ng/g and 8.6-11.3 ng/g for
      SAs, respectively. The recoveries of SAs obtained by analyzing chicken muscles at
      three fortified levels (10, 50 and 500 ng/g) were in the range of 82.6-93.2%. The
      results of the validation process prove that the proposed method is suitable for
      treating numbers of complex samples simultaneously in a short time.

PMID- 21739606
TI  - Preparation of metal wire supported solid-phase microextraction fiber coated with
      multi-walled carbon nanotubes.
AB  - Multi-walled carbon nanotubes-coated solid-phase microextraction fiber was
      prepared by a novel protocol involving mussel-adhesive-protein-inspired
      polydopamine film. The polydopamine was used as binding agent to immobilize amine
      functionalized multi-walled carbon nanotubes onto the surface of the stainless
      steel wire via Michael addition or Schiff base reaction. Surface properties of
      the fiber were characterized by field emission scanning electron microscope and X
      ray photoelectron spectroscope. Six phenols in aqueous solution were used as
      model compounds to investigate the extraction performance of the fiber and
      satisfactory results were obtained. Limit of detection was 0.10 MUg/L for 2
      methylphenol (2-MP) and 4-methylphenol (4-MP), and 0.02 MUg/L for 2-ethylphenol
      (2-EP), 4-ethylphenol (4-EP), 2-tert-butylphenol (2-t-BuP), and 4-tert
      butylphenol (4-t-BuP), which were much lower than commercial fiber and fibers
      made in laboratory. RSDs for one unique fiber are in the range of 1.92-7.00%.
      Fiber-to-fiber (n=3) reproducibility ranges from 4.44 to 8.41%. It also showed
      very high stability and durability to acid, alkali, organic solvent, and high
      temperature. Real water sample from Yellow river was applied to test the
      reliability of the established solid-phase microextraction (SPME)-GC method and
      recoveries with addition level at 5 and 100 MUg/L were in the range from 81.5 to
      110.0%.

PMID- 21739607
TI  - Circulating miRNA signature for early diagnosis of lung cancer.

PMID- 21739608
TI  - PD-L1 co-stimulation contributes to ligand-induced T cell receptor down
      modulation on CD8+ T cells.
AB  - T cell receptor (TCR) down-modulation after antigen presentation is a fundamental
      process that regulates TCR signal transduction. Current understanding of this
      process is that intrinsic TCR/CD28 signal transduction leads to TCR down
      modulation. Here, we show that the interaction between programmed cell death 1
      ligand 1 (PD-L1) on dendritic cells (DCs) and programmed death 1 (PD-1) on CD8 T
      cells contributes to ligand-induced TCR down-modulation. We provide evidence that
      this occurs via Casitas B-lymphoma (Cbl)-b E3 ubiquitin ligase up-regulation in
      CD8 T cells. Interference with PD-L1/PD-1 signalling markedly inhibits TCR down
      modulation leading to hyper-activated, proliferative CD8 T cells as assessed in
      vitro and in vivo in an arthritis model. PD-L1 silencing accelerates anti-tumour
      immune responses and strongly potentiates DC anti-tumour capacities, when
      combined with mitogen-activated kinase (MAPK) modulators that promote DC
      activation.

PMID- 21739609
TI  - Phosphine-catalyzed [4+2] annulations of 2-alkylallenoates and olefins: synthesis
      of multisubstituted cyclohexenes.
AB  - From our investigations on phosphine-catalyzed [4+2] annulations between alpha
      alkyl allenoates and activated olefins for the synthesis of cyclohexenes, we
      discovered a hexamethylphosphorous triamide (HMPT)-catalyzed [4+2] reaction
      between alpha-alkyl allenoates 1 and arylidene malonates or arylidene
      cyanoacetates 2 that provides highly functionalized cyclohexenes 3 and 4 in
      synthetically useful yields (30-89%), with moderate to exclusive
      regioselectivity, and reasonable diastereoselectivity. Interestingly, the [4+2]
      annulations between the alpha-alkyl allenoates 1 and the olefins 2 manifested a
      polarity inversion of the 1,4-dipole synthon 1, depending on the structure of the
      olefin, thus providing cyclohexenes 3 exclusively when using arylidene
      cyanoacetates. The polarity inversion of alpha-alkyl allenoates from a 1,4-dipole
      A to B under phosphine catalysis can be explained by an equilibrium between the
      phosphonium dienolate C and the phosphorous ylide D.

PMID- 21739610
TI  - Solubilization of polycyclic aromatics in water by gamma-cyclodextrin
      derivatives.
AB  - A series of hydrophilic per-6-thio-6-deoxy-gamma-cyclodextrins (CDs) were
      synthesized from per-6-iodo-6-deoxy-gamma-CD. These new hosts are able to
      solubilize polycyclic aromatic guests in aqueous solution to much higher extents
      than native CDs. Phase-solubility diagrams were mostly linear in accordance with
      both 1:1 and 1:2 CD-guest complexes in aqueous solution. The stoichiometry of the
      inclusion complexes was further investigated by fluorescence spectroscopy, which
      revealed very pronounced Stokes shifts typical for 1:2 complexes. This finding
      was further consolidated by quantum mechanical calculations of dimer formation of
      the guests and space-filling considerations by using the cross-sectional areas of
      the CDs and guests. The calculated dimerization energies correlated well with the
      binding free energies measured for the 1:2 complexes, and provided the main
      contribution to the driving force of complexation in the gamma-CD cavity.

PMID- 21739611
TI  - Tailored functionalization of carbon nanotubes for electrocatalytic water
      splitting and sustainable energy applications.

PMID- 21739612
TI  - Spontaneous cyclic embryonic movements in humans and guinea pigs.
AB  - Motility assessment before birth can be used to evaluate the integrity of the
      nervous system. Sideways bending (SB) of head and/or rump, the earliest embryonic
      motility in both humans and guinea pigs, can be visualized sonographically. We
      know from other species that early embryonic motility is cyclic. This study
      explores the distribution of SB-to-SB intervals in human and guinea pig embryos
      before the appearance of more complex movements such as general movements. We
      hypothesized that the activity in both species is cyclic. We made 15-min
      sonographic recordings of SBs between 5 weeks and 0 days (5wk0d) and 7wk0d
      conceptional age (CA) in 18 human embryos of uncomplicated IVF pregnancies (term
      38 weeks) and in 20 guinea pig embryos between 3wk4d and 4wk0d CA (term 9 weeks).
      SB-to-SB interval durations were categorized as long (>=10 s) or short (<10 s)
      intervals. For human embryos, the median values for long and short intervals were
      61 s (range, 10-165 s) and 3 s (range, 1-9 s) respectively; for guinea pigs 38 s
      (range, 10-288 s) and 5 s (range, 1-9 s), respectively. During development, the
      duration of long intervals decreased while the number of short intervals
      increased for both species. The earliest embryonic motility in the human and
      guinea pig is performed cyclically with distinct developmental milestones. The
      resemblance of their interval development offers promising possibilities to use
      the guinea pig as a noninvasive animal model of external influences on motor and
      neural development.

PMID- 21739613
TI  - Extracellular matrix functions during neuronal migration and lamination in the
      mammalian central nervous system.
AB  - Extracellular matrix (ECM) glycoproteins are expressed in the central nervous
      system (CNS) in complex and developmentally regulated patterns. The ECM provides
      a number of critical functions in the CNS, contributing both to the overall
      structural organization of the CNS and to control of individual cells. At the
      cellular level, the ECM affects its functions by a wide range of mechanisms,
      including providing structural support to cells, regulating the activity of
      second messenger systems, and controlling the distribution and local
      concentration of growth and differentiation factors. Perhaps the most well known
      role of the ECM is as a substrate on which motile cells can migrate. Genetic,
      cell biological, and biochemical studies provide strong evidence that ECM
      glycoproteins such as laminins, tenascins, and proteoglycans control neuronal
      migration and positioning in several regions of the developing and adult brain.
      Recent findings have also shed important new insights into the cellular and
      molecular mechanisms by which reelin regulates migration. Here we will summarize
      these findings, emphasizing the emerging concept that ECM glycoproteins promote
      different modes of neuronal migration such as radial, tangential, and chain
      migration. We also discuss several studies demonstrating that mutations in ECM
      glycoproteins can alter neuronal positioning by cell nonautonomous mechanisms
      that secondarily affect migrating neurons.

PMID- 21739614
TI  - Biophysics of substrate interaction: influence on neural motility,
      differentiation, and repair.
AB  - The identity and behavior of a cell is shaped by the molecular and mechanical
      composition of its surroundings. Molecular cues have firmly established roles in
      guiding both neuronal fate decisions and the migration of cells and axons.
      However, there is growing evidence that topographical and rigidity cues in the
      extracellular environment act synergistically with these molecular cues. Like
      chemical cues, physical factors do not elicit a fixed response, but rather one
      that depends on the sensory makeup of the cell. Moreover, from developmental
      studies and the plasticity of neural tissue, it is evident that there is dynamic
      feedback between physical and chemical factors to produce the final morphology.
      Here, we focus on our current understanding of how these physical cues shape
      cellular differentiation and migration, and discuss their relevance to repairing
      the injured nervous system.

PMID- 21739615
TI  - Intrinsic properties guide proximal abducens and oculomotor nerve outgrowth in
      avian embryos.
AB  - Proper movement of the vertebrate eye requires the formation of precisely
      patterned axonal connections linking cranial somatic motoneurons, located at
      defined positions in the ventral midbrain and hindbrain, with extraocular
      muscles. The aim of this research was to assess the relative contributions of
      intrinsic, population-specific properties and extrinsic, outgrowth site-specific
      cues during the early stages of abducens and oculomotor nerve development in
      avian embryos. This was accomplished by surgically transposing midbrain and
      caudal hindbrain segments, which had been pre-labeled by electroporation with an
      EGFP construct. Graft-derived EGFP+ oculomotor axons entering a hindbrain
      microenvironment often mimicked an abducens initial pathway and coursed
      cranially. Similarly, some EGFP+ abducens axons entering a midbrain
      microenvironment mimicked an oculomotor initial pathway and coursed ventrally.
      Many but not all of these axons subsequently projected to extraocular muscles
      that they would not normally innervate. Strikingly, EGFP+ axons also took initial
      paths atypical for their new location. Upon exiting from a hindbrain position,
      most EGFP+ oculomotor axons actually coursed ventrally and joined host
      branchiomotor nerves, whose neurons share molecular features with oculomotor
      neurons. Similarly, upon exiting from a midbrain position, some EGFP+ abducens
      axons turned caudally, elongated parallel to the brainstem, and contacted the
      lateral rectus muscle, their originally correct target. These data reveal an
      interplay between intrinsic properties that are unique to oculomotor and abducens
      populations and shared ability to recognize and respond to extrinsic directional
      cues. The former play a prominent role in initial pathway choices, whereas the
      latter appear more instructive during subsequent directional choices.

PMID- 21739616
TI  - BZP and New Zealand's alternative approach to prohibition. [An interview with
      Matt Bowden by Paul Trevorrow].

PMID- 21739617
TI  - Role of the MAGUK protein family in synapse formation and function.
AB  - Synaptic function is crucially dependent on the spatial organization of the
      presynaptic and postsynaptic apparatuses and the juxtaposition of both membrane
      compartments. This precise arrangement is achieved by a protein network at the
      submembrane region of each cell that is built around scaffold proteins. The
      membrane-associated guanylate kinase (MAGUK) family of proteins is a widely
      expressed and well-conserved group of proteins that plays an essential role in
      the formation and regulation of this scaffolding. Here, we review general
      features of this protein family, focusing on the discs large and
      calcium/calmodulin-dependent serine protein kinase subfamilies of MAGUKs in the
      formation, function, and plasticity of synapses.

PMID- 21739618
TI  - Anti-Ro/SSA-associated corrected QT interval prolongation in adults: the role of
      antibody level and specificity.
AB  - OBJECTIVE: Recent evidence suggests that anti-Ro/SSA antibodies, strongly
      associated with the development of congenital heart block, may also be
      arrhythmogenic for the adult heart. In fact, anti-Ro/SSA-positive patients with
      connective tissue disease (CTD) frequently display corrected QT (QTc)
      prolongation associated with an increase in ventricular arrhythmias. However, QTc
      prolongation prevalence markedly differs throughout the studies (10-60%), but the
      reason why is not yet clear. The aim of this study was to evaluate whether anti
      Ro/SSA-associated QTc prolongation in adult patients with CTD is related to
      antibody level and specificity. METHODS: Forty-nine adult patients with CTD
      underwent a resting 12-lead electrocardiogram recording to measure QTc interval,
      and a venous withdrawal to determine anti-Ro/SSA antibody level and specificity
      (anti-Ro/SSA 52 kd and anti-Ro/SSA 60 kd) by immunoenzymatic methods and Western
      blotting. RESULTS: In our population, a direct correlation was demonstrated
      between anti-Ro/SSA 52-kd level and QTc duration (r = 0.38, P = 0.007), patients
      with a prolonged QTc had higher levels of anti-Ro/SSA 52 kd with respect to those
      with a normal QTc (P = 0.003), and patients with a moderate to high level (>=50
      units/ml) of anti-Ro/SSA 52 kd showed a longer QTc interval (P = 0.008) and a
      higher QTc prolongation prevalence (P = 0.008) than those with a low
      positive/negative level (<50 units/ml). On the contrary, no association was found
      between QTc and anti-Ro/SSA 60-kd level. CONCLUSION: In anti-Ro/SSA-positive
      adult patients with CTD, the occurrence of QTc prolongation seems strictly
      dependent on the anti-Ro/SSA 52-kd level. This finding, possibly explaining the
      different QTc prolongation prevalence reported, strengthens the hypothesis that
      an extremely specific autoimmune cross-reaction is responsible for the anti
      Ro/SSA-dependent interference on ventricular repolarization.

PMID- 21739619
TI  - Prospective study of self-reported pain, radiographic osteoarthritis, sarcopenia
      progression, and falls risk in community-dwelling older adults.
AB  - OBJECTIVE: To examine the potential role of self-reported joint pain, stiffness,
      and dysfunction, and radiographic osteoarthritis (ROA), in sarcopenia progression
      and falls risk in older adults. METHODS: Seven hundred nine older adults (50%
      women, mean +/- SD age 62 +/- 7 years) were examined at baseline and followup
      (mean +/- SD 2.6 +/- 0.4 years). ROA was assessed using the Altman atlas, and
      pain at 7 anatomic sites was self-reported. Dual x-ray absorptiometry assessed
      leg lean mass, dynamometry assessed knee extension and whole leg strength, leg
      muscle quality (LMQ) was calculated as whole leg strength relative to leg lean
      mass, and the Physiological Profile Assessment assessed falls risk. RESULTS: In
      women only, baseline knee pain predicted a greater decline in knee extension
      strength, whole leg strength, and LMQ, and a greater increase in falls risk.
      Severe knee pain, stiffness, and dysfunction predicted greater declines in knee
      extension strength and increases in falls risk (all P < 0.05). Hip pain also
      predicted a greater decline in knee extension strength (-1.53 kg; 95% confidence
      interval [95% CI] -2.95, -0.11). No associations were observed between pain and
      sarcopenia indicators in men. Somewhat surprisingly, higher baseline total knee
      ROA score predicted a greater increase in mean leg lean mass (0.05 kg; 95% CI
      0.02, 0.08) in both sexes. A path analysis demonstrated that knee ROA may
      contribute to declines in LMQ in women, through increases in pain, stiffness, and
      dysfunction. CONCLUSION: Knee and hip pain may directly contribute to the
      progression of sarcopenia and increased falls risk in older women.

PMID- 21739620
TI  - Rheumatologists on the road: a subspecialist's role in caring for the homebound.
AB  - OBJECTIVE: By 2030, the number of permanently homebound individuals in the US
      will increase by 50% to reach 2 million. However, no medicine subspecialty
      consult services exist for this rising subset of the population. This pilot
      program establishes a rheumatology consult service for the Mount Sinai Visiting
      Doctors, the largest primary care academic home visit program in the nation
      serving more than 1,000 patients in New York City. Our service addresses the
      unmet need for homebound patients with rheumatic diseases, and secondarily
      provides an educational opportunity for trainees in community-based rheumatology.
      METHODS: Using an electronic medical record, home-based primary care physicians
      sent consult requests to the Rheumatology Division. Initial assessments were made
      using the Routine Assessment of Patient Index Data 3 (RAPID3) questionnaire.
      RESULTS: Over 12 months, 57 home visits were made: 31 new consults and 26
      followup visits. Reasons for referral included medical management of a known
      connective tissue disease, question of inflammatory arthritis, and procedures.
      The demographics for new consults were as follows: 94% women, 45% Hispanic, and
      80% between ages 60 and 101 years. Thirty-nine percent of patients had rheumatoid
      arthritis. Treatment interventions included addition of a disease-modifying
      antirheumatic drug in 11 patients, 11 procedures, nonpharmacologic management in
      8 patients, and a change in the dose of the existing medication in 5 patients. At
      the initial evaluation, the average RAPID3 scores for patients reflected high
      severity of disease. CONCLUSION: The number of consults and the severity of
      disease seen highlight the importance of a rheumatologist's role in the
      community, especially because the number of homebound patients will dramatically
      increase in the future.

PMID- 21739621
TI  - Does obesity predict knee pain over fourteen years in women, independently of
      radiographic changes?
AB  - OBJECTIVE: To examine longitudinal patterns in body mass index (BMI) over 14
      years and its association with knee pain in the Chingford Study. METHODS: We
      studied a total of 594 women with BMI data from clinic visits at years (Y) 1, 5,
      10, and 15. Knee pain at Y15 was assessed by questionnaire. Associations between
      BMI over 14 years and knee pain at Y15 were examined using logistic regression.
      RESULTS: BMI significantly increased from Y1 to Y15 (P < 0.0005) with medians
      (interquartile ranges) of 24.5 kg/m(2)  (22.5-27.2 kg/m(2) ) and 26.5 kg/m(2) 
      (23.9-30.1 kg/m(2) ), respectively. At Y15, 45.1% of subjects had knee pain. A
      greater BMI at Y1 (odds ratio [OR] 1.34, 95% confidence interval [95% CI] 1.05
      1.69), at Y15 (OR 1.34, 95% CI 1.10-1.61), and change in BMI over 15 years (OR
      1.40, 95% CI 1.00-1.93) were significant predictors of knee pain at Y15 (P <
      0.05). BMI change was associated with bilateral (OR 1.61, 95% CI 1.05-1.76, P =
      0.024) but not unilateral knee pain (OR 1.22, 95% CI 0.73-1.76, P = 0.298). The
      association between BMI change and knee pain was independent of radiographic knee
      osteoarthritis (OA). The strength of association between BMI and knee pain at Y15
      was similar during followup measurements. CONCLUSION: Over 14 years, a higher BMI
      predicts knee pain at Y15 in women, independently of radiographic knee OA. When
      adjusted, the association was significant in bilateral, not unilateral, knee
      pain, suggesting alternative pathologic mechanisms may exist. The longitudinal
      effect of BMI on knee pain at Y15 is equally important at any time point, which
      may assist reducing the population burden of knee pain.

PMID- 21739622
TI  - Application of image analysis in the fungal fermentation of Trichoderma reesei
      RUT-C30.
AB  - Trichoderma reesei was grown in a stirred-tank bioreactor (STB) and a
      reciprocating plate bioreactor (RPB) at four different agitation speeds. A
      semiautomatic image analysis protocol that was developed to characterize the
      mycelium morphology during the fermentation process based on four morphological
      types (unbranched, branched, entangled, and clumped microorganisms) was applied
      to study the effect of agitation on the morphology of T. reesei. It was shown via
      statistical validation that broth samples used for image analysis represented the
      whole population of the fungi in the bioreactor. High shear was found to be
      damaging to T. reesei grown in the STB. The gentler shear produced in the RPB was
      not detrimental to the microorganism even at higher agitation speed. Better
      productivity was obtained for T. reesei grown in the STB and the highest
      productivity, 0.121 IU/mL h, was obtained at 400 rpm. The morphological
      parameter, the hyphal growth unit, was found to be correlated to the
      productivity. Understanding the effect of agitation on the morphology and
      productivity of T. reesei could lead to the design of better bioreactors and the
      selection of operating conditions of bioreactors to optimize the production of
      cellulase.

PMID- 21739623
TI  - Making inferences about speciation using sophisticated statistical genetics
      methods: look before you leap.
AB  - Understanding speciation is a fundamental aim of evolutionary biology and a very
      challenging one. Speciation can be viewed as the dynamics of genetic
      differentiation between populations resulting in substantial reproductive
      isolation (Gavrilets 2003). It was generally accepted that very small levels of
      migration prevent genetic differentiation among populations and, therefore,
      speciation. However, recent theoretical work showed that sympatric speciation is
      possible (Gavrilets 2003). Nevertheless, providing empirical evidence that gene
      flow occurred during speciation is challenging because several gene flow
      scenarios can explain observed patterns of genetic differentiation. Positive
      migration rate estimates alone do not prove ongoing gene flow during divergence.
      We also need to know whether migration took place before, during or after
      speciation. There is no statistical method specifically aimed at estimating gene
      flow timing, but several studies used the isolation with migration model (Hey &
      Nielsen 2004, 2007; Hey 2010b) to estimate this parameter and make inferences
      about speciation scenarios. It is tempting to use statistical methods to estimate
      important evolutionary parameters even if they do not appear explicitly in the
      inference model. Nevertheless, before doing so, we need to determine whether they
      can provide reliable results. In this issue of Molecular Ecology, Strasburg and
      Rieseberg (2011) present a simulation study that examines the degree to which
      gene flow timing estimates obtained from IMa2 (Hey 2010b) can be used to make
      inferences about speciation mode. Their results are sobering; gene flow timing
      estimates obtained in this way are not reliable and cannot be used to
      unequivocally establish if gene flow was ongoing during speciation.

PMID- 21739624
TI  - Towards a quantitative description of landscape, demography and flowering
      phenology effects on realized hybridization potential.
AB  - In chemistry, the law of mass action describes how variations in the
      concentrations of chemical compounds lead to different chemical reaction
      outcomes. Does the extent of hybridization, or more particularly, the formation
      of hybrid offspring, likewise depend on the local abundance of pollen from
      compatible species in systems as complex as tall trees which depend on (insect)
      pollinators? In this issue of Molecular Ecology, Field et al. (2011a) present a
      study involving two ecologically divergent eucalypt species. By comparing several
      contrasting settings with different local densities and geographical arrangements
      of adult trees and by studying parentage in progeny arrays, they show that on top
      of pre-mating barriers like flowering time differences, local demography and
      varying scales of pollen dispersal, which in themselves depend on pollinator
      behaviour in reaction to flowering abundance, all interact in a somewhat
      predictable way. In other words, these factors can explain some of the variation
      in hybrid formation observed. In this way, the study introduces important
      progress towards a quantitative description of hybridization potential.
      Therefore, let me tell you about the birds and the bees and the flowers and the
      trees (Newman 1964).

PMID- 21739625
TI  - Increasing evidence of the role of gene flow in animal evolution: hybrid
      speciation in the yellow-rumped warbler complex.
AB  - In this issue of Molecular Ecology, Brelsford et al. (2011) present strong
      evidence for a case of hybrid speciation within the yellow-rumped warbler
      complex. Although homoploid hybrid speciation has now been documented in many
      animals (Mallet 2007), it seems rare in tetrapods (Mavarez & Linares 2008) and it
      has barely even been mentioned in birds (Price 2008). Brelsford and colleagues
      thus present the first detailed molecular evidence suggesting that hybrid
      speciation can occur in birds. Brelsford et al. (2011) posit that Audubon's
      warbler (Dendroica auduboni) constitutes a hybrid species originating from the
      admixture of two distinct parental lineages, represented today by myrtle warbler
      (D. coronata) and black-fronted warbler (D. nigrifrons). The authors present
      three major lines of molecular evidence suggesting that this is not simply a case
      of a hybrid swarm or limited introgression.

PMID- 21739626
TI  - Abstracts of the British Association of Dermatologists 91st Annual Meeting. July
      5-7, 2011. London, United Kingdom.

PMID- 21739627
TI  - Abstracts of Ghent Pathology 2011, the 6th Joint Meeting of the British Division
      of the International Academy of Pathology and the Pathological Society of Great
      Britain & Ireland. May 1013, 2011. Ghent, Belgium.

PMID- 21739628
TI  - Abstracts of the Triological Society Combined Sections Meeting. January 27-29,
      2011. Scottsdale, Arizona, USA.

PMID- 21739629
TI  - A one-star doc responds.

PMID- 21739630
TI  - H1N1 and vaccination of rheumatology patients.

PMID- 21739631
TI  - Are enrolled nurses being misled?

PMID- 21739632
TI  - Role of LMC midwives not mentioned.

PMID- 21739634
TI  - Evidence-base practice disregarded.

PMID- 21739633
TI  - Bullying a serious health hazard.

PMID- 21739635
TI  - Let's have more open discussion.

PMID- 21739636
TI  - Research.  Couples counseling effective way to prevent transmission in Africa.

PMID- 21739637
TI  - SSI. Daily activities conflict with testimony that pain is disabling.

PMID- 21739638
TI  - Prisons.  Denial of HIV drugs may have been retaliation for complaint.

PMID- 21739639
TI  - [Arteriolosclerosis and atherosclerosis. Pathology of the distal and proximal
      arterial bed. Pathogenesis of diabetic microangiopathy].
AB  - Microangiopathy (MAP) in the distal arterial bed develops in the structures high
      in pericytes that have myofibrils and, by interacting with the endothelium, form
      the first peristaltic pumps; they push lymph, hemolymph and blood from the
      arterial bed to the venous one. The role of glucose, hyperglycemia, a glycation
      reaction and its end products in microvascular interstitial tissue damage in the
      arterial bed is shown only in the neuron axon terminals that surround the pool of
      the intercellular medium while the other axonal parts are present in the
      cerebrospinal fluid pool where hyperglycemia is absent. When glucose metabolism
      is activated through the poliolovic pathway, the endothelial cytosole accumulates
      organic osmolytes, such as sorbitol alcohol that, by causing hyperhydration,
      increases the height of endothelial cells. The decreased lumen of arterioles and
      capillaries enhances peripheral resistance to blood flow to give rise
      hypoperfusion and chronic hypoxia. Moreover, by bypassing the exchange
      capillaries and worsening cellular hypoperfusion and hypoxia in the paracrine
      communities, the arteriolo-venular shunt that releases blood into the venous bed
      functions, by getting around the exchange capillaries. Glucose metabolism
      activation through the hexosamine pathway generates glycotoxins, such as glyoxal
      and methylglyoxal. As bifunctional reagents, they interact with proteins
      simultaneously, by using both ends, form cross-links between the collagen fibers
      in the vascular interstitial matrix and irreversibly enhance the rigidity of
      arteriolar and capillary walls. As the rigidity of the walls is increased, the
      pericytes are unable to move blood along the capillaries, by worsening
      hypoperfusion and hypoxia. In diabetes, hyperglycemia becomes persistent and
      glycation increased. The conversion of collagen structured in the vascular wall
      to glycosylation end products and the impaired biological function of endoecology
      are a cause of a biological reaction of interstitial tissue inflammation. The
      obligate part of the biological reaction of inflammation is the oxidation by
      reactive oxygen species and the generation of malondialdehyde, that is also a
      bifunctional reagent. Fibroblast proliferation and arteriosclerosis are a result
      of MAP as a destructive inflammatory process in the arteriolar and capillary
      walls.

PMID- 21739640
TI  - [Experience in using the LABType SSO reagent kits in the practice of a HLA typing
      laboratory].
AB  - HLA was typed from HLA-A, HLA-B, HLA-DRB1 loci (to the second place) in 443
      patients, by applying the LABType SSO reagent kits (One Lambda, USA). The
      findings were analyzed using the software Arlequin version 3.1. There were no
      deviations from the Hardy-Weinberg law. Overall, the authors identified 16, 27,
      and 13 allelic variants ofHLA-A, HLA-B, and HLA-DRB1 loci, respectively. There
      were also 4 most common haplotypes of HLA-A-B-DRBII: HLA-A *03-B*35-DRB1 *01
      (4.29%), HLA-A *01-B*08-DRBl *03 (3.5%), HLA-A*03-B*07-DRBI *15 (3.37%), and HLA
      A *02-B*07-DRBI *15 (2.93%).

PMID- 21739641
TI  - [Abstracts of the Society of French Pediatrics. May 11-14, 2011. Marseille,
      France].

PMID- 21739642
TI  - Maximal sterile barrier precautions do not reduce catheter-related bloodstream
      infections in general surgery units.

PMID- 21739643
TI  - Japan's slow recovery.

PMID- 21739644
TI  - Global food crisis takes heavy toll on east Africa.

PMID- 21739645
TI  - Arabic roots of modern medicine.

PMID- 21739646
TI  - Ignac Semmelweis-celebrating a flawed pioneer of patient safety.

PMID- 21739647
TI  - Sorting through the evidence of adult pneumatosis intestinalis as a harbinger for
      disaster vs benign disease.

PMID- 21739648
TI  - How many criteria does it take to remove a single parathyroid gland?

PMID- 21739649
TI  - The palliative care triangle: a strategy to help make difficult surgical
      decisions.

PMID- 21739650
TI  - Modern day bloodletting: is that laboratory test necessary?

PMID- 21739651
TI  - Abdominal gunshot wounds: not yet ready for implementation.

PMID- 21739652
TI  - Incidentally, it's still cancer.

PMID- 21739653
TI  - Rectal cancer: the good, the bad, and the ugly.

PMID- 21739654
TI  - Enhanced recovery programs: major benefits demonstrated again.

PMID- 21739655
TI  - Surprise, surprise!: more surgery in rural areas than in cities.

PMID- 21739656
TI  - Mortality in the elderly.

PMID- 21739657
TI  - Choosing "The best".

PMID- 21739658
TI  - Pancreatic infections.

PMID- 21739659
TI  - Teaching a new dog old tricks.

PMID- 21739660
TI  - Decreased serum BDNF levels in patients with epileptic and  psychogenic
      nonepileptic seizures.

PMID- 21739661
TI  - Violence against women. Editor's introduction.

PMID- 21739662
TI  - Post-infarct ventricular thrombus: a critical diagnosis made by cardiac magnetic
      resonance imaging.

PMID- 21739663
TI  - Solitary pulmonary mass in mitral valve disease.

PMID- 21739664
TI  - Improving glucose metabolism with resveratrol in a swine model of metabolic
      syndrome through alteration of signaling pathways in the liver and skeletal
      muscle.
AB  - HYPOTHESIS: We hypothesized that supplemental resveratrol would affect glucose
      metabolism in the skeletal muscle and liver to improve blood glucose control.
      DESIGN: Case-control study. SETTING: Hospital laboratory. SUBJECTS: Yorkshire
      miniswine. INTERVENTION: The swine developed metabolic syndrome by consuming a
      high-calorie, high-fat/cholesterol diet for 11 weeks. Pigs were fed either a
      normal diet (control) (n = 7), a hypercholesterolemic diet (HCC) (n = 7), or a
      hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d) (HCRV) (n =
      7). Animals underwent dextrose challenge prior to euthanasia and tissue
      collection. MAIN OUTCOME MEASURES: Measurements of glucose and insulin levels,
      skeletal muscle and liver protein expression, and liver function test results.
      RESULTS: The HCC group had significantly increased blood glucose levels at 30
      minutes as compared with the control and HCRV groups. The HCC group demonstrated
      increased fasting serum insulin levels and levels of aspartate aminotransferase,
      alanine aminotransferase, and alkaline phosphatase. Oil red O staining
      demonstrated increased lipid deposition in the livers of the HCC animals.
      Immunoblotting in the liver showed increased levels of mammalian target of
      rapamycin, insulin receptor substrate 1, and phosphorylated AKT in the HCRV
      group. Immunoblotting in skeletal muscle tissue demonstrated increased glucose
      transporter type 4 (Glut 4), peroxisome proliferating activation receptor
      coactivator 1alpha, peroxisome proliferator-activated receptor alpha, peroxisome
      proliferator-activated receptor , and phosphorylated AKT at threonine 308
      expression as well as decreased retinol binding protein 4 in the HCRV group.
      Immunofluorescence staining for Glut 4 in the skeletal muscle demonstrated
      increased Glut 4 staining in the HCRV group compared with the HCC or control
      groups. CONCLUSION: Supplemental resveratrol positively influences glucose
      metabolism pathways in the liver and skeletal muscle and leads to improved
      glucose control in a swine model of metabolic syndrome.

PMID- 21739667
TI  - Mentoring: On the right path.

PMID- 21739668
TI  - Origins of CD4(+) effector and central memory T cells.
AB  - Lineage-committed effector CD4(+) T cells are generated at the peak of the
      primary response and are followed by heterogeneous populations of central and
      effector memory cells. Here we review the evidence that T helper type 1 (T(H)1)
      effector cells survive the contraction phase of the primary response and become
      effector memory cells. We discuss the applicability of this idea to the T(H)2
      cell, T(H)17 helper T cell, follicular helper T cell (T(FH) cell) and induced
      regulatory T cell lineages. We also discuss how central memory cells are formed,
      with an emphasis on the role of B cells in this process.

PMID- 21739669
TI  - Germinal center B and follicular helper  T cells: siblings, cousins or just good
      friends?
AB  - Humoral immunity requires interaction between specialized populations of B cells
      and CD4(+) T cells, called follicular helper T cells (T(FH) cells), in the
      germinal center (GC) to produce memory B cells and long-lived plasma cells.
      Molecular crosstalk between GC B cells and T(FH) cells influences the survival,
      proliferation and differentiation of each cell type. This pairing of GC B cells
      and T(FH) cells also occurs at the transcriptional level as the Bcl-6-IRF4-Blimp
      1 axis, which is crucial for B cell differentiation, is also essential for the
      T(FH) cell identity. Less is known about the memory B cells that arise from the
      GC pool, as they seem to be distinctly 'programmed' on the basis of their antigen
      receptor affinity to enter the long-lived memory pool.

PMID- 21739670
TI  - Normal T cell homeostasis: the conversion of naive cells into memory-phenotype
      cells.
AB  - Weak T cell antigen receptor (TCR) signals from contact with self ligands act in
      synergy with antiapoptotic signals induced by interleukin 7 (IL-7) to promote the
      survival of naive T cells in a resting state. The amount of background TCR
      signaling in naive T cells is set by post-thymic TCR tuning and operates at an
      intensity just below that required to induce entry into the cell cycle.
      Costimulation from higher concentrations of IL-7 and other common gamma-chain
      cytokines can induce T cells to undergo homeostatic proliferation and conversion
      into cells with a memory phenotype; many of these memory phenotype cells may be
      the progeny of cells responding to self antigens. The molecular mechanisms that
      control the conversion of naive resting T cells into memory-phenotype cells TCR
      dependent in normal animals are beginning to be understood.

PMID- 21739671
TI  - Regional and mucosal memory T cells.
AB  - After infection, most antigen-specific memory T cells reside in nonlymphoid
      tissues. Tissue-specific programming during priming leads to directed migration
      of T cells to the appropriate tissue, which promotes the development of tissue
      resident memory in organs such as intestinal mucosa and skin. Mechanisms that
      regulate the retention of tissue-resident memory T cells include transforming
      growth factor-beta (TGF-beta)-mediated induction of the E-cadherin receptor CD103
      and downregulation of the chemokine receptor CCR7. These pathways enhance
      protection in internal organs, such as the nervous system, and in the barrier
      tissues--the mucosa and skin. Memory T cells that reside at these surfaces
      provide a first line of defense against subsequent infection, and defining the
      factors that regulate their development is critical to understanding organ-based
      immunity.

PMID- 21739672
TI  - T cell exhaustion.
AB  - T cell exhaustion is a state of T cell dysfunction that arises during many
      chronic infections and cancer. It is defined by poor effector function, sustained
      expression of inhibitory receptors and a transcriptional state distinct from that
      of functional effector or memory T cells. Exhaustion prevents optimal control of
      infection and tumors. Recently, a clearer picture of the functional and
      phenotypic profile of exhausted T cells has emerged and T cell exhaustion has
      been defined in many experimental and clinical settings. Although the pathways
      involved remain to be fully defined, advances in the molecular delineation of T
      cell exhaustion are clarifying the underlying causes of this state of
      differentiation and also suggest promising therapeutic opportunities.

PMID- 21739674
TI  - The practice of ethics. RNs learn, discuss issues.

PMID- 21739675
TI  - ANA to comment on new rules on accountable care organizations.

PMID- 21739673
TI  - Natural killer cell memory.
AB  - Natural killer (NK) cells are bone marrow-derived granular lymphocytes that have
      a key role in immune defense against viral and bacterial infections and
      malignancies. NK cells are traditionally defined as cells of the innate immune
      response because they lack RAG recombinase-dependent clonal antigen receptors.
      However, evidence suggests that specific subsets of mouse NK cells can
      nevertheless develop long-lived and highly specific memory to a variety of
      antigens. Here we review published evidence of NK cell-mediated, RAG-independent
      adaptive immunity. We also compare and contrast candidate mechanisms for
      mammalian NK cell memory and antigen recognition with other examples of RAG
      independent pathways that generate antigen receptor diversity in non-mammalian
      species and discuss NK cell memory in the context of lymphocyte evolution.

PMID- 21739676
TI  - [New developments also in general medicine. GSK relies on research as well as
      transparent collaboration with physicians (interview by Dirk Einecke, Wolfgang
      van den Bergh, Peter Overbeck and Cornelius Heyer)].

PMID- 21739677
TI  - [Psychological stress caused by chronic illnesses. A sick soul in an ill body].

PMID- 21739678
TI  - Clearing up COPD questions.

PMID- 21739680
TI  - Peptide modified mesoporous silica nanocontainers.
AB  - Here we report a new peptide modified mesoporous silica nanocontainer (PMSN) as a
      novel controlled release system. The peptides are part of a stimuli responsive
      nanovalve and ensure an efficient cellular uptake.

PMID- 21739679
TI  - Immunological mechanisms of vaccination.
AB  - Vaccines represent one of the greatest triumphs of modern medicine. Despite the
      common origins of vaccinology and immunology more than 200 years ago, the two
      disciplines have evolved along such different trajectories that most of the
      highly successful vaccines have been made empirically, with little or no
      immunological insight. Recent advances in innate immunity have offered new
      insights about the mechanisms of vaccine-induced immunity and have facilitated a
      more rational approach to vaccine design. Here we will discuss these advances and
      emerging themes on the immunology of vaccination.

PMID- 21739681
TI  - A hybrid sol-gel synthesis of mesostructured SiC with tunable porosity and its
      application as a support for propane oxidative dehydrogenation.
AB  - Porous silicon carbide (SiC) is of great potential as catalyst support in several
      industrially important reactions because of its unique thermophysical
      characteristics. Previously porous SiC was mostly obtained by a simple sol-gel or
      reactive replica technique which can only produce a material with low or medium
      surface area (< 50 m2 g(-1)). Here we report a new hybrid sol-gel approach to
      synthesize mesostructured SiC with high surface area (151-345 m2 g(-1)) and
      tunable porosity. The synthesis route involves a facile co-condensation of TEOS
      and alkyloxysilane with different alkyl-chain lengths followed by carbothermal
      reduction of the as-prepared alkyloxysilane precursors at 1350  degrees C. The
      resulting materials were investigated by X-ray diffraction, N2 adsorption
      desorption, transmission electron microscopy, scanning electron microscopy, and X
      ray photoelectron spectroscopy. A mechanism for the tailored synthesis of
      mesostructured SiC was tentatively proposed. To demonstrate the catalytic
      application of these materials, vanadia were loaded on the mesostructured SiC
      supports, and their catalytic performance in oxidative dehydrogenation of propane
      was evaluated. Vanadia supported on the mesostructured silicon carbide exhibits
      higher selectivity to propylene than those on conventional supports such as Al2O3
      and SiO2 at the same propane conversion levels, mainly owing to its outstanding
      thermal conductivity which makes contributions to dissipate the heat generated
      from reaction thus alleviating the hot spots effect and over-oxidation of
      propylene.

PMID- 21739682
TI  - Debridement and wound biofilms.

PMID- 21739683
TI  - [Post-stroke speech disorder treated with acupuncture and psychological
      intervention combined with rehabilitation training: a randomized controlled
      trial].
AB  - OBJECTIVE: To assess the clinical efficacy on post-stroke speech disorder treated
      with acupuncture and psychological intervention combined with rehabilitation
      training. METHODS: The multi-central randomized controlled study was adopted. One
      hundred and twenty cases of brain stroke were divided into a speech
      rehabilitation group (control group), a speech rehabilitation plus acupuncture
      group (observation group 1) and a speech rehabilitation plus acupuncture combined
      with psychotherapy group (observation group 2), 40 cases in each one. The
      rehabilitation training was conducted by a professional speech trainer. In
      acupuncture treatment, speech function area in scalp acupuncture, Jinjin (EX-HN
      12) and Yuye (EX-HN 13) in tongue acupuncture and Lianquan (CV 23) were the basic
      points. The supplementary points were selected according to syndrome
      differentiation. Bloodletting method was used in combination with acupuncture.
      Psychotherapy was applied by the physician in psychiatric department of the
      hospital. The corresponding programs were used in each group. Examination of
      Aphasia of Chinese of Beijing Hospital was adopted to observe the oral speech
      expression, listening comprehension and reading and writing ability. RESULTS:
      After 21-day treatment, the total effective rate was 92.5% (37/40) in observation
      group 1, 97.5% (39/40) in observation group 2 and 87.5% (35/40) in control group.
      The efficacies were similar in comparison among 3 groups. The remarkable
      effective rate was 15.0% (6/40) in observation group 1, 50.0% (20/40) in
      observation group 2 and 2.5% (1/40) in control group. The result in observation
      group 2 was superior to the other two groups (P<0.01, P<0.001). In comparison of
      the improvements of oral expression, listening comprehension, reading and writing
      ability, all of the 3 groups had achieved the improvements to different extents
      after treatment (P<0.01, P<0.001). The results in observation group 2 were better
      than those in observation group 1 and control group. CONCLUSION: Acupuncture and
      psychological intervention combined with rehabilitation training is obviously
      advantageous in the treatment of post-stroke speech disorder.

PMID- 21739684
TI  - [Acupuncture for acute ankle sprain].

PMID- 21739685
TI  - [Rehabilitation evaluation on post-stroke abnormal movement pattern prevented and
      treated with acupuncture and rehabilitation].
AB  - OBJECTIVE: To explore the impacts of acupuncture and rehabilitation on post
      stroke abnormal patterns of limb movement and evaluate them via rehabilitation
      method. METHODS: Ninety cases of post-stroke movement disorder were randomly
      divided into an acupuncture-rehabilitation group, a body acupuncture group and a
      medication group, 30 cases in each group. In medication group, the conventional
      medication in neurological department was administered. In acupuncture
      rehabilitation group and body acupuncture group, on the basis of the therapy as
      medication group, scalp acupuncture (such as parietal area and anterior parietal
      area, etc.), rehabilitation training and traditional body acupuncture [such as
      Jianyu (LI 15) and Fengshi (GB 31),etc.] were supplemented. The continuous
      electric stimulation was applied in body acupuncture group. The treatment lasted
      for 8 weeks. The assessment of clinical efficacy, Fugl-Meyer score, Modified
      Ashworth scale (MAS), range of motion (ROM) and shoulder pain score were taken as
      observation indices for rehabilitation evaluation before and after treatment in
      each group. RESULTS: The effective rate was 93.1% (27/29) in acupuncture
      rehabilitation group, which was superior to 66.7% (20/30) in body acupuncture
      group and 57.1% (16/28) in control group (both P<0.01) separately. After
      treatment, Fugl-Meyer score, MAS, ROM of the lower limbs and shoulder joint and
      shoulder pain score (except medication group) were all remarkably improved as
      compared with those before treatment in each group (all P<0.01). The improvements
      in Fugl-Meyer score, MAS, ROM of the upper limbs and shoulder pain score in
      acupuncture-rehabilitation group were significantly superior to those in body
      acupuncture group and medication group (P<0.05, P<0.01). CONCLUSION: Acupuncture
      and rehabilitation therapy and traditional body acupuncture remarkably improve in
      post-stroke movement disorder. But acupuncture and rehabilitation therapy is
      apparently superior to traditional body acupuncture. This therapy can effectively
      prevent and treat post-stroke abnormal patterns and it is greatly significant in
      the improvement of survival quality for the patients.

PMID- 21739686
TI  - [Efficacy impacts of psychological factors on primary dysmenorrhea treated with
      acupuncture].
AB  - OBJECTIVE: To explore the relationship between psychological factors and efficacy
      of acupuncture on primary dysmenorrhea. METHODS: Sixty cases of primary
      dysmenorrhea were observed. Before acupuncture treatment, the self-designed
      confidence questionnaire was used to assess patients' confidence in acupuncture
      efficacy. Visual Analogue Scale (VAS) was adopted to assess patients' tension
      level during acupuncture. Self-rating anxiety scale (SAS) and self-rating
      depression scale (SDS) were applied to assess the situations of patients' anxiety
      and depression. Eysenck's personality questionnaire (EPQ) and Cattell sixteen
      personality factors questionnaire (16PF) were provided to assess the personal
      characters of patients. Pain intensity, pain duration and accompanied symptoms
      were recorded before and after acupuncture treatment so as to assess the
      efficacy. Canonical correlation analysis was used to analyze the relationship
      between the psychological factors and acupuncture efficacy on primary
      dysmenorrhea. RESULTS: There were significant differences in grading of
      dysmenorrhea, pain intensity score and pain duration after treatment as compared
      statistically with those before treatment (all P<0.001). The standardized
      coefficients of dominance (r=0.6797) and anxiety (r=-0.5906) in personality
      factors and the reduction of pain duration (r=0.9042) among efficacy indices were
      the highest. The overall correlation coefficients were all lower between the
      indices of psychological factors and canonical variables of dysmenorrhea
      efficacy. CONCLUSION: Acupuncture efficacy on primary dysmenorrhea has a certain
      correlation with dominance and anxiety of patients' personality factors. But, the
      psychological factors do not play a leading role in acupuncture treatment.

PMID- 21739687
TI  - [Three kinds of aseptic needle insertion method].

PMID- 21739688
TI  - [Evaluation of the immediate effect of acupuncture on cervical spondylosis of
      vertebral artery type based on orthogonal design].
AB  - OBJECTIVE: To analyze the differences in the immediate effect of acupuncture on
      cervical spondylosis of vertebral artery type among three factors: needling
      technique, acupoint selection and time of needle retaining so as to option the
      best therapeutic program. METHODS: Thirty-two cases were observed and randomly
      divided into 8 groups, 4 cases in each one. The orthogonal design of three
      factors and two levels was adopted. There were needling technique
      (electroacupuncture, reinforcing and reducing method), acupoint selection [C4-C7
      Jiaji (EX-B 2) and three needles of neck: Tianzhu (BL 10), Jingbailao (EX-LHN
      15), Dazhu (BL 11)] and time of needle retaining (5 min, 15 min). L8 (2(7))
      orthogonal design table was arranged in the trial. The changes in mean velocity
      (Vm) of vertebral artery (VA) and basilar artery (BA) were observed before and
      after acupuncture. RESULTS: The immediate effect of VA-BA blood flow was the most
      significant after electroacupuncture at C4-C7 Jiaji (EX-B 2), with continuous
      wave for 5 min. This method and acupoint selection greatly influenced the
      therapeutic results (both P<0.05). CONCLUSION: The optimized therapeutic program
      of the immediate effect of acupuncture for cervical spondylosis of vertebral
      artery type is electroacupuncture + C4-C7 Jiaji (EX-B 2) + 5 min. The importance
      of different factors for the immediate effect in acupuncture treatment of
      cervical spondylosis of vertebral artery type is: acupoint selection > needling
      technique > time of needle retaining.

PMID- 21739689
TI  - [Penetrating needling on head points for vertigo caused by vertebral-basilar
      arterial blood-supply insufficiency].
AB  - OBJECTIVE: To observe the differences in therapeutic effect between penetrating
      needling on head points and acupuncture of syndrome division in the treatment of
      vertigo caused by vertebral-basilar arterial blood-supply insufficiency. METHODS:
      Sixty cases of vertigo caused by vertebral-basilar arterial blood-supply
      insufficiency were divided into 2 groups: a penetrating needling on head points
      group (group A) and an acupuncture of syndrome division group (group B), 30 cases
      in each one. In group A, penetrating needling technique was applied from Baihui
      (GV 20) towards Qianding (GV 21), Shuaigu (GB 8) towards Qubin (GB 7) and Yuzhen
      (BL 9) towards Tianzhu (BL 10). Electric stimulation was added. In group B, the
      acupoints were selected according to syndromes. For example, upper disturbance of
      wind yang: Ganshu (BL 18), Xingjian (LR 2),etc. were selected; upper disturbance
      of turbid phlegm: Yinlingquan (SP 9), Fenglong (ST 40), etc. were selected; qi
      and blood deficiency: Baihui (GV 20), Xuehai (SP 10), etc. were selected; liver
      and kidney yin deficiency: Ganshu (BL 18), Shenshu (BL 23), etc. were selected.
      Electric stimulation and needling manipulation were conducted on those acupoints.
      Ten treatments made one session. After continuous 2 sessions of treatment, the
      efficacy, symptom score and physical sign score were compared between two groups.
      Transcranial Doppler (TCD) examination was done to observe hemodynamic changes of
      anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior
      cerebral artery (PCA) before and after treatment. RESULTS: The total effective
      rate in group A was 96.7% (29/30) that was obviously better than 83.3% (25/30) in
      group B (P<0.05). The scores of vertigo degree, vertigo frequency, duration and
      accompanied symptoms after treatment were lower obviously as compared with those
      before treatment in two groups (all P<0.05). The improvements in group A were
      much significant (all P<0.05). The highest mean velocity(Vm) of bilateral MCA,
      ACA and PCA were apparently reduced after treatment in two groups (P< 0.05,
      P<0.01). The improvements in group A were much more apparently (all P<0.05).
      CONCLUSION: The penetrating needling on head points can effectively relieve
      vertigo caused by vertebral-basilar arterial blood-supply insufficiency, reduce
      the attack frequency and improve in its accompanied symptoms. Its clinical
      efficacy is significantly superior to that in acupuncture of syndrome division
      group.

PMID- 21739690
TI  - [Case of osteonecrosis].

PMID- 21739691
TI  - [Forty-five cases of irritable bowel syndrome (diarrhea type) treated by mouth
      acupuncture].

PMID- 21739692
TI  - [Observation on therapeutic effect of acupoint catgut-embedding combined western
      medicine for epilepsy of generalized seizures type].
AB  - OBJECTIVE: To compare the efficacy differences between acupoint catgut-embedding
      combined western medicine (ACCWM) and simple western medicine (WM) for treatment
      of epilepsy of generalized seizures type. METHODS: Fifty-two patients with
      epilepsy of generalized seizures type were randomly divided into an ACCWM group
      (n=30) and a WM group (n=22). Dazhui (GV 14), Yaoshu (GV 2), Jiuwei (CV 15),
      Qihai (CV 6) were selected in the ACCWM group as the main acupoints combined with
      routine antiepileptic drugs, Valpromide was taken orally, 2.0 g/d for adult, 50
      mg/kg x d for child. The WM group was treated with routine antiepileptic drugs.
      The epilepsy score and the attack frequency one year before the treatment and one
      year during treatment were observed and the therapeutic effects in the two groups
      were compared. RESULTS: The epilepsy score and the attack frequency were both
      decreased in the two groups (P<0.01, P<0.05), and the epilepsy score in the ACCWM
      group decreased significantly (6.57 +/- 3.29 vs 10.73 +/- 2.54, P<0.05). The
      total effective rate of 90.0% (27/30) in the ACCWM group was superior to that of
      68.2% (15/22) in the WM group (P<0.05). CONCLUSION: The therapeutic effect of
      ACCWM is superior to that of simple western medicine in treating epilepsy of
      generalized seizures type. It can improve significantly the attack symptoms so as
      to enhance life quality of the patients with epilepsy.

PMID- 21739693
TI  - [Effects of warming needle moxibustion on improvement of gastrointestinal and
      immune function in patients with postoperation of colorectal cancer].
AB  - OBJECTIVE: To verify the clinical therapeutic effect of warming needle
      moxibustion on improvement of the gastrointestinal and immune function in
      patients with postoperation of colorectal cancer. METHODS: One hundred and five
      patients with postoperation of colorectal cancer were randomly divided into an
      acupuncture and moxibustion group, a Chinese medicine group and a routine
      treatment group, 35 cases in each group. They were all treated with
      gastrointestinal decompression and fluid replacement after operation. The
      acupuncture and moxibustion group was also treated with warming needle
      moxibustion on the 1st day after operation, and Zusanli (ST 36), Shangjuxu (ST
      37) and Xiajuxu (ST 39) etc. were selected, once a day for 10 days, and the
      Chinese medicine group with Simo Decoction oral solution, three times daily for
      10 days. The gastrointestinal function, peripheral blood components and changes
      of T lymphocyte and NK cells in postoperative patients were observed. RESULTS:
      The time of the first bowel sound, exhaust and defecation in the acupuncture and
      moxibustion group were all shorter than those in the Chinese medicine group and
      the routine treatment group (P<0.05, P<0.01). On the 10th day after operation,
      the percentages distribution of lymphocyte and neutrophil in the acupuncture and
      moxibustion group were better than those in the Chinese medicine group and the
      routine treatment group (all P<0.05). The acupuncture and moxibustion group was
      also superior to the Chinese medicine group and the routine treatment group in
      improving the subgroup of T lymphocyte, NK cells and the digestive system
      symptoms (all P<0.05). CONCLUSION: Warming needle moxibustion has a good
      therapeutic effect on gastrointestinal function and can regulate bidirectionally
      peripheral blood lymphocyte and neutrophile granulocyte and improve the T
      lymphocyte subgroup and NK cells so as to promote the recovery of immune function
      in patients with colorectal cancer after operation.

PMID- 21739694
TI  - [Impact of acupuncture on 24 h intraocular pressure of glaucoma].
AB  - OBJECTIVE: To explore the mechanism of acupuncture on the treatment of glaucoma
      so as to find out a kind of simple and effect approach to control and stabilize
      intraocular pressure (IOP) of patients with glaucoma. METHODS: Thirty-nine cases
      (75 eyes) of glaucoma (unstable control of IOP) were treated with acupuncture at
      Sibai (ST 2), Cuanzhu (BL 2), Jingming (BL 1), Qiuhou (EX-HN 7), etc. IOP before
      and after acupuncture, at 10 a.m, 2 p.m, 6 p.m, 10 p.m., at 5 a.m. and 7 a.m. on
      the second day as well as diurnal IOP variation in 24 h were observed separately.
      RESULTS: After acupuncture, IOP at each time point reduced as compared with that
      before acupuncture. IOP at 5 a.m., 7 a.m., 10 a.m., 6 p.m. and 10 p.m. after
      acupuncture was different significantly in statistics as compared with that
      before acupuncture correspondingly (all P<0.05). After acupuncture, 24 h diurnal
      IOP variation was (5.31 +/- 2.84) mmHg, which was lower significantly than (7.06
      +/- 3.86) mmHg before acupuncture (P<0.05). CONCLUSION: For the patients with
      unstable control of IOP, acupuncture can not only reduce IOP, but also stabilize
      24 h diurnal IOP variation and benefit the visual function of patients with
      glaucoma.

PMID- 21739695
TI  - [Comparative study on fMRI of the brain based on Dicang (ST 4), Hegu (LI 4) and
      Houxi (SI 3) on human body].
AB  - OBJECTIVE: To observe the correlation relationship between acupuncture at Dicang
      (ST 4), Hegu (LI 4) and Houxi (SI 3) on the affected side of peripheral facial
      paralysis patients and activated areas in brain functional areas and central
      regulation mechanism of acupuncture at Hegu (LI 4) treatment. METHODS: Eighteen
      cases with left peripheral facial paralysis were randomly divided into a Hegu
      group, a Dicang group and a Houxi group, 6 cases in each group. They were treated
      with electroacupuncture at left Dicang (ST 4), Hegu (LI 4) and Houxi (SI 3),
      respectively, and were examined with fMRI covering the whole brain at the same
      time. The fMRI data was analyzed by SPM software. RESULTS: It was found that the
      left precentral gyrus area and the left postcentral gyrus area were activated
      when electroacupuncture at left Hegu (LI 4), and the right precentral gyrus area
      and the bilateral postcentral gyrus area were activated when electroacupuncture
      at left Dicang (ST 4), and there was no activated area at precentral gyrus area
      and post central gyrus area when electroacupuncture at left Houxi (SI 3).
      CONCLUSION: The sensory importation information from Hegu (LI 4) and Dicang (ST
      4) can converge and coincide in the brain and may influence each other.

PMID- 21739696
TI  - [Interior-exterior relation of meridians under two meridian modes].
AB  - The connotation and core meaning of interior-exterior relation of meridians were
      studied and analyzed on the base of two meridian modes, namely the original
      meridian model and the zang-fu-meridian model. And it was concluded that
      different features and meanings can be found under the above two models. 1)
      Original meridian model: six-coincidence theory in Lingshu: Jingbie (Miraculous
      Pivot: Divergent Meridian) is the core of interior-exterior relation of
      meridians; collaterals (connecting point) play a very important role in
      communicating the interior-exterior relation of meridians. 2) Zang-fu-meridian
      model: zang-fu organ coincidence can promote the matching and communication of
      meridians with interior-exterior close relationship; circulation of qi and blood
      has a positive impact on interiorly and exteriorly related meridians.

PMID- 21739697
TI  - [Study on the relative specificity of the heart and lung meridians in brain with
      fMRI].
AB  - OBJECTIVE: To study the central modulation mechanism on the relative specificity
      of the Heart and Lung Meridians and to provide the experimental evidence for
      deeply study on correlation between meridian-viscera and brain. METHODS: Ten
      healthy students in Anhui College of TCM were chosen and a modified block design
      was adopted. After 32 time points of resting and 32 of rotation needling, then 48
      of resting and 32 stimulating, and 16 resting time points, functional imagings
      were collected at last. All the process would last for 10 min 44 sec. Acupuncture
      work was finished by one acupuncturist with extensive experience by acupuncture
      at the left Shenmen (HT 7) or Taiyuan (LU 8) with the disposable sterile
      stainless steel needle, and uniform reinforcing-reducing method was used with
      frequency of 1 Hz and depth of 1.0 cm. After the experiment, the sensation of
      acupuncture and the other feeling or psychic process were inquired and recorded
      detailedly. These data were analyzed by AFNI software. RESULTS: Acupuncture at
      Taiyuan (LU 8) could excite the contralateral frontal lobe, apical lobe, cerebral
      ganglion, VI, VIII areas and inferior semilunar lobule of cerebellum, and
      restrain bilateral callosal gyrus and homolateral gyrus rectus. Acupuncture at
      Shenmen (HT 7) could excite the contralateral IV-VIII areas of cerebellum, and
      homolateral VI, VII areas of cerebellum, and restrain parts of homolateral apical
      lobe. CONCLUSION: Acupuncture at Shenmen (HT 7) of the Heart Meridian and Taiyuan
      (LU 8) of the Lung Meridian can excite or restrain different brain areas,
      indicating that there are relatively specific corresponding brain areas for the
      Heart Meridian and Lung Meridian.

PMID- 21739698
TI  - [Effects of electroacupuncture and acupoint catgut-embedding on mRNA expression
      of lipid metabolism gene PPAR-gamma and related lipase of rats with simple
      obesity].
AB  - OBJECTIVE: To study the mechanism of electroacupuncture and acupoints catgut
      embedding in losing weight. METHODS: Simple obesity was induced in male SD rats
      with high-fat and high-glucose diet for 10 weeks. Thirty-six rats with obesity
      were randomly divided into model-control group, electroacupuncture (EA) group and
      catgut-embedding (CE) group, with 12 rats in each group. Another 12 normal SD
      rats serving as controls (normal control group) were fed by standard rat chow.
      Rats in the EA group were treated with electroacupuncture at bilateral acupoints
      of "Housanli" (ST 36), "Tianshu" (ST 25), and "Pishu" (BL 20), once daily for
      consecutive 15 days. Rats in the CE group were treated with catgut-embedding at
      the same acupoints with the EA group, once every 7 days. Rats in the other two
      groups were not interfered. After 15 days of treatment, changes of body weight
      were observed, the levels of total cholesterol (TC), triglyceride (TG) and low
      density lipoprotein cholesterol (LDL-C) in serum were assayed, the activities of
      lipoprotein lipase (LPL) and hepatic lipase (HL) in liver tissues were measured,
      and the mRNA expression levels of Peroxisome proliferators activated receptor
      gamma (PPAR-gamma) in adipose tissues were determined. RESULTS: After the
      intervention, body weight and increase of body weight in the EA and CE groups
      were significantly lower than those in the model-control group (all P<0.01).
      Compared with the normal control group, there was significant increasing of
      levels of TC and LDL-C in serum (both P<0.01), descending activities of LPL and
      HL in liver tissues (P<0.05, P<0.01), and decreased expression levels of PPAR
      gamma mRNA in adipose tissues in the model-control group (P<0.05). Compared with
      the model-control group, there were obviously decreased in TC, LDL-C Level in
      serum in EA and CE groups (P<0.05, P<0.01), while there was no difference in TG
      levels among three groups (P>0.05). The activities of LPL and HL were also
      significantly enhanced in EA and CE groups as compared with those in the model
      control group (P<0.01, P<0.05), so were the expression levels of PPAR-gamma mRNA
      in adipose tissues (both P<0.01). CONCLUSION: Electroacupuncture and acupoint
      catgut-embedding can regulate the lipid metabolic disorders in rats with obesity
      through enhancing the expression of PPAR-gamma mRNA in adipose tissues,
      activating the activities of LPL and HL and decreasing the levels of TC and LDL-C
      in serum.

PMID- 21739699
TI  - [Clinical observation on acupotomy for treatment of simple obesity].
AB  - OBJECTIVE: To compare the efficacy differences among acupotomy,
      electroacupuncture and acupuncture for treatment of simple obesity. METHODS: One
      hundred and five cases were randomly divided into an acupotomy group, an
      electroacupuncture group and an acupuncture group, 35 cases in each group, and
      Zhongwan (CV 12), Tianshu (ST 25), Shangjuxu (ST 37), Sanyinjiao (SP 6), etc,
      were selected in three groups and also with selection of acupoints according to
      symptoms. The acupotomy group was treated with acupotomy 40 mm in length and 0.6
      mm in diameter, the electroacupuncture group with the Han's LH402A
      electroacupuncture stimulator and the acupuncture group with simple acupuncture
      treatment. The clinical therapeutic effects of three groups were compared. The
      obesity signs such as body weight, body mass index (BMI), obesity degree, etc.,
      and blood lipid and fasting blood sugar (FBS) were observed. RESULTS: The
      markedly effective rate of 91.4% (32/35) in the acupotomy group was higher than
      that of 71.5% (25/35) in the electroacupuncture group and that of 42.9% (15/35)
      in the hand acupuncture group (both P<0.05). There were significant differences
      in the obesity signs and blood fat and FBS of the three groups before and after
      treatment (P<0.05, P<0.01). The differences rates of body weight, BMI, obesity
      degree, chest circumference, waistline, thighline, waist-hip ratio, total
      cholesterol before and after treatment in the acupotomy group were all better
      than those in the electroacupuncture group and in the acupuncture group (all
      P<0.05), and the differences rates of hipline, FBS in the acupotomy group were
      better than those in the acupuncture group (both P<0.001). CONCLUSION: Acupotomy
      treatment can obviously reduce fat, FBS and blood lipid and has obvious
      therapeutic effects on simple obesity.

PMID- 21739700
TI  - [Randomized controlled study on electroacupuncture compound anesthesia in
      radiofrequency ablation for hypertrophic inferior turbinate].
AB  - OBJECTIVE: To explore the feasibility of electroacupuncture compound anesthesia
      in radiofrequency ablation for hypertrophic inferior turbinate. METHODS: The
      patients confirmed to the enrolled criteria were randomly divided into an
      observation group (n = 31) and a control group (n = 30). The observation group
      was treated with electroacupuncture at Sibai (ST 2), Xiaguan (ST 7), Hegu (LI 4)
      and Zhigou (TE 6) on the left side and routine local anesthesia on the right
      side. The control group was treated with routine local anesthesia on the both
      side. The feelings of pain, circulatory index and operation effect were observed
      and compared. RESULTS: During radiofrequency ablation, the pain grade of two
      measurements on the left side and the 2nd measurement on the right in the
      observation group were all lower than those in the control group (all P<0.05). In
      the observation group, the pain grades on the left side were lower than that on
      the right side (P<0.05), and the systolic blood pressure and the heart rate were
      lower than that in the control group when undergoing the 2nd radiofrequency
      ablation on the right side and on the left side, respectively (both P<0.05).
      There was no significant difference in operation effect between the two groups.
      CONCLUSION: Electroacupuncture compound anesthesia can meet the analgesia
      requirement of radiofrequency ablation for treatment of hypertrophic inferior
      turbinate, and would be helpful to prevent cyclic fluctuation during the
      operation at the same time.

PMID- 21739701
TI  - [One hundred and eighty-six cases of chloasma treated by acupuncture at facial
      division combined with point injection].

PMID- 21739702
TI  - [Cases of pruritus vulvae and swelling].

PMID- 21739703
TI  - [Basic system of Chinese acupuncture standards].

PMID- 21739704
TI  - [Thirty cases of knee osteoarthritis treated by acupuncture and warming needle
      moxibustion].

PMID- 21739705
TI  - [Case of glossopharyngeal nerve paralysis].

PMID- 21739706
TI  - [Acupuncture messenger--Pu Xiang-cheng].
AB  - PU Xiang-cheng is the eminent acupuncture master in modern history of China. He
      studied diligently in early years and devoted his life to the cause of
      acupuncture practice and education in Chinese medicine. Combination of
      acupuncture and herbal medicine, coordination of acupuncture and moxibustion,
      unique application of acupoints, flexible combination of acupoints and focusing
      on needling techniques are the essence of his academic thoughts. The life of PU
      Xiang-cheng, the acupuncture master, and his major academic thoughts are
      described in this paper, so as to commemorate his contributions to acupuncture
      theory, practice and promotions.

PMID- 21739707
TI  - [Twenty-two cases of spastic type heatstroke treated by acupuncture and
      moxibustion].

PMID- 21739708
TI  - [Forty-two cases of malaria treated with ginger-partitioned moxibustion in the
      Republic of Congo].
AB  - OBJECTIVE: To observe the clinical efficacy of ginger-partitioned moxibustion on
      malaria in Congo. METHODS: Ginger-partitioned moxibustion was applied mainly to
      Dazhui (GV 14) and Mingmen (GV 4). For malaria of common type, Taodao (GV 13) was
      added in moxibustion. For gastrointestinal type, Pishu (BL 20) was added in
      moxibustion. For pain type, cupping on local Ashi points was combined. For common
      cold type, moving cupping on Bladder Meridian was combined. Moxibustion was
      applied once every 3 days and 5 treatments made one session. RESULTS: Thirty-one
      cases were cured, 8 cases improved and 3 cases failed. The effective rate was 92.
      9%. CONCLUSION: Ginger-partitioned moxibustion has significant efficacy on
      malaria in Congo.

PMID- 21739709
TI  - [Case of Dope-reactive dystonia].

PMID- 21739710
TI  - [Case of spasmodic torticollis].

PMID- 21739711
TI  - [Acupuncture and Tuina in Namibia].
AB  - The development of acupuncture-moxibustion and Tuina in Namibia was introduced in
      the article. The history of acupuncture in Namibia is only 15 years, and there
      are 3 acupuncturists and Tuina practitioners with permanent resident permit in
      Namibia. The University of Namibia has already established a medical college,
      which is now cooperating with the concerning Chinese medical university of China
      and carrying out education for the undergraduate students. The development of
      acupuncture-moxibustion and Tuina has a great potential in Namibia with an
      extensive indication involving diseases of internal medicine, surgery,
      gynecology, pediatrics, orthopedics, and neurology.

PMID- 21739712
TI  - [Case of bilateral diaphragm paralysis].

PMID- 21739713
TI  - [Acupuncture at Shousanli (LI 10) combined with cupping therapy for strained
      neck].

PMID- 21739714
TI  - [Existing state of meridians and experimental difficulties].
AB  - The existing state of meridians through study of thinking way of unity of
      subjective and objective of the ancient people was discussed in this paper, so as
      to review the experiments on meridians. The result indicates that the
      construction of meridian theory is a life experience of checking the interior of
      the body, and it is considered that meridians and collaterals are the projects of
      the mind to the trunk and limbs under the condition of physical and psychological
      unification. It often differs from the experimental medicine in the
      identification of ultimate facts. Therefore, meridians revealed by experiments
      probably greatly differ from its actual existing state. Thus, experimental study
      of meridian should focus on theory of traditional Chinese medicine concerning the
      body, energy and the mind, and be applied to verify the experimental result.

PMID- 21739715
TI  - [Forty cases of chronic prostatitis/chronic pelvic pain syndrome treated by
      acupuncture and crude herb moxibustion].

PMID- 21739716
TI  - [Advances of studies on relieving of exercise-induced fatigue by transcutanclus
      electrical acupoint stimulation].
AB  - The occurrence of exercise-induced fatigue can be delayed and exercise endurance
      can be strengthened by removing lactic acid, decreasing serum creatine kinase,
      elevating hemoglobin, maintaining blood glucose, eliminating free radical,
      regulating amino acid metabolism and retaining heart rate with transcutanclus
      electrical acupoint stimulation (TEAS). Problems in the above researching field
      are generalized in this paper. For instance, the point selection is relatively
      simple; the selection of wave band, frequency and duration during the application
      of TEAS apparatus are not unified; and observation indices mainly remained in the
      aspect of biochemistry. It also prospects the future directions of TEAS relieving
      exercise-induced fatigue including selecting acupuncture point by differentiation
      of symptoms and signs, setting uniform standards for TEAS, and studying the
      mechanisms of TEAS relieving exercise-induced fatigue by testing gonadal axis,
      adrenal axis, gene and protein.

PMID- 21739717
TI  - [Management of intraoperative pulmonary artery injuries].

PMID- 21739718
TI  - [History of aortic surgery].

PMID- 21739719
TI  - [Imaging diagnosis Q & A: mitral valve insufficiency].

PMID- 21739720
TI  - Significant differences in global genomic DNA methylation by gender and
      race/ethnicity in peripheral blood.
AB  - Reduced levels of global DNA methylation are associated with genomic instability
      and are independent predictors of cancer risk. Little is known about the
      environmental determinants of global DNA methylation in peripheral blood. We
      examined the association between demographic and lifestyle factors and levels of
      global leukocyte DNA methylation in 161 cancer-free subjects enrolled in the
      North Texas Healthy Heart Study aged 45-75 years in 2008. We used in-person
      interviews for demographics and lifestyle factors, a self-administrated Block
      food frequency questionnaire for diet, and bioelectrical impedance analysis and
      CT-scan for body composition. We measured genomic DNA methylation using bisulfite
      conversion of DNA and pyrosequencing for LINE-1. Body composition measures
      including body mass index, waist circumference, areas of subcutaneous fat and
      visceral fat, percent of fat mass and fat-free mass were not associated with
      global genomic DNA methylation after controlling the effect of age, gender and
      race/ethnicity. Instead, female gender was significantly associated with a
      reduced level of global methylation (beta = -2.77, 95% CI: -4.33, -1.22).
      Compared to non-Hispanic whites, non-Hispanic blacks (beta = -2.02, 95% CI: 
      3.55, -0.50) had significantly lower levels of global methylation. No association
      was found with age, cigarette smoking, alcohol drinking and dietary intake of
      nutrients in one-carbon metabolism. Global leukocyte DNA methylation differs by
      gender and race/ethnicity, suggesting these variables need to be taken into
      consideration in studies of global DNA methylation as an epigenetic marker for
      cancer.

PMID- 21739721
TI  - An acetylation-mono-ubiquitination switch on lysine 120 of H2B.
AB  - Post-translational modifications (PTMs) of histones are crucial for
      transcriptional control, defining positive and negative chromatin territories. A
      switch of opposing functional significance between acetylation and methylation
      occurs on many residues. Lysine 120 of H2B is modified by two PTMs:
      ubiquitination, which is required for further trans-tail H3 methylations and
      elongation, and acetylation, whose role is less clear. ChIP-Seq with MNase I
      treated chromatin indicates that H2BK120ac is present on nucleosomes immediately
      surrounding the TSS of transcribed or poised units, but not in core promoters. In
      kinetic ChIP analysis of ER-stress inducible genes, H2BK120ac precedes activation
      and H2B-ub deposition. Using in vitro acetylation assays, pharmacologic
      inhibition and RNAi, we established that KAT3 is responsible for H2BK120ac.
      Interestingly, the global levels of H2B-ub decreased in KAT3-inactivated cells.
      However, RNF20 recruitment was not impaired by KAT3-inactivation. Our data point
      at acetylation of Lysine 120 of H2B as an early mark of poised or active state
      and establish a temporal sequence between acetylation and mono-ubiquitination of
      this H2B residue.

PMID- 21739722
TI  - NCCN collaborates to alleviate adult cancer pain in China.

PMID- 21739723
TI  - National Business Group on Health launches major initiative to address cancer in
      the workplace.

PMID- 21739724
TI  - New therapies for metastatic disease addressed in updated NCCN Guidelines for
      breast cancer.

PMID- 21739725
TI  - Post-transplant lymphoproliferative disorder section integrated into updated NCCN
      Guidelines for NHL.

PMID- 21739726
TI  - NCCN panel calls for higher standards, better ways of translating molecular
      genetics into clinical practice.

PMID- 21739727
TI  - Active surveillance monitoring more stringent in updated NCCN Guidelines for
      prostate cancer.

PMID- 21739728
TI  - Foreword: Follow-on Biologics: Implementation Challenges and Opportunities.
AB  - This Book of the Seton Hall Law Review presents the contributions to Follow-On
      Biologics: Implementation Challenges and Opportunities, a one-day roundtable
      event hosted by Seton Hall University School of Law in the fall of 2010. The
      roundtable fostered an international dialogue regarding the future of follow-on
      biologics in the United States resulting from the Patient Protection and
      Affordable Care Act of March 2010. THE BIOLOGIC PRICE COMPETITION AND INNOVATION
      ACT OF 2010. The March 23, 2010, enactment of the Patient Protection and
      Affordable Care Act (PPACA) and the companion Health Care and Education
      Affordability Reconciliation Act of 2010 ushered in landmark reform of the
      American health care system. Along with sweeping overhauls of the health care
      system generally, PPACA also provides a new regulatory challenge for the Food and
      Drug Administration (FDA). A subtitle within PPACA, the Biologics Price
      Competition and Innovation Act (BPCIA), bestows upon FDA broad authority to
      implement an abbreviated approval route to market for biological products (also
      known as biologics) that are "biosimilar" to an existing marketed product. The
      brief introduction will provide a basic comparison of biologics and conventional
      pharmaceutical drugs that will prove central to the FDA's development of this
      follow-on biologic pathway as well as specifically examine the content and scope
      of the BPCIA provisions and identify future challenges for the FDA. It will
      conclude by highlighting details of presentations during the roundtable held at
      the Seton Hall University School of Law and introduce the two resulting articles
      contained with this Book of the Seton Hall Law Review.

PMID- 21739729
TI  - Empowering women to develop their own health service.

PMID- 21739730
TI  - Meeting the challenge: implementing the Baby Friendly Hospital Initiative in a
      culturally diverse country.
AB  - This paper describes the successful implementation of the WHO/Unicef Baby
      Friendly Hospital initiative (BFHI) in a large, culturally diverse hospital in
      the United Arab Emirates (UAE). Breastfeeding rates in the UAE are high (>90 per
      cent), although mixed feeding is considered the norm. Traditional religious
      practices for birth are common which may inhibit exclusive breastfeeding. An
      action research methodology was chosen as the most appropriate method in which to
      implement BFHI and a five stage cyclic approach was used. Staff knowledge around
      breastfeeding and BFHI varied enormously because of the diversity of ethnicity
      amongst staff. It was initially difficult to engage staff, particularly staff in
      the delivery suite and theatres, as breastfeeding was not seen as a high
      priority. There was a great resistance to closing the nurseries as both women and
      staff felt it was a benefit for the women to have some rest away from their
      babies, and the concepts of bonding and early feeding cues were unknown. By the
      time of the assessment for BFHI there was a theory-practice transformation. The
      implementation of BFHI and the successful achievement of the award can be
      attributed to ownership.

PMID- 21739731
TI  - European Midwives Project: supervision in action.
AB  - Midwives from the European Union are registering with the NMC, enabling them to
      work in the UK, as their Midwifery training programmes meet the minimum standards
      required. It has become apparent that although midwives were previously eligible
      to practise in the UK, they often found it hard to secure employment or they were
      employed in a supernumery capacity for a period of time until employers and
      supervisors considered that the midwife was actually fit to practise clinically.
      In some instances the period of effective registration expired or was about to
      expire as employment could not be gained and practice hours maintained as
      required by Post Registration Education and Practice (PREP) (NMC 2008a). The West
      Midlands Supervisory Authority and Birmingham City University have responded to
      this problem by providing the European Midwifery Programme.

PMID- 21739732
TI  - C'est la midwifery!
AB  - The French health care system has long been considered one of the best in the
      world. When it comes to childbirth, French mothers accept the medicalised
      approach. In Britain, mothers want choice over how and where to give birth. Anne
      Gambler, independent French midwife living in London, and Denise Linay,
      spokesperson for the Royal College of Midwives, talk about midwifery and
      childbirth.

PMID- 21739733
TI  - Positively essential: traditional birth attendants in Malawi.
AB  - One of the biggest challenges for healthcare professionals working in developing
      countries is the lack of trained personnel to carry out much needed health care
      provision. Shirley Stronge worked as a nurse/midwife tutor in a rural area in the
      north of Malawi. Millennium Development Goals four and five have focused our
      attention on the care required by mothers and newborns. Shirley has chosen to
      reflect on the role of Traditional Birth Attendants in the north of Malawi and
      their positive impact on maternity services in this area.

PMID- 21739734
TI  - Turning the clock back.
AB  - This is a reflection of one of the best times of Jane Wanless's life, having the
      opportunity to live and work in another country, in another culture with the
      people she loved most with her. There are many other reasons why New Zealand will
      always hold a special place in Jane's heart, but as a midwife, she found the care
      to be truly women centred, where normality and continuity led on to long lasting
      trusting relationships between the midwives and the families they cared for.

PMID- 21739735
TI  - Implementing midwifery led care in Pakistan.
AB  - Pakistan's maternal and neonatal mortality rate compares unfavourably with the UK
      and much of the world (McIntyre 2010). The high rates of maternal and neonatal
      mortality in Pakistan are due to inadequate maternal, neonatal and child care,
      too few skilled birth attendants, insufficient competent midwives, ineffective
      and unaffordable basic and comprehensive emergency obstetric services. In this
      article, the introduction of the first midwifery led units in an urban hospital
      setting in Karachi, its rationale and projected future plans will be described.

PMID- 21739736
TI  - On a mission: training traditional birth attendants in Ethiopia.
AB  - Alice Ciolino, a midwife from London spent eight months in Ethiopia with Doctors
      of the World. Her mission was to train Traditional Birth Attendants (TBAs). Based
      in the Somali region of Ethiopia, access to healthcare facilities was limited;
      indeed Kebri Dehar had the only hospital in the region. Here Alice shares her
      experience of what it is like to live and work in a remote part of the world, far
      from the medical facilities we take for granted in the West.

PMID- 21739737
TI  - Can the importance of midwives be measured in deaths?
AB  - The devastating consequences of maternal mortality are nowhere more evident than
      in Uganda, where more than 6000 mothers die as a result of childbearing every
      year (WHO 2010). Maternal death not only devastates the families concerned but
      harms future generations in terms of economic and social stability. Most of the
      maternal deaths in sub-Saharan Africa could be prevented by the attendance of a
      midwife. In Gulu, Northern Uganda, 60 per cent of women birth unattended. The
      facts surely speak for themselves. The world needs midwives now more than ever.
      Midwives have the potential to affect health on an individual and global scale
      and we should not underestimate the potential of the profession.

PMID- 21739738
TI  - Skin-to-skin contact. Part two: the evidence.
AB  - Health professionals are increasingly recognising that skin-to-skin contact
      between mother and baby immediately after birth has important and significant
      health benefits for all babies. UNICEF UK Baby Friendly Initiative has recently
      increased recommended minimum time spent in skin contact after birth from 30
      minutes to one hour. This article looks at recent research into the benefits of
      skin contact and summarises the findings.

PMID- 21739739
TI  - Relatively speaking...

PMID- 21739740
TI  - Swimming with the dolphins.

PMID- 21739741
TI  - Encopresis: a medical and family approach.
AB  - Bowel control is an important developmental milestone for children. Failure to
      achieve or loss of bowel control by five years of age threatens both physical and
      mental health. Most children are successful at achieving bowel control by age
      four, but up to 3% of the pediatric population suffer from encopresis. Three in
      depth case studies were reviewed, including the causes, symptoms, and treatment
      of this condition, one of which is presented in this article. Results indicate
      that treatment was successful when a combined approach using medical and
      behavioral strategies within the context of a developmental model was used. These
      results can be used by pediatric nurses, nurse practitioners, and pediatricians
      to assure more children will be identified and obtain the support they need for
      successful treatment of this complex condition.

PMID- 21739742
TI  - Case study: aphthous ulcers in a 14-year-old girl.
AB  - Recurrent aphthous ulcers (RAUs), also known as canker sores, aphthous
      stomatitis, or aphthae, are a very common and often painful condition presenting
      in primary care. The majority of aphthous ulcers are benign, time-limited (7 to
      14 days), and in some cases, require pain management until healed. However, RAUs
      can be a manifestation of a serious health condition, such as an autoimmune
      disorder, human immunodeficiency virus, infection, and hematologic or oncologic
      conditions. Initially, the most important priority in caring for these patients
      is to obtain a complete history and physical examination to rule out systemic
      disease and lead to an accurate diagnosis and plan of care.

PMID- 21739743
TI  - Pediatric nurses' attitudes toward hospice and pediatric palliative care.
AB  - Several studies have investigated nurses' attitudes toward hospice and palliative
      care for adults, yet little information exists about pediatrics. Assessing
      pediatric nurses' attitudes is especially important in Florida, where a publicly
      funded pediatric palliative care program operates in eight cities across the
      State. The aims of this study were 1) to assess the attitudes toward hospice and
      palliative care, and 2) to examine the associations between sociodemographic and
      nursing care factors and nurses' attitudes toward hospice and palliative care. A
      cross-sectional research design using online and mail-in survey data was used to
      address the study aims. Surveys were conducted with 279 pediatric nurses across
      Florida. Bivariate results showed there were significant differences between the
      attitudes of pediatric nurses employed in a city with a pediatric palliative care
      program versus those not employed in a program site (p = 0.05). Multivariate
      analyses also showed that being employed in a program site increased attitudinal
      scores toward hospice and pediatric palliative care by 0.6 points. Beyond being
      employed in an area city where a pediatric palliative care program operates,
      results also suggest that having prior training in palliative care could alter
      nurses' attitudes, which might subsequently lead to increased referrals and
      improved outcomes for children and families.

PMID- 21739744
TI  - Demystifying the research process: cross-sectional design.

PMID- 21739745
TI  - Breathing easy: implementing a bronchiolitis protocol.
AB  - In 2005, a protocol for patients with bronchiolitis in the pediatric unit was
      created, but compliance was less than desired. Therefore, revisions based on
      staff feedback and current literature were implemented in 2007. A pre- and post
      implementation design was used. Descriptive statistics were used to measure the
      following variables: use of protocol, frequency of suctioning, use of beta2
      agonist medication, length of stay, and charges per case. A chart review was
      used. After implementing the revised protocol, improvement in all areas was
      demonstrated. Protocol use went from 20% to 68%; suctioning per protocol went
      from 9% to 66%, beta2-agonist medication use dropped from 70% to 48% (desired
      change). Financial measures also showed improvement; a decrease in length of stay
      (2.23 from 3.25 days), and a decrease in charges of $1000/case were demonstrated.

PMID- 21739746
TI  - A 10-year-old with anxiety and history of asthma.

PMID- 21739747
TI  - Incorporating mental health checkups into adolescent primary care visits.

PMID- 21739748
TI  - The ethical rights of children: yesterday and today.

PMID- 21739749
TI  - Child abuse prevention program wins NACHRI award--a journey.

PMID- 21739750
TI  - Going green in the OR brings financial, environmental gains.

PMID- 21739751
TI  - Value-based purchasing rule is final.

PMID- 21739752
TI  - Expert's advice video integration.

PMID- 21739753
TI  - Video integration for 21st century.

PMID- 21739754
TI  - Video: what's here? What's coming?

PMID- 21739755
TI  - Sharing lessons from video projects.

PMID- 21739756
TI  - How are you doing on high-level disinfection?

PMID- 21739757
TI  - Managing SSI surveillance in an ASC.

PMID- 21739758
TI  - Implementation of the biosimilar pathway: economic and policy issues.

PMID- 21739759
TI  - Informed by the European Union experience: what the United States can anticipate
      and learn from the European Union's regulatory approach to biosimilars.

PMID- 21739760
TI  - Looking inward: regional parallel trade as a means of bringing affordable drugs
      to Africa.

PMID- 21739761
TI  - The need for federal preemption of state tort claims in the context of "new
      drugs" and premarket-approved medical devices.

PMID- 21739762
TI  - Reforming New Jersey's vaccination policy: the case for the Conscientious
      Exemption Bill.

PMID- 21739763
TI  - Baseball's DNA testing policy strikes out: genetic discrimination in major league
      baseball.

PMID- 21739764
TI  - [When the past catches up with us...].

PMID- 21739765
TI  - Administrative simplification: adoption of operating rules for eligibility for a
      health plan and health care claim status transactions. Interim final rule with
      comment period.
AB  - Section 1104 of the Administrative Simplification provisions of the Patient
      Protection and Affordable Care Act (hereafter referred to as the Affordable Care
      Act) establishes new requirements for administrative transactions that will
      improve the utility of the existing HIPAA transactions and reduce administrative
      costs. Specifically, in section 1104(b)(2) of the Affordable Care Act, Congress
      required the adoption of operating rules for the health care industry and
      directed the Secretary of Health and Human Services to "adopt a single set of
      operating rules for each transaction * * * with the goal of creating as much
      uniformity in the implementation of the electronic standards as possible." This
      interim final rule with comment period adopts operating rules for two Health
      Insurance Portability and Accountability Act of 1996 (HIPAA) transactions:
      eligibility for a health plan and health care claim status. This rule also
      defines the term "operating rules" and explains the role of operating rules in
      relation to the adopted transaction standards. In general, transaction standards
      adopted under HIPAA enable electronic data interchange through a common
      interchange structure, thus minimizing the industry's reliance on multiple
      formats. Operating rules, in turn, attempt to define the rights and
      responsibilities of all parties, security requirements, transmission formats,
      response times, liabilities, exception processing, error resolution and more, in
      order to facilitate successful interoperability between data systems of different
      entities.

PMID- 21739766
TI  - U.S. nursing schools transform master's education by adopting new standards
      reflecting contemporary nursing practice.

PMID- 21739767
TI  - Gaps in practice.

PMID- 21739768
TI  - IV iron replacement.

PMID- 21739769
TI  - Malignant pleural mesothelioma: clinicopathologic and survival characteristic in
      a consecutive series of 40 patients.
AB  - INTRODUCTION: Pleural malignant mesothelioma is an uncommon but extremely
      invasive tumor which originates from mesothelial cells and usually occurs after
      prolonged exposure to asbestos. Different types of surgical and oncological
      therapeutic methods have been used resulting in various outcomes. The aim of this
      study was to evaluate, clinicopathologically, 40 patients with pleural malignant
      mesothelioma and the main factors influencing their prognosis. METHODS: In this
      study, 40 patients with a definitive diagnosis, who had been followed up for at
      least 3 years were studied according to these: epidemiologic factors, stage and
      pathological types, treatment method and complications, and by using factors that
      influence patients survival, we evaluated them statistically. RESULTS: The M/F
      ratio was l3/1 with an average age of 55 years. Chest pain was the most common
      symptom. In 55% of patients, the lesions were localized in the left site and most
      were in Buchart stage I or II. The epithelial form was the most common
      pathological pattern (62.5%). 47.5% of patients only received radiotherapy and
      chemotherapy. Of patients who underwent decortication and pleurectomy with
      adjuvant therapy, extrapleural was performed in 20% of patients, and
      pneumonectomy, in 17.5%; and 15% refused any type of treatment. One patient died
      from the surgery. The most common surgical complication was wound infection. The
      average survival was 10.5 months, and the main factors influencing the survival
      were physiologic status, pathological form of disease, stage of disease and the
      pattern of pleural involvement. CONCLUSION: Because of the low survival after
      multimodality invasive treatments in mesothelioma, aggressive therapeutic methods
      were recommended in patients with good physiological status and early clinical
      stage with a good pathology type.

PMID- 21739770
TI  - Hyperbaric medicine.

PMID- 21739771
TI  - Nuclear medicine.

PMID- 21739772
TI  - Supplement: scope of practice for massage therapists.

PMID- 21739773
TI  - IV iron replacement.

PMID- 21739774
TI  - Wasted skills.

PMID- 21739775
TI  - Truth telling dilemma.

PMID- 21739776
TI  - Unionised workplaces make the difference.

PMID- 21739777
TI  - Telehealth connecting care.

PMID- 21739779
TI  - Super? It's sorted!

PMID- 21739778
TI  - Nurses in general practice: a moving force.

PMID- 21739780
TI  - How safe is the health care workplace for staff and consumers?

PMID- 21739781
TI  - Reflection: debriefing students returning from community practice.

PMID- 21739782
TI  - Assignments with Medecins Sans Frontieres.

PMID- 21739783
TI  - Pain management.

PMID- 21739784
TI  - Screening for dysphagia.

PMID- 21739785
TI  - Continuing professional development--what's old is new.

PMID- 21739787
TI  - NMC asks employers to resolve minor misconduct allegations.

PMID- 21739786
TI  - A question of dignity.

PMID- 21739788
TI  - Lansley attacks NHS hospitals that 'fail to get the basics right'.

PMID- 21739789
TI  - NHS direct staff win right to decide on weekend shift work.

PMID- 21739790
TI  - Trusts urged to cut their agency spend as pay regulations loom.

PMID- 21739791
TI  - Link between staffing levels and outcomes cannot be ignored.

PMID- 21739792
TI  - The secrets of student success.

PMID- 21739794
TI  - Chorus of approval.
AB  - Joining a choir is proving therapeutic for patients with cancer and their
      relatives.

PMID- 21739793
TI  - The voice of experience.
AB  - The chief executive of one of London's major hospitals, Heather Lawrence, has
      never forgotten her nursing roots.

PMID- 21739795
TI  - Major talking point.
AB  - While mobile phone use is now an accepted part of everyday life, nurses using
      them in the course of their work need to be aware of the potential risks
      involved.

PMID- 21739796
TI  - Reversal of fortunes.
AB  - Nurse Jeanette Singer has pioneered care for children with liver disease and
      their families.

PMID- 21739797
TI  - Managing the care of patients with herpes zoster ophthalmicus.
AB  - The herpes zoster virus is a common neurocutaneous infection. When the eye is
      involved, the virus is referred to as herpes zoster ophthalmicus. This article
      discusses the role of the nurse in managing the care of patients with herpes
      zoster ophthalmicus. It provides an overview of the condition and its associated
      pathophysiology. The article examines risk factors, clinical features, diagnosis,
      treatment, complications and prevention. It also discusses the care required to
      support patients during their treatment and subsequent rehabilitation.

PMID- 21739798
TI  - A critique of positive thinking for patients with cancer.
AB  - This article provides a critical reflection of the debate regarding the adoption
      of positive thinking in the care and recovery of patients with cancer. Positive
      thinking is an approach characterised by adopting a fighting spirit, taking
      control and being strong and brave. The association of positive thinking with a
      range of favourable outcomes has been challenged.

PMID- 21739799
TI  - Travel-related health and safety considerations for children.
AB  - Paediatrics is an integral part of travel medicine. More children are travelling
      overseas to increasingly remote destinations. All practitioners who come into
      contact with infants and children, whether in designated travel clinics or
      general practice settings, need to be aware of travel-related concerns. This
      article addresses the importance of travel-related health and safety for children
      and the provision of appropriate advice to parents and guardians.

PMID- 21739800
TI  - Cancer cachexia.

PMID- 21739801
TI  - Named then shamed.

PMID- 21739802
TI  - Earthquake aftermath.

PMID- 21739803
TI  - Seeing it both ways.

PMID- 21739804
TI  - Exceeding expectations for electronic billing. You may see more cash through the
      door and even improve communications with all parties involved when you implement
      the right automated workflow.

PMID- 21739805
TI  - Robots expand delivery options with seamless integration. A growing number of
      forward-thinking hospitals in search of greater efficiencies are embracing
      automated delivery robots.

PMID- 21739806
TI  - Finding leaks in hospital workflow. The biggest problems can be found where you
      least expect them.

PMID- 21739807
TI  - On a mission to eradicate paper. Implementing a document management system paves
      the way for electronic medical records.

PMID- 21739808
TI  - Protect patient from an inside job. A layered approach, including safeguards
      against your own privileged users, may be your best bet for data security.

PMID- 21739809
TI  - Ensuring safety through wireless communication. Mayo regional hospital implements
      a state-of-the art wireless communications system.

PMID- 21739810
TI  - Automating sterile supply departments protects patients. A robotics company
      specializing in medical applications suggests that hospitals can benefit from
      lessons learned in lean manufacturing.

PMID- 21739811
TI  - Improving patient prep. An automated informed consent tool provides
      individualized pre-procedure patient instructions to thousands of veterans in the
      tri-state VA Gulf Coast Veterans Health Care System.

PMID- 21739812
TI  - EHR benefits in action. How leveraging actionable knowledge will strengthen
      public health efforts.

PMID- 21739813
TI  - A message from the Editor-in-Chief.

PMID- 21739814
TI  - Achieving environmental excellence through a multidisciplinary grassroots
      movement.
AB  - St. Joseph's Healthcare Hamilton (SJHH) supports a grassroots green team, called
      Environmental Vision and Action (EVA). Since the creation of EVA, a healthy
      balance between corporate projects led by corporate leaders and grassroots
      initiatives led by informal leaders has resulted in many successful environmental
      initiatives. Over a relatively short period of time, environmental successes at
      SJHH have included waste diversion programs, energy efficiency and reduction
      initiatives, alternative commuting programs, green purchasing practices, clinical
      and pharmacy greening and increased staff engagement and awareness. Knowledge of
      social movements theory helped EVA leaders to understand the internal processes
      of a grassroots movement and helped to guide it. Social movements theory may also
      have broader applicability in health care by understanding the passionate
      engagement that people bring to a common cause and how to evolve sources of
      opposition into engines for positive change. After early successes, as the
      limitations of a grassroots movement began to surface, the EVA team revived the
      concept of evolving the grassroots green program into a corporate program for
      environmental stewardship. It is hard to quantify the importance of allowing our
      staff, physicians, volunteers and patients to engage in changes that they feel
      passionately about. However, at SJHH, the transformation of a group of people
      unsatisfied with the organization's environmental performance into an 'engine for
      change' has led to a rapid improvement in environmental stewardship at SJHH that
      is now regarded as a success.

PMID- 21739815
TI  - Second wave reform in Alberta.
AB  - Alberta Health Services formally came into existence on April 1, 2009,
      potentially signaling the start of a new wave of health restructuring in Canada.
      This article situates that change in the context of international trends in
      health restructuring and reviews some of the challenges faced by the new
      organization.

PMID- 21739816
TI  - An interprofessional collaborative practice model: primary-care clinical
      associates at the family practice setting.
AB  - A persistent physician shortage challenges the ability of our healthcare system
      to meet the growing health needs of our aging population. Health system redesign
      must maximize the efficient use of available human resources. The Alberta
      Westview Primary Care Network (WPCN) introduced the Primary Care Clinical
      Associate (CA) program in 2005. This interprofessional collaborative practice
      model recruits nonphysician health professionals from various disciplines as
      autonomous, independent practitioners. They are associates of the family
      physician and use their full scope of practice to jointly care for a panel of
      patients in family practice settings. Three years after its inception, the CA
      program has grown steadily from two initial participating family practices to its
      current implementation in six of seven WPCN clinics. The present direction of
      Canadian primary healthcare reform is towards team approaches. Accordingly, the
      CA program has wide applicability provincially across Canada. The objective of
      this article is to describe in detail the design of the WPCN CA program including
      its conceptual framework and operational strategies and to share program
      implementation learning. This knowledge transfer will enable replication of the
      WPCN CA model, where appropriate, in other jurisdictions.

PMID- 21739817
TI  - Getting the right information to the table: using technology to support evidence
      based decision making.
AB  - Healthcare executives report that it is difficult to access the research
      literature and once found, it is frequently not relevant. A study was conducted
      to explore ways in which healthcare executives, enrolled in the EXTRA program,
      used a virtual desktop environment. Despite some design and function limitations,
      the desktop was perceived positively by most participants and was effective in
      supporting evidence-informed practice and decision making.

PMID- 21739818
TI  - A study of the effectiveness of performance-focused methodology for improved
      outcomes in Alberta public healthcare.
AB  - This study evaluates the effectiveness of a performance-focused methodology for
      engaging multidisciplinary, frontline healthcare teams in making behavioural
      changes that improve patient care and health system efficiency. Results include
      significant declines in average length of stay in hospital and waiting time for
      surgery, and a dramatic increase in early patient ambulation. Performance-focused
      methodology using key performance indicators, targets, measurement, and ongoing
      feedback, supported by non-monetary incentives, can quickly improve healthcare
      outcomes.

PMID- 21739819
TI  - Ethical challenges in a military-deployed operational setting.

PMID- 21739820
TI  - A message from the Editor-in-Chief.

PMID- 21739821
TI  - Institutional vicarious liability for physicians: have we reached the tipping
      point?
AB  - Historically, physicians were solely responsible for patient care, whereas
      hospitals merely provided equipment and nursing staff. Despite significant
      changes in the doctor-hospital relationship, Canadian courts maintain that
      physicians are independent contractors. This article explores whether proposals
      to tie remuneration to performance, increased board or management involvement in
      privileging, and shared accountability for quality between physicians, boards,
      and other providers will prompt the courts to shift to hospital vicarious
      liability for physician negligence.

PMID- 21739822
TI  - The breast cancer hormone receptor retesting controversy in Newfoundland and
      Labrador, Canada: lessons for the health system.
AB  - The treatment of newly diagnosed breast cancer patients with hormonal treatment
      is determined by the presence of estrogen receptor and progesterone receptor
      status in breast cancer. In Newfoundland and Labrador (NL), 425 of 1088 (39.1%)
      patients who had original "negative" receptor tests conducted between 1997 and
      2005, had positive results upon retesting in a specialized laboratory. This
      commentary addresses (1) the diagnostic utility of estrogen and progesterone
      testing for breast cancer in general, (2) specific testing problems that occurred
      in NL, (3) scientific problems associated with retesting, and (4) the impact on
      public trust and the resulting legal and political responses that occurred as a
      result of the adverse events associated with false-negative hormone receptor
      tests. Finally, the lessons learned will be discussed including known high false
      negative rates associated with the tests and the bias associated with retesting,
      the need for quality assurance and national standards, public education, and
      appropriate communication with patients and the public.

PMID- 21739823
TI  - Real numbers tell real stories in health services management.
AB  - In the words of one hospital manager, "hospital data is currently indigestible
      and alien to the average user." Drawing upon the experience of an academic
      hospital that, contrary to established practice, published real numbers alongside
      rates and ratios during a Clostridium difficile outbreak, the authors examined
      the pitfalls of publishing only abstract performance measures and the advantages
      of releasing real numbers to the public. This article identifies lessons for
      hospital board governance, media relations, employee communications, and citizen
      and patient engagement that are applicable across the healthcare industry in many
      countries. If healthcare is to be a caring industry, then care should be taken in
      the public reporting of data and information.

PMID- 21739824
TI  - Sustaining leadership in an unsustainable system.
AB  - Healthcare executive failures and departures are not only linked to the involved
      individuals' skills but also are often the result of complex dynamics reflecting
      larger system, societal, and global polarities and tensions. At the root of many
      of the challenges leaders face is system unsustainability. This article discusses
      common challenges as fractals of more complex dynamics, strategies for managing
      dynamics between organizations and their stakeholders, and approaches for leaders
      to sustain themselves within this unsustainable system.

PMID- 21739825
TI  - Achieving full compliance with standards for assertive community treatment
      programs in Ontario: does sponsoring agency type matter?
AB  - Assertive Community Treatment (ACT) programs provide community-based services for
      individuals with severe mental illness. In Ontario, these programs are funded by
      the Ministry of Health and Long-Term Care and administered through sponsoring
      agencies (hospitals, mental health facilities, and "other" community-based
      organizations). This article reports on the results of a survey of ACT programs
      and investigates the relationship between sponsoring agency type and ACT program
      operations. Findings and implications for policy makers and administrators are
      discussed.

PMID- 21739826
TI  - The role of mentorship and innovation: personal perspective.

PMID- 21739827
TI  - The strategic importance of relationships and tools for decision making.

PMID- 21739828
TI  - Real goals, real solutions.

PMID- 21739830
TI  - One peak at a time.

PMID- 21739829
TI  - My dysfunctional love affair with dental insurance.

PMID- 21739831
TI  - What they did not teach you in dental school.

PMID- 21739832
TI  - Be careful who and what you are recording.

PMID- 21739833
TI  - Leveraging your value.

PMID- 21739834
TI  - AAE and AAOMR joint position statement. Use of cone-beam-computed tomography in
      endodontics.
AB  - All radiographic examinations must be justified on an individual needs basis
      whereby the benefits to the patient of each exposure must outweigh the risks. In
      no case may the exposure of patients to X-rays be considered "routine", and
      certainly CBCT examinations should not be done without initially obtaining a
      thorough medical history and clinical examination. CBCT should be considered an
      adjunct to two-dimensional imaging in dentistry. Limited field of view CBCT
      systems can provide images of several teeth from approximately the same radiation
      dose as two periapical radiographs, and they may provide a dose savings over
      multiple traditional images in complex cases.

PMID- 21739836
TI  - Making things happen on PDA's social network forums.

PMID- 21739835
TI  - The QE2.

PMID- 21739837
TI  - A dentist for the ages. Interview by Jay Cohen.

PMID- 21739838
TI  - A message from the Editor-in-Chief.

PMID- 21739839
TI  - Knowledge to action: integrating the use of evidence in management decision
      making.
AB  - This article describes an intervention project focused on laying the foundation
      for the integration of evidence in management decision making in a home
      healthcare organization. The current state and readiness for change were
      assessed, revealing barriers and enablers to using evidence in decision making.
      Strategies were developed and implemented to address the barriers. Practical
      steps are outlined to assist other healthcare organizations wishing to embark on
      the journey of integrating evidence in management decision making.

PMID- 21739840
TI  - Improving the management of waiting lists for long term care.
AB  - Initially prepared for the South East Local Health Integration Network in
      Ontario, this literature review focuses on interventions to improve the
      management of waiting lists for admission to long-term care facilities. The
      review identified studies relating to four types of interventions: (1) different
      models for prioritizing patients, (2) ways to improve the accuracy of waiting
      lists, (3) the use of alternative care settings, and (4) altering the level of
      home care.

PMID- 21739841
TI  - A comparative cost-minimization analysis of providing paediatric palliative
      respite care before and after the opening of services at a paediatric hospice.
AB  - A palliative care service provider may add or decrease overall operational costs
      to the healthcare system. This study assessed the costs of managing respite care
      for children with life-limiting illness at the Children's Hospital of Eastern
      Ontario for the 12-month period both before and after services at Roger's House
      (RH, a paediatric hospice) was made available. The opening and operation of RH
      for providing respite care resulted in a minimization of operational costs (n =
      66 patients, mean decrease of $4,251.95 per month per patient).

PMID- 21739843
TI  - Global climate change and our health.

PMID- 21739842
TI  - Values and virtue.

PMID- 21739844
TI  - How sick is sick?

PMID- 21739845
TI  - A shifting paradigm. Hospitalists: a growing specialty in Arkansas.

PMID- 21739846
TI  - A new Arkansas resource for pediatric mental health.

PMID- 21739847
TI  - A stomachache can be a pain to the rear.

PMID- 21739848
TI  - Bradycardia: an important physical finding in anorexia nervosa.
AB  - Cardiovascular complications are common in patients with anorexia nervosa, an
      eating disorder resulting in severe malnutrition that affects multiple organ
      systems. Sinus bradycardia is the most common cardiovascular physical finding and
      the most common arrhythmia in patients with anorexia nervosa. It is important to
      appreciate the significance of sinus bradycardia in this clinical setting because
      it may be associated with sudden death, especially in the presence of other
      arrhythmias or EKG abnormalities, such as prolongation of the QTc interval. Since
      sinus bradycardia can occur in up to 95% of patients with anorexia nervosa, its
      clinical correlation with more lethal arrhythmias cannot be overemphasized.
      Physicians must be aware of the common cardiac findings on the physical
      examination of a patient with anorexia nervosa in order to refer those patients
      to tertiary care centers for treatment by eating disorder specialists.

PMID- 21739849
TI  - Distressed physicians.

PMID- 21739850
TI  - Patient's page. February is National Children's Dental Health month.

PMID- 21739851
TI  - Strengthening the backbone of our financial systems.

PMID- 21739852
TI  - Mediation review. A free public service sponsored by the Oklahoma Dental
      Association.

PMID- 21739853
TI  - I know I am, I'm sure I am, I'm H.A.P.P.Y.

PMID- 21739854
TI  - Building local plans: the early implementers.

PMID- 21739855
TI  - Bringing it back.

PMID- 21739856
TI  - Baby-led weaning: transitioning to solid foods at the baby's own pace.
AB  - Baby-led weaning is an approach to the introduction of solid foods that is being
      followed by increasing numbers of parents, but what is it, and should health
      visitors be encouraging it? This paper aims to refresh practitioners' background
      knowledge of complementary feeding and to outline the key features of baby-led
      weaning, as well as to explore the evidence that supports this approach as a
      logical adjunct to the move to six months for the introduction of solid foods.
      The more common concerns of parents and professionals, such as choking and iron
      intake, are addressed. Tips for implementing baby-led weaning are included and
      some of the potential benefits identified.

PMID- 21739857
TI  - Health visitors' experiences of child health promotion policy reform in England.
AB  - Child health promotion services in England have been revolutionised in the last
      decade, with a shift from a low-threshold universal service to a more highly
      targeted programme. This has affected health visitors' preventive healthcare work
      with families. This paper draws on findings from the qualitative arm of a mixed
      methods study that aimed to explore how child health promotion reform has been
      implemented. The particular focus of this paper is on health visitors'
      experiences of the process of policy reform. In-depth semi-structured telephone
      interviews were conducted with 25 health visitors working in urban areas in
      England, and data were analysed thematically. Health visitors described policy
      change as being enforced, but views on the new programme were coloured by the
      extent to which practitioners retained the autonomy to offer a service according
      to their professional judgment. Where practitioners retained professional
      autonomy, services were adequately staffed and there was a functional working
      environment, then interviewees were positive about child health promotion reform.
      Where health visitors felt they could not offer an appropriate level of health
      promotion services, they had grave concerns about the impact on child public
      health.

PMID- 21739858
TI  - An organisation-wide approach to training community practitioners in
      breastfeeding.
AB  - A new self-study training programme was delivered to community practitioners as
      part of an organisation-wide breastfeeding training programme. Knowledge outcomes
      were measured before and after the training using the Coventry University
      Breastfeeding Assessment. Interviews with participants found the programme was
      well received and seen as a key way to ensure consistent evidence-based practice.
      Practitioners across all professional groups increased knowledge scores after
      training. Independent evaluation showed that self-study is flexible and
      acceptable, but requires self-motivation as well as basic computer skills and
      access. Self-study is potentially more affordable, and could provide a means to
      regularly refresh the knowledge of staff and bring new recruits to the same
      objectively assessed standard. Recommendations include the use of learning sets
      to encourage team learning, and the production of a combined web and hard copy
      programme came from the learning achieved by piloting this new programme.

PMID- 21739859
TI  - Use of domperidone to enhance lactation: what is the evidence?
AB  - A perception of low milk supply is often cited as a reason to stop breastfeeding,
      though most mothers can produce more than enough with the right support and
      information. Domperidone may be used to promote lactation, and there is evidence
      to support its use. However, the many non-pharmacological ways in which a mother
      may be supported should be tried before considering domperidone.

PMID- 21739860
TI  - Diagnosis and assessment of food allergy in children and young people.
AB  - Food allergies are recognised as a major paediatric health problem in Western
      countries, affecting 6% to 8% of children up to the age of three years. Food
      allergy symptoms can be very severe or subtle and sometimes overlooked. Following
      a Department of Health review of allergy services in 2006, the National Institute
      for Health and Clinical Excellence (NICE) was commissioned to produce a guideline
      to support GPs and other healthcare professionals in primary care and community
      settings in recognising the signs and symptoms of food allergy in order to bring
      about consistency in diagnosis and assessment. This paper has been written by a
      member of the guideline development group to provide an overview of the guidance.
      The guidance addresses six key clinical questions about taking an allergy-focused
      clinical history, signs and symptoms of IgE-mediated and non-lgE mediated
      allergy, information and support that should be offered during the assessment
      process, when to refer on to secondary or specialist services, and the value of
      alternative allergy tests.

PMID- 21739861
TI  - New vision for the profession.

PMID- 21739862
TI  - After the elections.

PMID- 21739863
TI  - Great readers.

PMID- 21739864
TI  - American College of Dentists: an overview.
AB  - The American College of Dentists (ACD) is the oldest national-level honorary
      organization for dentists. Its members have exemplified excellence through
      outstanding leadership and exceptional contributions to dentistry and society.
      The ACD is nonprofit and apolitical, and has long been regarded as the
      "conscience of dentistry." The ACD has a record of involvement in a wide range of
      activities related to its mission and has played a vital role in positively
      shaping the profession and oral health care.

PMID- 21739865
TI  - International College of Dentists-USA Section: a brief history, 1934-2011.
AB  - Inspiration for the International College of Dentists can be traced to a Tokyo
      dinner in 1920, with the College being founded in 1927 and the USA Section
      following in 1934. The College has always held a focus on international relations
      and service. The USA Section has also developed a firm commitment to leadership.
      The origins of the College are traced in this article, and the organizational
      structure and a sampling of its many programs are also presented.

PMID- 21739866
TI  - The Academy of Dentistry International.
AB  - The Academy of Dentistry International was founded to promote the art and science
      of dentistry, especially through research and continuing education. Its mission
      is international in the sense of promoting exchange and service. The
      organizational structure of ADI is discussed as well as its membership. A
      defining characteristic of the Academy is an array of programs around the world
      supported by the Academy of Dentistry International Foundation.

PMID- 21739867
TI  - Omicron Kappa Upsilon: a historical and current perspective.
AB  - Founded by G. V. Black at Northwestern Dental School in 1914, Omicron Kappa
      Upsilon is the "Phi Beta Kappa" of dentistry, honoring students, faculty members,
      and honorary members for academic excellence and professional character. In
      addition, the honor society has a history of granting recognition of schools and
      individuals who have distinguished themselves and show promise for advancing
      dental education.

PMID- 21739868
TI  - Dental students choosing licensure path give more consideration to career
      flexibility rather than ethical dilemmas.
AB  - Although a patient-based clinical licensure examination (CLE) has been used in
      the United States for many decades to evaluate an individual's competency to
      practice dentistry, there continue to be validity, reliability, and ethical
      issues of concern to the profession. As a result of a 2009 decision by the
      Minnesota Board of Dentistry, dental students from the University of Minnesota
      School of Dentistry, beginning with the Class of 2010, are eligible for initial
      licensure in Minnesota by passing the nonpatient-based National Dental Examining
      Board of Canada Examination. Surveys were distributed to 101 senior dental
      students to assess what factors students used to decide whether or not to
      register for a patient-based CLE. The response rate to the survey was 84.2%
      (85/101). The opportunity to apply for a license in multiple states after passing
      a patient-based CLE was the primary factor in influencing the students to
      register for a patient-based CLE. Regarding the use of live patients in a CLE,
      students were most concerned with having to operatively restore teeth that could
      be treated more conservatively and for other reasons outside of their control,
      such as the patient failing to show up, patient not being accepted by the
      examiners, and procedural issues during the examination.

PMID- 21739869
TI  - A case of collegial communication and a patient who does not pay.
AB  - Four individuals who teach ethics in dental schools comment on a case in which
      negative financial information is revealed by one dentist when transferring
      records of a potential patient to another dentist. All commentators find varying
      degrees of ethical problem with disclosing such information. Professional codes
      discourage this practice. All commentators stress the importance of the potential
      new dentist developing a relationship based on professional standards, with the
      greatest emphasis placed on the patient's health needs. Several of the
      commentators discuss positive ways of conducting a patient interview, including
      specific useful language.

PMID- 21739870
TI  - Decision making.
AB  - A decision is a commitment of resources under conditions of risk in expectation
      of the best future outcome. The smart decision is always the strategy with the
      best overall expected value-the best combination of facts and values. Some of the
      special circumstances involved in decision making are discussed, including
      decisions where there are multiple goals, those where more than one person is
      involved in making the decision, using trigger points, framing decisions
      correctly, commitments to lost causes, and expert decision makers. A complex
      example of deciding about removal of asymptomatic third molars, with and without
      an EBD search, is discussed.

PMID- 21739871
TI  - Practicing the TEAM concept in all dental settings.

PMID- 21739872
TI  - How to flourish during an economic downturn.

PMID- 21739873
TI  - Stand taller for posture month.

PMID- 21739874
TI  - Education and career enhancement.

PMID- 21739875
TI  - Staff meetings: Their impact on dental practices.

PMID- 21739877
TI  - Quo vadis?

PMID- 21739876
TI  - Assembly and clinical use of the XCP-ORA: a three-function dental X-ray film
      positioning device for taking anterior and posterior periapical and bitewing
      intraoral radiographs.
AB  - This article describes the assembly and clinical use of a newer type ofXCP dental
      X-ray film positioning device, called the XCP-ORA. The previous version of the
      XCP consists of three separate devices for taking anterior, posterior, and
      bitewing radiographs. The XCP-ORA dental X-ray film holder combines all three of
      these dental X-ray functions into one device, in contrast to theprevious
      generation ofXCP holders. The large paralleling ring of the device contains three
      color-coded square-shaped holes that attach to a metal rod. This single metal rod
      with two right angle bends contains two sets of corresponding color-coded prongs
      that attach the anterior, posterior and bitewing X-ray film holders. One set of
      prongs consists of two red prongs that correspond to the insertion points of the
      bitewing X-ray film holder. The other set of prongs consists of one prong that is
      yellow colored, and another prong that is blue colored. Both of these prongs fit
      into the insertion holes of either the yellow (posterior) or the blue (anterior)
      film holders. The multi-function XCP-ORA device reduces the total number of XCP
      parts that are needed to take intraoral dental radiographs. Fewer parts make the
      device less confusing to assemble and reduce the number of steps that are needed
      to prepare the XCP-ORA parts for autoclaving.

PMID- 21739878
TI  - A messy way to nationalize healthcare.

PMID- 21739879
TI  - Is friday the busiest for late preterm delivery?
AB  - BACKGROUND: As a level Illc NICU serving north central West Virginia, we have
      observed that many of our admissions of infants GA 33-37 weeks occurred on
      Friday. OBJECTIVE: To investigate the distribution of delivery days for infants
      with GA between 33-37 wk. DESIGN/METHODS: Data of admitted infants are tracked
      through medical record from January 2002 to September 2006. The deliveries per
      day of the week (DOW) were compared. RESULTS: Of 1471 admission, the highest rate
      of delivery occurring on Fridays; lowest on Sundays. An unequal distribution of
      delivery DOW in infant GA 33-35 was observed, with the highest rate of delivery
      occurring on Wednesday. An unequal distribution of delivery DOW was also noted in
      infants with GA 36-37. However, Friday was noted as the most frequent DOW for
      delivery in this group. CONCLUSIONS: This Friday delivery phenomenon suggests
      delivery practices that may affect premature delivery, their morbidity and
      increased NICU occupancy.

PMID- 21739880
TI  - Correlation between MRCP and ERCP findings at a tertiary care hospital.
AB  - BACKGROUND: It is common clinical practice to obtain Magnetic Resonance
      Cholangiopancreatography (MRCP) prior to Endoscopic Retrograde
      Cholangiopancreatography (ERCP) to evaluate the biliary system. With recent
      improvements of MRCP, it is important to correlate the findings of these two
      studies. AIM: To examine the correlation between MRCP and ERCP findings in
      patients at a tertiary care hospital. METHODS: A total of 165 patients were
      identified who underwent MRCP prior to ERCP at West Virginia University between
      July 1, 2004 and June 30, 2006 (98 females and 67 males). Patients' demographic
      information and their laboratory values and diagnostic study outcomes prior to
      procedure were collected, entered into MS Access, and analyzed using SAS 10.0.
      Sensitivity, specificity, positive predictive value and negative predictive value
      were calculated. Two-tailed p-values of <= 0.05 were considered statistically
      significant. RESULTS: Baseline demographic characteristics were comparable
      between male and female patients. Hepatobiliary and pancreatic duct results were
      grouped together. MRCP was 74.6% sensitive and 83.5% specific for
      choledocholithiasis, 85.4% sensitive and 87.4% specific for strictures, 85.9%
      sensitive and 91.2% specific for obstruction, 92.4% sensitive and 93.5% specific
      for ductal dilatation, and 90.8% sensitive and 92.6% specific for detection of
      periductal masses. MRCP appeared to have more false negative results for
      choledocholithiasis and strictures and more false positive results for ductal
      dilatation and periductal mass detection compared with ERCP. CONCLUSIONS: In
      patients with presentations suggestive of hepatobiliary and pancreatic disease,
      despite recent improvements in MRCP technique, the sensitivity and specificity of
      MRCP is still not close enough to that of ERCP for detection of
      choledocholithiasis, hepatobiliary and pancreatic ductal dilatation, periductal
      masses, or obstruction to be used as a substitute. Thus, ERCP remains the gold
      standard for visualization of the hepatobiliary and pancreatic tree.

PMID- 21739881
TI  - An estimate of meperidine usage in West Virginia hospitals.
AB  - PURPOSE: Meperidine (Demerol) is a synthetic opiate that has been utilized for
      decades. Nonetheless, its safety and efficacy profile relative to other opiates
      have led many to advocate against its use. We attempted to estimate current usage
      of meperidine by hospitals in West Virginia. METHODS: Pharmacists at each
      hospital in West Virginia were surveyed by telephone. They were asked to estimate
      meperidine use as a proportion of all opiates used in their hospital. They were
      also queried about usage patterns and for the presence of any documented
      restrictions on the use of meperidine. RESULTS: 64% of hospitals in West Virginia
      report low usage of meperidine (<10% of all opiates). Of those hospitals with
      meperidine available on formulary, 47% reported the presence of documented
      policies or practices designed to limit meperidine usage. When used, meperidine
      is most commonly administered in connection with surgical procedures.
      CONCLUSIONS: Many West Virginia hospitals are limiting meperidine usage, in
      apparent accordance with guideline recommendations. However, traditional patterns
      of usage for certain indications remain.

PMID- 21739882
TI  - Jack.

PMID- 21739883
TI  - Fraternity.

PMID- 21739884
TI  - Learning from the 2009 H1N1 pandemic and looking forward.

PMID- 21739885
TI  - Partnership for patients: 'it's about time', say quality experts.
AB  - CMS to invest $1 billion in quality, safety initiatives and collaborations.
      Stakeholders, CMS should offer consistent messages about performance. Reducing
      preventable harm, re-admissions are two main goals.

PMID- 21739887
TI  - Using behavior, not vital signs, to assess pain.

PMID- 21739886
TI  - "Critical conversations" important in care process.
AB  - Discharge seen as highest-risk non-procedural part of care process. Staff were
      encouraged to come up with solutions. EMRs present a challenge for these types of
      tools.

PMID- 21739888
TI  - Staff-driven effort cuts door-to-doc time.

PMID- 21739889
TI  - New standards address patient communications.

PMID- 21739890
TI  - Program guides seniors through EOL process.

PMID- 21739891
TI  - Advocating means being a good steward.

PMID- 21739892
TI  - Factors associated with quit attempts and quitting among Eastern Hungarian women
      who smoked at the time of pregnancy.
AB  - INTRODUCTION: The purpose of this research was to assess factors associated with
      quit attempts and successful smoking cessation among a sample of
      socioeconomically disadvantaged pregnant women living in Eastern Hungary.
      MATERIALS AND METHODS: In-person interviews were conducted among 201 women
      residing in Eastern Hungary who self-identified as occasional or regular smokers
      at the time they learned they were pregnant. RESULTS: 54% of the women were
      smokers at the time they learned they were pregnant. Just over half tried to
      quit, but only 20% were successful. Factors associated with reduced likelihood of
      quit attempts included being a regular (vs. occasional) smoker (OR = 0.36, 95% CI
      0.13-1.00) and being Roma (vs. non-Roma) (OR = 0.32, 95% CI 0.14-0.72). Women who
      completed high school were 7% times more likely to quit (OR = 7.5, 95% CI 1.68
      33.2) and those who were employed were 7% times more likely to quit (OR = 7.6,
      95% CI 1.88-30.35). Regular smokers were 88% less likely to quit than occasional
      smokers. DISCUSSION: Smoking cessation interventions targeting pregnant women are
      needed in Eastern Hungary. Efforts to integrate smoking cessation into the
      current excellent pre-natal care and health visitor program will reach most women
      who are pregnant or who have given birth within the preceding 3 years.

PMID- 21739893
TI  - The prevalence of cigarette smoking and its relation to certain risk predictors
      of cardiovascular diseases in central-Slovakian Roma children and adolescents.
AB  - The objective of the study was to determine some Cardiovascular Disease (CVD)
      risk factors in relation to cigarette smoking in 174 Roma children and
      adolescents (88 males and 86 females) and 131 non-Roma probands (males and
      females) aged 7-18 in central Slovakia. In this biethnic study, 26.4% of the Roma
      children and adolescents (more than twice contrary to the control group) were
      smokers. Among the studied ethnicities, the majority of smokers was Roma (79.3%,
      46 subjects). Smoking Roma have higher means of TG, Lp(a) and WHR compared with
      non-smoking non-Roma. The most frequent CVD risk predictors of smoking Roma
      probands was low serum levels HDL-C, apo A (the Fisher test confirmed a
      significant relationship between cigarette smoking and HDL-C, apo A; p < 0.01).
      The results of the research should help to develop an effective preventative
      health education programs focused on Roma education (who live in a higher-risk
      environment compared to the majority population) in order to stem the spread of
      CVD as well as morbidity and mortality in this ethnic group living in Slovakia.

PMID- 21739894
TI  - Many countries hit by health threats from both infectious and chronic diseases
      new data site makes WHO data and analyses widely available.

PMID- 21739895
TI  - Tobacco advertisements targeted on women: creating an awareness among women.
AB  - It has been always believed that men smoke more than women, but the trend of
      smoking in women is increasing nowadays. In some countries there are even more
      female smokers than male smokers. This is a major health risk because women are
      present and future mothers, and increasing number of smoking women will enlarge
      the number of exposed children. Relatively few women are aware of gender-specific
      health risks, including cervical cancer, osteoporosis, poor pregnancy outcome and
      early menopause. Tobacco related diseases are on the rise in women, considering
      the fact that more women now die of lung cancer than breast cancer. Tobacco
      companies have invented various ways to target women through tobacco advertising
      despite the various bans. This inevitably leads to the increase in female smoking
      rates. There are various recommendations from the World Health Organization which
      include the need for governments to pay particular attention to protect women
      from the tobacco companies' attempts to lure them into lifetimes of nicotine
      dependence and to take up counter advertisements against the tobacco companies.

PMID- 21739896
TI  - Short risk behaviour knowledge index for HIV average risk population of sexual
      active age in Munich, Germany.
AB  - PURPOSE: A short HIV/AIDS risk behaviour knowledge index based on questions about
      HIV transmission and prevention of HIV infection during sexual intercourse and
      intravenous drug use is proposed and implemented for an HIV average risk
      population in Munich. METHODS: Knowledge levels about HIV/AIDS risk behaviour was
      assessed in a group of people (n = 210) in sexually active age range of 18-49
      years which was at an average risk of contracting HIV. Four questions about HIV
      transmission by unprotected vaginal, anal, or oral sexual intercourse, and by
      needle sharing, and two questions about HIV prevention by condom use, and the
      single use of needles and syringes were chosen from ten others for making a four
      level risk behaviour knowledge index (HIV/AIDS Transmission through Sex and
      Intravenous Drug Use, HATSIDU) internally consistent according to Cronbach's
      alpha. RESULTS: HATSIDU index (mean 3.0, SD +/- 1.18) was not associated (p>0.05)
      with sex and marital status, but depended (p < 0.05) on age, education and social
      status. General population of Munich in a sexually active age group of 40-49
      years, or those without further education or the unemployed, had a significantly
      lower knowledge of HIV risk behaviour. CONCLUSION: The HATSIDU is a simple and
      usable index for the assessment of HIV/AIDS risk behaviour knowledge in a
      population with an average risk of HIV infection.

PMID- 21739897
TI  - Syphilis among STD clinic patients in Prague in 2009.
AB  - The aim of the study was to evaluate clinical, epidemiological and demographic
      data of patients with syphilis hospitalized at the Department of
      Dermatovenereology of the General Teaching Hospital in 2009 and to identify the
      groups at high risk of sexually transmitted diseases. The results were compared
      with the previous surveys carried out between 1999 and 2005 and also with the
      data of the National Registry of Venereal Diseases for 2008. A total of 232
      patients were hospitalized in 2009 (including 26 women admitted for compulsory
      retreatment in pregnancy). We noticed a 25% increase in the number of patients in
      comparison with the year 2008. Of the total number of patients, 206 were patients
      with newly diagnosed syphilis, of which 153 (74.3%) were men and 53 (25.7%)
      women. There was 22.3% of patients with primary and 31.6% with secondary
      syphilis. As in the previous years, heterosexual contact remained the most
      frequent route of syphilis transmission. However, the number of homosexual and
      bisexual men increased, amounting to 64.7% of all hospitalized men. Four men were
      HIV positive. The age distribution did not change; majority of the patients were
      aged between 30 and 40. The proportion of foreigners also remained unchanged
      (19.9%); they came mainly from the Slovak Republic (31.1%) and Ukraine (26.7%).
      The absolute number of reported syphilis cases has been increasing in the Czech
      Republic since 2006. From the epidemiologic point of view, the increasing
      incidence of early stages of the disease is alarming. Men prevail over women
      among the infected persons; the men having sex with men (MSM) has been increasing
      in the last three years.

PMID- 21739898
TI  - World Cancer Day 2011. New physical activity guidance can help reduce risk of
      breast, colon cancers.

PMID- 21739899
TI  - Barriers to care and current medical and social needs of HIV-positive patients in
      Albania.
AB  - OBJECTIVE: As HIV/AIDS prevalence rises in Eastern Europe, assessment of local
      epidemics in the bordering Central European region, especially South Eastern
      Europe, is vital in order to meet treatment and prevention needs. Understanding
      current medical and social needs and barriers to care experienced by HIV-positive
      patients in these regions may provide insight into how to best respond to the
      local epidemics, increase patients' access to treatment, and reduce loss to
      follow-up. DESIGN: This study assesses the patient characteristics, barriers to
      care, and current medical and social needs of HIV-positive patients in Albania.
      Semi-structured interviews were used in this cross-sectional study. METHODS: We
      interviewed 79 of 85 patients (93% response rate) followed at the University
      Hospital Center of Tirana (UHCT) HIV/AIDS Ambulatory Clinic, which represented
      the majority of patients under HIV care in Albania during 2009. RESULTS: The
      local HIV epidemic seems to be comprised mainly of heterosexual men who have
      spent an average of 3.6 years abroad. The vast majority of patients under care at
      UHCT HIV/AIDS Ambulatory Clinic had experienced barriers to care associated with
      social stigma (97.4%), lack of knowledge of HIV medical care (76.6%), and medical
      provider's lack of knowledge of HIV (70.9%). Social needs of the patients were
      also overwhelmingly unmet (90.0-95.7%). CONCLUSIONS: In addressing HIV/AIDS in
      Albania, it will be crucial to educate the healthcare sector in ways to identify
      and address barriers to care and current medical and social needs of HIV-positive
      patients.

PMID- 21739900
TI  - Vaccination of patients with diabetes mellitus--a retrospective study.
AB  - 402 subjects with diabetes mellitus have been vaccinated of the total of 34,000
      vaccinees immunized during the study period of 9 and half months. Altogether 229
      diabetic patients (56.97%) have been vaccinated'against tick-borne encephalitis
      (TBE) and 74 (18.4%) against viral hepatitis (41 types A+B, 30 type A, 3 type B).
      The average age in four most commonly administered vaccines (FSME IMMUN 0.5 ML,
      Twinrix Adult, Typhim Vi, and Havrix 1440) was 65, 52, 56, and 54 years,
      respectively. Live attenuated vaccines have been given to 6 patients with
      diabetes (1.49%)--- 5 travellers to endemic countries received the yellow fever
      vaccine Stamaril (1 female, 4 male) and one male patient varicella vaccine
      Varilrix. Among the least common vaccines in diabetic patients were those against
      invasive pneumococcal and meningococcal infections. Not a single unexpected side
      effect has been observed following the vaccination procedure in any diabetic
      patient. Based on the results of this retrospective study we can conclude that
      vaccination in diabetic patients is free of any ri-k- provided that there are no
      other contraindications, e.g. allergy to vaccine components or severe acute
      febrile illness. In the case of unstable glycaemia and significantly impaired
      immune system due to diabetes mellitus, vaccination with live attenuated vaccines
      should be carefully considered and measured against the risks of exposure to each
      and every specific infectious agent. There is no reason to be afraid of
      vaccination in diabetic patients provided that general contraindications are
      respected. On the contrary, this risk group can benefit from vaccination more
      remarkably since it may have some life-saving potential.

PMID- 21739901
TI  - Turkey joins International Agency for Research on Cancer.

PMID- 21739902
TI  - Nutritional status and growth parameters of school-age Roma children in the
      Republic of Macedonia.
AB  - Main objective of the study was to assess the nutritional status of school age
      Roma children in Macedonia in order to detect precursors of possible health risks
      at an early age. The study was designed as a comparative case control study.
      Study group consisted of 229 Roma school children from the 1st and 272 from the
      5th grade residing in different towns in Macedonia. The control group was
      recruited from other than Roma ethnic background and consisted of 283 children
      attending 1st and 356 children attending 5th grade. Every participant was
      measured for his/hers body height and weight. The t-test and Chi square (Chi2)
      were applied to test statistical significance of variables. The WHO's AnthroPlus
      software was applied to assess growth parameters and population at risk. There
      were significant differences in values of the body weight (p = 0.001) and height
      (p = 0.001) between Roma and non-Roma children attending the 1st grade of primary
      school. Weight-for-age, height-for-age and BMI-for-age indexes of the 1st grade
      children significantly differred in in the same intervals of SD (> or = -2SD and
      < -1SD; > or = -1SD and median; > +1SD and < or = +2SD; between Roma and non-Roma
      5th graders. Anthropometric parameters of nutritional status of Roma children in
      Macedonia are significantly different than those of their non-Roma peers. Their
      health risks are predominantly related to underweight. The parameters related to
      health risks of overweight or obesity are lower in Roma than in non-Roma
      children.

PMID- 21739903
TI  - Problem of substance misuse and lack of national strategy in Kosovo.
AB  - The aim of this project was to explore the problem of substance misuse among
      adolescent town dwellers in Kosovo, as a result of lack of a national strategy
      related to this problem. DESIGN: 261 students from 4 secondary schools took part
      in cross sectional survey performed in October 2005. The survey was carried out
      in Gjilan town in south-east of Kosovo. MAIN RESULTS: From all questioned
      students, 36% smoked cigarettes every day, 12.6% consumed alcohol occasionally
      and 1.4% consumed all kind of drugs regularly. Girls consumed more cigarettes,
      whereas boys consumed more alcohol and other drugs. The prevalence of substance
      misuse was higher among students in their last year of high school attendance.
      Students in Gjilan continue to smoke, consume alcohol and drugs despite their
      knowledge about the adverse health consequences of substance misuse, but in the
      same time, most of them consider information and counselling the best way of
      substance misuse prevention. CONCLUSIONS: The prevalence and trends of substance
      misuse among students in our survey indicates that it is time to start acting. It
      is assumed that results of survey may be a very useful source of information for
      policy-makers, government and ministry of health in developing and implementing
      national strategy that would address the most important issues in connection with
      addiction among adolescents.

PMID- 21739904
TI  - New WHO report: deaths from noncommunicable diseases on the rise, with developing
      world hit hardest.

PMID- 21739905
TI  - Associations of subjective sleep quality with depression score, anxiety, physical
      symptoms and sleep onset latency in students.
AB  - OBJECTIVE: Sleep quality is strongly associated with parameters of mental and
      physical health and therefore a major public health issue. We wanted to evaluate
      this association in young and healthy students by a survey. Further, we aimed to
      detect the relevance of sleep onset latency and sleep duration for sleep quality.
      METHODS: A group of young nursing and technical students was surveyed (N = 196)
      with the objective to measure subjective sleep quality, sleep onset latency,
      sleep duration, depression score, physical symptoms, trait-anxiety, and
      pathological eating behaviours. RESULTS: Subjective sleep quality was strongly
      negative correlated with depression score (Pearson's r = -0.57), physical
      symptoms (r = -0.51) and trait-anxiety (r = -0.54) (p < 0.001 for all three).
      Subjective sleep quality's association with sleep onset latency was stronger than
      with sleep duration. Further, high depression score (odds ratio OR = 3.90; 95%
      confidence interval CI = 1.88-8.06) and long sleep onset latency (OR = 3.56; 95%
      CI = 1.65-7.69) were the best predictors of poor subjective sleep quality.
      CONCLUSIONS: This study supports evidence that links physical and mental symptoms
      with poor sleep quality. Especially important is the fact that we found this
      connection in young and basically healthy adults. Taking into account that poor
      sleep quality has major negative long term impact on health, prevention
      programmes should focus especially on the association between depressive symptoms
      and subjective sleep quality that is significantly influenced by sleep onset
      latency.

PMID- 21739906
TI  - Publication bias in epidemiological studies.
AB  - Communication of research findings is the utmost responsibility of all
      scientists. Publication bias occurs if scientific studies with negative or null
      results fail to get published. This can happen due to bias in submitting,
      reviewing, accepting, publishing or aggregating scientific literature that fails
      to show positive results on a particular topic. Publication bias can make
      scientific literature unrepresentative of the actual research studies. This can
      give the reader a false impression about the beneficial effects of a particular
      treatment or intervention and can influence clinical decision making. Publication
      bias is more common than it is actually considered to be, but there are ways to
      detect and prevent it. This paper comments on the occurrence, types and
      consequences of publication bias and the strategies employed to detect and
      control it.

PMID- 21739907
TI  - Frequency and characteristics of myocardial ischemia recorded during stress
      echocardiography in patients with high coronary risk.
AB  - BACKGROUND/AIM: Ischemic heart disease is the major cause of morbidity and
      mortality in the world as well as in our country. Ischemic heart disease has the
      multifactorial origin and the presence of several risk factors increases the risk
      of myocardial ischemia. The aim of the study was to evaluate the frequency and
      characteristics of myocardial ischemia in asymptomatic subjects with two or more
      risk factors for coronary artery disease during stress echocardiography. METHODS:
      In 240 high risk asymptomatic subjects (an absolute risk of fatal cardiovascular
      disease of more than 5%, according to the Systemic Coronary Risk Evaluation
      Chart), the exercise stress echocardiography test was performed. The criterion
      for myocardial ischemia was the appearance of transient segmental wall motion
      abnormality (WMA). The wall motion score index was calculated before and after
      the exercise stress echocardiography. RESULTS: During exercise stress
      echocardiography, in 36 (15%) subjects WMA occurred. Out of 36 subjects with
      myocardial ischemia, in 10 (27.8%) subjects WMA and ST segment depression were
      accompanied with the first occurrence of chest pain (the subgroup with
      symptomatic myocardial ischemia), in 20 (55.6%) subjects WMA and ST segment
      depression were detected and in 6 (16.6%) subjects only WMA occurred (the
      subgroup with silent myocardial ischemia). There were no significant differences
      between the subgroups with symptomatic and silent myocardial ischemia with regard
      to exercise tolerance, heart rate at the onset of WMA, and time to the onset of
      WMA, but the wall motion score index was significantly higher in the subjects
      with symptomatic myocardial ischemia (p < 0.01). In all the individuals with
      symptomatic myocardial ischemia, significant stenosis of the coronary arteries
      was found by coronary angiography. Out of 26 subjects with asymptomatic
      myocardial ischemia, coronary angiography was performed in 18 and significant
      stenosis of the coronary arteries was diagnosed in all of them. The number and
      grade of coronary stenosis in subjects with symptomatic and silent myocardial
      ischemia were similar. CONCLUSION: The obtained results presented the incidence
      of myocardial ischemia in 15% of asymptomatic subjects with high coronary risk
      during stress echocardiography. Silent myocardial ischemia was markedly more
      frequent than symptomatic one, but in the subjects with symptomatic ischemia, the
      wall motion score index was significantly higher.

PMID- 21739908
TI  - Unstable intertrochanteric fractures: how to prevent uncontrolled impaction and
      shortening of the femur.
AB  - BACKGROUND/AIM: Unstable intertrochanteric (IT) fractures, especially fractures
      with a reverse or transverse fracture line, have tendencies to make significant
      impaction on shortening of the femoral neck and lower extremity. The
      biomechanical complexity of the fracture, the type and the position of the
      implant are known to influence postoperative outcome. The aim of this study was
      to compare characteristics of two versions of dynamic hip implants in controlling
      the dynamization of unstable IT fractures of the femur. METHODS: In the
      prospective study that included 1,115 patients with fractures of the proximal
      femur, 61 patients had IT fractures with a reverse or transverse fracture line.
      All the patients were treated surgically with the same implant in two versions:
      Dynamic Hip Screw - DHS-MB-S implant with a rigid part of standard length (40 mm)
      and DHS-MB-I implant, with a rigid part of the implant individualized for each
      patient depending on the transverse diameter of the proximal femur. The patients
      were under gradual radiographic and clinical control. Six months postoperatively
      we measured the length of the extremity and the degree of the medialization of
      the distal part of the femur. RESULTS: All the fractures healed six months after
      the operation. Medialization and shortening of the extremity were significantly
      less in the group with fractures fixed by the DHS-MB-I implant, in which length
      of the rigid part of the implant was preoperatively measured individually for
      each patient. CONCLUSION: In order to achieve a desired functional result, the
      control of dynamisation in unstable IT fractures is significant in the fixation
      of these fractures of the femur. We presented possible methods to realize it by
      the contact of the rigid part of our implant with medial cortex of the proximal
      fragment of the femur.

PMID- 21739909
TI  - Multislice computed tomography urography in the diagnosis of urinary tract
      diseases.
AB  - BACKGROUND/AIM: . Multislice computed tomography (MSCT) has triggered
      considerable changes in uroradiological imaging. The aim of this study was to
      establish the place of MSCT urography (MSCTU) in comparison with intravenous
      urography (IVU) and to determine the sensitivity and specificity of MSCT in the
      evaluation of urothelial abnormalities. METHODS: This prospective study included
      120 patients with a high clinical suspicion of urinary tract diseases divided
      into two groups. The group I consisted of 60 patients with macroscopic hematuria,
      bladder carcinoma and malignant pelvic tumors after radiotherapy or operation.
      They underwent both IVU and MSCTU. The group II included 60 patients (> or = 40
      years old) with retroperitoneal and malignant pelvic tumors, complicated
      pyelonephritis, microscopic hematuria, acute urinary tract obstruction (without
      visible calculi on unenhanced scans), and they were submitted to computed
      tomography with additional scan phase enabling MSCTU. RESULTS: Compared with IVU,
      MSCTU is more sensitive for the detection of urinary tract diseases (parenchymal
      changes, renal tumors, urolithiasis, fibrosis) and extraurinary processes. MSCTU
      is more specific than IVU for renal parenchymal abnormalities, tumors of the
      excretory system, urolithiasis, bladder tumors, fibrosis and extraurinary
      diseases. MSCTU is equally sensitive, but more specific for hydronephrosis
      compared to MSCT. The diagnosis made by the use of MSCTU in patients with
      macroscopic and microscopic hematuria and with obstruction not caused by stones,
      perfectly comply with operative findings and histological diagnosis. CONCLUSION:
      The obtained results support MSCTU to be the modality of choice in the diagnostic
      algorithm of patients with macroscopic hematuria and in the evaluation of
      microscopic hematuria and unexplained obstruction of the urinary tract. The only
      remaining role for IVU in our institution is imaging of the upper urinary tract
      in patients with hematuria under the age of 40.

PMID- 21739910
TI  - Color Doppler ultrasonography and multislice computer tomography angiography in
      carotid plaque detection and characterization.
AB  - BACKGROUND/AIM: Cerebrovascular diseases are the third leading cause of mortality
      in the world, following malignant and cardiovascular diseases. Therefore, their
      timely and precise diagnostics is of great importance. The aim of this study was
      to compare duplex scan Color Doppler ultrasonography (CDU) with multislice
      computed tomography angiography (MSCTA) in detection of morphological and
      functional disorders at extracranial level of carotid arteries. METHODS: The
      study included 75 patients with 150 carotid arteries examined in the period from
      January 2008 to April 2009. The patients were firstly examined by CDU, then
      MSCTA, followed by the surgery of extracranial segment of carotid arteries. In 10
      patients, the obtained material was referred for histopathological (HP)
      examination. We used both CDU and MSCT in the analysis of: plaque surface, plaque
      structure, degree of stenosis, and the presence of in-traplaque hemorrhage.
      RESULTS: The results obtained by CDU and MSCTA were first compared between
      themselves, and then to intraoperative findings. Retrospective analysis showed
      that MSCTA is more sensitive than CDU in assessment of plaque surface (for smooth
      plaques CDU 89%: MSCTA 97%; for plaques with irregular surface CDU 75% : MSCTA
      87%; for ulcerations CDU 54%: MSCTA 87%). Regarding determination of plaque
      structure (mixed plaque CDU 66% : MSCTA 70%; correlation with HP findings CDU 94%
      : MSCTA 96%) and localization (CDU 63%: MSCTA 65%), and in terms of sensitivity
      and specificity, both methods showed almost the same results. Also, there is no
      statistical difference between these two methods for the degree of stenosis (CDU
      96%: MSCTA 98%). CONCLUSION: Atherosclerotic disease of extracranial part of
      carotid arteries primarily affects population of middle-aged and elderly, showing
      more associated risk factors. Sensitivity and specificity of CDU and MSCTA
      regarding plaque composition, the degree of stenosis and plaque localization are
      almost the same. These results and the fact that there are no adverse effects
      (high radiation dose) compared to MSCTA indicate that CDU should be the initial
      method in diagnostic algorythm for carotid arteries.

PMID- 21739911
TI  - Cytokines in pathogenesis of peri-implantitis.

PMID- 21739912
TI  - Response to cladribine in patient with systemic mastocytosis.
AB  - INTRODUCTION: Systemic mastocytosis is a heterogeneous group of hematological
      disorders characterized by accumulation of mast cells in different organs. CASE
      REPORT: A 41-year-old woman presented with a three-year history of fatigue,
      occasional diarrhea, mild fever, skin rash and splenomegaly. Laboratory results
      showed severe anemia and thrombocytopenia. Cytological and histological
      investigation of bone marrow showed a marked increase of mast cells infiltration
      with following immunophenotype: CD117+, CD68+, CD34-, MPO-, CD15-. She was
      treated with cladribine 0.15 mg/kg body weight from day 1 to day 5, a total of
      six cycles, and achieved a good partial response, transfusion independency and
      normalization of spleen size. Although the patient responded to the treatment,
      the relapse with splenomegaly and bicytopenia was observed after 10 months.
      CONCLUSION: Cladribine therapy was efficient in the patient' with systemic
      mastocytosis but the response was transient, so there is the need to search for
      new therapeutic options and more effective strategies in the treatment of
      patients with aggressive mast cell disorders.

PMID- 21739913
TI  - Familial aggregation of bladder cancer.
AB  - Except for smoking and certain occupational exposures, the etiology of bladder
      cancer is largely unknown. Several case reports have described familial
      aggregation of transitional cell carcinoma of the bladder. Although the majority
      of patients with bladder cancer do not have family history of transitional cell
      carcinoma of the urinary tract, the study of familial transitional cell carcinoma
      may lead to the knowledge on the pathogenesis of this disease. The purpose of
      this study was to describe three cases of urinary bladder cancer in a single
      three-member family, i.e. in two generations (mother and son) and a family member
      related by marriage (the patient's wife). CASE REPORT: Three cases of urinary
      bladder cancer occurred in a three-member family within the interval of 5 years.
      The following common characteristics were detected in our patients: old age (over
      60), working as farmers for more than 50 years, negative personal medical history
      on relevant health disorders, place of birth--village, place of residence-
      village, the same water supply, similar nutrition, positive family history on
      urinary bladder cancer or other malignant tumors, the first sign of illness was
      macroscopic hematuria in all the patients and the same pathohistological type of
      cancer--carcinoma papillare transitiocellulare. CONCLUSION: The stated common
      characteristics in our cases indicate, above all, the impact of exposure to
      external surrounding factors on the occurrence of urinary bladder cancer.

PMID- 21739914
TI  - Hashimoto's encephalopathy: a long-lasting remission induced by intravenous
      immunoglobulins.
AB  - BACKGROUND: Hashimoto's encephalopathy (HE) is a rare autoimmune syndrome
      characterized by various neuropsychiatric manifestations, responsive to steroid
      treatment and associated with Hashimoto's thyroiditis. There are only a few
      reports suggesting that intravenous immunoglobulins (IVIG) might represent an
      efficacious treatment modality for the severe steroid-resistant HE cases. We
      presented a patient with HE who developed a complete recovery after the IVIG
      therapy followed by a long-lasting remission. CASE REPORT: We described herien a
      female patient with the one-year history of autoimmune thyroiditis before the
      development of neuropsychiatric manifestations. In May 1999, a 38-year-old woman
      presented at the Institute of Neurology, Clinical Center of Serbia, Belgrade,
      with the brain-stem syndrome which responded well to steroid treatment. After
      detailed examinations, the diagnosis of Hashimoto's encephalopathy was
      established. Two years later, in June 2001, new manifestations (unsteadiness in
      gait, personality changes, seizures, and persistent headache) gradually developed
      during a 6-month period. Response to steroids was unsatisfactory and partial,
      since headaches and personality changes had continuously worsened. In January
      2002, the patient received IVIG (0.4 g/kg body weight daily for 5 days). Gradual
      improvement was noticed and a complete recovery developed over the following
      weeks. Up to March 2009, during a 7-year follow-up period, remission persisted.
      CONCLUSION: To our best knowledge, this is the first report of a long-lasting
      remission of Hashimoto's encephalopathy after IVIG therapy. Therefore, this case
      further supports administration of IVIG, as a potentially beneficial treatment
      modality, in severe cases of Hashimoto's encephalopathy which are completely or
      partially resistant to steroids.

PMID- 21739915
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy.
AB  - INTRODUCTION: Fast and precise diagnostics of the disease from the large group of
      adult leukoencephalopathy is difficult but responsible job, because the outcome
      of the disease is very often determined by its name. Cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is
      caused by the mutation of Notch 3 gene on chromosome locus 19p13. Beside the
      brain arterioles being the main disease targets, extracerebral small blood
      vessels are affected by the pathological process. Clinically present signs are
      recurrent ischemic strokes and vascular dementia. CADASIL in its progressive form
      shows a distinctive pattern of pathological changes on MRI of endocranium. The
      diagnosis is confirmed by the presence of granular osmiophilic material (GOM) in
      histopathological skin biopsies. CASE REPORTS: Two young adult patients
      manifested ischemic strokes of unknown etiology, cognitive deterioration,
      migraine and psychopathological phenomenology. MRI of endocranium pointed on
      CADASIL. Ultrastructural examination of skin biopsy proved the presence of GOM in
      the basal lamina and near smooth muscle cells of arteriole dermis leading to
      CADASIL diagnosis. The presence of GOM in histopathological preparation is 100%
      specific for CADASIL. The patients were not searched for mutation in Notch 3 gene
      on chromosome 19, because some other leukoencephalopathy was disregarded.
      CONCLUSION: Suggestive clinical picture, distinctive finding of endocranium MRI,
      the presence of GOM by ultrastructural examination of histopathological skin
      biopsies are sufficient to confirm CADASIL diagnosis.

PMID- 21739917
TI  - E-prescribing grows quickly, suffers from data problems.

PMID- 21739916
TI  - IPAB likely to put pressure on Medicare Advantage & Part D.

PMID- 21739918
TI  - Pharmacists test payment model based on outcomes.

PMID- 21739919
TI  - Onerous regulations put ACOs on ropes.

PMID- 21739920
TI  - Payers step in with 'real-world' comparative effectiveness research.

PMID- 21739921
TI  - Casting a wider net.

PMID- 21739922
TI  - Pursuing a bang for the buck in the battle of the bulge.

PMID- 21739923
TI  - Plans breathe life into COPD efforts.

PMID- 21739924
TI  - Health care costs associated with treatment modification in type 2 diabetes
      mellitus patients taking oral anti-diabetic drugs.
AB  - OBJECTIVES: To compare health care costs among patients with type 2 diabetes
      mellitus (T2DM) who added a new oral anti-diabetes drug (OAD) to an initial
      regimen with those who up-titrated their initial OAD. METHODS: Insurance claims
      data were obtained from 94 health plans for patients aged >=18 years with ICD-9
      CM diagnosis of T2DM during the period Jan. 1, 2001-June 30, 2007, and a newly
      prescribed metformin or sulfonylurea monotherapy. Patients were followed after
      initiating monotherapy to identify occurrence of first-treatment modification
      (addition or up-titration). Health care costs were analyzed during 360 days after
      first treatment modification. Subgroup analyses included comparison of addition
      cohort with two titration subgroups: 1) titration up to or below intermediate
      doses and 2) titration to beyond intermediate doses. RESULTS: During the post
      treatment modification period, all-cause medication costs were 9% higher (p <
      0.0001), while inpatient costs were 14% lower for the addition cohort (p < 0.008)
      as compared to the up-titration cohort. The total risk-adjusted health care costs
      were slightly lower but statistically insignificant for the addition cohort
      compared to the up-titration cohort (ratio of cost = 0.99; p = 0.052). These
      costs patterns remained similar for both the up-titration subgroups. CONCLUSIONS:
      While addition of another OAD to the initial OAD regimen may result in higher
      medication costs, the lower inpatient costs and overall offset in the subsequent
      total costs may indicate clinical benefits with the add-on treatment. When
      appropriate and clinically beneficial, physicians may want to consider adding an
      OAD rather than up-titrating the current OAD, particularly beyond intermediate
      dose levels.

PMID- 21739925
TI  - Government payers shouldering more Rx payments.

PMID- 21739926
TI  - PBM effort takes cue from reform, market.

PMID- 21739928
TI  - Medical cost trend for 2012 to hit 8.5 percent.

PMID- 21739927
TI  - New prostate cancer drug encourages development of treatment pathway.

PMID- 21739929
TI  - Locust bean gum as superdisintegrant--formulation and evaluation of nimesulide
      orodispersible tablets.
AB  - Orodispersible tablets disperse instantaneously in the mouth so that they can be
      swallowed without the aid of water. The aim of the present study was to formulate
      nimesulide orodispersible tablets using locust bean gum as a natural
      superdisintegrant. The gum was evaluated for powder flow properties, swelling
      index and loss on drying. Excellent powder flow properties were observed,
      swelling index was found to be 20 which indicated appreciable capability of
      locust bean gum to be used as superdisintegrant. The prepared tablets were
      evaluated against standard superdisintegrant i.e. cross-carmellose sodium.
      Disintegration time of tablets containing 10 % locust bean gum was found to be 13
      seconds. The prepared batches were also evaluated for wetting time, water
      absorption ratio, effective pore radius, porosity, in vitro and in vivo
      disintegration time, in vitro release and stability studies. Wetting time was
      found to reduce from 19 +/- 2 to 11 +/- 3 sec (A1-A4) and 51 +/- 2 to 36 +/- 3
      sec (B1-B4). Effective pore radius and porosity were found to be increase with
      increase in polymer concentration. The superdisintegrant property of locust bean
      gum may be due to concentration dependent wicking action leading to formation of
      porous structure which disintegrates the tablet within seconds. In-vivo results
      were complementary to in-vitro disintegration time results. The in-vitro release
      studies were compared against marketed nimesulide fast dissolving tablets
      (Nimulid MD). Stability studies showed that there was no significant change in
      hardness, friability, tensile strength and assay of the prepared formulations.
      The f2 values (in comparison with Nimulid MD) of 92.27 and 98.19 were obtained
      with A3 and A4 batches respectively.

PMID- 21739930
TI  - Influence of internal optical astigmatism on the correction of myopic astigmatism
      by LASIK.
AB  - PURPOSE: To investigate the influence of the origin of astigmatism on the
      correction of myopic astigmatism by LASIK. METHODS: A retrospective study was
      conducted of the records of 192 patients (192 eyes) undergoing LASIK for
      correction of myopia and myopic astigmatism from January to September 2010.
      Ocular residual astigmatism (ORA) and lenticular astigmatism (LA) were determined
      by vector analysis using objective refraction and Pentacam (Oculus Optikgerate
      GmbH) imaging of both corneal surfaces. Patients were divided into two groups
      according to ORA (high ORA group: ORA/preoperative refractive astigmatism >1;
      normal ORA group: ORA/preoperative refractive astigmatism <= 1) and LA (high LA
      group: LA/preoperative refractive astigmatism >1; normal LA group:
      LA/preoperative refractive astigmatism <= 1). Procedural efficacy was compared
      between those eyes with and without a significant amount of internal optical
      astigmatism using index of success. RESULTS: Mean preoperative vectors for the
      astigmatism of the anterior cornea, posterior cornea, and lens were -1.33 * 3.0
      degrees , -0.33 * 95.3 degrees , and -0.27 * 103.3 degrees , respectively. Mean
      indices of success in the high and low ORA groups were 1.75 and 0.59,
      respectively (t=7.81, P<.001). Mean indices of success in the high and low LA
      groups were 2.07 and 0.70, respectively (t=12.36, P<.001). The higher indices of
      success in the high ORA and high LA groups suggest a lower efficacy of LASIK in
      treating astigmatism primarily located intraocularly. CONCLUSIONS: Myopic LASIK
      is less effective in correcting astigmatism when astigmatism is mainly located at
      the internal optics. Topography and refractive value should be incorporated in
      the treatment of patients when a significant amount of internal optical
      astigmatism is detected preoperatively.

PMID- 21739931
TI  - Long-term results of phakic refractive lens implantation in eyes with high
      myopia.
AB  - PURPOSE: To evaluate the long-term results of phakic refractive lens (PRL; Carl
      Zeiss Meditec) implantation in eyes with high myopia. METHODS: In this
      retrospective, noncomparative, interventional case series, 143 myopic eyes of 82
      patients were treated for high myopia with the implantation of the silicone PRL
      in the posterior chamber. RESULTS: Mean follow-up was 3.8+/-1.7 years (range: 1
      to 6 years). Six years postoperatively (n=34), a statistically significant
      reduction was noted in the cycloplegic spherical equivalent from -14.08+/-4.00
      diopters (D) (range: -24.88 to -4.75 D) before PRL implantation to -0.45+/-0.62 D
      (range: -1.00 to 1.00 D) (P<.001). At 6 years, 67.6% (23 eyes) and 91.2% (31
      eyes) were within +/-0.50 and +/-1.00 D of target refraction, respectively. Mean
      logMAR uncorrected and corrected distance visual acuity improved significantly
      (P<.001) (counting fingers preoperatively in all eyes to 0.17+/-0.15 [range: 0.54
      to -0.06] and 0.19+/-0.19 [1.00 to -0.08] to 0.07+/-0.10 [range: 0.30 to -0.10],
      respectively). Complications included anterior capsule damage (3 eyes), temporary
      intraocular pressure increase (14 eyes), pigment dispersion (1 eye), and PRL
      decentration (1 eye). No eyes presented any signs of cataract up to 6 years
      postoperatively. CONCLUSIONS: Long-term results show that PRL implantation is an
      effective and safe method for treating high myopia.

PMID- 21739932
TI  - Wild and farm breeding cervids infections with Anaplasma phagocytophilum.
AB  - The main goal of our study was to determine the prevalence of Anaplasma
      phagocytophilum infections in wild cervids living in north-eastern part of
      Poland. Material used in the study was gathered between the years 2004- 2008. The
      blood samples from 106 red deer (Cervus elaphus), 32 sika deer (Cervus nippon
      hortulorum), 130 fallow deer (Dama dama) and 31 roe deer (Capreolus capreolus)
      were collected. DNA was isolated using Genomic Mini AX blood kit (A and A
      Biotechnology). Molecular detection of A. phagocytophilum was based on nested PCR
      amplification of a species-specific 16S rRNA fragment gene of A. phagocytophilum.
      The highest prevalence of infection was detected in Cervus elaphus, Capreolus
      capreolus, Cervus nippon hortulorum, there were 50.9 percent, 38.7 percent, 34.37
      percent of infected animals, respectively. The lowest rate of infection was found
      in fallow deer (Dama dama) - ony 1.5 percent.

PMID- 21739933
TI  - Polybrominated diphenyl ethers, polychlorinated biphenyls and organochlorine
      pesticides in human milk as markers of environmental exposure to these compounds.
AB  - This study aimed at the generation of preliminary results allowing for the
      assessment of breastfed infants exposure to polybrominated diphenyl ethers
      (PBDEs) which constitute important contaminants in places of human habitation.
      The second goal was to compare the concentrations of these compounds with other
      contaminants which people are exposed to via food chain. 28 breast milk samples
      from women living in Warsaw and neighbourhood were analyzed for polybrominated
      diphenyl ethers (BDE-47, BDE-99, BDE-153), polychlorinated biphenyls (CB-77, CB
      101, CB-118, CB-126, CB- 138, CB-153, CB170, CB-180) and organochlorine
      pesticides (HCB, beta-HCH, gamma-HCH, p,p'-DDE, p,p'-DDD, p,p'-DDT). The SigmaDDT
      levels noted in our studies were higher than in other European countries. The
      concentrations of the examined polychlorinated biphenyls and polybrominated
      diphenyl ethers did not diverge from the levels presented by other authors and
      are comparable to the levels noted in other countries in Europe.

PMID- 21739934
TI  - Antimicrobial activity of two essential oils.
AB  - The aim of the study was to evaluate the antimicrobial activity of essential oils
      in vitro for possible application to reduce the content of microorganisms in the
      air of animal houses. The essential oils of Cymbopogon citrarus L. and Malaleuca
      alternifolia L. were screened against bacteria Staphylococcus aureus,
      Enterococcus faecium, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis
      and yeast Candida albicans. The minimal inhibitory concentration of the active
      essential oils was tested using broth dilution assay. The essential oils
      concentrations ranged from 0.1-50.0%. The combined effects of essential oils were
      tested for Malaleuca alternifolia L. and Cymbopogon citrarus L. concentrations
      ranged from 0.005-50.0%. The oils showed a wide spectrum of antibacterial
      activity. Concentrations of 0.1-0.5% of Cymbopogon citrarus L. and Malaleuca
      alternifolia L. reduced total microorganisms count of Proteus mirabilis and
      Candida albicans. High antibacterial activity was also revealed for Cymbopogon
      citrarus L. with bactericidal concentrations of 0.8% for Escherichia coli, 5.0%
      for Enterococcus faecium, 5.0% for Pseudomonas aeruginosa and 8.0% for
      Staphylococcus aureus. Bactericidal concentrations of Malaleuca alternifolia L.
      were 5.0% for Pseudomonas aeruginosa and Enterococcus faecium, and 8.0% for
      Staphylococcus aureus. The essential oils of Cymbopogon citrarus and Malaleuca
      alternifolia may be a promising alternative of air disinfection in animal houses.

PMID- 21739935
TI  - Synthesis and pharmacological characterization of bicyclic triple reuptake
      inhibitor 3-aryl octahydrocyclopenta[c]pyrrole analogues.
AB  - The present work expands the chemical space known to offer potent inhibition of
      the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine
      transporter (DAT) and discloses novel bicyclic octahydrocyclopenta[c]pyrrole and
      octahydro-1H-isoindole scaffolds as potent triple reuptake inhibitors (TRIs) for
      the potential treatment of depression. Optimized compounds 22a (SERT, NET, DAT,
      IC(50) = 20, 109, 430 nM), 23a (SERT, NET, DAT, IC(50) = 29, 85, 168 nM), and 26a
      (SERT, NET, DAT, IC(50) = 53, 150, 140 nM) were highly brain penetrant, active in
      vivo in the mouse tail suspension test at 10 and 30 mpk PO, and were not
      generally motor stimulants at doses ranging from 1 to 30 mpk PO. Moderate in
      vitro cytochrome P450 (CYP) and potassium ion channel Kv11.1 (hERG) inhibition
      were uncovered as potential liabilities for the chemical series.

PMID- 21739936
TI  - Insights into the effects of functional groups on carbon nanotubes for the
      electrooxidation of methanol.
AB  - Functionalized carbon nanotubes were used as a support for PtCo nanoparticles.
      Their performance as electrocatalysts for the electrooxidation of methanol was
      evaluated by cyclic voltammetry and in situ FTIR reflectance spectroscopy. The
      onset potentials for both the electrooxidation of methanol and the production of
      CO(2) shifted to less positive values for catalysts prepared with more oxygen
      groups on the support. Furthermore, the production of CO(2) was higher on
      catalysts prepared with functionalized carbon nanotubes. The functional groups
      play two different but complementary roles. On the one hand, they help to
      stabilize smaller PtCo particles of ca. 3 nm. On the other hand, they provide the
      -OH groups necessary for the total oxidation of methanol to CO(2) at potentials
      less positive than on nonfunctionalized supports. Remarkably, the consumption of
      carboxylic acid groups along with the production of water is observed in the
      infrared spectra of the functionalized supports recorded during the
      electrooxidation of methanol. This observation suggests that the -OH groups of
      the support can also react with methanol, forming water and an ester.

PMID- 21739939
TI  - En route to osmium analogues of KP1019: synthesis, structure, spectroscopic
      properties and antiproliferative activity of trans-[Os(IV)Cl4(Hazole)2].
AB  - By controlled Anderson type rearrangement reactions complexes of the general
      formula trans-[Os(IV)Cl(4)(Hazole)(2)], where Hazole = 1H-pyrazole, 2H-indazole,
      1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-indazole
      tautomer stabilization in trans-[Os(IV)Cl(4)(2H-indazole)(2)] is unprecedented in
      coordination chemistry of indazole. The metal ion in these compounds possesses
      the same coordination environment as ruthenium(III) in
      (H(2)ind)[Ru(III)Cl(4)(Hind)(2)], where Hind = 1H-indazole, (KP1019), an
      investigational anticancer drug in phase I clinical trials. These osmium(IV)
      complexes are appropriate precursors for the synthesis of osmium(III) analogues
      of KP1019. In addition the formation of an adduct of trans-[Os(IV)Cl(4)(Hpz)(2)]
      with cucurbit[7]uril is described. The compounds have been comprehensively
      characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy
      (IR, UV-vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their
      antiproliferative acitivity in the human cancer cell lines CH1 (ovarian
      carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is
      reported.

PMID- 21739938
TI  - Discovery of potent and selective inhibitors of human platelet-type 12-
      lipoxygenase.
AB  - We report the discovery of novel small molecule inhibitors of platelet-type 12
      human lipoxygenase, which display nanomolar activity against the purified enzyme,
      using a quantitative high-throughput screen (qHTS) on a library of 153607
      compounds. These compounds also exhibit excellent specificity, >50-fold
      selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human
      lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold
      selectivity vs ovine cyclooxygenase-1 and human cyclooxygenase-2. Kinetic
      experiments indicate this chemotype is a noncompetitive inhibitor that does not
      reduce the active site iron. Moreover, chiral HPLC separation of two of the
      racemic lead molecules revealed a strong preference for the (-)-enantiomers
      (IC(50) of 0.43 +/- 0.04 and 0.38 +/- 0.05 MUM) compared to the (+)-enantiomers
      (IC(50) of >25 MUM for both), indicating a fine degree of selectivity in the
      active site due to chiral geometry. In addition, these compounds demonstrate
      efficacy in cellular models, which underscores their relevance to disease
      modification.

PMID- 21739940
TI  - Electrosynthesis of substituted 1H-indoles from o-nitrostyrenes.
AB  - A novel procedure has been devised for the synthesis of derivatives of 1H-indole
      that is based on the direct, room-temperature electrochemical reduction of
      substituted o-nitrostyrenes at carbon cathodes in N,N-dimethylformamide
      containing tetramethylammonium tetrafluoroborate as supporting electrolyte and in
      the presence of a 10-fold molar excess of a proton donor (phenol or methyl 3
      oxobutanoate).

PMID- 21739941
TI  - S-alkylation of thiacalixarenes: a long-neglected possibility in the calixarene
      family.
AB  - Despite the high nucleophilicity of sulfur atoms, thiacalixarenes have been
      alkylated only on oxygen atoms thus far. Using strong alkylating agents
      (triflates, trialkyloxonium salts), the substitution of the sulfur bridges has
      been successfully accomplished. The corresponding sulfonium salts of
      thiacalix[4]arene are formed regio- and stereoselectively as a completely new
      type of substitution pattern in thiacalixarene chemistry. These compounds possess
      interesting conformational behavior and could be used as unusual alkylating
      agents with uncommon selectivity.

PMID- 21739942
TI  - Total synthesis of (-)-CP2-disorazole C1.
AB  - The total synthesis of a bis-cyclopropane analog of the antimitotic natural
      product (-)-disorazole C(1) was accomplished in 23 steps and 1.1% overall yield.
      A vinyl cyclopropane cross-metathesis reaction generated a key (E)-alkene segment
      of the target molecule. IC(50) determinations of (-)-CP(2)-disorazole C(1) in
      human colon cancer cell lines indicated low nanomolar cytotoxic properties.
      Accordingly, this synthetic bioisostere represents the first biologically active
      disorazole analog not containing a conjugated diene or polyene substructure
      element.

PMID- 21739943
TI  - Synthesis and optical properties of soluble near-infrared arylene
      bisthienoimidazole dyes.
AB  - Soluble, film-forming near-infrared arylene bisthienoimidazole dyes with a band
      gap of 1.2-1.3 eV are electrochromic and absorb strongly at the telecommunication
      wavelengths (1310 and 1550 nm) in the oxidized state.

PMID- 21739944
TI  - Electropolymerized self-assembled layer on gold nanoparticles: detection of
      inducible nitric oxide synthase in neuronal cell culture.
AB  - Novel nanostructures of gold nanoparticle (AuNP) encapsulated-conductive polymer
      have been developed to study biosensor probe materials and utilized to detect the
      concentration of inducible nitric oxide synthase (iNOS). A 2,2':5',5"
      terthiophene-3'-benzoic acid (TTBA) monomer was synthesized and self-assembled on
      gold nanoparticles (AuNPs). The size effects of the AuNPs and TTBA monomer film
      thickness on the electrode conductivity were examined. Anti-iNOS antibody was
      covalently bound on an encapsulated-AuNPs polymer layer with self-assembled TTBA.
      The immunocomplex formation between iNOS and anti-iNOS was directly observed by
      cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). This
      study looked at the applicability of the self-assembled TTBA layer where the
      results indicated an efficient electrochemical response toward iNOS. The
      calibration plot of the current response vs. iNOS concentration exhibited a
      linear relationship in the range of 0.001-0.02 MUg/mL. The calibration
      sensitivity of iNOS was 59.4 +/- 0.3 mV/MUg mL(-1). The detection limit of iNOS
      was determined to be 0.20 +/- 0.04 ng/mL based on five time measurements (95%
      confidence level, k = 3, n = 5). Further results show that AuNP-encapsulated
      conductive polymers are good nanostructured materials as biosensor probes and
      have a potential application in cell biosensors.

PMID- 21739945
TI  - Recognition properties of acyclic glycoluril oligomers.
AB  - The fragmentation reaction of bis-nor-seco-CB[10] with 3,5-dimethylphenol (3)
      delivers methylene bridged glycoluril pentamer 5 in 81% yield. The host-guest
      recognition properties of the previously known tetramer 4 and those of pentamer 5
      and hexamer 6 toward cationic guests in water are used to delineate some
      important features of the binding of acyclic CB[n]-type receptors.

PMID- 21739946
TI  - Molecular origins and consequences of High-800 LH2 in Roseobacter denitrificans.
AB  - Roseobacter denitrificans is a marine bacterium capable of using a wide variety
      of different metabolic schemes and in particular is an anoxygenic aerobic
      photosynthetic bacterium. In the work reported here we use a deletion mutant that
      we have constructed to investigate the structural origin of the unusual High-800
      light-harvesting complex absorption in this bacterium. We suggest that the
      structure is essentially unaltered when compared to the usual nonameric complexes
      but that a change in the environment of the C(13:1) carbonyl group is responsible
      for the change in spectrum. We tentatively relate this change to the presence of
      a serine residue in the alpha-polypeptide. Surprisingly, the low spectral overlap
      between the peripheral and core light-harvesting systems appears not to
      compromise energy collection efficiency too severely. We suggest that this may be
      at the expense of maintaining a low antenna size.

PMID- 21739947
TI  - Highly selective reactions of unbiased alkenyl halides and alkylzinc halides:
      Negishi-Plus couplings.
AB  - High yielding stereo- and chemoselective Pd-catalyzed cross-couplings in THF at
      room temperature of alkenyl iodides and bromides with primary and secondary alkyl
      zinc iodides have been developed with the aid of N-methyimidazole as the key
      additive.

PMID- 21739948
TI  - Ligand effects on Negishi couplings of alkenyl halides.
AB  - Negishi couplings at olefinic centers do not always occur with the anticipated
      maintenance of stereochemistry. The source of erosion has been traced to the
      ligand, and a modified method has been developed that solves the stereochemical
      issue and significantly improves yields of Negishi couplings in general.

PMID- 21739949
TI  - Highly regioselective intermolecular hydroacylations of enamides with
      salicylaldehydes.
AB  - Highly regioselective intermolecular hydroacylations of enamides under rhodium
      catalysis with monodentate phosphane ligands are reported for the first time. The
      presence of MeCN facilitates this novel C-C bond formation, and the electron
      deficient phosphine P(p-F-Ph)(3) has proven most effective for the direct
      hydroacylation of 1-vinyl-2-pyrrolidinone. Accordingly, an atom-economic
      synthetic route to alpha-amido ketones from readily available substrates has been
      developed.

PMID- 21739950
TI  - Efficient synthesis of beta-chlorovinylketones from acetylene in chloroaluminate
      ionic liquids.
AB  - A method for the Friedel-Crafts-type insertion reaction of acetylene with acid
      chlorides in chloroaluminate ionic liquids is presented. The use of ionic liquids
      not only serves to avoid the use of carbon tetrachloride or 1,2-dichloroethane
      but also suppresses side reactions, notably the polymerization of acetylene,
      which occurs in these chlorinated solvents. Consequently, the products can be
      isolated using a simpler purification procedure, giving a range of aromatic and
      aliphatic beta-chlorovinyl ketones in high yield and purity.

PMID- 21739951
TI  - Engineering photonic-plasmonic coupling in metal nanoparticle necklaces.
AB  - In this paper, by combining three-dimensional finite-difference time-domain
      simulations, dark-field scattering analysis, and surface-enhanced Raman
      spectroscopy (SERS) we systematically investigate the light-scattering and field
      localization properties of circular loops of closely spaced gold nanoparticles,
      or "nanoplasmonic necklaces", fabricated by electron-beam lithography on quartz
      substrates. In particular, we show that nanoplasmonic necklaces support two
      hybridized dipolar scattering resonances with polarization-controlled
      subwavelength localized fields (i.e., electromagnetic hot-spots), whose
      intensities are optimized by varying the necklace particle diameter and the
      particle number. Moreover, we show that strong field intensity enhancement is
      obtained for the particular necklace diameters where loop-localized photonic
      resonances efficiently couple to the broadband plasmonic modes, enabling a simple
      design strategy for the optimization of electromagnetic near-fields. Following
      the proposed approach, we design nanoplasmonic necklaces supporting stronger
      field intensity enhancement than traditional nanoparticle monomer and dimer
      arrays. Finally, by performing SERS experiments on nanoplasmonic necklaces coated
      with a pMA molecular monolayer, we validate the optimization of their near-field
      properties and demonstrate their potential for plasmon-enhanced spectroscopy and
      sensing.

PMID- 21739952
TI  - Synthesis of 5-iodo-1,2,3-triazole-containing macrocycles using copper flow
      reactor technology.
AB  - A new macrocyclization strategy to synthesize 12- to 31-membered 5-iodo-1,2,3
      triazole-containing macrocycles is described. The macrocycles have been generated
      using a simple and efficient copper-catalyzed cycloaddition in flow under
      environmentally friendly conditions. This methodology also permits the facile,
      regioselective synthesis of 1,4,5-trisubstituted-1,2,3-triazole-containing
      macrocyles using palladium-catalyzed cross-coupling reactions.

PMID- 21739953
TI  - Enhanced glutathione peroxidase activity of conformationally restricted
      naphthalene peri-dichalcogenides.
AB  - Conformationally restricted naphthalene peri-diselenides function as glutathione
      peroxidase mimetics with superior catalytic activity to that displayed by typical
      acyclic diaryl diselenides. Their activity was increased by electron-donating
      methoxy substituents, while a further 100-fold increase was observed with the
      corresponding ditelluride.

PMID- 21739954
TI  - Luminescence resonance energy transfer in the cytoplasm of live Escherichia coli
      cells.
AB  - Luminescence resonance energy transfer (LRET) offers many advantages for accurate
      measurements of distances between specific sites in living cells, but progress in
      developing a methodology for implementing this technique has been limited. We
      report here the design, expression, and characterization of a test protein for
      development of a LRET methodology. The protein, which we call DAL, contains the
      following domains (from the N-terminus): Escherichia coli dihydrofolate reductase
      (DHFR), the third and fourth ankyrin repeats of p16(INK4a), a lanthanide-binding
      tag (LBT), and a hexahistidine tag. LBT binds Tb(3+) with a submicromolar
      dissociation constant. LRET was measured from the Tb(3+) site on LBT to
      transition metals bound to the hexa-His tag and to fluorescein methotrexate bound
      to DHFR. The measured distances were consistent with a molecular model
      constructed from the known crystal structures of the constituent domains of DAL.
      The results indicate that the two C-terminal ankyrin domains of p16(INK4a) are
      stably folded when combined with other protein domains. We found that Tb(3+)
      binds to DAL in the cytoplasm of live E. coli cells, and thus, DAL is useful as
      an indicator for studies of metal transport. We also used DAL to measure LRET
      from Tb(3+) to Cu(2+) in the cytoplasm of live E. coli cells. The rates of Tb(3+)
      and Cu(2+) transport were not affected by a proton uncoupler or an ATP synthase
      inhibitor. Reversal of the membrane potential had a small inhibitory effect, and
      removal of lipopolysaccharide had a small accelerating effect on transport.
      Changing the external pH from 7 to 5 strongly inhibited the Tb(3+) signal,
      suggesting that the Tb(3+)-LBT interaction is useful as a cytoplasmic pH
      indicator in the range of approximately pH 5-6.

PMID- 21739956
TI  - Photoreactive surfactants: a facile and clean route to oxide and metal
      nanoparticles in reverse micelles.
AB  - A new class of photoreactive surfactants (PRSs) is presented here, consisting of
      amphiphiles that can also act as reagents in photochemical reactions. An example
      PRS is cobalt 2-ethylhexanoate (Co(EH)(2)), which forms reverse micelles (RMs) in
      a hydrocarbon solvent, as well as mixed reversed micelles with the standard
      surfactant Aerosol-OT (AOT). Small-angle neutron scattering (SANS) data show that
      mixed AOT/PRS RMs have a spherical structure and size similar to that of pure AOT
      micelles. Excitation of the ligand-to-metal charge transfer (LMCT) band in the
      PRSs promotes electron transfer from PRS to associated metal counterions, leading
      to the generation of metal and metal-oxide nanoparticles inside the RMs. This
      work presents proof of concept for employing PRSs as precursors to obtain nearly
      monodisperse inorganic nanoparticles: here both Co(3)O(4) and Bi nanoparticles
      have been synthesized at high metal concentration (10(-2) M) by simply
      irradiating the RMs. These results point toward a new approach of photoreactive
      self-assembly, which represents a clean and straightforward route to the
      generation of nanomaterials.

PMID- 21739957
TI  - RNA transcript 3'-proximal sequence affects translocation bias of RNA polymerase.
AB  - Translocation of RNA polymerase on DNA is thought to involve oscillations between
      pretranslocated and posttranslocated states that are rectified by nucleotide
      addition or pyrophosphorolysis. The pretranslocated register is also a precursor
      to transcriptional pause states that mediate regulation of transcript elongation.
      However, the determinants of bias between the pretranslocated and
      posttranslocated states are incompletely understood. To investigate translocation
      bias in multisubunit RNA polymerases, we measured rates of pyrophosphorolysis,
      which occurs in the pretranslocated register, in minimal elongation complexes
      containing T. thermophilus or E. coli RNA polymerase. Our results suggest that
      the identity of RNA:DNA nucleotides in the active site are strong determinants of
      susceptibility to pyrophosphorolysis, and thus translocation bias, with the 3'
      RNA nucleotide favoring the pretranslocated state in the order U > C > A > G. The
      preference of 3' U vs G for the pretranslocated register appeared to be universal
      among both bacterial and eukaryotic RNA polymerases and was confirmed by
      exonuclease III footprinting of defined elongation complexes. However, the
      relationship of pyrophosphate concentration to the rate of pyrophosphorolysis of
      3' U-containing versus 3' G-containing elongation complexes did not match
      predictions of a simple mechanism in which 3'-RNA seqeunce affects only
      translocation bias and pyrophosphate (PPi) binds only to the pretranslocated
      state.

PMID- 21739958
TI  - Synthesis of carbolines by photostimulated cyclization of anilinohalopyridines.
AB  - A general synthetic route to prepare all four carboline regioisomers by
      photostimulated cyclization of anilinohalopyridines is described. The methodology
      affords various substituted carbolines in good to excellent yields. In the case
      of alpha-carbolines, the S(RN)1 methodology complements previously reported
      palladium-catalyzed cyclization approaches.

PMID- 21739959
TI  - Temperature sensitivity trends and multi-stimuli sensitive behavior in
      amphiphilic oligomers.
AB  - A series of oligomers, containing oligo(ethylene glycol) (OEG) moieties, with the
      same composition of amphiphilic functionalities has been designed, synthesized,
      and characterized on the basis of their temperature-sensitive behavior. The non
      covalent amphiphilic aggregates, formed from these molecules, influence their
      temperature sensitivity. Covalent tethering of the amphiphilic units also has a
      significant influence on their temperature sensitivity. The lower critical
      solution temperatures of these oligomers show increasingly sharp transitions with
      increasing numbers of OEG functional groups, indicating enhanced cooperativity in
      dehydration of the OEG moieties when they are covalently tethered. These
      molecules were also engineered to be concurrently sensitive to enzymatic reaction
      and pH. This possibility was investigated using porcine liver esterase as the
      enzyme; we show that enzymatic action on the pentamer lowers its temperature
      sensitivity. The product moiety from the enzymatic reaction also gives the
      amphiphilic oligomer a pH-dependent temperature sensitivity.

PMID- 21739960
TI  - Cyclic imines: chemistry and mechanism of action: a review.
AB  - In recent years, there has been an increase in the production of shellfish and in
      global demand for seafood as nutritious and healthy food. Unfortunately, a
      significant number of incidences of shellfish poisoning occur worldwide, and
      microalgae that produce phycotoxins are responsible for most of these.
      Phycotoxins include several groups of small to medium sized natural products with
      molecular masses ranging from 300 to over 3000 Da. Cyclic imines (CIs) are a
      recently discovered group of marine biotoxins characterized by their fast acting
      toxicity, inducing a characteristic rapid death in the intraperitoneal mouse
      bioassay. These toxins are macrocyclic compounds with imine (carbon-nitrogen
      double bond) and spiro-linked ether moieties. They are grouped together due to
      the imino group functioning as their common pharmacore and due to the
      similarities in their intraperitoneal toxicity in mice. Spirolides (SPXs) are the
      largest group of CIs cyclic imines that together with gymnodimines (GYMs) are
      best characterized. Although the amount of cyclic imines in shellfish is not
      regulated and these substances have not been categorically linked to human
      intoxication, they trigger high intraperitoneal toxicity in rodents. In this
      review, the corresponding chemical structures of each member of the CIs and their
      derivatives are reviewed as well as all the data accumulated on their mechanism
      of action at cellular level.

PMID- 21739961
TI  - Biocatalytic organic synthesis of optically pure (S)-scoulerine and berbine and
      benzylisoquinoline alkaloids.
AB  - A chemoenzymatic approach for the asymmetric total synthesis of the title
      compounds is described that employs an enantioselective oxidative C-C bond
      formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step.
      This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline
      derivatives and (S)-berbines such as the natural product (S)-scoulerine, a
      sedative and muscle relaxing agent. The racemic substrates rac-1 required for the
      biotransformation were prepared in 4-8 linear steps using either a Bischler
      Napieralski cyclization or a C1-Calpha alkylation approach. The chemoenzymatic
      synthesis was applied to the preparation of fourteen enantiomerically pure
      alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and
      gave overall yields of up to 20% over 5-9 linear steps.

PMID- 21739962
TI  - Ordered nanopattern arrangement of gold nanoparticles on beta-sheet peptide
      templates through nucleobase pairing.
AB  - We have demonstrated a unique method for rational arrangement of gold (Au)
      nanoparticles on a beta-sheet peptide template through nucleobase pairing. For
      the template, the 16-mer peptide 1 was synthesized, which is based on an
      alternating amphiphilic sequence of Asp-Leu. Here Leu at the sixth position is
      replaced by thymine-modified Lys, and a polyethylene glycol chain is introduced
      to the C-terminus. The surface of Au nanoparticles was modified with the
      complementary adenyl group. Peptide 1 formed a stable beta-sheet monolayer at the
      air/water interface under an appropriate surface pressure. The monolayer film
      transferred onto a mica surface by the Langmuir-Blodgett method showed a linearly
      striped pattern with 6.1 nm average stripe width and 6 nm average interval
      between stripes, derived from beta-sheet assembly. The adenine-bound Au
      nanoparticles were successfully immobilized on the thymine-bound template through
      a complementary adenine-thymine hydrogen bonding pair. Interestingly, linear
      assembly structures of the Au nanoparticles were observed, thus being
      successfully reproduced by the original striped pattern of the template of 1. Our
      method might readily fabricate Au materials with our desirable 2D pattern through
      fine-tuning of beta-sheet sequence and nucleobase position.

PMID- 21739963
TI  - Supramolecular route to well-ordered metal nanofoams.
AB  - Metal nanofoams with a porosity above 50% v/v have recently attracted great
      interest in materials science due to their interesting properties. We demonstrate
      a new straightforward route to prepare such nanofoams using diblock copolymer
      based PS-block-P4VP(PDP) supramolecules that self-assemble into a bicontinuous
      gyroid morphology, consisting of PS network channels in a P4VP(PDP) matrix. After
      dissolving the PDP, the P4VP collapses onto the PS struts and a free-standing
      bicontinuous gyroid template of 50-100 MUm thickness and interconnected,
      uniformly sized pores is formed. The hydrophilic P4VP corona facilitates the
      penetration of water-based plating reagents into the porous template and enables
      a successful metal deposition. After plating, the polymer is simply degraded by
      heating, resulting in a well-ordered inverse gyroid nickel foam. Essential to
      this approach is the removal of only one part of the matrix (i.e., PDP).
      Therefore, the template accounts for 50% v/v or more. The porosity
      characteristics (amount, size of pores) can be tuned by selecting the appropriate
      copolymer and by adjusting the amount of PDP.

PMID- 21739964
TI  - Total synthesis of the antifungal depsipeptide petriellin A.
AB  - We report the solid-phase total synthesis of the antifungal highly modified
      cyclic depsipeptide petriellin A. The synthesis confirms earlier reports on the
      absolute configuration of the natural product. The solid-phase approach resulted
      in a protected linear precursor, which was cleaved from the solid support prior
      to cyclization and final deprotection. Use of advanced coupling agents for
      several hindered amides was a feature of the synthesis. The natural product was
      prepared in overall 5% yield.

PMID- 21739965
TI  - One-step fabrication of nanostructured Ni film with lotus effect from deep
      eutectic solvent.
AB  - We report a procedure to fabricate nanostructured Ni films via programmed
      electrochemical deposition from a choline-chloride-based ionic liquid at a high
      temperature of 90  degrees C. Three electrodeposition modes using constant
      voltage, pulse voltage, and reverse pulse voltage produce a variety of
      nanostructured Ni films with micro/nanobinary surface architectures, such as
      nanosheets, aligned nanostrips, and hierarchical flowers. The nanostructured Ni
      films possess face-centered cubic crystal structure. Amazingly, it is found that
      the electrodeposited Ni films deliver the superhydrophobic surfaces without any
      further modifications by low surface-energy materials, which might be attributed
      to the vigorous micro/nanobinary architectures and the surface chemical
      composition. The electrochemical measurements reveal that the superhydrophobic Ni
      film exhibit an obvious passivation phenomenon, which could provide enhanced
      corrosion resistance for the substrate in the aqueous solutions.

PMID- 21739966
TI  - Spider silk-based gene carriers for tumor cell-specific delivery.
AB  - The present study demonstrates pDNA complexes of recombinant silk proteins
      containing poly(L-lysine) and tumor-homing peptides (THPs), which are globular
      and approximately 150-250 nm in diameter, show significant enhancement of target
      specificity to tumor cells by additions of F3 and CGKRK THPs. We report herein
      the preparation and study of novel nanoscale silk-based ionic complexes
      containing pDNA able to home specifically to tumor cells. Particular focus was on
      how the THP, F3 (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK), and CGKRK, enhanced
      transfection specificity to tumor cells. Genetically engineered silk proteins
      containing both poly(L-lysine) domains to interact with pDNA and the THP to bind
      to specific tumor cells for target-specific pDNA delivery were prepared using
      Escherichia coli, followed by in vitro and in vivo transfection experiments into
      MDA-MB-435 melanoma cells and highly metastatic human breast tumor MDA-MB-231
      cells. Non-tumorigenic MCF-10A breast epithelial cells were used as a control
      cell line for in vitro tumor-specific delivery studies. These results demonstrate
      that combination of the bioengineered silk delivery systems and THP can serve as
      a versatile and useful new platform for nonviral gene delivery.

PMID- 21739967
TI  - An abridged transition state model to derive structure, dynamics, and energy
      components of DNA polymerase beta fidelity.
AB  - We show how a restricted reaction surface can be used to facilitate the
      calculation of biologically important contributions of active site geometries and
      dynamics to DNA polymerase fidelity. Our analysis, using human DNA polymerase
      beta (pol beta), is performed within the framework of an electrostatic linear
      free energy response (EFER) model. The structure, dynamics, and energetics of pol
      beta-DNA-dNTP interactions are computed between two points on the
      multidimensional reaction free energy surface. "Point 1" represents a ground
      state activation intermediate (GSA), which is obtained by deprotonating the
      terminal 3'OH group of the primer DNA strand. "Point 2" is the transition state
      (PTS) for the attack of the 3'O(-) (O(nuc)) on the P(alpha) atom of dNTP
      substrate, having the electron density of a dianionic phosphorane intermediate.
      Classical molecular dynamics simulations are used to compute the geometric and
      dynamic contributions to the formation of right and wrong O(nuc)-P chemical
      bonds. Matched dCTP.G and mismatched dATP.G base pairs are used to illustrate the
      analysis. Compared to the dCTP.G base pair, the dATP.G mismatch has fewer GSA
      configurations with short distances between O(nuc) and P(alpha) atoms and between
      the oxygen in the scissile P-O bond (O(lg)) and the nearest structural water. The
      thumb subdomain conformation of the GSA complex is more open for the mismatch,
      and the H-bonds in the mispair become more extended during the nucleophilic
      attack than in the correct pair. The electrostatic contributions of pol beta and
      DNA residues to catalysis of the right and wrong P-O(nuc) bond formation are 5.3
      and 3.1 kcal/mol, respectively, resulting in an 80-fold contribution to fidelity.
      The EFER calculations illustrate the considerable importance of Arg183 and an
      O(lg)-proximal water molecule to pol beta fidelity.

PMID- 21739968
TI  - Metal-ligand cooperation by aromatization-dearomatization: a new paradigm in bond
      activation and "green" catalysis.
AB  - In view of global concerns regarding the environment and sustainable energy
      resources, there is a strong need for the discovery of new, green catalytic
      reactions. For this purpose, fresh approaches to catalytic design are desirable.
      In recent years, complexes based on "cooperating" ligands have exhibited
      remarkable catalytic activity. These ligands cooperate with the metal center by
      undergoing reversible structural changes in the processes of substrate activation
      and product formation. We have discovered a new mode of metal-ligand cooperation,
      involving aromatization-dearomatization of ligands. Pincer-type ligands based on
      pyridine or acridine exhibit such cooperation, leading to unusual bond activation
      processes and to novel, environmentally benign catalysis. Bond activation takes
      place with no formal change in the metal oxidation state, and so far the
      activation of H-H, C-H (sp(2) and sp(3)), O-H, and N-H bonds has been
      demonstrated. Using this approach, we have demonstrated a unique water splitting
      process, which involves consecutive thermal liberation of H(2) and light-induced
      liberation of O(2), using no sacrificial reagents, promoted by a pyridine-based
      pincer ruthenium complex. An acridine pincer complex displays unique "long-range"
      metal-ligand cooperation in the activation of H(2) and in reaction with ammonia.
      In this Account, we begin by providing an overview of the metal-ligand
      cooperation based on aromatization-dearomatization processes. We then describe a
      range of novel catalytic reactions that we developed guided by these new modes of
      metal-ligand cooperation. These reactions include the following: (1) acceptorless
      dehydrogenation of secondary alcohols to ketones, (2) acceptorless
      dehydrogenative coupling of alcohols to esters, (3) acylation of secondary
      alcohols by esters with dihydrogen liberation, (4) direct coupling of alcohols
      and amines to form amides and polyamides with liberation of dihydrogen, (5)
      coupling of esters and amines to form amides with H(2) liberation, (6) selective
      synthesis of imines from alcohols and amines, (6) facile catalytic hydrogenolysis
      of esters to alcohols, (7) hydrogenolysis of amides to alcohols and amines, (8)
      hydrogenation of ketones to secondary alcohols under mild hydrogen pressures, (9)
      direct conversion of alcohols to acetals and dihydrogen, and (10) selective
      synthesis of primary amines directly from alcohols and ammonia. These reactions
      are efficient, proceed under neutral conditions, and produce no waste, the only
      byproduct being molecular hydrogen and/or water, providing a foundation for new,
      highly atom economical, green synthetic processes.

PMID- 21739970
TI  - Spin polarized metastable helium de-excitation processes on metal surfaces.
AB  - Spin polarized de-excitation of a metastable helium atom interacting with metal
      surfaces is treated within density functional theory. The method is based on a
      self-consistent calculation of the spin dependent electronic properties of the
      system, such as the surface density of states and the localized surface states,
      to compute the transition rate. On the high work function Ag(100) and Ag(111)
      surfaces, the helium 2s electron is delocalized in the metal and hence the
      transition rate is weakly spin dependent. The existence of a Shockley surface
      state in Ag(111) determines a neutralization rate that is about 59% larger than
      that from Ag(100). On a low work function metal, namely Na(100), the rate is of
      smaller magnitude than those on silver because the 2s triplet resonance is found
      to be more occupied. Consequently, emitted electrons can display a strong spin
      dependence also for a paramagnetic surface.

PMID- 21739971
TI  - General and modular synthesis of isomeric 5-substituted pyridin-2-yl and 6
      substituted pyridin-3-yl C-ribonucleosides bearing diverse alkyl, aryl, hetaryl,
      amino, carbamoyl, and hydroxy groups.
AB  - A general modular and practical methodology for preparation of diverse 5
      substituted pyridin-2-yl and 6-substituted pyridin-3-yl C-ribonucleosides was
      developed. Regioselective lithiation of 2,5-dibromopyridine proceeded at position
      5 or 2 depending on the solvent, and the resulting bromopyridyl lithium species
      underwent additions to TBS-protected ribonolactone and follow-up transformations
      to corresponding acetylated hemiketal intermediates 7 and 10 that were
      diastereoselectively reduced to give either 5-bromopyridin-2-yl or 6-bromopyridin
      3-yl silyl-protected C-ribonucleosides 8 or 11 in 68% and 77% overall yields as
      pure beta-anomers. These bromopyridyl C-nucleoside intermediates were then
      subjected to a series of palladium-catalyzed cross-coupling reactions,
      aminations, aminocarbonylations, and hydroxylations to give a series of protected
      1beta-(5-alkyl-, 5-aryl-, 5-amino-, 5-carbamoyl-, and 5-hydroxypyridin-2-yl)-C
      ribonucleosides 13a-i and beta-(6-alkyl-, 6-aryl-, 6-amino-, 6-carbamoyl-, and 6
      hydroxypyridin-3-yl)-C-ribonucleosides 15a-i. Deprotection of silylated
      nucleosides by Et(3)N.3HF, TBAF, or TFA gave a series of free C-nucleosides 14a-i
      and 16a-i.

PMID- 21739972
TI  - Synthesis of gamma-monofluorinated goniothalamin analogues via regio- and
      stereoselective ring-opening hydrofluorination of epoxide.
AB  - A stereoselective synthesis of the biologically interesting gamma-monofluorinated
      goniothalamin analogue 2a was described. The features of the synthesis included
      regioselective reduction of the unprotected hydroxypropynyl moiety of compound 10
      by Red-Al, asymmetric Sharpless epoxidation of allyl alcohol 11, and regio- and
      stereoselective ring-opening hydrofluorination of the hydroxypropynyl epoxide 14
      with Et(3)N.3HF in high ee and dr. The chiral hydroxypropynyl fluorohydrin 15 was
      used as a valuable building block for preparation of a range of gamma
      monofluorinated alpha,beta-unsaturated delta-lactones.

PMID- 21739973
TI  - Interatomic magnetizability: a QTAIM-based approach toward deciphering magnetic
      aromaticity.
AB  - Interatomic magnetizability provides insight into the extent of electronic
      current density between two adjacent atomic basins. By studying a number of well
      known aromatic, nonaromatic, and antiaromatic molecules, it is demonstrated that
      interatomic magnetizability (bond magnetizability) not only is able to verify the
      exact nature of aromaticity/antiaromaticity among different molecules, but also
      can distinguish the correct aromaticity order among sets of aromatic/antiaromatic
      molecules. The interatomic magnetizability is a direct measure of the current
      flux between two adjacent atomic basins and is the first QTAIM-derived index that
      evaluates aromaticity based on a response property, that is, magnetizability.
      Bond magnetizability is easy to compute, straightforward to interpret, and can be
      employed to evaluate the pure pi- or sigma-orbital contributions to magnetic
      aromaticity.

PMID- 21739974
TI  - 4-acetylantroquinonol B isolated from Antrodia cinnamomea arrests proliferation
      of human hepatocellular carcinoma HepG2 cell by affecting p53, p21 and p27
      levels.
AB  - The 4-acetylantroquinonol B isolated from the mycelium of Antrodia cinnamomea
      could inhibit proliferation of hepatocellular carcinoma cells HepG2 with IC(50)
      0.1 MUg/mL. When the HepG2 cells were treated with 4-acetylantroquinonol B for 72
      h, the proportion of cells in the G1 phase of the cell cycle increased and that
      in the S phase decreased significantly, and the proportion of G2/M phase cells
      were not obviously changed. In addition, the 4-acetylantroquinonol B treatment
      resulted in the decreases of CDK2 and CDK4, and an increase of p27 in a dose
      dependent manner. The protein levels of p53 and p21 proteins were also increased
      when the cells were treated with low dosage (0.1 MUg/mL) of 4-acetylantroquinonol
      B. Higher dosages, however, decreased the expression of p53 and p21 proteins.
      Assay of RT-PCR indicated that, corresponding to the increases of p53 and p21
      proteins at the dosage of 0.1 MUg/mL, the mRNAs of p53 and p21 showed 1.66- and
      1.61-fold upregulations, respectively. Corresponding to the decreases of CDK2 and
      CDK4 proteins, the mRNAs of CDK2 and CDK4 showed -1.02- and -1.13-fold
      downregulations, respectively. However, level of p27 mRNA showed -1.2-fold
      downregulation in spite of the increase in p27 protein. This observation, again,
      confirms the fact that the p27 gene rarely undergoes homozygous inactivation in
      cancer cells. Our finding suggested that the 4-acetylantroquinonol B inhibits
      proliferation of HepG2 cells via affecting p53, p21 and p27 proteins, and can be
      considered as a potential cancer drug.

PMID- 21739975
TI  - Oligophenylenaminones as scaffolds for alpha-helix mimicry.
AB  - The design and synthesis of small molecule alpha-helix mimetics has been a
      productive field over the past decade. These compounds have performed well in a
      variety of biological systems as functional disruptors of alpha-helix-mediated
      protein-protein interactions. In our studies we have continued to develop novel,
      more biologically compatible scaffolds, which are often easier to assemble and
      capable of mimicking longer and/or more diverse helices. To this end, we have
      constructed a new series of i, i+4, i+7 alpha-helix mimics based on the enaminone
      scaffold. These molecules represent a step forward in the pursuit of idealized
      monofacial alpha-helix mimetics.

PMID- 21739976
TI  - Meltable dextran esters as biocompatible and functional coating materials.
AB  - The conversion of dextran with in situ synthesized iminium chlorides of long
      chain carboxylic acids was used to obtain pure and defined melting dextran esters
      in an efficient one-pot synthesis. The melting point of these esters can be
      tailored by the degree of substitutions (DS), the molecular weight of the
      starting polymer, and the chain length of the ester moiety. The dextran esters
      give homogeneous and completely transparent melts, which form stable films on a
      broad variety of materials. Even complex geometries, such as implants, can be
      evenly coated by multiple melting steps. The films do not display any
      inhomogeneity and have a very low surface roughness. Therefore, no unspecific
      protein binding is observed. Moreover, the dextran esters are biocompatible as
      demonstrated for the interaction with three types of cells namely human brain
      microvascular endothelial cell, primary human fibroblasts, and mouse myoblast
      cells.

PMID- 21739977
TI  - Combined C-H functionalization/Cope rearrangement with vinyl ethers as a
      surrogate for the vinylogous Mukaiyama aldol reaction.
AB  - Vinyl ethers selectively undergo the combined C-H functionalization/Cope
      rearrangement reaction via an s-cis/boat transition state. With chiral dirhodium
      catalysts, products are generated in a highly diastereoselective and
      enantioselective fashion. This reaction can be considered as a surrogate to the
      traditional vinylogous Mukaiyama aldol reaction. Effective kinetic resolution has
      been achieved, leading to the recovery of a cyclic vinyl ether with axial
      chirality of high enantiomeric purity.

PMID- 21739978
TI  - Wild brown trout affected by historical mining in the Cevennes National Park,
      France.
AB  - In the protected area of the Cevennes National Park (Southern France), 114 wild
      brown trout (Salmo trutta fario) were captured at six locations affected to
      different extents by historical mining and metallurgy dating from the Iron Age to
      Modern Times. Cadmium and lead in trout livers and muscles reflect high sediment
      contamination, although an age-related effect was also detected for hepatic metal
      concentrations. Lead isotope signatures confirm exposure to drainage from mining
      and metallurgical waste. Developmental instability, assessed by fluctuating
      asymmetry, is significantly correlated with cadmium and lead concentrations in
      trout tissues, suggesting that local contamination may have affected fish
      development. Nowadays, the area is among the least industrialized in France.
      However, our results show that 60% of the specimens at one site exceed EU maximum
      allowed cadmium or lead concentration in foodstuffs. The mining heritage should
      not be neglected when establishing strategies for long-term environmental
      management.

PMID- 21739980
TI  - Synthesis of pyrazoles via electrophilic cyclization.
AB  - Electrophilic cyclizations of alpha,beta-alkynic hydrazones by molecular iodine
      were investigated for the synthesis of 4-iodopyrazoles. alpha,beta-Alkynic
      hydrazones were readily prepared by the reactions of hydrazines with propargyl
      aldehydes and ketones. When treated with molecular iodine in the presence of
      sodium bicarbonate, alpha,beta-alkynic hydrazones underwent electrophilic
      cyclization to afford 4-iodopyrazoles in good to high yields. Iodocyclization was
      general for a wide range of alpha,beta-alkynic hydrazones and tolerated the
      presence of aliphatic, aromatic, heteroaromatic, and ferrocenyl moieties with
      electron-withdrawing and electron-donating substituents.

PMID- 21739979
TI  - Monitoring processivity and length control of a carbohydrate polymerase.
AB  - Carbohydrate polymerases are abundant in nature. Although they play vital
      physiological roles, the molecular mechanisms that they use for the controlled
      assembly of polymers are largely unknown. One fundamental issue is whether an
      enzyme utilizes a processive or distributive mechanism for chain elongation. The
      shortage of mechanistic information on polysaccharide-generating
      glycosyltransferases became apparent when we sought to carry out investigations
      of GlfT2, a glycosyltransferase essential for cell wall biosynthesis in
      Mycobacterium tuberculosis. GlfT2 catalyzes the formation of the cell wall
      galactan, which is a linear polysaccharide consisting of 20-40 repeating d
      galactofuranose (Galf) residues. Recombinant GlfT2 can act on synthetic acceptors
      to produce polymers with lengths similar to those of endogenous galactan,
      indicating that GlfT2 has an intrinsic ability to control polymer length. To
      address whether GlfT2 utilizes a processive or distributive mechanism, we
      developed a mass spectrometry assay. Our approach, which relies on acceptors
      labeled with stable isotopes, provides direct evidence that GlfT2 is a processive
      polymerase that maintains contact with the glycan substrate through successive
      monomer additions. Given this finding, we probed further the catalytic mechanism
      of GlfT2 to address the basis of an observed kinetic lag phase. These studies
      suggest that GlfT2 possesses subsites for Galf residue binding and that
      substrates that can fill these subsites undergo efficient processive
      polymerization. The presence of these subsites and the kinetic lag phase are
      common features of processive enzymes. We anticipate that the strategies
      described herein can be applied to mechanistic studies of other carbohydrate
      polymerization reactions.

PMID- 21739981
TI  - Atropisomerism-induced facial selectivity in nitrile oxide cycloadditions with 5
      methylenehydantoins.
AB  - N-Aryl 5-methylenehydantoins underwent nitrile oxide cycloaddition with
      benzonitrile oxide to give 5-spiro isoxazoline adducts with complete
      regioselectivity. Atropisomerism around the N-aryl bond also led to facial
      selectivity in these cycloadditions.

PMID- 21739982
TI  - Construction of the tricyclic furanochroman skeleton of phomactin A via the
      Prins/Conia-ene cascade cyclization approach.
AB  - A substrate-controlled asymmetric Prins/Conia-ene cascade cyclization has been
      developed with In(OTf)(3) in CH(3)CN from 0 to 70  degrees C. These conditions
      afforded very good yields of the 1-oxadecalin product in one pot and effectively
      suppressed the racemization of the 1-oxadecalin product with almost no
      enantiomeric excess (ee) loss. This cascade cyclization has been successfully
      employed for the construction of the highly functionalized 1-oxadecalin unit of
      phomactin A with an acyclic beta-keto ester and an alkynal as the substrates via
      a one-pot operation (66% yield, single diastereomer). The 1-oxadecalin moiety has
      been readily converted to the tricyclic furanochroman skeleton of phomactin A via
      the epoxidation/dealkoxycarbonylation protocol under very mild conditions with
      52% yield in three steps.

PMID- 21739983
TI  - A Co4O4 "cubane" water oxidation catalyst inspired by photosynthesis.
AB  - Herein we describe the molecular Co(4)O(4) cubane complex
      Co(4)O(4)(OAc)(4)(py)(4) (1), which catalyzes efficient water oxidizing activity
      when powered by a standard photochemical oxidation source or electrochemical
      oxidation. The pH dependence of catalysis, the turnover frequency, and in situ
      monitoring of catalytic species have revealed the intrinsic capabilities of this
      core type. The catalytic activity of complex 1 and analogous Mn(4)O(4) cubane
      complexes is attributed to the cubical core topology, which is analogous to that
      of nature's water oxidation catalyst, a cubical CaMn(4)O(5) cluster.

PMID- 21739985
TI  - Synthesis of maradolipid.
AB  - The first synthesis of maradolipid, a unique dissymmetrically 6,6'-di-O-acylated
      trehalose glycolipid isolated from C. elegans, is accomplished in five steps
      starting from trehalose in 45% overall yield. The short synthesis relies on
      dissymmetrization of trehalose core via regioselective acylation of a
      2,3,4,2',3',4'-hexa-O-TMS trehalose 6,6'-diol derivative as a key step.

PMID- 21739986
TI  - Total synthesis of (-)-anamarine.
AB  - Total synthesis of polyhydroxy delta-pyranone natural product (-)-anamarine is
      accomplished from D-(-)-tartaric acid. The main feature of the synthesis is the
      utility of hitherto unexplored beta-keto phosphonate derived from tartaric acid
      amide and further elaboration involving stereoselective reduction.

PMID- 21739987
TI  - Notable effects of the metal salts on the formation and decay reactions of alpha
      tocopheroxyl radical in acetonitrile solution. The complex formation between
      alpha-tocopheroxyl and metal cations.
AB  - The measurement of the UV-vis absorption spectrum of alpha-tocopheroxyl (alpha
      Toc(*)) radical was performed by reacting aroxyl (ArO(*)) radical with alpha
      tocopherol (alpha-TocH) in acetonitrile solution including four kinds of alkali
      and alkaline earth metal salts (MX or MX(2)) (LiClO(4), LiI, NaClO(4), and
      Mg(ClO(4))(2)), using stopped-flow spectrophotometry. The maximum wavelength
      (lambda(max)) of the absorption spectrum of the alpha-Toc(*) at 425.0 nm
      increased with increasing concentration of metal salts (0-0.500 M) in
      acetonitrile, and it approached constant values, suggesting an [alpha-Toc(*)-M(+)
      (or M(2+))] complex formation. The stability constants (K) were determined to be
      9.2, 2.8, and 45 M(-1) for LiClO(4), NaClO(4), and Mg(ClO(4))(2), respectively.
      By reacting ArO(*) with alpha-TocH in acetonitrile, the absorption of ArO(*)
      disappeared rapidly, while that of alpha-Toc(*) appeared and then decreased
      gradually as a result of the bimolecular self-reaction of alpha-Toc(*) after
      passing through the maximum. The second-order rate constants (k(s)) obtained for
      the reaction of alpha-TocH with ArO(*) increased linearly with an increasing
      concentration of metal salts. The results indicate that the hydrogen transfer
      reaction of alpha-TocH proceeds via an electron transfer intermediate from alpha
      TocH to ArO(*) radicals followed by proton transfer. Both the coordination of
      metal cations to the one-electron reduced anions of ArO(*) (ArO:(-)) and the
      coordination of counteranions to the one-electron oxidized cations of alpha-TocH
      (alpha-TocH(*)(+)) may stabilize the intermediate, resulting in the acceleration
      of electron transfer. A remarkable effect of metal salts on the rate of
      bimolecular self-reaction (2k(d)) of the alpha-Toc(*) radical was also observed.
      The rate constant (2k(d)) decreased rapidly with increasing concentrations of the
      metal salts. The 2k(d) value decreased at the same concentration of the metal
      salts in the following order: no metal salt > NaClO(4) > LiClO(4) >
      Mg(ClO(4))(2). The complex formation between alpha-Toc(*) and metal cations may
      stabilize the energy level of the reactants (alpha-Toc(*) + alpha-Toc(*)),
      resulting in the decrease of the rate constant (2k(d)). The alkali and alkaline
      earth metal salts having a smaller ionic radius of cation and a larger charge of
      cation gave larger K and k(s) values and a smaller 2k(d) value.

PMID- 21739988
TI  - Direct generation of acyclic polypropionate stereopolyads via double diastereo-
      and enantioselective iridium-catalyzed crotylation of 1,3-diols: beyond stepwise
      carbonyl addition in polyketide construction.
AB  - Under the conditions of transfer hydrogenation employing the cyclometalated
      iridium catalyst (R)-I derived from [Ir(cod)Cl](2), allyl acetate, 4-cyano-3
      nitrobenzoic acid, and the chiral phosphine ligand (R)-SEGPHOS, alpha-methylallyl
      acetate engages 1,3-propanediol (1a) and 2-methyl-1,3-propanediol (1b) in double
      carbonyl crotylation from the alcohol oxidation level to deliver the C(2)
      symmetric and pseudo-C(2)-symmetric stereopolyads 2a and 3a, respectively, with
      exceptional control of anti-diastereoselectivity and enantioselectivity. Notably,
      the polypropionate stereopentad 3a is formed predominantly as 1 of 16 possible
      stereoisomers. Desymmetrization of 3a is readily achieved upon iodoetherification
      to form pyran 4. The direct generation of 3a enables a dramatically simplified
      approach to previously prepared polypropionate substructures, as demonstrated by
      the synthesis of C19-C27 of rifamycin S (eight steps, originally prepared in 26
      steps) and C19-C25 of scytophycin C (eight steps, originally prepared in 15
      steps). The present transfer hydrogenation protocol represents an alternative to
      chiral auxiliaries, chiral reagents, and premetalated nucleophiles in polyketide
      construction.

PMID- 21739989
TI  - Antibacterial activity of conjugated polyelectrolytes with variable chain
      lengths.
AB  - Cationic poly(phenylene ethynylene)- (PPE-) based conjugated polyelectrolytes
      (CPEs) with six different chain lengths ranging in degree of polymerization from
      ~7 to ~49 were synthesized from organic-soluble precursor polymers. The molecular
      weight of the precursor polymers was controlled by the amount of a monofunctional
      "end-capping" agent added to the polymerization reaction. Cationic CPEs were
      prepared by quaternization of amine groups to tetraalkylammonium groups. Their
      structure-property relationships were investigated by observing their
      photophysical properties and antibacterial activity. The polymers were found to
      exhibit a chain-length dependence in their photophysical properties. It has also
      been observed that the polymers exhibit effective antibacterial activity against
      both Gram-positive and Gram-negative bacteria under UV irradiation, whereas they
      show little antibacterial activity in the dark. An effect of chain length on the
      light-activated antibacterial activity was also found: The shortest polymer (n=7)
      exhibited the most effective antibacterial activity against both Gram-positive
      and Gram-negative bacteria.

PMID- 21739990
TI  - Target-specific gene silencing of layer-by-layer assembled gold
      cysteamine/siRNA/PEI/HA nanocomplex.
AB  - Target-specific intracellular delivery of small interfering RNA (siRNA) is
      regarded as one of the most important technologies for the development of siRNA
      therapeutics. In this work, a cysteamine modified gold nanoparticles
      (AuCM)/siRNA/polyethyleneimine (PEI)/hyaluronic acid (HA) complex was
      successfully developed using a layer-by-layer method for target-specific
      intracellular delivery of siRNA by HA receptor mediated endocytosis. Atomic force
      microscopic and zeta potential analyses confirmed the formation of a
      AuCM/siRNA/PEI/HA complex having a particle size of ca. 37.3 nm and a negative
      surface charge of ca. -12 mV. With a negligible cytotoxicity, AuCM/siRNA/PEI/HA
      complex showed an excellent target-specific gene silencing efficiency of ca. 70%
      in the presence of 50 vol % serum, which was statistically much higher than that
      of siRNA/Lipofectamine 2000 complex. In the competitive binding tests with free
      HA, dark-field bioimaging and inductively coupled plasma-atomic emission
      spectroscopy confirmed the target-specific intracellular delivery of
      AuCM/siRNA/PEI/HA complex to B16F1 cells with HA receptors. Moreover, the
      systemic delivery of AuCM/siRNA/PEI/HA complex using apolipoprotein B (ApoB)
      siRNA as a model drug resulted in a significantly reduced ApoB mRNA level in the
      liver tissue. Taken together, AuCM/siRNA/PEI/HA complex was thought to be
      developed as target-specific siRNA therapeutics for the systemic treatment of
      various liver diseases.

PMID- 21739992
TI  - Highly stereoselective titanium-mediated aldol reaction from (S)-4-benzyloxy-3
      methyl-2-butanone.
AB  - Substrate-controlled titanium-mediated aldol reactions from (S)-4-benzyloxy-3
      methyl-2-butanone provide satisfactory levels of 2,5-syn asymmetric induction if
      they are carried out in the presence of a second equivalent of TiCl(4). Such
      reactions give high yields and excellent diastereoselectivity with a wide array
      of achiral and chiral aldehydes without needing other sources of chirality. This
      procedure is thus of interest for the synthesis of natural products. Furthermore,
      spectroscopic studies and analyses of the reacting species have revealed a
      possible mechanism to account for the experimental results.

PMID- 21739993
TI  - Evaluation of cadmium phytoremediation potential in Chinese cabbage cultivars.
AB  - Selecting a phytoextraction plant with moderate to high Cd-accumulating ability
      and high biomass based on the plant's compatibility with mechanized cultivation
      techniques may yield more immediately practical results. In the present study,
      six Chinese cabbage cultivars were grown in three soils, ranging from 0.15 to
      2.25 mg Cd kg(-1) soil, to examine uptake and translocation of Cd in their
      tissues. The results indicated that the order of the shoot Cd concentration
      values in the cultivars was as follows: Beijingxiaoza 56 > Suancaiwang >
      Quansheng and Qiubo 60 > Xianfengkuaicai and Chunkang. Similar order was also
      found in the bioaccumulation factor (BAF), translocation factor (TF), and metal
      extraction ratio (MER). Several soil Cd fractions after Beijingxiaoza 56
      harvesting decreased most. Beijingxiaoza 56 is thus promising for phytoextraction
      of Cd from soils with low to moderate (<2.25 mg kg(-1)) Cd contamination.

PMID- 21739994
TI  - A more reactive trigonal-bipyramidal high-spin oxoiron(IV) complex with a cis
      labile site.
AB  - The trigonal-bipyramidal high-spin (S = 2) oxoiron(IV) complex
      [Fe(IV)(O)(TMG(2)dien)(CH(3)CN)](2+) (7) was synthesized and spectroscopically
      characterized. Substitution of the CH(3)CN ligand by anions, demonstrated here
      for X = N(3)(-) and Cl(-), yielded additional S = 2 oxoiron(IV) complexes of
      general formulation [Fe(IV)(O)(TMG(2)dien)(X)](+) (7-X). The reduced steric bulk
      of 7 relative to the published S = 2 complex [Fe(IV)(O)(TMG(3)tren)](2+) (2) was
      reflected by enhanced rates of intermolecular substrate oxidation.

PMID- 21739995
TI  - Hierarchical carbon nanowire microarchitectures made by plasma-assisted pyrolysis
      of photoresist.
AB  - We present a new approach for the fabrication and integration of vertically
      aligned forests of amorphous carbon nanowires (CNWs), using only standard
      lithography, oxygen plasma treatment, and thermal processing. The simplicity and
      scalability of this process, as well as the hierarchical organization of CNWs,
      provides a potential alternative to the use of carbon nanotubes and graphene for
      applications in microsystems and high surface area materials. The CNWs are highly
      branched at the nanoscale, and novel hierarchical microstructures with CNWs
      connected to a solid amorphous core are made by controlling the plasma treatment
      time. By multilayer processing we demonstrate deterministic joining of CNW
      micropillars into 3D sensing networks. Finally we show that these networks can be
      chemically functionalized and used for measurement of DNA binding with increased
      sensitivity.

PMID- 21739996
TI  - In vitro antimicrobial activity of aminoreductone against the pathogenic bacteria
      methicillin-resistant Staphylococcus aureus (MRSA).
AB  - In this study, antimicrobial activity of aminoreductone (AR), a product formed
      during the initial stage of the Maillard reaction, against methicillin-resistant
      Staphylococcus aureus (MRSA) was evaluated. The significant growth inhibition of
      all 51 MRSA isolates irrespective of drug susceptibility by AR was observed. The
      minimum inhibitory concentration (MIC) of AR ranged from 13 to 26 mM. The
      bactericidal activity of AR was evaluated by a killing assay with multiples of
      MIC, and it was recognized to depend on its dose. The combined effects of AR and
      antibiotics frequently used for the treatment of infections caused by Gram
      positive and Gram-negative bacteria, such as amikacin (AN), ciprofloxacin,
      imipenem and levofloxacin, were examined. As a result, AR did not interfere with
      these antibiotic activities against 12 MRSA isolates selected and showed the
      advanced effect of growth inhibition in combination with antibiotics. Moreover,
      the inhibitory effects of AR were similar to those of AN, an antibiotic with
      known adverse effects, some serious. These findings show that AR is a naturally
      formed antimicrobial agent present in thermally processed foods with potential
      health benefits in medical practice.

PMID- 21739998
TI  - Excited-state dynamics of trans,trans-1,3,5,7-octatetraene: estimation of decay
      rate constants of 1(1)B(u) ? 2(1)A(g) and 2(1)A(g) ? 1(1)A(g) internal
      conversions.
AB  - The general expressions we previously derived for calculating internal conversion
      rate constants between two adiabatic displaced-distorted-rotated potential energy
      surfaces, by including all vibratinal modes, are applied to estimate the decay
      rate constants of 1(1)B(u) ? 2(1)A(g) and 2(1)A(g) ? 1(1)A(g) internal
      conversions in trans,trans-1,3,5,7-octatetraene molecule. The minimal models with
      respect to the number and types of vibrational modes are determined for these
      processes. Our calculations show that in the low temperature limit the 1(1)B(u) ?
      2(1)A(g) internal conversion takes place on a 232-290 fs time scale in the
      condensed phase and 2 ps in the gas phase, whereas 2(1)A(g) ? 1(1)A(g) internal
      conversion takes place on a 2 MUs time scale under the isolated conditions.

PMID- 21739997
TI  - Glutathionylation at Cys-111 induces dissociation of wild type and FALS mutant
      SOD1 dimers.
AB  - Mutation of the ubiquitous cytosolic enzyme Cu/Zn superoxide dismutase (SOD1) is
      hypothesized to cause familial amyotrophic lateral sclerosis (FALS) through
      structural destabilization leading to misfolding and aggregation. Considering the
      late onset of symptoms as well as the phenotypic variability among patients with
      identical SOD1 mutations, it is clear that nongenetic factor(s) impact ALS
      etiology and disease progression. Here we examine the effect of Cys-111
      glutathionylation, a physiologically prevalent post-translational oxidative
      modification, on the stabilities of wild type SOD1 and two phenotypically diverse
      FALS mutants, A4V and I112T. Glutathionylation results in profound
      destabilization of SOD1(WT) dimers, increasing the equilibrium dissociation
      constant K(d) to ~10-20 MUM, comparable to that of the aggressive A4V mutant.
      SOD1(A4V) is further destabilized by glutathionylation, experiencing an ~30-fold
      increase in K(d). Dissociation kinetics of glutathionylated SOD1(WT) and
      SOD1(A4V) are unchanged, as measured by surface plasmon resonance, indicating
      that glutathionylation destabilizes these variants by decreasing association
      rate. In contrast, SOD1(I112T) has a modestly increased dissociation rate but no
      change in K(d) when glutathionylated. Using computational structural modeling, we
      show that the distinct effects of glutathionylation on different SOD1 variants
      correspond to changes in composition of the dimer interface. Our experimental and
      computational results show that Cys-111 glutathionylation induces structural
      rearrangements that modulate stability of both wild type and FALS mutant SOD1.
      The distinct sensitivities of SOD1 variants to glutathionylation, a modification
      that acts in part as a coping mechanism for oxidative stress, suggest a novel
      mode by which redox regulation and aggregation propensity interact in ALS.

PMID- 21739999
TI  - Physicochemical and flavor characteristics of flavoring agent from mungbean
      protein hydrolyzed by bromelain.
AB  - Enzymatic bromelain mungbean meal protein hydrolysate (eb-MPH) was produced from
      mungbean meal protein isolate (MPI). Enzymatic bromelain, with a known protease
      activity of 98,652 (unit/g), was used at concentrations of 0, 2, 6, 10, 14 and
      18% (w/w) and with hydrolysis times of 0.5, 3, 6, 12, and 24 h. The pH and
      temperature were controlled at 6.0 and 50  degrees C, respectively. It was found
      that the best treatment combination for eb-MPH production by response surface
      methodology (RSM) was 18% bromelain and a hydrolysis time of 3 h, resulting in
      the greatest degree of hydrolysis (% DH) and percent yield, with values of 61.04
      and 45.63%, respectively. Results also showed that the phenylalanine, tyrosine
      and leucine contents of the optimally produced eb-MPH were 20.88, 14.50 and
      10.93%, respectively. Twelve volatile compounds were identified using gas
      chromatography mass spectrometry in eb-MPH; benzaldehyde, 2-pentylfuran and
      furfural were the predominant odorants.

PMID- 21740000
TI  - Importance of sialic acid residues illuminated by live animal imaging using
      phosphorylcholine self-assembled monolayer-coated quantum dots.
AB  - Glycans are expected to be one of the potential signal molecules for controlling
      drug targeting/delivery or long-term circulation of biopharmaceuticals. However,
      the effect of the carbohydrates of artificially glycosylated derivatives on in
      vivo dynamic distribution profiles after intravenous injection of model animals
      remains unclear due to the lack of standardized methodology and a suitable
      platform. We report herein an efficient and versatile method for the preparation
      of multifunctional quantum dots (QDs) displaying common synthetic glycosides with
      excellent solubility and long-term stability in aqueous solution without loss of
      quantum yields. Combined use of an aminooxy-terminated thiol derivative, 11,11'
      dithio bis[undec-11-yl 12-(aminooxyacetyl)amino hexa(ethyleneglycol)], and a
      phosphorylcholine derivative, 11-mercaptoundecylphosphorylcholine, provided QDs
      with novel functions for the chemical ligation of ketone-functionalized compounds
      and the prevention of nonspecific protein adsorption concurrently. In vivo near
      infrared (NIR) fluorescence imaging of phosphorylcholine self-assembled monolayer
      (SAM)-coated QDs displaying various simple sugars (glyco-PC-QDs) after
      administration into the tail vein of the mouse revealed that distinct long-term
      delocalization over 2 h can be achieved in cases of QDs modified with alpha
      sialic acid residue (Neu5Ac-PC-QDs) and control PC-QDs, while QDs bearing other
      common sugars, such as alpha-glucose (Glc-PC-QDs), alpha-mannose (Man-PC-QDs),
      alpha-fucose (Fuc-PC-QDs), lactose (Lac-PC-QDs), beta-glucuronic acid (GlcA-PC
      QDs), N-acetyl-beta-D-glucosamine (GlcNAc-PC-QDs), and N-acetyl-beta-D
      galactosamine (GalNAc-PC-QDs) residues, accumulated rapidly (5-10 min) in the
      liver. Sequential enzymatic modifications of GlcNAc-PC-QDs gave Galbeta1,4GlcNAc
      PC-QDs (LacNAc-PC-QDs), Galbeta1,4(Fucalpha1,3)GlcNAc-PC-QDs (Le(x)-PC-QDs),
      Neu5Acalpha2,3Galbeta1,4GlcNAc-PC-QDs (sialyl LacNAc-PC-QDs), and
      Neu5Acalpha2,3Galbeta1,4(Fucalpha1,3)GlcNAc-PC-QDs (sialyl Le(x)-PC-QDs) in
      quantitative yield as monitored by direct matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry analyses. Live animal imaging
      uncovered for the first time that Le(x)-PC-QDs also distributed rapidly in the
      liver after intravenous injection and almost quenched over 1 h in similar
      profiles to those of LacNAc-PC-QDs and Lac-PC-QDs. On the other hand, sialyl
      LacNAc-PC-QDs and sialyl Le(x)-PC-QDs were still retained stably in the whole
      body after 2 h, while they showed significantly different in vivo dynamics in the
      tissue distribution, suggesting that structure/sequence of the neighboring sugar
      residues in the individual sialyl oligosaccharides might influence the final
      organ-specific distribution. The present results clearly visualize the evidence
      of an essential role of the terminal sialic acid residue(s) for achieving
      prolonged in vivo lifetime and biodistribution of various glyco-PC-QDs as a novel
      class of functional platforms for nanomaterial-based drug targeting/delivery. A
      standardized protocol using multifunctional PC-QDs should facilitate live animal
      imaging of ligand-displayed QDs using versatile NIR fluorescence photometry
      without influence of size-dependent accumulation/excretion pathway for
      nanoparticles (e.g., viruses) >10 nm in hydrodynamic diameter by the liver.

PMID- 21740001
TI  - High-precision measurement of variations in calcium isotope ratios in urine by
      multiple collector inductively coupled plasma mass spectrometry.
AB  - We describe a new chemical separation method to isolate Ca from other matrix
      elements in biological samples, developed with the long-term goal of making high
      precision measurement of natural stable Ca isotope variations a clinically
      applicable tool to assess bone mineral balance. A new two-column procedure
      utilizing HBr achieves the purity required to accurately and precisely measure
      two Ca isotope ratios ((44)Ca/(42)Ca and (44)Ca/(43)Ca) on a Neptune multiple
      collector inductively coupled plasma mass spectrometer (MC-ICPMS) in urine.
      Purification requirements for Sr, Ti, and K (Ca/Sr > 10 000; Ca/Ti > 10 000 000;
      and Ca/K > 10) were determined by addition of these elements to Ca standards of
      known isotopic composition. Accuracy was determined by (1) comparing Ca isotope
      results for samples and standards to published data obtained using thermal
      ionization mass spectrometry (TIMS), (2) adding a Ca standard of known isotopic
      composition to a urine sample purified of Ca, and (3) analyzing mixtures of urine
      samples and standards in varying proportions. The accuracy and precision of
      delta(44/42)Ca measurements of purified samples containing 25 MUg of Ca can be
      determined with typical errors less than +/-0.20/00 (2sigma).

PMID- 21740002
TI  - Harnessing tumor necrosis factor receptors to enhance antitumor activities of
      drugs.
AB  - Cancer is the second-leading cause of death in the U.S. behind heart disease and
      over stroke. The hallmarks of cancer comprise six biological capabilities
      acquired during the multistep development of human tumors. The inhibition of cell
      death pathways is one of these tumor characteristics which also include sustained
      proliferative signaling, evading growth suppressor signaling, replicative
      immortality, angiogenesis, and promotion of invasion and metastasis. Cell death
      is mediated through death receptor (DR) stimulation initiated by specific ligands
      that transmit signaling to the cell death machinery or through the participation
      of mitochondria. Cell death involving DR is mediated by the superfamily of tumor
      necrosis factor receptor (TNF-R) which includes TNF-R type I, CD95, DR3, TNF
      related apoptosis-inducing ligand (TRAIL) receptor-1 (TRAIL-R1) and -2 (TRAIL
      R2), DR6, ectodysplasin A (EDA) receptor (EDAR), and the nerve growth factor
      (NGF) receptor (NGFR). The expression of these receptors in healthy and tumor
      cells induces treatment side effects that limit the systemic administration of
      cell death-inducing therapies. The present review is focused on the different
      therapeutic strategies such as targeted antibodies or small molecules addressed
      to selective stimulated DR-mediated apoptosis or reduce cell proliferation in
      cancer cells.

PMID- 21740003
TI  - Sterol transfer between cyclodextrin and membranes: similar but not identical
      mechanism to NPC2-mediated cholesterol transfer.
AB  - Niemann--Pick C disease is an inherited disorder in which cholesterol and other
      lipids accumulate in the late endosomal/lysosomal compartment. Recently,
      cyclodextrins (CD) have been shown to reduce symptoms and extend lifespan in
      animal models of the disease. In the present studies we examined the mechanism of
      sterol transport by CD using in vitro model systems and fluorescence spectroscopy
      and NPC2-deficient fibroblasts. We demonstrate that cholesterol transport from
      the lysosomal cholesterol-binding protein NPC2 to CD occurs via aqueous
      diffusional transfer and is very slow; the rate-limiting step appears to be
      dissociation of cholesterol from NPC2, suggesting that specific interactions
      between NPC2 and CD do not occur. In contrast, the transfer rate of the
      fluorescent cholesterol analogue dehydroergosterol (DHE) from CD to phospholipid
      membranes is very rapid and is directly proportional to the acceptor membrane
      concentration, as is DHE transfer from membranes to CD. Moreover, CD dramatically
      increases the rate of sterol transfer between membranes, with rates that can
      approach those mediated by NPC2. The results suggest that sterol transfer from CD
      to membranes occurs by a collisional transfer mechanism involving direct
      interaction of CD with membranes, similar to that shown previously for NPC2. For
      CD, however, absolute rates are slower compared to NPC2 for a given
      concentration, and the lysosomal phospholipid lysobisphosphatidic acid (LBPA)
      does not stimulate rates of sterol transfer between membranes and CD. As expected
      from the apparent absence of interaction between CD and NPC2, the addition of CD
      to NPC2-deficient fibroblasts rapidly rescued the cholesterol accumulation
      phenotype. Thus, the recent observations of CD efficacy in mouse models of NPC
      disease are likely the result of CD enhancement of cholesterol transport between
      membranes, with rapid sterol transfer occurring during CD--membrane interactions.

PMID- 21740004
TI  - Comment on Climate change and mercury accumulation in Canadian High and Subarctic
      lakes.

PMID- 21740005
TI  - Increasing the role of economics in environmental research (or moving beyond the
      mindset that economics = accounting).

PMID- 21740007
TI  - Structure and lithium transport pathways in Li2FeSiO4 cathodes for lithium
      batteries.
AB  - The importance of exploring new low-cost and safe cathodes for large-scale
      lithium batteries has led to increasing interest in Li(2)FeSiO(4). The structure
      of Li(2)FeSiO(4) undergoes significant change on cycling, from the as-prepared
      gamma(s) form to an inverse beta(II) polymorph; therefore it is important to
      establish the structure of the cycled material. In gamma(s) half the LiO(4),
      FeO(4), and SiO(4) tetrahedra point in opposite directions in an ordered manner
      and exhibit extensive edge sharing. Transformation to the inverse beta(II)
      polymorph on cycling involves inversion of half the SiO(4), FeO(4), and LiO(4)
      tetrahedra, such that they all now point in the same direction, eliminating edge
      sharing between cation sites and flattening the oxygen layers. As a result of the
      structural changes, Li(+) transport paths and corresponding Li-Li separations in
      the cycled structure are quite different from the as-prepared material, as
      revealed here by computer modeling, and involve distinct zigzag paths between
      both Li sites and through intervening unoccupied octahedral sites that share
      faces with the LiO(4) tetrahedra.

PMID- 21740008
TI  - Vision 2020: more needed in materials reuse and recycling to avoid land
      contamination.

PMID- 21740009
TI  - Laboratory studies on the fate of perfluoroalkyl carboxylates and sulfonates
      during snowmelt.
AB  - Perfluoroalkyl acids (PFAAs) are anthropogenic chemicals that occur in snow from
      both remote and source regions. Experiments were conducted to determine how PFAAs
      are released from a melting snowpack. Different PFAAs eluted from the snowpack at
      different times, those with short chains eluting early, those with long chains
      eluting late. The concentrations in the meltwater of PFAAs with medium chain
      lengths of 6 to 9 perfluorinated carbon atoms first increased and then decreased
      during the melt period. Such a peak elution had not been previously observed for
      any other chemicals. The specific snow surface area (SSA) influenced this elution
      type, with peak concentrations occurring earlier in a snowpack with lower SSA.
      Model simulations suggested that the snow surface decrease during the melt alone
      was insufficient to explain the observations. It was ruled out that the calcium
      concentration affected PFAA sorption to the snow surface in a similar way as
      sorption to sediments. Adsorption coefficients of PFAAs to the snow surface were
      estimated by fitting the measured and modeled elution profiles.

PMID- 21740011
TI  - Direct observation and measurement of mobile charge carriers in a monolayer
      organic semiconductor on a dielectric substrate.
AB  - We report the electrical characterization of a single layer of an organic
      semiconductor grown on a dielectric surface. The dynamic response of the charge
      carriers in the monolayer film of pentacene was characterized through the
      electrostatic interactions between an electric force microscope (EFM) probe and
      pentacene islands of various sizes. These islands were formed in situ by
      segmenting a coalesced pentacene monolayer into separated regions. The size
      dependent dielectric responses of the pentacene islands suggest that mobile
      charges exist in the organic monolayer. Local capacitance spectroscopy revealed
      that the charge carriers in the p-type pentacene monolayer could be depleted at
      high bias voltages, enabling a further determination of the charge-carrier
      concentration in the organic semiconductor ultrathin film.

PMID- 21740010
TI  - Confocal Raman microscopy of pH-gradient-based 10 000-fold preconcentration of
      compounds within individual, optically trapped phospholipid vesicles.
AB  - A stable pH gradient established across the membrane of phospholipid vesicle can
      induce the accumulation of ionizable compounds from bulk solution into the
      vesicle interior. This pH-gradient vesicle loading process has previously been
      utilized to encapsulate drugs in pharmaceutical liposomal formulations. In the
      present work, this process is exploited to preconcentrate dilute analytes from
      free solution into phospholipid vesicles, which are then detected by optically
      trapping individual vesicles and measuring their contents using confocal Raman
      microscopy. The theory of accumulation, based on the acid-base ionization
      equilibria of the analyte, is developed to account for depletion of the source
      phase and the finite buffering capacity of the vesicle interior. The model
      predicts that, under appropriate conditions, enrichment factors of more than 4
      orders of magnitude can be realized. To test the concept, experiments were
      performed measuring the accumulation of benzyldimethylamine into 600-nm
      phospholipid vesicles. Manipulation of vesicles by optical trapping allows
      accumulation within an individual vesicle to be characterized while varying the
      external solution conditions. A more than 10 000-fold enrichment of the analyte
      concentration inside the vesicle relative to the source phase is reported. The
      results suggest that pH-gradient loading could be exploited as a powerful
      preconcentration scheme for trace analysis using either Raman microscopy or other
      microspectroscopy techniques.

PMID- 21740012
TI  - Assessment of enzymatic methods in the delta18O value determination of the L
      tyrosine p-hydroxy group for proof of illegal meat and bone meal feeding to
      cattle.
AB  - The delta(18)O value of the p-hydroxy group of L-tyrosine depends on the
      biosynthesis by plants or animals, respectively. In animal proteins it reflects
      the diet and is therefore an absolute indicator for illegal feeding with meat and
      bone meal. The aim of this investigation was to perform the positional (18)O
      determination on L-tyrosine via a one-step enzymatic degradation. Proteins from
      plants, herbivores, omnivores, and carnivores were characterized by their
      delta(13)C, delta(15)N, and delta(18)O values, the latter for normalizing the
      positional delta(18)O values. Their L-tyrosine was degraded by tyrosine phenol
      lyase to phenol, analyzed as (2,4,6)-tribromophenol. Degradation by tyrosine
      decarboxylase yielded tyramine. The delta(18)O values of both analytes
      corresponded to the trophic levels of their sources but were not identical,
      probably due to an isotope effect on the tyrosine phenol lyase reaction.
      Availability of the enzyme, easy control of the reaction, and isolation of the
      analyte are in favor of tyrosine decarboxylase degradation as a routine method.

PMID- 21740013
TI  - Na2CsBe6B5O15: an alkaline beryllium borate as a deep-UV nonlinear optical
      crystal.
AB  - A new deep-UV nonlinear optical crystal, Na(2)CsBe(6)B(5)O(15), has been grown
      through spontaneous crystallization with a molten flux based on Na(2)O-Cs(2)O
      B(2)O(3). Na(2)CsBe(6)B(5)O(15) contains two-dimensional alveolate beryllium
      borate layers [Be(2)BO(5)](infinity) that are bridged via planar [BO(3)] groups.
      UV-vis diffuse reflectance analysis on a powder sample of Na(2)CsBe(6)B(5)O(15)
      indicates that the short-wavelength absorption edge of Na(2)CsBe(6)B(5)O(15) is
      below 200 nm. Second-harmonic generation (SHG) on the powder sample was measured
      with a 1064 nm laser using the Kurtz and Perry technique, which showed that
      Na(2)CsBe(6)B(5)O(15) is a phase-matchable material, and its measured SHG
      coefficient is ~1.17 times as large as the d(36) coefficient of potassium
      dihydrogen phosphate. The relatively larger SHG coefficient of
      Na(2)CsBe(6)B(5)O(15) originates from its shorter distance between the adjacent
      layers bridged via the small [BO(3)] groups.

PMID- 21740014
TI  - Hybrid quantum mechanics/molecular mechanics-based molecular dynamics simulation
      of acid-catalyzed dehydration of polyols in liquid water.
AB  - We use the conversion of protonated glycerol to acrolein for a case study of the
      mechanism of acid-catalyzed dehydration of polyols in aqueous environments. We
      employ hybrid Quamtum Mechanics/Molecular Mechanics Molecular Dynamics (QM/MM MD)
      simulations with biased sampling and perform free energy calculations for the
      elementary steps of the reaction. We investigate the effects of solvent dynamics
      and in particular the role of quantum mechanical water in the dehydration
      mechanism. We present results supporting a mechanism that proceeds via water
      mediated proton transfers and thus through an enol intermediate. We find that the
      first dehydration may take place by two, low-energy pathways requiring,
      respectively, 20.9 and 18.8 kcal/mol of activation free energy. The second
      dehydration requires 19.9 kcal/mol of activation free energy while for the
      overall reaction we compute a free energy change of -8 kcal/mol.

PMID- 21740015
TI  - Model to couple anaerobic process kinetics with biological growth equilibrium
      thermodynamics.
AB  - Monod kinetics indicates a substrate concentration limit (S(min)) at biological
      growth equilibrium where growth is just balanced by decay. A relationship between
      S(min) and the Gibbs free energy available at growth equilibrium (DeltaG(E)) was
      introduced into the Monod model and applied directly to chemostat cultures.
      Results from four anaerobic mixed-culture chemostat studies yielded DeltaG(E) of 
      17.7 +/- 2.2 kJ/mol acetate converted to methane. DeltaG(E) for propionate
      syntrophs in propionate-fed cultures was -8.0 +/- 3.1 kJ/mol propionate, compared
      with that of -3.0 +/- 0.9 kJ/mol H(2) for the hydrogenotrophs present. With
      ethanol present, however, DeltaG(E) for the hydrogenotrophs became more
      favorable, -6.1 +/- 1.6 kJ/mol H(2), while DeltaG(E) for propionate became
      positive even though propionate was consumed, suggesting an alternative
      interspecies electron transport route. The results suggest that S(min), normally
      considered a function of an organism's intrinsic rate characteristics, is also a
      function of solution characteristics, and this is likely the case for the
      substrate affinity coefficient, K, as well. A comparison between DeltaG(E) and
      S(min) and reported threshold thermodynamic and concentration limits, leads to
      the conclusion that DeltaG(E) and S(min) represent lower and upper bounds,
      respectively, on such values. This study indicates that knowledge gained from
      pure-culture studies applies well to more complex natural anaerobic systems.

PMID- 21740019
TI  - Covalent reinforcement of hydrogen-bonded discs into stably folded helical
      structures.
AB  - The presence of covalent tethers significantly enhanced the stability of
      structures consisting of helically arranged benzenetricarboxamide units that
      otherwise undergo very weak hydrogen-bonding interaction. The resultant molecular
      structures were probed by computational study, which predicted folded
      conformations consisting of helically arranged discs. Experimental studies
      confirmed the H-bonding interaction between the disk units, the monomeric nature
      of the corresponding molecules in solution, and the helical conformations of such
      molecules.

PMID- 21740018
TI  - Accelerated ring-opening metathesis polymerization of a secondary amide of 1
      cyclobutene by hydrogen-bonding interaction.
AB  - A hydrogen-bond-assisted model is proposed for ring-opening metathesis
      polymerization (ROMP) of a secondary amide of 1-cyclobutene, resulting in the
      fastest reaction rate in a nonpolar solvent, toluene. This new model was
      supported by the investigation on how the solvent effect affected the NMR
      spectra, ROMP kinetic studies, and the copolymerization of monomers 1 and 2.

PMID- 21740017
TI  - Effect of polymer chain length on membrane perturbation activity of cationic
      phenylene ethynylene oligomers and polymers.
AB  - The interactions of poly(phenylene ethynylene)- (PPE-) based cationic conjugated
      polyelectrolytes (CPEs) and oligo(phenylene ethynylene)s (OPEs) with different
      model lipid membrane systems were investigated to gain insight into the
      relationship between molecular structure and membrane perturbation ability. The
      CPE and OPE compounds exhibit broad-spectrum antimicrobial activity, and cell
      walls and membranes are believed to be their main targets. To better understand
      how the size, in terms of the number of repeat units, of the CPEs and OPEs
      affects their membrane disruption activities, a series of PPE-based CPEs and OPEs
      were synthesized and studied. A number of photophysical techniques were used to
      investigate the interactions of CPEs and OPEs with model membranes, including
      unilamellar vesicles and lipid monolayers at the air/water interface. CPE- or OPE
      induced dye leakage from vesicles reveals that the CPEs and OPEs selectively
      perturb model bacterial membranes and that their membrane perturbation abilities
      are highly dependent on molecular size. Consistent with dye-leakage assay
      results, the CPEs and OPEs also exhibit chain-length-dependent ability to insert
      into 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) monolayers.
      Our results suggest that, for PPE-based CPE and OPE antimicrobials, chain length
      can be tuned to optimize their membrane perturbation ability.

PMID- 21740022
TI  - Room temperature water splitting at the surface of magnetite.
AB  - An array of surface science measurements has revealed novel water adsorption
      behavior at the Fe(3)O(4)(001) surface. Following room temperature exposure to
      water, a low coverage of hydrogen atoms is observed, with no associated water
      hydroxyl group. Mild annealing of the hydrogenated surface leads to desorption of
      water via abstraction of surface oxygen atoms, leading to a reduction of the
      surface. These results point to an irreversible splitting of the water molecule.
      The observed phenomena are discussed in the context of recent DFT calculations
      (Mulakaluri, N.; Pentcheva, R.; Scheffler, M. J. Phys. Chem. C 2010, 114, 11148),
      which show that the Jahn-Teller distorted surface isolates adsorbed H in a
      geometry that could kinetically hinder recombinative desorption. In contrast, the
      adsorption geometry facilitates interaction between water hydroxyl species, which
      are concluded to leave the surface following a reactive desorption process,
      possibly via the creation of O(2).

PMID- 21740020
TI  - A cycloisomerization/Friedel-Crafts alkylation strategy for the synthesis of
      pyrano[3,4-b]indoles.
AB  - The synthesis of pyrano[3,4-b]indoles is described. The reaction sequence
      involves Sonogashira coupling of dihydropyran propargyl ether scaffolds with
      iodoanilines to afford intermediate indoles. Lewis acid-catalyzed ionization of
      the dihydropyrans, followed by intramolecular C3 alkylation of the indole,
      provides the title compounds.

PMID- 21740023
TI  - Probing the transition from hydrophilic to hydrophobic solvation with atomic
      scale resolution.
AB  - Picosecond and femtosecond X-ray absorption spectroscopy is used to probe the
      changes of the solvent shell structure upon electron abstraction of aqueous
      iodide using an ultrashort laser pulse. The transient L(1,3) edge EXAFS at 50 ps
      time delay points to the formation of an expanded water cavity around the iodine
      atom, in good agreement with classical and quantum mechanical/molecular mechanics
      (QM/MM) molecular dynamics (MD) simulations. These also show that while the
      hydrogen atoms pointed toward iodide, they predominantly point toward the bulk
      solvent in the case of iodine, suggesting a hydrophobic behavior. This is further
      confirmed by quantum chemical (QC) calculations of I(-)/I(0)(H(2)O)(n=1-4)
      clusters. The L(1) edge sub-picosecond spectra point to the existence of a
      transient species that is not present at 50 ps. The QC calculations and the QM/MM
      MD simulations identify this transient species as an I(0)(OH(2)) complex inside
      the cavity. The simulations show that upon electron abstraction most of the water
      molecules move away from iodine, while one comes closer to form the complex that
      lives for 3-4 ps. This time is governed by the reorganization of the main
      solvation shell, basically the time it takes for the water molecules to reform an
      H-bond network. Only then is the interaction with the solvation shell strong
      enough to pull the water molecule of the complex toward the bulk solvent.
      Overall, much of the behavior at early times is determined by the reorientational
      dynamics of water molecules and the formation of a complete network of hydrogen
      bonded molecules in the first solvation shell.

PMID- 21740024
TI  - General and selective iron-catalyzed transfer hydrogenation of nitroarenes
      without base.
AB  - The first well-defined iron-based catalyst system for the reduction of
      nitroarenes to anilines has been developed applying formic acid as reducing
      agent. A broad range of substrates including other reducible functional groups
      were converted to the corresponding anilines in good to excellent yields at mild
      conditions. Notably, the process constitutes a rare example of base-free transfer
      hydrogenations.

PMID- 21740025
TI  - Identification of trichotoxin, a novel chlorinated compound associated with the
      bloom forming Cyanobacterium, Trichodesmium thiebautii.
AB  - Trichodesmium is a suspected toxin-producing nonheterocystous cyanobacteria
      ubiquitous in tropical, subtropical, and temperate seas. The genus is known for
      its ability to fix nitrogen and form massive blooms. In oligotrophic seas, it can
      dominate the biomass and be a major component of oceanic primary production and
      global nitrogen cycling. Numerous reports suggest Trichodesmium-derived toxins
      are a cause of death of fish, crabs, and bivalves. Laboratory studies have
      demonstrated neurotoxic effects in T. thiebautii cell extracts and field reports
      suggest respiratory distress and contact dermatitis of humans at collection
      sites. However, Trichodesmium toxins have not been identified and characterized.
      Here, we report the extraction of a lipophilic toxin from field-collected T.
      thiebautii using a purification method of several chromatographic techniques,
      nuclear magnetic resonance (NMR), mass spectroscopy (MS), and Fourier transformed
      infrared spectroscopy (FT-IR). Trichotoxin has a molecular formula of
      C(20)H(27)ClO and a mass of 318 m/z and possesses cytotoxic activity against
      GH(4)C(1) rat pituitary and Neuro-2a mouse neuroblastoma cells. A detection
      method using liquid chromatography/mass spectrometry (LC/MS) was developed. This
      compound is the first reported cytotoxic natural product isolated and fully
      characterized from a Trichodesmium species.

PMID- 21740026
TI  - Epitaxially guided assembly of collagen layers on mica surfaces.
AB  - Ordered assembly of collagen molecules on flat substrates has potential for
      various applications and serves as a model system for studying the assembly
      process. While previous studies demonstrated self-assembly of collagen on
      muscovite mica into highly ordered layers, the mechanism by which different
      conditions affect the resulting morphology remains to be elucidated. Using atomic
      force microscopy, we follow the assembly of collagen on muscovite mica at a
      concentration lower than the critical fibrillogenesis concentration in bulk.
      Initially, individual collagen molecules adsorb to mica and subsequently nucleate
      into fibrils possessing the 67 nm D-periodic bands. Emergence of fibrils aligned
      in parallel despite large interfibril distances agrees with an alignment
      mechanism guided by the underlying mica. The epitaxial growth was further
      confirmed by the formation of novel triangular networks of collagen fibrils on
      phlogopite mica, whose surface lattice is known to have a hexagonal symmetry,
      whereas the more widely used muscovite does not. Comparing collagen assembly on
      the two types of mica at different potassium concentrations revealed that
      potassium binds to the negatively charged mica surface and neutralizes it,
      thereby reducing the binding affinity of collagen and enhancing surface
      diffusion. These results suggest that collagen assembly on mica follows the
      surface adsorption, diffusion, nucleation, and growth pathway, where the growth
      direction is determined at the nucleation step. Comparison with other molecules
      that assemble similarly on mica supports generality of the proposed assembly
      mechanism, the knowledge of which will be useful for controlling the resulting
      surface morphologies.

PMID- 21740027
TI  - Making unilamellar liposomes using focused ultrasound.
AB  - Several techniques are available for making large unilamellar vesicles (LUV) with
      an average diameter of approximately 100 nm, widely employed as model
      biomembranes as well as vehicles for drug delivery. Here we describe the use of
      adaptive focused ultrasound (AFU) for the preparation of LUV from multilamellar
      vesicles (MLV) and studied the effects of ultrasound intensity and number of
      cycles per burst (CPB) on the average size of vesicles produced. CPB determines
      the duration of the intermittent pressure wavetrains emitted by the transducer,
      and the corresponding relaxation periods. Preliminary experiments indicated that
      CPB controls the size of vesicles assembling after the disruption of MLV by
      ultrasound and optimum values for obtaining LUV could be iterated. The sizes and
      lamellarity of LUV were assessed by dynamic light scattering (DLS), cryogenic
      transmission electron microscopy (cryo-TEM), and fluorescence quenching. AFU
      provides a simple and easy to use approach for making liposomes with several
      advantages: it is minimally invasive and involves no loss of material. Precisely
      controlled wavelengths are employed with a significant reduction in the presence
      of hot spots, which could destroy some biological materials of interest.

PMID- 21740028
TI  - Dependence of single-molecule conductance on molecule junction symmetry.
AB  - The symmetry of a molecule junction has been shown to play a significant role in
      determining the conductance of the molecule, but the details of how conductance
      changes with symmetry have heretofore been unknown. Herein, we investigate a
      naphthalenedithiol single-molecule system in which sulfur atoms from the molecule
      are anchored to two facing gold electrodes. In the studied system, the highest
      single-molecule conductance, for a molecule junction of 1,4-symmetry, is 110
      times larger than the lowest single-molecule conductance, for a molecule junction
      of 2,7-symmetry. We demonstrate clearly that the measured dependence of molecule
      junction symmetry for single-molecule junctions agrees with theoretical
      predictions.

PMID- 21740021
TI  - Proteome of human perilymph.
AB  - Current diagnostic tools limit a clinician's ability to discriminate between many
      possible causes of sensorineural hearing loss. This constraint leads to the
      frequent diagnosis of the idiopathic condition, leaving patients without a clear
      prognosis and only general treatment options. As a first step toward developing
      new diagnostic tools and improving patient care, we report the first use of
      liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to map the proteome of
      human perilymph. Using LC-MS/MS, we analyzed four samples, two collected from
      patients with vestibular schwannoma (VS) and two from patients undergoing
      cochlear implantation (CI). For each cohort, one sample contained pooled
      specimens collected from five patients and the second contained a specimen
      obtained from a single patient. Of the 271 proteins identified with high
      confidence among the samples, 71 proteins were common in every sample and used to
      conservatively define the proteome of human perilymph. Comparison to human
      cerebrospinal fluid and blood plasma, as well as murine perilymph, showed
      significant similarity in protein content across fluids; however, a quantitative
      comparison was not possible. Fifteen candidate biomarkers of VS were identified
      by comparing VS and CI samples. This list will be used in future investigations
      targeted at discriminating between VS tumors associated with good versus poor
      hearing.

PMID- 21740029
TI  - Testosterone-mineralizing culture enriched from swine manure: characterization of
      degradation pathways and microbial community composition.
AB  - Environmental releases and fate of steroid sex hormones from livestock and
      wastewater treatment plants are of increasing regulatory concern. Despite the
      detection of these hormones in manures, biosolids, and the environment, little
      attention has been paid to characterization of fecal bacteria capable of hormone
      degradation. The enrichments of (swine) manure-borne bacteria capable of aerobic
      testosterone degradation were prepared and the testosterone mineralization
      pathway was elucidated. Six DNA sequences of bacteria from the Proteobacteria
      phylum distributed among the genera Acinetobacter, Brevundimonas, Comamonas,
      Sphingomonas, Stenotrophomonas, and Rhodobacter were identified in a testosterone
      degrading enriched culture with testosterone as the sole carbon source. Three
      degradation products of testosterone were identified as androstenedione,
      androstadienedione, and dehydrotestosterone using commercially available
      reference standards, liquid chromatography-UV diode array detection, and liquid
      chromatography-time-of-flight mass spectrometry (LC-TOF/MS). Three additional
      degradation products of testosterone were tentatively identified as 9alpha
      hydroxytestosterone, 9alpha-hydroxyandrostadienedione or 3-hydroxy-9,10
      secoandrosta-1,3,5(10)-triene-9,17-dione, and 9alpha-hydroxydehydrotestosterone
      or 9alpha-hydroxyandrostenedione using LC-TOF/MS. When (14)C-testosterone was
      introduced to the enriched culture, 49-68% of the added (14)C-testosterone was
      mineralized to (14)CO(2) within 8 days of incubation. The mineralization of (14)C
      testosterone followed pseudo-first-order reaction kinetics in the enriched
      culture with half-lives (t(1/2)) of 10-143 h. This work suggests that
      Proteobacteria play an important environmental role in degradation of steroid sex
      hormones and that androgens have the potential to be mineralized during aerobic
      manure treatment or after land application to agricultural fields by manure-borne
      bacteria.

PMID- 21740030
TI  - Identifying new persistent and bioaccumulative organics among chemicals in
      commerce II: pharmaceuticals.
AB  - The goal of this study was to identify commercial pharmaceuticals that might be
      persistent and bioaccumulative (P&B) and that were not being considered in
      current wastewater and aquatic environmental measurement programs. We developed a
      database of 3193 pharmaceuticals from two U.S. Food and Drug Administration (FDA)
      databases and some lists of top ranked or selling drugs. Of the 3193
      pharmaceuticals, 275 pharmaceuticals have been found in the environment and 399
      pharmaceuticals were, based upon production volumes, designated as high
      production volume (HPV) pharmaceuticals. All pharmaceuticals that had reported
      chemical structures were evaluated for potential bioaccumulation (B) or
      persistence (P) using quantitative structure property relationships (QSPR) or
      scientific judgment. Of the 275 drugs detected in the environment, 92 were rated
      as potentially bioaccumulative, 121 were rated as potentially persistent, and 99
      were HPV pharmaceuticals. After removing the 275 pharmaceuticals previously
      detected in the environment, 58 HPV compounds were identified that were both P&B
      and 48 were identified as P only. Of the non-HPV compounds, 364 pharmaceuticals
      were identified that were P&B. This study has yielded some interesting and
      probable P&B pharmaceuticals that should be considered for further study.

PMID- 21740031
TI  - Synthetic hosts for molecular recognition of ureas.
AB  - Four hosts (7-10) containing 2,6-bisamidopyridine- and 2,5-bisamidopyrrole
      bearing pyridyl or 1,8-naphthyridyl groups have been prepared and their
      structures studied by a combination of multinuclear NMR spectroscopy and X-ray
      crystallography. Their behavior in molecular recognition of urea derivatives,
      including (+)-biotin methyl ester, has been approached by molecular modeling
      (Monte Carlo conformational search, AMBER force field). The minimum energy values
      for the complexes are correlated with the experimental binding energies
      determined by means of (1)H NMR titrations.

PMID- 21740034
TI  - Role of eDNA on the adhesion forces between Streptococcus mutans and substratum
      surfaces: influence of ionic strength and substratum hydrophobicity.
AB  - The aim of this study was to investigate the role of extracellular DNA (eDNA) on
      the adhesion strength of Streptococcus mutans LT11 on substrata with different
      hydrophobicities at high and low ionic strengths. AFM adhesion forces to a
      hydrophilic and hydrophobic substratum increased with increasing surface-delay
      times and ionic strength and were stronger on a hydrophobic than on a hydrophilic
      substratum. The presence of eDNA on the streptococcal cell surface enhanced its
      adhesion force to a hydrophobic substratum significantly more than to a
      hydrophilic substratum, especially after bond maturation. Bond maturation on a
      hydrophilic substratum was accompanied by an increasing number of minor adhesion
      peaks, indicating the involvement of acid-base interactions, whereas on the
      hydrophobic substratum surface the number of minor adhesion peaks remained low.
      More minor adhesion peaks developed on the hydrophilic substratum at low ionic
      strength than at high ionic strength. The final rupture distance in retraction
      force-distance curves was independent of ionic strength on a hydrophilic
      substratum and increased with increasing surface delay time. On the hydrophobic
      surface, the final rupture distance did not increase with surface delay time but
      was significantly smaller at low than at high ionic strength. Final rupture
      distances were different in presence and absence of eDNA, and the lower values of
      this difference coincided with the decrease in hydrodynamic radius of the
      streptococci upon increasing ionic strength, measured using dynamic light
      scattering. AFM also yielded higher values for the ionic strength induced
      difference in final rupture distance because in AFM rupture is forced, while in
      dynamic light scattering differences in radius are only induced by ionic strength
      differences.

PMID- 21740032
TI  - Room-temperature Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to
      maleimides and enones in the presence of CF3-substituted MeOBIPHEP analogues.
AB  - A Rh-based catalytic system implying electron-poor MeOBIPHEP analogues has been
      developed for the 1,4-addition of boronic acids to maleimides and enones under
      mild conditions at room temperature and led to succinimide derivatives and
      arylated cyclic ketones in good to excellent yields and ee. We uncovered the
      crucial role of the electronic and steric properties of diphosphine ligand and
      observed a strong boronic acid/ligand dependency in the case of maleimide
      derivatives and substrate/ligand matching in the case of cyclic enones.

PMID- 21740033
TI  - Application of small organic molecules reveals cooperative TGFbeta and BMP
      regulation of mesothelial cell behaviors.
AB  - Epicardial development is a process during which epithelial sheet movement,
      single cell migration, and differentiation are coordinated to generate coronary
      arteries. Signaling cascades regulate the concurrent and complex nature of these
      three events. Through simple and highly reproducible assays, we identified small
      organic molecules that impact signaling pathways regulating these epicardial
      behaviors. Subsequent biochemical analyses confirmed the specificity of these
      reagents and revealed novel targets for the widely used dorsomorphin (DM) and LDN
      193189 molecules. Using these newly characterized reagents, we show the broad
      regulation of epicardial cell differentiation, sheet movement, and single cell
      migration by Transforming Growth Factor beta (TGFbeta). With the DM analogue
      DMH1, a highly specific Bone Morphogenetic Protein (BMP) inhibitor, we
      demonstrate the cooperative yet exclusive role for BMP signaling in regulation of
      sheet migration. The action of DMH1 reveals that small organic molecules (SOM)
      can intervene on a single epicardial behavior while leaving other concurrent
      behaviors intact. All SOM data were confirmed by reciprocal experiments using
      growth factor addition and/or application of established non-SOM inhibitors.
      These compounds can be applied to cell lines or native proepicardial tissue.
      Taken together, these data establish the efficacy of chemical intervention for
      analysis of epicardial behaviors and provide novel reagents for analysis of
      epicardial development and repair.

PMID- 21740035
TI  - Accumulation and depuration of polychlorinated biphenyls from field-collected
      sediment in three freshwater organisms.
AB  - As laboratory-based bioaccumulation methods are standardized and expanded to
      include other test species, kinetic studies assessing the major classes of
      contaminants with these species are needed to adequately select the standard
      duration for bioaccumulation tests. In the present study we measured the uptake
      (28-d exposure) of polychlorinated biphenyls (PCBs; total and selected congeners)
      from field-contaminated sediment in the oligochaete Lumbriculus variegatus,
      mayfly nymph Hexagenia spp., and fathead minnow Pimephales promelas. Depuration
      (25 d) of PCBs was measured in organisms that had been transferred to clean
      sediment after the 28-d exposure. Uptake and elimination of PCBs was rapid in L.
      variegatus and Hexagenia spp. Tissue residues reached steady-state concentrations
      within 28 d; elimination rates and biota-sediment accumulation factors (BSAFs) of
      the PCB congeners were not correlated with K(OW). Uptake and elimination rates of
      PCBs were slower in P. promelas, and it is not clear whether steady-state was
      reached in fish tissues. Elimination rates of the PCB congeners significantly
      decreased with increasing K(OW) in fish. The appropriateness of a 28-d exposure
      for measuring steady-state concentrations in tissue of the invertebrates was
      confirmed, but further study is required for fish.

PMID- 21740036
TI  - Identification of c-type heme-containing peptides using nonactivated immobilized
      metal affinity chromatography resin enrichment and higher-energy collisional
      dissociation.
AB  - The c-type cytochromes play essential roles in many biological activities of both
      prokaryotic and eukaryotic cells, including electron transfer, enzyme catalysis,
      and induction of apoptosis. We report a novel enrichment strategy for identifying
      c-type heme-containing peptides that uses nonactivated IMAC resin. The strategy
      demonstrated at least 7-fold enrichment for heme-containing peptides digested
      from a cytochrome c protein standard, and quantitative linear performance was
      also assessed for heme-containing peptide enrichment. Heme-containing peptides
      extracted from the periplasmic fraction of Shewanella oneidensis MR-1 were
      further identified using higher-energy collisional dissociation tandem mass
      spectrometry. The results demonstrated the applicability of this enrichment
      strategy to identify c-type heme-containing peptides from a highly complex
      biological sample and, at the same time, confirmed the periplasmic localization
      of heme-containing proteins during suboxic respiration activities of S.
      oneidensis MR-1.

PMID- 21740037
TI  - Use of a coumarin-labeled hexa-arginine peptide as a fluorescent hydroxyl radical
      probe in a nanoparticulate plasmid DNA condensate.
AB  - Coumarin derivatives have found application as probes for the hydroxyl radical
      because one of the products of the reaction between them is a highly fluorescent
      umbelliferone. We have examined the interaction in aqueous solution between a
      cationic coumarin-labeled hexa-arginine peptide ligand and plasmid DNA, and
      compared after gamma irradiation the yields of products derived from both of
      them. At low ionic strengths, the ligand binds very tightly to the plasmid.
      Compared with the structurally similar 4-methylumbelliferone (phenolic pK(a) =
      7.8), the fluorescent product derived from gamma irradiation of the coumarin
      labeled cationic peptide is significantly more acidic (pK(a) = 6.1), making it a
      very convenient probe for solutions of pH in the physiological range. The yield
      of this product is generally in excellent agreement over a wide range of
      conditions with that of the single strand break product produced by the reaction
      of the hydroxyl radical with the plasmid. Thus coumarin-labeled peptide ligands
      offer promise as hydroxyl radical probes for locations in close proximity to DNA.

PMID- 21740039
TI  - Molecular dynamics simulation of water influence on local structure of
      nanoconfined polyamide-6,6.
AB  - Our recently developed molecular dynamics simulation method for simulating fluids
      confined in nanometric pores [Eslami et al. J. Chem. Phys.2008, 129, 194702] is
      employed to simulate nanoconfined polyamide-6,6+water in contact with graphene
      monolayers. In this work, a number of dry and wet polymer samples, containing 3
      and 6 wt % water at 350 K, confined in pores of different sizes as well as the
      bulk polymer samples are simulated. It is shown that both water and polymer
      molecules form organized layers beside the surfaces. The effect of
      nanoconfinement on the hydrogen bonding in the polymer+water system is studied in
      detail. It is shown that addition of water to the polymer replaces a fraction of
      looser amide-amide hydrogen bonds with amide-water ones. The distribution of
      hydrogen bond lengths shows that both the polymer and water form shorter length
      hydrogen bonds in the confined region compared to the bulk system. The number of
      hydrogen bonds between polymer and water molecules is shown to depend on the pore
      size and on the water content. In small pores, water molecules are forced by the
      surfaces into the polymer layers and form strong hydrogen bonds with the amide
      groups, a process that increases the water solubility of the polymer in small
      pores. Increasing the water content in larger pores increases the number of
      hydrogen bonds between water molecules and causes the formation of big clusters
      in the central region of the pore. In simulations of to 50 ns, it is shown that
      such big clusters grow with of time, and hence, phase separate out from the
      mixture.

PMID- 21740038
TI  - Solid-phase extraction and quantitative measurement of omega and omega-1
      metabolites of JWH-018 and JWH-073 in human urine.
AB  - The aminoalkylindole agonists JWH-018 and JWH-073 are contained in "K2/SPICE"
      products sold as "legal marijuana". Previous human metabolic studies have
      identified (omega)-hydroxyl and (omega)-carboxyl metabolites as biomarkers that
      are indicative of product use. However, other primary metabolites exhibiting
      similar chromatographic properties and mass spectra are also excreted in human
      urine. Analytical standards were used in this study to identify new primary
      metabolites as (omega-1)-hydroxyl derivatives of JWH-018 and JWH-073. The liquid
      chromatography tandem mass spectrometry (LC-MS/MS) procedure, coupled with an
      automated solid-phase extraction procedure incorporating deuterium-labeled
      internal standards, provides rapid resolution of the (omega)- and (omega-1)
      metabolites with adequate sensitivity, precision, and accuracy for trace analysis
      in human urine. Results from four urine specimens collected after individuals
      reportedly self-administered either JWH-018 or a mixture of JWH-018 and JWH-073
      showed the following: (1) all tested metabolites were excreted in high
      concentrations, (2) (omega)- and (omega-1)-hydroxyl metabolites were exclusively
      excreted as glucuronic acid conjugates, and (3) ~5%-80% of the (omega)-carboxyl
      metabolites was excreted as glucuronic acid conjugates. This is the first report
      to identify and quantify (omega-1)-hydroxyl metabolites of JWH-018 and JWH-073
      and the first to incorporate automated extraction procedures using deuterium
      labeled internal standards. Full clinical validation awaits further testing.

PMID- 21740040
TI  - Variation in energy available to populations of subsurface anaerobes in response
      to geological carbon storage.
AB  - Microorganisms can strongly influence the chemical and physical properties of the
      subsurface. Changes in microbial activity caused by geological CO(2) storage,
      therefore, have the potential to influence the capacity, injectivity, and
      integrity of CO(2) storage reservoirs and ultimately the environmental impact of
      CO(2) injection. This analysis uses free energy calculations to examine variation
      in energy available to Fe(III) and SO(4)(2-) reducers and methanogens because of
      changes in the bulk composition of brine and shallow groundwater following
      subsurface CO(2) injection. Calculations were performed using data from two field
      experiments, the Frio Formation experiment and an experiment at the Zero Emission
      Research and Technology test site. Energy available for Fe(III) reduction
      increased significantly during CO(2) injection in both experiments, largely
      because of a decrease in pH from near-neutral levels to just below 6. Energy
      available to SO(4)(2-) reducers and methanogens varied little. These changes can
      lead to a greater rate of microbial Fe(III) reduction following subsurface CO(2)
      injection in reservoirs where Fe(III) oxides or oxyhydroxides are available and
      the rate of Fe(III) reduction is limited by energy available prior to injection.

PMID- 21740041
TI  - Zinc oxide nanowire rigid platforms on elastomeric substrates.
AB  - Zinc oxide nanostructured thin films are transparent semiconducting ceramics
      increasingly used in a wide range of integrated devices. This paper outlines a
      simple strategy to integrate arrays of zinc oxide nanostructured thin films on
      elastomeric substrates using templated patterning. The arrays are robust to large
      uniaxial strains (up to 20% strain), do not fracture, and maintain electrical
      functionality. The integration of brittle nanostructured semiconducting materials
      on elastomeric substrates opens promising routes for the manufacture of
      deformable and stretchable electronics.

PMID- 21740045
TI  - Topography of the casein micelle surface by surface plasmon resonance (SPR) using
      a selection of specific monoclonal antibodies.
AB  - Several theoretical models of the casein micelle structure have been proposed in
      the past, but the exact organization of the four individual caseins (alpha(s1),
      alpha(s2), beta, and kappa) within this supramolecular structure remains unknown.
      The present study aims at determining the topography of the casein micelle
      surface by following the interaction between 44 monoclonal antibodies specific
      for different epitopes of alpha(s1)-, alpha(s2)-, beta-, and kappa-casein and the
      casein micelle in real time and no labeling using a surface plasmon resonance
      (SPR)-based biosensor. Although the four individual caseins were found to be
      accessible for antibody binding, data confirmed that the C-terminal extremity of
      kappa-casein was highly accessible and located at the periphery of the structure.
      When casein micelles were submitted to proteolysis, the C-terminal extremity of
      kappa-casein was rapidly hydrolyzed. Disintegration of the micellar structure
      resulted in an increased access for antibodies to hydrophobic areas of alpha(s1)-
      and alpha(s2)-casein.

PMID- 21740043
TI  - A multianalytical approach for determining the geographical origin of ginseng
      using strontium isotopes, multielements, and 1H NMR analysis.
AB  - Asian ginseng (Panax ginseng C.A. Meyer) is widely used as an Oriental medicine
      in the East Asian regions, particularly Korea and China. In the study, the
      strontium isotope ratios ((87)Sr/(86)Sr), multielements, and metabolite profiles
      of 35 ginseng samples collected from Korea and China were examined in an attempt
      to develop a method to distinguish the origin of ginsengs from the two countries.
      A multivariate statistical approach was performed to analyze the multielements
      and the (1)H nuclear magnetic resonance (NMR) data. Results of a t-test for Mg,
      Fe, Al, and Sc showed significant variation between Korean and Chinese ginsengs,
      indicating potential tracers for discriminating them. Discriminating between the
      ginsengs from the two countries was generally successful when both the
      (87)Sr/(86)Sr ratios and rare earth element (REE) contents were used together.
      Moreover, principal component analysis (PCA) derived from the (1)H NMR data
      revealed a significant separation between the ginsengs originating from the two
      countries. The major metabolites responsible for differentiation were sugars such
      as glucose, xylose, and sucrose. The results suggest that this multiplatform
      approach offers a comprehensive method to distinguish the origin of ginsengs.

PMID- 21740044
TI  - Occurrence of odorant polyfunctional thiols in the Super Alpha Tomahawk hop
      cultivar. Comparison with the thiol-rich Nelson Sauvin bitter variety.
AB  - Tomahawk hop (Humulus lupulus) is a recently developed Super Alpha cultivar (14
      18% alpha-acids w/w), already widely used by brewers to impart bitterness and a
      citrus-like aroma to beer. By comparison with two bitter varieties (Nelson Sauvin
      and Nugget) and two aromatic ones (Cascade and Saaz), the Tomahawk cultivar
      showed a very particular terpenoid profile, rich in both alpha- and beta
      selinenes (>600 mg/kg IST equiv in total), methyl geranate (>40 mg/kg IST equiv),
      and geraniol (>200 mg/kg). Tomahawk also proved to contain a wide variety of
      odorant polyfunctional thiols. The major beta-sulfanyl acetate, 3-sulfanyl-2
      ethylpropyl acetate, newly identified here, was found at similar levels in the
      famous Sauvignon-like Nelson Sauvin and Tomahawk varieties (15-44 MUg/kg IST
      equiv). On the other hand, lower levels of total beta-sulfanyl alcohols were
      measured in Tomahawk, although 3-sulfanylhexan-1-ol was found at a similar level
      and the 3-sulfanyl-4-methylpentan-1-ol previously claimed to be specific to the
      Nelson Sauvin variety was also evidenced in the Super Alpha cultivar (9-13 MUg/kg
      IST equiv). As revealed by boiling and fermentation, Tomahawk hop also contains
      very interesting bound polyfunctional thiols that should be investigated for
      better use by brewers.

PMID- 21740046
TI  - Thermoresponsive polymer brush on monolithic-silica-rod for the high-speed
      separation of bioactive compounds.
AB  - Poly(N-isopropylacrylamide), one of the most utilized thermoresponsive polymers,
      brush-grafted monolithic-silica columns were prepared through surface-initiated
      atom transfer radical polymerization (ATRP) for effective thermoresponsive
      chromatography matrices. ATRP initiator was grafted on monolithic silica-rod
      surfaces by flowing a toluene solution containing ATRP initiator into monolithic
      silica-rod columns. N-Isopropylacrylamide (IPAAm) monomer and
      CuCl/CuCl(2)/Me(6)TREN, an ATRP catalytic system, were dissolved in 2-propanol,
      and the reaction solution was pumped into the preprepared initiator-modified
      columns at 25  degrees C for 16 h. The constructed PIPAAm-brush structure on the
      monolithic silica-rod surface was confirmed by XPS, elemental analysis, SEM
      observation, and GPC measurement of grafted PIPAAm. The prepared monolithic
      silica-rod columns were also characterized by chromatographic analysis. PIPAAm
      brush-modified monolithic silica-rod columns were able to separate hydrophobic
      steroids with a short analysis time (10 min), compared to PIPAAm-brush-modified
      silica-beads-packed columns, because of the horizontally limited diffusion path
      length of monolithic supporting materials. Additionally, diluted PIPAAm-brush
      monolithic silica-rod column gave a further shorting analysis time (5 min). These
      results indicated (1) surface-initiated ATRP constructed PIPAAm-brush structures
      on monolithic silica-rod surfaces and (2) PIPAAm-brush grafted monolithic silica
      rod column prepared by ATRP was a promising tool for analyzing hydrophobic
      bioactive compounds with a short analysis time.

PMID- 21740042
TI  - Targeted vault nanoparticles engineered with an endosomolytic peptide deliver
      biomolecules to the cytoplasm.
AB  - Vault nanoparticles were engineered to enhance their escape from the endosomal
      compartment by fusing a membrane lytic peptide derived from adenovirus protein VI
      (pVI) to the N-terminus of the major vault protein to form pVI-vaults. We
      demonstrate that these pVI-vaults disrupt the endosomal membrane using three
      different experimental protocols including (1) enhancement of DNA transfection,
      (2) co-delivery of a cytosolic ribotoxin, and (3) direct visualization by
      fluorescence. Furthermore, direct targeting of vaults to specific cell surface
      epidermal growth factor receptors led to enhanced cellular uptake and efficient
      delivery of vaults to the cytoplasm. This process was monitored with fluorescent
      vaults, and morphological changes in the endosomal compartment were observed. By
      combining targeting and endosomal escape into a single recombinant vault, high
      levels of transfection efficiency were achieved using low numbers of vault
      particles. These results demonstrate that engineered vaults are effective,
      efficient, and nontoxic nanoparticles for targeted delivery of biomaterials to
      the cell cytoplasm.

PMID- 21740048
TI  - Deployment of a carbon isotope ratiometer for the monitoring of CO2 sequestration
      leakage.
AB  - In an effort to monitor leakage from underground CO(2) storage, a field
      deployable analyzer capable of rapidly measuring the CO(2) mixing ratio and
      delta(13)C values (+/-0.05 ppm(v) +/- 0.20/00, 60 s) was deployed to distinguish
      between biogenic and fossil CO(2) sources. The analyzer was interfaced with a
      multiport inlet unit to allow autonomous sampling from multiple locations. The
      instrument and inlet interface were deployed at the Zero Emissions Research and
      Technology (ZERT) site (Bozeman, Montana, July 14-22, 2009) during a controlled,
      subsurface release of CO(2) depleted in (13)C. A biogenic diurnal cycle was
      observed far from the release, and the associated Keeling plot suggested a CO(2)
      source (delta(13)C = -27.0 +/- 0.50/00) consistent with local C(3) vegetation.
      Inlets near the leak showed large CO(2) mixing ratios (388/>40 000 ppm(v)) whose
      predominant source was the release CO(2) (inferred delta(13)C = -58.2 +/-
      0.70/00). Measurements 3 m from the source showed diurnal CO(2) cycles (382-2400
      ppm(v)) influenced by leaked CO(2), possibly due to diel air mixing. Finally, the
      data from all of the sampling inlets was combined to spatially localize the leak
      position.

PMID- 21740047
TI  - Assembly of optical-scale dumbbells into dense photonic crystals.
AB  - We describe the self-assembly of nonspherical particles into crystals with novel
      structure and optical properties combining a partial photonic band gap with
      birefringence that can be modulated by an external field or quenched by solvent
      evaporation. Specifically, we study symmetric optical-scale polymer dumbbells
      with an aspect ratio of 1.58. Hard particles with this geometry have been
      predicted to crystallize in equilibrium at high concentrations. However, unlike
      spherical particles, which readily crystallize in the bulk, previous experiments
      have shown that these dumbbells crystallize only under strong confinement. Here,
      we demonstrate the use of an external electric field to align and assemble the
      dumbbells to make a birefringent suspension with structural color. When the
      electric field is turned off, the dumbbells rapidly lose their orientational
      order and the color and birefringence quickly go away. In this way, dumbbells
      combine the structural color of photonic crystals with the field addressability
      of liquid crystals. In addition, we find that if the solvent is removed in the
      presence of an electric field, the particles self-assemble into a novel, dense
      crystalline packing hundreds of particles thick. Analysis of the crystal
      structure indicates that the dumbbells have a packing fraction of 0.7862, higher
      than the densest known packings of spheres and ellipsoids. We perform numerical
      experiments to more generally demonstrate the importance of controlling the
      orientation of anisotropic particles during a concentration quench to achieve
      long-range order.

PMID- 21740049
TI  - Oligosaccharides as modulators of rheology in complex mucous systems.
AB  - Mucus rheology is integral to physiological function with the exact secretion
      rheology resulting from the macromolecular components, both mucin and nonmucin,
      and the interactions between these macromolecules. Here we present data
      demonstrating that low-molecular-weight guluronic acid oligomers extracted from
      alginate are able to disrupt intermolecular interactions in both purified and
      native mucous systems, resulting in rheological changes that are compatible with
      a lower cross-link density and thus reduced resistance to deformation.
      Additionally, these changes are associated with altered physiological function,
      raising the possibility of the use of such oligomers in biomedical applications.

PMID- 21740050
TI  - Preparation of monodisperse silicon nanocrystals using density gradient
      ultracentrifugation.
AB  - We report the preparation of monodisperse silicon nanocrystals (ncSi) by size
      separation of polydisperse alkyl-capped ncSi using organic density gradient
      ultracentrifugation. The ncSi were synthesized by thermal processing of
      trichlorosilane-derived sol-gel glasses followed by HF etching and surface
      passivation with alkyl chains and were subsequently fractionated by size using a
      self-generating density gradient of 40 wt % 2,4,6-tribromotoluene in
      chlorobenzene. The isolated monodisperse fractions were characterized by
      photoluminescence spectroscopy and high-angle annular dark-field scanning
      transmission electron microscopy and determined to have polydispersity index
      values between 1.04 and 1.06. The ability to isolate monodisperse ncSi will allow
      for the quantification of the size-dependent structural, optical, electrical, and
      biological properties of silicon, which will undoubtedly prove useful for
      tailoring property-specific optoelectronic and biomedical devices.

PMID- 21740051
TI  - Polyelectrolyte brushes grafted from cellulose nanocrystals using Cu-mediated
      surface-initiated controlled radical polymerization.
AB  - Herein we report the synthesis of cellulose nanocrystals (CNCs) grafted with
      poly(acrylic acid) (PAA) chains of different lengths using Cu-mediated surface
      initiated-controlled radical polymerization (SI-CRP). First, poly(tert
      butylacrylate) (PtBA) brushes were synthesized; then, subsequent acid hydrolysis
      was used to furnish PAA brushes tethered onto the CNC surfaces. The CNCs were
      chemically modified to create initiator moieties on the CNC surfaces using
      chemical vapor deposition (CVD) and continued in solvent phase in DMF. A density
      of initiator groups of 4.6 bromine ester groups/nm(2) on the CNC surface was
      reached, suggesting a dense functionalization and a promising starting point for
      the controlled/living radical polymerization. The SI-CRP of tert-butylacrylate
      proceeded in a well-controlled manner with the aid of added sacrificial
      initiator, yielding polymer brushes with polydispersity values typically well
      below 1.12. We calculated the polymer brush grafting density to almost 0.3
      chains/nm(2), corresponding to high grafting densities and dense polymer brush
      formation on the nanocrystals. Successful rapid acid hydrolysis to remove the
      tert-butyl groups yielded pH-responsive PAA-polyelectrolyte brushes bound to the
      CNC surface. Individually dispersed rod-like nanoparticles with brushes of PtBA
      or PAA were clearly visualized by AFM and TEM imaging.

PMID- 21740052
TI  - Gender-related differences in stereoselective degradation of flutriafol in
      rabbits.
AB  - The stereoselective pharmacokinetics of flutriafol were investigated in male and
      female adult Japanese white rabbits. Following intravenous administration of rac
      flutriafol to rabbits at 5 mg/kg (bd wt), the concentrations of the enantiomers
      in plasma were determined by a HLPC-UV method using a CDMPC-CSP chiral column. R
      Flutriafol exhibited a shorter distribution half-life but a longer elimination
      half-life than the S-isomer. In female rabbits, the distribution half-lives of R-
      and S-flutriafol were found to be 0.09 and 0.18 h, respectively, significantly
      shorter than those in male rabbits, but the volume of distribution and
      elimination half-life for flutriafol enantiomers in both sexes of rabbit showed
      no significant differences. Female rabbits had a higher clearance for both
      flutriafol enantiomers. The protein binding value was high for both isomers, with
      enantioselectivity, but no gender difference. It was an important factor in
      modulating the disposition of flutriafol. Flutriafol concentrations in kidney,
      liver, fat, and lung were higher than in other tissues at 10 h after
      administration, and the concentrations of R-flutriafol were higher in all tissues
      than those of its antipode. However, gender difference in flutriafol residues in
      tissues was not observed. It is concluded that the stereoselectivity of
      flutriafol on distribution and elimination in rabbits mainly depends upon gender.

PMID- 21740055
TI  - Evolution of order during vacuum-assisted self-assembly of graphene oxide paper
      and associated polymer nanocomposites.
AB  - Three mechanisms are proposed for the assembly of ordered, layered structures of
      graphene oxide, formed via the vacuum-assisted self-assembly of a dispersion of
      the two-dimensional nanosheets. These possible mechanisms for ordering at the
      filter-solution interface range from regular brick-and-mortar-like growth to
      complete disordered aggregation and compression. Through a series of experiments
      (thermal gravimetric analysis, UV-vis spectroscopy, and X-ray diffraction) a semi
      ordered accumulation mechanism is identified as being dominant during paper
      fabrication. Additionally, a higher length-scale ordered structure (lamellae) is
      identified through the examination of water-swelled samples, indicating that
      further refinements are required to capture the complete formation mechanism.
      Identification of this mechanism and the resulting higher-order structure it
      produces provide insight into possibilities for creation of ordered graphene
      oxide-polymer nanocomposites, as well as the postfabrication modification of
      single-component graphene oxide papers.

PMID- 21740057
TI  - The influence of the stereochemistry of alanine residue on the solid state
      conformation and crystal packing of opioid peptides containing D-Ala or L-Ala in
      message domain--XRD and NMR study.
AB  - In this work, an X-ray diffraction (XRD) and solid state NMR study of two
      tetrapeptides with different stereochemistry of alanine residue is presented
      using Tyr-(D-Ala)-Phe-Gly (1), an N-terminal sequence of opioid peptide
      dermorphin, and its biologically inactive analog Tyr-(L-Ala)-Phe-Gly (2). Single
      crystal XRD proved that 1 crystallized under different conditions from
      exclusively one structure: a monoclinic crystal with P2(1) space group. In
      contrast, 2 very easily formed at least three crystallographic modifications, 2a
      (monoclinic P2(1)), 2b (orthorhombic P2(1)2(1)2) and 2c (tetragonal P4(1)2(1)2).
      Solid-state NMR spectroscopy was employed to investigate the structure and
      molecular dynamics of 1, 2a, and 2b. By employing different NMR experiments
      (dipolar dephasing and PILGRIM) and an analysis of the (13)C principal elements
      of the chemical shift tensor (CST), it was proven that the main skeleton of
      tetrapeptides is rigid, whereas significant differences in the molecular motion
      of the aromatic residues were observed. Comparing current data with those of
      previous studies (J. Phys. Chem. B2004, 108, 4535-4545 and Cryst. Growth Des.
      2009, 9, 4050-4059), it can be assumed that an important preorganization
      mechanism anticipating the formation of peptide crystals containing D-Ala in
      sequence is the intramolecular CH-pi interaction, which occurs for the amino acid
      with D stereochemistry. This effect may be responsible for the formation of only
      one crystallographic form of D-Ala peptides.

PMID- 21740054
TI  - Experimental and theoretical study on the intermolecular complex formation
      between trehalose and benzene compounds in aqueous solution.
AB  - The uniqueness of trehalose as a stress protectant may exist in its potential
      amphiphilic character capable of interacting with both hydrophilic and
      hydrophobic partners in aqueous solution. To address this issue, we here
      investigated the interaction between trehalose and aromatic compounds. NMR
      measurements, including (1)H-(1)H NOESY spectra, provide direct evidence for the
      formation of stable intermolecular complexes of trehalose with benzene (or p
      cresol) in aqueous solution. In addition, corresponding theoretical evidence is
      provided by calculating the potential mean force as a function of the distance
      between trehalose and benzene. In the energy minimum structure, the benzene
      molecule is located only around the hydrophobic side of trehalose where the first
      hydration shell is not formed. Therefore, it can be concluded that benzene binds
      to trehalose in a fashion in which dehydration penalty is minimized. Finally, we
      discuss the possible biological roles of the trehalose-benzene interaction
      discovered here.

PMID- 21740053
TI  - The CUMULUS coarse graining method: transferable potentials for water and
      solutes.
AB  - Molecular dynamics (MD) simulations are an important tool for studying various
      interesting phenomena in nature at the molecular level. To allow molecular
      simulation methods to be applied to larger systems and for longer time scales,
      coarse grained (CG) models have been developed in which groups of atoms are
      represented by a single coarse grained particle. In so-called multiscale CG
      models, an atomistic simulation is coarse grained and subsequently used to derive
      a CG force field. Existing multiscale methods represent either (parts of)
      molecules as a single CG particle, or groups of molecules of fluctuating size as
      a single CG particle. Here, a novel method is introduced to coarse grain an
      atomistic simulation, the CUMULUS coarse graining method. In this method, CG
      particles have a unique, fixed composition. This important feature of our coarse
      graining method, which is not available in the current methods, provides a
      systematic method to include CG solute particles in solutions of salts in water.
      Combined with the iterative Boltzmann inversion procedure, our coarse graining
      method is employed to derive CG force fields for systems containing pure water,
      sodium chloride solutions, and water-octanol mixtures. It is found that the
      obtained force fields accurately reproduce the structural information from the
      atomistic simulations, as measured by the radial distribution functions.
      Furthermore, we conclude that the obtained CG force fields are transferable to
      systems of different composition for the systems studied here.

PMID- 21740060
TI  - Use of model peptide reactions for the characterization of kinetically controlled
      ligation.
AB  - Since the introduction of kinetically controlled ligation (KCL), a chemoselective
      reaction between a peptide-(alpha)thioarylester and a Cys-peptide
      (alpha)thioalkylester, KCL has been utilized for the total chemical synthesis of
      large proteins (i.e., lysozyme and HIV-protease) by providing fully convergent
      synthetic routes. Although KCL has the potential to become an important chemistry
      for protein synthesis, the principle of KCL is not fully characterized. In
      particular, prior work on KCL has focused on the reactivity difference of the two
      different -(alpha)thioester forms-alkyl vs aryl. Another equally important
      feature of KCL, Xaa-Cys ligation sites, has not been investigated. The work
      reported here describes combinatorial KCL reactions using model peptides to
      dissect the interplay of the Xaa(1), Xaa(2), -(alpha)thioarylester, and 
      (alpha)thioalkylester. Results from these studies provide fundamental insights
      into the KCL reaction, and will lead to the optimal synthetic route for the
      routine chemical synthesis of large target protein molecules.

PMID- 21740061
TI  - Solubilization of native integral membrane proteins in aqueous buffer by
      noncovalent chelation with monomethoxy poly(ethylene glycol) (mPEG) polymers.
AB  - Highly hydrophobic integral membrane proteins (IMPs)are typically purified in
      excess detergent media, often resulting in rapid inactivation and denaturation of
      the protein. One promising approach to solve this problem is to couple
      hydrophilic polymers, such as monomethoxypolyethylene glycol (mPEG) to IMPs under
      mild conditions in place of detergents. However, the broad application of this
      approach is hampered by poor reaction efficiencies, low tolerance of detergent
      stabilized membrane proteins to reaction conditions, and a lack of proper site
      specific reversible approaches. Here, we have developed a straightforward,
      efficient, and mild approach to site-specific noncovalent binding of long-chain
      polymers to recombinant IMPs. This method uses the hexa-histidine tag (His-Tag)
      often used for purification of recombinant proteins as an attachment site for
      mPEGs. Solubility studies performed using five different IMPs confirmed that all
      tested mPEG-bound IMPs were completely soluble and stable in detergent free
      aqueous buffer compared to their precipitated native proteins under the identical
      circumstances. Activity assays and circular dichroism (CD) spectroscopy confirmed
      the structural integrity of modified IMPs.

PMID- 21740058
TI  - Targeted, activatable, in vivo fluorescence imaging of prostate-specific membrane
      antigen (PSMA) positive tumors using the quenched humanized J591 antibody
      indocyanine green (ICG) conjugate.
AB  - In patients with prostate cancer, a positive surgical margin is associated with
      an increased risk of cancer recurrence and poorer outcome, yet margin status
      cannot be determined during the surgery. An in vivo optical imaging probe that
      could identify the tumor margins during surgery could result in improved
      outcomes. The design of such a probe focuses on a highly specific targeting
      moiety and a near-infrared (NIR) fluorophore that is activated only when bound to
      the tumor. In this study, we successfully synthesized an activatable monoclonal
      antibody-fluorophore conjugate consisting of a humanized anti-Prostate-Specific
      Membrane Antigen (PSMA) antibody (J591) linked to an indocyanine green (ICG)
      derivative. Prior to binding to PSMA and cellular internalization, the conjugate
      yielded little light; however, after binding an 18-fold activation was observed
      permitting the specific detection of PSMA+ tumors up to 10 days after injection
      of a low dose (0.25 mg/kg) of the reagent. This agent demonstrates promise as a
      method to image the extent of prostate cancer in vivo and could assist with real
      time resection of extracapsular extension of tumor and positive lymph nodes.

PMID- 21740064
TI  - Multilayered poly(vinylidene fluoride) composite membranes with improved
      interfacial compatibility: correlating pervaporation performance with free volume
      properties.
AB  - A spin-coating process integrated with an ozone-induced graft polymerization
      technique was applied in this study. The purpose was to improve the poor
      interfacial compatibility between a selective layer of poly(2-hydroxyethyl
      methacrylate) (PHEMA) and the surface of a poly(vinylidene fluoride) (PVDF)
      substrate. The composite membranes thus fabricated were tested for their
      pervaporation performance in dehydrating an ethyl acetate/water mixture.
      Furthermore, the composite membranes were characterized by field emission
      scanning electron microscopy (FE-SEM) for morphological change observation and by
      Fourier transform infrared spectroscopy equipped with attenuated total
      reflectance (ATR-FTIR) for surface chemical composition analysis. Effects of
      grafting density and spin-coating speed on pervaporation performance were
      examined. The composite membrane pervaporation performance was elucidated by
      means of free volume and depth profile data obtained with the use of a variable
      monoenergy slow positron beam (VMSPB). Results indicated that a smaller free
      volume was correlated with a higher pervaporation performance of a composite
      membrane consisting of a selective layer of spin-coated PHEMA on a PHEMA-grafted
      PVDF substrate (S-PHEMA/PHEMA-g-PVDF). The composite membrane depth profile
      illustrated that an S-PHEMA layer spin-coated at a higher revolutions per minute
      (rpm) was thinner and denser than that at a lower rpm.

PMID- 21740067
TI  - Proteomic analysis of skin defensive factors of tree frog Hyla simplex.
AB  - Tree frogs produce a variety of skin defensive chemicals against many biotic and
      abiotic risk factors for their everyday survival. By proteomics or peptidomics
      and coupling transcriptome analysis with pharmacological testings, 27 peptides or
      proteins belonging to 9 families, which act mainly as defensive functions, were
      identified and characterized from skin secretions of the tree frog, Hyla simplex.
      They are: (1) a novel family of peptides with EGF- and VEGF-releasing activities;
      (2) a novel family of analgesic peptides; (3) a family of neurotoxins acting on
      sodium channel; (4) a snake venom-like presynaptically active neurotoxin; (5) a
      snake venom-like neurotoxin targeting cyclic nucleotide-gated ion channels; (6) a
      tachykinin-like peptide, which is the first report from tree frogs; (7) two
      antimicrobial peptides; (8) a alpha-1-antitrypsin-like serpin; and (9) a wasp
      venom-like toxin with serine protease inhibitors activity. Families of 1, 2, 4,
      5, and 8 proteins or peptides are first reported in amphibians. The chemical
      array in the tree frog skin shares some similarities with snake venoms. Most of
      these components in this tree frog help defend against predators, heal wounds, or
      attenuate suffering.

PMID- 21740065
TI  - Stereoselective palladium-catalyzed alpha-arylation of 3-aryl-1-indanones: an
      asymmetric synthesis of (+)-pauciflorol F.
AB  - Highly stereoselective, palladium-catalyzed alpha-arylation reactions of 3-aryl-1
      indanones with aryl bromides are described. The use of sodium tert-butoxide as a
      base in this process is required to elevate the efficiencies and
      stereoselectivities of these reactions. The new methodology was successfully
      applied to a highly efficient route for the asymmetric synthesis of (+)
      pauciflorol F.

PMID- 21740062
TI  - Ionic-liquid induced changes in cellulose structure associated with enhanced
      biomass hydrolysis.
AB  - The effects of varying ionic liquid pretreatment parameters on various sources of
      lignocellulosic biomass have been studied using X-ray powder diffraction, X-ray
      fiber diffraction, and compositional analysis. Comparative enzymatic hydrolysis
      and sugar analysis were used to relate the observed changes in cellulose
      structure to biomass digestibility. In this study, the factor most clearly
      associated with enhanced biomass hydrolysis is the conversion of cellulose fibers
      from the cellulose I to the cellulose II crystal phase.

PMID- 21740056
TI  - Uptake and intracellular fate of multifunctional nanoparticles: a comparison
      between lipoplexes and polyplexes via quantum dot mediated Forster resonance
      energy transfer.
AB  - Lipoplexes and polyplexes represent the two major nanocarrier systems for nucleic
      acid delivery. Previous studies examining their uptake and intracellular
      unpacking rely on organic fluorophores fraught with low signal intensity and
      photobleaching. In this work quantum dot mediated Forster resonance energy
      transfer (QD-FRET) was first used to study and compare the cellular uptake and
      the intracellular fate of oligodeoxynucelotide (ODN)-based lipoplexes and
      polyplexes. QD605-amine and Cy5-labeled ODN (Cy5-GTI2040) were chosen as the FRET
      pair. By adjusting the lipid/ODN ratio of lipoplexes and the nitrogen/phosphate
      (N/P) ratio of polyplexes, lipoplexes and polyplexes with comparable physical
      properties were produced. The biological activities of dual-labeled lipoplexes
      and polyplexes remained unaltered compared to their unlabeled counterparts as
      evidenced by their comparable antisense activities against protein R2 in KB
      cells. Flow cytometry and confocal microscopy revealed similar pattern of uptake
      for these two types of nanoparticles, although polyplexes had a higher
      dissociation rate than lipoplexes in KB cells. We demonstrate that QD-FRET is a
      sensitive tool to study the uptake and intracellular unpacking of lipoplexes and
      polyplexes, which may help optimize their formulations for various theranostics
      applications.

PMID- 21740059
TI  - Multivalent bifunctional chelator scaffolds for gallium-68 based positron
      emission tomography imaging probe design: signal amplification via multivalency.
AB  - The role of the multivalent effect has been well recognized in the design of
      molecular imaging probes toward the desired imaging signal amplification.
      Recently, we reported a bifunctional chelator (BFC) scaffold design, which
      provides a simple and versatile approach to impart multivalency to radiometal
      based nuclear imaging probes. In this work, we report a series of BFC scaffolds
      ((t)Bu(3)-1-COOH, (t)Bu(3)-2-(COOH)(2), and (t)Bu(3)-3-(COOH)(3)) constructed on
      the framework of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for (68)Ga
      based PET probe design and signal amplification via the multivalent effect. For
      proof of principle, a known integrin alpha(v)beta(3) specific ligand (c(RGDyK))
      was used to build the corresponding NOTA conjugates (H(3)1, H(3)2, and H(3)3),
      which present 1-3 copies of c(RGDyK) peptide, respectively, in a systematic
      manner. Using the integrin alpha(v)beta(3) binding affinities (IC(50) values),
      enhanced specific binding was observed for multivalent conjugates (H(3)2: 43.9 +/
      16.1 nM; H(3)3: 14.7 +/- 5.0 nM) as compared to their monovalent counterpart
      (H(3)1: 171 +/- 60 nM) and the intact c(RGDyK) peptide (204 +/- 76 nM). The
      obtained conjugates were efficiently labeled with (68)Ga(3+) within 30 min at
      room temperature in high radiochemical yields (>95%). The in vivo evaluation of
      the labeled conjugates, (68)Ga-1, (68)Ga-2, and (68)Ga-3, was performed using
      male severe combined immunodeficiency (SCID) mice bearing integrin
      alpha(v)beta(3) positive PC-3 tumor xenografts (n = 3). All (68)Ga-labeled
      conjugates showed high in vivo stability with no detectable metabolites found by
      radio-HPLC within 2 h postinjection (p.i.). The PET signal amplification in PC-3
      tumor by the multivalent effect was clearly displayed by the tumor uptake of the
      (68)Ga-labeled conjugates ((68)Ga-3: 2.55 +/- 0.50%ID/g; (68)Ga-2: 1.90 +/-
      0.10%ID/g; (68)Ga-1: 1.66 +/- 0.15%ID/g) at 2 h p.i. In summary, we have designed
      and synthesized a series of NOTA-based BFC scaffolds with signal amplification
      properties, which may find potential applications as diagnostic gallium
      radiopharmaceuticals.

PMID- 21740066
TI  - Combining high-energy C-trap dissociation and electron transfer dissociation for
      protein O-GlcNAc modification site assignment.
AB  - Mass spectrometry-based studies of proteins that are post-translationally
      modified by O-linked beta-N-acetylglucosamine (O-GlcNAc) are challenged in
      effectively identifying the sites of modification while simultaneously sequencing
      the peptides. Here we tested the hypothesis that a combination of high-energy C
      trap dissociation (HCD) and electron transfer dissociation (ETD) could
      specifically target the O-GlcNAc modified peptides and elucidate the amino acid
      sequence while preserving the attached GlcNAc residue for accurate site
      assignment. By taking advantage of the recently characterized O-GlcNAc-specific
      IgG monoclonal antibodies and the combination of HCD and ETD fragmentation
      techniques, O-GlcNAc modified proteins were enriched from HEK293T cells and
      subsequently characterized using the LTQ Orbitrap Velos ETD (Thermo Fisher
      Scientific) mass spectrometer. In our data set, 83 sites of O-GlcNAc modification
      are reported with high confidence confirming that the HCD/ETD combined approach
      is amenable to the detection and site assignment of O-GlcNAc modified peptides.
      Realizing HCD triggered ETD fragmentation on a linear ion trap/Orbitrap platform
      for more in-depth analysis and application of this technique to other post
      translationally modified proteins are currently underway. Furthermore, this
      report illustrates that the O-GlcNAc transferase appears to demonstrate
      promiscuity with regards to the hydroxyl-containing amino acid modified in short
      stretches of primary sequence of the glycosylated polypeptides.

PMID- 21740069
TI  - Bimodal quantitative monitoring for enzymatic activity with simultaneous signal
      increases in 19F NMR and fluorescence using silica nanoparticle-based molecular
      probes.
AB  - We describe the bimodal quantitative assay for enzymatic activity in (19)F NMR
      spectroscopy and fluorescence spectroscopy using a nanoparticle-based molecular
      probe. Perfluorinated dendrimers were tethered on silica nanoparticles with a
      phosphate-caged fluorescein as a linker. Before enzymatic reaction, the molecular
      rotation of the perfluorinated dendrimers should be highly restricted, and the
      (19)F NMR signals from the perfluorinated dendrimers were too broad to be
      detected relative to the noise level. Fluorescence signals of fluorescein were
      suppressed by the presence of the diphosphate groups. Following the enzymatic
      reaction with an alkaline phosphatase, perfluorinated dendrimers and fluorescein
      were released, and the NMR signals of perfluorinated dendrimers and strong
      fluorescence from fluorescein were correspondingly observed. The enzymatic
      activity and reaction rates of the hydrolysis of alkaline phosphatase were
      detected from the increases of fluorescence and (19)F NMR signals. Finally, the
      feasibility of the probe in the presence of miscellaneous molecules under
      biomimetic conditions was demonstrated by determining of the enzymatic activity
      in cell lysate. Quantitative analysis using both (19)F NMR spectroscopy and
      fluorescence spectroscopy can be accomplished.

PMID- 21740071
TI  - Pyrene-based materials for organic electronics.

PMID- 21740070
TI  - Exceptional superhydrophobicity and low velocity impact icephobicity of acetone
      functionalized carbon nanotube films.
AB  - We present a simple method to produce carbon nanotube-based films with
      exceptional superhydrophobicity and impact icephobicity by depositing acetone
      treated single-walled carbon nanotubes on glass substrates. This method is
      scalable and can be adopted for any substrate, both flexible and rigid. These
      films have indicated a high contact angle, in the vicinity of 170 degrees ,
      proved both by static and dynamic analysis processes. The dynamic evaporation
      studies indicated that a droplet deposited on the treated films evaporated in the
      constant contact angle mode for more than 80% of the total evaporation time,
      which is definitely a characteristic of superhydrophobic surfaces. Furthermore,
      the acetone-functionalized films showed a strong ability to mitigate ice
      accretion from supercooled water droplets (-8  degrees C), when the droplets were
      found to bounce off the films tilted at 30 degrees . The untreated nanotube films
      did not indicate similar behavior, and the supercooled water droplets remained
      attached to the films' surfaces. Such studies could be the foundation of highly
      versatile technologies for both water and ice mitigation.

PMID- 21740072
TI  - In vivo-in vitro-in silico pharmacokinetic modelling in drug development: current
      status and future directions.
AB  - Although clinical drug trials are indispensable in providing an appropriate
      background for dosage recommendations, they can provide mechanistic
      pharmacokinetic information only indirectly with the help of certain biomarkers
      for pathological, physiological and pharmacological determinants. Thus, to
      provide such mechanistic information of clinical value, various in vitro and in
      silico tests and approaches are increasingly employed in drug discovery and
      development. Integration of the results of these primarily preclinical studies
      has been made possible by various computational models, such as in vitro-in vivo
      extrapolation of hepatic clearance or physiologically based pharmacokinetic
      modelling. In this article, the current status of these modelling approaches is
      surveyed and some examples are given, highlighting advantages and disadvantages
      in applying them at various phases of drug development. A new paradigm of model
      based drug development is briefly described, and the importance of the approach
      of integrating all of the information coming from different investigations at all
      levels--be it in vivo, in vitro or in silico--is emphasized.

PMID- 21740063
TI  - Molecular dynamics simulations reveal the protective role of cholesterol in beta
      amyloid protein-induced membrane disruptions in neuronal membrane mimics.
AB  - Interactions of beta-amyloid (Abeta) peptides with neuronal membranes have been
      associated with the pathogenesis of Alzheimer's disease (AD); however, the
      molecular details remain unclear. We used atomistic molecular dynamics (MD)
      simulations to study the interactions of Abeta(40) and Abeta(42) with model
      neuronal membranes. The differences between cholesterol-enriched and depleted
      lipid domains were investigated by the use of model phosphatidylcholine (PC)
      lipid bilayers with and without 40 mol % cholesterol. A total of 16 independent
      200 ns simulation replicates were investigated. The surface area per lipid,
      bilayer thickness, water permeability barrier, and lipid order parameter, which
      are sensitive indicators of membrane disruption, were significantly altered by
      the inserted state of the protein. We conclude that cholesterol protects Abeta
      induced membrane disruption and inhibits beta-sheet formation of Abeta on the
      lipid bilayer. The latter could represent a two-dimensional (2D) seeding template
      for the formation of toxic oligomeric Abeta in the pathogenesis of AD.

PMID- 21740068
TI  - Discovery and characterization of the Crustacean hyperglycemic hormone precursor
      related peptides (CPRP) and orcokinin neuropeptides in the sinus glands of the
      blue crab Callinectes sapidus using multiple tandem mass spectrometry techniques.
AB  - The crustacean sinus gland (SG) is a well-defined neuroendocrine site that
      produces numerous hemolymph-borne agents including the most complex class of
      endocrine signaling molecules-neuropeptides. Via a multifaceted mass spectrometry
      (MS) approach, 70 neuropeptides were identified including orcokinins,
      orcomyotropin, crustacean hyperglycemic hormone (CHH) precursor-related peptides
      (CPRPs), red pigment concentrating hormone (RPCH), pigment dispersing hormone
      (PDH), proctolin, RFamides, RYamides, and HL/IGSL/IYRamide. Among them, 15 novel
      orcokinins, 9 novel CPRPs, 1 novel orcomyotropin, 1 novel Ork/Orcomyotropin
      related peptide, and 1 novel PDH were de novo sequenced via collision induced
      dissociation (CID) from the SG of a model organism Callinectes sapidus. Electron
      transfer dissociation (ETD) was used for sequencing of intact CPRPs due to their
      large size and higher charge state. Capillary isoelectric focusing (CIEF) was
      employed for separation of members of the orcokinin family, which is one of the
      most abundant neuropeptide families observed in the SG. Collectively, our study
      represents the most complete characterization of neuropeptides in the SG and
      provides a foundation for future investigation of the physiological function of
      neuropeptides in the SG of C. sapidus.

PMID- 21740074
TI  - Prediction of human oral plasma concentration-time profiles using preclinical
      data: comparative evaluation of prediction approaches in early pharmaceutical
      discovery.
AB  - BACKGROUND AND OBJECTIVES: Empirically based methods remain one of our tools in
      human pharmacokinetic predictions. The Dedrick approach and the steady-state
      plasma drug concentration (C(ss))-mean residence time (MRT) approach are based on
      the assumption that concentration-time profiles are similar among species,
      including man, and that curves derived from a variety of animal species can be
      superimposed after mathematical transformation. In the Dedrick approach the
      transformation is based on the slope and intercept of the allometric
      relationship. The C(ss)-MRT approach is based on the implementation of measured
      animal and predicted human MRT and dose/volume of distribution at steady state
      (V(ss)). The aims of the present study were to compare the predictive performance
      of concentration-time profiles obtained by these approaches, to evaluate the
      prediction of individual pharmacokinetic parameters by these approaches and to
      further refine these approaches incorporating the experience from our previous
      work. METHODS: A retrospective analysis using 35 proprietary compounds developed
      at Johnson & Johnson Pharmaceutical Research and Development was conducted to
      compare the accuracies of the Dedrick and C(ss)-MRT approaches for predicting
      oral concentration-time profiles and pharmacokinetic parameters in man. In the
      first step, input for the transformation was based on simple allometry. Then we
      assessed whether both methods could be fine-tuned by systematically incorporating
      correction factors (maximum life span potential, brain weight and plasma protein
      binding), depending on the interspecies relationship. In addition, for the C(ss)
      MRT approach, we used formulas based on multivariate regression analysis as input
      for the transformation. RESULTS: Inclusion of correction factors significantly
      improved the profile predictability for the Dedrick and C(ss)-MRT approaches.
      This was mainly linked to an improved prediction of terminal elimination half
      life (t(1/2)), MRT and the ratio between the maximum plasma concentration and the
      concentration at the last observed time point (C(max)/C(last)). No significant
      differences were observed between the Dedrick approach with correction factors,
      the C(ss)-MRT approach with correction factors and the C(ss)-MRT approach, based
      on the regression equations. CONCLUSIONS: Based on the dataset evaluated in this
      study, we demonstrated that human plasma concentration-time profiles and
      pharmacokinetic parameters could be predicted with the Dedrick and C(ss)-MRT
      approaches and that if correction factors were implemented, the predictions
      improved significantly. With the requirement of only a limited preclinical in
      vivo pharmacokinetic dataset, these empirical methods could offer potential in
      the early stages of drug discovery.

PMID- 21740073
TI  - A reappraisal of current dosing strategies for intravenous fosfomycin in children
      and neonates.
AB  - The rising incidence of multi-drug resistant bacterial pathogens has renewed
      interest in the long-known antibacterial fosfomycin. Not least because of its low
      toxicological potential, there is good clinical experience with intravenous
      fosfomycin for various Gram-positive and Gram-negative infections in the
      treatment of children and neonates. However, the current dosing recommendations
      for intravenous fosfomycin vary widely in paediatric patients. In the present
      review, we summarized available plasma pharmacokinetic data derived from neonates
      or children following intravenous administration of fosfomycin. Subsequently, we
      used this information for recalculation of different dosing strategies and
      simulated a variety of clinically applied dosing regimens. The percentage of time
      above the minimal inhibitory concentration (T>MIC) was calculated for each dosing
      strategy, as this pharmacokinetic-pharmacodynamic parameter was shown to be most
      predictive of antimicrobial and clinical success of fosfomycin treatment. Our
      data corroborate the current practice of selecting the dosage of intravenous
      fosfomycin primarily on the basis of bodyweight and age in paediatric patients.
      As with other 'time-dependent' antibacterials, a dosing interval of 6-8 hours
      should be preferred over 12 hours except for immature neonates. Given a T>MIC
      target of 40-70%, currently recommended dosing strategies appear to be
      insufficient in children aged 1-12 years, if pathogens with MICs of >=32 mg/L are
      suspected and subjects are presenting with normal renal function. Likewise, the
      lowest recommended daily dose for neonates and infants (aged up to 12 months) of
      100 mg/kg bodyweight of fosfomycin should be considered only for pre-term
      neonates with a postmenstrual age below 40 weeks.

PMID- 21740075
TI  - Quantitative prediction of cytochrome P450 (CYP) 2D6-mediated drug interactions.
AB  - BACKGROUND AND OBJECTIVES: An approach was recently proposed for quantitative
      predictions of cytochrome P450 (CYP) 3A4-mediated drug-drug interactions. This
      approach relies solely on in vivo data. It is based on two characteristic
      parameters: the contribution ratio (CR; i.e. the fraction of victim drug
      clearance due to metabolism by a specific CYP) and the inhibition ratio (IR) of
      the inhibitor. Knowledge of these parameters allows forecasting of the ratio
      between the area under the plasma concentration-time curve (AUC) of the victim
      drug when the inhibitor is co-administered and the AUC of the victim drug
      administered alone. The goals of our study were to extend this method to CYP2D6
      mediated interactions, to validate it, and to forecast the magnitude of a large
      number of interactions that have not been studied so far. METHODS: A three-step
      approach was pursued. First, initial estimates of CRs and IRs were obtained by
      several methods, using data from the literature. Second, an external validation
      of these initial estimates was carried out, by comparing the predicted AUC ratios
      with the observed values. Third, refined estimates of CRs and IRs were obtained
      by orthogonal regression in a Bayesian framework. RESULTS: Thirty-nine AUC ratios
      were available for external validation. The mean prediction error of the ratios
      was 0.31, while the mean prediction absolute error was 1.14. Seventy AUC ratios
      were available for the global analysis. Final estimates of CRs and IRs were
      obtained for 39 substrates and 11 inhibitors, respectively. The mean prediction
      error of the AUC ratios was 0.04, while the mean prediction absolute error was
      0.51. CONCLUSIONS: Predictive distributions for 615 possible interactions were
      obtained, giving detailed information on some drugs or inhibitors that have been
      poorly studied so far, such as metoclopramide, bupropion and terbinafine.

PMID- 21740079
TI  - Role of emerging antithrombotic therapy in the prevention of cardioembolic
      complications in patients with atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is
      an independent risk factor of potentially catastrophic cardioembolic strokes. AF
      patients are categorized into high-, intermediate-, and low-risk for
      thromboembolic complications using the CHADS(2) or CHA(2)DS(2)-VASc scoring
      system. Oral anticoagulation using warfarin has been the standard therapy for
      stroke prevention in intermediate- to high-risk AF patients. However, warfarin
      use has been limited by several factors such as narrow therapeutic windows, drug
      drug and drug-food interactions, and hemorrhagic complications. Rigorous research
      evaluated dual antiplatelet therapy of clopidogrel and aspirin (acetylsalicylic
      acid) as a potential alternative to warfarin in the ACTIVE W trial. Dual
      antiplatelet therapy of clopidogrel and aspirin was found to be inferior to
      warfarin in preventing stroke and systemic embolism with increased bleeding risk.
      Other extensive research has led to the development of new antithrombotic agents.
      Recently, dabigatran etexilate 150 mg twice daily, a direct thrombin inhibitor,
      was approved by the US FDA for stroke prevention in patients with non-valvular AF
      after it was found to be superior to warfarin in preventing thromboembolic events
      and associated with less bleeding in the RE-LY trial. It was also cost effective
      when compared with warfarin. Dabigatran can be considered in high-risk AF
      patients who are unable or unwilling to comply with the frequent laboratory and
      clinic visits that are required when receiving treatment with warfarin. Factor Xa
      inhibitors are another class of new anticoagulants that have been developed. Oral
      rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar
      bleeding in the ROCKET-AF trial (HR 0.88; p = 0.117). Apixaban, another factor Xa
      inhibitor, was superior to aspirin in reducing stroke and systemic embolism in
      patients with AF in the AVERROES trial (HR 0.45; p < 0.001). The results of the
      ARISTOTLE trial, which is evaluating apixaban against warfarin in ~18 000
      patients with AF, are expected to be available later this year. Edoxaban, another
      oral factor Xa inhibitor, is currently being evaluated against warfarin in the
      ENGAGE AF-TIMI 48 trial in ~20 000 patients with AF. With these new developments,
      there is a necessity for the clinical practitioner to become familiar with these
      new and upcoming therapies and guidelines. This review provides an overview of
      the available data regarding the clinical usefulness of these agents.

PMID- 21740078
TI  - Fimasartan.
AB  - Fimasartan (BR-A-657; BR-A-657-K; Kanarb(r)), an angiotensin II receptor
      antagonist with selectivity for the AT(1) receptor subtype, is being developed by
      Boryung Pharmaceutical as an oral treatment for hypertension. Fimasartan has been
      approved for use in patients with hypertension in South Korea and has been
      evaluated in three phase III clinical trials (i.e. NCT00922480, NCT01135212, and
      NCT01258673). This review discusses the development history and scientific
      profile of this new compound. This summary has been extracted from Wolters
      Kluwer's Adis R&D Insight drug pipeline database. Adis R&D Insight tracks and
      evaluates drug development worldwide through the entire development process, from
      discovery, through pre-clinical and clinical studies to market launch.

PMID- 21740081
TI  - The correct administration of antihypertensive drugs according to the principles
      of clinical pharmacology.

PMID- 21740076
TI  - HIV/AIDS patients display lower relative bioavailability of efavirenz than
      healthy subjects.
AB  - BACKGROUND: Pharmacokinetic studies of antiretroviral drugs are often conducted
      in adult healthy subjects, and the results are extrapolated to HIV/AIDS patients.
      HIV/AIDS, however, is known to cause morphological and physiological changes that
      may alter the pharmacokinetics of antiretroviral drugs. We examined the effect of
      HIV/AIDS on the pharmacokinetics of efavirenz in Ugandans. METHODS: After a first
      oral dose of efavirenz 600 mg in treatment-naive HIV-infected patients, blood
      samples were collected at nine time points up to 24 hours. The plasma
      concentration time data from these patients were merged with previously reported
      data from adult healthy subjects. Population pharmacokinetic models were fitted
      to the data, using NONMEM VI software. Covariate analyses were performed to
      estimate the effects of HIV/AIDS disease, demographic characteristics (sex,
      bodyweight, age), biochemical variables (serum creatinine, urea, alanine
      aminotransferase) and pharmacogenetic variation in cytochrome P450 (CYP) 2B6,
      CYP3A5 and adenosine triphosphate-binding cassette, sub-family B, member 1
      (ABCB1) on the population pharmacokinetic parameters. RESULTS: Efavirenz plasma
      concentration-time data obtained from 29 HIV-1-infected, treatment-naive patients
      were merged with previously reported data from 32 adult healthy subjects. The
      model identified sex and HIV/AIDS disease as statistically significant
      categorical predictors of efavirenz pharmacokinetics. Females were predicted to
      have a 2-fold higher volume of distribution of the peripheral compartment after
      oral administration (V(2)/F) than males (95% CI 1.53, 2.63), while HIV/AIDS
      patients were found to have 30% lower relative bioavailability (95% CI 18.7,
      40.7) than healthy subjects. The increased V(2)/F in females resulted in a 2-fold
      longer elimination half-life than in males. CONCLUSION: On the basis of the
      findings of this analysis, we conclude that, apart from bodyweight-based
      differences, both HIV/AIDS disease and sex affect efavirenz pharmacokinetics in
      Ugandans. HIV/AIDS disease is associated with reduced relative bioavailability of
      efavirenz. We recommend that findings from healthy subject studies be confirmed
      in HIV/AIDS patients and that caution be applied in direct extrapolation of
      exposure data to the target patient population.

PMID- 21740080
TI  - The authors' reply.

PMID- 21740077
TI  - Randomized, open-label, multicentre pharmacokinetic studies of two dose levels of
      pantoprazole granules in infants and children aged 1 month through <6 years with
      gastro-oesophageal reflux disease.
AB  - BACKGROUND AND OBJECTIVE: The primary objective of this study was to characterize
      the pharmacokinetic profile of pantoprazole delayed-release granules in infants
      and children aged 1 month to <6 years with gastro-oesophageal reflux disease
      (GORD). The studies described in this manuscript were conducted to fulfil the
      requirements of the paediatric written request for pantoprazole by the US FDA.
      METHODS: Two randomized, open-label, multicentre studies were conducted in
      infants aged 1 month to <12 months (study 1) and children aged 1 year through <6
      years (study 2) with GORD. Patients were randomly assigned to either the low-dose
      pantoprazole group (0.6 mg/kg equivalent) or the high-dose pantoprazole group
      (1.2 mg/kg equivalent) in a 1 : 1 fashion. Pantoprazole granules were
      administered approximately 30 minutes before breakfast for at least five
      consecutive doses. Blood samples were obtained at prespecified intervals. Plasma
      pantoprazole concentration-time data were analysed by non-compartmental methods.
      Descriptive statistics were calculated for pharmacokinetic parameters. Patients
      in study 2 additionally received pantoprazole for 28 days. Safety was monitored
      throughout. RESULTS: In study 1, 43 patients were randomized; 42 were included in
      the single-dose pharmacokinetic evaluation (15 females, 27 males; mean postnatal
      age 6.3 months). In study 2, 17 patients were randomized, and all were included
      in the single-dose pharmacokinetic evaluation (6 females, 11 males; mean age 3.2
      years). In both studies, exposure increased with dose. Mean (standard deviation)
      maximum (peak) plasma concentration values for the low and high doses were 503
      (506) ng/mL and 1318 (1307) ng/mL, respectively, in study 1, and 229 (196) ng/mL
      and 653 (645) ng/mL, respectively, in study 2. Area under the plasma
      concentration-time curve values for the low and high doses were 1046 (1043) ng .
      h/mL and 3602 (3269) ng . h/mL, respectively, in study 1, and 293 (146) ng . h/mL
      and 2448 (2170) ng . h/mL, respectively, in study 2. There was a trend for
      increasing clearance with increasing age across the ages 1 month through <6
      years. There was no evidence of drug accumulation after multiple doses. On
      treatment adverse events (AEs) occurred in 19 of 43 patients in study 1 and in 11
      of 17 patients in study 2. Serious AEs occurred in two patients in study 1
      (gastroenteritis in one patient and acute gastroenteritis from rotavirus
      infection resulting in discontinuation of one patient); the serious AEs resolved
      and were not considered by the investigators to be drug related. No other safety
      related discontinuations occurred in either study. CONCLUSIONS: Exposure
      increased with increasing doses of pantoprazole granules, even though wide
      interindividual variability was observed. Compared with that in adults receiving
      pantoprazole 40 mg, exposure obtained with the 1.2 mg/kg dose was similar in
      study 1 and slightly lower in study 2. Pantoprazole was generally well tolerated
      in infants and children aged 1 month through <6 years with GORD. Trial
      registration numbers (ClinicalTrials.gov): NCT00259012 (study 1) and NCT00141817
      (study 2).

PMID- 21740085
TI  - Risk estimation for a malignant transformation of oral lesions by S100A7 and Doc
      1 gene expression.
AB  - The objective of this study was the correlation of Doc-1- and S100A7-gene
      expression in common oral lesions with their cancerous-transformation risk.
      Biopsies (n = 15 each) of healthy gingiva, irritation fibromas, leukoplakias and
      Oral squamous cell carcinoma (OSCCs) were obtained, and after RNA-extraction,
      transcripts of Doc-1 and S100A7 were quantified by RT-PCR. In comparison with the
      healthy gingiva, the expression of Doc-1 was decreased, whereas the expression of
      S100A7 was upregulated in all lesions. As the extent of Doc-1-inactivation and
      S100A7-overexpression is correlated with their biological behavior, the combined
      investigation of both genes could be a promising marker in intraoral lesions to
      estimate the risk for their malignant transformation.

PMID- 21740083
TI  - Antiangiogenic agents for the treatment of nonsmall cell lung cancer:
      characterizing the molecular basis for serious adverse events.
AB  - Novel agents to reduce angiogenesis by targeting vascular endothelial growth
      factor and other proangiogenic signaling pathways are being developed for
      advanced nonsmall cell lung cancer. Antibody-based therapies (e.g., aflibercept)
      and multitargeted tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, and
      BIBF 1120) are being evaluated in phase III clinical trials. Some antiangiogenic
      agents have demonstrated distinct profiles in producing a variety of
      nonhematologic toxicities, including bleeding/hemorrhage, venous and arterial
      thromboembolic events, gastrointestinal perforation, hypertension, and
      proteinuria. Elucidating the molecular basis of these toxicities may lead to
      clinical benefits by improving patient selection and allowing for the development
      of effective prevention and management strategies.

PMID- 21740086
TI  - Tumor necrosis factor-alpha promotes tumor growth by inducing vascular
      endothelial growth factor.
AB  - Tumor necrosis factor (TNF)-alpha has been proved as an adjuvant therapy for
      tumor by FDA. However, the effect of chronic TNF-alpha expression for tumor is
      still controversial. In this study, we investigated the effect of low-dose TNF
      alpha on tumor growth. We confirmed that low-dose TNF-alpha promoted angiogenesis
      of tumor in vivo, vascular endothelial growth factor (VEGF) and hypoxia-inducible
      factor (HIF)-1alpha, the transcription factor of VEGF, were both upregulated. Our
      results suggested that low-dose TNF-alpha was a powerful activator of
      angiogenesis in tumor and HIF-1alpha-VEGF pathway seemed to be the most important
      molecular mechanism.

PMID- 21740087
TI  - Repeated cisplatin treatments inhibit gastrointestinal motility and induces
      baroreflex changes and mechanical hyperalgesia in rats.
AB  - Cisplatin is a chemotherapy agent known for its neurotoxicity. We evaluated the
      effect of cisplatin on the gastric emptying (GE), gastrointestinal (GI) transit
      of liquid, baroreflex function, thermal, and mechanical withdrawal latencies in
      rats. Cisplatin increased the GE of liquid with doses >= 2 mg.kg(-1) by 59.7
      77.4%. This GE delay was not present two weeks after the treatment with five
      doses of cisplatin at 1 mg.kg(-1). Cisplatin also enhanced baroreflex gain
      possibly by increasing sympathetic activity. Our results demonstrated that
      cisplatin (2-10 mg.kg(-1)) causes autonomic neuropathy with GI and baroreflex
      changes and mechanical but not thermal hyperalgesia in rats.

PMID- 21740084
TI  - Three vascular endothelial growth factor polymorphisms (-460C>T, -2578C>A,
      1612G>A) with cancer risk: a meta-analysis based on 30 case-control studies.
AB  - We evaluated cancer risk with three VEGF polymorphisms (-460C>T, -2578C>A,
      1612G>A) based on current available studies. -460C>T did not appear to influence
      cancer risks. -2578C carriers had a 30% reduction of colorectal cancer (CRC) risk
      in comparison with AA homozygote (OR: 0.70, CI: 0.56-0.88). 1612G carriers had a
      striking 84% reduction of gastric cancer risk in comparison with AA homozygote.
      Multiple pair-wise comparisons suggested a recessive role for both -2578A and
      1612A risk allele. Further studies with larger samples, well-matched controls and
      homogenous ethnic background are warranted to confirm these findings. We
      recommend more efforts into the investigation of 1612G>A with cancer risks.

PMID- 21740082
TI  - Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia
      cell lines.
AB  - In this work, effects of bortezomib on apoptosis, clonal progenitor growth,
      cytokine production, and NF-kappaB expression in patients with MDS with
      cytopenias requiring transfusion support are examined. Bortezomib increased
      apoptosis in marrow mononuclear cells but had no effects on CFU-GM, BFU-E, or CFU
      L content. No consistent effects on NF-kappaB activation in vivo were noted. To
      further define the role of bortezomib in AML and MDS, we examined it in
      combination with several targeted agents and chemotherapeutic agents in vitro.
      Combinations with arsenic trioxide, sorafenib, and cytarabine demonstrated
      synergistic in vitro effects in AML cell lines.

PMID- 21740089
TI  - New treatment of cellulite with infrared-LED illumination applied during high
      intensity treadmill training.
AB  - Phototherapy improves cellular activation which is an important factor for the
      treatment of cellulite. The objective of this research was to develop and
      evaluate the effects of a new (noninvasive and nonpharmacological) clinical
      procedure to improve body aesthetics: infrared-LED (850 nm) plus treadmill
      training. Twenty women (25-55 years old) participated in this study. They were
      separated in two groups: the control group, which carried out only the treadmill
      training (n = 10), and the LED group, with phototherapy during the treadmill
      training (n = 10). The training was performed for 45 minutes twice a week over 3
      months at intensities between 85% and 90% maximal heart rate (HR(max)). The
      irradiation parameters were 39 mW/cm(2) and a fluence of 106 J/cm(2). The
      treatment was evaluated by interpreting body composition parameters, photographs
      and thermography. This was primarily a treatment for cellulite with a reduction
      of saddlebag and thigh circumference. At the same time, the treadmill training
      prevented an increase of body fat, as well as the loss of lean mass. Moreover,
      thermal images of the temperature modification of the thighs are presented. These
      positive effects can result in a further improvement of body aesthetics using
      infrared-LED together with treadmill training.

PMID- 21740091
TI  - Comparison of traditional and novel tableting excipients: physical and compaction
      properties.
AB  - CONTEXT: Novel tableting excipients are continuously developed and advertised
      with superior flow and compaction characteristics. OBJECTIVE: The objective of
      this study was to compare two traditionally used and two novel tableting
      excipients with regard to their physical and tableting properties as well as
      their magnesium stearate sensitivity. Avicel((r)) PH102 (microcrystalline
      cellulose) was compared to the novel co-processed excipient Prosolv((r)) SMCC90
      (silicified microcrystalline cellulose), whereas Anhydrous Emcompress((r))
      (anhydrous dicalcium phosphate) was compared to the novel spherically granulated
      excipient Fujicalin((r)) (anhydrous dicalcium phosphate). MATERIALS AND METHODS:
      True density, particle size, specific surface area (SSA), flowability,
      tabletability, and magnesium stearate sensitivity of the excipients was
      determined. RESULTS AND DISCUSSION: Due to the silification process
      (Prosolv((r))) and the unique manufacturing process (Fujicalin((r))), the novel
      excipients showed a comparably larger SSA. Hardest tablets by far could be
      obtained with Prosolv((r)), followed by Avicel((r)) and Fujicalin((r)).
      Avicel((r)) and Prosolv((r)) were sensitive to magnesium stearate, whereas
      Fujicalin((r)) and Emcompress((r)) did not show lubricant sensitivity. This
      confirms the plastic deformation behavior of microcrystalline cellulose and the
      brittle fracture of anhydrous dicalcium phosphate. CONCLUSION: Compared to the
      traditional excipients the investigated novel tableting excipients were
      advantageous with regard to their SSA and their tableting properties.

PMID- 21740092
TI  - Healthcare providers' perspectives on an interprofessional education intervention
      for promoting community re-engagement post stroke.

PMID- 21740093
TI  - Improving interprofessional practice for vulnerable older people: gaining a
      better understanding of vulnerability.
AB  - A key focus for professionals working with older people in the community is on
      those who are vulnerable, although this vulnerability is not well defined. This
      study sought the views of health and social care professionals and older people
      on vulnerability, identifying significant differences between professional and
      older people's perspectives. It found that for older people, vulnerability is an
      emotional response to being in a specific situation, whereas for professionals,
      the vulnerability of those on their case loads relates to them having certain or
      a combination of characteristics (physical, psychological and social). The paper
      concludes that interprofessional care for older people in the community could be
      improved firstly by asking older people if they ever feel vulnerable and if so,
      in what situations and secondly by focusing team efforts on addressing the issues
      raised by older people in response to these questions.

PMID- 21740094
TI  - Chemical composition, antioxidant activity and larvicidal effects of essential
      oil from leaves of Apium graveolens.
AB  - The leaves of Apium graveolens were extracted and the essential oil composition,
      immunotoxicity effects, and antioxidant activity were studied. The analyses were
      conducted by gas chromatography and mass spectroscopy (GC-MS), which revealed the
      essential oils of A. graveolens leaves. Twenty-eight components, representing
      73.72% of the total oil were identified from the leaves. The major components are
      4-chloro-4,4-dimethyl-3-(1-imidazolyl)-valerophenone (19.90%), 1-dodecanol
      (16.55%), 9-octadecen-12-ynoic acid, methyl ester (4.93%), ethyl 4,4-D2-N-hexyl
      ether (4.11%), 3-(hydroxymethyl)-1-phenyl-1-heptadecyn-3-ol (3.28%), 1,4-methano
      1H-indene, octahydro-4-methyl-8-methylene-7-(1-methylethyl)-, [1S
      (1alpha,3alphaalpha,4alpha,7alpha,7alphaalpha)]- (2.99%), 3,4-dihydro-2H-1,5-(3"
      t-butyl)benzodioxepine (2.56%), Z-10-tetradecen-1-ol acetate (2.53%), 9H
      pyrrolo[3',4':3,4]pyrrolo[2,1-alpha]phthalazine-9, 11(10H)-dione, 10-ethyl-8
      phenyl (2.07%). The leaf oil had significant toxic effects against the larvae of
      A. aegypti with an LC(50) value of 59.32 ppm and an LC(90) value of 127.69 ppm.
      The essential oil from the A. graveolens leaves was investigated for scavenging
      of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical activity and the results
      demonstrate that the essential oil from the A. graveolens has potential as a
      natural antioxidant and thus inhibit unwanted oxidation process. The above data
      indicate that the major compounds may play an important role in the toxicity of
      essential oils and also as natural antioxidant.

PMID- 21740095
TI  - Quality of life appears similar between survivors of indolent and aggressive non
      Hodgkin lymphoma.
AB  - Few studies have examined the quality of life (QOL) in survivors of non-Hodgkin
      lymphoma (NHL). A total of 109 patients with NHL (58 aggressive [AGG], 51
      indolent [IND]) completed two health-related QOL assessments using the Medical
      Outcomes Study 36-Item Short-Form Healthy Survey (MOS SF-36) and the Functional
      Assessment in Cancer Therapy - Fatigue (FACT-F). Scores between IND and AGG were
      compared using a two-sample t-test. Multiple linear regression was performed to
      account for any potentially explanatory variables. Overall, 70.6% had received
      chemotherapy and 55% had received immunotherapy. Some 17.6% of the IND group had
      received no therapy. The overall physical and mental component QOL scores of the
      SF-36 did not differ between survivors. Physical function in survivors of IND was
      significantly better when compared with that of AGG NHL. Our study reports a
      similar overall QOL between survivors of IND and AGG NHL. Physical function,
      however, may be more impaired in survivors of AGG NHL.

PMID- 21740096
TI  - Multi-parameter prognostication in chronic lymphocytic leukemia.

PMID- 21740097
TI  - Durable event-free survival following autologous stem cell transplant for
      relapsed or refractory follicular lymphoma: positive impact of recent rituximab
      exposure and low-risk Follicular Lymphoma International Prognostic Index score.
AB  - Published studies have provided conflicting results regarding the curative
      potential of high dose chemotherapy and autologous stem cell transplant
      (HDT/ASCT) for follicular lymphoma (FL). Our objectives were to evaluate the long
      term event-free (EFS) and overall (OS) survival rates following ASCT for FL, and
      to identify predictors of improved outcome. We conducted a retrospective analysis
      of the first 100 consecutive patients with relapsed or refractory FL treated with
      HDT/ASCT in Calgary from 1993 to 2008. With a median follow-up of 65 months
      (range 16-178) post-ASCT, 5-year EFS and OS rates were 56% (95% confidence
      interval [CI] 46-66%) and 70% (95% CI 61-79%), respectively. A plateau on the EFS
      curve is evident starting 6 years post-ASCT. Also, the EFS post-ASCT was markedly
      longer than the 12-month median EFS from last therapy prior to ASCT (p < 0.0001).
      Failure of rituximab pre-ASCT was not associated with EFS or OS. Severe
      toxicities included two early treatment-related deaths, and four late deaths from
      secondary leukemia. Independent predictors of EFS and OS in multivariate analysis
      were rituximab therapy within 6 months of ASCT, chemosensitivity and FLIPI (FL
      International Prognostic Index) score 0-1. In conclusion, our data suggest that
      over 50% of patients with relapsed/refractory FL who have failed 1-2 prior
      chemotherapy regimens achieve long-term EFS following HDT/ASCT.

PMID- 21740098
TI  - Development and evaluation of tripalmitin emulsomes for the treatment of
      experimental visceral leishmaniasis.
AB  - The antifungal and antileishmanial agent amphotericin B (AmB) was formulated in
      tripalmitin based nanosize lipid partices (emulsomes) for macrophage targeting
      for the treatment of visceral leishmaniasis (VL). Emulsomes were modified by
      coating them with macrophage-specific ligand (O-palmitoyl mannan, OPM). The
      antileishmanial activity of AmB (0.5 and 1 mg/kg) was investigated in-vivo
      against VL by the inhibition of parasitic load in the spleen of L. donovani
      infected hamsters after intraperitoneal injections of AmB-Doc (Mycol), plain
      emulsomes (TPEs) and OPM coated emulsomes (TPEs-OPM). The formulations were found
      to be less effective at the dose of 0.5 mg/kg. At the dose of 1 mg/kg,
      formulation TPEs-OPM eliminated intracellular amastigotes of L. donovani within
      splenic macrophages more efficiently (62.76 +/- 3.54 % parasite inhibition) than
      the formulation TPEs (42.68 +/- 2.36 % parasite inhibition) (P < 0.01) or AmB-Doc
      (25.87 +/- 3.87 % parasite inhibition) (P < 0.001). Our results suggest that
      these formulations (plain and ligand grafted emulsomes) are a promising
      substitute to the conventional AmB-Doc formulation for the treatment of VL.

PMID- 21740099
TI  - Inhibition of carbonic anhydrase isozymes I and II with natural products
      extracted from plants, mushrooms and honey.
AB  - Different natural products and secondary metabolites from mushrooms, teas,
      honeys, mosses, plants and seaweeds were investigated for their in vitro
      inhibitory effects on human carbonic anhydrase (hCA, E.C.4.2.1.1) isoforms I and
      II. Inhibition data were correlated with the total phenol content in the extract
      and investigated with the pure compounds believed to be responsible for this
      activity. Methanolic extracts were prepared for 17 such pure chemicals present in
      the natural products and for 41 diverse natural products. The IC(50) values were
      in the range of 0.11-66.50 MUg/mL against hCA I and of 0.09-54.54 MUg/mL against
      hCA II, respectively. The total phenol content was in the range of 0.02-1318.96
      (as milligrams of gallic acid equivalents) per gram of sample. These data offer
      new insights on possible novel classes of CA inhibitors based on natural
      products, possessing a range of chemical structures not present in the classical
      inhibitors with pharmacological applications, such as the sulfonamides and
      sulfamates.

PMID- 21740100
TI  - A new class of 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl
      (piperidinyl)-1,3,5-triazine analogues with antimicrobial/antimycobacterial
      activity.
AB  - This study presents the synthesis and in vitro pharmacological evaluations of
      novel 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl
      (piperidinyl)-1,3,5-triazines. The title compounds were assayed for their in
      vitro antimicrobial activity against eight bacteria (Staphylococcus aureus,
      Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae,
      Salmonella typhi, Proteus vulgaris, Shigella flexneria) and four fungi
      (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida
      albicans) using paper disc diffusion and agar streak dilution method as well as
      against Mycobacterium tuberculosis H37Rv strain using BACTEC MGIT and Lowenstein
      Jensen MIC method. The bioassay results indicate that nine compounds namely 5d,
      5h, 5n, 5p, 5q, 5r, 5s, 5t and 5u could be considered as possible potential
      agents with dual antimicrobial and antimycobacterial activities. The structures
      of the compounds were elucidated with the aid of IR, (1)H NMR, (13)C NMR, (19)F
      NMR spectroscopy and CHN analysis.

PMID- 21740101
TI  - Designing modulators of dimethylarginine dimethylaminohydrolase (DDAH): a focus
      on selectivity over arginase.
AB  - DDAH inhibition presents a novel promising pharmaceutical strategy to lower NO
      formation. To date, several potent DDAH inhibitors have been published, most of
      them representing analogues of l-arginine. While inhibitory effects on NOSs have
      already been considered, selectivity over arginase has been neglected so far. In
      our view, the latter selectivity is more important since an additional inhibition
      of arginase decreases the desired effects on NO levels. Thus, we particularly
      focus on selectivity over arginase. We present a comprehensive selectivity
      profile of known DDAH inhibitors by covering their inhibitory potency on
      arginase. Among the studied compounds, N(omega)-(2-methoxyethyl)-l-arginine (2a,
      L-257) that is already selective over NOSs also only modestly affected arginase
      activity and is thus far the most suitable DDAH inhibitor for pharmacological
      studies.

PMID- 21740102
TI  - Synthesis and antioxidant activity evaluations of melatonin-based analogue indole
      hydrazide/hydrazone derivatives.
AB  - Melatonin (MLT) is a hormone synthesized from the pineal gland. It is a direct
      scavenger of free radicals, which is related to its capability to defend cells
      from oxidative stress. Recently MLT-related compounds are under investigation to
      establish which exhibit the maximum activity with the lowest side effects. In
      this study 5-chloroindole hydrazide/hydrazone derivatives were synthesized from 5
      chloroindole-3-carboxaldehyde and phenyl hydrazine derivatives. All the compounds
      characterized and in vitro antioxidant activity was investigated against MLT and
      BHT. Most of the compounds showed strong inhibitory effect on the superoxide
      radical scavenging assay at 1 mM concentration (79 to 95%). Almost all the tested
      compounds possessed strong scavenging activity against the DPPH radical
      scavenging activity with IC(50) values (2 to 60 uM). Lastly, compound 1j revealed
      stronger inhibitory activity against MLT in the LP inhibitory assay at 0.1mM
      concentration (51%) while the rest of the compounds showed moderate inhibition.

PMID- 21740103
TI  - Synthesis and antidiabetic activity of morpholinothiazolyl-2,4-thiazolidindione
      derivatives.
AB  - We report the synthesis and the in vitro insulin releasing and glucose uptake
      activity of the morpholino thiazolyl-2,4-thiazolidinediones (1-15). Compounds 5,
      11-15 (at lower concentration; 0.001 mg/ml) were able to increase insulin release
      in the presence of 5.6 mmol/l glucose. The compounds, except derivative 3 show an
      increase of glucose uptake. Various compounds are interesting potential
      antidiabetic leads showing pancreatic and extrapancreatic effects.

PMID- 21740104
TI  - Chemical constituents of Polygala tenuifolia roots and their inhibitory activity
      on lipopolysaccharide-induced nitric oxide production in BV2 microglia.
AB  - A methanolic extract of the roots of Polygala tenuifolia (Polygalaceae)
      significantly attenuated nitric oxide (NO) production in lipopolysaccharide (LPS)
      stimulated BV2 microglia cells. Five xanthones, 1-hydroxy-7-methoxyxanthone (1),
      3,6-dihydroxy-1,2,7-trimethoxyxanthone (2), 1,3,6-trihydroxy-2,7
      dimethoxyxanthone (3), 1,7-dihydroxy-2,3-dimethoxyxanthone (4) and 1,7-dihydroxy
      3-methoxyxanthone (5), and five phenylpropanoids, 4-hydroxy-3
      methoxypropiophenone (6), methyl 4-hydroxy-3-methoxycinnamic acid (7), 3,4,5
      trimethoxycinnamic acid (8), 4-methoxycinnamic acid (9) and beta-d-(3-O-sinapoyl)
      fructofuranosyl-alpha-d-(6-O-sinapoyl)glucopyranoside (10), were isolated from
      CHCl(3) fraction using bioactivity-guided fractionation. Among these compounds,
      compounds 1, 2, 4, 5 and 7 showed significant inhibitory effects on LPS-induced
      NO production in BV2 microglia cells at the concentration ranging from 10.0 to
      100.0 MUM.

PMID- 21740106
TI  - A screening assay for neuraminidase inhibitors using neuraminidases N1 and N3
      from a baculovirus expression system.
AB  - CONTEXT: Development of inexpensive and safe enzymatic assays to screen for
      putative neuraminidase inhibitors. OBJECTIVE: Validate the use of recombinant
      neuraminidase expressed in baculovirus located on the viral surface capsule to
      develop a neuraminidase inhibitor screening assay. MATERIALS AND METHODS:
      Recombinant baculovirus particles displaying neuraminidase N1 and N3 were used as
      enzyme sources. The assay set-up required the use of 2'-(4-methylumbelliferyl)
      alpha-D-acetyl neuraminic acid as substrate and oseltamivir carboxylate as
      benchmark inhibitor. RESULTS: The assay was set up in a standard 96-well plate.
      The within- and between-assay coefficients of variation were, on average, less
      than 10%. The 50% inhibitory concentration values of the inhibitor were in good
      agreement with those determined by independent kinetic experiments. DISCUSSION
      AND CONCLUSIONS: The assay showed satisfactory within- and between-assay
      repeatability. The obtained results suggest that recombinant baculovirus
      expressing neuraminidase located on the virus membrane capsule can be used to set
      up affordable and reliable neuraminidase inhibitors screening assays.

PMID- 21740105
TI  - In vitro effects of some drugs on human erythrocyte glutathione reductase.
AB  - The effects of ketotifen, meloxicam, phenyramidol-HCl and gadopentetic acid on
      the enzyme activity of GR were studied using human erythrocyte glutathione
      reductase (GR) enzymes in vitro. The enzyme was purified 209-fold from human
      erythrocytes in a yield of 19% with 0.31 U/mg. The purification procedure
      involved the preparation of haemolysate, ammonium sulphate precipitation, 2'',5'
      ADP Sepharose 4B affinity chromatography and Sephadex G-200 gel filtration
      chromatography. Purified enzyme was used in the in vitro studies. In the in vitro
      studies, IC(50) values and K(i) constants were 0.012 mM and 0.0008 +/- 0.00021 mM
      for ketotifen; 0.029 mM and 0.0061 +/- 0.00127 mM for meloxicam; 0.99 mM and
      0.4340 +/- 0.0890 mM for phenyramidol-HCl; 138 mM and 28.84 +/- 4.69 mM for
      gadopentetic acid, respectively, showing the inhibition effects on the purified
      enzyme. Phenyramidol-HCl showed competitive inhibition, whereas the others showed
      non-competitive inhibition.

PMID- 21740107
TI  - Design and characterization of calcium alginate microparticles coated with
      polycations as protein delivery system.
AB  - Bovine serum albumin (BSA) loaded calcium alginate microparticles (MPs) produced
      in this study by a w/o emulsification and external gelation method exhibited
      spherical and fairly smooth and porous morphology with 1.052 +/- 0.057 um modal
      particle size. The high permeability of the calcium alginate hydrogel lead to a
      potent burst effect and too fast protein release. To overcome these problems, MPs
      were coated with polycations, such as chitosan, poly-L-lysine and DEAE-dextran.
      Our results demonstrated that coated MPs showed slower release and were able to
      significantly reduce the release of BSA in the first hour. Therefore, this method
      can be applied to prepare coated alginate MPs which could be an optimal system
      for the controlled release of biotherapeutic molecules. Nevertheless, further
      studies are needed to optimize delivery properties which could provide a
      sustained release of proteins.

PMID- 21740108
TI  - Targeting the peroxisome proliferator-activated receptors (PPARs) in spinal cord
      injury.
AB  - INTRODUCTION: Traumatic spinal cord injury (SCI) causes severe and permanent
      functional deficits, due to the primary mechanical insult, followed by secondary
      tissue degeneration. The direct damage is followed by a second phase of tissue
      degeneration, which may take place over a period of weeks or even months, causing
      neuronal and axonal destruction. A key mediator of this process is an acute and
      robust inflammatory response, which involves the synthesis and release of
      chemokines and cytokines, and a coordinated recruitment of circulating
      leucocytes, as well as microglia, from the CNS parenchyma. The search for a
      'cure' for SCI has yet to produce a convincingly efficacious treatment that
      improves the outcome for patients. AREAS COVERED: This review explores the
      experimental studies describing the beneficial effects of PPAR receptor
      modulators in spinal cord trauma. EXPERT OPINION: Because of safety issues and
      limited data, PPAR agonists are not yet included in SCI-related treatment
      strategies. PPAR agonists for specific isoforms (alpha, beta/delta and gamma)
      have demonstrated both anti-inflammatory and immunomodulatory properties.
      Pharmacological activation of PPAR can be considered as a multi-faceted
      therapeutic target, due to its anti-inflammatory/antioxidant/anti-excitotoxic/pro
      energetic profile, reported in some neurological and inflammatory-related
      diseases.

PMID- 21740109
TI  - Vitamin D deficiency, statin-related myopathy and other links with vascular risk.

PMID- 21740110
TI  - Urodynamic assessment of children treated with botulinum toxin A injections for
      urge incontinence: a pilot study.
AB  - OBJECTIVE: This study aimed to investigate changes in urodynamic findings and
      symptoms after detrusor injections of botulinum toxin A (BTX-A) in children with
      idiopathic detrusor overactivity (IDO) and urge incontinence. MATERIAL AND
      METHODS: Eight girls and five boys, aged 7-19 years, who had urge incontinence
      refractory to scheduled voiding and anticholinergics, were included this
      prospective study. Urodynamic studies showed postoperative IDO in 12 patients. A
      dose of 50-100 IU (1.3 -- 4.8 IU/kg) BTX-A was primarily administered at 15-20
      detrusor sites. A control urodynamic study was performed within 3 months after
      the injections. Seven patients had a repeated procedure 16 (range 6-24) months on
      the average after the first one. RESULTS: Eleven of the 13 patients had daily
      incontinence and two had incontinence a couple of times a week in association
      with urge symptoms. Postoperatively, no patient had urinary retention, but one
      girl had a urinary tract infection 4 months after the therapy. Five patients had
      a full response, seven partial responses and one no response 1-3 months after the
      first treatment. After 1 year, three of nine patients still have full response.
      Maximum cystometric capacity increased after the first treatment from a median of
      227 ml to 379 ml (p = 0.005) and the number of patients with uninhibited detrusor
      contractions more than 30 cmH2O during the filling phase decreased from eight to
      two out of 13 (p = 0.041). CONCLUSIONS: Intradetrusor BTX-A injections
      effectively reduce day-time wetting, significantly increase bladder volume and
      decrease detrusor overactivity in children with urge incontinence refractory to
      scheduled voidings and anticholinergics.

PMID- 21740112
TI  - Grammatical gender in German: a case for linguistic relativity?
AB  - The "principle of linguistic relativity" holds that, by way of grammatical
      categorization, language affects the conceptual representations of its speakers.
      Formal gender systems are a case in point, albeit a particularly controversial
      one: Previous studies obtained broadly diverging data, thus giving rise to
      conflicting conclusions. To a large extent, this incoherence is related to task
      differences and methodological problems. Here, a priming design is presented that
      avoids previous problems, as it prevents participants from employing gender
      information in a strategic manner. Four experiments with German native speakers
      show priming effects of the prime's grammatical gender on animate and nonanimate
      targets, an effect for the prime's biological gender on animate targets, but no
      effect for the prime's biological gender on nonanimate targets, and thus speak
      against an effect of language on thought for German gender.

PMID- 21740113
TI  - Event-based prospective remembering in a virtual world.
AB  - Most laboratory-based prospective memory (PM) paradigms pose problems that are
      very different from those encountered in the real world. Several PM studies have
      reported conflicting results when comparing laboratory- with naturalistic-based
      studies (e.g., Bailey, Henry, Rendell, Phillips, & Kliegel,  2010 ). One key
      contrast is that for the former, how and when the PM cue is encountered typically
      is determined by the experimenter, whereas in the latter case, cue availability
      is determined by participant actions. However, participant-driven access to the
      cue has not been examined in laboratory studies focused on healthy young adults,
      and its relationship with planned intentions is poorly understood. Here we report
      a study of PM performance in a controlled, laboratory setting, but with
      participant-driven actions leading to the availability of the PM cue. This uses a
      novel PM methodology based upon analysis of participant movements as they
      attempted a series of errands in a large virtual building on the computer screen.
      A PM failure was identified as a situation in which a participant entered and
      exited the "cue" area outside an errand related room without performing the
      required errand whilst still successfully remembering that errand post test.
      Additional individual difference measures assessed retrospective and working
      memory capacity, planning ability and PM. Multiple regression analysis showed
      that the independent measures of verbal working memory span, planning ability,
      and PM were significant predictors of PM failure. Correlational analyses with
      measures of planning suggest that sticking with an original plan (good or bad) is
      related to better overall PM performance.

PMID- 21740114
TI  - Spontaneous otogenic pneumocephalus presenting with occipital subcutaneous
      emphysema as primary symptom: could tension gas cause the destruction of cranial
      bones?
AB  - The authors report, to the best of their knowledge, the first case of a
      spontaneous tension pneumocephalus with subcutaneous emphysema.
      Hyperpneumatization of the cranium and mechanical compression contributed jointly
      to the formation of a fistula, and air pressure caused a subsequent disruption of
      the suture and air leakage into the subcutaneous space. A minimally invasive
      otological procedure proved efficacious for resolution.

PMID- 21740115
TI  - Nodular enhancement within the internal auditory canal following retrosigmoid
      vestibular schwannoma resection: a unique radiological pattern.
AB  - OBJECT: The authors describe the unique occurrence of nodular enhancement within
      the fundus of the internal auditory canal (IAC) lateral to the preoperative
      radiological tumor margin following gross-total vestibular schwannoma (VS)
      resection. METHODS: The nature of the study was a retrospective chart review of
      records. The authors reviewed the cases of all patients who underwent
      microsurgical resection of a VS between January 2000 and January 2010 at a single
      tertiary referral center. Patients with incomplete resection, neurofibromatosis
      Type 2, and those with fewer than 2 postoperative MR images available for review
      were excluded. Postsurgical patients with IAC enhancement located lateral to the
      preoperative imaging-delineated tumor margin were identified. Lesion morphology
      was characterized on serial MR imaging studies. Clinical follow-up and outcomes
      were recorded. RESULTS: Over the past decade, 350 patients underwent
      microsurgical VS resection. Of these, 16 patients met study criteria and were
      found to have postsurgical enhancement in the distal aspect of the IAC lateral to
      the imaging limits of the preoperative tumor margin on the first postoperative MR
      imaging study (37.5% women, median age 45 years). Initial MR imaging was
      performed at a mean of 3.1 months following surgery, and the mean radiological
      follow-up duration was 39.8 months (range 16.4-101.9 months). None of the 16
      patients developed recurrence during the follow-up course. CONCLUSIONS: In
      contrast to previous publications that have reported a high rate of recurrence in
      cases involving nodular enhancement within the original tumor bed, postoperative
      enhancement in the IAC lateral to the original tumor margin appears to carry much
      less risk for tumor recurrence. These findings may be helpful when counseling
      patients on the recommended frequency of postoperative follow-up imaging.

PMID- 21740116
TI  - Glossopharyngeal neuralgia.

PMID- 21740117
TI  - Bilateral subfrontal approach for tuberculum sellae meningiomas in long-term
      postoperative visual outcome.
AB  - OBJECT: Various surgical approaches, such as uni- and bifrontal, frontolateral,
      and pterional approaches, have been advocated for tuberculum sellae meningiomas.
      The authors retrospectively reviewed the effectiveness of a bilateral subfrontal
      approach for tuberculum sellae meningiomas with special attention to
      ophthalmological outcomes and complications. METHODS: Between 1993 and 2009, 34
      patients underwent surgery for removal of tuberculum sellae meningiomas at Osaka
      City University. Tumor size ranged from 14 to 45 mm. Thirty-two of 34 patients
      presented with visual disturbances before the surgery. The visual functions in
      all patients were assessed using a visual impairment score (VIS) before and after
      surgery. Postoperative visual examination was performed 2 weeks after surgery.
      Long-term follow-up examinations were conducted 1 year after surgery. RESULTS:
      Radical resection (Simpson Grades I and II) was accomplished in 27 patients, and
      subtotal or partial resection (Simpson Grades III and IV) was achieved in 7.
      There was no deterioration in postoperative visual outcome. Twenty-nine (90.6%)
      of 32 patients showed improved VIS compared with preoperative VIS. The average
      VIS was 38.1 preoperatively, 23.5 in the short-term postoperative period, and
      21.8 in the long-term postoperative period. In the short-term postoperative
      period, the visual function in 6 patients normalized, and visual problems
      persisted in the remaining 26. Six (23%) of 26 patients showed further
      improvement in VIS during the long-term follow-up period, and no patient
      exhibited a worsened VIS during this time. One patient complained of hyposmia
      after surgery, but there was no indication of related complications such as CSF
      leakage or frontal brain contusion. CONCLUSIONS: The bilateral subfrontal
      approach was previously avoided because of the relatively high rate of
      complications in earlier surgical series of tuberculum sellae meningiomas.
      However, after developments in microsurgical techniques in recent years, the
      bilateral subfrontal approach can now provide satisfactory visual outcomes with
      minimal postoperative complications. Careful preservation of the blood supply to
      optic apparatus and early unroofing of the optic canal using a bilateral
      subfrontal approach led to further improvement in long-term postoperative visual
      outcome.

PMID- 21740118
TI  - Factors associated with delay to pituitary adenoma diagnosis in patients with
      visual loss.
AB  - OBJECT: The duration of visual symptoms associated with a nonfunctioning
      pituitary adenoma (NFA) is a predictive factor for chances of visual improvement.
      The authors investigated factors associated with increased duration of visual
      symptoms in patients with NFAs. METHODS: The authors retrospectively reviewed
      NFAs resected at their institution between 2004 and 2010 for duration of visual
      symptoms, postoperative improvement, and associated factors. RESULTS: Seventy
      five patients underwent NFA resection with a median visual symptom duration of
      6.5 months (range 1 week-15 years). A multivariate logistic regression showed
      that duration of symptoms (p = 0.04), but not age at surgery (p = 0.2), predicted
      postoperative normalization of vision. Univariate nonparametric analyses
      investigating age at symptom onset, sex, race, insurance type, ophthalmological
      conditions, income, marital status, emergency department admission, language, and
      medical provider found that age was the only variable significantly prolonging
      symptom duration (p = 0.04), a finding confirmed by a multivariate regression
      analysis. Patients 20-39, 40-59, and 60-79 years old had median durations of
      symptoms of 4, 7, and 9 months, respectively. Seven older patients had symptoms
      attributed to preexisting ophthalmological conditions for a median of 18 months
      before NFA diagnosis. Among age and race subgroups, the largest difference in
      median symptom duration was between white patients in the 60-79-year age range
      (duration of 5 months) and nonwhite patients in the 60-79-year age range
      (duration of 24 months) (p = 0.04). CONCLUSIONS: The authors found that older age
      was associated with delayed NFA diagnosis in visually impaired patients.
      Contributing factors were the attributing of visual symptoms from NFAs to other
      ophthalmological conditions in these patients, and delayed presentation in
      elderly nonwhite patients. These findings highlight challenges associated with
      timely NFA diagnosis in visually impaired patients, a key factor for chances of
      improvement.

PMID- 21740119
TI  - Case series and efficacy.

PMID- 21740120
TI  - Disparities in care.

PMID- 21740121
TI  - More malfunctioning Medos Hakim programmable valves: cause for concern?
AB  - OBJECT: In recent years, the authors have noticed a growing number of
      programmable valve defects at their institution. Therefore, they conducted this
      study to evaluate the increased incidence of malfunctioning valves. METHODS: They
      investigated all revisions that had been performed at their institution between
      1994 and 2010 for dislodgement of the stator of a standard Medos Hakim
      programmable valve with a prechamber. RESULTS: Fifteen valves were removed
      because of dislodged stators. The valves had been implanted between May 16, 1993,
      and December 27, 2002, and were explanted between February 19, 2006, and January
      22, 2010. Thus, the valves had been in place for a mean period of 11 years
      (median 11 years, range 7-14 years). The percentage of dislodged stators was
      almost 3% (15 of 546 valves). Particularly noteworthy is that all malfunctioning
      valves were found in children who had been younger than 1 year of age at the time
      of implantation. CONCLUSIONS: Medos Hakim programmable valve malfunctions are
      rare events but should receive careful attention. When the pressure setting
      cannot be adjusted, a malfunction should always be suspected and radiographic
      imaging should be performed to assess the valve. Stator dislodgement is the most
      serious form of valve adjustment failure.

PMID- 21740122
TI  - Stereotactic radiosurgery for glossopharyngeal neuralgia: preliminary report of 5
      cases.
AB  - OBJECT: Glossopharyngeal neuralgia (GPN) is a rare pain disorder characterized by
      severe, stabbing pain of the ear, posterior tongue, and throat. The authors
      report their early experience of using stereotactic radiosurgery (SRS) as an
      alternative to posterior fossa surgery for patients with medically resistant GPN.
      METHODS: Five patients (3 men, 2 woman) with medically resistant GPN underwent
      Gamma Knife surgery. The radiosurgical target was the distal portion of the
      glossopharyngeal and vagus nerves at the jugular foramen (glossopharyngeal
      meatus). The maximum radiation dose in all cases was 80 Gy. The median follow-up
      after radiosurgery was 13 months (range 2-19 months). RESULTS: Three patients
      became pain-free at 2 days, 3 days, and 2 weeks, respectively, and were able to
      discontinue the medications taken preoperatively for their pain. None of these
      patients have suffered recurrent pain since becoming pain free. Two patients
      experienced no benefit from the procedure and underwent posterior fossa surgery 2
      and 5 months after SRS. Both of these patients continued to have pain after
      posterior fossa surgery. One of these patients was later discovered to have a
      head and neck cancer as the cause of his pain. No patient developed hoarseness or
      dysphagia after radiosurgery. CONCLUSIONS: This preliminary experience
      demonstrates that SRS is an option for patients with medically resistant GPN.
      Additional follow-up and a larger number of patients are needed to demonstrate
      the long-term safety and optimal radiation dosimetry for this indication.

PMID- 21740123
TI  - Endovascular treatment of symptomatic intracranial stenosis with the Wingspan
      stent system and Gateway PTA balloon: a multicenter series of 60 patients with
      acute and midterm results.
AB  - OBJECT: The limitations of the medical management of symptomatic intracranial
      arterial stenosis (SIAS) have encouraged the development of new strategies, such
      as endovascular treatment. In this study, the authors report and analyze a series
      of 63 endovascular procedures in which the Wingspan stent system was used.
      METHODS: Data from 60 patients presenting with refractory SIAS, treated in 5
      French neurointerventional centers between September 2006 and August 2009, were
      retrieved. An angiogram was systematically obtained 6 months after the procedure
      and yearly thereafter. The clinical neurological status was assessed and reported
      using the modified Rankin scale at 1-month, 6-month, and 1-year follow-up visits.
      RESULTS: A total of 63 stenotic lesions was treated. The mean age of the patients
      was 65.3 years, and the mean diameter of the stenosis was 80.2%. Technical
      success was achieved in 95.2% of cases. The overall incidence of procedural
      complications was 20.6%, with a 4.8% rate of permanent postoperative morbidity
      and death. In-stent restenosis (ISR)/occlusion occurred in 11 cases (17.4%), of
      which 10 were asymptomatic and 9 were detected less than 1 year from the
      endovascular treatment. In 1 case, the patient presented with a recurrent
      transient ischemic attack and was treated again with angioplasty. The mean follow
      up was 13.2 months. CONCLUSIONS: Endovascular treatment of SIAS demonstrates a
      moderate risk of neurological complication. Nevertheless, considering the
      critical natural history of severe refractory lesions, this may be considered the
      first alternative in cases of failed medical therapy. Technical failure, residual
      stenosis, or in-stent restenosis did not lead to systematic recurrent stroke in
      this series, which suggests the importance of plaque stabilization and
      neoendothelialization.

PMID- 21740124
TI  - Trends in the treatment of lumbar spine fractures in the United States: a
      socioeconomics perspective: clinical article.
AB  - OBJECT: The objective of this study was to investigate a national health care
      database and analyze demographics, hospital charges, and treatment trends of
      patients diagnosed with lumbar spine fractures in the US over a 5-year period.
      METHODS: Clinical data were derived from the Nationwide Inpatient Sample (NIS)
      for the years 2003 through 2007. The NIS is maintained by the Agency for
      Healthcare Research and Quality and represents a 20% random stratified sample of
      all discharges from nonfederal hospitals within the US. Patients with lumbar
      spine fractures were identified using the appropriate ICD-9-CM code. Data on the
      number of vertebral body augmentation procedures were also retrieved. National
      estimates of discharges, hospital charges, discharge patterns, and treatment with
      spinal fusion trends were retrieved and analyzed. RESULTS: More than 190,000
      records of patients with lumbar spine fractures were abstracted from the
      database. During the 5-year period, there was a 17% increase in hospitalizations
      for lumbar spine fractures. This was associated with a 27% increase in hospital
      charges and a 55% increase in total national charges (both adjusted for
      inflation). The total health care bill associated with lumbar spine fractures in
      2007 exceeded 1 billion US dollars. During this same time period, there was a 24%
      increase in spinal fusions for lumbar fractures, which was associated with a 15%
      increase in hospital charges. The ratio of spinal fusions to hospitalizations
      (surgical rate) during this period, however, was stable with an average of 7.4%
      over the 5-year period. There were an estimated 13,000 vertebral body
      augmentation procedures for nonpathological fractures performed in 2007 with a
      total national bill of 450 million US dollars. CONCLUSIONS: An increasing trend
      of hospitalizations, surgical treatment, and charges associated with lumbar spine
      fractures was observed between 2003 and 2007 on a national level. This trend,
      however, does not appear to be as steep as that of surgical utilization in
      degenerative spine disease. Furthermore, the ratio of spinal fusions to
      hospitalizations for lumbar fractures appears to be stable, possibly indicating
      no significant changes in indications for surgical intervention over the time
      period studied.

PMID- 21740125
TI  - Primary holocord ganglioneuroblastoma: case report.
AB  - The authors present a case of extensive primary intramedullary spinal CNS
      ganglioneuroblastoma (GNB) in a 23-year-old man. Central nervous system GNB is a
      poorly differentiated neuroepithelial tumor composed of neuroblasts and
      differentiated ganglion cells, and these lesions are extremely uncommon. Most
      previously reported primary intraaxial neuroblastic tumors were described in the
      brain. There has been only one other report of primary spinal cord CNS GNB
      published to date; the clinical course and prognosis for primary spinal cord
      tumors of this type are unknown. Similar tumor types demonstrate poor prognoses. 
      This 23-year-old man presented after 9 months of progressive myelopathy.
      Admission MR imaging showed an intraaxial enhancing mass extending from C-3 to
      the conus medullaris, with a holocord appearance in several areas. Due to the
      tumor size, operative intervention was initially limited to biopsy sampling.
      Chemotherapy resulted in histological maturation, but initial tumor regression
      was temporary. The patient suffered progressive quadriparesis, and neuroimaging
      demonstrated slow enlargement of the tumor and an associated syrinx. Nineteen
      months after diagnosis, the tumor was excised to gross-total resection in a 2
      stage operation. One year following resection, the patient had no radiographic
      recurrence and was functional in a wheelchair with minimal paresis in the upper
      extremities. This case represents the most extensive example of primary spinal
      intramedullary CNS GNB reported to date. Holocord tumors present a significant
      challenge to the neurosurgeon, and resection bears substantial risk of morbidity.
      In spinal cord CNS GNB, chemotherapy followed by complete resection may be the
      most effective means of tumor control.

PMID- 21740126
TI  - Disc spaces, vertebral dimensions, and angle values at the lumbar region: a
      radioanatomical perspective in spines with L5-S1 transitions: clinical article.
AB  - OBJECT: Low-back pain (LBP) has been associated with lumbar spines of normal
      morphology as well as those with L5-S1 "transitional" vertebrae. It is hard to
      find literature that quantifies the overall morphological changes in lumbar
      spines as related to transitional states. The object of this study was to
      investigate lumbar spine changes resulting from the presence of these
      transitional states. METHODS: The author quantified dimensions and angles and
      statistically compared the morphology of lumbar spines with or without L5-S1
      transitions in the context of LBP. Anteroposterior and lateral radiographs were
      obtained from 50 patients suffering from LBP without transitional anomalies at
      the L5-S1 junction. These radiographs were compared with anteroposterior and
      lateral radiographs from patients suffering from LBP with L5-S1 transitional
      states involving accessory L5-S1 articulations, and with anteroposterior and
      lateral radiographs from patients with L5-S1 unilateral or bilateral fusions.
      Twelve linear dimensions from the anteroposterior views and 8 angles from the
      lateral radiographs were measured. RESULTS: The mean values of linear dimensions
      differed in 1) disc heights, 2) vertebral heights and widths, 3) pedicles and
      interpedicular distances, 4) angle values, and 5) overall configuration of the
      lumbar curvatures. CONCLUSIONS: The L5-S1 accessory articulations led to
      increased lordotic curves, L-5 vertebral heights, and pedicle and angular
      dimensions. The L5-S1 fusions were related to smaller disc heights at all spaces,
      short and wide L-5 pedicles, taller and less wide transverse processes, and
      overall straighter spines with the least measures for all lumbar angles.
      Dimensional differences provided in this study may help in placing
      instrumentation at the lumbar vertebrae and working on intervertebral disc
      replacements in spines with specific L5-S1 transitional anomalies.

PMID- 21740127
TI  - Surgical management of coccidioidomycosis of the spine: clinical article.
AB  - OBJECT: Coccidioides immitis is a dimorphous fungus endemic in the southwestern
      US and northern Mexico. While its primary presentation is pulmonary, it can have
      devastating neurological sequelae. METHODS: The authors provide a retrospective
      review with long-term follow-up between 1986 and 2008 at a single institution.
      RESULTS: The authors identified 27 patients between 13 and 81 years old (mean
      41.4 years) with spinal coccidioides who were treated surgically at the Barrow
      Neurological Institute between 1986 and 2008. There were 24 males (89%) and 3
      females (11%). Eleven patients (41%) had cervical spine involvement, 15 (56%) had
      thoracic involvement, 7 (26%) had lumbar involvement, and 2 (7%) had sacral
      involvement. All 27 patients presented with localized or radiating pain. Nine
      patients (33%) had myelopathic symptoms at presentation, 5 (19%) had
      radiculopathy, 4 (15%) had fever, and 12 (44%) had progressive kyphosis. The
      disease was most frequently seen among African American patients (14 patients
      [52%]), followed by Caucasians (5 patients [19%]), Asians (3 patients [11%]), and
      Hispanics (3 patients [11%]). Ten patients (37%) required multiple operations at
      the same level. Follow-up was available in 19 patients (70%) (mean 9.8 months,
      range 1-39 months). Sixteen (84%) of these 19 patients improved from their
      preoperative baseline states, 1 (5%) was stable on examination, 1 patient's
      condition (5%) deteriorated compared with the preoperative examination, and 1
      patient (5%) died in the postoperative period. CONCLUSIONS: Although spinal
      involvement of coccidioidomycosis is relatively uncommon, a high index of
      suspicion and aggressive therapy are warranted to prevent devastating
      neurological injury, and lifelong antifungal therapy is often warranted.

PMID- 21740128
TI  - Chronic cerebellar hemorrhage in spontaneous intracranial hypotension:
      association with ventral spinal cerebrospinal fluid leaks: clinical article.
AB  - OBJECT: Spontaneous intracranial hypotension is an important cause of new-onset
      daily persistent headache. Cerebellar hemorrhage has been identified as a
      possible feature of spontaneous intracranial hypotension. The authors reviewed
      the MR imaging studies from a group of patients with spontaneous intracranial
      hypotension to assess the presence of cerebellar hemorrhage. METHODS: Medical
      records and radiological images were reviewed in 262 cases involving patients
      with spontaneous intracranial hypotension who had undergone MR imaging of the
      brain as well as spinal imaging. RESULTS: Chronic cerebellar hemorrhages were
      found in 7 (2.7%) of the 262 patients with spontaneous intracranial hypotension.
      These hemorrhages were found in 7 (19.4%) of the 36 patients with a ventral
      spinal CSF leak and in none of the 226 patients who did not have such a CSF leak
      (p < 0.0001). The degree of hemosiderin deposits was variable, ranging from mild
      involvement of the cerebellar folia to widespread superficial siderosis. Only the
      1 patient with superficial siderosis had symptoms due to the hemorrhages. The
      time period between the onset of symptoms due to spontaneous intracranial
      hypotension and MR imaging examination was significantly longer in those patients
      with cerebellar hemorrhage than in those with a ventral spinal CSF leak and no
      evidence for cerebellar hemorrhage (mean 19.6 years vs 2.3 months, p < 0.0001).
      CONCLUSIONS: Chronic cerebellar hemorrhage should be included among the
      manifestations of spontaneous intracranial hypotension. The severity is variable,
      but the hemorrhage generally is asymptomatic. The underlying spinal CSF leak is
      ventral and mostly of long duration.

PMID- 21740129
TI  - Management and prognosis of symptomatic patients with intramedullary spinal cord
      cavernoma: clinical article.
AB  - OBJECT: The authors conducted a study to assess the clinical pattern,
      radiological features, therapeutic strategies, and long-term outcomes in patients
      with intramedullary spinal cord cavernomas (ISCCs) based on a large case series.
      METHODS: This retrospective study identified 96 patients (60 males, 36 females)
      surgically (81 cases) or conservatively (15 cases) treated for ISCCs between May
      1993 and November 2007. Each diagnosis was based on MR imaging and spinal
      angiography evidence. For all surgically treated patients, the diagnosis was
      verified pathologically. The neurological outcomes pre- and postoperatively, as
      well as long-term follow-up, were assessed using the Aminoff-Logue Disability
      Scale. RESULTS: The mean age at the onset of symptoms was 34.5 years (range 9-80
      years). Of the lesions, 68 (71%) were located in the thoracic spine, 25 (26%) in
      the cervical spine, and only 3 (3%) in the lumbar spine. The median symptom
      duration was 19.7 months. The clinical behavior of the lesion was a slow
      progression in 73 cases and an acute decline in 23 cases. Long-term follow-up
      data (mean 45.8 months, range 10-183 months) were available for 75 patients (64
      surgical cases and 11 conservative cases). In the surgical group, a complete
      resection was achieved in 60 patients, and incomplete resection was detected in 4
      patients after operation. At the end of the follow-up period in the operative
      group, 23 patients (36%) improved, 35 (55%) remained unchanged, and 6 (9%)
      worsened. In the nonoperative group, 5 patients improved, 6 patients remained
      unchanged, and none worsened. CONCLUSIONS: For differential diagnosis, spinal
      angiography was necessary in some cases. For most symptomatic lesions, complete
      microsurgical resection of the symptomatic ISCC is safe and prevents rebleeding
      and further neurological deterioration. However, in patients whose lesions were
      small and located ventrally in the spinal cord, one can also opt for a rigorous
      follow-up, considering the high surgical risk.

PMID- 21740130
TI  - Outcomes of fusion surgery for ossification of the posterior longitudinal
      ligament of the thoracic spine: a multicenter retrospective survey: clinical
      article.
AB  - OBJECT: The aim of this study was to evaluate the outcomes of fusion surgery in
      patients with ossification of the posterior longitudinal ligament in the thoracic
      spine (T-OPLL) and to identify factors significantly related to surgical
      outcomes. METHODS: The study included 76 patients (34 men and 42 women with a
      mean age of 56.3 years) who underwent fusion surgery for T-OPLL at 7 spine
      centers during the 5-year period from 2003 to 2007. The authors evaluated the
      patient demographic data, underlying disease, preoperative comorbidities, history
      of spinal surgery, radiological findings, surgical methods, surgical outcomes,
      and complications. Surgical outcomes were assessed using the Japanese Orthopaedic
      Association (JOA) scale score for thoracic myelopathy (11 points) and the
      recovery rate. RESULTS: The mean JOA scale score was 4.6 +/- 2.1 points
      preoperatively and 7.7 +/- 2.5 points at the time of the final follow-up
      examination, yielding a mean recovery rate of 45.4% +/- 39.1%. The recovery rates
      by surgical method were 38.5% +/- 37.8% for posterior decompression and fusion,
      65.0% +/- 35.6% for anterior decompression and fusion via an anterior approach,
      28.8% +/- 41.2% for anterior decompression via a posterior approach, and 57.5% +/
      41.1% for circumferential decompression and fusion. The recovery rate was
      significantly higher in patients without diabetes mellitus (DM) than in those
      with DM. One or more complications were experienced by 31 patients (40.8%),
      including 20 patients with postoperative neurological deterioration, 7 with dural
      tears, 5 with epidural hematomas, 4 with respiratory complications, and 10 with
      other complications. CONCLUSIONS: The outcomes of fusion surgery for T-OPLL were
      favorable. The absence of DM correlated with better outcomes. However, a high
      rate of complications was associated with the fusion surgery.

PMID- 21740131
TI  - Anti-inflammatory treatments during the chronic phase of spinal cord injury
      improve locomotor function in adult mice.
AB  - Our previous data suggested that ongoing inflammation in the spinal cord 6 weeks
      following spinal cord injury was detrimental to locomotor function. Others have
      shown in the acute and sub-acute post-injury phase that microglial/macrophage
      activation and T regulatory cells are detrimental to recovery. Here, C57BL/6 mice
      with a moderately severe T9 contusion were injected intravenously daily with
      minocycline, which reduces microglial/macrophage activation, or with CD25
      antibodies, which reduce T regulatory cell function, starting at 6 weeks after
      injury. Both anti-inflammatory drugs caused an improvement in hindlimb locomotor
      function over the 2-week treatment, as measured by the Basso Mouse Scale (BMS).
      The improvement was functionally important, with mice having problems with
      coordinated stepping (BMS ~6) before treatment to walking essentially normally
      (BMS >7) at the end of the treatment. The effects diminished within 1 week after
      termination of the treatments, suggesting an ongoing and dynamic inflammatory
      process. The area of white matter or the inflammatory markers CD68 for activated
      microglia/macrophages and CD45 for leukocytes were not different between the
      groups. These data suggest that inflammation during the chronic phase following
      spinal cord injury reduces conduction through the epicenter, possibly by release
      of cytokines, and is amenable to treatment for improved neurological function.

PMID- 21740132
TI  - Electrospun nanofibrillar surfaces promote neuronal differentiation and function
      from human embryonic stem cells.
AB  - In this study, the impact of randomly oriented electrospun polyamide nanofibrous
      architecture on neurogenic differentiation of human embryonic stem cells (hESCs)
      compared with the lack of nanofibrous features in vitro in a neural-inducing
      condition was examined. Flow cytometry analysis of hESC-derived neural ectoderm
      (NE) showed nanofibrous surfaces capable of supporting NE by expression of higher
      percentages of related markers NESTIN, SOX1, and PAX6 in addition to
      significantly greater total cell proliferation as shown by Ki67 in the neurogenic
      condition. After replating hESC-derived NE, the differentiated cells expressed
      higher neuronal markers (TUJ1 and MAP2) and motor neuron markers (HB9, ISL1, and
      ChAT) at both the protein and mRNA levels on nanofibers. The presence of
      developed spread neurites and plausible neurite connections were shown by
      scanning electron microscopy. Additionally, Na(+) and Ca(2+) currents in
      differentiated neurons on nanofibers were significantly greater than both control
      and generated action potentials. Moreover, less duration of inward currents,
      greater negative resting membrane potential, and enhanced expression and
      functionality of ionic channel genes were observed in neuronal cells on
      nanofibers. These results indicated that a nanofibrillar surface along with
      neurogenic growth factors provided a better environment for hESC neurogenic
      differentiation and function, which holds great promise in prospective tissue
      engineering applications.

PMID- 21740133
TI  - Mild traumatic brain injury and diffuse axonal injury in swine.
AB  - Until recently, mild traumatic brain injury (mTBI) or "concussion" was generally
      ignored as a major health issue. However, emerging evidence suggests that this
      injury is by no means mild, considering it induces persisting neurocognitive
      dysfunction in many individuals. Although little is known about the
      pathophysiological aspects of mTBI, there is growing opinion that diffuse axonal
      injury (DAI) may play a key role. To explore this possibility, we adapted a model
      of head rotational acceleration in swine to produce mTBI by scaling the
      mechanical loading conditions based on available biomechanical data on concussion
      thresholds in humans. Using these input parameters, head rotational acceleration
      was induced in either the axial plane (transverse to the brainstem; n=3), causing
      a 10- to 35-min loss of consciousness, or coronal plane (circumferential to the
      brainstem; n=2), which did not produce a sustained loss of consciousness. Seven
      days following injury, immunohistochemical analyses of the brains revealed that
      both planes of head rotation induced extensive axonal pathology throughout the
      white matter, characterized as swollen axonal bulbs or varicosities that were
      immunoreactive for accumulating neurofilament protein. However, the distribution
      of the axonal pathology was different between planes of head rotation. In
      particular, more swollen axonal profiles were observed in the brainstems of
      animals injured in the axial plane, suggesting an anatomic substrate for
      prolonged loss of consciousness in mTBI. Overall, these data support DAI as an
      important pathological feature of mTBI, and demonstrate that surprisingly overt
      axonal pathology may be present, even in cases without a sustained loss of
      consciousness.

PMID- 21740134
TI  - Is there a role for fasciotomy in Crotalinae envenomations in North America?
AB  - CONTEXT: The local effects of Crotalinae envenomation can cause significant
      tissue destruction, pain, paresthesias, and deformity of the limb, which mimic
      findings of compartment syndrome, despite rare subfascial penetration of the
      fangs. Complicating this are the various techniques and ideas about what
      determines compartment syndrome combined with the fact that elevated
      intracompartmental pressures have been documented after Crotalinae envenomation,
      without clear evidence of compartment syndrome or tissue hypoperfusion.
      OBJECTIVE: The purpose of this review is to evaluate the North American
      literature to provide an evidenced-based conclusion about the indications for
      fasciotomy in Crotalinae envenomations. METHODS: The search was conducted with
      studies published only in the English language. The search included all human and
      animal publications, regardless of the format of study. The Cochrane Central
      Register, MEDLINE/ Pub Med, Scopus, and Biological Science databases were
      searched. Citations from all the articles were also cross-referenced if they were
      pertinent to the review. Major toxicology and emergency medicine and surgical
      textbooks were also referenced. Abstracts from the North American Congress of
      Clinical Toxicology, Poisonidex(r), and personal articles were also scanned to
      complete the process, resulting in a total of 640 sources. Papers were excluded
      if they were duplicates, non-North American, involved excisional therapy, or did
      not discuss fasciotomy. This left 99 publications applicable to our study.
      FINDINGS: No randomized controlled trials, 8 animal experiments, 1 human
      prospective observational study, 24 retrospective reviews, 32 review articles, 10
      case reports, 15 textbooks references, 2 abstracts, and 7 editorials were
      included in the analysis. Controlled animal experiments show that crotaline Fab
      antivenin reduces intracompartmental pressure and increases tissue perfusion,
      while fasciotomy either has no beneficial effect or worsens myonecrosis. The case
      reports and opinions supporting fasciotomy come from the surgical literature and
      precede the modern crotaline Fab antivenin. CONCLUSION: The current evidence does
      not support the use of fasciotomy or dermotomy following Crotalinae envenomation
      with elevated intracompartmental pressures. At present, early and adequate
      administration of crotaline Fab antivenin is the treatment of choice. Fasciotomy
      cannot be recommended until further well-designed investigations are completed.

PMID- 21740135
TI  - The combination of cobinamide and sulfanegen is highly effective in mouse models
      of cyanide poisoning.
AB  - CONTEXT: Cyanide is a component of smoke in residential and industrial fires, and
      accidental exposure to cyanide occurs in a variety of industries. Moreover,
      cyanide has the potential to be used by terrorists, particularly in a closed
      space such as an airport or train station. Current therapies for cyanide
      poisoning must be given by intravenous administration, limiting their use in
      treating mass casualties. OBJECTIVE: We are developing two new cyanide antidotes-
      cobinamide, a vitamin B(12) analog, and sulfanegen, a 3-mercaptopyruvate prodrug.
      Both drugs can be given by intramuscular administration, and therefore could be
      used to treat a large number of people quickly. We now asked if the two drugs
      would have an augmented effect when combined. MATERIALS AND METHODS: We used a
      non-lethal and two different lethal models of cyanide poisoning in mice. The non
      lethal model assesses neurologic recovery by quantitatively evaluating the innate
      righting reflex time of a mouse. The two lethal models are a cyanide injection
      and a cyanide inhalation model. RESULTS: We found that the two drugs are at least
      additive when used together in both the non-lethal and lethal models: at doses
      where all animals died with either drug alone, the combination yielded 80 and 40%
      survival in the injection and inhalation models, respectively. Similarly, drug
      doses that yielded 40% survival with either drug alone, yielded 80 and 100%
      survival in the injection and inhalation models, respectively. As part of the
      inhalation model, we developed a new paradigm in which animals are exposed to
      cyanide gas, injected intramuscularly with an antidote, and then re-exposed to
      cyanide gas. This simulates cyanide exposure of a large number of people in a
      closed space, because people would remain exposed to cyanide, even after
      receiving an antidote. CONCLUSION: The combination of cobinamide and sulfanegen
      shows great promise as a new approach to treating cyanide poisoning.

PMID- 21740136
TI  - Can death unrelated to secondary causes be predicted in intubated comatose
      tricyclic antidepressant-poisoned patients?
AB  - CONTEXT: It has been stated that the level of consciousness at presentation is
      the most sensitive clinical predictor of dysrhythmia and seizure in patients with
      tricyclic antidepressant (TCA) overdose. OBJECTIVE: To assess the prognostic
      value of the clinical characteristics and electrocardiographic (ECG) parameters
      in intubated comatose TCA-poisoned patients for predicting death. MATERIALS AND
      METHODS: In this retrospective, unmatched case-control study--conducted in
      Loghman-Hakim Poison Hospital in Tehran, Iran, between March 2005 and September
      2010--the medical charts of 25 non-survived (cases) and 72 survived (controls)
      TCA-poisoned patients, initially presenting with deep coma (GCS <= 8) and being
      intubated before or after hospital presentation, were evaluated. Exclusion
      criteria were multiple drug ingestion, head trauma, underlying heart diseases,
      history of previous convulsive disorders, and late death. Age, gender, specific
      TCA ingested, manner of poisoning, time between ingestion and presentation,
      occurrence of seizure, and the patient's initial emergency department vital signs
      were extracted and recorded. The first 12-lead ECG performed after hospital
      presentation was evaluated. RESULTS: Ten cases and none of the controls had
      advanced ECG changes (ventricular fibrillation, torsades des pointes, or
      asystole). Using a logistic regression model, from variables with a statistically
      significant difference between the two groups (i.e. ingestion of nortriptyline
      and amitriptyline, pulse and respiratory rates at presentation, occurrence of
      seizure [before and after presentation or both], height of R wave in lead aVR,
      T40-ms frontal plane QRS axis, and occurrence of premature ventricular
      contraction), only seizure after hospital presentation reached significance
      regarding prediction of death (OR = 40.88; 95% CI = 9.93-168.39; p < 0.001).
      CONCLUSION: Neither ECG parameters nor clinical characteristics of the intubated
      comatose patients with TCA toxicity predicts death in patients who had not died
      due to the secondary causes. The only prognostic indicator of death in such
      patients is seizure after hospital presentation.

PMID- 21740137
TI  - Management of intentional superwarfarin poisoning with long-term vitamin K and
      brodifacoum levels.
AB  - CONTEXT: Brodifacoum is a widely available superwarfarin used as a commercial
      rodenticide. Toxicity from long-acting anticoagulant rodenticides, primarily from
      uncontrolled bleeding, has been reported. Very little published toxicokinetic
      data are available for human brodifacoum poisoning. Management is also
      contentious with uncertainty over the dose, frequency, and duration of antidote
      treatment with vitamin K. The role of brodifacoum levels in guiding management is
      not entirely established. METHODS: A novel, highly sensitive method was developed
      for measuring all commercially available rodenticide-hydroxycoumarin anti
      coagulants. Monthly brodifacoum levels were performed in two patients to
      determine half-life and expected time for levels to fall below 10 MUg/L. RESULTS:
      We report two concurrent cases at our clinical toxicology service that required
      prolonged treatment with oral vitamin K to achieve normalisation of coagulation
      studies. Brodifacoum elimination appears to follow first-order kinetics. Case 1
      had a brodifacoum elimination half-life of 33 days and was treated with vitamin K
      (100 mg) for 6 months. Case 2 was treated with vitamin K (100 mg) for 3 months
      with a half-life of 15 days. DISCUSSION: Our cases illustrate the positive
      experience in the utility of brodifacoum levels to confirm diagnosis and aid in
      directing antidote therapy. Large ingestions of brodifacoum-containing
      rodenticides are likely to require high-dose oral vitamin K administered daily. A
      brodifacoum level below 10 MUg/L was associated with a normal coagulation profile
      following completion of vitamin K(1) therapy in our cases; this level may prove
      to be a safe treatment cessation threshold.

PMID- 21740138
TI  - Medication errors associated with the use of ethanol and fomepizole as antidotes
      for methanol and ethylene glycol poisoning.
AB  - INTRODUCTION: Little is known about medication errors which occur with the
      antidotes ethanol and fomepizole, used for treatment of methanol and ethylene
      glycol poisoning. Study objectives were to describe and compare the frequency,
      type, outcome and underlying causes of medication errors associated with ethanol
      and fomepizole. METHODS: Patients aged >=13 years were included if they were
      hospitalized in 1996-2005 for methanol or ethylene glycol poisoning and treated
      with ethanol or fomepizole. Charts from 10 hospitals were separately reviewed by
      two abstracters who recorded case details. A consensus panel of clinicians used
      the abstracted data to identify medication errors and classify error outcome.
      Fisher's exact test determined significant differences in the proportion of
      ethanol and fomepizole-treated cases with medication error and univariate
      logistic regression identified risk factors associated with harmful dosage
      errors. RESULTS: There were 145 ethanol- and 44 fomepizole-treated cases. There
      was >=1 medication error in 113/145 (78%) ethanol- and 20/44 (45%) fomepizole
      treated cases (p = 0.0001) with more ethanol-related errors involving excessive
      dose, inadequate monitoring and inappropriate antidote duration. Harmful errors
      occurred in 19% of ethanol- and 7% of fomepizole-treated cases (p = 0.06) and
      were largely due to excessive antidote dose or delayed antidote initiation.
      Occurrence of harmful dosage error was reduced in cases with Poison Control
      Centre consultation, odds ratio (95% confidence interval) 0.39 (0.17, 0.91),
      hemodialysis 0.37 (0.16, 0.88), or fomepizole versus ethanol 0.24 (0.06, 1.04).
      CONCLUSION: Fomepizole was less prone to medication error than ethanol. Error
      related harm was most commonly due to excessive antidote dose or delayed antidote
      initiation.

PMID- 21740139
TI  - Monitoring trends in dextromethorphan abuse using the National Poison Data
      System: 2000-2010.
AB  - CONTEXT: Dextromethorphan (DXM) abuse persists among US youth and should be
      closely monitored because of the risks of severe medical complications,
      addiction, and psychiatric sequelae. Prior investigations have demonstrated DXM
      to be an emerging drug of abuse with increasing national prevalence through 2004.
      OBJECTIVE: To extend existing substance abuse survey results by describing
      demographic, geographic, product, and outcome trends in medically significant DXM
      abuse cases (those reported to US poison centers). METHODS: National Poison Data
      System (NPDS) data are collected and compiled in real time by all 57 US poison
      centers. Demographic, geographic, product, and outcome data for all intentional
      DXM abuse cases reported to the NPDS between 2000 and 2010 were analyzed.
      RESULTS: A total of 44,206 DXM abuse cases met inclusion criteria, 34,755 of
      which were single-substance exposures. The mean annual prevalence of DXM cases
      reported to poison control centers was 13.4 cases per million population for all
      ages and 113.0 cases per million for 15-19 year olds. The prevalence of DXM cases
      for all ages increased steadily (p = 0.002, Cochran-Armitage trend test) until
      2006 to a peak of 17.6 calls/million and has subsequently plateaued at 15.7 cases
      per million in 2010. This trend is also seen in the most commonly abused brand of
      DXM products, Coricidin((r)). A preponderance of male adolescents was noted
      throughout the study period. The odds of a severe outcome are increased for a
      multi-substance exposure (OR: 2.53; 95% CI: 2.14-2.99, logistic regression); odds
      were not significantly increased for any of the most commonly abused product
      brands. CONCLUSION: The increasing trend of DXM abuse cases noted in the first
      half of the decade by previous studies seems to have peaked at 17.6 calls per
      million population in 2006. It is likely that a combination of legislative,
      educational, and economic initiatives are responsible for the observed plateau.

PMID- 21740140
TI  - Metam sodium intoxication: the specific role of degradation products--methyl
      isothiocyanate and carbon disulphide--as a function of exposure.
AB  - Introduction. The objective was to evaluate the toxicity of poisoning by metam
      sodium, a dithiocarbamate fumigant, the breakdown products of which are methyl
      isothiocyanate (MITC), carbon disulphide (CS2), and dihydrogen sulphide (H2S).
      Methods. This is a retrospective, observational case series of metam sodium
      exposure cases reported to the Angers Poison and Toxicovigilance Centre from 1992
      through 2009. Results. A total of 106 cases of metam sodium exposure were
      recorded and 102 cases were included in this study. All cases of exposure were
      unintentional. Occupational poisoning occurred in eight cases. The most common
      route of exposure was inhalation (n = 96). In 79 cases, the patients were people
      living near fields where metam sodium had recently been applied. Most of the
      reported symptoms involved irritation of the eyes (n = 76), throat and nose (n =
      65), attributable to MITC. Cough and dyspnoea occurred in four cases but no
      persistent, irritant-induced asthma or persistent exacerbation of asthma was
      observed. Sixteen patients at two different sites of pollution were exposed to
      emanations from the drainage system in their homes following the illicit
      discharge of metam sodium into the sewers. Most presented with nausea and
      headaches, but only four experienced eye or throat irritation. A breakdown
      product other than MITC was involved: air analysis at one site revealed the
      presence of CS2 (337 mg/m(3)) and no H2S. Two of these patients, who had consumed
      some alcohol, experienced dysgeusia but no disulfiram-like reaction. The only
      lethal case recorded was a truck driver who was found dead of acute lung injury
      after falling into a tank that had previously contained metam sodium. Two
      patients who ingested a dilute solution, presented with mild epigastric pain.
      Four skin exposures caused erythema (n = 2), moderate burns (n = 1), and
      urticaria (n = 1). According to the poisoning severity score, their symptoms were
      minor in 99% of cases. Conclusion. Acute metam sodium exposure usually causes
      minor symptoms. They vary as a function of the circumstances of exposure, which
      determine the degradation product that forms. On contact with moist soil, metam
      sodium decomposes into MITC and causes irritant symptoms. Under specific
      conditions, such as a spillage in the drainage system, metam sodium can degrade
      into CS2 and cause neurological signs.

PMID- 21740141
TI  - Massive acetylcysteine overdose associated with cerebral edema and seizures.
AB  - CONTEXT: Acetylcysteine is a safe and effective treatment for the prevention of
      hepatic injury due to acetaminophen poisoning. While dosing errors are common, in
      most cases, overdoses produce minimal clinical effects. CASE REPORT: We describe
      a patient who received 150 g of IV acetylcysteine over 32 h when the clinician
      ordered the infusion doses be administered as an hourly dose (100 mg/kg/h) rather
      than administered over the infusion duration (100 mg/kg over 16 h). After
      approximately 28 h of receiving 100 mg/kg/h, the patient developed delirium, and
      seizures that progressed to cerebral edema, uncal herniation, and ultimately
      severe brain injury. No other cause for her symptoms was identified during an
      extensive workup. DISCUSSION: This case suggests that massive IV acetylcysteine
      overdose can cause cerebral dysfunction and life-threatening effects.

PMID- 21740142
TI  - Severe propranolol and ethanol overdose with wide complex tachycardia treated
      with intravenous lipid emulsion: a case report.
AB  - BACKGROUND: Propranolol is a highly lipid-soluble beta-blocker. We describe a
      case of severe propranolol overdose, with atypical dysrhythmia--wide complex
      tachycardia--which was successfully treated with lipid emulsion. CASE REPORT: A
      31-year-old woman ingested approximately 3.6 g of propranolol along with ethanol.
      Clinical manifestations of poisoning included coma, seizures, respiratory
      failure, hypoglycaemia, circulatory shock, and dysrhythmias. An ECG revealed
      nonspecific intraventricular conduction delay, followed by wide complex
      supraventricular tachycardia. Toxicological analysis of blood showed ethanol 2.42
      g/L and propranolol 4.21 mg/L. The patient responded poorly to conventional
      therapy, so intravenous lipid emulsion was used. Apart from IV dopamine, the only
      treatment after the onset of wide complex tachycardia was 20% Intralipid.
      Transient improvement was noticed after the initial dose of 500 mL; during the
      infusion of further Intralipid, blood pressure returned to normal and sinus
      rhythm was re-established. CONCLUSION: We believe that lipid emulsion had a
      beneficial effect in the treatment of propranolol toxicity.

PMID- 21740143
TI  - Three cases of "spice" exposure.
AB  - INTRODUCTION: We describe three cases with confirmed exposure to "spice" by
      detection of the metabolites JWH-018 and/or JWH-073 in urine. All cases had a
      negative urine drug screen. Case 1. A 25-year-old male with possible seizure,
      tachycardia, acidosis, and unresponsiveness, presented to a local emergency
      department (ED) after smoking a "spice" product. His symptoms resolved with
      benzodiazepines, fluid, and observation. His urine tested positive for JWH-018
      and negative for JWH-073 metabolites. Case 2. A 21-year-old male was found
      unresponsive after smoking "spice." He had hypertension, was agitated, and had a
      Glasgow Coma Score of 7; the patient was intubated. The skin was warm and dry.
      His symptoms resolved with IV fluids and he was discharged home after 24 h. His
      urine tested positive for metabolites of JWH-018 and JWH-073. Case 3. A 19-year
      old male was brought to the ED 1 h after smoking a "spice" product and having
      paranoia and delusions. His urine tested positive for JWH-018 and JWH-073
      metabolites. He was discharged asymptomatic after observation for a few hours.
      DISCUSSION: Spice products are new and abused for their psychogenic effects and
      mood alteration. These cases exhibited changes consistent with either an
      anticholinergic or sympathomimetic agent that resolved following general
      supportive care.

PMID- 21740144
TI  - Serum concentrations in three children with unintentional tetrahydrozoline
      overdose.
AB  - BACKGROUND: Major symptoms can occur from tetrahydrozoline (THZ) overdoses in
      young children, requiring intensive care management. We report three cases that
      presented with CNS depression and cardiovascular effects where serum
      concentrations were performed. CASE REPORT: Case 1 ingested an unknown amount of
      eye drops containing THZ, resulting in altered mental status, bradycardia,
      hypothermia, and hypotension. Cases 2 and 3 ingested 7.5 mL of eye drops
      containing THZ. Case 2 presented to the emergency department (ED) without
      symptoms but became lethargic and bradycardic 90 min after ingestion. By
      contrast, Case 3 became lethargic 15 min after ingestion and required intubation
      on arrival to the ED. All children were admitted to ICU for observation and
      improved within 24 h of ingestion. Urine obtained for drug screening was positive
      for THZ. Blood was obtained to assess level using gas-chromatography mass
      spectrometry (GC-MS). CASE DISCUSSION: Case 1 had plasma levels of 51.4 and 23.6
      ng/mL at 7 and 12 h, respectively, after ingestion, revealing a half-life of 4.4
      h. Numerous case reports have been published documenting the dangers of ingesting
      these topical over-the-counter (OTC) products. However, human PK data are not
      available to help in our understanding of THZ toxicokinetics and disposition in
      humans after ingestion. CONCLUSION: We report three pediatric cases after
      ingestion of THZ where plasma concentrations were obtained with a calculated half
      life of 4.4 h in one case.

PMID- 21740145
TI  - Chemical burn caused by dermal injection of potassium chloride.
AB  - This report contains images and a summary of a 31-year-old male patient who
      presented with skin lesions after subcutaneous injection of potassium chloride in
      an attempted suicide. Both forearms showed formation of vesicles with purple
      necrotic changes. Escharotomy, debridement, artificial skin graft, and local flap
      surgery were performed during hospitalization. This report includes images
      illustrating the course of the chemical burn due to subcutaneous injection of
      potassium chloride, and a brief review.

PMID- 21740146
TI  - Atrial fibrillation induced by mad honey intoxication in a patient with Wolf
      Parkinson-White syndrome.

PMID- 21740147
TI  - Atrial fibrillation due to olanzapine overdose.

PMID- 21740148
TI  - Sympathomimetic toxicity in a case of analytically confirmed recreational use of
      naphyrone (naphthylpyrovalerone).
AB  - CONTEXT: Naphyrone (naphthylpyrovalerone) is a cathinone derivative and
      recreational drug related to mephedrone. CASE: We report a 31-year-old man who
      ingested a dose of naphyrone (100 mg), which produced acute sympathomimetic
      toxicity with restlessness, insomnia, anxiety, and hallucinations lasting for 2
      days. Naphyrone was detected in the patient's plasma by gas chromatography with
      mass spectrometry at concentrations of 0.03 and 0.02 mg/L, 40 and 60 h after drug
      intake, respectively. DISCUSSION: Based on the present case report and user web
      reports, as well as on the chemical structure and pharmacological
      characteristics, naphyrone produces stimulant-like psychotropic effects and
      sympathomimetic toxicity.

PMID- 21740149
TI  - Unrecognized fatalities related to colchicine in hospitalized patients.
AB  - BACKGROUND: Colchicine is commonly used for the treatment of gout and
      occasionally for other inflammatory diseases. It has a narrow therapeutic index
      and the potential for severe or fatal toxicity. OBJECTIVES: We sought to
      determine (1) the frequency of colchicine toxicity among hospitalized patients
      taking colchicine who died during an admission, (2) the likelihood that
      colchicine contributed to death, (3) whether patients were taking interacting
      medications that could have contributed to toxicity, and (4) whether colchicine
      dosing among these patients adhered to established guidelines. METHODS: We
      conducted an IRB-approved, retrospective chart review at an urban, tertiary care,
      1228-bed, university hospital. Subjects included hospitalized patients who
      received colchicine and died in hospital between 1 January 2000 and 28 February
      2007. We reviewed charts for signs and symptoms of colchicine toxicity. An expert
      panel reviewed each case and classified the likelihood of colchicine toxicity,
      the likelihood of a causal role of colchicine in the death using the WHO
      classification system, and the appropriateness of colchicine dosing. RESULTS:
      Thirty-seven hospitalized patients who died during the 86-month study period
      received colchicine. Toxicity was unlikely in 20/37, possible in 8/37, likely in
      5/37, and certain in 4/37. A contributing role for colchicine in causing death
      was unlikely in 24/37, possible in 7/37, likely in 3/37, and certain in 3/37.
      Colchicine doses (based on creatinine clearance) exceeded the accepted range for
      12 patients, including 10 of 17 cases of toxicity and 8 of 13 cases of death
      classified as possible or higher. Seventeen patients received interacting
      medications, including 8 of 17 cases of toxicity and 8 of 13 cases of death
      classified as possible or higher. CONCLUSION: Colchicine toxicity was frequent in
      this cohort and may have contributed to about one-third of the deaths.
      Inappropriate dosing of colchicine occurred frequently and was related to
      toxicity and death.

PMID- 21740150
TI  - Understanding microbialite morphology using a comprehensive suite of three
      dimensional analysis tools.
AB  - Microbialites can have complex morphologies that preserve clues to ancient
      microbial ecology. However, extracting and interpreting these clues is
      challenging due to both the complexity of microbial structures and the
      difficulties of connecting morphology to microbial processes. Fenestrate
      microbialites from the 2521+/-3 Ma Gamohaan Formation, South Africa, have
      intricate structures composed of three distinct microbial structures: steeply
      dipping supports (surfaces defined by organic inclusions), more shallowly dipping
      supports with diffuse organic inclusions below them, and draping laminae. In
      polished slabs, shallowly dipping supports with diffuse organic inclusions show
      apparent dips from 27 degrees  to 60 degrees , and supports without associated
      zones of diffuse inclusions dip 75 degrees  to 88 degrees , which suggests a
      distinction between support types based on orientation. However, dips exposed in
      polished slabs are apparent dips, and three-dimensional analysis is required for
      analysis of true dips. Through the Keck Center for Active Visualization in Earth
      Sciences (KeckCAVES), we used locally developed software that controls a three
      dimensional environment with head and hand tracking (an "immersive environment")
      to visualize and interpret virtual microbialite data sets. Immersive environments
      have not penetrated into standard scientific work processes ("workflows") due to
      their high costs, steep learning curves, and low productivity for users. By
      contrast, our suite of software tools allowed us to develop a personalized
      scientific workflow that provides a complete path from initial ideas to
      characterization of fenestrate microbialites' features. Results of three
      dimensional analysis of fenestrate microbialites show that supports with
      inclusions dip 65 degrees  to 75 degrees , whereas supports without inclusions
      dip 85 degrees  to 90 degrees . These results demonstrate that all supports have
      very steep dips, and a 10 degrees  dip gap exists between supports with and
      without inclusions, which suggests they grew in fundamentally different ways.
      Results also emphasize how valuable three-dimensional analysis is when combined
      with a comprehensive workflow for understanding intricate structures such as
      fenestrate microbialites.

PMID- 21740151
TI  - Interview with Rohina Rubicz, winner of the 2010 Gabriel W. Lasker prize.

PMID- 21740152
TI  - Gender differences in ancestral contribution and admixture in Venezuelan
      populations.
AB  - The origin of the contribution of uniparental heritage were analyzed in 615
      samples of individuals proceeding from 13 towns classified according to historic
      differences in their emergence and development as African-derived, European
      derived, and admixed/urban. Mitochondrial and Y-chromosome haplogroups were
      identified by PCR-restriction fragment length polymorphism. The results were
      compared with previous estimates of admixture made with autosomal markers and
      with historic aspects. The results show a predominantly indigenous genetic
      contribution through the female, being more prevalent in urban populations; the
      African contribution, although dispersed, presents a larger concentration in the
      African-derived towns, whereas the European contribution is limited to
      populations with this origin, reflecting isolation and the conservation of the
      distribution pattern of genes of the Colonial era. With regard to admixture
      through males, it is almost exclusively of European origin, whereas the African
      contribution is basically concentrated in the African-derived towns, and the
      Amerindian lineages are almost nonexistent. The genome of paternal heredity, as
      opposed to the autosomal and the mitochondrial, shows a homogeneous pattern of
      admixture that is independent of the origin of the population studied, suggesting
      that European genes have been introduced into the Venezuelan population through
      male immigrations, whereas the indigenous contribution has been preserved in the
      Venezuelan genetic pool through the women. These results provide evidence of the
      heterogeneity in the genetic origin of the Venezuelan population, which should be
      taken into account in forensic and epidemiologic genetic studies.

PMID- 21740153
TI  - Selection on the human bitter taste gene, TAS2R16, in Eurasian populations.
AB  - Bitter taste is one of the most important senses alerting humans to noxious
      foods. In gatherer communities, sensitivity to bitterness is presumably
      advantageous because of various noxious plants. TAS2R16 is the gene coding the
      taste receptor molecules for some of the most common toxins in plants. A previous
      study of this gene indicated selection has increased the frequency of a derived
      allele in this gene that arose before the human expansion out of Africa. We have
      applied a different methodology for detecting selection, the Long Range Haplotype
      (LRH) analysis, to TAS2R16 in a larger sampling of populations from around the
      world. The haplotype with the derived alleles at both the functional polymorphism
      and a polymorphism in the regulatory region of TAS2R16 showed evidence for recent
      positive selection in most of the Eurasian populations, though the highest
      selection signal occurs in Mbuti Pygmies, an African hunter-gatherer group. In
      Eurasia, only populations of Mesopotamia and the southeast coast of China have no
      signals of selection. The evidence of recent selection found in most Eurasian
      populations differs from the geographic pattern seen in the earlier study of
      selection. One can speculate that the difference may result from a gathering
      lifestyle extending into the most recent 10,000 yrs and the need to recognize
      newly encountered bitter natural toxins as populations expanded into new
      environments and the biota changes with the ending of the most recent ice age.
      Alternatively, the promoter region variant may be a marker for altered function
      beyond what the derived amino acid allele conferred.

PMID- 21740154
TI  - Lactase persistence in central Asia: phenotype, genotype, and evolution.
AB  - The aim of the present study is to document the evolution of the lactase
      persistence trait in Central Asia, a geographical area that is thought to have
      been a region of long-term pastoralism. Several ethnic groups co-exist in this
      area: Indo-Iranian speakers who are traditionally agriculturist (Tajik) and
      Turkic speakers who used to be nomadic herders (Kazakh, Karakalpak, Kyrgyz,
      Turkmen). It was recently demonstrated that horse milking practice existed in the
      Botai culture of Kazakhstan as early as 5,500 BP ( Outram et al. 2009 ). However,
      the frequency of the lactase persistence trait and its genetic basis in Central
      Asian populations remain largely unknown. We propose here the first genotype
      phenotype study of lactase persistence in Central Asia based on 183 individuals,
      as well as the estimation of the time of expansion of the lactase-persistence
      associated polymorphism. Our results show a remarkable genetic-phenotypic
      correlation, with the causal polymorphism being the same than in Europe (
      13.910C>T, rs4988235). The lactase persistence trait is at low frequency in these
      populations: between 25% and 32% in the Kazakh population (traditionally
      herders), according to phenotype used, and between 11% and 30% in the Tajiko
      Uzbek population (agriculturalists). The difference in lactase persistence
      between populations, even if small, is significant when using individuals
      concordant for both excretion of breath hydrogen and the lactose tolerance blood
      glucose test phenotypes (P = 0.018, 25% for Kazakh vs. 11% for Tajiko-Uzbeks),
      and the difference in frequency of the -13.910*T allele is almost significant (P
      = 0.06, 30% for Kazakhs vs. 19% for Tajiko-Uzbeks). Using the surrounding
      haplotype, we estimate a date of expansion of the T allele around 6,000-12,000
      yrs ago, which is consistent with archaeological records for the emergence of
      agropastoralism and pastoralism in Central Asia.

PMID- 21740155
TI  - The border effect in surname structure: an Italian-Slovenian case study.
AB  - Population surname structure in northeastern Italy municipalities, in which small
      Slovenian-speaking groups are present, are compared with neighboring populations
      of both Italian and Slovenian nationality. In the early 20th century those
      municipalities were part of the Italian territory and underwent a massive
      Italianization process that led to the mutation of the original Slovenian
      surnames into a derived Italian form. In order to track surname relationships
      among the examined communities, two different similarity analyses were performed:
      the first using the surnames as they are recorded in the Italian and Slovenian
      official telephone directories, and the second restoring the Italianized
      Slovenian surnames to their original form and then recalculating the populations'
      similarity. Both comparisons evidence a separation that depends on nationality,
      which is less marked after restoring surnames to their original form.
      Geographical elements, older historical events, and socioeconomic traits allow
      interpretation of these results.

PMID- 21740156
TI  - The Austroasiatic Munda population from India and Its enigmatic origin: a HLA
      diversity study.
AB  - The Austroasiatic linguistic family disputes its origin between two
      geographically distant regions of Asia, India, and Southeast Asia, respectively.
      As genetic studies based on classical and gender-specific genetic markers
      provided contradictory results to this debate thus far, we investigated the HLA
      diversity (HLA-A, -B, and -DRB1 loci) of an Austroasiatic Munda population from
      Northeast India and its relationships with other populations from India and
      Southeast Asia. Because molecular methods currently used to test HLA markers
      often provide ambiguous results due to the high complexity of this polymorphism,
      we applied two different techniques (reverse PCR-SSO typing on microbeads arrays
      based on Luminex technology, and PCR-SSP typing) to type the samples. After
      validating the resulting frequency distributions through the original statistical
      method described in our companion article ( Nunes et al. 2011 ), we compared the
      HLA genetic profile of the sampled Munda to those of other Asiatic populations,
      among which Dravidian and Indo-European-speakers from India and populations from
      East and Southeast Asia speaking languages belonging to different linguistic
      families. We showed that the Munda from Northeast India exhibit a peculiar
      genetic profile with a reduced level of HLA diversity compared to surrounding
      Indian populations. They also exhibit less diversity than Southeast Asian
      populations except at locus DRB1. Several analyses using genetic distances
      indicate that the Munda are much more closely related to populations from the
      Indian subcontinent than to Southeast Asian populations speaking languages of the
      same Austroasiatic linguistic family. On the other hand, they do not share a
      closer relationship with Dravidians compared with Indo-Europeans, thus arguing
      against the idea that the Munda share a common and ancient Indian origin with
      Dravidians. Our results do not favor either a scenario where the Munda would be
      representative of an ancestral Austroasiatic population giving rise to an
      eastward Austroasiatic expansion to Southeast Asia. Rather, their peculiar
      genetic profile is better explained by a decrease in genetic diversity through
      genetic drift from an ancestral population having a genetic profile similar to
      present-day Austroasiatic populations from Southeast Asia (thus suggesting a
      possible southeastern origin), followed by intensive gene flow with neighboring
      Indian populations. This conclusion is in agreement with archaeological and
      linguistic information. The history of the Austroasiatic family represents a
      fascinating example where complex interactions among culturally distinct human
      populations occurred in the past.

PMID- 21740157
TI  - Allele frequency estimation from ambiguous data: using resampling schema in
      validating frequency estimates and in selective neutrality testing.
AB  - The development of molecular typing techniques applied to the study of population
      genetic diversity originates data with increasing precision but at the cost of
      some ambiguities. As distinct techniques may produce distinct kinds of
      ambiguities, a crucial issue is to assess the differences between frequency
      distributions estimated from data produced by alternative techniques for the same
      sample. To that aim, we developed a resampling scheme that allows evaluating, by
      statistical means, the significance of the difference between two frequency
      distributions. The same approach is then shown to be applicable to test selective
      neutrality when only sample frequencies are known. The use of these original
      methods is presented here through an application to the genetic study of a Munda
      human population sample, where three different HLA loci were typed using two
      different molecular methods (reverse PCR-SSO typing on microbeads arrays based on
      Luminex technology and PCR-SSP typing), as described in details in the companion
      article by Riccio et al. [The Austroasiatic Munda population from India and its
      enigmatic origin: An HLA diversity study. Hum. Biol. 38:405-435 (2011)]. The
      differences between the frequency estimates of the two typing techniques were
      found to be smaller than those resulting from sampling. Overall, we show that
      using a resampling scheme in validating frequency estimates is effective when
      alternative frequency estimates are available. Moreover, resampling appears to be
      the unique way to test selective neutrality when only frequency data are
      available to describe the genetic structure of populations.

PMID- 21740158
TI  - Errata.

PMID- 21740159
TI  - Relaxin does not rescue coronal suture fusion in craniosynostotic rabbits.
AB  - OBJECTIVES: Craniosynostosis affects 1 in 2000 to 3000 live births and may result
      in craniofacial and neural growth disturbances. Histological data have shown that
      thick collagenous bundles are present in the sutural ligament, which may tether
      the osteogenic fronts, resulting in premature fusion. The hormone relaxin has
      been shown to disrupt collagen fiber organization, possibly preventing
      craniosynostosis by relaxing the sutural ligament and allowing osteogenic fronts
      to separate normally and stay patent. This study tested this hypothesis with a
      rabbit model of delayed-onset coronal suture synostosis. METHODS: A total of 18
      New Zealand White rabbits with craniosynostosis were randomly assigned to one of
      three groups: sham control, protein control (BSA), relaxin treatment. After
      initial diagnosis, sham surgery, BSA, or relaxin was delivered to the fusing
      coronal suture in a slow-release (56-day) collagen vehicle. Longitudinal
      radiographs and body weights were collected at 10, 25, 42, and 84 days of age,
      and sutures were harvested for histology. RESULTS: Relaxin-treated animals had
      more disorganized intrasuture content than control groups. These specimens also
      appeared to have relatively wider sutures ectocranially. There were no
      significant differences in relaxin-treated animals for all craniofacial growth
      measures, or suture separation compared with controls. CONCLUSIONS: These data do
      not support our initial hypothesis that the use of relaxin may rescue sutures
      destined to undergo premature suture fusion. These findings suggest that collagen
      fiber arrangement may not be important for suture fusion. This protein therapy
      would not be clinically useful for craniosynostosis.

PMID- 21740160
TI  - Postpalatoplasty Eustachian tube function in young children with cleft palate.
AB  - OBJECTIVE: To characterize Eustachian tube function using the forced response
      test in young children with cleft palate with or without cleft lip after
      palatoplasty with tympanostomy tubes inserted prepalatoplasty and compare these
      results with those of a 1986 study that evaluated a similar population using
      identical methods. SETTING: Outpatient research clinic. PATIENTS/PARTICIPANTS: A
      total of 34 children with cleft palate were tested at an average age of 18.6 +/-
      4.0 months. MAIN OUTCOME MEASUREs: Passive and active measures for the forced
      response test. RESULTS: Of the sample, 13 ears could not be tested, and tests on
      24 ears were incomplete. The forced response test showed that the passive
      Eustachian tube function parameters were similar to those of normal adults and
      children. The percentage of ears that showed tubal dilation with swallowing was
      60%. The active resistance and dilatory efficiency were similar to those of a
      normal adult population. CONCLUSIONS: A 1986 study of Eustachian tube function in
      postpalatoplasty subjects with cleft palate (37 ears) aged 15 to 26 months
      documented Eustachian tube dilation with swallowing in 84% of the ears. In the
      present study, which focused on a similar population, the frequency of tubal
      dilation was 60%. Nonetheless, both frequencies are significantly greater than
      the dilation frequency of 27% reported for 56 ears of subjects with cleft palate
      tested between 3 months and 18 years with tympanostomy tubes inserted for
      persistent otitis media with effusion. This suggests that dilation during the
      forced response test may be a prognostic marker for those children with cleft
      palate who will resolve their ear disease at an early age.

PMID- 21740161
TI  - Long-term, longitudinal follow-up of individuals with UCLP after the Gothenburg
      primary early veloplasty and delayed hard palate closure protocol: maxillofacial
      growth outcome.
AB  - OBJECTIVE: To study long-term maxillofacial development in a sample of patients
      born with unilateral cleft lip and palate. The patients' palatal repair had been
      performed according to a two-stage protocol with early velar closure and delayed
      hard palate surgery. DESIGN: Retrospective, longitudinal cohort study. SUBJECTS:
      The sample consisted of 50 consecutive patients with unilateral cleft lip and
      palate born from 1980 to 1989. All of them had been operated on at the
      Sahlgrenska University Hospital in Gothenburg, Sweden. METHODS: Certain maxillary
      casts as well as lateral roentgencephalograms, obtained at 5, 10, 16, and 19
      years of age, were analyzed. Results : Our patients' maxillofacial growth was
      very good even up to the final examination in early adulthood. We ascribe the
      advantageous midfacial morphology of our patients particularly to limited growth
      restriction from palatal scars due to the surgical protocol used in our cleft
      center. CONCLUSION: The two-stage protocol we advocate for repair of the palatal
      cleft resulted in very satisfactory growth outcome. A palatal scar, which might
      impair maxillary development, was created only by the velar surgery. If this scar
      is located close to the posterior border of the hard palate, it might result in
      less maxillary growth restriction than if it is positioned further anteriorly.

PMID- 21740162
TI  - The influence of orthodontic treatment on the Goslon score of unilateral cleft
      lip and palate patients.
AB  - OBJECTIVE: To assess the effect of orthodontic treatment on Goslon Yardstick
      outcome. DESIGN: Retrospective study. PATIENTS: A series of 66 consecutive
      patients born with a complete unilateral left lip and palate. Patients were
      sorted into a nontreatment group (n  =  47) and a treatment group (n  =  19).
      METHOD: Three assessors trained in the use of the Goslon Yardstick ranked the
      dental arch relationships of study casts taken at 6 and 9 years. RESULTS: There
      was only a fair agreement (kappa  =  .33) between 6- and 9-year Goslon Yardstick
      scores for the cohort of 66 patients, with a significant (p < .05) difference in
      the mean score at 6 years (3.17 +/- 0.8) and at 9 years (2.88 +/- 1.0). Removal
      of 19 subjects who had orthodontic inventions prior to taking of the 9-year-old
      study cast improved the agreement to moderate (kappa  =  .52). There was no
      significant difference (p > .05) in mean scores at 6 and 9 years (3.13 +/- 0.9
      and 3.17 +/- 1.03, respectively). The treatment group exhibited significant
      differences (p < .001) with mean Goslon Yardstick scores of 3.0 +/- 0.9 at 6 and
      2.25 +/- 0.45 at 9 years. CONCLUSIONS: The inclusion of patients who had received
      orthodontic treatment prior to taking of study casts being used for Goslon
      Yardstick scoring can result in a more favorable outcome. Patients who have
      received active orthodontic treatment prior to taking of dental casts should be
      excluded or accounted for in audits to assess primary cleft surgical outcome in
      patients with a unilateral cleft lip and palate.

PMID- 21740163
TI  - Incidence of residual oronasal fistulas: a 20-year experience.
AB  - OBJECTIVE: To determine the incidence and most frequent anatomical locations of
      residual oronasal fistulas in children with different types of clefts who were
      treated at the University Department of Maxillofacial and Oral Surgery in
      Ljubljana. DESIGN: Retrospective analysis of 857 consecutive patients with cleft
      born between 1984 and 2003. RESULTS: After primary surgical repair, 33 out of 857
      (3.9%) children had residual oronasal fistulas. The incidence of clinically
      significant fistulas that required surgical repair was 17 of 857 (2.0%). In
      children with unilateral cleft lip and palate (UCLP), bilateral cleft lip and
      palate (BCLP), or isolated cleft palate (CP), the incidence of palatal fistulas
      was 23 of 644 (3.6%). Of these palatal fistulas, 12 (1.9%) were clinically
      significant. Oronasal fistulas were most frequently found in children with BCLP
      (9 of 88, 10.2%), followed by UCLP (12 of 215, 5.6%) and CP (12 of 341, 3.5%). No
      fistulas were found in children with unilateral cleft lip and alveolar ridge. In
      10 cases (30.3%), the oronasal fistula remained in the alveolar ridge, in 11
      cases (33.3%) in the anterior part of the hard palate, and in 11 cases (33.3%) at
      the junction of the hard and soft palates. In one case (3%), the records were
      lost. CONCLUSION: The low incidence of oronasal fistulas is the result of a
      surgical technique and tensionless suturing, followed by a two-layer closure, two
      stage palate repair in BCLP and UCLP patients, and preoperative orthopedics in
      UCLP cases.

PMID- 21740164
TI  - Subperiosteal release of the floor of the mouth to correct airway obstruction in
      pierre robin sequence: review of 31 cases.
AB  - OBJECTIVE: The purpose of this study was to evaluate subperiosteal release of the
      floor of the mouth (SRFM) musculature to correct neonatal airway obstruction in
      children with Pierre Robin sequence and to compare this procedure with other
      surgical options available. METHODS: A retrospective chart review of patients who
      underwent a SRFM for neonatal severe airway obstruction unresponsive to
      conservative management was performed. Preoperative and postoperative oxygenation
      parameters, sleep studies, feeding difficulties, and long-term evolution were
      documented. RESULTS: Thirty-one consecutive patients between 1995 and 2009, 19
      boys and 12 girls, had an SRFM procedure to alleviate severe neonatal airway
      obstruction. Eight children were syndromic, 15 had associated malformations, and
      eight had an isolated Pierre Robin sequence. The airway obstruction was corrected
      with SRFM alone in 26 children (84%), three patients remained dependent on
      nasopharyngeal airway, and two required subsequent mandibular osteogenic
      distraction procedures following the SRFM to manage persistent obstruction. No
      patient required a tracheostomy. The average age at SRFM was 33 days, and the
      patients were kept intubated for an average of 6 days postoperatively. Average
      hospital stay after the surgery was 45 days, and 10 patients went home with
      gavage feeding. CONCLUSIONS: The SRFM is effective for the treatment of severe
      airway obstruction in patients with Pierre Robin sequence. The procedure is
      simple and has fewer complications and secondary procedures than other surgical
      options for correction of the airway obstruction.

PMID- 21740165
TI  - A very rare cause of asymmetric velopharyngeal incompetence: unilateral palate
      hypoplasia.
AB  - Asymmetric velopharyngeal incompetence (VPI) may be caused by neuromuscular
      disorders, trauma, tumor resection, cleft palate, or unilateral hypoplasia of the
      velum and pharynx. However, VPI due to isolated unilateral hypoplasia is
      extremely rare. In this case report, a 4-year-old girl with unilateral palate
      hypoplasia and her two-staged management is presented. The speech quality of the
      patient improved noticeably after these procedures. The first stage allowed us to
      make the second stage pharyngeal flap more conservatively than possible in a one
      stage procedure. We think that this two-step procedure could be an alternative to
      other methods in the treatment of asymmetric VPI.

PMID- 21740166
TI  - Transient appearance of tyrosine hydroxylase immunoreactive cells in the midline
      epithelial seam of the human fetal secondary palate.
AB  - OBJECTIVE: Transient immunoreactivity for tyrosine hydroxylase, which mediates
      the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine, in the
      midline epithelial seam between the bilateral palatal shelves was investigated in
      human fetuses. MATERIALS AND METHODS: Horizontal or frontal paraffin sections of
      two human fetuses at 9 and 15 weeks of gestation were used to examine the
      distribution of tyrosine hydroxylase-immunoreactive cells in regions of the
      entire head other than the brain. Immunohistochemical staining for S100 protein,
      calretinin, cytokeratin 14, and vimentin was examined using adjacent or near
      sections. RESULTS: Tyrosine hydroxylase-immunoreactive cells were large and
      densely distributed in the midline epithelial seam at the site of palatal fusion
      in fetuses at 9 weeks but not in fetuses at 15 weeks, in which the midline
      epithelial seam had already disappeared. No expression of S100 protein,
      calretinin, or vimentin was detected, but the midline epithelial seam was
      positive for cytokeratin 14. Tyrosine hydroxylase immunoreactivity was not
      detected in epithelia during the process of palatal fusion in mice from E 14.0 to
      15.0. CONCLUSIONS: These findings indicate that tyrosine hydroxylase
      immunoreactive cells in the midline epithelial seams are nonneural epithelial
      cells and suggest that the tyrosine hydroxylase is a novel factor involved in
      normal palatal formation, especially the fate of the midline epithelial seam in
      humans.

PMID- 21740167
TI  - Levy-Bercowski D, Abreu A, DeLeon E, Looney S, Stockstill J, Weiler M, Santiago
      PE. Complications and solutions in presurgical nasoalveolar molding therapy.
      Cleft Palate Craniofac J. 2009;46:521-8.

PMID- 21740168
TI  - Nasoalveolar molding: prevalence of cleft centers offering NAM and who seeks it.
AB  - INTRODUCTION: Nasoalveolar molding (NAM) is a treatment option available for
      early cleft care. Despite the growing debate about the efficacy of nasoalveolar
      molding, questions remain regarding its prevalence and the demographic
      characteristics of families undergoing this technique prior to traditional cleft
      surgery. OBJECTIVES: To determine the number of teams currently offering
      nasoalveolar molding and to identify salient clinical and sociodemographic
      variables in infants and families who choose nasoalveolar molding compared with
      those who choose traditional cleft care across three well-established cleft
      centers. RESULTS: Via phone surveys, 89% of the U.S. cleft teams contacted
      revealed that nasoalveolar molding is available at 37% of these centers. Chart
      reviews and phone correspondence with caregivers indicate that the average
      distance to the cleft center was 65.5 miles and caregiver age averaged 30.9 +/-
      5.7 years. Of families who chose nasoalveolar molding, 85% received total or
      partial insurance coverage. No difference in caregiver education, income, or
      distance to the clinic between treatment groups was found. On average, infants
      receiving nasoalveolar molding and cleft surgery had larger clefts and had more
      clinic visits than infants receiving traditional cleft surgery. Infants who were
      firstborn and those who did not have other siblings were more likely to receive
      nasoalveolar molding than were infants who were residing with other siblings.
      CONCLUSIONS: Currently more than one-third of U.S. cleft centers offer
      nasoalveolar molding. Although the cleft size was larger in the nasoalveolar
      molding group, no treatment group differences in education, income, and distance
      to the clinic were found.

PMID- 21740169
TI  - Effects of cleft type, facemask anchorage method, and alveolar bone graft on
      maxillary protraction: a three-dimensional finite element analysis.
AB  - OBJECTIVE: To investigate biomechanical effects of cleft type
      (unilateral/bilateral cleft lip and palate), facemask anchorage method (tooth
      borne and miniplate anchorage), and alveolar bone graft on maxillary protraction.
      DESIGN: Three-dimensional finite element analysis with application of orthopedic
      force (30 degrees  downward and forward to the occlusal plane, 500 g per side).
      MODEL: Computed tomography data from a 13.5-year-old girl with maxillary
      hypoplasia. INTERVENTION: Eight three-dimensional finite element models were
      fabricated according to cleft type, facemask anchorage method, and alveolar bone
      graft. MAIN OUTCOME MEASURE(S): Initial stress distribution and displacement
      after force application were analyzed. RESULTS: Unilateral cleft lip and palate
      showed an asymmetric pattern in stress distribution and displacement before
      alveolar bone graft and demonstrated a symmetric pattern after alveolar bone
      graft. However, bilateral cleft lip and palate showed symmetric patterns in
      stress distribution and displacement before and after alveolar bone graft. In
      both cleft types, the graft extended the stress distribution area laterally
      beyond the infraorbital foramen. For both unilateral and bilateral cleft lip and
      palate, a facemask with a tooth-borne anchorage showed a dentoalveolar effect
      with prominent stress distribution and displacement on the upper canine point. In
      contrast, a facemask with miniplate anchorage exhibited an orthopedic effect with
      more favorable stress distribution and displacement on the middle maxilla point.
      In addition, the facemask with a miniplate anchorage showed a larger stress
      distribution area and sutural stress values than did the facemask with a tooth
      borne anchorage. The pterygopalatine and zygomatico-maxillary sutures showed the
      largest sutural stress values with a facemask with a miniplate anchorage and
      after alveolar bone grafting, respectively. CONCLUSION: In this three-dimensional
      finite element analysis, it would be more advantageous to perform maxillary
      protraction using a facemask with a miniplate anchorage than a facemask with a
      tooth-borne anchorage and after alveolar bone graft rather than before alveolar
      bone graft, regardless of cleft type.

PMID- 21740170
TI  - Velopharyngeal dysfunction and 22q11.2 deletion syndrome: a longitudinal study of
      functional outcome and preoperative prognostic factors.
AB  - OBJECTIVE: To describe the effect of time after velopharyngoplasty on outcome and
      to search for preoperative prognostic factors for residual hypernasality in
      patients with 22q11.2 deletion syndrome. DESIGN: Retrospective chart review.
      SETTING: Tertiary hospital. PATIENTS: Patients with 22q11.2 deletion syndrome and
      velopharyngeal dysfunction who underwent a primary (modified) Honig
      velopharyngoplasty between 1989 and 2009. MAIN OUTCOME MEASURES: Clinically
      obtained perceptual and instrumental measurements of resonance, nasalance, and
      understandability before and after velopharyngoplasty. RESULTS: Data were
      available for 44 of 54 patients (81% follow-up), with a mean follow-up time of
      7.0 years (range, 1.0 to 19.4 years). During follow-up, 24 (55%) patients
      attained normal resonance and 20 (45%) had residual hypernasality or underwent
      revision surgery. Mean postoperative nasalance and understandability scores were
      closer to the norm than mean preoperative scores were (2.0 versus 5.5 standard
      deviations for the normal passage, 1.3 versus 8.1 standard deviations for the
      nonnasal passage, and score 2.3 versus 4.1 understandability). Serial
      measurements revealed that hypernasality only resolved an average of 5 years
      after surgery, and three patients whose resonance initially normalized later
      relapsed to hypernasality. Gender, age at surgery, lateral pharyngeal wall
      adduction, velar elevation, presence of a palatal defect, previous intravelar
      veloplasty, nasalance, understandability, adenoidectomy, hearing loss, and IQ
      were not able to predict poor outcome following primary velopharyngoplasty (all p
      > .05). CONCLUSIONS: In this chart review of patients with 22q11.2 deletion
      syndrome and velopharyngeal dysfunction, residual hypernasality persisted in many
      patients after velopharyngoplasty. None of the preoperative factors that were
      studied had prognostic value for the outcome.

PMID- 21740171
TI  - Dental anomalies in children born with clefts: a case-control study.
AB  - OBJECTIVE: To determine the presence of specific patterns of dental defects in a
      group of individuals born with clefts. DESIGN: Case-control. SETTING: Nossa
      Senhora do Loreto Municipal Hospital and Federal University of Rio de Janeiro
      Pediatric Dentistry Clinics, Rio de Janeiro, Brazil. PATIENTS: 642 radiographic
      and clinical records were evaluated for 321 cases and 321 controls. RESULTS:
      Individuals born with clefts presented considerably more dental anomalies in
      comparison with controls (p  =  .0001). The most frequent was tooth agenesis (n 
      =  53; p  =  .001), followed by supernumerary teeth (n  =  14; p  =  .11) and
      tooth malposition (n  =  11; p  =  .33). Regarding tooth agenesis, the upper
      lateral incisors were more frequently absent in the cleft group (31/86), and
      control individuals presented more agenesis of the mandibular second premolars
      (19/45). CONCLUSIONS: The higher prevalence of dental anomalies, especially
      number anomalies, opposite the cleft area, in individuals born with cleft lip
      and/or palate is the most common associated dental anomaly outside the cleft
      area.

PMID- 21740172
TI  - Cephalometric evaluation of airways after maxillary anterior advancement by
      distraction osteogenesis in cleft lip and palate patients: a systematic review.
AB  - OBJECTIVE: This study was conducted to review the changes in airways after
      maxillary anterior advancement by distraction osteogenesis in patients with cleft
      lip and palate. MATERIALS AND METHODS: Several electronic databases were
      searched. The selection criteria were set to include clinical trials and at least
      1 year of postsurgical data. The original articles were then retrieved and
      evaluated by two investigators to ensure that they met the selection criteria.
      The references were also hand searched for possible missing articles. RESULTS:
      Forty-three abstracts were found in the electronic searches. After the first set
      of selection criteria was applied to these abstracts, 14 articles were retrieved.
      After the final selection criteria, only four articles were finally selected.
      However, sample sizes of the selected articles were small, and the methodological
      quality of the studies was inadequate. All selected articles were consistent in
      that upper airway sizes increased and nasal resistance was reduced after
      distraction osteogenesis. CONCLUSIONS: Despite the consistency of increasing the
      upper airway size and reducing nasal resistance in the only four found articles,
      limitations of the studies merit caution in interpreting these findings. We
      conclude that there are insufficient prospective randomized controlled clinical
      trials to confirm these results.

PMID- 21740173
TI  - Prevalence of dental anomalies in nonsyndromic individuals with cleft lip and
      palate: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess whether individuals born with nonsyndromic oral clefts
      display a higher frequency of dental anomalies. DESIGN: A search of MEDLINE,
      BIREME, OVID ALL EMB Reviews, and The Cochrane Library was conducted. The
      methodologic quality of the papers selected was assessed and scored. Papers
      reporting observational controlled studies of nonsyndromic forms of oral cleft
      matched for dental anomalies in primary and/or permanent teeth were included
      without language restrictions. Eligible studies were scored as "A"-low risk of
      bias, "B"-moderate risk of bias, or "C"-high risk of bias and poor quality. Fixed
      and random effects models were used to aggregate individual odds ratios (OR) and
      to derive pooled estimates and 95% confidence intervals. RESULTS: Six studies
      fulfilled our selection criteria and were included in the meta-analysis. Three
      distinct subgroup analyses were carried out in terms of dental anomalies. In the
      tooth agenesis meta-analysis, a random effects model was used because of
      heterogeneity and showed a significant association between tooth agenesis and
      oral clefts (OR  =  12.31; 95% confidence interval [CI]  =  3.75 to 40.36). In
      the remaining analyses, the fixed effects model revealed a positive association
      between supernumerary (OR  =  4.99; 95% CI, 2.58 to 9.64) and crown morphologic
      abnormalities (OR  =  5.69; 95% CI, 3.96 to 8.19) with oral clefts. Most included
      studies were of low to moderate quality. CONCLUSION: Although general limitations
      in study design were observed, the evidence suggests that a higher number of
      dental anomalies in the permanent dentition are noted in individuals born with
      oral clefts.

PMID- 21740174
TI  - Positional plagiocephaly and excessive folic acid intake during pregnancy.
AB  - OBJECTIVE: To assess the relationship between high intake of folic acid and
      positional plagiocephaly. DESIGN: Retrospective case-control study with
      questionnaires administered in the clinic to biological mothers of children with
      positional plagiocephaly (PP group) and mothers of children without it (CO
      group). SETTING: Tertiary, institutional clinic. University Hospital of
      Maastricht, The Netherlands. PATIENTS, PARTICIPANTS:  EXCLUSION CRITERIA: mothers
      of children with syndromic disease or bone deformation and of children with
      clearly continuous forces on the skull (torticollis). A total of 94 mothers were
      included in the PP group (response rate: 85%), and 74 were included in the CO
      group (response rate: 75%). Final sample sizes were 75 in the PP group and 54 in
      the CO group. MAIN OUTCOME MEASURES: The recommended daily dosage of folic acid
      in The Netherlands is 400 ug. The primary outcome was folic acid dosage in
      relation to the recommended dosage. A secondary outcome was duration of folic
      acid intake in relation to the recommended period of use during pregnancy.
      RESULTS: In the PP group, 20% used double the recommended dosage of folic acid,
      compared with 6% in the CO group (p < .05). In the CO group, 59% used folic acid
      longer than recommended compared with 56% in the PP group (not significant).
      There were no differences in baseline characteristics except for gestational
      period: 39.5 weeks in the PP group and 37.9 in the CO group (p < .05).
      CONCLUSION: Excessive daily intake of folic acid during pregnancy is seen among
      mothers of positional plagiocephaly patients.

PMID- 21740175
TI  - Maternal perspectives: qualitative responses about perceived barriers to care
      among children with orofacial clefts in North Carolina.
AB  - OBJECTIVE: To examine maternal perceptions of barriers to care of children with
      orofacial clefts (OFC) in a population-based survey that solicited open-ended
      qualitative responses. DESIGN AND SETTING: In 2006, a combination mail/phone
      survey was sent to all mothers of children with OFC. The questionnaire included
      76 items. A final open-ended question was included for additional information
      about cleft-related care. The analysis included responses to the open-ended
      question and sociodemographic characteristics of the respondents. Qualitative
      responses were transcribed and entered into a qualitative software package for
      analysis, and common themes were elucidated. PARTICIPANTS/PATIENTS: The North
      Carolina Birth Defects Monitoring Program was used to identify all resident
      infants born with OFC from 2001 to 2004. Of 478 eligible mothers, 52.9% (n  = 
      248) responded to the survey, and 39.5% (n  =  98) responded to the final open
      ended question. MAIN OUTCOME MEASURES: Percentage reporting problems accessing
      care, frequency of positive and negative comments, and indicators of financial,
      personal, and structural barriers to care. RESULTS: Of the 98 respondents, the
      majority (n  =  95, 96.99%) were the biological mother. Almost 40% of mothers
      indicated that accessing primary craniofacial care was a problem. Of those citing
      perceived barriers to care, the major issues cited were financial, structural,
      and personal barriers. CONCLUSIONS: Collaborative efforts between craniofacial
      centers and teams, health care systems, and birth defects registries are
      warranted to reduce perceived barriers to care among families of children with
      OFC. Further exploration of the themes and factors associated with barriers to
      care and services is needed.

PMID- 21740176
TI  - Factors associated with parental adaptation to having a child with a cleft lip
      and/or palate: the impact of parental diagnosis.
AB  - OBJECTIVE: To investigate the impact of parental diagnosis of cleft lip and/or
      palate on factors associated with parental adaptation to having a child with a
      cleft. DESIGN: A mixed-methodological, quasi-experimental, causal-comparative
      research design. PARTICIPANTS: A total of 27 parents born with a cleft lip and/or
      palate and 27 parents born without a cleft lip and/or palate completed the study
      measures. OUTCOME MEASURES: The Ways of Coping Questionnaire, the Connor-Davidson
      Resilience Scale, the Interpersonal Support Evaluation List, and the
      Posttraumatic Growth Inventory were included along with a researcher-designed,
      cleft-specific questionnaire. RESULTS: The cleft-specific questionnaire revealed
      that parents born with a cleft lip and/or palate reported feelings of guilt
      significantly more often than did parents without a cleft lip and/or palate.
      Parents without a cleft reported feeling anxious significantly more often than
      did parents born with a cleft lip and/or palate. The qualitative aspect of the
      study yielded further between-group differences. The feeling that their own cleft
      related experiences influenced their adjustment to having a child with a cleft
      emerged as a dominant theme for parents born with a cleft; whereas, parents
      without a cleft lip and/or palate highlighted the importance of accurate
      information and positive interactions with clinicians in facilitating adjustment
      to their situation. No significant between-group differences were found on the
      standardized measures; however, the study's small sample size increases the risk
      of type II error and may account for the lack of significant findings.
      CONCLUSIONS: These findings appear to provide support for the widely held
      clinical opinion that parental diagnosis of cleft lip and/or palate impacts how
      parents cope with and adjust to their child's diagnosis.

PMID- 21740178
TI  - Voice low tone to high tone ratio, nasalance, and nasality ratings in connected
      speech of native Mandarin speakers: a pilot study.
AB  - OBJECTIVE: Voice low tone to high tone ratio (VLHR) is defined as the power ratio
      of a voice spectrum with a specific cut-off frequency. Previous studies have
      shown that there are significant correlations between VLHR and nasalance and
      hypernasality ratings in vowels. The correlation was investigated in this study
      using connected speech material. DESIGN: The Zoo Passage, the Rainbow Passage,
      the English Nasal Sentences, the Mandarin Nonnasal Sentences, and the Mandarin
      Nasal Sentences were used to acquire VLHRs, nasalance scores, and perceptual
      judgments of nasality. Each passage was recorded twice for averaging, and the cut
      off frequencies from 200 Hz to 1200 Hz were used to survey for the presence of
      optimal correlations with VLHR. Participants : Ten native Mandarin speakers with
      an English learning history of over 8 years were enrolled. Main outcome measures
      : VLHRs, nasalance scores, and hypernasality ratings. RESULTS: The correlations
      of VLHR with nasalance (rho  =  .76, p < .001, Spearman rank correlation) and
      nasality ratings (rho  =  .81, p < .001) were significant using a cut-off
      frequency of 300 Hz for the English passages. For the Mandarin Sentences, the
      optimal correlations of VLHR with nasalance (rho  =  .83, p < .001) and nasality
      ratings (rho  =  .79, p < .001) were identified using a cut-off frequency of 500
      Hz. CONCLUSION: The significant correlations of VLHR with nasalance and
      perceptual ratings of nasality using connected speech show that these approaches
      have a potential value in terms of basic and clinical application.

PMID- 21740177
TI  - Genetic studies in the Nigerian population implicate an MSX1 mutation in complex
      oral facial clefting disorders.
AB  - BACKGROUND: Orofacial clefts are the most common malformations of the head and
      neck, with a worldwide prevalence of 1 in 700 births. They are commonly divided
      into CL(P) and CP based on anatomic, genetic, and embryologic findings. A
      Nigerian craniofacial anomalies study (NigeriaCRAN) was set up in 2006 to
      investigate the role of gene-environment interaction in the origin of orofacial
      clefts in Nigeria. SUBJECTS AND METHODS: DNA isolated from saliva from Nigerian
      probands was used for genotype association studies and direct sequencing of cleft
      candidate genes: MSX1 , IRF6 , FOXE1, FGFR1 , FGFR2 , BMP4 , MAFB, ABCA4 , PAX7,
      and VAX1 , and the chromosome 8q region. RESULTS: A missense mutation A34G in
      MSX1 was observed in nine cases and four HapMap controls. No other apparent
      causative variations were identified. Deviation from Hardy Weinberg equilibrium
      (HWE) was observed in these cases (p = .00002). A significant difference was
      noted between the affected side for unilateral CL (p = .03) and bilateral clefts
      and between clefts on either side (p = .02). A significant gender difference was
      also observed for CP (p = .008). CONCLUSIONS: Replication of a mutation
      previously implicated in other populations suggests a role for the MSX1 A34G
      variant in the development of CL(P).

PMID- 21740179
TI  - MRI with synchronized audio to evaluate velopharyngeal insufficiency.
AB  - OBJECTIVE: To demonstrate the feasibility of simultaneous-acquired magnetic
      resonance imaging (MRI) and high-quality synchronized audio recording for
      evaluating velopharyngeal closure. DESIGN: Institutional Review Board-approved
      case series. SETTING: Tertiary care hospital. PATIENTS: Three healthy adult
      volunteers with a normal speech pattern. INTERVENTIONS: MRI with simultaneous
      recorded audio files evaluating velopharyngeal closure. MAIN OUTCOME MEASURE:
      Precise imaging and audio coordination of specific phonatory tasks. RESULTS:
      Synchronization of MRI and audio in all three adults. CONCLUSION: Our novel
      imaging and audio protocol provides simultaneous acquired MRI with synchronized
      high quality audio for evaluating velopharyngeal closure. This technique may
      provide the opportunity to improve diagnosis and surgical planning in patients
      with velopharyngeal insufficiency.

PMID- 21740180
TI  - Oculofaciocardiodental syndrome: a rare case and review of the literature.
AB  - Oculofaciocardiodental syndrome is a rare genetic disorder affecting ocular,
      facial, dental, and cardiac systems. The clinical diagnosis of
      oculofaciocardiodental syndrome can be challenging due to a wide variety of
      symptoms. Oculofaciocardiodental syndrome is found only in females due to its X
      linked inheritance pattern and embryonic lethality for males. Radiculomegaly of
      canines is the most consistent finding in these patients. In this report we
      present a female patient with characteristic facial features, as well as a
      comprehensive overview of oculofaciocardiodental syndrome. Diagnosis of
      oculofaciocardiodental syndrome in this patient was verified by genetic analysis,
      during which we found a novel mutation in BCOR.

PMID- 21740181
TI  - Patient satisfaction after prosthetic rehabilitation of bone-grafted alveolar
      clefts with nonsubmerged ITI Straumann dental implants loaded at three months.
AB  - OBJECTIVE: To assess clinical, aesthetic, and quality-of-life parameters of cleft
      lip and palate patients' implant-supported crowns with ITI Straumann nonsubmerged
      and loaded after 3 months implants. PATIENTS, MATERIAL, AND METHODS: In 17 bone
      grafted cleft patients, 24 implants were placed nonsubmerged, loaded at 3 months
      to support crowns in the cleft area, and followed up at 40 months on average (+/-
      22 months). The oral-health-related quality of life was assessed in all patients
      with the German Oral Health Impact Profile after implant therapy. Aesthetics were
      judged on photographs by dental professionals, nonprofessionals, and the patients
      themselves. The Implant Crown Aesthetic Index served as an objective tool.
      RESULTS: A total of 23 implants (95.8%) were loaded and in function. Clinical
      parameters were marginal bone loss of 1.15 +/- 2.16 mm, peri-implant probing
      depth of 2.56 +/- 0.66 mm, width of keratinized mucosa of 2.71 +/- 1.1 mm,
      mucosal recession of 0.41 +/- 0.8 mm, Periotest value of 0.18 +/- 6.5, and German
      Oral Health Impact Profile summary score of <= 2. The best aesthetic outcome was
      assessed by the patients themselves. Soft tissues were rated worse than were
      implant-supported crowns. CONCLUSIONS: Implant-borne prosthetic rehabilitation of
      bone-grafted clefts with nonsubmerged ITI Straumann implants with 3 months'
      loading represents a reliable treatment option with high success rates in the
      long term. Functional aspects are comparable to those of noncleft patients. The
      oral-health-related quality of life of cleft patients is similar to that of
      noncleft patients. Aesthetics are restricted but satisfactory to patients and
      dental professionals. Aesthetics of peri-implant soft tissues should be improved
      in the future.

PMID- 21740182
TI  - Pediatric craniofacial surgery: a review for the multidisciplinary team.
AB  - Pediatric craniofacial surgery is a specialty that grew dramatically in the 20th
      century and continues to evolve today. Out of the efforts to correct facial
      deformities encountered during World War II, the techniques of modern
      craniofacial surgery developed. An analysis of the relevant literature allowed
      the authors to explore this historical progression.   Current advances in
      technology, tissue engineering, and molecular biology have further refined
      pediatric craniofacial surgery. The development of distraction osteogenesis and
      the progressive study of craniosynostosis provide remarkable examples of this
      momentum. The growing study of genetics, biotechnology, the influence of growth
      factors, and stem cell research provide additional avenues of innovation for the
      future. The following article is intended to reveal a greater understanding of
      pediatric craniofacial surgery by examining the past, present, and possible
      future direction. It is intended both for the surgeon, as well as for the
      nonsurgical individual specialists vital to the multidisciplinary craniofacial
      team.

PMID- 21740183
TI  - Re.: Dental arch relationship outcomes in children with complete unilateral cleft
      lip and palate.

PMID- 21740184
TI  - Relationship between occlusion and lisping in children with cleft lip and palate.
AB  - INTRODUCTION: The literature suggests that individuals with history of cleft lip
      and palate who present with midfacial growth deficiency are at higher risk of
      presenting lisping. The relationship between distortions during production of
      linguoalveolar fricative sounds and the severity of malocclusion, however, has
      not been established for the population with cleft. OBJECTIVE: To study the
      association between lisping and dental arch relationship. METHODOLOGY: Speech
      samples and dental arch casts were obtained from 106 children with operated
      unilateral cleft lip and palate (UCLP) during the stage of mixed dentition and
      before orthodontic treatment. Videotaped productions of the phrase /u saci saiw
      sedu/ were rated by speech-language pathologists for the identification of
      lisping during [s]. Dental arch casts were rated by orthodontists using the
      Goslon Yardstick and the Five-Year Index to establish dental arch relationship.
      RESULTS: Multiple logistic regression showed no significant association between
      lisping and dento-occlusal index (p  =  .802) and age (p  =  .662). Substantial
      interjudge agreement during auditory-perceptual ratings was found (kappa  = 
      .63). Almost perfect agreement was found between orthodontists while establishing
      the dental arch relationship (kappa  =  .81). DISCUSSION: This study failed to
      reveal an association between lisping and dental arch relationship in children
      with operated UCLP. Multiple variables may play a role in determining occurrence
      of lisping, warranting further investigation.

PMID- 21740185
TI  - Alveolar bone morphology in patients with bilateral complete cleft lip and palate
      in the mixed dentition: cone beam computed tomography evaluation.
AB  - OBJECTIVES: To verify the thickness and level of alveolar bone around the teeth
      adjacent to the cleft by means of cone beam computed tomography (CBCT) in
      patients with complete bilateral cleft lip and palate prior to bone graft surgery
      and orthodontic intervention. METHOD: The sample comprised 10 patients with
      complete bilateral cleft lip and palate (five boys and five girls) in the mixed
      dentition. The mean age was 9.5 years, and all subjects showed a G3 interarch
      relationship according to the Bauru index. The thickness of alveolar bone
      surrounding the maxillary incisors and the maxillary canines was measured in CBCT
      axial section using the software iCAT Xoran System. The distance between the
      alveolar bone crest and the cement-enamel junction (CEJ) was measured in cross
      sections. RESULTS: The tomography images showed a thin alveolar bone plate around
      teeth adjacent to clefts. No bone dehiscence was observed in teeth adjacent to
      clefts during the mixed dentition. A slight increase in the distance between the
      alveolar bone crest and the CEJ was observed in the mesial and lingual aspects of
      canines adjacent to cleft. CONCLUSION: In patients with BCLP in the mixed
      dentition, teeth adjacent to the alveolar cleft are covered by a thin alveolar
      bone plate. However, the level of alveolar bone crest around these teeth seems to
      be normal, and no bone dehiscence was identified at this age.

PMID- 21740186
TI  - Demographics of cleft care providers in Africa and reported experience in
      training and practice: direct analysis of continent-based practitioners.
AB  - OBJECTIVE: To elucidate the impact of several geographic, cultural, and
      socioeconomic variables on cleft care delivery in Africa, and to investigate the
      current status of cleft care delivery in Africa. DESIGN: Survey of practitioners
      attending the second Pan-African Congress on Cleft Lip and Palate (PACCLIP).
      SETTING: The annual PACCLIP conference in Ibadan, Nigeria, West Africa, February
      2007. MAIN OUTCOME MEASURE: To provide an analysis of the demographics and
      training experience of cleft care providers in Africa by collating information
      directly from the continent-based practitioners. RESULTS: Plastic surgeons and
      oral and maxillofacial surgeons provide the majority of cleft care. Most of the
      participants reported availability of formal training programs in their
      respective countries. The predominant practice settings were university and
      government-based. During training, half of the providers had encountered up to 30
      cleft cases, and a quarter had managed more than 100 cases. Representation of
      visiting surgeons were equally distributed between African and non-African
      countries. CONCLUSIONS: This study provides initial and detailed analysis crucial
      to understanding the underlying framework of cleft care composition teams,
      demographics of providers, and training and practice experience. This awareness
      will further enable North American and other non-African plastic surgeons to
      effectively partner with African cleft care providers to have a further reaching
      impact in the region.

PMID- 21740187
TI  - Susceptibility of XPD and RAD51 genetic variants to carcinoma of urinary bladder
      in North Indian population.
AB  - For the present study, two polymorphisms, xeroderma pigmentosum, complementation
      group D (XPD) Lys751Gln and RAD51 135G/C were studied with regard to bladder
      cancer. For XPD Lys751Gln polymorphism, an increased risk of bladder cancer was
      found to be associated with the Gln variant allele (odds ratio [OR]=1.86, 95%
      confidence interval [CI]=1.27-2.73), on taking AA (Lys/Lys) as the referent
      genotype. In males, the XPD 751C (Gln) allele was found to be associated with a
      significantly increased risk (OR=2.33, 95% CI=1.52-3.56). The inhabitants of
      rural areas showed a significantly increased risk with the XPD Gln allele
      (OR=2.59, 95% CI=1.46-4.62) when compared with those of urban areas. In smokers
      (OR=5.30, 95% CI=2.42-11.68), alcohol drinkers (OR=4.33, 95% CI=2.17-8.70), and
      nonvegetarians (OR=2.21, 95% CI=1.26-3.87), the XPD Gln allele showed a
      significantly increased risk toward bladder cancer. For RAD51 135G/C
      polymorphism, no significant difference was observed in the allelic and genotypic
      frequencies. Even after stratification, no significant association could be seen.
      After stratifying histopathologically, the RAD51 CC genotype was associted with
      decreased risk in subjects having superficial stage (OR=0.51, 95% CI=0.27-0.99)
      and with those having G2 grade (OR=0.24, 95% CI=0.09-0.62) of bladder cancer. XPD
      polymorphism may be a predisposing factor, but the same cannot be said for RAD51
      gene polymorphism.

PMID- 21740188
TI  - The bladder tumor suppressor protein TERE1 (UBIAD1) modulates cell cholesterol:
      implications for tumor progression.
AB  - Convergent evidence implicates the TERE1 protein in human bladder tumor
      progression and lipid metabolism. Previously, reduced TERE1 expression was found
      in invasive urologic cancers and inhibited cell growth upon re-expression. A role
      in lipid metabolism was suggested by TERE1 binding to APOE, a cholesterol
      carrier, and to TBL2, a candidate protein in triglyceride disorders. Natural
      TERE1 mutations associate with Schnyder's corneal dystrophy, characterized by
      lipid accumulation. TERE1 catalyzes menaquinone synthesis, known to affect
      cholesterol homeostasis. To explore this relationship, we altered TERE1 and TBL2
      dosage via ectopic expression and interfering RNA and measured cholesterol by
      Amplex red. Protein interactions of wild-type and mutant TERE1 with GST-APOE were
      evaluated by binding assays and molecular modeling. We conducted a bladder tumor
      microarray TERE1 expression analysis and assayed tumorigenicity of J82 cells
      ectopically expressing TERE1. TERE1 expression was reduced in a third of invasive
      specimens. Ectopic TERE1 expression in J82 bladder cancer cells dramatically
      inhibited nude mouse tumorigenesis. TERE1 and TBL2 proteins inversely modulated
      cellular cholesterol in HEK293 and bladder cancer cells from 20% to 50%. TERE1
      point mutations affected APOE interactions, and resulted in cholesterol levels
      that differed from wild type. Elevated tumor cell cholesterol is known to affect
      apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer
      may represent a defect in menaquinone-mediated cholesterol homeostasis that
      contributes to progression.

PMID- 21740189
TI  - Effects of Mycobacterium tuberculosis ESAT-6/CFP-10 fusion protein on the
      autophagy function of mouse macrophages.
AB  - Autophagy plays specific roles in host innate and adaptive immune responses to
      numerous intracellular pathogens, including Mycobacterium tuberculosis. The ESAT
      6 and CFP-10 proteins are secreted by M. tuberculosis and play important roles in
      pathogenesis. We hypothesized that these two proteins may affect the autophagy
      function of host macrophages during infection with M. tuberculosis, thereby
      shaping the immune reaction toward the pathogen. Interestingly, we found that
      rapamycin-induced autophagy of macrophages infected with M. tuberculosis H37Rv
      enhanced localization of mycobacteria with autophagosomes and lysosomes. Ectopic
      expression of the ESAT-6/CFP-10 fusion in macrophages dramatically inhibited
      autophagosome formation, and M. tuberculosis survival inside infected macrophages
      was significantly affected as well. Further, M. tuberculosis viability was
      increased by the fusion protein. Expression levels of autophagy-related genes
      (ATG), especially atg8, also decreased (p<0.05). These results suggested that
      ESAT-6 and CFP-10 proteins play significant roles in autophagy formation in M.
      tuberculosis infection and that autophagosome formation is regulated through the
      expression of ATG.

PMID- 21740190
TI  - Calculated metabolic equivalents: a tool for exercise prescription among African
      American women.
AB  - BACKGROUND: Average daily steps (ADS) are a low-technology measurement of
      activity that is useful for exercise prescription. However, research demonstrates
      poor validity for ADS as a measure of exercise capability. We present a superior
      low-technology measure of exercise capability, which is easily applied by
      practitioners in clinical or nonclinical settings. METHODS: Based on analysis of
      baseline data from an intervention study to test a sustainable approach to long
      term physical activity improvement for employed African American women, between
      2005 and 2008, we examined exercise tolerance metabolic equivalents (METs) and
      ADS of 158 participants and generated an alternative measure of exercise
      capacity. We conducted regression analysis to determine the impact of key health
      indicators on exercise capacity and examined associations between our predictive
      model and true (MET) exercise performance. RESULTS: Using our predictive
      equation, 79.33% of participants were correctly categorized (very high, high,
      medium) based on our tool, with 10 women (6.67%) mischaracterized by one level
      higher than actual MET achievement and 21(14.00%) mischaracterized as one
      category lower than actual MET achievement. In contrast, using ADS alone resulted
      in 22.15% correctly categorized participants. CONCLUSIONS: The proposed tool is
      superior to existing low-technology measures of exercise capacity while retaining
      strong utility in nonclinical and low-resource settings.

PMID- 21740191
TI  - A qualitative study of perceived barriers to management of diabetes among women
      with a history of diabetes during pregnancy.
AB  - BACKGROUND: Uncontrolled diabetes during pregnancy can cause adverse maternal and
      infant outcomes. This study explored barriers to glycemic control before, during,
      and after pregnancy and describes knowledge, attitudes, and behaviors among
      pregnant women with pregestational diabetes (PGDM) or gestational diabetes (GDM).
      METHODS: Focus groups were conducted in the Atlanta area among white, black, and
      Hispanic women who had diabetes during a recent pregnancy. Participants were a
      convenience sample drawn from a variety of sources. Nine focus groups were held
      with women who had GDM, and seven focus groups were held with women who had PGDM.
      RESULTS: Participants identified five main areas of barriers to management of
      diabetes during pregnancy: financial barriers and difficulties accessing care,
      barriers to maintaining a healthy diet and exercising, communication
      difficulties, lack of social support, and barriers related to diabetes care.
      Participants with GDM had general awareness of possible diabetes complications
      but frequently could not name specific effects of diabetes on the woman or child
      during and after pregnancy. Most were unaware of their risk for developing type 2
      diabetes later. Participants with PGDM expressed concern about the increased risk
      of adverse outcomes for the baby; most knew the importance of maintaining
      glycemic control during pregnancy. Low rates of pregnancy planning were reported
      in both groups. Pregnancy planning was not identified as a strategy to ensure a
      healthy baby. CONCLUSIONS: The barriers to achieving glycemic control during
      pregnancy identified in this study could help inform future efforts to assist
      women in achieving optimal prepregnancy and intrapregnancy glycemic control.

PMID- 21740192
TI  - Signs and symptoms of suspected myocardial ischemia in women: results from the
      What is the Optimal Method for Ischemia Evaluation in WomeN? Trial.
AB  - BACKGROUND: Much of our understanding of gender differences in chest pain was
      derived from noncontemporary reports. The aim of the current report was to
      compare the frequency of chest pain by measures of ischemia in 824 women with
      suspected myocardial ischemia prospectively enrolled in a clinical trial of
      exercise testing with electrocardiography (ETT-ECG) alone compared to myocardial
      perfusion single photon emission computed tomography (SPECT) (ETT-MPS). METHODS:
      Women seeking evaluation of chest pain or anginal equivalent symptoms were
      randomized to ETT-ECG or ETT-MPS with Tc-99m tetrofosmin. The Women's Ischemia
      Syndrome Evaluation (WISE) and Seattle Angina Questionnaire (SAQ) chest pain and
      Duke Activity Status Index (DASI) questionnaires were employed in enrolled women.
      Higher SAQ scores denote improved symptoms or functioning. RESULTS: Eight hundred
      twenty-four women, average age 63 years, at intermediate-high coronary artery
      disease (CAD) likelihood were enrolled from 43 North American centers.
      Traditional cardiac risk factors were prevalent, with nearly half of women having
      a family history of premature coronary disease, hypertension, and hyperlipidemia.
      Chest pain symptoms occurring at least one to three times per week were reported
      in 60% of women. An examination of the SAQ domains revealed that although women
      reported minimal physical limitations (median, interquartile range [IQR] 88, 75
      100), there was a greater frequency of stable chest pain symptoms (median,
      IQR=40, 30-50). The majority of women (79%) reported moderate to heavy physical
      activity levels at home, with the average ETT and DASI estimated metabolic
      equivalents (METs) of 8.6+/-2.6 and 11.5+/-3.8. Women with more frequent daily
      episodes of chest pain were more likely to have a lower Duke Treadmill Score
      (DTS), 1 or mm of ST segment depression, and an abnormal MPS. CONCLUSIONS: The
      current report details a contemporary evaluation of female-specific
      symptomatology and measures of myocardial ischemia. Women reporting frequent
      angina were more likely to exhibit ischemia and this may characterize a female
      specific typical angina pattern.

PMID- 21740193
TI  - Sexual violence as a predictor of unintended pregnancy, contraceptive use, and
      unmet need among female youth in Colombia.
AB  - AIMS: Violence against women is an important risk factor for unintended pregnancy
      and contraceptive use, although less is known about this relationship among
      youth. This study aims to investigate linkages between sexual violence and
      unintended pregnancy among Colombian female youth (aged 13-24). METHODS: Using
      the nationally representative Colombian Demographic and Health Survey (2005), the
      association of sexual violence with unintended pregnancy, current modern
      contraceptive use, and unmet need for contraception is examined using Pearson's
      chi-square tests and logistic regression models. RESULTS: Of female youth who
      have been pregnant in the past 5 years, 13% report experiencing sexual violence
      during their lifetimes, with 6% reporting sexual violence perpetrated by a spouse
      or partner and 8% by someone else. Among female youth at risk of unintended
      pregnancy, sexual violence is reported by 11%. About 5% of these female youth
      report sexual violence from a spouse or partner, and 7% report being forced to
      have sex with someone else. In cross-tabulations, female youth who have
      experienced sexual violence report significantly higher levels of unintended
      pregnancy and unmet need for contraception and lower levels of current modern
      contraceptive use compared to those who have not experienced sexual violence. In
      multivariate logistic regression models, sexual violence is associated with
      increased risk for unintended pregnancy (adjusted odds ratio [AOR] 1.4, 95%
      confidence interval [CI] 1.1-1.8), unmet need for contraception (AOR 1.5, 95% CI
      1.1-2.0), and decreased likelihood of current contraceptive use (AOR 0.8, 95% CI
      0.6-1.0). CONCLUSIONS: This analysis indicates that sexual violence is pervasive
      in Colombia and is consistently linked to increased risk of unintended pregnancy
      among female youth. Because youth are particularly vulnerable to sexual violence
      and may have difficulty accessing services, preventive efforts and clinical
      responses should be specifically crafted to curb violence against young women as
      well as reduce the longitudinal impact of experiencing sexual violence.

PMID- 21740194
TI  - Renal function outcomes after laparoscopic renal cryoablation.
AB  - BACKGROUND AND PURPOSE: Laparoscopic cryoablation (LCA) has emerged as an
      alternative to conventional surgery for the management of a T(1) renal mass;
      however, only few data are available on its functional outcomes. We assessed
      renal function changes after LCA in patients with normal renal function (NRF) and
      preexisting chronic renal insufficiency (CRI). PATIENTS AND METHODS: Data of
      consecutive patients who were undergoing LCA between 2000 and 2008 at Duke
      University Medical Center were analyzed. Renal function parameters were obtained
      preoperatively, at discharge, and at 6, 12, and 24 months postoperatively. Serum
      creatinine (sCr) levels and estimated glomerular filtration rates (eGFR) were
      compared over a 2-year follow-up. RESULTS: Of 67 patients, 22 (33%) had CRI at
      baseline. These patients were older, had larger tumors (2.5 vs 2.0 cm, P=0.039),
      and a higher incidence of multiple lesions (22.7% vs 4.4%, P=0.034). Compared
      with baseline, sCr was significantly increased and eGFR declined at discharge, 6,
      12, and 24 months in both NRF and CRI groups. Median sCr increase was 0.1 mg/mL,
      eGFR declined by 4.2 mg/mL/1.73 m(2) in the CRI cohort and up to 8.8
      mg/mL/1.73m(2) in NRF patients (all P<0.05) during the follow-up. Compared with
      baseline, however, no significant changes were noted in the distribution of CRI
      categories at any time (all P>0.05). CONCLUSIONS: A minimal decline in renal
      function can be appreciated in patients undergoing LCA at midterm follow-up. This
      decline is no higher in CRI than in NRF patients. LCA offers excellent renal
      function outcomes at 2 years follow-up. Specifically, in patients with CRI, LCA
      offers excellent preservation of renal function.

PMID- 21740195
TI  - Clinical pathway for 3-day stay after robot-assisted cystectomy.
AB  - BACKGROUND AND PURPOSE: Typical lengths of stay after open cystectomy are 5 to 7
      days, without dramatic differences reported for laparoscopic or robot-assisted
      cystectomy. We developed a clinical pathway for early discharge after robot
      assisted cystectomy, attempting to take advantage of potentially decreased
      morbidity with this minimally invasive procedure and analyzed our initial
      outcomes. PATIENTS AND METHODS: The initial 30 consecutive patients undergoing
      robot-assisted cystectomy who were treated on a clinical pathway developed at our
      institution were reviewed. This included an extraction incision of <=3 inches
      also used for urinary diversion, no intensive care unit stay, no nasogastric
      tube, and avoidance of intravenous narcotics. Ambulation is begun on
      postoperative day (POD) zero, with clear liquids uniformly on POD 1, then regular
      diet on passing flatus. Patients are discharged when tolerating diet, with a
      target of POD 3. RESULTS: Mean age was 67 years (45-87 y), and mean operative
      time was 411 minutes. All ambulated by POD 1. Only 4 of 30 needed any intravenous
      narcotics. Twenty-one patients were discharged on POD 3 and 8 on POD 4 for an
      overall mean of 3.3 days, including 2 who were discharged on POD 2 and 1 on POD
      7. One was seen in the emergency department on POD 6 for emesis, and one was
      readmitted on POD 7 for candidal infection. No others returned to the clinic or
      hospital within a week after discharge (POD 10). CONCLUSION: Our clinical pathway
      after robot-assisted cystectomy allows shorter hospital stays than typical and
      is, to our knowledge, the shortest reported after cystectomy by any technique.
      Only two unplanned visits occurred during the first 10 days. Further experience
      will be necessary to confirm the initial success.

PMID- 21740196
TI  - Preliminary assessment of a renal tumor materials model.
AB  - PURPOSE: To evaluate a materials model for laparoscopic guided cryotherapy or
      radiofrequency tissue ablation (RFA) of kidney tumors through expert surgeon
      assessment. MATERIALS AND METHODS: During the inaugural American Urological
      Association 2010 Tissue Ablative course content, validity testing of a renal
      tumor model was undertaken. Five expert faculty in cryotherapy and RFA techniques
      for renal tumors performed laparoscopic ultrasonography (US) examination of the
      tumor model. They performed US guided placement and activation of the treatment
      probe into the tumor of the model. They completed a questionnaire and rated the
      quality of the renal tumor model on a 5 point Likert scale. RESULTS: All of the
      subjects assigned a score of 5 of 5 on the Likert scale regarding the ability to
      identify the tumor with US, were able to deploy the ablative probe into the model
      under US guidance, and would recommend the use of this teaching model to
      residents or fellows. They thought that this tumor model was appropriate for
      teaching laparoscopic US imaging of a renal tumor during ablative treatment
      procedures, teaching and practicing laparoscopic US-guided cryotherapy, and
      teaching and practicing laparoscopic US-guided RFA. CONCLUSION: We have developed
      a unique model that simulates small kidney tumors that can be used for training
      surgeons in ablative techniques.

PMID- 21740197
TI  - Pathologic evaluation of hemostatic agents in percutaneous nephrolithotomy tracts
      in a porcine model.
AB  - BACKGROUND AND PURPOSE: Hemostatic agents have been suggested as an adjunct for
      tubeless percutaneous nephrolithotomy (PCNL). We pathologically evaluated the
      percutaneous tracts injected with the fibrin sealant (FS) Evicel and hemostatic
      gelatin matrix (HGM) Surgiflo at various time intervals to determine their
      absorption and tract closure rates. We also evaluated whether these agents
      reduced urine leak rates in a porcine model. MATERIALS AND METHODS: Percutaneous
      access was obtained in 19 kidneys in 10 domestic swine. The tracts were dilated
      to 30F using a balloon dilating catheter. Ten kidneys served as controls.
      Surgiflo was injected into the tract of four kidneys, and Evicel was injected
      into the tract of five kidneys. Intravenous urography (IVU) was performed on
      postoperative days (POD) 1 and 10 to 14. IVU was performed on two pigs at POD 30.
      The pigs were sacrificed and kidneys were harvested for pathologic evaluation.
      RESULTS: Two (20%) control kidneys had a urine leak on IVU on POD 1. None of the
      kidneys treated with HGM or FS had a urine leak on POD 1. None of the kidneys had
      a leak on POD 10 to 14 or POD 30. On pathologic inspection, the tracts of all the
      control kidneys and HGM kidneys had closed completely at POD 14. Two kidneys
      treated with FS had fistula at POD 6 and POD 14. At POD 30, the tracts in the
      control kidneys and kidney treated with HGM had completely healed. Fibrin sealant
      remained in the tract at POD 30. CONCLUSION: Fibrin sealant should be used with
      caution because it can persist in the tract for up to 30 days and may inhibit
      wound healing. Hemostatic gelatin matrix is the preferable agent because the
      tract closed by POD 10 to 14, similar to the findings in the control animals. The
      use of hemostatic agents in a nephroscopy tract may reduce the risk of early
      urine leak after tubeless PCNL.

PMID- 21740198
TI  - Introduction: elder mental health: the next frontier.

PMID- 21740199
TI  - Mental health and aging in the 21st century.
AB  - This article reviews pressing issues in mental health care for older adults in
      the 21st century. After examining current forces for change in older adults'
      mental health care and coverage, the authors discuss barriers to accessing mental
      health care resulting from the fragmentation of the United States health care
      system as well as the history behind the multiple and competing systems of care
      for older adults. The article continues with a discussion of goals for the
      provision of good mental health service delivery for older adults and concludes
      by addressing potential responses and future target areas regarding mental health
      care for older adults as well as a potential realistic collaboration to address
      mental health and aging.

PMID- 21740200
TI  - Commentary: the forgotten older adult with serious mental illness: the final
      challenge in achieving the promise of Olmstead?
AB  - Older adults with serious mental illness disproportionately reside in nursing
      homes despite the U.S. Supreme Court Olmstead decision supporting the rights of
      persons with disabilities to benefit from integrated services in the community.
      This commentary addresses the neglected policy debate on implementing Olmstead
      for this rapidly growing, older population with special needs. First, the author
      describes research findings on older adults with serious mental illness living in
      nursing homes who might more appropriately reside and receive services in the
      community. Second, the author summarizes the evidence base for effective
      psychosocial rehabilitation interventions and services facilitating independent
      living in community settings for this subgroup. Finally, he concludes with seven
      policy recommendations aimed at advancing the promise of the Olmstead decision
      with respect to older adults with serious mental illness.

PMID- 21740201
TI  - Translating collaborative models of mental health care for older adults: using
      Iowa's experience to inform national efforts.
AB  - The Patient Protection and Affordable Care Act supports the translation of
      collaborative models of mental health care, but how the act will affect older
      adults remains unclear. The authors examined a sample of older Medicare
      beneficiaries and evaluated how individual characteristics, local service
      supplies, and other contextual features corresponded with the identification of
      older persons with psychiatric diagnoses and their access to specialty mental
      health care providers. Older adults presented a variety of psychiatric disorders,
      and their access and use of specialty mental health care related to age; sex;
      diagnosis; supply of mental health, health, and long-term care providers; and
      whether an older person lived in a rural area. Translation of collaborative
      models should consider a range of psychiatric conditions, adjust for varying
      local provider supplies, and consider the challenges in establishing
      collaborative care within rural areas.

PMID- 21740202
TI  - Treatment of late-life mental disorders in primary care: we can do a better job.
AB  - Health care services provided to older adults today are not as effective as they
      should be. The quality of care for late-life mental disorders often falls short
      of desired standards. The growth of the elderly population makes it imperative
      for the health care system to address late-life mental disorders more
      effectively. Intervention strategies based in primary care settings show the most
      promise, but effectiveness will depend on solving the geriatric psychiatry
      workforce crisis. Collaborative care is one promising model for improving
      geriatric mental health care delivery in primary care. Diffusion of collaborative
      care into the health care system and integrating geriatric psychiatry into other
      models such as geriatric medical homes will require redesign of the organization
      and financing of primary care and psychiatry to overcome current barriers. Public
      policy should reflect the essential role of psychiatry in geriatrics and promote
      the integration of geriatric psychiatry with primary care.

PMID- 21740204
TI  - Leveraging the PASRR process to divert and transition elders with mental illness
      from nursing facilities.
AB  - This study examines how some states use Pre-Admission Screening and Resident
      Review (PASRR) processes to provide opportunities for nursing facility diversion
      and/or transition for elders with mental illness and highlights potential
      promising practices from selected states. Document reviews and interviews were
      conducted with key informants across 13 states. Key themes presented are 1)
      philosophies of diversion/transition embedded into PASRR processes, 2) questions
      on screening tools used to promote diversion/transition, 3) PASRR authorities'
      collaboration with other initiatives to promote diversion/transition, and 4) the
      extent to which states used PASRR to help identify mental health supports needed
      by nursing facility residents. Findings provide policy-relevant information to
      help states consider enhancement of their PASRR processes to further support
      nursing facility diversion and transition for persons with mental illness and
      improved mental health services for those in nursing facilities.

PMID- 21740203
TI  - Nursing home admissions and long-stay conversions among persons with and without
      serious mental illness.
AB  - The appropriateness of nursing homes for individuals with serious mental illness
      remains a controversial issue in long-term care policy more than a decade since
      the landmark U.S. Supreme Court Olmstead decision in 1999 , which affirmed the
      rights of persons with disabilities to live in their communities. Using national
      nursing home Minimum Data Set assessments from 2005, the authors compared the
      demographic, clinical, and functional characteristics of persons with and without
      serious mental illness newly admitted to nursing homes. They found that newly
      admitted people with serious mental illness were younger and more likely to
      become long-stay residents than those admitted with other conditions, despite a
      higher proportion of residents with serious mental illness, including the
      elderly, classified as low-care status. The most substantial and clinically
      significant difference for rates of low-care status 90 days after initial
      admission are for persons younger than 65 with serious mental illness versus
      those younger than 65 without serious mental illness (33% vs. 8.5%, or 3.9 times
      greater). There is a notable difference in low-care status between persons aged
      65 and older with serious mental illness and those aged 65 and older without
      serious mental illness (14% vs. 6.6%, or 2.1 times greater). These results
      suggest that a substantial number of adults with serious mental illness residing
      in nursing homes may have the functional capacity to live in less restrictive
      environments.

PMID- 21740205
TI  - Coalitions on mental health and aging: lessons learned for policy and practice.
AB  - Elders with mental health needs have been poorly served. Private and government
      agencies have given this issue a low priority, which is reflected in service
      delivery and funding. Coalitions have developed in states around the country and
      have engaged in a variety of tasks, including training techniques and
      collaborative efforts to advocate successfully for appropriate services. While
      accomplishments vary, the coalitions should continue their work, and others
      should organize in order to reach the goal of having accessible and appropriate
      elder mental health services.

PMID- 21740206
TI  - Language matters: an introduction.
AB  - That language and sexuality are closely connected is one of the enduring themes
      in human sexuality research. The articles in this special issue of the Journal of
      Homosexuality explore some of these language-centered insights as they apply to
      same-sex related desires, identities, and practices and to other dimensions of
      non-normative sexual experiences. The articles address language use over a range
      of geographic and social locations. The linguistic practices discussed are
      diverse, including the language associated with Santeria, comments viewers make
      about gay pornography, homophobic discourse, coming out stories, stories where
      declarations of sexual identity are tacitly withheld, sexual messages in Black
      hip hop culture, assessments of urban AIDS ministries, and policies that limit
      transgender subjects' access to urban space. Taken together, these articles
      demonstrate that language matters in the everyday experience of sexual sameness
      and they model some of the approaches that are now being explored in language and
      sexuality studies.

PMID- 21740207
TI  - "The only dykey one": constructions of (in)authenticity in a lesbian community of
      practice.
AB  - This article demonstrates how members of a lesbian community of practice make
      interactional moves that allow them to position themselves as "authentically
      lesbian." Through the use of discourse analysis and a sociocultural linguistics
      focus on indexicality, the speakers are shown to invoke broadly accessible
      stereotypes and ideologies and to rework them in order to create locally
      specific, meaningful identities. This is achieved via mutually negotiated stance
      taking toward group-constructed, oppositional personae. Specifically, the women
      in this group position styles deemed as "girly" as inauthentic and antithetical
      to their concept of a lesbian--the authentic "dyke."

PMID- 21740208
TI  - Neoliberal homophobic discourse: heteronormative human capital and the exclusion
      of queer citizens.
AB  - In this article, I examine the relationship between homophobic language use and
      its broader social context, focusing on how a U.S.-based, conservative Christian
      organization's institutionalized homophobic text-making practices seek to derive
      legitimacy from the broader political economic discourses associated with the
      neoliberal moment. Using the Family Research Council's statement on marriage and
      the family as the basis for analysis, I demonstrate how the organization seeks to
      represent lesbian and gay subjects and their kinship formations as a threat to
      human capital development because they are based on affectional relationships
      that neither reflect nor respond to the kinds of self-governance and
      marketization that neoliberalism requires of all citizen-subjects and their
      families. Linguistic strategies for creating such representations include lexical
      choices that avoid overtly identifying lesbian and gay subjects as the object of
      discussion, the creation of a taxonomy for what constitutes "proper" families
      based on neoliberal principles--that implicitly excludes lesbian and gay kinship
      formations, and the use of neoliberal discourses of self-governance and
      marketization as the basis for that exclusion.

PMID- 21740209
TI  - Through a glass, darkly: U.S. marriage discourse and neoliberalism.
AB  - This article draws together research insights on marriage in the U.S. to argue
      that over the last 40 years we are able to see an active engagement with
      neoliberalism in discussions on the subject. Using discourse analysis, I consider
      how the underlying assumptions that inform the key concepts of autonomy,
      individualism, responsibility, and universality have been re-semanticized through
      neoliberal ideology to change the ways that Americans think of marriage (and
      themselves). In light of these changed assumptions, this article urges a
      reexamination of the activism and identity politics around marriage as well as
      further academic research on the topic.

PMID- 21740210
TI  - Black women queering the mic: Missy Elliott disturbing the boundaries of
      racialized sexuality and gender.
AB  - Though there were and always have been djs, dancers, graffiti artists, and
      rappers who were Black women, they are placed on the periphery of hip-hop
      culture; their voices, along with "gay rappers" and "white rappers" devalued and
      their contribution to the global rise of hip-hop either forgotten or eschewed.
      This article is an attempt to articulate the existence of Black women who work
      outside of the paradigms of the "silence, secrecy, and a partially self-chosen
      invisibility" that Evelynn Hammonds describes. At the center of this article lies
      an attempt to locate a new configuration and expression of desire and sexuality,
      opening a door, wide open, to gain a different view of Black women, their
      sexuality, their expression of it, and the complexities that arise when they
      attempt to express it in hip hop nation language.

PMID- 21740211
TI  - Drag queens' use of language and the performance of blurred gendered and racial
      identities.
AB  - Building on Barrett (1998), this study provides a sociolinguistic analysis of the
      language used by Suzanne, a European-American drag queen, during her on-stage
      performance in the southeastern United States. Suzanne uses wigs and costumes to
      portray a female character on stage, but never hides the fact that she is
      biologically male. She is also a member of a predominantly African-American cast.
      Through her creative use of linguistic features such as stylemixing (i.e., the
      use of linguistic features shared across multiple language varieties) and
      expletives, Suzanne is able to perform an identity that frequently blurs gender
      and racial lines.

PMID- 21740212
TI  - Coming Out a l'oriental: Maghrebi-French performances of gender, sexuality, and
      religion.
AB  - In this article, I examine issues of gender, sexuality, and religion for North
      African (Maghrebi)-French men in contemporary France. I introduce performance
      artist-photographer "2Fik," one of the Maghrebi-French research subjects from my
      2010 fieldwork, and examine excerpts of his particular coming out story to his
      parents and situate it in relation to recent work on homosexuality in the housing
      projects of France's banlieues [suburban neighborhoods] (Chaumont, 2009; Nait
      Balk, 2009). The interviewee's narrative interweaves a variety of discourses and
      imagery that help distinguish his experience from those found in those
      publications as well as in recent scholarship on sexuality, citizenship, and
      transnationalism (Cruz-Malave & Manalansan, 2000; Hayes, 2000; Leap &
      Boellstorff, 2004; Patton & Sanchez-Eppler, 2000; Provencher, 2007a). I argue
      that 2Fik's story and photography provide him a unique voice that draws on
      feminist and queer perspectives--informed by both reformed Islam and contemporary
      Western values--to "decline" (Rosello, 1998) and rewrite longstanding stereotypes
      of Islam in France. In fact, by acting as a "citizen-photographer" (Moller,
      2010), 2Fik successfully declines stereotypes including the absent Muslim father,
      the veiled woman, and the symbolic violence associated with heteronormativity and
      traditional masculinity in Maghrebi-French families.

PMID- 21740213
TI  - Word play, ritual insult, and volleyball in Peru.
AB  - Many gay men in the popular sectors of Lima, Peru participate in voley callejero,
      or street volleyball. The ethnographic data presented in this article describes
      verbal and corporal mechanisms through which gay identity emerges within the
      particular context of the street volleyball game, ultimately highlighting the
      contextual nature of identity. The volleyball players are not just hitting a ball
      back and forth, they are engaging in a meaningful activity that illuminates
      intersections of language, sexuality, and identity. Through the manipulation of
      the street into a volleyball court, the volleyball players create a space
      conducive to the articulation of particular verbal and embodied practices that
      index gay identity. The challenge to the regulations of "proper" volleyball
      through the practice of ritual insulting and the cultivation of gay volleyball
      technique are playful reconfigurations of gendered practices prominent in the
      sites where fieldwork was carried out.

PMID- 21740214
TI  - "This area has been declared a prostitution free zone": discursive formations of
      space, the state, and trans "sex worker" bodies.
AB  - The mayorally instituted and police-enforced Prostitution Free Zones in
      Washington, DC, serve as a tool of nation-state disciplinarity, wherein many
      transgender women of color, viewed as ideologically suspect, are profiled as "sex
      workers," facing police harassment and arrest. This article explores here how
      this process is not merely about sex work but rather about discourses that are
      evoked in the displacement of the always-already displaced-racial, sexed, and
      gendered "others" through interviews with activists and trans community members,
      as well as District of Columbia government publications.

PMID- 21740215
TI  - Go home, gay boy! Or, why do Singaporean gay men prefer to "go home" and not
      "come out"?
AB  - Anglo-American ontologies posit that gay men should come out to match their outer
      selves with their inner ones. In Confucianized Singapore, however, gay men
      refrain from coming out to their parents to avoid shaming their families.
      Instead, they couch their homosexuality in kinship terms and "go home" with their
      boyfriends (Chou, 2000). "Going home" gains familial acceptance, but it does not
      challenge mainstream discourses of homosexuality. By examining how Singaporean
      gay men negotiate their sexuality with their families, I question the validity of
      coming out and going home as both ontological discourses and strategies.

PMID- 21740216
TI  - The language of (in)visibility: using in-between spaces as a vehicle for
      empowerment in the family.
AB  - Drawing on 40 in-depth interviews with sexually nonconforming Latinas, this work
      looks at how these women negotiate family and achieve empowerment both through
      visibility and invisibility. This work explores the experiences of Latinas who
      verbally articulated their sexual nonconformity to their families as well as
      those who chose to maintain their relationships tacit. I offer that study
      participants found empowerment and agency not only through verbal articulation
      but also through tacit relationships and that sexually nonconforming Latinas
      inhabited an "in-between space" with their families that gave them the
      flexibility to pursue or not pursue visibility as they desired.

PMID- 21740217
TI  - "Maricon," "pajaro," and "loca": Cuban and Puerto Rican linguistic practices, and
      sexual minority participation, in U.S. Santeria.
AB  - Lesbian, gay, bisexual, and transgender (LGBT) people in Cuba, Puerto Rico, and
      the United States are, to varying degrees, practitioners of the Afro-Cuban
      religion popularly known as Santeria. Cuban and Puerto Rican forms of referencing
      LGBT populations are illustrated in this article, which is drawing from
      interviews and participant observation conducted in the United States, with close
      to 30 practitioners, many of whom were Cuban, Cuban American, and Puerto Rican. I
      discuss the ways in which Santeria gatherings produce an alternative use of
      otherwise stigmatized language for "gay" practitioners. Through the use of
      distinctive language to reference all of these populations, we may rethink the
      relationship between identities and practices, and within that, gender
      presentations vis a vis identities.

PMID- 21740218
TI  - "But of course he is led by God": pastoral influence on an HIV/AIDS ministry.
AB  - HIV/AIDS is spreading more rapidly in black communities than any other in the
      United States, with black women being 23 times more likely to become infected
      than any other subgroup in the country. Some African-American churches are
      becoming involved by creating HIV/AIDS ministries that cater to various needs of
      local populations. Through an examination of deictic markers, this article
      analyzes ideologies surrounding HIV/AIDS and the pastor's influence on the
      HIV/AIDS ministry at College Street Baptist Church.

PMID- 21740219
TI  - Language, gay pornography, and audience reception.
AB  - Erotic imagery is an important component of gay pornographic cinema,
      particularly, where work of audience reception is concerned. However, to assume
      the audience engagement with the films is limited solely to the erotic realm is
      to underestimate the workings of ideological power in the context and aftermath
      of reception. For example, the director of the film under discussion here (Men of
      Israel; Lucas, 2009b) intended to present an erotic celebration of the nation
      state. Yet, most viewers ignore the particulars of context in their comments
      about audience reception, placing the "Israeli" narrative within a broader
      framework, using transnational rather than film-specific criteria to guide their
      "reading" of the Israeli-centered narrative. This article uses as its entry point
      the language that viewers employ when describing their reactions to Men of Israel
      on a gay video club's Web site; this article shows how the work of audience
      reception may draw attention to a film's erotic details while invoking social and
      political messages that completely reframe the film's erotic narrative.

PMID- 21740220
TI  - Investigating sexuality discourses in the U.K. secondary English curriculum.
AB  - This article reports on findings from a small-scale study that investigated
      sexuality discourses in the U.K. secondary English curriculum. In addition to
      conducting a critical analysis of English curriculum documents, interviews were
      also conducted with some English teachers and young lesbian, gay, bisexual, and
      transgender (LGBT)-identified people who attended, or had recently left,
      secondary school in Birmingham, U.K. Key findings indicate that issues around
      sexual diversity are noticeably absent from the curriculum, while other forms of
      diversity are more visible. This means that teachers are not explicitly
      encouraged to explore sexual diversity in their teaching, and the effects of this
      on young LGBT-identified people are overwhelmingly negative.

PMID- 21740221
TI  - Queering the discourse of diversity.
AB  - In this article, we use corpus linguistic methods to examine why lesbian, gay,
      bisexual, transgender, and queer (LGBTQ) subjects are poorly recognized within
      diversity statements of U.K. and U.S. research universities. While universities
      position diversity as a marketable signifier, we argue that queerness is rendered
      invisible, lest its manifestation bring universities into disrepute. "Sexual
      orientation" appears as a "private" or "lifestyle" choice," and universities do
      not see it as part of their mission to enable students or employees to realize
      difference. We wish to propose that the language used in diversity statements
      should acknowledge notions of real inclusion and empowerment of those queers who
      work within them.

PMID- 21740222
TI  - Age-related macular degeneration with discordant late stage phenotypes in
      monozygotic twins.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a complex disease caused by
      genetic and environmental factors. Monozygotic twins with late stage AMD provide
      an opportunity to evaluate the role of environmental factors on a genetically
      uniform background. METHODS: Monozygosity was determined in four twin pairs by
      genotyping 15 highly polymorphic tetranucleotide repeat markers. Clinically, the
      monozygotic twin pairs were evaluated by ophthalmologic examination, fundus
      autofluorescence (FAF) imaging, and, upon suspicion of choroidal neovascular
      membranes, by fluorescein angiography. Twin pairs were followed over a period of
      4-8 years. RESULTS: Genetically confirmed monozygotic twins with early stages of
      AMD reveal striking symmetry of early macular pathology. Upon progression to late
      stage AMD each twin pair developed a discordant phenotype with respect to disease
      onset and specific phenotype as choroidal neovascularization (CNV) and geographic
      atrophy (GA). CONCLUSIONS: Genetic risk variants are known to predispose to the
      development of AMD. Course and visual outcome of the disease, however, appear to
      be influenced by environmental factors rather than genetic determinants.

PMID- 21740223
TI  - Consequences of age-related cognitive declines.
AB  - Adult age differences in a variety of cognitive abilities are well documented,
      and many of those abilities have been found to be related to success in the
      workplace and in everyday life. However, increased age is seldom associated with
      lower levels of real-world functioning, and the reasons for this lab-life
      discrepancy are not well understood. This article briefly reviews research
      concerned with relations of age to cognition, relations of cognition to
      successful functioning outside the laboratory, and relations of age to measures
      of work performance and achievement. The final section discusses several possible
      explanations for why there are often little or no consequences of age-related
      cognitive declines in everyday functioning.

PMID- 21740224
TI  - The evolutionary origins of friendship.
AB  - Convergent evidence from many species reveals the evolutionary origins of human
      friendship. In horses, elephants, hyenas, dolphins, monkeys, and chimpanzees,
      some individuals form friendships that last for years. Bonds occur among females,
      among males, or between males and females. Genetic relatedness affects
      friendships. In species where males disperse, friendships are more likely among
      females. If females disperse, friendships are more likely among males. Not all
      friendships, however, depend on kinship; many are formed between unrelated
      individuals. Friendships often involve cooperative interactions that are
      separated in time. They depend, at least in part, on the memory and emotions
      associated with past interactions. Applying the term "friendship" to animals is
      not anthropomorphic: Many studies have shown that the animals themselves
      recognize others' relationships. Friendships are adaptive. Male allies have
      superior competitive ability and improved reproductive success; females with the
      strongest, most enduring friendships experience less stress, higher infant
      survival, and live longer.

PMID- 21740225
TI  - Personality processes: mechanisms by which personality traits "get outside the
      skin".
AB  - It is time to better understand why personality traits predict consequential
      outcomes, which calls for a closer look at personality processes. Personality
      processes are mechanisms that unfold over time to produce the effects of
      personality traits. They include reactive and instrumental processes that
      moderate or mediate the association between traits and outcomes. These mechanisms
      are illustrated here by a selection of studies of traits representing the three
      broad domains of personality and temperament: negative emotionality, positive
      emotionality, and constraint. Personality processes are studied over the short
      term, as in event-sampling studies, and over the long term, as in lifespan
      research. Implications of findings from the study of processes are considered for
      resolving issues in models of personality structure, improving and extending
      methods of personality assessment, and identifying targets for personality
      interventions.

PMID- 21740226
TI  - Regulation of antigenic variation in Giardia lamblia.
AB  - Antigenic variation, a clonal phenotypic variation developed by microorganisms,
      involves the permanent switching of homologous, antigenically different cell
      surface molecules. In pathogenic microorganisms, antigenic variation is often
      described as a mechanism to evade the host immune system and therefore is
      responsible for the generation of chronic and/or recurrent infections. However,
      antigenic variation has also been involved in expanding host diversity and
      differential courses of the diseases. The intestinal protozoan parasite Giardia
      lamblia undergoes antigenic variation through the continuous exchange of
      approximately 200 variant-specific surface proteins. Here we review the principal
      issues regarding the significance of antigenic variation during Giardia
      infections, the particular features of the variant-specific surface proteins, and
      the current knowledge on the mechanisms that regulate this process, as well as
      the relevance of disrupting antigenic variation as a novel approach to design
      effective antiparasitic vaccines.

PMID- 21740227
TI  - Alternative pathways of carbon dioxide fixation: insights into the early
      evolution of life?
AB  - The fixation of inorganic carbon into organic material (autotrophy) is a
      prerequisite for life and sets the starting point of biological evolution. In the
      extant biosphere the reductive pentose phosphate (Calvin-Benson) cycle is the
      predominant mechanism by which many prokaryotes and all plants fix CO(2) into
      biomass. However, the fact that five alternative autotrophic pathways exist in
      prokaryotes is often neglected. This bias may lead to serious misjudgments in
      models of the global carbon cycle, in hypotheses on the evolution of metabolism,
      and in interpretations of geological records. Here, I review these alternative
      pathways that differ fundamentally from the Calvin-Benson cycle. Revealingly,
      these five alternative pathways pivot on acetyl-coenzyme A, the turntable of
      metabolism, demanding a gluconeogenic pathway starting from acetyl-coenzyme A and
      CO(2). It appears that the formation of an activated acetic acid from inorganic
      carbon represents the initial step toward metabolism. Consequently, biosyntheses
      likely started from activated acetic acid and gluconeogenesis preceded
      glycolysis.

PMID- 21740228
TI  - Epidemiological expansion, structural studies, and clinical challenges of new
      beta-lactamases from gram-negative bacteria.
AB  - beta-Lactamase evolution presents to the infectious disease community a major
      challenge in the treatment of infections caused by multidrug-resistant gram
      negative bacteria. Because over 1,000 of these naturally occurring beta
      lactamases exist, attempts to correlate structure and function have become
      daunting. Although new enzymes in the extended-spectrum beta-lactamase (ESBL)
      families are frequently identified, the older CTX-M-14 and CTX-M-15 enzymes have
      become the most prevalent ESBLs in global surveillance. Carbapenemases with
      either serine-based or zinc-facilitated hydrolysis mechanisms are posing some of
      the most critical problems. Most geographical regions now report KPC serine
      carbapenemases and the metallo-beta-lactamases VIM, IMP, and NDM-1, even though
      NDM-1 was only recently identified. The rapid emergence of these newer enzymes,
      with multiple beta-lactamases appearing in a single organism, makes the design of
      new beta-lactamase inactivators or beta-lactamase-stable beta-lactams all the
      more difficult. Combination therapy will likely be required to counteract the
      continuing evolution of these insidious enzymes in multidrug-resistant pathogens.

PMID- 21740229
TI  - Cyclin-dependent kinases in brain development and disease.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a multifaceted serine/threonine kinase
      protein with important roles in the nervous system. Two related proteins, p35 and
      p39, activate Cdk5 upon direct binding. Over the past decade, Cdk5 activity has
      been demonstrated to regulate many events during brain development, including
      neuronal migration as well as axon and dendrite development. Recent evidence also
      suggests a pivotal role for Cdk5 in synaptic plasticity, behavior, and cognition.
      Dysfunction of Cdk5 has been implicated in a number of neurological disorders and
      neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral
      sclerosis, Niemann-Pick type C disease, and ischemia. Hyperactivation of Cdk5 due
      to the conversion of p35 to p25 by the calcium-dependent protease calpain during
      neurotoxicity also contributes to the pathological state. This review surveys
      recent literature surrounding Cdk5 in synaptic plasticity and homeostasis, with
      particular emphasis on Cdk5 kinase activity under neurodegenerative conditions.

PMID- 21740230
TI  - Mechanisms of T cell development and transformation.
AB  - T cells are the key mediators in cell-mediated immunity. Their development and
      maturation involve a complex variety of interactions with nonlymphoid cell
      products and receptors. Highly specialized to defend against bacterial and viral
      infections, T cells also mediate immune surveillance against tumor cells and
      react to foreign tissues. T cell progenitors originate in the bone marrow and,
      through a series of defined and coordinated developmental stages, enter the
      thymus, differentiate, undergo selection, and eventually mature into functional T
      cells. The steps in this process are regulated through a complex transcriptional
      network, specific receptor-ligand pair interactions, and sensitization to trophic
      factors, which mediate the homing, proliferation, survival, and differentiation
      of developing T cells. This review examines the processes and pathways involved
      in the highly orchestrated development of T cell fate specification under
      physiological as well as pathological conditions.

PMID- 21740231
TI  - Force generation, transmission, and integration during cell and tissue
      morphogenesis.
AB  - Cell shape changes underlie a large set of biological processes ranging from cell
      division to cell motility. Stereotyped patterns of cell shape changes also
      determine tissue remodeling events such as extension or invagination. In vitro
      and cell culture systems have been essential to understanding the fundamental
      physical principles of subcellular mechanics. These are now complemented by
      studies in developing organisms that emphasize how cell and tissue morphogenesis
      emerge from the interplay between force-generating machines, such as actomyosin
      networks, and adhesive clusters that transmit tensile forces at the cell cortex
      and stabilize cell-cell and cell-substrate interfaces. Both force production and
      transmission are self-organizing phenomena whose adaptive features are essential
      during tissue morphogenesis. A new era is opening that emphasizes the
      similarities of and allows comparisons between distant dynamic biological
      phenomena because they rely on core machineries that control universal features
      of cytomechanics.

PMID- 21740232
TI  - The ins and outs of the epithelial to mesenchymal transition in health and
      disease.
AB  - The epithelial to mesenchymal transition (EMT) converts epithelial cells into
      migratory and invasive cells and is a fundamental event in morphogenesis.
      Although its relevance in the progression of cancer and organ fibrosis had been
      debated until recently, the EMT is now established as an important step in the
      metastatic cascade of epithelial tumors. The similarities between pathological
      and developmental EMTs validate the embryo as the best model to understand the
      molecular and cellular mechanisms involved in this process, identifying those
      that are hijacked during the progression of cancer and organ degeneration. Our
      ever-increasing understanding of how transcription factors regulate the EMT has
      revealed complex regulatory loops coupled to posttranscriptional and epigenetic
      regulatory programs. The EMT is now integrated into the systemic activities of
      whole organisms, establishing links with cell survival, stemness, inflammation,
      and immunity. In addition, the EMT now constitutes a promising target for the
      treatment of cancer and organ-degenerative diseases.

PMID- 21740233
TI  - Role of leucine-rich repeat proteins in the development and function of neural
      circuits.
AB  - The nervous system consists of an ensemble of billions of neurons interconnected
      in a highly specific pattern that allows proper propagation and integration of
      neural activities. The organization of these specific connections emerges from
      sequential developmental events including axon guidance, target selection, and
      synapse formation. These events critically rely on cell-cell recognition and
      communication mediated by cell-surface ligands and receptors. Recent studies have
      uncovered central roles for leucine-rich repeat (LRR) domain-containing proteins,
      not only in organizing neural connectivity from axon guidance to target selection
      to synapse formation, but also in various nervous system disorders. Their
      versatile LRR domains, in particular, serve as key sites for interactions with a
      wide diversity of binding partners. Here, we focus on a few exquisite examples of
      secreted or membrane-associated LRR proteins in Drosophila and mammals and review
      the mechanisms by which they regulate diverse aspects of nervous system
      development and function.

PMID- 21740234
TI  - Chronic nicotine administration impairs activation of cyclic AMP-response element
      binding protein and survival of newborn cells in the dentate gyrus.
AB  - Chronic intake of nicotine can impair hippocampal plasticity, but the underlying
      mechanism is poorly understood. Here, we demonstrate that chronic nicotine
      administration in adult rats inactivates the cyclic AMP-response element binding
      protein (CREB), a transcription factor that regulates neurogenesis and other
      plasticity-related processes necessary for learning and memory. Consequently, we
      showed that impaired CREB signaling is associated with a significant decline in
      the production of new neurons in the dentate gyrus. Combining retrovirus labeling
      with gene expression approaches, we found that chronic nicotine administration
      reduces the number of adult-generated granule neurons by decreasing the survival
      of newborn cells but not the proliferation of progenitor cells. Additionally, we
      found that retroviral-mediated expression of a constitutively active CREB in the
      dentate gyrus rescues survival of newborn cells and reverses the nicotine-induced
      decline in the number of mature granule neurons. Prolonged nicotine exposure also
      compromises CREB activation and reduces the viability of progenitor cells in
      vitro, thereby suggesting that nicotine may exert its adverse effects directly on
      immature cells in vivo. Taken together, these data demonstrate that inhibition of
      CREB activation is responsible for the nicotine-induced impairment of hippocampal
      plasticity.

PMID- 21740235
TI  - Characterization of epidermal growth factor-induced dysplasia in the adult rat
      subventricular zone.
AB  - Epidermal growth factor (EGF) is a mitogen widely used when culturing adult
      neural stem cells in vitro. Although proliferative effects can also be observed
      in vivo, intracerebroventricular infusion of EGF has been found to counteract
      neuronal determination and promote glial differentiation instead. However, EGF
      receptor activation has different effects on the subventricular zone (SVZ) in
      mice and rats, possibly because of species differences in SVZ cell composition.
      Specifically in the rat, EGF stimulation of the SVZ induces the formation of
      hyperplastic polyps. The present study aims at molecular and morphological
      characterization of these subventricular polyps. Using immunohistochemistry,
      electron microscopy, and gene expression analysis, we demonstrate in hyperplastic
      EGF-induced polyps an upregulation in protein expression of Sox2, Olig2, GFAP,
      nestin, and vimentin. We found polyp-specific dysplastic changes in the form of
      coexpression of Sox2 and Olig2. This highly proliferative, Sox2/Olig2
      coexpressing dysplastic cell type is >10-fold enriched in the hyperplastic polyps
      compared with control SVZ and most likely causes the polyp formation. Unique
      ultrastructural features of the polyps include a lack of ependymal cell lining as
      well as a large number of cells with large, light, ovoid nuclei and a cytoplasm
      with abundant ribosomes, whereas other polyp cells contain invaginated nuclei but
      fewer ribosomes. EGF also induced changes in the expression of Id genes Id1, Id2,
      and Id4 in the SVZ. Taken together, we here demonstrate dysplastic, structural,
      and phenotypical changes in the rat SVZ following EGF stimulation, which are
      specific to hyperplastic polyps.

PMID- 21740236
TI  - Effect of light activation on tooth sensitivity after in-office bleaching.
AB  - This clinical study evaluated the effects of light-emitting diode (LED)/laser
      activation on bleaching effectiveness (BE) and tooth sensitivity (TS) during in
      office bleaching. Thirty caries-free patients were divided into two groups: light
      activated (LA) and non-activated (NA) groups. A 35% hydrogen peroxide gel
      (Whiteness HP Maxx, FGM Dental Products, Joinville SC, Brazil) was used in three
      15-minute applications for both groups. For the LA group, LED/laser energy
      (Whitening Lase Light Plus, DMC Odontologica, Sao Carlos SP, Brazil) was used, in
      accordance with the manufacturer's directions. Two sessions of bleaching were
      performed at one-week intervals. Color was registered at baseline and after the
      first and second bleaching sessions using a Vita shade guide. Patients recorded
      TS on a 0 to 4 scale during bleaching and within the next 24 and 48 hours of each
      session. BE at recall each week and intensity of TS were evaluated by repeated
      measures analysis of variance (ANOVA) and Tukey tests (alpha=0.05). Tooth
      sensitivity was compared using the Friedman repeated measures analysis of
      variance by rank and the Wilcoxon sign-ranked test. Faster bleaching was observed
      for the LA group than for the NA group after the first session (4.8 and 3.8 shade
      guide units [SGUs]; p=0.0001). However, both techniques were capable of bleaching
      the same number of SGUs after the second bleaching session (p=0.52). Most of the
      LA group (53.3%) had sensitivity even 24 hours after each bleaching session, but
      only 26.6% from the NA group reported TS. The intensity of TS was similar for
      both groups immediately after bleaching but significantly higher for the LA group
      24 hours after each bleaching session (p=0.001). After two bleaching sessions,
      the use of LED/laser light activation did not improve bleaching speed. Persistent
      tooth sensitivity and higher tooth sensitivity after 24 hours of bleaching were
      observed when light activation was used.

PMID- 21740237
TI  - A systematic technique for carving amalgam and composite restorations.
AB  - Both amalgam and composite restorations can quickly and accurately be carved
      using a systematic technique. By following the outlined steps, anatomically
      accurate restorations can be easily achieved. Inlay wax is used as a training
      medium to negate the setting constraints and as a high fidelity simulation.

PMID- 21740238
TI  - Streptococcus mutans biofilm adhesion on composite resin surfaces after different
      finishing and polishing techniques.
AB  - This study evaluated Streptococcus mutans biofilm adhesion on the surface of
      three composite resins (nanofilled, Filtek Z350, 3M ESPE, Salt Lake City, UT,
      USA; nanohybrid, Vit-1-escence, Ultradent Products, South Jordan, UT, USA; and
      microhybrid, Esthet X, Dentsply, Milford, DE, USA) following different finishing
      and polishing techniques. Sixty standardized samples (6 * 3 mm) of each composite
      were produced and randomly divided into three finishing and polishing treatments
      (n=20): 1) control group: composite resin surface in contact with Mylar matrix
      strips with no finishing or polishing performed, 2) Sof-Lex aluminum oxide disc
      technique (3M ESPE, and 3) carbide bur finishing and Astrobrush polishing
      technique (Ultradent). Half the samples of each group were incubated in human
      saliva for 1 hour, and all the samples were subjected to S mutans (ATCC 35688)
      biofilm development. The mean log of CFU/mL present in the S mutans biofilm was
      calculated, and data were statistically analyzed by three-way analysis of
      variance and the Tukey test (p<0.05). Human saliva incubation promoted a
      significant increase of bacterial adherence on all three of the composites'
      surfaces, regardless of the polishing treatment performed (p<0.05). Of the three,
      the nanofilled composite (Filtek Z350) had the lowest bacterial adherence with
      each of the finishing and polishing techniques despite the presence or absence of
      human saliva (p<0.05). Mylar matrix strips (control group) promoted the lowest
      bacterial adhesion on the surface of the microhybrid and nanofilled composites in
      the absence of human saliva.

PMID- 21740239
TI  - Creating tight proximal contacts for MOD resin composite restorations.
AB  - OBJECTIVE: The purpose of this study was to compare proximal contact tightness
      (PCT) of MOD resin composite restorations placed with different matricing
      protocols. METHODS: Forty-five ivorine lower right first molars with standardized
      MOD cavities were equally divided into three groups according to the restoration
      protocol. Group 1: Sectional matrix (Standard matrix, Palodent, Dentsply) secured
      with a wedge (Premier Dental Products Co.) and separation ring (BiTine I,
      Palodent, Dentsply, York, PA, USA) was used to restore the mesial surface first
      and then removed and repeated for the distal surface. Group 2: Identical to group
      1, but separation rings were placed at both the mesial and distal sides (BiTine
      I+II, Palodent) prior to restoration. Mesial surface was restored followed by
      distal. Group 3: Walser matrix (O-form, Dr. Walser Dental GmbH) was used.
      Following composite resin restoration, PCT was measured using the tooth pressure
      meter. Data were analyzed using analysis of variance and a Tukey post hoc test
      (p<0.05). RESULTS: PCT values for mesial contacts were 2.99 +/- 0.47N for group
      1, 4.57 +/- 0.36N for group 2, and 3.03 +/- 0.79N for group 3. For the distal
      contacts, the values were 4.46 +/- 0.44N for group 1, 5.12 +/- 0.13N for group 2,
      and 0.76 +/- 0.77N for group 3. Significantly tighter contacts were obtained for
      mesial and distal contacts for group 2 compared to groups 1 and 3 (p<0.05). For
      groups 1 and 3, mesial contacts were not significantly different (p=0.993), while
      distal contacts for group 1 were significantly tighter (p<0.001). CONCLUSION:
      Within the limitations of this study, tighter contacts can be obtained when
      sectional matrices and separation rings are applied to both proximal surfaces
      prior to placement of the resin composite in MOD cavities.

PMID- 21740240
TI  - Effect of C-factor on microtensile bond strengths of low-shrinkage composites.
AB  - This study evaluated the microtensile bond strength (MU-TBS) of low-shrinkage
      composites with their corresponding adhesive systems, Filtek Silorane/Silorane
      adhesive (SIL, 3M ESPE AG, Seefeld, Germany) and Aelite LS/One-Step Plus (AL,
      BISCO Inc, Schaumburg, IL, USA) in cavities with different C-factors. Filtek
      Z250/Adper Single Bond Plus (Z, 3M ESPE, St Paul, MN, USA) was used as a control.
      METHOD: Standardized Class I cavities were prepared in extracted human molars
      after removing occlusal enamel. Cavities were assigned into six different C
      factors by applying nail polish to four walls, three walls, two walls adjacent to
      each other, two walls opposite to each other, one wall, or no walls. Resin
      composites with their corresponding adhesive systems were applied according to
      manufacturer instructions. Specimens were sectioned to obtain four rectangular
      beams from the center of the restorations and MU-TBS was measured. Data were
      analyzed by Weibull survival analysis. Shrinkage stresses of the resin composites
      were determined after 30 minutes from the start of light-curing using a
      tensometer testing machine. Flexure elastic modulus was determined using standard
      procedures, in accordance with ISO 4049. Data for shrinkage stress and elastic
      modulus were analyzed by one-way analysis of variance followed by a Tukey
      multiple-comparisons test (p<0.05). RESULTS: MU-TBS of both SIL and AL were not
      affected by different C-factors; however, the bond strength of Z decreased
      significantly when the C-factor increased. Shrinkage stress results were 0.94 +/-
      0.1, 1.79 +/- 0.18, and 2.14 +/- 0.23 MPa for SIL, AL, and Z, respectively. The
      flexural modulus of both the SIL and the AL was significantly lower than that of
      Z. CONCLUSIONS: Increasing C-factor did not negatively affect the bond strength
      of low-shrinkage composites.

PMID- 21740241
TI  - A comparison of conventional and new rubber dam systems in dental practice.
AB  - OBJECTIVE: Rubber dam is an important tool in dentistry-in the past as well as
      today. As a result of a lack of acceptance of the conventional system, introduced
      by Barnum in 1869, new systems were developed (eg, OptraDam(r) by Ivoclar
      Vivadent AG, Schaan, Liechtenstein). This system was advertised as being very
      comfortable and easy to use, without distracting clamps. The aim of this study
      was to investigate if a new rubber dam system would be better accepted by
      patients and dentists than the conventional one. MATERIALS AND METHODS: Two
      hundred patients from the Department of Conservative Dentistry and Periodontology
      received at least one treatment with the conventional rubber dam (Dental Dam,
      Coltene Whaledent, Langenau, Germany) and one with the new rubber dam
      (OptraDam(r), Ivoclar Vivadent). Staff/students and patients were asked to
      complete questionnaires with regard to the advantages and disadvantages of the
      particular system after every treatment. RESULTS: Among patients, students, and
      dentists in the dental school environment there is a high degree of acceptance of
      rubber dam in general. During the study there were only very few situations in
      which neither of the systems could be used. The conventional rubber dam was
      preferred by all patients, students, and dentists (p<0.0001). CONCLUSION: Our
      study confirms that there is a high degree of acceptance of the rubber dam when
      it is compulsory to use. The reasons for the refusal during the daily workload of
      a practice remain unclear, but appear to be independent of the material or design
      available. A new design does not necessarily imply better acceptance.

PMID- 21740242
TI  - Microleakage and marginal gap of adhesive cements for noble alloy full cast
      crowns.
AB  - Very limited comparative information about the microleakage in noble alloy full
      cast crowns luted with different types of adhesive resin cements is available.
      The purpose of this study was to evaluate the microleakage and marginal gap of
      two self-adhesive resin cements with that of other types of adhesive luting
      cements for noble alloy full cast crowns. Fifty noncarious human premolars and
      molars were prepared in a standardized manner for full cast crown restorations.
      Crowns were made from a noble alloy using a standardized technique and randomly
      cemented with five cementing agents as follows: 1) GC Fuji Plus resin-modified
      glass ionomer cement, 2) Panavia F 2.0 resin cement, 3) Multilink Sprint self
      adhesive resin cement, 4), Rely X Unicem self-adhesive resin cement with
      pretreatment, and 5) Rely X Unicem with no pretreatment. The specimens were
      stored in distilled water at 37 degrees C for two weeks and then subjected to
      thermocycling. They were then placed in a silver nitrate solution, vertically cut
      in a mesiodistal direction and evaluated for microleakage and marginal gap using
      a stereomicroscope. Data were analyzed using a nonparametric Kruskal-Wallis test
      followed by Dunn multiple range test at a p<0.05 level of significance. The Rely
      X Unicem (with or with no pretreatment) exhibited the smallest degree of
      microleakage at both tooth-cement and cement-crown interfaces. The greatest
      amount of microleakage was found for Panavia F 2.0 resin cement followed by GC
      Fuji Plus at both interfaces. No statistically significant difference in the
      marginal gap values was found between the cementing agents evaluated (p>0.05).
      The self-adhesive resin cements provided a much better marginal seal for the
      noble alloy full cast crowns compared with the resin-modified glass ionomer or
      dual-cured resin-based cements.

PMID- 21740243
TI  - Effects of different surface conditioning methods on the bond strength of
      composite resin to amalgam.
AB  - Repairing amalgam restorations with composite resins using surface conditioning
      methods is a conservative treatment approach. This study investigated the effects
      of different conditioning methods that could be used for repair of amalgam
      fractures. Amalgam (N=96) was condensed into cavities within autopolymerizing
      polymethylmethacrylate (PMMA), and the exposed surface of each specimen
      (diameter, 6 mm; thickness, 2 mm) was ground finished. The specimens were
      randomly divided into nine experimental groups (n=12 per group), depending on the
      conditioning method used. The control group had natural central incisors with
      amalgam (n=12). The combination of the following conditioning methods was tested:
      silicacoating (Sc), sandblasting (Sb), metal primers, coupling agents, fiber (Fb)
      application, and opaquers (O). Five types of silanes, metal primers, or adhesives
      (Visiobond [V], Porcelain Photobond [PP], Alloy Primer [AP], Unibond sealer [Us],
      ESPE-Sil [ES]), and four opaquers, namely, Clearfil St Opaquer (CstO), Sinfony
      (S), Miris (M), and an experimental Opaquer (EO-Cavex), were used. The groups
      were as follows: group 1, Sc+ES+S+V; group 2, Sc+ES+CstO+V; group 3, Sc+ES+M+V;
      group 4, Sc+ES+EO+V; group 5, Sb+AP+S; group 6, Sb+AP+PP+CstO; group 7,
      Sc+ES+S+Fb+V+Fb; group 8-control, SC+ES+V; and group 9, Etch+Sc+ES+S+Us. One
      repair composite was used for all groups (Clearfil Photo Bond Posterior, Kuraray,
      Tokyo, Japan). Shear bond strengths (SBSs) (MPa +/- SD) were evaluated after 5
      weeks of water storage (analysis of variance [ANOVA], Tukey honestly significant
      differences [HSD], alpha=0.05). Group 1 exhibited significantly higher values
      (35.5 +/- 4.1) than were seen in group 4 (19.4 +/- 8.9), group 6 (19.1 +/- 7.8),
      and group 8 (20.1 +/- 4.1) (p<0.05). Group 9 exhibited significantly lower values
      (8.3 +/- 3.4) than were noted in groups 1 to 3 (35.5 +/- 4.1; 27 +/- 12.5; 24.4
      +/- 5.1, respectively) (p<0.05). Group 7 (16.4 +/- 5.9) showed significantly
      lower values than were observed in group 1 (35.5 +/- 4.1) (p<0.05). Surface
      conditioning techniques affected the bond strengths of composite adhesion to
      amalgam. Experimental opaquer exhibited lower values. Leaving a small border of
      enamel around the restoration decreased the bond strength.

PMID- 21740244
TI  - Bonding of restorative materials to dentin with various luting agents.
AB  - The aim was to compare eight types of luting agents when used to bond six
      indirect, laboratory restorative materials to dentin. Cylinders of the six
      restorative materials (Esteticor Avenir [gold alloy], Tritan [titanium],
      NobelRondo [feldspathic porcelain], Finesse All-Ceramic [leucite-glass ceramic],
      Lava [zirconia], and Sinfony [resin composite]) were ground and air-abraded.
      Cylinders of feldspathic porcelain and glass ceramic were additionally etched
      with hydrofluoric acid and were silane-treated. The cylinders were luted to
      ground human dentin with eight luting agents (DeTrey Zinc [zinc phosphate
      cement], Fuji I [conventional glass ionomer cement], Fuji Plus [resin-modified
      glass ionomer cement], Variolink II [conventional etch-and-rinse resin cement],
      Panavia F2.0 and Multilink [self-etch resin cements], and RelyX Unicem Aplicap
      and Maxcem [self-adhesive resin cements]). After water storage at 37 degrees C
      for one week, the shear bond strength of the specimens (n=8/group) was measured,
      and the fracture mode was stereomicroscopically examined. Bond strength data were
      analyzed with two-factorial analysis of variance (ANOVA) followed by Newman
      Keuls' Multiple Range Test (alpha=0.05). Both the restorative material and the
      luting agent had a significant effect on bond strength, and significant
      interaction was noted between the two variables. Zinc phosphate cement and glass
      ionomer cements produced the lowest bond strengths, whereas the highest bond
      strengths were found with the two self-etch and one of the self-adhesive resin
      cements. Generally, the fracture mode varied markedly with the restorative
      material. The luting agents had a bigger influence on bond strength between
      restorative materials and dentin than was seen with the restorative material.

PMID- 21740246
TI  - Conservative approach for esthetic treatment of enamel hypoplasia.
AB  - This article describes a minimally invasive technique for removal of intrinsic
      enamel stains and discoloration. The technique is based on enamel microabrasion
      with application of an acid-abrasive gel. Treatment may be complemented with
      composite resin to compensate for the effects of acid or to finish the masking
      effect.

PMID- 21740247
TI  - Oocyst ingestion as an important transmission route of Toxoplasma gondii in
      Brazilian urban children.
AB  - Toxoplasmosis is a cosmopolitan protozoan infection. Data regarding risk factors
      for the post-natal acquisition of Toxoplasma gondii infection in childhood are
      limited. We conducted a serological survey for T. gondii IgG antibodies and
      associated risk factors in 1,217 children 4-11-yr-old from Salvador, Brazil,
      using a commercial ELISA kit; antibodies were found in 17.5% of the children. Age
      (OR  =  2.18; 95% CI: 1.50-3.17) and maternal schooling level (OR  =  0.62; 95%
      CI: 0.42-0.92) were negatively associated with infection. A greater number of
      siblings (OR  =  1.53; 95% CI: 1.12-2.09), cat at home (OR  =  1.54; 95% CI: 1.06
      2.24), house with non-treated piped water (OR  =  2.54; 95% CI: 1.22-5.31), and
      the absence of a flush toilet at home (OR  =  1.45; 95% CI: 1.04-2.01) were
      positively associated with T. gondii infection. Our data suggest that low
      socioeconomic levels and poor hygiene habits are important factors in favoring T.
      gondii infection.

PMID- 21740248
TI  - A longitudinal study of the control of renal and uterine hemodynamic changes of
      pregnancy.
AB  - We have determined the sequence and extent of maternal renal and uterine
      adaptation to pregnancy and examined the role of hormonal factors in their
      regulation. Renal bipolar diameter (RBD), renal artery resistance index (RARI),
      uterine artery pulsatility index (UAPI), and plasma relaxin, human chorionic
      gonadotropin (hCG), progesterone, estradiol, urea, and creatinine were measured
      longitudinally in women with normal spontaneous singleton pregnancies, in vitro
      fertilization (IVF) singleton pregnancies, ovum donation (OD) singleton
      pregnancies, and multiple pregnancies from prepregnancy to postpartum. There was
      a progressive increase in the RBD and the RARI and a decrease in the UAPI during
      pregnancy. These changes reversed toward prepregnancy levels by 6 weeks post
      delivery. There was no difference in the rate of change of RBD, RARI, and UAPI
      between spontaneous singleton, IVF singleton, OD singleton, and multiple
      pregnancies (p < 0.05), but relaxin was directly correlated to the RARI (r =
      0.654, p = 0.015), and progesterone was inversely correlated to uterine artery PI
      (r = 0.554, p = 0.049). These data show that renal size and resistance to blood
      flow increase with advancing gestation, whereas the uterine artery resistance
      declined with gestation. These changes may be influenced by relaxin and
      progesterone.

PMID- 21740249
TI  - Health-related quality of life after induction of labor versus expectant
      monitoring in gestational hypertension or preeclampsia at term.
AB  - OBJECTIVE: Gestational hypertension (GH) and preeclampsia (PE) are major
      contributors to maternal and neonatal morbidity and mortality. In GH or PE, labor
      may be either induced or monitored expectantly. We studied maternal health
      related quality of life (HR-QoL) after induction of labor versus expectant
      monitoring in GH or PE at term. We performed the HR-QoL study alongside a
      multicenter randomized controlled trial comparing induction of labor to expectant
      monitoring in women with GH or PE after 36 weeks. METHODS: We used written
      questionnaires, covering background characteristics, condition-specific issues,
      and validated measures: the Short-Form (SF-36), European Quality of Life (EuroQoL
      6D3L), Hospital Anxiety and Depression Scale (HADS), and Symptom Checklist (SCL
      90). Measurements were at the following time points: baseline, 6 weeks
      postpartum, and 6 months postpartum. A multivariate mixed model with repeated
      measures was defined to assess the effect of the treatments on the physical
      component score (PCS) and mental component score (MCS) of the SF-36. Analysis was
      by intention to treat. RESULTS: We analyzed the data of 491 randomized and 220
      nonrandomized women. We did not find treatment effect on long-term HR-QoL (PCS: p
      = 0.09; MCS: p = 0.82). The PCS improved over time (p < 0.001) and was better in
      nonrandomized patients (p = 0.02). CONCLUSION: Despite a clinical benefit of
      induction of labor, long-term HR-QoL is equal after the induction of labor and
      expectant management in women with GH or PE beyond 36 weeks of gestation.

PMID- 21740251
TI  - Radiation Resistance in Cancer Therapy: Meeting Summary and Research
      Opportunities: Report of an NCI Workshop held September 1-3, 2010.

PMID- 21740255
TI  - Predictors of helping profession choice and volunteerism among siblings of adults
      with mild intellectual deficits.
AB  - This study examined aspects of the sibling relationship that predicted helping
      profession choice and volunteerism in siblings of individuals with mild
      intellectual deficits at 3 points in adulthood: their mid-30s, early 50s, and mid
      60s. The 393 respondents were from the Wisconsin Longitudinal Study, a
      prospective, longitudinal study following participants from ages 18 to 64 years.
      Being an only sibling predicted greater helping profession choice for female but
      not male siblings. Being older than the brother or sister with mild intellectual
      deficits as well as having more contact with and feeling closer to that brother
      or sister predicted more volunteerism for female but not for male siblings.
      Earlier measures of contact and closeness were better predictors of volunteerism
      than concurrent measures.

PMID- 21740256
TI  - Association between fatigue and autistic symptoms in children with cri du chat
      syndrome.
AB  - In the current study, the authors examined whether the fatigue level of children
      diagnosed with cri du chat syndrome was associated with the expression of
      autistic symptoms. Sixty-nine children with cri du chat syndrome were compared
      with 47 children with moderate to severe intellectual disabilities who did not
      differ on intellectual severity. Participants were assessed using the Infant
      Sleep Questionnaire ( J. M. B. Morrell, 1999 ) for fatigue-level rating and the
      Childhood Autism Rating Scale ( E. Schopler, R. J. Reichler, & B. R. Renner, 1988
      ) for autism-level rating. In support of the authors' hypothesis, results
      indicated that children who exhibited high levels of fatigue were more likely to
      express high levels of autistic symptoms. Contrary to the authors' hypothesis,
      children in the comparison group who exhibited high levels of fatigue conferred
      the greatest vulnerability to the expression of autistic symptoms.

PMID- 21740258
TI  - Moving from family care to residential and supported accommodation: national,
      longitudinal study of people with intellectual disabilities.
AB  - Abstract A cohort of nearly 11,000 persons was traced over 8 years to determine
      those who had moved from family care and those who had remained. The majority
      (85%) continued to live with families, and, for two thirds (67%), no future move
      was deemed necessary. The 2 main predictors of moving were as follows: A need had
      been previously recorded and the family had used out-of-home respite services
      during the 8 years. However, just one quarter of those identified as needing to
      move had done so in the 8 years. Conversely, no prior indication of need had been
      recorded for two thirds of people who had moved in this period. The complexities
      of assessing need and equitably meeting demands are discussed.

PMID- 21740257
TI  - Caregiver report of executive functioning in a population-based sample of young
      children with Down syndrome.
AB  - The current study describes everyday executive function (EF) profiles in young
      children with Down syndrome. Caregivers of children with Down syndrome (n  =  26;
      chronological ages  =  4-10 years; mental ages  =  2-4 years) completed the
      Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P; G. A. Gioia,
      K. A. Espy, & P. K. Isquith, 2003 ), a caregiver report measure of
      everyday/functional EF skills in multiple domains. On the BRIEF-P, elevations
      were noted on a global EF composite as well as the Working Memory and
      Plan/Organize scales in particular (relative to norms developed for typically
      developing children of a similar mental age). These results suggest a specific
      pattern of EF weaknesses in young children with Down syndrome, consistent with
      the extant literature that has focused primarily on older individuals who have
      been tested using laboratory EF tasks.

PMID- 21740259
TI  - Designs and analyses of psychotropic and behavioral interventions for the
      treatment of problem behavior among people with intellectual and developmental
      disabilities.
AB  - A combination of behavioral and medication-based interventions has been the most
      effective form of treatment for reducing problem behavior in individuals with
      intellectual and developmental disabilities. Evaluating the 2 types of
      interventions in combination and separately may require that researchers adapt
      methods traditionally used to evaluate drug interventions for individuals without
      disabilities. Some methodological difficulties that arise when evaluating drug
      treatments with this population include the withholding of treatment from control
      groups, identifying large homogeneous samples of participants, predicting
      individual clinical responsiveness, and many others. The purpose of this article
      is to summarize the methodological problems that arise when studying drug
      behavior interactions among people with intellectual and developmental
      disabilities and to suggest alternative methods that may ameliorate these issues.

PMID- 21740261
TI  - Comparison of hand-assisted laparoscopy versus open and laparoscopic techniques
      in urology procedures: a systematic review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Hand-assisted laparoscopic surgery (HALS) is an integral
      part of the urologist's armamentarium. We aimed to perform a comprehensive meta
      analysis comparing HALS renal surgery with open and laparoscopic techniques.
      METHODS: A systematic review and meta-analysis of HALS renal procedures (donor
      nephrectomy, nephrectomy, or nephroureterectomy) from 1996 to 2007 was performed.
      RESULTS: Sixty-two studies of 30 donor nephrectomy, 21 radical nephrectomy, and
      14 nephroureterectomy procedures in 5446 patients were included in the analysis.
      In donor nephrectomy, estimated blood loss (EBL) was statistically significant
      for HALS vs the open and laparoscopic cohorts, -69.0 mL (95% confidence interval
      [CI], -129.7, -8.2) and -40.1 mL (95% CI, -68.2, -12.0), respectively. Length of
      stay (LOS) was shorter compared with the open group, -1.7 days (95% CI, -2.3, 
      1.1). For nephroureterectomy, EBL (-29.9 mL (95% CI, -242.3, 182.5)), and LOS (
      1.5 d [95% CI, -2.8, -0.3]) again favored HALS vs open procedures. Operating room
      (OR) time and warm ischemia time (WIT) were statistically significant in favor of
      HALS donor nephrectomy vs the laparoscopic cohort; -36.8 minutes (95% CI, -61.3, 
      12.3) and -1.3 minutes (95% CI, -1.8, -0.7), respectively. For radical
      nephrectomy, both EBL -232.9 mL (95% CI, -383.6, -82.2) and LOS -2.4 days (95%
      CI, -3.5, -1.3) were statistically significant, favoring HALS vs the open group.
      CONCLUSION: We report the largest meta-analysis of HALS renal surgery to date.
      When compared with open surgery, HALS allows for a significant decrease in EBL
      and LOS. Compared with laparoscopic donor nephrectomy, HALS resulted in a
      significant decrease in blood loss, OR time, and WIT.

PMID- 21740262
TI  - Impact of fast-track postoperative care on intestinal function, pain, and length
      of hospital stay after laparoscopic radical prostatectomy.
AB  - BACKGROUND AND PURPOSE: Postoperative recovery of intestinal function, ability to
      ambulate, and effective pain management are main features to establish an
      effective fast-track surgery model. We investigated pain scores, ambulation rate,
      and recovery of intestinal function in a cohort of patients who were undergoing
      laparoscopic radical prostatectomy (LRP). PATIENTS AND METHODS: Fifty patients
      who underwent LRP in our institution were randomized to receive either
      conventional or fast-track postoperative care. Postoperative intestinal function
      was quantified by clinical signs of intestinal motility. Ambulation data were
      collected by means of step-count devices. Pain scores were measured by a visual
      analog scale. Overall satisfaction and additional measures to describe patient
      satisfaction with the clinical course were used as quality-of-life variables.
      RESULTS: Fast-track patients had significantly earlier propulsive intestinal
      motility without increased intestinal complications. Enforced mobilization led to
      a significantly shorter period to first deflation/defecation. Despite
      significantly increased ambulation rates in the fast-track group, these patients
      reported significantly less pain sentience during a significantly shorter
      hospital stay. Overall satisfaction was significantly higher in the fast-track
      cohort during the hospital stay. CONCLUSION: With the implementation of fast
      track concepts for LRP, patients can be discharged to home earlier with fewer
      complications, lower pain scores, and an overall higher satisfaction with life.

PMID- 21740266
TI  - Purinergic receptors influence the differentiation of human mesenchymal stem
      cells.
AB  - Adult stem cells, including adipose tissue-derived mesenchymal stem cells (MSCs)
      or ectomesenchymal dental follicle cells (DFCs), attract considerable attention
      for their potential to differentiate into lineages, which are of major interest
      in the field of Regenerative Medicine. Purinergic receptors exert a wide range of
      biological actions in many cell and tissue types through extracellular
      nucleotides. Little is known about P2 receptors in adult stem cells and changes
      in their expression levels during differentiation. All known P2 receptors have
      been investigated, and a variety of P2X and P2Y receptor subtypes were detected
      in MSCs. Studies investigating intracellular calcium levels on receptor
      stimulation demonstrated that the found P2 receptors are metabolically active.
      Interestingly, up- or downregulation of several P2 receptor subtypes at gene and
      protein level was observed during adipogenic and osteogenic differentiation, and
      the effect on differentiation was directly influenced by both the application of
      agonists/antagonists and apyrase-induced nucleotide cleavage. Here, we show for
      the first time that the combination of several P2 receptors plays a role in the
      differentiation of adult stem cells. The expression pattern of the P2 receptors,
      as well as their fate in differentiation, varies in stem cells of mesenchymal
      origin if compared with stem cells of ectomesenchymal origin. The subtypes P2X6,
      P2Y4, and P2Y14 seem to be pivotal regulators in MSC commitment, as they are
      regulated in both adipogenic and osteogenic differentiation of adipose tissue
      derived stem cells and DFCs. These findings provide new insights into the
      differentiation processes and might reveal novel options to influence stem cell
      fate in future applications.

PMID- 21740267
TI  - 3-Hydroxyflavone improves the in vitro development of cloned porcine embryos by
      inhibiting ROS production.
AB  - UV-irradiation of oocytes during enucleation and serum starvation of donor cells
      during cell cycle synchronization may compromise the development competence of
      cloned embryos through excessive generation of reactive oxygen species (ROS).
      Here, we show that 3-hyroxyflavone (a flavonoid having hydroxyl group at 3 carbon
      position) inhibits UV- and serum starvation-induced ROS production in oocytes and
      donor cells, respectively, and thereby improves the in vitro development of
      cloned porcine embryos (p<0.05). In a parthenogenetic model, UV-irradiation for 5
      sec or more was found to reduce the in vitro development and quality of the
      embryo, which could be rescued by their culture in the presence of 3
      hydroxyflavone. The rescuing effect of 3-hydroxyflavone was associated with
      significant reduction in ROS level (14.4+/-1.0 vs. 47.1+/-6.7), increase in ERK
      signaling molecules by 2.1-fold, and decrease in Caspase3 expression by 3.2-fold.
      Culture of donor cells (18.5+/-1.4 vs. 13.0+/-1.7%) or cloned embryos (20.6+/-1.1
      vs. 12.2+/-1.1%) in the presence of 3-hydroxflavone also increased (p<0.05) the
      rates of blastocyst formation in cloned embryos produced by the nuclear transfer
      of serum-starved donor cells into recipient cytoplasts exposed to UV-irradiation
      during the enucleation step. Importantly, both parthenotes and cloned embryos
      cultured in the presence of 3-hydroxyflavone had significantly increased ability
      to expand, and contained a higher number of cells than those of the control group
      (p<0.05). These results suggest that 3-hydroxyflavone may be useful for improving
      the in vitro developmental potential of cloned embryos through inhibition of ROS
      production induced by the UV-irradiation of oocyte and/or the serum starvation of
      donor cells.

PMID- 21740268
TI  - Viable calves produced by somatic cell nuclear transfer using meiotic-blocked
      oocytes.
AB  - Somatic cell nuclear transfer (SCNT) has had an enormous impact on our
      understanding of biology and remains a unique tool for multiplying valuable
      laboratory and domestic animals. However, the complexity of the procedure and its
      poor efficiency are factors that limit a wider application of SCNT. In this
      context, oocyte meiotic arrest is an important option to make SCNT more flexible
      and increase the number of cloned embryos produced. Herein, we show that the use
      of butyrolactone I in association with brain-derived neurotrophic factor (BDNF)
      to arrest the meiotic division for 24 h prior to in vitro maturation provides
      bovine (Bos indicus) oocytes capable of supporting development of blastocysts and
      full-term cloned calves at least as efficiently as nonarrested oocytes.
      Furthermore, the procedure resulted in cloned blastocysts with an 1.5- and
      twofold increase of POU5F1 and IFNT2 expression, respectively, which are well
      known markers of embryonic viability. Mitochondrial DNA (mtDNA) copy number was
      diminished by prematuration in immature oocytes (718,585+/-34,775 vs. 595,579+/
      31,922, respectively, control and treated groups) but was unchanged in mature
      oocytes (522,179+/-45,617 vs. 498,771+/-33,231) and blastocysts (816,627+/-40,235
      vs. 765,332+/-51,104). To our knowledge, this is the first report of cloned
      offspring born to prematured oocytes, indicating that meiotic arrest could have
      significant implications for laboratories working with SCNT and in vitro embryo
      production.

PMID- 21740269
TI  - Changes in the somatotrophic axis in genetically identical dogs.
AB  - Because cloned dogs are genetically identical, variations among these animals can
      be a useful tool to elucidate mechanisms underlying phenotypic differences. To
      estimate the influence of genetic factors on phenotypic variation, changes in
      concentration patterns of growth hormone (GH), insulin like growth factor-1 (IGF
      1), and IGF binding protein 3 (IGFBP-3) were compared among cloned and age
      matched control dogs. In addition, the concentrations of GH and IGF-1 following
      administration of growth hormone releasing hormone (GHRH) and somatostatin (SRIF)
      were measured in both groups. In comparing hormone profiles, the control dogs had
      larger standard deviations from the means for GH, IGF-1, and IGFBP-3 than the
      clones. Also, the mean concentration of IGFBP-3 in clones was significantly lower
      than in the controls between 7 to 12 months of age, whereas the IGFBP-3 changes
      in clones and controls followed the same pattern. GHRH induced increased serum
      growth hormone concentration both in clones and controls. However, the
      concentration of IGF-1 was lower in clones than in controls, and larger standard
      variations were noted in the control group. In conclusion, the measured traits
      were more homogeneous in cloned animals than in controls, so cloned animals could
      be valuable for assessing effects of genotype and environment interactions.

PMID- 21740270
TI  - Enucleation of demecolcine-treated bovine oocytes in cytochalasin-free medium:
      mechanism investigation and practical improvement.
AB  - Demecolcine-assisted/induced enucleation has been used in nuclear transfer
      cloning procedures for many species, yet its mechanism of action remains unclear.
      Primarily because oocytoplasm protrusion induced by demecolcine is inhibited by
      the presence of cytochalasin, its use has had limited application. In this
      experiment, we investigated the microtubule and microfilament alterations in
      bovine oocytes after demecolcine and/or cytochalasin B (CB) treatments by
      immunocytochemical staining. We also examined mechanical enucleation of
      demecolcine-treated oocytes in cytochalasin-free medium. The results showed that
      demecolcine-treatment disrupts the balance between microtubule/microfilament
      interactions primarily by deleting microtubules and with little effect on the
      microfilaments that we believe accounts for the membrane protrusion. The CB
      treatment reduced the amount of microfilaments but had little effect on the
      microtubules. Most demecolcine-induced membrane protrusions disappeared when
      exposed to CB. Western blotting showed that CB treatment increases G-actin, which
      indicates a decrease in the microfilaments. High oocyte enucleation, survival,
      and developmental rates occurred when demecolcine-assisted enucleation was
      carried out in a CB-free solution. Higher blastocyst development rates and
      blastocyst cell numbers were achieved compared to control, indicating that CB is
      not necessary in the enucleation procedure of bovine oocytes. This study provides
      a clearer understanding of the mechanism for the demecolcine-induced oocyte
      membrane protrusion, and substantiates the practical use of demecolcine-assisted
      enucleation in a CB-free environment.

PMID- 21740271
TI  - In vitro HIV Type 1 infection indirectly alters CD127 expression on CD8(+) T
      cells.
AB  - Decreased expression of interleukin (IL)-7 receptor alpha (CD127) on CD8(+) T
      cells in progressive HIV disease suggests a role for CD127 regulation in HIV
      immunopathogenesis. The direct effect of HIV on CD127 expression has not been
      explored to explain these in vivo findings. Peripheral blood mononuclear cells
      (PBMCs) or isolated CD8(+) T cells from healthy individuals were cultured with
      either X4 (HIV-1(IIIB)), R5 (HIV-1(BaL)), dual tropic (HIV-1(CS204)), or
      replication-incompetent (HIV(8E5)) strains of HIV. Both X4 and R5 strains
      transiently decreased CD127 expression on CD8(+) T cells in PBMC cultures but had
      no effect on isolated CD8(+) T cell cultures. Isolated CD8(+) T cells exposed to
      either (1) PBMCs incubated with HIV and cultured in a transwell or (2)
      supernatants from PBMCs incubated with HIV resulted in decreased CD127
      expression. Under no conditions did the replication-incompetent HIV strain affect
      CD127 expression. As observed in vivo, infection of PBMCs with HIV in vitro
      results in the downregulation of CD127 surface expression on CD8(+) T cells.
      Collectively, these data indicate that soluble factor(s) released as a result of
      HIV infection regulate CD127 expression. Further elucidation of the mechanism(s)
      of CD127 downregulation will provide important insights into the
      immunopathogenesis of HIV disease.

PMID- 21740272
TI  - Near full-length sequence analysis of HIV type 1 BF recombinants from Italy.
AB  - Recombination between HIV-1 subtypes B and F has generated several circulating
      and unique recombinant forms, particularly in Latin American areas. In Italy,
      subtype B is highly prevalent while subtype F is the most common pure non-B
      subtype. To investigate the recombination pattern in Italian BF recombinant
      viruses, we characterized full-length sequences derived from 15 adult patients,
      mostly Italian and infected by the heterosexual route. One of the BF mosaics was
      a CRF29, three sequences clustered with low bootstrap values with CRF39, CRF40,
      and CRF42. With the exception of the CRF29-like sequence, the other recombination
      patterns were unique, but two possible clusters were identified. Analysis of the
      gp120 V3 domain suggested a possible link with subtype F from Eastern Europe
      rather than from Latin America, favoring the hypothesis of local recombination
      between clade B and F viruses over that of import of BF recombinants from Latin
      America. HIV-1 subtypes B and F appear prone to generation of unique recombinants
      in Italy, warranting epidemiological surveillance and investigation of a possible
      clinical significance.

PMID- 21740273
TI  - An isolated cryptic peptide influences osteogenesis and bone remodeling in an
      adult mammalian model of digit amputation.
AB  - Biologic scaffolds composed of extracellular matrix (ECM) have been used
      successfully in preclinical models and humans for constructive remodeling of
      functional, site-appropriate tissue after injury. The mechanisms underlying ECM
      mediated constructive remodeling are not completely understood, but scaffold
      degradation and site-directed recruitment of progenitor cells are thought to play
      critical roles. Previous studies have identified a cryptic peptide derived from
      the C-terminal telopeptide of collagen IIIalpha that has chemotactic activity for
      progenitor cells. The present study characterized the osteogenic activity of the
      same peptide in vitro and in vivo in an adult murine model of digit amputation.
      The present study showed that the cryptic peptide increased calcium deposition,
      alkaline phosphatase activity, and osteogenic gene expression in human
      perivascular stem cells in vitro. Treatment with the cryptic peptide in a murine
      model of mid-second phalanx digit amputation led to the formation of a bone
      nodule at the site of amputation. In addition to potential therapeutic
      implications for the treatment of bone injuries and facilitation of
      reconstructive surgical procedures, cryptic peptides with the ability to alter
      stem cell recruitment and differentiation at a site of injury may serve as
      powerful new tools for influencing stem cell fate in the local injury
      microenvironment.

PMID- 21740274
TI  - HIV type 1 subtype surveillance in central Kenya.
AB  - Human immunodeficiency virus 1 (HIV-1) infection is characterized by genetic
      diversity such that specific viral subtypes are predominant in specific
      geographic areas. To determine circulating subtypes of HIV-1 in different parts
      of central Kenya, a cross-sectional study was carried out on HIV-1-positive blood
      samples collected from consenting individuals in eight hospitals of Kenya's
      central province. Proviral DNA was extracted from peripheral blood mononuclear
      cells. Polymerase chain reaction and direct sequencing using primers generated
      from a highly conserved region of HIV-1 env gp41 were carried out. Ninety-six
      samples were successfully amplified and sequenced. Analysis of the sequences
      showed that a majority of them belonged to subtype A1 (67/96, 69.8%), followed by
      subtypes D (18, 18.7%) and C (11/96, 11.5%). Consistent with findings in other
      parts of Kenya, HIV-1 subtype A1 was the most dominant virus in circulation.
      Continued surveillance of circulating subtypes of HIV-1 in Kenya is important in
      determining the evolution of the HIV/AIDS epidemic in Kenya.

PMID- 21740275
TI  - Acid adaptation affects the viability of Listeria monocytogenes BCRC 14846 and
      Salmonella Typhimurium BCRC 10747 exposed to disinfectants at 25 degrees C and 40
      degrees C.
AB  - In the present study, Listeria monocytogenes BCRC 14846 and Salmonella
      Typhimurium BCRC 10747 were subjected to acid adaptation at pH 5.5 at 37 degrees
      C for 1 and 4 h, respectively. The viability of the acid-adapted cells of test
      organisms exposed to Clidox-S, a chlorine-containing disinfectant, and
      Quatricide, a quaternary ammonium compound, was examined and compared with that
      of the control cells at 25 degrees C and 40 degrees C. Results revealed that acid
      adaptation significantly enhanced the viability of L. monocytogenes and
      Salmonella Typhimurium exposed to the disinfectants under investigation. Both
      pathogens examined were more susceptible to Clidox-S and Quatricide at 40 degrees
      C than at 25 degrees C. Further, L. monocytogenes was more susceptible to
      Quatricide than Salmonella Typhimurium, whereas Salmonella Typhimurium was more
      susceptible to Clidox-S than L. monocytogenes.

PMID- 21740276
TI  - Comparison of maternal milk (breastmilk) expression methods in an African
      nursery.
AB  - OBJECTIVE: This study compares maternal milk volumes (MMVs) of Ugandan mothers
      whose infants were in a special care nursery and who used one of three maternal
      milk expression techniques: double electric breast pump, single non-electric
      manual breast pump, and hand breastmilk expression. SUBJECTS AND METHODS: A
      convenience sample of 161 Ugandan mothers of infants who were either too immature
      or ill to independently feed from the breast yet healthy enough to survive in an
      environment without ventilator support (birth weights, 0.84-3.8 kg) were assigned
      to one of three maternal milk expressions: Group 1, double electric breast pump
      (n=55); Group 2, single non-electric manual breast pump (n=59); and Group 3, hand
      breastmilk expression (n=47). Data were collected over a 7-day period (from day 1
      postpartum to day 7 postpartum), and mean MMVs were measured and compared among
      the groups. RESULTS: The mean daily MMVs were as follows: Group 1, mean=647 mL
      (SD=310); Group 2, mean=520 mL (SD=298); and Group 3, mean=434 mL (SD=291).
      Results from one-way analysis of variance revealed significant differences in the
      mean MMV based on the method of maternal milk expression (p=0.0019). Further
      analysis using Tukey's HSD Test revealed significant differences in the MMV
      between Groups 1 and 3 (p < 0.01), but not between Groups 1 and 2 or between
      Groups 2 and 3. CONCLUSIONS: Electric breast pumps provided the highest mean MMV;
      however, many mothers obtained adequate feeding volumes for their infants' daily
      nutritional needs with the single non-electric manual breast pump and hand
      breastmilk expression.

PMID- 21740277
TI  - Successful white hair removal with combined coloring and intense pulsed Light
      (IPL): a randomized clinical trial.
AB  - OBJECTIVE: The purpose of this study was to introduce adjunct therapy to intense
      pulsed light (IPL) and to assess it in terms of safety, expense, feasibility, and
      efficacy. BACKGROUND DATA: Currently there is no satisfactory, efficient method
      for long-term white hair removal. METHODS: We conducted a randomized clinical
      trial of hirsute patients with excessive white hair on the chin and cheeks. In
      addition to IPL, the patients were randomly assigned to have their white hair
      colored with either black eyeliner or black hair dye as an adjunct to IPL aided
      for of six sessions (with a 4-week interval between sessions). The primary
      efficacy outcome, which was defined as the outcome after six sessions of therapy,
      was scored as poor (<30%), fair (30?60%) or good (>60%) response to white hair
      removal in predefined areas. The secondary outcome was recurrence 6 months after
      the final therapy session. RESULTS: In the eyeliner group (n=31), 15 (48.4%)
      individuals showed a fair response, and 16 (51.6%) individuals showed a good
      response. In the color-dye group (n=31), 1 (3.2%), 17 (54.8%) and 13 (41.9%)
      participants scored poor, fair, and good, respectively. There were no differences
      in clinician judgment of the treatment success between the eyeliner and color-dye
      groups after the six therapy sessions (p=0.895). Thirty-one patients had 6 months
      of visits (11 in the hair dye and 20 in the eyeliner group). Three participants
      in the color-dye group and five participants in the eyeliner group failed to show
      improvement 6 months after the laser surgery. There was no distinguishable
      pattern of failure between the two study groups (p=1). CONCLUSION: This study
      supports that hair coloring is an efficient and feasible technique that can be
      combined with IPL to eliminate white facial hair.

PMID- 21740278
TI  - Isointricatinol, a new antioxidant homoisoflavonoid from the roots of Caesalpinia
      digyna Rottler.
AB  - A new homoisoflavonoid, isointricatinol (1), together with eight known
      homoisoflavonoids, three flavonoids, bergenin and 11-O-galloylbergenin were
      isolated from the EtOAc fraction of MeOH extract of Caesalpinia digyna roots and
      evaluated for the antioxidant activity against DPPH and ABTS free radicals. The
      structure of 1 was elucidated by various spectroscopic techniques and found to be
      a Z-isomer of 7,8-dihydroxy-3-(4'-methoxybenzyl)chroman-4-one. Compound 1 was
      found to exhibit mild to moderate free radical scavenging effect against DPPH
      (IC(50), 85.50 uM) and ABTS (IC(50), 44.13 uM) radicals.

PMID- 21740279
TI  - Serotonin 2A receptor antagonists for treatment of schizophrenia.
AB  - INTRODUCTION: All approved antipsychotic drugs share an affinity for the dopamine
      2 (D(2)) receptor; however, these drugs only partially ameliorate the symptoms of
      schizophrenia. It is, therefore, of paramount importance to identify new
      treatment strategies for schizophrenia. AREAS COVERED: Preclinical, clinical and
      post-mortem studies of the serotonin 5-HT(2A) system in schizophrenia are
      reviewed. The implications of a combined D(2) and 5-HT(2A) receptor blockade,
      which is obtained by several current antipsychotic drugs, are discussed, and the
      rationale for the development of more selective 5-HT(2A) receptor antagonists is
      evaluated. Moreover, the investigational pipeline of major pharmaceutical
      companies is examined and an Internet search conducted to identify other
      pharmaceutical companies investigating 5-HT(2A) receptor antagonists for the
      treatment of schizophrenia. EXPERT OPINION: 5-HT(2A) receptor antagonists appear
      to assume an intermediate position by being marginally superior to placebo but
      inferior to conventional antipsychotic drugs. Three previous 5-HT(2A) receptor
      antagonists have been discontinued after Phase II or III trials, and available
      Phase IIa data on the remaining 5-HT(2A) receptor antagonist will need
      substantial additional validation to be approved as a new treatment strategy
      against schizophrenia.

PMID- 21740280
TI  - Protective effects of baicalin and quercetin on an iron-overloaded mouse:
      comparison of liver, kidney and heart tissues.
AB  - Excessive accumulation of iron in the body can lead to organ injury. Some
      flavonoids which possess high affinity to iron can be used as iron chelators for
      curing iron overload diseases such as haemochromatosis. In this article, the
      effects of baicalin and quercetin on different mouse tissues (liver, kidney and
      heart) afflicted with iron overload-induced injury were studied. It was found
      that after administration of 500 mg kg-1 iron dextran for 45 days, the degree of
      oxidative injury in the three organs was different. When iron dextran-induced
      iron-overloaded mice were fed a diet containing baicalin or quercetin (1% w/w),
      both flavonoids showed significant effects in suppressing iron overload-induced
      injury. The efficiencies of both flavonoids on different tissues varied. Both
      flavonoids caused a significant decrease of iron content in liver and kidney
      tissues but not in the heart, whereas the flavonoids were more efficient in
      inhibiting the increase of carbonyl content and the thiobarbituric acid reactive
      substance levels in heart tissues. The results indicate that the protective
      effects of baicalin and quercetin on different tissues of iron-overloaded mice
      are different.

PMID- 21740281
TI  - Studies on the detoxification effects and acute toxicity of a mixture of cis-sec
      butyl-1-propoenyl disulphide and trans-sec-butyl-1-propoenyl disulphide isolated
      from crude essential oil of Ferula sinkiangensis K.M. Shen, a Chinese traditional
      herbal medicine.
AB  - There have, so far, been no papers about the detoxification effects on morphine
      dependent animals of a mixture of cis-sec-butyl-1-propoenyl disulphide and trans
      sec-butyl-1-propoenyl disulphide (SBD), which is isolated from crude essential
      oil of Ferula sinkiangensis K.M. Shen, a Chinese traditional herbal medicine.
      Naloxone-precipitated abstinent morphine-dependent models and naturally abstinent
      morphine-dependent models were used to evaluate the detoxification effects of
      intraperitoneal injection of SBD. In addition, the writhing test for mice was
      used to assess the anti-nociceptive effects of SBD, and the spontaneous activity
      test was used to verify the sedative effects of SBD. Acute toxicity tests of the
      SBD in mice were performed and the LD50 values were calculated. The results
      indicated that SBD can inhibit the abstinent syndromes, and that SBD had good
      anti-nociceptive and sedative effects.

PMID- 21740282
TI  - Antihyperglycaemic and hypolipidaemic effects of the methanolic extract of
      Caralluma tuberculata in streptozotocin-induced diabetic rats.
AB  - The antihyperglycaemic and hypolipidaemic effects of the methanolic extract of
      Caralluma tuberculata were investigated in streptozotocin (STZ)-induced diabetic
      rats. The antihyperglycaemic activity was assessed by the reduction in fasting
      blood glucose (54% at 4th week) and the peak of blood glucose at 120?min of an
      oral glucose tolerance test in diabetic rats. Further, the tested extract also
      increased plasma insulin by 206.8%. The hypolipidaemic action of the extract was
      evident by the significant decrease in the levels of total cholesterol,
      triglycerides and LDL-cholesterol by 41.5%, 36.7% and 49.1%, respectively,
      compared to diabetic rat values. Interestingly, the extract increased the cardio
      protective lipid HDL-cholesterol by 147.97% as compared to diabetic rat value.
      The present data suggests that the methanolic extract of C. tuberculata has both
      antihyperglycaemic and hypolipidaemic effects in STZ-induced diabetic rats that
      may need further studies to be used in the management of diabetes and associated
      hyperlipedaemia.

PMID- 21740283
TI  - Thujone corrects cholesterol and triglyceride profiles in diabetic rat model.
AB  - Thujone, which is the major constituent in Salvia sp. (Lamiaceae), was found to
      correct the lipid profile (cholesterol and triglycerides) in diabetic rats. Oral
      treatment with thujone (5 mg kg-1 body weight dose) significantly adjusted
      cholesterol and triglyceride levels in diabetic rats (p <= 0.05) to normal levels
      compared to diabetic untreated rats. This provides a premise in the field of
      finding new agents to treat diabetic complications.

PMID- 21740284
TI  - Antifungal activity of sakurasosaponin from the root extract of Jacquinia
      flammea.
AB  - The methanolic crude extract from the roots of Jacquinia flammea showed moderate
      antifungal activity against dermatophytes and very strong antifungal activity
      against Colletotrichum gloeosporioides. The bioassay-guided purification of the
      extract, using a combination of vacuum-liquid chromatography and high performance
      liquid chromatography, allowed the identification of sakurasosaponin as the main
      metabolite responsible for the antifungal activity.

PMID- 21740285
TI  - Effect of olive pomace extracts on hyperlipidaemia.
AB  - In this study, we have examined the hypolipidemic effect of olive pomace
      extracts. Identification and quantitation of maslinic acid and oleanolic acid as
      the potentially effective components of the pomace extracts were carried out by
      high performance liquid chromatography methods. Hyperlipidaemia was induced in
      male Sprague Dawley rats by feeding them with a high cholesterol diet for 30
      days. The olive pomace extracts were supplemented (200 mg kg-1 body wt day-1) for
      15 days. The levels of serum total cholesterol, triglyceride, high density
      lipoprotein-cholesterol, low density lipoprotein-cholesterol, aspartate
      aminotransferase and alanine aminotransferase increased in rats with
      hyperlipidaemia. Treatment with the olive pomace extracts significantly modulated
      the abnormalities induced by hyperlipidaemia. Lipid accumulation was decreased in
      histological findings. This study provides the possibility of utilising the olive
      pomaces for the prevention and treatment of hyperlipidaemia.

PMID- 21740286
TI  - Evaluation of antileishmanial, cytotoxic and antioxidant activities of essential
      oils extracted from plants issued from the leishmaniasis-endemic region of Sned
      (Tunisia).
AB  - In this study, we tested 10 essential oils (EOs) extracted from 10 plants issued
      from Sned region (Tunisia) to evaluate both their leishmanicidal effects against
      Leishmania major and L. infantum, and their cytotoxicity against murine
      macrophage cell line RAW 264.7 (ATCC, TIB-71). The antioxidant activity was also
      monitored by the DDPH method, while the chemical composition of active EO was
      assessed by GC-MS analysis. The results showed that the EOs obtained from Thymus
      hirtus sp. algeriensis (rich on monoterpenoids, especially linalool at 17.62% and
      camphor at 13.82%) is significantly active against both L. major and L. infantum,
      whereas Ruta chalepensis EO (rich on 2-undecanone at 84.28%) is only active
      against L. infantum. Both oil extracts showed low cytotoxicity towards murine
      macrophages. The characteristic ratios (IC80 Raw264.7 cells/IC50 L. infantum and
      IC80 Raw264.7 cells/IC50 L. major) were, respectively, 2.7 and 1.57 for T. hirtus
      sp. algeriensis, and 1.34 and 0.19 for R. chalepensis. However, when measuring
      the antioxidant effects (DDPH method), the two latter EOs presented a moderate
      2,2-diphenyl-2-picrylhydrazyl hydrate scavenging effects compared to EOs from
      Eucaliptus globulus, Pinus halepensis, Pituranthos tortuosus, Rosmarinus
      officinalis, Tetraclinis articulata or to BHT.

PMID- 21740287
TI  - Hypolipidaemic and antioxidant activities of Ficus microcarpa (L.) in
      hypercholesterolemic rats.
AB  - Saponifiable and unsaponifiable fractions of Ficus microcarpa leaves hexane
      extract have been phytochemically studied and evaluated for its hypolipidaemic
      and antioxidant effects in hypercholesterolemic rats. The effect of the extract
      on the lipid profile was assessed by measuring the levels of total cholesterol,
      high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol
      (LDL-C), triglycerides, phospho and total lipids. Lipid peroxides, glutathione
      and superoxide dismutase were measured as antioxidants. The work was extended to
      evaluate liver function indices as well as the histopathological picture of the
      liver after treatment. Treatment with leaves extract (500 mg kg-1 body weight) 5
      times/week for 9 weeks at the same time of cholesterol administration (30 mg/0.3
      mL 0.7% tween/animal) recorded an improvement of lipid profile, antioxidants,
      liver function enzymes and the liver histopathological picture. The lipoidal
      matters of the unsaponifiable fraction of the hexane extract by GC/MS led to the
      identification of 22 compounds, while saponifiable fraction by (MS/MS) technique
      led to identification of 13 unsaturated and saturated fatty acid methyl ester
      derivatives. It can be concluded that the hexane extract of F. microcarpa L has
      been proved to have hypolipidaemic and antioxidant effects in
      hypercholesterolemic rats through its role in counteracting LDL oxidation,
      enhancement of HDL synthesis and inhibition of lipid peroxidation.

PMID- 21740288
TI  - Combination antiresorptive and osteoanabolic therapy for osteoporosis: we are not
      there yet.
AB  - Osteoanabolic therapy is theoretically and practically an appealing therapeutic
      option for men and postmenopausal women with osteoporosis because bone formation
      is directly stimulated, an action that is not shared by any antiresorptive agent.
      Parathyroid hormone (PTH), in the form of the full-length molecule (PTH[1-84])
      and its fully active but truncated amino-terminal fragment teriparatide (PTH[1
      34]), belong to this osteoanabolic class. Both formulations of PTH increase bone
      mineral density, increase biochemical markers of bone turnover, and reduce
      fracture incidence. They improve skeletal microstructure. While antiresorptive
      agents are considered by most to be first line for the treatment of osteoporosis,
      there are situations when anabolic therapy could be reasonably considered as
      first line. In most situations, however, treatment with PTH follows a course of
      antiresorptive therapy. Simultaneous combination therapy with PTH and an
      antiresorptive drug does not appear to provide any advantages over monotherapy.
      After the recommended 2-year period of PTH treatment, an antiresorptive should be
      used to maintain densitometric gains. The drugs are well tolerated. Early safety
      concerns about osteosarcoma in rats have not been borne out after almost 9 years
      experience with human subjects.

PMID- 21740289
TI  - Adherence and persistence to a regimen of basal insulin in a pre-filled pen
      compared to vial/syringe in insulin-naive patients with type 2 diabetes.
AB  - OBJECTIVE: This study was conducted to compare adherence and persistence of
      patients initiating basal insulin therapy with Levemir FlexPen versus those
      initiating basal insulin therapy with NPH via vial and syringe. MATERIALS AND
      METHODS: Data were gathered from a large US retrospective claims database, and
      included patients with type 2 diabetes that initiated basal insulin therapy with
      either Levemir FlexPen or NPH in vials. Patients were defined as adherent to
      therapy if they had a medication possession ratio (MPR) of >=80% in the 12-month
      follow-up period and were defined as persistent with therapy if they had no gaps
      in insulin therapy in the follow-up period. RESULTS: After controlling for
      confounders using logistic regression, patients initiating therapy with Levemir
      FlexPen had 39% higher adjusted odds of achieving an MPR >=80% versus patients
      initiating therapy with NPH vial (OR 1.39; 95% CI: 1.04-1.85). Analysis of
      persistence using a Cox proportional hazards model indicated that patients
      initiating Levemir FlexPen had a 38% lower hazard of discontinuation compared to
      NPH vial (HR 0.62, 95% CI: 0.55-0.70). LIMITATIONS: Claims-based studies are
      limited to the extent that they accurately capture medical and pharmacy use.
      Also, relying on claims-based data limits the generalizability of the findings to
      similar populations and treatments. CONCLUSIONS: These results suggest that
      persistence and adherence with insulin may be improved for patients initiating
      basal insulin therapy with Levemir FlexPen versus NPH vial.

PMID- 21740291
TI  - Cost-effectiveness of risk stratification for preventing type 2 diabetes using a
      multi-marker diabetes risk score.
AB  - BACKGROUND: Personalized medicine requires diagnostic tests that stratify
      patients into distinct groups that may differentially benefit from targeted
      treatment approaches. This study compared the costs and benefits of two
      approaches for identifying those at high risk of developing type 2 diabetes for
      entry into a diabetes prevention program. The first approach identified high risk
      patients using impaired fasting glucose (IFG). The second approach used the PreDx
      Diabetes Risk Score (DRS) to further stratify IFG patients into high-risk and
      moderate-risk groups. METHODS: A Markov model was developed to simulate the
      incidence and disease progression of diabetes and consequent costs and quality
      adjusted life expectancy (QALY), comparing alternative approaches for identifying
      high-risk patients. We modeled direct medical costs, including the costs of the
      stratification testing, over a 10-year time horizon from a US payer perspective.
      RESULTS: Stratification of IFG patients by the DRS method leads to improved
      identification and prevention among those at highest risk. At 5 years, the number
      needed to treat (NNT) in the IFG-only approach was 39 patients to prevent one
      case of diabetes compared to an NNT of 15 in the IFG + DRS approach. When
      compared to IFG alone, the IFG + DRS approach results in an incremental cost
      effectiveness ratio (ICER) of $17,100/QALY gained at 5 years and would become
      cost saving in 10 years. In contrast and as compared to no stratification, the
      IFG-only approach would produce an ICER of $235,500/QALY gained at 5 years and
      $94,600/QALY gained at 10 years. The study findings are limited by the
      generalizability of the DRS validation study and uncertainty regarding the long
      term effectiveness of diabetes prevention. CONCLUSIONS: The analysis indicates
      that the cost-effectiveness of diabetes prevention can be improved by better
      identification of patients at highest risk for diabetes using the DRS.

PMID- 21740292
TI  - Targeting voltage-gated calcium channels for the treatment of neuropathic pain: a
      review of drug development.
AB  - INTRODUCTION: Pain is a major burden for affected individuals and society, and
      controlling neuropathic pain is especially challenging. The number of drugs
      available is limited and treatments are often marginally effective and burdened
      by side effects. Voltage-gated calcium channels (VGCC) play a major role in the
      development and maintenance of neuropathic pain and are thus prime targets for
      its treatment. AREAS COVERED: Currently available drugs that target the calcium
      channel include ziconotide, gabapentin and pregabalin. While there are no VGCC
      blockers currently in clinical trials, there are many in development. Recently,
      orally available, use-dependent compounds have been reported. We will review, in
      detail, compounds currently in development and include a brief review of VGCC and
      the drugs currently in use. EXPERT OPINION: There is real hope that new drugs
      targeting calcium channels will soon be available. This hope is based on
      advancing technologies for peptide synthesis, more efficient drug screening and
      orally available, use-dependent compounds. Some form of direct VGCC blockade or
      modulation will always have a place in the treatment of neuropathic pain, but
      given the complexity and neuroplasticity of pain transmission, polypharmacy will
      likely be required for many chronic pain sufferers for the foreseeable future.

PMID- 21740293
TI  - Development of c-MET pathway inhibitors.
AB  - INTRODUCTION: The aberrantly upregulated c-mesenchymal-epithelia transition
      factor (c-MET) signaling pathway has been considered to be an attractive target
      for cancer intervention owing to the important roles it plays in tumor formation,
      progression, metastasis, angiogenesis and drug resistance. Based on the
      historical preclinical evidence, a number of c-MET pathway targeted agents are
      being developed in the clinic, and recent clinical data have begun to provide
      some insight into which tumor types and patient populations a c-MET pathway
      inhibitor may be beneficial for. AREAS COVERED: Through reviewing recent
      publications in the literature and information disclosed in other public forums,
      we describe the current understanding of c-MET biology in human malignancies and
      discuss the latest progress in the development of c-MET pathway inhibitors for
      cancer treatment. EXPERT OPINION: The c-MET pathway inhibitors currently being
      evaluated in the clinic have demonstrated compelling evidence of clinical
      activity in different cancer types and may provide significant therapeutic
      opportunities. The challenges, however, are to identify the tumor types and
      patient populations that benefit most, and find the most effective combinations
      of therapies while minimizing potential toxicity.

PMID- 21740294
TI  - Enhancement of the anti-tumor activity of therapeutic monoclonal antibodies by
      CXCR4 antagonists.
AB  - The interaction between CXCR4 on the surface of tumor cells and CXCL12 in the
      stroma is believed to contribute to tumor cell survival and protection against
      drug treatment. Inhibition of stromal survival signals by CXCR4 antagonists has
      been reported to render tumor cells more sensitive to chemotherapy, but little is
      known about potential synergy with monoclonal antibodies. In this study,
      administration of the small molecule CXCR4 antagonists plerixafor and GENZ-644494
      was found to enhance the anti-tumor activity of the monoclonal antibodies
      alemtuzumab and rituximab in disseminated lymphoma models. The observed
      enhancement in therapeutic efficacy by CXCR4 antagonists appeared to involve
      several factors, including interference with the tumor-promoting signals
      delivered by CXCL12, disruption of the tumor/stroma interaction and mobilization
      of effector neutrophils capable of mediating antibody-dependent cell-mediated
      cytotoxicity. The involvement of neutrophils was further supported by the
      observed reversal in therapeutic benefit upon neutrophil depletion.

PMID- 21740295
TI  - Reducing neurotoxicity in the management of multiple myeloma.

PMID- 21740296
TI  - Morphological, immunophenotypic and molecular characterization of mature
      aggressive B-cell lymphomas in Chinese pediatric patients.
AB  - Differential diagnosis of Burkitt lymphoma (BL), diffuse large B-cell lymphoma
      (DLBCL) and B cell lymphoma, unclassifiable, with features intermediate between
      BL and DLBCL (intermediate BL/DLBCL) can be difficult. We studied 97 Chinese
      pediatric mature aggressive B-cell lymphomas including 81 BL cases, eight DLBCL
      cases and eight intermediate BL/DLBCL cases using immunohistochemistry,
      interphase fluorescence in situ hybridization (FISH) and Epstein-Barr virus (EBV)
      in situ hybridization. Our results showed that there were no significant
      differences in the expression of CD10 and BCL6 among cases of BL (91% and 86%,
      respectively), DLBCL (75% and 63%, respectively) and intermediate BL/DLBCL (75%
      and 63%, respectively) (p > 0.05). The expression of BCL2 (3% in BL, 50% in
      DLBCL, 50% in intermediate BL/DLBCL), expression of MUM1 (17% in BL, 63% in
      DLBCL, 63% in intermediate BL/DLBCL) and mean Ki-67 proliferation index (PI) (93%
      in BL, 83% in DLBCL, 80% in intermediate BL/DLBCL) were significantly different
      between BL and DLBCL and between BL and intermediate BL/DLBCL. The frequency of
      an extra copy of BCL6 (0% in BL, 37.5% in DLBCL, 25% in intermediate BL/DLBCL)
      and EBV-encoded RNA (EBER) positivity (48% in BL, 0% in DLBCL and intermediate
      BL/DLBCL) were also significantly different between BL and DLBCL and between BL
      and intermediate BL/DLBCL. The frequency of C-MYC rearrangement in BL (98%) was
      much higher than in DLBCL (37.5%) and intermediate BL/DLBCL (50%). Our findings
      suggest that diagnosis of the mature aggressive B-cell lymphomas in pediatrics
      should be based on the comprehensive review and integration of morphological,
      immunohistochemical and molecular genetic features. The expression of CD10 and
      BCL6 but not BCL2, a high Ki-67 PI (>90%) and a C-MYC rearrangement but not BCL2
      or BCL6 rearrangement are the features of BL. MUM1 is not an exclusionary
      diagnostic marker for BL. As the immunophenotype and molecular genetic features
      of DLBCL and intermediate BL/DLBCL are similar, intermediate BL/DLBCL is more
      likely a subgroup of DLBCL in the pediatric population. Regardless of the
      expression of CD10 and BCL6, strong staining for BCL2, Ki-67 PI below 90% and the
      presence of extra copies of BCL6 favor a diagnosis of DLBCL or intermediate
      BL/DLBCL.

PMID- 21740297
TI  - Treatment of Hodgkin lymphoma with adriamycin, bleomycin, vinblastine and
      dacarbazine without routine granulocyte-colony stimulating factor support does
      not increase the risk of febrile neutropenia: a prospective cohort study.
AB  - Although patients with Hodgkin lymphoma treated with adriamycin, bleomycin,
      vinblastine and dacarbazine (ABVD) chemotherapy frequently develop neutropenia,
      febrile neutropenia is uncommon. Three retrospective trials reported that ABVD
      could be safely administered without dose delays or granulocyte-colony
      stimulating factor (G-CSF) support. We retrospectively reviewed the charts of 89
      patients treated with ABVD and found that the incidence of febrile neutropenia
      was 0.5% (five of 927 treatments). This prompted a change to our institutional
      policy so that patients receiving ABVD no longer receive routine G-CSF for
      uncomplicated neutropenia. We then prospectively assessed the safety of this
      policy change. Thirty-three patients received a total of 327 ABVD treatments, 185
      (57%) of which were administered with a neutrophil count <1.5 * 10(9)/L. Febrile
      neutropenia occurred in 2/33 patients (6%), complicating 0.6% of chemotherapy
      treatments (2/327). Eliminating routine G-CSF saved $10 241 per patient. Omission
      of G-CSF for uncomplicated neutropenic patients receiving ABVD for Hodgkin
      lymphoma is cost-saving and safe.

PMID- 21740298
TI  - Management of gram-positive bacterial infections in patients with cancer.
AB  - Bacterial infections, particularly those due to gram-positive bacteria, continue
      to predominate in patients with cancer. Coagulase-negative and coagulase-positive
      staphylococci and enterococci remain as common pathogenic microorganisms.
      Clostridium difficile has emerged as a significant pathogen. Major clinical
      syndromes include vascular catheter-related infection, febrile neutropenia,
      diarrhea and colitis. Rising antimicrobial resistance among gram-positive
      bacteria is of serious concern. The clinical utility of penicillin against
      streptococci and vancomycin against coagulase-negative and coagulase-positive
      staphylococci and enterococci may be rapidly diminishing. Liberal empiric use of
      vancomycin during neutropenic fever needs careful reconsideration. Newer
      promising anti-gram-positive bacterial drugs with activity against methicillin
      resistant staphylococci include daptomycin, linezolid, tigecycline and
      telavancin. However, toxicity concerns, limited data in immunocompromised
      populations and high cost prevent the widespread use of these drugs among
      patients with cancer.

PMID- 21740299
TI  - Allogeneic stem cell transplantation in therapy-related acute myeloid leukemia
      and myelodysplastic syndromes: impact of patient characteristics and timing of
      transplant.
AB  - Patients with therapy-related acute myeloid leukemia (t-AML) and myelodysplastic
      syndromes (t-MDS) have poor survival and high non-relapse mortality (NRM) after
      allogeneic stem cell transplantation. This retrospective study assessed the
      transplant outcomes of 29 consecutive patients with t-AML (83%) or t-MDS (17%)
      treated with allogeneic transplantation. The median age of patients was 51 years.
      Donors were mostly matched unrelated (52%), and 59% of patients received
      myeloablative conditioning. Two-year overall survival, event-free survival and
      relapse incidence were 37%, 34% and 33%; NRM was 17% at 100 days, and 32% at 2
      years. Event-free survival was reduced in patients with high-risk cytogenetics (p
      = 0.02), Karnofsky performance status <= 80% (p = 0.001) and disease after
      induction +/- consolidation (p = 0.006). NRM was higher in patients receiving > 2
      therapy lines for previous cancer (p = 0.01) and in those allografted > 6 months
      from diagnosis (p = 0.03). In conclusion, allogeneic transplantation should be
      proposed timely to these patients after an accurate analysis of patient history.

PMID- 21740300
TI  - Role of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in early and
      late therapy assessment of patients with advanced Hodgkin lymphoma treated with
      bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and
      prednisone.
AB  - The prognostic value of positron emission tomography (PET) in early therapy
      response assessment, after completion of chemotherapy and 3 months after the end
      of treatment in advanced Hodgkin lymphoma (HL) remains to be defined. We report
      the results of 69 patients with first presentation of advanced HL. [18F]-fluoro-2
      deoxy-d-glucose (FDG)-PET scan was performed after four cycles (PET-4), on
      completion of chemotherapy after 6/8 cycles (PET-6/8) and 3 months after the
      completion of chemotherapy (PET 3-months). Median follow-up was 55 months. The
      negative predictive value (NPV) for PET-4, PET-6/8 and PET 3-months was 98%, 95%
      and 97%, respectively. The 4-year progression-free survival (PFS) for PET-4
      negative (n = 51) and PET-4 positive (n = 18) patients was 96% and 78%,
      respectively (p = 0.016). The 4-year PFS for PET-6/8 negative (n = 59) and PET
      6/8 positive (n = 9) patients was 95% and 78%, respectively (p = 0.046). Patients
      with a large mediastinal mass constituted nearly all of the PET-4 positive
      (16/18) and PET-6/8 positive (8/9) patients. After radiotherapy of PET-6/8
      positive patients, PET 3-months was negative in 64 (97%) and positive in two (3%)
      patients. PET 3-months after the end of chemotherapy was of limited value when
      the interim PET-4 was negative. Interim PET after four cycles of bleomycin,
      etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone
      (BEACOPP) is a strong prognostic marker for PFS in advanced HL.

PMID- 21740301
TI  - Intrapleural rituximab for the treatment of malignant pleural effusion due to B
      cell lymphomas.

PMID- 21740302
TI  - Cytoreduction with gemtuzumab ozogamicin and cytarabine prior to allogeneic stem
      cell transplant for relapsed/refractory acute myeloid leukemia.

PMID- 21740303
TI  - Interferon regulatory factor-1 binds c-Cbl, enhances mitogen activated protein
      kinase signaling and promotes retinoic acid-induced differentiation of HL-60
      human myelo-monoblastic leukemia cells.
AB  - All-trans retinoic acid (RA) and interferons (IFNs) have efficacy in treating
      certain leukemias and lymphomas, respectively, motivating interest in their
      mechanism of action to improve therapy. Both RA and IFNs induce interferon
      regulatory factor-1 (IRF-1). We find that in HL-60 myeloblastic leukemia cells
      which undergo mitogen activated protien kinase (MAPK)-dependent myeloid
      differentiation in response to RA, IRF-1 propels differentiation. RA induces MAPK
      dependent expression of IRF-1. IRF-1 binds c-Cbl, a MAPK related adaptor. Ectopic
      IRF-1 expression causes CD38 expression and activation of the Raf/MEK/ERK axis,
      and enhances RA-induced differentiation by augmenting CD38, CD11b, respiratory
      burst and G0 arrest. Ectopic IRF-1 expression also decreases the activity of
      aldehyde dehydrogenase 1, a stem cell marker, and enhances RA-induced ALDH1 down
      regulation. Interestingly, expression of aryl hydrocarbon receptor (AhR), which
      is RA-induced and known to down-regulate Oct4 and drive RA-induced
      differentiation, also enhances IRF-1 expression. The data are consistent with a
      model whereby IRF-1 acts downstream of RA and AhR to enhance Raf/MEK/ERK
      activation and propel differentiation.

PMID- 21740304
TI  - B cell homeostasis and the development of chronic graft-versus-host disease:
      implications for B cell-depleting therapy.
AB  - Chronic graft-versus-host disease (GVHD) is a serious complication that develops
      frequently in survivors of allogeneic stem cell transplant. Since elucidation of
      the role of B cells in the pathogenesis of chronic GVHD, B cell-depleting therapy
      with rituximab has been associated with beneficial effects in clinical and
      laboratory studies in patients with chronic GVHD. Although the mechanism
      underlying the contribution of B cells to the development of chronic GVHD is
      poorly understood, recent studies have proposed that B cell reconstitution after
      allogeneic stem cell transplant is involved in the development of chronic GVHD.
      Inadequate reconstitution of naive B cells and the persistence of high levels of
      B cell-activating factor have been found in patients with chronic GVHD, and these
      changes might be associated with the expansion of activated CD27-positive B cells
      that produce autoantibody in chronic GVHD. In the light of this altered B cell
      homeostasis in chronic GVHD, the role of rituximab in controlling the clinical
      manifestations of chronic GVHD has been studied. In this review, we address the
      role of B cells in the pathogenesis of chronic GVHD and the response to B cell
      depleting therapy based on B cell homeostasis.

PMID- 21740305
TI  - Reduction of transforming growth factor-beta1 expression in leukemia and its
      possible role in leukemia development.
AB  - The expression of transforming growth factor-beta1 (TGF-beta1) in leukemic cells
      and sera from patients with leukemia and its possible role in leukemia
      development were studied. TGF-beta1 levels in culture supernatants from leukemic
      cells were significantly lower than those from normal bone marrow mononuclear
      cells. Serum TGF-beta1 levels in leukemic patients were significantly lower
      compared with healthy controls, but returned to normal in patients achieving
      complete remission, and decreased when patients relapsed. TGF-beta1 mRNA
      expression levels were significantly higher in normal bone marrow mononuclear
      cells but lower in leukemic cells compared with normal CD34 + cells. After
      transfection of the TGF-beta1 gene to HL-60 cells, cell apoptosis was detected.
      Moreover, by flow cytometry analysis, cells arrested in G1 phase were 62% for TGF
      beta1 transfected cells and 44% for controls. Transfection of exogenous TGF-beta1
      gene inhibited HL60 cells xenograft growth in nude mice, and prolonged survival
      of tumor-bearing mice compared with the controls. Decreased endogenous TGF-beta1
      expression in leukemia cells may be involved in leukemia development,
      Transfection of exogenous TGF-B1 gene to HL60 can inhibit the proliferation of
      the cells and induce cell apoptosis by down regulating bcl-2, hTERT (human
      telomerase reverse transcriptase) and c-myc expression.

PMID- 21740306
TI  - Association between non-Hodgkin lymphoma and renal cell carcinoma.
AB  - The incidence of patients with multiple primary tumors has been increasing in
      recent years. The association between non-Hodgkin lymphomas (NHL) and renal cell
      carcinoma (RCC) is unclear. The presentation of 10 patients with co-existent NHL
      and RCC at our institution in the past 3 years led us to explore whether this was
      a chance association or a statistically significant phenomenon. We used the US
      Surveillance, Epidemiology and End Results (SEER) program (www.seer.cancer.gov)
      from 1973 to 2006 to identify a total of 892 445 537 subjects aged 18-84, with
      known values for race and gender at risk for NHL and RCC. Among these, 181 009
      were diagnosed with NHL, 118 122 were diagnosed with RCC and 1039 had both NHL
      and RCC. This was significantly higher than the expected number of 24 with co
      existent NHL and RCC (p < 0.0001). The observed number (O) of RCC after NHL was
      significantly higher than the expected number (E) (O/E: 1.51; 95% confidence
      interval [CI] 1.36-1.66), with the O/E ratio remaining elevated across the
      various follow-up time intervals. The observed number of NHL after RCC was not
      significantly different from the expected number (O/E: 1.09; 95% CI 0.98-1.22).
      In univariate analyses, race and gender were significantly associated with an
      increased cumulative incidence of RCC after NHL. Multivariate analysis with age,
      race and gender revealed that white males had a higher cumulative incidence of
      RCC after NHL. These findings suggest that patients with NHL are at increased
      risk for RCC.

PMID- 21740307
TI  - Postural sway in patients with mild to moderate Parkinson's disease.
AB  - Clinical assessment of postural instability in persons with Parkinson's disease
      (PD) is done with the retropulsive pull test, but since this test does not assess
      the underlying causes of postural instability, there is a need for additional
      assessment tools. The aim of this study was to identify postural sway parameters
      for use in a multifactorial approach to quantify postural instability. Nineteen
      adults diagnosed with idiopathic PD, 14 healthy age-matched controls (EH), and 10
      healthy young adults (YH) completed the study. Postural parameters were extracted
      during quiet standing in eyes open (EO) and eyes closed (EC) conditions. Removing
      visual feedback affected the groups in a similar way. Significant differences
      between the PD and the two control groups were found in sway path length, area,
      and ranges in the anterior-posterior (AP) and medial-lateral (ML) directions and
      the Hurst exponents. PD significantly increased AP sway path length compared with
      YH and ML sway path length compared with EH. The Hurst exponents in PD were
      significantly different than in EH. The results suggest that the ML direction is
      a successful discriminator between PD and age-matched controls and that the
      interaction between ML and AP directions should be considered in the method used
      to quantify postural instability.

PMID- 21740308
TI  - Pilot trial of onabotulinumtoxina (Botox) in moderate to severe restless legs
      syndrome.
AB  - OBJECTIVE: To evaluate the potential of onabotulinum toxin A (Botox(r), Allergan,
      Inc., Irvine, California) in the treatment of restless legs syndrome (RLS).
      METHODS: A single-arm, open-label pilot trial of onabotulinum toxin A was
      conducted to determine its usefulness as an injectable treatment for RLS.
      RESULTS: The primary outcome measure, change in score on the International
      Restless Legs Syndrome Scale, showed a statistically significant improvement in
      RLS during the first 4 weeks after treatment. Two of the secondary outcome
      measures, pain (measured using a visual analog scale) and patients' global
      impression of severity of illness also showed improvement. CONCLUSIONS:
      Onabotulinum toxin A warrants further study in RLS. Increasing the drug dosage,
      changing the dosing schedule, and increasing the number of injection sites may
      result in greater activity and longer duration of action.

PMID- 21740309
TI  - Localized cysteine sulfenic acid formation by vascular endothelial growth factor:
      role in endothelial cell migration and angiogenesis.
AB  - Reactive oxygen species (ROS) are important mediators for VEGF receptor 2
      (VEGFR2) signalling involved in angiogenesis. The initial product of Cys
      oxidation, cysteine sulfenic acid (Cys-OH), is a key intermediate in redox signal
      transduction; however, its role in VEGF signalling is unknown. We have previously
      demonstrated IQGAP1 as a VEGFR2 binding scaffold protein involved in ROS
      dependent EC migration and post-ischemic angiogenesis. Using a biotin-labelled
      Cys-OH trapping reagent, we show that VEGF increases protein-Cys-OH formation at
      the lamellipodial leading edge where it co-localizes with NADPH oxidase and
      IQGAP1 in migrating ECs, which is prevented by IQGAP1 siRNA or trapping of Cys-OH
      with dimedone. VEGF increases IQGAP1-Cys-OH formation, which is prevented by N
      acetyl cysteine or dimedone, which inhibits VEGF-induced EC migration and
      capillary network formation. In vivo, hindlimb ischemia in mice increases Cys-OH
      formation in small vessels and IQGAP1 in ischemic tissues. In summary, VEGF
      stimulates localized formation of Cys-OH-IQGAP1 at the leading edge, thereby
      promoting directional EC migration, which may contribute to post-natal
      angiogenesis in vivo. Thus, targeting Cys-oxidized proteins at specific
      compartments may be the potential therapeutic strategy for various angiogenesis
      dependent diseases.

PMID- 21740310
TI  - Role of reactive oxygen species in the early stages of liver regeneration in
      streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is a risk factor for prognosis after liver resection. In
      previous work, we found a pro-apoptotic state in the diabetic rat liver. In this
      work, this was also observed 1 hour post-partial hepatectomy (PH) and resulted in
      a deficient regenerative response 24 hours post-PH. Treatment with insulin and/or
      Desferoxamine (DES) (iron chelator) or Tempol (TEM) (free radicals scavenger) was
      effective in preventing the liver reactive oxygen species (ROS) production
      induced by diabetic state. High levels of ROS play a role in hepatic lipid
      peroxidation in diabetes before and after PH, and lead to increased pro-apoptotic
      events, which contribute to a reduced regenerative response. This becomes of
      relevance for the potential use of antioxidants/free radical scavengers plus
      insulin for improvement of post-surgical recovery of diabetic patients subjected
      to a PH.

PMID- 21740311
TI  - Advanced oxidation protein products (AOPP): novel uremic toxins, or components of
      the non-enzymatic antioxidant system of the plasma proteome?
AB  - In 1996, a novel oxidative stress biomarker, referred to as advanced oxidation
      protein products (AOPP), was detected in the plasma of chronic uremic patients.
      It was suggested that AOPP measure highly oxidized proteins, especially albumin.
      Recent data in turn appear to indicate that oxidized fibrinogen is the key
      molecule responsible for the AOPP reaction in the human plasma. Since fibrinogen
      is an acute-phase reactant, it is evident that during each episode of
      inflammatory response, the antioxidant capacity of the plasma is enhanced. In
      this context, fibrinogen can be regarded as a component of the antioxidant system
      of the plasma proteome. It was also demonstrated that oxidized fibrinogen is
      bound to apolipoprotein(a) of lipoprotein(a) via lysine binding sites. Thus,
      apo(a) could compete with plasminogen (and/or tissue plasminogen activator) for
      its binding sites of fibrin(ogen), causing inhibition of fibrinolysis, and
      thereby promote atherosclerosis and cardiovascular disease.

PMID- 21740312
TI  - Soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein
      (LBP) in neonatal sepsis: new clinical and analytical perspectives for two old
      biomarkers.
AB  - Several biochemical markers have been proposed over the past years to manage
      critically ill newborns with acute inflammation and sepsis. The state of the art
      in diagnosing and monitoring neonatal sepsis, severe sepsis and septic shock
      consists of the measurement of plasma C-reactive protein (CRP) and procalcitonin
      (PCT) at the onset and in the course of the disease. CRP and PCT in combination
      are clinically significant in diagnosing and monitoring septic newborns; however,
      CRP and PCT have a very limited value for risk stratification and in predicting
      outcome. The availability of commercial methods for the automated measurement of
      the soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding
      protein (LBP) represent a challenge for the evaluation in clinical practice of
      reliable markers of neonatal sepsis, specifically for the very early diagnosis,
      the classification into class of severity, and the prediction of complications
      and death.

PMID- 21740313
TI  - Minimally invasive perinatal autopsies using magnetic resonance imaging and
      endoscopic postmortem examination ("keyhole autopsy"): feasibility and initial
      experience.
AB  - OBJECTIVE: Perinatal autopsy provides additional diagnostic information in a
      significant proportion of cases but parents and relatives frequently decline
      traditional postmortem (PM) examination, partly due to the unacceptability of the
      cosmetic effects of large incisions and concerns regarding organ retention. We
      present a novel minimally invasive autopsy method for fetal and neonatal
      PMexaminations, which includes PM magnetic resonance imaging (MRI) for assessment
      of anatomy and endoscopic internal examination to allow direct organ
      visualization and targeted tissue biopsy. METHODS: Descriptive retrospective
      feasibility report of the first 10 perinatal cases undergoing endoscopic
      minimally invasive autopsy. RESULTS: A minimally invasive autopsy (MIA) approach
      based on postmortem MRI (PM MRI) and endoscopic autopsy with tissue biopsy is
      feasible and effective with minimal cosmetic consequences compared to traditional
      PM examination. Endoscopic examination with tissue biopsy provided additional
      diagnostic information to PM MRI alone in the majority of cases. CONCLUSIONS:
      Endoscopic MIA is a feasible and potentially more acceptable approach to
      perinatal autopsy and provides an additional option for parents who do not agree
      to a traditional PM examination. This approach could result in increased
      utilization of investigations after death in this group of patients.

PMID- 21740314
TI  - Analysis of the original causes of placental oxidative stress in normal pregnancy
      and pre-eclampsia: a hypothesis.
AB  - Pre-eclampsia (PE) and eclampsia remain enigmatic despite intensive research.
      Growing evidence suggests that placental oxidative stress (OS) is involved in the
      etiopathogenesis of pre-eclampsia. Reduced perfusion as a result of abnormal
      placentation was proposed to be responsible for placental OS in PE. However,
      placental OS was also observed in normal pregnancy. The exact differences and
      correlation of placental OS in PE and normal pregnancy remain elusive. In this
      review, we attempted to link both normal pregnancy and PE on the causes of
      placental OS and proposed a hypothesis that placental OS in normal pregnancy,
      plus the exploration of other placental and/or maternal factors, could provide a
      novel explanation of that in PE. We concluded that pregnancy, placental
      abnormality and preexisting maternal constitutional conditions are three
      principle factors that could contribute to placental OS in PE. The specific
      causes in each clinical case could be heterogeneous, which requires individual
      analysis.

PMID- 21740315
TI  - New onset delayed postpartum preeclampsia: different disorders?
AB  - OBJECTIVE: Delayed postpartum preeclampsia is a poorly studied disorder. We
      compared new onset delayed postpartum preeclampsia (NOPP) to
      recurrent/persistent, delayed onset postpartum preeclampsia (RPP) to see whether
      these were different disorders. METHODS: Delayed onset preeclampsia was defined
      as readmission >2 days to <= 6 weeks postpartum for preeclampsia. The NOPP group
      had no antecedent diagnosis of hypertensive disorders in the current pregnancy,
      and was compared to the RPP defined as a prior hypertensive disorder in the
      current pregnancy in terms of maternal demographics, obstetric and medical
      history, intrapartum and early postpartum course and clinical signs and symptoms
      and outcomes on postpartum readmission. RESULTS: There were a total of 56 (36.8%)
      patients in the RPP and 96 (63.2%) patients in the NOPP groups. NOPP cases
      delivered significantly later 39.0 +/- 2 weeks vs. 37 +/- 3.0 weeks p < 0.001,
      and had significantly lower blood pressure during the antepartum, early
      postpartum and readmission periods. In addition the NOPP group had significantly
      higher average number of symptoms 2 vs. 1.5 p = 0.013 on postpartum readmission.
      There were no statistically significant differences in the rates of major
      complications. CONCLUSIONS: In this comprehensive study of delayed postpartum
      preeclampsia, there were few significant differences in the clinical course and
      no differences in complications in the NOPP subgroup compared to cases with
      preeclampsia recurring in the late postpartum period.

PMID- 21740316
TI  - Implications of maternal systemic oxidative stress in normal pregnancy and in
      pregnancy complicated by preeclampsia.
AB  - OBJECTIVES: To evaluate the intensity of oxidative stress in normal pregnancy and
      in pregnancy complicated by preeclampsia. To investigate a possible correlation
      between the intensity of oxidative stress, severity of preeclampsia and the fetal
      status at birth. MATERIALS AND METHODS: A retrospective transversal study was
      performed in three groups of 80 patients each: Group I--preeclampsia; Group II-
      normal pregnancy; Group III--control (non-pregnant patients). Degradation
      products of reactive oxygen species (lipid peroxides and protein carbonyls) and
      some antioxidants (hydrogen donor capacity and ceruloplasmin) were determined in
      the serum of patients. The data obtained were processed by descriptive and
      comparative statistical methods. RESULTS: A moderate level of oxidative stress
      was found in normal pregnancy. We found statistically significant differences
      between the control group and the normal pregnancy group (p < 0.000). In
      preeclampsia, oxidative stress increases. Statistically significant differences
      were found in the evaluated parameters between the normal pregnancy group and the
      preeclampsia group (p < 0.000). There were no correlations between the intensity
      of oxidative stress, severity of preeclampsia and the fetal status at birth in
      the group with preeclampsia. CONCLUSION: Oxidative stress in preeclampsia is the
      result of the increase in reactive oxygen species and of the decrease in
      antioxidants.

PMID- 21740317
TI  - The influence of planned kinds of delivery on pregnant women's emotional state.
AB  - OBJECTIVE: To evaluate if labour induction and elective caesarean section could
      influence anxiety and depression in pregnant women. METHODS: One hundred and
      sixteen consecutive pregnant women with uncomplicated singleton pregnancy at
      term, scheduled for these two obstetric procedures were enrolled. An anonymous
      questionnaire with two self-rating instruments STAI and HAM-A for anxiety and HAM
      D for depression was administered. RESULTS: Anxiety levels did not show
      significant differences while a light depressive mood was evidenced among
      pregnant women waiting for labour induction (p = 0.01). CONCLUSIONS: An adequate
      psychological support could be considered a helpful tool for pregnant women
      scheduled for labour induction.

PMID- 21740318
TI  - Suspected versus non-suspected small-for-gestational age fetuses at term:
      perinatal outcomes.
AB  - OBJECTIVE: To compare perinatal outcomes of suspected versus non-suspected small
      for-gestational age fetuses (SGA) at term. METHODS: Retrospective cohort study
      among all term singleton neonates with a birth weight <10th percentile born in
      the Parkstad region between 1 January 2006 and 3 March 2008. The subjects were
      assigned to a prenatally suspected or non-suspected SGA group. Primary outcome
      was adverse neonatal outcome at birth, defined as a composite of intrauterine
      fetal death, Apgar <7 at 5 min, or pH umbilical artery <7.05. Secondary outcome
      included neonatal medium care unit (NMCU) admission >= 7 days. RESULTS: 430
      subjects were included in the study; 36.7% was suspected of SGA. In the suspected
      SGA group mean gestational age at birth and birth weight were significantly
      lower, whereas maternal morbidity was significantly higher. The incidence of
      labor induction and elective cesarean section were also significantly higher in
      the suspected SGA group. Total perinatal mortality was 2.1%. Identification of
      SGA and subsequent management led to a significant decrease of adverse neonatal
      outcome at birth, but did not lead to a significant decrease in NMCU admission >=
      7 days. CONCLUSIONS: Suspicion of SGA was associated with a more active
      management of labor and delivery, resulting in a better neonatal outcome at
      birth.

PMID- 21740319
TI  - Maternal and neonatal immediate effects of sequential delivery.
AB  - OBJECTIVE: To evaluate the immediate maternal and neonatal outcomes associated
      with sequential instrumental delivery (vacuum plus forceps) compared with the use
      of one instrument only (forceps or vacuum). STUDY DESIGN: A longitudinal
      observational study was carried out, including all instrumental deliveries
      performed in term singleton pregnancies, in vertex presentation, at station level
      0 or +1. According to the type of the instruments, the deliveries were divided in
      three groups: the vacuum group, the forceps group and the sequential group.
      Immediate maternal and neonatal outcomes were evaluated. RESULTS: A total of 275
      instrumental deliveries were performed: 126 (45.5%) vacuum assisted deliveries,
      62 (22.6%) forceps assisted deliveries and 87 (31.6%) sequential deliveries.
      Regarding maternal morbidity, there was a significant difference between the
      three groups (p < 0.001), with a higher rate of complications in the sequential
      group. The type of instrument was the only factor associated with significant
      maternal morbidity. The rate of immediate neonatal morbidity was 4.4% and there
      was no significant association with the instrument type or with other
      identifiable factors. CONCLUSION: Sequential delivery is associated with a higher
      maternal morbidity and it seems not to increase neonatal morbidity.

PMID- 21740320
TI  - Impact of maternal fasting during Ramadan on fetal Doppler parameters, maternal
      lipid levels and neonatal outcomes.
AB  - OBJECTIVE: The aim of the present study was to evaluate whether fasting may cause
      changes in maternal lipid profile, glucose level and ketonuria, and whether it
      has any adverse effects on fetal Doppler, birthweight, preterm delivery or
      cesarean section rate. METHODS: Fifty-six consecutive, healthy women with
      singleton uncomplicated pregnancies of >= 28 week gestation who had fasted for at
      least 10 consecutive days during the study period were defined as the study
      group. Fifty-four healthy non-fasted women matched for age, parity, and
      gestational age were defined as the control group. Groups were compared according
      to fetal middle cerebral artery and umbilical artery systolic/diastolic ratio,
      maternal serum lipid levels and neonatal outcomes (gestational age at delivery,
      birthweight, delivery type and neonatal intensive care admission). RESULTS: No
      statistical difference was found between the groups according to fetal Doppler
      parameters, amniotic fluid index, gestational age at delivery, cesarean section
      rate, birthweight or NICU admission. However, lower levels of VLDL, triglyceride
      and higher incidence of ketonuria were detected in the fasting group (p < 0.05).
      CONCLUSION: Fasting of healthy women during pregnancy seems to have no adverse
      effects on amniotic fluid index, fetal Doppler and delivery parameters.

PMID- 21740321
TI  - First trimester serum markers stability during sample transportation from the
      obstetrical site to the screening laboratory.
AB  - OBJECTIVE: To investigate the effect of temperature on first trimester free beta
      hCG and PAPP-A in serum during transportation. METHODS: Maternal blood was
      collected from 30 East Asian women attending for Down syndrome screening at the
      primary obstetrical site. The extracted serum was split into two equal aliquots,
      placed in identical thermally insulated pouches with a temperature data logger
      and shipped to the screening laboratory. An 800 g frozen ice pack was placed in
      one of the pouches. Free beta-hCG and PAPP-A levels were determined in the
      'Cooled' and 'Uncooled' serum samples using a DELFIA((r)) Xpress analyzer. The
      proportion of 'Uncooled' samples not within 5% of the 'Cooled' sample marker
      level was assessed. RESULTS: The median age of subjects was 36 years, half were
      nulliparous and all were non-smokers. The assay stability ranged from 2.38% to
      4.41%. The median total transport time from the obstetrical site to the
      laboratory was 17.37 h. Median recorded temperatures within the 'Cooled' pouch
      were significantly lower throughout the transportation of the samples (p <
      0.0001). The median percentage change of free beta-hCG and PAPP-A concentrations
      in 'Uncooled' samples relative to 'Cooled' samples were 2.72% (range 0.27-7.64%)
      and 1.10% (range 0.03%-4.29%), respectively. Free beta-hCG concentrations
      differed by greater than 5% in eleven (37%) subjects. CONCLUSIONS: Insulated
      packaging, cooling media and temperature monitoring devices may be needed as
      additional measures to determine, minimize and exclude effects of ambient
      temperature on serum marker levels especially when travelling times are long or
      ambient temperatures are high.

PMID- 21740322
TI  - Cystatin C in pre-eclampsia.
AB  - OBJECTIVE: To evaluate diagnostic value of cystatin C serum levels as alternative
      marker of renal function in pre-eclamsia (PE) and compare it with the traditional
      markers of renal function, creatinine and uric acid. In order to investigate the
      possible influence of inflammation on biochemical markers of renal function,
      serum levels of high sensitive CRP were measured (hsCRP). METHODS: In this
      prospective study markers of kidney function were investigated in two groups of
      pregnant women: one with PE (n = 32) and the other of healthy pregnant women (n =
      60). Serum cystatin C levels were measured as well as levels of traditional renal
      markers creatinin and uric acid and levels of high sensitive C-reactive protein.
      RESULTS: Serum levels of cystatin C, creatinine and uric acid were significantly
      higher in the PE group than in the control group. Serum levels of hsCRP were
      higher in approximately the same number of patients with PE (50%) as in normal
      pregnancies (40%), without significant differences in CRP values between the two
      groups of patients. CONCLUSIONS: Cystatin C serum level may have significant role
      as a marker of pre-eclampsia specially when used in combination with uric acid
      levels.

PMID- 21740323
TI  - First trimester uterine artery Doppler for the prediction of preeclampsia and
      foetal growth restriction.
AB  - Feasibility and reproducibility of uterine artery Doppler (UAD) at 11-14
      gestational weeks was recently confirmed. Normal range values were established
      for resistance and pulsatility indexes. A body of evidence supports that the risk
      of developing preeclampsia or foetal growth restriction is highest when UAD
      impedance (evaluated by sus-mentioned indexes or uterine artery notch
      persistence) remains bilaterally high from first to second trimester, whereas the
      risk is lowest when UAD impedance is low from 11 to 14 gestational weeks. In
      unselected women, the sensitivity of 11-14 weeks-UAD is high but the positive
      predictive value is low, and data do not support its introduction as the sole
      predictive test. In models using maternal history and 11-14 weeks-UAD, the
      negative predictive value is high while abnormal UAD may identify a high
      proportion of women that will develop early-onset preeclampsia. Algorithms
      combining biochemical markers could still improve this prediction rate at higher
      cost and complexity.

PMID- 21740324
TI  - Glutamate in vitro effects on human term placental mitochondria.
AB  - OBJECTIVE: Oxidative stress may affect the functionality of placental
      mitochondria, thus contributing to serious complications. For this reason
      research of protective substances is of great importance. Our aim was to
      evaluate, in mitochondria isolated from human term placentas, the effect of in
      vitro glutamate supplementation on their susceptibility to oxidation, on the
      chemico-physical characteristics of mitochondrial membranes, and on peroxidase
      and nitric oxide synthase (NOS) activities. METHODS: The study was performed on
      mitochondria isolated from 20 healthy human term placentas. Specific exclusion
      criteria were: conception by assisted reproduction, chromosomal or other fetal,
      uterine or placental anomalies, gestational diabetes, preeclampsia, intrauterine
      growth restriction (IUGR), a history of smoking and hypertension, proteinuria,
      renal, cardiovascular, hepatic, and endocrine disease, metabolic disorders, and
      current infection or history of all types of infection. RESULTS: Incubation with
      glutamate determined a reduced susceptibility to oxidative stress, an increase in
      mitochondrial membrane fluidity, and a decrease of both peroxidase and NOS
      activities. CONCLUSIONS: On the basis of the observed results, we can hypothesize
      a role for glutamate in the control of lipid peroxidation extent in physiological
      pregnancies, as well as in the prevention of free radical-linked complications
      that can affect the health of both mother and fetus.

PMID- 21740325
TI  - Ethics in neonatology: a look over Europe.
AB  - Advances in perinatal medicine have dramatically improved neonatal survival. End
      of-life decision making for newborns with adverse prognosis is an ethical
      challenge, the ethical issues are controversial and little evidence exists on
      attitudes and values in Europe. OBJECTIVE: to assess the attitudes of the
      neonatal departments in perinatal clinical practice in the hospitals of European
      countries. METHODS: a questionnaire was send to 55 NICUs from 19 European
      countries. RESULTS: Forty five (81.8%) NICUs were Level III. Religion was
      Christian in 90.7% and we observed that in north countries the religion is more
      influent on clinical decisions (p = 0.032). Gestational age was considered with
      no significant difference for clinical investment. North countries consider birth
      weight (p = 0.011) and birth weight plus gestational age (p = 0.024) important
      for clinical investment. In north countries ethical questions should not prevail
      when the decision is made (p = 0.049) and from an ethical point of view, there is
      no difference between withdraw a treatment and do not initiate the treatment (p =
      0.029). More hospitals in south countries administer any analgesia (p = 0.007).
      When the resuscitation is not successful 96.2% provide comfort care. CONCLUSION:
      Our study reveals that cultural and religious differences influenced ethical
      attitudes in NICUs of the European countries.

PMID- 21740326
TI  - Evaluation of postnatal growth of preterm infants.
AB  - The past two decades have seen a progressive improvement in the survival rates of
      preterm infants, especially in neonates <30 weeks of gestational age. These
      neonates constitute the large majority of the population in neonatal intensive
      care units. The correct evaluation of postnatal growth of these babies is
      nowadays of primary concern, although the definition of their optimal postnatal
      growth pattern is still controversial. Concerns have also been raised about the
      strategies to monitor their growth, specifically in relation to the charts used.
      At present the available charts in clinical practice are fetal growth charts,
      neonatal anthropometric charts and postnatal growth charts for term infants. None
      of these, for different reasons, is suitable to correctly evaluate preterm infant
      growth. An international multicentric project has recently started a study aiming
      at building a prescriptive standard for the evaluation of postnatal growth of
      preterm infants and it will be available in the next years providing a population
      that is conceptually as close as possible to the prescriptive approach used for
      the construction of the WHO infant and child growth standards. At present, while
      an international longitudinal standard for evaluating preterm infant postnatal
      growth is lacking, in Italy the best compromise in clinical practice is likely to
      be as follows: new Italian INeS (Italian Neonatal Study) charts up to term;
      International longitudinal charts WHO 2006 or CDC 2002 from term to two years;
      finally the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006
      growth charts could be suitable for monitoring the growth of these infants from
      two years up to 20 years of age.

PMID- 21740327
TI  - Expansion on extracellular matrix deposited by human bone marrow stromal cells
      facilitates stem cell proliferation and tissue-specific lineage potential.
AB  - Our objective was to assess the rejuvenation effect of extracellular matrix (ECM)
      deposited by human bone marrow stromal cells (hBMSCs) on hBMSC expansion and
      tissue-specific lineage differentiation potential. Passage 5 hBMSCs were expanded
      on ECM or conventional plastic flasks (Plastic) for one passage. Cell number was
      counted and immunophenotype profiles were assessed using flow cytometry. Selected
      integrins and proliferation-related pathway signals were assessed using Western
      blot. The expanded cells were evaluated for their chondrogenic potential in a
      pellet culture system with TGF-beta3-containing chondrogenic medium using gross
      morphology, histology, immunostaining, biochemical analysis, real-time polymerase
      chain reaction, Western blot, and biomechanical testing. ECM-expanded hBMSCs were
      further evaluated for their osteogenic potential using Alizarin Red S staining
      and alkaline phosphatase activity assay and for their adipogenic potential using
      Oil Red O staining. ECM-expanded hBMSCs exhibited an enhanced proliferation
      capacity and an acquired robust chondrogenic potential compared to those grown on
      Plastic. ECM expansion decreased intracellular reactive oxygen species and
      increased stage-specific embryonic antigen-4 expression in hBMSCs. ECM expansion
      also upregulated integrins alpha2 and beta5 and induced a sustained activation of
      Erk1/2 and cyclin D1. Interestingly, upregulation of TGF-beta receptor II during
      cell expansion and chondrogenic induction might be responsible for an enhanced
      chondrogenic potential in ECM-expanded hBMSCs. We also found that ECM-expanded
      hBMSCs had an increased osteogenic potential and decreased adipogenic capacity.
      ECM deposited by hBMSCs may be a promising approach to expand BMSCs from elderly
      patients for the treatment of large-scale bone defects through endochondral bone
      formation.

PMID- 21740328
TI  - Septin roles in tumorigenesis.
AB  - Septins are a family of cytoskeleton related proteins consisting of 14 members
      that associate and interact with actin and tubulin. From yeast to humans, septins
      maintain a conserved role in cytokinesis and they are also involved in a variety
      of other cellular functions including chromosome segregation, DNA repair,
      migration and apoptosis. Tumorigenesis entails major alterations in these
      processes. A substantial body of literature reveals that septins are
      overexpressed, downregulated or generate chimeric proteins with MLL in a plethora
      of solid tumors and in hematological malignancies. Thus, members of this gene
      family are emerging as key players in tumorigenesis. The analysis of septins
      during cancer initiation and progression is challenged by the presence of many
      family members and by their potential to produce numerous isoforms. However, the
      development and application of advanced technologies is allowing for a more
      detailed analysis of septins during tumorigenesis. Specifically, such
      applications have led to the establishment and validation of SEPT9 as a biomarker
      for the early detection of colorectal cancer. This review summarizes the current
      knowledge on the role of septins in tumorigenesis, emphasizing their significance
      and supporting their use as potential biomarkers in various cancer types.

PMID- 21740329
TI  - Septins at the annulus of mammalian sperm.
AB  - The annulus is an electron-dense ring structure connecting the midpiece and the
      principal piece of the mammalian sperm flagellum. Proteins from the septin family
      have been shown to localize to the annulus. A septin complex is assembled early
      in spermiogenesis with the cochaperone DNAJB13 and, in mature sperm, associates
      with Testis Anion Transporter 1; SLC26A8 (Tat1), a transmembrane protein of the
      SLC26 family. Studies in mice have shown that the annulus acts as a barrier to
      protein diffusion and controls correct organization of the midpiece. Consistent
      with these findings, absence of the annulus is associated with flagellum
      differentiation defects and asthenozoospermia in humans.

PMID- 21740330
TI  - Head circumference catch-up growth among preterm very low birth weight infants:
      effect on neurodevelopmental outcome.
AB  - AIMS: The purpose of this study was to determine whether head circumference (HC)
      catch-up is associated with improved neurocognitive development. DESIGN: A
      retrospective cohort study was conducted in 179 preterm very low birth weight
      (VLBW) (BW<=1500 g) infants. The infants were born in 2000-2002 and were followed
      to the age of 5.5 years. The association between HC catch-up and
      neurodevelopmental outcome was assessed and perinatal risk factors, infant
      characteristics and nutritional practices associated with HC catch-up were
      determined. RESULTS: HC catch-up occurred in 59 (34%) infants and was positively
      correlated with neurodevelopmental outcome. The likelihood of HC catch-up
      increased with increasing birth weight and gestational age. HC catch-up occurred
      more often with breast milk feeding during hospitalization and with supplemental
      formula feeding at discharge, but decreased in prevalence with longer duration of
      breastfeeding after discharge. HC catch-up was more likely to occur in first-born
      infants and in families with high socioeconomic status. Most HC catch-up occurred
      between birth and three months corrected age. CONCLUSION: Among preterm-VLBW
      infants, there is a close relation between HC growth and neurodevelopmental
      outcome. Efforts to improve neurocognitive outcomes should focus on factors
      associated with HC catch-up.

PMID- 21740331
TI  - TGF-beta signaling in fibrosis.
AB  - Transforming growth factor beta (TGF-beta) is a central mediator of fibrogenesis.
      TGF-beta is upregulated and activated in fibrotic diseases and modulates
      fibroblast phenotype and function, inducing myofibroblast transdifferentiation
      while promoting matrix preservation. Studies in a wide range of experimental
      models have demonstrated the involvement of the canonical activin receptor-like
      kinase 5/Smad3 pathway in fibrosis. Smad-independent pathways may regulate Smad
      activation and, under certain conditions, may directly transduce fibrogenic
      signals. The profibrotic actions of TGF-beta are mediated, at least in part,
      through induction of its downstream effector, connective tissue growth factor. In
      light of its essential role in the pathogenesis of fibrosis, TGF-beta has emerged
      as an attractive therapeutic target. However, the pleiotropic and multifunctional
      effects of TGF-beta and its role in tissue homeostasis, immunity and cell
      proliferation raise concerns regarding potential side effects that may be caused
      by TGF-beta blockade. This minireview summarizes the role of TGF-beta signaling
      pathways in the fibrotic response.

PMID- 21740333
TI  - The role of the laboratory in choosing antibiotics.
AB  - OBJECTIVE: Antimicrobial resistance is one of the biggest problem in medicine at
      the beginning of the third millennium. Antibiotic resistance is frequently
      associated with significant morbidity, longer hospitalization, excess costs and
      mortality. METHODS: In this work we discussed the role of clinical microbiology
      laboratory as an essential part for an effective infection control program,
      especially in management and treatment of "difficult infections". RESULTS: At
      present time, laboratory personnel have a broad range of new technologies that
      they can use to support and enhance the efforts of the infection control staff.
      In addition a network of established experts in the determination of
      antimicrobial breakpoints and in antimicrobial susceptibility testing has been
      constituted in Europe under the auspices of the European Society of Clinical
      Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease
      Prevention and Control (ECDC). CONCLUSION: Qualified personnel and new strategies
      to overcome drug resistance can contribute to solve the microbial infections
      problems.

PMID- 21740332
TI  - Fibrin encapsulation and vascular endothelial growth factor delivery promotes
      ovarian graft survival in mice.
AB  - Ovarian cryopreservation before chemotherapy and autotransplantation post
      treatment can restore fertility to women with premature ovarian failure. Although
      the majority of primordial follicles survive the cryopreservation cycle, the
      follicular pool is reduced after transplantation due to ischemic death.
      Therefore, we engineered a biomaterial-based system to promote angiogenesis in a
      mouse model of ovarian transplantation. To mimic the clinical situation of
      sterility, a bilateral ovariectomy was performed 2 weeks before transplantation,
      during which time serum levels of follicular stimulating hormone rose to
      menopausal levels. Before transplantation, vitrified/thawed ovarian tissue from
      12-day-old C57Bl/6J pups was encapsulated in fibrin modified with heparin-binding
      peptide (HBP), heparin, and loaded with 0.5 MUg vascular endothelial growth
      factor (VEGF). The group transplanted with fibrin-HBP-VEGF had twice as many
      surviving primordial follicles and an increased number of blood vessels relative
      to the no biomaterial control. Transplanted tissue was viable and supported
      natural conception that led to live and healthy offspring. The timeline of live
      births with VEGF delivery suggested that primary follicles survived
      transplantation, and provided the gametes for the first litter. Thus, VEGF
      delivery from fibrin supported integration of the transplant with the host,
      promoted angiogenesis, and enhanced engraftment and function of the tissue.

PMID- 21740334
TI  - Quality assurance of laboratory work and clinical use of laboratory tests in
      general practice in norway: a survey.
AB  - OBJECTIVE: Virtually all the general practices in Norway participate in the
      Norwegian Quality Improvement of Laboratory Services in Primary Care, NOKLUS. In
      order to assess and develop NOKLUS's services, it was decided to carry out an
      investigation in the largest participating group, general practices. DESIGN: In
      autumn 2008 a questionnaire was sent to all Norwegian general practices asking
      for feedback on different aspects of NOKLUS's main services: contact with medical
      laboratory technologists, sending of control materials, use and maintenance of
      practice-specific laboratory binders, courses, and testing of laboratory
      equipment. In addition, attitudes were elicited towards possible new services
      directed at assessing other technical equipment and clinical use of tests.
      RESULTS: Responses were received from 1290 of 1552 practices (83%). The great
      majority thought that the frequency of sending out control material should
      continue as at present, and they were pleased with the feedback reports and
      follow-up by the laboratory technologists in the counties. Even after many years
      of practical experience, there is still a need to update laboratory knowledge
      through visits to practices, courses, and written information. Practices also
      wanted quality assurance of blood pressure meters and spirometers, and many
      doctors wanted feedback on their use of laboratory tests. CONCLUSION: Services
      regarding quality assurance of point-of-care tests, guidance, and courses should
      be continued. Quality assurance of other technical equipment and of the doctor's
      clinical use of laboratory tests should be established as part of comprehensive
      quality assurance.

PMID- 21740335
TI  - Will periodic intravenous injections of conditioned bone marrow cells effectively
      reduce atherosclerosis?
AB  - Maintenance of healthy arteries requires a balance between injuries to the
      arterial wall and processes of intrinsic arterial repair. Such repair requires
      the availability of progenitor cells that are local to the wall itself.
      Progenitor cells from distant reservoirs like the bone marrow may also contribute
      to repair. Arterial repair seems to degrade over a lifetime, particularly with
      risk factors such as smoking and diabetes. Hence, a potential
      preventive/therapeutic strategy for atherosclerosis could be transfusion of
      competent bone marrow cells (BMCs) to restore effective repair in the face of
      arterial injury and depleted endogenous repair reservoirs. The challenge with
      this strategy has been the reliable collection and/or generation of BMCs that
      support arterial repair. In this study, we describe a set of experiments to
      elucidate a method of culturing BMCs that robustly retards atherosclerosis
      development in apolipoprotein E knockout mice. Identifying such a method would
      represent an important step in developing cell-based treatments for patients with
      proclivity for developing atherosclerosis.

PMID- 21740336
TI  - Urine neutrophil gelatinase-associated lipocalin (uNGAL) and netrin-1: are they
      effectively improving the clinical management of sepsis-induced acute kidney
      injury (AKI)?
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) and Netrin-1 have been proposed
      over the past years as emergent biomarkers for the early and accurate diagnosis
      and monitoring of acute kidney injury (AKI). During the early phases of AKI, a
      rapid and massive up-regulation of NGAL mRNA takes place in the thick ascending
      limb of Henle's loop and in the collecting ducts, and therefore, changes in
      urinary NGAL (uNGAL) excretion seem to be more specific than plasma NGAL in
      assessing early kidney injury. The availability of a new automated immunoassay
      for measuring uNGAL facilitates its introduction in the clinical routine,
      especially in an emergency setting. However, in critically ill newborns AKI often
      develops during sepsis, which in turn induces an up-regulation of NGAL mRNA in
      neutrophils. To improve the effectiveness of therapeutic treatment in septic
      newborns with AKI, there is the need to accurately distinguish NGAL molecular
      forms originating within the distal nephron from those originating from
      neutrophils. This concise review summarizes properties and perspectives of uNGAL
      and Netrin-1 for their appropriate clinical utilization.

PMID- 21740337
TI  - Impact of providing vitamin A to the routine pulmonary care of extremely low
      birth weight infants.
AB  - OBJECTIVE: The objective of this study was to determine if the continued use of
      vitamin A in a nursery utilizing early surfactant and nasal continuous positive
      airway pressure (CPAP) was warranted. STUDY DESIGN: A retrospective, cohort study
      of appropriately sized, preterm neonates weighing <=1000 g at birth was
      conducted. Two time periods were compared: Pre-Vitamin A was composed of
      extremely low birth weight who were routinely cared for with early nasal CPAP (n
      = 76); and Post-Vitamin A (n = 102) consisted of ELBWs who were cared for similar
      to Pre-Vitamin A, but with the addition of vitamin A. Outcome variables included
      the incidence of BPD and other pulmonary and major neonatal morbidities. RESULTS:
      Between Pre-Vitamin A and Post-Vitamin A the incidence of moderate to severe BPD
      decreased by 11%, from 33% to 22% (p = 0.2). No difference was found in the
      number of ventilator days or in the incidence of any other neonatal morbidity or
      mortality, including intraventricular hemorrhage, necrotizing enterocolitis, or
      patent ductus arteriosus requiring surgical ligation. CONCLUSION: In a neonatal
      unit utilizing early surfactant followed by nasal CPAP at delivery, supplementing
      extremely premature neonates with vitamin A demonstrated a trend towards a
      decrease in the incidence of moderate to severe BPD; however, this change
      requires a larger sample to verify in the future.

PMID- 21740338
TI  - A novel approach for studying microcirculation in bone defects by intravital
      fluorescence microscopy.
AB  - Angiogenic and inflammatory responses to biodegradable scaffolds were previously
      studied using the dorsal skinfold chamber for testing different scaffold
      materials. In this model, the angiogenic response originates from the soft tissue
      of the skin. Herein, we introduce a new model that allows the study of developing
      microcirculation of bone defects for testing tissue-engineered constructs. A bone
      defect was prepared in the femur of Balb/c mice by inserting a pin for
      intramedullary fixation, and a custom-made observation window fixed over the
      defect allowed constant observation. This study included three different groups:
      empty defect (control), defect filled with porous poly(L-lactide-co-glycolide),
      and beta-tricalcium-phosphate scaffolds. Starting from 6 days after surgery,
      angiogenesis, neovascularization, leukocyte-endothelial cell interaction, and
      microvascular permeability were analyzed over 22 days by using intravital
      fluorescence microscopy. The empty defects showed no signs of angiogenesis during
      the observation period, but a distinct increase of capillary density was detected
      in the scaffold-containing defects. Surprisingly, the histological sections of
      the scaffold-treated defects showed new bone formation 22 days after
      implantation. We present a new bone chamber model for intravital long-term study
      of scaffold materials suitable for bone reconstruction in mice by using
      fluorescence microscopy.

PMID- 21740339
TI  - Acidic preparations of lysed platelets upregulate proliferative pathways in
      osteoblast-like cells as demonstrated by genome-wide microarray analysis.
AB  - Platelets contain numerous growth factors essential for wound and fracture
      healing. We investigated the gene expression in human osteoblast-like cells
      stimulated with lysed platelets prepared in acidic, neutral, or alkaline buffers.
      Lysed platelets prepared in buffers at pH 5.4, 7.4, and 7.9, were added after
      neutralization to hFOB 1.19 cells. Genome-wide microarray analysis was performed
      using the Affymetrix GeneChip 7G Scanner. Biometric, cluster, and pathway
      analyses were performed with GeneSpring GX. Biometric analyses demonstrated that
      53 genes were differentially regulated (p <= 0.005, >=2-fold increase). Pathway
      analysis revealed 10 significant pathways of which eight are common ones
      regulating bone formation and cancer growth. Eleven genes were selected for
      quantitative real-time polymerase chain reaction (PCR) based on the microarray
      analysis of the lysed platelets prepared in the pH 5.4 experiments. In
      conclusion, acidic preparations of lysed platelet concentrates release factors
      essential for cell proliferation and particularly cell metabolism under hypoxic
      conditions. The genetic response from these factors was dominated by genes
      associated with the same pathways observed in bone formation and cancer growth.
      Activation of TGF-beta in the acidic preparation could be a stimulatory key
      factor of cell proliferation. These results support the hypothesis that
      acidification of platelets modifies the stimulatory response of mesenchymal cells
      in vitro, which is analogous with the observed milieu of a low pH present in
      wound and fracture sites, as well as in growing tumors.

PMID- 21740340
TI  - The complete mitochondrial genome of the American lobster, Homarus americanus
      (Crustacea, Decapoda).
AB  - Although relatively a large number of the complete mitochondrial genome sequences
      have been determined from various decapod species (29 mtDNA sequences reported so
      far), the information for the infraorder Astacidea (including lobsters,
      crayfishes, and their relatives) is very limited and represented by only one
      complete sequence from the Australian freshwater crayfish species Cherax
      destructor. In this study, we determined the complete mitochondrial DNA sequence
      of Homarus americanus, the first representative of the family Nephropidae to be
      fully characterized. Comparison of the gene arrangement reveals that H.
      americanus mtDNA is identical to those of other pancrustacean species but differs
      from the other astacidean species (C. destructor). Based on these data, it can be
      assumed that an idiosyncratic gene order discovered in C. destructor mtDNA may be
      secondarily acquired from the ancestral lineage of the Astacidea.

PMID- 21740341
TI  - Complete mitochondrial genome of the Korean stumpy bullhead Pseudobagrus
      brevicorpus (Siluriformes, Bagridae).
AB  - We describe the complete mitochondrial genome sequence of the Korean stumpy
      bullhead Pseudobagrus brevicorpus, which is an endangered species in Korea. The
      circle genome (16,526 bp) consists of 13 protein coding, 22 tRNA, 2 rRNA genes
      and 1 control region. It has the typical vertebrate mitochondrial gene
      arrangement.

PMID- 21740342
TI  - The micros in harmony: microRNA and microenvironment.

PMID- 21740343
TI  - Intraperitoneal N-acetylcysteine for acute iron intoxication in rats.
AB  - Free radical formation and release of oxidant agents have been suggested as
      possible mechanisms for tissue damage in acute iron intoxication. N
      acetylcysteine (NAC), a glutathione substitute and an antioxidant, is widely used
      as an antidote for various intoxications. Our aim was to determine whether
      intraperitoneal (i.p.) NAC would reduce the mortality of rats after acute, toxic
      oral doses of iron. Male Wistar rats were studied in three phases. In the first
      phase, animals were assigned to groups 1 (distilled water by gavage) and 2 (i.p.
      NAC) and observed for survival. In the second phase, rats were assigned to groups
      3 (400 mg/kg elemental iron orally) and 4 (400 mg/kg elemental iron, followed by
      150 mg/kg i.p. NAC). Survival was observed. Because most rats in Group 3 died
      within 90 minutes after iron administration, a third phase was conducted in order
      to allow for comparison of iron and transaminase serum levels after the
      administration of iron and NAC (group 5: n = 10). Mortality was significantly
      lower in rats treated with iron and NAC, compared to those treated with iron (P =
      0.016). Median serum iron level was significantly lower among rats treated with
      iron and NAC, compared with rats treated with iron alone (P = 0.002). In a rat
      model of acute iron intoxication, i.p. administration of NAC may decrease serum
      iron levels and mortality.

PMID- 21740344
TI  - Dementia management programme in a community setting and the use of psychotropic
      drugs in the elderly population.
AB  - BACKGROUND AND OBJECTIVE: The number of elderly persons in society is increasing,
      placing additional demands on the public health system. Extensive use of drugs is
      common in the elderly, and in patients with dementia this further increases their
      vulnerability. Since 1998 the municipality of Kalmar, Sweden, has worked with a
      dementia management programme that focuses on early intervention in order to
      identify the patient's help needs at an early stage. An important part of the
      programme aims at optimizing pharmacological treatment. The objective of the
      present study is to evaluate whether the dementia programme had a secondary
      effect on the use of psychotropic medication in the elderly population in
      general. DESIGN AND SETTING: A retrospective, drug utilization study analysing
      the use of selected drug categories by the elderly (75 years and older) in the
      Kalmar municipality compared with the whole of Sweden. RESULTS AND CONCLUSIONS:
      The results suggest that the dementia programme contributed to an improvement in
      psychotropic drug use in the elderly as a secondary effect. Furthermore, the
      implementation of this programme did not require allocation of extra funding.

PMID- 21740345
TI  - Risk factors for suicide within a year of discharge from psychiatric hospital: a
      systematic meta-analysis.
AB  - BACKGROUND: The increased risk of suicide in the period after discharge from a
      psychiatric hospital is a well-recognized and serious problem. OBJECTIVE: The aim
      of this study was to establish the risk factors for suicide in the year after
      discharge from psychiatric hospitals and their usefulness in categorizing
      patients as high or low risk for suicide in the year following discharge. METHOD:
      A systematic meta-analysis of controlled studies of suicide within a year of
      discharge from psychiatric hospitals. RESULTS: There was a moderately strong
      association between both a history of self-harm (OR = 3.15) and depressive
      symptoms (OR = 2.70) and post-discharge suicide. Factors weakly associated with
      post-discharge suicide were reports of suicidal ideas (OR = 2.47), an unplanned
      discharge (OR = 2.44), recent social difficulty (OR = 2.23), a diagnosis of major
      depression (OR = 1.91) and male sex (OR = 1.58). Patients who had less contact
      with services after discharge were significantly less likely to commit suicide
      (OR = 0.69). High risk patients were more likely to commit suicide than other
      discharged patients, but the strength of this association was not much greater
      than the association with some individual risk factors (OR = 3.94, sensitivity =
      0.40, specificity = 0.87). CONCLUSIONS: No factor, or combination of factors, was
      strongly associated with suicide in the year after discharge. About 3% of
      patients categorized as being at high risk can be expected to commit suicide in
      the year after discharge. However, about 60% of the patients who commit suicide
      are likely to be categorized as low risk. Risk categorization is of no value in
      attempts to decrease the numbers of patients who will commit suicide after
      discharge.

PMID- 21740346
TI  - Asymptomatic bacteriuria in users of low-dose combined oral contraceptives.
AB  - OBJECTIVES: To investigate the association between oral contraceptive use and the
      prevalence of asymptomatic bacteriuria in women. METHODS: The study was conducted
      on healthy women of childbearing age who either used low-dose combined oral
      contraceptives (COCs; cases) or applied the withdrawal method (controls). A
      positive urine culture with a colony count of more than 10(5)/ml, with the same
      bacteria on two consecutive specimens, was defined as asymptomatic bacteriuria.
      Pyuria was defined as the presence of >= 10 leukocytes per mm3 of urine. RESULTS:
      Overall, 369 women in the COC group and 364 in the control group were evaluated.
      The mean ages of women in the COC group and of controls were 29.9 +/- 5.4 years
      and 30.4 +/- 6.0 years, respectively (p = 0.280). Asymptomatic bacteriuria was
      detected in 2.4% of COC users and 1.9% of the controls (p = 0.633). Pyuria was
      found in 16% of the cases and 18.1% of the controls (p = 0.441). None of these
      differences was statistically significant. There was no significant association
      between duration of COC usage (< 1 year vs. >= 1 year) and asymptomatic
      bacteriuria. CONCLUSION: Use of low-dose COCs (even long-term) does not increase
      the risk of asymptomatic bacteriuria.

PMID- 21740347
TI  - CuO and ZnO nanoparticles differently affect the secretion of fluorescent
      siderophores in the beneficial root colonizer, Pseudomonas chlororaphis O6.
AB  - To understand the impact of environmental deposition of CuO and ZnO nanoparticles
      (NPs) on the production of bacterial metabolites, we examined the effects of
      their sub-lethal levels on the production of a pyoverdine (PVD) siderophore in a
      plant-beneficial bacterium, Pseudomonas chlororaphis O6 (PcO6). The NPs were
      characterized for size, shape, surface charge and ion release. Production of PVD
      by the cells was evaluated by fluorimetry and the expression of genes for PVD
      biosynthesis and export. The level of PVD in the presence of ZnO NPs was similar
      to that with Zn ions at 24 h, but the NPs maintained higher level than control at
      48 h. In contrast, the reduction in PVD by CuO NPs was not duplicated by Cu ions.
      Expression of a gene encoding an inner membrane PVD transporter was inhibited by
      CuO NPs, supporting the observed low amounts of external PVD detected in those
      cells. These findings revealed NP-specific effect for CuO NPs on PcO6 metabolism,
      while for ZnO NPs, the release of ions was important. Because siderophores are
      part of the chemical communication between soil microbes and plants, the outcomes
      of plant-microbe interactions could be affected by responses to NPs.

PMID- 21740348
TI  - A high G418-resistant neo(R) transgenic mouse and mouse embryonic fibroblast
      (MEF) feeder layers for cytotoxicity and gene targeting in vivo and in vitro.
AB  - Aminoglycoside antibiotics have been in use since 1944 with the discovery of
      streptomycin. The aim of this study was to derive a new, highly resistant
      multicopy neo(R) transgenic mouse strain, named TgN3Ems, by random insertion of
      the plasmid, pPGKneobpA, and compare the level of drug resistance of wild-type
      and transgenic mice in vivo and corresponding primary mouse embryonic fibroblasts
      (MEFs) in vitro to a model neomycin analog, G418. The expression neoR in
      transgenic animals caused a 5-fold increase in the approximate lethal dose of
      G418, compared to wild type. No adverse pathological changes were found for the
      transgenic mice treated with G418, as they all died within minutes after
      injection. In contrast, the G418 treatment of wild-type mice resulted in a marked
      liver and kidney toxicity detected microscopically and via increases of serum
      biomarkers for liver and kidney damage. In addition, there was a mild bone marrow
      and lymphoid depletion. In in vitro studies, the transgenic MEFs survived 20-fold
      higher G418 levels, compared to the wild-type MEF cells. Therefore, TgN3Ems
      transgenic mice could be used as a source of G418-resistant feeder cells for gene
      targeting. Since the expression of drug-resistance genes in transgenic animals
      confers resistance to toxicity, the TgN3Ems mice might serve as a tool applicable
      in drug design.

PMID- 21740349
TI  - The contribution of thymic stromal abnormalities to autoimmune disease.
AB  - In essence, normal thymus function involves the production of a broad repertoire
      of alphabetaT cells capable of responding to foreign antigens with low risk of
      autoreactivity. Thymic epithelial cells are an essential component of the thymic
      stromal microenvironment, promoting the growth and export of self-tolerant
      thymocytes. Autoimmune disease, resulting from a loss of self-tolerance, is
      clinically and genetically complex, and accordingly has many potential
      etiological origins. However, it is commonly linked to defects in the thymic
      epithelial microenvironment. The study of autoimmune-linked thymic stromal
      dysfunction has indisputably advanced our understanding of T cell tolerance;
      notably, a field-wide paradigm shift occurred when autoimmune regulator (Aire)
      was found to drive expression of a multitude of peripheral tissue-restricted
      antigens in medullary thymic epithelial cells. Many other associations with
      polygenically controlled autoimmune diseases have been reported but are more
      difficult to definitively dissect. Paradoxically, immunodeficiency and age
      related immunosenescence are also linked with increased autoimmunity. Here we
      discuss the theoretical basis and the evidence gathered thus far to support these
      associations.

PMID- 21740351
TI  - T cell proliferation and homeostasis: an emerging role for the cell cycle
      inhibitor geminin.
AB  - Thymic T cell differentiation to peripheral T cells aims to assist the generation
      of effector cells mediating adaptive immune responses. During this process, which
      takes place during embryogenesis and in adulthood, proliferation is coupled with
      changes in chromatin organization and transcription. Moreover, B and T
      lymphocytes start to proliferate and rapidly expand their numbers when activated
      following an encounter with an antigen. This expansion phase is accompanied by
      differentiation of naive T cells and is followed by a period of population
      contraction, resulting in only a small fraction of the expanded population
      surviving and entering the memory cell pool. The kinetics of the expansion and
      contraction affect the speed of antigen clearance and the clinical course of
      disease. Molecules that are involved in the coordination of proliferation,
      chromatin reorganization, and transcriptional regulation are likely to play an
      important role in T cell generation, homeostasis, and disease. Here we review how
      cell cycle regulators affect lymphoid system development and homeostasis and
      discuss recent evidence implicating the cell cycle inhibitor Geminin in this
      process. Geminin has been shown to coordinate proliferation and differentiation
      by regulating cell cycle progression, chromatin organization, and transcription
      in the nervous system. In the immune system, progenitor T cell commitment and
      differentiation progresses normally in the absence of Geminin. However, Geminin
      is required for TCR response in vitro and T cell proliferation upon lymphopenia
      induced proliferation, suggesting that Geminin might be an essential factor for T
      cell expansion during the immune response.

PMID- 21740350
TI  - Regulatory T cells for tolerance therapy: revisiting the concept.
AB  - The discovery of regulatory T cells (Tregs) as a crucial component of peripheral
      down-regulation of immunity to self and allogeneic antigens has raised legitimate
      hope for the development of Treg-based clinical protocols for tolerance to
      allografts. The present review addresses the question of whether therapeutic
      Tregs are ready to enter the clinical transplantation arena. In light of recent
      experimental observations, we will revisit some fundamentals of T cell and Treg
      biology that stress the need for further studies prior to applications and
      provide conceptual cues for novel therapeutic approaches.

PMID- 21740352
TI  - Function of histone deacetylase inhibitors in inflammation.
AB  - Histone deacetylases (HDACs) display multi-faceted roles in coordinating the
      interaction of intracellular signaling pathways with chromatin remodeling and
      transcription factor function to finely specify gene alterations and maintenance
      of gene expression during cellular activation, proliferation, and
      differentiation. These processes, epigenetic and non-epigenetic, are critical to
      the development of both the adaptive and innate arms of the mammalian immune
      system, and the measured initiation and resolution of immune responses.
      Pharmacological modulators of HDAC activity have demonstrated uniformly potent
      anti-inflammatory effects in experimental animal models of these diseases, in
      relevant immune and stromal cell populations from patients, as well as initial
      successes in the clinic. Recent studies have identified key roles for specific
      HDACs in regulating immune function, as well as alterations in HDAC expression
      and function in a number of immune-mediated inflammatory diseases (IMIDs), which
      may contribute to pathology in these diseases. Here, we review recent advances in
      our understanding of HDAC function in the immune system, their contribution to
      IMIDs, and the therapeutic potential of altering HDAC activity in IMIDs.

PMID- 21740353
TI  - Fusogenic oncolytic herpes simplex viruses as a potent and personalized cancer
      vaccine.
AB  - The recent FDA approval of Sipuleucel-T for the treatment of prostate cancer
      represents an important milestone of cancer immunotherapy, which, for the first
      time, validates the concept of bringing true clinical benefit to cancer patients
      by stimulating patients' own anti-tumor immunity. Among the different
      experimental cancer immunotherapies, oncolytic virotherapy may represent a low
      cost yet potent and personalized cancer vaccine for the treatment of solid
      tumors. This review describes the constructions of several human herpes simplex
      virus (HSV)-derived oncolytic viruses as candidate cancer vaccines, which induce
      specific and potent anti-tumor immunity in pre-clinical models, and thus
      resulting in stronger overall anti-tumor efficacy as compared to oncolytic effect
      alone. This article also describes the approaches to enhance the antitumor
      immunity of oncolytic HSVs, and in particular, the key role played by integrating
      membrane-fusion activity into these viruses. Additionally, this article reviews
      the potential effect of certain chemotherapeutic agents (e.g. cyclophosphamide)
      in boosting antitumor immunity induced by oncolytic HSV, and the mechanisms
      behind it. In summary, all the preclinical and clinical data have suggested that
      HSV-based oncolytic virotherapies could likely be developed as a new generation
      of cancer vaccines for the treatment of solid tumors.

PMID- 21740355
TI  - Oncolytic viruses for induction of anti-tumor immunity.
AB  - Oncolytic virotherapy is an evolving but, as yet, unrealized treatment option for
      cancer. This approach harnesses the cancer-restricted replicative activity of
      engineered viruses to achieve tumor cell kill. Tumors that are resistant to
      chemotherapy or radiotherapy can be susceptible to viral oncolysis because of
      distinct cell kill mechanisms. There is now compelling evidence that collateral
      induction of anti-tumor immune responses contributes substantially to viral
      antitumor activities. In addition to the expected anti-viral immune clearance,
      the "danger" signal created by virus-infected cells can generate immune co
      stimulation known to override immune suppression and reverse tolerance within the
      tumor microenvironment. Our recent findings indicate that immune activation
      augments the clinical outcomes of oncolytic virotherapy. Strikingly similar and
      robust clinical response rates ( > 25%) were observed among advanced cancer
      patients following intratumoral treatments with adenoviral (AdDelta24) and herpes
      simplex (JS1/34.5-/47) constructs armed with an integrated granulocyte-macrophage
      colony-stimulating factor (GMCSF) payload. Both agents produced regressions in
      injected as well as distant, uninjected lesions, demonstrating systemic
      effectiveness. We discuss the innate and adaptive immune activating events that
      may contribute to these clinical outcomes, and examine systemic delivery
      strategies to tilt the immunological balance from viral clearance to tumor
      elimination.

PMID- 21740356
TI  - The molecular basis of herpesviruses as oncolytic agents.
AB  - Herpes simplex viruses (HSVs) have entered clinical trials as oncolytic agents.
      The following properties make them good candidates. It is a mild pathogen; drugs
      (Aciclovir) are available to control viral infection; the large genome is
      amenable to genetic engineering, they can be rendered cancer-specific by deletion
      of genes, envelope glycoproteins allow the insertion of heterologous ligands to
      achieve modification of the natural tropism. Genetically modified HSVs have been
      thoroughly tested in humans. New generation recombinants retargeted to cancer
      specific heterologous receptors have been generated and are presently evaluated
      in pre-clinical settings. They will be reviewed along with the molecular bases of
      cancer specificity and the strategies for the enhancement of oncolytic potential
      of HSV recombinants.

PMID- 21740357
TI  - Clinical development of oncolytic viruses in China.
AB  - The oncolytic virus, being a promising new therapeutic strategy for cancer, has
      inspired a wave of recent clinical research and development in China. The first
      commercialized oncolytic virus, Oncorine, was approved by Chinese SFDA in
      November 2005 for nasopharyngeal carcinoma combined with chemotherapy. Since
      then, a number of oncolytic viruses have been moved into clinical trials. Among
      these are the armed oncolytic adenoviruses such as H103 (expressing the heat
      shock protein) currently has finished phase I trial, and KH901 (expressing GM
      CSF) now launched in phase II trial In this review, we will discuss the current
      status of ongoing oncolytic virus projects being conducted at various clinical
      stages in China, including the preliminary market response for Oncorine after it
      was launched into the Chinese market in 2006.

PMID- 21740354
TI  - Bugs and drugs: oncolytic virotherapy in combination with chemotherapy.
AB  - Single agent therapies are rarely successful in treating cancer, particularly at
      metastatic or end stages, and survival rates with monotherapies alone are
      generally poor. The combination of multiple therapies to treat cancer has already
      driven significant improvements in the standard of care treatments for many types
      of cancers. The first combination treatments exploited for cancer therapy
      involved the use of several cytotoxic chemotherapy agents. Later, with the
      development of more targeted agents, the use of novel, less toxic drugs, in
      combination with the more classic cytotoxic drugs has proven advantageous for
      certain cancer types. Recently, the combination of oncolytic virotherapy with
      chemotherapy has shown that the use of these two therapies with very distinct
      anti-tumor mechanisms may also lead to synergistic interactions that ultimately
      result in increased therapeutic effects not achievable by either therapy alone.
      The mechanisms of synergy between oncolytic viruses (OVs) and chemotherapeutic
      agents are just starting to be elucidated. It is evident, however, that the
      success of these OV-drug combinations depends greatly on the particular OV, the
      drug(s) selected, and the cancer type targeted. This review summarizes the
      different OV-drug combinations investigated to date, including the use of second
      generation armed OVs, which have been studied with the specific purpose of
      generating synergistic interactions with particular chemotherapy agents. The
      known mechanisms of synergy between these OV-drug combinations are also
      summarized. The importance of further investigating these mechanisms of synergy
      will be critical in order to maximize the therapeutic efficacy of OV-drug
      combination therapies in the future.

PMID- 21740358
TI  - Strategy of Cancer Targeting Gene-Viro-Therapy (CTGVT) a trend in both cancer
      gene therapy and cancer virotherapy.
AB  - Cancer Targeting Gene-Viro-Therapy (CTGVT) and Gene Armed Oncolytic Virus Therapy
      (GAOVT) both are identical by inserting an antitumor gene into an oncolytic
      virus. This approach has gradually become a hot topic in cancer therapy, because
      that CTGVT (GAOVT) has much higher antitumor than that of either gene therapy
      alone or oncolytic virotherapy alone. We proposed the CTGVT strategy in 1999
      2001, insisted it as a long term systematic approach to be examined over 10 years
      and have published 68 SCI papers some in good Journals. The CD gene armed
      oncolytic adenovirus therapy (GAOVT) for cancer treatment with potent antitumor
      effect was also named in our laboratory in 2003. Several modifications to CTGVT
      will be carried out by our group and will be introduced briefly in this paper.
      Most importantly, the modifications of CTGVT usually resulted in complete
      eradication of xenograft tumors in nude mice. In future best antitumor drugs may
      emerge from the modified CTGVT strategy and not from either gene therapy or
      virotherapy alone.

PMID- 21740359
TI  - Oncolytic HSV-1 virotherapy: clinical experience and opportunities for progress.
AB  - Oncolytic virotherapy with mutants derived from Herpes simplex virus (HSV) type 1
      exhibit significant antitumor effects in preclinical models. Several mutants have
      now been tested in clinical trials for a variety of cancer types, and all have
      been found to be safe. While there have been hints of antitumor efficacy with
      prolonged survival in some cases compared with historical controls, dramatic
      responses have been elusive. We review the clinical experience published to date
      and discuss some of the biologic factors that may be limiting for virus infection
      and spread, as well as new strategies currently under development to enhance
      antitumor efficacy.

PMID- 21740360
TI  - Targeted oncolytic herpes simplex viruses for aggressive cancers.
AB  - Herpes simplex virus (HSV) is a well-known vector that is often used for gene
      therapy to treat cancers. The most attractive feature of HSV is its ability to
      destroy tumors through a distinctive oncolytic mechanism where the virus can
      destroy cancer cells via cell lysis, a killing function that no anti-cancer drugs
      can mimic. Importantly, HSV is a safe and effective virus that can be easily
      manipulated to preferentially replicate in tumor cells. In the last 20 years of
      reengineering efforts, a number of HSV designs, including the classical G207,
      have been focused on deleting viral genes in order to render the virus tumor
      specific. Although such designs can successfully destroy tumor xenografts in
      animal models, with minimal impact on normal tissues, a common trade-off is the
      marked attenuation of the virus. This problem is most profound in many clinical
      tumors, where virus dissemination is often hindered by the difficult cellular and
      molecular terrain of the human tumor mass. In order to harness all of HSV's
      replication potential to destroy tumor cells, efforts in our lab, as well as
      others, last several years have been focused on engineering an oncolytic HSV to
      target tumor cells without deleting any viral genes, and have since generated
      highly tumor specific viruses including our transcriptional translational dually
      regulated HSV (TTDR-HSV). In this review, we will discuss the improvements
      associated with the newer TTDR-HSV design compared to the classical defective HSV
      designs such as G207 and tk- HSV. Lastly, we will review additional cellular
      features of aggressive tumors, such as their immense cellular heterogeneity and
      volatility, which may serve to hinder the dissemintation of TTDR-HSV. The
      challenge for future studies would be to explore how TTDRHSV could be redesigned
      and/or employed with combinatorial approaches to better target and destroy the
      heterogeneous and dynamic cell populations in the aggressive tumor mass.

PMID- 21740362
TI  - Synergistic interaction of telomerase-specific oncolytic virotherapy and
      chemotherapeutic agents for human cancer.
AB  - Replication-selective tumor-specific viruses present a novel approach for
      treatment of neoplastic disease. These vectors are designed to induce virus
      mediated lysis of tumor cells after selective viral propagation within the tumor.
      Telomerase activation is considered to be a critical step in carcinogenesis
      through the maintenance of telomeres, and its activity correlates closely with
      human telomerase reverse transcriptase (hTERT) expression. We constructed an
      attenuated adenovirus 5 vector, in which the hTERT promoter element drives
      expression of E1 genes, OBP-301 (Telomelysin). Since only tumor cells that
      express telomerase activity would activate this promoter, the hTERT proximal
      promoter allows for preferential expression of viral genes in tumor cells,
      leading to selective viral replication and oncolytic cell death. OBP-301 alone
      exhibited substantial antitumor effects both in animal models and in clinical
      trials; data regarding combination therapy with OBP-301 and chemotherapeutic
      agents are preliminary but encouraging. This article reviews synergistic
      interaction of virotherapy and chemotherapy, and illustrates the potential
      application for the treatment of human cancer.

PMID- 21740361
TI  - Attenuated oncolytic measles virus strains as cancer therapeutics.
AB  - Attenuated measles virus vaccine strains have emerged as a promising oncolytic
      vector platform, having shown significant anti-tumor activity against a broad
      range of malignant neoplasms. Measles virus strains derived from the attenuated
      Edmonston-B (MV-Edm) vaccine lineage have been shown to selectively infect,
      replicate in and lyse cancer cells while causing minimal cytopathic effect on
      normal tissues. This review summarizes the preclinical data that led to the rapid
      clinical translation of oncolytic measles vaccine strains and provides an
      overview of early clinical data using this oncolytic platform. Furthermore, novel
      approaches currently under development to further enhance the oncolytic efficacy
      of MV-Edm strains, including strategies to circumvent immunity or modulate immune
      system responses, combinatorial approaches with standard treatment modalities,
      virus retargeting as well as strategies for in vivo monitoring of viral
      replication are discussed.

PMID- 21740363
TI  - Pro-oncogenic cell signaling machinery as a target for oncolytic viruses.
AB  - Viruses function in close harmony with the signaling machinery of their host.
      Upon exposure to the cell, a battery of viral products become engaged in boosting
      friendly signaling elements of the host or suppressing harmful ones. The
      efficiency of viral replication is indeed the biological outcome of this
      interaction between cellular and host signaling molecules. Oncolytic viruses,
      natural or man-made, follow the same set of rules of engagement. Pro-oncogenic
      cell signaling machinery, therefore, is undoubtedly the most important area
      influencing the development of the next generation of effective, specific and
      rationally designed oncolytic viruses. Ras signaling, with its central role in
      what is known today as molecular oncology, is an attractive topic for studying
      the behavior of viruses versus cancer cells and to develop strategies to target
      cancer cells on the basis of such platform. This work reviews the development of
      oncolytic herpes viruses capable of targeting Ras signaling pathway along with a
      few other examples of viruses which are developed to contain specificity for
      certain pro-oncogenic characteristics of their host cells.

PMID- 21740364
TI  - Recent clinical experience with oncolytic viruses.
AB  - There has been interest in using viruses to treat cancer for over a century.
      Recent clinical efforts, driven on by significant preclinical advances, have
      focussed on the safety of using replication-competent viruses. Recently published
      clinical trials of six oncolytic viruses (adenovirus, reovirus, measles, herpes
      simplex, Newcastle disease virus and vaccinia) have added to the accumulating
      data that endorse oncolytic viruses as a safe and well tolerated treatment
      approach. Conclusive evidence of efficacy remains to be demonstrated, but
      randomised clinical trials are now underway.

PMID- 21740365
TI  - Targeted and armed oncolytic poxviruses for cancer: the lead example of JX-594.
AB  - Oncolytic viruses (OVs) are designed to replicate in, and subsequently lyse
      cancer cells. Numerous oncolytic virus platforms are currently in development.
      Here we review preclinical and clinical experience with JX-594, the lead
      candidate from the targeted and armed oncolytic poxvirus class. JX-594 is derived
      from a vaccinia vaccine strain that has been engineered for 1) enhanced cancer
      targeting and 2) has been "armed" with the therapeutic transgene
      granulocytemacrophage colony stimulating factor (GM-CSF) to stimulate anti
      tumoral immunity. Poxviruses have many ideal features for use as oncolytic
      agents. The development of oncolytic vaccinia viruses is supported by a large
      safety database accumulated in the smallpox eradication program. In addition,
      poxviruses have evolved unique capabilities for systemic spread through the blood
      that can be harnessed for the treatment of metastatic disease. JX-594
      demonstrates a high degree of cancer selectivity and systemic efficacy by
      multiple mechanisms-of-action (MOAs) in preclinical testing. Data from Phase 1
      and 2 clinical trials has confirmed that these features result in potent and
      systemic efficacy in patients with treatment refractory metastatic cancers.

PMID- 21740366
TI  - Mining the adenovirus "virome" for systemic oncolytics.
AB  - Adenoviruses (Ads) are arguably one of the most potent viruses for in vivo gene
      therapy, vaccine, and oncolytic applications. The attraction for the use of Ads
      stems from their ability to infect a wide range of dividing and non-dividing cell
      types in some cases to efficiencies of nearly 100%. Additional benefits include
      their stability, the ability to purify the vector to concentrations of up to 1013
      particles/ml, and the fact that viral vectors self-assemble into particles of
      specific size (~100 nm). The vast majority of clinical applications of Ad have
      utilized Ad serotype 5 (Ad5) viruses. Considering that at least half of humans
      are already immune to Ad5, Ad5 oncolytics may not be optimal for clinical
      translation. Given this and that there are 54 different serotypes of human Ads,
      this review considers the utility of "mining" these alternate Ad serotypes for
      viruses that can evade Ad5 immunity and kill different types of cancer.

PMID- 21740367
TI  - ?

PMID- 21740368
TI  - L-PRP/L-PRF in esthetic plastic surgery, regenerative medicine of the skin and
      chronic wounds.
AB  - The use of platelet concentrates for topical use is of particular interest for
      the promotion of skin wound healing. Fibrin-based surgical adjuvants are indeed
      widely used in plastic surgery since many years in order to improve scar healing
      and wound closure. However, the addition of platelets and their associated growth
      factors opened a new range of possibilities, particularly for the treatment of
      chronic skin ulcers and other applications of regenerative medicine on the
      covering tissues. In the 4 families of platelet concentrates available, 2
      families were particularly used and tested in this clinical field: L-PRP
      (Leukocyte- and Platelet-rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich
      Fibrin). These 2 families have in common the presence of significant
      concentrations of leukocytes, and these cells are important in the local cleaning
      and immune regulation of the wound healing process. The main difference between
      them is the fibrin architecture, and this parameter considerably influences the
      healing potential and the therapeutical protocol associated to each platelet
      concentrate technology. In this article, we describe the historical evolutions of
      these techniques from the fibrin glues to the current L-PRP and L-PRF, and
      discuss the important functions of the platelet growth factors, the leukocyte
      content and the fibrin architecture in order to optimize the numerous potential
      applications of these products in regenerative medicine of the skin. Many
      outstanding perspectives are appearing in this field and require further
      research.

PMID- 21740369
TI  - The role of "eye platelet rich plasma" (E-PRP) for wound healing in
      ophthalmology.
AB  - Blood derived products have demonstrated their capacity to enhance healing and
      stimulate the regeneration of different tissues and this enhancing effect is
      attributed to the growth factors and bioactive proteins that are synthesized and
      present in blood. Eye platelet rich plasma (E-PRP) provides higher concentration
      of essential growth factors and cell adhesion molecules by concentrating
      platelets in a small volume of plasma as compared with autologous serum, the
      latter being used widely in ophthalmology for epithelial wound healing of the
      cornea for the last two decades. These growth factors and cell adhesion molecules
      have a major role in wound healing and enhance the physiological process at the
      site of the injury/surgery via eye drops or clot. E-PRP has been used more
      recently, and has achieved successful outcomes in peer-review articles in the
      treatment of dormant ulcers (epithelial defects of the cornea that fail to heal),
      moderate to severe dry eye syndrome, ocular surface syndrome post Laser In Situ
      Keratomileusis (LASIK), and for surface reconstruction after corneal perforation
      associated with amniotic membrane transplantation. Preparation of E-PRP in the
      two available formulations, eyedrops and clot, is inexpensive and easy although
      it requires following strict sterility conditions using sterile and disposable
      materials and operating inside a laminar flow hood. No serious adverse effects
      have been described with the use of these products, and it is generally well
      tolerated. In summary, Platelet enriched plasma in the form obtained in
      ophthalmology, E-PRP, is a reliable and effective therapeutic tool to enhance
      epithelial wound healing in ocular surface disease.

PMID- 21740370
TI  - Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and
      platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 2: Bone graft,
      implant and reconstructive surgery.
AB  - Platelet concentrates for surgical use are innovative tools of regenerative
      medicine, and were widely tested in oral and maxillofacial surgery.
      Unfortunately, the literature on the topic is contradictory and the published
      data are difficult to sort and interpret. In bone graft, implant and
      reconstructive surgery, the literature is particularly dense about the use of the
      various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP)
      or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet
      Rich Fibrin (PRF) subfamilies. In this second article, we describe and discuss
      the current published knowledge about the use of PRP and PRF during implant
      placement (particularly as surface treatment for the stimulation of
      osseointegration), the treatment of peri-implant bone defects (after peri
      implantitis, during implantation in an insufficient bone volume or during
      immediate post-extraction or post-avulsion implantation), the sinuslift
      procedures and various complex implant-supported treatments. Other potential
      applications of the platelet concentrates are also highlighted in maxillofacial
      reconstructive surgery, for the treatment of patients using bisphosphonates,
      anticoagulants or with post-tumoral irradiated maxilla. Finally, we particularly
      insist on the perspectives in this field, through the description and
      illustration of the use of L-PRF (Leukocyte- and Platelet-Rich Fibrin) clots and
      membranes during the regeneration of peri-implant bone defects, during the sinus
      lift procedure and during complex implant-supported rehabilitations. The use of L
      PRF allowed to define a new therapeutic concept called the Natural Bone
      Regeneration (NBR) for the reconstruction of the alveolar ridges at the gingival
      and bone levels. As it is illustrated in this article, the NBR principles allow
      to push away some technical limits of global implant-supported rehabilitations,
      particularly when combined with other powerful biotechnological tools:
      metronidazole solution, adequate bone substitutes and improved implant designs
      and surfaces (for example here AstraTech Osseospeed or Intra-Lock Ossean
      implants). As a general conclusion, we are currently living a transition period
      in the use of PRP and PRF in oral and maxillofacial surgery. PRPs failed to prove
      strong strategic advantages that could justify their use in daily practice, and
      the use of most PRP techniques will probably be limited to some very specific
      applications where satisfactory results have been reached. Only a few simple,
      inexpensive and efficient techniques such as the L-PRF will continue to develop
      in oral and maxillofacial surgery in the next years. This natural evolution
      illustrates that clinical sciences need concrete and practical solutions, and not
      hypothetical benefits. The history of platelet concentrates in oral and
      maxillofacial surgery finally demonstrates also how the techniques evolve and
      sometimes promote the definition of new therapeutical concepts and clinical
      protocols in the today's era of regenerative medicine.

PMID- 21740371
TI  - Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and
      platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 1: Periodontal
      and dentoalveolar surgery.
AB  - Platelet concentrates for surgical use are innovative tools of regenerative
      medicine, and were widely tested in oral and maxillofacial surgery.
      Unfortunately, the literature on the topic is contradictory and the published
      data are difficult to sort and interpret. In periodontology and dentoalveolar
      surgery, the literature is particularly dense about the use of the various forms
      of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte-
      and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin
      (PRF) subfamilies. In this first article, we describe and discuss the current
      published knowledge about the use of PRP and PRF during tooth avulsion or
      extraction, mucogingival surgery, Guided Tissue Regeneration (GTR) or bone
      filling of periodontal intrabony defects, and regeneration of alveolar ridges
      using Guided Bone Regeneration (GBR), in a comprehensive way and in order to
      avoid the traps of a confusing literature and to highlight the underlying
      universal mechanisms of these products. Finally, we particularly insist on the
      perspectives in this field, through the description and illustration of the
      systematic use of L-PRF (Leukocyte- and Platelet- Rich Fibrin) clots and
      membranes during tooth avulsion, cyst exeresis or the treatment of gingival
      recessions by root coverage. The use of L-PRF also allowed to define new
      therapeutic principles: NTR (Natural Tissue Regeneration) for the treatment of
      periodontal intrabony lesions and Natural Bone Regeneration (NBR) for the
      reconstruction of the alveolar ridges. In periodontology, this field of research
      will soon find his golden age by the development of user-friendly platelet
      concentrate procedures, and the definition of new efficient concepts and clinical
      protocols.

PMID- 21740372
TI  - Leukocyte- and platelet-rich fibrin (L-PRF) for long-term delivery of growth
      factor in rotator cuff repair: review, preliminary results and future directions.
AB  - Surgical repair of the rotator cuff repair is one of the most common procedures
      in orthopedic surgery. Despite it being the focus of much research, the
      physiological tendon-bone insertion is not recreated following repair and there
      is an anatomic non-healing rate of up to 94%. During the healing phase, several
      growth factors are upregulated that induce cellular proliferation and matrix
      deposition. Subsequently, this provisional matrix is replaced by the definitive
      matrix. Leukocyte- and platelet-rich fibrin (L-PRF) contain growth factors and
      has a stable dense fibrin matrix. Therefore, use of LPRF in rotator cuff repair
      is theoretically attractive. The aim of the present study was to determine 1) the
      optimal protocol to achieve the highest leukocyte content; 2) whether L-PRF
      releases growth factors in a sustained manner over 28 days; 3) whether
      standard/gelatinous or dry/compressed matrix preparation methods result in higher
      growth factor concentrations. 1) The standard L-PRF centrifugation protocol with
      400 x g showed the highest concentration of platelets and leukocytes. 2) The L
      PRF clots cultured in medium showed a continuous slow release with an increase in
      the absolute release of growth factors TGF-beta1, VEGF and MPO in the first 7
      days, and for IGF1, PDGF-AB and platelet activity (PF4=CXCL4) in the first 8
      hours, followed by a decrease to close to zero at 28 days. Significantly higher
      levels of growth factor were expressed relative to the control values of normal
      blood at each culture time point. 3) Except for MPO and the TGFbeta-1, there was
      always a tendency towards higher release of growth factors (i.e., CXCL4, IGF-1,
      PDGF-AB, and VEGF) in the standard/gelatinous- compared to the dry/compressed
      group. L-PRF in its optimal standard/gelatinous-type matrix can store and deliver
      locally specific healing growth factors for up to 28 days and may be a useful
      adjunct in rotator cuff repair.

PMID- 21740373
TI  - Sports medicine applications of platelet rich plasma.
AB  - Platelet rich plasma (PRP) is a powerful new biologic tool in sports medicine.
      PRP is a fraction of autologous whole blood containing and increased number of
      platelets and a wide variety of cytokines such as platelet derived growth factor
      (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor
      beta-1 (TGF-B1), fibroblast growth factor (FGF), Insulin-like growth factor-1
      (IGF-1) among many others. Worldwide interest in this biologic technology has
      recently risen sharply. Basic science and preclinical data support the use of PRP
      for a variety of sports related injuries and disorders. The published, peer
      reviewed, human data on PRP is limited. Although the scientific evaluation of
      clinical efficacy is in the early stages, elite and recreational athletes already
      use PRP in the treatment of sports related injuries. Many questions remain to be
      answered regarding the use of PRP including optimal formulation, including of
      leukocytes, dosage and rehabilitation protocols. In this review, a classification
      for platelet rich plasma is proposed and the in-vitro, preclinical and human
      investigations of PRP applications in sports medicine will be reviewed as well as
      a discussion of rehabilitation after a PRP procedure. The regulation of PRP by
      the World Anti-Doping Agency will also be discussed. PRP is a promising
      technology in sports medicine; however, it will require more vigorous study in
      order to better understand how to apply it most effectively.

PMID- 21740374
TI  - Applications of leukocyte- and platelet-rich plasma (L-PRP) in trauma surgery.
AB  - Leukocyte- and platelet-rich plasma (L-PRP) contains high concentrations of
      platelet, leukocytes and other bioactivities, which play an prominent role in
      both bone and soft tissue healing processes. Large numbers of studies provide
      evidence for application of L-PRP in experiments and clinical practice. It has
      been identified to improve cellular chemotaxis, proliferation and
      differentiation, angiogenesis, and production of extracellular matrix, but also
      responsible for stimulating defense mechanisms against infections. L-PRP is now
      playing an increasing role in the management of patients with traumatic injuries.
      However, most studies are only anecdotal or case reports, and then larger
      controlled studies are needed. This article introduces the reader to L-PRP
      properties and L-PRP applications in trauma surgery, including applications of L
      PRP in bone healing, acute soft tissue wound healing, and repairing of acute
      muscle, tendon, ligament, nerve and cartilage injury caused by trauma.

PMID- 21740375
TI  - Is the use of autologous platelet-rich plasma gels in gynecologic, cardiac, and
      general, reconstructive surgery beneficial?
AB  - Tissue repair at wound sites begins with clot formation, and subsequently
      platelet degranulation with the release of platelet growth factors, which are
      necessary and well-regulated processes to achieve wound healing. Platelet-derived
      growth factors are biologically active substances that enhance tissue repair
      mechanisms, such as chemotaxis, cell proliferation, angiogenesis, extracellular
      matrix deposition, and remodeling. This review describes the biological
      background and results on the topical use of autologous platelet-rich plasma and
      platelet gel in gynecologic, cardiac, and general surgical procedures, including
      chronic wound management and soft-tissue injuries.

PMID- 21740376
TI  - The role of leukocytes from L-PRP/L-PRF in wound healing and immune defense: new
      perspectives.
AB  - Platelet concentrates for topical use are innovative tools of regenerative
      medicine and their effects in various therapeutical situations are hotly debated.
      Unfortunately, this field of research mainly focused on the platelet growth
      factors, and the fibrin architecture and the leukocyte content of these products
      are too often neglected. In the four families of platelet concentrates, 2
      families contain significant concentrations of leukocytes: L-PRP (Leukocyte- and
      Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). The
      presence of leukocytes has a great impact on the biology of these products, not
      only because of their immune and antibacterial properties, but also because they
      are turntables of the wound healing process and the local factor regulation. In
      this article, the various kinds of leukocytes present in a platelet concentrate
      are described (particularly the various populations of granulocytes and
      lymphocytes), and we insist on the large diversity of factors and pathways that
      these cells can use to defend the wound site against infections and to regulate
      the healing process. Finally, the impact of these cells in the healing properties
      of the L-PRP and L-PRF is also discussed: if antimicrobial properties were
      already pointed out, effects in the regulation of cell proliferation and
      differentiation were also hypothesized. Leukocytes are key actors of many
      platelet concentrates, and a better understanding of their effects is an
      important issue for the development of these technologies.

PMID- 21740377
TI  - Do the fibrin architecture and leukocyte content influence the growth factor
      release of platelet concentrates? An evidence-based answer comparing a pure
      platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L
      PRF).
AB  - Platelet concentrates for surgical use are tools of regenerative medicine
      designed for the local release of platelet growth factors into a surgical or
      wounded site, in order to stimulate tissue healing or regeneration. Leukocyte
      content and fibrin architecture are 2 key characteristics of all platelet
      concentrates and allow to classify these technologies in 4 families, but very
      little is known about the impact of these 2 parameters on the intrinsic biology
      of these products. In this demonstration, we highlight some outstanding
      differences in the growth factor and matrix protein release between 2 families of
      platelet concentrate: Pure Platelet-Rich Plasma (P-PRP, here the Anitua's PRGF -
      Preparation Rich in Growth Factors - technique) and Leukocyte- and Platelet-Rich
      Fibrin (L-PRF, here the Choukroun's method). These 2 families are the extreme
      opposites in terms of fibrin architecture and leukocyte content. The slow release
      of 3 key growth factors (Transforming Growth Factor beta1 (TGFbeta1), Platelet
      Derived Growth Factor AB (PDGF-AB) and Vascular Endothelial Growth Factor (VEGF))
      and matrix proteins (fibronectin, vitronectin and thrombospondin-1) from the L
      PRF and P-PRP gel membranes in culture medium is described and discussed. During
      7 days, the L-PRF membranes slowly release significantly larger amounts of all
      these molecules than the P-PRP gel membranes, and the 2 products display
      different release patterns. In both platelet concentrates, vitronectin is the
      sole molecule to be released almost completely after only 4 hours, suggesting
      that this molecule is not trapped in the fibrin matrix and not produced by the
      leukocytes. Moreover the P-PRP gel membranes completely dissolve in the culture
      medium after less than 5 days only, while the L-PRF membranes are still intact
      after 7 days. This simple demonstration shows that the polymerization and final
      architecture of the fibrin matrix considerably influence the strength and the
      growth factor trapping/release potential of the membrane. It also suggests that
      the leukocyte populations have a strong influence on the release of some growth
      factors, particularly TGFbeta1. Finally, the various platelet concentrates
      present very different biological characteristics, and an accurate definition and
      characterization of the different families of product is a key issue for a better
      understanding and comparison of the reported clinical effects of these surgical
      adjuvants.

PMID- 21740378
TI  - Platelet concentrates for topical use: bedside device and blood transfusion
      technology. Quality and versatility.
AB  - More or less after a decade of experimental and pioneering manual procedures to
      prepare platelet-rich plasma (PRP) for topical use, several portable and bedside
      devices were made available to prepare the PRP at the point-of-care. This
      technical opportunity increased the number of patients who got access to the
      treatment with autologous PRP and PRP-gel. Since topical treatment of tissue with
      PRP and PRP-gel was restricted to autologous preparation, blood transfusion
      centers that professionally prepare donor-derived platelet concentrates were not
      able to cover the overwhelming request for autologous PRP supply. Principally for
      logistic and organization reasons blood transfusion centers usually fail the
      challenge of prompt delivery of PRP to the physician over large territory.
      Nevertheless the blood bank production of platelet concentrates is associated
      with high standardization and quality controls not achievable from bedside and
      portable devices. Furthermore it easy to demonstrate that high-volume blood bank
      produced platelet concentrates are less expensive than low-volume PRP produced by
      portable and bedside devices. Taking also in consideration the ever-increasing
      safety of the blood components, the relationship between bedside device-produced
      and blood-bank-produced PRP might be reconsidered. Here we discuss this topic
      concluding that the variety of sources of PRP production is an opportunity for
      versatility and that, ultimately, versatility is an opportunity for the patient's
      care.

PMID- 21740379
TI  - In search of a consensus terminology in the field of platelet concentrates for
      surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel
      polymerization and leukocytes.
AB  - In the field of platelet concentrates for surgical use, most products are termed
      Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and
      incomplete, leading to many confusions in the scientific database. In this
      article, a panel of experts discusses this issue and proposes an accurate and
      simple terminology system for platelet concentrates for surgical use. Four main
      categories of products can be easily defined, depending on their leukocyte
      content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell
      separator PRP, Vivostat PRF or Anitua's PRGF; Leukocyteand Platelet-Rich Plasma
      (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or
      GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and
      Platelet-Rich Fibrin (L-PRF), such as Choukroun's PRF. P-PRP and L-PRP refer to
      the unactivated liquid form of these products, their activated versions being
      respectively named P-PRP gels and L-PRP gels. The purpose of this search for a
      terminology consensus is to plead for a more serious characterization of these
      products. Researchers have to be aware of the complex nature of these living
      biomaterials, in order to avoid misunderstandings and erroneous conclusions.
      Understanding the biomaterials or believing in the magic of growth factors ? From
      this choice depends the future of the field.

PMID- 21740380
TI  - Platelet-rich plasma (PRP) and Platelet-Rich Fibrin (PRF): surgical adjuvants,
      preparations for in situ regenerative medicine and tools for tissue engineering.
AB  - The recent developement of platelet concentrate for surgical use is an evolution
      of the fibrin glue technologies used since many years. The initial concept of
      these autologous preparations was to concentrate platelets and their growth
      factors in a plasma solution, and to activate it into a fibrin gel on a surgical
      site, in order to improve local healing. These platelet suspensions were often
      called Platelet-Rich Plasma (PRP) like the platelet concentrate used in
      transfusion medicine, but many different technologies have in fact been
      developed; some of them are even no more platelet suspensions, but solid fibrin
      based biomaterials called Platelet-Rich Fibrin (PRF). These various technologies
      were tested in many different clinical fields, particularly oral and
      maxillofacial surgery, Ear-Nose-Throat surgery, plastic surgery, orthopaedic
      surgery, sports medicine, gynecologic and cardiovascular surgery and
      ophthalmology. This field of research unfortunately suffers from the lack of a
      proper accurate terminology and the associated misunderstandings, and the
      literature on the topic is quite contradictory. Indeed, the effects of these
      preparations cannot be limited to their growth factor content: these products
      associate many actors of healing in synergy, such as leukocytes, fibrin matrix,
      and circulating progenitor cells, and are in fact as complex as blood itself. If
      platelet concentrates were first used as surgical adjuvants for the stimulation
      of healing (as fibrin glues enriched with growth factors), many applications for
      in situ regenerative medicine and tissue engineering were developed and offer a
      great potential. However, the future of this field is first dependent on his
      coherence and scientific clarity. The objectives of this article is to introduce
      the main definitions, problematics and perspectives that are described in this
      special issue of Current Pharmaceutical Biotechnology about platelet
      concentrates.

PMID- 21740381
TI  - RNA interference and amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a debilitating neuro-degenerative disorder
      characterized by progressive loss of motor neurons. The etiology and molecular
      pathogenesis of cell death in most sub-types of the disease are largely unknown.
      The best documented cause of moto-neuron degeneration is the mutation in the
      superoxide dismutase-1 (SOD1) gene, which occurs in 10% of the familial forms of
      ALS. Discovery of RNA interference (RNAi), which plays an important role in the
      regulation of gene expression, has proven to be a powerful tool to study the
      pathogenesis and to develop innovative treatment options for hereditary diseases,
      including familial variants of ALS. This review summarizes current research
      advances in RNAi in relation to ALS.

PMID- 21740382
TI  - An expanded, unified substrate recognition site map for mammalian cytochrome
      P450s: analysis of molecular interactions between 15 mammalian CYP450 isoforms
      and 868 substrates.
AB  - The original map of mammalian cytochrome P450 (CYP450) residues involved in
      substrate recognition was prepared for the CYP2 family by Gotoh in 1992 by manual
      alignment of mammalian CYP450 residues with substrate recognition site (SRS)
      residues manually delimited from a bacterial cytochrome P450-substrate complex.
      Using modern structural bioinformatics tools, we have identified CYP450-ligand
      interactions in mammalian complexes to create a "X-ray structures" SRS map. In a
      parallel approach, we have built a "docking" SRS map by successful docking of 868
      known substrates of 10 mammalian CYP450 isoforms and analysis of contacts made in
      docking solutions. We subsequently combined these maps to create a unified
      description of SRSs. The new map largely agrees with the original map by Gotoh
      with the six original SRS regions appearing in similar locations along the CYP450
      sequence as in Gotoh's map. However, important differences also occur: Two new
      SRS regions appear before SRS1 and we have assigned them as SRS1'a and SRS1'b;
      SRS1 is much bigger in our map than in Gotoh's (49 aligned positions versus 28);
      & SRS2 and SRS3 are co-joined in our map to give a single large SRS region (60
      aligned positions) we have designated as SRS(2,3), in contrast to the 9 and 10
      aligned positions individually covered by SRS2 and SRS3 respectively in Gotoh's
      original map. These differences result in the SRS zone covering 33 % of the
      mammalian CYP450 sequence in our map as opposed to 16 % in Gotoh's map.

PMID- 21740383
TI  - QuantiFERON-TB Gold test for screening latent tuberculosis infection in
      hemodialysis patients.
AB  - Hemodialysis patients are at increased risk of latent tuberculosis infection
      (LTBI) compared with the general population. QuantiFERON-TB Gold (QFT-G) for LTBI
      detection is more promising than tuberculin skin test (TST) in hemodialysis
      patients. The aim of this study is to determine whether the QFT-G is more
      sensitive than the TST in hemodialysis patients in LTBI. Eighty nine hemodialysis
      patients were evaluated for latent tuberculosis infection with the TST and QFT-G.
      Blood was obtained for QFT-G, and then TST was administered to all patients.
      Demographic information, laboratory tests, chest radiography results and BCG
      vaccination status were collected on standardized patient medical files. Forty
      patients had positive QFT-G results. 56 patients had TST induration above 5 mm,
      28 patients above 10 mm. 61 patients had BCG vaccination scar. Statistically
      significant correlation was detected between TST and QFT-G (p< 0.05). In the BCG
      non-vaccinated subgroup, TST was positive in 8 (29%) patients and the QFT-G was
      positive in 11 (39%). Among the 21 non vaccinated patients with results for both
      tests, the concordance between the TST and QFT-G was 82%, k= 0.61, p= 0.001. We
      found good agreement between the TST and QFT-G test for LTBI in non vaccinated
      hemodialysis patients, whereas we found poor agreement in vaccinated patients.
      Because BCG vaccination is widely used in our country, the QFT-G test might be
      more useful for the diagnosis of LTBI than TST in hemodialysis patients who are
      suspected to have LTBI.

PMID- 21740384
TI  - [The treatment results of retreatment pulmonary tuberculosis patients in our
      clinic].
AB  - 164 human immunodeficiency virus (HIV) seronegative pulmonary tuberculosis cases
      treated in our clinic between January 1997 to December 2005 and included in
      category two treatment group were evaluated retrospectively. All the cases were
      male. The mean age was 43.72 +/- 12.73 years. The mean duration of disease was
      3.96 +/- 4.80 years. The patients had used mean 4.62 +/- 0.86 types of drugs. The
      patients were hospitalized for mean 100.54 +/- 67.43 days. 23 (14%) patients were
      defined as treatment failure. 42 (25.6%) patients were relapse and 99 (60.4%)
      were defaulter. Mean time of conversion was 2.62 +/- 1.84 months. Conversion rate
      was higher in relapse cases (76.2%) compared with treatment failure (56.5%) and
      defaulter (57.6%). In 140 patients, resistance tests were performed. 73 (52.1%)
      patients had any drug resistance. 45 (32.1%) patients had multidrug resistance.
      Among all the patients, 7 (4.3%) patients had died. 48 (29.3%) patients
      defaulted. 33 (20.1%) had treatment failure. 76 (46.3%) had cured. The cure rate
      was 65.5% in patients who were in control. 36.4% of defaulters were out of
      control. This rate was significantly higher than relapse and treatment failure
      cases (p= 0.014). Cure rate in defaulters (38.4%) were significantly lower than
      relapses (61.9%) and treatment failures (52.2%). There was a significant
      relationship between any drug resistance and cure and conversion. There was also
      a significant relationship between positive second and third ARB and culture and
      treatment success. As a result, a chance to retreatment regimen can be given in
      relapses and treatment failures before deciding minor drug therapy because they
      have higher cure rates than defaulters. Defaulters are hard to cure. They have
      the tendency to default again and they have higher resistance rates. The multi
      drug resistance rate in all patients was about 32% and 46.7% of these have cured
      with retreatment regimen. Bacteriological follow up of treatment outcome is
      effective in management of therapy.

PMID- 21740385
TI  - Quality of life, depression and anxiety in young male patients with silicosis due
      to denim sandblasting.
AB  - The aim of this study was to estimate the quality of life, depression and anxiety
      in patients with silicosis due to denim sandblasting. This study was conducted on
      50 young male patients with silicosis and 30 controls. A socio-demographic data
      form, Short Form-36 (SF-36), the Beck depression inventory (BDI) and the Beck
      anxiety inventory (BAI) were used to determine quality of life, depression and
      anxiety. The mean scores of SF-36, BDI and BAI were higher in the patients than
      in the controls. Correlation analysis revealed a strong negative correlation
      between all scales of SF-36 and BDI scores. Additionally, there was strong
      negative correlation between five scales of SF-36 and BAI scores. We suggest that
      silicosis might be detrimental to the quality of life and increase depression and
      anxiety in patients with silicosis due to denim sandblasting.

PMID- 21740386
TI  - Assessment of smoking behaviors of 2509 Turkish university students and its
      correlates: a cross-sectional study.
AB  - The aim of our study is to determine smoking behavior and its correlates among
      the faculty of education students. 2509 students, out of 3200, participated in
      the smoking questionnaire survey in the Faculty of Education of Celal Bayar
      University, in Manisa, Turkey at the beginning of 2007 educational year. General
      smoking percentage in school was 45.9%. Regarding daily smoked packet numbers,
      186 (16.2%) students smoked less than a packet per day, 330 (28.6%) students
      between half and one packet, and 636 (55.2%) students more than one packet per
      day. Monthly familial income found inversely related with smoking (p= 0.003).
      According to Linear Regression Analysis, drinking behavior could be guessed by
      smoking behavior (r= 0.081) so that all of smokers had drunk also. Our study
      indicates also that the starting age to smoking has decreased to as low as 10
      years. In past 10 years while smoking prevalence in western countries decreased,
      it is increased in developing countries. In a Slovakian study, smoking prevalence
      was 21.6%, in French 34.6% and in Israeli 24.1%. Therefore, more education on the
      burdens of smoking must be given to university students.

PMID- 21740387
TI  - [The assessment of knowledge about recent tobacco law number 5727 among our
      university students, academic and administrative staff].
AB  - In this study we investigated the level of knowledge and ideas of the university
      students and staff, about the last stage of Tobacco Law No. 5727, which came into
      force on 19 July 2009 in our country. This is descriptive questionnaire survey.
      Study's universe was consisting of the students 2009-2010 academic year studying
      in our universities and academic and administrative staff. A total of 2271 people
      were included the study. In our study, smoking prevalence was 21.3%. The
      prevalence for narghile smoking as 4.8% was the highest among students. 94.9% of
      participants thought that passive smoking increased the risk for human health.
      Asked whether the banned places, the most correct answers were; the school
      (97.0%), bank branches (96.3%) and hospitals (96.2%) as the most incorrect
      answers were; in the garden of hospital (55.7%), garden of private education
      (53.4%) and the school playground (46.1%). 87.6% of the participants were
      supporting the new tobacco law. 61.3% of smokers were supporting the law (p=
      0.000). 54.3% of narghile-smokers support the law, and this rate was lower than
      cigarette smokers. Overall, tobacco law is known and supported between our
      students and staff. More information and supervision should be given about the
      banned places like school garden and private course gardens which were the high
      rate of false knowledge. The support to law among students is lower than staff.
      Similarly narghile use among students is often more. The community should be
      informed also about the other tobacco products.

PMID- 21740388
TI  - [Smoking prevalence in Kocaeli].
AB  - A questionnaire was performed in order to determine smoking prevalence in the
      target population just before the initiation of a social responsibility project
      which is aimed to increase the smoking cessation rates in Kocaeli. The sample
      selection was made based on population numbers in 12 town of Kocaeli city and
      smoking habits of population over the age of 18 were evaluated by a questionnaire
      survey by phone. There was 2721 person included in the study. The overall
      prevalence of active smokers was 32.3% (n= 902) and ex-smokers was 21.5% (n=
      587). There was no statistical significance of smoking prevalence among towns
      except the lower smoking rates in Gebze (25.7%). The percentage of the current
      smokers was 42.5% in male population which was significantly higher than females
      (21.8%). The highest smoking prevalence was found between the ages of 35-44
      (41.2%) while the lowest prevalence was observed in the subjects older than 55
      years (19.8%). The mean age for smoking initiation was 19 years (17-20) and daily
      cigarette consumption was 17 sticks. Previous attempts for quitting smoking were
      found in 67.7% of current smokers. The mean number of smoking cessation attempts
      was 3 times and the mean duration of cessation was 5 months. The most common
      reason for smoking cessation was health issues. Eighty percent of cases harnessed
      their willpower to stop smoking while only 5% of them received medical treatment.
      It is suggested that determination of demographic features of the smokers might
      constitute a corner stone for smoking cessation projects.

PMID- 21740389
TI  - [Comparison of non-invasive mechanical ventilation with helmet or face mask in
      patients with acute exacerbation of chronic obstructive pulmonary disease].
AB  - Exacerbation of chronic obstructive pulmonary disease (COPD) is one of the
      frequent causes of acute respiratory failure. In our study, we aimed to compare
      helmet with face mask in noninvasive mechanical ventilation (NIMV) on patients
      who had acute respiratory failure because of exacerbation of COPD in intensive
      care unit (ICU). Thirty patients, taken into ICU for exacerbation of COPD, were
      included in the study. Patients were divided into two groups as face mask group
      (Group Y) and helmet group (Group H). Appropriate mechanical ventilation settings
      were recorded after the starting period and NIMV was applied to patients
      continuously for two hours with these settings. Respiratory frequency (f), blood
      gas (PaO(2), PaCO(2), PH) and PaO(2)/FiO(2) values and hemodynamic data of all
      patients were recorded periodically. Compliance of patients were evaluated with
      patient tolerance scale (PTS). Duration of stay of the patients in ICU and
      complications were also noted. Demographic characteristics of patients,
      mechanical ventilator settings and hemodynamic data of the patients in the two
      groups were found to be similar (p>0.05). Frequency values measured during NIMV
      are also similar at all measurement times (p>0.05). It was determined that there
      was a remarkable decrease in respiratory frequency, in both groups after the
      application of NIMV (p< 0.001). There was no difference with respect to PaO(2),
      PH and PaO(2)/FiO(2) values at all measurement times, between groups (p> 0.05).
      PaCO(2) values in the beginning were similar in both groups but PaCO(2) measured
      at other measurement times for group H were statistically higher compared to the
      other group (p< 0.05). PTC score measured at during NIMV in group H were
      remarkably higher (p< 0.05). Helmet developed as an alternative to face mask has
      a better patient tolerance and accordingly in increases success rate in NIMV. But
      it must be keeping mind that the decrease in PaCO(2) value is slow with helmet.

PMID- 21740390
TI  - Conventional vs. endobronchial ultrasound-guided transbronchial needle aspiration
      in the diagnosis of mediastinal lymphadenopathies.
AB  - The aim of this study was to determine whether or not radial probe endobronchial
      ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is superior to
      conventional TBNA in the diagnosis of mediastinal lymphadenopathies in routine
      clinical practice. Consecutive patients, who were referred for TBNA, were
      randomized to conventional TBNA and EBUS-guided TBNA groups. Patients were also
      grouped according to the anatomic location of the pathologic lymph nodes to
      evaluate if there was a difference in the diagnostic yield with respect to lymph
      node station. Patients with subcarinal lymph nodes were designated as group A and
      patients with lymph nodes at station 2 (upper paratracheal), 3 (prevascular and
      retrotracheal), and 4 (lower paratracheal) were designated as group B. A 21-G
      aspiration needle was used during the procedure. Sixty patients with a mean age
      of 56.15 +/- 15.32 years were included in the study. Thirty patients each
      underwent EBUS-TBNA and conventional TBNA. The overall diagnostic yield of
      conventional TBNA was 33.3% (10/30), while EBUS-TBNA had a yield of 66.7% (20/30;
      p= 0.010). In patients with subcarinal lymph nodes, the yield of conventional
      TBNA was 33.3% (4/12) compared to 62.5% (5/8) in the EBUS-guided group (p=
      0.362). In patients with mediastinal lymph nodes other than subcarinal lymph
      nodes, EBUS-TBNA had a significantly higher yield compared to conventional TBNA
      [33.3% (6/18) vs. 68.2% (15/22) for conventional and EBUS-TBNA groups,
      respectively; p= 0.028]. In conclusion, the diagnostic yield of EBUS-TBNA was
      superior to the yield of conventional TBNA at stations other than subcarinal
      region. We suggest that EBUS is a useful tool to guide TBNA in the evaluation of
      mediastinal lymph nodes.

PMID- 21740391
TI  - Characteristics of children with positive tuberculin skin test.
AB  - The aim of the study was to define the characteristics of children with latent
      tuberculosis diagnosed with positive tuberculin skin test (TST) and evaluate
      potential risk factors in children with positive TST. Children followed with the
      diagnosis of latent tuberculosis infection were included in the study
      retrospectively. Demographic characteristics of patients including history of
      atopy, respiratory infections, family history of tuberculosis and atopy, number
      of BCG vaccinations, findings of physical examination and laboratory data were
      extracted from patient's file. Eighty-one children (51 male, 30 female) who had
      positive TST were retrospectively evaluated in the study. Mean age of the
      patients was 8.00 +/- 4.00 years. Only 13 (16%) of the children had contact with
      a case who had active tuberculosis. It was shown that the age of the patients,
      number of BCG scars and BCG vaccination significantly affected TST reaction size.
      TST size was not affected with time passed after last dose of BCG vaccination,
      family history of tuberculosis, presence of TST positive case in the family,
      exposure to cigarette smoke, number of household family members and presence of
      respiratory allergic disease. The patient's age, numbers of BCG vaccination and
      BCG scars significantly affect TST results in childhood. This may cause
      difficulty in diagnosing latent tuberculosis infection and in decision of
      initiating prophylactic treatment. The results of this study may show that
      recently developed, more accurate and convenient in vitro tests that they have
      higher costs and require sophisticated laboratory, can be used to diagnose latent
      tuberculosis.

PMID- 21740392
TI  - Primary sternal tuberculosis mimicking anterior chest wall tumor: case report.
AB  - A case of a sternal mass mimicking a chest wall tumor and finally diagnosed as
      primary sternal tuberculosis is presented. Fine needle biopsy was inconclusive
      and surgery included excision and drainage of a large abscess in the soft tissues
      around the involved bone. Pathology revealed multiple granulomatous and necrotic
      lesions consistent with tuberculous osteomyelitis. On a 4-drug antituberculous
      regimen the patient is an excellent condition 6 months later.

PMID- 21740393
TI  - Spontaneous massive hemothorax secondary to chest wall chondrosarcoma: a case
      report.
AB  - We present the case of a 30-year-old man with no past history of disease or
      recent trauma, who was seen in the emergency room after developing sharp pain in
      the left hemithorax. Chest roentgenogram showed costopherenic angle blunting and
      an oval mass in the left mediastinum. A computed tomographic scan showed
      extrapleural mass with coarse calcifications and pleural effusion, confirmed by
      magnetic resonance imaging. The tumor was biopsied and removed during
      thoracotomy. The pathology reported revealed chondrosarcoma, which is a rare
      cause for a spontaneous massive hemothorax. Invasion of the intercostals vessels
      by the tumor was the probable cause of hemothorax in this patient.

PMID- 21740394
TI  - An unusual case of foreign body aspiration and review of the literature.
AB  - Tracheobronchial foreign body aspiration is a health problem that can be seen in
      all age groups, and it requires urgent diagnosis and intervention. We report a
      case of an unusual foreign body aspiration in a laryngectomized patient and we
      aim to discuss this situation according to the literature. A 72-year-old man, who
      underwent total laryngectomy 7 years ago for a squamous cell carcinoma of the
      larynx, was reported with complaint of aspiration of a silicone tracheostomy
      canula. Foreign body aspiration can present with a wide variety of symptoms.
      Although it is sometimes asymptomatic, mostly there exists cough, dispnea,
      hemoptisis and even respiratory arrest. Clinical history and radiological
      examinations are enough for the diagnose but in some cases, it is difficult to
      diagnose even by bronchoscopy. In this report, ethiology, pathogenesis, clinical
      presentation, diagnose and treatment of foreign body aspirations are discussed
      under the light of the literature. Ethiology and pathogenesis are beneficial for
      the assessment of treatment time and method. Appropriate and ontime clinical
      intervention makes the diagnosis to be easier. Treatment timing and methods are
      important to prevent the complications. Flexible bronchoscopy can be used for the
      diagnose and is preferential to remove small and fit foreign bodies. For
      children, for complicated cases and in order to remove penetrating or amorph
      shaped bodies rigit bronchoscopy should be preferred.

PMID- 21740395
TI  - [Fondaparinux treatment in heparin induced thrombocytopenia:a case report].
AB  - Heparin induced thrombocytopenia is a serious complication of heparin therapy
      that has a high levels of morbidity and mortality due to thrombotic
      complications. Heparin induced thrombocytopenia usually develops between days 5
      and 14 (inclusive) following initiation of heparin. When heparin induced
      thrombocytopenia is suspected, heparin should be discontinued and treatment with
      a direct thrombin inhibitor should be initiated. Heparin induced thrombocytopenia
      occurs more frequently with unfractionated heparin than with low molecular weight
      heparin. In this manuscript, we presented a case diagnosis with heparin induced
      thrombocytopenia who was given low molecular weight heparin for prophylaxis. We
      tried to make an overview of new treatment choices along with current literature.

PMID- 21740396
TI  - Unexplained acute respiratory distress syndrome after varicocele surgery; report
      of a case.
AB  - Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory
      failure that is associated with several clinical disorders including direct
      pulmonary injury and indirect pulmonary injury. Vascular surgical patients are at
      risk for ARDS. A 23-year old man was admitted to our respiratory intensive care
      unit with short of breath, cyanosis and agitation which was developed acutely
      after varicocele operation under epidural anesthesia lasted for one hour.
      Bupivacain, fentanyl, remifentadyl and midazolam were used for epidural
      anesthesia. Oxygen saturation was 81% while breathing oxygen at FiO(2) of 0.5.
      Arterial blood gas analysis showed hypoxemia with respiratory alkalosis with a
      PaO(2)/FiO(2) score of 100. A chest radiograph demonstrated bilateral alveolar
      opacities. Bedside echocardiography was performed which revealed no evidence of
      global hypokinesia, all the chambers were normal, left ventricular ejection
      fraction was 65%. A diagnosis of ARDS was made and the patient was initiated on
      noninvasive mechanical ventilation. He was gradually weaned off the NIMV and
      discharged after a total hospital stay of four days. We report an ARDS case due
      to unexplained etiology after varicocele operation under epidural anesthesia and
      managed successfully with noninvasive mechanical ventilation.

PMID- 21740397
TI  - [Semirigid thoracoscopy in the diagnosis of pleural effusion: first four cases in
      Turkey].
AB  - Medical thoracoscopy is a valuable tool in the management and investigation of
      pleural diseases. It has advantages when compared to conventional closed pleural
      biopsy and video-assisted thoracoscopic surgery. However, the use of this
      technique is limited in Turkey. The present report is about the first experience
      with semi-rigid thoracoscope that was implemented in our country. Four patients
      underwent medical thoracoscopy in September 2009 with the new device. All
      patients were referred due to non-diagnostic closed pleural biopsy. The use of
      the device was simple and fabulous views were obtained. All biopsy specimens of
      the 4 patients were histologically adequate. Definite diagnosis was enabled in 3
      of the 4 patients when clinical features and CT findings combined with
      thoracoscopic specimens. The design is similar to the fiberoptic bronchoscope,
      respiratory physicians can easily adapt to its use. It is also compatible with
      most video operating systems and light sources used in endoscopy suites. The
      convenient use and compatibility with most endoscopic systems are raising the
      importance of the device. However, biopsy size from semirigid thoracoscope might
      cause diagnostic difficulty when compared to rigid thoracoscope.

PMID- 21740398
TI  - [Hypersensitivity pneumonitis].
AB  - Hypersensitivity pneumonitis is an immunologically induced lung disease caused by
      repeated inhalation of agents in sensitized individuals. It may present with an
      extensive variety of clinical abnormalities depending on the nature of the
      inhaled dust and the amount of exposure, the time of exposure to the antigen and
      the immunological response of the host. In this review, we discuss the
      characteristics of hypersensitivity pneumonitis based on the available
      information from the literature.

PMID- 21740399
TI  - Beta-2 agonist discussions in asthma and a review of current data.
AB  - Current guidelines recommend inhaled steroids as the first line control
      medication in the treatment of asthma. However, many patients particularly with
      airway obstruction need bronchodilators either as a symptom reliever or control
      medication to provide relaxation of bronchiolar smooth muscles. Both short acting
      and long acting beta-2 agonists (SABA and LABA) are of particular importance
      among the bronchodilators used in asthma. Despite their well-known benefits, in
      the recent years, a growing body of publications has been published on the safety
      of LABAs. However, the increased risk reported to be related to LABA monotherapy
      was not observed in patients receiving inhaled corticosteroid as the standard
      treatment in combination with LABA. The benefits of adding LABAs to inhaled
      corticosteroid have been thoroughly documented, while the risks, including asthma
      mortality, are currently under debate. Pharmacogenetic advancements drew
      attention to a potential genetic explanation for certain side effects of these
      medications whose efficacy and safety have been proven in several studies. In
      conclusion, LABAs are effective in relieving symptoms and improving lung
      functions and safe when combined with inhaled corticosteroid in asthma; however,
      LABA monotherapy should never be administered in the absence of inhaled
      corticosteroid treatment. Asthma patients that lack control of disease despite
      adequate doses of inhaled corticosteroids need addition of a regular
      bronchodilator to their treatment regimen.

PMID- 21740400
TI  - Current review of in vivo GBM rodent models: emphasis on the CNS-1 tumour model.
AB  - GBM (glioblastoma multiforme) is a highly aggressive brain tumour with very poor
      prognosis despite multi-modalities of treatment. Furthermore, recent failure of
      targeted therapy for these tumours highlights the need of appropriate rodent
      models for preclinical studies. In this review, we highlight the most commonly
      used rodent models (U251, U86, GL261, C6, 9L and CNS-1) with a focus on the
      pathological and genetic similarities to the human disease. We end with a
      comprehensive review of the CNS-1 rodent model.

PMID- 21740401
TI  - Clinical decision making in psychiatry by psychiatrists.
AB  - OBJECTIVE: To derive an in-depth understanding of the decision-making process in
      psychiatry and to explore similarities and differences in psychiatrists' decision
      making process and the factors that may influence psychiatrists' decisions.
      METHOD: A total of 31 psychiatrists were interviewed on their approaches to
      decision making in psychiatric practice, using a semistructured interview guide.
      Framework analysis was undertaken to derive a qualitative understanding of
      decision making in psychiatry. RESULTS: The analysis generated seven main themes,
      which collectively influenced the decision-making process in psychiatry:
      information gathering, training in psychiatry, intuition and experience, evidence
      based practice, cognitive reasoning, uncontrollable factors and multidisciplinary
      team influences. CONCLUSION: No single approach to decision making emerged from
      the analysis. Approaches to decision making were influenced by the level of
      clinical experience and external pressures, such as time and treatment
      availability. Findings were consistent with dual-processing theory of decision
      making.

PMID- 21740402
TI  - The eyes are the window to the brain: reviewing oculomotor abnormalities in
      obsessive-compulsive disorder.

PMID- 21740403
TI  - A controlled trial investigating the effect of music therapy during an acute
      psychotic episode.
AB  - OBJECTIVE: To investigate the effects of music therapy, as an adjunct to
      pharmacological therapy during an acute psychotic episode. METHOD: Sixty
      participants were quasi-randomised into either a treatment or control group.
      Standardised psychological assessments [Brief Psychiatric Rating Scale (BPRS),
      Calgary Interview Guide for Depression, Nurses' Observation Scale for Inpatient
      Evaluation (NOSIE-30) and Depression Anxiety Stress Scale (DASS21)] were
      conducted before and after the sessions to determine whether there were any
      significant changes in outcomes. RESULTS: Statistically significant changes in
      BPRS scores were seen in the treatment group (n = 25) compared with the control
      group (n = 24). No significant differences were seen in the results of the
      Calgary, NOSIE-30 or DASS21 scores. Despite the treatment group, having a 9.3%
      decrease in their length of stay in hospital as opposed to the control group,
      this did not reach statistical significance. No significant differences were
      found when comparing the two groups in their doses of antipsychotic,
      benzodiazepine, mood stabilising or antidepressant medication or at the 1-month
      follow-up assessment. CONCLUSION: Most of the variables tested in our study but
      one did not point at any advances of adding music therapy to pharmacological
      treatment. The finding of improvement in Brief Psychiatric Rating Scale could be
      an indicator of music therapy as a useful adjunct to pharmacotherapy during an in
      patient hospital stay for the few patients amongst those suffering acute
      psychosis that accept to participate in music therapy.

PMID- 21740404
TI  - Proteolytic activity and expression of the 20S proteasome are increased in
      psoriasis lesional skin.
AB  - BACKGROUND: Deregulation of the proteasome pathway has been shown to be involved
      in the pathogenesis of several inflammatory disorders. To date limited
      information exists on proteasome and immunoproteasome expression and activity in
      psoriasis skin. OBJECTIVES: To investigate the potential role of proteasomes in
      the pathogenesis of psoriasis. METHODS: Thirty-six patients with psoriasis and 40
      healthy subjects were included. The protein and mRNA expression levels and
      proteolytic activity of proteasome and immunoproteasome subunits were determined
      using immunohistochemistry, quantitative polymerase chain reaction and
      fluorogenic peptide substrate in lesional and nonlesional psoriasis skin. We
      additionally measured the plasmatic proteasome (p-proteasome) levels using enzyme
      linked immunosorbent assay. RESULTS: We reveal an increased expression of
      proteasome and immunoproteasome subunits but stable mRNA levels in lesional
      psoriasis skin as compared with nonlesional psoriasis skin (n = 19), suggesting
      that proteasome and immunoproteasome expression is regulated post
      transcriptionally. This proteasome overexpression was associated with a
      significant increase of the proteasomal chymotrypsin-like activity that was
      threefold higher in lesional skin than in nonlesional skin (n = 3). p-Proteasome
      levels were enhanced in patients with psoriasis (mean +/- SEM 3960 +/- 299 ng mL(
      1) , range 1484-8987) when compared with controls (2535+/-187 ng mL(-1) , range
      654-6446, P<0.001) and were significantly higher in psoriatic arthritis (4937+/
      572 ng mL(-1) , range 2600-8987). In addition, they were correlated to the body
      surface area involved and appeared thus as a new biomarker of psoriasis severity.
      CONCLUSIONS: Altogether these results strongly suggest the involvement of the
      proteasome system in the pathogenesis of psoriasis and support the relevance of
      proteasome inhibitors in local or systemic treatment of psoriasis.

PMID- 21740405
TI  - New anticoagulants - promising and failed developments.
AB  - New direct and indirect acting factor Xa (FXa) and thrombin inhibitors are being
      developed to overcome the downsides of the conventional anticoagulants -
      unfractionated and low molecular weight heparins and vitamin K antagonists.
      Ximelagatran and idraparinux failed to demonstrate an acceptable safety profile.
      Rivaroxaban and dabigatran are approved for the post-operative prevention of
      thromboembolic complications after elective hip or knee replacement surgery;
      dabigatran is approved for the prevention of embolism in patients with atrial
      fibrillation in an increasing number of countries. Several novel indirect
      antithrombin-dependent anticoagulants as well as antithrombin-independent oral
      direct FXa and thrombin inhibitors are investigated in multiple indications for
      the prophylaxis and treatment of venous thromboembolism and the prophylaxis of
      arterial thrombotic disorders. Quality-adjusted life years costs and incremental
      cost-effectiveness ratios are relatively high at present, but may decrease after
      approval of more new anticoagulants for additional indications.

PMID- 21740406
TI  - Oral fingolimod rescues the functional deficits of synapses in experimental
      autoimmune encephalomyelitis.
AB  - BACKGROUND AND PURPOSE Alterations of glutamate-mediated synaptic transmission
      occur early during neuroinflammatory insults, and lead to degenerative neuronal
      damage in multiple sclerosis (MS) and also in experimental autoimmune
      encephalomyelitis (EAE), which is a murine model of MS. Fingolimod is an
      effective orally active agent for the treatment of MS, affecting lymphocyte
      invasion of the brain. However, it is still unclear if fingolimod can be
      neuroprotective in this disorder. EXPERIMENTAL APPROACH Using neurophysiological
      recordings and morphological evaluation of dendritic integrity, we evaluated the
      effects of oral fingolimod on the clinical score of EAE mice in order to
      determine whether the compound was associated with preservation of synaptic
      transmission. KEY RESULTS Oral fingolimod prevented and reversed the pre- and
      postsynaptic alterations of glutamate transmission in EAE mice. These effects
      were associated with a clear amelioration of the clinical deterioration seen in
      EAE mice, and with a significant inhibition of neuronal dendritic pathology.
      Fingolimod did not alter the spontaneous excitatory postsynaptic currents in
      control animals, suggesting that only the pathological processes behind the
      inflammation-induced defects in glutamate transmission were modulated by this
      compound. CONCLUSIONS AND IMPLICATIONS The beneficial effects of fingolimod on
      the clinical, synaptic and dendritic abnormalities of murine EAE might correlate
      with the neuroprotective actions of this agent, as observed in MS patients.
      LINKED ARTICLE This article is commented on by Gillingwater, pp. 858-860 of this
      issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476
      5381.2011.01612.x.

PMID- 21740407
TI  - Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by
      increasing intestinal glucose absorption and activating hepatic lipogenesis.
AB  - BACKGROUND AND PURPOSE: Pentoxifylline is in clinical trials for non-alcoholic
      fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of
      pentoxifylline were assessed in a murine model of obesity and type 2 diabetes.
      EXPERIMENTAL APPROACH: Pentoxifylline (100 mg.kg(-1) .day(-1)) was administered
      for 4 days or 3 weeks in lean and obese/diabetic ob/ob mice. Plasma lipids,
      glucose, other metabolites and relevant enzymes were measured by standard assays.
      Hepatic lipids in vivo were assessed with magnetic resonance spectroscopy and by
      histology. Hepatic extracts were also analysed with RT-PCR and Western blotting.
      KEY RESULTS: Four days of pentoxifylline treatment slightly increased liver
      lipids in ob/ob mice. After 3 weeks, pentoxifylline exacerbated fatty liver and
      plasma transaminases in ob/ob mice but did not induce liver steatosis in lean
      mice. Plasma glucose was highest in fed, but not fasted, ob/ob mice treated with
      pentoxifylline. During the first 10 min of an oral glucose tolerance test, blood
      glucose increased more rapidly in pentoxifylline-treated mice. Jejunal expression
      of glucose transporter 2 isoform was increased in pentoxifylline-treated obese
      mice. Hepatic activity of carbohydrate response element binding protein (ChREBP)
      increased after pentoxifylline in ob/ob, but not lean, mice. Hepatic expression
      of lipogenic enzymes was highest in pentoxifylline-treated ob/ob mice. However,
      pentoxifylline reduced markers of oxidative stress and inflammation in ob/ob
      liver. CONCLUSION AND IMPLICATIONS: Pentoxifylline exacerbated fatty liver in
      ob/ob mice through enhanced intestinal glucose absorption, increased postprandial
      glycaemia and activation of hepatic lipogenesis. Long-term treatment with
      pentoxifylline could worsen fatty liver in some patients with pre-existing
      hyperglycaemia.

PMID- 21740408
TI  - Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian
      adenocarcinoma cells by targeting alpha5beta1 integrin to down-regulate Akt and
      MMP-2.
AB  - BACKGROUND AND PURPOSE: As prognosis for patients with metastatic ovarian cancer
      is generally poor, advances in treatment are needed. Here, we studied the
      mechanism of action of a recombinant viral capsid protein (rVP1) and explored its
      effect against ovarian tumour growth and metastasis in vivo. EXPERIMENTAL
      APPROACH: The human ovarian cancer cell line SKOV3 and BALB/cAnN-Foxn1 female
      nude mice were used. Effects of rVP1 on the viability, invasive ability, matrix
      metalloproteinase (MMP)-2 activity and cancer cell proliferation and metastasis
      were determined by cell proliferation assay, Matrigel invasion assay, gelatin
      zymographic analysis, as well as bioluminescence imaging and immunohistological
      analysis in xenograft mouse models respectively. Levels of total and
      phosphorylated focal adhesion kinase (FAK), PKB/Akt, phosphatase and tensin
      homologue (PTEN) and glycogen synthase kinase-3beta (GSK-3beta) were detected by
      Western blotting. KEY RESULTS: rVP1 promoted apoptosis and decreased invasion of
      human ovarian cancer cells. This effect of rVP1 was accompanied by activation of
      PTEN and GSK-3beta as well as down-regulation of FAK, Akt and MMP-2. Anti
      integrin antibodies or overexpression of constitutively active Akt reversed the
      cellular effects of rVP1. Orthotopic and intraperitoneal xenograft mouse models
      demonstrated that rVP1 attenuated survival and metastasis of human ovarian cancer
      SKOV3 cell line in vivo through selective regulation of Akt and GSK-3beta
      activity as shown by bioluminescence imaging of mice and immunohistochemical
      analysis. CONCLUSION AND IMPLICATIONS: These results indicate that negative
      regulation of Akt signalling and MMP-2 by rVP1 may have the potential to suppress
      ovarian tumour growth and metastasis in vivo.

PMID- 21740409
TI  - The 5-HT3B subunit affects high-potency inhibition of 5-HT3 receptors by
      morphine.
AB  - BACKGROUND AND PURPOSE: Morphine is an antagonist at 5-HT(3) A receptors. 5-HT(3)
      and opioid receptors are expressed in many of the same neuronal pathways where
      they modulate gut motility, pain and reinforcement. There is increasing interest
      in the 5-HT3B subunit, which confers altered pharmacology to 5-HT(3) receptors.
      We investigated the mechanisms of inhibition by morphine of 5-HT(3) receptors and
      the influence of the 5-HT3B subunit. EXPERIMENTAL APPROACH: 5-HT-evoked currents
      were recorded from voltage-clamped HEK293 cells expressing human 5-HT3A subunits
      alone or in combination with 5-HT3B subunits. The affinity of morphine for the
      orthosteric site of 5-HT(3) A or 5-HT(3) AB receptors was assessed using
      radioligand binding with the antagonist [(3) H]GR65630. KEY RESULTS: When pre
      applied, morphine potently inhibited 5-HT-evoked currents mediated by 5-HT(3) A
      receptors. The 5-HT3B subunit reduced the potency of morphine fourfold and
      increased the rates of inhibition and recovery. Inhibition by pre-applied
      morphine was insurmountable by 5-HT, was voltage-independent and occurred through
      a site outside the second membrane-spanning domain. When applied simultaneously
      with 5-HT, morphine caused a lower potency, surmountable inhibition of 5-HT(3) A
      and 5-HT(3) AB receptors. Morphine also fully displaced [(3) H]GR65630 from 5
      HT(3) A and 5-HT(3) AB receptors with similar potency. CONCLUSIONS AND
      IMPLICATIONS: These findings suggest that morphine has two sites of action, a low
      affinity, competitive site and a high-affinity, non-competitive site that is not
      available when the channel is activated. The affinity of morphine for the latter
      is reduced by the 5-HT3B subunit. Our results reveal that morphine causes a high
      affinity, insurmountable and subunit-dependent inhibition of human 5-HT(3)
      receptors.

PMID- 21740410
TI  - Inhibition of matrix metalloproteinase-2 improves endothelial function and
      prevents hypertension in insulin-resistant rats.
AB  - BACKGROUND AND PURPOSE: Insulin resistance is often found to be associated with
      high blood pressure. We propose that in insulin-resistant hypertension,
      endothelial dysfunction is the consequence of increased activity of vascular MMP
      2. As MMP-2 proteolytically cleaves a number of extracellular matrix proteins, we
      hypothesized that MMP-2 impairs endothelial function by proteolytic degradation
      of endothelial NOS (eNOS) or its cofactor, heat shock protein 90 (HSP90).
      EXPERIMENTAL APPROACH: We tested our hypothesis in bovine coronary artery
      endothelial cells and fructose-fed hypertensive rats (FHR), a model of acquired
      systolic hypertension and insulin resistance. KEY RESULTS: Treatment of FHRs with
      the MMP inhibitor doxycycline, preserved endothelial function as well as
      prevented the development of hypertension, suggesting that MMPs impair
      endothelial function. Furthermore, incubating endothelial cells in vitro with a
      recombinant MMP-2 decreased NO production in a dose-dependent manner. Using
      substrate cleavage assays and immunofluorescence microscopy studies, we found
      that MMP-2 not only cleaves and degrades HSP90, an eNOS cofactor but also co
      localizes with both eNOS and HSP90 in endothelial cells, suggesting that MMPs
      functionally interact with the eNOS system. Treatment of FHRs with doxycycline
      attenuated the decrease in eNOS and HSP90 expression but did not improve insulin
      sensitivity. CONCLUSIONS AND IMPLICATIONS: Our data suggest that increased
      activity of MMP-2 in FHRs impairs endothelial function and promotes hypertension.
      Inhibition of MMP-2 could be a potential therapeutic strategy for the management
      of hypertension.

PMID- 21740411
TI  - Oxidative species increase arginase activity in endothelial cells through the
      RhoA/Rho kinase pathway.
AB  - BACKGROUND AND PURPOSE: NO produced by endothelial NOS is needed for normal
      vascular function. During diabetes, aging and hypertension, elevated levels of
      arginase can compete with NOS for available l-arginine, reducing NO and
      increasing superoxide (O(2) (.-)) production via NOS uncoupling. Elevated O(2) (.
      ) combines with NO to form peroxynitrite (ONOO(-)), further reducing NO.
      Oxidative species increase arginase activity, but the mechanism(s) involved are
      not known. Our study determined the mechanism involved in peroxynitrite and
      hydrogen peroxide-induced enhancement in endothelial arginase activity. We
      hypothesized that oxidative species increase arginase activity through PKC
      activated RhoA/Rho kinase (ROCK) pathway. EXPERIMENTAL APPROACH: Arginase
      activity/expression was analysed in bovine aortic endothelial cells (BAEC)
      treated with an ONOO(-) generator (SIN-1) or H(2) O(2). Pretreatment with
      inhibitors of Rho kinase (Y-27632) or PKC (Go6976) was used to investigate the
      mechanism involved in arginase activation. KEY RESULTS: Exposure to SIN-1 (25 uM,
      24 h) or H(2) O(2) (25 uM, 8 h) increased arginase I expression and arginase
      activity (35% and 50%, respectively), which was prevented by ROCK inhibitor, Y
      27632, PKC inhibitor, Go6976 or siRNA to p115-Rho GEF. There was an early
      activation of p115-Rho GEF (SIN-1, 2 h; H(2) O(2), 1 h) and Rho A (SIN-1, 4 h;
      H(2) O(2), 1 h) that was prevented by using the PKC inhibitor. Exposure to SIN-1
      and H(2) O(2 ) also reduced NOS activity, which was blocked by pretreatment with
      p115-RhoGEF siRNA. CONCLUSIONS AND IMPLICATIONS: Our data indicate that the
      oxidative species ONOO(-) and H(2) O(2) increase arginase activity/expression
      through PKC-mediated activation of RhoA/Rho kinase pathway.

PMID- 21740412
TI  - Hyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of
      gadodiamide.
AB  - BACKGROUND AND PURPOSE: Hyperphosphataemia is common in patients with nephrogenic
      systemic fibrosis (NSF). NSF has been linked to administration of gadolinium (Gd)
      chelates (GCs) and elevated serum phosphate levels accelerate the release of Gd
      from linear, non-ionic GCs but not macrocyclic GCs. Hence, we determined whether
      hyperphosphataemia is a cofactor or risk factor for NSF by investigating the role
      of hyperphosphataemia in renally impaired rats. EXPERIMENTAL APPROACH: Firstly,
      the clinical, pathological and bioanalytical consequences of hyperphosphataemia
      were investigated in subtotal nephrectomized (SNx) Wistar rats following i.v.
      administration of the non-ionic, linear GC gadodiamide (5 * 2.5 mmol.kg(-1) .day(
      1) ). Secondly, the effects of several GCs were compared in these high-phosphate
      diet fed rats. Total Gd concentration in skin, femur and plasma was measured by
      inductively coupled plasma mass spectrometry (ICP-MS) and free Gd(3+)  in plasma
      by liquid chromatography coupled to ICP-MS. Relaxometry was used to measure
      dissociated Gd in skin and bone. KEY RESULTS: Four out of seven SNx rats fed a
      high-phosphate diet administered gadodiamide developed macroscopic and
      microscopic (fibrotic and inflammatory) skin lesions, whereas no skin lesions
      were observed in SNx rats treated with saline, the other GCs and free ligands or
      in the normal diet, gadodiamide-treated group. Unlike the other molecules,
      gadodiamide gradually increased the r(1)  relaxivity value, consistent with its
      in vivo dissociation and release of soluble Gd. CONCLUSIONS AND IMPLICATIONS:
      Hyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of
      gadodiamide. Unlike the other GCs investigated, gadodiamide gradually dissociates
      in vivo. Our data confirm that hyperphosphataemia is a risk factor for NSF.

PMID- 21740413
TI  - Silencing of P2Y(2)  receptors reduces intraocular pressure in New Zealand
      rabbits.
AB  - BACKGROUND AND PURPOSE: P2 receptors are involved in the regulation of ocular
      physiological processes like intraocular pressure (IOP). In the present study,
      the involvement of P2Y(2)  receptors in the hypertensive effect of nucleotides
      was investigated by use of antagonists and of a siRNA designed for the P2Y(2) 
      receptor. EXPERIMENTAL APPROACH: Agonists of the P2Y(2)  receptor a as well as P2
      antagonists were applied to eyes of New Zealand rabbits, and the changes in IOP
      were followed for up to 6 h. Cloning of the P2Y(2)  receptor cDNA was done using
      a combination of degenerate reverse transcription PCR (RT-PCR) and rapid
      amplification of cDNA ends (RACE). siRNA was synthesized and tested by
      immunohistochemistry. KEY RESULTS: Single doses of 2-thioUTP, UTP-gamma-S and UTP
      increased IOP. This behaviour was concentration-dependent and partially
      antagonized by reactive blue 2. Silencing the P2Y(2)  receptor was observed in
      the ciliary body by immunohistochemistry labelling, where a reduction in the
      immunofluorescence was observed. This reduction in the expression of the P2Y(2) 
      receptor was concomitant with a reduction in IOP, which was measurable 24 h after
      treatment with the siRNA, maximal after 2 days, followed by a slow increase
      towards control values for the following 5 days. Application of the P2Y(2) 
      agonists after pretreatment of the animals with this siRNA did not produce any
      change in IOP. CONCLUSIONS AND IMPLICATIONS: P2Y(2)  receptors increase IOP in
      New Zealand rabbits. The application of a siRNA for this receptor significantly
      reduced IOP, suggesting that this technology might be used for the treatment of
      glaucoma.

PMID- 21740414
TI  - Lipocalin-2 deficiency prevents endothelial dysfunction associated with dietary
      obesity: role of cytochrome P450 2C inhibition.
AB  - BACKGROUND AND PURPOSE: Lipocalin-2 is a pro-inflammatory adipokine up-regulated
      in obese human subjects and animal models. Its circulating levels are positively
      correlated with the unfavourable lipid profiles, elevated blood pressure and
      insulin resistance index. Augmented lipocalin-2 has been found in patients with
      cardiovascular abnormalities.The present study was designed to investigate the
      role of lipocalin-2 in regulating endothelial function and vascular reactivity.
      EXPERIMENTAL APPROACH: Wild-type and lipocalin-2 knockout (Lcn2-KO) mice were fed
      with either a standard chow or a high-fat diet. Blood pressures and endothelium
      dependent relaxations/contractions were monitored at 2 week intervals. RESULTS:
      Systolic blood pressure was elevated by high-fat diet in wild-type mice but not
      in Lcn2-KO mice. Endothelial dysfunction, reflected by the impaired endothelium
      dependent relaxations to insulin and augmented endothelium-dependent contractions
      to ACh, was induced by high-fat diet in wild-type mice. In contrast, Lcn2-KO mice
      were largely protected from the deterioration of endothelial function caused by
      dietary challenges. The eNOS dimer/monomer ratio, NO bioavailability, basal and
      insulin-stimulated PKB/eNOS phosphorylation responses were higher in aortae of
      Lcn2-KO mice. Administration of lipocalin-2 attenuated endothelium-dependent
      relaxations to insulin and promoted endothelium-dependent contractions to ACh. It
      induced eNOS uncoupling and elevated COX expression in the arteries. Treatment
      with sulphaphenazole, a selective inhibitor of cytochrome P450 2C9, improved
      endothelial function in wild-type mice and blocked the effects of lipocalin-2 on
      both endothelium-dependent relaxations to insulin and endothelium-dependent
      contractions to ACh, as well as eNOS uncoupling. CONCLUSIONS: Lipocalin-2, by
      modulating cytochrome P450 2C9 activity, is critically involved in diet-induced
      endothelial dysfunction.

PMID- 21740416
TI  - Personality Assessment Inventory among patients with psychogenic seizures and
      those with epilepsy.
AB  - The Personality Assessment Inventory (PAI) is a widely used self-report
      questionnaire designed to detect and quantify dimensions of adult
      psychopathology. Previous studies that examined the ability of the PAI to
      differentiate between patients with psychogenic nonepileptic seizures (PNES) and
      those with epilepsy (EPIL) have yielded inconsistent results. We compared the
      full PAI profiles of 62 patients with PNES, 55 with EPIL, and 45 normal control
      (NC) participants to determine the diagnostic accuracy of the PAI. We also sought
      to highlight psychopathologic symptoms that may inform psychological treatment of
      patients with PNES or epilepsy. PNES and EPIL patients reported more somatic
      concerns and symptoms of anxiety and depression than did NC persons. PNES
      patients reported more unusual somatic symptoms, as well as greater physical
      symptoms of anxiety and depression than did patients with EPIL. Classification
      accuracy of the "NES Indicator" was not much better than chance, whereas the
      Conversion subscale alone had reasonable sensitivity (74%) and specificity (67%).
      Overall, the PAI demonstrated only moderate classification accuracy in an
      epilepsy monitoring unit sample. However, the inventory appears to identify
      specific psychopathological symptoms that may be targets of
      psychological/psychiatric intervention.

PMID- 21740415
TI  - Use of inotropes and vasopressor agents in critically ill patients.
AB  - Inotropes and vasopressors are biologically and clinically important compounds
      that originate from different pharmacological groups and act at some of the most
      fundamental receptor and signal transduction systems in the body. More than 20
      such agents are in common clinical use, yet few reviews of their pharmacology
      exist outside of physiology and pharmacology textbooks. Despite widespread use in
      critically ill patients, understanding of the clinical effects of these drugs in
      pathological states is poor. The purpose of this article is to describe the
      pharmacology and clinical applications of inotropic and vasopressor agents in
      critically ill patients.

PMID- 21740417
TI  - Epilepsy imaging study guideline criteria: commentary on diagnostic testing study
      guidelines and practice parameters.
AB  - Recognition of limited economic resources, as well as potential adverse effects
      of "over testing," has increased interest in "evidence-based" assessment of new
      medical technology. This creates a particular problem for evaluation and
      treatment of epilepsy, which are increasingly dependent on advanced imaging and
      electrophysiology, since there is a marked paucity of epilepsy diagnostic and
      prognostic studies that meet rigorous standards for evidence classification. The
      lack of high quality data reflects fundamental weaknesses in many imaging studies
      but also limitations in the assumptions underlying evidence classification
      schemes as they relate to epilepsy, and to the practicalities of conducting
      adequately powered studies of rapidly evolving technologies. We review the
      limitations of current guidelines and propose elements for imaging studies that
      can contribute meaningfully to the epilepsy literature.

PMID- 21740418
TI  - Supernumerary phantom limb as a rare symptom of epileptic seizures--case report
      and literature review.
AB  - Supernumerary phantom limbs, that is, the awareness of an illusory extra limb is
      a fascinating neurologic symptom that has been described in a number of
      neurologic diseases including stroke, spinal injury, and epilepsy. Herein we
      report a case of a 70-year-old male patient with new-onset focal seizures with
      left-sided supernumerary phantom arm and leg as the only seizure manifestation.
      Ictal single-photon emission computed tomography (SPECT) revealed a
      hyperperfusion in the right temporoparietal junction and allowed localization of
      the seizure-onset zone. This report is accompanied by a discussion of
      phenomenology and terminology in the context of existing literature.

PMID- 21740419
TI  - The cognitive consequence of resecting nonlesional tissues in epilepsy surgery-
      results from MRI- and histopathology-negative patients with temporal lobe
      epilepsy.
AB  - PURPOSE: Because more selective and individual versus extended standard surgery
      in the treatment of epilepsy appears to result in similar seizure outcomes, the
      issue of sparing nonlesional and hypothetically still-functioning tissues has
      become a central topic in epilepsy surgery. Within this framework we hypothesized
      that surgery in magnetic resonance imaging (MRI)- and histopathologically
      negative patients with temporal lobe epilepsy (TLE) may serve as a proof of
      principle about the negative cognitive consequences of resecting nonlesional
      tissue. METHODS: Verbal and figural memory outcomes after temporal lobe surgery
      in 15 MRI- and histopathologically negative patients (MRH-) were compared to
      those obtained in 15 MRI- and histopathologically positive patients (MRH+). In
      the MRH- group, 53% were male, 66% were resected on the left side, 13% underwent
      selective amygdalohippocampectomy, and 20% became seizure-free. MRH+ patients
      were selected from >1,000 TLE patients, and provided matched pairs in regard to
      chronological age, sex, IQ, attention performance, onset of epilepsy, side and
      type of surgery, age at surgery, and seizure outcome. Individual and combined
      standardized scores for verbal/figural memory were evaluated. KEY FINDINGS:
      Preoperatively, memory was significantly better and less frequently impaired in
      MRH- as opposed to MRH+ patients. Postoperatively, memory losses in MRH- were
      more severe as opposed to MRH+ patients who did not change, on average. Losses in
      individual test parameters were seen in between 27% and 80% in MRH- patients as
      compared to between 13% and 47% in MRH+ patients. After surgery, outcomes for
      both groups were at comparably poor performance levels. SIGNIFICANCE:
      Preoperative group differences in memory and the finding that, after surgery,
      both groups had comparably poor performance levels indicate a major relevance of
      morphologic structural lesions for memory impairment in TLE. The findings in
      particular confirm the negative impact of the resection of nonlesional functional
      tissue for cognitive surgical outcome. Absence of MRI lesion and unimpaired
      memory appear as significant risk factors for postoperative memory loss in
      temporal lobe surgery.

PMID- 21740420
TI  - Focal cortical dysplasia type IIb: completeness of cortical, not subcortical,
      resection is necessary for seizure freedom.
AB  - PURPOSE: Focal cortical dysplasia type IIb (FCD IIb) lesions are highly
      epileptogenic and frequently cause pharmacoresistant epilepsy. Complete surgical
      resection leads to seizure freedom in most cases. However, the term "complete"
      resection is controversial with regard to the necessity of performing resections
      of the subcortical zone, which is frequently seen in these lesions on magnetic
      resonance imaging (MRI). METHODS: We retrospectively analyzed 50 epilepsy
      patients with histologically proven FCD IIb. The extent of surgical resection was
      determined by SPM5-based coregistration of the preoperative and postoperative MRI
      scans. Postoperative outcome was analyzed with regard to (1) the completeness of
      the resection of the cortical abnormality and (2) the completeness of the
      resection of the subcortical abnormality. KEY FINDINGS: Complete resection of the
      cortical abnormality led to postoperative seizure freedom (Engel class Ia) in 34
      of 37 patients (92%), whereas incomplete cortical resection achieved this in only
      one of 13 patients (8%, p < 0.001). Among the patients with complete cortical
      resection, 36 had FCDs with a subcortical hyperintensity according to MRI. In
      this group, complete resection of the subcortical abnormality did not result in a
      better postoperative outcome than incomplete resection (90% vs. 93% for Engel
      class Ia, n.s.). SIGNIFICANCE: Complete resection of the MRI-documented cortical
      abnormality in FCD IIb is crucial for a favorable postoperative outcome. However,
      resection of the subcortical hyperintense zone is not essential for seizure
      freedom. Therefore, sparing of the subcortical white matter may reduce the
      surgical risk of encroaching on relevant fiber tracts. In addition, these
      findings give an interesting insight into the epileptogenic propensity of
      different parts of these lesions.

PMID- 21740421
TI  - Electrical stimulation-induced seizures in rats: a "dose-response" study on
      resultant neurodegeneration.
AB  - Perforant pathway stimulation (PPS) is used to study temporal lobe epilepsy in
      rodents. High-frequency PPS induces acute seizures, which can lead to neuron
      death and spontaneous epilepsy. However, the minimum duration of PPS that induces
      neurodegeneration in naive rodents is unknown. Freely moving Sprague-Dawley rats
      received one episode of continuous, bilateral PPS (range 1-180 min). Simultaneous
      recording from the hippocampal granule cell layer confirmed the presence of
      epileptiform activity and showed precisely when seizure activity was terminated
      by anesthesia. Fluoro-Jade B staining, 1-7 days after PPS, determined neuronal
      degeneration. Thirty-five minutes of continuous PPS produced no apparent neuron
      death anywhere in the brain. The minimum duration that caused neurodegeneration,
      which was confined to the dentate hilus, was 40 min. These data indicate that, in
      freely moving naive rats: (1) 40 min of PPS-induced seizure activity is the
      threshold for brain cell death, and (2) dentate hilar neurons are the most
      vulnerable to PPS. Further studies are warranted to determine the threshold of
      epileptogenic neurodegeneration.

PMID- 21740422
TI  - Iatrogenic seizures during intracranial EEG monitoring.
AB  - Cerebral edema with declining neurologic status is a known complication of
      intracranial electroencephalography (EEG) monitoring. The frequency and
      consequences of iatrogenic edema that is not clinically evident are presently
      poorly defined. We investigated the potential for intracranial electrodes to
      cause subclinical cerebral edema, and for such edema to cause iatrogenic
      seizures. In a retrospective review of 33 adults who had head magnetic resonance
      imaging (MRI) while undergoing epilepsy surgery evaluation with intracranial EEG,
      28% (6 of 21) depth electrode implantations had subclinical vasogenic edema. Of
      these, 50% (3 of 6) had nonhabitual electrographic seizures that appear to result
      from iatrogenic edema. No long-term adverse sequelae were noted, however, if
      unrecognized, iatrogenic seizures could lead to unnecessary exclusion from
      definitive surgical intervention for refractory epilepsy.

PMID- 21740423
TI  - Movement of water infiltrated from a recharge basin to wells.
AB  - Local surface water and stormflow were infiltrated intermittently from a 40-ha
      basin between September 2003 and September 2007 to determine the feasibility of
      recharging alluvial aquifers pumped for public supply, near Stockton, California.
      Infiltration of water produced a pressure response that propagated through
      unconsolidated alluvial-fan deposits to 125 m below land surface (bls) in 5 d and
      through deeper, more consolidated alluvial deposits to 194 m bls in 25 d,
      resulting in increased water levels in nearby monitoring wells. The top of the
      saturated zone near the basin fluctuates seasonally from depths of about 15 to 20
      m. Since the start of recharge, water infiltrated from the basin has reached
      depths as great as 165 m bls. On the basis of sulfur hexafluoride tracer test
      data, basin water moved downward through the saturated alluvial deposits until
      reaching more permeable zones about 110 m bls. Once reaching these permeable
      zones, water moved rapidly to nearby pumping wells at rates as high as 13 m/d.
      Flow to wells through highly permeable material was confirmed on the basis of
      flowmeter logging, and simulated numerically using a two-dimensional radial
      groundwater flow model. Arsenic concentrations increased slightly as a result of
      recharge from 2 to 6 ug/L immediately below the basin. Although few water-quality
      issues were identified during sample collection, high groundwater velocities and
      short travel times to nearby wells may have implications for groundwater
      management at this and at other sites in heterogeneous alluvial aquifers.

PMID- 21740424
TI  - Number and location of venous valves within the popliteal and femoral veins: a
      review of the literature.
AB  - Although deep venous insufficiency is common and important, the anatomy of deep
      vein valves is poorly understood. The aim of this study was to investigate the
      location, number and consistency of venous valves in the femoral and popliteal
      veins in normal subjects. A detailed literature search of PubMed was performed.
      Abstracts and selected full text articles were scrutinised and relevant studies
      published between 1949 and 2010 reporting anatomical details of deep vein valves
      were included. From 7470 articles identified by the initial search strategy, nine
      studies with a total of 476 legs were included in this review. All studies were
      cadaveric and subjects ranged from stillborn fetuses to 103 years of age. Studies
      suggested that femoral veins contain between one and six valves, and popliteal
      veins contain between zero and four valves. Deep vein valves were consistently
      located in the common femoral vein (within 5 cm of the inguinal ligament), the
      femoral vein (within 3 cm of the deep femoral vein tributary) and in the
      popliteal vein near the adductor hiatus. Valves are consistently located at
      specific locations in the deep veins of the leg, although there is often
      significant variability between subjects. Further anatomical and functional
      studies using new imaging modalities available should target these areas to
      identify whether certain valves play a more important role in venous disease.
      This may guide us in the development of new treatment options for patients with
      deep venous disease.

PMID- 21740425
TI  - Glucose transporters GLUT4 and GLUT8 are upregulated after facial nerve axotomy
      in adult mice.
AB  - Peripheral nerve axotomy in adult mice elicits a complex response that includes
      increased glucose uptake in regenerating nerve cells. This work analyses the
      expression of the neuronal glucose transporters GLUT3, GLUT4 and GLUT8 in the
      facial nucleus of adult mice during the first days after facial nerve axotomy.
      Our results show that whereas GLUT3 levels do not vary, GLUT4 and GLUT8
      immunoreactivity increases in the cell body of the injured motoneurons after the
      lesion. A sharp increase in GLUT4 immunoreactivity was detected 3 days after the
      nerve injury and levels remained high on Day 8, but to a lesser extent. GLUT8
      also increased the levels but later than GLUT4, as they only rose on Day 8 post
      lesion. These results indicate that glucose transport is activated in
      regenerating motoneurons and that GLUT4 plays a main role in this function. These
      results also suggest that metabolic defects involving impairment of glucose
      transporters may be principal components of the neurotoxic mechanisms leading to
      motoneuron death.

PMID- 21740426
TI  - Spatially-dense 3D facial asymmetry assessment in both typical and disordered
      growth.
AB  - Mild facial asymmetries are common in typical growth patterns. Therefore,
      detection of disordered facial growth patterns in individuals characterized by
      asymmetries is preferably accomplished by reference to the typical variation
      found in the general population rather than to some ideal of perfect symmetry,
      which rarely exists. This presents a challenge in developing an asymmetry
      assessment tool that is applicable, without modification, to detect both mild and
      severe facial asymmetries. In this paper we use concepts from geometric
      morphometrics to obtain robust and spatially-dense asymmetry assessments using a
      superimposition protocol for comparison of a face with its mirror image.
      Spatially-dense localization of asymmetries was achieved using an anthropometric
      mask consisting of uniformly sampled quasi-landmarks that were automatically
      indicated on 3D facial images. Robustness, in the sense of an unbiased analysis
      under increasing asymmetry, was ensured by an adaptive, robust, least-squares
      superimposition. The degree of overall asymmetry in an individual was scored
      using a root-mean-squared-error, and the proportion was scored using a novel
      relative significant asymmetry percentage. This protocol was applied to a
      database of 3D facial images from 359 young healthy individuals and three
      individuals with disordered facial growth. Typical asymmetry statistics were
      derived and were mainly located on, but not limited to, the lower two-thirds of
      the face in males and females. The asymmetry in males was more extensive and of a
      greater magnitude than in females. This protocol and proposed scoring of
      asymmetry with accompanying reference statistics will be useful for the detection
      and quantification of facial asymmetry in future studies.

PMID- 21740427
TI  - Development and evaluation of the school cafeteria nutrition assessment measures.
AB  - BACKGROUND: Foods provided in schools represent a substantial portion of US
      children's dietary intake; however, the school food environment has proven
      difficult to describe due to the lack of comprehensive, standardized, and
      validated measures. METHODS: As part of the Arkansas Act 1220 evaluation project,
      we developed the School Cafeteria Nutrition Assessment (SCNA) measures to assess
      food availability in public school cafeterias (n = 113). The SCNA provides a
      measure to evaluate monthly school lunch menus and to observe foods offered in
      school cafeterias during the lunch period. These measures provide information on
      the availability of fruit, vegetables, grains (whole or white), chips (reduced
      fat or regular), side dishes, main dishes, beverages, a la carte selections, and
      desserts, as well as information on healthier preparation of these items. Using
      independent raters, the inter-rater reliability of the measure was determined
      among a subsample of these schools (n = 32). RESULTS: All food categories
      assessed, with the exception of the side dish and chip categories, had inter
      rater reliability rates of 0.79 or greater, regardless of school type. The SCNA
      scores encompassed the majority of the possible scores, indicating the ability
      for the measures to differentiate between school cafeterias in the availability
      of healthier options. CONCLUSION: These measures allow comprehensive, rapid
      measurement of school cafeteria food availability with high inter-rater
      reliability for public health and school health professionals, communities, and
      school personnel. These measures have the potential to contribute to school
      health efforts to evaluate cafeteria offerings and/or the impact of policy
      changes regarding school foods.

PMID- 21740428
TI  - Regional differences as barriers to body mass index screening described by Ohio
      school nurses.
AB  - BACKGROUND: Body mass index (BMI) screening is advocated by the National
      Association of School Nurses (NASN). Research identifying barriers to BMI
      screening in public elementary school settings has been sparse. The purpose of
      the study was to identify barriers and facilitating factors of BMI screening
      practices among Ohio school nurses working in suburban, rural, and urban public
      elementary schools. METHODS: This descriptive study used focus groups with 25
      school nurses in 3 geographic regions of Ohio. An adapted Healthy People 2010
      model guided the development of semistructured focus group questions. RESULTS:
      Nine regional themes related to BMI screening emerged specific to suburban,
      rural, and/or urban school nurses' experiences with BMI screening practice,
      policy, school physical environment, school social environment, school
      risk/protection, and access to quality health care. Key facilitating factors to
      BMI screening varied by region. Key barriers to BMI screening were a lack of
      privacy, time, policy, and workload of school nurses. CONCLUSION: Regionally
      specific facilitating factors to BMI screening in schools provide opportunities
      for schools to accentuate the positive and to promote school health.

PMID- 21740429
TI  - School sports opportunities influence physical activity in secondary school and
      beyond.
AB  - BACKGROUND: The purpose of the present study was to examine whether the
      availability of intramural or extramural sports in secondary schools is
      associated with physical activity levels in youth throughout secondary school and
      at age 20. METHODS: Eight hundred and eight adolescents from 10 secondary schools
      in Montreal, Canada, provided physical activity data every 3 months during the
      school year from ages 13 to 17, and again at age 20. School administrators
      completed questionnaires on the availability of intramural and extramural sports.
      Three-level general linear models were used to examine associations among the
      number of intramural and extramural sports, moderate and vigorous physical
      activity controlling for age, sex, body mass index, mother's education, and
      school-level socioeconomic status. RESULTS: Regardless of whether or not they
      reported participating in intramural sports, adolescents in schools with more
      intramural sports engaged in 3.6 (p = .03) more total, and 1.3 (p = 0.03) more
      vigorous activities per week than those attending schools with fewer intramural
      sports. Number of extramural sports was not statistically significantly
      associated with physical activity, regardless of whether or not individual
      students participated. CONCLUSION: Providing more opportunities for intramural
      sports in secondary schools may be an effective strategy to help adolescents
      attain physical activity recommendations.

PMID- 21740430
TI  - Effect of a low-cost, teacher-directed classroom intervention on elementary
      students' physical activity.
AB  - BACKGROUND: Effective physical activity (PA) interventions are warranted for
      youth, and schools have been identified as logical locations for such
      involvement. Experts and professionals in the field promote comprehensive school
      PA programs, including classroom PA. The purpose of this study was to determine
      the effect of a low-cost, teacher-directed classroom-based intervention on the
      school PA of elementary children. METHODS: Nine classroom teachers were provided
      inexpensive curricula and trained to implement and instruct PA breaks (2 * 30
      minute training sessions). The teachers were encouraged to lead 1 activity break
      per day after the training. One hundred and six elementary students wore
      pedometers up to 12 days over 3 monitoring periods during the school year
      (baseline, follow-up, post follow-up) to assess the effectiveness and the
      sustainability of the intervention. The teachers self-reported the frequency of
      activity breaks instructed. RESULTS: The teachers (n = 5) who complied with the
      recommended 1 activity break per day had students who accrued ~33% more mean
      school steps/day at follow-up (~1100) and post follow-up (~1350) compared to
      controls. Teachers (n = 4) in the intervention who did not comply with the 1
      activity break per day recommendation had students accrue similar mean school
      steps/day as controls. CONCLUSION: Inexpensive, teacher-directed classroom-based
      PA interventions can be effective in improving children's PA levels if teachers
      implement 1 activity break per school day. We recommend promoting the notion of 1
      activity break per day in the classroom as part of a comprehensive school PA
      program that includes quality physical education, recess, and before/after school
      programs.

PMID- 21740431
TI  - Physical activity and positive youth development: impact of a school-based
      program.
AB  - BACKGROUND: Protective factors associated with positive youth development predict
      health and education outcomes. This study explored trends in these protective
      factors and in physical activity among low-income students, and determined the
      impact of a school-based youth development program on these trends. METHODS: This
      study used a quasi-experimental time series design including data from 158 low
      income schools from 2001 to 2007. Ninety-four schools had exposure to a school
      based program promoting physical activity and youth development through
      structured play; 64 schools served as controls. Primary outcomes were 5th-grade
      student scores (n = 13,109) on a California statewide survey for physical
      activity (1-6 scale) and measures of protective factors including problem solving
      skills, meaningful participation in school, and caring adults (1-4 scales).
      Predictors were time (year) and school's number of years of exposure to the
      program. RESULTS: Overall, significant annual declines were seen in protective
      factors, including students' report of feeling safe (-0.03, 95% CI [-0.03, 
      0.01]), caring adults at school (-0.03 [-0.05, -0.02]), and problem solving
      skills (-0.03 [-0.04, -0.02]). Cumulative declines over 6 years were equivalent
      to a drop of 1 school-level SD. Each additional year of exposure to the program
      predicted greater meaningful participation (0.02 [0.001, 0.5]), problem-solving
      skills (0.03 [0.0001, 0.06]), and increased physical activity (0.06 [0.01,
      0.10]); exposure throughout elementary school (6 years) increased scores by 1
      school-level SD. CONCLUSIONS: Low-income students reported a significant decline
      in protective factors since 2001. School partnerships with youth development
      programs promoting physical activity may ameliorate declines in emotional well
      being and increase physical activity.

PMID- 21740432
TI  - Preparedness for students and staff with anaphylaxis.
AB  - BACKGROUND: Schools are responsible for handling life-threatening events due to a
      variety of conditions, including anaphylaxis. California is one of a few states
      that permits school districts to stock emergency epinephrine auto-injectors and
      to train unlicensed assistive personnel to administer epinephrine for a life
      threatening event. We surveyed school nurses in California to explore their
      experience with life-threatening anaphylaxis, implementation of allowable stock
      epinephrine auto-injector programs, and the barriers to program implementation.
      METHODS: An exploratory, cross-sectional, descriptive design was used for this
      study. Data was obtained from a convenience sample of 171 credentialed California
      school nurses via an online survey service. Descriptive statistics and Pearson's
      chi-square were used to analyze the data. RESULTS: Thirty percent of school
      nurses reported using 1 student's prescribed medication to rescue another student
      in distress. Despite the frequency of using another student's rescue medication
      and California's permissive policy, only 13% of nurses reported having stock
      epinephrine programs. Barriers to stock epinephrine programs included: (a)
      limited availability of school nursing services, (b) lack of policies or
      guidelines, (c) inadequate funding for training and medication, and (d) lack of
      education. Limited awareness of susceptibility and the immediate life-threatening
      nature of anaphylaxis were also contributing factors. CONCLUSIONS: Legislative
      initiatives are sufficient to develop safe, effective policies and protocols to
      manage life-threatening allergic reaction in schools. The findings indicate that
      more education is needed for school personnel and research is needed to determine
      an effective mechanism to remove barriers for emergency care during school hours.

PMID- 21740433
TI  - Cultural tailoring and feasibility assessment of a sexual health middle school
      curriculum: a pilot test in Puerto Rico.
AB  - BACKGROUND: To assess the need for cultural tailoring of an effective sexual
      health middle school curriculum, "It's Your Game: Keep It Real" (IYG), prior to
      implementation in Puerto Rican (PR) middle schools. METHODS: Seventy-three
      seventh-grade bilingual students participated in IYG curriculum activities (both
      group-based and computer-based) in two 2-hour testing sessions in spring 2008.
      Rating scales of acceptability, understandability, credibility, ease of use, and
      motivational appeal and qualitative feedback via open-ended responses and group
      process provided insight into needed surface and deep structure cultural
      tailoring. RESULTS: Students rated IYG highly on cultural tailoring and
      motivational parameters and were highly engaged by the lesson content. School
      personnel rated IYG as a feasible strategy for use in PR middle schools. While
      surface cultural elements (eg, characters, attire, body language) were identified
      as important foci for adaptation, content related to deeper cultural elements
      such as core behaviors, risky situations, attitudes, and specific skills were
      considered as relevant to PR youth as to their US counterparts. CONCLUSION:
      Effective human immunodeficiency virus, sexually transmitted disease, and
      pregnancy skills training prevention programs such as IYG that are developed for
      minority US youth may offer a feasible option for international implementation
      when extensive cultural adaptation is not a viable option.

PMID- 21740434
TI  - The impact of truant and alcohol-related behavior on educational aspirations: a
      study of US high school seniors.
AB  - BACKGROUND: Truancy and alcohol use are quality indicators of academic
      achievement and success. However, there remains a paucity of substantive research
      articulating the impact these deviant behaviors have on an adolescent's
      educational aspirations. The purpose of this study is to assess whether recent
      alcohol use and truancy impact students' educational aspirations among a
      nationally representative sample of US high school seniors. METHODS: This study
      conducted a secondary data analysis of the Monitoring the Future project data,
      2006. Logistic regression was conducted to assess how alcohol use and truancy
      affected educational aspirations. Subsequent interaction effects were assessed in
      the final multivariable model. Demographic variables such as age, sex, race, and
      father and mother's educational level were included as covariates in the
      regression model. RESULTS: Results indicate that as students engage in increased
      alcohol use and/or truancy, educational aspirations decrease. Thus, students who
      indicated a desire to attend a 4-year college/university were less likely to
      engage in high-risk drinking behavior and/or truancy. Moreover, in testing the
      interaction between truancy and alcohol use, as it relates to educational
      aspirations, the logistic regression model found both of these independent
      variables to be statistically significant predictors of the likelihood students
      would attend a 4-year college/university. CONCLUSIONS: To ensure that adolescents
      further their education and maximize their potential life opportunities, school
      and public health officials should initiate efforts to reduce alcohol consumption
      and truancy among students. Furthermore, future research should examine the risk
      and protective factors that may influence one's educational aspirations.

PMID- 21740435
TI  - Meeting the social and behavioral health needs of students: rethinking the
      relationship between teachers and school social workers.
AB  - BACKGROUND: While school-based mental health professionals obviously must provide
      mental health services to students directly, the literature is increasingly
      identifying an empowerment role for these professionals, whereby they support
      teachers as primary service providers. The purpose of this study was to identify
      subtypes of school social workers within the context of collaborative practice,
      and to identify individual and contextual factors associated with these
      classifications as well as overall levels of collaboration. METHODS: Latent class
      analysis, conducted using data collected as part of the National School Social
      Work Survey 2008 (N = 1639), was employed to examine underlying subtypes of
      school social work practitioners in relation to collaborative practices and to
      examine predictors of collaborative practice. RESULTS: Four broad categories of
      school social workers were identified, including (1) noncollaborators, (2) system
      level specialists, (3) consultants, and (4) well-balanced collaborators. These
      classes were associated with the number of schools served, grade level,
      education, and clinical licensure status; level of administrative responsibility
      was not associated with class membership. CONCLUSION: While school social workers
      varied in collaborative practices, opportunities exist to enhance their role in
      educating and supporting teachers to serve as primary providers to students with
      social, mental health, and behavioral needs. The implications for school-based
      mental health providers, teachers, administrators, policymakers, and researchers
      are discussed.

PMID- 21740436
TI  - Results of evaluability assessments of local wellness policies in 6 US school
      districts.
AB  - BACKGROUND: A US federal mandate that school districts devise and implement local
      wellness policies (LWPs) has potential widespread impact on the nutritional
      content of foods and beverages available in schools and on the amount of physical
      activity that students engage in; however, evidence concerning the mandate's
      effectiveness is limited. This study describes the content of LWPs of 6 US school
      districts and steps taken toward their implementation and evaluation. METHODS:
      During visits to 6 school districts, we interviewed 88 school and community
      representatives about the content of their district's LWPs and how the LWPs were
      being implemented and evaluated. RESULTS: The 6 LWPs were consistent with the
      federal mandate, although they varied in content and degree of specificity, and
      none had been fully implemented. All 6 districts were pursuing strategies to
      ensure that foods and beverages available at school met nutrition standards but
      did not offer nutrition education to all K-12 students. All 6 districts offered
      students only limited opportunities for physical activity, and all 6 collected
      data to monitor process and outcomes of their LWPs. CONCLUSIONS: Partial
      implementation of LWPs in the districts we visited resulted in significant
      improvement in the nutritional quality of foods available at district schools,
      but only slight improvement in students' opportunities for school-based physical
      activity. We provide recommendations for school districts on implementation and
      evaluation. Future research is needed to determine the impact of these LWPs on
      students' health.

PMID- 21740437
TI  - Hyperostosis frontalis interna (HFI) and castration: the case of the famous
      singer Farinelli (1705-1782).
AB  - The famous castrato singer Farinelli (1705-1782) was exhumed by our research
      group in July 2006 for the purpose of gaining some insight into his biological
      profile through a study of his skeletal remains. Farinelli was castrated before
      puberty to preserve the treble pitch of the boy's voice into adult life. His
      powerful and sweet voice became legendary. In spite of its bad preservation
      state, the skeleton displayed some interesting characteristics that are probably
      related to the effects of castration, including long limb-bones, persistence of
      epiphyseal lines and osteoporosis. In particular, the frontal bone was affected
      by severe hyperostosis frontalis interna (HFI). This condition consists in a
      symmetrical thickening of the inner table of the bone. The epidemiology of HFI
      shows that it is relatively common in postmenopausal women but very rare in men.
      Men affected by this pathology suffer from diseases, syndromes or treatments
      causing androgen deficiency. In the case of Farinelli, castration was probably
      responsible for the onset and development of this lesion.

PMID- 21740438
TI  - Amantadine attenuates levodopa-induced dyskinesia in mice and rats preventing the
      accompanying rise in nigral GABA levels.
AB  - Amantadine is the only drug marketed for treating levodopa-induced dyskinesia.
      However, its impact on basal ganglia circuitry in the dyskinetic brain,
      particularly on the activity of striatofugal pathways, has not been evaluated. We
      therefore used dual probe microdialysis to investigate the effect of amantadine
      on behavioral and neurochemical changes in the globus pallidus and substantia
      nigra reticulata of 6-hydroxydopamine hemi-lesioned dyskinetic mice and rats.
      Levodopa evoked abnormal involuntary movements (AIMs) in dyskinetic mice, and
      simultaneously elevated GABA release in substantia nigra reticulata (~3-fold) but
      not globus pallidus. Glutamate levels were unaffected in both areas. Amantadine
      (40 mg/kg, i.p.), ineffective alone, attenuated (~50%) AIMs expression and
      prevented the GABA rise. Moreover, it unraveled a facilitatory effect of levodopa
      on pallidal glutamate levels. Levodopa also evoked AIMs expression and a GABA
      surge (~2-fold) selectively in the substantia nigra of dyskinetic rats. However,
      different from mice, glutamate levels rose simultaneously. Amantadine,
      ineffective alone, attenuated (~50%) AIMs expression preventing amino acid
      increase and leaving unaffected pallidal glutamate. Overall, the data provide
      neurochemical evidence that levodopa-induced dyskinesia is accompanied by
      activation of the striato-nigral pathway in both mice and rats, and that the anti
      dyskinetic effect of amantadine partly relies on the modulation of this pathway.

PMID- 21740440
TI  - Intracellular distribution of functional M(1) -muscarinic acetylcholine receptors
      in N1E-115 neuroblastoma cells.
AB  - Signaling by muscarinic agonists is thought to result from the activation of cell
      surface acetylcholine receptors (mAChRs) that transmit extracellular signals to
      intracellular systems. In N1E-115 neuroblastoma cells, we detected both plasma
      membrane and intracellular M(1) -mAChRs using both biochemical and
      pharmacological methods. In intact cells, both plasma membrane and intracellular
      M(1) -mAChRs were detected by the hydrophobic ligand probe, 1-quinuclidinyl
      [phenyl-4-(3) H]-benzilate ([(3) H]-QNB) whereas the hydrophilic probe, 1-[N
      methyl-(3) H] scopolamine ([(3) H]-NMS), detected only cell surface receptors.
      These probes detected comparable numbers of receptors in isolated membrane
      preparations. Immunohistochemical studies with M(1) -mAChR antibody also detected
      both cell-surface and intracellular M(1) -mAChRs. Carbachol-stimulated
      phosphatidylinositol hydrolysis and Ca(2+) mobilization were completely inhibited
      by a cell-impermeable M(1) antagonist, muscarinic toxin -7 and the G(q/11)
      inhibitor YM-254890. However, carbachol-stimulated extracellular-regulated kinase
      1/2 activation was unaffected by muscarinic toxin-7, but was blocked by the cell
      permeable antagonist, pirenzepine. extracellular regulated kinase 1/2
      phosphorylation was resistant to blockade of G(q/11) (YM-254890) and protein
      kinase C (bisindolylmaleimide I). Our data suggest that the geographically
      distinct M(1) -mAChRs (cell surface versus intracellular) can signal via unique
      signaling pathways that are differentially sensitive to cell-impermeable versus
      cell-permeable antagonists. Our data are of potential physiological relevance to
      signaling that affects both cognitive and neurodegenerative processes.

PMID- 21740439
TI  - Tumor necrosis factor-alpha synthesis inhibitor, 3,6'-dithiothalidomide, reverses
      behavioral impairments induced by minimal traumatic brain injury in mice.
AB  - Mild traumatic brain injury (mTBI) patients do not show clear structural brain
      defects and, in general, do not require hospitalization, but frequently suffer
      from long-lasting cognitive, behavioral and emotional difficulties. Although
      there is no current effective treatment or cure for mTBI, tumor necrosis factor
      alpha (TNF-alpha), a cytokine fundamental in the systemic inflammatory process,
      represents a potential drug target. TNF-alpha levels increase after mTBI and may
      induce or exacerbate secondary damage to brain tissue. The present study
      evaluated the efficacy of the experimental TNF-alpha synthesis inhibitor, 3,6'
      dithiothalidomide, on recovery of mice from mTBI in a closed head weight-drop
      model that induces an acute elevation in brain TNF-alpha and an impairment in
      cognitive performance, as assessed by the Y-maze, by novel object recognition and
      by passive avoidance paradigms at 72 h and 7 days after injury. These impairments
      were fully ameliorated in mice that received a one time administration of 3,6'
      dithiothalidomide at either a low (28 mg/kg) or high (56 mg/kg) dose provided
      either 1 h prior to injury, or at 1 or 12 h post-injury. Together, these results
      implicate TNF-alpha as a drug target for mTBI and suggests that 3,6'
      dithiothalidomide may act as a neuroprotective drug to minimize impairment.

PMID- 21740441
TI  - N-acetylaspartylglutamate is an agonist at mGluR3 in vivo and in vitro.

PMID- 21740443
TI  - Mutants of beta-strand beta3 and the loop B in the interface between alpha7
      subunits of a homomeric acetylcholine receptor show functional and
      pharmacological alterations.
AB  - Activation of nicotinic acetylcholine receptors (nAChR) requires a global
      conformational change involving a number of domains of the protein. Structural
      data from Torpedo nAChR suggest that adjacent subunits might be functionally
      coupled at the interface between the beta-strand beta3 and the loop B through a
      salt bridge between alpha1Asp152 and gammaArg78. We have checked this hypothesis
      in homomeric alpha7 nAChRs by mutating residues at these (Gly152 and Arg79) and
      neighboring locations and analyzing the results obtained after expression of
      single and double mutants in Xenopus oocytes. We found that Arg79 mutants showed
      a decreased gating function when challenged with different agonists, being the
      reduction more important for dimethylphenylpiperazinium. EC(50) values in these
      mutants were also increased up to 30-fold. In contrast, mutating Gly152 only
      showed significant higher EC(50) values for ACh. However, all Gly153 mutants
      presented increased gating function and lower EC(50) values with no significant
      differences among them. When analyzing several mutant cycles it is concluded that
      Arg79 is functionally coupled to Gly152, but neither to Gly153 nor to Asp157.
      These data suggest an involvement of the minus side of homomeric alpha7 nAChRs in
      their gating function, reinforcing the significance of complementary subunits in
      the gating of neuronal nAChRs.

PMID- 21740442
TI  - Neuronal tryptophan hydroxylase expression in BALB/cJ and C57Bl/6J mice.
AB  - BALB/c is an inbred stress-sensitive mouse strain exhibiting low brain serotonin
      (5-HT) content and a 5-HT biosynthetic enzyme tryptophan hydroxylase (Tph2)
      variant reported to have lower catalytic activity compared with other inbred base
      strains. To evaluate other mechanisms that may explain low 5-HT, we compared
      BALB/cJ mice and a control inbred strain C57Bl/6J mice, for expression of Tph2
      mRNA, TPH2 protein and regional levels of 5-HT and its metabolite 5
      hydroxyindoleacetic acid. Tph2 mRNA and TPH2 protein in brainstem dorsal raphe
      nuclei was assayed by in situ hybridization and immunocytochemistry respectively.
      5-HT and 5-hydroxyindoleacetic acid were determined by HPLC. BALB/cJ mice had 20%
      less Tph2 mRNA and 28% fewer TPH2 immunolabeled neurons than C57Bl/6J mice (t = 
      2.59, p = 0.02). The largest difference in Tph2 transcript expression was in
      rostral dorsal raphe nuclei (t = 2.731, p = 0.008). 5-HT was 15% lower in the
      midbrain and 18% lower in the cerebral cortex of BALB/cJ compared with C57Bl/6J
      mice (p < 0.05). The behavioral differences in BALB/cJ mice relative to the
      C57Bl/6J strain may be due in part, to fewer 5-HT neurons and lower Tph2 gene
      expression resulting in less 5-HT neurotransmission. Future studies quantifying
      expression per neuron are needed to determine whether less expression is
      explained by fewer neurons or also less expression per neuron, or both.

PMID- 21740444
TI  - Artificial photosynthesis: from molecular catalysts for light-driven water
      splitting to photoelectrochemical cells.
AB  - Photosynthesis has been for many years a fascinating source of inspiration for
      the development of model systems able to achieve efficient light-to-chemical
      energetic transduction. This field of research, called "artificial
      photosynthesis," is currently the subject of intense interest, driven by the aim
      of converting solar energy into the carbon-free fuel hydrogen through the light
      driven water splitting. In this review, we highlight the recent achievements on
      light-driven water oxidation and hydrogen production by molecular catalysts and
      we shed light on the perspectives in terms of implementation into water splitting
      technological devices.

PMID- 21740445
TI  - Effect of gamma irradiation and restorative material on the biomechanical
      behaviour of root filled premolars.
AB  - AIM: To investigate ex vivo the influence of gamma irradiation therapy and
      restorative material on fracture resistance, fracture mode and strain of root
      filled human premolars. METHODOLOGY: Sixty extracted human maxillary premolar
      teeth were randomly divided into six groups (n = 10) determined by two study
      factors: (i) restorative materials: sound teeth, root filled teeth restored with
      composite resin, root filled teeth restored with amalgam; (ii) gamma irradiation:
      irradiated (subjected to 60 Gy of gamma irradiation in daily increments of 2 Gy)
      and nonirradiated. For the strain gauge test, two strain gauges per sample were
      attached on the buccal and palatal cusp surfaces (n = 5). Strain values were
      recorded during loading of 0-150 N. Fracture resistance (N) was assessed in a
      mechanical testing machine (n = 10). Strain gauge for each cusp and fracture
      resistance data were analysed by two-way anova (3 * 2) followed by the Tukey's
      honestly significant difference test (alpha = 0.05). The failure mode was
      evaluated using an optical stereomicroscope and classified according to the
      location of the failure. RESULTS: Gamma radiation therapy significantly reduced
      the fracture resistance of intact teeth. The strain was higher for teeth restored
      with amalgam than for those restored with composite resin. The teeth restored
      with composite resin had similar strain values to sound teeth. Nonirradiated
      teeth had more restorable failures than irradiated teeth. CONCLUSIONS: Gamma
      irradiation significantly reduced fracture resistance and increased cusp strain.
      The use of composite resin resulted in better biomechanical behaviour than
      amalgam for restoring root filled teeth whether or not they were submitted to
      radiotherapy.

PMID- 21740446
TI  - Detection of Tobacco mosaic virus and Tomato mosaic virus in pepper and tomato by
      multiplex RT-PCR.
AB  - AIMS: To develop a highly sensitive and rapid protocol for simultaneous detection
      and differentiation of Tobacco mosaic virus (TMV) and Tomato mosaic virus (ToMV)
      in pepper and tomato. In this study, we use the multiplex PCR technique to detect
      dual infection of these two viruses. METHODS AND RESULTS: A multiplex RT-PCR
      method consisting of one-tube reaction with two primer pairs targeted to
      replicase genes was developed to simultaneously detect TMV and ToMV in seed
      samples of pepper and tomato. Specific primers were designed from conserved
      regions of each of the virus genomes, and their specificity was confirmed by
      sequencing PCR products. RT-PCR detected up to 10(-6) dilution of total RNA
      extracted from infected leaves. Multiplex RT-PCR revealed the presence of both
      TMV and ToMV in three of 18 seed samples of tomato and one of 18 seed samples of
      pepper. CONCLUSIONS: The multiplex PCR assay was a cost effective, quick
      diagnostic technique, which was helpful in differentiating TMV and ToMV
      accurately. SIGNIFICANCE AND IMPACT OF THE STUDY: The multiplex PCR assay
      described in this study is a valuable tool for plant pathology and basic research
      studies. This method may facilitate better recognition and distinction of TMV and
      ToMV in both pepper and tomato.

PMID- 21740447
TI  - Behaviour of Listeria monocytogenes in packaged water buffalo mozzarella cheese.
AB  - AIMS: The aim of the study was to evaluate the behaviour of Listeria
      monocytogenes in the conditioning liquid of packaged water buffalo mozzarella
      cheese (WBMC). METHODS AND RESULTS: The conditioning liquid was contaminated with
      L. monocytogenes, and the contaminated samples were stored at four different
      storage temperatures: 5 and 10  degrees C for 22 days; 20  degrees C for 9 days;
      20  degrees C for 3 days and then at 5  degrees C for 6 days. The results showed
      that L. monocytogenes concentration decreased when contaminated samples were
      stored at 5  degrees C. When WBMC was stored at 20  degrees C and at 10  degrees
      C, L. monocytogenes started to grow after a lag phase of 3 and 10 days,
      respectively. When samples were stored at variable temperature conditions, L.
      monocytogenes numbers showed a lag phase of 5 days. CONCLUSIONS: Use of a
      conditioning liquid characterized by acidity and a correct storage temperature is
      able to counteract pathogen replication during shelf life. A high concentration
      of lactic acid bacteria was associated with effective control of L. monocytogenes
      but the role of lactic acid bacteria in WBMC conditioning liquid requires further
      investigation. SIGNIFICANCE AND IMPACT OF THE STUDY: According to European
      regulations, food producers should be able to justify decision-making on the
      shelf life assigned to their products, taking into account reasonable storage
      conditions and use by consumers. The results of the trial yielded information for
      producers of WBMC and similar cheeses for decision-making on product shelf life.

PMID- 21740448
TI  - Vibrio virulence genes in fishes collected from estuarine waters in Italy.
AB  - AIMS: The aim of this study was to investigate the presence of Vibrio vulnificus
      and potentially pathogenic strains of Vibrio parahaemolyticus in mullets
      collected from estuarine environment in Italy. METHODS AND RESULTS: Two hundred
      and ninety-five mullets were analysed by culture using the selective medium
      thiosulfate citrate bile salt sucrose agar, during a monitoring period of 2 years
      (2008-2009). Presumptive Vibrio colonies were initially identified by using
      biochemical tests, and strains identified as V. parahaemolyticus and V.
      vulnificus were subsequently examined by PCR for the presence of species-specific
      and virulence genes (toxR, trh, tdh and vvh). V. parahaemolyticus was found in
      55% (162/295) of fishes and V. vulnificus in 1% (3/295) with a higher presence in
      summer months. The trh+/tdh- strains were detected in 16% (47/295) of samples and
      only one strain resulted trh+/tdh+. One of the V. parahaemolyticus trh+ strains
      isolated belonged to the O1:KUT (K untypeable), a serotype recently associated to
      gastroenteritis in Italy. CONCLUSIONS: This is the first report demonstrating a
      high percentage of potential pathogenic V. parahaemolyticus trh+ strains in
      estuarine fishes of the Mediterranean area. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These findings indicate the potential human health risk associated with the
      presence of pathogenic Vibrio spp. in wild fishes.

PMID- 21740449
TI  - Expression of Lactobacillus brevis IOEB 9809 tyrosine decarboxylase and agmatine
      deiminase genes in wine correlates with substrate availability.
AB  - AIMS: Lactobacillus brevis IOEB 9809 is able to produce both tyramine and
      putrescine via tyrosine decarboxylase and agmatine deiminase enzymes,
      respectively, when cultured on synthetic media. The aims of this study were to
      assess the expression of L. brevis IOEB 9809 tdc and aguA1 genes, during wine
      fermentation and to evaluate the effect of substrate availability and pH on tdc
      and aguA1 expression, as well as on biogenic amine production and L. brevis
      viability. METHODS AND RESULTS: The relative expression of L. brevis IOEB 9809
      tdc and aguA1 genes was analysed in wine by quantitative real-time RT-PCR (qRT
      PCR) during a period of incubation of 30 days. Cell viability, pH values,
      putrescine and tyramine concentration were monitored throughout the experiments.
      CONCLUSIONS: The wine trials indicated that L. brevis IOEB 9809 is able to
      produce both tyramine and putrescine during wine fermentation. Increased cell
      viability was also observed in wine supplemented with tyrosine or agmatine. qRT
      PCR analysis suggests a strong influence of substrate availability on the
      expression of genes coding for tyrosine decarboxylase and agmatine deiminase in
      L. brevis IOEB 9809. Less evident is the relationship between putrescine and
      tyramine production and tolerance to wine pH. SIGNIFICANCE AND IMPACT OF STUDY:
      To our knowledge, this study represents the first assessment of relative
      expression of L. brevis IOEB 9809 genes involved in biogenic amine production in
      wine. Furthermore, an effect of biogenic amine production on viability of L.
      brevis during wine fermentation was established.

PMID- 21740450
TI  - CB1-independent mechanisms of Delta9-THCV, AM251 and SR141716 (rimonabant).
AB  - WHAT IS KNOWN AND OBJECTIVE: The potential beneficial therapeutic effects of
      cannabinoid CB1 receptor antagonists or partial agonists have driven drug
      discovery and development efforts and have led to clinical candidates. It is
      generally assumed that these compounds are CB1 'selective' and produce their
      effects exclusively via CB1 receptors. METHODS: A literature search was conducted
      of preclinical publications containing information about non-CB1 receptor
      pharmacology of these agents. The information was summarized and evaluated from
      the perspective of contribution to a fuller understanding of this aspect of these
      compounds. RESULTS AND DISCUSSION: A number of recent studies have revealed that
      these compounds have CB1-independent pharmacological actions. We highlight the
      evidence regarding effects produced in cells lacking CB1 receptors, effects on
      neuronal membranes from CB1 receptor-deficient mutant KO 'knockout' mice and
      affinity for MU-opioid receptors. WHAT IS NEW AND CONCLUSION: CB1 'selective'
      antagonists and partial agonists have been studied for their anorexigenic and
      other potential therapeutic uses. An awareness of CB1-independent mechanism(s) of
      these agents might contribute to a better understanding of the pharmacologic and
      toxicologic profiles of these agents.

PMID- 21740451
TI  - Effect of long-acting beta-agonists on the frequency of COPD exacerbations: a
      meta-analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE:   Inhaled long-acting beta-agonists have been
      licensed for the treatment of chronic obstructive pulmonary disease (COPD) since
      the late 1990s, and they improve lung function and symptoms of dyspnoea. However,
      the evidence that long-acting beta-agonists alone can reduce the rate of COPD
      exacerbations is not conclusive. This meta-analysis was performed to evaluate
      their effect on the frequency of exacerbations. METHODS: MEDLINE, EMBASE, CINAHL
      and the Cochrane trials database were searched for the review. Randomized
      controlled trials of greater than or equal to 24weeks' treatment duration
      comparing long-acting beta-agonists (LABAs) with placebo were reviewed. Studies
      were pooled to yield odds ratios (ORs) with 95% confidence intervals (CIs).
      RESULTS AND DISCUSSION: Seventeen randomized controlled trials (11871 randomized
      subjects) met the inclusion criteria and were selected for analysis. Salmeterol,
      formoterol and indacaterol significantly reduced COPD exacerbations compared with
      placebo. Salmeterol significantly reduced COPD exacerbations with both study arms
      exposed or not exposed to inhaled corticosteroids (ICS). The summary ORs were
      0.79 (95% CI: 0.67-0.92; P<0.01) and 0.80 (95% CI: 0.65-0.99; P=0.04),
      respectively. However, when both arms were not exposed to ICS, there was no
      significant reduction in exacerbations with formoterol compared with placebo. The
      'summary OR was 0.93 (95% CI: 0.75-1.15; P=0.50). WHAT IS NEW AND CONCLUSION:
      Long-acting beta-agonists reduce the frequency of COPD exacerbations. Salmeterol,
      formoterol and indacaterol significantly reduced COPD exacerbations compared with
      placebo. Salmeterol but not formoterol decreased exacerbations significantly in
      the absence of ICS.

PMID- 21740452
TI  - Supplementing vitamins C and E to standard triple therapy for the eradication of
      Helicobacter pylori.
AB  - WHAT IS KNOWN AND OBJECTIVE: Helicobacter pylori eradication rates of currently
      accepted triple therapy regimens vary between geographic locations and do not
      exceed 70-80%. Eradication rates are much lower in locations where uncontrolled
      antibiotic use is common such as Turkey. In the present study, we aimed to test
      whether supplementing vitamins C and E to standard triple therapy, including a
      proton pump inhibitor plus amoxicillin plus clarithromycin, increased the H.
      pylori eradication rate. METHODS: Two hundred patients infected with H. pylori
      were randomized into two groups in an open-label trial. In group A, patients (n =
      160) were given standard triple therapy, including lansoprazole 30 mg BID plus
      amoxicillin 1000 mg BID plus clarithromycin 500 mg BID for 14 days, plus vitamin
      C 500 mg BID plus vitamin E 200 IU BID for 30 days. In group B, patients (n = 40)
      were given standard triple therapy for 14 days. The success of H. pylori
      eradication was defined as a negative 14C-urea breath test result, 4-6 weeks
      after the completion of therapy. Comaprisons were by both intention-to-treat
      (ITT) and per-protocol (PP) analysis. RESULTS AND DISCUSSION: Two hundred
      patients (137 women, 63 men) were analysed using ITT analysis and 195 patients
      completed the study. In group A, H. pylori eradication was achieved in 132 of the
      160 patients (82.5%) included in ITT analysis and 132 of the 157 patients (84%)
      included in PP analysis. In group B, H. pylori eradication was achieved in 18 of
      the 40 patients (45%) included in ITT analysis and 18 of the 38 patients (47.4%)
      included in PP analysis. Eradication rates were significantly higher in group A
      than in group B (P < 0.005). Eradication rates were not statistically significant
      between men and women in both groups. WHAT IS NEW AND CONCLUSION: Adding vitamins
      C and E to standard triple therapy increases the eradication rate of H. pylori.
      Vitamins C and E may increase the eradication rate via increasing the
      effectiveness of the antibiotics by decreasing oxidative stress in the gastric
      mucosa and strengthening the immune system.

PMID- 21740453
TI  - The [r]evolving relationship between risk assessment and risk management.
AB  - In Science and Decisions: Advancing Risk Assessment, the National Research
      Council recommends improvements in the U.S. Environmental Protection Agency's
      approach to risk assessment. The recommendations aim to increase the utility of
      these assessments, embedding them within a new risk-based decision-making
      framework. The framework involves first identifying the problem and possible
      options for addressing it, conducting related analyses, then reviewing the
      results and making the risk management decision. Experience with longstanding
      requirements for regulatory impact analysis provides insights into the
      implementation of this framework. First, neither the Science and Decisions
      framework nor the framework for regulatory impact analysis should be viewed as a
      static or linear process, where each step is completed before moving on to the
      next. Risk management options are best evaluated through an iterative and
      integrative procedure. The extent to which a hazard has been previously studied
      will strongly influence analysts' ability to identify options prior to conducting
      formal analyses, and these options will be altered and refined as the analysis
      progresses. Second, experience with regulatory impact analysis suggests that
      legal and political constraints may limit the range of options assessed, contrary
      to both existing guidance for regulatory impact analysis and the Science and
      Decisions recommendations. Analysts will need to work creatively to broaden the
      range of options considered. Finally, the usefulness of regulatory impact
      analysis has been significantly hampered by the inability to quantify many health
      impacts of concern, suggesting that the scientific improvements offered within
      Science and Decisions will fill an crucial research gap.

PMID- 21740454
TI  - Adrenergic and cardiac dysfunction in primary hyperparathyroidism.
AB  - OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with cardiovascular
      morbidity and premature death, but the underlying mechanisms are incompletely
      understood. The aim of this study was to investigate whether adrenergic
      dysfunction may be a contributing factor. PATIENTS AND METHODS: Forty-nine
      patients with mild PHPT (serum calcium 2.7 +/- 0.1 mM) and 48 control subjects,
      matched for age and sex, were examined; patients within 1 month before
      parathyroidectomy (PTX) and 6 months postoperatively; control subjects at
      inclusion. Heart rate variability (HRV) was analysed in 24-h electrocardiograms,
      and plasma concentrations of epinephrine and norepinephrine were measured at rest
      and immediately after standardized physical tests. RESULTS: At baseline, the
      patients showed, compared to the controls, reduced stress-related increase of
      circulating epinephrine (P < 0.05) and norepinephrine (P < 0.05). No significant
      change was observed 6 months after PTX. At baseline, there were no significant
      differences between patients and controls in HRV or heart rate, but 6 months
      after curative PTX, the patients showed significantly reduced HRV in both
      frequency and time domain, and their maximum and average heart rate had decreased
      (P = 0.011 and P = 0.018, respectively). The patients with the highest
      preoperative levels of circulating parathyroid hormone showed the greatest
      changes in heart rate and HRV postoperatively. CONCLUSIONS: This study
      demonstrates a previously unknown impairment of catecholamine response to
      physical stress in PHPT along with changes of HRV, also indicating adrenergic
      dysfunction. These factors should be considered in the ongoing controversy
      regarding the management of patients with mild 'asymptomatic' PHPT.

PMID- 21740455
TI  - Shear wave elastography in the diagnosis of thyroid nodules: feasibility in the
      case of coexistent chronic autoimmune Hashimoto's thyroiditis.
AB  - OBJECTIVE: ShearWaveTM Elastography (SWE) is real-time, quantitative and user
      independent technique, recently introduced in the diagnostic work-up of thyroid
      nodules. Hashimoto's thyroiditis (HT), characterized by variable degrees of
      lymphocytic infiltration and fibrosis, might affect shear wave propagation. The
      aim of this study was to assess the feasibility of SWE in cytologically benign
      thyroid nodules within both Hashimoto's and nonautoimmune thyroid glands. The
      effect of autoimmunity on the gland stiffness was also evaluated. DESIGN:
      longitudinal study in a single centre. PATIENTS: SWE was performed in 75 patients
      with a benign thyroid nodule at cytology: 33 with Hashimoto's thyroiditis (HT
      group) and 42 with uni- or multi-nodular goitre, negative for thyroid
      autoimmunity (non-HT group). RESULTS: The elasticity index (EI) of the extra
      nodular tissue was greater, though not statistically significant, in the HT than
      in the non-HT group (24.0 +/- 10.5 kPa vs 20.8 +/- 10.4 kPa; P = 0.206). However,
      the EI of extra-nodular tissue was related to the TPOAb titre in the HT group (P
      = 0.02) and was significantly higher in patients with HT receiving L-thyroxine
      than in the euthyroid subjects (P = 0.02). The EI of thyroid nodules was similar
      in HT and non-HT groups. In both groups, the stiffness of nodules was
      significantly higher than that of the embedding tissue. CONCLUSIONS: Our data
      indicate that SWE correctly defines the elasticity of thyroid nodules
      independently from the coexistence of autoimmune thyroiditis, always being able
      to differentiate nodular tissue from the surrounding parenchyma. In HT, the
      stiffness of extra-nodular tissue increases in relation to both the thyroid
      antibody titre and the degree of impairment of thyroid function.

PMID- 21740456
TI  - Evidence for visfatin as an independent predictor of endothelial dysfunction in
      polycystic ovary syndrome.
AB  - OBJECTIVE: Emerging evidence links adipocyte-secreted hormones, in particular
      adiponectin and visfatin, to cardiovascular pathology. Although adipocytokines
      dysregulation is common in polycystic ovary syndrome (PCOS) within the context of
      obesity and insulin resistance, their participation in the process of vascular
      injury remains elusive. DESIGN AND METHODS: This prospective, case-control study
      enrolled 102 young women (69 patients with PCOS and 33 eumenorrheic age-matched
      controls); serum adiponectin, resistin and visfatin, testosterone, SHBG, lipids,
      glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA
      IR) and high-sensitivity C-reactive protein (hs-CRP) were simultaneously measured
      in all participants. Body composition analysis was performed using dual X-ray
      absorptiometry. Endothelium impairment was assessed by carotid artery intimae
      media thickness (CIMT) and brachial artery flow-mediated vasodilatation (FMD),
      respectively. RESULTS: In PCOS, both univariate and multivariate analyses
      evidenced that circulating visfatin was significantly related to free
      testosterone (P = 0.024) and brachial artery FMD (P = 0.008; P < 0.01 in
      multivariate analyses). By every visfatin tertile, a stepwise decrease in FMD was
      observed in all and PCOS only (P = 0.036), not confounded by age, body mass
      index, total body fat mass, testosterone, SHBG or HOMA-IR. Multiple regression
      analysis retained visfatin and free testosterone as independent predictors of
      FMD, explaining about 20% of FMD variability. Adiponectin correlated with CIMT
      and hs-CRP, but the association was driven by age, body mass and body fat. No
      relationship between resistin and endothelial markers was found. CONCLUSION:
      Visfatin may be a candidate to play a role in the pathogenesis of endothelial
      dysfunction in PCOS, independently of additional risk factors.

PMID- 21740457
TI  - Sense of coherence and its relationship with oral health-related behaviour and
      knowledge of and attitudes towards oral health.
AB  - OBJECTIVE: To investigate the relationship between sense of coherence (SOC), oral
      health-related behaviour, knowledge of and attitudes towards oral health in an
      adult Swedish population. METHODS: A cross-sectional design with a stratified
      random sample of 910 individuals aged 20, 30, 40, 50, 60, 70 and 80 years were
      invited to the study, from Jonkoping, Sweden. The investigation used the Swedish
      short version of the SOC questionnaire comprising 13 items and self-reported
      questions about oral health habits and knowledge of and attitudes towards oral
      health. In addition, a self-report questionnaire to elicit demographic
      information was included. RESULTS: A total of 525 individuals, 261 men and 264
      women, answered all the 13-item SOC questions, which constituted the final number
      of the participants. After adjustment for all the sociodemographic factors
      included in the analysis, individuals with a stronger SOC had twice as high a
      chance of having healthier behaviour, including a lower frequency of snacks and
      drinks between meals, as well as a more positive attitude, such as the importance
      of having one's own teeth as one gets older, satisfaction with their own teeth,
      perceiving their teeth as good and no feeling of dental fear, compared with
      individuals with a poorer SOC. Moreover, SOC and a good knowledge of caries were
      significantly associated after adjustment for age and gender. CONCLUSIONS: SOC
      was significantly associated with several oral health-related behaviours,
      attitudes towards oral health and knowledge of dental caries. When working with
      oral health promotion, SOC could be a way for promoting a better understanding of
      the behaviour and attitudes of individuals and for enabling dental personals to
      use that knowledge for the guidance of the individual.

PMID- 21740458
TI  - Intradermal capsaicin as a neuropathic pain model in patients with unilateral
      sciatica.
AB  - AIM: This study compared the responses between patients with unilateral sciatica
      and pain-free volunteers following administration of intradermal capsaicin.
      METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers
      received one injection per hour over 4 h of 1 ug and 10 ug capsaicin, into each
      calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm2) and the
      sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre
      injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS: Sciatica
      subjects experienced higher spontaneous pain and hyperalgesia responses in both
      legs compared with pain-free volunteers. The largest mean difference in
      spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg
      following 10 ug. The largest mean difference in hyperalgesia was 19.7 cm (95% CI
      12.4, 27.0) at 60 min in the unaffected leg following 10 ug. Allodynia was
      greater in patients than in controls with the largest mean difference of 2.9 cm
      (95% CI 1, 4.8) at 5 min following 10 ug in the affected leg. Allodynia was also
      higher in the affected leg compared with the unaffected leg in sciatica patients
      with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following
      10 ug. CONCLUSIONS: The responses to intradermal capsaicin are quantitatively and
      qualitatively different in unilateral sciatica patients compared with pain-free
      controls.

PMID- 21740459
TI  - Health-related quality of life and post-traumatic stress disorder symptoms in
      accident and emergency attenders suffering from psychosocial crises: a
      longitudinal study.
AB  - AIMS: This paper is a report of a study of health-related quality of life and
      post-traumatic stress disorder symptoms in patients attending an Accident and
      Emergency department because of psychosocial crises. BACKGROUND: Psychosocial
      crises are commonplace globally, but there is little knowledge about patients
      attending Accident and Emergency departments because of psychosocial crises.
      METHODS: Data were collected at an Accident and Emergency department in Norway
      from September 2008 to June 2009. A total of 99 adults participated in the
      baseline study and 41 of these participated at 2 months follow-up. The Short Form
      36 Health Survey and the Post Traumatic Symptom Scale were used to obtain data.
      FINDINGS: Participants reported significantly lower scores in all health-related
      quality of life domains at baseline compared with the general Norwegian
      population. The mental health score was two standard deviations below the norm.
      Health-related quality of life scores were improved and post-traumatic stress
      disorder symptoms were reduced after 2 months. High levels of post-traumatic
      stress disorder symptoms were reported by 78% of the participants at baseline and
      59% at follow-up. Participants with high levels of post-traumatic stress disorder
      symptoms at follow-up also reported low health-related quality of life scores.
      CONCLUSION: This study suggests a need for an acute psychosocial intervention and
      an opportunity to receive follow-up support at Accident and Emergency
      departments.

PMID- 21740460
TI  - Impact of nurse agreeableness and negative mood of nursing supervisors on
      intention to help colleagues.
AB  - AIMS: This paper is a report of a correlational study of the relations of nurse
      agreeableness and negative supervisor mood to nurses' intentions to help their
      colleagues. BACKGROUND: Nursing collaboration is important to high quality care.
      Previous studies have identified agreeableness and negative mood of supervisors
      as influential factors in the workplace. In nursing, however, exactly how these
      factors and their interactions influence nurses' intention to help their
      colleagues remains unknown. METHODS: A cross-sectional design and questionnaires
      were used to collect data in December 2007. Each sample set comprised of one
      supervisor and three nurses. A total of 53 sets of questionnaires were
      distributed, and 46 complete sets of responses were received, yielding a response
      ratio of 86.8%. RESULTS: The analytical results indicate that nurse agreeableness
      is positively related to nurses' intentions to help colleagues (path coefficient
      = 0.54, P < 0.01). However, negative supervisor mood is negatively related to
      nurses' intentions to help colleagues (path coefficient = -0.13, P < 0.05).
      Moreover, the analytical results indicated that for highly agreeable nurses, the
      relationship between negative supervisor mood and nurses' intentions to help
      colleagues is significantly stronger than for less agreeable nurses. This
      demonstrates that nurse agreeableness amplifies the negative impact of negative
      supervisor mood on nurses' intentions to help colleagues. CONCLUSION: The study
      findings suggest the pivotal importance of managing negative supervisor mood to
      increase nurses' intentions to help colleagues.

PMID- 21740461
TI  - Bulky disease has an impact on outcomes in primary diffuse large B-cell lymphoma
      of the breast: a retrospective analysis at a single institution.
AB  - OBJECTIVES: Primary breast lymphoma (PBL) is rare, and its clinical behavior and
      standard initial treatment are not yet established. METHODS: We retrospectively
      analyzed the clinicopathological features and treatment outcomes of 14 patients
      with primary breast diffuse large B-cell lymphoma. RESULTS: There were nine
      patients with stage IE and five with stage IIE disease. The median largest tumor
      diameter was 4.5 cm, and five patients had bulky disease >5 cm. The complete
      response rate was 94%. However, the 5-year progression-free survival rate was 52%
      with a median follow-up of 5.2 years. Patients with bulky disease had an
      unfavorable prognosis. All five patients with bulky disease progressed or
      relapsed. Of the four patients that recurred in the central nervous system (CNS),
      three had bulky disease although some received rituximab. There were no CNS
      recurrences in the three patients who received CNS prophylaxis. All eight
      patients who responded to radiotherapy (RT) did not have recurrences in the
      ipsilateral breast, although one patient with bulky disease relapsed in the
      adjacent regional lymph nodes within the RT field despite immunochemotherapy.
      CONCLUSIONS: Patients with bulky disease had a poorer prognosis and recurred
      frequently in the CNS. CNS prophylaxis might yield better outcomes, but a larger,
      prospective trial is needed to elucidate the optimal initial treatment of PBL in
      the rituximab era.

PMID- 21740462
TI  - Oral administration of Escherichia coli Nissle 1917 prevents allergen-induced
      dermatitis in mice.
AB  - BACKGROUND: The prevalence of allergies has been linked to Western life style
      factors including a decrease of microbial exposure. Probiotics, such as
      Escherichia coli Nissle 1917 (EcN), have been shown to be beneficial for
      prevention and treatment of several chronic inflammatory diseases. OBJECTIVE: The
      aim of this study was to investigate the impact of oral EcN administration on
      development and outcome of allergen-induced dermatitis. METHODS: In sensitized
      BALB/c mice, skin inflammation was induced by topical allergen application. EcN
      was administered orally in a preventive manner. Severity of dermatitis was
      analysed by evaluation of skin score, local cellular and cytokine profile. The
      systemic immune response was assessed by analysis of immunoglobulins and allergen
      dependent cytokine response. RESULTS: Oral EcN administration improved allergen
      induced dermatitis dose-dependently. In parallel, a reduction of epidermal
      thickness and infiltrating immune cells together with an enhanced number of
      forkhead box P3 (Foxp3)(+) cells and a trend of increased IFNgamma, IL-10 and
      TGFbeta expression was detected in eczematous skin. In allergen-stimulated
      splenocytes reduced IL-4 and IFNgamma along with an elevated IL-10 production and
      a tendency to an increased TGFbeta secretion were observed. CONCLUSIONS: Our
      findings indicate that EcN alters the local allergen-induced immune response by
      increase of Foxp3(+) cells and by favouring an immunoregulatory cytokine pattern.
      Thus, oral administration of EcN might be an effective strategy in prevention and
      potentially therapy of allergic inflammatory skin diseases.

PMID- 21740463
TI  - Bullous cryothermic dermatitis artefacta induced by deodorant spray abuse.
AB  - BACKGROUND: Dermatitis artefacta belongs to a broad spectrum of factitious
      diseases of lesions usually self-induced by patients. Here we report a
      surprisingly effective induction of blisters and thermic dermatitis by excessive
      abuse of common deodorant sprays. OBJECTIVES: We evaluated the clinical course
      and outcome in three patients with dermatitis artefacta induced by deodorant
      spray. METHODS: A 12-year-old boy only admitted the abuse of deodorant spray
      after psychiatric intervention. Two adults (21-year-old and 37-year-old women)
      had borderline personality disorder and frankly reported the urge to induce pain
      by spraying for at least 100 s at a short distance. RESULTS: Bullous dermatitis
      was the acute presenting sign in all patients. The bullae were found on the
      extensor surfaces of the extremities, with a distribution of older lesions
      showing erosions and scarring and fresh lesions with intact bullae with a
      diameter of 3-15 cm. After searching for the causative agent and removal of the
      deodorant spray, clinical outcome showed a healing without and with scars.
      CONCLUSIONS: Cryo-damage by abuse of common deodorant sprays seems to become a
      popular mechanism by which an impressive bullous dermatitis can be artificially
      induced. Dermatologists and psychiatrist should be aware of this method of
      injury.

PMID- 21740464
TI  - Subcutaneous injection of liquid and foamed polidocanol: extravasation is not
      responsible for skin necrosis during reticular and spider vein sclerotherapy.
AB  - BACKGROUND: Cutaneous necrosis is one of the most annoying complications of
      reticular and spider vein sclerotherapy. The precise incidence of the
      complication is not known, although various sources reported incidence between
      0.2% and 1.2%. Among a few mechanisms proposed to explain it, extravasation of
      the sclerosant into the perivascular tissue has been cited as the major cause.
      OBJECTIVES: The aim of the experimental study in rats was to examine the
      potential of various concentrations and volumes of polidocanol in both liquid and
      foam forms to cause cutaneous necrosis after superficial subcutaneous injection.
      METHODS: Twenty-four female Sprague Dawley rats were injected subcutaneously
      different concentrations (0.5%, 1%, 2% and 3%) of polidocanol as well as
      different preparations of polidocanol (liquid vs. foam) and volumes (0.1-0.5 mL).
      The animals were sacrificed 10 days after injections and biopsy specimens were
      obtained. RESULTS: Cutaneous necrosis was not seen at volumes <0.5 mL regardless
      of the concentration or form of polidocanol injected. Foam preparation was shown
      to be less potent in inducing necrosis with a minimal strength being 2% in
      comparison with the liquid form where 1% was sufficient to produce overt
      cutaneous necrosis. CONCLUSIONS: This experimental study shows that extravasation
      of polidocal in usual circumstances of sclerotherapy of spider and reticular
      veins cannot be a significant cause of cutaneous necrosis rarely observed in this
      setting. It is particularly true for the foamed polidocanol where 1% strength
      seems safe if injected extravascularly in volumes up to 0.5 mL.

PMID- 21740465
TI  - Teledermatology with an integrated nurse-led clinic on the Faroe Islands--7
      years' experience.
AB  - BACKGROUND: Telemedicine is an increasingly suggested answer to the problem of
      providing high-class medical service to rural and remote areas in a modern
      society. Dermatology is a promising candidate for telemedical service, because it
      is well suited for clinical questions forwarded together with photographs.
      OBJECTIVES: To describe the patient population of the Faroe Islands dermatology
      clinic with respect to distribution of diagnoses, treatment, duration, response
      time and patient flow. METHODS: Case notes were drawn from all dermatology
      consultations managed during 2003-2009 through the national teledermatology
      system. These were compared with case notes drawn from the same journal system
      from the regular outpatient clinic. RESULTS: Over the last 7 years, a total of
      9161 consultations in 7.7% of the population have been performed. The demography
      of the patient population reflects the underlying population apart for an over
      representation of the female gender in younger years. The disease spectrum is
      comparable with what has been reported in other outpatient clinics, except for
      the relative absence of skin cancer and pigmented lesions, for which regular
      outpatient consultation is reserved. LIMITATIONS: The study is descriptive.
      CONCLUSIONS: The experience derived suggests that teledermatology may serve as a
      near-adequate alternative to a regular private practice, if abstaining from
      treating minor common skin conditions and purely cosmetic conditions is
      acceptable.

PMID- 21740466
TI  - Effectiveness of photodynamic therapy in Bowen's disease: an observational and
      descriptive study in 51 lesions.
AB  - INTRODUCTION: Bowen disease (BD) or squamous cell carcinoma (SCC) in situ affects
      both skin and mucous membranes and has the potential to progress to invasive SCC.
      Photodynamic therapy (PDT) has been approved recently for the treatment of BD.
      Some studies have demonstrated its efficacy and good cosmetic outcome. OBJECTIVE:
      To assess the efficacy of PDT in the treatment of BD. PATIENTS AND METHODS: We
      carried out an observational, retrospective and descriptive study. A total of 47
      patients with 51 lesions of BD were included. All the lesions were confirmed with
      previous cutaneous biopsy. All patients were treated with the standard protocol.
      Topical methyl-aminolaevulinic acid was occluded during 3 h and followed by
      illumination with red-light (630 nm, 38 J/cm2, 7.5 min). Clinical and
      fluorescence photographs images were taken before each session. All patients
      received two sessions one week apart. Clinical response was classified in partial
      or complete response. Fluorescence response was classified in negative,
      intermediate or intense. The follow-up period and the adverse events observed
      including pain were also collected. RESULTS: A total of 20 men and 27 women with
      a mean age of 75.57 years old were treated with PDT. Lesions were most frequently
      located in the lower limbs. Globally, 76.09% of the lesions achieved complete
      response after 2 sessions with a medium follow-up of 16.61 months. Fluorescence
      of the lesions disappeared when clinical response was achieved, but not always.
      The most common adverse effect was an immediate burning sensation. All lesions
      showed an excellent cosmetic result. CONCLUSION: Photodynamic therapy is an
      effective treatment for BD in terms of both clinical remission and cosmetic
      results, with good tolerance and minimal adverse effects.

PMID- 21740467
TI  - Effects of dietary fat levels on nutrient digestibility and production
      performance of growing-furring blue foxes (Alopex lagopus).
AB  - The objective of this study was to determine whether nutrient digestibility and
      production performance of growing-furring blue foxes (Alopex lagopus) are
      affected by different dietary fat levels. Sixty-four young animals were randomly
      assigned to four groups (A, B, C, D) provided with diets containing approximately
      12%, 26%, 40%, 54% fat in the dry matter respectively. When dietary fat level was
      increased, the apparent digestibility of main nutrients except for crude
      carbohydrates, and gross energy were improved (p < 0.0001). The amount of
      nitrogen excreted was reduced and the biological value of protein was enhanced (p
      < 0.0001). Over the experimental phase, the efficiency of metabolizable energy
      (ME) used for gain in group B (26% fat content) was higher than that in other
      groups. When diets with 12-26% fat content were fed, there was an increasing
      tendency in skin size. But it had negative effects on skin size and fur quality
      when the amount of fat content was over 40%. In conclusion, the experiment showed
      that dietary fat could significantly improve some nutrient utilization and
      significantly reduce feed/gain ratio as a main energy source. The most preferable
      fur quality and efficiency of ME used for gain were obtained when diet contained
      26% fat level in growing-furring period.

PMID- 21740468
TI  - The effect of depurinized milk draught diet on rat serum uric acid, lipid status
      and haematological parameters.
AB  - Hyperuricaemia and gout are closely related, but hyperuricaemia is an independent
      risk factor for endothelial damage, autoinflammation and haemodynamic
      abnormalities. Milk, generally known as a 'purine-free diet', is an essential
      protein source for patients suffering from hyperuricaemia and gout. As milk still
      contains different purine ribonucleotides, the new product, depurinized milk,
      almost free of purine nucleotides and uric acid, was produced. The potential
      effect of depurinized milk diet on serum uric acid (SUA) level, lipid parameters
      and blood haematological parameters was explored in rats after 72 h and 15 days,
      in relation to standard laboratory chow or the untreated milk diet. The
      beneficial effect on SUA was achieved when depurinized milk draught was given
      instead of standard chow for 72 h [28.39 +/- 4.76 MUm; p < 0.001 vs. standard
      diet (STD) 47.6 +/- 6.12, vs. untreated milk diet 31.55 +/- 8.50; p < 0.05] or as
      a supplement for STD for 15 days experiment (35.38 +/- 6.40 MUm; p < 0.05 vs. STD
      only 48.05 +/- 4.32; vs. untreated milk + STD 46.02 +/- 9.48). Depurinized milk
      diet significantly decreased the low density lipoproteins/high density
      lipoproteins (LDL/HDL) ratio (p < 0.001), triglycerides (p < 0.05) and leucocyte
      count (p < 0.001), while both milk draughts enhanced haemoglobin concentration (p
      < 0.01). In conclusion, considering the detrimental effect of persisting
      hyperuricaemia, the depurinized milk draught may meet the demand of healthy dairy
      product for population under hyperuricaemic risk.

PMID- 21740469
TI  - Epidemiological and clinico-mycological profile of fungal wound infection from
      largest burn centre in Asia.
AB  - The current study was conducted to know the incidence, predisposing factors,
      spectrum, clinical profile and antifungal susceptibility (AFS) of fungal wound
      infection (FWI) in burn patients. Of a total of 71 patients, 20 (28.2%) emerged
      with the diagnosis of FWI. Fungal pathogens in this study were Candida tropicalis
      (14%), Candida parapsilosis (5.6%), Aspergillus niger (2.8%) and one each of
      Candida albicans (1.4%), Candida glabrata (1.4%), Syncephalestrum (1.4%) and
      Fusarium solani (1.4%). All patients with mould infections expired before the
      mycological culture results could be conveyed to clinicians. Of the yeasts
      isolated in the study, one each of C. tropicalis and C. albicans showed cross
      resistance to azoles. All the moulds were susceptible to amphotericin B. This
      study depicted that fungal invasion is associated with a high mortality, burn
      size 30-60% and high incidence of inhalational injury. Fungal invasion was
      detected on an average of 14 days after injury. Association of use of four
      classes of drugs - aminoglycosides, imipenem, vancomycin and third generation
      cephalosporins and use of total parenteral nutrition was observed. Expedient
      laboratory diagnosis of FWI and appropriate systemic antifungal therapy guided by
      AFS may improve outcome for severely injured burn victims.

PMID- 21740470
TI  - Liver transplantation and spontaneous neovascularization after arterial
      thrombosis: "the neovascularized liver".
AB  - The only arterial pathway available after liver transplantation is the hepatic
      artery. Therefore, hepatic artery thrombosis can result in graft loss
      necessitating re-transplantation. Herein, we present evidence of
      neovascularization at long-term follow-up in a series of transplant patients with
      hepatic artery thrombosis. We termed this phenomenon "neovascularized liver".
      Hepatic artery thrombosis was noted in 30/407 cases (7.37%), and occurred early
      in 13 patients (43.3%) and late (>30 days) in 17 (56.7%) patients. At the time of
      this study, 11 (36.7%) patients had a neovascularized liver. Those patients with
      neovascularized liver and normal liver function were closely followed. Of these
      patients, 10 (91%) showed evidence of neovascularized liver by imaging, and an
      echo-Doppler arterial signal was recorded in all patients. The mean interval
      between the diagnosis of hepatic artery thrombosis and neovascularized liver was
      4.1 months (range of 3-5.5 months). Liver histology showed an arterial structure
      in 4 (36.4%) patients. Four factors were associated with development of
      neovascularized liver: late hepatic artery thrombosis, early hepatic artery
      stenosis, site of thrombosis, and Roux-en-Y anastomosis. The overall survival
      rate at 54 months was 90.9%. In conclusion, a late hepatic artery thrombosis may
      be quite uneventful and should not automatically lead to re-transplantation.

PMID- 21740471
TI  - The spectrum of nonadherence with medication in heart, liver, and lung transplant
      patients assessed in various ways.
AB  - Adherence to medication regimes is crucial for transplant patients. Addressing
      methodological limitations and gaps in the literature, we studied: (i) the
      prevalence of nonadherence (NA) with immunosuppression (IS) using various
      measurement methods, (ii) NA prevalence regarding intake and timing, (iii)
      changes in NA over time, (iv) differences in NA across organ transplant
      populations, (v) NA regarding co-medication. Using a descriptive, prospective,
      comparative design over 3 months, we included convenience samples of adult heart
      (n=79), liver (n=55), and lung (n=104) transplant patients. NA with IS was
      measured using self-report, collateral report, blood assay, electronic monitoring
      (Helping HandTM , Bang and Olufsen Medicom, Denmark), and their combinations. In
      the overall sample, depending on the method used, IS NA ranged from 23.9% to
      70.0%. For co-medication, the overall NA rate was 30.1% using self-report.
      Nonadherence rates remained stable over time. At inclusion, significant NA
      differences between organ groups were reported via self- and collateral report;
      lung transplant patients were less adherent than heart or liver transplant
      recipients, both to IS and to co-medication.

PMID- 21740472
TI  - Factors associated with reaching 90 years of age: a study of men born in 1913 in
      Gothenburg, Sweden.

PMID- 21740473
TI  - Reliability of panoramic radiographs for identifying supernumerary teeth in
      children.
AB  - OBJECTIVES. To evaluate the reliability of panoramic radiographs (PRs) for
      identifying supernumerary teeth (ST) and to determine whether the level of dental
      training of the observer influenced the identification of ST. METHODS. Seventy
      five PRs were randomly selected from the patient records and 18 examiners
      independently rated 25 radiographs each, for specific risk factors as well as for
      a measure of adequacy. Subsequently, the results were paired with those of the
      other examiners who assessed the same set of PRs. Descriptive statistics were
      computed using Fisher's exact test, and kappa statistics were used to assess the
      inter- and intra-observer reliability. RESULTS. Four hundred and fifty PRs were
      available for analysis. The overall sensitivity and specificity figures were 50%
      and 98.3%, whereas the positive and negative predictive values were 90.6% and
      83.6%, respectively. The sensitivity figures for Junior House Dental Officers and
      Postgraduate Paediatric Dental Trainees were 39.2% and 60.8%, whereas the
      specificity figures were 99.4% and 95% with slight inter-examiner and moderate
      intra-examiner reliability. CONCLUSIONS. Panoramic radiographs are unreliable for
      identifying ST, and higher level of dental training is essential for identifying
      ST.

PMID- 21740474
TI  - Time-dependent rates of molecular evolution.
AB  - For over half a century, it has been known that the rate of morphological
      evolution appears to vary with the time frame of measurement. Rates of
      microevolutionary change, measured between successive generations, were found to
      be far higher than rates of macroevolutionary change inferred from the fossil
      record. More recently, it has been suggested that rates of molecular evolution
      are also time dependent, with the estimated rate depending on the timescale of
      measurement. This followed surprising observations that estimates of mutation
      rates, obtained in studies of pedigrees and laboratory mutation-accumulation
      lines, exceeded long-term substitution rates by an order of magnitude or more.
      Although a range of studies have provided evidence for such a pattern, the
      hypothesis remains relatively contentious. Furthermore, there is ongoing
      discussion about the factors that can cause molecular rate estimates to be
      dependent on time. Here we present an overview of our current understanding of
      time-dependent rates. We provide a summary of the evidence for time-dependent
      rates in animals, bacteria and viruses. We review the various biological and
      methodological factors that can cause rates to be time dependent, including the
      effects of natural selection, calibration errors, model misspecification and
      other artefacts. We also describe the challenges in calibrating estimates of
      molecular rates, particularly on the intermediate timescales that are critical
      for an accurate characterization of time-dependent rates. This has important
      consequences for the use of molecular-clock methods to estimate timescales of
      recent evolutionary events.

PMID- 21740475
TI  - DOG1 expression is predicted by the seed-maturation environment and contributes
      to geographical variation in germination in Arabidopsis thaliana.
AB  - Seasonal germination timing of Arabidopsis thaliana strongly influences overall
      life history expression and is the target of intense natural selection. This
      seasonal germination timing depends strongly on the interaction between genetics
      and seasonal environments both before and after seed dispersal. DELAY OF
      GERMINATION 1 (DOG1) is the first gene that has been identified to be associated
      with natural variation in primary dormancy in A. thaliana. Here, we report
      interaccession variation in DOG1 expression and document that DOG1 expression is
      associated with seed-maturation temperature effects on germination; DOG1
      expression increased when seeds were matured at low temperature, and this
      increased expression was associated with increased dormancy of those seeds.
      Variation in DOG1 expression suggests a geographical structure such that southern
      accessions, which are more dormant, tend to initiate DOG1 expression earlier
      during seed maturation and achieved higher expression levels at the end of
      silique development than did northern accessions. Although elimination of the
      synthesis of phytohormone abscisic acid (ABA) results in the elimination of
      maternal temperature effects on dormancy, DOG1 expression predicted dormancy
      better than expression of genes involved in ABA metabolism.

PMID- 21740476
TI  - Modifiable lifestyle and environmental risk factors affecting the retinal
      microcirculation.
AB  - Structural changes within the human retinal vasculature may reflect systemic
      vascular changes associated with various cardiovascular and metabolic disorders.
      Recent data suggest that systemic exposure from a range of modifiable lifestyle
      and environmental risk factors (e.g., diet, physical activity, and smoking) may
      affect the morphology of the retinal vasculature. Being easily accessible and non
      invasively visualized, the retinal microvasculature therefore can be a clinically
      useful biomarker of reversible sub-clinical physiologic deviation of the systemic
      circulation as results of such unfavorable exposures. Importantly, quantitative
      analysis of the retinal microvasculature may be utilized as a prognostic tool,
      allowing for targeted vascular therapies before the onset of overt cardiovascular
      and metabolic disorders. This review summarizes the modifiable lifestyle and
      environmental risk factors that affect retinal microvascular structure and the
      possible clinical implications of such relationships.

PMID- 21740477
TI  - Side population cells isolated from human osteosarcoma are enriched with tumor
      initiating cells.
AB  - It has been proven that "side population (SP)" cells that exclude Hoechst 33342
      dye are enriched with cancer stem cells in several tumors. In the present study
      we aimed to isolate and characterize SP cells from human primary osteosarcoma.
      Side population cells were detected in osteosarcoma samples. In vitro, SP cells
      regenerated both SP and non-SP and the clonogenicity of SP cells was higher than
      that of non-SP cells, just like stem cells. In vivo, SP cells exhibited
      heightened tumorigenicity and only the SP fraction had the capacity to self-
      renew both in vitro and in vivo. Furthermore, SP cells exhibited increased
      multidrug resistance and the RNA expression of ATP-binding cassette protein
      transporters was increased in the SP group. In addition, "stemness" genes Oct-4
      and Nanog were also upregulated in the SP group. However, the expression of other
      putative stem cell markers (CD44, CD117 and CD133) had no significant difference
      between SP and non-SP for each individual marker. These findings suggest that SP
      cells derived from osteosarcoma are enriched with tumorigenic cells with stem
      like properties and might be an ideal target for clinical therapy.

PMID- 21740478
TI  - Genotype-directed, dose-finding study of irinotecan in cancer patients with
      UGT1A1*28 and/or UGT1A1*6 polymorphisms.
AB  - Irinotecan-induced severe neutropenia is associated with homozygosity for the
      UGT1A1*28 or UGT1A1*6 alleles. In this study, we determined the maximum-tolerated
      dose (MTD) of irinotecan in patients with UGT1A1 polymorphisms. Patients who had
      received chemotherapy other than irinotecan for metastatic gastrointestinal
      cancer were enrolled. Patients were divided into three groups according to UGT1A1
      genotypes: wild-type (*1/*1); heterozygous (*28/*1, *6/*1); or homozygous
      (*28/*28, *6/*6, *28/*6). Irinotecan was given every 2 weeks for two cycles. The
      wild-type group received a fixed dose of irinotecan (150 mg/m(2)) to serve as a
      reference. The MTD was guided from 75 to 150 mg/m(2) by the continual
      reassessment method in the heterozygous and homozygous groups. Dose-limiting
      toxicity (DLT) and pharmacokinetics were evaluated during cycle 1. Of 82 patients
      enrolled, DLT was assessable in 79 patients (wild-type, 40; heterozygous, 20; and
      homozygous, 19). Dose-limiting toxicity occurred in one patient in the wild-type
      group, none in the heterozygous group, and six patients (grade 4 neutropenia) in
      the homozygous group. In the homozygous group, the MTD was 150 mg/m(2) and the
      probability of DLT was 37.4%. The second cycle was delayed because of neutropenia
      in 56.3% of the patients given the MTD. The AUC(0-24 h) of SN-38 was
      significantly greater (P < 0.001) and more widely distributed in the homozygous
      group. Patients homozygous for the UGT1A1*28 or UGT1A1*6 allele can receive
      irinotecan in a starting dose of 150 mg/m(2), but many required dose reductions
      or delayed treatment in subsequent cycles. UMIN Clinical Trial Registration
      number: UMIN000000618.

PMID- 21740479
TI  - IKZF1 deletions predict a poor prognosis in children with B-cell progenitor acute
      lymphoblastic leukemia: a multicenter analysis in Taiwan.
AB  - Despite current risk-directed therapy, approximately 15-20% of pediatric patients
      with acute lymphoblastic leukemia (ALL) have relapses. Recent genome-wide
      analyses have identified that an alteration of IKZF1 is associated with very poor
      outcomes in B-cell progenitor ALL. In this study, we determined the prognostic
      significance of IKZF1 deletions in patients with childhood ALL. This study
      analyzed 242 pediatric B-cell progenitor ALL patients in Taiwan. We developed a
      simple yet sensitive multiplex quantitative PCR coupled with capillary
      electrophoresis to accurately determine the allele dose of IKZF1, and high
      resolution melting was used for mutation screening for all coding exons of IKZF1.
      Twenty-six (10.7%) pediatric B-cell progenitor ALL patients were found to harbor
      these deletions. Most of the deletions were broader deletions that encompassed
      exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1
      was carried out in all cases and no point mutations were identified. Patients
      with IKZF1 deletions had inferior event-free survival (P < 0.001), and overall
      survival (P = 0.0016). The association between IKZF1 deletions and event-free
      survival was independent of age, leukocyte count at presentation, and cytogenetic
      subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study
      indicates that detection of IKZF1 deletions upon diagnosis of B-cell progenitor
      ALL may help to identify patients at risk of treatment failure. IKZF1 deletions
      could be incorporated as a new high-risk prognostic factor in future treatment
      protocols. To the best of our knowledge, this is the first study to examine the
      poor prognosis of IKZF1 deletions in an Asian population.

PMID- 21740480
TI  - Differences in Kaposi sarcoma-associated herpesvirus-specific and herpesvirus-non
      specific immune responses in classic Kaposi sarcoma cases and matched controls in
      Sicily.
AB  - Kaposi sarcoma (KS) might develop because of incompetent immune responses, both
      non-specifically and specifically against the KS-associated herpesvirus (KSHV).
      Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV
      seropositives (without KS) and 15 KSHV-seronegative controls were tested for
      interferon-gamma T-cell (enzyme-linked immunospot [Elispot]) responses to KSHV
      latency-associated nuclear antigen (LANA), KSHV-K8.1 and CMV/Epstein-Barr virus
      (EBV) peptide pools. The forearm and thigh of each participant was also tested
      for delayed-type hypersensitivity (DTH) against common recall antigens. Groups
      were compared with Fisher exact test and multinomial logistic regression to
      calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot
      response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives
      (without KS) and two (13%) seronegative controls. All four cases with KSHV-LANA
      responses had current KS lesions, whereas five of six cases with KSHV-K8.1
      responses had no lesions (P = 0.048). No case responded to both LANA and K8.1.
      Compared with the seronegative controls, the risk for classic KS was inversely
      related to DTH in the thigh (OR 0.71, 95% CI 0.55-0.94, P = 0.01), directly
      associated with DTH in the forearm (OR 1.35, 95% CI 1.02-1.80, P = 0.04) and
      tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86
      30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for
      classic KS was reduced fivefold (OR 0.20, CI 0.03-0.77, P = 0.04) per KSHV
      response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV
      specific and KSHV-non-specific immunity is associated with classic KS. This might
      clarify why Kaposi sarcoma responds to immune reconstitution.

PMID- 21740481
TI  - Systemic cytokine levels and subsequent risk of gastric cancer in Chinese Women.
AB  - Although control of the host cytokine network is known to influence gastric
      cancer susceptibility, the specific inflammatory responses in gastric
      carcinogenesis remain unclear. We prospectively examined the relationships
      between gastric cancer risk and plasma levels of interleukin (IL)-1beta, IL-6, IL
      8 and tumor necrosis factor (TNF)-alpha in a nested case control study within The
      Shanghai Women's Health Study. Two controls were matched to each case on the
      basis of age, menopausal status, and sample collection parameters. The
      associations between gastric cancer risk and tertiles of cytokine levels were
      estimated by odds ratios (OR) and 95% confidence intervals (CI) from conditional
      logistic regression, adjusting for education. During a median follow-up period of
      4 years (range 0.1-8 years), 141 women developed gastric cancer and were matched
      to 282 cancer-free study participants. Elevated levels of plasma IL-6 were
      associated with an increased risk of gastric cancer (P(trend) = 0.04). Risk
      increased 70% (OR = 1.7; 95% CI 1.0, 3.0) for women in the highest tertile (>4
      pg/mL) of IL-6 compared with those in the lowest tertile (<1.8 pg/mL). The
      association between gastric cancer risk and IL-6 was stronger after 4 years of
      follow-up (OR = 2.6 [95% CI 1.0, 6.7] for highest versus lowest tertile) compared
      with an OR of 1.4 (95% CI 0.7, 2.9) for those diagnosed within 1-4 years of
      follow-up. No associations were observed with the other pro-inflammatory
      cytokines examined, namely IL-1beta, IL-8, and TNF-alpha. Systemic plasma IL-6
      levels may inform long-term gastric cancer risk. This novel finding awaits
      confirmation in future studies with sequential plasma collection.

PMID- 21740482
TI  - Inter-observer reproducibility and analysis of gastric volume measurements and
      gastric emptying assessed with magnetic resonance imaging.
AB  - BACKGROUND: Magnetic resonance (MR) imaging provides direct, non-invasive
      measurements of gastric function and emptying. The inter-observer variability
      (IOV) of MR volume measurements and the most appropriate analysis of MR data have
      not been established. To assess IOV of total gastric volume (TGV) and gastric
      content volume (GCV) measurements from MR images and the ability of standard
      power exponential (PowExp), and a novel linear exponential (LinExp) model to
      describe MR data. METHODS:   Ten healthy volunteers received three different
      volumes of a liquid nutrient test meal (200-800 mL) on 3 days in a randomized
      order. Magnetic resonance scans were acquired using a 1.5T system every 1-5 min
      for 60 min. Total gastric volume and GCV were measured independently by three
      observers. Volume data were fitted by PowExp and LinExp models to assess
      postprandial volume change and gastric emptying half time (T(50) ). KEY RESULTS:
      An initial rise in GCV and TGV was often observed after meal ingestion,
      thereafter GCV and TGV decreased in an approximately linear fashion. Inter
      observer variability decreased with greater volumes from 12% at 200 mL to 6% at
      600 and 800 mL. Inter-observer variability for T(50) was <5%. PowExp and LinExp
      models provided comparable estimates of T(50) ; however, only LinExp described
      dynamic volume change in the early postprandial period. CONCLUSIONS & INFERENCES:
      Gastric MR provides quantitative measurements of postprandial volume change with
      low IOV, unless the stomach is nearly empty. The novel LinExp model describes the
      dynamic volume changes in the early postprandial period more accurately than the
      PowExp model used in existing gastric emptying studies.

PMID- 21740483
TI  - Factors influencing dyspepsia-related consultation: differences between a rural
      and an urban population.
AB  - BACKGROUND: Dyspepsia is a common, chronic condition but medical consultation
      rates for symptoms remain variable. We aimed to examine two populations with
      varied health-care provision to determine predictive factors for dyspepsia
      related consultation. METHODS: A cross-sectional, population-based study in both
      an urban and a rural community within a single Asian country was conducted.
      Details on dyspepsia-related consultation rates over a fixed period and
      independent factors influencing them were identified. KEY RESULTS: A total of
      4039/5370 (75.2%) adults from representative rural and urban areas in this
      country agreed to participate in the study. Although mean ages of respondents
      were similar (40.4years), the demographics of both populations varied in terms of
      gender (62.7% female, rural vs 55.7% female, urban, P<0.0001), marital status
      (75.4% rural vs 70.5% urban, P=0.002), ethnicity, (79% Malay rural vs 45.3%
      Malays urban, P<0.0001) and socio-economic status (professional occupation 7.1%
      rural vs 47.3% urban, P<0.0001). Dyspepsia-related consultation rates were found
      to be higher among rural compared to urban adults (41.4%vs 28.7%, P<0.0001). Over
      the-counter medication consumption was higher among urban compared to rural
      dyspepsia sufferers (n=157 vs n=35, P<0.0001). Following logistic regression,
      rural population (OR 3.14, 95% CI=1.65-6.0), low quality of life (OR 1.90, 95%
      CI=1.17-3.10), and self-medication (OR 0.40, 95% CI=0.25-0.62) were found to
      independently predict dyspepsia-related consultation. CONCLUSIONS & INFERENCES:
      Dyspepsia-related consultation varied significantly between urban and rural
      communities. Factors within the rural population, self-medication practices, and
      a low quality of life independently influenced dyspepsia-related consultation.

PMID- 21740484
TI  - Two de novo factor VIII gene mutations in the family of an isolated severe
      haemophilia A patient.

PMID- 21740485
TI  - Efficacy of tongue protector in patients with burning mouth syndrome: a
      commentary.

PMID- 21740486
TI  - Synergistic requirement of orphan nonamer-like elements and DNA bending enhanced
      by HMGB1 for RAG-mediated nicking at cryptic 12-RSS but not authentic 12-RSS.
AB  - V(D)J recombination is initiated by the specific binding of the recombination
      activating gene (RAG) complex to the heptamer and nonamer elements within
      recombination signal sequence (RSS). The break points associated with some
      chromosomal translocations contain cryptic RSSs, and mistargeting of RAG proteins
      to these less conserved elements could contribute to an aberrant V(D)J
      recombination. Recently, we found RAG-dependent recombination in the hotspots of
      TEL-AML1 t(12;21)(p13;q22) chromosomal translocation by an extrachromosomal
      recombination assay. Here, we describe using in vitro cleavage assays that RAG
      proteins directly bind to and introduce nicks into TEL and AML1 translocation
      regions, which contain several heptamer-like sequences. The cryptic nicking site
      within the TEL fragment was cleaved by RAG proteins essentially depending on a 12
      RSS framework, and the nicking activity was enhanced synergistically by both
      HMGB1 and orphan nonamer-like (NL) sequences, which do not possess counterpart
      heptamers. In addition, we found that DNA bending stimulated by HMGB1 is
      indispensable for the HMGB1- and orphan NL element-dependent enhancement of RAG
      mediated nicking at the cryptic 12-RSS. Collectively, we would propose the
      mechanism of HMGB1-dependent enhancement of RAG-mediated nicking at a cryptic RSS
      through enhanced DNA bending.

PMID- 21740487
TI  - Administrative practices of health professionals and use of artesunate
      amodiaquine by community members for treating uncomplicated malaria in southern
      Ghana: implications for artemisinin-based combination therapy deployment.
AB  - OBJECTIVE: To investigate the use of artemisinin-based combination and
      monotherapy by community members and the administrative practices of health
      professionals in treating malaria in Ghana. METHOD: This study is a community
      based cross-sectional survey in 11 rural and urban areas in southern Ghana. Using
      the interviewer method, close-ended questionnaires were administered to community
      members. Similar questionnaires were also administered in health facilities,
      community pharmacies and licensed chemical shops. RESULTS: A total of 1085
      individuals comprising 959 non-health professionals and 126 health professionals
      were interviewed. Fifty-seven per cent of the community members visit
      pharmacies/drug stores as the first point of call when they suspect malaria.
      According to the participating drug sellers, artemether-lumefantrine (AL) is the
      most prescribed/sold anti-malarial drug (59.2%), followed by dihydroartemisinin
      (35%), sulfadoxine-pyrimethamine (33.0%) and artesunate-amodiaquine (AS-AQ)
      (27.2%). The majority of customers who visit pharmacies or drug stores without
      prescription have their anti-malarial drug selected by the shop attendant; in
      situations like that, dihydroartemisinin and artesunate monotherapies are sold
      just as AS-AQ and AL. Chloroquine is still sold by some drug vendors, 5 years
      after its proscription. CONCLUSION: Whereas the use of AS-AQ and AL are
      acceptable, the frequent use of dihydroartemisinin and artesunate monotherapy
      threatens the future of ACTs.

PMID- 21740488
TI  - Susceptibility of bacterial isolates from community-acquired infections in sub
      Saharan Africa and Asia to macrolide antibiotics.
AB  - OBJECTIVE: To review the literature on the susceptibility of common community
      pathogens in sub-Saharan Africa and Asia to the macrolide antibiotics. METHODS:
      Inclusion criteria required that isolates were collected since 2004 to ensure
      results were of contemporary relevance. The data were aggregated by region, age
      group and sterility of site of culture sample. RESULTS: A total of 51 studies
      were identified, which reported the macrolide antimicrobial susceptibilities of
      common bacterial pathogens isolated since 2004. In general, there was less
      macrolide resistance in African than in Asian isolates. Most African studies
      reported high levels of macrolide susceptibility in Streptococcus pneumoniae,
      whereas most Chinese studies reported high levels of resistance. There was very
      little information available for Gram-negative organisms. CONCLUSIONS:
      Susceptibility of the pneumococcus to macrolides in SSA remains high in many
      areas, and good activity of azithromycin has been shown against Salmonellae spp.
      in Asia. In urban areas where high antibiotic consumption is prevalent, there was
      evidence of increased resistance to macrolides. However, there is no information
      on susceptibility from large areas in both continents.

PMID- 21740489
TI  - Comparison of Campylobacter jejuni isolates from human, food, veterinary and
      environmental sources in Iceland using PFGE, MLST and fla-SVR sequencing.
AB  - AIMS: Campylobacter jejuni isolates from various sources in Iceland were
      genotyped with the aim of assessing the genetic diversity, population structure,
      source distribution and campylobacter transmission routes to humans. METHODS AND
      RESULTS: A collection of 584 Campylobacter isolates were collected from clinical
      cases, food, animals and environment in Iceland in 1999-2002, during a period of
      national Campylobacter epidemic in Iceland. All isolates were characterized by
      pulse field gel electrophoresis (PFGE), and selected subset of 52 isolates
      representing the diversity of the identified PFGE types was further genotyped
      using multilocus sequence typing (MLST) and fla-SVR sequencing to gain better
      insight into the population structure. CONCLUSIONS: The results show a
      substantial diversity within the Icelandic Campylobacter population. Majority of
      the human Campylobacter infections originated from domestic chicken and cattle
      isolates. MLST showed the isolates to be distributed among previously reported
      and common sequence type complexes in the MLST database. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The genotyping of Campylobacter from various sources has not
      previously been reported from Iceland, and the results of the study gave a
      valuable insight into the population structure of Camp. jejuni in Iceland, source
      distribution and transmission routes to humans. The geographical isolation of
      Iceland in the north Atlantic provides new information on Campylobacter
      population dynamics on a global scale.

PMID- 21740490
TI  - The role of VAMP7/TI-VAMP in cell polarity and lysosomal exocytosis in vivo.
AB  - VAMP7 or tetanus neurotoxin-insensitive vesicle- associated membrane protein (TI
      VAMP) has been proposed to regulate apical transport in polarized epithelial
      cells, axonal transport in neurons and lysosomal exocytosis. To investigate the
      function of VAMP7 in vivo, we generated VAMP7 knockout mice. Here, we show that
      VAMP7 knockout mice are indistinguishable from control mice and display a similar
      localization of apical proteins in the kidney and small intestine and a similar
      localization of axonal proteins in the nervous system. Neurite outgrowth of
      cultured mutant hippocampal neurons was reduced in mutant neurons. However,
      lysosomal exocytosis was not affected in mutant fibroblasts. Our results show
      that VAMP7 is required in neurons to extend axons to the full extent. However,
      VAMP7 does not seem to be required for epithelial cell polarity and lysosomal
      exocytosis.

PMID- 21740491
TI  - Myosin Va acts in concert with Rab27a and MyRIP to regulate acute von-Willebrand
      factor release from endothelial cells.
AB  - Von-Willebrand factor (vWF) is a highly multimerized hemostatic glycoprotein that
      is stored in endothelial Weibel-Palade bodies (WPB) and secreted upon cell
      stimulation to act in recruiting platelets to sites of vessel injury. Only fully
      matured multimeric vWF represents an efficient anchor for platelets, and
      endothelial cells have developed mechanisms to prevent release of immature vWF.
      Full maturation of vWF occurs within WPB following their translocation from a
      perinuclear site of emergence at the trans-Golgi network (TGN) to the cell
      periphery. The WPB-associated small GTPase Rab27a is involved in restricting
      immature WPB exocytosis and we searched for links between Rab27a and the actin
      cytoskeleton that could anchor WPB inside endothelial cells until they are fully
      matured. We here identify myosin Va as such link. Myosin Va forms a tripartite
      complex with Rab27a and its effector MyRIP and depletion of or dominant-negative
      interference with myosin Va leads to an increase in the ratio of perinuclear to
      more peripheral WPB. Concomitantly, myosin Va depletion results in an elevated
      secretion of less-oligomeric vWF from histamine-stimulated endothelial cells.
      These results indicate that a Rab27a/MyRIP/myosin Va complex is involved in
      linking WPB to the peripheral actin cytoskeleton of endothelial cells to allow
      full maturation and prevent premature secretion of vWF.

PMID- 21740492
TI  - Investigation into the acceptability of door locking to staff, patients, and
      visitors on acute psychiatric wards.
AB  - There is disagreement among psychiatric professionals about whether the doors of
      acute psychiatric wards should be kept locked to prevent patients from leaving
      and harming themselves or others. This study explored patient, staff, and visitor
      perceptions about the acceptability of locking the ward door on acute psychiatric
      inpatient wards. Interviews were conducted with 14 registered nurses, 15
      patients, and six visitors from three different acute wards. Findings revealed
      commonalities across all groups, with general agreement that locking the door
      reduced absconding. Staff expressed feelings of guilt, embarrassment, and fear of
      being blamed when a patient absconded. Staff also reported that open wards
      created anxious vigilance to prevent an abscond and increased workload in
      allocating staff to watch the door, whereas staff on partially-locked doors also
      perceived an increased workload in letting people in and out of the ward.
      Patients had mixed feelings about the status of the door, expressing depression,
      a sense of stigma, and low self-esteem when the door was locked. The issue of
      balancing safety and security on acute psychiatric wards against the autonomy of
      patients is not easily resolved, and requires focused research to develop
      innovative nursing practices.

PMID- 21740493
TI  - Critical role for NLRP3 in necrotic death triggered by Mycobacterium
      tuberculosis.
AB  - Induction of necrotic death in macrophages is a primary virulence determinant of
      Mycobacterium tuberculosis. The ESX-1 secretion system and its substrate ESAT-6
      are required for M. tuberculosis to induce necrosis, but host factors that
      mediate the ESAT-6-promoted necrosis remain unknown. Here we report that ESAT-6
      promoted necrotic death in THP-1 human macrophages is dependent on the NLRP3
      inflammasome, as shown by RNA interference and pharmacological inhibitions.
      Phagosomes containing ESAT-6-expressing M. tuberculosis recruit markers
      previously associated with damaged phagosomal membrane, such as galectin-3 and
      ubiquitinated protein aggregates. In addition, ESAT-6 promoted lysosomal
      permeabilization by M. tuberculosis. ESAT-6 mutants defective for ubiquitination
      were unable to trigger NLRP3 activation and necrotic death. Furthermore, Syk
      tyrosine kinase, recently implicated in NLRP3 activation during fungal and
      malarial infections, was necessary for mediating the ESAT-6-promoted necrosis and
      NLRP3 activation. Our results thus link phagosomal damage and Syk activity to
      NLRP3-mediated necrotic death triggered by M. tuberculosis ESAT-6 during
      infection.

PMID- 21740494
TI  - Dendritic cells in oral tolerance in the gut.
AB  - Oral tolerance is a process that allows generation of systemic unresponsiveness
      to food antigens. Hence if the same antigen is introduced systemically even under
      immunogenic conditions it does not induce immune responsiveness. Dendritic cells
      (DCs) have been identified as essential players in this process. DCs in the gut
      are located in a strategic position as they can interact directly with luminal
      antigens or indirectly after their transcytosis across epithelial cells. DCs can
      then migrate to associated lymphoid tissues to induce tolerance. Antigen
      presenting cells in the gut are specialized in function and have divided their
      labour so that there are cells capable to migrate to the draining mesenteric
      lymph node for induction of T regulatory cells, while other subsets are resident
      and are required to enforce tolerance locally in the gut after food antigen
      exposure. In this review, I shall summarize the characteristics of antigen
      presenting cells in the gut and their involvement in oral tolerance induction. In
      addition, I will also emphasize that tolerance to food allergens may be
      contributed by plasmacytoid DCs in the liver that participate to the elimination
      or anergy of allergen-specific CD8 T cells. Hence specialized functions are
      associated to different subsets of antigen presenting cells and different organs.

PMID- 21740495
TI  - Spiroplasma and host immunity: activation of humoral immune responses increases
      endosymbiont load and susceptibility to certain Gram-negative bacterial pathogens
      in Drosophila melanogaster.
AB  - Spiroplasma poulsonii and its relatives are facultative, vertically transmitted
      endosymbionts harboured by several Drosophila species. Their long-term survival
      requires not only evasion of host immunity, but also that Spiroplasma does not
      have a net detrimental effect on host fitness. These requirements provide the
      central framework for interactions between host and endosymbiont. We use
      Drosophila melaogaster as a model to unravel aspects of the mechanistic basis of
      endosymbiont-host immune interactions. Here we show that Spiroplasma does not
      activate an immune response in Drosophila and is not susceptible to either the
      cellular or humoral arms of the Drosophila immune system. We gain unexpected
      insight into host factors that can promote Spiroplasma growth by showing that
      activation of Toll and Imd immune pathways actually increases Sprioplasma titre.
      Spiroplasma-mediated protection is not observed for variety of fungal and
      bacterial pathogens and Spiroplasma actually increases susceptibility of
      Drosophila to certain Gram-negative pathogens. Finally, we show that the growth
      of endosymbiotic Spiroplasma is apparently self-regulated, as suggested by the
      unhindered proliferation of non-endosymbiotic Spiroplasma citri in fly
      haemolymph.

PMID- 21740496
TI  - Highly co-ordinated var gene expression and switching in clinical Plasmodium
      falciparum isolates from non-immune malaria patients.
AB  - Antigenic variation to fool the immune system is one of the molecular tricks
      Plasmodium uses to maintain infection in its human host. The exclusive expression
      of the surface-exposed PfEMP1 molecules, encoded by var genes, is the best
      example for this. Central questions regarding the dynamics of antigenic
      variation, namely the rate of switching and the regulation of var gene expression
      in Plasmodium falciparum, are yet unanswered. To elucidate the in vivo situation,
      we studied var gene switching by analysing the var transcripts from parasites
      isolated from 20 non-immune malaria patients as well as during subsequent in
      vitro generations. Parasites were found to be highly co-ordinated as the whole
      population isolated from individual patients usually expressed only one dominant 
      preferentially group A -var gene. While some isolates have very low switching
      rates, others switched their var gene expression in every generation. However,
      during extended cultivation the co-ordinated expression and switching is lost
      resulting in random expression of all var gene groups. Switching as observed on
      the RNA level was also supported on the protein level using PfEMP1-specific
      antibodies. The results suggest that var genes switch in an ordered, hierarchical
      manner at much higher rates than previously described.

PMID- 21740497
TI  - Ubiquitylation and autophagy in the control of bacterial infections and related
      inflammatory responses.
AB  - The ubiquitin proteasome system and autophagy constitute key signalling pathways
      in the host response to infection. The identification of adaptors linking the two
      pathways has prompted a re-examination of the latter's involvement in
      inflammatory reactions and the clearance of bacteria. The ubiquitin-autophagy
      pathway is a preferred target for effectors from pathogens that seek to exploit
      and evade the host defence mechanisms. A number of new players and signalling
      nodes have recently been identified. Here, we discuss these new insights into the
      host's control of bacterial infection.

PMID- 21740498
TI  - Infection with Leishmania amazonensis upregulates purinergic receptor expression
      and induces host-cell susceptibility to UTP-mediated apoptosis.
AB  - Nucleotides are released into the extracellular milieu from infected cells and
      cells at inflammatory sites. The extracellular nucleotides bind to specific
      purinergic (P2) receptors and thereby induce a variety of cellular responses
      including anti-parasitic effects. Here we investigated whether extracellular
      nucleotides affect leishmanial infection in macrophages, and found that UTP
      reduces strongly the parasite load in peritoneal macrophages. Ultrastructural
      analysis of infected cells revealed that UTP induced morphological damage in the
      intracellular parasites. Uridine nucleotides also induced dose-dependent
      apoptosis of macrophages and production of ROI and RNI only in infected
      macrophages. The intracellular calcium measurements of infected cells showed that
      the response to UTP, but not UDP, increased the sensitivity and amplitude of
      cytosolic Ca(2+) changes. Infection of macrophages with Leishmania upregulated
      the expression of P2Y(2) and P2Y(4) receptor mRNA. The data suggest indirectly
      that Leishmania amazonensis infection induces modulation and heteromerization of
      P2Y receptors on macrophages. Thus UTP modulates the host response against L.
      amazonensis infection. UTP and UTP homologues should therefore be considered as
      novel components of therapeutic strategies against cutaneous leishmaniasis.

PMID- 21740499
TI  - EspG of enteropathogenic and enterohemorrhagic E. coli binds the Golgi matrix
      protein GM130 and disrupts the Golgi structure and function.
AB  - The enteric pathogens enteropathogenic Escherichia coli (EPEC),
      enterohaemorrhagic E. coli (EHEC) and Shigella flexneri all translocate at least
      one effector protein of the EspG protein family into host cells via a type III
      secretion system (T3SS). The EspG family comprises EspG, EspG2 and VirA. From a
      Y2H screen, we identified the Golgi matrix protein GM130 as a potential binding
      partner of EspG. We confirmed EspG:GM130 protein interaction by affinity co
      purification. In co-immunoprecipitation experiments EspG was co-precipitated with
      GM130 while both GM130 and tubulins were co-precipitated with EspG. When
      expressed ectopically in HeLa cells, the EspG protein family all localized to the
      Golgi and induced fragmentation of the Golgi apparatus. All EspG family proteins
      were also able to disrupt protein secretion to a greater extent than the T3SS
      effector NleA/EspI, which has previously been shown to localize to the Golgi and
      interact with SEC24 to disrupt COPII vesicle formation. We hypothesize that
      EspG:GM130 interaction disrupts protein secretion either through direct
      disruption of GM130 function or through recruitment of other EspG interacting
      proteins to the Golgi.

PMID- 21740500
TI  - Eating the strangers within: host control of intracellular bacteria via
      xenophagy.
AB  - Many bacterial pathogens rely on an intracellular cycle to ensure their
      proliferation within infected hosts, through their ability to avoid or circumvent
      host bactericidal pathways. Recent evidence supports an increasingly important
      role for the autophagy pathway in innate immune defences against intracellular
      pathogens, as a mechanism of capture of either cytosol-adapted or vacuolar
      bacteria that redirect them to the lysosomal compartment for killing.
      Antibacterial autophagy, also referred to as xenophagy, involves selective
      recognition of intracellular bacteria and their targeting to the autophagic
      machinery for degradation. Here we review recent advances in our molecular
      understanding of these processes, and in how bacteria have adapted to avoid
      xenophagy or even take advantage of this innate immune process.

PMID- 21740501
TI  - The IL-23 axis in Salmonella gastroenteritis.
AB  - Non-typhoidal Salmonella (NTS) serotypes cause a localized gastroenteritis in
      immunocompetent individuals. In contrast, primary immunodeficiencies that impair
      interleukin-23 (IL-23)-dependent pathways are associated in humans with
      disseminated NTS bloodstream infections (bacteraemia). The recent use of animal
      models has helped to define the role the IL-23 axis plays during NTS
      gastroenteritis, but additional work is needed to elucidate how this host defence
      pathway prevents NTS bacteraemia.

PMID- 21740502
TI  - In young adults with a low body mass index ultrasonography is sufficient as a
      diagnostic tool for ureteric stones.
AB  - OBJECTIVE: * To identify additional factors that might improve the diagnosis of
      ureteric stones using ultrasonography (US) as the primary diagnostic method.
      PATIENTS AND METHODS: * We performed a retrospective study of 228 patients who
      underwent rigid ureterorenoscopy (URS) for obstructive ureteric stones. * Patient
      age, sex, body mass index (BMI) and stone location and size were recorded. * All
      patients underwent US for stone detection before surgery. * If no cause of the
      flank pain was found by US, computer tomography (CT) was performed to confirm the
      absence of ureteric stones. RESULTS: * In 57 (25%), 15 (6.6%) and 156 (68.4%)
      patients a stone was localized on the proximal, mid- and distal ureter,
      respectively. * In 96 (42.1%), 122 (53.5%) and 10 (4.4%) patients the stone
      measured 0-5, 6-10 and >10 mm, respectively. * The mean (range) BMI of the
      patients was 24.7 (17.3-37.2) kg/m(2). * The overall stone detection rate using
      US was 86.4% overall, and 96.4% in adults <= 35 years. In 72/197 patients (36.5%)
      the stones found using US measured <= 5 mm and in 24/31 patients (77.4%) the
      stones found using CT measured <= 5 mm. * Age (P= 0.008), stone size (P < 0.001)
      and BMI (P= 0.013) were factors that independently affected ureteric stone
      diagnosis using US. CONCLUSION: * Although CT has served as the 'gold standard'
      for stone detection, its high costs and radiation dose, together with the high
      detection rate of US in the hands of experienced radiologists, lead us to
      conclude that US should be the first choice for primary diagnostic purposes,
      especially in young slim adults as no patient <= 35 years with a BMI <= 24
      kg/m(2) needed unenhanced CT for ureteric stone diagnosis.

PMID- 21740503
TI  - Evolutionary causes and consequences of sequential polyandry in anuran
      amphibians.
AB  - Among anuran amphibians (frogs and toads), there are two types of polyandry:
      simultaneous polyandry, where sperm from multiple males compete to fertilize
      eggs, and sequential polyandry, where eggs from a single female are fertilized by
      multiple males in a series of temporally separate mating events, and sperm
      competition is absent. Here we review the occurrence of sequential polyandry in
      anuran amphibians, outline theoretical explanations for the evolution of this
      mating system and discuss potential evolutionary implications. Sequential
      polyandry has been reported in a limited number of anurans, but its widespread
      taxonomic and geographic distribution suggests it may be common. There have been
      no empirical studies that have explicitly investigated the evolutionary
      consequences of sequential polyandry in anurans, but species with this mating
      pattern share an array of behavioural, morphological and physiological
      characteristics, suggesting that there has been common sexual selection on their
      reproductive system. Sequential polyandry may have a number of adaptive benefits,
      including spreading the risk of brood failure in unpredictable environments,
      insuring against male infertility, or providing genetic benefits, either through
      good genes, intrinsic compatibility or genetic diversity effects. Anurans with
      sequential polyandry provide untapped opportunities for innovative research
      approaches that will contribute significantly to understanding anuran evolution
      and also, more broadly, to the development of sexual-selection and life-history
      theory.

PMID- 21740504
TI  - Recombinant plant-expressed tumour-associated MUC1 peptide is immunogenic and
      capable of breaking tolerance in MUC1.Tg mice.
AB  - The human epithelial mucin MUC1 is a heavily glycosylated transmembrane protein
      that is overexpressed and aberrantly glycosylated on over 90% of human breast
      cancers. The altered glycosylation of MUC1 reveals an immunodominant peptide
      along its tandem repeat (TR) that has been used as a target for tumour
      immunotherapy. In this study, we used the MUC1 TR peptide as a test antigen to
      determine whether a plant-expressed human tumour-associated antigen can be
      successfully expressed in a plant system and whether it will be able to break
      self-antigen tolerance in a MUC1-tolerant mouse model. We report the expression
      of MUC1 TR peptide fused to the mucosal-targeting Escherichia coli enterotoxin B
      subunit (LTB-MUC1) in a plant host. Utilizing a rapid viral replicon transient
      expression system, we obtained high yields of LTB-MUC1. Importantly, the LTB-MUC1
      fusion protein displayed post-translational modifications that affected its
      antigenicity. Glycan analysis revealed that LTB-MUC1 was glycosylated and a MUC1
      specific monoclonal antibody detected only the glycosylated forms. A thorough
      saccharide analysis revealed that the glycans are tri-arabinans linked to
      hydroxyprolines within the MUC1 tandem repeat sequence. We immunized MUC1
      tolerant mice (MUC1.Tg) with transiently expressed LTB-MUC1, and observed
      production of anti-MUC1 serum antibodies, indicating breach of tolerance. The
      results indicate that a plant-derived human tumour-associated antigen is
      equivalent to the human antigen in the context of immune recognition.

PMID- 21740506
TI  - Comparative anatomy of embryogenesis in three species of Podostemaceae and
      evolution of the loss of embryonic shoot and root meristems.
AB  - During embryogenesis in angiosperms, the embryonic shoot and root meristems are
      created at opposite poles of the embryo, establishing a vertical body plan.
      However, the aquatic eudicot family Podostemaceae exhibits an unusual horizontal
      body plan, which is attributed to the loss of embryonic shoot and root meristems.
      To infer the embryogenetic changes responsible for the loss of these meristems,
      we examined the embryogenesis of three podostemads with different meristem
      characters, that is, Terniopsis brevis with distinct shoot and root meristems,
      Zeylanidium lichenoides with reduced shoot and no root meristems, and Hydrobryum
      japonicum with no shoot and no root meristems. In T. brevis, as in other
      eudicots, the putative organizing center (OC) and L1 layer (=the epidermal cell
      layer) arose to generate a distinct shoot meristem initial, and the hypophysis
      formed the putative quiescent center (QC) of a root meristem. Z. lichenoides had
      a morphologically unrecognizable shoot meristem, because a distinct L1 layer did
      not develop, whereas the putative OC precursor arose normally. In H. japonicum,
      the vertical divisions of the apical cells of eight-cell embryo prevented
      putative OC initiation. In Z. lichenoides and H. japonicum, the putative QC
      failed to initiate because the hypophysis repeated longitudinal divisions during
      early embryogenesis. Based on their phylogenetic relationships, we infer that the
      conventional embryonic shoot meristem was lost in Podostemaceae via two steps,
      that is, the loss of a distinct L1 layer and the loss of the OC, whereas the loss
      of the embryonic root meristem occurred once by misspecification of the
      hypophysis.

PMID- 21740507
TI  - Evolution of the Alx homeobox gene family: parallel retention and independent
      loss of the vertebrate Alx3 gene.
AB  - The Alx gene family is implicated in craniofacial development and comprises two
      to four homeobox genes in each vertebrate genome analyzed. Using phylogenetics
      and comparative genomics, we show that the common ancestor of jawed vertebrates
      had three Alx genes descendent from the two-round genome duplications (Alx1,
      Alx3, Alx4), compared with a single amphioxus gene. Later in evolution one of the
      paralogues, Alx3, was lost independently from at least three different vertebrate
      lineages, whereas Alx1 and Alx4 were consistently retained. Comparison of spatial
      gene expression patterns reveals that the three mouse genes have equivalent
      craniofacial expression to the two chick and frog genes, suggesting that
      redundancy compensated for gene loss. We suggest that multiple independent loss
      of one Alx gene was predisposed by extensive and persistent overlap in gene
      expression between Alx paralogues. Even so, it is unclear whether it was
      coincidence or evolutionary bias that resulted in the same Alx gene being lost on
      each occasion, rather than different members of the gene family.

PMID- 21740508
TI  - Gonad development in Midas cichlids and the evolution of sex change in fishes.
AB  - Some fishes mature and function as one sex and later transform to the other sex
      in response to social interactions. Previous evidence suggested that a change in
      developmental timing may be involved in the evolution of adult sex change in
      fishes. The most recent support for this idea came from reports that sex in the
      Midas cichlid, Amphilophus citrinellus, was determined by social conditions
      experienced at the juvenile stage. Differentiation as a male was reported to be
      dependent on large body size relative to group-mates, and thought to be mediated
      through aggressive interactions. Here I demonstrate that socially controlled sex
      determination does not occur as was originally reported. Previously, I found that
      sex was not associated with body size in juveniles either in nature or in
      captivity. Similarly, I found no association between aggressive behavior and sex
      in juveniles. I later demonstrated that socially controlled sex determination
      does not typically occur in the Midas cichlid and closely related species and
      supported an alternative mechanism to explain large body size in adult males.
      Finally, in the current study I analyze gonad histology of fish from the same
      population used by the original authors and lay to rest the idea of socially
      controlled sex determination in this species. Recent observations of socially
      controlled sex determination in juveniles of species that typically change sex at
      the adult stage are examples of phenotypic plasticity, not genetic variation.
      Therefore, juvenile socially controlled sex determination does not support a
      theory that a change in developmental timing is involved in the evolution of
      adult sex change in fishes.

PMID- 21740509
TI  - Evolutionary and developmental dynamics of the dentition in Muroidea and
      Dipodoidea (Rodentia, Mammalia).
AB  - When it comes to mouse evo-devo, the fourth premolar-first molar (P4-M1) dental
      complex becomes a source of longstanding controversies among paleontologists and
      biologists. Muroidea possess only molar teeth but with additional mesial cusps on
      their M1. Developmental studies tend to demonstrate that the formation of such
      mesial cusps could result from the integration of a P4 germ into M1 during
      odontogenesis. Conversely, most Dipodoidea conserve their fourth upper premolars
      and those that lost these teeth can also bear additional mesial cusps on their
      first upper molars. The aim of this study is to assess this developmental model
      in both Muroidea and Dipodoidea by documenting the morphological evolution of the
      P4-M1 complex across 50 Ma. Fourteen extinct and extant species, including
      abnormal and mutant specimens were investigated. We found that, even if their
      dental evolutionary pathways strongly differ, Dipodoidea and Muroidea retain
      common developmental characteristics because some of them can present similar
      dental morphological trends. It also appears that the acquisition of a mesial
      cusp on M1 is independent from the loss of P4 in both superfamilies. Actually,
      the progressive decrease of the inhibitory effect of P4, consequent to its
      regression, could allow the M1 to lengthen and mesial cusps to grow in Muroidea.
      Apart from these developmental explanations, patternings of the mesial part of
      first molars are also deeply constrained by morpho-functional requirements. As
      there is no obvious evidence of such mechanisms in Dipodoidea given their more
      variable dental morphologies, further developmental investigations are needed.

PMID- 21740510
TI  - Coelomogenesis during the abbreviated development of the echinoid Heliocidaris
      erythrogramma and the developmental origin of the echinoderm pentameral body
      plan.
AB  - The development of the coeloms is described in an echinoid with an abbreviated
      larval development and shows the early morphogenesis of the coeloms of the adult
      stage. The development is described from images obtained by laser scanning
      confocal microscopy. The development in Heliocidaris erythrogramma is asymmetric
      with a larger left coelom forming on the larval-left side and a smaller right
      coelom forming on the larval-right side. The right coelom forms after the
      development of the left coelom is well advanced. The hydrocoele forms from the
      anterior part of the left coelom. The five lobes of the hydrocoele from which the
      pentamery of the adult derives take shape on the outer, distal wall of the
      anterior part of the left coelom. The hydrocoele separates from the more
      posterior part of the left coelom, which becomes the left posterior coelom. The
      lobes of the hydrocoele are named, based on the site of the connexion of the
      stone canal to the hydrocoele. The mouth is assumed to form by penetration
      through only the outer, distal wall of the hydrocoele and the ectoderm. Both
      larval and adult polarities are evident in this larva. A comparison with
      coelomogenesis in the asteroid Parvulastra exigua, which also has an abbreviated
      development, leads to predictions of homology between the echinoderm and chordate
      phyla that do not require the hypothesis of a dorsoventral inversion event in
      chordates.

PMID- 21740511
TI  - Revealing the mechanisms of the rostral shift of pelvic fins among teleost
      fishes.
AB  - In teleost fishes, the position of the pelvic fins shift during evolution; this
      positional shift seems to have diversified their locomotion and feeding behavior,
      thereby expanding the habitats of these fishes. Thus, such a positional shift of
      the pelvic fins is one of the significant features of teleost fishes from
      evolutionary, embryological, and taxonomic viewpoints, but no studies to date
      have investigated the mechanism for the rostral shift of the pelvic fins from the
      anal region in teleosts. Examining the fate of the prospective pelvic fin cells
      of the zebrafish Danio rerio and the Nile tilapia Oreochromis niloticus embryos
      demonstrates that the prospective pelvic fin cells are originally located near
      the anus, as seen in tetrapods, but their position shifts with respect to the
      body trunk after its protrusion from the yolk surface. In this article, we
      highlight such recent findings and discuss the mechanisms of pelvic fin evolution
      among teleost fishes.

PMID- 21740512
TI  - Emerging model systems in eco-evo-devo: the environmentally responsive spadefoot
      toad.
AB  - Spadefoot toads have emerged as a model system for addressing fundamental
      questions in ecological and evolutionary developmental biology (eco-evo-devo).
      Their tadpoles produce a wide range of adaptive phenotypes in direct response to
      diverse environmental stimuli. Such phenotypic plasticity offers an excellent
      opportunity to examine how an organism's ecology affects its development as well
      as how an organism's development influences its ecology and evolution. By
      characterizing and understanding the interconnectedness between an organism's
      environment, its development responses, and its ecological interactions in
      natural populations, such research promises to clarify further the role of the
      environment in not only selecting among diverse phenotypes, but also creating
      such phenotypes in the first place.

PMID- 21740517
TI  - Prospective clinical study evaluating the long-time adjunctive use of
      chlorhexidine after one-stage full-mouth SRP.

PMID- 21740513
TI  - Lucifer yellow - an angel rather than the devil.
AB  - The fluorescent dye Lucifer yellow (LY) was introduced in 1978, and has been
      extremely useful in studying cell structure and communications. This dye has been
      used mostly for labelling cells by intracellular injection from microelectrodes.
      This review describes the numerous applications of LY, with emphasis on the
      enteric nervous system and interstitial cells of Cajal. Of particular importance
      is the dye coupling method, which enables the detection of cell coupling by gap
      junctions.

PMID- 21740518
TI  - Ggamma recruitment system incorporating a novel signal amplification circuit to
      screen transient protein-protein interactions.
AB  - Weak and transient protein-protein interactions are associated with biological
      processes, but many are still undefined because of the difficulties in their
      identification. Here, we describe a redesigned method to screen transient protein
      protein interactions by using a novel signal amplification circuit, which is
      incorporated into yeast to artificially magnify the signal responding to the
      interactions. This refined method is based on the previously established Ggamma
      recruitment system, which utilizes yeast G-protein signaling and mating growth
      selection to screen interacting protein pairs. In the current study, to test the
      capability of our method, we chose mutants of the Z-domain derived from
      Staphylococcus aureus protein A as candidate proteins, and the Fc region of human
      IgG as the counterpart. By introduction of an artificial signal amplifier into
      the previous Ggamma recruitment system, the signal transduction responding to
      transient interactions between Z-domain mutants and the Fc region with
      significantly low affinity (8.0 * 10(3) M(-1)) was successfully amplified in
      recombinant haploid yeast cells. As a result of zygosis with the opposite mating
      type of wild-type haploid cells, diploid colonies were vigorously and selectively
      generated on the screening plates, whereas our previous system rarely produced
      positive colonies. This new approach will be useful for exploring the numerous
      transient interactions that remain undefined because of the lack of powerful
      screening tools for their identification.

PMID- 21740519
TI  - Cyclic ADP-ribose requires CD38 to regulate the release of ATP in visceral smooth
      muscle.
AB  - It is well established that the intracellular second messenger cADP-ribose
      (cADPR) activates Ca(2+) release from the sarcoplasmic reticulum through
      ryanodine receptors. CD38 is a multifunctional enzyme involved in the formation
      of cADPR in mammals. CD38 has also been reported to transport cADPR in several
      cell lines. Here, we demonstrate a role for extracellular cADPR and CD38 in
      modulating the spontaneous, but not the electrical field stimulation-evoked,
      release of ATP in visceral smooth muscle. Using a small-volume superfusion assay
      and an HPLC technique with fluorescence detection, we measured the spontaneous
      and evoked release of ATP in bladder detrusor smooth muscles isolated from
      CD38(+/+) and CD38(-/-) mice. cADPR (1 nM) enhanced the spontaneous overflow of
      ATP in bladders isolated from CD38(+/+) mice. This effect was abolished by the
      inhibitor of cADPR receptors on sarcoplasmic reticulum 8-bromo-cADPR (80 MUM) and
      by ryanodine (50 MUm), but not by the nonselective P2 purinergic receptor
      antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonate (30 MUM). cADPR
      failed to facilitate the spontaneous ATP overflow in bladders isolated from CD38(
      /-) mice, indicating that CD38 is crucial for the enhancing effects of
      extracellular cADPR on spontaneous ATP release. Contractile responses to ATP were
      potentiated by cADPR, suggesting that the two adenine nucleotides may work in
      synergy to maintain the resting tone of the bladder. In conclusion, extracellular
      cADPR enhances the spontaneous release of ATP in the bladder by influx via CD38
      and subsequent activation of intracellular cADPR receptors, probably causing an
      increase in intracellular Ca(2+) in neuronal cells.

PMID- 21740520
TI  - The ABC of ABCs: multidrug resistance and genetic diseases.

PMID- 21740522
TI  - The N-terminal region of the bacterial DNA polymerase PolC features a pair of
      domains, both distantly related to domain V of the DNA polymerase III tau
      subunit.
AB  - PolC is one of two essential replicative DNA polymerases in Bacillus subtilis and
      other Gram-positive bacteria. The 3D structure of PolC has recently been solved,
      yet it lacks the N-terminal region. For this PolC region of ~ 230 residues, both
      the structure and function are unknown. In the present study, using sensitive
      homology detection and comparative protein structure modeling, we identified, in
      this enigmatic region, two consecutive globular domains, PolC-NI and PolC-NII,
      which are followed by an apparently unstructured linker. Unexpectedly, we found
      that both domains are related to domain V of the tau subunit, which is part of
      the bacterial DNA polymerase III holoenzyme. Despite their common homology to
      tau, PolC-NI and PolC-NII exhibit very little sequence similarity to each other.
      This observation argues against simple tandem duplication within PolC as the
      origin of the two-domain structure. Using the derived structural models, we
      analyzed residue conservation and the surface properties of both PolC N-terminal
      domains. We detected a surface patch of positive electrostatic potential in PolC
      NI and a hydrophobic surface patch in PolC-NII, suggesting their possible
      involvement in nucleic acid and protein binding, respectively. PolC is known to
      interact with the tau subunit, however, the region responsible for this
      interaction is unknown. We propose that the PolC N-terminus is involved in
      mediating the PolC-tau interaction and possibly also in binding DNA.

PMID- 21740523
TI  - The ins and outs of pertussis toxin.
AB  - Pertussis toxin, produced and secreted by the whooping cough agent Bordetella
      pertussis, is one of the most complex soluble bacterial proteins. It is actively
      secreted through the B. pertussis cell envelope by the Ptl secretion system, a
      member of the widespread type IV secretion systems. The toxin is composed of five
      subunits (named S1 to S5 according to their decreasing molecular weights)
      arranged in an A-B structure. The A protomer is composed of the enzymatically
      active S1 subunit, which catalyzes ADP-ribosylation of the alpha subunit of
      trimeric G proteins, thereby disturbing the metabolic functions of the target
      cells, leading to a variety of biological activities. The B oligomer is composed
      of 1S2:1S3:2S4:1S5 and is responsible for binding of the toxin to the target cell
      receptors and for intracellular trafficking via receptor-mediated endocytosis and
      retrograde transport. The toxin is one of the most important virulence factors of
      B. pertussis and is a component of all current vaccines against whooping cough.

PMID- 21740521
TI  - Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic
      diseases.
AB  - The ATP-binding cassette (ABC) transporters are a superfamily of membrane
      proteins that are best known for their ability to transport a wide variety of
      exogenous and endogenous substances across membranes against a concentration
      gradient via ATP hydrolysis. There are seven subfamilies of human ABC
      transporters, one of the largest being the 'C' subfamily (gene symbol ABCC). Nine
      ABCC subfamily members, the so-called multidrug resistance proteins (MRPs) 1-9,
      have been implicated in mediating multidrug resistance in tumor cells to varying
      degrees as the efflux extrude chemotherapeutic compounds (or their metabolites)
      from malignant cells. Some of the MRPs are also known to either influence drug
      disposition in normal tissues or modulate the elimination of drugs (or their
      metabolites) via hepatobiliary or renal excretory pathways. In addition, the
      cellular efflux of physiologically important organic anions such as leukotriene
      C(4) and cAMP is mediated by one or more of the MRPs. Finally, mutations in
      several MRPs are associated with human genetic disorders. In this minireview, the
      current biochemical and physiological knowledge of MRP1-MRP9 in cancer
      chemotherapy and human genetic disease is summarized. The mutations in MRP2/ABCC2
      leading to conjugated hyperbilirubinemia (Dubin-Johnson syndrome) and in
      MRP6/ABCC6 leading to the connective tissue disorder Pseudoxanthoma elasticum are
      also discussed.

PMID- 21740524
TI  - Deficiency in apolipoprotein E has a protective effect on diet-induced
      nonalcoholic fatty liver disease in mice.
AB  - Apolipoprotein E (apoE) mediates the efficient catabolism of the chylomicron
      remnants very low-density lipoprotein and low-density lipoprotein from the
      circulation, and the de novo biogenesis of high-density lipoprotein. Lipid-bound
      apoE is the natural ligand for the low-density lipoprotein receptor (LDLr), LDLr
      related protein 1 and other scavenger receptors. Recently, we have established
      that deficiency in apoE renders mice resistant to diet-induced obesity. In the
      light of these well-documented properties of apoE, we sought to investigate its
      role in the development of diet-induced nonalcoholic fatty liver disease (NAFLD).
      apoE-deficient, LDLr-deficient and control C57BL/6 mice were fed a western-type
      diet (17.3% protein, 48.5% carbohydrate, 21.2% fat, 0.2% cholesterol, 4.5 kcal.g(
      )) for 24 weeks and their sensitivity to NAFLD was assessed by histological and
      biochemical methods. apoE-deficient mice were less sensitive than control C57BL/6
      mice to diet-induced NAFLD. In an attempt to identify the molecular basis for
      this phenomenon, biochemical and kinetic analyses revealed that apoE-deficient
      mice displayed a significantly delayed post-prandial triglyceride clearance from
      their plasma. In contrast with apoE-deficient mice, LDLr-deficient mice fed a
      western-type diet for 24 weeks developed significant accumulation of hepatic
      triglycerides and NAFLD, suggesting that apoE-mediated hepatic triglyceride
      accumulation in mice is independent of LDLr. Our findings suggest a new role of
      apoE as a key peripheral contributor to hepatic lipid homeostasis and the
      development of diet-induced NAFLD.

PMID- 21740525
TI  - Carboxylate and aromatic active-site residues are determinants of high-affinity
      binding of omega-aminoaldehydes to plant aminoaldehyde dehydrogenases.
AB  - The crystal structures of both isoforms of the aminoaldehyde dehydrogenase from
      pea (PsAMADH) have been solved recently [Tylichovaet al. (2010) J Mol Biol396,
      870-882]. The characterization of the PsAMADH2 proteins, altered here by site
      directed mutagenesis, suggests that the D110 and D113 residues at the entrance to
      the substrate channel are required for high-affinity binding of omega
      aminoaldehydes to PsAMADH2 and for enzyme activity, whereas N162, near catalytic
      C294, contributes mainly to the enzyme's catalytic rate. Inside the substrate
      cavity, W170 and Y163, and, to a certain extent, L166 and M167 probably preserve
      the optimal overall geometry of the substrate channel that allows for the
      appropriate orientation of the substrate. Unconserved W288 appears to affect the
      affinity of the enzyme for the substrate amino group through control of the
      substrate channel diameter without affecting the reaction rate. Therefore, W288
      may be a key determinant of the differences in substrate specificity found among
      plant AMADH isoforms when they interact with naturally occurring substrates such
      as 3-aminopropionaldehyde and 4-aminobutyraldehyde.

PMID- 21740526
TI  - The predictive value of epidermal growth factor receptor expression for
      sensitivity to vinorelbine in breast cancer.
AB  - Breast cancer patients with positive epidermal growth factor receptor (EGFR)
      expression have significantly worse post-relapse prognosis than patients with
      negative EGFR expression. Vinorelbine (NVB) is usually reserved as a salvage
      therapy after anthracyclines and taxanes in patients with breast cancer. To see
      whether EGFR expression has a predictive value in NVB-mediated effect on human
      breast cancer cells, we examined 50 primary breast cancer samples. Of these, 42%
      were found to be NVB sensitive by ATP-tumour chemosensitivity assay. Sensitivity
      was correlated with EGFR expression level (p = 0.001). To dynamically examine
      EGFR's effect on NVB sensitivity in breast cancer cells, we used the real-time
      cell electronic sensing system with EGFR-positive and EGFR-negative breast cancer
      cell lines, MCF-7 and MDA-MB-435s, respectively. MCF-7 is NVB sensitive, while
      MDA-MB-435 is NVB resistant. NVB-induced cytotoxicity to MCF-7 can be partly
      reversed with inhibitory anti-EGFR antibody. NVB up-regulated EGFR expression in
      MCF-7 cells, which affects ERK1/2 phosphorylation. This cellular response
      mechanism may cause greater input to non-lethally damaged cells. These data
      suggest that EGFR expression can be used as a prognostic factor for breast cancer
      sensitivity to NVB, which could help identify appropriate treatments for breast
      cancer.

PMID- 21740527
TI  - Immune modulation of resistance artery remodelling.
AB  - Low-grade inflammation plays a role in cardiovascular disease. The innate and the
      adaptive immune responses participate in mechanisms that contribute to
      inflammatory responses. It has been increasingly appreciated that different
      subsets of lymphocytes and the cytokines they produce modulate the vascular
      remodelling that occurs in cardiovascular disease. Effector T cells such as T
      helper (Th) 1 (interferon-gamma-producing) and Th2 lymphocytes (that produce
      interleukin-4), as well as Th17 (that produce interleukin-17), and T suppressor
      lymphocytes including regulatory T cells (Treg), which express the transcription
      factor forkhead box P3 (Foxp3), are involved in the remodelling of small arteries
      that occurs under the action of angiotensin II, deoxycorticosterone-salt and
      aldosterone-salt, as well as in models of hypertension such as the Dahl-salt
      sensitive rat. The mechanism whereby the immune system is activated is unclear,
      but it has been suggested that neo-antigens may be generated by the elevation of
      blood pressure or other stimuli, leading to the activation of the immune
      response. Activated Th1 may contribute to vascular remodelling directly on blood
      vessels via effects of the cytokines produced or indirectly by actions on the
      kidney. The protective effect of Treg may be mediated similarly directly or via
      renal effects. These data offer promise for the discovery of new therapeutic
      targets to ameliorate vascular remodelling, which could lead to improved outcome
      in cardiovascular disease in humans.

PMID- 21740528
TI  - Foetal exposure to food and environmental carcinogens in human beings.
AB  - Exposure to many different chemicals during pregnancy through maternal
      circulation is possible. Transplacental transfer of xenobiotics can be
      demonstrated using human placental perfusion. Also, placental perfusion can give
      information about the placental kinetics as well as metabolism and accumulation
      in the placenta because it retains the tissue structure and function. Although
      human placental perfusion has been used extensively to study the transplacental
      transfer of drugs, the information on food and environmental carcinogens is much
      more limited. This review deals with the foetal exposure to food and
      environmental carcinogens in human beings. In particular, human transplacental
      transfer of the food carcinogens such as acrylamide, glycidamide and
      nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the
      functional capacity of human placenta to induce DNA adduct formation or
      metabolize these above mentioned CYP2E1 substrates is of interest in this
      context. 

PMID- 21740529
TI  - The dopamine receptors mediating inhibition of the sympathetic vasopressor
      outflow in pithed rats: pharmacological correlation with the D(2) -like type.
AB  - This study investigated in pithed rats whether dopamine can inhibit the
      sympathetic vasopressor outflow and analysed the pharmacological profile of the
      receptors involved. Male Wistar pithed rats were pre-treated with intravenous
      (i.v.) bolus injections of gallamine (25 mg/kg) and desipramine (50 MUg/kg). The
      vasopressor responses to electrical stimulation of the sympathetic vasopressor
      outflow (0.03-3 Hz; 50 V and 2 msec.) were analysed before and during i.v.
      continuous infusions of the agonists dopamine (endogenous ligand), SKF-38393
      (D(1) -like) or quinpirole (D(2) -like). If inhibition was produced by any
      agonist, then its capability to inhibit the vasopressor responses to i.v. bolus
      injections of exogenous noradrenaline (0.03-3 MUg/kg) was also investigated.
      Dopamine (3-100 MUg/kg min.) inhibited the vasopressor responses to both
      electrical stimulation and noradrenaline. In contrast, SKF-38393 (10-100 MUg/kg
      min.) failed to inhibit the vasopressor responses to electrical stimulation;
      whereas quinpirole (0.1-30 MUg/kg min.) inhibited the vasopressor responses to
      electrical stimulation but not those to noradrenaline. The sympatho-inhibition by
      quinpirole (1 MUg/kg min.) remained unaltered after i.v. SCH 23390 (300 and 1000
      MUg/kg; D(1) -like receptor antagonist), but was abolished after i.v. raclopride
      (1000 MUg/kg; D(2) -like receptor antagonist). These doses of antagonists did not
      modify per se the sympathetically-induced vasopressor responses. In conclusion,
      quinpirole-induced inhibition of the sympathetic vasopressor outflow is primarily
      mediated by activation of dopamine D(2) -like receptors.

PMID- 21740531
TI  - Coumarin-based bioactive compounds: facile synthesis and biological evaluation of
      coumarin-fused 1,4-thiazepines.
AB  - As part of our ongoing studies on the synthesis of bioactive coumarin compounds,
      we synthesized a series of new coumarin-fused 1,4-thiazepines using a simple
      method. The biological activity of target compounds along with 3-(2
      hydroxybenzylidene)chroman-2,4-dione intermediates was screened by evaluation of
      their antioxidant and cytotoxic activities. The antioxidant activity was assessed
      using two methods, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging method and ferric reducing antioxidant power (FRAP) assay. 4
      Methoxyphenolic compound 5d in thiazepine series showed the most potent
      scavenging activity, while the 4-bromophenolic derivative 5b was the most
      efficient compound in FRAP assay. Also, the result of cytotoxic evaluation using
      MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay
      demonstrated that compound 5b is at least twofold more potent than etoposide
      against MCF-7, SK-N-MC, and MDA-MB 231 cell lines.

PMID- 21740530
TI  - Effects of slow, sustained, and rate-tunable nitric oxide donors on human aortic
      smooth muscle cells proliferation.
AB  - Smooth muscle cell (SMC) proliferation has been accepted as a common event in the
      pathophysiology of vascular diseases, including atherogenesis and intimal
      hyperplasia. Delivery of the nitric oxide synthase (NOS) substrate l-arginine,
      pharmacological nitric oxide (NO) donors, NO gas or overexpression of NOS
      proteins can inhibit SMC proliferation and reduce the injury responses within the
      blood vessel wall. Although commercial development of NO donors that attempt to
      provide exogenous delivery of NO has accelerated over the last few years, none of
      the currently available products can provide controlled, sustained, time-tunable
      release of NO. Nitrosamine-based NO donors, prepared in our laboratory, present a
      unique and innovative alternative for possible treatments for long-term NO
      deficiency-related diseases, including atherosclerosis, asthma, erectile
      dysfunction, cancer, and neurodegenerative diseases. A family of secondary amines
      prepared via nucleophilic aromatic displacement reactions could be readily N
      nitrosated to produce NO donors. NO release takes place in three distinct phases.
      During the initial phase, the release rate is extremely fast. In the second
      phase, the release is slower and the rate remains essentially the same during the
      final stage. These compounds inhibited up to 35% human aortic smooth muscle cell
      proliferation in a concentration-dependent manner.

PMID- 21740532
TI  - Omalizumab in patients with severe asthma: the XCLUSIVE study.
AB  - BACKGROUND AND AIMS: Although the efficacy and safety of omalizumab (OMA) in
      uncontrolled severe allergic asthma has been demonstrated in several randomised
      controlled trials (RCTs), information on the treatment in a practice-related
      setting is limited. Thus, the purpose of this prospective multi-centre study
      (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA
      therapy in real-life clinical practice in Germany. METHODS: One hundred ninety
      five asthmatic patients initiated on anti-Immunoglobulin E (IgE) IgE treatment
      were followed-up for 6 months. Forced expiratory volume in 1 s (FEV(1) ),
      exacerbation rate, days of absence, asthma symptoms [Asthma Control Questionnaire
      (ACQ)], a Global Evaluation of Treatment Effectiveness (GETE) and medication use
      were assessed. RESULTS: Measured outcome variables improved after a 16-week
      treatment period with OMA (FEV(1) +13.7% predicted P < 0.05, exacerbation rate 
      74.9% P < 0.0001, days of absence -92.1% P < 0.001, ACQ -43.7% P < 0.0001).
      Investigators evaluated the effectiveness of OMA by GETE in 78.8% as excellent or
      good (responder), and in 12.6%/8.6% as moderate/poor or worse (non-responder).
      Responders demonstrated better improvement of FEV(1), exacerbation rate, days of
      absence, ACQ and reduction of oral corticosteroids compared with non-responders.
      CONCLUSION: Results of effectiveness strongly suggest that the efficacy
      demonstrated in RCTs can be transposed to a clinical practice-related setting.

PMID- 21740534
TI  - Subcutaneous dirofilariosis in South-East Serbia--case report.
AB  - Human dirofilariosis is a relatively rare infection caused by filarial worms of
      the genus Dirofilaria. We herein report the first case of human subcutaneous
      dirofilariosis in the southeastern part of Serbia. A complete alive nematode was
      removed from a nodule in the periorbital region of a 50-year-old woman. The
      nematode was morphologically identified as a D. repens-like immature female. The
      diagnosis was confirmed with molecular methods. The patient was probably infected
      in the South-East Serbia as she had not travelled abroad, nor in other parts of
      Serbia such as Vojvodina, recently identified as a hyperendemic area for D.
      repens infection of dogs.

PMID- 21740535
TI  - Amorphous calcium phosphate and its application in dentistry.
AB  - Amorphous Calcium Phosphate (ACP) is an essential mineral phase formed in
      mineralized tissues and the first commercial product as artificial
      hydroxyapatite. ACP is unique among all forms of calcium phosphates in that it
      lacks long-range, periodic atomic scale order of crystalline calcium phosphates.
      The X-ray diffraction pattern is broad and diffuse with a maximum at 25 degree 2
      theta, and no other different features compared with well-crystallized
      hydroxyapatite. Under electron microscopy, its morphological form is shown as
      small spheroidal particles in the scale of tenths nanometer. In aqueous media,
      ACP is easily transformed into crystalline phases such as octacalcium phosphate
      and apatite due to the growing of microcrystalline. It has been demonstrated that
      ACP has better osteoconductivity and biodegradability than tricalcium phosphate
      and hydroxyapatite in vivo. Moreover, it can increase alkaline phosphatase
      activities of mesoblasts, enhance cell proliferation and promote cell adhesion.
      The unique role of ACP during the formation of mineralized tissues makes it a
      promising candidate material for tissue repair and regeneration. ACP may also be
      a potential remineralizing agent in dental applications. Recently developed ACP
      filled bioactive composites are believed to be effective anti
      demineralizing/remineralizing agents for the preservation and repair of tooth
      structures. This review provides an overview of the development, structure,
      chemical composition, morphological characterization, phase transformation and
      biomedical application of ACP in dentistry.

PMID- 21740536
TI  - Usefulness of primary care electronic networks to assess the incidence of
      chlamydia, diagnosed by general practitioners.
AB  - BACKGROUND: Chlamydia is the most common curable sexually transmitted infection
      (STI) in the Netherlands. The majority of chlamydia diagnoses are made by general
      practitioners (GPs). Baseline data from primary care will facilitate the future
      evaluation of the ongoing large population-based screening in the Netherlands.
      The aim of this study was to assess the usefulness of electronic medical records
      for monitoring the incidence of chlamydia cases diagnosed in primary care in the
      Netherlands. METHODS: In the electronic records of two regional and two national
      networks, we identified chlamydia diagnoses by means of ICPC codes (International
      Classification of Primary Care), laboratory results in free text and the
      prescription of antibiotics. The year of study was 2007 for the two regional
      networks and one national network, for the other national network the year of
      study was 2005. We calculated the incidence of diagnosed chlamydia cases per sex,
      age group and degree of urbanization. RESULTS: A large diversity was observed in
      the way chlamydia episodes were coded in the four different GP networks and how
      easily information concerning chlamydia diagnoses could be extracted. The overall
      incidence ranged from 103.2/100,000 to 590.2/100,000. Differences were partly
      related to differences between patient populations. Nevertheless, we observed
      similar trends in the incidence of chlamydia diagnoses in all networks and
      findings were in line with earlier reports. CONCLUSIONS: Electronic patient
      records, originally intended for individual patient care in general practice, can
      be an additional source of data for monitoring chlamydia incidence in primary
      care and can be of use in assessing the future impact of population-based
      chlamydia screening programs. To increase the usefulness of data we recommend
      more efforts to standardize registration by (specific) ICPC code and laboratory
      results across the existing GP networks.

PMID- 21740537
TI  - The ongoing dissection of the genetic architecture of autistic spectrum disorder.
AB  - The development of robust, non-hypothesis based case/control studies has led to
      a large push forward towards identifying common genetic variants that contribute
      to complex traits. However, despite many attempts, the search for common disease
      predisposing variants in childhood developmental disorders has largely failed.
      Recently, a role for rare causal variants and de novo mutations is emerging in
      the genetic architecture of some of these disorders, particularly those that
      incur a large degree of selection against the phenotype. In this paper, we
      examine these data and use classic genetic epidemiological approaches to gain
      insights into the genetic architecture of ASD. Future studies using next
      generation sequencing should elucidate the precise role de novo mutations play in
      disorders traditionally thought to have resulted from polygenic or common
      disease, common variants inheritance.

PMID- 21740539
TI  - Ten-year experiences with Tetanus at a Tertiary hospital in Northwestern
      Tanzania: A retrospective review of 102 cases.
AB  - BACKGROUND: Tetanus is still a major health problem in developing countries and
      it is associated with a high morbidity and mortality rate. There is paucity of
      published data regarding the management of tetanus in Tanzania, especially the
      study area. This study was conducted to describe our own experiences with tetanus
      outlining the clinical characteristics and treatment outcome of tetanus patients
      in our environment and to identify predictors of outcome of these patients.
      METHODS: This was a ten-year period retrospective study of patients who presented
      with a clinical diagnosis of tetanus at Bugando Medical Centre between January
      2001 and December 2010. Data was analyzed using SPSS computer software system.
      RESULTS: A total of 102 patients were studied. The male to female ratio was 11.8:
      1. The majority of patients (74.5%) were aged < 40 years and 51.0% of them were
      farmers. Only 23.5% of patients had prior tetanus immunization. 53.5% of patients
      had a reasonably identifiable acute injury prior to the onset of tetanus and
      commonly involved the lower limbs (53.8%). The majority of patients (97.1%) had
      generalized tetanus. The mean incubation period and period of onset were 8.62 +/-
      4.34 and 3.8 +/- 2.2 days respectively. Complication rate was 54.9%. The average
      overall duration of hospitalization was 34.12 +/- 38.44 days (1-120 days).
      Mortality rate was 43.1%. According to multivariate logistic regression analysis,
      the age >= 40 years (P = 0.002), incubation period < 7 days (P = 0.014),
      tracheostomy (P = 0.004), severity of tetanus (P = 0.001) and need for
      ventilatory support (P = 0.013) were found to be significantly associated with
      higher mortality. CONCLUSION: Tetanus remains a major public health problem in
      our centre and still carries unacceptably high morbidity and mortality despite
      the available advanced management facilities including ICU care. Young adult
      males are commonly affected. The incidence of tetanus can be reduced
      significantly by an effective immunization program and proper wound management of
      the patients. Early recognition, intense support and prompt treatment improves
      morbidity and mortality of patients diagnosed with tetanus.

PMID- 21740538
TI  - Use of vitamin supplements and risk of total cancer and cardiovascular disease
      among the Japanese general population: a population-based survey.
AB  - BACKGROUND: Despite the popular use of vitamin supplements and several
      prospective cohort studies investigating their effect on cancer incidence and
      cardiovascular disease (CVD), scientific data supporting their benefits remain
      controversial. Inconsistent results may be partly explained by the fact that use
      of supplements is an inconsistent behavior in individuals. We examined whether
      vitamin supplement use patterns affect cancer and CVD risk in a population-based
      cohort study in Japan. METHODS: A total of 28,903 men and 33,726 women in the
      Japan Public Health Center-based Prospective Study cohort, who answered questions
      about vitamin supplement use in the first survey from 1990-1994 and the second
      survey from 1995-1998, were categorized into four groups (never use, past use,
      recent use, and consistent use) and followed to the end of 2006 for cancer and
      2005 for CVD. Sex-specific hazard ratios (HRs) and 95% confidence intervals (95%
      CIs) were used to describe the relative risks of cancer and CVD associated with
      vitamin supplement use. RESULTS: During follow-up, 4501 cancer and 1858 CVD cases
      were identified. Multivariate adjusted analysis revealed no association of any
      pattern of vitamin supplement use with the risk of cancer and CVD in men. In
      women, consistent use was associated with lower risk of CVD (HR 0.60, 95% CI 0.41
      0.89), whereas past (HR 1.17, 95% CI 1.02-1.33) and recent use (HR 1.24, 95% CI
      1.01-1.52) were associated with higher risk of cancer. CONCLUSIONS: To our
      knowledge, this is the first prospective cohort study to examine simultaneously
      the associations between vitamin supplement use patterns and risk of cancer and
      CVD. This prospective cohort study demonstrated that vitamin supplement use has
      little effect on the risk of cancer or CVD in men. In women, however, consistent
      vitamin supplement use might reduce the risk of CVD. Elevated risk of cancer
      associated with past and recent use of vitamin supplements in women may be partly
      explained by preexisting diseases or unhealthy background, but we could not
      totally control for this in our study.

PMID- 21740540
TI  - The Maastricht Ultrasound Shoulder pain trial (MUST): ultrasound imaging as a
      diagnostic triage tool to improve management of patients with non-chronic
      shoulder pain in primary care.
AB  - BACKGROUND: Subacromial disorders are considered to be one of the most common
      pathologies affecting the shoulder. Optimal therapy for shoulder pain (SP) in
      primary care is yet unknown, since clinical history and physical examination do
      not provide decisive evidence as to the patho-anatomical origin of the symptoms.
      Optimal decision strategies can be furthered by applying ultrasound imaging (US),
      an accurate method in diagnosing SP, demonstrating a clear relationship between
      diagnosis and available therapies. Yet, the clinical cost-effectiveness of
      applying US in the management of SP in primary care has not been studied. The aim
      of this paper is to describe the design and methods of a trial assessing the cost
      effectiveness of ultrasound imaging as a diagnostic triage tool to improve
      management of primary care patients with non-chronic shoulder pain.
      METHODS/DESIGN: This randomised controlled trial (RCT) will involve 226 adult
      patients with suspected subacromial disorders recruited by general practitioners.
      During a Qualification period of two weeks, patients receive care as usual as
      advised by the Dutch College of General Practitioners, and patients are referred
      for US. Patients with insufficient improvement qualify for the RCT. These
      patients are then randomly assigned to the intervention or the control group. The
      therapies used in both groups are the same (corticosteroid injections, referral
      to a physiotherapist or orthopedic surgeon) except that therapies used in the
      intervention group will be tailored based on the US results. Ultrasound diagnosed
      disorders include tendinopathy, calcific tendinitis, partial and full thickness
      tears, and subacromial bursitis. The primary outcome is patient-perceived
      recovery at 52 weeks, using the Global Perceived Effect questionnaire. Secondary
      outcomes are disease specific and generic quality of life, cost-effectiveness,
      and the adherence to the initial applied treatment. Outcome measures will be
      assessed at baseline, 13, 26, 39 and 52 weeks after inclusion. An economic
      evaluation will be performed from both a health care and societal perspective
      with a time horizon of 52 weeks. DISCUSSION: The results of this trial will give
      unique evidence regarding the cost-effectiveness of US as a diagnostic triage
      tool in the management of SP in primary care.

PMID- 21740541
TI  - Transforming growth factor beta 869C/T and interleukin 6 -174G/C polymorphisms
      relate to the severity and progression of bone-erosive damage detected by
      ultrasound in rheumatoid arthritis.
AB  - INTRODUCTION: Single nucleotide polymorphisms (SNPs) of transforming growth
      factor beta (TGF-beta) and IL-6 genes (respectively, 869C/T and -174G/C) have
      been associated with radiographic severity of bone-erosive damage in patients
      with rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive
      than radiography in detecting bone erosion. We analyzed the association between
      TGF-beta 869C/T and IL-6 -174G/C SNPs and bone-erosive damage, evaluated by US,
      in a cohort of patients with severely active RA. METHODS: Seventy-seven patients
      were enrolled before beginning anti-TNF treatment. Disease activity was measured
      using the disease activity score in 28 joints, and the clinical response was
      evaluated according to the European League Against Rheumatism response criteria.
      Rheumatoid factor (RF) and anticitrullinated protein/peptide antibodies (ACPAs)
      were detected. The 869C/T TGF-beta and -174G/C IL-6 SNPs were analyzed by PCR
      amplification. US was performed to assess the bone surfaces of
      metacarpophalengeal (MCP), proximal interphalangeal (PIP) and metatarsophalangeal
      (MTP) joints by obtaining multiplanar scans. According to the number of erosions
      per joint, a semiquantitative score ranging from 0 to 3 was calculated in each
      anatomical site to obtain a MCP total erosion score (TES), a PIP TES and a MTP
      TES, all ranging from 0 to 30, and a global patient TES calculated as the sum of
      these scores (range, 0 to 90). RESULTS: Patients carrying the TGF-beta 869TT
      genotype showed a statistically significant lower MTP TES than those with the CC
      or CT genotype (mean MTP TES +/- standard deviation for 869TT 6.3 +/- 5.7 vs.
      869CC/CT 11.7 +/- 7.8; P = 0.011). Interestingly, patients with the TT genotype
      showed dichotomous behavior that was dependent on autoantibody status. In the
      presence of ACPAs and/or RF, the TT genotype was associated with lower erosion
      scores at all anatomical sites compared with the CC and CT genotypes. Conversely,
      the same 869TT patients showed higher erosion scores in the absence of ACPAs or
      RF. CONCLUSIONS: In RA patients, TGF-beta 869C/T SNPs could influence the bone
      erosive damage as evaluated by US. The serological autoantibody status (ACPAs and
      RF) can modulate this interaction.

PMID- 21740542
TI  - Prevalence of accessory deep peroneal nerve in referred patients to an
      electrodiagnostic medicine clinic.
AB  - BACKGROUND: Accessory Deep Peroneal Nerve (ADPN) is an anatomic variation that
      can potentially cause disturbance in electrodiagnostic studies. This anomaly
      could be detected by nerve conduction studies. There are no recent updates about
      prevalence of this anatomic variation. Electrodiagnostic medicine clinic is the
      best environment for detecting presence and prevalence of this nerve, so present
      study enrolled. MATERIALS & METHODS: In this cross sectional descriptive study
      that take place from March 2009 to July 2010, 230 cases comprising 460 legs
      referred for electrodiagnostic studies of upper limbs problems participated in
      the study. Compound muscle action potential (CMAP) and Nerve conduction Velocity
      (NCV) of Deep Peroneal Nerve (DPN) were measured by using EMG machine by
      stimulating DPN at knee, ankle and lateral malleolous areas accordingly, with
      recording from extensor digitorum brevis muscle. Results were analyzed and
      conclusion made. RESULTS: The study population included 120 females (52%) and 110
      (47%) males with mean age of 42.1 +/- 13.5 years. ADPN was detected in 28
      patients (12%). Among them,10(17.9%) had bilateral ADPN and in remained 18 cases
      (82.1%) APN was unilateral. In 8 patients there was no recorded CMAP from EDB by
      proximal and distal stimulation implying EDB agenesis. Gender distribution was
      similar which means half of the cases (14 patients) belonged to each gender.
      CONCLUSION: The prevalence of ADPN in this study was 12.2%, (17.9% bilateral and
      82.1% unilateral).

PMID- 21740543
TI  - 1alpha,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-beta
      peptide(1-40) from mouse brain across the blood-brain barrier.
AB  - BACKGROUND: Cerebrovascular dysfunction has been considered to cause impairment
      of cerebral amyloid-beta peptide (Abeta) clearance across the blood-brain barrier
      (BBB). Further, low levels of vitamin D are associated with increased risk of
      Alzheimer's disease, as well as vascular dysfunction. The purpose of the present
      study was to investigate the effect of 1alpha,25-dihydroxyvitamin D3
      (1,25(OH)2D3), an active form of vitamin D, on cerebral Abeta clearance from
      mouse brain. METHODS: The elimination of [125I]hAbeta(1-40) from mouse brain was
      examined by using the Brain Efflux Index method to determine the remaining amount
      of [125I]hAbeta(1-40) radioactivity after injection into the cerebral cortex.
      [125I]hAbeta(1-40) internalization was analyzed using conditionally immortalized
      mouse brain capillary endothelial cells (TM-BBB4). RESULTS: Twenty-four hours
      after intraperitoneal injection of 1,25(OH)2D3 (1 MUg/mouse), [125I]hAbeta(1-40)
      elimination from mouse brain was increased 1.3-fold, and the level of endogenous
      Abeta(1-40) in mouse brain was reduced. These effects were observed at 24 h after
      i.p. injection of 1,25(OH)2D3, while no significant effect was observed at 48 or
      72 h. Vitamin D receptor (VDR) mRNA was detected in mouse brain capillaries,
      suggesting that 1,25(OH)2D3 has a VDR-mediated genomic action. Furthermore,
      forskolin, which activates mitogen-activated protein kinase kinase (MEK),
      enhanced [125I]hAbeta(1-40) elimination from mouse brain. Forskolin also enhanced
      [125I]hAbeta(1-40) internalization in TM-BBB4 cells, and this enhancement was
      inhibited by a MEK inhibitor, suggesting involvement of non-genomic action.
      CONCLUSIONS: The active form of vitamin D, 1,25(OH)2D3, appears to enhance brain
      to-blood Abeta(1-40) efflux transport at the BBB through both genomic and non
      genomic actions. Compounds activating these pathways may be candidate agents for
      modulating Abeta(1-40) elimination at the BBB.

PMID- 21740544
TI  - Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent.
AB  - BACKGROUND: Age is the major risk factor for many neurodegenerative diseases,
      including Alzheimer's disease (AD). There is an accumulation of amyloid-beta
      peptides (Abeta) in both the AD brain and the normal aging brain. Clearance of
      Abeta from the brain occurs via active transport at the blood-brain barrier (BBB)
      and blood-cerebrospinal fluid barrier (BCSFB). With increasing age, the
      expression of the Abeta efflux transporters is decreased and the Abeta influx
      transporter expression is increased at the BBB, adding to the amyloid burden in
      the brain. Expression of the Abeta transporters at the choroid plexus (CP)
      epithelium as a function of aging was the subject of this study. METHODS: This
      project investigated the changes in expression of the Abeta transporters, the low
      density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (P-gp),
      LRP-2 (megalin) and the receptor for advanced glycation end-products (RAGE) at
      the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months,
      using real time RT-PCR to measure transporter mRNA expression, and
      immunohistochemistry (IHC) to measure transporter protein in isolated rat CP.
      RESULTS: There was an increase in the transcription of the Abeta efflux
      transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP
      2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased
      Abeta42 concentration in the CP, as measured by quantitative IHC, was associated
      with these Abeta transporter alterations. CONCLUSIONS: Age-dependent alterations
      in the CP Abeta transporters are associated with a decrease in Abeta42
      accumulation in the CP, and are reciprocal to the changes seen in these
      transporters at the BBB, suggesting a possible compensatory role for the BCSFB in
      Abeta clearance in aging.

PMID- 21740545
TI  - Comparative review of three cost-effectiveness models for rotavirus vaccines in
      national immunization programs; a generic approach applied to various regions in
      the world.
AB  - BACKGROUND: This study aims to critically review available cost-effectiveness
      models for rotavirus vaccination, compare their designs using a standardized
      approach and compare similarities and differences in cost-effectiveness outcomes
      using a uniform set of input parameters. METHODS: We identified various models
      used to estimate the cost-effectiveness of rotavirus vaccination. From these,
      results using a standardized dataset for four regions in the world could be
      obtained for three specific applications. RESULTS: Despite differences in the
      approaches and individual constituting elements including costs, QALYs Quality
      Adjusted Life Years and deaths, cost-effectiveness results of the models were
      quite similar. Differences between the models on the individual components of
      cost-effectiveness could be related to some specific features of the respective
      models. Sensitivity analysis revealed that cost-effectiveness of rotavirus
      vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality
      and discount rates, in particular that for QALYs. CONCLUSIONS: The comparative
      approach followed here is helpful in understanding the various models selected
      and will thus benefit (low-income) countries in designing their own cost
      effectiveness analyses using new or adapted existing models. Potential users of
      the models in low and middle income countries need to consider results from
      existing studies and reviews. There will be a need for contextualization
      including the use of country specific data inputs. However, given that the
      underlying biological and epidemiological mechanisms do not change between
      countries, users are likely to be able to adapt existing model designs rather
      than developing completely new approaches. Also, the communication established
      between the individual researchers involved in the three models is helpful in the
      further development of these individual models. Therefore, we recommend that this
      kind of comparative study be extended to other areas of vaccination and even
      other infectious disease interventions.

PMID- 21740546
TI  - Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration
      in Parkinson's disease and stroke model rats.
AB  - BACKGROUND: Parkinson's disease (PD) and cerebral ischemia are chronic and acute
      neurodegenerative diseases, respectively, and onsets of these diseases are
      thought to be induced at least by oxidative stress. PD is caused by decreased
      dopamine levels in the substantia nigra and striatum, and cerebral ischemia
      occurs as a result of local reduction or arrest of blood supply. Although a
      precursor of dopamine and inhibitors of dopamine degradation have been used for
      PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell
      death progresses during treatment. Reagents that prevent oxidative stress-induced
      cell death are therefore necessary for fundamental therapies for PD and cerebral
      ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays
      roles in transcriptional regulation and anti-oxidative stress, and loss of its
      function is thought to result in the onset of PD. Superfluous oxidation of
      cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such
      oxidized DJ-1 has been observed in patients with the sporadic form of PD.
      RESULTS: In this study, a compound, comp-23, that binds to DJ-1 was isolated by
      virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y
      cells and primary neuronal cells of the ventral mesencephalon but not that of DJ
      1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific
      to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS)
      induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore,
      comp-23 prevented dopaminergic cell death in the substantia nigra and restored
      movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model
      rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats
      that had been induced by middle cerebral artery occlusion. Protective activity of
      comp-23 seemed to be stronger than that of previously identified compound B.
      CONCLUSIONS: The results indicate that comp-23 exerts a neuroprotective effect by
      reducing ROS-mediated neuronal injury, suggesting that comp-23 becomes a lead
      compound for PD and ischemic neurodegeneration therapies.

PMID- 21740548
TI  - SAMHD1: a new insight into HIV-1 restriction in myeloid cells.
AB  - Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins
      from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1
      infection through proteasomal degradation of a putative restriction factor. Two
      recent studies discovered the cellular protein SAMHD1 to be this restriction
      factor, demonstrating that Vpx induces proteasomal degradation of SAMHD1 and
      enhances HIV-1 infection in myeloid-lineage cells. SAMHD1 functions as a myeloid
      cell-specific HIV-1 restriction factor by inhibiting viral DNA synthesis. Here we
      discuss the implications of these findings in delineating the mechanisms of HIV-1
      restriction in myeloid-lineage cells and the potential role of Vpx in lentiviral
      pathogenesis.

PMID- 21740549
TI  - An RNA interference screen for identifying downstream effectors of the p53 and
      pRB tumour suppressor pathways involved in senescence.
AB  - BACKGROUND: Cellular senescence is an irreversible cell cycle arrest that normal
      cells undergo in response to progressive shortening of telomeres, changes in
      telomeric structure, oncogene activation or oxidative stress and acts as an
      important tumour suppressor mechanism. RESULTS: To identify the downstream
      effectors of the p53-p21 and p16-pRB tumour suppressor pathways crucial for
      mediating entry into senescence, we have carried out a loss-of-function RNA
      interference screen in conditionally immortalised human fibroblasts that can be
      induced to rapidly undergo senescence, whereas in primary cultures senescence is
      stochastic and occurs asynchronously. These cells are immortal but undergo a
      rapid irreversible arrest upon activation of the p53-p21 and p16-pRB pathways
      that can be readily bypassed upon their inactivation. The primary screen
      identified 112 known genes including p53 and another 29 shRNAmirs targetting as
      yet unidentified loci. Comparison of these known targets with genes known to be
      up-regulated upon senescence in these cells, by micro-array expression profiling,
      identified 4 common genes TMEM9B, ATXN10, LAYN and LTBP2/3. Direct silencing of
      these common genes, using lentiviral shRNAmirs, bypassed senescence in the
      conditionally immortalised cells. CONCLUSION: The senescence bypass screen
      identified TMEM9B, ATXN10, LAYN and LTBP2/3 as novel downstream effectors of the
      p53-p21 and p16-pRB tumour suppressor pathways. Although none of them has
      previously been linked to cellular senescence, TMEM9B has been suggested to be an
      upstream activator of NF-kappaB signalling which has been found to have a causal
      role in promoting senescence. Future studies will focus on determining on how
      many of the other primary hits also have a casual role in senescence and what is
      the mechanism of action.

PMID- 21740547
TI  - Construction of an American mink bacterial artificial chromosome (BAC) library
      and sequencing candidate genes important for the fur industry.
AB  - BACKGROUND: Bacterial artificial chromosome (BAC) libraries continue to be
      invaluable tools for the genomic analysis of complex organisms. Complemented by
      the newly and fast growing deep sequencing technologies, they provide an
      excellent source of information in genomics projects. RESULTS: Here, we report
      the construction and characterization of the CHORI-231 BAC library constructed
      from a Danish-farmed, male American mink (Neovison vison). The library contains
      approximately 165,888 clones with an average insert size of 170 kb, representing
      approximately 10-fold coverage. High-density filters, each consisting of 18,432
      clones spotted in duplicate, have been produced for hybridization screening and
      are publicly available. Overgo probes derived from expressed sequence tags
      (ESTs), representing 21 candidate genes for traits important for the mink
      industry, were used to screen the BAC library. These included candidate genes for
      coat coloring, hair growth and length, coarseness, and some receptors potentially
      involved in viral diseases in mink. The extensive screening yielded positive
      results for 19 of these genes. Thirty-five clones corresponding to 19 genes were
      sequenced using 454 Roche, and large contigs (184 kb in average) were assembled.
      Knowing the complete sequences of these candidate genes will enable confirmation
      of the association with a phenotype and the finding of causative mutations for
      the targeted phenotypes.Additionally, 1577 BAC clones were end sequenced; 2505
      BAC end sequences (80% of BACs) were obtained. An excess of 2 Mb has been
      analyzed, thus giving a snapshot of the mink genome. CONCLUSIONS: The
      availability of the CHORI-321 American mink BAC library will aid in
      identification of genes and genomic regions of interest. We have demonstrated how
      the library can be used to identify specific genes of interest, develop genetic
      markers, and for BAC end sequencing and deep sequencing of selected clones. To
      our knowledge, this is the first report of 454 sequencing of selected BAC clones
      in mammals and re-assures the suitability of this technique for obtaining the
      sequence information of genes of interest in small genomics projects. The BAC end
      sequences described in this paper have been deposited in the GenBank data library
      [HN339419-HN341884, HN604664-HN604702]. The 454 produced contigs derived from
      selected clones are deposited with reference numbers [GenBank: JF288166-JF288183
      &JF310744].

PMID- 21740550
TI  - Treatments for reversing warfarin anticoagulation in patients with acute
      intracranial hemorrhage: a structured literature review.
AB  - STUDY OBJECTIVE: The acute management of patients on warfarin with spontaneous or
      traumatic intracranial hemorrhage continues to be debated in the medical
      literature. The objective of this paper was to conduct a structured review of the
      medical literature and summarize the advantages and risks of the available
      treatment options for reversing warfarin anticoagulation in patients who present
      to the emergency department with acute intracranial hemorrhage. METHODS: A
      structured literature search and review of articles relevant to intracranial
      hemorrhage and warfarin and treatment in the emergency department was performed.
      Databases for PubMed, CINAHL, and Cochrane EBM Reviews were electronically
      searched using keywords covering the concepts of anticoagulation drugs,
      intracranial hemorrhage (ICH), and treatment. The results generated by the search
      were limited to English- language articles and reviewed for relevance to our
      topic. The multiple database searches revealed 586 papers for review for possible
      inclusion. The final consensus of our comprehensive search strategy was a total
      of 23 original studies for inclusion in our review. RESULTS: Warfarin not only
      increases the risk of but also the severity of ICH by causing hematoma expansion.
      Prothrombin complex concentrate is statistically significantly faster at
      correcting the INR compared to fresh frozen plasma transfusions. Recombinant
      factor VIIa appears to rapidly reverse warfarin's effect on INR; however, this
      treatment is not FDA-approved and is associated with a 5% thromboembolic event
      rate. Slow intravenous dosing of vitamin K is recommended in patients with ICH.
      The 30-day risk for ischemic stroke after discontinuation of warfarin therapy was
      3-5%. The risks of not reversing the anticoagulation in ICH generally outweigh
      the risk of thrombosis in the acute setting. CONCLUSIONS: Increasing numbers of
      patients are on anticoagulation including warfarin. There is no uniform standard
      for reversing warfarin in intracranial hemorrhage. Intravenous vitamin K in
      addition to fresh frozen plasma or prothrombin complex concentrate is recommended
      be used to reverse warfarin-associated intracranial hemorrhage. No mortality
      benefit for one treatment regimen over another has been shown. Emergency
      physicians should know their hospital's available warfarin reversal options and
      be comfortable administering these treatments to critically ill patients.

PMID- 21740551
TI  - Statin pre-treatment is associated with lower platelet activity and favorable
      outcome in patients with acute non-cardio-embolic ischemic stroke.
AB  - INTRODUCTION: Statins reportedly have anti-inflammatory and anti-thrombotic
      effects aside from cholesterol-lowering. This study aimed to evaluate the effect
      of pre-existing statin use on platelet activation markers and clinical outcome in
      acute ischemic stroke patients. METHODS: This prospective study evaluated 172
      patients with acute ischemic stroke divided in two groups: patients with pre
      existing statin (n = 43) and without pre-existing statin (66 cases with statins
      initiated post-stroke and 63 without statin treatment). Platelet activation
      markers (CD62P and CD63) were measured by flow cytometry at different time points
      after stroke and analyzed with clinical outcome. RESULTS: The CD62P and CD63
      expressions on platelets were significantly lower in the patients with pre
      existing statin use compared to the patients without pre-existing statin use on
      Day 1 post-stroke (p < 0.05). The CD62P expression was significantly lower in the
      patients with pre-existing statin use on 90 days after the acute stroke (p <
      0.05). Patients with pre-existing statin use had lower incidences of early
      neurologic deterioration (END) than those without treatment (p < 0.05). Among
      several baseline clinical variables, admission NIHSS score, history of coronary
      artery disease, and pre-existing statin use were independent predictions of good
      clinical outcome at three months. CONCLUSIONS: Pre-existing statin use is
      associated with decreased platelet activity as well as improved clinical outcome
      and reduced END in patients with acute ischemic stroke.

PMID- 21740552
TI  - Preventing the next 'SARS' - European healthcare workers' attitudes towards
      monitoring their health for the surveillance of newly emerging infections:
      qualitative study.
AB  - BACKGROUND: Hospitals are often the epicentres of newly circulating infections.
      Healthcare workers (HCWs) are at high risk of acquiring infectious diseases and
      may be among the first to contract emerging infections. This study aims to
      explore European HCWs' perceptions and attitudes towards monitoring their absence
      and symptom reports for surveillance of newly circulating infections. METHODS: A
      qualitative study with thematic analysis was conducted using focus group
      methodology. Forty-nine hospital-based HCWs from 12 hospitals were recruited to
      six focus groups; two each in England and Hungary and one each in Germany and
      Greece. RESULTS: HCWs perceived risk factors for occupationally acquired
      infectious diseases to be 1.) exposure to patients with undiagnosed infections
      2.) break-down in infection control procedures 3.) immuno-naivety and 4.)
      symptomatic colleagues. They were concerned that a lack of monitoring and
      guidelines for infectious HCWs posed a risk to staff and patients and felt
      employers failed to take a positive interest in their health. Staffing demands
      and loss of income were noted as pressures to attend work when unwell. In the UK,
      Hungary and Greece participants felt monitoring staff absence and the routine
      disclosure of symptoms could be appropriate provided the effectiveness and
      efficiency of such a system were demonstrable. In Germany, legislation, privacy
      and confidentiality were identified as barriers. All HCWs highlighted the need
      for knowledge and structural improvements for timelier recognition of emerging
      infections. These included increased suspicion and awareness among staff and
      standardised, homogenous absence reporting systems. CONCLUSIONS: Monitoring
      absence and infectious disease symptom reports among HCWs may be a feasible means
      of surveillance for emerging infections in some settings. A pre-requisite will be
      tackling the drivers for symptomatic HCWs to attend work.

PMID- 21740553
TI  - Highly pathogenic avian influenza H5N1 virus could partly be evacuated by
      pregnant BALB/c mouse during abortion or preterm delivery.
AB  - The highly pathogenic avian influenza H5N1 virus is one of candidates for future
      pandemic. Since H5N1 viruses had previously been isolated only from avian
      species, the outbreak raised questions about the ability of these viruses to
      cause severe disease and death in humans. Pregnant women are at increased risk
      for influenza-associated illness and death. However, little is known about
      whether influenza viruses could transmit to the fetus through the placenta, and
      the effects of abortion and preterm delivery to maternal influenza infection are
      not well understood. We found that the H5N1 viruses could vertical transmit to
      the fetus through the placenta in the BALB/c mouse model, and the viruses could
      partly be evacuated by the pregnant mice during abortion or preterm delivery.
      This study may further our understanding about the transmission of this highly
      pathogenic avian influenza viruses, supply optimized clinical treatment method
      for pregnant women, and shed some light on better preventing and controlling for
      future potential outbreak of H5N1 influenza pandemic.

PMID- 21740554
TI  - Mycoplasma gallisepticum infection in the grey partridge Perdix perdix: outbreak
      description, histopathology, biochemistry and antioxidant parameters.
AB  - BACKGROUND: The grey partridge is an important game bird in Europe that has
      declined considerably over the last decades. The production and release of farm
      bred birds can be threatened by infectious agents. The objective of this study
      was to describe the outbreak, pathology, and blood and tissue biochemical
      responses in a flock of grey partridges naturally infected with Mycoplasma
      gallisepticum. RESULTS: Morbidity and mortality rates were 100% and 60%,
      respectively. Necropsy revealed an accumulation of caseous exudate within the
      infraorbital sinuses, tracheitis, pneumonia and airsacculitis. There were
      significant increases in activities of lactate dehydrogenase, creatine kinase and
      amylase, and levels of total protein and glucose in Mycoplasma-infected birds
      when compared to control. Catalase showed significantly lower activity in the
      heart, lungs, liver and gonads of Mycoplasma-infected birds. Glutathione-S
      transferase activity was elevated in the eye and the associated infraorbital
      sinus and kidneys, and decreased in the liver. Decreased levels of reduced
      glutathione were found in the heart, kidneys, liver and gonads. The activity of
      glutathione reductase was lower only in the lungs. Compared to healthy birds,
      mycoplasmosis in the grey partridge caused significant differences in the level
      of lipid peroxidation in lungs and plasma (p < 0.05), while the ferric reducing
      antioxidant power was lower in the heart and kidneys (p < 0.01). Significant
      correlations among responses of the antioxidant parameters were found namely in
      the heart, lungs, spleen, liver and plasma. There were also numerous significant
      inter-tissue correlations of all the studied antioxidant parameters. CONCLUSIONS:
      The present study demonstrates the high susceptibility of grey partridges to
      natural infection by M. gallisepticum, the severity of the disease based on
      histopathology, and the modulation of blood chemical profiles and oxidative
      stress-associated parameters in the avian hosts, thus enhancing the understanding
      of the pathogenesis of mycoplasmosis in birds. Moreover, the reported reference
      values can be useful for the evaluation of the state of health in grey
      partridges.

PMID- 21740555
TI  - Dose-response relationship between arsenic exposure and the serum enzymes for
      liver function tests in the individuals exposed to arsenic: a cross sectional
      study in Bangladesh.
AB  - BACKGROUND: Chronic arsenic exposure has been shown to cause liver damage.
      However, serum hepatic enzyme activity as recognized on liver function tests
      (LFTs) showing a dose-response relationship with arsenic exposure has not yet
      been clearly documented. The aim of our study was to investigate the dose
      response relationship between arsenic exposure and major serum enzyme marker
      activity associated with LFTs in the population living in arsenic-endemic areas
      in Bangladesh. METHODS: A total of 200 residents living in arsenic-endemic areas
      in Bangladesh were selected as study subjects. Arsenic concentrations in the
      drinking water, hair and nails were measured by Inductively Coupled Plasma Mass
      Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as
      follows, based on concentrations of arsenic in the drinking water, as well as in
      subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme
      activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and
      alanine transaminase (ALT) were then assayed. RESULTS: Arsenic concentrations in
      the subjects' hair and nails were positively correlated with arsenic levels in
      the drinking water. As regards the exposure-response relationship with arsenic in
      the drinking water, the respective activities of ALP, AST and ALT were found to
      be significantly increased in the high-exposure groups compared to the lowest
      exposure groups before and after adjustments were made for different covariates.
      With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT
      activity profiles assumed a similar shape of dose-response relationship, with
      very few differences seen in the higher groups compared to the lowest group, most
      likely due to the temporalities of exposure metrics. CONCLUSIONS: The present
      study demonstrated that arsenic concentrations in the drinking water were
      strongly correlated with arsenic concentrations in the subjects' hair and nails.
      Further, this study revealed a novel exposure- and dose- response relationship
      between arsenic exposure metrics and serum hepatic enzyme activity. Elevated
      serum hepatic enzyme activities in the higher exposure gradients provided new
      insights into arsenic-induced liver toxicity that might be helpful for the early
      prognosis of arsenic-induced liver diseases.

PMID- 21740556
TI  - A new resorbable device for ligation of blood vessels - A pilot study.
AB  - BACKGROUND: During surgery, controlled haemostasis to prevent blood loss is vital
      for a successful outcome. It can be difficult to ligate vessels located deep in
      the abdomen. A device that is easy to use and enables secure ligatures could be
      beneficial. Cable ties made of nylon have been used for ligation but the non
      resorbable material caused tissue reactions. The objective of this study was to
      use a resorbable material to construct a device with a self-locking mechanism and
      to test its mechanical strength and ligation efficiency. METHODS: The device was
      manufactured by injection moulding of polydioxanone, a resorbable polymer used
      for suture materials. Polydioxanone with inherent viscosities of 1.9 dL/g and 1.3
      dL/g were tested. The device consisted of a perforated flexible band which could
      be pulled through a case with a locking mechanism. After a first version of the
      device had been tested, some improvements were made. The locking case was
      downsized, corners were rounded off, the band was made thicker and the mould was
      redesigned to produce longer devices. Tensile tests were performed with the
      second version.The first version of the device was used to ligate the ovarian
      pedicle in a euthanized dog and to test echogenicity of the device with
      ultrasound. Compression of vessels of the ovarian pedicle was examined by
      histology. Both versions of the device were tested for haemostasis of and tissue
      grip on renal arteries in six anaesthetised pigs. RESULTS: The tensile strength
      of the flexible band of the devices with inherent viscosity of 1.9 dL/g was 50.1
      +/- 5.5 N (range 35.2-62.9 N, n = 11) and the devices with inherent viscosity of
      1.3 dL/g had a tensile strength of 39.8 +/- 8.1 N (range 18.6-54.2 N, n = 11).
      Injection moulding of the polymer with lower inherent viscosity resulted in a
      longer flow distance.Both versions of the device had an effective tissue grip and
      complete haemostasis of renal arteries was verified. The device attached to the
      ovarian pedicle could be seen with ultrasound, and vessel compression and
      occlusion were verified by histology. CONCLUSIONS: Tests of functionality of the
      device showed complete haemostasis and good tissue grip. Devices with a band of
      sufficient length were easily applied and tightened in tissue.

PMID- 21740557
TI  - Evidence for acquisition of virulence effectors in pathogenic chytrids.
AB  - BACKGROUND: The decline in amphibian populations across the world is frequently
      linked to the infection of the chytrid fungus Batrachochytrium dendrobatidis
      (Bd). This is particularly perplexing because Bd was only recently discovered in
      1999 and no chytrid fungus had previously been identified as a vertebrate
      pathogen. RESULTS: In this study, we show that two large families of known
      virulence effector genes, crinkler (CRN) proteins and serine peptidases, were
      acquired by Bd from oomycete pathogens and bacteria, respectively. These two
      families have been duplicated after their acquisition by Bd. Additional selection
      analyses indicate that both families evolved under strong positive selection,
      suggesting that they are involved in the adaptation of Bd to its hosts.
      CONCLUSIONS: We propose that the acquisition of virulence effectors, in
      combination with habitat disruption and climate change, may have driven the Bd
      epidemics and the decline in amphibian populations. This finding provides a
      starting point for biochemical investigations of chytridiomycosis.

PMID- 21740558
TI  - Higher body mass index may induce asthma among adolescents with pre-asthmatic
      symptoms: a prospective cohort study.
AB  - BACKGROUND: Limited studies have prospectively examined the role of body mass
      index (BMI) as a major risk factor for asthma during adolescence. This study
      investigates whether BMI is associated with increased risk of developing
      physician-diagnosed asthma during 12-month follow-up among adolescents with
      undiagnosed asthma-like symptoms at baseline. METHODS: A total of 4,052
      adolescents with undiagnosed asthma-like symptoms at baseline were re-examined
      after a 12-month follow-up. Asthma cases were considered confirmed only after
      diagnosis by a physician based on the New England core and International Study of
      Asthma and Allergies in Childhood (ISAAC) criteria video questionnaires, and
      accompanying pulmonary function tests. Logistic regression analyses were used to
      evaluate the relationship of BMI and the risk of acquiring asthma. RESULTS: The
      results indicated that girls with higher BMI were at an increased risk of
      developing asthma during the 12-month follow-up. The odds ratios for girls
      developing physician-diagnosed asthma were 1.75 (95% CI = 1.18-2.61) and 1.12
      (95% CI = 0.76-1.67), respectively, for overweight and obesity as compared to the
      normal weight reference group after adjustment for other covariates. A similar
      relationship was not observed for overweight and obese boys who were also
      significantly more active than their female counterparts. CONCLUSIONS: Increased
      BMI exaggerates the risk of acquiring asthma in symptomatic adolescent females
      but not in adolescent males. Thus, gender is an important modifier of BMI-related
      asthma risk. Additional research will be required to determine whether the
      increased asthma risk results from genetic, physiological or behavioural
      differences.

PMID- 21740559
TI  - Reconstructing genetic mating systems in the absence of parental information in
      colonially breeding waterbirds.
AB  - BACKGROUND: DNA-based studies have demonstrated that avian genetic mating systems
      vary widely, with many species deviating from long-assumed monogamy by practicing
      extra-pair paternity and conspecific brood parasitism. Colonially breeding
      waterbirds provide interesting models in which to investigate this question
      because they show nesting habits proposed to promote alternative reproductive
      strategies. However, little is known about the genetic mating systems of this
      group of birds, mainly due to difficulties in obtaining genetic data from
      incubating adults at nests that are necessary for conducting conventional
      parentage studies. Here, we inferred kinship patterns among offspring in broods
      of three co-distributed waterbird species, Wood Stork (Mycteria americana),
      Roseate Spoonbill (Platalea ajaja) and Great Egret (Ardea alba egretta), to
      investigate genetic mating system in the absence of parental data. RESULTS: Multi
      step analyses combining estimates of relatedness coefficients, formulation of
      relationship-hypotheses, significance testing of alternative hypotheses, and
      maximum-likelihood sibship reconstruction techniques revealed evidence that
      alternative reproductive strategies may be present in natural populations of Wood
      Storks and Roseate Spoonbills, whereas relatedness of co-nestlings diagnosed in
      the Great Egrets did not deviate from a hypothesis of genetic monogamy.
      Specifically, under this analytical framework, inferred kinship relationships
      revealed that Great Egret nests contained full-sibling nestlings (100%), with the
      Roseate Spoonbill (RS) and Wood Stork (WS) exhibiting proportions of half
      siblings (RS: 5%) and/or unrelated nestlings (RS: 24%; WS: 70%), patterns
      consistent with extra-pair paternity and conspecific brood parasitism,
      respectively. CONCLUSIONS: We provide evidence that genetic monogamy occurs in
      Brazilian natural breeding colonies of the Great Egret, but is not the sole
      reproductive strategy employed by the Wood Stork and the Roseate Spoonbill. In
      fact, extra-pair paternity and conspecific brood parasitism were common in the
      latter two species, with a combined frequency of 7.5% and 11.3% in Roseate
      Spoonbill and Wood Stork, respectively. Although geographically co-distributed,
      differences among these species may be due to variation in their life histories.
      From a methodological standpoint, the approach implemented here, although not
      free from limitations, can have broad application for analyzing systems with
      limited genealogical information and/or in studying similarly challenging
      organisms in which obtaining genetic data on complete families is problematic.

PMID- 21740560
TI  - Characterization of the small RNA component of the transcriptome from grain and
      sweet sorghum stems.
AB  - BACKGROUND: Sorghum belongs to the tribe of the Andropogoneae that includes
      potential biofuel crops like switchgrass, Miscanthus and successful biofuel crops
      like corn and sugarcane. However, from a genomics point of view sorghum has
      compared to these other species a simpler genome because it lacks the additional
      rounds of whole genome duplication events. Therefore, it has become possible to
      generate a high-quality genome sequence. Furthermore, cultivars exists that rival
      sugarcane in levels of stem sugar so that a genetic approach can be used to
      investigate which genes are differentially expressed to achieve high levels of
      stem sugar. RESULTS: Here, we characterized the small RNA component of the
      transcriptome from grain and sweet sorghum stems, and from F2 plants derived from
      their cross that segregated for sugar content and flowering time. We found that
      variation in miR172 and miR395 expression correlated with flowering time whereas
      variation in miR169 expression correlated with sugar content in stems.
      Interestingly, genotypic differences in the ratio of miR395 to miR395* were
      identified, with miR395* species expressed as abundantly as miR395 in sweet
      sorghum but not in grain sorghum. Finally, we provided experimental evidence for
      previously annotated miRNAs detecting the expression of 25 miRNA families from
      the 27 known and discovered 9 new miRNAs candidates in the sorghum genome.
      CONCLUSIONS: Sequencing the small RNA component of sorghum stem tissue provides
      us with experimental evidence for previously predicted microRNAs in the sorghum
      genome and microRNAs with a potential role in stem sugar accumulation and
      flowering time.

PMID- 21740561
TI  - One-shot genitalia are not an evolutionary dead end - regained male polygamy in a
      sperm limited spider species.
AB  - BACKGROUND: Monogynous mating systems with extremely low male mating rates have
      several independent evolutionary origins and are associated with drastic
      adaptations involving self-sacrifice, one-shot genitalia, genital damage, and
      termination of spermatogenesis immediately after maturation. The combination of
      such extreme traits likely restricts evolutionary potential perhaps up to the
      point of making low male mating rates irreversible and hence may constitute an
      evolutionary dead end. Here, we explore the case of a reversion to multiple
      mating from monogynous ancestry in golden orb-web spiders, Nephila senegalensis.
      RESULTS: Male multiple mating is regained by the loss of genital damage and
      sexual cannibalism but spermatogenesis is terminated with maturation, restricting
      males to a single loading of their secondary mating organs and a fixed supply of
      sperm. However, males re-use their mating organs and by experimentally mating
      males to many females, we show that the sperm supply is divided between
      copulations without reloading the pedipalps. CONCLUSION: By portioning their
      precious sperm supply, males achieve an average mating rate of four females which
      effectively doubles the maximal mating rate of their ancestors. A heritage of one
      shot genitalia does not completely restrict the potential to increase mating
      rates in Nephila although an upper limit is defined by the available sperm load.
      Future studies should now investigate how males use this potential in the field
      and identify selection pressures responsible for a reversal from monogynous to
      polygynous mating strategies.

PMID- 21740562
TI  - Dynamical basis for drug resistance of HIV-1 protease.
AB  - BACKGROUND: Protease inhibitors designed to bind to protease have become major
      anti-AIDS drugs. Unfortunately, the emergence of viral mutations severely limits
      the long-term efficiency of the inhibitors. The resistance mechanism of these
      diversely located mutations remains unclear. RESULTS: Here I use an elastic
      network model to probe the connection between the global dynamics of HIV-1
      protease and the structural distribution of drug-resistance mutations. The models
      for study are the crystal structures of unbounded and bound (with the substrate
      and nine FDA approved inhibitors) forms of HIV-1 protease. Coarse-grained
      modeling uncovers two groups that couple either with the active site or the flap.
      These two groups constitute a majority of the drug-resistance residues. In
      addition, the significance of residues is found to be correlated with their
      dynamical changes in binding and the results agree well with the complete
      mutagenesis experiment of HIV-1 protease. CONCLUSIONS: The dynamic study of HIV-1
      protease elucidates the functional importance of common drug-resistance mutations
      and suggests a unifying mechanism for drug-resistance residues based on their
      dynamical properties. The results support the robustness of the elastic network
      model as a potential predictive tool for drug resistance.

PMID- 21740563
TI  - A novel point mutation within the EDA gene causes an exon dropping in mature RNA
      in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal
      dysplasia.
AB  - BACKGROUND: X-linked anhidrotic ectodermal dysplasia is a disorder characterized
      by abnormal development of tissues and organs of ectodermal origin caused by
      mutations in the EDA gene. The bovine EDA gene encodes the ectodysplasin A, a
      membrane protein expressed in keratinocytes, hair follicles and sweat glands,
      which is involved in the interactions between cell and cell and/or cell and
      matrix. Four mutations causing ectodermal dysplasia in cattle have been described
      so far. RESULTS: We identified a new single nucleotide polymorphism (SNP) at the
      9th base of exon 8 in the EDA gene in two calves of Holstein Friesian cattle
      breed affected by ectodermal dysplasia. This SNP is located in the exonic
      splicing enhancer (ESEs) recognized by SRp40 protein. As a consequence, the
      spliceosome machinery is no longer able to recognize the sequence as exonic and
      causes exon skipping. The mutation determines the deletion of the entire exon
      (131 bp) in the RNA processing, causing a severe alteration of the protein
      structure and thus the disease. CONCLUSION: We identified a mutation, never
      described before, that changes the regulation of alternative splicing in the EDA
      gene and causes ectodermal dysplasia in cattle. The analysis of the SNP allows
      the identification of carriers that can transmit the disease to the offspring.
      This mutation can thus be exploited for a rational and efficient selection of
      unequivocally healthy cows for breeding.

PMID- 21740564
TI  - The WRITTEN-HEART study (expressive writing for heart healing): rationale and
      design of a randomized controlled clinical trial of expressive writing in
      coronary patients referred to residential cardiac rehabilitation.
AB  - BACKGROUND: Coronary heart disease (CHD) is typically associated with many
      cardiovascular risk factors (e.g., elevated blood pressure), low health-related
      quality of life, depression, anxiety and psychological stress. Expressive writing
      (EW) has shown beneficial effects on such variables in both people from the
      community and in patients with a variety of chronic illnesses. However, no study
      to date has evaluated the physical and psychological effects of the expressive
      writing procedure on coronary patients referred to cardiac rehabilitation (CR).
      METHODS: The clinical effectiveness of a 2-week disease-related expressive
      writing procedure (writing about one's deepest thoughts and feelings regarding
      the experience with heart disease) compared with the standard writing task
      (writing about one's deepest thoughts and feelings about the most traumatic or
      negative event experienced in the life), a neutral writing condition (writing
      about the facts regarding heart disease and its treatment) and an empty control
      condition will be evaluated in a randomized controlled clinical trial (RCT) with
      repeated follow-up measurements at 3, 6 and 12 months after discharge from CR.
      The primary outcome is health-related quality of life (SF-12). Secondary outcome
      measures are depression (BDI-II), anxiety (BAI) and post-traumatic growth (PTGI).
      Furthermore, the study will explore the moderating effects of coping styles, type
      D personality, perceived emotional support and participants' evaluative ratings
      of the writing interventions on the main experimental effects in order to
      identify sub-groups of patients showing different results. DISCUSSION: The
      WRITTEN-HEART study aims to explore and expand the frontiers of the expressive
      writing research enterprise by investigating the feasibility, safety and clinical
      efficacy of brief and cost-effective expressive writing interventions in patients
      with CHD referred to CR. TRIAL REGISTRATION: ClinicalTrials.gov NCT01253486.

PMID- 21740565
TI  - A comprehensive characterization of the caspase gene family in insects from the
      order Lepidoptera.
AB  - BACKGROUND: The cell suicide pathway of apoptosis is a necessary event in the
      life of multicellular organisms. It is involved in many biological processes
      ranging from development to the immune response. Evolutionarily conserved
      proteases, called caspases, play a central role in regulating apoptosis.
      Reception of death stimuli triggers the activation of initiator caspases, which
      in turn activate the effector caspases. In Lepidoptera, apoptosis is crucial in
      processes such as metamorphosis or defending against baculovirus infection. The
      discovery of p35, a baculovirus protein inhibiting caspase activity, has led to
      the characterization of the first lepidopteran caspase, Sf-Caspase-1. Studies on
      Sf-Caspase-1 mode of activation suggested that apoptosis in Lepidoptera requires
      a cascade of caspase activation, as demonstrated in many other species. RESULTS:
      In order to get insights into this gene family in Lepidoptera, we performed an
      extensive survey of lepidopteran-derived EST datasets. We identified 66 sequences
      distributed among 27 species encoding putative caspases. Phylogenetic analyses
      showed that Lepidoptera possess at least 5 caspases, for which we propose a
      unified nomenclature. According to homology to their Drosophila counterparts and
      their primary structure, we determined that Lep-Caspase-1, -2 and -3 are putative
      effector caspases, whereas Lep-Caspase-5 and -6 are putative initiators. The
      likely function of Lep-Caspase-4 remains unclear. Lep-Caspase-2 is absent from
      the silkworm genome and appears to be noctuid-specific, and to have arisen from a
      tandem duplication of the Caspase-1 gene. In the tobacco hawkmoth, 3 distinct
      transcripts encoding putative Caspase-4 were identified, suggesting at least 2
      duplication events in this species. CONCLUSIONS: The basic repertoire of five
      major types of caspases shared among Lepidoptera seems to be smaller than for
      most other groups studied to date, but gene duplication still plays a role in
      lineage-specific increases in diversity, just as in Diptera and mammals.

PMID- 21740566
TI  - Human papillomavirus serologic follow-up response and relationship to survival in
      head and neck cancer: a case-comparison study.
AB  - BACKGROUND: Human papillomavirus high risk (HPV-HR) type 16 is a significant risk
      factor for head and neck cancers (HNC) independent of tobacco and alcohol. The
      purpose of this study was to determine whether antibody levels to the HPV-16
      oncoproteins E6 and E7 measured in sera collected at baseline (BL) prior to
      treatment and at two post-treatment follow-up (FU) visits were associated with
      HNC risk factors or prognosis. METHODS: Presence of antibodies to HPV-16 E6 and
      E7 was evaluated in 109 newly diagnosed HNC cases with BL and FU blood samples,
      using the enzyme-linked immunosorbent assay (ELISA). RESULTS: HPV-16 E6 and/or E7
      seropositive HNC cases were associated with higher risk in younger patients (<=
      55 years), more sexual partners (>= 10), oropharyngeal cancer, worse stage at
      diagnosis, poorer grade, and nodal involvement. Between BL and FU (median = 8.3
      months), there were decreased antibody levels for seropositive E6 (73% vs. 27%, p
      = 0.02) and seropositive E7 patients (65% vs. 35%, p = 0.09) with 5% of BL E6 and
      35% of BL E7 seropositive patients converting to negative status at FU. Overall
      mortality (OM) was significantly worse among BL E6 seronegative patients than
      among BL seropositive patients (40.2% vs.13.6%, p = 0.01). There were no disease
      specific (DS) deaths among BL E6 seropositive vs. 24% in BL E6 seronegative
      patients (p = 0.01). BL E7 seronegative patients also had higher mortality than
      BL seropositive patients (OM: 38.2% vs. 20.0%, p = 0.04; DS: 22.5% vs. 5.6%, p =
      0.07). CONCLUSION: These findings are the first to follow post-treatment OD
      levels of HPV-16 E6 and E7 in HNC and suggest that these HPV antibodies may be
      potential prognostic markers of survival in HNC patients.

PMID- 21740567
TI  - Chronic pain among homeless persons: characteristics, treatment, and barriers to
      management.
AB  - BACKGROUND: Little information is available on the problem of chronic pain among
      homeless individuals. This study aimed to describe the characteristics of and
      treatments for chronic pain, barriers to pain management, concurrent medical
      conditions, and substance use among a representative sample of homeless single
      adult shelter users who experience chronic pain in Toronto, Canada. METHODS:
      Participants were randomly selected at shelters for single homeless adults
      between September 2007 and February 2008 and screened for chronic pain, defined
      as having pain in the body for >= 3 months or receiving treatment for pain that
      started >= 3 months ago. Cross-sectional surveys obtained information on
      demographic characteristics, characteristics of and treatments for chronic pain,
      barriers to pain management, concurrent medical conditions, and substance use.
      Whenever possible, participants' physicians were also interviewed. RESULTS: Among
      152 homeless participants who experienced chronic pain, 11 (8%) were classified
      as Chronic Pain Grade I (low disability-low intensity), 47 (32%) as Grade II (low
      disability-high intensity), 34 (23%) as Grade III (high disability-moderately
      limiting), and 54 (37%) as Grade IV (high disability-severely limiting). The most
      common self-reported barriers to pain management were stress of shelter life,
      inability to afford prescription medications, and poor sleeping conditions.
      Participants reported using over-the-counter medications (48%), street drugs
      (46%), prescribed medications (43%), and alcohol (29%) to treat their pain. Of
      the 61 interviewed physicians, only 51% reported treating the patient's pain. The
      most common physician-reported difficulties with pain management were reluctance
      to prescribe narcotics due to the patient's history of substance abuse,
      psychiatric comorbidities, frequently missed appointments, and difficulty getting
      the patient to take medications correctly. CONCLUSIONS: Clinicians who provide
      healthcare for homeless people should screen for chronic pain and discuss
      barriers to effective pain management with their patients.

PMID- 21740568
TI  - Representation of multiplication facts--evidence for partial verbal coding.
AB  - BACKGROUND: The current view in numerical cognition research is that
      multiplication facts are stored and retrieved in a phonological code. Consistent
      with this view, it was found that multiplication could be impaired by a
      phonological but not by a visuo-spatial loading task. However, because the
      authors used an active production task, it remained unclear whether concurrent
      articulation impaired either access to multiplication facts or their retrieval.
      METHODS: In the current study, we investigated the influence of concurrent
      articulation on multiplication fact knowledge without active production of
      multiplication results. RESULTS: In a number bisection task, number triplets,
      which are part of a multiplication table, were classified faster as being
      correctly bisected than other triplets. Interestingly, concurrent articulation
      led to a relative slowing of the multiplicative triplets which reduced the
      multiplicativity effect. CONCLUSIONS: This result indicates that concurrent
      articulation modulates access to phonologically stored multiplication facts and
      corroborates the notion of multiplication facts being represented in an at least
      partially verbal code.

PMID- 21740569
TI  - Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium
      ATPase lengthens the period of hepatic clock gene Per1.
AB  - BACKGROUND: The role played by calcium as a regulator of circadian rhythms is not
      well understood. The effect of the pharmacological inhibition of the ryanodine
      receptor (RyR), inositol 1,4,5-trisphosphate receptor (IP3R), and endoplasmic
      reticulum Ca2+-ATPase (SERCA), as well as the intracellular Ca2+-chelator BAPTA
      AM was explored on the 24-h rhythmicity of the liver-clock protein PER1 in an
      experimental model of circadian synchronization by light and restricted-feeding
      schedules. METHODS: Liver explants from Period1-luciferase (Per1-luc) transgenic
      rats with either free food access or with a restricted meal schedule were treated
      for several days with drugs to inhibit the activity of IP3Rs (2-APB), RyRs
      (ryanodine), or SERCA (thapsigargin) as well as to suppress intracellular calcium
      fluctuations (BAPTA-AM). The period of Per1-luc expression was measured during
      and after drug administration. RESULTS: Liver explants from rats fed ad libitum
      showed a lengthened period in response to all the drugs tested. The
      pharmacological treatments of the explants from meal-entrained rats induced the
      same pattern, with the exception of the ryanodine treatment which, unexpectedly,
      did not modify the Per1-luc period. All effects associated with drug application
      were reversed after washout, indicating that none of the pharmacological
      treatments was toxic to the liver cultures. CONCLUSIONS: Our data suggest that
      Ca2+ mobilized from internal deposits modulates the molecular circadian clock in
      the liver of rats entrained by light and by restricted meal access.

PMID- 21740570
TI  - Comparative study of the efficacy and tolerability of dihydroartemisinin
      piperaquine-trimethoprim versus artemether-lumefantrine in the treatment of
      uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal.
AB  - BACKGROUND: The ACT recommended by WHO is very effective and well-tolerated.
      However, these combinations need to be administered for three days, which may
      limit adherence to treatment.The combination of dihydroartemisinin-piperaquine
      phosphate-trimethoprim (Artecom(r), Odypharm Ltd), which involves treatment over
      two days, appears to be a good alternative, particularly in malaria-endemic
      areas. This study intends to compare the efficacy and tolerability of the
      combination dihydroartemisinin-piperaquine phosphate-trimethoprim (DPT) versus
      artemether-lumefantrine (AL) in the treatment of uncomplicated Plasmodium
      falciparum malaria in Cameroon, Ivory Coast and Senegal. METHODS: This was a
      randomized, controlled, open-label clinical trial with a 28-day follow-up period
      comparing DPT to AL as the reference drug. The study involved patients of at
      least two years of age, suffering from acute, uncomplicated Plasmodium falciparum
      malaria with fever. The WHO 2003 protocol was used. RESULTS: A total of 418
      patients were included in the study and divided into two treatment groups: 212 in
      the DPT group and 206 in the AL group. The data analysis involved the 403
      subjects who correctly followed the protocol (per protocol analysis), i.e. 206
      (51.1%) in the DPT group and 197 (48.9%) in the AL group. The recovery rate at
      D14 was 100% in both treatment groups. The recovery rate at D28 was 99% in the
      DPT and AL groups before and after PCR results with one-sided 97.5% Confidence
      Interval of the rates difference > -1.90%. More than 96% of patients who received
      DPT were apyrexial 48 hours after treatment compared to 83.5% in the AL group (p
      < 0.001). More than 95% of the people in the DPT group had a parasite clearance
      time of 48 hours or less compared to approximately 90% in the AL group (p =
      0.023). Both drugs were well tolerated. No serious adverse events were reported
      during the follow-up period. All of the adverse events observed were minor and
      did not result in the treatment being stopped in either treatment group. The main
      minor adverse events reported were vomiting, abdominal pain and pruritus.
      CONCLUSION: The overall efficacy and tolerability of DPT are similar to those of
      AL. The ease of taking DPT and its short treatment course (two days) may help to
      improve adherence to treatment. Taken together, these findings make this
      medicinal product a treatment of choice for the effective management of malaria
      in Africa.

PMID- 21740571
TI  - Neighborhood fast food restaurants and fast food consumption: a national study.
AB  - BACKGROUND: Recent studies suggest that neighborhood fast food restaurant
      availability is related to greater obesity, yet few studies have investigated
      whether neighborhood fast food restaurant availability promotes fast food
      consumption. Our aim was to estimate the effect of neighborhood fast food
      availability on frequency of fast food consumption in a national sample of young
      adults, a population at high risk for obesity. METHODS: We used national data
      from U.S. young adults enrolled in wave III (2001-02; ages 18-28) of the National
      Longitudinal Study of Adolescent Health (n = 13,150). Urbanicity-stratified
      multivariate negative binomial regression models were used to examine cross
      sectional associations between neighborhood fast food availability and individual
      level self-reported fast food consumption frequency, controlling for individual
      and neighborhood characteristics. RESULTS: In adjusted analysis, fast food
      availability was not associated with weekly frequency of fast food consumption in
      non-urban or low- or high-density urban areas. CONCLUSIONS: Policies aiming to
      reduce neighborhood availability as a means to reduce fast food consumption among
      young adults may be unsuccessful. Consideration of fast food outlets near school
      or workplace locations, factors specific to more or less urban settings, and the
      role of individual lifestyle attitudes and preferences are needed in future
      research.

PMID- 21740572
TI  - The evolutionary history of the catenin gene family during metazoan evolution.
AB  - BACKGROUND: Catenin is a gene family composed of three subfamilies; p120, beta
      and alpha. Beta and p120 are homologous subfamilies based on sequence and
      structural comparisons, and are members of the armadillo repeat protein
      superfamily. Alpha does not appear to be homologous to either beta or p120 based
      on the lack of sequence and structural similarity, and the alpha subfamily
      belongs to the vinculin superfamily. Catenins link the transmembrane protein
      cadherin to the cytoskeleton and thus function in cell-cell adhesion. To date,
      only the beta subfamily has been evolutionarily analyzed and experimentally
      studied for its functions in signaling pathways, development and human diseases
      such as cancer. We present a detailed evolutionary study of the whole catenin
      family to provide a better understanding of how this family has evolved in
      metazoans, and by extension, the evolution of cell-cell adhesion. RESULTS: All
      three catenin subfamilies have been detected in metazoans used in the present
      study by searching public databases and applying species-specific BLAST searches.
      Two monophyletic clades are formed between beta and p120 subfamilies using
      Bayesian phylogenetic inference. Phylogenetic analyses also reveal an array of
      duplication events throughout metazoan history. Furthermore, numerous annotation
      issues for the catenin family have been detected by our computational analyses.
      CONCLUSIONS: Delta2/ARVCF catenin in the p120 subfamily, beta catenin in the beta
      subfamily, and alpha2 catenin in the alpha subfamily are present in all metazoans
      analyzed. This implies that the last common ancestor of metazoans had these three
      catenin subfamilies. However, not all members within each subfamily were detected
      in all metazoan species. Each subfamily has undergone duplications at different
      levels (species-specific, subphylum-specific or phylum-specific) and to different
      extents (in the case of the number of homologs). Extensive annotation problems
      have been resolved in each of the three catenin subfamilies. This resolution
      provides a more coherent description of catenin evolution.

PMID- 21740573
TI  - Should patents for antiretrovirals be waived in the developing world? Annual
      Varsity Medical Debate--London, 21 January 2011.
AB  - The 2011 Varsity Medical Debate, between Oxford and Cambridge Universities,
      brought students and faculty together to discuss the waiving of patents for
      antiretroviral therapies in the developing world. With an estimated 29.5 million
      infected by Human Immunodeficiency Virus (HIV) in low- and middle-income
      countries and only 5.3 million of those being treated, the effective and
      equitable distribution of anti-retroviral therapy (ART) is an issue of great
      importance. The debate centred around three areas of contention. Firstly, there
      was disagreement about whether patents were the real barrier to the access of
      anti-retroviral therapy in the developing world. Secondly, there were differing
      views on the effectiveness of a patent pool. Thirdly, concerns were raised over
      the impact of waiving patents on research to produce new and better anti retro
      viral drugs.

PMID- 21740574
TI  - A rigid barrier between the heart and sternum protects the heart and lungs
      against rupture during negative pressure wound therapy.
AB  - OBJECTIVES: Right ventricular heart rupture is a devastating complication
      associated with negative pressure wound therapy (NPWT) in cardiac surgery. The
      use of a rigid barrier has been suggested to offer protection against this lethal
      complication, by preventing the heart from being drawn up and damaged by the
      sharp edges of the sternum. The aim of the present study was to investigate
      whether a rigid barrier protects the heart and lungs against injury during NPWT.
      METHODS: Sixteen pigs underwent median sternotomy followed by NPWT at -120 mmHg
      for 24 hours, in the absence (eight pigs) or presence (eight pigs) of a rigid
      plastic disc between the heart and the sternal edges. The macroscopic appearance
      of the heart and lungs was inspected after 12 and 24 hours of NPWT. RESULTS:
      After 24 hours of NPWT at -120 mmHg the area of epicardial petechial bleeding was
      11.90 +/- 1.10 cm2 when no protective disc was used, and 1.15 +/- 0.19 cm2 when
      using the disc (p < 0.001). Heart rupture was observed in three of the eight
      animals treated with NPWT without the disc. Lung rupture was observed in two of
      the animals, and lung contusion and emphysema were seen in all animals treated
      with NPWT without the rigid disc. No injury to the heart or lungs was observed in
      the group of animals treated with NPWT using the rigid disc. CONCLUSION:
      Inserting a rigid barrier between the heart and the sternum edges offers
      protection against heart rupture and lung injury during NPWT.

PMID- 21740575
TI  - Bath Breakfast Project (BBP)--examining the role of extended daily fasting in
      human energy balance and associated health outcomes: study protocol for a
      randomised controlled trial [ISRCTN31521726].
AB  - BACKGROUND: Current guidance regarding the role of daily breakfast in human
      health is largely grounded in cross-sectional observations. However, the causal
      nature of these relationships has not been fully explored and what limited
      information is emerging from controlled laboratory-based experiments appears
      inconsistent with much existing data. Further progress in our understanding
      therefore requires a direct examination of how daily breakfast impacts human
      health under free-living conditions. METHODS/DESIGN: The Bath Breakfast Project
      (BBP) is a randomised controlled trial comparing the effects of daily breakfast
      consumption relative to extended fasting on energy balance and human health.
      Approximately 70 men and women will undergo extensive laboratory-based
      assessments of their acute metabolic responses under fasted and post-prandial
      conditions, to include: resting metabolic rate, substrate oxidation, dietary
      induced thermogenesis and systemic concentrations of key metabolites/hormones.
      Physiological and psychological indices of appetite will also be monitored both
      over the first few hours of the day (i.e. whether fed or fasted) and also
      following a standardised test lunch used to assess voluntary energy intake under
      controlled conditions. Baseline measurements of participants' anthropometric
      characteristics (e.g. DEXA) will be recorded prior to intervention, along with an
      oral glucose tolerance test and acquisition of adipose tissue samples to
      determine expression of key genes and estimates of tissue-specific insulin
      action. Participants will then be randomly assigned either to a group prescribed
      an energy intake of >=3000 kJ before 1100 each day or a group to extend their
      overnight fast by abstaining from ingestion of energy-providing nutrients until
      1200 each day, with all laboratory-based measurements followed-up 6 weeks later.
      Free-living assessments of energy intake (via direct weighed food diaries) and
      energy expenditure (via combined heart-rate/accelerometry) will be made during
      the first and last week of intervention, with continuous glucose monitors worn
      both to document chronic glycaemic responses to the intervention and to verify
      compliance.

PMID- 21740576
TI  - Differences in lateral gene transfer in hypersaline versus thermal environments.
AB  - BACKGROUND: The role of lateral gene transfer (LGT) in the evolution of
      microorganisms is only beginning to be understood. While most LGT events occur
      between closely related individuals, inter-phylum and inter-domain LGT events are
      not uncommon. These distant transfer events offer potentially greater fitness
      advantages and it is for this reason that these "long distance" LGT events may
      have significantly impacted the evolution of microbes. One mechanism driving
      distant LGT events is microbial transformation. Theoretically, transformative
      events can occur between any two species provided that the DNA of one enters the
      habitat of the other. Two categories of microorganisms that are well-known for
      LGT are the thermophiles and halophiles. RESULTS: We identified potential inter
      class LGT events into both a thermophilic class of Archaea (Thermoprotei) and a
      halophilic class of Archaea (Halobacteria). We then categorized these LGT genes
      as originating in thermophiles and halophiles respectively. While more than 68%
      of transfer events into Thermoprotei taxa originated in other thermophiles, less
      than 11% of transfer events into Halobacteria taxa originated in other
      halophiles. CONCLUSIONS: Our results suggest that there is a fundamental
      difference between LGT in thermophiles and halophiles. We theorize that the
      difference lies in the different natures of the environments. While DNA degrades
      rapidly in thermal environments due to temperature-driven denaturization,
      hypersaline environments are adept at preserving DNA. Furthermore, most
      hypersaline environments, as topographical minima, are natural collectors of
      cellular debris. Thus halophiles would in theory be exposed to a greater
      diversity and quantity of extracellular DNA than thermophiles.

PMID- 21740577
TI  - Common polymorphisms in human lysyl oxidase genes are not associated with the
      adolescent idiopathic scoliosis phenotype.
AB  - BACKGROUND: Although adolescent idiopathic scoliosis affects approximately 3% of
      adolescents, the genetic contributions have proven difficult to identify. Work in
      model organisms, including zebrafish, chickens, and mice, has implicated the
      lysyl oxidase family of enzymes in the development of scoliosis. We hypothesized
      that common polymorphisms in the five human lysyl oxidase genes (LOX, LOXL1,
      LOXL2, LOXL3, and LOXL4) may be associated with the phenotype of adolescent
      idiopathic scoliosis. METHODS: This was a case-control genetic association study.
      A total of 112 coding and tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 were
      genotyped in a discovery cohort of 138 cases and 411 controls. Genotypes were
      tested for association with adolescent idiopathic scoliosis by logistic
      regression with a two degree of freedom genotypic model and gender as a
      covariate. Fourteen SNPs with p < 0.1 in the discovery phase were genotyped in an
      independent replication cohort of 400 cases and 506 controls. RESULTS: No
      evidence for significant association was found between coding or tag SNPs in LOX,
      LOXL1, LOXL2, LOXL3, and LOXL4 and the phenotype of adolescent idiopathic
      scoliosis. CONCLUSIONS: Despite suggestive evidence in model organisms, common
      variants and known coding SNPs in the five human lysyl oxidase genes do not
      confer increased genotypic risk for adolescent idiopathic scoliosis. The above
      methodology does not address rare variants or individually private mutations in
      these genes, and future research may focus on this area.

PMID- 21740578
TI  - The IDvIP trial: a two-centre randomised double-blind controlled trial comparing
      intramuscular diamorphine and intramuscular pethidine for labour analgesia.
AB  - BACKGROUND: Intramuscular pethidine is routinely used throughout the UK for
      labour analgesia. Studies have suggested that pethidine provides little pain
      relief in labour and has a number of side effects affecting mother and neonate.
      It can cause nausea, vomiting and dysphoria in mothers and can cause reduced
      fetal heart rate variability and accelerations. Neonatal effects include
      respiratory depression and impaired feeding. There are few large studies
      comparing the relative side effects and efficacy of different opioids in labour.
      A small trial comparing intramuscular pethidine with diamorphine, showed
      diamorphine to have some benefits over pethidine when used for labour analgesia
      but the study did not investigate the adverse effects of either opioid. METHODS:
      The Intramuscular Diamorphine versus Intramuscular Pethidine (IDvIP) trial is a
      randomised double-blind two centre controlled trial comparing intramuscular
      diamorphine and pethidine regarding their analgesic efficacy in labour and their
      side effects in mother, fetus and neonate. Information about the trial will be
      provided to women in the antenatal period or in early labour. Consent and
      recruitment to the trial will be obtained when the mother requests opioid
      analgesia. The sample size requirement is 406 women with data on primary
      outcomes. The maternal primary outcomes are pain relief during the first 3 hours
      after trial analgesia and specifically pain relief after 60 minutes. The neonatal
      primary outcomes are need for resuscitation and Apgar Score <7 at 1 minute. The
      secondary outcomes are an additional measure of pain relief, maternal sedation,
      nausea and vomiting, maternal oxygen saturation, satisfaction with analgesia,
      whether method of analgesia would be used again, use of Entonox, umbilical
      arterial and venous pH, fetal heart rate, meconium staining, time from delivery
      to first breath, Apgar scores at 5 mins, naloxone requirement, transfer to
      neonatal intensive care unit, neonatal haemoglobin oxygen saturation at 30, 60,
      90, and 120 mins after delivery, and neonatal sedation and feeding behaviour
      during first 2 hours. DISCUSSION: If the trial demonstrates that diamorphine
      provides better analgesia with fewer side effects in mother and neonate this
      could lead to a change in national practice and result in diamorphine becoming
      the preferred intramuscular opioid for analgesia in labour. TRIAL REGISTRATION:
      ISRCTN14898678Eudra No: 2006-003250-18, REC Reference No: 06/Q1702/95, MHRA
      Authorisation No: 1443/0001/001-0001, NIHR UKCRN reference 6895, RfPB grant PB-PG
      0407-13170_IR5.

PMID- 21740579
TI  - Conference on Neuroscience and Pragmatism: Productive Prospects.
AB  - The conference "Neuroscience and Pragmatism: Productive Prospects" was held on
      June 10, 2011 at the Potomac Institute for Policy Studies in Arlington, Virginia.

PMID- 21740580
TI  - Operational challenges in managing Isoniazid Preventive Therapy in child
      contacts: a high-burden setting perspective.
AB  - BACKGROUND: The study was conducted at a high TB-HIV burden primary health
      community clinic in Cape Town, South Africa. We describe the management of
      children under five years of age in household contact with a smear and/or culture
      positive adult TB case. METHODS: This study was a record review of routinely
      collected programme data. RESULTS: A total of 1094 adult TB case folders were
      reviewed. From all identified contacts, 149 children should have received IPT
      based on local guidelines; in only 2/149 IPT was initiated. Management of child
      contacts of sputum smear and/or culture-positive compared to sputum-negative TB
      patients were similar. CONCLUSIONS: IPT delivery to children remains an
      operational challenge, especially in high TB-HIV burden communities. A tool to
      improve IPT management and targeting sputum smear and/or culture-positive TB
      child contacts may overcome some of these challenges and should be developed and
      piloted in such settings.

PMID- 21740581
TI  - Summit on cell therapy for cancer: The importance of the interaction of multiple
      disciplines to advance clinical therapy.
AB  - The field of cellular therapy of cancer is moving quickly and the issues involved
      with its advancement are complex and wide ranging. The growing clinical
      applications and success of adoptive cellular therapy of cancer has been due to
      the rapid evolution of immunology, cancer biology, gene therapy and stem cell
      biology and the translation of advances in these fields from the research
      laboratory to the clinic. The continued development of this field is dependent on
      the exchange of ideas across these diverse disciplines, the testing of new ideas
      in the research laboratory and in animal models, the development of new cellular
      therapies and GMP methods to produce these therapies, and the testing of new
      adoptive cell therapies in clinical trials. The Summit on Cell Therapy for Cancer
      to held on November 1 and 2, 2011 at the National Institutes of Health (NIH)
      campus will include a mix of perspectives, concepts and ideas related to adoptive
      cellular therapy that are not normally presented together at any single meeting.
      This novel assembly will generate new ideas and new collaborations and possibly
      increase the rate of advancement of this field.

PMID- 21740582
TI  - Evaluating RNAlater(r) as a preservative for using near-infrared spectroscopy to
      predict Anopheles gambiae age and species.
AB  - BACKGROUND: Mosquito age and species identification is a crucial determinant of
      the efficacy of vector control programmes. Near-infrared spectroscopy (NIRS) has
      previously been applied successfully to rapidly, non-destructively, and
      simultaneously determine the age and species of freshly anesthetized African
      malaria vectors from the Anopheles gambiae s.l. species complex: An. gambiae s.
      s. and Anopheles arabiensis. However, this has only been achieved on freshly
      collected specimens and future applications will require samples to be preserved
      between field collections and scanning by NIRS. In this study, a sample
      preservation method (RNAlater((r))) was evaluated for mosquito age and species
      identification by NIRS against scans of fresh samples. METHODS: Two strains of
      An. gambiae s.s. (CDC and G3) and two strains of An. arabiensis (Dongola, KGB)
      were reared in the laboratory while the third strain of An. arabiensis (Ifakara)
      was reared in a semi-field system. All mosquitoes were scanned when fresh and
      rescanned after preservation in RNAlater((r)) for several weeks. Age and species
      identification was determined using a cross-validation. RESULTS: The mean
      accuracy obtained for predicting the age of young (<7 days) or old (>= 7 days) of
      all fresh (n = 633) and all preserved (n = 691) mosquito samples using the cross
      validation technique was 83% and 90%, respectively. For species identification,
      accuracies were 82% for fresh against 80% for RNAlater((r)) preserved. For both
      analyses, preserving mosquitoes in RNAlater((r)) was associated with a highly
      significant reduction in the likelihood of a misclassification of mosquitoes as
      young or old using NIRS. Important to note is that the costs for preserving
      mosquito specimens with RNAlater((r)) ranges from 3-13 cents per insect depending
      on the size of the tube used and the number of specimens pooled in one tube.
      CONCLUSION: RNAlater((r)) can be used to preserve mosquitoes for subsequent
      scanning and analysis by NIRS to determine their age and species with minimal
      costs and with accuracy similar to that achieved from fresh insects. Cold storage
      availability allows samples to be stored longer than a week after field
      collection. Further study to develop robust calibrations applicable to other
      strains from diverse ecological settings is recommended.

PMID- 21740583
TI  - Anti-inflammatory effects of Chinese medicinal herbs on cerebral ischemia.
AB  - Recent studies have demonstrated the importance of anti-inflammation, including
      cellular immunity, inflammatory mediators, reactive oxygen species, nitric oxide
      and several transcriptional factors, in the treatment of cerebral ischemia. This
      article reviews the roles of Chinese medicinal herbs as well as their ingredients
      in the inflammatory cascade induced by cerebral ischemia. Chinese medicinal herbs
      exert neuroprotective effects on cerebral ischemia. The effects include
      inhibiting the activation of microglia, decreasing levels of adhesion molecules
      such as intracellular adhesion molecule-1, attenuating expression of pro
      inflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha,
      reducing inducible nitric oxide synthase and reactive oxygen species, and
      regulating transcription factors such as nuclear factor-kappaB.

PMID- 21740584
TI  - Hospital based palliative care in sub-Saharan Africa; a six month review from
      Malawi.
AB  - BACKGROUND: The World Health Organisation recognises the importance of palliative
      care in an African setting. Despite this services are often patchy and
      inconsistent, and many operate at health centre and/or community level. Few
      reports from hospital based palliative care services in sub-Saharan Africa exist
      in the current literature. As part of its activities Tiyanjane Clinic has been
      providing hospital based palliative care to patients at Queen Elizabeth Central
      Hospital, a large government tertiary referral institution, in the Southern
      region of Malawi since 2003, caring for patients with HIV, cancer and other non
      malignant palliative diagnoses. METHODS: A retrospective review of case notes for
      all in-patients seen by Tiyanjane Clinic over a six month period (April-Sept
      2009) was undertaken. RESULTS: A total of 177 patients were seen, for whom 137
      case notes were available (77%). 58% of patients were male, 42% female. The
      average age of patients was 39.1 years (range 15-92 years). 54% of patients were
      HIV positive, with 34% on ARV drugs at the time of care. 42% of patients had HIV
      related diagnoses, including AIDS defining malignancies, 48% had (non AIDS
      related) cancers and 9% had other palliative diagnoses. The mean age of patients
      with HIV related diagnoses was 34 years, for cancer patients it was 48 years.
      Pain was the most commonly reported symptom (74%), with 56% of patients requiring
      oral morphine. The mean daily dose of morphine was 30 mg/day (range 9-100 mg).
      65% of patients were discharged home, 26% of patients died during admission.
      CONCLUSIONS: The palliative care population in this setting is relatively young,
      especially among patients with HIV related diagnoses. HIV and cancer are the main
      diagnostic groups. Pain is the most commonly reported symptom, with oral morphine
      frequently required. Health workers require access to and knowledge of oral
      morphine in order to provide appropriate assistance to patients under their care.

PMID- 21740585
TI  - Etiopathogenesis of Burkitt's lymphoma: a lesson from a BL-like in CD1 mouse
      immune to Plasmodium yoelii yoelii.
AB  - INTRODUCTION: There is a jaw cancer that develops in children five to eight years
      old in holoendemic malaria regions of Africa, associated to malaria and Epstein
      Barr virus infections (EBV). This malignancy is known as endemic Burkitt's
      lymphoma, and histopatologically is characterized by a starry sky appearance. To
      date, no histopathologic expression of Burkitt's lymphoma has been reported in
      non-genetically manipulated experimental animals. The purpose of the study is to
      describe the case of a mouse immune to Plasmodium yoelii yoelii (Pyy) that
      developed a Burkitt's lymphoma-like neoplasm after repeated malaria infections.
      RESULTS: Immune mouse 10 (IM-10) developed neoplasms at eight months of age,
      after receiving three Pyy inoculations. At autopsy eight subcutaneous tumors were
      found of which the right iliac fosse tumor perforated the abdominal wall and
      invaded the colon. The histopathologic study showed that all neoplasms were
      malignant lymphomas of large non-cleaved cells also compatible with variants or
      previous states of development of a Burkitt's lymphoma-like. The thymus, however,
      showed a typical starry sky Burkitt's lymphoma-like neoplasm. CONCLUSIONS:
      Neoplasm development in CD1 mouse is associated to both, immunity against malaria
      and continuous antigenic stimulation with living parasites.It is the first
      observation of a histopathologically expressed Human Burkitt's lymphoma-like
      neoplasm in a non-genetically manipulated mouse.Chronic immune response
      associated to neoplasms development could probably be not an exclusive expression
      of malaria-host interaction but, it could be a pattern that can bee applied also
      to other agent-host interactions such as host-bacteria, fungus, virus and other
      parasites.

PMID- 21740586
TI  - Investigation on two abnormal phenomena about thermal conductivity enhancement of
      BN/EG nanofluids.
AB  - The thermal conductivity of boron nitride/ethylene glycol (BN/EG) nanofluids was
      investigated by transient hot-wire method and two abnormal phenomena was
      reported. One is the abnormal higher thermal conductivity enhancement for BN/EG
      nanofluids at very low-volume fraction of particles, and the other is the thermal
      conductivity enhancement of BN/EG nanofluids synthesized with large BN
      nanoparticles (140 nm) which is higher than that synthesized with small BN
      nanoparticles (70 nm). The chain-like loose aggregation of nanoparticles is
      responsible for the abnormal increment of thermal conductivity enhancement for
      the BN/EG nanofluids at very low particles volume fraction. And the difference in
      specific surface area and aspect ratio of BN nanoparticles may be the main
      reasons for the abnormal difference between thermal conductivity enhancements for
      BN/EG nanofluids prepared with 140- and 70-nm BN nanoparticles, respectively.

PMID- 21740587
TI  - Giant secreting adrenal myelolipoma in a man: a case report.
AB  - INTRODUCTION: Adrenal myelolipoma is a rare, benign neoplasm that is usually
      asymptomatic, unilateral and nonsecreting. It develops within the adrenal gland
      and is composed of mature adipose tissue with elements of the hematopoietic
      series. We describe the case of what is, to the best of our knowledge, one of the
      largest secreting adrenal myelolipomas reported in the literature. CASE
      PRESENTATION: A 52-year-old Caucasian man of medium build who had had moderate
      hypertension for three years presented to our hospital. He had no other
      significant symptoms. His hypertension was pharmacologically treated. He came to
      our hospital to undergo abdominal ultrasonography during a clinical checkup. The
      ultrasound scan showed the presence of a voluminous hyperechoic mass interposed
      between the spleen and the left kidney. It was reported as a myelolipoma of the
      left kidney on the basis of its structural characteristics and position. Computed
      tomography confirmed our diagnosis. All preoperative biochemical tests were
      normal, with the exception of high serum cortisol, which was being overproduced
      by the lesion and was probably responsible for the patient's hypertension. He
      underwent successful surgery, and his postoperative course was uneventful. The
      pathologic examination of the lesion confirmed the diagnosis of adrenal
      myelolipoma. The patient's blood pressure returned to within the normal range.
      CONCLUSIONS: The "incidental" discovery of an adrenal mass requires careful
      diagnostic study to plan adequate therapeutic management. Both of the primary
      investigations at our disposal, ultrasound and blood tests (adrenal hormones),
      helped in rendering the diagnosis and allowed us to move toward the most
      appropriate treatment, taking into account the size of the tumor and its probable
      hormonal production.

PMID- 21740588
TI  - Post-infection immunocomplex glomerulonephritis and Legionnaires' disease in a
      patient with adult Still's disease during treatment with interleukin 1 receptor
      antagonist anakinra: a case report.
AB  - INTRODUCTION: Legionellosis is a systemic disease that primarily affects the
      lungs. However, dysfunction in many organ systems, including the kidneys, has
      also been described. There are only a few reported cases of renal dysfunction in
      patients with legionellosis. CASE PRESENTATION: A 27-year-old Caucasian woman
      with known adult Still's disease was admitted to our hospital for community
      acquired pneumonia, due to Legionella infection, with acute renal failure.
      Although her respiratory symptoms responded well to antibiotic treatment, her
      renal function worsened, with severe proteinuria and edema. A renal biopsy showed
      extracapillary and endocapillary proliferative glomerulonephritis with
      accompanying chronic and acute interstitial nephritis. This was consistent with a
      post-infection immunocomplex glomerulonephritis. After initiation of steroid
      therapy, her renal function improved. Additionally, therapy with diuretics and an
      angiotensin-converting enzyme inhibitor was initiated because of persistent
      proteinuria. Under this treatment regimen, her severe edema and proteinuria
      disappeared. CONCLUSION: To the best of our knowledge, there is only a handful of
      reported cases of post-infection glomerulonephritis with a nephrotic syndrome in
      a patient with legionellosis. Our findings suggest that, in patients with
      Legionnaires' disease with renal failure, post-infection immunocomplex
      glomerulonephritis should be considered and steroid therapy may be an effective
      modality to treat the renal complication.

PMID- 21740589
TI  - Soil transmitted helminths and schistosoma mansoni infections among school
      children in Zarima town, northwest Ethiopia.
AB  - BACKGROUND: In Ethiopia, because of low quality drinking water supply and latrine
      coverage, helminths infections are the second most predominant causes of
      outpatient morbidity. Indeed, there is a scarcity of information on the
      prevalence of soil transmitted helminths and Schistosomiasis in Ethiopia, special
      in study area. Therefore, the aim of this study was to determine the prevalence
      and associated risk factors of soil transmitted helminths and intestinal
      Schistosomiasis. METHODS: Cross-sectional study was conducted among 319 school
      children of Zarima town from April 1 to May 25, 2009. A pre-tested structured
      questionnaire was used to collect socio-demographic data and possible risk
      factors exposure. Early morning stool samples were collected and a Kato Katz semi
      concentration technique was used to examine and count parasitic load by compound
      light microscope. Data entry and analysis was done using SPSS-15 version and p
      value < 0.05 considered statistically significant. RESULTS: Out of 319 study
      subjects, 263 (82.4%) of the study participants infected with one or more
      parasites. From soil transmitted helminths, Ascaris lumbricoides was the
      predominant isolate (22%) followed by Hookworms (19%) and Trichuris trichiura
      (2.5%). Schistosoma mansoni was also isolated in 37.9% of the study participants.
      Hookworm and S. mansoni infections showed statistically significant associations
      with shoe wearing and swimming habit of school children, respectively.
      CONCLUSION: Prevalence of soil transmitted helminths (STH) and S.mansoni was high
      and the diseases were still major health problem in the study area which alerts
      public health intervention as soon as possible.

PMID- 21740590
TI  - Cost-analysis of XELOX and FOLFOX4 for treatment of colorectal cancer to assist
      decision-making on reimbursement.
AB  - BACKGROUND: XELOX (capecitabine + oxaliplatin) and FOLFOX 4 (5-FU + folinic acid
      + oxaliplatin) have shown similar improvements in survival in patients with
      metastatic colorectal cancer (MCRC). A US cost-minimization study found that the
      two regimens had similar costs from a healthcare provider perspective but XELOX
      had lower costs than FOLFOX4 from a societal perspective, while a Japanese cost
      effectiveness study found XELOX had superior cost-effectiveness. This study
      compared the costs of XELOX and FOLFOX4 in patients with MCRC recently treated in
      two oncology departments in Hong Kong. METHODS: Cost data were collected from the
      medical records of 60 consecutive patients (30 received XELOX and 30 FOLFOX4)
      from two hospitals. Drug costs, outpatient visits, hospital days and
      investigations were recorded and expressed as cost per patient from the
      healthcare provider perspective. Estimated travel and time costs were included in
      a societal perspective analysis. All costs were classed as either scheduled
      (associated with planned chemotherapy and follow-up) or unscheduled (unplanned
      visits or admissions and associated tests and medicines). Costs were based on
      government and hospital sources and expressed in US dollars (US$). RESULTS: XELOX
      patients received an average of 7.3 chemotherapy cycles (of the 8 planned cycles)
      and FOLFOX4 patients received 9.2 cycles (of the 12 planned cycles). The
      scheduled cost per patient per cycle was $2,046 for XELOX and $2,152 for FOLFOX4,
      while the unscheduled cost was $240 and $421, respectively. Total treatment cost
      per patient was $16,609 for XELOX and $23,672 for FOLFOX4; the total cost for
      FOLFOX4 was 37% greater than that of XELOX. The addition of the societal costs
      increased the total treatment cost per patient to $17,836 for XELOX and $27,455
      for FOLFOX4. Sensitivity analyses showed XELOX was still less costly than FOLFOX4
      when using full drug regimen costs, incorporating data from a US model with costs
      and adverse event data from their clinical trial and with the removal of
      oxaliplatin from both treatment arms. Capecitabine would have to cost around four
      times its present price in Hong Kong for the total resource cost of treatment
      with XELOX to equal that of FOLFOX4. CONCLUSION: XELOX costs less than FOLFOX4
      for this patient group with MCRC from both the healthcare provider and societal
      perspectives.

PMID- 21740591
TI  - Recent hospitalization for non-coronary events and use of preventive medications
      for coronary artery disease: an observational cohort study.
AB  - BACKGROUND: High-quality systems have adopted a comprehensive approach to
      preventive care instead of diagnosis or procedure driven care. The current
      emphasis on prescribing medications to prevent complications of coronary artery
      disease (CAD) at discharge following an acute coronary syndrome (ACS) may exclude
      high-risk patients who are hospitalized with conditions other than ACS. METHODS:
      Among a sample of patients with CAD treated at Veterans Affairs medical centers
      between January, 2005 and November, 2006, we investigated whether recent non-ACS
      hospitalization was associated with prescriptions of preventive medications as
      compared with patients recently hospitalized with ACS. RESULTS: Of 13,211
      patients with CAD, 58% received aspirin, 70% beta-blocker, 60% angiotensin
      converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB), and
      65% lipid-lowering therapy. Twenty-five percent of eligible patients were
      receiving all four medications. Having been hospitalized for a non-ACS event in
      the prior 6 months did not substantially affect the adjusted proportion on
      preventive medications. In contrast, among patients hospitalized for ACS in the
      prior 6 months, the adjusted proportion prescribed aspirin was 21% higher (p <
      0.001), beta-blocker was 14% higher (p < 0.001), ACE-I or ARB was 9% higher (p <
      0.001), lipid therapy was 12% higher (p < 0.001), and prescribed all four
      medications was 18% higher (p < 0.001) than among patients hospitalized for ACS
      more than 2 years earlier. CONCLUSIONS: Being hospitalized for a non-ACS
      condition did not appear to influence preventive medication use among patients
      with CAD and represents a missed opportunity to improve patient care. The same
      protocols employed to improve use of preventive medications in patients
      discharged for ACS might be extended to CAD patients discharged for other
      conditions as well.

PMID- 21740592
TI  - Stroke in hereditary hemorrhagic telangiectasia patients. New evidence for
      repeated screening and early treatment of pulmonary vascular malformations: two
      case reports.
AB  - BACKGROUND: Paradoxical embolism due to pulmonary arteriovenous malformations is
      the main mechanism of brain infarction in patients with hereditary hemorrhagic
      telangiectasia. International Guidelines have recently been published to clarify
      the performance of screening tests and the effectiveness of treatment for
      pulmonary arteriovenous malformations. CASE PRESENTATION: We present two cases of
      hereditary hemorrhagic telangiectasia patients of our hospital who experienced an
      acute stroke secondary to paradoxical embolism. CONCLUSIONS: These two cases show
      that the guidelines must be followed to prevent the occurrence of ischemic stroke
      in patients with hereditary hemorrhagic telangiectasia, and that although they
      may be adequate in most cases, there are some patients who need a more
      personalized approach.

PMID- 21740593
TI  - Alcohol consumption in tertiary education students.
AB  - BACKGROUND: Heavy alcohol consumption among adolescents and young adults is an
      issue of significant public concern. With approximately 50% of young people aged
      18-24 attending tertiary education, there is an opportunity within these settings
      to implement programs that target risky drinking. The aim of the current study
      was to survey students and staff within a tertiary education institution to
      investigate patterns of alcohol use, alcohol-related problems, knowledge of
      current National Health and Medical Research Council (NHMRC) guidelines for
      alcohol consumption and intentions to seek help for alcohol problems. METHODS:
      Students of an Australian metropolitan university (with staff as a comparison
      group) participated in a telephone interview. Questions related to knowledge of
      NHMRC guidelines, drinking behaviour, alcohol-related problems and help-seeking
      intentions for alcohol problems. Level of psychological distress was also
      assessed. RESULTS: Of the completed interviews, 774 (65%) were students and 422
      (35%) were staff. While staff were more likely to drink regularly, students were
      more likely to drink heavily. Alcohol consumption was significantly higher in
      students, in males and in those with a history of earlier onset drinking. In most
      cases, alcohol-related problems were more likely to occur in students. The
      majority of students and staff had accurate knowledge of the current NHMRC
      guidelines, but this was not associated with lower levels of risky drinking.
      Psychological distress was associated with patterns of risky drinking in
      students. CONCLUSIONS: Our findings are consistent with previous studies of
      tertiary student populations, and highlight the disconnect between knowledge of
      relevant guidelines and actual behaviour. There is a clear need for interventions
      within tertiary education institutions that promote more effective means of
      coping with psychological distress and improve help-seeking for alcohol problems,
      particularly among young men.

PMID- 21740594
TI  - Effect of Qigong on quality of life: a cross-sectional population-based
      comparison study in Taiwan.
AB  - BACKGROUND: Qigong, similar to Tai Chi Chuan, is beneficial to health. In Taiwan,
      Waitankung, a type of Qigong, is as popular as Tai Chi Chuan. This population
      based comparison study compares the health-related quality of life between people
      practicing Waitankung and their comparable community residents. METHODS: A total
      of 165 individuals practicing Waitankung were matched by age and sex with 660
      general individuals for comparison. Information about health-related quality of
      life, measured by the SF-36, and other basic and health conditions was obtained
      from the questionnaires. This study used the linear mixed-effect regression model
      to examine the association between health-related quality of life and the
      practice of Waitankung. RESULTS: Compared with either sedentary individuals or
      individuals practicing other types of exercise, the Waitankung group scored
      higher for eight and five out of ten SF-36 components, respectively. The
      Waitankung group scored better in general health, vitality, and physical
      component summary compared to individuals participating in other types of
      exercise, even when considering the energy expended by exercise. CONCLUSION: The
      results suggest that Waitankung exercising is significantly associated with
      health-related quality of life. Waitankung may serve as an exercise choice for
      middle-aged and older people to improve overall quality of life.

PMID- 21740595
TI  - Assessment of human cytomegalovirus co-infection in Egyptian chronic HCV
      patients.
AB  - Human cytomegalovirus (HCMV) is the most common cause of severe morbidity and
      mortality in immune- compromised individuals. This study was conducted to
      determine the incidence of HCMV infection in HCV patients who either
      spontaneously cleared the virus or progressed to chronic HCV infection. The study
      included a total of eighty four cases (48 females and 36 males) that were
      referred to blood banks for blood donation with an age range of 18-64 years (mean
      age 37.62 +/- 10.03 years). Hepatitis C virus RNA and HCMV DNA were detected in
      sera by RT-nested PCR and nested PCR respectively in all subjects. Immunoglobulin
      G levels for HCV and HCMV were determined. Besides, IgM antibodies for HCMV
      infection were also determined in subjects' sera. Fifty three out of 84 cases
      (63%) were positive for HCV-RNA while 31 (37%) cases had negative HCV RNA. Forty
      six (87%) and 13 (25%) cases out of 53 HCV RNA positive patients were positive
      for HCMV IgG and IgM antibodies respectively. While 20 of 53 cases (38%) had
      detectable HCMV DNA. To examine the role of HCMV infection in HCV spontaneous
      resolution, two groups of HCV patients, group 1) chronic HCV infection (positive
      HCV RNA and positive IgG antibodies) vs group 2) spontaneous resolution (negative
      HCV RNA and positive IgG antibodies) were compared. The percentages of positive
      CMV IgG and IgM results is higher in chronic HCV patient than those in
      spontaneously cleared HCV patients and the difference is highly statistically
      significant (P value < 0.001). Also, there is a general trend towards elevated
      levels of CMV IgG antibodies in HCV chronic patients than those in spontaneously
      cleared HCV patients (P value < 0.02). HCMV DNA detection in group 1 was more
      than twice the value observed in group 2 (38% vs 14.3%, P value < 0.001).
      Moreover, levels of liver enzymes were significantly higher in HCV RNA positive
      cases co-infected with HCMV DNA than HCMV negative cases (P value < 0.001). The
      results indicate the role of HCMV in the liver pathogenesis. We conclude that
      chronic HCV patients co-infected with HCMV infection can be regarded as high risk
      groups for liver disease progression where they should be monitored for the long
      term outcome of the disease.

PMID- 21740596
TI  - Mental health impairment in underweight women: do body dissatisfaction and eating
      disordered behavior play a role?
AB  - BACKGROUND: We sought to evaluate the hypothesis that mental health impairment in
      underweight women, where this occurs, is due to an association between low body
      weight and elevated levels of body dissatisfaction and/or eating-disordered
      behaviour. METHODS: Subgroups of underweight and normal-weight women recruited
      from a large, general population sample were compared on measures of body
      dissatisfaction, eating-disordered behaviour and mental health. RESULTS:
      Underweight women had significantly greater impairment in mental health than
      normal-weight women, even after controlling for between-group differences in
      demographic characteristics and physical health. However, there was no evidence
      that higher levels of body dissatisfaction or eating-disordered behaviour
      accounted for this difference. Rather, underweight women had significantly lower
      levels of body dissatisfaction and eating-disordered behaviour than normal-weight
      women. CONCLUSIONS: The findings suggest that mental health impairment in
      underweight women, where this occurs, is unlikely to be due to higher levels of
      body dissatisfaction or eating-disordered behaviour. Rather, lower levels of body
      dissatisfaction and eating-disordered behaviour among underweight women may
      counterbalance, to some extent, impairment due to other factors.

PMID- 21740597
TI  - Management of a rare case of arrhythmogenic right ventricular dysplasia in
      pregnancy: a case report.
AB  - INTRODUCTION: Arrhythmogenic right ventricular dysplasia is a heritable disease
      of the heart muscle characterized by fibrofatty degeneration of cardiomyocytes.
      Patients present with ventricular arrhythmias or congestive heart failure, and
      sometimes sudden cardiac death occurs. Prenatal diagnosis has become possible
      with the detection of mutations, but, to the best of our knowledge, no case of
      prenatal diagnosis has been reported previously. There is little information
      about the management of arrhythmogenic right ventricular dysplasia in pregnancy,
      and the preferred mode of delivery is not certain; therefore, we present the case
      of a patient with arrhythmogenic right ventricular dysplasia and discuss the
      prenatal diagnosis, patient management and prognosis in pregnancy. CASE
      PRESENTATION: A 26-year-old Caucasian woman who presented to our hospital with
      heart palpitations was diagnosed with arrhythmogenic right ventricular dysplasia,
      and, after three years of follow up with anti-arrhythmic drugs, she wanted to
      conceive. During pregnancy, she ceased taking her medication. She tolerated
      pregnancy very well but her cardiac symptoms recurred after her 30th week of
      pregnancy. She delivered a baby via cesarean section under general anesthesia in
      her 38th week of pregnancy. She was discharged without any medications and
      continued lactation for six months. CONCLUSION: Patients with mild to moderate
      arrhythmogenic right ventricular dysplasia tolerate pregnancy and breastfeeding
      very well, but patients with end-stage arrhythmogenic right ventricular dysplasia
      should be discouraged from conception.

PMID- 21740598
TI  - Glycoprotein is enough for sindbis virus-derived DNA vector to express
      heterogenous genes.
AB  - To investigate the necessity and potential application of structural genes for
      expressing heterogenous genes from Sindbis virus-derived vector, the DNA-based
      expression vector pVaXJ was constructed by placing the recombinant genome of
      sindbis-like virus XJ-160 under the control of the human cytomegalovirus (CMV)
      promoter of the plasmid pVAX1, in which viral structural genes were replaced by a
      polylinker cassette to allow for insertion of heterologous genes. The defect
      helper plasmids pVaE or pVaC were developed by cloning the gene of glycoprotein
      E3E26KE1 or capsid protein of XJ-160 virus into pVAX1, respectively. The report
      gene cassette pVaXJ-EGFP or pV-Gluc expressing enhanced green fluorescence
      protein (EGFP) or Gaussia luciferase (G.luc) were constructed by cloning EGFP or
      G.luc gene into pVaXJ. EGFP or G.luc was expressed in the BHK-21 cells co
      transfected with report gene cassettes and pVaE at levels that were comparable to
      those produced by report gene cassettes, pVaC and pVaE and were much higher than
      the levels produced by report gene cassette and pVaC, suggesting that
      glycoprotein is enough for Sindbis virus-derived DNA vector to express
      heterogenous genes in host cells. The method of gene expression from Sindbis
      virus-based DNA vector only co-transfected with envelop E gene increase the
      conveniency and the utility of alphavirus-based vector systems in general.

PMID- 21740599
TI  - Multidrug-resistance proteins are weak tumor associated antigens for colorectal
      carcinoma.
AB  - BACKGROUND: Multidrug resistance (MDR) is a clinically, highly relevant
      phenomenon. Under chemotherapy many tumors show an increasing resistance towards
      the applied substance(s) and to a certain extent also towards other agents. An
      important molecular cause of this phenomenon is an increased expression of
      transporter proteins. The functional relationship between high expression levels
      and chemotherapy resistance makes these MDR and MRP (MDR related protein)
      proteins to interesting therapeutic targets. We here wanted to systematically
      analyze, whether these proteins are tumor specific antigens which could be
      targeted immunologically. RESULTS: Using the reverse immunology approach, 30 HLA
      A2.1 restricted MDR and MRP derived peptides (MDP) were selected. Stimulated T
      cell lines grew well and mainly contained activated CD8+ cells. Peptide
      specificity and HLA-A2.1 restriction were proven in IFN-gamma-ELISpot analyses
      and in cytotoxicity tests against MDP loaded target cells for a total of twelve
      peptides derived from MDR-1, MDR-3, MRP-1, MRP-2, MRP-3 and MRP-5. Of note, two
      of these epitopes are shared between MDR-1 and MDR-3 as well as MRP-2 and MRP-3.
      However, comparably weak cytotoxic activities were additionally observed against
      HLA-A2.1+ tumor cells even after upregulation of MDR protein expression by in
      vitro chemotherapy. CONCLUSIONS: Taken together, these data demonstrate that
      human T cells can be sensitised towards MDPs and hence, there is no absolute
      immunological tolerance. However, our data also hint towards rather low
      endogenous tumor cell processing and presentation of MDPs in the context of HLA
      A2.1 molecules. Consequently, we conclude that MDR and MRP proteins must be
      considered as weak tumor specific antigens-at least for colorectal carcinoma.
      Their direct contribution to therapy-failure implies however, that it is worth to
      further pursue this approach.

PMID- 21740600
TI  - Reliability of goniometric measurements in children with cerebral palsy: a
      comparative analysis of universal goniometer and electronic inclinometer. A pilot
      study.
AB  - BACKGROUND: Even though technological progress has provided us with more and more
      sophisticated equipment for making goniometric measurements, the most commonly
      used clinical tools are still the universal goniometer and, to a lesser extent,
      the inclinometer. There is, however, no published study so far that uses an
      inclinometer for measurements in children with cerebral palsy (CP). The objective
      of this study was two-fold: to independently assess the intra and inter-examiner
      reliability for measuring the hip abduction range of motion in children with CP
      using two different instruments, the universal two-axis goniometer and electronic
      inclinometer. A pool of 5 examiners with different levels of experience as
      paediatric physiotherapists participated. The study did not compare both
      instruments because the measurement procedure and the hip position were different
      for each. METHODS: A prospective, observational study of goniometery was carried
      out with 14 lower extremities of 7 children with spastic CP. The inclinometer
      study was carried out with 8 lower extremities of 4 children with spastic CP.
      This study was divided into two independent parts: a study of the reliability of
      the hip abduction range of motion measured with a universal goniometer (hip at 0
      degrees  flexion) and with an electronic inclinometer (hip at 90 degrees 
      flexion). The Intraclass Correlation Coefficient (ICC) was calculated to analyse
      intra and inter-examiner agreement for each instrument. RESULTS: For the
      goniometer, the intra-examiner reliability was excellent (>0.80), while the inter
      examiner reliability was low (0.375 and 0.475). For the inclinometer, both the
      intra-examiner (0.850-0.975) and inter-examiner reliability were excellent (0.965
      and 0.979). CONCLUSIONS: The inter-examiner reliability for goniometric
      measurement of hip abduction in children with CP was low, in keeping with other
      results found in previous publications. The inclinometer has proved to be a
      highly reliable tool for measuring the hip abduction range of motion in children
      with CP, which opens up new possibilities in this field, despite having some
      measurement limitations.

PMID- 21740601
TI  - Diagnosis of kidney damage using novel acute kidney injury biomarkers: assessment
      of kidney function alone is insufficient.
AB  - Acute kidney injury (AKI) is a syndrome that is associated with a major burden of
      morbidity and mortality in a variety of high risk patient populations, many of
      them cared for by intensivists. Following renal transplantation, delayed graft
      function (DGF) caused by severe acute tubular necrosis (ATN), defined by a
      requirement for dialysis during the initial post-transplant week, complicates
      postoperative management, and if prolonged (>14 days), adversely affects
      allograft survival. Neutrophil gelatinase-associated lipocalin (NGAL) and other
      novel biomarkers can detect AKI earlier than serum creatinine, and can predict
      AKI severity in high risk patient populations, including kidney transplant
      recipients. Hollmen and colleagues now demonstrate that elevated urine NGAL in
      deceased kidney donors is a significant risk factor for prolonged post-transplant
      DGF in recipients. These findings have clear implications with regard to
      potentially improved assessment of deceased donor suitability for potential renal
      allograft donation. These findings are also consistent with the growing evidence
      that severe ATN diagnosed by markedly elevated levels of AKI biomarkers is a
      useful predictor of the requirement for acute renal replacement therapy in AKI
      patients.

PMID- 21740602
TI  - Inflammation and wound healing: the role of the macrophage.
AB  - The macrophage is a prominent inflammatory cell in wounds, but its role in
      healing remains incompletely understood. Macrophages have many functions in
      wounds, including host defence, the promotion and resolution of inflammation, the
      removal of apoptotic cells, and the support of cell proliferation and tissue
      restoration following injury. Recent studies suggest that macrophages exist in
      several different phenotypic states within the healing wound and that the
      influence of these cells on each stage of repair varies with the specific
      phenotype. Although the macrophage is beneficial to the repair of normally
      healing wounds, this pleotropic cell type may promote excessive inflammation or
      fibrosis under certain circumstances. Emerging evidence suggests that macrophage
      dysfunction is a component of the pathogenesis of nonhealing and poorly healing
      wounds. As a result of advances in the understanding of this multifunctional
      cell, the macrophage continues to be an attractive therapeutic target, both to
      reduce fibrosis and scarring, and to improve healing of chronic wounds.

PMID- 21740603
TI  - Training parents of overweight children in parenting skills: a 12-month
      evaluation.
AB  - BACKGROUND: The origins of childhood obesity invariably need to be looked at
      within a family context and several reviews have concluded in favour of parental
      involvement in the treatment of paediatric obesity. However, there is little
      consensus on the format, and next to weight outcomes behavioural outcomes also
      merit more attention when assessing program effectiveness. METHOD: In this pilot
      study, a total of 50 families with overweight children (aged 6-12) were randomly
      allocated to a parent-led intervention group (cognitive behavioural training) or
      to a waiting list control group (Study 1). Afterwards, the parents of the
      waitlist control group also followed the intervention. All children were included
      in a follow-up study and were compared with a reference group (Study 2). RESULTS:
      The intervention group as well as the waitlist group (who had not yet received
      treatment) showed a decrease in adjusted BMI over a 6-month period, although the
      decrease was only significant for the intervention group (Study 1). All children
      showed a decrease of 7% in adjusted BMI from pre to one-year follow-up
      measurement (Study 2), while the reference group showed an increase in adjusted
      BMI over that period. Parents reported significant positive changes in children's
      eating behaviour and a significant positive increase in familial health
      principles. CONCLUSIONS: Weight and behavioural outcomes suggest potential for
      intervention effectiveness. Long-term follow-up is needed to reveal residual
      benefits of enhanced parenting skills on environmental lifestyle changes.

PMID- 21740604
TI  - Brief cognitive behavioural therapy for hallucinations: can it help people who
      decide not to take antipsychotic medication? A case report.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) can be helpful for many people
      who experience psychosis; however most research trials have been conducted with
      people also taking antipsychotic medication. There is little evidence to know
      whether CBT can help people who choose not to take this medication, despite this
      being a very frequent event. Developing effective alternatives to antipsychotics
      would offer service users real choice. AIMS: To report a case study illustrating
      how brief CBT may be of value to a young person experiencing psychosis and not
      wishing to take antipsychotic medication. METHOD: We describe the progress of
      brief CBT for a young man reporting auditory and visual hallucinations in the
      form of a controlling and dominating invisible companion. We describe the
      formulation process and discuss the impact of key interventions such as
      normalising and detached mindfulness. RESULTS: Seven sessions of CBT resulted in
      complete disappearance of the invisible companion. The reduction in frequency and
      duration followed reduction in conviction in key appraisals concerning
      uncontrollability and unacceptability. CONCLUSIONS: This case adds to the
      existing evidence base by suggesting that even short-term CBT might lead to
      valued outcomes for service users experiencing psychosis but not wishing to take
      antipsychotic medication.

PMID- 21740605
TI  - Transcatheter closure of a large left ventricular pseudoaneurysm using an
      Amplatzer Vascular Plug 4 and stenting of the inferior caval vein in a child.
AB  - Left ventricular pseudoaneurysm is especially rare in childhood, and its main
      treatment option should be surgery. We describe the case of a 9.5-year-old boy
      who first underwent mitral vegetation excision and then an unsuccessful
      pseudoaneurysm operation. Owing to pseudoaneurysmal sac dimensions, inferior
      caval vein syndrome developed. We delivered the Amplatzer Vascular Plug 4 into
      the pseudoaneurysm and treated the inferior caval vein syndrome with a bare
      Cheatham-Platinum stent. The patient was asymptomatic at the last follow-up.

PMID- 21740606
TI  - Use of a self-expanding custom-made stent graft to treat lateral tunnel leak,
      stenosis, and fenestration in the Fontan pathway.
AB  - A 12-year-old girl with hypoplastic right heart, double inlet left ventricle, and
      transposition of the great arteries had a lateral tunnel Fontan operation 8 years
      previously. She developed symptoms related to a combination of stenosis in the
      inferior caval venous pathway, a fenestration, and leak in the lateral tunnel.
      These were successfully treated with a custom-made stent graft.

PMID- 21740607
TI  - Device closure of atrial septal defect: medium-term outcome with special
      reference to complications.
AB  - BACKGROUND: There are concerns over the outcome of device closure of secundum
      atrial septal defect with special reference to erosions and aortic regurgitation.
      AIM: To assess the medium-term outcome of device closure of atrial septal defects
      with special reference to complications. METHODS: A total of 205 patients with
      secundum atrial septal defects underwent transcatheter closure from October, 1999
      to April, 2009. The median age was 18 (1.4-55) years. Amplatzer Septal Occluder
      was used in all the patients. Medium-term follow-up was available in 176 of 200
      (88%) patients. RESULTS: Device closure was successful in 200 out of 205 (98%)
      patients. The device embolised in four patients and was associated with short
      inferior caval vein margin (p = 0.003). Balloon sizing in 71 patients (35%)
      resulted in implantation of a larger device (p = 0.002). Early complications
      included pericardial effusion, 2:1 heart block, and infective endocarditis (1
      patient each). There were eight patients who reported migraine (3.9%). At median
      follow-up of 5.8 (0.6-10.3) years, complete closure occurred in 197 out of 200
      patients. Short superior caval vein margin was associated with a residual shunt
      (p < 0.001). There were two patients who developed mild aortic regurgitation
      (1%), which correlated with a device-to-defect ratio of >1.3:1 (p = 0.001). There
      were no erosions, late embolisation, or thromboembolism. Atrial fibrillation
      occurred in three adults (1.5%). CONCLUSIONS: Device closure of secundum atrial
      septal defects using Amplatzer Septal Occluder is safe and effective in the
      medium term. Short inferior caval vein margin correlates with increased risk of
      embolisation and short superior caval vein margin with a residual shunt. The risk
      of developing aortic regurgitation is low and correlates with increased device-to
      defect ratio.

PMID- 21740608
TI  - Persistent left superior caval vein with absent right superior caval vein:
      importance of awareness.
AB  - Isolated persistent left superior caval vein is a rare anomaly of the systemic
      venous return. We describe an unsuccessful pacemaker implantation through the
      right subclavian vein, which later turned out to be due to a venous anomaly. This
      case and some other cases show that with the help of a multidetector computed
      tomography, an isolated persistent left superior caval vein is not a
      contraindication for subclavian approached pacemaker insertion.

PMID- 21740609
TI  - Quantification of left-to-right shunt through patent ductus arteriosus by colour
      Doppler in children admitted for a device closure.
AB  - PURPOSE: Our animal model suggests that quantification of ductal flow from colour
      Doppler pixels is possible. We aimed to clarify whether this method can be used
      to determine a clinically significant ductal shunt in children. METHODS: We
      retrospectively quantified ductal flow from saved images from 20 children who had
      been admitted for device occlusion of patent ductus arteriosus. Colour Doppler
      images over the main stem of the pulmonary artery were obtained in longitudinal
      cross-sections. The colour pixel percentages during diastole, representing ductal
      flow, were correlated with the documented shunt, measured invasively according to
      Fick's principle. RESULTS: The ratio of pulmonary to systemic flow correlated
      best with the sum of the percentages of green colour pixels (r = 0.73, r2 = 0.54,
      p < 0.001). When the shunt was 1.5:1 or more, 12 out of 13 infants had 50% or
      more of the region of interest covered with green pixels--sensitivity 92%,
      specificity 71%. The correlation between ductal diameter and pulmonary-to
      systemic flow ratio was less significant (r = 0.6, r2 = 0.37, p < 0.03).
      CONCLUSIONS: We conclude that clinically significant shunts with pulmonary-to
      systemic flow ratio over 1.5 can be diagnosed with this method where neither the
      size of the patient nor echocardiographic settings seem to be critical. The
      method could be used to provide an objective indication for ductal closure, but
      further prospective studies in children are needed to verify the power of the
      method.

PMID- 21740610
TI  - Hepatitis B prevalence in the Turkish population of Arnhem: implications for
      national screening policy?
AB  - Despite the increased prevalence of hepatitis B and C in most migrant groups in
      The Netherlands, a national screening policy for these infections is not
      available. In order to estimate the prevalence of hepatitis B and C in the
      largest group of first-generation migrants (FGM) in The Netherlands, we conducted
      a screening project in the Turkish community of Arnhem. In a separate project we
      identified patients from the target population with chronic hepatitis B and C
      from hospital records (1990-2008). Educational meetings concerning hepatitis were
      organized, with all participants being offered a blood screening test.
      Participants were tested for hepatitis B surface antigen (HBsAg), antibodies to
      hepatitis B core antigen (anti-HBc) and antibodies to hepatitis C virus (anti
      HCV). In total 709 persons were tested, a complete dataset was available for 647
      patients. We found that 3.0% and 0.4% of Turkish FGM aged >24 years in Arnhem had
      active hepatitis B, defined as HBsAg positive, and tested positive for anti-HCV,
      respectively. The hospital records revealed another 32 patients, 28 with
      hepatitis B and four with hepatitis C representing 0.7% for hepatitis B and 0.1%
      for hepatitis C in relation to the total number of Turkish FGM in Arnhem. We
      believe that active hepatitis screening of FGM from Turkey should be part of the
      national health policy as it will benefit the individual and public health.

PMID- 21740611
TI  - Emergency oral rabies vaccination of foxes in Italy in 2009-2010: identification
      of residual rabies foci at higher altitudes in the Alps.
AB  - Following a resurgence of fox rabies in northeastern Italy in 2008-2009, two
      emergency oral rabies vaccination (ORV) campaigns were performed in the Alpine
      mountain ranges in 2009 and 2010 using aerial distribution to prevent the disease
      from spreading further inland. Vaccine baits were distributed only below the
      freezing point altitude, 1000 m above sea level (a.s.l.) in December 2009-January
      2010 and 1500 m a.s.l. in April-May 2010, to avoid repeated freeze-thaw cycles.
      Spatial analysis unexpectedly identified fox rabies hotspots above the threshold
      altitudes, probably representing local residual rabies foci which may have
      contributed to maintaining the infectious cycle in areas not vaccinated at higher
      altitudes. Based on the results obtained, in May 2010, the second ORV campaign
      was extended to include threshold altitudes of up to 2300 m a.s.l. to eliminate
      residual foci. The observations made may help in the formulation of ORV
      strategies in countries sharing similar topographical features.

PMID- 21740612
TI  - Temporo-parietal brain activity as a longitudinal predictor of response to
      educational interventions among middle school struggling readers.
AB  - Spatiotemporal brain activation profiles were obtained from 27 middle school
      students experiencing difficulties in reading comprehension as well as word-level
      skills (RD) and 23 age- and IQ-matched non-reading impaired students during
      performance of an oral pseudoword reading task using Magnetoencephalography
      (MEG). Based on their scores on standardized reading fluency tests 1 year later,
      students with RD who showed significant improvement were classified as Adequate
      Responders (AR) whereas those not demonstrating such gains were classified as
      Inadequate Responders (IR). At baseline, activation profiles of the AR group
      featured increased activity in the left supramarginal and angular gyri, as well
      as in the superior and middle temporal gyri, bilaterally compared to IR. The
      degree of activity in these regions was a significant predictor of the amount of
      subsequent gains in reading fluency. These results extend previous functional
      brain imaging findings of beginning readers, suggesting that recruitment of brain
      areas that typically serve as key components of the brain circuit for reading is
      an important factor in determining response to intervention in older struggling
      readers.

PMID- 21740613
TI  - Frontotemporal atrophy associated with paranoid delusions in women with
      Alzheimer's disease.
AB  - BACKGROUND: Paranoid delusions are a common and difficult-to-manage feature of
      Alzheimer's disease (AD). We investigated the neuroanatomical correlates of
      paranoid delusions in a cohort of AD patients, using magnetic resonance imaging
      (MRI) to measure regional volume and regional cortical thickness. METHODS: 113
      participants with probable AD were assessed for severity of disease, cognitive
      and functional impairment. Presence and type of delusions were assessed using the
      Neuropsychiatric Inventory (NPI). Structural MRI images were acquired on a 1.5 T
      scanner, and were analyzed using an automated analysis pipeline. RESULTS:
      Paranoid delusions were experienced by 23 (20.4%) of the participants. Female
      participants with paranoid delusions showed reduced cortical thickness in left
      medial orbitofrontal and left superior temporal regions, independently of
      cognitive decline. Male participants with delusions did not show any significant
      differences compared to males without delusions. An exploratory whole brain
      analysis of non-hypothesized regions showed reduced cortical thickness in the
      left insula for female participants only. CONCLUSION: Frontotemporal atrophy is
      associated with paranoid delusions in females with AD. Evidence of sex
      differences in the neuroanatomical correlates of delusions as well as differences
      in regional involvement in different types of delusions may be informative in
      guiding management and treatment of delusions in AD.

PMID- 21740614
TI  - The clinical significance of cognition-focused interventions for cognitively
      impaired older adults: a systematic review of randomized controlled trials.
AB  - BACKGROUND: Cognitive stimulation, training or rehabilitation can achieve modest,
      skill-specific gains in cognitively healthy older adults. With regard to the
      limited efficacy of currently available anti-dementia drugs it is crucial to
      investigate whether such treatments also provide clinically meaningful benefits
      to cognitively impaired older individuals. METHODS: We conducted a systematic
      review of randomized controlled trials evaluating cognition-focused interventions
      in participants with mild cognitive impairment or dementia. Meta-analytic
      strategies were used to calculate effect sizes. RESULTS: Cognition-focused
      interventions confer small and inconsistent effects on trained cognitive skills
      which, according to some studies, translate into gains on general cognitive
      ability. Instruments measuring such effects such as the Mini-Mental State
      Examination (MMSE) or the Alzheimer's Disease Assessment Scale, cognitive part
      (ADAS-Cog) show standardized mean differences of 0.20 and 0.30, respectively,
      which are comparable with those of current antidementia drug treatments. However,
      convincing evidence of clinical significance was only obtained from single trials
      in terms of delay of cognitive decline, improvement in activities of daily
      living, or enhanced attainment of personally relevant goals. CONCLUSIONS: The
      potential of cognition-focused interventions has probably been obscured by the
      methodological inconsistencies and limitations of the clinical studies conducted
      thus far. Further randomized controlled trials on the efficacy of these treatment
      modalities are required using optimized and consistent methods. Emphasis should
      be placed on tailoring interventions to individual needs and resources while
      maintaining a high level of standardization, on implementing newly acquired
      skills and strategies in the everyday context, on appropriate treatment duration,
      and on including person-centered outcomes.

PMID- 21740615
TI  - Introduction to stem cell special section.

PMID- 21740616
TI  - The significant role of centrosomes in stem cell division and differentiation.
AB  - The role of centrosomes in stem cell division has recently been highlighted and
      further ascribes important functions to centrosomes in stem cell maintenance,
      cellular differentiation, and development. Advanced cell and molecular studies
      coupled with immunofluorescence, electron microscopy, and live cell imaging of
      specific centrosome proteins have contributed greatly to our knowledge of
      centrosome composition, structure, and dynamics and have uncovered new insights
      into mechanisms of centrosome functions in asymmetric cell division. The
      establishment of asymmetry and differential positioning of mother and daughter
      centrosomes during stem cell mitosis is important for allowing one cell to
      maintain stem cell characteristics while the sibling cell undergoes
      differentiation. Another key role for centrosomes has been revealed in primary
      cilia of embryonic stem cells that play significant roles in cellular signaling
      and are therefore critically important for stem cell decisions. Studies of
      signaling through primary cilia may contribute important information that may aid
      in the production of specific cells that are suitable for tissue repair and
      regeneration in the field of regenerative medicine.

PMID- 21740617
TI  - Age-dependent expression of collagen receptors and deformation of type I collagen
      substrates by rat cardiac fibroblasts.
AB  - Little is known about how age influences the ways in which cardiac fibroblasts
      interact with the extracellular matrix. We investigated the deformation of
      collagen substrates by neonatal and adult rat cardiac fibroblasts in monolayer
      and three-dimensional (3D) cultures, and quantified the expression of three
      collagen receptors [discoidin domain receptor (DDR)1, DDR2, and beta1 integrin]
      and the contractile protein alpha smooth muscle actin (alpha-SMA) in these cells.
      We report that adult fibroblasts contracted 3D collagen substrates significantly
      less than their neonate counterparts, whereas no differences were observed in
      monolayer cultures. Adult cells had lower expression of beta1 integrin and alpha
      SMA than neonate cultures, and we detected significant correlations between the
      expression of alpha-SMA and each of the collagen receptors in neonate cells but
      not in adult cells. Consistent with recent work demonstrating age-dependent
      interactions with myocytes, our results indicate that interactions between
      cardiac fibroblasts and the extracellular matrix change with age.

PMID- 21740618
TI  - Quantitative electron microscopy of cellulose nanofibril structures from
      Eucalyptus and Pinus radiata kraft pulp fibers.
AB  - This work comprises the structural characterization of Eucalyptus and Pinus
      radiata pulp fibers and their corresponding fibrillated materials, based on
      quantitative electron microscopy techniques. Compared to hardwood fibers, the
      softwood fibers have a relatively open structure of the fiber wall outer layers.
      The fibrillation of the fibers was performed mechanically and chemi-mechanically.
      In the chemi-mechanical process, the pulp fibers were subjected to a TEMPO
      mediated oxidation to facilitate the homogenization. Films were made of the
      fibrillated materials to evaluate some structural properties. The thicknesses and
      roughnesses of the films were evaluated with standardized methods and with
      scanning electron microscopy (SEM), in backscattered electron imaging mode. Field
      emission SEM (FE-SEM) and transmission electron microscopy (TEM) were performed
      to quantify the nanofibril morphology. In this study, we give additional and
      significant evidences about the suitability of electron microscopy techniques for
      quantification of nanofibril structures. In addition, we conclude that standard
      methods are not suitable for estimating the thickness of films having relatively
      rough surfaces. The results revealed significant differences with respect to the
      morphology of the fibrillated material. The differences are due to the starting
      raw material and to the procedure applied for the fibrillation.

PMID- 21740619
TI  - The assessment of food security in homeless individuals: a comparison of the Food
      Security Survey Module and the Household Food Insecurity Access Scale.
AB  - OBJECTIVE: To compare the Household Food Insecurity Access Scale (HFIAS), the US
      Food Security Survey Module (US FSSM) and a modified version of the US FSSM in
      which references to buying food were changed to references to getting food, in
      terms of their classification of food security levels among homeless individuals,
      and to determine which of these instruments was most preferred by homeless
      individuals. DESIGN: A cross-sectional survey. SETTING: Recruitment of
      participants took place at seven shelters and from three drop-in programmes that
      serve homeless individuals in Toronto, Canada. SUBJECTS: Fifty individuals who
      were >=18 years of age, able to communicate in English and currently homeless.
      RESULTS: The modified US FSSM assigned 20% of participants to a lower ordinal
      food security category compared with the US FSSM, and only 8% to a higher food
      security category. The HFIAS assigned 30% of participants to a lower food
      security category compared with either the US FSSM or the modified US FSSM, and
      only 10-16% of participants to a higher food security category. When asked to
      compare all three instruments, the majority of respondents (62%) selected the
      HFIAS as the best instrument for people who are homeless. CONCLUSIONS: A majority
      of homeless individuals selected the HFIAS as the best food security instrument
      for people who are homeless. Our findings suggest that the HFIAS is a more
      appropriate instrument than the US FSSM for measuring food security in the
      homeless population.

PMID- 21740620
TI  - Socio-economic differences in takeaway food consumption among adults.
AB  - OBJECTIVE: To examine socio-economic differences in the frequency and types of
      takeaway foods consumed. DESIGN: A cross-sectional postal survey. SETTING:
      Participants were asked about their usual consumption of overall takeaway food
      (<4 times/month or >=4 times/month) and of twenty-two specific takeaway food
      items (<1 time/month or >=1 time/month); these latter foods were grouped into
      'healthy' and 'less healthy' choices. Socio-economic position was measured on the
      basis of educational level and equivalised household income, and differences in
      takeaway food consumption were assessed by calculating prevalence ratios using
      log binomial regression. SUBJECTS: Adults aged 25-64 years from Brisbane,
      Australia, were randomly selected from the electoral roll (n 903; 63.7 % response
      rate). RESULTS: Compared with their more educated counterparts, the least
      educated were more regular consumers of overall takeaway food and fruit or
      vegetable juice and less regular consumers of sushi. For the 'less healthy'
      items, the least educated more regularly consumed potato chips, savoury pies,
      fried chicken and non-diet soft drinks; however, the least educated were less
      likely to consume curry. Household income was not associated with overall
      takeaway consumption. The lowest-income group was a more regular consumer of
      fruit or vegetable juice compared with the highest-income group. Among the 'less
      healthy' items, the lowest-income group was a more regular consumer of fried
      fish, ice cream and milk shakes, whereas curry was consumed less regularly.
      CONCLUSIONS: The frequency and types of takeaway foods consumed by socio
      economically disadvantaged groups may contribute to inequalities in overweight or
      obesity and to chronic disease.

PMID- 21740621
TI  - High rates of serum selenium deficiency among HIV- and HCV-infected and
      uninfected drug users in Buenos Aires, Argentina.
AB  - OBJECTIVE: To describe the prevalence of low serum Se and determine whether HIV,
      hepatitis C virus (HCV) and/or the types of drugs used are associated with serum
      Se in a cohort of infected and uninfected drug users. DESIGN: Independent
      correlates of low serum Se levels based on data collected from food recalls,
      physical examinations and clinical questionnaires were identified using
      multivariate regression analysis. SETTING: Buenos Aires, Argentina SUBJECTS: A
      total of 205 (twenty-five female and 180 male) former and current drug users.
      RESULTS: Drug users had an average serum Se level of 69.8 (sd 32.8) MUg/d,
      [corrected] and 82 % were considered deficient (<85 MUg/l). [corrected]
      Multivariate analyses found that HIV- and/or HCV-infected individuals had lower
      mean Se compared with healthy, uninfected drug users (HIV/HCV co-infection: -25.3
      MUg/l (se 7.6), P = 0.001; HIV alone: -28.9 MUg/l (se 6.9), P < 0.001; HCV alone:
      -19.4 MUg/l (se 7.1), P = 0.006). Current and previous drug use was associated
      with higher serum Se. Cigarette smoking and heavy alcohol consumption were not
      found to be associated with Se status. CONCLUSIONS: Low serum Se levels are
      highly prevalent among drug users in Buenos Aires, Argentina. Se supplementation
      and/or dietary interventions may be warranted in drug users who are at high risk
      for HIV and/or HCV infection.

PMID- 21740622
TI  - Automatic sensory information processing abnormalities across the illness course
      of schizophrenia.
AB  - BACKGROUND: Deficits in automatic sensory discrimination, as indexed by a
      reduction in the mismatch negativity (MMN) and P3a event-related potential
      amplitudes, are well documented in chronic schizophrenia. However, MMN and P3a
      have not been sufficiently studied early in the course of psychotic illness. The
      present study aimed to investigate MMN, P3a and reorienting negativity (RON)
      across the course of schizophrenia. METHOD: MMN, P3a, and RON were assessed in
      118 subjects across four groups: (1) individuals at risk for psychosis (n=26);
      (2) recent-onset patients (n=31); (3) chronic patients (n=33); and (4) normal
      controls (n=28) using a duration-deviant auditory oddball paradigm. RESULTS:
      Frontocentral deficits in MMN and P3a were present in all patient groups. The at
      risk group's MMN and P3a amplitudes were intermediate to those of the control and
      recent-onset groups. The recent-onset and chronic patients, but not the at-risk
      subjects, showed significant RON amplitude reductions, relative to the control
      group. Associations between MMN, P3a, RON and psychosocial functioning were
      present in the chronic patients. In the at-risk subjects, P3a and RON deficits
      were significantly associated with higher levels of negative symptoms.
      CONCLUSIONS: Abnormalities in the automatic processes of sensory discrimination,
      orienting and reorienting of attention are evident in the early phases of
      schizophrenia and raise the possibility of progressive worsening across stages of
      the illness. The finding that MMN and P3a, but not RON, were reduced before
      psychosis onset supports the continued examination of these components as
      potential early biomarkers of schizophrenia.

PMID- 21740623
TI  - Movement abnormalities and psychotic-like experiences in childhood: markers of
      developing schizophrenia?
AB  - BACKGROUND: Both involuntary dyskinetic movements and psychotic-like experiences
      (PLEs) are reported to be antecedents of schizophrenia that may reflect
      dysfunctional dopaminergic activity in the striatum. The present study compared
      dyskinetic movement abnormalities displayed by children with multiple antecedents
      of schizophrenia (ASz), including speech and/or motor developmental lags or
      problems, internalising/externalising problems in the clinical range, and PLEs,
      with those displayed by children with no antecedents (noASz). METHOD: The sample
      included 21 ASz and 31 noASz children, aged 9-12 years old. None had taken
      psychotropic medication or had relatives with psychosis. The antecedents of
      schizophrenia were assessed using questionnaires completed by children and
      caregivers. A trained rater, blind to group status, coded dyskinetic movement
      abnormalities using a validated tool from videotapes of interviews with the
      children. RESULTS: ASz children reported, on average, 'certain experience' of 2.5
      PLEs, while noASz children, by definition, reported none. The ASz children, as
      compared with noASz children, displayed significantly more dyskinetic movement
      abnormalities in total, and in the facial and the upper-body regions, after
      controlling for sex and age. Receiver operator characteristics analyses yielded
      high area under the curve values for the total score (0.94), facial score (0.91)
      and upper-body score (0.86), indicating that these scores distinguished between
      the ASz and noASz children with great accuracy. CONCLUSIONS: Brief questionnaires
      identified children with multiple antecedents of schizophrenia who displayed
      significantly more involuntary dyskinetic movement abnormalities than children
      without antecedents. The presence of PLEs and dyskinesias could reflect early
      disruption of striatal dopamine circuits.

PMID- 21740624
TI  - Acceptance and commitment therapy as guided self-help for psychological distress
      and positive mental health: a randomized controlled trial.
AB  - BACKGROUND: In order to reduce the high prevalence of depression, early
      interventions for people at risk of depression are warranted. This study
      evaluated the effectiveness of an early guided self-help programme based on
      acceptance and commitment therapy (ACT) for reducing depressive symptomatology.
      METHOD: Participants with mild to moderate depressive symptomatology were
      recruited from the general population and randomized to the self-help programme
      with extensive email support (n=125), the self-help programme with minimal email
      support (n=125) or to a waiting list control group (n=126). Participants
      completed measures before and after the intervention to assess depression,
      anxiety, fatigue, experiential avoidance, positive mental health and mindfulness.
      Participants in the experimental conditions also completed these measures at a 3
      month follow-up. RESULTS: In the experimental conditions significant reductions
      in depression, anxiety, fatigue, experiential avoidance and improvements in
      positive mental health and mindfulness were found, compared with the waiting list
      condition (effect sizes Cohen's d=0.51-1.00). These effects were sustained at the
      3-month follow-up. There were no significant differences between the experimental
      conditions on the outcome measures. CONCLUSIONS: The ACT-based self-help
      programme with minimal email support is effective for people with mild to
      moderate depressive symptomatology.

PMID- 21740625
TI  - Affective functioning and social cognition in Noonan syndrome.
AB  - BACKGROUND: Noonan syndrome (NS) is a common genetic disorder, characterized by
      short stature, facial dysmorphia, congenital heart defects and a mildly lowered
      IQ. Impairments in psychosocial functioning have often been suggested, without,
      however, systematic investigation in a clinical group. In this study, different
      aspects of affective processing, social cognition and behaviour, in addition to
      personal well-being, were assessed in a large group of patients with NS. METHOD:
      Forty adult patients with NS were compared with 40 healthy controls, matched with
      respect to age, sex, intelligence and education level. Facial emotion recognition
      was measured with the Emotion Recognition Task (ERT), alexithymia with both the
      20-item Toronto Alexithymia Scale (TAS-20) and the Bermond-Vorst Alexithymia
      Questionnaire (BVAQ), and mentalizing with the Theory of Mind (ToM) test. The
      Symptom Checklist-90 Revised (SCL-90-R) and the Scale for Interpersonal Behaviour
      (SIB) were used to record aspects of psychological well-being and social
      interaction. RESULTS: Patients showed higher levels of cognitive alexithymia than
      controls. They also experienced more social distress, but the frequency of
      engaging in social situations did not differ. Facial emotion recognition was only
      slightly impaired. CONCLUSIONS: Higher levels of alexithymia and social
      discomfort are part of the behavioural phenotype of NS. However, patients with NS
      have relatively intact perception of emotions in others and unimpaired
      mentalizing. These results provide insight into the underlying mechanisms of
      social daily life functioning in this patient group.

PMID- 21740626
TI  - Amygdala to hippocampal volume ratio is associated with negative memory bias in
      healthy subjects.
AB  - BACKGROUND: Negative memory bias is thought to be one of the main cognitive risk
      and maintenance factors for depression, but its neural substrates are largely
      unknown. Here, we studied whether memory bias is related to amygdala and
      hippocampal volume, two structures that are critical for emotional memory
      processes and that show consistent volume alterations in depression. METHOD:
      Structural magnetic resonance imaging (MRI) was carried out in 272 healthy
      participants (62% female, 18-50 years old). All images were acquired on 1.5 T
      Siemens MRI scanners. Automatic segmentation of amygdala and hippocampus was
      performed using the FIRST module of FSL. Negative memory bias was assessed by the
      self-referent encoding/evaluation test. RESULTS: Negative memory bias was
      associated with larger amygdala (p=0.042) and smaller hippocampal (p=0.029)
      volumes. In additional analyses, we found that, compared with the associations
      found with hippocampus and amygdala volume separately, a stronger association was
      found between negative memory bias and the ratio of amygdala:hippocampus volume
      (p=0.021). CONCLUSIONS: In non-depressed subjects we found that larger amygdala
      and smaller hippocampal volumes are associated with negative memory bias. This
      suggests that an increased amygdala:hippocampus volume ratio plays a role in
      cognitive vulnerability often seen in individuals with high risk for depression
      and that these structural brain differences may pre-date the onset of depression.

PMID- 21740627
TI  - Predictors of 1-year outcomes of major depressive disorder among individuals with
      a lifetime diagnosis: a population-based study.
AB  - BACKGROUND: Examining predictors of the outcomes of major depressive disorder
      (MDD) is important for clinical practice and population health. There are few
      population-based longitudinal studies on this topic. The objectives of this study
      were to (1) estimate the proportions of persistent and recurrent MDD among those
      with MDD over 1 year, and (2) identify demographic, socio-economic, workplace
      psychosocial and clinical factors associated with the outcomes. METHOD: From a
      population-based longitudinal study of the working population, participants with
      a lifetime diagnosis of MDD were selected (n=834). They were classified into two
      groups: those with and those without current MDD. The proportions of 1-year
      persistence and recurrence of MDD were estimated. MDD was assessed by the World
      Health Organization (WHO) Composite International Diagnostic Interview, CIDI-Auto
      2.1, by telephone. RESULTS: The proportions of persistent and recurrent MDD in 1
      year were 38.5% [95% confidence interval (CI) 31.1-46.5] and 13.3% (95% CI 10.2
      17.1) respectively. Long working hours, negative thinking and having co-morbid
      social phobia were predictive of persistence of MDD. Perceived work-family
      conflict, the severity of a major depressive episode and symptoms of depressed
      mood were significantly associated with the recurrence of MDD. CONCLUSIONS:
      Clinical and psychosocial factors are important in the prognosis of MDD. The
      factors associated with persistence and recurrence of MDD may be different. More
      large longitudinal studies on this topic are needed so that clinicians may
      predict potential outcomes based on the clinical profile and provide
      interventions accordingly. They may also take clinical action to change relevant
      psychosocial factors to minimize the chance of persistence and/or recurrence of
      MDD.

PMID- 21740628
TI  - Concurrent and construct validity of Mediterranean diet scores as assessed by an
      FFQ.
AB  - OBJECTIVE: The aim of the present study was to assess the concurrent and
      construct validity of two diet-quality indices, a modified Mediterranean diet
      score (mMDS) and a Mediterranean-like diet score (MLDS) additionally
      incorporating unhealthy food choices, as determined by an FFQ. DESIGN: A
      validation study assessing FFQ intake estimates compared with ten or more
      unannounced 24 h recalls. Pearson's correlation coefficients, intraclass
      correlation coefficients (ICC), Bland-Altman plots and the limits of agreement
      method were used to assess the between-method agreement of scores. Construct
      validity was shown using associations between nutrient intakes derived from
      multiple 24 h recalls and the mMDS and MLDS derived from the FFQ. SETTING:
      Gerona, Spain. SUBJECTS: A total of 107 consecutively selected participants from
      a population-based cross-sectional survey. RESULTS: Pearson's correlations for
      the energy-adjusted mMDS and MLDS compared with multiple recalls were 0.48 and
      0.62, respectively. The average FFQ energy-adjusted mMDS and MLDS were 102 % and
      98 % of the recall-based mMDS and MLDS estimates, respectively. The FFQ under-
      and overestimated dietary recall estimates of the energy-adjusted MLDS by 28 %
      and 25 %, respectively, with slightly wider boundaries for the mMDS (31 % and 34
      %). The ICC, which assesses absolute agreement, was similar to Pearson's
      correlations (mMDS = 0.48 and MLDS = 0.61). The mean differences between methods
      were similar across the range of average ratings for both scores, indicating the
      absence of bias. The FFQ-derived mMDS and MLDS correlated in the anticipated
      directions with intakes of eleven (73.3 %) and thirteen of fifteen nutrients
      (86.7 %), respectively. CONCLUSIONS: The FFQ provides valid estimates of diet
      quality as assessed by the mMDS and MLDS.

PMID- 21740629
TI  - Transforming growth factor-beta1 polymorphisms and chronic obstructive pulmonary
      disease: a meta-analysis.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex polygenic
      disease in which gene- environment interactions play a critical role in disease
      onset and progression. Transforming growth factor-beta 1 (TGF-beta 1) is one of
      several candidate loci for the pathogenesis of COPD, and is highly polymorphic.
      OBJECTIVE: To derive a more precise estimation of the relationship between the
      T869C and C-509T polymorphisms of the TGF-beta 1 gene and COPD, a meta-analysis
      of 11 published case-control studies was performed. METHODS: Ten studies with
      1507 cases and 2542 controls for T869C polymorphism and six studies with 955
      cases and 2136 controls for C-509T polymorphism were included. The pooled odds
      ratios were performed respectively for allele contrasts, additive genetic model,
      dominant genetic model and recessive genetic model. A subgroup analysis was also
      performed by ethnicity for T869C polymorphism. RESULTS: With respect to T869C
      polymorphism, a significant association of TGF-beta 1 gene polymorphism at 869T/C
      with COPD was observed in the overall analysis (C vs. T: OR 0.82, 95%CI 0.70
      0.96, P = 0.01). In the subgroup analysis by ethnicity, significant risks were
      also found in the Caucasian population for C vs. T (OR 0.77, 95%CI 0.60-0.98, P =
      0.03), but not in the Asian population (C vs. T: OR 0.88, 95%CI 0.76-1.03, P =
      0.10). With respect to C-509T polymorphism, no significant association with COPD
      was demonstrated in the overall analysis (T vs. C: OR 0.84, 95%CI 0.68- 1.04, P =
      0.11). CONCLUSION: Potentially functional TGF-beta 1 T869C polymorphism may play
      a low penetrance role in COPD susceptibility in an ethnicity-specific manner.

PMID- 21740631
TI  - Determination of absolute configuration of chiral molecules using vibrational
      optical activity: a review.
AB  - Determination of the absolute handedness, known as absolute configuration (AC),
      of chiral molecules is an important step in any field related to chirality,
      especially in the pharmaceutical industry. Vibrational optical activity (VOA) has
      become a powerful tool for the determination of the AC of chiral molecules in the
      solution state after nearly forty years of evolution. VOA offers a novel
      alternative, or supplement, to X-ray crystallography, permitting AC
      determinations on neat liquid, oil, and solution samples without the need to grow
      single crystals of the pure chiral sample molecules as required for X-ray
      analysis. By comparing the sign and intensity of the measured VOA spectrum with
      the corresponding ab initio density functional theory (DFT) calculated VOA
      spectrum of a chosen configuration, one can unambiguously assign the AC of a
      chiral molecule. Comparing measured VOA spectra with calculated VOA spectra of
      all the conformers can also provide solution-state conformational populations.
      VOA consists of infrared vibrational circular dichroism (VCD) and vibrational
      Raman optical activity (ROA). Currently, VCD is used routinely by researchers in
      a variety of backgrounds, including molecular chirality, asymmetric synthesis,
      chiral catalysis, drug screening, pharmacology, and natural products. Although
      the application of ROA in AC determination lags behind that of VCD, with the
      recent implementation of ROA subroutines in commercial quantum chemistry
      software, ROA will in the future complement VCD for AC determination. In this
      review, the basic principles of the application of VCD to the determination of
      absolute configuration in chiral molecules are described. The steps required for
      VCD spectral measurement and calculation are outlined, followed by brief
      descriptions of recently published papers reporting the determination of AC in
      small organic, pharmaceutical, and natural product molecules.

PMID- 21740632
TI  - Dependence of signal on depth in transmission Raman spectroscopy.
AB  - Recently, transmission Raman spectroscopy has been shown to be a valuable tool in
      the volumetric quantification of pharmaceutical formulations. In this work a
      Monte Carlo simulation and experimental study are performed to elucidate the
      dependence of the Raman signal on depth from the viewpoint of probing
      pharmaceutical tablets and powders in this experimental configuration. The
      transmission Raman signal is shown to exhibit a moderate bias toward the center
      of the tablets and this can be considerably reduced by using a recently developed
      Raman signal-enhancing concept, the "photon diode." The enhancing element not
      only reduces the bias but also increases the overall Raman signal intensity and
      consequently improves the signal-to-noise ratio of the measured spectrum.
      Overall, its implementation with appropriately chosen reflectivity results in a
      more uniform volumetric sampling across the half of the tablet where the photon
      diode is used (or across the tablet's entire depth if two photon diodes are used
      on each side of tablet) and enhanced overall sensitivity. These findings are
      substantiated experimentally on a segmented tablet by inserting a poly(ethelyne
      terephthalate) (PET) film doped with TiO(2) at different depths and monitoring
      its contribution to the overall transmission Raman signal from the segmented
      tablet. The numerical simulations also indicate considerable sensitivity of the
      overall Raman signal to the absorption of the sample, which is in line with large
      migration distances traversed by photons in these measurements. The presence of
      sample absorption was shown numerically to reduce the signal enhancement effect
      while the overall depth-dependence profile remained broadly unchanged. The
      absorption was also shown to produce a depth profile with the photon diode
      similar to that without it, although with a reduced absolute intensity of Raman
      signals and diminished enhancement effect.

PMID- 21740633
TI  - Dynamic rastering surface-enhanced Raman scattering (SERS) measurements on silver
      nanorod substrates.
AB  - Surface-enhanced Raman spectra of a thiol-modified biotin derivative on oblique
      angle-deposited silver nanorod (AgNR) array substrates were measured using both
      static and rotating rastering methods. We find that the rotating rastering method
      has a strong tendency to decrease the point-to-point relative standard deviation
      (RSD) compared to static measurements as well as decrease the effects of
      cumulative excitation exposure. The AgNR substrates treated with the modified
      biotin typically demonstrate intra-substrate RSDs of <10%, with an average RSD of
      ~3% when the rastering radius r=1 mm. The quantitative studies on the
      relationship between rastering radius, sampling area, and rastering frequency
      show that only the rastering radius appears to have significant effect on the
      measured RSD. Our results demonstrate that under the proper measurement and
      sample preparation conditions, the Ag nanorod substrates are very uniform.

PMID- 21740634
TI  - Surface-enhanced vibrational spectroscopy of adsorbates on microemulsion
      synthesized gold nanoparticles.
AB  - Very small (<10 nm) monodisperse gold nanoparticles (AuNPs) coated with a
      monolayer of decanethiol were prepared and their surface-enhanced infrared
      absorption (SEIRA) spectra were measured in the transmission mode. The AuNPs were
      prepared by the borohydride reduction of HAuCl(4) inside reverse micelles that
      were made by adding water to a hexane solution of sodium bis(2
      ethylhexyl)sulfosuccinate (AOT). The gold nanoparticles were then stabilized by
      the addition of decanethiol. Subsequent addition of p-nitrothiophenol both
      facilitated the removal of excess AOT and showed that the gold surface was
      completely covered by the decanethiol. SEIRA spectra of decanethiol on gold
      particles prepared in AOT microemulsions were about twelve times more intense
      than corresponding layers on gold produced by electroless deposition and gave a
      significantly less noisy spectrum compared to the corresponding surface-enhanced
      Raman spectrum. The surface-enhanced Raman scattering (SERS) spectra of the same
      samples showed that the most intense spectrum was obtained from gold
      nanoparticles with a mean diameter of 2.5 nm. This result is in contrast to
      previous statements that SERS spectra could only be obtained from particles
      larger than 10 nm.

PMID- 21740635
TI  - Finite frequency f-sum rule for assessment of number density of gold
      nanoparticles (AuNPs) and Kramers-Kronig relation for refractive index of
      colloidal gold.
AB  - Absorption spectra from colloids containing different concentrations of spherical
      gold nanoparticles in water were measured with a spectrophotometer. The
      absorption spectra were used to calculate the number density of nanoparticles
      (NPs) with the aid of an unconventional finite spectral band f-sum rule applied
      for gold colloid. Good correlation between the number density of dispersion
      electrons, obtained from the f-sum rule, and the number density of nanoparticles
      was found. The effective absolute refractive index of the gold colloid was
      obtained with the aid of a singly subtractive Kramers-Kronig relation, and in
      addition the refractive index change due to the nanoparticles was obtained with
      the aid of a conventional Kramers-Kronig relation. Such optical properties are
      valuable in studies of light interaction with nanoparticles.

PMID- 21740636
TI  - Surface-enhanced infrared absorption (SEIRA) of adsorbates on copper
      nanoparticles synthesized by galvanic displacement.
AB  - Copper nanoparticles (Cu NPs) were made by electroless deposition on Ge disks as
      substrates for surface-enhanced infrared absorption (SEIRA). Previous X-ray
      photoelectron spectra had shown that elemental copper is deposited on the Ge
      substrate and that the nanoparticulate film remains resistant to oxidation even
      after several days of air exposure at room temperature. SEIRA spectra of p
      nitrothiophenol (p-NTP) adsorbed on the copper nanoparticles were measured.
      Freshly made substrates made by electroless deposition gave higher enhancements
      than both the 12-day-old oxidized substrates and substrates made by physical
      vapor deposition. The intensity of the antisymmetric NO(2) stretching band of p
      NTP relative to that of the symmetric stretch was significantly higher for p-NTP
      adsorbed on copper than on silver nanofilms, indicating that the C(2) axis of the
      aromatic ring is tilted with respect to the copper surface.

PMID- 21740637
TI  - Evidence of a structural defect in Ice VII and the side-chain-dependent response
      of small model peptides to increased pressure.
AB  - The effect of high pressure on the OH stretch of dilute HOD in D(2)O was examined
      using high-pressure Fourier transform infrared (FT-IR) spectroscopy. It was found
      that at pressures directly above the ice VI to ice VII transition, ice VII
      displays a splitting in the OH absorption indicative of differing hydrogen
      bonding environments. This result is contrary to published structures of ice VII
      in which each OH oscillator should experience an identical electronic
      environment. The anomalous band was found to decrease in absorbance and finally
      disappear at ~43.0 kbar. In addition, the pressure response of the amide I' and
      II' bands of three small model peptides was examined. Analysis of these bands'
      response to increased pressure indicates significant side-chain dependence of
      their structural rearrangement, which may play a role in the composition of full
      length proteins of barophilic organisms.

PMID- 21740638
TI  - Attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy
      of oxidized polymer-modified bitumens.
AB  - Oxidative age hardening of bitumen results in increasing fatigue susceptibility
      of bituminous mixtures, thus reducing the service life of asphalt pavements.
      Polymer additives to bitumen have been shown to improve its viscoelastic
      properties and, in some cases, reduce the level of bitumen hardening. Fourier
      transform infrared (FT-IR) spectroscopy enables evaluation of oxidation levels in
      bitumen by measuring the concentration of oxygen-containing chemical
      functionalities. This paper summarizes the results of the investigation of
      oxidative age hardening of polymer-modified bitumens (PMB) caused by accelerated
      aging in laboratory conditions. The PMB samples are prepared with different
      concentrations of styrene-butadiene-based co-polymers. Next, the PMB samples are
      aged using standard procedures that employ air blowing at 163  degrees C for 85
      min followed by conditioning the samples at 100  degrees C and 2.1 MPa pressure
      for 20 to 48 hours. The resultant changes in their chemical composition are
      evaluated by portable attenuated total reflection (ATR) spectrometer.
      Measurements of ketone, sulfoxide, and hydroxyl content in PMB samples indicated
      similar oxidation pathways to those of non-modified bitumens. In addition, no
      evidence of polymer degradation due to accelerated aging of PMB was found in this
      study.

PMID- 21740639
TI  - Pixel selection for near-infrared chemical imaging (NIR-CI) discrimination
      between fish and terrestrial animal species in animal protein by-product meals.
AB  - This paper proposes a method based on near-infrared hyperspectral imaging for
      discriminating between terrestrial and fish species in animal protein by-products
      used in livestock feed. Four algorithms (Mahalanobis distance, Kennard-Stone,
      spatial interpolation, and binning) were compared in order to select an
      appropriate subset of pixels for further partial least squares discriminant
      analysis (PLS-DA). The method was applied to a set of 50 terrestrial and 40 fish
      meals analyzed in the 1000-1700 nm range. Models were then tested using an
      external validation set comprising 45 samples (25 fish and 20 terrestrial). The
      PLS-DA models obtained using the four subset-selection algorithms yielded a
      classification accuracy of 99.80%, 99.79%, 99.85%, and 99.61%, respectively. The
      results represent a first step for the analysis of mixtures of species and
      suggest that NIR-CI, providing valuable information on the origin of animal
      components in processed animal proteins, is a promising method that could be used
      as part of the EU feed control program aimed at eradicating and preventing bovine
      spongiform encephalopathy (BSE) and related diseases.

PMID- 21740640
TI  - Blue pigment colors from wall painting churches in danger (Portugal 15th to 18th
      century): identification, diagnosis, and color evaluation.
AB  - Samples of blue wall paint layers from selected 15th to 18th century religious
      mural paintings from southern Portugal (Alentejo) have been analyzed using a
      multi-analytical methodology involving the combination of in situ visible spectro
      colorimetry with microanalytical techniques such as optical and scanning electron
      microscopy and Raman spectroscopy. In situ analyses and micro-sampling were
      carried out in nine different churches, many in an advanced state of
      deterioration. The objectives of this study were: (a) to identify and compare the
      pigments that were used in the blue paint layers across the Alentejo region and
      through time by analysis of the elemental and mineralogical composition and
      pictorial techniques, and (b) to correlate the data between the actual color of
      the paint layer and the state of conservation of the pigments. For the paintings
      dated from the 16th century forward, the results show a generalized use of smalt
      blue. To a lesser extent, natural azurite was used despite the geological
      richness of the region in copper and pyrite ores. In only one painting was an
      optical blue made of carbon black and lime found. The pigments, pure or mixed
      with red and yellow ochres, were coarsely ground and used in different
      concentrations to create three-dimensional effects. These parameters as well as
      the presence of iron oxides in underlayer paints influence the colorimetric
      coordinates in the more transparent smalt blue paint layers. The state of
      conservation of the pigments plays an important role in the alteration of the
      paint color. A clear example of this is the fading of the smalt blue in several
      paintings due to lixiviation processes.

PMID- 21740641
TI  - Development of an apparatus for on-line analysis of unburned carbon in fly ash
      using laser-induced breakdown spectroscopy (LIBS).
AB  - The level of unburned carbon in fly ash is an important criteria for evaluating
      the combustion efficiencies of boilers, as well as the commercial value of the
      produced fly ash. In this work, an automated prototype laser-induced breakdown
      spectroscopy (LIBS) apparatus comprising an isokinetic sampler, a sample
      preparation module, and a LIBS module has been developed for possible application
      to power plants for on-line analysis of unburned carbon in fly ash without being
      affected by the type of coal burned. Emphasis is placed on the structure and
      operation of the LIBS apparatus, the optimum suction capacity selection, the
      analytical methods for estimation of the exact C line intensity, and the proper
      calibration model established for minimizing the matrix effects, which enable the
      minimization of matrix effects and obtaining more accurate compositional
      measurements. Good agreement has been found between the laboratory measurement
      results from the LIBS method and those from the traditional method. The
      measurement accuracy presented here for unburned carbon analysis is estimated to
      be 0.26%, while the average relative error is 3.81%.

PMID- 21740642
TI  - Deep ablation and depth profiling by laser-induced breakdown spectroscopy (LIBS)
      employing multi-pulse laser excitation: application to galvanized steel.
AB  - The potential of a multi-pulse (MP) laser excitation scheme for deep stratigraphy
      of electrolytically galvanized steel using laser-induced breakdown spectrometry
      (LIBS) has been evaluated. For this purpose, a commercial electro-optically (EO)
      Q-switched Nd:YAG laser was employed, where by reducing the delay between the Q
      switch opening and the flash lamp, a train of pulses (up to 11) separated by
      approximately 7.40 MUs was generated during one lamp flashing. Plasma emission
      after each individual laser pulse of the MP sequence was detected by a
      spectrograph equipped with an intensified charge-coupled device (iCCD) detector.
      With MP excitation, the ablation efficiency was increased ten-fold on iron sample
      and 22.5-fold on zinc material with respect to dual-pulse or single-pulse
      excitation. The LIBS signal generated by MP excitation shows an analogous
      enhancement. Although the total energy per shot delivered to samples was only 60
      mJ, it was possible using LIBS to measure the sample stratigraphy up to depths of
      90 MUm on zinc-coated steel sheets. A satisfactory agreement between the Zn
      thickness determined by the MP-LIBS system and data from the manufacturer has
      also been obtained.

PMID- 21740643
TI  - Determination of photoionization cross-sections of different organic molecules
      using gas chromatography coupled to single-photon ionization (SPI) time-of-flight
      mass spectrometry (TOF-MS) with an electron-beam-pumped rare gas excimer light
      source (EBEL): influence of molecular structure and analytical implications.
AB  - This work describes a fast and reliable method for determination of
      photoionization cross-sections (PICS) by means of gas chromatography (GC) coupled
      to single-photon ionization mass spectrometry (SPI-MS). Photoionization
      efficiency (PIE) data for 69 substances was obtained at a photon energy of 9.8 +/
      0.4 eV using an innovative electron-beam-pumped rare gas excimer light source
      (EBEL) filled with argon. The investigated analytes comprise 12 alkylbenzenes as
      well as 11 other substituted benzenes, 23 n-alkanes, ten polyaromatic
      hydrocarbons, seven aromatic heterocycles, and six polyaromatic heterocycles.
      Absolute PICS for each substance at 9.8 eV are calculated from the relative
      photoionization efficiencies of the compounds with respect to benzene, whose
      photoionization cross-section data is well known. Furthermore, a direct
      correlation between the type of benzene substituents and their absolute PICS is
      presented and discussed in depth. Finally, comparison of previously measured
      photoionization cross-sections for 20 substances shows good agreement with the
      data of the present work.

PMID- 21740644
TI  - Ab initio calculations of proline vibrations with and without water: consequences
      on the infrared spectra of proline-rich proteins.
AB  - The infrared spectra of proline-rich proteins display a strong band in the 1450
      cm(-1) region. In the literature, this band has been assigned either to the
      deformation modes of the CH(2) and CH(3) groups or to the CN stretching mode of
      proline residues. In order to establish the correct assignment of this band, the
      impact of proline vibrations in a polypeptide chain is studied and ab initio
      calculations are performed for a model molecule (I) containing a repeat unit of
      polyproline. A strong band is effectively calculated in the 1450 cm(-1) region
      and mostly assigned to CN stretching, whereas, due to the absence of the N-H
      bond, there is no amide II band. These results are in good agreement with the
      spectral features observed in the Fourier transform infrared (FT-IR) spectra of
      gliadins. Moreover, the spectral shifts calculated when a water molecule is
      complexed with (I) are consistent with the hydration effect observed in the
      experimental data.

PMID- 21740645
TI  - Using multiple calibration sets to improve the quantitative accuracy of partial
      least squares (PLS) regression on open-path Fourier transform infrared (OP/FT-IR)
      spectra of ammonia over wide concentration ranges.
AB  - The use of multiple calibration sets in partial least squares (PLS) regression
      was proposed to improve the quantitative determination of NH(3) over wide
      concentration ranges from open-path Fourier transform infrared (OP/FT-IR)
      spectra. The spectra were measured near animal farms, where the path-integrated
      concentration of NH(3) can fluctuate from nearly zero to as high as approximately
      1000 ppm-m. PLS regression with a single calibration set did not cover such a
      large concentration range effectively, and the quantitative accuracy was degraded
      due to the nonlinear relationship between concentration and absorbance for
      spectra measured at low resolution (1 cm(-1) and poorer.) In PLS regression with
      multiple calibration sets, each calibration set covers a part of the entire
      concentration range, which significantly decreases the serious nonlinearity
      problem in PLS regression occurring when only a single calibration set is used.
      The relative error was reduced from approximately 6% to below 2%, and the best
      results were obtained with four calibration sets, each covering one quarter of
      the entire concentration range. It was also found that it was possible to build
      the multiple calibration sets easily and efficiently without extra measurements.

PMID- 21740646
TI  - Pulmonary tuberculosis and risk factors in Portugal: a spatial analysis.
AB  - Tuberculosis (TB) is a multidimensional disease, and interactions between
      individuals and groups are of extreme importance in its development. The aim of
      this study was to estimate the occurrence of pulmonary TB (PTB) to identify
      potential risk factors and to define high-risk areas  in Portugal (2004-2006).
      The relevance of the common risk factors identified was evaluated at the national
      and local levels. Considering local public health at the municipality level, the
      main objective of this study was the support of local interventions, identifying
      local high-risk  areas and the corresponding local risk factors. A complex
      statistical methodology based on correlation analysis, spatial clustering, risk
      maps and multivariate regression models was developed. The results showed that
      some areas were at higher risk of PTB than others due to high incidence of 
      HIV/AIDS, incarceration, nonstandard (abnormal) and/or crowded accommodation,
      unemployment and immigrant populations. The majority of these areas showed
      increased TB incidence rates.

PMID- 21740647
TI  - A systematic review of economic evaluation studies of tuberculosis control in
      high-income countries.
AB  - Tuberculosis (TB) is a leading cause of death in developing countries and an
      important health threat in the industrialised world. Ideally, interventions in TB
      control are effective, acceptable and economically attractive. This review
      summarises all economic evaluation studies of TB control in high-income countries
      over the last 20 years. We provide indications on the relative economic
      attractiveness of TB interventions based on the reported conclusions. A total of
      118 studies using different economic evaluation methodologies on a wide range of
      TB interventions are included. Most studies (70%) were from North America, and
      about half (47%) concerned interventions among the general population. Even
      though the large majority of studies (85%) aimed at preventing active TB disease,
      44% of these ignored the prevention of secondary infections, thereby under-
      estimating the benefits of the intervention. Choosing a health care instead of a
      societal perspective (92% vs. 8%) further underestimated the benefits. Moreover,
      74 studies (62%) disregarded discounting, and for 9 of them this led to
      overestimated future costs. In all, 66% of the studies reported conclusions
      favouring the evaluated intervention, which is modest given that a publishing
      bias towards favourable results is to be expected. In conclusion, we demonstrate
      that many studies in this review have put the evaluated TB intervention at a
      disadvantage by the choice of methodology, i. e., underestimating benefits and
      overestimating costs. This may have led to an overly conservative approach to the
      introduction of new interventions in TB control.

PMID- 21740648
TI  - Characterization of chitosan-carboxymethyl dextran nanoparticles as a drug
      carrier and as a stimulator of mouse splenocytes.
AB  - The in vitro drug-release behavior of chitosan-carboxymethyl dextran
      nanoparticles (CDNP) containing cefmetazole, 5-fluorouracil (5-FU) or indocyanine
      green (ICG), and the in vitro effect of CDNP on mouse B16 melanoma cell
      proliferation and in vivo modulation effect of CDNP on serum cytokines and spleen
      lymphocytes in mice were evaluated in this study. Drug-loaded CDNP were prepared
      by embedding (for cefmetazole or 5-FU) and absorption (for ICG), and the particle
      size was increased with increased drug association efficiency (AE) and decreased
      surface amino group content. Prolonged release of cefmetazole (540 min) or 5-FU
      (360 min) from CDNP was observed when compared to that of nanoparticle-free
      cefmetazole (210 min) or 5-FU (50 min), and the release of cefmetazole or 5-FU
      from CDNP98 (CDNP made with 98% degree of deacetylation (DD) chitosan) was slower
      than from CDNP78 (CDNP made with 78% DD chitosan). High AE (72.0-98.6%),
      undetectable surface amino group content and dramatically increased particle size
      (1076.9-1506.0 nm) of ICG-loaded CDNP with undetectable release of ICG within 48
      h revealed the good affinity between ICG and CDNP. Twenty-five to 100 MUg/ml of
      CDNP elicited dose-dependent inhibitory effects on B16 tumor cell proliferation,
      and CDNP98 was more effective than CDNP78. CDNP78 regulated serum IL-17 level in
      up-regulating IL-4, IL-6, IL-10, IL-23 and TGF-beta within 3 h; on the other
      hand, CDNP98 significantly down-regulated TGF-beta and had no induction effect on
      IL-23 within 24 h. In addition, reduced IL-17 was observed in CDNP at 24 h.
      CDNP98 was more effective than CDNP78 in stimulating mouse splenic T CD4(+),
      TCD8(+) and NK cell proliferation within 24 h, while CDNP78 was superior to
      CDNP98 in stimulating B CD19(+) cells. The ability of CDNP to be the drug carrier
      and to enhance both humoral and cell-mediated immune response in this study
      demonstrated its promising potential to be applied as biomedical material. 

PMID- 21740649
TI  - The Union's Ethics Advisory Group.

PMID- 21740651
TI  - Why ethics matters in tuberculosis prevention, care and control.

PMID- 21740652
TI  - Tuberculosis: still a social disease.

PMID- 21740653
TI  - Ethical issues in tuberculosis diagnosis and treatment.
AB  - Drug-resistant tuberculosis (TB) has highlighted the need for discussion of
      ethical questions about TB diagnosis and treatment. Drug resistance is a human
      made phenomenon. It is caused by lack of patient adherence in drug taking and/or
      physician failure in prescription making. The global burden of TB is also partly
      explained by the lack of industry motivation to develop new TB drugs and
      diagnostics. This article explores the primary ethical issues associated with TB
      diagnosis and treatment: the human rights requirements regarding universal access
      to care and universal standards of care, treatment exclusion and cessation,
      privacy and stigmatisation in the context of directly observed therapy, and
      diagnostic challenges posed by limited laboratory capacity. Inter alia, it argues
      that: 1) the ethical imperative to improve individual patient care is partly
      based on the need to prevent the spread of infection and the exacerbation of the
      problem of drug resistance; 2) human rights and the imperative to protect the
      greater good of public health may call for increased regulation of the private
      sector; and 3) industry should be given further incentives to develop new tools
      for TB control.

PMID- 21740654
TI  - Health care provider obligations in caring for patients with tuberculosis.
AB  - It is well acknowledged that physicians and other health care providers have an
      obligation to provide clinical care to their patients even under occasionally
      difficult circumstances. However, the exact degree and extent of that obligation,
      and the various scenarios under which it might be lessened or even cease to
      exist, have recently become the focus of much discussion and debate. The reason
      for this emerging debate is twofold: the recent occurrence of pandemic viruses
      such as severe acute respiratory syndrome and H1N1, and the emergence of highly
      resistant strains of infectious pathogens such as multi and extensively drug
      resistant tuberculosis (TB). Health care providers have been asked to place
      themselves at risk to an extent many did not foresee when they chose to enter
      their profession, and many have done so under difficult conditions, often without
      adequate supplies and support. The present article explores the ethical
      obligations as well as the reciprocal rights of health care providers who are
      caring for patients with TB, with a particular focus on drug-resistant strains of
      the bacterium. It is a condensed version of a World Health Organization (WHO)
      Working Paper prepared for the WHO Working Group on Ethics and Tuberculosis.

PMID- 21740655
TI  - Public health measures to control tuberculosis in low-income countries: ethics
      and human rights considerations.
AB  - In low-income countries, tuberculosis (TB) control measures should be guided by
      ethical concerns and human rights obligations. Control programs should consider
      the principles of necessity, reasonableness and effectiveness of means,
      proportionality, distributive justice, and transparency. Certain measures
      detention, infection control, and treatment to prevent transmission-raise
      particular concerns. While isolation is appropriate under certain circumstances,
      quarantine is never an acceptable control measure for TB, and any detention must
      be limited by necessity and conducted humanely. States have a duty to implement
      hospital infection control to the extent of their available resources and to
      provide treatment to health care workers (HCWs) infected on the job. HCWs, in
      turn, have an obligation to provide care unless conditions are unreasonably and
      unforeseeably unsafe. Finally, states have an obligation to provide adequate
      access to treatment, as a means of preventing transmission, as broadly as
      possible and in a non-discriminatory fashion. Along with treatment, states should
      provide support to increase treatment adherence and retention with respect for
      patient privacy and autonomy. Compulsory treatment is almost never acceptable.
      Governments should take care to respect human rights and ethical obligations as
      they execute TB control programs.

PMID- 21740656
TI  - The ethics of clinical and epidemiological research.
AB  - The global burden of tuberculosis (TB) demands that research be undertaken. The
      vulnerability of the populations most at risk for TB demands that such research
      be subject to ethical review to protect their rights and interests. In this brief
      article we cannot review the vast and important literature bearing on the ethics
      of clinical and epidemiological research and public health surveillance. Instead,
      we have focused on three questions that have been at the center of discussion and
      debate and which have special relevance for TB. First, we examine a question that
      has special bearing when wealthy nations or international organizations carry out
      research in poor countries: what does justice require in the post trial period?
      Second, we examine the question of how the principles of consent and
      confidentiality may require modification in record-based epidemiological
      research. Third, we look at the challenges posed by public health surveillance,
      which in many cases requires case reporting by clinicians to public health
      agencies. By way of conclusion, we take note of the centrality of enhancing the
      institutional capacities for ethical review of research in poor nations.

PMID- 21740657
TI  - The social determinants of health: key to global tuberculosis control.
AB  - Improved tuberculosis (TB) diagnosis and treatment through the DOTS and Stop TB
      strategies have saved millions of lives; however, their impact on TB incidence
      has been disappointing and the scale of the epidemic remains overwhelming. To
      reduce the incidence of TB, the drivers of the epidemic and social determinants
      of TB need to be addressed. These include co-morbidities and substance use and,
      moreover, the social and economic conditions that determine both the course of
      the TB epidemic and exposure to these risk factors. Doing so builds on the
      history of TB prevention and treatment during the public health revolution that
      resulted in a dramatic reduction in incidence in many countries. Addressing the
      social determinants is also imperative to address pervasive inequities in the
      incidence, mortality and morbidity of TB between different population groups,
      including in the performance of health systems in delivering diagnostic and
      treatment interventions, and in the financial consequences of people seeking
      care. Action on the social determinants can be categorised in terms of health
      sector interventions, intersectoral policies impacting across society, and
      measurement and research to better understand inequities and links between TB and
      other factors. TB programmes cannot carry out these actions alone; however, they
      can make important contributions in the delivery of interventions and in
      advocating and negotiating for intersectoral efforts. The considerable progress
      seen in the clinical care of TB needs to be sustained; however, the attainment of
      TB targets, including elimination by 2050, will require expansion of the lens of
      TB control efforts beyond 'business as usual' to address the social determinants
      of the disease.

PMID- 21740658
TI  - Cash transfer and microfinance interventions for tuberculosis control: review of
      the impact evidence and policy implications.
AB  - OBJECTIVE: To quantify the impact of cash transfer and microfinance interventions
      on a selected list of tuberculosis (TB) risk factors and assess their potential
      role in supporting TB control. DATA SOURCE: Published and unpublished references
      identified from clinical and social electronic databases, grey literature and web
      sites. METHODS: Eligible interventions had to be conducted in middle- or low
      income countries and document an impact evaluation on any of the following
      outcomes: 1) TB or other respiratory infections; 2) household socio-economic
      position; and 3) factors mediating the association between low household socio
      economic position and TB, including inadequate health-seeking behaviours, food
      insecurity and biological TB risk factors such as human immunodeficiency virus
      (HIV) and adult malnutrition. Interventions targeting special populations were
      excluded. RESULTS: Fifteen cash transfer schemes (four unconditional and 11
      conditional) and seven microfinance programmes met the eligibility criteria. No
      intervention addressed TB or any other respiratory infection. Of 11 cash transfer
      and four microfinance interventions, respectively seven and four reported a
      positive impact on indicators of economic well-being. A positive impact on
      household food security was documented in respectively eight of nine and three of
      five cash transfer and microfinance interventions. Improved health care access
      was documented respectively in 10 of 12 cash transfer and four of five
      microfinance interventions. The only intervention evaluating impact on HIV
      incidence was a microfinance project that found no effect. No cash transfer or
      microfinance interventions had an impact on adult malnutrition. CONCLUSIONS: Cash
      transfer and microfinance interventions can positively impact TB risk factors.
      Evaluation studies are urgently needed to assess the impact of these social
      protection interventions on actual TB indicators.

PMID- 21740659
TI  - The Innovative Socio-economic Interventions Against Tuberculosis (ISIAT) project:
      an operational assessment.
AB  - SETTING: Tuberculosis (TB) affected households in impoverished shantytowns, Lima,
      Peru. OBJECTIVE: To evaluate socio-economic interventions for strengthening TB
      control by improving uptake of TB care and prevention services. DESIGN: Barriers
      to TB control were characterised by interviews with TB-affected families. To
      reduce these barriers, a multidisciplinary team offered integrated community and
      household socio-economic interventions aiming to: 1) enhance uptake of TB care by
      education, community mobilisation and psychosocial support; and 2) reduce poverty
      through food and cash transfers, microcredit, microenterprise and vocational
      training. An interim analysis was performed after the socio-economic
      interventions had been provided for 2078 people in 311 households of newly
      diagnosed TB patients for up to 34 months. RESULTS: Poverty (46% earned <US$1 per
      day), depression (40%), stigmatisation (77%), and perceived isolation (39%) were
      common among TB patients (all P < 0.05 vs. non-patients). The project had 100%
      recruitment, and involved 97% of TB-affected households in regular visits, 71% in
      community groups, 78% in psychosocial support and 77% in poverty-reduction
      interventions. The socio-economic interventions were associated with increases in
      household contact TB screening (from 82% to 96%); successful TB treatment
      completion (from 91% to 97%); patient human immunodeficiency virus testing (from
      31% to 97%); and completion of preventive therapy (from 27% to 87%; all P <
      0.0001). CONCLUSIONS: Socio-economic interventions can strengthen TB control
      activities. KEYWORDS: tuberculosis; control; microcredit; poverty;social
      determinants.

PMID- 21740660
TI  - Measuring socio-economic data in tuberculosis prevalence surveys.
AB  - Addressing social determinants in the field of tuberculosis (TB) has received
      great attention in the past years, mainly due to the fact that worldwide TB
      incidence has not declined as much as expected, despite highly curative control
      strategies. One of the objectives of the World Health Organization Global Task
      Force on TB Impact Measurement is to assess the prevalence of TB disease in 22
      high-burden countries by active screening of a random sample of the general
      population. These surveys provide a unique opportunity to assess socio-economic
      determinants in relation to prevalent TB and its risk factors. This article
      describes methods of measuring the socio-economic position in the context of a TB
      prevalence survey. An indirect measurement using an assets score is the most
      feasible way of doing this. Several examples are given from recently conducted
      prevalence surveys of the use of an assets score, its construction, and the
      analyses of the obtained data.

PMID- 21740661
TI  - Modeling social, environmental and biological determinants of tuberculosis.
AB  - Mathematical models have facilitated our understanding of infectious diseases
      dynamics and proved useful tools to compare control scenarios when interventional
      studies are not feasible or ethical. Here, we summarize evidence linking social,
      economic and biologic determinants to tuberculosis (TB) and review modeling
      approaches that have been used to understand their contribution to the epidemic
      dynamics of TB. Specifically, we find evidence for associations between smoking,
      indoor air pollution, diabetes mellitus, alcohol, nutritional status, crowding,
      migration, aging and economic trends, and the occurrence of TB infection and/or
      disease. We outline some methodological problems inherent to the study of these
      associations; these include study design issues, reverse causality and
      misclassification of both exposure and outcomes. We then go on to review two
      existing approaches to modeling the impact of determinants and the effect of
      interventions: the population attributable fraction model, which estimates the
      proportion of the TB burden that would be averted if exposure to a risk factor
      were eliminated from the population, and deterministic epidemic models that
      capture transmission dynamics and the indirect effects of interventions. We
      conclude by defining research priorities in both the study of specific
      determinants and the development of appropriate models to assess the impact of
      addressing these determinants.

PMID- 21740662
TI  - Predictors of developing acute respiratory distress syndrome in patients with
      miliary tuberculosis.

PMID- 21740663
TI  - A modelling framework to support the selection and implementation of new
      tuberculosis diagnostic tools.
AB  - Efforts to stimulate technological innovation in the diagnosis of tuberculosis
      (TB) have resulted in the recent introduction of several novel diagnostic tools.
      As these products come to market, policy makers must make difficult decisions
      about which of the available tools to implement. This choice should depend not
      only on the test characteristics (e.g., sensitivity and specificity) of the
      tools, but also on how they will be used within the existing health care
      infrastructure. Accordingly, policy makers choosing between diagnostic strategies
      must decide: 1) What is the best combination of tools to select? 2)Who should be
      tested with the new tools? and 3)Will these tools complement or replace existing
      diagnostics? The best choice of diagnostic strategy will likely vary between
      settings with different epidemiology (e.g., levels of TB incidence, human
      immunodeficiency virus co-infection and drug-resistant TB) and structural and
      resource constraints (e.g., existing diagnostic pathways, human resources and
      laboratory capacity). We propose a joint modelling framework that includes a
      tuberculosis (TB) transmission component (a dynamic epidemiological model) and a
      health system component (an operational systems model) to support diagnostic
      strategy decisions. This modelling approach captures the complex feedback loops
      in this system: new diagnostic strategies alter the demands on and performance of
      health systems that impact TB transmission dynamics which, in turn, result in
      further changes to demands on the health system. We demonstrate the use of a
      simplified model to support the rational choice of a diagnostic strategy based on
      health systems requirements, patient outcomes and population-level TB impact.

PMID- 21740664
TI  - Historical research into tuberculosis control strategies and the implications of
      mortality trends in Taiwan.
AB  - SETTING: Taiwan. OBJECTIVE: To analyse mortality trends to determine whether
      government organisation structuring and activities of disease control programmes
      affect outcomes. DESIGN: We conducted a Joinpoint regression analysis to identify
      changes in TB mortality trends from 1971 to 2008 in Taiwan. The annual percentage
      change (APC) was calculated for the time segments on either side of the
      Joinpoints. Mortality data were extracted from the cause-of-death registry
      database of the Taiwanese Department of Health. RESULTS: Between 1971 and 1987,
      the TB mortality rate dropped from 51 per 100 000 population to 13.4/100 000;
      during the period 1987-2000, it dropped from 13.4 to 7/100 000, with a lower APC;
      and from 2000 to 2008, it fell more rapidly, from 7 to 2.2/100 000, than during
      the previous two stages. These turning points are associated with organisational
      structure changes from the Joinpoint regression analysis. CONCLUSION: We found
      that organisational structure and availability of resources play an important
      role in TB control. We recommend that other countries consider these vital
      factors to enhance the effectiveness of their TB control programmes.

PMID- 21740665
TI  - Capture-recapture to estimate completeness of tuberculosis surveillance in two
      communities in South Africa.
AB  - BACKGROUND: Reliable surveillance is essential for any tuberculosis (TB) control
      programme; however, under-registration of TB cases due to under-notification of
      patients on treatment or failure to initiate treatment has been well-documented
      internationally. OBJECTIVE: To determine the contribution of capture-recapture
      methods in estimating the completeness of bacteriologically confirmed pulmonary
      TB registration in two high-incident communities in South Africa. METHODS: Record
      linkage between the TB treatment register and two laboratory sputum TB result
      registers and three-source log-linear capture-recapture analysis. RESULTS: The
      number of bacteriologically confirmed pulmonary TB cases in the TB treatment
      register was 243, with an additional 63 cases identified in the two laboratory
      databases, resulting in 306 TB cases. The observed completeness of the TB
      treatment register was 79%. The log-linear model estimated 326 (95%CI 314-355) TB
      cases, resulting in an estimated completeness of registration of 75% (95%CI 68
      77). CONCLUSION: Capture-recapture can be useful in evaluating the completeness
      of TB control surveillance and registration, including in resource-limited
      settings; however, methodology and results should be carefully assessed.
      Interventions are needed to increase the completeness of registration and to
      reduce the number of initial defaulters.

PMID- 21740666
TI  - Missed opportunities to prevent tuberculosis in foreign-born persons,
      Connecticut, 2005-2008.
AB  - SETTING: Factors that influence testing for latent tuberculosis infection (LTBI)
      among foreign-born persons in Connecticut are not well understood. OBJECTIVE: To
      identify predictors for LTBI testing and challenges related to accessing health
      care among the foreign-born population in Connecticut. DESIGN: Foreign-born
      Connecticut residents with confirmed or suspected tuberculosis (TB) disease
      during June 2005-December 2008 were interviewed regarding health care access and
      immigration status. Predictors for self-reported testing for LTBI after US entry
      were determined. RESULTS: Of 161 foreign-born persons interviewed, 48%
      experienced TB disease within 5 years after arrival. One third (51/156) reported
      having undergone post-arrival testing for LTBI. Although those with established
      health care providers were more likely to have reported testing (aOR 4.49, 95%CI
      1.48-13.62), only 43% of such persons were tested. Undocumented persons, the
      majority of whom lacked a provider (53%), were less likely than documented
      persons to have reported testing (aOR 0.20, 95%CI 0.06-0.67). Hispanic permanent
      residents (immigrants and refugees) and visitors (persons admitted temporarily)
      were more likely than non-Hispanics in the respective groups to have reported
      testing (OR 5.25, 95%CI 1.51-18.31 and OR 7.08, 95%CI 1.30-38.44, respectively).
      CONCLUSIONS: The self-reported rate of testing for LTBI among foreign-born
      persons in Connecticut with confirmed or suspected TB was low and differed
      significantly by ethnicity and immigration status. Strategies are needed to
      improve health care access for foreign-born persons and expand testing for LTBI,
      especially among non-Hispanic and undocumented populations.

PMID- 21740667
TI  - Housekeeping health care workers have the highest risk for tuberculin skin test
      conversion.
AB  - BACKGROUND: Not all health care workers (HCWs) are at the same risk for
      tuberculin skin test (TST) conversion, indicating latent tuberculosis (TB)
      infection. OBJECTIVE: To identify risk factors for TST conversion among HCWs.
      METHODS: A retrospective cohort study conducted at a tertiary university medical
      centre included every HCW who had had a negative two-step TST at work entry and
      at least one consecutive TST in the period 2005-2009 (mean follow-up period 55
      months). Binomic logistic regression analysis was used to identify risk factors
      for TST conversion. Potential risk factors such as age, health care profession,
      patient exposure profile, workplace division and history of bacille Calmette
      Guerin vaccination were entered in the model. RESULTS: A total of 450 subjects
      met the inclusion criteria, of whom 93 had TST conversion. The highest annual
      rates of TST conversion occurred in workers who worked as housekeeping staff
      (6.9%). Older age, a work environment with high patient turnover and employment
      in maintenance departments were significant risk factors (adjusted odds ratios
      2.05, 5.2 and 8.4 respectively). CONCLUSION: Housekeeping staff, older age
      workers and health care professionals working in an environment of high patient
      turnover are at increased risk for latent TB infection.

PMID- 21740668
TI  - Predictors of discordant tuberculin skin test and QuantiFERON(r)-TB Gold In-Tube
      results in various high-risk groups.
AB  - SETTING: Persons in whom targeted testing for latent tuberculosis infection
      (LTBI) is recommended in Seattle, Washington; Atlanta, Georgia; and central North
      Carolina, United States. OBJECTIVE: To compare the performance of an interferon
      gamma release assay (QuantiFERON(r)-TB Gold In-Tube [QFT-GIT]) with the
      tuberculin skin test (TST) among foreign-born, homeless, human immunodeficiency
      virus (HIV) infected and substance abuse persons tested for LTBI. DESIGN: A cross
      sectional study requiring participants to have a blood test, a TST and data
      collected. RESULTS: Of 1653 persons, 19.5% were TST-positive and 14.0% were QFT
      GIT-positive. Overall concordance was moderate (kappa 0.53; 95%CI 0.47-0.58).
      Compared to concordant positive results, TST+/QFT-GIT- discordance was associated
      with HIV infection and sex, while TST-/QFT-GIT+ discordance was associated with
      HIV and inversely associated with foreign birth. Compared to concordant negative
      results, TST-/QFT-GIT+ discordance was associated with foreign birth and age >=50
      years, while TST+/QFT-GIT-discordance was associated with foreign birth, age 30
      49 years, being Black and inversely associated with HIV. HIV infection was
      significantly associated with indeterminate QFT-GIT results. CONCLUSION: QFT-GIT
      may be an improvement over the TST for diagnosing LTBI in foreign-born and older
      persons, and may be as useful as the TST in HIV-infected persons. The sensitivity
      of both tests may be low in HIV-infected persons.

PMID- 21740669
TI  - Is the delay in diagnosis of pulmonary tuberculosis related to exposure to
      fluoroquinolones or any antibiotic?
AB  - BACKGROUND: Delays in diagnosis of tuberculosis (TB) have been associated with
      previous use of antibiotics, and in particular fluoroquinolones (FQ), for
      suspected pulmonary infections. METHODS: We conducted a population-based cohort
      study with 2232 patients who had active TB between 1997 and 2006 (records
      obtained from the British Columbia Linked Health Databases). Patients with a
      record of an initial health care contact preceding the diagnosis of TB were
      identified for inclusion. Health care delay was defined as the time between
      initial health care contact and the initiation of anti-tuberculosis medication,
      and was compared between patients prescribed antibiotics and those not exposed to
      any antibiotics. RESULTS: A total of 1544 patients were included. After adjusting
      for covariates, average health care delay for patients exposed to antibiotics was
      found to be significantly greater, by a factor of 2.10 (95%CI 1.80-2.44), with a
      median delay of 41 days in the antibiotic group compared to 14 days in the non
      antibiotic group. Sex, age, foreign-born status and socio-economic status were
      non-significant factors. Health care delay increased with the number of
      antibiotic courses received, but not with the type of antibiotic. CONCLUSIONS:
      Previous treatment with any antibiotic, and not only a FQ, is associated with a
      delay in TB diagnosis.

PMID- 21740670
TI  - Consulting private health care providers aggravates treatment delay in urban
      South African tuberculosis patients.
AB  - SETTING: An urban primary health care facility in Khayelitsha, South Africa.
      OBJECTIVES: To determine the difference in total tuberculosis (TB) treatment
      delay in patients who initially seek care at National TB Control Programme (NTP)
      facilities after the onset of TB-related symptoms, compared to patients who
      initially seek care from non-NTP health care practitioners (HCP); and to describe
      the relative contributions of diagnostic, treatment initiation, patient and
      health system (HS) delay. DESIGN: A cross-sectional study of adult TB patients
      treated by the NTP. RESULTS: A total of 210 patients (median age 31 years) were
      enrolled from May to December 2009: 46% were male, and 58% were human
      immunodeficiency virus (HIV) infected. The median duration of total delay was 31
      days, diagnostic delay 26, treatment initiation delay 0, patient delay 8 and HS
      delay 17 days. Initial visit to a non-NTP HCP was independently associated with
      total (P = 0.007), HS (P = 0.014) and diagnostic delays (P = 0.012). HIV
      infection was an independent risk factor for total (P = 0.047) and HS delay (P =
      0.021); 27% of patients reported first going to a non-NTP HCP. CONCLUSION:
      Initial care sought from non-NTP HCP was the main determinant of total, HS and
      diagnostic delays. Engagement and education of private HCPs is recommended.

PMID- 21740671
TI  - Quality of induced sputum using a human-powered nebuliser in a mobile human
      immunodeficiency virus testing service in South Africa.
AB  - OBJECTIVES: To investigate the quality of induced sputum samples using a human
      powered (HPN) and an electric-powered nebuliser (EPN). METHODS: For each
      participant two sputum samples were induced using the HPN and the EPN. The
      sequence of the two nebulisers was allocated at random. The proportion of good
      quality sputum according to different assessment criteria was compared using an
      exact McNemar test. The difference in time to expectoration was compared using
      the Wilcoxon matched-pairs signed-rank test. RESULTS: A total of 123 individuals
      were eligible for the study. Nine individuals refused to participate and five
      were unable to produce a sputum sample. The proportion of good quality sputum was
      higher among sputum samples induced by the HPN compared to those obtained using
      the EPN. The median time to produce a sputum sample was 2.2 min (IQR 1.13-4.1)
      for the HPN and 2.5 min (IQR 1.4-4.1) for the EPN. CONCLUSION: The HPN induced
      good quality sputum within 3 min. The device operates without electricity and is
      suitable not only for remote clinics with unreliable electricity, but also for
      mobile services and community-based intensified tuberculosis (TB) case finding.
      Further research needs to investigate the yield of TB in sputum samples induced
      by the HPN.

PMID- 21740672
TI  - Tuberculosis in human immunodeficiency virus infected Ugandan children starting
      on antiretroviral therapy.
AB  - OBJECTIVE: To identify the incidence of tuberculosis (TB) in human
      immunodeficiency virus (HIV) infected children in a resource-limited setting
      before and after initiation of antiretroviral therapy (ART), and to assess the
      impact of TB screening by tuberculin skin testing and clinical history. METHODS:
      A retrospective cohort study of 1806 HIV-infected children and adolescents (age
      <18 years) initiating ART from 2003 to 1 July 2006 in Kampala, Uganda. A TB
      screening program was instituted clinic-wide in January 2006. RESULTS: Of 311
      (17.2%) HIV-infected children, 171 had been diagnosed with TB before and 140
      after ART initiation. During the first 100 days of ART, risk of a new TB
      diagnosis was 2.7-fold higher compared to the pre-ART period (RR 2.7, 95%CI 2.1
      3.5, P < 0.001). After 100 days of ART, the TB incidence rate decreased to below
      pre-ART levels (RR 0.41, 95%CI 0.30-0.54, P = 0.002). After TB screening was
      instituted in 2006, the proportion of new TB cases diagnosed after starting ART
      decreased by 70% (95%CI 51-82, P < 0.001), abating the early excess risk.
      CONCLUSIONS: TB is common among African children and adolescents initiating ART
      in sub-Saharan Africa. More aggressive screening for active TB before starting
      ART can diminish the rate of TB during immune reconstitution. Future studies are
      needed to determine optimal screening practices for HIV-infected children.

PMID- 21740673
TI  - Disseminated tuberculosis in human immunodeficiency virus infection: ineffective
      immunity, polyclonal disease and high mortality.
AB  - BACKGROUND: Disseminated tuberculosis (TB) is a major cause of death in patients
      with the acquired immune-deficiency syndrome (AIDS), but its pathogenesis and
      clinical features have not been defined prospectively. METHODS: Human
      immunodeficiency virus (HIV) infected adults with a CD4 count >= 200 cells/MUl
      and bacille Calmette-Guerin scar underwent immunologic evaluation and subsequent
      follow-up. RESULTS: Among 20 subjects who developed disseminated TB, baseline
      tuberculin skin tests were >=15 mm in 14 (70%) and lymphocyte proliferative
      responses to Mycobacterium tuberculosis were positive in 14 (70%). At the time of
      diagnosis, fever >=2 weeks plus >=5 kg weight loss was reported in 16 (80%)
      patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10
      (50%); median CD4 count was 30 cells/MUl (range 1-122). By insertion sequence
      (IS) 6110 analysis, 14 (70%) blood isolates were clustered and 3/8 (37%)
      concurrent sputum isolates represented a different strain (polyclonal disease).
      Empiric TB treatment was given to eight (40%) patients; 11 (55%) died within a
      month. CONCLUSIONS: Disseminated TB in HIV occurs with cellular immune responses
      indicating prior mycobacterial infection, and IS6110 analysis suggests an often
      lethal combination of reactivation and newly acquired infection. Control will
      require effective prevention of both remotely and recently acquired infection,
      and wider use of empiric therapy in patients with advanced AIDS and prolonged
      fever.

PMID- 21740674
TI  - Bronchial artery embolisation for the management of haemoptysis in patients with
      pulmonary tuberculosis.
AB  - OBJECTIVES: To evaluate immediate and long-term outcomes of bronchial artery
      embolisation (BAE) for the treatment of haemoptysis in patients with pulmonary
      tuberculosis (TB), and to clarify factors that influence recurrence. DESIGN: Of
      398 patients with haemoptysis who underwent BAE between January 2004 and June
      2009, 169 were retrospectively reviewed. All of the patients had either a history
      of pulmonary TB or a current diagnosis of TB. Follow-up ranged from 1 day to 66
      months. RESULTS: Haemoptysis was stopped or markedly decreased, with subsequent
      clinical improvement, in 163 patients (96.4%); in 50 patients symptoms recurred
      during the follow-up period. Disease activity, aortography and mycetoma showed a
      statistically significant correlation with recurrence rate. Cumulative non
      recurrence rates were 76.1% for 12 months and 51.4% for 40 months. The median non
      recurrence time was 41.2 months. Disease activity and mycetoma showed a
      statistically significant correlation with early recurrence. Only one major
      complication was observed. CONCLUSIONS: BAE is a safe and effective treatment
      option for the control of haemoptysis in TB patients. Disease activity and
      mycetoma both correlate with higher recurrence rate and early time of recurrence.

PMID- 21740675
TI  - Acute respiratory distress syndrome caused by miliary tuberculosis: a multicentre
      survey in South Korea.
AB  - BACKGROUND: Miliary tuberculosis (TB) is an unusual cause of acute respiratory
      distress syndrome (ARDS). OBJECTIVE: To evaluate the clinical characteristics and
      outcomes of patients with ARDS caused by miliary TB admitted to the intensive
      care unit (ICU). DESIGN: A total of 67 patients were enrolled during the period
      1999-2008. RESULTS: The median age of the patients was 56 years (range 17-81), 19
      (28.4%) were aged >71 years, and 38 (56.7%) were male. All-cause mortality in the
      ICU and hospital were respectively 58.2% and 61.2%. Of the total number of
      enrolled patients, 49 (73.1%) were prescribed anti-tuberculosis medication within
      3 days of hospital admission. On the day of ARDS diagnosis (10.0 +/- 3.7 vs. 7.4
      +/- 3.5, P = 0.005), non-survivors had a significantly higher Sequential Organ
      Failure Assessment (SOFA) score than survivors. Multivariate analysis showed that
      SOFA score on the day of ARDS diagnosis was a significant predictor of survival
      (OR 0.809, 95%CI 0.691-0.946, P = 0.008). It was difficult to determine the
      efficacy of systemic corticosteroids on patient survival. CONCLUSION: ARDS caused
      by miliary TB was associated with a high in-hospital mortality rate, with SOFA
      score on the day of ARDS diagnosis being a valuable prognostic indicator.

PMID- 21740676
TI  - Different therapeutic responses in chronic obstructive pulmonary disease
      subgroups.
AB  - SETTING: Eleven referring hospitals in South Korea. OBJECTIVE: To compare
      therapeutic responses in chronic obstructive pulmonary disease (COPD) subgroups,
      classified by diffusing capacity of the lung for carbon monoxide (DL(CO)) and
      lung volume. DESIGN: A total of 130 stable male COPD patients were classified
      into four subgroups according to baseline DL(CO) and residual volume/total lung
      capacity (RV/TLC) ratio. We compared therapeutic responses to short acting
      beta(2)-agonist (SABA) and 3-month combined inhalation of long-acting beta(2)
      agonist (LABA) and corticosteroid among patients with these subgroups. RESULTS:
      Among the 130 COPD patients, 41 (31.5%) had normal DL(CO) and RV/TLC, 28 (21.5%)
      low DL(CO) and normal RV/TLC, 31 (23.8%) normal DL(CO) and high RV/TLC, and 30
      (23.1%) low DL(CO) and high RV/TLC. The normal DL(CO)/high RV/TLC subgroup showed
      a significantly larger flow response (changes in forced expiratory volume in 1 s)
      to salbutamol than the normal DL(CO)/RV/TLC subgroups, and a larger volume
      response (changes in forced vital capacity) than the two normal RV/TLC subgroups.
      The normal DL(CO)/high RV/TLC subgroup also showed significantly larger flow and
      volume response to 3-month combined inhalation of LABA and corticosteroid than
      the two normal RV/TLC subgroups. CONCLUSION: COPD subgroups classified by DL(CO)
      and RV/TLC may have different pulmonary function responses to pharmacological
      treatment.

PMID- 21740677
TI  - The impact of combined pulmonary fibrosis and emphysema on mortality.
AB  - SETTING: The impact on patient mortality of combined pulmonary fibrosis and
      emphysema (CPFE) compared with emphysema alone has never been investigated.
      OBJECTIVE: To elucidate whether CPFE has an impact on overall mortality over that
      of emphysema alone. DESIGN: We screened patients who underwent chest computed
      tomography (CT) scans during the period from 1 January 2001 to 31 December 2005
      in a tertiary referral hospital. Patients who had both emphysema and pulmonary
      fibrosis, thus meeting the inclusion criteria, were defined as CPFE. Controls
      with emphysema alone who were matched for age, sex and the date of CT scan were
      randomly selected. Cox proportional regression analysis was performed to verify
      whether CPFE is associated with increased overall mortality. RESULTS: We found
      135 CPFE cases. In the multivariable Cox regression stratified by the presence of
      comorbid malignancy, CPFE had five times higher mortality risk (adjusted HR 5.10,
      95%CI 1.75-14.9) in non-malignant cases, and showed a statistically insignificant
      trend for higher mortality risk (adjusted HR 1.70, 95%CI 0.94-2.51) in the
      malignant cases after adjusting for forced vital capacity, height and
      hypertension. CONCLUSION: CPFE is not rare and CPFE patients had a higher overall
      mortality risk than emphysema-only patients.

PMID- 21740678
TI  - Lung cancer mortality in Spain: estimating the future burden to the year 2028.
AB  - OBJECTIVE: To use lung cancer mortality rates from 1979 to 2008 in Andalusia,
      southern Spain (population >8,000,000), to provide an estimate of the future
      number of deaths for the period 2009-2028. DESIGN: The numbers of lung cancer
      deaths from 1979 to 2008 were obtained from the Andalusian Institute for
      Statistics (AIS). Data were arranged in 5-year age groups using an age-period
      cohort model. Age-standardised rates (ASR) per 100, 000 were calculated for males
      and females. Population projections for Andalusia 2009-2028 were downloaded from
      the AIS database. RESULTS: In males, the ASR varied from 46.1 in 2004-2008 to
      34.6 in 2024-2028, with a projected 33% decrease. In females, the ASR varied from
      4.9 in 2004-2008 to 8.9 per 100,000 in 2024-2028, with a projected 45% increase.
      This reflects an annual change of -1.3% for males and of +2.7% for females for
      the period 2009-2028. The sex ratio is projected to drop from a male:female ratio
      of 11 (1979-1983) to 3.8 (2024-2028). CONCLUSIONS: Our projections emphasise the
      significance of a continuously increasing trend in female lung cancer mortality,
      with a drop in the projected sex ratio.

PMID- 21740679
TI  - Smoking habits and attitudes toward tobacco bans among United Kingdom hospital
      staff and students.
AB  - SETTING: A group of United Kingdom (UK) hospitals. OBJECTIVE: To estimate the
      current smoking habits of health care professionals (HCPs) in a country with
      active tobacco control measures, and to record their attitudes to national and
      hospital tobacco bans. DESIGN: A cross-sectional survey of 500 HCPs. RESULTS:
      HCPs reported a lower rate of current smoking (7%) than the general population
      (24%). Doctors (2.6%) and medical students (3.8%) were less likely to be current
      smokers than both nurses (8.7%) and allied health professionals (10.9%, P <
      0.001). The vast majority felt national legislation had been effective (88%) and
      well complied with (82%). Around a third of respondents believed the ban had led
      to a reduction in admissions for acute coronary syndrome. Almost all respondents
      were in favour of restrictions on smoking in health care premises. A higher
      proportion of UK doctors (69%) than nurses (52%) favoured a complete ban (odds
      ratio 2.01, 95% confidence interval 1.14-3.56). CONCLUSION: Self-reported smoking
      patterns in UK health professionals are lower than previously and compared to
      other industrialised and developing countries. Support for bans is very high, but
      differences remain in behaviour and especially attitudes to local bans according
      to professional status, although this gap is also narrowing.

PMID- 21740680
TI  - Translating childhood tuberculosis case management research into operational
      policies.
AB  - The control of childhood tuberculosis (TB) has been of low priority in TB
      programmes in high-burden settings. The objective of this paper was to describe
      the development and testing of tools for the management of childhood TB. The
      Pakistan National TB Control Programme embarked on a number of activities,
      including the establishment of policy guidelines for the management of childhood
      TB and later a guidance document, 'Case Management Desk Guide and Structured
      Monitoring', to demonstrate the implementation of childhood TB interventions in a
      programme context. Initial results showed improved case finding and treatment
      outcome in implementation sites compared with control districts. However, further
      programme attention is required to improve quality.

PMID- 21740681
TI  - Primary Mycobacterium bovis infection revealed by erythema nodosum.
AB  - Mycobacterium bovis is responsible for a zoonosis originating in cattle. This
      disease has rarely affected man in industrialised countries since the
      establishment of veterinary surveillance in cattle. We report the case of a young
      female patient who developed a Mycobacterium bovis primary infection revealed by
      erythema nodosum. Infection was probably due to the consumption of non
      pasteurised milk in Morocco. This clinical manifestation is rare and physicians
      ought to be aware of this imported pathology.

PMID- 21740682
TI  - Vitamin D deficiency in adult tuberculosis patients.

PMID- 21740683
TI  - High-dose rifampicin: how do we proceed?

PMID- 21740684
TI  - Early diagnosis of female genital tuberculosis by laparoscopy and endometrial
      polymerase chain reaction.

PMID- 21740685
TI  - The pathophysiology of pulmonary edema caused by inflammation.

PMID- 21740688
TI  - Validation of a liquid chromatography-tandem mass spectrometry method for the
      detection of nicotine biomarkers in hair and an evaluation of wash procedures for
      removal of environmental nicotine.
AB  - The aim of this exploratory study was to develop and validate a liquid
      chromatography-tandem mass spectrometry (LC-MS-MS) method for the quantification
      of nicotine, eight nicotine metabolites, and two minor tobacco alkaloids in
      fortified analyte-free hair and subsequently apply this method to hair samples
      collected from active smokers. An additional aim of the study was to include an
      evaluation of different wash procedures for the effective removal of
      environmentally deposited nicotine from tobacco smoke. An apparatus was designed
      for the purpose of exposing analyte-free hair to environmental tobacco smoke in
      order to deposit nicotine onto the hair surface. A shampoo/water wash procedure
      was identified as the most effective means of removing nicotine. This wash
      procedure was utilized for a comparison of washed and unwashed heavy smoker hair
      samples. Analytes and corresponding deuterated internal standards were extracted
      using a cation-exchange solid-phase cartridge. LC-MS-MS was carried out using an
      AcquityTM UPLC((r)) system (Waters) and a Quattro Premier XETM triple quadrupole
      MS (Waters) operated in electrospray positive ionization mode, with multiple
      reaction monitoring data acquisition. The developed method was applied to hair
      samples collected from heavy smokers (n = 3) and low-level smokers (n = 3)
      collected through IRB-approved protocols. Nicotine, cotinine, and nornicotine
      were quantified in both the washed and unwashed hair samples collected from three
      heavy smokers, whereas 3-hydroxycotinine was quantified in only one unwashed
      sample and nicotine-1'-oxide in the washed and unwashed hair samples from two
      heavy smokers. In contrast, nicotine-1'-oxide was quantified in one of the three
      low-level smoker samples; nicotine was quantified in the other two low-level
      smoker samples. No other analytes were detected in the hair of the three low
      level smokers.

PMID- 21740689
TI  - Zinc reduces the detection of cocaine, methamphetamine, and THC by ELISA urine
      testing.
AB  - Federal workplace drug testing was initiated during the late 1980s. Since then,
      numerous methods have been employed to subvert these drug tests, adulteration of
      urine samples being the most common. A wide variety of adulterants has been
      reported to date along with suitable methods of their detection. Recently,
      websites have claimed that zinc sulfate can be an effective adulterant to bypass
      drug testing. Herein, these claims are investigated using standard drug detection
      kits and urine samples adulterated with zinc. Drug-free urine samples were
      fortified with different amounts methamphetamines and benzoylecgonine, to which
      zinc sulfate was added to study its effect. Urine samples from acute marijuana
      smokers were also obtained in order to study the effects of zinc supplements on
      THC drug testing. All urine drug testing was performed using ELISA detection kits
      manufactured by Immunalysis. Both zinc sulfate and zinc supplements are effective
      in interfering with the detection of all three drugs by Immunalysis drug
      detection kits. Also, no suitable method could be established to detect zinc in
      urine samples. Zinc can be an effective adulterant in urine for some illicit
      drugs that are commonly screened under routine drug testing.

PMID- 21740690
TI  - Determination of L-ephedrine, pseudoephedrine, and caffeine in rat plasma by
      liquid chromatography-tandem mass spectrometry.
AB  - A rapid and simple liquid chromatography tandem mass spectrometry method was
      developed and validated for the simultaneous determination of L-ephedrine,
      pseudoephedrine, and caffeine in male Fisher-344 rat plasma at nanogram-per
      milliliter concentrations for use in support of toxicology studies. Only 25 MUL
      of plasma is required, and extraction is performed using a simple, single-step
      protein precipitation. The method was validated over a range of 2.09 to 5460
      ng/mL for L-ephedrine, 2.09 to 5050 ng/mL for pseudoephedrine and 2.03 to 5340
      ng/mL for caffeine. A binary gradient elution at 0.3 mL/min was used with a
      Waters XBridge Phenyl (2.1 * 150 mm, 3.5 MUm) column and a Waters XBridge Phenyl
      2.1- * 10-mm guard column at ambient temperature. The mobile phase consisted of
      10 mM ammonium acetate in water (pH 5.0) and methanol. Caffeine trimethyl
      (13)C(3) was used as the internal standard. The method was evaluated for
      linearity, recovery, precision, accuracy, and stability, and it was successfully
      applied in toxicokinetic studies of ephedrine, administered alone, in combination
      with caffeine, and in the herbal source Ma Huang.

PMID- 21740691
TI  - Benzodiazepine whole blood concentrations in cases with positive oral fluid on
      site screening test results using the DrugWipe((r)) single for benzodiazepines.
AB  - Reliable on-site oral fluid screening devices are a useful and convenient means
      of policing traffic. In Finland, benzodiazepines represent a particular challenge
      to traffic safety. This study presents a retrospective examination of
      toxicological analysis results from whole blood in cases which gave a positive
      screening result for benzodiazepines in oral fluid using the DrugWipe Single
      device (Securetec). Use of oral fluid on-site screening tests and blood
      confirmation analyses reflects the real situation in many countries. The data
      were compiled from the databases of Alcohol and Drug Analytics Unit at the
      National Institute for Health and Welfare. Confirmation analysis results in whole
      blood were obtained using gas chromatography-mass spectrometry. Data were from
      224 real cases in which the Finnish police had conducted a DrugWipe Single
      benzodiazepines test on drivers suspected of driving under the influence of drugs
      (DUID). The benzodiazepine concentrations encountered in positive oral fluid
      screening cases in this study indicate that the device is able to detect these
      substances even at relatively low levels. However, the DrugWipe device does not
      enable any distinction between therapeutic use and harmful use of benzodiazepines
      at higher doses.

PMID- 21740692
TI  - Urine drug testing of chronic pain patients. IV. prevalence of gabapentin and
      pregabalin.
AB  - Gabapentin and pregabalin are well established for the treatment of seizures and
      neuropathic pain. Both drugs are eliminated primarily unchanged by renal
      excretion. As part of an ongoing research program to improve and expand drug
      testing methods for compliance monitoring of pain patients, the prevalence and
      concentrations of gabapentin and pregabalin in urine specimens from chronic pain
      patients were determined by a validated liquid chromatography-tandem mass
      spectrometry assay. The study was approved by an Institutional Review Board. A
      total of 57,542 urine specimens from 231 pain clinics located in 19 states were
      analyzed over the period of November 24, 2009, through May 2010. The limit of
      quantitation (LOQ) and upper LOQ of the assays for both drugs were 2.5 and 1000
      MUg/mL, respectively. Gabapentin was identified in 7013 specimens (12.2%
      prevalence), and pregabalin was identified in 4799 patients (8.3% prevalence).
      Generally, gabapentin concentrations were more than twofold higher than
      pregabalin, consistent with their relative potencies. Interestingly, both drugs
      were found in specimens from 249 patients, likely representing switching of
      prescriptions by the prescriber.

PMID- 21740693
TI  - Analytical data for identification of the Cannabimimetic Phenylacetylindole JWH
      203.
AB  - We identified the synthetic cannabinoid JWH-203 [1-pentyl-3-(2'
      chlorophenylacetyl) indole] by coordination of various spectroscopic analytical
      procedures; the data that we obtained may be useful for confirming the presence
      of this phenylacetylindole in illegally distributed products. In previous
      studies, several molecules that were identified as synthetic cannabinoids were
      found in different products advertised as herbal mixtures; the identification of
      new psychotropic molecules surreptitiously included in products allows them to be
      added to the official list of psychotropic substances possessing cannabimimetic
      activity. We used liquid chromatography-mass spectrometry and gas chromatography
      mass spectrometry techniques to determine basic information about the structure
      of JWH-203; our data were corroborated by the results of liquid chromatography
      ultraviolet spectroscopy and confirmed by nuclear magnetic resonance analysis and
      high-resolution accurate mass detection.

PMID- 21740694
TI  - The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive
      urine amphetamine immunoassay results.
AB  - Amphetamines and methamphetamines are part of an important class of drugs
      included in most urine drugs of abuse screening panels, and a common assay to
      detect these drugs is the Amphetamines II immunoassay (Roche Diagnostics). To
      demonstrate that meta-chlorophenylpiperazine (m-CPP), a trazodone metabolite,
      cross-reacts in the Amphetamines II assay, we tested reference standards of m-CPP
      at various concentrations (200 to 20,000 g/L). We also tested real patient urine
      samples containing m-CPP (detected and quantified by HPLC) with no detectable
      amphetamine, methamphetamine, or MDMA (demonstrated by GC MS). In both the m-CPP
      standards and the patient urine samples, we found a strong association between m
      CPP concentration and Amphetamines II immunoreactivity (r = 0.990 for the urine
      samples). Further, we found that patients taking trazodone can produce urine with
      sufficient m-CPP to result in false-positive Amphetamines II results. At our
      institution, false-positive amphetamine results occur not infrequently in
      patients taking trazodone with at least 8 trazodone-associated false-positive
      results during a single 26-day period. Laboratories should remain cognizant of
      this interference when interpreting results of this assay.

PMID- 21740695
TI  - Selection of an immunoassay screening cutoff concentration for opioids in oral
      fluid.
AB  - A retrospective analysis of data from oral fluid specimens was conducted in order
      to identify a relevant cutoff concentration for opiates and/or synthetic opiates
      in oral fluid. Previously proposed regulations from the Substance Abuse and
      Mental Health Services Administration (SAMHSA) have recommended 40 MUg/L as a
      cutoff concentration. In this study, data from oral fluid specimens collected
      using the QuantisalTM device and screened with enzyme linked immunosorbent assays
      (ELISA) for both opiates and oxycodone were retrospectively assessed for screen
      positives > 20 MUg/L and those between negative and 20 MUg/L. Specimens
      identified at these concentrations were then analyzed using liquid chromatography
      with tandem mass spectral detection using a fully validated procedure. Overall,
      156 positive specimens were identified using 40 MUg/L; 191 specimens using 20
      MUg/L; and 241 specimens between negative and 20 MUg/L. Specifically, the number
      of 6-acetylmorphine (6-AM) positives increased from 10 to 16; morphine 4 to 9;
      codeine from 11 to 19; oxycodone from 56 to 74; hydrocodone from 73 to 119; and
      hydromorphone from 2 to 4 when specimens with enzyme inhibition between negative
      and 20 MUg/L were analyzed. For workplace testing where only codeine, morphine,
      and 6-AM are considered, the use of a lowered cutoff concentration produced
      significant increases in the positive rate.

PMID- 21740696
TI  - Suicide with cisatracurium and thiopental: forensic and analytical aspects.
AB  - The suicide of a 43-year-old male by intravenous injection of cisatracurium, a
      non-depolarizing neuromuscular blocking agent, and thiopental, an ultra-short
      acting barbiturate, is presented. Systematic toxicological screening by gas
      chromatography-mass spectrometry (GC-MS), liquid chromatography (LC)-diode-array
      detection, and LC-MS-MS confirmed the presence of thiopental. A large peak in the
      GC-MS chromatogram was matched by the Pfleger-Maurer library as corlumine, but
      neither atracurium neither its metabolite, laudanosine, were detected. To confirm
      the absence or the presence of laudanosine in the blood sample, an ultra
      performance liquid chromatography-MS-MS method for cisatracurium and laudanosine
      quantification was developed. The calibration range was 2.5-500 ng/mL for
      laudanosine and 10-500 ng/mL for cisatracurium. The biases were lower than 12.3%.
      Intraday and interday precisions, expressed as coefficient of variation, were
      lower than 13.3%. This method allowed to confirm the presence of laudanosine and
      measurement of laudanosine in all samples. The femoral blood concentration was
      therapeutic (0.46 MUg/mL). This case report documents a possible analytical
      pitfall and describes a simple and fast method for cisatracurium determination.
      Moreover, the purpose of this case report was to document the postmortem
      redistribution of cisatracurium and laudanosine, which could help make it
      possible to interpret tissue or cardiac blood concentrations in forensic cases
      where femoral blood is not available.

PMID- 21740697
TI  - A better understanding of the interpretation of postmortem blood drug
      concentrations.

PMID- 21740698
TI  - The adult dental health survey 2009.

PMID- 21740699
TI  - Oral disease prevention for older people.
AB  - This opinion paper reviews trends in oral disease and its management in older
      people, in response to a challenge, in an editorial in The Lancet, to the
      traditional curative model of dentistry and the publication of the most recent
      Adult Dental Health Survey. It highlights the challenge of an ageing population
      and its oral health needs and management. Professional issues in relation to
      preventive care are discussed with emphasis on the importance of identifying
      patient risk and providing preventive care, together with improving the uptake of
      dental care among older people.

PMID- 21740700
TI  - An investigation into the bitewing radiographic prescribing patterns of West Kent
      general dental practitioners.
AB  - AIMS: The primary aims of the study were to investigate the use of bitewing
      radiography within primary dental care and adherence to guidelines on bitewing
      radiography by general dental practitioners (GDPs) in the West Kent Primary Care
      Trust (PCT) area. Within the overall aims, the study had objectives to
      investigate the use of radiographic guidelines, audit and caries risk assessment,
      the influence of private and National Health Service (NHS) practice, and the
      influence of the demographic profile of the GDPs on these variables. METHODS:
      Data were gathered via a piloted self-completion questionnaire, circulated to all
      GDPs listed on the NHS Choices website as practising in the West Kent PCT area.
      Three mailings and follow-up telephone calls were used. The resulting data were
      entered into a statistical software database and, where relevant, statistically
      tested, using the chi-square test. RESULTS: Of 223 GDPs, 167 responded (75%).
      GDPs with a high NHS commitment were significantly less likely to follow Faculty
      of General Dental Practice (UK) guidance on prescribing bitewing radiographs for
      adults (P<0.01) and children (P<0.05) than were mainly private GDPs. Mainly NHS
      GDPs were more likely 'always/mostly' to follow National Institute for Health and
      Clinical Excellence guidance (83 compared to 59) (P<0.05) and also to risk-assess
      patients (83 compared to 62). Only 115 (71%) had carried out a radio graphic
      audit or peer review in the preceding three years. Those with postgraduate
      qualifications were more likely (P<0.05) to carry out radiographic audit.
      CONCLUSIONS: The study confirmed previous research reporting the under-use of
      radiography for caries detection and also the failure of some GDPs to comply with
      ionising radiation regulations. West Kent GDPs with a high NHS commitment were
      less likely to follow radiographic guidance than their private counterparts. This
      suggests that further efforts to disseminate information on radiographic
      guidelines and to educate GDPs are necessary to improve adherence with all
      aspects of radiography within general dental practice. Research into factors that
      influence GDPs' decision-making with regards to radiographic prescription may
      further inform the profession as to the best methods to lead to behavioural
      change. The dental profession and its regulators need to make a concerted effort
      to educate and inform GDPs so that this behaviour is modified.

PMID- 21740701
TI  - Desmoplastic fibroma of the mandible: case report and review of literature.
AB  - Desmoplastic fibroma is a rare benign and locally aggressive myo fibroblastic
      tumour, frequently seen in the second or third decades of life. The mandible and
      the maxilla are infrequently involved, and the mandible is the most commonly
      affected of the facial bones. Nevertheless, reports of desmoplastic fibroma
      affecting the mandible are scarce in the literature. This article reports a rare
      case of desmoplastic fibroma affecting the angle of the mandible in a 10-year-old
      Indian male. In addition, a review of literature relating to desmoplastic fibroma
      affecting the angle of the mandible is presented.

PMID- 21740702
TI  - Making the grade? Modification of dental radiograph quality ratings.
AB  - AIMS: To compare the intra- and inter-assessor agreement and operator preference
      of a modified (four-grade) quality rating system for dental radiographs with the
      current National Radiological Protection Board (NRPB) (three-grade) quality
      rating system. METHODS: Sixty radiographic images of varying quality were
      selected by retrospective review of dental records from a general dental
      practice. The images were sorted into groups to represent examples of
      radiographic quality (1=excellent, 2=diagnostically acceptable, 3=diagnostically
      compromised, 4=unacceptable). A 'gold standard' for radiological quality
      assessment was provided by a consultant in dental and maxillofacial radiology. A
      compact disc (CD) of the 60 images was produced and posted to a panel of 14
      general dental practitioners (GDPs) who were asked to grade the quality of the
      images using two different systems on two occasions separated by a washout period
      of two days. The practitioners graded the radiographs using the currently
      accepted method for assessing radiographic quality (the three-grade NRPB system)
      and the alternative four-grade system. The quality of the images on the CD was
      deemed appropriate by the consultant. RESULTS: The strength of inter-assessor
      agreement was weaker when using a four-grade system in comparison to a three
      grade system, reducing to a mean of k=0.51 from a mean of k=0.61 when using the
      original grading system. Mean agreement did not fall below 'moderate agreement'
      (k=0.41-0.60). Eleven of the 14 GDPs preferred the four-grade system. CONCLUSION:
      The GDPs who participated in this study preferred the four-grade system to the
      three-grade system when comparing the quality of dental radiographs. However, the
      strength of agreement was weaker when using the four-grade system in comparison
      to the three-grade system. Overall, the results are equivocal. However, they
      should help to inform specialist dental radiology panels, should revision of
      quality grading be undertaken in the future.

PMID- 21740703
TI  - An introduction to research for primary dental care clinicians part 4: stage 6a.
      Obtaining ethical approval.

PMID- 21740704
TI  - An introduction to research for primary dental care clinicians part 5: stage 6b.
      Obtaining funding.

PMID- 21740705
TI  - Evaluation of Escherichia coli O157:H7 translocation and decontamination for beef
      vacuum-packaged subprimals destined for nonintact use.
AB  - The translocation of Escherichia coli O157:H7 as well as the impact of water
      washing and partial or complete surface trimming as possible pathogen reduction
      strategies were evaluated for vacuum-packaged beef subprimals destined for
      nonintact use. Cap-on and cap-off beef top sirloin butts were inoculated with two
      levels of E. coli O157:H7: a high-inoculum level of approximately 10(4) CFU/cm(2)
      and a low-inoculum level of approximately 10(2) CFU/cm(2). Following inoculation,
      the subprimals were vacuum packaged and stored for 0, 14, or 28 days. Upon
      removal from storage, the following sites were evaluated: exterior of the bag,
      purge, the inoculation site on the subprimal, the area adjacent to the
      inoculation site, and the surface opposite from the inoculation site. The
      following treatments then were applied: water wash, water wash followed by full
      surface trimming, water wash followed by partial-surface trimming, full-surface
      trimming, full-surface trimming followed by water wash, partial-surface trimming,
      and partial-surface trimming followed by water wash. For both high- and low
      inoculated top sirloin butts, contamination of adjacent and opposite surfaces was
      found after vacuum packaging. Of the treatments applied, water washing alone was
      the least effective for both high- and low-inoculated subprimals. Full trimming,
      with or without a water wash, proved to be the most effective treatment used to
      reduce E. coli O157:H7 to nondetectable levels.

PMID- 21740706
TI  - Inactivation of Shiga toxin-producing O157:H7 and non-O157:H7 Shiga toxin
      producing Escherichia coli in brine-injected, gas-grilled steaks.
AB  - We quantified translocation of Escherichia coli O157:H7 (ECOH) and non-O157:H7
      verocytotoxigenic E. coli (STEC) into beef subprimals after brine injection and
      subsequently monitored their viability after cooking steaks cut therefrom. Beef
      subprimals were inoculated on the lean side with ca. 6.0 log CFU/g of a five
      strain cocktail of rifampin-resistant ECOH or kanamycin-resistant STEC, and then
      passed once through an automatic brine-injector tenderizer, with the lean side
      facing upward. Brine solutions (9.9% +/- 0.3% over fresh weight) consisted of
      3.3% (wt/vol) of sodium tripolyphosphate and 3.3% (wt/vol) of sodium chloride,
      prepared both with (Lac(+), pH = 6.76) and without (Lac(-), pH = 8.02) a 25%
      (vol/vol) solution of a 60% potassium lactate-sodium diacetate syrup. For all
      samples injected with Lac(-) or Lac(+) brine, levels of ECOH or STEC recovered
      from the topmost 1 cm (i.e., segment 1) of a core sample obtained from tenderized
      subprimals ranged from ca. 4.7 to 6.3 log CFU/g; however, it was possible to
      recover ECOH or STEC from all six segments of all cores tested. Next, brine
      injected steaks from tenderized subprimals were cooked on a commercial open-flame
      gas grill to internal endpoint temperatures of either 37.8  degrees C (100 
      degrees F), 48.8  degrees C (120  degrees F), 60  degrees C (140  degrees F), or
      71.1  degrees C (160  degrees F). Regardless of brine formulation or temperature,
      cooking achieved reductions (expressed as log CFU per gram) of 0.3 to 4.1 of ECOH
      and 0.5 to 3.6 of STEC. However, fortuitous survivors were recovered even at 71.1
      degrees C (160  degrees F) for ECOH and for STEC. Thus, ECOH and STEC behaved
      similarly, relative to translocation and thermal destruction: Tenderization via
      brine injection transferred both pathogens throughout subprimals and cooking
      highly contaminated, brine-injected steaks on a commercial gas grill at 71.1 
      degrees C (160  degrees F) did not kill all cells due, primarily, to nonuniform
      heating (i.e., cold spots) within the meat.

PMID- 21740707
TI  - Effect of antimicrobial coatings on the radiosensitization of Escherichia coli,
      Salmonella typhimurium, and Listeria monocytogenes in fresh broccoli.
AB  - Radiosensitization of Listeria monocytogenes, Escherichia coli, Salmonella
      Typhimurium, and aerobic microflora was evaluated in broccoli florets coated by
      antimicrobial coatings and treated with different doses of gamma-radiation.
      Broccoli florets were inoculated with aerobic microflora isolated from broccoli
      and with pathogenic bacteria (L. monocytogenes, E. coli, and Salmonella
      Typhimurium) at 10(6) CFU/ml. Inoculated florets were then coated with
      methylcellulose-based coating containing various mixtures of antimicrobial
      agents: organic acids plus lactic acid bacteria (LAB metabolites), organic acids
      plus citrus extract, organic acids plus citrus extract plus spice mixture, and
      organic acids plus rosemary extract. Coated florets were irradiated with various
      doses (0 to 3.3 kGy), and microbial analyses were conducted to calculate the
      D(10)-value and relative sensitivity. All antimicrobial coatings had almost the
      same effect of increasing the radiosensitivity of L. monocytogenes (from 1.31 to
      1.45 times) to gamma-irradiation. The coating containing organic acid plus citrus
      extract was the most efficient formulation for increasing the radiosensitization
      of E. coli and aerobic microflora, by 2.40 and 1.76 times, respectively, compared
      with the control without the antimicrobial coating. The coating containing
      organic acids plus LAB metabolites was the most effective formulation for
      increasing the radiosensitization (by 2.4 times) of Salmonella Typhimurium.
      Results suggest that the spice extract, when mixed with organic acids and citrus
      extract, might protect E. coli and aerobic microflora from the effects of gamma
      irradiation.

PMID- 21740708
TI  - Salmonellosis in finishing pigs in Spain: prevalence, antimicrobial agent
      susceptibilities, and risk factor analysis.
AB  - A herd-based survey of Salmonella in pigs was carried in a major pig producing
      region of Spain. Mesenteric lymph nodes were collected from the carcasses of 25
      pigs from each of 80 herds at time of slaughter. Salmonella spp. were isolated
      from 31% of animals and 94% of herds. Within-herd prevalence ranged from 4 to
      88%, with the prevalence in most herds being greater than 10%. A large diversity
      of Salmonella serotypes was found, with Typhimurium, 4,[5],12:i:-, and Rissen
      being the most prevalent. Two or more serotypes coexisted in 73% of the herds.
      Salmonella Typhimurium was present in 68% of the herds. Most (82%) of the
      Salmonella isolates belonged to serogroups targeted by enzyme-linked
      immunosorbent assay tests for pig salmonellosis. Resistance to at least one
      antimicrobial agent was detected in 73% of the strains, and one or more resistant
      strains were recovered from pigs in 93% of the herds. Antimicrobial agent
      resistance (AR) was more frequent among the most prevalent than it was among the
      rarer serotypes. Twenty-five multi-AR patterns were found. Resistance to three or
      more families of antimicrobial agents was found in 75% of AR strains. The finding
      that many of the herds yielded isolates of several multi-AR patterns indicates
      that Salmonella infections were acquired from multiple sources. High prevalence
      of Salmonella in herds was associated with lack of rodent control programs, herds
      from farms with only finishing pigs, herds managed by more than one full-time
      worker, herds for which the source of drinking water was not a city supply, and
      relatively long fattening times.

PMID- 21740709
TI  - Efficacy of home-style dehydrators for reducing Salmonella on whole-muscle
      chicken.
AB  - Home-style dehydrators commonly used by consumers have limited relative humidity
      (RH) and temperature control. To evaluate the effect of dehydrator load on
      temperature and RH and subsequent reduction of Salmonella on whole-muscle
      chicken, chicken breasts were rolled and cut into samples (1 to 2 mm thick, 6 by
      6 cm(2)) and inoculated with a five-strain Salmonella cocktail. The samples were
      allowed to air dry for 15 min and then were loaded into home-style three-tray
      (3T) or five-tray (5T) dehydrators, with 12 chicken pieces per tray. No
      difference (P > 0.05) was observed in RH or temperature between the 3T and 5T
      dehydrators. Peak RH was 38% and gradually deceased to 8.5% after 6 h of drying.
      Temperatures peaked at 57  degrees C after 6 h of drying. Dehydrator load had no
      effect (P > 0.05) on lethality for Salmonella. A reduction of 3.3 +/- 0.2 log
      CFU/cm(2) was observed after 6 h of drying. However, sample location affected
      Salmonella reduction (P < 0.05). Samples from the bottom tray had a 1.5-log
      reduction, whereas samples from the top and middle trays had 4.1- and 3.9-log
      reductions, respectively. The water activity of samples after 6 h of drying was
      0.71 +/- 0.17 regardless of tray location or dehydrator type. When chicken was
      dried in home-style dehydrators, increasing the dehydrator load did not increase
      RH or achieve greater Salmonella lethality. Tray location had a significant
      impact on Salmonella lethality. Adequate reduction of Salmonella on chicken was
      not achieved when chamber temperatures were below 57  degrees C with limited RH
      throughout drying.

PMID- 21740710
TI  - Prevalence, distribution, and diversity of Listeria monocytogenes in retail
      environments, focusing on small establishments and establishments with a history
      of failed inspections.
AB  - Despite growing concerns about cross-contamination of ready-to-eat foods with
      Listeria monocytogenes, our knowledge about the ecology and transmission of L.
      monocytogenes in retail establishments has remained limited. We conducted a cross
      sectional study to characterize the prevalence, distribution, and subtype
      diversity of L. monocytogenes in 120 New York State retail deli establishments
      that were hypothesized to present an increased risk for environmental L.
      monocytogenes contamination (i.e., small establishments and establishments with a
      history of failed New York State Agriculture and Markets inspections). Analysis
      of these data along with previously reported data for 121 predominantly larger
      retail establishments in New York State identified establishment size, geographic
      location, and inspection history as significant predictors of L. monocytogenes
      presence and prevalence. The odds of an establishment being L. monocytogenes
      positive were approximately twice as high for large establishments,
      establishments located in New York City, or establishments with poor inspection
      history (as compared with establishments without these attributes), even though
      correlation between location and inspection history complicated interpretation of
      results. Within an establishment, L. monocytogenes was significantly more
      prevalent on nonfood contact surfaces than on food contact surfaces; prevalence
      was particularly high for floors and in floor drains, sinks, the dairy case, and
      milk crates. L. monocytogenes subtype diversity differed between sites, with
      lineage I isolates significantly associated with nonfood contact surfaces and
      lineage II isolates significantly associated with food contact surfaces. Isolates
      belonging to the same ribotype were often found dispersed across multiple sites
      within an operation.

PMID- 21740711
TI  - Listeria monocytogenes contamination in French breeding and fattening turkey
      flocks.
AB  - This study aimed to collect data and create a database related to Listeria
      monocytogenes contamination in breeding and fattening turkey flocks. Seventy-five
      breeding turkey flocks and 86 fattening turkey flocks were sampled. Three hundred
      seventy-five and 428 samples were analyzed in breeding and fattening turkey
      flocks, respectively. L. monocytogenes was detected in 9 of 75 breeding flocks,
      leading to an estimated prevalence of 12% (95% confidence interval, 4.6-19.4). In
      fattening turkeys, the prevalence of L. monocytogenes-positive flocks was 9.3%
      (95% confidence interval, 3.1-15.5). The serotyping of L. monocytogenes strains
      highlighted the dominance of serovar 1/2a in breeding as well as in fattening
      turkeys. The relationship between rearing practices and L. monocytogenes status
      in turkey flocks was studied by using multiple correspondence analyses and then a
      hierarchical classification. Results were separated into two classes and revealed
      profiles that were associated with the presence or the absence of L.
      monocytogenes. This study highlighted the need to implement strict sanitary
      measures to reduce the risk of L. monocytogenes contamination in turkey
      production.

PMID- 21740712
TI  - Transcriptome analysis of Listeria monocytogenes grown on a ready-to-eat meat
      matrix.
AB  - The contamination of ready-to-eat (RTE) meat products with Listeria monocytogenes
      is a major concern for the food industry. For a better understanding of the
      adaptation and survival ability of L. monocytogenes grown on turkey deli meat,
      the transcriptome of L. monocytogenes strain F2365 was determined with a
      microarray. Microarray data were validated with a quantitative real-time reverse
      transcription PCR assay. Based on the microarray data, 39 and 45 genes from L.
      monocytogenes were transcriptionally upregulated and down-regulated,
      respectively. The genes regulated at the transcriptional level were mainly
      involved in energy metabolism, fatty acid and phospholipid metabolism,
      biosynthesis of proteins, transport and binding proteins, DNA metabolism,
      cellular processes, and regulatory functions. No significant change was noted for
      the expression of genes encoding known virulence factors such as sigB, prfA,
      inlA, inlB, plcA, plcB, and hly. These results suggest that L. monocytogenes
      grown on RTE deli meat changes its transcription of proteins involved in its
      metabolic pathways to obtain an energy source or to adapt to environmental change
      without increasing the expression of virulence factors. The global transcriptome
      profiles provide a better understanding of the growth or adaptation of L.
      monocytogenes in RTE meat products.

PMID- 21740713
TI  - Comparison between the resistance of benzalkonium chloride-adapted and 
      nonadapted biofilms of Listeria monocyogenes to modified atmosphere packaging and
      nisin once transferred to mussels.
AB  - Benzalkonium chloride-adapted and -nonadapted Listeria monocytogenes biofilm
      cells were transferred by contact to cooked or live mussels and packed in rich
      CO(2) and O(2), respectively. The viabilities of transferred cells during storage
      of these packed samples at 2.5  degrees C were compared. In addition, in cooked
      mussels the combined effect of CO(2) and nisin against the survival of L.
      monocytogenes was also studied by using a first-order factorial design. The
      results obtained demonstrated that biofilms formed by benzalkonium chloride
      adapted L. monocytogenes cells could be more resistant to the application of
      modified atmospheres rich in CO(2) and nisin once they have been transferred to
      cooked mussels by contact (simulating cross-contamination). This implies an
      increase in the risk associated with the presence of these cells in food
      processing plants. Significant empirical equations obtained after 7, 11, and 20
      days showed an inhibitory effect of CO(2) and nisin against L. monocytogenes.
      However, a significant positive interaction between both variables highlights an
      incompatibility between CO(2) and nisin at high concentrations. Results also
      demonstrated that L. monocytogenes could persist after cross-contamination during
      the processing of live mussels, so L. monocytogenes is of concern as a
      contaminant in live mussels packaged in high-O(2) atmospheres.

PMID- 21740714
TI  - Effect of antimicrobial spice and herb extract combinations on Listeria
      monocytogenes, Staphylococcus aureus, and spoilage microflora growth on cooked
      ready-to-eat vacuum-packaged shrimp.
AB  - Two spice and herb extract combinations from galangal (Alpinia galanga), rosemary
      (Rosmarinus officinalis), and lemon iron bark (Eucalyptus staigerana) were
      evaluated for their ability to inhibit the growth of inoculated Listeria
      monocytogenes and Staphylococcus aureus and naturally present spoilage microflora
      on cooked ready-to-eat shrimp stored for 16 days at 4 or 8  degrees C. A
      combination of galangal, rosemary, and lemon iron bark significantly reduced (P <
      0.05) levels of aerobic bacteria and lactic acid bacteria at 4  degrees C on day
      12 by 1.6 and 1.59 log CFU/g, respectively. By day 16, levels of these bacteria
      were equivalent to those of controls. The shrimp treated with this spice and herb
      extract combination had significantly lower (P < 0.05) lipid oxidation from day 4
      to day 16. Similarly, a combination of galangal and rosemary extract
      significantly reduced (P < 0.05) levels of aerobic bacteria and lactic acid
      bacteria at 8  degrees C on day 8 by 2.82 and 2.61 log CFU/g, respectively. By
      days 12 and 16, levels of these bacteria were equivalent to those of controls.
      The shrimp treated with this spice and herb combination had significantly lower
      (P < 0.05) lipid oxidation on days 4 and 16. None of the spice and herb extract
      combinations had an effect on levels of L. monocytogenes or S. aureus or changed
      the color or pH of the shrimp during storage. The results of this study indicate
      that combinations of galangal, rosemary, and lemon iron bark extracts can be used
      to control the growth of spoilage microflora on ready-to-eat shrimp.

PMID- 21740715
TI  - Modeling the occurrence of Mycobacterium avium subsp. paratuberculosis in bulk
      raw milk and the impact of management options for exposure mitigation.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) is the causal agent of
      paratuberculosis (Johne's disease) in cattle and other farm ruminants. The
      potential role of MAP in Crohn's disease in humans and the contribution of dairy
      products to human exposure to MAP continue to be the subject of scientific
      debate. The occurrence of MAP in bulk raw milk from dairy herds was assessed
      using a stochastic modeling approach. Raw milk samples were collected from bulk
      tanks in dairy plants and tested for the presence of MAP. Results from this
      analytical screening were used in a Bayesian network to update the model
      prediction. Of the 83 raw milk samples tested, 4 were positive for MAP by culture
      and PCR. We estimated that the level of MAP in bulk tanks ranged from 0 CFU/ml
      for the 2.5th percentile to 65 CFU/ml for the 97.5th percentile, with 95%
      credibility intervals of [0, 0] and [16, 326], respectively. The model was used
      to evaluate the effect of measures aimed at reducing the occurrence of MAP in raw
      milk. Reducing the prevalence of paratuberculosis has less of an effect on the
      occurrence of MAP in bulk raw milk than does managing clinically infected animals
      through good farming practices.

PMID- 21740716
TI  - Incorporation of nisin in poly (ethylene-co-vinyl acetate) films by melt
      processing: a study on the antimicrobial properties.
AB  - Both industry and academia have shown a growing interest in materials with
      antimicrobial properties suitable for food packaging applications. In this study,
      we prepared and characterized thin films of ethylene-co-vinyl acetate (EVA)
      copolymer with antimicrobial properties. The films were prepared with a film
      blowing process by incorporating a nisin preparation as an antimicrobial agent in
      the melt. Two grades of EVA containing 14 and 28% (wt/wt) vinyl acetate (EVA 14
      and EVA 28, respectively) and two commercial formulations of nisin with different
      nominal activities were used. The effect of the nisin concentration also was
      evaluated. The films with the highest antimicrobial activity were those
      formulated with nisin at the highest activity and EVA with the highest content of
      vinyl acetate. The use of the commercial formulation of nisin with high activity
      in the EVA films allowed reduction in the amount of nisin needed to provide
      antimicrobial properties. Consequently, the mechanical properties of these films
      were only slightly inferior to those of the pure polymers. In contrast, films
      prepared by incorporating more of the nisin with lower activity had poor
      mechanical properties. The effect of different processing temperatures used in
      the preparation of the films on the antimicrobial properties of the films also
      was evaluated. The materials displayed antimicrobial properties even when they
      were prepared at temperatures as high as 160  degrees C, probably because of the
      very short processing time (60 to 90 s) required for preparation.

PMID- 21740717
TI  - Evaluation of alkaline phosphatase detection in dairy products using a modified
      rapid chemiluminescent method and official methods.
AB  - Alkaline phosphatase is a ubiquitous milk enzyme that historically has been used
      to verify adequate pasteurization of milk for public health purposes. Current
      approved methods for detection of alkaline phosphatase in milk include the use of
      enzyme photoactivated substrates to give readings in milliunits per liter. The
      U.S. and European public health limit for alkaline phosphatase in pasteurized
      drinks is 350 mU/liter. A modified chemiluminescent method, fast alkaline
      phosphatase, was compared with the approved fluorometric and chemiluminescent
      alkaline phosphatase methods to determine whether the modified method was
      equivalent to the approved methods and suitable for detecting alkaline
      phosphatase in milk. Alkaline phosphatase concentrations in cow's, goat's, and
      sheep's milk and in flavored drinks and cream were determined by three methods.
      Evaluations in each matrix were conducted with pasteurized samples spiked with
      raw milk to produce alkaline phosphatase concentrations of 2 to 5,000 mU/liter.
      The tests were performed by the method developer and then reproduced at a
      laboratory at the National Center for Food Safety and Technology following the
      criteria for a single laboratory validation. The results indicated that the fast
      alkaline phosphatase method was not significantly different from the approved
      chemiluminescent method, with a limit of detection of 20 to 50 mU/liter in all
      the studied matrices. This modified chemiluminescent method detects alkaline
      phosphatase in the 350 mU/liter range with absolute differences from triplicate
      data that are lower and within the range of the allowed intralaboratory
      repeatability values published for the approved chemiluminescent method.

PMID- 21740718
TI  - Electron-beam inactivation of a norovirus surrogate in fresh produce and model
      systems.
AB  - Norovirus remains the leading cause of foodborne illness, but there is no
      effective intervention to eliminate viral contaminants in fresh produce. Murine
      norovirus 1 (MNV-1) was inoculated in either 100 ml of liquid or 100 g of food.
      The inactivation of MNV-1 by electron-beam (e-beam), or high-energy electrons, at
      varying doses was measured in model systems (phosphate-buffered saline [PBS],
      Dulbecco's modified Eagle's medium [DMEM]) or from fresh foods (shredded cabbage,
      diced strawberries). E-beam was applied at a current of 1.5 mA, with doses of 0,
      2, 4, 6, 8, 10, and 12 kGy. The surviving viral titer was determined by plaque
      assays in RAW 264.7 cells. In PBS and DMEM, e-beam at 0 and 2 kGy provided less
      than a 1-log reduction of virus. At doses of 4, 6, 8, 10, and 12 kGy, viral
      inactivation in PBS ranged from 2.37 to 6.40 log, while in DMEM inactivation
      ranged from 1.40 to 3.59 log. Irradiation of inoculated cabbage showed up to a 1
      log reduction at 4 kGy, and less than a 3-log reduction at 12 kGy. On
      strawberries, less than a 1-log reduction occurred at doses up to 6 kGy, with a
      maximum reduction of 2.21 log at 12 kGy. These results suggest that a food matrix
      might provide increased survival for viruses. In foods, noroviruses are difficult
      to inactivate because of the protective effect of the food matrix, their small
      sizes, and their highly stable viral capsid.

PMID- 21740719
TI  - Thermal inactivation of avian influenza virus and Newcastle disease virus in a
      fat-free egg product.
AB  - High-pathogenicity avian influenza (HPAI) virus, low-pathogenicity avian
      influenza (LPAI) virus, virulent Newcastle disease virus (vNDV) and low-virulent
      Newcastle disease virus (lNDV) can be present on the eggshell surface, and HPAI
      viruses and vNDV can be present in the internal contents of chicken eggs laid by
      infected hens. With the increase in global trade, egg products could present
      potential biosecurity problems and affect international trade in liquid and dried
      egg products. Therefore, the generation of survival curves to determine decimal
      reduction times (D(T)-values) and change in heat resistance of the viruses (z(D)
      value) within fat-free egg product could provide valuable information for
      development of risk reduction strategies. Thermal inactivation studies using
      A/chicken/Pennsylvania/1370/83 (H5N2) HPAI virus resulted in D(55)-, D(56)-,
      D(56.7)-, D(57)-, D(58)-, and D(59)-values of 18.6, 8.5, 3.6, 2.5, 0.4, and 0.4
      min, respectively. The z(D)-value was 4.4  degrees C. LPAI virus A/chicken/New
      York/13142/94 (H7N2) had D(55)-, D(56.7)-, D(57)-, D(58)-, D(59)-, and D(60)
      values of 2.9, 1.4, 0.8, 0.7, 0.7, and 0.5 min, respectively, and a z-value of
      0.4  degrees C. vNDV avian paramyxoviruses of serotype 1 (AMPV
      1)/chicken/California/212676/2002 had D(55)-, D(56)-, D(56.7)-, D(57)-, D(58)-,
      and D(59)-values of 12.4, 9.3, 6.2, 5, 3.7, and 1.7 min, respectively. The z(D)
      value was 4.7  degrees C. lNDV AMPV-1/chicken/United States/B1/1948 had D(55)-,
      D(57)-, D(58)-, D(59)-, D(61)-, and D(63)-values of 5.3, 2.2, 1.1, 0.55, 0.19,
      and 0.17 min, respectively, and a z(D)-value of 1.0  degrees C. Use of these data
      in developing egg pasteurization standards for AI and NDV-infected countries
      should allow safer trade in liquid egg products.

PMID- 21740720
TI  - Occurrence of Fusarium mycotoxins in rice and its milling by-products in Korea.
AB  - A total of 201 samples of brown rice, polished rice, and two types of by
      products, blue-tinged rice and discolored rice, were collected from rice stores
      maintained at 51 rice processing complexes in Korea. These samples were analyzed
      for the presence of Fusarium mycotoxins such as deoxynivalenol (DON), nivalenol
      (NIV), and zearalenone (ZEA). Contaminants (and their ranges) found in discolored
      rice samples were DON (59 to 1,355 ng g(-1)), NIV (66 to 4,180 ng g(-1)), and ZEA
      (25 to 3,305 ng g(-1)); those found in blue-tinged (less-ripe) rice were DON (86
      to 630 ng g(-1)), NIV (50 to 3,607 ng g(-1)), and ZEA (26 to 3,156 ng g(-1)).
      Brown rice samples were contaminated mostly with NIV and ZEA (52 to 569 ng g(-1)
      and 47 to 235 ng g(-1), respectively). Polished rice samples were largely free
      from mycotoxins, although one sample was contaminated with NIV (77 ng g(-1)).
      When the fungal flora associated with each rice sample was investigated, blue
      tinged rice was the most often contaminated with Fusarium graminearum (3.8%),
      followed by the discolored rice (2.4%) and brown rice (1.6%) samples. Using PCR,
      toxin genotyping of 266 isolates of F. graminearum revealed that most isolates
      (96%) were NIV producers. In conclusion, this survey is the first report of the
      cocontamination of Korean rice and its by-products with trichothecenes and ZEA.
      Importantly, it also provides new information on the natural contamination of
      rice by Fusarium mycotoxins.

PMID- 21740721
TI  - Binding of zearalenone, aflatoxin B1, and ochratoxin A by yeast-based products: a
      method for quantification of adsorption performance.
AB  - A methodology was developed to quantify the efficiency of yeast-based products
      for adsorption of three mycotoxins: zearalenone (ZEA), aflatoxin B(1) (AFB(1)),
      and ochratoxin A (OTA). Eight products were tested (yeast cell wall or
      inactivated yeast). The described experimental protocol based on in vitro tests
      provided reliable isotherms for each mycotoxin. The most suitable models were the
      Hill model for ZEA, the Langmuir model for AFB(1), and the Freundlich model for
      OTA. From these models, original mathematical affinity criteria were defined to
      quantify the product adsorption performances for each mycotoxin. The best yeast
      product, a yeast cell wall from baker's yeast, can adsorb up to 68% of ZEA, 29%
      of AFB(1), and 62% of OTA, depending on the mycotoxin concentrations. The
      adsorption capacity largely depended both on yeast composition and mycotoxin, but
      no direct correlation between yeast composition and adsorption capacity was
      found, confirming that adsorption of mycotoxin on yeast-based products involves
      complex phenomena. The results of this study are useful for comparing the
      adsorption efficiency of various yeast products and understanding the mechanisms
      involved in adsorption.

PMID- 21740722
TI  - Escherichia coli O157:H7 genetic diversity in bovine fecal samples.
AB  - Escherichia coli O157:H7 causes foodborne illness in humans; cattle are
      considered a primary reservoir for the organism, and transmission is often
      through contaminated food products or water. The objective of this study was to
      determine the genetic diversity of E. coli O157:H7 within a single individual
      bovine fecal sample based on pulsed-field gel electrophoresis (PFGE) typing.
      Fecal samples (n=601) were collected from dairy and beef cattle at three separate
      facilities, and E. coli O157:H7 was isolated by enrichment, immunomagnetic
      separation, and plating on selective medium. The prevalence of E. coli O157:H7
      was 46 (7.7%) of 601. From each positive fecal sample, up to 10 putative colonies
      were tested, and isolates from samples with at least seven positive colonies were
      subtyped using PFGE and tested for six major virulence genes by multiplex PCR. A
      total of 254 E. coli O157:H7 isolates from 27 samples met these criteria and were
      included in PFGE analysis. Fifteen PFGE subtypes (<100% Dice similarity) were
      detected among the 254 isolates, and there were no common subtypes between the
      three locations. Seven (26%) of 27 fecal samples had E. coli O157:H7 isolates
      with different PFGE subtypes (mean=2.1) within the same sample. The virulence
      gene profiles of different isolates from the same sample were always identical,
      regardless of the number of PFGE types. The results of this study suggest that
      determining the PFGE pattern of a single isolate from a bovine sample may not be
      sufficient when comparing isolates from feces, hides, or carcasses, because
      multiple PFGE subtypes are present.

PMID- 21740723
TI  - Molecular characterization of the probiotic strain Bacillus cereus var. toyoi
      NCIMB 40112 and differentiation from food poisoning strains.
AB  - Bacillus cereus var. toyoi strain NCIMB 40112 (Toyocerin), a probiotic authorized
      in the European Union as feed additive for swine, bovines, poultry, and rabbits,
      was characterized by DNA fingerprinting applying pulsed-field gel electrophoresis
      and multilocus sequence typing and was compared with reference strains (of
      clinical and environmental origins). The probiotic strain was clearly
      characterized by pulsed-field gel electrophoresis using the restriction enzymes
      Apa I and Sma I resulting in unique DNA patterns. The comparison to the clinical
      reference strain B. cereus DSM 4312 was done with the same restriction enzymes,
      and again a clear differentiation of the two strains was possible by the
      resulting DNA patterns. The use of the restriction enzymes Apa I and Sma I is
      recommended for further studies. Furthermore, multilocus sequence typing analysis
      revealed a sequence type (ST 111) that was different from all known STs of B.
      cereus strains from food poisoning incidents. Thus, a strain characterization and
      differentiation from food poisoning strains for the probiotic strain was
      possible.

PMID- 21740724
TI  - Incorporation of probiotic bacteria in whey cheese: decreasing the risk of
      microbial contamination.
AB  - For dairy products that are consumed fresh, contamination by spoilage
      microorganisms and pathogens from the environment is a major concern.
      Contamination has been associated with a number of outbreaks of foodborne
      illnesses; however, consistent data pertaining to the microbial safety of whey
      cheeses specifically have not been reported. Hence, the goals of this research
      effort were (i) to manufacture a probiotic whey cheese with Bifidobacterium
      animalis and Lactobacillus casei and (ii) to assess the antimicrobial activity of
      these probiotics against a set of foodborne pathogens (Listeria innocua,
      Salmonella Enteritidis, and Staphylococcus aureus) and food spoilage
      microorganisms (Pseudomonas aeruginosa and Escherichia coli). Three ranges of
      these microbial contaminants were used for inoculation of cheeses: 10(3) to
      10(4), 10(4) to 10(6), and 10(6) to 10(8) CFU/g. Inoculation in plain culture
      medium served as a control. The inhibition produced by the probiotics was
      calculated, and the major effect was found to be bacteriostatic. In specific
      cases, full inhibition was observed, i.e., by B. animalis against P. aeruginosa
      and by L. casei against Salmonella Enteritidis and L. innocua. Conversely, the
      least inhibition was detected for L. casei against P. aeruginosa. Our results
      suggest that use of these probiotic strains can extend the shelf life of whey
      cheeses and make them safer by delaying or preventing growth of common
      contaminant bacteria.

PMID- 21740725
TI  - Effects of materials containing antimicrobial compounds on food hygiene.
AB  - Surfaces with microorganisms may transfer unwanted microorganisms to food through
      cross-contamination during processing and preparation. A high hygienic status of
      surfaces that come in contact with food is important in order to reduce the risk
      of cross-contamination. During the last decade, products containing antimicrobial
      compounds, such as cutting boards, knives, countertops, kitchen utensils,
      refrigerators, and conveyor belts, have been introduced to the market, claiming
      hygienic effects. Such products are often referred to as "treated articles." Here
      we review various aspects related to treated articles intended for use during
      preparation and processing of food. Regulatory issues and methods to assess
      antibacterial effects are covered. Different concepts for treated articles as
      well as their antibacterial activity are reviewed. The effects of products with
      antimicrobials on food hygiene and safety are discussed.

PMID- 21740726
TI  - Management and long-term outcome of patients with chronic neuromuscular disease
      admitted to the intensive care unit for acute respiratory failure: a single
      center retrospective study.
AB  - BACKGROUND: Patients with chronic neuromuscular disease represent less than 10%
      of those receiving mechanical ventilation in the intensive care unit (ICU).
      Little has been reported regarding either ICU management of acute respiratory
      failure (ARF) in the era of noninvasive mechanical ventilation (NIV) or long-term
      outcomes. OBJECTIVE: To describe the respiratory management of patients with
      chronic neuromuscular diseases admitted to our university hospital ICU for ARF,
      and the long-term outcomes. METHODS: We retrospectively analyzed patients with
      chronic neuromuscular diseases admitted to our ICU for a first episode of ARF
      between January 1, 1996, and February 27, 2007. We assessed severity of illness
      on ICU admission, respiratory management during ICU stay, and outcomes on June
      15, 2008. RESULTS: During the study period, 87 patients (44 with hereditary and
      43 with acquired neuromuscular diseases) had their first ARF episode that
      required ICU admission. In the hereditary-diseases group and the acquired
      diseases group, respectively, the rates of NIV use during the ICU stay were 82%
      and 63% (P = .040), the intubation rates were 30% and 56% (P = .02), and the
      tracheotomy rates were 9% and 12% (difference not significant). At the final
      assessment (median 3 years) the mortality rate was 58%, and mortality was not
      significantly related to the type of neuromuscular disease. At final assessment,
      46% of the patients were on NIV and 29% had tracheotomy. CONCLUSIONS: In our ICU,
      chronic neuromuscular disease is an uncommon cause of ARF, for which we often use
      NIV. These patients had a low probability of death in the ICU. Long-term outcome
      was independent of the type of neuromuscular disease.

PMID- 21740727
TI  - Chester step test in patients with COPD: reliability and correlation with
      pulmonary function test results.
AB  - BACKGROUND: The 5-stage Chester step test assesses aerobic capacity in healthy
      subjects. It has not been tested in patients with COPD. OBJECTIVE: To determine
      the reliability of the Chester step test in patients with COPD and correlation
      with pulmonary function test and exercise test results. METHODS: Thirty-two
      patients (mean +/- SD FEV(1) 46 +/- 15% of predicted) undertook 2 Chester step
      tests and two 6-min walk tests, on different days, in random order. A subgroup of
      11 patients performed incremental cycle ergometry. RESULTS: Thirty-one patients
      performed stage 1 of the Chester step test. Nineteen patients performed stage 2
      of the Chester step test. The number of steps was highly reproducible: 66 +/- 41
      steps vs 68 +/- 41 steps. There was no difference in heart rate or S(pO(2))
      between the 2 Chester step tests at the peak of exercise or at the end of each
      stage. There was a significant correlation between number of steps and FEV(1) (r
      = 0.43, P = .02), and 6-min walk distance (r = 0.60, P = .001). Heart rate
      increased according to advanced stages of the Chester step test, up to 81 +/- 13%
      of predicted. There was a significant correlation between number of steps and
      peak heart rate (r = 0.55, P = .001). In the 11 patients who performed the
      incremental cycling test there was a significant correlation between number of
      steps and peak work load (r = 0.69, P = .02). In the 6 patients in whom oxygen
      uptake could be estimated from the Chester step test, oxygen uptake was higher
      than that measured at the peak of the cycling test (30.8 +/- 5.1 mL/kg/min vs
      17.4 +/- 4.5 mL/kg/min, respectively, P = .001). CONCLUSIONS: Despite being
      highly reproducible, the Chester step test had a very short duration in patients
      with COPD. The number of steps incremented in each stage seems to be too large
      for these patients. An adaptation of the Chester step test should be considered
      for patients with COPD.

PMID- 21740728
TI  - Lung hernia associated with hemothorax following cardiopulmonary resuscitation.
AB  - Lung herniation is a rare event that can occur spontaneously or traumatically.
      Thoracic hernias are usually associated with a chest-wall defect. We report a
      case of thoracic lung hernia that occurred 2 days after traumatic cardiopulmonary
      resuscitation, after the formation of a large hemothorax.

PMID- 21740729
TI  - Success stories: use of patient vignettes to assess the ability of physicians to
      predict extubation success.

PMID- 21740730
TI  - Is volume inferior to pressure?

PMID- 21740731
TI  - Are contraindications to extracorporeal membrane oxygenation slowly vanishing?

PMID- 21740732
TI  - Posture perfect: the role of positioning during bronchodilator administration
      with oxygen or heliox.

PMID- 21740733
TI  - Biochemical recurrence of prostate cancer: the controversial recognition and
      management.

PMID- 21740734
TI  - Modified biological training model for percutaneous renal surgery with ultrasound
      and fluroscopy guidance.
AB  - BACKGROUND: The 12th rib is an important anatomic marker in the process of
      percutaneous renal surgery; while the previous models without ribs can not
      provide close simulation conditions to human upper abdomen. To facilitate the
      learning and training of percutaneous renal access and intrarenal procedures
      under ultrasound and fluoroscopy guidance, we reported a biological bench model
      for percutaneous renal surgery. METHODS: The model was developed using an ex vivo
      porcine kidney with a longer than 3 cm ureter, a flap of full thickness of
      thoracic wall with skin, subcutaneous fascia, muscle and two ribs, as well as the
      standard equipment for percutaneous nephrolithotomy. The porcine kidney with a
      catheterized ureter was placed within the porcine flap and fixed to a wooden
      board with two long steel nails. Afterward, contrast medium or physiological
      saline (0.9% sodium chloride solution) was injected through the ureter, and the
      urinary system was examined with a fluoroscopy unit or an ultrasound. Artificial
      stone material was implanted in the renal pelvis. After practicing, the model
      could be dissected for kidney examination and a technical analysis. RESULTS: The
      advantage of this model was simple to set up and inexpensive, by using widely
      available material. The biological bench model can be employed for percutanous
      renal access, tract dilation, nephroscopy, and stone disintegration in the
      training and learning of clinical practice. Imaging is feasible under
      fluoroscopic and ultrasound guidance. The kidney models were utilized in hands on
      courses with over 100 people, and 90.5% attendants rated the porcine kidney model
      for simulation of percutaneous renal surgery as "very helpful" or "helpful".
      CONCLUSION: This biological training model simulates realistically the clinical
      procedure of percutaneous nephrolithotomy under fluoroscopic and ultrasound
      guidance.

PMID- 21740735
TI  - Renal function of donors and recipients after living donor kidney transplantation
      in a Chinese cohort.
AB  - BACKGROUND: Living donor kidney transplantation (LKT) has been booming in China.
      This study aimed to elucidate the renal function of both Chinese donors and
      recipients after the donation and transplantation. METHODS: One hundred and forty
      one pairs of donors and recipients for LKT were randomly selected and followed up
      for up to seven years. The donors' and recipients' renal function was recorded
      before and after operation. RESULTS: The donors presented a mean age of (43.9 +/-
      7.5) years at donation. The female contributed 101/141 (71.6%) in all donors, and
      no effect was shown between genders on healthy donors' renal function. The
      donors' glomerular filtration rates (GFR) were (119.5 +/- 20.4) ml/min, (85.2 +/-
      17.6) ml/min, (87.2 +/- 15.9) ml/min, (82.1 +/- 14.6) ml/min and (83.0 +/- 13.7)
      ml/min preoperatively, and for five days, three months, one year and beyond one
      year after the operation. The donors for the period of 1 - 3 years, 3 - 5 years
      and more than 5 years after donation showed GFR as (83.9 +/- 12.7) ml/min, (83.0
      +/- 17.6) ml/min, and (80.9 +/- 20.8) ml/min, respectively, no statistically
      significant difference was found. Moreover, no significant clinical changes in
      blood pressure and proteinuria were found among the donors. In the recipients,
      delayed graft function (DGF) rate was 6.4%, acute rejection rate was 11.3%, and
      GFR were (66.5 +/- 16.4) ml/min, (73.2 +/- 19.6) ml/min and (63.9 +/- 18.6)
      ml/min respectively at three months, one year and beyond one year post
      transplantation respectively. CONCLUSION: The donors/recipients of LKT in Chinese
      population experience well-functioning remaining/donor kidneys.

PMID- 21740736
TI  - Efficacy and postoperative complication of tension-free vaginal tape-Secur for
      female stress urinary incontinence.
AB  - BACKGROUND: As the third-generation tension-free tape for female stress urinary
      incontinence (SUI), tension-free vaginal tape (TVT)-Secur has decreased the
      common complications associated with TVT and tension-free vaginal tape
      transobturator (TVT-O), such as bladder perforation and obstruction of the
      bladder outlet; but its efficacy and persistence were still controversial. The
      aim of this study was to prospectively evaluate and compare the postoperative
      efficacy and complication at different follow-up time. METHODS: Patients with
      SUI, who underwent TVT-Secur treatment in two hospitals from October 2008 to
      October 2009, were selected. By analyzing preoperative and intraoperative data
      and postoperative complications, the therapeutic effect and satisfaction at
      different follow-up stages were evaluated. RESULTS: A total of 30 female patients
      participated in this study. Patients were scheduled for follow-up at the 1st
      month, 3rd month, 6th month and 12th month, while the cure rate was 83.3% (25
      patients), 66.7% (20 patients), 63.3% (19 patients) and 60.0% (18 patients)
      respectively and the overactive bladder (OAB) symptoms appeared in 11 patients
      (36.7%), 10 patients (33.3%), 6 patients (20%) and 7 patients (23.3%)
      respectively. CONCLUSION: With the follow-up time becoming longer, TVT-Secur has
      a high recurrence rate of SUI, the therapeutic effect from the 3rd month to the
      12th month is relatively persistent.

PMID- 21740737
TI  - Risk factors for postoperative seromas in Chinese breast cancer patients.
AB  - BACKGROUND: Seroma formation is one of the most common complications after breast
      cancer surgery. Various risk factors have been evaluated for their associations
      with the development of seromas in Western populations. However, similar data are
      not available in Chinese series. Therefore, we sought to investigate the
      potential risk factors for Chinese breast cancer patients. METHODS: A prospective
      study of female breast cancer patients undergoing surgery was carried out in
      Cancer Hospital of Fudan University, Shanghai, China. Univariate analyses were
      performed by chi-square test or Student's t test or Mann-Whitney test and
      multivariate analyses by stepwise Logistic regression. The logistic model
      included age (years), total serum protein concentration (g/L), drainage volume on
      postoperative day 3 (POD 3; ml) and time to daily drainage volume not more than
      30 ml (TTV30; days). RESULTS: A total of 158 patients with breast cancer were
      studied. The mean age at diagnosis was (52.14 +/- 10.77) years (range 25 - 92).
      During the follow-up period, 24 (15.2%) patients developed seromas. Calculated as
      continuous variables in the stepwise Logistic regression, age (OR = 1.090, 95%CI
      1.028 - 1.155, P = 0.004), total serum protein concentration (OR = 0.886, 95%CI
      0.791 - 0.992, P = 0.036), drainage volume on POD3 (OR = 1.013, 95%CI 1.002 -
      1.023, P = 0.017) and TTV30 (OR = 1.273, 95%CI 1.039 - 1.561, P = 0.020) were
      independent risk factors for seroma formation. Additionally, significant
      difference in daily drainage volume was substantiated in the analysis by seroma
      formation (P = 0.034) rather than by type of surgery (P = 0.713). CONCLUSIONS:
      Although the pathogenesis of seroma remains controversial, such risk factors as
      age, nutritional status, drainage volume on POD3 and TTV30 should be considered
      for prediction and prevention of seroma formation in Chinese breast cancer
      patients.

PMID- 21740738
TI  - Feasibility and acute toxicity of 3-dimensional conformal external-beam
      accelerated partial-breast irradiation for early-stage breast cancer after breast
      conserving surgery in Chinese female patients.
AB  - BACKGROUND: A growing number of studies worldwide have advocated the replacement
      of whole-breast irradiation with accelerated partial breast irradiation using
      three-dimensional conformal external-beam radiation (APBI-3DCRT) for early-stage
      breast cancer. But APBI can be only used in selected population of patients with
      early-staged breast cancer. It is not replacing the whole breast radiotherapy.
      This study aimed to examine the feasibility and acute normal tissue toxicity of
      the APBI-3DCRT technique in Chinese female patients who generally have smaller
      breasts compared to their Western counterparts. METHODS: From May 2006 to
      December 2009, a total of 48 Chinese female patients (with early-stage breast
      cancer who met the inclusion criteria) received APBI-3DCRT after breast
      conserving surgery at Sun Yat-sen University Cancer Center. The total dosage from
      APBI-3DCRT was 34 Gy, delivered in 3.4 Gy per fractions, twice per day at
      intervals of at least six hours. The radiation dose, volume of the target area
      and volume of irradiated normal tissues were calculated. Acute toxicity was
      evaluated according to the Common Toxicity Criteria (CTC) 3.0. RESULTS: Among the
      48 patients, the planning target volume for evaluation (PTVE) was (90.42 +/-
      9.26) cm3, the ipsilateral breast volume (IBV) was (421.74 +/- 28.53) cm3, and
      the ratio between the two was (20.74 +/- 5.86)%. Evaluation of the dosimetric
      characteristics of the PTVE revealed excellent dosimetric results in 14 patients
      and acceptable results in 34 patients. The dose delivered to the PTVE ranged from
      93% to 110% of the prescribed dose. The average ratio of the volume of PTVE
      receiving 95% of the prescription dose (V95) was (99.26 +/- 0.37)%. The
      habituation index (HI) and the conformity index (CI) were 1.08 +/- 0.01 and 0.72
      +/- 0.02, respectively, suggesting good homogeneity and conformity of the dose
      delivered to the target field. The radiation dose to normal tissues and organs
      was within the dose limitation. Subjects experienced mild acute toxicity. The
      main manifestations were breast edema in 22 patients, breast pain in 7, skin
      erythema in 25, general malaise in 22 and cytopenia in 8. No acute radiological
      cardiac or pulmonary injury was found. CONCLUSIONS: The results of our short-term
      follow-up showed that it is feasible to perform APBI-3DCRT for early-stage breast
      cancer after breast-conserving surgery in Chinese female patients with smaller
      breasts. However, further studies are required to elucidate its efficacy and long
      term side effects.

PMID- 21740739
TI  - Evaluation of etiological characteristics of Chinese women with recurrent
      spontaneous abortions: a single-centre study.
AB  - BACKGROUND: Various etiologies that contribute to the loss of pregnancy have been
      proposed. Despite the lack of established and uniform screening methods for
      recurrent pregnancy loss (RPL), there are several factors considered to be
      definite (or probable) causes of RPL. Data describing the etiological
      characteristics of RPL consist almost entirely of Caucasian populations. As we
      were interested in the Chinese population, the goal of this study was to
      determine the etiological characteristics of RPL in the Chinese patients.
      METHODS: The study was performed retrospectively by analyzing 1122 women with
      RPL. Patients were divided into three groups according to their number of
      pregnancy losses. Diagnostic tests included the following 9 critiria: parental
      genetics, uterine anatomy, autoimmune factors, alloimmune factors, thrombophilic
      factors, endocrine parameters, genital infection, toxoplasma, rubella,
      cytomegalovirus, herpes (TORCH) titers and RH blood groups. The criteria for
      abnormal results were defined before diagnosis. RESULTS: We found that 87.1%
      (977/1122) patients had no more than 3 abnormal aspects, and the proportion of
      total abnormal results was similar among groups. The prevalence of abnormal
      results for each test did not differ among groups, except in the cases of
      parental genetics, uterine anatomy and presence of mixed lymphocyte reaction
      blocking antibodies (MLR-Bf). Absence of MLR-Bf, as well as abnormally increased
      levels of CD3+CD19+ and CD56+CD16+ cells, was commonly detected in Chinese RPL
      patients. CONCLUSION: Immunological disorders play an important role in RPL among
      Chinese patients.

PMID- 21740740
TI  - Primary sarcoma of the ovary: clinicopathological characteristics, prognostic
      factors and evaluation of therapy.
AB  - BACKGROUND: The primary ovarian sarcoma is a very rare malignancy. The objective
      of this study was to further investigate the clinicopathologic features and
      outcome in patients with primary sarcoma of the ovary. METHODS: Between 1988 and
      2007, 24 patients with primary ovarian sarcoma who underwent treatment at Peking
      Union Medical Hospital were reviewed retrospectively. Response to treatment,
      progression and overall survival were analyzed. RESULTS: Patients with ovarian
      sarcoma had a mean age of (54.3 +/- 10.3) years, and 16 of them were
      postmenopausal. The most common symptom was abdominal pain, present in 14
      patients. Of the 24 patients, 16 patients were pathologically diagnosed as
      carcinosarcoma (known as malignant mixed mesodermal tumor (MMMT)), 2 as ovarian
      leiomyosarcoma (LS) and 6 patients as ovarian endometrial stromal sarcoma (ESS).
      The patients in optimal debulking group had a median survival period of 28 months
      and 1-year survival rate of 71%. The patients in suboptimal debulking group had a
      significantly lower median survival of 6 months (P = 0.02) and 1-year survival
      rate of 29%. Among the patients, 23 patients received chemotherapy and most of
      regimens were based on platinum, 3 patients received chemoradiation. The mean
      number of courses of combined chemotherapy was 6.6 +/- 5.0, and the response was
      unsatisfactory. The median survival for the entire group was 18.7 months. The one
      year survival rate was 58%, and two-year survival rate only 29%. CONCLUSIONS:
      Ovarian primary sarcoma has a poor overall prognosis. Optimal debulking surgery
      appears to be of prognostic significance. There is a clear need for further study
      to explore the role and the regimen of platinum-based chemotherapy in primary
      ovarian sarcoma.

PMID- 21740741
TI  - Characteristics and efficacy of modified adenomyomectomy in the treatment of
      uterine adenomyoma.
AB  - BACKGROUND: Adenomyoma is a very serious disease which influence the quality of
      life and leads to the infertility, and hysterectomy at the end. Unfortunetly, we
      still have no effective way to treat this kind of diseases. This study was aimed
      to evaluate the efficacy and surgical characteristics of modified
      adenomyomectomy. METHODS: This is a retrospective study and the subjects were
      collected in the past 5 years. We divided the subjects by the two different
      surgical procedures. Cases of adenomyoma patients who underwent conservative
      surgery, modified adenomyomectomy or wedge resection of the adenomyoma lesion
      were distributed to two groups retrospectively. Surgical characteristics, symptom
      relief, and recurrence were analysed in each group. RESULTS: General
      characteristics, including operation time, blood loss, and postoperative
      complication were similar in both groups. In the modified adenomyometomy group,
      the median follow-up time was 27.6 months and the rate of relief of dysmenorrhea
      and menorrhagia symptoms were 91.2% and 40.0%, respectively. In the wedge
      resection group, the rate of reliefe of dysmenorrhea and menorrhagia symptoms
      were 88.9% and 50.0%, respectively. Patients in both groups had statistically
      significant symptom relief, but there was no statistical difference between them.
      During the following time, ultrasonography relapse rate in modified modified
      adenomyomectomy group is significantly lower than the wedge resection group 15.0%
      vs. 69.2% (P < 0.001). The relapse rate, in terms of symptoms, was 5.0% in the
      modified adenomyomectomy group, which was similar to the relapse rate in the
      wedge resection group. In terms of reproductive outcome, 33.3% of the patients
      with infertility complications in the modified adenomyomectomy group became
      pregnant. Among them, the rate of pregnancy by assisted reproductive techniques
      was 45.5%, which was significantly higher than the rate of natural pregnancy,
      23.1% (P = 0.039). CONCLUSION: Modified adenomyomectomy appears to be a safe and
      effective operative method that shows advantages in reducing the rate of relapse
      after surgery.

PMID- 21740742
TI  - Effects of ovarian cancer G protein coupled receptor 1 on the proliferation,
      migration, and adhesion of human ovarian cancer cells.
AB  - BACKGROUND: OGR1 was found as a G-protein coupled receptor (GPCR) and proton
      sensor. Our previous studies have found that OGR1 has inhibitory effect on the
      metastasis of prostate cancer. In order to investigate the roles of OGR1 gene in
      the biological activities of ovarian cancer, we studied the OGR1 effects on
      ovarian cancer cells, HEY cells. METHODS: OGR1 gene was transfected into HEY
      cell, in which endogenous expression is low. OGR1-overxepressed cells and vector
      transfected cells were compared in different assays. Western blotting was
      employed to confirm the high expression level of OGR1. Cell proliferation was
      determined by MTT assay and cell doubling time assay. Cell migration assay
      (transwell assay) and cell adhesion assay were performed to determine the
      migration and adhesion potential of cells. Student's t test was employed for
      statistical analysis. RESULTS: Proliferation of OGR1-overexpressed cells was
      significantly reduced (P < 0.01); cell migration was significantly inhibited in
      the OGR1-transfected cells (P < 0.01); cell adhesion to extracellular matrix
      including fibronectin, vitronectin, collagen I/IV was significantly increased (P
      < 0.01). CONCLUSIONS: OGR1 expression in human ovarian cancer cells significantly
      inhibited the cell proliferation and migration, but significantly enhanced cell
      adhesion to the extracellular matrix. It indicated that OGR1 may be a tumor
      suppressor gene for ovarian cancer.

PMID- 21740743
TI  - Predictors of response to antiviral therapy in patients with chronic hepatitis C
      from Pakistani population.
AB  - BACKGROUND: Hepatitis C virus (HCV) constitutes a major public health issue
      around the world, especially in developing countries like Pakistan. In this
      study, we assessed outcome of interferon (INF) treatment in chronic hepatitis C
      patients categorized by gender, age, and viral load. METHODS: In this study, 750
      HCV positive patients with genotype 3 were selected, out of which 616 completed
      the entire treatment. Their personal history, pre-treatment HCV RNA and serum
      alanine transaminase (ALT) was quantified. Patients were treated with combination
      therapy of INF-alpha 2b three million units (thrice a week) plus ribavirin (1000 
      1200 mg per day) for 24 weeks. After 24 weeks their HCV RNA and serum ALT level
      was quantified. RESULTS: Out of the 616 patients, 391 (63.5%) responded to
      therapeutic regimen (INF-alpha 2b plus ribavirin). Among the responders, 27.1%
      were men and 36.4% were women. Best treatment response was observed in patients
      having low viral load < 8 * 10(5) IU/ml and age <= 40 years than patients having
      low viral load and age > 40 years (73.2% vs. 60.3%, P = 0.05). CONCLUSIONS:
      Better response to IFN-alpha 2b plus ribavirin was observed in patients with
      lower viral RNA and younger age. It suggests that all patients considered for
      treatment should have quantification of serum HCV RNA level. The result can be
      used to counsel patients on the likelihood of response and may influence the
      patient's decision on treatment.

PMID- 21740744
TI  - Potential predictors of non-response and super-response to cardiac
      resynchronization therapy.
AB  - BACKGROUND: Although cardiac resynchronization therapy (CRT) is already an
      established treatment, the characteristics of patients who have an excellent
      response to CRT and those who get no benefit remain to be determined. The purpose
      of this study was to search for potential predictors of both non-response and
      super-response to CRT. METHODS: Seventy-six consecutive patients who received CRT
      treatment were divided into group A (non-responders), group C (super-responders)
      and group B (responders exclusive of super-responders). Student's t test, Mann
      Whitney test, Logistic regression and receiver operating characteristic curve
      were employed to identify potential predictors among the patients' demographic
      characteristics, clinical features, several electrocardiographic parameters
      before and after CRT implantation, and their pre-implant echocardiographic
      parameters. RESULTS: Group A had the lowest 3-month left ventricular ejection
      fraction (LVEF). Group C had the smallest pre-implant left ventricular end
      diastolic dimension (LVEDD), the shortest post-implant QRS duration, the smallest
      3-month LVEDD and the highest 3-month LVEF. In addition, there was a trend of
      gradual change in percent of left bundle branch block, severity of pre-implant
      mitral regurgitation, pre-implant QRS dispersion, post-implant QRS duration as
      well as post-implant QRS dispersion from group A to group B and from group B to
      group C. Multivariable Logistic analysis revealed that only pre-implant LVEDD
      could predict CRT super-response. A pre-implant LVEDD of 68.5 mm was the cut-off
      value that identified super-responders with 87.5% sensitivity and 79.7%
      specificity. A pre-implant LVEDD of 62.5 mm identified super-responders with
      50.0% sensitivity and 89.8% specificity. CONCLUSIONS: Predictors of a CRT non
      response remain unclear at present. But it is credible that patients with a
      smaller left ventricle would have a better chance to become super-responders to
      CRT.

PMID- 21740745
TI  - Magnetic resonance spectroscopy in the diagnosis of cognitive impairment in AIDS
      patients.
AB  - BACKGROUND: The pathological abnormalities of the AIDS patients lie in the
      subcortical regions of the brain, specifically the deep white matter and basal
      ganglia, while the extent of pathology generally correlates with the severity of
      cognitive impairments in the white matter and basal ganglia. Brain metabolite
      changes of these lesions can reflect the pathological abnormalities. The purpose
      of this study was to assess the value of magnetic resonance spectroscopy (MRS) in
      the diagnosis of cognitive impairment in AIDS patients. METHODS: 3.0T MR was used
      to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI) and
      creatinine (Cr) in the frontal white matter, basal ganglia and parietal cortex of
      21 AIDS patients with dementia complex (ADC), 19 AIDS patients with
      neuroasymptomatic (NAS) and 20 seronegative (SN) controls. Then we compared the
      difference of metabolic rate between AIDS patients and SN groups. RESULTS: NAA/Cr
      (mean = 1.2502, SD = 0.1600) was significantly decreased and Cho/Cr (mean =
      1.2028, SD = 1.1655) was increased in the frontal white matter in ADC group,
      while NAA/Cr (mean = 1.5334, SD = 0.0513) was reduced in NAS group when compared
      with SN group. NAA/Cr in the basal ganglia was decreased in both ADC and NAS
      groups (mean = 1.2625, SD = 0.1615 and mean = 1.5278, SD = 0.0380, respectively).
      Cho/Cr (mean = 1.1631, SD = 0.0981) was markedly increased in ADC group. Although
      NAA/Cr, Cho/Cr and MI/Cr in the parietal cortex had a certain change in both ADC
      and NAS groups compared with SN group, the differences were not statistically
      significant. CONCLUSIONS: The brain metabolite changes of AIDS patients are
      correlated with cognitive impairments. MRS can be used as a valuable inspection
      method to assess cognitive impairments in AIDS patients.

PMID- 21740746
TI  - Noise exposure assessment with task-based measurement in complex noise
      environment.
AB  - BACKGROUND: Task-based measurement (TBM) is a method to assess the eight-hour A
      weighted equivalent noise exposure level (L(Aeq.8h)) besides dosimeter. TBM can
      be better used in factories by non-professional workers and staffs. However, it
      is still not clear if TBM is equal or similar with dosimeter for L(Aeq.8h)
      measurement in general. This study considered the measurement with dosimeter as
      real personal noise exposure level (PNEL) and assessed the accuracy of TBM by
      comparing the consistencies of TBM and dosimeter in L(Aeq.8h) measurement.
      METHODS: The study was conducted in one automobile firm among 387 workers who are
      exposed to unstable noise. Dosimeters and TBM were used to compare the two
      strategies and assess the degree of agreement and causes of disagreement.
      Worker's PNEL was measured via TBM for noise; the real PNEL was also recorded.
      The TBM for noise was computed with task/position noise levels measured via sound
      level meter and workers' exposure information collected via working diary forms
      (WDF) filled by participants themselves. Full-shift noise exposure measurement
      via personal noise dosimeters were taken as the real PNEL. General linear model
      (GLM) was built to analyze the accuracy of TBM for noise and the source of
      difference between TBM for noise and real PNEL. RESULTS: The L(Aeq.8h) with TBM
      were slightly higher than the real PNELs, except the electricians. Differences of
      the two values had statistical significance in stamping workers (P < 0.001),
      assembly workers (P = 0.015) and welding workers (P = 0.001). The correlation
      coefficient of L(Aeq.8h) with TBM and real PNELs was 0.841. Differences of the
      two results were mainly affected by real PNEL (F = 11.27, P = 0.001); and work
      groups (F = 3.11, P < 0.001) divided by jobs and workshops were also independent
      factors. PNEL of workers with fixed task/position ((86.53 +/- 8.82) dB(A)) was
      higher than those without ((75.76 +/- 9.92) dB(A)) (t = 8.84, P < 0.01). Whether
      workers had fixed task/position was another factor on the accuracy of TBM for
      noise (F = 4.36, P = 0.038). CONCLUSION: TBM for noise has acceptable accuracy on
      workers' PNEL measurement. The accuracy is affected by job categories, workshops
      and variability of task/position. TBM for noise can yield a relatively
      conservative result of worker's PNEL in most cases, so it can be used to measure
      and assess workers' real PNEL.

PMID- 21740747
TI  - Haemostatic agents of the gelatin matrix for a large liver wound by percutaneous
      injection without pressure under the guidance of contrast-enhanced ultrasound.
AB  - BACKGROUND: The non-operation treatment of intra-abdominal trauma guided contrast
      enhanced ultrasound (CEUS) is one of the hottest research topic.
      Gelatin/thrombin/calcium (GTC) was developed as a novel haemostatic agent for non
      operable intra-abdominal trauma. We hypothesized that GTC can achieve haemostasis
      (without the use of pressure) within a short time in a large wound model by
      percutaneous injection under CEUS guidance. METHODS: Forty Wister rats received
      large liver injuries by haemostatic clamp and were randomly divided into four
      groups, according to the haemostatic agent used. These included normal saline
      (NS) group A, lyophilising thrombin powder (LTP) group B, GTC group C, and
      absorbable alpha-cyanoacrylate (ACNA) group D. Each injury site was treated with
      one of the above materials and total bleeding time was recorded. All liver wounds
      were evaluated using CEUS at three periods: pre-injury, injury and post
      treatment. The liver wounds were also evaluated by histology 3, 6, and 9 days
      after injury and the extents of abdominal adhesions were recorded. RESULTS: The
      sensitivity of CEUS (100%) in detecting blunt traumatic liver lesions was
      significantly higher than conventional ultrasound (42.5%). Bleeding times at the
      injury site in the GTC group C ((129.3 +/- 14.0) seconds) and ACNA group D ((5.2
      +/- 1.0) seconds) were significantly shorter than those in the NS group A ((369.5
      +/- 48.8) seconds, P < 0.01) and LTP group B ((324.7 +/- 52.22) seconds, P <
      0.01). The LTP group B showed no significant difference compared with the NS
      group A. Gross examination of liver tissue revealed that there were fewer intra
      abdominal adhesions in the GTC group C (10%) than in the ACNA group D (100%).
      Histopathologic examination showed that GTC was completely absorbed after nine
      days. CONCLUSIONS: GTC, delivered by percutaneous injection under CEUS, may
      achieve haemostasis (without the use of pressure) within a short time in a large
      wound model. GTC is absorbable and may prevent intra-abdominal adhesions.
      Therefore, it may be the optimal choice for first aid treatment of large
      abdominal wounds in the setting of blunt trauma.

PMID- 21740748
TI  - In vitro induction of specific anti-tumoral immunity against laryngeal carcinoma
      by using human interleukin-12 gene-transfected dendritic cells.
AB  - BACKGROUND: Objective evaluation of the antitumor effect of interleukin-12 (IL
      12) gene-transfected dendritic cell (DC) vaccine on laryngeal carcinoma requires
      in vivo and in vitro tests. The aim of this study was to investigate the function
      of IL-12 gene transfected DC at initiating specific immune response to laryngeal
      carcinoma in vitro. METHODS: Recombinant adenovirus with IL-12 gene was
      constructed. DCs were isolated from the peripheral blood of patients with
      laryngeal carcinoma, pulsed with tumor lysate of laryngeal carcinoma cells
      (DC+Ag), and transfected with IL-12 (DC-IL-12+Ag). The cells pheotypes including
      CD83, CD86 and HLA-DR on surface of DCs were assayed by flow cytometry (FCM). The
      concentration of IL-12 in culture supernatant of DCs and interferon gamma (IFN
      gamma) in culture supernatant of T cells cocultured with DCs were quantified by
      ELISA. Methyl thiazolys tetrazolium (MTT) was used to evaluate proliferation of
      autologous T lymphocytes and activation of cytotoxic T lymphocytes (CTL)
      stimulated by IL-12-transfected DCs pulsed with tumor lysate against laryngeal
      carcinoma cells. RESULTS: The recombinant adenovirus expressing IL-12 gene was
      constructed successfully. Gene-transfected DC plused with tumor lysate with IL-12
      (DC-IL-12+Ag) expressed higher level of CD83, CD86 and produced higher level of
      IL-12 than untransfected DCs (DC+Ag) (CD83: (60.2 +/- 1.8)% vs. (50.7 +/- 1.2)%,
      P < 0.05; CD86: (88.9 +/- 2.1)% vs. (78.2 +/- 3.9)%, P < 0.05; IL-12: (262.5 +/-
      3.0) ng/L vs. (103.8 +/- 5.1) ng/L, P < 0.05). The proliferation of autologous T
      lymphocytes and production of IFN-gamma stimulated by DC transfected with IL-12
      were more obviously than untransfected DCs. Cytotoxicity of CTL stimulated by IL
      12-transfected DC pulsed with tumor lysate against laryngeal carcinoma cells were
      significantly stronger than stimulated by untransfected DC. CONCLUSION: It is a
      promising approach for IL-12-transfected DC pulsed with tumor lysate to increase
      the antitumoral effect.

PMID- 21740749
TI  - Regional cerebral blood flow in children with autism spectrum disorders: a
      quantitative 99mTc-ECD brain SPECT study with statistical parametric mapping
      evaluation.
AB  - BACKGROUND: Autism spectrum disorders (ASD), which include autism, asperger
      syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD
      NOS), are devastating neurodevelopmental disorders of childhood resulting in
      deficits in social interaction, repetitive patterns of behaviors, and restricted
      interests and activities. Single photon emission computed tomography (SPECT) is a
      common technique used to measure regional cerebral blood flow (rCBF). Several
      studies have measured rCBF in children with ASD using SPECT, however, findings
      are discordant. In addition, the majority of subjects used in these studies were
      autistic. In this study, we aimed to investigate changes in rCBF in children with
      ASD using SPECT. METHODS: A Technetium-99m-ethyl cysteinate dimmer (99m)Tc-ECD)
      brain SPECT study was performed on an ASD group consisting of 23 children (3
      girls and 20 boys; mean age (7.2 +/- 3.0) years) who were diagnosed according to
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
      criteria and an age-matched control group with 8 children (1 girl and 7 boys,
      mean age (5.5 +/- 2.4) years). Image data were evaluated with Statistical
      Parametric Mapping, 5th version (SPM5). A Student's t test for unpaired data was
      used to compare rCBF and asymmetry in the autism and corresponding control group.
      The covariance analysis, taking age as covariance, was performed between the ASD
      and control group. RESULTS: There was a significant reduction in rCBF in the
      bilateral frontal lobe (frontal poles, arcula frontal gyrus) and the bilateral
      basal ganglia in the autism group, and a reduction in the bilateral frontal,
      temporal, parietal, legumina nucleus and cerebellum in the AS group compared to
      the control. In addition, asymmetry of hemispheric hypoperfusion in the ASD group
      was observed. Inner-group comparison analysis revealed that rCBF decreased
      significantly in the bilateral frontal lobe (42.7%), basal nucleus (24.9%) and
      temporal lobe (22.8%) in the autism group, and in the bilateral cerebellum
      (22.8%), basal nucleus (19.3%) and right thalamencephalon (16.6%) in the AS group
      (P < 0.05). CONCLUSIONS: The decrease in rCBF in ASD is a global event, which
      involves the bilateral frontal, temporal, limbic system and basal ganglias.
      Asymmetry of hemispheric hypoperfusion was more obvious in the AS group than the
      autism group, which indicates a different neurobiological mechanism from that of
      autism.

PMID- 21740750
TI  - A serum metabonomic study on the difference between alcohol- and HBV-induced
      liver cirrhosis by ultraperformance liquid chromatography coupled to mass
      spectrometry plus quadrupole time-of-flight mass spectrometry.
AB  - BACKGROUND: Liver cirrhosis is the fatal consequence of chronic hepatitis, making
      early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard
      diagnostic method for liver cirrhosis, although its use in a broad population
      with alcoholism or hepatitis B virus (HBV) infection remains difficult. In this
      study, we used a metabonomic approach to detect potential biomarkers for early
      diagnosis of liver cirrhosis. METHODS: Serum specimens were collected
      prospectively from normal control subjects (n = 22) and patients with alcoholic
      cirrhosis (n = 18) or HBV-induced cirrhosis (n = 19). The serum metabonome was
      analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass
      spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were
      normalized and processed using principal component analysis (PCA) and partial
      least squares discrimination analysis (PLS-DA). RESULTS: Significant differences
      in the metabonomics among the three groups were observed. Lysophosphatidyl
      cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC
      C20:5) were decreased in the serum of patients with hepatic cirrhosis, whereas
      bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and
      stearamide were increased in the serum of patients with hepatic cirrhosis. These
      metabolites are considered "common" biomarkers for hepatic cirrhosis. Oleamide
      and myristamide were increased in the serum of patients with alcoholic cirrhosis
      but decreased in those with HBV-induced cirrhosis. These could be specific
      biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic
      cirrhosis. CONCLUSIONS: There are significant metabonomic differences between
      alcohol- and HBV-induced liver cirrhosis. Metabonomics is a top-down systems
      biology tool for conducting research on clinical problems.

PMID- 21740751
TI  - Efficacy and safety of transcatheter chemoembolization of the internal thoracic
      artery in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Embolization of collateral arteries is important for transcatheter
      hepatic arterial chemoembolization (TACE) in patients with hepatocellular
      carcinoma (HCC). We evaluated the efficacy and safety of TACE, and the prevention
      and management of complications among patients in whom the internal thoracic
      artery (ITA) was involved. METHODS: A total of 3614 cases of HCC were treated
      with 12 645 TACEs and 211 of these cases were given ITA angiography, including
      156 cases of which the ITA was involved. We performed 562 TACEs in the 156 cases.
      We analyzed imaging examinations, types of embolization, and the incidence,
      prevention, and treatment of complications. RESULTS: The ITA was successfully
      embolized in 156 cases. Angiography of the ITA showed that the major trunks were
      thickened with an increased number of branching vessels, contributing to
      intrahepatic and extrahepatic tumor blood supply. Different embolization methods
      were selected according to the blood supply, to effectively embolize the tumor
      and mitigate or avoid serious complications. TACE with ITA embolization extended
      the mean interval time between two treatments from 2.54 months (1 - 17 months) to
      4.23 months (1 - 30 months) compared with that without ITA embolization. The ITA
      supplied the HCC in the following instances: HCC was located in the ventral
      hepatic area and abutted the diaphragm (P = 0.0064) and repeated TACE (P =
      0.0003). The survival rate of TACE with ITA embolization for HCC was better than
      TACE without ITA embolization (P < 0.00001). CONCLUSIONS: In cases with massive
      HCC or nodular HCC, the ITA may be involved in supplying blood to the tumor. This
      occurs when the tumor is positioned in the ventral hepatic area and abuts the
      diaphragm (S2, S4, and S8), and especially if cases have a previous history of
      TACE. In this case series, embolization was effective, extended the mean interval
      time of interventional therapy, and prolonged survival time.

PMID- 21740752
TI  - Treatment of severe bone deficiency in acetabular revision surgery using a
      reinforcement device and bone grafting.
AB  - BACKGROUND: Severe acetabular bone deficiency is a major challenge in acetabular
      revision surgery. Most cases require reconstruction of the acetabulum with bone
      grafting and a reinforcement device. The purpose of this study was to evaluate
      the results of this procedure for severe acetabular bone deficiency in acetabular
      revision surgery. METHODS: This study involved 12 patients (2 males and 10
      females) with severe acetabular bone defects who underwent implantation of a
      reinforcement device (ring or cage) and bone grafting between February 2003 and
      October 2008. Using the Paprosky classification, 2 cases were Paprosky IIC, 6
      were IIIA, and 4 were IIIB. The mean age at the time of surgery was 63.0 years
      (range, 46 - 78 years). During revision surgery, a reinforcement ring was
      implanted in 6 patients, and a cage in 6 patients. The clinical and radiographic
      results were evaluated retrospectively. The mean duration of follow-up was 37
      months (range, 9 - 71 months). RESULTS: The average Harris Hip Score improved
      from 35.2 preoperatively to 82.9 at the time of the final follow-up visit. The
      results were excellent in 8 hips (66.7%), good in 2 (16.7%), and fair in 2
      (16.7%). Osteolysis was found in 1 case, but did not worsen. Three patients had
      yellow wound effusion, with healing after administration of dressing changes,
      debridement, and antibiotics. Dislocation occurred in a 62-year-old woman. Closed
      reduction was performed, and dislocation did not recur. There was no evidence of
      intraoperative acetabular fracture, nerve injury, ectopic ossification, aseptic
      loosening, or infection. CONCLUSION: Reconstruction with a reinforcement device
      and bone grafting is an effective approach to the treatment of acetabular bone
      deficiency in acetabular revision surgery, given proper indications and
      technique.

PMID- 21740753
TI  - Effect of low-energy shock waves in microfracture holes in the repair of
      articular cartilage defects in a rabbit model.
AB  - BACKGROUND: Microfracture is a type of bone marrow stimulation in arthroscopic
      cartilage repair. However, the overall concentration of the mesenchymal stem
      cells is quite low and declines with age, and in the end the lesion is filled by
      fibrocartilage. The aim of this research was to investigate a novel method of
      enhancing microfracture by determining whether low-energy shock waves in
      microfracture holes would facilitate cartilage repair in a rabbit model. METHODS:
      Full-thickness cartilage defects were created at the medial femoral condyle of 36
      mature New Zealand white rabbits without penetrating subchondral bone. The
      rabbits were randomly divided into three groups. In experimental group A, low
      energy shock-wave therapy was performed in microfracture holes (diameter, 1 mm)
      at an energy flux density (EFD) of 0.095 mJ/mm2 and 200 impulses by DolorClast
      Master (Electro Medical Systems SA, Switzerland) microprobe (diameter, 0.8 mm).
      In experimental group B, microfracture was performed alone. The untreated rabbits
      served as a control group. At 4, 8, and 12 weeks after the operations, repair
      tissues at the defects were analyzed stereologically, histologically, and
      immunohistochemically. RESULTS: The defects were filled gradually with repair
      tissues in experimental groups A and B, and no repair tissues had formed in the
      control group at 12 weeks. Repair tissues in experimental group A contained more
      chondrocytes, proteoglycans, and collagen type II than those in experimental
      group B. In experimental group B, fibrous tissues had formed at the defects at 8
      and 12 weeks. Histological analysis of experimental group A showed a better
      Wakitani score (P < 0.05) than in experimental group B at 8 and 12 weeks after
      the operation. CONCLUSIONS: In the repair of full-thickness articular cartilage
      defects in rabbits, low-energy shock waves in microfracture holes facilitated the
      production of hyaline-like cartilage repair tissues more than microfracture
      alone. This model demonstrates a new method of improving microfracture and
      applying shock waves in vivo. However, longer-term outcomes require further
      study.

PMID- 21740754
TI  - Ultrasonic destruction of albumin microbubbles enhances gene transfection and
      expression in cardiac myocytes.
AB  - BACKGROUND: It has been proven that ultrasonic destruction of microbubbles can
      enhance gene transfection efficiency into the noncardiac cells, but there are few
      reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear;
      whether the characteristic of microbubbles can affect the gene transfection
      efficiency or not is still controversial. This study was designed to investigate
      whether the ultrasound destruction of gene-loaded microbubbles could enhance the
      plasmids carried reporter gene transfection in primary cultured myocardial cell,
      and evaluate the effects of microbubbles characteristics on the transgene
      expression in cardiac myocytes. METHODS: The beta-galactosidase plasmids attached
      to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA)
      and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared.
      The gene transfection into cardiac myocytes was performed in vitro by naked
      plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles
      and calcium phosphate precipitation, and then the gene expression and cell
      viability were analyzed. RESULTS: The ultrasonic destruction of gene-loaded
      microbubbles enhanced gene expression in cardiac myocytes compared with naked
      plasmid transfection ((51.95 +/- 2.41) U/g or (29.28 +/- 3.65) U/g vs. (0.84 +/-
      0.21) U/g, P < 0.01), and ultrasonic destruction PESDA resulted in more
      significant gene expression than ASDA ((51.95 +/- 2.41) U/g vs. (29.28 +/- 3.65)
      U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate
      precipitation gene transfection enhanced beta-galactosidase activity nearly 8
      fold compared with calcium phosphate precipitation gene transfection alone
      ((111.35 +/- 11.21) U/g protein vs. (14.13 +/- 2.58) U/g protein, P < 0.01). Even
      6 hours after calcium phosphate precipitation gene transfection, ultrasound
      mediated microbubbles destruction resulted in more intense gene expression
      ((35.63 +/- 7.65) U/g vs. (14.13 +/- 2.58) U/g, P < 0.05). CONCLUSIONS:
      Ultrasonic destruction of microbubbles might be a promising method for the
      delivery of non-viral DNA into cardiac myocytes, and the gene tranfection is
      related to the characteristics of microbubbles.

PMID- 21740755
TI  - A ten-year audit of traditional Chinese medicine and other natural product
      research published in the Chinese Medical Journal (2000-2009).
AB  - BACKGROUND: Clinical research encompasses a wide variety of disciplines.
      Traditional Chinese medicine (TCM) and natural product research have made great
      contributions to preventing and treating illness. The number and content of
      original research reports evaluating TCM and natural products have not previously
      been described. Information in this area will identify areas of relative strength
      and weakness in terms of knowledge gaps with respect to clinical conditions and
      natural product remedies. METHODS: Original research reports (i.e. original
      articles, brief reports, and research letters) published in the Chinese Medical
      Journal (CMJ) from January 2000 to December 2009 evaluating TCM and other natural
      products were reviewed. The United Kingdom Clinical Research Collaboration (UK
      CRC) Health Research Classification System was used to analyze the type of health
      research conducted. Further analysis on the major illnesses addressed and the
      major herbal components utilized was conducted. RESULTS: One hundred and
      seventeen original research reports involving TCM or other natural products were
      identified, comprising 3.82% of the CMJ output in the period covered by this
      study. Of the different materia medica described in these reports, 74.4% were
      derived exclusively from plant material, 10.3% from animals, 3.4% from fungi,
      1.7% from minerals, and 10.3% were of mixed (plant/animal/fungal/mineral)
      composition. Twelve herbs were investigated exclusively or were constituents of
      66/87 (75.9%) of the plant-based materia medica investigated. Panax ginseng was
      the most commonly investigated herb or constituent (14/87, 16.1%), followed by
      Astragalus membranaceus (9/87, 10.3%), Coptis chinensis/Berberis spp. (7/87,
      8.0%) and Rheum spp. (7/87, 8.0%). Four UK-CRC health categories accounted for
      the majority of TCM and other natural product research (cancer, 20.9%;
      cardiovascular, 19.2%; oral/gastrointestinal, 9.8%; and inflammatory/immune,
      9.0%). The most common research activity was "development of treatments and
      therapeutic interventions", which was undertaken by 103/117 (88.0%) of the
      research investigations reported. Human clinical trials involving natural
      products accounted for only 5.31% of the reported studies. CONCLUSIONS: This is a
      relatively early systematic description of published research from a single
      journal related to TCM and other natural products. The majority of the research
      reports described preliminary findings and very few controlled clinical trials in
      human subjects were reported. Further applied studies will be required to
      demonstrate the clinical effectiveness, utility and cost-effectiveness of TCM and
      natural products in clinical practice. The UK-CRC health research classification
      system is a useful tool for evaluating published research output and could be
      applied to describe the output from other journals, national and provincial
      funding bodies, charities, and non-governmental organizations involved in
      supporting health-related research.

PMID- 21740756
TI  - Treatment strategies in acute myeloid leukemia.
AB  - OBJECTIVE: To summarize the risk stratification and current treatment strategies
      for acute myeloid leukemia (AML) and discuss the role of emerging novel agents
      that might be applied in future clinical trials. DATA SOURCES: The data in this
      article were collected from PubMed database with relevant English articles
      published from 1991 to 2009. STUDY SELECTION: Articles regarding the risk
      stratification and therapeutic options of AML, as well as the characteristics of
      leukemic stem cells were selected. RESULTS: AML is a heterogeneous disease with
      variable clinical outcome dependent on several prognostic factors, including age,
      cytogenetics and molecular markers. The advances in the understanding of AML
      pathogenesis and development will generate potential novel agents that might
      improve the treatment results of standard chemotherapy. CONCLUSION: Deeper
      insight into the multiple transforming events of AML may aid us in designing
      combinations of small molecule inhibitors based on the individual patient
      characteristics.

PMID- 21740757
TI  - Quantitative analysis of host cells growing into canine homograft valved aortic
      and pulmonary artery.
AB  - BACKGROUND: Cryopreserved conduit valved homografts (CVH) have been widely used
      in surgical treatment of cardiac disease. This study aimed to determine the
      extent of host cell ingrowth and the durability and immunogenicity of CVH, and to
      compare the performance of CVH stored at 4 degrees C and CVH cryopreserved in
      liquid nitrogen at -196 degrees C. METHODS: Heterotopic transplants of canine CVH
      stored at 4 degrees C (n = 14) and cryopreserved in liquid nitrogen (n = 14) were
      made onto the abdominal aorta of recipient dogs. Animals were sacrificed at 7 and
      15 days and at 1, 3, 6, 9, and 12 months after transplantation to excise the
      implanted CVHs. Tissue DNA extraction and quantitative polymerase chain reaction
      (PCR) were performed to calculate the ratio of donor cells and host cells in the
      CVH. The tissue viability of CVH after implantation was analyzed by detecting
      alkaline fibroblast growth factor 2 (FGF-2) using immunohistochemical staining
      and by observation under transmission electron microscope and scanning electron
      microscope. RESULTS: All the animals survived and recovered well. There were few
      repopulating host cells (0.04% - 0.83%) in the implanted CVH at 7 or 15 days. The
      ratio of ingrowing host cells into the CVH continued rising after implantation
      and reached 40% - 47% in the 12th month postoperation. Histology, transmission
      electron microscopy and FGF-2 immunohistochemical staining indicated that
      fibroblasts and the host's endothelial cells were the main cellular elements
      invading the CVH. There were no significant differences in results between CVH
      stored at 4 degrees C and CVH cryopreserved in liquid nitrogen. CONCLUSIONS: Host
      cells growing into CVH are very important for maintaining the long-term structure
      and function of the implanted CVH. There is no significant difference between CVH
      storing at 4 degrees C or in liquid nitrogen in regard to the ingrowth of host
      cells or of morphologic features after CVH allografting.

PMID- 21740758
TI  - AIDS complicated with intestinal lymphoma: X-ray radiology, CT scan and
      pathological findings.
AB  - BACKGROUND: The non-Hodgkin's lymphoma is the AIDS symbol of tumor, with high
      incidence and poor prognosis. The purpose of this study was to investigate the
      radiological demonstrations of AIDS complicated by intestinal lymphoma and its
      pathological mechanism. METHODS: CT scan and pathological data of 3 cases of AIDS
      complicated by intestinal lymphoma were retrospectively analyzed. All the 3 cases
      received CT diagnostic scanning, including 2 receiving barium enema radiography
      after lower gastrointestinal tract cleansing, 1 receiving laporotomy to obtain
      partial thickened intestinal canal for histopathology and 1 with autopsy for
      histopathological analysis. RESULTS: Intestinal canal lymphoma occurred at the
      left intestinal canal in 2 cases and at the right intestinal canal in the other
      case, with manifestations of unevenly thickened intestinal canal wall, narrowed
      canal lumen and filling defect. It was pathologically classified as B cell
      lymphoma. CONCLUSIONS: AIDS complicated by B cell lymphoma has manifestations of
      unevenly thickened intestinal canal wall and narrowed canal lumen, which are non
      specific. It should be differentiated from other tumors of intestinal canal in
      its diagnosis.

PMID- 21740759
TI  - Treatment of urinary lithiasis following kidney transplantation with
      extracorporeal shock-wave lithotripsy.
AB  - BACKGROUND: The incidence of urinary lithiasis following kidney transplantation
      is very low, and decision-supporting data are not available. The aim of this
      study was to review the diagnosis and treatment of urinary lithiasis following
      kidney transplantation, which is of realistic significance to reduce urinary
      lithiasis following kidney transplantation, prolong the survival of renal
      allografts. METHODS: The incidence, diagnosis and treatment of urinary lithiasis
      in ten patients following kidney transplantation were analyzed retrospectively.
      Seven out of these patients had stones sized approximately 0.4 - 1.1 cm, and they
      were treated with low-voltage, low-frequency extracorporeal shock-wave
      lithotripsy (ESWL). Two patients had stones sized < 0.3 cm and they underwent
      cystoscopy and ureteroscopy. The ureteral catheter endoscopes were inserted in a
      retrograde manner to mobilize stones repeatedly. After elimination of
      obstruction, a ureteral double J stent was indwelt. One patient had a pelvic
      stone (1.2 cm), which was removed surgically. RESULTS: The major clinical
      manifestations were hematuria, oliguria or anuria. Some patients were
      asymptomatic and they were diagnosed through laboratory tests and imaging
      examinations, e.g., ultrasonography. After elimination of obstruction, subjective
      symptoms disappeared in all patients, and the function of renal allografts
      recovered. A six-month follow-up indicated no remnant stones or lithiasis
      relapse. CONCLUSIONS: The diagnosis and treatment of renal allograft lithiasis
      are challenging. After prompt and appropriate treatment, the prognosis was
      satisfactory, and permanent renal functional impairment did not occur in most
      patients.

PMID- 21740760
TI  - Resection of a giant renal angiomyolipoma in a solitary kidney with preoperative
      arterial embolization.
AB  - Renal angiomyolipoma is a type of benign tumor that occurs sporadically in
      addition to being associated with tuberous sclerosis. Preoperative embolization
      of large tumors is important to avoid excessive blood loss during surgery. We
      reported a patient with a 5505-g giant renal angiomyolipoma in a solitary kidney.
      The patient was treated with preoperative embolization and radical nephrectomy
      without complications. This type of treatment for an enormous angiomyolipoma can
      reduce the risk of uncontrolled hemorrhage caused by rupture of the tumor during
      the operation and should be considered for the treatment of similar tumors.

PMID- 21740761
TI  - Surgical strategy for pulmonary atresia with ventricular septal defect and major
      aortopulmonary collateral arteries.

PMID- 21740762
TI  - Renal subcapsular haematoma: an unusual complication of renal artery stenting.
AB  - After successful renal artery angioplasty and stent placement, a patient in a
      fully anticoagulated state developed hypotension and flank pain. Computed
      tomography (CT) of the abdomen revealed a large renal subcapsular haematoma which
      was successfully managed conservatively without embolotherapy and surgical
      intervention. To prevent hemorrhage after renal artery stenting, it is necessary
      to underscore the importance of reducing the contrast volume and pressure of
      angiography, controlling systemic blood pressure, and monitoring guide wire
      position at all times.

PMID- 21740763
TI  - Impact of myocardial perfusion imaging on in-hospital coronary angiography and
      revascularization of patients with suspected coronary artery disease.
AB  - BACKGROUND: Noninvasive cardiac imaging is now central to the diagnosis and
      management of patients with moderate probability for coronary artery disease. The
      aim of this study was to assess the impact of stress myocardial perfusion single
      photon emission computerized tomography (SPECT) on in-hospital coronary
      angiography and revascularization for such patients. METHODS: Between January
      2005 and June 2007, 1053 consecutive in-hospital patients (423 women, the average
      age of (57.2 +/- 11.2) years) with suspected coronary artery disease but without
      any prior interventional treatment were retrospectively analyzed. All patients
      underwent a 2-day stress/rest (99m)Tc-methoxyisobutylisonitrile (MIBI) myocardial
      perfusion SPECT, including 984 exercise test and 69 adenosine test. RESULTS:
      Overall, stress/rest myocardial perfusion SPECT was normal in 973 patients
      (92.4%) and abnormal in 80 patients (7.6%). A total of 190 patients underwent
      coronary angiography, 46 underwent percutaneous coronary intervention and 10
      coronary artery bypass grafting during hospitalization. From the whole
      perspective, only 14.7% of patients with normal SPECT underwent coronary
      angiography, so did 58.8% of patients with abnormal SPECT (chi(2) = 97.0, P <
      0.001); furthermore, the rates of revascularization in patients with normal and
      abnormal SPECT were 2.8% and 36.3%, respectively (27 out of 973 vs. 29 out of 80,
      chi(2) = 157.9, P < 0.001). The extent and severity of ischemia did not add more
      predictive value for subsequent coronary angiography, but did have impact on
      revascularization. Multivariate analysis showed that reversible perfusion defect
      was the most predictive variable for referral rate to coronary angiography (odds
      ratio = 7.5, P < 0.001). CONCLUSIONS: Abnormal myocardial perfusion SPECT is a
      powerful referral for in-hospital coronary angiography and revascularization
      during the same hospitalization. Thus, stress/rest SPECT is an effective
      gatekeeper for early coronary angiography and invasive treatment for patients
      with suspected coronary artery disease.

PMID- 21740764
TI  - Stereotactic aspiration and thrombolysis of spontaneous intracerebellar
      hemorrhage.
AB  - BACKGROUND: Spontaneous intracerebellar hemorrhage (SCH) accounts for 10% of
      intracerebral hemorrhages. Up to now stereotactic aspiration and thrombolysis of
      SCH was less reported. The aim of this study was to assess the effect and
      feasibility of the method, and to refine the clinical protocol. METHODS: Eighteen
      patients with SCH were treated by stereotactic aspiration and thrombolysis and
      reviewed in this report. The 3-mm axial stereotactic computed tomography slices
      throughout the hematoma were obtained. Those images were then transferred to the
      workstation. The trajectory of catheter was designed to go through the main axis
      of the hematoma. Under local anesthesia a catheter was directed stereotactically
      into the hematoma through a burr hole. Hematoma thrombolysis and clot drainage
      was followed by instillation of urokinase (10,000 U) every 12 hours. The catheter
      was removed when the majority of hematoma was evacuated. RESULTS: Initial SCH
      volume was reduced by an average of 86% and the average final hematoma volume was
      2.8 ml. At 3-month follow-up, 13 patients (72%) had achieved good recovery. At 6
      month follow-up, 12 patients (67%) had achieved good recovery. CONCLUSION:
      Stereotactic aspiration and thrombolysis of SCH was a simple, feasible and
      effective method to treat moderate and some benign SCH that less respond to
      medical treatment.

PMID- 21740765
TI  - Effect of intensive blood glucose control on quality of life in elderly patients
      with type 2 diabetes in Anhui Province.
AB  - BACKGROUND: Intensive blood glucose control is proven to be associated with the
      diabetic microvascular and macrovascular complications, which could affect
      quality of life (QOL). This study was performed to determine the effects of
      intensive glucose control therapy on QOL of elderly patients with type 2 diabetes
      in Anhui Province. METHODS: Ninety-seven elderly patients with type 2 diabetes in
      Anhui were randomly assigned to standard treatment group and intensive therapy
      group. All patients were followed up for five years on average. Correlated
      information has been collected during the regular follow-up. RESULTS: Patients
      with microvascular complications reported significantly lower European Quality of
      Life-5 Dimensions (EQ-5D) scores and had more problems with usual activities,
      pain and anxiety than those without complications (P < 0.05). Patients having
      experienced hypoglycemic episodes had significantly more problems with anxiety
      than those without hypoglycemic episodes (P < 0.05). No significant difference
      was detected in all dimensions in quality of life, as well as in Visual Analog
      Scale score between two groups (P > 0.05). There was no significant difference in
      quality of life at the fifth year compared with that of the first year in both
      groups. Women had more feelings of pain and anxiety than men (P < 0.05) and
      longer disease course was associated with increased levels of pain and anxiety (P
      < 0.05), as well as with lower QOL. In addition, patients with higher body mass
      index (BMI) had more problems with daily activities than patients with lower BMI
      (P < 0.05). CONCLUSIONS: Anxiety is common in elderly diabetic patients and they
      experienced frequent hypoglycemic episodes. Diabetic vascular complications
      significantly affect QOL of the patients. Intensive glucose control has no
      significant effect on QOL of the diabetic patients. Female, older age, long
      disease course, less education and high BMI are all factors caused reduced QOL
      and patients with these factors should be given more psychological support.
      Frequent mild hypoglycemic episodes do not cause impaired function of the central
      nervous system.

PMID- 21740766
TI  - Characterization of human metapneumovirus from pediatric patients with acute
      respiratory infections in a 4-year period in Beijing, China.
AB  - BACKGROUND: Human metapneumovirus (hMPV) was discovered by scientists in the
      Netherlands as a novel respiratory virus in 2001 and had been found in children
      with acute respiratory tract infections (ARTI) in China. The objective of this
      study was to determine the importance of hMPV infection in children in Beijing
      and the genotypes of the circulating virus by the surveillance during a four
      consecutive-year period. METHODS: Clinical specimens collected from children with
      ARTI from January 2006 to December 2009 were tested for hMPV by RT-PCR using
      primers targeting the matrix (M) gene, followed by genotyping of hMPV directly
      from positive samples by diplex PCR with primers for glycoprotein (G) genes.
      Sequence analysis was used for genotyping of those un-typable samples. Common
      respiratory viruses in these clinical specimens were tested by virus isolation
      and antigen detection, in addition to hMPV detection. RESULTS: Of 4730 tested
      specimens, 191 (4.0%) were positive for hMPV and 62.8% of 191 were identified as
      genotype A. The positive rate of hMPV from hospitalized patients was higher than
      that from outpatients each year. Most of hMPV positive children were under five
      years old. The peak of hMPV activity mostly occurred in late spring and
      overlapped with or followed that of respiratory syncytial virus (RSV) and
      followed by parainfluenza virus 3. Of hMPV infected cases, 68.6% were lower
      respiratory tract infection, among which 79.4% were hospitalized, and upper
      respiratory tract infection was diagnosed for 31.4% of hMPV infected children.
      The 9.4% of hMPV positive samples were found to co-exist with other respiratory
      viruses. CONCLUSIONS: hMPV was an important pathogen for ARTI in pediatric
      patients, especially those under five years old. Both genotypes A and B
      circulated simultaneously in Beijing.

PMID- 21740767
TI  - Maternal periconceptional consumption of pickled vegetables and risk of neural
      tube defects in offspring.
AB  - BACKGROUND: Maternal exposure to nitrate, nitrite, and N-nitroso compounds from
      drinking water or diet has been associated with an increased risk of neural tube
      defects (NTDs) in some studies. Pickled vegetables contain relatively large
      amounts of nitrite and N-nitroso compounds. We examined the association between
      maternal periconceptional consumption of pickled vegetables and NTDs in Shanxi
      Province of northern China. METHODS: Data were derived from a population based
      case-control study of major external birth defects in four counties of Shanxi
      Province. Participants included 519 NTDs cases identified between 2003 and 2007
      and 694 healthy controls. Exposure information was collected within 1 week after
      delivery. Multivariable non-conditional Logistic regression model was used to
      estimate the adjusted odds ratio (OR) controlling for potential confounding
      variables. RESULTS: The risk of NTDs was positively associated with the frequency
      of the consumption of pickled vegetables by the mother. Compared with pickled
      vegetables consumption at < 1 meal/week, the adjusted OR for consumption at 1 -
      3, 4 - 6, and > 6 meals/week were 1.3 (95% confidence interval (CI): 1.0, 1.8),
      1.9 (1.1, 3.2), and 3.6 (1.9, 6.9), respectively. A protective effect was found
      for maternal meat consumption at >= 1 meal/week (adjusted OR: 0.6, 95%CI: 0.4,
      0.7) and egg or milk consumption at >= 1 meal/week (adjusted OR: 0.6, 95%CI: 0.4,
      0.8). CONCLUSION: Maternal periconceptional consumption of pickled vegetables may
      increase the risk for NTDs in Shanxi Province.

PMID- 21740768
TI  - Association of nicotinic acetylcholine receptor subunit alpha-4 polymorphisms
      with smoking behaviors in Chinese male smokers.
AB  - BACKGROUND: It has been reported that the nicotinic acetylcholine receptor
      subunit alpha4 gene (CHRNA4) might be associated with smoking behaviors in the
      previous studies. Up to now, there are few reports on the relationship between
      CHRNA4 and smoking initiation. In this study, we tried to explore the role of two
      polymorphisms in CHRNA4 (rs1044396 and rs1044397) in smoking initiation and
      nicotine dependence in Chinese male smokers. METHODS: Nine hundred and sixty-six
      Chinese male lifetime nonsmokers and smokers were assessed by the Fagerstrom test
      for nicotine dependence (FTND), smoking quantity (SQ) and the heaviness of
      smoking index (HSI). All subjects were divided into four groups based on their
      tobacco use history and the FTND scores. The polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) was performed to find two
      polymorphisms of CHRNA4 in these subjects. RESULTS: The chi(2) test showed that
      rs1044396 was significantly associated with smoking initiation (chi(2) = 4.65, P
      = 0.031), while both rs1044396 and rs1044397 were significantly associated with
      nicotine dependence (chi(2) = 5.42, P = 0.020; chi(2) = 7.58, P = 0.005).
      Furthermore, the T-G (3.9%) haplotype of rs1044396-rs1044397 showed significant
      association with smoking initiation (chi(2) = 6.30, P = 0.012) and the C-G
      haplotype (58.9%) remained positive association with nicotine dependence (chi(2)
      = 8.64, P = 0.003) after Bonferroni correction. The C-G haplotype also
      significantly increased the HSI (P = 0.002) and FTND scores (P = 0.001) after
      Bonferroni correction. CONCLUSION: These findings suggest that CHRNA4 may be
      associated with smoking initiation and the C-G haplotype of rs1044396-rs1044397
      might increase the vulnerability to nicotine dependence in Chinese male smokers.

PMID- 21740769
TI  - Spatial structure of rodent populations and infection patterns of hantavirus in
      seven villages of Shandong Province from February 2006 to January 2007.
AB  - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is endemic in Junan
      county, Shandong Province, China. We conducted geographic information system
      (GIS)-based spatial analysis with the objective of estimating the spatial
      distribution of rodent populations and their hantavirus infection patterns, to
      describe the spatial relationships of hantavirus strains in small ecological
      areas and to identify key areas in endemic areas of HFRS for future public health
      planning and resource allocation. METHODS: Rodent sampling was conducted in seven
      villages in Junan county from February 2006 to January 2007 using field
      epidemiological surveillance. Dynamics of hantavirus infection and population
      densities in rodents were investigated. Spatial statistical techniques including
      Ripley' L index and nearest neighbour hierarchical (NNH) clustering analysis were
      conducted to reveal the spatial structure of rodent populations in seven
      villages. Phylogenetic analysis and two-dimensional minimal spanning tree (2-D
      MST) models were employed to describe the spatial relationship of hantavirus
      strains. RESULTS: Data showed that Mus musculus was the most common species in
      our study area, followed by Rattus norvegicus. Ripley's L index and NNH analysis
      showed that the spatial distribution of all captured rodents, Mus musculus and
      Rattus norvegicus in seven villages were clustered and there were hotspot areas
      of rodent distribution. The branches of 2-D MSTs had similar topologies to those
      of corresponding phylogenetic trees, and hantavirus strains exhibited obvious
      connective traces in seven villages. CONCLUSIONS: These results contribute to the
      understanding of the spatial distribution of rodent populations and hantavirus
      infection patterns in small areas, and identify priority areas within the
      epidemic areas for the development of a better prevention strategy against
      hemorrhagic fever with renal syndrome in a small ecological area.

PMID- 21740770
TI  - Evaluation of visual functional and morphology change in young patients with
      idiopathic choroidal neovascularization.
AB  - BACKGROUND: Idiopathic choroidal neovascularization (ICNV) is an uncommon
      disorder affecting primarily individuals younger than the age of 50 years. In CNV
      patients, no apparent cause can be determined. This study aimed to evaluate the
      functional and morphological change of the retina with ICNV in young adults.
      METHODS: In this retrospective study, 32 eyes of 32 patients with subfoveal or
      juxta/extra foveal ICNV had been admitted into the Shanghai First People's
      Hospital from January 2009 to July 2010. The functional changes were evaluated
      using the best corrected visual acuity (BCVA) and the microperimetry in the
      macular area. The morphology changes were evaluated using optical coherence
      tomography (OCT), the color fundus photography and the fluorescein angiography.
      RESULTS: Seventeen patients with juxta/extra foveal and 15 subfoveal CNV were
      investigated. The mean logarithm of the minimum angle of resolution (LogMAR) BCVA
      was 0.39, the mean central retinal thickness (CRT) was 334 um, and the mean
      sensitivity (MS) was 11.8 decibels (dB). In the subfoveal group, there was a
      strong correlation between CRT and BCVA (r = -0.675, F = 2.167, P < 0.01); as
      well as that between CRT and MS (r = -0.681, F = 22.91, P < 0.01). While in the
      juxta/extra foveal CNV group, the correlation of CRT and BCVA was not significant
      (r = -0.071, F = 1.018, P > 0.05); neither was the correlation of CRT and MS (r =
      -0.142, F = 36.54, P > 0.05). The microperimetry (MP-1) test revealed 17 (53%)
      patients with stable fixation, 9 (28%) with relatively unstable and 6 (19%) with
      unstable fixation. Fixation stability correlated positively with sensitivity in
      the central 2 degrees  diameter area (r = 0.380, F = 3.213, P < 0.05) and the
      duration of symptoms (r = 0.401, F = 7.933, P < 0.05). CONCLUSIONS: ICNV was
      associated with reduced total MS, unstable fixation and eccentric fixation. These
      findings emphasized functional change in ICNV is beyond the BCVA and regular
      morphology change, which provided additional information of functional evaluation
      in clinical practice.

PMID- 21740771
TI  - Analysis on hidden blood loss of total knee arthroplasty in treating knee
      osteoarthritis.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is an important therapy for the
      treatment of various late-stage knee diseases. However, it has been observed that
      patients have lower hemoglobin (HB) counts postoperatively, which are
      significantly inconsistent with the measured blood loss. Although the concept of
      hidden blood loss has been presented in 2000, very little clinical attention has
      been paid since then. In this study, we investigated the characteristics and
      influential factor of hidden blood loss after TKA in treating knee
      osteoarthritis. METHODS: One hundred and eight patients, with 42 males and 66
      females, were retrospectively analyzed. The perioperative blood loss and the
      hidden blood loss following TKA were calculated by Gross formula. Potential
      factors affecting perioperative and hidden blood loss included gender, surgical
      time, tourniquet time, hemostasis (during operation with deflating tourniquet),
      and reinfusion of salvaged blood. RESULTS: The average perioperative blood loss
      was found to be (1553 +/- 356) ml and the average hidden blood loss was (793 +/-
      223) ml. The hidden blood loss of the male was significantly higher than that of
      the female, and was reduced by hemostasis during the operation with a deflating
      tourniquet. Hidden blood loss was not affected by postoperative blood salvage and
      reinfusion, surgical time, or tourniquet time. CONCLUSIONS: When calculating the
      value of hidden blood loss by Gross formula, the lowest value of hematocrit
      should be chosen as the parameter so that hidden blood loss would not be
      underestimated. No significant differences could be found in hidden blood loss
      for males compared to females. Hidden blood loss can be reduced by hemostasis
      during operation with a deflating tourniquet. Although reinfusion of salvaged
      blood could not reduce the perioperative blood loss or hidden blood loss, it was
      still an effective method to reduce transfusion rate.

PMID- 21740772
TI  - Comparision of high sensitivity C-reactive protein and matrix metalloproteinase 9
      in patients with unstable angina between with and without significant coronary
      artery plaques.
AB  - BACKGROUND: Inflammation within vulnerable coronary plaques may cause unstable
      angina by promoting rupture and erosion. C-reactive protein (CRP) is the most
      reliable and accessible test method for clinical use for identifying coronary
      artery disease event. Matrix metalloproteinase 9 (MMP-9) is highly over-expressed
      in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels
      of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as
      well as in those with unstable angina without coronary plaques. METHODS: Patients
      with newly diagnosed unstable angina pectoris from clinical presentation and ECG,
      who were undergoing coronary angiography from April 2007 to April 2009, were
      included in this study. A total of 170 subjects were enrolled in the study.
      Before angiography, the baseline clinical data (mainly including conventional
      risk factors) was collected. These patients were divided into two groups, a non
      plaque group (G1) which included 55 patients with no significant stenosis or less
      than 20% stenosis in at least one of the major coronary artery branches, and a
      plaque group (G2) which included 115 patients with at least one of the major
      coronary artery branches unstable angina pectoris with at least 50% stenosis of
      one major coronary artery. The patients presenting with calcified nodules of a
      major coronary artery were excluded from this study. We examined the serum levels
      of MMP-9 for all cases by multi-effect enzyme-linked immunosorbent assay.
      RESULTS: There was a significant difference in the serum levels of MMP-9 between
      the two groups (P < 0.001). The percentage of patients with hypertension,
      diabetes and current smokers were significantly different between the two groups
      (P = 0.034, P = 0.031, and P = 0.044 respectively). The univariate Logistic
      regression analyses of risk factors showed that smoking was the main risk factor
      for angina in the non-plaque group with the OR being 1.95 (95%CI 1.02 - 3.75).
      Hypertension, diabetes mellitus were negatively related with the occurrence of
      angina in the non-plaque group with the ORs being 0.50, and 0.36, respectively
      (95%CI 0.26 - 0.96 and 0.14 - 0.94). The MMP-9 level was negatively related to
      the occurrence of angina in the non-plaque group with an OR of 0.59 (95%CI 0.47 -
      0.81). CONCLUSIONS: There is a significantly difference in MMP-9 levels between
      the plaque and non-plaque groups. Current smoking has a significant influence on
      unstable angina patients without documented plaques. The serum MMP-9 level may be
      a significant biomarker which can help differentiate patients with unstable
      angina with plaques from those with unstable angina but without plaques.

PMID- 21740773
TI  - Sixty-two severe and critical patients with 2009 influenza A (H1N1) in Shanghai,
      China.
AB  - BACKGROUND: Pandemic influenza A (H1N1) emerged rapidly in China in May 2009.
      Preliminary comparisons with seasonal influenza suggest that pandemic 2009
      influenza A (H1N1) disproportionately affects younger ages and causes generally
      mild disease. To characterize disease progress, comorbidities, and treatment
      outcomes among consecutive severe and critically ill patients in a hospital
      served as a reference center for the care of patients with H1N1 in Shanghai,
      China. METHODS: A retrospective study on 62 severe and critically ill patients
      with 2009 influenza A (H1N1) was conducted in Shanghai Public Health Clinical
      Center. Demographic data, symptoms, comorbidities, disease progression,
      treatments, and clinical outcomes were collected for analysis. RESULTS: Sixty-two
      severe or critically ill patients were admitted to the hospital with confirmed
      2009 influenza A (H1N1) infection. The median age of the study cohort was 40
      years old with a range from 18 years to 75 years, and 67.7% were males. All
      patients presented with fever and respiratory symptoms. At presentation, 34
      patients (54.8%) had comorbidities such as smoking (29.0%), hypertension (29.0%)
      and hepatitis B virus infection (9.7%). The median time from symptom onset to
      hospital admission was 6 days (interquartile-range 3 - 14 days) and 23 critically
      ill patients were admitted to Intensive Care Unit after admission. All the
      patients received neuraminidase inhibitors (oseltaminir), while 60 patients
      (96.7%) were treated with antibiotics, and 39 (62.9%) with corticosteroids.
      Twenty-three critical cases received noninvasive mechanical ventilation on the
      first day of admission, and 3 of them ultimately required invasive ventilation.
      Four death reports (6.5%) were filed within the first 14 days from the onset of
      critical illness with the primary causes of severe acute respiratory distress
      syndrome, hypoxemia, or complications, secondary infection and sepsis,
      pyopneumothorax and stroke. CONCLUSIONS: Severe illness from 2009 influenza A
      (H1N1) infection in Shanghai occurred among young individuals. Critical cases
      were associated with severe hypoxemia, multisystem organ failure, and a
      requirement for mechanical ventilation. Most patients had a good prognosis.

PMID- 21740774
TI  - Dosimetric comparison between helical tomotherapy and intensity-modulated
      radiation therapy plans for non-small cell lung cancer.
AB  - BACKGROUND: Helical tomotherapy (HT) is a new image-guided intensity-modulated
      radiation therapy (IMRT) technique. It is reported that HT plan for non-small
      cell lung cancer (NSCLC) can give better dose uniformity, dose gradients, and
      protection for the lung than IMRT plan. We compared the dosimetric
      characteristics of HT for NSCLC with those of conventional IMRT to observe the
      superiority of HT. METHODS: There was a comparative case series comprising 10
      patients with NSCLC. Computed tomographic (CT) images of delineated targets were
      transferred to the PrecisePlan planning system (IMRT) and Tomo planning system
      (HT). The prescription doses were 70 Gy/33F for the gross tumor volume (GTV) and
      the visible lymph nodes (GTVnd), and 60 Gy/33F for the clinical target volume
      (CTV) and the clinical target volume of the visible lymph nodes (CTVnd). The dose
      restrictions for organs at risk were as follows: the maximum dose to spinal cord
      <= 45 Gy, V20 to the total lungs < 30%, V50 to the heart < 50%, and V55 to the
      esophagus < 50%. Both plans were evaluated by means of the dose coverage of the
      targets, dose-volume histograms (DVHs), and other dosimetric indices. RESULTS:
      The dose coverage, conformity, and homogeneity of the targets' volumes were found
      to be satisfactory in both plans, but the homogeneity of the HT plan was better
      than that of IMRT. The high-dose radiation volume (V20-V30) to the lung and the
      mean lung dose (MLD) decreased (P < 0.05), but the low-dose radiation volume (V5
      V10) increased slightly in the HT plan (P > 0.05). The maximum doses to the
      spinal cord, heart, esophagus and trachea in the HT plan were lower than those in
      the IMRT plan, but the differences were not statistically significant.
      CONCLUSIONS: The HT plan provids better dose uniformity, dose gradients, and
      protection for the organs at risk. It can reduce the high-dose radiation volume
      for lung and the MLD, but may deliver a larger lung volume of low-dose radiation.

PMID- 21740775
TI  - Prognostic value of echocardiographic right/left ventricular end-diastolic
      diameter ratio in idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: An echocardiographic right/left ventricular end-diastolic diameter
      ratio (RV/LV ratio) >= 0.9 is an independent predictor of poor prognosis in
      patients with acute pulmonary embolism. Right ventricular dilation is a common
      characteristic of both acute pulmonary embolism and idiopathic pulmonary arterial
      hypertension (IPAH). However, the prognostic value of the RV/LV ratio in patients
      with IPAH is unknown. METHODS: Ninety-five consecutive patients with newly
      diagnosed IPAH were included, 17 were re-evaluated by echocardiography after 3 -
      12 months of targeted therapy. Follow-up data were obtained by telephone
      interviews and review of the patients' records. RESULTS: Higher RV/LV ratios were
      associated with greater functional impairment. The RV/LV ratio was positively
      correlated with pulmonary vascular resistance (r = 0.549, P < 0.001) and plasma N
      terminal pro-brain natriuretic peptide level (r = 0.575, P < 0.001), but
      negatively correlated with cardiac output (r = -0.517, P < 0.001) and mixed
      venous oxygen saturation (r = -0.599, P < 0.001). Twenty-seven patients died
      during follow-up period. Sensitivity and specificity of an RV/LV ratio >= 0.84
      for predicting death were 85.2% and 51.5%, respectively. The RV/LV ratio and body
      mass index were independent predictors of death by multivariate Cox analysis (P <
      0.01). A baseline RV/LV ratio >= 0.84 or a further increase in the RV/LV ratio
      during targeted therapy indicated a poor prognosis (P < 0.01). CONCLUSION: The
      RV/LV ratio helps to assess the severity of IPAH and may serve as an independent
      predictor of prognosis in patients with IPAH.

PMID- 21740776
TI  - Drug synergistic antifertility effect of combined administration of low-dose
      gossypol with steroid hormones in rats.
AB  - BACKGROUND: Our previous studies suggested that low-dose gossypol combined with
      steroid hormones has a reversible antifertility role in adult male rats, and the
      course of treatment was shorter than that of either gossypol or steroid hormones
      alone. This result suggested that low-dose gossypol and steroid hormones have a
      drug synergistic effect on antifertility. The aim of the study was to find the
      target organs of the antifertility synergistic effect of the combined regimen.
      METHODS: Thirty-two adult male rats were divided into four groups randomly: group
      GH, rats were fed orally with gossypol acetic acid (GA, 12.5 mg*kg(-1)*d(-1)) and
      desogestrel (DSG, 0.125 mg*kg(-1)*d(-1))/ethinylestradiol (EE, 0.025 mg*kg(-1)*d(
      1))/testosterone undecanoate (TU, 100 mg*kg(-1)*d(-1)); group G, a single dose of
      GA (12.5 mg*kg(-1)*d(-1)) was given; group H, the same dosage of DSG/EE/TU as in
      group GH were administered; group C, rats were treated with vehicle (1% methyl
      cellulose) as control. Testes and epididymis were removed at 8 weeks post
      treatment for evaluating their weight, volumes, volume fraction, and total volume
      of testicular tissue structures and the seminiferous tubule diameter using
      stereological assay. Sperm cell numbers and the motility of epididymal sperm were
      quantitated by flow cytometry and morphological methods. RESULTS: Compared with
      group C, spermatogenesis was normal in group G and suppressed in groups H and GH.
      Similar changes of testicular tissue structures and sperm number were found in
      groups H and GH. The decreases of epididymal sperm number and motility in group
      GH were greater than that of the low-dose gossypol or steroid hormones alone
      group. CONCLUSIONS: The suppression of spermatogenesis was induced by steroid
      hormones in the combined regimen, and the epididymis was the target organ of low
      dose gossypol. Combined use of low-dose gossypol and steroid hormones played a
      comprehensive antifertility role in their synergistic effect on reducing the
      number and motility of epididymal sperm.

PMID- 21740777
TI  - Remote postconditioning induced by brief pulmonary ischemia and reperfusion
      attenuates myocardial reperfusion injury in rabbits.
AB  - BACKGROUND: The lung is one of the most important organs that are sensitive to
      ischemia. We hypothesized that remote postconditioning (RPostC) induced by brief
      occlusion and reperfusion of the pulmonary artery could attenuate myocardial
      reperfusion injury. METHODS: Thirty rabbits were randomized into three groups.
      Group ischemia-reperfusion (IR) (n = 10) were anesthetized rabbits subjected to
      30-minute occlusion of the left anterior descending coronary artery followed by
      180-minute reperfusion. Group RPostC (n = 10) had the left pulmonary artery
      blocked for five minutes followed by a 5-minute reperfusion, and the left
      anterior descending coronary artery (LAD) occluded for 30 minutes with a 180
      minute reperfusion. Group L-N(w)-nitro-L-arginine methylester (L-NAME) + RPostC
      (n = 10) had the left pulmonary artery blocked for five minutes followed by a 5
      minute reperfusion and intravenous infusion of L-NAME (10 mg/kg), and the LAD
      occluded for 30 minutes with a 180-minute reperfusion. Blood samples were taken
      for levels of creatine kinase (CK), superoxide dismutase (SOD) and
      malondialdehyde (MDA) at three different time points. At the end of the
      experiment, tissue samples of the infarcted region were harvested to calculate
      the cardiomyocyte apoptosis index (AI) by TUNEL. A piece of left and right lung
      tissue was harvested to evaluate the damage to the lung. RESULTS: After
      reperfusion for 180 minutes, the concentration of CK was lower in group RPostC,
      (4.79 +/- 0.27) U/ml, than that in group IR, (6.23 +/- 0.55) U/ml (P < 0.01), and
      group L-NAME + RPsotC, (5.86 +/- 0.42) U/ml (P < 0.01). The concentration of MDA
      was lower in group RPostC, (6.06 +/- 0.36) nmol/ml, than that in group IR, (11.41
      +/- 0.91) nmol/ml (P < 0.01), and group L-NAME + RPostC, (11.06 +/- 0.62) nmol/ml
      (P < 0.01). The activity of SOD was higher in group RPostC, (242.34 +/- 25.02)
      U/ml, than that in group IR, (148.05 +/- 18.24) U/ml (P < 0.01), and group L-NAME
      + RPostC, (160.66 +/- 9.55) U/ml (P < 0.01). The apoptosis index was lower in
      group RPostC, (14.25 +/- 5.20)%, than that in group IR, (35.77 +/- 10.09)% (P <
      0.01), and group L-NAME + RPostC, (30.37 +/- 7.76)% (P < 0.01). No significant
      difference caused by pulmonary ischemia was found in the lung tissue among the
      three groups. CONCLUSIONS: RPostC may attenuate myocardial ischemia-reperfusion
      injury connected to the activity of endothelial nitric oxide synthase. Brief
      pulmonary ischemia may not be harmful to lungs.

PMID- 21740778
TI  - Definition of an acronym.

PMID- 21740779
TI  - Assessing validation of dual fluoroscopic image matching method for measurement
      of in vivo spine kinematics.
AB  - BACKGROUND: Accurate knowledge of the spinal structural functions is critical to
      understand the biomechanical factors that affect spinal pathology. Many studies
      have investigated the human vertebral motion both in vitro and in vivo. However,
      determination of in vivo motion of the vertebrae under physiologic loading
      conditions remains a challenge in biomedical engineering because of the
      limitations of current technology and the complicated anatomy of the spine.
      METHODS: For in vitro validation, a human lumbar specimen was imbedded with steel
      beads and moved to a known distance by an universal testing machine (UTM). The
      dual fluoroscopic system was used to capture the spine motion and reproduce the
      moving distance. For in vivo validation, a living subject moved the spine in
      various positions while bearing weight. The fluoroscopes were used to reproduce
      the in vivo spine positions 5 times. The standard deviations in translation and
      orientation of the five measurements were used to evaluate the repeatability of
      technique. The accuracy of vertebral outline matching with metallic marks
      matching technology was compared. RESULTS: The translation positions of the human
      lumbar specimen could be determined with a mean accuracy less than 0.35 mm and a
      mean repeatability 0.36 mm for the image matching technique. The repeatability of
      the method in reproducing in vivo human spine six degrees of freedom (6DOF)
      kinematics was less than 0.43 mm in translation and less than 0.65 degrees  in
      rotation. The accuracy of metallic marks and vertebral outline matching did not
      show significant difference. CONCLUSIONS: Combining a dual fluoroscopic and
      computerized tomography imaging technique was accurate and reproduceable for
      noninvasive measurement of spine vertebral motion. The vertebral outline matching
      technique could be a useful technique for matching of vertebral positions and
      orientations which can evaluate and improve the efficacy of the various surgical
      treatments.

PMID- 21740780
TI  - Resveratrol induces apoptosis in pancreatic cancer cells.
AB  - BACKGROUND: Pancreatic cancer is one of the most lethal human cancers with a very
      low survival rate of 5 years. Conventional cancer treatments including surgery,
      radiation, chemotherapy or combinations of these show little effect on this
      disease. Several proteins have been proved critical to the development and the
      progression of pancreatic cancer. The aim of this study was to investigate the
      effect of resveratrol on apoptosis in pancreatic cancer cells. METHODS: Several
      pancreatic cancer cell lines were screened by resveratrol, and its toxicity was
      tested by normal pancreatic cells. Western blotting was then performed to analyze
      the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer
      cell lines. RESULTS: In the screened pancreatic cancer cell lines, capan-2 and
      colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol
      exhibited insignificant toxicity to normal pancreatic cells. In resveratrol
      sensitive cells, capan-2 and colo357, the activation of caspase-3 was detected
      and showed significant caspase-3 activation upon resveratrol treatment; p53 and
      p21 were also detected up-regulated upon resveratrol treatment. CONCLUSION:
      Resveratrol provides a promising anti-tumor strategy to fight against pancreatic
      cancer.

PMID- 21740781
TI  - Primary stromal cells isolated from human various histological/pathological
      prostate have different phenotypes and tumor promotion role.
AB  - BACKGROUND: Prostate stromal cells are known to regulate epithelial growth as
      well as support and maintain epithelial function. However, how stromal cells
      regulate epithelial cells and what differences among various
      histological/pathological prostate stromal cells in prostate cancer progression
      still remain unclear. This study aimed to investigate the different phenotypes of
      human various histological/pathological prostate stromal cells, and their role in
      tumor promotion. METHODS: The different phenotypes of the human normal prostatic
      peripheral zonal primary stromal cells (NPPF), transitional zonal primary stromal
      cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were
      examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC)
      assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF,
      and CAF were examined with MTT assay and Annexin V-FITC assay. The gene
      expression of different histological/pathological prostate stromal cells was
      profiled by microarray and hierarchical cluster analysis. RESULTS: The growth
      rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis.
      In vitro stromal-C4-2B cell line co-culture models, the proliferation and
      apoptosis of C4-2B cell line were differently affected by human various
      histological/pathological prostate stromal cells. CAF showed the most powerful
      effect to C4-2B cell line, as opposed to a weakest effect of NPTF. Microarray and
      hierarchical cluster analysis showed that the differentially expressed genes of
      CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent
      with clinical observations that prostate cancer mostly derived from the
      peripheral zone and does not usually occur in the transitional zone. CONCLUSION:
      NPPF, NPTF and CAF possess extremely different biological characteristics and
      gene expression, which may play an important role in genesis and development of
      prostate cancer.

PMID- 21740782
TI  - Effect of curettage and copper wire on rabbit endometrium: a novel rabbit model
      of endometrial mechanical injury.
AB  - BACKGROUND: It remains almost a helpless situation for the recurrent implantation
      failure and pregnancy loss caused by endometrial injury at present. The purpose
      of this study was to develop a rabbit model of endometrial mechanical injury that
      could provide a research platform for this difficult clinical predicament.
      METHODS: Three experiments were conducted. Experiment 1: Curettages in both
      uterus horns and copper wire inserting after curettage (double-injury) in one
      horn. The histological changes were monitored at 0, 24, 48, 72 hours, as well as
      in 1 and 2 weeks after operation. Experiment 2: Direct copper wire inserting in
      one horn and double-injury in other horn. The wires in both horns were removed
      after 2 weeks. The histological changes were recorded at 0, 1 and 2 weeks after
      wire removal. Experiment 3: Double-injury procedure in one horn was performed and
      wire was removed after 2 weeks; another horn was remained normal to serve as
      control. Histological changes were recorded, tissue areas were measured, and
      proliferation indices (PIs, %) were calculated at 1, 2, 4 and 8 weeks after wire
      removal, respectively. RESULTS: The experiments revealed that the injured
      endometrium by simple curettage or copper wire could be fully repaired. While the
      endometrial regeneration was severely impaired by double-injury, both areas of
      endometrium and uterine cavity decreased (P < 0.05); both PIs of glandular
      epithelial and stromal cells increased and reached maximum at 4 weeks (P < 0.05),
      but returned by 8 weeks. CONCLUSION: This study demonstrated that a rabbit model
      of endometrial injury could be effectively established through a double-injury
      procedure of curettage and copper wire with comparable clinical index.

PMID- 21740783
TI  - Epicardial isolation of pulmonary veins with ethanol in open chest dogs.
AB  - BACKGROUND: Radiofrequency (RF) ablation has become a widely accepted treatment
      for atrial fibrillation (AF). This study aimed to identify the efficacy and
      safety of pulmonary vein (PV) ablation with ethanol and to explore an alternative
      energy source for catheter ablation of AF. METHODS: Twelve open-chest mongrel
      dogs were randomized into ethanol ablation group and control group. Both the
      injections and electrophysiological mapping procedures were performed
      epicardialy. In ethanol ablation group (n = 6), injections were performed to
      circumferentially ablate the root of each PV (0.2 ml each site, 3 mm apart) with
      95% ethanol using an 1 ml injector. In control group (n = 6), saline was injected
      other than ethanol. PV isolation was confirmed with a circular catheter
      immediately after the procedure and at follow up of 30 days. PV isolation was
      defined as the absence of PV potentials at each electrode of the circular
      catheter positioned at the PV side of the lesions, as well as complete conduction
      block into left atrium (LA) during PV pacing. RESULTS: PV electrical isolation
      with complete bidirectional conduction block was achieved with ethanol
      immediately and at 30 days in 95% of PVs, while saline injection caused only
      transient conduction changes between LA and PVs. In ethanol group, histologic
      analysis showed transmural lesions at 30 days. And there was no evidence of PV
      stenosis or thrombus formation. Mean LA diameter was not significantly different
      between baseline and 30 days. CONCLUSION: Ethanol is a safe energy source to
      effectively isolate PV in canine model and may be promising in endocardial
      ablation procedure of AF patients in the future.

PMID- 21740784
TI  - A case of multiple system atrophy: onset with the cold hands sign.

PMID- 21740785
TI  - Pancreatic and peri-pancreatic lesions mimic pancreatic islet cell tumor in
      multidetector computed tomography.
AB  - OBJECTIVE: This pictorial review aimed to summarize the most possible
      differential diagnosis of pancreatic islet cell tumor (PICT). DATA SOURCES: Data
      used in this review were mainly from Medline and Pubmed in English. And all
      clinical images in this review were from Department of Radiology, Peking Union
      Medical College Hospital, Beijing, China. STUDY SELECTION: Cases of pancreatic
      cystadenoma, solid pseudo-papillary tumor of the pancreas, pancreatic metastasis,
      pancreatic adenocarcinoma, para-pancreatic neuroendocrine tumors, Castleman
      disease, gastrointestinal stromal tumor, splenic artery aneurysm and accessory
      spleen were selected in this pictorial review for differential diagnosis of PICT.
      RESULTS: Careful analysis of imaging features and correlation with the clinical
      manifestations may allow a more specific diagnosis. It is also important that the
      radiologist is familiar with the anatomic variants and disease entities which
      mimic pancreatic islet cell tumor in order to avoid an improper treatment
      protocol. CONCLUSIONS: Many congenital anatomic variants or other pancreatic and
      peri-pancreatic diseases may mimic MDCT appearance of pancreatic islet cell
      tumor. Radiological, clinical and pathological characteristics should be
      considered for the final diagnosis.

PMID- 21740786
TI  - Preliminary characterization of acute aortic dissection in the mainland of China.
AB  - OBJECTIVE: To explore the differences in the characteristics of acute aortic
      dissection (AAD) among less and more economically developed countries with
      various cultures and races. DATA SOURCES: Reports from the International Registry
      of Acute Aortic Dissection (IRAD) and the mainland of China (MC) were collected
      by searching the PubMed Database and the Chinese Journal Full-text Database from
      January 2000 to March 2009. STUDY SELECTION: Those reports from IRAD and MC
      containing larger numbers of cases and complete patients' information were
      selected, which focused on concrete issues of diagnosing or managing AAD were
      excluded if they were not able to reflect the overall characteristics of this
      condition. And the data from the article containing the largest number patients
      reported by the same medical center in MC were taken into statistics. RESULTS:
      AAD patients from MC were significantly younger than IRAD countries and the
      percentage of male patients in the Chinese group was higher than IRAD countries
      (80.7% vs. 68.6%, P < 0.001). Patients in MC were less likely to present with
      typical symptoms and signs except for any focal neurological deficits. Different
      from the IRAD group, Chinese patients were prone to undergo magnetic resonance
      imaging (MRI) to make the diagnosis of AAD (45.5% vs. 11.6%, P < 0.001). The in
      hospital mortality was similar between 2 groups but only smaller proportion of
      AAD patients in MC underwent surgical or medical treatment. CONCLUSIONS: The
      general characteristics of AAD patients in MC were shown and differences in some
      clinical variables between MC and IRAD groups still existed.

PMID- 21740787
TI  - Effect of polymorphism and type II diabetes on aspirin resistance in patients
      with unstable coronary artery disease.
AB  - BACKGROUND: Aspirin is widely used in the secondary prevention of coronary artery
      diseases, including myocardial infarction, stroke, and vascular related deaths.
      However, the antiplatelet effect of aspirin appears to be variable and aspirin
      resistance (AR) is currently still controversial for Chinese patients. The aim of
      this study was to describe the prevalence of AR, and identify possible risk
      factors associated with a lack of response to aspirin treatments in patients with
      unstable coronary artery disease. METHODS: Platelet function tests with
      arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2)
      concentrations were performed in 262 patients with unstable coronary artery
      disease who had not been taking aspirin before admission. ARA induced platelet
      aggregation and 11-DH-TXB2 were detected to evaluate the functional and
      biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin
      administration. Six-month follow-up was completed in patients who developed AR to
      evaluate the effect of aspirin in a long-term treatment. GP1Balpha (C1018T), Pl
      (A1/A2), P2Y1 (A1622G), TBXA2R (T924C) were also detected to evaluate the
      influence of genetic variant on aspirin responsiveness. RESULTS: A total of 8.8%
      of patients were indentified as AR at the first day after aspirin treatment. The
      level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P
      < 0.05). There was no relationship between ARA induced platelet aggregation and
      urinary 11-DH-TXB2 levels (r = 0.038, P = 0.412). The results of DNA sequencing
      showed that TBXA2R-924TT homozygotes had a significantly high rate of AR.
      Logistic regression demonstrated that diabetes was an independent risk factor of
      AR. CONCLUSIONS: In the beginning period of administration, aspirin was not a
      sufficient factor that inhibits platelet aggregation. TBXA2R-924T allele was
      involved in AR. Diabetes was an independent risk factor of AR.

PMID- 21740788
TI  - Gait instability in patients with small acoustic neuroma.
AB  - BACKGROUND: Small acoustic neuromas seldom result in typical vestibular symptoms,
      despite the tumor arising from the vestibular nerve. In this study, we have shown
      that abnormal gait in eleven patients with small acoustic neuroma could be
      detected in gait analysis by the use of tactile sensor. Patients displayed no
      oculomotor abnormality and had tumors less than 10 mm from the porus acoustics.
      METHODS: Gait related parameters including the coefficients of variations (CV) of
      stance, swing, double support, area ratio of trajectories of center of force
      (TCOF), in addition to the foot pressure difference between both feet, were used
      for assessment of gait. RESULTS: The CV of swing and the area ratio of TCOF were
      greater in patients than those in the control group (P < 0.05). The values of
      these two parameters became greater under an eyes closed condition compared to
      eyes open (P < 0.05) in the patient group. CONCLUSION: These results indicate
      that gait analysis may be helpful to assess vestibulospinal function of patients
      with small acoustic neuroma, the slight vestibular deficits of which can not be
      detected by visual observation.

PMID- 21740789
TI  - Analysis of Chinese women with primary ovarian insufficiency by high resolution
      array-comparative genomic hybridization.
AB  - BACKGROUND: Primary ovarian insufficiency (POI) is defined as a primary ovarian
      defect characterized by absent menarche (primary amenorrhea) or premature
      depletion of ovarian follicles before the age of 40 years. The etiology of
      primary ovarian insufficiency in human female patients is still unclear. The
      purpose of this study is to investigate the potential genetic causes in primary
      amenorrhea patients by high resolution array based comparative genomic
      hybridization (array-CGH) analysis. METHODS: Following the standard karyotyping
      analysis, genomic DNA from whole blood of 15 primary amenorrhea patients and 15
      normal control women was hybridized with Affymetrix cytogenetic 2.7M arrays
      following the standard protocol. Copy number variations identified by array-CGH
      were confirmed by real time polymerase chain reaction. RESULTS: All the 30
      samples were negative by conventional karyotyping analysis. Microdeletions on
      chromosome 17q21.31-q21.32 with approximately 1.3 Mb were identified in four
      patients by high resolution array-CGH analysis. This included the female
      reproductive secretory pathway related factor N-ethylmaleimide-sensitive factor
      (NSF) gene. CONCLUSIONS: The results of the present study suggest that there may
      be critical regions regulating primary ovarian insufficiency in women with a
      17q21.31-q21.32 microdeletion. This effect might be due to the loss of function
      of the NSF gene/genes within the deleted region or to effects on contiguous
      genes.

PMID- 21740790
TI  - Comorbid presentation of severe novel influenza A (H1N1) and Evans syndrome: a
      case report.
AB  - One 22-month-old boy who was admitted for a fever lasting 6 days as well as a
      cough and wheezing lasting 2 days was reported. He was diagnosed with influenza A
      (H1N1, severe type), severe pneumonia, acute respiratory distress syndrome
      (ARDS), Evans syndrome and multiple organ failure. This is the first case of
      novel influenza A (H1N1) and Evans syndrome. The pathogenesis is still unknown.

PMID- 21740791
TI  - A case of mimicking angioedema: chin silicone granulomatous reaction spreading
      all over the face after receiving liquid silicone injection forty years
      previously.
AB  - Liquid injectable silicone has been used for soft tissue augmentation for five
      decades. Many complications following liquid silicone injection have been
      reported. To diagnose and manage silicone granuloma remains difficult. Silicone
      granuloma must be diagnosed with the history of liquid silicone injection and the
      histology of tissue biopsy. We presented a case of granulomatous reaction after
      the injection of liquid silicone for chin augmentation forty years ago, causing
      total facial swelling, which mimicking angioedema initially. We administered
      methylprednisolone to the patient. Initial response to methylprednisolone was
      favorable.

PMID- 21740792
TI  - Laparoscopic partial splenectomy for large splenic epidermoid cyst.
AB  - Splenic epidermoid cysts are relatively rare lesions traditionally treated by
      splenectomy. Concerns about overwhelming postsplenectomy sepsis have led to the
      development of splenic preservation procedures in the treatment of cystic
      diseases of the spleen. Better understanding of the splenic segmental anatomy and
      advances in laparoscopic skills has made laparoscopic partial splenectomy a
      preferred treatment for splenic cysts while preserving splenic function. We
      reported a case of a 30-year-old male patient with a large epidermoid splenic
      cyst managed successfully by laparoscopic partial splenectomy. The patient
      recovered well after operation and was asymptomatic on a follow-up of 1 year with
      no recurrence on ultrasonography and a normal platelet count. Laparoscopic
      partial cystectomy is an acceptable procedure for the treatment of splenic cysts
      which locate in the pole of spleen. On the one hand, it cures the disease
      preserving the splenic tissue without risk of bleeding or recurrence; on the
      other hand, this minimally invasive technique induces a reduced hospital stay and
      a more rapid recovery.

PMID- 21740793
TI  - Mid-ventricular obstructive hypertrophic cardiomyopathy with apical aneurysm and
      sustained ventricular tachycardia: a case report and literature review.
AB  - The case is a 54-year-old man with hypertrophic cardiomyopathy, mid-ventricular
      obstruction, apical aneurysm, and recurrence sustained monomorphic ventricular
      tachycardia (VT). A coronary angiogram revealed myocardial bridging located in
      the middle of the left anterior descending coronary artery (LAD), and the left
      ventriculogram showed an hour-glass appearance of the left ventricular cavity.
      There was a significant pressure gradient of 60 mmHg across the mid-ventricular
      obliteration at rest. A successful myectomy of the inappropriate hypertrophy
      myocardium and excision of the apical aneurysm were performed. Pathologic
      analysis demonstrated fibrosis in the apical aneurysm and thickened and narrowed
      vessels in the adjacent area. During the follow-up of eighteen months, the
      patient remained clinically stable and free from arrhythmic recurrence.

PMID- 21740794
TI  - A 65-year-old man with infratentorial diffuse encephalopathy and hydrocephalus.
AB  - Tuberculous encephalopathy (TBE) is an important diagnosis in countries with a
      high prevalence of tuberculosis. TBE is a life-threatening condition but rarely
      reported in the modern literature. We reported a case of a man with extensive
      parenchymal lesions involving the brainstem and right cerebellar hemisphere that
      resolved after treatment. The clinical, laboratory and pathological features of
      this case are highlighted and the pathogenesis is discussed.

PMID- 21740795
TI  - Association of serum uric acid with different levels of glucose and related
      factors.
AB  - BACKGROUND: Previous studies have demonstrated that serum uric acid (UA) is an
      independent predictor of incident type 2 diabetes mellitus (T2DM) in general
      populations. This study aimed to investigate specific characteristics of UA and
      its relationship between UA and blood glucose and other risk factors in the
      Chinese population. METHODS: A total of 946 subjects were included in this study.
      UA, glucose, insulin, fractional excretion of UA (FEua), creatinine clearance
      rate (Ccr), hemoglobin A1c (HbA1c), fructosamine (FA), blood pressure and lipids
      were studied and also reexamined after the patients underwent two weeks of
      combined therapeutics. RESULTS: UA levels were the highest in subjects with
      impaired glucose regulation (IGR), followed by subjects with normoglycemia (NGT)
      and finally by subjects with T2DM. The level of the 2-hour postprandial insulin
      and the area under the curve for insulin (AUCins) showed a similar tendency. The
      UA levels initially increased with increasing fasting blood glucose (FBG) and
      postprandial blood glucose (PPBG) levels, up to 7 mmol/L and 10 mmol/L,
      respectively, and thereafter decreased at higher FBG and PPBG levels. Compared
      with subjects in the lower serum UA quartile, subjects in the upper quartile of
      serum UA levels had higher weights, triglyceride levels, and creatinine levels as
      well as lower Ccr and FEua levels. Compared with women's group, UA levels were
      higher, and FEua levels were lower in men's group. Sex, body mass index (BMI),
      mean arterial blood pressure (MAP), serum triglycerides (TG), FA and Ccr were
      independent correlation factors of UA. UA decreased and FEua increased after the
      patients underwent a combined treatment. CONCLUSIONS: UA increased initially and
      then decreased as glucose levels increased from NGT to IGR and T2DM. Compared
      with NGT and T2DM, IGR subjects had higher SUA levels, which related to its high
      levels of insulin. Under T2DM, male gender, BMI, MAP, Ccr, TG and FA are
      independent correlation factors of UA. Glucose-lowering, antihypertensive,
      lipemia-regulating combined treatments were of advantage to decline of SUA of
      T2DM.

PMID- 21740796
TI  - Gasless endoscopic surgery through the upper chest in treatment of thyroid tumor.
AB  - BACKGROUND: Recently, there has been a surge of interest in minimally invasive
      techniques with endoscope in thyroid surgery. The aim of this study was to
      investigate the possibility of a scarless neck surgery under endoscopy for the
      treatment of thyroid tumor and to observe the results of this procedure. METHODS:
      A total of 68 patients (64 women and 4 men) underwent the surgery. Their ages
      ranged from 18 to 65 years, with a mean age of (34 +/- 3) years. There were 64
      cases of thyroid adenoma, and 4 cases of nodular goiter. An incision was made on
      the surface of the chest bone. The operation cavity was made by dragging the
      skin. Sixty-four patients underwent partial thyroid lobectomy, four patients
      underwent thyroid lobectomy. RESULTS: All 68 cases showed healing in one stage.
      None of the cases showed paralysis of the recurrent laryngeal nerve or tumor
      recurrence within the next 2 to 60 months of follow-up. The patients experienced
      slight pain after the operation. The patients were satisfied with the cosmetic
      results of the surgery. CONCLUSION: The gasless endoscopic surgery through the
      upper chest, which was performed to treat thyroid tumor, did not leave any scar,
      and was easy to handle, and gave good cosmetic results.

PMID- 21740797
TI  - Is it necessary to stent renal artery stenosis patients before cardiopulmonary
      bypass procedures?
AB  - BACKGROUND: Acute kidney injury (AKI) is associated with poor prognosis after
      cardiopulmonary bypass. The aim of this retrospective study was to investigate
      whether stent implantation before cardiopulmonary bypass has beneficial effect on
      development of AKI in renal artery stenosis (RAS) patients. METHODS: In this
      retrospective study, patients with abnormal baseline serum creatinine (SCr, > 106
      umol/L) were not included. Included patients (n = 69) were divided into two
      groups. Group 1 included 31 RAS patients receiving no stent implantation before
      cardiopulmonary bypass. Group 2 included 38 RAS patients having received stent
      implantation just before cardiopulmonary bypass. To assess AKI after
      cardiopulmonary bypass, serum urea nitrogen, SCr and creatinine clearance were
      recorded at baseline, at the end of operation, during the first and second
      postoperative 24 hours. RESULTS: Baseline characteristics were similar between
      groups. Serum urea nitrogen, SCr, creatinine clearance before and after
      cardiopulmonary bypass were also similar class groups. Incidence of AKI in group
      1 was not significantly different from group 2. In group 1, AKI defined by RIFLE
      between occurred in 7 (22.6%) patients: 5 (16.1%) with RIFLE-R, 2 (6.5%) with
      RIFLE-I, and no patients with RIFLE-F. In group 2, 10 patients (26.3%) had an
      episode of AKI during hospitalization: 6 (15.8%) had RIFLE-R, 4 (10.5%) had RIFLE
      I, and no patients had RIFLE-F. CONCLUSIONS: There are no data suggesting that it
      is necessary to stent RAS patients with normal SCr before cardio-pulmonary
      bypass. However, it cannot be concluded that RAS is not associated with AKI after
      cardiopulmonary bypass.

PMID- 21740798
TI  - Alternatives to albumin administration in hepatocellular carcinoma patients
      undergoing hepatectomy: an open, randomized clinical trial of efficacy and
      safety.
AB  - BACKGROUND: The value of artificial colloids in treating patients with liver
      disease is controversial. The effects of intravascular volume replacement
      regimens on liver function secondary to alteration of the postoperative
      inflammatory response are not known. In this study, we evaluated the effects of
      different volume replacement regimens in hepatocellular carcinoma patients
      undergoing hepatectomy to clarify whether albumin administration can be replaced
      by other volume replacement products. METHODS: Ninety consecutive hepatocellular
      carcinoma patients scheduled for hepatectomy were prospectively randomized to
      receive 20% human albumin (HA), 6% hydroxyethyl starch (HES) or lactated Ringer's
      solution (LR) for postoperative volume replacement. Hemodynamic, liver function
      and inflammatory response parameters were recorded on postoperative days one,
      three, and five throughout the investigation period. RESULTS: Significantly less
      volume was required in the HA and the HES groups. Although patients in all groups
      had similar baseline values, the plasma osmolality was significantly higher in
      the HA and HES groups. Total bilirubin (TB), alanine aminotransferase (ALT), and
      aspartate aminotransferase (AST) increased from baseline in all groups, and did
      not differ significantly between groups. C-reactive protein (CRP) was
      significantly lower in the HES group compared with the other groups. CONCLUSIONS:
      In hepatocellular carcinoma patients undergoing hepatectomy, HA can be replaced
      by HES or LR in well selected patients. Hemodynamic stability, liver function,
      and postoperative clinical outcomes could be equivalently achieved in the HES
      group; also, HES may exert more favorable effects on the acute phase response.

PMID- 21740799
TI  - Distribution of wall shear stress in carotid plaques using magnetic resonance
      imaging and computational fluid dynamics analysis: a preliminary study.
AB  - BACKGROUND: Wall shear stress is an important factor in the destabilization of
      atherosclerotic plaques. The purpose of this study was to assess the distribution
      of wall shear stress in advanced carotid plaques using high resolution magnetic
      resonance imaging and computational fluid dynamics. METHODS: Eight diseased
      internal carotid arteries in seven patients were evaluated. High resolution
      magnetic resonance imaging was used to visualize the plaque structures, and the
      mechanic stress in the plaque was obtained by combining vascular imaging post
      processing with computational fluid dynamics. RESULTS: Wall shear stresses in the
      plaques in all cases were higher than those in control group. Maximal shear
      stresses in the plaques were observed at the top of plaque hills, as well as the
      shoulders of the plaques. Among them, the maximal shear stress in the ruptured
      plaque was observed in the rupture location in three cases and at the shoulder of
      fibrous cap in two cases. The maximal shear stress was also seen at the region of
      calcification, in thrombus region and in the thickest region of plaque in the
      other three cases, respectively. CONCLUSION: Determination of maximal shear
      stress at the plaque may be useful for predicting the rupture location of the
      plaque and may play an important role in assessing plaque vulnerability.

PMID- 21740800
TI  - Clinicopathological and prognostic features of hepatoid adenocarcinoma of the
      stomach.
AB  - BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of
      gastric carcinoma, which has its unique clinicopathological features and poorer
      prognosis than that of the ordinary gastric adenocarcinoma. At present, there is
      still a lack of understanding about this disease. The current study aimed to
      summarize and discuss the clinical, pathological, immunohistochemical, and
      prognostic features of this disease. METHODS: A total of 20 patients of HAS were
      retrospectively studied. All the patients were treated in Cancer Hospital of
      Chinese Academy of Medical Sciences between March 1998 and October 2009.
      Statistical analysis, including the Kaplan-Meier method, log-rank test and Cox
      model, were performed by the SPSS 15.0 software. RESULTS: Seventeen patients
      (85%) had at least 1 lymph node metastases; 17 patients (85%) received
      postoperative immunohistochemical examinations, with an alpha-fetoprotein (AFP)
      positive rate of 94.1% (16/17); 14 patients had distant metastases (including 12
      liver metastases, 1 lung metastasis, and 1 celiac widespread metastases), and one
      simultaneously had anastomotic recurrence and liver metastases. The overall
      survival time was 2 - 99 months (median: 12.0 months). The 3-year survival rate
      of the 20 patients was 17.2%. The 3-year survival rate of patients with complete
      hepatocyte-like regions and those with both hepatocellular carcinoma and
      adenocarcinoma regions was 20.0% and 17.5%, respectively (P = 0.361). The
      survival difference among the radical surgery group, palliative surgery group and
      no surgery group was statistically significant (P = 0.022). The Kaplan-Meier
      method and log-rank test showed that surgery, pTNM stages, and adjuvant
      chemotherapy were associated with prognosis (P < 0.05). The Cox model only
      confirmed that the pTNM stages and adjuvant chemotherapy had statistical
      significance for the prognosis of HAS (P < 0.05) due to the limited cases.
      CONCLUSIONS: HAS is a special type of gastric carcinoma and has a poor prognosis.
      The pTNM stage is an independent risk factor for HAS. Multidisciplinary therapy,
      including surgery and chemotherapy, may improve the prognosis of HAS.

PMID- 21740801
TI  - Preliminary experience using transthoracic echocardiography guiding percutaneous
      closure of ruptured right sinus of Valsalva aneurysm.
AB  - BACKGROUND: In the 21st century, minimally invasive treatment is one of the main
      developmental directions of medical sciences. It is well known that the
      echocardiography plays an important role during interventional treatments of some
      structural heart diseases. Because the ruptured right sinus of the Valsalva
      aneurysm (RRSVA) is a rare disease, there were few reports about percutaneous
      catheter closure of RRSVA. This study aimed to sum up our experience with
      transthoracic echocardiography (TTE) during percutaneous catheter closure of
      RRSVA. METHODS: Five RRSVA cases were treated with percutaneous catheter closure.
      The whole procedure was guided and monitored by TTE and fluoroscopy. The maximum
      diameter of the RRSVA was measured by TTE before and after the catheter passed
      through the rupture site. A duct occluder 2 mm larger than the maximum diameter
      was chosen. The closure effects were evaluated with TTE and fluoroscopy
      immediately after the occluding device was deployed. All patients were followed
      up by TTE for 8 to 30 months. RESULTS: Before the catheter passed through the
      rupture site the maximum diameter of the RRSVA measured with TTE and aortography
      were (7.9 +/- 2.1) mm and (7.8 +/- 1.8) mm. After the catheter passed through the
      rupture site the maximum diameter measured with TTE was (11.2 +/- 3.2) mm, which
      was significantly larger than before the procedure (P < 0.05). The percutaneous
      catheter closure was successful in four cases and failed in one. Compared to the
      aortography the TTE was better at distinguishing residual shunts from aortic
      valve regurgitation immediately after the occluding device was deployed. There
      were no complications during 8 to 30 months of follow-up. CONCLUSION:
      Transthoracic echocardiography can play an important role during percutaneous
      catheter closure of RRSVA, especially for estimating the size of the RRSVA after
      the catheter passes through the rupture site, and differentiating residual shunt
      from aortic valve regurgitation immediately after the occluding device is
      deployed.

PMID- 21740802
TI  - Twist modulates lymphangiogenesis and correlates with lymph node metastasis in
      supraglottic carcinoma.
AB  - BACKGROUND: Twist is a highly conserved epithelial-mesenchymal transcription
      factor that has been reported to be a key factor in tumor malignancy, including
      lymph node metastasis. It represents the major step of dissemination and serves
      as a chief prognostic indicator of disease progression. However, the mechanism by
      which Twist regulates lymph node metastasis remains incompletely understood.
      Studies on the mechanism of metastasis are thus required for determining
      appropriate therapeutic strategies. METHODS: Immunohistochemistry for lymphatic
      vessel endothelial receptor 1 (LYVE-1), Ki-67, Twist, vascular endothelial growth
      factor C (VEGF-C), and vascular endothelial growth factor receptor 3 (VEGFR-3)
      was performed to detect lymphatic vessel density (LVD), cell proliferation levels
      and the expressions of Twist, VEGF-C, and VEGFR-3 were determined from 66 primary
      supraglottic carcinoma tissue samples from 36 patients with lymph node metastasis
      (pathological N+, pN+) and 30 patients without metastasis (pathological N0, pN0).
      Western blotting analysis of the proteins in pN+ and pN0 primary tumors was used
      to characterize the expressions of Twist, VEGF-C, and VEGFR-3 further. RESULTS:
      The LVD was 22.4 +/- 10.3 in pN+ patients and 6.8 +/- 4.1 in pN0 ones. For Ki-67,
      the number of proliferous cells in pN+ patients was greater than that in pN0
      ones. Both, however, were associated with their clinical nodal stages. In pN+
      patients, Twist, VEGF-C, and VEGFR-3 expressions were 86.11% (31/36), 80.56%
      (29/36), and 58.33% (21/36), respectively. These values were higher than those
      found for pN0 patients (i.e., 13/30, 11/30, and 7/30, respectively) (P < 0.05).
      Among the samples with Twist expression, 88.64% were VEGF-C-positive and 59.09%
      were VEGFR-3-positive. The pN0 counterparts were 4.55% and 9.09%, respectively (P
      < 0.05). The expressions of Twist, VEGF-C, and VEGFR-3 in pN+ patients obtained
      through Western blotting analysis were significantly higher than those in pN0
      patients, and the levels of VEGF-C and VEGFR-3 were positively correlated with
      that of Twist. CONCLUSIONS: Twist expression correlates with lymph node
      metastasis. The mechanism involved in such a correlation may be related to
      lymphangiogenesis.

PMID- 21740803
TI  - Engaging HIV-infected patients in antiretroviral therapy services: CD4 cell count
      testing after HIV diagnosis from 2005 to 2009 in Yunnan and Guangxi, China.
AB  - BACKGROUND: The initiation and expansion of China's national free antiretroviral
      therapy program has led to significant improvement of survival among its
      participants. Success of further scaling up treatment coverage rests upon
      intensifying HIV screening and efficient linkage of care. Timely CD4 cell count
      testing after HIV diagnosis is necessary to determine whether a patient meets
      criteria for antiretroviral treatment, and represents a crucial link to engage
      HIV-infected patients in appropriate care, which has not been evaluated in China.
      METHODS: We evaluated all patients >= 16 years who tested HIV positive from 2005
      to 2009 in Yunnan and Guangxi. Multivariate Logistic regression models were
      applied to identify factors associated with lack of CD4 cell count testing within
      6 months after HIV diagnosis. RESULTS: A total of 83 556 patients were included.
      Over the study period, 30 635 (37%) of subjects received a CD4 cell count within
      6 months of receiving the HIV diagnosis. The rate of CD4 cell count testing
      within 6 months of HIV diagnosis increased significantly from 7% in 2005 to 62%
      in 2009. Besides the earlier years of HIV diagnosis, negative predictors for CD4
      cell count testing in multivariate analyses included older age, not married or
      unclear marriage status, incarceration, diagnosis at sexual transmitted disease
      clinics, mode of HIV transmission classified as men who have sex with men,
      intravenous drug users or transmission route unclear, while minority ethnicity,
      receipt of high school or higher education, diagnosis at voluntary counseling and
      testing clinics, and having HIV positive parents were protective. CONCLUSIONS:
      Significant progress has been made in increasing CD4 testing among newly
      diagnosed HIV positive patients in Yunnan and Guangxi from 2005 - 2009. However,
      a sizable proportion of HIV positive patients still lack CD4 testing within 6
      months of diagnosis. Improving CD4 testing, particularly among patients with
      identified risk factors, is essential to link patients with ART services and
      optimize treatment coverage.

PMID- 21740804
TI  - Prognostic factors associated with rebleeding in cirrhotic inpatients complicated
      with esophageal variceal bleeding.
AB  - BACKGROUND: Esophageal variceal bleeding is a frequent and severe complication in
      patients with cirrhosis. The aim of this study was to identify prognostic factors
      of esophageal variceal rebleeding in cirrhotic inpatients. METHODS: Consecutive
      cirrhotic patients who were admitted to Changhai Hospital because of esophageal
      variceal bleeding were retrospectively analyzed. To assess the independent
      factors for recurrent hemorrhage after esophageal variceal bleeding, medical
      assessment was completed at the time of their initial hospital admission,
      including documentation of clinical, biochemical, and treatment methods that
      might contribute to variceal rebleeding. Univariate and multivariate analyses
      were retrospectively performed. RESULTS: Totally 186 patients (35.8%) were
      assigned to a rebleeding group and the other 334 patients (64.2%) to a non
      rebleeding group. Multivariate stepwise regression analysis showed that four
      variables were positively correlated with rebleeding: Child-pugh grade B (OR =
      2.664, 95%CI 1.680 - 4.223) (compared with Child-pugh grade A), total bilirubin
      (Tbil) (OR = 1.0006, 95%CI 1.002 - 1.0107), creatinine (OR = 1.008, 95%CI 1.002 -
      1.015) and the cumulative volume of blood transfusion (OR = 1.519, 95%CI 1.345 -
      1.716). The presence of ascites (OR = 0.270, 95%CI 0.136 - 0.536) and
      prophylactic antibiotics (OR = 0.504, 95%CI 0.325 - 0.780) were negatively
      correlated with rebleeding of the cirrhotic inpatients. According to standardized
      coefficient, the importance of rebleeding predictors ranked from the most to the
      least was as follows: the cumulative volume of blood transfusion, Child-pugh
      grade B, Tbil and creatinine. CONCLUSION: Rebleeding in cirrhotic inpatients was
      associated with more blood transfusions, Child-pugh grade B, higher Tbil and
      creatinine.

PMID- 21740805
TI  - Variants of tumor necrosis factor-induced protein 3 gene are associated with left
      ventricular hypertrophy in hypertensive patients.
AB  - BACKGROUND: Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown
      important in cardiac remodeling. The aim of the present study was to investigate
      whether the variants of TNFAIP3 gene are associated with left ventricular
      hypertrophy (LVH) in hypertensive patients. METHODS: Four representatives of all
      the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for
      association with hypertrophy in two independent hypertensive populations (n =
      2120 and n = 324). RESULTS: We found that only the tag SNP (rs5029939) was
      consistently lower in the hypertensives with cardiac hypertrophy than in those
      without cardiac hypertrophy in the two study populations, indicating a protective
      effect on LVH (odds ratio (OR) (95% confidence interval (CI)) 0.58 (0.358 -
      0.863), P = 0.035; OR (95%CI) = 0.477 (0.225 - 0.815), P < 0.05, respectively).
      Multiple regression analyses confirmed that the patients with G allele of
      rs5029939 had less thickness in inter-ventricular septum, left ventricular
      posterior wall, relative wall thickness and left ventricular mass index than did
      those with CC allele in the hypertensive patients in both study populations (all
      P < 0.01). CONCLUSION: These findings indicate that the SNP (rs5029939) in the
      TNFAIP3 gene may serve as a novel protective genetic marker for the development
      of LVH in patients with hypertension.

PMID- 21740806
TI  - Motor function and activities of daily living capacity of patients with fractures
      sustained during the Wenchuan earthquake.
AB  - BACKGROUND: On the afternoon of May 12, 2008, a 8.0-magnitude earthquake hit
      Sichuan Province, a mountainous region in Western China, killing about 70 000
      people and leaving over 18 000 missing. What about the survivors motor functions
      and activities of daily living (ADL) capacity, especially for fractures? We need
      the data to guide the rehabilitation for the seismic wounded and it's important
      to collect the data for the future. We study the survivors to understand the
      motor functions and ADL capacity of patients with fractures sustained in the
      Wenchuan earthquake, to provide a basis for rehabilitation and treatment.
      METHODS: We used the Manual Muscle Testing method to evaluate muscle strength,
      the joint angle scale to measure joint range of motion (ROM), and the Barthel
      index to evaluate the activities of daily living status. SPSS 13.0 software was
      used to analyze the data and the results were tested using one-way analysis of
      variance (ANOVA). RESULTS: The number of seismic wounded amounted to 487; 81.1%
      of patients had fractures. Most of the injured had fractures in multiple regions
      (53.9% of all fracture patients), followed by fractures of the upper limb (34.0%
      of patients); cranial fractures were rare (2.3%). Totally 82.0% had restricted
      range of motion, 23.5% had decreased muscle force, and 72.2% of the patients had
      restricted activities of daily living capacities. With time the activities of
      daily living capacity of female increased (P < 0.05), compared with the male
      fracture patients who did not show any relative improvement (P > 0.05). The
      difference between the patients' ages and ADL capacities did not reach
      statistical significance (P > 0.05), nor was there a significant difference
      between their ages and the numbers of days in hospital (P > 0.05). CONCLUSIONS:
      Fractures were the main issue in the seismic wounded, many of them had reductions
      in the ROM, muscle force and ADL capacities. The physicians involved in
      rehabilitation should pay greater attention to muscle force exercises, joint
      mobilization, and occupational therapy during the early phases post disaster.

PMID- 21740807
TI  - Campylobacter enteritis in adult patients with acute diarrhea from 2005 to 2009
      in Beijing, China.
AB  - BACKGROUND: There has been a marked global increase in the incidence of human
      Campylobacter enteritis in recent years. This study investigated the
      epidemiological and clinical features of Campylobacter enteritis in adult
      patients suffering from acute diarrhea. METHODS: This was a retrospective review
      of Campylobacter enteritis in adult patients with acute diarrhea presenting at
      Beijing University First Hospital, Beijing, China, in the summer and autumn
      (April to October) of 2005 to 2009. The data collected included the species of
      campylobacter identified, and the age, gender, clinical manifestations and
      results of laboratory test on stool samples collected from the patients.
      Campylobacter sensitivity tests to various antimicrobial agents were conducted on
      80 specimens. Chi-square tests were applied using SPSS13.0 software and a two
      sided P value of < 0.05 was considered statistically significant. RESULTS:
      Campylobacter spp. isolated from the stool specimens of 142 patients with
      diarrhea represented 14.9% of all the cases examined. C. jejuni was identified in
      127 patients (89.4%) and C. coli in 15 others (10.6%). The infection incidence
      was highest in the age range of 21 - 30 years which comprised 21.7% of the total
      cases examined. Most cases of diarrhea (46 patients) occurred in June. Watery
      diarrhea (97.2%), abdominal pain (72.5%) and fever (64.8%) were the most common
      manifestations of enteric campylobacteriosis. Only four patients (2.8%) had
      bloody diarrhea. The antimicrobial resistance rates were: cefoperazone (100%),
      levofloxacin (61.3%), gentamicin (12.5%), erythromycin (6.3%), and azithromycin
      (2.5%). CONCLUSIONS: Campylobacter was prevalent among adults with acute diarrhea
      from 2005 to 2009 in Beijing, China. The large number of those afflicted by the
      disease warrants the commission of a large multicenter study to determine the
      extent of enteric campylobacteriosis in this region.

PMID- 21740808
TI  - Nested real-time quantitative polymerase chain reaction assay for detection of
      hepatitis B virus covalently closed circular DNA.
AB  - BACKGROUND: Successful treatment of hepatitis B can be achieved only if the
      template for hepatitis B virus (HBV) DNA replication, the covalently closed
      circular HBV DNA (cccDNA) can be completely cleared. To date, detecting cccDNA
      remains clinically challenging. The purpose of this study was to develop a nested
      real-time quantitative polymerase chain reaction (PCR) assay for detecting HBV
      cccDNA in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear
      cells (MMNCs). METHODS: Based on the structural differences between HBV cccDNA
      and HBV relaxed circular DNA (rcDNA), two pairs of primers were synthesized as
      well as a downstream TaqMan probe. Blood and bone marrow samples were collected
      from hepatitis B patients and healthy controls. To remove rcDNA, samples were
      incubated with mung bean nuclease and the resultant purified HBV cccDNA was then
      amplified by nested real-time fluorescence quantitative PCR. The cccDNA levels
      were calculated using a positive standard. RESULTS: The nested real-time
      fluorescence quantitative PCR method for HBV cccDNA was successful, with a linear
      range of 3.0 * 10(2) copies/ml to 3.9 * 10(8) copies/ml. Of the 25 PBMC samples
      and 7 MMNC samples obtained from chronic hepatitis B or liver cirrhosis patients,
      3 MMNC samples and 9 PBMC samples were positive for HBV cccDNA, while all of the
      21 PBMC samples from healthy controls were negative. CONCLUSION: The nested real
      time fluorescence quantitative PCR may be used as an important tool for detecting
      cccDNA in hepatitis B patients.

PMID- 21740809
TI  - Higher proportions of peripheral CD19+CD5+ B cells predict the effect of
      corticosteroid in patients with late-onset hemorrhagic cystitis after allogeneic
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: The cause of late-onset hemorrhagic cystitis (LOHC) after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) remains obscure. In clinical
      practice, some LOHC patients respond to immunosuppression. The aim of this study
      was to determine the immune pathogenesis of LOHC post allo-HSCT. METHODS: With
      the diagnosis of LOHC, patients were given initial treatment consisting of fluid
      hydration, alkalization and forced diuresis, and empirical anti-viral therapy for
      10 - 14 days or until a week after the virus became negative. The nonresponders
      were applied corticosteroid. Seven to ten days later, patients' response was
      evaluated. Along with treatment, CD19(+) B lymphocyte subsets were measured at
      various study points. RESULTS: From October 2009 to March 2010, we found 28 cases
      of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except
      that three cases were not treated according to the protocol, the other 25 cases
      were divided into three groups: anti-virus responders (Group A, n = 6),
      corticosteroid responders (Group B1, n = 16), corticosteroid and anti-virus
      nonresponders (Group C, n = 3) according to their clinical response. Percentages
      of CD19(+)CD5(+) B lymphocytes were not significantly different among three
      groups at onset of LOCH. However, in Group B1 after the first anti-virus phase,
      percentages of CD19(+)CD5(+) lymphocytes significantly increased comparing with
      those at onset (P = 0.022), and then significantly decreased at PR (P = 0.003)
      and CR (P = 0.002) with corticosteroid treatment. But significant change was not
      observed in Groups A and C. CONCLUSION: The immune etiology seems to be involved
      in the development of LOHC and the proportion of CD19(+)CD5(+) lymphocytes may
      serve as a cellular biomarker to predict the response to corticosteroid in LOHC.

PMID- 21740810
TI  - SNCG shRNA suppressed breast cancer cell xenograft formation and growth in nude
      mice.
AB  - BACKGROUND: Overexpression of breast cancer-specific gene 1 (SNCG) is associated
      with poor prognosis in advanced breast cancer patients. This study aimed to
      determine the effects of SNCG knockdown in breast cancer cells by using small
      hairpin RNA (shRNA). METHODS: Four different SNCG shRNA oligonucleotides were
      designed and chemically synthesized to construct mammalian expression vectors.
      These vectors were then stably transfected into a breast cancer MCF-7 cell line
      to knockdown SNCG expression. After SNCG knockdown was confirmed, the stable cell
      lines were inoculated into nude mice. SNCG mRNA and protein expressions were
      analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT
      PCR) and immunohistochemistry, respectively in both the stable cell lines and
      xenografts. RESULTS: All four SNCG shRNA constructs significantly reduced SNCG
      mRNA and protein levels in MCF-7 cells, as compared to the unrelated sequence
      control shRNA and the liposome control mice (P < 0.05). SNCG-knockdown MCF-7
      cells formed significantly smaller tumor masses than cells expressing the
      unrelated sequence control or the liposome control mice (P < 0.05). CONCLUSION:
      SNCG shRNA effectively suppressed breast cancer cell formation in vivo and may be
      a useful clinical strategy to control breast cancer.

PMID- 21740811
TI  - Effect of low-dose fenvalerate on semen quality capacitation in adult mice.
AB  - BACKGROUND: Fenvalerate (FEN) has been demonstrated to be a reproductive toxicant
      in humans and rodents. However, little is known about whether short-term exposure
      to low-dose FEN produces reproductive toxicity. METHODS: We administered FEN
      (0.009 375, 0.1875, 3.750, or 45.00 mg*kg(-1)*d(-1) by gavage for 30 days) to
      male ICR mice and compared reproductive toxicity parameters between groups
      receiving different concentrations of FEN. Reproductive toxicity was evaluated by
      computer-assisted semen quality analysis (CASA), chlortetracycline (CTC) assay,
      and histopathology. RESULTS: The sperm morphology and testis histology of FEN
      exposed mice (all doses) were similar to that in controlling mice. Exposure to
      FEN at a concentration of 0.1875 mg*kg(-1)*d(-1) decreased sperm path
      straightness (STR) and linearity (LIN) (both P < 0.05), but had no significant
      impact on average path velocity (VAP), straight line velocity (VSL), curvilinear
      velocity (VCL), lateral amplitude (ALH), beat cross frequency (BCF), or
      progressive motility (MOT). FEN reduced the rate of mouse sperm capacitation in a
      dose-dependent manner. CONCLUSION: The present results demonstrate that exposure
      to low-dose FEN for 30 days reduces semen quality and sperm capacitation in adult
      mice.

PMID- 21740812
TI  - Human umbilical cord mesenchymal stem cells derived from Wharton's jelly
      differentiate into insulin-producing cells in vitro.
AB  - BACKGROUND: Islet transplantation is an effective way of reversing type I
      diabetes. However, islet transplantation is hampered by issues such as immune
      rejection and shortage of donor islets. Mesenchymal stem cells can differentiate
      into insulin-producing cells. However, the potential of human umbilical cord
      mesenchymal stem cells (huMSCs) to become insulin-producing cells remains
      undetermined. METHODS: We isolated and induced cultured huMSCs under islet cell
      culture conditions. The response of huMSCs were monitored under an inverted phase
      contrast microscope. Immunocytochemical and immunofluorescence staining methods
      were used to measure insulin and glucagon protein levels. Reverse transcription
      polymerase chain reaction (RT-PCR) was performed to detect gene expression of
      human insulin and PDX-1. Dithizone-staining was employed to determine the zinc
      contents in huMSCs. Insulin secretion was also evaluated through
      radioimmunoassay. RESULTS: HuMSCs induced by nicotinamide and beta
      mercaptoethanol or by neurogenic differentiation 1 gene (NeuroD1) transfection
      gradually changed morphology from typically elongated fibroblast-shaped cells to
      round cells. They had a tendency to form clusters. Immunocytochemical studies
      showed positive expression of human insulin and glucagon in these cells in
      response to induction. RT-PCR experiments found that huMSCs expressed insulin and
      PDX-1 genes following induction and dithizone stained the cytoplasm of huMSCs a
      brownish red color after induction. Insulin secretion in induced huMSCs was
      significantly elevated compared with the control group (t = 6.183, P < 0.05).
      CONCLUSIONS: HuMSCs are able to differentiate into insulin-producing cells in
      vitro. The potential use of huMSCs in beta cell replacement therapy of diabetes
      needs to be studied further.

PMID- 21740813
TI  - Reduced brain-derived neurotrophic factor expression in cortex and hippocampus
      involved in the learning and memory deficit in molarless SAMP8 mice.
AB  - BACKGROUND: The molarless condition has been reported to compromise learning and
      memory functions. However, it remains unclear how the molarless condition
      directly affects the central nervous system, and the functional consequences on
      the brain cortex and hippocampus have not been described in detail. The aim of
      this study was to find the molecular mechanism related with learning and memory
      deficit after a bilateral molarless condition having been surgically induced in
      senescence-accelerated mice/prone 8 (SAMP8) mice, which may ultimately provide an
      experimental basis for clinical prevention of senile dementia. METHODS: Mice were
      either sham-operated or subjected to complete molar removal. The animals' body
      weights were monitored every day. Learning ability and memory were measured in a
      water maze test at the end of the 1st, 2nd, and 3rd months after surgery. As soon
      as significantly prolonged escape latency in the molarless group was detected,
      the locomotor activity was examined in an open field test. Subsequently, the
      animals were decapitated and the cortex and hippocampus were dissected for
      Western blotting to measure the expression levels of brain-derived neurotrophic
      factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity
      receptor of BDNF. RESULTS: Slightly lower weights were consistently observed in
      the molarless group, but there was no significant difference in weights between
      the two groups (P > 0.05). Compared with the sham group, the molarless group
      exhibited lengthened escape latency in the water maze test three months after
      surgery, whereas no difference in locomotor activity was observed. Meanwhile, in
      the cortex and hippocampus, BDNF levels were significantly decreased in the
      molarless group (P < 0.05); but the expression of its receptor, TrkB, was not
      significantly affected. CONCLUSION: These results suggested that the molarless
      condition impaired learning and memory abilities in SAMP8 mice three months after
      teeth extraction, and this effect was accompanied by significantly reduced BDNF
      expression in the cortex and hippocampus.

PMID- 21740814
TI  - Microarray profiles on age-related genes in the earlier postnatal rat visual
      cortex.
AB  - BACKGROUND: Accumulating evidence indicates that both innate and adaptive
      mechanisms are responsible for the postnatal development of the mammalian visual
      cortex. Most of the studies, including gene expression analysis, were performed
      on the visual cortex during the critical period; few efforts were made to
      elucidate the molecular changes in the visual cortex during much earlier
      postnatal stages. The current study aimed to gain a general insight into the
      molecular mechanisms in the developmental process of the rat visual cortex using
      microarray to display the gene expression profiles of the visual cortex on
      postnatal days. METHODS: All age-matched Sprague-Dawley rats in various groups
      including postnatal day 0 (P0, n = 20), day 10 (P10, n = 15), day 20 (P20, n =
      15) and day 45 (P45, n = 10) were sacrificed respectively. Fresh visual cortex
      from the binocular area (Area 17) was dissected for extraction of total RNA for
      microarray analyses. Taking advantage of annotation information from the gene
      ontology and pathway database, the gene expression profiles were systematically
      and globally analyzed. RESULTS: Of the 31 042 gene sequences represented on the
      rat expression microarray, more than 4000 of the transcripts significantly
      altered at days 45, 20 or 10 compared to day 0. The most obvious alteration of
      gene expression occurred in the first ten days of the postnatal period and the
      genomic activities of the visual cortex maintained a high level from birth to day
      45. Compared to the gene expression at birth, there were 2630 changed transcripts
      that shared in three postnatal periods. The up-regulated genes in most signaling
      pathways were more than those of the down-regulated genes. CONCLUSIONS: Analyzing
      gene expression patterns, we provide a detailed insight into the molecular
      organization of the developing visual cortex in the earlier postnatal rat. The
      most obvious alteration of gene expression in visual cortex occurred in the first
      ten days. Our data were a basis to identify new relevant candidate genes that
      control visual cortex development.

PMID- 21740815
TI  - Regulation of epithelial sodium channel alpha-subunit expression by adenosine
      receptor A2a in alveolar epithelial cells.
AB  - BACKGROUND: The amiloride-sensitive epithelial sodium channel alpha-subunit
      (alpha-ENaC) is an important factor for alveolar fluid clearance during acute
      lung injury. The relationship between adenosine receptor A(2a) (A(2a)AR)
      expressed in alveolar epithelial cells and alpha-ENaC is poorly understood. We
      targeted the A(2a)AR in this study to investigate its role in the expression of
      alpha-ENaC and in acute lung injury. METHODS: A549 cells were incubated with
      different concentrations of A(2a)AR agonist CGS-21680 and with 100 umol/L CGS
      21680 for various times. Rats were treated with lipopolysaccharide (LPS) after
      CGS-21680 was injected. Animals were sacrificed and tissue was harvested for
      evaluation of lung injury by analysis of the lung wet-to-dry weight ratio, lung
      permeability and myeloperoxidase activity. RT-PCR and Western blotting were used
      to determine the mRNA and protein expression levels of alpha-ENaC in A549 cells
      and alveolar type II epithelial cells. RESULTS: Both mRNA and protein levels of
      alpha-ENaC were markedly higher from 4 hours to 24 hours after exposure to 100
      umol/L CGS-21680. There were significant changes from 0.1 umol/L to 100 umol/L
      CGS-21680, with a positive correlation between increased concentrations of CGS
      21680 and expression of alpha-ENaC. Treatment with CGS-21680 during LPS induced
      lung injury protected the lung and promoted alpha-ENaC expression in the alveolar
      epithelial cells. CONCLUSION: Activation of A(2a)AR has a protective effect
      during the lung injury, which may be beneficial to the prognosis of acute lung
      injury.

PMID- 21740816
TI  - Menin expression is regulated by transforming growth factor beta signaling in
      leukemia cells.
AB  - BACKGROUND: Menin is a ubiquitously expressed protein encoded by the multiple
      endocrine neoplasia type 1 (MEN1) gene. Besides its importance in endocrine
      organs, menin has been shown to interact with the mixed lineage leukemia (MLL)
      protein, a histone H3 lysine 4 methyltransferase, and plays a critical role in
      hematopoiesis and leukemogenesis. Previous studies have shown that menin promotes
      transforming growth factor beta (TGF-beta) signaling in endocrine cells. However,
      little is known regarding the impact of TGF-beta pathway on menin in
      hematopoietic system. Here, with leukemia cell lines generated from conditional
      MEN1 or TGF-beta receptor (TbetaRII) knockout mouse models, we investigated the
      possible cross-talk of these two pathways in leukemia cells. METHODS: MEN1 or
      TbetaRII conditional knockout mice were bred and the bone marrow cells were
      transduced with retroviruses expressing oncogeneic MLL-AF9 (a mixed lineage
      leukemia fusion protein) to generate two leukemia cell lines. Cell proliferation
      assays were performed to investigate the effect of TGF-beta treatment on MLL-AF9
      transformed leukemia cells with/without MEN1 or TbetaRII excision. Menin protein
      was detected with Western blotting and mRNA levels of cell proliferation-related
      genes Cyclin A(2) and Cyclin E(2) were examined with real-time RT-PCR for each
      treated sample. In vivo effect of TGF-beta signal on menin expression was also
      investigated in mouse liver tissue after TbetaRII excision. RESULTS: TGF-beta not
      only inhibited the proliferation of wild type MLL-AF9 transformed mouse bone
      marrow cells, but also up-regulated menin expression in these cells. Moreover,
      TGF-beta failed to further inhibit the proliferation of Men1-null cells as
      compared to Men1-expressing control cells. Furthermore, excision of TbetaRII, a
      vital component in TGF-beta signaling pathway, down-regulated menin expression in
      MLL-AF9 transformed mouse bone marrow cells. In vivo data also confirmed that
      menin expression was decreased in liver samples of conditional TbetaRII knockout
      mice after TbetaRII excision. CONCLUSION: These results provided the first piece
      of evidence of cross-talk between menin and TGF-beta signaling pathways in
      regulating proliferation of leukemia cells, suggesting that manipulating the
      cross-talk of the two pathways may lead to a novel therapy for leukemia.

PMID- 21740817
TI  - Diagnostic value of tumor marker pro-gastrin-releasing peptide in patients with
      small cell lung cancer: a systematic review.
AB  - BACKGROUND: Lung cancer is one of the most common malignancies in the world and
      one of the leading cancers that result in death. The aim of this study was to
      evaluate and compare the diagnostic value of the serum tumor marker pro-gastrin
      releasing peptide 31-98 (ProGRP31-98) to pathological diagnosis as reference
      standard in patients with suspected small cell lung cancer (SCLC). METHODS:
      Literature searches covering 1978 through to 2009 were performed in Pubmed, OVID,
      MEDLINE, EMbase, Cancerlit, China National Knowledge Infrastructure (CNKI), and
      CBM using the key search words; 'small cell lung cancer', 'tumor marker',
      'ProGRP31-98' and 'diagnostic tests', 'ELISA', 'EIA' and 'diagnostic accuracy'.
      Studies were collected and data analyzed to evaluate the diagnostic value of
      serum ProGRP31-98 levels for the diagnosis of SCLC compared with pathology.
      Eligibility criteria for inclusion in the analysis were based on criteria for
      diagnostic research published by the Cochrane Screening and Diagnostic Tests
      METHODS: Group (SDTMG). The characteristics of the included articles were
      appraised and the data were extracted from the original articles for further
      statistical analysis of study heterogeneity using Review Manager 4.2 software.
      Based on study heterogeneity analysis, a suitable 'effect' model was selected to
      calculate pooled sensitivity and specificity by meta-analysis. A Summary Receiver
      Operating Characteristic (SROC) curve and the area under the curve (AUC) were
      generated and sensitivity analysis conducted. RESULTS: A total of 22 articles
      were entered into this meta-review, including 11 English articles with a quality
      at level C. In total, the studies involved 6759 subjects, of which 1470 were
      diagnosed with SCLC by pathology, and 5289 subjects diagnosed with non-SCLC
      (NSCLC). The meta-analysis showed that heterogeneity among studies was high (P =
      0.00001, I(2) = 86.8%). With ELISA, the pooled sensitivity was 0.72 (0.70 to 0.75
      at 95%CI) and the pooled specificity was 0.93 (0.92 to 0.94 at 95%CI); the SROC
      and the AUC were 0.8817. These data suggest that ProGRP31-98 has a relatively
      high rate of missed diagnosis (28%), but a relatively low rate of misdiagnosis
      (7%). CONCLUSION: From meta-analysis, we concluded that serum ProGRP31-98 is a
      valuable marker with a high specificity for diagnosis of SCLC with a similar
      diagnostic accuracy to pathology.

PMID- 21740818
TI  - Cigarette smoking inhibits the anti-platelet activity of aspirin in patients with
      coronary heart disease.
AB  - OBJECTIVE: Tobacco smoking results in increased platelet aggregability, which
      suggests that low-dose aspirin used in common clinical practice may not
      effectively inhibit platelet activity in smokers with coronary heart disease
      (CHD). This review was performed to assess the effect of aspirin on platelet
      aggregation in patients with CHD. DATA SOURCES: We performed an electronic
      literature search of MEDLINE (starting from the beginning to March 15, 2009)
      using the term "smoking" or "tobacco" paired with the following: "platelet",
      "aspirin" or "coronary heart disease". STUDY SELECTION: We looked for review
      articles regarding the effect of tobacco smoking on platelet activity and on the
      anti-platelet efficacy of aspirin in healthy people and patients with CHD. The
      search was limited in "core clinical journal". In total, 1321 relevant articles
      were retrieved, and 36 articles were ultimately cited. RESULTS: Tobacco smoking
      results in increased platelet aggregability, which can be inhibited by low-dose
      aspirin in the healthy population. However, in patients with CHD, the increased
      platelet aggregability can not be effectively inhibited by the same low-dose of
      aspirin. A recent study indicated that clopidogrel or an increased dose of
      aspirin can effectively inhibit the increased platelet aggregability induced by
      tobacco smoking in patients with CHD. CONCLUSIONS: It is important for patients
      with CHD to quit smoking. For the current smoker, it may be necessary to take
      larger doses of aspirin than normal or take an adenosine diphosphate receptor
      inhibitor along with aspirin to effectively inhibit the increased platelet
      activity.

PMID- 21740819
TI  - Inhibitory effect of 2'-o-methoxyethyl-modified antisense oligonucleotides
      targeting vascular endothelial growth factor A on SKOV3 human ovarian cancer
      cells.
AB  - BACKGROUND: Ovarian cancers are often at an advanced stage at diagnosis because
      early detection is difficult. The poor prognosis of ovarian cancers highlights
      the crucial need to develop better therapeutic agents and strategies. The
      objective of this study was to investigate the inhibitory effects of a new
      modified antisense oligonucleotides targeting vascular endothelial growth factor
      A (VEGF-A) in SKOV3 ovarian cancer cells. METHODS: Antisense oligonucleotides
      targeting VEGF-A was designed, synthesized and transfected into SKOV3 ovarian
      cancer cells. Western blotting and real-time RT-PCR were used to analyze the
      inhibitory effects of antisense oligonucleotides on VEGF-A protein and mRNA
      expression. Transwell matrix assay was used to detect cell migration inhibition.
      RESULTS: The antisense oligonucleotides targeting VEGF-A significantly decreased
      VEGF-A protein and mRNA expression and inhibited cell migration in SKOV3 ovarian
      cancer cells. CONCLUSIONS: This new modified antisense oligonucleotides targeting
      VEGF-A can decrease VEGF-A expression and inhibit cell migration in SKOV3 ovarian
      cancer cells. This new oligonucleotides may be a promising therapeutic agent for
      ovarian cancers.

PMID- 21740820
TI  - Viral shedding in Chinese young adults with mild 2009 H1N1 influenza.
AB  - BACKGROUND: The duration of viral shedding and the transmission of 2009 H1N1
      influenza among individuals, especially among the younger population with mild
      illness, are not well understood now. The aim of this study was to determine the
      viral shedding of the young adult patients with mild 2009 H1N1 influenza in
      China. METHODS: From September 2009 to January 2010, the clinical data and serial
      nasopharyngeal swabs of 67 patients with 2009 H1N1 influenza and 37 patients with
      seasonal influenza aged from 18 years to 35 years were collected. The
      nasopharyngeal swab samples were detected by real time RT-PCR to determine the
      viral shedding. All the patients did not receive the antiviral therapy but
      Chinese medicine for detoxicating. RESULTS: Among the patients with H1N1 virus
      infection, 82.1% (55/67) patients presented with fever symptom, while more
      patients with high fever (>= 39 degrees C) were found in seasonal influenza
      patients (P < 0.05). For the H1N1 patients, the median interval between the
      symptom onset and the undetectable RNA was six days (4 - 10 days). But viral
      shedding was still found in 31.3% patients after 7 days following illness onset.
      The median interval between disappearance of fever and an undetectable viral RNA
      level was three days (2 - 8 days), and 17.9% patients were found to be viral
      shedding 6 days later after normalization of body temperature. For the seasonal
      influenza patients, 94.6% patients were detected out viral RNA within 7 days. The
      median interval of seasonal influenza between the symptom onset and the
      undetectable RNA was four days (3 - 8 days). The median interval between
      disappearance of fever and an undetectable viral RNA level was three days (2 - 6
      days). CONCLUSION: It suggests that 7 days isolation period from the illness
      onset or 24 hours after the resolution of fever and respiratory symptoms are not
      long enough to cut off the transmission among Chinese young adults with mild
      illness.

PMID- 21740821
TI  - Single plus one port laparoscopic radical prostatectomy: a report of 8 cases in
      one center.
AB  - Laparoscopic radical prostatectomy is considered the first treatment of choice
      for local prostate cancer due to its minimal invasion advantage. To further
      achieve the goal of minimal invasion, single port laparoscopic radical
      prostatectomy has been developed to minimize the complications associated with
      puncture tracks. The aim of this study was to illustrate the technique for single
      port laparoscopic radical prostatectomy and evaluate its efficacy and safety. We
      reported 8 cases of radical prostatectomy with excellent early outcome carried
      out in Shanghai Changzheng Hospital from June 2009 to August 2009 using a home
      made multiple instrument access port and adding an additional small incision at
      McBurney point.

PMID- 21740822
TI  - A novel mutation in TPRS1 gene caused tricho-rhino-phalangeal syndrome in a
      Chinese patient with severe osteoporosis.
AB  - Tricho-rhino-phalangeal syndrome (TRPS) was first reported in 1966. Although
      mutation of TRPS1 gene is considered to be responsible for the syndromes in 2000,
      investigation of bone metabolism and changes of serum insulin-like growth factor
      (IGF)-1 level in this kind of patients is rare. Here, we report a patient with
      TRPS I (MIM 190350) presenting a novel mutation (1096insA) and abnormal changes
      of severe osteoporosis as well as low serum IGF-I level.

PMID- 21740823
TI  - Atrium-atrioventricular node block: an unusual complication during catheter
      ablation of persistent atrial fibrillation.
AB  - Ablation of persistent atrial fibrillation is still a challenge for the
      ablationist. Extensive ablation is required under some conditions and could lead
      to some unintended complications. Here we report a case of atrium
      atrioventricular node block complicating multiple catheter ablation procedures
      for persistent atrial fibrillation. After extensive ablation, including
      circumferential pulmonary vein ablation, linear ablation at the left atrial roof,
      mitral isthmus, atrial septum, cavotricuspid isthmus, and complex fractionated
      atrial electrogram ablation, conduction obstacle was found, and sinus impulse
      could not travel from the right atrium, atrial septum and left atrium to
      atrioventricular node. The case indicated that intensive ablation at some key
      sites, especially the interatrial septum, should be careful during ablation of
      atrial fibrillation.

PMID- 21740824
TI  - Right phrenic injury after radiofrequency catheter ablation of atrial tachycardia
      at crista terminalis.
AB  - A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia
      with a foci located at the root of the upper crista terminalis was found to have
      right diaphragm paresis after receiving a total of 8 radiofrequency energy
      deliveries (40-60 W, 50-60oC) and a total duration of 540 seconds of ablation
      therapy (7Fr 8 mm deflectable ablation catheter). The right diaphragm paresis
      remained resolved up to 14 months after the procedure as confirmed by repeated
      chest X-rays.

PMID- 21740825
TI  - Bullet migration from the knee to the heart after a gunshot injury: a case
      report.
AB  - Migration of a bullet to a distant part of the body after a gunshot is rarely
      observed in the clinical setting, and migration to the heart is even rarer. There
      are usually no clear symptoms or signs from migration of a bullet. The bullet can
      be easily missed and sometimes identified in a review examination. A case of
      bullet migration to the heart 2 months after a gunshot to the left knee was
      reported.

PMID- 21740826
TI  - Psoriasis complicated with venous thromboembolism: report of two cases and a
      literature review.
AB  - Cases of psoriasis complicated with venous thromboembolism are rarely reported.
      Here, we report two cases and review the current literature on the subject. Two
      patients with long-standing severe psoriasis presented with chest pain, shortness
      of breath and breathing difficulties. The patients were diagnosed using lung
      ventilation-perfusion scans or computed tomographic pulmonary angiography.
      Anticoagulation or thrombolytic therapy was initiated, and long-term continuous
      anticoagulation with warfarin prevented any recurrences.

PMID- 21740827
TI  - Intracranial malignant meningioma with cerebrospinal fluid dissemination: a case
      report.
AB  - Malignant meningiomas are uncommon intracranial tumors. The metastasis of
      malignant meningiomas to distant extracranial sites are well known. However,
      dissemination of the tumours in the cerebrospinal fluid (CSF) is rare and few
      cases have been reported. We present a case of histologically proven malignant
      meningioma with CSF dissemination at the remote intracranial area and into the
      spinal canal detected with magnetic resonance imaging.

PMID- 21740828
TI  - Treatment of glomerulonephritis associated with hepatitis C virus in patient with
      cirrhosis: only pegylated interferon and ribavirin.

PMID- 21740829
TI  - Telmisartan, ramipril, or both in high-risk Chinese patients: analysis of
      ONTARGET China data.
AB  - BACKGROUND: The results from the ONgoing Telmisartan Alone and in combination
      with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin
      receptor blocker telmisartan was not inferior to the angiotensin-converting
      enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular
      death, myocardial infarction, stroke or hospitalization for congestive heart
      failure in high-risk patients, and telmisartan was associated with slightly
      superior tolerability. The combination of the two drugs was associated with more
      adverse events without an increase in benefit. This study aimed to analyze the
      data from ONTARGET obtained from a subgroup of patients enrolled in China and to
      evaluate the demographic and baseline characteristics, the compliance, efficacy,
      and safety of the different treatment strategies in randomized patients in China.
      METHODS: A total of 1159 high-risk patients were randomized into three treatment
      groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to
      receive 10 mg of ramipril and 384 assigned to receive both study medications. The
      median follow-up period was 4.3 years. RESULTS: The mean age of Chinese patients
      was 65.6 years, 73.6% of patients were male. The proportion of patients with
      stroke/transient ischemic attacks at baseline in China was two times more than
      the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion
      of permanent discontinuation of study medication due to cough was 0.5% in the
      telmisartan group, which was much less than that in the combination or the
      ramipril group. There were no significant differences in the incidence of primary
      outcome among three treatment groups of Chinese patients. More strokes occurred
      in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater
      systolic blood pressure reduction (-9.8 mmHg), and more renal function failure
      were noted in the combination treatment group than in the ramipril or telmisartan
      group (2.6% vs. 1.6% and 1.0%). CONCLUSIONS: There was no evidence that the
      results of ONTARGET differed between Chinese patients and the entire study
      population with respect to the incidence of primary outcome, particularly safety.
      Compliance with study medications was good. The evidence from ONTARGET indicated
      that the treatment strategies in ONTARGET were applicable to patients in China.

PMID- 21740830
TI  - Molecular epidemiology of serotype 19A Streptococcus pneumoniae isolated from
      children in Beijing, 1997-2006.
AB  - BACKGROUND: Despite the prevalence of Streptococcus pneumoniae serotype 19A, the
      molecular characteristics of this serotype are yet to be fully elucidated. The
      aim of this study was therefore to determine the homology of the serotype 19A in
      China. METHODS: Pulsed-field gel electrophoresis and multilocus sequence typing
      were done to these forty-nine serotype 19A isolates to investigate the
      relationship between the strains prevalent in Beijing and other regions. RESULTS:
      From 1997 to 2006, the percentage of serotype 19A isolates increased. The
      susceptibility rate to penicillin and amoxicillin decreased and the resistance
      rate to cefuroxime increased. ST320 was the most prevalent ST, followed by
      ST3546. There were six new STs identified in our study. The serotype 19A strains
      were classified into six different pulsed-field gel electrophoresis (PFGE)
      patterns. ST320, which was associated with two different PFGE patterns (A and D),
      accounted for 32 isolates, and ST3546, which was associated with two PFGE
      patterns (B and E), accounted for eight isolates. CONCLUSIONS: From 2003 onwards,
      ST320 was the most common ST and the rate of resistance to cefuroxime increased
      significantly. Further long-term surveys of Streptococcus pneumoniae serotype 19A
      are required to monitor ST prevalence and antimicrobial resistance in this
      important human pathogen.

PMID- 21740831
TI  - Forkhead box protein 3 mRNA expression in the peripheral blood of kidney
      transplant recipients with acute rejection.
AB  - BACKGROUND: Regulatory T cells (Tregs) are immunologically and clinically
      interesting not least because of the important role they play in allograft
      rejection. Likewise, expression of the transcription factor forkhead box protein
      3 (FOXP3), detected in transplant biopsies, is also of interest because of its
      role in the development of regulatory T cells. In this study, we investigated the
      relationship between FoxP3 mRNA expression and acute organ rejection in kidney
      transplant recipients. METHODS: In this prospective study, FoxP3 mRNA expression
      levels in peripheral blood samples from 10 recipients of living relative-donor
      kidney transplants were measured before transplantation as well as at the 14th
      and 90th days post-transplantation. In addition, 46 first-time kidney-transplant
      recipients participated in a cross-sectional study, with 28 patients classified
      as having acute organ rejection; whilst the remaining 18 patients had
      functionally stable allografts. FoxP3 mRNA expression levels in peripheral blood
      samples were compared between these two different groups. RESULTS: Before
      transplantation mean FoxP3 mRNA levels vs. GADPH mRNA levels (lg(FoxP3 mRNA/GADPH
      mRNA)) in the 10 recipients were 1.11 +/- 0.67. The mean FoxP3 mRNA expression
      levels measured at 14th and 90th days post-transplantation were significantly
      higher than before transplantation (1.69 +/- 0.38, P = 0.03; 1.44 +/- 0.21, P =
      0.04, respectively). Additionally, the mean FoxP3 mRNA levels vs. GADPH mRNA
      expression levels (lg(FoxP3 mRNA/GADPH mRNA)) were significantly higher in
      recipients suffering acute rejection compared with those with stable allografts
      (1.77 +/- 0.61 and 1.43 +/- 0.27, respectively, P = 0.03). CONCLUSIONS: After
      kidney transplantation, FoxP3 mRNA levels were found to increase in the
      peripheral blood of all recipients. Considerably higher FoxP3 mRNA levels were
      observed in recipients suffering acute rejection. These results suggest that
      FoxP3 mRNA levels in peripheral blood samples can be used as a diagnostic tool
      for identifying acute rejection.

PMID- 21740832
TI  - Treatment of depression using sleep electroencephalogram modulated repetitive
      transcranial magnetic stimulation.
AB  - BACKGROUND: As a treatment of depression, the efficacy of conventional repetitive
      transcranial magnetic stimulation (rTMS) is limited, and symptoms recurrence is
      easy to occur after the treatment. This study aimed to examine the efficacy and
      safety of sleep electroencephalogram modulated repetitive rTMS (SEM-rTMS) in the
      treatment of depression. METHODS: After 7 days without psychoactive medication,
      164 patients with clinically defined depression were randomly divided into 3
      groups: SEM-rTMS group (n = 57), conventional rTMS (C-rTMS, n = 55) group and
      sham-rTMS group (n = 52). Every patient was treated with the corresponding method
      for 30 minutes everyday for 10 days. Before and after scores on the 24-item
      Hamilton rating scale for depression (HAMD-24) and the clinical outcome on the
      10th day of therapy for all subjects were analyzed. RESULTS: Twenty-two cases in
      the SEM-rTMS group obtained improved mood as compared to 6 in the C-rTMS group
      and 2 in the sham-rTMS group (chi(2) = 15.89, P = 0.0004). After completion of
      the rTMS phase of the protocol, a (51 +/- 5)% reduction of HAMD-24 scores from
      the baseline in the SEM-rTMS group was found compared with a (34 +/- 4)% in the C
      rTMS group (q = 26.09, P = 0.001) and a (14 +/- 3)% in sham-rTMS group (q =
      57.53, P = 0.000). The 88% total effective rate in the SEM-rTMS group was
      significantly higher than 68% in the C-rTMS group and 20% in the sham-rTMS group
      (chi(2) = 12.01, P = 0.0025). No significant side effects were noted. CONCLUSION:
      SEM-rTMS is an effective and safe way for treating depression with repetitive
      transcranial magnetic stimulation (ChiCTR-TRC-00000438).

PMID- 21740833
TI  - Treatment strategies and indications for interventional management of
      pseudoaneurysms.
AB  - BACKGROUND: Pseudoaneurysms (PAs) are common vascular abnormalities predominantly
      arising from a disruption in the integrity of the arterial wall. The potential
      complications of PAs are usually unpredictable and carry high rates of morbidity
      and mortality. This paper presents our experience with various treatment
      strategies for PAs. METHODS: Fifty-four patients with 55 PAs were diagnosed by
      non-invasive imaging examination. The etiology of PAs included trauma (33/55),
      infection (5/55), iatrogenic (6/55), and idiopathic (11/55). Different procedures
      including ultrasound (US)-guided compression, endovascular treatment, and surgery
      were performed depending on the location of PAs, size of the sac and neck, and
      characteristics of the donor artery. The methods of endovascular treatment
      included embolization of parent artery, the PA sac, or implantation of a stent
      graft. Follow-up was performed using US or CT and ranged from 1 day to 24 months
      (average 16.7 months). RESULTS: In all 54 patients, 3 patients with superficial
      PAs were treated by US-guided compression, while 44 patients with 45 PAs located
      in the head and neck (n = 20), viscera (n = 10) or extremities (n = 15) were
      treated by endovascular treatment. Nine patients with PAs located in the head and
      neck (n = 2) or extremities (n = 7) were treated by surgery. Among them, one
      patient underwent endovascular treatment combined with surgery and 1 was treated
      by surgery after unsuccessful US-guided compression. In the 3 patients treated
      with US-guided compression, 2 were successfully treated while the remaining
      patient required additional surgery. Primary technical success of endovascular
      management was 97.7% (43/44) and the cure rate was 95.5% (42/44). In the surgery
      group, 4 patients recovered well, 1 patient was cured by endovascular treatment
      combined with surgery, 2 cases underwent amputation, 1 patient died of multi
      organ failure and 1 patient was paralysed. CONCLUSIONS: Minimally invasive
      interventional techniques are established treatment methods for PA with favorable
      success rates and minimal morbidity. The therapeutic options should be tailored
      to the location, size and rupture risk of PA, condition of the donor artery and
      existing comorbidity.

PMID- 21740834
TI  - Breast magnetic resonance imaging in patients with occult breast carcinoma:
      evaluation on feasibility and correlation with histopathological findings.
AB  - BACKGROUND: As an uncommon presentation, occult primary breast cancer remains a
      diagnostic and therapeutic challenge in clinical practice. This study aimed to
      retrospectively assess the feasibility of breast magnetic resonance imaging (MRI)
      in patients with malignant axillary lymphadenopathy and unknown primary
      malignancy, and correlation with histopathological characteristics. METHODS: A
      total of 35 women with occult breast carcinoma were evaluated with dynamic
      contrast-enhanced breast MRI. Whole seriate section was used in all cases. MRI
      performance was assessed and correlated with histopathological findings. RESULTS:
      Twenty-one of 35 patients were found to have primary breast carcinoma
      histologically. Twenty of the 21 patients had abnormal MR findings and 1 patient
      had a normal MRI study. Of the remaining 14 patients, 10 were negative on both
      MRI and surgery. Four had suspicious enhancement on MRI and no corresponding
      tumor was found. Lesions with mass enhancement were found in 55% (11/20) and
      ductual and segmental enhancement in 45%. The average diameter of the primary
      tumors was 15 mm. Invasive ductal carcinomas were found in 81% (17/21). One of 17
      invasive ductual carcinomas was too small to be graded. Fourteen of the remaining
      16 were classified as grade II and 2 as grade I. Thirty-two of the 35 patients
      had received estrogen receptor, progesterone receptor and human epidermal growth
      factor receptor 2 examinations and the 12 of 32 were triple-negative breast
      carcinoma. CONCLUSIONS: Mass lesions with small size and lesions with ductal or
      segment enhancement are common MRI features in patients with occult breast
      cancer. The dominant types of primary tumors are invasive ductal carcinoma with
      moderate histopathological grade. The rate of triple-negative breast carcinoma
      may be higher in occult breast cancer.

PMID- 21740835
TI  - Hemodynamic parameters obtained by transthoracic echocardiography and right heart
      catheterization: a comparative study in patients with pulmonary hypertension.
AB  - BACKGROUND: Hemodynamic evaluation is crucial for the management of patients with
      pulmonary hypertention. Clinicians often prefer a rapid and non-invasive method.
      This study aimed to examine the feasibility of transthoracic echocardiography for
      the measurements of hemodynamic parameters in patients with pulmonary
      hypertension. METHODS: A prospective single-center study was conducted among 42
      patients with pulmonary hypertension caused by different diseases. Transthoracic
      echocardiography and right-heart catheterization were performed within 24 hours.
      Pulmonary artery systolic, diastolic and mean pressure (PASP, PADP and PAMP),
      cardiac output (CO), and pulmonary capillary wedge pressure (PCWP) were measured
      by both methods. A linear correlation and a Bland-Altman analysis were performed
      to compare the two groups of hemodynamic parameters. RESULTS: A good correlation
      was found between invasive and non-invasive measurements for PASP (r = 0.96),
      PADP (r = 0.85), PAMP (r = 0.88), CO (r = 0.82), and PCWP (r = 0.81). Further
      agreement analysis done by the Bland-Altman method showed that bias and a 95%
      confidence interval for PASP, PADP, and CO were clinically acceptable while great
      discrepancies existed for PAMP and PCWP. CONCLUSIONS: The non-invasive
      measurements by PASP, PADP, and CO in patients with pulmonary hypertension
      correlate well with the invasive determinations. Transthoracic echocardiography
      (TTE) was inappropriate for estimating PCWP and PAMP.

PMID- 21740836
TI  - Optimal technique of three-dimensional MRI of the lumbar nerve root and its
      radicular vein in normal and lumbar disc herniation patients.
AB  - BACKGROUND: Although three-dimensional MRI (3D-MRI) of short T1 inversion
      recovery turbo spin-echo (STIR TSE) has showed superior to two-dimensional MRI
      (2D-MRI) in showing the spinal cord and lumbar nerve roots, it remains difficult
      in demonstrating radicular vein at present. We have found that short T1 inversion
      recovery long time echo (STIR LONG TE) was better in showing radicular vein. To
      further study the methods and character of the 3D-MRI of lumbar nerve root,
      ganglions and radicular vein in normal and lumbar disc herniation (LDH) adults,
      in the present study, we evaluated two 3D-MRI techniques, STIR TSE and STIR LONG
      TE for demonstrating lumbar nerve roots and especial radicular vein in normal and
      LDH adults. METHODS: Twelve normal adult persons and 19 LDH patients were
      included in this study; special oblique coronal location was adopted. STIR TSE
      and STIR LONG TE were performed in all participants, and the detection rates of
      radicular vein and nerve root of L3, L4, L5, S1 were calculated. The grading
      system was used in grading compromise of the intraspinal extradural lumbar nerve
      root, ganglion and radicular vein in LDH patients, and all the grading injury of
      nerve root, ganglion and radicular vein had been evaluated. RESULTS: The definite
      rate of radicular vein (DRRV) of 3D-MRI of STIR LONG TE was significantly
      different from that of STIR TSE. DRRV of STIR LONG TE was L3, 91.7%, L4, 100%,
      L5, 100%, S1, 100% and that of STIR TSE was L3, 33.3%, L4, 37.5%, L5, 58.3%, S1,
      45.8% in normal adults. It showed no difference between STIR LONG TE and STIR TSE
      in the detection rate of nerve root. The different patho-injuries of nerve root,
      ganglion and radicular vein could be seen in all LDH patients by the 3D-MRI of
      STIR LONG TE. The mean score of Japanese Orthopaedic Association (JOA) was 16.16,
      and 29 nerve roots were calculated in all the study. The mean grading injury of
      nerve root was 2.17, that of nerve root ganglion was 1.28, that of radicular vein
      was 1.83, and the mean co-grading injury of nerve root, ganglion and radicular
      vein was 5.31. The correlation coefficient was 0.478 (P = 0.010) between the
      score of JOA and that of radicular vein. CONCLUSION: The 3D-MRI of STIR LONG TE
      is superior to STIR TSE for not only detecting the lumbar nerve root, ganglion
      and especial radicular vein in normal adults, but also displaying their patho
      injuries degree in LDH patients.

PMID- 21740837
TI  - Nerve plane-sparing radical hysterectomy: a simplified technique of nerve-sparing
      radical hysterectomy for invasive cervical cancer.
AB  - BACKGROUND: In order to simplify the complicated procedure of nerve-sparing
      radical hysterectomy, a novel technique characterized by integral preservation of
      the autonomic nerve plane has been employed for invasive cervical cancer. The
      objective of this study was to introduce the nerve plane-sparing radical
      hysterectomy technique and compare its efficacy and safety with that of nerve
      sparing radical hysterectomy. METHODS: From September 2006 to August 2010, 73
      consecutive patients with International Federation of Gynecology and Obstetrics
      stage IB to IIA cervical cancer underwent radical hysterectomy with two different
      nerve-sparing approaches. Nerve-sparing radical hysterectomy was performed for
      the first 16 patients (nerve-sparing radical hysterectomy group). The detailed
      autonomic nerve structures were identified and separated by meticulous dissection
      during this procedure. After January 2008, the nerve plane-sparing radical
      hysterectomy procedure was developed and performed for the next 57 patients
      (nerve plane-sparing radical hysterectomy group). During this modified procedure,
      the nerve plane (meso-ureter and its extension) containing most of the autonomic
      nerve structures was integrally preserved. The patients' clinicopathologic
      characteristics, surgical parameters, and outcomes of postoperative bladder
      function were compared between the two groups. RESULTS: There were no significant
      differences between the nerve plane-sparing radical hysterectomy and nerve
      sparing radical hysterectomy groups regarding age, International Federation of
      Gynecology and Obstetrics stage, pathological type, preoperative treatment, or
      need for intraoperative blood transfusion. The nerve plane-sparing radical
      hysterectomy group had a higher body mass index than that of the nerve-sparing
      radical hysterectomy group (P = 0.028). The mean surgical duration in the nerve
      plane-sparing radical hysterectomy and nerve-sparing radical hysterectomy groups
      were (262 +/- 46) minutes and (341 +/- 36) minutes (P < 0.01). On the 8th
      postoperative day, 41 (71.9%) patients in the nerve plane-sparing radical
      hysterectomy group and nine (56.3%) patients in the nerve-sparing radical
      hysterectomy group had a postvoid residual urine volume of < 100 ml (P = 0.233).
      The median duration of catheterization was eight days (range 8 - 23 days) for the
      nerve plane-sparing radical hysterectomy group and eight days (range 8 - 22 days)
      for the nerve-sparing radical hysterectomy group (P = 0.509). Neither surgery
      related injury nor pathologically positive margins were reported in either group.
      CONCLUSION: Nerve plane-sparing radical hysterectomy is a reproducible and
      simplified modification of nerve-sparing radical hysterectomy, and may be
      preferable to nerve-sparing radical hysterectomy for treatment of early-stage
      invasive cervical cancer.

PMID- 21740838
TI  - Down-regulation of human leukocyte antigens class I on peripheral T lymphocytes
      and NK cells from subjects in region of high-incidence gastrointestinal tumor.
AB  - BACKGROUND: Many types of human tumors can suppress the immune system to enhance
      their survival. Loss or down-regulation of human leukocyte antigens (HLA) class I
      on tumors is considered to be a major mechanism of tumor immune escape. Our
      previous studies found that HLA class I on peripheral-blood mononuclear cells was
      significantly lower in gastric cancer patients. The present study made an
      analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells
      from subjects of Lijiadian village, a village with high-incidence
      gastrointestinal tumor. METHODS: A total of 181 villagers from Lijiadian village
      and 153 normal controls from the Department of Health Examination Center were
      enrolled in this study. Using a multi-tumor markers detection system, these
      villagers were divided into two groups: high-risk group (tumor markers positive
      group) and low-risk group (tumor markers negative group). The percentage of T
      lymphocytes and NK cells and levels of HLA class I on their surface were
      determined in these subjects by flow cytometry. RESULTS: Percentages of T
      lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with
      age. The expression level of HLA class I on peripheral T lymphocytes and NK cells
      was not affected by age or gender, but was significantly down-regulated in
      Lijiadian villagers (P < 0.05), especially on the surface of NK cells (P < 0.01).
      Compared with the low-risk group, there was a significant reduction of HLA class
      I on peripheral T lymphocytes (P < 0.05) and NK cells (P < 0.05) in the high-risk
      group. CONCLUSIONS: HLA class I on peripheral T lymphocytes and NK cells may be
      involved in tumorigenesis and development of gastrointestinal tumor, and
      understanding their changes in expression may provide new insights into the
      mechanism of tumor immunity.

PMID- 21740839
TI  - First 30 endobronchial ultrasound-guided transbronchial needle aspirations: a
      single institution's early experience.
AB  - BACKGROUND: A new technique developed in 2002, real time endobronchial ultrasound
      guided transbronchial needle aspiration (EBUS-TBNA), has been one of the most
      important tools in lymph nodes (LNs) staging before lung cancer surgery. EBUS
      TBNA was introduced into China in 2008. METHODS: Between June 2009 and October
      2009, 30 patients with mediastinal/hilar lymphadenopathy and thoracic masses
      previously detected with CT scan underwent EBUS-TBNA without rapid onsite
      cytological examination. RESULTS: From 30 patients, 33 samples were obtained from
      LNs and seven samples from intrapulmonary lesions. Twenty out of the 23 lung
      cancer diagnoses were clarified through the procedure, with sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy
      being 87%, 100%, 100%, 70% and 90%, respectively. All three false negative cases
      were found in the first five procedures. Additionally, among the 33 LNs examined,
      three specimens that had no lymphocytes were also found within the first five
      procedures. There were no major complications, and the procedures were
      uneventful. CONCLUSIONS: EBUS-TBNA seems a safe and effective technique in making
      diagnosis for mediastinal/hilar LNs and intrapulmonary masses. For pulmonologists
      experienced in bronchoscopy, the sensitivity of the procedure for diagnosing lung
      cancer should be no less than 90% after the initial five procedures.

PMID- 21740840
TI  - Evaluation of renal artery stenosis using color Doppler sonography in young
      patients with multiple renal arteries.
AB  - BACKGROUND: Some individuals have multiple renal arteries. Severe stenosis in one
      of the arteries may cause refractory hypertension. The detection of stenosis
      within one of the multiple renal arteries usually required invasive procedures,
      such as computed tomographic angiography (CTA) and magnetic resonance angiography
      (MRA). This study reported the application of color Doppler sonography (CDS) in
      the detection of severe stenosis in one of the multiple arteries. METHODS:
      Patients with multiple renal arteries and one of the arteries with severe
      stenosis were retrospectively studied. Peak systolic velocities (PSV) of renal
      arteries and the intrarenal CDS patterns were collected and compared. The
      diagnosis was confirmed by digital subtraction angiography (DSA). RESULTS: Four
      children with multiple renal arteries and one of the arteries with stenosis were
      investigated. They were admitted due to refractory hypertension. CDS screening
      identified two renal arteries in one kidney of each patient with one of the two
      renal arteries having stenosis > 70%. The PSV of the stenosed arteries were much
      higher, and the intrarenal CDS patterns supplied by the stenosed arteries changed
      into T-P patterns. CONCLUSION: Non-invasive CDS technology may be a useful method
      to identify severe stenosis in one of multiple renal arteries in young patients.

PMID- 21740841
TI  - Effects of age on ocular anterior segment dimensions measured by optical
      coherence tomography.
AB  - BACKGROUND: Older subjects tend to have smaller ocular anterior segment. The
      present study aimed to measure anterior segment dimensions with optical coherence
      tomography (OCT) and quantitatively assess the effect of age and other factors.
      METHODS: Anterior segment OCT images were obtained in normal subjects residing in
      the greater Los Angeles area. Four line scans were acquired at the 90 degrees ,
      45 degrees , 0 degrees  and 135 degrees  meridians of each eye. Computer calipers
      acquired anterior segment dimensions of corneal diameter, anterior chamber width,
      corneal vault and anterior chamber depth on OCT images. Measurements from 4
      meridians were averaged. Axial length and corneal power were measured by partial
      coherence interferometry. Univariate and multivariate analyses were performed to
      assess correlations. RESULTS: Sixty-six eyes of 33 normal subjects (aged 22 - 65
      years, 19 Asians, 14 Caucasians) were enrolled. For every 1 year of age, corneal
      diameter was 0.033 mm narrower (P < 0.01), anterior chamber width was 0.031 mm
      narrower (P < 0.01), corneal vault was 0.016 mm lower (P < 0.01), and anterior
      chamber depth was 0.025 mm lower (P < 0.01). Asian eyes had smaller corneal
      diameter (P = 0.035) and anterior chamber width (P = 0.015) compared with those
      of Caucasian eyes. Body height showed positive correlation with corneal diameter
      (0.039 mm per centimeter of height, P < 0.01) and corneal vault (0.024 mm per
      centimetre of height, P < 0.01). Gender did not have an independent effect on
      anterior segment dimensions. CONCLUSIONS: Anterior segment dimensions were
      smaller in older subjects. Age-related changes may affect the tolerability of
      long-term implants such as phakic intraocular lens.

PMID- 21740842
TI  - A new mutation in the thyroid hormone receptor gene of a Chinese family with
      resistance to thyroid hormone.
AB  - BACKGROUND: Resistance to thyroid hormone (RTH) is a dominant inherited syndrome
      of reduced tissue responsiveness to thyroid hormone. It is usually due to
      mutations located at the ligand-binding domain and adjacent hinge region of the
      thyroid hormone receptor beta (TRbeta). We report the clinical and laboratory
      characteristics and the genetic analysis of a patient with this rare disorder and
      his family members. METHODS: The clinical presentations and changes of thyroid
      function tests (TFTs) including magnetic resonance imaging (MRI) of pituitary and
      other laboratory tests were analysed. TFTs of his family's members were detected
      as well. Direct DNA sequencing of the TRbeta gene was done for those with
      abnormal TFTs. RESULTS: The RTH child had goiter, irritability, aggressiveness,
      and sudoresis. His TFTs showed high levels of circulating free thyroid hormones
      (FT(4) and FT(3)) and normal thyroid-stimulating hormone (TSH) concentrations. He
      felt worse when treated as hyperthyroidism (Grave disease) with thiamazole and
      his clinical presentations got improved obviously when treated as RTH with
      bromocriptine without obvious advert effect. We identified a novel missense
      mutation, A317D, located in exon 9 of the gene of this boy and his mother. His
      mother had not any clinical presentation, but having abnormal TFTs results.
      CONCLUSIONS: This patient reported here was concordant with the criteria of RTH.
      The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel
      mutation was found in the TRbeta, A317D, of this family. This research verified
      the phenomena that there is a clinical heterogeneity within the same mutation of
      different RTH patients.

PMID- 21740843
TI  - Effect of probucol on vascular remodeling due to atherosclerosis in rabbits: an
      intravascular ultrasound study.
AB  - BACKGROUND: Probucol is known to reduce the development of atherosclerotic
      lesions, but its impact on vascular remodeling associated with de novo
      atherosclerosis is incompletely understood. We therefore examined the effect of
      probucol on vascular remodeling in a rabbit model of established atherosclerosis.
      METHODS: Aortic atherosclerosis was induced by a combination of endothelial
      injury and 10 weeks' atherogenic diet. Animals were then randomized to receive
      the foregoing diet without or with 1% (wt/wt) probucol for 16 weeks. At the end
      of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical
      and gene expression studies were performed. RESULTS: Probucol significantly
      decreased vessel cross-sectional area, plaque area and plaque burden without
      effect on lumen area. More negative remodeling and less positive remodeling
      occurred in the abdominal aortas of probucol group than the control group (56%
      vs. 21%, 18% vs. 54%, respectively, both P < 0.01). In addition, the probucol
      group showed a smaller mean remodeling index relative to the control group (0.93
      +/- 0.13 vs. 1.05 +/- 0.16, P < 0.01). Furthermore, probucol treatment decreased
      macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced
      the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S
      (all P < 0.01). CONCLUSIONS: These findings suggest that probucol may attenuate
      the enlargement of atherosclerotic vessel walls and be associated with a negative
      remodeling pattern without affecting the lumen size. This effect may involve
      inhibition of extracellular matrix degradation and prevention of apoptosis in
      atherosclerotic plaques.

PMID- 21740844
TI  - Detection of neural stem cells function in rats with traumatic brain injury by
      manganese-enhanced magnetic resonance imaging.
AB  - BACKGROUND: Previously we had successfully tracked adult human neural stem cells
      (NSCs) labeled with superparamagnetic iron oxide particles (SPIOs) in host human
      brain after transplantation in vivo non-invasively by magnetic resonance imaging
      (MRI). However, the function of the transplanted NSCs could not be evaluated by
      the method. In the study, we applied manganese-enhanced MRI (ME-MRI) to detect
      NSCs function after implantation in brain of rats with traumatic brain injury
      (TBI) in vivo. METHODS: Totally 40 TBI rats were randomly divided into 4 groups
      with 10 rats in each group. In group 1, the TBI rats did not receive NSCs
      transplantation. MnCl2.4H2O was intravenously injected, hyperosmolar mannitol was
      delivered to disrupt rightside blood brain barrier, and its contralateral forepaw
      was electrically stimulated. In group 2, the TBI rats received NSCs (labeled with
      SPIO) transplantation, and the ME-MRI procedure was same to group 1. In group 3,
      the TBI rats received NSCs (labeled with SPIO) transplantation, and the ME-MRI
      procedure was same to group 1, but diltiazem was introduced during the electrical
      stimulation period. In group 4, the TBI rats received phosphate buffered saline
      (PBS) injection, and the ME-MRI procedure was same to group 1. RESULTS:
      Hyperintense signals were detected by ME-MRI in the cortex areas associated with
      somatosensory in TBI rats of group 2. These signals, which could not be induced
      in TBI rats of groups 1 and 4, disappeared when diltiazem was introduced in TBI
      rats of group 3. CONCLUSION: In this initial study, we mapped implanted NSCs
      activity and its functional participation within local brain area in TBI rats by
      ME-MRI technique, paving the way for further pre-clinical research.

PMID- 21740845
TI  - Therapeutic effects of signal transducer and activator of transcription 3 siRNA
      on human breast cancer in xenograft mice.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is usually
      constitutively activated in a variety of malignancies. It directly contributes to
      tumorigenesis, invasion, and metastasis. The surgical treatment of breast cancer
      has made no breakthroughs in terms of treatment effect, in spite of its long
      history. Current biotherapies bring a note of optimism to breast cancer
      treatment. To explore the possibility of a siRNA targeted STAT3 blocking
      treatment for over-activated tumor cells, we evaluated the efficacy of a STAT3
      siRNA on human breast cancer cells in vitro and in vivo. METHODS: Three MCF-7
      human breast cancer cell lines were tested: control MCF-7 cells, non-specific
      siRNA transfected MCF-7 cells and STAT3 siRNA transfected MCF-7 cells. Expression
      of STAT3 in MCF-7 cells was inhibited by RNA interference (RNAi). The STAT3 mRNA
      and protein levels were detected by semi-quantity RT-PCR and Western blotting.
      Cell proliferation and apoptosis were determined by MTT method and flow
      cytometry. The three groups of MCF-7 cells mentioned above were transplanted
      subcutanuously into nude mice and their tumorgenic ability observed. The STAT3
      mRNA and protein levels of the samples from tumors in different groups were
      determined by semi-quantity RT-PCR and Western blotting and compared. RESULTS: In
      STAT3 siRNA transfected MCF-7 cells, the expressions (STAT3/beta-actin) of STAT3
      mRNA (0.327 +/- 0.020) and protein (0.153 +/- 0.006) were significantly lower
      than that in control MCF-7 cells (mRNA 1.093 +/- 0.018, protein 1.374 +/- 0.022)
      and non-specific siRNA transfected MCF-7 cells (mRNA 1.035 +/- 0.050, protein
      1.320 +/- 0.033) (P < 0.05). MTT showed that cell proliferation was significantly
      reduced and the cell growth inhibition ratio in the STAT3-siRNA group was (44.00
      +/- 5.10)%, significantly higher than that in non-specific siRNA transfected MCF
      7 cells ((16.10 +/- 1.05)%, P < 0.05). Flow cytometry results showed that more
      apoptosis was observed in the STAT3-siRNA group. The rate of apoptosis was (14.79
      +/- 0.22)%, much higher than in control MCF-7 cells (7.06 +/- 0.71) and non
      specific siRNA transfected MCF-7 cells (8.45 +/- 0.43) (P < 0.05). The tumor
      growth in the STAT3 siRNA transfected MCF-7 cells was significantly slower than
      in the two control groups. On the 22th day after transplantation the tumor weight
      ((21.40 +/- 10.57) mg) and volume ((41.15 +/- 12.17) mm(3)) in the STAT3 siRNA
      transfected group were significantly lower than in control group (weight (88.60
      +/- 12.16) mg, volume (118.45 +/- 24.68) mm(3)) and non-specific siRNA
      transfected group (weight (57.20 +/- 21.86) mg, volume (101.36 +/- 21.90) mm(3))
      (P < 0.05). Both the STAT3 mRNA and protein levels in the tumors from the STAT3
      siRNA transfected group were significantly lower than in the tumors from the two
      control groups. CONCLUSIONS: STAT3 siRNA can effectively silence the STAT3 gene
      in vitro and in vivo, increase cell apoptosis rate and significantly decrease
      cell proliferation, which inhibits the growth of breast cancer cell in vitro.
      Tumor growth of xenograft mice is significantly inhibited. The results obtained
      in vivo are in consistency with those in vitro. STAT3 may be a novel therapeutic
      target for breast cancer and RNA interference has potential clinical application.

PMID- 21740846
TI  - Optimization of transfection efficiency of small interfering RNA in purified
      human prolactinoma cells.
AB  - BACKGROUND: Control of hypersecretion of certain hormones is one of the key
      targets in the treatment of pituitary adenomas. RNA interference has been shown
      to inhibit protein expression, and thus it may represent a promising method for
      the treatment of pituitary adenomas. In the present study, transfection
      efficiency of small interfering RNA (siRNA) was optimized in human prolactinoma
      cells. METHODS: First, a method was optimized to extract highly purified human
      prolactinoma cells in vitro. The extracted cells were verified to retain the
      physiological features of prolactin (PRL) secretion. Second, three conditions for
      siRNA transfection were tested by the evaluation of transfection efficiency and
      cell viability. The proper transfection condition was verified for human
      prolactinoma cells. Third, the siRNA for prolactin was transfected into the human
      prolactinoma cells, and the suppression of PRL mRNA was evaluated by quantitative
      real-time reverse transcription-PCR. RESULTS: The siRNA of 100 pmol with
      Lipofectamine 2000 of 5 ul for 1 * 10(6) cells was proved preferable, with
      transfection efficiency being 53.3% and cell viability being 69.7%. In the
      preliminary experiment the siRNA against PRL decreased the mRNA of PRL by 34.0%.
      CONCLUSION: It is possible to inhibit hormone hypersecretion by RNA interference,
      that may eventually enable therapeutic siRNA drugs developed.

PMID- 21740847
TI  - Beneficial effects of metformin on primary cardiomyocytes via activation of
      adenosine monophosphate-activated protein kinase.
AB  - BACKGROUND: Metformin has become a cornerstone in the treatment of patients with
      type-2 diabetes. Accumulated evidence suggests that metformin supports direct
      cardiovascular effects. The present study aimed to investigate if metformin has
      beneficial effects on primary cardiomyocytes damaged by H2O2, and reveal the
      potential mechanism of action of metformin. METHODS: Cardiomyocytes were
      incubated in the presence of 100 umol/L H2O2 for 12 hours. Cardiomyocytes were
      pretreated with metformin at different concentrations and time and with
      aminoimidazole carboxamide ribonucleotide (AICAR) (500 umol/L), an adenosine
      monophophate (AMP)-activated protein kinase (AMPK) agonist for 60 minutes before
      the addition of H2O2. Other cells were preincubated with compound C (an AMPK
      antagonist, 20 umol/L) for 4 hours. The viability and apoptosis of cells were
      analyzed. AMPK, endothelial nitric oxide synthase (eNOS), and transforming growth
      factor (TGF)-beta1 were analyzed using immunblotting. RESULTS: Metformin had
      antagonistic effects on the influences of H2O2 on cell viability and attenuated
      oxidative stress-induced apoptosis. Metformin also increased phosphorylation of
      AMPK and eNOS, and reduced the expression of TGF-beta1, basic fibroblast growth
      factor (bFGF), and tumor necrosis factor (TNF)-alpha. CONCLUSIONS: Metformin has
      beneficial effects on cardiomyocytes, and this effect involves activation of the
      AMPK-eNOS pathway. Metformin may be potentially beneficial for the treatment of
      heart disease.

PMID- 21740848
TI  - Generation of trans-arachidonic acid under nitrative stress is associated with
      upregulation of thromponsdin-1 in diabetic rats.
AB  - BACKGROUND: Trans-arachidonic acids (TAAs), newly discovered markers of nitrative
      stress and the major products of nitrogen dioxide (NO2(.))-mediated isomerization
      of arachidonic acid (AA), represent a new mechanism of NO2(.)-induced toxicity.
      It has been reported that TAAs were generated in oxygen-induced microvascular
      degeneration model and TAAs were also generated in a diabetic retinopathy (DR)
      model. In this study, we examined high glucose-induced nitrative stress damage
      and TAAs levels and explored the possible mechanisms for DR caused by reactive
      nitrogen species. METHODS: Diabetic rats were induced by intraperitoneal
      injection of streptozotocin (STZ) at 60 mg/kg. Bovine retinal capillary
      endothelial cells (BRECs) were selectively cultured and incubated with normal or
      high glucose. The serum TAAs and AA in diabetic rats were measured by the gas
      chromatography and mass spectrometry (GC/MS) method. The ratio of peak area of
      TAAs to AA with selected ion of 79 was estimated by a group t-test.
      Thrombospondin-1 (TSP-1) in the rat retinas and BRECs extracts were examined by
      Western blotting. The phosphorylation of extracellular signal-regulated kinase
      1/2 (ERK1/2) protein was examined by Western blotting in BRECs incubated with
      high glucose. RESULTS: The TAAs to AA ratio (TAAs/AA) was significantly increased
      in the serum at 8, 12 and 16 weeks after STZ injection (P < 0.05), with no
      noticeable change found at 2 or 4 weeks (P > 0.05). Expression of TSP-1 in the
      retina of diabetic rats was progressively elevated according to the duration of
      diabetes. TSP-1 expression was increased in BRECs incubated with high glucose at
      48 hours. Moreover, high glucose also increased ERK1/2 expression, which peaked
      at 30 minutes and then decreased in the following 48 hours. CONCLUSION: An
      elevation of TAAs/AA is associated with high glucose-induced nitrative stress,
      which probably involves upregulation of TSP-1 through activating ERK1/2.

PMID- 21740849
TI  - Heterosexual risk of HIV infection in China: systematic review and meta-analysis.
AB  - BACKGROUND: Heterosexual sex has become the dominant transmission route in China.
      Recently studies reported high heterogeneity in heterosexual transmission risk in
      resource-limited countries. The aim of this study was to summarize the risk of
      HIV transmission among Chinese serodiscordant couples. METHODS: A systematic
      review and meta-analysis of observational studies of heterosexual HIV
      transmission among serodiscordant couples in China was conducted. Two reviewers
      conducted a literature search using the China National Knowledge Infrastructure
      (CNKI), Chinese Medical Current Contents (CMCC), and Medline databases. Pooled
      transmission estimates per 100 person-years (PY) were calculated using a random
      effects model. Meta-regression analysis and subgroup analysis stratified by study
      design, transmission direction and period of antiretroviral therapy (ART)
      availability were conducted to assess the factors associated with transmission.
      RESULTS: Eleven eligible studies were identified reporting on 11 984 couples and
      405 HIV transmission events. HIV transmission risk from HIV-positive individuals
      to heterosexual partners was 1.68 (95%CI 0.74 - 2.62) per 100 PY. Study design
      did not reach statistical significance in meta-regression analysis. The pooled
      female-to-male transmission estimate was 1.11 (95%CI 0.09 - 2.14) per 100 PY and
      male-to-female transmission estimate was 1.43 (95%CI 0.19 - 2.68) per 100 PY. The
      pooled estimate for those before the availability of the Chinese National Free
      Antiretroviral Therapy Program (2.13 (95%CI 0.00 - 4.63) per 100 PY) was higher
      than that for those after the implementation of this program (1.44 (95%CI 0.62 -
      2.26) per 100 PY). CONCLUSIONS: Transmission estimates in China were lower than
      other developing countries, but higher than developed countries. Research that
      better defines HIV secondary transmission rates and the associated behavioral,
      treatment adherence, and health-related risk factors among heterosexual
      serodiscordant couples in China is needed.

PMID- 21740850
TI  - Induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells are a recent development which has brought a
      promise of great therapeutic values. The previous technique of somatic cell
      nuclear transfer (SCNT) has been ineffective in humans. Recent discoveries show
      that human fibroblasts can be reprogrammed by a transient over expression of a
      small number of genes; they can undergo induced pluripotency. iPS were first
      produced in 2006. By 2008, work was underway to remove the potential oncogenes
      from their structure. In 2009, protein iPS (piPS) cells were discovered. Surface
      markers and reporter genes play an important role in stem cell research. Clinical
      applications include generation of self renewing stem cells, tissue replacement
      and many more. Stem cell therapy has the ability to dramatically change the
      treatment of human diseases.

PMID- 21740851
TI  - Sulfur dioxide acts as a novel endogenous gaseous signaling molecule in the
      cardiovascular system.
AB  - OBJECTIVE: Sulfur dioxide was considered to be toxic and detrimental to human
      health. However, this review highlights recent advances that suggest sulfur
      dioxide might be a novel endogenous gaseous signaling molecule involved in the
      regulation of cardiovascular functions. DATA SOURCES: The data used in this
      review were mainly from the studies reported in Medline and PubMed published from
      1986 to 2010. STUDY SELECTION: Original articles and critical reviews selected
      were relevant to exogenous and endogenous sulfur dioxide. RESULTS: The sulfur
      dioxide/aspartate amino transferase pathway is endogenously generated in the
      cardiovascular system, and sulfur dioxide shows broad bioactive effects, such as
      antihypertension, vasodilation, and amelioration of vascular remodeling. A
      disturbed sulfur dioxide/aspartate amino transferase pathway is known to be
      involved in the pathogenesis of many cardiovascular diseases, such as ischemia
      reperfusion injury, monocrotaline-induced pulmonary hypertension, athrosclerosis,
      spontaneous hypertension and hypoxic pulmonary hypertension. Furthermore, in
      experimental studies the prognosis of these cardiovascular diseases can be
      improved by targeting endogenous sulfur dioxide. CONCLUSION: The findings suggest
      that sulfur dioxide is a novel endogenous gaseous signaling molecule involved in
      the regulation of cardiovascular functions.

PMID- 21740852
TI  - Magnetic resonance imaging in assessment of treatment response of gamma knife for
      brain tumors.
AB  - OBJECTIVE: To review the applications of magnetic resonance imaging (MRI)
      techniques in assessing treatment response to gamma knife radiosurgery for brain
      tumors. DATA SOURCES: Published articles about assessing treatment response to
      gamma knife radiosurgery for brain tumors were selected using PubMed. The search
      terms were "MRI", "gamma knife" and "brain tumors". STUDY SELECTION: Articles
      regarding the MRI techniques using for early assessment of treatment response of
      gamma knife were selected. RESULTS: MRI techniques, especially diffusion weighted
      imaging, perfusion weighted imaging, magnetic resonance spectroscopy, are useful
      for early assessment of treatment response of gamma knife by detecting the
      hemodynamic, metabolic, and cellular alterations. Moreover, they can also provide
      important information on prognosis. CONCLUSIONS: Diffusion weighted imaging,
      perfusion weighted imaging and magnetic resonance spectroscopy can provide early
      assessment of treatment response of gamma knife for brain tumors, and also
      information of tumor progression or recurrence earlier than conventional MRI. But
      there are still many questions to be answered which should be based on the
      development and advancement of MRI and related disciplines.

PMID- 21740853
TI  - Near-fatal infection following an elective ankle-fracture fixation: less risk
      should not mean less vigilance.
AB  - Surgical fixation of closed ankle fracture is traditionally viewed as having low
      risk for post-operative infection. Only a few cases of surgical-site confined
      infection have been reported. Because of the low infection risk, the necessity
      for perioperative prophylaxis has been questioned. We report a case of fulminant
      methicillin-resistant Staphylococcus aureus endocarditis occurring shortly after
      an elective ankle fixation surgery in an elderly woman with chronic rheumatoid
      arthritis. Because systemic infection was unexpected, she had been given
      antipyretics for postoperative fever until just before rapid clinical
      deterioration. A nearly fatal hematogenous infection occurred after such a
      procedure, indicating the necessity for being on high alert and considering the
      possibility of bloodstream infection.

PMID- 21740854
TI  - Hypersensitivity pneumonitis due to residential mosquito-coil smoke exposure.
AB  - We reported a previously healthy 25-year-old female patient who developed
      hypersensitivity pneumonitis following repeated exposures to the smoke of
      mosquito coils. The patient presented with vague symptoms of cough and fever for
      3 days. Diagnostic criteria proposed for clinical use in this case included
      history, exposure to a recognized antigen, physical examination, consistent
      radiographic images, bronchoalveolar lavage and lung biopsy. Much symptomatic
      relief and better radiographic response were noted after short-term use of oral
      corticosteroid and removal of the offending antigen.

PMID- 21740855
TI  - Hemorrhoid sclerotherapy with the complication of abdominal compartment syndrome:
      report of a case.
AB  - The complications of injection sclerotherapy for hemorrhoid are always local.
      Herein, we report a case in which a female patient with abdominal compartment
      syndrome developed after receiving a local injection of a sclerosing agent for
      hemorrhoid.

PMID- 21740856
TI  - Variables influencing the likelihood of cardiac dysrhythmias during
      extracorporeal shock wave lithotripsy.
AB  - INTRODUCTION: Extracorporeal shock wave lithotripsy (ESWL) is a safe and
      effective treatment of upper urinary tract calculi. While serious side effects
      are rare, transient cardiac dysrhythmias (CD) may be associated with ESWL. The
      exact etiology of these events, which are often unpredictable, is poorly
      understood. Awareness of CD during ESWL and identification of risk factors for
      developing them could help clinicians predict and manage them safely and
      effectively. The current study examines selected variables to determine whether
      they may predispose individuals to developing CD during ESWL. METHODS: We
      compared 16 patients who experienced CD during ESWL to 56 control patients. Cases
      and controls were compared with respect to several continuous and discrete
      variables, including age, pre-treatment heart rate, number of shocks received
      during treatment, energy setting of the lithotripter, gender, presence of a
      ureteric stent, previous ESWL and side being treated. RESULTS: Cardiac
      dysrhythmias occurred more frequently in younger patients and in those being
      treated for right-sided stones. The other variables did not influence the
      likelihood of CD. All CD resolved promptly following conversion to
      electrocardiogram (ECG)-gating. CONCLUSION: Younger age and right-sided treatment
      predisposed individuals to developing CD during ESWL. Careful ECG monitoring
      should be performed during treatment.

PMID- 21740859
TI  - The beam divergence of an indium LMIS at a distance of 50 MUm as determined by
      plasma diagnostic measurements.
AB  - The current-dependent beam divergence at a distance of 50 MUm from an indium
      liquid metal ion source is derived from experimental data obtained by measuring
      the beam spread with a 3D Plasma diagnostic system at a distance of 10 cm from
      the needle tip. The observed relationship between emission current and beam
      divergence in vicinity of the emitting needle is used to design a focusing
      electrode for a field-emission electric propulsion thruster operating at currents
      up to 150 MUA. Another application involves focused ion beam columns which may
      choose to forego a beam-limiting aperture, such as LMIS-based rapid machining
      tools with large beam currents.

PMID- 21740860
TI  - Optimized hand fabricated AFM probes for simultaneous topographical and
      electrochemical tapping mode imaging.
AB  - In this work hybrid AFM-electrochemical (SECM) probes to be used in dynamic
      atomic force microscopy are presented. These nanosensors are hand fabricated from
      gold microwires using a simple benchtop method. They display proportions close to
      commercially available silicon and silicon nitride cantilevers giving comparable
      performance in terms of resolution and imaging stability. The remarkable
      characteristic of these hybrid nanosensors is that they allow the coupling of 3D
      imaging ability and versatility of atomic force microscopy with the power of
      electrochemical methods. Local measurement of electrochemical-activity of a test
      sample consisting of gold bands functionalized by redox-labeled nanometer-sized
      polyethylene glycol chains has been achieved with simultaneous imaging of the 3D
      surface topography at high resolution. These hybrid AFM-SECM tips are capable of
      sensing local electrochemical currents down to ~ 10 fA emphasizing the
      sensitivity and resolution of this technique.

PMID- 21740861
TI  - Simulation of ion imaging: sputtering, contrast, noise.
AB  - Scanning ion microscopy has received a boost in the last decade, thanks to the
      development of novel ion sources employing light ions, like He(+), or ions from
      inert gases, like Ne(+) and Ar(+). Scanning ion images, however, might not be as
      easy to interpret as SEM micrographs. The contrast mechanisms are different, and
      there is always a certain degree of sample sputtering. The latter effect, on the
      one hand, prevents assessing the resolution on the basis of a single image, and,
      on the other hand, limits the probing time and thus the signal-to-noise ratio
      that can be obtained. In order to fully simulate what happens when energetic ions
      impact on a sample, a Monte Carlo approach is often used. In this paper, a
      different approach is proposed. The contrast is simulated using curves of
      secondary electron yields versus the incidence angle of the beam, while the
      surface modification prediction is based on similar curves for the sputtering
      yield. Finally, Poisson noise from primary ions and secondary electrons is added
      to the image. It is shown that the evaluation of an ion imaging tool cannot be
      condensed in a single number, like the spot size or the edge steepness, but must
      be based on a more complex analysis taking into account at least three
      parameters: sputtering, contrast and signal-to-noise ratio. It is also pointed
      out that noise contributions from the detector cannot be neglected for they can
      actually be the limiting factor in imaging with focused ion beams. While
      providing already good agreement with experimental data in some imaging aspects,
      the proposed approach is highly modular. Further effects, like edge enhancement
      and detection, can be added separately.

PMID- 21740862
TI  - Evaluation of two-dimensional strain distribution by STEM/NBD.
AB  - We proposed a strain mapping technique by Nano Beam electron Diffraction (NBD)
      combined with an energy filter (EF) and a scanning transmission electron
      microscopy (STEM) function. The STEM function improves the accuracy of a position
      where a diffraction pattern is acquired. The EF excludes inelastic scattering and
      enables novel numerical processing for the appropriate measurement of distances
      between diffraction disks. Using this technique, strain distributions were
      measured for two different types of p-MOSFETs, i.e., source/drain regions of each
      MOSFET is composed of different types of silicide, and the difference of their
      strain distributions in the channel region was confirmed. The proposed method was
      able to clarify that the strain distributions are quite different depending on
      the silicide materials even if the exterior of the MOSFETs was almost identical.

PMID- 21740863
TI  - Scanning transmission electron microscopy imaging dynamics at low accelerating
      voltages.
AB  - Motivated by the desire to minimize specimen damage in beam sensitive specimens,
      there has been a recent push toward using relatively low accelerating voltages
      (<100 kV) in scanning transmission electron microscopy. To complement
      experimental efforts on this front, this paper seeks to explore the variations
      with accelerating voltage of the imaging dynamics, both of the channelling of the
      fast electron and of the inelastic interactions. High-angle annular-dark field,
      electron energy loss spectroscopic imaging and annular bright field imaging are
      all considered.

PMID- 21740864
TI  - Imaging with low-voltage scanning transmission electron microscopy: a
      quantitative analysis.
AB  - A dedicated specimen holder has been designed to perform low-voltage scanning
      transmission electron microscopy in dark field mode. Different test samples,
      namely InGaAs/GaAs quantum wells, InGaAs nanowires and thick InGaAs layers, have
      been analysed to test the reliability of the model based on the proportionality
      to the specimen mass-thickness, generally used for image intensity interpretation
      of scattering contrast processes. We found that size of the probe, absorption and
      channelling must be taken into account to give a quantitative interpretation of
      image intensity. We develop a simple procedure to evaluate the probe-size effect
      and to obtain a quantitative indication of the absorption coefficient. Possible
      artefacts induced by channelling are pointed out. With the developed procedure,
      the low voltage approach can be successfully applied for quantitative
      compositional analysis. The method is then applied to the estimation of the In
      content in the core of InGaAs/GaAs core-shell nanowires.

PMID- 21740865
TI  - A fast algorithm for computing and correcting the CTF for tilted, thick specimens
      in TEM.
AB  - Today, the resolution in phase-contrast cryo-electron tomography is for a
      significant part limited by the contrast transfer function (CTF) of the
      microscope. The CTF is a function of defocus and thus varies spatially as a
      result of the tilting of the specimen and the finite specimen thickness. Models
      that include spatial dependencies have not been adopted in daily practice because
      of their high computational complexity. Here we present an algorithm which
      reduces the processing time for computing the 'tilted' CTF by more than a factor
      100. Our implementation of the full 3D CTF has a processing time on the order of
      a Radon transform of a full tilt-series. We derive and validate an expression for
      the damping envelope function describing the loss of resolution due to specimen
      thickness. Using simulations we quantify the effects of specimen thickness on the
      accuracy of various forward models. We study the influence of spatially varying
      CTF correction and subsequent tomographic reconstruction by simulation and
      present a new approach for space-variant phase-flipping. We show that our CTF
      correction strategies are successful in increasing the resolution after
      tomographic reconstruction.

PMID- 21740866
TI  - Assessment of waveguiding properties of gallium oxide nanostructures by angle
      resolved cathodoluminescence in a scanning electron microscope.
AB  - Cathodoluminescence (CL) of Ga(2)O(3) nanowires and planar microstructures has
      been studied in a scanning electron microscope, as a function of the orientation
      angle of the structures relative to the position of the light detection system in
      the microscope chamber. CL contrast shows a marked dependence on the detection
      angle due to the waveguiding behaviour of the structures. The angle resolved
      cathodoluminescence (ARCL) measurements enable to evaluate the optical losses of
      guided blue-ultraviolet light in nanowires with diameters in the sub-wavelength
      range, deposited on graphite tape or silicon. In planar, branched feather-like
      microstructures, ARCL images demonstrate the directional-dependent light guiding
      behaviour of the nano-branches.

PMID- 21740867
TI  - Defocus and twofold astigmatism correction in HAADF-STEM.
AB  - A new simultaneous autofocus and twofold astigmatism correction method is
      proposed for High Angle Annular Dark Field Scanning Transmission Electron
      Microscopy (HAADF-STEM). The method makes use of a modification of image
      variance, which has already been used before as an image quality measure for
      different types of microscopy, but its use is often justified on heuristic
      grounds. In this paper we show numerically that the variance reaches its maximum
      at Scherzer defocus and zero astigmatism. In order to find this maximum a
      simultaneous optimization of three parameters (focus, x- and y-stigmators) is
      necessary. This is implemented and tested on a FEI Tecnai F20. It successfully
      finds the optimal defocus and astigmatism with time and accuracy, compared to a
      human operator.

PMID- 21740868
TI  - Atomic force microscopy-based antibody recognition imaging of proteins in the
      pathological deposits in pseudoexfoliation syndrome.
AB  - The phenomenon of protein aggregation is of considerable interest to various
      disciplines, including the field of medicine. A range of disease pathologies are
      associated with this phenomenon. One of the ocular diseases hallmarked by protein
      aggregation is the Pseudoexfoliation (PEX) Syndrome. This condition is
      characterized by the deposition of insoluble proteinaceous material on the
      anterior human lens capsule. Genomic and proteomic analyses have revealed an
      association of specific genetic markers and various proteins, respectively, with
      PEX syndrome. However, the ultrastructure of the protein aggregates is poorly
      characterized. This study seeks to build capacity to determine the molecular
      nature of PEX aggregates on human lens capsules in their native state by AFM
      based antibody recognition imaging. Lysyl oxidase-Like 1 (LOXL1), a protein
      identified as a component of PEX aggregates, is detected by an antibody-modified
      AFM probe. Topographical AFM images and antibody recognition images are obtained
      using three AFM-based techniques: TREC, phase and force-volume imaging. LOXL1 is
      found to be present on the lens capsule surface, and is localized around fibrous
      protein aggregates. Our evaluation shows that TREC imaging is best suited for
      human tissue imaging and holds significant potential for imaging of human disease
      tissues in their native state.

PMID- 21740869
TI  - Gallium-enhanced phase contrast in atom probe tomography of nanocrystalline and
      amorphous Al-Mn alloys.
AB  - Over a narrow range of composition, electrodeposited Al-Mn alloys transition from
      a nanocrystalline structure to an amorphous one, passing through an intermediate
      dual-phase nanocrystal/amorphous structure. Although the structural change is
      significant, the chemical difference between the phases is subtle. In this study,
      the solute distribution in these alloys is revealed by developing a method to
      enhance phase contrast in atom probe tomography (APT). Standard APT data analysis
      techniques show that Mn distributes uniformly in single phase (nanocrystalline or
      amorphous) specimens, and despite some slight deviations from randomness,
      standard methods reveal no convincing evidence of Mn segregation in dual-phase
      samples either. However, implanted Ga ions deposited during sample preparation by
      focused ion-beam milling are found to act as chemical markers that preferentially
      occupy the amorphous phase. This additional information permits more robust
      identification of the phases and measurement of their compositions. As a result,
      a weak partitioning tendency of Mn into the amorphous phase (about 2 at%) is
      discerned in these alloys.

PMID- 21740870
TI  - Three dimensional atom probe imaging of GaAsSb quantum rings.
AB  - Unambiguous evidence of ring-shaped self-assembled GaSb nanostructures grown by
      molecular beam epitaxy is presented on the basis of atom-probe tomography
      reconstructions and dark field transmission electron microscopy imaging. The GaAs
      capping process causes a strong segregation of Sb out of the center of GaSb
      quantum dots, leading to the self-assembled GaAs(x)Sb(1-x) quantum rings of 20-30
      nm in diameter with x ~ 0.33.

PMID- 21740871
TI  - MEGACELL: a nanocrystal model construction software for HRTEM multislice
      simulation.
AB  - Image simulation has an invaluable importance for the accurate analysis of High
      Resolution Transmission Electron Microscope (HRTEM) results, especially due to
      its non-linear image formation mechanism. Because the as-obtained images cannot
      be interpreted in a straightforward fashion, the retrieval of both qualitative
      and quantitative information from HRTEM micrographs requires an iterative process
      including the simulation of a nanocrystal model and its comparison with
      experimental images. However most of the available image simulation software
      requires atom-by-atom coordinates as input for the calculations, which can be
      prohibitive for large finite crystals and/or low-symmetry systems and zone axis
      orientations. This paper presents an open source citation-ware tool named
      MEGACELL, which was developed to assist on the construction of nanocrystals
      models. It allows the user to build nanocrystals with virtually any convex
      polyhedral geometry and to retrieve its atomic positions either as a plain text
      file or as an output compatible with EMS (Electron Microscopy Software) input
      protocol. In addition to the description of this tool features, some construction
      examples and its application for scientific studies are presented. These studies
      show MEGACELL as a handy tool, which allows an easier construction of complex
      nanocrystal models and improves the quantitative information extraction from
      HRTEM images.

PMID- 21740872
TI  - Local estimation of lattice constants in HRTEM images.
AB  - A model-based approach to estimate lattice constants from an atomically resolved
      HRTEM image is presented. The approach only utilizes the inherent periodicity of
      these images and does not require a centrosymmetric structure of the specimen.
      This allows the evaluation of, for instance, wurtzite-based materials like
      InGaN/GaN heterostructures. The lattice constants are determined within
      precisions below 3 pm from areas only a few unit cells large. This makes this
      method suitable for further strain/compositional analysis. Furthermore, the
      impact of the approximations of the true detector's covariance matrices on the
      assessment of the model-based approach is investigated, and insights into the
      quality of these noise models of the detector are gained.

PMID- 21740873
TI  - A high signal-to-noise ratio toroidal electron spectrometer for the SEM.
AB  - This paper presents a high signal-to-noise ratio electron energy spectrometer
      attachment for the scanning electron microscope (SEM), designed to measure
      changes in specimen surface potential from secondary electrons and extract
      specimen atomic number information from backscattered electrons. Experimental
      results are presented, which demonstrate that the spectrometer can in principle
      detect specimen voltage changes well into the sub-mV range, and distinguish close
      atomic numbers by a signal-to-noise ratio of better than 20. The spectrometer has
      applications for quantitatively mapping specimen surface voltage and atomic
      number variations on the nano-scale.

PMID- 21740874
TI  - Spatially resolved diffractometry with atomic-column resolution.
AB  - We demonstrate spatially resolved diffractometry in which diffraction patterns
      are acquired at two-dimensional positions on a specimen using scanning
      transmission electron microscopy (STEM), resulting in four-dimensional data
      acquisition. A high spatial resolution of about 0.1 nm is achieved using a
      stabilized STEM instrument, a spherical aberration corrector and various post
      acquisition data processings. We have found a few novel results in the radial and
      the azimuthal scattering angle dependences of atomic-column contrast in STEM
      images. Atomic columns are clearly observed in dark field images obtained using
      the excess Kikuchi band intensity even in small solid-angle detection. We also
      find that atomic-column contrasts in dark field images are shifted in the order
      of a few tens of picometers on changing the azimuthal scattering angle. This
      experimental result is approximately interpretable on the basis of the impact
      parameter in Rutherford scattering. Spatially resolved diffractometry provides
      fundamental knowledge related to various STEM techniques, such as annular dark
      field (ADF) and annular bright field (ABF) imaging, and it is expected to become
      an analytical platform for advanced STEM imaging.

PMID- 21740875
TI  - Direct deformation study of AFM probe tips modified by hydrophobic alkylsilane
      self-assembled monolayers.
AB  - The in-use wear of atomic force microscopy (AFM) probe tips is crucial for the
      reliability of AFM measurements. Increase of tip size for several nanometers is
      difficult to monitor but it can already taint subsequent AFM data. We have
      developed a method to study the shape evolution of AFM probe tips in nanometer
      scale. This approach provides direct comparison of probe shape profiles, and thus
      can help in evaluation of the level of tip damage and quality of acquired AFM
      data. Consequently, the shape degradation of probes modified by hydrophobic
      alkylsilane self-assembled monolayers (SAMs) was studied. The tip wear length and
      wear volume were adopted to quantitatively verify the effectiveness of
      hydrophobic coatings. When compared with their silicon counterparts, probes
      modified by SAM materials exhibit superior wear-resistant behavior in tapping
      mode scans.

PMID- 21740876
TI  - Digital in-line X-ray holography with zone plates.
AB  - Single pulse imaging with radiation provided by free-electron laser sources is a
      promising approach towards X-ray microscopy, which is expected to provide high
      resolution images of biological samples unaffected by radiation damage. One fully
      coherent imaging technique for this purpose is digital in-line holography. Key to
      its successful application is the creation of X-ray point sources with high
      photon flux. In this study we applied zone plates to create such point sources
      with synchrotron radiation provided by the storage ring BESSY II. The obtained,
      divergent light cone is applied to holographic microscopy of biological objects
      such as critical point dried Navicula perminuta diatoms and human cells using
      photons with an energy of 250 eV. Compared to conventional experiments employing
      pinholes, exposure times are reduced by two orders of magnitude.

PMID- 21740877
TI  - A genetic contribution to risk for postoperative junctional ectopic tachycardia
      in children undergoing surgery for congenital heart disease.
AB  - BACKGROUND: Junctional ectopic tachycardia (JET) is a common arrhythmia
      complicating pediatric cardiac surgery, with many identifiable clinical risk
      factors but no genetic risk factors to date. OBJECTIVE: To test the hypothesis
      that the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism
      associates with postoperative JET. METHODS: DNA samples were collected from
      children undergoing the Norwood procedure; arterial switch operation; and repairs
      of Tetralogy of Fallot, balanced atrioventricular septal defect, and ventricular
      septal defect at a single center. The incidence of postoperative JET was
      associated with previously identified clinical risk factors and ACE I/D genotype.
      RESULTS: Of the 174 children who underwent the above-mentioned surgeries, 21%
      developed JET. Postoperative JET developed in 31% of children with the D/D
      genotype but only in 16% of those with the I/I genotype or the I/D genotype (P =
      .02). Clinical predictors of JET were selected a priori and included age,
      inotrope score, cardiopulmonary bypass time, and cross-clamp time. Multivariable
      logistic regression identified a significant correlation between the D/D genotype
      and postoperative JET independent of these predictors (odds ratio = 2.4; 95%
      confidence interval, 1.04-5.34; P = .04). A gene-dose effect was apparent in the
      homogeneous subset of subjects with atrioventricular septal defect (58% JET in
      D/D subjects, 12% JET in I/D subjects, and 0% JET in I/I subjects; P <.01).
      CONCLUSION: The common ACE deletion polymorphism is associated with a greater
      than 2-fold increase in the odds of developing JET in children undergoing
      surgical repair of atrioventricular septal defect, Tetralogy of Fallot,
      ventricular septal defect or the Norwood and arterial switch procedures. These
      findings may support the potential role of the renin-angiotensin-aldosterone
      system in the etiology of JET.

PMID- 21740878
TI  - Prolonged QRS duration and sudden cardiac death risk stratification: not yet
      ready for prime time.

PMID- 21740879
TI  - Influence of body mass index on quality of life in atrial fibrillation patients
      undergoing catheter ablation.
AB  - BACKGROUND: Obesity increases the risk of atrial fibrillation (AF), and AF
      seriously impairs the quality of life (QoL). However, it is not known whether
      body mass index (BMI) has any direct influence on QoL in AF. OBJECTIVE: To study
      the association between baseline BMI and QoL improvement in patients with AF
      following catheter ablation. METHODS: Six hundred sixty patients with AF (62 +/-
      10 years, male 69%, paroxysmal AF 27%, persistent AF 31%, long-standing
      persistent AF 42%) made up the study population. On the basis of the baseline
      BMI, patients were categorized into 2 groups: normal (BMI < 25) and
      overweight/obese (BMI >= 25). The QoL survey was done at baseline and at 12-month
      postablation by using the Medical Outcomes Study Short Form-36 (SF-36), Beck
      Depression Inventory (BDI), Hospital Anxiety and Depression (HAD) scale, and
      State-Trait Anxiety Inventory (STAI). RESULTS: At baseline, dyslipidemia,
      hypertension, diabetes, coronary artery disease, and large left atrium had higher
      prevalence in the overweight/obese population. In addition, the preprocedure QoL
      scores on the SF-36, HAD scale, and STAI were significantly lower in this group
      than in the normal-BMI group. At the 12-month postablation assessment, no
      significant improvement in QoL score was noted in the normal-BMI group. However,
      in the overweight/obese group, QoL scores improved significantly in all scales,
      except the physical functioning and bodily pain categories of SF-36. Long-term
      ablation success was not different across the groups (69% normal BMI, 63% high
      BMI, log-rank P = .109). Patients with successful ablation showed significant
      improvement in QoL scores compared with those who failed. The multivariable
      analysis revealed the baseline QoL score and BMI >= 25 to be independent
      predictors of QoL improvement. CONCLUSION: Obese patients with AF tend to have a
      better postablation QoL outcome than do their nonobese counterparts.

PMID- 21740880
TI  - Ischemic ventricular arrhythmias: experimental models and their clinical
      relevance.
AB  - In the United States, sudden cardiac death accounts for an estimated 300,000 to
      350,000 cases each year, with 80,000 presenting as the first manifestation of a
      preexisting, sometimes unrecognized, coronary artery disease. Acute myocardial
      infarction (AMI)-induced ventricular fibrillation frequently occurs without
      warning, often leading to death within minutes in patients who do not receive
      prompt medical attention. Identification of patients at risk for AMI-induced
      lethal ventricular arrhythmias remains an unmet medical need. Recent studies
      suggest that a genetic predisposition may significantly contribute to the
      vulnerability of the ischemic myocardium to ventricular tachycardia/ventricular
      fibrillation. Numerous experimental models have been developed for the purpose of
      advancing our understanding of the mechanisms responsible for the development of
      cardiac arrhythmias in the setting of ischemia and with the aim of identifying
      antiarrhythmic therapies that could be of clinical benefit. While our
      understanding of the mechanisms underlying AMI-induced ventricular arrhythmias is
      coming into better focus, the risk stratification of patients with AMI remains a
      major challenge. This review briefly discusses our current state of knowledge
      regarding the mechanisms of ischemic ventricular arrhythmias and their temporal
      distribution as revealed by available experimental models, how these correlate
      with the clinical syndromes, as well as prospective prophylactic therapies for
      the prevention and treatment of ischemia-induced life-threatening arrhythmias.

PMID- 21740881
TI  - Coronary artery pathophysiology after radiofrequency catheter ablation: review
      and perspectives.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has proven to be an effective and safe
      treatment in patients with ventricular and atrial tachyarrhythmias. Among
      complications arising after RFA, the incidence of coronary artery (CA) injury is
      exceedingly low. When CA injury does occur, however, it can be clinically
      devastating. The proximity of CAs to common ablation sites suggests that the
      relationship between RFA and CA perfusion pathophysiology is important for
      optimal lesion formation and safe arrhythmia treatments. OBJECTIVE: Although
      others have described the presentation and outcomes of patients with CA injury
      after ablation, a review that consolidates the mechanisms of CA injury after RFA
      has yet to be presented in the cardiology literature. METHODS: We conducted an
      extensive literature search of studies published over the past 30 years that
      relate the biophysics of RFA with CA perfusion pathophysiology and injury.
      RESULTS: We present a review of the dynamic relationship between RFA and CA
      perfusion. We describe RFA lesion pathology, mechanisms of CA injury from RFA,
      and factors that influence lesion formation, such as convective cooling and the
      shadow effect. CONCLUSION: We summarize methods to mitigate CA injury after RFA
      and propose new research avenues to optimize lesion formation and safe arrhythmia
      treatments when tissue is ablated in the vicinity of CAs.

PMID- 21740882
TI  - Autoantibodies and cardiac arrhythmias.
AB  - Autoimmune diseases are associated with significant morbidity and mortality,
      afflicting about 5% of the US population. They encompass a wide range of
      disorders that affect all organs of the human body and have a predilection for
      women. In the past, autoimmune pathogenesis was not thought to be a major
      mechanism for cardiovascular disorders, and potential relationships remain
      understudied. However, accumulating evidence suggests that a number of vascular
      and cardiac conditions are autoimmune mediated. Recent studies indicate that
      autoantibodies play an important role in the development of cardiac arrhythmias,
      including atrial fibrillation, modulation of autonomic influences on heart rate
      and rhythm, conduction system abnormalities, and ventricular arrhythmias. This
      article will review the current evidence for the role of autoantibodies in the
      development of cardiac arrhythmias.

PMID- 21740883
TI  - A straightforward, reliable technique for retaining vascular access during lead
      replacement.

PMID- 21740884
TI  - Lesion recovery, epicardial substrate, or new circuit? Exploring the dark side of
      recurrent ventricular tachycardia after endocardial ablation.

PMID- 21740885
TI  - Tinker, tailor: foretelling the future in long QT syndrome.

PMID- 21740886
TI  - Gene therapy for AF: A dream too far?

PMID- 21740887
TI  - Causes of nonischemic sudden cardiac death in the current era.
AB  - BACKGROUND: Previous data have shown that various nonischemic cardiac diseases
      account for about 20% of sudden cardiac deaths (SCDs) and that dilated and
      hypertrophic cardiomyopathy (CM) are major causes of nonischemic SCD. OBJECTIVE:
      The purpose of this study was to define the prevalence and causes of SCD due to
      nonischemic CM in the current era given the substantial change in the diagnosis
      and treatment of cardiac diseases and in lifestyle patterns. METHODS: A total of
      2661 consecutive victims of SCD from among a population of approximately 470,000
      inhabitants in the Province of Oulu, Northern Finland, were included in the
      study. The causes of deaths were determined from the uniformly required autopsies
      of SCD victims in Finland, plus available medical records and standardized
      questionnaires. RESULTS: Nonischemic cause of SCD was found in 579 victims (21.8%
      of all the SCDs). Mean age (+/- SD) was 55 (+/-12) years; 78% were males. After
      subgrouping the nonischemic SCDs into various categories, SCDs associated most
      closely with obesity (23.7%), followed by alcoholic CM (19.0%), hypertensive CM
      (15.5%), and fibrotic CM (13.6%). Fibrotic CM was the most common association
      with SCD in subjects younger than 40 years (28.3%), whereas alcoholic CM was the
      most common cause of death in subjects between 40 and 59 years of age (25.8%).
      CONCLUSION: CM related to obesity, fibrotic CM, and alcoholic CM are commonly
      associated with nonischemic SCD in the current era. The association of SCD with
      fibrotic CM is notably frequent among victims younger than 40 years.

PMID- 21740888
TI  - Antitumor necrosis factor-alpha antibody-coupled gold nanorods as nanoprobes for
      molecular optoacoustic imaging in arthritis.
AB  - Optoacoustic molecular imaging can provide spatially resolved information about
      the presence of molecular markers in vivo. We synthesized elongated gold nanorods
      having an absorption maximum in the range of 1064 nm modified with the antibodies
      infliximab and certolizumab for targeting TNF-alpha to detect inflammation in
      arthritic mouse knees. We showed an differential enhancement of optoacoustic
      signal amplitudes after the injection of infliximab-, but not certolizumab
      modified and PEGylated control particles on arthritic and healthy control mice by
      using a fast-scanning optoacoustic imaging platform based on a pulsed Nd:YAG
      laser and a single focused ultrasound transducer. The excellent photoacoustic
      properties of the gold nanorods confirmed the overexpression of TNF-alpha in
      arthritic knees. Due to the uncomplicated coupling chemistry and the scalability
      of ultrasound-based imaging approaches, these results potentially allow a
      transfer to various preclinical and clinical applications. From the Clinical
      Editor: Gold nanorods were modified with TNF-alpha targeting antibodies and used
      to detect inflammation in arthritic mouse knees via optoaoustic imaging. A fast
      scanning optoacoustic imaging platform based on a pulsed Nd:YAG laser and a
      single focused ultrasound transducer was utilized for imaging. The excellent
      photoacoustic properties of these gold nanorods confirmed the overexpression of
      TNF-alpha, paving the way towards further preclinical and future clinical
      applications.

PMID- 21740889
TI  - Induction of neurite-outgrowth in PC12 cells by alpha-toxin from Clostridium
      perfringens.
AB  - Alpha-toxin-induced phosphorylation of PDK1 via the tyrosine kinase A (TrkA)
      receptor signaling pathway plays an important role in the activation of rabbit
      neutrophils. The relation between the toxin and TrkA, however, remains poorly
      understood. Here, we show that the toxin-induced phosphorylation of TrkA is
      closely related to the induction of neurite-outgrowth in PC12 cells. The toxin
      induced neurite-outgrowth and phosphorylation of TrkA in the cells in a dose
      dependent manner. K252a, a TrkA inhibitor, and shRNA for TrkA inhibited the toxin
      induced neurite-outgrowth, and phosphorylation of TrkA and ERK1/2. PD98059, an
      inhibitor of the ERK1/2 cascade, inhibited phosphorylation of ERK1/2 and the
      neurite-outgrowth induced by alpha-toxin. The wild-type toxin induced the
      formation of diacylglycerol, and neurite-outgrowth, but H148G, a variant toxin
      which binds to cell membranes and has lost the enzymatic activity did not. We
      demonstrated that the phosphorylation of TrkA through the phospholipid metabolism
      induced by the toxin synergistically play a key role in neurite-outgrowth.

PMID- 21740890
TI  - Iron(III) mesoporphyrin IX and iron(III) deuteroporphyrin IX bind to the
      Porphyromonas gingivalis HmuY hemophore.
AB  - Porphyromonas gingivalis acquires heme through an outer-membrane heme transporter
      HmuR and heme-binding hemophore-like lipoprotein HmuY. Here, we compare binding
      of iron(III) mesoporphyrin IX (mesoheme) and iron(III) deuteroporphyrin IX
      (deuteroheme) to HmuY with that of iron(III) protoporphyrin IX (protoheme) and
      protoporphyrin IX (PPIX) using spectroscopic methods. In contrast to PPIX,
      mesoheme and deuteroheme enter the HmuY heme cavity and are coordinated by His134
      and His166 residues in a fully analogous way to protoheme binding. However, in
      the case of deuteroheme two forms of HmuY-iron porphyrin complex were observed
      differing by a 180 degrees  rotation of porphyrin about the alpha-gamma-meso
      carbon axis. Since the use of porphyrins either as active photosensitizers or in
      combination with antibiotics may have therapeutic value for controlling bacterial
      growth in vivo, it is important to compare the binding of heme derivatives to
      HmuY.

PMID- 21740891
TI  - Interaction of plasma membrane Ca(2+)-ATPase isoform 4 with calcineurin A:
      implications for catecholamine secretion by PC12 cells.
AB  - PMCA1-4 isoforms have been recently recognised as regulators of various
      signalling pathways in mammalian cells. PMCAs were found to interact with
      calcineurin A in an isoform specific manner. In this study we focus on the
      interaction of calcineurin A with PMCA4 and its effect on catecholamine secretion
      in PC12 cells with reduced PMCA2 or PMCA3 content. Reduction of synthesis of
      PMCA2 or PMCA3 led to upregulation of PMCA4 manifested by preferential
      interaction of PMCA4 with calcineurin A. On the other hand, we observed a
      significant reduction of dopamine secretion, which did not correspond with an
      increased [Ca(2+)](c). This result indicates that the interaction of PMCA4 with
      calcineurin A plays a regulatory role in the signalling during catecholamine
      secretion.

PMID- 21740892
TI  - Possibility of increasing cholesterol efflux by adiponectin and its receptors
      through the ATP binding cassette transporter A1 in HEK293T cells.
AB  - A decrease in adiponectin secretion leads to the early stage of atherosclerosis.
      Discoidal high-density lipoproteins (HDL) accept the cholesterol that effluxes
      from cells expressing the ATP binding cassette transporter A1 (ABCA1) in the
      first step of reverse cholesterol transport (RCT). Recently, a new therapeutic
      strategy involving reconstituted (r)HDL has been shown to enhance RCT. Therefore,
      we hypothesized that adiponectin may increase the efflux associated with ABCA1
      and also enhance rHDL-induced efflux in human embryonic kidney 293 (HEK293T)
      cells. We transfected adiponectin receptor 1 and 2 (AdipoR1 and AdipoR2) cDNA
      into cells. The transfected cells were labeled with [(3)H]cholesterol following
      cholesterol loading with or without adiponectin for 24h. The levels of
      cholesterol efflux were analyzed using a liquid scintillation counter. Treatment
      with adiponectin was associated with significantly higher levels of efflux in
      AdipoR1- and AdipoR2-transfected cells. Interestingly, rHDL-induced cholesterol
      efflux was enhanced in the presence of adiponectin. The down-regulation of
      adiponectin receptors using short-hairpin RNA decreased rHDL-induced cholesterol
      efflux with the down-regulation of ABCA1. In summary, adiponectin and its
      receptors increased cholesterol efflux and also enhanced rHDL-induced efflux at
      least partially through an ABCA1 pathway. These results suggest that adiponectin
      may enhance the RCT system and induce an anti-atherogenic effect.

PMID- 21740893
TI  - Hyal2 is a glycosylphosphatidylinositol-anchored, lipid raft-associated
      hyaluronidase.
AB  - The rapid turnover rate of hyaluronan (HA), the major unbranched
      glycosaminoglycan of the extracellular matrix, is dependent on hyaluronidases.
      One of them, hyaluronidase-2 (Hyal2), degrades HA into smaller fragments endowed
      with specific biological activities such as inflammation and angiogenesis. Yet
      the cellular environment of Hyal2, a purported glycosylphosphatidylinositol (GPI)
      anchored protein, remains uncertain. We have examined the membrane association of
      Hyal2 in MDA-MB231 cancer cells where it is highly expressed and in COS-7 cells
      transfected with native or fluorescent Hyal2 constructs. In both cell types,
      Hyal2 was strongly associated with cell membrane fractions from which it could be
      extracted using a Triton X-114 treatment (hydrophobic phase) but not an osmotic
      shock or an alkaline carbonate solution. Treatment of membrane preparations with
      phosphatidylinositol-specific phospholipase C released immunoreactive Hyal2 into
      the aqueous phase, confirming the protein is attached to the membrane through a
      functional GPI anchor. Hyal2 transfected in COS-7 cells was associated with
      detergent-resistant, cholesterol-rich membranes known as lipid rafts. The
      cellular immunofluorescent pattern of Hyal2 was conditioned by the presence of a
      GPI anchor. In summary, the strong membrane association of Hyal2 through its GPI
      anchor demonstrated in this study using biochemical methods suggests that the
      main activity of this enzyme is located at the level of the plasma membrane in
      close contact with the pericellular HA-rich glycocalyx, the extracellular matrix,
      or possibly endocytic vesicles.

PMID- 21740895
TI  - Effect of sample dilution on serum free light chain concentration by
      immunonephelometric assay.
AB  - BACKGROUND: Free light chains (FLC) are useful biomarkers in the assessment of
      plasma cell disorders. Concerns have been raised about some technical aspects of
      the assay. This report examined the occurrence of dilution anomalies and/or
      antigen excess. METHODS: FLC were determined on a BNII instrument at at-least two
      dilutions (100- and 2000-fold) in 2088 consecutive samples from 865 different
      patients. In part of them, the 400-fold dilution was also available. RESULTS:
      Higher than 2-fold differences and inconsistencies ["<" or ">" result at one
      dilution not consistent with the result obtained at another dilution] between the
      100- and 2000-fold dilutions were found in 12.7% of patients for kappa FLC and in
      3.1% of patients for lambda FLC. More than 4-fold differences between results
      obtained at the 2000-fold and the 100-fold dilutions were observed in 5.4% of
      patients for kappa FLC and in 1.2% of patients for lambda FLC. CONCLUSIONS: The
      FLC assay on BNII suffers from sample dilution anomalies and/or failure of
      antigen excess detection in a substantial fraction of patients. Laboratory
      professionals and clinicians should be alert to such analytical difficulties.

PMID- 21740896
TI  - Association of STAT4 polymorphisms with susceptibility to primary membranous
      glomerulonephritis and renal failure.
AB  - BACKGROUND: Membranous glomerulonephritis (MGN) is one of common causes of
      idiopathic nephrotic syndrome in adults, and 25% of MGN patients proceed to end
      stage renal disease. STAT4 gene polymorphisms have been reported to be associated
      with many inflammatory diseases. The objective of this study was to clarify the
      relationship between STAT4 gene polymorphisms and the pathogenesis of MGN.
      METHODS: We investigated the association of three STAT4 gene polymorphisms
      (rs3024912, rs3024908, and rs3024877) with the susceptibility to MGN in 403
      Taiwanese populations (138 MGN patients and 265 controls). RESULTS: The results
      indicated that the statistically significant difference in genotype frequency
      distribution was found at rs3024908 SNP in MGN patients and control groups
      (p=0.014). In addition, the individuals with the GG genotype at rs3024912 SNP may
      have a higher risk in kidney failure of MGN patients (adjusted odds ratio
      [OR]=3.255; 95% confidence interval [CI]=1.155-9.176, p=0.026). CONCLUSIONS: Our
      data provide a new information that the STAT4 (rs3024912 and rs3024908)
      polymorphisms may be the underlying cause of MGN, and these polymorphisms
      revealed by this study warrant further investigation.

PMID- 21740897
TI  - Analysis of urinary nucleosides as potential tumor markers in human breast cancer
      by high performance liquid chromatography/electrospray ionization tandem mass
      spectrometry.
AB  - BACKGROUND: Breast cancer is the most common female cancer and the fourth leading
      cause of cancer death among women in Taiwan. We measured urinary nucleoside
      levels in female breast cancer patients (n=36) to evaluate the diagnostic value
      of nucleosides as potential tumor markers. METHODS: Purification of urinary
      nucleosides was performed using a 96-well solid phase extraction (SPE, cation
      exchange column) procedure to decrease the variation between the single column
      preparations and to shorten the pretreatment time. Cation-exchange allows for the
      comprehensive purification of modified nucleosides, such as 2-deoxynucleosides,
      that are not purifiable by phenylboronic acid-based SPE. High-performance liquid
      chromatography (HPLC) coupled with mass spectrometry (MS) in selected reaction
      monitoring (SRM) mode was used to quantify multiple nucleosides. Tubercidin was
      used as an internal standard. The qualitative parameters, retention time, and the
      parent and daughter ions used revealed that the method was more specific and
      sensitive than traditional UV detection. RESULTS: Urinary levels of 3
      nucleosides, cytidine, 3-methylcytidine, and inosine were significantly higher in
      breast cancer patients than in normal controls (p<0.01). The discriminative
      powers of cytidine, 3-methylcytidine, and inosine were 58%, 58%, and 62%,
      respectively. CONCLUSIONS: LC/MS/MS is a highly specific and sensitive method for
      rapidly screening a large number of urinary nucleosides that may be potential
      cancer markers. The 3-methylcytidine may be a candidate marker for breast cancer.

PMID- 21740894
TI  - Recent advances in understanding nicotinic receptor signaling mechanisms that
      regulate drug self-administration behavior.
AB  - Tobacco smoking is one of the leading causes of disease and premature death in
      the United States. Nicotine is considered the major reinforcing component in
      tobacco smoke responsible for tobacco addiction. Nicotine acts in the brain
      through the neuronal nicotinic acetylcholine receptors (nAChRs). The predominant
      nAChR subtypes in mammalian brain are those containing alpha4 and beta2 subunits.
      The alpha4beta2 nAChRs, particularly those located in the mesoaccumbens dopamine
      pathway, play a key role in regulating the reinforcing properties of nicotine.
      Considering that twelve mammalian nAChR subunits have been cloned, it is likely
      that nAChRs containing subunits in addition to, or other than, alpha4 and beta2
      also play a role in the tobacco smoking habit. Consistent with this possibility,
      human genome-wide association studies have shown that genetic variation in the
      CHRNA5-CHRNA3-CHRNB4 gene cluster located in chromosome region 15q25, which
      encode the alpha5, alpha3 and beta4 nAChR subunits, respectively, increases
      vulnerability to tobacco addiction and smoking-related diseases. Most recently,
      alpha5-containing nAChRs located in the habenulo-interpeduncular tract were shown
      to limit intravenous nicotine self-administration behavior in rats and mice,
      suggesting that deficits in alpha5-containing nAChR signaling in the habenulo
      interpeduncular tract increases vulnerability to the motivational properties of
      nicotine. Finally, evidence suggests that nAChRs may also play a prominent role
      in controlling consumption of addictive drugs other than nicotine, including
      cocaine, alcohol, opiates and cannabinoids. The aim of the present review is to
      discuss recent preclinical findings concerning the identity of the nAChR subtypes
      that regulate self-administration of nicotine and other drugs of abuse.

PMID- 21740898
TI  - Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated
      protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.
AB  - Cilia are ubiquitous cell surface projections that mediate various sensory- and
      motility-based processes and are implicated in a growing number of multi-organ
      genetic disorders termed ciliopathies. To identify new components required for
      cilium biogenesis and function, we sought to further define and validate the
      transcriptional targets of DAF-19, the ciliogenic C. elegans RFX transcription
      factor. Transcriptional profiling of daf-19 mutants (which do not form cilia) and
      wild-type animals was performed using embryos staged to when the cell types
      developing cilia in the worm, the ciliated sensory neurons (CSNs), still
      differentiate. Comparisons between the two populations revealed 881
      differentially regulated genes with greater than a 1.5-fold increase or decrease
      in expression. A subset of these was confirmed by quantitative RT-PCR. Transgenic
      worms expressing transcriptional GFP fusions revealed CSN-specific expression
      patterns for 11 of 14 candidate genes. We show that two uncharacterized candidate
      genes, termed dyf-17 and dyf-18 because their corresponding mutants display dye
      filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the
      base of cilia and is specifically required for building the distal segment of
      sensory cilia. DYF-18 is an evolutionarily conserved CDK7/CCRK/LF2p-related
      serine/threonine kinase that is necessary for the proper function of
      intraflagellar transport, a process critical for cilium biogenesis. Together, our
      microarray study identifies targets of the evolutionarily conserved RFX
      transcription factor, DAF-19, providing a rich dataset from which to uncover-in
      addition to DYF-17 and DYF-18-cellular components important for cilium formation
      and function.

PMID- 21740899
TI  - Boule-like genes regulate male and female gametogenesis in the flatworm
      Macrostomum lignano.
AB  - Members of the DAZ (Deleted in AZoospermia) gene family are important players in
      the process of gametogenesis and their dysregulation accounts for 10% of human
      male infertility. Boule, the ancestor of the family, is mainly involved in male
      meiosis in most organisms. With the exception of Drosophila and C. elegans,
      nothing is known on the function of boule in non-vertebrate animals. In the
      present study, we report on three boule orthologues in the flatworm Macrostomum
      lignano. We demonstrate that macbol1 and macbol2 are expressed in testes whilst
      macbol3 is expressed in ovaries and developing eggs. Macbol1 RNAi blocked
      spermatocyte differentiation whereas macbol2 showed no effect upon RNAi
      treatment. Macbol3 RNAi resulted in aberrant egg maturation and led to female
      sterility. We further demonstrated the evolutionary functional conservation of
      macbol1 by introducing this gene into Drosophila bol(1) mutants. Macbol1 was able
      to rescue the progression of fly meiotic divisions. In summary, our findings
      provide evidence for an involvement of boule genes in male and female gamete
      development in one organism. Furthermore, boule gene function is shown here for
      the first time in a lophotrochozoan. Our results point to a more diverse
      functional assignment of boule genes. Therefore, a better understanding of boule
      function in flatworms can help to elucidate the molecular mechanisms of and
      concomitant infertility in higher organisms including humans.

PMID- 21740900
TI  - Tenascin-C in the extracellular matrix promotes the selection of highly
      proliferative and tubulogenesis-defective endothelial cells.
AB  - The extracellular matrix (ECM) contains important cues for tissue homeostasis and
      morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in
      remodeling tissues and cancer. In the present work, we studied the effect of
      different ECM-which exhibited a significant diversity in their TN-C content-in
      endothelial survival, proliferation and tubulogenic differentiation: autologous
      (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast
      ECM, bearing both high TN-C and FN contents; and finally, glioma-derived
      matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to
      the immobilized matrix produced by U373 MG glioma cells, but significantly
      detached and died by anoikis (50 to 80%) after 24h, as compared with cells
      incubated with endothelial and fibroblast matrices. Surviving endothelial cells
      (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube
      like structures in vitro than cells grown on non-tumoral matrices. An antibody
      against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from
      the tubulogenic defect, indicating that this molecule is responsible for the
      selection of highly proliferative and tubulogenic defective endothelial cells.
      Interestingly, by using defined substrata, in conditions that mimic glioma and
      normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C
      induced selection of endothelial cells. Our data show that TN-C is able to
      modulate endothelial branching morphogenesis in vitro and, since it is prevalent
      in matrices of injured and tumor tissues, also suggest a role for this protein in
      vascular morphogenesis, in these physiological contexts.

PMID- 21740901
TI  - Anatomical evidence of photoreceptor degeneration induced by iodoacetic acid in
      the porcine eye.
AB  - Iodoacetic acid (IAA) induces photoreceptor (PR) degeneration in small animal
      models, however, eye size and anatomic differences detract from the usefulness of
      these models for studying retinal rescue strategies intended for humans. Porcine
      eyes are closer in size to human eyes and have a rich supply of rod and cones.
      This study investigated whether IAA also produced PR degeneration in the porcine
      retina, whether the damage was preferential for rods or cones, and whether IAA
      induced remodeling of the inner retina. Pigs were given a single i.v. injection
      of IAA and were euthanized 2-5 weeks later. Eyes were enucleated and immersed in
      fixative. Forty-six eyes were studied: Control (n = 13), and from pigs that had
      received the following IAA doses: 5.0 mg/kg (n = 7); 7.5 mg/kg (n = 10); 10.0
      mg/kg (n = 6); 12.0 mg/kg (n = 6). Tissue was retrieved from four retinal
      locations: 8 mm and 2 mm above the dorsal margin of the optic disc, and 2 mm and
      8 mm below the disc, and was processed for conventional histology,
      immunohistochemistry, and transmission electron microscopy. At 5.0 mg/kg IAA
      produced mild, variable cell loss, but remaining cells exhibited normal features.
      At doses above 5.0 mg/kg, a dose-dependent reduction was observed in the length
      of PR inner and outer segments, and in the number of PR nuclei. Specific labeling
      revealed a massive dropout of rod cell bodies with relative sparing of cone cell
      bodies, and electron microscopy revealed a reduction in the number of PR synaptic
      terminals. Mild dendritic retraction of rod bipolar cells and hypertrophy of
      Muller cell stalks was also observed, although the inner nuclear layer appeared
      intact. The porcine IAA model may be useful for developing and testing retinal
      rescue strategies for human diseases in which rods are more susceptible than
      cones, or are affected earlier in the disease process.

PMID- 21740902
TI  - Effect of different concentrations of serotonin, histamine and insulin on the
      hormone (serotonin and ACTH) production of Tetrahymena in nutrient-free
      physiological milieu.
AB  - Cell populations of Tetrahymena pyriformisGL were kept in nutrient-free (Losina)
      milieu and treated with different (10(-6)-10(-21)M) concentrations of serotonin,
      histamine or insulin for 30 min. Following that the hormone (serotonin and
      adrenocorticotropin (ACTH) content of the cells were measured by
      immunocytochemical flow cytometric method. Serotonin reduced histamine when
      applied in 10(-12) and 10(-15)M concentrations, while elevated ACTH levels when
      applied in 10(-6), 10(-9) and 10(-21)M concentrations. Histamine reduced
      serotonin concentration at 10(-9)-10(-21)M concentrations and increased ACTH in
      10(-6)M. Insulin elevated both hormones' content in each concentration except at
      10(-12)M. The results demonstrate that (1) in nutrient-free conditions the
      hormonal effects differ from that of nutrient-rich (tryptone+yeast) condition;
      (2) there is an optimal hormone concentration, which causes the strongest effect
      and this is different for each hormones; (3) the hormone receptors of Tetrahymena
      are very sensitive; as they react to zeptomolar concentrations. Such small
      concentration is even more effective than higher ones. Since hormones must become
      highly diluted in the natural environment of Tetrahymena, it seems that such low
      concentrations are the actual physiological concentrations.

PMID- 21740903
TI  - Selection and identification of a new adhesion protein of Cryptosporidium parvum
      from a cDNA library by ribosome display.
AB  - In this study, we described a novel display method to identify surface adhesion
      proteins of Cryptosporidium parvum. A cDNA library of the sporozoite and oocyst
      stages of C. parvum was expressed on ribosome and selectively and specifically
      screened with intestinal epithelial cells (IECs) from newborn Cryptosporidium
      free Holstein calves. Proteins were then enriched using a multi-step panning
      procedure. A new surface adherence protein of C. parvum was selected, named Cp20.
      Sequence analyses showed that Cp20 has a N-terminal signal peptide and four
      transmembrane regions. Indirect immunofluorescence assay (IFA) using an antibody
      specific for rCp20 demonstrated that the antibody specifically bound to the
      surface of sporozoites and oocysts. The recombinant plasmid pVAX1-Cp20 was
      constructed to examine the potential of the Cp20 gene as a target for specific
      preventive and therapeutic measures for cryptosporidiosis. The in vivo efficacies
      of the DNA vaccine was tested in BALB/c mice. The results indicated that the DNA
      vaccine elicited significant antibody responses and specific cellular responses
      when compared to control mice that received vector only or PBS. The DNA vaccine
      induced strong protective immune response against C. parvum and lower level of
      the oocysts shedding after challenge infection. This study suggested that Cp20
      could serve as an effective target for specific preventive and therapeutic
      measures for cryptosporidiosis.

PMID- 21740904
TI  - Membrane targeting of palmitoylated Wnt and Hedgehog revealed by chemical probes.
AB  - Palmitoylation of the Wnt and Hedgehog proteins is critical for maintaining their
      physiological functions. To date, there are no reported studies that characterize
      the cellular distribution of the palmitoylated forms of these proteins. Here, we
      describe the subcellular localization of palmitoylated Wnt and Sonic Hedgehog by
      using a highly sensitive and non-radioactive labeling method that utilizes
      alkynyl palmitic acid. We show that palmitoylated Wnt and Sonic Hedgehog localize
      to cellular membrane fractions only, highlighting a role for palmitoylation in
      the membrane association of these proteins. The method described herein has the
      utility to validate inhibitors of Wnt and Hedgehog acyltransferases in drug
      discovery, and enables further investigations of the role of palmitoylation in
      the secretion and signaling of these proteins.

PMID- 21740905
TI  - Cyclin T2: a novel miR-15a target gene involved in early spermatogenesis.
AB  - MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression that
      play important roles in various biological processes. Spermatogenesis is a highly
      regulated process in which diploid spermatogonia eventually differentiate into
      haploid spermatozoa. In this study, we identified four differentially expressed
      miRNAs between two premeiotic male germ cells, made predictions about their
      putative targets, and confirmed cyclin T2 (Ccnt2) as a direct target of miR-15a.
      We also report that miR-15a inhibited muscle differentiation at least in part by
      targeting Ccnt2, which represents a novel interaction. Subsequently, miR-15a and
      Ccnt2 were profiled in developing mice testes to observe their inverse
      correlations in the postnatal 3-week period to understand their roles in
      spermatogenesis.

PMID- 21740906
TI  - Natural polyphenols inhibit different steps of the process of transthyretin (TTR)
      amyloid fibril formation.
AB  - Several natural polyphenols with potent inhibitory effects on amyloid fibril
      formation have been reported. Herein, we studied modulation of transthyretin
      (TTR) fibrillogenesis by selected polyphenols. We demonstrate that both curcumin
      and nordihydroguaiaretic acid (NDGA) bind to TTR and stabilize the TTR tetramer.
      However, while NDGA slightly reduced TTR aggregation, curcumin strongly
      suppressed TTR amyloid fibril formation by generating small "off-pathway"
      oligomers and EGCG maintained most of the protein in a non-aggregated soluble
      form. This indicates alternative mechanisms of action supported by the occurrence
      of different non-toxic intermediates. Moreover, EGCG and curcumin efficiently
      disaggregated pre-formed TTR amyloid fibrils. Our studies, together with the safe
      toxicological profile of these phytochemicals may guide a novel pharmacotherapy
      for TTR-related amyloidosis targeting different steps in fibrillogenesis.

PMID- 21740907
TI  - Mitochondrial DNA protects against salt stress-induced cytochrome c-mediated
      apoptosis in yeast.
AB  - Here we report that budding yeast mitochondrial DNA protects against salt stress
      induced apoptosis. Yeast cells lacking mitochondrial DNA (rho(0)) are
      hypersensitive to salt stress-induced apoptosis, which is mediated by
      mitochondrial cytochrome c release. In addition, cytochrome c expression is
      downregulated upon salt stress, suggesting a transcriptionally regulated,
      homeostatic protection mechanism. The repression of cytochrome c transcription is
      mediated by transcription factor Mig1. Consistently, deletion of MIG1 induces
      cytochrome C transcription and yields rho(0) cells that are more sensitive to
      salt stress. In summary, deletion of mitochondrial function leads to salt stress
      induced transcriptional deregulation of cytochrome C, causing apoptosis in yeast.

PMID- 21740908
TI  - Prepupal diapause and instar IV developmental rates of the spruce beetle,
      Dendroctonus rufipennis (Coleoptera: Curculionidae, Scolytinae).
AB  - The spruce beetle, Dendroctonus rufipennis (Kirby), is an important mortality
      agent of native spruces throughout North America. The life-cycle duration of this
      species varies from 1 to 3 years depending temperature. The univoltine cycle (one
      generation per year) is thought to maximize outbreak risk and accelerate host
      mortality in established outbreaks. Prepupal diapause is associated with the
      semivoltine cycle (one generation per 2 years) and we investigated thermal
      conditions that result in diapause induction. Preliminary experiments used
      respirometry in an attempt to distinguish the diapause state of experimental
      insects but the technique was apparently confounded by low respiration before and
      during pupation, regardless of diapause status. Therefore, diapause induction was
      deduced using developmental delays. The observed developmental response was not a
      "switch", with developmental delay either present or absent, but instead varied
      continuously. We found that temperatures <15 degrees C from instar III through
      mid-instar IV were associated with developmental delays beyond that expected from
      cool temperatures. Moreover, the duration of exposure to cool temperatures was
      important in determining the degree of developmental delay. Small, if any, delays
      were observed if the cumulative exposure to <15 degrees C was <20 d whereas >40 d
      cumulative exposure was associated with distinct developmental suppression.
      Intermediate exposure to cool temperatures resulted in minor developmental
      delays. We used our results to parameterize a maximum likelihood estimation model
      of temperature-dependent instar IV developmental rates, including the effect of
      diapause. This model can be included as part of a spruce beetle phenology model
      for predicting population dynamics.

PMID- 21740909
TI  - Adult human heart slices are a multicellular system suitable for
      electrophysiological and pharmacological studies.
AB  - Electrophysiological and pharmacological data from the human heart are limited
      due to the absence of simple but representative experimental model systems of
      human myocardium. The aim of this study was to establish and characterise adult
      human myocardial slices from small patients' heart biopsies as a simple,
      reproducible and relevant preparation suitable for the study of human cardiac
      tissue at the multicellular level. Vibratome-cut myocardial slices were prepared
      from left ventricular biopsies obtained from end-stage heart failure patients
      undergoing heart transplant or ventricular assist device implantation, and from
      hearts of normal dogs. Multiple slices were prepared from each biopsy. Regular
      contractility was observed at a range of stimulation frequencies (0.1-2 Hz), and
      stable electrical activity, monitored using multi-electrode arrays (MEA), was
      maintained for at least 8 h from slice preparation. ATP/ADP and
      phosphocreatine/creatine ratios were comparable to intact organ values, and
      morphology and gap junction distribution were representative of native
      myocardium. MEA recordings showed that field potential duration (FPD) and
      conduction velocity (CV) in human and dog slices were similar to the values
      previously reported for papillary muscles, ventricular wedges and whole hearts.
      Longitudinal CV was significantly faster than transversal CV, with an anisotropic
      ratio of 3:1 for human and 2.3:1 for dog slices. Importantly, slices responded to
      the application of E-4031, chromanol and 4-aminopyridine, three potassium channel
      blockers known to affect action potential duration, with an increase in FPD. We
      conclude that viable myocardial slices with preserved structural, biochemical and
      electrophysiological properties can be prepared from adult human and canine heart
      biopsies and offer a novel preparation suitable for the study of heart failure
      and drug screening.

PMID- 21740910
TI  - Phenylephrine preconditioning involves modulation of cardiac sarcolemmal K(ATP)
      current by PKC delta, AMPK and p38 MAPK.
AB  - Preconditioning of hearts with the alpha(1)-adrenoceptor agonist phenylephrine
      decreases infarct size and increases the functional recovery of the heart
      following ischaemia-reperfusion. However, the cellular mechanisms responsible for
      this protection are not known. We investigated the role of protein kinase C
      epsilon and delta (PKCepsilon and PKCdelta), AMP-activated protein kinase (AMPK),
      p38 MAPK (p38) and sarcolemmal ATP-sensitive potassium (sarcK(ATP)) channels in
      phenylephrine preconditioning using isolated rat ventricular myocytes.
      Preconditioning of ventricular myocytes with phenylephrine increased the recovery
      of contractile activity following metabolic inhibition and re-energisation from
      30.1+/-1.9% to 66.5+/-5.2% (P<0.01) and increased the peak sarcK(ATP) current
      activated during metabolic inhibition from 32.1+/-1.8 pA/pF to 46.0+/-5.0 pA/pF
      (P<0.05), which was required for protection. Phenylephrine preconditioning
      resulted in a sustained activation of PKCepsilon and PKCdelta, and transient
      activation of AMPK, which was dependent upon activation of PKCdelta but not
      PKCepsilon. P38 was also activated by phenylephrine preconditioning and this was
      blocked by inhibitors of PKCepsilon, PKCdelta or AMPK. Inhibition of PKCdelta,
      AMPK or p38 was sufficient to prevent the increase in current, suggesting that
      these kinases are involved in modulation of sarcK(ATP) channel current by
      phenylephrine preconditioning. However, whilst inhibition of AMPK and p38
      prevented the protection from phenylephrine preconditioning, PKCdelta inhibition
      paradoxically had no effect. The increase in sarcK(ATP) current induced by
      phenylephrine preconditioning requires PKCdelta, AMPK and p38 and may contribute
      to the observed improvement in contractile recovery.

PMID- 21740911
TI  - Caveolae compartmentalise beta2-adrenoceptor signals by curtailing cAMP
      production and maintaining phosphatase activity in the sarcoplasmic reticulum of
      the adult ventricular myocyte.
AB  - Inotropy and lusitropy in the ventricular myocyte can be efficiently induced by
      activation of beta1-, but not beta2-, adrenoceptors (ARs). Compartmentation of
      beta2-AR-derived cAMP-dependent signalling underlies this functional discrepancy.
      Here we investigate the mechanism by which caveolae (specialised sarcolemmal
      invaginations rich in cholesterol and caveolin-3) contribute to compartmentation
      in the adult rat ventricular myocyte. Selective activation of beta2-ARs (with
      zinterol/CGP20712A) produced little contractile response in control cells but
      pronounced inotropic and lusitropic responses in cells treated with the
      cholesterol-depleting agent methyl-beta-cyclodextrin (MBCD). This was not linked
      to modulation of L-type Ca(2+) current, but instead to a discrete PKA-mediated
      phosphorylation of phospholamban at Ser(16). Application of a cell-permeable
      inhibitor of caveolin-3 scaffolding interactions mimicked the effect of MBCD on
      phosphorylated phospholamban (pPLB) during beta2-AR stimulation, consistent with
      MBCD acting via caveolae. Biosensor experiments revealed beta2-AR mobilisation of
      cAMP in PKA II signalling domains of intact cells only after MBCD treatment,
      providing a real-time demonstration of cAMP freed from caveolar constraint. Other
      proteins have roles in compartmentation, so the effects of phosphodiesterase
      (PDE), protein phosphatase (PP) and phosphoinositide-3-kinase (PI3K) inhibitors
      on pPLB and contraction were compared in control and MBCD treated cells. PP
      inhibition alone was conspicuous in showing robust de-compartmentation of beta2
      AR-derived signalling in control cells and a comparatively diminutive effect
      after cholesterol depletion. Collating all evidence, we promote the novel concept
      that caveolae limit beta2-AR-cAMP signalling by providing a platform that not
      only attenuates production of cAMP but also prevents inhibitory modulation of PPs
      at the sarcoplasmic reticulum. This article is part of a Special Issue entitled
      "Local Signaling in Myocytes".

PMID- 21740912
TI  - Thermodynamics and kinetics of the hairpin ribozyme from atomistic
      folding/unfolding simulations.
AB  - We report a set of atomistic folding/unfolding simulations for the hairpin
      ribozyme using a Monte Carlo algorithm. The hairpin ribozyme folds in solution
      and catalyzes self-cleavage or ligation via a specific two-domain structure. The
      minimal active ribozyme has been studied extensively, showing stabilization of
      the active structure by cations and dynamic motion of the active structure. Here,
      we introduce a simple model of tertiary-structure formation that leads to a phase
      diagram for the RNA as a function of temperature and tertiary-structure strength.
      We then employ this model to capture many folding/unfolding events and to examine
      the transition-state ensemble (TSE) of the RNA during folding to its active
      "docked" conformation. The TSE is compact but with few tertiary interactions
      formed, in agreement with single-molecule dynamics experiments. To compare with
      experimental kinetic parameters, we introduce a novel method to benchmark Monte
      Carlo kinetic parameters to docking/undocking rates collected over many single
      molecular trajectories. We find that topology alone, as encoded in a biased
      potential that discriminates between secondary and tertiary interactions, is
      sufficient to predict the thermodynamic behavior and kinetic folding pathway of
      the hairpin ribozyme. This method should be useful in predicting folding
      transition states for many natural or man-made RNA tertiary structures.

PMID- 21740913
TI  - A myristoyl/phosphoserine switch controls cAMP-dependent protein kinase
      association to membranes.
AB  - The cAMP-dependent protein kinase [protein kinase A (PKA)] mediates a myriad of
      cellular signaling events, and its activity is tightly regulated in both space
      and time. Among these regulatory mechanisms is N-myristoylation, whose biological
      role has been elusive. Using a combination of thermodynamics, kinetics, and
      spectroscopic methods, we analyzed the effects of N-myristoylation and
      phosphorylation at Ser10 on the interactions of PKA with model membranes. We
      found that, in the absence of lipids, the myristoyl group is tucked into the
      hydrophobic binding pocket of the enzyme (myr-in state). Upon association with
      lipid bilayers, the myristoyl group is extruded and inserts into the hydrocarbon
      region of the lipid bilayer (myr-out state). NMR data indicate that the enzyme
      undergoes conformational equilibrium between myr-in and myr-out states, which can
      be shifted byeither interaction with membranes and/or phosphorylation at Ser10.
      Our results provide evidence that the membrane binding motif of the myristoylated
      C-subunit of PKA (PKA-C) steers the enzyme toward lipids independent of its
      regulatory subunit or an A-kinase anchoring protein, providing an additional
      mechanism to localize the enzyme near membrane-bound substrates.

PMID- 21740914
TI  - A discrete event system specification (DEVS)-based model of consanguinity.
AB  - Consanguinity or inter-cousin marriage is a phenomenon quite prevalent in certain
      regions around the globe. Consanguineous parents have a higher risk of having
      offspring with congenital disorders. It is difficult to model large scale
      consanguineous parental populations because of disparate cultural issues unique
      to regions and cultures across the globe. Although consanguinity has previously
      been studied as a social problem, it has not been modeled from a biological
      perspective. Discrete event system specification (DEVS) is a powerful modeling
      formalism for the study of intricate details of real-world complex systems. In
      this paper, we have developed a DEVS model to get an insight into the role of
      consanguineous marriages in the evolution of congenital disorders in a
      population. As proof-of-concept, we further developed a consanguinity simulation
      model in Simio simulation software. Simulation results validated using population
      growth data show the effectiveness of this approach in the modeling of
      consanguinity in populations.

PMID- 21740915
TI  - Co-dominance and succession in forest dynamics: the role of interspecific
      differences in crown transmissivity.
AB  - Forests that are composed of two or more tree species with similar ecological
      strategies appear to contradict the competitive exclusion principle. Beech-maple
      communities are a well-known example of such a system. On a local scale, a number
      of mechanisms have been proposed to explain the coexistence of these two species.
      These are reciprocal replacement, external factors that favour alternatively one
      or the other species and demographic stochasticity. This paper presents and
      analyses a simple mathematical model that shows that external factors are not an
      essential requirement for coexistence. Rather, coexistence requires interspecific
      differences in light transmissivity through the crowns of adult trees. However,
      all the three mechanisms mentioned above can be interpreted within the framework
      of the model. Furthermore, many models of forest dynamics make use of shade
      tolerance as a key feature in describing successional dynamics. Despite its
      importance, however, shade tolerance does not have a commonly accepted
      quantitative definition. Here, a simple scheme is proposed where the relationship
      between shade tolerance, individual traits (growth and survival) and successional
      status is defined. This might have important implications in understanding the
      overall dynamics. Theoretical results have been compared with a number of studies
      carried out in North American forests. In particular, coexistence in beech-maple
      communities and the relation between shade tolerance and successional status in a
      beech-hemlock-birch community have been discussed.

PMID- 21740916
TI  - An upper-body can improve the stability and efficiency of passive dynamic
      walking.
AB  - The compass-gait walker proposed by McGeer can walk down a shallow slope with a
      self-stabilizing gait that requires no actuation or control. However, as the
      slope goes to zero so does the walking speed, and dynamic gait stability is only
      possible over a very narrow range of slopes. Gomes and Ruina have results
      demonstrating that by adding a torso to the compass-gait walker, it can walk
      passively on level-ground with a non-infinitesimal constant average speed.
      However, the gait involves exaggerated joint movements, and for energetic reasons
      horizontal passive dynamic walking cannot be stable. We show in this research
      that in addition to collision-free walking, adding a torso improves stability and
      walking speed when walking downhill. Furthermore, adding arms to the torso
      results in a collision-free periodic gait with natural-looking torso and limb
      movements. Overall, in contrast to the suggestions that active control may be
      needed to balance an upper-body on legs, it turns out that the upper and lower
      bodies can be integrated to improve the stability, efficiency and speed of a
      passive dynamic walker.

PMID- 21740917
TI  - Dynamics of an SIQS epidemic model with transport-related infection and exit
      entry screenings.
AB  - Population dispersal, as a common phenomenon in human society, may cause the
      spreading of many diseases such as influenza, SARS, etc. which are easily
      transmitted from one region to other regions. Exit and entry screenings at the
      border are considered as effective ways for controlling the spread of disease. In
      this paper, the dynamics of an SIQS model are analyzed and the combined effects
      of transport-related infection enhancing and exit-entry screenings suppressing on
      disease spread are discussed. The basic reproduction number is computed and
      proved to be a threshold for disease control. If it is not greater than the
      unity, the disease free equilibrium is globally asymptotically stable. And there
      exists an endemic equilibrium which is locally asymptotically stable if the
      reproduction number is greater than unity. It is shown that the disease is
      endemic in the sense of permanence if and only if the endemic equilibrium exists.
      Exit screening and entry screening are shown to be helpful for disease
      eradication since they can always have the possibility to eradicate the disease
      endemic led by transport-related infection and furthermore have the possibility
      to eradicate disease even when the isolated cites are disease endemic.

PMID- 21740918
TI  - TREK-1 isoforms generated by alternative translation initiation display different
      susceptibility to the antidepressant fluoxetine.
AB  - Two-pore-domain K(+) (K(2)P) channels are highly expressed in neurons and cardiac
      myocytes. In this study we investigated the potency of the antidepressant
      fluoxetine to inhibit brain and cardiac K(2)P channels, TREK-1, TASK-1 and THIK
      1. Maximal sensitivity was detected for TREK-1, which was inhibited by 77% when
      expressed in HEK-293 cells and Xenopus oocytes. Alternative translation
      initiation (ATI) generates two different protein products from a single
      transcript of TREK-1. Electrophysiological analysis of two polypeptides
      engineered by mutagenesis (TREK-1[M53I], TREK-1[DeltaN52]) revealed reduced
      current amplitude and K(+) selectivity of the truncated TREK-1 isoform. The
      sensitivity of TREK-1[DeltaN52] to fluoxetine decreased by 70%, indicating that
      the first 52 amino acids are essential for TREK-1 sensitivity to this drug.

PMID- 21740919
TI  - The role of 5-HT1A receptors in fish oil-mediated increased BDNF expression in
      the rat hippocampus and cortex: a possible antidepressant mechanism.
AB  - Epidemiological and dietary studies show that nutritional deficit of omega-3
      polyunsaturated fatty acids (omega-3 PUFA) is directly related to the prevalence
      and severity of depression. Supplementation with docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA) during critical periods of development (pregnancy and
      lactation) is essential for cortical maturation, synaptogenesis and myelination,
      and may also mitigate the risk for cognitive deficits and psychopathologies in
      young adults. The present study was performed to evaluate the involvement of
      serotonin (5-HT) receptors, particularly of 5-HT(1A), and hippocampal brain
      derived neurotrophic factor (BDNF) expression in the antidepressant effect of
      omega-3 PUFA supplementation. In Experiment 1, the antidepressant effects of fish
      oil were assessed by the modified forced swim test in adult rats. The data
      indicated a robust antidepressant effect produced by this supplementation and
      that treatment of the rats with WAY 100135 reversed this effect. In Experiment 2,
      cortical and hippocampal contents of BDNF, 5-HT, dopamine (DA) and its
      metabolites, 5-hydroxyindoleacetic acid (5-HIAA), and 3,4-dihydroxyphenylacetic
      acid (DOPAC), were determined in animals subjected to the same protocol.
      Increased BDNF expression in the cortex and hippocampus of both age groups was
      detected. In 90 day-old rats, 5-HT content in the hippocampus was increased,
      whereas 5-HIAA formation was diminished in the fish oil group. We suggest the
      occurrence of a reciprocal involvement of 5-HT(1A) receptors activation and the
      hippocampal BDNF-increased expression mediated by fish oil supplementation. These
      data corroborate and expand the notion that supplementation with omega-3 PUFA
      produces antidepressant effects mediated by an increase in serotonergic
      neurotransmission, particularly in the hippocampus. This article is part of a
      Special Issue entitled 'Anxiety and Depression'.

PMID- 21740920
TI  - Stress-induced activation of the brainstem Bcl-xL gene expression in rats treated
      with fluoxetine: correlations with serotonin metabolism and depressive-like
      behavior.
AB  - Mechanisms underlying stress-induced depression and antidepressant drug action
      were shown to involve alterations in serotonergic (5-HT) neurotransmission and
      expression of genes coding for proteins associated with neurotrophic signaling
      pathways and cell-survival in the hippocampus and cortex. Expression of these
      genes in the brainstem containing 5-HT neurons may also be related to
      vulnerability or resilience to stress-related psychopathology. Here we
      investigated 5-HT markers and expression of genes for Brain-Derived Neurotrophic
      Factor (BDNF) and apoptotic proteins in the brainstem in relation to swim stress
      induced behavioral despair. We found that anti-apoptotic Bcl-xL gene is sensitive
      to stress during the course of fluoxetine administration. Responsiveness of this
      gene to stress appeared concomitantly with an antidepressant-like effect of
      fluoxetine in the forced swim test. Bcl-xL transcript levels showed negative
      correlations with duration of immobility in the test and 5-HT turnover in the
      brainstem. In contrast, BDNF and pro-apoptotic protein Bax mRNA levels were
      unchanged by either fluoxetine or stress, suggesting specificity of Bcl-xL gene
      responses to these treatments. We also found that the levels of mRNAs for
      tryptophan hydroxylase-2 (TPH2) and 5-HT transporter (5-HTT) were significantly
      down-regulated following prolonged treatment with fluoxetine, but were not
      affected by stress. Unlike TPH2 and 5-HTT, 5-HT1A receptor mRNA levels were not
      altered by fluoxetine but significantly increased in response to swim stress.
      These data show that long-term fluoxetine treatment leads to changes in 5-HT and
      Bcl-xL responses to stress associated with antidepressant-like effects of the
      drug. This article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21740921
TI  - Characterization of voltage-dependent calcium channel blocking peptides from the
      venom of the tarantula Grammostola rosea.
AB  - Voltage-dependent calcium channel blocking peptides were purified and sequenced
      from the venom of the tarantula, Grammostola rosea. cDNAs encoding the peptide
      sequences were cloned from the venom gland cDNA library. The electrophysiological
      effects of the peptides on several types of voltage-dependent calcium channels
      were evaluated using a Xenopus laevis oocyte expression system. A peptide
      contained in one of the HPLC peak fractions inhibited P/Q type voltage-dependent
      calcium channels (Ca(v)2.1). The amino acid sequence of this peptide is identical
      to that of omega-grammotoxin SIA. A peptide from another discrete peak, which is
      identical to GsAFII except for one tryptophan residue in the C-terminus,
      inhibited L-type voltage-dependent calcium channels (Ca(v)1.2). A novel peptide,
      named GTx1-15 (Accession number, AB201016), shows 76.5% sequence homology with
      the sodium channel blocker phrixotoxin 3, however, GTx1-15 preferentially
      inhibited T-type voltage-dependent calcium channels (Ca(v)3.1). In silico
      secondary and tertiary structure prediction revealed that GTx1-15 and sodium
      channel blockers such as hainantoxin-IV, phrixotoxin 3, and ceratotoxin 2 show
      very similar beta-strand composition, distribution of Optimal Docking Areas
      (continuous surface patches likely to be involved in protein-protein
      interactions), and surface electrostatic potential. These findings suggest that
      these peptide toxins evolved from common ancestors by gene duplication to
      maintain surface atmospheres appropriate for interaction with low-voltage
      dependent ion channels.

PMID- 21740922
TI  - A genome-wide association study confirms APOE as the major gene influencing
      survival in long-lived individuals.
AB  - We conducted a case-control genome-wide association study (GWAS) of human
      longevity, comparing 664,472 autosomal SNPs in 763 long-lived individuals (LLI;
      mean age: 99.7 years) and 1085 controls (mean age: 60.2 years) from Germany. Only
      one association, namely that of SNP rs4420638 near the APOC1 gene, achieved
      genome-wide significance (allele-based P=1.8*10(-10)). However, logistic
      regression analysis revealed that this association, which was replicated in an
      independent German sample, is fully explicable by linkage disequilibrium with the
      APOE allele E4, the only variant hitherto established as a major genetic
      determinant of survival into old age. Our GWAS failed to identify any additional
      autosomal susceptibility genes. One explanation for this lack of success in our
      study would be that GWAS provide only limited statistical power for a polygenic
      phenotype with loci of small effect such as human longevity. A recent GWAS in
      Dutch LLI independently confirmed the APOE-longevity association, thus
      strengthening the conclusion that this locus is a very, if not the most,
      important genetic factor influencing longevity.

PMID- 21740923
TI  - Coupling biomechanics to a cellular level model: an approach to patient-specific
      image driven multi-scale and multi-physics tumor simulation.
AB  - Modeling of tumor growth has been performed according to various approaches
      addressing different biocomplexity levels and spatiotemporal scales. Mathematical
      treatments range from partial differential equation based diffusion models to
      rule-based cellular level simulators, aiming at both improving our quantitative
      understanding of the underlying biological processes and, in the mid- and long
      term, constructing reliable multi-scale predictive platforms to support patient
      individualized treatment planning and optimization. The aim of this paper is to
      establish a multi-scale and multi-physics approach to tumor modeling taking into
      account both the cellular and the macroscopic mechanical level. Therefore, an
      already developed biomodel of clinical tumor growth and response to treatment is
      self-consistently coupled with a biomechanical model. Results are presented for
      the free growth case of the imageable component of an initially point-like
      glioblastoma multiforme tumor. The composite model leads to significant tumor
      shape corrections that are achieved through the utilization of environmental
      pressure information and the application of biomechanical principles. Using the
      ratio of smallest to largest moment of inertia of the tumor material to quantify
      the effect of our coupled approach, we have found a tumor shape correction of 20%
      by coupling biomechanics to the cellular simulator as compared to a cellular
      simulation without preferred growth directions. We conclude that the integration
      of the two models provides additional morphological insight into realistic tumor
      growth behavior. Therefore, it might be used for the development of an advanced
      oncosimulator focusing on tumor types for which morphology plays an important
      role in surgical and/or radio-therapeutic treatment planning.

PMID- 21740924
TI  - Fatty acid amide hydrolase blockade attenuates the development of collagen
      induced arthritis and related thermal hyperalgesia in mice.
AB  - Fatty acid amide hydrolase (FAAH) is the primary degradative enzyme of the
      endocannabinoid anandamide (N-arachidonoylethanolamine), which activates
      cannabinoid CB(1) and CB(2) receptors. FAAH disruption reduces nociception in a
      variety of acute rodent models of inflammatory pain. The present study
      investigated whether these actions extend to the chronic, collagen-induced
      arthritis (CIA) model. We investigated the anti-arthritic and anti-hyperalgesic
      effects of genetic deletion or pharmacological inhibition of FAAH in the CIA
      model. FAAH (-/-) mice, and FAAH-NS mice that express FAAH exclusively in nervous
      tissue, displayed decreased severity of CIA and associated hyperalgesia. These
      phenotypic anti-arthritic effects were prevented by repeated daily injections of
      the CB(2) receptor antagonist, SR144528, but not the CB(1) receptor antagonist
      rimonabant. Similarly, repeated administration of the FAAH inhibitor URB597
      reduced CIA severity, and acute administration of rimonabant, but not SR144528,
      blocked the anti-hyperalgesic effects of prolonged FAAH inhibition, suggesting
      that prolonged CB(2) receptor activation reduces the severity of CIA, whereas
      acute CB(1) receptor activation reduces CIA-induced hyperalgesia. In contrast,
      acute administration of URB597 elicited a CB(1) receptor-dependent anti
      hyperalgesic effect. The observed anti-arthritic and anti-hyperalgesic properties
      of FAAH inhibition, coupled with a lack of apparent behavioral alterations,
      suggest that endocannabinoid modulating enzymes offer a promising therapeutic
      target for the development of novel pharmacological approaches to treat
      rheumatoid arthritis and associated hyperalgesia.

PMID- 21740925
TI  - Cytosolic thioredoxin from Ruditapes philippinarum: molecular cloning,
      characterization, expression and DNA protection activity of the recombinant
      protein.
AB  - Thioredoxin (TRx) is a small redox protein that plays significant roles in
      protection against oxidative stress and in cell homeostasis by maintaining
      oxidized proteins in a reduced state. Here, we describe the isolation and
      characterization of a full-length TRx cDNA sequence from manila clam, Ruditapes
      philippinarum and named it as RpTRx. The full length sequence consists of 1416 bp
      with an open reading frame of 318 bp encoding for 106 amino acids. RpTRx protein
      harbors evolutionarily-conserved TRx active site (32)WCGPC(36). Phylogenetic
      analysis revealed a close proximity of RpTRx with the orthologue in Japanese
      scallop, Chlamys farreri. RpTRx was found to be constitutively expressed in
      hemocyte, gill, mantle, foot and siphon indicating a general role in
      physiological processes in various tissues. With regard to a potential role in
      immune responses, the RpTRx mRNA was found to be up-regulated in hemocytes after
      bacterial (Vibrio tapetis) and lipopolysaccharide (LPS) challenge at 3h post
      infection (p.i.); a wavering increase was observed up to 96 h p.i. for LPS
      challenge and 48 h p.i. for bacterial challenge. Thus, RpTRx may function as an
      intracellular antioxidant to protect the cells against ROS induced by LPS and
      bacterial challenges. Indeed, when recombinant RpTRx protein (rRpTRx) was over
      expressed in Escherichiacoli Rosetta gami(TM) (DE3) cells, it was able to
      scavenge free radicals and protect super-coiled DNA from oxidative damage induced
      by a metal-ion catalyzed oxidation reaction. In summary, RpTRx plays an essential
      role in cellular defense and maintenance of homeostasis in the manila clam.

PMID- 21740926
TI  - Role of Penaeus monodon Kruppel-like factor (PmKLF) in infection by white spot
      syndrome virus.
AB  - Sp1-like proteins and Kruppel-like factors (KLFs) are highly related zinc-finger
      proteins that have crucial roles in transcription. One expressed sequence tag
      (EST, HPA-N-S01-EST0038) from shrimps is homologous to Sp1. This study reports
      the cloning and characteristics of a KLF from shrimp, Penaeus monodon (PmKLF).
      The full-length PmKLF cDNA is 1702 bp, encoding a polypeptide of 360 amino acids.
      Sequence analysis revealed that the sequence of PmKLF is similar to that of KLF11
      in humans, mice and zebrafish. RT-PCR analysis indicated that PmKLF mRNA is
      expressed in all examined tissues. Additionally, immunofluorescence analysis
      revealed that GFP-KLF fusion protein is located in the nucleus as dots in an
      insect cell line, Sf9. Localization of PmKLF in the nucleus is also observed in
      the hemolymph from white spot syndrome virus (WSSV)-infected and WSSV-uninfected
      Litopenaeus vannamei. Knockdown of the expression of PmKLF transcript in WSSV
      infected shrimp resulted in delayed cumulative mortalities, suggesting that PmKLF
      is important to WSSV infection. Moreover, inhibition of PmKLF expression reduced
      the copy number of WSSV and ie1 expression, revealing that PmKLF affects WSSV
      infection via interfering with ie1 expression.

PMID- 21740927
TI  - Chlorination byproducts induce gender specific autistic-like behaviors in CD-1
      mice.
AB  - In 2000, the Agency for Toxic Substances and Disease Registry (ATSDR) released a
      report concerning elevated autism prevalence and the presence water chlorination
      byproducts in the municipal drinking water supply in Brick Township, New Jersey.
      The ATSDR concluded that it was unlikely that these chemicals, specifically
      chloroform, bromoform (Trihalomethanes; THMs) and tetrachloroethylene
      (Perchloroethylene; PCE) had contributed to the prevalence of autism in this
      community based upon correlations between timing of exposure and/or concentration
      of exposure. The ATSDR conclusion may have been premature, as there is no
      conclusive data evidencing a correlation between a particular developmental time
      point that would render an individual most susceptible to toxicological insult
      with the development of autism. Therefore, it was our aim to determine if these
      chemicals could contribute to autistic like behaviors. We found that males
      treated with THMs and PCE have a significant reduction in the number of
      ultrasonic vocalizations (USVs) emitted in response to maternal separation, which
      are not attributed to deficits in vocal ability to or to lesser maternal care.
      These same males also show significantly elevated anxiety, an increase in
      perseverance behavior and a significant reduction in sociability. The sum of our
      data suggests that male, but not female mice, develop autistic like behaviors
      after gestational and postnatal exposure to the aforementioned chemical triad via
      drinking water. We believe development of such aberrant behaviors likely involves
      GABAergic system development.

PMID- 21740928
TI  - Altered striatal dopamine release following a sub-acute exposure to manganese.
AB  - Certain metals that are necessary for regulating biological function at trace
      levels hold the potential to become neurotoxic when in excess. Specifically,
      chronic exposure to high levels of manganese leads to manganism, a neurological
      disorder that exhibits both motor and learning deficits similar to Parkinson's
      disease. Since Parkinson's disease symptomatology is primarily attributed to
      dopamine neurodegeneration in the striatum, dopamine system dysfunction has been
      implicated in the onset of manganism. In this study, dopamine system function in
      the dorsal striatum was evaluated in C57Bl/6 mice, 1, 7, and 21 days following
      repeated injections of manganese(II) chloride (50 mg/kg, subcutaneous)
      intermittently for 7 days. Tissue content analysis confirmed the presence of
      persistent accumulation of manganese in the striatum up to 21 days after
      cessation of treatment. In vitro fast scan cyclic voltammetry examined the effect
      of sub-acute manganese on electrically stimulated dopamine release and uptake in
      the striatum. While no difference was observed in uptake rates following
      manganese treatment, dopamine release was attenuated on days 7 and 21, compared
      to control levels. Basal levels of extracellular dopamine determined by the zero
      net flux microdialysis method were significantly lower in manganese-treated mice
      at 7 days post-treatment. On the other hand, potassium stimulated increases in
      extracellular dopamine were attenuated at all three time points. Together, these
      findings indicate that repeated manganese exposure has long-term effects on the
      regulation of exocytotic dopamine release in the striatum, which may be involved
      in the mechanism underlying manganese toxicity.

PMID- 21740929
TI  - Axonal fluorescence quantitation provides a new approach to assess cutaneous
      innervation.
AB  - We present a novel approach to quantify skin innervation by measuring the PGP 9.5
      immunoreactive (PGP-ir) fluorescence corresponding to axons within the epidermis
      and dermis. The skin biopsies from 35 controls and 45 small fiber neuropathy
      (SFN) patients were included. In 50-MUm free-floating sections, we determined the
      intraepidermal nerve fiber density (IENFD) by direct fluorescence visualization
      and captured 2-MUm thick individual optical sections using the same confocal
      microscope and magnification. We measured the fluorescence of the PGP-ir axons in
      both, epidermal and dermal area by using the ImageJ software. There was good
      interobserver and intraobserver reliability of PGP-ir measures, similar than for
      IENFD. The PGP-ir axons were found decreased in patients with SFN (1.10/00 and
      9.00/00 respectively for epidermal and dermal area in contrast to 2.20/00 and
      16.00/00, respectively to controls). The area under the ROC curve was 0.90 for
      the IENFD, 0.84 for epidermal PGP-ir axons and 0.70 for dermal PGP-ir axons.
      There was a positive correlation between the IENFD and the PGP-ir axons at
      epidermis (Spearman Rho=0.66, p<0.001) as well as for the dermal nerve length and
      the PGP-ir axons at dermis (Spearman Rho=0.45, p<0.05). This method is also
      particularly adequate for the quantitation of dermal nerve fibers. We conclude
      that quantifying the fluorescent PGP-ir axons could help to assess skin
      innervation (dermal and epidermal nerve fibers) in patients with SFN.

PMID- 21740930
TI  - Psychological distress, depressive symptoms, and cellular immunity among healthy
      individuals: a 1-year prospective study.
AB  - Cross-sectional and case-control studies have reported that psychological
      distress and depression are associated with reduced cellular immune competence
      but the directionality of the relationship remains uncertain. This study
      investigated whether levels of psychological distress and depressive symptoms are
      related to subsequent changes in counts of lymphocyte subsets (natural killer
      (NK), B, and T cell) and/or whether changes of immune markers predict
      psychological distress/depressive symptoms in a 1-year prospective study design.
      A total of 105 healthy employees (67 men and 38 women), aged 23-59 (mean 40)
      years with an average of 15years of education, underwent a blood draw for the
      measurement of circulating immune cells and completed the Japanese version of the
      28-item General Health Questionnaire (GHQ-28) and the Center for Epidemiologic
      Studies Depression Scale (CES-D) in April 2002 (time 1) and 2003 (time 2).
      Hierarchical multiple linear regression analyses revealed that GHQ-28 and CES-D
      scores at time 1 were significantly (p<.05) and inversely associated with NK
      cells at time 2 controlling for potential confounders including time 1 NK cells
      (beta=-.221 and -.177, respectively). In contrast, NK cells and NK cell
      cytotoxicity at time 1 did not predict GHQ-28 or CES-D score at time 2
      controlling for GHQ-28/CES-D score at time 1. GHQ-28 and CES-D scores were not
      related to T or B cells at times 1 and 2. The present findings indicate that
      psychological distress and depressive symptoms may precede and predict
      suppression of NK cell immunity while NK cells did not lead to subsequent
      psychological distress and depressive symptoms, suggesting an absence of the bi
      directional relationships.

PMID- 21740931
TI  - Neurophysiology of Hungarian subject-verb dependencies with varying intervening
      complexity.
AB  - Non-adjacent dependencies are thought to be more costly to process than sentences
      wherein dependents immediately follow or precede what they depend on. In English
      locality effects have been revealed, while in languages with rich case marking
      (German and Hindi) sentence final structures show anti-locality-effects. The
      motivation of the current study is to test whether locality effects can be
      directly applied to a typologically different language than those investigated so
      far. Hungarian is a "topic prominent" language; it permits a variation of
      possible word sequencing for semantic reasons, including SVO word order.
      Hungarian also has a rich morphological system (e.g., rich case system) and
      postpositions to indicate grammatical functions. In the present ERP study,
      Hungarian subject-verb dependencies were compared by manipulating the mismatch of
      number agreement between the sentence's initial noun phrase and the sentence's
      final intransitive verb as well as the complexity of the intervening sentence
      material, interrupting the dependencies. Possible lexical class and frequency or
      cloze-probability effects for the first two words of the intervening sentence
      material were revealed when used separate baseline for each word, while at the
      third word of the intervening material as well as at the main verb ERPs were not
      modulated by complexity but at the verb ERPs were enhanced by grammaticality.
      Ungrammatical sentences enlarged the amplitude of both LAN and P600 components at
      the main verb. These results are in line with studies suggesting that the
      retrieval of the first element of a dependency is not influenced by distance from
      the second element, as the first element is directly accessible when needed for
      integration (e.g., McElree, 2000).

PMID- 21740932
TI  - Alterations of glucose metabolism in Escherichia coli mutants defective in
      respiratory-chain enzymes.
AB  - The effects of reduced efficiency of proton-motive force (pmf) generation on
      glucose metabolism were investigated in Escherichia coli respiratory-chain
      mutants. The respiratory chain of E. coli consists of two NADH dehydrogenases and
      three terminal oxidases, all with different abilities to generate a pmf. The
      genes for isozymes with the highest pmf-generating capacity (NADH dehydrogenase-1
      and cytochrome bo3 oxidase) were knocked out singly or in combination, using a
      wild-type strain as the parent. Analyses of glucose metabolism by jar
      fermentation revealed that the glucose consumption rate per cell increased with
      decreasing efficiency of pmf generation, as determined from the growth parameters
      of the mutants. The highest rate of glucose metabolism was observed in the double
      mutant, and the lowest was observed in the wild-type strain. The respiration
      rates of the single-knockout mutants were comparable to that of the wild-type
      strain, and that of the double mutant was higher, apparently as a result of the
      upregulation of the remaining respiratory chain enzymes. All of the strains
      excreted 2-oxoglutaric acid as a product of glucose metabolism. Additionally, all
      of the mutants excreted pyruvic acid and/or acetic acid. Interestingly, the
      double mutant excreted L-glutamic acid. Alterations of the fermentation profiles
      provide clues regarding the metabolic regulation in each mutant.

PMID- 21740933
TI  - The recovery of polyphenols from olive mill waste using two adsorbing vegetable
      matrices.
AB  - Olive mill wastewater (OMW) is considered one of the most pollutive waste
      materials in the Mediterranean basin. However, its phenolic fraction should be
      recovered, since it has been shown to have incredible benefits for health. In the
      present study, the adsorbent and desorbent capacities of Azolla and granular
      activated carbon (GAC) were investigated. The GAC was found to be more efficient
      than Azolla in both the adsorption and the desorption of phenols. The total
      characterization of two powder products obtained from Azolla and GAC desorption
      is reported, together with their antioxidant and antiradical activities. In the
      Azolla powder product, total polyphenols were more than twice as numerous as
      those found in the GAC powder product. The GAC powder contained hydroxytyrosol in
      concentrations that were 3.5 times higher than those of Azolla. On the other
      hand, both powder products showed great antiradical activities: the IC50 was
      found to be 102 mg ml-1 for the Azolla and 199 mg ml-1 for the GAC powders
      respectively. The oxygen radical absorbance capacity was very high: 4097 MUmol TE
      g-1 Azolla powder product and 1277 MUmol TE g-1 of GAC powder products.

PMID- 21740934
TI  - Reducing agents improve enzymatic hydrolysis of cellulosic substrates in the
      presence of pretreatment liquid.
AB  - Enzymatic hydrolysis of pretreated lignocellulosic substrates has emerged as an
      interesting option to produce sugars that can be converted to liquid biofuels and
      other commodities using microbial biocatalysts. Lignocellulosic substrates are
      pretreated to make them more accessible to cellulolytic enzymes, but the
      pretreatment liquid partially inhibits subsequent enzymatic hydrolysis. The
      presence of pretreatment liquid from Norway spruce resulted in a 63% decrease in
      the enzymatic saccharification of Avicel compared to when the reaction was
      performed in a buffered aqueous solution. The addition of 15mM of a reducing
      agent (hydrogen sulfite, dithionite, or dithiothreitol) to reaction mixtures with
      the pretreatment liquid resulted in up to 54% improvement of the saccharification
      efficiency. When the reducing agents were added to reaction mixtures without
      pretreatment liquid, there was a 13-39% decrease in saccharification efficiency.
      In the presence of pretreatment liquid, the addition of 15mM dithionite to
      Avicel, alpha-cellulose or filter cake of pretreated spruce wood resulted in
      improvements between 25 and 33%. Positive effects (6-17%) of reducing agents were
      also observed in experiments with carboxymethyl cellulose and 2-hydroxyethyl
      cellulose. The approach to add reducing agents appears useful for facilitating
      the utilization of enzymes to convert cellulosic substrates in industrial
      processes.

PMID- 21740935
TI  - Genetic characterization of K13965, a strain of Oak Vale virus from Western
      Australia.
AB  - K13965, an uncharacterized virus, was isolated in 1993 from Anopheles annulipes
      mosquitoes collected in the Kimberley region of northern Western Australia. Here,
      we report its genomic sequence, identify it as a rhabdovirus, and characterize
      its phylogenetic relationships. The genome comprises a P' (C) and SH protein
      similar to the recently characterized Tupaia and Durham viruses, and shows
      overlap between G and L genes. Comparison of K13965 genome sequence to other
      rhabdoviruses identified K13965 as a strain of the unclassified Australian Oak
      Vale rhabdovirus, whose complete genome sequence we also determined. Phylogenetic
      analysis of N and L sequences indicated genetic relationship to a recently
      proposed Sandjima virus clade, although the Oak Vale virus sequences form a
      branch separate from the African members of that group.

PMID- 21740936
TI  - Genomic analysis of four human metapneumovirus prototypes.
AB  - Human metapneumovirus (HMPV) is an important cause of acute respiratory illness
      in children. We determined the complete genome sequence of four strains of HMPV
      representing each of the four lineages. These sequences were compared with
      published HMPV genome sequences. Most genes were conserved between the genetic
      lineages (79.5-99.6%), though nucleotide diversity was greater than amino acid
      diversity, suggesting functional constraints on mutation. However, the SH and G
      open reading frames were more variable (mean 76.4% and 59.0% aa identity,
      respectively), with mostly nonsynonymous changes, suggesting selective pressure
      on the SH and G proteins. Gene-start regions were largely conserved between genes
      and viruses, while gene-end sequences were conserved between viruses but not
      between genes. The SH-G and G-L intergenic regions were extremely long (~200 nt)
      and have no defined function, yet were highly conserved within major groups.
      These findings highlight broadly conserved regions of the HMPV genome and suggest
      unidentified biological roles for SH and G.

PMID- 21740937
TI  - Construction and characterization of human adenovirus serotype 3 packaged by
      serotype 7 hexon.
AB  - Human adenovirus serotype 3 (Ad3) and serotype 7 (Ad7) are important pathogens
      causing respiratory tract diseases such as acute respiratory disease in pediatric
      and adult patients, but the immunodominant targets of Ad3- and Ad7-specific
      neutralizing antibodies (NAbs) remain unclear. A chimeric Ad vector, Ad3/H7, was
      constructed by replacing the Ad3 hexon gene (H3) with the hexon gene (H7) of Ad7.
      The chimeric viruses were successfully rescued in HEp-2 cells, and the Ad7 hexon
      was able to encapsidate the Ad3 genome, and functioned as efficiently as the Ad3
      hexon. Furthermore, we tested the host neutralization responses against the
      viruses using BALB/C mice. Up to 97% of the NAbs produced by mice that were
      infected with these viruses were specific for the hexon protein in vitro.
      Preimmunization of mice with one of Ad7 and Ad3/H7 significantly prevented
      subsequent intranasal infection of the other type in vivo. In contrast,
      preimmunization of mice with one of Ad3 and Ad3/H7 did not remarkably prevent
      subsequent infection of the other type. We next evaluated the functional
      significance of hexon and other structural proteins specific NAbs to suppress the
      immunogenicity of Ad3/H3 and Ad3/H7 vectors expressing EGFP in mice preimmunized
      with wild type Ad. Preimmunization of mice with Ad7 evidently suppressed EGFP
      specific humoral immune responses elicited by Ad3/H7, and did not exert
      suppressive effects on Ad3/H3. But contrary to the in vitro neutralization
      results, EGFP-specific humoral immune responses elicited by Ad3/H7 was remarkably
      inhibited in Ad3-preimmunization mice. The whole genome of the Ad7 strain was
      sequenced and aligned with Ad3. The major differences between Ad3 and Ad7 were
      only observed in the fiber and hexon among all structural proteins, and the
      variation between the hexons only located in four hypervariable regions (HVRs),
      HVR-1, -2, -5, and -7. These results thus suggest that Ad3- and Ad7-specific NAbs
      are directed primarily against the hexon proteins both in vitro and in vivo. But
      high titer Ad3 fiber-specific NAbs may also play an important role in blunting
      Ad3 immunogenicity in vivo. These studies contribute to a more profound
      understanding of Ad immunogenicity and have relevance for the design of novel Ad
      vaccine.

PMID- 21740939
TI  - Pre-treatment prediction of response to pegylated-interferon plus ribavarin for
      chronic hepatitis C using RVR.

PMID- 21740941
TI  - The role of child temperament in parental child feeding practices and attitudes
      using a sibling design.
AB  - Although previous research indicates that parental child feeding practices are
      one component of a bidirectional relationship between children and parents,
      little is known about how child temperament operates in this relationship. The
      purpose of this study was to investigate relationships between child temperament
      and parental feeding practices and attitudes using a sibling design. By
      collecting data regarding pairs of siblings, we were able to investigate sibling
      differences and differential parental treatment. We examined mothers' and
      fathers' perceptions of their two children's temperaments as well as reports of
      the feeding practices and attitudes they use with each child. Fifty-five mothers
      and fathers completed questionnaires including the Carey Temperament Scales and
      the Child Feeding Questionnaire (CFQ). Results from correlation analyses showed
      that 6 of the 9 father reports of temperament between two siblings were
      positively related, whereas 1 of the 9 mother reports were positively related.
      Mothers' and fathers' perceptions of temperament were positively correlated for a
      single child. Some patterns were found between parental reports of sibling
      temperament and child feeding practices and attitudes, suggesting that
      temperament plays a role in how parents feed their children.

PMID- 21740940
TI  - Mesenchymal stem cells engineered for cancer therapy.
AB  - Recent pre-clinical and clinical studies have shown that stem cell-based
      therapies hold tremendous promise for the treatment of human disease. Mesenchymal
      stem cells (MSC) are emerging as promising anti-cancer agents which have an
      enormous potential to be utilized to treat a number of different cancer types.
      MSC have inherent tumor-trophic migratory properties, which allows them to serve
      as vehicles for delivering effective, targeted therapy to isolated tumors and
      metastatic disease. MSC have been readily engineered to express anti
      proliferative, pro-apoptotic, anti-angiogenic agents that specifically target
      different cancer types. Many of these strategies have been validated in a wide
      range of studies evaluating treatment feasibility or efficacy, as well as
      establishing methods for real-time monitoring of stem cell migration in vivo for
      optimal therapy surveillance and accelerated development. This review aims to
      provide an in depth status of current MSC-based cancer therapies, as well as the
      prospects for their clinical translation.

PMID- 21740942
TI  - Doxycycline could aggravate the absence-like epileptic seizures of WAG/Rij rats
      via matrix metalloproteinase inhibition.
AB  - Matrix metalloproteinases (MMPs) are known to be activated in the brain by
      epileptic seizures and elevated MMP-9 activity has been found in a genetic model
      of generalized absence epilepsy (Wistar Albino Glaxo Rijswijk/WAG/Rij rats). In
      this study we posed the question, whether MMP inhibitory dose of doxycycline
      (20mg/kg) could affect the spike-wave-discharges (SWDs) of the WAG/Rij rat. We
      found that intraperitoneal (i.p.) administration of 20mg/kg doxycycline
      significantly increased the incidence and duration of SWDs for 4h. As doxycycline
      has both MMP inhibitory and anti-inflammatory effects we also tested a lower dose
      of doxycycline (10mg/kg, i.p.) and a selective broad-spectrum MMP inhibitor
      GM6001 (N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl]-L-tryptophane
      methylamide) intracerebroventricularly (i.c.v., 10 ng/rat). While 10mg/kg
      doxycycline significantly increased the SWD number for 1h, GM6001 significantly
      increased the SWD number during the whole 4-h recording period. Our results could
      indicate that the induction of MMPs in the epileptic brain, besides contributing
      to structural remodeling, would also be associated with such functions as
      homeostatic synaptic plasticity which might counteract epileptic seizures.

PMID- 21740943
TI  - Neuroprotective effects of quercetin, rutin and okra (Abelmoschus esculentus
      Linn.) in dexamethasone-treated mice.
AB  - The administration of dexamethasone, a synthetic glucocorticoid receptor agonist,
      causes neuronal death in the CA3 layer of the hippocampus, which has been
      associated with learning and memory impairments. This study aimed to examine the
      ability of okra (Abelmoschus esculentus Linn.) extract and its derivatives
      (quercetin and rutin) to protect neuronal function and improve learning and
      memory deficits in mice subjected to dexamethasone treatment. Learning and memory
      functions in mice were examined using the Morris water maze test. The results
      showed that the mice treated with dexamethasone had prolonged water maze
      performance latencies and shorter time spent in the target quadrant while mice
      pretreated with quercetin, rutin or okra extract prior to dexamethasone treatment
      showed shorter latencies and longer time spent in target quadrant. Morphological
      changes in pyramidal neurons were observed in the dexamethasone treated group.
      The number of CA3 hippocampal neurons was significantly lower while pretreated
      with quercetin, rutin or okra attenuated this change. Prolonged treatment with
      dexamethasone altered NMDA receptor expression in the hippocampus. Pretreatment
      with quercetin, rutin or okra extract prevented the reduction in NMDA receptor
      expression. Dentate gyrus (DG) cell proliferation was examined using the 5-bromo
      2-deoxyuridine (BrdU) immunohistochemistry technique. The number of BrdU
      immunopositive cells was significantly reduced in dexamethasone-treated mice
      compared to control mice. Pretreatment with okra extract, either quercetin or
      rutin was found to restore BrdU-immunoreactivity in the dentate gyrus. These
      findings suggest that quercetin, rutin and okra extract treatments reversed
      cognitive deficits, including impaired dentate gyrus (DG) cell proliferation, and
      protected against morphological changes in the CA3 region in dexamethasone
      treated mice. The precise mechanism of the neuroprotective effect of these plant
      extracts should be further investigated.

PMID- 21740944
TI  - Association between the activation of MCH and orexin immunorective neurons and
      REM sleep architecture during REM rebound after a three day long REM deprivation.
AB  - Rapid eye movement (REM) sleep rebound following REM deprivation using the
      platform-on-water method is characterized by increased time spent in REM sleep
      and activation of melanin-concentrating hormone (MCH) expressing neurons.
      Orexinergic neurons discharge reciprocally to MCH-ergic neurons across the sleep
      wake cycle. However, the relation between REM architecture and the aforementioned
      neuropeptides remained unclear. MCH-ergic neurons can be divided into two
      subpopulations regarding their cocaine- and amphetamine-regulated transcript
      (CART) immunoreactivity, and among them the activation of CART-immunoreactive
      subpopulation is higher during the REM rebound. However, the possible role of
      stress in this association has not been elucidated. Our aims were to analyze the
      relationship between the architecture of REM rebound and the activation of
      hypothalamic MCH-ergic and orexinergic neurons. We also intended to separate the
      effect of stress and REM deprivation on the subsequent activation of
      subpopulations of MCH-ergic neurons. In order to detect neuronal activity, we
      performed MCH/cFos and orexin/cFos double immunohistochemistry on home cage,
      sleep deprived and sleep-rebound rats using the platform-on-water method with
      small and large (stress control) platforms. Furthermore, REM architecture was
      analyzed and a triple MCH/CART/cFos immunohistochemistry was also performed on
      the rebound groups in the same animals. We found that the activity of MCH- and
      orexin-immunoreactive neurons during REM rebound was positively and negatively
      correlated with the number of REM bouts, respectively. A negative reciprocal
      correlation was also found between the activation of MCH- and orexin
      immunoreactive neurons during REM rebound. Furthermore, difference between the
      activation of CART-immunoreactive (CART-IR) and non-CART-immunoreactive MCH-ergic
      neuron subpopulations was found only after selective REM deprivation, it was
      absent in the large platform (stress control) rebound group. These results
      support the role of CART-IR subpopulation of MCH-ergic neurons and the inverse
      relationship of MCH and orexin in the regulation of REM sleep after REM sleep
      deprivation.

PMID- 21740945
TI  - Progesterone receptor isoforms differentially regulate the expression of
      tryptophan and tyrosine hydroxylase and glutamic acid decarboxylase in the rat
      hypothalamus.
AB  - Progesterone exerts a variety of actions in the brain through the interaction
      with its receptors (PR) which have two isoforms with different function and
      regulation: PR-A and PR-B. Progesterone may modulate neurotransmission by
      regulating the expression of neurotransmitters synthesizing enzymes or their
      receptors in several brain regions. The role of PR isoforms in this modulation is
      unknown. We explored the role of PR isoforms in the regulation of tryptophan
      (TPH) and tyrosine (TH) hydroxylase, and glutamic acid decarboxylase (GAD)
      expression in the hypothalamus of ovariectomized rats. Two weeks after
      ovariectomy, animals were subcutaneously injected with 5 MUg of estradiol
      benzoate (EB), and 40 h later, progesterone (P) was intracerebroventricularly
      (ICV) injected. Each animal received two ICV injections of 1 MUg/MUl (4 nmol) of
      PR-B and total PR (PR-A+PR-B) sense or antisense (As) oligonucleotides (ODNs).
      First injection was made immediately before sc EB injection, and 24h later
      animals received the second one. Twenty-four hours after P administration, rats
      were euthanized and brains removed to measure the expression of PR-A and PR-B,
      TPH, TH and GAD by Western blot. We observed that sense ODNs modified neither PR
      isoforms nor enzymes expression in the hypothalamus, whereas PR A+B antisense (PR
      A+B As) clearly decreased the expression of both PR isoforms in this region. ICV
      administration of PR-B As only decreased PR-B isoform expression with no
      significant effects on PR-A expression. A differential protein expression of TPH,
      TH and GAD was observed after PR isoforms antisense administration. PR-B As
      administration decreased the expression of TPH (65% with respect to control). In
      contrast, PR A+B As and PR-B As administration increased (51.6% and 34.4%,
      respectively) TH expression. The administration of PR A+B As and PR-B As
      diminished GAD expression (33.4% and 41.6%, respectively). Our findings indicate
      that PR isoforms play a differential role in the regulation of the content of
      TPH, TH and GAD in the rat hypothalamus.

PMID- 21740946
TI  - Transcutaneous vaccines: novel advances in technology and delivery for overcoming
      the barriers.
AB  - Transcutaneous immunization represents an attractive alternative to vaccine
      delivery via topical administration and has received wide attention due to its
      easy-to-use, needle-free and noninvasive delivery. However, the development of
      transcutaneous vaccine was kept a challenge because of the barrier function of
      stratum corneum which inhibits the transport of antigen and adjuvant. Nowadays,
      pharmaceutical methods and novel physical devices are extensively investigated to
      overcome the penetration barrier of the stratum corneum for transcutaneous
      vaccine. In this article, these pharmaceutical methods and novel devices used for
      the enhancement of transcutaneous immunization were reviewed. In addition,
      chemokines promoted the migration of Langerhans cells and the transcutaneous
      adjuvants enhancing the immune responses at certain levels are also discussed for
      the development of novel transcutaneous vaccines.

PMID- 21740947
TI  - Barriers of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness
      studies.
AB  - Barriers to participation in an HIV vaccine trial have been examined in many HIV
      vaccine preparedness studies (VPS). These barriers can be understood in terms of
      the locus of the barrier (personal vs. social) and the nature of the barrier
      (risk vs. cost). Another type of barrier is perceived misconceptions. In this
      systematic review, we categorize barriers, and compare these barriers between the
      Organization for Economic Co-operation and Development (OECD) countries and the
      non-OECD countries. In the OECD countries, we retrieved 25 studies reporting
      personal risks (PR), 9 studies reporting social risks (SR), 10 studies reporting
      personal costs (PC), and 16 studies reporting misconceptions. In the non-OECD
      countries, we retrieved 27 studies reporting PR, 19 studies reporting SR, 18
      studies reporting PC, 1 study reporting social costs (SC), and 13 studies
      reporting misconceptions. Important PR were "adverse effects" and "vaccine
      induced seropositivity", "distrust of institutions", and "temptation to have
      unsafe sex" in men who have sex with men (MSM). "Discrimination" was a common SR.
      "Time commitment" was an important PC, and "family commitments" were a SC in one
      non-OECD country. "HIV infection from the vaccine" was a common misconception.
      Both the OECD and the non-OECD countries have similar barriers, and people's
      decisions to participate in a clinical trial involve multiple barriers. However,
      these barriers apply to hypothetical HIV vaccine trials, and barriers for actual
      vaccine trials need further assessment.

PMID- 21740948
TI  - Venlafaxine in somatopsychic and autopsychic depersonalization.

PMID- 21740949
TI  - Assessing the effects of gamma irradiation and storage time in energetic value
      and in major individual nutrients of chestnuts.
AB  - Chestnut (Castanea sativa Miller) is an important food resource all over the
      world. In the present study, it is intended to evaluate if the application of
      gamma irradiation doses <= 3 kGy maintain chestnuts chemical and nutritional
      profiles unaffected. Furthermore, possible interactions among irradiation dose
      and storage time were accessed using linear discriminate analysis (LDA). The
      nutritional composition was evaluated through determination of proteins, fat,
      ash, carbohydrates and energetic value. The chemical composition was focused in
      the main nutrients found in chestnuts: sugars - sucrose, fatty acids - palmitic,
      oleic, linoleic and linolenic acids, tocopherols - gamma-tocopherol. The obtained
      results seem to indicate that the irradiation treatment did not affect the
      nutritional and chemical quality of chestnut fruits. Otherwise, storage time
      exerted more evident influence in those parameters. The application of gamma
      irradiation emerges as a promising technology for chestnuts chemical quality, but
      food safety issues have to be evaluated in order to recommend its application as
      a useful conservation alternative.

PMID- 21740950
TI  - Measurement of glycidol hemoglobin adducts in humans who ingest edible oil
      containing small amounts of glycidol fatty acid esters.
AB  - Hemoglobin (Hb) adducts are frequently used to address and/or monitor exposure to
      reactive chemicals. Glycidol (G), a known animal carcinogen, has been reported to
      form Hb adducts. Here, we measure G adduct levels in humans who daily ingest DAG
      oil, an edible oil consisting mainly of diacylglycerol. Since DAG oil contains a
      small amount of glycidol fatty acid esters (GEs), possible exposure to G released
      from GEs has been raised as a possible concern. For measurement of Hb adducts, we
      employed the N-alkyl Edman method reported by Landin et al. (1996) using gas
      chromatography-tandem mass spectrometry with minor modifications to detect G-Hb
      adducts as N-(2,3-dihydroxy-propyl)valine (diHOPrVal). Blood samples were
      collected from 7 DAG oil users and 6 non-users, and then G-Hb adduct levels were
      measured. G-Hb adducts were detected in all samples. The average level of
      diHOPrVal was 3.5+/-1.9pmol/g globin in the DAG oil users and 7.1+/-3.1pmol/g
      globin in the non-users. We conclude that there is no increased exposure to G in
      individuals who daily ingest DAG oil.

PMID- 21740951
TI  - Protective effect of Diyarbakir watermelon juice on carbon tetrachloride-induced
      toxicity in rats.
AB  - The present study was designed to evaluate the effect of Diyarbakir watermelon
      (Citrullus lanatus cv. Surme) juice on lipid peroxidation states in rat liver,
      kidney and brain. In vivo administration of carbon tetrachloride (CCl(4)) once a
      week for 28 days caused a significant elevation of serum markers of liver damage,
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin
      (TB) and decrease in albumin when compared to the control group. However,
      administration of carbon tetrachloride along with watermelon juice or
      ursodeoxycolic acid (UDCA) significantly reduces these changes. Increased lipid
      peroxide (LPO) level was observed in the liver, kidney and brain tissues after
      CCl(4) administration. However, watermelon juice and UDCA treatment prevented the
      increase in LPO. The results indicated that watermelon juice protects the liver,
      kidney and brain tissues from experimental CCl(4) toxicity in rats and that the
      protective effect of watermelon juice may be due to its antioxidant activity and
      inhibition of lipid peroxide formation. In conclusion, present study reveals
      biological evidence that supports the use of watermelon juice in the treatment of
      chemical-induced hepatotoxicity.

PMID- 21740952
TI  - Leptin resistance develops spontaneously in mice during adult life in a tissue
      specific manner. Consequences for hepatic steatosis.
AB  - Leptin is an adipocyte-derived hormone which stimulates beta-oxidation in
      peripheral tissues and prevents steatosis. Because leptin production naturally
      increases during adult life, we have hypothesized that leptin receptors might
      undergo a physiological and gradual desensitization during ageing. Therefore we
      have characterized in three- five- and ten-month old mice i) the weight of
      different white adipose pads, heart and liver, ii) lipid content in these
      tissues/organs, and iii) responsiveness to acute leptin, measured in terms of
      phosphorylation of signal transducer and activator of transcription 3 (STAT3) and
      protein kinase B (Akt). In this study we have detected that leptin-mediated STAT3
      phosphorylation appears to be preserved in cardiac tissue even in 10-month old
      animals but not in adipose tissue and liver of five- and ten-month old mice,
      respectively. Nevertheless, leptin increased pAkt content in the liver of these
      mice. In a parallel study we have analyzed the functionality of leptin signalling
      pathways in 10-month old obese mice and we have observed that the STAT3 pathway
      appears to be only operative in the heart whereas the Akt pathway remains
      functional both in heart and liver. Nevertheless, hepatic lipids increased almost
      300% compared to age-matched lean controls. Our data demonstrate that during
      adult life there is a lost of leptin receptor functionality which is tissue
      dependent and mainly affects the STAT3 pathway. Otherwise we demonstrate that the
      antisteatotic effect of leptin is independent of the Akt signalling pathway.

PMID- 21740953
TI  - Lipid hydration and mobility: an interplay between fluorescence solvent
      relaxation experiments and molecular dynamics simulations.
AB  - Fluorescence solvent relaxation experiments are based on the characterization of
      time-dependent shifts in the fluorescence emission of a chromophore, yielding
      polarity and viscosity information about the chromophore's immediate environment.
      A chromophore applied to a phospholipid bilayer at a well-defined location (with
      respect to the z-axis of the bilayer) allows monitoring of the hydration and
      mobility of the probed segment of the lipid molecules. Specifically, time
      resolved fluorescence experiments, fluorescence quenching data and molecular
      dynamic (MD) simulations show that 6-lauroyl-2-dimethylaminonaphthalene (Laurdan)
      probes the hydration and mobility of the sn-1 acyl groups in a
      phosphatidylcholine bilayer. The time-dependent fluorescence shift (TDFS) of
      Laurdan provides information on headgroup compression and expansion induced by
      the addition of different amounts of cationic lipids to phosphatidylcholine
      bilayers. Those changes were predicted by previous MD simulations. Addition of
      truncated oxidized phospholipids leads to increased mobility and hydration at the
      sn-1 acyl level. This experimental finding can be explained by MD simulations,
      which indicate that the truncated chains of the oxidized lipid molecules are
      looping back into aqueous phase, hence creating voids below the glycerol level.
      Fluorescence solvent relaxation experiments are also useful in understanding salt
      effects on the structure and dynamics of lipid bilayers. For example, such
      experiments demonstrate that large anions increase hydration and mobility at the
      sn-1 acyl level of phosphatidylcholine bilayers, an observation which could not
      be explained by standard MD simulations. If polarizability is introduced into the
      applied force field, however, MD simulations show that big soft polarizable
      anions are able to interact with the hydrophilic/hydrophobic interface of the
      lipid bilayer, penetrating to the level probed by Laurdan, and that they expand
      and destabilize the bilayer making it more hydrated and mobile.

PMID- 21740954
TI  - Ribozymes: Flexible molecular devices at work.
AB  - The discovery of ribozymes, RNAs with catalytic activity, revealed the
      extraordinary characteristic of this molecule, and corroborated the idea that RNA
      was the first informative polymer. The "RNA world" hypothesis asserts that the
      DNA/RNA/PROTEIN world arose from an earlier RNA world in which were present only
      RNA molecules able to perform both of the two functions performed separately by
      DNA and proteins in the present-day cells: the ability to transfer genetic
      information and to carry out catalytic activity. The catalytic properties of
      ribozymes are exclusively due to the capacity of RNA molecules to assume
      particular structures. Moreover, the structural versatility of RNA can allow to a
      single RNA sequence to fold in more than one structure, able to perform more than
      one function. In the first part of this work we will discuss the RNA plasticity,
      focusing on "bifunctional" ribozymes isolated by in vitro selection experiments,
      and on the consequences of this plasticity in the prospective of the emergence of
      new specific functions. The possibility that one sequence could have more than
      one structure/function, greatly increase the evolutionary potential of RNA, and
      the capacity of RNA to switch from a structure/function to another is probably
      one of the reasons of the evolutionary success also in modern-day cells.
      Naturally occurring ribozymes discovered in contemporary cells, demonstrate the
      crucial role that ribozymes still have in the modern protein world. In the second
      part of this paper we will discuss the capacity of natural ribozymes to modulate
      gene expression making use of their exclusive catalytic properties. Moreover, we
      will consider the possibility of their ancient origin.

PMID- 21740955
TI  - Mechanism of stereoselective interaction between butyrylcholinesterase and
      ethopropazine enantiomers.
AB  - Stereoselectivity of reversible inhibition of butyrylcholinesterase (BChE; EC
      3.1.1.8) by optically pure ethopropazine [10-(2-diethylaminopropyl)phenothiazine
      hydrochloride] enantiomers and racemate was studied with acetylthiocholine (0.002
      250 mM) as substrate. Molecular modelling resulted in the reaction between BChE
      and ethopropazine starting with the binding of ethopropazine to the enzyme
      peripheral anionic site. In the next step ethopropazine 'slides down' the enzyme
      gorge, resulting in interaction of the three rings of ethopropazine through pi-pi
      interactions with W82 in BChE. Inhibition mechanism was interpreted according to
      three kinetic models: A, B and C. The models differ in the type and number of
      enzyme-substrate, enzyme-inhibitor and enzyme-substrate-inhibitor complexes,
      i.e., presence of the Michaelis complex and/or acetylated BChE. Although, all
      three models reproduced well the BChE activity in absence of ethopropazine, model
      A was poor in describing inhibition with ethopropazine, while models B and C were
      better, especially for substrate concentrations above 0.2 mM. However model C was
      singled out because it approaches fulfilment of the one step-one event criteria,
      and confirms the inhibition mechanism derived from molecular modelling. Model C
      resulted in dissociation constants for the complex between BChE and
      ethopropazine: 61, 140 and 88 nM for R-enantiomer, S-enantiomer and racemate,
      respectively. The respective dissociation constants for the complexes between
      acetylated BChE and ethopropazine were 268, 730 and 365 nM. Butyrylcholinesterase
      had higher affinity for R-ethopropazine.

PMID- 21740956
TI  - Age related macular degeneration and drusen: neuroinflammation in the retina.
AB  - Inflammation protects from dangerous stimuli, restoring normal tissue
      homeostasis. Inflammatory response in the nervous system ("neuroinflammation")
      has distinct features, which are shared in several diseases. The retina is an
      immune-privileged site, and the tight balance of immune reaction can be disrupted
      and lead to age-related macular disease (AMD) and to its peculiar sign, the
      druse. Excessive activation of inflammatory and immunological cascade with
      subsequent induction of damage, persistent activation of resident immune cells,
      accumulation of byproducts that exceeds the normal capacity of clearance giving
      origin to a chronic local inflammation, alterations in the activation of the
      complement system, infiltration of macrophages, T-lymphocytes and mast-cells from
      the bloodstream, participate in the mechanisms which originate the drusen. In
      addition, aging of the retina and AMD involve also para-inflammation, by which
      immune cells react to persistent stressful stimuli generating low-grade
      inflammation, aimed at restoring function and maintaining tissue homeostasis by
      varying the set point in relation to the new altered conditions. This mechanism
      is also seen in the normal aging retina, but, in the presence of noxious stimuli
      as in AMD, it can become chronic and have an adverse outcome. Finally, autophagy
      may provide new insights to understand AMD pathology, due to its contribution in
      the removal of defective proteins. Therefore, the AMD retina can represent a
      valuable model to study neuroinflammation, its mechanisms and therapy in a
      restricted and controllable environment. Targeting these pathways could represent
      a new way to treat and prevent both exudative and dry forms of AMD.

PMID- 21740957
TI  - Polyglutamine diseases: the special case of ataxin-3 and Machado-Joseph disease.
AB  - Polyglutamine (polyQ) diseases are a group of nine neurodegenerative disorders
      caused by an unstable CAG expansion in the codifying region of their respective
      associated genes. However, each polyQ disease displays a different symptomatic
      and pathoanatomic profile and the proteins involved share no homology outside the
      polyQ tract. This suggests that the other regions of the proteins and the
      cellular functions they mediate are important in defining disease progression and
      specificity. Machado-Joseph disease (MJD), the most common form of
      spinocerebellar ataxia worldwide, is a progressive and ultimately fatal
      neurodegenerative disorder caused by polyQ expansion in ataxin-3 (atx3), a
      conserved and ubiquitous protein known to bind polyubiquitin chains and to
      function as a deubiquitinating enzyme. Atx3 has been linked to protein
      homeostasis maintenance, transcription, cytoskeleton regulation and myogenesis,
      but its precise biologic function remains a mystery, limiting the understanding
      of the mechanisms by which the mutated protein leads to the selective neuronal
      death profile observed in MJD patients. A number of recent evidence support the
      idea that the toxic entities behind neuronal demise may be either the
      dysfunctional expanded atx3 or the soluble amyloid-like oligomers formed by self
      assembly of the aggregation-prone mutated protein. Expanded atx3 pathogenicity is
      likely the result of a series of events implicating both atx3 dysfunction and
      aggregation, possibly involving both full-length atx3 and polyQ-containing
      fragments that may act as seeds for protein aggregation. A deeper understanding
      of polyQ protein biology, the way the expansion alters their features, and the
      consequences of these changes for cell functioning and survival are sure to be of
      critical importance for developing future treatment of polyQ diseases.

PMID- 21740958
TI  - The role of estrogen-metabolizing enzymes and estrogen receptors in human
      epidermis.
AB  - Local estrogen metabolism and its sensitivities in the skin have been also
      suggested to contribute to skin homeostasis in addition to age- and/or gender
      dependent circulating estrogen, even though their local mechanisms have been
      largely unknown. To characterize their potential correlations, age- and gender
      dependencies were evaluated focusing on 5 pivotal estrogen-metabolizing enzymes
      including aromatase, estrogen sulfotransferase, steroid sulfatase, and 17beta
      hydroxysteroid dehydrogenases and estrogen receptors (ERalpha and ERbeta) using
      immunohistochemistry of 100 human skin specimens. When their epidermal expression
      levels were compared among 7 age groups, ranging from the teens to the seventies,
      the highest expression in the teens group and the lowest expression in the
      seventies group were found in the expression of aromatase and ERbeta,
      respectively, while no significant differences between the male and the female
      groups were found in the immunoreactivities of our interested proteins. Our
      results suggest that age-related differences in aromatase and ERbeta expressions
      impact epidermal homeostasis.

PMID- 21740959
TI  - Observation of tool use and modification for apparent hygiene purposes in a
      mandrill.
AB  - Tool making or modification to produce a tool of apparent improved functionality
      has rarely been reported in monkeys, especially when tools are used outside the
      context of food acquisition. We report on an observation of selection,
      modification and use of splinters for hygiene purposes in a male mandrill. The
      zoo-housed animal was video-recorded breaking splinters in sequence to use them
      underneath his toenails. This record brings forward new evidence that the ability
      to use and modify tools is not limited to apes and some New World monkeys but is
      also apparent in Old Word monkeys.

PMID- 21740960
TI  - Edetate calcium disodium nanoparticle dry powder inhalation: a novel approach
      against heavy metal decorporation.
AB  - Objective was to develop and characterize nano-edetate calcium disodium (Ca
      Na(2)EDTA) dry powder inhaler (DPI), and assess its in vitro and in vivo
      deposition using pharmacoscintigraphy techniques. Factors influencing
      nanoparticle formation including concentration of drug, polymer solution and
      stirring rate were determined. Optimized formulation was characterized with the
      help of SEM, TEM and Malvern Zetasizer studies. Any change in physical
      characteristics after nanosizing was determined by FT-IR, XRD and DSC studies.
      Anderson cascade impaction showed that nano Ca-Na(2)EDTA exhibited significantly
      higher respirable fraction of 67.35+/-2.27% and 66.40+/-2.87% by scintigraphic
      and spectroscopic analysis respectively, as compared to 10.08+/-1.17% and 9.36+/
      1.02% respectively for micronized form. Ventilation lung scintigraphy done in 12
      volunteers showed significant increase in drug delivery till alveolar region with
      nano Ca-Na(2)EDTA. The developed formulation may have a role in neutralizing
      heavy metal toxicity through inhalation route, including radio-metal
      contamination.

PMID- 21740961
TI  - Extracts from a traditional Chinese herbal remedy (Zhuyun recipe) improve
      endometrial receptivity in mice with embryonic implantation dysfunction and
      ovulation stimulation.
AB  - OBJECTIVE: Although ovarian stimulation has an important role in assisted
      reproductive technologies (ART), it may also have detrimental effects on
      endometrial receptivity. Traditional Chinese herbal remedy, as a kind of
      traditional treatments, has been widely and increasingly applied in clinic. In
      this article, the impact of traditional Chinese medicines (TCM) on embryonic
      implantation, pregnant rate and underlying mechanisms will be investigated.
      METHODS: One hundred and sixty-three female pregnant kunming mice were randomly
      divided into 6 groups, including A, control group; B, ovulation stimulation (OS)
      group; C, OS+TCM group; D, embryo implantation dysfunction (EID) group; E,
      EID+TCM group; F, TCM only group. Uterus samples were collected at gestation Day
      4 and were detected with immunohistochemistry and Real Time-PCR analyses. Uterine
      horns were excised to determine the number of pregnant mice and implantation
      sites on the Day 8 postcoitum. RESULTS: OS group and EID group showed a
      significant decrease in pregnant rate and the expression of both the endometrial
      leukaemia inhibitory factor (LIF) and integrin beta3 subunit during the
      implantation window. OS+TCM group and EID+TCM group showed a higher pregnant rate
      and endometrial LIF and integrin beta3 subunit expression compared to OS group
      and EID group. The number of implanted embryo in EID group was lower than in
      control group, but higher in EID+TCM group than in EID group. No significant
      difference was found in the measured indices between the TCM only group and
      control group. CONCLUSIONS: OS model and EID model may have a negative influence
      on endometrial receptivity and embryonic implantation in mice. Conversely, TCM
      appears to reverse the expression of endometrial LIF and integrin beta3 subunit,
      improves the uterine receptivity in mice and increases pregnant rate and
      embryonic implantation. It provides a new insight into the clinic infertility's
      treatment.

PMID- 21740962
TI  - The protein interaction network mediated by human SH3 domains.
AB  - Families of conserved protein domains, specialized in mediating interactions with
      short linear peptide motifs, are responsible for the formation of a variety of
      dynamic complexes in the cell. An important subclass of these motifs are
      characterized by a high proline content and play a pivotal role in biological
      processes requiring the coordinated assembly of multi-protein complexes. This is
      achieved via interaction of proteins containing modules such as Src Homology-3
      (SH3) or WW domains and specific proline rich patterns. Here we make available
      via a publicly accessible database a synopsis of our current understanding of the
      interaction landscape of the human SH3 protein family. This is achieved by
      integrating an information extraction strategy with a new experimental approach.
      In a first approach we have used a text mining strategy to capture a large number
      of manuscripts reporting interactions between SH3 domains and target peptides.
      Relevant information was annotated in the MINT database. In a second experimental
      approach we have used a variant of the WISE (Whole Interactome Scanning
      Experiment) strategy to probe a large number of naturally occurring and
      chemically-synthesized peptides arrayed at high density on a glass surface. By
      this method we have tested 60 human SH3 domains for their ability to bind a
      collection of 9192 poly-proline containing peptides immobilized on a glass chip.
      To evaluate the quality of the resulting interaction dataset, we retested some of
      the interactions on a smaller scale and performed a series of pull down
      experiments on native proteins. Peptide chips, pull down assays, SPOT synthesis
      and phage display experiments have allowed us to further characterize the
      specificity and promiscuity of proline-rich binding domains and to map their
      interaction network. Both the information captured from the literature and the
      interactions inferred from the peptide chip experiments were collected and stored
      in the PepspotDB (http://mint.bio.uniroma2.it/PepspotDB/).

PMID- 21740963
TI  - Stem cell-biomaterial interactions for regenerative medicine.
AB  - The synergism of stem cell biology and biomaterial technology promises to have a
      profound impact on stem-cell-based clinical applications for tissue regeneration.
      Biomaterials development is rapidly advancing to display properties that, in a
      precise and physiological fashion, could drive stem-cell fate both in vitro and
      in vivo. Thus, the design of novel materials is trying to recapitulate the
      molecular events involved in the production, clearance and interaction of
      molecules within tissue in pathologic conditions and regeneration of
      tissue/organs. In this review we will report on the challenges behind translating
      stem cell biology and biomaterial innovations into novel clinical therapeutic
      applications for tissue and organ replacements (graphical abstract).

PMID- 21740964
TI  - Heteromerization of angiotensin receptors changes trafficking and arrestin
      recruitment profiles.
AB  - The cardiovascular hormone angiotensin II (AngII) exerts its actions via two G
      protein-coupled receptor (GPCR) subtypes, AT(1) and AT(2), which often display
      antagonistic functions. Methodological constraints have so far precluded detailed
      analyses of the ligand-dependency, cellular localization, and functional
      relevance of AngII receptor interactions in live cells. In this study, we utilize
      a protein-fragment complementation assay (PCA) and GPCR-Heteromer Identification
      Technology (GPCR-HIT) to provide the first detailed investigation of the ligand
      dependency and cellular localization of AngII receptor interactions in human
      embryonic kidney 293 cells. Fluorescent-tagged receptor constructs for PCA and
      GPCR-HIT displayed normal affinity and selectivity for AngII (AT(1): IC(50)=1.0
      1.6nM; AT(2): IC(50)=2.0-3.0nM). Well-characterized angiotensin receptor
      interactions were used as positive and negative controls to demonstrate the
      sensitivity and specificity of these fluorescence-based assays. We report that
      AT(1)-AT(2) receptor heteromers form constitutively, are localized to the plasma
      membrane and perinuclear compartments, and do not internalize following AngII
      stimulation despite arrestin being recruited specifically to the heteromer. Our
      findings using novel fluorescence-based technologies reveal a previously
      unrecognized mechanism of angiotensin receptor cross-talk involving cross
      inhibition of AT(1) receptor internalization through heteromerization with the
      AT(2) receptor subtype.

PMID- 21740965
TI  - Phospholipase C-eta2 is activated by elevated intracellular Ca(2+) levels.
AB  - Phospholipase C-eta2 (PLCeta2) is a novel enzyme whose activity in a cellular
      context is largely uncharacterised. In this study the activity of PLCeta2 was
      examined via [(3)H]inositol phosphate release in COS7 cells expressing the
      enzyme. PLCeta2 activity increased approximately 5-fold in response to monensin,
      a Na(+)/H(+) antiporter. This was significantly inhibited by CGP-37157 which
      implies that the effect of monensin was due, at least in part, to mitochondrial
      Na(+)/Ca(2+)-exchange. Direct activation of PLCeta2 by <1MUM Ca(2+) was confirmed
      in permeabilised transfected cells. The roles of the PH and C2 domains in
      controlling PLCeta2 activity via membrane association were also investigated. A
      PH domain-lacking mutant exhibited no detectable activity in response to monensin
      or Ca(2+) due to an inability to associate with the cell membrane. Within the C2
      domain, mutation of D920 to alanine at the predicted Ca(2+)-binding site
      dramatically reduced enzyme activity highlighting an important regulatory role
      for this domain. Mutation of D861 to asparagine also influenced activity, most
      likely due to altered lipid selectivity. Of the C2 mutations investigated, none
      altered sensitivity to Ca(2+). This suggests that the C2 domain is not
      responsible for Ca(2+) activation. Collectively, this work highlights an
      important new component of the Ca(2+) signalling toolkit and given its
      sensitivity to Ca(2+), this enzyme is likely to facilitate the amplification of
      intracellular Ca(2+) transients and/or crosstalk between Ca(2+)-storing
      compartments in vivo.

PMID- 21740966
TI  - The specificities of small molecule inhibitors of the TGFbeta and BMP pathways.
AB  - Small molecule inhibitors of type 1 receptor serine threonine kinases (ALKs1-7),
      the mediators of TGFbeta and BMP signals, have been employed extensively to
      assess their physiological roles in cells and organisms. While all of these
      inhibitors have been reported as "selective" inhibitors of specific ALKs,
      extensive specificity tests against a wide array of protein kinases have not been
      performed. In this study, we examine the specificities and potencies of the most
      frequently used small molecule inhibitors of the TGFbeta pathway (SB-431542, SB
      505124, LY-364947 and A-83-01) and the BMP pathway (Dorsomorphin and LDN-193189)
      against a panel of up to 123 protein kinases covering a broad spectrum of the
      human kinome. We demonstrate that the inhibitors of the TGFbeta pathway are
      relatively more selective than the inhibitors of the BMP pathway. Based on our
      specificity and potency profile and published data, we recommend SB-505124 as the
      most suitable molecule for use as an inhibitor of ALKs 4, 5 and 7 and the TGFbeta
      pathway. We do not recommend Dorsomorphin, also called Compound C, for use as an
      inhibitor of the BMP pathway. Although LDN-193189, a Dorsomorphin derivative, is
      a very potent inhibitor of ALK2/3 and the BMP-pathway, we found that it potently
      inhibited a number of other protein kinases at concentrations sufficient to
      inhibit ALK2/3 and its use as a selective BMP-pathway inhibitor has to be
      considered cautiously. Our observations have highlighted the need for caution
      when using these small molecule inhibitors to assess the physiological roles of
      BMP and TGFbeta pathways.

PMID- 21740968
TI  - An autophagy gene, TrATG5, affects conidiospore differentiation in Trichoderma
      reesei.
AB  - Autophagy is a highly conserved process in lower to higher eukaryotic organisms,
      and occurs in many types of cells as tissues are remodeled during development. In
      this study, we investigated the functional role of the Trichoderma reesei TrATG5
      gene, which encodes an essential protein required for autophagy. TrATG5 is
      conserved in structure and function in the filamentous fungi and might clearly
      rescue the pathogenicity function of MgATG5 in Magnaporthe oryzae. Target gene
      disruption was used to study the functions of TrATG5. It was found that the
      autophagic process was blocked in the TrATG5 deletion mutant. The mutant was
      sensitive to nutrient starvation, with abnormal conidiophores and reduced
      production of conidia. This new evidence might help to elucidate the molecular
      machinery of autophagy in filamentous fungi.

PMID- 21740969
TI  - Mechanism-based pharmacokinetic-pharmacodynamic modeling of the estrogen-like
      effect of ginsenoside Rb1 on neural 5-HT in ovariectomized mice.
AB  - We sought to develop a mechanism-based pharmacokinetic-pharmacodynamic (PK-PD)
      model to characterize the effects of ginsenoside Rb1 (Rb1) and estradiol (E(2))
      on neural 5-hydroxytryptamine (5-HT) concentration in ovariectomized mice. PK
      data of Rb1 and E(2) were obtained in plasma and brain. Brain levels of 5-HT,
      tryptophan (TRP), 5-hydroxytryptophan (5-HTP), and 5-hydroxyindoleacetic acid (5
      HIAA) were determined after a single intravenous injection of Rb1 (20mg/kg) and
      E(2) (0.2mg/kg) in ovariectomized mice. The activities of tryptophan hydroxylase
      (TPH), aromatic amino acid decarboxylase (AAAD), and monoamine oxidase (MAO) were
      also evaluated. Rb1 and E(2) elevated neural 5-HT levels via TPH activation and
      MAO inhibition, respectively. Effects were well described by the mechanism-based
      PK-PD model. The net effect of increased 5-HT induced by MAO inhibition is
      greater than TPH activation. The increased brain levels of 5-HT induced by Rb1
      and E(2) were well described by the present PK-PD model, suggesting the use and
      further development of this mechanism-based model for the effects of ginsenoside
      on brain 5-HT levels.

PMID- 21740970
TI  - Azithromycin decreases MMP-9 expression in the airways of lung transplant
      recipients.
AB  - The neomacrolide antibiotic azithromycin is known to have an anti-inflammatory
      effect and is increasingly being used in the treatment of chronic inflammatory
      pulmonary diseases. We investigated whether azithromycin influenced matrix
      remodeling. Matrix metalloproteinase (MMP)-9 protein levels were measured by
      ELISA in bronchoalveolar lavaga fluid in 10 stable patients and in 10 lung
      transplant patients suffering from nCLAD/NRAD. MMP-9 was measured via ELISA
      before and after 3 to 6 months of azithromycin therapy. We further elaborated on
      the role of MMP-9 by performing gelatin-zymography and gelatinolytic activity
      assays. Differential and total cell counts on BAL were performed in all cases.
      The nCLAD/NRAD patients showed higher airway neutrophilia (p<0.0001), ELISA MMP-9
      (p<0.0001), zymography proMMP-9 (p<0.0001), activated MMP-9 (p=0.0003) and
      gelatinolytic activity (p=0.0002) compared to the control group. Airway
      neutrophilia in the nCLAD/NRAD group significantly decreased after 3-6 months of
      treatment with azithromycin (p=0.0020). This was associated with a decrease in
      ELISA MMP-9 levels (p=0.0059), in activated MMP-9 shown on zymography (p=0.016)
      and in gelatinolytic activity (p=0.031). Remarkably, proMMP-9 levels were not
      altered by azithromycin. Although azithromycin significantly reduced ELISA MMP-9
      levels and gelatinolytic activity in transplant patients, these levels remained
      higher compared to control patients (p=0.0011 and p=0.043). Neutrophil counts,
      activated MMP-9 and gelatinolytic activity levels in nCLAD/NRAD decreased after
      azithromycin treatment, but some remained elevated compared to control patients.
      This illustrates that treatment with azithromycin did not completely restore
      chronic inflammation in the airways and suggested that preventive therapy may
      yield added value to curative therapy.

PMID- 21740967
TI  - The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2,
      Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).
AB  - Phospholipase D (PLD) catalyzes the conversion of the membrane phospholipid
      phosphatidylcholine to choline and phosphatidic acid (PA). PLD's mission in the
      cell is two-fold: phospholipid turnover with maintenance of the structural
      integrity of cellular/intracellular membranes and cell signaling through PA and
      its metabolites. Precisely, through its product of the reaction, PA, PLD has been
      implicated in a variety of physiological cellular functions, such as
      intracellular protein trafficking, cytoskeletal dynamics, chemotaxis of
      leukocytes and cell proliferation. The catalytic (HKD) and regulatory (PH and PX)
      domains were studied in detail in the PLD1 isoform, but PLD2 was traditionally
      studied in lesser detail and much less was known about its regulation. Our
      laboratory has been focusing on the study of PLD2 regulation in mammalian cells.
      Over the past few years, we have reported, in regards to the catalytic action of
      PLD, that PA is a chemoattractant agent that binds to and signals inside the cell
      through the ribosomal S6 kinases (S6K). Regarding the regulatory domains of PLD2,
      we have reported the discovery of the PLD2 interaction with Grb2 via Y169 in the
      PX domain, and further association to Sos, which results in an increase of de
      novo DNA synthesis and an interaction (also with Grb2) via the adjacent residue
      Y179, leading to the regulation of cell ruffling, chemotaxis and phagocytosis of
      leukocytes. We also present the complex regulation by tyrosine phosphorylation by
      epidermal growth factor receptor (EGF-R), Janus Kinase 3 (JAK3) and Src and the
      role of phosphatases. Recently, there is evidence supporting a new level of
      regulation of PLD2 at the PH domain, by the discovery of CRIB domains and a Rac2
      PLD2 interaction that leads to a dual (positive and negative) effect on its
      enzymatic activity. Lastly, we review the surprising finding of PLD2 acting as a
      GEF. A phospholipase such as PLD that exists already in the cell membrane that
      acts directly on Rac allows a quick response of the cell without intermediary
      signaling molecules. This provides only the latest level of PLD2 regulation in a
      field that promises newer and exciting advances in the next few years.

PMID- 21740971
TI  - Reaching LDL-c targets in high-risk patients requires high-efficacy cholesterol
      lowering drugs in more than 50% of cases. The results of the CHECK study.
AB  - We estimated the need to use low-efficacy statins or high-efficacy statins or
      drug combinations to bring high- or very-high cardiovascular risk subjects to
      their LDL-c target, in a sample representative of the Italian adult population
      and according to the principles of reimbursement of hypercholesterolemic drugs
      currently used in Italy. The results allow us concluding that among high or very
      high cardiovascular risk patients about three patients out of five should be
      prescribed high-efficacy statins or drug combinations. The other two
      prescriptions might take into account lower-efficacy statins. If we also compute
      the values of HDL-c in these subjects--the large majority of which stands below
      the optimal values as suggested by International guidelines--we bring forward the
      need either to select specific statins able to increase the levels of these
      protective lipoproteins or to consider combination therapies of statins with
      fibrates or nicotinic acid. Our data might conceivably be applied to other low
      cardiovascular risk countries and should be taken into account when defining the
      proportion of drugs with different efficacy and cost in the everyday clinical
      practice.

PMID- 21740972
TI  - KV7 channels regulate muscle tone and nonadrenergic noncholinergic relaxation of
      the rat gastric fundus.
AB  - Voltage-dependent type 7 K+ (KV7) channels play important physiological roles in
      neurons and muscle cells. The aims of the present study were to investigate the
      motor effects of KV7 channel modulators in the rat gastric fundus and the
      expression of KV7 channels in this tissue. Muscle tone and electrical field
      stimulation (EFS)-evoked relaxations of precontracted longitudinal muscle strips
      of the rat gastric fundus were investigated under nonadrenergic noncholinergic
      conditions by organ bath studies. Gene expression was studied by real-time PCR
      and tissue localization of channels was investigated by immunohistochemistry. The
      KV7 channel blocker XE-991 induced concentration-dependent contractions, with
      mean pD2 and Emax of 5.4 and 48% of the maximal U46619-induced contraction,
      respectively. The KV7 channel activators retigabine and flupirtine concentration
      dependently relaxed U46619-precontracted strips, with pD2s of 4.7 and 4.4 and
      Emax of 93% and 91% of the maximal relaxation induced by papaverine,
      respectively. XE-991 concentration-dependently inhibited retigabine-induced
      relaxation with a pIC50 of 6.2. XE-991 and DMP-543, another KV7 channel blocker,
      increased by 13-25% or reduced by 11-21% the relaxations evoked by low- or high
      frequency EFS, respectively. XE-991 also reduced the relaxation induced by
      vasoactive intestinal polypeptide (VIP) by 33% of controls. Transcripts encoded
      by all KV7 genes were detected in the fundus, with 7.4 and 7.5 showing the
      highest expression levels. KV7.4 and 7.5 channels were visualized by confocal
      immunofluorescence in both circular and longitudinal muscle layers. In
      conclusion, in the rat proximal stomach, KV7 channels appear to contribute to the
      resting muscle tone and to VIP- and high-frequency EFS-induced relaxation. KV7
      channel activators could be useful relaxant agents of the gastric smooth muscle.

PMID- 21740973
TI  - Sphingosine 1-phosphate receptor modulator fingolimod (FTY720) does not promote
      remyelination in vivo.
AB  - The sphingosine 1-phosphate (S1P) receptor modulators have emerged as a new
      therapeutic opportunity paradigm for the treatment of immune-mediated
      demyelinating diseases such as multiple sclerosis (MS). The S1P analog fingolimod
      (FTY720) has been shown to alleviate disease burden in immune-mediated animal
      models of MS, and has been approved for treatment in clinical trials in patients
      with MS in the United States. While the immunological effects of FTY720 are well
      established, there is controversy in the literature regarding the contribution of
      FTY720 on myelin repair. Here, we directly assessed the impact of FTY720 on
      myelin repair in cuprizone and lysolecithin (LPC) demyelination models that have
      a minimal immunological component. FTY720 failed to promote remyelination in
      either animal model. These studies suggest that while FTY720 may be effective at
      modulating the immunological attack in MS, it may benefit from an add-on therapy
      to enhance the myelin repair required for long-term functional restoration in MS.

PMID- 21740974
TI  - Differential immune responses of the green neon shrimp (Neocaridina denticulate)
      to dipropyl phthalate.
AB  - This study set out to understand the sublethal effect of xenobiotic phthalate
      esters (PAEs) on the relationship between the susceptibility of shrimp to
      bacterial infection and the immune response of the shrimp. Neocaridina
      denticulate were exposed to different concentrations of the PAE dipropyl
      phthalate (DPrP), and mortality and six immune parameters were measured on days
      1, 3, 5, and 10 after exposure. On days 1 and 3 after exposure, shrimp exposed to
      0, 1, 5, 10, and 50 mg/L of DPrP and challenged with Aeromonas veronii
      experienced 14% and 16%, 16% and 16%, 18% and 18%, 34% and 24%, and 38% and 26%
      mortality, respectively. On day 1, five immune parameters (acid phosphatase, AcP;
      beta-glucuronidase, beta-Glu; phenoloxidase, PO; superoxide dismutase, SOD; and
      haemocyanin mRNA) were significantly altered in the all of the groups treated
      with DPrP compared to the untreated shrimp and were elevated in the 10 mg/L- and
      50 mg/L-treated groups. Beta-Glu activity and haemocyanin mRNA levels were
      significantly increased in a dose-dependent manner. These results suggest that
      the increased susceptibility of N. denticulate exposed to DPrP is short-term and
      may be related to the increased expression of DPrP-induced immune mediators.

PMID- 21740975
TI  - Activation of cannabinoid CB1 receptors in the central amygdala impairs
      inhibitory avoidance memory consolidation via NMDA receptors.
AB  - In the present study, we investigated the influence of bilateral intra-central
      amygdala (intra-CeA) microinjections of N-methyl-D-aspartate (NMDA) receptor
      agents on amnesia induced by a cannabinoid CB1 receptor agonist,
      arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory
      (passive) avoidance task to assess memory in adult male Wistar rats. The results
      showed that intra-CeA administration of ACPA (2 ng/rat) immediately after
      training decreased inhibitory avoidance (IA) memory consolidation as evidenced by
      a decrease in step-through latency on the test day, which was suggestive of drug
      induced amnesia. Post-training intra-CeA microinjections of NMDA (0.0001, 0.001
      and 0.01 MUg/rat) did not affect IA memory consolidation. However co
      administration of NMDA with ACPA (2 ng/rat) prevented the impairment of IA memory
      consolidation that was induced by ACPA. Although post-training intra-CeA
      administration of the NMDA receptor antagonist, D-(-)-2-amino-5
      phosphonopentanoic acid (D-AP5; 0.01, 0.05 and 0.1 MUg/rat) alone had no effect,
      its co-administration with an ineffective dose of ACPA (1 ng/rat) impaired IA
      memory consolidation. Post-training intra-CeA microinjection of an ineffective
      dose of D-AP5 (0.01 MUg/rat) prevented an NMDA response to the impaired effect of
      ACPA. These results suggest that amnesia induced by intra-CeA administration of
      ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.

PMID- 21740976
TI  - Hormonal contraception usage is associated with altered memory for an emotional
      story.
AB  - Substantial evidence now documents sex-related influences on the neurobiology of
      emotional memory. Robust sex influences exist, for example, on the amygdala's
      role in emotional memory formation, as well as on retention of central
      information (gist) and detail for an emotional event. Evidence also suggests that
      the well-documented effects of stress hormones on memory depend upon sex hormone
      levels. Since hormonal contraception alters sex hormone levels, and must by
      extension alter sex/stress hormone interactions in memory, we examined whether
      the use of hormonal contraception also alters memory for an emotional story. Two
      groups of healthy female subjects--one naturally cycling, one using hormonal
      contraception--viewed either a brief, emotionally arousing story, or a closely
      matched, but more emotionally neutral story. Each subject's eye movements and
      pupil dilation changes were recorded as they viewed the story. Additionally,
      saliva samples were taken throughout the experimental session to examine salivary
      alpha-amylase, a biomarker for norepinephrine. A surprise free recall test one
      week later measured story memory in all subjects. Naturally cycling women
      exhibited enhanced memory of story details, but not of central information
      (gist), in the emotional compared with neutral story conditions. In contrast,
      women using hormonal contraception exhibited enhanced memory of gist, but not
      story details, in the emotional compared with neutral story conditions. Analysis
      of eye movements made while watching the stories indicated that the differences
      in memory could not be attributed either to a differential attention focus or to
      the degree of arousal induced by the stories in the two groups. These findings
      suggest that the use of hormonal contraception alters memory for an emotional
      event, perhaps by altering sex/stress hormone interactions in memory formation.
      They also suggest that further investigation of the mnemonic effects of these
      very widely used treatments is warranted.

PMID- 21740977
TI  - Evidence for transcriptional regulation of the urea transporter in the gill of
      the Gulf toadfish, Opsanus beta.
AB  - Ureotelic Gulf toadfish (Opsanus beta) do not excrete urea continuously; instead,
      urea is accumulated internally until a branchial urea transport mechanism is
      activated to facilitate the excretion of urea in distinct pulses. This unusual
      pulsatile urea excretion pattern is regulated, in part, by permissive declines in
      circulating cortisol concentrations. The current study examined toadfish urea
      transporter (tUT) and glucocorticoid receptor (GR) transcript levels in toadfish
      gill following chronic (days) and acute (hours) changes in corticosteroid
      activity. Experimentally lowering circulating cortisol did not significantly
      alter tUT mRNA abundance but increased GR mRNA. On an acute timescale, a 6.2-fold
      upregulation of tUT mRNA occurred 12 to 18 h following a urea pulse event with no
      change in GR mRNA. In silico analysis of an isolated 1.2 kb fragment, upstream
      promoter region of the tUT gene, revealed 6 putative glucocorticoid response
      element (GRE) half sites. In vivo reporter assays of the tUT promoter fragment
      demonstrated relative luciferase activity was enhanced 3.4- and 9.8-fold
      following exposure to moderate (via a 48 h crowding stress) and high (via
      infusion for 48 h) cortisol. We conclude that a GRE-mediated upregulation of mRNA
      may be required to maintain tUT activity by offsetting post-transcriptional
      and/or post-translational changes that may be associated with chronically
      elevated plasma cortisol.

PMID- 21740978
TI  - Multivariate geometrical analysis of catalytic residues in the penicillin-binding
      proteins.
AB  - Penicillin-binding proteins (PBPs) are bacterial enzymes involved in the final
      stages of cell wall biosynthesis, and are targets of the beta-lactam antibiotics.
      They can be subdivided into essential high-molecular-mass (HMM) and non-essential
      low-molecular-mass (LMM) PBPs, and further divided into subclasses based on
      sequence homologies. PBPs can catalyze transpeptidase or hydrolase
      (carboxypeptidase and endopeptidase) reactions. The PBPs are of interest for
      their role in bacterial cell wall biosynthesis, and as mechanistically
      interesting enzymes which can catalyze alternative reaction pathways using the
      same catalytic machinery. A global catalytic residue comparison seemed likely to
      provide insight into structure-function correlations within the PBPs. More than
      90 PBP structures were aligned, and a number (40) of active site geometrical
      parameters extracted. This dataset was analyzed using both univariate and
      multivariate statistical methods. Several interesting relationships were
      observed. (1) Distribution of the dihedral angle for the SXXK-motif Lys side
      chain (DA_1) was bimodal, and strongly correlated with HMM/transpeptidase vs
      LMM/hydrolase classification/activity (P<0.001). This structural feature may
      therefore be associated with the main functional difference between the HMM and
      LMM PBPs. (2) The distance between the SXXK-motif Lys-NZ atom and the Lys/His
      nitrogen atom of the (K/H)T(S)G-motif was highly conserved, suggesting importance
      for PBP function, and a possibly conserved role in the catalytic mechanism of the
      PBPs. (3) Principal components-based cluster analysis revealed several distinct
      clusters, with the HMM Class A and B, LMM Class C, and LMM Class A K15 PBPs
      forming one "Main" cluster, and demonstrating a globally similar arrangement of
      catalytic residues within this group.

PMID- 21740979
TI  - Families Opisthorchiidae and Heterophyidae: are they distinct?
AB  - Superfamily Opisthorchioidea Looss, 1899 consists of three well-known families,
      Opisthorchiidae, Heterophyidae, and Cryptogonimidae, with basic similarities in
      morphology and life-cycles. Many species in the first two of these families are
      human pathogens, such as Opisthorchis viverrini, O. felineus, Clonorchis
      sinensis, Haplorchis spp. and Metagonimus spp. Recently, a molecular phylogenetic
      study on the classification of Digenea revealed a paraphyletic relationship
      between Opisthorchiidae and Heterophyidae. For our study, we gathered and
      analyzed all available data in GenBank, together with new data of nuclear 18S
      ribosomal DNA and ribosomal internal transcribed spacer 2 (ITS2) sequences of the
      families within the Opisthorchioidea. Maximum likelihood and Bayesian inference
      analyses suggested that families Opisthorchiidae and Heterophyidae are
      inseparable from each other, with the former nested within the latter. Groupings
      in molecular trees are generally consistent with morphological features used in
      taxonomy.

PMID- 21740980
TI  - Parasitological and biochemical parameters in Schistosoma mansoni-infected mice
      treated with methanol extract from the plants Chenopodium ambrosioides, Conyza
      dioscorides and Sesbania sesban.
AB  - This study aims to detect the antischistosomal properties of the plants'
      Chenopodium ambrosioides, Conyza dioscorides and Sesbania sesban methanol extract
      against Schistosoma mansoni in infected mice, including determination of total
      protein and albumin levels and the activities of alanine and aspartate
      transaminases (AlT, AsT) and acid and alkaline phosphatases (AcP and AkP) enzymes
      in the serum of infected treated mice. Male Swiss albino mice were infected with
      S. mansoni and orally treated with methanol extract of the plants C. ambrosioides
      (1250 mg/kg/day), C. dioscorides and S. sesban (1000 mg/kg/day from each) for 2
      consecutive days 7 weeks post infection (PI). In addition, treatment of mice with
      the tested dose of each plant extract was successively done (i.e. the 1st extract
      followed by the 2nd and 3rd one with an hour interval). Parasitological and
      biochemical parameters were assessed. Nine weeks PI, the reduction rates of worm
      load/mouse treated with either C. dioscorides (1000 mg/kg), C. ambrosioides (1250
      mg/kg) or S. sesban (1000 mg/kg) were 40.9%, 53.7% and 54.4%, respectively.
      Successive treatment raised the reduction rates of worm load/mouse to 66.3% and
      the ova/g tissue in liver to 76.9%. Moreover, serum total protein and albumin
      levels and activities of AlT, Ast, AcP and AkP enzymes of infected treated mice
      were improved in comparison with those of infected untreated ones. It is
      concluded that administration of C. dioscorides, C. ambrosioides and S. sesban
      methanol extract to infected mice exhibited a moderate antischistosomal effect.
      Successive treatment improved the antischistosomal properties of these plant
      species, hence ameliorated the liver functions of treated mice that may suggest
      degenerations of liver granulomas and regenerative changes.

PMID- 21740981
TI  - Molecular expression and enzymatic characterization of thioredoxin from the
      carcinogenic human liver fluke Opisthorchis viverrini.
AB  - The human liver fluke, Opisthorchis viverrini, induces inflammation of the
      hepatobiliary system. Despite being constantly exposed to inimical oxygen
      radicals released from inflammatory cells, the parasite survives for years.
      Defense against oxidative damage can be mediated through glutathione and/or
      thioredoxin utilizing systems. Here, we report the molecular expression and
      biochemical characterization of a thioredoxin (Trx) from O. viverrini. O.
      viverrini Trx cDNA encoded a polypeptide of 105 amino acid residues, of molecular
      mass 11.63 kDa. The predicted protein has similarity to previously characterized
      thioredoxins with 26-51% identity. Recombinant O. viverrini Trx (Ov-Trx-1) was
      expressed as soluble protein in E. coli. The recombinant protein showed insulin
      reduction activity and supported the enzymatic function of O. viverrini
      thioredoxin peroxidase. Expression of Ov-Trx-1 at mRNA and protein levels was
      observed in all obtainable developmental stages of the liver fluke. Ov-Trx-1 was
      also detected in excretory-secretory products released by adult O. viverrini.
      Immunohistochemistry, Ov-Trx-1 was expressed in nearly all parasite tissue
      excepted ovary and mature sperms. Interestingly, Ov-Trx-1 was observed in the
      infected biliary epithelium but not in normal bile ducts. These results suggest
      that Ov-Trx-1 is essential for the parasite throughout the life cycle. In the
      host-parasite interaction aspect, Ov-Trx-1 may support thioredoxin peroxidase in
      protecting the parasite against damage induced by reactive oxygen species from
      inflammation.

PMID- 21740982
TI  - High-performance thin-layer chromatography/mass spectrometry for the analysis of
      neutral glycosphingolipids.
AB  - This mini-review summarizes the protocol we have developed for the analysis of
      neutral glycosphingolipids (GSLs) by high-performance thin layer chromatography
      (HPTLC)-mass spectrometry (MS). We also present results obtained using this
      glycolipidomic approach to study neutral GSLs from mouse kidney, spleen, and
      small intestine. Finally, we discuss what is required for further development of
      this method, as well as what is expected for the future of glycolipid biology.

PMID- 21740983
TI  - Mass spectrometric analysis of neutral sphingolipids: methods, applications, and
      limitations.
AB  - Sphingolipids represent an important class among lipids, especially when
      considering their vital roles in lipid metabolism. Thus, a variety of methods
      have been created to accomplish their analysis and the term "sphingolipidomics"
      has recently been coined to underline the motivation to enable a comprehensive
      analysis of all sphingolipid species including the acidic and the neutral ones.
      In this review, we summarize selected mainly biomedical based mass spectrometric
      approaches for the analysis of neutral sphingolipids regarding their advantages,
      applications and limitations. To underline some practical aspects of method
      development, we focus on a new method recently developed in our laboratory, which
      enables separation, detection, and mass spectrometric profiling of ceramide,
      hexosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide,
      sphingomyelin species, and cholesterol in one run. This method can be applied to
      investigate impairments of neutral sphingolipid metabolism in a variety of
      disorders such as sphingolipidoses and be employed to screen for sphingolipid
      profile changes as induced by knockout experiments or related studies.

PMID- 21740984
TI  - Therapy of polymyositis and dermatomyositis.
AB  - Because polymyositis and dermatomyositis (PM/DM) are uncommon conditions, few
      randomized placebo controlled studies have been performed in these patients. The
      first line of therapy consists in high-dose oral prednisone, prescribed at
      1mg/kg/day, then progressively tapered based on patients' clinical response. In
      patients who do not improve with corticosteroids alone, methotrexate is added,
      the therapeutic effect of which being observed within 8weeks. If PM/DM patients
      are refractory to corticosteroids and methotrexate, intravenous immunoglobulins
      can be added. In patients who fail to respond to this therapeutic strategy, it is
      crucial to make sure that the correct diagnosis has been made and we strongly
      recommend to perform a new muscle biopsy in order to exclude other myopathies. If
      the diagnosis of PM/DM is confirmed, a number of therapeutic agents may be
      proposed, including mycophenolate mofetil and rituximab. Importantly, TNF-alpha
      antagonists should not be considered in PM/DM patients, as these agents have been
      shown to favor exacerbation of interstitial lung disease and myositis and
      increase the risk of severe pyogenic and opportunistic infections in PM/DM
      patients.

PMID- 21740985
TI  - Role of NKT cells in autoimmune liver disease.
AB  - The three main broad categories of autoimmune liver disease are autoimmune
      hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing
      cholangitis (PSC). The etiologies of these diseases are still incompletely
      understood, but seem to involve a combination of immune, genetic and
      environmental factors. Although each of these diseases has relatively distinct
      clinical, serologic and histological profiles, all of them share common pathways
      of immune-mediated liver injury. The development of autoimmune liver diseases is
      thought to be due to an imbalance of proinflammatory and anti-inflammatory immune
      responses within the liver, with proinflammatory immune responses being
      upregulated and anti-inflammatory ones downregulated. The available evidence,
      suggest that during autoimmune responses within the liver, "self" antigens are
      presented by antigen presenting cells (APCs) which then activate, directly and/or
      indirectly, NKT cells and other innate immune cells within the liver.
      Importantly, the hepatic innate immune system plays an increasingly recognized
      role in the development and propagation of autoimmune liver injury. NKT cells
      predominantly reside in the liver sinusoids, and through their ability to rapidly
      produce a wide variety of cytokines (e.g. Th1, TH2, Th17 cytokine patterns), are
      a critical checkpoint that bridges innate and adaptive immune responses.
      Specifically, activated NKT cells are capable of transactivating other innate and
      adaptive immune cells within the liver to amplify and regulate subsequent immune
      responses within the liver. It has been hypothesized that NKT cells in the
      setting of autoimmune liver disease can play diverse roles, including driving
      both anti-inflammatory and proinflammatory responses, as well as regulating the
      hepatic recruitment of other types of immunoregulatory cells, including
      regulatory T cells.

PMID- 21740986
TI  - Effects of oral N-acetylcysteine on fatigue, critical power, and W' in exercising
      humans.
AB  - The accumulation of reactive oxygen species (ROS) is associated with muscular
      fatigue. The antioxidant N-acetylcysteine (NAC) can extend time to fatigue (TTF),
      but the effect appears to be exercise intensity dependent. The purpose of this
      study was to determine the effects of an acute oral dose of NAC on time to
      fatigue (TTF), critical power (CP), W' (curvature constant), V(O2) kinetics and
      muscle EMG during cycling exercise. Male (n=7) subjects performed four tests at
      power outputs corresponding to 80, 90, 100, and 110% of the peak power output
      achieved during the incremental test (Pmax) under NAC and placebo (PLA)
      conditions. TTF was increased only in the 80% Pmax trial (p=0.033). CP was higher
      with NAC (NAC: 232+/-28 W versus PLA: 226+/-31 W; p=0.032), but W' tended to
      decrease (NAC: 15.5+/-3.8 kJ versus W': 16.4+/-4.5 kJ; p=0.10). The change in W'
      was negatively related to the change in CP (r = -0.96). MdPF and RMS of EMG
      tended to change less with NAC. There were no significant differences in V(O2)
      kinetics. These results demonstrate that oral NAC was successful in extending
      time to fatigue at 80% Pmax but not at higher work rates.

PMID- 21740991
TI  - Toxicology and risk assessment conference 2009. Toxicology and risk assessment
      from the trenches: an overview.

PMID- 21740987
TI  - Influence of glycosaminoglycan identity on vocal fold fibroblast behavior.
AB  - Poly(ethylene glycol) (PEG) hydrogels have recently begun to be studied for the
      treatment of scarred vocal fold lamina propria due, in part, to their tunable
      mechanical properties, resistance to fibroblast-mediated contraction, and ability
      to be polymerized in situ. However, pure PEG gels lack intrinsic biochemical
      signals to guide cell behavior and generally fail to mimic the frequency
      dependent viscoelastic response critical to normal superficial lamina propria
      function. Recent results suggest that incorporation of viscoelastic bioactive
      substances, such as glycosaminoglycans (GAGs), into PEG networks may allow these
      gels to more closely approach the mechanical responses of normal vocal fold
      lamina propria while also stimulating desired vocal fold fibroblast behaviors.
      Although a number of vocal fold studies have examined the influence of hyaluronan
      (HA) on implant mechanics and vocal fold fibroblast responses, the effects of
      other GAG types have been relatively unexplored. This is significant, since
      recent studies have suggested that chondroitin sulfate C (CSC) and heparan
      sulfate (HS) are substantially altered in scarred lamina propria. The present
      study was therefore designed to evaluate the effects of CSC and HS incorporation
      on the mechanical response of PEG gels and vocal fold fibroblast behavior
      relative to HA. As with PEG-HA, the viscoelasticity of PEG-CSC and PEG-HS gels
      more closely approached that of the normal vocal fold lamina propria than pure
      PEG hydrogels. In addition, collagen I deposition and fibronectin production were
      significantly higher in CSC than in HA gels, and levels of the myofibroblast
      marker smooth muscle alpha-actin (SM alpha-actin) were greater in CSC and HS gels
      than in HA gels. Since collagen I, fibronectin, and SM alpha-actin are generally
      elevated in scarred lamina propria these results suggest that CSC and HS may be
      undesirable for vocal fold implants relative to HA. Investigation of various
      signaling intermediates indicated that alterations in NFkappaB-p50, NFkappaB-p65,
      or pERK1/2 levels may underlie the observed differences among the PEG-GAG gels.

PMID- 21740992
TI  - Disclosing medical errors: a practical guide and discussion of radiation oncology
      specific controversies.

PMID- 21740993
TI  - Dose escalation in the radiation therapy of prostate cancer.

PMID- 21740994
TI  - Microbeam radiation-induced tissue damage depends on the stage of vascular
      maturation.
AB  - PURPOSE: To explore the effects of microbeam radiation (MR) on vascular biology,
      we used the chick chorioallantoic membrane (CAM) model of an almost pure vascular
      system with immature vessels (lacking periendothelial coverage) at Day 8 and
      mature vessels (with coverage) at Day 12 of development. METHODS AND MATERIALS:
      CAMs were irradiated with microplanar beams (width, ~25 MUm; interbeam spacing,
      ~200 MUm) at entrance doses of 200 or 300 Gy and, for comparison, with a broad
      beam (seamless radiation [SLR]), with entrance doses of 5 to 40 Gy. RESULTS: In
      vivo monitoring of Day-8 CAM vasculature 6 h after 200 Gy MR revealed a near
      total destruction of the immature capillary plexus. Conversely, 200 Gy MR barely
      affected Day-12 CAM mature microvasculature. Morphological evaluation of Day-12
      CAMs after the dose was increased to 300 Gy revealed opened interendothelial
      junctions, which could explain the transient mesenchymal edema immediately after
      irradiation. Electron micrographs revealed cytoplasmic vacuolization of
      endothelial cells in the beam path, with disrupted luminal surfaces; often the
      lumen was engorged with erythrocytes and leukocytes. After 30 min, the capillary
      plexus adopted a striated metronomic pattern, with alternating destroyed and
      intact zones, corresponding to the beam and the interbeam paths within the array.
      SLR at a dose of 10 Gy caused growth retardation, resulting in a remarkable
      reduction in the vascular endpoint density 24 h postirradiation. A dose of 40 Gy
      damaged the entire CAM vasculature. CONCLUSIONS: The effects of MR are mediated
      by capillary damage, with tissue injury caused by insufficient blood supply.
      Vascular toxicity and physiological effects of MR depend on the stage of
      capillary maturation and appear in the first 15 to 60 min after irradiation.
      Conversely, the effects of SLR, due to the arrest of cell proliferation, persist
      for a longer time.

PMID- 21740995
TI  - The role of platelet factor 4 in radiation-induced thrombocytopenia.
AB  - PURPOSE: Factors affecting the severity of radiation-induced thrombocytopenia
      (RIT) are not well described. We address whether platelet factor 4 (PF4; a
      negative paracrine for megakaryopoiesis) affects platelet recovery postradiation.
      METHODS AND MATERIALS: Using conditioned media from irradiated bone marrow (BM)
      cells from transgenic mice overexpressing human (h) PF4 (hPF4+), megakaryocyte
      colony formation was assessed in the presence of this conditioned media and PF4
      blocking agents. In a model of radiation-induced thrombocytopenia, irradiated
      mice with varying PF4 expression levels were treated with anti-hPF4 and/or
      thrombopoietin (TPO), and platelet count recovery and survival were examined.
      RESULTS: Conditioned media from irradiated BM from hPF4+ mice inhibited
      megakaryocyte colony formation, suggesting that PF4 is a negative paracrine
      released in RIT. Blocking with an anti-hPF4 antibody restored colony formation of
      BM grown in the presence of hPF4+ irradiated media, as did antibodies that block
      the megakaryocyte receptor for PF4, low-density lipoprotein receptor-related
      protein 1 (LRP1). Irradiated PF4 knockout mice had higher nadir platelet counts
      than irradiated hPF4+/knockout litter mates (651 vs. 328 * 106/mcL, p = 0.02) and
      recovered earlier (15 days vs. 22 days, respectively, p <0.02). When irradiated
      hPF4+ mice were treated with anti-hPF4 antibody and/or TPO, they showed less
      severe thrombocytopenia than untreated mice, with improved survival and time to
      platelet recovery, but no additive effect was seen. CONCLUSIONS: Our studies show
      that in RIT, damaged megakaryocytes release PF4 locally, inhibiting platelet
      recovery. Blocking PF4 enhances recovery while released PF4 from megakaryocytes
      limits TPO efficacy, potentially because of increased release of PF4 stimulated
      by TPO. The clinical value of blocking this negative paracrine pathway post-RIT
      remains to be determined.

PMID- 21740997
TI  - Response to "the impact of pretreatment prostate volume on severe acute
      genitourinary toxicity in prostate cancer patients treated with intensity
      modulated radiation therapy" (Int J Radiat Oncol Biol Phys 2011;79:379-384).

PMID- 21740999
TI  - Long-term results of brachytherapy with temporary iodine-125 seeds in children
      with low-grade gliomas.

PMID- 21741000
TI  - In regard to Brown et al. (Int J Radiat Oncol Biol Phys 2010;78:323-327).

PMID- 21741002
TI  - Perinatal programming of neuropsychiatric disorders.

PMID- 21741003
TI  - Intracellular defenses against HIV, viral evasion and novel therapeutic
      approaches.
AB  - Human immunodeficiency virus (HIV), the causative agent of AIDS, is a retrovirus.
      It is estimated that, while in the cell, it interacts with almost 10% of cellular
      proteins. Several of these have evolved to protect the cell from infection with
      retroviruses and are known as "restriction factors". Restriction factors tell us
      much about how the virus functions and open up new paradigms for exploring novel
      antiviral therapeutics. This article gives an update on the three best studied
      restriction factors, their putative mechanisms of action and how the virus has
      overcome their effects, together with an indication of novel therapeutic
      approaches based on this knowledge.

PMID- 21741004
TI  - Reversal of hypolipidemia in chronic hepatitis C patients after successful
      antiviral therapy.
AB  - BACKGROUND/PURPOSE: Chronic infection with the hepatitis C virus (HCV) is
      associated with impaired lipid metabolism. The aim of this study was to determine
      the impact of antiviral response on the serial change of serum lipids in chronic
      HCV patients. METHODS: A total of 165 consecutive patients with HCV infection
      were prospectively enrolled. Serum total cholesterol (TC) and triglyceride (TG)
      levels in these subjects were compared with age, sex and body mass index-matched
      healthy individuals and 55 patients with chronic infection with hepatitis B virus
      (HBV). Serum lipid levels were measured in 143 patients with chronic HCV
      infection receiving pegylated interferon plus ribavirin therapy at baseline, at
      the end of treatment, and at week 24 after the end of treatment. RESULTS:
      Patients with chronic HCV infection had significantly lower total TC and TG
      levels than normal controls (both p < 0.001). Serum TC levels were lower in HCV
      patients than in those infected with HBV (p < 0.001). Pretreatment serum lipid
      levels were not independent factors associated with sustained virological
      response (SVR). Among patients achieving a SVR, serum TC and TG levels
      significantly increased from 165 +/- 30 mg/dL and 100 +/- 47 mg/dL at baseline to
      191 +/- 36 mg/dL (p < 0.001) and 116 +/- 77 mg/dL (p = 0.029) at week 24
      posttreatment, whereas no evident change in lipid profile occurred in the non-SVR
      group. CONCLUSION: Our data suggest that chronic HCV infection is associated with
      hypocholesterolemia and hypotriglyceridemia, which can be reversed by successful
      eradication of HCV. The clinical significance of hypolipidemia reversal among SVR
      patients, such as the risk of coronary artery or cerebral vascular disease,
      should be further investigated.

PMID- 21741005
TI  - Effect of type 2 diabetes mellitus on the clinical severity and treatment outcome
      in patients with pulmonary tuberculosis: a potential role in the emergence of
      multidrug-resistance.
AB  - BACKGROUND/PURPOSE: A globally increasing trend of type 2 diabetes mellitus (DM),
      the rising prevalence of tuberculosis (TB) in many countries, and the emergence
      of multidrug-resistant TB (MDR-TB) in recent years pose a serious challenge for
      TB control. METHODS: We investigated pulmonary tuberculosis patients with and
      without type 2 DM (DMTB and TB, respectively) treated at the Chest Hospital,
      Taiwan, between November 2004 and October 2005. RESULTS: One hundred and ninety
      two new patients (60 DMTB, 132 TB) were regularly treated for a full course (>= 6
      months) and prospectively followed for more than 1 year. The DMTB patients had
      more severe infections (far-advanced: 45.0%vs. 22.7%, p < 0.01), higher
      mycobacterial loads (sputum smear: 2.9 +/- 1.3(+)vs. 1.9 +/- 1.7(+), p < 0.01),
      higher treatment failure rates (17%vs. 2%, p < 0.01), and longer delayed
      clearance of mycobacteria than did the TB patients (2.5 +/- 3.0 months vs. 1.6 +/
      1.4 months, p < 0.01). After one year, three DMTB patients and one TB patient
      had MDR-TB (5.0%vs. 0.8%, p = 0.056). Bacterial genotyping revealed that the
      proportion of mycobacterial strains was not significantly different in DMTB and
      TB patients (Beijing strain: 46.7%vs. 40.6%, Non-Beijing strain: 53.3%vs. 59.4%,
      p = 0.632). CONCLUSION: DMTB patients have more severe TB infections, which
      require longer treatment and are more likely to develop MDR-TB than are patients
      with TB alone.

PMID- 21741006
TI  - Cyclic vomiting syndrome and migraine in children.
AB  - BACKGROUND: Cyclic vomiting syndrome (CVS) is an episodic nausea and non-bilious
      vomiting disorder characterized by recurrent stereotypic symptoms with disease
      free intervals. CVS in children is associated with a high prevalence of migraine,
      and is commonly considered a precursor to migraine. This study aimed to
      investigate the clinical manifestations of pediatric CVS and its prognosis, and
      to clarify its relationship with the risk of migraine development in children.
      METHODS: The clinical features of children diagnosed with CVS before the age of
      18 years at the designated hospital were retrospectively studied over the past 30
      years (1976-2006) based on the Rome III or ICHD II criteria. Clinical
      evaluations, including age of onset, sex, family history, symptoms and duration
      during attacks, frequency, trigger events, electroencephalogram, treatment and
      subsequent development of migraine were assessed from chart records and telephone
      interviews. RESULTS: Thirty-five children (17 males and 18 females) were
      enrolled. Their age of onset ranged from 2 to 17 years (mean, 6.8 +/- 3.1 years)
      and frequency of attacks ranged from once to 36 times per year (mean, 8.2 +/- 7.6
      times). Duration of symptoms during each attack ranged from 1 to 45 days (mean,
      5.9 +/- 7.3 days). Of 20 children assessed for migraine development, seven
      subsequently developed typical migraine symptoms. There was younger onset age in
      the migraine-positive subgroup (5 +/- 1.7 years) than in the migraine-negative
      subgroup (8.9 +/- 3 years; p = 0.001). Co-morbid headache during CVS attack was
      also more evident in the migraine-positive subgroup (28.6%vs. 0%). CONCLUSION:
      Results of the study show that younger onset age and headache during CVS attacks
      may have increased risk of migraine development. Large-scale prospective studies
      are warranted to further clarify the relationship between CVS and migraine.

PMID- 21741007
TI  - Epidemiological study of hospitalization associated with respiratory syncytial
      virus infection in Taiwanese children between 2004 and 2007.
AB  - BACKGROUND/PURPOSE: Respiratory Syncytial Virus (RSV) is the leading cause of
      hospitalization in young children. The population-based burden of RSV
      hospitalization and the effect of potential risk factors on the severity of
      illness were evaluated in Taiwanese children. METHODS: We analyzed the annual
      population-based incidence, underlying diseases and characteristics of
      hospitalizations due to RSV in Taiwanese children under 5 years of age from 2004
      to 2007 by using Taiwan's National Health Insurance database. RESULTS: A total of
      11,081 children with RSV-associated hospitalization were studied. Average annual
      population-based hospitalization incidence was 1,077 and 232 per 100,000 children
      year in children under 6 months and under 5 years of age, respectively. The peak
      incidence occurred between 1 and 2 months of age. The male-to-female incidence
      risk ratio was 1.4:1 (p < 0.001). There was a significant seasonal distribution
      with consistent peaks in the spring and autumn every year (p < 0.001). A total of
      373 patients (3.3%) had repeated RSV infection. The 943 children (8.5%) with
      underlying diseases were older (p = 0.001), required longer intensive care unit
      (ICU) stays (p < 0.001), had a higher rate of endotracheal intubation (p < 0.05),
      and incurred higher medical costs (p < 0.001). A total of 888 patients (8%)
      required ICU care. Younger age (p < 0.001), prematurity (p < 0.001), cerebral
      palsy (p < 0.001) and congenital heart disease (p < 0.001) were independent
      predictors of requiring ICU care. CONCLUSION: RSV infection occurs biennially
      with peaks in spring and fall in Taiwan. Patients with underlying diseases need
      longer hospital and ICU stays and incur higher medical costs. Younger age,
      prematurity, congenital heart disease and cerebral palsy are predictors of ICU
      care.

PMID- 21741008
TI  - Use of rubber dams during root canal treatment in Taiwan.
AB  - BACKGROUND/PURPOSE: Isolation of teeth with rubber dams is an important procedure
      for infection control in dentistry, especially in endodontic treatment. This
      study surveyed the prevalence of rubber dam usage in nonsurgical root canal
      treatment (RCT) by dentists under the National Health Insurance system in Taiwan.
      METHODS: A total of 1,332 completed RCT cases were randomly selected from a large
      database from the Bureau of National Health Insurance in Taiwan in 2004. The
      radiographs and dental charts of the selected cases were evaluated for the
      prevalence of rubber dam usage in RCT. The frequencies of rubber dam usage for
      RCT by dentists were compared between hospitals and private dental clinics and
      among six different regions in Taiwan. RESULTS: The overall prevalence of rubber
      dam usage for RCT by dentists under the National Health Insurance system in
      Taiwan was 16.5%. The frequency of rubber dam usage for RCT by dentists in
      hospitals (32.8%) was significantly higher than that (10.3%) in private dental
      clinics (p < 0.0001). However, there was no significant difference in the
      frequency of rubber dam usage for RCT by dentists among six different geographic
      regions in Taiwan. CONCLUSION: The prevalence of rubber dam usage for RCT by
      dentists in Taiwan is relatively low. Because rubber dam isolation of an
      endodontically-treated tooth can provide better infection control, increase
      patient protection, and improve treatment efficiency, there is an urgent need to
      advise dentists in Taiwan to use rubber dams for every RCT case.

PMID- 21741009
TI  - Association between provider volume and comorbidity on hospital utilization and
      outcomes of total hip arthroplasty among National Health Insurance enrollees.
AB  - BACKGROUND/PURPOSE: The impact of provider volume, comorbidity and adverse
      outcomes on hospital utilization of total hip arthroplasty (THA) has not yet been
      studied scientifically in Taiwan. This study aimed to examine the relationship
      between surgeon/hospital volume, perioperative complications, acute infections
      and hospital utilization for patients who underwent primary (THA). METHODS: We
      analyzed National Health Insurance (NHI) annual reimbursement data for all
      hospital admissions due to primary THA between January 2005 and December 2006. A
      total of 9335 patients with rheumatoid arthritis, osteoarthritis, avascular
      necrosis and other joint disorders were identified. Multivari-ate regression
      analyses were used to assess the relationship between provider volume and
      hospital utilization and the risk of adverse outcomes. Statistical analyses were
      adjusted for patient age, gender, comorbidity, type of arthritis, as well as
      hospital attributes. RESULTS: Reversed linear associations were found among
      hospital utilization, surgeon volume, and comorbidity score. Patients with acute
      infection tended to stay 8 days more and cost NT$32,451 more than their
      counterparts. Patients with perioperative complication tended to stay 2.30 days
      more and cost NT$15,327 more than their counterparts. Longer hospital stay and
      higher total hospital charge were associated with patient's age and Charlson
      index. CONCLUSIONS: This study revealed that the volume of THAs performed by
      individual surgeons was a more important determinant of hospital utilization than
      hospital volume. Perioperative adverse events were associated with patients' age
      and comorbidity.

PMID- 21741010
TI  - Applying intraoperative insulin level monitoring for tumor removal in a patient
      with recurrent pancreatic multiple insulinomas.

PMID- 21741011
TI  - Immunogenicity and reactogenicity of DTPa-IPV/Hib vaccine co-administered with
      hepatitis B vaccine for primary and booster vaccination of Taiwanese infants.
AB  - Immunogenicity and reactogenicity of the combined diphtheria-tetanus-acellular
      pertussis-inactivated poliovirus-Haemophilus influenzae type b (Hib) conjugate
      vaccine (DTPa-IPV/Hib, InfanrixTM-IPV + Hib) was assessed when co-administered
      with hepatitis B (HBV) vaccine. Seventy healthy infants received DTPa-IPV/Hib at
      1.5, 3.5, 6 and 15-18 months, and HBV at birth, 1.5, 6 and 15-18 months of age.
      Serological responses were assessed. Diphtheria, tetanus, Hib and pertussis
      seroprotection/seropositivity rates were 100% after primary vaccination. Post
      primary immune responses to poliovirus could not be evaluated for technical
      reasons. However, after the booster dose, seroprotection/seropositivity rates,
      including poliovirus, were 100%. Over 95% were seroprotected against HBV. Post
      booster geometric mean antibody concentrations/titers (GMC/GMTs) rose from 14
      fold to 45-fold, indicating effective priming against all antigens, including
      polioviruses. DTPa-IPV/Hib was well tolerated alone or co-administered with HBV.
      No serious adverse events were considered related to vaccination. Primary and
      booster vaccination with combined DTPa-IPV/Hib and HBV was immunogenic and well
      tolerated. Combination vaccines enable vaccine providers to conveniently provide
      routine pediatric immunizations, with minimal discomfort.

PMID- 21741012
TI  - Effect of obesity treatments on eating behavior: psychosocial interventions
      versus surgical interventions. A systematic review.
AB  - OBJECTIVE: (1) To use available research data to estimate the amount of change in
      eating behavior following obesity treatment; (2) To examine how this change
      relates to the amount of change in weight loss after treatment and at follow up.
      A meta-analysis was conducted in September 2009. METHODS: Studies were identified
      through a computer search of articles in the PubMed and PsychInfo databases. Key
      terms entered were obesity, treatment, and eating behavior. Effect sizes (Glass
      d) were calculated according to published procedures. RESULTS: Eighteen studies
      met the inclusion and exclusion criteria, grouped into two categories:
      psychosocial interventions and surgical interventions. For psychosocial
      interventions, we found a medium effect size on eating behavior (d=.73, CI=(.66,
      .90)), and a low effect size on weight (d=.32, CI=(.28, .36)) at posttreatment
      and a low effect size for both outcomes at follow-up (for eating behavior d=.47,
      CI=(.45, .49), for weight d=.37, (CI=.18, .56)). For surgical interventions we
      found large effect sizes on both outcomes (for eating behavior d=1.84, CI=(1.26,
      2.42); for weight d=1.40, CI=(1.25, 1.65)). CONCLUSIONS: Surgical interventions
      have superior results to psychosocial interventions, on both weight loss and
      eating behavior. Implications for treatment of obesity are discussed.

PMID- 21741013
TI  - Development and validation of the Detail and Flexibility Questionnaire (DFlex) in
      eating disorders.
AB  - Whilst neuropsychological testing provides the most accurate profile of cognitive
      functioning, the time consuming nature of individual assessment deems it
      impossible for many research and clinical settings. This paper presents the
      development and validation of the Detail and Flexibility Questionnaire (DFlex), a
      24-item self-report scale measuring two aspects of neurocognitive functioning;
      cognitive rigidity (difficulty with set-shifting/flexibility) and attention to
      detail (weak coherence). Exploratory factor analysis extracted two subscales,
      further confirmed and refined by item response analysis. Both subscales showed
      high internal reliability, construct validity (as compared to relevant subscales
      of the Autistic-Spectrum Quotient) and strong discriminant validity with large
      effect sizes found between both lifetime eating disorder and healthy control
      groups, and between current and recovered anorexia nervosa. We suggest using the
      cognitive rigidity and attention to detail subscales independently to give a
      rough approximation of these two aspects of cognitive style as they manifest in
      the context of everyday life.

PMID- 21741014
TI  - A comparative analysis of Type 2 diabetes and binge eating disorder in a
      bariatric sample.
AB  - An emerging literature has illuminated an important link between Type 2 diabetes
      mellitus (DM) and binge eating disorder (BED) within obese cohorts. However,
      prior work has not examined this relationship specifically in a weight loss
      surgery (WLS) sample or fully explored potential psychosocial factors associated
      with this co-occurrence. Therefore, the present investigation sought to identify
      socio-demographic (i.e. age, education, BMI, ethnicity, gender, age of obesity
      onset) and psychological (i.e. depressive symptoms, hedonic hunger/food locus of
      control beliefs, severity of binge eating-related cognitions) correlates of the
      co-occurrence of Type 2 DM and BED among bariatric surgery candidates. An
      archival sample of 488 patients seeking surgical treatment for clinical obesity
      completed a standard battery of pre-operative psychosocial measures. The presence
      of BED was evaluated using a semi-structured clinical interview based on the DSM
      IV TR (APA, 2000) and was further corroborated by responses on the Questionnaire
      on Eating and Weight Patterns-Revised (QEWP-R; Spitzer, Yanovski, & Marcus,
      1993). Results indicated that 8.2% of the sample was classified as having both
      Type 2 DM and BED concurrently. A multivariate logistic regression model revealed
      that in addition to other psychological (e.g., binge eating-related cognitions,
      hedonic hunger) and demographic variables (i.e. male gender), African American
      ethnicity (OR=3.3: 1.41-7.73) was a particularly robust indicator of comorbid
      status. Findings support and extend previous health disparity research urging
      greater attention to the needs of traditionally underserved, at-risk populations
      seeking treatment for obesity complicated by dysregulated eating and metabolism.
      Additionally, these preliminary results underscore the relevance of considering
      the potential benefits of providing quality comprehensive pre- and post-operative
      psychological care among bariatric patients towards optimizing both short- and
      long-term health and well-being.

PMID- 21741015
TI  - The development and validation of the food craving acceptance and action
      questionnaire (FAAQ).
AB  - Research has suggested that mindfulness and acceptance may be important factors
      in the development, maintenance and treatment of both obesity and eating
      disorders. However, very few scales exist that apply constructs of acceptance and
      mindfulness to eating behavior. A measure of acceptance about food related
      thoughts would be especially beneficial in investigating links between acceptance
      and problematic eating, and in better understanding mechanisms of action of
      effective treatments for obesity and eating disorders. The Food Acceptance and
      Awareness Questionnaire (FAAQ) was developed to measure acceptance of urges and
      cravings to eat or the extent to which individuals might try to control or change
      these thoughts. The FAAQ is a self-report questionnaire made up of ten items each
      rated on a seven-point Likert scale (1=very seldom true to 6=always true). Higher
      scores indicate greater acceptance of motivations to eat. The FAAQ was given to a
      sample of 463 undergraduate students along with several other measures of eating
      behavior and other psychological variables. Concurrent associations with
      variables theorized to be closely linked (Eating Attitudes Test, EAT; the Dutch
      Eating Behavior Questionnaire, DEBQ; body mass index, BMI) and not very closely
      linked (the Depression Anxiety Stress Scale, DASS) were evaluated in order to
      indicate the new scale's convergent and divergent validity. These results
      demonstrated highly significant correlations with these measures in the expected
      direction, with stronger correlations for the theoretically-consistent variables
      than the theoretically-inconsistent variables. Exploratory factor analyses
      confirmed a structural two-factor model. Factor 1 seems to measure one's ability
      to regulate eating despite urges and cravings, and Factor 2 seems to measure
      desire to maintain internal control over eating thoughts. The FAAQ was also
      administered to a separate sample of 29 overweight or obese women enrolled in a
      weight loss program, and found to be predictive of weight loss. Taken together,
      results suggest that the FAAQ is a psychometrically sound instrument which might
      be a valuable tool for assessing acceptance of food related thoughts and urges.

PMID- 21741016
TI  - Effects of stress and coping on binge eating in female college students.
AB  - Limited research exists on the association between stress, coping, and binge
      eating. To address this paucity, this study explores these associations in a
      sample of 147 female college students, an at-risk population for binge eating. We
      hypothesized that emotional and avoidant coping would be positively associated
      with stress and binge eating. Conversely, we expected that rational and detached
      coping would be negatively related to stress and binge eating. Furthermore, we
      expected these coping styles to mediate the relationship between stress and binge
      eating. As predicted, emotion-focused and avoidant coping were positively
      associated with stress and binge eating. Additionally, emotion-focused coping
      partially mediated the relationship between stress and binge eating. However, no
      association was found between stress, rational or detached coping, and binge
      eating. These results are discussed within the context of a negative
      reinforcement model of binge eating. Lastly, the importance of providing evidence
      based treatment for individuals with binge eating symptomology is discussed in
      light of our findings.

PMID- 21741017
TI  - Perceived norms for thinness and muscularity among college students: what do men
      and women really want?
AB  - BACKGROUND: Perceived norms are related to health-related attitudes and
      behaviors, including body image. The current study examined body dissatisfaction
      and perceived norms for thinness and muscularity among male and female college
      students. METHOD: Participants included 842 undergraduate students (64.5% female)
      who completed an online survey assessing body image and other health-related
      attitudes and behaviors. A series of independent sample and paired sample t tests
      were conducted to document sex differences in body dissatisfaction and
      misperceptions of thinness and muscularity norms. RESULTS: Based on pictorial
      ratings, both males and females reported discrepancies between their ideal and
      actual figures. Females perceived other females as significantly thinner and less
      muscular than the actual norms. Males perceived other males as significantly
      heavier than their own figures, but the difference between men's self-reported
      muscularity and perceived norm was not significant. Both males and females
      misperceived opposite-sex attractiveness norms for thinness and muscularity.
      DISCUSSION: Results suggest the importance of evaluating same-sex and opposite
      sex perceived norms of thinness and muscularity in the etiology of body
      dissatisfaction, and this research informs social norms interventions targeting
      misperceptions of body image norms among both males and females.

PMID- 21741018
TI  - The role of perfectionism, dichotomous thinking, shape and weight overvaluation,
      and conditional goal setting in eating disorders.
AB  - This study examined the role of perfectionism (self-oriented and socially
      prescribed), shape and weight overvaluation, dichotomous thinking, and
      conditional goal setting in eating disorder psychopathology. Perfectionism and
      shape and weight overvaluation have had longstanding implication in the
      development and maintenance of eating disorders. A leading evidence-based theory
      of eating disorders (Fairburn, Cooper & Shafran, 2003) outlines perfectionism as
      a maintaining mechanism of eating disorder psychopathology and as a proximal risk
      factor for the development of shape and weight overvaluation. These constructs
      have been linked to other cognitive processes relevant to eating disorders,
      specifically, dichotomous thinking and conditional goal setting. Women with DSM
      IV eating disorders (N=238) were compared to women in the general community
      (N=248) and, as hypothesised, scores on measures of these constructs were
      pronounced in the clinical sample. Hierarchical regression analyses predicting
      eating disorder psychopathology showed that for both groups, dichotomous thinking
      and conditional goal setting significantly improved model fit beyond
      perfectionism and shape and weight overvaluation alone. Self-oriented
      perfectionism, but not socially prescribed perfectionism, was relevant to eating
      disorder psychopathology. We discuss the implications for current treatment
      protocols and early intervention.

PMID- 21741019
TI  - Implicit internalization of the thin ideal as a predictor of increases in weight,
      body dissatisfaction, and disordered eating.
AB  - The freshman year of college has been identified as a time when some students
      experience large changes in their eating behaviors, body image, and weight. One
      factor that is predictive of changes in these variables is internalization of the
      thin ideal (i.e., the degree to which an individual has accepted societal values
      of thinness and applies these values to herself). However, given the limitation
      of self-report and previous research demonstrating the additional predictive
      validity implicit measurement provides, it may be important to develop an
      implicit paradigm for assessing internalization of the thin ideal. The Implicit
      Association Test is the most common implicit measurement technique. However this
      test is associational in nature, which reflects only one aspect of human
      cognition. The current study evaluates a newly-created implicit measure of
      internalization of the thin ideal that utilizes the Implicit Relational
      Assessment Procedure (IRAP). In particular, the study investigates concurrent and
      prospective associations between internalization of the thin ideal and disordered
      eating, body image dissatisfaction, and weight in a group of women at the
      beginning and end of their freshman year in college. Results of the study
      indicate that weight, disordered eating and body image dissatisfaction increased
      during the freshman year, and that these were predicted by implicit
      internalization of the thin ideal at the beginning of the year. Moreover, the new
      implicit measure was predictive above and beyond any predictive ability of the
      explicit measure. Results indicate that the thin ideal IRAP can successfully
      predict changes in many variables of interest at the freshman year of college,
      and suggest it may be a beneficial screening tool to assess at-risk freshman.
      This study also highlights the need for additional implicit measures in the realm
      of body image and disordered eating.

PMID- 21741020
TI  - Slow rates of habituation predict greater zBMI gains over 12 months in lean
      children.
AB  - Slow rates of habituation are cross-sectionally related to greater energy intake
      and body weight. The present study is designed to assess whether slow rates of
      habituation are prospectively related to zBMI change over a 12 month period in 66
      lean 8-12 year-old children, and whether the rate of habituation is a stable
      behavioral phenotype. Results showed that slower rates of habituation predicted
      greater zBMI change, controlling for child sex, age, initial zBMI, dietary
      awareness and minority status. In addition, the rate of habituation was stable
      over the year of observation. These data suggest that slow rates of habituation
      may be a risk factor for weight gain and the development of obesity. Future
      research is needed to understand the mechanism for this effect, and assess
      whether the habituation phenotype interacts with other behavioral phenotypes,
      such as food reinforcement, to influence increases in zBMI.

PMID- 21741021
TI  - The temporal dynamics of ambivalence: changes in positive and negative affect in
      relation to consumption of an "emotionally charged" food.
AB  - Ambivalence is thought to impact consumption of food, alcohol and drugs, possibly
      via influences on craving, with cravers often being simultaneously drawn toward
      and repelled from ingestion. So far, little is known about the temporal dynamics
      of ambivalence, especially as it varies in relationship to consumption.
      Participants (n=482, 56.8% female) completed the Positive and Negative Affect
      Schedule prior to, immediately and 30 min after the opportunity to eat a bar of
      chocolate. Affective ambivalence was calculated based on the relative strengths
      of and discrepancy between ratings of positive and negative affect. Ambivalence
      peaked prior to a decision about consumption and subsequently decreased, whether
      or not the decision was in favor of or against consuming. Decreasing ambivalence
      was driven by a drop in positive affect over time; positivity decreased more
      rapidly in those who consumed chocolate. Findings represent a first step in
      characterizing the dynamics of ambivalence in interactions with a target
      stimulus.

PMID- 21741022
TI  - Women's global self-determination, eating regulation, and body dissatisfaction:
      exploring the role of autonomy support.
AB  - Body dissatisfaction is an important correlate of dysfunctional eating. In the
      present study (N=208) the primary aim was to test whether women's internal and
      autonomous motivation can protect against endorsements of societal pressures
      regarding the ideal female body and against body dissatisfaction. Additionally,
      the role of others' autonomy support was investigated. Women who reported more
      Global Self-Determination (GSD) were lower in internalisation of the thin ideal
      and this association was fully mediated by perceived sociocultural pressure to be
      thin. Moreover, the positive association between perceived pressure and body
      dissatisfaction was partially mediated by thin ideal internalisation. Body
      dissatisfaction was associated with a more controlled regulation of eating, and
      GSD moderated the association between body dissatisfaction and autonomous
      regulation of eating. Autonomy support played a role in eating regulation as
      women with more support reported more autonomous eating. Yet, the support did not
      moderate the relationship between body dissatisfaction and eating regulation.
      Future studies should continue to explore the potential facilitative role of
      autonomy support in promoting a self-determined approach to eating regulation.

PMID- 21741023
TI  - College students' definitions of an eating "binge" differ as a function of gender
      and binge eating disorder status.
AB  - Males and females engage in comparable rates of binge eating, but gender
      differences in what constitutes a "binge" may contribute to the disproportionate
      likelihood of females meeting diagnostic criteria for binge eating disorder
      (BED). Using data from one university enrolled in the 2010 Healthy Minds Study,
      we investigated the differences in "eating binge" definitions as a function of
      gender, BED status, and their interaction. This sample of 969 undergraduate
      college students was 64.0% female, and 9.3% (10.7% of women; 6.9% of males) met
      the screening criteria for BED. Open-ended responses defining a "binge" were
      coded into psychological/behavioral and food themes. Females with BED were most
      likely to mention loss of control when defining an eating binge, and relative to
      males with BED, they were significantly more likely to mention sweet foods; males
      with BED were significantly more likely to mention pizza. Findings suggest that
      among those without BED, females mentioned mood, type of food, and engaging in
      compensatory behaviors significantly more often than males. Results suggests that
      the diagnostic emphasis on binge eating as involving "loss of control" may lead
      to a heightened diagnosis of BED among females, yet both genders may experience a
      comparable weight-related sequelae from binge eating.

PMID- 21741024
TI  - What predicts drive for muscularity in college students?
AB  - While research has established that men tend to exhibit greater levels of DFM
      than women, little research has examined the relation between DFM and other forms
      of disordered eating and exercise behaviors. Study 1 examined the influence of
      disordered eating and obligatory exercise on DFM in male and female college
      students. In women, DFM was related to eating concern and obligatory exercise;
      whereas in men, DFM was related to obligatory exercise and shape concern. Study 2
      examined the influence of exercise motivations and body dissatisfaction on DFM in
      male and female college students. In women, DFM was predicted by personal goal
      achievement exercise motives, exercising to cope, and dissatisfaction with
      specific body areas. In men, DFM was predicted by appearance orientation,
      personal goal achievement, affiliation, and recognition exercise motives.

PMID- 21741025
TI  - Evaluation of multislice computed tomography early after transcatheter aortic
      valve implantation with the Edwards SAPIEN bioprosthesis.
AB  - Currently, imaging assessment of patients who undergo transcatheter aortic valve
      implantation is based mainly on echocardiography and angiography, both limited to
      provide a 3-dimensional evaluation of the prosthesis within the native valve.
      This study involved 34 patients who underwent multislice computed tomography
      (MSCT) after transcatheter aortic valve implantation. Prosthesis expansion and
      circularity, depth of implantation, apposition degree at the ventriculoaortic
      junction, and positioning in relation to coronary artery ostia were evaluated.
      Early clinical events such as aortic regurgitation and periprocedural conduction
      abnormalities were recorded and correlated with multislice computed tomographic
      findings. MSCT provided comprehensive 3-dimensional assessments of the prostheses
      in 31 of 34 of patients (91%). Expansion was excellent (mean expansion ratio
      100.0 +/- 10.4%) and increased significantly from the ventricular side to the
      aortic side of the prosthesis. Circular deployment was achieved in most patients
      and increased from the ventricular to the aortic side. Mean implantation depth
      was -2.4 +/- 2.5 mm, associated with a low rate (12%) of permanent pacemaker
      implantation. Patients with a new conduction abnormalities had the deepest
      prosthesis implantation, associated with lesser expansion and circularity.
      Perfect apposition on MSCT was associated with a low rate of significant aortic
      regurgitation. In conclusion, MSCT is able to provide an accurate 3-dimensional
      evaluation of prosthesis deployment and positioning after transcatheter aortic
      valve implantation. Moreover, these anatomic findings correlate with the most
      frequent early complications (i.e., the occurrence of aortic regurgitation and
      conduction abnormalities).

PMID- 21741026
TI  - Propensity score-matched analysis of effects of clinical characteristics and
      treatment on gender difference in outcomes after acute myocardial infarction.
AB  - The greater mortality observed in women compared to men after acute myocardial
      infarction remains unexplained. Using an analysis of pairs, matched on a
      conditional probability of being male (propensity score), we assessed the effect
      of the baseline characteristics and management on 30-day mortality. Consecutive
      patients were included from January 2006 to December 2007. Two propensity scores
      (for being male) were calculated, 1 from the baseline characteristics and 1 from
      both the baseline characteristics and treatment. Two matched cohorts were
      composed using 1:1 matching and computed using the best 8 digits of the
      propensity score. Paired analyses were performed using conditional regression
      analysis. During the study period, 3,510 patients were included in the registry;
      1,119 (32%) were women. Compared to the men, the women were 10 years older, had
      more co-morbidities, less often underwent angiography and reperfusion, and
      received less medical treatment. The 30-day mortality rate was 12.3% (130 of
      1,060) for the women and 7.2% (167 of 2,324) for the men (p <0.001). The 2
      matched populations represented 1,298 and 1,168 patients. After matching using
      the baseline characteristics, the only difference in treatment was a lower rate
      of angiography and reperfusion, with a trend toward greater 30-day mortality in
      women. After matching using both baseline characteristics and treatment, the 30
      day mortality was similar for the men and women, suggesting that the increased
      use of invasive procedures in women could potentially be beneficial. In
      conclusion, compared to men, the 30-day mortality is greater in women and
      explained primarily by differences in baseline characteristics and to a lesser
      degree by differences in management. The difference in the use of invasive
      procedures persisted after matching by characteristics. In contrast, after
      matching using the baseline characteristics and treatment, the 30-day mortality
      was comparable across the genders.

PMID- 21741027
TI  - Indian Siddis: African descendants with Indian admixture.
AB  - The Siddis (Afro-Indians) are a tribal population whose members live in coastal
      Karnataka, Gujarat, and in some parts of Andhra Pradesh. Historical records
      indicate that the Portuguese brought the Siddis to India from Africa about 300
      500 years ago; however, there is little information about their more precise
      ancestral origins. Here, we perform a genome-wide survey to understand the
      population history of the Siddis. Using hundreds of thousands of autosomal
      markers, we show that they have inherited ancestry from Africans, Indians, and
      possibly Europeans (Portuguese). Additionally, analyses of the uniparental (Y
      chromosomal and mitochondrial DNA) markers indicate that the Siddis trace their
      ancestry to Bantu speakers from sub-Saharan Africa. We estimate that the
      admixture between the African ancestors of the Siddis and neighboring South Asian
      groups probably occurred in the past eight generations (~200 years ago),
      consistent with historical records.

PMID- 21741028
TI  - Heparin protects against septic mortality via apoE-antagonism.
AB  - BACKGROUND: Apolipoprotein E (apoE), a component of plasma lipoproteins,
      increases septic mortality in a rodent model of sepsis, presumably by enhancing
      lipid antigen presentation to antigen-presenting cells via the low-density
      lipoprotein receptor (LDLR). Downstream, this culminates in natural killer T
      (NKT) cell activation and cytokine secretion. To determine whether apoE
      antagonism would protect against septic mortality in mice, apoE-LDLR binding was
      antagonized using heparin, which can inhibit apoE's LDLR-binding site. METHODS:
      C57BL/6 mice underwent cecal ligation and puncture (CLP) and heparin infusion.
      Serum partial thromboplastin time and alanine aminotransferase were measured at
      24 hours, and survival was monitored for 7 days after CLP. LDLR+/+ and LDLR-/-
      fibroblasts were incubated with apoE and heparin to measure apoE internalization.
      Hepatic NKT cells and cytokine levels were quantified via fluorescence-activated
      cell sorting. RESULTS: Heparin decreased CLP-induced mortality by 50% versus
      saline-treated controls, independent of anticoagulation. LDLR+/+ fibroblasts
      displayed decreased uptake of apoE when treated concurrently with heparin for 12
      hours. In septic mice, hepatic alanine aminotransferase levels, hepatic NKT
      cells, and plasma cytokine levels decreased after heparin treatment. CONCLUSIONS:
      This study demonstrates that heparin protects against septic mortality
      independent of its anticoagulant effect. This protective effect is associated
      with the inhibition of apoE-LDLR binding, diminished NKT proliferation and
      cytokine production, and hepatic dysfunction. These findings indicate a potential
      clinical role for apoE antagonism in the treatment of sepsis.

PMID- 21741029
TI  - Increased serum brain-derived neurotrophic factor is predictive of cocaine
      relapse outcomes: a prospective study.
AB  - BACKGROUND: Cocaine dependence is associated with high relapse rates, but few
      biological markers associated with relapse outcomes have been identified.
      Extending preclinical research showing a role for central brain-derived
      neurotrophic factor (BDNF) in cocaine seeking, we examined whether serum BDNF is
      altered in abstinent, early recovering, cocaine-dependent individuals and whether
      it is predictive of subsequent relapse risk. METHODS: Serum samples were
      collected across three consecutive mornings from 35 treatment-engaged, 3-week
      abstinent cocaine-dependent inpatients (17 males/18 females) and 34
      demographically matched hospitalized healthy control participants (17 males/17
      females). Cocaine-dependent individuals were prospectively followed on days 14,
      30, and 90 posttreatment discharge to assess cocaine relapse outcomes. Time to
      cocaine relapse, number of days of cocaine use (frequency), and amount of cocaine
      use (quantity) were the main outcome measures. RESULTS: High correlations in
      serum BDNF across days indicated reliable and stable serum BDNF measurements.
      Significantly higher mean serum BDNF levels were observed for the cocaine
      dependent patients compared with healthy control participants (p < .001). Higher
      serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard
      ratio: 1.09, p < .05), greater number of days (p < .05), and higher total amounts
      of cocaine used (p = .05). CONCLUSIONS: High serum BDNF levels in recovering
      cocaine-dependent individuals are predictive of future cocaine relapse outcomes
      and may represent a clinically relevant marker of relapse risk. These data
      suggest that serum BDNF levels may provide an indication of relapse risk during
      early recovery from cocaine dependence.

PMID- 21741030
TI  - Neural changes associated with treatment outcome in children with externalizing
      problems.
AB  - BACKGROUND: The current study directly investigated whether changes in the neural
      correlates of self-regulation (SR) are associated with the effectiveness of
      treatment for the externalizing problems of children. METHODS: Seventy-one
      children 8-12 years of age with clinical levels of externalizing behavior and
      their families completed a 3-month cognitive behavioral therapy program with a
      parent management training component. Electroencephalogram correlates of SR were
      evaluated before and after treatment with a go/no-go task requiring inhibitory
      control. RESULTS: Results showed that neural markers of SR, such as the N2 and
      frontal P3 event-related potential magnitudes, differed between the clinical
      sample and a matched comparison group before treatment: the clinical sample had
      larger N2 magnitudes and smaller frontal P3 magnitudes. Children who improved
      with treatment demonstrated a marked decrease in the magnitude of the N2 in
      comparison with children who did not improve. For improvers only, source analyses
      during the time period of the N2 estimated activation decreases in medial and
      ventral prefrontal cortex as well as the anterior medial temporal lobe.
      CONCLUSIONS: A decrease in N2 magnitudes and corresponding source activation in
      children who improved with treatment might reflect improved efficiency in the
      neural mechanisms of SR.

PMID- 21741031
TI  - Cue-induced reactivity, cortisol response and substance use outcome in treated
      heroin dependent individuals.
AB  - BACKGROUND: Environmental stimuli associated with drug taking have been known to
      elicit drug craving and physiologic arousal, as well as hypothalamic-pituitary
      adrenal axis activation. However, the relationship between these responses and
      substance use outcomes in heroin-dependent subjects has not been previously
      studied. We investigated the relationship among subjective and physiologic
      reactivity, biological stress response evoked in the laboratory, and relapse to
      substance use in treated opiate-dependent individuals. METHODS: Eighteen opiate
      abstinent methadone- or buprenorphine-treated patients and 13 control subjects
      were exposed to neutral- and drug-cue exposure laboratory sessions with a 3-month
      follow-up period. Exposure to cues involved both videotapes and handling during a
      100-min session. Subjective craving, agonistic effects, withdrawal feelings,
      galvanic skin resistance, and salivary cortisol were assessed. Substance use
      outcome among patients was examined during the follow-up phase. Differences
      between relapsers, nonrelapsers, and controls were analyzed with respect to the
      data on drug-cue responsivity and on cortisol responses using repeated-measures
      analysis of variance. The association with substance use outcome was assessed
      using a nominal logistic model. RESULTS: Relapsers experienced greater drug-cue
      induced subjective responses and an increased cortisol response compared with
      both nonrelapsers and control subjects. After adjusting on covariates, cue
      induced cortisol response was associated with the relapser group and was highly
      correlated with self-reports of "high." CONCLUSIONS: Subjects defined as
      relapsers presented a higher cue-induced reactivity during the drug-cue exposure
      as well as an increased cortisol response to drug cues. Higher cortisol response
      to drug cues may increase relapse vulnerability in stable-dose buprenorphine or
      methadone-maintained subjects.

PMID- 21741032
TI  - The function of the adrenocortical axis in permanent middle cerebral artery
      occlusion: effect of glucocorticoids on the neurological outcome.
AB  - We characterized the effect of acute ischemic stroke on the activation of the
      hypothalamic-pituitary-adrenal (HPA) axis and evaluated the role of
      glucocorticoids (GC) in the clinical outcome following ischemic stroke. Male
      spontaneous hypertensive rats underwent permanent middle cerebral artery
      occlusion (PMCAO) and developed a cortical infarct. At 4h post-PMCAO or sham
      operation, serum levels of ACTH and corticosterone (CS) were elevated 5 and 4
      fold respectively as compared to controls and then returned to basal levels at
      24h post surgery. In these experimental groups we found also a significant
      depletion of median eminence (ME)-CRH(41). In adrenalectomized (Adx) rats that
      underwent PMCAO the degree of motor disability and infarct volume was similar to
      that of intact rats. Administration of dexamethasone (Dex) to Adx-PMCAO rats
      significantly improved the motor disability and decreased the infarct volume.
      However, in sham-Adx with PMCAO, Dex had no effect on these two parameters. In
      rats with PMCAO or sham-PMCAO, brain production of PGE(2) was significantly
      increased. This effect was further enhanced in Adx-PMCAO rats and significantly
      inhibited by Dex. In conclusion, activation of the HPA axis following PMCAO is
      due to stress induced by surgery. This activation is mediated by hypothalamic
      CRH(41). Absence of endogenous GC or administration of Dex in naive rats does not
      alter motor and pathological parameters in the acute stage following PMCAO. In
      contrast, administration of Dex significantly improved the outcome following
      cerebral ischemia in Adx rats which may be due to increased glucocorticoid
      receptors. Brain production of PGE(2) does not play an important role in the
      pathophysiology of the acute phase of cerebral ischemia.

PMID- 21741033
TI  - A unique transcriptome at the brain-environment interface: local translation in
      the rat olfactory epithelium.
AB  - All olfactory epithelium cells, including rapidly self-renewing olfactory sensory
      neurons (OSN), are continuously subjected to external airborne aggressions. We
      hypothesized that the apical part of rat olfactory epithelia (AOE) could be the
      site of a local translation to be able to respond rapidly to external stimuli. We
      purified significant amounts of mRNAs from AOE. Sequencing of the cDNA library
      identified 348 mRNA species. Of these, the 220 AOE transcripts encoding proteins
      with known biological functions were classified in functional groups. The main
      functional class (40%) coded for defense, detoxification, anti-oxidant stress and
      innate immunity. Other classes comprised mRNAs encoding functions for neuronal
      metabolism and life (19%), nuclear transcription control (15%), cell survival and
      proliferation (13%), RNA processing and translation (12%). They did not contain
      any known members of the olfactory transduction pathway. The expression of a sub
      set of AOE transcripts was investigated in sub-cellular AOE fractions highly
      enriched in ciliated dendrites and in AOE fractions after forced hemilateral OSN
      specific degeneration. All the mRNAs tested were found to be: i) present in
      enriched ciliated dendrite preparations ii) down-regulated after OSN degeneration
      iii) co-purified with polysomal fractions, suggesting their commitment to local
      translation. We provide strong evidence that the extreme apical side of the
      olfactory epithelium expresses a unique transcriptome, whose function is not
      related to olfaction but mainly to defense and survival. The possible local
      translation of this transcriptome is demonstrated, in supporting cells as well as
      in olfactory neuron ciliated dendrites.

PMID- 21741034
TI  - Differences in self- and other-induced Mu suppression are correlated with
      empathic abilities.
AB  - Recent research suggests a role of the human mirror neuron system in empathic
      processing. Electroencephalographic (EEG) mu suppression in the 8-13Hz band-range
      has been proposed to reflect mirror-like activation of sensorimotor cortices. We
      therefore investigated the relationship between suppression in the 8-13Hz range
      and empathic abilities as measured by the Interpersonal Reactivity Index (IRI).
      Based on previous work showing significant differences between execution- and
      observation-related mu suppression and on theories of empathy pointing to the
      importance of discriminating self from other, we predicted that the size of this
      difference within individuals would correlate with participants' perspective
      taking abilities. Larger differences in execution- and observation-induced mu
      suppression were associated with greater scores on the perspective-taking
      subscale of the IRI. The current data are therefore consistent with the claim
      that neural activity reflected in mu suppression is related to empathic
      abilities.

PMID- 21741035
TI  - B cell infiltration is associated with the increased IL-17 and IL-22 expression
      in the lungs of patients with tuberculosis.
AB  - Although it has been recognized that ectopic follicle-like B cell aggregate
      formation is common in the lungs of patients with tuberculosis, the role of
      infiltrated B cells in human tuberculosis remains to be elucidated. In the
      present study, we showed that ectopic B cell aggregate formation was associated
      with containment of Mycobacterium tuberculosis. The area ratio of ectopic B cell
      aggregates was correlated with localized IL-17 mRNA expression and peripheral TGF
      beta and IL-6 mRNA expression. Depletion of B cells from pleural fluid
      mononuclear cells resulted in significantly diminished M. tuberculosis antigen
      specific IL-17 and IL-22 production, but not in IFN-gamma secretion. Therefore,
      ectopic lung B cell formation is important for containment of M. tuberculosis,
      and up-regulation of IL-17 and IL-22 responses may be an important mechanism
      underlying the protective role B cells in human tuberculosis.

PMID- 21741036
TI  - NKT ligand-loaded, antigen-expressing B cells function as long-lasting antigen
      presenting cells in vivo.
AB  - We had previously shown that activated NKT cells licensed B cells to be
      immunogenic antigen-presenting cells and helped to elicit a wide spectrum of
      cancer targeted immune responses. In the current study, we sought to verify the
      safety of alphaGalCer-loaded, and adenovirus-transduced B cell-based vaccines,
      together with mechanism of action. Intravenously injected alphaGalCer-loaded,
      antigen-expressing B cells rapidly localized in the spleen and directly primed
      CD8(+) T cells in an antigen-specific manner. The transferred antigen was
      sustained for at least 30 days. While some injected B cells produced nonspecific
      IgG, the antigen-specific IgG response was completely dependent on endogenous B
      cells. The liver was one of the main tissues where injected B cells were
      retained; however, we could not find the signs of liver toxicity. Our results
      demonstrate that alphaGalCer-loaded, antigen-expressing B cells behave as
      "antigen-presenting" cells that stimulate endogenous antigen-specific T cells and
      B cells in vivo without significant toxicity.

PMID- 21741037
TI  - Smoking for weight control and its associations with eating disorder
      symptomatology.
AB  - OBJECTIVE: This study examined interrelationships between cigarette smoking for
      weight control and eating disorder symptoms in a community sample of adult female
      smokers. METHOD: Participants were 107 female smokers who completed a battery of
      questionnaires, including the Eating Disorder Examination-Questionnaire (EDE-Q).
      Key items measured weight-control smoking, including smoking to prevent
      overeating, smoking to undo the effects of overeating, and smoking to feel less
      hungry. Smokers who endorsed smoking in an attempt to control weight were
      compared with those who denied such behaviors on EDE-Q scores and frequency of
      binge eating and purging. RESULTS: A substantial proportion of participants
      reported weight-control smoking. Participants who endorsed weight-control smoking
      reported elevations on eating disorder symptoms as measured by the EDE-Q.
      Compensatory smoking was related to the frequency of binge eating. DISCUSSION:
      The findings have implications for clinicians working with eating disorder
      patients; for some individuals, cigarette smoking may be used as an attempt to
      compensate for overeating.

PMID- 21741038
TI  - Dissociative symptoms in patients with schizophrenia: relationships with
      childhood trauma and psychotic symptoms.
AB  - OBJECTIVE: This study sought to examine the stability of dissociative symptoms in
      patients with schizophrenia spectrum disorders as well as relationships between
      psychotic symptoms, childhood trauma, and dissociation. METHOD: One hundred forty
      five patients with schizophrenia spectrum disorders (72% schizophrenia, 67% men)
      were examined at admission to inpatient treatment and 3 weeks later using the
      Positive and Negative Syndrome Scale, the Childhood Trauma Questionnaire, and the
      Dissociative Experiences Scale. RESULTS: Dissociative symptoms significantly
      decreased over time (mean, 19.2 vs 14.1; P < .001). The best predictor of
      dissociative symptoms at admission was the Positive and Negative Syndrome Scale
      positive subscale (F(inc)(3,64) = 3.66, P = .017), whereas childhood sexual abuse
      best predicted dissociation when patients were stabilized (F(inc)(10,80) = 2.00,
      P = .044). CONCLUSION: Dissociative symptoms in patients with schizophrenia
      spectrum disorders are related to childhood trauma. Dissociation seems to be
      state dependent in this diagnostic group. Moreover, diagnostic interviews, in
      addition to the Dissociative Experiences Scale, should be considered to avoid
      measurement artifacts.

PMID- 21741039
TI  - Depressive dimensions and item response analysis of the Hamilton Depression
      Rating Scale-17 in eating disorders.
AB  - BACKGROUND: Most patients having eating disorders (EDs) experience depressive
      symptoms. To date, there have been few reports about the different depressive
      dimensions in EDs. OBJECTIVE: The aim of this study was to investigate the
      dimensions of depressive symptoms and highlight the distribution of the symptoms.
      The psychometric properties of these measures were tested using item response
      theory methods. METHODS: A total of 103 consecutively admitted inpatients and
      outpatients who met the Diagnostic and Statistical Manual of Mental Disorders,
      Revised Fourth Edition, criteria for anorexia nervosa, bulimia nervosa, and EDs
      not otherwise specified were rated with the Hamilton Depression Rating Scale
      (HDRS-17). A factor analysis of the HDRS-17 was carried out with the Cf-varimax
      rotation. RESULTS: Factor analysis showed 2 independent and clinically
      interpretable factors corresponding to "anxious depression" and "somatic
      complaints" that constituted the core of depression. For the HDRS-17, item
      response theory analyses revealed that most of the items were maximally related
      to the core concept of depression and provided a good functioning. The 17 items
      were distributed in almost the same way as in the factor analyses found by other
      authors with different clinical groups. We conclude therefore that for the sample
      of EDs, 2 factors constitute the core symptoms of depression and most of the
      items provided a good functioning.

PMID- 21741040
TI  - Modeling of heart systolic murmurs based on multivariate matching pursuit for
      diagnosis of valvular disorders.
AB  - Heart murmurs are pathological sounds produced by turbulent blood flow due to
      certain cardiac defects such as valves disorders. Detection of murmurs via
      auscultation is a task that depends on the proficiency of physician. There are
      many cases in which the accuracy of detection is questionable. The purpose of
      this study is development of a new mathematical model of systolic murmurs to
      extract their crucial features for identifying the heart diseases. A high
      resolution algorithm, multivariate matching pursuit, was used to model the
      murmurs by decomposing them into a series of parametric time-frequency atoms.
      Then, a novel model-based feature extraction method which uses the model
      parameters was performed to identify the cardiac sound signals. The proposed
      framework was applied to a database of 70 heart sound signals containing 35
      normal and 35 abnormal samples. We achieved 92.5% accuracy in distinguishing
      subjects with valvular diseases using a MLP classifier, as compared to the
      matching pursuit-based features with an accuracy of 77.5%.

PMID- 21741041
TI  - Short review: field recovery and potential information value of small elements of
      the skeleton.
AB  - The recovery of small elements of the skeleton (e.g. hyoid, carpals, and hand and
      foot phalanges) is one of the established tasks of the archaeologist and physical
      anthropologist when working in the field, whether in an archaeological or
      forensic context. In the present work, we illustrate the field location of
      ossified laryngeal cartilages, hand sesamoids, and the medial clavicular
      epiphyses. The potential information offered by these elements is briefly
      summarized. The frequency of these elements observed in a cemetery dating from
      1943 indicates the possibility that these elements could be found in other
      contexts at a higher frequency than expected.

PMID- 21741042
TI  - Accuracy of burn size assessment prior to arrival in Dutch burn centres and its
      consequences in children: a nationwide evaluation.
AB  - BACKGROUND: Total body surface area (TBSA) burned, expressed as percentage is one
      of the most important aspects of the initial care of a burn victim. It determines
      whether transfer to a burn centre is necessary as well as the need for, and
      amount of, intravenous fluid resuscitation. Numerous studies, however, have
      highlighted inaccuracies in TBSA assessment. Therefore, the differences in burn
      size estimates between referrers and burn centre's in children and its
      consequences in terms of transfer and intravenous fluid resuscitation were
      investigated. METHODS: This study involved two time periods from January 2002
      until March 2004 and January 2007 until August 2008. All referred children
      admitted to a Dutch Burn centre within 24h post burn were eligible. Data were
      obtained from patient records retrospectively and in part prospectively. RESULTS:
      A total of 323 and 299 children were included in periods 1 and 2, respectively.
      Referring physicians overestimated burn size with a factor two (mean difference:
      6% TBSA +/- 5.5). About one in five children was referred to a burn centre
      without fulfilling the criteria for referral with regard to burn size (assessed
      by burn specialists) special localisation or inhalation trauma. Proportions of
      children receiving intravenous fluid resuscitation regardless of indication
      increased from 33% to 49% (p<0.01). The received volumes tended to be higher than
      necessary. CONCLUSIONS: Referring physicians overestimate burn size in children
      admitted to Dutch burn centres. This has little negative consequences, however,
      in terms of unindicated transfers to a burn centre or unnecessary fluid
      resuscitation.

PMID- 21741044
TI  - Mechanisms regulating hepatic SR-BI expression and their impact on HDL
      metabolism.
AB  - High-density lipoproteins (HDLs) are major carriers of cholesterol in the
      bloodstream and are critical in regulating cholesterol homeostasis in vivo. The
      first molecularly well-defined and physiologically relevant HDL receptor to be
      characterized was the scavenger receptor class B type I (SR-BI), a cell surface
      glycoprotein most highly expressed in liver and steroidogenic tissues. The HDL
      receptor SR-BI plays a key role in mediating selective HDL cholesterol (HDL-C)
      uptake in the liver, thus controlling cholesterol levels in plasma and the
      transhepatic traffic of this lipid into bile. SR-BI knockout mice exhibit
      increased plasma HDL-C levels and abnormally large HDL particles as well as
      reduced biliary cholesterol levels. Conversely, transgenic mice overexpressing SR
      BI in the liver have markedly reduced plasma HDL levels, accelerated HDL-C
      clearance, increased hepatic selective cholesterol uptake, and raised biliary
      cholesterol content. The regulation of HDL-C metabolism by hepatic SR-BI is
      relevant for cardiovascular health as shown in mouse models where the lack of
      this receptor in the liver induces atherosclerotic lesions, whereas hepatic SR-BI
      overexpression entails a reduction of atherosclerosis. This review summarizes
      some recent progress in understanding the mechanisms that regulate hepatic SR-BI
      expression at transcriptional and post-transcriptional levels, providing
      opportunities for novel approaches that may improve HDL-dependent cholesterol
      homeostasis and lead to better prevention and treatment of atherosclerosis in
      humans.

PMID- 21741043
TI  - Genetic variability within the cholesterol lowering pathway and the effectiveness
      of statins in reducing the risk of MI.
AB  - Genetic variability has been shown to affect statin responsiveness. Participants
      from the Utrecht Cardiovascular Pharmacogenetics (UCP) studies were enrolled from
      a population-based registry of pharmacy records linked to hospital discharge
      records (PHARMO) to investigate tagging SNPs within candidate genes involved in
      the cholesterol lowering pathway for modification of the effectiveness of statins
      in reducing the risk of myocardial infarction (MI). Patients who received a
      prescription for an antihypertensive drug and/or had hypercholesterolemia were
      selected from the PHARMO database. We designed a nested case-control study in
      which cases were hospitalized for MI and controls were not. Patients were
      contacted through their community pharmacies. For this study, only
      hypercholesterolemic participants were selected. Logistic regression analysis was
      used to investigate pharmacogenetic interactions. The Heart and Vascular Health
      Study (HVH) was used to replicate findings from UCP. The study population
      included 668 cases and 1217 controls. We selected 231 SNPs of which 209 SNPs in
      27 genes passed quality control. Ten SNPs in eight genes were found to influence
      the effectiveness of statins in UCP, of which the most significant interaction
      was found with SCARB1 rs4765615. Other genes that reached statistical
      significance (p<0.05) included two SNPs in PCSK9 (rs10888896 and rs505151
      (E670G)), two SNPs in ABCG5 (rs4245786 and rs1864815), LIPC rs16940379, ABCA1
      rs4149264, PPARG rs2972164, LRP1 rs715948, and SOAT1 rs2493121. None of the total
      of 5 SNPs that were available for replication in HVH reached statistical
      significance. In conclusion, ten SNPs were found to modify the effectiveness of
      statins in reducing the risk of MI in the UCP study. Five were also tested in the
      HVH study, but no interactions reached statistical significance.

PMID- 21741045
TI  - Adiponectin: an independent risk factor for coronary heart disease in men in the
      Framingham offspring Study.
AB  - OBJECTIVE: Our aim was to determine whether plasma adiponectin levels were an
      independent predictor of coronary heart disease (CHD) risk. METHODS AND RESULTS:
      Plasma adiponectin levels were measured in 3188 male and female participants from
      cycle 6 of the Framingham offspring Study (mean age: 57 years in both men and
      women; BMI: 28.5 kg/m(2) in men and 27.3 kg/m(2) in women), using a novel fully
      automated assay. Plasma adiponectin levels (median [25th percentile, 75th
      percentile]) were significantly higher in female than in male CHD-free subjects
      (14.8 [10.7,20.5] MUg/ml versus 9.0 [7.0,12.2] MUg/ml, p<0.001). Participants
      were followed for a mean of 7.5 years. After adjustment for age, BMI, smoking
      status, systolic blood pressure, treatment for hypertension, diabetes, use of
      cholesterol-lowering medication, total cholesterol level, high-density
      lipoprotein cholesterol level, and C-reactive protein levels, a higher plasma
      adiponectin level was a significant predictor of lower risk of future CHD events
      (n=117) in men (HR 0.49, p<0.0022). A similar trend was observed in women, but
      was no longer significant after multivariate adjustments. CONCLUSIONS: Our data
      indicate that plasma adiponectin levels are an independent predictor of CHD in
      Caucasian men initially free of CHD.

PMID- 21741046
TI  - Changes in articular cartilage mechanics with meniscectomy: A novel image-based
      modeling approach and comparison to patterns of OA.
AB  - Meniscectomy is a significant risk factor for osteoarthritis, involving altered
      cell synthesis, central fibrillation, and peripheral osteophyte formation. Though
      changes in articular cartilage contact pressure are known, changes in tissue
      level mechanical parameters within articular cartilage are not well understood.
      Recent imaging research has revealed the effects of meniscectomy on the time
      dependent deformation of physiologically loaded articular cartilage. To determine
      tissue-level cartilage mechanics that underlie observed deformation, a novel
      finite element modeling approach using imaging data and a contacting indenter
      boundary condition was developed. The indenter method reproduces observed
      articular surface deformation and avoids assumptions about tangential stretching.
      Comparison of results from an indenter model with a traditional femur-tibia model
      verified the method, giving errors in displacement, solid and fluid stress, and
      strain below 1% (RMS) and 7% (max.) of the absolute maximum of the parameters of
      interest. Indenter finite element models using real joint image data showed
      increased fluid pressure, fluid exudation, loss of fluid load support, and
      increased tensile strains centrally on the tibial condyle after meniscectomy
      patterns corresponding to clinical observations of cartilage matrix damage and
      fibrillation. Peripherally there was decreased consolidation, which corresponds
      to reduced contact and fluid pressure in this analysis. Clinically, these areas
      have exhibited advance of the subchondral growth front, biological destruction of
      the cartilage matrix, cartilage thinning, and eventual replacement of the
      cartilage via endochondral ossification. Characterizing the changes in cartilage
      mechanics with meniscectomy and correspondence with observed tissue-level effects
      may help elucidate the etiology of joint-level degradation seen in
      osteoarthritis.

PMID- 21741047
TI  - Improved g-level calculations for coil planet centrifuges.
AB  - Calculation of the g-level is often used to compare CCC centrifuges, either
      against each other or to allow for comparison with other centrifugal techniques.
      This study shows the limitations of calculating the g-level in the traditional
      way. Traditional g-level calculations produce a constant value which does not
      accurately reflect the dynamics of the coil planet centrifuge. This work has led
      to a new equation which can be used to determine the improved non-dimensional
      values. The new equations describe the fluctuating radial and tangential g-level
      associated with CCC centrifuges and the mean radial g-level value. The latter has
      been found to be significantly different than that determined by the traditional
      equation. This new equation will give a better understanding of forces
      experienced by sample components and allows for more accurate comparison between
      centrifuges. Although the new equation is far better than the traditional
      equation for comparing different types of centrifuges, other factors such as the
      mixing regime may need to be considered to improve the comparison further.

PMID- 21741048
TI  - Low-parachor solvents extraction and thermostated micro-thin-layer chromatography
      separation for fast screening and classification of spirulina from pharmaceutical
      formulations and food samples.
AB  - The goal of this paper is to demonstrate the separation and detection capability
      of eco-friendly micro-TLC technique for the classification of spirulina and
      selected herbs from pharmaceutical and food products. Target compounds were
      extracted using relatively low-parachor liquids. A number of the spirulina
      samples which originated from pharmaceutical formulations and food products, were
      isolated using a simple one step extraction with small volume of methanol,
      acetone or tetrahydrofuran. Herb samples rich in chlorophyll dyes were analyzed
      as reference materials. Quantitative data derived from micro-plates under visible
      light conditions and after iodine staining were explored using chemometrics tools
      including cluster analysis and principal components analysis. Using this method
      we could easily distinguish genuine spirulina and non-spirulina samples as well
      as fresh from expired commercial products and furthermore, we could identify some
      biodegradation peaks appearing on micro-TLC profiles. This methodology can be
      applied as a fast screening or fingerprinting tool for the classification of
      genuine spirulina and herb samples and in particular may be used commercially for
      the rapid quality control screening of products. Furthermore, this approach
      allows low-cost fractionation of target substances including cyanobacteria
      pigments in raw biological or environmental samples for preliminary
      chemotaxonomic investigations. Due to the low consumption of the mobile phase
      (usually less than 1 mL per run), this method can be considered as
      environmentally friendly analytical tool, which may be an alternative for
      fingerprinting protocols based on HPLC machines and simple separation systems
      involving planar micro-fluidic or micro-chip devices.

PMID- 21741049
TI  - Spiral counter-current chromatography of small molecules, peptides and proteins
      using the spiral tubing support rotor.
AB  - An important advance in countercurrent chromatography (CCC) carried out in open
      flow-tubing coils, rotated in planetary centrifuges, is the new design to spread
      out the tubing in spirals. More spacing between the tubing was found to
      significantly increase the stationary phase retention, such that now all types of
      two-phase solvent systems can be used for liquid-liquid partition chromatography
      in the J-type planetary centrifuges. A spiral tubing support (STS) frame with
      circular channels was constructed by laser sintering technology into which FEP
      tubing was placed in 4 spiral loops per layer from the bottom to the top and a
      cover affixed allowing the tubing to connect to flow-tubing of the planetary
      centrifuge. The rotor was mounted and run in a P.C. Inc. type instrument.
      Examples of compounds of molecular weights ranging from <300 to approximately
      15,000 were chromatographed in appropriate two-phase solvent systems to assess
      the capability for separation and purification. A mixture of small molecules
      including aspirin was completely separated in hexane-ethyl acetate-methanol
      water. Synthetic peptides including a very hydrophobic peptide were each purified
      to a very high purity level in a sec-butanol solvent system. In the STS rotor
      high stationary phase retention was possible with the aqueous sec-butanol solvent
      system at a normal flow rate. Finally, the two-phase aqueous polyethylene glycol
      potassium phosphate solvent system was applied to separate a protein from a
      lysate of an Escherichia coli expression system. These experiments demonstrate
      the versatility of spiral CCC using the STS rotor.

PMID- 21741050
TI  - High-resolution separations of protein isoforms with liquid chromatography time
      of-flight mass spectrometry using polymer monolithic capillary columns.
AB  - The separation of intact proteins, including protein isoforms arising from
      various amino-acid modifications, employing a poly(styrene-co-divinylbenzene)
      monolithic capillary column in high-performance liquid chromatography coupled on
      line to a time-of-flight mass spectrometer (MS) is described. Using a 250 mm *
      0.2 mm monolithic capillary column high-sensitivity separations yielding peak
      capacities of >600 were achieved with a 2h linear gradient and formic acid added
      in the mobile phase as ion-pairing agent. The combination of high-resolution
      chromatography with high-accuracy MS allowed to distinguish protein isoforms that
      differ only in their oxidation and biotinylation state allowing the separation
      between structural isoforms. Finally, the potential to separate proteins isoforms
      due to glycosylation is discussed.

PMID- 21741051
TI  - Analysis of oligonucleotides by hydrophilic interaction liquid chromatography
      coupled to negative ion electrospray ionization mass spectrometry.
AB  - Hydrophilic interaction liquid chromatography (HILIC) is here successfully
      coupled to negative-ion electrospray ionization time-of-flight mass spectrometry
      (ESI-TOFMS) for the analysis of synthetic and chemically modified
      oligonucleotides. Separation was performed on a 2.1 mm * 100 mm PEEK ZIC HILIC
      column packed with hydrophilic stationary phase with a permanent zwitterionic
      functional group and a particle size of 3.5 MUm with an average pore diameter of
      200A. A method was developed to separate homogeneous and heterogeneous
      oligonucleotides as well as methylated oligonucleotides using a quaternary
      pumping system containing ammonium acetate and water with an acetonitrile
      gradient. Analyses of oligonucleotides were performed by LC/MS with a detection
      limit of 2.5 picomole (20 mer) with signal to noise ratio (S/N) of 4.12. The
      influence of the eluent composition, type of buffer and its concentration, and
      organic modifier were also evaluated. The HILIC LC/MS method presented in this
      paper used common, 'MS friendly', mobile phases achieving sensitive and selective
      oligonucleotide analysis.

PMID- 21741052
TI  - Paraneoplastic syndrome in haemophagocytic histiocytic sarcoma in a dog.
AB  - A case of metastatic splenic haemophagocytic histiocytic sarcoma (HHS) in a 6
      year-old neutered male flat-coated retriever is described. The main clinical
      findings were hypoalbuminaemia and regenerative anaemia. The diagnosis was based
      on histological features and expression of CD11d by the neoplastic cells. Tumour
      cells were shown to produce interleukin (IL)-6, to phagocytose erythrocytes and
      to take up albumin, as demonstrated by immunohistochemistry and ultrastructural
      examination. Quantitative polymerase chain reaction identified increased IL-6
      gene expression in affected organs. These findings suggest that neoplastic cells
      are responsible for the clinical features of HHS, by removing erythrocytes and
      albumin from the blood and releasing cytokines, such as IL-6.

PMID- 21741053
TI  - Kinetics and pathogenicity of oral infection by equine herpesvirus-9 in mice and
      suckling hamsters.
AB  - The pathogenesis and kinetics of oral infection by equine herpesvirus (EHV)-9
      were studied in mice and hamsters. After oral inoculation of 10(5) plaque-forming
      units (PFU) of virus, 1-week-old suckling hamsters showed varying severity of
      neurological disease from 72 hours post inoculation (hpi) and all of these
      animals had died by 96 hpi. Four-week-old ICR mice inoculated orally with 4 *
      10(4)PFU of virus showed no clinical signs, but they developed erosive and
      ulcerative gastritis from 36 hpi. Varying degrees of encephalitis were seen in
      infected mice and hamsters, and the hamsters also developed myelitis by 96 hpi.
      Immunohistochemistry performed on whole body sections of suckling hamsters
      revealed the kinetics of spread of the virus to the central nervous system. EHV-9
      antigen was detected initially in macrophages of the oral and lingual submucosa.
      At 36 hpi virus antigen was detected in the nerve fibres and pseudounipolar
      neurons of the trigeminal ganglion and at 96 hpi antigen was present in the
      myenteric plexuses of the intestine. Virus antigen was also detected in the
      liver, lungs and heart of affected animals. EHV-9 DNA was detected by polymerase
      chain reaction in the brain, blood and spinal cord of suckling hamsters at 36, 48
      and 96 hpi. These findings show that EHV-9 may spread via the trigeminal nerve
      when mice and hamsters are inoculated orally with virus.

PMID- 21741054
TI  - UW is superior compared with HTK after prolonged preservation of renal grafts.
AB  - BACKGROUND: In recent clinical studies, the efficacy of histidine-tryptophan
      ketoglutarate (HTK) in kidney transplantation was questioned. This study compares
      the efficacy of University of Wisconsin (UW) and HTK solutions on transplantation
      outcome. MATERIALS AND METHODS: Rat kidneys were preserved for different periods
      of cold ischemia (CIT). Heat capacity of the solutions, temperature of the
      grafts, renal function (RF), and histology were assessed before and after
      transplantation, respectively. RESULTS: After prolonged CIT, recipient survival
      was superior in the UW - (100%) compared with the HTK group (10%). In the latter,
      severe tubular necrosis, DNA damage, and renal inflammation were observed,
      reflected by an increased KIM-1, IL6, and P-selectin expression. CIT correlated
      negatively with RF in both groups. RF recovered significantly faster in the UW
      group. LDH-release and ATP depletion after cold storage of tubular cells were
      lower in UW than in HTK. Heat capacity was significantly higher for UW than for
      HTK. Accordingly, renal temperature was lower. CONCLUSIONS: Prolonged
      preservation in UW solution results in a better renal function and less tissue
      damage compared with HTK, possibly due to improved cooling and better cell
      viability of the graft. The use of HTK for renal allografts should therefore be
      reconsidered, particularly when CIT is expected to be long.

PMID- 21741055
TI  - The role of impulse control disorders in Tourette syndrome: an exploratory study.
AB  - INTRODUCTION: Tourette syndrome (TS) is a neurodevelopmental condition
      characterised by the presence of multiple motor tics and one or more phonic tics,
      often associated with co-morbid behavioural problems. Impulse control disorders
      (ICDs) are a set of disorders where patients have significant difficulties in
      controlling their urges to perform rewarding behaviours. ICDs are expected to be
      common in patients with TS, as many problems reported in TS are related to
      difficulties in controlling impulsivity. AIMS: This exploratory study aimed to
      determine the clinical characteristics of ICDs in adult patients with TS, and to
      investigate the relationship between the presence of ICDs and health-related
      quality of life (HR-QOL). METHODS: Thirty-one patients with a diagnosis of TS
      were screened for ICDs using the Minnesota Impulsive Disorders Interview (MIDI).
      HR-QOL was assessed using a generic instrument, the Medical Outcomes Study 36
      Item Short-Form Health Survey (SF-36) and a disease-specific scale, the Gilles de
      la Tourette Syndrome-Quality of Life Scale (GTS-QOL). RESULTS: Twenty-three out
      of 31 participants (74.2%) had at least one ICD. The most common ICDs were
      intermittent explosive disorder (51.6%) and compulsive buying disorder (41.9%).
      The number of ICDs significantly correlated with reduced HR-QOL (p=0.011) as
      measured by the GTS-QOL, but not by the SF-36. CONCLUSIONS: ICDs are common in
      patients with TS. HR-QOL measures specific to this patient population show that
      the presence of co-morbid ICDs results in poorer HR-QOL.

PMID- 21741056
TI  - Prediction of recurrent coarctation by early postoperative blood pressure
      gradient.
AB  - OBJECTIVE: Blood pressure gradients that are noted early after repair of
      coarctation in neonates and infants are often attributed to proximal arch
      hypoplasia. Rapid growth of the hypoplastic proximal arch is usually observed,
      although in some individuals an early gradient predicts the subsequent need for
      reintervention. To define the predictive reliability of blood pressure gradients
      between arms and legs and to identify predictors of arch growth, we undertook a
      retrospective study. METHODS: Between January 2000 and June 2008, 77 infants
      underwent surgical repair of coarctation. Data collected included preoperative
      dimensions of aortic segments. Blood pressure gradients between arms and legs
      determined by cuff were compared intraoperatively and postoperatively, as well as
      2-dimensional echocardiographic dimensions of the aorta between those who did not
      require reintervention for recoarctation (group A) and those who did (group B).
      Receiver operating characteristic curve analysis was applied to evaluate
      discrimination of the systolic gradient in differentiating the 2 groups of
      patients. RESULTS: At surgery, patients' median age was 10 days and weight was
      3.3 kg. There was 1 early death. Median follow-up was 40 months (interquartile
      range, 24-63 months). Recoarctation developed in 11 patients (14.3%), defined as
      a resting blood pressure gradient of greater than 20 mm Hg with a corresponding
      decrease in the diameter of the aorta by 50%. Freedom from recoarctation was 87%
      at 1 year and 85% at 5 years. Multivariable logistic regression analysis
      identified the size of the ascending aorta as a risk factor for recoarctation.
      Blood pressure gradient at the end of surgery was not predictive of
      recoarctation. The ascending aorta and transverse arch showed rapid growth in
      group A, and this was associated with a decrease in blood pressure gradient over
      time. In comparison, the growth of the ascending aorta and arch in group B was
      significantly less than in group A and associated with worsening of gradients.
      Receiver operating characteristic curve analysis revealed that gradients at the
      time of hospital discharge (>13 mm Hg) had excellent discriminative accuracy in
      identifying patients in whom subsequent recoarctation developed. CONCLUSIONS:
      Small size of the ascending aorta is a risk factor for recoarctation. Limb
      gradient in the operating room at completion of surgery is not a reliable tool to
      assess repair of coarctation, although the gradient at the time of hospital
      discharge can be used to accurately predict recoarctation. Rapid growth of both
      the ascending and the transverse aorta is frequently observed and associated with
      improvement in gradients over time.

PMID- 21741057
TI  - Long-term metreleptin treatment increases bone mineral density and content at the
      lumbar spine of lean hypoleptinemic women.
AB  - Strenuously exercising young women with hypothalamic amenorrhea are
      hypoleptinemic and have low bone mineral density (BMD) and content (BMC), which
      predispose them to increased fracture risk. Short-term leptin replacement in
      these women corrects many neuroendocrine abnormalities and increases circulating
      levels of bone formation markers. Whether treatment with recombinant methionyl
      human leptin (metreleptin) for a long period improves BMD and BMC remains
      unknown. We studied 20 strenuously exercising young women with hypoleptinemia
      (leptin concentration <5 ng/mL) and hypothalamic amenorrhea of at least 6 months'
      duration. Eleven were randomized to metreleptin (initial dose, 0.08 mg/[kg.d] for
      3 months; altered thereafter to 0.12 mg/kg for lack of efficacy or 0.04 mg/[kg d]
      for more than 5% weight loss) and 9 were randomized to placebo for 9 months.
      After a 3-month washout period, subjects were reexamined at the 1-year time
      point. Six subjects elected to continue on open-label metreleptin treatment for
      another 12 months. Two subjects dropped out after 18 months, and 4 completed the
      entire 2-year study. The BMD and BMC of the total body, lumbar spine (L1-L4),
      hip, and radius were assessed by using dual-energy x-ray absorptiometry at
      baseline and at 3, 6, 9, 12, 18, and 24 months of treatment. Metabolic and
      hormonal parameters and bone markers were measured in blood and urine.
      Metreleptin significantly increased BMC (P = .034) and tended to increase BMD (P
      = .069) at the lumbar spine at 9 months in the entire study group (intention-to
      treat analysis). In subjects who completed the entire 2-year study (n = 4),
      metreleptin significantly increased BMD (P = .024) and BMC (P = .049) at the
      lumbar spine by 4% to 6%. Changes were not significant at the whole body, hip,
      and radius. Changes in hormonal and metabolic parameters and bone markers were
      moderate during the first year of treatment, but metreleptin further increased
      insulin-like growth factor 1 and decreased cortisol and cross-linked C-terminal
      telopeptide of type 1 collagen concentrations in serum during the second year of
      treatment (P < .05). The incremental area under the estradiol concentration curve
      over the 2-year course of the study correlated positively with the corresponding
      increase in lumbar spine BMD (rho = 0.42, P = .039). Long-term metreleptin
      administration in strenuously exercising young women with hypothalamic amenorrhea
      and hypoleptinemia increases lumbar spine BMD and BMC and alters bone remodeling
      milieu to favor bone accretion. Results from this pilot study should be confirmed
      by future, larger clinical trials and need to be extended by studying bone
      microarchitecture and fracture risk.

PMID- 21741058
TI  - Rosiglitazone increases fatty acid Delta9-desaturation and decreases elongase
      activity index in human skeletal muscle in vivo.
AB  - The ratio of unsaturated to saturated long-chain fatty acids (LC-FAs) in skeletal
      muscle has been associated with insulin resistance. Some animal data suggest a
      modulatory effect of peroxisome proliferator receptor gamma (PPARgamma)
      stimulation on stearoyl-CoA desaturase 1 (SCD1) and LC-FA composition in skeletal
      muscle, but human data are rare. We here investigate whether treatment with a
      PPARgamma agonist affects myocellular SCD1 expression and modulates the
      intramyocellular fatty acid profile in individuals with impaired glucose
      tolerance. Muscle biopsies and hyperinsulinemic-euglycemic clamps were performed
      in 7 men before and after 8 weeks of rosiglitazone treatment. Intramyocellular
      saturated, monounsaturated, and polyunsaturated intramuscular fatty acid profiles
      were measured by gas chromatography. Effects on SCD1 messenger RNA expression
      were analyzed in C2C12 cells and in human biopsies before and after rosiglitazone
      treatment. As expected, treatment with the PPARgamma activator rosiglitazone
      improved insulin sensitivity in humans. Myocellular SCD1 messenger RNA expression
      was increased in human biopsies and C2C12 cells. Although the total content of
      myocellular LC-FA was unchanged, a relative shift from saturated LC-FAs to
      unsaturated LC-FAs was observed in human biopsies. Particularly, the amount of
      stearate was reduced, whereas the amounts of palmitoleate as well as oleate and
      vaccenate were increased, after rosiglitazone therapy. These changes resulted in
      an increased fatty acid Delta9-desaturation index (16:1/16:0 and 18:1/18:0) in
      skeletal muscle and a decreased elongase activity index (18:0/16:0). The
      PPARgamma associated phenotypes may be partially explained by an increased Delta9
      desaturation and a decreased elongase activity of skeletal muscle.

PMID- 21741059
TI  - Retinol-binding protein 4 is not associated with insulin resistance in pregnancy.
AB  - Retinol-binding protein 4 (RBP4) is an adipokine proposed to be specifically
      associated with insulin resistance (IR). We examined whether serum levels of RBP4
      were associated with IR in pregnancy. One hundred seventy-two women with
      gestational diabetes mellitus (GDM) and 361 pregnant Thai women who did not have
      GDM but had a positive 50-g glucose challenge test result (plasma glucose level
      was >=7.2 mmol/L after 1 hour) were enrolled. We measured fasting serum levels of
      RBP4 and assessed IR at a 100-g oral glucose tolerance test. We found a higher
      degree of IR in the GDM group compared with the non-GDM group, but serum RBP4
      levels between the 2 groups were not different. Retinol-binding protein 4 levels
      were associated with serum triglyceride levels but were not associated with the
      degree of IR assessed by homeostasis model assessment or quantitative insulin
      sensitivity check index. Our results suggest that serum RBP4 levels in pregnancy
      are not associated with IR.

PMID- 21741060
TI  - Circulating levels of insulin-like growth factor binding protein-1 in relation to
      insulin resistance, type 2 diabetes mellitus, and metabolic syndrome (Chennai
      Urban Rural Epidemiology Study 118).
AB  - The objective was to assess the association of insulin-like growth factor binding
      protein-1 (IGFBP-1) with insulin resistance (IR), type 2 diabetes mellitus
      (T2DM), and metabolic syndrome (MS) in Asian Indians. Fifty subjects with normal
      glucose tolerance (NGT) and 50 with T2DM were randomly selected from the Chennai
      Urban Rural Epidemiology Study. Insulin-like growth factor binding protein-1 was
      measured by sandwich enzyme-linked immunosorbent assay. Serum insulin was
      estimated using Dako (Glostrup, Denmark) kits. Insulin resistance was calculated
      using the homeostasis model assessment. Subjects with T2DM had significantly
      decreased levels of IGFBP-1 (21.7 +/- 3.5 ng/mL) compared with NGT subjects (34.4
      +/- 7.6 ng/mL, P < .001). The IGFBP-1 was significantly lower in NGT subjects
      with IR as measured by the homeostasis model assessment (25.5 +/- 6.5 ng/mL)
      compared with NGT subjects without IR (40.7 +/- 9.5 ng/mL, P < .001). On
      regression analysis, IR showed a significant association with IGFBP-1 even after
      adjusting for age, sex, body mass index, and glycated hemoglobin (beta = -3.714,
      P < .001). Type 2 diabetes mellitus was significantly associated with IGFBP-1
      even after adjusting for age, sex, and body mass index (beta = -12.798, P <
      .001). The IGFBP-1 levels decreased with increasing number of metabolic
      abnormalities (P for trend < .001). Logistic regression analysis showed that
      IGFBP-1 had a strong negative association with MS even after adjusting for age
      and sex (odds ratio, 0.942; 95% confidence interval, 0.914-0.971; P < .001).
      Among Asian Indians, lower levels of circulating IGFBP-1 are seen in subjects
      with IR, T2DM, and MS.

PMID- 21741061
TI  - The doctor of nursing practice: a national workforce perspective.

PMID- 21741062
TI  - Mixed messages: hospital practices that serve as disincentives for associate
      degree-prepared nurses to return to school.
AB  - Nearly 80% of associate's degree-prepared nurses do not return to school for a
      more advanced degree in nursing, which is an issue of concern to many nursing
      leaders. This interpretive phenomenological study investigates what influences
      associate's degree-prepared nurses to refrain from continuing their professional
      education and obtain a baccalaureate or higher-level degree. Although these
      nurses generally wished they had a higher degree, they did not feel pursuing one
      was necessary. They did not perceive that their standard of patient care would
      change with further professional training involved in obtaining a higher
      educational degree. Furthermore, they did not perceive any distinctions in
      professional ability between themselves and colleagues with more advanced nursing
      degrees. The culture of service health care organizations in which associate's
      degree-prepared nurses are employed, as well as other factors, are likely
      directly responsible for the practicing nurses' lack of appreciation for the
      relevancy and rewards of returning to school.

PMID- 21741063
TI  - Sedimentation of helminth eggs in water.
AB  - Helminth parasite eggs in low quality water represent health risks when used for
      irrigation of crops. The settling velocities of helminth eggs (Ascaris suum,
      Trichuris suis, and Oesophagostomum spp.) and wastewater particles were
      experimentally determined in tap water and in wastewater using Owen tubes. The
      settling velocities of eggs in tap water was compared with theoretical settling
      velocities calculated by Stoke's law using measurements of size and density of
      eggs as well as density and viscosity of tap water. The mean settling velocity in
      tap water of 0.0612 mm s(-1) found for A. suum eggs was significantly lower than
      the corresponding values of 0.1487 mm s(-1) for T. suis and 0.1262 mm s(-1) for
      Oesophagostomum spp. eggs. For T. suis and Oesophagostomum spp. eggs the
      theoretical settling velocities were comparable with the observed velocities in
      the Owen tubes, while it was three times higher for A. suum eggs. In wastewater,
      the mean settling velocity for A. suum eggs (0.1582 mm s(-1)) was found to be
      different from T. suis (0.0870 mm s(-1)), Oesophagostomum spp. (0.1051 mm s(-1)),
      and wastewater particles (0.0474 mm s(-1)). This strongly indicates that in low
      quality water the eggs are incorporated into particle flocs with different
      settling velocities and that the settling velocity of eggs and particles is
      closely associated. Our results document that there is a need to differentiate
      the sedimentation of different types of helminth eggs when assessing the quality
      of low quality water, e.g. for irrigation usage. The results can also be used to
      improve existing models for helminth egg removal.

PMID- 21741064
TI  - Occurrence and treatment of wastewater-derived organic nitrogen.
AB  - Dissolved organic nitrogen (DON) derived from wastewater effluent can participate
      in reactions that lead to formation of nitrogenous chlorination by-products,
      membrane fouling, eutrophication, and nitrification issues, so management of DON
      is important for both wastewater reuse applications and nutrient-sensitive
      watersheds that receive discharges from treated wastewater. This study documents
      DON occurrence in full-scale water/wastewater (W/WW) treatment plant effluents
      and assesses the removal of wastewater-derived DON by several processes
      (biodegradation, coagulation, softening, and powdered activated carbon [PAC]
      adsorption) used for advanced treatment in wastewater reuse applications. After
      varying levels of wastewater treatment, the dominant aqueous nitrogenous species
      shifts from ammonia to nitrate after aerobic processes and nitrate to DON in
      tertiary treatment effluents. The fraction of DON in total dissolved nitrogen
      (TDN) accounts for at most 52% in tertiary treated effluents (median=13%) and 54%
      in surface waters impacted by upstream wastewater discharges (median=31%). The 5
      day biodegradability/bioavailability of DON (39%) was higher, on average, than
      that of dissolved organic carbon (DOC, 26%); however, upon chlorination, the DON
      removal (3%) decreased significantly. Alum coagulation (with >=8 mg/L alum per
      mg/L DOC) and lime softening (with pH 11.3-11.5) removed<25% of DON and DOC
      without selectivity. PAC adsorption preferentially removed more DOC than DON by
      10% on average. The results provided herein hence shed light on approaches for
      reducing organic nitrogen content in treated wastewater.

PMID- 21741065
TI  - Cellular damages in the Allium cepa test system, caused by BTEX mixture prior and
      after biodegradation process.
AB  - Petroleum and derivatives have been considered one of the main environmental
      contaminants. Among petroleum derivatives, the volatile organic compounds
      benzene, toluene, ethylbenzene and xylene (BTEX) represent a major concern due to
      their toxicity and easy accumulation in groundwater. Biodegradation methods seem
      to be suitable tools for the clean-up of BTEX contaminants from groundwater.
      Genotoxic and mutagenic potential of BTEX prior and after biodegradation process
      was evaluated through analyses of chromosomal aberrations and MN test in
      meristematic and F(1) root cells using the Allium cepa test system. Seeds of A.
      cepa were germinated into five concentrations of BTEX, non-biodegraded and
      biodegraded, in ultra-pure water (negative control), in MMS 4*10(-4)M (positive
      control) and in culture medium used in the biodegradation (blank biodegradation
      control). Results showed a significant frequency of both chromosomal and nuclear
      aberrations. The micronucleus (MN) frequency in meristematic cells was
      significant for most of tested samples. However, MN was not present in
      significant levels in the F(1) cells, suggesting that there was no permanent
      damage for the meristematic cell. The BTEX effects were significantly reduced in
      the biodegraded samples when compared to the respective non-biodegraded
      concentrations. Therefore, in this study, the biodegradation process showed to be
      a reliable and effective alternative to treat BTEX-contaminated waters. Based on
      our results and available data, the BTEX toxicity could also be related to a
      synergistic effect of its compounds.

PMID- 21741066
TI  - Assessing the transformation of chlorinated ethenes in aquifers with limited
      potential for natural attenuation: added values of compound-specific carbon
      isotope analysis and groundwater dating.
AB  - The evaluation of biotransformation of chlorinated ethenes (CEs) in contaminated
      aquifers is challenging when variable redox conditions and groundwater flow
      regime are limiting factors. By using compound-specific stable carbon isotope
      analysis (C-CSIA) and 3H-3He based groundwater dating, we assessed three CE
      contaminated field sites that differed in groundwater flow velocities, redox
      conditions, and level of contamination. CE isotopic signatures and carbon
      isotopic mass balances were applied to quantify CE transformation, whereas
      groundwater dating allowed determining degradation timescales and assessing
      hydrodynamic regimes. The combination of these techniques enabled at all field
      sites to indicate zones within the aquifers where CE dechlorination preferably
      occurred, sometimes even to metabolites of no toxic concern. However, the natural
      transformation processes were insufficient to mitigate the entire CE
      contamination at the studied sites. Such situations of limited transformation are
      worldwide far more common than sites where optimal natural (mainly redox)
      conditions are enabling complete CEs degradation. Despite such constraints for
      natural transformation, this study showed that even under non-favorable
      biogeochemical CEs degradation, the combination of CSIA and groundwater dating
      provide valuable information to the understanding of the fate of the CEs, thus,
      being an important contribution in the definition of efficient remediation
      measures at any given biogeochemical conditions.

PMID- 21741067
TI  - Analysis of pesticide residues using the Quick Easy Cheap Effective Rugged and
      Safe (QuEChERS) pesticide multiresidue method in traditional Chinese medicine by
      gas chromatography with electron capture detection.
AB  - The Quick Easy Cheap Effective Rugged and Safe multiresidue method (QuEChERS) has
      been validated for the extraction of 15 organochlorine pesticides (OCPs) in
      completely different matrices of traditional Chinese medicine (TCM). The method
      employed a rapid, simple and cost-effective procedure. The spiking levels for the
      recovery experiments were 0.1, 0.5 and 2.0 mg kg(-1). Mean recoveries mostly
      ranged between 76.0% and 114.0% (96.0% on average), and relative standard
      deviations (RSD) were generally below 10% (4.72% on average). Based on these
      results, the methodology has been proven to be highly efficient and robust and
      thus suitable for monitoring the MRL compliance of a wide range of commodity. The
      contamination status of 15 OCPs on 80 different TCMs marketed in China, and a
      total of 400 samples were also performed using a previously validated method. 15
      OCPs were benzene hexachloride (BHC, including alpha-BHC, beta-BHC, gamma-BHC,
      delta-BHC), hexachlorobenzene, heptachlor, heptachlor epoxide, aldrin, p, p'-DDE,
      p, p'-DDD, o, p'-DDT, p, p'-DDT, mirex, endrin, dieldrin. This study indicates
      that the proposed method is useful for analyzing OCPs in TCM.

PMID- 21741068
TI  - Determination of PCBs, PCDDs and PCDFs in insulating oil samples from stored
      Chinese electrical capacitors by HRGC/HRMS.
AB  - Homologue and congener profiles of polychlorinated biphenyls (PCBs),
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) in commercial PCBs formulations are key information for the source
      identification of PCBs contamination as well as for the risk assessment caused by
      potential exposure. The isotope dilution technology in combination with high
      resolution gas chromatography-high resolution mass spectrometry (HRGC/HRMS) has
      made the accurate determination of such profiles possible. So far, various
      commercial PCB formulations except Chinese products have been successfully
      determined. Two PCBs containing insulating oil samples from stored Chinese
      electrical capacitors have been determined with the same methodology for
      comparability. The total concentration PCBs in two oil samples were 790,000 MUg
      g(-1) and 720,000 MUg g(-1), respectively. TriCBs, TetraCBs, and DiCBs were found
      to be most abundant. Concentration of dioxins contamination in two samples is 650
      670 ng TEQ g(-1), of which 69-71ngTEQg(-1) from PCDD/Fs with the predominant
      congeners of 1,2,7,8-TeCDF; 2,3,7,8-TeCDF; 2,3,4,7,8-PeCDF and 1,2,3,7,8-PeCDF.
      The contributions of DL-PCBs in total TEQ in both samples were more than 85%. The
      dioxin-like toxicity in insulating oils contained in electrical capacitors could
      be considered receive attention as an important dioxins source if such wastes are
      not managed in an environmentally sound manner.

PMID- 21741069
TI  - Contamination and bioaccumulation of benzotriazole ultraviolet stabilizers in
      fish from Manila Bay, the Philippines using an ultra-fast liquid chromatography
      tandem mass spectrometry.
AB  - Benzotriazole ultraviolet stabilizers (BUVSs) used in plastic products, building
      materials and personal hygiene products were analyzed in fishes collected from
      Manila Bay, the Philippines. BUVSs were detected at ng g-1 level in all the fish
      samples, indicating their ubiquitous contamination in coastal waters. Among the
      targeted eight BUVSs, UV-328 was predominantly found with a mean concentration of
      34.2 ng g-1 lipid weight, implying large scale production and use of this
      compound in the Philippines. High concentrations of ?BUVSs were found in bumpnose
      trevally (Carangoides hedlandensis), bluetail mullet (adult) (Valamugil
      buchanani), common ponyfish (Leiognathus equulus) and coral grouper (adult)
      (Epinephelus corallicola) indicating their active uptake and/or lower metabolic
      capacity to eliminate BUVSs. Among BUVSs, UV-P showed significant positive
      relationship (p<0.05) between concentration and fish length (r=0.29) and fish
      weight (r=0.31). Levels of UV-P in demersal species had positive correlation with
      delta15N, indicating that possibile sink of UV-P is bottom sediment in the bay,
      and ultimately accumulate through benthic food web rather than pelagic food web.
      To our knowledge, this is the first study on BUVSs distribution in fish from
      developing countries.

PMID- 21741070
TI  - Solanum nigrum L. weed plants as a remediation tool for metalaxyl-polluted
      effluents and soils.
AB  - In this work, the phytoremediation potential of metalaxyl, a commonly used
      persistent, mobile and leachy fungicide, by Solanum nigrum L. plants was studied.
      The study revealed that this plant species can be used as an excellent metalaxyl
      phytoremediation tool, thus providing a cost effective and environmentally
      friendly clean technology for the decontamination of sites and effluents. As it
      can be sowed directly in the remediation site, is able to complete its life cycle
      without suffering major stress. Because it accumulates high amounts of the
      fungicide in the aboveground tissues, enables its concentration and proper
      disposal by cutting off the corresponding plant part. The study also suggests
      that the tolerance to metalaxyl is due to a suitable antioxidant response
      comprising proline accumulation and guaiacol peroxidase and glutathione-S
      transferase enhanced activities, that reduce oxidative damage to the plant
      organs.

PMID- 21741071
TI  - Hydroxytyrosol, the phenolic compound of olive oil protects human PBMC against
      oxidative stress and DNA damage mediated by 2,3,7,8-TCDD.
AB  - The protective effect of hydroxytyrosol (HT), a strong antioxidant compound from
      extra virgin olive oil, against TCDD induced toxicity was investigated in human
      peripheral blood mononuclear cells (PBMC). PBMC (1 * 10(6)cellsmL(-1)) were
      divided into four groups and were incubated in a CO(2) incubator (5% CO(2)) for
      12h with vehicle, TCDD (10 nM), TCDD+HT (10 nM+100 MUM) and HT alone (100 MUM)
      respectively. To clarify the role of HT against TCDD induced cytotoxicity,
      oxidative stress and the levels of antioxidant enzymes were assessed. Incubation
      of PBMC with TCDD significantly decreased cell viability, catalase (CAT) and
      glutathione peroxidase (GPx) and increased the levels of superoxide dismutase
      (SOD), glutathione reductase (GR) and oxidative stress markers such as lipid
      peroxidation products (LPO), protein carbonyl content (PCC) and reactive oxygen
      species (ROS). Whereas, HT had an effective antioxidant property as observed by
      the increased cell viability, normalization of antioxidant enzymes and decreased
      levels of LPO, PCC and ROS in PBMC co-treated with HT and TCDD. Apoptosis
      detection and comet assay results shows that HT, by acting as an antioxidant,
      prevents the damage to DNA induced by TCDD. In addition light microscopic and
      histopathological observations revealed that the cells are apoptotic and
      degenerated during TCDD treatment, whereas cells showed intact morphology during
      co-treatment with HT. On the whole, the results reveal that HT exerts a promising
      antioxidant potential in protecting the PBMC against TCDD induced oxidative
      stress, which might be due to the presence of catechol moiety in its structure.

PMID- 21741072
TI  - Raw material selectivity in Late Pliocene Oldowan sites in the Makaamitalu Basin,
      Hadar, Ethiopia.
AB  - We report the results of an analysis of raw material selection patterns in the
      assemblages from two Late Pliocene in situ archaeological localities in the
      Makaamitalu Basin (Hadar, Ethiopia). While the same local conglomerate was used
      as a raw material source for both archaeological occurrences, different selection
      criteria are identified. At A.L. 894, selection for quality is subtle and the
      clearest selection is against non-homogeneous raw materials. In the A.L. 666
      assemblage, higher-quality raw materials were selected and some rare raw
      materials reached the locality from unknown sources. A comparison between the
      Makaamitalu and other Oldowan assemblages reveals an overall shift toward higher
      complexity of both selectivity and transport behaviors from ca. 2.0 Ma onward,
      contrasting a typo-technological conservatism that pertains until ~1.6 Ma. It is
      hypothesized that an increase in complexity of behaviors related to raw material
      selection and acquisition involved changes in the intensity and fidelity of
      technological knowledge transmission.

PMID- 21741073
TI  - Plant tolerance to diesel minimizes its impact on soil microbial characteristics
      during rhizoremediation of diesel-contaminated soils.
AB  - Soil contamination due to petroleum-derived products is an important
      environmental problem. We assessed the impacts of diesel oil on plants (Trifolium
      repens and Lolium perenne) and soil microbial community characteristics within
      the context of the rhizoremediation of contaminated soils. For this purpose, a
      diesel fuel spill on a grassland soil was simulated under pot conditions at a
      dose of 12,000 mg diesel kg(-1) DW soil. Thirty days after diesel addition, T.
      repens (white clover) and L. perenne (perennial ryegrass) were sown in the pots
      and grown under greenhouse conditions (temperature 25/18  degrees C day/night,
      relative humidity 60/80% day/night and a photosynthetic photon flux density of
      400 MUmol photon m(-2) s(-1)) for 5 months. A parallel set of unplanted pots was
      also included. Concentrations of n-alkanes in soil were determined as an
      indicator of diesel degradation. Seedling germination, plant growth, maximal
      photochemical efficiency of photosystem II (F(v)/F(m)), pigment composition and
      lipophylic antioxidant content were determined to assess the impacts of diesel on
      the studied plants. Soil microbial community characteristics, such as enzyme and
      community-level physiological profiles, were also determined and used to
      calculate the soil quality index (SQI). The presence of plants had a stimulatory
      effect on soil microbial activity. L. perenne was far more tolerant to diesel
      contamination than T. repens. Diesel contamination affected soil microbial
      characteristics, although its impact was less pronounced in the rhizosphere of L.
      perenne. Rhizoremediation with T. repens and L. perenne resulted in a similar
      reduction of total n-alkanes concentration. However, values of the soil microbial
      parameters and the SQI showed that the more tolerant species (L. perenne) was
      able to better maintain its rhizosphere characteristics when growing in diesel
      contaminated soil, suggesting a better soil health. We concluded that plant
      tolerance is of crucial importance for the recovery of soil health during
      rhizoremediation of contaminated soils.

PMID- 21741074
TI  - Harmonization and external quality assessment of antithrombin activity assays.
AB  - In the framework of a Dutch project named "Calibration 2000" harmonization of
      antithrombin activity assays was studied. The commutability of potential
      calibrators for antithrombin was assessed by means of a twin-study design, which
      is a multicentre, split-patient sample, between-field-methods protocol. The twin
      study consisted of simultaneous analysis of fresh-frozen patient plasmas and
      three potential calibrators for antithrombin by 30 Dutch laboratories forming 15
      couples. The state-of-the-art intralaboratory standard deviation (SD(SA)) was
      used to assess the commutability of the potential calibrators. The regression
      line residuals for the potential calibrators were normalized by expressing them
      as multiples of SD(SA). All residuals of the potential calibrators were within
      the 3*SD(SA) limit. One potential calibrator was used in an attempt to harmonize
      antithrombin assay results in a Dutch field study. The interlaboratory
      coefficient of variation (CV) of the antithrombin results for three test samples
      could be reduced from 6.9 - 13.2% (before harmonization) to 5.6 - 9.8% using the
      common calibrator. CONCLUSION: The potential calibrators were commutable. Limited
      harmonization was achieved by using a common calibrator for all participants.

PMID- 21741075
TI  - Combination oral antiplatelet therapy may increase the risk of hemorrhagic
      complications in patients with acute ischemic stroke caused by large artery
      disease.
AB  - INTRODUCTION: The association between the frequency or severity of bleeding
      complications and combination antiplatelet therapy for acute stroke treatment is
      not understood in detail. This retrospective study investigated whether
      combination oral antiplatelet therapy for cases with acute ischemic stroke due to
      large artery disease increased the incidence of hemorrhagic complications.
      MATERIALS AND METHODS: We reviewed 1335 consecutive patients who were admitted to
      our department within 7 days of the onset of an ischemic stroke or transient
      ischemic attack between April 2005 and November 2009. We enrolled 167 patients
      with >50% stenosis or occlusion in culprit major vessels and who were
      administered oral antiplatelet agents within 48 hours of admission. Hemorrhagic
      complications were classified according to the bleeding severity index. We
      studied the association between the incidence and severity of hemorrhagic
      complications during hospitalization and the clinical characteristics, including
      antiplatelet therapy. RESULTS: Fifty-nine and 108 patients were treated with only
      1 antiplatelet agent and combination antiplatelet agents, respectively. Fourteen
      patients developed bleeds (3 major and 11 minor), and all of the major bleeds
      occurred in those given combination agents. The proportion of patients receiving
      combination agents was significantly higher in those with significant bleeds.
      Multivariate logistic regression analysis revealed that being older and receiving
      combination agents were independent predictors for significant bleeds during
      hospitalization. CONCLUSIONS: Despite the retrospective nature of this study, our
      findings suggest that the incidence of hemorrhagic complications increases in
      patients with acute ischemic stroke treated with combination antiplatelet agents.

PMID- 21741076
TI  - Application, tolerance and safety of fondaparinux therapy in a German hospital: a
      prospective single-centre experience.
AB  - INTRODUCTION: The pentasaccharide fondaparinux is widely approved for prophylaxis
      and treatment of thromboembolic diseases and therapy of acute coronary syndrome.
      It is also used off-label in patients with acute, suspected or antecedent heparin
      induced thrombocytopenia (HIT). The aim of this prospective observational cohort
      study was to document fondaparinux' prescription practice, tolerance and therapy
      safety in a representative mixed German single-centre patient cohort. PATIENTS
      AND METHODS: Between 09/2008 - 04/2009, 231 consecutive patients treated with
      fondaparinux were enrolled. Medical data were obtained from patient's records.
      The patients were clinically screened for thrombosis (Wells score), sequelae of
      HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to
      further assessment (i.e. sonography, HIT-diagnostics), if necessary. The
      mortality rate was assessed 30 days after therapy start. RESULTS: Overall,
      153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231
      patients a successive prophylactic/therapeutic indication. In 11/231 patients
      fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a
      previous cutaneous delayed-type hypersensitivity to heparins. Other indications
      were rare. Three new/progressive thromboses were detected. No cases of HIT, major
      bleedings, or fatalities occurred. CONCLUSIONS: Fondaparinux was well tolerated
      and was safe in prophylaxis and therapy; prescriptions mostly followed the
      current approval guidelines and were rarely related to HIT-associated indications
      (<5% of prescriptions), which is in contrast to previous study results in the
      U.S. (>94% of prescriptions were HIT-associated). A trend towards an
      individualised fondaparinux use based on the compound's inherent properties and
      the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin
      allergy, was observed.

PMID- 21741077
TI  - High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas.
AB  - OBJECTIVE: To investigate the prognostic role of Beclin 1 in endometrial
      adenocarcinomas of the endometrioid cell type. Beclin 1 is a known tumor
      suppressor gene, but its function may be altered under conditions of an
      accelerated autophagic activity, which provides additional energy to
      proliferating cells by recycling defective organelles and long-lived cytoplasmic
      proteins. MATERIALS AND METHODS: One hundred and fifty-five endometrioid
      adenocarcinomas were investigated for their autophagic activity using the
      monoclonal antibody Beclin 1 and an automated immunohistochemical technique. The
      extent of Beclin 1 expression was evaluated on a three-tier scale as follows: low
      (<10% positive tumor cells), intermediate (between 10% and 50% positive tumor
      cells), and high (>50% positive tumor cells). The results were correlated with
      the degree of tumor differentiation, the depth of myometrial invasion and the
      overall 5-year survival. In addition, the endometrial tumors were immunostained
      with the hypoxia inducible factor 1alpha (HIF1alpha) and their expression was
      related to Beclin 1. RESULTS: A high Beclin 1 reactivity occurred in 18.1% of
      endometrial adenocarcinomas studied and was associated with high tumor grade,
      high myometrial invasion and a poor 5-year survival. It was also correlated
      positively with HIF1alpha. Of the remaining adenocarcinomas 29.7% were of
      intermediate Beclin 1 reactivity and 52.2% of low, but correlations with
      prognostic factors were insignificant. CONCLUSION: An increased Beclin 1
      expression is connected with the most aggressive endometrioid adenocarcinomas,
      probably as a result of its strong association with tumor hypoxia.

PMID- 21741078
TI  - Racial disparities in histopathologic characteristics of uterine cancer are
      present in older, not younger blacks in an equal-access environment.
AB  - OBJECTIVE: We sought to determine whether racial disparities in tumor
      characteristics among uterine cancer patients persisted, and varied by age, in an
      equal-access healthcare population. METHODS: The distributions of tumor
      histology, stage and grade by race were compared for uterine cancers diagnosed
      from 1990 to 2003 using data from the U.S. Department of Defense's Automated
      Central Tumor Registry. Comparisons were conducted overall and stratified by age
      (<50, >=50) using the Chi-square test. RESULTS: Of 2582 uterine tumors
      identified, 2057 (79.7%) were diagnosed among White women and 183 (7.1%) among
      Black women. Among all women analyzed, Blacks were more likely than Whites to
      present with non-endometrioid tumors (47.7% vs 23.5%, p<0.01), non-localized
      tumors (31.8% vs 24.5%, p=0.02), and poorly differentiated tumors (20.5% vs
      15.0%, p<0.01). Among women 50 years and older, similar significant racial
      disparities were observed. However, no significant racial differences were
      observed among young patients. When comparisons were restricted to endometrioid
      histology adenocarcinomas, trends in age-specific disparities for older women
      were observed. CONCLUSIONS: Our study suggests that racial disparities in uterine
      cancers persist between Blacks and Whites in an equal-access population. Blacks
      endure higher stage and grade tumors, and more aggressive histologies. This
      disparity in clinicopathologic factors is confined to women older than 50 years.
      Multiple factors such as racial variation in age-related health
      knowledge/behavior and estrogen metabolism may be related to the racial
      disparity.

PMID- 21741079
TI  - Laparoscopic-assisted cytoreduction for primary advanced ovarian cancer: success,
      morbidity and survival.
AB  - OBJECTIVE: The purpose of this paper is to evaluate laparoscopic-assisted
      cytoreduction for primary advanced ovarian cancer: feasibility, morbidity,
      response to chemotherapy and survival. METHODS: All patients with presumed stage
      3/4 primary ovarian cancer underwent attempted laparoscopic cytoreduction. All
      patients had CT evidence of omental metastasis and ascites. A five port (5-mm)
      transperitoneal approach was used. A bilateral salpingo-oophorectomy,
      supracervical hysterectomy and omentectomy were performed with the PlasmaKinetic
      (PK) cutting forceps. A laparoscopic 5-mm Argon-Beam Coagulator was used to
      coagulate tumor in the pelvis, abdominal peritoneum, intestinal mesentery, and
      diaphragm. RESULTS: Twenty-three cases (92%) were successfully cytoreduced
      laparoscopically without conversion to laparotomy. Median operative time was 2.3h
      and median blood loss was 340 cc. All tumors were debulked to less than 2 cm and
      36% had no residual disease. Median length of stay was 1 day. Median VAS pain
      score was 4-discomforting. Six patients (24%) had post-operative complications,
      none grades 3-4. Median overall survival is 3.5 years. CONCLUSION: Laparoscopic
      assisted cytoreduction for primary advanced ovarian cancer was successful,
      resulting in minimal morbidity, and acceptable survival.

PMID- 21741080
TI  - Toll-like receptor 9, transmembrane activator and calcium-modulating cyclophilin
      ligand interactor, and CD40 synergize in causing B-cell activation.
AB  - BACKGROUND: B cells receive activating signals from T cells through CD40, from
      microbial DNA through Toll-like receptor (TLR) 9, and from dendritic cells
      through transmembrane activator and calcium-modulating cyclophilin ligand
      interactor (TACI). TLR9 and CD40 ligation augment TACI-driven B-cell activation,
      but only the mechanism of synergy between CD40 and TACI has been explored.
      Synergy between CD40 and TLR9 in B-cell activation is controversial. OBJECTIVE:
      We sought to examine the mechanisms by which TLR9 modulates CD40- and TACI
      mediated activation of B cells and to determine whether all 3 receptors synergize
      to activate B cells. METHODS: Naive murine B cells and human PBMCs were
      stimulated with combinations of anti-CD40, CpG, and a proliferation inducing
      ligand in the presence of IL-4. Proliferation was measured by means of tritiated
      thymidine incorporation. Immunoglobulin production was measured by means of
      ELISA. Class-switch recombination (CSR) was examined by measuring mRNA for
      germline transcripts, activation-induced cytidine deaminase (AICDA), and mature
      immunoglobulin transcripts. Plasma cell differentiation was examined by using
      syndecan-1/CD138 staining and mRNA expression of B lymphocyte-induced maturation
      protein 1 (Blimp-1). RESULTS: TLR9 synergized with CD40 and TACI in driving CSR
      and inducing IgG(1) and IgE secretion by naive murine B cells and synergized with
      TACI in driving B-cell proliferation and plasma cell differentiation. All 3
      receptors synergized together in driving murine B-cell proliferation, CSR, plasma
      cell differentiation, and IgG(1) and IgE secretion. TLR9 synergized with CD40 and
      TACI in driving IgG secretion in IL-4-stimulated human B cells. CONCLUSION:
      Signals from TLR9, TACI, and CD40 are integrated to promote B-cell activation and
      differentiation.

PMID- 21741081
TI  - Dissociation and association of the embodied representation of tool-use verbs and
      hand verbs: An fMRI study.
AB  - Embodied semantic theories suppose that representation of word meaning and actual
      sensory-motor processing are implemented in overlapping systems. According to
      this view, association and dissociation of different word meaning should
      correspond to dissociation and association of the described sensory-motor
      processing. Previous studies demonstrate that although tool-use actions and hand
      actions have overlapping neural substrates, tool-use actions show greater
      activations in frontal-parietal-temporal regions that are responsible for motor
      control and tool knowledge processing. In the present study, we examined the
      association and the dissociation of the semantic representation of tool-use verbs
      and hand action verbs. Chinese verbs describing tool-use or hand actions without
      tools were included, and a passive reading task was employed. All verb conditions
      showed common activations in areas of left middle frontal gyrus, left inferior
      frontal gyrus (BA 44/45) and left inferior parietal lobule relative to rest, and
      all conditions showed significant effects in premotor areas within the mask of
      hand motion effects. Contrasts between tool-use verbs and hand verbs demonstrated
      that tool verbs elicited stronger activity in left superior parietal lobule, left
      middle frontal gyrus and left posterior middle temporal gyrus. Additionally,
      psychophysiological interaction analyses demonstrated that tool verbs indicated
      greater connectivity among these regions. These results suggest that the brain
      regions involved in tool-use action processing also play more important roles in
      tool-use verb processing and that similar systems may be responsible for word
      meaning representation and actual sensory-motor processing.

PMID- 21741082
TI  - Mannosyl-coated nanocomplexes from amphiphilic cyclodextrins and pDNA for site
      specific gene delivery.
AB  - Fully homogeneous facial amphiphiles consisting in a cyclodextrin (CD) platform
      onto which a polycationic cluster and a multi-tail hydrophobic moiety have been
      installed (polycationic amphiphilic CDs; paCDs) self-organized in the presence of
      plasmid DNA to form nanometric complexes (CDplexes) which exhibit broad-range
      transfection capabilities. We hypothesized that biorecognizable moieties located
      at the hydrophilic rim in the CD scaffold would be exposed at the surface of the
      corresponding nanoparticles after DNA-promoted aggregation, endowing the system
      with molecular recognition abilities towards cell receptors. This concept has
      been demonstrated by developing an efficient synthetic strategy for the
      preparation of multivalent polycationic glyco-amphiphilic CDs (pGaCDs). Self
      assembled nanoparticles obtained from mannosylated pGaCDs and pDNA (average
      hydrodynamic diameter 80 nm) have been shown to be specifically recognized by
      mannose-specific lectins, including concanavalin A (Con A) and the human
      macrophage mannose receptor (MMR). Further macrophage adhesion studies indicated
      that unspecific binding, probably due to electrostatic interactions with
      negatively charged cell membrane components, can also operate. The relative
      specific versus non-specific internalization is dependent on the pGaCD:pDNA
      proportion, being optimal at a protonable nitrogen/phosphate (N/P) ratio of 5.
      The resulting GlycoCDplexes were shown to specifically mediate transfection in
      Raw 264.7 (murine macrophage) cells expressing the mannose-fucose receptor in
      vitro. FACS experiments confirmed that transfection using these nanoparticles is
      mannose-dependent, supporting the potential of the approach towards vectorized
      gene delivery.

PMID- 21741083
TI  - The creation of a biomimetic interface between boron-doped diamond and
      immobilized proteins.
AB  - Immobilization of proteins on a solid electrode is to date done by chemical cross
      linking or by addition of an adjustable intermediate. In this paper we introduce
      a concept where a solid with variable surface properties is optimized to mediate
      binding of the electron-transfer protein Cytochrome c (Cyt c) by mimicking the
      natural binding environment. It is shown that, as a carbon-based material, boron
      doped diamond can be adjusted by simple electrochemical surface treatments to the
      specific biochemical requirements of Cyt c. The structure and functionality of
      passively adsorbed Cyt c on variously terminated diamond surfaces were
      characterized in detail using a combination of electrochemical techniques and
      atomic force microscopy with single-molecule resolution. Partially oxidized
      diamond allowed stable immobilization of Cyt c together with high electron
      transfer activity, driven by a combination of electrostatic and hydrophobic
      interactions. This surface mimics the natural binding partner, where coarse
      orientation is governed by electrostatic interaction of the protein's dipole and
      hydrophobic interactions assist in formation of the electron transfer complex.
      The optimized surface mediated electron transfer kinetics around 100 times faster
      than those reported for other solids and even faster kinetics than on self
      assembled monolayers of alkanethiols.

PMID- 21741084
TI  - Docosahexaenoic acid stimulates tube formation in first trimester trophoblast
      cells, HTR8/SVneo.
AB  - Angiogenesis is a key factor in the placentation process and vascular remodeling
      that involves several growth factors such as vascular endothelial growth factor
      (VEGF) and angiopoietin-like protein 4 (ANGPTL4). PPARs are involved in the
      placentation process but not much information is available on whether their
      ligands such as fatty acids have any effects on these processes. We therefore
      investigated the effect of fatty acids (arachidonic acid, 20:4 n-6(ARA),
      eicosapentaenoic acid, 20:5 n-3(EPA), docosahexaenoic acid, 22:6 n-3 (DHA) and
      oleic acid, 18:1 n-9 (OA)) on tube formation (as a measure of angiogenesis) on
      matrigel in the first trimester trophoblast cells, HTR8/SVneo. In addition we
      also investigated the effects of fatty acids on expression of genes involved in
      angiogenesis (VEGF and ANGPTL4) and lipid metabolism in these cells. Gene
      expression was determined after incubating these cells with different fatty acids
      for 24 h using real-time qRT-PCR, whereas VEGF and ANGPTL4 proteins were measured
      by respective ELISA kits. Of all the fatty acids tested, DHA increased tube
      formation to the greatest extent. DHA-induced increase in tube length was 583%,
      247% and 70% over control, OA and EPA, respectively (p < 0.05). In addition, DHA
      stimulated cell proliferation by 150% of these cells. Of all fatty acids
      investigated, only DHA stimulated VEGF mRNA expression and protein secretion
      compared with control. Unlike DHA, other fatty acids (OA, EPA, ARA) stimulated
      ANGPTL4 mRNA expression and protein secretion in these cells. An inhibitor of
      VEGF decreased DHA stimulated tube formation in these cells. Altogether these
      data indicate that DHA may potently influence the placentation process by
      stimulating tube formation and this effect may be mediated in part via VEGF in
      first trimester trophoblast cells.

PMID- 21741085
TI  - Ca(2+) signaling mechanisms of cell survival and cell death: an introduction.

PMID- 21741086
TI  - Ouabain enhances exocytosis through the regulation of calcium handling by the
      endoplasmic reticulum of chromaffin cells.
AB  - The augmentation of neurotransmitter and hormone release produced by ouabain
      inhibition of plasmalemmal Na+/K+-ATPase (NKA) is well established. However, the
      mechanism underlying this action is still controversial. Here we have shown that
      in bovine adrenal chromaffin cells ouabain diminished the mobility of chromaffin
      vesicles, an indication of greater number of docked vesicles at subplasmalemmal
      exocytotic sites. On the other hand, ouabain augmented the number of vesicles
      undergoing exocytosis in response to a K+ pulse, rather than the quantal size of
      single vesicles. Furthermore, ouabain produced a tiny and slow Ca2+ release from
      the endoplasmic reticulum (ER) and gradually augmented the transient elevations
      of the cytosolic Ca2+ concentrations ([Ca2+]c) triggered by K+ pulses. These
      effects were paralleled by gradual increments of the transient catecholamine
      release responses triggered by sequential K+ pulses applied to chromaffin cell
      populations treated with ouabain. Both, the increases of K+-elicited [Ca2+]c and
      secretion in ouabain-treated cells were blocked by thapsigargin (THAPSI), 2
      aminoethoxydiphenyl borate (2-APB) and caffeine. These results are compatible
      with the view that ouabain may enhance the ER Ca2+ load and facilitate the Ca2+
      induced-Ca2+ release (CICR) component of the [Ca2+]c signal generated during K+
      depolarisation. This could explain the potentiating effects of ouabain on
      exocytosis.

PMID- 21741087
TI  - Effects of uranium uptake on transcriptional responses, histological structures
      and survival rate of the crayfish Procambarus clarkii.
AB  - This work aims to investigate the accumulation levels and effects
      (transcriptional responses, histopathology and survival rate) associated with a
      wide range of dissolved uranium (U) concentrations (0, 0.03, 0.6, 4 and 8 mg/L of
      U) on adult male crayfish Procambarus clarkii during 4 (T4) and 10 (T10) days of
      exposure. The follow-up of the crayfish mortality showed that P. clarkii was
      highly resistant to U. Increasing waterborne U concentrations led to increasing
      bioaccumulation in key crayfish organs and increasing histological damages. U
      distribution in tissues was also evaluated using transmission electron microscopy
      and showed the presence of a detoxified form of U in the gill's epithelium in the
      shape of flakes. Expression levels of mitochondrial genes (cox1, atp6 and 12S
      gene) and genes involved in oxidative stress (sod(Mn) and mt) were examined
      together with the housekeeping gene 18S. atp6 and mt genes of P. clarkii were
      cloned and sequenced before analysis. Significant correlations were observed
      between U bioaccumulation and the down-regulation of both cox1 and sod(Mn) genes.
      This work provides a first U toxicogenomic and histopathological pattern of P.
      clarkii, identify U biomarkers and associate gene expression endpoints to
      accumulation levels. It also provides new insights into the mechanisms involved
      in U stress.

PMID- 21741088
TI  - Pharmacokinetic properties of infliximab in children and adults with Crohn's
      disease: a retrospective analysis of data from 2 phase III clinical trials.
AB  - BACKGROUND: Infliximab is a chimeric monoclonal antibody against TNFalpha. The
      pharmacokinetic (PK) properties of infliximab have been studied in several adult
      patient populations, but a literature search identified no reported comparative
      population PK properties of this drug in pediatric patients. OBJECTIVES: The
      current analysis applied population PK techniques to compare data on the PK
      properties of infliximab in pediatric and adult patients with moderately to
      severely active Crohn's disease (CD) from 2 Phase III studies. METHODS: This
      analysis used serum infliximab concentration data from 692 patients (112
      children, 580 adults; age range, 6-76 years) from 2 Phase III clinical studies
      (REACH [A Randomized, Multicenter, Open-Label Study to Evaluate the Safety and
      Efficacy of Anti-TNF-alpha Chimeric Monoclonal Antibody in Pediatric Subjects
      with Moderate-to-Severe Crohn's Disease] and ACCENT I [A Crohn's Disease Clinical
      Trial Evaluating Infliximab in a New, Long-term Treatment Regimen]). PK models
      were developed separately for children, adults, and a combination of both. The
      combined population was used for establishing important covariates of infliximab
      PK properties in the combined CD population. Exploratory simulations using
      combined PK and covariate data were performed to expand the interpretation of the
      results in children. RESULTS: Based on the findings, in a typical child (who,
      based on the median values in REACH, weighs 42 kg, has a baseline serum albumin
      concentration [SAC] 3.8 mg/dL, and has not developed antibodies to infliximab
      [ATIs]) who is receiving infliximab and an immunomodulator, PK estimates (typical
      value [SE]) were as follows: clearance (CL), 5.43 (0.15) mL/kg/d; V(d) in the
      central compartment (V(1)), 54.2 (1.15) mL/kg; V(d) in the peripheral compartment
      (V(2)), 29.2 (2.03) mL/kg; and intercompartmental clearance (Q), 3.52 (0.71)
      mL/kg/d. Corresponding properties in a typical adult (weight, 68 kg; SAC, 4.1
      mg/dL) were CL, 5.39 (0.13) mL/kg/d; V(1), 52.7 (0.49) mL/kg; V(2), 19.0 (1.53)
      mL/kg; and Q, 2.15 (0.39) mL/kg/d. V(2) decreased as body weight increased,
      predicting a possible undercompensation for exposure with infliximab dosing per
      kg weight in lower-weight individuals. In pediatric and adult patients, CL was
      higher in those in whom ATIs developed or who had low baseline SAC. Concurrent
      immunomodulator use (purine antimetabolites or methotrexate) was associated with
      a 14% decrease in CL. In the pediatric and adult patients, observed trough serum
      infliximab concentrations, median infliximab t(1/2) (in children, 13.2 days; and
      in adults, 12.4 days), and exploratory PK simulations predicted infliximab PK
      properties to be comparable between children and adults. CONCLUSIONS: Infliximab
      PK properties appeared to be comparable between pediatric and adult patients with
      CD. Specifically, in this select population using nonlinear mixed effects
      modeling, infliximab CL increased as SAC decreased. CL also increased with ATI
      formation but decreased with immunomodulator coadministration. Although weight
      affects infliximab PK properties (total CL and total Vd increased with total body
      weight while per kg CL and Vd decrease with total body weight), age was not found
      to influence infliximab PK in the age range tested (6-76 years).

PMID- 21741089
TI  - Efficacy and tolerability of self-titrated biphasic insulin aspart 70/30 in
      patients aged >65 years with type 2 diabetes: an exploratory post hoc subanalysis
      of the INITIATEplus trial.
AB  - BACKGROUND: The Initiation of Insulin to reach A1C Target (INITIATEplus) trial
      studied the effect of self-titrating biphasic insulin aspart 70/30 (BiAsp 30)
      twice daily during 24 weeks in insulin-naive patients with type 2 diabetes who
      were poorly controlled by oral medication, and originally randomized according to
      frequency of dietary counseling interventions. OBJECTIVE: The purpose of this
      study was to compare the efficacy and tolerability of biphasic insulin aspart
      70/30 (BIAsp 30, NovoLog Mix 70/30) in INITIATEplus patients <=65 versus >65
      years old, irrespective of dietary counseling frequency, and to test the
      hypothesis that self-titrating BIAsp 30 in patients >65 years old could be well
      tolerated and effective in this age group. METHODS: An exploratory post hoc
      subanalysis, using standard statistical methods, was performed on patients
      stratified according to age. Data collected from 3492 patients in the intent-to
      treat population who were <=65 years old and 716 patients who were >65 years old
      compared glycosylated hemoglobin (HbA(1c)) and plasma glucose changes from
      baseline. Hypoglycemia rates and adverse event (AE) incidence were compared for
      the tolerability population of 4007 patients <=65 years old and 805 patients >65
      years old. RESULTS: Baseline-adjusted HbA(1c) changes for patients <=65 versus
      >65 years old were -2.38% versus -2.73% (P < 0.0001), with final HbA(1c)
      achieving 7.55% and 7.06%, respectively. Thirty-nine percent of patients <=65
      years old achieved HbA(1c) <=7% compared with 51% of patients >65 years old.
      Baseline-adjusted fasting plasma glucose decreases were greater for the >65 year
      old population (85.2 vs 91.2 mg/dL; P = 0.004; <=65 vs >65 years old,
      respectively). Minor hypoglycemia was reported in 9.7% and 7.7% of patients <=65
      versus >65 years old, respectively (0.52 vs 0.41 episodes per patient per year
      [ppy]; P = 0.01). Major hypoglycemia occurred in 1.5% and 3.1% of patients (0.05
      vs 0.14 episodes ppy, <=65 vs >65 years old, respectively; P < 0.0001). Nocturnal
      major hypoglycemia was reported for 0.4% and 0.6% of patients (P = 0.0028),
      whereas nocturnal minor hypoglycemia was reported for 3.8% and 2.6% (P = 0.007)
      of patients <=65 and >65 years old, respectively. AEs were reported for 24% and
      28% of patients <=65 and >65 years old, respectively, serious AEs were reported
      for 4% and 9% of patients, respectively, and AE-related withdrawals were reported
      for 1.3% and 2% of patients, respectively. CONCLUSIONS: Self-titrated biphasic
      insulin aspart 70/30 was found to be well-tolerated and effective in type 2
      diabetes patients >65 years old, as well as in patients <=65 years old. HbA(1c)
      and fasting plasma glucose decreases were significantly (P < 0.05) higher for
      patients >65 years old versus patients <=65 years old. Tolerability was indicated
      by major and minor hypoglycemia rates at or below <0.5 episodes ppy in both age
      groups. Overall rates of AE and serious AEs were higher among patients > 65
      years; withdrawals related to AEs were 2% compared with 1.3% in the younger age
      group.

PMID- 21741090
TI  - Review of the therapeutic uses of liraglutide.
AB  - BACKGROUND: Glucagon-like peptide (GLP-1) is a neuroendocrine hormone that
      increases blood glucose and is a drug target for treatment of type 2 diabetes.
      Liraglutide, a subcutaneous, once-daily GLP-1 agonist, is approved for the
      treatment of type 2 diabetes in the United States and Europe. It also has been
      studied for weight loss. OBJECTIVE: The purpose of this article is to review all
      of the relevant literature on the chemistry, pharmacology, pharmacokinetics,
      metabolism, clinical trials, safety, drug interactions, cost, and place in
      therapy of liraglutide. METHODS: Literature searches of MEDLINE between 1969 and
      September 2010, International Pharmaceutical Abstracts between 1970 and September
      2010, American Diabetes Association Meeting abstracts (2008-2010), and European
      Association for the Study of Diabetes abstracts (2008-2010) were performed using
      liraglutide, Victoza, and NN2211 as key terms. RESULTS: Thirteen randomized
      controlled trials were identified and summarized. Liraglutide has been shown to
      increase glucose-dependent insulin release by 34% to 118% and reduce postprandial
      glucagon levels by 20%. Studies showed that liraglutide, as monotherapy and in
      combination with glimepiride, metformin, and/or rosiglitazone, lowers
      glycosylated hemoglobin (HbA(1c)) between 0.84% and 1.5%. Transient nausea was
      reported by 7% to 40% of subjects. Severe hypoglycemia-glucose <55 mg/dL-was
      observed by 2.5% of subjects in 1 trial. CONCLUSION: Liraglutide safely and
      effectively reduces HbA(1c) in patients with type 2 diabetes. The most recent
      American Diabetes Association guidelines recommended a GLP-1 agonist along with
      metformin as a second-tier therapy for type 2 diabetes. Although the American
      Association of Clinical Endocrinologists/American College of Endocrinologists'
      guidelines recommended it for first-line monotherapy in patients with HbA(1c)
      between 6.5% and 7.5% and with metformin if HbA(1c) is between 7.6% and 8.5%,
      liraglutide should be considered for patients who cannot tolerate first-line
      agents or if an additional agent is needed to help reach target HbA(1c) goals.

PMID- 21741091
TI  - Rifaximin: new therapeutic indication and future directions.
AB  - BACKGROUND: Rifaximin is a nonabsorbable oral antibiotic that acts locally in the
      gastrointestinal tract with minimal systemic adverse effects. Rifaximin received
      new labeling for reduction in the risk of the recurrence of overt hepatic
      encephalopathy (HE) in patients with advanced liver disease in March of 2010.
      OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, and
      pharmacodynamics of rifaximin. The efficacy and safety of rifaximin in reducing
      the risk of the recurrence of overt HE in patients with advanced liver disease,
      the new US Food and Drug Administration-approved indication, is the focus of this
      review. Emerging data on the use of rifaximin in irritable bowel syndrome (IBS)
      and Clostridium difficile infection (CDI) are also evaluated. METHODS: MEDLINE
      and International Pharmaceutical Abstracts from 1983 to January 31, 2011, were
      searched using the key terms rifaximin, L/105, secondary hepatic encephalopathy,
      irritable bowel syndrome, and Clostridium difficile. Ongoing trials were
      identified using the clinicaltrials.gov Web site. Abstracts from the annual
      meetings of the American College of Gastroenterology and Digestive Disease Week
      from 2004 to 2010 and references from relevant articles were reviewed. Only
      trials examining use of rifaximin in secondary prophylaxis of HE were included.
      Studies on the efficacy and safety of rifaximin in the treatment of acute
      episodes of HE have been recently summarized elsewhere and are not reviewed here.
      RESULTS: Literature search identified one trial on rifaximin use in secondary
      prevention of HE, six trials in patients with IBS, and six small studies and case
      reports in patients with CDI. In a trial of 299 patients, use of rifaximin 550 mg
      by mouth twice daily for 6 months for prevention of recurrent HE was associated
      with significantly fewer breakthrough HE episodes compared with placebo
      (rifaximin 22%, placebo 46%; P < 0.001), with a hazard ratio of 0.42 (95% CI,
      0.28-0.64). The rifaximin group also had fewer hospitalizations involving HE
      compared with placebo (rifaximin 13.6%, placebo 22.6%; P = 0.01), with a hazard
      ratio of 0.50 (95% CI, 0.29-0.87). Rifaximin improved IBS symptom management in
      ~9% more patients than placebo in 2 prospective, randomized, double-blind,
      placebo-controlled trials of 1260 patients (in the rifaximin group, 40.8%
      patients reported IBS symptom improvement compared with 31.7% in the placebo
      group; P < 0.001). The efficacy of rifaximin has been reported for the treatment
      of refractory or recurrent CDI in small studies, case series, and a case report.
      Optimal dosing, duration, and role of rifaximin for CDI management is unclear. In
      clinical trials of rifaximin for prevention of recurrent HE and for
      nonconstipated IBS, its safety profile was comparable to placebo. In the trial of
      rifaximin for prevention of recurrent HE, the most common adverse events
      occurring in 10% to 15% of patients were ascites, dizziness, fatigue, and
      peripheral edema. Most common adverse effects in IBS trials included abdominal
      pain, diarrhea, bad taste, headache, and upper respiratory tract infection,
      occurring in <10% of patients. CONCLUSIONS: Rifaximin can be an effective option
      for reduction in the risk of the recurrence of HE in patients with advanced liver
      disease. Studies suggest that rifaximin provides relief of global symptoms of
      diarrhea-predominant IBS and bloating. Use of rifaximin in CDI requires further
      study.

PMID- 21741092
TI  - Immunologic effects and tolerability profile of in-season initiation of a
      standardized-quality grass allergy immunotherapy tablet: a phase III,
      multicenter, randomized, double-blind, placebo-controlled trial in adults with
      grass pollen-induced rhinoconjunctivitis.
AB  - BACKGROUND: The summary of product characteristics of the grass allergy
      immunotherapy tablet (AIT) (Phleum pratense grass pollen allergen extract) states
      that clinical effect may be observed in the first pollen season of treatment, if
      treatment is initiated >=2 months (8 weeks) before the start of the grass pollen
      season. However, because patients with grass allergy may first present to
      physicians during the season, immediate treatment initiation (ie, in-season
      initiation) may increase treatment compliance and reduce the risk for disease
      progression compared with asking patients to return before the next pollen season
      to initiate treatment. This "in-season approach" may offer more patients the
      potentially beneficial treatment option of specific immunotherapy. However, to
      date, the immunomodulatory effects and tolerability of in-season treatment
      initiation is unknown. OBJECTIVE: The aim of this study was to assess the
      immunologic effects and tolerability of in-season initiation of treatment with
      the grass AIT. METHODS: This multicenter, randomized, double-blind, placebo
      controlled trial was carried out in Germany and Austria. Adults with grass pollen
      allergy (positive skin-prick test and specific grass-pollen immunoglobulin [Ig]
      E) and grass pollen-induced moderate to severe persistent rhinoconjunctivitis
      were enrolled. Patients were randomly assigned to receive once-daily grass AIT or
      placebo, starting during the 2008 grass pollen season and continuing for 8 to 10
      weeks. The primary end point was change from baseline in IgE-blocking factor
      (serum components competing with IgE for allergen binding). Secondary end points
      included changes from baseline in specific IgE and IgG(4) and measures of
      tolerability (assessed mainly by adverse events [AEs]). Blood samples for
      immunologic assessment were obtained by the investigators at baseline and after
      treatment. All AEs observed by the investigator and/or reported by the patient
      were recorded throughout the trial and follow-up. RESULTS: A total of 276
      patients were enrolled and formed the full analysis set (mean age, 35 years; 55%
      men, 45% women; 99% white; mean weight, 76 kg; history of asthma, 41%; mean
      duration of grass allergy, 15.1 years). No major differences in medical history
      were found between the grass AIT group (n = 219) and the placebo group (n = 57).
      The change from baseline in mean concentration of IgE-blocking factor was
      significantly greater with grass AIT compared with placebo (+0.14 vs +0.05; P <
      0.0001). The changes from baseline in specific IgE and specific IgG(4)
      concentrations were significantly greater with AIT compared with placebo (IgE,
      +0.59 vs +0.21 log kU/L; IgG(4), +0.18 vs +0.04 log relative units; both, P <
      0.0001). At least 1 AE was reported in 58% of patients in the AIT group and in
      40% of patients in the placebo group. Most AEs considered related to AIT were
      mild or moderate events in the mouth, throat, and/or ears (eg, oral pruritus).
      Four serious AEs were reported in the AIT group (sinusitis, road traffic
      accident, salmonellosis, meniscus lesion), but all were considered unlikely to be
      related to treatment. Three percent of the grass AIT group and 2% of the placebo
      group were withdrawn from the trial due to an AE. CONCLUSIONS: In-season
      initiation of grass AIT was associated with an immunomodulatory response in terms
      of induction of IgE-blocking factor, specific IgE, and specific IgG(4). In-season
      initiation of grass AIT was generally well tolerated in this group of adults with
      moderate to severe grass pollen-induced rhinoconjunctivitis. These findings are
      consistent with those related to the preseasonal initiation of AIT therapy.

PMID- 21741093
TI  - Influence of age on the dynamics of fMRI activations during a semantic fluency
      task.
AB  - PURPOSE: Age-related fMRI changes have not been extensively studied for language,
      whereas important adaptive mechanisms have been seen in other cognitive fields.
      This study examined age-related changes in fMRI activation during language tasks
      and, in particular, their dynamic course. PATIENTS AND METHODS: fMRI was
      performed on 22 young and 21 old healthy right-handed subjects during a silent
      category word-generation task. Activation and dynamics of BOLD signals were
      studied separately during the first and second portions of each 30-s block.
      RESULTS: Activation of the left frontal lobe was initially similar in young and
      old participants; however, it decreased after 30 s in the old participants. On
      the other hand, additional areas were initially involved only in old subjects and
      especially in the default mode network. CONCLUSION: This study showed age-related
      differences in the dynamics of fMRI activation during a silent word-generation
      task, suggesting a different pattern of language function with aging.

PMID- 21741094
TI  - Differential aberrant sprouting in temporal lobe epilepsy with psychiatric co
      morbidities.
AB  - Psychiatric co-morbidities in epilepsy are common in patients with temporal lobe
      epilepsy (TLE). Pathological alterations in TLE are well characterised; however,
      neuropathologic data are relatively scale regarding the association between
      psychiatric diseases and epilepsy. Our objective was to evaluate the clinical
      data of 46 adult TLE patients with and without psychiatric co-morbidities and to
      correlate the data with hippocampal neuronal density and mossy fiber sprouting.
      Accordingly, patients were grouped as follows: TLE patients without history of
      psychiatric disorder (TLE, n=16), TLE patients with interictal psychosis (TLE+P,
      n=14), and TLE patients with major depression (TLE+D, n=16). Hippocampi from
      autopsies served as non-epileptic controls (n=10). TLE+P exhibited significantly
      diminished mossy fiber sprouting and decreased neuronal density in the entorhinal
      cortex when compared with TLE. TLE+P showed significantly poorer results in
      verbal memory tasks. TLE+D exhibited significantly increased mossy fiber
      sprouting length when compared with TLE and TLE+P. Further, a higher proportion
      of TLE+D and TLE+P presented secondarily generalised seizures than did TLE. Our
      results indicate that TLE patients with psychiatric disorders have distinct
      features when compared with TLE patients without psychiatric co-morbidities and
      that these changes may be involved in either the manifestation or the maintenance
      of psychiatric co-morbidities in epilepsy.

PMID- 21741095
TI  - Diagnostic and statistical manual of mental disorders.

PMID- 21741096
TI  - Ototoxicity of Povidone-Iodine applied to the middle ear cavity of guinea pigs.
AB  - OBJECTIVE: Povidone-Iodine preparation is used as a disinfectant in otological
      surgeries. The ototoxicity of Povidone-Iodine preparation was evaluated using
      infant, young and adult guinea pigs. The effects of different concentrations and
      of different exposure durations on compound action potentials were also studied.
      MATERIALS & METHODS: Povidone-Iodine was used to fill one middle ear cavity of
      the guinea pig, and the compound action potential (CAP) was measured from the
      round window membrane at 24h, 7 days, and 28 days. The contralateral side was
      filled with saline as control. Test sounds used were clicks and tone bursts of 2,
      4, and 8 kHz. RESULTS: At 24h, Povidone-Iodine solution showed a significant
      toxic effect in the infant group. In the young animal group, no toxic effect was
      seen. In the adult group, a mild degree of deafness for 2 kHz was found. At 7
      days, the young group showed significant hearing loss for all frequencies, but
      the adult group did not show any hearing loss. With a half strength solution,
      both young and adult group did not show hearing loss. At 28 days, with a full
      strength solution, hearing loss became prominent for all sound stimulation. With
      1/8th dilution, the young group showed a moderate hearing loss, but the adult
      group did not. CONCLUSION: The thicker round window membrane in human is expected
      to provide more protection to the human cochlea than in the guinea pig model that
      we have studied. Mild hearing loss at 24h and 7 days using 10% solution, but no
      hearing loss with 5% solution at 7 days may indicate that rinsing of the middle
      ear cavity with saline during surgery should minimize the ototoxic effect of this
      product. The age of the animals does influence the outcome of the ototoxicity
      experiment. From this experiment, Povidone-Iodine preparations in the infant
      should be used with caution. Povidone scrub should not be used for otologic
      surgery.

PMID- 21741097
TI  - Mast cells squeeze the heart and stretch the gird: their role in atherosclerosis
      and obesity.
AB  - Mast cells are crucial for the development of allergic and anaphylactic
      reactions, but they are also involved in acquired and innate immunity. Increasing
      evidence now implicates mast cells in inflammatory diseases through activation by
      non-allergic triggers such as neuropeptides and cytokines. This review discusses
      how mast cells contribute to the inflammatory processes associated with coronary
      artery disease and obesity. Animal models indicate that mast cells, through the
      secretion of various vasoactive mediators, cytokines and proteinases, contribute
      to coronary plaque progression and destabilization, as well as to diet-induced
      obesity and diabetes. Understanding how mast cells participate in these
      inflammatory processes could help in the development of unique inhibitors with
      novel therapeutic applications for these diseases, which constitute the greatest
      current threat to global human health and welfare.

PMID- 21741098
TI  - The axo-myelinic synapse.
AB  - Axons have evolved to acquire myelination, enabling denser packing and speedier
      transmission. Although myelin is considered a passive insulator, recent reports
      suggest a more dynamic role. Axons, in turn, are endowed with neurotransmitter
      release and uptake systems along their trunks. Based on these observations, I
      argue that there may exist a new type of chemical synapse between axon and
      myelin, one that supports activity-dependent communication between the two. This
      raises intriguing possibilities of dynamic fine-tuning of the myelin sheath even
      in adulthood, efficient recruitment of resources for myelin maintenance and bi
      directional signaling, whereby the axon informs its myelinating cell of its
      metabolic needs proportionally to the electrical traffic it is transmitting. This
      would also have implications for de- and dysmyelinating diseases should this axo
      myelinic synapse become dysfunctional.

PMID- 21741099
TI  - Assessment of the effects of the A3872G polymorphism on the C-reactive protein
      gene in patients with diabetes mellitus type 2.

PMID- 21741100
TI  - Left ventricular noncompaction presenting as peripartum cardiomyopathy.

PMID- 21741101
TI  - Takotsubo syndrome associated with seizures: the visible part of the iceberg?

PMID- 21741102
TI  - School buses, diesel emissions, and respiratory health.
AB  - School buses contribute disproportionately to ambient air quality, pollute near
      schools and residential areas, and their emissions collect within passenger
      cabins. This paper examines the impact of school bus emissions reductions
      programs on health outcomes. A key contribution relative to the broader
      literature is that we examine localized pollution reduction programs at a fine
      level of aggregation. We find that school bus retrofits induced reductions in
      bronchitis, asthma, and pneumonia incidence for at-risk populations. Back of the
      envelope calculations suggest conservative benefit-cost ratios between 7:1 and
      16:1.

PMID- 21741103
TI  - Comparison of modulated electron radiotherapy to conventional electron boost
      irradiation and volumetric modulated photon arc therapy for treatment of tumour
      bed boost in breast cancer.
AB  - BACKGROUND AND PURPOSE: To compare few leaf electron collimator (FLEC)-based
      modulated electron radiotherapy (MERT) to conventional direct electron (DE) and
      volumetric modulated photon arc therapy (VMAT) for the treatment of tumour bed
      boost in breast cancer. MATERIALS AND METHODS: Fourteen patients with breast
      cancer treated by lumpectomy and requiring post-operative whole breast
      radiotherapy with tumour bed boost were planned retrospectively using
      conventional DE, VMAT and FLEC-based MERT. The planning goal was to deliver 10Gy
      to at least 95% of the tumour bed volume. Dosimetry parameters for all techniques
      were compared. RESULTS: Dose evaluation volume (DEV) coverage and homogeneity
      were best for MERT (D(98)=9.77Gy, D(2)=11.03Gy) followed by VMAT (D(98)=9.56Gy,
      D(2)=11.07Gy) and DE (D(98)=9.81Gy, D(2)=11.52Gy). Relative to the DE plans, the
      MERT plans predicted a reduction of 35% in mean breast dose (p<0.05), 54% in mean
      lung dose (p<0.05) and 46% in mean body dose (p<0.05). Relative to the VMAT
      plans, the MERT plans predicted a reduction of 24%, 36% and 39% in mean breast
      dose, heart dose and body dose, respectively (p<0.05). CONCLUSIONS: MERT plans
      were a considerable improvement in dosimetry over DE boost plans. There was a
      dosimetric advantage in using MERT over VMAT for increased DEV conformity and low
      dose sparing of healthy tissue including the integral dose; however, the cost is
      often an increase in the ipsilateral lung high-dose volume.

PMID- 21741104
TI  - Aflatoxins and ochratoxin A in stored barley grain in Spain and impact of PCR
      based strategies to assess the occurrence of aflatoxigenic and ochratoxigenic
      Aspergillus spp.
AB  - Contamination of barley by moulds and mycotoxins results in quality and
      nutritional losses and represents a significant hazard to the food chain. The
      presence of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) and
      ochratoxin A (OTA) in stored barley in Spain has been studied. Species-specific
      PCR assays were used for detection of Aspergillus flavus, A. parasiticus, A.
      ochraceus, A. steynii, A. westerdijkiae, A. carbonarius and A. niger aggregate in
      mycotoxin-positive barley samples at different incubation times (0, 1 and 2
      days). Classical enumeration techniques (CFU/g) in different culture media for
      evaluation of Aspergillus in sections Flavi, Circumdati and Nigri were also used.
      One hundred and five barley kernel samples were collected in Spanish grain stores
      from 2008 to 2010, and analyzed using a previously optimized method involving
      accelerated solvent extraction, cleanup by immunoaffinity column, liquid
      chromatographic separation, post-column derivatization with iodine and
      fluorescence detection. Twenty-nine samples were contaminated with at least one
      of the studied mycotoxins. AFB1, AFB2, AFG1, AFG2, and OTA were detected in
      12.4%, 2.9%, 4.8%, 2.9%, and 20% of the samples, respectively. Aflatoxins and OTA
      co-occurred in 4.8% of the samples. Maximum mycotoxin levels (ng/g) were 0.61
      (AFB1), 0.06 (AFB2), 0.26 (AFG1), 0.05 (AFG2), and 2.0 (OTA). The results of PCR
      assays indicated the presence of all the studied species, except A.
      westerdijkiae. The PCR assays showed high levels of natural contamination of
      barley with the studied species of Aspergillus which do not correspond to the
      expected number of CFU/g in the cultures. These results suggest that a high
      number of non-viable spores or hyphae may exist in the samples. This is the first
      study carried out on the levels of aflatoxins and OTA in barley grain in Spain.
      Likewise, this is the first report on the presence of aflatoxigenic and
      ochratoxigenic Aspergillus spp. in barley grain naturally contaminated with those
      mycotoxins using a species-specific PCR approach.

PMID- 21741105
TI  - In vitro evaluation of gastrointestinal survival of Lactobacillus amylovorus DSM
      16698 alone and combined with galactooligosaccharides, milk and/or
      Bifidobacterium animalis subsp. lactis Bb-12.
AB  - Probiotic properties of Lactobacillus amylovorus DSM 16698 were previously
      demonstrated in piglets. Here, its potential as a human probiotic was studied in
      vitro, using the TIM-1 system, which is fully validated to simulate the human
      upper gastrointestinal tract. To evaluate the effect of the food matrix
      composition on the survival of L. amylovorus DSM 16698 in TIM-1, the
      microorganism was inoculated alone or with prebiotic galactooligosaccharides
      (GOS), partially skimmed milk (PSM) and/or commercial probiotic Bifidobacterium
      animalis subsp. lactis Bb-12 (Bb-12). Samples were collected from TIM-1 for six
      hours, at one-hour intervals and L. amylovorus populations were enumerated on MRS
      agar plates with confirmation of identity of selected isolates by randomly
      amplified polymorphic DNA (RAPD) fingerprinting. The cumulative survival for L.
      amylovorus alone (control) was 30% at the end of the experiment (t=6h). Co
      administration of L. amylovorus with GOS, PSM and/or Bb-12 increased its survival
      in comparison with the control significantly from the 4th hour after ingestion
      onwards (P<0.05). Furthermore, by the use of High Performance Anion Exchange
      Chromatography, both L. amylovorus and Bb-12 were observed to promptly degrade
      GOS compounds in samples collected from TIM-1, as assessed at t=2h. Hence, food
      matrix composition interfered with survival and growth of L. amylovorus during
      passage through TIM-1, providing leads towards optimization of probiotic
      properties in vivo.

PMID- 21741106
TI  - Nerve excitability properties in early preclinical diabetic neuropathy.
AB  - Diabetic polyneuropathy can be easily diagnosed when the nerve conduction studies
      are affected. Strength Duration Time (SDTc) reflects nerve excitability
      properties and was previously used several times to demonstrate the excitability
      properties of the nerves in the existence of electrophysiologically developed
      diabetic polyneuropathy. But as we all know, diabetic patients may experience
      neuropathic symptoms even though their routine nerve conduction studies are
      normal. SDTc may be useful in this early stages of developing neuropathy. In this
      study we aimed to evaluate the SDTc properties of diabetic patients in this early
      preclinic stage. Recently SDTc was commonly studied in the upper extremities but
      most of the diabetic neuropathies are predominant in the lower extremities. So
      here we also studied both upper and lower extremities to demonstrate a possible
      difference.

PMID- 21741107
TI  - HbA1c, fasting plasma glucose and the prediction of diabetes: Inter99, AusDiab
      and D.E.S.I.R.
AB  - INTRODUCTION: With diabetes defined by HbA1c>=6.5% and/or FPG>=7.0mmol/l and/or
      diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG)
      thresholds/change-points above which the incidence of diabetes increases.
      METHODS: Data are Danish (Inter99), Australian (AusDiab) and French (D.E.S.I.R.),
      with respectively 4930, 6012 and 3784 non-diabetic participants. RESULTS:
      Diabetes incidences at 5 years for Inter99 and AusDiab and at 6 years for
      D.E.S.I.R. were 2.3%, 3.1% and 2.4% respectively and incidences increased with
      baseline HbA1c and FPG. As HbA1c distributions differed between cohorts, HbA1c
      was standardized on D.E.S.I.R. data. Change-points where diabetes incidence
      increased were identified for HbA1c (%) after standardization: 5.1 (4.9-5.6)
      (Inter99), 5.4 (5.1-5.6) (AusDiab), 5.3 (5.1-5.7) (D.E.S.I.R.); for FPG change
      points (mmol/l) were 5.1 (...-6.1) (Inter99), 5.5 (5.2-5.8) (AusDiab), no change
      point for D.E.S.I.R. Using current diabetes risk criteria HbA1c>=5.7% and/or
      FPG>=5.6mmol/l to screen for diabetes provided high sensitivity (over 89%) and
      positive predictive values: 4.3%, 6.9%, and 5.9% respectively. CONCLUSIONS: HbA1c
      and FPG change-points predicting incident diabetes did not always exist, differed
      across studies, when available were generally lower than current criteria with
      wide confidence intervals. Using jointly HbA1c>=5.7% and/or FPG>=5.6mmol/l as a
      criterion for the risk of incident diabetes is appropriate.

PMID- 21741108
TI  - Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with
      development of preeclampsia in type 1 diabetes.
AB  - The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and
      Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study
      documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic
      women subsequently developing preeclampsia suggesting that preeclampsia is
      associated with cardiovascular changes in early pregnancy.

PMID- 21741109
TI  - RNA in pieces.
AB  - Eukaryotic genomes accommodate numerous types of information within diverse DNA
      and RNA sequence elements. At many loci, these elements overlap and the same
      sequence is read multiple times during the production, processing, localization,
      function and turnover of a single transcript. Moreover, two or more transcripts
      from the same locus might use a common sequence in different ways, to perform
      distinct biological roles. Recent results show that many transcripts also undergo
      post-transcriptional cleavage to release specific fragments, which can then
      function independently. This phenomenon appears remarkably widespread, with even
      well-documented transcript classes such as messenger RNAs yielding fragments. RNA
      fragmentation significantly expands the already extraordinary spectrum of
      transcripts present within eukaryotic cells, and also calls into question how the
      'gene' should be defined.

PMID- 21741110
TI  - SAE: an R package for early stopping rules in clinical trials.
AB  - In the case of an unexpected high frequency of serious adverse events (SAE),
      statistical methods are needed to help in the decision making process as to
      continuation of accrual to the trial. This paper describes an R package, named
      SAE that implements a method recently developed by defining stopping rules after
      each observed SAE. The package function control for excessive toxicity either
      during the trial at the observation of each SAE (function SAE) or during the
      planning phase of a clinical trial (function DESIGN). This description and the
      package documentation are complementary to help the users to apply the method.
      The main difficulty in the implementation of the method is the choice of a priori
      parameters. Data from an ongoing clinical trial are presented as an example to
      improve the understanding and the use of the package.

PMID- 21741111
TI  - Community-associated meticillin-resistant Staphylococcus aureus strains as a
      cause of healthcare-associated infection.
AB  - Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) was
      first noticed as a cause of infection in community-based individuals without
      healthcare contact. As the global epidemic of CA-MRSA has continued, CA-MRSA
      strain types have begun to emerge as a cause of healthcare-associated infections
      (HAIs) and hospital outbreaks have occurred worldwide. In areas where CA-MRSA
      clones have become established with high prevalence, for example USA300 (ST8-IV)
      in the USA, CA-MRSA are beginning to supplant or overtake traditional healthcare
      associated MRSA strains as causes of HAI. The emergence of CA-MRSA as a cause of
      HAI puts a wider group of hospitalised patients, healthcare workers and their
      community contacts potentially at risk of MRSA infection. It also exposes CA-MRSA
      strains to the selective pressure of antibiotic use in hospitals, potentially
      resulting in increased antibiotic resistance, challenges traditional definitions
      of CA-MRSA and hampers control efforts due to the constant re-introduction of
      MRSA from an emerging community reservoir. There is thus an urgent need to
      clarify the definitions, prevalence and epidemiology of CA-MRSA and to develop
      systems for the identification and control of these organisms in the community,
      in hospitals and other healthcare facilities, and at the community-hospital
      interface.

PMID- 21741112
TI  - Changes in vancomycin-resistant Enterococcus faecium causing outbreaks in Brazil.
AB  - Enterococci have been implicated in severe human infections as a consequence of
      associated determinants of virulence and antimicrobial resistance. The majority
      of vancomycin-resistant Enterococcus faecium (VRE(fm)) connected to outbreaks
      worldwide pertains to the clonal complex 17 (CC17). In Brazil, the majority of
      VRE(fm) involved in outbreaks reported so far are not related to CC17. VRE(fm)
      strains responsible for an outbreak and sporadic cases in hospitals located in
      the city of Campinas, Brazil, were compared to other VRE(fm) strains in the
      country. Twenty-two out of 23 E. faecium were vancomycin-resistant and harboured
      the vanA gene. One vancomycin-susceptible E. faecium (VSE(fm)) strain was
      included in this study because it was isolated from a patient who one week later
      harboured a VRE(fm). All strains, except VSE, showed the same alteration in the
      VanA element characterised by deletion of the left extremity of the transposon
      and insertion of IS1251 between the vanS and vanH genes. Genes codifying
      virulence factors such as collagen-adhesin protein, enterococcal surface protein
      and hyaluronidase were detected in the VRE(fm) and VSE(fm) studied. Both pulsed
      field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed
      that VRE(fm) and VSE(fm) strains have a clonal relationship. New sequence types
      (STs) were identified by MLST as ST447, ST448, ST478 and ST412 but all belonged
      to the CC17. The present study revealed that VRE(fm) outbreaks in Brazil were
      caused by strains that did not share a common evolutionary history, and that
      VRE(fm) strains belonging to CC17 could be predominant in Brazil as in other
      countries.

PMID- 21741113
TI  - Investigation of classical epidemiological links between patients harbouring
      identical, non-predominant meticillin-resistant Staphylococcus aureus genotypes
      and lessons for epidemiological tracking.
AB  - According to molecular epidemiology theory, two isolates belong to the same chain
      of transmission if they are similar according to a highly discriminatory
      molecular typing method. This has been demonstrated in outbreaks, but is rarely
      studied in endemic situations. Person-to-person transmission cannot be
      established when isolates of meticillin-resistant Staphylococcus aureus (MRSA)
      belong to endemically predominant genotypes. By contrast, isolates of infrequent
      genotypes might be more suitable for epidemiological tracking. The objective of
      the present study was to determine, in newly identified patients harbouring non
      predominant MRSA genotypes, whether putative epidemiological links inferred from
      molecular typing could replace classical epidemiology in the context of a
      regional surveillance programme. MRSA genotypes were defined using double-locus
      sequence typing (DLST) combining clfB and spa genes. A total of 1,268 non
      repetitive MRSA isolates recovered between 2005 and 2006 in Western Switzerland
      were typed: 897 isolates (71%) belonged to four predominant genotypes, 231 (18%)
      to 55 non-predominant genotypes, and 140 (11%) were unique. Obvious
      epidemiological links were found in only 106/231 (46%) patients carrying isolates
      with non-predominant genotypes suggesting that molecular surveillance identified
      twice as many clusters as those that may have been suspected with classical
      epidemiological links. However, not all of these molecular clusters represented
      person-to-person transmission. Thus, molecular typing cannot replace classical
      epidemiology but is complementary. A prospective surveillance of MRSA genotypes
      could help to target epidemiological tracking in order to recognise new risk
      factors in hospital and community settings, or emergence of new epidemic clones.

PMID- 21741114
TI  - Laboratory diagnosis of Clostridium difficile infection in Spain: a population
      based survey.
AB  - A survey of laboratory diagnosis of Clostridium difficile infection (CDI) was
      conducted in 103 Spanish hospitals. A mean of 23.2 stool specimens/1000
      admissions were processed to detect CDI. Overall, 35.9% of the laboratories
      specifically selected stool specimens for diagnostic C. difficile toxin testing.
      The most commonly used criteria were loose or watery stools, previous antibiotic
      therapy and nosocomial diarrhoea. Most laboratories (95.1%) processed the stool
      specimens in house, mainly five to seven days/week. All laboratories except one
      detected toxins directly in stool specimens, and 94.9% used enzyme immunoassays
      (EIAs). Only 16.3% of the laboratories used toxigenic culture as a diagnostic
      tool, and most of them used EIAs to detect toxins in isolates. The most common
      diagnostic strategy was toxin detection in stool specimens using EIA alone
      (79.6%), and the second most common strategy was the combination of toxin
      detection in stool specimens and isolates (10.2%). The estimated annual incidence
      of CDI was 1.71 cases/1000 admissions, and this was significantly higher in large
      hospitals. CDI is underdiagnosed in Spain because most laboratories use EIAs
      performed directly on stool specimens as the only diagnostic procedure. A
      national laboratory survey of diagnostic methods and testing protocols for the
      diagnosis of CDI is simple and inexpensive, and could act as the first step
      towards implementing national standardized criteria for optimal diagnosis of CDI.

PMID- 21741115
TI  - Testing of the World Health Organization-recommended formulations for surgical
      hand preparation and proposals for increased efficacy.
AB  - The 2009 World Health Organization (WHO) Guidelines on hand hygiene in health
      care recommend alcohol-based hand rubs for both hygienic and pre-surgical hand
      treatment. Two formulations based on ethanol 80% v/v and 2-propanol 75% v/v are
      proposed for local preparation in healthcare settings where commercial products
      are not available or too expensive. Both formulations and our suggested
      modifications (using mass rather than volume percent concentrations) were
      evaluated for their conformity with the efficacy requirements of the forthcoming
      amendment of the European Norm (EN) 12791, i.e. non-inferiority of a product when
      compared with a reference procedure (1-propanol 60% v/v for 3 min) immediately
      and 3 h after antisepsis. In this study, the WHO-recommended formulations were
      tested for 3 min and 5 min. Neither formulation met the efficacy requirements of
      EN 12791 with 3 min application. Increasing the respective concentrations to 80
      w/w (85% v/v) and 75 w/w (80% v/v), together with a prolonged application of 5
      min, rendered the immediate effect of both formulations non-inferior to the
      reference antisepsis procedure. This was not the case with the 3h effect, which
      remained significantly inferior to the reference. Although the original
      formulations do not meet the efficacy requirements of EN 12791, the clinical
      significance of this finding deserves further clinical trials. To comply with the
      requirement of EN 12791, an amendment to the formulations is possible by
      increasing the alcohol concentrations through changing volume into mass percent
      and prolonging the duration of application from 3 min to 5 min.

PMID- 21741116
TI  - Peripheral-venous-catheter-related Staphylococcus aureus bacteraemia: a multi
      factorial approach to reducing incidence.

PMID- 21741117
TI  - Identifying new risk factors for Pseudomonas aeruginosa pneumonia in intensive
      care units: experience of the French national surveillance, REA-RAISIN.
AB  - Pseudomonas aeruginosa is an important pathogen of complicated pneumonia in
      intensive care units (ICUs). Our objective was to determine 'patient' and 'ward'
      risk factors for P. aeruginosa pneumonia among patients with nosocomial pneumonia
      in ICU. Data from the 2004-2006 prospective French national nosocomial infection
      surveillance in ICUs (REA-RAISIN) were used, including patients admitted for >48
      h in ICU and who developed nosocomial pneumonia. Only first pneumonia was
      considered and categorised as either P. aeruginosa pneumonia or other micro
      organism pneumonia. Multilevel logistic regression model (patient as first level
      and ward as second) with P. aeruginosa pneumonia as binary outcome was performed.
      Of 3,837 included patients from 201 different wards, 25% had P. aeruginosa
      pneumonia. P. aeruginosa was significantly more frequent in late onset pneumonia.
      Higher probability of P. aeruginosa pneumonia was associated with higher age and
      length of mechanical ventilation, antibiotics at admission, transfer from a
      medical unit or ICU, and admission in a ward with higher incidence of patients
      with P. aeruginosa infections. Lower probability of P. aeruginosa was associated
      with traumatism and admission in a ward with high patient turnover. Our analyses
      identified a patient's profile and some ward elements that could make suspect P.
      aeruginosa in case of nosocomial pneumonia.

PMID- 21741118
TI  - A prospective study of central venous catheters placed in a tertiary care
      Emergency Department: indications for use, infectious complications, and natural
      history.
AB  - Despite successful efforts to improve overall central line-associated bloodstream
      infections (CLABSI) rates, little is known about CLABSI rates or even central
      venous catheter insertion practices in the Emergency Department. We sought to
      determine the baseline CLABSI rate for Emergency Department-inserted central
      venous catheters and to describe indications for placement, duration of use, and
      the natural history of these devices.

PMID- 21741119
TI  - Antibiotics nonadherence and knowledge in a community with the world's leading
      prevalence of antibiotics resistance: implications for public health
      intervention.
AB  - BACKGROUND: Community determinants of antibiotics nonadherence, an important
      contributor of antibiotics resistance, remained unclear. OBJECTIVES: Our
      objective was to investigate whether deficient antibiotics knowledge could
      contribute to nonadherence in a community with high prevalence of antibiotics
      resistance. METHODS: We recruited 465 people by random sampling from 5 urban
      areas in Hong Kong. A structured questionnaire was used to assess antibiotics
      knowledge and adherence. Adherence was defined as completing the most recent
      course of antibiotics entirely according to physicians' instructions. An
      antibiotics knowledge score ranging from 0 to 3 (highest) was composed based on
      the number of correctly answered questions. RESULTS: Of the 465 participants
      interviewed, 96.3% had heard of the term "antibiotics," and 80.6% recalled having
      previously received antibiotics prescription. Among the eligible 369 subjects,
      32.9% showed nonadherence. Percentages of participants with antibiotics knowledge
      scores of 0, 1, 2, and 3 were 11%, 27%, 33%, and 29%, respectively. There was a
      higher prevalence of nonadherence among people with lower antibiotics knowledge
      score (P < .001). Furthermore, people with nonadherence had a significantly lower
      mean antibiotics knowledge score (1.3 +/- 1.0 versus 2.0 +/- 0.9, P < .001), with
      no interaction with education (P < .05). Adjusted for potential confounders,
      antibiotics knowledge scores of 2, 1, and 0 independently predicted increased
      risk of nonadherence by 1-fold (odds ratio [OR], 2.00; 95% confidence interval
      [CI]: 1.01-3.94; P = .047), 4-fold (OR, 4.77; 95% CI: 2.30-9.92; P < .001), and
      17-fold (OR, 18.41; 95% CI: 6.92-48.97; P < .001) respectively, compared with the
      maximum score of 3. CONCLUSION: Lack of antibiotics knowledge is a critical
      determinant of nonadherence independent of education in the community.

PMID- 21741120
TI  - Dermal and pulmonary absorption of propan-1-ol and propan-2-ol from hand rubs.
AB  - BACKGROUND: It has been shown that nontoxic concentrations of ethanol are
      absorbed after hand hygiene using ethanol-based hand rubs. This study
      investigated whether absorption of propan-1-ol and propan-2-ol from commercially
      available hand rubs results in measurable concentrations after use. METHODS: The
      pulmonary and dermal absorption of propanol during hand rubs was investigated.
      Rubs contained 70% (w/w) propan-1-ol, 63.14% (w/w) propan-2-ol, or 45% (w/w)
      propan-2-ol in combination with 30% (w/w) propan-1-ol. RESULTS: Peak median blood
      levels were 9.15 mg/L for propan-1-ol and 5.3 mg/L for propan-2-ol after hygienic
      hand rubs and 18.0 mg/L and 10.0 mg/L, respectively, after surgical hand rubs.
      Under actual surgical conditions, the highest median blood levels were 4.08 mg/L
      for propan-1-ol and 2.56 mg/L for propan-2-ol. The same procedure performed with
      prevention of pulmonary exposure through the use of a gas-tight mask resulted in
      peak median blood levels of 1.16 mg/L of propan-1-ol and 1.74 mg/L of propan-2
      ol. CONCLUSION: Only minimal amounts of propanols are absorbed through the use of
      hand rubs. Based on our experimental data, the risk of chronic systemic toxic
      effects caused by hand rubs is likely negligible. However, our study did not
      evaluate the consequences of long-term daily and frequent use of hygienic hand
      rubs.

PMID- 21741121
TI  - Control of Legionella contamination in a hospital water distribution system by
      monochloramine.
AB  - BACKGROUND: We report the results of 1-year application of monochloramine to
      control Legionella pneumophila contamination in a hospital hot water distribution
      system. METHODS: In the main building of the hospital, a device continuously
      distributing monochloramine was installed. Legionella pneumophila and Pseudomonas
      spp contamination was followed in comparison with 2 other water networks in the
      same building using chlorine dioxide. RESULTS: Monochloramine significantly
      reduced the number of contaminated sites compared with baseline (from 97.0% to
      13.3%, respectively), chlorine dioxide device I (from 100% to 56.7%,
      respectively), and device II (from 100% to 60.8%, respectively). No positive
      sample exceeded 10(4) colony-forming units/L versus 59.4% at baseline.
      CONCLUSION: Monochloramine could represent a good alternative to chlorine dioxide
      in controlling legionellae contamination in public and private buildings.

PMID- 21741122
TI  - Lower associated costs using rifampicin-miconazole-impregnated catheters compared
      with standard catheters.
AB  - Previous cost-effectiveness analyses found that antibiotic-impregnated catheters
      decrease the incidence of catheter-related bloodstream infection (CRBSI) as well
      as the costs related to central venous catheter (CVC) use, including increased
      hospital length of stay. The effect varied greatly among the studies, however. In
      this retrospective cohort study, compared with standard catheters, the use of
      rifampicin-miconazole-impregnated catheters was associated with lower CRBSI
      incidence and immediate CVC-related costs (taking into account only the costs of
      CVC, diagnosis, and treatment of CRBSI) (P < .001). Our data indicate that the
      use of rifampicin-miconazole-impregnated catheters can save associated costs.

PMID- 21741123
TI  - Ataxin-2 intermediate-length polyglutamine: a possible risk factor for Chinese
      patients with amyotrophic lateral sclerosis.
AB  - Intermediate-length polyglutamine (polyQ) expansions in the ataxin-2 (ATXN2) gene
      have recently been identified as a risk factor for sporadic amyotrophic lateral
      sclerosis (SALS). Our study aims to analyze cytosine, adenine, guanine (CAG)n
      expansions in the ATXN2 gene among Chinese patients with SALS. All patients
      diagnosed with adult-onset sporadic amyotrophic lateral sclerosis (ALS) were
      consecutively followed up, and their clinical characteristics were collected. To
      measure the repeat length of ATXN2 polyQ, fluorescence-polymerase chain reaction
      products were analyzed on a 3100-Avant Genetic Analyzer Applied Biosystem (Foster
      City, CA, USA) using the ROC-500 size standard. Three hundred forty-five patients
      with SALS were studied. The mean age of onset was 51.38 +/- 12.45 years. ATXN2
      polyQ with a repeat length greater than 27 was found to be weakly associated with
      amyotrophic lateral sclerosis in our study. There was no significant difference
      in mean age of onset, gender, and onset site between the group of SALS patients
      with and without ATXN2 polyQ expansion greater than 27. Our finding provides
      evidence that the ATXN2 polyQ expansion greater than 27 might be a risk factor
      for Chinese SALS patients.

PMID- 21741124
TI  - Fyn knock-down increases Abeta, decreases phospho-tau, and worsens spatial
      learning in 3*Tg-AD mice.
AB  - Fyn kinase phosphorylates tau and exacerbates amyloid beta (Abeta)-mediated
      synaptic dysfunction. However, Fyn also increases the nonpathological cleavage of
      amyloid precursor protein (APP), suggesting opposing roles for Fyn in the
      pathogenesis of Alzheimer's disease (AD). To determine the effect of Fyn on both
      Abeta and tau pathologies, we crossed homozygous Alzheimer's disease triple
      transgenic (3*Tg) mice harboring mutations in amyloid precursor protein,
      presenilin-1, and tau with wild-type or Fyn knockout mice to generate
      Fyn(+/+)3*Tg(+/-) or Fyn(+/-)3*Tg(+/-) mice. We found that Fyn(+/-)3*Tg(+/-) mice
      had increased soluble and intracellular Abeta, and these changes were accompanied
      by impaired performance on the Morris water maze at 18 months. Fyn(+/-)3*Tg(+/-)
      mice had decreased phosphorylated tau at 15-18 months (as did Fyn knockout mice),
      but Fyn(+/-)3*Tg(+/-) mice had increased phosphorylated tau by 24 months. In
      addition, we observed that Fyn(+/-)3*Tg(+/-) males were delayed in developing
      Abeta pathology compared with females, and displayed better spatial learning
      performance at 18 months. Overall, these findings suggest that loss of Fyn at
      early stages of disease increases soluble Abeta accumulation and worsens spatial
      learning in the absence of changes in tau phosphorylation.

PMID- 21741125
TI  - AD synapses contain abundant Abeta monomer and multiple soluble oligomers,
      including a 56-kDa assembly.
AB  - Much evidence indicates that soluble amyloid beta (Abeta) oligomers are key
      mediators of early cognitive loss, but the localization and key peptide species
      remain unclear. We have used flow cytometry analysis to demonstrate that
      surviving Alzheimer's disease (AD) synapses accumulate both Abeta and
      phosphorylated tau (p-tau). The present experiments use peptide-specific X-map
      assays and Western blot analyses to identify the Abeta peptide species in
      synaptosome-enriched samples from normal human subjects, neurologic controls, and
      AD cases. Abeta40 peptide levels did not vary, but both Abeta42 and Abeta
      oligomers were increased in soluble AD extracts, with oligomer levels 20-fold
      higher in aqueous compared with detergent extracts. In Western blot analysis, a
      ladder of sodium dodecyl sulfate (SDS)-stable oligomers was observed in AD cases,
      varying in size from monomer, the major peptide observed, to larger assemblies up
      to about 200 kDa and larger. Multiple oligomers, including monomer, small
      oligomers, a 56-kDa assembly, and amyloid precursor protein (APP) were correlated
      with the Abeta level measured in flow cytometry-purified synaptosomes. These
      results suggest that multiple amyloid precursor protein processing pathways are
      active in AD synapses and multiple soluble oligomeric assemblies may contribute
      to synaptic dysfunction.

PMID- 21741126
TI  - Cystamine and ethyl-eicosapentaenoic acid treatment fail to prevent malonate
      induced striatal toxicity in mice.
AB  - Cystamine has demonstrated neuroprotective activity in a variety of studies, and
      is currently being evaluated in a human clinical trial in Huntington's disease
      (HD). Cystamine treatment of various genetic models of HD demonstrated protection
      against neurodegeneration and/or improvement in behavior. Given the need for a
      rapid screening tool for HD therapeutics, we assessed the potential therapeutic
      benefits of cystamine in a short-term acute toxicity murine model of striatal
      cell death. Cystamine did not provide neuroprotection against bilateral
      intrastriatal malonate injections in mice as measured by lesion size, loss of
      striatal volume, or decreased striatal neuronal counts. Similar results were
      obtained for treatment with another potential therapeutic agent that was
      protective in genetic mouse models of HD, the essential fatty acid ethyl
      eicosapentaenoic acid. Our findings suggest that this toxic model is not
      reflective or predictive of findings in genetic mouse models, and may not be
      useful as a preclinical screen for HD therapeutics.

PMID- 21741127
TI  - Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers.
AB  - In this longitudinal study we investigated change over time in cerebrospinal
      fluid (CSF) levels of amyloid-beta 40 and 42 (Abeta40 and Abeta42), total tau
      (tau), tau phosphorylated at threonine 181 (ptau-181), isoprostane,
      neurofilaments heavy (NfH) and light (NfL). Twenty-four nondemented subjects, 62
      mild cognitive impairment (MCI) and 68 Alzheimer's disease (AD) patients
      underwent 2 lumbar punctures, with minimum interval of 6, and a mean +/- SD of 24
      +/- 13 months. Linear mixed models were used to assess change over time. Amyloid
      beta 42, tau, and tau phosphorylated at threonine 181, differentiated between
      diagnosis groups (p < 0.05), whereas isoprostane, neurofilaments heavy, and NfL
      did not. In contrast, effects of follow-up time were only found for nonspecific
      CSF biomarkers: levels of NfL decreased, and levels of isoprostane, amyloid-beta
      40, and tau increased over time (p < 0.05). Isoprostane showed the largest
      increase. In addition, increase in isoprostane was associated with progression of
      mild cognitive impairment to AD, and with cognitive decline as reflected by
      change in Mini Mental State Examination (MMSE). Contrary to AD-specific markers,
      nonspecific CSF biomarkers, most notably isoprostane, showed change over time.
      These markers could potentially be used to monitor disease progression in AD.

PMID- 21741128
TI  - TP53 Arg72Pro polymorphism in Turkish patients with sporadic amyotrophic lateral
      sclerosis.
AB  - Recently, Eve et al. (2007) reported that the expression of TP53 (NM_000546) was
      increased by 2.1-fold in whole spinal cord and 2.7-fold in the ventral horn of
      amyotrophic lateral sclerosis (ALS) patients. Based on this particular
      observation, we decided to evaluate whether the TP53 Arg72Pro polymorphism
      (rs1042522) (C215G) was implicated in the etiopathology of sporadic amyotrophic
      lateral sclerosis (SALS). Therefore, we genotyped 394 Turkish SALS patients and
      439 matched healthy controls by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). We did not find any association between overall
      SALS patients with the TP53 Arg72Pro polymorphism and controls (chi(2) = 2.674; p
      = 0.263). Consequently the TP53 Arg72Pro polymorphism was not associated with
      SALS.

PMID- 21741129
TI  - Resistance training and functional plasticity of the aging brain: a 12-month
      randomized controlled trial.
AB  - Maintaining functional plasticity of the cortex is essential for healthy aging
      and aerobic exercise may be an effective behavioral intervention to promote
      functional plasticity among seniors. Whether resistance training has similar
      benefits on functional plasticity in seniors has received little investigation.
      Here we show that 12 months of twice-weekly resistance training led to functional
      changes in 2 regions of cortex previously associated with response inhibition
      processes-the anterior portion of the left middle temporal gyrus and the left
      anterior insula extending into lateral orbital frontal cortex-in community
      dwelling senior women. These hemodynamic effects co-occurred with improved task
      performance. Our data suggest that resistance training improved flanker task
      performance in 2 ways: (1) an increased engagement of response inhibition
      processes when needed; and (2) a decreased tendency to prepare response
      inhibition as a default state. However, we highlight that this effect of
      resistance training was only observed among those who trained twice weekly;
      participants of the once-weekly resistance training did not demonstrate
      comparable response profiles, both in behavioral performance and hemodynamic
      activity in cortex. In sum, our findings suggest that twice-weekly resistance
      training in seniors can positively impact functional plasticity of response
      inhibition processes in cortex, and that it does so in a manner that complements
      the effects on selective attention that have previously been ascribed to aerobic
      exercise in seniors.

PMID- 21741130
TI  - 3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin
      inhibitors.
AB  - During a screening for compounds that could act against Mycobacterium
      tuberculosis, a series of new cellular antiproliferative agents was identified.
      The most cytotoxic molecules were evaluated against a panel of human cell lines
      derived from hematological and solid human tumors. In particular, (E)-2-(1H
      benzo[d] [1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)acrylonitrile (1) was found to
      be of a potency comparable to etoposide and greater than 6-mercaptopurine in all
      cell lines tested. Accordingly, a synthesis of a new series of (E)-2-(5,6
      dichloro-1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-R-phenyl)acrylonitriles was
      conducted in order to extend the studies of structure-activity relationship (SAR)
      for this class of molecules. With the aim to evaluate if 3-aryl-2-[1H
      benzotriazol-1-yl]acrylonitriles were able to act like tubulin binding agents,
      the effects on cell cycle distribution of the most active compounds (1, 2a, 3 and
      4) were analyzed in K562 cells. A detailed molecular modeling study of the
      putative binding mode of this series of compounds on tubulin is also reported.

PMID- 21741131
TI  - Targeting the human malaria parasite Plasmodium falciparum: in vitro
      identification of a new antiplasmodial hit in 4-phenoxy-2
      trichloromethylquinazoline series.
AB  - From the promising results we previously obtained in quinazoline series and to
      complete the evaluation of the in vitro antiplasmodial activity of original 2
      trichloromethylquinazolines, we synthesized new quinazolines possessing a
      variously substituted phenoxy group at position 4 through a simple and efficient
      two-step-synthesis approach. The studies of their activity toward the multi
      resistant W2 Plasmodium falciparum strain and of their cytotoxicity on the human
      hepatocyte HepG2 cell line highlighted a hit compound (molecule 7) displaying a
      W2 IC(50) value of 1.1 MUM and a HepG2 CC(50) value of 50 MUM, comparable to
      chloroquine and doxycycline. Structure-activity- and toxicity relationships
      indicate that the trichloromethyl group plays a key role in the antiplasmodial
      activity of such chemical scaffold and also that the phenoxy group substitution
      as a direct influence on the molecules selectivity. Moreover, molecule 7 displays
      significant specific activity against the Plasmodium genus in comparison with
      Toxoplasma and does not show any mutagenic property at the Ames test.

PMID- 21741132
TI  - Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity
      and in vivo activity as free radical scavengers of chlorido(p-cymene) complexes
      of ruthenium(II) containing N-alkylphenothiazines.
AB  - Three new ruthenium(II) complexes 1-3 containing N-alkylphenothiazine molecules
      were synthesized by reaction of [RuCl(2)(eta(6)-p-cymene)](2) with chlorpromazine
      hydrochloride (1), trifluoperazine dihydrochloride (2) or thioridazine
      hydrochloride (3). The compounds of the general formula L[RuCl(3)(eta(6)-p
      cymene)] were characterized by elemental analysis and spectroscopic methods (FT
      IR, UV-Vis, (1)H and (13)C NMR). Complex 2 was structurally characterized by
      single crystal X-ray diffraction. In vitro cytotoxic activity of complexes 1-3
      were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast
      carcinoma), SW-480 (colon carcinoma) and IM9 (myeloma multiple cells). The
      highest cytotoxicity (12.1 <= IC(50) <= 17.3 MUM) and induced a total (SW-480) or
      almost total cell death (MCF-7, MDA-MB-453) at 25 MUM in 48 h of treatment were
      observed for complex 2. The influence of three different doses (0.4, 4.5 and 90.4
      MUM/kg bw) of complex 2 on activities of antioxidants enzymes (superoxide
      dismutase (SOD) and catalase (CAT)) and lactate dehydrogenase (LDH) were
      investigated under physiological conditions. The effects on nitrite production
      (NO(2)(-)) and level of erythrocytes malondialdehyde (MDA) in rats blood were
      evaluated, too.

PMID- 21741133
TI  - Synthesis and structural studies of pentacycloundecane-based HIV-1 PR inhibitors:
      a hybrid 2D NMR and docking/QM/MM/MD approach.
AB  - Pentacycloundecane (PCU) lactam-peptide based HIV protease inhibitors were
      synthesized and nanomolar activity against the resistance-prone wild type C-South
      African HIV protease is reported. NMR investigations indicated that the activity
      is related to the chirality of the PCU moiety and its ability to induce
      conformations of the coupled peptide side chain. EASY-ROESY NMR experiments gave
      information about the 3D structure of the cage peptides and 3D solution structure
      could be linked to the experimental IC(50) activity profile of the considered
      inhibitors. QM/MM/MD simulations of the inhibitors in solution confirmed the NMR
      observed conformations. Docking experiments and QM/MM/MD simulations of the
      inhibitor-HIV PR complexes were also performed. These computational results
      complimented the experimental inhibition activities and enabled us to report a
      unique binding mode for PCU-based inhibitors at the active site of HIV-protease
      enzyme. A conserved hydrogen bonding pattern between the norstatine type
      functional group of the PCU hydroxylactam and active site residues, ASP25/ASP25',
      was observed in all active compounds. The biological significance and possible
      mode of inhibition by PCU-based HIV PR inhibitors discussed herein provide us
      with a deeper understanding of the mode of action of these novel inhibitors. The
      PCU-peptides are between 6000 and 8500 time less toxic to human MT-4 cells than
      Lopinavir. This potentially creates new application avenues for these putative
      inhibitors to be investigated against a vast number of other disease-related
      proteases.

PMID- 21741134
TI  - [Evolution and follow-up of hunger strikers: experience from an interregional
      hospital secured unit].
AB  - PURPOSE: A hunger strike is a voluntary fast, performed to protest publicly
      against an issue deemed unfair. In the case of French prisoners, hospitalization
      in an interregional hospital secured units (UHSI) may be necessary. METHODS: A
      retrospective epidemiological study based on one UHSI medical records was
      performed on the period of May, 2006 to December, 2008, and focused on symptoms,
      outcomes and ethical problems encountered. RESULTS: Seven men and one woman with
      a mean age of 32.6 years were hospitalized in an UHSI, with nine episodes of
      hunger strike of a median duration of 57 days. Clinical symptoms began after two
      weeks of voluntary deprivation in the form of dizziness, weakness, muscle pain
      and headache. Laboratory tests showed hypoglycemia (<0.4g/L) on admission, 16.3%
      decrease of albumin after 40.5 days, and dehydration in case of thirst strike.
      The clinical tolerance was good and no patient presented Wernicke's
      encephalopathy. A diabetic patient developed acidocetosis during two hunger
      strikes. All hunger strikes were respected by medical staff, and treatment was
      based upon surveillance of symptoms, vitamin B and sweetened drinks
      administration and explanations of the clinical hazards on a daily basis.
      CONCLUSION: The special problem encountered in the medical management of these
      strikers was to convince them to accept treatments in order to avoid a coercive
      life-saving treatment as requested by French law.

PMID- 21741135
TI  - [Diagnostic value of lymphadenopathy associated with fever and inflammation of
      unknown origin: a study of 69 patients].
AB  - PURPOSE: The diagnosis of fever or inflammation of unknown origin (FUO/IUO) is
      guided by the search of clinical clues. Lymphadenopathy is thought to be helpful
      but its actual contribution has never been tested, and little is known about the
      main causes of FUO/IUO with lymphadenopathy. The aim of this study was to clarify
      these issues from the experience of two departments of internal medicine.
      METHODS: We retrospectively studied a cohort of 69 consecutive inpatients with
      FUO or IUO and lymphadenopathy, hospitalized from January 2002 to February 2008.
      The patients were coded according to the final diagnosis and age. Recorded data
      included lymph node location, fever, CRP level, lymphocyte and platelet counts,
      presence of hyperbasophilic cells, hypogammaglobulinemia, monoclonal gammopathy,
      LDH level, and the results of histological and or cytological lymph node
      examination. RESULTS: Malignancy accounted for 54%, granulomatosis for 23%,
      mainly of infectious (60%) or malignancy-related origin (18%), the group
      classified as non-specific adenitis represented 17% of the cases and systemic
      diseases 4%. Diagnosis was obtained by histological examination of a lymph node
      biopsy in 80% and by cytology alone in 13% of the patients; no correlation was
      found between anatomic location, clinical and biological data and any
      pathological group. Univariate age-independent analysis showed significant
      correlation between intra-abdominal lymphadenopathy (P=0.05), increased serum CRP
      (P=0.01) and LDH levels (P=0.05) and malignancy, whereas superficial unique lymph
      node location (P<0.05), absence of deep site location (P<0.01), and presence of
      hyperbasophilic cells (P<0.01) were all related to benign non specific adenitis.
      CONCLUSION: FUO/IUO with lymphadenopathy must be considered as a separate entity,
      mostly represented by malignancies and granulomatosis, mainly of infectious or
      malignancy related origin. Fever, intra-abdominal lymphadenopathy, serum CRP and
      LDH levels and hyperbasophilic cells are relevant indicators.

PMID- 21741136
TI  - Clinical simulation: a sine qua non of nurse education or a white elephant?
AB  - An emphasis has been placed on clinical skill development in nurse education
      curricula due to the expressed concern about nursing students' clinical
      competence at the point of registration. Hence, the use of clinical simulation as
      an educational tool has become increasingly popular. The aim of this article is
      to examine the learning theory that underpins clinical simulation by utilising
      Carper's patterns of knowing (1978) as a theoretical framework. It is revealed
      that there is a philosophical conflict between the different learning approaches
      required to meet all the expected learning outcomes. It would also appear that
      due to a paucity of the current evidence base that the cost benefits of clinical
      simulation are largely unknown. The implications of these limitations may in part
      be overcome by future research endeavours, judicious curriculum development and a
      pluralistic approach to the facilitation of clinical simulation.

PMID- 21741137
TI  - Investigating the embryo/larval toxic and genotoxic effects of gamma irradiation
      on zebrafish eggs.
AB  - Eggs/larval of freshwater fish (Danio rerio) were exposed to low dose rates of
      external gamma radiation (from 1 to 1000 mGy d(-1)) over a 20-day period, with
      the objective of testing the appropriateness of the 10 mGy d(-1) guideline
      suggested by the IAEA. The present study examines different endpoints, mortality
      and hatching time and success of embryos as well as the genotoxicity of gamma
      irradiations (after 48 h). The 20-day embryo-larval bioassay showed an enhanced
      larval resistance to starvation after chronic exposure to gamma irradiation (from
      low 1 mGy d(-1) to high dose rate 1000 mGy d(-1)) and an acceleration in hatching
      time. Gamma irradiation led to increased genotoxic damage Ito zebrafish egg (40
      50% DNA in tail in Comet assay) from the lowest dose rate (1 mGy d(-1)). Possible
      mechanisms of gamma radiotoxicity and implications for radioprotection are
      discussed.

PMID- 21741138
TI  - Pulsed radiofrequency modulation for lingual neuralgia.
AB  - Pulsed radiofrequency modulation (PRM) is a minimally invasive procedure that has
      been used successfully to treat neuropathic pain. Its use to treat lingual
      neuralgia has not to our knowledge been described previously, and we report a
      case.

PMID- 21741139
TI  - Oxidation of bisphenol F (BPF) by manganese dioxide.
AB  - Bisphenol F (BPF), an environmental estrogen, is used as a monomer in plastic
      industry and its environmental fate and decontamination are emerging concern.
      This study focused on the kinetics, influencing factors and pathways of its
      oxidation by MnO(2). At pH 5.5, about 90% of BPF was oxidized in 20 min in a
      solution containing 100 MUM MnO(2) and 4.4 MUM BPF. The reaction was pH
      dependent, following an order of pH 4.5 > pH 5.5 > pH 8.6 > pH 7.5 > pH 6.5 > pH
      9.6. Humic acids inhibited the reaction at low (<= pH 5.5) and high pH (>= pH
      8.6) at high concentrations. In addition, metal ions and anions also suppressed
      the reaction, following the order Mn(2+) > Ca(2+) > Mg(2+) > Na(+) and HPO(4)(2-)
      > Cl(-) > NO(3)(-) ~ SO(4)(2-), respectively. A total of 5 products were
      identified, from which a tentative pathway was proposed.

PMID- 21741140
TI  - Changes in the chemistry of acidified Adirondack streams from the early 1980s to
      2008.
AB  - Lakes in the Adirondack region of New York have partially recovered in response
      to declining deposition, but information on stream recovery is limited. Here we
      report results of Adirondack stream monitoring from the early 1980s to 2008.
      Despite a 50% reduction in atmospheric deposition of sulfur, overall increases in
      pH of only 0.28 and ANC of 13 MUeq L(-1) were observed in 12 streams over 23
      years, although greater changes did occur in streams with lower initial ANC, as
      expected. In the North Tributary of Buck Creek with high dissolved organic carbon
      (DOC) concentrations, SO(4)(2-) concentrations decreased from 1999 to 2008 at a
      rate of 2.0 MUmol L(-1) y(-1), whereas in the neighboring South Tributary with
      low DOC concentrations, the decrease was only 0.73 MUmol L(-1) y(-1). Ca(2+)
      leaching decreased in the North Tributary due to the SO(4)(2-) decrease, but this
      was partially offset by an increase in Ca(2+) leaching from increased DOC
      concentrations.

PMID- 21741141
TI  - Dental or skeletal relapse after sagittal split osteotomy advancement surgery?
      Long-term follow-up.
AB  - PURPOSE: To evaluate the short- and long-term stability of mandibular advancement
      surgery with sagittal split osteotomy (SSO), and to investigate when relapse
      occurs and identify variables contributing to relapse. PATIENTS AND METHODS:
      Thirty-six patients with Class II anomalies were included; the mean age at
      surgery was 33.0 years. All underwent SSO surgery and clinical and radiologic
      follow-up at 8 weeks, 1 year, and 13 years. Model analysis, cephalometric
      analysis, and clinical examinations were performed at each control. RESULTS: Mean
      overjet relapse from 8 weeks to 13 years was 2.3 mm (range, 0 to 7.0 mm). Between
      8 weeks and 1 year, mean overjet relapse was 0.6 mm (range, -1.0 to 4.0 mm), and
      it was 1.7 mm (range, -1.0 to 6.0 mm) between 1 year and 13 years. Overjet
      relapse greater than 4 mm was found in 13.9% of the patients. Mean overjet 1 year
      after surgery was 2.6 mm and was significantly increased compared with 8 weeks (P
      = .006). Mean overjet 13 years after surgery was 4.3 mm and was significantly
      increased compared with 1 year (P < .001). Inferior incisor line to nasion-B
      point was 29.0 degrees  at 8 weeks after surgery and 25.4 degrees  at 13 years (P
      = .001). Insignificant changes in the other cephalometric variables were found at
      follow-up. CONCLUSION: SSO advancement surgery is a relatively stable technique
      over time. Mean overjet relapse was found to be 2.3 mm after 13 years, following
      a continuous pattern over time. The cephalometric variables showed insignificant
      changes during follow-up, indicating that relapses are mainly of dental and not
      skeletal origin.

PMID- 21741142
TI  - Long-term results from soft and hard tissue augmentation by a modified
      vascularized interpositional periosteal-connective tissue technique in the
      maxillary anterior region.

PMID- 21741143
TI  - Expression of bone morphogenetic protein, vascular endothelial growth factor, and
      basic fibroblast growth factor in irradiated mandibles during distraction
      osteogenesis.
AB  - PURPOSE: The present study evaluated the expression of bone morphogenetic
      proteins (BMPs)-2, -4, -7, vascular endothelial growth factor (VEGF), and basic
      fibroblast growth factor (bFGF) in irradiated mandibles during distraction
      osteogenesis. MATERIALS AND METHODS: A total of 24 rabbits were randomly assigned
      to the control and experimental groups. Each rabbit in the experimental group
      underwent preoperative radiation to 9 Gy in 5 fractions. After 1 month, all
      rabbits underwent osteotomy and distraction osteogenesis with 7 days of latency.
      Three rabbits in the control and experimental groups were killed at day 7 (end of
      the latency period), day 12 (middle of active distraction), day 18 (end of active
      distraction), and day 25 (1 week after consolidation). The specimens were used
      for immunohistochemical staining and real-time polymerase chain reaction
      analysis. RESULTS: Histologically, at day 25, cortical bone formation was much
      better in the control group than in the radiotherapy group. In the radiotherapy
      group, the bone spicules were aligned in the direction of tension stress. At day
      12, the expression of BMP-2, -4, and -7 was elevated in the radiotherapy group
      compared with the control group. At day 25, the expression of BMP-2 was
      significantly greater in the radiotherapy group. At day 7, the expression of bFGF
      was significantly suppressed in the radiotherapy group. At day 12, the expression
      of bFGF and VEGF was significantly elevated in the radiotherapy group compared
      with the control group. At day 25, the expression of VEGF was significantly
      greater in the radiotherapy group. CONCLUSIONS: The results of our study have
      shown that radiotherapy changes the expression pattern of BMPs, VEGF, and bFGF.

PMID- 21741144
TI  - [Study of the benefits after body contouring surgery at the university hospital
      in Lille].
AB  - BACKGROUND: Cutting the excess of skin body contouring surgery in post-massive
      weight loss patients seems to only improve functional and aesthetic disorders.
      But other benefits can be determinated such as psychosocial effects. The first
      two are usually evaluated. The last two are rarely researched. The goal of this
      study is to evaluate the benefits of body contouring surgery by comparing patient
      satisfaction on these different aspects. METHODS: One hundred thirty-four
      patients with more that 30 kg's weight loss had body contouring surgery at the
      university hospital in Lille between June 2004 and June 2008. Seventy-eight
      patients agreed to respond to a study on quality-of-life improvements after body
      contouring surgery which evaluated aesthetic, functional, and psychosocial
      aspects. The data were compared before and after the surgery to assess the
      benefits of the surgery in these areas. RESULTS: All the aforementioned aspects
      were clearly improved with the body contouring surgery. However, the improvement
      in the physical aspects seems to be somehow disappointing, not living up to the
      patients expectations. Exactly 52.5 % of the patients wanted morphologic
      alteration, while the scars were well tolerated in 78.2 % of the cases. On the
      other hand, psychosocial discomfort was improved in ways not expected by the
      patients. Two new findings were remarkable: a decrease of 56.7 % in the sense of
      feeling depressed and an improvement in finding a job after body contouring
      surgery. CONCLUSION: The psychosocial improvements represent the true benefits of
      body contouring surgery.

PMID- 21741145
TI  - [Effectiveness of high-flow oxygen therapy with warm humidification in a COPD
      patient with chronic cough].

PMID- 21741146
TI  - [Influence of patient-prosthesis mismatch in the octogenarian undergoing surgery
      for aortic valve replacement due to severe stenosis].
AB  - INTRODUCTION AND OBJECTIVES: The clinical impact of patient-prosthesis mismatch
      on the outcome in octogenarians who undergo surgery for aortic valve replacement
      due to severe stenosis is unknown. Our objective was to quantify the frequency of
      some degree of patient-prosthesis mismatch and its impact on mortality and life
      quality. METHODS: We analyzed all the octogenarian patients who underwent surgery
      for aortic valve replacement due to severe stenosis in our center from February
      2004 to April 2009. Patient-prosthesis mismatch was considered to exist when the
      indexed effective orifice area was <= 0.85 cm2/m2. The influence of patient
      prosthesis mismatch on in-hospital mortality, medium-term survival, and New York
      Heart Association functional class was studied using an analysis adjusted for
      propensity score. RESULTS: Of 149 patients studied, 61.7% had some degree of
      patient-prosthesis mismatch (mean follow-up was 32.71 +/- 14.42 months). After
      adjusting for propensity score, there were no differences in in-hospital
      mortality (odds ratio=0.75; 95% confidence interval, 0.15-3.58; P=.72), medium
      term survival (hazard ratio=1; 95% confidence interval, 0.36-2.78; P=.99) or
      functional class during follow-up (odds ratio=1.46; 95% confidence interval,
      0.073-29.24; P=.8). CONCLUSIONS: Although moderate patient-prosthesis mismatch is
      a very common finding in octogenarian patients who undergo aortic valve
      replacement, its influence on mortality and quality of life does not seem to be
      relevant. The biological profile of elderly patients with lower metabolic
      requirements and limited physical activity could justify the results obtained.

PMID- 21741147
TI  - Anaphylaxis to Malaysian meat loaf.

PMID- 21741148
TI  - Female pelvic congenital malformations. Part II: sexuality, reproductive outcomes
      and psychological impact.
AB  - The second part of this review deals with the quality of life of patients with
      congenital pelvic malformations, focusing on the sexuality, reproductive outcomes
      and overall psychological impact of the women affected. The presence of deformed
      pelvic anatomy, congenital or iatrogenic, and therefore of altered urinary, anal
      or sexual functions, are not only a physical limitation but seriously compromise
      psychological health from childhood. These difficulties jeopardise the thorny
      path from childhood to adult life through adolescence, and if neglected, could be
      responsible for seriously impairing quality of life in adulthood, in terms of
      mental health and psychosocial functions. If, in the 1970s, the main objective
      was to save the lives of newborns/infants, nowadays the therapy concept looks
      beyond that, focusing on quality of life and aiming to establish a satisfactory
      sexual life, allow the possibility of becoming a parent and enable the successful
      psychosocial integration of the patient. Ensuring urinary and fecal continence as
      well as the possibility of normal sexual activity, are the basis for allowing a
      normal psychological growth during adolescence, which leads to a satisfactory
      life later on.

PMID- 21741149
TI  - The effect of raloxifene on telomerase expression in breast carcinoma samples
      from postmenopausal women.
AB  - OBJECTIVE: This study aims to evaluate the effect of raloxifene on the expression
      of human telomerase reverse transcriptase (hTERT) in invasive ductal breast
      carcinoma of postmenopausal women. STUDY DESIGN: This study included 20
      postmenopausal women with invasive, stage II, estrogen receptor-positive ductal
      carcinoma diagnosed by incisional biopsy, who received 60 mg of raloxifene orally
      for 28 days prior to definitive surgery. On the 29th day of treatment, definitive
      surgery was performed and a second tumor sample was taken for analysis. The
      catalytic subunit of telomerase (hTERT) was evaluated semiquantitatively by
      immunohistochemistry in the tumor samples obtained prior to and following
      raloxifene use and the results were analyzed using the McNemar test (p<0.05).
      RESULTS: The samples of 17 patients (85%) were classified as positive for
      telomerase expression prior to raloxifene treatment, while only 6 (30%) remained
      positive following raloxifene treatment (p<0.0026). CONCLUSION: In the present
      study, raloxifene significantly reduced the expression of hTERT in estrogen
      receptor-positive breast tumors from postmenopausal women.

PMID- 21741150
TI  - Antibiotic use and risk of gynecological cancer.
AB  - OBJECTIVES: Several studies addressed the association between antibiotic use and
      breast cancer risk. The objective of this study was to assess the association
      between antibiotic use and risk of cervical, ovarian, and uterine cancer. STUDY
      DESIGN: We carried out a population-based case-control study using data from
      Saskatchewan Health administrative databases (Canada) between the years 1981 and
      2000. Cases were matched to 4 controls, using incidence density sampling. The
      effect of dosage and timing of antibiotic use, over a minimum of 15 years before
      diagnosis, on cervical, ovarian, or uterine cancer risk was assessed. Number of
      prescriptions and number of pills were used as exposure definitions. The effect
      of different classes of antibiotics on cancer risk was also studied. RESULTS: A
      total of 1225 cancer cases [192 cervical, 445 ovarian, and 588 uterine] and 4900
      matched controls were included in this study. Antibiotic exposure (number of
      prescriptions) during the period of 1-15 years in the past was significantly
      associated with a reduced risk of cervical cancer; Relative Risk (RR)=0.40, 0.31,
      0.26, and 0.29 for the four exposure quartiles, respectively. No association was
      found for ovarian or uterine cancer. When number of pills was considered, similar
      results were found. There was no effect of the timing or class of antibiotic
      exposure on cervical cancer risk. CONCLUSIONS: Antibiotic exposure up to 15 years
      in the past was associated with a decreased risk of cervical cancer. The lack of
      temporal trends and the absence of class specific effects suggest a non-causal
      relationship.

PMID- 21741151
TI  - Evaluation of the effect of pelvic floor muscle training (PFMT or Kegel exercise)
      and assisted pelvic floor muscle training (APFMT) by a resistance device
      (Kegelmaster device) on the urinary incontinence in women: a randomized trial.
AB  - OBJECTIVE: To evaluate the effect of pelvic floor muscle training (PFMT) or Kegel
      exercise with and without assistance by a resistance device (Kegelmaster device)
      on the urinary incontinence in women. STUDY DESIGN: A randomized clinical trial
      was performed on 91 women with the complaint of urinary incontinence. In the
      assisted pelvic floor muscle training (APFMT) group (n=41), after complete
      training, Kegelmaster device were used twice daily for 15 min each session, for a
      total duration of 12 weeks. In the pelvic floor muscle training (PFMT) group
      (n=50) after complete training, kegel exercises were done (including perineal
      muscle contractions for 6-8s with 6s rest in between), twice daily for 15 min
      each session and for a total duration of 12 weeks. These two groups were then
      compared according to the scores of special questionnaires for quality of life,
      strength of pelvic floor muscles, capability to participate in social activities,
      severity of urinary incontinence, and the number of involuntary urine passage,
      taken before, and after 1 and 3 months after finishing interventions. RESULTS: 85
      women out of 91 women finished the study (46 in the PFMT group and 39 in the
      APFMT group). Strength of pelvic floor muscles, capability to participate in
      social activities, score of quality of life according to three world
      questionnaires of IQOL (incontinence Quality Of Life), IIQ (Incontinence Impact
      Questionnaire), UDI (Urogenital Distress Inventory), showed no difference between
      the two groups 1 and 3 months after interventions. Pair t test showed a
      significant improvement in both groups 1 and 3 months after intervention,
      according to IQOL score (P=0.000), UDI score (P=0.000), IIQ score (P=0.000),
      strength of pelvic floor muscles, (P=0.000), capability to participate in social
      activities (P=0.000), severity of urinary incontinence (P=0.000) and the number
      of involuntary urine passage (P=0.000). CONCLUSION: Pelvic floor muscle training
      with or without Kegelmaster show no apparent difference to each other, however,
      these two methods are effective for improvement of urinary incontinence in women.

PMID- 21741152
TI  - Levonorgestrel intra-uterine system as a treatment option for complex endometrial
      hyperplasia.
AB  - OBJECTIVE: The objective of this study was to evaluate the potential treatment of
      atypical and non-atypical endometrial hyperplasia with the levonorgestrel
      intrauterine system (LNG-IUS). STUDY DESIGN: A prospective observational study
      was undertaken at Queen's Medical Centre's menstrual disorder clinic between 2001
      and 2008. Women presenting with abnormal perimenopausal and postmenopausal
      bleeding, underwent an endometrial biopsy followed by the insertion of a
      levonorgestrel intrauterine system (LNG-IUS). The study population comprised of
      51 patients. The histology of 32 patients (Group A) showed complex hyperplasia
      without atypia, and in 19 patients (Group B), biopsy revealed atypical
      endometrial hyperplasia. These patients chose to be managed conservatively with
      repeat sampling of the endometrium. RESULTS: Group A: 28 (87.5%) patients out of
      32 had regression of their endometrial hyperplasia within the first 12 months of
      follow-up. Three of the patients achieved regression by 24 months increasing
      regression rate to 96.8% and the remaining one had a hysterectomy due to a rare
      side effect. Group B: 16 (84.2%) of 19 patients had regression of the atypical
      hyperplasia after treatment with the intrauterine system within 12 months of
      treatment. One patient achieved regression of the hyperplasia by 24 months and
      two patients went on to have surgical management due to persistent atypia and
      severe atypia respectively. CONCLUSION: This study contribute further evidence
      that illustrates that levonorgestrel intrauterine systems have a potential role
      in patients requiring non-operative management although close follow-up is
      essential.

PMID- 21741153
TI  - Regression of endometrial autografts in a rat model of endometriosis treated with
      etanercept.
AB  - OBJECTIVE: To determine the efficacy of anti-tumor necrosis factor therapy
      (etanercept) for treating endometriosis in the rat endometriosis model. STUDY
      DESIGN: A randomized, placebo-controlled, blinded study using rat endometriosis
      model. After the peritoneal implantation of endometrial tissue, twenty-eight
      Wistar female rats were randomized to two equal intervention groups: the control
      group and the etanercept-treated group. After measuring implant volume,
      pretreatment blood and peritoneal fluid samples were obtained. A vehicle
      treatment of 2 mL saline to the rats in control group and 0. 4 mg/kg etanercept
      SC once weekly were administered in the etanercept-treated group. After four
      weeks treatment period, the volumes and histopathological properties of the
      implants were evaluated. A scoring system was used to evaluate preservation of
      epithelia. Endometrial explants were evaluated immunohistochemically for tumor
      necrosis factor receptor type 2 (TNFR2). A scoring system was used to evaluate
      expression grade of TNFR2. RESULTS: There was not a significant difference in
      spherical volume between control (131.0 (60.3-501.2)) and treatment groups (72.8
      (31.2-149.6)) (p>0.025). There was a significant change in between the volumes of
      implants before and after treatment in etanercept group (p<0.05). At the end of
      the treatment significant differences among the groups were found in
      histopathological and immunohistochemical parameters (p<0.05) also histologic
      scores and HSCORES were decreased in the treatment group significantly (p<0.05).
      CONCLUSION: These results indicate that etanercept was found to effectively
      reduce the development of endometriosis in this experimental rat model.

PMID- 21741154
TI  - Estimating irrigation water demand in the Moroccan Draa Valley using contingent
      valuation.
AB  - Irrigation water management is crucial for agricultural production and livelihood
      security in Morocco as in many other parts of the world. For the implementation
      of an effective water management, knowledge about farmers' demand for irrigation
      water is crucial to assess reactions to water pricing policy, to establish a cost
      benefit analysis of water supply investments or to determine the optimal water
      allocation between different users. Previously used econometric methods providing
      this information often have prohibitive data requirements. In this paper, the
      Contingent Valuation Method (CVM) is adjusted to derive a demand function for
      irrigation water along farmers' willingness to pay for one additional unit of
      surface water or groundwater. An application in the Middle Draa Valley in Morocco
      shows that the method provides reasonable results in an environment with limited
      data availability. For analysing the censored survey data, the Least Absolute
      Deviation estimator was found to be a more suitable alternative to the Tobit
      model as errors are heteroscedastic and non-normally distributed. The adjusted
      CVM to derive demand functions is especially attractive for water scarce
      countries under limited data availability.

PMID- 21741155
TI  - Cadmium accumulation and tolerance of mahogany (Swietenia macrophylla) seedlings
      for phytoextraction applications.
AB  - Mahogany, a high biomass fast-growing tropical tree, has recently garnered
      considerable interest for potential use in heavy metal phytoremediation. This
      study performed hydroponic experiments with Cd concentration gradients at
      concentrations of 0, 7.5, 15, and 30 mg L(-1) to identify Cd accumulation and
      tolerance of mahogany (Swietenia macrophylla) seedlings as well as their
      potential for phytoextraction. Experimental results indicate that Cd inhibited
      mahogany seedling growth at the highest Cd exposure concentration (30 mg L(-1)).
      Nevertheless, this woody species demonstrated great potential for phytoextraction
      at Cd concentrations of 7.5 and 15 mg L(-1). The roots, twigs, and leaves had
      extremely large bioaccumulation factors at 10.3-65.1, indicating that the plant
      extracted large amounts of Cd from hydroponic solutions. Mahogany seedlings
      accumulated up to 154 mg kg(-1) Cd in twigs at a Cd concentration of 15 mg L(-1).
      Although Cd concentrations in leaves were <100 mg kg(-1), these concentrations
      markedly exceed the normal ranges for other plants. Due to the high biomass
      production and Cd uptake capacity of mahogany shoots, this plant is a potential
      candidate for remediating Cd-contaminated sites in tropical regions.

PMID- 21741156
TI  - Influence of needle gauge on in vivo ultrasound and microbubble-mediated gene
      transfection.
AB  - Ultrasound and microbubble-mediated gene transfection are potential tools for
      safe, site-selective gene therapy. However, preclinical trials have demonstrated
      a low transfection efficiency that has hindered the progression of the technique
      to clinical application. In this paper it is shown that simple changes to the
      method of intravenous injection can lead to an increase in transfection
      efficiency when using 6-MHz diagnostic ultrasound and the ultrasound contrast
      agent, SonoVue. By using needles of progressively smaller gauge, i.e., larger
      internal diameter (ID), from 29 G (ID 0.184 mm) to 25 G (ID 0.31 mm), the
      transfection of a luciferase plasmid (pGL4.13) was significantly increased
      threefold in heart-targeted female CD1 mice. In vitro work indicated that the
      concentration and size distribution of SonoVue were affected by increasing needle
      gauge. These results suggest that the process of systemic delivery alters the
      bubble population and adversely affects transfection. This is exacerbated by
      using high-gauge needles. These findings demonstrate that the needle with the
      largest possible ID should be used for systemic delivery of microbubbles and
      genetic material.

PMID- 21741157
TI  - Automatic coronary wall segmentation in intravascular ultrasound images using
      binary morphological reconstruction.
AB  - Intravascular ultrasound (IVUS) image segmentation can provide more detailed
      vessel and plaque information, resulting in better diagnostics, evaluation and
      therapy planning. A novel automatic segmentation proposal is described herein;
      the method relies on a binary morphological object reconstruction to segment the
      coronary wall in IVUS images. First, a preprocessing followed by a feature
      extraction block are performed, allowing for the desired information to be
      extracted. Afterward, binary versions of the desired objects are reconstructed,
      and their contours are extracted to segment the image. The effectiveness is
      demonstrated by segmenting 1300 images, in which the outcomes had a strong
      correlation to their corresponding gold standard. Moreover, the results were also
      corroborated statistically by having as high as 92.72% and 91.9% of true positive
      area fraction for the lumen and media adventitia border, respectively. In
      addition, this approach can be adapted easily and applied to other related
      modalities, such as intravascular optical coherence tomography and intravascular
      magnetic resonance imaging.

PMID- 21741158
TI  - Ultrasound studies on the shift of cervical tissues in different head and neck
      positions--impact on transoral endoscopic, minimally invasive and conventional
      thyroid surgery.
AB  - During the development of a transoral endoscopic, minimally invasive approach for
      thyroidectomy, the question arose as to how the distances of the submandibular
      gland (SG)-hyoid bone (HB)-thyroid gland (TG) change in differing head positions
      and how the TG itself changes shape. In a prospective, two-armed ultrasound study
      we studied 20 healthy volunteers each, all with no history of neck surgery or
      thyroid disease. Distances were measured in normal, reclined and "reclined with
      open mouth" positions. We found no remarkable differences and the distances were
      comparable with conventional open or minimally invasive thyroidectomy approaches.
      The TG lengthened significantly during reclination. This may result in a
      difficult preparation in the region of the suspensory ligament and may therefore
      increase the rate of postoperative vocal cord palsy caused by stretching of the
      recurrent laryngeal nerve. A supine flat position may minimize the risk of this
      postoperative complication of thyroidectomy.

PMID- 21741159
TI  - Current pathology keys of renal cell carcinoma.
AB  - CONTEXT: Renal cell carcinoma (RCC) in adults comprises a heterogeneous group of
      tumours with variable clinical outcomes that range from indolent to overtly
      malignant. The application of molecular genetic techniques to the study of renal
      neoplasms has resulted in an improved classification of these entities and a
      better understanding of the biologic mechanisms responsible for tumour
      development and progression. The current 2004 World Health Organisation
      classification of adult renal epithelial neoplasms has expanded rapidly with new
      categories recently incorporated. OBJECTIVE: To review and evaluate the evidence
      implicating pathologic features and classification of RCC in adults as a tool to
      approach patients' prognosis and modulate current therapy. EVIDENCE ACQUISITION:
      Members of Committee 3: Pathology, under the auspices of the International
      Consultation on Urological Diseases and the European Association of Urology (ICUD
      EAU) International Consultation on Kidney Cancer, performed a systematic review
      using PubMed. Participating pathologists discussed pathologic categories and
      diagnostic features of RCC in adults. EVIDENCE SYNTHESIS: We reviewed and
      discussed articles and the personal experiences of participating uropathologists.
      CONCLUSIONS: The conclusions reached by the ICUD-EAU 2010 International
      Consultation on Kidney Cancer emphasise the appropriate pathologic diagnosis of
      RCC in adults as a tool to approach patients' prognosis and modulate current
      therapy. Further emphasis should be placed on defining risk groups of RCC and
      diagnostic features of unusual tumours such as familial RCC, translocation RCC,
      and tubular mucinous and spindle cell carcinoma. A number of recently described
      entities and morphologic variants of classical categories deserves recognition
      because they can be important in differential diagnosis and therapy.

PMID- 21741160
TI  - Metastatic potential in renal cell carcinomas <=7 cm: Swedish Kidney Cancer
      Quality Register data.
AB  - BACKGROUND: Renal cell carcinoma (RCC) represents 2-3% of all malignancies and
      accounts for approximately 90% of all kidney malignancies. An increasing
      proportion of RCCs are discovered incidentally, and the average tumor diameter at
      diagnosis has decreased over the last few decades. Small RCCs have often been
      regarded by many as relatively harmless. OBJECTIVE: The objective was to evaluate
      the incidence of local T-category distribution and lymph node and distant
      metastases in relation to tumor size in RCCs <=7 cm in a nationally based patient
      population. DESIGN, SETTING, AND PARTICIPANTS: Data were extracted from the
      National Swedish Kidney Cancer Register containing 3489 RCCs diagnosed between
      2005 and 2008. This is a population-based registry including 99% of all RCCs
      diagnosed nationwide. The study included 2033 patients having a tumor <=7 cm in
      diameter. MEASUREMENTS: The size of the tumors was compared with sex, age, cause
      of diagnosis, Fuhrman grade, RCC type, and TNM category. RESULTS AND LIMITATIONS:
      Most RCCs were discovered incidentally and incidence correlated inversely to
      tumor size. There were 887 (43%) patients with category T1a tumors, 836 (40%)
      with category T1b, 174 (8%) with T3a, 131 (6%) with T3b/c, and 12 (1%) patients
      had invasion of adjacent organs (T4). A total of 309 (15%) patients had lymph
      node and/or distant metastases. Of the 177 1- to 2-cm RCCs, category T3 tumors
      were identified in three patients and lymph node and/or distant metastases were
      identified in 8 (5%). Only for tumors <=1 cm was there neither advanced stage nor
      metastasis. The occurrence of locally advanced growth, lymph node and distant
      metastases, and high tumor grade correlated to tumor size. Patients with Fuhrman
      grade III or IV had a four-fold greater risk of metastases than grades I or II.
      CONCLUSIONS: Lymph node and distant metastases occur even in small RCCs. Risk of
      metastases increases with tumor size. The data clearly show that small RCCs also
      have a malignant potential and should be properly evaluated and adequately
      treated.

PMID- 21741161
TI  - Familial clustering of sporadic kidney cancer: insufficient evidence to recommend
      routine screening in unaffected kin.

PMID- 21741162
TI  - Novel prognostic markers in the serum of patients with castration-resistant
      prostate cancer derived from quantitative analysis of the pten conditional
      knockout mouse proteome.
AB  - BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is associated
      with a poor outcome. Prognostic information is useful and aids treatment
      decisions. However, current nomograms based on clinical parameters alone have
      weak prognostic accuracy. Therefore, the identification of new prognostic serum
      biomarkers could be useful. OBJECTIVES: To assess if quantitative analysis of the
      phosphatase and tensin homolog (Pten) conditional knockout mouse proteome reveals
      significant prognostic biomarkers in mCRPC and to compare the accuracy of these
      biomarkers with known prognostic factors. DESIGN, SETTING, AND PARTICIPANTS:
      Fifty-seven patients with mCRPC were evaluated retrospectively. Prognostic
      factors used in clinical nomograms were assessed from the records. New candidate
      biomarkers in patients' sera were derived using a cancer genetics-guided model we
      recently described, screening the murine Pten-dependent glycoproteome.
      MEASUREMENTS: Quantification in patients' sera was performed by either mass
      spectrometry-based targeted proteomics or enzyme-linked immunosorbent assays.
      Prognostic biomarkers for survival were identified based on Kaplan-Meier models.
      In a second step, random forest analysis was performed to identify a prognostic
      signature combined from the pooled data of known predictors and newly identified
      biomarkers. RESULTS AND LIMITATIONS: With univariate analysis, 13 new significant
      prognostic factors for survival in the sera of mCRPC patients were found with a
      Bonferroni-corrected level of significance <5%. Random forest analysis revealed a
      five-factor predictor (thrombospondin 1; C-reactive protein; poliovirus receptor
      related 1; ephrin-A5; and membrane metallo-endopeptidase) with an accuracy of 96%
      and 94% for 12- and 24-mo survival, respectively. This means that, in our
      dataset, the error was reduced by 15% compared to using the Halabi et al.
      nomogram. The retrospective nature of the work and absence of a validating
      dataset is the major limitation of this work. CONCLUSIONS: Analysis of the serum
      proteome in mCRPC patients based on our Pten conditional knockout model, combined
      with known prognostic factors, potentially improves accuracy of prognostic
      nomograms. These newly identified markers have to be validated in prospective
      studies.

PMID- 21741163
TI  - Prognostic factors and predictive models in renal cell carcinoma: a contemporary
      review.
AB  - CONTEXT: The natural history of renal cell carcinoma (RCC) is highly
      unpredictable. Small renal masses may be accompanied by metastatic disease.
      Conversely, patients with locally advanced disease may enjoy long-term disease
      free survival. OBJECTIVE: To review the status of prognostic factors in RCC.
      EVIDENCE ACQUISITION: A literature review was performed using the PubMed,
      MEDLINE, and Cochrane databases for articles published as of February 15, 2010.
      Electronic articles published ahead of print were also considered. Search was
      limited to the English language. Search was conducted using the following
      keywords: renal cell carcinoma, molecular, tissue, markers, blood, urine,
      progression, prognosis, risk factor, and survival. Studies were selected
      according to the relevance of the study, the number of patients included,
      originality, actuality, and clinical applicability of the results. EVIDENCE
      SYNTHESIS: Four areas of prediction were examined: (1) new RCC diagnostics, (2)
      RCC grade and stage at diagnosis, (3) disease progression, and (4) disease
      specific mortality. All identified reports represented either case series or
      controlled studies. Although a large number of markers were identified, only a
      few were validated. Several prognostic factors were integrated in predictive or
      prognostic models. CONCLUSIONS: Several prognostic factors can help discriminate
      between favourable and unfavourable RCC phenotypes. Of those, several clinical,
      pathologic, and biologic markers have been tested and validated, and they are
      used in predictive and prognostic models. Nonetheless, the search continues,
      especially for informative markers predicting the response to targeted therapies.

PMID- 21741164
TI  - Temporal lobe pleomorphic xanthoastrocytoma and chronic epilepsy: long-term
      surgical outcomes.
AB  - OBJECTIVE: To review clinical features and surgical outcome in patients with
      temporal lobe pleomorphic xanthoastrocytomas (PXAs) and intractable epilepsy.
      METHODS: The Rush Surgical Epilepsy Database was queried to identify patients
      with chronic intractable epilepsy who underwent resection of a temporal lobe PXA
      at Rush University Medical Center. Medical records were reviewed for demographic,
      procedure and follow-up data. RESULTS: Four patients were identified with a
      temporal lobe PXA and intractable epilepsy. Average age of seizure onset was 16.5
      years and delay to surgery was 90 months. Complex partial seizures were the most
      common presenting symptom, shown in all 4 patients, and 3 of 4 patients presented
      with simple partial seizures as well. Seizures occurred with an average frequency
      of 4 per month (range 1-12 per month). Detailed operative and post-operative
      follow up data was available for all 4 patients. Gross total resection of the
      tumor was achieved in all 4 cases. Three of 4 cases had complete resection of the
      amygdala, and 3 cases had resections of the hippocampus (one partial and two
      complete). On histopathology, all tumors were found to be low-grade, without
      mitoses or necrosis. Average follow-up was 120 months (range 29-296 months) with
      all 4 patients achieving Engel's class I outcome. At last follow up, there was no
      radiographic or clinical evidence of tumor recurrence. There were no permanent
      complications. CONCLUSIONS: Temporal lobe pleomorphic xanthoastrocytomas causing
      chronic intractable epilepsy occur in younger patients, and demonstrate excellent
      long-term results in seizure improvement and tumor control with surgery. We
      support the choice between simple lesionectomy and a tailored resection with
      amygdalohippocampectomy guided by preoperative findings, intraoperative
      electrocorticography, and the severity and chronicity of the patient's epilepsy.

PMID- 21741165
TI  - PKC promotes the migration of colon cancer cells by regulating the
      internalization and recycling of integrin alphavbeta6.
AB  - Recently published studies have suggested that integrin trafficking is necessary
      to support cell migration, but the role of internalization and recycling of
      integrin alphavbeta6 in colon cancer cells remained unclear. In our study, we
      demonstrated the existence of the integrin cycle and found that inhibition of
      ERK2 phosphorylation by PD98059 or deletion of the ERK2 direct binding site on
      the beta6 cytoplasmic domain could interrupt the internalization of integrin
      alphavbeta6, but had no effect on its recycling. Furthermore, integrin
      alphavbeta6 trafficking played a key role in the migration of colon cancer cells
      towards fibronectin. Activation of PKC significantly accelerated the
      internalization and recycling of integrin alphavbeta6, which could facilitate
      rapid redistribution of integrin alphavbeta6 and increase cell motility. When
      colon cancer cells became crowded, the increase in alphavbeta6 levels at the cell
      surface was not accompanied by a change in total alphavbeta6 expression in cell
      lysates. This change may be due to a redistribution of alphavbeta6 in cell
      microstructures and a rapid cellular response towards the demands of migration.

PMID- 21741166
TI  - Suppression of invasion and metastasis of prostate cancer cells by overexpression
      of NDRG2 gene.
AB  - N-myc downstream regulated gene 2 (NDRG2) is involved in invasion and metastasis
      of cancer, furthermore it is frequently down-regulated in prostate cancer. Herein
      we evaluated the effect of NDRG2 overexpression on invasiveness and bone
      destruction in prostate cancer. The human prostate cancer cell line PC-3 and
      DU145 were infected with Ad-NDRG2 or Ad-LacZ. Overexpression of NDRG2 not only
      inhibited the growth of the cells, but also suppressed invasiveness of the cells
      in an in vitro assay. PC-3 cells infected with Ad-NDRG2 or Ad-LacZ were injected
      into the tibias of nude mice. Four weeks later, we found the mice injected with
      PC-3 cells overexpressing NDRG2 had smaller tumors and less bone destruction.
      These results demonstrate that NDRG2 overexpression can inhibit tumor growth and
      invasion, furthermore, it can decrease bone destruction caused by prostate cancer
      bone metastasis.

PMID- 21741167
TI  - Non-invasive monitoring of hepatocellular carcinoma in transgenic mouse with
      bioluminescent imaging.
AB  - A small animal imaging system for hepatocellular carcinoma (HCC)-specific
      reporter gene expression will enable monitoring of carcinogenesis or therapeutic
      intervention in vivo. Transgenic mouse was developed in which firefly luciferase
      (fLuc) expression was controlled by the AFP enhancer/promoter. The bioluminescent
      signals of the transgenic neonates were strong at their liver region and
      decreased after birth. Bioluminescent imaging (BLI) of a transgenic mouse treated
      with N-nitrosodiethylamine revealed distinct fLuc activity in the liver and an
      increased pattern with time. The transgenic mouse model can be used to monitor
      AFP producing HCC by a chemical carcinogen in a live animal by BLI.

PMID- 21741168
TI  - The effects of carbon sources and micronutrients in whey and fermented whey on
      the kinetics of phenanthrene biodegradation in diesel contaminated soil.
AB  - This paper demonstrates significant effects on phenanthrene degradation in diesel
      contaminated soil by the addition of organic amendments such as whey and
      fermented whey. Both amount of amendment added and mode of administration was
      shown to be decisive. There was a strong positive effect on the (14)C
      mineralization of phenanthrene by multiple (bi-weekly) additions of fermented
      whey 210 mg dw kg(-1) soil dw (FW multi) and also by single dose addition of 2100
      mg dw sweet whey kg(-1) soil dw (SW high). The most prominent effects on
      phenanthrene degradation kinetics were a five to fifteen fold increase in the
      linear growth term (k(2)) and a 23-27% increase in bioavailability factor S(0)
      for SW high and FW multi respectively. Also, total mineralization at the end of
      the experiment increased from 46% in the control to 66 and 71% respectively and
      the lag time was reduced from 21 to 15 days by multiple addition of fermented
      whey. The most significant stimulating effects on phenanthrene degradation
      kinetics could be attributed to lactate and vitamins. This study demonstrates a
      more complex dependence of carbon sources and growth factors for an aromatic
      compound such as phenanthrene in comparison to hexadecane.

PMID- 21741169
TI  - The acceleration of sludge granulation using the chlamydospores of Phanerochaete
      sp. HSD.
AB  - In the present paper, a novel method to accelerate sludge granulation is
      presented. Inoculation with chlamydospores of Phanerochaete sp. HSD accelerated
      sludge granulation during the treatment process of phenol wastewater, and the
      sludge granulation rate reached 66 +/- 2% on day 7, 32 days earlier than that of
      the control inoculated with activated sludge only. Aerobic granule in R1 (AG(R1))
      showed an annual ring-like multilayer structure and a primary core also existed
      in the nuclear area of the granule. The mechanism of rapid granulation revealed
      that the chlamydospore could survive in phenol wastewater and form the primary
      matrix on which aerobic granule was developed layer by layer. In addition, AG(R1)
      developed in a phenol uptake system to counteract the adverse effects of phenol
      inhibition. Higher tolerance toward wastewater with high phenol strength was
      exhibited, and the maximum specific phenol degradation rate reached 1.54 g phenol
      g(-1) VSS day(-1).

PMID- 21741170
TI  - Efficient removal of heavy metal ions from aqueous solution using salicylic acid
      type chelate adsorbent.
AB  - In this study, 5-aminosalicylic acid was successfully grafted onto the
      poly(glycidyl methacrylate) (PGMA) macromolecular chains of PGMA/SiO(2) to obtain
      a novel adsorbent designated as ASA-PGMA/SiO(2). The adsorption properties of ASA
      PGMA/SiO(2) for heavy metal ions were studied through batch and column methods.
      The experimental results showed that ASA-PGMA/SiO(2) possesses strong chelating
      adsorption ability for heavy metal ions, and its adsorption capacity for Cu(2+),
      Cd(2+), Zn(2+), and Pb(2+) reaches 0.42, 0.40, 0.35, and 0.31 mmol g(-1),
      respectively. In addition, pH has a great influence on the adsorption capacity in
      the studied pH range. The adsorption isotherm data greatly obey the Langmuir and
      Freundlich model. The desorption of metal ions from ASA-PGMA/SiO(2) is effective
      using 0.1 mol l(-1) of hydrochloric acid solution as eluent. Consecutive
      adsorption-desorption experiments showed that ASA-PGMA/SiO(2) could be reused
      almost without any loss in the adsorption capacity.

PMID- 21741171
TI  - Cloud point extraction for determination of lead in blood samples of children,
      using different ligands prior to analysis by flame atomic absorption
      spectrometry: a multivariate study.
AB  - The phase-separation phenomenon of non-ionic surfactants occurring in aqueous
      solution was used for the extraction of lead (Pb(2+)) from digested blood samples
      after simultaneous complexation with ammonium pyrrolidinedithiocarbamate (APDC)
      and diethyldithiocarbamate (DDTC) separately. The complexed analyte was
      quantitatively extracted with octylphenoxypolyethoxyethanol (Triton X-114). The
      multivariate strategy was applied to estimate the optimum values of experimental
      factors. Acidic ethanol was added to the surfactant-rich phase prior to its
      analysis by flame atomic absorption spectrometer (FAAS). The detection limit
      value of Pb(2+) for the preconcentration of 10 mL of acid digested blood sample
      was 1.14 MUg L(-1). The accuracy of the proposed methods was assessed by
      analyzing certified reference material (whole blood). Under the optimized
      conditions of both CPE methods, 10 mL of Pb(2+) standards (10 MUg L(-1))
      complexed with APDC and DDTC, permitted the enhancement factors of 56 and 42,
      respectively. The proposed method was used for determination of Pb(2+) in blood
      samples of children with kidney disorders and healthy controls.

PMID- 21741172
TI  - Performance evaluation of a continuous bipolar
      electrocoagulation/electrooxidation-electroflotation (ECEO-EF) reactor designed
      for simultaneous removal of ammonia and phosphate from wastewater effluent.
AB  - The present study aimed to evaluate the performance of a continuous bipolar ECEO
      EF reactor designed for simultaneous removal of ammonia and phosphate from
      wastewater effluent. The reactor was comprised of two distinct units:
      electrochemical and separation. In the electrochemical unit, Al, stainless steel,
      and RuO(2)/Ti plates were used. All the measurements were performed according to
      the standard methods. Maximum efficiency of the reactor for phosphate removal was
      99% at pH of 6, current density of 3A, detention time of 60 min, and influent
      phosphate concentration of 50mg/l. The corresponding value for ammonia removal
      was 99% at a pH of 7 under the same operational conditions as for phosphate
      removal. For both phosphate and ammonia, the removal efficiency was highest at
      neutral pH, with higher current densities, and with lower influent
      concentrations. In addition to removal of phosphate and ammonia, application of
      the Al(3+) plates enabled the removal of nitrite and nitrate, which may be
      present in wastewater effluent and are also products of the electrochemical
      process. The reactor was also able to decrease the concentrations of phosphate,
      ammonia, and COD under actual wastewater conditions by 98%, 98%, and 72%,
      respectively. According to the results of the present study, the reactor can be
      used for efficient removal of ammonia and phosphate from wastewater.

PMID- 21741173
TI  - Chemical interferences when using high gradient magnetic separation for phosphate
      removal: consequences for lake restoration.
AB  - A promising method for lake restoration is the treatment of lake inlets through
      the specific adsorption of phosphate (P) on strongly magnetizable particles (Fe)
      and their subsequent removal using in-flow high gradient magnetic separation
      (HGMS) techniques. In this work, we report an extensive investigation on the
      chemical interferences affecting P removal efficiencies in natural waters from 20
      Mediterranean ponds and reservoirs. A set of three treatments were considered
      based on different Fe particles/P concentration ratios. High P removal
      efficiencies (>80%) were found in freshwater lakes (conductivities<600 MU S cm(
      1)). However, a significant reduction in P removal was observed for extremely
      high mineralized waters. Correlation analysis showed that major cations (Mg(2+),
      Na(+) and K(+)) and anions (SO(4)(2-) and Cl(-)) played an essential role in P
      removal efficiency. Comparison between different treatments have shown that when
      increasing P and Fe concentrations at the same rate or when increasing Fe
      concentrations for a fixed P concentration, there exist systematic reductions in
      the slope of the regression lines relating P removal efficiency and the
      concentration of different chemical variables. These results evidence a general
      reduction in the chemical competition between P and other ions for adsorption
      sites on Fe particles. Additional analyses also revealed a reduction in water
      color, dissolved organic carbon (DOC) and reactive silicate (Si) concentrations
      with the addition of Fe microparticles.

PMID- 21741174
TI  - On the replacement of empirical parameters in multimedia mass balance models with
      QSPR data.
AB  - Official OECD recommendations give the highest priority to application of purely
      empirical phys/chem data (partition coefficients, environmental half-live times
      etc.) in multimedia mass balance modeling of environmental overall persistence
      and long-range transport for potentially hazardous chemicals. We have
      demonstrated that the replacement of the empirical data with those predicted by
      employing Quantitative Structure-Property Relationships (QSPR) technique did not
      significantly decrease the performance of The Tool 2.0--the OECD multimedia mass
      balance model. To prove this, we compared each other the output results (overall
      persistence -P(OV); characteristic traveling distance -CTD and transport
      efficiency TE) obtained from 6 of multimedia models. The models utilized
      combinations of experimentally determined and QSPR-predicted values of the
      partition coefficients and half-live times. For predicting phys/chem data, we
      utilized 2 QSPRs developed in our laboratory and the EPI Suite package (US EPA).
      We did not observe any statistically significant (p<0.05) differences between the
      models. This conclusion is important, because it leads to reducing time and costs
      of laboratory studies required during the risk assessment procedure. Moreover,
      regarding the obtained results, we proposed to replace the single-threshold
      approaches established by majority of international regulations to screen
      substances for persistence, bioaccumulation and long-range transport potential
      with the approaches taking into account uncertainty of the results and/or
      probability of passing a given threshold.

PMID- 21741175
TI  - A new in vitro test to evaluate the resistance level against acaricides of the
      cattle tick, Rhipicephalus (Boophilus) microplus.
AB  - In this article we present a new bioassay to assess the resistance status of
      ticks to acaricides. The Larval Tarsal Test (LTT) is a sensitive, highly time
      effective in vitro test. It allows the investigation of a large number of
      compounds and doses on the cattle tick Rhipicephalus (Boophilus) microplus in a
      short period of time. The ability of the LTT to assess the lethal concentration
      at 50% mortality (LC(50)) and resistance ratios (RRs) of a susceptible and a
      resistant R. microplus strain was compared with the FAO-recommended Larval Packet
      Test (LPT). Representative compounds of the carbamate, organophosphate (OP),
      synthetic pyrethroid (SP), formamidine (FOR), macrocyclic lactone and pyrazole
      classes were used for this comparison. The resistance status against OP, SP and
      FOR of the resistant R. microplus strain was confirmed in vivo. The LTT resulted
      in resistance ratios comparable to those obtained with the LPT. However, the
      lethal concentrations were up to 150-fold lower in the LTT than in the LPT. The
      advantage of the LTT is to simplify the methodology by avoiding the handling of
      larvae and using multi-well plates. The LTT is therefore a suitable test for the
      assessment of the level of resistance of R. microplus and is very promising to
      evaluate the resistance profile of field strains. Additionally, the LTT is also
      suitable to test other ixodid species.

PMID- 21741176
TI  - Propolis and amnion reepithelialise second-degree burns in rats.
AB  - Burns are serious consequences of trauma in terms of both imminent mortality and
      prolonged periods of morbidity. They are often accompanied by unsatisfactory
      cosmetic as well as functional and psychological outcomes. These complications
      emphasise the need for stronger efforts in achieving greater diversity and
      effectiveness in the treatment of skin burns. This study aimed to verify the
      effectiveness of gross and microscopic epidermal and dermal responses in the
      process of regenerative repair or healing of burns in rats that were treated
      either daily with 5% propolis ointment or by autologous amnion graft. Second
      degree burns were inflicted in the neck region of female rats by contact with a
      hot metal (at 130  degrees C) for 5 s. Propolis treatment accelerated the process
      of tissue repair and led to decreased local inflammation, which indicates that
      treatment with propolis was successful in the initial period (7 days) and
      stimulated the production of collagen fibre (assessed by morphometry) in all the
      periods evaluated (14 and 21 days). Amnion treatment inhibited local inflammation
      (assessed macroscopically), stimulated local epithelial regeneration (assessed
      microscopically) and stimulated the production of collagen fibre (assessed by
      morphometry) in the days following burn. These treatments offer new therapeutic
      strategies for treating severe skin burns; these strategies may allow the
      minimisation of scar formation, a more rapid return of function and, ultimately,
      a better quality of life for burn patients.

PMID- 21741177
TI  - Stress and animal models of inflammatory bowel disease--an update on the role of
      the hypothalamo-pituitary-adrenal axis.
AB  - Chronic psychosocial stress has been repeatedly shown in humans to be a risk
      factor for the development of several affective and somatic disorders, including
      inflammatory bowel diseases (IBD). There is also a large body of evidence from
      rodent studies indicating a link between stress and gastrointestinal dysfunction,
      resembling IBD in humans. Despite this knowledge, the detailed underlying
      neuroendocrine mechanisms are not sufficiently understood. This is due, in part,
      to a lack of appropriate animal models, as most commonly used rodent stress
      paradigms do not adequately resemble the human situation and/or do not cause the
      development of spontaneous colitis. Therefore, our knowledge regarding the link
      between stress and IBD is largely based on rodent models with low face and
      predictive validity, investigating the effects of unnatural stressors on
      chemically induced colitis. These studies have consistently reported that
      hypothalamo-pituitary-adrenal (HPA) axis activation during stressor exposure has
      an ameliorating effect on the severity of a chemically induced colitis. However,
      to show the biological importance of this finding, it needs to be replicated in
      animal models employing more clinically relevant stressors, themselves triggering
      the development of spontaneous colitis. Important in view of this, recent studies
      employing chronic/repeated psychosocial stressors were able to demonstrate that
      such stressors indeed cause the development of spontaneous colitis and, thus,
      represent promising tools to uncover the mechanisms underlying stress-induced
      development of IBD. Interestingly, in these models the development of spontaneous
      colitis was paralleled by decreased anti-inflammatory glucocorticoid (GC)
      signaling, whereas adrenalectomy (ADX) prior to stressor exposure prevented its
      development. These findings suggest a more complex role of the HPA axis in the
      development of spontaneous colitis. In the present review I summarize the
      available human and rodent data in order to provide a comprehensive understanding
      of the biphasic role of the HPA axis and/or the GC signaling during stressor
      exposure in terms of spontaneous colitis development.

PMID- 21741178
TI  - The Desire Thinking Questionnaire: development and psychometric properties.
AB  - Desire thinking is a voluntary cognitive process involving verbal and imaginal
      elaboration of a desired target. Recent research has highlighted the role of
      desire thinking in the maintenance of addictive, eating and impulse control
      disorders. The goal of this research project was to develop the first self-report
      measure of desire thinking. In Study 1 we constructed the Desire Thinking
      Questionnaire (DTQ) and conducted a preliminary factor analysis which identified
      two factors. The first factor concerned the perseveration of verbal thoughts
      about desire-related content and experience and was named 'Verbal Perseveration'.
      The second factor concerned the tendency to prefigure images about desire-related
      content and experience and was named 'Imaginal Prefiguration'. In Study 2 we
      performed a confirmatory factor analysis which provided support for this two
      factor solution, with both factors achieving adequate internal consistency.
      Divergent validity was also established through correlation analyses. In Study 3
      the temporal stability of the DTQ was examined and confirmed. Finally, in Study
      4, the predictive validity of the DTQ in a sample of alcohol abusers was
      investigated. The DTQ was shown to possess good psychometric properties, as well
      as divergent and predictive validity. This self-report measure may aid future
      research into desire thinking and craving, as well as facilitate assessment and
      case formulation within the context of addictive, eating and impulse control
      disorders.

PMID- 21741179
TI  - Behavioural alteration in chronic pain: are brain glia involved?
AB  - Behavioural symptoms such as abnormal emotionality (including anxious and
      depressive episodes) and cognition (for instance weakened decision-making) are
      highly frequent in both chronic pain patients and their animal models. The theory
      developed in the present article posits that alterations in glial cells
      (astrocytes and microglia) in cortical and limbic brain regions might be the
      origin of such emotional and cognitive chronic pain-associated impairments.
      Indeed, in mood disorders (unipolar depression, anxiety disorders, autism or
      schizophrenia) glial changes in brain regions involved in mood control
      (prefrontal and cingulate cortices, amygdala and the hippocampus) have been
      recurrently described. Besides, glial cells have been undoubtedly identified as
      key actors in the sensory component of chronic pain, owing to the profound
      phenotypical changes they undergo throughout the sensory pathway. Hence, the
      possibility arises that brain astrocytes and microglia react in upper brain
      structures as well, mediating the related mood and cognitive dysfunctions in
      chronic pain. So far, only very few studies have provided results in this
      prospect, mainly indirectly in pain-independent researches. Nevertheless, the
      first scant available data seem to merge in a unified description of a brain
      glial reaction occurring after chronic peripheral lesion. The present article
      uses this scarce literature to formulate the provocative theory of a glia-driven
      mood and cognitive dysfunction in chronic pain, expounding upon its validity and
      putative therapeutical impact as well as its current limitations and expected
      future developments.

PMID- 21741180
TI  - Reconstitution of the human biome as the most reasonable solution for epidemics
      of allergic and autoimmune diseases.
AB  - A wide range of hyperimmune-associated diseases plague post-industrial society,
      with a prevalence and impact that is staggering. Strong evidence points towards a
      loss of helminths from the ecosystem of the human body (the human biome) as the
      most important factor in this epidemic. Helminths, intestinal worms which are
      largely eradicated by elements of post-industrial culture including toilets and
      water treatment facilities, have an otherwise ubiquitous presence in vertebrates,
      and have co-evolved with the immune system. Not only do helminths discourage
      allergic and autoimmune reactions by diverting the immune system away from these
      pathologic processes and stimulating host regulatory networks, helminths release
      a variety of factors which down-modulate the immune system. A comprehensive view
      of hyperimmune-related disease based on studies in immunology, parasitology,
      evolutionary biology, epidemiology, and neurobiology indicates that the effects
      of biome depletion may not yet be fully realized, and may have an unexpectedly
      broad impact on many areas of human biology, including cognition. Fortunately,
      colonization with helminths results in a cure of numerous autoimmune and allergic
      diseases in laboratory rodents, and clinical studies in humans have indicated
      their utility for treatment of both multiple sclerosis and inflammatory bowel
      disease. Based on these considerations, commitment of considerable resources
      toward understanding the effects of "biome depletion" and systematically
      evaluating the most effective approach toward biome reconstitution is strongly
      encouraged.

PMID- 21741181
TI  - Recommendations for insulin initiation based on ethnicity.
AB  - Even in a developed country like USA, substantial number of subjects with type 2
      diabetes fail to achieve adequate glycemic control despite the availability of
      several groups of anti-diabetic medications targeting multiple pathophysiological
      features of type 2 diabetes. Are we treating our type 2 diabetes subjects
      appropriately? To aid practicing clinicians various professional bodies like
      American Diabetes Association (ADA), European Association for Study of Diabetes
      (EASD), Canadian Diabetes Association (CDA), etc. regularly publish clinical
      practice guidelines and consensus statements. Since racial and ethnic differences
      in insulin resistance, dietary pattern, glucose metabolism, genetic variation are
      known phenomena, it would be interesting to evaluate the aptness of these
      guidelines from ethnopharmacy perspective. We postulate that certain ethnic
      characteristics of populations will decide the best form of insulin therapy
      rather than blanket recommendations on starting every patient on basal insulin.

PMID- 21741182
TI  - Impact of chromosome 17 centromere region assessment on HER2 status reported in
      breast cancer.
AB  - Recent studies have indicated that polysomy 17 is a rare event in breast cancer,
      and polysomy is usually mimicked in FISH analysis by gain or amplification of the
      centromere covered by the chromosome 17 centromere probe. To estimate the impact
      of chromosome 17 centromere assessment on routine practice, we conducted a
      retrospective re-classification study. Four hundred and five consecutive cases
      were selected. The original molecular pathology reports were available.
      Centromere 17 copy counts were ignored in the reassessment. Altogether, nineteen
      (4.69%) discrepant cases were found, from which five (1.23%) were considered
      originally non-amplified but had an HER2 copy number >6. Therefore, we
      reclassified them as HER2-amplified, while fourteen (3.46%) cases were originally
      considered amplified with 6 or fewer HER2 signals/cell. The discrepant cases
      found in our reassessment study would require further high-resolution genetic
      analysis to resolve the disagreement. On the other hand, our result also
      highlights that for the vast majority of breast cancer cases traditional FISH
      examination is still adequate to reach the correct diagnosis. This diagnostic gap
      must be filled by more sophisticated genetic examinations. Moreover, upcoming
      HER2 guidelines should consider the aid that high-resolution karyotyping can give
      to the diagnostic algorithm.

PMID- 21741183
TI  - A novel method to incorporate the spatial location of the lung dose distribution
      into predictive radiation pneumonitis modeling.
AB  - PURPOSE: Studies have proposed that patients who receive radiation therapy to the
      base of the lung are more susceptible to radiation pneumonitis than patients who
      receive therapy to the apex of the lung. The primary purpose of the present study
      was to develop a novel method to incorporate the lung dose spatial information
      into a predictive radiation pneumonitis model. A secondary goal was to apply the
      method to a 547 lung cancer patient database to determine whether including the
      spatial information could improve the fit of our model. METHODS AND MATERIALS:
      The three-dimensional dose distribution of each patient was mapped onto one
      common coordinate system. The boundaries of the coordinate system were defined by
      the extreme points of each individual patient lung. Once all dose distributions
      were mapped onto the common coordinate system, the spatial information was
      incorporated into a Lyman-Kutcher-Burman predictive radiation pneumonitis model.
      Specifically, the lung dose voxels were weighted using a user-defined spatial
      weighting matrix. We investigated spatial weighting matrices that linearly scaled
      each dose voxel according to the following orientations: superior-inferior,
      anterior-posterior, medial-lateral, left-right, and radial. The model parameters
      were fit to our patient cohort with the endpoint of severe radiation pneumonitis.
      The spatial dose model was compared against a conventional dose-volume model to
      determine whether adding a spatial component improved the fit of the model.
      RESULTS: Of the 547 patients analyzed, 111 (20.3%) experienced severe radiation
      pneumonitis. Adding in a spatial parameter did not significantly increase the
      accuracy of the model for any of the weighting schemes. CONCLUSIONS: A novel
      method was developed to investigate the relationship between the location of the
      deposited lung dose and pneumonitis rate. The method was applied to a patient
      database, and we found that for our patient cohort, the spatial location does not
      influence the risk of pneumonitis.

PMID- 21741184
TI  - [Detection of enteroviruses in urban wastewater in Yopougon, Abidjan].
AB  - AIM: The aim of this study was to determine prevalence of enteroviruses in raw
      municipal wastewater and specify serotypes circulating. METHODS: After virus
      concentration by WHO recommend method, aqueous phase of 68 samples was inoculate
      on BGM, RD, L20B and Hep2 cells lines. Typing after titration was performed by
      microplate neutralization test with specific horse immune serum against EV (kit
      RIVM/WHO). NPEV strains were confirmed by RT-PCR test in 5'NC genomic region.
      Antigenic and molecular tests of Polioviruses intratypic differentiation were
      performed to determine vaccine or wild origin of Poliovirus strains. RESULTS:
      Viral isolation obtained 43/68 (65.15 %) positives samples. Among these 35/43
      (81. 39%) were EV and 8/43 (19.04 %) non EV strain. Among EVs, 34/35 (97.14 %)
      were NEPV and 2/35 (5.71 %) vaccinal Poliovirus strains type 2 (Sabin-like). NEPV
      typing gave 77 % untypeable strains by conventionally method. The average virus
      concentration estimated in the raw sewage is 4.28*10(5) PFU/L. CONCLUSION:
      Various contacts between people and these waters expose them to health risks.

PMID- 21741185
TI  - Genetic characterization of H7N2 influenza virus isolated from pigs.
AB  - Because pigs have respiratory epitheliums which express both alpha2-3 and alpha2
      6 linked sialic acid as receptors to influenza A viruses, they are regarded as
      mixing vessel for the generation of pandemic influenza viruses through genetic
      reassortment. A H7N2 influenza virus (A/swine/KU/16/2001) was isolated from pig
      lungs collected from the slaughterhouse. All eight genes of the influenza virus
      were sequenced and phylogenetic analysis indicated that A/swine/KU/16/2001
      originated in Hong Kong and genetic reassortment had occurred between the avian
      H7N2 and H5N3 influenza viruses. The first isolation of H7 influenza virus in
      pigs provides the opportunity for genetic reassortment of influenza viruses with
      pandemic potential and emphasizes the importance of surveillance for atypical
      swine influenza viruses.

PMID- 21741186
TI  - Vertebral fractures in women aged 50 years and older with clinical risk factors
      for fractures in primary care.
AB  - BACKGROUND: The identification of vertebral fractures (VFs) is important for
      decisions on fracture prevention. Vertebral fracture assessment (VFA) was shown
      to be a patient-friendly and valid method for detecting undiagnosed VFs in
      (Dutch) women. However, this has only been investigated in women seeking care at
      secondary or tertiary institutions. OBJECTIVE: To investigate the prevalence of
      previously undiagnosed VFs in women in Dutch primary care using VFA. STUDY
      DESIGN: A total of 566 Dutch women aged 50 years and older (mean age, 69 years;
      SD=8.4) with clinical risk factors (CRFs) for fractures volunteered for dual
      energy X-ray absorptiometry (DXA) measurement and VFA. VFs were defined semi
      quantitatively using Genant's method. RESULTS: One CRF was present in each of 130
      women, 274 had two, and 162 women had more than two CRFs. In 120 (21%) of the
      women, previously unknown osteoporosis (T-score <= -2.5SD) was diagnosed, and in
      174 (31%), a previously undiagnosed moderate or severe VF was found. No
      osteoporosis was found in 130 (75%) of the women with a VF. Based on the outcome
      of DXA, 21% of the women were eligible for treatment, while the combination of
      DXA and VFA resulted in a total of 250 (44%) women requiring treatment.
      CONCLUSIONS: The percentage of previously unknown VFs diagnosed by VFA in women
      aged 50 years and older with one or more CRFs for fractures in primary care is
      high. When only using BMD measurements, only half the women eligible for
      treatment would actually receive this. We recommend performing VFA in all women
      aged 50 years and older who are referred for DXA based on Dutch case finding
      criteria.

PMID- 21741187
TI  - D-dimer assays for the identification of menstrual blood.
AB  - A method to reliably distinguish menstrual blood from blood in the normal
      circulation (peripheral blood) would be of considerable use in the forensic
      analysis and interpretation of evidence in sexual offence investigations.
      Previous attempts to address this issue have explored microscopy, lactate
      dehydrogenase isozyme identification, mRNA and miRNA profiling, and
      identification of the products of fibrinolysis. Here, four assays for D-dimer, a
      terminal degradation product of fibrinolysis, are evaluated for their specificity
      and sensitivity in detection of menstrual blood. In addition the effect of
      exercise, and sample storage upon D-dimer detection was investigated. Comparison
      of different assays revealed significant differences in results given.
      Nevertheless, no positive results for D-dimer were obtained using peripheral
      blood, mixtures of peripheral blood with semen, or peripheral blood taken from
      donors after moderate exercise. D-dimer was found to be detectable in 100% of
      menstrual blood samples after 1 week at room temperature and also in samples
      stored long-term (>3 years) at -20  degrees C. D-dimer may be an effective,
      simple to use tool for the presumptive identification of menstrual blood
      identification.

PMID- 21741188
TI  - Involvement of the health industry in the fight against doping in sport.
AB  - Most substances used for doping in sport are legitimate pharmaceutical products
      deviated from their intended therapeutic applications. One of the major
      challenges for anti-doping authorities, in anticipation of future doping trends,
      is to assess the doping potential of drugs in development by the health industry
      and to timely develop anti-doping analytical methods to detect their abuse before
      such drugs become available to athletes intending to use them as doping agents.
      In this regard, the World Anti-Doping Agency (WADA) has recently consolidated
      several agreements with representatives from the pharmaceutical sector in order
      to establish a framework of collaboration and to facilitate the identification
      and transfer of information on drugs in development. The context of the
      collaborative effort between WADA and the pharmaceutical and biotechnology
      industries, as well as the role of drug regulatory agencies in an integrated
      process in support of the fight against doping in sport are described in this
      article.

PMID- 21741189
TI  - Initial study of arthropods succession and pig carrion decomposition in two
      freshwater ecosystems in the Colombian Andes.
AB  - Entomological succession and trophic roles of arthropods associated with
      different stages of carcass decomposition were studied to estimate the post
      mortem submersion interval in two freshwater ecosystems in the Colombian Andes,
      at an altitude of 2614 m. Pig carcasses were employed as models placed 68 m
      apart, one in a stream (lotic) and another in an artificial lake (lentic).
      Decomposition time to skeletal remains was 74 days in the lake and 80 days in the
      stream. Six phases of decomposition were established: submerged fresh, early
      floating, floating decay, bloated deterioration, floating remains and sunken
      remains. A total of 18,832 organisms associated with the carcasses were
      collected: 11,487 in the lake (four orders, 19 families and 33 species) and 7345
      in the stream (eight orders, 15 families and 25 species). Organisms were
      classified in the following ecological categories: shredders, collectors,
      predators, necrophagous, sarcosaprophagous and opportunists. Physical and
      chemical properties of the habitats, such as water temperature, CO(2) and
      conductivity, varied according to rainfall. In the lake, shredders (Coleoptera:
      Tropisternus sp. and Berosus sp.) and collectors (Diptera: Chironomus sp.) were
      found to be associated with submerged phases. Predators (Odonata) were only
      present during the first phases. Coleoptera (Dytiscidae) were found during
      floating decay and bloated deterioration stages. In the stream, shredders
      (Hyalella sp.) and collectors (Simulium sp.) were found during all stages,
      whereas the predator Oxelytrum discicolle was found exclusively during the
      floating stages, during which body temperature increased in a fashion similar to
      active decay in terrestrial environments.

PMID- 21741190
TI  - Use of amplitude-integrated electroencephalography (aEEG) and near infrared
      spectroscopy findings in neonates with asphyxia during selective head cooling.
AB  - BACKGROUND: Amplitude-integrated electroencephalogram (aEEG) at <6 h is the best
      single outcome predictor in term infants with perinatal asphyxia at normothermia.
      Hypothermia treatment has changed the cutoff values for outcome prediction by
      using time at onset of normal trace and SWC. Cerebral hemodynamics and
      oxygenation changes detected by near infrared spectroscopy (NIRS) during
      hypothermia treatment in aphyxiated neonates are not a well known issue. AIM: The
      aim of this study was to investigate the correlations between brain monitoring
      (amplitude integrated EEG and NIRS) and outcome in asphyxiated full-term infants
      with moderate/severe hypoxic-ischemic encephalopathy before, during and after
      hypothermia treatment. METHOD: Ten neonates were recruited for hypothermia
      treatment by using the cool cap entry criteria. aEEG and NIRS were applied in 10
      and 8 patients, respectively with moderate and severe hypoxic-ischemic
      encephalopathy before, just after brain cooling and rewarming periods. Patterns
      and voltages of aEEG backgrounds sleep-wake cycles (SWC) and NIRS values (TOI%
      and FTOE) were recorded. During the follow up their outcomes were assessed by
      using the Bayley Scales of Infant Development II. CONCLUSION: Hypothermia changes
      the predictive value of early aEEG. Normalization of a baby's aEEG and the
      appearance of SWCs while being cooled occurs later. In our study one patient had
      normal aEEG background pattern at 80 and imminent SWC at 90 h after birth and
      still had normal Bayley scores at 24 months. Time to normal aEEG and SWC
      appearance should be carefully evaluated during the cooling period. NIRS values
      were different due to the clinical presentations of the patients.

PMID- 21741191
TI  - Atretic parietal cephalocele associated with sinus pericranii: embryological
      consideration.
AB  - We report a case of atretic parietal cephalocele with a persistent parietal
      falcine sinus and partial absence of the straight sinus. The direct puncture
      angiographic study demonstrated that there was a major venous channel through the
      parietal skull defect. From the embryological point of view, this association may
      provide us with possible pathoetiologic evidence of congenital sinus pericranii
      is one of the alternative venous drainage pathways to compensate venous outflow
      in the cases of intracranial developmental anomalies.

PMID- 21741192
TI  - Magnetic resonance imaging of the lumbar spine with axial loading: a review of
      120 cases.
AB  - PURPOSE: To evaluate the imaging findings of patients with clinical symptoms of
      lower back pain who underwent magnetic resonance imaging (MRI) of the lumbar
      spine with axial loading. MATERIALS AND METHODS: We examined 120 patients by MRI,
      before and after axial loading, using a compression device that applied 50% of
      their body weight for a load time of 5min. The dural sac cross area (DSCA) was
      examined by two experienced radiologists before and after axial load, and their
      findings were compared. Degenerative abnormalities within and adjacent to the
      spinal canal were also analyzed. RESULTS: A reduction in DSCA greater than
      15mm(2) after axial load was defined as significant, and was found in 81 patients
      (67.5%) and 138 disc spaces (38.3%). Reduction was most frequent at L4-L5 (n=55).
      For other disorders, a 9% increase in cases of bulging disc was seen during axial
      loading, and seven disc spaces showed protrusion/extrusion only after load. Facet
      joint synovial cysts, foraminal stenosis, and hypertrophy of the flavum ligaments
      showed almost no differences, pre- and post-load. CONCLUSION: For adequate
      evaluation of lumbar symptoms, examination should be performed with axial
      loading, especially in cases of suspected spinal stenosis.

PMID- 21741193
TI  - WITHDRAWN: Stability of cerebral activation patterns in patients with first
      episode schizophrenia and a healthy control group using functional MRI.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21741194
TI  - Promoting advance care planning as health behavior change: development of scales
      to assess Decisional Balance, Medical and Religious Beliefs, and Processes of
      Change.
AB  - OBJECTIVE: To develop measures representing key constructs of the
      Transtheoretical Model (TTM) of behavior change as applied to advance care
      planning (ACP) and to examine whether associations between these measures
      replicate the relationships posited by the TTM. METHODS: Sequential scale
      development techniques were used to develop measures for Decisional Balance (Pros
      and Cons of behavior change), ACP Values/Beliefs (religious beliefs and medical
      misconceptions serving as barriers to participation), Processes of Change
      (behavioral and cognitive processes used to foster participation) based on
      responses of 304 persons age>=65 years. RESULTS: Items for each scale/subscale
      demonstrated high factor loading (>.5) and good to excellent internal consistency
      (Cronbach alpha .76-.93). Results of MANOVA examining scores on the Pros, Cons,
      ACP Values/Beliefs, and POC subscales by stage of change for each of the six
      behaviors were significant, Wilks'lambda=.555-.809, eta(2)=.068-.178, p<=.001 for
      all models. CONCLUSION: Core constructs of the TTM as applied to ACP can be
      measured with high reliability and validity. PRACTICE IMPLICATIONS: Cross
      sectional relationships between these constructs and stage of behavior change
      support the use of TTM-tailored interventions to change perceptions of the Pros
      and Cons of participation in ACP and promote the use of certain Processes of
      Change in order to promote older persons' engagement in ACP.

PMID- 21741195
TI  - Implementing patient question-prompt lists into routine cancer care.
AB  - OBJECTIVE: To examine the feasibility and acceptability of routine provision of
      patient question prompt lists (QPLs) to promote patient participation and patient
      clinician communication in medical consultations. METHODS: Four cancer centres
      across NSW, Australia (two rural, two urban) were invited to participate,
      involving distribution of QPLs to patients seeing a medical or radiation
      oncologist, or palliative care clinician. Patients rated their satisfaction after
      their next consultation. Cancer specialists provided their views at the end of
      the study. RESULTS: Sixty-four percent (389/606) of patients attending
      consultations received a QPL. Of patients offered a QPL (426), 91% accepted. Of
      139 patients surveyed post-consultation, 89% reported reading the QPL and, of
      these, 44% referred to the QPL during the consultation at least once. All of 10
      cancer specialists providing their views post-implementation reported that QPL
      implementation in routine practice was feasible and did not strain resources.
      CONCLUSIONS: Cancer patients and cancer specialists showed support for routine
      dissemination of the QPL. PRACTICE IMPLICATIONS: For successful implementation of
      evidence-based tools we recommend promotion by local clinical champions,
      negotiation with clinic staff about dissemination methods, raised patient
      awareness through on-site project facilitators, media, consumer and support
      groups, and availability of resources in hard copy and via online sources.

PMID- 21741196
TI  - I want to have a healthy life.

PMID- 21741197
TI  - Changes in methadone maintenance therapy during and after pregnancy.
AB  - OBJECTIVE: The aim of this study is to better understand anticipated changes in
      daily methadone doses as a guide for prescription during pregnancy. METHODS: This
      retrospective case series involved a single cohort longitudinal design of 139
      consecutively chosen women who began methadone therapy before 26 completed
      gestational weeks. Changes in the single daily dose were based on a standard
      opiate withdrawal scale and determined from early pregnancy until 6 weeks
      postpartum. RESULTS: As gestation advanced, the methadone dose increased (86%)
      rather than remained the same (8%) or decreased (7%). This gradual increase in
      daily dose during pregnancy (mean increase = 24 mg, 95% confidence level = 20-28
      mg) was statistically significant (p < .001) regardless of the initial
      maintenance dose. By the sixth postpartum week, most subjects (85%) took within
      10 mg of their dose at delivery (mean change in dose = -4 mg, 95% confidence
      interval = -6 to -2 mg). CONCLUSIONS: Daily doses of methadone increased until
      the third trimester, then remained essentially unchanged through the sixth
      postpartum week.

PMID- 21741199
TI  - Predictors of clinical outcomes of resected ampullary adenocarcinoma: a single
      institution experience.
AB  - BACKGROUND: In the absence of prospective data, the use of adjuvant therapy in
      ampullary adenocarcinoma is contingent upon the clinicopathological features
      which can correlate to 5-year post-operative survival and disease relapse.
      METHODS: We investigated the factors associated with clinical outcomes among 72
      patients who underwent pancreatoduodenectomy at the Cleveland Clinic from 1995 to
      2007 for histologically confirmed adenocarcinoma of the ampulla of Vater.
      RESULTS: R0 resection was achieved in 96% of patients (median age, 72 years; 58%
      males, 89% Caucasians). Nineteen patients experienced disease relapse after
      surgery and 61% were alive within 5 years of follow up. Thirty five percent of
      patients received some form of adjuvant therapy. Perineural tumor invasion (p <
      0.01) and presence of ulcerated tumor on histopathology (p < 0.01) were
      associated with higher rates of tumor relapse and poor 5-year overall survival in
      multivariable analysis. Lymph node involvement (p = 0.02) also portended poor
      overall survival after adjustment for other covariates. Although adjuvant therapy
      was associated with poor clinical outcomes in univariate analysis, it
      demonstrated a favorable albeit non-significant trend in multivariable analysis.
      CONCLUSIONS: Factors associated with poor clinical outcomes in this contemporary
      single-institution study, included perineural invasion, tumor ulceration, and
      lymph node involvement. No definite conclusion could be made in regards to
      adjuvant treatment.

PMID- 21741198
TI  - Delay discounting, impulsiveness, and addiction severity in opioid-dependent
      patients.
AB  - Individuals who abuse drugs show higher delay discounting (DD) rate and
      impulsiveness scores compared with controls; however, it is unclear if DD rate
      covaries with severity of the addiction or if an individual's discounting rate
      can be changed by effective substance abuse treatment. This study compared
      methadone maintenance treatment (MMT) patients (n = 30) who had not used illegal
      drugs for 2 years with drug-using MMT patients (n = 30) and controls (n = 25) in
      terms of addiction severity, DD rate, and impulsiveness. Methadone patients
      abstinent from illegal drugs scored significantly lower on a number of addiction
      severity measures than the drug-using methadone patients. In addition, both
      groups of MMT patients showed significantly higher rates of DD and impulsiveness
      than the control group; however, no differences in DD rate or impulsiveness were
      found between the groups of patients. Results suggest that DD rate and
      impulsiveness may not covary with indicators of addiction severity in MMT
      patients.

PMID- 21741200
TI  - [Clinical evaluation of post-surgical bleeding after a sugammadex injection].
AB  - OBJECTIVE: Sugammadex reverses neuromuscular blockade by chemical encapsulation
      of nondepolarizing neuromuscular blocking drugs (rocuronium and vecuronium). The
      imprint of this new molecule has recently been supplemented with a section on
      haemostasis notifying a longer clotting time without documented clinical
      consequences. This has resulted in recommendations on the use of sugammadex in
      the presence of coagulation disorders (pharmacologically-induced or not). The
      objective of this study was to analyze the experience gathered with this molecule
      on clinically-evaluated bleeding. No study on this subject is currently
      available. METHODS: This is a retrospective study over 1 year between August 2009
      and August 2010. All patients with laparotomies for cancer surgery requiring
      suction drains were included. Patients were allocated to groups according to the
      type of reversal (without sugammadex versus sugammadex 2 or 4 mg/kg). The
      endpoint was clinically-evaluated postoperative bleeding (reoperation for
      haemostasis, blood-stained laparotomy dressings in the post-anaesthesia care unit
      [PACU], cumulative volume collected in suction drains upon arrival in PACU and
      then after 2 hours and the next morning at 6a.m). RESULTS: One hundred and ninety
      three patients were included in three groups, 78 in the group "without
      sugammadex", 95 in "sugammadex 2mg/kg" and 20 in "sugammadex 4 mg/kg". There were
      no reoperations for haemostasis. The comparison among different groups for the
      endpoint of bleeding showed no significant difference. CONCLUSION: In this
      retrospective study performed in patients at high risk of postoperative bleeding,
      sugammadex at doses of 2 and 4 mg/kg was not associated with increased bleeding.
      This study, the first in this field, suggests that future prospective
      investigations should target patients receiving 4 or 16 mg/kg of sugammadex
      and/or with documented preoperative abnormal coagulations tests.

PMID- 21741201
TI  - Subcellular proteomics: determination of specific location and expression levels
      of lymphatic metastasis associated proteins in hepatocellular carcinoma by
      subcellular fractionation.
AB  - BACKGROUND: Subcellular fractionation and proteomics form an ideal partnership
      when it comes to specific location and analysis of intracellular organelles and
      expression levels of multiprotein complexes. Lymphatic metastasis is the major
      complicated system involving multiple factors. However, to date lymphatic
      metastatic mechanism is poorly understood. AIM: To specifically locate expression
      site by subcellular fractionation, based on expression levels, interpret the
      involvement of different lymphatic metastasis associated proteins in
      hepatocellular carcinoma cell lines with different lymphatic metastasis
      potential. METHOD: Mouse hepatocellular cell lines Hca-F and Hca-P are used to
      evaluate the location and expression levels of some lymphatic metastasis
      associated proteins in the cell by using subcellular fractionation kit and
      Western blot analysis. The proteins under studies were Gelsolin, JNK and Annexin
      7. RESULTS: Gelsolin was sequestered in cytoplasm, membrane and cytoskeleton in F
      cells but in P-cells, it was found in cytoplasm and cytoskeleton .JNK was located
      in nuclear fraction and cytoskeleton in F and P cells, Annexin7 was in cytoplasm
      with its two isoforms only at this location, cell membrane and cytoskeleton in F
      and P cells. With the high expression level of Gelsolin, JNK and Annexin 7 in Hca
      F cell line than Hca-P cell line. CONCLUSION: With subcellular fractionation
      specific location of Gelsolin, JNK and Annexin 7 at various cell sites during
      lymphatic metastasis were determined. High expression levels were found in high
      lymphatic metastasis potential cell lines which indicate their roles according to
      different expression sites in the disease.

PMID- 21741202
TI  - Antitumor cell activity in vitro by myristoylated-peptide.
AB  - New anticancer drugs are needed to support cancer treatment. Cancer involves the
      uncontrolled proliferation of tumor cells, and many anticancer drugs are agents
      that inhibit tumor cell growth. The antitumor cell N-myristoylated-peptide is a
      natural product purified from Heliothis virescens insect hemolymph with
      essentially no cytotoxicity against human foreskin fibroblast cells. A
      synthesized structure of six amino acids (Myristoyl-Cys-Ala-Val-Ala-Tyr-[3
      methyl]His-OMe; M.W. 902.2 Da) was screened at 10 MUM for in vitro antitumor
      activity against 56 human tumor cell lines by the National Cancer Institute
      (NCI). The NCI found that 34 of the 56 tumor cell lines (representing eight major
      tumor types) were sensitive (> 50% growth inhibition of tumor cells) to the
      myristoylated-peptide. The best overall antitumor activities (>60% average growth
      inhibition) were seen against 17 tumor cell lines for non-small cell lung cancer,
      leukemia and melanoma and for eight other tumor cell lines. The NCI finds that
      their in vitro screen is an effective selector of compounds with in vivo
      antitumor activity.

PMID- 21741203
TI  - Rejection sensitivity mediates the relationship between social anxiety and body
      dysmorphic concerns.
AB  - The goal of this study was to examine the role of rejection sensitivity in the
      relationship between social anxiety and body dysmorphic concerns. To test our
      hypothesis that rejection sensitivity mediates the link between social anxiety
      and body dysmorphic concerns, we administered self-report questionnaires to 209
      student volunteers. Consistent with our prediction, rejection sensitivity
      partially mediated the relationship between social anxiety symptoms and body
      dysmorphic concerns. The implications of the overlap between these constructs are
      discussed.

PMID- 21741205
TI  - A location-based prompting system to transition autonomously through vocational
      tasks for individuals with cognitive impairments.
AB  - This study assessed the possibility of training two individuals with cognitive
      impairments using location-based task prompting system in a supported employment
      program. This study was carried out according to an ABAB sequence in which A
      represented the baseline and B represented intervention phases. Data showed that
      the two participants significantly increased their target response, thus
      improving vocational job performance during the intervention phases. Practical
      and developmental implications of the findings are discussed.

PMID- 21741206
TI  - Peer with intellectual disabilities as a mindfulness-based anger and aggression
      management therapist.
AB  - A young man with intellectual disabilities (ID) and mental illness, who had
      previously been taught to successfully manage his aggressive behavior by using
      Meditation on the Soles of the Feet, reported that he shared his mindfulness
      practice with his peers with ID. When requested by his peers, and without any
      training as a therapist, he began to teach this procedure to his peers for
      controlling their anger and aggressive behavior. We tracked the anger and
      aggressive behavior of three of the individuals he taught and the fidelity of his
      teaching of the procedure. According to self and staff reports, anger and
      aggressive behavior of the three individuals decreased to very low levels within
      five months of initiating training and remained at very low levels for the two
      years during which informal data were collected. The fidelity of his teaching the
      procedure was high, if one allows for his idiosyncratic teaching methods. These
      findings suggest that individuals with mild ID, who have mastered an effective
      mindfulness-based strategy to control their aggressive behavior, may be able to
      teach their peers the same strategy to successfully control their anger and
      aggressive behavior to a level that is acceptable for community living.

PMID- 21741207
TI  - Simulation Platform: a cloud-based online simulation environment.
AB  - For multi-scale and multi-modal neural modeling, it is needed to handle multiple
      neural models described at different levels seamlessly. Database technology will
      become more important for these studies, specifically for downloading and
      handling the neural models seamlessly and effortlessly. To date, conventional
      neuroinformatics databases have solely been designed to archive model files, but
      the databases should provide a chance for users to validate the models before
      downloading them. In this paper, we report our on-going project to develop a
      cloud-based web service for online simulation called "Simulation Platform".
      Simulation Platform is a cloud of virtual machines running GNU/Linux. On a
      virtual machine, various software including developer tools such as compilers and
      libraries, popular neural simulators such as GENESIS, NEURON and NEST, and
      scientific software such as Gnuplot, R and Octave, are pre-installed. When a user
      posts a request, a virtual machine is assigned to the user, and the simulation
      starts on that machine. The user remotely accesses to the machine through a web
      browser and carries out the simulation, without the need to install any software
      but a web browser on the user's own computer. Therefore, Simulation Platform is
      expected to eliminate impediments to handle multiple neural models that require
      multiple software.

PMID- 21741208
TI  - A model-based theory on the signal transformation for microsaccade generation.
AB  - The eyes are continuously fluctuating even during fixation. The fluctuations are
      called miniature eye movements and consist of microsaccades, drifts, and tremors.
      It has been revealed that these miniature eye movements aid our vision; they
      improve the visibility of high spatial frequency components, and prevent retinal
      adaptation during fixation. Although the functional roles of the miniature eye
      movements have gradually been uncovered, their generation mechanism remains a
      mystery. Here, we focused on microsaccades, and constructed a neuronal network
      model to explore their generation mechanism. Several lines of evidence ensure
      that microsaccades and saccades share the same neuronal circuitry because they
      fall on the same main sequence, a relationship between their amplitudes and peak
      velocities. In the saccade pathway, saccade commands generated in the superior
      colliculus are relayed to motoneurons via burst neurons (BNs) and the integrator
      network. The BNs are inhibited by omnipause neurons (OPNs) except when saccades
      are generated. We configured a model for microsaccades based on the well-defined
      saccade neuronal pathway including tonic neurons, BNs, OPNs, the integrator
      network, and the eye plant. The model successfully reproduced various
      characteristics of microsaccade: square-wave jerk, single-sided microsaccades,
      and the main sequence. Moreover, during microsaccades, BNs showed low-rate spikes
      due to a partial release from the OPN inhibition. These results suggest that
      microsaccades are generated when BNs are partially, but not completely, released
      from tonic inhibition by OPNs during fixation, in contrast to the generation of
      ordinary saccades in which OPNs pause firing and release BNs from their strong
      inhibition.

PMID- 21741209
TI  - Ultrasound intima-media segmentation using Hough transform and dual snake model.
AB  - Common carotid artery intima-media thickness (IMT), which is usually measured
      upon ultrasound images, is an important indicator to cardiovascular diseases.
      This paper proposes a snake model based segmentation method to automatically
      detect the boundary of intima-media for IMT measurement. In the proposed method,
      two contours are initialized from line segments generated by Hough transform and
      then evolved simultaneously by dual snake model for boundary detection.
      Experimental results show that the proposed method has strong robustness against
      ultrasound artifacts, gives better results than traditional snake model and
      dynamic programming based methods, and achieves similar clinical parameters to
      ground truth data.

PMID- 21741210
TI  - Triangulation as a method to create a preliminary model to identify and intervene
      in intimate partner violence.
AB  - This article examines the possibilities offered by the triangulative approach and
      the challenges using it related to intimate partner violence (IPV) research. The
      purpose of this descriptive, cross-sectional, multicenter study was to create a
      preliminary model for identifying women exposed to acute physical IPV seeking
      care at emergency departments (EDs) and for intervening in the violence. The
      model is based on the results of previous research and the example study. A
      multiple approach was chosen to describe and understand better the factors that
      have an influence on the identification of IPV and its intervention from the
      women's (n = 35) and the ED professional's (n = 480) perspectives. Research
      material was collected from 28 EDs with questionnaires. Secondly, semistructured
      interviews were carried out with 7 women and 20 ED professionals. The data were
      analyzed using quantitative and qualitative methods. The advantage of the
      triangulative approach is that it provides a view of the phenomenon in a variety
      of ways, completing and confirming the results. The problem of this method is
      that it is laborious for the researcher.

PMID- 21741211
TI  - Part I: heart failure home management: patients, multidisciplinary health care
      professionals and family caregivers' perspectives.
AB  - Using qualitative research study methods, this study identified the key factors
      that patients, health care professionals, and family caregivers perceived as most
      helpful in effectively managing heart failure (HF) at home. These key factors
      were the following: (a) family caregiver involvement, (b) continuous learning
      about HF, (c) acceptance of and coping with HF diagnosis, (d) learning from other
      patients with HF, (e) guidance for daily problem solving, (f) lifestyle changes,
      and (g) financial resources.

PMID- 21741212
TI  - Differences in collagen fibres in the capsule walls of parakeratinized and
      orthokeratinized odontogenic cysts.
AB  - Epithelial-mesenchymal interactions are thought to play an important role in the
      pathogenesis of odontogenic lesions. Keratocystic odontogenic tumour (KCOT) is a
      benign cystic neoplasm with a characteristic parakeratinized epithelial lining,
      which differs histologically and behaviourally from the so-called
      orthokeratinized odontogenic cyst (OOC). The purpose of this study was to
      investigate the differences in collagen fibres within the fibrous tissue walls of
      KCOT and OOC. Formalin-fixed paraffin-embedded tissue samples from 15 cases of
      KCOT and 15 cases of OOC were collected. Paraffin sections were stained with
      picrosirius red and observed under a standard light microscope using optical
      polarization. Unicystic ameloblastoma (UA, 15 cases) and subcutaneous epidermoid
      cysts (EC, 15 cases) were included in the study for comparative purposes.
      Significant difference was detected between the polarization colours in the
      fibrous tissue walls of KCOT and OOC (P<0.05), whilst no significant differences
      were found between KCOT and UA and between OOC and EC (P>0.05). The stromal
      collagen fibres of KCOT were different from those of OOC, but similar to those of
      UA, which suggests that the stroma of KOCT may play an important role in
      determining the neoplastic behaviour of the lesion through epithelial-mesenchymal
      interaction.

PMID- 21741213
TI  - Impact of the erythropoietin-derived peptide mimetic Epotris on the
      histopathological consequences of status epilepticus.
AB  - The design of peptide mimetics offers interesting opportunities to selectively
      include beneficial and exclude undesirable effects of a parent molecule. Epotris
      represents a novel erythropoietin mimetic, which lacks an erythropoietic
      activity. The present study evaluates the potential of this peptide to interfere
      with the histopathological consequences of electrical-induced status epilepticus
      in rats. The peptide attenuated status epilepticus-associated expansion of the
      neuronal progenitor cell population in a significant manner. Moreover, Epotris
      affected the number of persistent basal dendrites exhibited by neuronal
      progenitor cells. In contrast, hippocampal cell loss remained unaffected by
      administration of this peptide mimetic. Status epilepticus resulted in obvious
      microglial activation in different brain regions involved in seizure generation
      and spread. Epotris diminished the microglial response caused by prolonged
      seizure activity in the thalamus but not in other brain regions. The study
      renders support that the Epotris' sequences from binding site 2 in helix C of Epo
      play a role in receptor interaction and cytokine function. In addition, the data
      demonstrate that Epotris can exert limited in vivo effects on the cellular
      consequences of prolonged seizure activity. When considering further testing it
      should be taken in mind that Epotris administration only attenuated selected
      cellular consequences of status epilepticus and did not completely prevent
      cellular alterations.

PMID- 21741214
TI  - An epidemiological study of children with status epilepticus in Okayama, Japan:
      incidence, etiologies, and outcomes.
AB  - To clarify the incidence of first-ever episodes of status epilepticus (SE), their
      etiologies and outcomes among Japanese children, we performed an epidemiological
      study in Okayama City. One hundred and twenty patients (69 males, 51 females)
      experienced first-ever SE episodes between 2003 and 2005. Overall, the annual
      incidence of SE was 42.0 per 100,000 population (95% CI: 34.5-49.5). The highest
      incidence was seen in patients aged <2years, especially in the second year of
      life. Febrile SE accounted for 59 (49.2%) cases, and acute-symptomatic etiologies
      accounted for 21. Ten were considered to have remote-symptomatic etiologies, and
      eight to have acute-on-remote-symptomatic etiologies. Ten were classified as
      cryptogenic/idiopathic epilepsy-related, and 12 were unclassified. Nineteen
      (15.8%) patients were diagnosed with exanthema subitum, including three with
      encephalitis/encephalopathy, and 17 (14.2%) patients with influenza, including
      four with encephalitis/encephalopathy. After SE, eight (6.7%) patients suffered
      from motor disturbance with or without mental disturbance. One of these died
      during the follow-up period. Ultimately 34 (28.3%) of the 120 patients had been
      diagnosed with epilepsy by the end of the follow-up. We conclude that the
      incidence of SE among Japanese children is higher than the reported incidence
      among Caucasian children. Febrile SE accounted for approximately half of the
      cases. Among the etiologies, exanthema subitum was the most important infectious
      disease, followed by influenza. Both types of infection caused
      encephalitis/encephalopathy associated with SE as well as febrile SE.

PMID- 21741215
TI  - Attentional guidance during visual search among patients with schizophrenia.
AB  - The current study investigated visual guidance and saccadic selectivity during
      visual search among patients with schizophrenia (SCZ). Data from a previous study
      (Elahipanah, A., Christensen, B.K., & Reingold, E.M., 2008. Visual selective
      attention among persons with schizophrenia: The distractor ratio effect.
      Schizophr. Res. 105, 61-67.) suggested that visual guidance for the less frequent
      distractors in a conjunction search display (i.e., the distractor ratio effect)
      is intact among SCZ patients. The current study investigated the distractor ratio
      effect among SCZ patients when: 1) search is more demanding, and 2) search
      involves motion perception. In addition, eye tracking was employed to directly
      study saccadic selectivity for the different types of distractors. Twenty-eight
      SCZ patients receiving a single antipsychotic medication and 26 healthy control
      participants performed two conjunction search tasks: a within-dimension (i.e.,
      colour * colour) search task; and a cross-dimension (i.e., motion * colour)
      search task. In each task the relative frequency of distractors was manipulated
      across 5 levels. Despite slower search times, patients' eye movement data
      indicated unimpaired visual guidance in both tasks. However, in the motion *
      colour conjunction search task, patients displayed disproportionate difficulty
      detecting the moving target when the majority of distractors were also moving.
      Results demonstrate that bottom-up attentional guidance is unimpaired among
      patients with SCZ; however, patients' impairment in motion discrimination impedes
      their ability to detect a moving target against noisy backgrounds.

PMID- 21741216
TI  - Life expectancy among persons with schizophrenia or bipolar affective disorder.
AB  - CONTEXT: Mortality rates among individuals with schizophrenia or bipolar disorder
      are elevated compared to the general population. OBJECTIVE: The objective was to
      estimate life-expectancy (average age at death) among these persons and make a
      comparison to people in the general population. METHODS: Life-expectancy was
      calculated by means of survival analysis techniques using the entire Danish
      population as a cohort. RESULTS: Life-expectancy was 18.7 years shorter for
      schizophrenic men compared to men in the general population. Corresponding
      numbers for schizophrenic women was 16.3 years, for bipolar men 13.6 years, and
      for bipolar women 12.1 years. CONCLUSIONS: Life-expectancy was much shorter in
      persons with schizophrenia or bipolar disorder. Excess mortality from physical
      diseases and medical conditions exerts a far greater influence on the curtailed
      life-expectancy, when compared against the impact of death by external causes.

PMID- 21741217
TI  - Comparison between young siblings and offspring of subjects with schizophrenia:
      clinical and neuropsychological characteristics.
AB  - INTRODUCTION: High rates of psychopathology and worse performance in cognitive
      areas have been described in high risk (HR) first degree relatives of subjects
      with schizophrenia. The present study aimed to examine clinical and
      neuropsychological characteristics in two different groups of first degree
      relatives of patients with schizophrenia - one of siblings (HRs), and one of
      offspring (HRo) - and compare them with healthy controls (HC). METHODS:
      Participants were 30 HRo, 26 HRs and 33 HC, all aged between 7 and 16 years.
      Clinical and neuropsychological assessments were completed by all participants.
      RESULTS: No significant differences were observed between HR groups in DSM-IV
      diagnoses. The most prevalent diagnosis in both HR samples was attention
      deficit/hyperactivity disorder (ADHD) followed by oppositional defiant disorder
      and generalized anxiety disorder. Both HR groups obtained worse scores than HC on
      prodromal symptoms, premorbid adjustment and behavioral problem scales. In
      cognitive areas, HRo performed worse than HC on most WISC-IV index scores,
      logical memory, visual memory and perceptual organization, whereas HRs only
      performed worse in WISC-IV indexes, logical memory and perceptual organization.
      Most of these differences remained stable after controlling for ADHD. The
      comparison between HRo and HRs showed significant differences in prodromal
      symptoms and working memory after controlling for ADHD. CONCLUSION: Similar
      abnormalities in HRo and HRs were found in relation to clinical and
      neuropsychological variables. Subtle differences were found between HR groups
      with HRo showing difficulties in more clinical and neuropsychological areas than
      HRs and HC. This suggests that, the specific kind of family relationship should
      to be taken into account in future HR research.

PMID- 21741218
TI  - Parametric increases of working memory load unveil a decreased alpha oscillatory
      activity in schizophrenia.

PMID- 21741219
TI  - Outcome in early-onset schizophrenia revisited: findings from the Early Psychosis
      Prevention and Intervention Centre long-term follow-up study.
AB  - OBJECTIVE: To compare the long-term outcome in individuals with early-onset
      (before age 18) and adult-onset schizophrenia spectrum disorder who were
      initially diagnosed and treated in the same clinical center. METHOD: A
      prospective follow-up study of 723 consecutive first-episode psychosis patients
      (age range 14 to 30 years) on average 7.4 years after initial presentation to an
      early psychosis service, the Early Psychosis Prevention and Intervention Centre
      in Melbourne, Australia. The outcome measures included the Brief Psychiatric
      Rating Scale, the Schedule for the Assessment of Negative Symptoms, the Beck
      Depression Inventory, the Global Assessment of Functioning Scale, the Social and
      Occupational Functioning Assessment Scale, and the Quality of Life Scale.
      RESULTS: Follow-up interviews were conducted on 66.9% (484/723) individuals, of
      whom 75.6% (366/484) received a schizophrenia spectrum disorder diagnosis at
      baseline. Early-onset schizophrenia spectrum disorder was observed in 11.2%
      (41/366). At follow-up, individuals with early-onset reported significantly fewer
      positive symptoms and were characterised by significantly superior functioning on
      measures assessing global functioning, social-occupational functioning, and
      community functioning than individuals with adult-onset. The early-onset group
      also achieved significantly better vocational outcomes and had a more favourable
      course of illness with fewer psychotic episodes over the last two years prior to
      follow-up. Finally, when investigated as a continuous variable, younger age at
      onset significantly correlated with better symptomatic and functional outcomes.
      CONCLUSIONS: These results question the assumption that early-onset schizophrenia
      typically has a poor outcome. Early detection and specialised treatment for the
      first psychotic episode appear to be more effective at improving long-term
      functional outcomes in people with early-onset schizophrenia as in those with
      adult-onset schizophrenia. This possibility and the reasons for it need further
      investigation.

PMID- 21741220
TI  - Efficacy and safety of ustekinumab for the treatment of moderate-to-severe
      psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and
      Korean patients (PEARL).
AB  - BACKGROUND: Ustekinumab has been evaluated in Caucasian patients with psoriasis,
      but no studies have been conducted in Asian patients. OBJECTIVE: To assess the
      efficacy and safety of ustekinumab in Taiwanese and Korean patients with moderate
      to-severe psoriasis. METHODS: In this 36-week, multicenter, double-blind, placebo
      controlled study, 121 patients with moderate-to-severe psoriasis were randomized
      (1:1) to receive subcutaneous injections of ustekinumab 45mg at weeks 0, 4, 16 or
      placebo at weeks 0, 4 and ustekinumab 45mg at weeks 12, 16. Efficacy endpoints at
      week 12 included the proportion of patients achieving at least 75% improvement
      from baseline in Psoriasis Area and Severity Index (PASI 75; primary endpoint),
      proportion of patients with Physician's Global Assessment (PGA) of cleared or
      minimal, and change from baseline in Dermatology Life Quality Index (DLQI).
      RESULTS: At week 12, the proportion of patients achieving PASI 75 was 67.2% and
      5.0% in the ustekinumab 45mg and placebo groups, respectively (p<0.001). PGA of
      cleared or minimal was achieved by 70.5% (ustekinumab) and 8.3% (placebo;
      p<0.001), and median DLQI changes were -11.0 and 0.0, respectively (p<0.001).
      Efficacy was maintained through week 28 in ustekinumab-treated patients. Adverse
      event (AE) profiles at week 12 were similar between the ustekinumab and placebo
      groups: 65.6% and 70.0%, respectively, had at least one reported AE. Through week
      36, no disproportionate increase in AEs was observed, with the exception of
      abnormal hepatic function, which was related to concomitant isoniazid treatment
      for latent tuberculosis. Injection-site reactions were rare and mild. No deaths,
      malignancies, or cardiovascular events were reported. CONCLUSIONS: Treatment with
      subcutaneous ustekinumab 45mg offers a favorable benefit/risk profile for
      Taiwanese and Korean patients with moderate-to-severe psoriasis. The efficacy and
      safety profile is consistent with the global phase III studies of ustekinumab in
      psoriasis.

PMID- 21741221
TI  - Factors associated with outcome and duration of therapy in outpatient parenteral
      antibiotic therapy (OPAT) patients with skin and soft-tissue infections.
AB  - This study was designed to identify factors associated with adverse outcomes and
      increased duration of parenteral therapy in patients with skin and soft-tissue
      infections (SSTIs) managed with outpatient parenteral antibiotic therapy (OPAT).
      A retrospective cohort study interrogating variables recorded prospectively in an
      electronic OPAT patient database was performed. 'OPAT failure' was defined as
      hospitalisation following initiation of OPAT, or adverse event or progression of
      infection necessitating a change in antibiotic therapy. Variables associated with
      failure or increased duration of therapy were identified via univariate and
      multiple logistic regression analyses. In total, 963 first patient episodes of
      OPAT-treated SSTIs were observed; 84% were treated with daily ceftriaxone and 15%
      with teicoplanin (three daily loading doses then three times per week).
      Progression of infection was observed in 2.8% of cases, inpatient management was
      required in 6% and significant adverse events occurred in 7.1%. Overall OPAT
      success was 87.1%. Female sex, diabetes and treatment with teicoplanin were
      independently associated with OPAT failure. A significant reduction in duration
      of OPAT therapy was observed over time. A longer duration of intravenous therapy
      was associated with meticillin-resistant Staphylococcus aureus (MRSA), older age,
      vascular disease, a diagnosis of bursitis, and treatment with teicoplanin. Non
      inpatient referrals, management via a nurse-led patient group direction, and
      treatment with ceftriaxone were associated with reduced duration of OPAT. For
      selected patients with SSTIs, OPAT was generally safe and effective, but specific
      patient groups were identified with more complex management pathways and poorer
      outcomes.

PMID- 21741222
TI  - Clinical pharmacokinetic/pharmacodynamic profile of linezolid in severely ill
      intensive care unit patients.
AB  - Severely ill Intensive Care Unit (ICU) patients have an increased risk of
      developing multiresistant Gram-positive infections, largely due to the
      inappropriate use of antimicrobials. In this study, the
      pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid, an antibiotic
      against Gram-positive infections, was characterised in eight critically ill
      patients admitted to the ICU. Remarkable variation amongst patients in the PK
      parameters of linezolid was observed, including a 5-7-fold difference in peak
      serum concentration (C(max)) (mean+/-standard deviation 15.70+/-6.58 mg/L) and 12
      h area under the serum concentration-time curve (AUC(0-12)) (96.73+/-56.45 mg
      h/L), although the minimum inhibitory concentration (MIC) was similar amongst
      patients. In particular, variation amongst patients was found in the ratio of
      AUC(0-24)/MIC (range 31.66-216.82, mean 96.73) and the percentage of time that
      the serum concentration exceeded the MIC (T>MIC) (range 53.4-100%), two
      parameters used to predict linezolid efficacy. These variations highlight the
      importance of individual monitoring of linezolid PK/PD properties in critically
      ill patients. Furthermore, it was observed that regardless of AUC(0-24)/MIC and
      T>MIC values, the clinical and microbiological responses of patients were
      primarily affected by the individual's pathophysiological condition. In summary,
      these findings point to highly variable PK/PD properties of linezolid in severely
      ill patients, providing the rationale for targeting linezolid dosage to each
      individual patient's specific properties. An optimal dosage regimen based on
      individual PK/PD properties and pathophysiological conditions will help reduce
      the occurrence of resistance in Gram-positive bacteria.

PMID- 21741223
TI  - 77Se solid-state NMR investigations on As(x)Se(1-x) glasses using CPMG
      acquisition under MAS.
AB  - (77)Se (I=1/2) solid-state NMR is a very sensitive probe of the local structure
      of selenide glasses, which themselves are promising for optical applications. In
      this work, we show that although (77)Se has a low natural abundance (7.58%) and a
      wide spectral range, the sensitivity can be dramatically increased using Carr
      Purcell-Meiboom-Gill (CPMG) trains of rotor-synchronized pi pulses during the
      detection of (77)Se magnetization but may be affected by chemical shift
      anisotropy when the Magic Angle Spinning rate is not fast enough and by offset
      effects. The indirect dimension of the T(2)(CPMG)-resolved spectrum shows a
      strong influence of the J-couplings between naturally occurring (77)Se pairs. The
      resulting spectra show that the structural model known as "chains crossing model"
      is not entirely suitable to describe the glassy network of the Se-rich
      compositions.

PMID- 21741224
TI  - Preparation, characterization, surface modification and redox reactions of silver
      nanoparticles in the presence of tryptophan.
AB  - The synthesis and characterization of water-soluble dispersions of Ag
      nanoparticles by the reduction of AgNO(3) using tryptophan under alkaline
      synthesis conditions are reported. The Ag nanoparticle formation was very slow at
      low concentration and rapid at extremes. For surface modification and redox
      reactions, manipulating the interparticles interaction controlled the size of Ag
      nanoparticles aggregates. Our results suggest that the replacement of the BH(4)(
      ) ions adsorbed on the nanoparticle surface by tryptophan destabilizes the
      particles and further caused aggregation. A mechanism is proposed for the
      formation of silver nanoparticles by tryptophan. The experimental results are
      supported by theoretical calculations. The Ag nanoparticles were characterized by
      UV-vis absorption, dynamic light scattering and transmission electron microscopy
      techniques.

PMID- 21741225
TI  - The beliefs and knowledge of patients newly diagnosed with cancer in a UK
      ethnically diverse population.
AB  - AIMS: To compare knowledge about the outcome of cancer treatment and beliefs
      about the causes of cancer among British South Asian (BSA) cancer patients of
      predominantly Gujarati origin with the beliefs held by British White (BW) cancer
      patients. We also wanted to determine if these beliefs impacted upon the
      patients' mental health. MATERIALS AND METHODS: We administered a questionnaire
      about cancer beliefs to 94 BSA and 185 BW newly diagnosed cancer patients at the
      Leicestershire Cancer Centre. Using a Likert seven-item scale, we analysed
      patients' views on confidentiality, outcome and cancer treatment and 15 items
      about beliefs about the causes of cancer. Patients also completed the Hospital
      Anxiety and Depression Scale, Patient Health Questionnaire, Mini-MAC, Distress
      Thermometer and newly developed Cancer Insight and Denial, and Physician/Patient
      Trust questionnaires. RESULTS: Most (232/279; 83.2%) believed cancer was curable.
      However, significantly more BSA (10.6% versus 2.7% BW P=0.001) believed cancer
      was incurable. Although most (86.4%) agreed that smoking can cause cancer, there
      was a widespread lack of knowledge of the importance of diet and obesity as
      contributing causes of cancer. There was, in general, an over-emphasis on
      pollution, stress and injury as important aetiological agents. There was a strong
      belief in supernatural involvement in the development of cancer among a minority
      of BSA patients. Twenty per cent of this sample believed that treatment,
      especially surgery, caused the cancer to spread and this was associated with
      significant depression in BSAs (P=0.019) and anxiety in both BW (P=0.006) and BSA
      (P=0.0134) patients. CONCLUSION: Our results show that there is a continual need
      for education about the causes of cancer both in BW and BSA patients.

PMID- 21741226
TI  - Comparison of fibroin cDNAs from webspinning insects: insight into silk formation
      and function.
AB  - Embiopterans (webspinning insects) are renowned for their prolific use of silk.
      These organisms spin silk to construct elaborate networks of tubes in which they
      live, forage, and reproduce. The silken galleries are essential for protecting
      these soft-bodied insects from predators and other environmental hazards. Despite
      the ecological importance of embiopteran silk, very little is known about its
      constituent proteins. Here, we characterize the silk protein cDNAs from four
      embiopteran species to better understand the function and evolution of these
      adaptive molecules. We show that webspinner fibroins (silk proteins) are highly
      repetitive in sequence and possess several conserved characteristics, despite
      differences in habitat preferences across species. The most striking similarities
      are in the codon usage biases of the fibroin genes, particularly in the
      repetitive regions, as well as sequence conservation of the carboxyl-terminal
      regions of the fibroins. Based on analyses of the silk genes, we propose
      hypotheses regarding codon bias and its effect on the translation and replication
      of these unusual genes. Furthermore, we discuss the significance of specific
      fibroin motifs to the mechanical and structural characteristics of silk fibers.
      Lastly, we report that the conservation of webspinner fibroin carboxyl-terminal
      regions suggests that fiber formation may occur through a mechanism analogous to
      that found in Lepidoptera. From these results, insight is gained into the tempo
      and mode of evolution that has shaped embiopteran fibroins.

PMID- 21741227
TI  - Comparison of neoeriocitrin and naringin on proliferation and osteogenic
      differentiation in MC3T3-E1.
AB  - Naringin is considered the main effective compound of Drynaria Rhizome, which is
      used commonly in the treatment of osteoporosis in traditional Chinese medicine.
      However, we found neoeriocitrin, a new compound isolated from Drynaria Rhizome,
      showed a better activity than naringin on proliferation and osteogenic
      differentiation in MC3T3-E1. Both neoeriocitrin and naringin exhibited the best
      effect on proliferation and osteogenic differentiation at concentration of
      2MUg/ml. Neoeriocitrin more significantly improved proliferation and alkaline
      phosphatase (ALP) activity as well as up-regulated Runx2, COLI and OCN expression
      by 56%, 37% and 14% respectively than naringin. Furthermore, neoeriocitrin could
      rescue the inhibition effect of cell differentiation induced by PD98059 to some
      degree. Therefore, neoeriocitrin may be a new promising candidate drug for
      treatment of osteoporosis.

PMID- 21741228
TI  - Effect of Acacia gum on blood pressure in rats with adenine-induced chronic renal
      failure.
AB  - Chronic renal failure (CRF) occurring naturally in patients or induced by
      subtotal nephrectomy in rats induces several alterations in the cardiovascular
      system (CVS). However, the effect of chemically induced CRF in rats on the CVS is
      less well known. We induced CRF in rats by feeding adenine (0.75%, w/w, four
      weeks) and investigated the effect of the ensuing CRF on the systolic and
      diastolic blood pressure (BP) and heart rate (HR). Further, we investigated the
      effect of giving acacia gum (AG, 10%, w/v) in the drinking water concomitantly
      with adenine on the above parameters. AG has been previously shown to ameliorate
      the severity of CRF in humans and rats. We confirmed here that adenine-induced
      CRF significantly increased the plasma concentrations of urea and creatinine, and
      reduced creatinine clearance. Additionally, it significantly increased both
      systolic and diastolic BP, with no significant effect on HR. Both of these
      actions were significantly mitigated by AG treatment. The antihypertensive
      angiotenisn-converting enzyme inhibitor lisinopril (10mg/kg) was given by gavage
      to rats concomitantly with adenine, significantly reduced the rise in blood
      pressure induced by adenine. In conclusion, adenine-induced CRF in rats
      significantly increased BP, and this was significantly mitigated by
      administration of AG. Possible mechanisms of these changes and the protective
      effect of AG will be investigated.

PMID- 21741229
TI  - Electrochemical immunosensor based on electron transfer mediated by graphene
      oxide initiated silver enhancement.
AB  - A new electrochemical immunosensor for the detection of protein biomarker
      platelet-derived growth factor BB (PDGF-BB) was developed based on graphene oxide
      (GO) initiated silver enhancement. The immunosensor was fabricated based on the
      traditional sandwich protocol using secondary anti-PDGF-BB antibody (Ab(2))
      modified GO as label. Gold electrode was first modified with self-assembled
      monolayer (SAM) to block the electron transfer between the electrode and
      K(3)Fe(CN)(6) solution. After the immobilization of primary anti-PDGF-BB antibody
      (Ab(1)) onto electrode via aminidation to the carboxylic group of SAM and the
      formation of the sandwich immuno-structure onto electrode surface, the electrode
      was immersed into silver enhancement solution for silver deposition. The
      deposited metal silver onto GO then mediated electron transfer across the SAM,
      producing redox current. The resulting immunosensor displays a wide range of
      linear response, low detection limit, good reproducibility and stability. The
      immunosensor was used to the detection of PDGF-BB contents in serum samples with
      satisfactory results.

PMID- 21741230
TI  - Lactobacillus brevis CD2 lozenges reduce radiation- and chemotherapy-induced
      mucositis in patients with head and neck cancer: a randomized double-blind
      placebo-controlled study.
AB  - BACKGROUND: Oral mucositis is a frequent and serious complication in patients
      receiving chemo-radiotherapy for head and neck squamous cell carcinoma. This
      study evaluated the effects of administering Lactobacillus brevis CD2 lozenges on
      the incidence and severity of mucositis and tolerance to chemo-radiotherapy.
      METHODS: Two hundred patients suitable for chemo-radiotherapy were enrolled in a
      randomised, double-blind study to receive daily treatment with lozenges
      containing either L. brevis CD2 or placebo. Anticancer therapy was RT 70 Grays/35
      fractions over 7 weeks with weekly Inj. Cisplatin 40 mg/m(2). The study treatment
      was given during, and for 1 week after completion of anticancer therapy. Primary
      end-points were the incidence of grade III and IV oral mucositis and the
      percentage of patients able to complete anticancer treatment. FINDINGS: The
      efficacy analysis included the 188 patients who received >= 1 week of study
      treatment. Grade III and IV mucositis developed in 52% of patients in the L.
      brevis CD2 arm and 77% in the placebo arm (P<0.001). Anticancer treatment
      completion rates were 92% in the L. brevis CD2 arm and 70% in the placebo arm
      (P=0.001). A larger proportion of patients remained free of mucositis when
      treated with L. brevis CD2 (28%) compared to the placebo (7%). INTERPRETATION: L.
      brevis CD2 lozenges reduced the incidence of grade III and IV anticancer therapy
      induced oral mucositis and were associated with a lower overall rate of mucositis
      and a higher rate of anticancer treatment completion.

PMID- 21741231
TI  - New insights of mitochondria reactive oxygen species generation and cell
      apoptosis induced by low dose photodynamic therapy.
AB  - Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts
      cytotoxic activity towards tumour cells by irradiating photosensitisers with
      light exposure to produce reactive oxygen species (ROS). In the current study, we
      have observed that there is an additional production of intracellular ROS during
      low dose PDT. A mitochondrial respiration-deficient cell line (rho(0) cells) was
      investigated to determine the involvement of electron transfer chain (ETC). The
      production of ROS was significantly different between ASTC-a-1 and rho(0)ASTC-a-1
      cells after an identical PDT treatment. Yet, with an increasing Photofrin dose,
      the difference gradually diminished. Pretreatment of the ASTC-a-1 cells with the
      ETC inhibitor rotenone lead the corresponding ROS production to a similar level
      from rho(0)ASTC-a-1 cells subjected to identical PDT protocols. Moreover, we
      found that the difference in intracellular ROS productions between ASTC-a-1 and
      rho(0)ASTC-a-1 cells started during a PDT treatment, while the irradiation was
      still being delivered. A cytotoxicity assay showed that, the ASTC-a-1 cells were
      more sensitive to PDT than rho(0)ASTC-a-1 cells. ROS scavenger n-acetyl-l
      cysteine (NAC) attenuated the toxicity of PDT in both cell lines. Altogether,
      these results indicate that low dose PDT can induce an endogenous ROS production
      via the ETC. This additional endogenous ROS, on top of that from PDT
      photochemical reactions, contributes to an increased cell apoptosis. Thus,
      mitochondria are not only targets but also can be a source of ROS during low dose
      PDT. These results may provide a novel approach to improve PDT applications by
      maximising the efficiency of currently available photosensitisers.

PMID- 21741232
TI  - Production of aromatic green gasoline additives via catalytic pyrolysis of
      acidulated peanut oil soap stock.
AB  - Catalytic pyrolysis was used to generate gasoline-compatible fuel from peanut oil
      soap stock (PSS), a high free fatty acid feedstock, using a fixed-bed reactor at
      temperatures between 450 and 550 degrees C with a zeolite catalyst (HZSM-5). PSS
      fed at 81 gh(-1) along with 100 mL min(-1) inert gas was passed across a 15 g
      catalyst bed (WHSV=5.4h(-1), gas phase residence time=34s). Results indicate that
      fuel properties of PSS including viscosity, heating value, and O:C ratio were
      improved significantly. For PSS processed at 500 degrees C, viscosity was reduced
      from 59.6 to 0.9 mm(2)s(-1), heating value was increased from 35.8 to 39.3 MJL(
      1), and the O:C ratio was reduced from 0.07 to 0.02. Aromatic gasoline components
      (e.g., BTEX), were formed in concentrations as high as 94% (v/v) in catalytically
      cracked PSS with yields ranging from 22% to 35% (v/v of PSS feed).

PMID- 21741233
TI  - Comparative study on enzymatic digestibility of switchgrass varieties and
      harvests processed by leading pretreatment technologies.
AB  - Feedstock quality of switchgrass for biofuel production depends on many factors
      such as morphological types, geographic origins, maturity, environmental and
      cultivation parameters, and storage. We report variability in compositions and
      enzymatic digestion efficiencies for three cultivars of switchgrass (Alamo,
      Dacotah and Shawnee), grown and harvested at different locations and seasons.
      Saccharification yields of switchgrass processed by different pretreatment
      technologies (AFEX, dilute sulfuric acid, liquid hot water, lime, and soaking in
      aqueous ammonia) are compared in regards to switchgrass genotypes and harvest
      seasons. Despite its higher cellulose content per dry mass, Dacotah switchgrass
      harvested after wintering consistently gave a lower saccharification yield than
      the other two varieties harvested in the fall. The recalcitrance of upland
      cultivars and over-wintered switchgrass may require more severe pretreatment
      conditions. We discuss the key features of different pretreatment technologies
      and differences in switchgrass cultivars and harvest seasons on hydrolysis
      performance for the applied pretreatment methods.

PMID- 21741234
TI  - Chemical properties of biocrude oil from the hydrothermal liquefaction of
      Spirulina algae, swine manure, and digested anaerobic sludge.
AB  - This study explores the influence of wastewater feedstock composition on
      hydrothermal liquefaction (HTL) biocrude oil properties and physico-chemical
      characteristics. Spirulina algae, swine manure, and digested sludge were
      converted under HTL conditions (300 degrees C, 10-12 MPa, and 30 min reaction
      time). Biocrude yields ranged from 9.4% (digested sludge) to 32.6% (Spirulina).
      Although similar higher heating values (32.0-34.7 MJ/kg) were estimated for all
      product oils, more detailed characterization revealed significant differences in
      biocrude chemistry. Feedstock composition influenced the individual compounds
      identified as well as the biocrude functional group chemistry. Molecular weights
      tracked with obdurate carbohydrate content and followed the order of
      Spirulina<swine manure<digested sludge. A similar trend was observed in boiling
      point distributions and the long branched aliphatic contents. These findings show
      the importance of HTL feedstock composition and highlight the need for better
      understanding of biocrude chemistries when considering bio-oil uses and upgrading
      requirements.

PMID- 21741235
TI  - Supercritical water gasification of an aqueous by-product from biomass
      hydrothermal liquefaction with novel Ru modified Ni catalysts.
AB  - Supercritical water gasification (SCWG) of glucose solution (50-200 g/L), a
      simulated aqueous organic waste (composed of glucose, acetic acid and guaiacol)
      and a real aqueous organic waste stream generated from a sludge hydrothermal
      liquefaction process was performed in a bench-scale continuous down-flow tubular
      reactor with novel 0.1 RuNi/gamma-Al(2)O(3) or 0.1 RuNi/activated carbon (AC)
      catalyst (10 wt.% Ni with a Ru-to-Ni molar ratio of 0.1). 0.1 RuNi/gamma
      Al(2)O(3) was very effective in catalyzing SCWG of glucose solution and the
      simulated aqueous organic waste, attaining an H(2) yield of 53.9 mol/kg dried
      feedstock at 750 degrees C, 24 MPa and a WHSV of 6h(-1). However, the gamma
      Al(2)O(3)-supported catalyst was not resistant to the attack of alkali and
      nitrogen compounds in the real waste during the SCWG of the real aqueous organic
      waste, whereas the AC-based catalyst exhibited higher stability. This research
      provides a promising approach to the treatment and valorization of aqueous
      organic waste via SCWG.

PMID- 21741236
TI  - Discovery and SAR of 2-arylbenzotriazoles and 2-arylindazoles as potential
      treatments for Duchenne muscular dystrophy.
AB  - Families of 2-arylbenzotriazoles and 2-arylindazoles that show positive effects
      in screens predictive of endogenous utrophin upregulation have been identified.
      Synthesis and structure-activity relationships are described leading to compounds
      with attractive in vitro profiles.

PMID- 21741237
TI  - Synthesis of 6-[18F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa
      with PET.
AB  - 6-Fluoro-PBR28 (N-(6-fluoro-4-phenoxypyridin-3-yl)-N-(2-methoxybenzyl)acetamide),
      a fluorinated analogue of the recently developed TSPO 18 kDa ligand PBR28, was
      synthesized and labelled with fluorine-18. 6-Fluoro-PBR28 and its 6-chloro/6
      bromo counterparts were synthesized in six chemical steps and obtained in 16%,
      10% and 19% overall yields, respectively. Labelling with fluorine-18 was
      performed in one single step (chlorine/bromine-for-fluorine heteroaromatic
      substitution) using a Zymate-XP robotic system affording HPLC-purified, ready-to
      inject, 6-[(18)F]fluoro-PBR28 (>95% radiochemically pure). Non-decay-corrected
      overall yields were 9-10% and specific radioactivities ranged from 74 to 148
      GBq/MUmol. In vitro binding experiments, dynamic MUPET studies performed in a rat
      model of acute neuroinflammation (unilaterally, AMPA-induced, striatum-lesioned
      rats) and ex vivo autoradiography on the same model demonstrated the potential of
      6-[(18)F]fluoro-PBR28 to image the TSPO 18 kDa using PET.

PMID- 21741238
TI  - Evaluation of FKBP and DHFR based destabilizing domains in Saccharomyces
      cerevisiae.
AB  - Two orthogonal destabilizing domains have been developed based on mutants of
      human FKBP12 as well as bacterial DHFR and these engineered domains have been
      used to control protein concentration in a variety of contexts in vitro and in
      vivo. FKBP12 based destabilizing domains cannot be rescued in the yeast
      Saccharomyces cerevisiae; ecDHFR based destabilizing domains are not degraded as
      efficiently in S. cerevisiae as in mammalian cells or Plasmodium, but provide a
      starting point for the development of domains with increased signal-to-noise in
      S. cerevisiae.

PMID- 21741239
TI  - Biphenyl/diphenyl ether renin inhibitors: filling the S1 pocket of renin via the
      S3 pocket.
AB  - Structure-based design led to the discovery of a novel class of renin inhibitors
      in which an unprecedented phenyl ring filling the S1 site is attached to the
      phenyl ring filling the S3 pocket. Optimization for several parameters including
      potency in the presence of human plasma, selectivity against CYP3A4 inhibition
      and improved rat oral bioavailability led to the identification of 8d which
      demonstrated antihypertensive efficacy in a transgenic rat model of human
      hypertension.

PMID- 21741240
TI  - Hereditary peripheral neuropathies of childhood: an overview for clinicians.
AB  - This review focuses on the "pure" hereditary peripheral neuropathies where
      peripheral nerve disease is the main manifestation and does not address
      neurodegenerative disorders associated with but not dominated by peripheral
      neuropathy. Aetiologies of childhood-onset peripheral neuropathies differ from
      those of adult-onset, with more inherited conditions, especially autosomal
      recessive. Charcot-Marie-Tooth disease is the commonest neuromuscular disorder.
      The genetic labels of CMT (Charcot-Marie-Tooth) disease types 1-4 are the
      preferred sub-type terms. Clinical presentations and molecular genetic
      heterogeneity of hereditary peripheral neuropathies are diverse. For most
      patients worldwide, diagnostic studies are limited to clinical assessment. Such
      markers which could be used to identify specific sub-types include presentation
      in early childhood, scoliosis, marked sensory involvement, respiratory
      compromise, upper limb involvement, visual or hearing impairment, pyramidal signs
      and mental retardation. These key markers may assist targeted genetic testing and
      aid in diagnosing children where DNA testing is not possible.

PMID- 21741241
TI  - Novel mutations in the PRX and the MTMR2 genes are responsible for unusual
      Charcot-Marie-Tooth disease phenotypes.
AB  - Autosomal recessive Charcot-Marie-Tooth diseases, relatively common in Algeria
      due to high prevalence of consanguineous marriages, are clinically and
      genetically heterogeneous. We report on two consanguineous families with
      demyelinating autosomal recessive Charcot-Marie-Tooth disease (CMT4) associated
      with novel homozygous mutations in the MTMR2 gene, c.331dupA (p.Arg111LysfsX24)
      and PRX gene, c.1090C>T (p.Arg364X) respectively, and peculiar clinical
      phenotypes. The three patients with MTMR2 mutations (CMT4B1 family) had a typical
      phenotype of severe early onset motor and sensory neuropathy with typical focally
      folded myelin on nerve biopsy. Associated clinical features included vocal cord
      paresis, prominent chest deformities and claw hands. Contrasting with the
      classical presentation of CMT4F (early-onset Dejerine-Sottas phenotype), the four
      patients with PRX mutations (CMT4F family) had essentially a late age of onset
      and a protracted and relatively benign evolution, although they presented marked
      spine deformities. These observations broaden the spectrum of clinical phenotypes
      associated with these two CMT4 forms.

PMID- 21741242
TI  - Gait initiation in older people--Time to first lateral movement may be the
      measure of choice.
AB  - AIMS: There are few empirical data to guide the choice of a gait initiation (GI)
      measure in older people. We investigated the statistical characteristics of the
      components of GI, their inter-relationships and associations with sensorimotor
      variables, and the effect on them of cognitive interference. METHODS: GI was
      measured for randomly selected participants aged 60-86 years using a force
      platform with and without a cognitive interference task. Sensorimotor measures
      were obtained using the physiological profile assessment (PPA), and cognitive
      speed using the digit symbol and symbol search tests. GI was divided into its
      three components: time to first lateral movement (FLM); transfer time; and swing
      time. Six summary indices were assessed for suitability. Regression techniques
      and Spearman correlations were used to examine learning effects, inter
      relationships between components, associations with other study factors and
      responsiveness to cognitive interference. RESULTS: The median of trials per
      participant was the best summary index. Learning effects were observed under
      single and particularly dual-tasking. Time to FLM was most consistently
      associated with age, height, weight, sensorimotor variables, falls-risk score and
      cognitive speed, and was most responsive to dual-tasking. Overall time to GI was
      more predictive of falls risk than was time to FLM. CONCLUSIONS: Multiple trials
      are recommended for GI component measurement and the median may provide the best
      summary measure across trials. Time to FLM is the GI component measure of choice
      in older people due to its relationship with other factors and responsiveness to
      cognitive interference but without advantage over overall time to GI.

PMID- 21741243
TI  - In-shoe plantar pressure measurements for patients with knee osteoarthritis:
      Reliability and effects of lateral heel wedges.
AB  - Although plantar pressure measurement systems are being used increasingly during
      gait analyses to investigate foot orthotics, there is limited information
      describing test-retest reliability of such measurements. Objectives of this study
      were to (1) examine the test-retest reliability of lateral heel pressure (LHP)
      and centre of pressure (COP) during walking with and without lateral heel wedges,
      and (2) evaluate the effects of 4 degrees  and 8 degrees  lateral heel wedges on
      the magnitude of LHP, the pathway of the COP and the peak external knee adduction
      moment (KAM) in subjects with and without knee osteoarthritis (OA). Twenty-six
      subjects, 12 patients with knee OA and 14 healthy subjects, were evaluated during
      three lateral heel wedge conditions (control, 4 degrees  and 8 degrees ) with
      standardized footwear. Three-dimensional analyses of gait with optical motion
      capture, floor-mounted force plate and in-shoe plantar pressure were completed on
      two occasions. Intraclass correlation coefficients (ICC(2, 1)) for LHP were
      excellent (0.79-0.83) while ICCs for COP in the medial-lateral and anterior
      posterior directions were more variable (0.66-0.86). Reliability was slightly
      diminished when using heel wedges. Standard errors of measurement suggested
      considerable day-to-day variability in an individual's measures. Lateral heel
      wedges significantly (p<0.001) increased LHP, shifted COP anteriorly and
      laterally, and decreased the KAM. No significant differences were observed
      between subjects with and without OA. Although the day-to-day variability appears
      too large to confidently evaluate changes in individual patients, and decreases
      in reliability with increases in wedge size indicate caution, these results
      suggest in-shoe measurement of LHP and COP are appropriate for use in studies
      evaluating biomechanical effects of foot orthoses for knee OA.

PMID- 21741244
TI  - Copy number imbalances in blood and hair in monozygotic twins discordant for
      amyotrophic lateral sclerosis.
AB  - Chromosomal copy number association studies in patients with amyotrophic lateral
      sclerosis (ALS) using blood DNA have so far been inconclusive. We employed genome
      wide screening to look for copy number imbalances (CNIs) between blood and hair
      DNA from three ALS-discordant monozygotic twin pairs and two phenotypically
      normal monozygotic twin pairs. Genome-wide chromosomal copy number was estimated
      using AffyMetrix 6.0 GeneChips. CNIs were sought both between twin pairs and
      between blood and hair DNA from the same individuals. Two blood CNIs were found
      in one ALS-discordant twin pair. In another ALS-discordant twin pair, seven hair
      CNIs were detected. CNIs were also found between blood and hair in three
      individuals. Imbalances in blood copy number appear to be rare in monozygotic
      twin pairs, but hair may harbour more CNIs than blood. Copy number differences
      between blood and hair from the same individuals appear to be common. Since brain
      and hair share a common ectodermal origin, hair may be a more suitable tissue
      than blood to estimate somatic copy number variation in the brain.

PMID- 21741245
TI  - Awake far lateral craniotomy for resection of foramen magnum meningioma in a
      patient with tenuous motor and somatosensory evoked potentials.
AB  - We report a patient with an infratentorial lesion resected under a far-lateral
      approach during awake craniotomy to optimize intraoperative monitoring. A 72-year
      old man presented with falls, difficulty walking, and lower extremity weakness.
      MRI revealed a 2.2 by 2.3 by 2.8 cm mass at the right cervicomedullary junction,
      with mass effect on the adjacent spinal cord. During two attempts during surgical
      positioning under general anesthesia, motor evoked potentials were lost. Each
      time the operation was aborted. During the third operation, the patient underwent
      monitored, light anaesthesia and was awakened periodically to confirm conscious
      motor function. The operation proceeded without complication, and postoperatively
      there was no further decrease in motor function. This is, to our knowledge, the
      first use of an awake operation for an infratentorial meningioma via the far
      lateral approach, demonstrating the technique may be used safely and can be
      useful in optimizing motor function monitoring.

PMID- 21741246
TI  - Cdc48: a power machine in protein degradation.
AB  - Cdc48 is an essential, highly prominent ATP driven machine in eukaryotic cells.
      Physiological function of Cdc48 has been found in a multitude of cellular
      processes, for instance cell cycle progression, homotypic membrane fusion,
      chromatin remodeling, transcriptional and metabolic regulation, and many others.
      The molecular function of Cdc48 is arguably best understood in endoplasmic
      reticulum-associated protein degradation by the ubiquitin proteasome system. In
      this review, we summarize the general characteristics of Cdc48/p97 and the most
      recent results on the molecular function of Cdc48 in some of the above processes,
      which were found to finally end in proteolysis-connected pathways, either
      involving the proteasome or autophagocytosis-mediated lysosomal degradation.

PMID- 21741247
TI  - Development of 3-substituted-androsterone derivatives as potent inhibitors of
      17beta-hydroxysteroid dehydrogenase type 3.
AB  - 17Beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3) is a steroidogenic
      enzyme that catalyzes the transformation of 4-androstene-3,17-dione (Delta4
      dione) into androgen testosterone (T). To provide effective inhibitors of
      androgen biosynthesis, we synthesized two different series (amines and
      carbamates) of 3beta-substituted-androsterone derivatives and we tested their
      inhibitory activity on 17beta-HSD3. From the results of our structure-activity
      relationship study, we identified a series of compounds producing a strong
      inhibition of 17beta-HSD3 overexpressed in HEK-293 cells (homogenized cells). The
      most active compound when tested in intact HEK-293 transfected cells, namely
      (3alpha,5alpha)-3-{[trans-2,5-dimethyl-4-{[2-(trifluoromethyl)phenyl]
      sulfonyl}piperazin-1-yl]methyl}-3-hydroxyandrostan-17-one (15b), shows an IC50
      value of 6 nM, this compound is thus eight times more active than our reference
      compound D-5-2 (IC50=51 nM). This new improved inhibitor did not stimulate the
      proliferation of androgen-sensitive Shionogi cells, suggesting a non-androgenic
      profile. Compound 15b is thus a good candidate for further in vivo studies on
      rodents.

PMID- 21741248
TI  - Molecular factors governing inhibition of arylimidamides against Leishmania:
      conservative computational modeling to improve chemotherapies.
AB  - A dataset of 55 compounds with inhibitory activity against Leishmania donovani
      axenic amastigotes and Leishmania amazonensis intracellular parasites was
      examined through three-dimensional quantitative structure-activity relationship
      modeling employing molecular descriptors from both rigid and flexible compound
      alignments. For training and testing purposes, the compounds were divided into
      two datasets of 45 and 10 compounds, respectively. Statistically significant
      models were constructed and validated via the internal and external predictions.
      For all models employing steric, electrostatic, hydrophobic, H-donor and H
      acceptor molecular descriptors, the R2 values were greater than 0.90 and the SEE
      values were less than 0.22. The models obtained from rigid and flexible compounds
      were employed together to obtain a conservative method for predictions. This
      method minimized under predictions. Molecular descriptors from the models were
      then extrapolated, for the overall predictive devices and the individual
      compounds, and examined with regard to inhibitory activity. Information gained
      from the molecular descriptors is useful in the design of novel compounds. The
      models obtained can be employed to predict activities of the compounds designed
      and/or form predictions for compounds that exist and have not yet been examined
      with biological inhibitory assays.

PMID- 21741249
TI  - Arthrinins A-D: novel diterpenoids and further constituents from the sponge
      derived fungus Arthrinium sp.
AB  - Bioassay-guided fractionation of a methanolic extract of the fungus Arthrinium
      sp., isolated from the Mediterranean sponge Geodia cydonium, afforded 10 natural
      products including five new diterpenoids, arthrinins A-D (1-4) and myrocin D (5).
      In addition, five known compounds were obtained, which included myrocin A (6),
      norlichexanthone (7), anomalin A (8), decarboxycitrinone (9) and 2,5-dimethyl-7
      hydroxychromone (10). The structures of all isolated compounds were unambiguously
      elucidated based on extensive 1D and 2D NMR and HR-MS analyzes. The absolute
      configuration of arthrinins A-D (1-4) was established by the convenient Mosher
      method performed in NMR tubes and by interpretation of the ROESY spectra.
      Antiproliferative activity of the isolated compounds was assessed in vitro
      against four different tumor cell lines, including mouse lymphoma (L5178Y), human
      chronic myelogenous leukemia (K562), human ovarian cancer (A2780) and cisplatin
      resistant ovarian cancer cells (A2780CisR), using the MTT assay. Norlichexanthone
      (7) and anomalin A (8) exhibited the strongest activities with IC50 values
      ranging from 0.40 to 74.0 MUM depending on the cell line investigated. This was
      paralleled by the inhibitory activity of both compounds against 16 cancer related
      protein kinases including aurora-B, PIM1, and VEGF-R2. In vitro IC50 values of 7
      and 8 against these three protein kinases ranged from 0.3 to 11.7 MUM. Further
      investigation of the potential antitumoral activity of compounds 5-8 was
      performed in an in vitro angiogenesis assay against human umbilical vascular
      endothelial cells (HUVEC) sprouting induced by vascular endothelial growth factor
      A (VEGF-A). Anomalin A (8), myrocin D (5) and myrocin A (6) inhibited VEGF-A
      dependent endothelial cell sprouting with IC50 values of 1.8, 2.6 and 3.7 MUM,
      respectively, whereas norlichexanthone (7) was inactive.

PMID- 21741250
TI  - Synthesis, molecular modeling and biological evaluation of beta-ketoacyl-acyl
      carrier protein synthase III (FabH) as novel antibacterial agents.
AB  - A series of novel cinnamic acid secnidazole ester derivatives have been designed
      and synthesized, and their biological activities were also evaluated as potential
      inhibitors of FabH. These compounds were assayed for antibacterial activity
      against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and
      Staphylococcus aureus. Compounds with potent antibacterial activities were tested
      for their E. coli FabH inhibitory activity. Compound 3n showed the most potent
      antibacterial activity with MIC of 1.56-6.25 MUg/mL against the tested bacterial
      strains and exhibited the most potent E. coli FabH inhibitory activity with IC50
      of 2.5 MUM. Docking simulation was performed to position compound 3n into the E.
      coli FabH active site to determine the probable binding conformation.

PMID- 21741251
TI  - Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine
      analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid.
AB  - INTRODUCTION: The enantiomerically enriched (ee=90%, enantiomer 1) synthetic
      amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2
      [(18)F]FACPC-1) accumulates in malignant cells by elevated transport through the
      sodium-independent system-L (leucine preferring) amino acid transporter. The
      purpose of this study was to evaluate in vivo uptake and single-dose toxicity of
      anti-2-[(18)F]FACPC-1 in animals as well as the individual organ and whole-body
      dose in humans. METHODS: A DU145 xenograft rodent model was used to measure anti
      2-[(18)F]FACPC-1 uptake at 15, 30 and 60 min post-injection. Animals were
      sacrificed and organs harvested to measure the percent injected activity per
      organ and to calculate residence time. Anti-2-[(18)F]FACPC-1 toxicity was
      assessed using a single microdose (37-74 MBq/kg) in nonhuman primates. Their
      vital signs were monitored for 2 h post-injection for drug-related effects. Human
      biodistribution studies were collected by sequential whole-body PET/CT scans on
      six healthy volunteers (three male and three female) for 120 min following a
      single 247+/-61 MBq bolus injection of anti-2-[(18)F]FACPC-1. Estimates of
      radiation dose from anti-2-[(18)F]FACPC-1 to the human body were calculated using
      recommendations of the MIRD committee and MIRDOSE 3.0 software. RESULTS: High
      anti-2-[(18)F]FACPC-1 residence time was observed in the pancreas of the rodent
      model compared to the human data. No abnormal treatment-related observations were
      made in the nonhuman primate toxicity studies. Human venous blood showed no
      metabolites of anti-2-[(18)F]FACPC-1 in the first 60 min post-injection. All
      volunteers showed initially high uptake in the kidneys followed by a rapid
      washout phase. The estimated effective dose equivalent was 0.0196 mSv/MBq.
      CONCLUSION: Anti-2-[(18)F]FACPC-1 showed low background uptake in the brain,
      thoracic and abdominal cavities of humans, suggesting a possible use for
      detecting malignant tissues in these regions.

PMID- 21741252
TI  - An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate.
AB  - INTRODUCTION: [(18)F]Mefway is a serotonin 5-HT(1A) PET radiotracer with high
      specificity and favorable in vivo imaging properties. The chemical structure of
      [(18)F]mefway permits (18)F labeling in either the cis or trans positions at the
      4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans
      [(18)F]mefway in the nonhuman primate. In this work, we compare the in vivo
      binding of cis-[(18)F]mefway and trans-[(18)F]mefway to evaluate the properties
      of cis-[(18)F]mefway for 5-HT(1A) PET imaging. METHODS: The cis- and trans
      [(18)F]mefway tracers were synthesized via nucleophilic substitution with their
      respective tosyl precursors. Two monkeys (one male, one female) were given bolus
      injections of both cis- and trans-labeled [(18)F]mefway in separate experiments.
      Dynamic scans were acquired for 90 min with a microPET P4 scanner. Time-activity
      curves were extracted in the areas of the mesial temporal cortex (MTC), anterior
      cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN) and cerebellum
      (CB). The in vivo behavior of the radiotracers was compared based upon the
      nondisplaceable binding potential (BP(ND)) using the CB as a reference region.
      RESULTS: Averaged over the two subjects, BP(ND) values were as follows: MTC: 7.7,
      0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13, for trans-[(18)F]mefway
      and cis-[(18)F]mefway, respectively. CONCLUSION: The cis-labeled [(18)F]mefway
      tracer has low specific binding throughout the 5-HT(1A) regions of the brain
      compared to trans-[(18)F]mefway, suggesting that the target-to-background binding
      of cis-[(18)F]mefway may limit its use for in vivo assessment of 5-HT(1A)
      binding.

PMID- 21741253
TI  - Three-dimensional quantitation of regional cerebral blood flow in mice using a
      high-resolution pinhole SPECT system and 123I-iodoamphetamine.
AB  - INTRODUCTION: This study is intended to evaluate the feasibility of using a high
      resolution pinhole SPECT system and iodine-123-N-isopropyl-4-iodoamphetamine
      ((123)I-IMP) for three-dimensional (3D) absolute quantitation of regional
      cerebral blood flow (rCBF) in mice. METHODS: The pinhole SPECT system consists of
      a rotating stage and a pinhole collimator attached to a clinical gamma camera.
      The collimator's focal length is 251 mm. Phantom studies were performed to
      evaluate sensitivity and full-width half-maximum (FWHM) spatial resolution. The
      aperture-to-object distance was 15 mm. Six mice were studied. Cerebral
      infarctions were induced by ligating and disconnecting the distal portion of the
      left middle cerebral artery. Ex vivo SPECT studies were performed using harvested
      brains and skulls. The CBF volumetric image was computed using the standardized
      input function. RESULTS: Excellent spatial resolution of 0.9-mm FWHM and uniform
      sensitivity throughout the 3D volume were demonstrated in the phantom
      experiments. The CBF images showed a defect in the infarcted areas and a
      reduction of CBF values in the infarcted region as compared with the control
      region. CONCLUSIONS: This study demonstrated the feasibility of the 3D
      quantitation of rCBF in mice using a high-resolution pinhole SPECT system and
      (123)I-IMP.

PMID- 21741254
TI  - [18F]Fluoroazabenzoxazoles as potential amyloid plaque PET tracers: synthesis and
      in vivo evaluation in rhesus monkey.
AB  - INTRODUCTION: An (18)F-labeled positron emission tomography (PET) tracer for
      amyloid plaque is desirable for early diagnosis of Alzheimer's disease,
      particularly to enable preventative treatment once effective therapeutics are
      available. Similarly, such a tracer would be useful as a biomarker for enrollment
      of patients in clinical trials for evaluation of antiamyloid therapeutics.
      Furthermore, changes in the level of plaque burden as quantified by an amyloid
      plaque PET tracer may provide valuable insights into the effectiveness of amyloid
      targeted therapeutics. This work describes our approach to evaluate and select a
      candidate PET tracer for in vivo quantification of human amyloid plaque. METHODS:
      Ligands were evaluated for their in vitro binding to human amyloid plaques,
      lipophilicity and predicted blood-brain barrier permeability. Candidates with
      favorable in vitro properties were radiolabeled with (18)F and evaluated in vivo.
      Baseline PET scans in rhesus monkey were conducted to evaluate the regional
      distribution and kinetics of each tracer using tracer kinetic modeling methods.
      High binding potential in cerebral white matter and cortical grey matter was
      considered an unfavorable feature of the candidate tracers. RESULTS: [(18)F]MK
      3328 showed the most favorable combination of low in vivo binding potential in
      white matter and cortical grey matter in rhesus monkeys, low lipophilicity (Log
      D=2.91) and high affinity for human amyloid plaques (IC(50)=10.5+/-1.3 nM).
      CONCLUSIONS: [(18)F]MK-3328 was identified as a promising PET tracer for in vivo
      quantification of amyloid plaques, and further evaluation in humans is warranted.

PMID- 21741255
TI  - Changes: choosing a target?

PMID- 21741256
TI  - Effects of hypoxic-ischemic brain injury on striatal dopamine transporter in
      newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification.
AB  - INTRODUCTION: Alterations of dopamine in striatal presynaptic terminals play an
      important role in the hypoxic-ischemic (HI) brain injury. Quantification of DAT
      levels in the presynaptic site using (11)C-N-2-carbomethoxy-3-(4-fluorophenyl)
      tropane ((11)C-CFT) with positron emission tomography (PET) was applied in
      studies for Parkinson's disease. The current study investigated the changes in
      striatal DAT following HI brain injury in newborn piglets using (11)C-CFT PET.
      METHODS: Newborn piglets were subjected to occlusion of bilateral common carotid
      arteries for 30 min and simultaneous peripheral hypoxia. Brain DAT imaging was
      performed using PET/CT with (11)C-CFT as the probe in each group (including the
      control group and HI insult groups). Brain tissues were collected for DAT
      immunohistochemical (IHC) analysis at each time point post the PET/CT procedure.
      Sham controls had some operation without HI procedure. RESULTS: A few minutes
      after intravenous injection of (11)C-CFT, radioactive signals for DAT clearly
      appeared in the cortical area, striatum and cerebellum of newborn piglets of sham
      control group and HI insult groups. HI brain insult markedly increased striatal
      DAT at an early period (P<.05 vs. sham controls) when neuronal pathological
      changes were mild. Changes in striatal DAT were absent at later period post-HI
      insult when neuronal injury became more severe. (11)C-CFT PET imaging data and
      IHC DAT staining data were highly correlated (r=0.844, P<.05). CONCLUSIONS: HI
      brain injury resulted in a transient increase in striatal DAT. (11)C-CFT PET/CT
      imaging data reflected the dynamic changes of DAT in the striatum in vivo.

PMID- 21741257
TI  - Improved quality control of [18F]fluoromethylcholine.
AB  - OBJECTIVES: With respect to the broad application of [(18)F-methyl]fluorocholine
      (FCH), there is a need for a safe, but also efficient and convenient way for
      routine quality control of FCH. Therefore, a GC- method should be developed and
      validated which allows the simultaneous quantitation of all chemical impurities
      and residual solvents such as acetonitrile, ethanol, dibromomethane and N,N
      dimethylaminoethanol. METHODS: Analytical GC has been performed with a GC
      capillary column Optima 1701 (50 m*0.32 mm), and a pre-column deactivated
      capillary column phenyl-Sil (10 m*0.32) in line with a flame ionization detector
      (FID) was used. The validation includes the following tests: specificity, range,
      accuracy, linearity, precision, limit of detection (LOD) and limit of
      quantitation (LOQ) of all listed substances. RESULTS: The described GC method has
      been successfully used for the quantitation of the listed chemical impurities.
      The specificity of the GC separation has been proven by demonstrating that the
      appearing peaks are completely separated from each other and that a resolution
      R>=1.5 for the separation of the peaks could be achieved. The specified range
      confirmed that the analytical procedure provides an acceptable degree of
      linearity, accuracy and precision. For each substance, a range from 2% to 120% of
      the specification limit could be demonstrated. The corresponding LOD values were
      determined and were much lower than the specification limits. CONCLUSIONS: An
      efficient and convenient GC method for the quality control of FCH has been
      developed and validated which meets all acceptance criteria in terms of
      linearity, specificity, precision, accuracy, LOD and LOQ.

PMID- 21741258
TI  - Effect of chelator conjugation level and injection dose on tumor and organ uptake
      of 111In-labeled MORAb-009, an anti-mesothelin antibody.
AB  - INTRODUCTION: Radiolabeling of a monoclonal antibody (mAb) with a metallic
      radionuclide requires the conjugation of a bifunctional chelator to the mAb. The
      conjugation, however, can alter the physical and immunological properties of the
      mAb, consequently affecting its tumor-targeting pharmacokinetics. In this study,
      we investigated the effect of the amount of 2-(p-isothiocyanatobenzyl)-cyclohexyl
      diethylenetriamine-pentaacetic acid (CHX-A") conjugated to MORAb-009, a mAb
      directed against mesothelin, and the effect of MORAb dose on the biodistribution
      of (111)In-labeled MORAb-009. METHODS: We used nude mice bearing the A431/K5
      tumor as a mesothelin-positive tumor model and the A431 tumor as a mesothelin
      negative control. To find the optimal level of CHX-A" conjugation, CHX-A"-MORAb
      009 conjugates with 2.4, 3.5 and 5.5 CHX-A" molecules were investigated. To
      investigate the effect of injected MORAb-009 dose on neutralizing the shed
      mesothelin in the circulation, biodistribution studies were performed after the
      intravenous co-injection of (111)In-labeled MORAb-009 (2.4 CHX-A"/MORAb-009) with
      three different doses: 0.2, 2 and 30 MUg of MORAb-009. RESULTS: The tumor uptake
      in A431/K5 tumor was four times higher than that in A431 tumor, indicating that
      the tumor uptake in A431/K5 was mesothelin mediated. The conjugate with 5.5 CHX
      A" showed a lower isoelectric point (pI) and lower immunoreactivity (IR) than the
      2.4 CHX-A" conjugate. These differences were reflected in the biodistribution of
      the (111)In label. The (111)In-labeled MORAb-009 conjugated with 2.4 CHX-A"
      produced higher tumor uptake and lower liver and spleen uptakes than the 5.5 CHX
      A" conjugate. The biodistribution studies also revealed that the tumor uptake was
      significantly affected by the injected MORAb-009 dose and tumor size. The 30-MUg
      dose produced higher tumor uptake than the 0.2- and 2-MUg doses, whereas the 30
      MUg dose produced lower liver and spleen uptakes than the 0.2-MUg dose.
      CONCLUSION: This study demonstrates that the number of chelate conjugation and
      the injected dose are two important parameters to achieve high tumor and low non
      target organ uptake of (111)In-labeled MORAb-009. This study also suggests that
      the injected dose of mAb could be individualized based on the tumor size or the
      blood level of shed antigen in a patient to achieve the ideal tumor-to-organ
      radioactivity ratios.

PMID- 21741259
TI  - Development and validation of the 57Co assay for determining the ligand to
      antibody ratio in bifunctional chelate/antibody conjugates for use in
      radioimmunotherapy.
AB  - INTRODUCTION: The ligand to antibody ratio is an important characteristic of a
      chelate/antibody conjugate. It has been widely reported that if the ratio is too
      high, there will be detrimental effects on immunoreactivity and biodistribution;
      conversely, if the ratio is too low, the radionuclide may not bind efficiently,
      and the stability and the specific activity will be reduced. There are little
      published data on the accuracy or precision of the (57)Co assay. The UK Clinical
      Trials Regulations state that "systems with procedures that assure the quality of
      every aspect of the trial should be implemented". The aims of this study were to
      assess the reliability and accuracy of the (57)Co binding assay and validate it
      against defined criteria. METHOD: Thirty-two serial assays were assessed for
      reliability. Two batches of conjugated antibody were also analysed by matrix
      assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry
      (MS) to allow the comparison of the functional test with a physical method.
      RESULTS: Reliability: The coefficient of variation was 0.13. Accuracy: There was
      9% variation between the (57)Co binding assay and MALDI-TOF MS results.
      CONCLUSION: A detailed method for the (57)Co ligand to antibody test is described
      that allows a discrete value to be obtained. The assay was validated as fit for
      purpose against target values of coefficient of variation <0.20, accuracy+/-10%,
      over a permissive range of 0.5-3.0 ligand to antibody ratio.

PMID- 21741260
TI  - The synthesis, magnetic purification and evaluation of 99mTc-labeled
      microbubbles.
AB  - INTRODUCTION: Ultrasound (US) contrast agents based on microbubbles (MBs) are
      being investigated as platforms for drug and gene delivery. A methodology for
      determining the distribution and fate of modified MBs quantitatively in vivo can
      be achieved by tagging MBs directly with (99m)Tc. This creates the opportunity to
      employ dual-modality imaging using both US and small animal SPECT along with
      quantitative ex vivo tissue counting to evaluate novel MB constructs. METHODS: A
      (99m)Tc-labeled biotin derivative ((99m)TcL1) was prepared and incubated with
      streptavidin-coated MBs. The (99m)Tc-labeled bubbles were isolated using a
      streptavidin-coated magnetic-bead purification strategy that did not disrupt the
      MBs. A small animal scintigraphic/CT imaging study as well as a quantitative
      biodistribution study was completed using (99m)TcL1 and (99m)Tc-labeled bubbles
      in healthy C57Bl-6 mice. RESULTS: The imaging and biodistribution data showed
      rapid accumulation and retention of (99m)Tc-MBs in the liver (68.2+/-6.6 %ID/g at
      4 min; 93.3+/-3.2 %ID/g at 60 min) and spleen (214.2+/-19.7 %ID/g at 4 min;
      213.4+/-19.7 %ID/g at 60 min). In contrast, (99m)TcL1 accumulated in multiple
      organs including the small intestine (22.5+/-3.6 %ID/g at 4 min; 83.4+/-5.9 %ID/g
      at 60 min) and bladder (184.0+/-88.1 %ID/g at 4 min; 24.2+/-17.7 %ID/g at 60
      min). CONCLUSION: A convenient means to radiolabel and purify MBs was developed
      and the distribution of the labeled products determined. The result is a platform
      which can be used to assess the pharmacokinetics and fate of novel MB constructs
      both regionally using US and throughout the entire subject in a quantitative
      manner by employing small animal SPECT and tissue counting.

PMID- 21741261
TI  - Manipulation of hemoglobin expression affects Arabidopsis shoot organogenesis.
AB  - Over the past few years non-symbiotic plant hemoglobins have been described in a
      variety of plant species where they fulfill several functions ranging from
      detoxification processes to basic aspects of plant growth and post-embryonic
      development. To date no information is available on the role of hemoglobins
      during in vitro morphogenesis. Shoot organogenesis was induced in Arabidopsis
      lines constitutively expressing class 1, 2 and 3 hemoglobins (GLB1, 2 and 3) and
      lines in which the respective genes were either downregulated by RNAi (GLB1) or
      knocked out (GLB2 and GLB3). The process was executed by culturing root explants
      on an initial auxin-rich callus induction medium (CIM) followed by a transfer
      onto a cytokinin-containing shoot induction medium (SIM). While the repression of
      GLB2 inhibited organogenesis the over-expression of GLB1 or GLB2 enhanced the
      number of shoots produced in culture, and altered the transcript levels of genes
      participating in cytokinin perception and signalling. The up-regulation of GLB1
      or GLB2 activated CKI1 and AHK3, genes encoding cytokinin receptors and affected
      the transcript levels of cytokinin responsive regulators (ARRs). The expression
      of Type-A ARRs (ARR4, 5, 7, 15, and 16), feed-back repressors of the cytokinin
      pathway, was repressed in both hemoglobin over-expressors whereas that of several
      Type-B ARRs (ARR2, 12, and 13), transcription activators of cytokinin-responsive
      genes, was induced. Such changes enhanced the sensitivity of the root explants to
      cytokinin allowing the 35S::GLB1 and 35S::GLB2 lines to produce shoots at low
      cytokinin concentrations which did not promote organogenesis in the WT line.
      These results show that manipulation of hemoglobin can modify shoot organogenesis
      in Arabidopsis and possibly in those systems partially or completely unresponsive
      to applications of exogenous cytokinins.

PMID- 21741262
TI  - Metabolism of the seed and endocarp of cherry (Prunus avium L.) during
      development.
AB  - In this study some aspects of organic and amino acid metabolism in cherry
      endocarp and seed were investigated during their development. The abundance and
      location of a number of enzymes involved in these processes were investigated.
      These enzymes were aspartate aminotransferase (AspAT; EC:2.6.1.1), glutamine
      synthetase (GS; EC:6.3.1.2), phosphoenolpyruvate carboxylase (PEPC; EC:4.1.1.31),
      phosphoenolpyruvate carboxykinase (PEPCK; EC:4.1.1.49), and ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco; EC:4.1.1.39). There was a transient
      and massive accumulation of vegetative storage proteins in the endocarp. These
      proteins were remobilised as the endocarp lignified and at the same time that
      proteins were accumulated in the seed. This raised the possibility that a
      proportion of imported amino acids were temporarily stored in the endocarp as
      protein, and that these were later utilised by the seed when it started to
      accumulate storage proteins. Rubisco was present in the embryo and integuments of
      the seed although no chlorophyll was present. This is the first time that Rubisco
      has been detected in non-green seeds. The maximum abundance of Rubisco in the
      seed coincided with the deposition of seed storage proteins. A possible function
      for Rubisco in cherry seed is discussed. PEPCK was located in the integuments and
      appeared when seed storage proteins were being accumulated. In the integuments
      and embryo AspAT, GS, PEPC and Rubisco also appeared, or greatly increased in
      abundance, when seed storage proteins were being deposited.

PMID- 21741263
TI  - Pattern of solutes accumulated during leaf osmotic adjustment as related to
      duration of water deficit for wheat at the reproductive stage.
AB  - This study examined expression of osmotic adjustment (OA) and accumulation of
      solutes in wheat (Triticum aestivum L.) leaves in response to water deficit (WD)
      imposed at the reproductive stage. Two contrasting cultivars, Hartog and Sunco
      (putatively high and low in OA capacity, respectively), were grown in deep (viz.
      80 cm) pots in a controlled environment. In a sandy substrate, leaf OA was 5
      times greater in Hartog compared with Sunco. At 21 d of WD treatment, K(+) only
      accounted for 12% of OA in Hartog and 48% in Sunco with less OA (i.e. tissue K(+)
      led to different proportions owing to different magnitudes of OA). Glycinebetaine
      and proline also increased under WD, but these were not significant osmotica on a
      whole tissue basis. Hartog accumulated dry matter faster than Sunco under WD, and
      this was consistent with greater water extraction by Hartog than by Sunco. In a
      second experiment on Hartog, with loam added to the sand to increase water
      holding capacity and thus enable a longer draw-down period, leaf OA increased to
      0.37 MPa at 37 d of withholding water. K(+) increased up to 16 d of drying and
      then decreased towards 37 d. Glycinebetaine, proline, glucose and fructose all
      increased during the draw-down period, although with different dynamics; e.g.
      glycinebetaine increased linearly whereas glucose showed an exponential increase.
      By contrast, sucrose declined. K(+) was the major contributor to OA (viz. 54%) up
      to 30 d of drying, whereas glycinebetaine, proline and glucose were major
      contributors later (at d 37 these organic solutes each accounted for 19, 21 and
      21% of OA). Thus, the various solutes that contributed to leaf OA in wheat cv.
      Hartog accumulated at different times as WD developed.

PMID- 21741264
TI  - Manifestation of an ameloblastic carcinoma ten years after follicular cyst
      enucleation in the mandibular ramus.
AB  - Ameloblastic carcinoma (AC) is a rare tumour which can emerge de novo or from an
      ameloblastoma. To our knowledge, malignant transformation from an odontogenic
      cyst into an AC has not been documented yet. This case report describes the
      manifestation of an AC 10 years after enucleation of a histologically confirmed
      follicular cyst in the angle of the mandible.

PMID- 21741265
TI  - Being shot by a bush cutter.

PMID- 21741267
TI  - Phosphodiesterase type 5 (PDE5) in the adipocyte: a novel player in fat
      metabolism?
AB  - Phosphodiesterase type 5 (PDE5) is expressed in many tissues (e.g. heart, lung,
      pancreas, penis) and plays a specific role in hydrolyzing cyclic guanosine
      monophosphate (cGMP). In adipocytes, cGMP regulates crucial functions by
      activating cGMP-dependent protein kinase (PKG). Interestingly, PDE5 was recently
      identified in adipose tissue, although its role remains unclear. Its inhibition,
      however, was recently shown to affect adipose differentiation and aromatase
      function. This review summarizes evidence supporting a role for the PDE5
      regulated cGMP/PKG system in adipose tissue and its effects on adipocyte
      function. A better elucidation of the role of PDE5 in the adipocyte could reveal
      new therapeutic strategies for fighting obesity and metabolic syndrome.

PMID- 21741268
TI  - Environmental and epigenetic effects upon preimplantation embryo metabolism and
      development.
AB  - In vitro fertilization has provided a unique window into the metabolic processes
      that drive embryonic growth and development from a fertilized ovum to a competent
      blastocyst. Post-fertilization development is dependent upon a dramatic
      reshuffling of the parental genomes during meiosis, as well as epigenetic changes
      that provide a new and autonomous set of instructions to guide cellular
      differentiation both in the embryo and beyond. Although early literature focused
      simply on the substrates and culture conditions required for progress through
      embryonic development, more recent insights lead us to suggest that the
      surrounding environment can alter the epigenome, which can, in turn, impact upon
      embryonic metabolism and developmental competence.

PMID- 21741269
TI  - Glutathione S-transferase T1 polymorphism is associated with breast cancer
      susceptibility.
AB  - The association between present/null polymorphism of glutathione S-transferase T1
      (GSTT1) and breast cancer risk are still inconclusive. We performed a meta
      analysis to derive a more precise estimation of the relationship. A total of 48
      studies including 17,254 cases and 21,163 controls were involved in this meta
      analysis. When all studies were pooled into the meta-analysis, significantly
      elevated breast cancer risk was associated with null genotype (OR=1.138, 95%
      CI=1.051-1.232). When stratified by ethnicity, significantly increased risks were
      found for Caucasians (OR=1.185, 95% CI=1.075-1.306), but no statistically
      significantly increased risks were found in Asians (OR=1.017, 95% CI=0.846-1.223)
      and Africans (OR=1.160, 95% CI=0.815-1.650). In the subgroup analysis by controls
      source, statistically significantly elevated risks were both found in population
      based studies (OR=1.123, 95% CI=1.014-1.243) and hospital-based studies
      (OR=1.181, 95% CI=1.056-1.321). When stratified by menopausal status, no
      statistically significantly increased risks were found in premenopausal women
      (OR=1.115, 95% CI=0.925-1.345) and postmenopausal women (OR=1.077, 95% CI=0.992
      1.169). In summary, this meta-analysis suggests that the GSTT1 null genotype is a
      risk allele for breast cancer development. However, large sample and
      representative population-based studies with homogeneous breast cancer patients
      and well matched controls are warranted to confirm this finding.

PMID- 21741271
TI  - Pheochromocytoma detected during anesthesia induction.

PMID- 21741270
TI  - Tolerogenic dendritic cells and their role in transplantation.
AB  - The pursuit of clinical transplant tolerance has led to enhanced understanding of
      mechanisms underlying immune regulation, including the characterization of immune
      regulatory cells, in particular antigen-presenting cells (APC) and regulatory T
      cells (Treg), that may play key roles in promoting operational tolerance.
      Dendritic cells (DC) are highly efficient APC that have been studied extensively
      in rodents and humans, and more recently in non-human primates. Owing to their
      ability to regulate both innate and adaptive immune responses, DC are considered
      to play crucial roles in directing the alloimmune response towards transplant
      tolerance or rejection. Mechanisms via which they can promote central and
      peripheral tolerance include clonal deletion, the induction of Treg, and
      inhibition of memory T cell responses. These properties have led to the use of
      tolerogenic DC as a therapeutic strategy to promote organ transplant tolerance.
      In rodents, infusion of donor- or recipient-derived tolerogenic DC can
      extensively prolong donor-specific allograft survival, in association with
      regulation of the host T cell response. In clinical transplantation, progress has
      been made in monitoring DC in relation to graft outcome, including studies in
      operational liver transplant tolerance. Although clinical trials involving
      immunotherapeutic DC for patients with cancer are ongoing, implementation of
      human DC therapy in clinical transplantation will require assessment of various
      critical issues. These include cell isolation and purification techniques,
      source, route and timing of administration, and combination immunosuppressive
      therapy. With ongoing non-human primate studies focused on DC therapy, these
      logistics can be investigated seeking the optimal approaches. The scientific
      rationale for implementation of tolerogenic DC therapy to promote clinical
      transplant tolerance is strong. Evaluation of technical and therapeutic logistic
      issues is an important next step prior to the application of tolerogenic DC in
      clinical organ transplantation.

PMID- 21741272
TI  - Hypoactive delirium after cardiac surgery as an independent risk factor for
      prolonged mechanical ventilation.
AB  - OBJECTIVE: The authors' intention was to evaluate the incidence of the three
      subtypes of delirium, the risk factors of the subtypes in cardiac surgery, and
      the impact of the subtypes on clinical outcomes. DESIGN: A prospective study.
      SETTING: A university hospital. PARTICIPANTS: A total population of 506 patients
      undergoing cardiac surgery was screened for delirium. INTERVENTIONS: None.
      MEASUREMENT AND MAIN RESULTS: Patients undergoing cardiac surgery were screened
      by using the Intensive Care Delirium Screening Checklist (ICDSC) and the Richmond
      Agitation and Sedation Scale (RASS). Patients with hypoactive delirium were
      compared with nondelirious patients. Outcomes measured were the duration of
      mechanical ventilation and the length of stay in the intensive care unit. The
      overall delirium incidence was 11.6%, whereas the incidence of the hypoactive
      subtype was 9%. Age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01
      1.09, p = 0.02), a history of depression (OR = 3.57; 95% CI, 1.04-10.74; p =
      0.03), preoperative therapy with diuretics (OR = 2.85; 95% CI, 1.36-6.35; p <
      0.01), aortic clamping times (OR = 1.01; 95% CI, 1.00-1.02; p < 0.01) and blood
      transfusions (OR = 1.18; 95% CI, 1.05-1.34; p < 0.01) were predictors for the
      development of hypoactive delirium. Preoperative therapy with beta-blockers (OR =
      0.32; 95% CI, 0.16-0.65; p < 0.01) and higher hemoglobin before surgery (OR =
      0.73; 95% CI, 0.60-0.91; p < 0.01) were associated with a lower prevalence of
      hypoactive delirium. Hypoactive delirium is an independent predictor for
      prolonged mechanical ventilation time (OR = 1.56; 95% CI, 1.25-1.92; p < 0.01)
      and the length of stay in the ICU (OR = 1.42; 95% CI, 1.22-1.65, p < 0.01).
      CONCLUSION: Hypoactive delirium itself is a strong predictor for a longer ICU
      stay and a prolonged period of mechanical ventilation. Some of the risk factors
      related to the intraoperative and postoperative setting are suitable for
      preventive action.

PMID- 21741273
TI  - On the automaticity of pure perceptual sequence learning.
AB  - We investigated the automaticity of implicit sequence learning by varying
      perceptual load in a pure perceptual sequence learning paradigm. Participants
      responded to the randomly changing identity of a target, while the irrelevant
      target location was structured. In Experiment 1, the target was presented under
      low or high perceptual load during training, whereas testing occurred without
      load. Unexpectedly, no sequence learning was observed. In Experiment 2,
      perceptual load was introduced during the test phase to determine whether load is
      required to express perceptual knowledge. Learning itself was unaffected by
      visuospatial demands, but more learning was expressed under high load test
      conditions. In Experiment 3, we demonstrated that perceptual load is not required
      for the acquisition of perceptual sequence knowledge. These findings suggest that
      perceptual load does not mediate the perceptual sequence learning process itself,
      supporting the automaticity of implicit learning, but is mandatory for the
      expression of pure perceptual sequence knowledge.

PMID- 21741274
TI  - Autopsy demonstration of intramyocardial polymer gel emboli associated with a
      giant-cell reaction following cardiac catheterization: a case report.
AB  - BACKGROUND: Foreign body type granulomatous vasculitis has been reported in blood
      vessels of the brain, lungs, and skin of the foot following intravascular
      instrumentation with devices coated with hydrophilic polymer gel. We report a
      case of intramyocardial polymer gel emboli associated with granulomatous
      vasculitis following cardiac catheterization. METHOD: Autopsy observations in a
      77-year-old woman are presented. The patient experienced an acute myocardial
      infarction requiring catheterization and coronary stenting. The patient returned
      with a pseudoaneurysm at the site of catheterization and shortly after suffered a
      fatal arrhythmia. RESULTS: Microscopically, multiple small vessels within the
      myocardium were noted to contain a basophilic, amorphous, focally lamellated,
      focally granular material. A granulomatous inflammatory response was noted in the
      vessels containing the foreign material. CONCLUSIONS: Our case is the first to
      our knowledge to document intramyocardial vessel gel emboli following a cardiac
      catheterization with stenting. Although the microscopic finding of emboli within
      vessels does not seem to be the immediate cause of death in our case, it is
      highly possible that it contributed to the patient's demise.

PMID- 21741275
TI  - Epilepsy surgery in children with developmental tumours.
AB  - We report our experience regarding evaluation, surgical treatment and outcomes in
      a population of 21 children with histopathologically confirmed developmental
      tumours [nine dysembryoplastic neuroepithelial tumours (DNET), ten gangliogliomas
      (GG) and two gangliocytomas (GC)] and related epilepsy, analyzing video-EEG, MRI
      and neuropsychological data, before and after surgery. Most children had focal
      epilepsy correlating well with lesion location. One patient had epileptic spasms
      and generalized discharges. Tumours were located in the temporal lobe in 13
      patients. Mean age at surgery was 11.16 years. Postsurgical MRI showed residual
      tumour growth in one DNET. One child had a recurrent ganglioglioma with
      anaplastic transformation. At latest follow-up (mean 4.68 years) 95.2% of
      patients were seizure-free and no significant neuropsychological declines were
      observed. Evidence from our study suggests that, in this setting, surgery should
      be performed before criteria for refractory epilepsy are met, particularly in
      cases with early seizure onset, in order to optimize cognitive outcome.

PMID- 21741276
TI  - Long-term outcome of epilepsy in Kabuki syndrome.
AB  - PURPOSES AND METHODS: Kabuki syndrome (KS) is a rare dysmorphic disorder
      characterized by multiple congenital anomalies and mental retardation. Although
      epilepsy is one of the most common clinical complications associated with KS, few
      studies have evaluated its electroclinical aspects and long-term outcome.
      Therefore, we describe here a clinical series of 10 Caucasian KS patients who
      developed epilepsy in childhood. We followed all children for at least 5 years.
      RESULTS: All patients presented partial seizures and interictal EEGs revealed
      focal epileptic paroxysms with prevalent involvement of temporo-occipital areas.
      Seven children had no central nervous system abnormalities, but enlargement of
      lateral ventricles, corpus callosum hypoplasia, and adenohypophysis hypoplasia
      were revealed in three. Although antiepileptic drug (AED) treatment was effective
      in controlling seizures and normalizing EEG abnormalities in 8 patients, the
      other 2 cases were resistant to multiple AEDs. In one of these two patients,
      withdrawal of AED resulted in status epilepticus and death. CONCLUSIONS: Partial
      seizures and temporo-occipital abnormalities on interictal EEG are common
      features of KS patients who suffer from epilepsy. Prognosis of this epilepsy is
      favourable in the majority of cases with complete disappearance of seizures and
      EEG abnormalities.

PMID- 21741277
TI  - Depression and anxiety in childhood epilepsy: a review.
AB  - Population based studies suggest that symptoms of depression and anxiety are more
      frequent in children and adolescents with epilepsy compared with the general
      population. In terms of the manifestations of symptoms of depression and anxiety,
      there would appear to some symptoms unique to epilepsy in that they are
      associated with seizures and/or antiepileptic medications but these idiosyncratic
      symptoms remain under reported and have not been extensively studied. In terms of
      correlates of significant symptoms of depression and anxiety in children with
      epilepsy, some reports indicate that seizure variables (e.g., seizure frequency)
      and use of polytherapy are associated with increases in symptoms whereas other
      studies have not found this relationship. Child and family attitude/adaptation to
      epilepsy may also be risk factors for depression and anxiety but more research is
      needed in this area. The assessment of symptoms of depression and anxiety in
      children with epilepsy can be challenging given the possible role of seizures and
      AEDs, and comprehensive assessment will involve the use of screening measures,
      diagnostic interviews and a consideration of epilepsy specific factors. There
      have been few studies carried out with respect to the treatment of symptoms and
      depression and anxiety in children and adolescents with epilepsy. There is a
      significant need for a greater understanding of the nature of symptoms of
      depression and anxiety in children with epilepsy to inform treatment decisions.
      While treatment of epilepsy specific symptoms of depression and anxiety may
      involve an evaluation of the current epilepsy treatment protocols, there may also
      be a need for pharmacological and/or psychotherapeutic interventions in the
      treatment of symptoms of depression and anxiety which are not epilepsy specific.

PMID- 21741278
TI  - Final results of the prospective European trial of the Endurant stent graft for
      endovascular abdominal aortic aneurysm repair.
AB  - OBJECTIVES: The Endurant Stent Graft System (Medtronic Vascular, Santa Rosa, CA)
      is specifically designed to treat patients with abdominal aortic aneurysm,
      including those with difficult anatomies. This is the 1-year report of a
      prospective, non-randomised, open-label trial at 10 European centres. METHODS:
      Between November 2007 and August 2008, 80 patients were enrolled for elective
      endovascular aneurysm repair (EVAR) with the Endurant; 71 with moderate (<= 60
      degrees ) and nine with high (60-75 degrees ) infrarenal aortic neck angulation.
      Safety and stent-graft performance were assessed throughout a 1-year follow-up
      period. RESULTS: The device was successfully delivered and deployed in all cases.
      All-cause mortality was 5% (4/80), with one possibly device-related death.
      Serious adverse events were comparable between the high and moderate angulation
      groups. There were no device migrations, stent fractures, aortic ruptures or
      conversions to open repair. Maximal aneurysm diameter decreased >5 mm in 42.7% of
      cases. A total of 28 endoleaks were observed (26 type II, two undetermined).
      Three secondary endovascular procedures were performed for outflow vessel
      stenosis, graft limb occlusion and iliac extension, resulting in a secondary
      patency rate of 100%. No re-interventions were required in the high angulation
      group. CONCLUSIONS: The Endurant Stent Graft was successfully delivered and
      deployed in all cases and performed safely and effectively in all patients,
      including those with unfavourable proximal neck anatomy.

PMID- 21741279
TI  - Correlations between clinical variables and gene-expression profiles in carotid
      plaque instability.
AB  - OBJECTIVE: Strokes, a major cause of disability, are often caused by embolism
      from unstable carotid plaques. The aim of this study was to validate a biobank of
      human carotid endarterectomies as a platform for further exploration of pathways
      for plaque instability. For this purpose, we investigated the relationship
      between clinical parameters of plaque instability and expression of genes
      previously shown to be associated with either plaque instability or healing
      processes in the vessel wall. METHODS: A database of clinical information and
      gene-expression microarray data from 106 carotid endarterectomies were used.
      RESULTS: Expression of matrix metalloproteinase (MMP)-9 and MMP-7 was 100-fold
      higher in plaques than in normal artery. In general, genes associated with
      inflammation (such as RANKL and CD68) were overexpressed in symptomatic compared
      with asymptomatic plaques. Plaques obtained from patients undergoing surgery
      within 2 weeks after an embolic event showed up-regulation of genes involved in
      healing reactions in the vessel wall (including elastin and collagen). Statin
      treatment, as well as echodense lesions, were associated with a more stable
      phenotype. CONCLUSION: Here, we demonstrate that gene-expression profiles reflect
      clinical parameters. Our results suggest that microarray technology and clinical
      variables can be used for the future identification of central molecular pathways
      in plaque instability.

PMID- 21741280
TI  - Comments regarding 'Local anaesthesia for endovascular repair of infra-renal
      aortic aneurysms'.

PMID- 21741281
TI  - Comments regarding 'Implications of attendance patterns in Northern Ireland for
      abdominal aortic aneurysm screening'.

PMID- 21741282
TI  - A genealogical survey of Australian registered dog breeds.
AB  - Breeding practices were analysed for 32 registered dog breeds representing very
      small registries (120 Central Asian shepherd dogs) through to very large
      registries (252,521 German shepherd dogs) in Australia. The vast majority (91%)
      of registered kennels in Australia that were sampled did not regularly employ
      either close breeding or popular sire usage in their kennels and the weighted
      mean inbreeding coefficient of Australian pedigree dogs was <5%. Australian breed
      mean inbreeding coefficients ranged from 0% (Central Asian shepherd dog) to 10.1%
      (Bichon Frise). Breed effective population sizes ranged from 26 (Ibizan hound) to
      1090 (Golden retriever), comparable with other species of domesticated animals.
      The relatively low levels of inbreeding suggest that pedigree dog disorders are
      unlikely to arise frequently from the use of popular sires or close breeding in
      Australian registered dog breeds. It is possible that deleterious allele fixation
      might be driven by founder effects, genetic drift or adverse selection practices,
      which were not assessed in this analysis. European popular sire definitions
      should be revisited for rare breeds.

PMID- 21741284
TI  - Evaluation of the field efficacy of an avirulent live Lawsonia intracellularis
      vaccine in foals.
AB  - Equine proliferative enteropathy caused by Lawsonia intracellularis is an
      emerging disease with as yet unaddressed preventative measures. The hypothesis of
      this study was that vaccination will prevent clinical and sub-clinical disease.
      Weanling Thoroughbreds (n=202) from Central Kentucky were randomly assigned into
      two groups (vaccinated and non-vaccinated). Vaccinated foals received 30 mL of an
      avirulent, live L. intracellularis vaccine intra-rectally twice, 30 days apart.
      Foals were monitored for clinical disease, total solids and average weight gain
      until yearling age. There was an overall decreased disease incidence on the farms
      involved in the study that did not differ significantly between the groups. This
      decreased disease prevalence in the study population may be associated with the
      ongoing vaccine trial on these farms, as disease prevalence in Central Kentucky
      did not change in 2009 compared to 2008.

PMID- 21741283
TI  - Expanded dog leukocyte antigen (DLA) single nucleotide polymorphism (SNP)
      genotyping reveals spurious class II associations.
AB  - The dog leukocyte antigen (DLA) system contains many of the functional genes of
      the immune system, thereby making it a candidate region for involvement in immune
      mediated disorders. A number of studies have identified associations between
      specific DLA class II haplotypes and canine immune hemolytic anemia, thyroiditis,
      immune polyarthritis, type I diabetes mellitus, hypoadrenocorticism, systemic
      lupus erythematosus-related disease complex, necrotizing meningoencephalitis
      (NME) and anal furunculosis. These studies have relied on sequencing
      approximately 300 bases of exon 2 of each of the DLA class II genes: DLA-DRB1,
      DLA-DQA1 and DLA-DQB1. In the present study, an association (odds ratio=4.29) was
      identified by this method between Weimaraner dogs with hypertrophic
      osteodystrophy (HOD) and DLA-DRB1*01501. To fine map the association with HOD, a
      genotyping assay of 126 coding single nucleotide polymorphisms (SNPs) from across
      the entire DLA, spanning a region of 2.5 Mb (3,320,000-5,830,000) on CFA12, was
      developed and tested on Weimaraners with HOD, as well as two additional breeds
      with diseases associated with DLA class II: Nova Scotia duck tolling retrievers
      with hypoadrenocorticism and Pug dogs with NME. No significant associations were
      found between Weimaraners with HOD or Nova Scotia duck tolling retrievers with
      hypoadrenocorticism and SNPs spanning the DLA region. In contrast, significant
      associations were found with NME in Pug dogs, although the associated region
      extended beyond the class II genes. By including a larger number of genes from a
      larger genomic region, a SNP genotyping assay was generated that provides
      coverage of the extended DLA region and may be useful in identifying and fine
      mapping DLA associations in dogs.

PMID- 21741285
TI  - Complex molecular dynamics of (CH3NH3)5Bi2Br11 (MAPBB) protons from NMR
      relaxation and second moment of NMR spectrum.
AB  - Molecular dynamics of a polycrystalline sample of (CH(3)NH(3))(5)Bi(2)Br(11)
      (MAPBB) is studied on the basis of the proton T(1) (55.2 MHz) relaxation time and
      the proton second moment of NMR line. The T(1) (55.2 MHz) was measured for
      temperatures from 20K to 330 K, while the second moment M(2) for those from 40K
      to 330 K. The proton spin pairs of the methyl and ammonium groups perform a
      complex stochastic motion being a resultant of four components characterised by
      the correlation times tau(3)(T), tau(3)(H), tau(2), and tau(iso), referring to
      the tunnelling and over the barrier jumps in a triple potential, jumps between
      two equilibrium sites and isotropic rotation. The theoretical expressions for the
      spectral densities in the cases of the complex motion considered were derived.
      For tau(3)(H), tau(2), and tau(iso) the Arrhenius temperature dependence was
      assumed, while for tau(3)(T)-the Schrodinger one. The correlation times tau(3)(H)
      for CH(3) and NH(3) groups differ, which indicates the uncorrelated motion of
      these groups. The stochastic tunnelling jumps are not present above the
      temperature T(tun) at which the thermal energy is higher than the activation
      energy of jumps over the barrier attributed to the hindered rotation of the CH(3)
      and NH(3) groups. The T(tun) temperature is 54.6 K for NH(3) group and 46.5 K for
      CH(3) group in MAPBB crystal. The tunnelling jumps of the methyl and ammonium
      protons are responsible for the flattening of T(1) temperature dependence at low
      temperatures. The isotropic tumbling is detectable only from the M(2) temperature
      dependence. The isotropic tumbling reduces the second moment to 4 G(2) which is
      the value of the intermolecular part of the second moment. The motion
      characterised by the correlation time tau(2) is well detectable from both T(1)
      and M(2) temperature dependences. This motion causes the appearance of T(1)
      minimum at 130 K and reduction of the second moment to the 7.7 G(2) value. The
      small tunnelling splitting omega(T) of the same value for the methyl and ammonium
      groups was estimated as 226 MHz from the Haupt equation or 80 MHz from the
      corrected by us Haupt equation. These frequencies correspond to 0.93 MUeV and
      0.34 MUeV tunnel splitting energy.

PMID- 21741286
TI  - Structure determination in "shiftless" solid state NMR of oriented protein
      samples.
AB  - An efficient formalism for calculating protein structures from oriented-sample
      NMR data in the torsion-angle space is presented. Angular anisotropies of the NMR
      observables are treated by utilizing an irreducible spherical basis of rotations.
      An intermediate rotational transformation is introduced that greatly speeds up
      structural fitting by rendering the dependence on the torsion angles Phi and Psi
      in a purely diagonal form. Back-calculation of the simulated solid-state NMR
      spectra of protein G involving 15N chemical shift anisotropy (CSA), and 1H-15N
      and 1Halpha-13Calpha dipolar couplings was performed by taking into account non
      planarity of the peptide linkages and experimental uncertainty. Even a relatively
      small (to within 1 ppm) random variation in the CSA values arising from
      uncertainties in the tensor parameters yields the RMSD's of the back-calculated
      structures of more than 10 A. Therefore, the 15N CSA has been substituted with
      heteronuclear dipolar couplings which are derived from the highly conserved bond
      lengths and bond angles associated with the amino-acid covalent geometry. Using
      the additional 13Calpha-15N and 13C'-15N dipolar couplings makes it possible to
      calculate protein structures entirely from "shiftless" solid-state NMR data. With
      the simulated "experimental" uncertainty of 15 Hz for protein G and 120 Hz for a
      helical hairpin derived from bacteriorhodopsin, back-calculation of the synthetic
      dipolar NMR spectra yielded a converged set of solutions. The use of distance
      restraints dramatically improves structural convergence even if larger
      experimental uncertainties are assumed.

PMID- 21741287
TI  - [Helical tomotherapy for axial and paraspinal tumours: experience of Institut
      Bergonie (14 cases)].
AB  - PURPOSE: To evaluate the feasibility of helical tomotherapy intensity-modulated
      radiotherapy for the treatment of axial and paraspinal tumours. PATIENTS AND
      METHODS: Fourteen consecutive patients with axial and paraspinal tumours at the
      Bergonie Institute between June 2007 and June 2009 were analysed. Various
      localisations were observed: four paravertebral tumours, five primitive vertebral
      tumours and six iliosacral or sacral tumours. RESULTS: The dose prescribed to the
      median of the planning target volume (PTV) varied from 45 to 68Gy depending on
      histology. The maximum dose delivered to the PTV (Dnear max or D2%) was 60.6Gy
      (range 46.3-69.1). In the five cases where the tumour was located close to the
      spinal cord, the median value of Dnear max was 40.1Gy (range 37.8-45.4). In the
      seven where the tumour was situated close to the cauda equina, the median value
      of Dnear max was 46.5Gy (range 39.2-60). For two cases in whom the sciatic nerve
      was the nervous structure at risk, the Dnear max was 64.4 and 67Gy. Six patients
      were in complete remission, six patients suffered a relapse at a median follow-up
      of 14.5 months (4-24), two died following local tumour progression and
      metastasis, tumoral stabilisation had been obtained in two patients. Treatment
      was well tolerated and was never interrupted in all patients. CONCLUSIONS:
      Results from this preliminary series are encouraging, particularly concerning the
      good tolerance of this new intensity-modulated radiotherapy presently more
      available than proton therapy.

PMID- 21741288
TI  - Ultrasound promoted Wurtz coupling of alkyl bromides and dibromides.
AB  - Sonochemically enhanced Wurtz coupling using lithium metal has been investigated
      for a number of isomeric alkyl bromides under a variety conditions. The products
      result from direct coupling of short lived radicals formed at the metal surface
      rather than the secondary radicals which can be formed during coupling of
      aromatic halides and thus give rise to a single major product. Coupling has been
      extended to dibrominated aryl and alkyl compounds as well as showing that aryl
      alkyl coupling is possible. Dibrominated alkyls were found to give low molecular
      weight oligomers although no reaction occurred for 1,2-isomers. The growth of
      oligomers in THF may be solubility limited. A simple model is proposed to explain
      these findings.

PMID- 21741289
TI  - Biomechanical evaluation of proximal tibial behavior following unicondylar knee
      arthroplasty: modified resected surface with corresponding surgical technique.
AB  - Persistent pain and periprosthetic fracture of the proximal tibia are troublesome
      complications in modern unicondylar knee arthroplasty (UKA). Surgical errors and
      acute corners on the resected surface can place excessive strains on the bone,
      leading to bone degeneration. This study attempted to lower strains by altering
      the orthogonal geometry and avoiding extended vertical saw cuts. Finite element
      models were utilized to predict biomechanical behavior and were subsequently
      compared against experimental data. On the resected surface of the extended saw
      cut model, the greatest strains showed a 50% increase over a standard implant;
      conversely, the strains decreased by 40% for the radial-corner shaped model. For
      all UKA models, the peak strains below the resection level increased by 40%
      relative to an intact tibia. There was no significant difference among the
      implanted models. This study demonstrated that a large increase in strains arises
      on the tibial plateau to resist a cantilever-like bending moment following UKA.
      Surgical errors generally weaken the tibial support and increase the risk of
      fractures. This study provides guidance on altering the orthogonal geometry into
      a radial-shape to reduce strains and avoid degenerative remodeling. Furthermore,
      it could be expected that predrilling a posteriorly sloped tunnel through the
      tibia prior to cutting could achieve greater accuracy in surgical preparations.

PMID- 21741290
TI  - Writing through a robot: a proof of concept for a brain-machine interface.
AB  - This paper describes a non-invasive human brain-actuated robotic arm experiment,
      which allows remote writing. In the local environment, the participant decides on
      an arbitrary word to transmit. A mental speller interface is then used to select
      the letters. A robot arm placed in the remote environment writes the word on a
      whiteboard in real time. A multidisciplinary framework such as the one presented
      here exemplifies a class of interactive applications with possible relevance in a
      variety of fields, such as entertainment and clinical environments.

PMID- 21741291
TI  - Computation of realistic virtual phantom images for an objective lesion
      detectability assessment in digital mammography.
AB  - Image quality assessment is required for an optimal use of mammographic units. On
      the one hand, there are objective image quality assessment methods based on the
      measurement of technical parameters such as modulation transfer function (MTF),
      noise power spectrum (NPS) or detection quantum efficiency (DQE) describing
      performances of digital detectors. These parameters are, however, without direct
      relationship with lesion detectability in clinical practice. On the other hand,
      there are image quality assessment methods involving time consuming procedures,
      but presenting a direct relationship with lesion detectability. This contribution
      describes an X-ray source/digital detector model leading to the simulation of
      virtual contrast-detail phantom (CDMAM) images. The virtual image computation
      method requires the acquisition of only few real images and allows for an
      objective image quality assessment presenting a direct relationship with lesion
      detectability. The transfer function of the proposed model takes as input
      physical parameters (MTF* and noise) measured under clinical conditions on
      mammographic units. As presented in this contribution, MTF* is a modified MTF
      taking into account the effects due to X-ray scatter in the breast and
      magnification. Results obtained with the structural similarity index prove that
      the simulated images are quite realistic in terms of contrast and noise. Tests
      using contrast detail curves highlight the fact that the simulated and real
      images lead to very similar data quality in terms of lesion detectability.
      Finally, various statistical tests show that quality factors computed for both
      the simulated images and the real images are very close for the two data sets.

PMID- 21741292
TI  - Risk factors for prolonged hemichorea-hemiballism caused by hyperglycemia.

PMID- 21741293
TI  - Screening of 10 SNPs of LINGO1 gene in patients with essential tremor in the
      Latvian population.

PMID- 21741294
TI  - Cytokine expression and microglial activation in progressive supranuclear palsy.
AB  - Although little is known about the etiology of progressive supranuclear palsy
      (PSP), genetic and epigenetic factors, oxidative injury and inflammation are
      thought to contribute to its development and/or progression. Evidence for
      activated glia involvement in PSP has raised the possibility that
      neuroinflammation may contribute to its pathogenesis. To investigate the
      correlation between neuroinflammation and PSP, a comparative study was conducted
      on the patterns of cytokine expression in different regions of the brains of PSP,
      Alzheimer's disease (AD) patients and normal controls. Our results show different
      patterns of cytokine expression in each disease, with the expression of IL-1beta
      transcripts being significantly higher in the substantia nigra of PSP than in AD
      and controls, while AD brains had significantly higher IL-1beta expression in the
      parietal cortex compared to PSP and controls. In addition, expression of TGFbeta
      was significantly higher in the cortical areas (particularly frontal and parietal
      lobes) of AD compared to PSP and controls. These results show a disease-specific
      topographical relationship among the expression of certain cytokines (IL-1beta
      and TGFbeta), microglial activation and neurodegenerative changes, suggesting
      that these cytokines may contribute to the pathologic process. If so, the use of
      cytokine-inhibitors and/or other anti-inflammatory agents may be able to slow
      disease progression in PSP.

PMID- 21741295
TI  - A multilevel analysis of the determinants and cross-national variations of HIV
      seropositivity in sub-Saharan Africa: evidence from the DHS.
AB  - This paper applies multilevel logistic regression models to Demographic and
      Health Survey data collected during 2003-2008 from 20 countries of sub-Saharan
      Africa to examine the determinants and cross-national variations in the risk of
      HIV seropositivity in the region. The models include individual-level and
      contextual region/country-level risk factors. Simultaneous confidence intervals
      of country-level residuals are used to compare the risk of being HIV seropositive
      across countries. The study reveals interesting general patterns in the risk of
      HIV seropositivity in sub-Saharan Africa. In particular, the findings highlight
      the gender disparity in socio-economic risk factors, partly explained by sexual
      behaviour factors.

PMID- 21741296
TI  - Ability of patients to recall habitual contact lens products and enhancement of
      recall using photographic aids.
AB  - PURPOSE: To determine the proportion of soft contact lens (CL) wearers who are
      able to recall their habitual products (lenses and care system) correctly from
      memory, and to evaluate the value of using photographic aids (PAs) to improve
      recall. METHODS: 103 soft lens wearers attended 2 visits to investigate their
      habitual CL product use. At the first visit they were asked to recall which
      products they were using and then to identify their products from PAs. They
      returned for a second visit with their products for confirmation. RESULTS: 51%
      correctly reported their lens brands from memory alone, which improved to 87%
      with the use of the PAs (p<0.001). 41% correctly reported their habitual care
      system from memory alone, which improved to 80% with the use of PAs (p<0.001).
      Females were better at recalling care system brand names than males (49% versus
      27% correct, p=0.040) and wearers with more than 1 year experience with their
      habitual CLs had better recall than those with up to 1 year experience (63%
      versus 27%, p=0.014). CONCLUSION: Less than 50% of contact lens wearers were able
      to recall the names of their habitual lens and lens care products correctly from
      memory. PAs improved this recall significantly for both contact lenses and
      contact lens care systems.

PMID- 21741297
TI  - The broad spectrum of plant associations with other organisms.

PMID- 21741298
TI  - Diorganotin(IV) complexes of biologically potent 4(3H)-quinazolinone derived
      Schiff bases: synthesis, spectroscopic characterization, DNA interaction studies
      and antimicrobial activity.
AB  - Four Schiff base ligands and their corresponding organotin(IV) complexes have
      been synthesized and characterized by elemental analyses, IR, (1)H NMR, MS and
      thermal studies. The Schiff bases are obtained by the condensation of 3-amino-2
      methyl-4(3H)-quinazolinone with different substituted aldehydes. The elemental
      analysis data suggest the stoichiometry to be 1:1 ratio formation. Infrared
      spectral data agreed with the coordination to the central metal ion through imine
      nitrogen, lactam oxygen and deprotonated phenolic oxygen atoms. All the
      synthesized compounds have been evaluated for antimicrobial activity against
      selected species of microorganisms. In addition, DNA binding/cleavage capacity of
      the compounds was analyzed by absorption spectroscopy, viscosity measurements and
      gel electrophoresis methods.

PMID- 21741299
TI  - Comparison of direct fluorescent antibody staining and real-time reverse
      transcriptase PCR for the detection of novel 2009 influenza A (H1N1) in
      nasopharyngeal samples.

PMID- 21741300
TI  - Optimising PCR reactions; remember magnesium?

PMID- 21741301
TI  - Effect of median-nerve electrical stimulation on BOLD activity in acute ischemic
      stroke patients.
AB  - OBJECTIVE: To investigate blood oxygenation level-dependent (BOLD) activation
      during somatosensory electrical stimulation of the median nerve in acute stroke
      patients and to determine its correlation with ischemic damage and clinical
      recovery over time. METHODS: Fourteen acute stroke patients underwent functional
      magnetic resonance imaging (fMRI) during contralesional median-nerve electrical
      stimulation 12-48 h after stroke. Findings were then validated by diffusion
      tensor imaging (DTI) and motor evoked potential by transcranial magnetic
      stimulation (TMS). RESULTS: Poor clinical recovery at three months was noted in
      four patients with no activation in the early days after stroke, whereas good
      clinical recovery was observed in eight patients with a normal activation pattern
      in the primary sensory motor area in the acute phase. In two patients BOLD
      activation correlated weakly with clinical recovery. Findings from TMS and DTI
      partially correlated with clinical recovery and functional scores. CONCLUSIONS:
      Clinically relevant insights into the "functional reserve" of stroke patients
      gained with peripheral nerve stimulation during fMRI may carry prognostic value
      already in the acute period of a cerebrovascular accident. SIGNIFICANCE: BOLD
      activation maps could provide insights into the functional organization of the
      residual systems and could contribute to medical decision making in neurological
      and rehabilitative treatment.

PMID- 21741302
TI  - Effects of mobile phone signals over BOLD response while performing a cognitive
      task.
AB  - OBJECTIVE: The aim of this study was to investigate the effects induced by an
      exposure to a GSM signal (Global System for Mobile Communication) on brain BOLD
      (blood-oxygen-level dependent) response, as well as its time course while
      performing a Go-NoGo task. METHODS: Participants were tested twice, once in
      presence of a "real" exposure to GSM radiofrequency signal and once under a
      "sham" exposure (placebo condition). BOLD response of active brain areas and
      reaction times (RTs) while performing the task were measured both before and
      after the exposure. RESULTS: RTs to the somatosensory task did not change as a
      function of exposure (real vs sham) to GSM signal. BOLD results revealed
      significant activations in inferior parietal lobule, insula, precentral and
      postcentral gyri associated with Go responses after both ''real'' and ''sham''
      exposure, whereas no significant effects were observed in the ROI analysis.
      CONCLUSIONS: The present fMRI study did not detect any brain activity changes by
      mobile phones. Also RTs in a somatosensory task resulted unaffected.
      SIGNIFICANCE: No changes in BOLD response have been observed as a consequence of
      RF-EMFs exposure.

PMID- 21741303
TI  - Cognition and event-related potentials in adult-onset non-demented myotonic
      dystrophy type 1.
AB  - OBJECTIVE: To clarify the cognitive and event-related potentials (ERPs) profiles
      of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1).
      METHODS: Fourteen DM1 patients and matched 14 normal controls were enrolled. DM1
      patients were compared with normal controls, using a variety of
      neuropsychological tests; an auditory "oddball" counting paradigm for the ERPs,
      and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs
      and neuropsychological parameters were correlated with CTG repeat size, duration
      of illness, grip strength, and arterial blood gas analysis. RESULTS: Frontal lobe
      dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed
      in DM1. Longer CTG repeat size was associated with fewer categories achieved on
      Wisconsin Card Sorting Test. Greater grip strength was associated with better
      scores on color-word "interference" of Stroop test. P3 latency was negatively
      correlated with PaO(2). LORETA revealed significant hypoactivities at the
      orbitofrontal and medial temporal lobe, cingulate, and insula. There was no
      correlation between ERPs and CTG expansion. CONCLUSIONS: Adult-onset non-demented
      DM1 presented frontal lobe dysfunction. Absence of correlations between CTG
      repeat size and objective ERP parameters suggested CTG expansion in lymphocytes
      does not directly contribute to cognitive dysfunction. SIGNIFICANCE: CTG
      expansion in lymphocytes does not directly contribute to cognitive dysfunction of
      adult-onset non-demented DM1.

PMID- 21741304
TI  - Characterization of spatial cell distribution in multilayer sheet of human
      keratinocytes through a stereoscopic cell imaging system.
AB  - A novel system was developed to characterize the spatial distribution of human
      keratinocytes in cultured epithelial sheet, based on stereoscopic observation of
      nuclei using a confocal laser microscope in combination with image processing.
      The presented technique allowed understanding of the proliferative and growth
      arrested states of cells in multilayered sheet.

PMID- 21741305
TI  - TLR ligands of Lactobacillus sakei LK-117 isolated from seed mash for brewing
      sake are potent inducers of IL-12.
AB  - Many studies have investigated the immunostimulatory effects of bacteria, such as
      the anti-allergic effects of lactic acid bacteria (LAB) and LAB-fermented milk.
      Importantly, these anti-allergic effects have been observed for both viable and
      nonviable bacteria. However, there are no reported immunological effects of LAB
      isolated from kimoto, the traditional yeast starter culture used for brewing
      sake, which also involves spontaneous lactate fermentation. In this study, we
      determined whether the Leuconostoc mesenteroides and Lactobacillus sakei
      bacterial strains obtained from kimoto affected the production of interleukin-12
      (IL-12), an inducer of the T-helper type-1 immune response. By incubating
      autoclaved bacteria with J774.1 macrophage-like cells, we found that L. sakei LK
      117 induced a sustained increase in IL-12p40 production. The IL-12-inducing
      ability of LK-117 was unaffected by anti-TLR2 neutralization and was entirely
      inhibited when the LK-117 cells were treated with RNase. When LK-117 cells were
      treated with M-1, an N-acetylmuramidase, at varying concentrations and for
      different periods of time, the ability of the bacteria to induce IL-12 decreased
      quickly. Although an active fraction could be prepared by chromatography from the
      soluble products of enzymolysis, the fraction's induction ability was <2% of that
      of intact organisms, and induction ability disappeared completely upon anti-TLR2
      neutralization after treating the active fraction with RNase. These results
      suggest that single-stranded RNA released from cells that were disrupted by
      autoclaving might act as a TLR ligand and provide a novel mechanism in which heat
      killed LAB could be used to regulate immune activity.

PMID- 21741306
TI  - An assessment of vertical inheritance versus endosymbiont transfer of nucleus
      encoded genes for mitochondrial proteins following tertiary endosymbiosis in
      Karlodinium micrum.
AB  - Most photosynthetic dinoflagellates harbour a red alga-derived secondary plastid.
      In the dinoflagellate Karlodinium micrum, this plastid was replaced by a
      subsequent endosymbiosis, resulting in a tertiary plastid derived from a
      haptophyte. Evolution of endosymbionts entails substantial relocation of
      endosymbiont genes to the host nucleus: a process called endosymbiotic gene
      transfer (EGT). In K. micrum, numerous plastid genes from the haptophyte nucleus
      are found in the host nucleus, providing evidence for EGT in this system. In
      other cases of endosymbiosis, notably ancient primary endosymbiotic events, EGT
      has been inferred to contribute to remodeling of other cell functions by
      expression of proteins in compartments other than the endosymbiont from which
      they derived. K. micrum provides a more recently derived endosymbiotic system to
      test for evidence of EGT and gain of function in non-plastid compartments. In
      this study, we test for gain of haptophyte-derived proteins for mitochondrial
      function in K. micrum. Using molecular phylogenies we have analysed whether
      nucleus-encoded mitochondrial proteins were inherited by EGT from the haptophyte
      endosymbiont, or vertically inherited from the dinoflagellate host lineage. From
      this dataset we found no evidence of haptophyte-derived mitochondrial genes, and
      the only cases of non-vertical inheritance were genes derived from lateral gene
      transfer events.

PMID- 21741307
TI  - Polypharmacy in elderly patients with cancer: clinical implications and
      management.
AB  - More and more elderly people with cancer are treated in oncology clinics
      worldwide every year, many of whom have comorbid disorders treated with one or
      more drugs. Moreover, these patients might also take self-prescribed over-the
      counter drugs or complementary and alternative medicines, which they might not
      tell their doctor about. Initiation of chemotherapy with one or more cytotoxic or
      targeted agents and drugs for treatment of cancer symptoms or toxic effects
      related to treatment can result in polypharmacy. We examine the clinical
      implications of polypharmacy. Challenges for the medical teams who treat elderly
      patients with cancer include identification of what drugs are actually being
      taken by the patient, avoidance or management of any adverse effects or drug
      interactions, and reassessing the patient's overall treatment. We address these
      issues and propose practical recommendations for management of treatment for
      elderly patients with cancer.

PMID- 21741308
TI  - Dignity therapy for patients who are terminally ill.

PMID- 21741309
TI  - Effect of dignity therapy on distress and end-of-life experience in terminally
      ill patients: a randomised controlled trial.
AB  - BACKGROUND: Dignity therapy is a unique, individualised, short-term psychotherapy
      that was developed for patients (and their families) living with life-threatening
      or life-limiting illness. We investigated whether dignity therapy could mitigate
      distress or bolster the experience in patients nearing the end of their lives.
      METHODS: Patients (aged >=18 years) with a terminal prognosis (life expectancy
      <=6 months) who were receiving palliative care in a hospital or community setting
      (hospice or home) in Canada, USA, and Australia were randomly assigned to dignity
      therapy, client-centred care, or standard palliative care in a 1:1:1 ratio.
      Randomisation was by use of a computer-generated table of random numbers in
      blocks of 30. Allocation concealment was by use of opaque sealed envelopes. The
      primary outcomes--reductions in various dimensions of distress before and after
      completion of the study--were measured with the Functional Assessment of Chronic
      Illness Therapy Spiritual Well-Being Scale, Patient Dignity Inventory, Hospital
      Anxiety and Depression Scale, items from the Structured Interview for Symptoms
      and Concerns, Quality of Life Scale, and modified Edmonton Symptom Assessment
      Scale. Secondary outcomes of self-reported end-of-life experiences were assessed
      in a survey that was undertaken after the completion of the study. Outcomes were
      assessed by research staff with whom the participant had no previous contact to
      avoid any possible response bias or contamination. Analyses were done on all
      patients with available data at baseline and at the end of the study
      intervention. This study is registered with ClinicalTrials.gov, number
      NCT00133965. FINDINGS: 165 of 441 patients were assigned to dignity therapy, 140
      standard palliative care, and 136 client-centred care. 108, 111, and 107
      patients, respectively, were analysed. No significant differences were noted in
      the distress levels before and after completion of the study in the three groups.
      For the secondary outcomes, patients reported that dignity therapy was
      significantly more likely than the other two interventions to have been helpful
      (chi(2)=35.50, df=2; p<0.0001), improve quality of life (chi(2)=14.52; p=0.001),
      increase sense of dignity (chi(2)=12.66; p=0.002), change how their family saw
      and appreciated them (chi(2)=33.81; p<0.0001), and be helpful to their family
      (chi(2)=33.86; p<0.0001). Dignity therapy was significantly better than client
      centred care in improving spiritual wellbeing (chi(2)=10.35; p=0.006), and was
      significantly better than standard palliative care in terms of lessening sadness
      or depression (chi(2)=9.38; p=0.009); significantly more patients who had
      received dignity therapy reported that the study group had been satisfactory,
      compared with those who received standard palliative care (chi(2)=29.58;
      p<0.0001). INTERPRETATION: Although the ability of dignity therapy to mitigate
      outright distress, such as depression, desire for death or suicidality, has yet
      to be proven, its benefits in terms of self-reported end-of-life experiences
      support its clinical application for patients nearing death. FUNDING: National
      Cancer Institute, National Institutes of Health.

PMID- 21741310
TI  - The role of TLRs in neutrophil activation.
AB  - Neutrophils are key innate immune effector cells that are rapidly recruited to
      sites of infection and inflammation to provide early defence against invading
      microorganisms. This function is facilitated by the expression of Toll-like
      receptor (TLR) family members by neutrophils, allowing the recognition of an
      extensive repertoire of pathogen-associated molecular patterns (PAMPs) and thus
      triggering the response to invading pathogens. TLR activation leads to important
      cellular processes including reactive oxygen species (ROS) generation, cytokine
      production and increased survival, all of which can contribute to the
      pathogenesis of chronic inflammation when signalling becomes dysregulated. In
      turn, inflammation and tissue injury results in the release of endogenous TLR
      ligands, known as damage-associated molecular patterns (DAMPs), which are a
      rapidly growing class of potent inflammatory stimuli. DAMPs act in an autocrine
      manner, alerting the host of damage, but can also amplify inflammation leading to
      further tissue damage. This review highlights recent literature on neutrophil TLR
      function and regulation during disease, and provides an overview of the recently
      emerging area of neutrophil responses to DAMPs.

PMID- 21741311
TI  - Enterocyte death and intestinal barrier maintenance in homeostasis and disease.
AB  - The intestinal epithelium is the largest surface area of the body in contact with
      the external environment. This specialized single cell layer is constantly
      renewed and is a physical barrier that separates intestinal microbiota from
      underlying tissues, preventing bacterial infiltration and subsequent
      inflammation. Specialized secretory epithelial cell types such as Paneth cells
      and goblet cells limit bacterial adhesion and infiltration by secreting
      antibacterial peptides and mucins, respectively. Rapid cell renewal coincides
      with apical exfoliation of 'old' enterocytes without compromising epithelial
      barrier integrity. When the intestinal epithelium is inflamed barrier integrity
      can be compromised, due to uncontrolled death of enterocytes allowing bacterial
      infiltration. This review discusses the different mechanisms which regulate or
      affect intestinal barrier integrity under homeostatic and inflammatory
      conditions.

PMID- 21741312
TI  - Protein translation in Plasmodium parasites.
AB  - The protein translation machinery of the parasite Plasmodium is the target of
      important anti-malarial drugs, and encompasses many promising targets for future
      drugs. Plasmodium parasites have three subcellular compartments that house
      genomes; the nucleus, mitochondrion and apicoplast, and each requires its own
      compartmentalized transcription and translation apparatus for survival. Despite
      the availability of the complete genome sequence that should reveal the requisite
      elements for all three compartments, our understanding of the translation
      machineries is patchy. We review what is known about cytosolic and organellar
      translation in Plasmodium and discuss the molecules that have been identified
      through genome sequencing and post-genomic analysis. Some translation components
      are yet to be found in Plasmodium, whereas others appear to be shared between
      translationally active organelles.

PMID- 21741313
TI  - Publish or perish: a maxim relevant to authors, readers and editors alike.

PMID- 21741314
TI  - Routine use of DNA testing for red cell antigens in blood centres.
AB  - During the last decade a number of blood establishments started using molecular
      methods for typing a subset of their blood donors for minor red cell antigens as
      a part of their routine work. It can be expected that this development will
      continue and that DNA testing will take a significant role in future. A
      sufficient number of antigen-typing in the donor-database allows for the
      efficient supply of red cell units for patients who carry irregular antibodies
      directed to red cell antigens. Therefore blood centres often operate antigen
      typing programs for a subset of their repeat donors. Large-scale donor typing
      programs are labour-intensive and costly. DNA testing is a feasible alternative
      to standard serological assays. The most important advantage is the easy access
      to a spectrum of hundreds of antigens independent of the availability of
      serological reagents. Besides, that there are both positive, but also less
      favourable aspects, which are related to the different particular methods and
      platforms available for molecular testing. Several of them enable medium- and
      high-throughput applications and some are more cost-efficient than serology.

PMID- 21741315
TI  - Genetics of intracerebral haemorrhage: a tsunami effect of APOE epsilon2 genotype
      on brain bleeding size?

PMID- 21741317
TI  - The feasibility of nurse-led assessment in acute chest pain admissions by means
      of coronary computed tomography.
AB  - BACKGROUND: Cardiac computed tomography (CCT) is a non-invasive imaging technique
      for the diagnosis of coronary artery disease (CAD). The National Institute for
      Health and Clinical Excellence (NICE) recommend CCT for selected patients in the
      assessment of chest pain of recent onset. AIMS: To assess the feasibility and
      utility of CCT in a nurse-led, protocol-based assessment of chest pain. METHODS:
      Patients admitted over 4 months with suspected angina were assessed for
      eligibility for CCT by a specialist nurse. Eligibility was defined by: a
      likelihood of CAD < 90%, no features of acute coronary syndrome, no contra
      indications to the scanning process, and the ability to give written consent. An
      age and sex-matched historical cohort (for whom CCT was unavailable) was compared
      with the CCT cohort with regard to the diagnosis or exclusion of CAD at 3 months
      post-discharge from hospital. RESULTS: Of 198 patients admitted, 98 were
      identified as eligible for CCT. Of these, 37 were recommended for alternative
      management on cardiologist review, 18 declined consent, 23 were unable to be
      scanned within 24 h prior to discharge and 14 underwent CCT. CAD was diagnosed or
      excluded in 14/14 patients undergoing CCT. CAD was diagnosed or excluded in 11/14
      patients investigated without CCT, leaving 3/14 patients with no clear diagnosis.
      CONCLUSION: This study suggests nurses may be trained to assess patients for CCT
      within agreed protocols. In the UK it is likely these protocols will be based on
      NICE guidance. Despite potential diagnostic utility, CCT appears likely to form a
      small percentage of cardiac investigations undertaken.

PMID- 21741316
TI  - APOE genotype and extent of bleeding and outcome in lobar intracerebral
      haemorrhage: a genetic association study.
AB  - BACKGROUND: Carriers of APOE epsilon2 and epsilon4 have an increased risk of
      intracerebral haemorrhage (ICH) in lobar regions, presumably because of the
      effects of these gene variants on risk of cerebral amyloid angiopathy. We aimed
      to assess whether these variants also associate with severity of ICH, in terms of
      haematoma volume at presentation and subsequent outcome. METHODS: We investigated
      the association of APOE epsilon2 and epsilon4 with ICH volume and outcomes in
      patients with primary ICH in three phases: a discovery phase of 865 individuals
      of European ancestry from the Genetics of Cerebral Hemorrhage on Anticoagulation
      study, and replication phases of 946 Europeans (replication 1) and 214 African
      Americans (replication 2) from an additional six studies. We also assessed the
      association of APOE variants with ICH volume and outcomes in meta-analyses of
      results from all three phases, and the association of APOE epsilon4 with
      mortality in a further meta-analysis including data from previous reports.
      Admission ICH volume was quantified on CT scan. We assessed functional outcome
      (modified Rankin scale score 3-6) and mortality at 90 days. We used linear
      regression to establish the effect of genotype on haematoma volume and logistic
      regression to assess the effect on outcome from ICH. FINDINGS: For patients with
      lobar ICH, carriers of the APOE epsilon2 allele had larger ICH volumes than did
      non-carriers in the discovery phase (p=2.5*10(-5)), in both replication phases
      (p=0.008 in Europeans and p=0.016 in African-Americans), and in the meta-analysis
      (p=3.2*10(-8)). In the meta-analysis, each copy of APOE epsilon2 increased
      haematoma size by a mean of 5.3 mL (95% CI 4.7-5.9; p=0.004). Carriers of APOE
      epsilon2 had increased mortality (odds ratio [OR] 1.50, 95% CI 1.23-1.82;
      p=2.45*10(-5)) and poorer functional outcomes (modified Rankin scale score 3-6;
      1.52, 1.25-1.85; p=1.74*10(-5)) compared with non-carriers after lobar ICH. APOE
      epsilon4 was not associated with lobar ICH volume, functional outcome, or
      mortality in the discovery phase, replication phases, or meta-analysis of these
      three phases; in our further meta-analysis of 2194 patients, this variant did not
      increase risk of mortality (1.08, 0.86-1.36; p=0.52). APOE allele variants were
      not associated with deep ICH volume, functional outcome, or mortality.
      INTERPRETATION: Vasculopathic changes associated with the APOE epsilon2 allele
      might have a role in the severity and clinical course of lobar ICH. Screening of
      patients who have ICH to identify the epsilon2 variant might allow identification
      of those at increased risk of mortality and poor functional outcomes. FUNDING: US
      National Institutes of Health-National Institute of Neurological Disorders and
      Stroke, Keane Stroke Genetics Research Fund, Edward and Maybeth Sonn Research
      Fund, and US National Center for Research Resources.

PMID- 21741318
TI  - Analysis of indications for ureteral reimplantation in 3738 children with
      vesicoureteral reflux: a single institutional cohort.
AB  - PURPOSE: No method exists for predicting which child with vesicoureteral reflux
      (VUR) will have surgery. Our goals were to analyze practice patterns at a major
      pediatric center and to identify factors predisposing children to surgery for
      specific indications. MATERIALS AND METHODS: We analyzed a cohort of 3738
      children presenting with primary VUR (1996-2005). Surgical indications included:
      1) breakthrough urinary tract infection (UTI), 2) non-resolution over 3 years, 3)
      renal scan abnormality and 4) parent/surgeon preference. Logistic regression was
      applied to a random 60% subset of children. Validation in the remaining 40% was
      done using receiver operating characteristic curve analysis and the Hosmer and
      Lemeshow goodness-of-fit test. RESULTS: Independent predictors of surgery
      included higher age at presentation, antenatal hydronephrosis (ANH), bilateral
      VUR and VUR grade. Predictors of surgery for a breakthrough UTI included female
      gender, increasing age, and bilateral and high-grade VUR. Girls were less likely
      than boys to be operated for renal scan abnormality or parent/surgeon preference.
      ANH was a predictor of surgery for decreased function and parent/surgeon
      preference. The model had fair discrimination (c-statistic = 0.68-0.76) and high
      calibration (p >= 0.24). Probabilities of surgery were calculated. CONCLUSIONS:
      Higher age at presentation, being followed for ANH, and bilateral and high-grade
      VUR are independent predictors of VUR-corrective surgery. Predictors of surgery
      vary with indication. Our methods allow comparison of urological practice
      patterns and outcomes between institutions by taking into account indications for
      surgery.

PMID- 21741319
TI  - The influence of body mass index, sex, and race on college students' optimistic
      bias for lifestyle healthfulness.
AB  - OBJECTIVE: To examine the influence of body mass index (BMI), sex, and race on
      college students' optimistic bias (OB) concerning the healthiness of their own
      lifestyles relative to the "average college student" and best friends. DESIGN:
      Cross-sectional survey. SETTING: Large university campus. PARTICIPANTS: College
      students recruited from first-year classes (1,398 female, 985 male). VARIABLES
      MEASURED: Student height, weight, sex, race, and assessments of lifestyle
      healthfulness for self, best friends, and the "average college student."
      ANALYSIS: Paired 2-way t tests compared lifestyle ratings for self and others.
      One-way analyses of variance compared differences between BMI categories. Tukey
      Honestly Significant Difference tests tested all pairwise comparisons. Analyses
      of covariance controlling for BMI scores tested sex and race differences (P <
      .05). RESULTS: College students in all BMI categories were optimistically biased
      in comparisons to the average college student. Optimistic bias differences were
      significantly smaller, however, for self and close friends. Sex and race also
      influenced the extent and nature of OB judgments. CONCLUSIONS AND IMPLICATIONS:
      Optimistic bias may limit students' willingness to adopt and maintain more
      healthful behaviors. Optimistic bias can be reduced or even eliminated if close
      friends are specified as comparative targets. Health education campaigns,
      particularly those using socially normative approaches, should consider the
      impact of comparative target, sex, and race on OB.

PMID- 21741320
TI  - Autoantibodies to villin occur frequently in IPEX, a severe immune dysregulation,
      syndrome caused by mutation of FOXP3.
AB  - Intractable diarrhea is a major symptom of immune dysregulation,
      polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome and associated with
      autoantibodies against enterocytes. Although autoimmune enteropathy (AIE)-related
      75 kDa antigen (AIE-75) is a prominent autoantigen involved in the enteropathy
      associated with IPEX syndrome, some patients with this syndrome demonstrated
      autoantibody recognizing a 95 kDa protein rather than AIE-75 in the small
      intestine. We, herewith, identified villin, an actin-binding protein, as the 95
      kDa antigen. Four of five sera from patients with IPEX syndrome reacted with a
      fusion protein of glutathione-S-transferase and full length villin (GST-villin),
      whereas only three of 98 control sera weakly reacted with GST-villin. Anti-AIE-75
      antibody was detected in all five IPEX sera but not in normal or control disease
      sera. We conclude that both AIE-75 and villin appear to be brush border
      autoantigens in IPEX syndrome and could be used for the diagnosis of AIE in
      patients with presumptive IPEX syndrome.

PMID- 21741321
TI  - Impaired hand size estimation in CRPS.
AB  - A triad of clinical symptoms, ie, autonomic, motor and sensory dysfunctions,
      characterizes complex regional pain syndromes (CRPS). Sensory dysfunction
      comprises sensory loss or spontaneous and stimulus-evoked pain. Furthermore, a
      disturbance in the body schema may occur. In the present study, patients with
      CRPS of the upper extremity and healthy controls estimated their hand sizes on
      the basis of expanded or compressed schematic drawings of hands. In patients with
      CRPS we found an impairment in accurate hand size estimation; patients estimated
      their own CRPS-affected hand to be larger than it actually was when measured
      objectively. Moreover, overestimation correlated significantly with disease
      duration, neglect score, and increase of two-point-discrimination-thresholds
      (TPDT) compared to the unaffected hand and to control subjects' estimations. In
      line with previous functional imaging studies in CRPS patients demonstrating
      changes in central somatotopic maps, we suggest an involvement of the central
      nervous system in this disruption of the body schema. Potential cortical areas
      may be the primary somatosensory and posterior parietal cortices, which have been
      proposed to play a critical role in integrating visuospatial information.
      PERSPECTIVE: CRPS patients perceive their affected hand to be bigger than it is.
      The magnitude of this overestimation correlates with disease duration, decreased
      tactile thresholds, and neglect-score. Suggesting a disrupted body schema as the
      source of this impairment, our findings corroborate the current assumption of a
      CNS involvement in CRPS.

PMID- 21741322
TI  - Gastric bypass: a family affair--41 families in which multiple members underwent
      bariatric surgery.
AB  - BACKGROUND: The effects of multiple family members undergoing Roux-en-Y gastric
      bypass (RYGB) are unknown. The objective of our study was to evaluate RYGB in
      multiple-patient families compared with case-matched controls. METHODS: A total
      of 91 RYGB patients (family group) from 41 families with >= 2 bariatric surgeries
      were compared with 91 other RYGB patients (controls), case-matched by gender, age
      (+/- 5 yr), and body mass index (+/- 5 kg/m(2)). RESULTS: Of the 91 patients in
      the family group, 16 (18%) were men and 75 (82%) were women. The family groups
      included siblings (n = 20), father/adult offspring (n = 2), mother/adult
      offspring (n = 17), aunt or uncle/niece or nephew (n = 7), spouses (n = 12),
      cousins (n = 2), grandmother/granddaughter (n = 1), and in-laws (n = 3). Six
      families had 3 RYGB patients, and one family had 5. Incisional hernia occurred in
      17% of the family group and 24% of the control group. The office follow-up
      duration was 6 months for 89% and 83% and 1 year for 83.5% and 58% of the family
      and control groups, respectively (P < .01). The percentage of excess weight lost
      (%EWL) was 58% +/- 18% and 49% +/- 15% at 6 months and 76% +/- 18% and 62% +/-
      19% at 1 year in the family and control groups, respectively (P < .001). The %EWL
      was >80% in 45% of the family group versus in 19% of the controls (P < .01). The
      body mass index at 1 year was 31 +/- 7 kg/m(2) in the family group and 35 +/- 8
      kg/m(2) in the controls (P < .05). Among the family group siblings, the 1-year
      %EWL was 81% +/- 18% versus 60% +/- 17% in the matched control patients (P <
      .0001). CONCLUSION: The post-RYGB weight loss and follow-up were increased among
      the family patients versus the case-matched control patients. The %EWL was
      greatest among the family siblings. The results linked family ties and follow-up
      compliance with the %EWL.

PMID- 21741323
TI  - Use of the Venture catheter to shorten the door-to-balloon time in patients with
      ST-Segment elevation acute myocardial infarction.
AB  - Achieving a door-to-balloon time < 90 min may be challenging in patients with ST
      segment elevation acute myocardial infarction with difficult to wire coronary
      lesions. We report use of the Venture wire control catheter to facilitate wiring
      in four patients with significant tortuosity proximal to a thrombotic coronary
      occlusion, after conventional wiring attempts failed. Early use of the Venture
      catheter may help shorten the door-to-balloon time in patients with challenging
      to wire lesions.

PMID- 21741324
TI  - Comparison between Society of Thoracic Surgeons score and logistic EuroSCORE for
      predicting mortality in patients referred for transcatheter aortic valve
      implantation.
AB  - BACKGROUND: The primary inclusion criteria from both the Society of Thoracic
      Surgeons (STS) score and the logistic EuroSCORE are currently used to identify
      high-risk and inoperable patients eligible for transcatheter aortic valve
      implantation (TAVI). We aimed to examine the correlation between STS and logistic
      EuroSCOREs and their performance characteristics in patients referred for TAVI.
      METHODS: The study cohort consisted of 718 high-risk patients with severe aortic
      stenosis who were considered for participation in a TAVI clinical trial. The
      performance of the STS and logistic EuroSCOREs was evaluated in three groups: (a)
      medical management or balloon aortic valvuloplasty (BAV), 474 (66%); (b) 133
      patients (18.5%) with surgical aortic valve replacement (AVR); (c) 111 (15.4%)
      with TAVI. The mean age was 81.8 +/- 8.1 years, and 394 (54.8%) were female.
      RESULTS: The mean STS score was 11.5 +/- 6.1, and the mean logistic EuroSCORE was
      39.7 +/- 23.0. Pearson correlation coefficient showed moderate correlation
      between the STS and logistic EuroSCOREs (r = 0.61, P < .001). At a median follow
      up of 190 days (range, 67-476), 282 patients (39.2%) died. The STS and logistic
      EuroSCOREs were both higher in patients who died as compared to those in
      survivors (13.1 +/- 6.2 vs.10.0 +/- 5.8 and 43.4 +/- 23.1 vs. 37.5 +/- 22,
      respectively; P < .001). The observed and predicted 30-day mortality rates in the
      medical/BAV group were 10.1% observed, 12.3% by STS and 43.1% by logistic
      EuroSCORE. In the surgical AVR group, the rates were 12.8% observed, 8.4% by STS
      and 25.6% by logistic EuroSCORE. In the TAVI group, the rates were 11.7%
      observed, 11.8% by STS and 41.2% by logistic EuroSCORE. The odds ratio (OR) for
      30-day mortality in the medical/BAV group was 1.05 (P = .01) with STS and 1.003
      (P = .7) with logistic EuroSCORE. In the surgical AVR group, the OR was 1.09 (P =
      .07) with STS and 1.007 (P = .6) with logistic EuroSCORE. In the TAVI group, the
      OR was 1.14 (P = .03) with STS and 1.03 (P = .04) with logistic EuroSCORE.
      CONCLUSION: In high-risk patients with severe aortic stenosis, STS score is
      superior to the logistic EuroSCORE in predicting mortality. Clinical judgment
      should play a major role in the selection of patients with severe aortic stenosis
      for the different therapeutic options.

PMID- 21741325
TI  - Use of the CrossBoss catheter for crossing superficial femoral artery chronic
      total occlusions.
AB  - The CrossBoss chronic total occlusion catheter has been developed for the
      treatment of coronary chronic total occlusions. We report a novel use of the
      CrossBoss catheter for the crossing of a superficial femoral artery chronic total
      occlusion in three patients after conventional guidewire techniques failed.

PMID- 21741326
TI  - Percutaneous blade and balloon atrioseptostomy as a supplement to extracorporeal
      membrane oxygenation as a bridge to heart transplantation.
AB  - In patients with severe ventricular dysfunction, the extracorporeal membrane
      oxygenation (ECMO) could be insufficient to discharge the left ventricle. The
      percutaneous blade and balloon atrioseptostomy that requires transeptal catheter
      based experience could be an advisable technique to supplement assistance as a
      bridge to partial recovery or to heart transplantation. We present a case of a
      young male who presented for cardiogenic shock with a huge thrombus in the left
      main coronary artery in whom blade and balloon atrioseptostomy in addition to the
      ECMO was helpful to bail out and to perform heart transplantation.

PMID- 21741327
TI  - Anodic oxidation of oxidized forms of coenzymes Q(10) and Q(0) on carbon
      electrodes in acetic acid solutions.
AB  - The anodic oxidation of oxidized forms of coenzyme Q(10) (ubiquinone, CoQ(10))
      and Q(0) (CoQ(0)) on a glassy carbon macroelectrode (GC) and on a carbon fiber
      microelectrode (CF) was investigated in acetic acid using voltammetric
      techniques. Voltammograms recorded on these electrodes show well-defined peaks or
      waves in the potential range of above 1.5 V (vs. Ag/AgCl). The existence of these
      signals cannot be connected with the well-known redox couple CoQ/CoQH(2) but may
      be attributed to the irreversible and diffusion-controlled two-electron oxidation
      of methoxy groups in molecules of coenzymes. The overall number of electrons
      involved in the anodic oxidation of CoQ(10) is higher than for CoQ(0). This
      indicates that oxidation also proceeds in an unsaturated isoprene side chain.
      Smaller oxidation potentials for CoQ(10) in comparison to such unsaturated fatty
      acids as oleic, linoleic and linolenic ones indicate that this compound can show
      direct antioxidative properties. The antioxidative power of CoQ(10) is much
      smaller than that of reduced CoQ(10) (ubiquinol) and alpha-tocopherol. The
      results presented can be useful in the determination of this compound in real
      samples and in the assessment of biochemical properties of CoQ(10) in living
      cells.

PMID- 21741329
TI  - Computational investigation of the substrate recognition mechanism of protein D
      aspartyl (L-isoaspartyl) O-methyltransferase by docking and molecular dynamics
      simulation studies and application to interpret size exclusion chromatography
      data.
AB  - Unusual amino acid residues such as L-beta-aspartyl (Asp), D-alpha-Asp, and D
      beta-Asp have been detected in proteins and peptides such as alpha-crystallin in
      the lens and beta-amyloid in the brain. These residues increase with age, and
      hence they are associated with age-related diseases. The enzyme protein D
      aspartyl (L-isoaspartyl) O-methyltransferase (PIMT) can revert these residues
      back to the normal L-alpha-Asp residue. PIMT catalyzes transmethylation of S
      adenosylmethionine to L-beta-Asp and D-alpha-Asp residues in proteins and
      peptides. In this work, the substrate recognition mechanism of PIMT was
      investigated using docking and molecular dynamics simulation studies. It was
      shown that the hydrogen bonds of Ser60 and Val214 to the carboxyl group of Asp
      are important components during substrate recognition by PIMT. In addition,
      specific hydrogen bonds were observed between the main chains of the substrates
      and those of Ala61 and Ile212 of PIMT when PIMT recognized L-beta-Asp.
      Hydrophobic interactions between the (n-1) residue of the substrates and Ile212
      and Val214 of PIMT may also have an important effect on substrate binding. Volume
      changes upon substrate binding were also evaluated in the context of possible
      application to interpretation of size exclusion chromatography data.

PMID- 21741328
TI  - Probing for DNA damage with beta-hairpins: similarities in incision efficiencies
      of bulky DNA adducts by prokaryotic and human nucleotide excision repair systems
      in vitro.
AB  - Nucleotide excision repair (NER) is an important prokaryotic and eukaryotic
      defense mechanism that removes a large variety of structurally distinct lesions
      in cellular DNA. While the proteins involved are completely different, the mode
      of action of these two repair systems is similar, involving a cut-and-patch
      mechanism in which an oligonucleotide sequence containing the lesion is excised.
      The prokaryotic and eukaryotic NER damage-recognition factors have common
      structural features of beta-hairpin intrusion between the two DNA strands at the
      site of the lesion. In the present study, we explored the hypothesis that this
      common beta-hairpin intrusion motif is mirrored in parallel NER incision
      efficiencies in the two systems. We have utilized human HeLa cell extracts and
      the prokaryotic UvrABC proteins to determine their relative NER incision
      efficiencies. We report here comparisons of relative NER efficiencies with a set
      of stereoisomeric DNA lesions derived from metabolites of benzo[a]pyrene and
      equine estrogens in different sequence contexts, utilizing 21 samples. We found a
      general qualitative trend toward similar relative NER incision efficiencies for
      ~65% of these substrates; the other cases deviate mostly by ~30% or less from a
      perfect correlation, although several more distant outliers are also evident.
      This resemblance is consistent with the hypothesis that lesion recognition
      through beta-hairpin insertion, a common feature of the two systems, is
      facilitated by local thermodynamic destabilization induced by the lesions in both
      cases. In the case of the UvrABC system, varying the nature of the UvrC
      endonuclease, while maintaining the same UvrA/B proteins, can markedly affect the
      relative incision efficiencies. These observations suggest that, in addition to
      recognition involving the initial modified duplexes, downstream events involving
      UvrC can also play a role in distinguishing and processing different lesions in
      prokaryotic NER.

PMID- 21741330
TI  - Tetanus toxoid purification: chromatographic procedures as an alternative to
      ammonium-sulphate precipitation.
AB  - Given an existing demand to establish a process of tetanus vaccine production in
      a way that allows its complete validation and standardization, this paper focuses
      on tetanus toxoid purification step. More precisely, we were looking at a
      possibility to replace the widely used ammonium-sulphate precipitation by a
      chromatographic method. Based on the tetanus toxin's biochemical characteristics,
      we have decided to examine the possibility of tetanus toxoid purification by
      hydrophobic chromatography, and by chromatographic techniques based on
      interaction with immobilized metal ions, i.e. chelating chromatography and
      immobilized metal affinity chromatography. We used samples obtained from
      differently fragmented crude tetanus toxins by formaldehyde treatment (assigned
      as TTd-A and TTd-B) as starting material for tetanus toxoid purification.
      Obtained results imply that purification of tetanus toxoid by hydrophobic
      chromatography represents a good alternative to ammonium-sulphate precipitation.
      Tetanus toxoid preparations obtained by hydrophobic chromatography were similar
      to those obtained by ammonium-sulphate precipitation in respect to yield, purity
      and immunogenicity. In addition, their immunogenicity was similar to standard
      tetanus toxoid preparation (NIBSC, Potters Bar, UK). Furthermore, the
      characteristics of crude tetanus toxin preparations had the lowest impact on the
      final purification product when hydrophobic chromatography was the applied method
      of tetanus toxoid purification. On the other hand, purifications of tetanus
      toxoid by chelating chromatography or immobilized metal affinity chromatography
      generally resulted in a very low yield due to not satisfactory tetanus toxoid
      binding to the column, and immunogenicity of the obtained tetanus toxoid
      containing preparations was poor.

PMID- 21741331
TI  - Prevention of paracentesis-induced circulatory dysfunction in cirrhosis: standard
      vs half albumin doses. A prospective, randomized, unblinded pilot study.
AB  - BACKGROUND: Paracentesis-induced circulatory dysfunction is a well-known
      complication of large volume paracentesis. Albumin infusion (8g of albumin/L of
      ascites removed) is effective in preventing it, but high costs and scant
      availability limit its use. AIM: To compare standard vs half albumin doses.
      METHODS: Seventy cirrhotic patients treated with large volume paracentesis were
      randomized to receive intravenous albumin as prevention of paracentesis-induced
      circulatory dysfunction: group 1 (35 patients) received 4g/L of ascites removed,
      group 2 (35 patients) received 8g/L of ascites removed. RESULTS: The incidence of
      paracentesis-induced circulatory dysfunction (14% vs 20% in group 1 and group 2,
      respectively; p=ns), hyponatremia (9% vs 6%, p=ns) and renal impairment (0% in
      both groups) on the 6th day from paracentesis was similar between the two groups.
      After 6 months of follow-up, rates of survival and of recurrence of ascites
      requiring large volume paracentesis were not different between the two groups.
      CONCLUSIONS: This unblinded, randomized, pilot study suggests that treatment with
      half doses of albumin is effective in the prevention of paracentesis-induced
      circulatory dysfunction and its related clinical complications in cirrhotic
      patients with tense ascites treated by large volume paracentesis. If confirmed,
      these results could support a significant costs reduction in the management of
      ascites in cirrhotic patients.

PMID- 21741332
TI  - Pedicled rectus femoris flap for coverage of complex open pelvic fractures.
AB  - Complex open pelvic fractures are highly morbid injuries. Distant soft tissue
      transfer is often necessary for reconstruction. We report two cases of traumatic
      open pelvic fractures in which a pedicled rectus femoris flap was used for soft
      tissue coverage. Two patients presented with complex open pelvic fractures
      resulting from blunt trauma. In both patients a pedicled rectus femoris flap was
      used to reconstruct the full thickness soft tissue defect. Both patients had
      complete soft tissue coverage of the anterior pelvic defect allowing definitive
      pelvic fracture fixation. No significant donor site morbidity was associated with
      either patient post operatively. The well described pedicled rectus femoris
      flap's reliable anatomy, ease of harvest, and versatility as well as acceptable
      donor site morbidity makes this flap ideal for the reconstruction of complex open
      anterior pelvic fractures with full thickness soft tissue defects when other
      local flaps or free tissue transfer is not an option.

PMID- 21741333
TI  - Alcohol sclerodhesis: an innovative treatment for chronic Morel-Lavallee lesions.

PMID- 21741334
TI  - Aplasia cutis congenita: impact of early treatment on calvarial osteogenesis.
AB  - We describe an infant with severe aplasia cutis congenita of the scalp that was
      characterised by a full-thickness calvarial bone defect combined with the absence
      of dura mater complicated by sagittal sinus haemorrhage. The defect was
      successfully managed by closure with a local temporal flap combined with a
      periosteum patch to allow closure of the dura mater. Previously, conservative
      treatments failed to remedy unexpected, massive bleeding, which could potentially
      threaten a patient's life. We highlight the osteogenic potential of surgically
      manipulated dura mater in this patient who was managed early with a surgical
      approach.

PMID- 21741335
TI  - Accuracy in skin lesion diagnosis and the exclusion of malignancy.
AB  - The accuracy of clinical diagnosis of skin lesions has important ramifications
      for treatment selection and importantly prioritisation for treatment. The
      objective of this study was to assess the accuracy of diagnosis of skin lesions
      within our department with an emphasis placed on whether there were any negative
      consequences of a missed malignant diagnosis. The study was conducted
      retrospectively. Accuracy of diagnosis was judged on 2 criteria. The first, if
      the clinical diagnosis matched the histological diagnosis. The second, if the
      malignancy was diagnosed correctly. 1186 lesions were excised. 57% of patients
      were female and the mean age was 56 (range 6-94). 25% were invasive malignancies.
      Clinical diagnosis was correct in 700 (66%) cases. 89% BCCs and 33% of SCCs
      excised were correctly diagnosed preoperatively. Misdiagnosis of BCCs or SCCs as
      benign was associated with a stastically significant delay in treatment (BCC 6.2
      vs 10.7 weeks, p=0.02) (SCC 3.7 vs 9.5 weeks p=0.004). 100% of correctly
      diagnosed vs 79% of misdiagnosed SCCs were completely excised. The sensitivity
      and specificity of the diagnosis of MM were 87% and 97.7% respectively. The mean
      waiting time for patients correctly diagnosed preoperatively was 2.4 weeks vs 3
      weeks (p=0.39). For malignant diagnoses sensitivity was 91%, specificity 84%, PPV
      65% and NPV 96%. Misdiagnosis of skin lesions results in delays in treatment and
      may increase the rate of incomplete excision. The high NPV rate suggests that few
      malignancies are missed but those that are may have serious consequences if
      discharged untreated.

PMID- 21741336
TI  - Dorsally extended digital island flap for repairing soft tissue injury of the
      fingertip.
AB  - BACKGROUND: The digital triangular island flap is one of the most useful types of
      flap for repairing soft-tissue loss at the fingertip, because it is sensate and
      has glabrous skin. However, this type of flap has several disadvantages,
      including limited length of advancement and limited flap size. METHODS: We have
      developed a new type of dorsally extended digital island flap to extend the reach
      of the digital triangular island flap. This dorsally extended portion, 15 mm in
      width and 20 mm in length, is based on the dorsal branch of the digital artery at
      the distal phalanx level. This island flap has a longer reach than the
      conventional digital island flap and can transfer larger amounts of soft tissue
      to the injured fingertip. Sixteen patients with fingertip amputation were treated
      using this flap. RESULTS: All of the flaps survived. The dorsally extended
      digital island flap could repair pulp tissue losses up to 30 mm in length in
      oblique volar injury. In transverse injury, a new fingertip could be produced
      with this flap in a single stage. We successfully covered the exposed bone
      without shortening the digital bone of the fingertip using our extended flap. No
      claw nail deformity occurred and no flexion contracture remained in any of the
      cases. CONCLUSION: Use of a dorsally extended digital island flap is recommended
      for repairing fingertip injury in cases with defect sizes ranging from 10 to 30
      mm in length and also in both oblique volar and transverse injuries. This flap is
      more versatile for repair of fingertip injury than the conventional digital
      island flap.

PMID- 21741337
TI  - [Clinical and biological forms of secondary hyperparathyroidism in dialysis
      patients].
AB  - The diagnosis and treatment of hyperparathyroidism (HPT) are not yet well
      standardized in chronic renal failure patients. The aim of this study was to
      identify the main types of HPT on the basis of clinical and biological findings
      in a haemodialysis population. Between 2004 and 2010, all patients undergoing
      haemodialysis were observed and treated using the same strategy: conventional
      therapy with vitamin D supplements, phosphate binders, dialysate calcium adjusted
      to serum parathyroid hormone (PTH) level and calcitriol analogues (CA), along
      with regular bone marker analysis. Wherever required, cinacalcet (CC) was
      administered and parathyroidectomy (PTX) was performed. Of the 520 patients, 158
      were classified as having HPT (30%) with a serum PTH level greater than 300
      pg/mL. From this population, we identified five main types of HPT: (1) HPT with
      'no bone impact' had normal or low bone marker levels (n=28, 17.7%); (2)
      'secondary' HPT had elevated bone marker levels, but showed favorable response to
      CT (n=59, 37.7%); (3) 'tertiary' HPT was accompanied with hypercalcemia and
      required CC or PTX in case of CT failure (n=11, 6.9%); (4) 'mixed' HPT could not
      be completely treated with CT and required CC or PTX (n=57, 36%); (5) 'resistant'
      HPT did not show hypercalcemia, but required PTX after CT and CC failure (n=3,
      1.8%). CC was prescribed in 51% cases, CA in 76%, and PTX in 7% of cases. We
      typified HPT on the basis of physiopathology and stages of HPT progression.
      Further studies on HPT that focus on bone marker levels are required to establish
      well-defined treatment strategies. In our study, HPT cases did not show uniform
      findings in Hemodialyse (HD) patients because of the variation in the stages of
      the disease at the time of diagnosis.

PMID- 21741338
TI  - Egg forensics: an appraisal of DNA sequencing to assist in species identification
      of illegally smuggled eggs.
AB  - Psittaciformes (parrots and cockatoos) are charismatic birds, their plumage and
      capacity for learning make them highly sought after pets. The illegal trade in
      parrots and cockatoos poses a serious threat to the viability of native
      populations; in addition, species transported to non-endemic areas may
      potentially vector disease and genetically 'pollute' local native avifauna. To
      reduce the logistical difficulties associated with trafficking live birds,
      smugglers often transport eggs. This creates a problem for authorities in
      elucidating accurate species identification without the laborious task of
      incubation and hand rearing until a morphological identification can be made.
      Here, we use 99 avian eggs seized from carriers coming into and within Australia,
      as a result of suspected illegal trade. We investigate and evaluate the use of
      mitochondrial DNA (mtDNA) to accurately identify eggs to family, genus or species
      level. However, Identification of a species based on percentage mtDNA
      similarities is difficult without good representations of the inter- and intra
      levels of species variation. Based on the available reference database, we were
      able to identify 52% of the eggs to species level. Of those, 10 species from
      eight genera were detected, all of which belong to the parrot (Psittacidae) and
      cockatoo (Cacatuidae) families. Of the remaining 48%, a further 36% of eggs were
      identified to genus level, and 12% identified to family level using our
      assignment criteria. Clearly the lack of validated DNA reference sequences is
      hindering our ability to accurately assign a species identity, and accordingly,
      we advocate that more attention needs to be paid to establishing validated, multi
      locus mtDNA reference databases for exotic birds that can both assist in genetic
      identifications and withstand legal scrutiny.

PMID- 21741339
TI  - Salivary histatin-5, a physiologically relevant ligand for Ni(II) ions.
AB  - Histatins are a family of human salivary antimicrobial peptides. Histatin-5 (Hst
      5, DSHAKRHHGYKRKFHEKHHSHRGY), a prominent member of this family contains an
      albumin-like, N-terminal Asp-Ser-His sequence, known to bind a Ni(II) ion in a
      square-planar geometry. Nickel is a strong allergen, and oral exposure to Ni(II)
      ions can elicit allergic reaction in sensitized persons. In contrast, prior oral
      exposure to nickel in non-sensitized persons can prevent sensitization. The fate
      of Ni(II) ions in saliva is obviously important for these processes, yet little
      is known about it. Using potentiometry, UV-visible titrations and circular
      dichroism, we determined stability constants for Ni(II) complexes of Hst-5 and
      two truncated analogs, 5Hst-5 (DSHAK) and 10Hst-5 (DSHAKRHHGY). The conditional
      binding constant at pH 7.4 for Hst-5 was 10(7.5+/-0.2), compared to the
      corresponding value for albumin, 10(6.8+/-0.3) (M. Sokolowska, A. Krezel, M.
      Dyba, Z. Szewczuk, W. Bal, Eur. J. Biochem. 269 (2002) 1323-1331). These values
      indicate that Hst-5 binds Ni(II) five times stronger than HSA. The simulated
      competition for Ni(II) between Hst-5 and albumin shows that significant amounts
      of Ni(II) ions may be carried by Hst-5 in vivo. Therefore, Hst-5 and other
      histatins should be considered as factors in nickel allergy and other forms of
      nickel toxicity.

PMID- 21741340
TI  - The role of working memory in compulsive checking and OCD: a systematic
      classification of 58 experimental findings.
AB  - Despite the large body of research regarding the role of memory in OCD, the
      results are described as mixed at best (Hermans et al., 2008). For example,
      inconsistent findings have been reported with respect to basic capacity, intact
      verbal, and generally affected visuospatial memory. We suggest that this is due
      to the traditional pursuit of OCD memory impairment as one of the general
      capacity and/or domain specificity (visuospatial vs. verbal). In contrast, we
      conclude from our experiments (i.e., Harkin & Kessler, 2009, 2011; Harkin,
      Rutherford, & Kessler, 2011) and recent literature (e.g., Greisberg & McKay,
      2003) that OCD memory impairment is secondary to executive dysfunction, and more
      specifically we identify three common factors (EBL: Executive-functioning
      efficiency, Binding complexity, and memory Load) that we generalize to 58
      experimental findings from 46 OCD memory studies. As a result we explain
      otherwise inconsistent research - e.g., intact vs. deficient verbal memory - that
      are difficult to reconcile within a capacity or domain specific perspective. We
      conclude by discussing the relationship between our account and others', which in
      most cases is complementary rather than contradictory.

PMID- 21741341
TI  - Limits in detecting an individual dopant atom embedded in a crystal.
AB  - Annular dark field scanning transmission electron microscope (ADF-STEM) images
      allow detection of individual dopant atoms located on the surface of or inside a
      crystal. Contrast between intensities of an atomic column containing a dopant
      atom and a pure atomic column in ADF-STEM image depends strongly on specimen
      parameters and microscope conditions. Analysis of multislice-based simulations of
      ADF-STEM images of crystals doped with one substitutional dopant atom for a wide
      range of crystal thicknesses, types and locations of dopant atom inside the
      crystal, and crystals with different atoms reveal some interesting trends and non
      intuitive behaviours in visibility of the dopant atom. The results provide
      practical guidelines to determine the optimal microscope and specimen conditions
      to detect a dopant atom in experiment, obtain information about the 3-d location
      of a dopant atom, and recognize cases where detecting a single dopant atom is not
      possible.

PMID- 21741342
TI  - Extended ptychography in the transmission electron microscope: possibilities and
      limitations.
AB  - The extended-ptychographical iterative engine (e-PIE) is a recently developed
      powerful phase retrieval algorithm which can be used to measure the phase
      transfer function of a specimen and overcome conventional lens resolution limits.
      The major improvement over PIE is the ability to reconstruct simultaneously both
      the object and illumination functions, robustness to noise and speed of
      convergence. The technique has proven to be successful at optical and X-ray
      wavelengths and we describe here experimental results in transmission electron
      microscopy supported by corresponding simulations. These simulations show the
      possibilities - even with strong phase objects - and limitations of ptychography;
      in particular issues arising from poorly-defined probe positions.

PMID- 21741343
TI  - Prospects for lithium imaging using annular bright field scanning transmission
      electron microscopy: a theoretical study.
AB  - There is strong interest in lithium imaging, particularly because of its
      significance in battery materials. However, light atoms only scatter electrons
      weakly and atomic resolution direct imaging of lithium has proven difficult. This
      paper explores theoretically the conditions under which lithium columns can be
      expected to be directly visible using annular bright field scanning transmission
      electron microscopy. A detailed discussion is given of the controllable
      parameters and the conditions most favourable for lithium imaging.

PMID- 21741344
TI  - Improvement in liver pathology of patients with beta-thalassemia treated with
      deferasirox for at least 3 years.
AB  - BACKGROUND & AIMS: Most data on the effects of iron chelation therapy for
      patients with liver fibrosis come from small studies. We studied the effects of
      the oral iron chelator deferasirox on liver fibrosis and necroinflammation in a
      large population of patients with iron overload beta-thalassemia. METHODS: We
      studied data from 219 patients with beta-thalassemia, collected from histologic
      analyses of biopsy samples taken at baseline and after at least 3 years of
      treatment with deferasirox. Treatment response was assessed from liver iron
      concentrations at baseline and the end of the study. Liver fibrosis,
      necroinflammation, and markers of iron overload and liver enzymes were recorded.
      Patients were also assessed, by serologic analysis at baseline, for hepatitis C
      virus infection. RESULTS: By the end of the study, stability of Ishak fibrosis
      staging scores (change of -1, 0, or +1) or improvements (change of <=-2) were
      observed in 82.6% of patients; Ishak necroinflammatory scores improved by a mean
      value of -1.3 (P<.001). Improvements in fibrosis stage and necroinflammation were
      independent of hepatitis C virus exposure or reduction in liver iron
      concentration defined by the response criteria. Absolute changes in
      concentrations of liver iron by the end of the study did not correlate with
      improved Ishak fibrosis or necroinflammatory scores. CONCLUSIONS: Deferasirox
      treatment for 3 or more years reversed or stabilized liver fibrosis in 83% of
      patients with iron-overloaded beta-thalassemia. This therapeutic effect was
      independent of reduced concentration of liver iron (defined by the response
      criteria) or previous exposure to hepatitis C virus.

PMID- 21741345
TI  - Can serotonin agonists unlock age-dependent failure of liver regeneration?

PMID- 21741346
TI  - A brief encounter.

PMID- 21741347
TI  - Adrenaline-Proven benefit in cardiac arrest at last?

PMID- 21741348
TI  - Seroepidemiological survey of Leishmania infantum infection in dogs from
      northeastern Portugal.
AB  - Northeastern Portugal is a region where canine leishmaniasis (CanL) is endemic.
      In this study, a sero-epidemiological survey was conducted in 654 dogs from that
      geographical area. Serum samples were evaluated by the direct agglutination test
      (DAT) and also by enzyme-linked immunosorbent assay (ELISA) using five different
      defined antigens. Seroprevalence of infection was 21.3% based on the assumption
      that seropositive animals were positive for at least three tests. A high degree
      of agreement was found between DAT and LAM-ELISA (89%; kappa value [kappa] =
      0.67). A statistically significant difference (p<0.05) of seropositivity was
      found between adult (23.4%) and juvenile dogs (12.2%), apparently healthy (14.8%)
      and sick dogs (40.2%), vaccinated (19.7%) and non-vaccinated (41.2%) animals,
      seropositive (26.9%) and seronegative (18.0%) for Toxoplasma gondii, living in
      rural (18.5%) or urban (32.6%) areas, and between animals living exclusively
      outdoors (18.2%) and those living in a mixed habitat (27.5%). Risk factors for
      canine Leishmania infection, as defined by multiple logistic regression analysis,
      were of clinical status (odds ratio [OR] = 3.1) and Toxoplasma infection (OR =
      1.5).

PMID- 21741350
TI  - Classification within the cosmopolitan genus Culex (Diptera: Culicidae): the
      foundation for molecular systematics and phylogenetic research.
AB  - The internal classification of the cosmopolitan and medically important genus
      Culex is thoroughly reviewed and updated to reflect the multitude of taxonomic
      changes and concepts which have been published since the classification was last
      compiled by Edwards in 1932. Both formal and informal taxa are included. The
      classification is intended to aid researchers and students who are interested in
      analyzing species relationships, making group comparisons and testing
      phylogenetic hypotheses. The genus includes 768 formally recognized species
      divided among 26 subgenera. Many of the subgenera are subdivided hierarchically
      into nested informal groups of morphologically similar species that are believed
      to represent monophyletic lineages based on morphological similarity. The
      informal groupings proposed by researchers include Sections, Series, Groups,
      Lines, Subgroups and Complexes, which are unlikely to be phylogenetically
      equivalent categories among the various subgenera.

PMID- 21741349
TI  - Malaria in selected non-Amazonian countries of Latin America.
AB  - Approximately 170 million inhabitants of the American continent live at risk of
      malaria transmission. Although the continent's contribution to the global malaria
      burden is small, at least 1-1.2 million malaria cases are reported annually.
      Sixty percent of the malaria cases occur in Brazil and the other 40% are
      distributed in 20 other countries of Central and South America. Plasmodium vivax
      is the predominant species (74.2%) followed by P. falciparum (25.7%) and P.
      malariae (0.1%), and no less than 10 Anopheles species have been identified as
      primary or secondary malaria vectors. Rapid deforestation and agricultural
      practices are directly related to increases in Anopheles species diversity and
      abundance, as well as in the number of malaria cases. Additionally, climate
      changes profoundly affect malaria transmission and are responsible for malaria
      epidemics in some regions of South America. Parasite drug resistance is
      increasing, but due to bio-geographic barriers there is extraordinary genetic
      differentiation of parasites with limited dispersion. Although the clinical
      spectrum ranges from uncomplicated to severe malaria cases, due to the generally
      low to middle transmission intensity, features such as severe anemia, cerebral
      malaria and other complications appear to be less frequent than in other endemic
      regions and asymptomatic infections are a common feature. Although the National
      Malaria Control Programs (NMCP) of different countries differ in their control
      activities these are all directed to reduce morbidity and mortality by using
      strategies like health promotion, vector control and impregnate bed nets among
      others. Recently, international initiatives such as the Malaria Control Program
      in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism
      for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis
      and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial
      Drug Resistance (RAVREDA) (sponsored by the Pan American Health
      Organization/World Health Organization (PAHO/WHO) and several other partners),
      have made great investments for malaria control in the region. We describe here
      the current status of malaria in a non-Amazonian region comprising several
      countries of South and Central America participating in the Centro Latino
      Americano de Investigacion en Malaria (CLAIM), an International Center of
      Excellence for Malaria Research (ICEMR) sponsored by the National Institutes of
      Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID).

PMID- 21741351
TI  - KSHV regulation of fibulin-2 in Kaposi's sarcoma: implications for tumorigenesis.
AB  - Kaposi's sarcoma is an angioproliferative tumor caused by Kaposi's sarcoma
      associated herpesvirus (KSHV) infection of vascular endothelial cells. Fibulins,
      proteins that associate with extracellular matrix (ECM) proteins, may have both
      tumor-suppressive and oncogenic activities. We found that the expression of
      fibulin-2 protein and mRNA were decreased 50-fold and 26-fold, respectively, in
      10-day KSHV-infected dermal microvascular endothelial cells (DMVEC). Using
      quantitative RT-PCR, we found a fivefold and 25-fold decrease of fibulin-2
      extracellular matrix binding partners, fibronectin and tropoelastin,
      respectively. Time-course transcriptional analyses over 10 days showed that in
      addition to that of fibulin-2, expression of fibulins 3 and 5 was decreased in
      KSHV-infected DMVEC, fibulins 1C/1D were increased, and fibulins 4, 6, and 7 were
      unchanged. KSHV latency-associated nuclear antigen (LANA) transcription levels
      rose consistently over the same period. Addition of recombinant fibulin-3 or -5
      for 48 hours to 10-day KSHV-infected cells caused a suppression of KSHV-induced
      vascular endothelial growth factor (VEGF) protein and mRNA levels. Recombinant
      fibulin-3 also significantly reduced VEGF receptor 3 expression. In pleural
      effusion lymphoma cell lines that express variable levels of KSHV lytic
      replication, we observed no detectable fibulin-2 or -5 expression. Finally,
      fibulin-2 expression was decreased in tissue microarrays from KSHV-infected, LANA
      positive patient cells as compared to that in patient nontumor controls.
      Understanding the interactions between KSHV and the fibulins may lead to the
      development of novel therapies for treatment of Kaposi's sarcoma.

PMID- 21741352
TI  - Curcumin modulates PKCalpha activity by a membrane-dependent effect.
AB  - Curcumin modulates the activity of protein kinase Calpha (PKCalpha) when assayed
      in the presence of vesicles including phosphatidylcholine, phosphatidylserine and
      diacylglycerol. Increasing concentrations of curcumin progressively increased
      PKCalpha activity at concentrations lower than 20MUM, but at higher
      concentrations of curcumin the activity decreased although, at concentrations of
      curcumin of up to 100MUM the activity was always higher than the basal one (in
      the absence of curcumin). The maximum activity was reached at 3MUM curcumin, at
      20 and 30mol% of phosphatidylserine, 10MUM Ca(2+) and 2mol% diacylglycerol. The
      same type of modulation was observed when changing the concentration of
      phosphatidylserine, diacylglycerol and Ca(2+). No effect of curcumin was found
      when the activity was assayed in the presence of Triton X-100 mixed micelles
      which included phosphatidylserine and diacylglycerol, indicating that the effect
      of curcumin was membrane-dependent. The pattern of binding of PKCalpha to
      membrane vesicles as a function of curcumin concentration closely correlated with
      the pattern of activating effect. It was concluded that the effect of curcumin on
      PKCalpha activity was related to its effect on the membrane, which may modulate
      the binding of the enzyme to the membrane.

PMID- 21741353
TI  - Mutations of human cytochrome P450 reductase differentially modulate heme
      oxygenase-1 activity and oligomerization.
AB  - Genetic variations in POR, encoding NADPH-cytochrome P450 oxidoreductase (CYPOR),
      can diminish the function of numerous cytochromes P450, and also have the
      potential to block degradation of heme by heme oxygenase-1 (HO-1). Purified full
      length human CYPOR, HO-1, and biliverdin reductase were reconstituted in lipid
      vesicles and assayed for NADPH-dependent conversion of heme to bilirubin.
      Naturally-occurring human CYPOR variants queried were: WT, A115V, Y181D, P228L,
      M263V, A287P, R457H, Y459H, and V492E. All CYPOR variants exhibited decreased
      bilirubin production relative to WT, with a lower apparent affinity of the CYPOR
      HO-1 complex than WT. Addition of FMN or FAD partially restored the activities of
      Y181D, Y459H, and V492E. When mixed with WT CYPOR, only the Y181D CYPOR variant
      inhibited heme degradation by sequestering HO-1, whereas Y459H and V492E were
      unable to inhibit HO-1 activity suggesting that CYPOR variants might have
      differential binding affinities with redox partners. Titrating the CYPOR-HO-1
      complex revealed that the optimal CYPOR:HO-1 ratio for activity was 1:2, lending
      evidence in support of productive HO-1 oligomerization, with higher ratios of
      CYPOR:HO-1 showing decreased activity. In conclusion, human POR mutations, shown
      to impact P450 activities, also result in varying degrees of diminished HO-1
      activity, which may further complicate CYPOR deficiency.

PMID- 21741354
TI  - Pulmonary surfactant proteins and polymer combinations reduce surfactant
      inhibition by serum.
AB  - Acute respiratory distress syndrome (ARDS) is an inflammatory condition that can
      be associated with capillary leak of serum into alveoli causing inactivation of
      surfactant. Resistance to inactivation is affected by types and concentrations of
      surfactant proteins, lipids, and polymers. Our aim was to investigate the effects
      of different combinations of these three components. A simple lipid mixture
      (DPPC/POPG) or a more complex lipid mixture (DPPC/POPC/POPG/cholesterol) was
      used. Native surfactant proteins SP-B and SP-C obtained from pig lung lavage were
      added either singly or combined at two concentrations. Also, non-ionic polymers
      polyethylene glycol and dextran and the anionic polymer hyaluronan were added
      either singly or in pairs with hyaluronan included. Non-ionic polymers work by
      different mechanisms than anionic polymers, thus the purpose of placing them
      together in the same surfactant mixture was to evaluate if the combination would
      show enhanced beneficial effects. The resulting surfactant mixtures were studied
      in the presence or absence of serum. A modified bubble surfactometer was used to
      evaluate surface activities. Mixtures that included both SP-B and SP-C plus
      hyaluronan and either dextran or polyethylene glycol were found to be the most
      resistant to inhibition by serum. These mixtures, as well as some with either SP
      B or SP-C with combined polymers were as or more resistant to inactivation than
      native surfactant. These results suggest that improved formulations of lung
      surfactants are possible and may be useful in reducing some types of surfactant
      inactivation in treating lung injuries.

PMID- 21741355
TI  - Effects of signal sequence on phage-displayed disulfide-stabilized single chain
      antibody variable fragment (sc-dsFv) libraries.
AB  - Phage-displayed single chain variable fragment (scFv) libraries are powerful
      tools in antibody engineering. Disulfide-stabilized scFv (sc-dsFv) with an
      interface disulfide bond is structure-wise more stable than the corresponding
      scFv. A set of recently discovered signal sequences replacing the wild type
      (pelB) signal peptidase cleavage site in the c-region has been shown to be
      effective in rescuing the expression of sc-dsFv libraries on the phage surface.
      However, the effects of the other regions of the signal sequence on the
      expression of the sc-dsFv libraries and on the formation of the interface
      disulfide bond in the phage-displayed sc-dsFv have not been clear. In this work,
      selected novel signal sequence variants in the h-region were shown to be equally
      effective in promoting sc-dsFv library expression on the phage surface; the
      expression level and complexity of the sc-dsFv libraries were comparable to the
      corresponding scFv libraries produced with the wild-type (pelB) signal sequence.
      The interface disulfide bond in the phage-displayed sc-dsFv was proven to form to
      a large extent in the library variant ensemble generated with signal sequence
      variants in both the h-region and the c-region. The sc-dsFv engineering platform
      established in this work can be applied to many of the known scFv molecules which
      are in need of a more stable version for the applications under harsh conditions
      or for longer shelf-life.

PMID- 21741356
TI  - The effect of the dilated cardiomyopathy-causing Glu40Lys TPM1 mutation on actin
      myosin interactions during the ATPase cycle.
AB  - Dilated cardiomyopathy (DCM), characterized by cardiac dilatation and contractile
      dysfunction, is a major cause of heart failure. DCM can result from mutations in
      the gene encoding cardiac alpha-tropomyosin (TM). In order to understand how the
      dilated cardiomyopathy-causing Glu40Lys mutation in TM affects actomyosin
      interactions, thin filaments have been reconstituted in muscle ghost fibers by
      incorporation of labeled Cys707 of myosin subfragment-1 and Cys374 of actin with
      fluorescent probe 1.5-IAEDANS and alpha-tropomyosin (wild-type or Glu40Lys
      mutant). For the first time, the effect of these alpha-tropomyosins on the
      mobility and rotation of subdomain-1 of actin and the SH1 helix of myosin
      subfragment-1 during the ATP hydrolysis cycle have been demonstrated directly by
      polarized fluorimetry. The Glu40Lys mutant TM inhibited these movements at the
      transition from AM(**).ADP.Pi to AM state, indicating a decrease of the
      proportion of the strong-binding sub-states in the actomyosin population. These
      structural changes are likely to underlie the contractile deficit observed in
      human dilated cardiomyopathy.

PMID- 21741357
TI  - Characterization of the in vitro expressed autoimmune rippling muscle disease
      immunogenic domain of human titin encoded by TTN exons 248-249.
AB  - Autoimmune rippling muscle disease (ARMD) is an autoimmune neuromuscular disease
      associated with myasthenia gravis (MG). Past studies in our laboratory recognized
      a very high molecular weight skeletal muscle protein antigen identified by ARMD
      patient antisera as the titin isoform. These past studies used antisera from ARMD
      and MG patients as probes to screen a human skeletal muscle cDNA library and
      several pBluescript clones revealed supporting expression of immunoreactive
      peptides. This study characterizes the products of subcloning the titin
      immunoreactive domain into pGEX-3X and the subsequent fusion protein. Sequence
      analysis of the fusion gene indicates the cloned titin domain (GenBank ID:
      EU428784) is in frame and is derived from a sequence of N2-A spanning the exons
      248-250 an area that encodes the fibronectin III domain. PCR and EcoR1
      restriction mapping studies have demonstrated that the inserted cDNA is of a size
      that is predicted by bioinformatics analysis of the subclone. Expression of the
      fusion protein result in the isolation of a polypeptide of 52 kDa consistent with
      the predicted inferred amino acid sequence. Immunoblot experiments of the fusion
      protein, using rippling muscle/myasthenia gravis antisera, demonstrate that only
      the titin domain is immunoreactive.

PMID- 21741358
TI  - Isoflurane preconditioning involves upregulation of molecular chaperone genes.
AB  - Isoflurane preconditioning is a phenomenon in which cells previously exposed to
      isoflurane exhibit protection against subsequent noxious stimuli. We hypothesize
      that isoflurane may cause subtle protein misfolding that persists at a sublethal
      level, stimulating cytoprotective mechanisms. Human neuroblastoma cells (SH-SY5Y)
      were exposed to isoflurane followed by quantitative analysis of the expression of
      several families of heat shock genes (84 total transcripts). Our data is
      consistent with a model of an early and delayed phase of preconditioning.
      Different patterns of expression of the 84 genes were seen at 1 and 24h post
      isoflurane exposure. Expression of 45 of the 84 genes were elevated at 1h (or
      early phase) and remained upregulated at 24h (or delayed phase). Subsets of the
      remaining genes were either unchanged (13 genes), early-specific upregulated (17
      genes) or delayed-specific upregulated (9 genes). We also demonstrated that
      isoflurane caused a slight yet detectable misfold of a model protein. These data
      indicate that brief anesthetic exposure promotes specific patterns of gene
      expression, leading to preconditioning which would enhance the cell's ability to
      tolerate a future injury that involves protein misfolding.

PMID- 21741359
TI  - Toward the smallest active subdomain of a TIM-barrel fold: insights from a
      truncated alpha-amylase.
AB  - AmyTM is a truncated mutant of the alpha-amylase of Bacillus stearothermophilus
      US100. It has been derived from the wild type amylase gene via a reading frame
      shift, following a tandem duplication of the mutant primer, associated to an
      Adenine base deletion. AmyTM was composed of 720 nucleotides encoding 240 amino
      acid residues out of 549 of the wild type. The AmyTM protein was devoided of the
      three catalytic residues but still retains catalytic activity. It is Ca
      independent maltotetraose producing amylase, optimally active at pH 6 and 60
      degrees C, under monomeric or multimeric forms. AmyTM is the smallest functional
      truncated TIM barrel. It contains the betaalphabetaalpha unit as the minimal
      subdomain associated to an enzymatic function. The enzymatic activity can, until
      now, be attributed to the presence of the whole domain B, in the structure of
      AmyTM. This mutant revealed, for the first time, the regeneration of a catalytic
      site after its abolition. This fact may be considered as the restoration of a
      primitive active site, which was lost in the course of evolution toward more
      stable domains.

PMID- 21741360
TI  - Secretion of N-terminal domain of alpha-dystroglycan in cerebrospinal fluid.
AB  - alpha-Dystroglycan (alpha-DG) plays crucial roles in maintaining the stability of
      cells. We demonstrated previously that the N-terminal domain of alpha-DG (alpha
      DG-N) is secreted by cultured cells into the culture medium. In the present
      study, to clarify its function in vivo, we generated a monoclonal antibody
      against alpha-DG-N and investigated the secretion of alpha-DG-N in human
      cerebrospinal fluid (CSF). Interestingly, we found that a considerable amount of
      alpha-DG-N was present in CSF. alpha-DG-N in CSF was a sialylated glycoprotein
      with both N- and O-linked glycan. These observations suggest that secreted alpha
      DG-N may be transported via CSF and have yet unidentified effects on the nervous
      system.

PMID- 21741361
TI  - Anti-inflammatory effect of transduced PEP-1-heme oxygenase-1 in Raw 264.7 cells
      and a mouse edema model.
AB  - Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to
      biliverdin, carbon monoxide (CO), and free iron (Fe(2+)), is up-regulated by
      several cellular stress and cell injuries, including inflammation, ischemia and
      hypoxia. In this study, we examined whether fusion of HO-1 with PEP-1, a protein
      transduction domain that is able to deliver exogenous molecules to living cells
      or tissues, would facilitate HO-1 delivery to target cells and tissues, and
      thereby effectively exert a therapeutically useful response against inflammation.
      Western blot analysis demonstrated that PEP-1-HO-1 fusion proteins were
      transduced into Raw 264.7 cells in time- and dose-dependent manners, and were
      stably maintained in the cells for about 60h. In addition, fluorescence analysis
      revealed that only PEP-1-HO-1 fusion proteins were significantly transduced into
      the cytoplasm of cells, while HO-1 proteins failed to be transduced. In
      lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and 12-O-tetradecanoylphorbol
      13-acetate (TPA)-induced mouse edema model, transduced PEP-1-HO-1 fusion proteins
      effectively inhibited the overexpression of pro-inflammatory mediators and
      cytokines. Also, histological analysis demonstrated that PEP-1-HO-1 remarkably
      suppressed ear edema. The results suggest that the PEP-1-HO-1 fusion protein can
      be used as a therapeutic molecule against reactive oxygen species-related
      inflammatory diseases.

PMID- 21741362
TI  - Involvement of Cot activity in the proliferation of ALCL lymphoma cells.
AB  - Anaplastic large-cell lymphoma (ALCL) cells overexpress CD30 on their cell
      surface, show increased levels of activated Erk1/2 and of JunB; participating
      JunB in the proliferative capacity of these lymphomas. Here, we show that ALCL
      lymphoma cells also present high expression levels of the proto-oncogenic Cot
      (MAP3K8). Using pharmacological drugs as well as the RNA interference technique
      we show that Cot protein is responsible for the constitutive Erk1/2 activation in
      the ALCL lymphoma cells, SUDHL-1. Besides, inhibition of Cot activity reduces the
      number of cell divisions which is achieved, at least in part, by the control that
      Cot exercises on the activation state of p70 S6K and on the expression levels of
      JunB. Since Cot represents an alternative mode, independently of RAF, to activate
      Erk1/2, all these data strongly suggest that molecular targeting of Cot may be a
      potential new specific strategy for ALCL lymphomas therapy, without the fully
      disturbance of the Erk1/2 function.

PMID- 21741363
TI  - Regulated production of the pituitary hormone oxytocin from murine and human
      osteoblasts.
AB  - Oxytocin (OT) is a primitive neurohypophyseal hormone that plays a primary and
      indispensible role in mammalian lactation. We have shown recently that OT also
      regulates bone remodeling, mainly bone formation, with remarkable sensitivity. We
      now show that OT, apart from its neurohypophyseal origin, is produced in
      abundance by both human and murine osteoblasts. Production of osteoblast OT is
      under the control of estrogen, which acts by activating the MAP kinase Erk. This
      non-genomic mechanism of estrogen action is in stark contrast to its genomic
      control of OT receptor (OTR) expression. We surmise that there is a local feed
      forward loop in bone marrow through which the OT so produced from osteoblasts in
      response to estrogen acts upon its receptor to exert a potent anabolic action.

PMID- 21741364
TI  - Neuroprotective cytokines repress PUMA induction in the 1-methyl-4
      phenylpyridinium (MPP(+)) model of Parkinson's disease.
AB  - The hematopoietic cytokines erythropoietin (Epo) and granulocyte-colony
      stimulating factor (G-CSF) provide neuroprotection in several in vitro and in
      vivo models of Parkinson's disease (PD). The molecular mechanism by which Epo and
      G-CSF signals reduce the neuronal death in PD is not clear. Here, we show that in
      rat pheochromocytoma PC12 cells, Epo and G-CSF efficiently repressed the 1-methyl
      4-phenylpyridinium (MPP(+))-induced expression of the proapoptotic protein PUMA
      (p53 up-regulated modulator of apoptosis). Accordingly, Epo and G-CSF treatment
      reduced the PC12 cell fraction that underwent apoptosis by MPP(+) treatment and
      thus improved cell viability. Downregulation of PUMA expression by Epo and G-CSF
      in MPP(+)-treated PC12 cells seems to be mediated by repression of p53, as the
      expression of p53 was increased by MPP(+)-treatment and reduced by Epo and G-CSF.
      Together, these results suggest that the neuroprotective activities of Epo and G
      CSF in an experimental model of PD involve the repression of the apoptosis
      inducing action of PUMA.

PMID- 21741365
TI  - Distinct expression patterns of the subunits of the CCR4-NOT deadenylase complex
      during neural development.
AB  - The stability of mRNA influences the dynamics of gene expression. The mammalian
      CCR4-NOT complex is associated with deadenylase activity, which shortens the mRNA
      poly(A) tail and thereby contributes to destabilization of mRNAs. The complex
      consists of at least nine subunits and predominantly forms a 2.0MDa protein
      complex in HeLa cells. Accumulating evidence suggests that the CCR4-NOT complex
      is involved in cell growth and survival; however, the regulatory mechanisms of
      its biological activity remain obscure. Here, we analyzed the expression levels
      of the subunits of the CCR4-NOT complex in various mouse tissues and found that
      they showed distinct expression patterns. CNOT6, 6L, 7, and 10 were expressed
      nearly ubiquitously, whereas others were expressed in tissue-specific manners,
      such as those displaying especially high expression in the brain. Furthermore,
      CNOT2, 3, 6, and 8 were rapidly downregulated during differentiation of neural
      stem cells. These findings suggest that subunit composition of the CCR4-NOT
      complex differs among tissues and is altered during neural development, thereby
      imparting an additional layer of specificity in the control of gene expression.

PMID- 21741366
TI  - Pioglitazone promotes preadipocyte proliferation by downregulating p16(Ink4a).
AB  - Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor
      (PPAR)gamma, causes preadipocyte proliferation through a mechanism which still
      remains elusive. Here, to address the mechanism, we investigated the effects of
      PPARgamma and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors,
      especially with p16(Ink4a) (p16) centered, by employing 3T3-L1 preadipocytes.
      Pioglitazone promoted preadipocyte proliferation by increasing S and G(2)/M cell
      cycle entry, which was accompanied by decreased p16 mRNA expression. PPARgamma
      overexpression along with the luciferase reporter assay confirmed that PPARgamma
      was crucial for the downregulation of p16 mRNA transcription, and that the action
      was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent
      promoting effect on preadipocyte proliferation, of which mechanisms include p16
      downregulation through PPARgamma.

PMID- 21741367
TI  - Piperidine alkaloids from Piper retrofractum Vahl. protect against high-fat diet
      induced obesity by regulating lipid metabolism and activating AMP-activated
      protein kinase.
AB  - The fruits of Piper retrofractum Vahl. have been used for their anti-flatulent,
      expectorant, antitussive, antifungal, and appetizing properties in traditional
      medicine, and they are reported to possess gastroprotective and cholesterol
      lowering properties. However, their anti-obesity activity remains unexplored. The
      present study was conducted to isolate the anti-obesity constituents from P.
      retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced
      obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including
      piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti
      obesity constituents through a peroxisome proliferator-activated receptor delta
      (PPARdelta) transactivation assay. The molecular mechanism was investigated in
      3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein
      kinase (AMPK) signaling and PPARdelta protein and also regulated the expression
      of lipid metabolism-related proteins. In the animal model, oral PRPA
      administration (50, 100, or 300mg/kg/day for 8weeks) significantly reduced HFD
      induced body weight gain without altering the amount of food intake. Fat pad mass
      was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size.
      In addition, elevated serum levels of total cholesterol, low-density lipoprotein
      cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment.
      PRPA also protected against the development of nonalcoholic fatty liver by
      decreasing hepatic triglyceride accumulation. Consistent with the in vitro
      results, PRPA activated AMPK signaling and altered the expression of lipid
      metabolism-related proteins in liver and skeletal muscle. Taken together, these
      findings demonstrate that PRPAs attenuate HFD-induced obesity by activating AMPK
      and PPARdelta, and regulate lipid metabolism, suggesting their potential anti
      obesity effects.

PMID- 21741368
TI  - Mitochondrial myopathy in a child with a muscle-restricted mutation in the
      mitochondrial transfer RNAAsn gene.
AB  - We report an 11-year-old boy with exercise-related myopathy, and a novel mutation
      m.5669G>A in the mitochondrial tRNA Asparagine gene (mt-tRNA(Asn), MTTN). Muscle
      biopsy studies showed COX-negative, SDH-positive fibers at histochemistry and
      biochemical defects of oxidative metabolism. The m.5669G>A mutation was present
      only in patient's muscle resulting in the first muscle-specific MTTN mutation. Mt
      tRNA(Asn) steady-state levels and in silico predictions supported the
      pathogenicity of this mutation. A mitochondrial myopathy should be considered in
      the differential diagnosis of exercise intolerance in children.

PMID- 21741369
TI  - A Tunisian patient with Pearson syndrome harboring the 4.977kb common deletion
      associated to two novel large-scale mitochondrial deletions.
AB  - Pearson syndrome (PS) is a multisystem disease including refractory anemia,
      vacuolization of marrow precursors and pancreatic fibrosis. The disease starts
      during infancy and affects various tissues and organs, and most affected children
      die before the age of 3years. Pearson syndrome is caused by de novo large-scale
      deletions or, more rarely, duplications in the mitochondrial genome. In the
      present report, we described a Pearson syndrome patient harboring multiple
      mitochondrial deletions which is, in our knowledge, the first case described and
      studied in Tunisia. In fact, we reported the common 4.977kb deletion and two
      novel heteroplasmic deletions (5.030 and 5.234kb) of the mtDNA. These deletions
      affect several protein-coding and tRNAs genes and could strongly lead to defects
      in mitochondrial polypeptides synthesis, and impair oxidative phosphorylation and
      energy metabolism in the respiratory chain in the studied patient.

PMID- 21741370
TI  - COMMD1 regulates the delta epithelial sodium channel (deltaENaC) through
      trafficking and ubiquitination.
AB  - The delta subunit of the epithelial sodium channel (deltaENaC) is a member of the
      ENaC/degenerin family of ion channels. deltaENaC is distinct from the related
      alpha-, beta- and gammaENaC subunits, known for their role in sodium homeostasis
      and blood pressure control, as deltaENaC is expressed in brain neurons and
      activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was
      previously found to associate with and downregulate deltaENaC activity. Here, we
      show that COMMD1 interacts with deltaENaC through its COMM domain. Co-expression
      of deltaENaC with COMMD1 significantly reduced deltaENaC surface expression, and
      led to an increase in deltaENaC ubiquitination. Immunocytochemical and confocal
      microscopy studies show that COMMD1 promoted localization of deltaENaC to the
      early/recycling endosomal pool where the two proteins were localized together.
      These results suggest that COMMD1 downregulates deltaENaC activity by reducing
      deltaENaC surface expression through promoting internalization of surface
      deltaENaC to an intracellular recycling pool, possibly via enhanced
      ubiquitination.

PMID- 21741371
TI  - Discovery of a novel COX-2 inhibitor as an orally potent anti-pyretic and anti
      inflammatory drug: design, synthesis, and structure-activity relationship.
AB  - Cyclooxygenase (COX) has been considered as a significant pharmacological target
      because of its pivotal roles in the prostaglandin biosynthesis and following
      cascades that lead to various (patho)physiological effects. Non-steroidal anti
      inflammatory drugs (NSAIDs) that suppress COX activities have been used
      clinically for the treatment of fever, inflammation, and pain; however,
      nonselective COX inhibitors exhibit serious side-effects such as gastrointestinal
      damage because of their inhibitory activities against COX-1. Thus, COX-1 is
      constitutive and expressed ubiquitously and serves a housekeeping role, while COX
      2 is inducible or upregulated by inflammatory/injury stimuli such as interleukin
      1beta, tumor necrosis factor-alpha, and lipopolysaccharide in macrophage,
      monocyte, synovial, liver, and lung, and is associated with prostaglandin E2 and
      prostacyclin production that evokes or sustains systemic/peripheral inflammatory
      symptoms. Also, hypersensitivity of aspirin is a significant concern clinically.
      Hence, design, synthesis, and structure-activity relationship of [2-{[(4
      substituted)-pyridin-2-yl]carbonyl}-(6- or 5-substituted)-1H-indol-3-yl]acetic
      acid analogues were investigated to discover novel acid-type COX-2 inhibitor as
      an orally potent new-class anti-pyretic and anti-inflammatory drug. As
      significant findings, compounds 1-3 demonstrated potent COX-2 inhibitory
      activities with high selectivities for COX-2 over COX-1 in human cells or whole
      blood in vitro, and demonstrated orally potent anti-pyretic activity against
      lipopolysaccharide-induced systemic-inflammatory fever model in F344 rats. Also
      compound 1 demonstrated orally potent anti-inflammatory activity against edema
      formation and a suppressive effect against PGE2 production in carrageenan-induced
      peripheral-inflammation model on the paw of SD rats. These results suggest that
      compounds 1-3 are potential agents for the treatment of inflammatory disease and
      are useful for further pharmacological COX-2 inhibitor investigations.

PMID- 21741372
TI  - A novel parthenin analog exhibits anti-cancer activity: activation of apoptotic
      signaling events through robust NO formation in human leukemia HL-60 cells.
AB  - This study describes the anti-cancer activity of P19, an analog of parthenin. P19
      induced apoptosis in HL-60 cells and inhibited cell proliferation with 48h IC50
      of 3.5MUM. At 10mg/kg dose, it doubled the median survival time of L1210 leukemic
      mice and at 25mg/kg it inhibited Ehrlich ascites tumor growth by 60%.
      Investigation of the mechanism of P19 induced apoptosis in HL-60 cells revealed
      that N-acetyl-l-cysteine (NAC) and s-methylisothiourea (sMIT) could reverse
      several molecular events that lead to cell death by inhibiting nitric oxide (NO)
      formation. It selectively produced massive NO in cells while quenching the basal
      ROS levels with concurrent elevation of GSH. P19 disrupted mitochondrial
      integrity leading to cytochrome c release and caspase-9 activation. P19 also
      caused caspase-8 activation by selectively elevating the expression of DR4 and
      DR5. All these events lead to the activation of caspase-3 leading to PARP-1
      cleavage and DNA fragmentation. However, knocking down of AIF by siRNA also
      suppressed the apoptosis substantially thus indicating caspase independent
      apoptosis, too. Further, contrary to enhanced iNOS expression, its transcription
      factor, NF-kappaB (p65) was cleaved with a simultaneous increase in cytosolic
      IkappaB-alpha. In addition, P19 potently inhibited pro-survival proteins pSTAT3
      and survivin. The multi-modal pro-apoptotic activity of P19 raises its potential
      usefulness as a promising anti-cancer therapeutic.

PMID- 21741373
TI  - Antigen detection assay with parasite specific monoclonal antibodies for
      diagnosis of lymphatic filariasis.
AB  - BACKGROUND: Lymphatic filariasis is a painful and profoundly disfiguring disease.
      Infection is usually acquired in childhood but its visible manifestations occur
      later in life, causing temporary or permanent disability. The importance of
      developing effective assays to diagnose, monitor and evaluate human lymphatic
      filariasis has been emphasized by the WHO. METHODS: High-affinity monoclonal
      antibodies (mAbs) specific for recombinant filarial antigen WbSXP-1 were
      developed. An ELISA based capture assay using monoclonal and polyclonal
      antibodies for WbSXP-1 was used for detection of circulating filarial antigen.
      RESULTS: High-affinity monoclonal antibodies (mAbs) were developed that
      specifically binds both W. bancrofti and B. malayi mf antigens. Two mAbs (1F6H3
      and 2E12E3) of subclass IgG2a and IgM showed high affinity, avidity and
      reactivity to recombinant and mf native antigen. Both the mAbs were used in
      combination as capture antibodies and polyclonal as detection antibody to develop
      the assay. The assay showed very high sensitivity towards W. bancrofti mf
      positive samples compared to endemic normal samples (P<0.0001). CONCLUSION: A
      capture assay using high-affinity monoclonal antibodies for WbSXP-1 was developed
      for the detection of filarial circulating antigen in clinical samples from
      bancroftian infection. Besides, this would also help in epidemiological studies
      in endemic areas of filarial infections.

PMID- 21741374
TI  - Detection of synthetic cannabinoids in herbal incense products.
AB  - OBJECTIVE: We investigated the ability of clinical drug of abuse tests to detect
      synthetic cannabinoids. RESULTS: A broad class GC/MS drug screening method
      detected JWH-018 and JWH-073 in methanolic extracts and teas steeped from herbal
      incense products in three of four products tested. CONCLUSIONS: Synthetic
      cannabinoids are present in herbal incense purchased over the internet.

PMID- 21741375
TI  - An essential role for transcription before the MBT in Xenopus laevis.
AB  - Most zygotic genes remain transcriptionally silent in Drosophila, Xenopus, and
      zebrafish embryos through multiple mitotic divisions until the midblastula
      transition (MBT). Several genes have been identified in each of these organisms
      that are transcribed before the MBT, but whether precocious expression of
      specific mRNAs is important for later development has not been examined in
      detail. Here, we identify a class of protein coding transcripts activated before
      the MBT by the maternal T-box factor VegT that are components of an established
      transcriptional regulatory network required for mesendoderm induction in Xenopus
      laevis, including the Nodal related ligands xnr5, xnr6, and derriere and the
      transcription factors bix4, and sox17alpha. Accumulation of phospho-Smad2, a
      hallmark of active Nodal signaling, at the onset of the MBT requires preMBT
      transcription and activity of xnr5 and xnr6. Furthermore, preMBT activation of
      the Nodal pathway is essential for mesendodermal gene expression and patterning
      of the embryo. Finally, xnr5 and xnr6 can also activate their own expression
      during cleavage stages, indicating that preMBT transcription contributes to a
      feed-forward system that allows robust activation of Nodal signaling at the MBT.

PMID- 21741376
TI  - Chromatin and transcriptional signatures for Nodal signaling during endoderm
      formation in hESCs.
AB  - The first stages of embryonic differentiation are driven by signaling pathways
      hardwired to induce particular fates. Endoderm commitment is controlled by the
      TGF-beta superfamily member, Nodal, which utilizes the transcription factors,
      SMAD2/3, SMAD4 and FOXH1, to drive target gene expression. While the role of
      Nodal is well defined within the context of endoderm commitment, mechanistically
      it is unknown how this signal interacts with chromatin on a genome wide scale to
      trigger downstream responses. To elucidate the Nodal transcriptional network that
      governs endoderm formation, we used ChIP-seq to identify genomic targets for
      SMAD2/3, SMAD3, SMAD4, FOXH1 and the active and repressive chromatin marks,
      H3K4me3 and H3K27me3, in human embryonic stem cells (hESCs) and derived endoderm.
      We demonstrate that while SMAD2/3, SMAD4 and FOXH1 associate with DNA in a highly
      dynamic fashion, there is an optimal bivalent signature at 32 gene loci for
      driving endoderm commitment. Initially, this signature is marked by both H3K4me3
      and H3K27me3 as a very broad bivalent domain in hESCs. Within the first 24h,
      SMAD2/3 accumulation coincides with H3K27me3 reduction so that these loci become
      monovalent marked by H3K4me3. JMJD3, a histone demethylase, is simultaneously
      recruited to these promoters, suggesting a conservation of mechanism at multiple
      promoters genome-wide. The correlation between SMAD2/3 binding, monovalent
      formation and transcriptional activation suggests a mechanism by which SMAD
      proteins coordinate with chromatin at critical promoters to drive endoderm
      specification.

PMID- 21741377
TI  - High-resolution, three-dimensional mapping of gene expression using
      GeneExpressMap (GEM).
AB  - The analysis of temporal and spatial patterns of gene expression is critically
      important for many kinds of developmental studies, including the construction of
      gene regulatory networks. Recently, multiplex, fluorescent, whole mount in situ
      hybridization (multiplex F-WMISH), applied in combination with confocal
      microscopy, has emerged as the method of choice for high-resolution, three
      dimensional (3D) mapping of gene expression patterns in developing tissues. We
      have developed an image analysis tool, GeneExpressMap (GEM), that facilitates the
      rapid, 3D analysis of multiplex F-WMISH data at single-cell resolution. GEM
      assigns F-WMISH signal to individual cells based upon the proximity of
      cytoplasmic hybridization signal to cell nuclei. Here, we describe the features
      of GEM and, as a test of its utility, we use GEM to analyze patterns of
      regulatory gene expression in the non-skeletogenic mesoderm of the early sea
      urchin embryo. GEM greatly extends the power of multiplex F-WMISH for analyzing
      patterns of gene expression and is a valuable tool for gene network analysis and
      many other kinds of developmental studies.

PMID- 21741378
TI  - Exploring the potential of telmisartan in chronic constriction injury-induced
      neuropathic pain in rats.
AB  - The present study was designed to investigate the potential of telmisartan, an
      angiotensin AT(1) receptor, in chronic constriction injury-induced neuropathic
      pain in rats. Four loose ligatures were placed around the sciatic nerve to induce
      chronic constriction injury and neuropathic pain. Acetone drop, pin-prick, hot
      plate and paint brush tests were performed to assess cold allodynia; mechanical
      and heat hyperalgesia; and dynamic mechanical allodynia, respectively along with
      assessment of spontaneous pain and postural index in terms of foot deformity. The
      levels of TNF-alpha were measured in the sciatic nerve as an index of
      inflammation. Chronic constriction injury was associated with development of cold
      allodynia; mechanical and heat hyperalgesia; dynamic mechanical allodynia; and
      spontaneous pain and foot deformity along with rise in the levels of TNF-alpha.
      Telmisartan (1, 2, 5 mg/kg, p.o.) was administered for 14 days in chronic
      constriction injury subjected rats. Administration of telmisartan (2, 5 mg/kg)
      significantly attenuated chronic constriction injury-induced pain related
      behavior, foot deformity and rise in TNF-alpha level. It may be concluded that
      telmisartan has a potential in attenuating neuropathic pain behavior in chronic
      constriction injury model which may possibly be attributed to its anti
      inflammatory properties.

PMID- 21741379
TI  - A new assay for functional screening of BRCA2 linker region mutations identifies
      variants that alter chemoresistance to cisplatin.
AB  - Variants of unknown significance (VUS) complicate the assignment of risk to new
      DNA sequence variants found in at-risk populations. This study focused on the
      poorly studied linker region of the cancer-associated BRCA2 protein encoded by
      exons twelve through fourteen of BRCA2. To develop a new method to characterize
      VUS in this region of BRCA2, we first chose to study 4 reported VUS occurring on
      evolutionarily conserved residues within the linker region. To determine if these
      VUS represent neutral changes or if they impact the function of the BRCA2
      protein, we stably transfected expression plasmids encoding wild-type or each
      mutant peptide into T47D breast cancer cells, which are wild-type for BRCA2. Four
      mutant peptide expressing cell lines and a wild-type linker region expressing
      cell line next were studied by challenging transfected cell lines with the DNA
      crosslinking compound cisplatin (10MUM) for 5days. Expression of the wild-type
      linker region and certain mutant linker peptides (N2452D and I2285V) decreased
      apoptosis (as demonstrated by cell death detection assay) in transfected cell
      lines, indicating that the linker region peptide directly or indirectly affects
      the DNA damage repair pathway. By determining the cell survival and assaying the
      apoptotic index of treated cell lines, one could potentially use this screen to
      determine that a particular VUS has a functional impact on BRCA2 function, and
      hence is of functional significance. We conclude that this method is useful for
      screening the effect of linker region VUS on BRCA2 function, and to identify
      mutations for further testing. We also conclude that mutations in the linker
      region may have heretofore unappreciated roles in BRCA2 function.

PMID- 21741380
TI  - Toxoplasma gondii isolates: multilocus RFLP-PCR genotyping from human patients in
      Sao Paulo State, Brazil identified distinct genotypes.
AB  - This study investigated the genetic characteristics of Toxoplasma gondii samples
      collected from 62 patients with toxoplasmosis in Sao Paulo State, Brazil. DNA
      samples were isolated from blood, cerebrospinal fluid and amniotic fluids of 25
      patients with cerebral toxoplasmosis and AIDS, two patients with acute
      toxoplasmosis, 12 patients with ocular toxoplasmosis, six newborns with
      congenital toxoplasmosis and 17 pregnant women with acute infection. Diagnosis of
      toxoplasmosis was based in clinical, radiological and laboratory features.
      Genotyping was performed using multilocus PCR-RFLP genetic markers including
      SAG1, SAG2, 5'- and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, C22-8, c29-2, L358, PK1
      and Apico. Among the 62 clinical samples, 20 (32%) were successfully genotyped at
      eight or more genetic loci and were grouped to three distinct genotypes. Eighteen
      samples belonged to ToxoDB Genotype #65 and the other two samples were identified
      as ToxoDB Genotypes #6 and #71, respectively (http://toxodb.org/toxo/). Patients
      presenting Genotypes #6 and #71 had severe and atypical cerebral toxoplasmosis,
      characterized by diffuse encephalitis without extensive brain lesions. These
      results indicate that T. gondii Genotype #65 may have a high frequency in causing
      human toxoplasmosis in Sao Paulo State, Brazil. This unusual finding highlights
      the need to investigate the possible association of parasite genotypes with human
      toxoplasmosis.

PMID- 21741381
TI  - Expression of leptin-like peptide (LLP) mRNA in channel catfish (Ictalurus
      punctatus) is induced by exposure to Edwardsiella ictaluri but is independent of
      energy status.
AB  - Leptin is a key pleiotropic cytokine involved in regulation of energy homeostasis
      and immunity in mammals. In channel catfish, the presence of a partial messenger
      RNA sequence that encodes a leptin-like peptide (LLP) has been identified and
      investigated. The objectives of the present studies were to clone and
      characterize full-length catfish LLP gene, examine tissue expression of LLP mRNA,
      and determine effects of prolonged fasting and exposure to Edwardsiella ictaluri
      (E. ictaluri), the bacteria that causes enteric septicemia in catfish, on LLP
      mRNA expression. Full-length catfish LLP gene was sequenced by genome walking and
      by 5'- and 3'-RACE. Catfish LLP gene contained three exons with the coding region
      located in exons 2 and 3. The amino acid sequence of the channel catfish LLP
      shared very low sequence similarities with leptin of other fish species or the
      mammalian leptin (24-49%). Using real-time polymerase chain reaction, LLP mRNA
      expression was detected in various tissues including brain, stomach, spleen,
      heart, liver, and trunk kidney and was especially high in the liver and trunk
      kidney. Expression of LLP mRNA in liver and brain was similar between fish that
      were fasted for 30days and those that received feed daily for 30days (P>0.10).
      Expression of LLP mRNA was increased in liver, spleen, and trunk kidney within
      48h post-exposure to E. ictaluri compared to unexposed fish (P<0.05). Based on
      the results of the current studies, amino acid sequence of catfish LLP is highly
      dissimilar to mammalian and fish leptin. Unlike in most mammals, catfish LLP
      expression is independent of energy status. However, the expression of catfish
      LLP is increased after exposure to pathogenic bacteria, which is similar to
      mammals. Further investigations are required to clearly define the biological
      function and regulation of catfish LLP.

PMID- 21741382
TI  - Acute and chronic stress-like levels of cortisol inhibit the oestradiol stimulus
      to induce sexual receptivity but have no effect on sexual attractivity or
      proceptivity in female sheep.
AB  - Stress-like levels of cortisol inhibit sexual receptivity in ewes but the
      mechanism of this action is not understood. One possibility is that cortisol
      interferes with the actions of oestradiol to induce sexual receptivity. We tested
      this hypothesis in 2 experiments with ovariectomised ewes that were artificially
      induced into oestrus by 12 days of i.m. injections of progesterone followed by an
      i.m. injection of oestradiol benzoate (ODB) 48 h later. In Experiment 1, ewes
      were randomly allocated to the following groups: saline infusion+25 MUg ODB,
      saline infusion+50 MUg ODB, cortisol infusion+25 MUg ODB or cortisol infusion+50
      MUg ODB (n=5 per group). Saline or cortisol was infused i.v. for 40 h beginning
      at the ODB injection. In Experiment 2, ewes were infused with saline or cortisol
      (n=5 per group) for 5h beginning 1h before ODB injection. In both experiments,
      ewe sexual behaviour (attractivity, proceptivity and receptivity) was quantified
      every 6h. Blood samples were also collected. The cortisol infusion yielded plasma
      concentrations of cortisol similar to those seen during psychosocial stress. In
      both experiments, cortisol suppressed receptivity index (number of
      immobilisations by ewe/courtship displays by ram) and the number of times ewes
      were mounted but had no effect on attractivity or proceptivity, irrespective of
      the dose of ODB (Experiment 1). Cortisol also suppressed LH pulse amplitude.
      These results suggest that both an acute (5h) and chronic (40 h) infusion of
      cortisol inhibit oestradiol-induced sexual receptivity in ewes and that
      increasing the dose of ODB does not overcome the inhibitory effects of cortisol.

PMID- 21741383
TI  - Comparison of novel methods for predicting the risk of pro-inflammatory clinical
      infusion reactions during monoclonal antibody therapy.
AB  - Two methods for predicting the risk of pro-inflammatory clinical infusion
      reactions during monoclonal antibody therapy were evaluated. In the first, the
      antibody of interest is immobilised by air-drying onto 96-well plates prior to
      the addition of human peripheral blood mononuclear cells (PBMCs). In the second,
      the antibody is added in aqueous phase to a co-culture of human PBMCs and human
      endothelium-derived cells. In both methods the cells are incubated with the
      antibody to allow the accumulation of pro-inflammatory cytokines, quantified by
      enzyme-linked immunosorbent assay (ELISA). The antibodies associated with
      clinical infusion reactions, Herceptin, Campath-1H and TGN1412, gave the largest
      responses taking into account the data for all readouts (tumour necrosis factor
      alpha, TNF, interleukin-6, IL-6, IL-8, IL-2 and cell proliferation) for both
      methods. Overall, the antibodies tested could be ranked as follows:
      Tysabri<Avastin<Herceptin<Campath-1H<TGN1412, with only the "superagonistic" CD28
      monoclonal antibody (TGN1412) stimulating IL-2 release and cell proliferation.

PMID- 21741384
TI  - A filtration-based protocol to isolate human plasma membrane-derived vesicles and
      exosomes from blood plasma.
AB  - The methods of Plasma Membrane-derived Vesicle (PMV) isolation and quantification
      vary considerably in the literature and a new standard needs to be defined. This
      study describes a novel filtration method to isolate PMVs in plasma, which avoids
      high speed centrifugation, and to quantify them using a Becton Dickinson (BD)
      FACS CaliburTM flow cytometer, as annexin V-positive vesicles, larger than 0.2
      MUm in diameter. Essentially microvesicles (which comprise a mixture of PMVs and
      exosomes) from citrate plasma were sonicated to break up clumped exosomes, and
      filtered using Millipore 0.1 MUm pore size Hydrophilic Durapore membranes in
      Swinnex 13 mm filter holders. Phosphatidylserine-positive PMVs detected with
      annexin V-PE were quantified using combined labelling and gating strategies in
      conjunction with Polysciences Polybead Microspheres (0.2 MUm) and BDTrucount
      tubes. The PMV absolute count was calculated on the analysis template using the
      Trucount tube lot number information and expressed in PMV count/ml. Having
      estimated a normal reference range (0.51*10(5)-2.82*10(5) PMVs/ml) from a small
      sample of human donors, using the developed method, the effect of certain
      variables was investigated. Variations such as freezing of samples and gender
      status did not significantly alter the PMV absolute count, and with age plasma
      PMV levels were only marginally reduced. Smokers appeared to have reduced PMV
      levels. Nicotine, as for calpeptin was shown to dose-dependently (from 10 up to
      50 MUM) reduce levels of early apoptosis in THP-1 monocytes and to decrease the
      level of PMV release. Fasting individuals had 2-3 fold higher PMV absolute counts
      compared to non-fasting subjects.

PMID- 21741385
TI  - Isolation of functional single domain antibody by whole cell immunization:
      implications for cancer treatment.
AB  - Carcinoembryonic antigen related cell adhesion molecule (CEACAM) 6 is over
      expressed in different types of cancer cells. In addition, it has also been
      implicated in some infectious diseases. Targeting this molecule by an antibody
      might have applications in diverse tumor models. Single domain antibody (sdAb) is
      becoming very useful format in antibody engineering as potential tools for
      treating acute and chronic disease conditions such as cancer for both diagnostic
      as well as therapeutic application. Generally, sdAbs with good affinity are
      isolated from an immune library. Discovery of a new target antigen would require
      a new immunization with purified antigen which is not always easy. In this study,
      we have isolated, by phage display, an sdAb against CEACAM6 with an affinity of 5
      nM from a llama immunized with cancer cells. The antibody has good biophysical
      properties, and it binds to the cells expressing the target antigen. Furthermore,
      it reduces cancer cells proliferation in vitro and shows an excellent tumor
      targeting in vivo. This sdAb could be useful in diagnosis as well as therapy of
      CEACAM6 expressing tumors. Finally, we envisage it would be feasible to isolate
      good sdAbs against other interesting tumor associated antigens from this library.
      Therefore, this immunization method could be a general strategy for isolating
      sdAbs against any surface antigen without immunizing the animal with the antigen
      of interest each time.

PMID- 21741386
TI  - Susceptibility of mosquito and lepidopteran cell lines to the mosquito iridescent
      virus (IIV-3) from Aedes taeniorhynchus.
AB  - Mosquito iridescent viruses (MIV) are members of the genus Chloriridovirus that
      currently contains only the type IIV-3 from Aedestaeniorhynchus. The complete
      genome of invertebrate iridescent virus -3 (IIV-3) has been sequenced and the
      availability of a tissue culture system would facilitate functional genomic
      studies. This investigation, using quantitative PCR and electron microscopy, has
      determined that the mosquito cell lines Aedes aegypti (Aag2), Aedes albopictus
      (C6/36) and Anopheles gambiae (4a3A) as well as the lepidopteran cell line from
      Spodoptera frugiperda (SF9) are permissive to IIV-3 infection. However, IIV-3
      infection remained longer in Aag2 and C6/36 cells. Virus produced in C6/36 cell
      line was infectious to larvae of A. taeniorhynchus by injection and per os.
      Ultrastructural examination of 4a3A and SF9 cells infected with IIV-3 revealed an
      unusual feature, where virions were localized to mitochondria. It is speculated
      that containment with mitochondria may play a role in the lack of persistence in
      these cell lines.

PMID- 21741387
TI  - New record of nucleopolyhedroviruses in tea looper caterpillars in India.
AB  - Tea production in North-East India hit a record loss due to the widespread severe
      outbreak of a mixed brood of three species of looper caterpillar pests of
      geometrid moths (Lepidoptera) in 2008-2010. In addition to Buzura suppressaria,
      two newly recorded geometrids, viz., Hyposidra infixaria and Hyposidra talaca
      have caused widespread severe damage in recent years. In the present study we
      report the nucleopolyhedroviruses (NPV) isolated from the tea looper caterpillar
      from North-East India. We identified and characterized the NPV by cloning and
      sequencing a partial segment of polyhedrin gene of virus infected larvae of B.
      suppressaria, H. talaca and H. infixaria. A comparison of deduced amino acids of
      polyhedrin gene among H. talaca, H. infixaria and B. suppressaria showed that
      same strain was found to infect all the three loopers in India, which show high
      sequence identity with B. suppressaria Chinese isolates. Based on the polyhedrin
      sequence homology, it is predicted that a variant of B. suppressaria Chinese
      isolate of NPV found to infect H. talaca, H. infixaria and B. suppressaria in
      India.

PMID- 21741388
TI  - Anatomical and molecular mapping of the left and right ventricular His-Purkinje
      conduction networks.
AB  - Functioning of the cardiac conduction system depends critically on its structure
      and its complement of ion channels. Therefore, the aim of this study was to
      document both the structure and ion channel expression of the left and right
      ventricular His-Purkinje networks, as we have previously done for the sinoatrial
      and atrioventricular nodes. A three-dimensional (3D) anatomical computer model of
      the His-Purkinje network of the rabbit heart was constructed after staining the
      network by immunoenzyme labelling of a marker protein, middle neurofilament. The
      bundle of His is a ribbon-like structure and the architecture of the His-Purkinje
      network differs between the left and right ventricles. The 3D model is able to
      explain the breakthrough points of the action potential on the ventricular
      epicardium during sinus rhythm. Using quantitative PCR, the expression levels of
      the major ion channels were measured in the free running left and right Purkinje
      fibres of the rabbit heart. Expression of ion channels differs from that of the
      working myocardium and can explain the specialised electrical activity of the
      Purkinje fibres as suggested by computer simulations; the expression profile of
      the left Purkinje fibres is more specialised than that of the right Purkinje
      fibres. The structure and ion channel expression of the Purkinje fibres are
      highly specialised and tailored to the functioning of the system. The His
      Purkinje network in the left ventricle is more developed than that in the right
      ventricle and this may explain its greater clinical importance.

PMID- 21741389
TI  - Activation of endothelial nitric oxide synthase is dependent on its interaction
      with globular actin in human umbilical vein endothelial cells.
AB  - Endothelial nitric oxide synthase (eNOS) has been reported to associate with
      globular actin, and this association increases eNOS activity. Adenosine,
      histamine, salbutamol and thrombin cause activation of eNOS through widely
      different mechanisms. Whether these eNOS agonists can regulate eNOS activity
      through affecting its association with actin is unknown. As previously reported,
      we confirmed in cultured human umbilical vein endothelial cells (HUVEC) that
      histamine and thrombin increased intracellular Ca(2+) whereas adenosine and
      salbutamol did not, and that these four agonists caused different effects on
      actin filament structure. Nevertheless, despite their divergent effects on
      intracellular Ca(2+) and on actin filament structure, we found by
      immunoprecipitation that adenosine, histamine, salbutamol and thrombin all caused
      an increase in association between eNOS and globular actin. This increase of
      association was inhibited by pre-treatment with phalloidin, an actin filament
      stabilizer. All of these agonists also increased phosphorylation of eNOS on
      serine residue 1177, eNOS activity, and cyclic guanosine-3', 5'-monophosphate,
      and these increases were all attenuated by phalloidin. Agonist-induced
      phosphorylation of eNOS on serine 1177 was attenuated by Akt inhibition, whereas
      association of eNOS with actin was not. We also found, in HEK-293 cells
      transfected with the eNOS mutants eNOS-S1177A or eNOS-S1177D, that the
      association between eNOS and globular actin was decreased as compared to cells
      transfected with wild-type eNOS. We conclude that association of globular actin
      with eNOS plays an essential and necessary role in agonist-induced eNOS
      activation, through enabling its phosphorylation by Akt at serine residue 1177.

PMID- 21741390
TI  - Molecular insights into the control of transcription initiation at the
      Staphylococcus aureus agr operon.
AB  - The accessory gene regulatory (agr) operon of the opportunistic human pathogen
      Staphylococcus aureus is a prime pathogenesis factor in this bacterium. The agr
      operon consists of two transcription units, RNAII and RNAIII, which are
      transcribed from divergent promoters, P2 and P3, respectively. RNAII encodes a
      quorum-sensing system, including AgrA, the master transcription activator of the
      agr operon. RNAIII is the effector RNA molecule that regulates the expression of
      many virulence genes. Owing to the atypical spacer lengths of P2 and P3, it is
      widely considered that transcription from P2 and P3 only occurs in a strictly
      AgrA-dependent manner. Here, using a fully native S. aureus in vitro
      transcription system, we provide the first molecular and mechanistic
      characterisation of the regulation of transcription initiation at the agr operon.
      Surprisingly, the results demonstrate that RNA polymerase (RNAp) can interact
      with P2 and P3 equally well in the absence of AgrA. However, formation of a
      transcription-competent open promoter complex (RPo) occurs more readily at P2
      than at P3 when AgrA is absent. Reducing the atypical P3 spacer region length to
      the optimal length of 17 nucleotides significantly improves promoter activity by
      facilitating the isomerisation of the initial RNAp-P3 complexes to RPo, and the
      extended -10-like element of P3 is required for optimal promoter activity. AgrA
      increases the occupancy of both promoters by RNAp and thereby increases the
      amount of transcription initiated at P2 and P3. However, the AgrA-mediated effect
      on transcription initiation is more prominent at P3 that at P2. The effect of
      AgrA at P2 and P3 appears to be restricted to events leading to the formation of
      RPo. The relevance of AgrA-independent and AgrA-dependent transcription
      initiation at P2 and P3 is presented in the context of our current understanding
      of the role of the agr operon in the pathobiology of S. aureus.

PMID- 21741391
TI  - Parameter estimation and change-point detection from Dynamic Contrast Enhanced
      MRI data using stochastic differential equations.
AB  - Dynamic Contrast Enhanced imaging (DCE-imaging) following a contrast agent bolus
      allows the extraction of information on tissue micro-vascularization. The dynamic
      signals obtained from DCE-imaging are modeled by pharmacokinetic compartmental
      models which integrate the Arterial Input Function. These models use ordinary
      differential equations (ODEs) to describe the exchanges between the arterial and
      capillary plasma and the extravascular-extracellular space. Their least squares
      fitting takes into account measurement noises but fails to deal with
      unpredictable fluctuations due to external/internal sources of variations
      (patients' anxiety, time-varying parameters, measurement errors in the input
      function, etc.). Adding Brownian components to the ODEs leads to stochastic
      differential equations (SDEs). In DCE-imaging, SDEs are discretely observed with
      an additional measurement noise. We propose to estimate the parameters of these
      noisy SDEs by maximum likelihood, using the Kalman filter. In DCE-imaging, the
      contrast agent injected in vein arrives in plasma with an unknown time delay. The
      delay parameter induces a change-point in the drift of the SDE and ODE models,
      which is estimated also. Estimations based on the SDE and ODE pharmacokinetic
      models are compared to real DCE-MRI data. They show that the use of SDE provides
      robustness in the estimation results. A simulation study confirms these results.

PMID- 21741392
TI  - Retinal transfer of nicotinate by H+ -monocarboxylate transporter at the inner
      blood-retinal barrier.
AB  - Nicotinic acid is a constituent of the coenzymes NAD and NADP. It also serves as
      an agonist for the G-protein-coupled receptor GPR109A. Nicotinic acid is widely
      used at high doses as a lipid-lowering drug, which is associated with an ocular
      side effect known as niacin maculopathy. Here we investigated the mechanism by
      which nicotinate is transferred into retina across the inner blood-retinal
      barrier (BRB). In vivo the blood-to-retina transport of [(3)H]-nicotinate was
      studied using the carotid artery injection technique. The characteristics of
      nicotinate transport at the inner BRB were examined in a conditionally
      immortalized rat retinal capillary endothelial cell line (TR-iBRB2), an in vitro
      model of inner BRB. The expression of transporters in TR-iBRB2 cells was
      determined by reverse transcription-polymerase chain reaction. In vivo [(3)H]
      nicotinate uptake by the retina was 5.4-fold greater than that of [(14)C]
      sucrose, a BRB impermeable vascular space marker. Excess amounts of unlabeled
      nicotinate and salicylate significantly decreased the in vivo retinal uptake of
      [(3)H]-nicotinate. [(3)H]-Nicotinate was taken up by TR-iBRB2 cells via an H(+)
      dependent saturable process with a Michaelis constant of ~7 mM. Na(+) had minimal
      effect on the uptake. The H(+)-dependent uptake was significantly inhibited by
      endogenous monocarboxylates such as lactate and pyruvate, and monocarboxylic
      drugs such as valproate, salicylate, and ibuprofen. These characteristics are
      consistent with those of H(+)-coupled monocarboxylate transporters (MCTs). MCT1,
      MCT2, and MCT4 mRNAs were expressed in TR-iBRB2 cells. The Na(+)-dependent
      monocarboxylate transporters SMCT1 and SMCT2 were not expressed in these cells.
      In conclusion, transfer of nicotinate from blood to retina across the inner BRB
      occurs primarily via H(+)-coupled monocarboxylate transporters.

PMID- 21741393
TI  - Endothelin-1 levels predict endothelial progenitor cell mobilization after acute
      myocardial infarction.
AB  - INTRODUCTION: Endothelin-1 (ET-1), circulating endothelial cells (CEC) and
      endothelial progenitor cells (EPC) are well-known modulators of endothelial
      function with important cardiac effects after an acute myocardial infarction.
      However, the relationship between them has never been assessed. The objective of
      the present study was to establish the relationship between ET-1, CEC, and EPC
      concentrations after ST-elevation myocardial infarction (STEMI). METHODS:
      Endothelin-1, CEC, and EPC levels were measured in 61 patients presenting with a
      first STEMI. Samples were withdrawn acutely 6-24h and 1week after admission.
      Assessments included reperfusion outcomes (angiography), left ventricular
      ejection fraction (echocardiography), and 30-day mortality. RESULTS: Mean age was
      60.6+/-12.6years and 45 (74%) were males. Higher ET-1 plasma levels were
      associated with lower EPC count after 1week (7.45+/-2.53pg/ml if EPCs in the
      first quartile vs 5.72+/-1.49pg/ml if EPCs in the fourth quartile; P=0.04). In
      contrast with CEC and EPC count, higher ET-1 concentrations on admission were
      associated with Killip>=2 (9.92+/-2.01pg/ml vs 7.32+/-2.13pg/ml; P<0.001), post
      reperfusion thrombolysis in myocardial infarction (TIMI) <3 (8.65+/-2.86pg/ml vs
      5.87+/-1.93pg/ml; P=0.002), myocardial blush grade (MBG) <3 (7.46+/-2.48pg/ml vs
      5.99+/-2.01pg/ml; P=0.004) and higher 30-day mortality (10.29+/-2.02pg/ml vs
      6.57+/-2.20pg/ml; P=0.005). CONCLUSIONS: In STEMI patients, high ET-1 levels on
      admission predict a lower EPC mobilization after 1week. Endothelin-1 provides
      better clinical, angiographic and echocardiographic information for prognosis
      than do CEC and EPC concentrations.

PMID- 21741395
TI  - Mode of action of membrane-disruptive lytic compounds from the marine
      dinoflagellate Alexandrium tamarense.
AB  - Certain allelochemicals of the marine dinoflagellate Alexandrium tamarense cause
      lysis of a broad spectrum of target protist cells but the lytic mechanism is
      poorly defined. We first hypothesized that membrane sterols serve as molecular
      targets of these lytic compounds, and that differences in sterol composition
      among donor and target cells may cause insensitivity of Alexandrium and
      sensitivity of targets to lytic compounds. We investigated Ca(2+) influx after
      application of lytic fractions to a model cell line PC12 derived from a
      pheochromocytoma of the rat adrenal medulla to establish how the lytic compounds
      affect ion flux associated with lysis of target membranes. The lytic compounds
      increased permeability of the cell membrane for Ca(2+) ions even during blockade
      of Ca(2+) channels with cadmium. Results of a liposome assay suggested that the
      lytic compounds did not lyse such target membranes non-specifically by means of
      detergent-like activity. Analysis of sterol composition of isolates of A.
      tamarense and of five target protistan species showed that both lytic and non
      lytic A. tamarense strains contain cholesterol and dinosterol as major sterols,
      whereas none of the other tested species contain dinosterol. Adding sterols and
      phosphatidylcholine to a lysis bioassay with the cryptophyte Rhodomonas salina
      for evaluation of competitive binding indicated that the lytic compounds
      possessed apparent high affinity for free sterols and phosphatidylcholine. Lysis
      of protistan target cells was dose-dependently reduced by adding various sterols
      or phosphatidylcholine. For three tested sterols, the lytic compounds showed
      highest affinity towards cholesterol followed by ergosterol and brassicasterol.
      Cholesterol comprised a higher percentage of total sterols in plasma membrane
      fractions of A. tamarense than in corresponding whole cell fractions. We conclude
      therefore that although the molecular targets of the lytic compounds are likely
      to involve sterol components of membranes, A. tamarense must have a complex self
      protective mechanism that still needs to be addressed.

PMID- 21741394
TI  - Focal adhesion kinase regulation of mechanotransduction and its impact on
      endothelial cell functions.
AB  - Vascular endothelial cells lining the blood vessels form the interface between
      the bloodstream and the vessel wall and as such they are continuously subjected
      to shear and cyclic stress from the flowing blood in the lumen. Additional
      mechanical stimuli are also imposed on these cells in the form of substrate
      stiffness transmitted from the extracellular matrix components in the basement
      membrane, and additional mechanical loads imposed on the lung endothelium as the
      result of respiration or mechanical ventilation in clinical settings. Focal
      adhesions (FAs) are complex structures assembled at the abluminal endothelial
      plasma membrane which connect the extracellular filamentous meshwork to the
      intracellular cytoskeleton and hence constitute the ideal checkpoint capable of
      controlling or mediating transduction of bidirectional mechanical signals. In
      this review we focus on focal adhesion kinase (FAK), a component of FAs, which
      has been studied for a number of years with regards to its involvement in
      mechanotransduction. We analyzed the recent advances in the understanding of the
      role of FAK in the signaling cascade(s) initiated by various mechanical stimuli
      with particular emphasis on potential implications on endothelial cell functions.

PMID- 21741396
TI  - Alternate-day fasting reverses the age-associated hypertrophy phenotype in rat
      heart by influencing the ERK and PI3K signaling pathways.
AB  - The age-related increased impedance in large arteries overloads the senescent
      heart, and the myocardial phenotype is hypertrophic. Together with qualitative
      changes observed in the senile heart, this can be responsible for impaired
      diastolic function. A restricted diet providing adequate nutrient intake, e.g.
      alternate-day fasting (ADF), has been shown to extend life-span and decrease
      incidence and progression of age-associated diseases in laboratory rodents, and
      to ameliorate some metabolic markers of aging in rhesus monkeys and humans. This
      study reports an age-related increase of some biological and morphological
      hypertrophy markers in the rat heart, together with increased plasma BNP, a well
      known marker of heart failure. The tissue modifications might likely be related
      to hyper-activation of two of the signaling pathways associated with myocardial
      pathological hypertrophy: ERK1/2 and PI3Kgamma. Increased ERK1/2 activation might
      be in part related to the disturbance of STAT3, with a consequent decrease of
      SOCS3. In this context, the down-modulation of ERK1/2 and PI3Kgamma signaling,
      together with the restoration of STAT3 activity and SOCS3 content, both observed
      with ADF, might help to reduce pathological hypertrophy stimuli and to rescue an
      important cardioprotective pathway, possibly opening new preventive and
      therapeutic perspectives in age-related heart failure.

PMID- 21741397
TI  - Sexual differentiation of the gonadotropin surge release mechanism: a new role
      for the canonical NfkappaB signaling pathway.
AB  - Sex differences in luteinizing hormone (LH) release patterns are controlled by
      the hypothalamus, established during the perinatal period and required for
      fertility. Female mammals exhibit a cyclic surge pattern of LH release, while
      males show a tonic release pattern. In rodents, the LH surge pattern is dictated
      by the anteroventral periventricular nucleus (AVPV), an estrogen receptor-rich
      structure that is larger and more cell-dense in females. Sex differences result
      from mitochondrial cell death triggered in perinatal males by estradiol derived
      from aromatization of testosterone. Herein we provide an historical perspective
      and an update describing evidence that molecules important for cell survival and
      cell death in the immune system also control these processes in the developing
      AVPV. We conclude with a new model proposing that development of the female AVPV
      requires constitutive activation of the Tnfalpha, Tnf receptor 2, NfkappaB and
      Bcl2 pathway that is blocked by induction of Tnf receptor-associated factor 2
      inhibiting protein (Traip) in the male.

PMID- 21741398
TI  - Cross-linked succinyl chitosan as an adsorbent for the removal of Methylene Blue
      from aqueous solution.
AB  - Removal of a basic dye (Methylene Blue) from aqueous solution was investigated
      using a cross-linked succinyl-chitosan (SCCS) as sorbent. The chemical structures
      of chitosan and its derivatives were testified by FT-IR. X-ray diffraction, DTG
      analysis and swelling measurements were conducted to clarify the characteristics
      of the chemically modified chitosan. The effect of process parameters, such as pH
      of the initial solution, and concentrations of dyes on the extent of Methylene
      Blue (MB) adsorption was investigated. The Langmuir isotherm model was used to
      fit the equilibrium experimental data, giving a maximum sorption capacity of
      289.02 mg/g at 298 K. Kinetic studies showed that the kinetic data were well
      described by the pseudo-second-order kinetic model. Thermodynamic parameters such
      as enthalpy change (DeltaH degrees ), free energy change (DeltaG degrees ) and
      entropy change (DeltaS degrees ) were determined to be -25.32 kJmol(-1), -6.76
      kJmol(-1) and -62.36 Jmol(-1) K(-1), respectively, which leads to a conclusion
      that the adsorption process is spontaneous and exothermic.

PMID- 21741399
TI  - In vitro anti-oxidant activity, fluorescence quenching study and structural
      features of carbohydrate polymers from Phyllanthus emblica.
AB  - The water-extracted carbohydrate polymers (WE) of Phyllanthus emblica are
      analyzed using chemical, chromatographic, and spectroscopic methods. Anion
      exchange-chromatography of WE yielded four fractions (F1-F4) with different
      chemical compositions and all of them contain phenolics. The major fraction F4
      possesses 50% polysaccharide and 26% phenol, and is a glycoconjugate. The
      antioxidant capacities of WE and F4 are comparable to standard anti-oxidants.
      Notably, activities of F1-F4 correlate with their phenol content. Evidence for
      the complexation of F4 with bovine serum albumin is presented by fluorescence
      quenching measurement. The results also indicate conformational change of protein
      at high carbohydrate polymer concentration.

PMID- 21741400
TI  - Investigations on the role of a lysozyme from the malaria vector Anopheles dirus
      during malaria parasite development.
AB  - A cDNA encoding a lysozyme was obtained by rapid amplification of cDNA ends
      polymerase chain reaction (RACE-PCR) from females of the malaria vector Anopheles
      dirus A (Diptera: Culicidae). The 623 bp lysozyme (AdLys c-1) cDNA encodes the
      120 amino acid mature protein with a predicted molecular mass of 13.4 kDa and
      theoretical pI of 8.45. Six cysteine residues and a potential calcium binding
      motif that are present in AdLys c-1 are highly conserved relative to those of c
      type lysozymes found in other insects. RT-PCR analysis of the AdLys c-1
      transcript revealed its presence at high levels in the salivary glands both in
      larval and adult stages and in the larval caecum. dsRNA mediated gene knockdown
      experiments were conducted to examine the potential role of this lysozyme during
      Plasmodium berghei infection. Silencing of AdLys c-1 resulted in a significant
      reduction in the number of oocysts as compared to control dsGFP injected
      mosquitoes.

PMID- 21741401
TI  - Parietal cortex matters in Alzheimer's disease: an overview of structural,
      functional and metabolic findings.
AB  - Atrophy of the medial temporal lobe, especially the hippocampus and the
      parahippocampal gyrus, is considered to be the most predictive structural brain
      biomarker for Alzheimer's Dementia (AD). However, recent neuroimaging studies
      reported a possible mismatch between structural and metabolic findings, showing
      medial temporal lobe atrophy and medial parietal hypoperfusion as biomarkers for
      AD. The role of the parietal lobe in the development of AD is only recently
      beginning to attract attention. The current review discusses parietal lobe
      involvement in the early stages of AD, viz. mild cognitive impairment, as
      reported from structural, functional, perfusion and metabolic neuroimaging
      studies. The medial and posterior parts of the parietal lobe seem to be
      preferentially affected, compared to the other parietal lobe parts. On the basis
      of the reviewed literature we propose a model showing the relationship between
      the various pathological events, as measured by different neuroimaging
      techniques, in the development of AD. In this model myelin breakdown is a
      beginning of the chain of pathological events leading to AD pathology and an AD
      diagnosis.

PMID- 21741402
TI  - BTBR T+tf/J mice: autism-relevant behaviors and reduced fractone-associated
      heparan sulfate.
AB  - BTBR T+tf/J (BTBR) mice have emerged as strong candidates to serve as models of a
      range of autism-relevant behaviors, showing deficiencies in social behaviors;
      reduced or unusual ultrasonic vocalizations in conspecific situations; and
      enhanced, repetitive self-grooming. Recent studies have described their behaviors
      in a seminatural visible burrow system (VBS); a Social Proximity Test in which
      avoidance of a conspecific is impossible; and in an object approach and
      investigation test evaluating attention to specific objects and potential
      stereotypies in the order of approaching/investigating objects. VBS results
      confirmed strong BTBR avoidance of conspecifics and in the Social Proximity Test,
      BTBR showed dramatic differences in several close-in behaviors, including
      specific avoidance of a nose-to-nose contact that may potentially be related to
      gaze-avoidance. Diazepam normalized social avoidance by BTBRs in a Three-Chamber
      Test, and some additional behaviors - but not nose to nose avoidance - in the
      Social Proximity Test. BTBR also showed higher levels of preference for
      particular objects, and higher levels of sequences investigating 3- or 4-objects
      in the same order. Heparan sulfate (HS) associated with fractal structures in the
      subventricular zone of the lateral ventricles was severely reduced in BTBR. HS
      may modulate the functions of a range of growth and guidance factors during
      development, and HS abnormalities are associated with relevant brain (callosal
      agenesis) and behavioral (reductions in sociality) changes; suggesting the value
      of examination of the dynamics of the HS system in the context of autism.

PMID- 21741403
TI  - Maternal prenatal and child organophosphate pesticide exposures and children's
      autonomic function.
AB  - BACKGROUND: Organophosphate pesticides (OP), because of their effects on
      cholinergic fibers, may interfere with the functions of the autonomic nervous
      system (ANS). We conducted a study to assess the relation of in utero and child
      OP pesticide exposures and children's autonomic nervous system (ANS)
      dysregulation under resting and challenge conditions. We hypothesized that
      children with high OP levels would show parasympathetic activation and no
      sympathetic activation during rest and concomitant parasympathetic and
      sympathetic activation during challenging conditions. METHODS: OP exposures were
      assessed by measuring urinary dialkylphosphate metabolites (DAPs, total diethyls
      DEs, and total dimethyls-DMs) in maternal and children's spot urine samples. ANS
      regulation was examined in relation to maternal and child DAPs in 149 children at
      6 months and 1 year, 97 at 3 1/2 years and 274 at 5 years. We assessed resting
      and reactivity (i.e., challenge minus rest) measures using heart rate (HR),
      respiratory sinus arrhythmia (RSA), and preejection period (PEP) during the
      administration of a standardized protocol. Cross-sectional (at each age) and
      longitudinal regression models were conducted to assess OP and ANS associations.
      To estimate cumulative exposure at 5 years, we used an area-under-the
      concentration-time-curve (AUC) methodology. We also evaluated whether children
      with consistently high versus low DAP concentrations had significantly different
      mean ANS scores at 5 years. RESULTS: Child DMs and DAPs were significantly
      negatively associated with resting RSA at 6 months and maternal DMs and child DEs
      were significantly positively associated with resting PEP at 1 year. No
      associations with resting were observed in 3 1/2- or 5-year-old children nor with
      reactivity at any age. There was no significant relationship between the
      reactivity profiles and maternal or child DAPs. Cumulative maternal total DEs
      were associated with low HR (-3.19 bpm decrease; 95% CI: -6.29 to -0.09, p=0.04)
      only at 5 years. In addition, there were no significant differences in ANS
      measures for 5-year-olds with consistently high versus low DAPs. CONCLUSION:
      Although we observe some evidence of ANS dysregulation in infancy, we report no
      consistent associations of maternal and child OP pesticide exposure, as measured
      by urinary DAPs, on children's ANS (HR, RSA, and PEP) regulation during resting
      and challenging conditions up to age 5 years.

PMID- 21741404
TI  - Regulation of myocyte enhancer factor-2 transcription factors by neurotoxins.
AB  - Various isoforms of myocyte enhancer factor-2 (MEF2) constitute a group of
      nuclear proteins found to play important roles in increasing types of cells. In
      neurons, MEF2s are required to regulate neuronal development, synaptic
      plasticity, as well as survival. MEF2s promote the survival of several types of
      neurons under different conditions. In cellular models, negative regulation of
      MEF2s by stress and toxic signals contributes to neuronal death. In contrast,
      enhancing MEF2 activity not only protects cultured primary neurons from death in
      vitro but also attenuates the loss of dopaminergic neurons in substantia nigra
      pars compacta in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine mouse model of
      Parkinson's disease. In this work, the mechanisms of regulation of MEF2 function
      by several well-known neurotoxins and their implications in various
      neurodegenerative diseases are reviewed.

PMID- 21741405
TI  - Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on brain
      structure and function: a study at 4T.
AB  - BACKGROUND: More than 100,000 US troops were potentially exposed to chemical
      warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at
      Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We
      previously found reduced total gray matter (GM) volume in 40 GW veterans with
      suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T
      MR scanner. In this study, we reexamine the relationship between GB/GF exposure
      and volumetric measurements of gross neuroanatomical structures in a different
      cohort of GW veterans on a 4T MR scanner. METHODS: Neuropsychological and
      magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War
      Illness performed between 2005 and 2010 were used in this study. 4T MRI data were
      analyzed using automated image processing techniques that produced volumetric
      measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid
      (CSF). RESULTS: Binary comparisons of 64 GB/GF exposed veterans and 64 'matched',
      unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the
      exposed veterans. Behaviorally, exposed veterans committed more errors of
      omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed
      veterans on the Continuous Performance Test (CPT), a measure sustained and
      selective attention. Regression analyses confirmed that GB/GF exposure status
      predicted GM (beta=-0.11, p=0.02) and WM (beta=-0.14, p=0.03) volumes, and number
      of CPT omission errors (beta=0.22, p=0.02) over and above potentially confounding
      demographic, clinical, and psychosocial variables. There was no dose-response
      relationship between estimated levels of GB/GF exposure and brain volume.
      However, we did find an effect of Gulf War Illness/Chronic Multisymptom Illness
      on both GM and WM volume in the GB/GF exposed veterans. CONCLUSIONS: These
      findings confirm previous reports by our group and others of central nervous
      system pathology in GW veterans with suspected exposure to low levels of GB/GF
      two decades after the exposure.

PMID- 21741406
TI  - Methylmercury (MeHg) elicits mitochondrial-dependent apoptosis in developing
      hippocampus and acts at low exposures.
AB  - The developing brain is particularly sensitive to environmental teratogens, such
      as methylmercury (MeHg), which may induce cell death. Although several mechanisms
      of MeHg-induced apoptosis have been defined in culture models, pathways mediating
      caspase-3 activation in vivo remain unclear, especially in the developing
      hippocampus. To explore apoptotic mechanisms, Sprague-Dawley rats were exposed to
      5 MUg/g MeHg or PBS vehicle on postnatal day 7 (P7) and the hippocampus was
      assessed at various times for levels of apoptotic proteins. MeHg induced a 38%
      increase in Bax protein and an increase in cytosolic cytochrome c at 4h, followed
      by later increases in caspase-9 (40% at 12h; 33% at 24h) and caspase-8 (33% at
      24h), compared to controls. MeHg also induced an increase in executioner caspase
      3, a protease activated by both mitochondrial-dependent caspase-9 and
      mitochondrial-independent caspase-8. To further define pathways, we used a
      forebrain culture model and found that the MeHg-induced increases in caspase-3
      and caspase-8 were completely blocked by a caspase-9-specific inhibitor, while
      caspase-9 induction was unperturbed by the caspase-8 inhibitor. These
      observations suggest that MeHg acts primarily through the mitochondrial-dependent
      cascade to activate caspase-3 in forebrain precursors, a pathway that may
      contribute to previously documented neurotoxicity in developing hippocampus. In
      turn, using the endpoint protein, caspase-3, as a sensitive marker for neural
      injury, we were able to detect hippocampal cell death in vivo at ten-fold lower
      levels of MeHg exposure (0.6 MUg/g) than previously reported. Thus mitochondrial
      dependent cell death in the hippocampus may serve as a sensitive index for
      teratogenic insults to the developing brain.

PMID- 21741407
TI  - Automated Facial Action Coding System for dynamic analysis of facial expressions
      in neuropsychiatric disorders.
AB  - Facial expression is widely used to evaluate emotional impairment in
      neuropsychiatric disorders. Ekman and Friesen's Facial Action Coding System
      (FACS) encodes movements of individual facial muscles from distinct momentary
      changes in facial appearance. Unlike facial expression ratings based on
      categorization of expressions into prototypical emotions (happiness, sadness,
      anger, fear, disgust, etc.), FACS can encode ambiguous and subtle expressions,
      and therefore is potentially more suitable for analyzing the small differences in
      facial affect. However, FACS rating requires extensive training, and is time
      consuming and subjective thus prone to bias. To overcome these limitations, we
      developed an automated FACS based on advanced computer science technology. The
      system automatically tracks faces in a video, extracts geometric and texture
      features, and produces temporal profiles of each facial muscle movement. These
      profiles are quantified to compute frequencies of single and combined Action
      Units (AUs) in videos, and they can facilitate a statistical study of large
      populations in disorders known to impact facial expression. We derived
      quantitative measures of flat and inappropriate facial affect automatically from
      temporal AU profiles. Applicability of the automated FACS was illustrated in a
      pilot study, by applying it to data of videos from eight schizophrenia patients
      and controls. We created temporal AU profiles that provided rich information on
      the dynamics of facial muscle movements for each subject. The quantitative
      measures of flatness and inappropriateness showed clear differences between
      patients and the controls, highlighting their potential in automatic and
      objective quantification of symptom severity.

PMID- 21741408
TI  - Rapid detection of common viruses using multi-analyte suspension arrays.
AB  - A method that uses specific oligonucleotide probes coupled to a specific array of
      fluorescent microspheres in multi-analyte suspension arrays was employed for the
      detection of common viruses, such as Herpes virus (HSV), Human papillomavirus
      (HPV) and Hepatitis B virus (HBV). Sixteen species-specific probes and 9 sets of
      specific primers were designed based on conserved sequences of these viruses in
      the GenBank database. Serial symmetric PCR, asymmetric PCR and multiple PCR
      assays were employed to evaluate the sensitivity, specificity and reproducibility
      of multi-analyte suspension arrays analyzed on a Luminex-100 analyzer instrument.
      The symmetric PCR amplification of four types of HSV, four types of HPV and HBV
      genotypes of B, C and D, combined with their corresponding species-specific
      probes and specificities were completely concordant with the results from a
      comparative sequence analyses. There was no significant difference in the median
      fluorescence intensity (MFI) value between symmetric PCR and asymmetric PCR when
      the viral DNA concentration was above 10(4)copies/test. Both PCR products were
      negative in the multi-analyte suspension arrays with viral DNA concentrations
      less than 10(3)copies/test. A multi-analyte suspension array is a flexible, high
      throughput, relatively simple method for rapid identification of common viruses
      in the clinical laboratory.

PMID- 21741409
TI  - Purification of infectious myonecrosis virus (IMNV) in species of marine shrimp
      Litopenaeus vannamei in the State of Ceara.
AB  - In Brazil, shrimp farming has been developed most intensely in the Northeast
      Region. Recently, however, exporters have become concerned over the appearance of
      Infectious Myonecrosis (IMN), the etiological agent of which is a virus called
      Infectious Myonecrosis Virus (IMNV). Although IMNV has been characterized
      extensively, purification methods are complicated to reproduce and very
      expensive. The objective of this study was to purify the IMNV virus using an easy
      reproductive method and to produce anti-IMNV antibodies to be used in diagnostic
      methods. Shrimp samples showing symptoms of IMN obtained from two aquaculture
      farms in Ceara were used for this purpose. IMNV-positive shrimps were macerated
      in phosphate buffer, pH 7.5, enriched with antioxidants, clarified with
      chloroform and the supernatant was submitted to differential centrifugation,
      precipitated using PEG and NaCl and finally loaded on a discontinuous gradient of
      sucrose. Purified IMNV was submitted to RT-PCR and electrophoresis either in
      agarose gel or SDS-PAGE, which revealed RNA and protein bands, characteristic of
      IMNV. IMNV induced humoral immune response in Swiss mice when administered
      subcutaneously. Anti-IMNV antibodies were identified by ELISA (enzyme-linked
      immunosorbent assay) and Western blotting methods and produced a response against
      purified IMNV and the crude extract obtained from the infected shrimp. However,
      antibodies specific to the crude extract obtained from uninfected shrimp were not
      detected. This is the first report of IMNV having been purified in Brazil and the
      first time that specific antibodies against IMNV proteins have been produced.
      These results suggest that easy methods can be developed to produce specific
      antiserum for viral diagnosis on a large scale.

PMID- 21741410
TI  - Packaging signals in the 5'-ends of influenza virus PA, PB1, and PB2 genes as
      potential targets to develop nucleic-acid based antiviral molecules.
AB  - In a previous study a 15-mer phosphorothioate oligonucleotide (S-ON) derived from
      the packaging signal in the 5' end of segment 1 (PB2) of influenza A virus
      (designated 5-15b) proved markedly inhibitory to virus replication. Here we
      investigated whether analogous inhibitory S-ONs targeting the 5' end of segments
      2 (PB1) and 3 (PA) could be identified and whether viral resistance to S-ONs can
      be developed. Similar to our earlier result, 20-mer S-ONs reproducing the 5' ends
      of segments 2 or 3 (complementary to the 3'-coding regions of PB1 and PA,
      respectively) exerted a powerful antiviral activity against a variety of
      influenza A virus subtypes in MDCK cells. Serial passage of the A/Taiwan/1/86
      H1N1 strain in the presence of S-ON 5-15b or its antisense as5-15b analogue
      showed that mutant viruses with reduced susceptibility to the S-ON could indeed
      be generated, although the resistant viruses displayed reduced replicative
      fitness. Sequencing the resistant viruses identified mutations in the PB1, PB2,
      PA and M1 genes. Introduction of these changes into the A/PR/8/34 H1N1 strain by
      reverse genetics, suggested that alterations to RNA function in the packaging
      regions of segments 2 and 3 were important in developing resistance to S-ON
      inhibition. However, many of the other sequence changes induced by S-ON treatment
      were markedly deleterious to virus fitness. We conclude that packaging signals in
      the influenza A virus polymerase segments provide feasible targets for nucleic
      acid-based antivirals that may be difficult for the virus to evade through
      resistance mutations.

PMID- 21741411
TI  - Bone marrow derived mesenchymal stem cell transplantation in cerebellar
      degeneration: a behavioral study.
AB  - In addition to its key role in complex motor function, the cerebellum is
      increasingly recognized to have a role in cognition. Thus, motor and cognitive
      deficits can be associated with cerebellar degeneration. After unilateral lesion
      in cerebellum (folia VI) was caused by Quinolinic acid, CM-DiI labeled
      mesenchymal stem cells (MSCs), which were isolated and purified from bone marrow,
      were transplanted into the damaged folium. Motor function was assessed using the
      cylinder test, rotarod, hanging wire and beam balance during 6 weeks after
      transplantation. Cognitive function was assessed using the Morris water maze
      learning paradigm in 3 weeks after transplantation. Six weeks after
      transplantation surviving MSCs were detectable in QA-treated animals. The MSC
      transplanted group showed markedly improved functional performance in spatial
      memory, motor learning, locomotor asymmetry, dysmetria, abnormality in
      neuromuscular strength and equilibrium 2-6 weeks compared with the controls. We
      found that cerebellar lesions produced deficits (folia VI) in motor and cognitive
      aspects of a spatial task. The results indicate that transplantation of MSCs can
      significantly reduce the behavioral abnormalities of these animals during six
      weeks after engraftment. According to results of this assay, cell therapy by
      means of bone marrow derived adult stem cells promises for treatment of
      cerebellar diseases.

PMID- 21741412
TI  - Dissociation of prefrontal cortex and nucleus accumbens dopaminergic systems in
      conditional learning in rats.
AB  - There is converging evidence that the prefrontal and mesolimbic dopaminergic
      (DAergic) systems are involved in the performance of a variety of tasks that
      require the use of contextual, or task-setting, information to select an
      appropriate response from a number of candidate responses. Performance on tasks
      of this nature are impaired in schizophrenia and in rats exposed to
      psychotomimetics; impairments that are often attenuated by administration of
      dopamine (DA) antagonists. Rats were trained on either a complex instrumental
      discrimination task, that required the use of task-setting cues, or a simple
      discrimination task that did not. Following training, microdialysis probes were
      implanted unilaterally in either the medial prefrontal cortex (mPFC) or nucleus
      accumbens (NAc) and samples were collected in freely moving animals during a
      behavioural test session. In Experiment 1, we found no difference in levels of DA
      in the mPFC of rats while they were performing the two discrimination tasks. Rats
      that performed the complex task did, however, show significantly higher mPFC DA
      levels relative to rats in the simple discrimination condition following the end
      of the behavioural test session. In Experiment 2, rats performing the conditional
      discrimination showed lower levels of DA in the NAc compared to the simple
      discrimination group both during the test session and after it. These results
      provide direct evidence that conditional discrimination tasks engage frontal and
      mesolimbic DAergic systems and are consistent with the proposal that regulation
      of fronto-striatal DA is involved in aspects of cognitive control that are known
      to be impaired in individuals with schizophrenia.

PMID- 21741413
TI  - Effects of antipsychotics and amphetamine on social behaviors in spontaneously
      hypertensive rats.
AB  - We have recently reported that spontaneously hypertensive rats (SHRs) exhibit a
      deficit in contextual fear conditioning that is specifically reversed by
      antipsychotic and potentiated by psychostimulants and other manipulations thought
      to produce schizophrenia-like states in rodents. Based on these findings, we
      suggested that this deficit in fear conditioning could be used as an experimental
      model of emotional processing impairments observed in schizophrenia. This strain
      has also been suggested as a model by which to study attention
      deficit/hyperactivity disorder (ADHD). Considering that schizophrenia and ADHD
      are both characterized by poor social function, this study aimed to investigate
      possible behavioral deficits of SHRs in a social context. Furthermore, we sought
      to examine the effects of typical and atypical antipsychotics (used for the
      treatment of schizophrenia) and a psychostimulant (used to treat ADHD) on these
      behaviors. Pairs of unfamiliar rats of the same or different (i.e., Wistar)
      strains were treated with one of the aforementioned drugs and placed in an open
      field for 10min. During this time, social behaviors, locomotion and rearing
      frequencies were scored. Atypical antipsychotics increased social interaction in
      Wistar rats (WRs) and improved the deficit in social interaction exhibited by
      SHRs. In addition, the SHR group displayed hyperlocomotion that was attenuated by
      all antipsychotics (quetiapine and clozapine also decreased locomotion in WRs)
      and potentiated by amphetamine (which also increased locomotion in WRs). Our
      results reveal that the behavioral profile of the SHR group demonstrates that
      this strain can be a useful animal model to study several aspects of
      schizophrenia.

PMID- 21741414
TI  - Genome-wide analysis of peptidase content and expression in a virulent and
      attenuated Babesia bovis strain pair.
AB  - Identifying virulence determinants in Apicomplexan parasites remains a major gap
      in knowledge for members within this phylum. We hypothesized that peptidases
      would segregate with virulence between a virulent parent Babesia bovis strain and
      an attenuated daughter strain derived by rapid in vivo passage. Using the
      complete genome sequence of the virulent T2Bo strain, 66 peptidases were
      identified and active sites confirmed. The presence, sequence identity and
      expression levels were tested for each of the 66 peptidases in the virulent
      parent and attenuated daughter T2Bo strains using whole genome, targeted
      sequencing approaches and microarrays analyses. Quantitative PCR revealed that
      there was no significant difference in peptidase expression between the virulent
      and attenuated strains. We conclude that while peptidases may well play a
      required role in B. bovis pathogenesis, neither loss of peptidase gene content
      nor reduced gene expression underlies the loss of virulence associated with in
      vivo passage and attenuation.

PMID- 21741415
TI  - Comparative role of acetylation along c-SRC/ETS1 signaling pathway in bone
      metastatic and invasive mammary cell phenotypes.
AB  - Metastatic cells switch between different modes of migration through
      supramolecular plasticity mechanism(s) still largely unknown. The aim of the
      present paper was to clarify some molecular aspects of the epigenetic control of
      migration of 1833-bone metastatic cells compared to MDA-MB231-parental mammary
      carcinoma cells. Active c-Src overexpression enhanced 1833-cell spontaneous
      migration and CXCR4-mediated chemoinvasion toward CXCL12 ligand. Only in
      metastatic cells, in fact, c-Src seemed to stabilize nuclear CXCR4-protein
      receptor possibly due to tyrosine phosphorylation, by impairing protein
      degradative smear and causing instead an electrophoretic-mobility shift; the
      cytosolic steady-state level of CXCR4 was enhanced, and the protein appeared also
      phosphorylated. These findings suggested the triggering of unique signaling
      pathways in metastasis for homing of breast-cancer cells to congenial environment
      of specific organs. Microenvironmental stimuli activating c-Src might influence
      Ets1 binding to CXCR4 promoter and consequent transactivation, as well as CXCR4
      post-translational regulatory mechanisms such as phosphorylation. Enhancement of
      Ets1 activity and CXCR4 induction by c-Src overexpression were prevented by
      histone deacetylase (HDAC) blockade. In contrast, HDAC inhibition with
      trichostatin A increased cytosolic phosphorylated CXCR4 expression in MDA-MB231
      cells, but Ets1 involvement was practically unneeded. c-Src might be suggested as
      a bio-marker predicting metastasis sensitivity patterns to HDAC inhibitors.
      Rationally designed and individualized therapy may become possible as more is
      learned about the target molecules of HDAC's inhibitory agents and their roles,
      as undertaken for CXCR4 that is likely to be crucial for homing, angiogenesis and
      survival in a c-Src-dependent manner in bone-metastatic mammary cells.

PMID- 21741416
TI  - Detection of volatile compounds produced by microbial growth in urine by selected
      ion flow tube mass spectrometry (SIFT-MS).
AB  - Selected ion flow tube-mass spectrometry has been used to measure the volatile
      compounds occurring in the headspace of urine samples inoculated with common
      urinary tract infection (UTI)-causing microbes Escherichia coli, Proteus
      vulgaris, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus
      epidermidis, Klebsiella pneumoniae, Enterococcus faecalis, or Candida albicans.
      This technique has the potential to offer rapid and simple diagnosis of the
      causative agent of UTIs.

PMID- 21741417
TI  - Direct ethanol production from hemicellulosic materials of rice straw by use of
      an engineered yeast strain codisplaying three types of hemicellulolytic enzymes
      on the surface of xylose-utilizing Saccharomyces cerevisiae cells.
AB  - The cost of the lignocellulose-hydrolyzing enzymes used in the saccharification
      process of ethanol production from biomass accounts for a relatively high
      proportion of total processing costs. Cell surface engineering technology has
      facilitated a reduction in these costs by integrating saccharification and
      fermentation processes into a recombinant microbe strain expressing heterologous
      enzymes on the cell surface. We constructed a recombinant Saccharomyces
      cerevisiae that not only hydrolyzed hemicelluloses by codisplaying endoxylanase
      from Trichoderma reesei, beta-xylosidase from Aspergillus oryzae, and beta
      glucosidase from Aspergillus aculeatus but that also assimilated xylose through
      the expression of xylose reductase and xylitol dehydrogenase from Pichia stipitis
      and xylulokinase from S. cerevisiae. The recombinant strain successfully produced
      ethanol from rice straw hydrolysate consisting of hemicellulosic material
      containing xylan, xylooligosaccharides, and cellooligosaccharides without
      requiring the addition of sugar-hydrolyzing enzymes or detoxication. The ethanol
      titer of the strain was 8.2g/l after 72h fermentation, which was approximately
      2.5-fold higher than that of the control strain. The yield (grams of ethanol per
      gram of total sugars in rice straw hydrolysate consumed) was 0.41g/g, which
      corresponded to 82% of the theoretical yield. The cell surface-engineered strain
      was thus highly effective for consolidating the process of ethanol production
      from hemicellulosic materials.

PMID- 21741418
TI  - No increase in the expression of key unfolded protein response genes in HCV
      genotype 3 patients with severe steatosis.
AB  - Although hepatic steatosis is common in patients infected with HCV, the
      mechanisms leading to cellular triglyceride retention are obscure. A role for the
      Unfolded Protein Response (UPR) has been postulated, either through its
      activation or dysfunction. In this study we set out to investigate the expression
      of key UPR genes in HCV genotype 3 patients with moderate to severe steatosis.
      RNA was extracted from liver obtained by percutaneous biopsy and key genes from
      the UPR were semi quantified using real-time PCR. We compared values in patients
      with minimal steatosis to those with high steatosis. Patients with high steatosis
      were younger (44.6 +/- 2.4 vs. 37.4 +/- 2.1, p<0.05) and had higher hepatic viral
      RNA loads (1.00 +/- 0.21 vs. 3.98 +/- 0.22, p<0.05). We found no significant
      difference in the expression of UPR genes, except for a small increase in EDEM1
      in the high steatosis group (1.00 +/- 0.13 vs. 1.38 +/- 0.09, p<0.05). In
      conclusion, despite a four-fold greater concentration of HCV RNA in tissue with a
      high level of steatosis, we found no change in the expression of key UPR related
      genes, except for a only a modest up-regulation of EDEM1. Our data does not
      support a sustained change in expression of UPR genes in the steatogenesis of
      HCVGT3 infected human liver.

PMID- 21741419
TI  - High molecular variability of sugarcane bacilliform viruses in Guadeloupe
      implying the existence of at least three new species.
AB  - Thirty-five unique partial sugarcane bacilliform virus (SCBV) sequences extending
      over 529 bp were identified in sugarcane samples from Guadeloupe diagnosed by
      Immunocapture-PCR (IC-PCR) using specific badnavirus primers. Phylogenetic
      analysis of these sequences along with the two known genome sequences of
      Sugarcane bacilliform Mor virus (SCBMV) and Sugarcane bacilliform IM virus
      (SCBIMV) revealed high molecular variability in the SCBV genome. Seven
      phylogenetic groups, named A to G, were characterized: virus isolates from groups
      A-B, C and D are proposed to be members of three additional SCBV species. The two
      (7446 and 7444 bp) and one (7317 bp) complete sequences of SCBV isolates from
      groups A and D, respectively, likely represented the genome of two new species.
      Phylogenetic analysis of the complete genome and RT/RNase H sequences confirmed
      the polyphyletic structure of SCBV isolates and the absence of a clear separation
      between SCBV and Banana streak virus (BSV) isolates within badnavirus group 1.
      These results showed that reconsideration of taxonomy and classification of SCBV
      and BSV are necessary.

PMID- 21741420
TI  - Isolation and characterization of Neosartorya fischeri antifungal protein (NFAP).
AB  - A novel 6.6 kDa antifungal peptide (NFAP) from the culture supernatant of the
      mold, Neosartorya fischeri (anamorf: Aspergillus fischerianus), and its encoding
      gene were isolated in this study. NFAP is a small, basic and cysteine-rich
      protein consisting of 57 amino acid residues. It shows 37.9-50% homology to
      similar proteins described in literature from Aspergillus clavatus, Aspergillus
      giganteus, Aspergillus niger, and Penicillium chrysogenum. The in silico presumed
      tertiary structure of NFAP, e.g. the presence of five antiparallel beta-sheet
      connected with filaments, and stabilized by three disulfide bridges, is very
      similar to those of the defensin-like molecules. NFAP exhibited growth inhibitory
      action against filamentous fungi in a dose-dependent manner, and maintained high
      antifungal activity within broad pH and temperature ranges. Furthermore, it
      exhibited relevant resistance to proteolysis. All these characteristics make NFAP
      a promising candidate for further in vitro and in vivo investigations aiming at
      the development of new antifungal compounds.

PMID- 21741421
TI  - A "silent" nucleotide substitution in exon 4 is responsible for the "alternative
      expression" of HLA-A*01:01:38L through aberrant splicing.
AB  - A Welsh Bone Marrow Donor Registry donor was serologically typed, using both
      alloantisera and monoclonal antibodies, as human leukocyte antigen (HLA)-A2, A-,
      but typed by polymerase chain reaction sequence-specific priming as HLA-A*01,
      A*02. Full gene sequencing of the A*01 separated allele indicated an apparently
      normal A*01:01:01:01 apart from a silent change at nucleotide 705 in exon 4,
      codon 211 (alanine: normally GCG but GCA in this donor). Sequence analysis of the
      amplified A*01 allele in cDNA synthesized from RNA indicated that exons 1, 2, 3,
      and 5 had typical A*01:01 sequences. However, exon 4 was truncated in this allele
      (87 nucleotides shorter), beginning just after the single nucleotide polymorphism
      (SNP) identified in genomic DNA sequencing. The nucleotide sequence up to, and 1
      nucleotide after, the SNP is homologous with the 3' end of human leukocyte
      antigen (HLA)-A intron 3 and thus resembles a splice site. However, a small
      amount of "normal" HLA-A1 was detected on the surface of cells from an Epstein
      Barr virus transformed B-cell line (BCL), but not on peripheral blood mononuclear
      cells, by flow cytometry. Additionally, a trace amount of "normal sized" A*01 was
      amplified from cDNA. We suggest that in this A*01 variant allele (A*01:01:38L)
      intron 3 is largely spliced out with a part of exon 4; exon 4 is still in-frame
      but the protein is smaller than the wild type. This is likely to affect folding
      and assembly of the "wild type" mature protein on the cell surface, thus
      explaining the apparent null phenotype when assayed by conventional serology.
      However, a small amount of A1 protein is made from correctly spliced A*01 mRNA
      and is detectable on BCLs using flow cytometry.

PMID- 21741422
TI  - Simplified sequence-specific oligonucleotide-based polymerase chain reaction
      protocol to characterize human major histocompatibility complex A*02 and A*24
      specificities.
AB  - Major histocompatibility complex (MHC) multimer technology is used in studies of
      high scientific and clinical interest for the identification, analysis,
      purification, and adoptive transfer of virus-specific T cells. MHC peptide
      multimers are usually specific for MHC A*02 or A*24 specificities because both
      specificities exhibit a high worldwide frequency. However, commercially available
      typing methods perform complete typing instead of browsing for these prevailing
      specificities. In this study we demonstrate an easy and accessible polymerase
      chain reaction-based method to accurately identify A*02 and A*24 samples in a
      cost-effective way.

PMID- 21741423
TI  - Induction of CD56+ T cells after prolonged activation of T cells in vitro: a
      possible mechanism for CD4+ T-cell depletion in acquired immune deficiency
      syndrome patients.
AB  - The pathogenic mechanisms responsible for depletion of CD4(+) T cells in aquired
      immune deficiency syndrome (AIDS) are not fully understood. Systemic immune
      activation mediated by persistent infection of human immunodeficiency virus (HIV)
      seems to be one of the predictors of disease progression. We predicted that
      certain lymphocytes responsible for CD4(+) T-cell depletion could be induced in
      patients during prolonged activation of lymphocytes. Therefore, we have
      established an in vitro long-term culture system for peripheral blood mononuclear
      cells with PHA-P stimulation and Herpesvirus saimiri infection, and examined what
      types of cells having strong cytotoxic activity to be emerged under the activated
      conditions. We observed that percentage of CD56(+) T cells was gradually
      increased in cultures from 30 days after stimulation and exhibited a cytotoxic
      activity against both autologous and allogeneic targets. Interestingly, HIV-1
      infection enhanced the susceptibility of CD4(+) T cells to their cytotoxic
      effectors, and CD4(+) T cells from HIV-1-infected individuals showed decreased
      survival rate in the presence of autologous CD56(+) T cells. These findings
      raised the possibility that induction of autoreactive CD56(+) T cells in
      consequence of immune activation might be contributed to the depletion of CD4(+)
      T cells in HIV-1-infected patients.

PMID- 21741425
TI  - Curcumin inhibits glutamate release in nerve terminals from rat prefrontal
      cortex: possible relevance to its antidepressant mechanism.
AB  - There is abundant evidence suggesting the relevance of glutamate to depression
      and antidepressant mechanisms. Curcumin, a major active compound of Curcuma
      longa, has been reported to have the biological function of antidepressant. The
      aim of the present study was to investigate the effect of curcumin on endogenous
      glutamate release in nerve terminals of rat prefrontal cortex and the underlying
      mechanisms. The results showed that curcumin inhibited the release of glutamate
      that was evoked by exposing synaptosomes to the K(+) channel blocker 4
      aminopyridine (4-AP). This phenomenon was blocked by the chelating the
      extracellular Ca(2+) ions, and by the vesicular transporter inhibitor bafilomycin
      A1, but was insensitive to the glutamate transporter inhibitor DL-threo-beta
      benzyl-oxyaspartate (DL-TBOA). Further experiments demonstrated that curcumin
      decreased depolarization-induced increase in [Ca(2+)](C), whereas it did not
      alter the resting membrane potential or 4-AP-mediated depolarization.
      Furthermore, the inhibitory effect of curcumin on evoked glutamate release was
      prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but
      not by blocking intracellular Ca(2+) release or Na(+)/Ca(2+) exchange. These
      results suggest that curcumin inhibits evoked glutamate release from rat
      prefrontocortical synaptosomes by the suppression of presynaptic Ca(v)2.2 and
      Ca(v)2.1 channels. Additionally, we also found that the inhibitory effect of
      curcumin on 4-AP-evoked glutamate release was completely abolished by the
      clinically effective antidepressant fluoxetine. This suggests that curcumin and
      fluoxetine use a common intracellular mechanism to inhibit glutamate release from
      rat prefrontal cortex nerve terminals.

PMID- 21741424
TI  - Immunotherapy in prostate cancer: emerging strategies against a formidable foe.
AB  - Recent clinical trials have shown therapeutic vaccines to be promising treatment
      modalities against prostate cancer. Unlike preventive vaccines that teach the
      immune system to fight off specific microorganisms, therapeutic vaccines
      stimulate the immune system to recognize and attack certain cancer-associated
      proteins. Additional strategies are being investigated that combine vaccines and
      standard therapeutics, including radiation, chemotherapy, targeted therapies, and
      hormonal therapy, to optimize the vaccines' effects. Recent vaccine late-phase
      clinical trials have reported evidence of clinical benefit while maintaining
      excellent quality of life. One such vaccine, sipuleucel-T, was recently FDA
      approved for the treatment of metastatic prostate cancer. Another vaccine, PSA
      TRICOM, is also showing promise in completed and ongoing randomized multicenter
      clinical trials in both early- and late-stage prostate cancer. Clinical results
      available to date indicate that immune-based therapies could play a significant
      role in the treatment of prostate and other malignancies.

PMID- 21741426
TI  - Myricetin affords protection against peroxynitrite-mediated DNA damage and
      hydroxyl radical formation.
AB  - Peroxynitrite has been extensively implicated in the pathogenesis of various
      forms of neurodegenerative disorders via its cytotoxic effects, this study was
      undertaken to investigate whether the neuroprotective effect of myricetin is
      associated with inhibition of peroxynitrite-mediated DNA damage, a critical event
      leading to peroxynitrite elicited cytotoxicity. We observed that peroxynitrite
      can cause DNA damage in phiX-174 plasmid DNA and rat primary astrocytes. The
      presence of myricetin at physiological concentration was found to significantly
      inhibit DNA strand breakage induced by both peroxynitrite and its generator 3
      morpholinosydnonimine (SIN-1). Moreover, the consumption of oxygen caused by SIN
      1 was found to be decreased in the presence of myricetin, indicating that
      myricetin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy
      demonstrated that the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from
      peroxynitrite, and that myricetin inhibited the adduct signal in a concentration
      dependent manner. Taken together, these results demonstrate for the first time
      that myricetin can inhibit peroxynitrite-mediated DNA damage and hydroxyl radical
      formation.

PMID- 21741427
TI  - A novel non-aromatic B-ring flavonoid: isolation, structure elucidation and its
      induction of apoptosis in human colon HT-29 tumor cell via the reactive oxygen
      species-mitochondrial dysfunction and MAPK activation.
AB  - The aim of the present study was to elucidate the chemical structure of a novel
      non-aromatic B-ring flavonoid (DHEC) isolated from Macrothelypteris viridifrons
      and to evaluate its putative molecular mechanism of action on induction of
      apoptosis in human colon HT-29 cancer cell. On the basis of MS, UV, IR, 1D and 2D
      NMR data, DHEC was identified as 2-(cis-1, 2-dihydroxy-4-oxo-cyclohex-5-enyl)-5
      hydroxy-7-ethoxy-chromone. In addition, the cytotoxicity of DHEC and its effect
      on induction of apoptosis were confirmed by several assays. After treatment of HT
      29 cell with DHEC, we observed the accumulation of intracellular reactive oxygen
      species, the loss of mitochondrial membrane potential, the alteration of
      expression of the Bcl-2 family members, the releasing of cytochrome c, the
      cleavage of poly (ADP-ribose) polymerase (PARP), and the activation of caspase-3,
      -8, and -9. Further analysis showed that the mitogen-activated protein kinase
      (MAPK) related proteins were stimulated by treatment with DHEC. These results
      suggest that DHEC exhibits potential anti-cancer activity in HT-29 cell through
      induction of apoptosis, which may highly be associated with reactive oxygen
      species-mitochondrial dysfunction as well as activation of MAPK signaling
      pathway.

PMID- 21741428
TI  - Prevention of toothbrushing abrasion of acid-softened enamel by CO(2) laser
      irradiation.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effect of CO(2) laser
      irradiation (10.6MUm) at 0.3J/cm(2) (0.5MUs; 226Hz) on the resistance of softened
      enamel to toothbrushing abrasion, in vitro. METHODS: Sixty human enamel samples
      were obtained, polished with silicon carbide papers and randomly divided into
      five groups (n=12), receiving 5 different surface treatments: laser irradiation
      (L), fluoride (AmF/NaF gel) application (F), laser prior to fluoride (LF),
      fluoride prior to laser (FL), non-treated control (C). After surface treatment
      they were submitted to a 25-day erosive-abrasive cycle in 100ml sprite light
      (90s) and brushed twice daily with an electric toothbrush. Between the
      demineralization periods samples were immersed in supersaturated mineral
      solution. At the end of the experiments enamel surface loss was determined using
      a contact profilometer and morphological analysis was performed using scanning
      electron microscopy (SEM). For SEM analysis of demineralization pattern, cross
      sectional cuts of cycled samples were prepared. The data were statistically
      analysed by one-way ANOVA model with subsequent pairwise comparison of
      treatments. RESULTS: Abrasive surface loss was significantly lower in all laser
      groups compared to both control and fluoride groups (p<0.0001 in all cases).
      Amongst the laser groups no significant difference was observed. Softened enamel
      layer underneath lesions was less pronounced in laser-irradiated samples.
      CONCLUSION: Irradiation of dental enamel with a CO(2) laser at 0.3J/cm(2) (5MUs,
      226Hz) either alone or in combination with amine fluoride gel significantly
      decreases toothbrushing abrasion of softened-enamel, in vitro.

PMID- 21741429
TI  - Understanding the allosteric trigger for the fructose-1,6-bisphosphate regulation
      of the ADP-glucose pyrophosphorylase from Escherichia coli.
AB  - ADP-glucose pyrophosphorylase is the enzyme responsible for the regulation of
      glycogen synthesis in bacteria. The enzyme N-terminal domain has a Rossmann-like
      fold with three neighbor loops facing the substrate ATP. In the Escherichia coli
      enzyme, one of those loops also faces the regulatory site containing Lys(39), a
      residue involved in binding of the allosteric activator fructose-1,6-bisphosphate
      and its analog pyridoxal-phosphate. The other two loops contain Trp(113) and
      Gln(74), respectively, which are highly conserved among all the ADP-glucose
      pyrophosphorylases. Molecular modeling of the E. coli enzyme showed that binding
      of ATP correlates with conformational changes of the latter two loops, going from
      an open to a closed (substrate-bound) form. Alanine mutants of Trp(113) or
      Gln(74) did not change apparent affinities for the substrates, but they became
      insensitive to activation by fructose-1,6-bisphosphate. By capillary
      electrophoresis we found that the mutant enzymes still bind fructose-1,6
      bisphosphate, with similar affinity as the wild type enzyme. Since the mutations
      did not alter binding of the activator, they must have disrupted the
      communication between the regulatory and the substrate sites. This agrees with a
      regulatory mechanism where the interaction with the allosteric activator triggers
      conformational changes at the level of loops containing residues Trp(113) and
      Gln(74).

PMID- 21741430
TI  - Attenuated mitochondrial NADP+-dependent isocitrate dehydrogenase activity
      enhances EGCG-induced apoptosis.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), a well-known chemopreventive factor,
      induces cancer cells undergoing apoptosis. Over the last several years, we have
      shown that the mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm)
      functions as an antioxidant and anti-apoptotic protein by supplying NADPH to
      antioxidant systems. Here, we show that EGCG induced the inactivation of IDPm as
      a purified enzyme and in cultured cancer cells in a dose- and time-dependent
      manner. Loss of enzyme activity was associated with the depletion of the thiol
      groups in protein. In addition, transfection of HeLa cells with an IDPm small
      interfering RNA (siRNA) markedly attenuated the activity of IDPm and
      substantially enhanced EGCG-induced apoptosis as indicated by the morphological
      evidence of apoptosis, DNA fragmentation, and the modulation of mitochondrial
      function and apoptotic marker proteins. Taken together, our results suggest that
      the suppression of IDPm activity resulted in the disruption of cellular redox
      balance and subsequently exacerbates EGCG-induced apoptotic cell death in HeLa
      cells. These results might have implications for developing an effective
      combination modality in cancer treatment.

PMID- 21741431
TI  - Automated external defibrillators and in-hospital cardiac arrest: patient
      survival and device performance at an Australian teaching hospital.
AB  - AIMS: To evaluate the effect of automated external defibrillators (AEDs) on
      patient survival and to describe the performance of AEDs after in-hospital
      cardiac arrest. METHODS: Prospectively collected data were analysed for cardiac
      arrests in the general patient care areas of a teaching hospital during the 3
      years before and the 3 years after the deployment of AEDs. The association
      between availability of an AED and survival to hospital discharge was assessed
      using multivariate logistic regression. AED performance during automated
      management of the initial rhythms was assessed using information captured by the
      AEDs. RESULTS: There were 84 cardiac arrests in the AED period and 82 in the pre
      AED period. Patient and event characteristics were similar in each period. The
      initial rhythm was shockable in 16% of cases. Return of spontaneous circulation
      was higher in the AED period (54% vs. 35%, P=0.02) but the proportion of hospital
      survivors in each period was similar (22% vs. 19%, P=0.56). The adjusted odds
      ratio for hospital survival when an AED was available was 1.22 (95% CI 0.53-2.84,
      P=0.64). An AED was applied in 77/84 (92%) possible cases. Median interruption to
      chest compressions was 12s (inter-quartile range 12-13). An automated shock was
      delivered in 8/13 (62%) possible cases. CONCLUSIONS: Availability of AEDs was not
      independently associated with hospital survival. Shockable presenting rhythms
      were not common and, in keeping with the manufacturer's specifications, the AEDs
      did not shock all potentially shockable rhythms. The hands-off time associated
      with automated rhythm management was considerable.

PMID- 21741432
TI  - Practice variability among the EMS systems participating in Cardiac Arrest
      Registry to Enhance Survival (CARES).
AB  - STUDY OBJECTIVE: To describe the demographic, organizational and provider
      characteristics of the Emergency Medical Services (EMS) agencies participating in
      the Cardiac Arrest Registry to Enhance Survival (CARES). METHODS: A web based
      survey instrument was developed by the CARES investigators and distributed to the
      EMS agencies participating in CARES in 2008. Survey questions addressed three
      domains related to prehospital care: (1) descriptors of the participating EMS
      agencies, (2) methods of clinical care and clinical protocols used by EMS
      agencies to deliver out-of-hospital cardiac arrest care and (3) use of
      resuscitation techniques by EMS agencies. Survey responses were collated and
      analyzed using descriptive statistics. RESULTS: Surveys were received from 21/25
      (84%) sites. The EMS agency characteristics including the response areas served
      by the agencies, organizational structure, medical direction status and
      deployment status are described. All respondents were non-volunteer agencies with
      a large number of them being fire-based (43%). Significant variability among the
      communities was observed with respect to their medical direction status and
      deployment status. We also observed differences in the management of OHCA among
      the participating agencies which included implementation of ACLS guideline
      updates, presence of termination of resuscitation protocol and destination
      policies for OHCA subjects. Similar variations between agencies were also
      observed in the use of resuscitation techniques. CONCLUSIONS: Differences were
      observed between the EMS agencies participating in CARES. The clinical impact of
      these observed differences in agency and provider characteristics on OHCA
      outcomes deserves study.

PMID- 21741433
TI  - Prefrontal asymmetry predicts affect, but not beliefs about affect.
AB  - Self-reported emotional feelings are easily biased by situational or identity
      related beliefs. Such biases vary as a function of memory. Recent memories draw
      more on veridical felt affective experience whereas distant memories draw more on
      situational or identity-related biases. For this study, frontal EEG asymmetry was
      used to predict feeling- versus belief-based self-reports of freshmen year
      homesickness in college freshmen and sophomores. Relatively greater right frontal
      EEG asymmetry predicted greater feeling-based, experiential reports of freshman
      year homesickness, whereas no associations were found between frontal EEG
      asymmetry and belief-based, retrospective reports of freshman year homesickness.
      These results support the status of frontal EEG asymmetry as a measure of
      affective vulnerability and suggest that links between frontal EEG asymmetry and
      self-reported affect are detectable to the extent that self-reports capture
      current emotional feelings and not situational or identity-related beliefs about
      what one ought to have felt.

PMID- 21741434
TI  - Age effects on retroactive interference during working memory maintenance.
AB  - The present study uses magnetoencephalography (MEG) to examine brain magnetic
      patterns in young and older adults who perform an interference-based working
      memory (WM) task with two experimental conditions; interrupting and distracting.
      Behaviourally, both types of retroactive interference significantly impair WM
      accuracy at recognition more in older adults than in young adults with the latter
      exhibiting greater disruptions by interruptors. MEG results revealed the presence
      of differential age-related and interference-related neural patterns.
      Specifically, time-modulated activations in posterior-frontal regions were
      increased in young compared to older adults characterising each condition.
      Additionally, young adults exhibited greater posterior-frontal activations for
      the interrupting compared to the distracting condition. These results suggest
      that age-related deficits in inhibitory mechanisms that increase vulnerability to
      interference are associated with under-recruitments in posterior-frontal regions.
      On the other hand, the absence of differential interference-related neural
      recruitments reflects that both types of interference affect WM equally in the
      elderly.

PMID- 21741436
TI  - Dietary flavones and flavonones display differential effects on aromatase (CYP19)
      transcription in the breast cancer cells MCF-7.
AB  - Aromatase or cytochrome P450 (CYP19) enzyme catalyzes the rate-determining
      reaction in estrogen synthesis. Inhibiting aromatase is a major strategy in
      treating breast cancer patients. However, suppression on the transcriptional
      activity may be equally important in controlling aromatase. Dietary flavones and
      flavonones have been previously demonstrated to be the most potent aromatase
      inhibitory flavonoids. In the present study we examined their effects on the
      transcription regulation of CYP19 in MCF-7 cells. Real-time PCR results indicated
      that luteolin suppressed CYP19 mRNA expression while hesperetin increased it.
      Reporter gene assays were employed to look into the transactivity of CYP19 driven
      by promoters I.3 and II, and the result was consistent with the observation in
      mRNA expression. Further investigation using truncation reporter gene and
      electrophoretic mobility shift assays suggested that luteolin and hesperetin
      differentially influenced AP-1- and C/EBP-binding on the CYP19 promoter. Western
      blot analysis indicated that signaling transduction pathways involving JNK and
      ERK could be the underlying mechanisms for their actions. The present study
      showed that dietary flavones and flavonones might differentially regulate
      aromatase transcription in breast cells in addition to the inhibition at the
      enzyme level.

PMID- 21741435
TI  - Biological mechanisms underlying the relationship between stress and smoking:
      state of the science and directions for future work.
AB  - Theories of addiction implicate stress as a crucial mechanism underlying
      initiation, maintenance, and relapse to cigarette smoking. Examinations of the
      biological stress systems, including functioning of the hypothalamic-pituitary
      adrenal (HPA) axis and the autonomic nervous system (ANS), have provided
      additional insights into the relationship between stress and smoking. To date,
      convergent data suggests that chronic cigarette smoking is associated with
      alterations in HPA and ANS functioning; however, less is known about the role of
      HPA and ANS functioning in smoking initiation and relapse following cessation. In
      order to organize existing findings and stimulate future research, the current
      paper summarizes the available literature on the roles of HPA axis and ANS
      functioning in the relationship between stress and cigarette smoking, highlights
      limitations within the existing literature, and suggests directions for future
      research to address unanswered questions in the extant literature on the
      biological mechanisms underlying the relationship between stress and smoking.

PMID- 21741437
TI  - Diagnostic applications for inhibin and activins.
AB  - Inhibin and activins play major roles as paracrine and autocrine signaling
      molecules in reproduction and development where the main emphasis has been placed
      in developing potential diagnostic applications. While a role for activin assays
      in diagnostics has so far been unfounded, ELISAs specific for the biologically
      active inhibin A and B dimers, and for free inhibin alpha subunits, alone or in
      combination have found some specific diagnostic applications. Addition of inhibin
      A to the triple test for Down syndrome in the second trimester of pregnancy,
      measurement of total inhibin as a marker of certain forms of ovarian cancer in
      specific circumstances, and inhibin B for male fertility are useful diagnostics.
      A review of the evidence so far suggests that other applications for inhibin and
      activin assays have yet to be confirmed, or translated into reliable tools for
      clinical practice.

PMID- 21741438
TI  - The developmental biology of the GnRH neurons.

PMID- 21741439
TI  - Valproic acid inhibits neurosphere formation by adult subventricular cells by a
      lithium-sensitive mechanism.
AB  - The mood stabilizer valproic acid (VPA) decreases neural progenitor proliferation
      and promotes neurogenesis in the adult hippocampus. However, the effects of VPA
      on progenitor cells in the adult subventricular zone (SVZ) are not as well
      characterized. Here we report VPA blocks neurosphere formation and inhibits DNA
      synthesis in cultured NSCs from the SVZ of adult mice. Inhibition of DNA
      synthesis is associated with the up-regulation of the differentiation
      transcription factors Egr1 and Neurod1 and down-regulation of transcription
      factors associated with "stemness". Co-treatment of VPA with the mood stabilizer
      lithium antagonizes the anti-proliferative effects of VPA on adult NSCs and
      abolishes VPA activation of Egr1. Co-treatment of VPA with the MEK1/2 inhibitor
      PD980589 similarly abolishes Egr1 activation consistent with VPA activation and
      lithium antagonism of MEK-ERK signaling in adult NSCs. However, Western blot
      reveals VPA significantly suppresses ERK2 phosphorylation in adult NSCs grown in
      proliferating culture conditions and that lithium co-treatment does not attenuate
      this effect. Combined the data indicate VPA inhibition of adult NSC proliferation
      and activation of Egr1 by VPA, along with the antagonism of these effects by
      lithium, are the effects of cumulative changes in multiple signaling pathways and
      are not attributable to a common kinase target.

PMID- 21741440
TI  - Saccade adaptation improves in response to a gradually introduced stimulus
      perturbation.
AB  - A major goal in the study of motor learning is to improve the extent to which
      subjects adapt their movements in response to errors. Recent attention has
      focused on the gradual-adaptation paradigm, in which an adaptive stimulus is
      introduced incrementally, rather than all at once as in conventional adaptation
      paradigms. However, there is disagreement - even among studies involving the same
      sensorimotor-learning task - as to the robustness of this approach. In
      particular, although all studies confirm that retention of learning is improved,
      not all agree that exposure to a gradual-adaptation paradigm can improve the
      extent of adaptation that takes place. Also, the paradigm has not previously been
      studied with saccadic eye movements, which are unique in that they typically lack
      online error feedback during each movement. To determine the effectiveness of
      gradual adaptation in this system, we compared saccadic adaptation performed with
      gradual and conventional adaptation paradigms. We find evidence consistent with
      more robust adaptation - in the sense of greater extent of adaptation as well as
      greater retention of learning (larger aftereffects) - in response to a gradual
      adaptation stimulus. The results suggest the need to develop alternative models
      of motor learning, as current error-based modeling efforts are unable to account
      for the increased extent of adaptation when subjects are only exposed to the full
      adaptive stimulus for a brief time.

PMID- 21741441
TI  - Increased annexin-V and decreased TNF-alpha serum levels in chronic-medicated
      patients with schizophrenia.
AB  - Schizophrenia (SZ) is a chronic severe mental disorder. Increased inflammatory
      processes have been shown in acute and chronic SZ. Apoptotic processes may alter
      the neuronal network and are involved in the pathogenesis of several
      neurodegenerative diseases, such as SZ. Annexin-V seems to have a role on
      inhibition of pro-inflammatory activities during apoptosis. Tumor necrosis factor
      (TNF-alpha) is a cytokine involved in systemic inflammation and is a member of a
      group of cytokines which stimulate acute phase reactions. A chronic immune
      activation in SZ has been shown. The aim of this study was to compare annexin-V
      and TNF-alpha serum levels in chronic medicated patients with SZ and healthy
      controls. Thirty-eight outpatients from the HCPA Schizophrenia Program and 38
      healthy controls were enrolled to this study protocol. Annexin-V and TNF-alpha
      serum levels were measured with ELISA. Serum annexin-V levels were significantly
      higher in patients with SZ than in controls (p<0.001) and TNF-alpha significantly
      lower (p<0.001). The present result of increased annexin-V and decreased serum
      levels of TNF-alpha compared to controls may be a result of the stabilization
      phase of psychosis and a reduction in metabolic brain aggression. In this complex
      picture, increased levels of annexin-V and decreased levels of TNF-alpha in our
      sample would be explained by illness stability and chronic treatment. Our
      findings support the hypothesis of a state dependant process of inflammation in
      SZ. Further prospective studies to clarify the findings described in this paper
      are needed.

PMID- 21741442
TI  - A transgenic mouse model for Alzheimer's disease has impaired synaptic gain but
      normal synaptic dynamics.
AB  - The chronic accumulation of amyloid beta (Abeta) peptides is thought to underlie
      much of the pathology of Alzheimer's disease (AD), and transgenic mice
      overexpressing Abeta show both behavioral defects and impairments in hippocampal
      synaptic transmission. In the present study, we examined excitatory transmission
      at the Schaffer collateral synapse in acute hippocampal slices from APP(Swe)/PS
      1(A246E) transgenic mice to determine whether the synaptic impairment in these
      mice is due to a reduction in the activity-independent synaptic gain, or to a
      change in the activity-dependent synaptic dynamics. We observed a strong
      reduction in synaptic transmission in slices from APP(Swe)/PS-1(A246E) mice
      compared to those from their wildtype littermates. However, there was no
      resolvable change in the synaptic dynamics observed in response to either simple
      or complex stimulus trains. We conclude that the chronic accumulation of Abeta
      impairs synaptic transmission through a reduction in the synaptic gain, while
      preserving the synaptic dynamics.

PMID- 21741443
TI  - Cortical processing of tactile direction discrimination based on spatiotemporal
      cues in man.
AB  - Tactile direction discrimination (TDD), the ability to determine the direction of
      an object's movement across the skin, is used clinically to detect and quantify
      tactile dysfunction. We have previously identified a cortical network for TDD
      based on skin stretch information that includes the second somatosensory,
      anterior insular and dorsolateral prefrontal cortices. In the present study we
      investigated cortical processing of TDD based on spatiotemporal cues. Sixteen
      healthy subjects (8 females; mean age, 25.5 years; range, 23-32 years) were
      stimulated with a low-friction, spatiotemporal rolling wheel on the right thigh
      during functional magnetic resonance imaging (fMRI). The subjects were instructed
      to indicate the distal or proximal rolling direction of the stimulus. The fMRI
      contrast between rolling wheel stimulation and rest showed activations in several
      areas which included the left (contralateral) primary somatosensory, bilateral
      second somatosensory, bilateral anterior insular, and bilateral dorsolateral
      prefrontal cortices. We conclude that, spatiotemporal TDD is processed in a
      largely similar distributed cortical network as skin stretch TDD. Further,
      spatiotemporal TDD activated primary somatosensory cortex whereas a role for this
      area in processing of skin stretch TDD has not been demonstrated.

PMID- 21741444
TI  - Genetic studies of the protein kinase AKT1 in Parkinson's disease.
AB  - The protein kinase AKT1 belongs to the Akt family and is a potent mediator of
      cell growth and survival and fully activated when phosphorylated. The AKT family
      has been found to be phosphorylated to a lesser extent in the dopaminergic cells
      of Parkinson's disease patients compared to control individuals, which might
      influence cell survival. Several publications support the implication of AKT1 in
      disorders of the dopaminergic system including bipolar disease and schizophrenia.
      In 2008 an association study performed in a Greek Parkinson's disease case
      control material reported the identification of a protective AKT1 haplotype.
      Based on their work we have performed a replication study in a Swedish
      Parkinson's disease cohort. We genotyped the four single nucleotide polymorphims
      (SNPs): rs2494743, rs2498788, rs2494746 and rs1130214 in a case-control material
      consisting of 243 Parkinson patients and 315 controls. We did not find any
      associations with Parkinson's disease for either the individual SNPs or any of
      the haplotypes. In contrast to previously published results, our data do not
      support the hypothesis of genetic variants in AKT1 confering protection against
      Parkinson's disease.

PMID- 21741445
TI  - Differential gene expression of neonatal and adult DRG neurons correlates with
      the differential sensitization of TRPV1 responses to nerve growth factor.
AB  - Cultures of neonatal and adult dorsal root ganglion (DRG) neurons are commonly
      used in in vitro models to study the ion channels and signaling events associated
      with peripheral sensation under various conditions. Differential responsiveness
      between neonatal and adult DRG neurons to physiological or pathological stimuli
      suggests potential differences in their gene expression profiles. We performed a
      microarray analysis of cultured adult and neonatal rat DRG neurons, which
      revealed distinct gene expression profiles especially of ion channels and
      signaling molecules at the genomic level. For example, Ca(2+)-stimulated adenylyl
      cyclase (AC) isoforms AC3 and AC8, PKCdelta and CaMKIIalpha, the voltage-gated
      sodium channel beta1 and beta4, and potassium channels K(v)1.1, K(v)3.2, K(v)4.1,
      K(v)9.1, K(v)9.3, K(ir)3.4, K(ir)7.1, K(2P)1.1/TWIK-1 had significantly higher
      mRNA expression in adult rat DRG neurons, while Ca(2+)-inhibited AC5 and AC6,
      sodium channel Na(v)1.3 alpha subunit, potassium channels K(ir)6.1,
      K(2P)10.1/TREK-2, calcium channel Ca(v)2.2 alpha1 subunit, and its auxiliary
      subunits beta1 and beta3 were conversely down regulated in adult neurons.
      Importantly, higher adult neuron expression of ERK1/2, PI3K/P110alpha, but not of
      TRPV1 and TrkA, was found and confirmed by PCR and western blot. These latter
      findings are consistent with the key role of ERK and PI3K signaling in
      sensitization of TRPV1 by NGF and may explain our previously published
      observation that adult, but not neonatal, rat DRG neurons are sensitized by NGF.

PMID- 21741446
TI  - Changes in cerebral glucose metabolism in patients with mild-to-moderate
      Alzheimer's disease: a pilot study with the Chinese herbal medicine fuzhisan.
AB  - The aim of this study was to investigate the effects of fuzhisan (FZS, 10mg/day),
      a Chinese herbal medicine, on cerebral glucose metabolism and neuropsychological
      metrics in patients with mild-to-moderate Alzheimer's disease (AD). This was a 12
      week, randomized, double-blind, placebo-controlled pilot study. Twenty-two
      subjects were randomly assigned to groups that received FZS (n=12) or placebo
      (n=10). Positron emission tomography (PET) was used to study the regional
      cerebral metabolic rate of glucose consumption (rCMRglc) at baseline and week 12.
      We evaluated the clinical efficacy of FZS on cognition and behavioral functions
      using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and
      the Neuropsychiatric Index (NPI), respectively. Compared with placebo, FZS
      significantly improved ADAS-Cog scores and NPI scores at week 12. Moreover, FZS
      treatment favorably improved rCMRglc in the bilateral temporal and parietal
      cortices, hippocampus, and posterior cingulate gyrus. These results suggest that
      FZS treatment may have a positive effect on cognition, behavioral functions, and
      rCMRglc in mild-to-moderate AD patients.

PMID- 21741447
TI  - Interaction between two HTR2A polymorphisms and gender is associated with
      treatment response in MDD.
AB  - The 5HT2A receptor gene (HTR2A) polymorphisms rs7997012 and rs6311 have in some
      earlier studies been associated with serotonin selective reuptake inhibitor
      (SSRI) treatment response in major depressive disorder (MDD), but the findings
      are inconsistent. The aim of the present study was to test for an association
      between two HTR2A polymorphisms (rs7997012 and rs6311), their interaction and the
      Montgomery and Asberg Depression Rating Scale (MADRS) score change after ECT or
      SSRI treatment. The total number of patients was 218. All were treated in
      outpatient care. Of these, 119 subjects had treatment-resistant MDD and were
      treated with ECT and 99 were depressive patients treated with SSRI. Treatment
      response was assessed by MADRS. Patients scoring <8 on post-treatment MADRS were
      considered remitters. Neither rs7997012 nor rs6311 HTR2A polymorphism was
      significantly associated with MADRS score change alone, but the interaction
      between them and gender explained 14% of the variance in MADRS score change. The
      finding suggests an association between MADRS score change and interaction of
      HTR2A polymorphisms, rs7997012 and rs6311 and gender.

PMID- 21741448
TI  - RGS9-2 modulates nociceptive behaviour and opioid-mediated synaptic transmission
      in the spinal dorsal horn.
AB  - The regulator of G protein signaling 9-2 (RGS9-2) is a constituent of G protein
      coupled receptor (GPCR) macromolecular complexes with a major role in regulation
      of GPCR activity in the central nervous system. Previous in situ hybridization
      and Western blot studies revealed that RGS9-2 is expressed in the superficial
      dorsal horn of the spinal cord. In the present study, we monitored tail
      withdrawal latencies to noxious thermal stimuli and performed in vitro whole-cell
      patch clamp electrophysiological recordings from neurons in lamina II of the
      spinal dorsal horn to examine the role of RGS9-2 in the dorsal horn of the spinal
      cord in nociceptive behaviours and opiate mediated modulation of synaptic
      transmission. Our findings obtained from RGS9 knockout mice indicate that the
      lack of RGS9-2 protein decreases sensitivity to thermal stimuli and to the
      analgesic actions of morphine in the tail immersion paradigm. This modulatory
      role of RGS9-2 on opiate-mediated responses was further supported by
      electrophysiological studies showing that hyperpolarization of neurons in lamina
      II of the spinal dorsal horn evoked by application of DAMGO ([d-Ala2, N-MePhe4,
      Gly-ol]-enkephalin, a mu opioid receptor agonist) was diminished in RGS9 knockout
      mice. The results indicate that RGS9-2 enhances the effect of morphine and may
      play a crucial role in opiate-mediated analgesic mechanisms at the level of the
      spinal cord.

PMID- 21741449
TI  - The effects of treadmill training on young and mature rats after traumatic
      peripheral nerve lesion.
AB  - The purpose of this study was to investigate the possible effects of a treadmill
      training program on regeneration in young (3-month-old) and mature (13-month-old)
      rats with sciatic nerve crush using functional, electrophysiological, and
      morphometric analyses. When compared to both the young and mature untrained
      injury groups, those groups that underwent a treadmill training showed improved
      sensorimotor function evaluated by narrow beam test (p<0.04 and p<0.001,
      respectively), while muscle action potential amplitude was only greater in the
      young group (p<0.02). The treadmill training program was able to reduce
      myelinated fiber density in the young group (p<0.001), which appeared to increase
      after nerve injury (poly-innervation), but decreased with training, which means
      that the innervation became more functional. The data indicate that treadmill
      training is able to promote functional, electrophysiological and morphological
      recovery in young animals. However, in mature animals, improvement was only seen
      in terms of functional recovery.

PMID- 21741450
TI  - Cortical fMRI activation to opponents' body kinematics in sport-related
      anticipation: expert-novice differences with normal and point-light video.
AB  - Badminton players of varying skill levels viewed normal and point-light video
      clips of opponents striking the shuttle towards the viewer; their task was to
      predict in which quadrant of the court the shuttle would land. In a whole-brain
      fMRI analysis we identified bilateral cortical networks sensitive to the
      anticipation task relative to control stimuli. This network is more extensive and
      localised than previously reported. Voxel clusters responding more strongly in
      experts than novices were associated with all task-sensitive areas, whereas
      voxels responding more strongly in novices were found outside these areas. Task
      sensitive areas for normal and point-light video were very similar, whereas early
      visual areas responded differentially, indicating the primacy of kinematic
      information for sport-related anticipation.

PMID- 21741451
TI  - Effect of daily linear acceleration training on the hypergravity-induced vomiting
      response in house musk shrew (Suncus murinus).
AB  - The effects of repeated linear acceleration training and the antimotion sickness
      drug, promethazine, on hypergravity-induced motion sickness were examined in musk
      shrew (Suncus murinus), which is known to show a vomiting response to motion
      stimulation. Animals were assigned into five groups: vestibular intact, untreated
      animals (Sham), vestibular lesioned (VL) animals, vestibular intact animals with
      promethazine hydrochloride administered as daily drinking water (Prom),
      vestibular intact animals who underwent horizontal linear accelerator motion
      training (Train), and vestibular intact animals treated with both promethazine
      hydrochloride and linear acceleration training (Prom+Train). In Sham animals, the
      number of vomiting episodes was 14+/-2 during 2 G exposure for 10min, and was
      accompanied by intense Fos expression in the medial vestibular nucleus (MVe), the
      nucleus of the solitary tract (NTS), the area postrema (AP), and the
      paraventricular hypothalamic nucleus (PVN). The vomiting response and Fos
      expression were completely abolished in VL animals, indicating that these
      responses are mediated via the vestibular system. Although Train and Prom animals
      experienced a significantly reduced number of hypergravity-induced vomiting
      episodes compared with Sham animals, the effect was significantly greater in
      Train animals than in Prom animals. Fos expression in the NTS, AP, and PVN were
      significantly more reduced in Train animals than in Prom animals. Higher dose of
      bolus injection of promethazine (50mg/kg, i.p.) completely abolished the vomiting
      episodes, although the animals were drowsy and sedated due to side effects. In
      conclusion, daily linear acceleration training and promethazine could prevent the
      hypergravity-induced vomiting episodes.

PMID- 21741452
TI  - Semantic relatedness between words in each individual brain: an event-related
      potential study.
AB  - The relationship between 2 words is judged by the meanings of words. Here, we
      examined how the semantic relatedness of words is structured in each individual
      brain. During measurements of event-related potentials (ERPs), participants
      performed semantic-relatedness judgments of word pairs. For each participant, we
      divided word pairs into 2 groups--related and unrelated pairs--and compared their
      ERPs. All of the participants showed a significant N400 effect. However, when we
      applied an identical grouping of pairs, this effect was observed only in half the
      number of the participants. These results show that our single-subject analysis
      of N400 extracted semantic relatedness of words in the individual brain. Future
      studies using this analysis will clarify the organization of the mental lexicon.

PMID- 21741454
TI  - Visual responses to contrast-defined contours with equally spatial-scaled carrier
      in cat area 18.
AB  - Contrast-defined contours are one type of second-order contours, across which
      there are no differences in luminance. Although they can be always perceived,
      their responses have been only investigated when the spatial frequency of
      carrier, the background texture whose contrast is modulated to form contours, is
      much higher than that of contrast-defined contours, due to the interference of
      responses to luminance contours in other cases. In the present study, we examined
      visual responses in cat area 18 to the contrast-defined contours with carrier at
      same spatial frequency equal to neuron's preferred value for luminance contours,
      by establishing a control stimulus including all the luminance components but
      lack of the contrast contour information. Using single unit recording and
      intrinsic optical imaging, we demonstrated that contrast gratings with equally
      spatial-scaled carrier induced responses in a proportion of cat area 18 neurons
      with the preferred orientation similar to that for luminance contours, and the
      responses generated orientation maps similar to those for luminance contours. Our
      finding suggests that early visual cortex can process second-order contours
      regardless of the spatial frequency of carriers, in a way similar to the
      processing of luminance contours. This uniform manner of early visual processing
      might underlie the visual detection of both luminance contours and non-luminance
      second-order contours.

PMID- 21741453
TI  - New insights into mechanisms of resistance to microtubule inhibitors.
AB  - Mechanisms to explain tumor cell resistance to drugs that target the microtubule
      cytoskeleton have relied on the assumption that the drugs act either to suppress
      microtubule dynamics or to perturb the balance between assembled and nonassembled
      tubulin. Recently, however, it was found that these drugs also alter the
      stability of microtubule attachment to centrosomes, and do so at the same
      concentrations that are needed to inhibit cell division. Based on this new
      information, a new model is presented that explains resistance resulting from a
      variety of molecular changes that have been reported in the literature. The
      improved understanding of drug action and resistance has important implications
      for chemotherapy with these agents.

PMID- 21741455
TI  - Alzheimer's disease: cholesterol a menace?
AB  - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease
      manifested by cognitive and memory deterioration, culminating in a spectrum of
      neuropsychiatric disturbances and the impairment of daily activities. AD is a
      multifactorial disease with a range of contributing factors which includes genes
      and diet. The magnitude of AD is reflected in the loss of individuality of the
      affected person and in the terminal course through which the disease develops. In
      this review, we aim to provide a background on AD and the contribution of
      cholesterol in the etiology of Alzheimer's. Cholesterol seems to be intimately
      linked with the generation of amyloid plaques, which is central to the
      pathogenesis of AD. Although there are conflicting reports on the role of
      cholesterol in AD, majority of the studies point out the positive association of
      cholesterol with AD.

PMID- 21741456
TI  - The effect of different negative emotional context on involuntary attention: an
      ERP study.
AB  - Event-related brain potentials (ERPs) were used to examine the different negative
      emotional contexts on involuntary attention, induced by a task-irrelevant sound,
      in an auditory-visual distraction paradigm. The emotional contexts comprised sad,
      fearful and neutral, and the irrelevant auditory stimuli consisted of repetitive
      standard sounds (80%) and environmental novel sounds (20%). The present results
      revealed that there were apparently different mismatch negativity (MMN) and
      Novelty-P3 components among these emotional contexts. Specifically, the amplitude
      of MMN showed no significant difference, indicating that the early stage of
      involuntary attention was not affected by the emotional context. Then, the
      amplitude of Novelty-P3, indicating the involuntary orienting of attention to
      novel sounds, attenuated greatest in the sad context. This pattern of results was
      more likely due to the competition for attention resources between affective
      processing and the novel sounds. That is to say, sad inhibit the involuntary
      attention to some extent, whereas perceiving fear cues facilitated novelty
      detection.

PMID- 21741458
TI  - The role of crocetin in protection following cerebral contusion and in the
      enhancement of angiogenesis in rats.
AB  - The protective role of crocetin following cerebral contusion and its effects on
      the enhancement of angiogenesis in rats was investigated. A total of 60 Sprague
      Dawley rats were divided into three groups (n = 20 each): crocetin therapy group
      (cerebral contusion treated with crocetin), cerebral trauma control group
      (without treatment), sham operation control group. The effect of crocetin was
      examined by modified Neurological Severity Scores (mNSS), electron microscopy,
      terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL)
      procedure, western blotting analysis of Bcl-2 protein expression, microvessel
      count (MVC), endothelial cell culture and immunocyto-chemistry. The mNSS results
      indicated that neurological function of therapy group was significantly recovered
      seven days and fifteen days after the trauma. The TUNEL staining and electron
      microscopy revealed that crocetin treatment led to an inhibition of neuronal
      apoptosis 72 h following treatment; this finding was confirmed by western blot
      analysis of B cell lymphoma/leukemia-2 (Bcl-2) protein expression. Expression
      levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and serum
      response factor (SRF) were higher in the crocetin therapy group in comparison to
      the two other experimental groups. Our results demonstrate that the protective
      effects of crocetin upon brain injury may be related to its ability to inhibit
      apoptosis at early stages of the injury and its ability to promote angiogenesis
      at the sub-acute stage.

PMID- 21741457
TI  - Adolescent social defeat alters markers of adult dopaminergic function.
AB  - Stressful experiences during adolescence can alter the trajectory of neural
      development and contribute to psychiatric disorders in adulthood. We previously
      demonstrated that adolescent male rats exposed to repeated social defeat stress
      show changes in mesocorticolimbic dopamine content both at baseline and in
      response to amphetamine when tested in adulthood. In the present study we
      examined whether markers of adult dopamine function are also compromised by
      adolescent experience of social defeat. Given that the dopamine transporter as
      well as dopamine D1 receptors act as regulators of psychostimulant action, are
      stress sensitive and undergo changes during adolescence, quantitative
      autoradiography was used to measure [(3)H]-GBR12935 binding to the dopamine
      transporter and [(3)H]-SCH23390 binding to dopamine D1 receptors, respectively.
      Our results indicate that social defeat during adolescence led to higher dopamine
      transporter binding in the infralimbic region of the medial prefrontal cortex and
      higher dopamine D1 receptor binding in the caudate putamen, while other brain
      regions analyzed were comparable to controls. Thus it appears that social defeat
      during adolescence causes specific changes to the adult dopamine system, which
      may contribute to behavioral alterations and increased drug seeking.

PMID- 21741459
TI  - Space availability influence laterality in donkeys (Equus asinus).
AB  - Cerebral lateralization is the portioning of the cognitive functions between the
      two cerebral hemispheres. Several factors, like embryological manipulations,
      light exposure, health conditions, sex and age can influence the left-right brain
      asymmetries and contribute to increasing the variability in the strength and
      direction of laterality within most species. We investigated the influence of an
      environmental constraint, namely space availability, as a new source of variation
      on laterality in an adult vertebrate model, the donkey. In a baseline condition
      we tested whether donkeys show a motor lateralization bias at population level,
      while in an experimental condition we manipulated space availability to verify if
      a reduction in this parameter could represent a new source of variation in
      laterality. Results show that donkeys are lateralized at population level with a
      strong bias to standing with the right forelimb advanced over the left and that a
      reduction of space availability is an important source of variation in the
      laterality strength and direction within this species. The comparative analysis
      of the environmental and developmental factors that give origin to neural and
      behavioural laterality in animal models will be very important for a better
      understanding of the evolutionary origin of such multifaceted phenomenon.

PMID- 21741460
TI  - Feedback regulation of Ran gene expression by Ran protein.
AB  - Ran, an abundant GTPase that is highly conserved in eukaryotes from yeast to
      human, has been implicated in many aspects of nuclear structure and function.
      Recently it is revealed that the Ran GTPase can regulate the hemocytic
      phagocytosis of shrimp by interaction with myosin. However the regulation of Ran
      gene expression remains unknown. In this study, the promoter of shrimp Ran gene
      was identified which contained a typical TATA box. The results showed that the
      shrimp Ran protein was bound with the Ran promoter in Drosophila S2 cells. Based
      on luciferase assays, our study indicated that the transcription of Ran gene
      could be regulated by the interaction between the Ran promoter and the Ran
      protein, suggesting the existence of a feedback regulation in Ran gene
      expression. Therefore our study presented a novel finding on the feedback
      regulation of gene transcription.

PMID- 21741461
TI  - Preparation and in vitro evaluation of silk fibroin microspheres produced by a
      novel ultra-fine particle processing system.
AB  - The objective of this study was to prepare silk fibroin SF microspheres
      containing the enhanced green fluorescent protein (EGFP) by using a novel ultra
      fine particle processing system (UPPS) and to evaluate the microspheres as
      possible carriers for long-term delivery of sensitive biologicals. The drug
      content, encapsulation efficiency, and in vitro release were evaluated by
      Microplate Absorbance Reader. The particle size distribution and morphology of
      the microspheres were analyzed by Malvern Master Sizer 2000 and scanning electron
      microscopy. The distribution of EGFP and the interactions between SF and EGFP
      were investigated by Confocal Laser Scanning Microscopy, FTIP, Raman and NMR
      spectroscopy. The results showed that spherical microspheres with narrow size
      distribution, glossy and dense surface were successfully manufactured by using
      UPPS technology and over 95% of EGFP encapsulation efficiency and uniform drug
      distribution in the microspheres were achieved. Furthermore, a burst free and
      sustained release of encapsulated EGFP for a period of 50 days in deionized water
      was obtained. In conclusion, the novel UPPS technology could be used to
      manufacture SF matrix microspheres as a potential long-term protein delivery
      system to improve patient compliance and convenience.

PMID- 21741462
TI  - Evaluation of an ethnopharmacologically selected Bhutanese medicinal plants for
      their major classes of phytochemicals and biological activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: As many as 229 medicinal plants have been
      currently used in the Bhutanese Traditional Medicine (BTM) as a chief ingredient
      of polyherbal formulations and these plants have been individually indicated for
      treating various types of infections including malaria, tumor, and microbial. We
      have focused our study only on seven species of these plants. AIM OF THE STUDY:
      We aim to evaluate the antiplasmodial, antimicrobial, anti-Trypanosoma brucei
      rhodesiense and cytotoxicity activities of the seven medicinal plants of Bhutan
      selected using an ethno-directed bio-rational approach. This study creates a
      scientific basis for their use in the BTM and gives foundation for further
      phytochemical and biological evaluations which can result in the discovery of new
      drug lead compounds. MATERIALS AND METHODS: A three stage process was conducted
      which consisted of: (1) an assessment of a pharmacopoeia and a formulary book of
      the BTM for their mode of plant uses; (2) selecting 25 anti-infective medicinal
      plants based on the five established criteria, collecting them, and screening for
      their major classes of phytochemicals using appropriate test protocols; and (3)
      finally analyzing the crude extracts of the seven medicinal plants, using the
      standard test protocols, for their antiplasmodial, antimicrobial, anti
      Trypanosoma brucei rhodesiense and cytotoxicity activities as directed by the
      ethnopharmacological uses of each plant. RESULTS: Out of 25 medicinal plants
      screened for their major classes of phytochemicals, the majority contained
      tannins, alkaloids and flavonoids. Out of the seven plant species investigated
      for their biological activities, all seven of them exhibited mild antimicrobial
      properties, five plants gave significant in vitro antiplasmodial activities, two
      plants gave moderate anti-Trypanosoma brucei rhodesiense activity, and one plant
      showed mild cytotoxicity. Meconopsis simplicifolia showed the highest
      antiplasmodial activity with IC(50) values of 0.40 MUg/ml against TM4/8.2 strain
      (a wild type chloroquine and antifolate sensitive strain) and 6.39 MUg/ml against
      K1CB1 (multidrug resistant strain) strain. Significantly the extracts from this
      plant did not show any cytotoxicity. CONCLUSIONS: These findings provide the
      scientific basis for the use of seven medicinal plants in the BTM for the
      treatment of malaria, microbial infections, infectious fevers, and the
      Trypanosoma brucei rhodesiense infection. The results also form a good
      preliminary basis for the prioritization of candidate plant species for further
      in-depth phytochemical and pharmacological investigations toward our quest to
      unearth lead antiparasitic, anticancer and antimicrobial compounds.

PMID- 21741463
TI  - A(1)H NMR-based metabonomic study on the SAMP8 and SAMR1 mice and the effect of
      electro-acupuncture.
AB  - A (1)H NMR-based metabonomic method was used to investigate the metabolic change
      of plasma in senescence-prone 8 (SAMP8) mice before and after electro-acupuncture
      (EA). Sixteen SAMP8 male mice (aged 8 months) were randomly divided into model
      group and acupuncture treatment group while the later group received EA treatment
      for 21 days. Eight senescence-resistant 1 (SAMR1) mice were used as the control
      group. Morris water maze was used to evaluate the effects of EA. All mice plasma
      samples obtained from different groups were analyzed by using 600 MHz (1)H
      nuclear magnetic resonances ((1)H NMR) spectroscopy. The data sets were analyzed
      by Principal Components Analysis (PCA) and Partial Least Squares-Discriminant
      Analysis (PLS-DA) to discriminate the key plasma metabolites among different
      groups. Results indicated that both the escape and probe tasks of SAMP8 could be
      improved by EA treatment. Metabonomic study showed that SAMR1 and SAMP8 were
      separated clearly in both CPMG_OSC_PLS and LED _OSC_PLS score plots.
      Interestingly, samples obtained from EA group were distributed closely to SAMR1
      group in CPMG_OSC_PLS score plot, but away from SAMP8 group in LED_OSC_PLS score
      plot. Corresponding loading plots showed that much less lactate was seen in SAMP8
      mice plasma. Other changes including higher levels of dimethylamine (DMA) Choline
      and alpha-glucose but lower levels of leucine/isoleucine, HDL, LDL/VLDL, 3
      Hydroxybutyrate (3-HB), and Trimethylamine N-oxide (TMAO) were observed in the
      SAMP8 mice plasma than in the SAMR1. After EA treatment, the levels of lactate,
      DMA, choline and TMAO were improved. Results of this work can provide valuable
      clues to the understanding of the metabolic changes in the senile impairment of
      mice. It is also hoped that the methodology can be used in evaluating the effects
      of EA and understanding the underlying acupuncture mechanism in treating
      neurodegenerative diseases.

PMID- 21741464
TI  - New self-assembly nanoparticles and stealth liposomes for the delivery of
      zoledronic acid: a comparative study.
AB  - Zoledronic acid (ZOL) is a drug whose potent anti-cancer activity is limited by
      its short plasma half-life and rapid uptake and accumulation within bone. We have
      recently proposed new delivery systems to avoid ZOL accumulation into the bone,
      thus improving extra-skeletal bioavailability. In this work, we have compared the
      technological and anti-cancer features of either ZOL-containing self-assembly
      PEGylated nanoparticles (NPs) or ZOL-encapsulating PEGylated liposomes (LIPO
      ZOL). ZOL-containing NPs showed superior technological characteristics in terms
      of mean diameter, size distribution, and ZOL encapsulation efficiency, compared
      to LIPO-ZOL. Moreover, the anti-cancer activity of NPs in nude mice xenografted
      with prostate cancer PC3 cells was higher than that one induced by LIPO-ZOL. In
      addition, NPs induced the complete remission of tumour xenografts and an increase
      of survival time higher than that one observed with LIPO-ZOL. It has also to be
      considered that PC3 tumour xenografts were almost completely resistant to the
      anti-cancer effects induced by free ZOL. Both nanotechnological products did not
      induce toxic effects not affecting the mice weight nor inducing deaths. Moreover,
      the histological examination of some vital organs such as liver, kidney and
      spleen did not find any changes in terms of necrotic effects or modifications in
      the inflammatory infiltrate. On the other hand, NPs but not LIPO-ZOL caused a
      statistically significant reduction of the tumour associated macrophages (TAM) in
      tumour xenografts. This effect was paralleled by a significant increase of both
      necrotic and apoptotic indexes. The effects of the NPs were also higher in terms
      of neo-angiogenesis inhibition. These results suggest the future preclinical
      development of ZOL-encapsulating NPs in the treatment of human cancer.

PMID- 21741466
TI  - Simulation of the Ras/cAMP/PKA pathway in budding yeast highlights the
      establishment of stable oscillatory states.
AB  - In the yeast Saccharomyces cerevisiae, the Ras/cAMP/PKA pathway plays a major
      role in the regulation of metabolism, stress resistance and cell cycle
      progression. We extend here a mechanistic model of the Ras/cAMP/PKA pathway that
      we previously defined by describing the molecular interactions and post
      translational modifications of proteins, and perform a computational analysis to
      investigate the dynamical behaviors of the components of this pathway, regulated
      by different control mechanisms. We carry out stochastic simulations to consider,
      in particular, the effect of the negative feedback loops on the activity of both
      Ira2 (a Ras-GAP) and Cdc25 (a Ras-GEF) proteins. Our results show that stable
      oscillatory regimes for the dynamics of cAMP can be obtained only through the
      activation of these feedback mechanisms, and when the amount of Cdc25 is within a
      specific range. In addition, we highlight that the levels of guanine nucleotides
      pools are able to regulate the pathway, by influencing the transition between
      stable steady states and oscillatory regimes.

PMID- 21741465
TI  - Advances in microfluidic PCR for point-of-care infectious disease diagnostics.
AB  - Global burdens from existing or emerging infectious diseases emphasize the need
      for point-of-care (POC) diagnostics to enhance timely recognition and
      intervention. Molecular approaches based on PCR methods have made significant
      inroads by improving detection time and accuracy but are still largely hampered
      by resource-intensive processing in centralized laboratories, thereby precluding
      their routine bedside- or field-use. Microfluidic technologies have enabled
      miniaturization of PCR processes onto a chip device with potential benefits
      including speed, cost, portability, throughput, and automation. In this review,
      we provide an overview of recent advances in microfluidic PCR technologies and
      discuss practical issues and perspectives related to implementing them into
      infectious disease diagnostics.

PMID- 21741467
TI  - para-Phenylenediamine-induced autophagy in human uroepithelial cell line mediated
      mutant p53 and activation of ERK signaling pathway.
AB  - para-Phenylenediamine (p-PD) is a major aromatic amine that is a widely used
      commercial oxidative-type hair dye. Some epidemiologic studies have suggested
      that the use of p-PD-based hair dyes might be related to increased risk of human
      malignant tumors including bladder cancer. However, the effects of p-PD on
      autophagy in human uroepithelial cells (SV-HUC-1) is still unclear. In this
      study, we demonstrate that p-PD can activate the extracellular signaling
      regulated protein kinase 1/2 (ERK1/2) signaling pathway in SV-HUC-1 cells. In
      addition, we observed that autophagosomes increased in p-PD-treated SV-HUC-1
      cells as shown by electron microscopy. Our results showed incremental increase of
      the concentrations, Beclin-1 and microtubule-associated protein light chain 3B
      (LC3B), which are important regulators of autophagosomes. In contrast, the MEK
      inhibitor (U0126) was suppressed autophagy and the effect of p-PD on ERK1/2,
      Beclin-1 and LC3B proteins expression, except for mutant p53. In this study, we
      demonstrated that inactivation of p53 induces a potent autophagy response.
      Finally, our results suggest that p-PD can activate the ERK1/2 signaling pathway
      and mutant p53, leading to the stimulation of autophagy in SV-HUC-1 cells. These
      results provide us with new insights for the understanding of the mechanism of p
      PD-induced cell death in urothelial cells.

PMID- 21741468
TI  - Trichloroethanol up-regulates matrix metalloproteinase-9 and tissue inhibitor of
      metalloproteinase-1 in HaCaT cells.
AB  - Occupational trichloroethylene (TCE) exposure could induce generalized skin
      hypersensitivity reactions complicated with severe liver dysfunctions. Active
      extracellular matrix degradation and remodeling are involved in the skin
      hypersensitivity reaction induced by chemical exposure. In the present study, we
      have compared the effects of in vitro exposure to trichloroethanol (TCOH) and
      trichloroacetic acid (TCA) of a keratinocyte cell line (HaCaT). The modulation of
      matrix metalloproteinases (MMPs) was selected as marker of sensitization. HaCaT
      cells were treated with different concentrations of TCOH or TCA up to 6days. The
      gelatinolyic activities of MMP-2 and MMP-9 were detected by gelatin-zymography.
      MMP-2, tissue inhibitor of metalloproteinase (TIMP)-2, MMP-9 and TIMP-1 mRNAs
      were analyzed by real-time PCR and MMP-9 and TIMP-1 proteins were tested by
      Western blotting. A dose-effect relationship between TCOH treatment and MMP-9
      activity, mRNA and protein expression levels was found in HaCaT cells. TCOH also
      induced up-regulation of TIMP-1 mRNA and protein. We found no such effects in
      HaCaT cells treated with TCA. Moreover, previously published literatures on patch
      tests suggested that TCOH could induce moderately positive reactions at low
      concentrations in hypersensitivity patients caused by occupational TCE exposure.
      In summary, these observations indicated that TCOH might play an important role
      in TCE-induced skin hypersensitivity.

PMID- 21741469
TI  - The slug mucosal irritation (SMI) assay: development of a screening tool for the
      evaluation of ocular discomfort caused by shampoos.
AB  - In this research, the slug mucosal irritation (SMI) assay was applied to predict
      ocular discomfort caused by shampoos to investigate the correlation between
      responses in slugs and humans. Several SMI experiments and a human eye irritation
      test (HEIT) were performed with 1 artificial tear solution (ArtTear) and 5
      shampoos (A-E; 5%-dilution). In the HEIT, evaluation was performed by
      participants and an ophthalmologist at several time points. Analyses reveal that
      (1) a significant positive association existed between immediate stinging
      reaction reported by the participants and the mean total mucus produced by the
      slugs (MTMP) (Spearman's Rank correlation=0.986, p<0.001); (2) ArtTear was best
      tolerated in both tests; (3) moreover, all shampoos induced higher reactions than
      ArtTear and water; (4) Shampoo A induced the highest MTMP and received higher
      scores for immediate discomfort; (5) B was the best tolerated shampoo in both
      tests, while C, D and E resulted in more pronounced reactions; (6) lacrimation
      was found not to be statistically correlated with discomfort sensations reported
      by the participants. The SMI assay is a promising evaluation method for
      discomfort in the human eye. Screening prototype (eye) formulations with this
      assay allows formula optimization prior to a HEIT.

PMID- 21741470
TI  - Work efficiency: a new criterion for comprehensive comparison and evaluation of
      statistical methods in large-scale identification of differentially expressed
      genes.
AB  - Receiver operating characteristic (ROC) has been widely used to evaluate
      statistical methods, but a fatal problem is that ROC cannot evaluate estimation
      of the false discovery rate (FDR) of a statistical method and hence the area
      under of curve as a criterion cannot tell us if a statistical method is
      conservative. To address this issue, we propose an alternative criterion, work
      efficiency. Work efficiency is defined as the product of the power and degree of
      conservativeness of a statistical method. We conducted large-scale simulation
      comparisons among the optimizing discovery procedure (ODP), the Bonferroni (B-)
      procedure, Local FDR (Localfdr), ranking analysis of the F-statistics (RAF), the
      Benjamini-Hochberg (BH-) procedure, and significance analysis of microarray data
      (SAM). The results show that ODP, SAM, and the B-procedure perform with low
      efficiencies while the BH-procedure, RAF, and Localfdr work with higher
      efficiency. ODP and SAM have the same ROC curves but their efficiencies are
      significantly different.

PMID- 21741471
TI  - A brief relaxation intervention reduces stress and improves surgical wound
      healing response: a randomised trial.
AB  - Psychological stress has been shown to impair wound healing, but experimental
      research in surgical patients is lacking. This study investigated whether a brief
      psychological intervention could reduce stress and improve wound healing in
      surgical patients. This randomised controlled trial was conducted at a surgical
      centre. Inclusion criteria were English-speaking patients over 18 years booked to
      undergo elective laparoscopic cholecystectomy; exclusion criteria were
      cancellation of surgery, medical complications, and refusal of consent. Seventy
      five patients were randomised and 15 patients were excluded; 60 patients
      completed the study (15 male, 45 female). Participants were randomised to receive
      standard care or standard care plus a 45-min psychological intervention that
      included relaxation and guided imagery with take-home relaxation CDs for
      listening to for 3 days before and 7 days after surgery. In both groups ePTFE
      tubes were inserted during surgery and removed at 7 days after surgery and
      analysed for hydroxyproline as a measure of collagen deposition and wound
      healing. Change in perceived stress from before surgery to 7-day follow-up was
      assessed using questionnaires. Intervention group patients showed a reduction in
      perceived stress compared with the control group, controlling for age. Patients
      in the intervention group had higher hydroxyproline deposition in the wound than
      did control group patients (difference in means 0.35, 95% CI 0.66-0.03;
      t(43)=2.23, p=0.03). Changes in perceived stress were not associated with
      hydroxyproline deposition. A brief relaxation intervention prior to surgery can
      reduce stress and improve the wound healing response in surgical patients. The
      intervention may have particular clinical application for those at risk of poor
      healing following surgery.

PMID- 21741472
TI  - TNFalpha is involved in neuropathic pain induced by nucleoside reverse
      transcriptase inhibitor in rats.
AB  - In patients with HIV/AIDS, neuropathic pain is a common neurological
      complication. Infection with the HIV itself may lead to neuropathic pain, and
      painful symptoms are enhanced when patients are treated with nucleoside reverse
      transcriptase inhibitors (NRTIs). The mechanisms by which NRTIs contribute to the
      development of neuropathic pain are not known. In the current studies, we tested
      the role of TNFalpha in antiretroviral drug-induced neuropathic pain. We
      administered 2',3'-dideoxycytidine (ddC, one of the NRTIs) systemically to induce
      mechanical allodynia. We found that ddC induced overexpression of both mRNA and
      proteins of GFAP and TNFalpha in the spinal dorsal horn. TNFalpha was colocalized
      with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of
      TNFalpha with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal
      administration of glial inhibitor or recombinant TNF soluble receptor, reversed
      mechanical allodynia induced by ddC. These results suggest that TNFalpha is
      involved in NRTI-induced neuropathic pain.

PMID- 21741473
TI  - Accumulation of orally administered quercetin in brain tissue and its
      antioxidative effects in rats.
AB  - Quercetin is widely distributed in vegetables and herbs and has been suggested to
      act as a neuroprotective agent. Here, we demonstrate that quercetin can
      accumulate enough to exert biological activity in rat brain tissues. Homogenates
      of perfused rat brain without detectable hemoglobin contaminants were treated
      with beta-glucuronidase/sulfatase and the released quercetin and its methylated
      form were analyzed using high-performance liquid chromatography (HPLC) with three
      different detection methods. Both quercetin and the methylated form were detected
      in the brain of quercetin-administered rats using HPLC-UV and HPLC with
      electrochemical detection and were further identified using HPLC-tandem mass
      spectrometry. Oral administration of quercetin (50mg/kg body wt) attenuated the
      increased oxidative stress in the hippocampus and striatum of rats exposed to
      chronic forced swimming. The possible transport of quercetin derivatives into the
      brain tissue was reproduced in vitro by using a rat brain capillary endothelial
      cell line, a model of the blood-brain barrier. These results show that quercetin
      could be a potent nutrient that can access the brain and protect it from
      disorders associated with oxidative stress.

PMID- 21741474
TI  - Promising effects of the 4HPR-BSO combination in neuroblastoma monolayers and
      spheroids.
AB  - To enhance the efficacy of fenretinide (4HPR)-induced reactive oxygen species
      (ROS) in neuroblastoma, 4HPR was combined with buthionine sulfoximine (BSO), an
      inhibitor of glutathione (GSH) synthesis, in neuroblastoma cell lines and
      spheroids, the latter being a three-dimensional tumor model. 4HPR exposure (2.5
      10 MUM, 24 h) resulted in ROS induction (114-633%) and increased GSH levels (68
      120%). A GSH depletion of 80% of basal levels was observed in the presence of BSO
      (25-100 MUM, 24 h). The 4HPR-BSO combination resulted in slightly increased ROS
      levels (1.1- to 1.3-fold) accompanied by an increase in cytotoxicity (110-150%)
      compared to 4HPR treatment alone. A correlation was observed between the ROS
      inducing capacity of each cell line and the increase in cytotoxicity induced by
      4HPR-BSO compared to 4HPR. No significant correlation between baseline
      antioxidant levels and sensitivity to 4HPR or BSO was observed. In spheroids,
      4HPR-BSO induced a strong synergistic growth retardation and induction of
      apoptosis. Our data show that BSO increased the cytotoxic effects of 4HPR in
      neuroblastoma monolayers and spheroids in ROS-producing cell lines. This
      indicates that the 4HPR-BSO combination might be a promising new strategy in the
      treatment of neuroblastoma.

PMID- 21741475
TI  - Iron-mediated lipid peroxidation and lipid raft disruption in low-dose silica
      induced macrophage cytokine production.
AB  - Silica inhalation can induce respiratory disease. Iron is suspected of playing an
      important role in silica-mediated respiratory toxicity, but unambiguously
      determining its role has been hampered by incomplete characterization, use of
      high particle doses, and lack of understanding of proinflammatory mechanisms. In
      this study, we investigated a novel hypothesis for the mechanism of silica
      particle-induced increase in cytokine production. We studied the role of iron in
      lipid peroxidation-dependent transcription of cytokines in macrophages by ground
      natural silica particles at low sublethal doses. Particle size, size
      distribution, surface area, and structure were determined using electron
      microscopy, nitrogen adsorption, and X-ray diffraction. Iron impurity
      concentrations before and after acid treatment were determined by energy
      dispersive X-ray and inductively coupled plasma mass spectroscopy. At a low
      noncytotoxic dose (1 MUg/ml) of 2-MUm silica, the presence of iron significantly
      increased superoxide (O(2)(*-)), lipid peroxidation, lipid raft disruption, and
      cytokine production in macrophages. The iron chelators deferoxamine mesylate and
      diethylenetriaminepentaacetic acid were found to abrogate O(2)(*-) production and
      inhibit lipid peroxidation, raft disruption, and cytokine induction.
      Tricyclodecan-9-yl xanthate, a competitive inhibitor of phosphatidylcholine
      specific phospholipase C (PC-PLC), which is an upstream participant in NF-kappaB
      activation, and manganese(III) tetrakis(N-ethylpyridinium-2-yl) porphyrin, a
      superoxide dismutase and catalase mimic, blocked silica-stimulated cytokine
      production. We propose a pathway of iron-induced lipid peroxidation disrupting
      lipid rafts and signaling for the production of cytokines through PC-PLC in
      silica-exposed macrophages.

PMID- 21741476
TI  - Persistent behavioral impairment caused by embryonic methylphenidate exposure in
      zebrafish.
AB  - As more adults take the stimulant medication methylphenidate to treat attention
      deficit hyperactivity disorder (ADHD) residual type, the risk arises with regard
      to exposure during early development if people taking the medication become
      pregnant. We studied the neurobehavioral effects of methylphenidate in zebrafish.
      Zebrafish offer cellular reporter systems, continuous visual access and molecular
      interventions such as morpholinos to help determine critical mechanisms
      underlying neurobehavioral teratogenicity. Previously, we had seen that
      persisting neurobehavioral impairment in zebrafish with developmental
      chlorpyrifos exposure was associated with disturbed dopamine systems. Because
      methylphenidate is an indirect dopamine agonist, it was thought that it might
      also cause persistent behavioral impairment after developmental exposure.
      Zebrafish embryos were exposed to the ADHD stimulant medication methylphenidate 0
      5 days post fertilization (12.5-50mg/l). They were tested for long-term
      behavioral effects as adults. Methylphenidate exposure (50mg/l) caused
      significant increases in dopamine, norepinepherine and serotonin on day 6 but not
      day 30 after fertilization. In the novel tank diving test of predatory avoidance
      developmental methylphenidate (50mg/l) caused a significant reduction in the
      normal diving response. In the three-chamber spatial learning task early
      developmental methylphenidate (50mg/l) caused a significant impairment in choice
      accuracy. These data show that early developmental exposure of zebrafish to
      methylphenidate causes a long-term impairment in neurobehavioral plasticity. The
      identification of these functional deficits in zebrafish enables further studies
      with this model to determine how molecular and cellular mechanisms are disturbed
      to arrive at this compromised state.

PMID- 21741477
TI  - Osmotic stabilizer-coupled suppression of NDR defects is dependent on the calcium
      calcineurin signaling cascade in Aspergillus nidulans.
AB  - Establishment and maintenance of cell polarity are coordinated by signaling
      pathways such as NDR (nuclear Dbf2-related) protein-kinase signaling and calcium
      signaling pathway. The NDR family of kinase is structurally related to the human
      myotonic dystrophy kinase, which, when impaired, confers a disease that involves
      changes in cytoarchitecture and ion homeostasis. CotA kinase, a member of the NDR
      protein kinase family, forms a complex with MobB to regulate cell polarized
      growth in Aspergillus nidulans. Our previous study demonstrated that mobB/cotA
      defects could be suppressed by the osmotic stress in the presence of external
      calcium. In this study, via the genetic and molecular approach, we further
      demonstrated that Ca(2+)-permeable stretch-activated nonselective cation channel
      MidA, calcium/calmodulin-dependent protein phosphatase catalatic subunit-CnaA and
      external calcium, but not voltage-gated calcium channel homolog-CchA, were
      required for the osmotic stabilizer-coupled suppression. The up-regulation of
      calcium/calcineurin signaling pathway induced by osmotic stress might be the
      reason for bypassing the requirements of NDR kinase complex, which is otherwise
      necessary for polar morphogenesis. Our results suggest that calcium-calcineurin
      signaling pathway coordinates with MobB/CotA kinase complex in regulating
      polarity growth via maintaining cellular calcium homeostasis. However, CchA may
      act differently as other components in calcium signaling pathway in Aspergillus
      nidulans. These findings provide an excellent opportunity to identify the
      potential pathway linking NDR protein-kinase network to calcium signaling
      pathway.

PMID- 21741478
TI  - Twice switched at birth: cell cycle-independent roles of the "neuron-specific"
      cyclin-dependent kinase 5 (Cdk5) in non-neuronal cells.
AB  - Cdk5 (cyclin-dependent kinase 5 or initially NCLK for neuronal CDC2-like kinase)
      was switched twice at its birth nearly twenty years ago: first it was thought to
      be cyclin-dependent, second it was assumed to be primarily of importance in
      neuronal cells-both turned out not to be the case. In this review we want to
      discuss issues of pharmacological inhibition, to highlight the versatile roles,
      and to summarize the growing evidence for the functional importance of Cdk5 in
      non-neuronal tissues, such as blood cells, tumor cells, epithelial cells, the
      vascular endothelium, testis, adipose and endocrine tissues. The organizing
      principles we follow are apoptosis/cell death, migration/motility, aspects of
      inflammation, and, finally, secretion/metabolism.

PMID- 21741479
TI  - Ranolazine reduces Ca2+ overload and oxidative stress and improves mitochondrial
      integrity to protect against ischemia reperfusion injury in isolated hearts.
AB  - Ranolazine is a clinically approved drug for treating cardiac ventricular
      dysrhythmias and angina. Its mechanism(s) of protection is not clearly understood
      but evidence points to blocking the late Na+ current that arises during ischemia,
      blocking mitochondrial complex I activity, or modulating mitochondrial
      metabolism. Here we tested the effect of ranolazine treatment before ischemia at
      the mitochondrial level in intact isolated hearts and in mitochondria isolated
      from hearts at different times of reperfusion. Left ventricular (LV) pressure
      (LVP), coronary flow (CF), and O2 metabolism were measured in guinea pig isolated
      hearts perfused with Krebs-Ringer's solution; mitochondrial (m) superoxide (O2.
      ), Ca2+, NADH/FAD (redox state), and cytosolic (c) Ca2+ were assessed on-line in
      the LV free wall by fluorescence spectrophotometry. Ranolazine (5 MUM), infused
      for 1 min just before 30 min of global ischemia, itself did not change O2.-,
      cCa2+, mCa2+ or redox state. During late ischemia and reperfusion (IR) O2.-
      emission and m[Ca2+] increased less in the ranolazine group vs. the control
      group. Ranolazine decreased c[Ca2+] only during ischemia while NADH and FAD were
      not different during IR in the ranolazine vs. control groups. Throughout
      reperfusion LVP and CF were higher, and ventricular fibrillation was less
      frequent. Infarct size was smaller in the ranolazine group than in the control
      group. Mitochondria isolated from ranolazine-treated hearts had mild resistance
      to permeability transition pore (mPTP) opening and less cytochrome c release than
      control hearts. Ranolazine may provide functional protection of the heart during
      IR injury by reducing cCa2+ and mCa2+ loading secondary to its effect to block
      the late Na+ current. Subsequently it indirectly reduces O2.- emission, preserves
      bioenergetics, delays mPTP opening, and restricts loss of cytochrome c, thereby
      reducing necrosis and apoptosis.

PMID- 21741480
TI  - The unusual extended C-terminal helix of the peroxisomal alpha/beta-hydrolase
      Lpx1 is involved in dimer contacts but dispensable for dimerization.
AB  - The yeast peroxisomal hydrolase Lpx1 belongs to the alpha/beta-hydrolase
      superfamily. In the absence of Lpx1, yeast peroxisomes show an aberrant
      vacuolated morphology similar to what is found in peroxisomal disorder patients.
      Here, we present the crystal structure of Lpx1 determined at a resolution of 1.9
      A. The structure reveals the complete catalytic triad with an unusual location of
      the acid residue after strand beta6 of the canonical alpha/beta-hydrolase fold. A
      four-helix cap domain covers the active site. The interface between the
      alpha/beta-hydrolase core and the cap domain forms the potential substrate
      binding site, which may also comprise the tunnel that leads into the protein
      interior and widens into a cavity. Two further tunnels connect the active site to
      the protein surface, potentially facilitating substrate access. Lpx1 is a
      homodimer. The alpha/beta-hydrolase core folds of the two protomers form the
      dimer contact site. Further dimerization contacts arise from the mutual
      embracement of the cap domain of one protomer by the non-canonical C-terminal
      helix of the other, resulting in a total buried surface area of some 6000 A2. The
      unusual C-terminal helix sticks out from the core fold to which it is connected
      by an extended flexible loop. We analyzed whether this helix is required for
      dimerization and for import of the dimer into peroxisomes using biochemical
      assays in vitro and a microscopy-based interaction assay in mammalian cells.
      Surprisingly, the C-terminal helix is dispensable for dimerization and dimer
      import. The unusually robust self-interaction suggests that Lpx1 is imported into
      peroxisomes as dimer.

PMID- 21741481
TI  - Age-related changes in the surface morphology of the central sulcus.
AB  - We utilized a sulcus-based computational approach to investigate the relationship
      between the three-dimensional (3D) morphology of the central sulcus (CS) and age.
      The anterior and posterior walls of the CS were manually outlined using high
      resolution magnetic resonance images of 295 right-handed healthy participants
      (age range: 18~94years). Surface reconstruction and parameterization methods were
      employed to create anatomical correspondence of surface locations across
      participants. Four surface metrics, including average sulcal length (SL), surface
      area, fractal dimension (FD) and sulcal span, were used to represent the 3D
      morphology of the CS. We found significant age-related decreases in the surface
      area for all walls of the CS, the SL for posterior walls of the CS and the FD for
      posterior wall of right CS. Age-related increases were found in the sulcal spans
      between the anterior and posterior walls. These surface metrics (except FD)
      exhibited leftward asymmetries. Specifically, age-related changes in surface
      morphology progressed more rapidly in the posterior than in the anterior walls.
      Finally, sex differences were found only in the FD of the right anterior wall of
      the CS. Taken together, our results show age-related changes in the surface
      morphology of the CS and therefore provide insights into the normal aging
      process.

PMID- 21741482
TI  - Reliability of ERP and single-trial analyses.
AB  - A reliable measure is one we can trust in the long run. Thus, the reliability of
      measurements is as important as their validity. Here we investigated the
      reliability of brain electrical visual evoked responses to faces and noise
      textures. For the first time, we provide reliability measures for the full time
      course of event-related potentials (ERPs). Our analyses were also performed on a
      R(2)(t) metric that reflects results from single-trial analyses, therefore
      providing the first reliability analysis of ERP single-trial analyses. Results
      show that ERPs and R(2)(t) are highly reliable (cross-correlation ~0.9, lag
      ~4/6ms, intra-class correlation ~0.9) but also idiosyncratic: ERPs and R(2)(t)
      are highly reproducible within subjects, who differ reliably from each other and
      the grand average across subjects. Consequently, grand averages, although highly
      reliable, can be misleading because they might not reflect the actual brain
      dynamic of any subjects.

PMID- 21741483
TI  - BOLD responses in the superior colliculus and lateral geniculate nucleus of the
      rat viewing an apparent motion stimulus.
AB  - In rats, the superior colliculus (SC) is a main destination for retinal ganglion
      cells and is an important subcortical structure for vision. Electrophysiology
      studies have observed that many SC neurons are highly sensitive to moving
      objects, but complementary non-invasive functional imaging studies with larger
      fields of view have been rarely conducted. In this study, BOLD fMRI is used to
      measure the SC and nearby lateral geniculate nucleus' (LGN) hemodynamic
      responses, in normal adult Sprague Dawley (SD) rats, during a dynamic visual
      stimulus similar to those used in long-range apparent motion studies. The
      stimulation paradigm consists of four light spots arranged in a linear array and
      turned on and off sequentially at different rates to create five effective speeds
      of motion (7, 14, 41, 82, and 164 degrees /s across the visual field). Stationary
      periods (same light spot always on) are interleaved between the moving periods.
      The speed response function (SRF), the hemodynamic response amplitude at each
      speed tested, is measured. Significant responses are observed in the SC and LGN
      at all speeds. In the SC, the SRF increases monotonically from 7 to 82 degrees
      /s. The minimum response amplitude occurs at 164 degrees /s. The results suggest
      that the SC is sensitive to slow moving visual stimuli but the hemodynamic
      response is reduced at higher speeds. In the LGN, the SRF exhibits a similar
      trend to that of the SC, but response amplitude during 7 degrees /s stimulation
      is comparable to that during 164 degrees /s stimulation. These findings are in
      good agreement with previous electrophysiology studies conducted on albino rats
      like the SD strain. This work represents the first fMRI study of stimulus speed
      dependence in the SC and is also the first fMRI study of motion responsiveness in
      the rat.

PMID- 21741484
TI  - The neural correlates of strategic reading comprehension: cognitive control and
      discourse comprehension.
AB  - Neuroimaging studies of text comprehension conducted thus far have shed little
      light on the brain mechanisms underlying strategic learning from text. Thus, the
      present study was designed to answer the question of what brain areas are active
      during performance of complex reading strategies. Reading comprehension
      strategies are designed to improve a reader's comprehension of a text. For
      example, self-explanation is a complex reading strategy that enhances existing
      comprehension processes. It was hypothesized that reading strategies would
      involve areas of the brain that are normally involved in reading comprehension
      along with areas that are involved in strategic control processes because the
      readers are intentionally using a complex reading strategy. Subjects were asked
      to reread, paraphrase, and self-explain three different texts in a block design
      fMRI study. Activation was found in both executive control and comprehension
      areas, and furthermore, learning from text was associated with activation in the
      anterior prefrontal cortex (aPFC). The authors speculate that the aPFC may play a
      role in coordinating the internal and external modes of thought that are
      necessary for integrating new knowledge from texts with prior knowledge.

PMID- 21741485
TI  - Appearance-based modeling for segmentation of hippocampus and amygdala using
      multi-contrast MR imaging.
AB  - A new automatic model-based segmentation scheme that combines level set shape
      modeling and active appearance modeling (AAM) is presented. Since different MR
      image contrasts can yield complementary information, multi-contrast images can be
      incorporated into the active appearance modeling to improve segmentation
      performance. During active appearance modeling, the weighting of each contrast is
      optimized to account for the potentially varying contribution of each image while
      optimizing the model parameters that correspond to the shape and appearance eigen
      images in order to minimize the difference between the multi-contrast test images
      and the ones synthesized from the shape and appearance modeling. As appearance
      based modeling techniques are dependent on the initial alignment of training
      data, we compare (i) linear alignment of whole brain, (ii) linear alignment of a
      local volume of interest and (iii) non-linear alignment of a local volume of
      interest. The proposed segmentation scheme can be used to segment human
      hippocampi (HC) and amygdalae (AG), which have weak intensity contrast with their
      background in MRI. The experiments demonstrate that non-linear alignment of
      training data yields the best results and that multimodal segmentation using T1
      weighted, T2-weighted and proton density-weighted images yields better
      segmentation results than any single contrast. In a four-fold cross validation
      with eighty young normal subjects, the method yields a mean Dice k of 0.87 with
      intraclass correlation coefficient (ICC) of 0.946 for HC and a mean Dice k of
      0.81 with ICC of 0.924 for AG between manual and automatic labels.

PMID- 21741486
TI  - Dissociative neural correlates of semantic processing of nouns and verbs in
      Chinese--a language with minimal inflectional morphology.
AB  - Numerous studies using various techniques and methodologies have demonstrated
      distinctive responses to nouns and verbs both at the behavioral and neurological
      levels. However, since the great majority of these studies involved tasks
      employing pictorial stimuli and languages with rich inflectional morphology, it
      is not clear whether word class effects resulted from semantic differences
      between objects and actions or different inflectional operations associated with
      the two word classes. Such shortcomings were addressed in this study by using a
      language with impoverished inflectional morphology - Chinese. Both concrete and
      abstract words were included, while controlling for nuisance variables between
      the two word classes, including imageability, word frequency, age-of-acquisition,
      and number of stroke. Participants were asked to judge the semantic relatedness
      of noun or verb pairs by pressing different buttons. The results revealed
      specific neural correlates for verb class in left lateral temporal and inferior
      frontal regions. Furthermore, the patterns of neural distribution of nouns and
      verbs were consistent with observations from Indo-European languages. Plausible
      accounts for neural separation of word classes were considered.

PMID- 21741487
TI  - Molecular phylogeny and phylogeography of the Cuban cave-fishes of the genus
      Lucifuga: evidence for cryptic allopatric diversity.
AB  - Underground environments are increasingly recognized as reservoirs of faunal
      diversity. Extreme environmental conditions and limited dispersal ability of
      underground organisms have been acknowledged as important factors promoting
      divergence between species and conspecific populations. However, in many
      instances, there is no correlation between genetic divergence and morphological
      differentiation. Lucifuga Poey is a stygobiotic fish genus that lives in Cuban
      and Bahamian caves. In Cuba, it offers a unique opportunity to study the
      influence of habitat fragmentation on the genetic divergence of stygobiotic
      species and populations. The genus includes four species and one morphological
      variant that have contrasting geographical distributions. In this study, we first
      performed a molecular phylogenetic analysis of the Lucifuga Cuban species using
      mitochondrial and nuclear markers. The mitochondrial phylogeny revealed three
      deeply divergent clades that were supported by nuclear and morphological
      characters. Within two of these main clades, we identified five lineages that are
      candidate cryptic species and a taxonomical synonymy between Lucifuga subterranea
      and Lucifuga teresinarum. Secondly, phylogeographic analysis using a fragment of
      the cytochrome b gene was performed for Lucifuga dentata, the most widely
      distributed species. We found strong geographical organization of the haplotype
      clades at different geographic scales that can be explained by episodes of
      dispersal and population expansion followed by population fragmentation and
      restricted gene flow. At a larger temporal scale, these processes could also
      explain the diversification and the distribution of the different species.

PMID- 21741488
TI  - Prolonged incubation and stacked film exposure improve sensitivity in western
      blotting.
AB  - INTRODUCTION: Western blotting is a basic technique for protein detection. For
      proteins of less abundance or antibodies of poorer quality, an increased
      sensitivity is often desired. Although it is commonly known that higher
      concentrations of antibodies and prolonged film exposure times will help improve
      sensitivity in western blots, both measures come with their own risks, and it is
      often unclear to which extent these measures should be applied. METHODS: We
      conducted time-course studies to investigate protein-antibody interactions and
      primary antibody-secondary antibody interactions in western blotting. We also
      propose a protocol of stacked film exposure and have tested it in standard curves
      and cancer cell samples. RESULTS: Our study found that protein-primary antibody
      interactions and primary antibody-secondary antibody interactions could take a
      longer time than commonly used "one hour" or "overnight", and in some cases
      longer than 48h, to reach its maximum binding. We also show that the modified
      protocol of stacked film exposure works well for both standard curves and
      biological samples, reaching a maximum sensitivity in western blots without
      blurring target signals or increasing backgrounds. DISCUSSION: In addition to
      regular optimization of antibody concentrations and film exposure time, a
      prolonged incubation with antibodies and stacked film exposure will also help
      improve sensitivity and reduce background in western blotting.

PMID- 21741489
TI  - Epidemiology should not be forgotten in osteoarthritis imaging.

PMID- 21741491
TI  - Effects of in vivo exercise on ankle cartilage deformation and recovery in
      healthy volunteers: an experimental study.
AB  - OBJECTIVE: To monitor ankle cartilage 3D volume changes after in vivo exercise
      and during recovery. METHOD: Based on 3D MRI, 3D volumes of talar and tibial
      cartilage were calculated before and after 30 bilateral knee bends in 12 healthy
      volunteers. 3D volumes were calculated at five time points (one pre- and four
      post-scans) determining deformation and recovery for both cartilage plates of
      interest. Post-scans ran immediately after the exercise and were repeated
      according to a 15 min interval. 3D volumes were subjected to repeated measures
      GLM. Additionally, relative surface area use during deformation was compared
      between plates using a Wilcoxon Signed Ranks test and its correlation with
      deformation was investigated using Spearman's rho. RESULTS: Mean 3D volume change
      percentages for talar cartilage after the exercise were: -10.41%, -8.18%, -5.61%
      and -3.90%. For tibial cartilage mean changes were: -5.97%, -5.75%, +0.89% and
      +1.51%. For talar cartilage changes were significant, except following 30 min
      post-exercise. For tibial cartilage no changes were significant. At all time
      points, no significant differences in relative volume changes between both
      cartilage plates existed. Although no significant differences in relative surface
      area use between plates were revealed, a moderate to strong correlation with
      deformation existed. CONCLUSION: Ankle cartilage endures substantial deformation
      after in vivo loading that was restored within 30 min for the talus. Overall
      cartilage contact area involvement might be associated with cartilage quality
      maintenance in the upper ankle. Talar cartilage is suggested to play a critical
      role in intra-articular shock attenuation when compared to tibial cartilage.

PMID- 21741492
TI  - Dissociable contributions of the left and right posterior medial orbitofrontal
      cortex in motivational control of goal-directed behavior.
AB  - Several findings from both human neuroimaging and nonhuman primate studies
      suggest that the posterior medial orbitofrontal cortex (OFC) may be critical for
      the motivational control of goal-directed behavior. The present study was
      conducted to clarify the role of the left and right posterior medial OFC in that
      function by examining the effects of focal unilateral lesions to this region on
      the performance on an incentive working memory task. The study covered patients
      who had undergone surgery for an ACoA aneurysm and normal control subjects (C).
      The patients were subdivided into three groups: those with resection of the left
      (LGR+) or right (RGR+) posterior part of the gyrus rectus, and without such a
      resection (GR-). Participants performed a 2-back working memory task under three
      motivational conditions (penalty, reward, and no-incentive). The C group
      performed worse in the penalty condition and better in the reward condition as
      compared to the no-incentive condition. Similar results were obtained for the GR-
      group. Performance of the LGR+ group did not depend on incentive manipulations,
      whereas the RGR+ group performed better in both the penalty and reward conditions
      than in the no-incentive condition. The results show that the posterior medial
      OFC is involved in the motivational modulation of working memory performance. Our
      findings also suggest that the left posterior medial OFC plays a crucial role in
      this function, whereas the right posterior medial OFC is particularly involved in
      the processing of the punishing aspect of salient events and it probably mediates
      in guiding behavior on the basis of negative outcomes of action.

PMID- 21741493
TI  - Determinants of insulin responsiveness in young women: Impact of polycystic
      ovarian syndrome, nitric oxide, and vitamin D.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with incremental risk
      of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR)
      occurs frequently in PCOS subjects, which might be one of the mechanisms involved
      in engendering such risk. We sought to evaluate whether the impact of other
      factors potentially associated both with PCOS and with IR might differentially
      modulate degree of IR in women with and without PCOS. METHODS AND RESULTS: We
      measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric
      dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness
      to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women
      (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome,
      hypertension or overt cardiovascular disease. We performed univariate and
      multivariate regression analyses to establish correlates of the quantitative
      insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate
      analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct
      correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels
      were significant inverse correlates of QUICKI in PCOS subjects, but not in
      subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3
      levels, but not PCOS per se were significant correlates of QUICKI. CONCLUSIONS:
      In the entire cohort of young women, low NO responsiveness and vitamin D
      deficiency are associated with low QUICKI, while elevated ADMA, inflammatory
      activation and obesity are selectively associated with low QUICKI in PCOS
      subjects; this may contribute to the increased cardiovascular risk associated
      with this syndrome.

PMID- 21741494
TI  - A stable yeast strain efficiently producing cholesterol instead of ergosterol is
      functional for tryptophan uptake, but not weak organic acid resistance.
AB  - Sterols are major lipids in eukaryotes and differ in their specific structure
      between species. Both cholesterol and ergosterol can form liquid ordered domains
      in artificial membranes. We reasoned that substituting the main sterol ergosterol
      by cholesterol in yeast should permit domain formation and discriminate between
      physical and sterol structure-dependent functions. Using a cholesterol-producing
      yeast strain, we show that solute transporters for tryptophan and arginine are
      functional, whereas the export of weak organic acids via Pdr12p, a multi-drug
      resistance family member, is not. The latter reveals a sterol function that is
      probably dependent upon a precise sterol structure. We present a series of novel
      yeast strains with different sterol compositions as valuable tools to
      characterize sterol function and use them to refine the sterol requirements for
      Pdr12p. These strains will also be improved hosts for heterologous expression of
      sterol-dependent proteins and safe sources to obtain pure cholesterol and other
      sterols.

PMID- 21741495
TI  - Is informed consent necessary for randomized Phase IV 'observational' drug
      studies?
AB  - This article addresses the question about whether informed consent (IC) can be
      waived in Phase IV randomized observational drug studies (P4RODSs). To do this,
      it was first necessary to establish that the term P4RODS is a contradiction
      precisely because randomization necessarily makes a study 'interventional', hence
      P4RIDS. Once this was established we argued that, based on the right and the harm
      principles, universally waiving IC in P4RIDS is ethically unjustifiable. Looking
      into public health and the nature of equipotent and bioequivalent drugs were also
      insufficient rationale to justify circumstantial waiving of IC. We conclude that
      IC can never be waived in P4RIDS, although an opt-out procedure in minimal risk
      studies could be ethically acceptable.

PMID- 21741496
TI  - Clonorchis sinensis and clonorchiasis, an update.
AB  - Clonorchis sinensis is the most common human liver fluke in East Asia. Several
      studies proved its carcinogenesis in humans and it was reclassified as a group 1
      biological carcinogen in 2009. It is still actively transmitted in endemic areas
      of Korea, China, Russia, and Vietnam. Currently it is estimated that more than
      200 million people are at risk of infection, 15-20 million people are infected
      and 1.5-2 million show symptoms or complications. Several molecules and genes of
      the fluke have been identified and characterized. Studies on its oncogenesis and
      omics-based findings have been especially encouraging. Diagnosis of its infection
      depends mainly on detection of eggs in feces but other methods have been
      developed. ELISA using crude extract antigen is now popular for its diagnosis.
      Diagnosis by detecting DNAs from eggs in feces has been developed using PCR, real
      time PCR, and LAMP, which have been found sensitive and specific. Imaging
      diagnosis has been studied in depth and is widely used. Any evidence of
      clonorchiasis, such as eggs, DNAs, or images, may lead to recommendations of
      chemotherapy in endemic areas. Praziquantel is the major chemotherapeutic agent
      for clonorchiasis and recently tribendimidine was found effective and is now
      under investigation as a promising chemotherapeutic alternative. Sustainable
      control programs which include mass chemotherapy with praziquantel and education
      for prevention of re-infection may reduce its morbidity and eliminate its
      infections in endemic areas.

PMID- 21741497
TI  - Detection of antinuclear antibodies by indirect immunofluorescence and by solid
      phase assay.
AB  - Testing for antinuclear antibodies is useful for the diagnosis of systemic
      rheumatic diseases. Solid phase assays are increasingly replacing indirect
      immunofluorescence for detection of antinuclear antibodies. In the most recent
      generation of solid phase assays, manufacturers attempt to improve the
      performance of the assays by adding extra antigens. Solid phase assay (EliA CTD
      Screen, Phadia, in which antibodies to 17 antigens are detected) was compared to
      indirect immunofluorescence for the detection of antinuclear antibodies in
      diagnostic samples of 236 patients with autoimmune connective tissue diseases, in
      149 healthy blood donors, 139 patients with chronic fatigue syndrome, and 134
      diseased controls. The sensitivity of EliA CTD Screen for systemic lupus
      erythematosus, systemic sclerosis, primary Sjogren's syndrome, mixed connective
      tissue disease, and inflammatory myopathy was 74%, 72%, 89%, 100%, and 39%,
      respectively. The reactivity in blood donors, in patients with chronic fatigue
      syndrome, and in diseased controls was <4%. Likelihood ratios increased with
      increasing antibody concentrations. Generally, a positive test result by EliA CTD
      Screen had a higher likelihood ratio for systemic rheumatic disease than a
      positive test result by indirect immunofluorescence. A negative test result by
      indirect immunofluorescence, however, had a lower likelihood ratio than a
      negative test result by EliA CTD Screen, indicating that the negative predictive
      value was higher for indirect immunofluorescence than for EliA CTD screen.

PMID- 21741498
TI  - Italian multicentre study for application of a diagnostic algorithm in
      autoantibody testing for autoimmune rheumatic disease: conclusive results.
AB  - AIM: The presence of specific auto-antibodies in serum (i.e., antinuclear
      antibodies or ANA, anti-extractable nuclear antigens or anti-ENA, and anti-double
      stranded DNA or anti-dsDNA ) is one of the major criteria in the diagnostics of
      Autoimmune Rheumatic Disease. As such, the request for these tests has grown
      exponentially in laboratory practice. The aim of this study is to describe the
      implementation of a joint laboratory-clinics guideline for reducing clinically
      inappropriate requests for autoantibody testing in a broad geographic area
      (Parma, Modena, Piacenza, Reggio-Emilia) for the diagnosis of Autoimmune
      Rheumatic Disease. METHODS: This study, supported by a Regional grant for
      innovative research projects started in January 2008, is an observational
      research aimed at comparing the number of ANA, anti-dsDNA and anti-ENA testing as
      well as the percentage of positive test results before and after implementation
      of the diagnostic algorithm in hospitalized patients. A multidisciplinary team
      consisting of clinical immunologist and laboratory scientists was established,
      with the aim of collecting and analysing diagnostic criteria, clinical needs,
      laboratory report formats, analytical procedures, as well as the number of tests
      performed. The laboratory results and the clinical protocol were both validated
      by data emerging from the clinical follow-up studies. RESULTS: A joint guideline
      for auto-antibody testing, placing ANA test at the first level, has been
      developed and implemented since January 2009. The results for the period January
      June 2009 (12,738 tests) were compared with those of the same period in 2008
      (13,067 tests). A significant reduction in the number of anti-dsDNA (-26%) and
      anti-ENA (-15%) was observed. The percentage of second-level tests positivity
      after implementation of the diagnostic protocol had also consistently increased
      for both ENA (13% vs 17%) and dsDNA (9% vs 11%). DISCUSSION: The development and
      implementation of algorithms for the diagnostics of Autoimmune Rheumatic Disease
      in hospitalized patients was associated with a reduction in the number of second
      level tests, but also with an increased diagnostic specificity. This outcome
      attests that close collaboration and audit between clinicians, laboratory
      specialists and healthcare services is effective to develop efficient diagnostic
      algorithms for both hospitalized patients and outpatients.

PMID- 21741499
TI  - Respiratory related control of hypoglossal motoneurons--knowing what we do not
      know.
AB  - Because tongue position and stiffness help insure that the pharyngeal airspace is
      sufficiently open during breathing, the respiration-related behavior of the
      tongue muscles has been studied in detail, particularly during the last two
      decades. Although eight different muscles act upon the mammal tongue, we know
      very little about the respiration-related control of the majority of these, and
      almost nothing about how they work together as a complex electro-mechanical
      system. Other significant gaps include how hypoglossal motoneuron axons find
      their appropriate muscle target during development, whether the biophysical
      properties of hypoglossal motoneurons driving different muscles are the same, and
      how afferent information from cardiorespiratory reflex systems is transmitted
      from major brainstem integrating centers to the hypoglossal motoneuron pool. This
      brief review outlines some of these issues, with the hope that this will spur
      research in the field, ultimately leading to an improved understanding of the
      respiration-related control of the mammalian tongue musculature.

PMID- 21741500
TI  - Effect of supine posture on airway blood flow and pulmonary function in stable
      heart failure.
AB  - BACKGROUND: The aim of this study was to determine the relationship between body
      position, pulmonary function (PF) and bronchial blood flow (Q(aw)) in a group of
      heart failure (HF) and control subjects. METHODS: Thirty-six subjects were
      studied: 24 stable, ambulatory HF patients (HF: LVEF=27+/-6%, age=65+/-9 yr) and
      12 age- and sex-matched controls (CTRL: LVEF=60+/-7%, age=62+/-8 yr). Measures of
      Q(aw) (soluble gas method) and PF were collected upright and following 30min in
      the supine position. RESULTS: Q(aw) was similar between groups and remained
      unchanged with body position. Declines in forced vital capacity (FVC) and forced
      expiratory volume in 1s (FEV1) with the supine position were observed in both
      groups; declines in forced expiratory flow 25-75% (FEF(25-75)) and FEF 75%
      (FEF75) with the supine position were observed in the HF group only. Changes in
      Q(aw) were related to changes in PF only in the HF patient groups (DeltaFVC, %
      predicted, r = -0.45, p<0.04, DeltaFEV1 r = -0.61, p<0.01, DeltaFEV1% predicted,
      r = -0.45, p<0.04). CONCLUSION: These data demonstrate that relationships between
      postural changes in Q(aw) and PF exist only in the HF population and that the
      bronchial circulation may contribute to postural PF decline in HF.

PMID- 21741501
TI  - Genotype-phenotype correlation in 13q13.3-q21.3 deletion.
AB  - Pure interstitial deletions of the long arm of chromosome 13 are correlated with
      variable phenotypes according to the size and the location of the deleted region.
      Deletions involving the 13q13q21 region are rare. In order to establish
      interstitial 13q genotype-phenotype correlation, we used high resolution 244K
      oligonucleotide array in addition to conventional karyotype and molecular
      (fluorescent in situ hybridization, microsatellite markers analysis) techniques
      in two independent probands carrying a deletion 13q13 to 13q21. First patient was
      a 3-year-old girl with mental retardation and dysmorphy carrying a 13q13.3q21.31
      de novo deletion diagnosed post-natally. The second one was a fetus with de novo
      del(13)(q14q21.2) associated with first trimester increased nuchal translucency.
      We showed that specific dysmorphic features (macrocephaly, high forehead,
      hypertelorism, large nose, large and malformed ears and retrognathia) were
      correlated to the common 13q14q21 chromosomal segment. Physical examination
      revealed overgrowth with global measurement up to the 95th percentile in both
      probands. This is the second description of overgrowth in patients carrying a 13q
      deletion. Haploinsufficiency of common candidates genes such as CKAP2, SUGT1,
      LECT1, DCLK1 and SMAD9, involved in cell division and bone development, is a
      possible mechanism that could explain overgrowth in both patients. This study
      underlines also that cytogenetic analysis could be performed in patients with
      overgrowth.

PMID- 21741502
TI  - Stromal cell-derived factor-1 enhances distraction osteogenesis-mediated skeletal
      tissue regeneration through the recruitment of endothelial precursors.
AB  - Distraction osteogenesis (DO) is a unique therapy that induces skeletal tissue
      regeneration without stem/progenitor cell transplantation. Although the self
      regeneration property of DO provides many clinical benefits, the long treatment
      period required is a major drawback. A high-speed DO mouse model (H-DO), in which
      the distraction was done two times faster than in control DO (C-DO) mice, failed
      to generate new bone callus in the DO gap. We found that this was caused by the
      unsuccessful recruitment of bone marrow endothelial cells (BM-ECs)/endothelial
      progenitor cells (EPCs) into the gap. We then tested the ability of a local
      application of stromal cell-derived factor-1 (SDF-1), a major chemo-attractant
      for BM-ECs/EPCs, to accelerate the bone regeneration in H-DO. Our data showed
      that, in H-DO, SDF-1 induced callus formation in the gap through the recruitment
      of BM-ECs/EPCs, the maturation of neo-blood vessels, and increased blood flow.
      These results indicate that the active recruitment of endogenous BM-ECs/EPCs may
      provide a substantial clinical benefit for shortening the treatment period of DO.

PMID- 21741503
TI  - Transiliac hernia.
AB  - Lumbar hernias (and namely transiliac hernias) are not frequent. We report the
      case of a 76-year-old man presenting with an incarcerated transiliac hernia, in a
      context of exacerbated chronic obstructive pulmonary disease, 30 years after
      iliac bone harvesting for femur surgery. After imaging, the patient underwent a
      laparotomy, and a herniated left colic segment was identified through a hole in
      the left iliac crest. The left colon was reduced and the defect was closed by an
      omental patch. The patient recovered well and was discharged. Graft-site hernia
      is a rare complication of harvesting bone grafts from the iliac crest. Repeated
      increases in abdominal pressure can result in herniation of abdominal contents
      through the osseous defect. Computed tomography is commonly used to confirm the
      diagnosis.

PMID- 21741504
TI  - Torsion of a huge pedunculated uterine leiomyoma.
AB  - Uterine leiomyoma in torsion is an uncommon emergency and mimics generalized
      peritonitis. We report the case of a 62-year-old woman with a huge subserous
      fibroid in torsion. The lesion was removed surgically with the uterus and
      ovaries. Imaging is an essential tool in the diagnosis of myomata and should
      serve to exclude other diseases, especially malignancy.

PMID- 21741505
TI  - The surgical residency and Accreditation Council for Graduate Medical Education
      reform: steep learning or sleep learning?

PMID- 21741506
TI  - Preserving the quality of training surgical residents.

PMID- 21741507
TI  - Resident duty-hour restrictions.

PMID- 21741508
TI  - Training surgeons: have we reached the tipping point?

PMID- 21741509
TI  - Protection of stapled colorectal anastomoses with a biodegradable device: the C
      Seal feasibility study.
AB  - BACKGROUND: A colorectal anastomotic leak can be life-threatening. We have
      assessed the feasibility of a new intraluminal biodegradable bypass device that
      we designed to avoid anastomotic leakage and the necessity of a temporary stoma.
      METHODS: Fifteen patients underwent colorectal surgery. Before performing the
      anastomosis in a standard way, the C-Seal (Polyganics BV, Groningen, The
      Netherlands) was glued to the anvil of the circular stapler. Consequently, the
      bypass was fixated in the staple row just proximal of the simultaneously made
      anastomosis. A water-soluble contrast enema was performed after 1 week. RESULTS:
      The sheath was well compatible with the standard stapler device and easy to use.
      All donuts remained intact. No radiologic or clinical leaks were observed after
      surgery. CONCLUSIONS: This pilot study shows that the C-Seal can be applied
      successfully in colorectal surgery. Further investigation with large numbers of
      patients is now necessary to assess the efficacy of the C-Seal as a protective
      device.

PMID- 21741510
TI  - Clinical management of occult hemothorax: a prospective study of 81 patients.
AB  - BACKGROUND: Intrapleural blood detected by computed tomography scan, but not
      evident on plain chest radiograph, defines occult hemothorax. This study
      determined the role for tube thoracostomy. METHODS: Hemothorax was quantified on
      computed tomography by measuring the deepest lamellar fluid stripe at the most
      dependent portion. Data were collected prospectively on demographics, injury
      mechanism/severity, chest injuries, mechanical ventilation, hospital length of
      stay, complications, and outcome. Indications for tube thoracostomy were
      recorded. RESULTS: Tube thoracostomy was avoided in 67 patients (83%).
      Indications for chest tube placement included progression of hemothorax (8),
      desaturation (4), and delayed hemothorax (2). Patients with intrapleural fluid
      thickness greater than 1.5 cm were 4 times more likely to require tube
      thoracostomy. CONCLUSIONS: Occult hemothorax can be managed successfully without
      tube thoracostomy in most cases. Mechanical ventilation is not an indication for
      chest tube placement. Accompanying occult pneumothorax may be expected in 50% of
      cases, but did not affect clinical management.

PMID- 21741511
TI  - Age matters: a study of clinical and economic outcomes following cholecystectomy
      in elderly Americans.
AB  - BACKGROUND: Gallstone disease increases with age. The aims of this study were to
      measure short-term outcomes from cholecystectomy in hospitalized elderly
      patients, assess the effect of age, and identify predictors of outcomes. METHODS:
      This was a cross-sectional analysis, using the Health Care Utilization Project
      Nationwide Inpatient Sample (1999-2006), of elderly patients (aged 65-79 and >=80
      years) and a comparison group (aged 50-64 years) hospitalized for
      cholecystectomy. Linear and logistic regression models were used to evaluate age
      and outcome relationships. Main outcomes were in-hospital mortality,
      complications, discharge disposition, mean length of stay, and cost. RESULTS: A
      total of 149,855 patients aged 65 to 79 years, 62,561 patients aged >= 80 years,
      and 145,675 subjects aged 50 to 64 years were included. Elderly patients had
      multiple biliary diagnoses and longer times to surgery from admission and
      underwent more open procedures. Patients aged 65 to 79 years and those aged >=80
      years had higher adjusted odds of mortality (odds ratios [ORs], 2.36 and 5.91,
      respectively), complications (ORs, 1.57 and 2.39), nonroutine discharge (ORs,
      3.02 and 10.76), longer length of stay (ORs, 1.11 and 1.31), and higher cost
      (ORs, 1.09 and 1.22) than younger patients. CONCLUSIONS: Elderly patients
      undergoing inpatient cholecystectomy have complex disease, with worse outcomes.
      Longer time from admission to surgery predicts poor outcome.

PMID- 21741512
TI  - Appendiceal carcinoid at a large tertiary center: pathologic findings and long
      term follow-up evaluation.
AB  - BACKGROUND: Appendiceal carcinoid tumor is the most common type of primary
      appendiceal malignant lesion. Nonetheless; it is an exceedingly rare diagnosis;
      found in only about .3% to .9% of appendectomy specimens. We report the clinical
      and pathologic characteristics of carcinoids found with long-term follow-up
      evaluation. METHODS: Data of patients who were histologically reported to have
      carcinoid tumor of the appendix; in a single center; during a 16-year period were
      collected retrospectively. In addition; patients were contacted for current
      follow-up information. RESULTS: A total of 44 patients were diagnosed with
      appendiceal carcinoid during the study period. The median follow-up period for
      the cohort was 7 years. No evidence of any recurrent disease or other
      noncarcinoid neoplasm was found. CONCLUSIONS: Our data confirm the good prognosis
      as seen in earlier reports. The long-term significance of having a carcinoid; and
      whether this poses a risk for future neoplasms; need even longer-term studies.

PMID- 21741513
TI  - Robot-assisted distal gastrectomy for gastric cancer: initial experience.
AB  - BACKGROUND: This study evaluated the feasibility and safety of robotic surgery in
      gastrectomy for gastric cancer. METHODS: Between April and October 2009, 12
      patients who were diagnosed with stage I gastric cancer underwent robot-assisted
      distal gastrectomy (RADG) using the da Vinci System (Intuitive Surgical,
      Sunnyvale, CA). The clinical and pathological characteristics of the patients and
      surgical outcome were analyzed. RESULTS: All procedures were completed
      successfully, with no laparoscopic or open conversion. The mean operating time
      was 253 minutes (range 170-365), and the mean blood loss was 135 mL (range 30
      500). The resection margin was negative in all specimens, and a mean of 46 (range
      21-115) lymph nodes was retrieved. The mean time to resume a soft diet and
      hospital stay was 4.6 and 6.6 days, respectively. Acute pancreatitis occurred in
      1 patient and resolved with conservative management. CONCLUSIONS: In our initial
      experience, RADG was feasible, enabling a fast patient recovery and good
      operative outcome.

PMID- 21741514
TI  - Neurofibroma of the common bile duct: a rare cause of obstructive jaundice.
AB  - Neurofibroma of the common bile duct is extremely rare. Fewer than 20 cases have
      been reported in the literature. We report a case of neurofibroma in a 47-year
      old female presented with obstructive jaundice. Preoperative imaging failed to
      diagnose the case. The patient was treated with en-bloc excision of the
      extrahepatic biliary tree and Roux-en-Y hepaticojejunostomy.

PMID- 21741515
TI  - Multiple aortic atherosclerosis penetrating an ulcer.
AB  - Our patient had a left chest and back pain for more than 2 months, which had
      worsened during the previous month. Arteriae aorta CT angiography (CTA) diacrisis
      was as follows: (1) the aorta pectoralis protruded in local and parts of
      interparietal blood tumor emerged, the arterial canal paries calcified, may be
      the aortic atherosclerosis penetrating ulcer; (2) the low density of the
      abdominal aorta change, may be the interparietal blood tumor. During the surgery,
      according to the digital subtraction angiography (DSA) angiography, the aorta
      descendens penetrating ulcer emerged and the dissection of aorta formed at the
      remote end of the left subclavian artery, and an anabrosis also emerged 13 cm
      away from the remote end. The celiac axis also had an anabrosis, and combined
      with CTA, we decided to perform an isolation surgery, inserting the intracavitary
      bracket in the aorta pectoralis intracavitary. During the 6-month follow-up
      period, there was no pain or discomfort, with CTA re-examination, the bracket
      could be found at the range from the aortic arch to the inferior segment of aorta
      pectoralis.

PMID- 21741516
TI  - Invited commentary on Hwang U et al: factors associated with delays to emergency
      care for bowel obstruction-we have issues.

PMID- 21741517
TI  - Predictors of mesh explantation after incisional hernia repair.
AB  - BACKGROUND: Prosthetic mesh used for incisional hernia repair (IHR) reduces
      hernia recurrence. Mesh infection results in significant morbidity and challenges
      for subsequent abdominal wall reconstruction. The risk factors that lead to mesh
      explantation are not well known. METHODS: This is a multisite cohort study of
      patients undergoing IHR at 16 Veterans Affairs hospitals from 1998 to 2002.
      RESULTS: Of the 1,071 mesh repairs, 55 (5.1%) had subsequent mesh explantation at
      a median of 7.3 months (interquartile range 1.4-22.2) after IHR with permanent
      mesh prosthesis. Infection was the most common reason for explantation (69%). No
      differences were observed by the type of repair. Adjusting for covariates, same
      site concomitant surgery (hazard ratio [HR] = 6.3) and postoperative surgical
      site infection (HR = 6.5) were associated with mesh explantation. CONCLUSIONS:
      Patients undergoing IHR with concomitant intra-abdominal procedures have a
      greater than 6-fold increased hazard of subsequent mesh explantation. Permanent
      prosthetic mesh should be used with caution in this setting.

PMID- 21741518
TI  - Indication for sentinel lymph node biopsy for breast cancer when core biopsy
      shows ductal carcinoma in situ.
AB  - BACKGROUND: The use of sentinel lymph node biopsy (SLNB) for ductal carcinoma in
      situ (DCIS) is controversial. METHODS: A total of 103 primary breast cancer
      patients who were diagnosed with DCIS by needle biopsy preoperatively and
      underwent initial SLNB were analyzed retrospectively. RESULTS: No sentinel nodal
      metastasis was detected in 66 patients with the final diagnosis of DCIS. However,
      2 (5.4%) of 37 patients with invasive ductal carcinoma at final diagnosis had
      positive sentinel nodes. Multivariate logistic regression analysis identified 2
      independent significant predictors of existence of invasive components: presence
      of a palpable tumor (odds ratio, 4.091; 95% confidential interval, 1.399-11.959;
      P = .010) and tumor size of 2.0 cm or larger on magnetic resonance imaging (odds
      ratio, 4.506; 95% confidence interval, 1.322-15.358; P = .016). CONCLUSIONS:
      Initial SLNB should be considered for patients diagnosed with DCIS by needle
      biopsy when they have a high risk for harboring invasive ductal cancer
      preoperatively.

PMID- 21741519
TI  - Randomized clinical trial of vessel sealing system (LigaSure) in esophagogastric
      devascularization and splenectomy in patients with portal hypertension.
AB  - BACKGROUND: The LigaSure vessel sealing system (Valleylab, Boulder, CO) has been
      tested, with excellent results, in different fields of surgery. However, no study
      has evaluated the efficiency of the LigaSure in open esophagogastric decongestion
      and splenectomy in a randomized trial to date. METHODS: Patients scheduled to
      undergo esophagogastric decongestion and splenectomy were assigned to the use of
      either the LigaSure or a conventional clamp-and-tie technique. Primary outcome
      measures were operating time and intraoperative blood loss. Secondary outcome
      measures were postoperative drainage volume, complications such as spleen fever,
      bleeding, portal vein thrombosis, length of incision, pain, and time to
      discharge. RESULTS: Sixty patients were randomized to the LigaSure (n = 30) and
      clamp-and-tie (n = 30) groups. The groups were well matched with respect to liver
      function, associated illnesses, and grading of esophageal varices. Postoperative
      outcomes in drainage and major complications did not differ between the groups,
      while operative time and the volume of blood loss were significantly decreased in
      the LigaSure group compared with the clamp-and-tie group (P < .001). CONCLUSIONS:
      The use of the LigaSure is safe and effective in vessel division and homeostasis
      in the esophagogastric decongestion and splenectomy, with statistically
      significant decreases in operative time and intraoperative blood loss and without
      significantly modifying postoperative results.

PMID- 21741520
TI  - Evaluation of serum cytokine release in response to hand-assisted, laparoscopic,
      and open surgery in a porcine model.
AB  - BACKGROUND: Although the immunologic benefits of laparoscopic surgery have been
      established, effects from hand-assisted (HA) surgery have not been investigated
      thoroughly. We hypothesized that the HA approach maintains the immunologic
      advantage of laparoscopic surgery compared with the open (O) approach. METHODS:
      Six O, HA, and laparoscopic (L) transabdominal left nephrectomies were performed
      on pigs. Blood samples were taken preoperatively, perioperatively, and
      postoperatively, and serum interleukin-6 and C-reactive protein levels were
      measured. RESULTS: At 24 hours after surgery, interleukin-6 levels were
      significantly higher in the O group vs the HA and L groups (82.2 vs 37.5 and 29.9
      pg/mL, respectively; P < .05). Similar trends were seen at all time periods for
      both IL-6 and C-reactive protein. No significant differences in postoperative
      cytokine levels were detected between the HA and L groups. CONCLUSIONS: The HA
      approach mimics the immunologic effects of laparoscopic surgery. These data
      suggest that the HA technique resulted in a reduced systemic immune activation in
      the early perioperative period when compared with open surgery. In addition to
      clinical benefits of minimal access, the HA approach also may afford patients an
      immunologic advantage over laparotomy.

PMID- 21741521
TI  - Experimental animal study of a novel radiofrequency endovascular occlusion
      device.
AB  - BACKGROUND: The purpose of this study was to present a radiofrequency (RF)
      endovascular occlusion device (ie, Habib VesCoag Catheter; EMcision Ltd, London,
      UK) and to evaluate safety and efficacy of the device for complete occlusion of
      normal porcine vessels. METHODS: The study included 20 pigs. In each pig, a
      segmental branch of the right hepatic artery, a branch of the splenic artery, and
      a branch of one of the renal arteries were catheterized. A single or multiple
      applications of RF energy were performed until vessel occlusion was achieved.
      Fifteen days later, angiography was repeated to assess vessel patency. The
      vessels were then excised for pathological analysis. RESULTS: Vessels 2.5 to 6 mm
      in diameter were treated. Complete occlusion with a single attempt was achieved
      using a mean amount of energy of 110.67 J in vessels 2.5 to 3 mm, 111.67 J in
      vessels 3.5 to 4 mm, and 116.63 J in vessels 5 to 6 mm in diameter and was
      confirmed by angiography at the 15-day follow-up. CONCLUSIONS: Vascular occlusion
      can be effectively and safely achieved by endovascular application of RF energy
      to normal porcine arteries using the Habib VesCoag catheter.

PMID- 21741540
TI  - Enhancing performance for action and perception--multisensory integration,
      neuroplasticity and neuroprosthetics, Part I. Preface.

PMID- 21741541
TI  - Naturalistic approaches to sensorimotor control.
AB  - Human sensorimotor control has been predominantly studied using fixed tasks
      performed under laboratory conditions. This approach has greatly advanced our
      understanding of the mechanisms that integrate sensory information and generate
      motor commands during voluntary movement. However, experimental tasks necessarily
      restrict the range of behaviors that are studied. Moreover, the processes studied
      in the laboratory may not be the same processes that subjects call upon during
      their everyday lives. Naturalistic approaches thus provide an important adjunct
      to traditional laboratory-based studies. For example, wearable self-contained
      tracking systems can allow subjects to be monitored outside the laboratory, where
      they engage spontaneously in natural everyday behavior. Similarly, advances in
      virtual reality technology allow laboratory-based tasks to be made more
      naturalistic. Here, we review naturalistic approaches, including perspectives
      from psychology and visual neuroscience, as well as studies and technological
      advances in the field of sensorimotor control.

PMID- 21741542
TI  - Sensory change following motor learning.
AB  - Here we describe two studies linking perceptual change with motor learning. In
      the first, we document persistent changes in somatosensory perception that occur
      following force field learning. Subjects learned to control a robotic device that
      applied forces to the hand during arm movements. This led to a change in the
      sensed position of the limb that lasted at least 24 h. Control experiments
      revealed that the sensory change depended on motor learning. In the second study,
      we describe changes in the perception of speech sounds that occur following
      speech motor learning. Subjects adapted control of speech movements to compensate
      for loads applied to the jaw by a robot. Perception of speech sounds was measured
      before and after motor learning. Adapted subjects showed a consistent shift in
      perception. In contrast, no consistent shift was seen in control subjects and
      subjects that did not adapt to the load. These studies suggest that motor
      learning changes both sensory and motor function.

PMID- 21741543
TI  - Sensory motor remapping of space in human-machine interfaces.
AB  - Studies of adaptation to patterns of deterministic forces have revealed the
      ability of the motor control system to form and use predictive representations of
      the environment. These studies have also pointed out that adaptation to novel
      dynamics is aimed at preserving the trajectories of a controlled endpoint, either
      the hand of a subject or a transported object. We review some of these
      experiments and present more recent studies aimed at understanding how the motor
      system forms representations of the physical space in which actions take place.
      An extensive line of investigations in visual information processing has dealt
      with the issue of how the Euclidean properties of space are recovered from visual
      signals that do not appear to possess these properties. The same question is
      addressed here in the context of motor behavior and motor learning by observing
      how people remap hand gestures and body motions that control the state of an
      external device. We present some theoretical considerations and experimental
      evidence about the ability of the nervous system to create novel patterns of
      coordination that are consistent with the representation of extrapersonal space.
      We also discuss the perspective of endowing human-machine interfaces with
      learning algorithms that, combined with human learning, may facilitate the
      control of powered wheelchairs and other assistive devices.

PMID- 21741544
TI  - Locomotor adaptation.
AB  - Motor learning is an essential part of human behavior, but poorly understood in
      the context of walking control. Here, we discuss our recent work on locomotor
      adaptation, which is an error driven motor learning process used to alter
      spatiotemporal elements of walking. Locomotor adaptation can be induced using a
      split-belt treadmill that controls the speed of each leg independently.
      Practicing split-belt walking changes the coordination between the legs,
      resulting in storage of a new walking pattern. Here, we review findings from this
      experimental paradigm regarding the learning and generalization of locomotor
      adaptation. First, we discuss how split-belt walking adaptation develops slowly
      throughout childhood and adolescence. Second, we demonstrate that conscious
      effort to change the walking pattern during split-belt training can speed up
      adaptation but worsens retention. In contrast, distraction (i.e., performing a
      dual task) during training slows adaptation but improves retention. Finally, we
      show the walking pattern acquired on the split-belt treadmill generalizes to
      natural walking when vision is removed. This suggests that treadmill learning can
      be generalized to different contexts if visual cues specific to the treadmill are
      removed. These findings allow us to highlight the many future questions that will
      need to be answered in order to develop more rational methods of rehabilitation
      for walking deficits.

PMID- 21741545
TI  - Age-related changes in the cognitive function of sleep.
AB  - Healthy aging is characterized by a diminished quality of sleep with decreased
      sleep duration and increased time awake after sleep onset. Older adults awaken
      more frequently and tend to awaken less from rapid eye movement (REM) sleep and
      more from non-REM (nREM) sleep than young adults. Sleep architecture also begins
      changing in middle age leading to a dramatic decrease in the deepest stage of
      nREM-slow wave sleep (SWS)-as aging progresses. Other less marked nREM changes
      include reduced numbers of sleep spindles and K-complexes. In contrast, the
      amount of REM diminishes only slightly. Both circadian and homeostatic sleep
      regulatory processes are affected by aging. Circadian rhythms of temperature,
      melatonin, and cortisol are phase advanced and their amplitude diminished. An
      increased number of nocturnal awakenings and diminished daytime sleepiness
      suggest diminished homeostatic sleep pressure. A variety of endocrine and
      neuromodulatory changes (e.g., reduced growth hormone and dopamine levels) also
      accompany healthy aging. Healthy aging is characterized by declines in working
      memory and new episodic memory performance with relative sparing of semantic
      memory, recognition memory, and priming. Memory systems impacted by aging are
      associated with volumetric and functional changes in fronto-striatal circuits
      along with more limited changes in medial temporal structures (in which larger
      aging-related changes suggest neuropathology). Cross-sectional studies generally
      associate poorer sleep quality with poorer neuropsychological functioning.
      However, paradoxically, older adults appear to be more resistant to the cognitive
      effects of sleep deprivation, restriction, and fragmentation than younger adults.
      A new and expanding field examines the interaction between aging and sleep
      dependent memory consolidation. Among forms of learning displaying prominent
      sleep-dependent consolidation in young adults, motor-sequence learning displays
      loss of sleep-dependent consolidation with aging whereas sleep-dependent
      consolidation of verbal declarative memory appears spared. Findings suggest that
      improving sleep through behavioral or pharmacological treatments may enhance
      cognition and performance in older adults.

PMID- 21741546
TI  - Motor adaptation and proprioceptive recalibration.
AB  - Goal-directed reaches are rapidly adapted after reaching with misaligned visual
      feedback of the hand. It has been suggested that reaching with misaligned visual
      feedback of the hand also results in proprioceptive recalibration (i.e.,
      realigning proprioceptive estimates of hand position to match visual estimates).
      In this chapter, we review a series of experiments conducted in our lab which
      examine this proposal. We assessed proprioceptive recalibration by comparing
      subjects' estimates of the position at which they felt their hand was aligned
      with a reference marker (visual or proprioceptive) before and after aiming with a
      misaligned cursor that was typically rotated 30 degrees  clockwise (CW) with
      respect to the hand. In general, results indicated that subjects recalibrated
      proprioception such that their estimates of felt hand position were shifted in
      the same direction that they adapted their reaches. Moreover, proprioception was
      recalibrated to a similar extent of motor adaptation (~30%), regardless of how
      the hand was positioned during the estimate trials (active or passive placement),
      the location or modality of the reference marker (visual or proprioceptive), the
      hand used during reach training (right or left), how the distortion was
      introduced (gradual or abrupt), and age (young or older subjects) and the
      magnitude of the visuomotor distortion introduced (30 degrees  or 50 degrees  or
      70 degrees ). These results suggest that in addition to recalibrating the
      sensorimotor transformations underlying reaching movements, visuomotor adaptation
      results in partial proprioceptive recalibration.

PMID- 21741547
TI  - Perception and action in singing.
AB  - Singing is an important cultural activity, yet many people are hesitant to sing,
      because they feel they do not sing well. This chapter reviews the work that has
      been done concerning singing among nonmusicians, focusing on pitch accuracy,
      which is one of the most important aspects of singing. First, we look at the
      prevalence of poor pitch singing and examine what it means to be a poor singer.
      Next, we look at the possible causes of poor singing and examine the possible
      roles of perceptual deficits, sensorimotor translation deficits, motor control
      deficits, and feedback deficits. Whereas many previous studies have tried to
      explain poor singing by positing perceptual problems, we argue that the current
      evidence supports sensorimotor translation deficits and motor control deficits as
      the more likely causes. Finally, we examine the neural bases of singing and the
      possibility of a dual-pathway basis for pitch perception and production. Based on
      these studies, we suggest changes to improve the singing abilities of poor
      singers.

PMID- 21741548
TI  - Lifelong plasticity in the rat auditory cortex: basic mechanisms and role of
      sensory experience.
AB  - The rodent auditory cortex has provided a particularly useful model for studying
      cortical plasticity phenomenology and mechanisms, both in infant and in adult
      animal models. Much of our initial understanding of the neurological processes
      underlying learning-induced changes in the cortex stems from the early
      exploitation of this model. More recent studies have provided a rich and
      elaborate demonstration of the "rules" governing representational plasticity
      induced during the critical period (CP) and in the longer post-CP "adult"
      plasticity epoch. These studies have also contributed importantly to the
      application of these "rules" to the development of practical training tools
      designed to improve the functional capacities of the auditory, language, and
      reading capacities of both children with developmental impairments and adults
      with acquired impairments in the auditory/aural speed and related cognitive
      domains. Using age as a connecting thread, we review recent studies performed in
      the rat primary auditory cortex (A1) that have provided further insight into the
      role of sensory experience in the shaping auditory signal representations, and
      into their possible role in shaping the machinery that regulates "adult"
      plasticity in A1. With this background, the role of auditory training in the
      remediation of auditory processing impairments is briefly discussed.

PMID- 21741549
TI  - Enhancing visual cues to orientation: suggestions for space travelers and the
      elderly.
AB  - Establishing our orientation in the world is necessary for almost all aspects of
      perception and behavior. Gravity usually defines the critical reference
      direction. The direction of gravity is sensed by somatosensory detectors
      indicating pressure points and specialized organs in the vestibular system and
      viscera that indicate gravity's physical pull. However, gravity's direction can
      also be sensed visually since we see the effects of gravity on static and moving
      objects and also deduce its direction from the global structure of a scene
      indicated by features such as the sky and ground. When cues from either visual or
      physical sources are compromised or ambiguous, perceptual disorientation may
      result, often with a tendency to replace gravity with the body's long axis as a
      reference. Orientation cues are compromised while floating in the weightlessness
      of space (which neutralizes vestibular and somatosensory cues) or while suspended
      at neutral buoyancy in the ocean (which neutralizes somatosensory cues) and the
      ability to sense orientation cues may also be compromised in the elderly or in
      clinical populations. In these situations, enhancing the visual cues to
      orientation may be beneficial. In this chapter, we review research using
      specially constructed virtual and real environments to quantify the contribution
      of various visual orientation cues. We demonstrate how visual cues can counteract
      disorientation by providing effective orientation information.

PMID- 21741550
TI  - Organization and plasticity in multisensory integration: early and late
      experience affects its governing principles.
AB  - Neurons in the midbrain superior colliculus (SC) have the ability to integrate
      information from different senses to profoundly increase their sensitivity to
      external events. This not only enhances an organism's ability to detect and
      localize these events, but to program appropriate motor responses to them. The
      survival value of this process of multisensory integration is self-evident, and
      its physiological and behavioral manifestations have been studied extensively in
      adult and developing cats and monkeys. These studies have revealed, that contrary
      to expectations based on some developmental theories this process is not present
      in the newborn's brain. The data show that is acquired only gradually during
      postnatal life as a consequence of at least two factors: the maturation of
      cooperative interactions between association cortex and the SC, and extensive
      experience with cross-modal cues. Using these factors, the brain is able to craft
      the underlying neural circuits and the fundamental principles that govern
      multisensory integration so that they are adapted to the ecological circumstances
      in which they will be used.

PMID- 21741551
TI  - Multisensory object representation: insights from studies of vision and touch.
AB  - Behavioral studies show that the unisensory representations underlying within
      modal visual and haptic object recognition are strikingly similar in terms of
      view- and size-sensitivity, and integration of structural and surface properties.
      However, the basis for these attributes differs in each modality, indicating that
      while these representations are functionally similar, they are not identical.
      Imaging studies reveal bisensory, visuo-haptic object selectivity, notably in the
      lateral occipital complex and the intraparietal sulcus, that suggests a shared
      representation of objects. Such a multisensory representation could underlie
      visuo-haptic cross-modal object recognition. In this chapter, we compare visual
      and haptic within-modal object recognition and trace a progression from
      functionally similar but separate unisensory representations to a shared
      multisensory representation underlying cross-modal object recognition as well as
      view-independence, regardless of modality. We outline, and provide evidence for,
      a model of multisensory object recognition in which representations are flexibly
      accessible via top-down or bottom-up processing, the choice of route being
      influenced by object familiarity and individual preference along the object
      spatial continuum of mental imagery.

PMID- 21741552
TI  - Adaptation and maladaptation insights from brain plasticity.
AB  - Evolutionary concepts such as adaptation and maladaptation have been used by
      neuroscientists to explain brain properties and mechanisms. In particular, one of
      the most compelling characteristics of the brain, known as neuroplasticity,
      denotes the ability of the brain to continuously adapt its functional and
      structural organization to changing requirements. Although brain plasticity has
      evolved to favor adaptation, there are cases in which the same mechanisms
      underlying adaptive plasticity can turn into maladaptive changes. Here, we will
      consider brain plasticity and its functional and structural consequences from an
      evolutionary perspective, discussing cases of adaptive and maladaptive plasticity
      and using examples from typical and atypical development.

PMID- 21741553
TI  - Sensory integration for reaching: models of optimality in the context of behavior
      and the underlying neural circuits.
AB  - Although multisensory integration has been well modeled at the behavioral level,
      the link between these behavioral models and the underlying neural circuits is
      still not clear. This gap is even greater for the problem of sensory integration
      during movement planning and execution. The difficulty lies in applying simple
      models of sensory integration to the complex computations that are required for
      movement control and to the large networks of brain areas that perform these
      computations. Here I review psychophysical, computational, and physiological work
      on multisensory integration during movement planning, with an emphasis on goal
      directed reaching. I argue that sensory transformations must play a central role
      in any modeling effort. In particular, the statistical properties of these
      transformations factor heavily into the way in which downstream signals are
      combined. As a result, our models of optimal integration are only expected to
      apply "locally," that is, independently for each brain area. I suggest that local
      optimality can be reconciled with globally optimal behavior if one views the
      collection of parietal sensorimotor areas not as a set of task-specific domains,
      but rather as a palette of complex, sensorimotor representations that are
      flexibly combined to drive downstream activity and behavior.

PMID- 21741554
TI  - Sensory rehabilitation in the plastic brain.
AB  - The purpose of this review is to consider new sensory rehabilitation avenues in
      the context of the brain's remarkable ability to reorganize itself following
      sensory deprivation. Here, deafness and blindness are taken as two illustrative
      models. Mainly, two promising rehabilitative strategies based on opposing
      theoretical principles will be considered: sensory substitution and
      neuroprostheses. Sensory substitution makes use of the remaining intact senses to
      provide blind or deaf individuals with coded information of the lost sensory
      system. This technique thus benefits from added neural resources in the
      processing of the remaining senses resulting from crossmodal plasticity, which is
      thought to be coupled with behavioral enhancements in the intact senses. On the
      other hand, neuroprostheses represent an invasive approach aimed at stimulating
      the deprived sensory system directly in order to restore, at least partially, its
      functioning. This technique therefore relies on the neuronal integrity of the
      brain areas normally dedicated to the deprived sense and is rather hindered by
      the compensatory reorganization observed in the deprived cortex. Here, we stress
      that our understanding of the neuroplastic changes that occur in sensory-deprived
      individuals may help guide the design and the implementation of such
      rehabilitative methods.

PMID- 21741555
TI  - Crossmodal plasticity in sensory loss.
AB  - In this review, we describe crossmodal plasticity following sensory loss in three
      parts, with each section focusing on one sensory system. We summarize a wide
      range of studies showing that sensory loss may lead, depending of the affected
      sensory system, to functional changes in other, primarily not affected senses,
      which range from heightened to lowered abilities. In the first part, the effects
      of blindness on mainly audition and touch are described. The latest findings on
      brain reorganization in blindness are reported, with a particular emphasis on
      imaging studies illustrating how nonvisual inputs recruit the visually
      deafferented occipital cortex. The second part covers crossmodal processing in
      deafness, with a special focus on the effects of deafness on visual processing.
      In the last portion of this review, we present the effects that the loss of a
      chemical sense have on the sensitivity of the other chemical senses, that is,
      smell, taste, and trigeminal chemosensation. We outline how the convergence of
      the chemical senses to the same central processing areas may lead to the observed
      reduction in sensitivity of the primarily not affected senses. Altogether, the
      studies reviewed herein illustrate the fascinating plasticity of the brain when
      coping with sensory deprivation.

PMID- 21741556
TI  - Adaptive crossmodal plasticity in deaf auditory cortex: areal and laminar
      contributions to supranormal vision in the deaf.
AB  - This chapter is a summary of three interdigitated investigations to identify the
      neural substrate underlying supranormal vision in the congenitally deaf. In the
      first study, we tested both congenitally deaf and hearing cats on a battery of
      visual psychophysical tasks to identify those visual functions that are enhanced
      in the congenitally deaf. From this investigation, we found that congenitally
      deaf, compared to hearing, cats have superior visual localization in the
      peripheral field and lower visual movement detection thresholds. In the second
      study, we examined the role of "deaf" auditory cortex in mediating the
      supranormal visual abilities by reversibly deactivating specific cortical loci
      with cooling. We identified that in deaf cats, reversible deactivation of a
      region of cortex typically identified as the posterior auditory field (PAF) in
      hearing cats selectively eliminated superior visual localization abilities. It
      was also found that deactivation of the dorsal zone (DZ) of "auditory" cortex
      eliminated the superior visual motion detection abilities of deaf cats. In the
      third study, graded cooling was applied to deaf PAF and deaf DZ to examine the
      laminar contributions to the superior visual abilities of the deaf. Graded
      cooling of deaf PAF revealed that deactivation of the superficial layers alone
      does not cause significant visual localization deficits. Profound deficits were
      identified only when cooling extended through all six layers of deaf PAF. In
      contrast, graded cooling of deaf DZ showed that deactivation of only the
      superficial layers was required to elicit increased visual motion detection
      thresholds. Collectively, these three studies show that the superficial layers of
      deaf DZ mediate the enhanced visual motion detection of the deaf, while the full
      thickness of deaf PAF must be deactivated in order to eliminate the superior
      visual localization abilities of the congenitally deaf. Taken together, this
      combination of experimental approaches has demonstrated a causal link between the
      crossmodal reorganization of auditory cortex and enhanced visual abilities of the
      deaf, as well as identified the cortical regions responsible for adaptive
      supranormal vision.

PMID- 21741557
TI  - The wonder of you....

PMID- 21741558
TI  - And the survey says....

PMID- 21741559
TI  - Is a back to basics approach to medication error reduction enough?

PMID- 21741560
TI  - Response to JEN Article, "Health Care Providers' Evaluations of Family Presence
      During Resuscitation".

PMID- 21741563
TI  - Resuscitation medication delivery in pediatric patients.

PMID- 21741565
TI  - Geriatric emergency nurses: addressing the needs of an aging population.
AB  - INTRODUCTION: Older adults account for up to 14.5% of ED visits. Presentation of
      older adults can differ from younger adults. Emergency visits by older adults
      that are characterized by comorbidity, cognitive and functional impairment, and
      complex social issues. In addition, older adults present with subtle, atypical
      symptoms making diagnosis and discharge more challenging. The purpose of this
      study was to describe an innovative geriatric emergency nurse role that has been
      implemented to address the unique needs of older adults in the emergency
      department. METHODS: This was an exploratory, descriptive study. The study sample
      was comprised of two groups: Geriatric Emergency Nurses (N=5) and key informants
      (N=15). The study was based at a tertiary hospital in Vancouver, Canada. Data was
      collected using semi-structured interviews. Data were analyzed using thematic
      analysis. RESULTS: The findings are organized into three sections: defining the
      role and its functions; a collaborative relationship: fitting in to the larger
      emergency department; and recommendations for future role development.
      CONCLUSION: Findings from the study have led to further considerations about the
      role in relation to communication about older patients both within the emergency
      department and with community stakeholders. We also discuss the importance of
      this role in relation to the continuum of care and recognizing the central role
      of the emergency department as a place for intervention. Lastly, we consider the
      need for further integration of gerontological knowledge and expertise within the
      emergency department beyond a specialized role.

PMID- 21741566
TI  - The impact of time from ED arrival to surgery on mortality and hospital length of
      stay in patients with traumatic brain injury.
AB  - INTRODUCTION: The previous studies examining the benefits of timely surgery in
      patients with traumatic brain injury (TBI) have yielded inconsistent conclusions.
      This study examined how time from ED arrival to surgery in patients with TBI
      influenced two patient outcomes: hospital mortality and length of hospital stay.
      METHODS: Using a multivariate and cross-sectional research design, the study
      sample included 493 patients from the 17 level I and II trauma centers that met
      inclusion criteria in the National Trauma Data Bank 4.0. The patient
      characteristics (eg, age, Glasgow Coma Scale score, Injury Severity score, and ED
      arrival time) and trauma center characteristics (eg, ownership, designation type,
      and center level) were examined. Student t test, chi2 test, analysis of variance,
      and multilevel regression models were used to analyze data. RESULTS: Patients who
      underwent craniotomy or drainage of hematoma within 4 hours of arrival had half
      the likelihood of mortality when compared with those who underwent surgery more
      than 4 hours after ED arrival (odds ratio = .49; 95% confidence interval = .24 to
      .99). When patients had surgery within 4 hours of arrival, they had a
      significantly shorter length of hospital stay than did patients who had surgery
      more than 4 hours after arrival in the emergency department (Estimate = -.10, 95%
      confidence interval = -.19 to -.01). DISCUSSION: Based on the results of this
      study using a large sample from multiple centers and advanced statistics,
      benefits of early clinical assessment and quick access to neurosurgical surgery
      are substantiated in patients with TBI.

PMID- 21741567
TI  - Characteristics of patients who leave the ED triage area without being seen by a
      doctor: a descriptive study in an urban level II Italian University Hospital.
AB  - OBJECTIVE: In this paper, we describe demographic and clinical features of
      patients who left the triage area before the visit in the emergency department of
      Azienda Ospedaliera Universitaria Careggi in 2006. METHODS: This is a descriptive
      retrospective study. Data was collected from electronic medical charts. RESULTS:
      We recorded 45,019 patients who arrived in the emergency department. Of those,
      904 left without being seen (2%; Male 51.5%; Female 48.2%). The mean age was 41
      years (median 37; range 14-95). We found that this was more common during June
      and July (114 and 107 cases) and on Mondays (20.5%), with lower rates on
      Saturdays and Sundays (11.3% and 9%). Two-hundred thirty-nine patients were not
      Italian. Patients' waiting times before leaving without being seen collected from
      the nursing notes were recorded in 457 cases (50.5%), and showed a median of 70
      minutes (range 0-386). There was a significant difference between this value and
      the median of waiting times (95 minutes) calculated from the ending time of
      medical charts in the same group of patients (Wilcoxon Signed Rank Test - P <
      0.0001). It confirms the hypothesis that the patients' length of stay before
      leaving the triage area, gathered from medical charts, isn't reliable because of
      the delayed ending of charts. After 72 hours from the leave, 17 patients
      returned. The outcome were: 2 admissions in general ward and 6 new cases of
      leaving without being seen. CONCLUSIONS: There was a prevalence of low-priority
      triage-level patients compared to the general ED case mix. The rate of patients'
      leaves follows the indications of Tuscany Region (patients' leaves <5% total ED
      population).

PMID- 21741568
TI  - Sickle cell disease management in the emergency department: what every emergency
      nurse should know.

PMID- 21741569
TI  - Pain recidivists in the emergency department.

PMID- 21741570
TI  - A 69-year-old man with gastrointestinal exsanguination.

PMID- 21741572
TI  - The "ED Mini": a novel approach to clinical education.

PMID- 21741573
TI  - Implementing the IOM recommendations for Improving Pediatric Emergency Care in
      your Emergency Department: start from where you are!

PMID- 21741574
TI  - Epinephrine in ventricular fibrillation: friend or foe? A review for the
      Emergency Nurse.

PMID- 21741575
TI  - The detection of 3 leptin receptor isoforms in crucian carp gill and the
      influence of fasting and hypoxia on their expression.
AB  - To understand leptin signaling pathway in the crucian carp (Carassius carassius),
      we cloned 3 leptin receptor isoform complementary DNAs (ie, the long form [cclpr
      L], the short form [cclpr-s1], and the secreted form [cclpr-s2]). Variant cclpr-L
      had a 3,255-bp open reading frame and a complete intracellular domain with box 1
      and box 2 consensus sequences. By contrast, cclpr-s1 contained only 4 amino acids
      in its intracellular domain, without the "box 1" motif, which is conserved among
      membrane-bound leptin receptor short isoforms in mammals. Variant cclpr-s2 had no
      transmembrane domain, suggesting that it is a soluble form of the receptor, and
      alternative splicing of cclpr-s2 mRNA employs a different mechanism for the
      generation of soluble leptin receptor by intron retention. The fasting-treated
      fish showed significantly lower cclpr-L mRNA levels in gill tissue than the
      control group, whereas cclpr-s2 mRNA levels did not vary significantly among the
      groups. Treatment with hypoxia significantly increased mRNA levels of both cclpr
      L and cclpr-s2 in gill tissue. To our knowledge, this is the first study of
      leptin receptor isoforms expression in teleosts.

PMID- 21741576
TI  - Evaluation of commercially available assays for the measurement of equine
      insulin.
AB  - Determining circulating equine insulin concentrations is becoming increasingly
      important in equine clinical practice and research. Most available assays are
      optimized for human medicine, but there is strong equine cross-reactivity because
      of the highly conserved nature of insulin. To identify an accurate and reliable
      assay for equine insulin, 6 commercial immunoassays were evaluated for precision,
      accuracy, and specificity. Only 1 assay initially reached the requisite standard:
      Mercodia Equine Insulin Enzyme-linked Immunosorbent assay (ELISA). Plasma matrix
      interferences were identified when the provided assay buffer was used with the
      Siemens Count-a-Coat Insulin radioimmunoassay (RIA) but not when charcoal
      stripped equine plasma was used as the diluent. This modified RIA and the
      Mercodia Equine Insulin ELISA were evaluated further by directly examining
      accuracy by comparing their results for 18 equine plasma samples with values
      obtained using liquid chromatography and high-resolution/high-accuracy mass
      spectrometry (LC-MS). Compared with LC-MS measurements, the modified Siemens
      Insulin RIA rendered a moderate Lin's concordance coefficient (rho(c)) of 0.41,
      whereas the Mercodia Equine Insulin ELISA rendered a very poor rho(c) of 0.06.
      This suggests that the Siemens Insulin RIA is appropriate to use for routine
      evaluations when LC-MS is not available.

PMID- 21741577
TI  - Pharmacological characterization of canine melancortin-4 receptor and its natural
      variant V213F.
AB  - Dogs have become one of the most important companion animals in modern society.
      However, it is estimated that 20% to 40% of owned dogs are obese, suggesting that
      obesity has become one of the most important canine health problem. In addition,
      obesity in dogs also leads to type II diabetes. Because the melanocortin-4
      receptor (MC4R) has been shown to be essential in maintaining energy homeostasis
      in several different species, including rodents and humans, we initiated studies
      toward elucidating the roles of MC4R in obesity pathogenesis in dogs. Canine MC4R
      has been cloned, and a missense variant V213F was identified. We designed primers
      and successfully cloned canine MC4R and generated the variant V213F by site
      directed mutagenesis. The objective of this study was to investigate the
      pharmacological properties of canine MC4R and its natural variant V213F. We
      measured ligand binding and signaling properties with the use of both natural and
      synthetic ligands. Human MC4R was also included in the experiments for
      comparison. Both wild-type canine MC4R and its natural variant V213F functioned
      normally in terms of binding and signaling. Of the ligands we used, [Nle(4), D
      Phe(7)]-alpha-melanocyte-stimulating hormone is the most potent ligand. We
      conclude that the cloned canine MC4R is a functional receptor, and the natural
      variant V213F does not have any functional defect and therefore is not likely to
      cause obesity in dogs.

PMID- 21741578
TI  - Effect of dose of estradiol-17beta on prominence of an induced 13,14-dihydro-15
      keto-PGF(2alpha) (PGFM) pulse and relationship of prominence to progesterone, LH,
      and luteal blood flow in heifers.
AB  - Various doses of estradiol-17beta (E(2)) were used in heifers to induce a pulse
      of 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM). The effect of E(2)
      concentration on the prominence of PGFM pulses and the relationship between
      prominence and intrapulse concentration of progesterone (P(4)), LH, and luteal
      blood flow were studied. A single dose of 0 (vehicle), 0.01, 0.05, or 0.1 mg of
      E(2) was given (n = six/group) 14 d after ovulation. Blood samples were
      collected, and luteal blood flow was evaluated hourly for 10 h after the
      treatment. The 0.05-mg dose increased and the 0.1-mg dose further increased the
      prominence of the induced PGFM pulse, compared with the 0.0-mg dose and the 0.01
      mg dose. The PGFM pulses were subdivided into three different prominence
      categories (<50, 50 to 150, and >150 pg/mL at the peak). In the 50 to 150
      category, P(4) concentration increased (P < 0.05) between -2 h and 0 h (0 h =
      peak of PGFM pulse). In the >150 category, P(4) decreased (P < 0.05) between -1 h
      and 0 h, LH increased (P < 0.05) at 1 h, and luteal blood flow apparently
      decreased (P < 0.05) at 2 h of the PGFM pulse. The novel results supported the
      following hypotheses: (1) an increase in E(2) concentration increases the
      prominence of a PGFM pulse, and (2) greater prominence of a PGFM pulse is
      associated with a greater transient intrapulse depression of P(4) at the peak of
      the PGFM pulse. In addition, the extent of the effect of prostaglandin F(2alpha)
      on the increase in LH and changes in blood flow within the hours of a PGFM pulse
      was related positively to the prominence of the PGFM pulse.

PMID- 21741579
TI  - Houses made by protists.

PMID- 21741580
TI  - Toll-like receptors.

PMID- 21741581
TI  - Learning to reach for 'invisible' visual input.

PMID- 21741582
TI  - Asexuality: the insects that stick with it.
AB  - One hope of trying to understand why sex is so powerful and prevalent a mode of
      reproduction relies on the rare examples of animals that persist long-term
      without having sex. Now, several species of stick insects join that illustrious
      circle.

PMID- 21741583
TI  - Basal ganglia: insights into origins from lamprey brains.
AB  - The lamprey brain has now been shown to have basal ganglia circuitry, with an
      output that acts tonically on midbrain and brainstem motor centers and is
      modulated by ascending dopaminergic input. This condition was believed to
      represent the tetrapod condition, but now appears to be far more ancient.

PMID- 21741584
TI  - Phagocytes: fussy about carbs.
AB  - A new mechanistic model based on the formation of a phagocytic synapse explains
      how immune cells detect and respond to direct contact with fungal pathogens.

PMID- 21741585
TI  - Phyllotaxis: in search of the golden angle.
AB  - How are the regular patterns of organs established along a plant stem and how are
      the transitions between different patterns regulated? Now genes of the PLETHORA
      family have been shown to modulate these transitions by fine-tuning the
      mechanisms of polar transport of auxin, a key effector of organogenesis.

PMID- 21741586
TI  - Olfactory coding: giant inhibitory neuron governs sparse odor codes.
AB  - Electrophysiological investigations in locusts have revealed that the sparseness
      of odor representations, in the brain region expected to mediate olfactory
      learning, is shaped by a unique inhibitory neuron.

PMID- 21741587
TI  - Vesicle transport: springing the TRAPP.
AB  - When a coated transport vesicle docks with its target membrane, the coat proteins
      and docking machinery must be released before the membranes can fuse. A recent
      paper shows how this disassembly is triggered at precisely the right time.

PMID- 21741588
TI  - Animal cooperation: keeping a clean(ing) reputation.
AB  - Cleaner wrasses are a model for the study of animal cooperation. Prospective
      clients can observe whether the cleaner works faithfully, and cleaners being
      watched remove just parasites while those that are not, nip the client for a
      tastier snack.

PMID- 21741589
TI  - Apiology: royal secrets in the queen's fat body.
AB  - Royalactin, a component of royal jelly, induces queen differentiation in
      honeybees. Surprisingly, royalactin has a similar effect on growth in fruit
      flies, highlighting many unexpected features of growth regulation by the insect
      fat tissue.

PMID- 21741590
TI  - New moves in motor control.
AB  - Motor behaviour results from information processing across multiple neural
      networks acting at all levels from initial selection of the behaviour to its
      final generation. Understanding how motor behaviour is produced requires
      identifying the constituent neurons of these networks, their cellular properties,
      and their pattern of synaptic connectivity. Neural networks have been
      traditionally studied with neurophysiological and neuroanatomical approaches.
      These approaches have been highly successful in particularly suitable 'model'
      preparations, typically ones in which the numbers of neurons in the networks were
      relatively small, neural network composition was unvarying across individual
      animals, and the preparations continued to produce fictive motor patterns in
      vitro. However, analysing networks without these characteristics, and analysing
      the complete ensemble of networks that cooperatively generate behaviours, is
      difficult with these approaches. Recently developed molecular and neurogenetic
      tools provide additional avenues for analysing motor networks by allowing
      individual or groups of neurons within networks to be manipulated in novel ways
      and allowing experiments to be performed not only in vitro but also in vivo. We
      review here some of the new insights into motor network function that these
      advances have provided and indicate how these advances might bridge gaps in our
      understanding of motor control. To these ends, we first review motor neural
      network organisation highlighting cross-phylum principles. We then use prominent
      examples from the field to show how neurogenetic approaches can complement
      classical physiological studies, and identify additional areas where these
      approaches could be advantageously applied.

PMID- 21741591
TI  - The role of TET2 in hematologic neoplasms.
AB  - TET2 encodes an enzyme that hydroxylates methylcytosine and is frequently
      targeted by loss-of-function mutations in myelodysplasia, myeloproliferative
      disorders, and acute myeloid leukemia. In this issue of Cancer Cell, two studies
      show that inactivation of Tet2 enhances hematopoietic stem cell self renewal and
      promotes the development of myeloproliferative disorders.

PMID- 21741592
TI  - BCL6: a novel target for therapy of Ph+ B cell acute lymphoblastic leukemia.
AB  - BCL6 is a zinc-finger transcriptional repressor known for its oncogenic role in B
      cell lymphoma. In a recent issue of Nature, Duy et al. describe a novel role for
      BCL6 at the center of a transcriptional network in Ph(+) acute lymphoblastic
      leukemia cells that modulates their leukemogenicity and response to kinase
      inhibitors.

PMID- 21741593
TI  - Comprehensive identification of somatic mutations in chronic lymphocytic
      leukemia.
AB  - Massively parallel sequencing enables the sequencing of whole genomes, exomes,
      and transcriptomes from many tumor samples. Thus, it now is possible to
      comprehensively identify somatic mutations, including single base changes,
      deletions, insertions, and genomic rearrangements. Early results for
      hematopoietic tumors show great promise, but many questions remain to be
      answered.

PMID- 21741594
TI  - Beefing up prostate cancer therapy with performance-enhancing (anti-) steroids.
AB  - In the May 26th issue of the New England Journal of Medicine, de Bono et al.
      report that the inhibition of androgen synthesis by abiraterone acetate prolonged
      the survival of men with prostate cancer previously treated by androgen
      suppression.

PMID- 21741595
TI  - Cell of origin in AML: susceptibility to MN1-induced transformation is regulated
      by the MEIS1/AbdB-like HOX protein complex.
AB  - Pathways defining susceptibility of normal cells to oncogenic transformation may
      be valuable therapeutic targets. We characterized the cell of origin and its
      critical pathways in MN1-induced leukemias. Common myeloid (CMP) but not
      granulocyte-macrophage progenitors (GMP) could be transformed by MN1.
      Complementation studies of CMP-signature genes in GMPs demonstrated that MN1
      leukemogenicity required the MEIS1/AbdB-like HOX-protein complex. ChIP-sequencing
      identified common target genes of MN1 and MEIS1 and demonstrated identical
      binding sites for a large proportion of their chromatin targets. Transcriptional
      repression of MEIS1 targets in established MN1 leukemias demonstrated
      antileukemic activity. As MN1 relies on but cannot activate expression of
      MEIS1/AbdB-like HOX proteins, transcriptional activity of these genes determines
      cellular susceptibility to MN1-induced transformation and may represent a
      promising therapeutic target.

PMID- 21741596
TI  - Selective killing of mixed lineage leukemia cells by a potent small-molecule
      DOT1L inhibitor.
AB  - Mislocated enzymatic activity of DOT1L has been proposed as a driver of
      leukemogenesis in mixed lineage leukemia (MLL). The characterization of
      EPZ004777, a potent, selective inhibitor of DOT1L is reported. Treatment of MLL
      cells with the compound selectively inhibits H3K79 methylation and blocks
      expression of leukemogenic genes. Exposure of leukemic cells to EPZ004777 results
      in selective killing of those cells bearing the MLL gene translocation, with
      little effect on non-MLL-translocated cells. Finally, in vivo administration of
      EPZ004777 leads to extension of survival in a mouse MLL xenograft model. These
      results provide compelling support for DOT1L inhibition as a basis for targeted
      therapeutics against MLL.

PMID- 21741597
TI  - MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L.
AB  - The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in
      the development of leukemias bearing translocations of the Mixed Lineage Leukemia
      (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model,
      and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3
      in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal
      profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of
      Dot1l led to downregulation of direct MLL-AF9 targets and an MLL translocation
      associated gene expression signature, whereas global gene expression remained
      largely unaffected. Suppression of MLL translocation-associated gene expression
      corresponded with dependence of MLL-AF9 leukemia on Dot1l in vivo. These data
      point to DOT1L as a potential therapeutic target in MLL-rearranged leukemia.

PMID- 21741598
TI  - A Pin1/mutant p53 axis promotes aggressiveness in breast cancer.
AB  - TP53 missense mutations dramatically influence tumor progression, however, their
      mechanism of action is still poorly understood. Here we demonstrate the
      fundamental role of the prolyl isomerase Pin1 in mutant p53 oncogenic functions.
      Pin1 enhances tumorigenesis in a Li-Fraumeni mouse model and cooperates with
      mutant p53 in Ras-dependent transformation. In breast cancer cells, Pin1 promotes
      mutant p53 dependent inhibition of the antimetastatic factor p63 and induction of
      a mutant p53 transcriptional program to increase aggressiveness. Furthermore, we
      identified a transcriptional signature associated with poor prognosis in breast
      cancer and, in a cohort of patients, Pin1 overexpression influenced the
      prognostic value of p53 mutation. These results define a Pin1/mutant p53 axis
      that conveys oncogenic signals to promote aggressiveness in human cancers.

PMID- 21741599
TI  - Proinvasion metastasis drivers in early-stage melanoma are oncogenes.
AB  - Clinical and genomic evidence suggests that the metastatic potential of a primary
      tumor may be dictated by prometastatic events that have additional oncogenic
      capability. To test this "deterministic" hypothesis, we adopted a comparative
      oncogenomics-guided function-based strategy involving: (1) comparison of global
      transcriptomes of two genetically engineered mouse models with contrasting
      metastatic potential, (2) genomic and transcriptomic profiles of human melanoma,
      (3) functional genetic screen for enhancers of cell invasion, and (4) evidence of
      expression selection in human melanoma tissues. This integrated effort identified
      six genes that are potently proinvasive and oncogenic. Furthermore, we show that
      one such gene, ACP5, confers spontaneous metastasis in vivo, engages a key
      pathway governing metastasis, and is prognostic in human primary melanomas.

PMID- 21741600
TI  - miR-30b/30d regulation of GalNAc transferases enhances invasion and
      immunosuppression during metastasis.
AB  - To metastasize, a tumor cell must acquire abilities such as the capacity to
      colonize new tissue and evade immune surveillance. Recent evidence suggests that
      microRNAs can promote the evolution of malignant behaviors by regulating multiple
      targets. We performed a microRNA analysis of human melanoma, a highly invasive
      cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic
      potential, shorter time to recurrence, and reduced overall survival. Ectopic
      expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by
      directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis
      of the immunosuppressive cytokine IL-10, and reduced immune cell activation and
      recruitment. These data support a key role of miR-30b/30d and GalNAc transferases
      in metastasis, by simultaneously promoting cellular invasion and
      immunosuppression.

PMID- 21741601
TI  - Targeting androgen receptor in estrogen receptor-negative breast cancer.
AB  - Endocrine therapies for breast cancer that target the estrogen receptor (ER) are
      ineffective in the 25%-30% of cases that are ER negative (ER-). Androgen receptor
      (AR) is expressed in 60%-70% of breast tumors, independent of ER status. How
      androgens and AR regulate breast cancer growth remains largely unknown. We find
      that AR is enriched in ER- breast tumors that overexpress HER2. Through analysis
      of the AR cistrome and androgen-regulated gene expression in ER-/HER2+ breast
      cancers we find that AR mediates ligand-dependent activation of Wnt and HER2
      signaling pathways through direct transcriptional induction of WNT7B and HER3.
      Specific targeting of AR, Wnt or HER2 signaling impairs androgen-stimulated tumor
      cell growth suggesting potential therapeutic approaches for ER-/HER2+ breast
      cancers.

PMID- 21741602
TI  - [Delayed foreign body reaction to steel wire suture resembling basal cell
      carcinoma].

PMID- 21741603
TI  - [Embolia cutis medicamentosa (Nicolau syndrome) after glatiramer acetate
      injection].

PMID- 21741604
TI  - An angiographic and intravascular ultrasound study of the left anterior
      descending coronary artery in takotsubo cardiomyopathy.
AB  - The precise cause of takotsubo cardiomyopathy (TC) remains controversial. Plaque
      rupture with transient thrombotic occlusion of a transapical left anterior
      descending coronary artery (LAD) has been advanced as a potential mechanism. To
      explore this hypothesis, the investigators analyzed data from 11 patients
      prospectively enrolled in the Rhode Island Takotsubo Cardiomyopathy Registry who
      underwent coronary angiography and intravascular ultrasound evaluation of the LAD
      during their initial presentation. Despite the presence of nonobstructive
      coronary artery disease, no culprit lesion was identified in any patient.
      Similarly, the course of the LAD failed to account for the characteristic left
      ventricular apical ballooning seen in TC. In conclusion, an atherosclerotic
      coronary lesion in the LAD causing an aborted myocardial infarction may not be
      the primary underlying cause of TC, and nonobstructive coronary artery disease
      and TC may coexist without a direct causal association.

PMID- 21741605
TI  - Comparison of atherosclerotic plaque by computed tomography angiography in
      patients with and without diabetes mellitus and with known or suspected coronary
      artery disease.
AB  - The aim of this study was to compare coronary artery plaque burden, composition,
      distribution, and the degree of coronary artery stenosis in diabetic and
      nondiabetic patients with known or suspected coronary artery disease (CAD). The
      study group consisted of 594 patients with known or suspected CAD, including 122
      diabetics, who underwent multidetector computed tomographic coronary angiography
      and traditional invasive coronary artery angiography. Coronary artery calcium
      scores were compared in different age subgroups. Noncalcified plaque, calcified
      plaque, and mixed plaque were analyzed by coronary segment on computed
      tomographic coronary angiography, as well as the degree of coronary stenosis on
      coronary artery angiography. Obstructive vessels were compared between the 2
      groups. Total coronary artery calcium score was higher in patients with diabetes
      compared to those without (378.4 +/- 613.0 vs 226.0 +/- 408.4, p = 0.003). The
      percentage of patients with coronary artery calcium scores >400 among diabetics
      (22.1%) was higher than among nondiabetics (14.2%) (p = 0.032). Diabetics had a
      higher percentage of coronary segments with noncalcified plaque, calcified
      plaque, and mixed plaque than nondiabetics (35.3% vs 26.2%, p <0.001; 17.5% vs
      11.6%, p = 0.017; and 9.8% vs 7.9%, p = 0.008). More diabetics had multivessel
      obstructive disease compared to nondiabetics (p <0.05). With longer duration of
      diabetes mellitus, the stenosed segments of coronary arteries increased
      accordingly. In conclusion, diabetics have more atherosclerotic plaque burden and
      more severe coronary atherosclerosis than nondiabetics. Most obstructive lesions
      were caused by mixed plaques in diabetics and nondiabetics.

PMID- 21741606
TI  - Comparison of aerobic versus resistance exercise training effects on metabolic
      syndrome (from the Studies of a Targeted Risk Reduction Intervention Through
      Defined Exercise - STRRIDE-AT/RT).
AB  - Aerobic training (AT) improves the metabolic syndrome (MS) and its component risk
      factors; however, to our knowledge, no randomized clinical studies have addressed
      whether resistance training (RT) improves the MS when performed alone or combined
      with AT. Sedentary, overweight dyslipidemic men and women, aged 18 to 70 years
      completed a 4-month inactive run-in period and were randomized to 1 of 3 eight
      month exercise programs (n = 196). The exercise programs were (1) RT (3
      days/week, 3 sets/day of 8 to 12 repetitions of 8 different exercises targeting
      all major muscle groups); (2) AT (~120 minutes/week at 75% of the maximum oxygen
      uptake), and (3) AT and RT combined (AT/RT) (exact combination of AT and RT). Of
      the 196 randomized patients, 144 completed 1 of the 3 exercise programs. The 86
      participants with complete data for all 5 MS criteria were used in the present
      analysis, and a continuous MS z score was calculated. Eight months of RT did not
      change the MS score. AT improved the MS score (p <0.07) and showed a trend toward
      significance compared to RT (p <0.10). AT/RT significantly decreased the MS score
      and was significantly different from RT alone. In conclusion, RT was not
      effective at improving the MS score; however, AT was effective. Combined AT and
      RT was similarly effective but not different from AT alone. When weighing the
      time commitment versus health benefit, the data suggest that AT alone was the
      most efficient mode of exercise for improving cardiometabolic health.

PMID- 21741607
TI  - Mechanical left ventricular dyssynchrony in heart failure patients with narrow
      QRS duration as assessed by three-dimensional speckle area tracking strain.
AB  - The aim of this study was to assess whether heart failure (HF) patients with
      narrow QRS durations have mechanical left ventricular (LV) dyssynchrony compared
      to those with wide QRS durations and with normal subjects. The strain
      dyssynchrony index with 3-dimensional area tracking (ASDI) was used, which
      represents mechanical LV dyssynchrony and residual endomyocardial function from
      circumferential as well as longitudinal directions. The study included 79
      subjects: 32 HF patients with ejection fractions <= 35% and narrow QRS durations
      (<120 ms) and 22 with ejection fractions <= 35% and wide QRS durations (>= 120
      ms), all candidates for cardiac resynchronization therapy, and 25 normal
      controls. ASDI was calculated as the average difference between peak and end
      systolic area strain of LV endocardium obtained using 3-dimensional speckle
      tracking imaging using 16 LV segments (>= 3.8% predefined as significant). ASDI
      in HF patients with narrow QRS durations was lower than in their counterparts
      with wide QRS durations (2.5 +/- 1.3% vs 4.2 +/- 1.2%, p <0.001) but higher than
      in normal controls (2.5 +/- 1.3% vs 0.73 +/- 0.53%, p <0.001). Furthermore, the
      prevalence of significant ASDI in HF patients with narrow QRS durations was
      significantly higher than in normal controls (22% vs 0%, p = 0.01) but
      significantly lower than in HF patients with wide QRS durations (22% vs 59%, p
      <0.01). In conclusion, HF patients with narrow QRS durations have LV
      dyssynchrony. These observations suggest that the use of 3-dimensional speckle
      area tracking strain might be extended to HF patients with narrow QRS durations
      who are being considered as potential candidates for cardiac resynchronization
      therapy.

PMID- 21741608
TI  - Mechanism and severity of mitral regurgitation by transesophageal
      echocardiography in patients referred for percutaneous valve repair.
AB  - Percutaneous mitral valve repair with the MitraClip has been shown to decrease
      mitral regurgitation (MR) severity, left ventricular volumes, and functional
      class in patients with severe (3+ or 4+) MR. Determination of which patients are
      optimal candidates for MitraClip therapy versus surgery has not been rigorously
      evaluated. Transesophageal echocardiography was prospectively performed in 113
      consecutive patients referred for potential MitraClip therapy under the REALISM
      continued access registry. MR severity was assessed quantitatively in all
      patients. Mitral valve anatomy and feasibility of MitraClip placement were
      assessed by transesophageal echocardiography and clinical parameters. MR was
      degenerative (mitral valve prolapse) in 60 patients (53%), functional
      (anatomically normal) in 44 (39%), and thickened with restricted motion
      (Carpentier IIIB classification) in 9 (8%). MR was mild in 19 patients (17%),
      moderate in 27 (24%), and severe (3 to 4+) in 67 (59%) by Transesophageal
      echocardiography. MitraClip placement was performed in only 17 of 113 patients
      (15%); all were successful. Surgical mitral valve repair was performed in 25
      patients (22%), mitral valve replacement in 12 (11%). Most patients (59 of 113,
      52%) were treated medically, usually because MR was not severe enough to warrant
      intervention. In conclusion, most patients referred for MitraClip therapy do not
      have severe enough MR to warrant intervention. Of those with clinical need for
      intervention, surgery is more often recommended for anatomic or clinical reasons.
      Three-dimensional transesophageal echocardiography with quantitative assessment
      of MR severity is helpful in evaluating these patients.

PMID- 21741609
TI  - Effect of smoking relapse on outcome after acute coronary syndromes.
AB  - The aim of the present study was to evaluate the smoking relapse rate among
      smokers who had become abstinent during admission for acute coronary syndromes.
      The association between smoking relapse and mortality was also analyzed. A cohort
      of 1,294 consecutive active smokers who had interrupted smoking after admission
      for acute coronary syndromes (1,018 men and 276 women, mean age 59.7 +/- 12.3
      years) was followed up for 12 months after the index admission. All patients
      received a brief in-hospital smoking cessation intervention consisting of
      repeated counseling sessions. During follow-up, 813 patients (62.8%) resumed
      regular smoking (median interval to relapse 19 days, interquartile range 9 to
      76). Increasing age (hazard ratio [HR] 1.034 per year, 95% confidence interval
      [CI] 1.028 to 1.039, p = 0.001) and female gender (HR 1.23, 95% CI 1.09 to 1.42,
      p = 0.03) were independent predictors of smoking relapse. Patients enrolled in a
      cardiac rehabilitation program (HR 0.74, 95% CI 0.51 to 0.91, p = 0.02) and those
      with diabetes (HR 0.79, 95% CI 0.68 to 0.94, p = 0.03) were more likely to remain
      abstinent. During follow-up, 97 patients died (1-year probability of death 0.075,
      95% CI 0.061 to 0.090). Multivariate analysis with the Cox proportional hazard
      regression method, including smoking relapse as a time-dependent covariate,
      demonstrated that, after adjustment for patient demographics, the clinical
      history features and variables related to the index event, the resumption of
      smoking was an independent predictor of total mortality (HR 3.1, 95% CI 1.3 to
      5.7, p = 0.004). In conclusion, smoking relapse after acute coronary syndromes is
      associated with increased mortality, and counseling interventions should be
      integrated into the postdischarge support to reduce the negative effects of
      smoking resumption.

PMID- 21741610
TI  - Predictors of low clopidogrel adherence following percutaneous coronary
      intervention.
AB  - Few data are available on factors associated with low adherence or early
      clopidogrel discontinuation after percutaneous coronary intervention (PCI).
      Patients (n = 284) were evaluated before hospital discharge after PCI to identify
      factors associated with low adherence to clopidogrel 30 days later. Adherence to
      daily medications before PCI was assessed using the 8-item Morisky Medication
      Adherence Scale (MMAS-8) and categorized as low (score <6), medium (score 6 to
      <8), or high (score 8). Low adherence to clopidogrel was defined as MMAS-8 score
      <6 (n = 21) or having discontinued clopidogrel (n = 11), which was ascertained
      during a 30-day interview after PCI. At 30 days after PCI, 11% of patients had
      low adherence to clopidogrel. Odds ratios (95% confidence intervals [CIs]) for
      low adherence to clopidogrel were 3.78 (1.09 to 13.1), 3.06 (1.36 to 6.87), 2.46
      (0.97 to 6.27), and 3.36 (0.99 to 11.4) for patients who before PCI reported
      taking smaller doses of medication because of cost, had difficulty filling
      prescriptions, had difficulty reaching their primary physician, and were not
      comfortable asking their doctor for instructions, respectively. Odds ratios (95%
      CIs) for low clopidogrel adherence after PCI in patients with medium and low
      versus high adherence to daily medications before PCI were 6.13 (1.34 to 28.2)
      and 10.9 (2.46 to 48.7), respectively. The c-statistic associated with MMAS-8
      scores before PCI for discriminating low clopidogrel adherence at 30 days after
      PCI was 0.733 (95% CI 0.650 to 0.852). In conclusion, adherence to daily
      medications before PCI may be a useful indicator for identifying patients who
      will have low clopidogrel adherence after PCI.

PMID- 21741611
TI  - Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption,
      and supernumerary teeth.
AB  - Craniosynostosis and supernumerary teeth most often occur as isolated
      developmental anomalies, but they are also separately manifested in several
      malformation syndromes. Here, we describe a human syndrome featuring
      craniosynostosis, maxillary hypoplasia, delayed tooth eruption, and supernumerary
      teeth. We performed homozygosity mapping in three unrelated consanguineous
      Pakistani families and localized the syndrome to a region in chromosome 9.
      Mutational analysis of candidate genes in the region revealed that all affected
      children harbored homozygous missense mutations (c.662C>G [p.Pro221Arg], c.734C>G
      [p.Ser245Cys], or c.886C>T [p.Arg296Trp]) in IL11RA (encoding interleukin 11
      receptor, alpha) on chromosome 9p13.3. In addition, a homozygous nonsense
      mutation, c.475C>T (p.Gln159X), and a homozygous duplication, c.916_924dup
      (p.Thr306_Ser308dup), were observed in two north European families. In cell
      transfection experiments, the p.Arg296Trp mutation rendered the receptor unable
      to mediate the IL11 signal, indicating that the mutation causes loss of IL11RA
      function. We also observed disturbed cranial growth and suture activity in the
      Il11ra null mutant mice, in which reduced size and remodeling of limb bones has
      been previously described. We conclude that IL11 signaling is essential for the
      normal development of craniofacial bones and teeth and that its function is to
      restrict suture fusion and tooth number. The results open up the possibility of
      modulation of IL11 signaling for the treatment of craniosynostosis.

PMID- 21741613
TI  - Survival rates in extremely low birthweight infants depend on the denominator:
      avoiding potential for bias by specifying denominators.
AB  - OBJECTIVE: The objective of the study was to assess whether recent data reporting
      survival of preterm infants introduce a bias from the use of varying
      denominators. STUDY DESIGN: We performed a systematic review of hospital survival
      of infants less than 1000 g or less than 28 weeks. Included publications
      specified the denominator used to calculate survival rates. RESULTS: Of 111
      eligible publications only 51 (46%) specified the denominators used to calculate
      survival rates: 6 used all births, 25 used live births, and 20 used neonatal
      intensive care unit admissions. Overall rates of survival to hospital discharge
      ranged widely: from 26.5% to 87.8%. Mean survival varied significantly by
      denominator: 45.0% (+/-11.6) using a denominator of all births, 60.7% (+/-13.2)
      using live births, or 71.6% (+/-12.1) using used neonatal intensive care unit
      admissions (P <= .009 or less for each of 3 comparisons). CONCLUSION: Variations
      in reported rates of survival to discharge for extremely low-birthweight (<1000
      g) and extremely low-gestational-age (<28 weeks) infants reflect in part a
      denominator bias that dramatically affects reported data.

PMID- 21741614
TI  - Pregestational, periconceptional, and gestational primary maternal
      cytomegalovirus infection: prenatal diagnosis in 508 pregnancies.
AB  - OBJECTIVE: The objective of the study was to evaluate the vertical transmission
      rate and fetal risk following primary maternal cytomegalovirus infection before
      and around conception. STUDY DESIGN: Data of patients referred to fetal medicine
      clinic in 1 tertiary center in Israel were evaluated. Each included subject had
      primary maternal cytomegalovirus infection determined by serology, precise
      gestational dating, and testing of fetal infection. Subjects were assigned to
      five subgroups: pregestational, periconception, and first, second, or third
      trimester of pregnancy. RESULTS: Five hundred eight pregnancies were included.
      None of the 97 pregnancies in the preconception group and 6 of the 130
      periconception subjects (4.6%) were congenitally infected. Transmission rates
      were 34.8%, 42.0%, and 58.6% for the first, second, and third trimesters,
      respectively (P = .049). Prenatal and postnatal follow-up indicated that third
      trimester infection has no clinical effect on the fetus. CONCLUSION: Pre- and
      periconception maternal infection carries small risk for fetal infection, whereas
      it is positively correlated to time of maternal infection during pregnancy.

PMID- 21741615
TI  - Cumulative radiation dose from medical imaging procedures in patients undergoing
      resection for lung cancer.
AB  - BACKGROUND: Radiation dose from diagnostic imaging procedures is not monitored in
      patients undergoing surgery for lung cancer. Evidence suggests an increased
      lifetime risk of malignancy of 1.0% per 100 millisieverts (mSv). As such,
      recommendations are to restrict healthcare and radiation workers to a maximum
      dose of 50 mSv per year or to 100 mSv over a three-year period. The purpose of
      this study was to estimate cumulative effective doses of radiation in patients
      undergoing lung cancer resection and to determine predictors of increased
      exposure. METHODS: We identified 94 consecutive patients undergoing resection for
      non-small cell lung cancer. Radiologic procedures performed from one year prior
      to resection until two years postresection were recorded. Estimates of effective
      doses (mSv) were obtained from published literature and institutional records.
      Predictors of dose greater than 50 mSv per year and greater than 100 mSv per
      three years were examined statistically. RESULTS: The majority of patients
      (median age = 67 years) had stage IA cancer (52%). In the three-year period,
      patients had 1,958 radiologic studies (20.8/patient) including 398 computed
      tomographic (CT) scans (4.23/patient) and 211 positron emission tomography (PET)
      scans (2.24 per patient). The three-year median estimated radiation dose was 84.0
      mSv (interquartile range, 44.1 to 123.2 mSv). The highest dose was in the
      preoperative year. In any one year, 66% of patients received more than 50 mSv,
      while 19% received over 100 mSv. Over the three-year period, 43.6% of patients
      exceeded 100 mSv. The majority of the radiation (89.8%) was from CT or PET scans.
      On multivariate analysis, a history of previous malignancy (odds ratio [OR] 3.8;
      confidence interval [CI] 1.14 to 12.7), postoperative complications (OR 6.16; CI
      1.42 to 26.6), and postoperative surveillance with PET-CT (OR 13.2; CI 4.34 to
      40.3) predicted exposure greater than 100 mSv over the three-year period.
      CONCLUSIONS: This study demonstrates that lung cancer patients often receive a
      higher dose of radiation than that considered safe for healthcare and radiation
      workers. The median cumulative dose reported in this study could potentially
      increase the individual estimated lifetime cancer risk by as much as 0.8%.
      Although risk-benefit considerations are clearly different between these groups,
      strategies should be in place to decrease radiation doses during the preoperative
      workup and postoperative period.

PMID- 21741616
TI  - Comparative analysis of tumour angiogenesis in solid multicystic and unicystic
      ameloblastoma by using CD 105 (endoglin).
AB  - OBJECTIVE: The aim of the present study was to evaluate and compare the
      expression of CD105 (endoglin) in solid multicystic ameloblastoma (SMA) and
      unicystic ameloblastoma (UA). MATERIALS AND METHODS: Angiogenesis was assessed in
      20 SMA, 15 UA and 10 normal oral mucosa samples by measuring the mean vascular
      density (MVD), total vascular area (TVA) and mean vascular area (MVA). The
      immunohistochemistry was carried out by using monoclonal mouse anti-human
      antibody against CD105. RESULTS: The Kruskal-Wallis test showed significant
      difference in mean MVD, TVA, and MVA between SMA, UA, and control group
      (p<0.001). Using the Mann-Whitney test, the mean MVD, TVA and MVA, was
      statistically significant between SMA and control group (p<0.001) as well as
      between UA and control group (p<0.001). No significant difference of mean MVD,
      TVA, and MVA, was observed between SMA and UA (p>0.05). CONCLUSION: Our study
      results show no significant difference in MVD, TVA and MVA between SMA and UA.
      This may reflect the fact that though clinical behaviour, histopathological
      presentation and prognosis of SMA and UA differ, the process of angiogenesis is
      not different. This suggests that the angiogenesis has an important role in
      tumour progression and invasiveness of ameloblastoma. Measurement and assessment
      of tumour angiogenesis may prove very valuable in predicting response to
      antiangiogenic therapeutic strategies and also provide objective assessment of
      post therapeutic response particularly in recurrent cases of SMA and UA.

PMID- 21741617
TI  - Fatty-acid profiles and expression of the fabM gene in a fluoride-resistant
      strain of Streptococcus mutans.
AB  - OBJECTIVE: The aim of this study was to compare the membrane fatty acid profile
      and expression of the fabM gene in a fluoride-resistant Streptococcus mutans
      strain with those of its wild-type counterpart. Additionally, we aimed to
      investigate whether mutations were present in the fabM gene of the fluoride
      resistant strain. DESIGN: A fluoride-resistant strain of S. mutans was obtained
      by step-by-step induction in vitro. The fluoride-resistant strain and its wild
      type counterpart were grown anaerobically in a brain heart infusion broth,
      harvested and resuspended in a salt solution for an acid survival assay and a pH
      drop experiment. The membrane fatty acid profile was determined by gas
      chromatography-mass spectrometry. Expression of the fabM gene was quantified by
      real-time PCR. The fabM gene was also sequenced. RESULTS: The ability of the
      fluoride-resistant strain to resist acid stress was greater than that of the wild
      type strain. A significant difference in the amount of long-chain monounsaturated
      fatty acids between the fluoride-resistant strain and the wild-type strain was
      detected in acidic condition (P<0.01). In addition, the level of fabM mRNA in the
      fluoride-resistant strain was significantly higher than that of the wild-type
      strain in the acidic condition as well (P<0.01). However, the sequence of the
      fabM gene from the fluoride-resistant strain was 100% homologous with that from
      the wild-type strain. CONCLUSIONS: The membrane fatty acid profile and expression
      of the fabM gene in the fluoride-resistant strain were altered compared to the
      wild-type strain in acidic conditions, but no differences were found in the
      sequence of the fabM gene.

PMID- 21741618
TI  - Effects of short term forced oral breathing: physiological changes and structural
      adaptation of diaphragm and orofacial muscles in rats.
AB  - OBJECTIVE: We studied adaptation of diaphragm and orofacial muscles as well as
      hormonal responses to forced oral breathing (lasting for only 4 days) following
      reversible bilateral nasal obstruction performed on day 8 post-natal male rats.
      DESIGN: Muscle myosin heavy chain (MHC) composition and hormone levels were
      analysed during two periods: 1 and 3 days after obstruction (days 9 and 11 post
      natal), and following 3 months recovery with nasal breathing (90 days, adult).
      RESULTS: Diaphragm muscle showed significant increases in adult isoforms (MHC 1,
      2a) in oral breathing group versus control. We observed increases in MHC neonatal
      and adult type 1 isoforms in muscles involved with oral breathing, masseter
      superficialis and anterior digastric. No changes were observed in the levator
      nasolabialis muscle involved with nasal breathing. Reversible nasal obstruction
      was associated with reduced growth of the olfactory bulbs lasting into adulthood,
      and an initial decrease in lung growth followed by recovery at 90 days. Adrenal
      hypertrophy was observed after 1 day of nasal obstruction and lasted into
      adulthood. The "stress" hormone response was variable, increased (over 1000%)
      during the obstruction but normal by adulthood. An increase in plasma
      testosterone was observed during the obstruction, and a decrease in thyroid
      hormone levels throughout. CONCLUSIONS: Very short term nasal obstruction, i.e.
      forced oral breathing, leads to long term hormonal changes and respiratory muscle
      fibre adaptation.

PMID- 21741619
TI  - Enhancement of carbachol-induced amylase secretion in parotid glands from rats
      with experimental periodontitis.
AB  - OBJECTIVE: In a previous study we observed that parotid glands from rats with
      experimental periodontitis showed an increase in basal amylase release as a
      result of an increase in cAMP accumulation induced by PGE(2) production. The aim
      of this work was to study whether this change in amylase release influences the
      secretory effect of carbachol. DESIGN: Experimental periodontitis was induced
      through placing a black thread around the cervix of the two lower first molars.
      Experiments were done 22 days after ligature induced periodontitis. Amylase
      release was evaluated in vitro and determined using a colorimetric method which
      uses starch as substrate. RESULTS: The effect of carbachol was increased in
      parotid glands from periodontitis rats. The effect of 10(-6)M carbachol was
      inhibited by 4-DAMP (10(-6)M), U-73122 (5 * 10(-6)M) and trifluoperazine (5 * 10(
      6)M) in both groups. No changes were observed in the binding sites and affinity
      in parotid membranes from rats with experimental periodontitis. The inhibition of
      the adenylyl cyclase and the cyclooxygenase induced a right shift of the
      carbachol concentration-response curve in periodontitis group whilst the opposite
      effect was observed in control group in the presence of db-cAMP and PGE(2).
      CONCLUSIONS: Parotid glands from rats with experimental periodontitis release
      more amylase in response to carbachol suggesting an interaction between Ca(2+)
      and cAMP in the fusion/exocytosis step of secretory vesicles.

PMID- 21741620
TI  - MP-124, a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor, ameliorates
      ischemic brain damage in a non-human primate model.
AB  - Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) in response to DNA
      damage is considered to play a crucial role in the development of post-ischemic
      neuronal injury, such as ischemic stroke. The present study was undertaken to
      clarify the beneficial effects of MP-124, a novel PARP-1 inhibitor, on
      neurological deficits and cerebral infarcts following middle cerebral artery
      occlusion (MCAO) in the monkey. The effects of MP-124 on cerebral infarcts and
      neurological deficits in monkeys were investigated in permanent MCAO (pMCAO) and
      transient MCAO (tMCAO) models. In a dose-dependency study, the neurological
      deficits and cerebral infarct volume were assessed at 28h after pMCAO. MP-124
      significantly reduced the total infarct volume, including that in the
      cortex/white matter and striatum, at doses of 0.3, 1 and 3mg/kg/h by 22, 54 and
      64%, respectively. In addition, MP-124 at all doses significantly reduced the
      overall neurological deficits. Such ameliorative effects of MP-124 were observed
      in female as well as male monkeys. In the therapeutic time window (TTW) study,
      the neurological deficits and cerebral infarct volume were assessed at several
      time points after pMCAO or tMCAO. Treatment with MP-124 at 3 and 6h after MCAO
      significantly ameliorated not only the neurological deficits but also the infarct
      volume. MP-124 is thought to exhibit neuroprotective effects with a broad TTW
      regardless of sex in MCAO models. Such findings suggest that MP-124 may be
      beneficial for the treatment of acute ischemic stroke.

PMID- 21741621
TI  - Detailed characterization of neuro-immune responses following neuropathic injury
      in mice.
AB  - Partial sciatic nerve injury is a common model of neuropathic pain in rodents,
      and produces both mechanical and thermal pain hypersensitivity. Several types of
      immune cells have been implicated in the pathogenesis of neuropathic pain due to
      nerve injury; however, the timing of their appearance has not been fully
      elucidated. Here, using immunohistochemistry, we characterized the time course
      and magnitude of inflammatory cell infiltration and resident immune cell
      activation in the sciatic nerves, L3-5 dorsal root ganglia (DRGs) and spinal
      segments following partial ligation of the sciatic nerve (PSNL) in C57BL/6J mice.
      PSNL markedly decreased paw withdrawal threshold to mechanical stimuli and paw
      withdrawal latency to thermal stimuli in the injured side. No changes were
      observed in the uninjured contralateral side. Mechanical allodynia persisted, and
      thermal hyperalgesia resolved by 2weeks after injury. We found a significant
      increase in the numbers of infiltrating neutrophils, macrophages, dendritic cells
      and lymphocytes in the injured sciatic nerve and ipsilateral DRGs in comparison
      to sham-operated controls, with different timelines of recruitment for each cell
      type. Expression of ATF3 in the cell bodies of DRG neurons indicated about 30-40%
      neuronal damage. No neutrophils, dendritic cells, or lymphocytes were found in
      the spinal cord. However, a significant increase in the level of microglial and
      astrocytic activation was observed in the spinal dorsal horn and to a lesser
      extent in the ventral horn, peaking on days 7 and 14 after nerve injury. These
      changes corresponded with a significant increase in immunoreactivity for
      phosphorylated NR1 subunit of the NMDA receptor, and a significant decrease in
      IB4-labeled non-peptidergic nociceptive terminals in the ipsilateral dorsal horn.
      Our findings suggest differential roles for peripheral and central neuroimmune
      interactions in the production of neuropathic pain.

PMID- 21741622
TI  - Effect of tooth pulp and periaqueductal central gray electrical stimulation on
      beta-endorphin release into the fluid perfusing the cerebral ventricles in rats.
AB  - Our previous studies demonstrated that tooth pulp stimulation increases the pain
      threshold, whereas stimulation of the periaqueductal central gray (PAG) has the
      opposite effect. The aim of this study was to investigate the effect exerted by
      electrical stimulation of the nociceptive afferent terminals in the tooth pulp
      and analgesic electrical stimulation of the PAG on the release of immunoreactive
      beta-endorphin (beta-EP-IR) into the cerebrospinal fluid (CSF) and artificial
      cerebrospinal fluid (aCSF) perfusing the cerebral ventricles in rat, and to
      establish whether during such stimulation the MU-opioid receptor (MOR) was
      activated. The tongue jerk reflex was induced by dental pulp stimulation in rats
      under chloralose anesthesia. CSF was collected from the cerebello-medullary
      cistern, and then 30-minute perfusions of the lateral ventricles with aCSF were
      conducted with collection of perfusate portions from the cerebello-medullary
      cistern at rest (control), during electrical tooth pulp stimulation evoking the
      nociceptive tongue jerk reflex and during inhibition of that reflex with
      simultaneous stimulation of tooth pulp and the PAG. In the second series of
      experiments, a MOR-selective antagonist, beta-funaltrexamine (beta-FNA) was
      perfused through the cerebral ventricles 10min before tooth pulp stimulation.
      beta-EP-IR was determined in the collected CSF and aCSF perfusates by
      radioimmunoassay (RIA). Stimulation of tooth pulp with electrical impulses
      resulted in a significant increase of beta-EP-IR. On the other hand, simultaneous
      tooth pulp and PAG stimulation inhibited beta-EP-IR release into the fluid
      perfusing the cerebral ventricles. beta-FNA blocked evoked tongue jerks (ETJ)
      induced by PAG stimulation, but no enhancing effect of beta-FNA on beta-EP-IR
      release into the perfusate was observed. The obtained results indicate that
      stimulation of the tooth pulp increases beta-EP release significantly, whereas
      PAG stimulation significantly inhibits beta-EP-IR release into the CSF, and that
      these effects are mediated by MOR. The results of the experiments allow to
      conclude that endogenous beta-EP, released as a result of electrical tooth pulp
      stimulation in orofacial pain, diffuses through the cerebroventricular ependyma
      into the CSF and exerts a modulatory effect, mediated by MOR, alterating the
      properties of neurons in the trigeminal sensory nuclei, interneurons, and
      motoneurons of the hypoglossal nerve.

PMID- 21741623
TI  - Developmental expression of muscarinic receptors in the eyes of zebrafish.
AB  - In previous work, we have shown that light-adaptive pigment granule dispersion
      can be induced in vitro by treating retinal pigment epithelium (RPE) isolated
      from bluegill retina with acetylcholine or its analog carbachol and that these
      agents act through muscarinic receptors to induce pigment granule dispersion. RPE
      is a monolayer of tissue found between the neural retina and the choroid. In
      fish, RPE has long apical projections enmeshed with the distal part of
      photoreceptors, reaching down to the level of their nuclei. The RPE disperses
      melanin pigment granules into the apical projections to shield light-sensitive
      photoreceptor outer segments from photobleaching when fish are under bright-light
      conditions. During development, RPE begin to respond to light at 5days post
      fertilization, raising the question of whether responsiveness is correlated to
      receptor expression. Here, we isolate, clone and sequence chrm-odd receptor genes
      in zebrafish, characterize them phylogenetically and observe their expression in
      the eyes of the zebrafish at different developmental stages using RT-PCR and
      immunofluorescence microscopy. We find that zebrafish express six unique chrm-odd
      receptor subtypes: chrm1a, chrm1b, chrm3a, chrm3b, chrm5a and chrm5b - and these
      receptors are differentially expressed during development. Our phylogenetic
      analysis confirms the assignments of chrm1b and chrm5b, isolated here, as well as
      other muscarinic receptor genes and their duplicates and suggests previously
      described muscarinic receptors may need to be reclassified. Differences between
      the expression patterns of ostensibly duplicated genes raise the possibility that
      subtle differences between the duplicates may enable refined regulation of
      specific developmental events.

PMID- 21741624
TI  - Quantitative prediction of acute ischemic tissue fate using support vector
      machine.
AB  - Accurate and quantitative prediction of ischemic tissue fate could improve
      decision-making in the clinical treatment of acute stroke. The goal of the
      present study is to explore the novel use of support vector machine (SVM) to
      predict infarct on a pixel-by-pixel basis using only acute cerebral blood flow
      (CBF), apparent diffusion coefficient (ADC) MRI data. The efficacy of SVM
      prediction model was tested on three stroke groups: 30-min, 60-min, and permanent
      middle cerebral-artery occlusion (n=12 rats for each group). CBF, ADC and
      relaxation time constant (T2) were acquired during the acute phase up to 3h and
      again at 24h. Infarct was predicted using only acute (30-min) stroke data.
      Receiver-operating characteristic (ROC) analysis was used to quantify prediction
      accuracy. The areas under the receiver-operating curves were 86+/-2.7%, 89+/
      1.4%, and 93+/-0.8% using ADC+CBF data for the 30-min, 60-min and permanent
      middle cerebral artery occlusion (MCAO) group, respectively. Adding neighboring
      pixel information and spatial infarction incidence improved performance to 88+/
      2.8%, 94+/-0.8%, and 97+/-0.9%, respectively. SVM prediction compares favorably
      to a previously published artificial neural network (ANN) prediction algorithm
      operated on the same data sets. SVM prediction model has the potential to provide
      quantitative frameworks to aid clinical decision-making in the treatment of acute
      stroke.

PMID- 21741625
TI  - Ethanol-induced effects on the dopamine and serotonin systems in adult Wistar
      rats are dependent on early-life experiences.
AB  - Some individuals control their ethanol consumption throughout life, but others
      escalate their intake to levels that increase the risk for addiction. The early
      environment influences the individual response to ethanol and affects the
      underlying physiological processes that lead to a transition from a voluntary to
      a compulsive use of ethanol. However, the neurobiological substrates for these
      processes are not understood. The present study aimed to test the hypothesis that
      early environmental experiences affect the neurobiological effects that are
      induced by voluntary ethanol consumption. Rat pups were subjected to three
      different rearing environments: conventional animal facility rearing or
      separation from dam and littermates for either 15 or 360min. In adulthood, the
      rats were exposed to a two-bottle free choice between ethanol and water for seven
      weeks. Tissue levels of dopamine, 5-hydroxytryptamine (5-HT) and their
      metabolites were measured in brain areas that have been implicated in reward and
      addiction processes. Differences in ethanol-induced effects were noted in 5-HT
      related measurements in the nucleus accumbens and ventral tegmental area and in
      dopamine-related measurements in the dorsal raphe nucleus (DRN). These results
      provided evidence of an early environmental impact on interactive neuronal
      circuits between the DRN and reward pathways. The amygdala, a key area in
      addiction processes, was particularly sensitive to early-life conditions. The
      animals that experienced the longest separation differed from the others; they
      had low basal 5-HT levels and responded with an increase in 5-HT after ethanol.
      These altered responses to initial ethanol consumption as a result of early
      environmental factors may affect the transition from habitual to compulsive
      drinking and contribute to individual vulnerability or resilience to addiction.

PMID- 21741626
TI  - Acidic resin-catalysed conversion of fructose into furan derivatives in low
      boiling point solvents.
AB  - Conversion of fructose into furan derivatives 5-hydroxymethylfurfural (HMF) and 5
      methoxymethylfurfural (MMF) is performed in tetrahydrofuran (THF) and methanol
      organic solvent systems, catalysed by an acidic resin Amberlyst-15. The melted
      fructose can be converted into HMF on the surface of the solid resin catalyst in
      the presence of THF as an extracting phase, which is a good solvent for HMF and
      other by-products. The solid resin catalyst can be reused eleven times without
      losing its catalytic ability, with an average HMF yield of approximately 50%.
      Upon the addition of methanol, the generated HMF can further react with methanol
      to form MMF, and the total yield of HMF and MMF could be promoted to 65%. GC-MS
      analysis confirms the formation of a small amount of methyl levulinate in
      methanolorganic solvent system.

PMID- 21741627
TI  - Crystal and molecular structure of methyl L-glycero-alpha-D-manno
      heptopyranoside, and synthesis of 1->7 linked L-glycero-D-manno-heptobiose and
      its methyl alpha-glycoside.
AB  - Methyl l-glycero-alpha-d-manno-heptopyranoside was synthesized in good yield by a
      Fischer-type glycosylation of the heptopyranose with methanol in the presence of
      cation-exchange resin under reflux and microwave conditions, respectively. The
      compound crystallized from 2-propanol in an orthorhombic lattice of space group
      P2(1)2(1)2 showing a comparatively porous structure with a 2-dimensional O-H?O
      hydrogen bond network. As model compounds for the side chain domains of the inner
      core structure of bacterial lipopolysaccharide, l-glycero-alpha-d-manno
      heptopyranosyl-(1->7)-l-glycero-d-manno-heptopyranose and the corresponding
      disaccharide methyl alpha-glycoside were prepared. The former compound was
      generated via glycosylation of a benzyl 5,6-dideoxy-hept-5-enofuranoside
      intermediate followed by catalytic osmylation and deprotection. The latter
      disaccharide was efficiently synthesized in good yield by a straightforward
      coupling of an acetylated N-phenyltrifluoroacetimidate heptopyranosyl donor to a
      methyl 2,3,4,6-tetra-O-acetyl heptopyranoside acceptor derivative followed by
      Zemplen deacetylation.

PMID- 21741628
TI  - High molecular weight isoforms of growth hormone in cells of the immune system.
AB  - A substantial body of research exists to support the idea that cells of the
      immune system produce growth hormone (GH). However, the structure and mechanism
      of action of lymphocyte-derived GH continues to remain largely unknown. Here we
      present the results of Western analysis of whole cell extracts showing that
      different molecular weight isoforms of GH of approximately 100, 65, and 48 kDa
      can be detected in primary mouse cells of the immune system and in the mouse EL4
      cell line. The identity of the 65 and 48 kDa isoforms of GH were confirmed by
      mass spectrometry. The various isoforms were detected in both enriched T and B
      spleen cell populations. The large molecular weight isoform appears to reside
      primarily in the cytoplasm, whereas the lower molecular weight 65 and 48 kDa
      isoforms were detected primarily in the nucleus. These results also suggest that
      GH isoforms are induced by oxidative stress. In EL4 cells overexpressing GH, the
      expression of luciferase controlled by a promoter containing the antioxidant
      response element is increased almost threefold above control. The data suggest
      that the induction of isoforms of the GH molecule in cells of the immune system
      may be an important mechanism of adaptation and/or protection of lymphoid cells
      under conditions of oxidative stress.

PMID- 21741629
TI  - Melanoma-induced suppression of tumor antigen-specific T cell expansion is
      comparable to suppression of global T cell expansion.
AB  - We have observed that in vivo interaction between melanoma and resting T cells
      promotes suppression of antigen-driven proliferative T cell expansion. We
      hypothesized that this suppression would affect tumor antigen-specific T cell
      populations more potently than tumor-unrelated T cell populations. A B16F10 cell
      line was stably transfected to express low levels of the lymphocytic
      choriomeningitis virus (LCMV) glycoprotein GP33 (B16GP33). Mice bearing B16F10 or
      B16GP33 tumors were infected with LCMV, and proliferative expansion of LCMV
      epitope-specific T cell populations was quantified. In vitro and in vivo assays
      confirmed low levels of antigenic GP33 expression by B16GP33 tumors. Suppressed
      expansion of GP33-specific T cells was equivalent between mice bearing B16F10 and
      B16GP33 tumors. These observations suggest that the ability of growing melanoma
      tumors to impair antigen-driven proliferative expansion of activated T cells is
      global and not antigen-specific, and provide further insight into the influence
      of cancer on activated T cell homeostasis.

PMID- 21741630
TI  - Effect of orexin-A on phagocytic activity of peritoneal macrophage in starved
      rats.
AB  - The aim of this study was to investigate the effect of fasting-induced orexin-A
      (OXA) on inflammation and macrophage phagocytic activity. Fifty six male wistar
      rats were fasted for 36 h to stimulate OXA synthesis. In 24 rats, air pouches
      were induced subcutaneously in the intrascapular area. After (6 h) carrageenan
      injection into the pouches, the contents of the air pouches were removed. The
      exudate volume, protein content and cell count were measured. After the
      determination of fasting on inflammation, the peritoneal macrophages were
      collected from 32 rats to investigate the effect of fasting-induced OXA on
      macrophage phagocytic activity. Plasma OXA levels were markedly higher in fasted
      rats compared with control rats. The phagocytic capability of peritoneal
      macrophages was obtained as a percentage of phagocytosing macrophages and number
      of phagocytosed particles per cell. In spite of increased blood OXA level SB
      334867, selective orexin type 1 receptor antagonist (10 mg/kg) did not change
      phagocytic activity of peritoneal macrophages. These findings indicate that 36 h
      fasting-induced OXA has no significant effect to phagocytosis of peritoneal
      macrophages.

PMID- 21741631
TI  - Breast screening policy: are we heading in the right direction?
AB  - There is a large body of evidence supporting 2-yearly screening of women aged 50
      69 years. There is good evidence for a mortality reduction from mammographic
      screening in women aged 40 to 49 years but a 1-year interval is required. The
      lack of specificity of screening in young women does remain a problem. There is
      no evidence to suggest that a single screen between the ages of 47 and 50 years
      within a programme screening at 3-year intervals will reduce mortality; the
      trials showing a mortality benefit in women in their 40s included multiple
      screening episodes and shorter screening intervals. There is no randomized,
      controlled trial evidence to support screening in women aged above 70 years and
      screening this age group will cause greater harm than in younger women through
      higher rates of over-diagnosis and consequent over-treatment. The randomized
      phase of the screening age extension, which at the moment is planned to last only
      6 years, should not be immediately followed by general implementation of the
      policy. Only if and when additional mortality reductions and an acceptable
      balance between benefit and harms are shown to be achieved by the extra screens
      should the 2007 Cancer Reform Strategy policy on age extension be implemented.
      Resources saved by delaying or abandoning the roll-out of the age extension could
      potentially be redirected towards reducing the current 3 year screening interval
      to 2 years in women aged 50-69 years. However, reducing the screening interval to
      2 years for women aged 50-69 years would require significantly more screening
      invitations and resources than the proposed age extension.

PMID- 21741632
TI  - Commentary on: breast screening policy: are we heading in the right direction?

PMID- 21741633
TI  - Changes in auditory frequency guide visual-spatial attention.
AB  - How do the characteristics of sounds influence the allocation of visual-spatial
      attention? Natural sounds typically change in frequency. Here we demonstrate that
      the direction of frequency change guides visual-spatial attention more strongly
      than the average or ending frequency, and provide evidence suggesting that this
      cross-modal effect may be mediated by perceptual experience. We used a Go/No-Go
      color-matching task to avoid response compatibility confounds. Participants
      performed the task either with their heads upright or tilted by 90 degrees ,
      misaligning the head-centered and environmental axes. The first of two colored
      circles was presented at fixation and the second was presented in one of four
      surrounding positions in a cardinal or diagonal direction. Either an ascending or
      descending auditory-frequency sweep was presented coincident with the first
      circle. Participants were instructed to respond to the color match between the
      two circles and to ignore the uninformative sounds. Ascending frequency sweeps
      facilitated performance (response time and/or sensitivity) when the second circle
      was presented at the cardinal top position and descending sweeps facilitated
      performance when the second circle was presented at the cardinal bottom position;
      there were no effects of the average or ending frequency. The sweeps had no
      effects when circles were presented at diagonal locations, and head tilt entirely
      eliminated the effect. Thus, visual-spatial cueing by pitch change is narrowly
      tuned to vertical directions and dominates any effect of average or ending
      frequency. Because this cross-modal cueing is dependent on the alignment of head
      centered and environmental axes, it may develop through associative learning
      during waking upright experience.

PMID- 21741634
TI  - Some suggestions for the DSM-5 schizotypal personality disorder construct.
AB  - This study relates to the schizotypal personality disorder (SPD) proposal of the
      upcoming fifth edition of the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-5) by investigating the construct validity of SPD as defined by
      DSM-IV in a large sample of patients from the Norwegian Network of Personality
      Focused Treatment Programs (N = 2619), assessed by structured diagnostic
      interviews and the Longitudinal, Expert All Data standard. We investigated factor
      structure and psychometric properties of the SPD criteria, as well as co
      occurrence patterns between SPD and other PDs. Thirty-six patients were diagnosed
      with SPD and 513 patients (21%) endorsed at least 2 schizotypal criteria. We
      found that 2 factors were specific for SPD, a cognitive-perceptual factor (ideas
      of reference, magical thinking, and unusual perceptual experiences) and an
      oddness factor (odd thinking and speech, constricted affect, and odd appearance
      or behavior). The criteria belonging to these factors had appropriate
      psychometric properties. The criteria of the cognitive-perceptual factor were
      more strongly associated with borderline personality disorder (PD) than with the
      other PDs. We did not find support for a consistent factor that reflected
      interpersonal problems. The criteria that used to be part of this factor
      (suspiciousness, lack of friends or confidants, and excessive social anxiety)
      performed poorly as specific SPD criteria. SPD was more strongly associated with
      antisocial PD and paranoid PD than with the other PDs. We suggest that ideas of
      reference should be included explicitly under the schizotypal facet of cognitive
      dysregulation in DSM-5, with less emphasis on the social phobic aspects of this
      feature. Furthermore, there should be more emphasis on the cognitive aspects of
      suspiciousness in SPD, and it should be considered to split up the affectivity
      criterion into constricted affect and inappropriate affect, with the latter type
      of affect being the expression of problems with intersubjective regulation.
      Finally, it is suggested that interpersonal dysfunction is secondary to the 2
      primary SPD factors. Therefore, the SPD narrative should start by describing
      eccentricity and cognitive-perceptual aberrations rather than interpersonal
      difficulties.

PMID- 21741635
TI  - A sub-space greedy search method for efficient Bayesian Network inference.
AB  - Bayesian network (BN) has been successfully used to infer the regulatory
      relationships of genes from microarray dataset. However, one major limitation of
      BN approach is the computational cost because the calculation time grows more
      than exponentially with the dimension of the dataset. In this paper, we propose a
      sub-space greedy search method for efficient Bayesian Network inference.
      Particularly, this method limits the greedy search space by only selecting gene
      pairs with higher partial correlation coefficients. Using both synthetic and real
      data, we demonstrate that the proposed method achieved comparable results with
      standard greedy search method yet saved ~50% of the computational time. We
      believe that sub-space search method can be widely used for efficient BN
      inference in systems biology.

PMID- 21741636
TI  - Structural plasticity of the left caudate in bimodal bilinguals.
AB  - Bilinguals need an effective neural mechanism to select and control their
      languages for successful communication. Recent evidence indicates that the left
      caudate nucleus (LCN) is a critical part of this mechanism. Here we show that
      bimodal bilinguals, who use spoken and sign languages, have greater grey matter
      volume (GMV) in the head of the LCN as compared to monolinguals. We also found
      higher functional activation of this region in bimodal bilinguals when they
      switched between sign language and spoken language compared to when they did not
      switch languages. Furthermore, GMV was positively correlated with the magnitude
      of the switching effect in the head of the LCN. These findings indicate that for
      bimodal bilinguals, the LCN is shaped by bilingualism both anatomically and
      functionally.

PMID- 21741637
TI  - Transcriptional modulation of a human monocytic cell line exposed to PM(10) from
      an urban area.
AB  - Insight into the mechanisms by which ambient air particulate matter mediates
      adverse health effects is needed to provide biological plausibility to
      epidemiological studies demonstrating an association between PM(10) exposure and
      increased morbidity and mortality. In vitro studies of the effects of air
      pollution on human cells help to establish conditions for the analysis of cause
      effect relationships. One of the major challenges is to test native atmosphere in
      its complexity, rather than the various components individually. We have
      developed an in vitro system in which human monocyte-macrophage U937 cells are
      directly exposed to filters containing different amounts of PM(10) collected in
      the city of Rome. Transcriptional profiling obtained after short exposure (1h) of
      cells to a filter containing 1666MUg PM(10) (77.6MUg/cm(2)) using a macroarray
      panel of 1176 genes reveals a significant change in the mRNA level (>2 fold) for
      87 genes relative to cells exposed to a control filter. Overall, 9 out of 87
      modulated genes were annotated as "lung cancer". qRT-PCR confirmed the induction
      of relevant genes involved in DNA repair and apoptosis, specifically: ERCC1, TDG,
      DAD1 and MCL1. In cells exposed for 10min, 1h and 3h to different amounts of
      PM(10), transcription of TNFalpha and TRAP1, which code for a key pro
      inflammatory cytokine and a mitochondrial protein involved in cell protection
      from oxidative stress, respectively, was shown to be modulated in a time
      dependent, but not a dose-dependent manner. Taken together, these data indicate
      that it is possible to analyze the effects of untreated particulate matter on
      human cells by the direct-exposure approach we have developed, possibly providing
      new clues to traffic-related health hazard.

PMID- 21741638
TI  - Complete endoscopic removal of a necrotic spleen (with video).

PMID- 21741639
TI  - Endoscopy for upper GI cancer screening in the general population: a cost-utility
      analysis.
AB  - BACKGROUND: Colon cancer screening with colonoscopy is an accepted strategy;
      however, there are limited data regarding the cost-effectiveness of screening for
      upper GI cancers (esophageal adenocarcinoma with its premalignant precursor
      Barrett's esophagus, esophageal squamous cell cancer, gastric adenocarcinoma) in
      the United States. OBJECTIVE: To evaluate the cost-effectiveness of screening the
      general population for upper GI cancers by performing an upper endoscopy at the
      time of screening colonoscopy. DESIGN: Decision analysis. SETTING: Third-party
      payer perspective with a time horizon of 30 years or until death. PATIENTS: This
      study involved 50-year-old patients already undergoing screening colonoscopy.
      INTERVENTION: Comparison of two strategies: performing and not performing a
      screening upper endoscopy at the time of screening colonoscopy. MAIN OUTCOME
      MEASUREMENTS: Incremental cost-effectiveness ratio (ICER). RESULTS: One-time
      screening for the general population at the age of 50 for upper GI cancers
      required $115,664 per quality-adjusted life year (QALY) compared with no
      screening or surveillance. A strategy of screening and surveillance for Barrett's
      esophagus required only $95,559 per QALY saved. In 1-way sensitivity analyses,
      the prevalence rates of esophageal adenocarcinoma, esophageal squamous cell
      cancer, or gastric adenocarcinoma would have to increase by 654%, 1948%, and
      337%, respectively, to generate an ICER of less than $50,000 per QALY.
      LIMITATIONS: Omission of premalignant conditions for squamous cell cancer and
      gastric adenocarcinoma. CONCLUSION: The ICER for screening the general population
      for upper GI cancers with endoscopy remains high, despite accounting for reduced
      endoscopy costs and the combined benefits of detecting early esophageal
      adenocarcinoma, esophageal squamous cell cancer, and gastric adenocarcinoma.
      However, the ICER compares favorably with commonly performed screening strategies
      for other cancers.

PMID- 21741640
TI  - Localized autoimmune pancreatitis, 9 mm in size, without strictures of the main
      pancreatic duct.

PMID- 21741641
TI  - A new technique for endoscopic removal of uncovered biliary self-expandable metal
      stents: stent-in-stent technique with a fully covered biliary stent.

PMID- 21741642
TI  - Real-time increased detection of neoplastic tissue in Barrett's esophagus with
      probe-based confocal laser endomicroscopy: final results of an international
      multicenter, prospective, randomized, controlled trial.
AB  - BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) allows real-time
      detection of neoplastic Barrett's esophagus (BE) tissue. However, the accuracy of
      pCLE in real time has not yet been extensively evaluated. OBJECTIVE: To compare
      the sensitivity and specificity of pCLE in addition to high-definition white
      light endoscopy (HD-WLE) with HD-WLE alone for the detection of high-grade
      dysplasia (HGD) and early carcinoma (EC) in BE. DESIGN: International,
      prospective, multicenter, randomized, controlled trial. SETTING: Five tertiary
      referral centers. PATIENTS: A total of 101 consecutive BE patients presenting for
      surveillance or endoscopic treatment of HGD/EC. INTERVENTIONS: All patients were
      examined by HD-WLE, narrow-band imaging (NBI), and pCLE, and the findings were
      recorded before biopsy samples were obtained. The order of HD-WLE and NBI was
      randomized and performed by 2 independent, blinded endoscopists. All suspicious
      lesions on HD-WLE or NBI and 4-quadrant random locations were documented. These
      locations were examined by pCLE, and a presumptive diagnosis of benign or
      neoplastic (HGD/EC) tissue was made in real time. Finally, biopsies were taken
      from all locations and were reviewed by a central pathologist, blinded to
      endoscopic and pCLE data. MAIN OUTCOME MEASUREMENTS: Diagnostic characteristics
      of pCLE. RESULTS: The sensitivity and specificity for HD-WLE were 34.2% and
      92.7%, respectively, compared with 68.3% and 87.8%, respectively, for HD-WLE or
      pCLE (P = .002 and P < .001, respectively). The sensitivity and specificity for
      HD-WLE or NBI were 45.0% and 88.2%, respectively, compared with 75.8% and 84.2%,
      respectively, for HD-WLE, NBI, or pCLE (P = .01 and P = .02, respectively). Use
      of pCLE in conjunction with HD-WLE and NBI enabled the identification of 2 and 1
      additional HGD/EC patients compared with HD-WLE and HD-WLE or NBI, respectively,
      resulting in detection of all HGD/EC patients, although not statistically
      significant. LIMITATIONS: Academic centers with enriched population. CONCLUSIONS:
      pCLE combined with HD-WLE significantly improved the ability to detect neoplasia
      in BE patients compared with HD-WLE. This may allow better informed decisions to
      be made for the management and subsequent treatment of BE patients. ( CLINICAL
      TRIAL REGISTRATION NUMBER: NCT00795184.).

PMID- 21741643
TI  - Can we improve adenoma detection rates? A systematic review of intervention
      studies.

PMID- 21741644
TI  - One-step endoscopic treatment of dysphagia in patients with vertical banded
      gastroplasty stenosis by complete transgastric cutting: first experience with two
      patients (with video).

PMID- 21741645
TI  - Endoscopic and oncologic outcomes after endoscopic resection for early gastric
      cancer: 1370 cases of absolute and extended indications.
AB  - BACKGROUND: Current guidelines for endoscopic management such as EMR and
      endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) are in
      evolution, with broader indication criteria. OBJECTIVE: To determine the clinical
      outcomes of endoscopic treatment, based on absolute indication and extended
      indication criteria and endoscopic methods. DESIGN: Retrospective study. SETTING:
      Tertiary-care, academic medical center. PATIENTS: EMR or ESD was performed on
      1627 cases of EGC in 1447 patients from July 1994 to January 2009. INTERVENTION:
      EMR and ESD. MAIN OUTCOME MEASUREMENTS: Clinical outcomes of EGC after EMR or
      ESD, based on the indication criteria. RESULTS: Although the complete resection
      rate was higher (95.9% vs 88.4%; P < .001), and the complication rate was lower
      (6.8% vs 9.8%; P = .054) in the absolute than in the extended indication group,
      there was no between-group difference in the local recurrence rate (0.9% vs 1.1%;
      P = .783) at a median follow-up period of 32 months (interquartile range 22-48
      months). In the extended indication group, ESD resulted in a significantly higher
      complete resection rate than EMR (83.0% vs 91.1%; P = .006). LIMITATIONS:
      Retrospective study. CONCLUSION: ESD in the extended indication group showed
      acceptable clinical outcomes with a relatively high complete resection rate and a
      low local recurrence rate.

PMID- 21741646
TI  - Pachyosteosclerosis suggests archaic Homo frequently collected sessile littoral
      foods.
AB  - Fossil skeletons of Homo erectus and related specimens typically had heavy
      cranial and postcranial bones, and it has been hypothesised that these represent
      adaptations, or are responses, to various physical activities such as endurance
      running, heavy exertion, and/or aggressive behavior. According to the comparative
      biological data, however, skeletons that show a combination of disproportionally
      large diameters, extremely compact bone cortex, and very narrow medullary canals
      are associated with aquatic or semi-aquatic tetrapods that wade, and/or dive for
      sessile foods such as hard-shelled invertebrates in shallow waters. These so
      called pachyosteosclerotic bones are less supple and more brittle than non
      pachyosteosclerotic bones, and marine biologists agree that they function as
      hydrostatic ballast for buoyancy control. This paper discusses the possibility
      that heavy skeletons in archaic Homo might be associated with part-time
      collection of sessile foods in shallow waters.

PMID- 21741647
TI  - Facial soft tissue thickness in individuals with different occlusion patterns in
      adult Turkish subjects.
AB  - Knowledge of variation in facial soft tissue thickness is important for forensic
      anthropologists, dentists, and plastic surgeons. Forensic anthropologists use
      such information as a guide in facial reconstruction and superimposition methods.
      The purpose of this study was to measure facial tissue thicknesses of adult males
      and females of Turkish origin across different types of occlusion, and to compare
      the results with each other and with values obtained for other populations. The
      study was conducted on 200 healthy individuals. The analysis of facial tissue
      thickness included 20 landmarks (10 dentoskeletal and 10 soft tissue) and 10
      linear variables. Sex-based variation in facial tissue thickness was noted. The
      highest soft tissue thickness values were observed in the group with Class III
      occlusion type at Sn-A point for both the females (16.9, SD=2.4) and the males
      (17.8, SD=3.3). In the Class I group, the highest tissue depth was observed at Sn
      A point (15.3, SD=2.1) in females, and at Li-Id point (17.1, SD=1.9) in males. In
      the Class II group, contrary to the findings for Class I, the highest soft tissue
      depth was at Li-Id point (16.0, SD=1.4) in females, and at Sn-A point (18.1,
      SD=2.6) in males. In conclusion, facial tissue thickness varied in adults
      depending on the sex and on the type of occlusion.

PMID- 21741648
TI  - Hinfinity synchronization of uncertain fractional order chaotic systems: adaptive
      fuzzy approach.
AB  - This paper presents a novel adaptive fuzzy logic controller (FLC) equipped with
      an adaptive algorithm to achieve H(infinity) synchronization performance for
      uncertain fractional order chaotic systems. In order to handle the high level of
      uncertainties and noisy training data, a desired synchronization error can be
      attenuated to a prescribed level by incorporating fuzzy control design and
      H(infinity) tracking approach. Based on a Lyapunov stability criterion, not only
      the performance of the proposed method is satisfying with an acceptable
      synchronization error level, but also a rather simple stability analysis is
      performed. The simulation results signify the effectiveness of the proposed
      control scheme.

PMID- 21741649
TI  - AIS>2 in at least two body regions: a potential new anatomical definition of
      polytrauma.
AB  - BACKGROUND: The term 'polytrauma' lacks a universally accepted, validated
      definition. In clinical trials the commonly applied injury severity based
      anatomical score cut-offs are ISS > 15, ISS > 17 and a recently recommended AIS >
      2 in at least two body regions (2 * AIS > 2). PURPOSE: To compare the outcomes of
      clinically defined polytrauma patients with those defined based on anatomical
      scores. MATERIAL AND METHODS: A prospective observational study on all trauma
      team activation patients over a 7-month period presenting at a level-1 trauma
      centre were included in the study. The prospective data collection included AIS
      in each body region, ISS, ICU length of stay (LOS), multiple organ failure (MOF)
      and mortality. RESULTS: 336 patients met inclusion criteria (age: 41 +/- 20, 74%
      male, ISS: 15 +/- 11, NISS: 19 +/- 15, MOF: 3%, mortality: 4%, 25% ICU
      admission). ISS > 15: 13 deaths (10%), 71 (54%) required ICU admission and 10
      (8%) developed MOF. ISS > 17 captured 11 deaths (11%), with 63 (62%) requiring
      ICU admission and 10 (10%) developing MOF. Defining as (2 * AIS > 2): 8 deaths
      (13% of the group), with 43 patients requiring ICU admission (67%) and 9 (14%)
      developing MOF. When examining the performance of these three approaches, the ISS
      > 15 and the ISS > 17 captured statistically the same amount of clinically
      defined polytrauma patients (p = 0.4106), while the 2 * AIS > 2 definition
      captured significantly more polytrauma patients than ISS > 15 (p = 0.0251) and
      ISS > 17 (p = 0.0019). CONCLUSION: 2 * AIS > 2 captured the greatest percentage
      of the worst outcomes and significantly larger % of the clinically defined
      polytrauma patients. 2 * AIS > 2 has higher accuracy and precision in defining
      polytrauma than ISS > 15 and ISS > 17. This simple, retrospectively also
      reproducible criteria warrants larger scale validation.

PMID- 21741650
TI  - Diagnostic and treatment modalities in nonunions of the femoral shaft: a review.
AB  - Nonunions of the femoral shaft represent a treatment challenge for the
      orthopaedic surgeon and a serious socioeconomic problem for the patient.
      Inadequate fracture stability, insufficient blood supply, bone loss or presence
      of infection are the main reasons for the development of a nonunion. Careful
      classification and exclusion of infection are crucial for the choice of the
      proper treatment alternative. Nail dynamization, primary intramedullary nailing
      or nail exchange, plate osteosynthesis and external fixation along with bone
      grafting, usage of bone substitutes and electrical stimulation can stimulate
      osseous union. A review of the aetiology, classification and treatment should
      prove helpful managing this serious complication.

PMID- 21741651
TI  - Non-uniform shrinkage for obtaining computational start shape for in-vivo MRI
      based plaque vulnerability assessment.
AB  - BACKGROUND: Critical mechanical conditions, such as stress within the structure
      and shear stress due to blood flow, predicted from in-vivo magnetic resonance
      image (MRI)-based computational simulations have shown to be potential in
      assessing carotid plaque vulnerability. Plaque contours obtained from in-vivo MRI
      are a result of a pressurized configuration due to physiological loading.
      However, in order to make accurate predictions, the computational model must be
      based on the loading-free geometry. A shrinkage procedure can be used to obtain
      the computational start shape. METHOD: In this study, electrocardiograph (ECG)
      gated MR-images of carotid plaques were obtained from 28 patients. The contours
      of each plaque were segmented manually. Additional to a uniform shrinkage
      procedure, a non-uniform shrinkage refinement procedure was used. This procedure
      was repeated until the pressurized lumen contour and fibrous cap thickness had
      the best match with the in-vivo image. RESULTS: Compared to the uniform shrinkage
      procedure, the non-uniform shrinkage significantly reduced the difference in
      lumen shape and in cap thickness at the thinnest site. Results indicate that
      uniform shrinkage would underestimate the critical stress in the structure by
      20.5+/-10.7%. CONCLUSION: For slices with an irregular lumen shape (the ratio of
      the maximum width to the minimum width is more than 1.05), the non-uniform
      shrinkage procedure is needed to get an accurate stress profile for mechanics and
      MRI-based carotid plaque vulnerability assessment.

PMID- 21741652
TI  - Methodology for porting retention prediction data from old to new columns and
      from conventional-scale to miniaturised ion chromatography systems.
AB  - Several procedures are available for simulating and optimising separations in ion
      chromatography (IC), based on the application of retention models to an extensive
      database of analyte retention times on a wide range of columns. These procedures
      are subject to errors arising from batch-to-batch variability in the synthesis of
      stationary phases, or when using a column having a different diameter to that
      used when the database was acquired originally. Approaches are described in which
      the retention database can be recalibrated to accommodate changes in the
      stationary phase (ion-exchange selectivity coefficient and ion-exchange capacity)
      or in the column diameter which lead to changes in phase ratio. The entire
      database can be recalibrated for all analytes on a particular column by
      performing three isocratic separations with two analyte ions. The retention data
      so obtained are then used to derive a "porting" equation which is employed to
      generate the required simulated separation. Accurate prediction of retention
      times is demonstrated for both anions and cations on 2mm and 0.4mm diameter
      columns under elution conditions which consist of up to five sequential isocratic
      or linear gradient elution steps. The proposed approach gives average errors in
      retention time prediction of less than 3% and the correlation coefficient was
      0.9849 between predicted and observed retention times for 344 data points
      comprising 33 anionic or cationic analytes, 5 column internal diameters and 8
      complex elution profiles.

PMID- 21741653
TI  - Size separation of colloidally dispersed nanoparticles using a monolithic
      capillary column.
AB  - We developed a method to separate colloidally dispersed nanoparticles on
      monolithic capillary columns. Silica nanoparticles were eluted according to their
      sizes, and the plots of the logarithm of the size of nanoparticles against their
      elution volume showed good linearity (r=0.992) over wide range of sizes. Because
      of the high porosity of the monolithic column (porosity; 88%), the column's
      length could be increased without clogging of the dispersed samples and the
      pressure in a long column (500 mm * 0.2 mm i.d.) was low, with a value of 5.8 MPa
      at a flow rate of 1 MUL/min. We demonstrate that this method using monolithic
      capillary columns could be used as a powerful tool for size separation of
      nanometer-size materials, which will open a new pathway to quality control of
      nanomaterials in nanotechnology applications.

PMID- 21741654
TI  - Ruggedness and robustness of conversion factors in method of simultaneous
      determination of multi-components with single reference standard.
AB  - Single standard to determine multi-components (SSDMC) is a novel and rational
      method for quality control of botanical products and traditional Chinese
      medicines (TCMs). However, it is restricted to wide application due to unknown
      fluctuation in conversion factors when it is performed in different laboratories.
      To evaluate the fluctuations of conversion factors, we selected Salvia
      miltiorrhiza as an example to determine three components of tanshinones by SSDMC
      method. Then ruggedness and robustness test were adopted to comprehensively
      investigate three kinds of factors that may influence stability of conversion
      factors, which were related with environmental parametric variables, operational
      parametric variables and peak measurement parametric variables. Nested-factorial
      design was used to perform ruggedness tests. One-variable-at-a-time (OVAT)
      procedure and Plackett-Burman (PB) design were both used in robustness test. The
      results showed that stability of conversion factors was principally related with
      accuracy of wavelength of UV detector, peak measurement parameters and
      concentration of standard solution. The acceptable range of conversion factors
      was obtained from robustness test. Our results showed that conversion factors
      were inevitable to change, but when key parameters were well controlled, the
      range of its fluctuation was acceptable and the SSDMC method could be used widely
      in different laboratories.

PMID- 21741655
TI  - Identification of potent odourants in wine and brewed coffee using gas
      chromatography-olfactometry and comprehensive two-dimensional gas chromatography.
AB  - Volatile constituents in wine and brewed coffee were analyzed using a combined
      system incorporating both GC-olfactometry (GC-O) and comprehensive two
      dimensional GC-flame ionization detection (GC*GC-FID). A column set consisting of
      a 15m first dimension ((1)D; DB-FFAP (free fatty acid phase)), and a 1.0m (2)D
      column (DB-5 phase) was applied to achieve the GC*GC separation of the volatile
      extracts isolated by using solid phase extraction (SPE). While 1D GC resulted in
      many overlapping peaks, GC*GC allowed resolution of co-eluting compounds which
      coincided with the odour region located using GC-O. Character-impact odourants
      were tentatively identified through data correlation of GC*GC contour plots
      across results obtained using either time-of-flight mass spectrometry (TOFMS), or
      with flame photometric detection (FPD) for sulfur speciation. The odourants 2
      methyl-2-butenal, 2-(methoxymethyl)-furan, dimethyl trisulfide, 2-ethyl-5-methyl
      pyrazine, 2-octenal, 2-furancarboxaldehyde, 3-mercapto-3-methyl-1-butanol, 2
      methoxy-3-(2-methylpropyl)-pyrazine, 2-furanmethanol and isovaleric acid were
      suspected to be particularly responsible for coffee aroma using this approach.
      The presented methodology was applied to identify the potent odourants in two
      different Australian wine varietals. 1-Octen-3-ol, butanoic acid and 2
      methylbutanoic acid were detected in both Merlot and a Sauvignon Blanc+Semillon
      (SV) blend with high aroma potency. Several co-eluting peaks of ethyl 4-oxo
      pentanoate, 3,7-dimethyl-1,5,7-octatrien-3-ol, (Z)-2-octen-1-ol, 5-hydroxy-2
      methyl-1,3-dioxane were likely contributors to the Merlot wine aroma; while (Z)-3
      hexen-1-ol, beta-phenylethyl acetate, hexanoic acid and co-eluting peaks of 3
      ethoxy-1-propanol and hexyl formate may contribute to SV wine aroma character.
      The volatile sulfur compound 2-mercapto-ethyl acetate was believed to contribute
      a fruity, brothy, meaty, sulfur odour to Australian Merlot and SV wines.

PMID- 21741656
TI  - Steric effects on the enantiodiscrimination of diproline chiral stationary phases
      in the resolution of racemic compounds.
AB  - Eight diproline chiral stationary phases with different end-capping groups were
      prepared and evaluated for the enantio-selective resolution of 41 racemic
      analytes. The end-capping group on the N-terminal of the peptide proved to be
      important as the chiral separation efficiency was decreased significantly without
      it. In general, increasing steric bulkiness near the N-terminal of diproline
      increases the enantioselectivity. Electronic structures of the end-capping groups
      are also important. One stationary phase with an adamantanecarbonyl capping group
      was found to provide both higher average separation and resolution factors than
      our previous leader. Three other stationary phases with 2-methylpropanoyl,
      cyclopropanecarbonyl and cyclobutanecarbonyl end capping groups were found to
      provide comparable average separation factor but higher resolution factors than
      our previous leader.

PMID- 21741657
TI  - Modifying the surface of Fe3O4/SiO2 magnetic nanoparticles with C18/NH2 mixed
      group to get an efficient sorbent for anionic organic pollutants.
AB  - In this article, C(18)/NH(2) mixed group modified Fe(3)O(4)/SiO(2) magnetic
      nanoparticles (Fe(3)O(4)/SiO(2)/C(18)+NH(2) MNPs) were successfully synthesized
      and used for the extraction of perfluorinated compounds (PFCs) from large volume
      of water solution. The Fe(3)O(4)/SiO(2)/C(18)+NH(2) MNPs, about 25 nm in
      diameter, possess high extraction ability to the anionic organic pollutants due
      to the dual function of hydrophobic octadecyl group and cationic aminopropyl
      groups at low pH. More than 90% of the targets can be extracted from 500 mL of
      water solution with 0.1g of the MNP sorbent at pH 3. Twenty min is sufficient to
      reach adsorption equilibrium, and the targets can be desorbed from the sorbent
      readily with 12 mL of alkalized methanol after magnetic separation. Simplified
      extraction procedure could be achieved because of the superparamagnetism and high
      saturation magnetization of the sorbent (44 emu g(-1)). Therefore,
      preconcentration of trace level of PFCs from water solution can be performed by
      using this Fe(3)O(4)/SiO(2)/C(18)+NH(2) MNP sorbent which are stable for multiple
      reuses.

PMID- 21741658
TI  - Photochromism-based detection of volatile organic compounds by W-doped TiO2
      nanofibers.
AB  - W-doped TiO(2) nanofibers with various compositions (W/Ti: 2-8%) were fabricated
      by the electrospinning method from respective precursor solutions containing
      tungsten(V) pentaethoxide, titanium tetraisopropoxide (TTIP), and
      polyvinylpyrrolidone (PVP), followed with calcination at 550  degrees C.
      Morphological and structural characteristics of these nanofibers were studied
      with SEM, XRD and XPS. W-doping inhibited the crystal growth and anatase-to
      rutile transformation of TiO(2) nanofibers. W-doped TiO(2) nanofiber mats showed
      good photocatalytic oxidation abilities for acetone. Obvious color change from
      white to blue of mats during the photocatalysis process can be detected by naked
      eyes, which provides a good way in detection of pollutants in indoor air,
      especially for the volatile organic compounds (VOCs).

PMID- 21741659
TI  - In situ photoexcitation of silver-doped titania nanopowders for activity against
      bacteria and yeasts.
AB  - Photocatalytic and in situ microbial activity of the amorphous and annealed
      states of Ag-doped and un-doped titania were examined. Studies on their
      structure, morphology, composition, and the photo-absorption characteristics of
      these materials were performed. These results were correlated with the
      photocatalytic and microbial activity against methicillin resistant
      Staphylococcus aureus K324 (MRSA), methicillin susceptible S. aureus ATCC 25923
      (MSSA), Escherichia coli PA 170, and yeasts Candida albicans ATCC 90028. The
      annealed powders containing anatase form of titania exhibited relatively higher
      photocatalytic activity,corresponding to activity against MRSA,when exposed to UV
      A radiation. In comparison, amorphous powders exhibited low photoactivity and
      showed poor antibacterial performance against MRSA under UV-A exposure. Doping of
      amorphous titania with Ag resulted in an anti-MRSA effect without exposure to UV
      radiation. In the Ag-doped crystalline anatase samples, the size of Ag primary
      nanocrystallites increased, which led to the decrease in the surface
      concentration of Ag and detriment anti-MRSA activity.

PMID- 21741660
TI  - Potential applications of the new ECGSIM.
AB  - This contribution demonstrates some applications of the most recent release of
      ECGSIM, an interactive simulation program that enables the user to study the
      relationship between the electric current sources of the heart and the resulting
      electrocardiographic signals on the body surface as well as those on the surface
      of the heart. It aims to serve as an educational tool as well as a research tool.
      The examples are drawn from the topics discussed by the participants of the
      Magnetic Anatomic and eLectrical Technology meeting in Maastricht, the
      Netherlands (February 2011), reports of which are to be found in the current
      issue of the Journal of Electrocardiology. These examples include simulation of
      the atrial electrocardiogram, improved accessibility of endocardial source
      locations, and an explanation of ST elevations accompanying true TQ depressions.

PMID- 21741661
TI  - Cardiac magnetic resonance imaging as a tool to link cardiac conduction disease
      to myocarditis with minimal left ventricular impairment.
AB  - Myocarditis is an injury of the myocardium caused by a variety of agents.
      Conduction disturbances such as complete atrioventricular block (AV block) may
      occur as an infrequent but serious complication of myocarditis. Early detection
      and accurate diagnosis of myocarditis are still unresolved challenges. We present
      2 cases of otherwise mild myocarditis complicated by high-degree AV block in
      combination with isolated delayed uptake of contrast at the septal regions in the
      cardiac magnetic resonance imaging. Because the AV block was persistent in both
      cases, permanent pacemaker implantation was necessary. Delayed enhancement in the
      septal area in myocarditis might be predictive of infra-Hisian AV block.

PMID- 21741662
TI  - Lymphocyte adhesion to CCR5 ligands is reduced by anti-CCR5 gene delivery.
AB  - Immune-mediated damage to the central nervous system (CNS) is an important
      contributor to many CNS diseases, including epilepsy. Chemokines play a role in
      leukocyte recruitment to, and migration across, the blood-brain barrier (BBB)
      during many such processes. We previously investigated the role of the chemokine
      receptor CCR5 in a rat model of epilepsy based on intraperitoneal kainic acid
      (KA) administration. Before KA injection, rats were given intramarrow
      inoculations of SV(RNAiR5-RevM10.AU1), which carries an interfering RNA (RNAi)
      that targets CCR5. Decreased CCR5 expression in blood cells after vector
      administration reduced expression of CCR5 ligands MIP-1alpha and RANTES in the
      microvasculature, and strongly protected from BBB leakage, CNS loss and
      inflammation and facilitated CNS repair. We show here that rSV40-mediated
      downregulation of CCR5 in lymphocytes decreased cellular adhesion to surfaces
      carrying CCR5 ligands. These data suggest that reducing CCR5 in peripheral blood
      mononuclear cells (PBMCs) might alter their adhesion to the microvasculature and
      their participation in inflammatory processes.

PMID- 21741663
TI  - Subjective emotional experience at different stages of Parkinson's disease.
AB  - Subjective emotional experience is thought to rely on a large cortical
      subcortical network including orbitofrontal and cingulate frontostriatal circuits
      together with the mesolimbic dopaminergic system that modulates their activity.
      Parkinson's disease (PD) provides a model for exploring this issue. By using an
      original emotion induction procedure, the present study examined to what extent
      subjective experience of emotion of PD patients at different stages of the
      disease was modulated by emotion in the same way as healthy individuals. A
      battery of film excerpts was used to elicit different emotional feelings
      (happiness, anger, fear, sadness, disgust, and neutral) in 15 newly diagnosed PD
      patients, 18 patients with advanced PD and 15 matched controls. The newly
      diagnosed patients were examined in two conditions: "on" and "off" dopaminergic
      medication. Participants reported the intensity of their emotional feelings on a
      scale consisting of 10 emotional categories. Results indicated that PD patients
      at different stages of the disease did not significantly differ from the controls
      in the self-reported emotional experience to the presented film excerpts.
      Moreover, analyses conducted within the newly diagnosed PD group (on-dopa vs. off
      dopa conditions) indicated that the patients' emotional reactivity to the
      presented film excerpts was not significantly modulated by dopaminergic
      medication. These results thus question the possible role of dopaminergic
      pathways in subjective emotional experience, at least in this sample and in the
      context of emotion induction.

PMID- 21741664
TI  - HLA associations with multiple sclerosis in Greece.
AB  - BACKGROUND: Multiple sclerosis (MS) is a demyelinating inflammatory disease of
      the central nervous system originated by a complex interplay of environmental and
      genetic factors. The association of MS with the human leukocyte antigen (HLA)
      class II alleles was investigated in MS patients in northwest Greece, in the
      geographical region of Epirus. OBJECTIVE: Our aim was to estimate the prevalence
      of the HLA-DRB1*1501, HLA-DQB1*0602 and HLA-DQA1*0102 alleles, consisting the
      most common susceptibility haplotype in North European and North American
      Caucasians. METHODS: We studied 126 MS patients and 93 age and sex matched
      healthy controls. HLA typing was performed by a polymerase chain reaction (PCR)
      amplification with sequence-specific primers (PCR-SSP) method. RESULTS: We found
      that HLA-DRB1*1501, HLA-DQB1*0602 and HLA-DQA1*0102 alleles were significantly
      more frequent among patients (34% versus 11%, p=0.00015; 69% versus 51%, p=0.01;
      76% versus 55%, p=0.002, respectively). HLA-DRB1*1501, HLA-DQB1*0602, HLA
      DQA1*0102 haplotype was significantly more common among patients (p=0.00067). HLA
      DRB1*1501 and HLA-DQB1*0602 alleles were more frequently detected in patients
      with initial symptoms from the brainstem or the cerebellum (p=0.024). No
      significant correlation was observed among these alleles with sex, disease
      clinical course, or age at onset. CONCLUSION: This is the first study to
      investigate genetic susceptibility to MS in Greece. Our results are in line with
      previous reports in North European and North American patients.

PMID- 21741665
TI  - The MTHFD1L gene rs11754661 marker is associated with susceptibility to
      Alzheimer's disease in the Chinese Han population.
AB  - Our objective is to evaluate the relationship between the rs11754661 polymorphism
      of the MTHFD1L gene and Alzheimer's disease (AD) in the ethnic Chinese Han. We
      conducted a case-control study (n=380, age>50) to determine the prevalence of one
      common single-nucleotide polymorphism (SNP) of MTHFD1L (rs11754661) in patients
      with AD in Chinese population of Mainland China, and clarified whether this
      polymorphism is a risk factor for AD. The prevalence of the minor allele (A) in
      the rs11754661 polymorphism was significantly different in AD patients and
      control subjects (P<0.01). The rs11754661 polymorphism was associated with AD in
      the ethnic Chinese Han (OR=1.829, 95% CI: 1.277-2.619, P=0.001), and the results
      were influenced by APOE status. Our data revealed that the allele (A) of the
      rs11754661 polymorphism within MTHFD1L gene may contribute to AD risk in the
      Chinese Han population.

PMID- 21741666
TI  - Responses of four Indo-West Pacific seagrass species to shading.
AB  - Seagrasses of the Great Barrier Reef predominantly occur in coastal regions where
      terrestrial inputs modify water quality and photosynthetic light is highly
      variable. Responses to shading were tested for Cymodocea serrulata, Halodule
      uninervis, Thalassia hemprichii and Zostera muelleri. In aquaria, four light
      treatments - high (66% surface light), moderate (31%), low (14%) and very low
      light (1%) treatments - were applied for 102d. Stress responses in the low and
      very low light treatments occurred in the following sequence: metabolic and
      physiological changes (reduced growth, increased pigment concentrations and
      photosynthetic efficiency); shedding (leaf loss, shoot loss) and production of
      new, altered tissue (leaves with reduced length, width and thickness). Complete
      shoot loss was projected after 76 (Z. muelleri) to 130d (T. hemprichii).
      Responses were slower in the low than in the very low treatment, therefore,
      efforts to minimize water quality degradation will be rewarded with delayed
      impacts to seagrasses.

PMID- 21741667
TI  - Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3.
AB  - The alphaherpesvirus serine/threonine kinase Us3 plays diverse roles in virus
      multiplication and modifies both nuclear and cytoplasmic substrates. We recently
      reported that treatment of HSV-2 Us3-transfected and HSV-2-infected cells with
      leptomycin B, an inhibitor of nuclear export mediated by interaction of
      chromosomal regional maintenance protein (CRM1) with leucine rich nuclear export
      signals (NESs), resulted in nuclear trapping of Us3. Here, we utilized
      fluorescence loss in photobleaching to monitor nuclear export of HSV-2 Us3 and
      confirm that this process proceeds solely via a CRM1-mediated mechanism. Analysis
      of deletion derivatives of HSV-2 Us3 fused to a nuclear export reporter protein
      implicated the involvement of NES-like sequences in nuclear export. However,
      nuclear trapping of HSV-2 Us3 proteins carrying mutations in these potential NESs
      was not observed, indicating that these sequences are not functional in the
      context of full-length protein. Our analyses also revealed previously
      unidentified regions of HSV-2 Us3 that contribute to its kinase activity.

PMID- 21741668
TI  - Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV
      DNA polymerase processivity factor ppUL44.
AB  - The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein
      ppUL44, is essential for viral replication. During viral infection ppUL44 is
      phosphorylated by the viral kinase pUL97, but neither the target residues on
      ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We
      report here that ppUL44 is phosphorylated when transiently expressed in mammalian
      cells and coimmunoprecipitates with cellular kinases. Of three potential
      phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear
      localization signal (NLS) and one (T427) within the NLS itself, protein kinase
      CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of
      phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at
      the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of
      ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1
      phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear
      transport of ppUL44 is finely tuned during viral infection through complex
      phosphorylation events.

PMID- 21741669
TI  - Intrinsic biodegradation potential of aromatic hydrocarbons in an alluvial
      aquifer--potentials and limits of signature metabolite analysis and two stable
      isotope-based techniques.
AB  - Three independent techniques were used to assess the biodegradation of
      monoaromatic hydrocarbons and low-molecular weight polyaromatic hydrocarbons in
      the alluvial aquifer at the site of a former cokery (Flemalle, Belgium). Firstly,
      a stable carbon isotope-based field method allowed quantifying biodegradation of
      monoaromatic compounds in situ and confirmed the degradation of naphthalene. No
      evidence could be deduced from stable isotope shifts for the intrinsic
      biodegradation of larger molecules such as methylnaphthalenes or acenaphthene.
      Secondly, using signature metabolite analysis, various intermediates of the
      anaerobic degradation of (poly-) aromatic and heterocyclic compounds were
      identified. The discovery of a novel metabolite of acenaphthene in groundwater
      samples permitted deeper insights into the anaerobic biodegradation of almost
      persistent environmental contaminants. A third method, microcosm incubations with
      13C-labeled compounds under in situ-like conditions, complemented techniques one
      and two by providing quantitative information on contaminant biodegradation
      independent of molecule size and sorption properties. Thanks to stable isotope
      labels, the sensitivity of this method was much higher compared to classical
      microcosm studies. The 13C-microcosm approach allowed the determination of first
      order rate constants for 13C-labeled benzene, naphthalene, or acenaphthene even
      in cases when degradation activities were only small. The plausibility of the
      third method was checked by comparing 13C-microcosm-derived rates to field
      derived rates of the first approach. Further advantage of the use of 13C-labels
      in microcosms is that novel metabolites can be linked more easily to specific
      mother compounds even in complex systems. This was achieved using alluvial
      sediments where 13C-acenaphthyl methylsuccinate was identified as transformation
      product of the anaerobic degradation of acenaphthene.

PMID- 21741670
TI  - Of microparticles and bacteria identification--(resonance) Raman micro
      spectroscopy as a tool for biofilm analysis.
AB  - Confocal resonance Raman microscopy is a powerful tool for the non-invasive
      analysis of complex biological aggregates without preparation and prior knowledge
      of the samples. We present the capabilities of confocal resonance Raman
      microscopy with a spatial resolution of 350 nm2*2.0 MUm and excitation times of 1
      s and less per recorded spectrum. Granules sampled from two sequencing batch
      reactors (SBR) for anaerobic ammonium oxidization (anammox) were regularly mapped
      in vivo for three months after SBR startup. Uncultured microorganisms and mineral
      particles were tracked throughout operation and identified in situ by their
      (resonance) Raman spectra. Co-existing microcolonies of Nitrosomonae formed the
      outer layer of anammox granules. Polymorph TiO2 microparticles were found
      embedded in the outer layer of granules overgrown with purple bacteria,
      indicating bacterial response to the variant toxicity of the mineral phase.

PMID- 21741671
TI  - Estimating risk at a Superfund site using passive sampling devices as biological
      surrogates in human health risk models.
AB  - Passive sampling devices (PSDs) sequester the freely dissolved fraction of
      lipophilic contaminants, mimicking passive chemical uptake and accumulation by
      biomembranes and lipid tissues. Public Health Assessments that inform the public
      about health risks from exposure to contaminants through consumption of resident
      fish are generally based on tissue data, which can be difficult to obtain and
      requires destructive sampling. The purpose of this study is to apply PSD data in
      a Public Health Assessment to demonstrate that PSDs can be used as a biological
      surrogate to evaluate potential human health risks and elucidate spatio-temporal
      variations in risk. PSDs were used to measure polycyclic aromatic hydrocarbons
      (PAHs) in the Willamette River; upriver, downriver and within the Portland Harbor
      Superfund megasite for 3 years during wet and dry seasons. Based on an existing
      Public Health Assessment for this area, concentrations of PAHs in PSDs were
      substituted for fish tissue concentrations. PSD measured PAH concentrations
      captured the magnitude, range and variability of PAH concentrations reported for
      fish/shellfish from Portland Harbor. Using PSD results in place of fish data
      revealed an unacceptable risk level for cancer in all seasons but no unacceptable
      risk for non-cancer endpoints. Estimated cancer risk varied by several orders of
      magnitude based on season and location. Sites near coal tar contamination
      demonstrated the highest risk, particularly during the dry season and remediation
      activities. Incorporating PSD data into Public Health Assessments provides
      specific spatial and temporal contaminant exposure information that can assist
      public health professionals in evaluating human health risks.

PMID- 21741672
TI  - Sources of PCDD/Fs, non-ortho PCBs and PAHs in sediments of high and low impacted
      transboundary rivers (Belgium-France).
AB  - PAHs, PCDD/Fs and non-ortho PCBs have been assessed in Yser and Upper-Scheldt
      river sediments. Higher contamination levels were observed in the Upper-Scheldt
      sediments: maximum concentrations for the 16 US-EPA PAHs, PCDD/Fs and non-ortho
      PCBs respectively amount to 8.9 mg kg(-1), 12 ng TEQ kg(-1) and 5.1 ng TEQ kg(
      1). Diagnostic PAH ratios in sediments and atmospheric samples suggest that the
      PAH compounds are from pyrolytic origin, more specifically combustion processes.
      The huge consumption of coal in cokes-ovens and smelters and its use for house
      heating in Northern France, although decreasing during the last decades, are in
      support of that suggestion. PCDD/F fingerprints in sediments and deposition
      material indicate that OCDD is the dominant congener. In addition use of
      pentachlorophenol (PCP) in the past led to a minor contribution of PCDD/Fs in our
      sediment samples. Non-ortho PCBs form a substantial fraction of the total TEQ
      concentrations observed in the sediments. Since the 1980s and 1990s a substantial
      reduction of the PCDD/F sediment concentrations is observed, but this is not the
      case for the PAHs.

PMID- 21741673
TI  - Assessment of bisphenol A released from reusable plastic, aluminium and stainless
      steel water bottles.
AB  - Bisphenol A (BPA) is a ubiquitous high volume industrial chemical that is an
      estrogen and an environmental endocrine disrupting chemical. Bisphenol A is used
      extensively in the production of consumer goods, polycarbonate plastics, epoxy
      resins and coatings used to line metallic food and beverage cans. There is great
      concern regarding the possible harmful effects from exposures that result from
      BPA leaching into foods and beverages from packaging or storage containers. The
      objective of this study was to independently assess whether BPA contamination of
      water was occurring from different types of reusable drinking bottles marketed as
      alternatives to BPA-containing polycarbonate plastics. Using a sensitive and
      quantitative BPA-specific competitive enzyme-linked immunosorbent assay we
      evaluated whether BPA migrated into water stored in polycarbonate or copolyester
      plastic bottles, and different lined or unlined metallic reusable water bottles.
      At room temperature the concentration of BPA migrating from polycarbonate bottles
      ranged from 0.2 to 0.3 mg L-1. Under identical conditions BPA migration from
      aluminium bottles lined with epoxy-based resins was variable depending on
      manufacturer ranging from 0.08 to 1.9 mg L-1. Boiling water significantly
      increased migration of BPA from the epoxy lined bottles. No detectable BPA
      contamination was observed in water stored in bottles made from TritanTM
      copolyester plastic, uncoated stainless steel, or aluminium lined with EcoCareTM.
      The results from this study demonstrate that when used according to
      manufacturers' recommendations reusable water bottles constructed from "BPA-free"
      alternative materials are suitable for consumption of beverages free of BPA
      contamination.

PMID- 21741674
TI  - Whole-body autoradiography: an efficient technique to study copper accumulation
      and body distribution in small organisms.
AB  - Copepods have been widely used to evaluate toxicity of metals present in marine
      environments. However, a technical difficulty is to understand the possible
      routes of metal uptake and to identify in which tissues or organs metals are
      being accumulated. Traditional techniques are hard to be employed once each organ
      has to be analyzed separately. Autoradiography is an alternative technique to
      circumvent this limitation, since metal distribution in tissues can be visualized
      and quantified, even in small organisms like copepods. In the present study,
      accumulation and distribution of (64)Cu in the copepod Calanus hyperboreus was
      studied using autoradiography. Copepods were exposed for 2 h to copper (2.3 mg L(
      1); 1.08 MBq (64)Cu mg(-1) Cu) and then allowed to depurate for 2 h in clean
      seawater. Total (64)Cu was determined by gamma-spectrometry after a metal
      exposure and a depuration period. (64)Cu distribution was determined based on
      images generated by autoradiography. Metal accumulation was observed on all
      external surfaces of the copepods, being accumulated mostly on the ventral
      region, followed by dorsal, urossoma and internal regions. After depuration,
      radioactivity levels had a decrease in the sum of external body surface. Our
      results show that copper uptake by C. hyperboreus is fast and that a non
      negligible proportion of the accumulated metal can reach internal tissues, which
      may lead to detrimental physiological effects. Moreover, whole-body
      autoradiography was demonstrated to be an efficient technique to study copper
      accumulation and body distribution in a very small organism such as the copepod
      C. hyperboreus.

PMID- 21741675
TI  - Peroxidase-mediated removal of endocrine disrupting compound mixtures from water.
AB  - Several classes of oxidative enzymes have shown promise for efficient removal of
      endocrine disrupting compounds (EDCs) that are resistant to conventional
      wastewater treatments. Although the kinetics of reactions between individual EDCs
      and selected oxidative enzymes are well documented in the literature, there has
      been little investigation of reactions with EDC mixtures. This makes it
      impossible to predict how enzyme-mediated treatment systems will perform since
      wastewater effluents generally contain multiple EDCs. This paper reports pseudo
      first order rate constants for a model oxidative enzyme, horseradish peroxidase
      (HRP), during single-substrate (k1) and mixed-substrate (k1-MIX) reactions.
      Measured values are compared with literature values of three Michaelis-Menten
      parameters: half-saturation constant (KM), enzyme turnover number (kCAT), and the
      ratio kCAT/KM. Published reports had suggested that each of these could be
      correlated with HRP reactivity towards EDCs in mixtures, and empirical results
      from this study show that KM can be used to predict the sequence of EDC removal
      reactions within a particular mixture. We also observed that k1-MIX values were
      generally greater than k1 values and that compounds exhibiting greatest
      estrogenic toxicities reacted most rapidly in a given mixture. Finally, because
      KM may be tedious to measure for every EDC of interest, we have constructed a
      quantitative structure-activity relationship (QSAR) model to predict these
      values. This model predicts KM quite accurately (R2=89%) based on two molecular
      characteristics: molecular volume and hydration energy. Its accuracy makes this
      QSAR a useful tool for predicting which EDCs will be removed most efficiently
      during enzyme treatment of EDC mixtures.

PMID- 21741676
TI  - Antimony pollution in China.
AB  - Antimony (Sb) is ubiquitous throughout the environment as a result of natural
      processes and human activities. In China, superlarge-, large and medium-sized Sb
      deposits are concentrated in the Guangxi (34.4%), Hunan (21.2%), Yunnan (12.2%)
      and Guizhou (10.2%) provinces. Due to Sb mining and smelting processes, large
      quantities of Sb have been released resulting in serious Sb contamination of the
      local environments. Furthermore, coal combustion and Sb products consumed by the
      domestic market are also important potential Sb contamination sources. Here, an
      integrated overview of the current knowledge on the distribution of Sb in Chinese
      environments and the human health risk with respect to Sb contamination in
      Chinese mining and smelting areas are presented. The average Sb concentrations
      found in soils were divided into three groups. Group 1 had lower Sb
      concentrations of 0.5-1.5mgkg(-1), Group 2 had medium concentrations of 1.5
      2mgkg(-1), and Group 3 had relatively high concentrations of over 2mgkg(-1).
      Soils from the Yunnan, Guangxi, Guizhou and Hunan provinces were extremely
      enriched in Sb. Data on the sediment and water mainly came from the Yangtze River
      water systems and some mining and smelting areas. The Sb concentrations in
      sediments were of the order of a few mgkg(-1). In water, Sb was mainly
      concentrated in the particle matter. Higher concentrations in water (up to
      29.4mgL(-1)) and sediments (up to 1163mgkg(-1)) were mainly limited to the
      proximity of mining and smelting areas than the faraway places (<5.00mgL(-1) for
      water and <3.00mgkg(-1) for sediments, respectively). Plants growing in these
      contaminated soils accumulated high levels of Sb (up to 143.7mgkg(-1)) and
      exceeded the tolerable concentration (5mgkg(-1)), thus threatening the health of
      local inhabitants. The local environments around Sb mining and smelting areas
      were seriously contaminated.

PMID- 21741677
TI  - Measurement and scaling of air-surface mercury exchange from substrates in the
      vicinity of two Nevada gold mines.
AB  - The state of Nevada has extensive mineral resources, and is the largest producer
      of gold in the USA as well as fourth in world gold production. Mercury (Hg) is
      often present in the hydrothermal systems that produce gold deposits, and can be
      found in elevated concentrations in gold ore. As a result, mining of gold ore in
      Nevada has been shown to release Hg to the atmosphere from point and non-point
      sources. This project focused on measurement of air-soil Hg exchange associated
      with undisturbed soils and bedrock outcrops in the vicinity of two large gold
      mines. Field and laboratory data collected were used to identify the important
      variables controlling Hg flux from these surfaces, and to estimate a net flux
      from the areas adjacent to the active mines as well as that occurring from the
      mined area pre-disturbance. Mean daily flux by substrate type ranged from 9 ng m(
      2) day(-1) to 140 ng m(-2) day(-1). Periods of net deposition of elemental Hg
      were observed when air masses originating from a mine site moved over sampling
      locations. Based on these observations and measured soil Hg concentrations we
      suggest that emissions from point and non-point sources at the mines are a source
      of Hg to the surrounding substrates with the amount deposited not being of an
      environmental concern but of interest mainly with respect to the cycling of
      atmospheric elemental Hg. Observations indicate that while some component of the
      deposited Hg is sequestered in the soil, this Hg is gradually released back to
      the atmosphere over time. Estimated pre-disturbance emissions from the current
      mine footprints based on field data were 0.1 and 1.7 kg yr(-1), compared to that
      estimated for the current non-point mining sources of 19 and 109 kg yr(-1),
      respectively.

PMID- 21741678
TI  - Investigation of different approaches to reduce allergens in asthmatic children's
      homes--the Breath of Fresh Air Project, Cornwall, United Kingdom.
AB  - During 2001 to 2004, a study was conducted to assess the indoor environmental and
      health impact of installing allergen-reducing interventions in the homes of
      asthmatic children. Based on the results of a pilot study, to determine an
      intervention that would provide improved symptom scores and a reduction in house
      dust mite allergen (Der p 1), mechanical ventilation and heat recovery (MVHR)
      systems were installed in 16 homes. Environmental and respiratory health
      assessments were conducted before and after the installation of the MVHR systems.
      The results indicated that the installation of MVHR systems reduced Der p 1
      concentrations in living room carpets and mattresses. There were significant
      reductions in symptom scores for breathlessness during exercise, wheezing, and
      coughing during the day and night. Although, there was not a parallel control
      group for the main study, the lack of change in the pilot study control group
      (who did not receive an intervention), indicated that the changes in symptom
      scores were in part to do with the intervention. Larger scale trials are needed
      to determine the efficacy of MVHR systems in homes to improve indoor air quality
      and reduce asthma symptoms.

PMID- 21741679
TI  - Mitochondrial membrane potential is a suitable candidate for assessing pollution
      toxicity in fish.
AB  - Fish inhabiting polluted estuaries are highly exposed to severe stress
      characterized by an oxidant-antioxidant imbalance. The aim of the study was to
      explore the use of stress parameters such as adenosine triphosphate/adenosine
      diphosphate (ATP/ADP) ratio, mitochondrial membrane potential (?psim) and total
      protein expression patterns as biomarkers against oxidant exposures in
      hepatocytes of Mugil cephalus living in either a contaminated (Test; Ennore) or
      uncontaminated (Control; Kovalam) estuary. Earlier, the pollutant stress impact
      was determined through light and electron microscopy studies. The ATP/ADP ratio
      was measured using high performance liquid chromatography; ?psim by fluorescent
      probe 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl benzimidazolcarbocyanine
      iodide (JC-1) dye and total protein expression patterns by protein profiling. The
      preponderance of stress impact was confirmed through microscopy studies that
      featured cytological alterations, disturbances in the surface morphology and in
      the cell organelles at the ultrastructural levels. Hepatocytes of test fish
      demonstrated a decrease in ATP and an increase in ADP and thereby alteration in
      ATP/ADP ratio (p<0.05; 20.75%). A significant disturbance (p<0.05; 26.57%) in
      ?psim with a ratio of J-aggregates/JC-1 monomer of 1 was observed for test fish
      hepatocytes compared to control group with a J-aggregates/JC-1 monomer ratio of
      1.5. Quantitative assessment of protein expression levels also revealed enhanced
      induction of both low and high molecular weight proteins in test fish
      hepatocytes. The findings highlight the use of these parameters as the highly
      sensitive biomarkers in response to contaminant exposure compared to the
      routinely used antioxidant and oxidant stress parameters in biomonitoring
      programs. Among the measured parameters, the determination of ?psim may be
      suggested as a novel candidate as a biomarker because of its greater specificity
      and rapid quantitative risk assessment of pollutant exposures.

PMID- 21741680
TI  - Mortality by neoplasia and cellular telephone base stations in the Belo Horizonte
      municipality, Minas Gerais state, Brazil.
AB  - Pollution caused by the electromagnetic fields (EMFs) of radio frequencies (RF)
      generated by the telecommunication system is one of the greatest environmental
      problems of the twentieth century. The purpose of this research was to verify the
      existence of a spatial correlation between base station (BS) clusters and cases
      of deaths by neoplasia in the Belo Horizonte municipality, Minas Gerais state,
      Brazil, from 1996 to 2006 and to measure the human exposure levels to EMF where
      there is a major concentration of cellular telephone transmitter antennas. A
      descriptive spatial analysis of the BSs and the cases of death by neoplasia
      identified in the municipality was performed through an ecological
      epidemiological approach, using georeferencing. The database employed in the
      survey was composed of three data banks: 1. death by neoplasia documented by the
      Health Municipal Department; 2. BSs documented in ANATEL ("Agencia Nacional de
      Telecomunicacoes": 'Telecommunications National Agency'); and 3. census and
      demographic city population data obtained from official archives provided by IBGE
      ("Instituto Brasileiro de Geografia e Estatistica": 'Brazilian Institute of
      Geography and Statistics'). The results show that approximately 856 BSs were
      installed through December 2006. Most (39.60%) of the BSs were located in the
      "Centro-Sul" ('Central-Southern') region of the municipality. Between 1996 and
      2006, 7191 deaths by neoplasia occurred and within an area of 500 m from the BS,
      the mortality rate was 34.76 per 10,000 inhabitants. Outside of this area, a
      decrease in the number of deaths by neoplasia occurred. The greatest accumulated
      incidence was 5.83 per 1000 in the Central-Southern region and the lowest
      incidence was 2.05 per 1000 in the Barreiro region. During the environmental
      monitoring, the largest accumulated electric field measured was 12.4 V/m and the
      smallest was 0.4 V/m. The largest density power was 40.78 MUW/cm(2), and the
      smallest was 0.04 MUW/cm(2).

PMID- 21741681
TI  - Potential use of RNA interference as therapeutic strategy in urologic cancer.

PMID- 21741682
TI  - Three cases of subcutaneous granuloma annulare of the penis: a rare presentation
      of a common disease.
AB  - OBJECTIVE: To describe three patients who presented to a single institution
      within four years of each other with isolated granuloma annulare of the penis.
      Granuloma annulare is an inflammatory disease of the dermis that can affect men
      of any age including childhood. Granuloma annulare of the penis is a remarkably
      uncommon presentation with only 12 cases previously reported. METHODS: A
      retrospective review of pathologic records was conducted confirming three cases
      of penile granuloma annulare diagnosed at our institution. RESULTS: The three
      cases are described in detail including the history, presentation, histological
      findings and treatment of each patient. The clinical variants, characteristic
      histology, classic clinical presentation, differential diagnosis and recurrence
      following surgery of granuloma annulare are reviewed. CONCLUSION: We describe
      three individuals from a single institution with isolated granuloma annulare of
      the penis suggesting this condition is more common than previously thought.
      Patients with penile granuloma annulare may present to practicing urologists and
      it is important to be familiar with this idiopathic subcutaneous disorder in
      order to avoid unnecessary aggressive surgery.

PMID- 21741683
TI  - Inflammatory myofibroblastic tumor of the bladder in a 3-year-old boy.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with unknown
      malignant potential that has been described in most organ systems. We present the
      case of a 3-year-old boy who was referred with lower urinary tract symptoms and
      macroscopic hematuria. An IMT was suspected after clinical, radiological, and
      surgical work-up, and the diagnosis was confirmed after a partial cystectomy was
      performed. A bladder-preserving approach is the treatment of choice, but close
      clinical follow-up is recommended because of the unknown biological behavior of
      these tumors.

PMID- 21741684
TI  - Scrotoschisis: an extremely rare congenital uropathy.
AB  - Scrotoschisis, the congenital extrusion of the testis through the scrotal wall,
      is very rare. We describe a new case and review the pertinent published data. A
      male neonate presented with left scrotoschisis that was repaired successfully
      with a Denis-Browne trans-scrotal orchiopexy, with antibiotic coverage. The
      testes were intrascrotal and symmetric after 2 years of follow-up. Most cases of
      scrotoschisis are unilateral and affect normal males. The immediate prognosis is
      good, but long-term results are not available. The etiology of the disease is
      unknown, but it might be related to spontaneous healed fetal intestinal
      perforations with meconium peritonitis.

PMID- 21741685
TI  - Novel immunotherapy for metastatic bladder cancer using vaccine of human
      interleukin-2 surface-modified MB 49 cells.
AB  - OBJECTIVE: To develop a novel protein-anchor technology to immobilize human
      interleukin-2 on tumor cells to induce antitumor immunity. METHODS: Interleukin-2
      surface-modified MB49 cells were prepared as a vaccine. Subcutaneous and
      pulmonary metastatic mouse models of MB49 bladder cancer were used to evaluate
      the antitumor efficiency of the vaccine. Immunohistochemistry, flow cytometric,
      and cytotoxic T-lymphocyte assay were performed to assess the proportion and
      cytotoxicity of the T lymphocytes. RESULTS: The IL-2 surface-modified MB49 cell
      vaccine inhibited tumor growth and extended the survival of the mice, and the
      vaccine-cured mice effectively resisted the second MB49 but not the RM-1 prostate
      cancer cell challenge. Furthermore, more cytotoxicity on the MB49 cells and more
      CD4-positive, CD8-positive T cells appeared in the vaccine-treated group.
      CONCLUSION: The results of our study have demonstrated that the human interleukin
      2 surface-modified MB49 bladder cancer cell vaccine induced specific antitumor
      immunity and was efficient against metastatic bladder cancer.

PMID- 21741686
TI  - Long-term functional outcomes after ileal ureter substitution: a single-center
      experience.
AB  - OBJECTIVES: To assess the indications and outcomes of ileal ureter replacement
      for ureteral reconstruction, which remains a technique of choice in certain
      cases, notably when the ureter has been injured. METHODS: A retrospective review
      of the data from patients treated with ureteroileoplasty from 1980 to 2010 was
      performed. The following data were analyzed: age, etiology of ureter injury, and
      pre- and postoperative creatinine levels. Follow-up visits occurred at 3 and 6
      months postoperatively and at least annually thereafter. RESULTS: A total of 17
      patients with a median age of 43 years were included. The main etiology of the
      ureteral defect was an iatrogenic ureteral injury after a urologic procedure
      (n=6). The mean length of hospital stay was 12.4+/-8 days (range 7-26). Four
      major complications (grade 3) and 5 minor complications (grade 2) developed. The
      median follow-up time was 174 months. The mean creatinine level before surgery,
      at 1 month after surgery, and at the last follow-up visit was 1.3+/-0.3 mg/dL
      (range 0.6-3.4), 1.4+/-0.4 mg/dL (range 0.6-3.6), and 1.8+/-0.6 mg/dL (range 0.7
      4.7), respectively. By the end of the follow-up period, 15 patients still had
      ileal ureters. Of these, 3 required dialysis. CONCLUSIONS: The indications for an
      ileal ureter have evolved in recent years. The ileal ureter appears to remain a
      reasonable option for ureteral reconstruction to preserve long-term renal
      function.

PMID- 21741687
TI  - Intrahepatic paratesticular cyst: unique presentation of vestigial remnants of
      Wolffian duct.
AB  - To report on a case of a progressively enlarging intrahepatic cyst in a 1-year
      old boy who also presented with bilateral undescended testes. At surgery, the
      lesion emerged from the anterior surface of the liver but was unexpectedly found
      to arise from the epididymis of the right testis, which was located intra
      abdominally. The histologic findings were consistent with a paratesticular cyst
      of vestigial remnants derived from the Wolffian duct. Such an unusual event has
      not been previously reported among the possible location of a paratesticular
      cyst, nor has it been described in the differential diagnosis of cystic lesions
      of the liver.

PMID- 21741688
TI  - Beyond Buck's fascia: the life and contributions of Dr. Gurdon Buck (1807-1877).

PMID- 21741689
TI  - Transverse versus vertical camera port incision in robotic radical prostatectomy:
      effect on incisional hernias and cosmesis.
AB  - OBJECTIVE: To examine the incidence of incisional hernias (IHs) and propose a
      simple modification to reduce the incidence of IHs. Robot-assisted radical
      prostatectomy (RARP) historically uses a vertical midline camera port incision to
      extract the prostate. METHODS: Of 900 consecutive RARPs, the initial 735 had a
      vertical and subsequent 165 transverse incisions. Two methods were used to
      identify IHs: clinic visits noted in the prospective database and screening using
      electronic mail. We compared the baseline factors between the vertical IH and IH
      free cohorts. The maximal scar width was recorded in 178 consecutive men
      presenting to our clinic: vertical (n=107) and transverse (n=71). RESULTS: IHs
      occurred significantly more often after a vertical incision (5.3% vs 0.6%,
      P=.005). The IH rates after a vertical incision could be estimated to be as great
      as 16.7% (18 of 108) using the electronic mail respondents or as low as 3.3% (21
      of 627) according to clinic follow-up. On univariate analysis, baseline age,
      International Index of Erectile Function 5-item questionnaire, prostate weight,
      bother score (all P<=.05), and body mass index (P=.058) were associated with an
      increased risk of an IH. After adjusting for baseline factors on multivariate
      logistic regression analysis, the relative odds of developing an IH with a
      vertical versus transverse incision was 11 (95% confidence interval 1.5-82). The
      average maximal scar width was reduced from 5.5 to 2.0 mm (P<.0001). CONCLUSION:
      In the present sample population, the vertical IH rate was estimated to be
      potentially as low as 3.3% or as great as 16.7%. On multivariate analysis, a
      greater body mass index and larger prostate size significantly increased the risk
      of hernia development. Transverse incisions dramatically reduced the rate of IHs
      and the maximal scar width. The IH rates varied significantly by reporting
      method.

PMID- 21741690
TI  - Enzymatic dissolution of calcium and struvite crystals: in vitro evaluation of
      biochemical requirements.
AB  - OBJECTIVE: To evaluate the factors that affect the enzymatic dissolution rate of
      calcium oxalate monohydrate (COM), calcium phosphate (brushite), and magnesium
      ammonium phosphate (struvite) crystals as enzymatic digestion of kidney stones
      could enhance lithotripsy or provide alternatives to surgical removal. METHODS:
      At pH 4.2, pelleted COM crystals were combined with oxalate decarboxylase (ODC
      from Bacillus subtilis), oxalate oxidase (from Hordeum vulgare), or control.
      Crystal dissolution was followed by measuring increases in solution calcium ion
      concentration. For phosphate-based crystals, the rates of phosphorolysis by the
      enzyme purine nucleoside phosphorylase (PNP, assay form) were compared to the
      control solution using spectrophotometry. RESULTS: The addition of ODC to COM
      crystals resulted in production of highly soluble calcium formate and a 15-fold
      increase in COM solubility. By adding a formate-catabolizing enzyme (formate
      dehydrogenase), dissolution increased 47-fold compared with controls with nearly
      one half of the mineral dissolved. Oxalate oxidase showed much lower activity
      than ODC in COM dissolution. Using inorganic phosphate as a substrate, PNP was
      able to dissolve both brushite and struvite minerals in water at concentrations
      near saturation. Measuring dissolution by adding more PNP was not possible
      because of equilibrium and assay detection restraints. CONCLUSION: Stone
      dissolution using enzymes appears to be viable, particularly for oxalate-based
      minerals. In a closed system, product inhibition by calcium formate appeared to
      limit the extent of COM crystal dissolution using ODC. Although phosphate
      containing minerals appear to be suitable phosphate sources for PNP, the
      reversibility of the reaction limits the use of this enzyme.

PMID- 21741691
TI  - Urethral ultrasound as a screening tool for stricture recurrence after oral
      mucosa graft urethroplasty.
AB  - OBJECTIVE: To evaluate the efficacy of sonourethrography (SUG) in combination
      with voiding pattern analysis to determine success after oral mucosa graft (OMG)
      urethroplasty. OMG urethroplasty is a standard treatment for men with recurrent
      urethral stricture. Because of its performance, the optimum follow-up algorithm
      remains controversial. MATERIAL AND METHODS: Forty-nine patients (mean age 51
      years) who underwent OMG urethroplasty were retrospectively identified. All men
      were subjected to a validated voiding questionnaire (International Prostate
      Symptom Score [IPSS]), SUG, uroflowmetry, and residual urine measurement. The
      predictive value was analyzed with regard to stricture recurrence or patency as
      well as to urethral diameter. Retrograde urethrography was done to confirm the
      diagnosis. RESULTS: Strictures were bulbar in 39, penile in 4, and combined in 6
      patients. Mean stricture length was 3.8 cm (range 1-10). Mean follow-up after
      surgery was 35 (range 15-70) months. SUG showed a mean diameter of 7.6 mm for
      bulbar grafts and 4.6 mm for penile grafts. Stricture recurrence was seen in 4
      (8%) patients, yielding a significantly lower urethral width of 2.3 mm (P<.005).
      Retrograde urethrography confirmed the patency status in all. The average maximum
      flow rate after successful repair was 36.6 mL/s, whereas those with recurrent
      strictures showed rates of 11.2 (P<.03). Similar results were achieved for
      residual urine (P<.05). IPSS values increased from 5.1 to 12.5 in patients with
      recurrence (P<.01). CONCLUSION: An algorithm consisting of SUG, uroflowmetry,
      residual urine and IPSS assessment reliably identifies stricture recurrence.
      Routine retrograde urethrography may therefore be unnecessary in the follow-up of
      OMG urethroplasty.

PMID- 21741693
TI  - Laparoendoscopic single-site repair of incisional hernias after urological
      surgery.
AB  - OBJECTIVE: To report the first series of postoperative ventral hernias (POVH)
      repair with laparoendoscopic single-site (LESS) approach after urological
      procedures. POVH are well-known complications of urological surgery and often
      require surgical correction. Minimally invasive repair techniques have been
      developed to diminish parietal trauma and enhance functional results. METHODS:
      This study was based on a retrospective review of patients undergoing POVH repair
      after urological surgery at an academic institution from 2004 to 2010. Patient
      characteristics, perioperative details, as well as follow-up were reviewed and
      summarized. Using a transperitoneal approach, abdominal wall defect was
      identified, prepared, and closed with a mesh tailored to cover 3-5 cm beyond the
      edge of the defect and secured in a double-crown fashion. RESULTS: In 3 patients
      POVH was represented by a port-site hernia after laparoscopic partial
      nephrectomy; in the remaining 2 patients POVH occurred at midline following
      radical cystectomy. Hernia occurrence was identified within 2 months from the
      initial surgery in all but 1 patient. Blood loss was minimal, operative times
      were 30-150 minutes, and no intraoperative complications occurred. Three patients
      developed a transient seroma and 1 patient had ileus. Over a 1- to 20-month
      follow-up, there have been no wound or mesh complications, and no hernia
      recurrences were identified. CONCLUSION: In this initial series, POVH after
      urological surgery were successfully treated with LESS approach. In experienced
      hands, LESS may provide a viable alternative to conventional laparoscopy for POVH
      repair. More studies are needed to confirm these initial results and to determine
      whether reduced parietal trauma favors LESS in POVH repair.

PMID- 21741692
TI  - Performance of the American Urological Association Symptom Index with and without
      an additional urge incontinence item.
AB  - OBJECTIVE: To examine the value of adding an urge incontinence question to the
      American Urological Association Symptom Index (AUASI) among men in the
      Complementary and Alternative Medicine for Urological Symptoms (CAMUS) trial.
      METHODS: The CAMUS study was a randomized trial of Saw palmetto fruit extract
      versus placebo among men aged >=45 years with an AUASI score of >=8 and <=24. The
      baseline measurements included the AUASI, a question about urge incontinence
      (UI), the International Prostate Symptom Score quality of life question, and the
      Benign Prostatic Hyperplasia Impact Index. We correlated the items and scales and
      examined whether adding the UI question resulted in better prediction of disease
      specific health status. RESULTS: The mean age of the 369 men in the CAMUS trial
      was 61 years, and mean baseline AUASI score was 14.6. UI was reported
      infrequently; about 82% of the respondents answered the question "not at all" or
      "<1 time in 5." UI correlated significantly with all other AUASI items, except
      for weak stream; the strongest correlation was to urgency (R=0.51, P<.0001). The
      correlation between the AUASI score and the AUASI+UI score was 0.98 (P<.0001). In
      a logistic regression analysis predicting the International Prostate Symptom
      Score quality of life score, adding UI to the AUASI slightly increased the
      discriminating ability (c statistic increased from 0.77 to 0.78, P<.0001).
      Similarly, in a linear regression analysis predicting the Benign Prostatic
      Hyperplasia Impact Index score, adding UI to the AUASI slightly increased the
      predictive ability (R2 statistic increased from 0.22 to 0.26, P<.0001).
      CONCLUSION: According to our analysis in the CAMUS trial population, the value of
      adding a UI question to the AUASI in terms of predicting bother seemed small at
      best.

PMID- 21741694
TI  - Clinical effects of irinotecan hydrochloride in combination with cisplatin as
      neoadjuvant chemotherapy in locally advanced cervical cancer.
AB  - OBJECTIVE: To evaluate the toxicity and efficacy of irinotecan plus cisplatin
      neoadjuvant chemotherapy (NACT) for cervical cancer. METHODS: A total of 120
      cases with cervical cancer were divided into 2 groups and retrospectively
      reviewed: Sixty FIGO IB2-IIB patients in NACT group were treated with 2 cycles of
      irinotecan 60 mg/m(2) on days 1 and 8 plus cisplatin 60 mg/m(2) on day 1 followed
      by surgery. Sixty FIGO IB2-IIB patients in control group were treated directly
      with surgery. RESULTS: The 60 patients in NACT group received a total of 120
      cycles. Grades III and IV neutropenia and diarrhea were seen in 15.8% and 11.7%,
      respectively, of all chemotherapy cycles. Six (10.0%) patients achieved complete
      remission, 33 (55.0%) achieved partial remission, 21 (35.0%) remained stable, and
      none had disease progression. Postoperatively the deep cervical stromal invasion
      and positivity of surgical margins were significantly fewer in the NACT group.
      The pelvic lymph node metastasis rate of responders to NACT was significantly
      lower than that of non-responders (12.8% vs 38.1%). With a median follow-up of 29
      and 30 months, the intra-pelvic recurrence rate of the NACT group was
      significantly lower than that of the control group (3/60 vs 11/60, p=0.023), the
      2-year recurrence-free survival and the 2-year overall survival was 82.3% and
      86.1% in the NACT group, and 86.3%, 87.9% in the control group with no
      significant difference. Multivariate analysis showed that response to NACT was
      the only factor associated with survival (p=0.036). CONCLUSION: Irinotecan plus
      cisplatin NACT for cervical cancer has high efficacy and tolerable toxicity, and
      can significantly reduce the rates of deep cervical stromal invasion and positive
      surgical margins. Pelvic lymph node metastasis decreases significantly in
      responders compared with non-responders. The response to NACT can be considered
      as an independent prognostic factor.

PMID- 21741695
TI  - Treatment of chemotherapy resistant ovarian cancer with a MDR1 targeted oncolytic
      adenovirus.
AB  - OBJECTIVE: Multidrug resistance gene 1 (MDR1) mediated resistance to
      chemotherapeutic agents is a major obstacle for the therapy of various cancer
      types. The use of conditionally replicating adenoviruses (CRAds) is dependent on
      molecular differences between tumor cells and non tumor cells. Transcriptional
      targeting of CRAd replication is an effective way to control replication
      regulation. The aim of this study was to evaluate the effect of a MDR1 targeted
      fiber-modified CRAd against chemotherapy resistant ovarian cancer. METHODS: MDR1
      expression was evaluated in chemotherapy naive and pretreated ovarian cancer
      cells and various control cells. We constructed 2 variants of a fiber-modified
      CRAd, Ad5/3MDR1E1 and Ad5/3MDR1E1?24 containing the MDR1 promoter to control
      viral replication via the E1A gene. The MDR promoter activity and cell killing
      efficacy were evaluated in vitro. Orthotopic murine models of peritoneally
      disseminated ovarian cancer were utilized to evaluate the preclinical efficacy of
      MDR targeted CRAds in vivo. To evaluate the liver toxicity of MDR1 targeted
      CRAds, we compared Ad5/3MDR1E1 with Ad5/3?24, a CRAd that replicates in cancer
      cells inactive in the Rb/p16 pathway by use of an in vivo hepatotoxicity model.
      RESULTS: We demonstrate efficient oncolysis of Ad5/3MDR1E1 in both chemotherapy
      resistant ovarian cancer cell lines and in primary tumor cells from pretreated
      patients as well as therapeutic efficacy in an orthotopic mouse model.
      Ad5/3MDR1E1 demonstrated significantly decreased liver toxicity compared to other
      5/3-fiber modified control vectors examined. CONCLUSIONS: In summary, Ad5/3MDR1E1
      is an efficient and safe gene therapy approach for specific targeting of
      chemotherapy resistant cancer cells.

PMID- 21741696
TI  - The impact of surgical guidelines and periodic quality assessment on the staging
      of endometrial cancer.
AB  - OBJECTIVE: To determine the impact of surgical guidelines and transparent
      periodic assessment of surgical quality on endometrial cancer (EC) staging by
      gynecologic oncologists in a single institution and to identify process-of-care,
      patient-specific, and disease-specific risk factors that influence surgical
      quality. METHODS: In January 2004, a prospective treatment algorithm was
      implemented for EC at our institution. The number of nodes harvested was a
      surrogate, and staging quality from 2004 to 2008 (quality assessment [QA]
      interval) was compared with the previous 5 years (pre-QA interval). Since 2004,
      low-risk cases based on frozen section examination had not undergone
      lymphadenectomy and were excluded. Independent patient-specific, disease
      specific, and surgery-related risk factors influencing lymphadenectomy quality
      during both intervals were identified with multivariable logistic regression
      analysis. RESULTS: Pelvic and para-aortic lymph node dissection (LND) in surgical
      EC management before QA (n=420) were 77.9% and 48.8% vs 89.3% and 83.4% during
      the QA (n=561) (P<.001). The median number of pelvic and para-aortic nodes
      harvested in LND was 29 and 10 before QA vs 34 and 16 during the QA interval
      (P<.001). With acceptance of stringent criteria for defining systematic LND (mean
      node count-1 SD) during the QA, systematic pelvic (>=22 nodes) and para-aortic
      (>=10 nodes) LNDs occurred in 57.4% and 25.7% of cases before QA vs 77.9% and
      70.7% during the QA interval (P<.001). In patients with LND, rates of systematic
      pelvic and para-aortic LND were 73.7% and 53.0% before vs 87.2% and 84.8% after
      QA (P<.001). Multivariable logistic regression analysis showed independent
      factors influencing systematic pelvic and para-aortic LND (P<.01): surgeon and
      stage during the pre-QA interval vs surgical approach; intraoperative ascites;
      body mass index; surgeon; patient age; and myometrial invasion after QA
      implementation. CONCLUSION: Inclusion of detailed surgical guidelines and
      transparent periodic assessment of surgical quality translated to dramatic
      improvement in quality of surgical EC staging. This implementation was associated
      with a transition to more patient-specific risk factors influencing systematic
      LND. Although surgical quality metrics were markedly enhanced during QA,
      persistent variability observed among surgeons and the change in surgical
      approach render continuous QA and improvement obligatory.

PMID- 21741697
TI  - Altered gene transcription and telomere length in trout embryo and larvae
      obtained with DNA cryodamaged sperm.
AB  - Sperm cryopreservation could entail DNA damage, promoting base oxidization and
      strand breaks. In a previous work we showed that trout DNA damaged sperm is able
      to fertilize leading to embryo loss when the repair system of the oocyte is
      inhibited. Here we have analysed the later effects on embryo and larvae of
      fertilizing trout oocytes with cryopreserved DNA-damaged spermatozoa. Fish have
      weak sperm selection mechanisms, are very prolific and have external embryo
      development, being convenient models for this type of study. We cryopreserved
      rainbow trout semen using extenders containing egg yolk or their low density
      lipoprotein fraction to obtain samples with different degrees of DNA damage. DNA
      fragmentation was evaluated using the Comet assay and telomere length using
      quantitative-PCR. Fertilization trials were performed and the transcription at
      different developmental stages of telomerase reverse transcriptase (Tert) and
      eight genes related with embryo growth and development (Igf1, Igf2, Igfr1a,
      Igfr1b, Gh1, Gh2, Ins1 and Ins2) were analyzed using quantitative-PCR in
      surviving embryos and larvae. Results showed an increase in sperm DNA
      fragmentation after both cryopreservation procedures as well as a decrease in
      sperm telomere length. Larvae obtained with damaged sperm showed longer telomeres
      and Tert overexpression. The transcription of the analyzed genes in these embryos
      and larvae was also modified with respect to the control, most of them as an
      increase at hatch. We conclude that fertilization with cryopreserved DNA-damaged
      spermatozoa significantly affects offspring performance, detectable as an
      increase in telomere length as well as some alterations in gene expression in
      surviving embryo and larvae.

PMID- 21741698
TI  - Managing post-prostatectomy stress urinary incontinence.

PMID- 21741699
TI  - Global anti-smoking campaigns urgently needed.

PMID- 21741700
TI  - Urinary incontinence in men after formal one-to-one pelvic-floor muscle training
      following radical prostatectomy or transurethral resection of the prostate
      (MAPS): two parallel randomised controlled trials.
AB  - BACKGROUND: Urinary incontinence is common immediately after prostate surgery.
      Men are often advised to do pelvic-floor exercises, but evidence to support this
      is inconclusive. Our aim was to establish if formal one-to-one pelvic floor
      muscle training reduces incontinence. METHODS: We undertook two randomised trials
      in men in the UK who were incontinent 6 weeks after radical prostatectomy (trial
      1) or transurethral resection of the prostate (TURP; trial 2) to compare four
      sessions with a therapist over 3 months with standard care and lifestyle advice
      only. Randomisation was by remote computer allocation. Our primary endpoints,
      collected via postal questionnaires, were participants' reports of urinary
      incontinence and incremental cost per quality-adjusted life year (QALY) after 12
      months. Group assignment was masked from outcome assessors, but this masking was
      not possible for participants or caregivers. We used intention-to-treat analyses
      to compare the primary outcome at 12 months. This study is registered, number
      ISRCTN87696430. FINDINGS: In the intervention group in trial 1, the rate of
      urinary incontinence at 12 months (148 [76%] of 196) was not significantly
      different from the control group (151 [77%] of 195; absolute risk difference [RD]
      -1.9%, 95% CI -10 to 6). In trial 2, the difference in the rate of urinary
      incontinence at 12 months (126 [65%] of 194) from the control group was not
      significant (125 [62%] of 203; RD 3.4%, 95% CI -6 to 13). Adjusting for
      minimisation factors or doing treatment-received analyses did not change these
      results in either trial. No adverse effects were reported. In both trials, the
      intervention resulted in higher mean costs per patient (L180 and L209
      respectively) but we did not identify evidence of an economically important
      difference in QALYs (0.002 [95% CI -0.027 to 0.023] and -0.00003 [-0.026 to
      0.026]). INTERPRETATION: In settings where information about pelvic-floor
      exercise is widely available, one-to-one conservative physical therapy for men
      who are incontinent after prostate surgery is unlikely to be effective or cost
      effective. The high rates of persisting incontinence after 12 months suggest a
      substantial unrecognised and unmet need for management in these men. FUNDING:
      National Institute of Health Research, Health Technology Assessment (NIHR HTA)
      Programme.

PMID- 21741701
TI  - A strategy to establish a gene-activated matrix on titanium using gene vectors
      protected in a polylactide coating.
AB  - Bioactive implants are promising tools in regenerative medicine. Here we describe
      a versatile procedure for preparing a gene-activated matrix on titanium.
      Lyophilized copolymer-protected gene vectors (COPROGs) suspended in poly(d,l
      lactide) (PDLLA) solutions in ethyl acetate were used to varnish solid surfaces.
      The gene-activated PDLLA surfaces were first established on polypropylene 96-well
      plates. Vector release from these surfaces in aqueous buffer, cell viability and
      gene transfer efficiency to NIH 3T3 fibroblasts was strongly dependent on the
      vector dose and its ratio to PDLLA film thickness. A detailed analysis of these
      relationships allowed establishing correlations which can be used to calculate
      suitable combinations of COPROGs and PDLLA yielding optimal gene transfer
      efficiency. This was verified with COPROG-activated PDLLA coatings on titanium
      foils. HEK 293 and mesenchymal stem cells expressed the BMP-2 gene comprised in
      the gene-activated surface in a manner that was consistent with the predicted
      dose-response and toxicity profiles found in NIH 3T3 cells. The systematic
      procedure presented here for identifying optimal coating compositions can be
      applied to any combination of vector type and coating material.

PMID- 21741702
TI  - Galactosylated cellulosic sponge for multi-well drug safety testing.
AB  - Hepatocyte spheroids can maintain mature differentiated functions, but collide to
      form bulkier structures when in extended culture. When the spheroid diameter
      exceeds 200 MUm, cells in the inner core experience hypoxia and limited access to
      nutrients and drugs. Here we report the development of a thin galactosylated
      cellulosic sponge to culture hepatocytes in multi-well plates as 3D spheroids,
      and constrain them within a macroporous scaffold network to maintain spheroid
      size and prevent detachment. The hydrogel-based soft sponge conjugated with
      galactose provided suitable mechanical and chemical cues to support rapid
      formation of hepatocyte spheroids with a mature hepatocyte phenotype. The
      spheroids tethered in the sponge showed excellent maintenance of 3D cell
      morphology, cell-cell interaction, polarity, metabolic and transporter function
      and/or expression. For example, cytochrome P450 (CYP1A2, CYP2B2 and CYP3A2)
      activities were significantly elevated in spheroids exposed to beta
      naphthoflavone, phenobarbital, or pregnenolone-16alpha-carbonitrile,
      respectively. The sponge also exhibits minimal drug absorption compared to other
      commercially available scaffolds. As the cell seeding and culture protocols are
      similar to various high-throughput 2D cell-based assays, this platform is readily
      scalable and provides an alternative to current hepatocyte platforms used in drug
      safety testing applications.

PMID- 21741703
TI  - The biomechanical behavior and host response to porcine-derived small intestine
      submucosa, pericardium and dermal matrix acellular grafts in a rat abdominal
      defect model.
AB  - Several porcine-derived acellular biologic grafts are increasingly used in
      abdominal wall reconstruction due to the limitations of synthetic meshes in many
      clinical situations. However, relatively little is known so far about their
      comparative mechanical characteristics and performance after defect repair. We
      therefore investigated three most commonly used porcine-derived acellular
      biomaterials, small intestine submucosa (P-SIS), pericardium (P-PC) and acellular
      dermal matrix (P-ADM) immediately after prepared, and their effectiveness,
      biomechanical and histological characteristics in repairing full-thickness
      abdominal defect in a rat model. P-PC had the best native performance in the
      burst strength, tensile strength and ball burst among the three porcine-derived
      scaffolds. P-SIS showed a significantly higher water vapor transmission in
      comparison with P-PC or P-ADM. Abdominal wall defects in rats were all satisfied
      repaired with P-SIS, P-PC or P-ADM. No laxity or fistula was observed in the
      repaired abdominal wall in the P-SIS group up to 8 weeks after surgery. However,
      there was a tendency for high postoperative abdominal eventration in the P-ADM
      and P-PC groups as compared with the P-SIS group. With regard to overall aspects
      of the postoperative laxity, intra-abdominal adhesion formation, tensile stress,
      stretchability, and degree of tissue ingrowth in terms of collagen deposition and
      neovascularization, P-SIS exhibits clear advantages over P-PC as well as P-ADM
      after large abdominal wall defect reconstruction.

PMID- 21741704
TI  - The role of fibrin E on the modulation of endothelial progenitors adhesion,
      differentiation and angiogenic growth factor production and the promotion of
      wound healing.
AB  - Severe skin loss constitutes a major unsolved clinical problem worldwide. For
      this reason, in the last decades there has been a major push towards the
      development of novel therapeutic approaches to enhance skin wound healing. Neo
      vessel formation through angiogenesis is a critical step during the wound healing
      process. Besides the contribution of pre-existing endothelial cells (EC),
      endothelial progenitor cells (EPCs) have also been implicated in wound healing
      acting either by differentiating into EC that incorporate the neo-vessels, or via
      the production of paracrine factors that improve angiogenesis. Here we tested the
      importance of different extracellular matrices (ECM) in regulating the angiogenic
      and wound healing potential of cord blood-derived EPC (CB-EPC). We compared the
      properties of several ECM and particularly of fibrin fragment E (FbnE) in
      regulating EPC adhesion, proliferation, differentiation and healing-promotion in
      vitro and in vivo. Our results show that CB-EPCs have increased adhesion and
      endothelial differentiation when plated on FbnE compared to collagens,
      fibronectin or fibrin. Using integrin neutralizing antibodies, we show that CB
      EPC adhesion to FbnE is mediated by integrin alpha5beta1. Gene expression
      analysis of CB-EPCs plated on different substrates revealed that CB-EPC grown on
      FbnE shows increased expression of paracrine factors such as VEGF-A, TGF-beta1,
      SDF-1, IL-8 and MIP-1alpha. Accordingly, conditioned media from CB-EPC grown on
      FbnE induced EC tube formation and monocyte migration in vitro. To test the wound
      healing effects of FbnE in vivo we used an FbnE enriched scaffold in a cutaneous
      wound healing mouse model. In accordance with our in vitro data, co
      administration of the FbnE enriched scaffold with CB-EPC significantly
      accelerated wound closure and wound vascularization, compared FbnE enriched
      scaffold alone or to using collagen-based scaffolds. Our results show that FbnE
      modulates several CB-EPC properties in vivo and in vitro, and as such promotes
      wound healing. We suggest the use of FbnE-based scaffolds represents a promising
      approach to resolve wound healing complications arising from different
      pathologies.

PMID- 21741705
TI  - Store-operated calcium entry and non-capacitative calcium entry have distinct
      roles in thrombin-induced calcium signalling in human platelets.
AB  - Phosphatidylserine (PS)-exposing platelets accelerate coagulation at sites of
      vascular injury. PS exposure requires sustained Ca2+ signalling. Two distinct
      Ca2+ entry pathways amplify and sustain platelet Ca2+ signalling, but their
      relative importance in human platelets is not known. Here we examined the
      relative roles of store-operated Ca2+ entry (SOCE) and non-capacitative Ca2+
      entry (NCCE) in thrombin-induced Ca2+ signalling and PS exposure by using two
      Ca2+ channel blockers. BTP-2 showed marked selectivity for SOCE over NCCE. LOE
      908 specifically blocked NCCE under our conditions. Using these agents we found
      that SOCE is important at low thrombin concentrations whereas NCCE became
      increasingly important as thrombin concentration was increased. PS exposure was
      reduced by LOE-908, and only activated at thrombin concentrations that also
      activate NCCE. In contrast, BTP-2 had no effect on PS exposure. We suggest that
      SOCE amplifies and sustains Ca2+ signalling in response to low concentrations of
      thrombin whereas both NCCE and SOCE are important contributors to Ca2+ signalling
      at higher thrombin concentrations. However, despite being involved in Ca2+
      signalling at high thrombin concentrations, SOCE is not important for thrombin
      induced PS exposure in human platelets. This suggests that the route of Ca2+
      entry is an important regulator of thrombin-induced PS exposure in platelets.

PMID- 21741706
TI  - Correlation of CYP2B6, CYP2C19, ABCC4 and SOD2 genotype with outcomes in
      allogeneic blood and marrow transplant patients.
AB  - CYP2B6, CYP2C19, ABCC4, and SOD2 have been implicated in adverse drug reactions
      and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who
      received high dose CPA treatment were genotyped for variants in these genes and
      the results were correlated with toxicity and relapse. CYP2B6 genotype
      significantly influenced overall toxicity suggesting active CYP2B6 alleles led to
      higher rates of overall toxicity. The p.R487C deficiency allele was significantly
      associated with a lower rate of overall toxicity and a higher rate of relapse.
      SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related
      overall toxicity and significantly lower relapse rates by Kaplan-Meier analysis
      although the SOD2 finding regarding relapse was not significant when evaluated by
      the cumulative incidence function.

PMID- 21741707
TI  - Plumbagin treatment leads to apoptosis in human K562 leukemia cells through
      increased ROS and elevated TRAIL receptor expression.
AB  - This study examined the ability of plumbagin to induce apoptosis in chronic
      myelogenous leukemia (CML). Plumbagin exposure led to a significant reduction in
      cell viability and the induction of apoptosis. Mechanistically, plumbagin
      treatment led to elevated levels of ROS. Plumbagin-induced apoptosis was
      inhibited by N-acetyl L-cysteine (NAC) and PEG-catalase. Furthermore, plumbagin
      exposure led to elevated expression of DR4 and DR5 and increased killing through
      soluble TRAIL. The plumbagin-induced increase in DR4 and DR5 was inhibited by
      treatment with NAC. Together, this study suggests that plumbagin may be an
      effective treatment of CML through increased sensitivity to TRAIL-mediated
      killing.

PMID- 21741708
TI  - The redox state of Ipomoea nil 'Scarlet O'Hara' growing under ozone in a
      subtropical area.
AB  - The occurrence of visible leaf injury caused by ozone in Ipomoea nil 'Scarlet
      O'Hara' may be regulated by their redox state, affecting its bioindicator
      efficiency. Thus, this study aimed to determine whether the redox state of I. nil
      plants in a subtropical area (Sao Paulo, SE-Brazil) contaminated by ozone
      oscillates, and to identify the environmental factors behind these variations. We
      comparatively evaluated indicators of redox state (ascorbic acid, glutathione,
      superoxide dismutase, ascorbate peroxidase, glutathione reductase) and leaf
      injury during nine field experiments of 28 days each. The variations in the redox
      indicators were explained by the combined effects of chronic levels of ozone and
      meteorological variables (mainly global solar radiation and air temperature) 3-6
      days prior to the sampling days. The ascorbic acid and glutathione were crucial
      for increasing plant tolerance to ozone. Weak visible injury was observed in all
      experiments and occurred in leaves with low levels of ascorbic and
      dehydroascorbic acids.

PMID- 21741709
TI  - Current strategies for eradication of paratuberculosis and issues in public
      health.
AB  - Paratuberculosis is a regional chronic enteritis caused by Mycobacterium avium
      subsp. paratuberculosis (MAP). The first complete description of this disease was
      made in 1895, but previous reports on clinical cases compatible with this entity
      can already be found in the literature of early 1800 s. Its obvious similarities
      with tuberculosis gave it the name of paratuberculosis, although it was clearly
      recognized it was not the same entity as that caused by mammal tuberculosis
      mycobacteria. Eradication has been considered the ideal goal for control of
      paratuberculosis, but the lack of efficient diagnostic tools and the high costs
      involved in testing and culling approaches have shifted the focus to control
      given the better benefit/cost ratios of more conservative strategies like
      vaccination. Up to now the control of paratuberculosis has been driven by its
      negative effects on the ruminant farming industry, however recent growing
      discussion on its links with human regional enteritis might require control
      strategies changes if a zoonotic role is considered by Public Health authorities.
      Paratuberculosis was described nearly 40 years earlier than what is usually
      considered the first full type description of human regional chronic enteritis or
      inflammatory bowel disease (IBD) which is pathologically a similar entity. No
      microbiological evidence was found to link both entities until the 1980s in spite
      of a number of more or less serious attempts. Afterwards there have been numerous
      studies showing the association of MAP with human IBD. Microbiological,
      pathological, immunological, therapeutic and epidemiologic associations have not
      been considered proof of causality and, currently, no widely accepted consensus
      has been reached about the etiologic role of MAP in human cases. This puts
      ruminant farming under suspicion and causes a difficult balance between Public
      Health precaution and practical control measures.

PMID- 21741710
TI  - John W. Prineas awarded the Order of Australia.

PMID- 21741711
TI  - Complications and clinical analysis of 416 consecutive cochlear implantations.
AB  - OBJECTIVES: Cochlear implantation is a safe technique with a relatively low
      complication rate. However, certain complications may require specific attention
      to treat. The purpose of this study was to investigate complications of cochlear
      implantation for prevention and therapy. STUDY DESIGN: Retrospective case series
      at a tertiary referral center in China. METHODS: The patients (n=416) who
      received cochlear implants in our department between 2000 and 2010 were followed
      up (range, 3 months to 10 years). The complications were identified as "minor" or
      "major". All complications were systematically reviewed, and their causes were
      analyzed for prevention and therapy. RESULTS: There were a total of 29
      complications (7%). The minor were 23 cases (5.5%), including postoperative
      subcutaneous hematoma in 13 cases, acute otitis media in 2 cases, postoperative
      wound infection in 2 cases, delayed facial paralysis in 1 case, clonic facial
      spasm in 1 case, and severe vertigo in 4 cases. The major were 6 cases (1.5%),
      including cerebrospinal fluid leakage in 2 cases, implant-related infection and
      extrusion in 1 case, tympanic membrane perforation induced electrode exposed in 1
      case, implantation failure due to cochlear ossification in 1 case, and magnet
      displacement in 1 case. CONCLUSIONS: Although cochlear implantation is popular,
      it is essential to decrease the incidence of complications.

PMID- 21741712
TI  - Male breast uptake of 99m-Tc sestamibi in myocardial perfusion imaging.

PMID- 21741714
TI  - Agreement between adjusted indirect comparison and simplified network meta
      analyses on prasugrel and ticagrelor (Reply to Passaro et al. - Int J Cardiol
      2011).

PMID- 21741713
TI  - Drug-eluting stents for off-label indications in real clinical world: evidence
      based or 'intuition' based clinical practice?
AB  - BACKGROUND: The use of drug-eluting stents (DES) is an example of the disparity
      between recommendations given by regulatory agencies and the real clinical world.
      Such disparity might lead cardiologists to adopt different routines in the use of
      DES. We aimed to assess variability of off-label DES use between hospitals and to
      what extent it can be explained by differences in patient or hospital
      characteristics. METHODS: Characteristics of consecutive patients receiving DES
      in 29 hospitals were recorded. Individual and hospital determinants of receiving
      DES for off-label indications were assessed by multilevel logistic regression.
      RESULTS: 1903 patients were recruited and 1188 (62.4%) received DES for off-label
      indications. Individual variables associated with off-label use were age (OR 1.01
      (1-1.02)), previous percutaneous (OR 2.24 (1.68-2.97)) or surgical (2.41 (1.52
      3.84)) revascularization, repeated procedure at the same admission (OR 4.66 (2.7
      8.05)), receiving two (OR 4.17 (3.24-5.37)) or three or more DES (OR 14.12 (9.08
      21.96)) vs one. Adjusting for individual variables, the Odds of receiving DES for
      off-label indication was higher in public funding hospitals with surgery
      availability vs private hospitals: 1.49 (0.86-2.6), and in public hospitals
      without surgery vs public with surgery availability: OR 1.76 (1.02-3.03).
      Interhospital variability reminded significant after adjustment for individual
      and contextual variables. CONCLUSION: Off-label DES use is highly variable
      between centers. Although this variability is partially determined by hospital
      type of funding and cardiac surgery availability, the substantial interhospital
      variability after multilevel adjustment suggests heterogeneity in the process of
      care.

PMID- 21741715
TI  - Farm level risk factors associated with severity of post-weaning multi-systemic
      wasting syndrome.
AB  - A cross-sectional study involving 147 pig farms across England was conducted in
      2008-2009. Farm severity of post-weaning multi-systemic wasting syndrome (PMWS)
      was estimated through the use of an algorithm that combined data on post-weaning
      mortality, PMWS morbidity and proportion of porcine circovirus type 2 PCR
      positive pigs. Farms were classified as non/slightly, moderately or highly
      affected by PMWS. Data on potential PMWS risk factors were collected through
      interviews, on-farm assessment and serological sampling. Risk factors were
      identified using multivariable ordinal logistic regression and multivariable
      linear regression. Factors associated with increased PMWS severity were rearing
      growers indoors (OR=23.7), requiring a higher number of veterinarian visits per
      year (OR=9.6), having poorly isolated hospital pens (OR=6.4), buying replacement
      boars (OR=4.8) and seropositivity to Mycoplasma hyopneumoniae (OR=4.29); factors
      associated with decreased PMWS severity were low stocking density for growers
      (OR=0.07), adjusting diets at least three times between weaning and 14 weeks of
      age (OR=0.12), and requiring visitors to be at least 2 days pig free (OR=0.14).
      This study provides evidence of the association between environmental and
      management factors and PMWS severity, and suggests that other pathogens may be
      important co-factors for the disease. In addition, this study highlights the
      potential efficacy of biosecurity measures in the reduction/prevention of within
      farm PMWS severity.

PMID- 21741716
TI  - Preoperative treatment with capecitabine, bevacizumab and radiotherapy for
      primary locally advanced rectal cancer--a two stage phase II clinical trial.
AB  - BACKGROUND AND PURPOSE: The aim of this single-arm multicenter phase II clinical
      trial was to assess the feasibility and tolerability of preoperative radiotherapy
      and simultaneous capecitabine and bevacizumab. Secondary endpoints were
      downstaging-rate and induction of complete pathological response. MATERIAL AND
      METHODS: Patients with cT3 rectal cancer were eligible. Capecitabine (825 mg/sqm
      twice daily on radiotherapy-days weeks 1-4) and bevacizumab (5 mg/kg on days 1,
      15 and 29) were administered concurrently to pelvic radiotherapy (1.8 Gy daily up
      to 45 Gy in 5 weeks). Surgery followed 6-8 weeks later. A two-stage trial was
      designed with early termination at eight patients if more than three patients had
      experienced a common toxicity criteria >=grade 3 according to the NCI CTC
      guidelines. RESULTS: In the first stage eight patients were enrolled. Median age
      was 70 years (range 55-76) and ECOG PS 0/1 (%) was 87.5/12.5. Major side effects
      were mostly intestinal bleeding (grade 3, 25%), diarrhea (grade 3, 25%), perianal
      and abdominal pain (grades 3 and 4, 25%) followed by anemia (grade 3, 12.5%).
      Tumor downstaging was observed in 37.5% of patients with complete pathological
      response in two patients (25%). CONCLUSIONS: After interim analysis of
      feasibility and tolerability, accrual was terminated according to protocol due to
      >=grade 3 toxicities in 50% of patients. Complete pathological response was seen
      in 25% of patients but was accompanied by considerable toxicity. Further clinical
      trials are needed to clarify the role of bevacizumab in this setting.

PMID- 21741717
TI  - Is contrast enhancement required to visualize a known breast tumor in a pre
      operative CT scan?
AB  - BACKGROUND AND PURPOSE: A pre-operative CT scan with contrast enhancement (CE)
      has recently been proposed to improve tumorbed delineation in breast conserving
      therapy. However, it is not clear whether CE is required for visualization of a
      known breast tumor. The main aims of this study were to compare the sensitivity
      of a CE-CT scan with a native CT scan (i.e. without CE) and to identify
      characteristics predictive for the requirement of CE. PATIENTS AND METHODS: Both
      a CE-CT and a native CT were made in 58 breast cancer patients (age 37-75 yr),
      prior to breast conserving surgery. Visibility of the tumor on CT was scored by
      three observers (clearly visible/doubtful/not visible). Age, tumor size, palpable
      tumor yes/no, histology, and visibility on mammography were analyzed with respect
      to the visibility of the tumor on the native CT. RESULTS: The sensitivity for
      tumor detection was better for CE-CT (95%) than for native CT (83%) (p<0.001).
      Only mammographic visibility scores appeared to be significantly correlated with
      the visibility of the tumor on the native CT (p=0.013). CONCLUSION: In most
      patients CE is not required to visualize a known breast tumor. Mammographic
      visibility is a good parameter to decide on the use of CE.

PMID- 21741718
TI  - Hearing preservation after low dose linac radiosurgery for acoustic neuroma
      depends on initial hearing and time.
AB  - PURPOSE: To assess long term outcomes and factors determining hearing
      preservation after low dose linac stereotactic radiosurgery (SRS) for acoustic
      neuroma (AN) at the Royal Adelaide Hospital using prospectively collected data.
      MATERIAL AND METHODS: Between 1994 and 2010, 102 patients had SRS for AN. Five
      patients had neurofibromatosis type 2, six sporadic cases had relapsed after
      surgery, and the remaining 91 sporadic cases had primary SRS. Dose was 12 or 14
      Gy. Sustained changes >= 2 mm in any diameter were deemed significant, and useful
      hearing was defined as inter-aural pure tone average (PTA) <= 50 dB. Possible
      prognostic factors for hearing retention were tested by dividing the patients at
      pre-specified cutpoints: age (60 years), maximum tumour diameter (20mm), initial
      PTA (20 dB) and dose (12 vs 14 Gy). RESULTS: Eighty-four of the 91 sporadic
      primary SRS cases were evaluable for tumour control with at least one post
      treatment MRI. Their median follow-up was 65 mo (range 10-184 mo). Eighty-two
      (97.6%) were controlled, the remaining two requiring salvage surgery for
      progression at 5.75 and 9.75 years. Also, one of the post-operative cases
      required surgery at 2.1 years after SRS. For the 50 sporadic primary SRS patients
      with initially useful hearing, median age was 56 (range 21-76), median initial
      PTA 16 dB (range -11 to +45 dB) and median tumour diameter 21 mm (range 10-33
      mm). Four received 14 Gy, the rest 12 Gy. After SRS, 19 patients (38%) retained
      useful hearing. The Kaplan-Meier estimated preservation rate at 5 years was 50%
      (95% CI 36-64%) but by 10 years, this had fallen to 23% (95% CI 12-41%). On
      univariate analysis, the only significant factor was initial PTA (P < 0.0001).
      The estimated risk of hearing loss after SRS for patients with initial PTA >= 20
      dB was 5.0 (95% CI 2.2-11.2) times that with PTA < 20 dB. CONCLUSIONS: Tumour
      control was excellent (99/102=97% freedom from surgical salvage). Hearing
      preservation was strongly dependent on initial PTA, but there was a steady fall
      off in hearing out to at least 10 years.

PMID- 21741719
TI  - Superficial dose distribution in breast for tangential radiation treatment, Monte
      Carlo evaluation of Eclipse algorithms in case of phantom and patient geometries.
AB  - PURPOSE: The aim of this study is to examine experimentally and by the Monte
      Carlo method the accuracy of the Eclipse Pencil Beam Convolution (PBC) and
      Analytical Anisotropic Algorithm (AAA) algorithms in the superficial region (0-2
      cm) of the breast for tangential photon beams in a phantom case as well as in a
      number of patient geometries. The aim is also to identify differences in how the
      patient computer tomography data are handled by the treatment planning system and
      in the Monte Carlo simulations in order to reduce influences of these effects on
      the evaluation. MATERIALS AND METHODS: Measurements by thermoluminescent
      dosimeters and gafchromic film are performed for six MV tangential irradiation of
      the cylindrical solid water phantom. Tangential treatment of seven patients is
      investigated considering open beams. Dose distributions are obtained by the
      Eclipse PBC and AAA algorithms. Monte Carlo calculations are carried out by
      BEAMnrc/DOSXYZnrc code package. Calculations are performed with a calculation
      grid of 1.25*1.25*5 mm(3) for PBC and 2*2*5 mm(3) for AAA and Monte Carlo,
      respectively. Dose comparison is performed in both dose and spatial domains by
      the normalized dose difference method. RESULTS: Experimental profiles from the
      surface toward the geometrical center of the cylindrical phantom are obtained at
      the beam entrance and exit as well as laterally. Full dose is received beyond 2
      mm in the lateral superficial region and beyond 7 mm at the beam entrance. Good
      agreement between experimental, Monte Carlo and AAA data is obtained, whereas PBC
      is seen to underestimate the entrance dose the first 3-4 mm and the lateral dose
      by more than 5% up to 8 mm depth. In the patient cases considered, AAA and Monte
      Carlo show agreement within 3% dose and 4 mm spatial tolerance. PBC
      systematically underestimates the dose at the breast apex. The dimensions of
      region out of tolerance vary with the local breast shape. Different
      interpretations of patient boundaries in Monte Carlo and the Eclipse are found to
      influence the evaluation. Computer tomography marker wire may introduce local
      disturbance effects on the comparison as well. These factors are not related to
      the accuracy of the calculation algorithms and their effect is taken into account
      in the evaluation. CONCLUSIONS: The accuracy of AAA in the case of the solid
      water phantom is comparable with that of the Monte Carlo method. The AAA-Monte
      Carlo differences in the patient cases considered are within 3%, 4 mm tolerance.
      The PBC algorithm does not give equivalent results. In the phantom case, PBC
      underestimates the lateral dose by more than 5% up to 8 mm depth. The PBC-Monte
      Carlo differences in the patient cases are outside the tolerance at the breast
      apex. The dimension of region varies with the breast shape being typically 8-10
      mm long and 6-8 mm deep.

PMID- 21741720
TI  - Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus
      chemotherapy versus methotrexate in patients with recurrent or a second primary
      head and neck squamous cell carcinoma, treated with a palliative intent.
AB  - PURPOSE: This randomized phase III trial investigated the potential benefit of
      concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for
      patients treated with palliative intent for recurrent or second primary head and
      neck squamous cell carcinoma (HNSCC) in previously irradiated area. PATIENTS AND
      METHODS: Patients with recurrent HNSCC or a second primary not amenable to
      curative-intent treatment were randomized to the R-RT arm (concurrent re
      irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The
      primary endpoint was overall survival (OS). Due to a very slow accrual, the trial
      was closed after inclusion of 57 patients. RESULTS: Fifty-seven patients were
      included. All patients died in the two arms with a maximal follow-up of 5years.
      Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re
      irradiation did not improve OS compared with methotrexate (23% versus 22% at
      1year, NS). Sixteen patients experienced clinical grade ?3 late toxicities
      (>6months), 11 in R-RT arm and five in Ch-T arm. CONCLUSIONS: Premature
      discontinuation of the trial did not allow us to draw firm conclusions. However,
      there was no suggestion that concurrent re-irradiation, fluorouracil and
      hydroxyurea improved OS compared to methotrexate alone in patients treated with
      palliative intent for a recurrent or second primary HNSCC.

PMID- 21741721
TI  - Inclusion of clinical risk factors into NTCP modelling of late rectal toxicity
      after high dose radiotherapy for prostate cancer.
AB  - BACKGROUND AND PURPOSE: To fit an NTCP model including clinical risk factors to
      late rectal toxicities after radiotherapy for prostate cancer. METHODS AND
      MATERIALS: Data of 669 patients were considered. The probability of late toxicity
      within 36months (bleeding and incontinence) was fitted with the original and a
      modified Logit-EUD model, including clinical factors by fitting a subset specific
      TD(50)s: the ratio of TD(50)s with and without including the clinical variable
      was the dose-modifying factor (D(mod)). RESULTS: Abdominal surgery (surg) was a
      risk factor for G2-G3 bleeding, reflecting in a TD(50)=82.7Gy and 88.4Gy for
      patients with and without surg (D(mod)=0.94; 0.90 for G3 bleeding); acute
      toxicity was also an important risk factor for G2-G3 bleeding (D(mod)=0.93).
      Concerning incontinence, surg and previous diseases of the colon were the
      clinical co-factors. D(mod)(surg) and D(mod)(colon) were 0.50 and 0.42,
      respectively for chronic incontinence and 0.73 and 0.64, respectively for mean
      incontinence score ?1. Best-fit n values were 0.03-0.05 and 1 for bleeding and
      incontinence, respectively. The inclusion of clinical factors always improved the
      predictive value of the models. CONCLUSIONS: The inclusion of predisposing
      clinical factors improves NTCP estimation; the assessment of other clinical and
      genetic factors will be useful to reduce parameter uncertainties.

PMID- 21741722
TI  - Rhizosphere effect on survival of Escherichia coli O157:H7 and Salmonella
      enterica serovar Typhimurium in manure-amended soil during cabbage (Brassica
      oleracea) cultivation under tropical field conditions in Sub-Saharan Africa.
AB  - The effect of cabbage (Brassica oleracea) rhizosphere on survival of Escherichia
      coli O157:H7 and Salmonella Typhimurium in manure-amended soils under tropical
      field conditions was investigated in the Central Agro-Ecological Zone of Uganda.
      Three-week old cabbage seedlings were transplanted and cultivated for 120 days on
      manure-amended soil inoculated with 4 or 7 log CFU/g non-virulent E. coli O157:H7
      and S. Typhimurium. Cabbage rhizosphere did not affect survival of the 4log CFU/g
      inocula in manure-amended soil and the two enteric bacteria were not detected
      on/in cabbage leaves at harvest. The 7 log CFU/g E. coli O157:H7 and S.
      Typhimurium survived in bulk soil for a maximum of 80 and 96 days, respectively,
      but the organisms remained culturable in cabbage rhizosphere up to the time of
      harvest. At 7 log CFU/g inoculum, E. coli O157:H7 and S. Typhimurium
      contamination on cabbage leaves occurred throughout the cultivation period. Leaf
      surface sterilisation with 1% AgNO(3) indicated that the organisms were present
      superficially and in protected locations on the leaves. These results demonstrate
      that under tropical field conditions, cabbage rhizosphere enhances the
      persistence of E. coli O157:H7 and S. Typhimurium in manure-amended soil at high
      inoculum density and is associated with long-term contamination of the leaves.

PMID- 21741723
TI  - Visfatin is secreted into the breast milk and is correlated with weight changes
      of the infant after the birth.
AB  - INTRODUCTION: Visfatin is a recently identified adipokine with numerous metabolic
      and immunoregulatory properties that has been implicated in the regulation of the
      white adipose tissue (WAT) and significant changes in visfatin levels were
      reported during pregnancy. The aim of the study was to investigate dynamics of
      visfatin levels in maternal serum and human breast milk during a 180-d period
      after the delivery. MATERIALS AND METHODS: : Breast milk and venous blood samples
      were obtained from 24 healthy lactating women with uncomplicated, physiological
      pregnancy and appropriate-for-gestational age neonates and serum-milk sample duos
      were collected at the time of birth, at the 1-3, 12-14, 28-30, 88-90 and 178-180
      postpartum. RESULTS: Our study demonstrates that (1) visfatin is abundantly
      secreted into breast milk in humans, reaching approx. 100* higher concentrations
      compared to maternal serum; (2) visfatin concentrations in maternal serum show
      significant variations after the delivery and (3) visfatin concentration in
      colostrum could be used for prediction of the subsequent weight development
      (less/more severe weight loss during first 3 days after the birth) of the infant.
      DISCUSSION: Our data suggest that visfatin could play an important role in
      regulation of adiposity of the infant after the birth.

PMID- 21741724
TI  - Feedback to clinicians on preventable factors can reduce hospital onset
      Staphylococcus aureus bacteraemia rates.
AB  - Staphylococcus aureus bacteraemia (SAB) is associated with significant morbidity
      and mortality, yet there are limited data on preventable factors. This study
      aimed to evaluate SAB episodes at a tertiary care hospital; to identify factors
      that, if avoided, might have prevented the episode of SAB; and to provide
      feedback to treating clinicians. Of 187 episodes of SAB over 19 months 59.9% were
      caused by meticillin-susceptible S. aureus (MSSA) and 40.1% meticillin-resistant
      S. aureus (MRSA), 65.8% of SAB were healthcare-associated (HA) and 34.2% were
      community-acquired. Seven- and 30-day mortality rates, overall, were 11.2% and
      20.9% respectively. At least one preventable factor was identified in 50.4% of HA
      SAB episodes, including recent nosocomial MRSA acquisition in 53.7% MRSAB
      episodes and one or more factors associated with intravenous access in at least
      24.3% of HA (35.7% of hospital onset) cases. SAB was more likely to be associated
      with at least one identifiable, preventable factor in surgical than in medical
      inpatients (86.2% vs 54.5%, P=0.004). Patients with HA-MRSAB were more likely
      than those with HA-MSSAB to require intensive care unit admission (44.4% vs
      18.8%, P=0.003). Identifying and addressing preventable factors will better
      target resources for prevention of SAB. Feedback about preventable factors was
      associated with a reduction in HA-SAB rates from 0.29 to 0.20 per 1000 occupied
      bed-days, from 2008 to 2009.

PMID- 21741725
TI  - Screening of healthcare workers for meticillin-resistant Staphylococcus aureus:
      is it worth it?

PMID- 21741726
TI  - Protecting patients from harm: design and implementation of an institutional
      bloodborne pathogen protocol.
AB  - BACKGROUND: Patients are sometimes exposed to the blood of health care workers
      (HCWs) while receiving medical care. No national guidelines exist that
      authoritatively articulate the responsibility of HCWs infected with a potentially
      transmissible bloodborne pathogen (BBP). Geisinger Health System crafted and
      implemented a policy delineating the responsibilities of an HCW in the event of
      accidental blood exposure of a patient, specifically addressing HCWs known to be
      infected with a BBP. METHODS: In 2008, a multidisciplinary group convened to
      review available published resources from the American Medical Association,
      specialty society positions, state and national guidelines, Centers for Disease
      Control and Prevention, and Society for Healthcare Epidemiology, as well as
      selected commentaries. RESULTS: A policy was crafted and enacted within a large
      integrated heath care system that provided clear guidelines and responsibilities
      for HCWs who are either infected with a BBP or expose patients to blood in the
      course of providing medical care. This policy balances the rights of both
      patients and providers. CONCLUSIONS: The resources to devise policies regarding
      BBP exposure to patients are available but require distillation of complex
      scientific data and social and/or legal opinion or precedent. We offer Geisinger
      Health System's policy as a workable and readily accessible model that defines
      the obligations of providers to protect patients in the event of a BBP exposure.

PMID- 21741727
TI  - Attitudes and beliefs, not just knowledge, influence the effectiveness of
      environmental cleaning by environmental service workers.
AB  - BACKGROUND: Hospital environmental service workers (ESWs) play an important role
      in interrupting the chain of infection because the environment is a reservoir for
      nosocomial pathogens. Improving ESWs' knowledge through education has been shown
      to improve ESW cleaning, but the behavioral determinants of their work have not
      been studied. Understanding and targeting ESWs' attitudes and beliefs may inform
      strategies to improve environmental cleaning. METHODS: With the theory of planned
      behavior as framework, we used questionnaires and focus groups to examine
      intensive care unit ESWs' attitudes, beliefs [behavioral, normative, and
      control], and control) and intent about their job. Baseline quantitative
      microbial cultures of high-touch services were performed before and after
      cleaning. After an educational intervention addressing their attitudes, beliefs,
      and general infection control knowledge, attitudes, beliefs, and microbial
      contamination were reassessed. RESULTS: Beliefs were uniformly strong (4.5/5
      5/5), and normative beliefs correlated best with intent to clean (R(2) = 0.3).
      Themes elicited from the focus groups included "me versus them," lack of
      appreciation, pride in work, and "if it were me." The rate of environmental
      contamination was significantly improved after the intervention (P = .0074 vs P =
      .0023, respectively); the measured relationship among attitudes, beliefs, and
      intent was not significantly changed. CONCLUSION: ESWs' attitudes and beliefs
      about their job may impact their intent to clean and in turn the effectiveness of
      their efforts. Understanding and addressing these attitudes and beliefs can be
      used to inform strategies for sustained improvement of environmental cleaning.

PMID- 21741728
TI  - Infection control implications of influenza A and influenza B: coinfection or
      cocirculating strains?

PMID- 21741729
TI  - Apolipoprotein E genotypes and the risk of Parkinson disease.
AB  - We examined apolipoprotein E (ApoE) genotypes in relation to Parkinson's disease
      (PD) among 786 cases and 1537 controls, all non-Hispanic Caucasians. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic
      regression models, adjusting for year of birth, sex, smoking status, daily
      caffeine intake, and family history of PD. Compared with participants with ApoE
      epsilon33, epsilon4 carriers (epsilon34/epsilon44) had significantly lower odds
      for having PD (OR, 0.75; 95% CI, 0.59-0.94; p = 0.01), whereas epsilon2 carriers
      (epsilon23/epsilon22) did not (OR, 0.95; 95% CI, 0.73-1.24; p = 0.71). Subgroup
      analyses showed similar results. In addition, we conducted a meta-analysis which
      confirmed our primary findings (epsilon34/epsilon44 vs. epsilon33: OR, 0.90; 95%
      CI, 0.81-0.99; p = 0.024 and epsilon23/epsilon22 vs. epsilon33: OR, 1.10; 95% CI,
      0.97-1.23; p = 0.13). In PD patients, the prevalence of dementia appeared to be
      higher among epsilon4 carriers (compared with epsilon33: OR, 1.59; 95% CI, 0.98
      2.58; p = 0.06), but lower among epsilon2 carriers (OR, 0.75; 95% CI, 0.40-1.42;
      p = 0.38), although neither test was statistically significant. Our study
      suggested that the ApoE epsilon4 allele may be associated with a lower PD risk
      among non-Hispanic Caucasians.

PMID- 21741731
TI  - [Early fibrinolysis as an alternative in late detected acute ischemic stroke].

PMID- 21741732
TI  - Synthesis and identification of beta-aryloxyquinolines and their pyrano[3,2
      c]chromene derivatives as a new class of antimicrobial and antituberculosis
      agents.
AB  - A new class of beta-aryloxyquinolines 3a-i and their pyrano[3,2-c]chromene
      derivatives 6a-r incorporating a validated molecular target has been synthesized
      via a nucleophilic displacement and a one-pot multicomponent reaction
      respectively. In vitro antimicrobial activity of the synthesized compounds were
      investigated against a representative panel of pathogenic strains specifically
      Bacillus subtilis, Clostridium tetani, Streptococcus pneumoniae, Escherichia
      coli, Salmonella typhi, Vibrio cholera, Aspergillus fumigatus and Candida
      albicans. Compounds 3c, 3e, 3g, 6f, 6l and 6q exhibited excellent antibacterial
      activity while compound 6p exhibited more potent antifungal activity than that of
      first line standard drugs. In vitro antituberculosis activity was evaluated
      against Mycobacterium tuberculosis H37Rv and compound 6f is emerged as the
      promising antimicrobial member with better antitubercular activity. Majority of
      the compounds appears to be better antimicrobials but poor antituberculars.

PMID- 21741733
TI  - [Lipoatrophia semicircularis: a case report].
AB  - We report a 54-year-old man who presented bilateral, symmetric depressions on the
      anterior aspect of his thighs corresponding to lipoatrophia semicircularis. The
      origin of this distinctive variant of lipoatrophy is unknown. Repeated external
      microtraumatisms were considered to be the most plausible explanation. Recently,
      as many recently affected subjects shared a status of administrative employee,
      the role of electromagnetic fields generated by computers and their wirings has
      been discussed. Prevention proposal includes adapting work environment related to
      the use of computerized devices.

PMID- 21741734
TI  - Postprandial protein metabolism but not a fecal test reveals protein
      malabsorption in patients with pancreatic exocrine insufficiency.
AB  - BACKGROUND & AIMS: Pancreatic exocrine insufficiency (PEI) impairs fat
      absorption, but few data are available on protein absorption. We investigated
      this question in patients with chronic pancreatitis, both in the absence and
      presence of enzyme therapy, using a stable isotope sensitive method. METHODS:
      Eleven patients with sustained PEI and regular enzyme substitution were
      investigated at hospital, after a washout period without enzyme substitution, and
      later after reintroduction of substitution. The digestibility and postprandial
      metabolism of dietary protein were characterized after the ingestion of a semi
      synthetic single meal containing 20 g (15)N-labeled casein. RESULTS: At baseline,
      20 +/- 8% of dietary nitrogen was transferred to the metabolic pools vs. 24.5 +/-
      7% under enzyme treatment (P = 0.04). After treatment, the transfer of dietary
      nitrogen tended to increase in plasma amino acids, and increased significantly in
      plasma proteins and the deamination pool. In contrast, the fecal excretion of
      dietary nitrogen did not demonstrate any treatment effect. In patients not
      receiving insulin for diabetes, the treatment stimulated insulin secretion.
      CONCLUSIONS: Protein malabsorption was mostly undetectable using standard fecal
      tests. The study of the postprandial fate of dietary protein revealed a moderate
      increase of its transfer to metabolic pools after enzyme substitution.

PMID- 21741735
TI  - Biomechanical analysis of total elbow replacement with unlinked iBP prosthesis:
      an in vitro and finite element analysis.
AB  - BACKGROUND: Numerous models of elbow prostheses are being used and can be divided
      into two categories: one being a semi-constrained, linked type; and the other
      being non-constrained, unlinked type. Recent reports of National Elbow
      Arthroplasty Registers reveal no significant differences in the survival rates
      between linked and unlinked prosthesis brands, and the main cause appointed for
      revision for both types is loosening. Some previous biomechanical studies confirm
      the presence of abnormal bone stresses for the linked type, which can be
      associated with the risk of loosening. However for the unlinked type,
      biomechanical studies are not available that corroborate a loosening risk. It
      seems, that issue has not yet been fully answered and requires further analysis.
      METHODS: Cortex strains adjacent to the elbow joint were measured with strain
      gauges in synthetic humeri and ulnae, before and after replacement. To assess
      cancellous bone strains and cement stresses around the implant finite element
      models validated relative to measured strains were used. FINDINGS: Bone strains
      adjacent to the implant tip increased several times in the humerus and ulna. At
      the epiphyseal regions a generalised cancellous bone strain reduction was
      observed for both humerus and ulna relatively to the intact bones.
      INTERPRETATION: The unlinked elbow prostheses can be associated with the risk of
      bone fatigue failure by overload, particularly in the ulna, and bone resorption
      by stress-shielding at the epiphyseal regions. The identical structural behaviour
      relative to linked prostheses associated with the same loosening risks
      corroborates the results of recent arthroplasty published register reports.

PMID- 21741736
TI  - Enhanced nitrogen deposition exacerbates the negative effect of increasing
      background ozone in Dactylis glomerata, but not Ranunculus acris.
AB  - The combined impacts of simulated increased nitrogen (N) deposition (75 kg Nha(
      1)yr (-1)) and increasing background ozone (O(3)) were studied using two
      mesotrophic grassland species (Dactylis glomerata and Ranunculus acris) in
      solardomes, by means of eight O(3) treatments ranging from 15.5 ppb to 92.7 ppb
      (24h average mean). A-C(i) curves were constructed for each species to gauge
      effects on photosynthetic efficiency and capacity, and effects on biomass
      partitioning were determined after 14 weeks. Increasing the background
      concentration of O(3) reduced the healthy above ground and root biomass of both
      species, and increased senesced biomass. N fertilisation increased biomass
      production in D. glomerata, and a significantly greater than additive effect of
      O(3) and N on root biomass was evident. In contrast, R. acris biomass was not
      affected by high N. The study shows the combined effects of these pollutants have
      differential implications for carbon allocation patterns in common grassland
      species.

PMID- 21741737
TI  - Who gains, who loses and how: leveraging gender and class intersections to secure
      health entitlements.
AB  - This paper argues that a focus on the middle groups in a multi-dimensional
      socioeconomic ordering can provide valuable insights into how different axes of
      advantage and disadvantage intersect with each other. It develops the elements of
      a framework to analyse the middle groups through an intersectional analysis, and
      uses it to explore how such groups leverage economic class or gender advantages
      to secure entitlements to treatment for long-term illness. The study draws upon
      household survey data on health-seeking for long-term ailments from 60 villages
      of Koppal district, Karnataka (India). The survey was designed to capture gender,
      economic class, caste, age and life stage-based inequalities in access to health
      care during pregnancy and for short and long-term illnesses. There were striking
      similarities between two important middle groups--non-poor women and poor men--in
      some key outcomes: their rates of non-treatment when ill, treatment
      discontinuation and treatment continuation, and the amounts they spent for
      treatment. These two groups are the obverse of each other in terms of gender and
      economic class advantage and disadvantage. Non-poor women have an economic
      advantage and a gender disadvantage, while poor men have the exact opposite.
      However, despite the similarities in outcomes, the processes by which gender and
      class advantage were leveraged by each of the groups varied sharply. Similar
      patterns held for the poorest men except that the class disadvantage they had to
      overcome was greater, and the results are modified by this.

PMID- 21741739
TI  - Surgical treatment for nontuberculous mycobacterial (NTM) cervicofacial
      lymphadenitis in children.
AB  - PURPOSE: To compare surgical excision with surgical curettage in the treatment of
      nontuberculous mycobacterial (NMT) cervicofacial lymphadenitis in children.
      PATIENTS AND METHODS: Fifty children, 22 boys and 28 girls, with a PCR- or
      cultured-confirmed diagnosis of cervicofacial NTM infection were included in the
      study. Twenty-five children were randomized to surgical excision of the involved
      lymph nodes, and 25 children to surgical curettage. RESULTS: The median age of
      the children was 36 months (range, 14-120 months). All children had a red,
      fluctuating lymphadenitis, and there were no marked differences between the
      treatment groups with respect to mean duration of lymph node swelling before
      presentation, location, and the size of the lymph node swelling. Most (84%) of
      the involved nodes were located in the submandibular region and 6% were located
      in the preauricular region. Multiple locations (both preauricular and
      submandibular) were observed in the remaining 10%. Mycobacterium avium (74%) and
      Mycobacterium haemophilum (22%) were the predominant NTM species. Mean wound
      healing time for the excision group was 3.6 +/- 1.2 weeks versus 11.4 +/- 5.1
      weeks for the curettage group (P <= .05). Postoperative transient marginal
      mandibular nerve weakness of the facial nerve was seen in 4 patients (16%) of the
      excision group. In all these patients the function of the nerve returned to
      normal within 12 weeks. No facial nerve problems were observed in the curettage
      group. Postoperative infections were not observed. CONCLUSIONS: Surgical excision
      leads to a quick resolution of NTM cervicofacial lymphadenitis. Curettage leads
      to delayed healing but might be considered as an alternative if excision of the
      necrotized lymph nodes is technically difficult in cases of adherence of the
      facial nerve branche.

PMID- 21741740
TI  - Safe harvesting of outer table parietal bone grafts using an oscillating saw and
      a bone scraper: a refinement of technique for harvesting cortical and
      "cancellous"-like calvarial bone.
AB  - Calvarial bone is a readily available source of bone for preimplantation
      augmentation procedures of the alveolar process. However, the calvaria consist
      mostly of cortical bone, and cancellous bone of the diploic space is scarce. A
      bone scraper (Safescraper Twist; META, Reggio Emilia, Italy) was used to create a
      beveled trough around the calvarial outer table graft to facilitate its removal
      with an oscillating saw. Using the scraper, copious amounts (>10 mL) of
      "cancellous"-like bone could be collected. This new application of the
      Safescraper Twist obviated milling down additional cortical pieces.

PMID- 21741741
TI  - Bone regeneration without bone grafting after resection of a segment of the
      mandible to treat bisphosphonate-related osteonecrosis of the jaw.

PMID- 21741742
TI  - Venous anastomoses using microvascular coupler in free flap head and neck
      reconstruction.
AB  - PURPOSE: This study is a retrospective review of the experience using the venous
      coupler for head and neck reconstruction over a 3-year period at the University
      of Maryland Medical Center, Department of Oral and Maxillofacial Surgery.
      MATERIALS AND METHODS: One hundred seventy-eight consecutive cases of
      microvascular free flaps between May 2007 and September 2010 were retrospectively
      reviewed. Data were collected by demographic information, flap type, recipient
      vessels, method of anastomosis, coupler size, coupler orientation, complications
      associated with coupler, and reconstruction results. Fisher exact test was used
      for statistical analysis. RESULTS: There were 294 anastomotic coupler devices
      used in 173 flaps, with hand-sewn venous anastomoses performed in 5 patients. The
      overall flap success rate was 94.9% (169/178). Success rate among cases in which
      the coupler was used was 95.4% (8/173). Total coupler venous thrombosis rate was
      4.0% (7/173), with a statistically significant difference (P < .05) in reference
      to the number of venous anastomoses performed: 58 cases had a single vein
      anastomosed, 5 cases developed thrombosis; while the 115 flaps with 2 venous
      anastomoses, only 2 cases had thrombosis. CONCLUSIONS: The microvascular coupler
      is reliable for venous anastomosis in free flap head and neck reconstruction;
      dual-vein anastomoses appear to have better results than single-vein anastomoses.
      Flow coupler has a promising utility in monitoring buried flaps and flaps that
      are difficult to observe. The microvascular coupler deserves to be more commonly
      used in free flap head and neck reconstruction.

PMID- 21741743
TI  - The adult suicide-prone patient: a review of the medical literature and
      implications for oral and maxillofacial surgeons.
AB  - PURPOSE: Suicide is the 11th most common cause of death among American adults.
      Some individuals who commit suicide may have been treated by oral and
      maxillofacial surgeons in the days preceding the event. Because suicide often is
      preventable, in this report we review methods that are useful in identifying
      individuals at risk of imminent suicide and give suggestions for obtaining
      interventional assistance. METHODS: A Medline search using the key terms
      "suicide," "adult," and "oral surgery" was conducted. Articles selected were
      published in peer-reviewed journals. RESULTS: Individuals who have told their
      surgeon they have no further reason to live, have developed a suicide plan, have
      secured a lethal device, and have previously made such an attempt are at extreme
      risk and require immediate intervention. Additional risk factors include being
      white, aged older than 45 years, and unemployed; living alone, with poor social
      supports; having a current mental illness or history of mental illness, including
      substance abuse; and having a family history of suicide. Specialty-specific
      patients at highest risk are those treated for oral cancer and cosmetic issues
      and those with adverse surgical outcomes. With regard to assessment of these
      individuals, the modified SAD PERSONS acronym can assist surgeons in documenting
      the presence of major risk factors associated with adult suicide and in
      facilitating communication with emergency personnel. CONCLUSIONS: Suicide is a
      potentially preventable public health problem. Oral and maxillofacial surgeons
      can be key in elucidating clinically significant suicide potential in their
      patients and referring them for timely intervention.

PMID- 21741744
TI  - Pigmented villonodular synovitis of the temporomandibular joint presenting as a
      middle cranial fossa tumor.

PMID- 21741745
TI  - Good news for those resuscitated from out-of-hospital cardiac arrest.

PMID- 21741746
TI  - Community extracorporeal life support for cardiac arrest - when should it be
      used?

PMID- 21741747
TI  - Mifepristone in combination with prostaglandins for termination of 10-16 weeks'
      gestation: a systematic review.
AB  - OBJECTIVES: Medical regimens using mifepristone in combination with
      prostaglandins have been widely available for women undergoing termination of
      pregnancy (TOP) at 10-16 weeks' gestation in China. We undertook a systematic
      review to compare different regimens of mifepristone with prostaglandins for TOP
      at 10-16 weeks' gestation. METHODS: We searched multiple electronic databases for
      English and Chinese language reports (1990-2007) including MEDLINE, the Cochrane
      Library and the Chinese Biomedical Literature Database. Included were trials
      comparing mifepristone with prostaglandins (misoprostol, gemeprost or carboprost
      (PG05)) to each other for women at 10-16 weeks' gestation. Outcomes were
      successful abortion rates, induction-to-expulsion time, blood loss and side
      effects. Data were processed with RevMan 5 software. RESULTS: Nineteen trials
      comparing mifepristone with prostaglandin (misoprostol and PG05) were found of
      which 14 contributed to meta-analyses (4206 women). The quality of reports was
      poor. The effectiveness of vaginal mifepristone/misoprostol was super than
      mifepristone/PG05 (RR 1.14, 95%CI 1.05-1.22) as was induction-to-expulsion time,
      blood loss and side effects. When comparing misoprostol/mifepristone 150mg to
      misoprostol/mifepristone 200mg, no difference in TOP success rates were found (RR
      0.98, 95%CI 0.96-1.01). Misoprostol vaginally compared to orally significantly
      increased the TOP success rate (RR 1.12, 95%CI 1.01-1.24). Gastrointestinal
      symptoms and fever occurred more often in misoprostol oral group (RR 1.67, 95%CI
      1.46-1.91). CONCLUSIONS: Medical regimens of mifepristone/prostaglandins were
      effective and safe for TOP at 10-16 weeks' gestation. Misoprostol was super than
      PG05, and misoprostol vaginally was found to have better effectiveness than
      misoprostol orally. Further research should evaluate the relative effectiveness
      of medical methods compared to surgery.

PMID- 21741748
TI  - Single-port versus conventional laparoscopic salpingectomy in tubal pregnancy: a
      comparison of surgical outcomes.
AB  - OBJECTIVE: To compare the surgical outcomes of single-port laparoscopic
      salpingectomy (SPLS) and conventional laparoscopic salpingectomy for the surgical
      treatment of tubal pregnancy. STUDY DESIGN: From January to June 2009, patients
      with tubal pregnancy were assigned to two surgical groups: SPLS and conventional
      laparoscopic salpingectomy. Surgical outcomes, including operative time,
      postoperative haemoglobin drop, hospital stay and complications, were compared
      prospectively. For SPLS, a novel multichannel port was made using a wound
      retractor and a surgical glove. RESULTS: In total, 60 patients were enrolled in
      the study (30 in the SPLS group and 30 in the conventional group). All operations
      were completed successfully. No significant difference was observed between the
      two groups in terms of mean operative time (52.6 +/- 16.1 min vs 46.8 +/- 16.2
      min; p=0.174), mean difference between pre- and postoperative haemoglobin (1.7 +/
      0.8 g/dl vs 1.8 +/- 1.0 g/dl; p=0.636), or mean postoperative hospital stay (2.4
      +/- 0.5 days vs 2.4 +/- 0.9 days; p=1.000). No complications were encountered in
      either group, and there was no conversion to conventional laparoscopy in the SPLS
      group. CONCLUSION: SPLS has comparable surgical outcomes to conventional
      laparoscopic salpingectomy for the surgical treatment of tubal pregnancy in terms
      of operative time, hospital stay and complication rates. However, further studies
      are needed to evaluate the merits expected of single-port laparoscopic surgery,
      such as cosmetic advantage and decreased pain in patients.

PMID- 21741749
TI  - Porcine small intestinal submucosa implant in pubovaginal sling procedure on 48
      consecutive patients: long-term results.
AB  - OBJECTIVE: The long-term efficacy of pubovaginal sling (PVS) procedure with
      porcine small intestinal submucosa (SIS) implant was retrospectively assessed.
      STUDY DESIGN: Forty-eight patients with SUI underwent a pubovaginal sling with
      SIS. Patient evaluation included history, physical examination with stress test
      and prolapse assessment by Baden-Walker classification, routine laboratory tests,
      24h-pad test, and multichannel urodynamic measurement. Postoperatively the
      patients were classified as cured, improved and unchanged or failed. A King's
      Health Questionnaire (KHQ) was performed to verify post-operatively the quality
      of life of these patients. RESULTS: At median follow-up of 76 months 33/48 (69%)
      were cured, 6/48 (12%) were improved while 9/48 (19%) were failed or unchanged.
      No urinary retention or dyspareunia was reported and no vaginal erosion or
      adverse tissue reaction was detected. The descriptive statistics of KHQ scores by
      dimensions was done in 32/48 patients (67%). Failed or unchanged patients showed
      worse scores than cured and improved patients in all KHQ dimensions showing an
      overall overlapping between objective and subjective results although these
      findings are weakened due to the lack of a preoperative evaluation of QoL.
      CONCLUSIONS: PVS procedure using SIS cannot offer a durable option for the
      treatment of SUI as reported by the current mininvasive techniques.

PMID- 21741750
TI  - Lambert-Eaton myasthenic syndrome associated with intravascular uterine
      leiomyoma.

PMID- 21741751
TI  - Colonoscopy-assisted reposition of the incarcerated uterus in mid-pregnancy: a
      report of four cases and a literature review.
AB  - The treatment of mid-gestational uterine incarceration remains a challenge. The
      success rate of manual reduction decreases with gestational age, and an operative
      procedure may carry important fetal, next to possible maternal morbidities. We
      will present four cases of uterine incarceration between the 15th and 25th week
      of pregnancy of which three colonoscopy-assisted manual repositions proved
      successful. It illustrates that conservative treatment of uterine incarceration
      is feasible, even during the late second trimester. That is why a review of the
      conservative approach of this rare condition is also presented.

PMID- 21741752
TI  - Difference in sleep quality between premenopause and postmenopause according to
      depression screening.

PMID- 21741753
TI  - A biophysical model of intracellular distribution and perinuclear accumulation of
      particulate matter.
AB  - We have measured in human alveolar cells the cytoplasmic distribution of the
      fluorophore coumarin-6 carried by Solid Lipid Nanoparticles (SLNs) and observed a
      perinuclear accumulation of the fluorescence that can be described by a single
      exponential growth along an ideal line joining the plasma membrane to the nuclear
      border and by a sigmoidal relationship as a function of time. Intracellular
      distribution was affected by lowering the temperature from 37 to 4 degrees  C and
      by the disruption of cytoskeleton by cytochalasin D, but it was minimally
      perturbed by the inhibition of ATP dependent molecular motors. A biophysical
      model was developed for an accumulation of loaded particles against a diffusion
      gradient based on a mean field interaction energy, whose origin we ascribe to the
      actin structure of the cytoskeleton. The estimated value for the load diffusion
      coefficient was four and two orders of magnitude less than that of free coumarin
      6 and of SLNs in aqueous solutions, respectively, suggesting that the load moves
      within the cell cytoplasm in a form still reminiscent of the nanocarrier
      structure.

PMID- 21741754
TI  - Global architecture of human poly(A)-specific ribonuclease by atomic force
      microscopy in liquid and dynamic light scattering.
AB  - Deadenylation is the initial and often rate-limiting step in the main pathways of
      eukaryotic mRNA decay. Poly(A)-specific ribonuclease (PARN) is a eukaryotic
      enzyme that efficiently degrades mRNA poly(A) tails. Structural and functional
      studies have shown that human PARN is composed of at least three functional
      domains, i.e. the catalytic nuclease domain and two RNA binding domains, the R3H
      and the RNA recognition motif (RRM), respectively. However, the complete
      structure of the full length protein is still unknown. We have investigated the
      global architecture of human PARN by atomic force microscopy (AFM) imaging in
      buffered milieu and report for the first time the dimensions of the full length
      protein at subnanometer resolution. The AFM images of single PARN molecules
      reveal compact ellipsoidal dimers (10.9 * 7.6 * 4.6nm). The dimeric form of PARN
      was confirmed by dynamic light scattering (DLS) measurements that rendered a
      molecular weight of 161 kDa, in accordance with previous crystal structures of
      PARN fragments showing a dimeric composition. We discuss a putative internal
      arrangement of three functional domains within the full length PARN dimer.

PMID- 21741755
TI  - The real water consumption behind drinking water: the case of Italy.
AB  - The real amount of drinking water available per capita is a topic of great
      interest for human health and the economic and political management of resources.
      The global market of bottled drinking water, for instance, has shown exponential
      growth in the last twenty years, mainly due to reductions in production costs and
      investment in promotion. This paper aims to evaluate how much freshwater is
      actually consumed when water is drunk in Italy, which can be considered a mature
      bottled-water market. A Water Footprint (WF) calculation was used to compare the
      alternatives: bottled and tap water. Six Italian brands of water sold in PET
      bottles were inventoried, analysed and compared with the public tap water of the
      city of Siena, as representative of the Italian context. Results showed that more
      than 3 L of water were needed to provide consumers with 1.50 L of drinking water.
      In particular, a volume of 1.50 L of PET-bottled water required an extra virtual
      volume of 1.93 L of water while an extra 2.13 L was necessary to supply the same
      volume of tap water. These values had very different composition and origin. The
      WF of tap water was mainly due to losses of water during pipeline distribution
      and usage, while WF of bottled water was greatly influenced by the production of
      plastic materials. When the contribution of cooling water was added to the
      calculation, the WF of bottled water rose from 3.43 to 6.92 L. Different
      strategies to reduce total water footprint are discussed.

PMID- 21741756
TI  - Use of several waste substrates for carotenoid-rich yeast biomass production.
AB  - Carotenoids are industrially significant pigments produced in many bacteria,
      fungi, and plants. Carotenoid biosynthesis in yeasts is involved in stress
      response mechanisms. Thus, controlled physiological and nutrition stress can be
      used for enhanced pigment production. Huge commercial demand for natural
      carotenoids has focused attention on developing of suitable biotechnological
      techniques including use of liquid waste substrates as carbon and/or nitrogen
      source. In this work several red yeast strains (Sporobolomyces roseus,
      Rhodotorula glutinis, Rhodotorula mucilaginosa) were enrolled into a comparative
      screening study. To increase the yield of these pigments at improved biomass
      production, several types of exogenous as well as nutrition stress were tested.
      Each strain was cultivated at optimal growth conditions and in medium with
      modified carbon and nitrogen sources. Synthetic media with addition of complex
      substrates (e.g. yeast extract) and vitamin mixtures as well as some waste
      materials (whey, potato extract) were used as nutrient sources. Peroxide and salt
      stress were applied too. The production of carotene enriched biomass was carried
      out in flasks as well as in laboratory fermentor. The best production of biomass
      was obtained in inorganic medium with yeast extract. In optimal conditions tested
      strains differ only slightly in biomass production. All strains were able to use
      most of waste substrates. Biomass and pigment production was more different
      according to substrate type. In laboratory fermentor better producers of enriched
      biomass were both Rhodotorula strains. The highest yields were obtained in R.
      glutinis CCY 20-2-26 cells cultivated on whey medium (cca 45 g per liter of
      biomass enriched by 46 mg/L of beta-carotene) and in R. mucilaginosa CCY 20-7-31
      grown on potato medium and 5% salt (cca 30 g per liter of biomass enriched by 56
      mg/L of beta-carotene). Such dried carotenoid-enriched red yeast biomass could be
      directly used in feed industry as nutrition supplement.

PMID- 21741757
TI  - Landscape--wildfire interactions in southern Europe: implications for landscape
      management.
AB  - Every year approximately half a million hectares of land are burned by wildfires
      in southern Europe, causing large ecological and socio-economic impacts. Climate
      and land use changes in the last decades have increased fire risk and danger. In
      this paper we review the available scientific knowledge on the relationships
      between landscape and wildfires in the Mediterranean region, with a focus on its
      application for defining landscape management guidelines and policies that could
      be adopted in order to promote landscapes with lower fire hazard. The main
      findings are that (1) socio-economic drivers have favoured land cover changes
      contributing to increasing fire hazard in the last decades, (2) large wildfires
      are becoming more frequent, (3) increased fire frequency is promoting homogeneous
      landscapes covered by fire-prone shrublands; (4) landscape planning to reduce
      fuel loads may be successful only if fire weather conditions are not extreme. The
      challenges to address these problems and the policy and landscape management
      responses that should be adopted are discussed, along with major knowledge gaps.

PMID- 21741758
TI  - Beyond the conventional: meeting the challenges of landscape governance within
      the European Landscape Convention?
AB  - Academics and policy makers seeking to deconstruct landscape face major
      challenges conceptually, methodologically and institutionally. The meaning(s),
      identity(ies) and management of landscape are controversial and contested. The
      European Landscape Convention provides an opportunity for action and change set
      within new governance agendas addressing interdisciplinarity and spatial
      planning. This paper critically reviews the complex web of conceptual and
      methodological frameworks that characterise landscape planning and management and
      then focuses on emerging landscape governance in Scotland within a mixed method
      approach involving policy analyses, semi-structured interviews and best practice
      case studies. Using Dower's (2008) criteria from the Articles of the European
      Landscape Convention, the results show that whilst some progress has been made in
      landscape policy and practice, largely through the actions of key individuals and
      champions, there are significant institutional hurdles and resource limitations
      to overcome. The need to mainstream positive landscape outcomes requires a
      significant culture change where a one-size-fits-all approach does not work.

PMID- 21741759
TI  - Temperature-dependent differences in the nonlinear acoustic behavior of
      ultrasound contrast agents revealed by high-speed imaging and bulk acoustics.
AB  - Previous work by the authors has established that increasing the temperature of
      the suspending liquid from 20 degrees C to body temperature has a significant
      impact on the bulk acoustic properties and stability of an ultrasound contrast
      agent suspension (SonoVue, Bracco Suisse SA, Manno, Lugano, Switzerland). In this
      paper the influence of temperature on the nonlinear behavior of microbubbles is
      investigated, because this is one of the most important parameters in the context
      of diagnostic imaging. High-speed imaging showed that raising the temperature
      significantly influences the dynamic behavior of individual microbubbles. At body
      temperature, microbubbles exhibit greater radial excursion and oscillate less
      spherically, with a greater incidence of jetting and gas expulsion, and therefore
      collapse, than they do at room temperature. Bulk acoustics revealed an associated
      increase in the harmonic content of the scattered signals. These findings
      emphasize the importance of conducting laboratory studies at body temperature if
      the results are to be interpreted for in vivo applications.

PMID- 21741760
TI  - Basic research in kidney cancer.
AB  - CONTEXT: Advances in basic research will enhance prognosis, diagnosis, and
      treatment of renal cancer patients. OBJECTIVE: To discuss advances in our
      understanding of the molecular basis of renal cancer, targeted therapies, renal
      cancer and immunity, and genetic factors and renal cell carcinoma (RCC). EVIDENCE
      ACQUISITION: Data on recently published (2005-2011) basic science papers were
      reviewed. EVIDENCE SYNTHESIS: Advances in basic research have shown that renal
      cancers can be subdivided based on specific genetic profiles. Now that this
      molecular basis has been established, it is becoming clear that additional events
      play a major role in the development of renal cancer. For example, aberrant
      chromatin remodelling appears to be a main driving force behind tumour
      progression in clear cell RCC. A large number of potential biomarkers have
      emerged using various high-throughput platforms, but adequate biomarkers for RCC
      are still lacking. To bring the potential biomarkers and biomarker profiles to
      the clinical arena is a major challenge for the field. The introduction of
      tyrosine kinase inhibitors (TKIs) for therapy has shifted the interest away from
      immunologic approaches. Nevertheless, a wealth of evidence supports immunotherapy
      for RCC. Interestingly, studies are now appearing that suggest a combination of
      TKI and immunotherapy may be beneficial. Thus far, little attention has been paid
      to patient-specific differences. With high-throughput methods becoming cheaper
      and with the advances in sequencing possibilities, this situation is expected to
      change rapidly. CONCLUSIONS: Great strides have been made in the understanding of
      molecular mechanisms of RCC. This has led this field to the enviable position of
      having a range of molecularly targeted therapies. Large sequencing efforts are
      now revealing more and more genes responsible for tumour development and
      progression, offering new targets for therapy. It is foreseen that through
      integration of high-throughput platforms, personalised cancer treatment for RCC
      patients will become possible.

PMID- 21741761
TI  - The epidemiology of renal cell carcinoma.
AB  - CONTEXT: Kidney cancer is among the 10 most frequently occurring cancers in
      Western communities. Globally, about 270 000 cases of kidney cancer are diagnosed
      yearly and 116 000 people die from the disease. Approximately 90% of all kidney
      cancers are renal cell carcinomas (RCC). OBJECTIVE: The causes of RCC are not
      completely known. We have reviewed known aetiologic factors. EVIDENCE
      ACQUISITION: The data provided in the current review are based on a thorough
      review of available original and review articles on RCC epidemiology with a
      systemic literature search using Medline. EVIDENCE SYNTHESIS: Smoking, overweight
      and obesity, and germline mutations in specific genes are established risk
      factors for RCC. Hypertension and advanced kidney disease, which makes dialysis
      necessary, also increase RCC risk. Specific dietary habits and occupational
      exposure to specific carcinogens are suspected risk factors, but results in the
      literature are inconclusive. Alcohol consumption seems to have a protective
      effect for reasons yet unknown. Hardly any information is available for some
      factors that may have a high a priori role in the causation of RCC, such as salt
      consumption. CONCLUSIONS: Large collaborative studies with uniform data
      collection seem to be necessary to elucidate a complete list of established risk
      factors of RCC. This is necessary to make successful prevention possible for a
      disease that is diagnosed frequently in a stage where curative treatment is not
      possible anymore.

PMID- 21741762
TI  - Cancer-specific and other-cause mortality after radical prostatectomy versus
      observation in patients with prostate cancer: competing-risks analysis of a large
      North American population-based cohort.
AB  - BACKGROUND: Initial treatment options for low-risk clinically localized prostate
      cancer (PCa) include radical prostatectomy (RP) or observation. OBJECTIVE: To
      examine cancer-specific mortality (CSM) after accounting for other-cause
      mortality (OCM) in PCa patients treated with either RP or observation. DESIGN,
      SETTING, AND PARTICIPANTS: Using the Surveillance Epidemiology and End Results
      Medicare-linked database, a total of 44 694 patients >=65 yr with localized
      (T1/2) PCa were identified (1992-2005). INTERVENTION: RP and observation.
      MEASUREMENTS: Propensity-score matching was used to adjust for potential
      selection biases associated with treatment type. The matched cohort was randomly
      divided into the development and validation sets. Competing-risks regression
      models were fitted and a competing-risks nomogram was developed and externally
      validated. RESULTS AND LIMITATIONS: Overall, 22,244 (49.8%) patients were treated
      with RP versus 22450 (50.2%) with observation. Propensity score-matched analyses
      derived 11,669 matched pairs. In the development cohort, the 10-yr CSM rate was
      2.8% (2.3-3.5%) for RP versus 5.8% (5.0-6.6%) for observation (absolute risk
      reduction: 3.0%; relative risk reduction: 0.5%; p<0.001). In multivariable
      analyses, the CSM hazard ratio for RP was 0.48 (0.38-0.59) relative to
      observation (p<0.001). The competing-risks nomogram discrimination was 73% and
      69% for prediction of CSM and OCM, respectively, in external validation. The
      nature of observational data may have introduced a selection bias. CONCLUSIONS:
      On average RP reduces the risk of CSM by half in patients aged >=65 yr, relative
      to observation. The individualized protective effect of RP relative to
      observation may be quantified with our nomogram.

PMID- 21741763
TI  - Gut microbiota and probiotics in colon tumorigenesis.
AB  - The human gastrointestinal tract harbors a complex and abundant microbial
      community reaching as high as 10(13)-10(14) microorganisms in the colon. This
      endogenous microbiota forms a symbiotic relationship with their eukaryotic host
      and this close partnership helps maintain homeostasis by performing essential and
      non-redundant tasks (e.g. nutrition/energy and, immune system balance, pathogen
      exclusion). Although this relationship is essential and beneficial to the host,
      various events (e.g. infection, diet, stress, inflammation) may impact microbial
      composition, leading to the formation of a dysbiotic microbiota, further
      impacting on health and disease states. For example, Crohn's disease and
      ulcerative colitis, collectively termed inflammatory bowel diseases (IBD), have
      been associated with the establishment of a dysbiotic microbiota. In addition,
      extra-intestinal disorders such as obesity and metabolic syndrome are also
      associated with the development of a dysbiotic microbiota. Consequently, there is
      an increasing interest in harnessing the power of the microbiome and modulating
      its composition as a means to alleviate intestinal pathologies/disorders and
      maintain health status. In this review, we will discuss the emerging relationship
      between the microbiota and development of colorectal cancer as well as present
      evidence that microbial manipulation (probiotic, prebiotic) impacts disease
      development.

PMID- 21741764
TI  - Genotypic dependent effect of exogenous glutathione on Cd-induced changes in
      proteins, ultrastructure and antioxidant defense enzymes in rice seedlings.
AB  - Greenhouse hydroponic experiments were conducted using Cd-sensitive (cv.
      Xiushui63) and tolerant (Bing97252) rice genotypes to evaluate how different
      genotypes responded to Cd toxicity in presence of glutathione (GSH). Results
      showed that GSH alleviates Cd-toxicity, ameliorates Cd-induced damages on
      leaf/root ultrastructures. Nine proteins in roots were identified, using 2-DE
      coupled with mass spectrometry, whose expression were down-regulated in
      Xiushui63, up-regulated/unchanged in Bing97252 by Cd; coinstantaneously
      enhanced/unchanged in Cd+GSH over Cd alone treatment in both genotypes. They are
      l-ascorbate peroxidase, putative short-chain dehydrogenase/reductase, Glycolipid
      transfer protein, elongation factor, Os04g0652700, carbonic anhydrase,
      Os08g0374000, chitinase, and putative disease resistance response protein. Eight
      proteins in leaves with expression of increase in Bing97252 but down
      regulate/unchange in Xiushui63, categorized as four groups of their functions:
      carbon metabolism, TCA cycle, photorespiration and RNA processing. Furthermore,
      we identified eight proteins with repressed expression in Cd-treated and up
      regulated in Cd+GSH-treated rice leaves of Xiushui63.

PMID- 21741765
TI  - Investigation of a sewage-integrated technology combining an expanded granular
      sludge bed (EGSB) and an electrochemical reactor in a pilot-scale plant.
AB  - A sewage-integrated treatment system (SITS) for the treatment of municipal
      wastewater, consisting of an expanded granular sludge bed (EGSB) reactor to
      remove soluble organic matter and an electrochemical (EC) reactor to oxidize the
      NH(3)-N, was evaluated. The performance of the EGSB reactor was monitored for 12
      months in a pilot-scale plant. Iron shavings were added to the EGSB reactor on
      the sixtieth day to improve the removal efficiency of the chemical oxygen demand
      (COD), suspended solids (SS) and total phosphorus (TP). After the iron shavings
      were added, the effluent COD, SS and TP decreased from 104 to 46 mg L(-1), 21 to
      8.6 mg L(-1) and 3.62 to 1.36 mg L(-1), respectively. Moreover, in the EC
      reactor, which was equipped with IrO(2)/Ti anodes, the NH(3)-N and total nitrogen
      (TN) concentrations decreased from 25 to 12 mg L(-1) and 29 to 15 mg L(-1),
      respectively. The NH(3)-N was directly oxidized to N(2), resulting in no
      secondary pollution. The results demonstrated the possibility of removing carbon
      and nutrients in a SITS with high efficiency. The system runs efficiently and
      with a flexible operation, making it suitable for low-strength wastewater. The
      results and parameters presented here can provide references for the practical
      project.

PMID- 21741766
TI  - Two-scale evaluation of remediation technologies for a contaminated site by
      applying economic input-output life cycle assessment: risk-cost, risk-energy
      consumption and risk-CO2 emission.
AB  - A two-scale evaluation concept of remediation technologies for a contaminated
      site was expanded by introducing life cycle costing (LCC) and economic input
      output life cycle assessment (EIO-LCA). The expanded evaluation index, the rescue
      number for soil (RN(SOIL)) with LCC and EIO-LCA, comprises two scales, such as
      risk-cost, risk-energy consumption or risk-CO(2) emission of a remediation. The
      effectiveness of RN(SOIL) with LCC and EIO-LCA was examined in a typical
      contamination and remediation scenario in which dieldrin contaminated an
      agricultural field. Remediation was simulated using four technologies: disposal,
      high temperature thermal desorption, biopile and landfarming. Energy consumption
      and CO(2) emission were determined from a life cycle inventory analysis using
      monetary-based intensity based on an input-output table. The values of RN(SOIL)
      based on risk-cost, risk-energy consumption and risk-CO(2) emission were
      calculated, and then rankings of the candidates were compiled according to
      RN(SOIL) values. A comparison between three rankings showed the different ranking
      orders. The existence of differences in ranking order indicates that the scales
      would not have reciprocal compatibility for two-scale evaluation and that each
      scale should be used independently. The RN(SOIL) with LCA will be helpful in
      selecting a technology, provided an appropriate scale is determined.

PMID- 21741767
TI  - Simulation and quantification of the natural decay of a typical endocrine
      disrupting chemical Atrazine in an aquatic system.
AB  - The degradation of Atrazine (ATZ) in an outdoor environment was investigated by
      varying the ATZ concentration and pH levels and then cross-checked with
      temperature and sunlight information. The overall decay rate constant of ATZ in
      outdoor is slower in neutral pH and faster at extreme pH levels, while parallel
      tests show that higher ATZ concentration leads to slower decay rate constant. Two
      abiotic mechanisms including direct photolysis and hydrolysis were identified and
      studied in the laboratory as a comparison. Hydrolysis was found to be a slow
      process but it is a continuous process, which is critical as the sunlight
      intensity is weak. Effect of temperature on the hydrolysis was also studied. A
      model incorporating ATZ decay rate constants, pH levels and temperatures was
      proposed. Photolysis, though, is a non-continuous process in the environment. It
      is a fast and dominant process, which contributes 82-45% (depending on pH levels)
      of overall ATZ decay at outdoor. In natural environment, humic acid can act as
      photosensitizer and enhance photolysis of ATZ at low concentration (<10mg/L);
      while at high concentration of humic acid, retardation of ATZ decay was observed
      likely due to the scavenging of radicals and light attenuation.

PMID- 21741768
TI  - Comparing patients' and clinician-researchers' outcome choice for psychological
      treatment of chronic pain.
AB  - In pain treatment, outcomes are generally defined by researchers and clinicians,
      predominantly using patient self-report. A large-scale survey of people with
      chronic pain found a more extensive range of treatment outcomes rated important
      (Turk et al., "Identifying important outcome domains for chronic pain clinical
      trials: an IMMPACT survey of people with pain." PAIN 2008;137:276-85) than are
      conventionally used (Turk et al., "Core outcome domains for chronic pain clinical
      trials: IMMPACT recommendations." PAIN 2003;106:337-45). We compared outcomes
      from 60 randomised, controlled trials of cognitive and/or behavioural treatment
      for persistent pain with the 19 domains rated as most important in the survey.
      Only 2 outcomes, physical activities and emotional well-being, were assigned
      comparable importance by survey respondents and clinician-researchers. Five of
      the 19 outcomes important to survey respondents were not measured at all, and 8
      rarely. There was a positive, although modest, correlation between the
      methodological quality of trials and their coverage of survey respondents'
      outcomes. We lack measures in many areas of outcome valued by people with chronic
      pain, and we need to extend routine measurement of trial outcomes.

PMID- 21741769
TI  - The DSM Guided Cannabis Screen (DSM-G-CS): description, reliability, factor
      structure and empirical scoring with a clinical sample.
AB  - Clinicians need cannabis-specific diagnostic screens compatible with DSM-IV-TR
      and proposed DSM-5. A clinical sample (n=174) completed the DSM-Guided-Cannabis
      Screen (DSM-G-CS) 21 and 11 criteria versions and three drug comparison measures.
      DSM-G-CS descriptive statistics, reliabilities, three factor analyses, and eight
      ROC and discriminant analyses evaluated construct validity and empirical scoring.
      DSM-G-CS reliabilities are .88 (21-items) and .85 (11-criteria). Factor analyses
      (FA) with varimax rotation derived six and three factors explaining 62% to 60% of
      variances for the DSM-G-CS 21 and 11 respectively, with >=.400 loadings
      supporting retention of all items. Cannabis withdrawal subscale reliability .952
      (10-items) and FA supported one factor composite item. ROC and discriminant
      analyses supports DSM-G-CS 1.5 to 2.5 scoring cutoffs as empirically sound, based
      upon sensitivity-specificity maximums, accuracy probabilities, confidence levels
      and correctly classified percentages, optimal with Marijuana Screening Inventory
      (MSI) comparisons. Results support DSM-G-CS construct validity, empirical scoring
      and compatibility with DSM-IV-TR cannabis abuse or dependence and proposed DSM-5
      cannabis use disorder diagnostic models. Clinically, DSM-G-CS scores of two to
      three (or more) suggest probable cannabis-use disorder, deserving assessment to
      determine diagnostic accuracy.

PMID- 21741770
TI  - The changing scene in Hashimoto's disease: a review.
AB  - The review briefly describes the evolution of hypotheses about cronic
      thyroiditis, the escape of colloid hypothesis, basement membrane destruction, the
      auto-immune theory and the role of disregulatory genes.

PMID- 21741771
TI  - Stressor-induced NMDAR dysfunction as a unifying hypothesis for the aetiology,
      pathogenesis and comorbidity of clinical depression.
AB  - Typically the monoamine system has been the central focus of neurobiological
      research into depression and represents the major target of modern antidepressant
      medications; although the extent to which monoamines such as serotonin play a
      role in the pathogenesis of depression is still not clear. Recent research
      advancements have expanded the neurotransmitter-level focus of mood disorders to
      incorporate intracellular pathways and regional brain circuitry. As such the
      importance of other systems has emerged including those related to neuroplastic
      signal transduction and gene transcription cascades within cortico-limbic
      circuits. Indeed mounting evidence suggests interaction with these pathways is
      required for the chronic therapeutic effect of current clinical antidepressants.
      Dysfunction of the glutamatergic system has also emerged as a major pathological
      feature in depression, and glutamatergic agents have demonstrated rapid and
      robust antidepressant activity in humans. In particular, the glutamate receptors
      (AMPAR, NMDAR & mGluR) are intrinsically connected to neuronal efficiency and
      inefficiency cascades, so their dysfunction may account for alterations to
      multiple signal transduction pathways in depression. This article presents
      concepts supporting a NMDA hypothesis of depression, whereby the pathogenesis of
      depression may arise from stressors inducing excessive NMDAR activity which acts
      heterogeneously at both cellular and regional levels to disrupt normal
      neurobiological function and induce the depressive phenotype. In this hypothesis
      multiple psychological and environmental stressors are united in their capacity
      to potentiate excessive tonic and phasic NMDAR activation on neurons and glia.
      Such NMDAR dysfunction may lead to: disruption of glia processes and tripartite
      signalling; potentiation of extrasynaptic inefficiency/LTD pathways in some
      regions (e.g. prefrontal cortex & hippocampus); potentiation of synaptic
      efficiency/LTP pathways in other regions (e.g. amygdala); and regional disruption
      of cortico-limbic circuits and dopaminergic reward pathways (e.g. nucleus
      accumbens). This model unites depression with a variety of stressors including
      glucocorticoids, inflammation, oxidative stress, magnesium deficiency,
      hyperhomocysteinemia, and bio-energetic dysfunction; and also helps explain
      comorbidity with other neurological and affective disorders. In particular, a
      neurometabolic contribution to the aetiology of depressive as well as other
      neurological and affective disorders is explored.

PMID- 21741772
TI  - Treatment of boutonniere finger deformity in rheumatoid arthritis.
AB  - Boutonniere finger deformities occur frequently in patients with rheumatoid
      arthritis. The deformity consists of flexion of the proximal interphalangeal
      joint and hyperextension of the distal interphalangeal joint. Treatment decisions
      are based on the degree of joint deformity, joint motion, passive joint
      correctability, and the status of the articular surface. Treatment options can
      then be based on the classification of the deformity; options consist of
      corrective splinting, injections, synovectomy, terminal tenotomy, extensor
      reconstruction, or salvage surgery (arthrodesis or arthroplasty).

PMID- 21741773
TI  - Intraneural nodular fasciitis of the median nerve: case report and literature
      review.
AB  - Nodular fasciitis, a benign soft tissue tumor, occurs most frequently in the
      forearm and is generally divided into subcutaneous, intramuscular, and fascial
      types. Intraneural nodular fasciitis has been reported in only 5 patients
      previously. We present the case of a 79-year-old woman with nodular fasciitis
      within the median nerve at the proximal forearm. Carpal tunnel syndrome was
      suspected at the initial visit, but high median nerve palsy and a mass at the
      proximal forearm were found a few months later. Subtotal resection of the tumor
      within the median nerve was performed and histological diagnosis indicated
      nodular fasciitis. There was no evidence of recurrence at follow-up 1 year and 3
      months after surgery. Motor weakness had resolved but sensation was compromised.

PMID- 21741774
TI  - Decency, honor, integrity, and the law.
AB  - In its guidelines for hand care professionals, the American Society for Surgery
      of the Hand has set the following criteria as guidelines for the ethical hand
      surgeon in the 21st century: decency, honor, and integrity. This article reviews
      these criteria in detail, relates how they apply in practice, and describes how
      they interact with state and federal law in both legislative and judicial
      aspects. Matters pertaining to informed consent, privacy issues, patient
      autonomy, shared decision making, and conflict of interest are described, and
      recent developments in this area are examined. Are hand surgeons ready for an
      enforceable system of ethics to be handed down by the ASSH or by the government?

PMID- 21741775
TI  - Upper extremity surgery after lymph node dissection.

PMID- 21741776
TI  - Isolated displaced olecranon fracture.

PMID- 21741778
TI  - Chronic thumb metacarpophalangeal joint ulnar collateral ligament insufficiency.

PMID- 21741779
TI  - Nondisplaced fractures of the proximal carpal row: case report.
AB  - We present a 24-year-old woman who sustained isolated nondisplaced fractures of
      the proximal carpal row after a low-energy injury. The radiographic features are
      most consistent with the recently described translunate arc injury and appear to
      be a transitional injury between an inferior arc injury as well as the greater
      and lesser arc injuries. The injury was successfully treated with below-elbow
      thumb-spica cast immobilization for 10 weeks.

PMID- 21741780
TI  - [Medical abortion from 12 through 14 weeks' gestation: a retrospective study with
      126 patients].
AB  - OBJECTIVE: To assess the efficacy of medical abortion performed according to a
      single protocol from 12 through 14 weeks. STUDY DESIGN: Retrospective
      observational study of medical abortions from 12 through 14 weeks performed from
      January 2007 through March 2009. The protocol combined 600 mg de mifepristone
      orally, followed 48 h later by 400 MUg of misoprostol, administered orally, and
      repeated after 3h, four times a day (during two days), if patient did not begin
      to abort. Outcome measures were the abortion rate, the rate of complication, the
      rate of manual uterine revision or vacuum aspiration, the time of expulsion and
      the misoprostol dose. RESULTS: The study included 126 medical abortions. The
      abortion rate was 98% and the secondary manual revision or vacuum aspiration rate
      was 41%. The mean time to expulsion was 10.4 (+/-8.8)h, and the mean misoprostol
      dose 1040 (+/-420) MUg. Higher parity was significantly correlated with shorter
      time to expulsion (P=0.02). CONCLUSION: Medical abortion was consistently
      effective from 12 through 14 weeks but with high rate of secondary manual
      revision or vacuum aspiration.

PMID- 21741781
TI  - The association between outpatient buprenorphine detoxification duration and
      clinical treatment outcomes: a review.
AB  - BACKGROUND: The association between buprenorphine taper duration and treatment
      outcomes is not well understood. This review evaluated whether duration of
      outpatient buprenorphine taper is significantly associated with treatment
      outcomes. METHODS: Studies that were published in peer-reviewed journals,
      administered buprenorphine as an outpatient taper to opioid-dependent
      participants, and provided data on at least one of three primary treatment
      outcome measures (opioid abstinence, retention, peak withdrawal severity) were
      reviewed. Primary treatment outcomes were evaluated as a function of taper
      duration using hierarchical linear regressions with pre-taper maintenance
      duration as a cofactor. RESULTS: Twenty-eight studies were reviewed. Taper
      duration significantly predicted percent of opioid-negative samples provided
      during treatment, however pre-taper maintenance period predicted percent
      participants abstinent on the final day of treatment. High rates of relapse were
      reported. No significant association between taper duration and retention in
      treatment or peak withdrawal severity was observed. CONCLUSION: The data reviewed
      here suggest taper duration is associated with opioid abstinence achieved during
      detoxification but not with other markers of treatment outcome. The reviewed
      studies varied widely on several parameters (e.g., frequency of urinalysis
      testing, provision of ancillary medications) that may influence treatment outcome
      and thus could have interfered with the ability to identify relationships between
      taper duration and outcomes. Future studies evaluating opioid detoxification
      should utilize rigorous experimental methods and report a wider range of outcome
      measures in order to help advance our understanding of the association between
      taper duration and treatment outcomes.

PMID- 21741782
TI  - Microarray and cytokine analyses of field cases of pigs with diarrhoea.
AB  - This field study explored the cytokine expression in intestinal tissue and serum
      from 19 diarrhoeic and 9 healthy pigs in herds with a long-time history of
      Lawsonia intracellularis-infection. The disease, proliferative enteropathy (PE),
      is associated with diarrhoea and poor performance in growers and haemorrhagic
      diarrhoea and sudden death in finisher pigs, but the immunopathology is poorly
      understood. Histopathology, demonstration of L. intracellularis and porcine
      circovirus type 2 (PCV2) in intestinal tissue by PCR, and detection of serum
      antibodies to L. intracellularis, were performed. The presence of IL-1beta, IL-6,
      IL-10, IFN-alpha, IFN-gamma, TNF-alpha and TGF-beta in sera was determined by
      immunoassays, and intestinal mRNA expression of these cytokines plus IL-12p40 was
      determined by qPCR. Intestinal specimens from pigs with intestinal adenomatosis
      (n=2), proliferative haemorrhagic enteropathy or swine dysentery (n=2), and
      controls (n=2) were analysed by a genome wide porcine microarray. The clinical
      signs of PE were not always supported by the subsequent analyses, and the
      presence of PCV2 may have contributed to an increased mRNA expression for IFN
      gamma in intestinal specimens from some pigs. The limited gene expression in the
      microarray analyses and the limited expression of cytokines in both sera and
      intestines, indicate that the immune response is poorly activated in the initial
      course of an infection with L. intracellularis. However, the gene encoding for
      insulin-like growth factor binding protein 3 (IGFBP-3) was up-regulated in two
      pigs with prominent mucosal proliferation.

PMID- 21741783
TI  - Induction/synchronization of oestrus and ovulation in dairy goats with different
      short term treatments and fixed time intrauterine or exocervical insemination
      system.
AB  - Two experiments were carried out on Ionica dairy goats in order to test the
      efficiency of: (1) short term-5-day combined progestogen-PGF2alpha-GnRH
      treatments on induction/synchronization of oestrus and fertility after natural
      mating in lactating goats and during the transition period (Experiment 1); (2)
      short term-9-day FGA-PGF2alpha-eCG treatments on synchronizing oestrus and
      ovulation (Experiment 2.1) and artificial insemination (AI) fixed time system in
      synchronized does (Experiment 2.2), during the breeding season. In Experiment 1,
      four treatment groups (N=24) were considered: (1) FPe-11d - control, FGA
      intravaginal sponges (11 days)+PGF2alpha (9th d)+eCG (11th d); (2) FPe-5d, FGA (5
      days)+PGF2alpha (5th d)+eCG (5th d); (3) PFe-5d, PGF2alpha (D0)+FGA (5 days)+eCG
      (5th d); (4) GPe-5d, GnRH (D0)+PGF2alpha (5th d)+eCG (5th d). Goats were checked
      for oestrus and naturally mated. The occurrence of oestrus was 75.0, 78.3, 86.4,
      and 58.3% for groups 1-4, respectively, with significant differences (P<0.05)
      between groups 3 and 4. Interval to oestrus was earlier (P<0.05) in GPE-5d than
      in FPe-11d control group. There were no differences between the groups (P>0.05)
      in fertility or in prolificacy. In Experiment 2.1, 22 goats were subdivided into
      two treatment groups (N=11): (T1) FPe-11d (control), FGA (11 days)+PGF2alpha (9th
      d)+eCG (11th d); (T2) FPe-9d, FGA (9 days)+PGF2alpha (7th d)+eCG (9th d). Oestrus
      and ovulation times were monitored every 4h; ovulation rate was also determined.
      The induction of oestrus ranged from 91 to 100% and all goats ovulated. Intervals
      to oestrus, from the onset of oestrus to ovulation, from sponge removal to
      ovulation, and ovulation rates were 28.2+/-4.9 and 26.0+/-4.0h, 25.3+/-9.2 and
      28.9+/-7.4h, 53.5+/-7.6 and 54.9+/-7.1h, 3.7+/-1.6 and 2.4+/-1.4 corpora lutea
      (P<0.05) for T1 and T2, respectively. In T2 a great abnormal ovulatory response
      was observed. In Experiment 2.2, 48 goats were synchronized with FPe-9d treatment
      and subjected to AI, performed 50h after s.r. with frozen semen, and subdivided
      into 2 AI system groups (N=24): T3, exocervical AI (100*10(6)Spz/doe); T4,
      intrauterine AI (20*10(6)Spz/doe). Fertility rate was higher (P<0.05) in T4. It
      seems that short term-5-day combined progestogen-PGF2alpha-GnRH-eCG treatments
      need to be investigated for AI fixed time.

PMID- 21741784
TI  - The importance of carcass volatiles as attractants for the hide beetle Dermestes
      maculatus (De Geer).
AB  - A decaying cadaver emits volatile organic compounds that are used by necrophilous
      and necrophagous insects in order to find their brood substrate. Although
      volatile organic compounds (VOCs) that are released by carcasses have been
      identified, little is known about the specific compounds that are used by these
      insects while searching for a brood substrate. Therefore, we have investigated
      the chemical ecology involved in the attraction of the necrophagous hide beetle
      Dermestes maculatus, which feeds as an adult and larva upon decomposing
      carcasses. Our aims have been to identify the responsible compounds in the odours
      of the carcass that are important for the attraction of the beetles. Furthermore,
      we have studied sex- and age-related differences in beetle attraction and tested
      whether the hide beetle can distinguish between various stages of decomposition
      by means of the emitted odours. Headspace collection of volatiles released from
      piglet carcasses (bloated stage, post-bloating stage, advanced decay and dry
      remains), coupled gas chromatography-mass spectrometry (GC-MS), gas
      chromatography with electroantennographic detection (GC-EAD) and bioassays were
      conducted to identify the volatiles responsible for the attraction of the
      beetles. Freshly emerged male beetles were attracted by the odour of piglets in
      the post-bloating stage (9 days after death; T(mean) = 27  degrees C) and the EAD
      active compound benzyl butyrate. Statistical analysis revealed a higher relative
      proportion of benzyl butyrate in the odour bouquet of the post-bloating stage in
      comparison with the other stages. We therefore conclude that this compound plays
      an important role in the attraction of hide beetles to carcass odour. This
      underlines the potential use of D. maculatus for the estimation of the post
      mortem interval. The decomposition stage at which the female beetles are
      attracted to the odour of a cadaver remains unknown, as does the nature of this
      attraction. Pheromones (sexual or aggregation pheromones) might play an essential
      role correlated with their attraction to carrion and consequently with their
      attraction to the substrate for mating and ovipositioning.

PMID- 21741785
TI  - Comparison of findings of spontaneous splenorenal shunt in color Doppler
      sonography with multislice CT scan (64 slices) in liver transplant candidates.
AB  - BACKGROUND: Liver transplantation is the only definite treatment for end stage
      liver disease and it has high costs for the medical system so decreasing its
      complication and increasing its effectiveness is crucial. One of the factors that
      affect liver transplantation is the presence of spontaneous splenorenal shunt.
      Its diagnosis is mainly overlooked in pre-liver transplant patients. Main
      modality for its diagnosis is multislice CT scan however this is more expensive
      than sonography. Also, it exposes the patients to ionizing radiation. Considering
      the advantages of color Doppler ultrasound, studies to determine the sensitivity
      and specificity for detection of spontaneous splenorenal shunt is essential.
      MATERIALS AND METHODS: In our study 70 cirrhotic patients who were referred by
      liver transplant surgeons for evaluation of abdomen by CT and sonograhy were
      assessed for presence of spontaneous splenorenal shunt, left adrenal varix and
      left renal vein diameter and velocity and sensitivity and specificity of both
      modalities were checked. Patients in whom left renal vein could not evaluated by
      sonography and patients with splenectomy and nutcracker syndrome were excluded.
      RESULTS: In the point of 10 mm diameter of left renal vein in CT scan there was
      78.6% sensitivity and 67.9% specificity for the presence of spontaneous
      splenorenal shunt. Left adrenal varix in CT had sensitivity of 71.4%, specificity
      of 100%, and positive predictive value of 100% and negative predictive value of
      70% and varix below spleen in CT had sensitivity of 54.8%, specificity of 96.4%,
      and positive predictive value of 95.8% and negative predictive value of 58.7% for
      the presence of spontaneous splenorenal shunt. In the point of 8 mm diameter of
      left renal vein in sonography there was 66.7% sensitivity and 85.7% specificity
      for the presence of spontaneous splenorenal shunt. For the velocity of more than
      35 cm/s of left renal vein in sonography there was 61.9% sensitivity and 82.1%
      specificity for the presence of spontaneous splenorenal shunt. Left adrenal varix
      in sonography had sensitivity of 45.2%, specificity of 96.4%, positive predictive
      value of 95% and negative predictive value of 54% for the presence of spontaneous
      splenorenal shunt. CONCLUSION: There was moderate agreement between CT scan and
      sonography for detection of spontaneous splenorenal shunt. CT scan is choice for
      detection of SSRS but sonography is somehow useful. It means that if sonograhy is
      positive it is sufficient, if negative, then CT should be performed. This is due
      to low sensitivity of sonography.

PMID- 21741786
TI  - Successful extracorporeal membrane oxygenation treatment for pheochromocytoma
      induced acute cardiac failure.
AB  - The aim of this study is to report the case of a catecholamine-induced
      cardiogenic shock bridged to curative adrenalectomy using extracorporeal membrane
      oxygenation (ECMO) and medical management. A 37-year-old woman presented an acute
      cardiogenic shock due to a left-sided pheochromocytoma. Echocardiography revealed
      a severe global hypokinesia with a left ventricular ejection fraction of 15%.
      Despite maximal ionotropic support, adequate perfusion could not be achieved; and
      ECMO was used to bridge the patient during medical management with calcium
      channel blockers. The left ventricular ejection fraction improved to 65%, and
      ECMO was discontinued after 11 days. An open left adrenalectomy was performed 10
      days after ECMO. At 1-year follow-up, the patient is in good health with normal
      cardiac function. Pheochromocytomas can present with dramatic cardiovascular
      collapse. With timely diagnosis and medical therapy, followed by surgical
      resection, the cardiovascular effects can be reversed; and the condition, cured.
      Young patients with catecholamine-induced cardiac failure refractory to medical
      therapy are ideal candidates for short-term ECMO support, as the underlying cause
      is imminently reversible.

PMID- 21741787
TI  - Medication prescribing errors in the prehospital setting and in the ED.
AB  - BACKGROUND: Medication errors are a common cause of iatrogenic adverse drug
      events. The incidence and nature of medication errors during prehospital
      treatment have not been fully described. OBJECTIVES: The objectives of this study
      are to describe the incidence and characteristics of medication errors in adults
      during prehospital emergency treatment and in the emergency department (ED) and
      to identify risk factors for medication errors in those settings. METHODS: This
      is a retrospective study of adult patients transferred by emergency medical
      services to the ED of a university-affiliated hospital in Israel. The drugs
      administered in the mobile intensive care unit and in the ED were reviewed by 2
      reviewers, who independently decided whether an error had occurred. The primary
      outcome was the number of drug errors per patient. Secondary outcomes were the
      type and severity of the errors and variables associated with increased incidence
      of drug errors. RESULTS: During the study period, 1837 patients were brought to
      the ED by mobile intensive care unit vehicles. Five hundred thirty-six patient
      charts (29%) were randomly selected for review; 65 charts (12.12%) could not be
      found; thus, 471 charts were reviewed. In the emergency vehicle, 188 patients
      (45.63%) received medications; of those, 12.76% (24 patients) were subject to a
      medication error. The number of drugs administered and long evacuation times were
      associated with higher risk for an error (P<.01 and P=.011, respectively). The
      presence of a physician in the emergency vehicle did not alter the risk of an
      error (P=.95). In the ED, 332 patients (72.6%) received medications. Of those,
      medication errors occurred in 120 patients (36.1%). The more medications
      administered, the higher the risk of error (P<.01). Less errors occurred in
      trauma patients (P=.041). CONCLUSION: More medication errors occur in the ED than
      in the emergency vehicles. Patients treated with multiple medications are more
      prone to medication errors.

PMID- 21741788
TI  - Hybrid management of ruptured isolated superior mesenteric artery dissecting
      aneurysm.
AB  - A 70-year-old woman, with history of asymptomatic isolated superior mesenteric
      artery (SMA) dissection was admitted for acute abdominal pain. Computed
      tomography showed ruptured isolated SMA dissection. Endovascular treatment was
      chosen over surgical repair because of prior abdominal surgeries. Because an
      angulated SMA trunk and compressed true lumen by the dilated false lumen
      prevented the insertion of a guidewire into the SMA via the transfemoral artery,
      transmesenteric approach under laparotomy was selected. After creating a pull
      through condition from the SMA to the left brachial artery, a successful stent
      graft placement with adequate hemostasis was achieved. The aneurysm shrunk
      remarkably, with no complication at follow-up.

PMID- 21741789
TI  - Contrast-induced nephropathy.
AB  - Contrast-induced nephropathy (CIN) has been extensively studied since the 1950s
      due, in part, to its devastating adverse events. The intellectual push for
      additional investigation into pathogenesis and prevention has heightened in
      recent years due to increased utilization of contrast enhanced imaging studies.
      Lack of a universal CIN definition and varied glomerular filtration rate markers
      have resulted in a varied reported incidence. Risk assessment and risk reduction
      strategies have evolved over the past several years. Current evidence supports
      volume supplementation before the administration of intravascular contrast to
      reduce the hazard of CIN. Other strategies to reduce the risk of CIN, including
      low osmolar contrast media, N-acetylcysteine, and intrarenal fenoldopam therapy,
      have variable levels of evidence, and further randomized trials are necessary.

PMID- 21741790
TI  - Primary aortoenteric fistula following endovascular aortic repair due to type II
      endoleak.
AB  - An 84-year-old female was lost to follow-up after endovascular aneurysm repair at
      another hospital with known type II endoleak. She later presented with presyncope
      and hematemesis. A referral center esophagogastroduodenoscopy showed possible
      duodenal diverticulum. She had recurrent symptoms and repeat computed tomography
      scan showed air within the aortic sac. At our center, she underwent stent graft
      explantation and axillofemoral reconstruction for a primary aortoenteric fistula.
      She was discharged and is doing well 5 months postoperatively. A high degree of
      suspicion for aortoenteric fistula is imperative in any patient with upper
      gastrointestinal hemorrhage after open or endovascular abdominal aortic aneurysm
      repair.

PMID- 21741791
TI  - Anticoagulation monitoring by an anticoagulation service is more cost-effective
      than routine physician care.
AB  - BACKGROUND: Vitamin K antagonists (VKAs) are the mainstay of long-term
      anticoagulation but require careful monitoring for effectiveness and safety.
      Physicians manage anticoagulation for most patients, although anticoagulation
      services are becoming increasingly popular. A new anticoagulation service (AS)
      run by nurses and overseen by a physician was established and its effectiveness
      vs usual physician care was independently assessed using costs of emergency
      department (ED) visits and hospitalizations resulting from failure or
      complication of anticoagulation. We report the results of this independent
      analysis of anticoagulation monitoring of patients treated with VKAs. METHODS:
      The AS-treated patients received VKAs according to a written protocol, whereas
      physician monitoring was performed according to individual practice. An
      independent analysis of ED visits and hospitalizations due to complications of
      anticoagulation in patients receiving long-term VKAs between July 1, 2008, and
      December 31, 2008, was performed. The average cost of ED visits and
      hospitalizations was calculated for each patient cohort. The expense of each was
      amortized for a 12-month period to determine the annual cost of anticoagulation
      morbidity per 100 patients treated. RESULTS: Long-term VKAs were used to treat
      2397 patients. Physicians managed 2266 patients (95%; group I) and the AS
      monitored 131 patients (5%; group II). In group I, 247 patients (10.9%) visited
      the ED, with an average cost of $288 per visit; the ED cost per patient treated
      was $31. In group II, two patients (1.5%) visited the ED, with an average cost of
      $139 per patient. The ED cost per patient treated was $2, leading to annual
      savings of $5800 per 100 patients (P = .0006). Complications of anticoagulation
      required hospitalization in 289 group I patients (12.8%), with an average cost of
      $15,125 per hospitalization and $1929 per patient treated and in three group II
      patients (2.3%), with an average cost of $17,794 per hospitalization and an
      average cost of $401 per patient treated. When the savings from ED visits and
      hospitalizations were combined, AS-managed anticoagulation led to annual savings
      of $305,600 (P = .0004). Subtracting the cost of staff services resulted in a
      yearly net savings of $241,400 per 100 patients (P <= .0001) managed by the AS.
      CONCLUSIONS: Management of long-term VKA therapy by an AS using established
      protocols appears to reduce anticoagulation morbidity and results in significant
      cost savings by reducing the number of ED visits and hospitalizations.

PMID- 21741792
TI  - Thoracic aorta aneurysm repair using the right axillary approach.
AB  - We present a 66-year-old man with a 5.7-cm saccular descending thoracic aortic
      aneurysm and a smaller 4.6-cm aneurysm just proximal to the celiac artery. The
      patient was judged to be too risky for open surgical repair because of poor
      anatomy and health. Previous stenting of the iliac arteries for a kinked
      aortoiliac open graft precluded conventional endovascular aneurysm repair. The
      descending thoracic aorta was successfully repaired using endovascular methods
      with a standard Talent (Medtronic, Los Angeles, Calif) thoracic proximal main
      stent graft, which was reverse-loaded onto the delivery device and delivered
      antegrade through the right axillary artery.

PMID- 21741793
TI  - Technical and clinical success after endovascular therapy for chronic type B
      aortic dissections.
AB  - OBJECTIVE: To analyze early technical success and late clinical success after
      endovascular entry sealing for chronic type B dissection with special emphasis on
      reintervention, false lumen thrombosis, and aortic remodeling. METHODS:
      Retrospective analysis of a prospective database. From September 1999 to January
      2011, 19 patients with chronic type B dissections were treated by endovascular
      entry sealing. Median age was 60 years. Median time between onset of acute
      dissection and surgical intervention was 36 (1 to 60) months. Median follow-up
      was 13 months (1 to 124). RESULTS: The endografts used were: Medtronic Captivia
      (5), Medtronic Valiant (5), Gore TAG (6), Gore C-TAG (2), and Cook Zenith (1). In
      four patients, revascularization of the left subclavian artery was performed
      prior to entry sealing. Primary technical success rate (entry sealing, absence of
      type I leak) was 18/19 (94.7%). In-hospital mortality was 0%. Spinal cord injury
      with persistent paraplegia occurred in 1/19 (5.2%) patients. After a maximal
      follow-up of 124 months, reinterventions in 9/19 (47.3%) were necessary:
      distal/proximal extension of stent graft (8), replacement of the aortic arch due
      to retrograde dissection (1), and open infrarenal aneurysm repair (1). During
      follow-up, none of the patients died due to stent-related complications.
      CONCLUSION: Endovascular treatment (EVT) in chronic type B dissections has a high
      technical success rate and low mortality/morbidity. However reintervention rates
      are not negligible which might reduce the clinical success of EVT. Future
      investigations should aim at identifying patients who benefit from EVT at better
      defining the timing of EVT and at determining if entry sealing alone is
      sufficient.

PMID- 21741794
TI  - Comparative proteomics reveals a systemic vulnerability in the vasculature of
      patients with abdominal aortic aneurysms.
AB  - INTRODUCTION: Abdominal aortic aneurysms (AAA) are associated with inflammation,
      apoptosis, and matrix degradation. AAA tissue represents the end stage of
      disease, limiting its utility in identification of factors culpable for
      initiation of aneurysm development. Recent evidence suggests that AAAs are a
      local representation of a systemic disease of the vasculature. Morphologic and
      molecular changes, comparable to those found in the aneurysm wall, have been
      demonstrated in veins from patients with AAAs. Changes in the vascular tissue
      proteome of patients with AAAs were investigated, using inferior mesenteric vein
      (IMV), to gain insight into early molecular changes contributing to AAA
      development. METHODS: IMV was harvested from 16 patients with AAA and 16 matched
      controls. Whole IMV lysates were subjected to 2-D difference in gel
      electrophoresis (2D-DIGE) with quantitative densitometry. Protein spots
      differentially expressed in AAA were identified using mass spectrometry.
      Differential protein expression was validated by Western blotting and localized
      to cell type by immunohistochemistry (IHC). RESULTS: Decreased levels of
      prohibitin (AAA, 2.00 +/- 1.37; controls, 3.81 +/- 1.39; 1.9-fold change; P =
      .02) AAA (7.33 +/- 3.9; controls, 14.5 +/- 5.6; 2-fold change; P = .001), along
      with relative increases in a cleaved fragment of vimentin (AAA, 12.9 +/- 9;
      controls, 6.9 +/- 4.7; 2-fold change; P = .11) were identified in AAA patients.
      All proteins were localized to the vascular smooth muscle cells. CONCLUSIONS:
      Proteins important in combating the injurious effects of oxidative stress and
      modulating the response to inflammation appear reduced in the vasculature of
      patients with AAA. These changes may represent early events in AAA formation.
      Enhancing expression of these proteins might offer a novel therapeutic avenue to
      inhibit AAA development.

PMID- 21741795
TI  - Painless transient paraparesis as the solitary manifestation of aortic
      dissection.
AB  - We present a 62-year-old man with acute and temporary paraparesis of the lower
      extremities as the solitary symptom of an anterior spinal artery syndrome caused
      by a type B aortic dissection. Ischemia of the spinal cord was confirmed by
      magnetic resonance imaging. Neurologic symptoms resolved completely within 6
      hours and conservative treatment was successful up to 8 months follow-up. Our
      report illustrates that painless, transient neurologic deficit can be the only
      presenting symptom of acute aortic dissection and that aortic dissection should
      be part of the differential diagnosis of acute paraparesis.

PMID- 21741796
TI  - Validation of a new technique to determine midbundle femoral tunnel position in
      anterior cruciate ligament reconstruction using 3-dimensional computed tomography
      analysis.
AB  - PURPOSE: The purpose of this study was to investigate and report on a new
      intraoperative measuring technique to place the anterior cruciate ligament (ACL)
      femoral tunnel in the center of the native ACL femoral insertion site. METHODS:
      We investigated a novel measuring technique based on identifying the proximal
      border of the articular cartilage and using a specific ruler parallel to the
      femoral axis to locate the origin of the ACL. The accuracy of this technique was
      validated by measuring tunnel position on postoperative 3-dimensional computed
      tomography scans. Bony tunnels created by the ruler technique were compared with
      tunnels drilled by a traditional technique referenced from the back wall of the
      notch. RESULTS: Fifty ACL reconstructions were performed by the novel measuring
      technique, with placement of the femoral tunnel at the center of the femoral
      insertion. The mean position for the center of the femoral tunnel measured by the
      ruler technique was 0.9 mm from the theoretic optimal center position but was a
      very distinct 5 mm from the mean position in the traditional tunnels.
      CONCLUSIONS: The ruler technique produced femoral tunnels comparable to published
      radiographic criteria used for tunnel placement and is reproducible and accurate.
      We recommend placement of the femoral tunnel at the midpoint of the lateral
      femoral condyle when using the anatomic single-bundle technique. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 21741797
TI  - Pathways to change in one-session exposure with and without cognitive
      intervention: an exploratory study in spider phobia.
AB  - It is well established that exposure therapy is an effective treatment for
      anxiety disorders. It is less clear, however, which mechanisms are crucial in
      explaining its success. In previous studies, cognitive change has been identified
      as a mediating variable. Several theorists have argued that the addition of
      cognitive interventions will, therefore, result in enhanced treatment effects. We
      tested this hypothesis by examining cognitive mediation of treatment in a purely
      behavioral versus a cognitive-behavioral exposure format. Thirty-one spider
      phobics were randomly assigned to either behavioral exposure or to exposure as a
      test for maladaptive cognitions (i.e., behavioral experiments). Both treatment
      formats showed large treatment effects and strong cognitive mediation of these
      effects. This indicates that, even when cognitions are not explicitly targeted,
      exposure effects are cognitively mediated. This challenges the idea that
      cognitions have to be explicitly challenged to elicit cognitive change in
      exposure treatment.

PMID- 21741798
TI  - "It's a touchy subject": Latino adolescent sexual risk behaviors in the school
      context.
AB  - Adverse sexual health outcomes remain disproportionately high for Latino
      adolescents. To examine sexual risk behaviors in Latino adolescents, we conducted
      in-depth interviews with 18 Latino parents and 13 school staff members and
      carried out 1 year of fieldwork in the school and community. "It's a touchy
      subject [sex] here" exemplified the reluctance of addressing sexual risk
      behaviors. Community- and systems-level strategies are recommended.

PMID- 21741799
TI  - Impact of diabetes on muscle mass, muscle strength, and exercise tolerance in
      patients after coronary artery bypass grafting.
AB  - BACKGROUND: The impact of diabetes mellitus (DM) on muscle mass, muscle strength,
      and exercise tolerance in patients who had undergone coronary artery bypass
      grafting (CABG) has not been fully elucidated. METHODS: We enrolled 329
      consecutive patients who received cardiac rehabilitation (CR) after CABG (DM
      group, n=178; non-DM group, n=151) and measured lean body weight, mid-upper arm
      muscle area (MAMA), and handgrip power (HGP) at the beginning of CR. We also
      performed an isokinetic strength test of the knee extensor (Ext) and flexor
      (Flex) muscles and a cardiopulmonary exercise testing at the same time. RESULTS:
      No significant differences in risk factors, including age, gender, number of
      diseased vessels, or ejection fraction were observed between the 2 groups. The
      levels of Ext muscle strength, peak oxygen uptake, and anaerobic threshold were
      significantly lower in the DM group than in the non-DM group (all p<0.05). Both
      peak oxygen uptake and MAMA correlated with Ext and Flex muscle strength as well
      as HGP (all p<0.005). The MAMA, HGP, and Ext muscle strength were lower in
      patients who received insulin therapy than in those who did not. Interestingly,
      fasting glucose levels significantly and negatively correlated with Ext muscle
      strength. CONCLUSIONS: These data suggest that DM patients had a lower muscle
      strength and exercise tolerance than non-DM patients. Moreover, a high glucose
      level may affect these deteriorations in DM patients after CABG.

PMID- 21741800
TI  - Clinical study of the electrophysiological effects of ischemic post-conditioning
      in patients with acute myocardial infarctions.
AB  - BACKGROUND: Ischemic "pre"-conditioning has been shown to have antiarrhythmic
      effects. The aim of this study was to investigate whether ischemic "post"
      conditioning (post-CON) also has antiarrhythmic effects in ST-segment elevation
      myocardial infarction (STEMI) patients undergoing coronary angioplasty (PCI) as a
      clinical model of post-CON. METHODS AND RESULTS: A total of 61 patients suffering
      from an acute myocardial infarction (AMI) were included. The QT dispersion (QTd)
      was measured before each balloon inflation (BI) and after deflation (BD) during
      PCI. The hemodynamic parameters and electrocardiogram were also assessed during
      PCI. All data were analyzed using a logistic regression analysis. A total of 36
      of 61 STEMI patients could be analyzed according to the protocol. The QTd
      shortened significantly as the BI and BD were repeated (p<0.05). Prior to the
      PCI, frequent premature ventricular contractions (PVCs) were observed in 5
      patients, and the PVCs were remarkably suppressed or disappeared entirely as the
      BI and BD were repeated. Non-sustained ventricular tachycardia was observed prior
      to the PCI in 2 patients; this also disappeared as the BI and BD were repeated.
      Ventricular fibrillation (VF) occurred in 1 patient prior to PCI, necessitating D
      C cardioversion. After repeating the BI and BD during PCI, VF no longer recurred.
      CONCLUSIONS: In the majority of the AMI patients studied, post-CON exhibited
      significant antiarrhythmic effects as assessed by the change in the QTd. The
      ventricular dysarrhythmias were also suppressed during the PCI.

PMID- 21741801
TI  - Potent antimicrobial peptides with selectivity for Bacillus anthracis over human
      erythrocytes.
AB  - In this study, 39 antimicrobial peptides, most with documented low haemolytic
      activity and potent efficacy against Gram-negative and Gram-positive bacteria,
      were evaluated for their haemolytic activity against human red blood cells as
      well as their antimicrobial activity against Escherichia coli, Burkholderia
      thailandensis, Bacillus globigii and Bacillus anthracis. The majority of the
      peptides had a minimum inhibitory concentration (MIC) of <10 MUM against B.
      globigii. However, only eight of these (CaLL, Ci-MAM-A24, LLaMA, Ltc2a, OV-5,
      papillosin, smapspin and smapspin-G) had a MIC<10 MUM against B. anthracis. All
      except one (papillosin) were ineffective at 100 MUM against B. thailandensis and
      none had potent activity against E. coli. Potent activity against B. anthracis
      was associated with significant haemolytic activity, but the ratio of the
      concentration of peptide that caused 50% haemolysis to the concentration that
      inhibited growth of B. anthracis by 50% (the therapeutic index) varied from 0.8
      to 34.2. Two peptides (papillosin and Ltc2a) had a therapeutic index >30 and
      could be considered as candidates for further development for potential medical
      countermeasures against anthrax. Although B. globigii has often been used as a
      non-pathogenic simulant for B. anthracis, in this study it was found that the
      sensitivity of B. globigii to peptides was not a reliable predictor of the
      sensitivity of B. anthracis to the same peptides.

PMID- 21741802
TI  - Trimethoprim/sulfametrole: evaluation of the available clinical and
      pharmacokinetic/pharmacodynamic evidence.
AB  - Emergence of resistance to widely used trimethoprim/sulfamethoxazole (TMP/SMX) as
      well as common adverse events in human immunodeficiency virus (HIV)-infected
      patients casts interest on combinations of TMP with other sulfonamides.
      Sulfametrole (SMT) combined with TMP could provide a choice for difficult-to
      treat infections, particularly when administered intravenously. The objective of
      this review was to evaluate the available clinical and
      pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding TMP/SMT, particularly
      in comparison with TMP/SMX. We reviewed the available evidence retrieved from
      searches in PubMed/Scopus/Google Scholar and by bibliography hand-searching. In
      total, 46 eligible studies (most published before 1997) were identified, 7
      regarding intravenous (i.v.) TMP/SMT, 24 regarding oral TMP/SMT and 15 providing
      comparative data for TMP/SMT versus TMP/SMX. The antimicrobial activity of
      TMP/SMT was similar to TMP/SMX for Gram-positive isolates. A greater percentage
      of Escherichia coli and Proteus spp. isolates were susceptible to TMP/SMT
      compared with TMP/SMX. PK/PD data suggest a dosage adjustment of i.v. TMP/SMT in
      patients with seriously impaired renal function. Four randomised controlled
      trials and 16 non-comparative studies reported good effectiveness/safety outcomes
      for oral TMP/SMT in genital ulcers (mainly chancroid), respiratory tract
      infections and urinary tract infections (UTIs). Moreover, i.v. TMP/SMT was
      effective against Pneumocystis jiroveci infection in HIV-infected patients,
      severe pneumonia and UTIs. In one study, hypersensitivity reactions occurred in
      18/52 (34.6%) of HIV-infected patients; 2/52 (3.8%) developed psychosis.
      Gastrointestinal adverse events were mild and rare. Excipients in i.v. TMP/SMT
      formulations might be less toxic compared with i.v. TMP/SMX formulations,
      particularly for children. In conclusion, despite the scarcity of contemporary
      evidence, available data suggest that TMP/SMT could be an alternative treatment
      option to TMP/SMX, even in serious infections, when administered intravenously.

PMID- 21741803
TI  - Substance use and regional gray matter volume in individuals at high risk of
      psychosis.
AB  - Individuals with an at risk mental state (ARMS) are at greatly increased risk of
      developing a psychotic illness. Risk of transition to psychosis is associated
      with regionally reduced cortical gray matter volume. There has been considerable
      interest in the interaction between psychosis risk and substance use. In this
      study we investigate the relationship between alcohol, cannabis and nicotine use
      with gray matter volume in ARMS subjects and healthy volunteers. Twenty seven
      ARMS subjects and 27 healthy volunteers took part in the study. All subjects
      underwent volumetric MRI imaging. The relationship between regional gray matter
      volume and cannabis use, smoking, and alcohol use in controls and ARMS subjects
      was analysed using voxel-based morphometry. In any region where a significant
      relationship with drug was present, data were analysed to determine if there was
      any group difference in this relationship. Alcohol intake was inversely
      correlated with gray matter volume in cerebellum, cannabis intake was use was
      inversely correlated with gray matter volume in prefrontal cortex and tobacco
      intake was inversely correlated with gray matter volume in left temporal cortex.
      There were no significant interactions by group in any region. There is no
      evidence to support the hypothesis of increased susceptibility to harmful effects
      of drugs and alcohol on regional gray matter in ARMS subjects. However, alcohol,
      tobacco and cannabis at low to moderate intake may be associated with lower gray
      matter in both ARMS subjects and healthy volunteers-possibly representing low
      level cortical damage or change in neural plasticity.

PMID- 21741804
TI  - High dose hydrocortisone immediately after trauma may alter the trajectory of
      PTSD: interplay between clinical and animal studies.
AB  - High-dose corticosteroids have been reported to reduce symptoms of acute stress
      and post-traumatic stress in polytrauma patients and in animal studies. The
      underlying mechanism of action remains largely unclear. These issues were
      addressed in parallel in the clinical and preclinical studies below. In this
      preliminary study, 25 patients with acute stress symptoms were administered a
      single intravenous bolus of high-dose hydrocortisone (100-140 mg) or placebo
      within 6 h of a traumatic event in a prospective, randomized, double-blind,
      placebo-controlled pilot study. Early single high-dose hydrocortisone
      intervention attenuated the core symptoms of both the acute stress and of
      subsequent PTSD in patients. High-dose hydrocortisone treatment given in the
      first few hours after a traumatic experience was associated with significant
      favorable changes in the trajectory of exposure to trauma, as expressed by the
      reduced risk of the development of PTSD post-trauma. In parallel, a comparative
      study of morphological arborization in dentate gyrus and its modulating molecules
      was performed in stress-exposed animals treated with high-dose hydrocortisone.
      Steroid-treated stressed animals displayed significantly increased dendritic
      growth and spine density, with increased levels of brain-derived neurotrophic
      factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal
      study provided insights into the potential mechanism of this intervention, as it
      identified relevant morphological and biochemical associations to the clinical
      observations. Thus, evidence from clinical and animal studies suggests that there
      is a "window of opportunity" in the early aftermath of trauma to help those who
      are vulnerable to the development of chronic PTSD.

PMID- 21741805
TI  - TNF-alpha-stimulated macrophages protect A549 lung cells against iron and
      oxidation.
AB  - Previously, we have shown that TNF-alpha protects iron-exposed J774 macrophages
      against iron-catalyzed oxidative lysosomal disruption and cell death by
      increasing reduced glutathione and H-ferritin in cells. Because J774 cells are
      able to harbor large amounts of iron, which is potentially harmful in a redox
      active state, we hypothesized that TNF-alpha-stimulated J774 macrophages will
      prevent iron-driven oxidative killing of alveolar epithelial A549 cells in co
      culture. In the present study, iron trichloride (which is endocytosed by cells as
      hydrated iron-phosphate complexes) was mainly deposited inside the lysosomes of
      J774 macrophages, while A549 cells, equally iron exposed, accumulated much less
      iron. When challenged by oxidants, however, reactive lysosomal iron in A549 cells
      promoted lysosomal disruption and cell death, particularly in the presence of TNF
      alpha. This effect resulted from an elevation in ROS generation by TNF-alpha,
      while a compensatory upregulation of protective molecules (H-ferritin and/or
      reduced glutathione) by TNF-alpha was absent. A549 cell death was particularly
      pronounced when iron and TNF-alpha were present in the conditioned medium during
      oxidant challenge; thus, iron-driven oxidative reactions in the culture medium
      were a much greater hazard to A549 cells than those taking place inside their
      lysosomes. Consequently, the iron chelator, deferoxamine, efficiently prevented
      A549 cell death when added to the culture medium during an oxidant challenge. In
      co-cultures of TNF-alpha-stimulated lung cells, J774 macrophages sequestered iron
      inside their lysosomes and protected A549 cells from oxidative reactions and cell
      death. Thus, the collective effect of TNF-alpha on co-cultured lung cells was
      mainly cytoprotective.

PMID- 21741806
TI  - Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic
      injury in mice.
AB  - The possible protective effects of Chlorella vulgaris extract (CVE) on carbon
      tetrachloride (CCl(4))-induced acute hepatic injury in mice and the mechanism
      underlying these effects was investigated. CCl(4) administration caused a marked
      increase in the levels of serum aminotransferases, lipid peroxidation and
      cytochrome P450-2E1 (CYP450) expression. Also, decreased glutathione (GSH)
      content and activities of cellular antioxidant defense enzymes such as superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and glutathione-S
      transferase (GST) were found after CCl(4) exposure. All of these phenotypes were
      markedly reversed by preadministration of the mice with CVE. In addition, CVE
      exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in
      mouse liver homogenates, and on superoxide radical scavenging activity. Taken
      together, these results suggest that CVE produced a protective action on CCl(4)
      induced acute hepatic injury in mice, presumably through blocking CYP-mediated
      CCl(4) bioactivation, inducing the GSH levels, antioxidant enzyme activities and
      free radical scavenging effect. Therefore, CVE may be an effective
      hepatoprotective agent and viable candidate for treating hepatic disorders and
      other oxidative stress-related diseases.

PMID- 21741807
TI  - Inhibition of microbial arsenate reduction by phosphate.
AB  - The ratio of arsenite (As(III)) to arsenate (As(V)) in soils and natural waters
      is often controlled by the activity of As-transforming microorganisms. Phosphate
      is a chemical analog to As(V) and, consequently, may competitively inhibit
      microbial uptake and enzymatic binding of As(V), thus preventing its reduction to
      the more toxic, mobile, and bioavailable form - As(III). Five As-transforming
      bacteria isolated either from As-treated soil columns or from As-impacted soils
      were used to evaluate the effects of phosphate on As(V) reduction and As(III)
      oxidation. Cultures were initially spiked with various P:As ratios, incubated for
      approximately 48 h, and analyzed periodically for As(V) and As(III)
      concentration. Arsenate reduction was inhibited at high P:As ratios and
      completely suppressed at elevated levels of phosphate (500 and 1,000 MUM; P
      inhibition constant (K(i))~20-100 MUM). While high P:As ratios effectively shut
      down microbial As(V) reduction, the expression of the arsenate reductase gene
      (arsC) was not inhibited under these conditions in the As(V)-reducing isolate,
      Agrobacterium tumefaciens str. 5B. Further, high phosphate ameliorated As(V)
      induced cell growth inhibition caused by high (1mM) As pressure. These results
      indicate that phosphate may inhibit As(V) reduction by impeding As(V) uptake by
      the cell via phosphate transport systems or by competitively binding to the
      active site of ArsC.

PMID- 21741808
TI  - Unexpected bilateral increase of cerebral regional saturation of oxygen as an
      early warning sign of air embolism.

PMID- 21741809
TI  - Devastating intracardiac and aortic thrombosis: a case report of apparent
      catastrophic antiphospholipid syndrome during liver transplantation.
AB  - Fewer than 80 cases of intracardiac thrombosis and intraoperative pulmonary
      thromboembolism during liver transplantation have been described. We present a
      patient who suffered an intraoperative fulminant intracardiac and aortic
      thrombosis and posthumously was found to have had high anticardiolipin
      immunoglobulin M concentration and markers of hyperfibrinolysis in preoperatively
      collected plasma. Hemostatic therapy in the presence of circulating
      antiphospholipid antibodies and the pathogenesis of a catastrophic
      antiphospholipid syndrome are discussed.

PMID- 21741810
TI  - Perioperative management of von Willebrand disease: a review for the
      anesthesiologist.
AB  - von Willebrand disease (VWD) is the most common hereditary bleeding disorder in
      humans, with an estimated prevalence of 0.5% to 1%. Patients with VWD are at
      increased risk of perioperative bleeding complications. This review provides an
      evidence-based overview of VWD and its management during the perioperative
      period.

PMID- 21741811
TI  - Supraglottic jet ventilation assists intubation in a Marfan's syndrome patient
      with a difficult airway.
AB  - A 37 year old woman with Marfan's syndrome underwent an elective gynecologic
      procedure. Mask ventilation was not difficult but initial direct laryngoscopy
      showed no view of the glottic opening. The patient's trachea was quickly and
      successfully intubated using a supraglottic jet ventilation technique. The
      technique provided oxygenation and ventilation during intubation and assisted
      intubation of a patient with a grade III glottic view. No hypoxia or barotrauma
      were noted during the intubation.

PMID- 21741812
TI  - Acute hypopituitarism in a pregnant patient after cardiac gunshot injury.
AB  - Sheehan's syndrome is a well described entity that refers to hypopituitarism with
      pituitary infarction secondary to postpartum shock or hemorrhage. Antepartum
      pituitary infarction is a very rare condition that has been reported only in
      patients with longstanding type 1 diabetes mellitus or uncontrolled gestational
      diabetes. A case of severe, acute hypopituitarism in the setting of hemorrhagic
      shock from a gunshot wound is presented. Our case report highlights the
      importance of including hypopituitarism in the differential diagnosis of a
      critically ill parturient.

PMID- 21741813
TI  - The optimal effect-site concentration of remifentanil for lightwand tracheal
      intubation during propofol induction without muscle relaxation.
AB  - STUDY OBJECTIVE: To determine the most suitable effect-site concentration of
      remifentanil during lightwand intubation when administered with a target
      controlled infusion (TCI) of propofol at 4.0 MUg/mL without neuromuscular
      blockade. DESIGN: Prospective study using a modified Dixon's up-and-down method.
      SETTING: Operating room of an academic hospital. PATIENTS: 28 ASA physical status
      1 and 2 patients, aged 18-65 years, scheduled for minor elective surgery.
      INTERVENTIONS: Anesthesia was induced by TCI propofol effect-site concentration
      to 4.0 MUg/mL, and the dose of remifentanil given to each patient was determined
      by the response of the previously tested patient using 0.2 ng/mL as a step size.
      The first patient was tested at a target effect-site concentration of 4.0 ng/mL
      of remifentanil. If intubation was successful, the remifentanil dose was
      decreased by 0.2 ng/mL; if it failed, the remifentanil dose was increased by 0.2
      ng/mL. Successful intubation was defined as excellent or good intubating
      conditions. MEASUREMENTS AND MAIN RESULTS: The remifentanil effect-site
      concentration was measured. The optimal effect-site concentration of remifentanil
      for lightwand tracheal intubation during propofol induction using 2% propofol
      target effect-site concentration to 4 MUg/mL was 2.16 +/- 0.19 ng/mL. From probit
      analysis, the effect-site concentration of remifentanil required for successful
      lightwand intubation in 50% (EC50) and 95% (EC95) of adults was 2.11 ng/mL (95%
      CI 1.16-2.37 ng/mL) and 2.44 ng/mL (95% CI 2.20-3.79 ng/mL), respectively.
      CONCLUSION: A remifentanil effect-site concentration of 2.16 +/- 0.19 ng/mL given
      before a propofol effect-site concentration of 4 MUg/mL allowed lightwand
      intubation without muscle relaxant.

PMID- 21741814
TI  - Impact of a transient instability of the ecstasy market on health concerns and
      drug use patterns in The Netherlands.
AB  - BACKGROUND: A recent decline in MDMA-like substances in ecstasy tablets has been
      reported by a number of countries in the European Union. This study describes the
      instability of the ecstasy market in The Netherlands during 2008 and 2009, and
      investigates whether this had any impact on drug testing or patterns of drug use.
      METHODS: The health concerns of drug users handing in drug samples at drug
      testing facilities was measured using intervention time-series analysis. In
      addition, these ecstasy users were asked about changes in their drug use.
      RESULTS: Nationally, the unstable market situation for ecstasy has increased the
      number of users handing in ecstasy tablets for testing because of health concern.
      There was no change in the number of users handing in cocaine or gamma
      hydroxybutyrate (GHB). Respondents reported no major changes in their drug use
      resulting from the shortage of MDMA-like substances. CONCLUSIONS: These findings
      provide further insight in drug policy based on both harm reduction and use
      reduction. In the event of reduced ecstasy quality, ecstasy users in The
      Netherlands have increasingly used drug testing as a potential harm reduction
      tool, rather than changing their patterns of drug use. This might indicate that a
      transient reduction of drug quality does not serve as a good drug use reduction
      strategy for ecstasy users.

PMID- 21741815
TI  - Heroin users' views and experiences of physical activity, sport and exercise.
AB  - BACKGROUND: Although there is limited research on heroin users' participation in
      physical activity, sport and exercise, public health literature asserts that
      being physically active is good for individuals. Critics, however, caution that
      the benefits of sport and exercise are overstated and sport may itself reinforce
      or create inequalities. METHODS: In-depth interviews were conducted with 40
      current or ex-heroin users, of whom 37 were re-interviewed three months later.
      Data from all 77 interviews were analysed to explore individuals' self-reported
      participation in physical activity, sport and exercise; their desire to
      participate; and any barriers to participation experienced. FINDINGS:
      Participants were very interested in sport and exercise and engaged in a wide
      variety of active pastimes. Although they did little structured sport or exercise
      during periods of heavy heroin use, they still often walked or cycled. Enjoyment
      was a key feature of being physically active in treatment and in early recovery.
      Additionally, individuals reported diverse health and social gains and felt that
      sport and exercise helped them to reduce their heroin use. These benefits
      notwithstanding, there were personal, social and structural barriers to being
      active and so individuals were generally keen to take advantage of any sport or
      exercise opportunities offered to them by services. CONCLUSIONS: By focusing on
      the meanings that heroin users themselves attribute to being active, our analyses
      reveal that members of this population derive great pleasure from all manner of
      physical pastimes. A small but growing literature on embodied sporting practices
      helps us to interpret this. We conclude that there is an important role for
      physical activity, sport and exercise within policy and practice responses to
      heroin use, but with a need to be creative and flexible regarding the kinds of
      activities promoted.

PMID- 21741816
TI  - Changes in mineralogical and leaching properties of converter steel slag
      resulting from accelerated carbonation at low CO2 pressure.
AB  - Steel slag can be applied as substitute for natural aggregates in construction
      applications. The material imposes a high pH (typically 12.5) and low redox
      potential (Eh), which may lead to environmental problems in specific application
      scenarios. The aim of this study is to investigate the potential of accelerated
      steel slag carbonation, at relatively low pCO2 pressure (0.2 bar), to improve the
      environmental pH and the leaching properties of steel slag, with specific focus
      on the leaching of vanadium. Carbonation experiments are performed in laboratory
      columns with steel slag under water-saturated and -unsaturated conditions and
      temperatures between 5 and 90  degrees C. Two types of steel slag are tested;
      free lime containing (K3) slag and K1 slag with a very low free lime content. The
      fresh and carbonated slag samples are investigated using a combination of
      leaching experiments, geochemical modelling of leaching mechanisms and
      microscopic/mineralogical analysis, in order to identify the major processes that
      control the slag pH and resulting V leaching. The major changes in the amount of
      sequestered CO2 and the resulting pH reduction occurred within 24h, the free lime
      containing slag (K3-slag) being more prone to carbonation than the slag with
      lower free lime content (K1-slag). While carbonation at these conditions was
      found to occur predominantly at the surface of the slag grains, the formation of
      cracks was observed in carbonated K3 slag, suggesting that free lime in the
      interior of slag grains had also reacted. The pH of the K3 slag (originally pH+/
      12.5) was reduced by about 1.5 units, while the K1 slag showed a smaller decrease
      in pH from about 11.7 to 11.1. However, the pH reduction after carbonation of the
      K3 slag was observed to lead to an increased V-leaching. Vanadium leaching from
      the K1 slag resulted in levels above the limit values of the Dutch Soil Quality
      Decree, for both the untreated and carbonated slag. V-leaching from the
      carbonated K3 slag remained below these limit values at the relatively high pH
      that remained after carbonation. The V-bearing di-Ca silicate (C2S) phase has
      been identified as the major source of the V-leaching. It is shown that the
      dissolution of this mineral is limited in fresh steel slag, but strongly enhanced
      by carbonation, which causes the observed enhanced release of V from the K3 slag.
      The obtained insights in the mineral transformation reactions and their effect on
      pH and V-leaching provide guidance for further improvement of an accelerated
      carbonation technology.

PMID- 21741817
TI  - Pulse-driven magnetoimpedance sensor detection of biomagnetic fields in
      musculatures with spontaneous electric activity.
AB  - We measured biomagnetic fields in musculatures with spontaneous electric activity
      using a pulse-driven magnetoimpedance (PMI) sensor with the sensitivity improved
      toward a pico-Tesla (pT) level. Due to the sufficiently short operation interval
      of 1 MUs, this magnetic sensor enabled quasi-real time recordings of the magnetic
      field for biological electric activity. Isolated small musculatures from the
      guinea-pig stomach, taenia caeci, portal vein and urinary bladder were incubated
      in an organ bath at a body temperature. The improved PMI sensor mounted
      approximately 1mm below the preparations detected oscillatory magnetic fields
      reflecting spontaneous electric activities of musculature preparations. In the
      taenia caeci, application of tetraethyl ammonium (TEA), a K(+) channel blocker,
      significantly enhanced the magnetic activity estimated by histogram analysis.
      Also, in some musculature preparations, simultaneous measurements with electric
      activity revealed that the observed magnetic activities were attributed to
      biological electric activity. PMI technology is promising for applications in
      biology and medicine.

PMID- 21741818
TI  - Application of hyperthermophiles and their enzymes.
AB  - Enzymes from hyperthermophiles display extreme (thermo)stability and a wide range
      of enzymes have been examined to explore their potential for various
      biotechnological processes. In addition, recent years have witnessed the
      development of genetic systems in a number of hyperthermophilic archaea. This has
      provided the means to initiate cell engineering studies in these organisms.
      Biofuel production is now an important topic in microbial biotechnology, and the
      hydrogen producing capabilities of (hyper)thermophiles, as well as their
      thermostable hydrogenases, are now attracting much attention.

PMID- 21741819
TI  - Characterization of responses of 2d array seven29 detector and its combined use
      with octavius phantom for the patient-specific quality assurance in rapidarc
      treatment delivery.
AB  - A commercial 2D array seven29 detector has been characterized and its performance
      has been evaluated. 2D array ionization chamber equipped with 729 ionization
      chambers uniformly arranged in a 27 * 27 matrix with an active area of 27 * 27
      cm2 was used for the study. An octagon-shaped phantom (Octavius Phantom) with a
      central cavity is used to insert the 2D ion chamber array. All measurements were
      done with a linear accelerator. The detector dose linearity, reproducibility,
      output factors, dose rate, source to surface distance (SSD), and directional
      dependency has been studied. The performance of the 2D array, when measuring
      clinical dose maps, was also investigated. For pretreatment quality assurance, 10
      different RapidArc plans conforming to the clinical standards were selected. The
      2D array demonstrates an excellent short-term output reproducibility. The long
      term reproducibility was found to be within +/-1% over a period of 5 months.
      Output factor measurements for the central chamber of the array showed no
      considerable deviation from ion chamber measurements. We found that the 2D array
      exhibits directional dependency for static fields. Measurement of beam profiles
      and wedge-modulated fields with the 2D array matched very well with the ion
      chamber measurements in the water phantom. The study shows that 2D array seven29
      is a reliable and accurate dosimeter and a useful tool for quality assurance. The
      combination of the 2D array with the Octavius phantom proved to be a fast and
      reliable method for pretreatment verification of rotational treatments.

PMID- 21741820
TI  - Comparison of setup error using different reference images: a phantom and lung
      cancer patients study.
AB  - The purpose of this study was to compare setup errors obtained with kilovoltage
      cone-beam computed tomography (CBCT) and 2 different kinds of reference images,
      free-breathing 3D localization CT images (FB-CT) and the average images of 4-D
      localization CT images (AVG-CT) for phantom and lung cancer patients. This study
      also explored the correlation between the difference of translational setup
      errors and the gross tumor volume (GTV) motion. A respiratory phantom and 14
      patients were enrolled in this study. For phantom and each patient, 3D helical CT
      and 4D CT images were acquired, and AVG-CT images were generated from the 4D CT.
      The setup errors were determined based on the image registration between the CBCT
      and the 2 different reference images, respectively. The data for both
      translational and rotational setup errors were analyzed and compared. The GTV
      centroid movement as well as its correlation with the translational setup error
      differences was also evaluated. In the phantom study, the AVG-CT method was more
      accurate than the FB-CT method. For patients, the translational setup errors
      based on FB-CT were significantly larger than those from AVG-CT in the left-right
      (LR), superior-inferior (SI), and anterior-posterior (AP) directions (p < 0.05).
      Translational setup errors differed by >1 mm in 32.6% and >2 mm in 12.9% of CBCT
      scans. The rotational setup errors from FB-CT were significantly different from
      those from AVG-CT in the LR and AP directions (p < 0.05). The correlation
      coefficient of the translational setup error differences and the GTV centroid
      movement in the LR, SI, and AP directions was 0.515 (p = 0.060), 0.902 (p <
      0.001), and 0.510 (p = 0.062), respectively. For lung cancer patients,
      respiration may affect the on-line target position location. AVG-CT provides
      different reference information than FB-CT. The difference in SI direction caused
      by the 2 methods increases with the GTV movement. Therefore, AVG-CT should be the
      prefered choice of reference images.

PMID- 21741821
TI  - Impact of MLC leaf width on the quality of the dose distribution in partial
      breast irradiation.
AB  - Partial-breast irradiation (PBI) aims to limit the target volume for radiotherapy
      in women with early breast cancer after partial mastectomy to the region at
      highest risk of local recurrence, the tumor bed. Multileaf collimators are used
      to achieve conformal radiation beam portals required for PBI. Narrower leaf
      widths are generally assumed to allow more conformal shaping of beam portals
      around irregularly shaped target volumes. The aim was to compare 5-mm and 10-mm
      leaf widths for patients previously treated using PBI and assess subsequent
      planning target volume (PTV) coverage and organ at risk (OAR) doses for 16
      patients. Several plans (5-mm leaf width or 10-mm leaf width) were generated for
      each patient using the original treated plan as the basis for attempts at further
      optimization. Alternating between different leaf widths found no significant
      difference in terms of overall PTV coverage and OAR doses between treatment
      plans. Optimization of the original treated plan allowed a small decrease in
      ipsilateral breast dose, which was offset by a lower PTV minimum. No significant
      dosimetric difference was found to support an advantage of 5-mm over 10-mm leaf
      width in this setting.

PMID- 21741822
TI  - Consistency of vendor-specified activity values for 192Ir brachytherapy sources.
AB  - A long-term comparison was done between the manufacturer-stated 192Ir activity
      and the measured 192Ir activities determined with a well-type ionization chamber.
      Sources for a Nucletron Micro Selectron high-dose-rate (HDR) unit were used for
      this purpose. The radioactive sources reference activities were determined using
      a PTW well-type ionization chamber traceable to the National Institute of
      Standards and Technology Primary Calibration Laboratory. The measurements were
      taken in a period of 56 months with 17 different radioactive sources. The
      manufacturer stated activities were taken from the source calibration certificate
      provided by the manufacturer. These values were compared with the measured
      activities. The results have shown that both the percentage deviation of the
      monthly control measurements with the well-type chamber and the ratio between the
      measured activities to the manufacturer-stated value lie within +/- 2.5%. These
      results were compared with similar published data and with uncertainty level (3%
      of the mean and 5% maximum deviation from mean) for brachytherapy sources
      calibration recommended by the AAPM. It was concluded that a threshold level of
      +/-2.5% can be used as a suitable quality assurance indicator to spot problems in
      our department. The typical +/-5% uncertainty as provided by the manufacturers
      may be tightened to +/-3% to be more in line with published AAPM reports.

PMID- 21741823
TI  - Not just the messenger: RNA takes control.

PMID- 21741824
TI  - Melanoma antigen family A identified by the bimodality index defines a subset of
      triple negative breast cancers as candidates for immune response augmentation.
AB  - BACKGROUND: Molecular markers displaying bimodal expression distribution can
      reveal distinct disease subsets and may serve as prognostic or predictive markers
      or represent therapeutic targets. Oestrogen (ER) and human epidermal growth
      factor receptor 2 (HER2) receptors are strongly bimodally expressed genes in
      breast cancer. MATERIAL AND METHODS: We applied a novel method to identify
      bimodally expressed genes in 394 triple negative breast cancers (TNBC). We
      identified 133 bimodally expressed probe sets (128 unique genes), 69 of these
      correlated to previously reported metagenes that define molecular subtypes within
      TNBC including basal-like, molecular-apocrine, claudin-low and immune cell rich
      subgroups but 64 probe sets showed no correlation with these features. RESULTS:
      The single most prominent functional group among these uncorrelated genes was the
      X chromosome derived Cancer/Testis Antigens (CT-X) including melanoma antigen
      family A (MAGE-A) and Cancer/Testis Antigens (CTAG). High expression of CT-X
      genes correlated with worse survival in multivariate analysis (HR 2.02, 95% CI
      1.27-3.20; P=0.003). The only other significant variable was lymph node status.
      The poor prognosis of patients with high MAGE-A expression was ameliorated by the
      concomitant high expression of immune cell metagenes (HR 1.87, 95% CI 0.96-3.64;
      P=0.060), whereas the same immune metagene had lesser prognostic value in TNBC
      with low MAGE-A expression. CONCLUSIONS: MAGE-A antigen defines a very aggressive
      subgroup of TNBC; particularly in the absence of immune infiltration in the
      tumour microenvironment. These observations suggest a therapeutic hypothesis;
      TNBC with MAGE-A expression may benefit the most from further augmentation of the
      immune response. Novel immune stimulatory drugs such as (anti-cytotoxic T
      lymphocyte antigen-4 CTLA-4) directed therapies provide a realistic opportunity
      to directly test this hypothesis in the clinic.

PMID- 21741825
TI  - Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in
      patients with early-stage breast cancer.
AB  - BACKGROUND: Racial disparities in breast cancer outcomes are attributed to
      differences in baseline tumour characteristics and biology, stage, age, ethnic
      background and socioeconomic factors. However, little is known about racial
      differences in treatment-related toxicities. We hypothesised that racial/ethnic
      differences result in differential tolerance to chemotherapy potentially, leading
      to compromised dose intensity/density of chemotherapy in patients with early
      stage breast cancer. METHODS: Data were collected from patients treated at five
      international centers for early breast cancer with the same adjuvant/neoadjuvant
      chemotherapy (FEC 100: fluorouracil 500mg/m(2), epirubicin 100mg/m(2), and
      cyclophosphamide 500mg/m(2),every 21d for 3-6 cycles). Toxicities were assessed
      by first episode of ?grade 2 toxicity. RESULTS: Toxicities were compared
      according to four race/ethnicity groups (103 Caucasian, 30 African American, 164
      Asian, and 34 Hispanic patients). Tumour characteristics across four
      race/ethnicity groups were similar. Asians had a significantly higher rate of
      grade 3 haematologic toxicity than Caucasians, African Americans or Hispanic
      women (32%, 16%, 10%, and 15%, respectively; p<0.05). In multivariate analysis,
      only lower BMI was associated with a higher incidence of ?grade 3 toxicities.
      However, no significant differences in chemotherapy dose intensity/density were
      shown across the four race/ethnicity groups. CONCLUSION: Racial differences in
      acute toxicity were noted in women with breast cancer who were treated with FEC
      100 chemotherapy, suggesting that extrapolating toxicities from chemotherapy
      across ethnicities is not possible and emphasising the need to validate safety of
      chemotherapeutic regimens in patients of different ethnicities by enhancing the
      participation of minorities in clinical trials.

PMID- 21741826
TI  - Examining five- and ten-year survival in older women with breast cancer using
      cancer-specific geriatric assessment.
AB  - PURPOSE: To examine five- and ten-year survival based on cancer-specific
      geriatric assessment (C-SGA) in older women with early stage breast cancer.
      METHODS: We evaluated 660 women >=65-years old diagnosed with stage I-IIIA
      primary breast cancer and attending physician permission to contact in four
      geographic regions in the United States of America (USA). Data were collected
      over ten-years of follow-up from consenting women's medical records, telephone
      interviews, National Death Index and Social Security Death Index. C-SGA was
      described by four domains using six measures: socio-demographic (financial
      resources); clinical (comorbidity, obesity); function (physical function
      limitations); and psychosocial (general mental health, social support). Survival
      from all-cause and breast-cancer-specific mortality and receipt of guideline
      recommended therapy was assessed for different groups of subjects with C-SGA
      domain deficits (cut-off >=3 deficits). RESULTS: The proportion of women with >=3
      C-SGA deficits surviving ten-years was consistently statistically significantly
      lower (all-cause 26% versus 46% and breast-cancer-specific 76% versus 89%,
      p<=0.04). The proportion significantly decreased as number of C-SGA deficits
      increased (linear trend p<0.0001). Receipt of guideline-recommended therapy
      decreased with age but not consistently by number of C-SGA deficits. The all
      cause and breast-cancer-specific death rate at five- and ten-years was
      consistently approximately two times higher in women with >=3 C-SGA deficits even
      when fully adjusted for confounding factors (HR(5-yrAllCauseFullyAdjusted)=1.87
      [1.36-2.57], HR(10-yrAllCauseFullyAdjusted)=1.74 [1.35-2.15], HR(5
      yrBreastCancerFullyAdjusted)=1.95 [1.18-3.20], HR(10
      yrBreastCancerFullyAdjusted)=1.99 [1.21-3.28]). CONCLUSION: Regardless of age and
      stage of disease, C-SGA predicts five- and ten-year all-cause and breast-cancer
      specific survival in older women. Hence, C-SGA may provide an effective strategy
      to guide treatment decision-making and to identify risk factors for intervention.

PMID- 21741827
TI  - Association between c-myc amplification and pathological complete response to
      neoadjuvant chemotherapy in breast cancer.
AB  - BACKGROUND: The aim of this study was to investigate whether c-myc amplification
      in human breast cancer is associated with response to neoadjuvant chemotherapy
      comprising paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC).
      METHODS: Tumour tissue samples were obtained before neoadjuvant chemotherapy (P
      FEC) from 100 primary breast cancer patients (stage II/III). C-myc and HER2
      amplification were examined by FISH, and oestrogen receptor (ER), progesterone
      receptor (PR), Ki67, and topoisomerase 2alpha (TOP2A) expression were examined
      immunohistochemically. Pathological complete response (pCR) was defined by a
      complete loss of tumour cells in the breast without any lymph node metastasis.
      RESULTS: C-myc amplification was observed in 40% (40/100) of breast tumours, and
      was significantly associated with ER-negative tumours (23/40 for ER(-) versus
      17/60 for ER(+), P=0.004), high histological grade tumours (11/18 for grade 3
      versus 29/82 for grades 1+2, P=0.043) and TOP2A-positive tumours (28/51 for
      TOP2A(+) versus 12/49 for TOP2A(-), P=0.002). pCR rate was 20% for total patients
      (10.0% for ER(+) and 35.0% for ER(-)). Further, breast tumours with c-myc
      amplification (c-myc(+)) showed a significantly (P=0.041) higher pCR rate (12/40)
      than those without such amplification (c-myc(-)) (8/60). This association between
      pCR and c-myc amplification was observed in ER-positive tumours (4/17 for c
      myc(+) versus 2/43 for c-myc(-), P=0.048) but not in ER-negative tumours (8/23
      for c-myc(+) versus 6/17 for c-myc(-), P=0.973). CONCLUSION: Our results suggest
      that c-myc amplification is significantly associated with a high pCR rate to P
      FEC in breast tumours, especially in ER-positive tumours.

PMID- 21741828
TI  - p63 Transcriptionally regulates BNC1, a Pol I and Pol II transcription factor
      that regulates ribosomal biogenesis and epithelial differentiation.
AB  - The p53-family member, p63 is a transcription factor that influences cellular
      adhesion, motility, proliferation, survival and apoptosis, and has a major role
      in regulating epithelial stem cells. Expression of p63 is often dysregulated in
      squamous cell carcinomas of the head and neck. In this study we show that p63
      induces the expression of the basal epithelial transcription factor, Basonuclin
      1. Basonuclin 1 is an unusual transcription factor that interacts with a subset
      of promoters of genes that are transcribed by both RNA polymerase-I and -II and
      has roles in maintaining ribosomal biogenesis and the proliferative potential of
      immature epithelial cells. Chromatin immunoprecipitation and reporter assays
      demonstrate that Basonuclin 1 is a direct transcriptional target of p63 and we
      also show that up-regulation of Basonuclin 1 is a common event in squamous cell
      carcinomas of the head and neck. These data identify a new transcriptional
      programme mediated by p63 regulation of the Basonuclin 1 transcription factor in
      squamous cell carcinomas and provide a novel link of p63 with the regulation of
      ribosomal biogenesis in epithelial cancer.

PMID- 21741829
TI  - Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05
      phase III study in HER2-positive breast cancer.
AB  - BACKGROUND: Continuation of trastuzumab plus capecitabine (XH) showed a
      significantly improved overall response rate and time to progression compared
      with capecitabine (X) alone in women with HER2-positive breast cancer progressing
      during trastuzumab treatment. Here, we report the final analysis on overall
      survival. PATIENTS AND METHODS: Patients with HER2-positive, advanced breast
      cancer who progressed during treatment with trastuzumab with or without 1st-line
      metastatic chemotherapy were prospectively randomised to X (2500mg/m(2) on days 1
      14, q3w) or XH (6 (8)mg/kg, q3w). Overall survival was a pre-specified secondary
      end-point. RESULTS: Median follow-up at June 2010 was 20.7months. Fifty nine of
      74 and 60 of 77 patients died in the X and XH arm, respectively. Median overall
      survival was 20.6 and 24.9months with X and XH, respectively (HR=0.94 [0.65
      1.35]; p=0.73). Performance status and metastatic site were independent
      prognosticators for overall survival. No difference between treatment arms was
      observed for patients who achieved clinical response or clinical benefit,
      respectively. Patients who continued/restarted anti-HER2 treatment (trastuzumab
      or lapatinib) after 2nd progression (N=52) had a post-progression survival of
      18.8 compared with 13.3months for those who did not receive 3rd line treatment
      with anti-HER2 agents (N=88) (HR 0.63; p=0.02). CONCLUSIONS: Final overall
      survival analysis of the GBG-26 study did not demonstrate a significant survival
      benefit for treatment beyond progression with trastuzumab. However, in a post-hoc
      analysis, patients receiving anti-HER2 treatment as 3rd line therapy showed a
      better post-progression survival than those not receiving this targeted
      treatment.

PMID- 21741830
TI  - A comparison of international breast cancer guidelines - do the national
      guidelines differ in treatment recommendations?
AB  - AIM OF THE STUDY: Clinical practice guidelines (CPG) are an appropriate method to
      optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of
      breast cancer have been developed by national health institutions or medical
      societies. While a comparison of methodological criteria has been undertaken
      before, it is unknown whether these CPGs differ in their actual treatment
      recommendations. METHODS: We included national breast cancer CPGs from the USA,
      Canada, Australia, the UK, and Germany that satisfy internationally recognised
      methodological criteria and are in widespread use in daily clinical care.
      Treatment recommendations for adjuvant invasive breast cancer including surgery,
      radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared.
      RESULTS: Recommendations for endocrine therapy show discordances regarding
      optimal usage of ovarian function suppression for premenopausal patients and
      aromatase inhibitors for postmenopausal patients. However, most other treatment
      recommendations exhibit a large degree of congruency. This reflects the fact that
      they rest on the same evidence base, and that many national guidelines are
      adopted from other guidelines so that well accepted guidelines are cited within
      other guidelines. CONCLUDING STATEMENT: Considering that the development of
      guidelines is a very expensive and resource-intensive task the question arises
      whether the development of national guidelines in numerous countries is worth the
      effort since the recommendations differ only marginally.

PMID- 21741831
TI  - The cost-effectiveness of adjuvant chemotherapy for early breast cancer: A
      comparison of no chemotherapy and first, second, and third generation regimens
      for patients with differing prognoses.
AB  - BACKGROUND: The risk of recurrence following surgery in women with early breast
      cancer varies, depending upon prognostic factors. Adjuvant chemotherapy reduces
      this risk; however, increasingly effective regimens are associated with higher
      costs and toxicity profiles, making it likely that different regimens may be cost
      effective for women with differing prognoses. To investigate this we performed a
      cost-effectiveness analysis of four treatment strategies: (1) no chemotherapy,
      (2) chemotherapy using cyclophosphamide, methotrexate, and fluorouracil (CMF) (a
      first generation regimen), (3) chemotherapy using Epirubicin-CMF (E-CMF) or
      fluorouracil, epirubicin, and cyclophosphamide (FEC60) (a second generation
      regimens), and (4) chemotherapy with FEC60 followed by docetaxel (FEC-D) (a third
      generation regimen). These adjuvant chemotherapy regimens were used in three
      large UK-led randomised controlled trials (RCTs). METHODS: A Markov model was
      used to simulate the natural progression of early breast cancer and the impact of
      chemotherapy on modifying this process. The probability of a first recurrent
      event within the model was estimated for women with different prognostic risk
      profiles using a parametric regression-based survival model incorporating
      established prognostic factors. Other probabilities, treatment effects, costs and
      quality of life weights were estimated primarily using data from the three UK-led
      RCTs, a meta-analysis of all relevant RCTs, and other published literature. The
      model predicted the lifetime costs, quality adjusted life years (QALYs) and cost
      effectiveness of the four strategies for women with differing prognoses.
      Sensitivity analyses investigated the impact of uncertain parameters and model
      assumptions. FINDINGS: For women with an average to high risk of recurrence
      (based upon prognostic factors and any other adjuvant therapies received), FEC-D
      appeared most cost-effective assuming a threshold of L20,000 per QALY for the
      National Health Service (NHS). For younger low risk women, E-CMF/FEC60 tended to
      be the optimal strategy and, for some older low risk women, the model suggested a
      policy of no chemotherapy was cost-effective. For no patient group was CMF
      chemotherapy the preferred option. Sensitivity analyses demonstrated cost
      effectiveness results to be particularly sensitive to the treatment effect
      estimate for FEC-D and the future price of docetaxel. INTERPRETATION: To our
      knowledge, this analysis is the first cost-effectiveness comparison of no
      chemotherapy, and first, second, and third generation adjuvant chemotherapy
      regimens for early breast cancer patients with differing prognoses. The results
      demonstrate the potential for different treatment strategies to be cost-effective
      for different types of patients. These findings may prove useful for policy
      makers attempting to formulate cost-effective treatment guidelines in the field
      of early breast cancer.

PMID- 21741832
TI  - Hepatic resection for metastatic breast cancer: a systematic review.
AB  - BACKGROUND: Systemic chemotherapy is the mainstay of treatment for metastatic
      breast cancer with the role of surgery being strictly limited for palliation of
      metastatic complications or locoregional relapse. An increasing number of studies
      examining the role of therapeutic hepatic metastasectomy show encouraging
      survival results. A systematic review was undertaken to define its safety,
      efficacy and to identify prognostic factors associated with survival. METHODS:
      Electronic search of the MEDLINE and PubMed databases (January 2000-January 2011)
      to identify studies reporting outcomes of hepatectomy for breast cancer liver
      metastases (BCLM) with hepatectomy was undertaken. Two reviewers independently
      appraised each study using a predetermined protocol. Safety and clinical efficacy
      was synthesised through a narrative review with full tabulation of results of all
      included studies. RESULTS: Nineteen studies were examined. This comprised of 553
      patients. Hepatectomy for BCLM was performed at a rate of 1.8 (range, 0.7-7.7)
      cases per year in reported series. The median time to liver metastases occurred
      at a median of 40 (range, 23-77) months. The median mortality and complication
      rate were 0% (range, 0-6%) and 21% (range, 0-44%), respectively. The median
      overall survival was 40 (range, 15-74) months and median 5-year survival rate was
      40% (range, 21-80%). Potential prognostic factors associated with a poorer
      overall survival include a positive liver surgical margin and hormone refractory
      disease. CONCLUSION: Hepatectomy is rarely performed for BCLM but the studies
      described in this review indicate consistent results with superior 5-year
      survival for selected patients with isolated liver metastases and in those with
      well controlled minimal extrahepatic disease. To evaluate its efficacy and
      control for selection bias, a randomised trial of standard chemotherapy with or
      without hepatectomy for BCLM is warranted.

PMID- 21741833
TI  - Synthesis of rotenoid derivatives with cytotoxic and topoisomerase II inhibitory
      activities.
AB  - 6-Deoxyclitoriacetal (1) and a series of 11 further derivatives of it (2-12) were
      synthesized and evaluated for their cytotoxic and topoisomerase IIalpha
      inhibitory activities. Compounds bearing epoxide (2), morpholine (6) and
      benzylamine (10) moieties showed promising in vitro cytotoxic activities against
      four cancer cell lines, with IC(50) values ranging from 0.38 to 0.73 MUM. These
      three compounds also strongly inhibited topoisomerase II activity at 68.3-93.5%
      and showed a moderately high DNA intercalating property.

PMID- 21741834
TI  - Design, synthesis and docking studies on benzamide derivatives as histone
      deacetylase inhibitors.
AB  - A series of benzamide derivatives including two scaffolds were designed and
      synthesized as potential histone deacetylase inhibitors. Most of synthesized
      compounds showed moderate enzymatic potency at the same order of magnitude, and
      compound 12b possessed better potency to the positive control (3.8 MUM vs 13.0
      MUM). It also showed a 50-fold increase in vitro anticancer activity against DU
      145 cell-lines. Molecular docking studies were carried out and used to explain
      the structure-activity relationships observed in vitro. Then we found that the
      cavity surrounded by ASP104, HIS33, PRO34 and PHE155 may be crucial for the
      inhibitors' activity. The docking results provide some useful information for
      future design of more potent inhibitors.

PMID- 21741835
TI  - Structure-activity relationship studies of novel pyrazole and imidazole
      carboxamides as cannabinoid-1 (CB1) antagonists.
AB  - The synthesis and biological evaluation of novel pyrazole and imidazole
      carboxamides as CB1 antagonists are described. As a part of eastern amide SAR,
      various chemically diverse motifs were introduced on rimonabant template. The
      central pyrazole core was also replaced with its conformationally constrained
      motif and imidazole moieties. In general, a range of modifications were well
      tolerated. Several molecules with low- and sub-nanomolar potencies were
      identified as potent CB1 receptor antagonists. The in vivo proof of principle for
      weight loss is demonstrated with a lead compound in DIO mice model.

PMID- 21741836
TI  - New branching inhibitors and their potential as strigolactone mimics in rice.
AB  - Strigolactones (SLs) are rhizosphere communication chemicals. Recent studies of
      highly branched mutants revealed that SL or its metabolites work as a
      phytohormone to inhibit shoot branching. When SLs are exogenously applied to the
      rice d10-1 mutant that has a highly branched phenotype caused by a defect in the
      SL biosynthesis gene (CCD8), they inhibit tiller bud outgrowth (branching in
      rice) of the mutant. We focused our attention on the SL function as a
      phytohormone and tried to find new chemicals mimicking the hormonal action of SL
      by screening chemicals that inhibit branching of rice d10-1 mutant. Fortunately,
      we found 5-(4-chlorophenoxy)-3-methylfuran-2(5H)-one (3a) as a new chemical
      possessing SL-like activity against the rice d10-1 mutant. Then, we prepared
      several derivatives of 3a (3b-3k) to examine their ability to inhibit shoot
      branching of rice d10-1. These derivatives were synthesized by a one-pot coupling
      reaction between phenols and halo butenolide to give 5-phenoxy 3-methylfuran
      2(5H)-one (3) derivatives, which possess a common substructure with SLs. Some of
      the derivatives showed SL-like activity more potently than GR24, a typical SL
      derivative, in a rice assay. As SLs also show activity by inducing seed
      germination of root parasitic plants, the induction activity of these derivatives
      was also evaluated. Here we report the structure-activity relationships of these
      compounds.

PMID- 21741837
TI  - Synthesis and cytotoxicity of the depsipeptides analogues of callipeltin B.
AB  - Solid phase synthesis of the cyclic depsipeptides of callipeltin B analogues and
      evaluation of cytotoxicity of synthetic peptides are described. We attempted to
      synthesize cyclic depsipeptides via the esterification or the amide bond
      formation for cyclization steps. In the assay of synthetic peptides, the linear
      peptide (10) exhibited modest cytotoxicity against HeLa cells.

PMID- 21741838
TI  - Design and pharmacological evaluation of PF-4840154, a non-electrophilic
      reference agonist of the TrpA1 channel.
AB  - TrpA1 is an ion channel involved in nociceptive and inflammatory pain. It is
      implicated in the detection of chemical irritants through covalent binding to a
      cysteine-rich intracellular region of the protein. While performing an HTS of the
      Pfizer chemical collection, a class of pyrimidines emerged as a non-reactive, non
      covalently binding family of agonists of the rat and human TrpA1 channel. Given
      the issues identified with the reference agonist Mustard Oil (MO) in screening, a
      new, non-covalently binding agonist was optimized and proved to be a superior
      agent to MO for screening purposes. Compound 16a (PF-4840154) is a potent,
      selective agonist of the rat and human TrpA1 channel and elicited TrpA1-mediated
      nocifensive behaviour in mouse.

PMID- 21741839
TI  - Development of substrate analogue inhibitors for the human airway trypsin-like
      protease HAT.
AB  - A series of substrate analogue inhibitors of the serine protease HAT, containing
      a 4-amidinobenzylamide moiety as the P1 residue, was prepared. The most potent
      compounds possess a basic amino acid in the d-configuration as P3 residue.
      Whereas inhibitor 4 (K(i) 13 nM) containing proline as the P2 residue completely
      lacks selectivity, incorporation of norvaline leads to a potent inhibitor (15,
      K(i) 15 nM) with improved selectivity for HAT in comparison to the coagulation
      proteases thrombin and factor Xa or the fibrinolytic plasmin. Selected inhibitors
      were able to suppress influenza virus replication in a HAT-expressing MDCK cell
      model.

PMID- 21741840
TI  - Histone ADP-ribosylation in DNA repair, replication and transcription.
AB  - Most published work on post-translational histone modifications focuses on small
      covalent alterations such as acetylation, methylation and phosphorylation. By
      contrast, fewer data are available on the modification of histones by ADP-ribose.
      Discussion of the biological significance of histone ADP-ribosylation has often
      been restricted to functions of the modifying enzymes, rather than to histones as
      ADP-ribose acceptors. In particular, the identification of specific lysine
      residues as ADP-ribose acceptor sites in histones and the identification of ADP
      ribose binding modules raise this modification to a par with acetylation,
      methylation or phosphorylation. We discuss here the functional aspects of histone
      ADP-ribosylation and its influence on DNA repair, replication and transcription.

PMID- 21741841
TI  - Muscle atrophy in muscle-specific tyrosine kinase (MuSK)-related myasthenia
      gravis.
AB  - Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibody (MuSK
      MG) is often associated with prominent facial and bulbar muscle atrophy. It
      remains unclear whether the muscle atrophy is a consequence of long-term
      corticosteroid treatment, or of the disease process per se. Herein, we report a
      steroid-naive patient with MuSK-MG who presented with severe weakness and marked
      atrophy of the facial and tongue muscles.

PMID- 21741842
TI  - miRNA response to DNA damage.
AB  - Faithful transmission of genetic material in eukaryotic cells requires not only
      accurate DNA replication and chromosome distribution but also the ability to
      sense and repair spontaneous and induced DNA damage. To maintain genomic
      integrity, cells undergo a DNA damage response using a complex network of
      signaling pathways composed of coordinate sensors, transducers and effectors in
      cell cycle arrest, apoptosis and DNA repair. Emerging evidence has suggested that
      miRNAs play a crucial role in regulation of DNA damage response. In this review,
      we discuss the recent findings on how miRNAs interact with the canonical DNA
      damage response and how miRNA expression is regulated after DNA damage.

PMID- 21741843
TI  - MRI analysis of the component-bone interface after TKA.
AB  - PURPOSE: The aim of the study is to describe and characterize the implant-bone
      interface of femoral, tibial and patellar components after TKA using magnet
      resonance imaging (MRI). SCOPE: Fifty-five patients who underwent MRI modified to
      reduce artifacts after TKA were identified retrospectively from medical records.
      This included 27 TKA with a zirconium femoral component and 28 TKA with
      conventional cobalt/chrome/molybdenum alloy component (CoCrMo). The MRIs were
      evaluated by two blinded, independent investigators and Cohen's Kappa was applied
      to determine the interobserver reliability. Excellent visibility, interobserver
      agreement and reliability was found for the interface of the tibial components,
      patellar buttons, and for femoral components made of zirconium. Conventional
      CoCrMo components caused significant artifact that interfered with the evaluation
      of the interface of femoral components. CONCLUSION: MRI performed with a special
      protocol allows good reproducibility of analysis of implant-bone interface at
      tibia and patella after TKA. The femoral interface was visualized for components
      made of zirconium. Conventional CoCrMo femoral components caused considerable
      artifact and interfered with the evaluation of the femoral interface. MRI
      tailored to reduce metallic susceptibility artifact can be a helpful tool for
      evaluation of prosthesis bone interface and may be helpful for the diagnosis of
      component loosening.

PMID- 21741844
TI  - Periprosthetic fractures in the distal femur following total knee replacement: A
      review and guide to management.
AB  - The management of distal femoral fractures following a total knee replacement can
      be complex and requires the equipment, perioperative support and surgical skills
      of both trauma and revision arthroplasty services. Recent advances in implant
      technology have changed the management options of these difficult fractures. This
      article describes the options available and discusses the latest evidence.

PMID- 21741845
TI  - A bright approach to the immunoproteasome: development of LMP2/beta1i-specific
      imaging probes.
AB  - While the constitutive, 26S proteasome plays an important role in regulating many
      important cellular processes, a variant form known as the immunoproteasome is
      thought to primarily function in adaptive immune responses. However, recent
      studies indicate an association of immunoproteasomes with many physiological
      disorders such as cancer, neurodegenerative, and inflammatory diseases. Despite
      this, the detailed functions of the immunoproteasome remain poorly understood.
      Immunoproteasome-specific probes are essential to gain insight into
      immunoproteasome function. Here, we describe for the first time the development
      of cell-permeable activity-based fluorescent probes, UK101-Fluor and UK101-B660,
      which selectively target the catalytically active LMP2/beta1i subunit of the
      immunoproteasome. These probes facilitate rapid detection of the cellular
      localization of catalytically active immunoproteasomes in living cells, providing
      a valuable tool to analyze immunoproteasome functions. Additionally, as
      LMP2/beta1i may serve as a potential tumor biomarker, an LMP2/beta1i-targeting
      fluorescent imaging probe may be applicable to a rapid readout assay to determine
      tumor LMP2/beta1i levels.

PMID- 21741846
TI  - Fragmental modeling of hPepT2 and analysis of its binding features by docking
      studies and pharmacophore mapping.
AB  - Over the last years, considerable progress has been made for the identification
      and characterization of drug transporters, and several modeling studies have been
      undertaken to predict their effects on ADME profiling. Thus, this study was
      focused on the peptide transporter hPepT2, which influences the regional
      pharmacokinetics in brain, the reabsorption from renal tubular fluid and the
      pulmonary delivery. A reliable model for hPepT2 was generated by fragments based
      on the resolved structure of the homologue lactose permease LacY and the
      structure is made available as Supplementary data. The interaction capacities of
      such a model were explored by docking a set of 75 known ligands. Docking results
      underlined the predilection of hPepT2 for highly hydrophobic ligands and the key
      role of ionic interactions elicited by both charged termini. The docking results
      were further verified developing a pharmacophore model which clarified the key
      features required for an optimal hPepT2 affinity and confirmed the main factors
      governing the hPepT2/hPepT1 selectivity. The soundness of the docking results and
      the agreement with the pharmacophore mapping afford an encouraging validation for
      the proposed hPepT2 model and suggest that it can be conveniently exploited to
      design peptide-like molecules with an improved affinity for this transporter.

PMID- 21741847
TI  - Discovery of potent, selective, and orally bioavailable quinoline-based
      dipeptidyl peptidase IV inhibitors targeting Lys554.
AB  - Dipeptidyl peptidase IV (DPP-4) inhibition is a validated therapeutic option for
      type 2 diabetes, exhibiting multiple antidiabetic effects with little or no risk
      of hypoglycemia. In our studies involving non-covalent DPP-4 inhibitors, a novel
      series of quinoline-based inhibitors were designed based on the co-crystal
      structure of isoquinolone 2 in complex with DPP-4 to target the side chain of
      Lys554. Synthesis and evaluation of designed compounds revealed 1-[3
      (aminomethyl)-4-(4-methylphenyl)-2-(2-methylpropyl)quinolin-6-yl]piperazine-2,5
      dione (1) as a potent, selective, and orally active DPP-4 inhibitor (IC50=1.3 nM)
      with long-lasting ex vivo activity in dogs and excellent antihyperglycemic
      effects in rats. A docking study of compound 1 revealed a hydrogen-bonding
      interaction with the side chain of Lys554, suggesting this residue as a potential
      target site useful for enhancing DPP-4 inhibition.

PMID- 21741848
TI  - Design, synthesis and evaluation of N-benzoylindazole derivatives and analogues
      as inhibitors of human neutrophil elastase.
AB  - Human neutrophil elastase (HNE) plays an important role in tumour invasion and
      inflammation. A series of N-benzoylindazoles was synthesized and evaluated for
      their ability to inhibit HNE. We found that this scaffold is appropriate for HNE
      inhibitors and that the benzoyl fragment at position 1 is essential for activity.
      The most active compounds inhibited HNE activity with IC50 values in the
      submicromolar range. Furthermore, docking studies indicated that the geometry of
      an inhibitor within the binding site and energetics of Michaelis complex
      formation were key factors influencing the inhibitor's biological activity. Thus,
      N-benzoylindazole derivatives and their analogs represent novel structural
      templates that can be utilized for further development of efficacious HNE
      inhibitors.

PMID- 21741849
TI  - Analysis of ancient Indian silver punch-marked coins by external PIXE.
AB  - Seven silver punch-marked coins were analysed using external particle induced X
      ray emission technique. The main group of elements like Ag, Cu, Au, Pb and Fe
      were estimated along with a number of trace/minor elements such as K, Ca, Ti, V,
      Cr, Mn, Co, Ni and Rb in the analysed silver coins. Gold was found in all the
      coins and varied between 0.7% and 6.2% indicating the better economic condition
      of that civilisation.

PMID- 21741850
TI  - Improved detection and measurement of low levels of [18F]fluoride metabolized
      from [18F]-labeled pyrimidine nucleoside analogues in biological samples.
AB  - INTRODUCTION: It is important to identify all circulating metabolites, including
      free fluoride, for accurate pharmacokinetic modeling of [(18)F]-labeled
      radiotracers. We sought to determine the most efficient method to detect and
      quantify low levels of free [(18)F]fluoride in biological samples. METHODS: Low
      levels of [(18)F]fluoride were analyzed using two methods: (A) an ion-exchange
      cartridge and gamma counting, and (B) radio-HPLC, to compare the detection limits
      of these two analytical methods. Twenty microliters of [(18)F]fluoride solution
      was loaded onto an ion-exchange cartridge, then eluted with 20% MeCN/water (5 ml)
      and radioactivity trapped in the cartridge counted on a gamma counter.
      [(18)F]Fluoride was also determined in plasma and urine from mice injected with
      [(18)F]-labeled thymidine analogues using Method A. RESULTS: The detection
      sensitivity of Method A was 9.4-fold higher than that of Method B (0.075+/-0.004
      vs. 0.71+/-0.02 nCi). With Method A, [(18)F]fluoride was determined in plasma for
      [(18)F]FLT, [(18)F]FMAU, [(18)F]FEAU and N(3)-[(18)F]FPrT as 1.4+/-0.31% (n=4),
      0.17+/-0.49% (n=3), 4.88+/-1.62% (n=3) and 12.94+/-0.48% (n=4), respectively. The
      amount of [(18)F]fluoride determined in the urine was 11.49+/-1.60% (n=4) from
      [(18)F]FLT, 5.36+/-2.34% (n=3) from [(18)F]FMAU, 13.57+/-1.96% (n=3) from
      [(18)F]FEAU and 11.19+/-1.98% (n=4) from N(3)-[(18)F]FPrT. CONCLUSION: Low levels
      of [(18)F]fluoride in biological samples can be detected and quantified using an
      ion-exchange cartridge and gamma counting. This methodology is simple, accurate
      and superior to the standard use of radio-HPLC on a C(18) column for metabolite
      analysis, and it should be useful in pharmacokinetic modeling for animal imaging
      studies using an [(18)F]-labeled radiotracer and PET.

PMID- 21741851
TI  - Transcripts of soybean isoflavone 7-O-glucosyltransferase and hydroxyisoflavanone
      dehydratase gene homologues are at least as abundant as transcripts of their well
      known counterparts.
AB  - The enzymes of the isoflavonoid pathway produce isoflavones, which have multiple
      functions in defence and symbiosis. Recently, we identified known and novel
      homologues of several of these enzymes in the soybean genome sequence. In the
      present study, we have investigated the transcript levels of the isoflavone 7-O
      glucosyltransferase (GmIF7GT) and 2-hydroxyisoflavanone dehydratase (HIDH) gene
      homologues in soybean seedling organs (shoot tips, unifoliate leaves, unifoliate
      nodes, epicotyls, cotyledons, cotyledonary nodes, hypocotyls and roots) as well
      as flowers, seeds and whole pods using real-time reverse-transcription polymerase
      chain reaction (real-time RT-PCR). In addition, the transcript levels were also
      measured in three cell layers of the soybean pod (exocarp, mesocarp and endocarp)
      dissected using laser capture microdissection (LCM) at two different
      developmental stages. Statistical analysis has shown that the transcript level of
      a less known gene homologue of isoflavone 7-O-glucosyltransferase (GmIF7GT4) is
      significantly higher (about 11-fold) in the roots than the well known gene
      homologue (GmIF7GT1) and the other less known homologues. It was also shown that
      the transcript levels of the less known gene homologue of 2-hydroxyisoflavanone
      dehydratase (HIDH2) do not differ from those of the well known homologue (HIDH1).

PMID- 21741852
TI  - Complications in helmet therapy.
AB  - OBJECTIVE: Helmet therapy is an established method to correct positional head
      deformity in early infancy. Side effects such as skin erythema or pressure sores
      are well known for helmet therapy, but not yet adequately discussed in current
      literature. PATIENTS AND METHODS: Retrospectively, all patient-sheets of infants
      treated by individual orthotic therapy in the years 2007 and 2008 were sighted
      and complications were noted. Complications were classified and sorted by their
      frequency and descriptive statistics was performed. The treatment to cure
      complications was recorded and success in complication control was analysed.
      RESULTS: Altogether, 410 patients fit the inclusion criteria for this
      investigation. Complications were apportioned into pressure sores, local ethanol
      erythema, unsatisfying fit of the helmet or loss of the helmet, skin infection,
      failed correction of head deformity, and subcutaneous abscess in one case. Non
      compliance is to be noticed in a high number, but mainly occurred towards the end
      of the treatment period. CONCLUSION: Helmet therapy represents a safe therapeutic
      tool for the correction of positional cranial deformity. Complications have to be
      clear in number and severity for parental elucidation. Most complications can
      easily be avoided or eliminated by proper instruction of the parents.

PMID- 21741853
TI  - Fetal trans-apical stent delivery into the pulmonary artery: prospects for
      prenatal heart-valve implantation.
AB  - OBJECTIVE: The purpose of this study was to assess the technical feasibility of a
      fetal trans-apical stent delivery into the pulmonary artery using a novel hybrid
      intervention technique as a possible route for prenatal minimally invasive heart
      valve-implantation approaches. METHODS: Pregnant Pre-Alp sheep between 122 and
      128 days' gestation (n = 3) underwent a midline laparotomy. The fetus was left in
      utero or partially externalized and its chest was opened via a left-sided
      minithoracotomy. The fetal heart was cannulated and a guide wire was introduced
      through the ductus arteriosus into the aorta. A 14-French delivery system was
      then mounted onto the guide wire and advanced to the landing zone in the
      pulmonary artery, where the stent was deployed. The position of the stent was
      confirmed using echocardiography, angiography as well as computed tomography.
      RESULTS: The trans-apical implantation was successful in all animals. However, at
      necropsy in one animal, the stent was found to partly occlude one of the
      pulmonary valvular leaflets. Bleeding at the antero-apical incision occurred in
      all animals but could be managed without fetal demise. No fetal cardiopulmonary
      bypass was performed. In all animals, contrast angiography displayed normal
      perfusion of the pulmonary vasculature as well as the ductus arteriosus.
      CONCLUSIONS: Our study demonstrates the principal technical feasibility of a
      prenatal stent delivery into the pulmonary artery using a novel trans-apical
      hybrid-intervention technique. This approach demonstrates the first step towards
      possible future minimally invasive prenatal heart-valve-implantation procedures.

PMID- 21741854
TI  - Short-term results of retrograde pulmonary embolectomy in massive and submassive
      pulmonary embolism: a single-center study of 30 patients.
AB  - OBJECTIVE: Surgical pulmonary embolectomy is usually reserved for critically ill
      patients with pulmonary embolism. The conventional antegrade technique of
      embolectomy may miss peripheral clots, rendering the patient amenable to
      developing pulmonary hypertension. Here, we present our experience with a new
      retrograde pulmonary embolectomy supplementing the current antegrade technique.
      METHODS: From January 2004 through December 2010, 30 consecutive patients
      underwent pulmonary embolectomy in our center. The study included 15 men and 15
      women whose age ranged from 28 to 80 years, with mean age of 58+/-15 years. All
      the patients except one were taken to the operating room with at least one
      imaging modality confirming the presence of a large thrombus in pulmonary
      arterial vasculature. RESULTS: The most common presenting symptoms of patients
      was dyspnea (n=27, 90%). The major indications for surgery were severe
      hemodynamic or respiratory compromise (n=11, 36%). After performing antegrade
      embolectomy, retrograde flushing of the pulmonary veins was done. The in-hospital
      mortality in our study was 6.6% (2/30). Mean intubation time for the patients was
      52.7+/-36.5 h, with a range of 12-120 h. Mean intensive care unit (ICU) admission
      for the patients was 7 days with a range of 2-60 days. CONCLUSIONS: As far as we
      know, this is the largest series of cases published so far regarding the
      immediate results of retrograde pulmonary embolectomy. This technique can
      successfully dislodge the remaining clots in distal pulmonary vasculature not
      directly visualized. Surgical pulmonary embolectomy is a safe method and should
      not be used as a last resort for patients with pulmonary embolism.

PMID- 21741855
TI  - End-of-life care across Southern Europe: a critical review of cultural
      similarities and differences between Italy, Spain and Portugal.
AB  - Evidence from a range of sources demonstrates that end-of-life (EoL) care
      practices and preferences vary across countries; culture is consistently one of
      the main explanations given for this. In order to understand how cultural factors
      are used to explain similarities and differences in EoL care between Spain, Italy
      and Portugal, database and hand searches were performed and cross-cutting core
      themes identified. Similarities included higher proportions of people who wished
      to die at home than actually died at home, a persistent trend for partial
      disclosure in Italy and Spain, low use of advance directives, and low incidence
      of all medical EoL decisions (with the exception of terminal sedation) compared
      to northern European countries. The role of religion and the importance of family
      ties were the two main cultural factors used to explain the similarities. Further
      research is needed in order to interpret the important differences that were also
      found.

PMID- 21741856
TI  - Endovascular treatment of visceral and renal artery aneurysms.
AB  - PURPOSE: To analyze early and midterm results of endovascular treatment of
      visceral aneurysms regarding technical considerations, technical success rate,
      aneurysm rupture, and end-organ ischemia. MATERIALS AND METHODS: Endovascular
      treatment of 41 visceral and renal artery aneurysms (VAAs) in 40 consecutive
      patients (25 women; mean age, 59.4 y +/- 16.2) was retrospectively reviewed. The
      series included 30 true aneurysms and 11 pseudoaneurysms in renal (n = 17),
      splenic (n = 13), hepatic (n = 4), celiac (n = 4), gastroduodenal (n = 2), and
      middle colic (n = 1) arteries. Demographic, clinical, procedural, and follow-up
      data were analyzed. RESULTS: Forty-one aneurysms underwent endovascular
      treatment. Hypertension (73%) and hyperlipidemia (32%) were the most common
      associated comorbidities. Nineteen patients presented with symptoms of pain (15%)
      or rupture (32%) in 10 pseudoaneurysms (91%) and nine true aneurysms (30%; P =
      .0007). The most commonly used technique (93%) was coil embolization with (15%)
      or without (78%) other endovascular agents. The rate of technical success
      (cessation of hemorrhage or blood flow into aneurysm sac) was 98%. There was no
      periprocedural mortality. Mean hospital stays were 1 and 2 days for asymptomatic
      and symptomatic patients, respectively. Mean clinical follow-up was 44.5 months;
      mean imaging follow-up was 11.7 months. The only complication was an
      intraprocedural thromboembolic event in one case (3%). Follow-up imaging evidence
      of end-organ partial infarct was detected in six patients (21%), with no clinical
      evidence of organ insufficiency. CONCLUSIONS: Endovascular treatment of VAAs is a
      safe and highly successful procedure. Associated side effects such as distal
      embolization and end-organ infarcts were not found to be clinically significant.

PMID- 21741857
TI  - Differences among total and in vitro digestible phosphorus content of plant foods
      and beverages.
AB  - OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important
      sources of phosphorus (P). Current data on P content and absorbability of P from
      these foods are lacking. Measurement of in vitro digestible P (DP) content of
      foods may reflect absorbability of P. The objective of this study was to measure
      both total phosphorus (TP) and DP contents of selected foods and to compare the
      amounts of TP and DP and the proportion of DP to TP among different foods.
      METHODS: TP and DP content of 21 foods and drinks of plant origin were measured
      by inductively coupled plasma optical emission spectrometry. In DP analysis,
      samples were digested enzymatically in principle in the same way as in the
      alimentary canal before P analyses. The most popular national brands were chosen
      for analysis. RESULTS: The highest amount of TP (667 mg/100 g) was found in
      sesame seeds with hull, which also had the lowest percentage of DP (6%) to TP.
      Instead, in cola drinks and beer, the percentage of DP to TP was 87 to 100% (13
      to 22 mg/100 g). In cereal products, the highest TP content (216 mg/100 g) and DP
      proportion (100%) were present in industrial muffins, which contain sodium
      phosphate as a leavening agent. Legumes contained an average DP content of 83
      mg/100 g (38% of TP). CONCLUSION: Absorbability of P may differ substantially
      among different plant foods. Despite high TP content, legumes may be a relatively
      poor P source. In foods containing phosphate additives, the proportion of DP is
      high, which supports previous conclusions of the effective absorbability of P
      from P additives.

PMID- 21741858
TI  - The rs7204609 polymorphism in the fat mass and obesity-associated gene is
      positively associated with central obesity and microalbuminuria in patients with
      type 2 diabetes from Southern Brazil.
AB  - OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the fat mass and obesity
      associated (FTO) gene, especially the common rs9939609 (A/T) SNP, are associated
      with body mass index (BMI), diabetes, and metabolic syndrome (MetS). MetS is
      highly prevalent in patients with type 2 diabetes and has been associated with
      chronic diabetic complications. Therefore, the aim of this study was to evaluate
      possible associations of the scarcely investigated rs7204609 (C/T) polymorphism,
      as well as the rs9939609 (A/T) polymorphism, with MetS and chronic diabetic
      complications in type 2 diabetic patients from Southern Brazil. DESIGN: This was
      a cross-sectional study. PATIENTS AND METHODS: A total of 236 patients with type
      2 diabetes (age: 60.0 +/- 10.3 years; diabetes duration: 12.7 +/- 8.2 years;
      53.4% women) were genotyped for the FTO rs7204609 and rs9939609 polymorphisms
      (ABI PRISM 7000 Real-Time PCR System). Patients underwent clinical, laboratory,
      and nutritional evaluation. MetS was defined according to the 2009-Joint Interim
      Statement. RESULTS: Carriers of C allele of the rs7204609 polymorphism (CT/CC
      genotypes, n = 35) were at increased risk for the presence of MetS (odds ratio
      [OR] = 4.56; 95% CI: 1.04 to 19.9), elevated waist circumference (OR = 8.66; 95%
      CI: 1.12 to 66.7), BMI: >= 30 kg/m(2) (OR = 3.71; 95% CI: 1.71 to 8.02), and
      microalbuminuria (OR = 2.30; 95% CI: 1.08 to 4.88), adjusted for gender and
      diabetes duration (P < .05 for all models). The rs9939609 polymorphism was not
      associated with MetS, elevated waist circumference or BMI, or diabetic
      complications. Daily energy and nutrient intakes did not differ according to the
      presence of the polymorphisms. CONCLUSIONS: The C allele of the rs7204609
      polymorphism in the FTO gene increased the chance for the presence of MetS,
      especially central obesity, and microalbuminuria, independently of energy and
      nutrient intakes in this sample of type 2 diabetic patients from Southern Brazil.

PMID- 21741859
TI  - Association between circulating electronegative low-density lipoproteins and
      serum ferritin in hemodialysis patients: a pilot study.
AB  - BACKGROUND: Iron supplementation is a common recommendation to chronic kidney
      disease patients undergoing hemodialysis (HD). However, iron excess is closely
      associated with lipid peroxidation and, it is well known that electronegative low
      density lipoproteins (LDL[-]) are present at higher plasma concentrations in
      diseases with high cardiovascular risk such as chronic kidney disease. Thus, the
      aim of this study was to investigate whether ferritin levels are associated with
      LDL(-) levels in HD patients. DESIGN: This was a cross-sectional study. SETTING:
      This study was conducted from a private clinic in Rio de Janeiro, Brazil.
      PATIENTS: The study included 27 HD patients and 15 healthy subjects. METHODS AND
      PROCEDURES: Twenty-seven HD patients (14 men, 58.6 +/- 10 years, 62.2 +/- 51.4
      months on dialysis, and body mass index: 24.4 +/- 4.2 kg/m(2)) were studied and
      compared with 15 healthy individuals (6 men, 53.8 +/- 15.4 years, body mass
      index: 24.5 +/- 4.3 kg/m(2)). Serum LDL(-) levels were measured using the enzyme
      linked immunosorbent assay method; ferritin levels by commercially available
      kits, and tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant
      protein-1, and plasminogen activator inhibitor-1 were determined with a multiplex
      assay kit manufactured by R&D Systems. RESULTS: The HD patients presented higher
      LDL(-) and tumor necrosis factor-alpha levels (0.15 +/- 0.13 U/L and 5.9 +/- 2.3
      pg/mL, respectively) than healthy subjects (0.07 +/- 0.05 U/L and 2.3 +/- 1.3
      pg/mL, respectively) (P = .0001). The mean ferritin level in HD patients was
      1,117.5 +/- 610.4 ng/mL, and 90% of patients showed ferritin levels exceeding 500
      ng/mL. We found a positive correlation between LDL(-) and ferritin in the
      patients (r = 0.48; P = .01), and ferritin was a significant contributor to LDL(
      ) concentrations independent of inflammation. CONCLUSIONS: Excess body iron
      stores for HD patients was associated with signs of increased oxidative stress,
      as reflected by increased LDL(-) levels in HD patients.

PMID- 21741860
TI  - Seasonal changes in phosphorus content of fish tissue as they relate to diets of
      renal patients.
AB  - OBJECTIVE: To investigate seasonal variations in tissue phosphorus (P) levels, P
      to protein ratio, and P to omega-3 fatty acid (omega3-FA) ratio in 2 species of
      fish that are commonly consumed in Lebanon. We aim to determine suitability for
      dietary management of renal patients. DESIGN AND SETTING: Siganus rivulatus
      (rabbitfish) and Diplodus sargus (white seabream) were caught in traps off the
      coast of Beirut and transported on ice to the laboratory during various seasons.
      Fillets of fish were removed, dried to constant weight at 95 degrees C, finely
      ground, and stored at -20 degrees C. Protein, P, P to protein ratio, and P to
      omega3-FA ratio were determined. RESULTS: Compared with white seabream
      (carnivore), rabbitfish (algaevore) had a significantly lower mean P content (+/
      SE) (895 +/- 32 mg/100 g vs. 1,132 +/- 23 mg/100 g; P < .0001), a significantly
      lower P to protein ratio (+/-SE) (10.35 +/- 0.39 vs. 13.15 +/- 0.34 mg P/g of
      protein; P < .001), and a significantly lower P to omega3-FA ratio (+/-SE) (2.81
      +/- 0.29 vs. 5.93 +/- 1.05 g of omega3-FA/g of P; P < .005). P content in flesh
      of both species varied significantly with season (P < .0001). Rabbitfish P
      content was least in August and greatest in June (P < .05), whereas white
      seabream P content was greatest in April and least in June (P < .05). Rabbitfish
      muscle P to protein ratio and P to omega3-FA ratio was least in August, with a
      significantly greater P to omega3-FA ratio during the rest of the year. White
      seabream exhibited wider seasonal variation in P to protein ratio and P to omega3
      FA ratio as compared with rabbitfish. CONCLUSION: Because of differences and
      seasonal variations in P levels that exist among fish species, renal dietitians
      may need to identify the seasonal proximate composition of individual fish
      species in various habitats and formulate dietary regimens accordingly. Such
      advice notwithstanding, oily marine fish remain a healthy food choice for
      dialysis patients if the fillet is consumed without bones.

PMID- 21741861
TI  - Deep vein thrombosis after bunionectomy: a case report of two genetic mutations.
AB  - Deep venous thrombosis after foot and ankle surgery is a serious complication
      that can have potentially life-threatening complications, such as pulmonary
      embolus. Genetic mutations have been reported in the published data to cause an
      increased risk of developing deep vein thrombosis. Two such genetic mutations are
      the methylenetetrahydrofolate reductase gene variant C677T and the 4G/5G
      polymorphism of the plasminogen activator inhibitor gene. This case report
      presents a female patient who developed a postoperative deep vein thrombosis
      after hallux valgus reconstruction. A hypercoagulable panel revealed the 2
      mentioned genetic mutations. We hope this case study will highlight the
      importance of ascertaining all patient risk factors and the relation to
      perioperative deep vein thrombosis prophylaxis.

PMID- 21741862
TI  - Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of
      prostate cancer and tumor aggressiveness.
AB  - The human tissue Kallikrein family consists of 15 genes with the majority shown
      to be differentially expressed in cancers and/or indicators of cancer prognosis.
      We sought to elucidate the role of common genetic variation in four of the
      Kallikrein genes, KLK5, KLK6, KLK12, and KLK13, in prostate cancer risk and tumor
      aggressiveness. Genotyping of all 22 tagging single nucleotide polymorphisms
      (tagSNPs) in the KLK5, KLK6, KLK12, and KLK13 genes was performed in
      approximately 1,000 prostate cancer cases and 1,300 male controls from Australia.
      Data from any positive results were also accessed for 1,844 cases and 1,886
      controls from a previously published prostate cancer genome-wide association
      study set from the United Kingdom. For one SNP in KLK12, rs3865443, there was
      evidence for association with prostate cancer risk of similar direction and
      magnitude in the replication set to that seen in the Australian cohort. We
      conducted genotyping of a further 309 prostate cancer cases, and combined
      analyses revealed an increased risk of prostate cancer for carriers of the rare
      homozygous genotype for rs3865443 (OR 1.28, 95% CI 1.04-1.57; P = 0.018). No
      other tagSNPs in the KLK5, KLK6, and KLK13 genes were consistently associated
      with prostate cancer risk or tumor aggressiveness. Analysis of a combined sample
      of 3,153 cases and 3,199 controls revealed the KLK12 tagSNP rs3865443 to be
      marginally statistically significantly associated with risk of prostate cancer.
      Considering the total number of SNPs investigated in this study, this finding
      should be interpreted cautiously and requires additional validation from very
      large datasets such as those of the Prostate Cancer Association group to
      investigate cancer associated alterations (PRACTICAL) Consortium.

PMID- 21741863
TI  - Clinical evaluation of an end-tidal target-controlled infusion closed-loop system
      for isoflurane administration in horses undergoing surgical procedures.
AB  - A new volatile anaesthetic agent delivery system was tested in 15 horses
      undergoing scheduled surgical procedures. The delivery system consisted of a
      laptop computer (with dedicated software), a computer-controlled syringe driver
      (loaded with liquid isoflurane) connected to the inspiratory arm of a large
      animal circle breathing system and a respiratory gas monitor, providing
      isoflurane end-tidal concentrations (ET(measured)) every 20 s to the computer.
      Following induction and connection to the breathing system, mechanical
      ventilation was started. The bodyweight (BW), fresh gas flow, breathing system
      and ventilator volume, and end-tidal isoflurane target (ET(target)) were entered
      into the computer. Using Lowe's equation, the software calculated the prime dose
      to be delivered by the syringe driver over 2 min. After this, the system
      delivered each minute the amount of isoflurane as determined by the following
      equation: Isoflurane (mL) = {2 * lambda(B/G) * (200 * BW(0.75)) * (ET(target) -
      ET(measured)) + (fresh gas flow - (BW(0.75) * 0.07)) * (ET(measured))}/206. A
      fresh gas flow of 4 L oxygen min(-1) was administered until the inspired fraction
      of oxygen reached 0.7, and was then decreased. A target of 1.5% end-tidal
      isoflurane was initially used and subsequently adjusted to the clinical
      requirements. The system performance was evaluated using the median prediction
      error (MDPE) and the median absolute performance error (MDAPE), which were -3.6%
      and 5.29%, respectively. It was concluded that this system was useful to achieve
      end-tidal target-controlled infusion of isoflurane during equine anaesthesia.

PMID- 21741864
TI  - An evaluation of the effect of clotting on the recovery of copper from caprine
      blood.
AB  - In the goat, diagnosis of copper (Cu) deficiency is often based on measurement of
      Cu in serum or plasma. Previous research in cattle and sheep has shown that these
      values are not interchangeable, but data for goats have not been published.
      Paired serum and heparinised plasma samples taken from 119 goats in eight herds
      were tested for Cu concentration. Plasma and serum Cu were significantly
      correlated (r=0.95). On average serum Cu was 3.5 MUmol/L lower than plasma Cu,
      but this difference was related to Cu status (r=0.45). Mean serum Cu
      concentration was 83% of plasma Cu, with the 95% limits of agreement ranging from
      66% to 100%. Similar to cattle and sheep, individual variability in Cu loss
      during clotting is too great for serum Cu to be used as a measure of Cu status in
      goats.

PMID- 21741865
TI  - How the Orthopedic Foundation for Animals (OFA) is tackling inherited disorders
      in the USA: using hip and elbow dysplasia as examples.
AB  - The Orthopedic Foundation for Animals (OFA) maintains an on-line health pedigree
      database for inherited disorders of animals. With the American Kennel Club Canine
      Health Foundation, the OFA maintains the Canine Health Information Center (CHIC)
      for parent breed clubs to identify breed-specific required health tests. Analysis
      of the results of OFA evaluations in the hip and elbow registries show that
      selection based on phenotype improves conformation. Disorders with complex
      inheritance respond best to selection based on depth (ancestors) and breadth
      (siblings) of pedigree health test results. This information can be derived from
      vertical pedigrees generated on the OFA website.

PMID- 21741866
TI  - International and collaborative strategies to enhance genetic health in purebred
      dogs.
AB  - Health problems in pedigree dogs have recently been highlighted in the media
      worldwide and verified internationally by cynological organisations.
      Collaborative actions are now needed to deal with both existing and future
      issues. In this article, potential roles for various stakeholders are discussed
      and the value of national and international platforms for collaborations is
      stressed. Development of specific strategies for action must be based on criteria
      of significance, such as severity, prevalence and inheritance, as well as
      availability of effective preventive measures. Assessment of options should be
      founded on evidence from appropriate populations-at-risk and consider broader
      issues, such as demographics and human-animal interactions. Existing data, such
      as those from insurance statistics and health surveys, should be used as a
      reference until representative national/international population-level breed
      specific data are available. Key issues and challenges, as well as possible
      strategies to address them, are discussed.

PMID- 21741868
TI  - Detection of undistorted continuous wave (CW) electron paramagnetic resonance
      (EPR) spectra with non-adiabatic rapid sweep (NARS) of the magnetic field.
AB  - A continuous wave (CW) electron paramagnetic resonance (EPR) spectrum is
      typically displayed as the first harmonic response to the application of 100 kHz
      magnetic field modulation, which is used to enhance sensitivity by reducing the
      level of 1/f noise. However, magnetic field modulation of any amplitude causes
      spectral broadening and sacrifices EPR spectral intensity by at least a factor of
      two. In the work presented here, a CW rapid-scan spectroscopic technique that
      avoids these compromises and also provides a means of avoiding 1/f noise is
      developed. This technique, termed non-adiabatic rapid sweep (NARS) EPR, consists
      of repetitively sweeping the polarizing magnetic field in a linear manner over a
      spectral fragment with a small coil at a repetition rate that is sufficiently
      high that receiver noise, microwave phase noise, and environmental microphonics,
      each of which has 1/f characteristics, are overcome. Nevertheless, the rate of
      sweep is sufficiently slow that adiabatic responses are avoided and the spin
      system is always close to thermal equilibrium. The repetitively acquired spectra
      from the spectral fragment are averaged. Under these conditions, undistorted pure
      absorption spectra are obtained without broadening or loss of signal intensity. A
      digital filter such as a moving average is applied to remove high frequency
      noise, which is approximately equivalent in bandwidth to use of an integrating
      time constant in conventional field modulation with lock-in detection. Nitroxide
      spectra at L- and X-band are presented.

PMID- 21741869
TI  - Monitoring mass transport in heterogeneously catalyzed reactions by field
      gradient NMR for assessing reaction efficiency in a single pellet.
AB  - An important aspect in assessing the performance of a catalytically active
      reactor is the accessibility of the reactive sites inside the individual pellets,
      and the mass transfer of reactants and products to and from these sites. Optimal
      design often requires a suitable combination of micro- and macropores in order to
      facilitate mass transport inside the pellet. In an exothermic reaction, fluid
      exchange between the pellet and the surrounding medium is enhanced by convection,
      and often by the occurrence of gas bubbles. Determining mass flow in the vicinity
      of a pellet thus represents a parameter for quantifying the reaction efficiency
      and its dependence on time or external reaction conditions. Field gradient
      Nuclear Magnetic Resonance (NMR) methods are suggested as a tool for providing
      parameters sensitive to this mass flow in a contact-free and non-invasive way.
      For the example of bubble-forming hydrogen peroxide decomposition in an alumina
      pellet, the dependence of the mean-squared displacement of fluid molecules on
      spatial direction, observation time and reaction time is presented, and multi
      pulse techniques are employed in order to separate molecular displacements from
      coherent and incoherent motion on the timescale of the experiment. The reaction
      progress is followed until the complete decomposition of H2O2.

PMID- 21741870
TI  - Impact of miscentering on patient dose and image noise in x-ray CT imaging:
      phantom and clinical studies.
AB  - The operation of the bowtie filter in x-ray CT is correct if the object being
      scanned is properly centered in the scanner's field-of-view. Otherwise, the dose
      delivered to the patient and image noise will deviate from optimal setting. We
      investigate the effect of miscentering on image noise and surface dose on three
      commercial CT scanners. Six cylindrical phantoms with different size and material
      were scanned on each scanner. The phantoms were positioned at 0, 2, 4 and 6 cm
      below the isocenter of the scanner's field-of-view. Regression models of surface
      dose and noise were produced as a function of miscentering magnitude and
      phantom's size. 480 patients were assessed using the calculated regression models
      to estimate the influence of patient miscentering on image noise and patient
      surface dose in seven imaging centers. For the 64-slice CT scanner, the maximum
      increase of surface dose using the CTDI-32 phantom was 13.5%, 33.3% and 51.1% for
      miscenterings of 2, 4 and 6 cm, respectively. The analysis of patients' scout
      scans showed miscentering of 2.2 cm in average below the isocenter. An average
      increase of 23% and 7% was observed for patient dose and image noise,
      respectively. The maximum variation in patient miscentering derived from the
      comparison of imaging centers using the same scanner was 1.6 cm. Patient
      miscentering may substantially increase surface dose and image noise. Therefore,
      technologists are strongly encouraged to pay greater attention to patient
      centering.

PMID- 21741871
TI  - [Pharmacogenetics and the hospital pharmacy].

PMID- 21741872
TI  - Inter- and intra-observer variation in soft-tissue sarcoma target definition.
AB  - PURPOSE: To evaluate inter- and intra-observer variability in gross tumor volume
      definition for adult limb/trunk soft tissue sarcomas. PATIENTS AND METHODS:
      Imaging studies of 15 patients previously treated with preoperative radiation
      were used in this study. Five physicians (radiation oncologists, orthopedic
      surgeons and a musculoskeletal radiologist) were asked to contour each of the 15
      tumors on T1-weighted, gadolinium-enhanced magnetic resonance images. These
      contours were drawn twice by each physician. The volume and center of mass
      coordinates for each gross tumor volume were extracted and a Boolean analysis was
      performed to measure the degree of volume overlap. RESULTS: The median standard
      deviation in gross tumor volumes across observers was 6.1% of the average volume
      (range: 1.8%-24.9%). There was remarkably little variation in the 3D position of
      the gross tumor volume center of mass. For the 15 patients, the standard
      deviation of the 3D distance between centers of mass ranged from 0.06 mm to 1.7
      mm (median 0.1mm). Boolean analysis demonstrated that 53% to 90% of the gross
      tumor volume was common to all observers (median overlap: 79%). The standard
      deviation in gross tumor volumes on repeat contouring was 4.8% (range: 0.1-14.4%)
      with a standard deviation change in the position of the center of mass of 0.4mm
      (range: 0mm-2.6mm) and a median overlap of 93% (range: 73%-98%). CONCLUSION:
      Although significant inter-observer differences were seen in gross tumor volume
      definition of adult soft-tissue sarcoma, the center of mass of these volumes was
      remarkably consistent. Variations in volume definition did not correlate with
      tumor size. Radiation oncologists should not hesitate to review their contours
      with a colleague (surgeon, radiologist or fellow radiation oncologist) to ensure
      that they are not outliers in sarcoma gross tumor volume definition. Protocols
      should take into account variations in volume definition when considering tighter
      clinical target volumes.

PMID- 21741873
TI  - The kinetics and mechanism of ultrasonic degradation of p-nitrophenol in aqueous
      solution with CCl4 enhancement.
AB  - The ultrasonic degradation of p-nitrophenol (p-NP) in aqueous solution with CCl4
      enhancement was studied. The effects of operating parameters such as CCl4 dosage,
      ultrasonic power, media temperature, the initial concentration of p-NP and
      initial pH value of the aqueous solution on the degradation of p-NP were
      investigated, and the enhancement mechanism of CCl4 for p-NP sonolysis was also
      discussed. The results showed that the sonochemical degradation of p-NP was
      obviously enhanced by adding CCl4. It attributed to the increase .OH radicals
      concentration in the presence of CCl4 as a hydrogen atom scavenger, and the
      formation of some oxidizing agents such as free chlorine and chlorine-containing
      radicals. The degradation of p-NP follows a pseudo-first-order kinetics. The
      degradation rate of p-NP increased with decreasing the temperature, the initial
      pH value of the solution and decreasing the initial concentration of p-NP. It was
      also found that p-NP can be mineralized in this process.

PMID- 21741874
TI  - Parkinson's disease: the non-motor issues.
AB  - Non-motor symptoms (NMS) of Parkinson's disease remain the most under-appreciated
      and under-researched when taken as a whole. Data is emerging that it is the
      "totaL" burden of NMS that is the major determinant of quality of life not a
      single NMS such as depression for instance. Only recently validated tools such as
      the NMSQuest which empowers patients to declare NMS and the NMS scale, the SCOPA
      scales, and the modified version of the MDS-UPDRS have become available and
      validated for bedside clinical assessment of NMS. For the first time clinical
      trials have been incorporating non-motor measures as outcome measures and
      clinical recommendations for treatment of non-motor symptoms of PD are being
      published. This review aims to address some of these topical and "real life"
      aspects of modern day management of Parkinson's.

PMID- 21741875
TI  - Field validation of secondary commercial data sources on the retail food outlet
      environment in the U.S.
AB  - This study used direct field observations with interior assessments of outlets to
      validate food store and restaurant data from two commercial business lists
      conditional on classification of outlet type, including supermarkets, grocery
      stores, convenience stores, full-service restaurants and fast food restaurants.
      The study used a stratified random sample that included 274 urban census tracts
      across 9 counties from the Chicago Metropolitan Statistical Area (MSA) and 46
      suburban and 61 rural census tracts across 13 counties from a 50-mile buffer
      surrounding the MSA. Results showed that agreement between the field observations
      and the commercial business lists for the food store and restaurant outlets was
      generally moderate (ranging from fair to good). However, when the listed data
      were validated based on an exact classification match, agreement was only fair
      (ranging from poor to moderate) and, in particular, poor for fast food
      restaurants. The study also found that agreement levels for some outlet types
      differed by tract characteristics. Commercial databases must be used with caution
      as substitutes for on the ground data collection.

PMID- 21741876
TI  - Polymorphisms in tobacco metabolism and DNA repair genes modulate oral precancer
      and cancer risk.
AB  - The highest rates of oral squamous cell carcinomas are observed in south Asia,
      particularly in India, where complex forms of tobacco and alcohol exposures
      exist. Genetic polymorphisms contribute significantly to observed differences in
      cancer susceptibility. We examined the association of 13 variants in eight genes
      (rs4646903, rs2031920, rs3813867, GSTM1 null, GSTT1 null, rs1695, rs1138272,
      rs1799782, rs25487, rs1799791, rs1799793, rs13181 and rs1052133) involved in
      various stages of tobacco and alcohol metabolism and the risk of leukoplakia and
      oral cancer (OC) in a case-control study involving 219 oral leukoplakia, 665 OC
      and 802 age, sex and habit-matched controls. GSTT1 null and rs1695 were inversely
      associated with oral leukoplakia while GSTM1 null, GSTT1 null, rs2031920,
      rs3813867 (CYP2E1), and rs13181 were associated with OC. We report that genetic
      variants associated with premalignant and malignant conditions of the oral cavity
      differ. The associations appeared to be consistent among smokeless tobacco users,
      a characteristic risk factor in these parts.

PMID- 21741877
TI  - Ossifying fibroma of the jaws: report of two cases and literature review.
AB  - Ossifying fibromas are uncommon benign tumors of the craniofacial skeleton
      thought to originate from the periodontal ligament. Most are small and
      incidentally diagnosed with routine dental radiographs. With larger lesions,
      patients may complain of an abnormal bite or an enlarging mass. This tumor
      involves slow-evolving growth with deforming swelling generally arising in the
      mandible, with possible early tooth displacement. From the radiological
      perspective, more than 50% of the lesions exhibit an expansion of the jaws and
      53% shows well-defined unilocular radiolucencies and 40% are mixed radiolucent
      radiopaque lesions. The lesions exceptionally can be radiopaque. Ossifying
      fibroma presents several variant histopathological subtypes. The overlapping
      clinical and histopathological features of these subtypes have led to diagnostic
      dilemma and confusion. Complete excision of this tumor has become a necessity
      since it is notorious for recurrence. We present here two cases of ossifying
      fibroma of the jaws along with insight into the literature review.

PMID- 21741878
TI  - Mucosal biofilms of Candida albicans.
AB  - Biofilms are microbial communities that form on surfaces and are embedded in an
      extracellular matrix. C. albicans forms pathogenic mucosal biofilms that are
      evoked by changes in host immunity or mucosal ecology. Mucosal surfaces are
      inhabited by many microbial species; hence these biofilms are polymicrobial.
      Several recent studies have applied paradigms of biofilm analysis to study
      mucosal C. albicans infections. These studies reveal that the Bcr1 transcription
      factor is a master regulator of C. albicans biofilm formation under diverse
      conditions, though the most relevant Bcr1 target genes can vary with the biofilm
      niche. An important determinant of mucosal biofilm formation is the interaction
      with host defenses. Finally, studies of interactions between bacterial species
      and C. albicans provide insight into the communication mechanisms that endow
      polymicrobial biofilms with unique properties.

PMID- 21741879
TI  - Delimitation of the Thoracosphaeraceae (Dinophyceae), including the calcareous
      dinoflagellates, based on large amounts of ribosomal RNA sequence data.
AB  - The phylogenetic relationships of the Dinophyceae (Alveolata) are not
      sufficiently resolved at present. The Thoracosphaeraceae (Peridiniales) are the
      only group of the Alveolata that include members with calcareous coccoid stages;
      this trait is considered apomorphic. Although the coccoid stage apparently is not
      calcareous, Bysmatrum has been assigned to the Thoracosphaeraceae based on thecal
      morphology. We tested the monophyly of the Thoracosphaeraceae using large sets of
      ribosomal RNA sequence data of the Alveolata including the Dinophyceae.
      Phylogenetic analyses were performed using Maximum Likelihood and Bayesian
      approaches. The Thoracosphaeraceae were monophyletic, but included also a number
      of non-calcareous dinophytes (such as Pentapharsodinium and Pfiesteria) and even
      parasites (such as Duboscquodinium and Tintinnophagus). Bysmatrum had an isolated
      and uncertain phylogenetic position outside the Thoracosphaeraceae. The
      phylogenetic relationships among calcareous dinophytes appear complex, and the
      assumption of the single origin of the potential to produce calcareous structures
      is challenged. The application of concatenated ribosomal RNA sequence data may
      prove promising for phylogenetic reconstructions of the Dinophyceae in future.

PMID- 21741880
TI  - The role of innate immunity activation in house dust mite allergy.
AB  - House dust mite (HDM) allergy is a frequent inflammatory disease found worldwide.
      Although allergen-specific CD4(+) Th2 cells orchestrate the HDM allergic
      response, notably through induction of IgE directed towards mite allergens,
      recent studies have demonstrated that innate immunity activation also plays a
      critical role in HDM-induced allergy pathogenesis. HDM allergens can not only be
      considered proteins that induce adaptive Th2-biased responses in susceptible
      subjects but also as strong activators of innate immune cells, including skin
      keratinocytes and airway epithelial cells. The contribution of microbial adjuvant
      factors, derived from HDM carriers or the environment, is also essential in such
      cell stimulation. This review highlights how HDM allergens, together with
      microbial compounds, promote allergic responses through pattern recognition
      receptor-dependent pathways.

PMID- 21741881
TI  - Regulatory T cells in CNS injury: the simple, the complex and the confused.
AB  - Regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs) have been the focus of
      significant attention for their role in controlling immune responses. Although
      knowledge of Treg biology has burgeoned, wide gaps remain in our understanding of
      Treg function under both normal and pathological conditions. Pioneering studies
      demonstrated roles for Tregs in cancer and autoimmune diseases, including
      experimental autoimmune encephalitis, and this knowledge is often applied to
      other pathologies including neurodegenerative conditions. However, differences
      between immunity in neurodegeneration and in malignancy or autoimmunity are often
      neglected. Thus, Treg manipulations in central nervous system (CNS)
      neurodegenerative conditions often yield unexpected outcomes. In this piece, we
      explore how the immunology of neurodegeneration differs from that of cancer and
      autoimmunity and how these differences create confusion about the role of Tregs
      in neurodegenerative conditions.

PMID- 21741882
TI  - Anxiety symptoms in epilepsy: salient issues for future research.
AB  - This paper reviews the distinct symptom profile, epidemiology, pathogenesis,
      assessment, and treatment of anxiety disorders. It highlights emerging
      neuroimaging research in mood and anxiety disorders in people with epilepsy.
      While structural neuroimaging has implicated frontal temporal grey matter
      structures in mood and anxiety disorders, diffusion tensor imaging and magnetic
      resonance spectroscopy (MRS) show promise in elucidating white matter changes. In
      addition, future MRS studies may demonstrate changes in glutamate and gamma
      aminobutyric acid (GABA) levels in these regions and hopefully help inform
      response to treatment.

PMID- 21741883
TI  - Raloxifene and tibolone in elderly women: a randomized, double-blind, double
      dummy, placebo-controlled trial.
AB  - OBJECTIVES: The authors' first aim was to study the effects of raloxifene and
      tibolone on body mass density, handgrip strength, and other secondary frailty
      components. The secondary aim was to compare the effects of raloxifene and
      tibolone and their safety in older women. DESIGN/SETTING/PARTICIPANTS: A
      randomized, double-blind, double- dummy, placebo-controlled trial conducted in an
      academic hospital in the Netherlands among 318 community living women aged >70
      were randomized; 290 received the allocated intervention: 97 placebo, 101
      raloxifene, and 92 tibolone. INTERVENTIONS: Randomization was made to raloxifene
      60 mg, tibolone 1.25 mg, or placebo. Assessments were performed at baseline and
      after 3, 6, 12, and 24 months. The study was conducted from July 2003 to January
      2008. The tibolone group stopped earlier in February 2006, because of results of
      the Long-Term Intervention on Fractures with Tibolone study, suggesting an
      increased risk of cerebrovascular accident. MEASUREMENTS: Primary endpoints were
      body mass density and handgrip strength. Secondary endpoints were muscle power
      and strength, mobility measures, body composition, verbal memory, mental
      processing speed, anxiety, mood, and quality of life. RESULTS: Tibolone and
      raloxifene had similar body mass density-effect sizes (d = .24-.47), and had no
      effect on handgrip muscle strength. For the 15 words test the effect on direct
      recall of concrete and abstract words (d = .40 and d =.27, respectively) and on
      delayed recall of concrete words (d = .77) were significantly higher in the
      raloxifene group compared to placebo and to tibolone. In the raloxifene group the
      health status (EuroQol VAS (0-100) was improved 2.4 points [95% CI 0.5-4.2; P =
      .012] over 24 months. CONCLUSION: In women >70 years old, raloxifene and tibolone
      significantly and similarly increased body mass density but not muscle strength.
      Raloxifene had also positive effects on verbal memory and health status. New
      research with selective estrogen receptor modulators like raloxifene might be
      promising on frailty endpoints in elderly women. TRIAL REGISTRATION NUMBER:
      Nederlands Trial Register: 1232.

PMID- 21741884
TI  - When is a chronic wound infected?

PMID- 21741885
TI  - Vascular response to coronary artery stenting in mature and juvenile swine.
AB  - PURPOSE: The objective of this study was to investigate potential differences in
      vascular response to stenting of coronary arteries with bare metal (BMS) and drug
      eluting (DES) stents in juvenile vs. mature swine. METHODS AND MATERIALS: Twenty
      one mature (> 3 years) and 22 juvenile (6-9 months) Yucatan swine were implanted
      with 3 * 12-mm XIENCE V DES and ML VISION BMS in coronary arteries. After 7 and
      28 days, vessels were analyzed using light microscopy (n = 5-7) and confocal and
      scanning electron microscopy (n = 5-10). Messenger RNA expression levels of
      inflammatory and endothelial gene markers were tested from stented tissue at 7
      and 28 days (n = 3). A 2 * 2 analysis of variance followed by t tests compared
      treatment and/or age effects. RESULTS: No age differences in neointimal area and
      percentage stenosis were measured. Juvenile swine exhibited increased fibrin
      scores compared to mature swine (2.6 +/- 0.5 vs. 2.2 +/- 0.5, P < .05) at 7 days,
      with no age-related difference at 28 days. At 7 days, significant increases in
      para-strut inflammation (P < .01) and in VCAM-1, ICAM-1, CD40 and MCP-1 gene
      expression (P < .05) were observed in mature swine, but differences were largely
      resolved by 28 days. DES exhibited less endothelial coverage than BMS at 7 days,
      but this difference was abrogated by 28 days, with no difference between age
      groups. CONCLUSIONS: Our results indicate that mature swine exhibited an
      increased foreign body response compared to mature swine at 7 and 28 days
      following stenting that may indicate marginal delays in resolution of foreign
      body response in aged populations. These differences are unlikely to affect
      methodologies for preclinical stent safety evaluations.

PMID- 21741886
TI  - Quality of life, behavioral problems, and marital adjustment in the first year
      after radical prostatectomy.
AB  - Patients submitted for prostatectomy were evaluated regarding their quality of
      life, behavioral problems, and marital adjustment. Thirty-two patients aged 54-76
      years old were included. The results indicated that prostatectomy does not
      prevent normal psychological functioning, although there is a relationship
      between smoking and lower quality of life in these patients. INTRODUCTION:
      Different types of monotherapy for prostate cancer leads to impairment in urinary
      and sexual functions, but prostatectomy seems to have worse results in physical
      functioning when compared with other treatments. Nevertheless, patients report
      high quality of life (QOL) levels, even when there are comments about the impact
      of sexual dysfunction on psychological health. The objectives of this work were
      to analyze levels of QOL, marital adjustment (MA), and behavioral problems (BP)
      of patients submitted to prostatectomy. METHODS: Thirty-two patients from 54 to
      76 years of age who underwent radical prostatectomy were evaluated during their
      follow-up appointments with the medical staff at the urology department of a
      private medical school. QOL scores were obtained from the World Health
      Organization Quality of Life instrument, short version. BP scores of patients
      younger than 60 years of age were assessed through the Adult Self-Report, whereas
      patients older than 60 years were assessed through the Older Adult Self-Report.
      MA scores were obtained by using the Locke-Wallace Marital Adjustment Test.
      RESULTS: The patients reported relatively high levels of QOL and MA, along with
      low BPs. Marital support was associated with higher levels of QOL. BPs were
      associated with lower physical and total QOL scores. Smoking habits were
      associated with lower levels of MA, psychological health, and QOL. Erectile
      dysfunction was related to lower MA levels and lower QOL scores. CONCLUSIONS:
      Overall, the patients had high self-reported QOL levels, which indicated that
      physical impairments related to surgery did not prevent patients to return to
      normal functioning.

PMID- 21741888
TI  - Nickel response in function of temperature differences: effects at different
      levels of biological organization in Daphnia magna.
AB  - In this study, gene transcription profiling in combination with the assessment of
      systemic parameters at individual and population levels were applied to study the
      (toxic) effects induced through temperature stress in the presence or the absence
      of an additional chemical stressor (nickel) in Daphnia magna. It was illustrated
      that lower temperatures were mainly characterized by a reduction of growth and
      lipid content, while higher temperatures caused an increase of both endpoints.
      Many of the differentially regulated transcripts could be correlated with
      processes affected at higher hierarchical levels of biological organization. Gene
      clusters with probable roles in producing offspring (peak expression at 22
      degrees C), enhancing the metabolic rate (temperature related expression) and
      translational processes (increased expression at 14 degrees C) were identified.
      However, it was not possible to pinpoint a specific subset of genes, exclusively
      responding to temperature or nickel and allowing a retrospective identification
      of the particular stressor. Overall, extreme temperatures caused a higher level
      of stress in the organisms in comparison to nickel exposure. Moreover, organisms
      subjected to the natural stressor appeared to be less capable of dealing with the
      additional chemical stressor and as a result activate or repress more gene
      pathways.

PMID- 21741889
TI  - Surgical management of two complex cases of large juvenile orbital ossifying
      fibroma.
AB  - Ossifying fibroma is a rare benign tumour of the craniofacial skeleton, which can
      have an aggressive biological behaviour in the paediatric population. Complete
      surgical excision, where possible, is the ideal. This case report discusses the
      multidisciplinary, surgical management of two complex cases of large juvenile
      ossifying fibroma (JOF), involving the orbit. Both patients underwent resection
      of the orbital ossifying fibroma with no macroscopic evidence of recurrence at 4
      years follow-up. Full functional outcome was achieved with preservation of vision
      and facial nerve function as well as good facial symmetry and aesthetics. The
      successful surgical outcome of these cases was due to a combination of a
      multidisciplinary team approach, rigorous pre-operative planning, maximal tumour
      resection, and the use of a novel surgical technique involving a medial zygomatic
      orbito-maxillary rotational osteotomy.

PMID- 21741887
TI  - The repair function of the multifunctional DNA repair/redox protein APE1 is
      neuroprotective after ionizing radiation.
AB  - Although exposure to ionizing radiation (IR) can produce significant
      neurotoxicity, the mechanisms mediating this toxicity remain to be determined.
      Previous studies using neurons isolated from the central nervous system show that
      IR produces reactive oxygen species and oxidative DNA damage in those cells.
      Because the base excision DNA repair pathway repairs single-base modifications
      caused by ROS, we asked whether manipulating this pathway by altering APE1
      expression would affect radiation-induced neurotoxicity. In cultures of adult
      hippocampal and sensory neurons, IR produces DNA damage as measured by
      phosphorylation of histone H2A.X and results in dose-dependent cell death. In
      isolated sensory neurons, we demonstrate for the first time that radiation
      decreases the capsaicin-evoked release of the neuropeptide CGRP. Reducing APE1
      expression in cultured cells augments IR-induced neurotoxicity, whereas
      overexpressing APE1 is neuroprotective. Using lentiviral constructs with a
      neuronal specific promoter that selectively expresses APE1s different functions
      in neurons, we show that selective expression of the DNA repair competent (redox
      inactive) APE1 constructs in sensory neurons resurrects cell survival and
      neuronal function, whereas use of DNA-repair deficient (redox active) constructs
      is not protective. Use of an APE1 redox-specific inhibitor, APX3330, also
      facilitates neuronal protection against IR-induced toxicity. These results
      demonstrate for the first time that the repair function of APE1 is required to
      protect both hippocampal and DRG neuronal cultures--specifically neuronal cells-
      from IR-induced damage, while the redox activity of APE1 does not appear to be
      involved.

PMID- 21741890
TI  - Medicoeconomic evaluation of total disc replacement based on French National
      Health Care System data.
AB  - INTRODUCTION: Total disc replacement (TDR) has existed since 1984 but is not
      covered by the French national healthcare system (Securite Sociale). The present
      study assessed clinical outcomes, and also pre-, peri- and postoperative
      treatment costs. HYPOTHESIS: Surgical management of low back pain (LBP) provides
      medical and economic benefit. MATERIALS AND METHODS: A prospective study
      recruited 19 patients in the Nice University Hospital Center (France); mean age,
      41 years; 15 female. Inclusion criteria were: age less than 60 years; chronic low
      back pain (LBP) with single-segment discopathy; work related injuries and
      patients not covered under the General provision of the Securite Sociale were
      excluded. VAS, Oswestry and SF36 scores and return to work capability were
      analyzed. The local national health insurance branch office (Caisse Primaire
      d'Assurance Maladie [CPAM]) provided detailed coverage data for a 39-month period
      around the operation. RESULTS: Revision surgery was required for one instance of
      vertebral fracture. Preoperative follow-up was 14 months, postoperative FU 21
      months and the perioperative period 4 months. LBP and quality of life showed
      improvement. Seventy-nine percent of patients reported satisfaction, 59% returned
      to work, and 84% had leisure activity. Total CPAM payout (reimbursement) was
      ?399,082. Daily sickness benefit and disability compensation were the main cost
      items. Mean TDR cost per patient was ?6833. Mean reimbursements were 19% lower
      post- than preoperatively. Pre- and postoperative clinical results did not
      correlate, while pre- and postoperative reimbursement costs did, as did cost and
      postoperative clinical status (r=-0.72). Preoperative cost was a predictive
      factor for postoperative clinical result. DISCUSSION: TDR achieves favorable
      medicoeconomic results. LEVEL OF EVIDENCE: III: case-control study.

PMID- 21741891
TI  - Ultrasound measurement of transversus abdominis during loaded, functional tasks
      in asymptomatic individuals: rater reliability.
AB  - OBJECTIVE: To examine the ability of 2 clinicians to consistently measure
      recorded contractions of the transversus abdominis (TrA) muscle via ultrasound
      imaging (USI) during lifting and reaching tasks typical of everyday or work
      related activities. DESIGN: Methodologic survey that measured inter- and
      intrarater reliability. SETTING: University laboratory. PARTICIPANTS: A subset of
      54 cine-loop images that were randomly selected from 6 randomly selected
      asymptomatic adults from a larger study that consisted of a sample of convenience
      of 20 asymptomatic adults, with a mean (SD) age of 18.8 +/- 2.5 years and mean
      (SD) body mass index of 25.5 +/- 3.5 kg/m(2). MAIN OUTCOME MEASURES: Thickness
      changes in the TrA muscle at rest and during contraction while performing 5
      functional, loaded tasks. Intraclass correlation coefficients (ICC) were used to
      estimate reliability. ICC model 2,1 was used for all reliability analyses on 3
      TrA muscle measures: minimum thickness, maximum thickness, and percentage change
      in muscle thickness. Percentage thickness change of TrA muscle was calculated as
      ([thickness(max) - thickness(min)]/thickness(min)) * 100. RESULTS: Two clinicians
      both scored 9 trials of 6 randomly selected participants (54 cine loops). Rater 1
      scored these images again 28 days later. All image information (participant,
      trial, task, and testing session) was masked. Interrater ICC (2,1) for TrA muscle
      measures were moderate (0.71 rested state, 0.83 contracted state, 0.81 percentage
      change of muscle thickness); and high for intrarater ICC (2,1) (0.97 rested
      state, 0.99 contracted state, and 0.95% change in muscle thickness). CONCLUSION:
      This study provides data for ensuring acceptable reliability of USI measures of
      TrA muscle thickness and thickness changes taken during loaded and functional
      activities. This study is the first to examine interrater and intrarater
      reliability of recorded cine loop images of asymptomatic adults in upright
      positions on 3 measures of TrA muscle activation (minimum, maximum, and percent
      change in muscle thickness). Reliable USI measures of TrA muscle thickness
      changes meet the ongoing need for clinicians' knowledge of proper and
      sufficiently adequate muscle activation in the clinical setting to assist
      progression of lumbar stabilization exercises.

PMID- 21741901
TI  - Robotic flexible ureteroscopy.

PMID- 21741913
TI  - Factors of PTSD: differential specificity and external correlates.
AB  - Posttraumatic Stress Disorder (PTSD) has been found to be a multidimensional
      disorder most likely consisting of four distinct symptom dimensions. Many studies
      have investigated the fit of two competing structural models of PTSD (King et
      al., 1998; Simms et al., 2002). However, little research has been done on the
      utility and differential external correlates of these dimensions. Meta-analysis
      was used to find the correlations between dimensions of PTSD and five external
      variables (depression, anxiety, panic, substance use, and trauma history), and
      multivariate analysis was used to find the unique contributions of each dimension
      in predicting each variable. It was found that the Simms et al. (2002) model
      better divides PTSD symptoms into specific and general factors. The relative
      specificity of each factor is discussed.

PMID- 21741914
TI  - Intrinsic dissipation in atomic force microscopy cantilevers.
AB  - In this paper we build a practical modification to the standard Euler-Bernoulli
      equation for flexural modes of cantilever vibrations most relevant for operation
      of AFM in high vacuum conditions. This is done by the study of a new internal
      dissipation term into the Euler-Bernoulli equation. This term remains valid in
      ultra-high vacuum, and becomes particularly relevant when viscous dissipation
      with the fluid environment becomes negligible. We derive a compact explicit
      equation for the quality factor versus pressure for all the flexural modes. This
      expression is used to compare with corresponding extant high vacuum experiments.
      We demonstrate that a single internal dissipation parameter and a single
      viscosity parameter provide enough information to reproduce the first three
      experimental flexural resonances at all pressures. The new term introduced here
      has a mesoscopic origin in the relative motion between adjacent layers in the
      cantilever.

PMID- 21741915
TI  - A distributed multi-GPU system for high speed electron microscopic tomographic
      reconstruction.
AB  - Full resolution electron microscopic tomographic (EMT) reconstruction of large
      scale tilt series requires significant computing power. The desire to perform
      multiple cycles of iterative reconstruction and realignment dramatically
      increases the pressing need to improve reconstruction performance. This has
      motivated us to develop a distributed multi-GPU (graphics processing unit) system
      to provide the required computing power for rapid constrained, iterative
      reconstructions of very large three-dimensional (3D) volumes. The participating
      GPUs reconstruct segments of the volume in parallel, and subsequently, the
      segments are assembled to form the complete 3D volume. Owing to its power and
      versatility, the CUDA (NVIDIA, USA) platform was selected for GPU implementation
      of the EMT reconstruction. For a system containing 10 GPUs provided by 5 GTX295
      cards, 10 cycles of SIRT reconstruction for a tomogram of 4096(2) * 512 voxels
      from an input tilt series containing 122 projection images of 4096(2) pixels
      (single precision float) takes a total of 1845 s of which 1032 s are for
      computation with the remainder being the system overhead. The same system takes
      only 39 s total to reconstruct 1024(2) * 256 voxels from 122 1024(2) pixel
      projections. While the system overhead is non-trivial, performance analysis
      indicates that adding extra GPUs to the system would lead to steadily enhanced
      overall performance. Therefore, this system can be easily expanded to generate
      superior computing power for very large tomographic reconstructions and
      especially to empower iterative cycles of reconstruction and realignment.

PMID- 21741916
TI  - Using carbon nanotube probes for high-resolution three-dimensional imaging of
      cells.
AB  - While atomic force microscopy (AFM) has become a promising tool for visualizing
      membrane morphology of cells, many studies have reported the presence of
      artifacts such as cliffs on the edges of cells. These artifacts shield important
      structural features such as lamellopodia, filopodia, microvilli and membrane
      ridges, which represent characteristic status in signaling processes such as
      spreading and activation. These cliff-like edges arise from a premature contact
      of the probe side contact with the cell prior to the probe top apex-cell contact.
      Carbon nanotube (CNT) modified AFM probes were utilized to address this drawback.
      Using rat basophilic leukemia (RBL) cells, this work revealed that CNT probes
      diminish cliff-like artifacts and enabled visualization of entire membrane
      morphology and structural features in three dimensions. The high aspect ratio of
      CNT probes provides a very effective remedy to the cliff-like artifacts as well
      as tip convolution of conventional probes, which shall enhance the validity and
      application of AFM in cellular biology research.

PMID- 21741917
TI  - Breakdown of the dipole approximation in core losses.
AB  - The validity of the dipole approximations commonly used in the inelastic
      scattering theory for transmission electron microscopy is reviewed. Both
      experimental and numerical arguments are presented, emphasizing that the dipole
      approximations cause significant errors of the order of up to 25% even at small
      momentum transfer. This behavior is attributed mainly to non-linear contributions
      to the dynamic form factor due to the overlap of wave functions.

PMID- 21741918
TI  - High-angle triple-axis specimen holder for three-dimensional diffraction contrast
      imaging in transmission electron microscopy.
AB  - Electron tomography requires a wide angular range of specimen-tilt for a reliable
      three-dimensional (3D) reconstruction. Although specimen holders are commercially
      available for tomography, they have several limitations, including tilting
      capability in only one or two axes at most, e.g. tilt-rotate. For amorphous
      specimens, the image contrast depends on mass and thickness only and the single
      tilt holder is adequate for most tomographic image acquisitions. On the other
      hand, for crystalline materials where image contrast is strongly dependent on
      diffraction conditions, current commercially available tomography holders are
      inadequate, because they lack tilt capability in all three orthogonal axes needed
      to maintain a constant diffraction condition over the whole tilt range. We have
      developed a high-angle triple-axis (HATA) tomography specimen holder capable of
      high-angle tilting for the primary horizontal axis with tilting capability in the
      other (orthogonal) horizontal and vertical axes. This allows the user to trim the
      specimen tilt to obtain the desired diffraction condition over the whole tilt
      range of the tomography series. To demonstrate its capabilities, we have used
      this triple-axis tomography holder with a dual-axis tilt series (the specimen was
      rotated by 90 degrees  ex-situ between series) to obtain tomographic
      reconstructions of dislocation arrangements in plastically deformed austenitic
      steel foils.

PMID- 21741919
TI  - DARPP-32 increases interactions between epidermal growth factor receptor and
      ERBB3 to promote tumor resistance to gefitinib.
AB  - BACKGROUND & AIMS: Dopamine and adenosine 3',5'-cyclic monophosphate-regulated
      phosphoprotein, Mr 32000 (DARPP-32), is overexpressed during gastric
      carcinogenesis. Gastric tumors can become resistant to gefitinib, an inhibitor of
      the epidermal growth factor receptor (EGFR). We investigated the role of DARPP-32
      in gastric tumor resistance to gefitinib. METHODS: Cell survival was determined
      by clonogenic survival and ATP-Glo Viability Assays. Apoptosis was assessed by
      Annexin-V and immunoblot analyses. The association between DARPP-32 and EGFR was
      evaluated by immunofluorescence and co-immunoprecipitation assays. Findings were
      validated in mice with gastric xenograft tumors. DARPP-32 expression was reduced
      using small hairpin RNAs in the human gastric cancer cell lines SNU-16 and MKN-45
      cells. RESULTS: Overexpression of DARPP-32 in MKN-28 cells, which do not normally
      express DARPP-32, blocked gefitinib-induced apoptosis and increased the drug's
      IC(50) 10-fold, compared to that of control cells (P < .01). Reduced expression
      of DARPP-32 in SNU-16 cells increased the sensitivity to gefitinib (P < .01).
      DARPP-32 activated phosphatidylinositol-3-kinase-AKT signaling, increased
      stability of the EGFR, and suppressed EGF- or gefitinib-induced degradation of
      the EGFR. DARPP-32 colocalized with EGFR on the cell membrane in a complex with
      EGFR and the EGF receptor ERBB3. DARPP-32-mediated resistance to gefitinib
      resulted from increased phosphorylation of and interaction between EGFR and
      ERBB3, which led to phosphorylation of AKT (at serine 473). Knockdown of DARPP-32
      in gastric cancer cells reduced the mean size of tumors in mice and increased
      their response to gefitinib. CONCLUSIONS: DARPP-32 promotes resistance of gastric
      cancer cells to gefitinib by promoting interaction between EGFR and ERBB3 and
      activating phosphatidylinositol-3-kinase-AKT signaling.

PMID- 21741920
TI  - Early changes in natural killer cell function indicate virologic response to
      interferon therapy for hepatitis C.
AB  - BACKGROUND & AIMS: Mathematical modeling of hepatitis C virus (HCV) kinetics
      indicated that cellular immune responses contribute to interferon (IFN)-induced
      clearance of HCV. We investigated a potential role of natural killer (NK) cells
      in this process. METHODS: Phenotype and function of blood and liver NK cells were
      studied during the first 12 weeks of treatment with pegylated IFN-alfa and
      ribavirin, the time period used to define the early virological response.
      RESULTS: Within hours of treatment initiation, NK cells of patients that had an
      early virological response increased expression of activating receptors NKG2D,
      NKp30, and CD16 and decreased expression of NKG2C and 2B4, along with inhibitory
      receptors SIGLEC7 and NKG2A, resulting in NK cell activation. NK cell
      cytotoxicity, measured by degranulation and tumor necrosis factor-related
      apoptosis-inducing ligand production, peaked after 24 hours (P<.01), concomitant
      with an increase in alanine aminotransferase levels (P<.05), whereas IFN-gamma
      production decreased within 6 hours and did not recover for more than 4 weeks
      (P<.05). NK cells from liver biopsies taken 6 hours after treatment initiation
      had increased numbers of cytotoxic CD16+NK cells (P<.05) and a trend toward
      increased production of tumor necrosis factor-related apoptosis-inducing ligand.
      Degranulation of peripheral blood NK cells correlated with treatment-induced,
      first-phase decreases in viral load (P<.05) and remained higher in early
      virological responders than in nonresponders for weeks. CONCLUSIONS: IFN
      activates NK cells early after treatment is initiated. Their cytotoxic function,
      in particular, is strongly induced, which correlates to virologic response.
      Therefore, NK cell activation indicates responsiveness to IFN-alpha-based
      treatment and suggests the involvement of the innate immune cells in viral
      clearance.

PMID- 21741921
TI  - Gastrointestinal microbiome signatures of pediatric patients with irritable bowel
      syndrome.
AB  - BACKGROUND & AIMS: The intestinal microbiomes of healthy children and pediatric
      patients with irritable bowel syndrome (IBS) are not well defined. Studies in
      adults have indicated that the gastrointestinal microbiota could be involved in
      IBS. METHODS: We analyzed 71 samples from 22 children with IBS (pediatric Rome
      III criteria) and 22 healthy children, ages 7-12 years, by 16S ribosomal RNA gene
      sequencing, with an average of 54,287 reads/stool sample (average 454 read length
      = 503 bases). Data were analyzed using phylogenetic-based clustering (Unifrac),
      or an operational taxonomic unit (OTU) approach using a supervised machine
      learning tool (randomForest). Most samples were also hybridized to a microarray
      that can detect 8741 bacterial taxa (16S rRNA PhyloChip). RESULTS: Microbiomes
      associated with pediatric IBS were characterized by a significantly greater
      percentage of the class gamma-proteobacteria (0.07% vs 0.89% of total bacteria,
      respectively; P < .05); 1 prominent component of this group was Haemophilus
      parainfluenzae. Differences highlighted by 454 sequencing were confirmed by high
      resolution PhyloChip analysis. Using supervised learning techniques, we were able
      to classify different subtypes of IBS with a success rate of 98.5%, using limited
      sets of discriminant bacterial species. A novel Ruminococcus-like microbe was
      associated with IBS, indicating the potential utility of microbe discovery for
      gastrointestinal disorders. A greater frequency of pain correlated with an
      increased abundance of several bacterial taxa from the genus Alistipes.
      CONCLUSIONS: Using 16S metagenomics by PhyloChip DNA hybridization and deep 454
      pyrosequencing, we associated specific microbiome signatures with pediatric IBS.
      These findings indicate the important association between gastrointestinal
      microbes and IBS in children; these approaches might be used in diagnosis of
      functional bowel disorders in pediatric patients.

PMID- 21741922
TI  - A conservative and minimally invasive approach to necrotizing pancreatitis
      improves outcome.
AB  - BACKGROUND & AIMS: Treatment of patients with necrotizing pancreatitis has become
      more conservative and less invasive, but there are few data from prospective
      studies to support the efficacy of this change. We performed a prospective
      multicenter study of treatment outcomes among patients with necrotizing
      pancreatitis. METHODS: We collected data from 639 consecutive patients with
      necrotizing pancreatitis, from 2004 to 2008, treated at 21 Dutch hospitals. Data
      were analyzed for disease severity, interventions (radiologic, endoscopic,
      surgical), and outcome. RESULTS: Overall mortality was 15% (n=93). Organ failure
      occurred in 240 patients (38%), with 35% mortality. Treatment was conservative in
      397 patients (62%), with 7% mortality. An intervention was performed in 242
      patients (38%), with 27% mortality; this included early emergency laparotomy in
      32 patients (5%), with 78% mortality. Patients with longer times between
      admission and intervention had lower mortality: 0 to 14 days, 56%; 14 to 29 days,
      26%; and >29 days, 15% (P<.001). A total of 208 patients (33%) received
      interventions for infected necrosis, with 19% mortality. Catheter drainage was
      most often performed as the first intervention (63% of cases), without additional
      necrosectomy in 35% of patients. Primary catheter drainage had fewer
      complications than primary necrosectomy (42% vs 64%, P=.003). Patients with
      pancreatic parenchymal necrosis (n=324), compared with patients with only
      peripancreatic necrosis (n=315), had a higher risk of organ failure (50% vs 24%,
      P<.001) and mortality (20% vs 9%, P<.001). CONCLUSIONS: Approximately 62% of
      patients with necrotizing pancreatitis can be treated without an intervention and
      with low mortality. In patients with infected necrosis, delayed intervention and
      catheter drainage as first treatment improves outcome.

PMID- 21741923
TI  - Disruption of the mouse protein tyrosine kinase 6 gene prevents STAT3 activation
      and confers resistance to azoxymethane.
AB  - BACKGROUND & AIMS: Protein tyrosine kinase 6 (PTK6) is expressed throughout the
      gastrointestinal tract and is a negative regulator of proliferation that promotes
      differentiation and DNA-damage-induced apoptosis in the small intestine. PTK6 is
      not expressed in normal mammary gland, but is induced in most human breast
      tumors. Signal transducer and activator of transcription 3 (STAT3) mediates
      pathogenesis of colon cancer and is a substrate of PTK6. We investigated the role
      of PTK6 in colon tumorigenesis. METHODS: Ptk6+/+ and Ptk6-/- mice were injected
      with azoxymethane alone or in combination with dextran sodium sulfate; formation
      of aberrant crypt foci and colon tumors was examined. Effects of disruption of
      Ptk6 on proliferation, apoptosis, and STAT3 activation were examined by
      immunoblot and immunohistochemical analyses. Regulation of STAT3 activation was
      examined in the HCT116 colon cancer cell line and young adult mouse colon cells.
      RESULTS: Ptk6-/- mice developed fewer azoxymethane-induced aberrant crypt foci
      and tumors. Induction of PTK6 increased apoptosis, proliferation, and STAT3
      activation in Ptk6+/+ mice injected with azoxymethane. Disruption of Ptk6
      impaired STAT3 activation following azoxymethane injection, and reduced active
      STAT3 levels in Ptk6-/- tumors. Stable knockdown of PTK6 reduced basal levels of
      active STAT3, as well as activation of STAT3 by epidermal growth factor in HCT116
      cells. Disruption of Ptk6 reduced activity of STAT3 in young adult mouse colon
      cells. CONCLUSIONS: PTK6 promotes STAT3 activation in the colon following
      injection of the carcinogen azoxymethane and regulates STAT3 activity in mouse
      colon tumors and in the HCT116 and young adult mouse colon cell lines. Disruption
      of Ptk6 decreases azoxymethane-induced colon tumorigenesis in mice.

PMID- 21741924
TI  - Lipotoxicity in NASH.

PMID- 21741925
TI  - Mutation in the mitochondrial translation elongation factor EFTs results in
      severe infantile liver failure.
AB  - BACKGROUND & AIMS: Multiple respiratory chain deficiencies represent a common
      cause of mitochondrial diseases and often result in hepatic failure. A
      significant fraction of patients present mitochondrial DNA depletion but a number
      of cases remain unexplained. The aim of our study was to identify the disease
      causing gene in a kindred with intrauterine growth retardation, neonatal lactic
      acidosis, liver dysfunction and multiple respiratory chain deficiency in muscle.
      METHODS: Homozygosity mapping was performed by 50K SNP genotyping and candidate
      genes were successively analyzed by direct sequencing on genomic DNA of the
      family members. RESULTS: SNP genotyping detected several regions of homozygosity
      in which we focused our attention to genes involved in mitochondrial translation.
      We sequenced the TSFM gene, encoding the mitochondrial translation factor EFTs
      and identified a homozygous mutation changing a highly conserved arginine into a
      tryptophan (R312W). CONCLUSIONS: This mutation has been previously reported in
      two unrelated kindred presenting two distinct syndromes (fatal mitochondrial
      encephalomyopathy and hypertrophic cardiomyopathy respectively). The description
      of a third syndrome associated with a same TSFM mutation gives support to the
      broad clinical and genetic heterogeneity of mitochondrial translation
      deficiencies in human. It suggests that mitochondrial translation deficiency
      represents a growing cause of hepatic failure of mitochondrial origin in infants.

PMID- 21741926
TI  - The use of sirolimus should be restricted in liver transplantation.
AB  - Sirolimus and mTOR inhibitors are important additions to the therapeutic
      armamentarium to prevent allograft rejection, but their role in liver
      transplantation is evolving. De novo use of Sirolimus in the early post
      transplant period has undoubtedly been influenced by the high incidence of
      hepatic artery thrombosis and decreased patient and graft survival leading to a
      black box warning. The jury remains undecided on the role of conversion from CNIs
      to mTOR inhibitors in those developing renal insufficiency and it must be noted
      that a second warning was issued by the FDA because of decreased survival in
      those conversion studies. Finally, the anti-atherogenic, antiviral, and anti
      neoplastic effects associated with Sirolimus, which might favor their use in
      certain liver transplant patients, need further evaluation before firm
      recommendations can be made.

PMID- 21741927
TI  - Muddy waters: Hypothermia does not work?

PMID- 21741928
TI  - WITHDRAWN: Adrenaline - Proven benefit in cardiac arrest at last?
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi:10.1016/j.resuscitation.2011.07.001.
      The duplicate article has therefore been withdrawn.

PMID- 21741929
TI  - Plasmodium falciparum and helminth coinfections among schoolchildren in relation
      to agro-ecosystems in Mvomero District, Tanzania.
AB  - BACKGROUND: In Sub-Saharan Africa, some individuals infected with malaria are
      also infected with helminths. However, the magnitude and distribution of such
      coinfections in relation to eco-systems remains poorly defined. This study was
      undertaken to determine the prevalence of Plasmodium falciparum and helminth
      coinfections among schoolchildren in relation to agro-ecosystems in Mvomero
      District, Tanzania. METHODS: The agro-ecosystems were categorised as sugarcane,
      traditional flooding rice irrigation, improved non-flooding rice irrigation and
      savannah. Schoolchildren had their blood examined for P. falciparum and
      Wuchereria bancrofti; urine for Schistosoma haematobium and stool for intestinal
      helminths. Blood samples were also examined for haemoglobin concentration.
      RESULTS: A total of 578 schoolchildren (mean age = 7.96 years) were involved in
      the study. Overall, 60% of all schoolchildren had at least an infection of either
      P. falciparum, W. bancrofti, S. haematobium or hookworm. The highest prevalence
      of P. falciparum (75.3%), W. bancrofti (62.9%) and hookworm (24.7%) infections
      was observed among children in flooding rice irrigation ecosystem. P.
      falciparum+S. haematobium (10.9%) and P. falciparum+W. bancrofti (11.1%) were the
      most prevalent types of coinfection in the area. The highest prevalence of double
      parasitic infections was observed among children in the flooding rice irrigation
      ecosystems. The risk for acquiring coinfections of P. falciparum+W. bancrofti was
      significantly higher among children in the flooding rice irrigation ecosystem.
      Forty-five (7.8%) children were coinfected with three types of parasitic
      infections. The risk of acquiring triple infection among children from flooding
      rice irrigation was higher for P. falciparum+S. haematobium+W. bancrofti
      (p<0.001). Seven schoolchildren (1.2%) were found infected with four parasites
      and all were from the flooding rice irrigation ecosystem. Significantly high P.
      falciparum geometric parasite density was observed among children coinfected with
      either hookworms or W. bancrofti (p<0.001). On average, 17.8% (103/578) of the
      children had enlarged spleens. Over 3- and 4-folds increase in the risk of having
      an enlarged spleen were observed among children coinfected with P. falciparum+S.
      haematobium and P. falciparum+W. bancrofti, respectively. The overall prevalence
      of anaemia (<11.5g/dl) was 61.9% (358/578). CONCLUSION: Malaria-helminth
      coinfections are prevalent among schoolchildren in rural Tanzania and the pattern
      varies between agro-ecosystems. Results of this study suggest that integrated
      control of malaria and helminthes should be designed based on the local agro
      ecosystems.

PMID- 21741930
TI  - B4GALNT3 expression predicts a favorable prognosis and suppresses cell migration
      and invasion via beta1 integrin signaling in neuroblastoma.
AB  - beta1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) promotes the formation
      of GalNAcbeta1,4GlcNAc (LacdiNAc or LDN). Drosophila beta1,4-N
      acetylgalactosaminyltransferase A (B4GALNTA) contributes to the synthesis of LDN,
      which helps regulate neuronal development. In this study, we investigated the
      expression and role of B4GALNT3 in human neuroblastoma (NB). We used IHC analysis
      to examine 87 NB tumors, and we identified correlations between B4GALNT3
      expression and clinicopathologic factors, including patient survival. Effects of
      recombinant B4GALNT3 on cell behavior and signaling were studied in SK-N-SH and
      SH-SY5Y NB cells. Increased expression of B4GALNT3 in NB tumors correlated with a
      favorable histologic profile (P < 0.001, chi2 test) and early clinical staging (P
      = 0.041, chi2 test) and was a favorable prognostic factor for survival as
      evaluated by univariate and multivariate analyses. Reexpression of B4GALNT3 in SK
      N-SH and SH-SY5Y cells suppressed cell proliferation, colony formation,
      migration, and invasion. Moreover, B4GALNT3 increased the LacdiNAc modification
      of beta1 integrin, leading to decreased phosphorylation of focal adhesion kinase
      (FAK), Src, paxillin, Akt, and ERK1/2. B4GALNT3-mediated suppression of cell
      migration and invasion were substantially reversed by concomitant expression of
      constitutively active Akt or MEK. We conclude that B4GALNT3 predicts a favorable
      prognosis for NB and suppresses the malignant phenotype via decreasing beta1
      integrin signaling.

PMID- 21741931
TI  - Interleukin-17A promotes early but attenuates established disease in crescentic
      glomerulonephritis in mice.
AB  - T helper (Th)17 cells might contribute to immune-mediated renal injury. Thus, we
      sought to define the time course of IL-17A-induced kidney damage and examined the
      relation between Th17 and Th1 cells in a model of crescentic anti-glomerular
      basement membrane glomerulonephritis. Renal injury and immune responses were
      assessed in wild-type and in IL-17A-deficient mice on days 6, 14, and 21 of
      disease development. On day 6, when mild glomerulonephritis developed, IL-17A
      deficient mice were protected from renal injury. On day 14, when more severe
      disease developed, protection from renal injury due to IL-17A deficiency was less
      evident. On day 21, when crescentic glomerulonephritis was fully established,
      disease was enhanced in IL-17A(-/-) mice, with increased glomerular T-cell
      accumulation and fibrin deposition, and augmented Th1 responses. Mice lacking the
      Th17-promoting cytokine, IL-23 (p19), also developed more severe disease than
      wild-type animals on day 21. In contrast, mice deficient in the key Th1-promoting
      cytokine, IL-12 (p35), had decreased Th1 and increased Th17 responses and
      developed less severe crescentic glomerulonephritis than wild-type animals. These
      studies show that IL-17A contributes to early glomerular injury, but it
      attenuates established crescentic glomerulonephritis by suppressing Th1
      responses. They provide further evidence that Th1 cells mediate crescentic injury
      in this model and that Th1 and Th17 cells counterregulate each other during
      disease development.

PMID- 21741932
TI  - The tripeptide KdPT protects from intestinal inflammation and maintains
      intestinal barrier function.
AB  - Treatment options for inflammatory bowel disease (IBD) are incompletely helpful,
      and surgery is often needed. One promising class of future therapeutic agents for
      IBD is melanocortin-related peptides, which exhibit potent immunomodulatory
      effects. We investigated KdPT, a tripeptide derivative of the C-terminus of alpha
      melanocyte-stimulating hormone, as an anti-inflammatory small molecule in vivo
      and in vitro. Intestinal inflammation was studied after oral administration of
      dextran sodium sulfate and in IL-10 gene-deficient mice. The effects of KdPT on
      key colonic epithelial cell functions were studied in vitro and in vivo by
      evaluating proliferation, wound healing, transepithelial resistance, and
      expression of tight junction proteins. Melanin assays were performed to determine
      the melanotropic effects of KdPT. KdPT-treated animals showed markedly reduced
      severity of inflammation in both colitis models. In colonic epithelial cells,
      KdPT increased proliferation, accelerated closure of wounds, and improved
      transepithelial electrical resistance after stimulation with interferon
      gamma/tumor necrosis factor-alpha. Moreover, treatment with KdPT also prevented
      the loss of tight junction protein expression and improved barrier function in
      vivo. KdPT acted independently of IL-1 receptor type I in vivo and did not affect
      melanogenesis in vitro. KdPT is capable of attenuating the course of experimental
      colitis in different models and maintains epithelial cell function. Furthermore,
      KdPT does not induce pigmentation, emphasizing the potential of this small
      molecule for the future treatment of IBD.

PMID- 21741933
TI  - Involvement of GLTSCR2 in the DNA Damage Response.
AB  - The cellular DNA damage response (DDR) ensures genomic stability and protects
      against genotoxic stresses. Conversely, defects in the DDR contribute to genome
      instability, with the resulting accumulated genetic changes capable of inducing
      neoplastic transformation. Thus, DDR is central to both the mechanism of
      oncogenesis and cancer therapy. Specifically, DDR is accomplished via a
      complicated meshwork of evolutionary conserved proteins, including ATM, ATR, and
      phospho-H2AX (gammaH2AX). GLTSCR2 is a nucleolar protein believed to function as
      a tumor suppressor, although its exact molecular mechanisms have yet to be fully
      elucidated. As a result of our research pertaining to the role of GLTSCR2 in
      tumor suppression, we have determined that GLTSCR2 is involved in DDR. Under
      genotoxic conditions, such as cellular exposure to UV radiation or radiomimetic
      drugs, GLTSCR2 expression increased and later mobilized to the nucleoplasm.
      Moreover, GLTSCR2 knockdown attenuated both the presence of phospho-H2AX at the
      nuclear foci and the phosphorylation of multiple DDR proteins, including ATM,
      ATR, Chk2, Chk1, and H2AX. In addition, the decreased expression of GLTSCR2
      sensitized cells to DNA damage, delayed DNA repair, and abolished G2/M checkpoint
      activation. Our observations indicate that GLTSCR2 is a key component of DDR and
      GLTSCR2 seems to act as a tumor suppressor by participating in optimal DDR
      because DNA damage is a frequent and crucial event in oncogenesis.

PMID- 21741934
TI  - Characterization of DISC formation and TNFR1 translocation to mitochondria in TNF
      alpha-treated hepatocytes.
AB  - Tumor necrosis factor receptor 1 (TNFR1) activation in hepatocytes can trigger
      apoptotic or inflammatory signaling. The factors that determine which signaling
      pathway dominates are not clear and are thought to relate to the efficiency of
      death-inducing signaling complex (DISC) formation. However, the steps involved in
      DISC formation in hepatocytes are poorly understood. In characterizing DISC
      formation within cultured hepatocytes, we demonstrated that TNF-alpha exposure
      leads to the rapid formation of a DISC involving TNF-alpha, the TNFR-associated
      death domain adaptor molecule (TRADD), the Fas-associated death domain adaptor
      molecule (FADD), caspase-8, TNFR-associated factor 2 (TRAF2), and receptor
      interacting protein (RIP). The inclusion of the sensitizing agent actinomycin D
      both accelerated and amplified the appearance of the DISC. Notably, TNFR1 along
      with some DISC components also appeared within mitochondria within 30 minutes.
      Whereas TNFR1 consistently co-localized with the TRADD, FADD, the caspase-8, and
      TRAF2 in the cytosolic fraction, TNFR1 in the mitochondria was associated only
      with caspase-8 after TNF-alpha exposure. Similar observations were made in vivo
      using TNF-alpha with D-galactosamine. Actinomycin D alone also enhanced the
      appearance of DISC components in both cytosol and the mitochondria. Thus the DISC
      that includes TNFR1 forms in the cytosol of hepatocytes under both survival and
      pro-apoptotic conditions. The observations also suggest that TNF-alpha-mediated
      signaling includes the translocation of TNFR1 to mitochondria.

PMID- 21741935
TI  - Regulator of calcineurin 1 (Rcan1) is required for the development of pulmonary
      eosinophilia in allergic inflammation in mice.
AB  - The presence of eosinophils in the lung is often regarded as a defining feature
      of asthma. On allergen stimulation, numbers of eosinophils and their progenitors
      are increased in both the bone marrow and lungs. Eosinophil progenitors provide
      an ongoing supply of mature eosinophils. Here, we report that deficiency in the
      regulator of calcineurin 1 gene (Rcan1) leads to a near-complete absence of
      eosinophilia in ovalbumin-induced allergic asthma in mice. In the absence of
      Rcan1, bone marrow cells produce significantly fewer eosinophils in vivo and in
      vitro on interleukin-5 stimulation. Importantly, eosinophil progenitor
      populations are significantly reduced in both naive and ovalbumin-challenged
      Rcan1(-/-) mice. Bone marrow cells from Rcan1(-/-) mice are capable of developing
      into fully mature eosinophils, suggesting that Rcan1 is required for eosinophil
      progenitor production but may not be necessary for eosinophil maturation. Thus,
      Rcan1 represents a novel contributor in the development of eosinophilia in
      allergic asthma through regulation of eosinophil progenitor production.

PMID- 21741936
TI  - Regulation of CRIg expression and phagocytosis in human macrophages by
      arachidonate, dexamethasone, and cytokines.
AB  - Although the importance of the macrophage complement receptor immunoglobulin
      (CRIg) in the phagocytosis of complement opsonized bacteria and in inflammation
      has been established, the regulation of CRIg expression remains undefined.
      Because cellular activation during inflammation leads to the release of
      arachidonate, a stimulator of leukocyte function, we sought to determine whether
      arachidonate regulates CRIg expression. Adding arachidonate to maturing human
      macrophages and to prematured CRIg(+) macrophages caused a significant decrease
      in the expression of cell-surface CRIg and CRIg mRNA. This effect was independent
      of the metabolism of arachidonate via the cyclooxygenase and lipoxygenase
      pathways, because it was not inhibited by the nonsteroidal anti-inflammatory
      drugs indomethacin and nordihydroguaiaretic acid. Studies with specific
      pharmacological inhibitors of arachidonate-mediated signaling pathways showed
      that protein kinase C was involved. Administration of dexamethasone to
      macrophages caused an increase in CRIg expression. Studies with proinflammatory
      and immunosuppressive cytokines showed that IL-10 increased, but interferon
      gamma, IL-4, and transforming growth factor-beta1 decreased CRIg expression on
      macrophages. This down- and up-regulation of CRIg expression was reflected in a
      decrease and increase, respectively, in the phagocytosis of complement opsonized
      Candida albicans. These data suggest that a unique inflammatory mediator network
      regulates CRIg expression and point to a mechanism by which arachidonate and
      dexamethasone have reciprocal effects on inflammation.

PMID- 21741937
TI  - Up-regulation of the chemokine CCL18 by macrophages is a potential
      immunomodulatory pathway in cutaneous T-cell lymphoma.
AB  - Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma
      (CTCL), which can deteriorate from patch stage to dermal-based tumors and
      systemic involvement in years. The interaction of chemokines in the skin with
      CTCL cells might have implications for the pathogenesis of the disease. In this
      study, we show by PCR analysis and immunofluorescence staining that the chemokine
      CCL18 is present in skin biopsy specimens of patients with MF and its precursor
      form parapsoriasis en plaque but not in healthy tissue. In addition, the serum
      levels of CCL18 were increased threefold in MF patients compared with those in
      healthy controls. In skin, CCL18 was specifically expressed by CD163(+) CD209(+)
      macrophages at the invasive margin of the tumor and not expressed by mature
      CD208(+) dendritic cells in the center of the tumor. The chemokine CCL17 was, by
      contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but
      not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells
      and abolished the CXCL12-induced growth of a CTCL cell line. These data link the
      increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of
      the chemokine in the pathogenesis of CTCL.

PMID- 21741938
TI  - Mesenchymal stem cells stably transduced with a dominant-negative inhibitor of
      CCL2 greatly attenuate bleomycin-induced lung damage.
AB  - Acute respiratory distress syndrome (ARDS) is a crippling disease with no
      effective therapy characterized by progressive dyspnea. Mesenchymal stem cells
      (MSCs) have emerged as a new therapeutic modality for ARDS because MSCs can
      attenuate inflammation and repair the damaged tissue by differentiating into
      several cell types. Macrophages participate in the development of ARDS; however,
      MSCs only weakly modulate macrophage function. The chemokine CCL2 is a potent
      inducer of macrophage recruitment and activation, and its expression is elevated
      in patients with ARDS. We established MSCs that are stably transduced by a
      lentiviral vector expressing 7ND, a dominant-negative inhibitor of CCL2, to
      enhance the therapeutic function of MSCs. 7ND-MSCs retained the innate properties
      of MSCs and produced a large amount of 7ND. Many 7ND-MSCs were detected in
      bleomycin-treated lungs (immunostaining 24 hours after injection), suggesting
      that MSCs could work as a drug delivery tool. Mice treated with 7ND-MSCs showed
      significantly milder weight loss, lung injury, collagen content, accumulation of
      inflammatory cells and inflammatory mediators that were induced by bleomycin, and
      subsequent survival benefit. No evidence of 7ND-MSC-induced toxicity was observed
      during or after treatment. Thus, inhibiting the effects of macrophages may
      greatly enhance the ability of MSCs to effect lung repair in ARDS.

PMID- 21741939
TI  - Stage-specific remodeling of atherosclerotic lesions upon cholesterol lowering in
      LDL receptor knockout mice.
AB  - Reducing the concentration of circulating lipids leads to decreased
      cardiovascular morbidity and mortality, but the dynamic remodeling that
      established atherosclerotic lesions undergo upon lipid lowering is poorly
      understood. Early or advanced lesions in the aortic root were induced by feeding
      LDL receptor knockout mice a high-fat, high-cholesterol Western-type diet for 5
      or 9 weeks, respectively. In the first week after switching to a chow diet,
      plasma total cholesterol levels dropped 70%, but both early and advanced lesions
      increased in size. Early lesions grew because of an increase in smooth muscle
      cells; advanced lesions had an enlargement of absolute macrophage area. From 1 to
      3 weeks after the diet switch, plasma total cholesterol levels were completely
      normalized, but the size of early lesions remained stable; however, advanced
      lesions became smaller due to a reduction of the absolute macrophage area. From 3
      to 6 weeks, both early and advanced lesions progressed further, as a result of
      expansion of the absolute collagen and necrotic core area. In contrast, early
      lesions became proinflammatory, as evidenced by the increased infiltration of
      neutrophils and increased oxidative stress, probably caused by the activation of
      mast cells in the adventitia. Thus, the severity of atherosclerotic lesions
      affects their dynamic response to lipid lowering, indicating the importance of
      establishing stage-specific therapeutic protocols for the treatment of
      atherosclerosis.

PMID- 21741940
TI  - Claudin-4 levels are associated with intact alveolar fluid clearance in human
      lungs.
AB  - The removal of edema from the air spaces is a critical function of the alveolar
      barrier requiring intact tight junctions. Alveolar fluid clearance contributes to
      graft function after transplantation and is associated with survival in patients
      with acute lung injury. Claudin-4 concentrations are known to increase during
      lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice.
      This study was therefore undertaken to evaluate whether differences in lung
      expression of the tight junction protein claudin-4 are associated with alveolar
      fluid clearance or clinical measures of lung function. Alveolar fluid clearance
      rates were measured in ex vivo perfused human lungs not used for transplantation
      and were compared with histological lung injury and clinical measures of lung
      injury in the donors. Claudin-4 staining demonstrated a positive correlation with
      alveolar fluid clearance (Spearman rank correlation [r(s)] = 0.71; P < 0.003);
      however, claudin-4 staining was not strongly associated with histological
      measures of lung injury. The expression of other tight junction proteins
      (including ZO-1) was not associated with alveolar fluid clearance or claudin-4
      levels. Claudin-4 staining was lower in lungs from donors with greater impairment
      in respiratory physiology. These data suggest that claudin-4 may promote alveolar
      fluid clearance and demonstrate that the amount of claudin-4 expressed may
      provide specific information regarding alveolar epithelial barrier function that
      strengthens the link between histological changes and physiological impairment.

PMID- 21741941
TI  - In the eye of experimental cerebral malaria.
AB  - Cerebral malaria is the most severe complication of Plasmodium falciparum
      infection, accounting for 1 million deaths per year. We characterized the murine
      disease using in vivo magnetic resonance imaging (MRI) at 4.7 T, proving that
      ischemic edema is responsible for fatality. The aim of the present study was to
      identify early markers of experimental cerebral malaria using very high field
      conventional MRI (11.75 T). CBA/J mice infected with Plasmodium berghei ANKA were
      observed at an early stage of the disease, before the onset of detectable brain
      swelling and at the most acute stage of cerebral malaria. Herein, we report the
      first detection of damage to the optic and trigeminal nerves on T(2)-weighted
      MRI. The trigeminal nerves appeared hypointense, with significantly reduced
      diameter and cross-sectional area. The optic nerves were hypointense and often
      not visible. In addition, the internerve distance between the optic nerves was
      significantly and progressively reduced between the early and severest stages.
      Cranial nerve injury was the earliest anatomic hallmark of the disease, visible
      before brain edema became detectable. Thus, cranial nerve damage may manifest in
      neurologic signs, which may assist in the early recognition of cerebral malaria.

PMID- 21741942
TI  - Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately
      the levels of tumor angiogenesis and efficiency of malignant cell intravasation.
AB  - Tumor-associated neutrophils contribute to neovascularization by supplying matrix
      metalloproteinase-9 (MMP-9), a protease that has been genetically and
      biochemically linked to induction of angiogenesis. Specific roles of inflammatory
      neutrophils and their distinct proMMP-9 in the coordinate regulation of tumor
      angiogenesis and tumor cell dissemination, however, have not been addressed. We
      demonstrate that the primary tumors formed by highly disseminating variants of
      human fibrosarcoma and prostate carcinoma recruit elevated levels of infiltrating
      MMP-9-positive neutrophils and concomitantly exhibit enhanced levels of
      angiogenesis and intravasation. Specific inhibition of neutrophil influx by
      interleukin 8 (IL-8) neutralization resulted in the coordinated diminishment of
      tumor angiogenesis and intravasation, both of which were rescued by purified
      neutrophil proMMP-9. However, if neutrophil proMMP-9, naturally devoid of tissue
      inhibitor of metalloproteinases (TIMP), was delivered in complex with TIMP-1 or
      in a mixture with TIMP-2, the protease failed to rescue the inhibitory effects of
      anti-IL8 therapy, indicating that the TIMP-free status of proMMP-9 is critical
      for facilitating tumor angiogenesis and intravasation. Our findings directly link
      tumor-associated neutrophils and their TIMP-free proMMP-9 with the ability of
      aggressive tumor cells to induce the formation of new blood vessels that serve as
      conduits for tumor cell dissemination. Thus, treatment of cancers associated with
      neutrophil infiltration may benefit from specific targeting of neutrophil MMP-9
      at early stages to prevent ensuing tumor angiogenesis and tumor metastasis.

PMID- 21741943
TI  - Quartz crystal microbalance as a tool for kinetic enzymatic assays by variation
      of pH.
AB  - In this work, it is shown that the quartz crystal microbalance (QCM) can be a
      powerful and simple tool for quick and precise kinetic enzymatic assays. This is
      shown by measuring immobilized acetylcholinesterase (AChE) activity with
      variations of pH as a case study.

PMID- 21741944
TI  - Real-time analysis of living animals by electrospray ionization mass
      spectrometry.
AB  - Probe electrospray ionization (PESI) is one of the most promising methods in
      biochemical analysis because it enables us to analyze biological samples very
      quickly without any special pretreatment. Moreover, due to the small size of the
      needle tip, this method has advantages such as low invasiveness to the samples,
      making it possible to analyze the biological profiles of organs or tissues in
      living animal in situ. In this study, we performed a real-time analysis of living
      mice that delineates the differences in lipid composition of hepatocytes between
      normal and steatotic mice. In steatotic mice, the number of peaks and the ion
      abundance for triacylglycerols were much higher compared with those of control
      mice. All mice used in this study tolerated the procedure well and survived for
      more than a month until sacrificed for further analysis. To test a potential for
      medical diagnosis, human tumor tissues were also measured and we obtained
      discriminative results judged as useful for diagnostics. These results pave the
      way into the application of PESI to the in vivo analysis of biological molecules.

PMID- 21741945
TI  - Novel method for quantifying radiation-induced single-strand-break yields in
      plasmid DNA highlights 10-fold discrepancy.
AB  - The widely used agarose gel electrophoresis method for assessing radiation
      induced single-strand-break (SSB) yield in plasmid DNA involves measurement of
      the fraction of relaxed-circular (C) form that migrates independently from the
      intact supercoiled (SC) form. We rationalized that this method may underestimate
      the SSB yield since the position of the relaxed-circular form is not altered when
      the number of SSB per DNA molecule is >1. To overcome this limitation, we have
      developed a novel method that directly probes and quantifies SSBs. Supercoiled
      (3)H-pUC19 plasmid samples were irradiated with gamma-rays, alkali-denatured,
      dephosphorylated, and kinated with gamma-[(32)P]ATP, and the DNA-incorporated
      (32)P activities were used to quantify the SSB yields per DNA molecule, employing
      a standard curve generated using DNA molecules containing a known number of SSBs.
      The same irradiated samples were analyzed by agarose gel and SSB yields were
      determined by conventional methods. Comparison of the data demonstrated that the
      mean SSB yield per plasmid DNA molecule of [21.2+/-0.59]*10(-2)Gy(-1) as measured
      by direct probing is ~10-fold higher than that obtained from conventional gel
      based methods. These findings imply that the SSB yields inferred from agarose
      gels need reevaluation, especially when they were utilized in the determination
      of radiation risk.

PMID- 21741946
TI  - Comprehensive proteomic analysis of mineral nanoparticles derived from human body
      fluids and analyzed by liquid chromatography-tandem mass spectrometry.
AB  - Mineralo-protein nanoparticles (NPs) formed spontaneously in the body have been
      associated with ectopic calcifications seen in atherosclerosis, chronic
      degenerative diseases, and kidney stone formation. Synthetic NPs are also known
      to become coated with proteins when they come in contact with body fluids.
      Identifying the proteins found in NPs should help unravel how NPs are formed in
      the body and how NPs in general, be they synthetic or naturally formed, interact
      within the body. Here, we developed a proteomic approach based on liquid
      chromatography (LC) and tandem mass spectrometry (MS/MS) to determine the protein
      composition of carbonate-apatite NPs derived from human body fluids (serum,
      urine, cerebrospinal fluid, ascites, pleural effusion, and synovial fluid). LC
      MS/MS provided not only an efficient and comprehensive determination of the
      protein constituents, but also a semiquantitative ranking of the identified
      proteins. Notably, the identified NP proteins mirrored the protein composition of
      the contacting body fluids, with albumin, fetuin-A, complement C3, alpha-1
      antitrypsin, prothrombin, and apolipoproteins A1 and B-100 being consistently
      associated with the particles. Since several coagulation factors, calcification
      inhibitors, complement proteins, immune regulators, protease inhibitors, and
      lipid/molecule carriers can all become NP constituents, our results suggest that
      mineralo-protein complexes may interface with distinct biochemical pathways in
      the body depending on their protein composition. We propose that LC-MS/MS be used
      to characterize proteins found in both synthetic and natural NPs.

PMID- 21741947
TI  - An assay to quantitate reducible cysteines from nanograms of GST-fusion proteins.
AB  - Cysteine residues in proteins are targets of numerous post-translational
      modifications and play important roles in protein structure and enzymatic
      function. Consequently, understanding the full biochemistry of proteins depends
      on determining the oxidation state and availability of the residues to be
      modified. We have developed a highly sensitive assay that accurately determines
      the number of unmodified cysteine residues in GST-fusion proteins. Only picomoles
      of protein are required for each reaction, which are carried out in 96-well
      glutathione-coated plates. Free unmodified cysteine residues are labeled and
      quantified using biotin and HRP-conjugated streptavidin. Our assay can be used to
      quantify reactions targeting sulfhydryl groups in proteins. We demonstrate this
      assay using full-length and truncation mutants of the SNARE proteins syntaxin1A,
      SNAP-25B, and synaptobrevin2, which have 0-4 cysteines. We are able to accurately
      determine the number of cysteine residues in each protein and follow the
      modification of these cysteines by oxidation and reaction with NEM (N
      ethylmaleimide). This assay is as simple as running an ELISA or Western blot and,
      because of its high resolution, should allow detailed analysis of the chemistry
      of cysteine residues in proteins.

PMID- 21741948
TI  - High-throughput quantification of hydroxyproline for determination of collagen.
AB  - An accurate and high-throughput assay for collagen is essential for collagen
      research and development of collagen products. Hydroxyproline is routinely
      assayed to provide a measurement for collagen quantification. The time required
      for sample preparation using acid hydrolysis and neutralization prior to assay is
      what limits the current method for determining hydroxyproline. This work
      describes the conditions of alkali hydrolysis that, when combined with the
      colorimetric assay defined by Woessner, provide a high-throughput, accurate
      method for the measurement of hydroxyproline.

PMID- 21741949
TI  - Analysis of cholesteryl esters and diacylglycerols using lithiated adducts and
      electrospray ionization-tandem mass spectrometry.
AB  - Cholesteryl ester (CE) and diacylglycerol (DAG) molecular species are important
      lipid storage and signaling molecules. Mass spectrometric analyses of these
      lipids are complicated by the presence of isobaric molecular ions shared by these
      lipid classes and by relatively poor electrospray ionization, which is a
      consequence of an inherently weak dipole moment in these lipid classes. The
      current study demonstrates that lithiated adducts of CE and DAG molecular ions
      have enhanced ionization and lipid class-specific fragmentation in tandem mass
      spectrometry (MS/MS) scan modes, thereby allowing the implementation of
      strategies capable of lipid class-specific detection. Using neutral loss (NL)
      mode for the loss of cholestane from cholesterol esters (NL 368.5) and specific
      selected reaction monitoring for DAG molecular species, the response of specific
      molecular species to that of internal standards was determined. CE and DAG
      molecular species were quantified in human coronary artery endothelial cells
      (HCAECs) incubated with both palmitic acid and oleic acid. Furthermore, NL 368.5
      spectra revealed the oxidation of the aliphatic fatty acid residues of CE
      molecular species. Taken together, these studies demonstrate a new analytical
      approach to assessing CE and DAG molecular species that exploits the utility of
      lithiated adducts in conjunction with MS/MS approaches.

PMID- 21741950
TI  - Reference genes for the relative quantification of microRNAs in renal cell
      carcinomas and their metastases.
AB  - To obtain accurate results in miRNA expression changes between different sample
      sets using real-time quantitative polymerase chain reaction (RT-qPCR) analyses,
      normalization to reference genes that are stably expressed across the sample sets
      is generally used. A literature search of miRNA expression studies in renal cell
      carcinoma (RCC) proved that non-miRNAs such as small RNAs or mRNAs have most
      frequently been used without preceding validation of their suitability. In this
      study, the most stably expressed miRNAs were ascertained from microarray-based
      data of miRNA expression in nonmalignant and malignant samples from clear cell
      RCC and from corresponding distant RCC metastases using the geNorm and NormFinder
      algorithms. Validation experiments with RT-qPCR were performed for the four best
      ranked miRNAs (miR-28, miR-103, miR-106a, miR-151) together with the small RNU6B,
      RNU44, and RNU48 mostly described in literature. miR-28, miR-103, miR-106a, and
      RNU48 were proved as the most stably expressed genes. miR-28 is recommended as
      normalizer if only a single reference gene can be used, while the combinations of
      miR-28 and miR-103 or of miR-28, miR-103, and miR-106a, respectively, are
      preferred. RNU6B most frequently used as normalizer in miRNA expression studies
      should be abandoned in order to avoid misleading results.

PMID- 21741951
TI  - Calibration of nanowatt isothermal titration calorimeters with overflow reaction
      vessels.
AB  - Obtaining accurate results with nanowatt titration calorimeters with overflow
      cells requires mass calibration of the buret injection volume, chemical
      calibration of the reaction vessel effective volume, and chemical calibration of
      the calorimetric factor used to convert the measured electrical signal to heat
      rate. Potential errors in electrical calibration of power compensation
      calorimeters require validation of the calorimetric factor with chemical
      reactions with accurately known stoichiometries and enthalpy changes. The
      effective volume of the reaction vessel can be determined from the endpoint of a
      quantitative reaction with known stoichiometries. Methods for calibration and
      potential calibration errors to be avoided are described. Publication of results
      obtained must include data on calibrations and sufficient raw data to assess
      precision and accuracy of the results.

PMID- 21741952
TI  - Development of a universal glycosyltransferase assay amenable to high-throughput
      formats.
AB  - The development of a general 1-Zn(II) nucleoside diphosphate (NDP) sensor assay
      for rapid evaluation of glycosyltransferase (GT) activity is described. The 1
      Zn(II) NDP sensor assay offers submicromolar sensitivity, compatibility with both
      purified enzymes and crude cell extracts, and exquisite selectivity for NDPs over
      the corresponding NDP-sugars. Thus, the 1-Zn(II) NDP sensor assay is anticipated
      to offer broad applicability in the context of GT engineering and
      characterization.

PMID- 21741953
TI  - Deoxyelephantopin from Elephantopus scaber L. induces cell-cycle arrest and
      apoptosis in the human nasopharyngeal cancer CNE cells.
AB  - Deoxyelephantopin (ESD), a naturally occurring sesquiterpene lactone present in
      the Chinese medicinal herb, Elephantopus scaber L. exerted anticancer effects on
      various cultured cancer cells. However, the cellular mechanisms by which it
      controls the development of the cancer cells are unavailable, particularly the
      human nasopharyngeal cancer CNE cells. In this study, we found that ESD inhibited
      the CNE cell proliferation. Cell cycle arrest in S and G2/M phases was also
      found. Western blotting analysis showed that modulation of cell cycle regulatory
      proteins was responsible for the ESD-induced cell cycle arrest. Besides, ESD also
      triggered apoptosis in CNE cells. Dysfunction in mitochondria was found to be
      associated with the ESD-induced apoptosis as evidenced by the loss of
      mitochondrial membrane potential (DeltaPsim), the translocation of cytochrome c,
      and the regulation of Bcl-2 family proteins. Despite the Western blotting
      analysis showed that both intrinsic and extrinsic apoptotic pathways (cleavage of
      caspases-3, -7, -8, -9, and -10) were triggered in the ESD-induced apoptosis,
      additional analysis also showed that the induction of apoptosis could be achieved
      by the caspase-independent manner. Besides, Akt, ERK and JNK pathways were found
      to involve in ESD-induced cell death. Overall, our findings provided the first
      evidence that ESD induced cell cycle arrest, and apoptosis in CNE cells. ESD
      could be a potential chemotherapeutic agent in the treatment of nasopharyngeal
      cancer (NPC).

PMID- 21741954
TI  - Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in
      disease.
AB  - A promising drug target currently under investigation to improve cognitive
      deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic
      alpha7 acetylcholine receptor (alpha7nAChR). Improving cognitive impairments in
      diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical
      need, and the alpha7nAChR has many properties that make it an attractive
      therapeutic target. The alpha7nAChR is a ligand gated ion channel that has
      particularly high permeability to Ca(2+) and is expressed in key brain regions
      involved in cognitive processes (e.g., hippocampus). The alpha7nAChRs are
      localized both pre-synaptically, where they can regulate neurotransmitter
      release, and post-synaptically where they can activate intracellular signaling
      cascades and influence downstream processes involved in learning and memory. In
      particular, activation of the alpha7nAChR with small molecule agonists enhances
      long-term potentiation, an in vitro model of synaptic plasticity, and improves
      performance across multiple cognitive domains in rodents, monkeys, and humans.
      Positive allosteric modulation of the alpha7nAChR offers an alternate approach to
      direct agonism that could prove to be particularly beneficial in certain disease
      populations where smoking nicotine is prevalent (e.g., schizophrenia) and could
      interfere with an orthosteric agonist approach. The current review focuses on the
      neurobiology of the alpha7nAChR, its role in cognition and the development status
      of some of the most promising molecules advancing for the treatment of cognitive
      dysfunction in disease.

PMID- 21741955
TI  - Asthma translational medicine: report card.
AB  - Over the last 30 years, scientific research into asthma has focused almost
      exclusively on one component of the disorder - airway inflammation - as being the
      key underlying feature. These studies have provided a remarkably detailed and
      comprehensive picture of the events following antigen challenge that lead to an
      influx of T cells and eosinophils in the airways. Indeed, in basic research, even
      the term "asthma" has become synonymous with a T helper 2 cell-mediated disorder.
      From this cascade of cellular activation processes and mediators that have been
      identified it has been possible to pinpoint critical junctures for therapeutic
      intervention, leading experimentalists to produce therapies that are very
      effective in decreasing airway inflammation in animal models. Many of these
      compounds have now completed early Phase 2 "proof-of-concept" clinical trials so
      the translational success of the basic research model can be evaluated. This
      commentary discusses clinical results from 39 compounds and biologics acting at
      23 different targets, and while 6 of these drugs can be regarded as a qualified
      success, none benefit the bulk of asthma sufferers. Despite this disappointing
      rate of success, the same immune paradigm and basic research models, with a few
      embellishments to incorporate newly identified cells and mediators, continue to
      drive target identification and drug discovery efforts. It is time to re-evaluate
      the focus of these efforts.

PMID- 21741956
TI  - Interplay between Ret and Fap-1 regulates CD95-mediated apoptosis in medullary
      thyroid cancer cells.
AB  - Emerging evidence suggests that Ret oncoproteins expressed in medullary thyroid
      cancer (MTC) might evade the pro-apoptotic function of the dependence receptor
      proto-Ret by directly impacting the apoptosis machinery. Identification of the
      molecular determinants of the interplay between Ret signaling and apoptosis might
      provide a relevant contribution to the optimization of Ret-targeted therapies.
      Here, we describe the cross-talk between Ret-M918T oncogenic mutant responsible
      for type 2B multiple endocrine syndrome (MEN2B), and components of death receptor
      mediated extrinsic apoptosis pathway. In the human MEN2B-type MTC cell line MZ
      CRC-1 expressing Ret-M918T, Ret was found associated with Fap-1, known as
      inhibitor of the CD95 death receptor trafficking to the cell membrane, and with
      procaspase-8, the initiator pro-form caspase in the extrinsic apoptosis pathway.
      Cell treatment with the anti-tumor Ret kinase inhibitor RPI-1 inhibited tyrosine
      phosphorylation of procaspase-8, likely inducing its local activation, followed
      by downregulation of both Ret and Fap-1, and translocation of CD95 into lipid
      rafts. According to the resulting increase of CD95 cell surface expression, the
      CD95 agonist antibody CH11 enhanced RPI-1-induced cell growth inhibition and
      apoptosis. RET RNA interference downregulated Fap-1 protein in MZ-CRC-1 cells,
      whereas exogenous RET-M918T upregulated Fap-1 in HEK293 cells. Overall, these
      data indicate that the Ret oncoprotein exerts opposing controls on Fap-1 and
      CD95, increasing Fap-1 expression and decreasing CD95 cell surface expression.
      The functional interplay of the Ret mutant with the extrinsic apoptosis pathway
      provides a mechanism possibly contributing to MTC malignant phenotype and a
      rational basis for novel therapeutic strategies combining Ret inhibitors and CD95
      agonists.

PMID- 21741957
TI  - Arsenic trioxide and radiation enhance apoptotic effects in HL-60 cells through
      increased ROS generation and regulation of JNK and p38 MAPK signaling pathways.
AB  - The induction of apoptotic cell death is a significant mechanism of tumor cells
      under the influence of radio-/chemotherapy, and resistance to these treatments
      has been linked to some cancer cell lines with a low propensity for apoptosis.
      The present study aimed to investigate the enhanced effects and mechanisms in
      apoptosis and the cycle distribution of HL-60 cells, a human leukemia cell line
      lacking a functional p53 protein, after combination treatment with arsenic
      trioxide (ATO) and irradiation (IR). Our results indicated that combined
      treatment led to increased cytotoxicity and apoptotic cell death in HL-60 cells,
      which was correlated with the activation of cdc-2 and increased expression of
      cyclin B, the induction of intracellular reactive oxygen species (ROS)
      generation, the loss of mitochondria membrane potential, and the activation of
      caspase-3. The combined treatment of HL-60 cells pre-treated with Z-VAD or NAC
      resulted in a significant reduction in apoptotic cells. In addition, activation
      of JNK and p38 MAPK may be involved in combined treatment-mediated apoptosis. The
      data suggest that a combination of IR and ATO could be a potential therapeutic
      strategy against p53-deficient leukemia cells.

PMID- 21741958
TI  - Effects of CYP inhibitors on precocene I metabolism and toxicity in rat liver
      slices.
AB  - We present a comprehensive in vitro approach to assessing metabolism-mediated
      hepatotoxicity using male Sprague-Dawley rat liver slices incubated with the well
      characterized hepatotoxicant, precocene I, and inhibitors of cytochrome P450
      (CYP) enzymes. This approach combines liquid chromatography mass spectrometry (LC
      MS) detection methods with multiple toxicity endpoints to enable identification
      of critical metabolic pathways for hepatotoxicity. The incubations were performed
      in the absence and presence of the non-specific CYP inhibitor, 1
      aminobenzotriazole (ABT) and isoform-specific inhibitors. The metabolite profile
      of precocene I in rat liver slices shares some features of the in vivo profile,
      but also had a major difference in that epoxide dihydrodiol hydrolysis products
      were not observed to a measurable extent. As examples of our liver slice
      metabolite identification procedure, a minor glutathione adduct and previously
      unreported 7-O-desmethyl and glucuronidated metabolites of precocene I are
      reported. Precocene I induced hepatocellular necrosis in a dose- and time
      dependent manner. ABT decreased the toxicity of precocene I, increased exposure
      to parent compound, and decreased metabolite levels in a dose-dependent manner.
      Of the isoform-specific CYP inhibitors tested for an effect on the precocene I
      metabolite profile, only tranylcypromine was noticeably effective, indicating a
      role of CYPs 2A6, 2C9, 2Cl9, and 2E1. With respect to toxicity, the order of CYP
      inhibitor effectiveness was
      ABT>diethyldithiocarbamate~tranylcypromine>ketoconazole. Furafylline and
      sulfaphenazole had no effect, while quinidine appeared to augment precocene I
      toxicity. These results suggest that rat liver slices do not reproduce the
      reported in vivo biotransformation of precocene I and therefore may not be an
      appropriate model for precocene I metabolism. However, these results provide an
      example of how small molecule manipulation of CYP activity in an in vitro model
      can be used to confirm metabolism-mediated toxicity.

PMID- 21741959
TI  - Differential detection of KRAS mutations in codons 12 and 13 with a modified loop
      hybrid (LH) mobility shift assay using an insert-type LH-generator.
AB  - BACKGROUND: The loop-hybrid mobility shift assay (LH-MSA) was previously
      developed for the rapid detection of the EGFR mutation L858R for predicting
      clinical responses to gefitinib in lung cancer. Recently, clinical importance of
      determining KRAS mutations has been demonstrated in colorectal tumors as tumors
      harboring mutated KRAS genes were not responsive to therapy with EGFR-targeted
      antibodies such as cetuximab. METHODS: We developed a new version of the LH-MSA
      using an insert-type LH generator that was capable of detecting all 12 KRAS
      mutations in codons 12 and 13. RESULTS: Feasibility evaluation was performed with
      this new LH-MSA on 215 colorectal cancer specimens. KRAS codon 12 mutations were
      detected in 23% specimens and codon 13 mutations in 6.5% specimens by LH-MSA at a
      rate better than by direct sequencing. CONCLUSIONS: Using the new method, the
      G13D mutation was readily distinguishable from other KRAS mutations in codon 12
      and, therefore, would be advantageous for clinical applications.

PMID- 21741960
TI  - Quantitation of HBV covalently closed circular DNA in micro formalin fixed
      paraffin-embedded liver tissue using rolling circle amplification in combination
      with real-time PCR.
AB  - BACKGROUND: The study aimed to develop an effective method to quantitate HBV
      covalently closed circular DNA (cccDNA) using small section of formalin fixed
      paraffin-embedded (FFPE) liver biopsy. METHODS: Plasmid-safe ATP-dependent DNase
      (PSAD)-treated samples were subjected to rolling circle amplification (RCA) prior
      to real-time PCR mediated by cccDNA-selective primers. Human beta-actin gene was
      used as a reference control. RESULTS: Compared to the classical method, i.e.,
      PSAD digestion+real-time PCR, introduction of RCA increased the lower limit of
      detection for about 2 logs with good inter- and intra-assay reproducibility. HBV
      cccDNA was detected in 91.5% (119/130) of the FFPE samples. The cccDNA levels
      (copy/cell) between FFPE liver tissues and fresh frozen counterpart tissues were
      comparable. The median of cccDNA level in HBeAg-positive patients was higher than
      that in HBeAg-negative ones (52.60 vs. 31.25copies/cell, P<0.01). Intrahepatic
      cccDNA level was positively correlated with intrahepatic HBV total DNA level, but
      not obviously correlated with serum HBV DNA or alanine aminotransferase levels.
      CONCLUSIONS: The method could sensitively and specifically quantitate
      intrahepatic HBV cccDNA in micro FFPE liver biopsy tissue for evaluation of HBV
      replication status in the liver.

PMID- 21741961
TI  - Vgll2a is required for neural crest cell survival during zebrafish craniofacial
      development.
AB  - Invertebrate and vertebrate vestigial (vg) and vestigial-like (VGLL) genes are
      involved in embryonic patterning and cell fate determination. These genes encode
      cofactors that interact with members of the Scalloped/TEAD family of
      transcription factors and modulate their activity. We have previously shown that,
      in mice, Vgll2 is differentially expressed in the developing facial prominences.
      In this study, we show that the zebrafish ortholog vgll2a is expressed in the
      pharyngeal endoderm and ectoderm surrounding the neural crest derived mesenchyme
      of the pharyngeal arches. Moreover, both the FGF and retinoic acid (RA) signaling
      pathways, which are critical components of the hierarchy controlling craniofacial
      patterning, regulate this domain of vgll2a expression. Consistent with these
      observations, vgll2a is required within the pharyngeal endoderm for NCC survival
      and pharyngeal cartilage development. Specifically, knockdown of Vgll2a in
      zebrafish embryos using Morpholino injection results in increased cell death
      within the pharyngeal arches, aberrant endodermal pouch morphogenesis, and
      hypoplastic cranial cartilages. Overall, our data reveal a novel non-cell
      autonomous role for Vgll2a in development of the NCC-derived vertebrate
      craniofacial skeleton.

PMID- 21741962
TI  - Distinct roles for classical nuclear import receptors in the growth of
      multinucleated muscle cells.
AB  - Proper muscle function is dependent on spatial and temporal control of gene
      expression in myofibers. Myofibers are multinucleated cells that are formed,
      repaired and maintained by the process of myogenesis in which progenitor
      myoblasts proliferate, differentiate and fuse. Gene expression is dependent upon
      proteins that require facilitated nuclear import, however little is known about
      the regulation of nucleocytoplasmic transport during the formation of myofibers.
      We analyzed the role of karyopherin alpha (KPNA), a key classical nuclear import
      receptor, during myogenesis. We established that five karyopherin alpha paralogs
      are expressed by primary mouse myoblasts in vitro and that their steady-state
      levels increase in multinucleated myotubes, suggesting a global increase in
      demand for classical nuclear import during myogenesis. We used siRNA-mediated
      knockdown to identify paralog-specific roles for KPNA1 and KPNA2 during
      myogenesis. KPNA1 knockdown increased myoblast proliferation, whereas KPNA2
      knockdown decreased proliferation. In contrast, no proliferation defect was
      observed with KPNA4 knockdown. Only knockdown of KPNA2 decreased myotube growth.
      These results identify distinct pathways involved in myoblast proliferation and
      myotube growth that rely on specific nuclear import receptors suggesting that
      regulation of classical nuclear import pathways likely plays a critical role in
      controlling gene expression in skeletal muscle.

PMID- 21741963
TI  - Cellular and molecular investigations into the development of the pectoral
      girdle.
AB  - The forelimbs of higher vertebrates are composed of two portions: the
      appendicular region (stylopod, zeugopod and autopod) and the less prominent
      proximal girdle elements (scapula and clavicle) that brace the limb to the main
      trunk axis. We show that the formation of the muscles of the proximal limb occurs
      through two distinct mechanisms. The more superficial girdle muscles (pectoral
      and latissimus dorsi) develop by the "In-Out" mechanism whereby migration of
      myogenic cells from the somites into the limb bud is followed by their extension
      from the proximal limb bud out onto the thorax. In contrast, the deeper girdle
      muscles (e.g. rhomboideus profundus and serratus anterior) are induced by the
      forelimb field which promotes myotomal extension directly from the somites. Tbx5
      inactivation demonstrated its requirement for the development of all forelimb
      elements which include the skeletal elements, proximal and distal muscles as well
      as the sternum in mammals and the cleithrum of fish. Intriguingly, the formation
      of the diaphragm musculature is also dependent on the Tbx5 programme. These
      observations challenge our classical views of the boundary between limb and trunk
      tissues. We suggest that significant structures located in the body should be
      considered as components of the forelimb.

PMID- 21741964
TI  - Coronary hemodynamic regulation by nitric oxide in experimental animals: recent
      advances.
AB  - Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles
      in the regulation of coronary blood flow through vasodilatation and decreased
      vascular resistance and in the inhibition of platelet aggregation and adhesion,
      leading to the prevention of coronary circulatory failure, thrombosis, and
      atherosclerosis. NO restrains myocardial oxygen consumption, when coronary
      perfusion is restricted. Endothelial function is impaired by pathogenic factors
      including smoking, excess salt intake, obesity, aging, hypercholesterolemia,
      hyperglycemia, and hypertension. The mechanisms involved in endothelial
      dysfunction are reduced NOS expression and activity, decreased NO
      bioavailability, and increased production of oxygen radicals and endogenous NOS
      inhibitors. NADPH oxidase, xanthine oxidase, and NOS uncoupling are involved in
      increased superoxide generation. Plasma levels of asymmetric dimethylarginine,
      the endogenous NOS inhibitor, are increased by an impairment of enzymatic
      degradation by dimethylarginine dimethylaminohydrolase and alanine-glyoxylate
      aminotransferase 2. Impairment of coronary arteriolar dilatation induced by
      perivascular nitrergic nerve activation is involved in decreased coronary blood
      flow. NO derived from nNOS singly or in combination with eNOS protects against
      serious myocardial injury through ischemic insults. Ischemia-induced iNOS
      upregulation contributes to myocardial contractile dysfunction. Preventive and
      therapeutic measures, such as improvement of life-style and treatment with
      therapeutic agents, to eliminate pathogenic factors for endothelial dysfunction
      or nNOS-derived NO deprivation would be quite important for the prophylaxis and
      minimizing the development of coronary artery disease.

PMID- 21741965
TI  - G protein coupled receptor specificity for C3a and compound 48/80-induced
      degranulation in human mast cells: roles of Mas-related genes MrgX1 and MrgX2.
AB  - Although human mast cells express G protein coupled receptors for the
      anaphylatoxin C3a, previous studies indicated that C3a causes mast cell
      degranulation, at least in part, via a C3a receptor-independent mechanism similar
      to that proposed for polycationic molecules such as compound 48/80. The purpose
      of the present study was to delineate the receptor specificity of C3a-induced
      degranulation in human mast cells. We found that C3a, a C3a receptor
      "superagonist" (E7) and compound 48/80 induced Ca(2+) mobilization and
      degranulation in a differentiated human mast cell line, LAD2. However, C3a and E7
      caused Ca(2+) mobilization in an immature mast cell line, HMC-1 but compound
      48/80 did not. We have previously shown that LAD2 cells express MrgX1 and MrgX2
      but HMC-1 cells do not. To delineate the receptor specificity for C3a and
      compound 48/80 further, we generated stable transfectants expressing MrgX1 and
      MrgX2 in a rodent mast cell line, RBL-2H3 cells. We found that compound 48/80
      caused degranulation in RBL-2H3 cells expressing MrgX1 and MrgX2 but C3a did not.
      By contrast, E7 activated RBL-2H3 cells expressing MrgX2 but not MrgX1. These
      findings demonstrate that in contrast to previous reports, C3a and compound 48/80
      do not use a shared mechanism for mast cell degranulation. It shows that while
      compound 48/80 utilizes MrgX1 and MrgX2 for mast cell degranulation C3a does not.
      It further reveals the novel finding that the previously characterized synthetic
      peptide, C3a receptor "superagonist" E7 activates human mast cells via two
      mechanisms; one involving the C3a receptor and the other MrgX2.

PMID- 21741966
TI  - Frondoside A inhibits human breast cancer cell survival, migration, invasion and
      the growth of breast tumor xenografts.
AB  - Breast cancer is a major challenge for pharmacologists to develop new drugs to
      improve the survival of cancer patients. Frondoside A is a triterpenoid glycoside
      isolated from the sea cucumber, Cucumaria frondosa. It has been demonstrated that
      Frondoside A inhibited the growth of pancreatic cancer cells in vitro and in
      vivo. We investigated the impact of Frondoside A on human breast cancer cell
      survival, migration and invasion in vitro, and on tumor growth in nude mice,
      using the human estrogen receptor-negative breast cancer cell line MDA-MB-231.
      The non-tumorigenic MCF10-A cell line derived from normal human mammary
      epithelium was used as control. Frondoside A (0.01-5 MUM) decreased the viability
      of breast cancer cells in a concentration- and time-dependent manner, with 50%
      effective concentration (EC50) of 2.5 MUM at 24h. MCF10-A cells were more
      resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5 MUM at 24
      h). In the MDA-MB-231 cells, Frondoside A effectively increased the sub-G1
      (apoptotic) cell fraction through the activation of p53, and subsequently the
      caspases 9 and 3/7 cell death pathways. In addition, Frondoside A induced a
      concentration-dependent inhibition of MDA-MB-231 cell migration and invasion. In
      vivo, Frondoside A (100 MUg/kg/dayi.p. for 24 days) strongly decreased the growth
      of MDA-MB-231 tumor xenografts in athymic mice, without manifest toxic side
      effects. Moreover, we found that Frondoside A could enhance the killing of breast
      cancer cells induced by the chemotherapeutic agent paclitaxel. These findings
      identify Frondoside A as a promising novel therapeutic agent for breast cancer.

PMID- 21741967
TI  - The histamine H4 receptor: targeting inflammatory disorders.
AB  - The discovery of the histamine H(4) receptor has added a new chapter to the
      century of extensive biogenic amine research. The human histamine H(4) receptor
      is mainly expressed in cells of the human immune system (e.g. mast cells,
      eosinophils, monocytes, dendritic cells, T cells) and mediates several effects on
      chemotaxis with numerous cell types. The distinct expression pattern and the
      immunomodulatory role highlight its physiological relevance in inflammatory and
      immunological processes. Inflammatory conditions, e.g. allergy, asthma and
      autoimmune diseases, were for a long time thought to be mainly mediated by
      activation of the histamine H(1) receptor subtype. However, in the treatment of
      diseases as chronic pruritus, asthma and allergic rhinitis the use of histamine
      H(1) receptor antagonists is unsatisfying. Selective H(4) receptor ligands and/or
      synergism of histamine H(1) and H(4) receptor modulation may be more effective in
      such pathophysiological conditions. Promising preclinical studies underline its
      role as an attractive target in the treatment of inflammatory and autoimmune
      disorders. Meanwhile, first histamine H(4) receptor antagonist has reached
      clinical phases for the treatment of respiratory diseases.

PMID- 21741968
TI  - Chromaffin cell transplant in spinal cord reduces secondary allodynia induced by
      formalin in the rat. Role of opioid receptors and alpha2-adrenoceptors.
AB  - In the present study, the effect of chromaffin cell transplant in the spinal cord
      was evaluated on formalin-induced mechanical secondary allodynia in the rat.
      Chromaffin cells were transplanted into the lumbar subarachnoid space before or
      after formalin injection. Subcutaneous formalin injection (50 MUl, 1%) produced
      long-lasting secondary allodynia in the ipsilateral and contralateral hind paws.
      Once secondary allodynia was established, treatment with chromaffin cells
      produced a significant reduction in the nociceptive behavior in both hind paws.
      The antiallodynic effect was time-dependent since it was observed 15 days after
      chromaffin cell transplants but not before. On the other hand, pre-treatment with
      chromaffin cells prevented the expression of secondary allodynia in both hind
      paws in the rat. Antiallodynic effect of chromaffin cells was reverted with the
      non-selective opioid receptor antagonist naltrexone and the non-selective
      alpha(2)-adrenoceptor antagonist rauwolscine. Clusters of viable chromaffin cells
      labeled with anti-tyrosine hydroxylase antibodies were observed in the retrieved
      transplants 15 days after transplant. These results establish the analgesic
      efficacy of intrathecal chromaffin cells on formalin-induced secondary allodynia.
      Our data suggest that chromaffin cells release neuroactive substances including
      opioid peptides and adrenergic amines that reduce secondary allodynia in rats
      through activation of their receptors.

PMID- 21741969
TI  - Differential effects of esculetin and daphnetin on in vitro cell proliferation
      and in vivo estrogenicity.
AB  - Esculetin (6,7-dihydroxycoumarin) and daphnetin (7,8-dihydroxycoumarin) are
      secondary metabolites of plants used in folk medicine. These compounds have
      showed great antiproliferative activity in several tumor cell lines and have been
      proposed as potential anticancer agents. However, the estrogenic potential of
      these two compounds has to date not been reported. The present study compared
      esculetin and daphnetin on the inhibition of cell proliferation and cell cycle
      progression of the MCF-7 estrogen-responsive human carcinoma cell line. In vivo
      and in vitro estrogenic activity for both compounds was also evaluated. Esculetin
      inhibited cell proliferation after 72 h exposure (IC50=193 +/- 6.6 MUM), while
      daphnetin evidenced inhibiting effects starting at 24-h exposure (72 h, IC50=73
      +/- 4.1 MUM). Both effects showed changes in cyclin D1 gene expression. In non
      estrogenic conditions (E-screening assay), esculetin produced biphasic response
      on proliferation of the MCF-7 cells; at 10(-8)-10(-6)M, concentrations induced
      proliferative effects as EC50=4.07 * 10(-9)M (E(2)=2.91 * 10(-12)M); at higher
      concentrations (10(-5)-10(-4)M), cell proliferation was inhibited. Relative
      proliferative effect at E(2) was 52% (E(2)=100), relative proliferative potency
      was 0.072 (E(2)=100). Additionally, esculetin tested in vivo showed estrogenic
      effects at 50-100mg/kg doses; relative uterotrophic effect at E(2) was 37%, with
      relative uterotrophic potency registered at 0.003. In contrast, daphnetin did not
      induce estrogenic effects in vitro or with in vivo models. The low estrogenic
      activity of esculetin could prove useful in postmenopausal therapy but not as a
      safe antitumor agent in estrogen-dependent tumors. Daphnetin-based
      antiproliferative selectivity with MCF-7 cells showed that daphnetin is a
      promising antitumoral agent also acting on estrogen dependent tumors.

PMID- 21741970
TI  - Characterization of capsaicin induced responses in mice vas deferens: evidence of
      CGRP uptake.
AB  - Calcitonin gene-related peptide (CGRP) is extensively distributed in primary
      afferent sensory nerves, including those innervating the genitourinary tract.
      Capsaicin can stimulate the release of CGRP from intracellular stores of these
      nerves, but this phenomenon has not been investigated in-depth in isolated
      preparations. The present study sets out to study and characterize the capsaicin
      as well as CGRP-induced responses in isolated mouse vas deferens. The effects of
      capsaicin and CGRP family of peptides were studied on electrically-induced twitch
      responses in the absence or presence of transient receptor potential cation
      channel vanilloid subfamily member 1 (TRPV1) antagonist and CGRP receptor
      antagonists. Twitch responses were attenuated by capsaicin (1nM-30nM) and CGRP
      family of peptides. The potency order was CGRP>intermedin-long
      (IMDL)~[Cys(Et)(2,7)]alphaCGRP~adrenomedullin
      (AM)>[Cys(ACM)(2,7)]alphaCGRP>amylin (AMY). These responses were disinhibited by
      the CGRP receptor antagonists and TRPV1 antagonists. The addition of CGRP
      receptor antagonists caused a transient potentiation of the twitch response and
      this potentiation was blocked by pretreatment with capsaicin and enhanced by
      incubation with exogenous CGRP. During the second consecutive cumulative
      concentration-response curve with capsaicin, the first phase of concentration
      response curve disappeared and this was partially restored when the mouse vas
      deferens was preincubated with CGRP, suggesting the uptake of exogenous CGRP by
      nerves. Besides showing capsaicin-induced CGRP releases this study shows that
      exogenous CGRP can be taken up in vas deferens and can be re-released. CGRP
      uptake will add another dimension in understanding the homeostasis of this
      neuropeptide.

PMID- 21741971
TI  - Regulation of homeostasis and oncogenesis in the intestinal epithelium by Ras.
AB  - Much of our current state of knowledge pertaining to the mechanisms controlling
      intestinal epithelial homeostasis derives from epidemiological, molecular
      genetic, cell biological, and biochemical studies of signaling pathways that are
      dysregulated during the process of colorectal tumorigenesis. Activating mutations
      in members of the RAS oncoprotein family play an important role in the
      progression of colorectal cancer (CRC) and, by extension, intestinal epithelial
      homeostasis. Mutations in K-RAS account for 90% of the RAS mutations found in
      CRC. As such, the study of RAS protein function in the intestinal epithelium is
      largely encompassed by the study of K-RAS function in CRC. In this review, we
      summarize the data available from genetically defined in vitro and in vivo models
      of CRC that aim to characterize the oncogenic properties of mutationally
      activated K-RAS. These studies paint a complex picture of a multi-functional
      oncoprotein that engages an array of downstream signaling pathways to influence
      cellular behaviors that are both pro- and anti-tumorigenic. While the complexity
      of K-RAS biology has thus far prevented a comprehensive understanding of its
      oncogenic properties, the work to date lays a foundation for the development of
      new therapeutic strategies to treat K-RAS mutant CRC.

PMID- 21741972
TI  - Interleukin-4 enhances trafficking and functional activities of GM-CSF-stimulated
      mouse myeloid-derived dendritic cells at late differentiation stage.
AB  - Mouse bone marrow-derived dendritic cells (BMDCs) are being employed as an
      important model for translational research into the development of DC-based
      therapeutics. For such use, the localization and specialized mobility of injected
      BMDCs within specific immune tissues are known to define their immunity and
      usefulness in vivo. In this study, we demonstrate that IL-4, a key driving factor
      for in vitro propagation and differentiation of BMDCs, when added during a late
      culture stage can enhance the in vivo trafficking activity of granulocyte
      macrophage colony-stimulating factor (GM-CSF)-induced BMDCs. It suggests that the
      temporal control of IL-4 stimulation during the in vitro generation of DCs
      drastically affects the DC trafficking efficiency in vivo. With this modification
      of IL-4 stimulation, we also show that much less cytokine was needed to generate
      BMDCs with high purity and yield that secrete a high level of cytokines and
      possess a good capacity to induce proliferation of allogeneic CD4+ T cells, as
      compared to the conventional method that uses a continuous supplement of GM-CSF
      and IL-4 throughout cultivation. These results provide us with an important know
      how for differentiation of BMDCs from myeloid stem cells, and for use of other
      immune cells in related medical or stem cell applications.

PMID- 21741973
TI  - The polyprotein allergens of nematodes (NPAs) - structure at last, but still
      mysterious.
AB  - We are engaged in structural and functional studies of several types of lipid
      binding protein that are only found in nematodes. Amongst these are the nematode
      polyprotein allergens (NPAs) and we now report the solution structure of ABA-1A
      (As-NPA-A1), the most repeated unit within the NPA array of Ascaris suum, which
      is almost identical in amino acid sequence to that of Ascaris lumbricoides. The
      protein forms a slightly flattened, compact, globular fold consisting of a long
      central helix that participates in two flanking helical bundles. Two pockets
      lined with apolar amino acid sidechains are apparent, one in the carboxy-terminal
      region of the protein, and another smaller one in the amino-terminal region. The
      former appears to be the main site of fatty acid binding, and the latter may have
      different, though possibly overlapping, ligand binding propensities. The
      structure of the binding sites indicates that lipid ligands are anchored within
      them with their hydrophobic tails oriented towards the core of the protein and
      their polar headgroups bound to charged sidechains at the mouth of the pockets.
      The three-dimensional architectures of the amino- and carboxy-terminal halves of
      ABA-1A are closely similar, thereby strengthening the long-suspected idea that
      the repeated units of NPAs themselves originate from an ancient duplication
      event.

PMID- 21741974
TI  - RNA interference-produced autoregulation of inducible nitric oxide synthase
      expression.
AB  - Vector-mediated delivery of short-hairpin RNA (shRNA) to regulate gene expression
      holds a great therapeutic promise. We hypothesize that gene expression can be
      autoregulated with RNA interference. We used inducible nitric oxide synthase
      (iNOS) as a gene model to test this hypothesis. Lipopolysaccharide dose
      dependently increased iNOS in rat aortic smooth muscle cells and the nitrite
      production from these cells. These increases were attenuated in cells transfected
      with plasmids containing code for iNOS shRNA whose expression was controlled by
      an iNOS promoter. The production of shRNA was lipopolysaccharide dose-dependent.
      The lipopolysaccharide-induced iNOS expression in rat C6 glioma cells also was
      attenuated by transfection with plasmids containing the iNOS shRNA code. These
      results provide proof-of-concept evidence for using RNA interference technique to
      achieve autoregulation of gene expression.

PMID- 21741975
TI  - Spontaneous C-cleavage of a mini-intein without its conserved N-terminal motif A.
AB  - Previously, the C-terminal fragment of a split intein was known to undergo
      controllable C-cleavage at its C-terminus only when the N-terminal fragment of
      the intein was added. Here we constructed a similar split intein from the Ssp
      DnaX intein, but we unexpectedly observed that its C-terminal 136-aa fragment
      could undergo spontaneous C-cleavage without the N-terminal fragment that was up
      to 15 aa long and contained the conserved intein motif A. This C-cleavage
      activity was significantly decreased by a mutation of the conserved Thr residue
      in the conserved intein motif B. These findings suggest a robust intein structure
      in the absence of motif A and a larger role of motif B in the third step of the
      protein splicing mechanism.

PMID- 21741976
TI  - Asparagine 405 of heparin lyase II prevents the cleavage of glycosidic linkages
      proximate to a 3-O-sulfoglucosamine residue.
AB  - Heparin and heparan sulfate contain a rare 3-O-sulfoglucosamine residue critical
      for anticoagulation and virus recognition, respectively. The glycosidic linkage
      proximate to this 3-O-sulfoglucosamine is resistant to cleavage by all heparin
      lyases (Heps). HepII has a broad specificity. The crystal structure of the wild
      type HepII identified its active site and showed a close spatial proximity
      between Asn405 and the 3-OH group of the bound glucosamine residue. In this
      study, we mutated Asn405 to the less sterically demanding Ala405 or Gly405, which
      broadened the substrate specificity of HepII and caused it to cleave the
      resistant linkage proximate to the 3-O-sulfoglucosamine residue.

PMID- 21741977
TI  - Dopamine and mesotocin neurotransmission during the transition from incubation to
      brooding in the turkey.
AB  - We investigated the neuroendocrine changes involved in the transition from
      incubating eggs to brooding of the young in turkeys. Numbers of mesotocin (MT;
      the avian analog of mammalian oxytocin) immunoreactive (ir) neurons were higher
      in the nucleus paraventricularis magnocellularis (PVN) and nucleus supraopticus,
      pars ventralis (SOv) of late stage incubating hens compared to the layers. When
      incubating and laying hens were presented with poults, all incubating hens
      displayed brooding behavior. c-fos mRNA expression was found in several brain
      areas in brooding hens. The majority of c-fos mRNA expression by MT-ir neurons
      was observed in the PVN and SOv while the majority of c-fos mRNA expression in
      dopaminergic (DAergic) neurons was observed in the ventral part of the nucleus
      preopticus medialis (POM). Following intracerebroventricular injection of DA or
      oxytocin (OT) receptor antagonists, hens incubating eggs were introduced to
      poults. Over 80% of those injected with vehicle or the D1 DA receptor antagonist
      brooded poults, while over 80% of those receiving the D2 DA receptor antagonist
      or the OT receptor antagonist failed to brood the poults. The D2 DA/OT antagonist
      groups also displayed less c-fos mRNA in the dorsal part of POM and the medial
      part of the bed nucleus of the stria terminalis (BSTM) areas than did the D1
      DA/vehicle groups. These data indicate that numerous brain areas are activated
      when incubating hens initially transition to poult brooding behavior. They also
      indicate that DAergic, through its D2 receptor, and MTergic systems may play a
      role in regulating brooding behaviors in birds.

PMID- 21741978
TI  - Flow cytometric analysis of cytokine expression in short-term allergen-stimulated
      T cells mirrors the phenotype of proliferating T cells in long-term cultures.
AB  - BACKGROUND: Allergen-specific T(H) cells play an important role in IgE-mediated
      disorders as allergies. Since this T(H) cell-population only accounts for a small
      percentage of T(H) cells, they are difficult to phenotype without prior selection
      or expansion. METHODS: Grass-pollen-specific T(H) cell profiles were evaluated in
      5 allergic and 4 non-allergic individuals using three different approaches: CD154
      expression on ex vivo grass-pollen-activated PBMCs (i); CFSE-dilution in grass
      pollen-restimulated PBMCs (ii) and T cell lines enriched for allergen-specific T
      cells (iii). RESULTS: Relatively low numbers of allergen-specific T(H) cells were
      detected using CD154 expression, limiting the power to detect phenotypic
      differences between allergic and non-allergic individuals. In contrast, higher
      frequencies of proliferating T(H) cells were detected by loss-of-CFSE intensity
      in PBMCs and TCLs after grass-pollen-stimulation, resulting in the detection of
      significantly more IL-4 producing T(H) cells in allergic vs non-allergic
      individuals. In addition, higher numbers of IFNgamma producing T(H) cells were
      detected in long-term cultures compared to the CD154 expressing T(H) cells.
      CONCLUSION: To detect allergen-specific T(H) cells for a common allergen as grass
      pollen, expansion is not absolutely necessary, although within 8-day grass-pollen
      cultures, higher numbers of proliferating T(H) cells resulted in increased
      statistical power to detect phenotypic differences. However, this approach also
      detects more bystander activated T(H) cells. TCLs resulted in comparable
      percentages of cytokine expressing T cells as 8-day cultures. Therefore
      enrichment can be necessary for detection of T(H) cells specific for a single
      allergen or allergen-derived peptides, but is dispensable for the detection and
      phenotyping of allergen-specific T(H) cells using crude extracts.

PMID- 21741979
TI  - A hydrogen bond regulates slow motions in ubiquitin by modulating a beta-turn
      flip.
AB  - Proteins exist as conformational ensembles composed of multiple interchanging
      substates separated by kinetic barriers. Interconverting conformations are often
      difficult to probe, owing to their sparse population and transient nature. Here,
      we report the identification and characterization of a subset of conformations in
      ubiquitin that participate in microsecond-to-millisecond motions in the amides of
      Ile23, Asn25, and Thr55. A novel side chain to the backbone hydrogen bond that
      regulates these motions has also been identified. Combining our NMR studies with
      the available X-ray data, we have unearthed the physical process underlying slow
      motions-the interconversion of a type I into a type II beta-turn flip at residues
      Glu51 through Arg54. Interestingly, the dominant conformer of wild-type ubiquitin
      observed in solution near neutral pH is only represented by about 22% of the
      crystal structures. The conformers generated as a result of the dynamics of the
      hydrogen bond appear to be correlated to ligand recognition by ubiquitin.

PMID- 21741980
TI  - cAMP-dependent protein kinase A selects the excited state of the membrane
      substrate phospholamban.
AB  - Phosphorylation of membrane proteins is a central regulatory and signaling
      mechanism across cell compartments. However, the recognition process and
      phosphorylation mechanism of membrane-bound substrates by kinases are virtually
      unknown. cAMP-dependent protein kinase A (PKA) is a ubiquitous enzyme that
      phosphorylates several soluble and membrane-bound substrates. In cardiomyocytes,
      PKA targets phospholamban (PLN), a membrane protein that inhibits the
      sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). In the unphosphorylated state, PLN
      binds SERCA, reducing the calcium uptake and generating muscle contraction. PKA
      phosphorylation of PLN at S16 in the cytoplasmic helix relieves SERCA inhibition,
      initiating muscle relaxation. Using steady-state kinetic assays, NMR
      spectroscopy, and molecular modeling, we show that PKA recognizes and
      phosphorylates the excited, membrane-detached R-state of PLN. By promoting PLN
      from a ground state to an excited state, we obtained a linear relationship
      between rate of phosphorylation and population of the excited state of PLN. The
      conformational equilibrium of PLN is crucial to regulate the extent of PLN
      phosphorylation and SERCA inhibition.

PMID- 21741982
TI  - Experimental depression induces renal oxidative stress in rats.
AB  - Depression has been associated to inflammatory and oxidative events. Previous
      report has shown renal oxidative stress in patients with depression. In order to
      analyze if depressive status is related to renal oxidative and inflammatory
      events, Sprague Dawley rats were submitted to forced swimming test (FST) and the
      renal oxidative metabolism, monocyte-macrophage infiltration and Angiotensin II
      (Ang II) expression were determined. Rats were submitted to FST daily (30 min)
      for 15 days. Motor activity was analyzed before FST. Kidney sections were
      homogenized to measure nitric oxide (NO), malondialdehyde (MDA), reduced
      glutathione (GSH) and catalase activity by enzymatic and biochemical methods.
      Renal frozen sections were studied for superoxide anion (O2-),
      monocyte/macrophage infiltration and Ang II expression by histochemical and
      immunofluorescence methods. In addition, three groups of FST rats were treated
      with losartan, sertraline or water for 18 days with further renal O2-analysis. In
      the FST group, struggle time, motor activity, food intake and body weight gain
      were found decreased. Increased number of glomerular, interstitial and tubular O2
      positive cells was observed in FST rats. High renal content of nitrite/nitrate
      (NO), MDA and decreased amount of GSH were found in FST rats. Values of renal ED
      1 or Ang II positive cells in FST rats remained similar to controls; however, AT1
      receptor blocking (losartan) and sertraline reduced both depressive-like behavior
      and renal O2-expression. These data suggests that depression-like behavior in
      rats is involved in kidney oxidative stress probably mediated by AT1 receptors.

PMID- 21741981
TI  - Epistasis analysis between homologous recombination genes in Saccharomyces
      cerevisiae identifies multiple repair pathways for Sgs1, Mus81-Mms4 and RNase H2.
AB  - The DNA repair genes SGS1 and MUS81 of Saccharomyces cerevisiae are thought to
      control alternative pathways for the repair of toxic recombination intermediates
      based on the fact that sgs1Delta mus81Delta synthetic lethality is suppressed in
      the absence of homologous recombination (HR). Although these genes appear to
      functionally overlap in yeast and other model systems, the specific pathways
      controlled by SGS1 and MUS81 are poorly defined. Epistasis analyses based on DNA
      damage sensitivity previously indicated that SGS1 functioned primarily downstream
      of RAD51, and that MUS81 was independent of RAD51. To further define these
      genetic pathways, we carried out a systematic epistasis analysis between the
      RAD52-epistasis group genes and SGS1, MUS81, and RNH202, which encodes a subunit
      of RNase H2. Based on synthetic-fitness interactions and DNA damage
      sensitivities, we find that RAD52 is epistatic to MUS81 but not SGS1. In
      contrast, RAD54, RAD55 and RAD57 are epistatic to SGS1, MUS81 and RNH202. As
      expected, SHU2 is epistatic to SGS1, while both SHU1 and SHU2 are epistatic to
      MUS81. Importantly, loss of any RNase H2 subunit on its own resulted in increased
      recombination using a simple marker-excision assay. RNase H2 is thus needed to
      maintain genome stability consistent with the sgs1Delta rnh202Delta synthetic
      fitness defect. We conclude that SGS1 and MUS81 act in parallel pathways
      downstream of RAD51 and RAD52, respectively. The data further indicate these
      pathways share common components and display complex interactions.

PMID- 21741983
TI  - Arecoline augments cellular proliferation in the prostate gland of male Wistar
      rats.
AB  - Areca nut chewing is the fourth most popular habit in the world due to its
      effects as a mild stimulant, causing a feeling of euphoria and slightly
      heightened alertness. Areca nuts contain several alkaloids and tannins, of which
      arecoline is the most abundant and known to have several adverse effects in
      humans, specially an increased risk of oral cancer. On evaluating the effects of
      arecoline on the male endocrine physiology in Wistar rats, it was found that
      arecoline treatment led to an overall enlargement and increase in the wet weight
      of the prostate gland, and a two-fold increase in serum gonadotropin and
      testosterone levels. Since the prostate is a major target for testosterone, the
      consequences of arecoline consumption were studied specifically in the prostate
      gland. Arecoline treatment led to an increase in the number of rough endoplasmic
      reticulum and reduction of secretory vesicles, signifying a hyperactive state of
      the prostate. Increased expression of androgen receptors in response to arecoline
      allowed for enhanced effect of testosterone in the prostate of treated animals,
      which augmented cell proliferation, subsequently confirmed by an increase in the
      expression of Ki-67 protein. Cellular proliferation was also the outcome of
      concomitant over expression of the G(1)-to-S cell cycle regulatory proteins,
      cyclin D1 and CDK4, both at the transcriptional and translational levels. Taken
      together, the findings provide the first evidence that regular use of arecoline
      may lead to prostatic hyperplasia and hypertrophy, and eventually to disorders
      associated with prostate enlargement.

PMID- 21741984
TI  - Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory
      effect of antimicrobial triclocarban in a murine model.
AB  - The increasing use of the antimicrobial triclocarban (TCC) in personal care
      products (PCPs) has resulted in concern regarding environmental pollution. TCC is
      a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs)
      are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal
      models. However, the in vivo effects anticipated from a sEHI have not been
      reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of
      TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged
      murine model. Systolic blood pressure, plasma levels of several inflammatory
      cytokines and chemokine, and metabolomic profile of plasma oxylipins were
      determined. TCC significantly reversed LPS-induced morbid hypotension in a time
      dependent manner. TCC significantly repressed the increased release of
      inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC
      significantly shifted the oxylipin profile in vivo in a time-dependent manner
      towards resolution of inflammation as expected from a sEHI. These results
      demonstrated that at the doses used TCC is anti-inflammatory in the murine model.
      This study suggests that TCC may provide some benefits in humans in addition to
      its antimicrobial activities due to its potent inhibition of sEH. It may be a
      promising starting point for developing new low volume high value applications of
      TCC. However these biological effects also caution against the general over use
      of TCC in PCPs.

PMID- 21741985
TI  - Experiment-model interaction for analysis of epicardial activation during human
      ventricular fibrillation with global myocardial ischaemia.
AB  - We describe a combined experiment-modelling framework to investigate the effects
      of ischaemia on the organisation of ventricular fibrillation in the human heart.
      In a series of experimental studies epicardial activity was recorded from 10
      patients undergoing routine cardiac surgery. Ventricular fibrillation was induced
      by burst pacing, and recording continued during 2.5 min of global cardiac
      ischaemia followed by 30 s of coronary reflow. Modelling used a 2D description of
      human ventricular tissue. Global cardiac ischaemia was simulated by (i) decreased
      intracellular ATP concentration and subsequent activation of an ATP sensitive K+
      current, (ii) elevated extracellular K+ concentration, and (iii) acidosis
      resulting in reduced magnitude of the L-type Ca2+ current I(Ca,L). Simulated
      ischaemia acted to shorten action potential duration, reduce conduction velocity,
      increase effective refractory period, and flatten restitution. In the model,
      these effects resulted in slower re-entrant activity that was qualitatively
      consistent with our observations in the human heart. However, the flattening of
      restitution also resulted in the collapse of many re-entrant waves to several
      stable re-entrant waves, which was different to the overall trend we observed in
      the experimental data. These findings highlight a potential role for other
      factors, such as structural or functional heterogeneity in sustaining wavebreak
      during human ventricular fibrillation with global myocardial ischaemia.

PMID- 21741986
TI  - Morphine sensitization as a model of mania: comparative study of the effects of
      repeated lithium or carbamazepine administration.
AB  - Repeated unavoidable stress induces in rats decreased reactivity to avoidable
      stressors and an anhedonia-like condition that are reverted by long-term
      antidepressant treatments and regarded as models of core symptoms of depression.
      Morphine-sensitized rats present resilience to stress-induced behavioral deficits
      and, if hyporeactivity to stress models a depressive symptom, stress resistance
      can be regarded as a manic symptom. This hypothesis is supported by the
      observation that long-term lithium administration reinstates sensitivity to
      stress in sensitized rats. The first aim of the study was to examine the effects
      of carbamazepine, a standard antimanic treatment, on the stress resilience of
      sensitized rats, to further characterize morphine sensitization as a model of
      manic symptom. Carbamazepine administration abolished stress resilience but did
      not interfere with the expression of sensitization. The second aim of the study
      was to assess whether repeated carbamazepine treatment affected the dopaminergic
      and behavioral responses to a natural reward, a palatable food (vanilla sugar,
      VS), in non food-deprived sensitized and control rats and compare these possible
      effects with those of repeated lithium administration. Control and sensitized
      rats showed increased extraneuronal dopamine levels in the nucleus accumbens
      shell after VS consumption and competence to acquire an instrumental VS-sustained
      appetitive behavior (VAB). Repeated carbamazepine treatment abolished the
      dopaminergic response to VS consumption and disrupted the competence to acquire
      VAB in control rats. Lithium-treated rats showed a dopaminergic response to VS
      and easily acquired the appetitive behavior. In sensitized rats, neither
      carbamazepine nor lithium administration interfered with the dopaminergic
      response to VS and the acquisition of VAB. In summary, the effect of
      carbamazepine on the stress resilience of sensitized rats further supported the
      hypothesis that morphine sensitization might model some symptoms of mania.
      Moreover, in control rats carbamazepine treatment elicited an anhedonia-like
      condition that clearly distinguished the effects of this drug from those of
      lithium.

PMID- 21741987
TI  - Role of the ecto-nucleotidases in the cooperative effect of adenosine and
      neuropeptide-S on locomotor activity in mice.
AB  - Activation of adenosine receptors modifies the action of classic
      neurotransmitters (i.e. dopamine, glutamate and acetylcholine) and other
      neuromodulators, like vasoactive intestinal peptide (VIP), calcitonin gene
      related peptide (CGRP) and neuropeptide S (NPS). Similarly to adenosine, NPS is
      involved in the regulation of stimulus and response to fear and arousal. Thus,
      the present study investigates the effects of NPS on locomotor activity in mice
      treated with or without alpha,beta-methylene adenosine 5'-diphosphate (AOPCP),
      the inhibitor of ecto-5'-nucleotidase. Additionally, we evaluate the activity of
      ecto-5'-nucleotidase in brain slices of mice treated with or without NPS. Male
      adult CF-1 mice received i.c.v. NPS as 0.1 nmol injection with or without pre
      treatment with 1 nmol alpha,beta-methylene adenosine 5'-diphosphate (AOPCP), the
      selective inhibitor of ecto-5'-nucleotidase, to evaluate locomotor activity. In
      another set of experiments, mice received i.c.v. infusion of 0.1 nmol NPS to
      assay enzymatic activity in brain slices. The results demonstrated that the pre
      treatment with AOPCP, which was inactive per se, prevented NPS-induced
      hyperlocomotion in mice. The dose of 0.1 nmol NPS was efficient to induce
      hyperlocomotion in animals during the observation period in the activity cage.
      Regarding enzymatic activity, i.c.v. NPS injection did not induce any significant
      alterations in ATP and AMP hydrolysis in striatum and hippocampus brain slices of
      mice. The present study shows that the hyperlocomotor effect of NPS depends on
      the ecto-5'-nucleotidase activity.

PMID- 21741988
TI  - Melatonin protects against neurobehavioral and mitochondrial deficits in a
      chronic mouse model of Parkinson's disease.
AB  - Neuronal oxidative stress and mitochondrial dysfunction have been implicated in
      Parkinson's disease. Melatonin is a natural antioxidant and free radical
      scavenger that has been shown to effectively reduce cellular oxidative stress and
      protect mitochondrial functions in vitro. However, whether melatonin is capable
      of slowing down the neurodegenerative process in animal models of Parkinson's
      disease remains controversial. In this research, we examined long-term melatonin
      treatment on striatal mitochondrial and dopaminergic functions and on animal
      locomotor performance in a chronic mouse model of Parkinson's disease originally
      established in our laboratory by gradually treating C57BL/6 mice with 10 doses of
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (15 mg/kg, s.c.) and probenecid (250
      mg/kg, i.p.) over five weeks. We report here that when the chronic Parkinsonian
      mice were pre-treated and continuously treated with melatonin (5mg/kg/day, i.p.)
      for 18 weeks, the defects of mitochondrial respiration, ATP and antioxidant
      enzyme levels detected in the striatum of chronic Parkinson's mice were fully
      preempted. Meanwhile, the striatal dopaminergic and locomotor deficits seen in
      the chronic Parkinson's mice were partially and significantly forestalled. These
      results imply that long-term melatonin is not only mitochondrial protective but
      also moderately neuronal protective in the chronic Parkinson's mice. Melatonin
      may potentially be effective for slowing down the progression of idiopathic
      Parkinson's disease and for reducing oxidative stress and respiratory chain
      inhibition in other mitochondrial disorders.

PMID- 21741989
TI  - Interactions between ACE inhibitors and classical antiepileptic drugs in the
      mouse maximal electroshock seizures.
AB  - This study evaluated the effect of two angiotensin-converting enzyme (ACE)
      inhibitors, enalapril and cilazapril, commonly used antihypertensive drugs, on
      the protective efficacy of the classical antiepileptics - carbamazepine (CBZ),
      phenytoin (PHT), valproate (VPA) and phenobarbital (PB). For this purpose, we
      used the maximal electroshock seizure (MES) test in mice. Additionally, adverse
      effects of combined treatment with ACE inhibitors and antiepileptic drugs in the
      passive avoidance task and chimney test were assessed. All drugs were
      administered intraperitoneally. Neither enalapril (10, 20 and 30 mg/kg) nor
      cilazapril (5, 10 and 20mg/kg) affected the threshold for electroconvulsions.
      Enalapril (30 mg/kg) but not cilazapril (20mg/kg), enhanced the protective action
      of VPA, decreasing its ED(50) value from 249.5 to 164.9 mg/kg (p<0.01). Free
      plasma (non-protein-bound) and total brain concentrations of VPA were not
      significantly influenced by enalapril. Therefore, the observed interaction could
      be pharmacodynamic in nature. The combinations of ACE inhibitors with other
      antiepileptics (CBZ, PHT, and PB) were ineffective in that their ED(50) values
      against MES were not significantly changed. Enalapril and cilazapril remained
      ineffective as regards memory retention in the passive avoidance task or motor
      performance in the chimney test. The current study suggests that there are no
      negative interactions between the studied ACE inhibitors and classical
      antiepileptic drugs. Enalapril was even documented to enhance the anticonvulsant
      activity of VPA.

PMID- 21741990
TI  - Effects of trehalose and sorbitol on the activity and structure of Pseudomonas
      cepacia lipase: spectroscopic insight.
AB  - The stability of enzymes with no reduction in their catalytic activity still
      remains a critical issue in industrial applications. Naturally occurring
      osmolytes are commonly used as protein stabilizers. In this study we have
      investigated the effects of sorbitol and trehalose on the structural stability
      and activity of Pseudomonas cepacia lipase (PCL), using UV-visible, circular
      dichroism (CD) and fluorescence spectroscopy. Surface plasmon resonance (SPR)
      technique was used to trace changes in the refractive index and dielectric
      constant of the environment. The results revealed that catalytic activity and
      intrinsic fluorescence intensity of PCL increased in the presence of both
      osmolytes. Far-UV CD spectra indicated that the protein has undergone some
      conformational changes upon interacting with these osmolytes. Increasing the
      concentration of sorbitol led to changes in the refractive index and consequently
      the dielectric constant of environment; whereas in the case of trehalose, such
      changes were not significant. Unfavorable interactions of trehalose with protein
      surface induced higher preferential exclusion from the enzyme-water interface
      than that of sorbitol. Results of this report could give further insights about
      the stabilization mechanism of osmolytes.

PMID- 21741991
TI  - Detection of new allotypic variants of bovine lambda-light chain constant regions
      in different cattle breeds.
AB  - In the cattle breeds German Black Pied (GBP), German Simmental (GS), Holstein
      Friesian (HF), Aubrac (A) three transcribed allotypic variants in isotype IGLC2
      and five allotypic variants in isotype IGLC3 were identified. Substitutions
      within the putative interface to CH1 at position 11 and 79 were noted. In
      IGLC2(b), K79E led to a charge conversion. In IGLC3(b) and IGLC3(c), the E79N
      replacement removed the charge while the T11K substitution resulted in a
      positively charged amino acid residue. In addition, D15 and T16 were found in
      IGLC2(c), IGLC3(b), and IGLC3(c). Substitutions located on the outer site of the
      molecule were observed in IGLC2(b) (V40, H45.5), IGLC2(c) (A1, V40, D77),
      IGLC3(b) (A1, D77, D109, P127), IGLC3(c) (A1, G45.5, D77, D109, P127), IGLC3(d)
      (D109), and IGLC3(e) (A1). Amino acid residues P83 (IGLC2(c), IGLC3(b),
      IGLC3(c)), N93 (IGLC2(b)), D93 (IGLC3(b)), and G93 (IGLC3(c)) were positioned in
      cavities but seemed to be accessible for solvents.

PMID- 21741992
TI  - Cholesterol metabolism in neurons and astrocytes.
AB  - Cells in the mammalian body must accurately maintain their content of
      cholesterol, which is an essential membrane component and precursor for vital
      signalling molecules. Outside the brain, cholesterol homeostasis is guaranteed by
      a lipoprotein shuttle between the liver, intestine and other organs via the blood
      circulation. Cells inside the brain are cut off from this circuit by the blood
      brain barrier and must regulate their cholesterol content in a different manner.
      Here, we review how this is accomplished by neurons and astrocytes, two cell
      types of the central nervous system, whose cooperation is essential for normal
      brain development and function. The key observation is a remarkable cell-specific
      distribution of proteins that mediate different steps of cholesterol metabolism.
      This form of metabolic compartmentalization identifies astrocytes as net
      producers of cholesterol and neurons as consumers with unique means to prevent
      cholesterol overload. The idea that cholesterol turnover in neurons depends on
      close cooperation with astrocytes raises new questions that need to be addressed
      by new experimental approaches to monitor and manipulate cholesterol homeostasis
      in a cell-specific manner. We conclude that an understanding of cholesterol
      metabolism in the brain and its role in disease requires a close look at
      individual cell types.

PMID- 21741993
TI  - Memantine prevents aluminum-induced cognitive deficit in rats.
AB  - Memantine, a noncompetitive NMDA receptor blocker, has been demonstrated to be
      neuroprotective against various neurotoxins. Aluminum, a well-known neurotoxin,
      has been suggested to be a contributing factor in Alzheimer's disease. In this
      study we investigated the possible effect of memantine on aluminum-induced
      cognitive impairment in rats. Rats were exposed to aluminum chloride
      (100mg/kg/day) and memantine (5, 10 and 20mg/kg/day) for 60 days. Cognitive
      functions were evaluated using three tests: Morris water maze, radial arm maze
      and passive avoidance tests. Results showed that memantine failed at low doses to
      have any significant influence on aluminum-induced memory deficit, but the
      20mg/kg dose was found to cause significant enhancement of memory in the aluminum
      exposed rats. This is the first study to demonstrate the protective role of
      memantine against aluminum-induced neuronal dysfunction. Biochemical and
      histological investigations are highly indicated to clarify the possible
      pharmacodynamic basis.

PMID- 21741994
TI  - Activation of corticotropin-releasing factor receptors from the basolateral or
      central amygdala increases the tonic immobility response in guinea pigs: an
      innate fear behavior.
AB  - The tonic immobility (TI) behavior is an innate response associated with extreme
      threat situations such as a predator attack. Several studies have provided
      evidence suggesting an important role for corticotropin-releasing factor (CRF) in
      the regulation of the endocrine system, defensive behaviors and behavioral
      responses to stress. TI has been shown to be positively correlated with the basal
      plasma levels of corticosterone. CRF receptors and neurons that are
      immunoreactive to CRF are found in many cerebral regions, especially in the
      amygdaloid complex. Previous reports have demonstrated the involvement of the
      basolateral amygdaloid (BLA) and central amygdaloid (CeA) nuclei in the TI
      response. In this study, we evaluated the CRF system of the BLA and the CeA in
      the modulation of the TI response in guinea pigs. The activation of CRF receptors
      in the BLA and in the CeA promoted an increase in the TI response. In contrast,
      the inhibition of these receptors via alpha-helical-CRF(9-41) decreased the
      duration of the TI response. Moreover, neither the activation nor inhibition of
      CRF receptors in the BLA or the CeA altered spontaneous motor activity in the
      open-field test. These data suggest that the activation of the CRF receptors in
      the BLA or the CeA probably potentiates fear and anxiety, which may be one of the
      factors that promote an increase in the TI behavior. Therefore, these data
      support the role of the CRF system in the control of emotional responses,
      particularly in the modulation of innate fear.

PMID- 21741995
TI  - Olfactory memory is impaired in a triple transgenic model of Alzheimer disease.
AB  - Olfactory memory dysfunctions were investigated in the triple-transgenic murine
      model of Alzheimer's disease (3 * Tg-AD). In the social transmission of food
      preference test, 3 * Tg-AD mice presented severe deficits in odor-based memory,
      without gross changes in general odor-ability. Abeta and tau immunoreactivity was
      not observed in the primary processing regions for odor, the olfactory bulbs
      (OBs), whereas marked immunostaining was present in the piriform, entorhinal, and
      orbitofrontal cortex, as well as in the hippocampus. Our results suggest that the
      impairment in olfactory-based information processing might arise from
      degenerative mechanisms mostly affecting higher cortical regions and limbic
      areas, such as the hippocampus.

PMID- 21741996
TI  - Rapid task acquisition of spatial-delayed alternation in an automated T-maze by
      mice.
AB  - The spatial-delayed alternation task using a T-maze is the standard method for
      testing working memory in rodents and is widely used. Until now, however, there
      has been a gap in the understanding of the underlying brain mechanisms. The
      development of new manganese-enhanced brain imaging methods now permit a more
      specific examination of these mechanisms by allowing behavioural brain
      stimulation to take place outside the MRI scanner and the scan identifying the
      activation of specific brain regions to take place subsequently. The requirements
      for this method are a frequent repetition of the behaviour of interest, a control
      group that differs in only one task parameter and the minimization of unspecific
      environmental factors to avoid irrelevant stimulation. To meet these
      requirements, a fully automated spatial-delayed alternation task in a T-maze was
      developed that used identity detectors and automated gates to route mice
      individually from their social home cage to the T-maze. An experimental and a
      control group of mice were trained in procedures that differed only in the
      parameter "working-memory based alternation". Our data demonstrate that both
      groups can be trained concurrently with a rapid procedure using the automated T
      maze. With its high level of stimulation, the minimization of unspecific
      stimulation through environmental factors and the simultaneous training of a
      control group that differs in only one task parameter our set-up and procedure
      met the requirements of new imaging techniques for the study of the influence of
      a specific cognitive component of spatial-delayed alternation on activity in
      specific brain regions.

PMID- 21741997
TI  - C/EBP zeta targets to neutrophil gelatinase-associated lipocalin (NGAL) as a
      repressor for metastasis of MDA-MB-231 cells.
AB  - Breast cancer is a leading cause of morbidity in women worldwide. neutrophil
      gelatinase-associated lipocalin (NGAL), a useful biomarker of ER negative (ER(-))
      breast cancer, promotes local tumor invasion and lymph node metastasis. We first
      identified the distinctive expression of NGAL in two breast cancer cell lines
      MCF7 and MDA-MB-231 cells, and then confirmed NGAL as a critical inducer of
      metastasis. Finally, the transcriptional factor CCAAT enhancer-binding proteins
      zeta (C/EBP zeta) was overexpressed in MDA-MB-231 cells. Consistent with the
      effect of NGAL knockdown, C/EBP zeta overexpression caused the significant
      changes that could prevent cell metastasis. C/EBP zeta overexpression induced a
      strong decrease in NGAL and matrix metalloproteinases (MMPs) expressions as
      determined by quantitative real time PCR and Western blotting. To identify the
      potential role of C/EBP zeta on regulating of NGAL in breast cancer, we
      established the dual-luciferase reporter assay for NGAL in MDA-MB-231 cells
      cotransfected with C/EBP zeta. Promoter reporter assays determined that C/EBP
      zeta directly repressed the human NGAL gene promoter activity by inhibiting the
      NGAL transcription. Taken together, this work identified that the C/EBP zeta
      overexpression downregulated NGAL to inhibit migration and invasion of breast
      cancer, which could be used as a novel strategy for breast cancer therapy.

PMID- 21741998
TI  - A rapid lateral-flow immunoassay for phytosanitary detection of Erwinia amylovora
      and on-site fire blight diagnosis.
AB  - Fire blight is an invasive disease caused by Erwinia amylovora that threatens
      pome fruit production globally. Effective implementation of phytosanitary control
      measures depends upon rapid, reliable pathogen detection and disease diagnosis.
      We developed a lateral-flow immunoassay specific for E. amylovora with a
      detection limit of log 5.7 CFU/ml, typical of pathogen concentrations in
      symptomatic plant material. The simple assay had comparable sensitivity to
      standard culture plating, serum agglutination and nested PCR when validated for
      application in a phytosanitary laboratory as a confirmatory test of cultured
      isolates and for first-line diagnosis of phytosanitary samples that represent the
      full range of commercial, ornamental and forestry host species. On-site
      validation in ring-trials with local plant inspectors demonstrated robust and
      reliable detection (compared to subsequent plating and PCR analysis). The
      simplicity, inspector acceptance and facilitation of expedited diagnosis (from 2
      days for laboratory submitted samples to 15 min with the immunoassay), offers a
      valuable tool for improved phytosanitary control of fire blight.

PMID- 21741999
TI  - Genotyping of the protozoan pathogen Toxoplasma gondii using high-resolution
      melting analysis of the repeated B1 gene.
AB  - Genetic studies of the protozoan parasite Toxoplasma gondii have identified three
      main distinct types according to virulence in some hosts. Several methods have
      been developed to differentiate genotypes currently dominated by microsatellite
      markers targeting single-copy loci. We analyzed the possibility of using the 35
      fold repetitive B1 gene via high-resolution melting (HRM) curve analysis.
      Sequencing of the B1 gene of 14 reference strains (four Type I, six Type II, and
      four Type III strains) identified 18 single nucleotide polymorphisms (SNP).
      Primers were designed to amplify eight of them for HRM analysis and for relative
      quantification of each nucleotide variation using SNaPshot mini-sequencing.
      Genotyping with five microsatellite markers was performed for comparison. Two to
      four HRM profiles were obtained depending on the SNP tested. The differences
      observed relied on the different ratios of nucleotides at the SNP locus as
      evidenced via SNaPshot mini-sequencing. The three main lineages could be
      distinguished by using several HRM profiles. Some HRM profiles proved more
      informative than the analysis based on five microsatellite markers, showing
      additional differences in Type I and Type II strains. Using HRM analysis, we
      obtained at least an equally good discrimination of the main lineages than that
      based on five microsatellite markers.

PMID- 21742000
TI  - IL-1 cytokine family members and NAFLD: neglected in metabolic liver
      inflammation.

PMID- 21742001
TI  - CD28 and KIR2D receptors as sensors of the immune status in heart and liver
      transplantation.
AB  - Viral infections and cellular acute rejection (AR) condition immunosuppressive
      therapy and compromise the evolution of allografts. Immune monitoring can be
      useful for ascertaining rejection and for differentiating allo-reaction from
      activation induced by infections. This work analyzes the usefulness of monitoring
      the expression of CD28 and KIR2D receptors in peripheral blood T lymphocytes by
      flow cytometry, to ascertain the immune response in heart and liver transplant
      recipients. In both types of transplant, the up-regulation of CD28 in CD4(+)
      lymphocytes in the periods of greatest AR frequency indicates an effective allo
      response, whereas the post-transplantation emergence of circulating CD8(+)CD28(-)
      and CD8(+)CD28(-)KIR2D(+) T cells correlates with better early clinical results.
      Cytomegalovirus (CMV) infection, but not hepatitis C virus (HCV) or other
      infections, abrogated both CD28 up-regulation and CD8(+)CD28(-)KIR2D(+) T-cell
      expansion. Our results show that monitoring the expression of CD28 and KIR2D
      receptors on T lymphocytes might be considered as sensors of the immune status of
      heart and liver recipients.

PMID- 21742002
TI  - Productive infection of human hepatocellular carcinoma cells by porcine
      circovirus type 1.
AB  - Porcine circovirus type 1 (PCV1), a small DNA virus in pigs, recently gained its
      notoriety when commercial human rotavirus vaccines were discovered to be
      contaminated by infectious PCV1. Here we report, for the first time, definitive
      evidence of productive PCV1 infection in a subclone of human hepatocellular
      carcinoma cell line (Huh-7, subclone 10-3). Infectious virus was detected in the
      lysates of infected Huh-7 cells by immunofluorescent assay (IFA) and can be
      serially passaged in Huh-7-S10-3 cells. The growth kinetic of PCV1 in Huh-7-S10-3
      cells was determined in a one-step growth curve using IFA and a quantitative PCR
      assay. PCV1 achieved a lower infectious titer in Huh-7-S10-3 human cells compared
      to the titer normally achieved in porcine PK-15 cells from published studies.
      While the direct relevance to vaccine safety of PCV1 growth in human
      hepatocellular carcinoma cells is unclear, these data should be considered in
      further evaluation of vaccines and other products that could contain infectious
      PCV1.

PMID- 21742003
TI  - Novel fusion protein protects against adherence and toxicity of enterohemorrhagic
      Escherichia coli O157:H7 in mice.
AB  - Infection with Escherichia coli (E. coli) O157:H7 may develop into bloody
      diarrhea, or hemorrhagic uremic syndrome (HUS), which usually causes kidney
      failure or even death. Considered as the pathogenesis mechanism of E. coli
      O157:H7 infection, attachment or adhesion that is directly mediated by intimin is
      the first step of E. coli O157:H7 interaction with its host, and all these
      serious sequelae are mainly due to Shiga toxins (Stxs) released by E. coli
      O157:H7. In this study, a novel SSI fusion protein that contains the critical
      toxin-antigens Stx2B and Stx1B, and the critical adhesion-antigen fragment Int281
      was constructed. The protein induced complete immune protection, with both anti
      toxin and anti-adhesion effects. The dominant increase in IgG1 and the high level
      of Th2-typical cytokine (IL-4 and IL-10) expression showed that SSI significantly
      induced Th2-mediated humoral immune response. In the mouse model, the SSI fusion
      protein not only elicited neutralizing antibodies against both Stx1 and Stx2
      toxins, but also induced a high level of anti-adhesion antibodies. The SSI
      immunized mice did not show any pathologic changes. SSI provides evident
      protection with two-time immunization against a highly lethal dose of E. coli
      O157:H7.

PMID- 21742004
TI  - Evaluation of serotype-specific pneumococcal IgG measurement using two different
      polysaccharides from ATCC and SSI Diagnostica.
AB  - Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and
      mortality especially in infants and elderly people. Pneumococcus capsular
      polysaccharide has been characterised and more than 90 different serotypes have
      been identified. Serotype-specific antibodies against the capsular polysaccharide
      are produced during infection. At present, many countries follow the WHO
      pneumococcal ELISA IgG measurement protocol, in which polysaccharides from ATCC
      are used as antigens. In recent years, serotype specific polysaccharides from
      different producers have been tested in pneumococcal antibody assay's. In this
      project, purified serotype specific pneumococcal antigens from SSI Diagnostica
      and from ATCC were compared. In general, the data showed that both types of
      polysaccharide could be used as antigens. Furthermore, the effect of adsorption
      using different combinations of adsorption procedures was tested, showing similar
      results using CWPSmulti or CWPS+22F.

PMID- 21742005
TI  - The immunogenicity of a novel A (H1N1) vaccine in HIV-infected children.
AB  - BACKGROUND: In October 2009, the United Kingdom Department of Health recommended
      vaccination of high-risk groups, including children with HIV, with a novel, oil
      in-water AS03(B) adjuvanted Influenza A (H1N1) vaccine (Pandemrix). There were no
      published data available regarding the immunogenicity of this vaccine in such
      children. OBJECTIVES: This study evaluated the immunogenicity of the adjuvanted
      Influenza A (H1N1) vaccine in HIV-infected children immunised according to
      national recommendations and assessed the impact of vaccination on individual CD4
      counts and HIV viral loads. METHODS: HIV-infected children attending outpatient
      appointments between 01 November and 31 December 2009 were offered two doses of
      H1N1 vaccine three weeks apart and a blood test before and 3 weeks after the
      second dose of vaccine. Serum antibody responses were determined by a
      haemagglutination inhibition (HAI) assay using standard methods. RESULTS: Of the
      39 children recruited for vaccination, 31 (median age 11.2, range 3.0-17.9 years)
      received both doses of vaccine and provided pre- and post-vaccination blood
      samples. Eight children (26%) had baseline HAI titres >= 1:32. After vaccination,
      29 children (94%, 95% CI, 78.6-99.2%) had HAI titres >= 1:32 (seroprotection), of
      whom 27 (87.1%, 95% CI, 70.1-96.4%) had also had a four-fold rise in titres
      (seroconversion). In the univariate analysis, post-vaccination geometric mean
      titres (GMTs) were higher among the 21 children receiving highly active anti
      retroviral therapy compared with the 10 treatment-naive children (GMT 406 [95% CI
      218-757] vs. 128 [49-336]; P=0.035), but this was no longer statistically
      significant when adjusted for prevaccine GMTs. There was no significant impact of
      vaccination on CD4+ T cell count or HIV viral load. CONCLUSION: The AS03(B)
      adjuvanted pandemic Influenza A (H1N1) vaccine is highly immunogenic and appears
      to be safe in HIV-infected children.

PMID- 21742006
TI  - A TLR2 agonist is a more effective adjuvant for a Chlamydia major outer membrane
      protein vaccine than ligands to other TLR and NOD receptors.
AB  - Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial
      pathogen in the World and there is an urgent need for a vaccine to prevent these
      infections. To determine what type of adjuvant can better enhance the
      immunogenicity of a Chlamydia vaccine, we formulated the recombinant major outer
      membrane protein (Ct-rMOMP) with several ligands for Toll-like receptors (TLR)
      and the nucleotide-binding oligomerization domain (NOD) including Pam(2)CSK(4)
      (TLR2/TLR6), Poly (I:C) (TLR3), monophosphoryl lipid A (TLR4), flagellin (TLR5),
      imiquimod R837 (TLR7), imidazoquinoline R848 (TRL7/8), CpG-1826 (TLR9), M-Tri
      (DAP) (NOD1/NOD2) and muramyldipeptide (NOD2). Groups of female BALB/c mice were
      immunized intramuscularly (i.m.) three times with the Ct-rMOMP and each one of
      those adjuvants. Four weeks after the last immunization the mice were challenged
      intranasally (i.n.) with 10(4)C. trachomatis mouse pneumonitis (MoPn) inclusion
      forming units (IFU). As negative antigen control, mice were immunized with the
      Neisseria gonorrhoeae recombinant porin B (Ng-rPorB) and the same adjuvants. As a
      positive vaccine control, mice were inoculated i.n. with 10(4)IFU of MoPn. The
      humoral and cell mediated immune responses were determined the day before the
      challenge. Following the challenge the mice were weighed daily and, at 10 days
      post-challenge (p.c.), they were euthanized, their lungs weighted and the number
      of IFU in the lungs counted. As determined by the IgG2a/IgG1 ratio in the sera,
      mice immunized with Ct-rMOMP+Pam(2)CSK(4) showed a strong Th2 biased humoral
      immune response. Furthermore, these mice developed a robust cellular immune
      response with high Chlamydia-specific T cell proliferation and levels of IFN
      gamma production. In addition, based on changes in body weight, weight of the
      lungs and number of IFU recovered from the lungs, the mice immunized with Ct
      rMOMP+Pam(2)CSK(4), were better protected against the i.n. challenge than any
      group of mice immunized with Ct-rMOMP and the other adjuvants. In conclusion,
      Pam(2)CSK(4) should be evaluated as a candidate adjuvant for a C. trachomatis
      vaccine.

PMID- 21742007
TI  - Tellurium tetrachloride and diphenyl ditelluride cause cytotoxicity in rat
      hippocampal astrocytes.
AB  - Tellurium tetrachloride (TeCl(4)) and diphenyl ditelluride (DPDT) cytotoxicity,
      was investigated in rat astrocytes. Concentrations of 0.24-250MUM (24h) were
      tested for viability using MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazolium bromide) and trypan blue exclusion. MTT showed significant decreases
      at all concentrations tested for both compounds. Significant decreases in
      viability were seen in 1.95-250MUM of DPDT and 0.97-250MUM of TeCl(4) with trypan
      blue exclusion. The LC(50) for both compounds was 62.5MUM. Light and scanning
      microscopy confirm toxicity observed at higher concentrations. Thiobarbituric
      acid reactive substances (TBARs) assay, TUNEL, cytochrome c and caspase release
      were carried out. No significant increase in TBARS with either agent was observed
      (15.625-62.5MUM). TUNEL and cytochrome c assays demonstrated apoptosis in TeCl(4)
      treated cells (31.25-125MUM). Non-apoptotic cells were observed in DPDT treated
      cells. Studies of caspase 3/7 and caspase 9 indicated increased activity in
      TeCl(4) but not in DPDT treated cells. Optical Emission Spectroscopy of DPDT and
      TeCl(4) treated cells demonstrated significant accumulation of elemental
      tellurium in all treatment groups (31.25-125MUM). We conclude that DPDT and
      TeCl(4) are cytotoxic to astrocytes. TeCl(4) treated cells die via the intrinsic
      apoptotic pathway. Accumulation of tellurium occurs with both compounds, but
      results in different mechanisms of cell death.

PMID- 21742008
TI  - Antibacterial effects of enniatins J(1) and J(3) on pathogenic and lactic acid
      bacteria.
AB  - Enniatins (ENs) are N-methylated cyclohexadepsipeptides, secondary metabolites
      produced by various species of the genus Fusarium. They are known to act as
      antifungal, antiyeast and antibacterial and to possess antiinsecticidal and
      phytotoxic properties. In this study we evaluated for the first time the
      antibiotic effect of pure fractions of EN J(1) and J(3) on several pathogenic
      strains and lactic acid bacteria. The ENs J(1) and J(3) were purified from the
      fermentation extract of Fusarium solani growth on solid medium of wheat kamut,
      using the technique of the low pressure liquid chromatography (LPLC) followed by
      a semipreparative liquid chromatography (LC). The purity and the structure of the
      isolated compound were confirmed by electrospray ionization-mass spectrometry
      study-linear ion trap (ESI-MS-LIT). The use of both chromatographic techniques
      have permitted to produce and purify 47mg of the En J(1) and 50mg of the EN J(3)
      with a mean purity of 98% completely characterized with the technique of the ESI
      MS-LIT. Microbial bioassay analyses were carried out by incubation in MRSA and
      TSA for acid lactic and pathogenic bacteria, respectively during 24h at 37
      degrees C. None of the tested strains were inhibited by a 1ng dose of EN J(1) and
      J(3). These compounds were only not effective against Listeria monocytogenes,
      Pseudomonas aeruginosa and Salmonella enteric. This study highlight ENs J(1) and
      J(3) could be potentially effective antibacterial agents against several
      pathogenic and lactic acid bacteria.

PMID- 21742009
TI  - Effects of the artificial sweetener sucralose on Daphnia magna and Americamysis
      bahia survival, growth and reproduction.
AB  - The artificial sweetener sucralose has been detected in municipal wastewater
      effluent and surface waters at concentrations ranging from ng/L to low MUg/L. Few
      chronic ecotoxicological data are available in the peer reviewed literature with
      respect to sucralose. To address this data gap, 21 d Daphnia magna and 28 d
      Americamysis bahia (mysid shrimp) studies were conducted to assess the effects of
      sucralose on the survival, growth and reproduction of these organisms.
      Concentrations ?1800mg/L resulted in no statistically significant reduction in D.
      magna survival or reproduction. Survival, growth and reproduction of mysid shrimp
      were unaffected by ?93mg/L sucralose. The no observable effect concentration
      (NOEC) and lowest observable effect concentration (LOEC) for the D. magna study
      were 1800 and >1800mg/L, respectively. The NOEC and LOEC for the mysid study were
      93 and >93mg/L, respectively. Collectively, these data suggest that the
      concentrations of sucralose detected in the environment are well below those
      required to elicit chronic effects in freshwater or marine invertebrates.

PMID- 21742010
TI  - Characterization of human nicotinate phosphoribosyltransferase: Kinetic studies,
      structure prediction and functional analysis by site-directed mutagenesis.
AB  - Nicotinate phosphoribosyltransferase (NaPRT, EC 2.4.2.11) catalyzes the
      conversion of nicotinate (Na) to nicotinate mononucleotide, the first reaction of
      the Preiss-Handler pathway for the biosynthesis of NAD(+). Even though NaPRT
      activity has been described to be responsible for the ability of Na to increase
      NAD(+) levels in human cells more effectively than nicotinamide (Nam), so far a
      limited number of studies on the human NaPRT have appeared. Here, extensive
      characterization of a recombinant human NaPRT is reported. We determined its
      major kinetic parameters and assayed the influence of different compounds on its
      enzymatic activity. In particular, ATP showed an apparent dual
      stimulation/inhibition effect at low/high substrates saturation, respectively,
      consistent with a negative cooperativity model, whereas inorganic phosphate was
      found to act as an activator. Among other metabolites assayed, including
      nucleotides, nucleosides, and intermediates of carbohydrates metabolism, some
      showed inhibitory properties, i.e. CoA, several acyl-CoAs, glyceraldehyde 3
      phosphate, phosphoenolpyruvate, and fructose 1,6-bisphosphate, whereas
      dihydroxyacetone phosphate and pyruvate exerted a stimulatory effect.
      Furthermore, in light of the absence of crystallographic data, we performed
      homology modeling to predict the protein three-dimensional structure, and
      molecular docking simulations to identify residues involved in the recognition
      and stabilization of several ligands. Most of these residues resulted universally
      conserved among NaPRTs, and, in this study, their importance for enzyme activity
      was validated through site-directed mutagenesis.

PMID- 21742011
TI  - Early neural development in vertebrates is also a matter of calcium.
AB  - The calcium (Ca(2+)) signaling pathways have crucial roles in development from
      fertilization through differentiation to organogenesis. In the nervous system,
      Ca(2+) signals are important regulators for various neuronal functions, including
      formation and maturation of neuronal circuits and long-term memory. However,
      Ca(2+) signals are mainly involved in the earliest steps of nervous system
      development including neural induction, differentiation of neural progenitors
      into neurons, and the neuro-glial switch. This review examines when and how
      Ca(2+) signals are generated during each of these steps with examples taken from
      in vivo studies in vertebrate embryos and from in vitro assays using embryonic
      and neural stem cells. Also discussed is the highly specific nature of the Ca(2+)
      signaling pathway and its interaction with the other signaling pathways involved
      in early neural development.

PMID- 21742012
TI  - Separate and combined effects of low dose ketamine and nicotine on behavioural
      and neural correlates of sustained attention.
AB  - Given the cognitive-promoting properties of the nicotinic acetylcholinergic
      receptor (nAChR) agonist, nicotine, the increased prevalence of smoke-inhaled
      nicotine in schizophrenia has been interpreted as an attempt to self-correct
      cognitive deficits, which have been particularly pronounced in the attentional
      domain. As glutamatergic abnormalities have been implicated in these attentional
      deficiencies, this study attempted to shed light on the separate and interactive
      roles of the N-methyl-d-aspartate receptor (NMDAR) and nAChR systems in the
      modulation of attention by investigating, in healthy volunteers, the separate and
      combined effects of nicotine and the NMDAR antagonist ketamine on neural and
      behavioural responses in a sustained attention task. In a randomized, double
      blind, placebo controlled study, performance and the P300 event-related brain
      potential (ERP) in a visual information processing (RVIP) task were examined in
      20 smokers and 20 non-smokers (both male and female). Assessment involved
      intravenous injection of a low subperceptual bolus dose (.04mg/kg) of ketamine or
      placebo, which was accompanied by acute treatment with nicotine (4mg) or placebo
      gum. Nicotine-enhanced attentional processing was most evident in nonsmokers,
      with both performance accuracy and P300 amplitude measures. Ketamine's
      detrimental effects on these behavioural and electrophysiologic measures were
      negatively moderated by acute nicotine, the synergistic effects being expressed
      differently in smokers and nonsmokers. These findings support the view that acute
      alterations and individual differences in nAChR function can moderate even subtle
      glutamatergic-driven cognitive deficiencies in schizophrenia and can be important
      therapeutic targets for treating cognitive impairments in schizophrenia.

PMID- 21742013
TI  - Functional interaction of bone morphogenetic protein and growth hormone releasing
      peptide in adrenocorticotropin regulation by corticotrope cells.
AB  - Mechanisms by which GHRP stimulates ACTH release in corticotrope cells were
      investigated using mouse corticotrope AtT20 cells by focusing on the biological
      activity of BMP-4. GHRP-2 increased ACTH and cAMP secretion by AtT20 cells;
      however, its effects were less potent than the effects of CRH. BMP-4 suppressed
      basal ACTH production and POMC transcription, and the inhibition of endogenous
      BMP receptor signaling led to an increase in ACTH production. Of note, BMP-4
      suppressed ACTH production and POMC-promoter activity induced by CRH more
      efficaciously than that induced by GHRP-2. BMP-4 had no significant effect on
      cAMP synthesis induced by CRH or GHRP-2. Stimulation with CRH, but not GHRP-2,
      activated ERK1/2, p38, SAPK/JNK and Akt phosphorylation, in which CRH-induced
      phosphorylation of ERK and p38 was suppressed by BMP-4. GHRP-2-induced ACTH
      secretion was not affected by inhibitors of ERK, p38 and Akt pathways, which
      effectively suppressed CRH-induced ACTH release. Blockage of the cAMP-PKA pathway
      reversed CRH- as well as GHRP-2-induced ACTH secretion. Furthermore, the
      inhibition of ERK and p38 significantly reduced cAMP synthesis induced by CRH but
      not by GHRP-2. Thus, CRH activates ACTH production through ERK and p38 pathways
      in addition to the cAMP-PKA pathway, which is also activated downstream of MAPK.
      On the other hand, GHRP-2-induced ACTH production was predominantly linked to the
      cAMP-PKA pathway. Moreover, CRH and GHRP-2 upregulated BMP receptor signaling,
      while BMP-4, CRH and GHRP-2 had no significant effect on the expression level of
      GHSR. In addition, GHRP-2 suppressed the expression of Smad7, which is an
      inhibitor of the BMP-Smad1/5/8 pathway. Collectively, the results revealed a
      functional interaction between GHRP-2 and BMP signaling, in which endogenous BMP
      may act as an autoregulatory system in controlling ACTH production.

PMID- 21742014
TI  - HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I
      signals in FRTL-5 cells.
AB  - Prolonged stimulation of FRTL-5 thyroid cells with cAMP-generating agents
      including thyroid-stimulating hormone (TSH) or cAMP analogues potentiates
      tyrosine phosphorylation of insulin receptor substrate (IRS)-2 triggered by
      insulin-like growth factor (IGF)-I, leading to enhancement of IGF-I-dependent
      proliferation. Because we identified HSP90 as an IRS-2-interacting protein, the
      roles of HSP90 in potentiation of IGF signals through IRS-2 were investigated. We
      found that prolonged dibutyryl cAMP treatment induced serine/threonine
      phosphorylation of IRS-2. Using a specific inhibitor of HSP90 chaperone activity,
      geldanamycin, or small interfering RNA against HSP90, we showed that HSP90
      mediates cAMP-induced serine/threonine phosphorylation of IRS-2. Furthermore,
      inhibition of HSP90 by geldanamycin during dibutyryl cAMP pretreatment of cells
      for 24h suppressed cAMP-dependent potentiation of tyrosine phosphorylation of IRS
      2 induced by IGF-I. Taking together, we conclude that HSP90 interacting with IRS
      2 mediates cAMP-dependent serine/threonine phosphorylation of IRS-2 via its
      chaperone activity, leading to potentiation of tyrosine phosphorylation of IRS-2
      induced by IGF-I.

PMID- 21742015
TI  - Capsaicin prevents the hyperalgesia induced by peripheral group I mGluRs
      activation.
AB  - Group 1 metabotropic glutamate receptors (mGluRs) are expressed in peripheral and
      central neural tissues and involved in peripheral and central sensitization in
      various pain models. However, there are limited reports that activation of
      peripheral group I mGluRs could evoke pain. Furthermore, any behavioral evidences
      could not be found out, showing what kind of afferent fibers are involved in
      peripheral mGluRs-mediated hyperalgesia. This study was undertaken to clarify
      whether peripherally injected group I mGluRs agonists could induce pain-related
      behaviors and capsaicin-sensitive afferent fibers might be involved in the
      hyperalgesia. To assess pain sensitivity, mechanical threshold for paw withdrawal
      response (PWT) was measured and number of spontaneous flinching behavior was
      counted. Intraplantar injection of group I mGluR agonist, (RS)-3,5
      dihydroxyphenylglycine (DHPG) and mGluR5 agonist, (RS)-2-chloro-5
      hydroxyphenyglycine (CHPG) immediately induced pain-like behaviors, such as
      decrease of PWT and increased number of flinchings. These agonists-induced pain
      like behaviors were blocked by group I mGluRs antagonist, (RS)-1-aminoindan-1,5
      dicarboxylic acid (AIDA) and mGluR5 antagonist, 2-methyl-6-(phenylethynyl)
      pyridine hydrochloride (MPEP). Perineural pretreatment of 1% capsaicin solution
      significantly reduced pain-related behaviors induced by DHPG and CHPG, proposing
      that capsaicin-sensitive primary afferent fibers could be responsible for the
      hyperalgesia induced by activation of peripheral group I mGluRs. This study
      presents the first behavioral evidence that peripheral group I mGluRs activation
      could induce spontaneous as well as mechanical hyperalgesia and capsaicin
      sensitive afferent fiber could be implicated the group I mGluR mediated
      hyperalgesia.

PMID- 21742016
TI  - Up-regulation of endothelial endothelin-1 expression prior to vasogenic edema
      formation in the rat piriform cortex following status epilepticus.
AB  - Endothelin-1 (ET-1) is one of potential factors to induce vasogenic edema
      formation, since exogenous ET-1 treatment decreases aquaporin 4 (AQP4) expression
      and increases chemokines induction. To identify the role of endogenous ET-1 in
      vasogenic edema formation, we examined the correlation between endogenous ET-1
      expression and vasogenic edema formation in the pirifom cortex following status
      epilepticus (SE). In the present study, SMI-71 (a brain-blood barrier marker)
      immunoreactivity was significantly reduced in blood vessels at 1 day after SE
      when vasogenic edema and neuronal damage were observed. ET-1 expression was up
      regulated in endothelial cells prior to reduction in SMI-71 immunoreactivity.
      Furthermore, ET-1 expressing endothelial cells showed the absence of SMI-71
      immunoreactivity. Increase in ET-1 expression was followed by reduced AQP4
      immunoreactivity prior to vasogenic edema formation. Only a few microglia showed
      monocyte chemotactic protein-1 (a chemokine induced by ET-1) outside vasogenic
      edema lesion. Taken together, our findings suggest that endothelial ET-1
      expression may contribute to SE-induced vasogenic edema formation via brain-blood
      barrier disruption at AQP4/MCP-1 independent manners.

PMID- 21742017
TI  - High-fat diet selectively protects against the effects of chronic social stress
      in the mouse.
AB  - Obesity and stress-related psychiatric disorders are frequently comorbid.
      However, our understanding of the relationship between diet, everyday life stress
      and psychiatric disorders is limited. Although the ability of stress to increase
      the likelihood to develop obesity and its comorbidities in a feed-forward loop
      has been studied there is a dearth of studies especially at the behavioural level
      investigating the feedback hypothesis, that is, the consequences of high-fat diet
      consumption on chronic stress-induced alterations. The effects of unpredictable
      chronic psychosocial stress on anxiety-like behaviour in the light-dark box,
      depressive-like behaviour in the forced swim test, hedonic behaviour in the
      female urine sniffing test and social avoidance in the social interaction test
      were investigated in a mouse model of diet-induced obesity. Changes in plasma
      levels of leptin, insulin and corticosterone were also assessed. A clear
      dissociation in behaviours was observed in mice subjected to diet-induced obesity
      coupled with chronic stress, with anxiety- and depressive-like behaviour observed
      in mice on a low- but not on a high-fat diet exposed to chronic social stress. On
      the other hand, social avoidance and anhedonic behaviour was present following
      stress independent of diet. Moreover, the effect of chronic stress in lowering
      leptin levels was most apparent in mice on a high-fat diet. Plasma insulin levels
      however where only decreased in mice on high- but not low-fat diet. In
      conclusion, long-term exposure to high-fat diet selectively and robustly protects
      against some of the behavioural sequelae of chronic unpredictable social
      stressors. These data show that there is a clear discrimination in the nature of
      stress-induced behavioural effects sensitive to protection by high-fat diet.
      Moreover, these results illustrate the strong influence of dietary components on
      stress-induced psychological factors and thereby emphasize the importance of the
      brain-gut-axis as a point of future therapeutic intervention.

PMID- 21742018
TI  - Co-expression studies of the orphan carrier protein Slc10a4 and the vesicular
      carriers VAChT and VMAT2 in the rat central and peripheral nervous system.
AB  - The orphan carrier protein Slc10a4 represents a novel member of the so-called
      "sodium-bile acid co-transporter family," SLC10. Slc10a4 has a close phylogenetic
      relationship with the liver bile acid carrier Ntcp (Slc10a1), but has no
      transport activity for bile acids. In a previous study Slc10a4 proved to be
      predominantly expressed in the rat brain, where it was localized within
      cholinergic neurons. However, whether this cholinergic expression pattern was
      exclusive for Slc10a4 and whether this protein might also be expressed in the
      peripheral nervous system or other peripheral organs, remained unclear.
      Therefore, in the present study we analyzed the expression of Slc10a4 in neuronal
      and non-neuronal rat tissues more systematically, employing immunofluorescence co
      localization studies of the vesicular acetylcholine transporter VAChT and the
      vesicular monoamine transporter VMAT2. The Slc10a4 protein was found to be widely
      expressed throughout structures of the CNS and peripheral nervous system. In
      addition to cholinergic neurons in the CNS, the retina, the neuromuscular
      junction and parasympathetic innervations, Slc10a4 was also localized in certain
      monoaminergic neurons and nerve fibers in the substantia nigra, the spinal cord
      and sympathetic innervations. Slc10a4 expression was also detected in granules of
      rat peritoneal and tissue mast cells using immunofluorescence and electron
      microscopy. Western blot and immunoprecipitation experiments with rat brain
      vesicle preparations revealed that the Slc10a4 protein was expressed in synaptic
      vesicles where it co-localized with synaptophysin, VAChT and VMAT2. This
      vesicular expression pattern was also shown in the rat adrenal pheochromocytoma
      cell line PC12 by immunofluorescence. Based on the findings of the present study
      we can speculate about the function of Slc10a4 as follows: (I) Slc10a4 could be a
      novel vesicular transporter for cholinergic and/or various monoaminergic
      neurotransmitters in the central and peripheral nervous system or (II) may be
      involved in the regulation of the synaptic vesicle sorting or exocytosis process.

PMID- 21742019
TI  - Changes in postnatal norepinephrine alter alpha-2 adrenergic receptor
      development.
AB  - Alpha-2 adrenergic receptors (A2AR) regulate multiple brain functions and are
      enriched in developing brain. Studies demonstrate norepinephrine (NE) plays a
      role in regulating brain maturation, suggesting it is important in A2AR
      development. To investigate this we employed models of NE absence and excess
      during brain development. For decreases in NE we used N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine hydrochloride (DSP4), a specific noradrenergic neurotoxin.
      Increased noradrenergic terminal density was produced by methylazoxymethanol
      acetate (MAM) treatment. A2AR density was assayed with [(3)H]RX821002
      autoradiography. DSP4 lesions on postnatal day (PND) 3 produce A2AR decreases in
      many regions by PND 5. A2AR recover to control levels by PND 15 and 25 and there
      is no further change in total receptor density. We also assayed A2AR in brains
      lesioned with DSP4 on PND 13, 23, 33 and 43 and harvested 22 days post-lesion.
      A2AR levels remain similar to control at each of these time points. We examined
      A2AR functionality and high affinity state with epinephrine-stimulated
      [(35)S]GTPgammaS and [(125)I]p-iodoclonidine autoradiography, respectively. On
      PND 25, control animals and animals lesioned with DSP4 on PND 3 have similar
      levels of [(35)S]GTPgammaS incorporation and no change in high affinity state.
      This is in contrast to increases in A2AR high affinity state produced by DSP4
      lesions of mature brain. We next investigated A2AR response to increases in
      norepinephrine levels produced by MAM. In contrast to DSP4 lesions, increasing NE
      results in a large increase in A2AR. Animals treated with MAM on gestational day
      14 had cortical [(3)H]RX821002 binding 100-200% greater than controls on PND 25,
      35, 45, 55 and 65. These data indicate that NE regulation of A2AR differs in
      developing and mature brain and support the idea that NE regulates A2AR
      development and this has long term effects on A2AR function.

PMID- 21742020
TI  - Cisplatin transiently up-regulates hHR23 expression through enhanced
      translational efficiency in A549 adenocarcinoma cells.
AB  - DNA-damaging agents are commonly used as anticancer therapeutics. Unfortunately,
      such drugs induced DNA damages as well as DNA repair are important in mediating
      drug resistance to cancer treatments. To evaluate changes in DNA repair proteins
      that occur in DNA damage agent treatment, we challenged human A549 lung
      adenocarcinoma cells with cisplatin. hHR23/RAD23, an accessory protein involved
      in nucleotide-excision repair (NER) at an early lesion-recognition step, was
      upregulated by cisplatin in a dose- and time-dependent manner. Upregulation of
      hHR23 expression by low-dose cisplatin was accompanied by an increase in p53,
      p21, and XPC protein levels. Importantly, knockdown of hHR23B by RNA interference
      decreased DNA repair activity, cell survival, and induction of p53 and XPC
      following treatment with cisplatin. Conversely, overexpression of hHR23B enhanced
      repair activity towards cisplatin-damaged DNA. Inhibition of MEK/ERK and
      phosphoinositide 3-kinase (PI3K)/AKT signaling pathways attenuated cisplatin
      induced hHR23 expression, indicating that these pathways are involved in the
      process. The increase in hHR23 protein expression mediated by MEK/ERK signaling
      was due to increased translational efficiency resulting from
      phosphorylation/activation of the translation-initiating factor eIF-4B. Taken
      together, these results suggest that cisplatin-induced increases in hHR23 levels
      are regulated by proliferative signaling pathways and important for DNA repair.

PMID- 21742021
TI  - A comparison of ram extrusion by single-holed and multi-holed dies for extrusion
      spheronisation of microcrystalline-based pastes.
AB  - The use of multi-holed dies as an alternative to single-holed dies for generating
      extrudates for spheronisation was investigated both in terms of extrusion and
      spheronisation performance. A model 45wt% microcrystalline cellulose (MCC)/water
      paste was employed in ram extrusion tests with square-ended dies with 1, 6, 33
      and 137 holes, all of diameter 1mm and length 2mm. The extrudates generated using
      the multi-holed dies yielded pellets with comparable sphericity to those using
      the single-holed die. Multi-holed dies could also be operated with lower paste
      flow rates before encountering liquid phase migration (LPM). The characteristic
      processing velocity for the onset of LPM was determined for each die
      configuration and supported the hypothesis that LPM was caused by suction
      effects. A simple model of the flow pattern in a lab-scale Fuji-Paudal frontal
      screen extruder is presented which yields estimates of velocities and shear rates
      involved in these devices. The pressure required to extrude the paste through
      multi-holed dies was compared with the model proposed by Benbow and co-workers.
      The paste rheology was characterised using the Benbow-Bridgwater approach,
      employing 1, 2 and 3mm diameter dies of various lengths. The Benbow et al. model
      under-predicted the observed extrusion pressure, which was attributed to its
      failure to account for the redundant work contribution in these complex flows.

PMID- 21742022
TI  - Potential of a Khaya ivorensis -Alstonia boonei extract combination as
      antimalarial prophylactic remedy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the combined stem barks of Khaya
      ivorensis A. Chev. (Meliaceae) and Alstonia boonei De Wild (Apocynaceae) has a
      history of use in traditional medicine of central Cameroon for malaria treatment
      but also for the prevention of the disease. AIM OF THE STUDY: The purpose of this
      investigation was to determine the antiplasmodial activity of Khaya ivorensis (K)
      and Alstonia boonei (A) preparations in the murine malaria model Plasmodium
      berghei/Anopheles stephensi, to estimate their prophylactic potential and to
      assess acute and sub-acute toxicity of the formulations prepared according to the
      traditional recipes. MATERIALS AND METHODS: Aqueous extracts from the stem-bark
      of the two plants were prepared and tested separately and in combination. BALB/c
      mice were treated for 9 days and challenged on day 3 by exposure to mosquitoes
      infected with Plasmodium berghei. Treatment doses ranged between 200 and
      400mg/kg/day, corresponding approximately to the dosage applied by traditional
      healers to cure malaria patients or prevent the disease. Parasitemia reduction in
      treated animals was calculated from Giemsa smear counts, of two replicate
      experiments. To estimate acute toxicity in terms of median lethal dose (LD50),
      geometrically increasing doses were administered to mice. Sub-acute toxicity of
      the herbal combination (KA) was investigated by administering the same doses as
      in the antiplasmodial activity test for a period of 14 days, followed by 14 days
      of recovery observation. Locomotor activity (Open Field Test), body weight, liver
      and kidney morphology were monitored. RESULTS: The combination KA was found to
      exhibit antiplasmodial activity in the murine malaria model. In mice treated with
      the combination remedy at a dosage of 200mg/kg/day, parasitemia values of 6.2% +/
      1.7 and 6.5% +/- 0.8 were recorded, compared to 10.8% +/- 1.3 and 12.0% +/- 4.0
      in controls (p<0.01). Doubling the dosage of the extracts did not significantly
      increase parasite suppression. When extracts of K and A were administered
      separately at a dosage of 400mg/kg, a reduction in parasitemia was still
      obtained, but it did not reach statistical significance. Toxicity studies yielded
      comforting results: the LD50 was estimated to be greater than 2779.5mg/kg.
      Moreover, mice exposed to the fourteen-day repeated-dose toxicity test (sub-acute
      toxicity test) did not display weight loss, liver or kidney morphological
      modifications, significant alterations in locomotor activity or any other sign of
      illness. CONCLUSION: The antiplasmodial activity and the wide dose interval
      between the therapeutic dosage and the toxic dosage exhibited by the KA herbal
      combination in the murine malaria model argue in favor of its use as an
      antimalarial prophylactic remedy. It remains to be demonstrated by human clinical
      trials whether the combination remedy, when taken by inhabitants during malaria
      transmission season, can reduce parasite density and lead to a reduction of
      malaria episodes in the community.

PMID- 21742023
TI  - Interaction of the natural anxiolytic Galphimine-B with serotonergic drugs on
      dorsal hippocampus in rats.
AB  - AIM OF THE STUDY: Galphimine-B (G-B) is a nor-seco triterpene with an anxiolytic
      like effect obtained from the plant species Galphimia glauca Cav. By means of a
      double blind clinical trial, it has been demonstrated that the extract from this
      plant, standardized in G-B content, possesses therapeutic effectiveness in
      patients with generalized anxiety. The mechanism of action of this compound
      remains unknown to date, but it has already demonstrated a non interaction with
      the gamma-aminobutyric acid (GABA)ergic system. For this reason, the objective of
      this work was to evaluate the pharmacological interaction between G-B with the 5
      hydroxytryptamine 1A (5HT(1A)) and 5-hydroxytryptamine 2A (5HT(2A)) serotonergic
      receptors on CA1 neurons of hippocampus. MATERIALS AND METHODS:
      Electrophysiological records were performed as the frequency of discharge of in
      vivo CA1 cells from dorsal hippocampus in rats. RESULTS: G-B was able to increase
      the frequency of discharge of neurons of the CA1 cells with some characteristics
      that support an interaction with the serotonergic system in this zone. It was
      demonstrated that this triterpene modulates the induced response of 5HT(1A)
      receptors, in an allosteric manner. CONCLUSION: This effect demonstrated an
      interaction between G-B and the serotonergic system in dorsal hippocampus and
      evidenced that the mechanism of action of this compound could involve a complex
      series of actions on different neurotransmitter systems related with the anxiety
      disorder.

PMID- 21742024
TI  - Life-extending dietary restriction and ovariectomy result in similar feeding
      rates but different physiologic responses in grasshoppers.
AB  - Dietary restriction (DR) and reduced reproduction each extend life span in many
      species. Females undergoing DR typically experience a reduction in their
      fecundity, which raises the question of whether the two treatments are actually
      extending life span in overlapping ways. Life span in lubber grasshoppers has
      been shown to be increased by DR, and separately by ovariectomy (OVX). Here, we
      test the combination of these on life span. If life extension by the two
      treatments are additive, it would suggest that they likely act through separate
      pathways. The experimental groups were: fully reproductive and fully fed
      (ShamFD); ovariectomized and fully fed (OVXFD); fully reproductive and restricted
      diet (ShamDR); and ovariectomized and restricted diet (OVXDR). The median life
      spans of these groups were: ShamFD=245 d, OVXFD=285 d, ShamDR=286 d, and
      OVXDR=322 d. Feeding rate for the OVXFD group was 64% of ad libitum, similar to
      the 70% of ad libitum that was used for ShamDR. We also measured hemolymph
      parameters of physiology in these same individuals. Hemolymph levels of
      vitellogenin (the egg yolk-precursor protein) were increased 5-fold by OVX, but
      were not affected by DR. In addition, hemolymph total anti-oxidant activity (per
      MUg protein) was significantly reduced by OVX, but was not affected by DR. We
      show that OVX and DR produce different physiological responses in grasshoppers,
      despite life extensions and feeding levels that were not significantly different.
      These data suggest that OVX and DR might extend life span via distinct pathways.

PMID- 21742025
TI  - Sponge-associated microbial Antarctic communities exhibiting antimicrobial
      activity against Burkholderia cepacia complex bacteria.
AB  - The aerobic heterotrophic bacterial communities isolated from three different
      Antarctic sponge species were analyzed for their ability to produce antimicrobial
      compounds active toward Cystic Fibrosis opportunistic pathogens belonging to the
      Burkholderia cepacia complex (Bcc). The phylogenetic analysis performed on the
      16S rRNA genes affiliated the 140 bacterial strains analyzed to 15 genera. Just
      three of them (Psychrobacter, Pseudoalteromonas and Arthrobacter) were shared by
      the three sponges. The further Random Amplified Polymorphic DNA analysis allowed
      to demonstrate that microbial communities are highly sponge-specific and a very
      low degree of genus/species/strain sharing was detected. Data obtained revealed
      that most of these sponge-associated Antarctic bacteria and belonging to
      different genera were able to completely inhibit the growth of bacteria belonging
      to the Bcc. On the other hand, the same Antarctic strains did not have any effect
      on the growth of other pathogenic bacteria, strongly suggesting that the
      inhibition is specific for Bcc bacteria. Moreover, the antimicrobial compounds
      synthesized by the most active Antarctic bacteria are very likely Volatile
      Organic Compounds (VOCs), a finding that was confirmed by the SPME-GC-MS
      technique, which revealed the production of a large set of VOCs by a
      representative set of Antarctic bacteria. The synthesis of these VOCs appeared to
      be related neither to the presence of pks genes nor the presence of plasmid
      molecules. The whole body of data obtained in this work indicates that sponge
      associated bacteria represent an untapped source for the identification of new
      antimicrobial compounds and are paving the way for the discovery of new drugs
      that can be efficiently and successfully used for the treatment of CF infections.

PMID- 21742026
TI  - Candida albicans enhances invasion of human gingival epithelial cells and
      gingival fibroblasts by Porphyromonas gingivalis.
AB  - Although Candida albicans has been isolated from periodontal pockets, its
      relationship to periodontitis is unclear. In this study, we investigated the
      effect of C. albicans on the adhesion and invasion of Ca9-22, a human gingival
      epithelial cell line, and human gingival fibroblasts by Porphyromonas gingivalis.
      Heat-killed C. albicans and water-soluble mannoprotein-beta-glucan complex from
      C. albicans (CAWS) did not enhance P. gingivalis adhesion or upregulate the
      expression of beta1 integrin and ICAM-1, which are required for P. gingivalis
      invasion; both the epithelial cells and fibroblasts expressed dectin-1, which
      recognizes components of the C. albicans cell wall. However, pretreatment of Ca9
      22 cells and human gingival fibroblasts with heat-killed C. albicans or CAWS
      significantly enhanced P. gingivalis invasion. These results suggest that C.
      albicans may exacerbate infectious disease by enhancing the invasion of host
      cells by anaerobic bacteria.

PMID- 21742027
TI  - Identification and analysis of potential virulence-associated genes in
      Haemophilus parasuis based on genomic subtraction.
AB  - Haemophilus parasuis is a commensal bacterium in the swine upper respiratory
      tract, but virulent strains can invade host and cause Glasser's disease under
      certain conditions. In order to explore the virulence difference in H. parasuis
      strains, a virulent isolate, SH0165 (serotype 5), and an avirulent isolate, 7140
      (serotype 4), were selected to investigate genetic differences by genomic
      subtraction. A total of 560 clones were screened by dot-blot and PCR, and 33
      fragments present in SH0165 but absent from 7140 were identified. They encode
      eight gene categories, the sclB family, restriction modification system, phage
      products, transport system, outer membrane proteins, metabolism, and DNA
      synthesis and insertion sequences. We investigated the distribution of 21
      fragments in 15 reference strains. Six fragments were more prevalent in virulent
      strains than avirulent strains based on statistical analysis; three fragments
      were SH0165-specific, and the remaining 12 were diversely distributed. Having
      analyzed these significantly differential fragments, including the sclB family,
      ABC-type transporter, fhuA and nhaC, we presume that these genes are associated
      with virulence in H. parasuis.

PMID- 21742029
TI  - The Pseudomonas aeruginosa quinolone quorum sensing signal alters the
      multicellular behaviour of Pseudomonas putida KT2440.
AB  - The molecule 2-heptyl-3-hydroxy-4-quinolone (referred to as the Pseudomonas
      quinolone signal, or PQS) is produced by Pseudomonas aeruginosa as part of its
      quorum sensing circuit, and has been shown to influence a variety of processes in
      this bacterium, including the production of siderophores and secondary
      metabolites, virulence determinants and biofilm development. In this report we
      present evidence of the effect of PQS as an interspecies signal with a negative
      impact on the multicellular behaviour of Pseudomonas putida KT2440. PQS reduces
      biofilm formation and swarming motility, and interferes with iron uptake by this
      bacterium. Addition of PQS also causes changes in the transcription of several P.
      putida genes, indicating a specific response to the signal molecule, which is not
      produced by strain KT2440. Among the genes with increased expression in response
      to PQS is PP1563, which forms part of a large prophage cluster (PP1532-PP1584);
      consistently, phage-mediated lysis of some cells in the population was observed
      in the presence of PQS. Overall, these data indicate that PQS may be used by P.
      aeruginosa as a chemical weapon against potential competitors.

PMID- 21742028
TI  - Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide
      production.
AB  - Endothelial dysfunction is associated with increase in oxidative stress and low
      NO bioavailability. The endothelial NO synthase (eNOS) uncoupling is considered
      an important factor in endothelial cell oxidative stress. Under increased
      oxidative stress, the eNOS cofactor tetrahydrobiopterin (BH(4)) is oxidized to
      dihydrobiopterin, which competes with BH(4) for binding to eNOS, resulting in
      eNOS uncoupling and reduction in NO production. The importance of the ratio of
      BH(4) to oxidized biopterins versus absolute levels of total biopterin in
      determining the extent of eNOS uncoupling remains to be determined. We have
      developed a computational model to simulate the kinetics of the biochemical
      pathways of eNOS for both NO and O(2)(*-) production to understand the roles of
      BH(4) availability and total biopterin (TBP) concentration in eNOS uncoupling.
      The downstream reactions of NO, O(2)(*-), ONOO(-), O(2), CO(2), and BH(4) were
      also modeled. The model predicted that a lower [BH(4)]/[TBP] ratio decreased NO
      production but increased O(2)(*-) production from eNOS. The NO and O(2)(*-)
      production rates were independent above 1.5MUM [TBP]. The results indicate that
      eNOS uncoupling is a result of a decrease in [BH(4)]/[TBP] ratio, and a
      supplementation of BH(4) might be effective only when the [BH(4)]/[TBP] ratio
      increases. The results from this study will help us understand the mechanism of
      endothelial dysfunction.

PMID- 21742030
TI  - Preparation of an anhydrous reverse micelle delivery system to enhance oral
      bioavailability and anti-diabetic efficacy of berberine.
AB  - To enhance oral bioavailability and anti-diabetic efficacy of berberine (BER), an
      anhydrous reverse micelle (ARM) delivery system was prepared through
      lyophilization of water-in-oil (W/O) emulsions. Using soy phosphatidylcholine as
      emulsifiers, BER-containing W/O emulsions were prepared and then lyophilized to
      form dry products which, upon addition of oil, formed clear ARMs containing
      amorphous BER nanoparticles. BER-loaded ARMs or free BER solutions were
      administered to streptozocin-induced diabetic mice. In vivo measurements
      demonstrated that the blood glucose levels (BGLs) of diabetic mice reduced on
      average to 22% of the initial values 4h after intravenous injection of BER
      solution at the dose of 2.5mg/kg body weight, while the average BGL reduction was
      57% in the group gavaged with ARMs at the dose of 100mg/kg body weight. No
      significant BGL reduction was noticed in mice orally received BER solutions.
      Compared to BER solutions, the oral bioavailability of BER-loaded ARMs was
      enhanced 2.4-fold, and the maximum blood concentration of BER was enhanced 2.1
      fold with a 2-h time lag leading to a prolonged efficacy. Thus, this novel ARM
      delivery system provides a valid method to improve oral bioavailability and anti
      diabetic efficacy of BER, offering a promising product alternative to other
      hypoglycemic drugs for diabetes therapy.

PMID- 21742031
TI  - Characterization of an allatotropin-like peptide receptor in the red flour
      beetle, Tribolium castaneum.
AB  - Following a reverse pharmacology approach, we identified an allatotropin-like
      peptide receptor in Tribolium castaneum. Allatotropins are multifunctional
      neuropeptides initially isolated from the tabacco hornworm, Manduca sexta. They
      have been shown to be myoactive, to be cardio-acceleratory, to inhibit active ion
      transport, to stimulate juvenile hormone production and release and to be
      involved in the photic entrainment of the circadian clock. A tissue distribution
      analysis of the T. castaneum allatotropin-like peptide receptor by means of qRT
      PCR revealed a prominent sexual dimorphism, the transcript levels being
      significantly higher in the male fat body and reproductive system. The endogenous
      ligand of the receptor, Trica-ATL, is able to increase the frequency and tonus of
      contractions in the gut and in the reproductive tract of mature red flour
      beetles.

PMID- 21742032
TI  - Influence of immunosuppressive agents on tryptophan degradation and neopterin
      production in human peripheral blood mononuclear cells.
AB  - The anti-proliferative and immunomodulatory enzyme indoleamine 2,3-dioxygenase
      (IDO) degrades the essential amino acid tryptophan via the kynurenine pathway.
      IDO is stimulated during cellular immune responses preferentially by Th1-type
      cytokine interferon-gamma (IFN-gamma). IDO activity is estimated by calculating
      the kynurenine to tryptophan ratio (Kyn/Trp). In human monocyte-derived
      macrophages and dendritic cells, GTP-cyclohydrolase I is induced in parallel to
      IDO and produces neopterin. This study investigated the effects of common
      immunosuppressants on freshly isolated human peripheral blood mononuclear cells
      (PBMC) in vitro. PBMC were incubated with compounds for 30 min and then either
      left unstimulated or stimulated with mitogen phytohaemagglutinin (PHA).
      Concentrations of tryptophan, kynurenine and neopterin were measured in
      supernatants after 48 h. Kyn/Trp, neopterin and IFN-gamma concentrations were
      significantly higher in PHA-stimulated vs. unstimulated PBMC. Tacrolimus (FK506),
      cyclosporine A (CsA), sirolimus and methylprednisolone dose-dependently inhibited
      tryptophan degradation and neopterin production. FK506, CsA and sirolimus showed
      significant inhibition at concentrations as low as 0.1 MUg/ml, whereas
      prednisolone and methylprednisolone required higher doses to suppress tryptophan
      degradation. Mycophenolate-mofetil suppressed neopterin formation more
      efficiently than Kyn/Trp. All tested drugs also strongly decreased mitogen
      induced IFN-gamma concentrations. Overall the investigated immunosuppressants are
      effective to inhibit IDO activity and neopterin production in a similar and dose
      dependent manner, however with some differences in IC50s when comparing
      individual compounds. The corresponding changes of IFN-gamma concentrations are
      in line with its role as a trigger of both biochemical changes.

PMID- 21742033
TI  - Rotenone induces degeneration of photoreceptors and impairs the dopaminergic
      system in the rat retina.
AB  - Rotenone is a widely used pesticide and a potent inhibitor of mitochondrial
      complex I (NADH-quinone reductase) that elicits the degeneration of dopaminergic
      neurons and thereby the appearance of a parkinsonian syndrome. Here we have
      addressed the alterations induced by rotenone at the functional, morphological
      and molecular levels in the retina, including those involving both dopaminergic
      and non-dopaminergic retinal neurons. Rotenone-treated rats showed abnormalities
      in equilibrium, postural instability and involuntary movements. In their outer
      retina we observed a loss of photoreceptors, and a reduced synaptic connectivity
      between those remaining and their postsynaptic neurons. A dramatic loss of
      mitochondria was observed in the inner segments, as well as in the axon terminals
      of photoreceptors. In the inner retina we observed a decrease in the expression
      of dopaminergic cell molecular markers, including loss of tyrosine hydroxylase
      immunoreactivity, associated with a reduction of the dopaminergic plexus and cell
      bodies. An increase in immunoreactivity of AII amacrine cells for parvalbumin, a
      Ca(2+)-scavenging protein, was also detected. These abnormalities were
      accompanied by a decrease in the amplitude of scotopic and photopic a- and b
      waves and an increase in the b-wave implicit time, as well as by a lower
      amplitude and greater latency in oscillatory potentials. These results indicate
      that rotenone induces loss of vision by promoting photoreceptor cell death and
      impairment of the dopaminergic retinal system.

PMID- 21742034
TI  - Differential impact of diabetes and hypertension in the brain: adverse effects in
      grey matter.
AB  - Diabetes mellitus types 1 and 2 (DM1 and DM2) and/or hypertension (HTN) can
      contribute to cognitive decline, cerebral atrophy and white matter abnormalities
      in humans. Adult rat models of streptozotocin-induced DM1 and genetic strains of
      DM2 and HTN were used to investigate relative contributions of DM and HTN for
      alterations in cerebral structure and function as well as insulin receptor
      biology using cognitive testing, magnetic resonance imaging (MRI), and
      histological and molecular methods. The effects of DM1 or DM2 were generally
      similar. DM was associated with earlier onset of cognitive impairment than with
      HTN alone. DM was independently correlated with brain atrophy, whereas HTN had
      minimal effects on brain volume. The combination of DM and HTN led to
      identifiable mild hippocampal neuronal loss while either DM or HTN led to
      synaptic loss. Only DM led to downregulation of the insulin receptor pathways'
      activation. In contrast, only HTN was associated with vascular luminal reduction
      and restricted cerebral perfusion on MRI. The impacts of DM and HTN in the brain
      differ, while their separate contributions can lead to some additive adverse
      effects within rodent brain grey matter.

PMID- 21742035
TI  - Abnormal prostaglandin E2 production blocks myogenic differentiation in myotonic
      dystrophy.
AB  - The congenital form of myotonic dystrophy type 1 (DM1) is the most severe type of
      the disease associated with CTG expansions over 1500 repeats and delayed muscle
      maturation. The mechanistic basis of the congenital form of DM1 is mostly
      unknown. Here, we show that muscle satellite cells bearing large CTG expansions
      (>3000) secrete a soluble factor that inhibits the fusion of normal myoblasts in
      culture. We identified this factor as prostaglandin E2 (PGE(2)). In these DM1
      cells, PGE(2) production is increased through up-regulation of cyclooxygenase 2
      (Cox-2), mPGES-1 and prostaglandin EP2/EP4 receptors. Elevated levels of PGE(2)
      inhibit myogenic differentiation by decreasing the intracellular levels of
      calcium. Exogenous addition of acetylsalicylic acid, an inhibitor of Cox enzymes,
      abolishes PGE(2) abnormal secretion and restores the differentiation of DM1
      muscle cells. These data indicate that the delay in muscle maturation observed in
      congenital DM1 may result, at least in part, from an altered autocrine mechanism.
      Inhibitors of prostaglandin synthesis may thus offer a powerful method to restore
      the differentiation of DM1 muscle cells.

PMID- 21742036
TI  - Lafora disease ubiquitin ligase malin promotes proteasomal degradation of
      neuronatin and regulates glycogen synthesis.
AB  - Lafora disease (LD) is the inherited progressive myoclonus epilepsy caused by
      mutations in either EPM2A gene, encoding the protein phosphatase laforin or the
      NHLRC1 gene, encoding the ubiquitin ligase malin. Since malin is an ubiquitin
      ligase and its mutations cause LD, it is hypothesized that improper clearance of
      its substrates might lead to LD pathogenesis. Here, we demonstrate for the first
      time that neuronatin is a novel substrate of malin. Malin interacts with
      neuronatin and enhances its degradation through proteasome. Interestingly,
      neuronatin is an aggregate prone protein, forms aggresome upon inhibition of
      cellular proteasome function and malin recruited to those aggresomes. Neuronatin
      is found to stimulate the glycogen synthesis through the activation of glycogen
      synthase and malin prevents neuronatin-induced glycogen synthesis. Several LD
      associated mutants of malin are ineffective in the degradation of neuronatin and
      suppression of neuronatin-induced glycogen synthesis. Finally, we demonstrate the
      increased levels of neuronatin in the skin biopsy sample of LD patients. Overall,
      our results indicate that malin negatively regulates neuronatin and its loss of
      function in LD results in increased accumulation of neuronatin, which might be
      implicated in the formation of Lafora body or other aspect of disease
      pathogenesis.

PMID- 21742037
TI  - Cytochrome P450 is regulated by noradrenergic and serotonergic systems.
AB  - The aim of the present study was to ascertain whether the noradrenergic or
      serotonergic systems may affect the expression of liver cytochrome P450 (CYP).
      Rats were injected intraperitoneally with N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4, a noradrenergic neurotoxin) or p-chloroamphetamine (PCA,
      a serotonergic neurotoxin) or p-chlorophenylalanine (PCPA, an inhibitor of
      serotonin synthesis). One week after neurotoxin injection the levels of
      neurotransmitters (noradrenaline, dopamine, serotonin) and their metabolites were
      measured in brain structures, and the activity and protein levels of CYP isoforms
      were measured in the liver. In the brain, DSP-4 or PCA and PCPA selectively
      decreased noradrenaline or serotonin levels, respectively. In the liver, the
      applied neurotoxins evoked decrease in the activity of CYP2B, CYP2C11 and CYP3A
      (DSP-4, PCA, PCPA) and increase in the activity of CYP1A (PCA, PCPA), while the
      activity of CYP2A, CYP2C6 and CYP2D was not affected by the applied neurotoxins.
      Since the affected isoforms (CYP1A/2B/2C11/3A) are regulated by endogenous
      hormones (growth hormone, corticosterone, thyroid hormones), the latter being
      under control of the central nervous system, it is postulated that the brain
      noradrenergic and serotonergic systems are involved in the physiological
      regulation of liver CYP expression.

PMID- 21742038
TI  - Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are
      associated with fatal outcome in a multicentre, prospective cohort study.
      Hypothetical impact of tetracyclines.
AB  - Recent evidence suggests that matrix metalloproteinases (MMPs) and their
      endogenous inhibitors are involved in the pathogenesis of sepsis. We studied
      serum levels of MMP-8, MMP-9 and TIMP-1 (tissue inhibitor of matrix
      metalloproteinase-1) in a multicentre, prospective cohort study of patients with
      sepsis treated in Intensive Care Units (ICUs). We analyzed serum samples taken on
      ICU admission from 248 critically ill sepsis patients. MMP-8, -9 and TIMP-1 serum
      levels were analyzed by enzyme-linked immunosorbent assays. Serum MMP-8, MMP-9
      and TIMP-1 levels were significantly higher in patients with severe sepsis than
      in healthy controls. Serum MMP-8 levels among non-survivors (n=33) were
      significantly (p=0.006) higher than among survivors (n=215). Serum TIMP-1 but not
      MMP-9 levels were significantly higher among non-survivors than survivors
      (p<0.0001, p=0.079, respectively). Systemic MMP-8 is upregulated in sepsis
      suggesting that MMP-8 may contribute to the host response during sepsis. High
      serum MMP-8 and TIMP-1 levels at ICU admission were seen among patients with
      fatal outcome. With this background, clinical studies examining the ability of
      MMP-inhibitors (such as the non-antimicrobial properties of tetracyclines) to
      diminish the MMP-mediated inflammatory response are needed to develop novel
      therapies in order to improve the outcome of sepsis.

PMID- 21742039
TI  - Polyphenol rich botanicals used as food supplements interfere with EphA2-ephrinA1
      system.
AB  - The Eph tyrosine kinase receptors and their ephrin ligands play a central role in
      several human cancers and their deregulated expression or function promotes
      tumorigenesis, inducing aggressive tumor phenotypes. Green tea extracts (GTE)
      have been recently found to inhibit Eph-kinase phosphorylation. In order to
      evaluate the potential contribution of edible and medicinal plants on EphA2
      ephrinA1 modulation, 133 commercially available plant extracts used as food
      supplements, essential and fixed oils were screened with an ELISA-based binding
      assay. Nine plant extracts, rich of polyphenols, reversibly inhibited binding in
      a dose-dependent manner (IC50 0.83-24 MUg/ml). Functional studies on PC3 prostate
      adenocarcinoma cells revealed that active extracts antagonized ephrinA1-Fc
      induced EphA2-phosphorylation at non-cytotoxic concentrations (IC50 0.31-11.3
      MUg/ml) without interfering with EGF-induced EGFR activation, suggesting a
      specific effect. These findings could furnish an interesting starting point
      regarding the potential relationship between diet, edible plant secondary
      metabolites and Eph-ephrin system, suggesting their possible involvement in
      cancer development modulation.

PMID- 21742040
TI  - Expression and structural characterization of human translocase of inner membrane
      of mitochondria Tim50.
AB  - The preprotein translocase of the inner membrane of mitochondria (TIM23 complex)
      is the main entry gate for proteins of the matrix and the inner membrane. Tim50
      is a major receptor in TIM23 complex, which spans the inner membrane with a
      single transmembrane segment and exposes a large hydrophilic domain in the
      intermembrane space. In this study, we expressed and purified the intermembrane
      space (IMS) domain of human Tim50 (Tim50(IMS)), and investigated its structural
      characteristics and assembly behaviors. The far-UV CD spectra of Tim50(IMS) in
      native and denatured states revealed that the protein has a significantly folded
      secondary structure consisted of alpha-helixes and beta-sheets. Size exclusion
      chromatography showed that Tim50(IMS) is a monomer. Furthermore, the results
      showed, by intrinsic fluorescence, ANS binding, fluorescence anisotropy and
      fluorescence quenching, that Tim50(IMS) forms a compact structure in the range of
      pH 8.0-5.0; and it is more compact at pH 8.0 than pH 7.0; when pH decreases below
      5.0, the protein is gradually denatured.

PMID- 21742041
TI  - The face is more than its parts--brain dynamics of enhanced spatial attention to
      schematic threat.
AB  - A rapid response to environmental threat is crucial for survival and requires an
      appropriate attention allocation toward its location. Visual search paradigms
      have provided evidence for the enhanced capture of attention by threatening
      faces. In two EEG experiments, we sought to determine whether the detection of
      threat requires complete faces or salient features underlying the facial
      expression. Measuring the N2pc component as an electrophysiological indicator of
      attentional selection we investigated participants searching for either a
      complete discrepant schematic threatening or friendly face within an array of
      neutral faces, or single features (eyebrows and eyes vs. eyebrows) of threatening
      and friendly faces. Threatening faces were detected faster compared to friendly
      faces. In accordance, threatening angry targets showed a more pronounced
      occipital N2pc between 200 and 300 ms than friendly facial targets. Moreover,
      threatening configurations, were detected more rapidly than friendly-related
      features when the facial configuration contained eyebrows and eyes. No
      differences were observed when only a single feature (eyebrows) had to be
      detected. Threatening-related and friendly-related features did not show any
      differences in the N2pc across all configuration conditions. Taken together, the
      findings provide direct electrophysiological support for rapid prioritized
      attention to facial threat, an advantage that seems not to be driven by low level
      visual features.

PMID- 21742042
TI  - Motor and attentional mechanisms involved in social interaction--evidence from mu
      and alpha EEG suppression.
AB  - Mu rhythms are EEG oscillations in the 8-13 Hz recorded at sites located roughly
      over the sensory-motor cortex. There is reliable evidence that the amplitude of
      mu rhythms is reduced when the participant performs a motor act (mu suppression).
      Recent studies found mu suppression not only in response to actual movements but
      also while the participant observes actions executed by someone else. This
      finding putatively associates the mu suppression to the activity of a mirror
      neurons system which, in humans, has been suggested to contribute to social
      skills. In the present study we explored the effects of different levels of
      social interaction on mu suppression. Participants observed dynamic displays of
      hand gestures performing actions used in the Rock-Scissors-Paper game. In
      different blocks, participants passively viewed identical video clips with no
      game context and in the context of a game, or while being actually engaged in the
      game either by imagining actions or by actual playing. As a baseline for
      calculating mu suppression we used a dynamic display of a rolling ball. In
      addition, to isolate the social aspect of the actual movements, participants
      performed the same acts outside the game context. Mu suppression was larger while
      participants were engaged in the social game than when they passively looked at
      the "opponent" actions or when they performed movements without the game context.
      This effect was found while viewing the opponent play as well as while actually
      playing, which supports the view that mu suppression is affected not only by
      motion, but also by the social context of the motion. However, we did not find
      differences in mu suppression between perception segments in which the
      participant did not actually play. Furthermore, in all perception segments
      occipital alpha suppression was more robust than mu suppression suggesting the
      involvement of a strong attentional component. While actually playing, however,
      mu suppression was stronger than alpha suppression.

PMID- 21742043
TI  - Simultaneous acquisition of corrugator electromyography and functional magnetic
      resonance imaging: a new method for objectively measuring affect and neural
      activity concurrently.
AB  - The development of functional neuroimaging of emotion holds the promise to
      enhance our understanding of the biological bases of affect and improve our
      knowledge of psychiatric diseases. However, up to this point, researchers have
      been unable to objectively, continuously and unobtrusively measure the intensity
      and dynamics of affect concurrently with functional magnetic resonance imaging
      (fMRI). This has hindered the development and generalizability of our field.
      Facial electromyography (EMG) is an objective, reliable, valid, sensitive, and
      unobtrusive measure of emotion. Here, we report the successful development of a
      method for simultaneously acquiring fMRI and facial EMG. The ability to
      simultaneously acquire brain activity and facial physiology will allow affective
      neuroscientists to address theoretical, psychiatric, and individual difference
      questions in a more rigorous and generalizable way.

PMID- 21742044
TI  - Evaluating phylogenetic informativeness and data-type usage for new protein
      coding genes across Vertebrata.
AB  - As a resource for vertebrate phylogenetics, we developed 75 new protein-coding
      genes using a combination of expressed sequence tags (ESTs) available in Genbank,
      and targeted amplification of complementary DNA (cDNA). In addition, we performed
      three additional analyses in order to assess the utility of our approach. First,
      we profiled the phylogenetic informativeness of these new markers using the
      online program PhyDesign. Next, we compared the utility of four different data
      types used in phylogenetics: nucleotides (NUCL), amino acids (AA), 1st and 2nd
      codon positions only (N12), and modified sequences to account for codon
      degeneracy (DEGEN1; Regier et al., 2010). Lastly, we use these new markers to
      construct a vertebrate phylogeny and address the uncertain relationship between
      higher-level mammal groups: monotremes, marsupials, and placentals. Our results
      show that phylogenetic informativeness of the 75 new markers varies, both in the
      amount of phylogenetic signal and optimal timescale. When comparing the four data
      types, we find that the NUCL data-type, due to the high level of phylogenetic
      signal, performs the best across all divergence times. The remaining three data
      types (AA, N12, DEGEN1) are less subject to homoplasy, but have greatly reduced
      levels of phylogenetic signal relative to NUCL. Our phylogenetic inference
      supports the Theria hypothesis of mammalian relationships, with marsupials and
      placentals being sister groups.

PMID- 21742045
TI  - Elemental and non-elemental olfactory learning in Drosophila.
AB  - Brain complexity varies across many orders of magnitude between animals, and it
      is often assumed that complexity underpins cognition. It is thus important to
      explore the cognitive capacity of widely used model organisms such as Drosophila.
      We systematically investigated the fly's ability to learn discriminations
      involving compound olfactory stimuli associated with shock. Flies could
      distinguish binary mixtures (AB+ CD-), including overlapping mixtures (AB+ BC-).
      They could learn positive patterning (AB+A- B-) but could not learn negative
      patterning (A+ B+ AB-) or solve a biconditional discrimination task (AB+ CD+ AC-
      BD-). Learning about the elements of a compound (AB+) was not affected by prior
      conditioning of one of the elements (A+ AB+): flies do not exhibit blocking in
      this task. We compare these results with the predictions from simulation of
      several well-known theoretical models of learning, and find none are fully
      consistent with the overall pattern of observed behaviour.

PMID- 21742046
TI  - Septal area lesions impair spatial working memory in homing pigeons (Columba
      livia).
AB  - The septo-hippocampal system in birds resembles that of mammals, motivating
      research into the function of the avian hippocampus while surprisingly little
      attention has been given to the septum. To investigate a possible role of the
      avian septum in memory, the effects of septal area lesions on a spatial working
      memory (SpWM) task was tested in homing pigeons. After preoperative training on
      an analogue eight-arm (feeders) radial maze, now sham-operated control and septal
      lesioned pigeons were then trained again on the same task of locating the four
      feeders on the test phase of a trial that were not baited during the sample phase
      of a trial. During the test phase of a working memory trial, septal lesioned
      pigeons, compared to both their own preoperative performance and the performance
      of the controls, required significantly more choices to locate the four baited
      feeders not baited during the sample phase of a trial, and they made
      significantly fewer correct responses to the now baited feeders on their first
      four choices. The results demonstrate that, like its mammalian counterpart, the
      avian septum plays an important role in SpWM, suggesting that at least some
      functional properties of the septum are evolutionarily conserved in birds and
      mammals.

PMID- 21742047
TI  - The role of the dorsal and ventral hippocampus in olfactory working memory.
AB  - Olfactory working memory and pattern separation for odor information was assessed
      in male rats using a matching-to-sample for odors paradigm. The odor set
      consisted of a five aliphatic acids with unbranched carbon chains that varied
      from two- to six-carbons in length. Each trial consisted of a sample phase
      followed by a choice phase. During the sample phase, rats would receive one of
      five different odors. Fifteen seconds later during the choice phase one of the
      previous odors was presented simultaneously side by side with a different odor
      that was based on the number of aliphatic acids that varied in the carbon chains
      from two- to six-carbons in length and rats were allowed to choose between the
      two odors. The rule to be learned in order to receive a food reward was to always
      choose the odor that occurred during the study phase. Odor separations of 1, 2, 3
      or 4 were selected for each choice phase and represented the carbon chain
      difference between the study phase odor and the test phase odor. Once an animal
      reached a criterion of 80-90% correct across all temporal separations based on 40
      trials, rats received a control, dorsal hippocampal, or ventral hippocampal
      lesion and were retested on the task. On postoperative trials, only the ventral
      hippocampal lesion group was impaired relative to both control and dorsal
      hippocampal groups groups. There were no effects on odor pattern separation. All
      groups of rats could discriminate between the odors. The data suggest that the
      ventral hippocampus, but not dorsal hippocampus, supports working memory for odor
      information.

PMID- 21742048
TI  - Nitric oxide promotes nicotine-triggered ERK signaling via redox reactions in
      PC12 cells.
AB  - Nitric oxide (NO), produced by neuronal NO synthase (nNOS), serves as a signaling
      molecule with diverse biological responses in the central nervous system (CNS).
      In the present study, we demonstrated that nNOS expression enhances the nicotine
      triggered activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in
      nNOS-transfected PC12 (NPC12) cells. Treatment with nicotine increased the
      phosphorylation level of ERK1/2 in the NPC12 cells as compared with that in
      control PC12 cells. However, nicotine treatment failed to enhance ERK1/2
      phosphorylation when NPC12 cells were pretreated with several selective
      inhibitors of NOS, the nicotinic acetylcholine receptors, L-type voltage
      dependent Ca(2+) channels, protein kinase C, Src, epidermal growth factor
      receptor, and MEK. The nicotine-induced ERK1/2 phosphorylation in PC12 cells was
      observed by their pretreatment with a NO donor. Moreover, the enhancement of
      nicotine-induced ERK1/2 phosphorylation in the NPC12 cells was regulated by
      intracellular glutathione levels, but not by the soluble guanylate cyclase-cGMP
      protein kinase G signaling. Meanwhile, depolarization stimulated ERK1/2
      phosphorylation in both PC12 and NPC12 cells. Taken together, these findings
      suggest that nicotine modulates NO-dependent redox condition; the resulting
      calcium influx, would increase ERK1/2 phosphorylation in nNOS expressing cells.
      Blockade of NO pathway may be selective target to reduce ERK1/2 phosphorylation
      via attenuation of the nicotine responses in the CNS.

PMID- 21742049
TI  - CO2 induced seawater acidification impacts sea urchin larval development II: gene
      expression patterns in pluteus larvae.
AB  - Extensive use of fossil fuels is leading to increasing CO(2) concentrations in
      the atmosphere and causes changes in the carbonate chemistry of the oceans which
      represents a major sink for anthropogenic CO(2). As a result, the oceans' surface
      pH is expected to decrease by ca. 0.4 units by the year 2100, a major change with
      potentially negative consequences for some marine species. Because of their
      carbonate skeleton, sea urchins and their larval stages are regarded as likely to
      be one of the more sensitive taxa. In order to investigate sensitivity of pre
      feeding (2 days post-fertilization) and feeding (4 and 7 days post-fertilization)
      pluteus larvae, we raised Strongylocentrotus purpuratus embryos in control (pH
      8.1 and pCO(2) 41 Pa e.g. 399 MUatm) and CO(2) acidified seawater with pH of 7.7
      (pCO(2) 134 Pa e.g. 1318 MUatm) and investigated growth, calcification and
      survival. At three time points (day 2, day 4 and day 7 post-fertilization), we
      measured the expression of 26 representative genes important for metabolism,
      calcification and ion regulation using RT-qPCR. After one week of development, we
      observed a significant difference in growth. Maximum differences in size were
      detected at day 4 (ca. 10% reduction in body length). A comparison of gene
      expression patterns using PCA and ANOSIM clearly distinguished between the
      different age groups (two-way ANOSIM: Global R=1) while acidification effects
      were less pronounced (Global R=0.518). Significant differences in gene expression
      patterns (ANOSIM R=0.938, SIMPER: 4.3% difference) were also detected at day 4
      leading to the hypothesis that differences between CO(2) treatments could reflect
      patterns of expression seen in control experiments of a younger larva and thus a
      developmental artifact rather than a direct CO(2) effect. We found an up
      regulation of metabolic genes (between 10%and 20% in ATP-synthase, citrate
      synthase, pyruvate kinase and thiolase at day 4) and down regulation of
      calcification related genes (between 23% and 36% in msp130, SM30B, and SM50 at
      day 4). Ion regulation was mainly impacted by up regulation of Na(+)/K(+)-ATPase
      at day 4 (15%) and down regulation of NHE3 at day 4 (45%). We conclude that in
      studies in which a stressor induces an alteration in the speed of development, it
      is crucial to employ experimental designs with a high time resolution in order to
      correct for developmental artifacts. This helps prevent misinterpretation of
      stressor effects on organism physiology.

PMID- 21742050
TI  - CO2 induced seawater acidification impacts sea urchin larval development I:
      elevated metabolic rates decrease scope for growth and induce developmental
      delay.
AB  - Anthropogenic CO(2) emissions are acidifying the world's oceans. A growing body
      of evidence is showing that ocean acidification impacts growth and developmental
      rates of marine invertebrates. Here we test the impact of elevated seawater
      pCO(2) (129 Pa, 1271 MUatm) on early development, larval metabolic and feeding
      rates in a marine model organism, the sea urchin Strongylocentrotus purpuratus.
      Growth and development was assessed by measuring total body length, body rod
      length, postoral rod length and posterolateral rod length. Comparing these
      parameters between treatments suggests that larvae suffer from a developmental
      delay (by ca. 8%) rather than from the previously postulated reductions in size
      at comparable developmental stages. Further, we found maximum increases in
      respiration rates of +100% under elevated pCO(2), while body length corrected
      feeding rates did not differ between larvae from both treatments. Calculating
      scope for growth illustrates that larvae raised under high pCO(2) spent an
      average of 39 to 45% of the available energy for somatic growth, while control
      larvae could allocate between 78 and 80% of the available energy into growth
      processes. Our results highlight the importance of defining a standard frame of
      reference when comparing a given parameter between treatments, as observed
      differences can be easily due to comparison of different larval ages with their
      specific set of biological characters.

PMID- 21742051
TI  - Responses of free radical metabolism to air exposure or salinity stress, in crabs
      (Callinectes danae and C. ornatus) with different estuarine distributions.
AB  - The swimming crabs Callinectes danae and C. ornatus are found in bays and
      estuaries, but C. danae is more abundant in lower salinities, while C. ornatus
      remains restricted to areas of higher salinity. Experimental crabs of both
      species were submitted to: air exposure (Ae, 3h), reimmersion in 330/00 (control)
      sea water (SW) (Ri, 1h) following air exposure; hyposaline (Ho, 100/00 for 2h) or
      hypersaline (He, 400/00 for 2h) SW, then return to control 330/00 SW (RHo and
      RHe, for 1h). Hemolymph was sampled for osmolality and chloride determinations.
      Activity of antioxidant enzymes [glutathione peroxidase (GPX), catalase,
      glutathione-S-transferase] and levels of carbonyl proteins and lipid peroxidation
      (TBARS) were evaluated in hepatopancreas, muscle, anterior and posterior gills.
      In Ho groups, hemolymph concentrations were lower in both species, compared to He
      groups. C. danae displayed higher control activities of GPX (hepatopancreas and
      muscle) and catalase (all four tissues) than C. ornatus. C. ornatus presented
      increased activities of catalase and GPX in Ae, Ri, and He groups. Increased
      TBARS was seen in C. ornatus tissues (He group). The more euryhaline species
      displayed higher constitutive activities of antioxidant enzymes, and the less
      euryhaline species exhibited activation of these enzymes when exposed to air or
      hyper-salinity.

PMID- 21742052
TI  - Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin
      induced diabetic mice.
AB  - Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into
      epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the
      cardiovascular system. The anti-inflammatory, anti-apoptotic, pro-angiogenic, and
      anti-hypertensive properties of EETs in the cardiovascular system suggest a
      beneficial role for EETs in diabetic nephropathy. This study investigated the
      effects of endothelial specific overexpression of CYP2J2 epoxygenase on diabetic
      nephropathy in streptozotocin-induced diabetic mice. Endothelial CYP2J2
      overexpression attenuated renal damage as measured by urinary microalbumin and
      glomerulosclerosis. These effects were associated with inhibition of TGF
      beta/Smad signaling in the kidney. Indeed, overexpression of CYP2J2 prevented TGF
      beta1-induced renal tubular epithelial-mesenchymal transition in vitro. These
      findings highlight the beneficial roles of the CYP epoxygenase-EET system in the
      pathogenesis of diabetic nephropathy.

PMID- 21742053
TI  - The rod photoreceptor lineage of teleost fish.
AB  - The retinas of postembryonic teleost fish continue to grow for the lifetime of
      the fish. New retinal cells are added continuously at the retinal margin, by stem
      cells residing at the circumferential germinal zone. Some of these retinal cells
      differentiate as Muller glia with cell bodies that reside within the inner
      nuclear layer. These glia retain some stem cell properties in that they carry out
      asymmetric cell divisions and continuously generate a population of transit
      amplifying cells--the rod photoreceptor lineage--that are committed to rod
      photoreceptor neurogenesis. These rod progenitors progress through a stereotyped
      sequence of changes in gene expression as they continue to divide and migrate to
      the outer nuclear layer. Now referred to as rod precursors, they undergo terminal
      mitoses and then differentiate as rods, which are inserted into the existing
      array of rod and cone photoreceptors. The rod lineage displays developmental
      plasticity, as rod precursors can respond to the loss of rods through increased
      proliferation, resulting in rod replacement. The stem cells of the rod lineage,
      Muller glia, respond to acute damage of other retinal cell types by increasing
      their rate of proliferation. In addition, the Muller glia in an acutely damaged
      retina dedifferentiate and become multipotent, generating new, functional
      neurons. This review focuses on the cells of the rod lineage and includes
      discussions of experiments over the last 30 years that led to their
      identification and characterization, and the discovery of the stem cells residing
      at the apex of the lineage. The plasticity of cells of the rod lineage, their
      relationships to cone progenitors, and the applications of this information for
      developing future treatments for human retinal disorders will also be discussed.

PMID- 21742054
TI  - A multiplex SNaPshot assay as a rapid method for detecting KRAS and BRAF
      mutations in advanced colorectal cancers.
AB  - The analysis of KRAS mutations has become a prerequisite for anti-epidermal
      growth factor receptor therapy in patients with metastatic colorectal cancers.
      KRAS mutations are associated with resistance to treatment by monoclonal
      antibodies such as cetuximab and panitumumab and thus are correlated with a
      shorter progression-free survival. BRAF mutations also may play a role in
      treatment decisions. The widespread use of these targeted therapies has generated
      the need to develop cost-effective methods for routine KRAS and BRAF analysis.
      The aim of this study was to compare a multiplex SNaPshot assay with DNA
      sequencing and high-resolution melting analysis for identifying KRAS codons 12
      and 13 and BRAF codon 600 mutations. Thus 110 routinely formalin-fixed and
      paraffin-embedded tissue blocks were tested by each method. The SNaPshot analysis
      detected KRAS and BRAF codon 600 mutations in, respectively, 34.5% (n = 38) and
      10% (n = 11) of these tissue blocks. These results were confirmed by direct DNA
      sequencing and by high-resolution melting analysis. The costs and time
      constraints of each detection method were compared at the same time. In
      conclusion, our newly designed multiplex SNaPshot assay is a fast, inexpensive,
      sensitive, and robust technique for molecular diagnostic practices and patient
      selection.

PMID- 21742055
TI  - Lipid peroxidation and oxidative stress responses of salmon fed a diet containing
      perfluorooctane sulfonic- or perfluorooctane carboxylic acids.
AB  - The present study was conducted to evaluate the effects of perfluorooctane
      sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on lipid beta-oxidation and
      oxidative stress responses in Atlantic salmon liver and kidney tissues. We
      quantified changes in the expression levels of peroxisome proliferator-activated
      receptors (PPARs) and acyl-CoA oxidase (ACOX1) enzyme whose transcription is
      induced by PPARs. In addition, we analyzed gene expression patterns for enzymatic
      antioxidants (superoxide dismutase: SOD, catalase: CAT and glutathione
      peroxidase: GPx). Thiobarbituric acid reactive substances (TBARS) were analyzed
      as a measure for lipid peroxidation. Juvenile Atlantic salmon were repeatedly
      force-fed food spiked with PFOA or PFOS at 0.2mg/kg, and samples were collected
      after 0, 2, 5 and 8 days and after a 7 days recovery period. Our data showed that
      exposure of salmon to PFOS or PFOA produced changes (either increased or
      decreased) in mRNA expression for PPARs, ACOX1, oxidative stress responses and
      lipid peroxidation (TBARS) and these responses showed marked organ differences,
      associated with tissue bioaccumulation patterns and dependent on exposure time.
      Given that a classical reaction during reactive oxygen species (ROS)-induced
      damage involves the peroxidation of lipids, our study demonstrates that salmon
      continuously exposed to dietary PFOS or PFOA dose showed alteration in
      peroxisomal responses and oxidative stress responses, with higher severity in the
      kidney, compared to liver. Overall, our data suggest that ROS-mediated oxidative
      damage maybe a significant and putative toxic effect of PFOA and PFOS in fish as
      has been reported in mammals.

PMID- 21742056
TI  - The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of
      cardiovascular function.
AB  - Endogenous estrogens are important regulators of cardiovascular homeostasis in
      premenopausal women and delay the development of hypertension and coronary artery
      disease. These hormones act via three different estrogen receptors affecting both
      gene transcription and rapid signaling pathways in a complex interplay. In
      addition to the classical estrogen receptors ERalpha and ERbeta, which are known
      mediators of estrogen-dependent vascular effects, a G protein-coupled estrogen
      receptor termed GPER that is expressed in the cardiovascular system has recently
      been identified. Endogenous human 17beta-estradiol, selective estrogen receptor
      modulators (SERMs) including tamoxifen and raloxifene, and selective estrogen
      receptor downregulators (SERDs) such as ICI 182,780 are all agonists of GPER,
      which has been implicated in the regulation of vasomotor tone and protection from
      myocardial ischemia/reperfusion injury. As a result, understanding the individual
      role of ERalpha, ERbeta, and GPER in cardiovascular function has become
      increasingly complex. With accumulating evidence that GPER is responsible for a
      variety of beneficial cardiovascular effects of estrogens, this receptor may
      represent a novel target to develop effective strategies for the treatment of
      cardiovascular diseases by tissue-specific, selective activation of estrogen
      dependent molecular pathways devoid of side effects seen with conventional
      hormone therapy.

PMID- 21742057
TI  - A zebrafish SKIV2L2-enhancer trap line provides a useful tool for the study of
      peripheral sensory circuit development.
AB  - The zebrafish is an ideal model for elucidating the cellular and molecular
      mechanisms that underlie development of the peripheral nervous system. A
      transgenic line that selectively labels all the sensory circuits would be a
      valuable tool for such investigations. In this study, we describe such a line:
      the enhancer trap zebrafish line Tg(SKIV2L2:gfp)(j1775) which expresses green
      fluorescent protein (gfp) in the peripheral sensory ganglia. We show that this
      transgene marks all peripheral ganglia and sensory nerves, beginning at the time
      when the neurons are first extending their processes, but does not label the
      efferent nerves. The trapped reporter is inserted just upstream of a previously
      poorly described gene: lhfpl4 on LG6. The expression pattern of this gene by in
      situ hybridization reveals a different, but overlapping, pattern of expression
      compared to that of the transgene. This pattern also does not mimic that of the
      gene (skiv2l2), which provided the promoter element in the construct. These
      findings indicate that reporter expression is not dictated by an endogenous
      enhancer element, but instead arises through an unknown mechanism. Regardless,
      this reporter line should prove to be a valuable tool in the investigation of
      peripheral nervous system formation in the zebrafish.

PMID- 21742058
TI  - Current perspectives on the phylogeny of Filoviridae.
AB  - Sporadic fatal outbreaks of disease in humans and non-human primates caused by
      Ebola or Marburg viruses have driven research into the characterization of these
      viruses with the hopes of identifying host tropisms and potential reservoirs.
      Such an understanding of the relatedness of newly discovered filoviruses may help
      to predict risk factors for outbreaks of hemorrhagic disease in humans and/or non
      human primates. Recent discoveries such as three distinct genotypes of Reston
      ebolavirus, unexpectedly discovered in domestic swine in the Philippines; as well
      as a new species, Bundibugyo ebolavirus; the recent discovery of Lloviu virus as
      a potential new genus, Cuevavirus, within Filoviridae; and germline integrations
      of filovirus-like sequences in some animal species bring new insights into the
      relatedness of filoviruses, their prevalence and potential for transmission to
      humans. These new findings reveal that filoviruses are more diverse and may have
      had a greater influence on the evolution of animals than previously thought.
      Herein we review these findings with regard to the implications for understanding
      the host range, prevalence and transmission of Filoviridae.

PMID- 21742059
TI  - Genetic variation in IL28RA is associated with the outcomes of HCV infection in a
      high-risk Chinese population.
AB  - Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral
      and host factors. This study aims to investigate the association of single
      nucleotide polymorphisms (SNPs) of IFNAR2, IL10RB, and IL28RA genes with
      susceptibility to HCV infection and resolution. Genotyping of IFNAR2, IL10RB, and
      IL28RA gene polymorphisms were performed using TaqMan(r) method from 552 patients
      with sero-positive anti-HCV and 421 uninfected controls. The distribution of
      IFNAR2 and IL10RB genotypes among the control, persistent infection, and
      spontaneous clearance groups did not differ. However, IL28RA-rs10903035 A allele
      was over-represented in persistent infection group when compared with uninfected
      controls and spontaneous clearance group, respectively (OR=1.54, 95%CI=1.23-1.92,
      P=0.004; OR=1.42, 95%CI=1.12-1.81, P=0.016), and AA genotype had a significant
      increased risk of persistent infection in different strata except for the females
      subgroup (P<0.05). IL28RA-rs11249006 GG genotype showed reduced susceptibility to
      persistent HCV infection (OR=0.53, 95%CI=0.31-0.91, P=0.044), and the protective
      effect was significantly different among subgroups stratified by age and likely
      source of infection (P<0.05). Besides, AG genotype had a significant negative
      effect on spontaneous clearance of HCV among young subjects (aged ?40) and
      patients infected with viral genotype-1 (P<0.05). Stratified analysis also showed
      that IL10RB-rs2834167 AG genotype was associated with an increased risk of
      persistent HCV infection in females, and GG genotype was associated with an
      increased risk of persistent HCV infection in females and patients with viral
      genotype non-1 (P<0.05). Haplotype analysis showed that IL28RA rs10903035
      rs11249006 haplotype GG played a protective effect for HCV infection (OR=0.21,
      95%CI=0.13-0.36, P<0.001; OR=0.20, 95%CI=0.12-0.34, P<0.001). This study
      indicates that two SNPs in IL28RA are correlated with susceptibility to HCV
      infection and spontaneous viral clearance, which implicates a primary role of
      IL28RA in the outcomes of HCV infection.

PMID- 21742060
TI  - Nutrient excess and altered mitochondrial proteome and function contribute to
      neurodegeneration in diabetes.
AB  - Diabetic neuropathy is a major complication of diabetes that results in the
      progressive deterioration of the sensory nervous system. Mitochondrial
      dysfunction has been proposed to play an important role in the pathogenesis of
      the neurodegeneration observed in diabetic neuropathy. Our recent work has shown
      that mitochondrial dysfunction occurs in dorsal root ganglia (DRG) sensory
      neurons in streptozotocin (STZ) induced diabetic rodents. In neurons, the
      nutrient excess associated with prolonged diabetes may trigger a switching off of
      AMP kinase (AMPK) and/or silent information regulator T1 (SIRT1) signaling
      leading to impaired peroxisome proliferator-activated receptor gamma coactivator
      1 (PGC-1alpha) expression/activity and diminished mitochondrial activity. This
      review briefly summarizes the alterations of mitochondrial function and proteome
      in sensory neurons of STZ-diabetic rodents. We also discuss the possible
      involvement of AMPK/SIRT/PGC-1alpha pathway in other diabetic models and
      different tissues affected by diabetes.

PMID- 21742061
TI  - The altered activity of complex III may contribute to the high penetrance of
      Leber's hereditary optic neuropathy in a Chinese family carrying the ND4 G11778A
      mutation.
AB  - The ND4 G11778A mutation is the most common mitochondrial DNA mutation leading to
      Leber's hereditary optic neuropathy (LHON). Despite considerable clinical
      evidences, the modifier role of nuclear background and mitochondrial haplotypes
      in phenotypic manifestation of LHON remains poorly understood. We investigated
      the effect of these modifiers on bioenergetics in lymphoblastoid cell lines
      derived from five affected subjects of one Chinese family carrying the G11778A
      mutation and five Chinese controls. Significant reductions in the activities of
      complexes I and III were observed in mutant cell lines from the Chinese family,
      whereas the mutant cell lines from other families carrying the same mutation
      exhibited only reduced activity of complex I. The reduced activities of complexes
      I and III caused remarkably higher reductions of ATP synthesis in mutant cell
      lines from the Chinese family than those from other families. The deficient
      respiration increased generation of reactive oxygen species. The defect in
      complex III activity, likely resulting from the mitochondrial haplotype or
      nuclear gene alteration, worsens mitochondrial dysfunction caused by the G11778A
      mutation, thereby causing extremely high penetrance and expressivity of optic
      neuropathy in this Chinese family. Our data provide the first experimental
      evidence that altered activity of complex III modulates the phenotypic
      manifestation of LHON-associated G11778A mutation. Thus, our findings may provide
      new insights into the pathophysiology of LHON.

PMID- 21742062
TI  - Control of mitochondrial volume by mitochondrial metabolic water.
AB  - It is well-known that mitochondrial volume largely controls mitochondrial
      functioning. We investigate whether metabolic water produced by oxidative
      phosphorylation could be involved in mitochondrial volume regulation. We
      modulated the generation of this water in liver mitochondria and assess their
      volume by two independent techniques. In liver mitochondria, the mitochondrial
      volume was specifically decreased when no water was produced independently of
      energetic parameters and uncoupling activity. In all other conditions associated
      with water generation, there was no significant change in mitochondrial metabolic
      volume. Altogether these data demonstrate that mitochondrial volume is regulated,
      independently of energetic status, by the mitochondrial metabolic water that acts
      as a signal.

PMID- 21742063
TI  - Effect of selenite on basic mitochondrial function in human osteosarcoma cells
      with chronic mitochondrial stress.
AB  - Mitochondrial chronic stress that originates from defective mitochondria is
      implicated in a growing list of human diseases. To enhance understanding of
      pathophysiology of chronic mitochondrial dysfunction we investigated human
      osteosarcoma cells with 2 types of chronic stress: corresponding to the mutation
      in ATP synthase subunit 6 encoded by mtDNA (NARP syndrome-mild stress) and to a
      total lack of mtDNA (Rho0 cells-heavy stress). We previously found that selenium
      influenced mitochondrial stress response and lowered ROS production. Therefore,
      in this study effect of selenite on other mitochondrial parameters was
      investigated. We showed that presence of selenium improved survival of starved
      cells, modified organization of mitochondrial network in NARP cybrids and
      decreased cytosolic calcium level in NARP and Rho0 cells. Selenium did not affect
      mitochondrial membrane potential, ATP level, activity of ATP synthase and
      activity of complex II of the respiratory chain.

PMID- 21742064
TI  - Dynamic mechanical response of brain tissue in indentation in vivo, in situ and
      in vitro.
AB  - Characterizing the dynamic mechanical properties of brain tissue is deemed
      important for developing a comprehensive knowledge of the mechanisms underlying
      brain injury. The results gathered to date on the tissue properties have been
      mostly obtained in vitro. Learning how these results might differ quantitatively
      from those encountered in vivo is a critical step towards the development of
      biofidelic brain models. The present study provides novel and unique experimental
      results on, and insights into, brain biorheology in vivo, in situ and in vitro,
      at large deformations, in the quasi-static and dynamic regimes. The nonlinear
      dynamic response of the cerebral cortex was measured in indentation on the
      exposed frontal and parietal lobes of anesthetized porcine subjects. Load-unload
      cycles were applied to the tissue surface at sinusoidal frequencies of 10, 1, 0.1
      and 0.01 Hz. Ramp-relaxation tests were also conducted to assess the tissue
      viscoelastic behavior at longer times. After euthanasia, the indentation test
      sequences were repeated in situ on the exposed cortex maintained in its native
      configuration within the cranium. Mixed gray and white matter samples were
      subsequently excised from the superior cortex to be subjected to identical
      indentation test segments in vitro within 6-7 h post mortem. The main response
      features (e.g. nonlinearities, rate dependencies, hysteresis and conditioning)
      were measured and contrasted in vivo, in situ and in vitro. The indentation
      response was found to be significantly stiffer in situ than in vivo. The
      consistent, quantitative set of mechanical measurements thereby collected
      provides a preliminary experimental database, which may be used to support the
      development of constitutive models for the study of mechanically mediated
      pathways leading to traumatic brain injury.

PMID- 21742065
TI  - Synthesis and characterization of hierarchically macroporous and mesoporous CaO
      MO-SiO(2)-P(2)O(5) (M=Mg, Zn, Sr) bioactive glass scaffolds.
AB  - Mg-, Zn- and Sr-doped hierarchically macroporous and mesoporous CaO-MO-SiO(2)
      P(2)O(5) (M=Mg, Zn or Sr) bioactive glass (HMMBG) scaffolds were synthesized
      using the non-ionic block copolymer EO(20)PO(70)EO(20) and polyurethane sponges
      as cotemplates. The Mg-, Zn- or Sr-doped HMMBG scaffolds showed no distinct
      difference in phase composition, macroporous structure or pore volume from the
      HMMBG scaffolds without Mg, Zn or Sr. The Mg-, Zn- and Sr-doped HMMBG scaffolds
      showed no cytotoxicity. The gradual release of Ca, P, Si, Mg, Zn and Sr into the
      culture medium from these scaffolds contributed to the enhancement of the
      proliferation and ALP activity of mesenchymal stem cells (MSCs). The Mg-, Zn- and
      Sr-doped HMMBG scaffolds may be used as bone substitute materials.

PMID- 21742066
TI  - Novel protein-loaded chondroitin sulfate-chitosan nanoparticles: preparation and
      characterization.
AB  - In this study, the potential of chondroitin sulfate (ChS)-chitosan (CS)
      nanoparticles (NPs) for the delivery of proteins was investigated. ChS-CS NPs
      were prepared by ionic cross-linking of CS solution with ChS. The aggregation
      line, particle size and zeta potential were investigated as a function of the pH,
      weight ratio and concentration. The water content and formation yield of the NPs
      were measured by gravimetry. Results indicated that ChS-CS NPs showed a higher
      degree of ionic cross-linking and formation yield than sodium tripolyphosphate-CS
      NPs. Fluorescein isothiocyanate conjugate bovine serum albumin (FITC-BSA), a
      model protein drug, was incorporated into the ChS-CS NPs. The encapsulation
      efficiency was obviously increased with the increase in initial FITC-BSA
      concentration and was as high as 90%. In vitro release studies of ChS-CS NPs
      showed a small burst effect following a continued and controlled release.
      Cytotoxicity tests with Caco-2 cells showed no toxic effects of ChS-CS NPs. The
      ex vivo cellular uptake studies using Caco-2 and HEK-293 cells indicated that NPs
      were found to be endocytosed into the cells. In conclusion, ChS-CS NPs are a
      potential new delivery system for the transport of hydrophilic compounds such as
      proteins.

PMID- 21742067
TI  - The effects of intermittent dynamic loading on chondrogenic and osteogenic
      differentiation of human marrow stromal cells encapsulated in RGD-modified
      poly(ethylene glycol) hydrogels.
AB  - Biochemical and biomechanical cues are known to influence the differentiation of
      stem cells. Biomechanical cues arise from cellular interactions with their
      surrounding matrix and from applied forces. This study investigates the role of
      biomechanical cues in chondrogenic and osteogenic differentiation of human marrow
      stromal cells (hMSC) when encapsulated in synthetic hydrogels. Poly(ethylene
      glycol) hydrogels were fabricated with tethered cell adhesion moieties, RGD. Cell
      laden hydrogels were subjected to 4 h daily intermittent dynamic compressive
      loading (0.3Hz, 15% amplitude strain) for up to 14 days and the cell response
      evaluated by gene expression and matrix deposition for chondrogenic and
      osteogenic markers. The three-dimensional hydrogel supported chondrogenesis and
      osteogenesis under free swelling conditions, as shown by the up-regulation of
      cartilage-related markers (SOX9, Col II, Col X, and aggrecan) and staining for
      type II collagen and aggrecan and osteogenically by up-regulation of ALP and
      staining for type I collagen and for mineralization. However, under dynamic
      loading the expression of cartilage-related markers SOX9, Col II, Col X, and
      aggrecan were down-regulated, along with reduced aggrecan staining and no
      positive staining for type II collagen. Additionally, the bone-related markers
      RUNX2, Col I, and ALP were down-regulated and positive staining for type I
      collagen and mineralization was reduced. In conclusion, the selected loading
      regime appears to have an inhibitory effect on chondrogenesis and osteogenesis of
      hMSC encapsulated in PEG-RGD hydrogels after 14 days in culture, potentially due
      to overloading of the differentiating hMSC before sufficient pericellular matrix
      is produced and/or due to large strains, particularly for osteogenically
      differentiating hMSC.

PMID- 21742068
TI  - Triggered disassembly of hierarchically assembled onion-like micelles into the
      pristine core-shell micelles via a small change in pH.
AB  - The size and surface property of nanomaterial-based delivery systems administered
      intravenously play important roles in their cell uptake and in vivo distribution.
      Both of them should be capable of self-evolution in order to achieve efficient
      targeting performance. A facile strategy was proposed to manipulate both the size
      and surface property of polymeric micelles. It was found that the hierarchical
      assembly between trimethylated chitosan-g-poly(epsilon-caprolactone) (TMC-PCL)
      micelles and carboxyethyl chitosan-g-poly(ethylene glycol) (CEC-PEG) could
      produce onion-like micelles with enlarged size and PEGylated surface. The onion
      like micelles could withstand the ionic strength of plasma and competitive
      exchange with BSA, and abruptly disassemble into the pristine TMC-PCL micelles
      via a small change in pH. By varying the degree of carboxyethylation, the
      disassembly pH could be modulated to the range of the tumoral microclimate pH. In
      contrast with TMC-PCL micelles, which displayed high cytotoxicity and endocytic
      ability towards C6 glioma cells, the onion-like micelles were cell-friendly and
      internalized by the cells at a very low level. Doxorubicin was used as a model
      chemotherapeutic agent and incorporated within TMC-PCL micelles. Dox release from
      both TMC-PCL micelles and the onion-like micelles was very slow under normal
      physiological conditions and displayed excellent pH sensitivity. Cell viability
      of Dox-loaded micelles was also investigated.

PMID- 21742069
TI  - Diversity of anti-haemostatic proteins in the salivary glands of Rhodnius species
      transmitters of Chagas disease in the greater Amazon.
AB  - The triatomines in the tribe Rhodniini are the main vectors of the Trypanosoma
      cruzi to humans in recent outbreaks of acute Chagas disease in the Amazon. These
      insects dwelling in palm trees do not colonize the human domicile. Their success
      to transmit the infection relies partially on the efficacy of their salivary
      gland apparatuses. Here we show the transcriptome of the Rhodnius brethesi and
      Rhodnius robustus salivary glands, comprising 56 and 122 clusters, respectively.
      Approximately one third of these clusters are described for the first time. The
      LC-MS/MS analysis identified 123 and 111 proteins in R. brethesi and R. robustus
      sialome, respectively. Noteworthy, lipocalin platelet aggregation inhibitors,
      inositol polyphosphate 5-phosphatases, and Kazal domain proteins, which are
      essential for the insect's successful acquisition of blood meals, were found in
      our analysis. Moreover, glutathione S transferase and antigen-5, which play roles
      in the insect's defense and resistance against insecticide, were also observed.

PMID- 21742070
TI  - Prolonged bisphosphonate release after treatment in women with osteoporosis.
      Relationship with bone turnover.
AB  - Bisphosphonates (BP), especially alendronate and risedronate, are the drugs most
      commonly used for osteoporosis treatment, being incorporated into the skeleton
      where they inhibit bone resorption and are thereafter slowly released during bone
      turnover. However, there are few data on the release of BP in patients who have
      received treatment with these drugs for osteoporosis. This information is
      essential for evaluating the possibility of BP cyclic therapy in these patients
      and for controlling their long-term presence in bone tissue. This study evaluated
      the urinary excretion of alendronate and risedronate in patients treated with
      these drugs for osteoporosis and analysed its relationship with bone turnover,
      time of previous drug exposure and time of treatment discontinuation. We included
      43 women (aged 65+/-9.4 years) previously treated with alendronate (36) or
      risedronate (7) during a mean of 51+/-3 and 53+/-3 months, respectively, who had
      not been treated with other antiosteoporotic treatment and with a median time of
      discontinuation of 13.5 and 14 months, respectively. Both BP were detected in 24
      hour urine by HPLC. In addition, bone formation (PINP) and resorption (NTx)
      markers were analysed. Both BP were also determined in a control group of women
      during treatment. Alendronate was detected in 41% of women previously treated
      with this drug whereas no patient previously treated with risedronate showed
      detectable urinary values. All control patients showed detectable values of both
      BP. In patients with detectable alendronate levels, the time of drug cessation
      was shorter than in patients with undetectable values (12 [6-19] versus 31 [7-72]
      months, p<0.001). Alendronate was not detected in any patient 19 months after
      treatment cessation. Alendronate levels were inversely related to time of
      treatment discontinuation (r=-0.403, p=0.01) and the latter was directly related
      to NTx (r=0.394, p=0.02). No relationship was observed with age, length of drug
      exposure, renal function or weight. In conclusion, contrary to risedronate, which
      was not detected in patients after cessation of treatment, alendronate was
      frequently detected in women previously treated with this agent up to 19 months
      after discontinuation of therapy. The relationship between alendronate levels and
      both bone resorption and time of treatment cessation further indicates a residual
      effect of this drug in bone, despite treatment discontinuation.

PMID- 21742071
TI  - Ronacaleret, a calcium-sensing receptor antagonist, has no significant effect on
      radial fracture healing time: results of a randomized, double-blinded, placebo
      controlled Phase II clinical trial.
AB  - BACKGROUND: Fractures cause significant morbidity, mortality, and use of health
      care resources. An oral agent that enhances fracture healing could reduce costs
      and prevent future disabilities. In Phase I studies, ronacaleret, a novel calcium
      sensing receptor antagonist, stimulated parathyroid hormone (PTH) release and
      increased bone formation markers, suggesting that it may act as an effective oral
      anabolic agent to enhance fracture healing. METHODS: This was a randomized,
      double-blind, placebo-controlled, parallel-group, clinical trial in 85 male and
      female subjects who had sustained a closed, unilateral, extra-articular fracture
      of the distal radius and were receiving conservative treatment. Subjects were
      randomly assigned in a double-blind manner to ronacaleret 200 mg twice daily,
      ronacaleret 400 mg once daily or matching placebo and followed for 12 weeks.
      Fracture healing was assessed by radiographs and quantitative computed tomography
      (CT), and bone turnover markers were measured. The study was terminated early for
      futility based on the results of an unplanned interim analysis. RESULTS: There
      were no significant differences between treatment groups in time to radiographic
      fracture healing (74, 65 and 68 days for placebo, 200 mg twice daily and 400 mg
      once daily dose groups, respectively), cortical bridging, grip strength, pain and
      swelling, time to cast removal, or range of motion. Markers of bone formation and
      levels of whole PTH, intact PTH and serum calcium increased following treatment
      with ronacaleret. CONCLUSION: Ronacaleret had no significant effect on duration
      of healing by radiograph or CT scan, time to cast removal, clinical symptoms,
      grip strength, or range of motion.

PMID- 21742072
TI  - The role of pressurized fluid in subchondral bone cyst growth.
AB  - Pressurized fluid has been proposed to play an important role in subchondral bone
      cyst development. However, the exact mechanism remains speculative. We used an
      established computational mechanoregulated bone adaptation model to investigate
      two hypotheses: 1) pressurized fluid causes cyst growth through altered bone
      tissue loading conditions, 2) pressurized fluid causes cyst growth through
      osteocyte death. In a 2D finite element model of bone microarchitecture, a marrow
      cavity was filled with fluid to resemble a cyst. Subsequently, the fluid was
      pressurized, or osteocyte death was simulated, or both. Rather than increasing
      the load, which was the prevailing hypothesis, pressurized fluid decreased the
      load on the surrounding bone, thereby leading to net bone resorption and growth
      of the cavity. In this scenario an irregularly shaped cavity developed which
      became rounded and obtained a rim of sclerotic bone after removal of the
      pressurized fluid. This indicates that cyst development may occur in a step-wise
      manner. In the simulations of osteocyte death, cavity growth also occurred, and
      the cavity immediately obtained a rounded shape and a sclerotic rim. Combining
      both mechanisms increased the growth rate of the cavity. In conclusion, both
      stress-shielding by pressurized fluid, and osteocyte death may cause cyst growth.
      In vivo observations of pressurized cyst fluid, dead osteocytes, and different
      appearances of cysts similar to our simulation results support the idea that both
      mechanisms can simultaneously play a role in the development and growth of
      subchondral bone cysts.

PMID- 21742073
TI  - Optimizing electrocardiographic interpretation in acute ST-elevation myocardial
      infarction may be very beneficial.

PMID- 21742074
TI  - Regarding "The EVEREST II Trial: design and rationale for a randomized study of
      the Evalve MitraClip system compared with mitral valve surgery for mitral
      regurgitation".

PMID- 21742076
TI  - Liver transaminase levels alone could not be the optimal method to estimate
      hepatic safety after statin administration in patients with chronic kidney
      disease.

PMID- 21742077
TI  - Standard versus high loading doses of clopidogrel in Asian patients with ST
      segment elevation myocardial infarction undergoing percutaneous coronary
      intervention: insights from the Korea Acute Myocardial Infarction Registry.

PMID- 21742078
TI  - Do East Asians have different hypercoagulable states compared with Western
      population?

PMID- 21742080
TI  - Appropriate cardiac catheterization laboratory activation: optimizing
      electrocardiogram interpretation and clinical decision making for acute ST
      elevation myocardial infarction.

PMID- 21742082
TI  - Acute hyperglycemia: is really a new risk marker for contrast-induced nephropathy
      in patients with acute myocardial infarction without diabetes and normal renal
      function?

PMID- 21742084
TI  - Geographic variations of acute heart failure syndromes: the importance of
      clinical registries.

PMID- 21742085
TI  - Phase II trials in heart failure: the role of cardiovascular imaging.
AB  - The development of new therapies for heart failure (HF), especially acute HF, has
      proven to be quite challenging; and therapies evaluated in HF have greatly
      outnumbered treatments that are eventually successful in obtaining regulatory
      approval. Thus, the development of therapies for HF remains a vexing problem for
      pharmaceutical and device companies, clinical trialists, and health care
      professionals. Nowhere is this more apparent than in the phase II HF clinical
      trial, in which the goal is to determine whether an investigational agent should
      move forward to a phase III trial. Recent advancements in noninvasive
      cardiovascular imaging have allowed a new era of comprehensive phenotyping of
      cardiac structure and function in phase II HF trials. Besides using imaging
      parameters to predict success of subsequent phase III outcome studies, it is
      essential to also use imaging in phase II HF trials in a way that increases
      understanding of drug or device mechanism. Determination of the patients who
      would benefit most from a particular drug or device could decrease heterogeneity
      of phase III trial participants and lead to more successful HF clinical trials.
      In this review, we outline advantages and disadvantages of imaging various
      aspects of cardiac structure and function that are potential targets for therapy
      in HF, compare and contrast imaging modalities, provide practical advice for the
      use of cardiovascular imaging in drug development, and conclude with some novel
      uses of cardiac imaging in phase II HF trials.

PMID- 21742086
TI  - Ischemic heart disease: comprehensive evaluation by cardiovascular magnetic
      resonance.
AB  - Considerable technical advances over the past decade have increased the clinical
      application of cardiovascular magnetic resonance (CMR) imaging. A comprehensive
      CMR examination can accurately measure left and right ventricular size and
      function, identify the presence and extent of reversible versus irreversible
      myocardial injury, and detect inducible ischemia. Streamlined protocols allow
      such a CMR examination to be a time-efficient diagnostic tool in patients with
      coronary artery disease. Moreover, edema imaging with T2-weighted CMR allows the
      detection of acute coronary syndromes. In this review, we present the relevant
      CMR methods and discuss practical uses of CMR in acute and chronic ischemic heart
      disease.

PMID- 21742087
TI  - Differential impact of race and risk factors on incidence of atrial fibrillation.
AB  - Despite some common risk factors for atrial fibrillation (AF) being more
      prevalent among blacks, African Americans are increasingly being reported with
      lower prevalence and incidence of AF compared with whites. Contemporary studies
      have not provided a complete explanation for this apparent AF paradox in African
      Americans. Although many traditional and novel risk factors for AF have been
      identified, the role of ethnic-specific risk factors has not been examined.
      Whereas hypertension has been the most common risk factor associated with AF,
      coronary artery disease also plays an important role in AF pathophysiology in
      whites. Thereby, elucidating the role of ethnic-specific risk factors for AF may
      provide important insight into why African Americans are protected from AF or why
      whites are more prone to develop the arrhythmia. The link between AF
      susceptibility and genetic processes has only been recently uncovered.
      Polymorphisms in renin-angiotensin system genes have been characterized as
      predisposing to AF under certain environmental conditions. Several ion channel
      genes, signaling molecules, and several genetic loci have been linked with AF.
      Thereby, studies investigating genetic variants contributing to the differential
      AF risk in individuals of African American versus European ancestry may also
      provide important insight into the etiology of the AF paradox in blacks.

PMID- 21742088
TI  - Diagnosis and management issues in thoracic aortic aneurysm.
AB  - Thoracic aortic enlargement is an increasingly recognized condition that is often
      diagnosed on imaging studies performed for unrelated indications. The risk of
      unrecognized and untreated aortic enlargement and aneurysm includes aortic
      rupture and dissection which carry a high burden of morbidity and mortality. The
      etiologies underlying thoracic aortic enlargement are diverse and can range from
      degenerative or hypertension associated aortic enlargement to more rare genetic
      disorders. Therefore, the evaluation and management of these patients can be
      complex and requires knowledge of the pathophysiology associated with thoracic
      aortic dilation and aneurysm. Additionally, there have been important advances in
      the treatment available to patients with thoracic aortic disease, including an
      increased role of endovascular therapy. Given the risk of mortality, increased
      clinical recognition and advances in therapeutics, the American College of
      Cardiology, American Heart Association and related professional societies have
      recently published guidelines on the management of thoracic aortic disease. This
      review focuses on the pathophysiology and various etiologies that lead to
      thoracic aortic aneurysm along with the diagnostic modalities and management of
      asymptomatic patients with thoracic aortic disease.

PMID- 21742089
TI  - A multicenter, randomized, controlled study of mechanical left ventricular
      unloading with counterpulsation to reduce infarct size prepercutaneous coronary
      intervention for acute myocardial infarction: rationale and design of the
      Counterpulsation Reduces Infarct Size Acute Myocardial Infarction trial.
AB  - BACKGROUND: Despite advances in care processes to improve reperfusion in patients
      with acute myocardial infarction (AMI), the short-term and 1-year mortality
      remains high, in part, because of reperfusion injury, microvascular obstruction,
      and infarct expansion. Intraaortic balloon counterpulsation (IABC) is an adjunct
      to revascularization and has reduced microvascular obstruction and infarct size
      in animal models of AMI. METHODS: CRISP AMI is a multicenter randomized trial
      that aims to determine if IABC initiated before percutaneous coronary
      intervention (PCI) for reperfusion compared with routine PCI in patients with
      anterior ST-segment elevation AMI reduces infarct size as measured by cardiac
      magnetic resonance imaging. Patients are randomly assigned to receive IABC
      initiated before primary PCI and continued for at least 12 hours or routine PCI
      with standard-of-care medical therapy in both groups. The primary efficacy end
      point is infarct size measured by cardiac magnetic resonance imaging at 3 to 5
      days post-PCI. The secondary clinical end point is the composite of major adverse
      clinical events including death, reinfarction, and heart failure at 6 months.
      According to sample size calculation, 300 patients will be randomized at 50 sites
      across 10 countries. CONCLUSION: The CRISP AMI study will determine if IABC
      before reperfusion in patients with anterior AMI reduces infarct size.

PMID- 21742090
TI  - The omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation
      trial--rationale and design.
AB  - Postoperative atrial fibrillation/flutter (PoAF) commonly complicates cardiac
      surgery, occurring in 25% to 60% of patients. Postoperative atrial
      fibrillation/flutter is associated with significant morbidity, higher long-term
      mortality, and increased health care costs. Novel preventive therapies are
      clearly needed. In experiments and short-term trials, seafood-derived long-chain
      omega-3 polyunsaturated fatty acids (PUFAs) influence several risk factors that
      might reduce risk of PoAF. A few small and generally underpowered trials have
      evaluated effects of omega-3-PUFAs supplementation on PoAF with mixed results.
      The OPERA trial is an appropriately powered, investigator-initiated, randomized,
      double-blind, placebo-controlled, multinational trial to determine whether
      perioperative oral omega-3-PUFAs reduces occurrence of PoAF in patients
      undergoing cardiac surgery. Additional aims include evaluation of resource use,
      biologic pathways and mechanisms, postoperative cognitive decline, and safety.
      Broad inclusion criteria encompass a "real-world" population of outpatients and
      inpatients scheduled for cardiac surgery. Treatment comprises a total
      preoperative loading dose of 8 to 10 g of omega-3-PUFAs or placebo divided over 2
      to 5 days, followed by 2 g/d until hospital discharge or postoperative day 10,
      whichever comes first. Based on anticipated 30% event rate in controls, total
      enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to
      detect 25% reduction in PoAF. The OPERA trial will provide invaluable evidence to
      inform biologic pathways; proof of concept that omega-3-PUFAs influence cardiac
      arrhythmias; and potential regulatory standards and clinical use of this simple,
      inexpensive, and low-risk intervention to prevent PoAF.

PMID- 21742091
TI  - Troponin measurements during drug development--considerations for monitoring and
      management of potential cardiotoxicity: an educational collaboration among the
      Cardiac Safety Research Consortium, the Duke Clinical Research Institute, and the
      US Food and Drug Administration.
AB  - Drug-induced cardiac toxicity is a recognized challenge in development and
      implementation of pharmacotherapy. Appropriate biomarkers are needed to detect
      these abnormalities early in development and to manage the risk of potentially
      cardiotoxic drugs or biologic agents. Circulating cardiac troponin (cTn) is the
      most widely used biomarker for detection of myocardial injury. Although most
      commonly used to detect myonecrosis in the setting of ischemia, cTns are also
      elevated with other acute and chronic disease processes, including heart failure,
      renal failure, sepsis, pulmonary embolic disease, and many others. High
      sensitivity assays for both cTnI and cTnT are now available that achieve
      acceptable imprecision (coefficient of variation <10%) at the 99th percentile of
      a normal reference population. Even more sensitive assays are being developed
      that detect cTn in ranges that are near the level of normal cellular turnover
      (apoptosis). These properties of cTn and the continuing evolution of highly
      sensitive assays position cTn as a potentially uniquely informative marker for
      early detection of cardiac toxicity. This article summarizes collaborative
      discussions among key stakeholders in the Cardiac Safety Research Consortium
      about the use of cTn monitoring in drug development.

PMID- 21742092
TI  - Prevalence and correlates of smoking cessation pharmacotherapy in hospitalized
      smokers with acute myocardial infarction.
AB  - BACKGROUND: Although current performance measures recommend smoking cessation
      counseling at the time of acute myocardial infarction (AMI), the American College
      of Cardiology/American Heart Association guidelines recommend pharmacotherapy as
      well. The aim of this study was to describe the prevalence and correlates of
      smoking cessation pharmacotherapy in hospitalized patients with AMI. METHODS: In
      the 24-center TRIUMPH registry, 4,340 AMI patients underwent detailed interviews;
      and 1,631 reported smoking within 30 days of admission. Prescription of first
      line smoking cessation medications at discharge was assessed by medical record
      review. All patient-related factors associated with smoking cessation treatment,
      based on literature review, were included in hierarchical modified log Poisson
      models. RESULTS: Only 14% (222/1,631) of AMI patients who smoked were prescribed
      smoking cessation medication at discharge. After multivariable adjustment for
      patient characteristics, there was significant variation across sites (range 0%
      28%, median rate ratio 1.41, 95% CI 1.23-2.67). Independent factors associated
      with smoking cessation pharmacotherapy included older age (rate ratio 0.81 per 10
      year increment, 95% CI 0.71-0.93), high school graduation (rate ratio 1.37, 95%
      CI 1.10-1.66), heavy cigarette usage (>20/d) (rate ratio 3.08, 95% CI 2.20-4.12),
      in-hospital revascularization (rate ratio 1.41, 95% CI 1.0-1.94), and
      instructions on smoking cessation (rate ratio 2.37, 95% CI 1.40-4.01).
      CONCLUSIONS: Smokers surviving an AMI are infrequently prescribed guideline
      recommended smoking cessation treatments, and there is considerable variation
      across hospitals. Older, less educated, and lighter smokers are less likely to
      receive aggressive smoking cessation treatment. Novel strategies to augment
      current practice are needed.

PMID- 21742093
TI  - Improved diagnostic and prognostic performance of a new high-sensitive troponin T
      assay in patients with acute coronary syndrome.
AB  - BACKGROUND: In the present study, we aimed to analyze the diagnostic and
      prognostic potential of a newly developed high-sensitive troponin T assay and
      compared these results with those of a contemporary troponin T assay in 2
      distinct patient cohorts, one including patients with evident ACS and the other
      one including patients with general chest pain. METHODS AND RESULTS: For this
      study, we analyzed data from 2 independent patient cohorts, the Bad Nauheim ACS
      registry and the Prognosis in Acute Coronary Syndromes registry, with a total of
      2,506 patients. On admission, clinical data have been recorded, and a single
      measurement of troponin T has been performed with a contemporary assay (TnT) and
      a new high-sensitive troponin T assay (hsTnT). Clinical follow-up has been
      obtained after 6 months. The diagnostic value of hsTnT was superior to TnT (area
      under the receiver operating characteristic curve 0.949 vs 0.929, P = .016).
      Specifically, in TnT-negative patients, hsTnT provided strong diagnostic
      information (area under the receiver operating characteristic curve of 0.81, P <
      .001). Furthermore, hsTnT provided independent prognostic power for mortality
      within 6 months in both cohorts, which was superior to that of the contemporary
      TnT assay. CONCLUSION: Troponin T measured with a newly developed hsTnT provides
      better diagnostic and prognostic information and, therefore, should be
      implemented as a standard test in clinical routine.

PMID- 21742094
TI  - Cardiogenic shock and heart failure post-percutaneous coronary intervention in ST
      elevation myocardial infarction: observations from "Assessment of Pexelizumab in
      Acute Myocardial Infarction".
AB  - BACKGROUND: Mortality after ST-elevation myocardial infarction (STEMI) has
      reduced with reperfusion by primary percutaneous coronary intervention (PCI),
      which may have impacted on the adverse outcomes of cardiogenic shock (CS) and
      congestive heart failure (CHF). METHODS AND RESULTS: In the APEX-AMI trial, 5,745
      patients with STEMI and planned primary PCI were randomly assigned pexelizumab or
      matching placebo. Post-randomization CS or CHF was adjudicated by a clinical
      endpoints committee. Treatment assignment to pexelizumab did not influence either
      endpoint or mortality rates. Cardiogenic shock developed in 196 patients (3.4%)
      at a median of 6.0 hours (interquartile range 3.9-28.3) post-randomization, and
      mortality at 90 days was 54.6%. Congestive heart failure occurred in 254 of
      patients (4.4%) at a median of 2.6 days (IQR 1.0-16.6), and mortality through 90
      days was 10.2%; mortality among those with neither endpoint was 2.1%. Patients
      with CS or CHF were older, were more often female, and had more hypertension and
      diabetes, but smoked less compared with non-CS/CHF patients (all P < .05).
      Independent mortality predictors among those with CS or CHF were hyperlipidemia
      and a history of angina (interaction P = .011 and .008, respectively); procedural
      predictors among survivors to PCI were pre-PCI Thrombolysis In Myocardial
      Infarction (TIMI) flow 0-1 and post-PCI TIMI flow <3 (P = .013 and <.0001,
      respectively). CONCLUSIONS: Survival after CS remains poor despite aggressive
      reperfusion. Both CS and CHF remain the major causes of death among STEMI
      patients undergoing primary PCI. Future studies should examine treatments that
      aim to reduce mortality in these highest risk patients.

PMID- 21742095
TI  - Bleeding, mortality, and antiplatelet therapy: results from the Clopidogrel for
      High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance
      (CHARISMA) trial.
AB  - BACKGROUND: The association between bleeding severity and cause of mortality in
      the non-acute setting is unclear. We sought to investigate the association
      between bleeding and mortality subtype, and assess whether this association
      differs in patients on dual antiplatelet therapy (DAPT) versus aspirin alone.
      METHODS: Using multivariable Cox proportional hazards survival regression, we
      examined the association between moderate or severe bleeding and all-cause,
      cardiovascular, and cancer mortality in 15,603 patients with cardiovascular
      disease or multiple risk factors enrolled in the CHARISMA trial. RESULTS:
      Patients with moderate or severe bleeding had a higher incidence of all-cause,
      cardiovascular, and cancer mortality (P < .001 for each). After multivariable
      adjustment, moderate/severe bleeding remained independently associated with not
      only all-cause mortality (adjusted hazard ratio [HR] 1.66; 95% confidence
      interval [CI] 1.24-2.21) and cardiovascular mortality (HR 2.05, 95% CI 1.38-3.04)
      but also cancer mortality (HR 4.76, 95% CI 2.60-8.69). However, there was a
      significant interaction between bleeding and potency of antiplatelet therapy for
      all-cause (P = .002), cardiovascular (P = .02), and cancer mortality (P = .03);
      in subjects on aspirin alone, moderate/severe bleeding was associated with all
      cause (HR 5.27, 95% CI 3.56-7.80), cardiovascular (HR 4.33, 95% CI 2.55-7.37),
      and cancer mortality (HR 9.01, 95% CI 4.41-18.43), but not in subjects on DAPT
      (all-cause: HR 1.48, 95% CI 0.93-2.34; cardiovascular: HR 1.04, 95% CI 0.58-1.86;
      and cancer mortality: HR 1.79, 95% CI 0.56-5.74). CONCLUSIONS: In stable
      patients, moderate or severe bleeding is associated with a significantly
      increased risk of all-cause, cardiovascular, and cancer mortality. However, this
      risk appeared different in subjects on single antiplatelet therapy versus DAPT.

PMID- 21742096
TI  - Race, ethnicity, and the efficacy of rosuvastatin in primary prevention: the
      Justification for the Use of Statins in Prevention: an Intervention Trial
      Evaluating Rosuvastatin (JUPITER) trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of statin treatment
      in primary prevention of cardiovascular events in different race/ethnic groups.
      BACKGROUND: Clinical trial evidence about the efficacy of statins in the primary
      prevention of cardiovascular events among nonwhites is uncertain. METHODS:
      JUPITER trial, a randomized, double-blind, placebo-controlled evaluation of
      rosuvastatin 20 mg in the primary prevention of myocardial infarction (MI),
      stroke, arterial revascularization, hospitalization for unstable angina, and
      cardiovascular death included 12,683 whites and 5,117 nonwhites with low-density
      lipoprotein levels <130 mg/dL and high-sensitivity C-reactive protein levels
      >=2.0 mg/L. RESULTS: Random allocation to rosuvastatin resulted in a 45%
      reduction in the primary end point among whites (hazard ratio [HR] 0.55, 95% CI
      0.43-0.69) and a 37% reduction among nonwhites (HR 0.63, 95% CI 0.41-0.99).
      Blacks (HR 0.65, 95% CI 0.35-1.22) and Hispanics (HR 0.58, 95% CI 0.25-1.39) had
      similar risk reductions. Among nonwhites in the placebo group, the stroke rate
      exceeded the MI rate (0.44 vs 0.20 per 100 person-years); an opposite pattern was
      observed among whites (0.31 vs 0.42 per 100 person-years). Nonwhites had higher
      death rates than whites (2.25 vs 0.93 per 100 person-years); however, all-cause
      mortality was similar at 20% with rosuvastatin treatment in both participant
      groups. CONCLUSIONS: When used in primary prevention among individuals with low
      density lipoprotein <130 mg/dL and high-sensitivity C-reactive protein >=2 mg/L,
      rosuvastatin significantly reduced first MI, stroke, arterial revascularization,
      hospitalization for unstable angina, and cardiovascular death among whites and
      nonwhites.

PMID- 21742097
TI  - Aspirin for the prevention of cardiovascular events in patients without clinical
      cardiovascular disease: a meta-analysis of randomized trials.
AB  - BACKGROUND: The benefit of aspirin to prevent cardiovascular events in subjects
      without clinical cardiovascular disease relative to the increased risk of
      bleeding is uncertain. METHODS: A meta-analysis of randomized trials of aspirin
      versus placebo/control to assess the effect of aspirin on major cardiovascular
      events (MCEs) (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular
      death), individual components of the MCE, stroke subtype, all-cause mortality,
      and major bleeding. Nine trials involving 102,621 patients were included: 52,145
      allocated to aspirin and 50,476 to placebo/control. RESULTS: Over a mean follow
      up of 6.9 years, aspirin was associated with a reduction in MCE (risk ratio [RR]
      0.90, 95% CI 0.85-0.96, P < .001). There was no significant reduction for
      myocardial infarction, stroke, ischemic stroke, or all-cause mortality. Aspirin
      was associated with hemorrhagic stroke (RR 1.35, 95% CI 1.01-1.81, P = .04) and
      major bleeding (RR 1.62, 95% CI 1.31-2.00, P < .001). In meta-regression, the
      benefits and bleeding risks of aspirin were independent of baseline
      cardiovascular risk, background therapy, age, sex, and aspirin dose. The number
      needed to treat to prevent 1 MCE over a mean follow-up of 6.9 years was 253 (95%
      CI 163-568), which was offset by the number needed to harm to cause 1 major bleed
      of 261 (95% CI 182-476). CONCLUSIONS: The current totality of evidence provides
      only modest support for a benefit of aspirin in patients without clinical
      cardiovascular disease, which is offset by its risk. For every 1,000 subjects
      treated with aspirin over a 5-year period, aspirin would prevent 2.9 MCE and
      cause 2.8 major bleeds.

PMID- 21742098
TI  - Practice variability and outcomes of coil embolization of aortopulmonary
      collaterals before Fontan completion: a report from the Pediatric Heart Network
      Fontan Cross-Sectional Study.
AB  - BACKGROUND: The practice of coiling aortopulmonary collaterals (APCs) before
      Fontan completion is controversial, and published data are limited. We sought to
      compare outcomes in subjects with and without pre-Fontan coil embolization of
      APCs using the Pediatric Heart Network Fontan Cross-Sectional Study database
      which enrolled survivors of prior Fontan palliation. METHODS: We compared
      hospital length of stay after Fontan in 80 subjects who underwent APC coiling
      with 459 subjects who did not. Secondary outcomes included post-Fontan
      complications and assessment of health status and ventricular performance at
      cross-sectional evaluation (mean 8.6 +/- 3.4 years after Fontan). RESULTS:
      Centers varied markedly in frequency of pre-Fontan APC coiling (range 0%-30% of
      subjects, P < .001). The coil group was older at Fontan (P = .004) and more
      likely to have single right ventricular morphology (P = .054) and pre-Fontan
      atrioventricular valve regurgitation (P = .03). The coil group underwent Fontan
      surgery more recently (P < .001), was more likely to have a prior superior
      cavopulmonary anastomosis (P < .001), and more likely to undergo extracardiac
      Fontan connection (P < .001) and surgical fenestration (P < .001). In
      multivariable analyses, APC coiling was not associated with length of stay
      (hazard ratio for remaining in-hospital 0.91, 95% CI 0.70-1.18, P = .48) or
      postoperative complications, except more post-Fontan catheter interventions
      (hazard ratio 1.74, 95% CI 1.04-2.91, P = .03), primarily additional APC coils.
      The groups had similar outcomes at cross-sectional evaluation. CONCLUSION:
      Management of APCs before Fontan shows marked practice variation. We did not find
      an association between pre-Fontan coiling of APCs and shorter postoperative
      hospital stay or with better late outcomes. Prospective studies of this practice
      are needed.

PMID- 21742099
TI  - Growth differentiation factor 15: an additional diagnostic tool for the risk
      stratification of developing heart failure in patients with operated congenital
      heart defects?
AB  - BACKGROUND: Many young adults who have congenital heart defects develop heart
      failure despite corrective surgeries. Growth differentiation factor 15 (GDF-15)
      has an established role as a marker for risk stratification and mortality both in
      patients after acute myocardial infarction and in patients with heart failure.
      Our aim was to establish a role for GDF-15 for monitoring heart failure in
      operated congenital heart defects (ACHD). This potential biomarker was validated
      through comparison with maximal oxygen uptake (VO(2max)) and to another
      biomarker, N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS: A total
      of 317 ACHD patients (129 females) with an average age of 26.5 +/- 8.5 years
      (mean +/- SD) enrolled in the study. We studied the relation between GDF-15 and
      NT-proBNP and VO(2max%) (percent predicted for age and gender). The cutoffs for
      the groups were as follows: NT-proBNP <100, 100 to 300, and >300 pg/mL; VO(2max%)
      <65%, 65% to 85%, and >85% of predicted normal. RESULTS: Significant differences
      in mean GDF-15 levels were found between the NT-proBNP <100 and NT-proBNP >300
      groups, as well as between the 100 to 300 and the >300 groups. For VO(2max%),
      significant differences were found in GDF-15 levels between <65% and >85% and
      between <65% and 65% to 85%, respectively. The lowest mean GDF-15 was found in
      groups with NT-proBNP <100 pg/mL and VO(2max%) >85%. The highest mean GDF-15 was
      found in the groups with NT-proBNP >300 pg/mL and VO(2max%) <65%. A subgroup
      analysis, including 82 patients with operated tetralogy of Fallot, showed that
      patients in the New York Heart Association I class have significantly lower NT
      proBNP and GDF-15 level and markedly higher VO(2max) compared with the patients
      in higher New York Heart Association class. CONCLUSION: Growth differentiation
      factor 15 might be used as a surrogate marker for latent heart failure and could
      help to identify patients with ACHD who are at risk for developing heart failure,
      even if they are clinically asymptomatic.

PMID- 21742100
TI  - Resting cardiac energy metabolism is inversely associated with heart rate in
      healthy young adult men.
AB  - BACKGROUND: 31-Phosphorus-magnetic resonance spectroscopy may provide
      pathophysiological insights into the high-energy phosphate metabolism of the
      myocardium as measured by phosphocreatine to adenosine triphosphate (PCr/ATP)
      ratio. Aim of the present study was to determine in vivo the relation between
      cardiac PCr/ATP ratio and heart rate in normal male subjects. METHODS: One
      hundred twelve apparently healthy, young male individuals (age 34 +/- 10 years)
      were prospectively evaluated. They underwent cardiac cine magnetic resonance
      imaging to assess left ventricular (LV) function and morphology and 3D-ISIS (31)P
      magnetic resonance spectroscopy of the LV to assess the PCr/ATP ratio (a
      recognized in vivo marker of myocardial energy metabolism). Data were analyzed
      after segregation by tertiles of the resting PCr/ATP ratio. RESULTS: A
      significant inverse association between PCr/ATP ratios and resting heart rate was
      observed (Spearman rho: r=-0.37; P < .0001). PCr/ATP ratios were also inversely
      associated with body mass index, diastolic blood pressure, wall mass and with
      insulin resistance, but in multiple regression analysis heart rate was found to
      be independently related to PCr/ATP. CONCLUSIONS: The present study shows that
      resting heart rate is proportionally lower across tertiles of increasing PCr/ATP
      ratio of the LV in apparently healthy young male individuals, supporting the
      hypothesis that heart rate is a major determinant of cardiac energy stores. These
      findings may explain the prognostic role of heart rate in the general population
      as evidenced by previous large epidemiological studies.

PMID- 21742101
TI  - The Romanian Acute Heart Failure Syndromes (RO-AHFS) registry.
AB  - AIMS: The objective of the RO-AHFS registry was to evaluate the epidemiology,
      clinical presentation, inpatient management, and hospital course in a population
      hospitalized for acute heart failure syndromes. METHODS: During a 12-month
      period, 13 Romanian medical centers enrolled all consecutive patients
      hospitalized with a primary diagnosis of AHFS. Patients were classified into the
      following 5 clinical profiles at admission: acute decompensated heart failure,
      cardiogenic shock, pulmonary edema, right heart failure, and hypertensive heart
      failure. Statistical significance was assessed using Fisher exact test or the
      chi(2) test for categorical variables and a 1-way analysis of variance for
      continuous variables. Independent predictors of in-hospital all-cause mortality
      (ACM) were identified using a multivariate logistic regression model. RESULTS: A
      total of 3,224 consecutive patients hospitalized with AHFS were enrolled. The
      cohort had a mean age of 69.2 +/- 11.8 years and 56% were men. The mean left
      ventricular ejection fraction was 37.7% +/- 12.5%. The percentage of patients
      treated with evidence-based heart failure therapies increased from admission to
      discharge, but even at discharge, only 56%, 66%, and 54% of patients were on a
      beta-blocker, an angiotensin-converting enzyme inhibitors or an angiotensin
      receptor blocker, and a mineralocorticoid receptor antagonist, respectively. In
      hospital ACM was 7.7% with substantial variation between sites (4.1%-11.0%).
      Increasing age, inotrope therapy, the presence of life-threatening ventricular
      arrhythmias, and elevated baseline blood urea nitrogen were all found to be
      independent risk factors for in-hospital ACM, whereas elevated systolic blood
      pressure and baseline treatment with a beta-blocker had a protective effect.
      CONCLUSIONS: The RO-AHFS study found substantial variation both among sites and
      between Romania and other European countries. National and regional registries
      have important clinical implications for patient care and the design and conduct
      of global clinical trials.

PMID- 21742102
TI  - Atrial fibrillation and mortality in African American patients with heart
      failure: results from the African American Heart Failure Trial (A-HeFT).
AB  - BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure
      (HF) and portends a worsened prognosis. Because of the low enrollment of African
      American subjects (AAs) in randomized HF trials, there are little data on AF in
      AAs with HF. This post hoc analysis reviews characteristics and outcomes of AA
      patients with AF in A-HeFT. METHODS AND RESULTS: A total of 1,050 AA patients
      with New York Heart Association class III/IV systolic HF, well treated with
      neurohormonal blockade (87% beta-blockers, 93% angiotensin-converting enzyme
      inhibitor and/or angiotensin receptor blocker), were randomized to an added fixed
      dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo. Atrial
      fibrillation was confirmed in 174 (16.6%) patients at baseline and in an
      additional 9 patients who developed AF during the study, for a final cohort of
      183 (17.4%). Comparison of patients with AF versus no AF revealed the following:
      mean age 61 +/- 12 versus 56 +/- 13 years (P < .001), systolic blood pressure
      (BP) 124 +/- 18 versus 127 +/- 18 mm Hg (P = .044), diastolic BP 74 +/- 11 versus
      77 +/- 10 mm Hg (P = .002), creatinine level 1.4 +/- 0.5 versus 1.2 +/- 0.5 mg/dL
      (P < .001), and brain natriuretic peptide 431 +/- 443 versus 283 +/- 396 pg/mL (P
      < .001). No significant difference was observed in ejection fraction, left
      ventricular end-diastolic diameter, or quality-of-life scores. However, AF
      increased the risk of mortality significantly among AA patients (P = .018), and
      the use of FDC I/H reduced the risk of mortality in patients with AF (HR 0.21, P
      = .002). CONCLUSION: African Americans with HF and AF (vs no AF) were older, had
      lower BP, and had higher creatinine and brain natriuretic peptide levels.
      Mortality and morbidity were worse when AF was present, and these data suggest
      that there may be an enhanced survival benefit with the use of FDC I/H in AA
      patients with HF and AF.

PMID- 21742103
TI  - The effect of ticagrelor versus clopidogrel on high on-treatment platelet
      reactivity: combined analysis of the ONSET/OFFSET and RESPOND studies.
AB  - OBJECTIVES: The objective of the study was to determine the prevalence of high on
      treatment platelet reactivity (HPR) in coronary artery disease patients enrolled
      in the ONSET/OFFSET and RESPOND studies. BACKGROUND: HPR has been linked to the
      occurrence of adverse events after stenting in patients treated with clopidogrel
      (C) and aspirin. Prevalence of HPR after treatment with ticagrelor (T), a
      reversible oral P2Y(12) receptor antagonist developed to overcome the limitations
      of C, is unknown. METHODS: Patients were treated with T (n = 106) or C (n = 103)
      on top of aspirin therapy. HPR was defined by published cutoff points associated
      with post-percutaneous coronary intervention ischemic risk: >59% 20 MUM adenosine
      diphosphate-induced aggregation (light transmittance aggregometry), >235 P2Y12
      reaction unit by VerifyNow P2Y(12) assay (VerifyNow, San Diego, CA), and >50%
      platelet reactivity index by vasodilator-stimulated phosphoprotein
      phosphorylation assay (VASP-P). Proportion differences for T versus C were
      analyzed by chi(2) test for each time point. Correlations (R) were analyzed by
      the Pearson method. RESULTS: Ticagrelor was associated with a significantly lower
      prevalence of HPR (0%-8%) compared with C (21%-81%) at 2, 4, 8, and 24 hours and
      >=2 weeks postdosing (P < .0001, for all assays). The R values between light
      transmittance aggregometry and VerifyNow/VASP-P were all >=0.43, P < .0001.
      CONCLUSIONS: The above data represent the largest serial pharmacodynamic
      evaluation of the comparative effects of T versus C. Ticagrelor was rapidly and
      consistently associated with a very low prevalence of HPR compared with C, as
      determined by multiple established methods to measure platelet reactivity. These
      results provide a mechanism for the lower ischemic event rate associated with T
      therapy reported in the PLATO trial.

PMID- 21742104
TI  - Polymorphisms associated with in vitro aspirin resistance are not associated with
      clinical outcomes in patients with coronary artery disease who report regular
      aspirin use.
AB  - BACKGROUND: We hypothesized that single-nucleotide polymorphisms (SNPs)
      associated with heightened in vitro platelet function during aspirin exposure
      (which we define as "laboratory aspirin resistance") would be associated with
      greater risk for death, myocardial infarction (MI) or stroke among patients with
      coronary artery disease regularly using aspirin. METHODS: Duke Databank for
      Cardiovascular Disease patients with (n = 3,449, CATHeterization GENetics cohort)
      or without (n = 11,754, nongenetic cohort) banked DNA with >=1 coronary stenosis
      >75% were followed up at 6 months, then annually for death, MI, or stroke
      occurring during periods of reported aspirin use. We evaluated associations of
      candidate SNPs from GNB3, PEAR1, ITGB3, VAV3, ITGA2, GPVI, PTGS1, F2R, THBS1,
      A2AR, and GP1BA with events during follow-up using Cox proportional hazards
      modeling adjusted for clinical characteristics associated with outcomes in the
      nongenetic cohort. RESULTS: Over a median of 3.5 years, 2,762 (24%) nongenetic
      cohort patients and 648 (19%) CATHeterization GENetics cohort patients had the
      composite outcome during reported aspirin use. No candidate SNPs were
      significantly associated with death, MI, or stroke in either univariable or
      multivariable analyses. A prospective analysis demonstrated 80% to 88% power to
      detect a hazard ratio of >=1.3 for minor allele carriers. CONCLUSION: Patients
      with angiographically significant coronary artery disease regularly using aspirin
      and carrying SNPs associated with laboratory aspirin resistance were not at
      higher risk for death, MI, or stroke. Using these SNPs to guide more aggressive
      antiplatelet therapy is not justified by these results. Direct extrapolation from
      in vitro findings to the clinical setting should be avoided.

PMID- 21742105
TI  - Changes in reference vessel diameter in ST-segment elevation myocardial
      infarction after primary percutaneous coronary intervention: implications for
      appropriate stent sizing.
AB  - BACKGROUND: Stents may be undersized during primary percutaneous coronary
      intervention (PCI) in ST-segment elevation myocardial infarction (STEMI), leading
      to higher rates of stent thrombosis. We sought to compare the reference vessel
      diameter (RVD) of the infarct-related artery before, immediately after, and at
      late follow-up after PCI for STEMI. We further investigated whether vessels
      treated with paclitaxel-eluting (PES) or bare-metal stents (BMS) behave
      differently with respect to RVD at follow-up. METHODS: From the HORIZONS-AMI
      trial, we identified 2,974 patients (3,589 lesions) with complete quantitative
      angiographic data for stent implantation (2,233 treated with PES and 741 treated
      with BMS). RESULTS: Considering all lesions, the median RVD was 2.87 mm (25th
      75th percentile 2.54-3.22 mm) at baseline, 2.92 mm (2.58-3.28 mm) immediately
      post-PCI, and 2.88 mm (2.55-3.22 mm) after 13 months (1,197 patients; P = .001
      pre vs post, P = .06 post vs follow-up, and P = .21 pre vs follow-up). There were
      no significant differences between the RVD for PES versus BMS at any period. The
      maximal stent or balloon size was 3.00 mm (3.00-3.50 mm) for both groups. There
      were no differences in RVD at baseline or post-PCI between patients with and
      without stent thrombosis. CONCLUSIONS: Reference vessel diameter does not change
      substantially from baseline to follow-up, irrespective of stent type. Stent
      diameter was appropriate for vessel size. The RVD of patients with and without
      stent thrombosis was similar at baseline and post-PCI. Thus, the high rates of
      stent thrombosis after primary PCI for STEMI cannot be attributed to stent
      undersizing.

PMID- 21742106
TI  - Association of initial thrombolysis in myocardial infarction flow grade with
      mortality among patients with ST-segment elevation myocardial infarction
      undergoing primary percutaneous coronary intervention: a National Registry of
      Myocardial Infarction-5 (NRMI-5) analysis.
AB  - BACKGROUND: Initial epicardial coronary flow, as assessed by the Thrombolysis in
      Myocardial Infarction flow grade (TFG), prior to primary percutaneous coronary
      intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) has
      been associated with short- and long-term mortality in randomized clinical
      trials. This study was designed to determine the relationship between initial TFG
      and mortality in a large, heterogeneous, real-world population of STEMI patients
      undergoing pPCI. METHODS: The relationship between pre-pPCI TFG among patients
      undergoing pPCI and in-hospital mortality was evaluated among STEMI patients from
      2004 to 2006 in the National Registry of Myocardial Infarction. RESULTS: Of 8,337
      STEMI patients, 6,595 (79.1%) had pre-pPCI TFG 0/1, 1,126 (13.5%) had pre-pPCI
      TFG 2, and 616 (7.4%) had pre-pPCI TFG 3. TFG 0/1 prior to pPCI was associated
      with 3.4% in-hospital mortality, whereas TFG 2 (2.0%) and TFG 3 (1.8%) were
      associated with significantly lower mortality (TFG 0/1 vs TFG 2, P = .013; TFG
      0/1 vs TFG 3, P = .035). TFG 0/1 prior to pPCI was also associated with a
      significant increase in the composite of death, recurrent myocardial infarction,
      heart failure, and shock (16.1%) when compared with patients presenting with TFG
      2 (11.5%; P < .001) and TFG 3 (7.6%; P < .001). The difference in this composite
      was also significant between patients presenting with TFG 2 and TFG 3 (P = .01).
      CONCLUSIONS: In a large, heterogeneous group of real-world patients presenting
      with STEMI, pre-pPCI TFG 0/1 is associated with higher in-hospital mortality and
      other major adverse cardiovascular events. These results corroborate prior to
      post hoc analyses from randomized clinical trials and support continued efforts
      aimed at safely establishing early infarct-related artery patency among patients
      with STEMI.

PMID- 21742107
TI  - Body mass index and health status in the Bypass Angioplasty Revascularization
      Investigation 2 Diabetes Trial (BARI 2D).
AB  - BACKGROUND: The longitudinal association between obesity, weight variability, and
      health status outcomes is important for patients with coronary disease and
      diabetes. METHODS: The BARI 2D was a multicenter randomized clinical trial
      designed to evaluate treatment strategies for patients with both documented
      stable ischemic heart disease and type 2 diabetes. We examined BARI 2D
      participants for 4 years to study how body mass index (BMI) was associated with
      health status outcomes. Health status was evaluated by the Duke Activity Status
      Index (DASI), RAND Energy/fatigue, Health Distress, and Self-rated Health. Body
      mass index was measured quarterly throughout follow-up years, and health status
      was assessed at each annual follow-up visit. Variation in BMI measures was
      separated into between-person and within-person change in longitudinal analysis.
      RESULTS: Higher mean BMI during follow-up years (the between-person BMI) was
      associated with poorer health status outcomes. Decreasing BMI (the within-person
      BMI change) was associated with better Self-rated health. The relationships
      between BMI variability and DASI or Energy appeared to be curvilinear and
      differed by baseline obesity status. Decreasing BMI was associated with better
      outcomes if patients were obese at baseline but was associated with poorer DASI
      and Energy outcomes if patients were nonobese at baseline. CONCLUSIONS: For
      patients with stable ischemic heart disease and diabetes, weight gain was
      associated with poorer health status outcomes, independent of obesity-related
      comorbidities. Weight reduction is associated with better functional capacity and
      perceived energy for obese patients but not for nonobese patients at baseline.

PMID- 21742108
TI  - Long-term results of atrial fibrillation ablation: the importance of all initial
      ablation failures undergoing a repeat ablation.
AB  - BACKGROUND: Ablation is more successful for patients with paroxysmal atrial
      fibrillation (AF1) than for those with persistent (AF2) or longstanding
      persistent AF (AF3). Many patients fail initial ablation and undergo repeat
      ablations. Little is known about repeat ablation procedure times, complications,
      and outcomes. METHODS: We evaluated Kaplan-Meier freedom from AF by AF type and
      sex for initial and repeat ablations and for final status of 843 patients
      undergoing 1122 ablations. We examined complications, procedure times and reasons
      why patients do not undergo repeat ablations. Cox multivariate analysis evaluated
      factors predicting ablation failure. RESULTS: Initial ablations were more
      successful in AF1 than AF2 or AF3 (P < .0001) patients. For each AF type, repeat
      ablations were more successful than initial ablations (P = .01 to <.001).
      Procedure times (139.1 +/- 49.1 vs 135.3 +/- 45.6 minutes, P = .248) and major
      complications (1.66% vs 2.87%, P = .216) were similar. Women had different
      clinical characteristics than men, similar initial and repeat ablation success
      rates but lower overall success because of fewer repeat ablations (57.8% vs
      68.2%, P = .047) due to patient choice (P = .028). Patients with either
      successful initial ablations or undergoing repeat ablations had late AF
      recurrence rates of 0% to 1.5% a year. Age (P = .012), larger left atria (P =
      .002), female sex (P = .001), AF2 (P < .0001), AF3 (P = .003), and coronary
      disease (P = .003) predicted failure. CONCLUSIONS: Repeat ablations are more
      successful than initial ablations, have similar procedure times and complication
      rates, help determine final success rates, and may explain sex difference in
      success rates. For the best outcomes, patients should assume that a repeat
      ablation may be required to eliminate AF.

PMID- 21742109
TI  - Analytica Chimica Acta. 6th International Symposium on Hormone and Veterinary
      Drug Residue Analysis Gent, Belgium, 1-4 June 2010--HVDA-2010. Preface.

PMID- 21742110
TI  - Development, validation and data quality assurance of screening methods: a case
      study.
AB  - Despite the growing importance of qualitative screening tests in routine
      laboratories involved in the EU official control, their validation is not as
      deeply explained in Commission Decision 2002/657/EC as the validation of
      quantitative confirmatory methods. At the same time, the issue of quality
      assurance of screening assays defining internal quality control (IQC) procedures
      as required by accreditation bodies is undoubtedly less developed in this
      analytical field. As an example the present study describes the development, the
      validation and the IQC implemented for a commercial enzyme linked immunosorbent
      assay (ELISA) able to detect 17-alpha-19-nortestosterone (alpha-NT) and 17-beta
      19-nortestosterone (beta-NT) isomers in bullock urine. In order to select a
      suitable sample treatment, two SPE purification protocols were preliminary
      compared. The chosen method was therefore fully validated determining the
      mandatory parameters required by Commission Decision 2002/657/EC: specificity,
      detection capability and robustness. An in-depth discussion was carried out
      illustrating the possible validation approaches and their implications especially
      in the assessment of the key performance characteristic: detection capability.
      Finally, the control charts implemented for continuous method verification during
      analyses of real samples were reported.

PMID- 21742111
TI  - Validation study on avermectine residues in foodstuffs.
AB  - Avermectines are antiparasitic agents widely used as veterinary drugs for food
      producing animals. The European Community, due to their side effects, limited the
      use of these molecules establishing maximum residue limits (MRLs) in some foods.
      A validated qualitative and quantitative high performance liquid chromatography
      method with fluorescence detection (HPLC-FL) is presented for the simultaneous
      determination of ivermectin (IVM), abemectin (ABA), moxidectin (MOX),
      eprinomectin (EPR), doramectin (DOR) and emamectin (EMA) in foodstuffs (muscle,
      eggs and milk). Samples were extracted with acetonitrile, purified with liquid
      liquid extraction (LLE), and analysed by HLPC-FL previous derivatization with
      trifluoroacetic anhydride (TFAA) in presence of 1-methyl-imidazole (MI) and
      acetic acid. To date, the presented method is the first validated for the matrix
      eggs, and in accordance with the requirements set by Commission Decision
      2002/657/EC. Recoveries of the methods, calculated spiking the samples in the
      range 5.0-100.0 MUg kg(-1), were 64-83% for muscle, 65-89% for milk and 63-84%
      for eggs. The precision (CV) ranged between 9.2 and 17.1% for muscle, 9.9 and
      16.6% for milk and from 9.4 to 17.4% for eggs. Linearity for the six analytes was
      calculated from 5.0 to 200.0 MUg kg(-1). The main advantages of the presented
      method are its rapidity, the specificity, the good precision and recovery that
      make it very suitable to the detection and determination of avermectines.

PMID- 21742112
TI  - Metabolomic approach based on liquid chromatography coupled to high resolution
      mass spectrometry to screen for the illegal use of estradiol and progesterone in
      cattle.
AB  - Administration of hormonal compounds as growth promoters in livestock farming was
      banned by Council Directive 93/22/EC, however, this kind of substances are
      sometimes reported within the framework of European monitoring residue plans.
      Various analytical methods have been previously developed to screen for their
      misuse, and they are now especially efficient for monitoring the illegal
      administration of synthetic and semi-synthetic hormones. Nevertheless, proving an
      exogenous administration of hormones from natural origin (i.e. estradiol-17beta
      or progesterone) still remains a challenging task for European authorities. As a
      result of their origin, these target compounds are indeed always present in the
      analytical matrix, and because the concentration levels of natural steroids are
      extremely variable from one animal to another, the establishment of reference
      thresholds appears very difficult. During this preliminary study, metabolomic
      data was acquired on a high performance liquid chromatography system coupled to
      high resolution mass spectrometer (HPLC-LTQ-Orbitrap). Serum samples were
      collected from dairy cows treated or not with sex steroid hormones commonly
      employed in animal husbandry: estradiol-17beta (or its ester estradiol benzoate)
      and progesterone. After appropriate data processing and multivariate statistical
      analyses (OPLS-DA), it was possible to highlight significant metabolic
      modifications in serum consecutively to the administration of estradiol and/or
      progesterone. Those differences were used to build predictive models able to
      suspect illegal administration of these hormones in cattle. Potential biomarker
      candidates of estradiol and/or progesterone were pointed out, that remains to be
      structurally elucidated.

PMID- 21742113
TI  - Determination of eleven coccidiostats in animal feed by liquid chromatography
      tandem mass spectrometry at cross contamination levels.
AB  - A confirmatory multi-residue method has been developed to allow for the
      detection, confirmation and quantification of eleven coccidiostats in animal feed
      by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method can be
      used to determine halofuginone, robenidine, nicarbazin, diclazuril, decoquinate,
      semduramicin, lasalocid, monensin, salinomycin, narasin, maduramicin at levels
      relating to unavoidable carry over as stated in Regulation 2009/8/EC. Feed
      samples are extracted with water and acetonitrile with the addition of anhydrous
      magnesium sulphate and sodium chloride. The extract then undergoes a freezing out
      step before being diluted and injected onto the LC-MS/MS system. The LC-MS/MS
      system is run in MRM mode with both positive and negative electrospray ionisation
      and can confirm all eleven analytes in a run time of 19 min. The sensitivity of
      the method allows quantification and confirmation for all coccidiostats at a 0.5%
      carry over level. The method was validated over three days in accordance with of
      European legislation; Commission Decision 2002/657/EC. Validation criteria of
      accuracy, precision, decision limit (CCalpha), and detection capability (CCbeta)
      along with measurement uncertainty are calculated for all analytes. The method
      was then successfully used to analyse a number of feed samples that contained
      various coccidiostat substances.

PMID- 21742114
TI  - The application of reporter gene assays for the detection of endocrine disruptors
      in sport supplements.
AB  - The increasing availability and use of sports supplements is of concern as
      highlighted by a number of studies reporting endocrine disruptor contamination in
      such products. The health food supplement market, including sport supplements, is
      growing across the Developed World. Therefore, the need to ensure the quality and
      safety of sport supplements for the consumer is essential. The development and
      validation of two reporter gene assays coupled with solid phase sample
      preparation enabling the detection of estrogenic and androgenic constituents in
      sport supplements is reported. Both assays were shown to be of high sensitivity
      with the estrogen and androgen reporter gene assays having an EC(50) of 0.01 ng
      mL(-1) and 0.16 ng mL(-1) respectively. The developed assays were applied in a
      survey of 63 sport supplements samples obtained across the Island of Ireland with
      an additional seven reference samples previously investigated using LC-MS/MS.
      Androgen and estrogen bio-activity was found in 71% of the investigated samples.
      Bio-activity profiling was further broken down into agonists, partial agonists
      and antagonists. Supplements (13) with the strongest estrogenic bio-activity were
      chosen for further investigation. LC-MS/MS analysis of these samples determined
      the presence of phytoestrogens in seven of them. Supplements (38) with androgen
      bio-activity were also selected for further investigation. Androgen agonist bio
      activity was detected in 12 supplements, antagonistic bio-activity was detected
      in 16 and partial antagonistic bio-activity was detected in 10. A further group
      of supplements (7) did not present androgenic bio-activity when tested alone but
      enhanced the androgenic agonist bio-activity of dihydrotestosterone when
      combined. The developed assays offer advantages in detection of known, unknown
      and low-level mixtures of endocrine disruptors over existing analytical screening
      techniques. For the detection and identification of constituent hormonally active
      compounds the combination of biological and physio-chemical techniques is
      optimal.

PMID- 21742115
TI  - Detection of benzimidazole carbamates and amino metabolites in liver by surface
      plasmon resonance-biosensor.
AB  - Two surface plasmon resonance (SPR) biosensor screening assays were developed and
      validated to detect 11 benzimidazole carbamate (BZT) and four amino-benzimidazole
      veterinary drug residues in liver tissue. The assays used polyclonal antibodies,
      raised in sheep, to detect BZTs and amino-benzimidazoles. A modified Quick, Easy,
      Cheap, Effective, Rugged and Safe (QuEChERS) extraction method was developed to
      isolate benzimidazole carbamate residues. Liver samples were extracted using an
      acetonitrile extraction method. BZTs were purified by dispersive solid phase
      extraction (d-SPE) using C(18) sorbent. Residues of amino-benzimidazoles were
      effectively cleaned-up using a simple cyclohexane defatting step. The assays were
      validated in accordance with the performance criteria described in 2002/657/EC.
      The BZT assay limit of detection was calculated to be 32 MUg kg(-1), the
      detection capability (CCbeta) was determined to be 50 MUg kg(-1) and the mean
      recovery of analytes was in the range 77-132%. The amino-benzimidazole assay
      limit of detection was determined to be 41 MUg kg(-1), the CCbeta was determined
      to be 75 MUg kg(-1) and analyte recovery was in the range 103-116%. Biosensor
      assay performance was tested by analysing liver tissue from animals treated with
      benzimidazole drugs and comparing the results with an ultra high performance
      liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) confirmatory method.
      All non-compliant samples were identified using the biosensor assays.

PMID- 21742116
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      method for the simultaneous determination of nine corticosteroid residues in
      bovine liver samples.
AB  - A liquid chromatography tandem mass spectrometry (LC-MS/MS) confirmatory method
      for the simultaneous determination of nine corticosteroids in liver, including
      the four MRL compounds listed in Council Regulation 37/2010, was developed. After
      an enzymatic deconjugation and a solvent extraction of the liver tissue, the
      resulting solution was cleaned up through an SPE Oasis HLB cartridge. The
      analytes were then detected by liquid chromatography-negative-ion electrospray
      tandem mass spectrometry, using deuterium-labelled internal standards. The
      procedure was validated as a quantitative confirmatory method according to the
      Commission Decision 2002/657/EC criteria. The results showed that the method was
      suitable for statutory residue testing regarding the following performance
      characteristics: instrumental linearity, specificity, precision (repeatability
      and intra-laboratory reproducibility), recovery, decision limit (CCalpha),
      detection capability (CCbeta) and ruggedness. All the corticosteroids can be
      detected at a concentration around 1 MUg kg(-1); the recoveries were above 62%
      for all the analytes. Repeatability and reproducibility (within-laboratory
      reproducibility) for all the analytes were below 7.65% and 15.5%, respectively.

PMID- 21742117
TI  - Preparation and characterisation of in-house reference material of tylosin in
      honey and results of a proficiency test.
AB  - The analysis of incurred material from animals treated with pharmacologically
      active substances is an efficient way to check the accuracy of a method. Tylosin
      A was chosen for the preparation of that material because it is highly effective
      in controlling active infections of American Foulbrood (AFB), a global threat to
      apiculture, but residues in honey are not allowed according to European
      legislation. For this reason an in-house reference material of honey containing
      the macrolide tylosin A and its degradation product desmycosin (tylosin B) was
      prepared. After the treatment of a beehive with the appropriate macrolide tylosin
      A, the honey samples were collected. The incurred honey material was diluted by
      mixing with blank honey. Concentrations of 25.81 MUg kg(-1) for tylosin A and of
      19.28 MUg kg(-1) for its degradation product desmycosin (tylosin B) were reached.
      The homogeneity was checked by analysing 12 bottles in duplicate. The stability
      was tested at different defined temperatures and storage conditions. The
      reference material described above was homogeneous and stable. Samples of this in
      house reference material were used for the realisation of a proficiency test with
      international participation. All participants accomplished satisfying results
      with the exception of one laboratory.

PMID- 21742118
TI  - Feasibility of desorption electrospray ionization mass spectrometry for rapid
      screening of anabolic steroid esters in hair.
AB  - Hormone and veterinary drug screening and forensics can benefit from the recent
      developments in desorption electrospray ionization (DESI) mass spectrometry (MS).
      In this work the feasibility of DESI application for the rapid screening of
      intact esters of anabolic steroids in bovine hair has been studied. Using a
      linear ion trap both full scan and data-dependent collision induced dissociation
      MS(n) spectra were acquired in minutes for testosterone cypionate, testosterone
      decanoate and estradiol benzoate standard solutions deposited on a glass or PTFE
      surface. However direct analysis of incurred hair failed due to inefficient
      desorption ionization and the minute quantities of steroid esters present.
      Therefore a simplified ultrasonic liquid extraction procedure was developed,
      allowing rapid DESI analysis of a few microliters of the concentrate and a total
      analysis time of 2-4h per batch instead of 3 days. The potential of this DESI
      approach is clearly demonstrated by MS(3) data from hair samples incurred with
      high levels (300-800 MUg kg(-1)) of steroid esters, levels which do occur in
      samples from controlled- and illegally treated animals. For much lower levels
      state-of-the-art ultra high performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS) screening methods remain the method of choice and might
      benefit from the proposed simplified extraction as well.

PMID- 21742119
TI  - Ultra-high performance liquid chromatography-tandem mass spectrometry in high
      throughput confirmation and quantification of 34 anabolic steroids in bovine
      muscle.
AB  - An ultra-high performance liquid chromatography tandem mass spectrometry multi
      residue method for the determination of 34 anabolic steroids (10 estrogens
      including stilbenes, 14 androgens and 10 gestagens) in meat of bovine origin is
      reported. The extraction and clean-up procedure involved homogenization with
      methanol, defatting with hexane, liquid/liquid extraction with diethylether and
      finally SPE clean-up with coupled Si and NH(2) cartridges. The analytes were
      separated on a 1.9 MUm Hypersil Gold column (100*2.1 mm) and quantified on a
      triple quadrupole mass spectrometer (TSQ Vantage) operating simultaneously in
      both positive and negative atmospheric pressure chemical ionisation (APCI) modes.
      This analytical procedure was subsequently validated according to EU criteria (CD
      2002/657/EC), resulting in decision limits and detection capabilities ranging
      between 0.04 and 0.88 MUg kg(-1) and 0.12 and 1.9 MUg kg(-1), respectively. The
      method obtained for all, natural and synthetic steroids, adequate precisions and
      intra-laboratory reproducibilities (relative standard deviation below 20%), and
      the linearity ranged between 0.991 and 0.999. The performance characteristics
      fulfill the recommended concentrations fixed by the Community Reference
      Laboratories. The developed analysis is sensitive, and robust and therefore
      useful for confirmation and quantification of anabolic steroids for research
      purposes and residue control programs.

PMID- 21742120
TI  - Discrimination of eight chloramphenicol isomers by liquid chromatography tandem
      mass spectrometry in order to investigate the natural occurrence of
      chloramphenicol.
AB  - This paper describes the discrimination of eight different isomers of
      chloramphenicol (CAP), an antibiotic banned for use in food producing animals, by
      reversed phase and chiral liquid chromatography in combination with tandem mass
      spectrometric detection. Previously, by liquid chromatography coupled to tandem
      mass spectrometry (LC-MS/MS) the presence of CAP was confirmed in some grass and
      herb samples collected on Mongolian pastures up to concentrations of 450 MUg kg(
      1). It was not possible to establish the cause of CAP residues which has
      initiated research on the natural occurrence of this drug. CAP occurs in the para
      configuration and in the meta-configuration and contains two chiral centers thus
      eight different isomeric configurations exist, namely four (RR, SS, RS, SR) meta
      stereoisomers and four para-stereoisomers. It is known that only RR-p-CAP has
      antimicrobial properties. To find out if the CAP detected in the plant material
      samples is the active configuration, a high resolution reversed phase LC-MS/MS
      system was tested for its ability to separate the different isomers. This system
      proved to be able to discriminate between some isomers, but not between RR-p-CAP
      and SS-p-CAP, also called dextramycin. Despite a detailed elucidation of the
      product ions and the fragmentation patterns of all isomers, MS/MS did not add
      sufficient specificity for full discrimination of the isomers. Therefore a chiral
      liquid chromatographic separation with MS/MS detection that is able to
      distinguish all isomers was developed and finally the isomeric ratio of non
      compliant plant material samples and some CAP formulations was determined using
      this system. This showed that Mongolian grass and herb samples only contain the
      biological active isomer of CAP as do the obtained formulations. Therefore the
      CAP present in the plant material might origin from the production by soil
      organisms or from a manufactured source.

PMID- 21742121
TI  - Development of an improved high resolution mass spectrometry based multi-residue
      method for veterinary drugs in various food matrices.
AB  - Multi-residue methods for veterinary drugs or pesticides in food are increasingly
      often based on ultra performance liquid chromatography (UPLC) coupled to high
      resolution mass spectrometry (HRMS). Previous available time of flight (TOF)
      technologies, showing resolutions up to 15,000 full width at half maximum (FWHM),
      were not sufficiently selective for monitoring low residue concentrations in
      difficult matrices (e.g. hormones in tissue or antibiotics in honey). The
      approach proposed in this paper is based on a single stage Orbitrap mass
      spectrometer operated at 50,000 FWHM. Extracts (liver and kidney) which were
      produced according to a validated multi-residue method (time of flight detection
      based) could not be analyzed by Orbitrap because of extensive signal suppression.
      This required the improvement of established extraction and clean-up procedures.
      The introduced, more extensive deproteinzation steps and dedicated instrumental
      settings successfully eliminated these detrimental suppression effects. The
      reported method, covering more than 100 different veterinary dugs, was validated
      according to the EU Commission Decision 2002/657/EEC. Validated matrices include
      muscle, kidney, liver, fish and honey. Significantly better performance
      parameters (e.g. linearity, reproducibility and detection limits) were obtained
      when comparing the new method with the older, TOF based method. These
      improvements are attributed to the higher resolution (50,000 versus 12,000 FWHM)
      and the superior mass stability of the of the Orbitrap over the previously
      utilized TOF instrument.

PMID- 21742122
TI  - Effects of low-dose dexamethasone and prednisolone long term administration in
      beef calf: chemical and morphological investigation.
AB  - An analytical, pharmacokinetic and histopathologic investigation was conducted by
      two experimental trials on beef cattle in order to determine fate and effects of
      dexamethasone and prednisolone, administered to distinct cattle groups at low
      dosage for long periods of time. In trial 1, eighteen Charolaise beef cattle,
      male, 17-22-months-old, were divided in three groups: to group A (n=6)
      dexamethasone-21-sodium-phosphate 0.7 mg day(-1) per os for 40 days was
      administered; group B (n=6) was orally treated with prednisolone 15 mg day(-1)
      for 30 days, while group C (n=6) served as negative control. Urine was collected
      at days 0, 7, 15, 25 and 47 from groups A and C, and at days 0, 8, 18 and 42 from
      group B. In trial 2, sixteen Friesian cattle, male, 10-17-months-old, were
      randomly divided into two groups: group D (n=8) was administered prednisolone 30
      mg day(-1) per os for 35 days, while group K (n=8) served as control. In both
      trials, the animals were slaughtered after a 6-days drug withdrawal and thymus
      and livers were collected and properly stored until the analysis was performed.
      Quantitative determinations of dexamethasone, prednisolone and its main
      metabolite, prednisone, in urine and liver samples were conducted by HPLC-MS/MS,
      after the analytical procedure was optimized and fully validated. The method
      validation included the assessment of specificity, linearity, precision,
      trueness, robustness, CC(alpha) and CC(beta) values. By a morphological point of
      view, severe atrophy of thymus parenchyma was observed in group A, together with
      a significant (P<0.005) reduction of the mean thymus weight (217+/-94 g), while
      group B (646+/-215 g) presented normal thymus features and weights (group C,
      415+/-116 g). Accordingly, no differences were found in trial 2 for groups D
      (727+/-275g) and K (642+/-173 g). Average dexamethasone concentrations in group A
      urine samples ranged from 1.4 to 3.0 MUg L(-1) during the treatment, while no
      residue was detected in the urine samples collected 6-7 days after the end of the
      treatment. Low amounts of dexamethasone (<1 MUg L(-1)) were detected in liver
      samples of group A. All average prednisolone concentrations in group B urine
      samples (sum of conjugate and free form) turned out to be below 1.0 MUg L(-1)
      during the treatment, despite the much higher concentration administered (15-30
      mg day(-1)) with respect to dexamethasone in group A (0.7 mg day(-1)). No
      prednisolone residues were found in the urine and liver samples taken at the
      slaughterhouse. The absence of any prednisolone residue in the urine samples of
      control group animals supports the theory that the origin of this molecule is
      fundamentally exogenous, at least for this cattle category maintained under
      unstressing conditions. Remarkable findings are represented by the absence of
      thymus atrophy in the prednisolone treated animals and the extremely low residue
      concentrations found in urine during the treatment. Both findings reveal that the
      detection of illegal growth-promoting treatments with this drug is difficult.

PMID- 21742123
TI  - Targeted phase II metabolites profiling as new screening strategy to investigate
      natural steroid abuse in animal breeding.
AB  - The use of steroid hormones as growth promoters in cattle is banned within the
      European Union since 1988 but can still be fraudulently employed in animal
      breeding farms for anabolic purposes. While efficient targeted confirmatory
      methods have been implemented in control laboratories for many years, fast and
      reliable screening methods are still required, especially in the case of natural
      hormones abuse, but more globally for new "fishing" strategies allowing to reveal
      the use of even unknown anabolic agents. The development of focused profiling or
      untargeted metabolomic approaches is thus emerging in this context. The present
      study was a focused profiling study using steroids phase II metabolites, with the
      aim to get a better understanding of the steroid metabolism disruptions after
      exogenous administration of androstenedione and finally reveal potential
      biomarkers signing its administration. A sample preparation procedure was first
      developed, based on a separation of 31 glucuronide and sulphate conjugate
      compounds using an anion exchange SPE system. Each fraction was then analysed by
      UPLC-MS/MS in MRM mode showing a rapid (between 4h and 4 days after treatment)
      and huge excretion of several direct metabolites of androstenedione such as
      etiocholanolone-glucuronide or epiandrosterone-sulphate.

PMID- 21742124
TI  - Influence of natural organic matter on the screening of pharmaceuticals in water
      by using liquid chromatography with full scan mass spectrometry.
AB  - The influence of natural organic matter on the screening of pharmaceuticals in
      water was determined by using high resolution liquid chromatography (HRLC)
      combined with full scan mass spectrometry (MS) techniques like time of flight
      (ToF) or Orbitrap MS. Water samples containing different amount of natural
      organic matter (NOM) and residues of a set of 11 pharmaceuticals were analyzed by
      using Exactive OrbitrapTM LC-MS. The samples were screened for residues of
      pharmaceuticals belonging to different classes like benzimidazoles, macrolides,
      penicillins, quinolones, sulfonamides, tetracyclines, tranquillizers, non
      steroidal anti-inflammatory drugs (NSAIDs), anti-epileptics and lipid regulators.
      The method characteristics were established over a concentration range of 0.1-500
      MUg L(-1). The 11 pharmaceuticals were added to two effluent and two influent
      water samples. The NOM concentration within the samples ranged from 2 to 8 mg L(
      1) of dissolved organic carbon. The HRLC-Exactive OrbitrapTM LC-MS system was set
      at a resolution of 50,000 (FWHM) and this selection was found sufficient for the
      detection of the list of pharmaceuticals. With this resolution setting, accurate
      mass measurements with errors below 2 ppm were found, despite of the NOM
      concentration of the different types of water samples. The linearities were
      acceptable with correlation coefficients greater than 0.95 for 30 of the 51
      measured linearities. The limit of detection varies between 0.1 MUg L(-1)and 100
      MUg L(-1). It was demonstrated that sensitivity could be affected by matrix
      constituents in both directions of signal reduction or enhancement. Finally it
      was concluded that with direct shoot method used (no sample pretreatment) all
      compounds, were detected but LODs depend on matrix-analyte-concentration
      combination. No direct relation was observed between NOM concentration and method
      characteristics. For accurate quantification the use of internal standards and/or
      sample clean-up is necessary. The direct shoot method is only applicable for
      qualitative screening purposes. The use of full scan MS makes it possible to
      search for unknown contaminants. With the use of adequate software and a database
      containing more than 50,000 entries a tool is available to search for unknowns.

PMID- 21742125
TI  - Use of benchtop exactive high resolution and high mass accuracy orbitrap mass
      spectrometer for screening in horse doping control.
AB  - Liquid chromatography-mass spectrometry (LC-MS) has been widely used in doping
      control laboratories over the last two decades. Currently, simple quadrupole,
      triple quadrupole and ion trap are the most commonly employed analyzers in
      toxicological analysis. Nevertheless, the main lack of these technologies is the
      restricted number of target compounds simultaneously screened without loss of
      sensitivity. In this article we present an innovative screening approach
      routinely applied in the French horse doping control laboratory based on high
      resolution (50000) and high mass accuracy (<5 ppm) in full scan MS mode for more
      than 235 target analytes screened from an initial volume of 5 mL of urine. The
      sample preparation was classically founded on solid phase extraction by means of
      reverse phase C18 cartridges. LC-MS analyses were carried out on a Shimadzu
      binary HPLC pumps linked to a C18 Sunfire column associated with the high
      resolution exactive benchtop orbitrap mass spectrometer. This screening was
      performed alternatively in positive-negative ionization mode during the same run.
      Thus, the identification of compounds of interest was made using their exact mass
      in positive-negative ionization mode at their expected retention time. All data
      obtained were processed by ToxID software (ThermoFisherScientific) which is able
      to identify a molecule by theoretical mass and retention time. In order to
      illustrate this innovative technology applied in our laboratory, sample
      preparation, validation data performed on 20 target compounds from 16 different
      horse urine samples, chromatograms and spectra will be discussed in this paper.

PMID- 21742126
TI  - Determination of MRL regulated corticosteroids in liver from various species
      using ultra high performance liquid chromatography-tandem mass spectrometry
      (UHPLC).
AB  - Dexamethasone, betamethasone, prednisolone and methylprednisolone are
      corticosteroids widely used in animal husbandry. These compounds are licensed for
      therapy in veterinary practices while their use for growth promoting practices,
      mainly in combination with other growth promoters, is prohibited within the
      European Union. In order to protect the consumer, maximum residue limits (MRLs)
      have been set by the European Community in liver to 2.0 MUg kg(-1) (dexamethasone
      and betamethasone) and 10.0 MUg kg(-1) (prednisolone and methylprednisolone) for
      different species. The major challenges in the analysis of dexamethasone and
      betamethasone consist in performing an efficient separation of both isomers and
      in detecting and identifying all the molecules according to the regulatory
      requirements fixed in Commission Decision 2002/657/EC. In this context, an UHPLC
      MS/MS method with a short runtime (7 min) and using the SRM acquisition mode was
      developed and validated. An efficient selectivity of the sample preparation
      combined with a high sensitivity of the measurement system allowed identifying
      and quantifying the four corticosteroids of interest in this complex biological
      matrix. Signals obtained were found very repeatable, even at very low
      concentration levels with an unambiguous identification of the compounds. The
      performance limits of the method have been validated according to the regulatory
      requirements and the method has been successfully applied to the confirmation of
      incurred liver samples.

PMID- 21742127
TI  - Assessment of two complementary liquid chromatography coupled to high resolution
      mass spectrometry metabolomics strategies for the screening of anabolic steroid
      treatment in calves.
AB  - Anabolic steroids are banned in food producing livestock in Europe. Efficient
      methods based on mass spectrometry detection have been developed to ensure the
      control of such veterinary drug residues. Nevertheless, the use of "cocktails"
      composed of mixtures of low amounts of several substances as well as the
      synthesis of new compounds of unknown structure prevent efficient prevention. New
      analytical tools able to detect such abuse are today mandatory. In this context,
      metabolomics may represent new emerging strategies for investigating the global
      physiological effects associated to a family of substances and therefore, to
      suspect the administration of steroids. The purpose of the present study was to
      set up, assess and compare two complementary mass spectrometry-based metabolomic
      strategies as new tools to screen for steroid abuse in cattle and demonstrate the
      feasibility of such approaches. The protocols were developed in two European
      laboratories in charge of residues analysis in the field of food safety. Apart
      from sample preparation, the global process was different in both laboratories
      from LC-HRMS fingerprinting to multivariate data analysis through data processing
      and involved both LC-Orbitrap-XCMS and UPLC-ToF-MS-MetAlign strategies. The
      reproducibility of both sample preparation and MS measurements were assessed in
      order to guarantee that any differences in the acquired fingerprints were not
      caused by analytical variability but reflect metabolome modifications upon
      steroids administration. The protocols were then applied to urine samples
      collected on a large group of animals consisting of 12 control calves and 12
      calves administrated with a mixture of 17beta-estradiol 3-benzoate and 17beta
      nandrolone laureate esters according to a protocol reflecting likely illegal
      practices. The modifications in urine profiles as indicators of steroid
      administration have been evaluated in this context and proved the suitability of
      the approach for discriminating anabolic treated animals from control ones. Such
      an approach may therefore open a new way for the screening of anabolic steroid
      administration through targeted monitoring of relevant biomarkers highlighted as
      a result of the metabolomics study.

PMID- 21742128
TI  - Liquid chromatography tandem mass spectrometry with ion trap and triple
      quadrupole analyzers for determination of thyreostatic drugs in urine and muscle
      tissue.
AB  - Liquid chromatography tandem mass spectrometry methods were developed and
      validated to screen for and confirm residues of the thyreostatic drugs: tapazole,
      thiouracil, methylthiouracil, propylthiouracil, and phenylthiouracil in bovine
      and porcine urine and muscle tissues using dimethylthiouracil as internal
      standard. Thyreostats were extracted from urine samples with diethyl ether after
      derivatisation with 3-iodobenzylbromide in basic medium (pH 8.0) and analyzed by
      gradient elution on a Nucleosil C18 column with ion trap mass spectrometry
      detection using an electrospray source and triple quadrupole MS detection with
      turbo spray source. Thyreostats were extracted from muscle tissue with methanol,
      the denaturation of matrix protein was performed and then the same steps as for
      the urine samples were carried out. The methods were validated in accordance with
      the Commission Decision 2002/657/EC. Good thyreostats recoveries were obtained
      (from 82% to 117%) as well as acceptable within-lab reproducibility. The values
      of the decision limit CCalpha and the detection capability CCbeta of five
      thyreostatic drugs are found to be below the recommended concentration set at 10
      MUg L(-1) (kg(-1)). The results of the validation demonstrate that liquid
      chromatography mass spectrometry with ion trap detection does not meet the
      criteria for confirmation for some thyreostats and therefore was applied for
      screening purpose only.

PMID- 21742129
TI  - Development and validation of a multi-residue liquid chromatography-tandem mass
      spectrometry confirmatory method for eleven coccidiostats in eggs.
AB  - A confirmatory method for the determination of residues of eleven coccidiostats
      including ionophore antibiotics: lasalocid, maduramycin, monensin, narasin,
      salinomycin, semduramycin and chemical coccidiostats: decoquinate, diclazuril,
      halofuginone, nicarbazin and robenidine in poultry eggs was developed and
      validated. The sample was extracted with acetonitrile, defatted with hexane and
      cleaned-up on a silica SPE cartridge. The analytes were identified and quantified
      by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method
      performance characteristics required by Commission Decision 2002/657/EC were
      estimated adopting a more flexible and simple validation design. In this
      alternative approach the experimental study focuses on a larger dynamic range
      with progressively increasing validation levels. Each of them presents equal
      concentrations of all the analytes. On the contrary the classical Decision plan
      investigates a restricted concentration range necessarily different for each
      analyte being determined by the individual permitted limit (0.5-1.5 times the
      permitted limit). As a consequence each validation level involves the
      simultaneous fortification with complex mixtures containing different
      concentrations of each analyte. Adopting this alternative strategy the validation
      of several substances with significantly different permitted limits is
      considerably simplified and a deeper knowledge of the method is achieved. The
      results proved that the method enables the confirmation of regulated
      coccidiostats in eggs at the levels required in the official control of residues
      (CCalpha in the range of 2.2-174 MUg kg(-1), depending on the coccidiostat). The
      repeatability (CV(r) in the range of 1.1-19%) and within-laboratory
      reproducibility (CV(Rw) in the range of 1.8-30%) are also acceptable. The
      procedure was successfully verified in the proficiency test and implemented in
      the national residue control plan.

PMID- 21742130
TI  - Screening method for the detection of a range of nitrofurans in avian eyes by
      optical biosensor.
AB  - An immunobiosensor assay was developed for the multi-residue screening of a range
      of nitrofuran compounds in avian eyes. A polyclonal antibody which binds at least
      5 of the major parent nitrofurans was raised in a rabbit after inoculation with a
      nitrofuran mimic-protein conjugate. Sample homogenates were extracted into 0.1M
      hydrochloric acid and subjected to clean-up by solid phase extraction and micro
      centrifugation prior to biosensor analysis. Validation data obtained from the
      analysis of 21 fortified samples has shown that the method has a detection
      capability (CCbeta) of less than 1 ng eye(-1) for nitrofurazone (NFZ). In
      addition, cross-reactivity data and the analysis of a smaller number of fortified
      samples have shown that the method will also detect a range of other major parent
      nitrofurans including furazolidone (FZD), furaltadone (FTD), nitrofurantoin (NFA)
      and nifursol (NFS). Intra-assay variation (n=10) was calculated at 12.9% and
      10.1% at concentrations of 1 ng eye(-1) and 2 ng eye(-1) NFZ respectively. Inter
      assay variation (n=3) was determined to be 10.8% and 4.7% at the same NFZ
      concentrations respectively. The cross-reactivity profile and validation data for
      the detection of these nitrofurans are presented together with the results
      obtained following the analysis of a small number of incurred samples using the
      developed method.

PMID- 21742131
TI  - Bioassay based screening of steroid derivatives in animal feed and supplements.
AB  - Receptor binding transcription activation bioassays are valuable tools for the
      screening of steroid hormones in animal feed and supplements. However, steroid
      derivatives often lack affinity for their cognate receptor and do not show any
      direct hormonal activity by themselves. These compounds are thus not detected by
      these kinds of bioassays and need a bioactivation step in order to become active,
      both in vivo and in vitro. In this study a comparison was made between different
      in vitro activation methods for hormone esters and hormone glycosides.
      Testosterone acetate and testosterone decanoate were chosen as model compounds
      for the hormone esters, representing the broad range of steroid esters of varying
      polarities, while genistin was used as a substitute model for the steroid
      glycosides. Concerning bioactivation of the steroids esters, the efficiency for
      alkaline hydrolysis was 90-100% and much better as compared to enzymatic
      deconjugation by esterase. As a result 1 MUg testosterone ester per gram of
      animal feed could easily be detected by a yeast androgen bioassay. When comparing
      different enzyme fractions for deglycosilation, genistin was shown to be
      deconjugated most efficiently by beta-glucuronidase/aryl sulfatase from Helix
      pomatia, resulting in a significant increase of estrogenic activity as determined
      by a yeast estrogen bioassay. In conclusion, chemical and enzymatic deconjugation
      procedures for ester and glycoside conjugates respectively, resulted in a
      significant increase in hormonal activity as shown by the bioassay readouts and
      allowed effective screening of these derivatives in animal feed and feed
      supplements.

PMID- 21742132
TI  - Development and validation of an enzyme-linked immunosorbent assay for the
      detection of circulating antibodies raised against growth hormone as a
      consequence of rbST treatment in cows.
AB  - The recombinant bovine growth hormone (rbST) is used to increase lactating
      performances of dairy cows. Administration of rbST is banned in the European
      Union; nevertheless, its use is probable. Until now, efficient analytical
      strategies to detect such practice are based on the direct detection by mass
      spectrometry of the presence of rbST in biological fluids, which suits for
      confirmatory purposes. Current screening strategies do not offer satisfactory
      performances; therefore, alternative screening strategies are required. The aim
      of the present work is to develop and validate an ELISA to measure the production
      of specific antibodies upon rbST in bovine sera. In this immunoassay, rbST is
      absorbed onto microtiter plate. After specific purification of the antibodies in
      serum, samples are analysed and the presence of antibodies anti-rbST is detected
      by Protein G peroxidase conjugate and 2-2'-azino di-ethyl benz-thiazoline-6
      sulphonic acid (ABTS). The mean reproducibility of the OD (lambda=405 nm)
      measurement was calculated with a CV of 13%. The intra- and inter-assay CVs
      ranged from 0.79% to 7.91% and from 2.69% to 20% respectively. The test presents
      cross-reaction with other growth hormones such as the recombinant equine (reST)
      and porcine (pST) (100% and 80% respectively). The specificity of the test toward
      rbST anabolic treatment was confirmed through the analysis of sera samples
      collected on animals administered with other anabolic compounds (steroids). The
      performances of the present anti-rbST ELISA proves its efficiency as a new
      screening tool to highlight illegal administration of rbST in cattle up to at
      least 3 weeks after treatment.

PMID- 21742133
TI  - Screening method for the analysis of antiviral drugs in poultry tissues using
      zwitterionic hydrophilic interaction liquid chromatography/tandem mass
      spectrometry.
AB  - A screening method for the analysis of seven anti-viral drugs in poultry tissue
      has been developed. These include anti-influenza drugs (amantadine, rimantadine,
      zanamivir and oseltamivir and its carboxylate metabolite), anti-herpes drugs
      (acyclovir and ganciclovir) and an immunomodulator (imiquimod). Poultry tissue
      was extracted in acetonitrile:water:acetic acid. After sample purification, using
      a strong cation exchange column, the eluate was split into two fractions. The
      first portion was dissolved in methanol:water and the second in
      acetonitrile:methanol:water. Both fractions were analysed on a zwitterionic
      hydrophilic interaction liquid chromatography column coupled to a triple
      quadrupole mass spectrometer. The screening method was successfully validated
      according to Commission Decision 2002/657/EC in three different laboratories with
      CCbeta concentrations of <=10 MUg kg(-1).

PMID- 21742138
TI  - Legg-Calve-Perthes disease.

PMID- 21742139
TI  - The epidemiology and etiology of Perthes disease.
AB  - The incidence of Perthes disease varies markedly both between countries and
      within countries down to a local level. The disease is more common in white than
      in Asian or black African children. The disease is associated with deprivation;
      with a steep disease gradient across social class groups. This epidemiology
      alongside the lack of concordance in twins suggests a strong environmental
      etiology, with little evidence to suggest a genetic predisposition. Children are
      frequently short, with a growth pattern described as "rostral-sparing". A
      propensity to associated congenital anomalies suggests an intrauterine cause.

PMID- 21742140
TI  - Pathophysiology, classifications, and natural history of Perthes disease.
AB  - Since the original reports of Legg-Calve-Perthes disease (LCPD), much research
      effort has been undertaken to improve understanding of this idiopathic hip
      disorder. This article focuses on the current knowledge of the pathophysiology,
      classifications, and natural history of LCPD. Although the cause of LCPD remains
      largely unknown, some insight has been gained on its pathophysiology through
      experimental studies using animal models of ischemic necrosis. The few available
      clinical studies on the natural history of LCPD suggest that femoral head
      deformity is well tolerated in short and intermediate terms, but 50% of patients
      develop disabling arthritis in the sixth decade of life.

PMID- 21742141
TI  - Imaging in Legg-Calve-Perthes disease.
AB  - Imaging in Legg-Calve-Perthes disease should help assess the severity and the
      stage of the disease, detect severe forms earlier, and provide guidance to
      therapy. However, due to the complexity of the disease, not all examinations can
      be performed at the same time with the same goals. The scope of this work is to
      provide an overview of all imaging techniques available today, and to help
      understand when to use a particular examination. Advantages and limitations of
      plain radiographs, bone scintigraphy, magnetic resonance imaging, arthrography,
      computed tomography, and ultrasonography are identified.

PMID- 21742142
TI  - Prognostic factors and outcome measures in Perthes disease.
AB  - The shape of the femoral head at the time when Perthes disease heals is the most
      important determinant of the risk for degenerative arthritis; hence, the shape of
      the femoral head and congruence of the hip are the most useful outcome measures.
      Although several prognostic factors that predict femoral head deformation may be
      identified during the course of Perthes disease, only two prognostic factors may
      be identified early enough to institute preventive intervention: femoral head
      extrusion and the age at onset of the disease. Femoral head extrusion is the only
      factor that may be influenced by treatment.

PMID- 21742143
TI  - Principles of containment treatment aimed at preventing femoral head deformation
      in Perthes disease.
AB  - The aim of treatment of Perthes in the early part of the disease is to prevent
      the femoral head from getting deformed by muscular forces and weight-bearing
      stresses transmitted across the acetabular margin. To achieve this, femoral head
      extrusion must be preempted in children who are older than 8 years at onset of
      the disease by ensuring containment as soon as the disease is diagnosed. In
      children younger than 8 years in whom femoral head extrusion occurs, containment
      must be obtained by the early stage of fragmentation.

PMID- 21742144
TI  - Containment methods for treatment of Legg-Calve-Perthes disease.
AB  - The objective of containment treatment in Perthes disease is to hold the femoral
      head in the acetabulum during the period of "biologic plasticity" while necrotic
      bone is resorbed and living bone is restored through the process of "creeping
      substitution." This article identifies the various methods of containment and the
      technical aspects of each method. Choice of method depends on the experience of
      the surgeon and the psychosocial needs of the patient and family. Failure is more
      commonly a result of inappropriate patient selection for a particular method,
      delay in management, or technical errors rather than to the method that was
      selected.

PMID- 21742145
TI  - Principles of treatment in late stages of Perthes disease.
AB  - It is of paramount importance to distinguish hips that may or may not be suitable
      for containment in the transitional stage (fragmentation to early reossification
      stage), because long-term clinical and radiological outcomes may be influenced by
      the choice of treatment. This article summarizes the definition of hinge
      abduction, pathoanatomy of hinge segment, assessment of hinge abduction,
      determination of reducible and irreducible hinge abduction, and treatment
      strategies for containable and uncontainable hips in the transitional stage.

PMID- 21742146
TI  - Valgus osteotomy for hinge abduction.
AB  - Failure of the enlarged and deformed anterolateral portion of the femoral head to
      roll into the acetabulum during abduction alters hip joint mechanics. The
      resultant hinge abduction is associated with pain, and the patient often has
      restricted movement. A valgus osteotomy removes the deformed portion of the
      femoral head away from the weight-bearing area and ensures there is pain-free
      congruent range of movement around the weight-bearing position. The concomitant
      improvement in lever arm function and leg length results in a better gait
      pattern. In immature patients, abolition of hinge abduction allows the lateral
      acetabular ossification center to grow more normally.

PMID- 21742147
TI  - Shelf and/or reduction and containment surgery.
AB  - Hinge abduction occurs early in the fragmentation stage of Legg-Calve-Perthes
      disease and should be suspected when abduction and internal rotation are lost. It
      can be confirmed by an AP radiograph in abduction and internal rotation in which
      the ossific nucleus is not covered by the acetabulum. An arthrogram can then
      yield greater information regarding the reversibility of the hinge abduction.
      Hinge abduction should be considered a contraindication to containment by
      redirectional pelvic or femoral varus osteotomy. However, good results have been
      reported with acetabular augmentation via shelf procedures or Chiari osteotomies.
      Valgus femoral osteotomies have also been beneficial in the treatment of the Legg
      Calve-Perthes hip with hinge abduction.

PMID- 21742148
TI  - Articulated distraction.
AB  - Articular hip distraction can be applied either by using a monolateral
      articulated distractor or a circular fixator. The fixator should be aligned such
      that its axis is aligned with the transverse axis of the hip joint. Following
      distraction, the range of motion is maintained with regular physiotherapy. It is
      a useful salvage procedure in older children with hip stiffness, when other
      methods of containment are not applicable.

PMID- 21742149
TI  - Principles of treating the sequelae of Perthes disease.
AB  - Despite early treatment efforts, many patients with Perthes disease are left with
      residual femoral head deformity, which can be symptomatic with a residual limp
      and poor hip motion. Many such patients can be treated using an extra-articular
      femoral osteotomy. Selecting treatment methods for patients with symptomatic
      Perthes disease with healed but deformed femoral heads has always been difficult
      but is now even more complex because of the new possibilities of femoral head
      neck recontouring and femoral head reduction surgery. Occasionally, patients
      develop osteochondritis dissecans when there is little femoral head deformity.
      The primary objective of management is to establish the exact cause of pain and
      address that cause specifically. This article outlines an approach to these
      patients.

PMID- 21742150
TI  - Treatment of coxa brevis.
AB  - Coxa brevis of the hip results in a morphologic change of the proximal femur
      creating pain and fatigue, leg-length discrepancy, and altered gait. The most
      common cause is a growth alteration of the proximal femoral physis secondary to
      ischemic necrosis of the proximal femoral epiphysis. This article describes the
      Morscher osteotomy-a unique femoral neck-lengthening technique. The outcomes of
      this successful and predictable technique are resolution of symptoms of fatigue
      and hip discomfort; the absence of nonunion, infection, or hardware failure; and
      restoration of normal proximal femoral morphology and biomechanics.

PMID- 21742151
TI  - The treatment of femoral head deformity and coxa magna by the Ganz femoral head
      reduction osteotomy.
AB  - The aspherical coxa magna femoral head can be made more spherical by intra
      articular osteotomy. The Ganz technique of femoral head reduction osteotomy to
      reduce the size and restore the spherical shape of the femoral head has been
      performed in 20 patients over the past 5 years. A good or excellent functional
      and radiographic result was obtained in 14 of the 20. A fair result (decreased
      pain but no improvement in range of motion) occurred in 3, and a poor result
      (stiffness and pain) occurred in 3. The preliminary results of this technique are
      therefore very promising.

PMID- 21742152
TI  - Treatment of the symptomatic healed Perthes hip.
AB  - Healed Legg-Calve-Perthes disease may cause both intra-articular and extra
      articular impingement, resulting in a symptomatic hip prior to the onset of
      osteoarthritis. Various impingement-relieving surgeries have been used in the
      past; however, the development of the safe surgical dislocation technique has
      allowed a better understanding of complex deformity that may be present in these
      hips and hence may improve treatment of these symptomatic prearthritic hips. This
      article outlines the range of deformities possible in a Perthes hip, and
      treatment strategies to surgically address these deformities. For Perthes disease
      good preoperative clinical and radiographic assessment is essential, and
      intraoperative assessment vital.

PMID- 21742153
TI  - Review of total hip resurfacing and total hip arthroplasty in young patients who
      had Legg-Calve-Perthes disease.
AB  - Patients with Legg-Calve-Perthes disease can often be successfully treated with
      femoral head-preserving measures, such as bracing, or containment procedures with
      osteotomies. However, in some cases, after resolution of the disease, the femoral
      head may proceed to collapse or progress to severe arthritis at a young age. If
      nonoperative methods have failed, the only treatment options available for these
      adolescents or young adults may be a total hip resurfacing or a total hip
      arthroplasty (THA). This article focuses on the results and unique technical
      considerations of resurfacing and THA for patients who have severe hip
      osteoarthritis after resolved Legg-Calve-Perthes disease.

PMID- 21742154
TI  - Future biologic treatments for Perthes disease.
AB  - Standard surgical approaches for Perthes disease consist of nonoperative physical
      treatments or surgical treatment. Several investigators have been working on a
      better understanding of the pathophysiology and pathobiology of Perthes disease.
      Most of the focus has been on antiresorptive treatments. Other treatment avenues,
      however, include controlling the inflammatory phase of Perthes disease,
      increasing revascularization of necrotic bone, and anabolic strategies to
      increase bone formation. This article presents a current pathophysiological model
      of Perthes disease, reviews experimental strategies in pharmaceutical treatments,
      and suggests future areas for research.

PMID- 21742155
TI  - Core decompression for juvenile osteonecrosis.
AB  - Core decompression may be used as adjunct for treatment in some cases of Legg
      Calve-Perthes disease (LCPD). The primary application is for patients with onset
      at 12 years of age or older. We recommend classifying these older patients as
      idiopathic juvenile osteonecrosis and treating them similarly to adults with
      avascular necrosis. Juvenile osteonecrosis may benefit from core decompression
      combined with shelf acetabuloplasty during the early stages of necrosis. Younger
      children with LCPD may benefit from decompression by fenestration of the femoral
      head. Experience in adult-onset osteonecrosis and our early experience suggest
      that some patients may benefit from these adjunctive treatments.

PMID- 21742156
TI  - Consensus statements on the management of Perthes disease.

PMID- 21742157
TI  - Quantum computing with NMR.

PMID- 21742158
TI  - Symmetry pathways in solid-state NMR.

PMID- 21742159
TI  - The diabetes pandemic.

PMID- 21742160
TI  - The assault on reproductive rights.

PMID- 21742161
TI  - Inspiring young scientists: a Nobel cause.

PMID- 21742162
TI  - IDF's view of bariatric surgery in type 2 diabetes.

PMID- 21742164
TI  - Tien Yin Wong: tackling the rising burden of diabetic retinopathy.

PMID- 21742165
TI  - Medha Munshi: tailoring diabetes care for older patients.

PMID- 21742166
TI  - Effects of the 2008 recession on health: a first look at European data.

PMID- 21742167
TI  - Phentermine plus topiramate in the treatment of obesity.

PMID- 21742168
TI  - Phentermine plus topiramate in the treatment of obesity.

PMID- 21742170
TI  - Papular-purpuric gloves and socks syndrome.

PMID- 21742208
TI  - ALI and ARDS: challenges and advances.

PMID- 21742209
TI  - Definition of ALI/ARDS.
AB  - Although acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)
      are caused by different injuries and conditions, their similar clinical picture
      makes a compelling case for them to be studied as a single entity. An array of
      potential specific targets for pharmacologic intervention can be applied to
      ALI/ARDS as one disease. Although a working definition of ALI/ARDS that includes
      pulmonary and extrapulmonary causes can have benefit in standardizing supportive
      care, it can also complicate assessments of the efficacy of therapeutic
      interventions. In this article, definitions that have been recently used for
      ALI/ARDS in various clinical studies are discussed individually.

PMID- 21742210
TI  - Epidemiology of ARDS and ALI.
AB  - Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are
      distinctly modern clinical entities. Recent epidemiologic research has taken
      advantage of large cohorts in efforts to better describe these highly lethal
      syndromes with a focus on differentiation of clinically meaningful subtypes and
      early prediction in an effort to improve treatment and prevention. This article
      identifies the most significant studies and systematic reviews of recent years,
      defining the incidence, mortality, risk and prognostic factors, and etiologic
      classes of ARDS/ALI.

PMID- 21742211
TI  - ARDS Network (NHLBI) studies: successes and challenges in ARDS clinical research.
AB  - To hasten the development of effective therapy for acute respiratory distress
      syndrome (ARDS), in 1994, the National Heart, Lung, and Blood Institute initiated
      a clinical network to carry out multicenter clinical trials of ARDS treatments.
      The ARDS Network is a clinical research network of approximately 42 hospitals,
      organized into 12 clinical sites. The goal of the Network is to efficiently test
      promising agents, devices, or management strategies to improve the care of
      patients with ARDS. Comprehensive information regarding all completed and ongoing
      ARDSNet clinical trials is available at www.ardsnet.org, but a brief summary is
      provided in this article.

PMID- 21742212
TI  - Mechanical ventilation with lung protective strategies: what works?
AB  - Essentially all patients with acute lung injury or acute respiratory distress
      syndrome require mechanical ventilatory assistance to support gas exchange and
      reduce the work of breathing associated with the lung impairment. Unfortunately,
      this life-sustaining support may actually cause further lung damage and possibly
      lead to increased mortality. This article reviews strategies that may help
      minimize ventilator-induced lung injury.

PMID- 21742213
TI  - High-frequency oscillatory ventilation in ALI/ARDS.
AB  - In the last 2 decades, our goals for mechanical ventilatory support in patients
      with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) have
      changed dramatically. Several randomized controlled trials have built on a
      substantial body of preclinical work to demonstrate that the way in which we
      employ mechanical ventilation has an impact on important patient outcomes.
      Avoiding ventilator-induced lung injury (VILI) is now a major focus when
      clinicians are considering which ventilatory strategy to employ in patients with
      ALI/ARDS. Physicians are searching for methods that may further limit VILI, while
      still achieving adequate gas exchange.

PMID- 21742214
TI  - Airway pressure release ventilation in acute respiratory distress syndrome.
AB  - Airway pressure release ventilation (APRV) is an alternative mode of ventilation
      that is increasingly used in patients with acute respiratory failure, acute lung
      injury (ALI), and acute respiratory distress syndrome (ARDS). Animal and clinical
      studies have demonstrated that, compared with conventional ventilation, APRV has
      beneficial effects on lung recruitment, oxygenation, end-organ blood flow,
      pulmonary vasoconstriction, and sedation requirements. Further studies, however,
      are required to directly compare APRV to ARDSnet protocol ventilation,
      specifically in patients with ALI/ARDS, and to determine whether managing
      ALI/ARDS with APRV will also achieve mortality reduction.

PMID- 21742215
TI  - Prone-positioning therapy in ARDS.
AB  - The prone position has been used to improve oxygenation in patients with severe
      hypoxemia and acute respiratory failure since 1974. All studies with the prone
      position document an improvement in systemic oxygenation in 70% to 80% of
      patients with acute respiratory distress syndrome (ARDS), with maximal
      improvement seen in the most hypoxemic patients. This article reviews data
      regarding efficacy for use of the prone position in patients with ARDS. Also
      described is a simple, safe, quick, and inexpensive procedure used to prone
      patients with severe ARDS on a standard bed in the intensive care unit at the
      University of Michigan.

PMID- 21742217
TI  - Inhaled nitric oxide and inhaled prostacyclin in acute respiratory distress
      syndrome: what is the evidence?
AB  - The mortality for acute respiratory distress syndrome remains unacceptably high.
      Two vasodilators, inhaled prostacyclin and inhaled nitric oxide, are reviewed in
      this article. Knowledge of inhaled prostacyclin has grown substantially in the
      past 30 years, but less research exists about its utility in acute respiratory
      distress syndrome. Inhaled prostacyclin and other prostaglandin derivatives are
      used in acute respiratory distress syndrome with increasing frequency. Currently,
      only randomized controlled trials exist for inhaled nitric oxide in acute
      respiratory distress syndrome patients. Randomized controlled trials with
      consistent dosing methods are needed for both vasodilators to better define their
      role in the treatment of acute respiratory distress syndrome.

PMID- 21742218
TI  - Glucocorticoid treatment in acute lung injury and acute respiratory distress
      syndrome.
AB  - Experimental and clinical evidence show a strong association between dysregulated
      systemic inflammation and progression of acute respiratory distress syndrome
      (ARDS). This article reviews eight controlled studies evaluating corticosteroid
      treatment initiated before day 14 of ARDS. Available data provide a consistent
      strong level of evidence for improving outcomes. Treatment was also associated
      with a markedly reduced risk of death. This low-cost highly effective therapy is
      well-known, and has a low-risk profile when secondary prevention measures are
      implemented. The authors recommend prolonged methylprednisolone at 1 mg/kg/d
      initially in early ARDS, increasing to 2 mg/kg/d after 7 to 9 days of no
      improvement.

PMID- 21742219
TI  - Extracorporeal CO(2) removal in ARDS.
AB  - Acute respiratory distress syndrome remains one of the most clinically vexing
      problems in critical care. As technology continues to evolve, it is likely that
      extracorporeal CO(2) removal devices will become smaller, more efficient, and
      safer. As the risk of extracorporeal support decreases, devices' role in acute
      respiratory distress syndrome patients remains to be defined. This article
      discusses the functional properties and management techniques of CO(2) removal
      and intracorporeal membrane oxygenation and provides a glimpse into the future of
      long-term gas-exchange devices.

PMID- 21742216
TI  - Surfactant therapy for acute lung injury and acute respiratory distress syndrome.
AB  - This article examines exogenous lung surfactant replacement therapy and its
      usefulness in mitigating clinical acute lung injury (ALI) and the acute
      respiratory distress syndrome (ARDS). Surfactant therapy is beneficial in term
      infants with pneumonia and meconium aspiration lung injury, and in children up to
      age 21 years with direct pulmonary forms of ALI/ARDS. However, extension of
      exogenous surfactant therapy to adults with respiratory failure and clinical
      ALI/ARDS remains a challenge. This article reviews clinical studies of surfactant
      therapy in pediatric and adult patients with ALI/ARDS, focusing on its potential
      advantages in patients with direct pulmonary forms of these syndromes.

PMID- 21742220
TI  - Extracorporeal membrane oxygenation in adult acute respiratory distress syndrome.
AB  - The role of extracorporeal membrane oxygenation (ECMO) in supporting adult
      refractory respiratory failure continues to evolve. Technical advances and the
      clinical challenges of H1N1 associated severe ARDS have spurred a resurgence of
      interest in ECMO. Published systematic review and pooled analyses point out the
      limitations of available studies, however, a growing body of evidence suggest
      potential for benefit. Referral to a specialized center with ECMO experience
      should be considered early after the initiation of high-level ventilator support
      in adult patients with severe ARDS.

PMID- 21742221
TI  - Nutrition therapy for ALI and ARDS.
AB  - The importance of nutrition support in critically ill patients with acute lung
      injury (ALI) and acute respiratory distress syndrome (ARDS) cannot be overstated.
      ALI and ARDS are characterized by a proinflammatory response associated with
      hypercatabolism that could lead to significant nutrition deficits. Nutrition
      support is necessary to prevent cumulative caloric deficits, malnutrition, loss
      of lean body mass, and deterioration of respiratory muscle strength. Furthermore,
      early delivery of enteral nutrition has been associated with the modulation of
      stress and the systemic immune response as well as the attenuation of disease
      severity.

PMID- 21742223
TI  - Recovery and long-term outcome in acute respiratory distress syndrome.
AB  - Interest in longer-term outcomes after acute respiratory distress syndrome (ARDS)
      and the understanding of patterns of recovery have increased enormously over the
      past 10 years. This article highlights important advances in outcomes after ARDS
      and describes pulmonary outcomes, the most recent data on functional and
      neuropsychological disability in patients, health care cost, family caregivers,
      and early models of rehabilitation and intervention.

PMID- 21742222
TI  - Biomarkers in acute lung injury--marking forward progress.
AB  - This article reviews the state of the art regarding biomarkers for prediction,
      diagnosis, and prognosis in acute lung injury. Biomarkers and the goals of
      biomarker research are defined. Progress along 4 general routes is examined.
      First, the results of wide-ranging existing protein biomarkers are reported.
      Second, newer biomarkers awaiting or with strong potential for validation are
      described. Third, progress in the fields of genomics and proteomics is reported.
      Finally, given the complexity and number of potential biomarkers, the results of
      combining clinical predictors with protein and other biomarkers to produce better
      prognostic and diagnostic indices are examined.

PMID- 21742224
TI  - Gene therapy for ALI/ARDS.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are
      characterized by acute respiratory failure and are associated with diverse
      disorders. Gene therapy is a potentially powerful approach to treat diseases
      related to ALI/ARDS, and numerous viral and nonviral methods for gene delivery to
      the lung have been developed. Discussed are recent advances in the development of
      more efficient viral and nonviral gene transfer systems, and the current status
      of gene therapy applied to ALI/ARDS-associated pulmonary diseases is reviewed.
      With the development of more efficient gene therapy vectors, gene therapy is a
      promising strategy for clinical application.

PMID- 21742225
TI  - Mesenchymal stem cells and acute lung injury.
AB  - Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute
      respiratory failure presenting with hypoxemia and bilateral pulmonary
      infiltrates, most often in the setting of pneumonia, sepsis, or major trauma. The
      pathogenesis of ARDS involves lung endothelial injury, alveolar epithelial
      injury, and the accumulation of protein-rich fluid and cellular debris in the
      alveolar space. No pharmacologic therapy has so far proved effective. A potential
      strategy involves cell-based therapies, including mesenchymal stem cells (MSCs).
      Herein we review basic properties of MSCs, their use in preclinical models of
      lung injury and ARDS, and potential therapeutic mechanisms.

PMID- 21742226
TI  - Experimental models and emerging hypotheses for acute lung injury.
AB  - Acute lung injury (ALI) involves the activation of multiple pathways leading to
      lung injury, resolution, and repair. Exploration of the roles of individual
      pathways in humans and animal models has led to a greater understanding of the
      complexity of ALI and the links between ALI and systemic multiorgan failure.
      However, there is still no integrated understanding of the initiation, the
      progression, and the repair of ALI. A better understanding is needed of how
      pathways interact in the human ALI syndrome and how complementary treatments can
      be used to modify the onset, severity, and outcome of ALI in humans.

PMID- 21742227
TI  - Assessing survival benefits from lung transplantation.
AB  - INTRODUCTION: Published studies used several methods to assess the impact of lung
      transplantation on patient survival. To interpret the results of these studies, a
      basic understanding of the models used and underlying hypotheses is required.
      CURRENT KNOWLEDGE: The most often used method consists in assessing the survival
      of waiting-list patients and measuring the impact of lung transplantation on the
      baseline hazard (instantaneous risk) for death, usually with a Cox proportional
      hazards model. This strategy involves strong assumptions about the link between
      the baseline hazard in waiting-list patients and lung transplant recipients.
      Whether these assumptions are true is extremely difficult to establish. Some
      studies compared predicted survival without transplantation to observed survival
      after transplantation. We recently reported a new method in which predicted
      survival without transplantation is compared to predicted survival after
      transplantation. PERSPECTIVES: All the methods described to date evaluate only
      the impact of transplantation on patient survival. The concomitant use of other
      markers such as respiratory function or quality of life would produce a more
      detailed picture of lung transplantation benefits. CONCLUSION: Evaluating the
      benefits of lung transplantation involves the use of complex statistical methods.
      The results should be considered with circumspection, and none of the methods
      described to date allows definitive conclusions.

PMID- 21742228
TI  - Asbestos-related cancer risk in patients with asbestosis or pleural plaques.
AB  - INTRODUCTION: The relationships between benign asbestos-related diseases
      (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim
      of this paper was to review the epidemiological data relevant to this issue.
      CURRENT KNOWLEDGE: Published studies show a significant relationship between
      occupational exposure to asbestos and lung cancer risk, even in the absence of
      abnormalities consistent with asbestosis on the postero-anterior chest x-ray. For
      a given cumulative asbestos exposure, the presence of radiographic evidence of
      asbestosis is associated with an increased risk of lung cancer. Among asbestos
      exposed individuals, those having radiographic evidence of pleural plaques are at
      increased risk for lung cancer and pleural mesothelioma, compared to the general
      population. However, there is no evidence that pleural plaque confers an
      increased risk of lung cancer or pleural mesothelioma within a population of
      individuals having the same cumulative asbestos exposure. PERSPECTIVES: The
      studies identified for this review relied only on chest radiograph data. Studies
      involving accurate evaluations of asbestos exposure and computed tomography of
      the chest are needed. CONCLUSION: Currently available data indicate that patient
      follow-up modalities should be dictated solely by the estimated cumulative
      asbestos exposure and not by the existence of pleural plaques.

PMID- 21742229
TI  - Non-infectious pulmonary complications of myelodysplastic syndromes and chronic
      myeloproliferative disorders.
AB  - INTRODUCTION: Non-infectious pulmonary complications of myelodysplastic syndromes
      and chronic myeloproliferative disorders are not rare but remain little known to
      respiratory physicians who may be confronted with various clinical pictures
      corresponding to different pathophysiological causes. BACKGROUND: The few data in
      the literature only relate to isolated cases or small series. The non-infectious
      pulmonary complications of myelodysplastic syndromes and chronic
      myeloproliferative disorders can be classified into several clinical entities:
      tumour syndrome, pulmonary fibrosis or diffuse infiltrating pneumonia, autoimmune
      reactions including vasculitis, Sweet syndrome, organizing pneumonia, pulmonary
      alveolar proteinosis, pleural effusion and pulmonary arterial hypertension. The
      diagnosis is provided by the histology and management of these complications
      depends on the underlying pathology. VIEWPOINTS AND CONCLUSION: Myelodysplastic
      syndromes and myeloproliferative disorders are entities which are becoming better
      characterized and understood. Better knowledge of the pathophysiological
      mechanisms involved in these complications should improve their diagnosis and
      their management, which still remains complex.

PMID- 21742230
TI  - Assessment of imaging techniques for evaluating small-airway disease in asthma.
AB  - The imaging techniques used to investigate patients with asthma and to assess the
      effects of asthma treatments include computed tomography (CT), helium magnetic
      resonance imaging (MRI), single-photon emission computed tomography (SPECT), and
      positron-emission tomography (PET). Only MRI does not involve radiation exposure.
      Technical improvements in CT, together with the imaging advantages inherent in
      the presence of air in the lung, have diminished the radiation exposure required
      for lung CT. High-resolution low-dose lung CT protocols deliver a dose roughly
      equal to 1 year of natural radiation exposure and can be used even in paediatric
      patients. To date, CT is the most extensively studied lung imaging method, the
      simplest to perform, and the least expensive. In patients with asthma, CT may
      show several structural changes related to small-airway disease including
      cylindrical bronchiolectasis, bronchial wall thickening, and air trapping; an
      indirect marker for bronchiolar obstruction. A robust body of evidence indicates
      that valid CT markers for small-airway disease can be derived from quantitative
      lung density measurements and that these markers correlate with clinical severity
      and lung function test results. In addition, these CT markers are sufficiently
      sensitive to demonstrate therapeutic effects.

PMID- 21742231
TI  - [Antileukotrienes in asthma: a nice story, still to be completed].

PMID- 21742232
TI  - [Asthma exacerbations: what are the issues?].

PMID- 21742233
TI  - [Montelukast in the treatment of mild to moderate persistent asthma].
AB  - INTRODUCTION: Anti-inflammatory preventive treatment is recommended in cases of
      persistent asthma. Besides inhaled corticosteroids (ICS), which represent the
      mainstay of treatment, other therapeutic options are available, of which only
      antileukotrienes are approved for all age groups. BACKGROUND: Given as a
      substitute of low-dose ICS, montelukast prevents exacerbations as efficiently and
      for a longer period than long-acting beta2-agonists. Montelukast is as efficient
      as doubling the dose of ICS on asthma symptoms in cases of inadequate control
      with low-dose ICS. Combined with ICS, it can lead to better control of asthma and
      potentially to ICS sparing. CONCLUSIONS: Given the efficacy, tolerance and long
      term treatment compliance of montelukast in mild persistent asthma in adults and
      children, montelukast, given as a substitute or combined with ICS, could
      contribute to enhanced control of asthma, especially in children.

PMID- 21742234
TI  - [Exposure to asbestos and the indoor environment].
AB  - A link between the inhalation of asbestos fibres and the outcome of benign and
      malignant respiratory diseases has been established from numerous epidemiological
      data in occupational settings. Occupational exposure limit values have been
      established with a gradual lowering of these over time. Conversely, there are few
      epidemiological data dealing with exposure in the indoor environment. However,
      numerous materials and products containing asbestos (MPCA) are present in the
      indoor environment, due to their widespread use in the construction sector in the
      years between 1960 and 1990. The regulations were changed from the late 1990s,
      leading to a systematic inventory of the presence of asbestos-containing
      materials in buildings. The aim of this manuscript is to clarify the different
      types of MPCA encountered in the indoor environment, to describe the techniques
      used to highlight asbestos depending on the nature of the materials, the
      regulatory requirements relating to asbestos in non-occupational situations, and
      to update on the state of knowledge on asbestos-related diseases in the indoor
      environment.

PMID- 21742235
TI  - [Anxiety and depression in COPD: a review].
AB  - INTRODUCTION: COPD does not only affect the respiratory function of a patient. It
      also affects his/her cognitive and affective functions. These effects can be seen
      particularly in the incidence of anxiety and depressive disorders at different
      periods during the stage of the illness. This review of the literature suggests
      some contemporary definitions of these disorders, their link to COPD, and
      procedures for their assessment during clinical practice. BACKGROUND: The
      neurocognitive functions and the emotional resources of the patient are disturbed
      by the insidious development of COPD and the disabling effects that follow. The
      prevalence stands at 50% for anxiety disorders and 33% for depressive disorders.
      These symptoms deteriorate dyspnoea, reduce the exercise tolerance of patients,
      intensify the effects of fatigue, increase emotional instability, alter
      compliance, favor risk behavior in relation to health, and affect communication
      with caregivers. These symptoms also increase the annual number of exacerbations
      and hospitalizations. For practical purposes, while a semidirective clinical
      interview remains the better method to highlight the symptoms, the auto
      questionnaire "hospitalization anxiety depression" has proved to be a reliable
      and sensitive tool. VIEWPOINTS: In patients who do not suffer from a major
      depressive or anxiety disorder (from a source external to COPD) anxiety and
      depressive symptoms reveal a lack of comprehension of the illness, difficulties
      in adjusting psychologically to the illness, misunderstanding and solitude.
      Except for serious cases, in which resort to medication is necessary,
      psychological support is a solution, therapeutic education, acceptance, behavior
      control through rehabilitation and development of the patient-caregiver
      relationship and networks. CONCLUSION: Anxiety and depressive disorders occur at
      any time in the life of a patient suffering from COPD. Health professionals
      should not neglect the signs, thinking them inevitable, attributing them to the
      personality of the patient, the natural evolution of the illness, or ageing.
      Therapeutic solutions exist.

PMID- 21742236
TI  - [Structural abnormalities and inflammation in COPD: a focus on small airways].
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by poorly
      reversible airflow limitation associated with airway remodelling and inflammation
      of both large and small airways. The site of airflow obstruction in COPD is
      located in the small airways, justifying a focus on this compartment. The
      structural abnormalities that are found in bronchioles with a diameter less than
      2mm are characterized by increased airway wall thickness with peribronchial
      fibrosis, and by luminal obstruction by mucous exudates. Destruction of alveolar
      walls, the hallmark of emphysema, may be related to protease-antiprotease
      imbalance, and to mechanisms involving apoptosis, senescence, and autoimmunity.
      Cigarette smoke inhalation triggers the recruitment of innate immune cells
      (neutrophils and macrophages) and putatively adaptive immunity mediated via T and
      B lymphocytes and lymphoid follicles in the small airways. These data suggest a
      potential role for therapies that can target remodelling and inflammation in the
      small airways of patients with COPD.

PMID- 21742237
TI  - [What are the tools for post-occupational follow-up, how should they be performed
      and what are their performance, limits and benefit/risk ratio? Chest X-Ray and CT
      scan].
AB  - Chest radiography and computed tomography (CT) are the two radiological
      techniques used for the follow-up of people exposed to asbestos. Since the last
      conference of consensus (1999), the scientific literature has primarily covered
      high-resolution CT and high-resolution volume CT (HR-VCT). We consider in turn
      the contribution of digital thoracic radiography, recommendations for the
      performance of HR-VCT to ensure the quality of examination while controlling the
      delivered radiation dose, and the need to refer to the "CT atlas of benign
      diseases related to asbestos exposure", published by a group of French experts in
      2007, for interpretation. The results of the published studies concerning
      radiography or CT are then reviewed. We note the great interobserver variability
      in the recognition of pleural plaques and asbestosis, indicating the need for
      adequate training of radiologists, and the importance of defining standardized,
      quantified criteria for CT abnormalities. The very low agreement between thoracic
      and general radiologists must be taken into account. The reading of CT scans in
      cases of occupational exposure to asbestos should be entrusted to thoracic
      radiologists or to general radiologists having validated specific training. A
      double interpretation of CT could be considered in medicosocial requests. CT is
      more sensitive than chest radiography in the detection of bronchial carcinoma but
      generates a great number of false positive results (96 to 99%). No scientific
      data are available to assess the role of imaging by either CT or chest
      radiography in the early detection of mesothelioma.

PMID- 21742238
TI  - [A brief overview of a lung cancer biomarker: thymidylate synthase].
AB  - Thymidylate synthase (TS) is an enzyme, which catalyzes the methylation of
      deoxyuridylate to deoxythymidylate using 5.10-methylenetetrahydrofolate as a
      cofactor. For this reason, TS has been widely investigated and is one of the best
      known drug targets in the anticancer area. Antimetabolites have been developed to
      target TS and among them, pemetrexed is now considered as part of the standard
      treatment for lung cancer and mesothelioma. Intratumoral expression of TS mRNA
      has been shown to be associated with prognosis and with the response to 5-FU
      therapy in patients with breast, colorectal, head and neck cancer types. Recent
      findings suggest that TS might be a biomarker for NSCLC treated with pemetrexed,
      as lower response rates in squamous cell carcinoma and small cell carcinoma may
      be due to a higher expression of TS. Specific validation for this use as a
      biomarker is awaited. All these recent findings suggest that TS could be a useful
      predictive marker of the treatment efficacy of antifolate drugs and indicate that
      both Real-Time PCR and immuno-histochemistry might be used to assess TS
      expression levels. This may help in defining the best therapeutic strategy.

PMID- 21742239
TI  - [Update on diagnosis and treatment of high-risk pulmonary embolism].
AB  - INTRODUCTION: High-risk pulmonary embolism (PE) is associated with a significant
      early mortality, approaching 25%, and is defined by the presence of cardiogenic
      shock. STATE OF THE ART: The high early mortality rate for patients with shock
      requires a rapid diagnostic approach with bedside tests. Right ventricular
      dilatation assessed by echocardiography in patients with a high clinical
      probability for PE confirms the diagnosis without the need for additional
      testing. Spiral CT pulmonary angiography remains the first line investigation for
      patients without shock. Anticoagulant treatment should be started as soon as
      pulmonary embolism is suspected. Fibrinolytic therapy is recommended for patients
      with high-risk pulmonary embolism. The prognostic value of cardiac biomarkers,
      such as B natriuretic peptide, troponins and right ventricular dilatation for
      early mortality has been demonstrated. These markers permit the identification of
      an intermediate risk group of patients with normotensive pulmonary embolism and
      prognostic scores have been developed. PERSPECTIVES: It remains to be established
      whether fibrinolysis can have a clinical benefit or reduce mortality in patients
      with intermediate risk pulmonary embolism. A large randomised placebo-controlled
      study is currently under way to answer this question. Further studies will more
      clearly define the role of various predictive rules to identify patients
      requiring hospital care or those who should be considered for outpatient
      management.

PMID- 21742240
TI  - [Diagnosis of pulmonary embolism].
AB  - Nowadays the diagnosis of pulmonary embolism (PE) is based on a "diagnostic
      strategy" rather than a single test. The first step, after identifying patients
      with suspicion of PE, is to establish the pre-test clinical probability. Several
      scores are available to make a standardised and reproducible assessment of the
      clinical probability and these, therefore, represent valuable diagnostic tools.
      Indeed, it is the clinical probability that guides further investigation. In
      patients with low or intermediate clinical probability, PE can be safely ruled
      out by a negative D-dimer in approximately one-third of patients without
      additional imaging. In the case of a positive D-dimer or high clinical
      probability, CT pulmonary angiography is now the recommended imaging technique.
      However, lower limb venous compression ultrasound and ventilation/perfusion scans
      remain useful in patients with contraindications to CT; mainly those with renal
      insufficiency. In the presence of readily available and strongly validated
      diagnostic strategies, the challenge for the future will probably be better
      identification of patients in whom PE should be suspected.

PMID- 21742241
TI  - [Congenital diaphragmatic hernia: antenatal care].
AB  - The prenatal evaluation of the postnatal prognosis of fetuses displaying
      congenital diaphragmatic hernia (CDH) has improved over the past five years.
      Although the accuracy of these outcome predictions remains a matter of debate, it
      seems important that all teams in charge of those fetuses use the same prognostic
      factors in order to be able to improve and compare their practice. Prediction
      will be based on Lung over Head Ratio (LHR) between 22 and 28 weeks or the LHR
      observed/expected whatever the gestational age, (the measurement of which relies
      on very strict criteria), the position of the liver and lung volumes measured by
      MRI. These factors allow the identification of a group of fetuses likely to have
      a poor outcome. In the group with LHR less than 1 or LHR o/e less than 25% and
      where the liver is in the thorax, survival is less than 20%. In utero treatment
      could be offered to these fetuses. A balloon can be placed in the trachea, under
      the vocal cords, by foetoscopy between 28 and 30 weeks of pregnancy. The balloon
      is retrieved at 34 weeks. The preliminary results show that survival in this
      group increases from 20% to up to 50%. The morbidity does not seem to be
      increased but is currently under evaluation.

PMID- 21742242
TI  - [Acute interstitial pneumonia: diagnostic approach and management].
AB  - Acute interstitial pneumonia (AIP) encompasses a spectrum of pulmonary disorders
      characterized by involvement of the lung interstitium and distal airways
      (bronchioles and alveoli). The onset of respiratory symptoms is acute, most often
      within two weeks. Most AIP take place de novo, but sometimes represent an acute
      exacerbation of chronic lung disease. The clinical presentation of AIP comprises
      rapidly progressive dyspnoea, associated sometimes with cough, fever, myalgia and
      asthenia. Chest radiography shows diffuse pulmonary opacities. The associated
      hypoxemia may be severe enough to cause acute respiratory failure. Underlying
      aetiologies are numerous and variable, particularly in relation to the underlying
      immune status of the host. Various histopathological entities may be responsible
      for AIP although diffuse alveolar damage is the predominant pattern. The
      diagnostic approach to a patient presenting with AIP is to try to determine the
      most likely underlying histopathological pattern and to search for a precise
      aetiology. It relies mainly on a meticulous clinical evaluation and accurate
      biological investigation, essentially guided by the results of bronchoalveolar
      lavage performed in an area identified by abnormalities on high resolution
      computed tomography of the lungs. Initial therapeutic management includes
      symptomatic measures, broad-spectrum antibiotic treatment adapted to the clinical
      context, frequently combined with systemic corticosteroid therapy.

PMID- 21742243
TI  - [New tests for the diagnosis of tuberculosis].
AB  - Over the last decade, molecular biology techniques for identifying mycobacteria
      in pulmonary secretions have become more and more sensitive and rapid, even in
      smear negative samples. Nuclear amplification techniques also allow the rapid
      detection of resistance to first or second line anti-tuberculous drugs. The
      sensitivity of these techniques for non respiratory samples is yet to be
      determined. The diagnosis of latent tuberculous infection (LTBI) has also
      increased in sensitivity, specificity and positive predictive value through the
      use of interferon-gamma release assays (IGRAs), which are tending to replace the
      tuberculin skin test, except for children aged under five. These tests, however,
      do have limitations which are important for the clinician; especially their
      inability to distinguish active from latent tuberculosis and their inability, in
      most circumstances, to exclude a diagnosis of active TB.

PMID- 21742244
TI  - [Exacerbations of asthma in pregnant women].
AB  - Prevention of exacerbations and effective treatment is essential in pregnant
      asthmatic women. The management is well documented. Misunderstanding of the
      recommendations leads to unsuitable, insufficient treatment and is responsible
      for more frequent recurrences in the pregnant woman compared with the non
      pregnant. Above all, good control of the disease and the prevention of
      exacerbations, based on inhaled corticosteroid therapy and smoking cessation,
      reduces complications, in particular prematurity and low birth weight.

PMID- 21742245
TI  - Enterovirus 71 vaccine: when will it be available?

PMID- 21742246
TI  - Role of glucose-regulated Protein 78 in embryonic development and neurological
      disorders.
AB  - Glucose-regulated protein 78 (GRP78) is an important chaperone protein that is
      predominantly expressed in the endoplasmic reticulum. The multifunctional roles
      of GRP78 in protein folding, endoplasmic reticulum calcium binding,
      cytoprotection, and anti-apoptosis, as well as its function as a receptor on the
      cell surface, disclose its major involvement in physiological and numerous
      pathological conditions. Recent advances in mouse models targeting GRP78 allele
      have revealed the essential roles of GRP78 in development and neurological
      disorders, as well as accurate neural migration and neuroprotection. This review
      of correlation between GRP78 and embryogenesis and neurological disorders
      provides further directions for investigation, as well as potential therapeutics
      for clinical use.

PMID- 21742247
TI  - Pilot study of twice-weekly therapy for pulmonary tuberculosis in Taiwan.
AB  - BACKGROUND/PURPOSE: Taiwan has never implemented supervised intermittent
      chemotherapy for pulmonary tuberculosis, and its application and results are
      unknown. The purpose of this study was to evaluate the efficacy and feasibility
      of a 62-dose, four-drug, 6-month, twice-weekly regimen administered by directly
      observed therapy for the treatment of pulmonary tuberculosis. METHODS: From
      January 2004 through December 2006, a total of 116 patients with suspected or
      confirmed pulmonary tuberculosis were enrolled. Thirty-two of these patients were
      excluded from the analysis because of drug resistance, negative culture, self
      withdrawal and drug reactions. Isoniazid, rifampin, pyrazinamide, and ethambutol
      were administered daily for 2 weeks, followed by twice weekly at a higher dose
      for 6 weeks. Thereafter, isoniazid, ethambutol and rifampin were administered
      twice weekly for 18 weeks. Treatment was directly observed by nurses or outreach
      workers. RESULTS: Of the 84 evaluable patients, 75 [89.3%, 95% confidence
      interval (CI): 80.6s-95.0%] patients were considered as successfully treated,
      three (3.6%, 95% CI: 0.7-10.1%) transferred out, five (6.0%, 95% CI: 2.0-13.3%)
      were unsuccessful and one (1.2%, 95% CI: 0.03-6.5%) died. Five patients were
      treatment failure (6.0%, 95% CI: 2.0-13.3%). Three patients had recurrences of
      pulmonary tuberculosis, and the recurrences were 4, 6 and 15 months after the
      completion of therapy. Sixpatients (5.2%) had severe adverse drug reactions and
      had their regimen modified. CONCLUSION: Prior to this study, intermittent therapy
      has not been attempted in Taiwan. This four-drug mostly twice-weeldy pulmonary
      tuberculosis treatment regimen is efficacious and relatively nontoxic, with a
      higher treatment success rate and a lower death rate. It considerably simplifies
      treatment and facilitates the execution of directly observed therapy. The reasons
      for the relatively high failure rate require further studies.

PMID- 21742248
TI  - A case-control study of HIV infection among incarcerated female drug users:
      impact of sharing needles and having drug-using sexual partners.
AB  - BACKGROUND/PURPOSE: Taiwan experienced a rapid surge in human immunodeficiency
      virus (HIV) among injection drug users (IDUs) from 2003 to 2005. The male-to
      female ratio of HIV cases decreased from 20:1 in 2003 to 6:1 in 2006. This change
      is primarily due to increasing numbers of female injection drug users in Taiwan.
      Our primary objective was to identify the risk factors associated with HIV
      infection among incarcerated female drug users. METHODS: A case-control design
      involved recruitment of all eligible HIV-infected female inmates from all 24
      prisons in Taiwan from November to December, 2007. Eligible HIV seronegative
      controls were chosen within the same prison and matched to the cases by age
      (within 3 years) and by history of illicit drug use. A subsample of these matches
      was randomly selected since there were many more eligible controls than HIV
      infected cases. An anonymous self-administered questionnaire was completed with
      assistance from trained research assistants. RESULTS: A total of 114 cases and
      149 control participants were recruited, with a response rate of 82% and 54%.
      Injectable heroin use was significantly greater (p = 0.02) among HIV-infected
      cases (93.0%) than un-infected controls (84.6%). Compared to seronegative
      controls, HIV-infected cases were more likely to share drug paraphernalia and
      have drug-using sexual partners. Multiple logistic regression analysis revealed
      that the number of imprisonments (between 2-5 times; OR = 5.23), sharing mainly
      dilutes (OR= 63.47), and sharing dilutes concurrently with needles (OR= 127.33)
      significantly predicted HIV seroconversion, after controlling for age and years
      of education. CONCLUSION: Sharing needles/dilutes and practicing unsafe
      intercourse with drug-using sexual partners places female drug users at
      considerable risk.

PMID- 21742249
TI  - Effect of immediate and delayed post space preparation on apical leakage using
      three root canal obturation techniques after rotary instrumentation.
AB  - BACKGROUND/PURPOSE: For teeth that have undergone root canal therapy post
      fabrication and subsequent crown restoration are often required to increase
      strength. It is necessary to remove a portion of gutta-percha during post space
      preparation that may cause displacement of the root canal fillings and affect
      their sealing ability. This study evaluated the effects of different post space
      preparation time intervals and root canal obturation techniques on the apical
      sealing ability of filled root canals. METHODS: One hundred single-canal teeth
      were incrementally crown-down enlarged to an apical diameter of 0.40 mm with 0.06
      taper by K3 rotary instrumentation, combined with 5.25% NaOCl irrigation. The
      teeth were randomized into four groups: 30 obturated by lateral compaction
      technique (Group 1); 30 by vertical compaction technique (Group 2); 30 by
      injectable thermoplasticized gutta-percha technique (Group 3); and 10 controls
      with no obturation (Group 4). All specimens were stored in 100% humidity at 37
      degrees C. Immediately and 3 days and 7 days after obturation, post space was
      made utilizing heated pluggers, and leaving a 5.0-mm gutta-percha filling. The
      teeth were immersed in 2.0% methylene blue solution for 72 hours, and finally cut
      longitudinally in half. Dye leakage was examined under a stereomicroscope. The
      results were recorded and statistically analyzed. RESULTS: The mean distance of
      dye leakage after post space preparation at three different time intervals in
      Group 1 were greater than those in Groups 2 and 3. One-way analysis of variance
      indicated that the apical seal or adaptation of vertical compaction technique and
      injectable thermoplasticized gutta-percha technique were not easy to break during
      post space preparation. CONCLUSION: Teeth treated by vertical compaction and
      injectable thermoplasticized gutta-percha techniques showed less leakage than
      those treated by lateral compaction. The least amount of dye leakage existed when
      the post space preparation was made on day 7 after root canal obturation.

PMID- 21742250
TI  - Percutaneous computed tomography-guided cryotherapy of thoracic masses in
      nonsurgical candidates: experience in 19 patients.
AB  - BACKGROUND/PURPOSE: Percutaneous cryotherapy has become a minimally invasive
      treatment option for unresectable lung malignancies. We report the experience and
      outcomes with percutaneous computed tomography (CT)-guided cryotherapy of primary
      lung malignancies, as well as recurrence and metastases, in patients ineligible
      for surgery. METHODS: The procedure was performed after administration of local
      anesthesia on 23 tumors in 19 patients (10 male and 9 female patients; mean age,
      58.7 years). None of the patients were surgical candidates and underwent CT
      guided percutaneous cryotherapy for treatment of the malignant mass in the lung.
      Visualization of low-attenuation ice ball formation was performed using CT
      scanning after each cycle of freezing and thawing therapy. Subsequent CT scans
      were scheduled at 3-month intervals post-procedure to assess tumor control.
      RESULTS: No lethal complication, major bleeding or bronchial damage was observed
      in any of the 23-cryotherapy sessions performed. Three patients developed
      pneumothorax and one patient required chest tube insertion. Thirteen tumors
      (56.5%) regressed, including two complete responses, five tumors (21.7%) were
      stationary and the remaining five tumors (21.7%) were found to be progressing at
      the 3-month follow-ups. No recurrence was found in the 11 regressed tumors for 6
      months, and there was also no recunence in the two tumors that completely
      responded up to 12 months later with a satisfactory procedure. CONCLUSION:
      Percutaneous cryotherapy for primary lung cancer, recurrence and metastatic lung
      tumors is feasible and safe for local control.

PMID- 21742251
TI  - Impact of transcatheter closure of atrial septal defects in pediatric patients on
      body weight.
AB  - BACKGROUND/PURPOSE: Pediatric patients with atrial septal defect (ASD) may have
      failure to thrive. This study aimed to investigate body weight changes in
      pediatric patients after transcatheter closure of ASD. METHODS: From June 2003 to
      September 2008, we enrolled 60 pediatric patients who underwent transcatheter
      closure of ASD. Changes in body weight percentile, heart rate, and resolution of
      right ventricular hypertrophy were compared before and after ASD closure.
      Patients were divided into two groups according to initial weight percentile:
      group A, <50(th) percentile (n = 39) and group B, >=50(th) percentile (n = 21).
      Echocardiography and routine weight measurements were performed before the
      procedure and at 3, 6, and 12 months during follow-up. Clinical presentations,
      laboratory data, and outcomes were measured. RESULTS: Increased body weight
      percentile (41+/-4 vs. 48+/-4, p<0.01), lower heart rate (100+/-2 beats/min vs.
      89+/-2beats/min, p<0.01), and resolution of right ventricular hypertrophy (59/60
      vs. 1/60, p<0.01) were achieved after ASD closure at the 12-month follow-up.
      Patients in group A were significantly younger (4.6+/-0.5 years vs. 7.0+/-0.9
      years, p = 0.016), had a higher pulmonary/systemic blood flow ratio (2.2+/-0.1
      vs. 1.8+/-0.l, p = 0.044), a largerratio of ASD diameter/body surface area
      (25.0+/-1.4 vs. 16.4+/-1.9, p<0.01), and higher percentage of weight gain
      increase >= 5 percentile compared with patients in group B (22/39 vs. 6/21, p =
      0.039). CONCLUSION: Transcatheter closure of ASD positively affects weight gain.
      An increase of 7 percentile weight was observed at 1 year of follow-up. Patients
      with a younger age, higher pulmonary/systemic blood flow ratio, and a larger
      ratio of ASD diameter/body surface area may have better weight gain after ASD
      closure.

PMID- 21742252
TI  - Anti-neutrophil cytoplasmic antibody-associated Pauci-immune crescentic
      glomerulonephritis complicating Sjogren's syndrome.
AB  - Sjogren's syndrome is a chronic autoimmune disease, characterized by specific
      autoimmune antibodies anti-Ro and anti-La, and it can involve multiple organs,
      such as the kidneys, lungs, muscles, and nervous system. The most common renal
      complication of Sjogren's syndrome is tubulointerstitial nephritis, and
      glomerulonephritis is relatively uncommon. We report the case of an 86-year-old
      man presenting with recurrent fever, poor appetite, decreased salivary secretion,
      and body weight loss. Laboratory investigation revealed that serum creatinine was
      4.2 mg/dL, proteinuria was 3+, and there was microscopic hematuria. Positive
      perinuclear anti-neutrophil cytoplasmic antibody, anti-Ro, and anti-La antibodies
      were detected. Renal biopsy showed crescentic glomerulonephritis with scanty
      immune complex deposition. The patient was diagnosed with primary Sjogren's
      syndrome complicated with rapidly progressive glomerulonephritis with positive
      anti-neutrophil cytoplasmic antibody. Unlike the patients of other case reports,
      our patient's renal function did not recover after immunosuppressant treatment,
      and he finally received long-term hemodialysis. Pauci-immune glomerulonephritis
      is a rare renal complication of Sjogren's syndrome, and progress to renal failure
      in such patients is possible.

PMID- 21742253
TI  - Comparison of antidepressant efficacy-related SNPs among Taiwanese and four
      populations in the HapMap database.
AB  - The genetic influence of single nucleotide polymorphisms (SNPs) on antidepressant
      efficacy has been previously demonstrated. To evaluate whether there are ethnic
      differences, we compared the allele frequencies of antidepressant efficacy
      related SNPs between the Taiwanese population and four other populations in the
      HapMap database. We recruited 198 Taiwanese major depression patients and 106
      Taiwanese controls. A panel of possible relevant SNPs (in brain-derived
      neurotrophic factor, 5-hydroxytryptamine receptor 2A, interleukin 1 beta, and G
      protein beta 3 subunit genes) was selected for comparisons of allele frequencies
      using the chi(2) test. Our results suggested no difference between Taiwanese
      patients and controls, but there were significant differences among Taiwanese
      controls and the other four ethnic groups in brain-derived neurotrophic factor, 5
      hydroxytryptamine receptor 2A, interleukin 1 beta and G-protein beta 3 subunit
      genes. We conclude that there are ethnic differences in the allele frequencies of
      antidepressant efficacy-related SNPs, and that the degree of variations is
      consistent with geographic distances. Further investigation is required to verify
      the attribution of genetic differences to ethnic-specific antidepressant
      responses.

PMID- 21742254
TI  - Diagnostic usefulness of an enzyme-linked immunospot assay for interferon-gamma
      in extrapulmonary tuberculosis.

PMID- 21742255
TI  - A new piece in the 3D Jigsaw of malaria parasite.
AB  - The structural insights presented by Hansen et al. in this issue of Structure on
      how a key malaria parasite protease is blocked by its inhibitor may provide a
      flicker of hope in the desperate struggle to develop drugs against one of the
      most severe health problems.

PMID- 21742256
TI  - The endless subtleties of RNA-protein complexes.
AB  - New NMR structures of complexes between double-strand RNA binding domains and
      their RNA hairpin substrates reported by Wang et al. in this issue of Structure
      reveal striking adaptations in both the protein recognition element and in the
      RNA.

PMID- 21742257
TI  - Pass the jelly rolls.
AB  - The crystal structure of the vaccinia virus D13 protein presented by Bahar et al.
      in this issue of Structure displays fused "virus jelly roll" folds, ubiquitous
      among dsDNA icosahedral viruses. Although D13 is not present in the mature virus,
      its structure suggests its evolutionary descent from an ancient icosahedral
      ancestor.

PMID- 21742258
TI  - Dynamic allostery: linkers are not merely flexible.
AB  - Most proteins consist of multiple domains. How do linkers efficiently transfer
      information between sites that are on different domains to activate the protein?
      Mere flexibility only implies that the conformations would be sampled. For fast
      timescales between triggering events and cellular response, which often involves
      large conformational change, flexibility on its own may not constitute a good
      solution. We posit that successive conformational states along major allosteric
      propagation pathways are pre-encoded in linker sequences where each state is
      encoded by the previous one. The barriers between these states that are
      hierarchically populated are lower, achieving faster timescales even for large
      conformational changes. We further propose that evolution has optimized the
      linker sequences and lengths for efficiency, which explains why mutations in
      linkers may affect protein function and review the literature in this light.

PMID- 21742259
TI  - Structural basis for the regulation of cysteine-protease activity by a new class
      of protease inhibitors in Plasmodium.
AB  - Plasmodium cysteine proteases are essential for host-cell invasion and egress,
      hemoglobin degradation, and intracellular development of the parasite. The
      temporal, site-specific regulation of cysteine-protease activity is a
      prerequisite for survival and propagation of Plasmodium. Recently, a new family
      of inhibitors of cysteine proteases (ICPs) with homologs in at least eight
      Plasmodium species has been identified. Here, we report the 2.6 A X-ray crystal
      structure of the C-terminal, inhibitory domain of ICP from P. berghei (PbICP-C)
      in a 1:1 complex with falcipain-2, an important hemoglobinase of Plasmodium. The
      structure establishes Plasmodium ICP as a member of the I42 class of chagasin
      like protease inhibitors but with large insertions and differences in the binding
      mode relative to other family members. Furthermore, the PbICP-C structure
      explains why host-cell cathepsin B-like proteases and, most likely, also the
      protease-like domain of Plasmodium SERA5 (serine-repeat antigen 5) are no targets
      for ICP.

PMID- 21742260
TI  - Protein-RNA and protein-protein recognition by dual KH1/2 domains of the neuronal
      splicing factor Nova-1.
AB  - Nova onconeural antigens are neuron-specific RNA-binding proteins implicated in
      paraneoplastic opsoclonus-myoclonus-ataxia (POMA) syndrome. Nova harbors three K
      homology (KH) motifs implicated in alternate splicing regulation of genes
      involved in inhibitory synaptic transmission. We report the crystal structure of
      the first two KH domains (KH1/2) of Nova-1 bound to an in vitro selected RNA
      hairpin, containing a UCAG-UCAC high-affinity binding site. Sequence-specific
      intermolecular contacts in the complex involve KH1 and the second UCAC repeat,
      with the RNA scaffold buttressed by interactions between repeats. Whereas the
      canonical RNA-binding surface of KH2 in the above complex engages in protein
      protein interactions in the crystalline state, the individual KH2 domain can
      sequence-specifically target the UCAC RNA element in solution. The observed
      antiparallel alignment of KH1 and KH2 domains in the crystal structure of the
      complex generates a scaffold that could facilitate target pre-mRNA looping on
      Nova binding, thereby potentially explaining Nova's functional role in splicing
      regulation.

PMID- 21742261
TI  - NusA interaction with the alpha subunit of E. coli RNA polymerase is via the UP
      element site and releases autoinhibition.
AB  - Elongating Escherichia coli RNAP is modulated by NusA protein. The C-terminal
      domain (CTD) of the RNAP alpha subunit (alphaCTD) interacts with the acidic CTD 2
      (AR2) of NusA, releasing the autoinhibitory blockade of the NusA S1-KH1-KH2 motif
      and allowing NusA to bind nascent nut spacer RNA. We determined the solution
      conformation of the AR2:alphaCTD complex. The alphaCTD residues that interface
      with AR2 are identical to those that recognize UP promoter elements A nusA
      DeltaAR2 mutation does not affect UP-dependent rrnH transcription initiation in
      vivo. Instead, the mutation inhibits Rho-dependent transcription termination at
      phage lambdatR1, which lies adjacent to the lambdanutR sequence. The Rho
      dependent lambdatimm terminator, which is not preceded by a lambdanut sequence,
      is fully functional. We propose that constitutive binding of NusA-DeltaAR2 to
      lambdanutR occludes Rho. In addition, the mutation confers a dominant defect in
      exiting stationary phase.

PMID- 21742262
TI  - Protein-protein complex structure predictions by multimeric threading and
      template recombination.
AB  - The total number of protein-protein complex structures currently available in the
      Protein Data Bank (PDB) is six times smaller than the total number of tertiary
      structures in the PDB, which limits the power of homology-based approaches to
      complex structure modeling. We present a threading-recombination approach, COTH,
      to boost the protein complex structure library by combining tertiary structure
      templates with complex alignments. The query sequences are first aligned to
      complex templates using a modified dynamic programming algorithm, guided by ab
      initio binding-site predictions. The monomer alignments are then shifted to the
      multimeric template framework by structural alignments. COTH was tested on 500
      nonhomologous dimeric proteins, which can successfully detect correct templates
      for 50% of the cases after homologous templates are excluded, which significantly
      outperforms conventional homology modeling algorithms. It also shows a higher
      accuracy in interface modeling than rigid-body docking of unbound structures from
      ZDOCK although with lower coverage. These data demonstrate new avenues to model
      complex structures from nonhomologous templates.

PMID- 21742263
TI  - Allostery in protein domains reflects a balance of steric and hydrophobic
      effects.
AB  - Allosteric conformational change underlies biological function in many proteins.
      Allostery refers to a conformational event in which one region of a protein
      undergoes structural rearrangement in response to a stimulus applied to a
      different region of the same protein. Here, I show for a variety of proteins that
      a simple, phenomenological model of the dependence of protein conformation on
      hydrophobic burial energy allows one to compute low-energy conformational
      fluctuations for a given sequence by using linear programming to find optimized
      combinations of sequence-specific hydrophobic burial modes that satisfy steric
      constraints. From these fluctuations one may calculate allosteric couplings
      between different sites in a protein domain. Although the physical basis of
      protein structure is complex and multifactorial, a simplified description of
      conformational energy in terms of the hydrophobic effect alone is sufficient to
      give a mechanistic explanation for many biologically important allosteric events.

PMID- 21742264
TI  - Fragment-based phase extension for three-dimensional structure determination of
      membrane proteins by electron crystallography.
AB  - In electron crystallography, membrane protein structure is determined from two
      dimensional crystals where the protein is embedded in a membrane. Once large and
      well-ordered 2D crystals are grown, one of the bottlenecks in electron
      crystallography is the collection of image data to directly provide experimental
      phases to high resolution. Here, we describe an approach to bypass this
      bottleneck, eliminating the need for high-resolution imaging. We use the
      strengths of electron crystallography in rapidly obtaining accurate experimental
      phase information from low-resolution images and accurate high-resolution
      amplitude information from electron diffraction. The low-resolution experimental
      phases were used for the placement of alpha helix fragments and extended to high
      resolution using phases from the fragments. Phases were further improved by
      density modifications followed by fragment expansion and structure refinement
      against the high-resolution diffraction data. Using this approach, structures of
      three membrane proteins were determined rapidly and accurately to atomic
      resolution without high-resolution image data.

PMID- 21742265
TI  - Interconversion of two GDP-bound conformations and their selection in an Arf
      family small G protein.
AB  - ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate
      in many cellular functions via their characteristic GTP/GDP conformational
      cycles, during which a nucleotide(*)Mg(2+)-binding site communicates with a
      remote N-terminal helix. However, the conformational interplay between the
      nucleotides, the helix, the protein core, and Mg(2+) has not been fully
      delineated. Herein, we report a study of the dynamics of an Arf-family protein,
      Arl8, under various conditions by means of NMR relaxation spectroscopy. The data
      indicated that, when GDP is bound, the protein core, which does not include the N
      terminal helix, reversibly transition between an Arf-family GDP form and another
      conformation that resembles the Arf-family GTP form. Additionally, we found that
      the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned
      former and latter conformations in a population-shift manner. Given the dynamics
      of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of
      an energy diagram.

PMID- 21742266
TI  - Structure of a yeast RNase III dsRBD complex with a noncanonical RNA substrate
      provides new insights into binding specificity of dsRBDs.
AB  - dsRBDs often bind dsRNAs with some specificity, yet the basis for this is poorly
      understood. Rnt1p, the major RNase III in Saccharomyces cerevisiae, cleaves RNA
      substrates containing hairpins capped by A/uGNN tetraloops, using its dsRBD to
      recognize a conserved tetraloop fold. However, the identification of a Rnt1p
      substrate with an AAGU tetraloop raised the question of whether Rnt1p binds to
      this noncanonical substrate differently than to A/uGNN tetraloops. The solution
      structure of Rnt1p dsRBD bound to an AAGU-capped hairpin reveals that the
      tetraloop undergoes a structural rearrangement upon binding to Rnt1p dsRBD to
      adopt a backbone conformation that is essentially the same as the AGAA tetraloop,
      and indicates that a conserved recognition mode is used for all Rnt1p substrates.
      Comparison of free and RNA-bound Rnt1p dsRBD reveals that tetraloop-specific
      binding requires a conformational change in helix alpha1. Our findings provide a
      unified model of binding site selection by this dsRBD.

PMID- 21742267
TI  - Insights into the evolution of a complex virus from the crystal structure of
      vaccinia virus D13.
AB  - The morphogenesis of poxviruses such as vaccinia virus (VACV) sees the virion
      shape mature from spherical to brick-shaped. Trimeric capsomers of the VACV D13
      protein form a transitory, stabilizing lattice on the surface of the initial
      spherical immature virus particle. The crystal structure of D13 reveals that this
      major scaffolding protein comprises a double beta barrel "jelly-roll" subunit
      arranged as pseudo-hexagonal trimers. These structural features are
      characteristic of the major capsid proteins of a lineage of large icosahedral
      double-stranded DNA viruses including human adenovirus and the bacteriophages
      PRD1 and PM2. Structure-based phylogenetic analysis confirms that VACV belongs to
      this lineage, suggesting that (analogously to higher organism embryogenesis)
      early poxvirus morphogenesis reflects their evolution from a lineage of viruses
      sharing a common icosahedral ancestor.

PMID- 21742268
TI  - The structure of E. coli IgG-binding protein D suggests a general model for
      bending and binding in trimeric autotransporter adhesins.
AB  - The Escherichia coli Ig-binding (Eib) proteins are trimeric autotransporter
      adhesins (TAAs) and receptors for IgG Fc. We present the structure of a large
      fragment of the passenger domain of EibD, the first TAA structure to have both a
      YadA-like head domain and the entire coiled-coil stalk. The stalk begins as a
      right-handed superhelix, but switches handedness halfway down. An unexpected beta
      minidomain joins the two and inserts a ~120 degrees  rotation such that there is
      no net twist between the beginning and end of the stalk. This may be important in
      folding and autotransport. The surprisingly large cavities we found in EibD and
      other TAAs may explain how TAAs bend to bind their ligands. We identified how IgA
      and IgG bind and modeled the EibD-IgG Fc complex. We further show that EibD
      promotes autoagglutination and biofilm formation and forms a fibrillar layer
      covering the cell surface making zipper-like contacts between cells.

PMID- 21742269
TI  - Omentin: a novel link between inflammation, diabesity, and cardiovascular
      disease.
AB  - Obesity has reached pandemic proportions and is associated with serious
      cardiometabolic sequelae including insulin resistance, diabetes, dyslipidemia,
      hypertension, and cardiovascular disease, where adipose tissue-secreted
      cytokines, that is, adipokines, have been implicated in these processes. Omentin
      is a novel adipokine preferentially produced by visceral adipose tissue with
      insulin-sensitizing effects, where circulating levels are decreased in insulin
      resistant states, for example, obesity and diabetes. With respect to vascular
      biology, omentin causes vasodilatation of blood vessels and attenuates C-reactive
      protein-induced angiogenesis potentially via the nuclear factor B signaling
      pathway, a potent proinflammatory signaling pathway. Thus, omentin may have
      beneficial effects on the metabolic syndrome and could potentially be used as a
      biologic marker and/or pharmacologic agent in this respect.

PMID- 21742270
TI  - Calcineurin and electrical remodeling in pathologic cardiac hypertrophy.
AB  - Calcineurin is a cytoplasmic Ca(2+)/calmodulin-dependent protein phosphatase that
      contributes to cardiac hypertrophy. Numerous studies have demonstrated that
      calcineurin/nuclear factor of activated T cell pathway affects the architecture
      of the heart under pathologic conditions, and the effects of calcineurin/nuclear
      factor of activated T cell pathway on cardiac hypertrophy have been well
      reviewed. Cardiac electrical remodeling is generally accompanied with the cardiac
      hypertrophy, and alteration of cardiac ion channel activity also leads to the
      changes of calcineurin activity and cardiac hypertrophy. Many studies have linked
      calcineurin with changes of a variety of ion channels, but the therapeutic
      approaches to target calcineurin for correcting cardiac electrical disturbance
      have not been formulated. Here, we review the recent progress in calcineurin and
      electrical remodeling in pathologic cardiac hypertrophy.

PMID- 21742271
TI  - From atherosclerosis to acute coronary syndromes: the role of soluble CD40
      ligand.
AB  - The binding of CD40 ligand (CD40L) to CD40 stimulates inflammatory processes
      including the release of proinflammatory cytokines and the expression of adhesion
      molecules implying a role in atherosclerosis. Patients exhibiting
      hypercholesterolemia, unstable angina, or acute myocardial infarction present
      with increased CD40L levels. Novel data suggest that elevated soluble CD40L
      levels not only represent a risk factor for cardiovascular disease but also
      predict future adverse events, especially in patients with acute coronary
      syndromes (ACS). Examination of the potential role of the genetic variability on
      CD40/CD40L genes in ACS, as regards the regulation of CD40L, appears to be of
      great interest. Moreover, several therapeutic approaches such as statins,
      antihypertensive agents, and antiplatelet agents have been suggested as potential
      modulators of CD40L levels anticipating a positive impact on the outcomes of
      patients with ACS. Whether specific agents target the CD40/CD40L system as well
      as its pathogenic role in ACS remains to be elucidated by large-scale studies in
      the future.

PMID- 21742272
TI  - The atrioventricular node: origin, development, and genetic program.
AB  - The sinus node generates the electrical impulse, which spreads rapidly over both
      atria, causing them to contract simultaneously. In the normal heart, a layer of
      connective tissue electrically insulates the atria and ventricles. The only
      pathway that crosses this plane is the atrioventricular conduction axis, through
      which the impulse reaches the ventricles. Within the axis, the atrioventricular
      node delays the impulse, allowing the ventricles to be filled before their
      contraction is initiated. Moreover, the atrioventricular node protects the
      ventricles from rapid atrial arrhythmias and may take over pacemaker function
      when the sinus node fails. In pathological conditions, these complex
      physiological properties contribute to several types of arrhythmias that
      originate from the atrioventricular conduction system. One example is
      atrioventricular block, which requires electronic pacemaker implantation because
      there is currently no cure for this arrhythmia. Because conduction system defects
      may arise during embryonic development, the mechanisms of conduction system
      development have been intensively studied. Nevertheless, its developmental
      origin, molecular composition, and phenotype have remained fertile subjects of
      research and debate. Lineage and expressional analyses have indicated that the
      atrioventricular node develops from a subpopulation of precursor cells in the
      dorsal part of the embryonic atrioventricular canal. These cells become distinct
      early in development, are less well differentiated compared to the developing
      working myocardium, and, in addition to their cardiogenic gene program, activate
      and maintain a neurogenic gene program.

PMID- 21742273
TI  - Targeting phosphatidylcholine-specific phospholipase C for atherogenesis therapy.
AB  - Atherosclerosis, a dynamic and progressive vascular disease arising from the
      combination of endothelial dysfunction and inflammation, is becoming a major
      killer in the 21st century. Accumulating evidence implicates phosphatidylcholine
      specific phospholipase C (PC-PLC) in endothelial dysfunction and several
      inflammation processes. In addition, in a recent study, we demonstrated that PC
      PLC contributed to the progression of atherosclerosis. Considering the important
      roles of PC-PLC in vascular endothelial cell dysfunction and its proinflammatory
      properties, we propose that a pharmacological blockade of PC-PLC represents a
      rational approach to atherosclerosis therapy.

PMID- 21742274
TI  - Characterization of the inflammatory phenotype in atherosclerosis may contribute
      to the development of new therapeutic and preventative interventions.
AB  - Growing evidence supports a major role of chronic inflammation and platelet
      activation in the development of atherosclerosis and cardiovascular (CV) disease.
      Because CV dysfunction is, at least in part, reversible, identifying these early
      stages may enhance the development of new therapeutic and preventive
      interventions. Technological advances have led to appreciation of underlying
      pathophysiology in vivo via targeted clinical readouts by soluble markers and
      noninvasive imaging. Integration of these readouts in early phases of development
      of novel drug candidates may provide a key addition to translational steps toward
      robust evidence. New paradigms of drug discovery may lead to earlier and more
      targeted interventions at reversible stage of disease.

PMID- 21742275
TI  - Inequal measure?

PMID- 21742276
TI  - Massage therapy in post-operative rehabilitation of children and adolescents with
      cerebral palsy - a pilot study.
AB  - AIM: The purpose of this pilot study was to explore the use of massage therapy in
      children with cerebral palsy undergoing post-operative rehabilitation. MATERIAL
      AND METHOD: Three participants were randomized to massage therapy and another
      three participants to rest. All children had undergone surgery in one or two
      lower limbs. Pain, wellbeing, sleep quality, heart rate and qualitative data were
      collected for each child. RESULTS: The scores of pain intensity and discomfort
      were low in all participants. Heart rate decreased in participants who were
      randomized to rest, but no change was found in the massage therapy group.
      CONCLUSIONS: The lack of decrease in heart rate in the study group of massage
      therapy may imply an increased sensitivity to touch in the post-operative
      setting. Further research with larger study populations are needed to evaluate
      how and when massage therapy is useful for children with cerebral palsy.

PMID- 21742277
TI  - The impact of yoga upon female patients suffering from hypothyroidism.
AB  - OBJECTIVE: To study the effect of yoga on the quality of life of female
      hypothyroid patients. DESIGN: The WHO Quality of Life Scale(22) was used to
      assess the quality of life of 20 female hypothyroid patients. Subjects attended
      one hour yoga sessions daily for a period of one month. A pretest-post-test
      research design was used for data analysis. RESULTS: Patients' quality of life
      scores following the yoga program were greater than scores obtained prior to
      undertaking yoga (p < 0.01). Patients also reported significant improvement in
      their perception of the overall quality of life and of their health post yoga
      intervention. CONCLUSIONS: It can be concluded that yoga is valuable in helping
      the hypothyroid patients to manage their disease-related symptoms. Yoga may be
      considered as supportive or complementary therapy in conjunction with medical
      therapy for the treatment of hypothyroid disorder.

PMID- 21742278
TI  - Attitudes and views on chiropractic: a survey of United States midwives.
AB  - OBJECTIVE: A survey of midwives' knowledge and views about chiropractic. DESIGN:
      Cross-sectional descriptive survey. SETTING/LOCATION: An anonymous on-line self
      administered survey. PARTICIPANTS: United States midwives. OUTCOME MEASURE:
      Respondent demographics, professional training, personal and professional
      clinical experience, opinions on safety of chiropractic, and scope of
      chiropractic practice. RESULTS: A total of 187 midwife respondents completed the
      questionnaire resulting in a superficial response rate of 2.1%. Responders were
      certified nurse-midwives and had some form of training regarding chiropractic.
      The responders were aware that chiropractors worked with "birthing professionals"
      and attended to patients with both musculoskeletal and non-musculoskeletal
      disorders. A vast majority indicated a positive personal and professional
      clinical experience with chiropractic and that chiropractic was safe for pregnant
      patients and children. CONCLUSION: There is great awareness of and positive
      personal and professional experience with chiropractic on the part of midwives
      who participated in this survey. We encourage further research in this field.

PMID- 21742279
TI  - Tai Chi research review.
AB  - This review briefly summarizes recent Tai Chi research on physical benefits
      including balance and muscle strength and psychological benefits including
      attentiveness, sleep and anxiety. Cardiovascular changes following Tai Chi
      include decreased heart rate and blood pressure, increased vagal activity and
      decreased cholesterol. Pain syndromes that have been affected include
      fibromyalgia, osteoarthritis and rheumatoid arthritis. Autoimmune and immune
      conditions recently researched and reviewed here include osteoporosis, diabetes
      and HIV. Methodological problems with this research include the variability in
      forms (series of postures) used across studies as well as the intensity of the
      Tai Chi schedule. Further, most of the studies are based on within group changes
      rather than attention control group comparisons. Nonetheless, significant
      clinical improvements have been noted.

PMID- 21742280
TI  - Use of herbal drugs during pregnancy among 600 Norwegian women in relation to
      concurrent use of conventional drugs and pregnancy outcome.
AB  - PURPOSE: The purpose of this study was to investigate the use of herbal drugs by
      pregnant women in relation to concurrent use of conventional drugs, delivery, and
      pregnancy outcome. METHOD: 600 women at Stavanger University Hospital Norway were
      interviewed using a structured questionnaire within five days after delivery.
      Medical birth charts were reviewed with respect to pregnancy outcome. RESULTS: In
      all, 39.7% of the women reported having used herbal drugs during pregnancy, most
      commonly ginger, iron-rich herbs, echinacea and cranberry. Although 86.3% of the
      women reported having used conventional drugs during pregnancy there were few
      potential interactions between herbal drugs and conventional drugs. There was a
      significant association between the use of iron-rich herbs during pregnancy and
      high birthweight, and use of raspberry leaves and caesarean delivery. CONCLUSION:
      Use of herbal drugs is common during pregnancy and indicates a need for
      documentation about their safety in pregnancy.

PMID- 21742281
TI  - Traditional Chinese herbal medicine in the supportive management of patients with
      chronic cytopaenic marrow diseases -- a phase I/II clinical study.
AB  - We report on a phase I/II, single arm clinical trial studying the safety and
      efficacy of Traditional Chinese Medicine (TCM) in patients with various chronic
      cytopaenic marrow diseases including myelodysplastic syndrome (MDS),
      myelofibrosis (MF), aplastic anaemia (AA) and thalassemia intermedia, who either
      have failed, are unfit for or refused currently available Western medical
      treatment. Patients took oral herbal concoctions according to their TCM syndromes
      for 24 weeks while continuing with western medical management. The median age of
      this group of 31 patients was 61 (26--84) years old and median disease duration
      was 5 years (0.3--40 years). TCM herbs were well tolerated in these patients with
      multiple comorbidities and previous disease-related complications. Twenty-three
      patients completed the study with 5 (2 with MDS, 2 with MF and 1 with SAA)
      achieving some degree of haematological improvement. EORTC quality of life
      indicators improved in more than half of patients. This small study offers
      positive results and provides the basis for future larger studies which should
      randomize patients with MDS, MF and AA managed with standard Western medical
      treatment to without and with upfront combinations with TCM herbs. This will
      conclusively define the role of TCM in the supportive management of these
      diseases. This study was registered with Clinicaltrial.gov as NCT01224496.

PMID- 21742282
TI  - CAM: naturopathic dietary interventions for patients with type 2 diabetes.
AB  - OBJECTIVE: To test feasibility, acceptability, and preliminary effectiveness of a
      naturopathic dietary intervention in patients with Type 2 diabetes. METHODS:
      Prospective observational pilot study evaluating the change in clinical and
      patient-centered outcome measures following a 12-week individualized and group
      dietary education program delivered in naturopathic primary care. RESULTS: HbA1c
      improved in all participants (n = 12); mean - 0.4% +/- 0.49% SD, (p = 0.02).
      Adherence to healthful eating increased from 3.5 d/wk to 5.3 d/wk (p = 0.05).
      Specific nutritional behavior modification included: days/week consuming >=5
      servings of fruit/vegetables (p = 0.01), attention to fat intake (p = 0.05), and 
      11.3% carbohydrate reduction. Measures of physical activity, self-efficacy and
      self-management also improved significantly. CONCLUSION: A naturopathic dietary
      approach to diabetes appears to be feasible to implement among Type 2 diabetes
      patients. The intervention may also improve self-management, glycemic control,
      and have influences in other domains of self-care behaviors. Clinical trials
      evaluating naturopathic approaches to Type 2 diabetes are warranted.

PMID- 21742283
TI  - Effects of thermal therapy combining sauna therapy and underwater exercise in
      patients with fibromyalgia.
AB  - Fibromyalgia syndrome (FMS) is a chronic disorder that is characterized by
      widespread pain with localized tenderness. We aimed to investigate whether
      thermal therapy combining sauna therapy and underwater exercise improved pain,
      symptoms, and quality of life (QOL) in FMS patients. Forty-four female FMS
      patients who fulfilled the American College of Rheumatology (ACR) criteria
      received 12-week thermal therapy program comprising sauna therapy once daily for
      3 days/week and underwater exercise once daily for 2 days/week. Pain, symptoms,
      and QOL were assessed using a pain visual analog scale (VAS), a fibromyalgia
      impact questionnaire (FIQ), and a short form 36-item questionnaire (SF-36),
      respectively. All of the patients reported significant reductions in pain and
      symptoms of 31-77% after the 12-week thermal therapy program, which remained
      relatively stable (28-68%) during the 6-month follow-up period (that is, the
      thermal therapy program improved both the short-term and the long-term VAS and
      FIQ scores). Improvements were also observed in the SF-36 score. Thermal therapy
      combining sauna therapy and underwater exercise improved the QOL as well as the
      pain and symptoms of FMS patients.

PMID- 21742284
TI  - Effects of olive oil on striae gravidarum in the second trimester of pregnancy.
AB  - This study was performed in order to determine the effects of olive oil on striae
      gravidarum (SG) occurring within the second trimester of pregnancy. The
      intervention group, applied olive oil on their abdominal skin area twice a day
      until the end of the study term. The control group did not use any oil. Striae
      occurred in 40% of women using olive oil whilst striae were noted to occur in 50%
      of the control group. There was no significant difference between the
      intervention and control groups. This study notes that the use of olive oil to
      the end of the second trimester in pregnancy was not effective in reducing the
      occurrence of striae gravidarum.

PMID- 21742285
TI  - Anthroposophic health care in Sweden - a patient evaluation.
AB  - This study surveyed patients and their satisfaction with an integrative
      anthroposophic hospital. The patients were followed up by questionnaires up to
      six months after a stay in a Swedish clinic. Satisfaction with the care, life
      satisfaction, and health-related quality of life were measured for 53 patients,
      48 women, 5 men, with cancer, pain diseases, and psychosomatic problems. Sampling
      was consecutive and due to regional reasons. The evaluation of patients'
      satisfaction from the anthroposophic clinic (AC) was compared to similar
      questions of patients using conventional hospital care. The stay lasted 7-21 days
      and was paid by the patients' county councils. Causes for choosing AC were
      predominantly a positive attitude towards a holistic health view and expectations
      on being cared for. Less frequently noted was dissatisfaction with conventional
      care. Satisfaction with health care given after one month by the AC was sample
      scored more positively than the highest unit in the conventional clinic. This is
      important because women in conventional clinic report lower satisfaction. The AC
      sample consisted of 91% women with an average age of 54 years and a higher level
      of education compared to the sample from the conventional hospital. Health
      related quality of life and life satisfaction was, if not significant, moderately
      increased during the following six months. The AC initiated a new attitude and
      change in life habits that stimulated the patients into improving their life
      style habits and hence their overall health. Still challenging is the gender
      question. Why do middle-aged, well-educated women experience a need for and a
      satisfaction in complementary and integrative health care?

PMID- 21742286
TI  - Mongolian traditional style blood-letting therapy: a brief introduction.
AB  - Mongolian traditional style blood-letting therapy (MTSBLT) has been one of the
      most widely used traditional medicinal treatment modalities in Mongolia.
      Currently, the practice is widely used for hypertension, neck pain, headache,
      chronic hepatitis, ophthalmic or skin diseases and infectious diseases in
      Mongolia and China. Further studies concerning the mechanism and clinical
      application of the MTSBLT are needed for TCM practitioners to apply it in their
      own clinical practice and in order to expand the scope of TCM. MTSBLT is
      methodologically very different from the traditional Chinese-style blood-letting
      or wet-cupping. Although MTSBLT may be used as part of traditional Chinese
      medicine (TCM) treatment, this paper offers an introduction to MTSBLT.

PMID- 21742287
TI  - A comparative study of the experience of childbirth between women who preferred
      and had a caesarean section and women who preferred and had a vaginal birth.
AB  - OBJECTIVE: The aim of this study was to compare experiences and feelings during
      pregnancy and childbirth in women who preferred caesarean section during
      pregnancy and were delivered by a planned caesarean section, and women who
      preferred to give birth vaginally and actually had a spontaneous vaginal birth.
      DESIGN: Longitudinal cohort study where 693 women participated, 420 of whom were
      multiparas. METHODS: Data were collected from questionnaires distributed to women
      during pregnancy and two months postpartum in a Mid Sweden county. RESULTS: Women
      who preferred and actually were delivered by caesarean section experienced a fear
      of childbirth to a higher degree as compared to women with a vaginal birth.
      Despite a fulfilled request, women who had a caesarean section were not pleased
      with the decision making process. In addition, women who had a caesarean section
      on request were less satisfied with antenatal care and had a more negative birth
      experience, which made them doubt whether they would have more children.
      CONCLUSIONS: This study shows that a fulfilled request on mode of birth does not
      guarantee a positive birth experience. Antenatal information of all aspects of a
      caesarean section is vital for women who consider caesarean section where no
      medical indication is present. More research is needed about the decision making
      process regarding caesarean section on maternal request. Childbirth related fear
      is a common reason to request a caesarean birth. More knowledge about how women
      reason about caesarean section is required, and treatment related to fear of
      birth needs to be developed.

PMID- 21742288
TI  - Transfer in planned home births in Sweden--effects on the experience of birth: a
      nationwide population-based study.
AB  - OBJECTIVE: More than 10% of all planned home births in high-income countries are
      completed in the hospital. The aim of this study was to compare the birth
      experiences among women who planned to give birth at home and completed the birth
      at home and women who were transferred to hospital during or immediately after
      the birth. METHODS: All women in Sweden who had a planned home birth between 1998
      and 2005 (n=671) were invited to participate in the study. The women who agreed
      to participate received one questionnaire for each planned home birth. Mixed
      methods were used for the analysis. RESULTS: Women who had been transferred
      during or immediately after the planned home birth had a more negative birth
      experience in general. In comparison with women who completed the birth at home,
      the odds ratio for being less satisfied was 13.5, CI 8.1-22.3. Reasons for being
      dissatisfied related to organizational factors, the way the women were treated or
      personal ability. CONCLUSION: Being transferred during a planned home birth
      negatively affects the birth experience. Treatments as well as organizational
      factors are considered to be obstacles for a positive birth experience when
      transfer is needed. Established links between the home birth setting and the
      hospital might enhance the opportunity for a positive birth experience
      irrespective of where the birth is completed.

PMID- 21742289
TI  - Mothers' experiences of skin-to-skin care of healthy full-term newborns--a
      phenomenology study.
AB  - OBJECTIVES: Previous reports have shown that skin-to-skin contact immediately
      after birth is the optimal form of care for a full-term, healthy infant and its
      mother. As this is rarely researched the aim of this study was to explore
      experiences of skin-to-skin care in healthy mothers of healthy, full-term infants
      in the first days after birth. STUDY DESIGN: Using a lifeworld phenomenological
      approach, 20 women who had childbirth in hospital and were practising skin-to
      skin care were interviewed 1-2 weeks after birth. Analysis of all interview texts
      was directed towards discovering qualitative meanings through a process of
      identifying meaning units. These were then clustered and analysed with the aim of
      describing themes of meaning and the essence of the phenomenon. FINDINGS: The
      mothers wanted to give their newborn child the best possible care and the skin-to
      skin care started a positive spiral. A mutual interaction developed which acted
      as a generator releasing energy to the mother who wanted to continue the practice
      which in terms increased mother-infant affinity. Happiness, peace and
      satisfaction were expressed by the newborns; also a child who was crying or
      troublesome exhibited a positive response to skin-to-skin care. CONCLUSION: The
      study provides insight and knowledge which should guide attitudes and promote
      practices of this simple healthcare intervention; skin-to-skin contact care to
      healthy infants born at term. Healthcare professionals should support affinity
      between a mother and her newborn through facilitation and the provision of
      information about its benefits.

PMID- 21742290
TI  - Starting time for induction of labor and the risk for night-time delivery.
AB  - OBJECTIVE: To analyze if starting time for labor induction affected the risk of
      night-time delivery, and to evaluate to what extent the risk was influenced by
      Bishop score at start of induction, mode of induction, and parity. METHOD: A
      retrospective cohort study of women who delivered at Danderyd Hospital,
      Stockholm, Sweden, 2002-2006, comprising 1940 women induced by Dinoprostone
      (PGE(2)) or transcervical balloon catheter (BARD). Risks for night-time delivery
      were calculated as absolute risk and Odds Ratios by unconditional logistic
      regression using induction of labor in the morning as reference. RESULTS: For
      nulliparae with Bishop score 0-3 induced by BARD, odds ratios for night-time
      delivery were 0.42 (95% C.I. 0.19-0.93) and 0.09 (95% C.I. 0.02-0.47) when
      inductions started in the afternoon and evening, respectively, compared to
      inductions starting in the morning For multiparae, however, the risk of night
      time delivery was highest if induction started in the evening. Compared to
      inductions started in the morning, odds ratios for night-time delivery were 3.53
      (95% C.I. 2.57-4.83) and 8.49 (95% C.I. 4.45-16.19) for induction starting in the
      afternoon and evening, respectively. CONCLUSION: Starting time of labor induction
      affects the risk of giving birth at night. For nulliparae induced by BARD,
      starting the induction in the evening instead of during the day may reduce the
      number of night-time deliveries substantially. For multiparae, however, our data
      suggest that induction of labor should take place in the morning.

PMID- 21742291
TI  - Swedish adolescents' experiences of educational sessions at Youth Clinics.
AB  - Planning sex and relationship health education suitable for adolescents is a
      pedagogical challenge. OBJECTIVE: To describe how secondary school pupils in
      Sweden experience health educational sessions at Youth Clinics. METHODS: Data
      were collected from six focus groups within 2 weeks of an educational session.
      The groups consisted of pupils aged 14-16 years from three cities. The
      participants were 29 adolescents divided into groups of girls (n=15) and boys
      (n=14) and the interviews were audio taped. Data were analysed using qualitative
      content analysis. FINDINGS: Five categories were identified: Impact of the
      educational session, The desirable educator, Didactic setup, Gender inequalities
      and Suitable age for the educational session. The adolescents were satisfied with
      the content of the education and the session was evaluated as a complement to
      school education. The educators were seen as competent with an ability to create
      a comfortable atmosphere which made it easier for participants to discuss the
      subject and ask questions. The session was experienced as secure which was
      appropriate for the intimate and personal subject and gender aspects were seen as
      influencing the conversation. CONCLUSION: This study can give an understanding of
      the needs and demands of adolescents which can be useful when planning and
      conducting sex and relationship health education.

PMID- 21742292
TI  - Assessing compliance with a county board order for third trimester syphilis
      screening in Maricopa County, Arizona.
AB  - OBJECTIVES: Due to high rates of congenital syphilis, a Maricopa County board
      order was issued in 2003 to increase prenatal syphilis screening. The provisions
      of this order included prenatal syphilis screening during the first prenatal
      visit, to be repeated during the third trimester, and again at delivery. The
      purpose of the study was to evaluate syphilis screening practices and barriers to
      screening among obstetric providers. METHODS: Maricopa County medical providers
      who delivered at least 21 infants (97.2% of all deliveries) in 2008 according to
      live birth records were surveyed by telephone. RESULTS: A total of 146 surveys
      were completed representing 76% (319/421) of the delivering providers and 83% of
      delivered infants for 2008. All of the represented prenatal care providers
      reported testing their patients for syphilis at the first trimester, and 284
      (89%) reported screening again during the third trimester. CONCLUSIONS: All of
      the surveyed providers reported screening at least once for syphilis during
      pregnancy and most reported re-screening during the third trimester as
      recommended by the Maricopa County board order. Similar public health screening
      guidance should be considered in areas where congenital syphilis rates are high
      and/or where syphilis is prevalent among women of childbearing age. A local
      health order of this type is a simple intervention that can provide practice
      guidance on emerging health issues.

PMID- 21742293
TI  - Waiting for permission to enter the labour ward world: first time parents'
      experiences of the first encounter on a labour ward.
AB  - BACKGROUND: For women and their partners, the first meeting with professional
      staff on the labour ward is important. This initial encounter is a short but
      sensitive meeting. It may be particularly crucial for first time parents, most of
      whom have no prior experience of the birth environment. The objective of this
      study was to explore the meaning of first time mothers' and their partners' first
      encounter with midwives and other maternity care staff when they arrive on a
      hospital labour ward. METHOD: A hermeneutic, reflective lifeworld research
      approach was chosen to identify patterns of meanings, comprehension and
      explanations. Participants from Western Sweden were interviewed in the postnatal
      period; 37 individually, and 28 in focus groups. RESULTS: Four themes were
      identified: 'timing it right ', 'waiting to be informed', 'being in an inferior
      position', and 'facing reality with a mosaic of emotions'. The final
      interpretation of the phenomenon is captured as 'waiting for permission to enter
      the labour ward world'. CONCLUSION: The findings demonstrate the parents' efforts
      trying to determine the appropriateness of arrival to the labour ward. An
      asymmetric power relationship was expressed in the obedient acceptance of the
      waiting for attention in an unfamiliar situation. These findings suggest that the
      labour ward entry process is not parent centred. As entry to the labour ward sets
      the tone for the rest of the birth, this period in the labour process needs more
      attention in future research and practice from the maternity care professionals
      perspective.

PMID- 21742294
TI  - Parent-child communication for youth HIV prevention in Kenya: Letter to the
      Editor in response to "Voices unheard: youth and sexuality in the wake of HIV
      prevention in Kenya".

PMID- 21742295
TI  - First European Young Hepatologist Workshop: topics and advances.

PMID- 21742296
TI  - Liver fibrogenesis and metabolic factors.
AB  - Mechanisms of liver fibrosis are complex and varied. Among them, metabolic
      factors are particularly important in the development of fibrosis associated with
      nonalcoholic steatohepatitis (NASH). These factors are some of the "multiple
      parallel hits" responsible for liver damage during NASH. Nonalcoholic fatty liver
      disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Major
      profibrogenic protagonists, such as hepatic stellate cells and Kupffer cells, are
      activated by insulin resistance, apoptosis and local inflammation. Relations
      between steatosis, insulin resistance and fibrosis are complex. Initially, simple
      steatosis may be a way to store deleterious free fatty acid in neutral
      triglycerides. If the lipid storage threshold is exceeded, steatosis may become
      associated with lipotoxicity. Similarly, interindividual variations of adipose
      tissue expandability might explain various phenotypes, ranging from
      "metabolically obese patients with normal weight" to "metabolically normal
      morbidly obese patients". The metabolic abnormalities in subcutaneous and
      visceral adipose tissue are insulin resistance and low-grade inflammation, which
      are associated with increased release of free fatty acid flux and changes in
      adipocytokines production such as leptin, adiponectin and interleukin 6. The
      nuclear transcription factor peroxisome proliferator-activated receptor gamma
      (PPARgamma) and the endocannabinoid system might have important roles in liver
      fibrogenesis and are potential therapeutic targets. Finally, with the development
      of new molecular tools, gut microbiota has been recently identified for its
      pleiotropic functions, including metabolism regulation. Better knowledge of these
      mechanisms should lead to new strategies for the treatment of metabolic factors
      that play a key role in liver injuries.

PMID- 21742297
TI  - Contribution of biomarkers and imaging in the management of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most frequent malignant tumour of the
      liver. HCC prognosis is dependent on the determination of the tumour stage by
      conventional imaging and early screening. However, patient survival can vary with
      the same tumour stage. Biomarkers thus have a role in providing an earlier
      diagnosis, better prognosis classification before treatment and classification
      prognosis during treatment. In this review article, we will provide a successive,
      detailed description of the serum, pathological, molecular and imaging markers of
      HCC.

PMID- 21742298
TI  - Liver fibrogenesis and genetic factors.
AB  - Chronic liver diseases lead to the accumulation of fibrosis in the liver with
      eventual progression to cirrhosis and its complications. However, there is a wide
      range of inter-individual variation in the liver fibrogenesis process, thus
      posing a challenge to physicians to identify patients with poor prognosis. As
      demographic and environmental factors only account for a small portion of
      fibrogenesis variability, host genetic factors have been suggested as playing an
      important role. Due to technical limitations, the first genetic studies were
      restricted to the evaluation of candidate genes having a known or supposed
      function in liver fibrogenesis. Recently, technological improvements have made it
      possible to study the whole human genome in a single scan. Genome-wide
      association studies have considerably heightened the interest in genetics as part
      of the study of liver fibrogenesis through their identification of previously
      unsuspected genes that are statistically associated with liver fibrosis. It is
      thus possible to determine new diagnostic or prognostic genetic markers for the
      management of patients with chronic liver diseases. Moreover, functional analyses
      of these genes may provide new insights into the pathophysiology of liver
      fibrogenesis.

PMID- 21742299
TI  - Mechanisms of non-response to antiviral treatment in chronic hepatitis C.
AB  - Treatment of chronic hepatitis C virus (HCV) infection has substantially evolved
      over the past decade after the Consensus Conference organized by the European
      Association for the Study of the Liver in 1999. Since then, the standard of care
      (SOC) for patients with chronic hepatitis C has been the combination of pegylated
      interferon (pegIFN) alpha-2a or -2b and ribavirin. In patients infected with HCV
      genotype 1, by far the most frequent HCV genotype worldwide, such treatment leads
      to a cure of infection in only 40% to 50% of cases. Several factors have been
      identified to play a role in the outcome of therapy, including the treatment
      schedule, disease characteristics, viral, and host factors. Human genetic factors
      have been identified by a recent landmark discovery. However, these factors only
      partly explain the ability of IFN and ribavirin therapy to cure HCV infection.
      Several studies have demonstrated that, in non-responders, interferon-stimulated
      genes were up-regulated prior to therapy through unclear mechanisms. These
      findings, together with clinical, biochemical and histological data, may help
      better identify responders before starting therapy. This becomes particularly
      important as the standard treatment is physically and economically demanding. The
      future treatment of patients infected with HCV genotype 1 will be based on the
      combination of pegIFN and ribavirin with a protease inhibitor, telaprevir or
      boceprevir. Promising results of this triple combination in phase III clinical
      trials have been recently reported at the Liver Meeting 2010. With this therapy,
      higher cure rates will be achieved, but specific issues will be raised, such as
      the emergence of resistance to the protease inhibitors. The goal of this review
      is to discuss mechanisms involved in the non-response to current and future
      standard treatments.

PMID- 21742300
TI  - [Analysis of genetic polymorphism of the HLA-B and HLA-DR loci in patients with
      dermatophytic onychomycosis and in their first-degree relatives].
AB  - Onychomycosis is known to have predisposing factors and a high prevalence within
      families that cannot be explained by within-family transmission. We determined
      the frequency of HLA-B and HLA-DR haplotypes in 25 families of Mexican patients
      with onychomycosis in order to define the role of the class II major
      histocompatibility complex (MHC) in genetic susceptibility to this infection.
      Seventy-eight subjects participated in the study, 47 with onychomycosis and 31
      healthy individuals. The frequencies of the HLA-B and HLA-DR haplotypes were
      compared with those found in first-degree relatives without onychomycosis and in
      a historic control group of healthy individuals. The frequencies in the controls
      were similar to those of the healthy relatives of the patients. However, on
      comparison of the patients with historic controls, we detected a higher frequency
      of the HLA-DR8 haplotype (P=.03; odds ratio, 1.89; 95% confidence interval, 0.98
      36). These findings suggest that there are polymorphisms in genes of the MHC that
      increase susceptibility to onychomycosis, particularly haplotype HLA-DR8.

PMID- 21742301
TI  - [Intralesional infusion of methotrexate as neoadjuvant therapy improves the
      cosmetic and functional results of surgery to treat keratoacanthoma: results of a
      randomized trial].
AB  - BACKGROUND: Keratoacanthoma is currently considered to be an in situ squamous
      cell carcinoma that mainly affects patients over 70 years of age. The tumor has a
      good prognosis and, in some cases, can resolve spontaneously. Treatment involves
      simple excision. However, since the tumors generally occur on the face or
      extremities and display rapid growth, aggressive surgery may be required and the
      cosmetic results may be poor. OBJECTIVE: The primary study objective was
      assessment of the efficacy of presurgical intralesional methotrexate infiltration
      to reduce the size of the tumor and the corresponding surgical defect. MATERIAL
      AND METHODS: A prospective, randomized study was undertaken in patients with a
      diagnosis of keratoacanthoma of at least 1.5 cm who were seen in our service
      between January 2009 and January 2010. Two groups were established: one receiving
      a single infiltration of methotrexate prior to surgery and another that did not
      receive methotrexate. RESULTS: Of the 25 patients included in the study, 10
      received neoadjuvant intralesional methotrexate (group A) and 15 underwent
      surgery without prior infiltration of methotrexate (group B). The patients in
      group A displayed a reduction of between 50% and 80% in the size of the lesion
      prior to surgery. No complications were observed either in relation to
      methotrexate infusion or surgery. In group B, only 1 patient had a slight
      reduction in the dimensions of the lesion prior to surgery. In the remaining
      cases, the lesions remained similar (4 cases, 26%) or had increased in size (10
      cases, 66%) at the time of surgery. Five patients in this group required hospital
      admission following surgery. CONCLUSIONS: Neoadjuvant intralesional methotrexate
      is well tolerated and reduces the need for aggressive surgery in elderly patients
      with keratoacanthoma measuring more than 1.5 cm on the face or extremities.

PMID- 21742302
TI  - Diagnostic evaluation of type 2 (classic) choroidal neovascularization: optical
      coherence tomography, indocyanine green angiography, and fluorescein angiography.
AB  - PURPOSE: To evaluate the diagnostic characteristics of type 2 (classic) choroidal
      neovascularizations secondary to age-related macular degeneration using spectral
      domain-optical coherence tomography (SD OCT), indocyanine green angiography
      (ICGA), and fluorescein angiography (FA). DESIGN: Observational case series.
      METHODS:  SETTING: Institutional. STUDY POPULATION: Thirteen treatment-naive eyes
      with type 2 choroidal neovascularization without an occult component. MAIN
      OUTCOME MEASURES: Greatest horizontal dimension, based on the anatomic features
      of the neovascular complex by SD OCT (Spectralis; Heidelberg Engineering), ICGA,
      and FA; retinal leakage area in late-phase FA and ICGA; and the area of retinal
      edema in SD OCT. OBSERVATION PROCEDURES: For direct comparison, ICGA and FA
      images were overlaid manually on infrared plus SD OCT images using VirtualDub and
      Paint.NET software. Greatest horizontal dimension was measured using Image J
      software (National Institutes of Health). RESULTS: The mean greatest horizontal
      dimension of the neovascular complex and the retinal leakage area consistently
      were smaller on ICGA compared with the area of retinal edema on SD OCT. According
      to FA, the greatest horizontal dimension of early, well-demarcated
      hyperfluorescence was significantly smaller than the neovascular complex on SD
      OCT. In addition, the greatest horizontal dimension of the retinal leakage area
      in late-phase FA consistently was smaller than the area of retinal edema on SD
      OCT. CONCLUSIONS: In classic choroidal neovascularization, ICGA and FA seem to
      underestimate the extension of the neovascular complex and the associated retinal
      pathologic features compared with SD OCT imaging.

PMID- 21742303
TI  - A randomized pilot study of low-fluence photodynamic therapy versus intravitreal
      ranibizumab for chronic central serous chorioretinopathy.
AB  - PURPOSE: To report 6-month outcomes of a prospective, randomized study comparing
      the efficacy and safety between low-fluence photodynamic therapy (PDT) and
      intravitreal injections of ranibizumab in the treatment of chronic central serous
      chorioretinopathy. DESIGN: Prospective, randomized, single-center pilot study.
      METHODS: Sixteen eyes with chronic central serous chorioretinopathy were
      randomized to receive either low-fluence PDT or intravitreal injections of
      ranibizumab: 8 eyes in the low-fluence PDT group and 8 in the ranibizumab group.
      Rescue treatment was considered if subretinal fluid was sustained after
      completion of primary treatment: low-fluence PDT for the ranibizumab group and
      ranibizumab injection for the low-fluence PDT group. Main outcome measures were
      excess foveal thickness, resolution of subretinal fluid, choroidal perfusion on
      indocyanine green angiography, and best-corrected visual acuity. RESULTS: At 3
      months, the mean excess foveal thickness was reduced from 74.1 +/- 56.0 MUm to 
      35.4 +/- 44.5 MUm in the low-fluence PDT group (P = .017) and from 26.3 +/- 50.6
      MUm to -23.1 +/- 56.5 MUm in the ranibizumab group (P = .058). After a single
      session of PDT, 6 eyes (75%) in the low-fluence PDT group achieved complete
      resolution of subretinal fluid and reduction of choroidal hyperpermeability,
      whereas 2 (25%) eyes in the ranibizumab group achieved this after consecutive
      ranibizumab injections. Four eyes (50%) in the ranibizumab group underwent
      additional low-fluence PDT and accomplished complete resolution. At 3 months,
      significant improvement of best-corrected visual acuity was not demonstrated in
      the low-fluence PDT group (P = .075), whereas it was observed in the ranibizumab
      group (P = .012). However, the tendency toward improvement of best-corrected
      visual acuity was not maintained. CONCLUSIONS: In terms of anatomic outcomes, the
      effect of ranibizumab injections was not promising compared with that of low
      fluence PDT.

PMID- 21742305
TI  - The impact of physician subspecialty training, risk calculation, and patient age
      on treatment recommendations in ocular hypertension.
AB  - PURPOSE: To determine whether glaucoma subspecialty training, formal risk
      estimation, or patient age has an impact on physician treatment recommendations
      in cases of ocular hypertension. DESIGN: Experimental study. METHODS: Members of
      the American Academy of Ophthalmology (118) and American Glaucoma Society (58)
      were recruited. Each physician was first asked how many young and old patients
      with ocular hypertension he or she would treat to prevent someone from
      progressing to glaucoma (number needed to treat). The physicians then reviewed
      100 simulated cases of patients with ocular hypertension and reported their
      likelihood to treat each case. Half of these cases were presented with an
      estimated risk of conversion to glaucoma within 5 years and half were presented
      without an estimate. The treatment recommendations were analyzed to determine
      whether subspecialty status or the presence of a risk calculation had any impact
      on treatment recommendations. RESULTS: Both glaucoma specialists and non-glaucoma
      specialists were more likely to recommend treatment in cases for which a risk
      calculation was provided (P = .001). Furthermore, non-glaucoma specialists were
      more likely to recommend treatment for ocular hypertensive patients than were
      glaucoma specialists (P < .001). Finally, both groups indicated they were more
      likely to treat young patients than old. CONCLUSIONS: Both provision of a risk
      estimate and lack of glaucoma subspecialty training were associated with
      physicians being more likely to treat ocular hypertension. These findings have
      implications with regard to ways in which the treatment of ocular hypertensive
      patients could be modified and possibly made more consistent with available
      evidence.

PMID- 21742306
TI  - Postoperative conjunctival inflammation after pterygium surgery with amniotic
      membrane transplantation versus conjunctival autograft.
AB  - PURPOSE: To compare the postoperative conjunctival inflammation around the
      surgical site after pterygium surgery using either amniotic membrane
      transplantation (AMT) or free conjunctival autograft. DESIGN: Prospective,
      randomized, interventional study. METHODS: Forty-two eyes of 42 patients with
      primary pterygium underwent surgical excision followed by removal of
      subconjunctival fibrovascular tissue and intraoperative application of 0.02%
      mitomycin C. Then, the patients were randomized to receive either AMT (21 eyes)
      or free conjunctival autograft (21 eyes), with sutures used in both groups. Main
      outcome measures included presence of host conjunctival inflammation around the
      surgical site at 1 month after surgery and also recurrence of pterygium. RESULTS:
      Twelve-month follow-up was completed in 39 eyes of 39 patients (19 in the AMT
      group and 20 in the conjunctival autograft group). At 1 month after surgery,
      different grades of host conjunctival inflammation were present in 16 eyes
      (84.2%) in the AMT group and in 3 eyes (15%) in the conjunctival autograft group
      (P = .02). Subconjunctival injection of triamcinolone was performed in eyes with
      moderate or severe inflammation, which included 12 eyes (63.1%) in the AMT group
      and 2 eyes (10%) in the conjunctival autograft group (P < .001). Conjunctival
      recurrence of pterygium was seen in 2 eyes (10.5%) in the AMT group and in 2 eyes
      (10%) in the conjunctival autograft group (P = .92). After surgery, pyogenic
      granuloma developed in 3 eyes (15.8%) in the AMT group and in 1 eye (5%) in the
      conjunctival autograft group (P = .31). CONCLUSIONS: After pterygium surgery,
      conjunctival inflammation was significantly more common with AMT than with
      conjunctival autograft. However, with control of such inflammation and
      intraoperative application of mitomycin C, similar final outcomes were achieved
      with both techniques.

PMID- 21742307
TI  - Management of recurrent pterygium with intraoperative mitomycin C and
      conjunctival autograft with fibrin glue.
AB  - PURPOSE: To evaluate the safety and efficacy of using fibrin glue in cases of
      recurrent pterygium treated with pterygium excision and conjunctival autograft
      combined with mitomycin C. DESIGN: Retrospective, interventional case series.
      METHODS: The charts of 28 patients with recurrent pterygium who had undergone
      pterygium excision and conjunctival autograft using fibrin glue to secure the
      graft combined with intraoperative mitomycin C at a corneal service in a
      university teaching hospital were reviewed. Inclusion criteria were recurrent
      pterygium that had undergone at least 1 previous surgical excision and patients
      who had completed a regular postoperative follow-up of at least 12 months.
      Outcome measures included mean best-corrected visual acuity (BCVA) and
      intraoperative and postoperative complications. RESULTS: The mean age of the
      cohort was 49.7 years. There were no intraoperative complications. Early
      postoperative total graft dehiscence developed in 1 eye that underwent
      repositioning with glue and sutures. One eye had mild graft dehiscence and
      required no surgical intervention. One eye had a conjunctival cyst on the graft
      that did not require intervention. No significant change was observed in BCVA. At
      a mean follow-up of 26.5 months, there was 1 case of recurrence. CONCLUSIONS:
      Pterygium excision and conjunctival autograft using fibrin glue to secure the
      graft combined with intraoperative mitomycin C seems to be a safe and effective
      surgical option for treating recurrent pterygium. However, a larger cohort with
      longer follow-up may be required to assess the recurrence rate of this method.

PMID- 21742308
TI  - Corneal arcus is a sign of cardiovascular disease, even in low-risk persons.
AB  - PURPOSE: To examine the association of corneal arcus to cardiovascular disease
      (CVD) in an adult, ethnic Indian population. DESIGN: Population-based cross
      sectional study. METHODS: Population-based study of ethnic South Asian Indians 40
      to 80 years of age in Singapore from June 2007 through March 2009. We obtained a
      75.5% response rate (3397/4497). All participants underwent standardized
      interview and systemic and ocular examinations, followed by nonfasting blood
      sampling. Corneal arcus was detected using a standardized slit-lamp examination.
      The main outcome measure was CVD, defined from a self-reported history of
      previous myocardial infarction, angina, or stroke. RESULTS: Corneal arcus, found
      in 1701 (50.1%) of 3397 participants, was associated with older age (odds ratio
      [OR], 3.07; 95% CI, 2.78 to 3.40; P < .001), male gender (OR, 2.17; 95% CI, 1.81
      to 2.62; P < .001), higher levels of total cholesterol (OR, 1.14; 95% CI, 1.05 to
      1.24; P = .002), hypertension (OR, 1.14; 95% CI, 1.05 to 1.24; P = .013), and
      cigarette smoking (OR, 1.59; 95% CI, 1.25 to 2.03; P < .001). Corneal arcus was
      associated with CVD (OR, 1.31; 95% CI, 1.02 to 1.7; P = .0038) independent of the
      above-named cardiovascular risk factors. Participants with low-risk Framingham
      scores were more likely to be associated with CVD if they had corneal arcus (men:
      OR, 2.02; 95% CI, 1.20 to 3.40; P = .008; women: OR, 2.78; 95% CI, 1.36 to 3.01;
      P < .001). Corneal arcus was associated with CVD independent of the Framingham
      score (men: Akaike information criterion, 1524.39 for Framingham Score and
      corneal arcus vs 1527.38 for Framingham Score alone; women: 1000.14 vs 1003.54,
      respectively). CONCLUSIONS: Corneal arcus is associated with CVD, independent of
      risk factors in ethnic Indian adults, even in those at low risk for vascular
      disease.

PMID- 21742309
TI  - Does laser still have a role in the management of retinal vascular and
      neovascular diseases?
AB  - PURPOSE: To discuss the current role of laser therapies in the management of
      retinal vascular and neovascular diseases. DESIGN: Perspective. METHODS: Laser's
      role in the management of diabetic retinopathy, age-related macular degeneration,
      and venous occlusive disease is discussed, with emphasis on comparing laser with
      anti-vascular endothelial growth factor (VEGF) therapy and discussion of
      situations where these treatment methods can be complementary. RESULTS: Thermal
      panretinal photocoagulation remains the usual practice for treatment of
      neovascularization in proliferative diabetic retinopathy and after venous
      occlusive events. Focal/grid laser still has a role for patients with macular
      edema resulting from diabetes or venous occlusion that is poorly responsive to
      anti-VEGF agents and in patients who are unable or unwilling to return for
      frequent injections. Focal/grid laser also is used as combination therapy with
      anti-VEGF agents for these indications. Focal laser can be used for extrafoveal
      choroidal neovascularization to avoid the treatment burden and risks of multiple
      injections. Photodynamic therapy may be beneficial in the treatment of central
      serous chorioretinopathy and idiopathic polypoidal choroidal vasculopathy and as
      combination therapy with anti-VEGF agents in age-related macular degeneration.
      CONCLUSIONS: Anti-VEGF agents are effective in preventing vision loss and
      improving vision in multiple diseases, including diabetic retinopathy,
      neovascular age-related macular degeneration, and retinal vein occlusions.
      Despite a substantial decrease in its use for these conditions in recent years,
      laser therapies continue to serve important roles in our ability to combat
      retinal pathologic features and will remain a pivotal component of our practices
      for at least the next several years.

PMID- 21742304
TI  - Evaluation of the United States public health service guidelines for
      discontinuation of anticytomegalovirus therapy after immune recovery in patients
      with cytomegalovirus retinitis.
AB  - PURPOSE: To evaluate United States Public Health Service (USPHS) guidelines for
      discontinuing anticytomegalovirus (CMV) therapy in patients with AIDS who have
      immune recovery and quiescent retinitis after initiating highly active
      antiretroviral therapy. DESIGN: Cohort study of patients with CMV retinitis
      (Longitudinal Study of Ocular Complications of AIDS). METHODS: Participants had
      CMV retinitis and CD4+ T-cell counts of 50 cells/MUL or fewer enrolled from 1998
      through 2009 who demonstrated sustained immune recovery (2 consecutive CD4+ T
      cell counts of 100 cells/MUL or more at least 6 months apart) and inactive
      retinitis. Participants were classified into 2 groups according to anti-CMV
      treatment after immune recover: (1) continued anti-CMV therapy and (2)
      discontinued therapy. We evaluated survival, visual acuity, and CMV retinitis
      activity; we used propensity scores to adjust for confounding factors for these
      analyses. RESULTS: Of 152 participants reviewed, 71 demonstrated immune recovery,
      37 of whom discontinued therapy and 34 of whom continued therapy. At immune
      recovery, participants continuing therapy tended to be older (44 vs 40 years; P =
      .09), have bilateral retinitis (53% vs 32%; P = .10), and have lower CD4+ T-cell
      counts (148 vs 207 cells/MUL; P < .001). There were no statistical differences in
      any of the clinical outcomes (death, retinitis progress, visual acuity, or
      incidence of bilateral retinitis). Both groups lost visual acuity during follow
      up, on average 1.2 letters per year (P < .01). CONCLUSIONS: Discontinuation of
      anti-CMV therapy after immune recovery did not increase the risk of poor
      outcomes. These results support the current guidelines for discontinuation of
      anti-CMV therapy after achievement of sustained immune recovery.

PMID- 21742310
TI  - A novel conditioned nociceptive response in mice.
AB  - Chronic pain tends to be intractable, regardless of whether the etiology has
      improved or is persistent. This intractability may be due, in part, to
      conditioning factors, but studies of the underlying mechanism are limited. We
      predicted that the body might learn pain sensation during sustained pain. In the
      present study, we sought to examine the prediction that nociceptive pain could be
      a conditioned response. After pre-exposing mice to the context box, we assessed
      hind-paw licking responses(s), an unconditioned nociceptive response (UCR), in
      the training phase for 30 min following each of two injections (24h apart) of
      formalin into the hind paws. Forty-eight hours later, in the test phase, we
      tested for a conditioned nociceptive response (CR) from paw injections of saline,
      with mice placed in either the same or a different visual context box. The
      results showed that the CR elicited in the same context box was significantly
      larger than one elicited in the different box. An audiovisual context, which is
      used in prototypical Pavlovian conditioning, augmented the CR. The CR diminished
      to baseline levels during repeated extinction procedures, in which saline alone
      was given in the same context box. However, the CR in animals injected with
      saline in their home cages was unchanged. Treatment with scopolamine, which has
      an antimuscarinic action, and thus induces an amnestic effect, did not affect the
      UCR, but reduced the CR. These results indicated that repeated nociceptive
      stimuli were sufficient to produce a CR.

PMID- 21742311
TI  - Proliferation, migration and differentiation in juvenile and adult Xenopus laevis
      brains.
AB  - In contrast to mammals, the brain of adult non-mammalian vertebrates exhibits a
      higher proliferative and/or neurogenic activity. To provide new models on this
      issue, we have examined origin, distribution and fate of proliferating cells in
      the entire brain of juvenile and adult Xenopus laevis. Using immunohistochemistry
      for the Proliferation Cell Nuclear Antigen (PCNA), and/or the thymidine analog, 5
      Bromo-2' deoxyUridine (BrdU), the labeled cells are located in ventricular zones
      of the olfactory bulbs, cerebral hemispheres, preoptic region, ventral
      hypothalamus and cerebellum. Qualitatively, the highest level of proliferative
      cells was found in the telencephalic ventricles. By using in situ
      hybridization/immunocytochemistry double-labeling techniques, we demonstrate for
      the first time in post-metamorphic frog brain that the proliferative cells are
      localized in very close vivinity to the radial glial cells, progenitor cells that
      we have also identified in the ventricular layer using classical molecular
      markers (BLBP, Vimentin). In addition, after long post-BrdU administration
      survival times ranging between 14 and 28days, BrdU labeling combined with
      immunohistochemistry for markers of cell migration (DoubleCortin) or radial glial
      cells (BLBP), reveals that the proliferative cells are able to migrate from the
      ventricular zone into the brain parenchyma, most likely by migrating along the
      radial processes. Finally, at survival time of 28days and by using a combination
      of BrdU labeling and in situ hybridization for markers of differentiation states
      (Neuro-beta-tubulin, Proteolipid Protein), we demonstrate that newborn cells can
      differentiate in large portion into either neurons or oligodendrocytes.

PMID- 21742312
TI  - Neurogenesis in Huntington's disease: can studying adult neurogenesis lead to the
      development of new therapeutic strategies?
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by an unstable expansion of CAG repeats in the HD gene. The symptoms
      include cognitive dysfunction and severe motor impairments. The neuropathology is
      characterized by neuronal loss mainly in the striatum and cortex, although other
      regions including the hippocampus are also affected. In this review we discuss
      the different mouse models of HD, and how the process of neurogenesis in the
      dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) is
      affected in each. Deficits in adult hippocampal neurogenesis have been repeatedly
      shown in different genetic models of HD, raising the possibility that an
      impairment of the neurogenic process might underlie some of the cognitive
      deficits associated with this neurodegenerative disorder. On the other hand, an
      increase in SVZ neurogenesis has been observed in human HD brains while no
      differences in SVZ cell proliferation have been detected in the mouse models. In
      this review we will discuss the discrepancies between these findings as well as
      the several mechanisms that might contribute to a dysregulation of adult
      neurogenesis in HD. Finally, we will provide an overview of the various
      therapeutic strategies aimed at stimulating the endogenous neurogenic capacity
      that have been tested in HD genetic models. Ultimately, the insights obtained
      from these and future studies will greatly improve our understanding of the
      cognitive impairment characteristic of HD.

PMID- 21742313
TI  - Highly diastereoselective conjugate addition of nitroalkanes to alpha,beta
      unsaturated sugar lactones for the efficient synthesis of chiral 2-pyrrolidones.
AB  - A series of 4,5-substituted chiral gamma-lactams were synthesized through a
      highly diastereoselective addition-rearrangement approach from 2,3-unsaturated
      sugar lactones. The single-crystal X-ray structure of one product indicated that
      the sugar ring was attacked from the axial side. Partial reduction of the nitro
      group produced N-hydroxy-gamma-lactams, which were further reduced with TiCl(3)
      to yield the 4,5-substituted chiral gamma-lactams. The absolute configuration of
      C5 of the gamma-lactam was determined by NOESY spectra.

PMID- 21742314
TI  - Ozonolysis of the double bond of the unsaturated uronate residue in low-molecular
      weight heparin and K5 heparosan.
AB  - Ozone is known to add across and cleave carbon-carbon double bonds. Ozonolysis is
      widely used for the preparation of pharmaceuticals, for bleaching substances and
      for killing microorganisms in air and water sources. Some polysaccharides and
      oligosaccharides, such as those prepared using chemical or enzymatic beta
      elimination, contain a site of unsaturation. We examined ozonolysis of low
      molecular-weight heparins (LMWHs), enoxaparin and logiparin, and heparosan oligo-
      and polysaccharides for the removal of the nonreducing terminal unsaturated
      uronate residue. 1D (1)H NMR showed that these ozone-treated polysaccharides
      retained the same structure as the starting polysaccharide, except that the C4-C5
      double bond in the nonreducing end unsaturated uronate had been removed. The
      anticoagulant activity of the resulting product from enoxaparin and logiparin was
      comparable to that of the starting material. These results demonstrate that
      ozonolysis is an important tool for the removal of unsaturated uronate residues
      from LMWHs and heparosan without modification of the core polysaccharide
      structure or diminution of anticoagulant activity. This reaction also has
      potential applications in the chemoenzymatic synthesis of bioengineered heparin
      from Escherichia coli-derived K5 heparosan.

PMID- 21742315
TI  - Structural characterization and study of immunoenhancing properties of
      heteroglycan isolated from a somatic hybrid mushroom (PfloVv1aFB) of Pleurotus
      florida and Volvariella volvacea.
AB  - A water soluble polysaccharide isolated from the hot aqueous extract of the fruit
      bodies of the somatic hybrid mushroom (PfloVv1aFB), raised through protoplast
      fusion between the strains of Pleurotus florida and Volvariella volvacea was
      found to consist of d-glucose, d-galactose, and d-mannose in a molar ratio of
      nearly 4:1:1 and showed macrophage, splenocyte, and thymocyte activation. On the
      basis of sugar analysis, methylation analysis, periodate oxidation, and NMR
      studies ((1)H, (13)C, DEPT-135, DQF-COSY, TOCSY, NOESY, ROESY, HMQC and HMBC),
      the structure of the repeating unit of the polysaccharide was established as:
      [structure: see text].

PMID- 21742316
TI  - Synthesis of cellulose dehydroabietate in ionic liquid [bmim]Br.
AB  - A new type of cellulose derivative, cellulose dehydroabietate (CDA), was
      synthesized by the O-acylation reaction of cellulose with dehydroabietic acid
      chloride (DHAC) using ionic liquid 1-butyl-3-methylimidazolium bromide ([bmim]Br)
      as a solvent and 4-dimethyl-aminopyridine (DMAP) as a catalyst. The resulting CDA
      was characterized by means of FT-IR, X-ray diffraction (XRD), scanning electron
      microscopy (SEM), thermal gravimetric analysis (TGA), and elemental analysis.
      Also, some properties of CDA were determined. These results showed that CDA has
      better solubility, water-repellency, and resistance to acids and bases than raw
      cellulose, and these properties increase with the DS of CDA.

PMID- 21742317
TI  - One-step synthesis of glucose-branched galactomannan.
AB  - The synthesis of branched polysaccharides using naturally occurring materials has
      been reported since 1975, but applications of branched polysaccharides are
      relatively limited because of the long and complex modification processes. In
      this work, a practical and efficient procedure is presented that in one step
      levoglucosan can be grafted to galactomannan (at 115 degrees C for 15h) with
      monochloroacetic acid as catalyst. The structural characteristics of the
      resulting substances were investigated by NMR spectroscopy. The MS (molar degree
      of substitution) of glucose was shown to gradually increase with the increase of
      the ratio of levoglucosan to galactomannan, and the maximal MS is 0.6.
      Levoglucosan units are mostly grafted to the C6-OH of the galactosyl residues in
      galactomannan, and the maximal percentage of the substituted C6-OH of galactosyl
      residues is 42.2%. The resulting levoglucosan tended to graft to the branching
      glucosyl residues of copolymers with an increase in MS, and the average length of
      the branching glucose is 3.6 when MS is 0.6.

PMID- 21742318
TI  - The effect of synthesis media on the properties of substituted
      polyaniline/chitosan composites.
AB  - Substituted polyaniline/chitosan (sPANI/Ch) composites were chemically
      synthesized in H(2)SO(4) and CH(3)COOH synthesis media. Structural and physical
      properties of the composites were characterized by using FTIR, SEM, TGA, UV-vis,
      XRD techniques, and conductivity measurements. The effect of synthesis media on
      morphology, thermal stability, conductivity, and crystalline properties was
      investigated. Chemical interactions between substituted polyanilines and chitosan
      were explained using FTIR spectra results. The different morphological surfaces
      were observed in SEM images of the composites. The size of the substituted
      polyaniline/chitosan (sPANI/Ch) composites was in nanoscale, and the composites
      synthesized in acetic acid media showed smaller structures than those of
      H(2)SO(4) media and pure chitosan. It was interpreted from XRD results that the
      composites have amorphous structure and the PNEANI/Ch-CH(3)COOH composite has the
      highest crystallinity.

PMID- 21742319
TI  - Multiple pulmonary arteriolar emboli in a patient with disseminated mucormycosis
      and myelodysplastic syndrome.

PMID- 21742320
TI  - Deep and surface hemodynamic signal from functional time resolved transcranial
      near infrared spectroscopy compared to skin flowmotion.
AB  - The potential disturbance in the prefrontal cortex hemodynamic signal measured by
      functional near infrared spectroscopy (NIRS), due to forehead skin flowmotion,
      detected by laser Doppler flowmetry, was investigated by a standard protocol of
      hemodynamic challenge by Valsalva maneuver, aimed at assessing and disentangling
      local regulatory responses in skin vasomotion and in cerebral perfusion in
      presence of a strong systemic drive, and to quantify the common information in
      the two signals. The deep cortical NIRS signal did not appear to be affected by
      surface vasomotor activity, and autoregulation dynamics were dominant with
      respect to autonomic control of circulation.

PMID- 21742321
TI  - A comparison of multivariate causality based measures of effective connectivity.
AB  - During the past several years a variety of methods have been developed to
      estimate the effective connectivity of neural networks from measurements of brain
      activity in an attempt to study causal interactions among distinct brain areas.
      Understanding the relative strengths and weaknesses of these methods, the
      assumptions they rely on, the accuracy they provide, and the computation time
      they require is of paramount importance in selecting the optimal method for a
      particular experimental task and for interpreting the results obtained. In this
      paper, the accuracy of the six most commonly used techniques for calculating
      effective connectivity are compared, namely directed transfer function, partial
      directed coherence, squared partial directed coherence, full frequency directed
      transfer function, direct directed transfer function, and Granger causality.
      These measures are derived from the coefficients and error terms of
      autoregressive models calculated using the dynamic autoregressive neuromagnetic
      causal imaging (DANCI) algorithm. These techniques were evaluated using
      magnetoencephalography recordings as well as several synthetic datasets that
      simulate neurophysiological signals, which varied on several parameters,
      including network size, signal-to-noise ratio, and network complexity, etc. The
      results show that Granger causality is the most accurate method across all
      experimental conditions explored and suggest that large multisensor data sets can
      be accurately analyzed using Granger causality with the DANCI algorithm.

PMID- 21742322
TI  - A DIAMOND method of inducing classification rules for biological data.
AB  - Identifying the classification rules for patients, based on a given dataset, is
      an important role in medical tasks. For example, the rules for estimating the
      likelihood of survival for patients undergoing breast cancer surgery are critical
      in treatment planning. Many well-known classification methods (as decision tree
      methods and hyper-plane methods) assume that classes can be separated by a linear
      function. However, these methods suffer when the boundaries between the classes
      are non-linear. This study presents a novel method, called DIAMOND, to induce
      classification rules from datasets containing non-linear interactions between the
      input data and the classes to be predicted. Given a set of objects with some
      classes, DIAMOND separates the objects into different cubes, and assigns each
      cube to a class. Via the unions of these cubes, DIAMOND uses mixed-integer
      programs to induce classification rules with better rates of accuracy, support
      and compact. This study uses three practical datasets (Iris flower, HSV patients,
      and breast cancer patients) to illustrate the advantages of DIAMOND over some
      current methods.

PMID- 21742325
TI  - Human chorionic gonadotropin from day 2 spent embryo culture media and its
      relationship to embryo development.
AB  - OBJECTIVE: To detect hCG in spent embryo culture media at day 2 after
      intracytoplasmic sperm injection and to assess the relationship of hCG to embryo
      development. DESIGN: Experimental study. SETTING: Fertility center and clinical
      diagnostic laboratory. SAMPLE(S): A total of 102 spent culture media from day 2
      human embryos and corresponding unexposed media for blank control.
      INTERVENTION(S): The culture media samples were tested for hCG by ELISA. MAIN
      OUTCOME MEASURE(S): Quantity of hCG produced by embryos and correlation with the
      embryos' developmental status. RESULT(S): hCG was found in 93 of 102 culture
      media tested by enzyme-linked immunosorbent assay. The correlation analysis
      revealed that the concentration of hCG was independent of embryo developmental
      status. CONCLUSION(S): The ability to detect hCG from day 2 spent culture media
      may be used as a marker for embryo competence.

PMID- 21742324
TI  - Genome-wide identification of Chlamydia trachomatis antigens associated with
      tubal factor infertility.
AB  - OBJECTIVE: To identify Chlamydia trachomatis antigens that can be used to
      differentially diagnose tubal factor infertility in comparison with previously
      reported heat shock protein 60. DESIGN: In vitro study. SETTING: Academic medical
      center. PATIENT(S): Infertile women with and without tubal pathology diagnosed
      laparoscopically. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Antibody
      responses to C. trachomatis in infertile women with or without tubal pathologies
      using a C. trachomatis genome-wide proteome array. RESULT(S): Comparison of the
      antibody profiles revealed 30 C. trachomatis antigens that were preferentially
      recognized in women with tubal factor infertility, with a detection sensitivity
      and specificity of 80.6% and 56.5%, respectively, 10 of which showed 100%
      specificity. A combination of CT443 and CT381 antigens yielded the highest
      detection sensitivity (67.7%) while maintaining 100% specificity. CONCLUSION(S):
      These findings have demonstrated that antibodies to CT443 and CT381, when used in
      combination, have higher sensitivity and specificity in predicting tubal factor
      infertility than other indicators for tubal factor infertility, such as heat
      shock protein 60 antibodies (35.5%, 100%) or hysterosalpingogram (65%, 83%).
      Using a panel of C. trachomatis antigens to serologically diagnose tubal factor
      infertility can save the patients from undertaking expensive and invasive
      procedures for determining tubal pathology and choosing treatment plans.

PMID- 21742326
TI  - Thyroid function during ovarian stimulation: a systematic review.
AB  - OBJECTIVE: To review the evidence regarding thyroid function and thyroid
      autoimmunity (TAI) changes in women undergoing ovarian stimulation (OS). DESIGN:
      Studies eligible for the systematic review were those that reported data on
      thyroid function or TAI both before and during OS or within 1 month after OS.
      SETTING: Academic hospital. PATIENT(S): Women with abnormal thyroid function or
      TAI (n = 419) and controls (n = 425). INTERVENTION(S): Ovarian stimulation. MAIN
      OUTCOME MEASURE(S): Serum TSH, free thyroxine, free tri-iodothyronine and thyroid
      antibodies. RESULT(S): Seven studies, between 2000 and 2011, were included. Serum
      TSH concentrations were significantly increased in three studies and were not
      changed in two studies. Serum free thyroxine concentrations were increased in two
      studies, were not changed in one, and were decreased in another. Serum free tri
      iodothyronine concentrations were not changed in the only study in which they
      were measured. Thyroid antibody concentrations were decreased in one study and
      were not changed in two studies, even in the presence of changes in thyroid
      function. CONCLUSION(S): The current evidence is inconclusive regarding OS effect
      on thyroid function or TAI. Serum TSH concentrations may be increased during or
      within 1 month after OS, exceeding the threshold of 2.5 mU/L suggested for the
      first trimester of pregnancy, but further prospective studies are needed to
      provide conclusive evidence for or against universal evaluation of thyroid
      function and TAI in women undergoing OS.

PMID- 21742327
TI  - How bone forms in large cancellous defects: critical analysis based on
      experimental work and literature.
AB  - The behaviour of physiological biomaterials, beta-tricalciumphosphate and
      hydroxyapatite, is analysed based on current literature and our own experimental
      work. The properties of graft substitutes based on ceramic materials are clearly
      defined according to their scientific efficiency. The strength of the materials
      and their biodegradability are still not fully evaluated. Strength and
      degradability have a direct proportional relationship and are considered the most
      efficient way to be adapted by their properties to the needs for the treatment of
      bone defects. New technologies for the manufacturing process are presented that
      increase those properties and thus open up new indications and easier application
      of the ceramic materials. The implantation process as well is carefully validated
      by animal experiments to avoid failures. Based on the experiments, a completely
      new approach is defined as to how primary bone formation with osteoconductive
      ceramics can be achieved. The milestones in that approach comprise a
      synthetically manufactured replica of the bone marrow spaces as osteoconductive
      ladder, whereas the bead is defined as bone-forming element. As a result,
      materials are available with high strength if the ceramic is solid or highly
      porous and possesses a micro-structure. The injection moulding process allows for
      the combination of high strength of the material with high porosity. Based on the
      strong capillary forces, micro-chambered beads fulfil most expectations for
      primary bone formation in cancellous bone defects, including drug delivery,
      mechanical strengthening if necessary, and stable implantation in situ by
      coagulation of the blood and bone marrow suctioned in.

PMID- 21742328
TI  - Management of blunt renal injury in a level 1 trauma centre in view of the
      European guidelines.
AB  - BACKGROUND: Debate continues about the optimal management strategy for patients
      with renal injury. PURPOSE: To report the diagnostics and treatment applied in a
      level 1 trauma centre and to compare it to the recommendations of the European
      Association of Urology guidelines concerning blunt renal injury. METHODS: The
      management of all patients with blunt renal injury, admitted to the level 1
      trauma centre of the Academic Medical Centre, between January 2005 and December
      2009 was reviewed retrospectively. RESULTS: Median age and ISS of the 186
      included patients were 40 and 17 years respectively. All but one haemodynamically
      stable patients with microscopic haematuria received nonoperative management.
      Sixty percent of the haemodynamically stable patients with gross haematuria
      underwent CT scanning. Patients with grade 1-4 renal injury received nonoperative
      management. Additionally, two patients with grade 3-4 renal injury received
      angiography and embolization (A&E). One patient with grade 5 injury underwent
      renal exploration and two A&E. Seven of the 8 haemodynamically unstable patients
      underwent emergency laparotomy and in 2 patients, haemodynamically unstable
      because of renal injury, A&E was performed as an adjunct to surgical
      intervention. CONCLUSIONS: In the present study, violation of the guidelines
      increased with injury severity. A&E can provide both a useful adjunct to
      nonoperative management and alternative to surgical intervention in specialised
      centres with appropriate equipment and expertise, even in patients with high
      grade renal injury. We advocate an update of the guidelines with a more prominent
      role of A&E.

PMID- 21742330
TI  - Can Forkhead Box P1 be a novel therapeutic target for atherosclerosis?

PMID- 21742331
TI  - An open source lower limb model: Hip joint validation.
AB  - Musculoskeletal lower limb models have been shown to be able to predict hip
      contact forces (HCFs) that are comparable to in vivo measurements obtained from
      instrumented prostheses. However, the muscle recruitment predicted by these
      models does not necessarily compare well to measured electromyographic (EMG)
      signals. In order to verify if it is possible to accurately estimate HCFs from
      muscle force patterns consistent with EMG measurements, a lower limb model based
      on a published anatomical dataset (Klein Horsman et al., 2007. Clinical
      Biomechanics. 22, 239-247) has been implemented in the open source software
      OpenSim. A cycle-to-cycle hip joint validation was conducted against HCFs
      recorded during gait and stair climbing trials of four arthroplasty patients
      (Bergmann et al., 2001. Journal of Biomechanics. 34, 859-871). Hip joint muscle
      tensions were estimated by minimizing a polynomial function of the muscle forces.
      The resulting muscle activation patterns obtained by assessing multiple powers of
      the objective function were compared against EMG profiles from the literature.
      Calculated HCFs denoted a tendency to monotonically increase their magnitude when
      raising the power of the objective function; the best estimation obtained from
      muscle forces consistent with experimental EMG profiles was found when a
      quadratic objective function was minimized (average overestimation at
      experimental peak frame: 10.1% for walking, 7.8% for stair climbing). The lower
      limb model can produce appropriate balanced sets of muscle forces and joint
      contact forces that can be used in a range of applications requiring accurate
      quantification of both. The developed model is available at the website
      https://simtk.org/home/low_limb_london.

PMID- 21742332
TI  - Comparison of hexahedral and tetrahedral elements in finite element analysis of
      the foot and footwear.
AB  - Finite element analysis has been widely used in the field of foot and footwear
      biomechanics to determine plantar pressures as well as stresses and strains
      within soft tissue and footwear materials. When dealing with anatomical
      structures such as the foot, hexahedral mesh generation accounts for most of the
      model development time due to geometric complexities imposed by branching and
      embedded structures. Tetrahedral meshing, which can be more easily automated, has
      been the approach of choice to date in foot and footwear biomechanics. Here we
      use the nonlinear finite element program Abaqus (Simulia, Providence, RI) to
      examine the advantages and disadvantages of tetrahedral and hexahedral elements
      under compression and shear loading, material incompressibility, and frictional
      contact conditions, which are commonly seen in foot and footwear biomechanics.
      This study demonstrated that for a range of simulation conditions, hybrid
      hexahedral elements (Abaqus C3D8H) consistently performed well while hybrid
      linear tetrahedral elements (Abaqus C3D4H) performed poorly. On the other hand,
      enhanced quadratic tetrahedral elements with improved stress visualization
      (Abaqus C3D10I) performed as well as the hybrid hexahedral elements in terms of
      contact pressure and contact shear stress predictions. Although the enhanced
      quadratic tetrahedral element simulations were computationally expensive compared
      to hexahedral element simulations in both barefoot and footwear conditions, the
      enhanced quadratic tetrahedral element formulation seems to be very promising for
      foot and footwear applications as a result of decreased labor and expedited model
      development, all related to facilitated mesh generation.

PMID- 21742333
TI  - Determination of organochlorine pesticide residues in fatty foods: a critical
      review on the analytical methods and their testing capabilities.
AB  - Organochlorine pesticide (OCP) residues in foods have been of concern for several
      decades. However, the analysis of some of the OCPs and their metabolites or
      derivatives, such as endrin aldehyde, endrin ketone, nonachlor, etc. in fatty
      foods (including foods of animal and plant origin), was not commonly included in
      routine monitoring programme. Recently, the Stockholm Convention introduced nine
      plus one new persistent organic pollutants (POPs) that included chlordecone and
      some other OCPs. Is there a method available that can analyze both traditional
      OCPs, together with their metabolites and derivatives in fatty foods?
      Furthermore, is there a suitable method that can monitor OCPs and the newly added
      POPs including chlordecone in fatty foods together in a pot? This review aims to
      provide some background information to answer these questions.

PMID- 21742334
TI  - Retention times and bandwidths in reversed-phase gradient liquid chromatography
      of peptides and proteins.
AB  - Due to dramatic effects of even small changes in mobile phase composition on the
      retention, separations of high-molecular compounds are very difficult, if
      possible at all, at isocratic conditions and need gradient elution. The theory of
      gradient elution for small molecules is well established, however its
      applications to reversed-phase gradient separations of biopolymers are not
      straightforward because of specific problems, such as slow diffusion, limited
      accessibility of the stationary phase for larger molecules, or possible sample
      conformation changes during the elution. Theoretical prediction of gradient data
      needs the parameters of model retention equations to be known, which however
      cannot be determined at isocratic conditions. The present work overviews the
      attempts at implementation of the conventional gradient theory developed for low
      molecular compounds to the description and prediction of gradient separations of
      peptides and proteins on various types of HPLC columns: conventional analytical
      columns packed with wide-pore fully porous, fused-core superficially porous and
      non-porous particles; silica-based monolithic columns and organic-polymer
      poly(alkylmethacrylate) and poly(styrene-divinylbenzene) monolithic columns in
      capillary and disc formats. The attention is focused on the determination of the
      parameters necessary to predict gradient retention times (volumes) and bandwidths
      using the theoretical model equations. The accuracy of the prediction of protein
      retention on totally porous columns improves if size exclusion effect is taken
      into account, but this is not necessary with non-porous or superficially porous
      particles. Band dispersion effects counteracting band compression in gradient
      elution depend on the type of column, on the protein and on the gradient volume
      (steepness) and complicate the prediction of band broadening in gradient
      chromatography of proteins, however the conventional gradient model can be
      employed to estimate the effects of changing gradient parameters on the
      bandwidths, as well as on the elution times (volumes) of proteins.

PMID- 21742335
TI  - Tracking juniper berry content in oils and distillates by spectral deconvolution
      of gas chromatography/mass spectrometry data.
AB  - The complex nature of botanicals and essential oils makes it difficult to
      identify all of the constituents by gas chromatography/mass spectrometry (GC/MS)
      alone. In this paper, automated sequential, multidimensional gas
      chromatography/mass spectrometry (GC-GC/MS) was used to obtain a matrix-specific,
      retention time/mass spectrometry library of 190 juniper berry oil compounds.
      GC/MS analysis on stationary phases with different polarities confirmed the
      identities of each compound when spectral deconvolution software was used to
      analyze the oil. Also analyzed were distillates of juniper berry and its oil as
      well as gin from four different manufacturers. Findings showed the chemical
      content of juniper berry can be traced from starting material to final product
      and can be used to authenticate and differentiate brands.

PMID- 21742336
TI  - An improved capillary model for describing the microstructure characteristics,
      fluid hydrodynamics and breakthrough performance of proteins in cryogel beds.
AB  - A capillary-based model modified for characterization of monolithic cryogels is
      presented with key parameters like the pore size distribution, the tortuosity and
      the skeleton thickness employed for describing the porous structure
      characteristics of a cryogel matrix. Laminar flow, liquid dispersion and mass
      transfer in each capillary are considered and the model is solved numerically by
      the finite difference method. As examples, two poly(hydroxyethyl methacrylate)
      (pHEMA) based cryogel beds have been prepared by radical cryo-copolymerization of
      monomers and used to test the model. The axial dispersion behaviors, the pressure
      drop vs. flow rate performance as well as the non-adsorption breakthrough curves
      of different proteins, i.e., lysozyme, bovine serum albumin (BSA) and
      concanavalin A (Con A), at various flow velocities in the cryogel beds are
      measured experimentally. The lumped parameters in the model are determined by
      matching the model prediction with the experimental data. The results showed that
      for a given cryogel column, by using the model based on the physical properties
      of the cryogel (i.e., diameter, length, porosity, and permeability) together with
      the protein breakthrough curves one can obtain a reasonable estimate and detailed
      characterization of the porous structure properties of cryogel matrix,
      particularly regarding the number of capillaries, the capillary tortuousness, the
      pore size distribution and the skeleton thickness. The model is also effective
      with regards to predicting the flow performance and the non-adsorption
      breakthrough profiles of proteins at different flow velocities. It is thus
      expected to be applicable for characterizing the properties of cryogels and
      predicting the chromatographic performance under a given set of operating
      conditions.

PMID- 21742337
TI  - Modifying conventional high-performance liquid chromatography systems to achieve
      fast separations with Fused-Core columns: a case study.
AB  - The theoretical increase in performance from the use of high efficiency columns
      with conventional HPLC equipment is generally not observed due to the design
      limitations of such equipment, particularly with respect to extra-column
      dispersion (ECD). This study examines the impact of ECD from a Waters Alliance
      2695 system on the performance of 2.7 MUm HALO C(18) Fused-Core superficially
      porous particle columns of various dimensions. The Alliance system was re
      configured in different ways to reduce extra-column volume (ECV) and the ECD
      determined in each case as a function of flow rate up to a maximum of 2 mL/min.
      The results obtained showed a progressive decrease in ECD as the ECV was reduced,
      irrespective of the flow rate employed. However, this decrease in ECD was less
      than theoretically expected for the lower ECV configurations. The inability to
      reduce the actual extra-column dispersion further was attributed to additional
      dispersion associated with the design/volume of the auto-injector. This was
      confirmed by making sample injections with a low dispersion manual injection
      valve, instead of auto-injection, for the two lowest ECV configurations studied.
      In each case, the measured and predicted ECD values were in good agreement. The
      auto-injector module is an integral part of the Alliance 2695 instrument and
      cannot be easily modified. However, even with autosampler injection, for a 3mm ID
      * 100 mm Fused-Core column approximately 70% of the maximum plate count (~84% of
      the resolution or more) could still be obtained in isocratic separations for
      solutes with k >= ~4.5 when using the lowest ECV configuration. This study also
      highlights some of the problems inherent in trying to measure accurately the true
      extra-column dispersion of a chromatographic system and compares the results
      obtained to those theoretically predicted. Using this same lowest volume
      instrument configuration, two real-world pharmaceutical methods were scaled to
      separations that are ~3-3.5-fold faster, while still maintaining comparable data
      quality (resolution and signal-to-noise ratios).

PMID- 21742338
TI  - Metrics of separation performance in chromatography. Part 1. Definitions and
      application to static analyses.
AB  - Earlier introduced metrics of separation performance are described in a
      systematic way. After providing the definitions of the metrics suitable for a
      broad variety of applications, the study focuses on static analyses (isothermal
      GC, isocratic LC, etc.) and their general separation performance. Statistically
      expected number of resolved (adequately separated) single-component peaks is
      treated as the ultimate metric of general separation performance of
      chromatographic analysis. That number depends on the peak capacity of the
      analysis and the number of components in a test mixture. The peak capacity, in
      turn, depends on the separation capacity of a column and the lowest separation
      required by the data-analysis system for resolving poorly separated peaks. The
      separation capacity is a special case of a broader metric of the separation
      measure which is a function of column efficiency, solute separability, and the
      level of the solute interaction with a column stationary phase. The formulae for
      theoretical prediction of all these metrics for arbitrary pairs of peaks in
      static analyses are derived. To provide a better insight into the basic metrics
      of the separation performance, additional metrics such as the solute
      discrimination (relative difference in solute velocities), utilization of
      separability (solute discrimination per unit of their separability), specific
      separation (the separation per unit of separability), and others are defined and
      found for static analyses.

PMID- 21742339
TI  - Synthesis and assembly of gold nanoparticle-doped polymer solid foam films at the
      liquid/liquid interface and their catalytic properties.
AB  - Gold nanoparticle-doped poly(2-vinylpyridine) (P2VP) microcapsules and foam films
      were synthesized and assembled at the P2VP chloroform solution/HAuCl(4) aqueous
      solution interface at 25  degrees C. It was found that Au nanoparticles with the
      average diameter of 2.1 nm were homogeneously embedded in and adsorbed on the
      walls of the capsules and foams, the nanoparticles were composed of Au(0) and
      Au(III) with the molar ratio of about 75/25, and the mass percent of Au elements
      was measured to be 19.65%. The formation of the nanostructures was attributed to
      the self-assembly of P2VP at the liquid/liquid interface, the simultaneous
      reduction of AuCl(4)(-) ions by a small amount of ethanol in the chloroform and
      adsorption of AuCl(4)(-) ions. After irradiated by UV-light for 1h, the average
      diameter of the nanoparticles was found to be 2.2 nm, and the AuCl(4)(-) ions
      were transformed to Au(0) completely. The catalytic performance of these
      composite nanostructures were evaluated by using the reduction of 4-nitrophenol
      (4-NP) by potassium borohydride in aqueous solutions. The catalytic activity was
      very high in the first cycle, decreased rapidly and slightly in the second and
      third cycles, respectively, due to the aggregation of some nanoparticles, and
      stabilized after the third cycle.

PMID- 21742340
TI  - Effect of Triton X-100 on the stability of aqueous dispersions of copper
      phthalocyanine pigment nanoparticles.
AB  - The effect of Triton X-100 on the colloidal dispersion stability of CuPc-U
      (unsulfonated and hydrophobic) and CuPc-S (surface sulfonated and hydrophilic)
      particles in aqueous solutions (water and NaNO(3)) was investigated at 25 
      degrees C. Its adsorption density was determined from surfactant concentrations
      analyzed by an HPLC method with a UV detector. The experimental dispersion
      stability ratios of the particles were determined from dynamic light scattering
      (DLS) data, with the Rayleigh-Debye-Gans (RDG) light scattering theory. The
      adsorption densities of Triton X-100 on both the CuPc-U and CuPc-S increase with
      increasing concentration of surfactant up to the critical micelle concentration
      (cmc), and then reach a plateau. The maximum adsorption density Gamma(m) is
      higher for the CuPc-U (d(h)=160 nm) than that for the CuPc-S (d(h)=90 nm). The
      hydrophobic chains are inferred to be adsorbed onto the surfaces, and the
      hydrophilic ethylene oxide chains are in a coil conformation. The W(app)-values
      for the CuPc-U dispersions are affected mainly by the surfactant fractional
      surface coverage theta. Adding NaNO(3) has no significant effect on the
      dispersion stability. The stabilization mechanism for the CuPc-U is inferred to
      be primarily steric, as expected. The stability ratios for the CuPc-S in
      solutions with NaNO(3) are higher than those for CuPc-U, and decrease with
      increasing concentration of NaNO(3), indicating that the stabilization is
      affected by the screening of electrostatic repulsive forces. The zeta potential
      is not a good predictor of the electrostatic stabilization, pointing to the need
      for new and improved theories.

PMID- 21742341
TI  - Chelating template-induced encapsulation of NiO cluster in mesoporous silica via
      anionic surfactant-templated route.
AB  - In this study, we develop a novel one-step method for synthesis of nickel
      oxide/silicon dioxide (NiO/SiO(2)) mesoporous composites by using N-hexadecyl
      ethylenediamine triacetate (HED3A) as structure-directing agent. Besides playing
      a role in directing the mesophase formation, the anionic surfactant also
      functions as a chelating agent that binds nickel ions. Ultraviolet-visible (UV
      vis) and Fourier transform infrared (FTIR) spectroscopic analyses were undertaken
      to determine the chelating ability between HED3A and nickel ions. By adjusting
      the molar ratio of Ni(2+)/HED3A in the template solution, a series of mesoporous
      composites with various NiO contents were obtained after calcination. These
      composites were characterized by X-ray diffraction (XRD), high resolution
      transmission electron microscopy (HRTEM), and nitrogen adsorption/desorption. The
      results showed that the generated NiO nanoparticles were aggregated into clusters
      with the size less than 20 nm, and the composites retained mesoporous
      characteristics even with high NiO contents. HRTEM images also revealed the
      migration and aggregation for NiO nanoparticles during the sintering process.
      Moreover, the energy-dispersive X-ray spectrum (EDX) results showed a close
      linear relationship between Ni/Si in the composites and Ni(2+)/HED3A in the
      templates. This chelating surfactant-assistant encapsulation route has the
      potential to synthesize diversiform metal oxide/silica mesoporous composites with
      designated compositions.

PMID- 21742342
TI  - On modeling incipient crystallization of sparingly soluble salts in frontal
      membrane filtration.
AB  - Modeling incipient crystallization ("scaling") in desalination membrane modules
      is a very difficult task due to several complications arising from the interplay
      of physico-chemical solution conditions (leading to supersaturation) with the
      flow field and related transport processes, including solid phase generation
      phenomena and membrane surface geometrical changes caused by the developing
      discrete particles. Although eventually all these aspects must be included in a
      comprehensive process model, it is fruitful to isolate and tackle them
      separately, thereby improving our understanding and developing techniques which
      will facilitate the ensuing synthesis of an integrated modeling framework. The
      focus in this work is on solid phase generation phenomena accounting for the
      membrane surface geometrical changes. A mean field model is developed that
      includes bulk and surface particle nucleation and growth processes. The relative
      importance of the two types of processes is analyzed. It is shown that, if thick
      concentration boundary layers exist around surface particles, the mean field
      theory--although not strictly valid--can be approximately used to estimate the
      transport coefficients, in conjunction with a unit cell problem for transport
      processes around a single surface particle. The unit cell problem is formulated
      and typical results for the flow and concentration field therein are presented as
      well as the corresponding mass transfer coefficients.

PMID- 21742343
TI  - Sorption behaviour of nanocrystalline MOR type zeolite for Th(IV) and Eu(III)
      removal from aqueous waste by batch treatment.
AB  - The nanocrystalline mordenite (MOR) type zeolite materials with initial chemical
      composition Na(2)O:Al(2)O(3):10SiO(2):48H(2)O have been synthesized under
      hydrothermal conditions. MOR1 and MOR2 are spherically shaped nanocrystals,
      whereas MOR3 and MOR4 have rod-like morphology. This paper reports the sorption
      characteristics of MOR analogues for Th(IV) and Eu(III) removal from aqueous
      nuclear waste. Sorption of Th(IV) and Eu(III) on MOR1, MOR2, MOR3 and MOR4 in a
      single component system with varying initial metal ion concentration, solution
      pH, contact times, sorbent dose and temperatures has also been investigated.
      Further, the Langmuir and Freundlich sorption models have been applied to
      describe equilibrium isotherms at different temperatures. The adsorption capacity
      increases largely with increasing solution pH and temperature of the system.
      Specific surface area and pore volume have been investigated by Brunauer-Emmett
      Teller (BET) method. The N(2) adsorption isotherm presents a type IV isotherm
      with narrow hysteresis loop which indicates the presence of mesopores related to
      inter-particle voids. Thermodynamic results indicate that the sorption follows an
      endothermic physisorption process. It has been found that these exchangers have
      good sorption capacity and out of which MOR4 has highest sorption capacity. Thus,
      nanocrystalline MOR4 is proved to be good sorbent for both Th(IV) and Eu(III).

PMID- 21742344
TI  - Periodic mesoporous organosilicas with bis(8-quinolinolato) dioxomolybdenum(VI)
      inside the channel walls.
AB  - Novel periodic mesostructured organometallic silicas of MCM-41 type bearing
      homogeneously distributed bis(8-quinolinolato)dioxomolybdenum(VI) inside the
      channel walls (denoted as MoO(2)Q(2)@PMO-x) are synthesized via a convenient one
      pot method and examined as catalysts in the epoxidation of cyclooctene. The
      ordered mesoporous structures as well as the organometallic groups incorporated
      into the framework are fully determined by comprehensive characterization
      techniques such as XRD, TEM, N(2) adsorption/desorption, SEM, FT-IR, UV-vis
      spectroscopy, solid-state NMR, ICP-AES, XPS and TG/DSC. MoO(2)Q(2)@PMO-6%
      catalyst exhibits higher activity for the epoxidation of cyclooctene with tert
      butyl hydroperoxide than other MoO(2)Q(2)@PMO materials and its homogeneous or
      randomly grafted analogue.

PMID- 21742345
TI  - Substance use disorders and comorbid Axis I and II psychiatric disorders among
      young psychiatric patients: findings from a large electronic health records
      database.
AB  - This study examined the prevalence of substance use disorders (SUDs) among
      psychiatric patients aged 2-17 years in an electronic health records database
      (N=11,457) and determined patterns of comorbid diagnoses among patients with a
      SUD to inform emerging comparative effectiveness research (CER) efforts. DSM-IV
      diagnoses of all inpatients and outpatients at a large university-based hospital
      and its associated psychiatric clinics were systematically captured between 2000
      and 2010: SUD, anxiety (AD), mood (MD), conduct (CD), attention
      deficit/hyperactivity (ADHD), personality (PD), adjustment, eating, impulse
      control, psychotic, learning, mental retardation, and relational disorders. The
      prevalence of SUD in the 2-12-year age group (n=6210) was 1.6% and increased to
      25% in the 13-17-year age group (n=5247). Cannabis diagnosis was the most
      prevalent SUD, accounting for more than 80% of all SUD cases. Among patients with
      a SUD (n=1423), children aged 2-12 years (95%) and females (75-100%) showed high
      rates of comorbidities; blacks were more likely than whites to be diagnosed with
      CD, impulse-control, and psychotic diagnoses, while whites had elevated odds of
      having AD, ADHD, MD, PD, relational, and eating diagnoses. Patients with a SUD
      used more inpatient treatment than patients without a SUD (43% vs. 21%);
      children, females, and blacks had elevated odds of inpatient psychiatric
      treatment. Collectively, results add clinical evidence on treatment needs and
      diagnostic patterns for understudied diagnoses.

PMID- 21742346
TI  - Neurogenic muscle hypertrophy in type III spinal muscular atrophy.
AB  - Neurogenic muscle hypertrophy is very unusual and has been rarely described. We
      described a 25-year-old woman presented with proximal muscle weakness with calf
      muscle hypertrophy. Limb magnetic resonance imaging scans showed increased muscle
      bulk without fatty changes, and a muscle biopsy revealed prominent hypertrophic
      type II muscle fibers. A mutation in SMN1 was found in a genetic analysis. This
      is the first report of neurogenic muscle hypertrophy seen in genetically
      confirmed spinal muscular atrophy III.

PMID- 21742348
TI  - Emergency surgery for macrocystic lymphatic malformation in the lung of a
      neonate.

PMID- 21742347
TI  - Eight hours of cold static storage with adenosine and lidocaine (Adenocaine)
      heart preservation solutions: toward therapeutic suspended animation.
AB  - OBJECTIVE: Most cardiac preservation solutions provide safe cold ischemic storage
      times for 4 to 5 hours. Our aim was to investigate the effects of 8 hours of cold
      static storage (4 degrees C) using 2 normokalemic, polarizing adenosine-lidocaine
      (Adenocaine; Hibernation Therapeutics Global Ltd, Kilquade, Ireland) solutions
      and to compare their functional recovery with hearts preserved in gold standard
      histidine-tryptophan-ketoglutarate (Custodiol-HTK; Essential Pharma, Newtown, Pa)
      and Celsior (Genzyme, Cambridge, Mass) solutions. METHODS: Male Sprague-Dawley
      rats (350-450 g) were randomly assigned to 1 of 4 groups (n = 8): (1) adenosine
      lidocaine cardioplegia with low Ca(2+)/high Mg(2+); (2) 2* adenosine-lidocaine
      cardioplegia, low Ca(2+)/high Mg(2+), melatonin, and insulin (2* adenosine,
      lidocaine, melatonin, and insulin); (3) histidine-tryptophan-ketoglutarate
      solution; or (4) Celsior. Hearts were perfused in working mode, arrested (37
      degrees C), removed, stored for 8 hours at 4 degrees C, reattached in Langendorff
      mode and rewarmed for 5 minutes (37 degrees C), and switched to working mode for
      60 minutes. Myocardial oxygen consumption, effluent lactates, and troponin T
      levels were measured. RESULTS: Hearts preserved for 8 hours in adenosine
      lidocaine and 2* adenosine, lidocaine, melatonin, and insulin returned 50% and
      76% of aortic flow and 70% and 86% of coronary flow, respectively, at 60 minutes
      of reperfusion. In contrast, Custodiol-HTK and Celsior hearts returned 2% and 17%
      of aortic flow and 11% and 48% of coronary flow, respectively, at 60 minutes of
      reperfusion. Hearts preserved in adenosine-lidocaine and 2* adenosine, lidocaine,
      melatonin, and insulin returned 90% and 100% of developed pressures and 101% and
      104% of heart rate, respectively. Hearts preserved in histidine-tryptophan
      ketoglutarate failed to increase systolic pressure greater than 14 mm Hg (11%
      baseline) and diastolic pressure greater than 10 mm Hg (17% baseline), and
      recovered only 16% of heart rate. Hearts preserved in Celsior developed 70% of
      baseline systolic pressures and 86% recovery of heart rate. At 5 minutes of
      rewarming after cold storage, the myocardial oxygen consumption for hearts
      preserved in adenosine-lidocaine, 2* adenosine, lidocaine, melatonin, and
      insulin, Custodiol-HTK, and Celsior was 23.0 +/- 5, 20 +/- 4, 15 +/- 1, and 10 +/
      2 MUmol O(2)/min/g dry wt, respectively, with corresponding lactate outputs of
      1.8 +/- 0.8, 1.5 +/- 0.7, 2.6 +/- 0.7, and 3.2 +/- 1.4 MUmol lactate/min/g dry
      weight. Troponin T was not detected in the coronary effluent of adenosine
      lidocaine or 2* adenosine, lidocaine, melatonin, and insulin hearts, whereas
      Custodiol-HTK and Celsior hearts had troponin T levels of 0.08 and 0.24 MUg/mL,
      respectively. CONCLUSIONS: We report a 78% return of cardiac output, 90% to 100%
      return of developed pressures, and 101% to 104% return of heart rate after 8
      hours of cold static storage using normokalemic, adenosine, lidocaine, melatonin,
      and insulin preservation solution in the isolated rat heart compared with 55%
      cardiac output with polarizing adenosine-lidocaine cardioplegia alone, 4% cardiac
      output with Custodiol-HTK, and 25% cardiac output in Celsior preservation
      solutions.

PMID- 21742349
TI  - A randomized evaluation of simulation training on performance of vascular
      anastomosis on a high-fidelity in vivo model: the role of deliberate practice.
AB  - OBJECTIVES: There is mounting evidence supporting the benefit of surgical skills
      practice in a simulated environment. However, the use of simulation in cardiac
      surgical training has been limited. The purpose of the current trial was to
      examine the effect of independent and deliberate simulator practice, during
      nonclinical time, on the performance of an end-to-side microvascular anastomosis
      in an in vivo model. METHODS: This single-blinded, randomized controlled trial
      received institutional review board approval. Thirty-nine first- and second-year
      surgical trainees were randomized to an expert-guided tutorial on a procedural
      trainer or to the expert-guided tutorial combined with self-directed practice on
      the same procedural trainer. Self-directed practice consisted of 10 anastomoses
      performed on the procedural trainer: a low-fidelity, commercially available bench
      model using 4-mm polytetrafluoroethylene graft as simulated blood vessel. Two
      weeks after the tutorial, subjects performed an end-to-side anastomosis in a live
      porcine model, under realistic operating room conditions. Assessment of outcomes
      was performed by 2 blinded, expert observers, uings validated measurements of
      technical skill. The primary outcome was the score on the Objective Structured
      Assessment of Technical Skill (OSATS) scale. Secondary outcomes included an
      anastomosis-specific end-product evaluation and time to completion. Statistical
      analysis was conducted using nonparametric, univariate techniques. RESULTS:
      Compared with residents who received expert-guided simulator training alone,
      those who in addition practiced on a simulator independently after hours scored
      significantly higher on the OSATS scale (23.7 +/- 4.7 vs 18.5 +/- 3.9, P = .003).
      Residents who practiced independently also scored significantly higher on the end
      product evaluation (11.4 +/- 3.2 vs 8.9 +/- 2.1, P = .02) and performed the
      anastomosis significantly faster (777 seconds vs 977 seconds, P = .04).
      Interrater reliability was high between the expert observers (intraclass
      correlation coefficient = 0.8). CONCLUSIONS: Residents who had the opportunity
      for self-directed simulator practice performed an end-to-side anastomosis more
      adeptly, more quickly, and with a higher quality end product. The results of this
      randomized trial suggest that independent training on a procedural trainer did
      transfer to improved performance in an operating room environment. Simulator
      training should be incorporated into cardiovascular surgical curricula and
      residents should have access to this modality for independent after-hours
      practice to improve operating room performance.

PMID- 21742351
TI  - Microplastics in the marine environment.
AB  - This review discusses the mechanisms of generation and potential impacts of
      microplastics in the ocean environment. Weathering degradation of plastics on the
      beaches results in their surface embrittlement and microcracking, yielding
      microparticles that are carried into water by wind or wave action. Unlike
      inorganic fines present in sea water, microplastics concentrate persistent
      organic pollutants (POPs) by partition. The relevant distribution coefficients
      for common POPs are several orders of magnitude in favour of the plastic medium.
      Consequently, the microparticles laden with high levels of POPs can be ingested
      by marine biota. Bioavailability and the efficiency of transfer of the ingested
      POPs across trophic levels are not known and the potential damage posed by these
      to the marine ecosystem has yet to be quantified and modelled. Given the
      increasing levels of plastic pollution of the oceans it is important to better
      understand the impact of microplastics in the ocean food web.

PMID- 21742352
TI  - Drug-drug interactions in HIV medicine: a not so simple and straightforward road
      to the future.

PMID- 21742353
TI  - Leptin and the skeleton-where is the fat?

PMID- 21742354
TI  - Rings D-seco and B,D-seco tetranortriterpenoids from root bark of Entandrophragma
      angolense.
AB  - Investigation of the root bark extract of Entandrophragma angolense led to
      identification of two gedunin-type limonoids 5-hydroxy-7-deacetoxy-7-oxogedunin
      and 5,6-dehydro-7-deacetoxy-7-oxogedunin, and three methyl angolensate
      derivatives, 6-deacetoxydomesticulide D, 6-deacetoxydomesticulide D 21
      methylether, and entangosin, together with known compounds, methyl angolensate, 6
      acetoxymethyl angolensate and secomahoganin. Their structures were established by
      extensive NMR experiments in conjunction with mass spectrometry. Entangosin is a
      rare example of a limonoid derivative having a fully O-substituted furan moiety.

PMID- 21742355
TI  - [Primary mesenteric extraskeletal osteosarcoma: imaging findings].
AB  - We present a case of extraskeletal osteosarcoma arising from the root of the
      mesentery. This location is extremely rare; to our knowledge only three other
      cases have been reported. We describe the findings at computed tomography,
      positron emission tomography, and bone scintigraphy. We emphasize the radiologic
      differential diagnosis in this case, which was complicated by the presence of
      other malignant abdominal disease.

PMID- 21742356
TI  - [Fractures and infectious processes in the face].
AB  - Facial trauma occurs relatively often in traffic accidents, work accidents, and
      aggression, causing repercussions in the functionality of the structures
      involved. Infectious processes require early and accurate diagnosis because they
      can progress quickly, leading to unexpected complications, or because of the
      severity of the infections themselves.

PMID- 21742357
TI  - [Multidetector computed tomography in acute abdomen].
AB  - MDCT has become a fundamental tool for determining the causes of acute abdomen.
      CT is considered the imaging technique of choice in the diagnostic workup of both
      localized and diffuse acute abdomen, except in patients in whom acute
      cholecystitis or acute gynecological disease is suspected and in children,
      adolescents, and pregnant patients, in whom ultrasonography is the imaging
      technique of choice. Plain-film X-ray examination has been relegated to the
      initial management of renal colic, suspected foreign bodies, and intestinal
      obstruction. One of the drawbacks of MDCT is its use of ionizing radiation, which
      makes it necessary to filter and direct the examinations as well as to ensure
      that the most appropriate protocols are used. For this reason, low dose protocols
      have been developed so that diagnostic studies can be performed with doses of
      radiation between 2 and 3 mSv; these are normally used in the diagnosis of renal
      colic and can also be used in selected patients with suspected appendicitis and
      acute diverticulitis.

PMID- 21742358
TI  - [Ameloblastoma of the jaws. A retrospective analysis from 1994 to 2007].
AB  - INTRODUCTION: Ameloblastomas and keratocysts are the most frequent epithelial
      odontogenic tumors of the jaws. They have a high recurrence rate. This
      retrospective study reviews the features of ameloblastomas operated on in our
      unit from 1994 to 2007. PATIENTS AND METHODS: The studied parameters were sex,
      ethnic origin, age at diagnosis, clinical signs, radiographic presentation, site
      distribution, histological type, treatment, and follow-up records. RESULTS: One
      hundred and sixteen patients were included (with 239 surgical samples). The mean
      age was 36 years, with a majority of Europeans, 60% of multilocular radiolucent
      lesions with root resorption, mandibular location (93%). Twenty-one percent of
      the patients presented with an impacted tooth, the third molar in 79% of cases.
      Fifty percent of the lesions were from 5 to 13cm in length, 10% longer than 13cm.
      The most common histological type was follicular ameloblastoma. Patients were
      treated by enucleation in 82% of cases and radical mandibular resection with
      reconstruction in 11% of cases. The follow-up was documented for 96% of the
      patients with a 44% recurrence rate. Seventy-four percent of patients with a
      double recurrence presented with a "follicular" ameloblastoma. DISCUSSION: We
      prefer a well-performed enucleation which preserves surrounding bone. The high
      rate of follicular type recurrence should more systematically lead to a combined
      treatment: periostectomy and tooth extraction. Our data was compared with
      previously published large series.

PMID- 21742359
TI  - [Ethnosurgery or reflecting on how others perceive you when on humanitary
      mission].

PMID- 21742360
TI  - Comparison between spontaneous sedimentation method and Paratest(r) for the
      diagnosis of intestinal parasitic infections.
AB  - Correct diagnosis of parasitic infections is essential for the treatment of
      individuals avoiding indiscriminate use of anthelmintics which increases drug
      resistance. In a comparative study between the spontaneous sedimentation
      technique and Paratest((r)), 140 stool samples were analyzed for the detection of
      parasites. The prevalence was 12.7% obtained by the spontaneous sedimentation
      method but only 5.7% using Paratest((r)). Paratest((r)) has shown a high
      proportion of false-negative results, lower sensitivity and negative predictive
      values compared with the spontaneous sedimentation method. Further optimization
      and studies of the Paratest((r)) method are necessary for wider use in clinical
      diagnosis.

PMID- 21742361
TI  - Iron deficiency anaemia and blood lead concentrations in Brazilian children.
AB  - This study investigated the relationship between iron deficiency/iron deficiency
      anaemia, assessed by several parameters, and blood lead concentration in
      children. This cross-sectional study involved 384 Brazilian children, aged 2-11
      years, who lived near a lead-manipulating industry. Complete blood counts were
      obtained by an automated cell counter. Serum iron, total iron binding capacity
      (TIBC) and ferritin were determined respectively, by colorimetric, turbidimetric
      methods and chemiluminescence. Blood lead was measured by atomic absorption
      spectrophotometry. The impact of several parameters for assessment of iron status
      (haemoglobin, serum iron, TIBC, transferrin saturation, ferritin, red cell
      indices and red cell distribution width) and variables (gender, age, mother's
      education, income, body mass index, iron intake, and distance from home to lead
      manipulating industry) on blood lead concentration was determined by multiple
      linear regression. There were significant negative associations between blood
      lead and the distance from home to the lead-manipulating industry (P<0.001), Hb
      (P=0.019), and ferritin (P=0.023) (R(2)=0.14). Based on these results, further
      epidemiological studies are necessary to investigate the impact of interventions
      like iron supplementation or fortification, as an attempt to decrease blood lead
      in children.

PMID- 21742362
TI  - Outcomes of 19 pregnant women with brucellosis in Babol, northern Iran.
AB  - From April 2000 to March 2010, 19 pregnant women with brucellosis were evaluated,
      treated and followed up. Ten (53%) pregnant women had spontaneous abortions. Six
      of eleven (55%) women infected in the first trimester had a spontaneous abortion.
      After treatment, all subsequently became pregnant and gave birth to normal
      babies. Among 13 patients who received cotrimoxazole plus rifampin, only four
      (31%) aborted and nine mothers had normal term deliveries. Two patients with
      recurrent abortions had brucellosis and became pregnant and gave birth after
      treatment. The brucellosis screening program for pregnant women and those with
      spontaneous abortion is necessary in brucellosis endemic regions.

PMID- 21742363
TI  - Involvement of Noxa in mediating cellular ER stress responses to lytic virus
      infection.
AB  - Noxa is a Bcl-2 homology domain-containing pro-apoptotic mitochondrial protein.
      Noxa mRNA and protein expression are upregulated by dsRNA or virus, and ectopic
      Noxa expression enhances cellular sensitivity to virus or dsRNA-induced
      apoptosis. Here we demonstrate that Noxa null baby mouse kidney (BMK) cells are
      deficient in normal cytopathic response to lytic viruses, and that reconstitution
      of the knockout cells with wild-type Noxa restored normal cytopathic responses.
      Noxa regulation by virus mirrored its regulation by proteasome inhibitors or ER
      stress inducers and the ER stress response inhibitor salubrinal protected cells
      against viral cytopathic effects. Noxa mRNA and protein were synergistically
      upregulated by IFN or dsRNA when combined with ER stress inducers, leading to
      Noxa/Mcl-1 interaction, activation of Bax and pro-apoptotic caspases, degradation
      of Mcl-1, loss of mitochondrial membrane potential and initiation of apoptosis.
      These data highlight the importance of ER stress in augmenting the expression of
      Noxa following viral infection.

PMID- 21742364
TI  - Osteopontin upregulation in rotavirus-induced murine biliary atresia requires
      replicating virus but is not necessary for development of biliary atresia.
AB  - Biliary atresia (BA) is a progressive fibro-inflammatory pediatric liver disease
      in which osteopontin (OPN), a glycoprotein with inflammatory and fibrogenic
      activity, may play a pathogenic role. The current studies were conducted in a
      mouse model of rotavirus-induced BA to test the hypotheses that live but not
      inactivated rotavirus causes antigenemia, upregulation of hepatic OPN expression,
      and induction of BA and fibrosis; and that OPN is necessary for development of
      BA. Prolonged or transient antigenemia developed in mice inoculated with live or
      inactivated virus, respectively, but only live virus upregulated hepatic OPN and
      caused BA and fibrosis. OPN was expressed in intra- and extrahepatic bile ducts
      in healthy mice and in mice with BA. OPN-deficient mice, similar to WT mice,
      developed BA. Together, these data show that live but not inactivated rotavirus
      causes upregulation of hepatic OPN expression and BA but that OPN is not
      necessary for development of BA.

PMID- 21742365
TI  - Ionic liquids for extraction of metals and metal containing compounds from
      communal and industrial waste water.
AB  - In a fundamental study the potential of ionic liquids based on quaternary
      ammonium- and phosphonium cations and thiol-, thioether-, hydroxyl-, carboxylate-
      and thiocyanate-functionalized anions has been assessed for future application in
      advanced sewage treatment. The elimination of the metal(oid)s Ag, As, Cd, Cr, Cu,
      Hg, Ni, Pb, Pt, Sn, Zn and the cancerostatic platinum compounds cisplatin and
      carboplatin was screened using a liquid phase micro-extraction set-up. The
      analytical tool-set consisted of ICP-SFMS and LC-ICP-MS for quantification of
      metal(oid)s and cancerostatic platinum compounds, respectively. The purity of the
      ILs was assessed for the investigated metal(oid)s on the base of present EU
      environmental quality standards and was found to be sufficient for the intended
      use. In model solutions at environmental relevant concentrations extraction
      efficiencies>=95% could be obtained for Ag, Cu, Hg and Pt with both phosphonium-
      and ammonium-based ILs bearing sulphur functionality in the form of
      thiosalicylate and 2-(methylthiobenzoate) anions, as well as with
      tricaprylmethylammonium thiocyanate within an extraction time of 120 min. All
      other metals were extracted to a lower extent (7-79%). In the case of
      cancerostatic platinum compounds a phosphonium-based IL bearing thiosalicylate
      functionality showed high extraction efficiency for monoaquacisplatin. For the
      first time, liquid phase micro extraction with ionic liquids was applied to
      industrial and communal waste water samples. The concentration of all
      investigated metal(oid)s could be significantly reduced. The degree of
      elimination varied with the initial concentration of metals, pH and the amount of
      suspended particulate matter.

PMID- 21742366
TI  - Partitioning of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS) and
      perfluorooctane sulfonamide (PFOSA) between water and sediment.
AB  - Laboratory partitioning experiments were conducted to elucidate the sorption
      behaviour and partitioning of perfluoroalkyl compounds (PFCs). Three different
      sediment types were used and separately spiked with perfluorooctanoate (PFOA),
      perfluorooctane sulfonate (PFOS) and perfluorooctane sulfonamide (PFOSA) at low
      environmentally realistic concentrations. PFOA, PFOS and PFOSA were mainly
      distributed in the dissolved phase at low suspended solid concentrations,
      indicating their long-range transport potential in the marine environment. In all
      cases, the equilibrium isotherms were linear and the organic carbon normalised
      partition coefficients (K(OC)) decreased in the following order: PFOSA (log K(OC)
      = 4.1 +/- 0.35 cm3 g-1)>PFOS (3.7 +/- 0.56 cm3 g-1) > PFOA (2.4 +/- 0.12 cm3 g
      1). The level of organic content had a significant influence on the partitioning.
      For the sediment with negligible organic content the density of the sediment
      became the most important factor influencing the partitioning. Ultimately, data
      on the partitioning of PFCs between aqueous media and suspended solids are
      essential for modelling their transport and environmental fate.

PMID- 21742367
TI  - Pine needles as passive bio-samplers to determine polybrominated diphenyl ethers.
AB  - Eight polybrominated diphenyl ethers (PBDEs) were determined in pine needles of
      three species (Pinus halepensis, Pinus pinea and Pinus nigra) collected in the NE
      Spain in an attempt to use this matrix for the biomonitoring of airborne PBDEs.
      The method used was based in ultrasonic extraction followed by alumina and
      Florisil clean-up and determination by gas chromatography coupled to mass
      spectrometry in negative chemical ionization. Recoveries were between 99% and
      138%, limits of detection between 0.011 and 0.070 ng g(-1)-dw (0.232 ng g(-1)-dw
      for BDE 209) and repeatability lower than 13%. PBDE levels ranged between 0.027
      ng g(-1)-dw and 13.04 ng g(-1)-dw, with predominance of BDE 209, followed by BDEs
      47. P. halepensis was the species with the highest PBDE levels and P. nigra, the
      least, according to their widespread and remote distribution, respectively. The
      presence of PBDEs in pine needles was attributed to the release of in-use PBDEs,
      transport through atmosphere and adsorption upon lipid rich pine needles. Given
      the easy collection of pine needles, its ample distribution and its potential to
      accumulate airborne contaminants, this matrix is proposed as passive bio-sampler
      to be used in PBDE monitoring programs. CAPSULE: Pine needles can be used to
      biomonitor airborne PBDEs.

PMID- 21742368
TI  - Immunocytochemical and immunohistochemical methods as auxiliary techniques for
      histopathological diagnosis of cutaneous leishmaniasis.
AB  - A significant increase in cutaneous leishmaniasis (CL) and its geographic
      expansion has motivated the development of techniques to help with diagnosis of
      the disease. Here we describe immunocytochemical (ICC) and immunohistochemical
      (IHC) techniques for the diagnosis of CL in the laboratory. Polyclonal antibodies
      and a modified avidin-biotin complex (Ultra Streptavidin((r))) for Leishmania
      (V.) braziliensis or Leishmania (L.) amazonensis were developed for the present
      study. In vitro culture and histological sections from experimentally infected
      tissues were submitted to ICC/IHC techniques. The polyclonal antibody
      specificity, stability and immunostaining were evaluated. The polyclonal
      antibodies purified by chromatography (Sephadex((r))) and obtained from L. (V.)
      braziliensis and L. (L.) amazonensis insoluble antigens presented 83.3%
      sensitivity, when the presence of antigens was evaluated, i.e., higher than
      histopathology or any equivalent method (in vitro culture). The polyclonal
      antibody presented 100% specificity when used against species frequently found in
      CL lesions. The ICC/IHC techniques developed in the current study were able to
      recognize amastigotes and antigens from in vivo and in vitro cultures and from
      biopsies, offering additional help in the diagnosis of CL. This methodology could
      be beneficially adopted in public health laboratories.

PMID- 21742369
TI  - Retrospective review of an intraoperative algorithm to predict lymph node
      metastasis in low-grade endometrial adenocarcinoma.
AB  - OBJECTIVE: To validate the Mayo algorithm to intraoperatively identify women with
      endometrial cancer in whom lymphadenectomy may be safely omitted. METHODS: A
      multi-center retrospective chart review 1977-2010 was completed using two
      independent institutional endometrial cancer databases. Eligibility criteria were
      grade 1 or 2 endometrial carcinoma, low-risk histology, and myometrial invasion
      <= 50% on intraoperative pathology consultation; patients were considered to
      satisfy the Mayo criteria if, in addition to these, tumor diameter on the final
      pathology report was <= 2 cm. Analysis of nodal metastases, recurrent disease,
      and progression-free survival (PFS) using the Kaplan-Meier method was performed.
      RESULTS: Six hundred and two patients met inclusion criteria for the study. Of
      110 patients satisfying the Mayo algorithm with an adequate lymphadenectomy, 2
      (1.8%) were diagnosed with lymph node metastasis and 4 (3.6%) subsequently
      developed recurrent disease. The Mayo algorithm identified with a 98.2% negative
      predictive value women who would not benefit from a lymphadenectomy. There was no
      significant difference in recurrence rate or PFS between women who underwent
      lymphadenectomy and those who did not when the Mayo algorithm was satisfied.
      CONCLUSIONS: The Mayo algorithm intraoperatively identifies tumor characteristics
      of low-risk disease in endometrial carcinoma that predict a very low likelihood
      of nodal metastasis and recurrence. Although a small number of patients with
      advanced stage disease may be missed when applying the Mayo criteria, there is no
      apparent survival benefit to lymphadenectomy for patients satisfying this
      algorithm, and these data support its use at other institutions.

PMID- 21742370
TI  - The association between endometriosis and gynecological cancers and breast
      cancer: a review of epidemiological data.
AB  - OBJECTIVE: This article critically reviews the literature on the association
      between endometriosis and gynecological cancers and breast cancer, based on
      epidemiologic data. METHODS: Literature review of the English language literature
      based on searching in the MEDLINE (PubMed) database and additional collection of
      reports by systematically reviewing all references from retrieved papers.
      RESULTS: Data from large cohort and case-control studies indicate that
      endometriosis patients only have an increased risk of ovarian cancer among the
      gynecological malignancies and breast cancer, although most of the observed
      associations are modest. Data on the association between endometriosis and breast
      cancer are inconsistent. Endometriosis patients have a reduced risk of cervical
      cancer, and there is no association between endometriosis and endometrial cancer.
      Endometriosis-associated ovarian cancer seems to be a distinct clinical entity;
      patients are younger, diagnosed in earlier stages, have lower grade lesions and a
      better survival. Further, endometriosis-associated ovarian cancers are
      predominantly clear cell and endometrioid histologic subtypes. CONCLUSIONS:
      Endometriosis seems to be a precursor of epithelial ovarian cancer, especially
      clear cell and endometrioid adenocarcinomas. However, current evidence is
      insufficient to draw any definitive conclusions whether this association
      represents causality or the sharing of similar risk factors and/or antecedent
      mechanisms.

PMID- 21742371
TI  - Clinicopathologic significance of DNA mismatch repair protein defects and
      endometrial cancer in women 40years of age and younger.
AB  - BACKGROUND: The hereditary basis of endometrial cancer is apparent in young women
      with endometrial cancer. The objective of this study was to examine risk factors
      and outcomes in patients 40 years of age and younger with endometrial cancer.
      METHODS: We performed a retrospective cohort study of patients aged 40 years or
      less who were diagnosed with endometrial carcinoma between 1/93 and 5/08.
      Clinical and pathologic data were extracted from medical records. Paraffin
      embedded slides from hysterectomy specimens were obtained and DNA mismatch repair
      (MMR) immunohistochemistry was performed. Cases were analyzed according to the
      presence of DNA MMR protein defects. Standard two-sided statistical tests were
      performed. RESULTS: Of the 56 identified patients, the median age was 36 years
      (range, 24-40). The majority of the endometrial carcinomas were of endometrioid
      histology (91%), stage I (71%), and FIGO grade 1 (59%). Abnormal DNA MMR was
      found in 9 cases (16%). Cases with abnormal DNA MMR had lower body mass index
      (BMI) (P=0.05), and had a family history suggestive of Lynch syndrome (P=0.001).
      Tumors were more likely to have advanced stage disease (P<0.001), be high grade
      (P<0.001), have deep myometrial invasion (P<0.001), and have lymphovascular
      invasion (P=0.002). Cases with abnormal DNA MMR had significantly worse overall
      survival (P=0.028) and progression-free survival (P=0.042). CONCLUSIONS:
      Endometrial cancer is rare in women aged 40 years or less. In this group of
      patients, loss of DNA MMR was associated with lower BMI, worse clinicopathologic
      factors, and worse outcome. These results may have implications when young women
      diagnosed with endometrial cancer are counseled regarding prognosis.

PMID- 21742372
TI  - Incidence of mechanical malfunction in low-profile subcutaneous implantable
      venous access devices in patients receiving chemotherapy for gynecologic
      malignancies.
AB  - OBJECTIVE: The purpose of this study was to investigate the incidence of
      mechanical complications associated with low-profile subcutaneous implantable
      venous access devices in gynecologic oncology patients. METHODS: Gynecologic
      oncology patients with low-profile Port-a-Caths implanted between March 2005 and
      July 2006 were identified into a computerized database. Patient demographics,
      operative complications, number of chemotherapy cycles, duration of implantation,
      and mechanical complications were collected. Primary outcomes included port
      leakage, catheter fracture, and catheter embolization. RESULTS: 112 patients
      underwent 115 Port-a-Cath placements with low profile single-lumen plastic ports
      with Groshong-valved catheters. Mean Port-a-Cath indwelling duration was 197 days
      (range: 4-395) with a mean number of 12 chemotherapy cycles (range 0-64). The
      cumulative complication rate necessitating removal or replacement was 15%. Of the
      14 Port-a-Caths removed, ten (8.7%) were secondary to mechanical malfunction: one
      for leakage at the port site, two for catheter fracture, and seven for fracture
      with catheter embolization to the heart or pulmonary vasculature-most commonly
      the right ventricle. Patients with embolization were asymptomatic and all
      embolized catheters were successfully retrieved by interventional radiology
      without complications. CONCLUSIONS: The rates of catheter fracture and
      embolization have previously been reported to be low in patients with
      subcutaneous Port-a-Caths, and have not been studied in patients receiving low
      profile subcutaneous Port-a-Caths. This study suggests that catheter fracture may
      be more common (8.7%) and must be considered in patients with malfunctioning low
      profile Port-a-Caths. Embolized catheters can be removed by interventional
      radiology without significant adverse affects.

PMID- 21742373
TI  - Bilateral pheochromocytomas: incidental finding in a trauma patient.

PMID- 21742374
TI  - Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed
      atherosclerotic plaques.
AB  - In a number of literature reports iron oxide nanoparticles have been investigated
      for use in imaging atherosclerotic plaques and found to accumulate in plaques via
      uptake by macrophages, which are critical in the process of atheroma initiation,
      propagation, and rupture. However, the uptake of these agents is non-specific;
      thus the labeling efficiency for plaques in vivo is not ideal. We have developed
      targeted agents to improve the efficiency for labeling macrophage-laden plaques.
      These probes are based on iron oxide nanoparticles coated with dextran sulfate, a
      ligand of macrophage scavenger receptor type A (SR-A). We have sulfated dextran
      coated iron oxide nanoparticles (DIO) with sulfur trioxide, thereby targeting our
      nanoparticle imaging agents to SR-A. The sulfated DIO (SDIO) remained mono
      dispersed and had an average hydrodynamic diameter of 62 nm, an r(1) relaxivity
      of 18.1 mM(-1) s(-1), and an r(2) relaxivity of 95.8 mM(-1) s(-1) (37  degrees C,
      1.4 T). Cell studies confirmed that these nanoparticles were nontoxic and
      specifically targeted to macrophages. In vivo MRI after intravenous injection of
      the contrast agent into an atherosclerotic mouse injury model showed substantial
      signal loss on the injured carotid at 4 and 24 h post-injection of SDIO. No
      discernable signal decrease was seen at the control carotid and only mild signal
      loss was observed for the injured carotid post-injection of non-sulfated DIO,
      indicating preferential uptake of the SDIO particles at the site of
      atherosclerotic plaque. These results indicate that SDIO can facilitate MRI
      detection and diagnosis of vulnerable plaques in atherosclerosis.

PMID- 21742375
TI  - Enhanced bone-integration capability of alkali- and heat-treated nanopolymorphic
      titanium in micro-to-nanoscale hierarchy.
AB  - This study introduces nanopolymorphic features of alkali- and heat-treated
      titanium surfaces, comprising of tuft-like, plate-like, and nodular structures
      that are smaller than 100 nm and determines whether and how the addition of these
      nanofeatures to a microroughened titanium surface affects bone-implant
      integration. A comprehensive assessment of biomechanical, interfacial, and
      histological analyses in a rat model was performed for machined surfaces without
      microroughness, sandblasted-microroughened surfaces, and micro-nano hybrid
      surfaces created by sandblasting and alkali and heat treatment. The
      microroughened surface accelerated the establishment of implant biomechanical
      fixation at the early healing stage compared with the non-microroughened surface
      but did not increase the implant fixation at the late healing stage. The addition
      of the nanopolymorphic features to the microroughened surface further increased
      implant fixation throughout the healing time. The area of the new bone within 50
      MUm proximity of the implant surfaces, which was increased 2-3-fold using
      microroughened surfaces, was further increased 2-fold using nanopolymorphic
      surfaces. In contrast, the bone area in a 50-200 MUm zone was not influenced by
      either microroughened or nanopolymorphic surfaces. The percentage of bone-implant
      contact, which was increased 4-5-fold, using microroughened surfaces, was further
      increased substantially by over 2-fold throughout the healing period. The
      percentage of soft tissue intervention between bone and implant surfaces, which
      was reduced to half by microroughened surfaces, was additionally reduced by the
      nanopolymorphic surfaces to between one-third and one-fourth, resulting in only 5
      7% soft tissue intervention compared with 60-75% for the non-microroughened
      surface. Thus, using an exemplary alkali- and heat-treated nanopolymorphic
      surface, this study identified critical parameters necessary to describe the
      process and consequences of bone-implant integration, for which nanofeatures have
      specific and substantial roles beyond those of microfeatures. Nanofeature
      enhanced osteoconductivity, which resulted in both the acceleration and elevation
      of bone-implant integration, has clearly been demonstrated.

PMID- 21742376
TI  - Core-shell NaYF4:Yb3+,Tm3+@FexOy nanocrystals for dual-modality T2-enhanced
      magnetic resonance and NIR-to-NIR upconversion luminescent imaging of small
      animal lymphatic node.
AB  - New core-shell structured NaYF(4):Yb(3+),Tm(3+)@Fe(x)O(y) nanocrystals, with 20
      nm Yb(3+),Tm(3+)-co-doped NaYF(4) nanocrystals as a core and 5 nm Fe(x)O(y)
      nanocrystals as a shell, have been synthesized and characterized by TEM and XRD
      analysis. These core-shell nanocrystals exhibit excellent near-infrared
      upconversion luminescence (UCL) emission at 800 nm under excitation by a
      continuous-wave 980 nm laser and superparamagnetic properties with a saturation
      magnetization (Ms) of ~12 emu/g. Water-soluble nanocrystals were obtained by
      surface ligand exchange of oleic acid-coated precursor nanocrystals, and their
      internalization within living cells has been investigated by laser scanning UCL
      microscopy. Furthermore, the obtained core-shell nanocrystals have been applied
      in dual-modality T(2)-enhanced magnetic resonance (MR) and UCL imaging in vivo of
      the lymphatic system. Moreover, the toxicity of NaYF(4):Yb(3+),Tm(3+)@Fe(x)O(y)
      nanocrystals has also been evaluated by MTT assay, IC50 values, and histological
      analysis of lymphatic node sections.

PMID- 21742377
TI  - The sex-specific effects of famine on the association between placental size and
      later hypertension.
AB  - BACKGROUND: People who had low birth weight are at increased risk of
      hypertension. This may reflect fetal programming by undernutrition. Placental
      size is also associated with hypertension. Maternal undernutrition during the
      Dutch famine reduced placental surface area. We examined whether maternal
      undernutrition altered the relationship between placental size and later
      hypertension. METHODS: Retrospective cohort study among 860 subjects born in
      Amsterdam during 1943-47. 216 subjects were taking anti-hypertensive medication.
      Birth records included placental length and breadth from which we calculated its
      area. RESULTS: Among men who were not in utero during the famine hypertension was
      associated with a small placental surface area due to a small placental breadth,
      and with an oval-shaped surface. The OR for hypertension was 0.83 (95% CI 0.70 to
      1.00) for a 40 cm(2) increase in surface area. Among men who were in utero during
      the famine hypertension was associated with a large placental surface area due to
      a large placental breadth, and with a round-shaped surface. The OR for
      hypertension was 1.34 (95% CI 0.99 to 1.80) for a 40 cm(2) increase in surface
      area. The associations between placental size and hypertension in men who were
      and were not in utero during the famine were significantly different (p values
      for interaction = 0.008 for placental surface area, 0.001 for the breadth and
      0.01 for the difference in the two diameters). Among women hypertension was not
      associated with placental size. CONCLUSIONS: Our study provides the first direct
      evidence that changes in maternal diet during pregnancy alter the relationship
      between placental size and later hypertension among men but not women. We suggest
      that among men who were not in utero during the famine, hypertension was related
      to impaired implantation, whereas among men who were in utero during the famine
      it was related to compensatory expansion of the placental surface.

PMID- 21742379
TI  - Procalcitonin is a useful marker of infection in neutropenia.

PMID- 21742378
TI  - GVI phospholipase A2 role in the stimulatory effect of sphingosine-1-phosphate on
      TRPC5 cationic channels.
AB  - The Transient Receptor Potential Canonical 5 (TRPC5) protein forms calcium
      permeable cationic channels that are stimulated by G protein-coupled receptor
      agonists. The signaling pathways of such agonist effects are poorly understood.
      Here we investigated the potential for involvement of lysophosphatidylcholine
      (LPC) and arachidonic acid generated by group 6 (GVI) phospholipase A2 (PLA2)
      enzymes, focusing on stimulation of TRPC5 by sphingosine-1-phosphate (S1P) which
      acts via a pertussis toxin-sensitive (Gi/o protein) pathway without Ca2+-release.
      Experiments were on HEK 293 cells containing conditional expression of human
      TRPC5. Channel activity was recorded using an intracellular calcium indicator or
      whole-cell patch-clamp and PLA2 activity was detected using 3H-arachidonic acid.
      S1P stimulated PLA2 and TRPC5 activities. Both effects were suppressed by the GVI
      PLA2 inhibitor bromoenol lactone. Knock-down of GVI PLA2 by RNA interference
      suppressed channel activity evoked by S1P whereas activity evoked by the direct
      channel stimulator LPC was unaffected. Arachidonic acid did not stimulate the
      channels. Prior exposure of channels to LPC but not arachidonic acid suppressed
      channel activity evoked by S1P but not gadolinium, a putative direct stimulator
      of the channels. The data suggest roles of LPC and GVI PLA2 in S1P-evoked TRPC5
      activity.

PMID- 21742380
TI  - Identification of Porphyromonas gingivalis lipopolysaccharide-binding proteins in
      human saliva.
AB  - Porphyromonas gingivalis causes periodontal diseases and its lipopolysaccharide
      (LPS) is considered as a major virulence factor responsible for pathogenesis.
      Since initial recognition of P. gingivalis LPS (Pg.LPS) in the oral cavity might
      be crucial for the host response, we identified Pg.LPS-binding proteins (Pg.LPS
      BPs) using Pg.LPS-immobilized beads and a high-resolution mass spectrometry. LPS
      purified from P. gingivalis was conjugated onto N-hydroxysuccinimidyl
      Sepharose((r)) 4 Fast Flow beads. Notably, Pg.LPS-conjugated beads could
      stimulate Toll-like receptor 2 (TLR2) as determined by a TLR2-depdendent reporter
      expression system using CHO/CD14/TLR2. In addition, the Pg.LPS-conjugated beads
      induced the production of inflammatory mediators such as nitric oxide and
      interferon-gamma-inducible protein-10 in the macrophage cell-line, RAW 264.7.
      These results imply that Pg.LPS retained its immunological properties during the
      conjugation process. Then, the Pg.LPS-conjugated beads were mixed with a pool of
      saliva obtained from nine human subjects to capture Pg.LPS-BPs and molecular
      identities were determined by LTQ-Orbitrap hybrid fourier transform mass
      spectrometry. Pg.LPS-BPs captured at high frequencies included alpha-amylase,
      cystatin, prolactin-inducible protein, lysozyme C, immunoglobulin components,
      serum albumin, lipocalin-1, and submaxillary gland androgen-regulated protein 3B.
      These proteins are known to be involved in bacterial adhesion and colonization,
      anti-microbial functions or modulation of immune responses.

PMID- 21742381
TI  - Treatment-induced manic switch in the course of unipolar depression can predict
      bipolarity: cluster analysis based evidence.
AB  - BACKGROUND: Antidepressants are known to induce manic switch in patients with
      depression. Treatment-induced mania is not considered as bipolar disorder in DSM
      IV. The aim of this study was to assess whether clinical characteristics of
      patients with unipolar depression with a history of treatment-induced mania were
      similar to those of patients with bipolar disorder. METHOD: The study included
      217 consecutive patients with DSM-IV mood disorders, diagnosed as: bipolar
      disorder type I (BP-I, n = 58) or type II (BP-II, n = 18) whose first episodes
      were depression, recurrent (unipolar) major depressive disorder with a history of
      antidepressant treatment-induced mania (switchers = sUD; n = 61) and without such
      an event (rUD; n = 80). First, the groups were compared with regard to clinical
      features and course specifiers using variance and chi-square analysis. Variables
      that differed significantly between the four groups were included in two-step
      cluster analysis to explore naturally occurring subgroups in all diagnoses.
      Subsequently, the relationship between the naturally occurring clusters and pre
      defined DSM-IV diagnoses were investigated. RESULTS: Two-step cluster analysis
      revealed two different naturally occurring groups. Higher severity of depressive
      episodes, with higher rate of melancholic features, higher number of
      hospitalization and suicide attempts were represented in one cluster where
      switchers (77%), bipolar I (94.8%) and II (83.3%) patients clustered together.
      CONCLUSION: The findings of this study confirm that treatment-induced mania is a
      clinical phenomenon that belongs within the bipolar spectrum rather than a
      coincidental treatment complication, and that it should be placed under "bipolar
      disorders" in future classification systems. LIMITATIONS: The study includes the
      limitations of any naturalistic retrospective study.

PMID- 21742382
TI  - Fetal aorta wall inflammation in ultrasound-detected aortic intima/media
      thickness and growth retardation.
AB  - Several studies have reported that fetuses with intrauterine growth restriction
      (IUGR) and infants with low birth weight present increased intima/media thickness
      (aIMT) of the abdominal aorta wall compared with fetuses and infants appropriate
      for gestational age (AGA). Evidence suggested that aIMT might be related to
      inflammation, probably indicating a very early stage of future adulthood disease,
      such as atherosclerosis. We aimed to investigate histological findings in the
      abdominal aorta wall of one IUGR stillbirth in which ultrasound had detected
      aIMT. Microscopy observations of the abdominal aorta wall confirmed the intima
      thickening and detected condensation of the elastic fibers forming an evident
      internal elastic membrane and presence of inflammatory elements, such as
      macrophages, activated endothelial cells, and fibroblastoid cells. The present
      study highlights that IUGR associated with aIMT is related to inflammation, which
      might represent a very early sign of future adult lesions.

PMID- 21742383
TI  - The "Reading the Mind in the Eyes" test as a new way to explore complex emotions
      decoding in alcohol dependence.
AB  - It has been repeatedly shown that alcohol dependence is associated with emotional
      impairments, particularly for emotional facial expression decoding. Nevertheless,
      most earlier studies focused on basic emotions and did not explore more subtle
      affective states. In order to obtain a more accurate evaluation, and in view of
      earlier results showing impaired performance for this task among high-risk
      children of alcohol-dependent participants, the "Reading the Mind in the Eyes"
      test was used here to explore emotional recognition in alcohol dependence. We
      showed that the deficit described earlier for basic negative emotions is (1)
      generalizable to complex and positive emotions; and (2) specific for emotional
      features. This strengthens the proposition of a general face recognition
      impairment in alcohol dependence.

PMID- 21742384
TI  - Viral transcriptome analysis of feline immunodeficiency virus infected cells
      using second generation sequencing technology.
AB  - Feline immunodeficiency virus (FIV) is a widespread pathogen causing
      immunodeficiency in domestic cats and related wild cat species. The virus genome
      includes the main structural genes common to all retroviruses as well as
      accessory genes displaying essential functions during the viral life cycle.
      Expression of viral genes involves transcription of provirus genomes into full
      length transcripts, which are partially processed into several spliced mRNA
      variants for the translation of particular proteins. Among several FIV isolates
      derived from domestic cats, notable differences in pathogenicity could be
      observed leading to identification of low and high pathogenic virus isolates.
      This study investigates the viral transcriptome of two differentially virulent
      FIV strains using second generation sequencing (SGS) technology. The expression
      levels of viral genes as detected by SGS were additionally determined by reverse
      transcription quantitative PCR analysis in order to compare two methods of mRNA
      quantification. The different properties of both methods, especially regarding
      normalization between samples, had to be considered when comparing the resulting
      data. SGS turned out to be a suitable technique for comparing mRNA transcription
      between both FIV infected cell lines and the identification of spliced viral
      transcripts. In contrast to this, the quantification of these spliced isoforms
      using SGS data was impeded by the short length of sequencing reads. In summary,
      SGS analysis revealed very consistent mRNA levels for the majority of viral genes
      between the low pathogenic Petaluma and the more highly pathogenic Glasgow 8
      isolate. Notable differences among the two FIV strains could be observed in the
      viral mRNA splicing where Glasgow 8 displays similarities to the transcription
      pattern seen in the early stages of natural lentivirus infections. Thus,
      divergences in the regulation of post-transcriptional RNA processing might
      represent an additional contributor to the diverse pathogenic effects of
      individual FIV isolates. Taken together, this study aims to investigate the viral
      transcriptome as one part of the complex network of virus-host interactions,
      which will contribute to gaining deeper insights into FIV pathogenesis.

PMID- 21742385
TI  - No influence on disease progression of non-HLA susceptibility genes in MS.
AB  - Recently, several non-HLA loci have been shown to be convincingly associated with
      Multiple Sclerosis (MS) susceptibility, assumingly indicating important pathways
      in the pathogenesis. A genotype influence on disease outcome measures by these
      genes would support a role of these pathways in ongoing tissue damage. Here,
      however, we report a consistent dissociation between causation and progression
      for five non-HLA genotypes (IL7R, IL2RA, CLEC16A, CD226 and SH2B3) in 1776
      Scandinavian MS patients.

PMID- 21742386
TI  - Differential expression of muscarinic acetylcholine receptor subtypes in Jurkat
      cells and their signaling.
AB  - Muscarinic acetylcholine receptors expression and signaling in the human Jurkat T
      cell line were investigated. Semiquantitative real-time PCR and radioligand
      binding studies, using a wide set of antagonist compounds, showed the co
      existence of M(3), M(4), and M(5) subtypes. Stimulation of these subpopulations
      caused a concentration and time- dependent activation of second messengers and
      ERK signaling pathways, with a major contribution of the M(3) subtype in a
      G(q/11)-mediated response. In addition, we found that T-cell stimulation leads to
      increased expression of M(3) and M(5) both at transcriptional and protein levels
      in a PLC/PKCtheta dependent manner. Our data clarifies the functional role of
      AChR subtypes in Jurkat cells and pave the way to future studies on the potential
      cross-talk among these subpopulations and their regulation of T lymphocytes
      immune function.

PMID- 21742387
TI  - Subglottic stenosis: another challenge for intubation and potential mechanism of
      airway obstruction in Pierre Robin Sequence.
AB  - OBJECTIVE: To determine the endotracheal tube (ETT) size and presence of
      subglottic narrowing in children less than 1 year old with Pierre Robin Sequence
      (PRS). MATERIALS AND METHODS: We performed a retrospective review from 2005 to
      2009 of infants with PRS who underwent diagnostic laryngoscopy (DL) and
      intubation. RESULTS: Fifteen children with a median age of 25 days were reviewed.
      All patients, except one, were born full term. Subglottic narrowing was
      visualized in 5 patients (33%). 73% of all patients required an ETT size smaller
      than what is recommended by intubation guidelines in the literature in regards to
      normative data based on age and weight. CONCLUSION: Infants with PRS may have a
      higher incidence of subglottic stenosis and require a smaller ETT compared to the
      normal population. This pilot study warrants a larger prospective investigation
      to validate these findings.

PMID- 21742388
TI  - More than being protective: functional roles for TGF-beta/activin signaling
      pathways at central synapses.
AB  - It is becoming increasingly clear that members of the transforming growth factor
      beta (TGF-beta) family have roles in the central nervous system that extend
      beyond their well-established roles as neurotrophic and neuroprotective factors.
      Recent findings have indicated that the TGF-beta signaling pathways are involved
      in the modulation of both excitatory and inhibitory synaptic transmission in the
      adult mammalian brain. In this review, we discuss how TGF-beta, bone
      morphogenetic protein and activin signaling at central synapses modulate synaptic
      plasticity, cognition and affective behavior. We also discuss the implications of
      these findings for the molecular understanding and potential treatment of
      neuropsychiatric diseases, such as anxiety, depression and other neurological
      disorders.

PMID- 21742390
TI  - Myocardial infiltration in Gaucher's disease detected by cardiac MRI.

PMID- 21742389
TI  - An opportunistic theory of cellular and systems consolidation.
AB  - Memories are often classified as hippocampus dependent or independent, and sleep
      has been found to facilitate both, but in different ways. In this Opinion, we
      explore the optimal neural state for cellular and systems consolidation of
      hippocampus-dependent memories that benefit from sleep. We suggest that these two
      kinds of consolidation, which are ordinarily treated separately, overlap in time
      and jointly benefit from a period of reduced interference (during which no new
      memories are formed). Conditions that result in reduced interference include slow
      wave sleep (SWS), NMDA receptor antagonists, benzodiazepines, alcohol and
      acetylcholine antagonists. We hypothesize that the consolidation of hippocampal
      dependent memories might not depend on SWS per se. Instead, the brain
      opportunistically consolidates previously encoded memories whenever the
      hippocampus is not otherwise occupied by the task of encoding new memories.

PMID- 21742391
TI  - Speckle tracking echocardiography in childhood myocarditis: spontaneous reversal
      of severe left ventricular rotational abnormalities during follow-up.

PMID- 21742392
TI  - Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers
      for head and neck cancer.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD) in a phase I trial on
      adaptive dose-painting-by-numbers (DPBN) for non-metastatic head and neck cancer.
      MATERIALS AND METHODS: Adaptive intensity-modulated radiotherapy was based on
      voxel intensity of pre-treatment and per-treatment [(18)F]fluoro-2-deoxy-d
      glucose positron emission tomography ((18)F-FDG-PET) scans. Dose was escalated to
      a median total dose of 80.9 Gy in the high-dose clinical target volume (dose
      level I) and 85.9 Gy in the gross tumor volume (dose level II). The MTD would be
      reached, if >= 33% of patients developed any grade >= 4 toxicity (DLT) up to 3
      months follow-up. RESULTS: Between February 2007 and August 2009, seven patients
      at dose level I and 14 at dose level II were treated. All patients completed
      treatment without interruption. At a median follow-up for surviving patients of
      38 (dose level I) and 22 months (dose level II) there was no grade >= 4 toxicity
      during treatment and follow-up but six cases of mucosal ulcers at latency of 4-10
      months, of which five (36%) were observed at dose level II. Mucosal ulcers healed
      spontaneously in four patients. CONCLUSIONS: Considering late mucosal ulcers as
      DLT, the MTD of a median dose of 80.9 Gy has been reached in our trial.

PMID- 21742393
TI  - The effect of alternative biological modelling parameters (alpha/beta and half
      time of repair T 1/2 ) on reported EQD2 values in the treatment of advanced
      cervical cancer.
AB  - PURPOSE: To evaluate the effect of different alpha/beta and half-time of repair
      T(1/2) on the assessment of clinical treatment plans for patients with cervical
      cancer. MATERIALS AND METHODS: We used EBRT and BT treatment plans of five
      patients, planned with MRI guided BT. We computed 3D EQD2 dose distributions of
      combined EBRT and BT treatments and calculated D90 of high-risk clinical target
      volume (HR-CTV) and D(2cc) for bladder and rectum, and the ratio
      D(2cc)(bladder)/D90(HR-CTV). BT was modelled as PDR (two applications of
      32*60cGy) and HDR (two applications of 2*7Gy). We assumed a low, standard and
      high value for the biological parameters: HR-CTV alpha/beta=5/10/15Gy and
      T(1/2)=0.5/1.5/2.5h; OAR alpha/beta=2/3/4Gy; T(1/2)=0.5/1.5/4.5h. RESULTS: The
      chosen variation in modelling parameters had a much larger effect on PDR
      treatments than on HDR treatments, especially for OAR, thus creating larger
      uncertainties. The relative mean range of the ratio D(2cc)(bladder)/D90(HR-CTV)
      is 72% for PDR and 25% for HDR. Out of the 125 modelled combinations 48 PDR plans
      and 23 HDR plans comply with clinical objectives. CONCLUSION: For HDR
      brachytherapy, only alpha/beta has a significant impact on reported EQD2 values,
      whereas for PDR both alpha/beta and T(1/2) are important. Generally, the ratio
      D(2cc)(bladder)/D90(HR-CTV) is more favourable for PDR, even considering the
      larger uncertainties in EQD2.

PMID- 21742394
TI  - Production of bioactive substances by intestinal bacteria as a basis for
      explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid.
AB  - The mechanisms by which intestinal bacteria achieve their associated health
      benefits can be complex and multifaceted. In this respect, the diverse microbial
      composition of the human gastrointestinal tract (GIT) provides an almost
      unlimited potential source of bioactive substances (pharmabiotics) which can
      directly or indirectly affect human health. Bacteriocins and fatty acids are just
      two examples of pharmabiotic substances which may contribute to probiotic
      functionality within the mammalian GIT. Bacteriocin production is believed to
      confer producing strains with a competitive advantage within complex microbial
      environments as a consequence of their associated antimicrobial activity. This
      has the potential to enable the establishment and prevalence of producing strains
      as well as directly inhibiting pathogens within the GIT. Consequently, these
      antimicrobial peptides and the associated intestinal producing strains may be
      exploited to beneficially influence microbial populations. Intestinal bacteria
      are also known to produce a diverse array of health-promoting fatty acids.
      Indeed, certain strains of intestinal bifidobacteria have been shown to produce
      conjugated linoleic acid (CLA), a fatty acid which has been associated with a
      variety of systemic health-promoting effects. Recently, the ability to modulate
      the fatty acid composition of the liver and adipose tissue of the host upon oral
      administration of CLA-producing bifidobacteria and lactobacilli was demonstrated
      in a murine model. Importantly, this implies a potential therapeutic role for
      probiotics in the treatment of certain metabolic and immunoinflammatory
      disorders. Such examples serve to highlight the potential contribution of
      pharmabiotic production to probiotic functionality in relation to human health
      maintenance.

PMID- 21742395
TI  - A novel genotyping scheme for Vibrio parahaemolyticus with combined use of large
      variably-presented gene clusters (LVPCs) and variable-number tandem repeats
      (VNTRs).
AB  - A total of 18 variably-presented gene clusters (LVPCs) and nine previously
      characterized variable-number tandem repeats (VNTRs), and all known virulence
      markers were screened for their frequency and/or copy number in 251 global
      strains of Vibrio parahaemolyticus using PCR and gel or capillary
      electrophoresis. A two-step genotyping approach combining the use of LVPCs and
      VNTRs was established accordingly. The frequency profiles of LVPCs and virulence
      markers were primarily used to group the strains into six distinct complexes with
      different potential pathogenicity natures. The strains from each of these
      complexes were further analyzed with VNTRs to give a much more detailed
      discrimination of the strains. A genetic fingerprint-like database of a large
      collection of strains established with this two-stage approach would be very
      useful for identification, genotyping, origin tracing, and risk estimation of V.
      parahaemolyticus.

PMID- 21742396
TI  - Diabetic dyslipidaemia in Asian populations in the Western Pacific Region: what
      we know and don't know.
AB  - Approximately 77 million persons with diabetes reside in the Western Pacific
      Region. This number is estimated to rise to 113 million in 2030 with increasing
      burden of cardio-renal disease, affecting an increasingly young population.
      Randomized clinical trials have confirmed the benefits of using statins to reduce
      low-density lipoprotein cholesterol in preventing cardiovascular disease (CVD) in
      Caucasians, although similar data are lacking in Asia. Experts from the Western
      Pacific Region met and reviewed evidence regarding risk association of diabetic
      dyslipidaemia with cardio-renal disease, effects of lipid lowering, recommended
      guidelines and clinical practices in Asian populations. There is strong evidence
      supporting the role of diabetic dyslipidaemia in cardio-renal disease and the
      benefits of lipid lowering in these populations. The high rate of diabetic kidney
      disease, its close links with CVD, and the benefits of lipid lowering on renal
      function are particularly relevant to this population. While most national
      guidelines use criteria similar to the West in management of diabetic
      dyslipidaemia, there are consistently low rates of use of lipid-lowering drugs
      and attaining treatment goals in the region. The group recommends conducting
      randomized studies, strengthening of the health care system to promote early
      detection, and intervention of diabetic dyslipidaemia to prevent end organ
      damage.

PMID- 21742397
TI  - Successful treatment with continuous subcutaneous insulin infusion for allergy to
      human insulin and its analogs.
AB  - Allergy to insulin is rare. We report a type 2 diabetic patient who is allergic
      to human insulin and its analog preparations and successful treatment with
      continuous subcutaneous insulin infusion.

PMID- 21742398
TI  - Diabetes prevalence and determinants in Indigenous Australian populations: A
      systematic review.
AB  - AIMS: To perform a systematic review of the prevalence of diabetes and impaired
      glucose tolerance (IGT) in Indigenous Australians in order to clarify overall
      patterns, by determinants such as age, gender, region, ethnicity and remoteness.
      METHODS: The OVID interface to Medline and the Australian Indigenous
      HealthInfoNet databases were systematically searched from years 1997 to 2010.
      Studies reporting diabetes prevalence were included if they used population-based
      samples of Indigenous Australians. Diagnosis of diabetes was based on self-report
      or standard diagnostic criteria. RESULTS: Twenty-four studies were included. The
      diabetes prevalence ranged from 3.5 to 33.1%; IGT estimates ranged from 4.7 to
      21.1%. Prevalence was greater among Indigenous Australian women compared to men,
      the Northern Territory's Top End compared to Central Australia, Torres Strait
      Islanders compared to Aboriginals, older (>=35 years) compared to younger (<35
      years) age groups, and remote compared to urban settings. Patterns of IGT
      prevalence were similar to those observed for diabetes. CONCLUSIONS: Although the
      prevalence of diabetes and IGT is high, there appears to be considerable
      variation in prevalence between different segments of the Australian Indigenous
      population. Data on diabetes prevalence in the urban Australian Indigenous
      population is lacking, despite accounting for almost three quarters of the total
      population.

PMID- 21742399
TI  - The relationship between visfatin and HOMA-IR in hypertensive patients, and the
      effect of antihypertensive drugs on visfatin and HOMA-IR in hypertensive patients
      with insulin resistance.
AB  - OBJECTIVE: To investigate the correlation between serum visfatin and insulin
      resistance (IR) in non-diabetic essential hypertensive (EH) patients with and
      without IR, and to evaluate the effect of antihypertensive treatment on serum
      visfatin and IR in these patients. METHODS: A total of 81 non-diabetic EH
      patients, including 54 with IR and 27 without IR, were enrolled. After two weeks
      wash-out, patients with IR were randomly assigned to telmisartan (group T) or
      amlodipine (group A) for 6 months. Blood samples were taken before and after
      treatment for measurement of routine biochemical parameters, visfatin and insulin
      resistance (measured by HOMA-IR). RESULTS: Visfatin was independently correlated
      with HOMA-IR (r=0.845, P=0.000). After 6 months of treatment, both drugs lowered
      HOMA-IR, more significantly so in group T than group A (P=0.010). Serum visfatin
      levels increased in group T but decreased in group A. CONCLUSION: Serum visfatin
      levels were higher in non-diabetic EH patients with IR compared with those
      without IR. Visfatin is independently correlated with HOMA-IR. Telmisartan lowers
      HOMA-IR to a greater extent than amlodipine. Interestingly, serum visfatin
      increased with telmisartan yet decreased with amlodipine treatment.

PMID- 21742400
TI  - Molecular changes in diabetic foot ulcers.
AB  - AIM: This study investigated the molecular changes of extracorporeal shockwave
      therapy (ESWT) and hyperbaric oxygen therapy (HBOT) in chronic diabetic foot
      ulcers. METHODS: A cohort study consisted of 39 patients (44 ulcers) in the ESWT
      group and 38 patients (40 ulcers) in the HBOT group with similar demographic
      characteristics. The ESWT group received shockwave therapy twice per week for
      total six treatments. The HBOT group received hyperbaric oxygen therapy daily for
      total 20 treatments. Biopsy was performed from the periphery of the ulcer before
      and after treatment. The specimens were immuno-stained, and the positive immuno
      activities of vWF, VEGF, eNOS, PCNA, EGF and TUNEL expressions were examined and
      quantified microscopically. RESULTS: Significant increases in vWF, VEGF, eNOS,
      PCNA and EGF expressions and a decrease in TUNEL expression were noted after ESWT
      (P<0.05), whereas the changes after HBOT were statistically not significant
      (P>0.05). The differences of vWF, VEGF, eNOS, PCNA, EGF and TUNEL expressions
      between the two groups were comparable before treatment (P>0.05), however, the
      differences became statistically significant after treatment (P<0.05) favoring
      the ESWT group. CONCLUSION: ESWT showed significant increases in angiogenesis and
      tissue regeneration over HBOT in diabetic foot ulcers.

PMID- 21742401
TI  - Does cerebral small vessel disease predict future decline of cognitive function
      in elderly people with type 2 diabetes?
AB  - AIMS: We conducted a 3-year longitudinal study concerning an association between
      cognitive function and cerebral small vessel disease (SVD) seen on magnetic
      resonance imaging (MRI) in elderly type 2 diabetic patients. METHODS: Four
      cognitive function tests--MMSE, word recall, Digit Symbol Substitution (DSS), and
      Stroop Color Word (Stroop)--were performed in 67 diabetic patients twice in 2006
      and 2009. SVD was diagnosed as silent brain infarct (SBI) and white matter
      lesions (WMLs) according to MRI. RESULTS: Number of SBI was significantly
      correlated with a decline in DSS and Stroop tests, while WMLs grade was only
      associated with it in DSS tests after adjustment for age, gender, education
      years, the presence of hypertension and dyslipidemia, and smoking. Severity of
      SVD at baseline was stronger associated with cognitive function after the 3-year
      follow-up than at baseline. WMLs progression was associated with more rapid
      decline of DSS tests compared to a group without progression. CONCLUSIONS: SVD
      seen on MRI is a good marker for predicting future cognitive decline, and
      monitoring of treatment through the use of such markers is expected to maintain a
      good quality of life for elderly diabetic patients.

PMID- 21742403
TI  - Targeting Syk-Card9-activating C-type lectin receptors by vaccine adjuvants:
      findings, implications and open questions.
AB  - Pathogen recognition by the innate immune system is essential for the induction
      of adaptive T cell responses. A diverse range of pathogen-associated molecular
      patterns (PAMPs) are recognized by a variety of pathogen recognition receptors
      (PRRs). Among these are the well known Toll-like receptors (TLR) and the more
      recently described C-type lectin receptors (CLR) which utilize distinct signaling
      pathways leading to a diverse repertoire of effector molecules produced. The
      composition of the inflammatory juice released from activated innate immune cells
      has a major impact on the polarization of Th cell responses. Defined PAMPs may
      therefore be used as adjuvants to direct adaptive immune responses to subunit
      vaccines. Targeting CLR is an alternative or complementary strategy to TLR
      triggering adjuvants that will benefit the development of more efficient subunit
      vaccines for prevention of major human infectious diseases. In this short review,
      we discuss the potential of CLRs activating APC via the Syk-Card9 pathway as
      receptors for adjuvants that direct the development of robust Th17 and Th1
      responses to subunit vaccines.

PMID- 21742404
TI  - Novel roles of complement in T effector cell regulation.
AB  - Our understanding of the complement system has markedly evolved from its early
      beginnings as a protein system merely detecting and tagging a pathogen for
      further clearance. For example, the repertoire of danger that complement
      recognizes covers currently a wide range of distinct self and non-self danger
      signals. Further, complement is now firmly established as instructor of adaptive
      B and T cell immunity. This review focuses on two the recent emerging paradigms
      in the field. Firstly, that complement is not only vitally required for the
      induction of Th1 immunity but also for the timely contraction of this protective
      response and therefore for prevention of autoimmunity and immune homeostasis.
      Secondly, that local rather than systemic complement is impacting on immune
      modulation during a T cell response.

PMID- 21742406
TI  - Interleukin-18-mediated interferon-gamma secretion is regulated by thymosin beta
      4 in human NK cells.
AB  - Thymosin beta 4 (Tbeta4) is the major G-actin sequestering molecule and is
      abundant in lymphoid tissues. However, it is not clear what regulates Tbeta4
      expression and what its function is on natural killer (NK) cells. We investigated
      whether interleukin-18 (IL-18) has a role in Tbeta4 expression and if enhanced
      Tbeta4 influences IL-18-mediated interferon-gamma (IFN-gamma) secretion. In this
      study, recombinant human IL-18 (rhIL-18) enhanced the endogenous level of Tbeta4
      through p38MAPK and JNK signaling pathway in the human NK cell line, NK-92MI.
      Overexpression of endogeneous Tbeta4 stimulated IFN-gamma expression and
      secretion. Additionally, pretreatment with an inhibitor for Tbeta4 decreased IL
      18-enhanced IFN-gamma secretion, and transfection with Tbeta4-specific short
      hairpin RNA resulted in reduction of IFN-gamma production in primary NK cells as
      well as in the human NK cell line. Taken together, these data indicated that
      Tbeta4 is regulated by IL-18 and is involved in IL-18-enhanced IFN-gamma
      secretion in NK cells.

PMID- 21742405
TI  - CD46 processing: a means of expression.
AB  - CD46 is a ubiquitously expressed type I transmembrane protein, first identified
      as a regulator of complement activation, and later as an entry receptor for a
      variety of pathogens. The last decade has also revealed the role of CD46 in
      regulating the adaptive immune response, acting as an additional costimulatory
      molecule for human T cells and inducing their differentiation into Tr1 cells, a
      subset of regulatory T cells. Interestingly, CD46 regulatory pathways are
      defective in T cells from patients with multiple sclerosis, asthma and rheumatoid
      arthritis, illustrating its importance in regulating T cell homeostasis. Indeed,
      CD46 expression at the cell surface is tightly regulated in many different cell
      types, highlighting its importance in several biological processes. Notably, CD46
      is the target of enzymatic processing, being cleaved by metalloproteinases and by
      the presenilin/gamma secretase complex. This processing is required for its
      functions, at least in T cells. This review will summarize the latest updates on
      the regulation of CD46 expression and on its effects on T cell activation.

PMID- 21742407
TI  - The Arabidopsis thaliana cysteine-rich receptor-like kinase CRK20 modulates host
      responses to Pseudomonas syringae pv. tomato DC3000 infection.
AB  - In plants, the cysteine-rich repeat kinases (CRKs) are a sub-family of receptor
      like protein kinases that contain the DUF26 motif in their extracellular domains.
      It has been shown that in Arabidopsis thaliana, CRK20 is transcriptionally
      induced by pathogens, salicylic acid and ozone (O(3)). However, its role in
      responses to biotic and abiotic stress remains to be elucidated. To determine the
      function of CRK20 in such responses, two CRK20 loss-of-function mutants, crk20-1
      and crk20-2, were isolated from public collections of Arabidopsis T-DNA tagged
      lines and examined for responses to O(3) and Pseudomonas syringae pv. tomato
      (Pst) DC3000. crk20-1 and crk20-2 showed similar O(3) sensitivities and no
      differences in the expression of defense genes when compared with the wild-type.
      However, pathogen growth was significantly reduced, while there were no
      differences in the induction of salicylic acid related defense genes or salicylic
      acid accumulation. Furthermore, correlation analysis of CRK20 gene expression
      suggests that it has a role in the control of H(2)O and/or nutrient transport. We
      therefore propose that CRK20 promotes conditions that are favorable for Pst
      DC3000 growth in Arabidopsis, possibly through the regulation of apoplastic
      homeostasis, and consequently, of the environment of this biotrophic pathogen.

PMID- 21742408
TI  - In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot
      study.
AB  - BACKGROUND: Dysplastic nevi are thought to be precursors of melanoma during a
      stepwise process. However, this concept is still controversial and precise
      correlation between clinical and histopathologic features is lacking. In vivo
      confocal microscopy represents a noninvasive imaging technique producing
      horizontal sections at nearly histopathologic resolution. OBJECTIVE: We sought to
      determine whether specific histologic features in dysplastic nevi have reliable
      correlates on confocal microscopy and to develop an in vivo microscopic grading
      system. METHODS: Sixty melanocytic lesions with equivocal dermatoscopic aspects,
      corresponding to 19 nondysplastic nevi, 27 dysplastic nevi, and 14 melanomas,
      were analyzed by confocal microscopy and histopathology, using the Duke grading
      criteria. RESULTS: All architectural and cytologic features of the Duke grading
      score had significant reflectance confocal microscopy correlates. Confocally,
      dysplastic nevi were characterized by a ringed pattern, in association with a
      meshwork pattern in a large proportion of cases, along with atypical junctional
      cells in the center of the lesion, and irregular junctional nests with short
      interconnections. A simplified algorithm was developed to distinguish dysplastic
      nevi from melanoma and nondysplastic nevi. The contemporary presence of cytologic
      atypia and of atypical junctional nests (irregular, with short interconnections,
      and/or with nonhomogeneous cellularity) was suggestive of histologic dysplasia,
      whereas a widespread pagetoid infiltration, widespread cytologic atypia at the
      junction, and nonedged papillae suggested melanoma diagnosis. LIMITATIONS: A
      small number of cases were evaluated because of the necessity to analyze numerous
      histopathologic and confocal features. CONCLUSION: The possibility to detect
      dysplastic nevi in vivo may lead to an appropriate management decision.

PMID- 21742409
TI  - Prevalence of self-report photosensitivity in cutaneous lupus erythematosus.
AB  - BACKGROUND: Little is known about the prevalence of self-reported
      photosensitivity (PS) and its effects on quality of life in a US cutaneous lupus
      population. OBJECTIVE: We sought to determine the prevalence of self-reported PS
      among a cutaneous lupus population and to examine its impact on quality of life.
      METHODS: A total of 169 patients with lupus were interviewed about PS symptoms
      and completed the modified Skindex-29+3, a quality-of-life survey. A complete
      skin examination was conducted and the Cutaneous Lupus Erythematosus Disease Area
      and Severity Index was completed. RESULTS: In all, 68% of patients reported some
      symptoms of PS. The PS group (those who reported a history of and current PS)
      scored worse on PS-related items of the modified Skindex-29+3 and had higher
      cutaneous disease activity as determined by the Cutaneous Lupus Erythematosus
      Disease Area and Severity Index. Patients with PS had worse symptoms and emotions
      and experienced significant functional impairments compared with patients who had
      cutaneous lupus without PS. LIMITATIONS: This study was done at a single referral
      center. CONCLUSIONS: Self-reported PS is very common among patients with
      cutaneous lupus and is associated with significant impairments related to
      symptoms, emotions, and daily functioning.

PMID- 21742410
TI  - Compliance with sunscreen advice in a survey of adults engaged in outdoor winter
      recreation at high-elevation ski areas.
AB  - BACKGROUND: Adults are advised to wear sunscreen with a sun protection factor
      (SPF) of 15 or higher, apply it up to 30 minutes before sun exposure, and reapply
      it after 2 hours to reduce exposure to ultraviolet radiation in sunlight for the
      prevention of skin cancer. OBJECTIVE: This study investigated the extent to which
      adults comply with sunscreen advice. METHODS: A survey was conducted with 4837
      adult skiers and snowboarders at 28 high-altitude ski areas in western North
      America in January through April 2001 through 2002. Respondents self-reported use
      of sunscreen, its SPF, time of first application, and reapplication. RESULTS:
      Only 4.4% (95% confidence interval [CI] = +/-0.6) of adults were in full
      compliance with all sunscreen advice. Half (49.8% [95% CI = +/-1.4]) complied
      with SPF 15 or higher advice. Of those wearing sunscreen, 73.2% (95% CI = +/-1.8)
      applied the sunscreen 30 minutes before beginning skiing/snowboarding, but only
      20.4% (95% CI = +/-2.0) complied with advice to reapply it after 2 hours. Total
      compliance was lowest during inclement weather, on low-ultraviolet days, by men,
      and among respondents who believed skin cancer was unimportant and with low sun
      sensitive skin. It was positively associated with wearing lip balm and hats with
      a brim. LIMITATIONS: The sample was predominantly male and of high socioeconomic
      status; the results apply most to winter recreation when ultraviolet radiation
      levels are low, and sunscreen use was assessed by self-report. CONCLUSION:
      Although the recommendation to use SPF 15 or higher sunscreen has reached many
      adults, the reapplication advice is heeded by few adults and needs to be
      highlighted in future sun safety promotions.

PMID- 21742411
TI  - Psoriasis and cardiovascular risk factors: a case-control study on inpatients
      comparing psoriasis to dermatitis.
AB  - BACKGROUND: Previous reports demonstrated an association between psoriasis and
      cardiovascular disease (CVD) risk factors. However, most of these studies were
      based on computerized databases of outpatient clinics, which, because of
      International Classification of Diseases, Ninth Revision coding issues, require
      validation of the diagnosis of psoriasis. OBJECTIVE: We sought to study
      associations between psoriasis and CVD risk factors among psoriatic inpatients
      compared to inpatients with dermatitis. METHODS: A case-control study was
      performed using computerized medical databases from the Department of Dermatology
      at Rabin Medical Center in Israel. Inpatients given the diagnosis of psoriasis
      were compared with inpatients given the diagnosis of forms of dermatitis for the
      prevalence of smoking, obesity, diabetes, hypertension, hyperlipidemia, and CVD.
      Logistic regression models were used for multivariate analyses. RESULTS: The
      study included 1079 inpatients with psoriasis and 1079 age- and gender-matched
      inpatients with dermatitis (control patients). A multivariate logistic regression
      model demonstrated that psoriasis is an independent risk factor for diabetes
      (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.17-1.75), hypertension (OR
      1.31; 95% CI 1.09-1.58), obesity (OR 1.32; 95% CI 0.99-1.76), and smoking (OR
      1.38; 95% CI 1.10-1.73). Development of CVD was not significantly associated with
      psoriasis when correcting for diabetes, obesity, and hypertension. LIMITATIONS:
      Our study group was composed of inpatients only, which may be biased toward more
      elderly patients with severe psoriasis who may have consumed systemic treatment
      including immunosuppressants. CONCLUSIONS: Our study supports previous reports of
      an association between psoriasis and CVD risk factors, suggesting that the
      inflammatory process in psoriasis, but not in dermatitis, may have a systemic
      impact resulting in development of CVD risk factors.

PMID- 21742412
TI  - Are sunscreens luxury products?
AB  - BACKGROUND: The incidence of skin cancers is rapidly increasing in Western
      countries. One of the main sun-protection measures advocated is application of
      sunscreen. Some studies report a failure to comply with sunscreen application
      guidance. One explanation is their cost. OBJECTIVE: To evaluate the true cost of
      sunscreen in two situations: a 4-member family spending 1 week at the beach and a
      transplant patient respecting all the sun protection recommendations. METHODS: We
      performed an analysis of prices of sunscreens sold via Internet drugstores in
      Europe and North America. Standard sunscreen application recommendations were
      followed. We tested the recommended amount of sunscreen to be applied (ie, 2
      mg/cm(2)). RESULTS: Six hundred seven sunscreens from 17 drugstores in 7
      countries were evaluated. Median price of sunscreen was $1.7 US per 10 grams. The
      price decreased with the size of the bottle. The median price for a family varied
      from $178.2 per week to $238.4 per week. The price decreased by 33% if the family
      wore UV-protective T-shirts and by 41% if large-volume bottles were used. The
      median price for a transplant patient varied from $245.3 per year to $292.3 per
      year. LIMITATIONS: Anti-UVA activity and topical properties were not evaluated.
      We tested the recommended amount (2 mg/cm(2)) rather than the amount actually
      used (1 mg/cm(2)). CONCLUSION: Under acute sun exposure conditions (a week at the
      beach), the cost of sun protection appears acceptable if sun protective clothing
      is worn and large-format bottles and low-cost sunscreens are used. Conversely, in
      a sun-sensitive population requiring year-round protection, the annual budget is
      relatively high and patients may require financial assistance to be compliant
      with sun protection guidelines.

PMID- 21742413
TI  - Automated detection of nosocomial infections: evaluation of different strategies
      in an intensive care unit 2000-2006.
AB  - The aim of this study was to evaluate seven different strategies for the
      automated detection of nosocomial infections (NIs) in an intensive care unit
      (ICU) by using different hospital information systems: microbiology database,
      antibiotic prescriptions, medico-administrative database, and textual hospital
      discharge summaries. The study involved 1,499 patients admitted to an ICU of the
      University Hospital of Lyon (France) between 2000 and 2006. The data were
      extracted from the microbiology laboratory information system, the clinical
      information system on the ward and the medico-administrative database. Different
      algorithms and strategies were developed, using these data sources individually
      or in combination. The performances of each strategy were assessed by comparing
      the results with the ward data collected as a national standardised surveillance
      protocol, adapted from the National Nosocomial Infections Surveillance system as
      the gold standard. From 1,499 patients, 282 NIs were reported. The strategy with
      the best sensitivity for detecting these infections using an automated method was
      the combination of antibiotic prescription or microbiology, with a sensitivity of
      99.3% [95% confidence interval (CI): 98.2-100] and a specificity of 56.8% (95%
      CI: 54.0-59.6). Automated methods of NI detection represent an alternative to
      traditional monitoring methods. Further study involving more ICUs should be
      performed before national recommendations can be established.

PMID- 21742414
TI  - Evaluation of different methods to recover meticillin-resistant Staphylococcus
      aureus from hospital environmental surfaces.
AB  - The environment is implicated as a source of healthcare-associated infections
      (HAIs) and there is a need for evidence-based approaches to environmental
      sampling to assess cleanliness and improve infection prevention and control. We
      assessed, in vitro, different approaches to sampling the environment for
      meticillin-resistant Staphylococcus aureus (MRSA). In a laboratory-based
      investigation, the recovery of MRSA from two common hospital environments using
      six different sampling methods was evaluated, with a wild-type strain of MRSA. A
      100 cm(2) section of mattress and a laboratory bench surface were contaminated
      with known inocula of MRSA. Bacteria were recovered by sampling at 30 min after
      inoculation, using either saline-moistened cotton swabs, neutralising buffer
      swabs, eSwabs or macrofoam swabs, which were all enriched in tryptone soya broth,
      or by sampling with direct contact plates or chromogenic 'sweep' plates. The
      sensitivity (i.e. the minimum number of bacteria inoculated on to a surface which
      subsequently produced a positive result) of each method was determined for each
      surface. The most sensitive methods were eSwabs and macrofoam swabs, requiring
      6.1 * 10(-1) and 3.9 * 10(-1) MRSA/cm(2), respectively, to produce a positive
      result from the bench surface. The least sensitive swabbing method was saline
      moistened cotton swabs, requiring 1.1 * 10(3) MRSA/cm(2) of mattress. The
      recovery of bacteria from environmental samples varies with the swabs and
      methodology used and negative culture results do not exclude a pathogen-free
      environment. Greater standardisation is required to facilitate the assessment of
      cleanliness of healthcare environments.

PMID- 21742415
TI  - Lack of detectable diffuse or neuritic plaques and neurofibrillary tangles in the
      brains of aged hamsters.
AB  - Syrian golden hamsters (Mesocricetus auratus) are facultative hibernators with a
      life expectancy of approximately 2 years. Previous investigations showed a
      hyperphosphorylation of the tau protein during hibernation and aging and raised
      hopes that Syrian hamsters might represent a useful animal model to study
      pathogenetic mechanisms of Alzheimer's disease. Brain and spinal cord transversal
      sections of 190 hamsters 1-36 months of age were investigated using histology and
      immunohistochemistry to detect neurofibrillary tangles and/or diffuse as well as
      neuritic plaques. Summarized, amyloid deposition, neurofibrillary tangles, and
      diffuse as well as neuritic plaques were absent indicating that the Syrian golden
      hamster does not develop changes characteristic of Alzheimer's disease even at
      advanced age and does not represent an appropriate animal model for this disease.

PMID- 21742416
TI  - [Complications and nerve preservation in prostatectomy according to the time
      interval from diagnostic biopsy].
AB  - OBJECTIVES: To summarize the available evidence on complications and bilateral
      nerve preservation in radical prostatectomy in patients according to the time
      interval from diagnostic biopsy (more or less than six weeks). MATERIAL AND
      METHODS: Relevant studies were identified by using structured and specific search
      strategies for each of the databases consulted, without limitations. The
      methodological quality of each of the studies included was evaluated and the data
      were extracted independently. RESULTS: For open radical prostatectomy, two of the
      studies concluded that a time interval of less than 4 or 6 weeks between prostate
      biopsy and surgery had no influence on the postsurgical complications rate or on
      nerve preservation during surgery. For laparoscopic robotic-assisted radical
      prostatectomy, the study included concluded that performing this type of
      intervention in an interval of less than 4 or 6 weeks after diagnostic biopsy was
      associated with a higher risk of postsurgical complications. However, all these
      studies had major methodological limitations. CONCLUSIONS: The time interval
      between diagnostic biopsy and open surgery has no influence on the complications
      rate or nerve preservations. In contrast, an interval of less than 4 weeks
      between diagnostic biopsy and laparoscopic surgery is associated with a higher
      risk of surgical complications.

PMID- 21742417
TI  - [Relationships between sex hormone levels in men over 50 years of age and body
      composition, bone quality, and quality of life].
AB  - OBJECTIVE: To determine whether there was a relationship between sex hormone
      levels and body composition, bone health, and health-related quality of life in
      men over 50 years of age. MATERIAL AND METHODS: Transversal study carried out in
      230 Spanish male outpatients. Body composition was studied using direct
      anthropometric measures: height, weight, waistline circumference, dominant arm
      circumference, tricipital skinfold, dominant arm skinfold, subscapular skinfold.
      Calculated anthropometric parameters were obtained. Quantitative ultrasound
      measurements of the calcaneus were performed and bone turnover markers were
      determined (N-telopeptides urinary excretion and calcium/creatinine urinary
      rate). Quality of life was studied using the short form 36 questionnaire (SF-36).
      Blood tests included total testosterone, sex hormone binding-globulin, calculated
      free testosterone (cFT), dehydroepiandrosterone sulphate (DHEA-S),
      androstenedione, 17-beta-estradiol and gonadotrophins. RESULTS: cFT was
      associated with increased muscle and to decreased in fat content, even after
      adjusting for age (p<0.05). Bone density was only related to estradiol and its
      bioavailable fraction (p<0.05). DHEA-S and cFT were related (p<0.05) to some SF
      36 subscales. CONCLUSIONS: cFT level is most associated with body changes that
      accompany aging. Androgen levels are not related to bone density. Decline in cFT
      and DHEA-s levels might be related to decreased quality of life.

PMID- 21742418
TI  - [Comparison of the operation time and complications between conventional and
      robotic-assisted laparoscopic pyeloplasty].
AB  - OBJECTIVE: To compare the different times into which the convention and robotic
      assisted laparoscopic pyeloplasty can be divided. To compare the rate of
      complications between both procedures. MATERIAL AND METHODS: A retrospective
      study was performed of the patients diagnosed of pyeloureteral junction stenosis
      and treated with convention and robotic laparoscopic pyeloplasty with more than
      one year of follow-up. All of the interventions were recorded and visualized. The
      different times in which the pyeloplasty can be divided were measured. All of the
      peri- and post-operative complications that occurred by the patients were
      collected. The non-parametric tests of Kolmogorov-Smirnov and Mann-Whitney U-Test
      for independent samples were applied using a significance level of 0.05. RESULTS:
      A total of 50 patients were validated. Thirty three were treated with convention
      laparoscopy and 17 with robotic laparoscopy. The suture time, total intervention
      time and time of hospital stay were lower with a statistically significant
      difference in the robotic-assisted pyeloplasty. The robotic pyeloplasty had a
      lower percentage of complications (76.5% vs 48.5%). The most frequent
      complications were urinary infections, in relationship to the double J. Two
      restenoses occurred in the conventional laparoscopy and one in the robotic
      assisted. Success rate was 93.9% for the conventional laparoscopy and 94.1% for
      the robotic-assisted one. CONCLUSIONS: Although the success rate is similar in
      both procedures, the robotic pyeloplasty is a very fast procedure and has lower
      rates of complications than the conventional laparoscopy.

PMID- 21742419
TI  - 18F-FDG-PET/CT in the surveillance of patients with lymphoma: detection of
      asymptomatic recurrences.
AB  - AIM: To assess the diagnostic accuracy of (18)F-FDG-PET/CT in detecting
      asymptomatic recurrences in patients with lymphoma. To define uptake patterns of
      recurrence indicative of recurrence. MATERIAL AND METHODS: Those patients with
      lymphoma who fulfilled the following inclusion criteria of clinical complete
      remission and negative PET/CT study were included retrospectively and
      longitudinally. Conventional surveillance of these patients was performed only by
      (18)F-FDG PET/CT following a standardized procedure. Pathologic locations (supra-
      and infradiaphragmatic) and their character (single or multiple) were analyzed in
      order to determine reliable metabolic patterns of recurrence. The final diagnosis
      was established by histopathological analysis or clinical follow-up greater than
      8 months. RESULTS: A total of 199 explorations belonging to 106 patients with
      lymphoma were included. Of these patients, 59 had Hodgkin's lymphoma and 47 non
      Hodgkin's lymphoma. There was suspicion of relapse from the metabolic point of
      view in 27 of the PET/CT scans. Of these, 14 (10 patients) were false positive
      (FP), and 13 (8 patients) true positive. The remaining studies were true
      negative, no false negatives being detected. The pattern most frequently related
      to recurrence was infradiaphragmatic lymph node involvement while most of the FP
      had isolated supradiaphragmatic involvement. Sensitivity, specificity, PPV, NPV
      and diagnostic accuracy of PET/CT parameters for the study were 100%, 92%, 48%,
      100% and 93%, respectively. CONCLUSION: (18)F-FDG-PET/CT is a sensitive technique
      in the detection of asymptomatic recurrences in patients with lymphoma during
      their follow-up. Multiple character and infradiaphragmatic locations were the
      patterns that best correlated to the diagnosis of recurrence.

PMID- 21742420
TI  - [Chronic hepatitis B infection in Sub-Saharan African immigrants].

PMID- 21742421
TI  - Metabolism evaluation of the anticancer candidate AC04 by biomimetic oxidative
      model and rat liver microsomes.
AB  - Jacobsen reagents, in the presence of monooxygen donors, appear as an alternative
      to produce metabolites from biological active compounds. This reaction may mimic
      the oxidation and oxygenation reactions of cytochrome P450 (CYP450) enzymes upon
      various drugs and biologically active compounds. Acridines represent a well-known
      group of polyaromatic compounds capable of acting as DNA intercalating agents.
      Viewing to search for new anticancer agents, one promising new acridine, the 5
      acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione (AC04) (2), has
      been studied by our group and the in vitro metabolism was investigated in this
      work, aiming to advance in the pre-clinical pharmacokinetic investigation. A
      systematic investigation of the gas-phase reaction, supported by computational
      chemistry, of the AC04 (2) was studied to help the structure elucidation of
      possible in vivo metabolites. To confirm the methodology, the oxidized product
      was obtained in large scale for NMR analysis and the data confirmed the
      structure. In addition, AC04 (2) was submitted to an in vitro metabolism assay
      employing rat liver microsomes and also, a pilot study was conducted in rats
      after AC04 intravenous (i.v.) dosing of 1.5 mg/kg. A single oxidized product was
      obtained from microsomal metabolism and detected in rat plasma by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis corresponding to the
      same product formed by Jacobsen-catalyzed reaction. These results indicate that
      Jacobsen oxidation reactions, combined with in vitro metabolism assays employing
      isolated microsomes, might replace some in vivo metabolism studies, thus reducing
      the use of animals in new chemical entities pre-clinical investigation.

PMID- 21742422
TI  - Influence of close resection margins on local recurrence and disease-specific
      survival in oral and oropharyngeal carcinoma.
AB  - There is a lack of consistency among published reports in the definition of what
      constitutes close resection margins (1-5mm) in the surgical treatment of oral and
      oropharyngeal squamous cell carcinoma (SCC). Our aim was to define what would
      constitute close resection margins in predicting local recurrence and disease
      specific survival. The study comprised 192 previously untreated patients with
      oral and oropharyngeal SCC who were recruited at the Southern General Hospital,
      Glasgow, from 2001 to 2007 with a minimum follow-up of 2 years. Resection was the
      primary treatment and the surgical margins were recorded for all patients.
      Statistical analyses were aided by the Statistical Package for the Social
      Sciences, version 15.0, and MedCalc software. The status of the surgical margins
      was evaluated using a receiver operating characteristic (ROC) curve to define the
      cut-off point. Cox's proportional hazard model was used to establish predictive
      factors for local recurrence and disease-specific survival. Of 192 patients, 23
      (12%) had involved margins (<1.0mm), 107 (56%) had close margins (1.0-2.0mm
      (16.1%); 2.1-3.0mm (12%); 3.1-4.0mm (10.4%); 4.1-5.0mm (17.2%), and 62 (32.3%)
      had clear margins (>5mm). No predictive cut-off point was found that related
      close surgical margins to local recurrence. However, there was a significant
      adverse association between surgical margins <=1.6mm and disease-specific
      survival. In recommending postoperative adjuvant treatment for oral and
      oropharyngeal SCC, we suggest that surgical margins within 2mm should be
      considered as the cut-off. However, other clinical and pathological prognostic
      factors should also be taken into consideration when recommending further
      treatment.

PMID- 21742423
TI  - JAK inhibitors in myeloproliferative neoplasms: rationale, current data and
      perspective.
AB  - JAK-STAT is an appealing but also problematic drug target in BCR-ABL1-negative
      myeloproliferative neoplasms (MPN) - it is appealing because the majority of
      patients with MPN harbor gain-of-function JAK2 or MPL mutations - it is
      problematic because currently available JAK inhibitors do not distinguish between
      oncogenic and physiologic JAK-STAT activation. Furthermore, JAK-STAT-relevant
      mutations in MPN do not always constitute the predominant or ancestral mutant
      clone. Such complexities undermine the value of JAK-STAT as a robust drug target
      in MPN and partly explain the hitherto lack of histologic or molecular remissions
      associated with currently available JAK inhibitors. Most of these drugs were,
      however, effective in alleviating constitutional symptoms and reducing spleen
      size; the mechanism of action in this instance includes drug-induced down
      regulation of inflammatory cytokine activity. In addition, non-specific
      myelosuppression contributes to both their salutary and detrimental effects on
      peripheral blood count. Non-hematologic side effects include gastrointestinal
      disturbances, asymptomatic elevation of liver and pancreatic enzymes, peripheral
      neuropathy and hyperacute relapse of symptoms during treatment interruption. It
      is our impression that many more JAK inhibitors need to be evaluated in order to
      identify the best-in-class in terms of efficacy, toxicity and suitability for
      future combination treatment programs.

PMID- 21742424
TI  - Distributions of polyhalogenated compounds in Hudson River (New York, USA) fish
      in relation to human uses along the river.
AB  - PCBs (as Aroclor concentrations) have been extensively examined in fish along the
      Hudson River, but other xenobiotic chemicals in fish have had limited assessment.
      This study determined concentrations and congener distributions of polybrominated
      diphenyl ethers (PBDEs), polybrominated and polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PBDD/Fs and PCDD/Fs), and polychlorinated biphenyls (PCBs) in
      smallmouth bass and striped bass taken from a 385 km reach of the Hudson River.
      Concentrations of PBDEs and PCBs in smallmouth bass, and PCBs in striped bass,
      were positively related to human uses of the compounds in the basin. Generally
      low levels of PCDD/Fs were found. One striped bass, however, contained elevated
      2,3,7,8-TCDD, indicating exposure to a known source in the adjacent Newark Bay
      Passaic River basin. PBDDs were generally below detection. PBDFs were present in
      four of 18 smallmouth bass, but were not detected in striped bass. Dioxin-like
      PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples.

PMID- 21742425
TI  - Does maternal autonomy influence feeding practices and infant growth in rural
      India?
AB  - The high prevalence of child under-nutrition remains a profound challenge in the
      developing world. Maternal autonomy was examined as a determinant of breast
      feeding and infant growth in children 3-5 months of age. Cross-sectional baseline
      data on 600 mother-infant pairs were collected in 60 villages in rural Andhra
      Pradesh, India. The mothers were enrolled in a longitudinal randomized behavioral
      intervention trial. In addition to anthropometric and demographic measures, an
      autonomy questionnaire was administered to measure different dimensions of
      autonomy (e.g. decision-making, freedom of movement, financial autonomy, and
      acceptance of domestic violence). We conducted confirmatory factor analysis on
      maternal autonomy items and regression analyses on infant breast feeding and
      growth after adjusting for socioeconomic and demographic variables, and
      accounting for infant birth weight, infant morbidity, and maternal nutritional
      status. Results indicated that mothers with higher financial autonomy were more
      likely to breastfeed 3-5 month old infants. Mothers with higher participation in
      decision-making in households had infants that were less underweight and less
      wasted. These results suggest that improving maternal financial and decision
      making autonomy could have a positive impact on infant feeding and growth
      outcomes.

PMID- 21742426
TI  - Mental health interventions for children in adversity: pilot-testing a research
      strategy for treatment selection in low-income settings.
AB  - This study aimed to develop a research strategy to make informed decisions for
      intervention selection, especially for low- and middle-income countries, as a
      response to the urgent need to scale-up mental health care for children globally.
      With this study we address the critical lack of translation of research findings
      into policy and practice. The research strategy was piloted for development of a
      family-based intervention in violence-affected areas in Burundi. The research
      comprised four phases; (a) a qualitative phase to assess needs and determine
      tentative intervention objectives; (b) a global expert panel to identify and
      prioritize intervention modalities for low-resource settings; (c) systematic
      literature review and distillation of practice elements from evidence-based
      treatments; and (d) stakeholder meetings to explore social-cultural feasibility
      and acceptability of the developed intervention. The study was conducted between
      January and November 2010. The research strategy resulted in the development of a
      stepped family-based care intervention, which combines community mobilization,
      parent-management training and cognitive behavior therapy elements. This pilot
      tested research strategy, encompassing global and local knowledge on needs,
      feasibility and effectiveness, has the potential to be useful for developing
      mental health and psychosocial interventions in other settings.

PMID- 21742427
TI  - New resuscitation guidelines may result in an increased incidence of severe chest
      wall injury, and lead to prolonged length of stay in the Intensive Care Unit.

PMID- 21742428
TI  - The introduction of intra-operative cell salvage in obstetric clinical practice:
      a review of the available evidence.
AB  - Intra-operative blood salvage is common practice in many surgical specialties but
      its safety is questioned with concerns about the risks of contamination of
      recovered blood with amniotic fluid and of maternal-foetal alloimmunization.
      However, the role of cell salvage as a blood-saving measure in this clinical
      setting is progressively acquiring relevance thanks to the growing body of
      evidence regarding its quality and safety. Modern cell savers remove most
      particulate contaminants and leukodepletion filtering of salvaged blood prior to
      transfusion adds further safety to this technique. Amniotic fluid embolism is no
      longer regarded as an embolic disease and the contamination of the salvaged blood
      by foetal Rh-mismatched red blood cells can be dealt with using anti-D
      immunoglobulin; ABO incompatibility tends to be a minor problem since ABO
      antigens are not fully developed at birth. Maternal alloimmunization can be
      caused also by other foetal red cell antigens, but it should also be noted that
      the risk of alloimmunization of the mother from allogeneic transfusion may be
      even greater. Therefore the use of cell savers in obstetric clinical practice
      should be considered in patients at high risk for haemorrhage or in cases where
      allogeneic blood transfusion is difficult or impossible.

PMID- 21742429
TI  - Interactions of replication versus repair DNA substrates with the Pol I DNA
      polymerases from Escherichia coli and Thermus aquaticus.
AB  - Different DNA polymerases partition differently between replication and repair
      pathways. In this study we examine if two Pol I family polymerases from
      evolutionarily distant organisms also differ in their preferences for replication
      versus repair substrates. The DNA binding preferences of Klenow and Klentaq DNA
      polymerases, from Escherichia coli and Thermus aquaticus respectively, have been
      studied using a fluorescence competition binding assay. Klenow polymerase binds
      primed-template DNA (the replication substrate) with up to 50* higher affinity
      than it binds to nicked DNA, DNA with a 2 base single-stranded gap, blunt-ended
      DNA, or to a DNA end with a 3' overhang. In contrast, Klentaq binds all of these
      DNAs almost identically, indicating that Klenow has a stronger ability to
      discriminate between replication and repair substrates than Klentaq. In contrast,
      both polymerases bind mismatched primed-template and blunt-ended DNA tighter than
      they bind matched primed-template DNA, suggesting that these two proteins may
      share a similar mechanism to identify mismatched DNA, despite the fact that
      Klentaq has no proofreading ability. In addition, the presence or absence of 5'-
      or 3'-phosphates has slightly different effects on DNA binding by the two
      polymerases, but again reinforce Klenow's more effective substrate discrimination
      capability.

PMID- 21742430
TI  - Reducing surface water pollution through the assessment of the cost-effectiveness
      of BMPs at different spatial scales.
AB  - Two kinds of agricultural Best Management Practices (BMPs) were examined with
      respect to cost-effectiveness (CE) in reducing sediment, nitrates-nitrogen (NO(3)
      N) and total phosphorus (TP) losses to surface waters of the Arachtos catchment
      in Western Greece. The establishment of filter strips at the edge of fields and a
      non-structural measure, namely fertilization reduction in alfalfa, combined with
      contour farming and zero-tillage in corn and reduction of animal numbers in
      pastureland, were evaluated. The Soil and Water Assessment Tool (SWAT) model was
      used as the non-point-source (NPS) estimator, while a simple economic component
      was developed estimating BMP implementation cost as the mean annual expenses
      needed to undertake and operate the practice for a 5-year period. After each BMP
      implementation, the ratio of their CE in reducing pollution was calculated for
      each Hydrologic Response Unit (HRU) separately, for each agricultural land use
      type entirely and for the whole catchment. The results at the HRU scale are
      presented comprehensively on a map, demonstrating the spatial differentiation of
      CE ratios across the catchment that enhances the identification of locations
      where each BMP is most advisable for implementation. Based on the analysis, a
      catchment management solution of affordable total cost would include the
      expensive measure of filter strips in corn and only in a small number of
      pastureland fields, in combination with the profitable measure of reducing
      fertilization to alfalfa fields. When examined for its impact on river loads at
      the outlet, the latter measure led to a 20 tn or 8% annual decrease of TP from
      the baseline with savings of 15?/kg of pollutant reduction. Filter strips in corn
      fields reduced annual sediments by 66 Ktn or 5%, NO(3)-N by 71 tn or 9.5% and TP
      by 27 tn or 10%, with an additional cost of 3.1 ?/tn, 3.3 ?/kg and 8.1 ?/kg of
      each pollutant respectively. The study concludes that considerable reductions of
      several pollutant types at the same time can be achieved, even at low total cost,
      by combining targeted BMP implementation strategies only in small parts of the
      catchment, also enabling policy makers to take local socio-economic constraints
      into consideration. The methodology and the results presented aim to facilitate
      decision making for a cost-effective management of diffuse pollution by enabling
      modelers and researchers to make rapid and reliable BMP cost estimations and thus
      being able to calculate their CE at the local level in order to identify the most
      suitable areas for their implementation.

PMID- 21742431
TI  - Autonomous real-time adaptive management of soil salinity using a receding
      horizon control algorithm: a pilot-scale demonstration.
AB  - Soil salinization is a potentially negative side effect of irrigation with
      reclaimed water. While optimization schemes have been applied to soil salinity
      control, these have typically failed to take advantage of real-time sensor
      feedback. This study incorporates current soil observation technologies into the
      optimal feedback-control scheme known as Receding Horizon Control (RHC) to enable
      successful autonomous control of soil salinization. RHC uses real-time sensor
      measurements, physically-based state prediction models, and optimization
      algorithms to drive field conditions to a desired environmental state by
      manipulating application rate or irrigation duration/frequency. A simulation
      model including the Richards equation coupled to energy and solute transport
      equations is employed as a state estimator. Vertical multi-sensor arrays
      installed in the soil provide initial conditions and continuous feedback to the
      control scheme. An optimization algorithm determines the optimal irrigation rate
      or frequency subject to imposed constraints protective of soil salinization. A
      small-scale field test demonstrates that the RHC scheme is capable of
      autonomously maintaining specified salt levels at a prescribed soil depth. This
      finding suggests that, given an adequately structured and trained simulation
      model, sensor networks, and optimization algorithms can be integrated using RHC
      to autonomously achieve water reuse and agricultural objectives while managing
      soil salinization.

PMID- 21742432
TI  - Establishment of pemetrexed-resistant non-small cell lung cancer cell lines.
AB  - Pemetrexed (PEM), a multitargeted antifolate with manageable toxicity, is active
      against non-squamous non-small cell lung cancer; however, most patients
      eventually acquire resistance to PEM. To elucidate the resistant mechanism, we
      established PEM-resistant lung adenocarcinoma cell lines. Two parental cell
      lines, PC-9 and A549, were treated with step-wise increasing concentrations of
      PEM. Growth inhibition was determined by the 3-[4,5-dimethyl-thizol-2-yl]-2,5
      diphenyltetrazolium bromide assay. Expression of the genes encoding thymidylate
      synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide
      formyltransferase (GARFT) was analyzed by quantitative real-time reverse
      transcriptase polymerase chain reaction. The four PC-9 sublines were more
      resistant than the PC-9 cell line to PEM (2.2-, 2.9-, 8.4-, and 14.3-fold,
      respectively). The four A549 sublines also showed more resistance to PEM (7.8-,
      9.6-, 42.3-, and 42.4-fold, respectively) than the parent cell line. All
      resistant sublines showed cross-resistance to cisplatin, but not to docetaxel,
      vinorelbine, 5-fluorouracil, or the active metabolite of irinotecan, SN-38. All
      PEM-resistant sublines expressed more TS than the parental cells, by polymerase
      chain reaction and Western blotting. DHFR was significantly increased in the four
      PEM-resistant A549 sublines. GARFT did not correlate with resistance to PEM. In
      summary, PEM-resistant cells remained sensitive to docetaxel, vinorelbine, 5
      fluorouracil, and irinotecan. TS expression appeared to be associated with
      resistance to PEM.

PMID- 21742433
TI  - Functionalized cotton via surface-initiated atom transfer radical polymerization
      for enhanced sorption of Cu(II) and Pb(II).
AB  - The surface-initiated atom transfer radical polymerization (ATRP) was used to
      successfully prepare the aminated cotton and polyacrylic acid sodium (P(AA-Na))
      grafted cotton for the efficient removal of Cu(II) and Pb(II) from aqueous
      solution in this study. The modified cotton surfaces were characterized by
      scanning electron microscopy (SEM), Fourier transform infrared (FTIR) and X-ray
      photoelectron spectroscopy (XPS). The grafted long polymers with high density of
      amine and carboxyl groups on the cotton surfaces were responsible for the
      enhanced adsorption of heavy metals. The sorption behaviors including sorption
      kinetics, isotherms and pH effect were investigated. The sorption equilibrium of
      Cu(II) and Pb(II) was achieved within 1h on the P(AA-Na)-grafted cotton, much
      faster than 8h on the aminated cotton. According to the Langmuir fitting, the
      maximum sorption capacities of Cu(II) and Pb(II) on the P(AA-Na)-grafted cotton
      were 2.45 and 2.44 mmol/g, respectively, higher than many adsorbents reported in
      the literature. The P(AA-Na)-grafted cotton had better adsorption behaviors for
      Cu(II) and Pb(II) than the aminated cotton.

PMID- 21742434
TI  - Study of PAH dissipation and phytoremediation in soils: comparing freshly spiked
      with weathered soil from a former coking works.
AB  - A comparison was made between the dissipation of polycyclic aromatic hydrocarbons
      (PAHs) in soil freshly spiked with pure PAHs, soil spiked with a coal tar mixture
      and a contaminated soil from a former coking works where the PAHs had been
      present for more than a century. The potential of five selected plant species for
      phytoremediation was investigated. The levels of all 7 PAHs in chemically amended
      soil, both planted and unplanted, fell significantly (>80% reduction) over the 12
      weeks of the growing trial. In the coal tar treated soils all PAHs were
      significantly reduced. In both the planted and unplanted soils the 2-3 ringed
      compounds demonstrated much greater loss (>77%) than the 4-6 ringed (16-39%). The
      3-4 ringed compounds demonstrated strong evidence of phytoremediation but not the
      5-6 ringed. The coking soil showed limited reduction (7-24%) of all 12 PAHs
      present. There was little difference in dissipation between the PAHs and little
      evidence of a phytoremediation effect in coking soil. The results demonstrated
      that the form in which PAHs were added to soil influenced their susceptibility to
      dissipation. Therefore, predictions of PAH dissipation from laboratory amended
      soil do not reflect the true situation in the field.

PMID- 21742435
TI  - Anatase-brookite mixed phase nano TiO2 catalyzed homolytic decomposition of
      ammonium nitrate.
AB  - Compared to the conventional ammonium perchlorate based solid rocket propellants,
      burning of ammonium nitrate (AN) based propellants produce environmentally
      innocuous combustion gases. Application of AN as propellant oxidizer is
      restricted due to low reactivity and low energetics besides its near room
      temperature polymorphic phase transition. In the present study, anatase-brookite
      mixed phase TiO(2) nanoparticles (~ 10 nm) are synthesized and used as catalyst
      to enhance the reactivity of the environmental friendly propellant oxidizer
      ammonium nitrate. The activation energy required for the decomposition reactions,
      computed by differential and non-linear integral isoconversional methods are used
      to establish the catalytic activity. Presumably, the removal of NH(3) and H(2)O,
      known inhibitors of ammonium nitrate decomposition reaction, due to the surface
      reactions on active surface of TiO(2) changes the decomposition pathway and
      thereby the reactivity.

PMID- 21742436
TI  - Electrochemical degradation of a real textile effluent using boron-doped diamond
      or beta-PbO2 as anode.
AB  - Constant current electrolyses are carried out in a filter-press reactor using a
      boron-doped diamond (Nb/BDD) or a Ti-Pt/beta-PbO(2) anode, varying current
      density (j) and temperature. The degradation of the real textile effluent is
      followed by its decolorization and chemical oxygen demand (COD) abatement. The
      effect of adding NaCl (1.5 g L(-1)) on the degradation of the effluent is also
      investigated. The Nb/BDD anode yields much higher decolorization (attaining the
      DFZ limit) and COD-abatement rates than the Ti-Pt/beta-PbO(2) anode, at any
      experimental condition. The best conditions are j = 5 mA cm(-2) and 55  degrees
      C, for the system's optimized hydrodynamic conditions. The addition of chloride
      ions significantly increases the decolorization rate; thus a decrease of more
      than 90% of the effluent relative absorbance is attained using an applied
      electric charge per unit volume of the electrolyzed effluent (Q(ap)) of only
      about 2 kA h m(-3). Practically total abatement of the effluent COD is attained
      with the Nb/BDD anode using a Q(ap) value of only 7 kA h m(-3), with an energy
      consumption of about 30 kW h m(-3). This result allows to conclude that the
      Nb/BDD electrode might be an excellent option for the remediation of textile
      effluents.

PMID- 21742437
TI  - Modulation of immune response to Toxoplasma gondii in sheep by immunization with
      a DNA vaccine encoding ROP1 antigen as a fusion protein with ovine CD154.
AB  - CD154 is a cell surface molecule expressed by activated T cells. CD40 and CD154
      interaction is critically important in regulating humoral and cell-mediated
      immune responses. In this study we have investigated whether a DNA vaccine
      encoding rhoptry protein 1 (ROP1) of Toxoplasma gondii, and encoding ovine CD154
      induces an enhanced ROP1-specific immune response in sheep. Two groups of twelve
      animals received two intramuscular injections, of a DNA plasmid encoding T.
      gondii ROP1 antigen (group 1) or an ROP1 antigen fused to ovine CD154 (group 2).
      There were two control groups of sheep. One was injected with an empty vector
      (group 3) and the other received no injections at all (group 4). The injection of
      the plasmid containing ROP1 (group 1) at weeks 0 and 4 induced a significant IgG2
      response at week 2 which was amplified at week 4 after the booster injection and
      persisted to week 8 compared to the control animals in groups 3 and 4. For IgG1,
      significant differences from the control animals were only observed from week 5
      onwards. The fusion of CD154 and ROP1 elicited significant IgG1 and IgG2
      responses from week 1 which were amplified from weeks 5 to 8 compared to the
      control animals in groups 3 and 4. The IgG1 response was significantly higher in
      group 2 animals receiving pROP1-CD154 compared to group 1 receiving pROP1 only.
      There was no significant difference in IgG2 responses between groups 1 and 2.
      Significant differences in IFN-gamma levels were only observed in treatment group
      1 at week 2 and treatment group 2 at weeks 1 and 2 compared to the control
      animals. The results demonstrated that an intramuscular injection of pROP1-CD154
      gene to sheep significantly enhanced their immune response and induced a mixed
      Th1/Th2 response while the intramuscular injection of pROP1 only induced a Th1
      specific immune response.

PMID- 21742438
TI  - Oral vinorelbine in metastatic breast cancer: a review of current clinical trial
      results.
AB  - BACKGROUND: Oral chemotherapy is one of the options for the treatment of
      endocrine non-responsive metastatic breast cancer. PATIENTS AND METHODS: A search
      of the online PubMed database was undertaken to identify clinical trials
      evaluating oral vinorelbine in metastatic breast cancer. All the clinically
      relevant data have been analysed in this article. RESULTS: A total of 31 studies
      including more than 1000 patients have been included into this analysis. Oral
      vinorelbine either as a single-agent or in combination has shown consistent
      efficacy results (response rates between 27% and 85% in first-line). The all-oral
      combination of oral vinorelbine and capecitabine has shown comparable efficacy to
      a taxane-based combination in a randomised phase II study. Importantly, activity
      has also been observed in the subset of patients previously treated with
      anthracyclines and taxanes. For HER2-positive patients, oral vinorelbine in
      combination with trastuzumab is among the most active options. Oral vinorelbine
      presents a manageable tolerance profile. Neutropenia is the most common adverse
      event and alopecia is not frequently observed. Anti-emetic prophylaxis is
      recommended. CONCLUSION: Taken together, these data indicate that oral
      vinorelbine is a highly effective and well tolerated agent which can be used in
      first-line and subsequent metastatic breast cancer settings. Moreover, this
      compound may offer the specific advantages of oral chemotherapy, as fewer and
      shorter hospital visits, delayed use of central venous access devices and
      maintained social activities.

PMID- 21742439
TI  - The role of PET imaging in overcoming radiobiological challenges in the treatment
      of advanced head and neck cancer.
AB  - PURPOSE: Despite the large variety of treatment methods available for the
      management of advanced head and neck carcinomas, these tumours remain highly
      challenging due to their aggressiveness and complex anatomical location. Among
      the treatment challenges associated with head and neck cancers, hypoxia and
      tumour repopulation during treatment are, most likely, the main reason for
      locoregional treatment failure. Whilst the number of techniques and predictive
      assays designed to assess the oxygenation status or the proliferative ability of
      tumours is rather large, they all come with drawbacks which limit their
      implementation as routine clinical procedures. Latest developments in the field
      of nuclear medicine have opened the road to new possibilities in functional
      imaging, thus overcoming some of the confines imposed by the more conventional
      techniques. MATERIALS AND METHODS: The current paper presents the role of PET
      imaging as a quantitative evaluation tool for hypoxia status and proliferative
      ability of advanced head and neck tumours. Traditional as well as novel
      radioisotopes with high affinity towards hypoxia and proliferative tumour
      activity are presented and their pre-clinical/clinical results analysed. RESULTS:
      While the number of clinical studies which aimed to validate novel radiotracers
      for head and neck cancer is limited, a number of results show promising
      correlation between uptake/marker activity and treatment outcome. CONCLUSION:
      There is need for further studies and well designed clinical trials to obtain
      more conclusive results.

PMID- 21742440
TI  - To live alone and to be depressed, an alarming combination for the renin
      angiotensin-aldosterone-system (RAAS).
AB  - INTRODUCTION: The renin-angiotensin-aldosterone-system (RAAS) is one of the most
      important systems involved in the pathogenesis of cardiovascular diseases. Its
      role in stress response has been generally neglected, although the progression of
      cardiovascular disease is considerably increased in the presence of stress and
      especially in the presence of depression risk. With the present analysis we aimed
      to evaluate whether the activity of the RAAS correlates with depressive
      symptomatology and with chronic stress. Moreover, we aimed to analyse whether
      stress response is altered in the presence of depressed symptomatology. We chose
      "living alone" to be our paradigm of chronic stress. METHODS AND RESULTS:
      Aldosterone and renin levels were assessed in 1743 (829 men, 914 women) from the
      population-based KORA study (Cooperative Health Research in the Region of
      Augsburg). The relationship between aldosterone, renin levels and the different
      combinations of living alone and depressive symptomatology was examined in three
      different multiple linear regression models adjusted for age, sex, creatinine
      levels, potassium levels, body mass index (BMI) and bio-behavioural factors.
      Neither "living alone" nor depressive symptomatology alone were associated with
      an activation of the RAAS, but the combination of living alone and depressive
      symptomatology yielded a highly significant increase in the aldosterone (p<0.01)
      and renin level (p=0.03). CONCLUSION: Our findings show that depressive
      symptomatology is associated with a hyper-responsiveness to chronic stress. Under
      the condition of chronic stress depressed individuals have an activated RAAS.
      Activation of the RAAS might explain the known increased risk of negative
      cardiovascular disease outcomes in this group.

PMID- 21742441
TI  - Sex-specific associations between sleep problems and hypothalamic-pituitary
      adrenocortical axis activity in children.
AB  - STUDY OBJECTIVES: Sleep problems are associated with reduced physical and mental
      health. Altered function of the hypothalamic-pituitary-adrenocortical axis (HPAA)
      may be one underlying mechanism. We studied the associations between sleep
      problems and HPAA activity in children. DESIGN: A cross-sectional epidemiological
      cohort study. SETTING: Salivary cortisol was sampled throughout one day at home
      and during the Trier Social Stress Test for Children (TSST-C) in clinic. Sleep
      disorders were measured with a parent-rated Sleep Disturbance Scale for Children,
      and sleep duration measured by actigraphy for one week. PARTICIPANTS: 284 (51%
      girls) 8-year-old children. RESULTS: Boys with sleep problems (>= 85 th
      percentile in any of the sleep-wake transition, arousal, excessive daytime
      somnolence or sleep hyperhydrosis subscales) had lower diurnal salivary cortisol
      levels and salivary cortisol responses to TSST-C stress in comparison to boys
      without sleep problems. Girls with sleep problems (>= 85 th percentile in
      disorders of initiating and maintaining sleep) displayed a higher overall level
      of salivary cortisol during the TSST-C. Salivary cortisol responses to stress
      were lower in boys and higher in girls with more than one sleep problem.
      CONCLUSIONS: Sleep problems in children are associated with altered HPAA
      function, after controlling for actual sleep quantity measured by actigraphy.
      Boys with sleep problems had lower HPAA activity and girls with sleep problems
      had higher HPAA activity, compared to children without sleep problems.

PMID- 21742442
TI  - Depersonalization disorder may be related to glutamate receptor activation
      imbalance.
AB  - Low-dose ketamine administration mimics, both clinically and on gross
      neuroimaging, depersonalization disorder. The perceptual effects of ketamine may
      be due to secondary stimulation of glutamate release and lamotrigine, possibly by
      inhibited glutamate release, may reduce some of ketamine's so-called dissociative
      effects. However, lamotrigine does not seem to be useful in the treatment of
      depersonalization disorder. Glutamate release in prefrontal cortex is increased
      by subanaesthetic doses of ketamine, resulting in increased inhibition, possibly
      via intercalated GABAerg cells, of projections from amygdala, affecting
      structures critically involved in depersonalization. I speculate that, in
      depersonalization disorder, the increased glutamate activity in prefrontal cortex
      is due to intrinsic imbalance, resulting in long-term potentiation, at the
      postsynaptic glutamate receptors on the GABAerg interneurons while the same
      receptor abnormality at the synapses on the intercalated GABAerg cells of the
      amygdala result in long-term depression in the case of either normal or high
      glutamate release.

PMID- 21742443
TI  - Influence of chestnut tannins on welfare, carcass characteristics, meat quality,
      and lipid oxidation in rabbits under high ambient temperature.
AB  - A study was conducted to evaluate the influence of chestnut tannins (CT) on
      welfare, carcass characteristics, meat quality, and lipid oxidation in rabbits
      under high ambient temperature. Rabbits in one group were raised at 20 degrees C
      and fed with basal diet (N) and other three groups (33 degrees C) were fed basal
      diet with 0 (C), 5 (CT5), and 10 g (CT10) of CT/kg of diet. Compared with the C
      group, rabbits in CT10 had higher pH(24) and lower cooking loss and
      thiobarbituric acid reacting substance values at 0, 30, and 60 min of forced
      oxidation. Rabbits in C group had higher cortisol levels, creatine kinase
      activities, white blood cell counts, neutrophil percentage, neutrophil:lymphocyte
      ratio and lower T(3), T(4) levels, lymphocyte percentage than N and CT10 groups.
      Supplementation of CT seemed to have a positive effect on growth performance,
      welfare, and meat quality of rabbits under high ambient temperature.

PMID- 21742444
TI  - [Influence of HIV-1 and placental malaria co-infection on newborn biometry and
      Apgar scores in Kinshasa, Democratic Republic of Congo].
AB  - OBJECTIVE: The aim of this study was to assess the impact of HIV-1 and placental
      malaria co-infection on newborn biometry and Apgar scores. METHODS: 146 HIV-1
      infected and 149 HIV-1 uninfected consent mothers and their newborns were
      recruited. Placental biopsies examination confirmed the presence or absence of
      placental malaria. Birth weight (BW), placental weight, cranial circumference,
      brachial perimeter, height, Body Mass Index (BMI) and Apgar scores at 1', 5', 10'
      were taken. The Chi(2) test and t-Student test were used for data statistical
      analysis. RESULTS: The global placental malarial infection prevalence was 72% but
      was 91% in HIV-1 infected vs. 53.7% in HIV-1 uninfected mothers (p<0.0001). The
      mean BW of HIV-1 co-infected mother's newborns was slightly inferior to that of
      HIV-1 uninfected mother's babies (3,033+/-524g vs. 3,236+/-565g) but this
      difference was not statistically significant (p>0.05). No other significant
      biometric differences were noted (p>0.05). But, the co-infection influenced
      negatively Apgar scores at 5' (p<0.05). CONCLUSION: HIV-1 co-infected mothers
      were more frequently exposed to placental malaria infection. The co-infection
      reduced the Apgar scores taken at the fifth minute.

PMID- 21742445
TI  - Drug use and HIV risk outcomes in opioid-injecting men in the Republic of
      Georgia: behavioral treatment + naltrexone compared to usual care.
AB  - BACKGROUND: To test the initial feasibility of a novel 22-week comprehensive
      intervention pairing behavioral treatment with naltrexone that aimed at engaging,
      retaining, and treating opioid-injecting men in the Republic of Georgia. METHODS:
      Forty opioid-injecting male and their drug-free female partners participated in a
      two-group randomized clinical trial at the field site of the Union Alternative
      Georgia, in Tbilisi, Republic of Georgia. The comprehensive intervention that
      paired behavioral treatment with naltrexone for the male participants (n=20)
      included counseling sessions using Motivational Interviewing for both the male
      participant and the couple, monetary incentives for drug abstinence, and research
      supported detoxification followed by naltrexone treatment. Male participants in
      the usual care condition (n=20) had the opportunity to attend once-a-week
      individualized education sessions and upon request receive referrals to
      detoxification programs and aftercare that could or could not have included
      naltrexone. Outcome measures included entry into inpatient detoxification and
      naltrexone treatment, urine drug screening, reduction in illicit substance use,
      use of benzodiazepines, injection of buprenorphine, and needle and syringe
      sharing. RESULTS: The comprehensive intervention condition showed significantly
      more weekly urine samples negative for illicit opioids during weeks 1-22 (7.0 vs.
      1.4; p<.001) and reported significant declines in use of benzodiazepines and
      injection of buprenorphine (both ps<.004). CONCLUSIONS: The first behavioral
      treatment randomized clinical trial in the Republic of Georgia found that the use
      of tailored behavioral therapy paired with naltrexone is both feasible and
      efficacious for treating drug use and reducing HIV drug-risk behavior in Georgian
      men.

PMID- 21742446
TI  - Defective bacterial clearance is responsible for the enhanced lung pathology
      characteristic of Mannheimia haemolytica pneumonia in bighorn sheep.
AB  - The molecular and cellular basis for the enhanced lung pathology and mortality
      caused by Mannheimia haemolytica in bighorn sheep (BHS, Ovis canadenesis), in
      comparison to domestic sheep (DS, Ovis aries), is not clear. Polymorphonuclear
      leukocytes (PMNs) of BHS are four- to eight-fold more susceptible to M.
      haemolytica leukotoxin-induced cytolysis, which is likely to reduce the number of
      functional phagocytes in the lung. We hypothesized that enhanced lung pathology
      is due to defective clearance of M. haemolytica from the lungs of BHS. To test
      this hypothesis, M. haemolytica (1 * 10(7) colony forming units [cfu]) were
      inoculated intra-tracheally into three groups each of BHS and DS, which were
      euthanized and necropsied at 4, 12, and 18 h post-inoculation (hpi). Bacterial
      and leukocyte counts were performed on broncho-alveolar lavage fluid (BALF)
      collected at necropsy. BALF from BHS euthanized at 4 and 12 hpi contained a
      significantly higher number of M. haemolytica than that from DS. More
      importantly, DS did not have any bacteria in BALF at 18 hpi, while the BHS still
      had significant numbers. As expected, the BHS did exhibit more extensive lung
      lesions at 12 and 18 hpi when compared to DS. At 18 hpi, necrotic PMNs were
      observed in the lesional lung tissues of BHS, but not DS. Furthermore, BALF from
      BHS had significantly lower titers of antibodies to Lkt and surface antigens of
      M. haemolytica, than that of DS. These findings suggest that the enhanced
      pathology in BHS lungs is due to defective clearance of M. haemolytica from the
      lungs.

PMID- 21742447
TI  - Strain-dependent arthritogenic potential of the zoonotic pathogen Corynebacterium
      ulcerans.
AB  - During the last decade the majority of diphtheria cases in Europe had
      Corynebacterium ulcerans as the etiologic agent with dogs and cats as the
      reservoir hosts. However, little has been documented about the virulence factors
      of this zoonotic pathogen. To set up an in vivo experimental C. ulcerans
      infection model, conventional Swiss Webster mice were intravenously infected with
      different doses (from 1 * 10(7) to 5 * 10(9) bacteria per mouse) of C. ulcerans
      strains, namely 809 (from human lower respiratory tract), BR-AD22 (from
      asymptomatic dog nares) and CDC-KC279. Mortality rates were demonstrated by
      LD(50) values ranging from 1.9 * 10(8) to 1.3 * 10(9). Viable bacteria were
      recovered from blood, kidneys, liver, spleen and joints. For CDC-KC279 and 809
      strains (2 * 10(8)mL(-1)) approximately 85% and 72% of animals with articular
      lesions were observed, respectively; BR-AD22-infected mice showed no signs of
      arthritis. CDC-KC279 and 809 strains exhibited higher arthritogenic potential
      when compared to the homologous toxigenic (ATCC27012) and non-toxigenic
      (ATCC27010) strains of Corynebacterium diphtheriae. A high number of affected
      joints and arthritis index in addition to the histopathological features,
      including subcutaneous edema, inflammatory infiltrate, damage to bone tissue and
      synoviocyte hypertrophy, indicated a strain-dependent ability of C. ulcerans
      strains to cause severe polyarthritis. A correlation between the arthritis index
      and systemic levels of IL-6 and TNF-alpha was observed for C. ulcerans strains,
      with the exception of the non-arthritogenic BR-AD22 strain. In conclusion, C.
      ulcerans revealed a strain-dependent arthritogenic potential independent of
      DNAse, PLD and diphtheria toxin production.

PMID- 21742448
TI  - A case of anti-GA1 antibody-positive Fisher syndrome with elevated tau protein in
      cerebrospinal fluid.
AB  - We describe a boy with Fisher syndrome. He presented the typical symptoms of
      Fisher syndrome, including external ophthalmoplegia, abnormality of convergence,
      and areflexia, after an episode of Campylobacter enterocolitis. Atypically,
      however, anti-GA1 antibody was detected in his serum, though anti-GQ1b and anti
      GT1a antibodies were not. In addition, the tau protein level in his cerebrospinal
      fluid was elevated. Generally, Fisher syndrome is a self-limiting disease and has
      a good prognosis. In our patient, however, mild diplopia and areflexia persisted
      6 months after their onset. Here, we report on the first Fisher syndrome patient
      with anti-GA1 antibody in the serum and elevated tau protein in the cerebrospinal
      fluid.

PMID- 21742449
TI  - [Peripheral arterial involvement in giant cell arteritis: how to differentiate
      between atheroma and inflammation?].
AB  - Giant cell arteritis (Horton's disease) is an inflammatory arteritis involving
      medium and large diameter arteries. The disease typically occurs in patients aged
      50 years or more who may otherwise have atherothrombotic lesions. It is sometimes
      difficult to determine whether an arterial stenosis arises from an inflammatory
      or an atherothrombotic mechanism in a patient with giant cell arteritis.
      Therefore we describe, through a case report, the clinical features and
      complementary investigation data helpful for distinguishing between these two
      entities.

PMID- 21742450
TI  - [Chronic compartmental syndrome. a review of 234 patients].
AB  - OBJECTIVE: Diagnosis of chronic compartment syndrome of the lower leg, which
      occurs in a young and athletic population, is often delayed. We studied
      postoperative outcomes after fasciotomy in patients with compartment syndrome in
      order to identify specific postoperative complications. Long-term functional
      outcomes were also evaluated. METHODS: All patients with a diagnosis of chronic
      exercise-related compartment syndrome of the lower leg who underwent surgery from
      January 1985 to August 2009 were studied prospectively. The type of compartment
      and whether surgery was uni or bilateral was recorded. One year after surgery,
      patients completed a questionnaire to evaluate their functional outcome. RESULTS:
      Two hundred and thirty-six compartment procedures were performed in 234 patients.
      Only one compartment (constantly the superficial posterior compartment) was
      treated in 56/236 (23.7%) procedures. Two compartments (anterior and lateral)
      were involved in 90/236 procedures (38.1%). Three compartments (anterolateral and
      superficial posterior) were noted in 74/236 procedures (31.4%) and four
      compartments (anterolateral and superficial and deep posterior) were described in
      6.8%. Involvement of the deep posterior compartment was always associated with
      another compartment. Surgery was bilateral in 70% of patients. The questionnaire
      response rate was 65%. The success rate of fasciotomy was 68.4% and a significant
      improvement was reported by 23.9% of responders; outcome was unsatisfactory for
      7.7%. CONCLUSIONS: The diagnostic criteria used to confirm chronic exercise
      related compartment syndrome of the lower leg were based on the compartment
      pressure measurement after exercise. In this study, all patients underwent
      fasciotomy. The surgical technique was standardized. Outcomes have been
      satisfactory with few surgical complications.

PMID- 21742451
TI  - [A modified Gritti-Stokes amputation for vascular indications in the elderly:
      futility or utility?].
AB  - AIM: Major lower limb amputation in elderly patients is a dreaded event with high
      mortality and morbidity. Peripheral arterial disease is the nearly exclusive
      etiology. The aim of this retrospective study was to assess the feasibility of
      through-knee amputation, and the morbidity and mortality risk in the elderly (>65
      years). PATIENTS AND METHODS: From January 2000 to October 2010, 65 Gritti-Stokes
      through-knee amputations were performed in 58 patients (30 women, 28 men; mean
      age 79 years). Acute limb ischemia was the most common cause (40%). The others
      indications were: severe peripheral arterial disease with extensive necrotic
      lesions (19%), diabetic foot ulcers (15%), non-healing below-knee amputation
      (10%) and vascular graft infection after prosthetic lower extremity bypass
      surgery (6%). RESULTS: Overall 30-day mortality was 24% (n=14/58). Vascular
      morbidity was 9% (n=6/65). The mean hospital stay was 31 days (range 3 to 96).
      The overall healing rate was 78% (n=51/65). Conversion to above-knee amputation
      for failed Gritti-Stokes amputation was performed in one patient. CONCLUSION:
      Gritti-Stokes amputation is feasible in the elderly with an acceptable one-month
      mortality and a satisfactory overall healing rate. Most amputations are
      necessitated by complications of acute limb ischemia. For this subpopulation,
      Gritti-Stokes amputation should be the standard amputation level. The data
      collected in this study provide important information that can be useful before
      amputation for this population, their families and primary care physicians.
      Ambulation is an important postoperative goal and a multidisciplinary approach in
      specialized centers is required to achieve good wound healing rates.

PMID- 21742452
TI  - Intramammary incidental findings on staging computer tomography.
AB  - PURPOSE: Incidental findings are a common feature in computer tomographic
      examinations of the chest. Breast incidentalomas, however, were described only
      sporadically. The purpose of this study was to evaluate retrospectively
      incidental breast findings and to compare radiological features of benign and
      malignant breast lesions. MATERIALS AND METHODS: From January 2006 to December
      2010 a total of 8105 computer tomographic examinations were performed at our
      institution. In 89 patients incidental breast lesions were diagnosed. 64 of the
      identified patients were referred for further clinical, radiological, and
      hystopathological examination. All patients were female with a median age of 62
      years, range 39-82 years. RESULTS: A total of 98 breast lesions were identified
      in the 64 patients. The mean size was 12.0+/-8.0 mm. Primary breast carcinoma was
      identified in 9, breast metastases in 27, and benign findings in 28 patients.
      Malignant lesions demonstrated more often marked enhancement and showed a higher
      density compared with benign lesions. Benign findings were more often lobular in
      shape and had spiculated margins. Most of the breast metastases were round or
      oval in shape with circumscribed margins and marked homogenous enhancement. There
      was no significant difference between the breast cancer and benign findings
      groups in the characteristics of the lesions. CONCLUSION: The breast is a very
      important region and should be carefully evaluate on chest CT. There are no
      certain radiological criteria to differentiate between malignant and benign
      breast lesions on CT. Therefore all breast incidentalomas should be evaluated by
      further radiological/histological investigations.

PMID- 21742453
TI  - MRI of fat necrosis of the breast: the "black hole" sign at short tau inversion
      recovery.
AB  - OBJECTIVE: To describe MRI features of fat necrosis of the breast. MATERIALS AND
      METHODS: Twenty-five lesions in 16 patients were retrospectively analyzed. MRI
      was performed due to equivocal findings at conventional imaging after surgical
      treatment of cancer (n=14) or during anticoagulant therapy (n=1), after focal
      mastitis treated with ductal resection (n=1). In the 15 patients with previous
      surgery MRI was performed after a median interval of 24 months, using short tau
      inversion recovery (STIR) and contrast-enhanced dynamic T1-weighted sequences.
      Signal-to-noise ratio (SNR) inside the lesion and surrounding healthy fat was
      calculated on both STIR and unenhanced T1-weighted images. Maximal lesion
      diameter was measured on STIR images. All lesions had final clinical and imaging
      assessment in favor of fat necrosis and negative clinical and imaging follow-up
      (21-40 months; median 24 months). RESULTS: At STIR sequence, fat necrosis
      appeared as a "black hole", being markedly hypointense (median SNR=29) compared
      with surrounding fat (median SNR=95) (P<0.001), while no significant difference
      was found at unenhanced T1-weighted sequence. No significant correlation with
      time from treatment was found. Of 25 lesions, 15 showed ring enhancement, with
      continuous increase (n=10), plateau (n=2), or wash-out curve (n=3). The 11
      enhancing lesions in the 8 patients with previous radiation therapy showed an
      initial enhancement higher than that of the 4 enhancing lesions in the 2 patients
      who did not, although the difference was not significant (P=0.104). CONCLUSION:
      Fat necrosis of the breast exhibits a "black hole" sign on STIR images, allowing
      for an easier diagnosis in clinical practice.

PMID- 21742454
TI  - Phenotypic and phylogenetic characterization of native peanut Bradyrhizobium
      isolates obtained from Cordoba, Argentina.
AB  - Peanut is an economically important legume nodulated by slow-growing bacteria of
      the genus Bradyrhizobium. In this study, a collection of native slow-growing
      peanut rhizobial isolates from Argentina was obtained and characterized. The
      phenotypical characterization included the determination of the symbiotic
      properties, whereas the genetic and phylogenetic diversity was assessed through
      ERIC-PCR and sequencing of the internal transcribed spacer (ITS) region, as well
      as the dnaK and nodA genes. The results obtained indicated that peanut nodulating
      bradyrhizobia were phenotypically and genotypically diverse, and included locally
      adapted variants of B. yuanmingense and B. iriomotense carrying novel nodA
      alleles.

PMID- 21742455
TI  - Simultaneous determination of creatine and guanidinoacetate in plasma by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS).
AB  - BACKGROUND: Guanidinoacetate (GAA) and creatine are reliable biochemical markers
      for primary and secondary creatine defects. We describe a method by liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS) for simultaneous
      determination of plasma GAA and creatine. We analyzed 283 healthy subjects from 0
      to 63 years old to obtain age-related control values. METHODS: Plasma samples
      were extracted with acetonitrile containing 13C2-GAA and d3-creatine. Samples
      were analyzed by LC-MS/MS in positive ionisation mode, after derivatization to
      butyl-esters. Optimal chromatographic separation was achieved using a column
      SupelcosilTM LC-4.6mm with isocratic elution in 5min. RESULTS: Run time was 5min.
      Standard curves were linear from 0.05 to 200MUmol/L for creatine and from 0.02 to
      40MUmol/L for GAA. Limit of detection (LOD) and limit of quantitation (LOQ) were
      respectively 0.005 and 0.05MUmol/L for creatine; LOD and LOQ were 0.002 and
      0.02MUmol/L respectively for GAA. Intra and inter-assay CVs for creatine and GAA
      were <8%. Recovery experiments adding 50 and 100MUmol/L creatine and 10 and
      20MUmol/L GAA were 102.1% and 101.2%, for creatine; 102.95% and 96.45% for GAA.
      The method was applied to 283 plasma controls from healthy subjects to obtain
      control values in three specific age ranges: 0-12, 13-20, >20 years old.
      CONCLUSION: A rapid and high sensitive LC-MS/MS method was developed and
      validated for determination of creatine and GAA in plasma and it could also be
      applied to other biological materials, such as CFS and urines. This method is
      useful for diagnoses of primary and also for secondary creatine defects that may
      occur in inherited metabolic diseases in which precursors of creatine
      biosynthesis are involved.

PMID- 21742456
TI  - Development and validation of a liquid chromatographic method for the
      simultaneous determination of aniracetam and its related substances in the bulk
      drug and a tablet formulation.
AB  - Simultaneous determination of aniracetam and its related impurities (2
      pyrrolidinone, p-anisic acid, 4-p-anisamidobutyric acid and (p-anisoyl)-4-methyl
      2-pyrrolidinone) was accomplished in the bulk drug and in a tablet formulation
      using a high performance liquid chromatographic method with UV detection.
      Separation was achieved on a Hypersil BDS-CN column (150 mm * 4.0 mm, 5 MUm)
      using a gradient elution program with solvent A composed of phosphate buffer (pH
      4.0; 0.010 M) and solvent B of acetonitrile-phosphate buffer (pH 4.0; 0.010 M)
      (90:10, v/v). The flow rate of the mobile phase was 1.0 mL min(-1) and the total
      elution time, including the column re-equilibration, was approximately 20 min.
      The UV detection wavelength was varied appropriately among 210, 250 and 280 nm.
      Injection volume was 20 MUL and experiments were conducted at ambient
      temperature. The developed method was validated in terms of system suitability,
      selectivity, linearity, range, precision, accuracy, limits of detection and
      quantification for the impurities, short term and long term stability of the
      analytes in the prepared solutions and robustness, following the ICH guidelines.
      Therefore, the proposed method was suitable for the simultaneous determination of
      aniracetam and its studied related impurities.

PMID- 21742457
TI  - Chronic malnutrition may in fact be an acute emergency.
AB  - BACKGROUND: Reintroduction of nutrition to the chronically starved patient
      presents a constellation of metabolic challenges termed "refeeding syndrome." The
      consequences of this syndrome--principally hypophosphatemia--may be life
      threatening. Although previously described in the nutritional literature, little
      information exists on this syndrome written from the perspective of the emergency
      physician. OBJECTIVES: To promote the early use of prophylactic electrolyte
      replacement in patients at risk of refeeding syndrome. CASE REPORT: We present
      the case of a 32-year-old woman with self-inflicted starvation who developed
      severe hypophosphatemia, hypocalcemia, and hypomagnesemia due to unintended
      refeeding in the emergency department (ED). CONCLUSIONS: The acute complications
      of refeeding syndrome may present during a patient's stay in the ED or during the
      transition from the ED to a critical care area, and thus this syndrome deserves
      consideration from the moment a starved patient presents to our triage desks.

PMID- 21742458
TI  - Steeple sign: not specific for croup.

PMID- 21742459
TI  - The use of cephalosporins in penicillin-allergic patients: a literature review.
AB  - BACKGROUND: The practice of avoiding cephalosporin administration to penicillin
      allergic patients persists despite the low rate of cross reactions between both
      groups of antibiotics. OBJECTIVE: The purpose of this literature review is to
      evaluate the published evidence regarding the commonly held belief that patients
      with a history of an allergic reaction to penicillin have a significantly
      increased risk of an allergic reaction to cephalosporins. MATERIALS AND METHODS:
      Articles were identified through a computerized search of MEDLINE from 1950 to
      the present using the search terms "penicillin$," "cephalosporin$," "allerg$,"
      "hypersensitivity," and "cross-react$." All articles were reviewed, and
      additional sources cited in them were added to the literature review. RESULTS:
      Penicillins have a cross allergy with first-generation cephalosporins (odds ratio
      4.8; confidence interval 3.7-6.2) and a negligible cross allergy with second
      generation cephalosporins (odds ratio 1.1; confidence interval 0.6-2.1).
      Laboratory and cohort studies confirm that the R1 side chain is responsible for
      this cross reactivity. Overall cross reactivity between penicillins and
      cephalosporins is lower than previously reported, though there is a strong
      association between amoxicillin and ampicillin with first- and second-generation
      cephalosporins that share a similar R1 side chain. CONCLUSIONS: Although a myth
      persists that approximately 10% of patients with a history of penicillin allergy
      will have an allergic reaction if given a cephalosporin, the overall cross
      reactivity rate is approximately 1% when using first-generation cephalosporins or
      cephalosporins with similar R1 side chains. However, a single study reported the
      prevalence of cross reactivity with cefadroxil as high as 27%. For penicillin
      allergic patients, the use of third- or fourth-generation cephalosporins or
      cephalosporins with dissimilar side chains than the offending penicillin carries
      a negligible risk of cross allergy.

PMID- 21742460
TI  - A systematic review of interventions for co-occurring substance use disorder and
      borderline personality disorder.
AB  - Rates of borderline personality disorder (BPD) among individuals with substance
      use disorder (SUD) are estimated to be as high as 65%. Such elevated rates
      present considerable challenges for drug treatment services given that
      individuals with co-occurring SUD and BPD have higher rates of relapse, treatment
      noncompliance, and poorer outcomes than those with either diagnosis alone. A
      systematic review investigating current treatment options for co-occurring SUD
      and BPD was conducted using Medline and PsycINFO. Randomized controlled trials
      were the focus. Six studies were included that examined the use of three
      psychosocial therapies: dialectical behavior therapy, dual focused schema therapy
      and dynamic deconstructive psychotherapy. Despite all studies demonstrating some
      treatment gains over time, there is currently insufficient evidence to recommend
      one treatment over another. Further research is needed to examine effective
      treatment options for co-occurring SUD and BPD, especially those that are likely
      to be applicable in mainstream drug treatment settings.

PMID- 21742461
TI  - [Perioperative assessment of cardiac risk patient in non-cardiac surgery].

PMID- 21742462
TI  - [Dental trauma and anaesthesiology: epidemiology and insurance-related impact
      over 4 years in Rouen teaching hospital].
AB  - OBJECTIVES: Dental injuries are the first cause of sinistrality in
      anaesthesiology. However, few insurance-related data are available concerning the
      publicly-owned establishments, in particular on the cost of the complaints
      deposited. We studied the epidemiology of dental trauma in a teaching hospital
      and brought it closer to the induced insurance-related costs. PATIENTS AND
      METHODS: We conducted a retrospective study, examining the files of declaration
      of dental trauma, from January 2005 to December 2008. The litigations for dental
      injuries treated by Quality and Services Department were also analysed. RESULTS:
      Seventy-two cases of dental lesions were declared, i.e. 1/1528 general
      anaesthesias. Concerning the risk factors of lesion, 47 patients (65%) presented
      bad dental conditions identified during the pre-anaesthetic consultation; 27
      patients (37%) had criteria for difficult intubation listed on the sheet of
      anaesthesia. The association of the 2 factors was found among 20 patients. The
      indication of information to the patient on the dental risk was registered on the
      sheet of anaesthesia in 17% of cases. The Quality and Services Department
      recorded 23 complaints for dental trauma over the period. In 4 cases the
      complaint was followed by a compensation for an average amount equal to 608 (256
      1002) Euros, i.e., a total cost of 2434 Euros. CONCLUSIONS: The two main risk
      factors of dental lesion are well identified with the consultation of anaesthesia
      and are noted on the file. However, information to the patient on this risk is
      seldom notified. The incidence of dental lesions is important, but few complaints
      open right to financial repair for a very low insurance-related total amount.

PMID- 21742463
TI  - Acute effect of TSH on oxygenation state and volume of erythrocytes from subjects
      thyroidectomized for differentiated thyroid carcinoma.
AB  - We previously reported the presence in the membrane erythrocyte of a TSH receptor
      (TSHR), a G-protein coupled receptor, which responds to TSH with increased cAMP
      level. Since there is evidence for a role of G protein receptors as oxygen
      sensor(s) implicated in cell volume regulation, we hypothesized that erythrocyte
      TSHR, by TSH stimulation, could modify the erythrocyte volume and the oxygenation
      state of erythrocytes. We determined the effect of TSH on the gas analysis in 35
      thyroidectomized patients for stage I differentiated thyroid cancer enrolled for
      recombinant human thyroid-stimulating hormone (rhTSH) test during chronic
      treatment with synthetic l-thyroxine. Moreover, we explored the influence of TSH
      on the shape of erythrocytes. Venous blood-gas analysis before and after TSH were
      determined with a pH/blood gas electrolyte and 682 CO-Oxymeter. In a subgroup of
      subjects (n=10), the isolated red blood cells (RBC) were analyzed by flow
      cytometry for morphological changes. After TSH stimulation, we found a
      significant decrease in PCO(2) (P<0.001), an increase in pH (P<0.01) and an
      increase of % O(2)-Hb (P<0.05) and pO(2) (P<0.05). By flow cytometry, the
      erythrocytes after TSH showed a significant enrichment on the mean number in the
      selected region R1 corresponding to bigger volumes (P<0.05, n=10). Finally, by
      contrast phase microscopy, when the cell area was measured, a mean increased
      volume was observed in erythrocytes after TSH compared to the basal before TSH
      (P<0.05). In conclusion, our results indicate that acute stimulation of TSH by
      rhTSH modifies the oxygenation state and volume of erythrocyte.

PMID- 21742464
TI  - [Necrotising community-acquired pneumonia due to Panton-Valentine leukocidin
      secreting Staphylococcus aureus: a rare diagnosis to be evoked].

PMID- 21742465
TI  - Lipid lowering on progression of mild to moderate aortic stenosis: meta-analysis
      of the randomized placebo-controlled clinical trials on 2344 patients.
AB  - BACKGROUND: Aortic stenosis (AS) is believed to develop through an inflammatory
      similar to the atherosclerosis process. Based on findings from animal studies and
      uncontrolled clinical studies, lipid-lowering therapy with a statin is postulated
      to slow this process. Randomized trials, however, reported neutral results. This
      meta-analysis of randomized lipid trials on patients with AS examined the effects
      of treatment on AS progression and clinical outcomes. METHODS: Echocardiographic
      measures of AS (aortic valve jet velocity, peak and mean valve gradients, and
      aortic valve area) were pooled and clinical outcomes were evaluated in 4
      randomized placebo controlled trials (N=2344). RESULTS: Although active treatment
      with statin therapy was associated with highly significant 50% reduction in low
      density lipoprotein cholesterol levels, there were no statistical differences
      between active and placebo groups in any of the echocardiographic indicators of
      AS severity: annual increase in AS velocity was 0.16+/-0.28 m/sec, and mean
      gradient was 2.8+/-3.0 mm Hg. Each trial reported no differences in clinical
      outcomes between the 2 treatment groups. Substantial events rates (6.6% aortic
      valve surgery and 1.2% cardiovascular deaths per year in SEAS with follow-up of
      4.4 years and 5.8% aortic valve surgery and 0.7% cardiovascular deaths per year
      in ASTRONOMER over 3.5 years) were observed in these patients despite the
      relatively mild disease. CONCLUSION: The current data do not support the
      hypothesis that statin therapy reduces AS progression. Patients with mild to
      moderate AS may require closer follow-up because despite the less severe disease
      in these trials, event rates remain substantial.

PMID- 21742466
TI  - The clinical profile and outcomes associated with coronary collaterals in
      patients with coronary artery disease.
AB  - BACKGROUND: The clinical correlates of coronary collaterals and the effects of
      coronary collaterals on prognosis are incompletely understood. METHODS: We
      performed a study of 55,751 patients undergoing coronary angiography to evaluate
      the correlates of angiographically apparent coronary collaterals, and to evaluate
      their association with survival. RESULTS: The characteristic most strongly
      associated with the presence of collaterals was a coronary occlusion (odds ratio
      [OR], 28.9; 95% confidence interval [CI], 27.1-30.6). Collaterals were associated
      with improved adjusted survival overall (hazard ratio [HR] 0.89; 95% CI, 0.85
      0.95), and in both acute coronary syndrome (ACS) (HR 0.90; 95% CI, 0.84-0.96) and
      non-ACS (HR 0.84; 95% CI, 0.77-0.92) patients. Collaterals were associated with
      improved survival in those receiving angioplasty (HR 0.78; 95% CI, 0.71-0.85) and
      those with low risk anatomy treated medically (HR 0.84; 95% CI, 0.72-0.98), but
      not for those treated with coronary bypass graft surgery or those with high-risk
      anatomy treated without revascularization. CONCLUSIONS: The major correlate of
      coronary collaterals is the presence/extent of obstructive coronary artery
      disease. Collaterals are associated with better survival overall and in both ACS
      and non-ACS presentations, but not for those treated with coronary artery bypass
      graft (CABG) or those with high-risk anatomy who are not revascularized.

PMID- 21742467
TI  - Motivating children with developmental coordination disorder in school physical
      education: the self-determination theory approach.
AB  - The purpose of the current article is to highlight the potential of self
      determination theory (SDT) to inform the teaching practices of physical education
      (PE) teachers. Such practices may enhance motivational levels for participation
      in physical activity (PA) for children with developmental coordination disorder
      (DCD). First, we review the research in PE demonstrating links between teachers'
      interpersonal style, teaching methods, and outcomes relating to both students'
      motivation and motor skill improvement. Second, we outline the SDT mechanism
      through which the practices employed by PE teachers to support students'
      psychological needs for autonomy, competence, and relatedness may effect positive
      changes in the motivation and the physical activity behaviour of children with
      DCD. Third, we present an overview of findings on the effectiveness of need
      supporting practices used by PE teachers. Fourth, we provide directions for
      future motivational research using the SDT principles in school physical
      education for children with DCD.

PMID- 21742468
TI  - Effects of age, intelligence and executive control function on saccadic reaction
      time in persons with intellectual disabilities.
AB  - The current research aimed to clarify the influence of age, intelligence and
      executive control function on the central tendency and intraindividual
      variability of saccadic reaction time in persons with intellectual disabilities.
      Participants were 44 persons with intellectual disabilities aged between 13 and
      57 years whose IQs were between 14 and 70. Executive control function was
      evaluated by a test of sustained simple motor action. To elicit saccades, a
      predictive visually guided saccade paradigm was used. Intelligence and executive
      control function were significantly associated with saccadic reaction time. The
      central tendency of saccadic reaction time was negatively correlated with
      intelligence. The more serious the degree of executive control dysfunction was,
      the larger the intraindividual variability of saccadic reaction time. It is
      thought that intelligence and executive control function have relatively
      independent influences on saccadic reaction time. However, there is a possibility
      that the increase of intraindividual variability in saccadic reaction time due to
      the problem of executive control function extends the central tendency of
      saccadic reaction time.

PMID- 21742469
TI  - Behavioral interventions for rumination and operant vomiting in individuals with
      intellectual disabilities: a systematic review.
AB  - We conducted a systematic analysis of studies that involved the treatment of
      rumination and operant vomiting in individuals with developmental disabilities. A
      total of 21 studies involving a combined 32 participants were identified and
      analyzed in terms of (a) participant characteristics, (b) dependent variables,
      (c) intervention procedures, (d) functional assessment procedures and results,
      (e) intervention outcomes, and (f) certainty of evidence. In comparison to
      previous reviews on rumination and operant vomiting, this review identified fewer
      studies involving punishment-based interventions and an increase in function
      based reinforcement interventions. Preliminary guidelines for practitioners faced
      with assessing and treating these behaviors are offered and directions for future
      research are discussed.

PMID- 21742470
TI  - Prediction of participation and sensory modulation of late preterm infants at 12
      months: a prospective study.
AB  - The aim of the study was to prospectively assess the differences in participation
      and sensory modulation between late preterm infants (LPI) and term babies, and to
      predict it by LPI characteristics. The study population includes 124 late preterm
      infants at gestational age between 34 and 35 6/7 weeks who were born at the same
      medical center. The control group comprised of 33 term babies (18 boys, 15
      girls), born during the same period and location (mean age 12.47, SD = 0.73).
      Sensory modulation was assessed by the test of sensory functions in infants and
      the infant/toddler sensory profile and for assessment of participation and
      parents' satisfaction we used questionnaires. Term infants had better sensory
      modulation than LPI. Approximately 10% of the sensory modulation of participants
      in the study was explained by gestational age and head circumference. LPI
      participation and parental satisfaction decreased in the LPI group. Among all the
      explanatory variables only multiple gestations and head circumference contributed
      to the explained variance of participation (16%), and parents' satisfaction
      (13%). At age of 1 year, children born as late preterm are at increased risk of
      developing sensory modulation disorder, showing less participation, and resulting
      in less parental satisfaction.

PMID- 21742471
TI  - Permeability of anti-fouling PEGylated surfaces probed by fluorescence
      correlation spectroscopy.
AB  - The present work reports on in situ observations of the interaction of organic
      dye probe molecules and dye-labeled protein with different poly(ethylene glycol)
      (PEG) architectures (linear, dendron, and bottle brush). Fluorescence correlation
      spectroscopy (FCS) and single molecule event analysis were used to examine the
      nature and extent of probe-PEG interactions. The data support a sieve-like model
      in which size-exclusion principles determine the extent of probe-PEG
      interactions. Small probes are trapped by more dense PEG architectures and large
      probes interact more with less dense PEG surfaces. These results, and the tunable
      pore structure of the PEG dendrons employed in this work, suggest the viability
      of electrochemically-active materials for tunable surfaces.

PMID- 21742472
TI  - Microbially induced separation of quartz from calcite using Saccharomyces
      cerevisiae.
AB  - Cells of Saccharomyces cerevisiae and their metabolites were successfully
      utilized to achieve selective separation of quartz and calcite through
      microbially induced flotation and flocculation. S. cerevisiae was adapted to
      calcite and quartz minerals. Adsorption studies and electrokinetic investigations
      were carried out to understand the changes in the surface chemistry of yeast
      cells and the minerals after mutual interaction. Possible mechanisms in
      microbially induced flotation and flocculation are outlined.

PMID- 21742473
TI  - Automatic sleep scoring: a search for an optimal combination of measures.
AB  - OBJECTIVE: The objective of this study is to find the best set of characteristics
      of polysomnographic signals for the automatic classification of sleep stages.
      METHODS: A selection was made from 74 measures, including linear spectral
      measures, interdependency measures, and nonlinear measures of complexity that
      were computed for the all-night polysomnographic recordings of 20 healthy
      subjects. The adopted multidimensional analysis involved quadratic discriminant
      analysis, forward selection procedure, and selection by the best subset
      procedure. Two situations were considered: the use of four polysomnographic
      signals (EEG, EMG, EOG, and ECG) and the use of the EEG alone. RESULTS: For the
      given database, the best automatic sleep classifier achieved approximately an 81%
      agreement with the hypnograms of experts. The classifier was based on the next 14
      features of polysomnographic signals: the ratio of powers in the beta and delta
      frequency range (EEG, channel C3), the fractal exponent (EMG), the variance
      (EOG), the absolute power in the sigma 1 band (EEG, C3), the relative power in
      the delta 2 band (EEG, O2), theta/gamma (EEG, C3), theta/alpha (EEG, O1),
      sigma/gamma (EEG, C4), the coherence in the delta 1 band (EEG, O1-O2), the
      entropy (EMG), the absolute theta 2 (EEG, Fp1), theta/alpha (EEG, Fp1), the sigma
      2 coherence (EEG, O1-C3), and the zero-crossing rate (ECG); however, even with
      only four features, we could perform sleep scoring with a 74% accuracy, which is
      comparable to the inter-rater agreement between two independent specialists.
      CONCLUSIONS: We have shown that 4-14 carefully selected polysomnographic features
      were sufficient for successful sleep scoring. The efficiency of the corresponding
      automatic classifiers was verified and conclusively demonstrated on all-night
      recordings from healthy adults.

PMID- 21742474
TI  - Measuring trust in healthcare professionals--a study of ethnically diverse UK
      cancer patients.
AB  - AIM: To assess the effect of patient physician trust on how British South Asian
      (BSA) and British White (BW) patients cope when diagnosed with cancer. MATERIALS
      AND METHODS: We administered a questionnaire incorporating domains of fidelity,
      honesty, competence, confidentiality and global trust. The patient-physician
      relationship most preferred by the patient was tested by a further five
      questions. Five other questionnaires were completed, including the Brief Illness
      Perception Questionnaire and mini-MAC. In total, 94 BSA patients and 185 BW
      patients were recruited in the Leicestershire Cancer Centre by an English
      speaking nurse or two radiographers who between them spoke English, Gujarati,
      Hindi and Urdu. RESULTS: In all the five domains of trust, BW and BSA patients
      rated doctors in the Leicestershire Cancer Centre consistently high or very high;
      97.4% (BW 97.2%, BSA 95.7%) were satisfied with the medical care received and
      94.4% completely trusted the hospital doctor; 9.3% were concerned that 'the NHS
      would not give the best possible care'. Fewer (80.2%) showed a high degree of
      trust in general practitioners, particularly in BSA patients (BW 81.4%, BSA 78%,
      P<0.027). More BSA patients, however, preferred to receive sensitive information
      from their general practitioner (BSA 62.5% versus 32.6%; P<0.0005 or from
      'someone of the similar religion or background to me' (BSA 38.1% versus BW 7.4%;
      P<0.0001). Confidentiality (P=0.0005), faith in treatment (P=0.011) and
      understanding of cancer (P=0.011) plus a low detrimental effect of the illness on
      lives (P=0.0005) were strong predictors of trust in this sample. CONCLUSION:
      Trust in both the hospital, general practitioners and the National Health Service
      in general is very high among BSA and BW cancer patients in Leicestershire.
      Greater partnership between the hospital and general practitioners is desirable
      for some sections of our population.

PMID- 21742475
TI  - Beneficial effects of Psidium guajava leaf extract on diabetic myocardium.
AB  - Non enzymatic glycosylation (glycation) between reducing sugar and protein
      results in the formation of advanced glycation end products (AGEs), which is
      believed to play an important role in diabetes associated cardiovascular
      complications. Thus agents that inhibit the formation of AGEs are believed to
      have therapeutic potential against diabetic complications. In the present study
      we evaluated the antiglycative potential of ethyl acetate fraction of Psidium
      guajava leaves (PGEt) by administering the extract into streptozotocin induced
      diabetic rats. Daily administration of the extract for a period of one month
      significantly decreased the blood glucose, glycated hemoglobin and fructosamine
      levels in a dose dependent manner. Evaluation of the toxicity markers like SGOT
      and SGPT revealed the non toxic nature of the extract. Apart from this we
      evaluated the presence of cardiac isoform of liver alpha 2 macroglobulin, which
      is a major protein associated with earlier stages of cardiac hypertrophy. SDS
      PAGE analysis showed that the level of this protein decreased significantly in
      extract treated groups compared to diabetic control. These findings support that
      the administration of PGEt extract may be beneficial for preventing
      cardiovascular complications associated with diabetes.

PMID- 21742476
TI  - Remodeling of fetoplacental arteries in rats due to chronic hypoxia.
AB  - The increased fetoplacental vascular resistance due to chronic hypoxia cannot be
      explained by simple hypoxic vasoconstriction, as it sustains to some degree after
      recovery in normobaric environment. To verify a hypothesis that fetoplacental
      arteries undergo remodeling of their walls similar to remodeling of pulmonary
      arteries in hypoxic pulmonary hypertension, we used a model of the chronically
      hypoxic rat placenta. Han Wistar pregnant rats were exposed to 14-day hypoxia
      (10% of oxygen) during the 6th to 19th day of pregnancy. Chronic hypoxia elicited
      in both intraplacental (prelabyrinthine) and chorionic plate (insertion) arteries
      significant narrowing of their lumina. Irregular thickening of their adventitia
      due to an increase in collagen fibers as well as ground substance was observed;
      reticular fibers were fragmented. Because of remodeling of fetoplacental
      arteries, a model of chronically hypoxic rat placenta could simulate human
      preplacental hypoxia and consequent effects.

PMID- 21742477
TI  - Angiotensin-converting enzyme polymorphism affects outcome of local Chinese with
      acute lung injury.
AB  - INTRODUCTION: Acute Lung Injury (ALI) with genetic predisposition is fatal.
      Relationship between angiotensin-converting enzyme insertion/deletion (ACE I/D)
      polymorphism and the prognosis of local Chinese patients with ALI was
      investigated; meanwhile, the mechanisms involved were explored. METHODS: 101 ALI
      patients, 408 non-ALI patients and 236 healthy blood donors were enrolled. ACE
      I/D polymorphism was detected by polymerase chain reaction, then ACE genotype
      (II, ID, DD) and allele (I, D) frequencies were compared. Clinical data of ALI
      patients was calculated. Also, peripheral blood mononuclear cells (PBMC) were
      isolated from healthy volunteers with different ACE genotypes. Lipopolysaccharide
      (LPS)-induced ACE gene mRNA expression and ACE activity was measured. RESULTS:
      There was no significant difference in the frequencies of the genotypes and
      alleles. Acute Physiology and Chronic Health Evaluation (APACHE) II score was
      higher in DD subgroup than in II subgroup (19.7 +/- 8.7 and 15.6 +/- 6.2; P <
      0.05). The 28-day mortality was significantly different (17.4%, 26.8%, and 64.3%
      for II, ID, and DD; P = 0.013). DD genotype was the independent prognostic factor
      for 28-day outcome. Furthermore, LPS-induced ACE mRNA expression and ACE activity
      from PBMC in DD genotype subgroup were both significantly higher than those in
      the other two subgroups. CONCLUSIONS: ACE I/D polymorphism is a prognostic factor
      for ALI. Patients with the DD genotype have higher mortality of ALI. Polymorphism
      influences the expression of ACE gene in LPS-stimulated PBMC, DD genotype leads
      to higher level of mRNA and enzyme activity. It may be one of the mechanisms
      involved.

PMID- 21742478
TI  - CPAP increases exercise tolerance in obese subjects with obstructive sleep apnea.
AB  - Obese subjects commonly suffer from exertional dyspnea and exercise intolerance.
      Preliminary evidence suggests that treatment with nocturnal continuous positive
      airway pressure (nCPAP) may improve dyspnea in obese patients with obstructive
      sleep apnea (OSA), but the effect on exercise tolerance is unknown. This study
      sought to investigate whether nCPAP improves exercise tolerance and exertional
      dyspnea in obese patients with OSA. Obese patients prescribed nCPAP for
      moderate/severe OSA and without cardiopulmonary disease were recruited. Patients
      completed a constant-load exercise test and Baseline and Transitional Dyspnea
      Index questionnaires (BDI/TDI) at baseline and after one and three months of
      nCPAP. Primary outcome was change in constant-load exercise time from baseline to
      one and three months. Secondary outcomes included changes in isotime dyspnea,
      isotime leg fatigue and BDI/TDI score at one and three months. Fifteen subjects
      (body mass index = 43 kg m(-2), apnea-hypopnea index = 49(.)hr(-1)) were studied.
      Constant-load exercise time increased by 2.0 min (40%, p = 0.02) at one month and
      1.8 min (36%, p = 0.04) at three months. At one and three months, isotime dyspnea
      decreased by 1.4 (p = 0.17) and 2 units (p = 0.04), and leg fatigue decreased by
      1.2 (p = 0.18) and 2 units (p = 0.02), respectively. BDI/TDI scores were 2.7 (p =
      0.001) and 4.5 points (p < 0.001) at one and three months. Peak oxygen
      consumption and static pulmonary function were unchanged. Nocturnal CPAP improves
      exercise tolerance and dyspnea in obese patients with OSA. Effects on exercise
      time and chronic dyspnea were seen after one and three months of nCPAP, while
      exertional dyspnea was only improved at three months.

PMID- 21742479
TI  - Challenges and opportunities to integrating family members of injection drug
      users into harm reduction efforts within the Atlantic Canadian context.
AB  - BACKGROUND: This paper explores injection drug users' (IDUs) relationships with
      non-drug using family members in order to understand the potential opportunities
      for, and challenges to, having these family members provide harm reduction
      services (e.g., clean syringes). METHODS: The qualitative data for this paper
      were drawn from a larger study of IDUs' relationships with key individuals in
      their lives (e.g., friends, family members). Interviews were conducted with 115
      IDUs from across Atlantic Canada living in both urban and rural areas. RESULTS:
      IDUs report that their relationships with family members are variable and
      dynamic, often changing over time. IDUs and family members engage in a variety of
      strategies to protect themselves from the multiple harms associated with drug
      use. Several strategies of self-protection (e.g., discontinuing all contact) are
      antithetical to the provision of harm reduction supports by family members.
      However, other strategies are based on continued contact, providing a potential
      opportunity for the integration of harm reduction approaches. Some family members
      not only have contact but provide supports (e.g., emotional support, housing)
      thus potentially facilitating the integration of harm reduction. In a few
      instances, family members already provide harm reduction supports (e.g., safe
      space to use). CONCLUSIONS: Conceptualizing addictions as a health and social
      justice issue, and providing appropriate interventions, may reduce some of the
      harms experienced by users and family members thus encouraging sustained
      relationships and greater integration of harm reduction approaches into the
      relationship. Targeted education to family members about harm reduction may also
      further encourage their involvement in such efforts. Likewise, supporting family
      members who are already providing harm reduction supports will likely assist in
      the scaling-up of harm reduction efforts.

PMID- 21742480
TI  - Public sentiment towards alcohol and local government alcohol policies in New
      Zealand.
AB  - BACKGROUND: In many countries, including New Zealand, alcohol availability and
      promotion have increased markedly in the last three decades as a result of
      liberalised central and/or state government alcohol policies. Accordingly,
      communities are increasingly relying on local government to manage alcohol
      related problems. New Zealand's Local Government Act (2002) states the purpose of
      local government as facilitating public decision-making and promoting community
      well-being. We sought to describe public sentiment towards alcohol and local
      government alcohol policies. METHODS: A cross-sectional survey was conducted in
      2007 with a sample of 2337 residents aged 18 years and over in a diverse set of
      New Zealand communities. Data were collected via a self-administered pen-and
      paper questionnaire. RESULTS: There were responses from 1372 individuals
      (response: 59%). Problem drinking amongst youth (<25 years of age) was considered
      the leading problem by the majority of respondents in six of seven areas. Alcohol
      was considered to play a major role in incidents of violence, vandalism,
      dangerous driving and traffic crashes. Fifty-eight percent of respondents agreed
      that "it is up to local government to make sure alcohol does not become a problem
      in the community". There was strong support for local governments to restrict the
      hours of operation of on-licenced premises, to use liquor bans to control
      drinking in public places, and for local governments and police to be stricter in
      their enforcement of drinking laws. CONCLUSION: There is strong support for local
      government alcohol policies that restrict the availability and promotion of
      alcohol. The study findings are important in light of the stated purpose of local
      government in New Zealand and the recently completed "once in a generation"
      review of alcohol laws and policies.

PMID- 21742481
TI  - Are drug detection dogs and mass-media campaigns likely to be effective policy
      responses to psychostimulant use and related harm? Results from an agent-based
      simulation model.
AB  - BACKGROUND: Agent-based simulation models can be used to explore the impact of
      policy and practice on drug use and related consequences. In a linked paper
      (Perez et al., 2011), we described SimAmph, an agent-based simulation model for
      exploring the use of psychostimulants and related harm amongst young Australians.
      METHODS: In this paper, we use the model to simulate the impact of two policy
      scenarios on engagement in drug use and experience of drug-related harm: (i) the
      use of passive-alert detection (PAD) dogs by police at public venues and (ii) the
      introduction of a mass-media drug prevention campaign. RESULTS: The findings of
      the first simulation suggest that only very high rates of detection by PAD dogs
      reduce the intensity of drug use, and that this decrease is driven mainly by a
      four-fold increase in negative health consequences as detection rates rise. In
      the second simulation, our modelling showed that the mass-media prevention
      campaign had little effect on the behaviour and experience of heavier drug users.
      However, it led to reductions in the prevalence of health-related conditions
      amongst moderate drug users and prevented them from becoming heavier users.
      CONCLUSION: Agent-based modelling has great potential as a tool for exploring the
      reciprocal relationships between environments and individuals, and for
      highlighting how intended changes in one domain of a system may produce
      unintended consequences in other domains. The exploration of these linkages is
      important in an environment as complex as the drug policy and intervention arena.

PMID- 21742482
TI  - Environmental implications of nanomaterials: are we studying the right thing?
AB  - A fundamental lack of data on the potential impacts of carbon based nanomaterials
      on natural ecosystems currently exists. The gap between what we know about
      environmental impacts and new products that may contain nanomaterials continues
      to get wider especially related to knowledge about nanocomposites. In this paper
      we present ideas and concerns about the current state of knowledge on
      nanomaterials in the environment and present a number of points about what recent
      work has provided us about the novel materials.

PMID- 21742483
TI  - Biotechnological synthesis of functional nanomaterials.
AB  - Biological systems, especially those using microorganisms, have the potential to
      offer cheap, scalable and highly tunable green synthetic routes for the
      production of the latest generation of nanomaterials. Recent advances in the
      biotechnological synthesis of functional nano-scale materials are described.
      These nanomaterials range from catalysts to novel inorganic antimicrobials,
      nanomagnets, remediation agents and quantum dots for electronic and optical
      devices. Where possible, the roles of key biological macromolecules in
      controlling production of the nanomaterials are highlighted, and also
      technological limitations that must be addressed for widespread implementation
      are discussed.

PMID- 21742484
TI  - Neural processing as causal inference.
AB  - Perception is about making sense, that is, understanding what events in the
      outside world caused the sensory observations. Consistent with this intuition,
      many aspects of human behavior confronting noise and ambiguity are well explained
      by principles of causal inference. Extending these insights, recent studies have
      applied the same powerful set of tools to perceptual processing at the neural
      level. According to these approaches, microscopic neural structures solve
      elementary probabilistic tasks and can be combined to construct hierarchical
      predictive models of the sensory input. This framework suggests that variability
      in neural responses reflects the inherent uncertainty associated with sensory
      interpretations and that sensory neurons are active predictors rather than
      passive filters of their inputs. Causal inference can account parsimoniously and
      quantitatively for non-linear dynamical properties in single synapses, single
      neurons and sensory receptive fields.

PMID- 21742485
TI  - Survival advantage for irinotecan versus best supportive care as second-line
      chemotherapy in gastric cancer--a randomised phase III study of the
      Arbeitsgemeinschaft Internistische Onkologie (AIO).
AB  - BACKGROUND: The value of second-line therapy for metastatic gastric cancer is
      unclear. So far there are no randomised phase III data comparing second-line
      chemotherapy to best supportive care (BSC). In this prospective, multicenter,
      open label, randomised phase III study we compared irinotecan to BSC to evaluate
      the impact on survival of second-line chemotherapy. METHODS: Eligible patients
      (pts) had metastatic or locally advanced gastro-oesophageal junction or gastric
      adenocarcinoma, objective tumour progression during or within 6months after first
      line chemotherapy and ECOG performance status 0-2. Stratification for time of
      progression after first-line therapy, ECOG PS and pretreatment secured even
      distribution of important prognostic factors. TREATMENT: Arm A: Irinotecan
      250mg/m(2)q3w (first cycle) to be increased to 350mg/m(2), depending on toxicity.
      Arm B: BSC. FINDINGS: Between 10/2002 and 12/2006 40 pts were randomised. The
      study was closed prematurely due to poor accrual. Responsefor arm A (19 pts
      evaluable): No objective responses, SD 53%, PD 47%. Improvement of tumour related
      symptoms: Arm A 50% of pts, arm B 7%. Overall Survival: (all events in 40 pts
      have occurred): The hazard ratio for death was reduced to 0.48 (95%CI 0.25-0.92)
      in the irinotecan-arm (p=0.012). Median survival arm A: 4.0months (95% CI 3.6
      7.5), arm B: 2.4months (95% CI 1.7-4.9). INTERPRETATION: Irinotecan as second
      line chemotherapy significantly prolongs overall survival compared to BSC in the
      studied pts. Second-line chemotherapy can now be considered as a proven treatment
      option for metastatic or locally advanced gastric cancer. FUNDING: The study was
      supported by a research grant from Aventis and Pfizer.

PMID- 21742486
TI  - Enhanced production of bioethanol and ultrastructural characteristics of reused
      Saccharomyces cerevisiae immobilized calcium alginate beads.
AB  - Yeast immobilized on alginate beads produced a higher ethanol yield more rapidly
      than did free yeast cells under the same batch-fermentation conditions. The
      optimal fermentation conditions were 30 degrees C, pH 5.0, and 10% initial
      glucose concentration with 2% sodium alginate beads. The fermentation time using
      reused alginate beads was 10-14 h, whereas fresh beads took 24h, and free cells
      took 36 h. All bead samples resulted in nearly a 100% ethanol yield, whereas the
      free cells resulted in an 88% yield. Transmission electron microscopy (TEM)
      showed that the shortened time and higher yield with the reused beads was due to
      a higher yeast population per bead as well as a higher porosity. The
      ultrastructure of calcium alginate beads and the alginate matrix structure known
      as the "egg-box" model were observed using TEM.

PMID- 21742487
TI  - Influence of humic substances on bioavailability of Cu and Zn during sewage
      sludge composting.
AB  - Influence of humic substances (HS) on bioavailability of Cu and Zn was
      characterized during 120 days co-composting of sewage sludge and maize straw. At
      the initial stage of composting, Cu and Zn in sewage sludge were released as
      organic matter was degraded, and water soluble Cu and Zn increased markedly.
      Water soluble Cu and FA content decreased after 21 days whereas water soluble Zn
      increased during the whole process. Both HA-Cu and HA-Zn were significantly and
      positively correlated with HA and H/F, respectively. At the end of composting,
      the distribution coefficients of HA-Cu and HA-Zn reached 27.50% and 3.33%
      respectively with HA-Cu/HA-Zn ratio increased from 1.29 to 2.73. The results
      suggest that Cu combined with HA more strongly than Zn, and composting treatment
      could decrease bioavailability of Cu markedly.

PMID- 21742488
TI  - Microwave pretreatment of rape straw for bioethanol production: focus on energy
      efficiency.
AB  - The energy efficiency of microwave-assisted dilute sulfuric acid pretreatment of
      rape straw for the production of ethanol was investigated. Different microwave
      energy inputs and solid loadings were tested to find economic pretreatment
      conditions. The lowest energy consumption was observed when solid loading and
      energy input were fixed at 50% (w/w) and 54 kJ (900 W for 1 min), respectively,
      and amounted to 5.5 and 10.9 kJ to produce 1g of glucose after enzymatic
      hydrolysis and 1g ethanol after fermentation, respectively. In general, 1g
      ethanol can produce about 30 kJ of energy, and therefore, the energy input for
      the pretreatment was only 35% of the energy output. The approach developed in
      this study resulted in 92.9% higher energy savings for producing 1g ethanol when
      compared with the results of microwave pretreatments previously reported.

PMID- 21742489
TI  - Enhanced production of ganoderic acids in static liquid culture of Ganoderma
      lucidum under nitrogen-limiting conditions.
AB  - The effect of nitrogen limitation on the production of the antitumor compounds,
      ganoderic acids (GAs), by Ganoderma lucidum and on transcription levels of
      triterpene biosynthesis genes in this mushroom was investigated. At 3mM
      glutamine, a maximal content of GA-Mk, GA-T, GA-S, and GA-Me was 2.16, 11.76,
      31.09, and 7.04 MUg/mg cell dry weight, respectively, which was 2.8-, 5.8-, 8.3-,
      and 5.1-fold that obtained at 60mM glutamine. The transcription levels of
      biosynthetic genes encoding 3-hydroxy-3-methylglutaryl-CoA reductase, farnesyl
      pyrophosphate synthase, squalene synthase, lanosterol synthase, and a putative
      nitrogen regulator, AreA, were up-regulated by 37-, 18-, 4.5-, 3.2-, and 13-fold,
      respectively, in nitrogen limitation conditions, suggesting that increased GAs
      biosynthesis may result from higher expression of those genes. This study
      demonstrated a useful strategy for enhancing GAs production and provided useful
      information for further investigation on its biosynthesis regulation.

PMID- 21742490
TI  - Benzothiazole-based N-(phenylsulfonyl)amides as a novel family of PPARalpha
      antagonists.
AB  - The discovery of PPAR antagonists is emerging as an useful tool for elucidating
      the biological role of the receptor. Here we report the identification of N
      (phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of
      potent PPARalpha antagonists obtained from chemical modification of carboxylic
      acid agonists. In this work, a group of phenylsulfonamides were synthesized and
      in vitro evaluated against the agonistic effect of GW7647; they showed an
      inhibitory effect on PPARalpha activation, with best compounds revealing a dose
      dependent antagonistic profile. Some of these antagonists showed also an
      inhibitory effect on CPT1A pattern expression.

PMID- 21742491
TI  - Carbonic anhydrase I and II activation with mono- and dihalogenated histamine
      derivatives.
AB  - Mono- and dihalogenated histamine derivatives incorporating fluorine, chlorine
      and bromine have been prepared together with the corresponding boc-protected
      compounds at the aminoethyl group. They have been investigated as activators of
      the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The cytosolic human (h)
      isoforms hCA I and II were moderately activated by the boc-protected halogenated
      histamines and very effectively activated by the deprotected ones. Low nanomolar
      and subnanomolar hCA I and II activators have been detected for the first time,
      starting from histamine as lead which has an affinity of 2 MUM against isoform I
      and of 125 MUM against hCA II.

PMID- 21742492
TI  - Peptoid ligands that bind selectively to phosphoproteins.
AB  - Synthetic equivalents of phosphoprotein-specific antibodies would be valuable
      reagents for biological research, since these antibodies can often be difficult
      to produce. Protein phosphorylation is thought to result in significant
      conformational changes in most substrate proteins. Therefore, one approach might
      be to simply screen combinatorial libraries for ligands to the phosphorylated
      state in the hope of isolating a ligand that binds to a pocket created by the
      conformational shift. In this study, we probe this strategy by screening a
      peptoid library for ligands to the phosphorylated form of the Brd4 chromatin
      adaptor and transcriptional coactivator protein. We find that peptoids with high
      selectivity for binding to the phosphorylation form of Brd4 can indeed be
      isolated in this screen. Moreover, these ligands do not bind promiscuously to
      other phospho-proteins. However, attempts to employ these reagents as antibody
      substitutes in an immunoaffinity purification-like application showed that they
      do not perform as well as bona fide antibodies and that significant optimization
      will be required. This study highlights the potential and current limitations of
      a naive library screening strategy for phosphoprotein-specific antibody
      surrogates.

PMID- 21742493
TI  - Discovery of indazoles as inhibitors of Tpl2 kinase.
AB  - Synthesis, modeling and structure-activity relationship of indazoles as
      inhibitors of Tpl2 kinase are described. From a high throughput screening effort,
      we identified an indazole hit compound 5 that has a single digit micromolar Tpl2
      activity. Through SAR modifications at the C3 and C5 positions of the indazole,
      we discovered compound 31 with good potency in LANCE assay and cell-based p-Erk
      assay.

PMID- 21742494
TI  - Structure-activity relationship and docking studies of thiazolidinedione-type
      compounds with monoamine oxidase B.
AB  - The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP
      parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type
      compounds for monoamine oxidase A and B inhibition activity. These compounds were
      able to inhibit MAO-B over several log units of magnitude (82 nM to 600 MUM).
      Initial structure-activity relationship studies identified key areas to modify
      the aromatic substituted TZD compounds. Primarily, substitutions on the aromatic
      group and the TZD nitrogen were key areas where activity was enhanced within this
      group of compounds.

PMID- 21742495
TI  - Pyridine-derived gamma-secretase modulators.
AB  - SAR of a novel series of pyridine-derived gamma-secretase modulators is
      described. Compound 5 was found to be a potent modulator in vitro, which on
      further profiling, was found to decrease Abeta42 and Abeta40, and maintain (or
      increase) the levels of total Abeta. Furthermore, representative compounds 1 and
      5 demonstrated in vivo efficacy to lower Abeta42 in the brain without altering
      Notch processing in the peripheral.

PMID- 21742496
TI  - The design, synthesis and structure-activity relationships of novel isoindoline
      based histone deacetylase inhibitors.
AB  - The design, synthesis and biological evaluation of a novel series of isoindoline
      based hydroxamates is described. Several analogs were shown to inhibit HDAC1 with
      IC(50) values in the low nanomolar range and inhibit cellular proliferation of
      HCT116 human colon cancer cells in the sub-micromolar range. The cellular potency
      of compound 17e was found to have greater in vitro anti-proliferative activity
      than several compounds in late stage clinical trials for the treatment of cancer.
      The in vitro safety profiles of selected compounds were assessed and shown to be
      suitable for further lead optimization.

PMID- 21742497
TI  - Two cases of oculopharyngeal muscular dystrophy (OPMD) with the rare PABPN1
      c.35G>C; p.Gly12Ala point mutation.
AB  - Oculopharyngeal muscular dystrophy is a neuromuscular disease usually presenting
      in the 5th or 6th decades of life with a dominant inheritance pattern. In almost
      all cases the cause of the disease is the expansion of a DNA repeat sequence
      containing GCG and GCA codons in exon 1 of the PABPN1 gene from 10 to between 12
      and 17 repeats. However one case has been previously reported without the gene
      expansion but instead with a c.35G>C missense mutation converting a glycine codon
      to an alanine and resulting in a sequence of 13 contiguous alanine codons, thus
      mimicking the effect of the common expansion mutation. Here we report two further
      cases of OPMD caused by the c.35G>C point mutation. Clinical and pedigree data
      indicate the usual OPMD dominant inheritance pattern.

PMID- 21742498
TI  - Metronomic cyclophosphamide and methotrexate for breast cancer: enhanced efficacy
      by adding dalteparin and low-dose prednisone?

PMID- 21742499
TI  - Validity study of the standing test for imbalance and disequilibrium (SIDE): Is
      the amount of body sway in adopted postures consistent with item order?
AB  - The standing test for imbalance and disequilibrium (SIDE) is a discriminative
      measure developed for the purpose of identifying balance deficits that may cause
      falls. The purpose of the present study was to determine the validity of the
      sequence of postures used in SIDE. Subjects comprised 30 men with a mean (+/
      standard deviation) age of 21.9+/-3.11 years (range 19-32 years) and 30 women
      with a mean age of 20.7+/-1.24 years (range 19-23 years). Center of pressure
      (COP) was measured using a stabilometer recording for 30s with a 20-Hz sampling
      frequency. The measurement postures that were similar to postures adopted in the
      SIDE were: standing with feet 20cm apart; standing with legs close and the
      insides of both feet touching; two tandem standing positions (with the dominant
      foot forward and with the non-dominant foot forward); and two single-leg standing
      positions (on the dominant foot and on the non-dominant foot). We calculated
      total path length and envelopment area of sway from the COP data. Statistical
      differences in means were determined using the Tukey-Kramer multiple comparison
      test. Results indicate that the orders of total path length and envelopment areas
      of sway in each posture were consistent with the item order of SIDE. Significant
      differences existed between the means of total path length and envelopment areas
      of sway in each posture (p<0.05), with the exception of both tandem standing
      positions and both one-leg standing positions. The item order of SIDE appears to
      show concurrent validity in terms of the amount of body sway in the adopted
      postures.

PMID- 21742500
TI  - Alterations in systemic complement component 3a and 5a levels in patients with
      cerebral arteriovenous malformations.
AB  - The role of the complement cascade in the pathophysiology of cerebral
      arteriovenous malformation (AVM) is largely undefined. Complement subcomponents,
      C3a and C5a, are potent anaphylatoxins and key mediators of immuno-inflammatory
      response. Complement activation may contribute to the pro-inflammatory state
      observed in AVM. Thus, we sought to determine the systemic levels of C3a and C5a
      and their response to treatments in patients with AVM. Blood samples of 18
      patients undergoing treatment for unruptured AVM, and from 30 healthy control
      participants, were obtained at four times: (i) pre-treatment, (ii) 24-hours post
      embolization, (iii) 24-hours post-resection, and at 1-month follow-up. Plasma
      concentrations of C3a and C5a were measured using enzyme-linked immunosorbent
      assay. The pre-treatment mean plasma C3a level was significantly higher in
      patients with AVM (1817+/-168 ng/mL) compared to controls (1126+/-151 ng/mL). The
      mean C3a level decreased 24-hours after embolization (1482+/-170 ng/mL) and
      remained at statistically similar levels 24-hours after resection (1511+/-149
      ng/mL) and at 1-month follow-up (1535+/-133 ng/mL). Mean C3a levels at the three
      time points were higher than control levels.The baseline mean plasma C5a level
      was significantly elevated in patients with AVM (13.1+/-2.2 ng/mL) compared to
      controls (3.9+/-1.5 ng/mL).Mean C5a level decreasedpost-embolization (8.2+/-2.3
      ng/mL) and remained at similar levels post-resection (8.5+/-3.0 ng/mL) and at 1
      month follow-up (7.7+/-2.9 ng/mL). Mean C5a levels at the three time points were
      significantly higher than the control levels. We conclude that systemic C3a and
      C5a levels in patients with AVM are elevated at baseline, decrease significantly
      after embolization, and remain at the new baseline levels after surgery and 1
      month follow-up.

PMID- 21742501
TI  - Exophytic ependymoma of the thoracic spine.
AB  - Exophytic ependymomas of the spinal cord are very rare outside the filum or conus
      region. We present a patient with a thoracic spinal cord intradural
      extramedullary and intramedullary, World Health Organization grade II ependymoma.
      Gross total resection of the extramedullary component with subtotal resection of
      the intramedullary tumor was achieved, since there was no clear distinction
      between cord and tumor. The patient received postoperative external beam
      radiotherapy for residual tumor, and at a 2-year follow-up he is ambulatory
      without evidence of tumor recurrence.

PMID- 21742502
TI  - Contraversive shift of conjugate eye deviation in hemispheric stroke indicates
      emerging mass effect.
AB  - Conjugate eye deviation (CED) towards the ipsilateral or the contralateral side
      of the brain lesion can occur as a result of acute hemispheric stroke. To our
      knowledge, there have been no reports of CED shifting from the lesional side to
      the contralateral side in acute hemispheric stroke in the literature. We present
      four patients with right hemispheric stroke with a forced CED shift from the
      right to the left side during the acute stage with corresponding mass effect on
      the right internal capsule and right thalamus, as shown on brain imaging. Mass
      effect on thalamic mediated circuits and the corticopontine projection within the
      internal capsule probably underlies this CED shift via the dynamic balance of
      oculomotor control between the two hemispheres. Contraversive CED shift is a
      potentially useful early predictor of emerging mass effect in acute hemispheric
      stroke.

PMID- 21742503
TI  - Clinical characteristics and diagnostic imaging of epidermoid tumors.
AB  - Epidermoid tumors are rare, benign congenital lesions which typically present
      between the third and fifth decades of life. They are thought to originate from
      ectodermal cells misplaced during neural tube formation and separation. While
      epidermoids may present anywhere in the cranial vault, they are
      characteristically located intradurally and in a paramedian position within the
      cerebellopontine angle and parasellar regions. Although imaging results may vary
      depending upon cystic content, CT scanning generally reveals a well
      circumscribed, nonenhancing, lobulated, hypodense mass. They are hypointense on
      T1-weighted MRI, and hyperintense on T2-weighted MRI, diffusion-weighted imaging
      and fluid-attenuated inversion recovery sequences. The use of appropriate
      neuroimaging should be utilized to differentiate epidermoids from other
      intracranial lesions. While gross total resection of these tumors is the
      definitive treatment to prevent recurrence and aseptic meningitis, a subtotal
      resection may be necessary to preserve neurological function.

PMID- 21742504
TI  - Internal carotid artery dissection and stroke associated with wakeboarding.
AB  - Wakeboarding is a popular water sport but has significant potential for trauma
      due to the high velocities, rotational maneuvers, acceleratory forces, water
      obstacles, and general lack of protective equipment used. Head or neck trauma is
      a concern, which may be even more common with wakeboarding than other water
      sports, but the true trauma incidence is unknown and probably underreported.
      While traumatic brain injury has been reported to occur during wakeboarding we
      present an unusual mechanism of central nervous system injury in which a young
      adult male developed a carotid artery dissection and stroke shortly following a
      wakeboarding accident.

PMID- 21742505
TI  - Cerebral edema and a transtentorial brain herniation syndrome associated with
      pandemic swine influenza A (H1N1) virus infection.
AB  - Acute encephalitis, encephalopathy, and seizures are known rare neurologic
      sequelae of respiratory tract infection with seasonal influenza A and B virus,
      but the neurological complications of the pandemic 2009 swine influenza A (H1N1)
      virus, particularly in adults, are ill-defined. We document two young adults
      suffering from H1N1-associated acute respiratory distress syndrome and renal
      failure who developed cerebral edema. The patients acutely developed a
      transtentorial brain herniation syndrome including a unilateral third nerve palsy
      (dilated and unresponsive pupils), elevated intracranial pressure, coma, and
      radiological evidence of diffuse cerebral edema. In both patients, neurological
      deterioration occurred in the context of hyponatremia and a systemic inflammatory
      state. These patients illustrate that severe neurologic complications, including
      malignant cerebral edema, can occur in adults infected with H1N1 virus, and
      illustrate the need for close neurological monitoring of potential neurological
      morbidities in future pandemics.

PMID- 21742506
TI  - Discovery of vinylogous carbamates as a novel class of beta-ketoacyl-acyl carrier
      protein synthase III (FabH) inhibitors.
AB  - beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step
      of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria.
      The important role of this essential enzyme combined with its unique structural
      features and ubiquitous occurrence in bacteria has made it an attractive new
      target for the development of new FabH inhibitors. We first used a structure
      based approach to develop 24 new vinylogous carbamates (4a-15a, 4b-15b) that
      target FabH for the development of new antibiotics in this paper. Potent FabH
      inhibitory and selective anti- Gram-negative bacteria activities were observed in
      most of these vinylogous carbamates. Especially, compound 6a and 7a showed the
      most potent FabH inhibitory activity with IC50 of 2.6 and 3.3 MUM, respectively.
      Docking simulation was performed to position compound 6a into the Escherichia
      coli FabH active site and the possible binding conformation of compounds has been
      proposed. The biological data and molecular docking indicated that compounds 6a
      and 7a were potent inhibitors of E. coli FabH as antibiotics deserving further
      research.

PMID- 21742507
TI  - Construction of dopamine sensors by using fluorescent ribonucleopeptide
      complexes.
AB  - A facile strategy of stepwise molding of a ribonucleopeptide (RNP) complex
      affords fluorescent RNP sensors with selective dopamine recognition. In vitro
      selection of a RNA-derived RNP library, a complex of the Rev peptide and its
      binding site Rev Responsive Element (RRE) RNA appended with random nucleotides in
      variable lengths, afforded RNP receptors specific for dopamine. The modular
      structure of the RNP receptor enables conversion of dopamine-binding RNP
      receptors to fluorescent dopamine sensors. Application of conditional selection
      schemes, such as the variation of salt concentrations and application of a
      counter-selection step by using a competitor ligand norepinephrine resulted in
      isolation of RNP receptors with defined dopamine-binding characteristics.
      Increasing the salt condition at the in vitro selection stage afforded RNP
      receptors with higher dopamine affinity, while addition of norepinephrine in the
      in vitro selection milieu at the counter-selection step reinforced the
      selectivity of RNP receptors to dopamine against norepinephrine. Thermodynamic
      analyses and circular dichroismic studies of the dopamine-RNP complexes suggest
      that the dopamine-binding RNP with higher selectivity against norepinephrine
      forms a pre-organized binding pocket and that the dopamine-binding RNP with
      higher affinity binds dopamine through the induced-fit mechanism. These results
      indicate that the selection condition controls the ligand-binding mechanism of
      RNP receptors.

PMID- 21742508
TI  - Probing the in vivo biosynthesis of scytonemin, a cyanobacterial ultraviolet
      radiation sunscreen, through small scale stable isotope incubation studies and
      MALDI-TOF mass spectrometry.
AB  - Scytonemin is a dimeric indole phenolic pigment found in the sheaths of many
      cyanobacteria. This pigment absorbs UV radiation protecting subtending
      cyanobacterial cells from harmful effects. Based on scytonemin's unique chemical
      structure, the pathway to its biosynthesis is uncertain, thus motivating the
      current investigation. Herein, we report the incorporation of both tyrosine and
      tryptophan into scytonemin, and provide in vivo data supporting the tryptophan
      origin of the ketone carbon involved in the condensation of the two biosynthetic
      precursors. This study also reports on the new use of a small-scale, MALDI-TOF
      mass spectrometry technique to monitor the incorporation of isotopically labeled
      tyrosine during scytonemin biosynthesis.

PMID- 21742509
TI  - A comprehensive review of radon emanation measurements for mineral, rock, soil,
      mill tailing and fly ash.
AB  - To our knowledge, this paper is the most comprehensive review to cover most
      studies, published in the past three decades at least, of radon emanation
      measurements. The radon emanation fraction, a possibility of radon atoms
      generated in a material escaping from its grains, has been widely measured for a
      variety of materials. The aim of this review is to organize a huge number of such
      data accumulated. The representative values of the emanation fraction for
      minerals, rocks, soils, mill tailings and fly ashes were derived to be 0.03,
      0.13, 0.20, 0.17 and 0.03, respectively. Current knowledge of the emanation
      processes was also summarized to discuss their affected factors.

PMID- 21742510
TI  - Automated quantitative analysis of in-situ NaI measured spectra in the marine
      environment using a wavelet-based smoothing technique.
AB  - An algorithm for automated analysis of in-situ NaI gamma-ray spectra in the
      marine environment is presented. A standard wavelet denoising technique is
      implemented for obtaining a smoothed spectrum, while the stability of the energy
      spectrum is achieved by taking advantage of the permanent presence of two energy
      lines in the marine environment. The automated analysis provides peak detection,
      net area calculation, energy autocalibration, radionuclide identification and
      activity calculation. The results of the algorithm performance, presented for two
      different cases, show that analysis of short-term spectra with poor statistical
      information is considerably improved and that incorporation of further
      advancements could allow the use of the algorithm in early-warning marine
      radioactivity systems.

PMID- 21742511
TI  - Modified internal mandibular distraction osteogenesis in the treatment of
      micrognathia secondary to temporomandibular joint ankylosis: 4-year follow-up of
      a case.
AB  - Micrognathia and obstructive sleep apnoea syndrome (OSAS) are problems subsequent
      to temporomandibular joint ankylosis (TMJa) in growing patients. For patients
      with micrognathia and OSAS secondary to TMJa, it is important to restore proper
      mandibular form and dimension, achieve occlusal stability and recover
      satisfactory joint movement. We report a 4-year follow-up of a patient with
      micrognathia and OSAS secondary to bilateral TMJa. The treatment of this patient
      involved (1) a modified internal mandibular distraction osteogenesis without
      altering the pre-existing occlusion; (2) TMJ arthroplasty in which the dislocated
      disc was found and repositioned and the shape of the glenoid fossa and articular
      head was formed without removing bone in vertical dimension; (3) passive mouth
      opening exercise with an individualized occlusal pad postoperatively for one
      month; and (4) orthodontic treatment for the occlusal disturbance and active
      mouth-opening exercise for one year. After the treatment the micrognathia was
      corrected; the oropharyngeal airway was increased significantly; mouth-opening
      increased to 40mm intraoperatively was maintained at 36.66mm 4 years after
      surgery. Satisfactory occlusion was achieved after orthodontic treatment. Through
      the 4-year follow-up, no signs of reankylosis were found. In conclusion, this new
      clinical protocol is a safe, effective and quick way to treat micrognathia and
      OSAS secondary to TMJa.

PMID- 21742512
TI  - Apelin, vaspin, visfatin and adiponectin in large for gestational age infants
      with insulin resistance.
AB  - OBJECTIVE: To investigate the relation of circulating four adipokines (apelin,
      vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for
      gestational age (LGA) infants. PATIENTS AND METHODS: Forty LGA infants (20 LGA
      born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34
      appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and
      insulin resistance was evaluated using the homeostasis model assessment (HOMA
      IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity
      check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels
      were determined by radioimmunoassay. Determination of visfatin and apelin levels
      was performed by enzyme immunoassay. RESULTS: HOMA-IR, apelin and visfatin levels
      (p<0.001, p<0.001, p<0.001, respectively) were significantly elevated and
      adiponectin levels, FGIR and QUICK-I values. (p<0.001, p<0.001, p<0.05,
      respectively) were significantly lower in the LGA group. Vaspin levels were
      higher in the LGA group than AGA neonates without a significance. The LGA infants
      with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values,
      fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values.
      Apelin and visfatin were correlated positively, and adiponectin was correlated
      negatively with birthweight, HOMA-IR values and fasting insulin levels.
      CONCLUSION: Based on the findings of this study, it is too difficult to explain
      relation between birthweight and these adipocytokines, but findings of high
      insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates
      showed that these adipocytokines can be used as a good predictor for metabolic
      syndrome.

PMID- 21742513
TI  - Autocrine production of interleukin-8 confers cisplatin and paclitaxel resistance
      in ovarian cancer cells.
AB  - It has been widely reported that interleukin-8 (IL-8) is overexpressed in ovarian
      cyst fluid, ascites, serum, and tumor tissue from ovarian cancer (OVCA) patients,
      and elevated IL-8 expression correlates with a poor final outcome and
      chemosensitivity. However, the role of IL-8 expression in the acquisition of the
      chemoresistance phenotype and the underlining mechanisms of drug resistance in
      OVCA cells are not yet fully understood. Here we show that both exogenous (a
      relatively short period of treatment with recombination IL-8) and endogenous IL-8
      (by transfecting with plasmid encoding for sense IL-8) induce cisplatin and
      paclitaxel resistance in non-IL-8-expressing A2780 cells, while deleting of
      endogenous IL-8 expression in IL-8-overexpressing SKOV-3 cells (by transfecting
      with plasmid encoding for antisense IL-8) promotes the sensitivity of these cells
      to anticancer drugs. IL-8-mediated resistance of OVCA cells exhibits decreased
      proteolytic activation of caspase-3. Meanwhile, the further study demonstrates
      that the chemoresistance caused by IL-8 is associated with increased expression
      of both multidrug resistance-related genes (MDR1) and apoptosis inhibitory
      proteins (Bcl-2, Bcl-xL, and XIAP), as well as activation of PI3K/Akt and
      Ras/MEK/ERK signaling. Therefore, modulation of IL-8 expression or its related
      signaling pathway may be a promising strategy of treatment for drug-resistant
      OVCA.

PMID- 21742514
TI  - Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic
      blood pressure in patients suffering from relapsing or refractory lupus
      nephritis: a randomized and placebo-controlled study.
AB  - OBJECTIVE: Despite highly expensive treatments, lupus nephritis remains a major
      cause of morbidity and mortality in patients with relapsing or refractory lupus
      nephritis. Meanwhile, experimental studies indicate that curcumin attenuates both
      the binding of autoantibodies from systemic lupus erythematosus patients to their
      cognate antigens and also the inflammatory responses of tumor necrosis factor
      alpha-stimulated human endothelial cells. Therefore, in this study we
      investigated effect(s) of oral curcumin supplementation on patients suffering
      from relapsing or refractory lupus nephritis. DESIGN: A randomized and placebo
      controlled study was carried out. SETTING: The present study was conducted in
      Lupus clinic of Hafez Hospital, Out-Patient Department of Shiraz University of
      Medical Sciences. PATIENTS: A total of 24 patients with relapsing or refractory
      biopsy-proven lupus nephritis, who were randomized in 2 groups (trial [n = 12]
      and control [n = 12] groups) were included in this study. INTERVENTION: With each
      meal, each patient in the trial group received 1 capsule for 3 months, which
      contained 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (3
      capsules daily). The control group received 3 capsules (1 with each meal) for the
      same period, which contained starch and were identical in color and size to
      capsules given to patients in the trial group. MAIN AUTOMATIC MEASURE: Data were
      analyzed using Statistical Package for the Social Sciences software version 15.0.
      RESULTS: A significant decrease in proteinuria was found when comparing pre-
      (954.2 +/- 836.6) and 1, 2, and 3 months supplementation values (448.8 +/- 633.5,
      235.9 +/- 290.1, and 260.9 +/- 106.2, respectively) in the trial group. Also,
      systolic blood pressure and hematuria were found to decrease significantly when
      pre- and post-turmeric supplementation values were compared in the trial group.
      However, placebo capsules did not exert any statistically significant effect on
      measured variables in the control group over 3 months of the study. No adverse
      effect related to turmeric supplementation was observed during the trial.
      CONCLUSION: Short-term turmeric supplementation can decrease proteinuria,
      hematuria, and systolic blood pressure in patients suffering from relapsing or
      refractory lupus nephritis and can be used as an adjuvant safe therapy for such
      patients.

PMID- 21742515
TI  - Association between fish consumption and nephropathy in American Indians--the
      Strong Heart Study.
AB  - OBJECTIVE: The present study examined the association between fish consumption
      and nephropathy in American Indians. METHODS: In the family cohort of the Strong
      Heart Study, we investigated 2,261 participants with baseline examination between
      2001 and 2003 and follow-up examination between 2006 and 2008. The average follow
      up period was 5.4 years. We defined fish consumption as the sum of dietary intake
      of tuna, fried fish, and nonfried fish obtained from a validated food frequency
      questionnaire. Nephropathy was defined as microalbuminuria (urinary albumin
      creatinine ratio [ACR]: 30 to 299 mg/g), macroalbuminuria (urinary ACR: >= 300
      mg/g), or an estimated glomerular filtration rate of <60 mL/min/1.73 m(2). Using
      regression models, we examined the association between fish consumption measured
      at baseline and 2 outcomes in nephropathy present at follow-up, albuminuria, or
      renal impairment, and change in urinary ACR or estimated glomerular filtration
      rate between baseline and follow-up examinations. RESULTS: The prevalence of
      microalbuminuria, macroalbuminuria, and renal impairment was 13%, 3%, and 4%,
      respectively. The fish items consumed by the participants were predominantly deep
      fried. We found no associations between fish consumption and any measure of
      nephropathy after adjusting for demographic, clinical, lifestyle, and dietary
      factors. CONCLUSIONS: Dietary intake of predominantly fried fish was not
      associated with a lower risk of nephropathy in American Indians.

PMID- 21742516
TI  - Normal body scheme and absent phantom limb experience in amputees while dreaming.
AB  - While dreaming amputees often experience a normal body image and the phantom limb
      may not be present. However, dreaming experiences in amputees have mainly been
      collected by questionnaires. We analysed the dream reports of amputated patients
      with phantom limb collected after awakening from REM sleep during overnight
      videopolysomnography (VPSG). Six amputated patients underwent overnight VPSG
      study. Patients were awakened during REM sleep and asked to report their dreams.
      Three patients were able to deliver an account of a dream. In all dreaming
      recalls, patients reported that the amputated limbs were intact and completely
      functional and they no longer experienced phantom limb sensations. Phantom limb
      experiences, that during wake result from a conflict between a pre-existing body
      scheme and the sensory information on the missing limb, were suppressed during
      sleep in our patients in favour of the image of an intact body accessed during
      dream.

PMID- 21742517
TI  - The benefits of comparative audit in vascular surgery.

PMID- 21742518
TI  - Comments regarding 'Increased circulating levels of basement-membrane components
      in patients with abdominal aortic aneurysms--a pilot study'.

PMID- 21742519
TI  - Thrombolytic along with anti-platelet activity of crinumin, a protein constituent
      of Crinum asiaticum.
AB  - Several anticoagulants, anti-platelet and thrombolytic medications are used for
      the treatment of thrombotic disorders. Anti-coagulants and anti-platelet agents
      prevent the formation of blood clots but do not dissolve existing clots, whereas
      thrombolytic agents are able to dissolve a clot but emboli can form even after
      successful treatment. Thus, none of them provide a permanent and complete
      solution. In this regard a single molecule that could both dissolve the clot and
      prevent the formation of new clots would be useful in the treatment of thrombotic
      diseases. Crinumin, a stable and active (in many adverse conditions) serine
      protease, shows plasmin-like fibrinolytic activity and inhibits platelet
      aggregation and P-selectin exposure, as established by photography, phase
      contrast microscopy, whole blood optical Lumi-aggregometry and flow cytometry.
      Crinumin could be an efficient and inexpensive therapeutic agent for the
      treatment and prevention of thromboembolic diseases.

PMID- 21742520
TI  - Response to the documentary Pedigree Dogs Exposed: three reports and their
      recommendations.
AB  - The BBC documentary Pedigree Dogs Exposed precipitated three inquiries into dog
      breeding and showing in the UK. Recommendations arising from the inquiries have
      been and are being implemented. The organisation that was most criticised in the
      documentary, the Kennel Club, responded quickly to address the major issues and
      has, for the most part, embraced the inquiries' recommendations. When the
      recommendations are fully implemented, there will have been some major changes in
      dog breeding and showing, with a far stronger emphasis placed on health and
      welfare of dogs.

PMID- 21742521
TI  - Getting priorities straight: risk assessment and decision-making in the
      improvement of inherited disorders in pedigree dogs.
AB  - The issue of inherited disorders in pedigree dogs is not a recent phenomenon and
      reports of suspected genetic defects associated with breeding practices date back
      to Charles Darwin's time. In recent years, much information on the array of
      inherited defects has been assimilated and the true extent of the problem has
      come to light. Historically, the direction of research funding in the field of
      canine genetic disease has been largely influenced by the potential
      transferability of findings to human medicine, economic benefit and importance of
      dogs for working purposes. More recently, the argument for a more canine welfare
      orientated approach has been made, targeting research efforts at the alleviation
      of the most suffering in the greatest number of animals. A method of welfare risk
      assessment was initially developed as a means of objectively comparing, and thus
      setting priorities for, different welfare problems. The method has been applied
      to inherited disorders in pedigree dogs to investigate which disorders have the
      greatest welfare impact and which breeds are most affected. Work in this field
      has identified 396 inherited disorders in the top 50 most popular breeds in the
      UK. This article discusses how the results of welfare risk assessment for
      inherited disorders can be used to develop strategies for improving the health
      and welfare of dogs in the long term. A new risk assessment criterion, the Breed
      Disorder Welfare Impact Score (BDWIS), which takes into account the proportion of
      life affected by a disorder, is introduced. A set of health and welfare goals is
      proposed and strategies for achieving these goals are highlighted, along with
      potential rate-determining factors at each step.

PMID- 21742522
TI  - The Advisory Council on the Welfare Issues of Dog Breeding.
AB  - This paper summarises the factors that led to the formation of the Advisory
      Council on the Welfare Issues of Dog Breeding and sets out some of the challenges
      facing the Council. Common to all types of dog is the irresponsible way in which
      they can be produced, purchased and owned, and the considerable welfare problems
      that may arise as a direct consequence of these actions. In pedigree and purebred
      dogs, specific welfare problems may also be the result of the manner in which
      some of them are bred, as well as a variety of breed-related and inherited
      disorders and a number of other complex issues. These include the breeding
      strategies adopted, including cross-breeding for so-called 'designer dog'
      hybrids, and the influence of showing and judging on the production of over
      exaggerated conformational features. The Advisory Council's science-based
      collaborative approach is key to tackling these issues.

PMID- 21742523
TI  - How the Kennel Club is tackling inherited disorders in the United Kingdom.
AB  - Health screening of potential canine breeding stock can provide invaluable
      information to allow breeders to select against inherited diseases in their
      breeding programmes. This review details the screening programmes that are
      currently available to UK dog breeders and evaluates their impact as selective
      tools for dog breeders.

PMID- 21742524
TI  - The association between indicators of inflammation and liver variables during the
      transition period in high-yielding dairy cows: an observational study.
AB  - During the transition period, cows are confronted with infectious and
      inflammatory challenges leading to an acute phase response (APR) marked by
      increased hepatic synthesis of positive acute phase reactants (+AP) and a
      decrease in negative acute phase reactants (-AP). The aim of this study was to
      quantify the APR in 21 high-yielding dairy cows studied from 9 days before until
      42 days after calving, and to assess the association between the APR, disease
      incidence and indicators of liver function. Repeated blood samples were analyzed
      for -AP (retinol, albumin, cholesterol), +AP (haptoglobin, caeruloplasmin),
      paraoxonase, and liver-associated variables (aspartate aminotransferase, gamma
      glutamyl transferase, bilirubin). All cows displayed postpartum decreases in -AP
      and paraoxonase, and increases in +AP and liver variables. When retrospectively
      categorized, cows presenting a stronger -AP decline displayed higher +AP and
      liver variables, and a higher disease incidence compared to cows with a milder
      decline. Altogether, typical changes in -AP and +AP identify the transition
      period as a time of increased inflammatory load. Group differences in liver
      variables suggest that a more severe APR may be associated with altered liver
      function. However, no causal relationship can be proven based on this
      observational dataset, and results should be interpreted cautiously.

PMID- 21742525
TI  - Relaxation times of spin states of all ranks and orders of quadrupolar nuclei
      estimated from NMR z-spectra: Markov chain Monte Carlo analysis applied to 7Li+
      and 23Na+ in stretched hydrogels.
AB  - The NMR z-spectra of 7Li+ and 23Na+ in stretched hydrogels contain five minima,
      or critical values, with a sharp "dagger" on the central dip. The mathematical
      representation of such z-spectra from spin-3/2 nuclei contains nine distinct (the
      total is 15 but there is redundancy of the +/-order-numbers) relaxation rate
      constants that are unique for each of the spin states, up to rank 3, order 3. We
      present an approach to multiple-parameter-value estimation that exploits the high
      level of separability of the effects of each of the relaxation rate constants on
      the features of the z-spectrum. The Markov chain Monte Carlo (MCMC) method is
      computationally demanding but it yielded statistically robust estimates (low
      coefficients of variation) of the parameter values. We describe the
      implementation of the MCMC analysis (in the present context) and posit that it
      can obviate the need for using multiple-quantum filtered RF-pulse sequences to
      estimate all relaxation rate constants/times under experimentally favorable, but
      readily achievable, circumstances.

PMID- 21742526
TI  - Experimental evidence of oxidative stress in plasma of homocystinuric patients: a
      possible role for homocysteine.
AB  - Homocystinuria is an inherited disorder biochemically characterized by high
      urinary excretion of homocystine and increased levels of homocysteine (Hcy) and
      methionine in biological fluids. Affected patients usually have a variety of
      clinical and pathologic manifestations. Previous experimental data have shown a
      relationship between Hcy and oxidative stress, although very little was reported
      on this process in patients with homocystinuria. Therefore, in the present study
      we evaluated parameters of oxidative stress, namely carbonyl formation,
      malondialdehyde (MDA) levels, sulfhydryl content and total antioxidant status
      (TAS) in patients with homocystinuria at diagnosis and under treatment with a
      protein restricted diet supplemented by pyridoxine, folate, betaine, and vitamin
      B(12). We also correlated plasma Hcy and methionine concentrations with the
      oxidative stress parameters examined. We found a significant increase of MDA
      levels and carbonyl formation, as well as a reduction of sulfhydryl groups and
      TAS in plasma of homocystinuric patients at diagnosis relatively to healthy
      individuals (controls). We also verified that Hcy levels were negatively
      correlated with sulfhydryl content and positively with MDA levels. Furthermore,
      patients under treatment presented a significant reduction of the content of MDA,
      Hcy and methionine concentrations relatively to patients at diagnosis. Taken
      together, the present data indicate that lipid and protein oxidative damages are
      increased and the antioxidant defenses diminished in plasma of homocystinuric
      patients, probably due to increased reactive species elicited by Hcy. It is
      therefore presumed that oxidative stress participates at least in part in the
      pathogenesis of homocystinuria.

PMID- 21742527
TI  - Aggregation of alpha-synuclein in brain samples from subjects with
      glucocerebrosidase mutations.
AB  - Recent studies show an increased frequency of mutations in the glucocerebrosidase
      gene (GBA1) in patients with alpha-synucleinopathies including Parkinson disease.
      Some patients with Gaucher disease (GD) develop parkinsonism with alpha-synuclein
      positive inclusions post mortem. Proteins were extracted from the cerebral cortex
      of subjects with synucleinopathies with and without GBA1 mutations, controls and
      patients with GD. Patients with GBA1-associated synucleinopathies showed
      aggregation of oligomeric forms of alpha-synuclein in the SDS-soluble fraction,
      while only monomeric forms of alpha-synuclein were seen in subjects with GBA1
      mutations without parkinsonism. Thus, brains from patients with GBA1-associated
      parkinsonism show biochemical characteristics typical of Lewy body disorders.

PMID- 21742528
TI  - RNA expressions of AHR, ARNT and CYP1B1 are influenced by AHR Arg554Lys
      polymorphism.
AB  - AIM: The aryl hydrocarbon receptor (AHR) is a ligand activated transcription
      factor that together with Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT)
      controls the expression of Xenobiotic metabolising enzymes (XME) such as CYP1B1.
      In the absence of exogenous ligands, AHR is supposed to be involved in promotion
      of cell cycle progression. Polymorphisms of the AHR gene are suggested to be
      associated with susceptibility to cancer. Because of its critical role in
      xenobiotic induced toxicity and carcinogenesis as well as its ligand independent
      relevance we investigated the effects of AHR Arg554Lys Polymorphism on gene
      expression level of the AHR, ARNT and CYP1B1. METHODS: Detection of the AHR
      Arg554Lys polymorphism of the AHR gene was performed by rapid capillary PCR with
      melting curve analysis. The quantitative Real-Time PCR (qRT-PCR) of AHR, ARNT and
      CYP1B1 mRNAs was carried out in white blood cells from 287 Caucasians.
      Calculations of expression were made with the 2(-DeltaDeltaCT) method. RESULTS:
      The relative AHR mRNA expression revealed significant differences between the two
      homozygote AHR genotypes Arg554Arg (11.0+/-1.0; n=228) and Lys554Lys (0.6+/-0.4;
      n=3; p<0.001). Also significant differences were seen between the heterozygote
      genotype Arg554Lys (13.0+/-3.0; n=40) and the homozygote Lys554Lys genotype
      (0.6+/-0.4; n=3; p<0.001). These differences above were replicated significantly
      in the relative mRNA expression of ARNT and CYP1B1. Comparing the determined CT
      values, a correlation coefficient of R=0.748 for AHR and ARNT, R=0.626 for ARNT
      and CYP1B1 as well as R=0.533 for AHR and CYP1B1 was calculated. CONCLUSION: Our
      findings suggest that the homozygote variant genotype of AHR Lys554Lys is
      associated with a significantly lower AHR, ARNT and CYP1B1 mRNA expression.

PMID- 21742529
TI  - [Protocol for use of subcutaneous reservoir in a gynecological oncology unit].
AB  - Use of subcutaneous reservoir has been extended in recent years in response to
      the need of chronic intravenous treatments. Some cancer patients and need to have
      a venous access maintained. In them is not advisable to use a peripheral vein,
      the sclerosing effect and/or irritating on the endothelium have many of the drugs
      administered, and the numerous venous punctures to which are often subjected. In
      this regard, the establishment of a permanent subcutaneous reservoir at the
      central level can obtain blood samples and administer all types of intravenous
      therapies. Although it also has the advantage of a low incidence of infections,
      the possibility of outpatient use and well accepted by patients. The system
      consists of a silicone venous catheter that is placed below the subcutaneous
      tissue and provides a vascular access, easy to find, secure and durable. Despite
      its frequent use today, this technique is not completely without risk, and among
      the possible complications of infectious diseases, thrombosis, catheter
      migration, occlusion, pneumothorax or vascular erosion. The aim of this study was
      to describe the protocol using the subcutaneous reservoir held in the unit of
      gynecologic oncology, University Hospital Virgen de las Nieves in Granada.

PMID- 21742530
TI  - First report on sexually transmitted infections among trans (male to female
      transvestites, transsexuals, or transgender) and male sex workers in Argentina:
      high HIV, HPV, HBV, and syphilis prevalence.
AB  - OBJECTIVES: Due to the scarce data on the prevalence of sexually transmitted
      infections (STIs) among male-to-female trans-sex workers (TSW) and male sex
      workers (MSW) in Argentina, the present study aimed to estimate the incidence of
      human immunodeficiency virus (HIV), and the prevalence of HIV, hepatitis B virus
      (HBV), hepatitis C virus (HCV), and Treponema pallidum. Human papillomavirus
      (HPV) and Chlamydia trachomatis infections were tested among TSW. METHODS: Two
      hundred and seventy-three TSW and 114 MSW were recruited by nongovernmental
      organizations. HIV incidence was estimated by STARHS (serologic testing algorithm
      for recent HIV seroconversion). HPV and C. trachomatis infections were tested in
      anal cells from TSW. RESULTS: TSW showed significantly higher prevalences of HIV
      (34.1 vs. 11.4%), HBV (40.2 vs. 22.0%), and T. pallidum (50.4 vs. 20.4%) than
      MSW. TSW tested positive for HPV in 111/114 cases and for C. trachomatis in 4/80
      cases. Investigation of HBV, HCV, HIV, and T. pallidum co-infections showed that
      72% of TSW and 39% of MSW had at least one STI. T. pallidum was the most frequent
      mono-infection. The estimated HIV incidence was 10.7 per 100 person-years (95%
      confidence interval (CI) 3.8-17.7) for TSW and 2.3 per 100 person-years (95% CI 0
      6.7) for MSW. CONCLUSIONS: The high prevalence of STIs and the high incidence of
      HIV demonstrate the great vulnerability of these high-risk populations and
      indicate the urgent need for preventive strategies on intervention and
      facilitation of access to healthcare programs.

PMID- 21742531
TI  - Are the results of multiple drilling and alendronate for osteonecrosis of the
      femoral head better than those of multiple drilling? A pilot study.
AB  - OBJECTIVES: The treatment of osteonecrosis of the femoral head (ONFH) remains
      controversial. A recently proposed treatment is multiple drilling core
      decompression combined with systemic alendronate as a femoral head-preserving
      procedure for ONFH. However, it is not known whether alendronate enhances the
      risk of collapse. We wondered whether the combined procedure could delay or
      prevent progression of ONFH compared to multiple drilling alone. METHODS:
      Patients with early-stage ONFH were randomly assigned to be treated with either
      multiple drilling combined with alendronate (47 patients, 67 hips) or multiple
      drilling alone (46 patients, 60 hips). We defined failure as the need for THA or
      a Harris score less than 70. The minimum follow-up was 48 months for the 77
      patients completing the protocol. RESULTS: After a minimum 4-year follow-up, 91%
      (40/44) of patients with Stage II disease and 62% (8/13) of patients with Stage
      III disease had not required THA in alendronate group, compared to 79% (31/39) of
      patients with Stage II disease and 46% (6/13) of patients with Stage III disease
      had not required THA in control group (P=0.12, P=0.047, respectively). Small or
      medium and central lesions had a better successful rate in both groups. Risk
      factors did not seem to affect the clinical successful rate of this procedure.
      CONCLUSIONS: Multiple small-diameter drilling core decompression combined with
      systemic alendronate administration can reduce pain and delay progression of
      early-stage ONFH. Even in Ficat IIA and III hips, some benefit was obtained from
      this approach at least delay in the need for THA.

PMID- 21742532
TI  - The Hawthorne effect: stronger than the placebo effect?

PMID- 21742533
TI  - [Is it possible to prevent preterm births outside of level-3 maternity wards?
      Experience of Greater Lyon perinatal network].
AB  - OBJECTIVE: The main objective of this study was to calculate the percentage of
      preterm births before 28 weeks gestational age (weeks GA) outside level-3
      maternity wards and determine how many could have been prevented. METHODS: This
      was an observational, multicenter, retrospective cohort study, which included all
      the deliveries that occurred between 24 and 27 weeks GA + 6 days in the Greater
      Lyon perinatal network (France) occurring between first of March 2008 and first
      of March 2009. In utero transfers (IUTs) and newborn transfers (NBTs) which were
      carried out outside the network, medical abortions, and foetal deaths in utero
      were excluded. The duration between patient's arrival in the level 1 and 2
      maternity and birth was compared at the 97(th) percentile of the mother's
      transfer time in level-3 maternity. Births that occurred outside of level-3
      maternity wards were considered avoidable each time the first duration was more
      than the second. RESULTS: During the study period, 113 infants were born alive
      between 24 and 27 weeks GA+6 days in the network. They were all included in the
      study. Ninety were born in a level-3 maternity ward and 23 were born in level-1
      and 2 maternity wards (20%). There were 35 requests for IUT and 28 were carried
      out (80%). In 65% of non-level 3 births, no IUT was requested. In 17% of cases,
      an IUT request could have prevented births in level 1/2 maternity wards. If twin
      pregnancies had been transferred to a level-3 maternity ward, 26% of non-level 3
      births would have been avoided. If all high-risk pregnancies had been transferred
      to a level-3 maternity ward, 40% of non-level 3 births would have been avoided.
      DISCUSSION AND CONCLUSION: Any time a pregnant woman is hospitalized in a type
      1/2 maternity ward before 28 weeks GA, doctors should consider an in utero
      transfer to a level-3 maternity ward. It may be possible to lower the birth-rate
      of non-level 3 births by a targeted increase in in utero transfers and by
      transferring high-risk pregnancies to a level-3 maternity ward.

PMID- 21742534
TI  - [Emergencies in obstetrics: a passion?].

PMID- 21742535
TI  - [Early evaluation of the feasibility of robot-assisted laparoscopy in the
      surgical treatment of deep infiltrating endometriosis].
AB  - BACKGROUND: Preliminary study of the feasibility of robot-assisted laparoscopy
      for deep pelvic endometriosis nodule resection. PATIENTS AND METHODS: Between May
      2009 and February 2010, we collected medical and surgical data about deep
      infiltrating endometriosis resections performed in our institution, using robot
      assisted laparoscopy (DA VINCI Intuitive Surgical System((r))). RESULTS: Six
      patients were included: four partial bladder and two uterosacral ligament
      resections. The median age was 29.5 years (24-48). All patients reported chronic
      pelvic pain, associated with urinary tract symptoms in case of bladder
      endometriosis. Before surgery, lesion mapping was performed using magnetic
      resonance imaging for all, and mechanical bowel preparation or double-j stenting
      were prescribed, depending on the endometriosis location. Surgical procedures
      median time was 173 minutes (156-244), and median length of stay was 3 days (2
      5). Complete resection was possible in all cases. There was no conversion in
      classical laparoscopy or laparotomy, and no intraoperative complication.
      Pathology diagnosis of surgical pieces concluded to endometriosis lesion in all
      cases. CONCLUSION: This study shows the feasibility of the robot-assisted
      laparoscopy in the resection of deep pelvic endometriosis, without increasing of
      surgical timing, blood loss or intraoperative complications.

PMID- 21742536
TI  - [Bakri balloon].
AB  - Uterine tamponade has a place in treatment of postpartum haemorrhage. Bakri
      balloon is the first specifically designed for a uterus cavity and so, to realise
      a tamponade test. This paper reviews the place and the interest of the Bakri
      balloon in the management of postpartum haemorrhage.

PMID- 21742537
TI  - [Prenatal treatment of neonatal hemochromatosis with maternal administration of
      intravenous immunoglobulins (about four cases)].
AB  - OBJECTIVES: Neonatal hemochromatosis is a very bad prognosis disease; liver
      transplantation was the only way to avoid an unfavourable evolution. Nowadays,
      hypothesis of an alloimmune mechanism for this disease has purposed to
      administrate high doses of immunoglobulins. PATIENTS AND METHODS: In this study,
      we report four cases of women whose previous child had neonatal hemochromatosis
      and who received such a treatment during the next pregnancy from 18 weeks to the
      term. RESULTS: This treatment allowed to lead their pregnancy to success. At
      birth, all four neonates were alive. Two of them presented transitory biologic
      symptoms of liver deficiency. All had a favourable evolution later. DISCUSSION
      AND CONCLUSION: Maternal treatment with high doses of immunoglobulins during
      pregnancy seems to improve dramatically the prognosis of neonatal hemochromatosis
      as it has been already reported. It could also apply to other diseases, which
      proceed from the same mechanism.

PMID- 21742538
TI  - Physical features of ultrasound assisted enzymatic degradation of recalcitrant
      organic pollutants.
AB  - This work has attempted to provide answer to the interaction of sonolysis and
      enzymatic treatment on degradation of recalcitrant dyes in a combined treatment.
      The model system comprises of two dyes, acid red and malachite green as model
      pollutants, along with horseradish peroxidase as a model enzyme and ultrasound of
      20 kHz frequency. A dual approach of coupling experimental results with
      simulations of cavitation bubble dynamics has been adopted. Utilization of
      oxidation potential of horseradish peroxidase has been found to be a function of
      convection level in the medium. Cavitation phenomenon is found to have an adverse
      effect on enzyme action due to generation of high amplitude shock waves, which
      denature the enzyme. Degradation of dye at high static pressure increases due to
      absence of cavitation and high energy interaction (or collisions) between enzyme
      and dye molecules, which are beneficial towards enzymatic oxidation of the
      latter. High intensity convection generated by ultrasound also obviates need for
      an external shielding agent such as PEG that prevents attachment of the phenoxy
      radicals to enzyme that blocks the active sites of the enzyme.

PMID- 21742539
TI  - Mechanical properties of suprarenal and infrarenal abdominal aorta: implications
      for mouse models of aneurysms.
AB  - Multiple mouse models have been developed to increase our understanding of the
      natural history of abdominal aortic aneurysms. An advantage of such models is
      that one can quantify the time course of changes in geometry, histology, cell
      biology, and mechanics as a lesion develops. One of the most commonly used mouse
      models yields lesions in the suprarenal abdominal aorta whereas most other models
      target the infrarenal abdominal aorta, consistent with the clinical observation
      that nearly all abdominal aneurysms in humans occur in the infrarenal aorta.
      Understanding reasons for similarities and differences between diverse mouse
      models and human lesions may provide increased insight that would not be possible
      studying a single situation alone. Toward this end, however, we must first
      compare directly the native structure and properties of these two portions of the
      abdominal aorta in the mouse. In this paper, we present the first biaxial
      mechanical data and nonlinear constitutive descriptors for the suprarenal and
      infrarenal aorta in mice, which reveals only subtle mechanical differences
      despite marked morphological and histological differences. Such data promise to
      increase our ability to understand and model the natural history of these deadly
      lesions.

PMID- 21742540
TI  - Seasonality in physical activity: should this be a concern in all settings?
AB  - This study examines the relationship between weather conditions and overall and
      domain-specific physical activity in adults living in a city with a temperate,
      stable climate. Objective and self-reported physical activity levels were
      measured in 1754 adults participating in RESIDE, a longitudinal study undertaken
      in Perth, Australia. Steps per week and self-reported minutes of domain-specific
      physical activity were compared with date-stamped weather data. Weather
      conditions were relatively constant across all seasons, showing little impact on
      physical activity behaviour. Variation in weather conditions had modest
      explanatory power (<6%) for predicting overall and domain-specific physical
      activity engagement in this sample. Weather variations observed in this study
      were of insufficient magnitude to impact on physical activity levels. This has
      implications for study designs and exploration of other factors associated with
      physical activity in these settings.

PMID- 21742541
TI  - The immediate effect of unilateral lumbar Z-joint mobilisation on posterior chain
      neurodynamics: a randomised controlled study.
AB  - Hamstring strain (HS) is a common musculoskeletal condition and abnormal
      neurodynamics has been shown to influence HS and delay recovery. The efficacy of
      stretching for preventing and treating HS remains uncertain despite extensive
      research and wide-spread use. The effects of cervical spine mobilisation on
      peripheral nervous system function, neurodynamics and muscle force in the upper
      limb have been reported. Very few studies have reported effects of lumbar spine
      mobilisation on these variables in the lower limb. This study aimed to determine
      immediate effects of either a unilateral zygopophyseal joint posteroanterior
      mobilisation or a static posterior chain muscle stretch on the range of passive
      straight leg raise (SLR) in comparison to a non-treatment control. Using a single
      blinded, randomised controlled study design, 36 healthy participants were
      allocated into one of three groups (control; mobilisation; static posterior chain
      muscle stretch). Measures of SLR were taken before and after intervention for
      each group on the day of testing. A General Linear Model (GLM) and a paired
      sample t-test showed a significant difference between base line and post
      intervention for the mobilisation group only (p < 0.001), and suggests that
      unilateral lumbar spine zygopophyseal joint mobilisation can immediately restore
      posterior chain neurodynamics.

PMID- 21742542
TI  - Efficient MR image reconstruction for compressed MR imaging.
AB  - In this paper, we propose an efficient algorithm for MR image reconstruction. The
      algorithm minimizes a linear combination of three terms corresponding to a least
      square data fitting, total variation (TV) and L1 norm regularization. This has
      been shown to be very powerful for the MR image reconstruction. First, we
      decompose the original problem into L1 and TV norm regularization subproblems
      respectively. Then, these two subproblems are efficiently solved by existing
      techniques. Finally, the reconstructed image is obtained from the weighted
      average of solutions from two subproblems in an iterative framework. We compare
      the proposed algorithm with previous methods in term of the reconstruction
      accuracy and computation complexity. Numerous experiments demonstrate the
      superior performance of the proposed algorithm for compressed MR image
      reconstruction.

PMID- 21742543
TI  - Semi-automatic liver tumor segmentation with hidden Markov measure field model
      and non-parametric distribution estimation.
AB  - A novel liver tumor segmentation method for CT images is presented. The aim of
      this work was to reduce the manual labor and time required in the treatment
      planning of radiofrequency ablation (RFA), by providing accurate and automated
      tumor segmentations reliably. The developed method is semi-automatic, requiring
      only minimal user interaction. The segmentation is based on non-parametric
      intensity distribution estimation and a hidden Markov measure field model, with
      application of a spherical shape prior. A post-processing operation is also
      presented to remove the overflow to adjacent tissue. In addition to the
      conventional approach of using a single image as input data, an approach using
      images from multiple contrast phases was developed. The accuracy of the method
      was validated with two sets of patient data, and artificially generated samples.
      The patient data included preoperative RFA images and a public data set from "3D
      Liver Tumor Segmentation Challenge 2008". The method achieved very high accuracy
      with the RFA data, and outperformed other methods evaluated with the public data
      set, receiving an average overlap error of 30.3% which represents an improvement
      of 2.3% points to the previously best performing semi-automatic method. The
      average volume difference was 23.5%, and the average, the RMS, and the maximum
      surface distance errors were 1.87, 2.43, and 8.09 mm, respectively. The method
      produced good results even for tumors with very low contrast and ambiguous
      borders, and the performance remained high with noisy image data.

PMID- 21742544
TI  - Recollection, familiarity and memory strength: confusion about confounds.

PMID- 21742545
TI  - News on ABA transport, protein degradation, and ABFs/WRKYs in ABA signaling.
AB  - The recent identification of abscisic acid (ABA) transporters provides an
      important insight into the delivery of ABA from the vascular system and its
      uptake by target cells. A putative connection with PYR/PYL receptors is
      envisaged, linking ABA uptake and intracellular perception by a fast and
      efficient mechanism. Downstream signaling of the core pathway involves regulation
      of ABA-responsive element binding factors (ABFs/AREBs) through phosphorylation,
      ubiquitination, and sumoylation in the case of ABI5. Several E3 ligases appear to
      regulate ABA signaling either positively or negatively, although relatively few
      targets are known yet. ABFs/AREBs are themselves subjected to transcriptional
      regulation, and some transcription factors (TFs) harboring the WRKY domain
      (WRKYs) appear to regulate their expression through W-box sequences present in
      the promoters of ABFs/AREBs.

PMID- 21742546
TI  - Synthesis, characterization and theoretical analysis on a oxygen-sensing
      phosphorescent copper(I) complex.
AB  - In this paper, we report the synthesis, crystal structure, photophysical
      properties, and electronic nature of a phosphorescent Cu(I) complex of [Cu(Phen
      Ph)(PPh(3))(2)]BF(4), where Phen-Ph and PPh(3) stand for 2-phenyl-1H-imidazo[4,5
      f][1,10]phenanthroline and triphenylphosphine, respectively. [Cu(Phen
      Ph)(PPh(3))(2)]BF(4) renders a yellow phosphorescence peaking at 553 nm, with a
      long excited state lifetime of 13.2 MUs under N(2) atmosphere. Density functional
      calculation reveals that the emission comes from a triplet metal-to-ligand-charge
      transfer excited state. We electrospun composite nanofibers of [Cu(Phen
      Ph)(PPh(3))(2)]BF(4) and polystyrene (PS), hoping to explore the possibility of
      using the composite nanofibers as an oxygen sensing material. The finally
      obtained samples with average diameter of ~400 nm exhibit a maximum sensitivity
      of 6.52 towards molecular oxygen with short response time of 15 s due to the
      large surface-area-to-volume ratio of nanofibrous membranes. No photobleaching is
      detected in these samples.

PMID- 21742547
TI  - Acetate recognition by 2,6-bis(2-benzimidazolyl)pyridine.
AB  - 2,6-Bis(2-benzimidazolyl)pyridine, bbp, a simple tridentate ligand, is employed
      as a receptor for the recognition of anions. The binding of anionic guest species
      with bbp can be studied in short duration using UV/vis spectroscopy, fluorescence
      spectroscopy and (1)H NMR techniques at very low concentrations. The results
      obtained from the above spectroscopic techniques indicate that 2,6-bis(2
      benzimidazolyl)pyridine is an efficient anion receptor providing chemical shift
      and optical modification based signals for the detection of acetate ions.

PMID- 21742548
TI  - High lethality of human adenovirus disease in adult allogeneic stem cell
      transplant recipients with high adenoviral blood load.
AB  - BACKGROUND: Human adenoviruses (HAdV) can cause disseminated disease as a severe
      complication after haematopoietic stem cell transplantation (SCT) and may
      originate from the reactivation of latent infections. However, data about the
      clinical relevance of HAdV DNAaemia and disease in adults are scarce. OBJECTIVES:
      To retrospectively analyse the outcome of adult allogeneic SCT recipients with
      high HAdV loads in peripheral blood. STUDY DESIGN: Our diagnostic database was
      screened for allogeneic SCT recipients with peak HAdV DNAaemia above
      1.0*10(4)copies/ml (tested by quantitative real-time PCR) and medical records
      were reviewed retrospectively. RESULTS: From 1674 adult allogeneic SCT recipients
      539 (32.2%) received HAdV DNAaemia testing. In twenty-seven of these HAdV blood
      loads above 1.0*10(4) (range: 1.6*10(4)-1.8*10(9))copies/ml were observed. Seven
      of these 27 succumbed to HAdV disease and their median peak HAdV DNAaemia was
      significantly higher than in patients without HAdV-associated death (1.0*10(8)
      vs. 3*10(5)copies/ml, p<0.001). T-cell depletion was a risk factor for fatal HAdV
      disease. HAdV of species C predominated (66.7%) and were of high virulence (6 of
      7 fatal cases). HAdV of species B were observed more frequently (n=6) in our
      study than reported for paediatrics, indicating a different pattern of HAdV
      reactivation in adults. CONCLUSIONS: The presence of several HAdV-associated
      deaths in adult SCT recipients with high-level HAdV DNAaemia confirmed the
      clinical relevance of HAdV DNAaemia testing in adults. Quantitative HAdV DNAaemia
      testing is a promising tool to predict the outcome of HAdV disease.

PMID- 21742549
TI  - Detection of hepatitis E virus (HEV) from porcine livers in Southeastern Germany
      and high sequence homology to human HEV isolates.
AB  - BACKGROUND: Hepatitis E virus (HEV) has been identified as an emerging cause of
      infectious hepatitis over the last years in developed countries. In contrast to
      travel associated hepatitis E, zoonotic sources of infection are suspected for
      autochthonous cases in Europe. OBJECTIVE: Since pigs are known reservoirs of HEV,
      we tested porcine livers sold as food in Southeastern Germany for the presence of
      hepatitis E virus RNA. STUDY DESIGN: We purchased 200 porcine liver samples in 81
      butcher shops and grocery stores in Regensburg, Germany. Nucleic acid
      preparations were tested for the presence of HEV RNA by quantitative real-time
      PCR (RT-qPCR). HEV isolates from positive samples were characterized by partial
      sequencing of ORF1 and ORF2 regions in the HEV genome and by phylogenetic
      analysis. RESULTS: Specimens from eight (4%) of 200 purchased pig livers had
      detectable HEV RNA amounts. Sequence determination and phylogenetic analysis
      allowed two novel isolates to be classified as HEV genotype 3, subgenotype 3a
      (swR437) and 3c (swR269), respectively. Both novel swine HEV isolates showed high
      sequence homology to isolates obtained from patients with acute HEV infection
      from the same geographic region. CONCLUSIONS: These results support the suggested
      role of undercooked pig products in food as a source of zoonotic HEV infection
      for humans. It remains to be clarified if this mechanism of transmission is
      responsible for the surprisingly high anti-HEV IgG prevalence recently observed
      in some European countries and the USA.

PMID- 21742550
TI  - Metabolism of quercetin by Cunninghamella elegans ATCC 9245.
AB  - Incubation of quercetin with Cunninghamella elegans ATCC 9245 yielded three
      metabolites, including quercetin 3-O-beta-D-glucopyranoside, kaempferol 3-O-beta
      D-glucopyranoside and isorhamnetin 3-O-beta-D-glucopyranoside. Glucosylation, O
      methylation and dehydroxylation were involved in the process, among which
      dehydroxylation has never been found in Cunninghamella. Quercetin was completely
      metabolized in 72 h.

PMID- 21742551
TI  - Effect of antioxidant activity in kimchi during a short-term and over-ripening
      fermentation period.
AB  - This study evaluated the antioxidant activities of kimchi at different
      fermentation times: short-term fermented kimchi (SK; less than 7days) and over
      ripened kimchi (OK; greater than 2 years). In conclusion, antioxidant activity of
      the OK was significantly higher than the SK. The results of this study suggested
      that there was an increase in the antioxidant activity of fermented kimchi during
      the fermentation and ripening processes.

PMID- 21742552
TI  - Influence of copper ions on the viability and cytotoxicity of Pseudomonas
      aeruginosa under conditions relevant to drinking water environments.
AB  - Copper plumbing materials can be the source of copper ions in drinking water
      supplies. The aim of the current study was to investigate the influence of copper
      ions on the viability and cytotoxicity of the potential pathogen Pseudomonas
      aeruginosa that presents a health hazard when occurring in building plumbing
      systems. In batch experiments, exposure of P. aeruginosa (10(6)cells/mL) for 24h
      at 20 degrees C to copper-containing drinking water from domestic plumbing
      systems resulted in a loss of culturability, while total cell numbers determined
      microscopically did not decrease. Addition of the chelator diethyldithiocarbamate
      (DDTC) to copper-containing water prevented the loss of culturability. When
      suspended in deionized water with added copper sulfate (10 MUM), the
      culturability of P. aeruginosa decreased by more than 6 log units, while total
      cell counts, the concentration of cells with intact cytoplasmic membranes,
      determined with the LIVE/DEAD BacLight kit, and the number of cells with intact
      16S ribosomal RNA, determined by fluorescent in situ hybridization, remained
      unchanged. When the chelator DDTC was added to copper-stressed bacteria, complete
      restoration of culturability was observed to occur within 14 d. Copper-stressed
      bacteria were not cytotoxic towards Chinese hamster ovary (CHO-9) cells, while
      untreated and resuscitated bacteria caused an almost complete decrease of the
      concentration of viable CHO-9 cells within 24 h. Thus, copper ions in
      concentrations relevant to drinking water in plumbing systems seem to induce a
      viable but non-culturable (VBNC) state in P. aeruginosa accompanied by a loss of
      culturability and cytotoxicity, and VBNC cells can regain both culturability and
      cytotoxicity, when copper stress is abolished.

PMID- 21742553
TI  - Physical activity and screen time behaviour in metropolitan, regional and rural
      adolescents: a -sectional study of Australians aged 9-16 years.
AB  - OBJECTIVES: While there is consistent evidence that rural adults in Australia are
      less active than their urban counterparts, studies relating geographical
      remoteness to activity patterns in Australian adolescents have yielded
      inconsistent results. The aim of this study was to describe objectively and
      subjectively measured patterns of physical activity and sedentary behaviours
      across remoteness categories in a representative sample of 9-16 year old
      Australians. DESIGN: Cross-sectional observational study. METHODS: 2071
      Australian adolescents provided self-report use of time data on four days and
      wore a pedometer for at least 6 days within the 2007 Australian National
      Children's Nutrition and Physical Activity Survey. Comparisons of activity
      patterns were made across four objectively-determined remoteness categories
      (Major City, Inner Regional, Outer Regional and Remote), adjusting for household
      income, parental education and age. RESULTS: Adolescents living in major cities
      self-reported 11-29 min less moderate to vigorous physical activity each day than
      their counterparts living in geographically more remote areas, and took 150-850
      fewer steps each day. While there were no differences in time spent in sport or
      active transport, differences in free play participation were significant. Males
      in major cities also reported higher levels of screen time. Differences were
      somewhat more marked among males than among females. CONCLUSIONS: Activity levels
      among Australian adolescents show contrasting patterns of geographical
      differences to those found in Australian adults. Higher levels of free play among
      rural Australian adolescents may be due to more available space and less fear of
      traffic and stranger risks.

PMID- 21742554
TI  - Evolution of platinum resistance in high-grade serous ovarian cancer.
AB  - High-grade serous ovarian cancers account for most ovarian-cancer mortality.
      Although this disease initially responds well to platinum-based chemotherapy,
      relapse and progression to chemotherapy resistance are frequently seen. Time to
      relapse after first-line therapy is a predictor of response to secondary platinum
      treatment: more than 12 months is associated with high chance of a secondary
      response, whereas relapses within 6 months generally indicate platinum
      resistance. In this Personal View we discuss whether patterns of response,
      relapse, and the development of drug resistance in high-grade serous ovarian
      cancers are related to distinct underlying molecular and cellular biological
      characteristics. In particular, we propose that rapid relapse with platinum
      resistant disease is due to minor subpopulations of intrinsically resistant
      cancer cells at presentation.

PMID- 21742555
TI  - The rise of cellular therapy.
AB  - In 1938, the field of Transfusion Medicine began as the simpler entity - Blood
      Banking. It was a discipline that focused on collecting, processing, storing and
      distributing end stage blood cells, plasma and plasma fractions to patients. Over
      the years, the field progressed to include clinical patient services such as
      apheresis technology and with the development of stem cell transplantation as a
      standard of care, Cell Therapy. Now the discipline is also finding a niche in the
      area of Regenerative Medicine. The role played by Transfusion Medicine
      practitioners in Cell Therapy and Regenerative Medicine was predicated on many
      factors: (1) pre-existing, established protocols for therapeutic leukapheresis,
      (2) prior experience with mononuclear cell collection and processing, (3) long
      term familiarity with, and a clear understanding of, cGMP and cGLP guidelines,
      Federal regulations, and the voluntary standards established by various
      organizations, (4) close relationships with practitioners in clinical departments
      of medicine, pediatrics, oncology, surgery, and their subspecialty areas. While
      the initial Cell Therapy programs related primarily to hematopoietic stem cell
      transplantation, as Regenerative Medicine programs developed, transfusion
      specialists found it to be a related field that would also benefit from their
      input. Cell Therapy and Regenerative Medicine, now provide fertile soil for the
      seeds of Transfusion Medicine to grow. The once narrowly defined field of Blood
      Banking now encompasses involvement in major new Cellular Therapy/Regenerative
      Medicine research protocols related to treatment of patients with cancer as well
      as renal, hepatic and cardiac illnesses. This in turn provides opportunities for
      residents and fellows to consider robust careers in the field of Transfusion
      Medicine. In this manner we will move forward with one eye on the past and
      another on the promising future.

PMID- 21742556
TI  - Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting
      multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4
      trial.
AB  - BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon
      beta is only partly effective. We aimed to establish whether add-on of
      simvastatin, a statin with anti-inflammatory properties, improves this efficacy.
      METHODS: We enrolled treatment-naive patients with relapsing-remitting multiple
      sclerosis in a multicentre, placebo-controlled, double-blind, randomised,
      parallel-group trial of simvastatin (80 mg daily) as add-on treatment to
      intramuscular interferon beta-1a (30 MUg weekly). After starting treatment with
      interferon beta, patients were randomly assigned (in computer-generated blocks of
      four patients) to simvastatin 80 mg per day or placebo for 1-3 years. Patients
      and treating and evaluating physicians were masked to treatment allocation. The
      primary outcome measure was annual rate of documented relapses; analysis was by
      intention to treat. This trial is registered at ClinicalTrials.gov, NCT00492765.
      FINDINGS: We randomly assigned 307 patients to interferon beta plus simvastatin
      (n=151) or plus placebo (n=156). Annual rate of documented relapses was 0.19 (95%
      CI 0.13 to 0.28) in the simvastatin group and 0.14 (95% CI 0.09 to 0.23) in the
      placebo group (absolute difference 0.059, 95% CI -0.21 to 0.09; p=0.35). Time to
      first documented relapse (20th percentile) was 18.1 months in patients on
      simvastatin and 21.5 months in those on placebo (hazard ratio 1.21, 95% CI 0.74
      to 1.99; p=0.51). Mean number of new or enlarging T2 lesions was 2.96 in the
      simvastatin group and 2.52 in the placebo group (ratio of new lesions, 1.17, 95%
      CI 8.89 to 1.55; p=0.25). Eight (6%) patients on simvastatin and 17 (13%) on
      placebo had no disease activity (odds ratio 0.42, 95% CI 0.17 to 1.00; p=0.05).
      No unexpected adverse events were seen. Generally, adverse events were mild and
      there were no group differences in infections or musculoskeletal disorders,
      including myalgia (five [3%] patients on simvastatin and nine [6%] on placebo).
      Rhabdomyolysis and myoglobinuria were not reported and there were no differences
      in serum creatine phosphokinase. INTERPRETATION: We found no beneficial effect of
      simvastatin as add-on therapy to interferon beta-1a. Although unlikely, we can
      not exclude that combination of other statins with other disease-modifying drugs
      still could be beneficial. FUNDING: Biogen Idec.

PMID- 21742557
TI  - Combining statins with interferon beta in multiple sclerosis: think twice, it
      might not be all right.

PMID- 21742558
TI  - Benign cystic lesions in the testis of children.
AB  - Cystic lesions in the testis of children are rare and in most cases benign
      tumors. However, a preoperative diagnostic work-up could contribute to planning
      the surgical procedure: orchiectomy in the case of potential malignancy or
      otherwise a testis-sparing approach. In this study we reviewed our recent cases
      of benign cystic testicular tumors and the corresponding literature. The
      different entities are presented with details of the diagnostic work-up,
      pathology and treatment of these lesions. In all presented cases, organ
      preserving treatment was performed. This practice is to be recommended in the
      case of all prepubertal cystic testicular lesions.

PMID- 21742559
TI  - Dalfampridine in multiple sclerosis: from symptomatic treatment to
      immunomodulation.
AB  - Multiple sclerosis (MS) is a neurodegenerative disease that is deemed to affect
      more than 2.1 million people worldwide, and for which there is no cure. Early
      symptoms of MS are believed to result from axonal demyelination leading to
      slowing or blockade of impulse conduction. The blockade of K+ channels has been
      proven to improve conduction deficiencies secondary to demyelination in patients
      with MS. Dalfampridine is a K+ channel blocker that was recently approved by FDA
      for the symptomatic treatment of ambulation hardship in MS. Understanding the
      mechanisms by which Dalfampridine exerts its therapeutic effects is a complex
      issue as it blocks a wide variety of K+ channels that are distributed across
      multiple cell types in the nervous system but also in the immune system, and
      because of their molecular identities remaining unknown. This review describes
      Dalfampridine potential roles at the cellular and molecular levels in MS
      pathogenesis.

PMID- 21742560
TI  - Pathology of mixed Mullerian tumours.
AB  - The term 'mixed Mullerian tumour' applies to uterine tumours composed of
      epithelial and mesenchymal elements of Mullerian origin. These neoplasms are
      classified into adenomyomas, adenofibromas, adenosarcomas, and carcinosarcomas
      (malignant Mullerian mixed tumours) based on whether the epithelial and stromal
      elements are benign or malignant. The rare atypical polypoid adenomyoma usually
      involves the lower uterine segment and, on curettings, may be confused with
      invasive adenocarcinoma. Adenosarcomas are low-grade neoplasms classified halfway
      along the spectrum of mixed Mullerian tumours, with adenofibromas at one end and
      carcinosarcomas (malignant Mullerian mixed tumours) at the other. Some tumours
      currently classified as 'adenofibromas' on the basis of their low mitotic count
      and lack of nuclear atypia are, in fact, well differentiated adenosarcomas.
      Carcinosarcoma is composed of admixed but distinctive carcinomatous and
      sarcomatous elements. On the basis of the clonal origin of both tumour
      components, carcinosarcomas are currently thought to be metaplastic carcinomas
      rather than uterine sarcomas.

PMID- 21742561
TI  - Explicit and implicit emotional processing modifications in pharmacoresistant
      left temporal lobe epilepsy and anxiodepressive disorders.
AB  - We examined whether anxiodepressive patients with left temporal lobe epilepsy
      could be differentiated from those with depression but without epilepsy on tasks
      that investigate attentional bias toward and explicit judgment of emotional
      stimuli. Eight depressive patients, eight anxiodepressive patients with epilepsy,
      and eight controls participated in the present study. Anxiodepressive with
      epilepsy and depressive patients had comparable depression scores and the same
      cognitive profile. Two distinct emotional tasks were used: the decision lexical
      task and the number comparison task. Three emotional connotations were presented:
      neutral, positive, and negative. The pattern of results showed an attentional
      bias toward negative words and pictures in depressive patients and only toward
      negative words in anxiodepressive patients with epilepsy. Moreover, depressive
      patients explicitly judged negative stimuli with lower intensity and
      anxiodepressive patients judged neutral stimuli with higher intensity. The
      present study specifies the emotional functioning in depression with or without
      left temporal lobe epilepsy.

PMID- 21742562
TI  - Depression screening for patients with epilepsy in a primary care setting using
      the Patient Health Questionnaire-2 and the Neurological Disorders Depression
      Inventory for Epilepsy.
AB  - Depression among people with a diagnosis of epilepsy is under-recognized. General
      practitioner (GP) screening for depression using a new scale developed
      specifically for patients with epilepsy, the Neurological Disorders Depression
      Inventory for Epilepsy (NDDI-E), has not before been reported. The aims were to
      examine the process of GP screening for depression in patients with epilepsy
      employing the widely used Patient Health Questionnaire-2 (PHQ-2) and the NDDI-E;
      to determine the impact of screening on GP-recognized depression; and to
      ascertain depression predictors. Patients were screened via their GPs. A subset
      of participants underwent clinical interview to assess screener accuracy. Use of
      either instrument almost doubled the proportion of GP-recognized depression.
      Ninety-four percent of those interviewed found screening acceptable. More recent
      and frequent seizures predicted screening positive. The results suggest that
      screening for depression in patients with epilepsy via GPs improves detection of
      depression and is acceptable to interviewed patients.

PMID- 21742563
TI  - Guideline warfare over interventional therapies for low back pain: can we raise
      the level of discourse?
AB  - As guidelines proliferate and are used to inform efforts to improve the quality
      and efficiency of care, disputes over guideline recommendations are likely to
      become more common and contentious. It is appropriate for guidelines to come
      under close scrutiny, given their important clinical and policy implications, and
      critiques that point out missing evidence, improper methods, or errors in
      interpretation can be valuable. But for critiques to be valid, they should be
      based on accurate information and a sound scientific basis. A 2009 guideline
      sponsored by the American Pain Society (APS) on the use of invasive tests and
      interventional procedures found insufficient evidence to make recommendations for
      most interventional procedures. It was subsequently the subject of lengthy
      critiques by the American Society of Interventional Pain Physicians (ASIPP) that
      sought to challenge the methods used to develop the APS guideline, point out
      alleged errors in the evidence review commissioned to inform the guideline, and
      question the integrity of the APS guideline process. We show that the ASIPP
      critiques contain numerous errors and fail to adhere to scientific standards for
      reviewing evidence, and provide suggestions on how future disputes regarding
      guidelines might be addressed in a more constructive manner. PERSPECTIVE: In
      order to best serve patients and clinicians, debates over guidelines should be
      based on accurate information, adhere to current methodological standards,
      acknowledge important deficiencies in the evidence when they are present, and
      handle conflicts of interest in a vigorous and transparent manner.

PMID- 21742564
TI  - Simultaneous determination of thiamphenicol, florfenicol and florfenicol amine in
      eggs by reversed-phase high-performance liquid chromatography with fluorescence
      detection.
AB  - A specific, sensitive and widely applicable reversed-phase high-performance
      liquid chromatography with fluorescence detection (RP-HPLC-FLD) method was
      developed for the simultaneous determination of thiamphenicol (TAP), florfenicol
      (FF) and florfenicol amine (FFA) in eggs. Samples were extracted with ethyl
      acetate-acetonitrile-ammonium hydroxide (49:49:2, v/v), defatted with hexane,
      followed by RP-HPLC-FLD determination. Liquid chromatography was performed on a 5
      MUm LiChrospher C(18) column using a mobile phase composed of acetonitrile (A),
      0.01 M sodium dihydrogen phosphate containing 0.005 M sodium dodecyl sulfate and
      0.1% triethylamine, adjusted to pH 4.8 by 85% phosphoric acid (B) (A:B, 35:65
      v/v), at a flow rate of 1.0 mL/min. The fluorescence detector of HPLC was set at
      224 nm for excitation wavelength and 290 nm for emission wavelength. Limits of
      detection (LODs) were 1.5 MUg/kg for TAP and FF, 0.5 MUg/kg for FFA in eggs;
      limits of quantitation (LOQs) were 5 MUg/kg for TAP and FF, 2 MUg/kg for FFA in
      eggs. Linear calibration curves were obtained over concentration ranges of 0.025
      5.0 MUg/mL for TAP with determination coefficients of 0.9997, 0.01-10.0 MUg/mL
      for FF with determination coefficients of 0.9997 and 0.0025-2.50 MUg/mL for FFA
      with determination coefficients of 0.9998, respectively. The recovery values
      ranged from 86.4% to 93.8% for TAP, 87.4% to 92.3% for FF and from 89.0% to 95.2%
      for FFA. The corresponding intra-day and inter-day variation (relative standard
      deviation, R.S.D.) found to be less than 6.7% and 10.8%, respectively.

PMID- 21742565
TI  - Intercalary defects reconstruction of the femur and tibia after primary malignant
      bone tumour resection. A series of 13 cases.
AB  - INTRODUCTION: Performing intercalary segment reconstruction after malignant bone
      tumour resection results in both mechanical and biological challenges. Fixation
      must be solid enough to avoid short-term or mid-term mechanical failure. The use
      of an allograft or autograft must ensure long-term survival of the
      reconstruction. The goal of this study was to analyse the clinical and
      radiological outcomes of these reconstructions. PATIENTS AND METHODS: Thirteen
      patients were operated on eight femurs and five tibias. The median age was 20
      years old (range 14-50). The most common diagnosis was osteosarcoma. The median
      resection length was 15cm (Q1-Q3: 6-26). A plate was used for fixation in nine
      cases and an intramedullary locked nail in four cases. An isolated bone autograft
      was used in two cases, an isolated bone allograft in one case, a dual autograft
      allograft composite in six cases, and vascularised fibula and allograft
      combination in four cases. RESULTS: The cumulative probability of union was 46%
      (95% CI: 0-99%) at 1 year; at the final follow-up, union was achieved in 12
      patients (92%). Because of non-unions, 13 iterative procedures were needed to
      obtain these results. A non-displaced fracture of a cuboid-shaped tibial graft
      occurred in one patient, which was treated conservatively. Three infections
      occurred. DISCUSSION: The results of intercalary segmental defects reconstruction
      after bone tumour resection were good, both from an oncologic and radiological
      point-of-view. One or more iterative procedures are sometimes needed to finally
      obtain bone union. We prefer to use a free rectangular cuboidal tibial graft
      since reconstruction with a vascularised autograft is technically more difficult.
      The choice of fixation methods is still controversial and no approach was found
      to be superior. LEVEL OF EVIDENCE: Level IV. Retrospective study.

PMID- 21742566
TI  - Constipation and colonic transit in Mexican patients.

PMID- 21742567
TI  - Protein interaction hotspot identification using sequence-based frequency-derived
      features.
AB  - Finding good descriptors, capable of discriminating hotspot residues from others,
      is still a challenge in many attempts to understand protein interaction. In this
      paper, descriptors issued from the analysis of amino acid sequences using digital
      signal processing (DSP) techniques are shown to be as good as those derived from
      protein tertiary structure and/or information on the complex. The simulation
      results show that our descriptors can be used separately to predict hotspots, via
      a random forest classifier, with an accuracy of 79% and a precision of 75%. They
      can also be used jointly with features derived from tertiary structures to boost
      the performance up to an accuracy of 82% and a precision of 80%. 

PMID- 21742568
TI  - Correlation between P-wave morphology and origin of atrial focal tachycardia-
      insights from realistic models of the human atria and torso.
AB  - Atrial arrhythmias resulting from abnormally rapid focal activity in the atria
      may be reflected in an altered P-wave morphology (PWM) in the ECG. Although
      clinically important, detailed relationships between PWM and origins of atrial
      focal excitations have not been established. To study such relationships, we
      developed computational models of the human atria and torso. The model simulation
      results were used to evaluate an extant clinical algorithm for locating the
      origin of atrial focal points from the ECG. The simulations showed that the
      algorithm was practical and could predict the atrial focal locations with 85%
      accuracy. We proposed a further refinement of the algorithm to distinguish
      between focal locations within the large atrial bundles.

PMID- 21742569
TI  - Hyperconnections and hierarchical representations for grayscale and multiband
      image processing.
AB  - Connections in image processing are an important notion that describes how pixels
      can be grouped together according to their spatial relationships and/or their
      gray-level values. In recent years, several works were devoted to the development
      of new theories of connections among which hyperconnection (h-connection) is a
      very promising notion. This paper addresses two major issues of this theory.
      First, we propose a new axiomatic that ensures that every h-connection generates
      decompositions that are consistent for image processing and, more precisely, for
      the design of h-connected filters. Second, we develop a general framework to
      represent the decomposition of an image into h-connections as a tree that
      corresponds to the generalization of the connected component tree. Such trees are
      indeed an efficient and intuitive way to design attribute filters or to perform
      detection tasks based on qualitative or quantitative attributes. These
      theoretical developments are applied to a particular fuzzy h-connection, and we
      test this new framework on several classical applications in image processing,
      i.e., segmentation, connected filtering, and document image binarization. The
      experiments confirm the suitability of the proposed approach: It is robust to
      noise, and it provides an efficient framework to design selective filters.

PMID- 21742570
TI  - An unenumerative DNA computing model for vertex coloring problem.
AB  - The solution space exponential explosion caused by the enumeration of the
      candidate solutions maybe is the biggest obstacle in DNA computing. In the paper,
      a new unenumerative DNA computing model for graph vertex coloring problem is
      presented based on two techniques: 1) ordering the vertex sequence for a given
      graph in such a way that any two consecutive labeled vertices i and i+1 should be
      adjacent in the graph as much as possible; 2) reducing the number of encodings
      representing colors according to the construture of the given graph. A graph with
      12 vertices without triangles is solved and its initial solution space includes
      only 283 DNA strands, which is 0.0532 of 3(12) (the worst complexity).

PMID- 21742571
TI  - SOMRuler: a novel interpretable transmembrane helices predictor.
AB  - Transmembrane helices (TMH) identification is one of the most important steps in
      membrane protein structure prediction. Existing TMH predictors tend to pursue
      accurate computational models without carefully considering the interpretability
      of these models and thus act as a black box. In this paper, a novel TMH predictor
      called SOMRuler with excellent interpretability while possessing high prediction
      accuracy is presented. The SOMRuler uses a self-organizing map (SOM) to learn
      helices distribution knowledge, which is encoded in the codebook vectors of the
      trained SOM, from the training samples. Human interpretable fuzzy rules are then
      extracted from the codebook vectors of the trained SOM. By extracting fuzzy rules
      from the learned knowledge rather than the original training samples, on the one
      hand, the computational burden of extracting fuzzy rules can be greatly reduced;
      on the other hand, the reliability of the extracted rules can also be enhanced
      since noise contained in the original samples can be smoothened by the learning
      procedure of SOM. The validity of the fuzzy rules extracted by SOMRuler is
      qualitatively and quantitatively analyzed. Experimental results on the benchmark
      dataset show that the SOMRuler outperforms most existing popular TMH predictors
      and is flexible to suite for a wide variety of problems in bioinformatics. The
      SOMRuler software is implemented by Java and Matlab and is available for academic
      use at: http://www.csbio.sjtu.edu.cn/bioinf/SOMRuler/.

PMID- 21742572
TI  - A new branch and bound method for the protein folding problem under the 2D-HP
      model.
AB  - The protein folding problem is a fundamental problem in computational molecular
      biology and biochemical physics. The previously best known branch and bound
      method for the protein folding problem may find optimal or near-optimal energy
      structure from the benchmark sequences, but the total computation time is rather
      lengthy because it usually needs to run a great deal of simulating tests or else
      lack of accuracy. In this paper, we develop a new branch and bound method for the
      the protein folding problem under the two-dimensional HP model to overcome the
      mentioned drawbacks. By using benchmark sequences for evaluation, we demonstrate
      that the performance of our method is superior than previously known methods.
      Moreover, our method is a simple, flexible and easily implemented one for the
      protein folding problem.

PMID- 21742573
TI  - Tumor classification based on non-negative matrix factorization using gene
      expression data.
AB  - This paper presents a new method for tumor classification using gene expression
      data. In the proposed method, we first select genes using nonnegative matrix
      factorization (NMF) or sparse NMF (SNMF), and then we extract features from the
      selected genes by virtue of NMF or SNMF. At last, we apply support vector
      machines (SVM) to classify the tumor samples using the extracted features. In
      order for a better classification, a modified SNMF algorithm is also proposed.
      The experimental results on benchmark three microarray data sets validate that
      the proposed method is efficient. Moreover, the biological meaning of the
      selected genes are also analyzed.

PMID- 21742574
TI  - Knowledge based cluster ensemble for cancer discovery from biomolecular data.
AB  - The adoption of microarray techniques in biological and medical research provides
      a new way for cancer diagnosis and treatment. In order to perform successful
      diagnosis and treatment of cancer, discovering and classifying cancer types
      correctly is essential. Class discovery is one of the most important tasks in
      cancer classification using biomolecular data. Most of the existing works adopt
      single clustering algorithms to perform class discovery from biomolecular data.
      However, single clustering algorithms have limitations, which include a lack of
      robustness, stability, and accuracy. In this paper, we propose a new cluster
      ensemble approach called knowledge based cluster ensemble (KCE) which
      incorporates the prior knowledge of the data sets into the cluster ensemble
      framework. Specifically, KCE represents the prior knowledge of a data set in the
      form of pairwise constraints. Then, the spectral clustering algorithm (SC) is
      adopted to generate a set of clustering solutions. Next, KCE transforms pairwise
      constraints into confidence factors for these clustering solutions. After that, a
      consensus matrix is constructed by considering all the clustering solutions and
      their corresponding confidence factors. The final clustering result is obtained
      by partitioning the consensus matrix. Comparison with single clustering
      algorithms and conventional cluster ensemble approaches, knowledge based cluster
      ensemble approaches are more robust, stable and accurate. The experiments on
      cancer data sets show that: 1) KCE works well on these data sets; 2) KCE not only
      outperforms most of the state-of-the-art single clustering algorithms, but also
      outperforms most of the state-of-the-art cluster ensemble approaches.

PMID- 21742575
TI  - Secondhand smoke exposure and coronary artery calcification among nonsmoking
      participants of a population-based cohort.
AB  - BACKGROUND: Secondhand smoke (SHS) consists of fine particulate matter,
      carcinogens, and various toxins that affect large parts of the population. SHS
      increases the risk for acute cardiovascular events and may contribute to the
      development of atherosclerosis. OBJECTIVES: We investigated the association of
      SHS with coronary artery calcification (CAC). METHODS: In this cross-sectional
      analysis, we used baseline data (2000-2003) from 1,766 never-smokers without
      clinically manifested coronary heart disease, 45-75 years of age, from the Heinz
      Nixdorf Recall Study, an ongoing, prospective, population-based cohort study in
      Germany. Self-reported frequent SHS at home, at work, and in other places was
      assessed by questionnaire. CAC scores were derived based on electron-beam
      computed tomography. We conducted multiple linear regression analysis using
      exposure to SHS as the explanatory variable and ln(CAC+1) as the response
      variable. We conducted logistic regression to estimate the odds ratio (OR) for
      presence of any CAC. RESULTS: Frequent exposure to SHS was reported by 21.5% of
      participants. After adjustment for age, sex, and socioeconomic status, CAC + 1
      was 21.1% [95% confidence interval (CI): -5.5%, 55.2%] higher in exposed than in
      unexposed participants. After adjusting for other cardiovascular risk factors,
      the association was attenuated (15.4%; 95% CI: -9.6%, 47.2%). SHS exposure was
      also associated with a CAC score > 0 (fully adjusted OR = 1.38; 95% CI: 1.03,
      1.84). CONCLUSIONS: Self-reported frequent exposure to SHS was associated with
      subclinical coronary atherosclerosis in our cross-sectional study population.
      Considering the widespread exposure and the clinical relevance of coronary
      atherosclerosis, this result, if confirmed, is of public health importance.

PMID- 21742576
TI  - Arsenic exposure and motor function among children in Bangladesh.
AB  - BACKGROUND: Several reports indicate that drinking water arsenic (WAs) and
      manganese (WMn) are associated with children's intellectual function. Very little
      is known, however, about possible associations with other neurologic outcomes
      such as motor function. METHODS: We investigated the associations of WAs and WMn
      with motor function in 304 children in Bangladesh, 8-11 years of age. We measured
      As and Mn concentrations in drinking water, blood, urine, and toenails. We
      assessed motor function with the Bruininks-Oseretsky test, version 2, in four
      subscales-fine manual control (FMC), manual coordination (MC), body coordination
      (BC), and strength and agility-which can be summarized with a total motor
      composite score (TMC). RESULTS: Log-transformed blood As was associated with
      decreases in TMC [beta = -3.63; 95% confidence interval (CI): -6.72, -0.54; p <
      0.01], FMC (beta = -1.68; 95% CI: -3.19, -0.18; p < 0.05), and BC (beta = -1.61;
      95% CI: -2.72, -0.51; p < 0.01), with adjustment for sex, school attendance, head
      circumference, mother's intelligence, plasma ferritin, and blood Mn, lead, and
      selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also
      were inversely associated with motor function scores, particularly TMC and BC.
      Square-transformed blood selenium was positively associated with TMC (beta =
      3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (beta = 1.55; 95% CI: 0.40, 2.70; p <
      0.005), and MC (beta = 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted
      models. Mn exposure was not significantly associated with motor function.
      CONCLUSION: Our research demonstrates an adverse association of As exposure and a
      protective association of Se on motor function in children.

PMID- 21742577
TI  - Status of legislation and regulatory control of public health pesticides in
      countries endemic with or at risk of major vector-borne diseases.
AB  - BACKGROUND: Legislation and regulation of pesticides used in public health are
      essential for reducing risks to human health and the environment. OBJECTIVE: We
      assessed the global situation on legislation and regulatory control of public
      health pesticides. METHODS: A peer-reviewed and field-tested questionnaire was
      distributed to 142 member states of the World Health Organization (WHO); 113
      states completed the questionnaire. RESULTS: Legislation on public health
      pesticides was absent in 25% of the countries. Where present, legislation often
      lacked comprehensiveness, for example, on basic aspects such as labeling,
      storage, transport, and disposal of public health pesticides. Guidelines or
      essential requirements for the process of pesticide registration were lacking in
      many countries. The capacity to enforce regulations was considered to be weak
      across WHO regions. Half of all countries lacked pesticide quality control
      laboratories, and two-thirds reported high concern over quality of products on
      the market. National statistics on production and trade of pesticides and
      poisoning incidents were lacking in many countries. Despite the shortcomings, WHO
      recommendations were considered to constitute a supportive or sole basis in
      national registration. Also, some regions showed high participation of countries
      in regional schemes to harmonize pesticide registration requirements.
      CONCLUSIONS: Critical deficiencies are evident in the legislative and regulatory
      framework for public health pesticides across regions, posing risks to human
      health and the environment. Recent experience in some countries with situational
      analysis, needs assessment, action planning, and regional collaboration has
      signaled a promising way forward.

PMID- 21742578
TI  - Acute otitis media in neonatal life: a review.
AB  - Acute otitis media is frequently encountered by general practitioners and
      pediatricians. In the neonatal period acute otitis media may present as an
      isolated local infection or as part of septicemia. Diagnosis of the condition by
      otoscopy is difficult. Considering the wide spectrum of middle ear disorders
      (acute otitis media, otitis media with effusion, chronic suppurative otitis
      media) one can appreciate why opinions on the management of the condition are
      diverse. This is a review of the literature on clinical presentation, etiology,
      risk factors, treatment and prevention of acute otitis media in neonatal life.

PMID- 21742579
TI  - First report of a novel extended-spectrum beta-lactamase KOXY-2 producing
      Klebsiella oxytoca that hydrolyses cefotaxime and ceftazidime.
AB  - Klebsiella oxytoca strains MU946294N and MB193997E were isolated from patients in
      Scotland. Strain MU946294N was resistant to pencillins, monbactams and
      cephalosporins. Isolate MB193997E displayed a beta-lactam resistance phenotype
      consistent with chromosomal beta-lactamase overproduction. No bla(TEM), bla(SHV)
      or bla(CTX-M) genes could be amplified in either strain; however, amplification
      by PCR was found with primers for the bla(OXY-2) gene. This beta-lactamase gene
      in MU946294N differed by one mutation from the all other bla(OXY) genes
      previously reported, with an amino acid substitution Alanine237 Threonine
      enhancing the binding of cefotaxime. Strain MB193997E showed mutations at
      positions 255 and 283, neither of which affect function. Based on rpoB and gyrA
      characterization, both strains were assigned to the KoII phylogenic group but
      they were completely dissimilar from each other by PFGE. This study is the first
      to report the substitution of Alanine to Threonine at position 237 in a OXY- 2
      beta-lactamase and this enhances resistance to cefotaxime.

PMID- 21742580
TI  - Prevalence of integrons, blaCTX-M and blaTEM resistance markers among ESBL
      producing uropathogenic Escherichia coli isolates: first report of genomic blaCTX
      M from India.
AB  - Integrons have been observed to be frequently associated with uropathogenic
      bacteria. This study aimed at 1) determining the prevalence of class 1 integrons
      among ESBLl-producing uropathogenic Escherichia coli, and 2) analyzing resistance
      genes associated with different phylogenetic groups of the integron-positive
      isolates with special reference to bla(CTX-M) and bla(TEM). Twenty-three ESBL
      producing E. coli were studied. Enterobacterial repetitive intergenic consensus
      PCR (ERIC-PCR) displayed 14 major patterns. Pulse field Gel electrophoresis
      typing of 8 randomly selected integron-positive strains ruled out any correlation
      between genotype and antibiotype. Genomic DNA from 14 strains was PCR-positive
      for class 1 integrons, bla(CTX-M-15) and bla(TEM-1)-like genes. Integron
      sequencing revealed "aadA5-dfrA17-dfrA7" as the most prevalent gene cassette. Our
      findings unveil the increasing role of the bla(CTX-M) genes in antibiotic
      resistance and emphasize on the significance of appropriate empirical treatment
      for Urinary tract infections. Moreover, this is the first study which reports
      bla(CTX-M) located on genomic DNA of bacteria from India.

PMID- 21742581
TI  - Phenotypic changes in a laboratory-derived ertapenem-resistant Escherichia coli
      strain.
AB  - The aim of this study was to identify phenotypic changes in a laboratory-derived
      strain of ertapenem-resistant Escherichia coli (Ec-ERT) when compared to its
      susceptible parent strain (Ec-WT). In both strains, we assessed both the effects
      of ertapenem via time-kill curves and the occurrence of cross resistance with
      other beta-lactams. The strains were compared based on growth pattern,
      biochemical-physiological profile and changes in the subproteome using 2D-DIGE
      followed by MALDI-TOF/TOF MS. To assess virulence, we employed a murine model of
      intraperitoneal infection in which we investigated the invasiveness of both
      strains. Growth persistence of the laboratory-derived resistant strain was
      observed via the time-kill curve assay, but cross resistance was not observed for
      other beta-lactams. We also observed a slower growth rate and changes in the
      biochemical and physiological characteristics of the drug-resistant bacteria. In
      the resistant strain, a total of 51 protein spots were increased in abundance
      relative to the wild-type strain, including an outer membrane protein A, which is
      related to bacterial virulence. The mouse infection assay showed a higher
      invasiveness of the Ec-ERT strain in relation to the Ec-WT strain. In conclusion,
      the alterations driven by ertapenem in E. coli reinforce the idea that
      antimicrobial agents may interfere in several aspects of bacterial cell biology,
      with possible implications for host-bacteria interactions.

PMID- 21742582
TI  - The antistaphylococcal pharmacodynamics of linezolid alone and in combination
      with doxycycline in an in vitro dynamic model.
AB  - To delineate the possible advantages of linezolid/doxycycline combinations over
      either drug alone, the in vitro pharmacodynamics of linezolid, doxycycline and
      linezolid plus doxycycline were studied with Staphylococcus aureus.S. aureus ATCC
      43300 and a clinical isolate S. aureus 479 were exposed to twice-daily linezolid
      and once-daily doxycycline, alone and in combination, for five consecutive days.
      Three dosing regimens were simulated with each drug alone: linezolid (AUC(24)/MIC
      30, 60 and 200 h-L30, L60 and L200, respectively) and doxycycline (AUC(24)/MIC
      90, 180 and 520 h - D90, D180 and D520, respectively) and in combination:
      linezolid plus doxycycline (L30+D90; L60+D180 and L200+D520).With both S. aureus
      ATCC 43300 and S. aureus 479 exposed to linezolid or doxycycline, the area
      between the line crossing each time-kill curve at the level of 10(8) CFU/mL and
      the respective time-kill curve (I(E)) increased with increasing simulated
      AUC(24)/MIC ratios. Each of the combined treatments produced greater I(E)s than
      the sum of linezolid and doxycycline I(E)s observed in the respective single drug
      treatments.This study suggests that linezolid combinations with doxycycline may
      be synergistic in treating staphylococcal infections.

PMID- 21742583
TI  - Comparative effects of the immediate and the extended release formulations of
      ciprofloxacin on normal human intestinal microflora.
AB  - Ciprofloxacin is a well-known fluoroquinolone, active in vitro against most Gram
      negative and Gram-positive bacteria. The purpose of the present study was to
      evaluate the ecological effects of an orally administered extended-release
      formulation of ciprofloxacin in comparison with an immediate-release formulation
      of ciprofloxacin on the normal human intestinal microflora. Thirty-six healthy
      female subjects were included in the study. the extended-release formulation of
      ciprofloxacin was given as 500 mg once daily and the immediate-release
      formulation as 250 mg twice daily. The treatment period was 3 days. the
      microbiological investigation was blinded with respect to treatment. Mean fecal
      concentration in the volunteers receiving the extended-release formulation
      ciprofloxacin was 453 mg/kg and in the immediate-release formulation
      ciprofloxacin volunteers, the mean fecal concentration was 392 mg/kg. The numbers
      of Escherichia coli were significantly suppressed while the enterococci decreased
      moderately in both treatment groups. No toxigenic Clostridium difficile strains
      were found. No major differences were observed between the two studied
      formulations on the normal human intestinal microflora.

PMID- 21742584
TI  - Maesopsin 4-O-beta-D-glucoside, a natural compound isolated from the leaves of
      Artocarpus tonkinensis, inhibits proliferation and up-regulates HMOX1, SRXN1 and
      BCAS3 in acute myeloid leukemia.
AB  - The leaves of Artocarpus tonkinensis are used in Vietnamese traditional medicine
      for treatment of arthritis, and the compound maesopsin 4-O-beta-D-glucoside (TAT
      2), isolated from them, inhibits the proliferation of activated T cells. Our goal
      was to test the anti-proliferative activity of TAT-2 on the T-cell leukemia,
      Jurkat, and on the acute myeloid leukemia, OCI-AML. TAT-2 inhibited the growth of
      OCI-AML (and additional acute myeloid leukemia cells) but not Jurkat cells.
      Growth inhibition was shown to be due to inhibition of proliferation rather than
      increase in cell death. Analysis of cytokine release showed that TAT-2 stimulated
      the release of TGF-beta, yet TGF-beta neutralization did not reverse the
      maesopsin-dependent effect. Gene expression profiling determined that maesopsin
      modulated 19 identifiable genes. Transcription factor CP2 was the gene most
      significantly modulated. Real-time PCR validated that up-regulation of
      sulphiredoxin 1 homolog (SRXN1), hemeoxygenase 1 (HMOX1), and breast carcinoma
      amplified sequence 3 (BCAS3) were consistently modulated.

PMID- 21742585
TI  - Pegylated liposomal doxorubicin (Caelyx(r)) and oral vinorelbine in first-line
      metastatic breast cancer patients previously treated with anthracyclines.
AB  - Doxorubicin is highly effective and widely used in breast cancer; however, its
      use is limited by cardiotoxicity related to its cumulative dose. In previous
      studies, pegylated liposomal doxorubicin (PLD) has shown an acceptable toxicity
      profile with minimal cardiotoxicity. Between June 2006 and October 2009, 27
      metastatic breast cancer patients were treated with first-line PLD and
      vinorelbine at the University of Florence, Radiotherapy Unit. PLD (30 mg/m2) was
      administered on day 1, and oral vinorelbine (60 mg/m2) was administered on days 1
      and 8 of a 4-week cycle. All patients were previously treated with anthracycline
      based adjuvant chemotherapy. Median age was 52 years (range 38-69) and median
      time to metastasis was 78.5 months. There were no treatment interruptions or
      discontinuation for cardiac toxicity and no treatment-related deaths. Grade 3
      hematological toxicity was observed in 18.6% of patients, and 3.7% had grade 3
      non-hematological adverse events. With a median follow-up of 13.2 months (range 3
      33), median response duration was 6.1 months, and median PFS was 5.3 months. The
      overall clinical benefit rate was 55.5%. Our experience adds to evidence
      supporting the activity and cardiac safety of PLD and vinorelbine in metastatic
      breast cancer patients previously treated with anthracycline-based adjuvant
      chemotherapy.

PMID- 21742586
TI  - Feasibility of intravenous gemcitabine and an intraperitoneal platinum agent in
      the treatment of ovarian cancer.
AB  - The goal of this study is to determine the feasibility of intravenous gemcitabine
      and an intraperitoneal platinum agent in the treatment of patients with ovarian
      cancer. We performed a retrospective chart review of patients with primary,
      persistent or recurrent ovarian cancer, who received intravenous gemcitabine and
      an intraperitoneal platinum agent. Patients received gemcitabine (750 mg/m2)
      intravenous on days 1 and 8 and cisplatin (100 or 60 mg/m2) intraperitoneal on
      day 1 every 21 - 28 days. An alternate regimen was composed of gemcitabine (750
      mg/m2) intravenous and carboplatin (AUC 5) intraperitoneal on day 1 every 21
      days. Dose reductions occurred at the discretion of the prescribing
      physician.Intravenous gemcitabine and an intraperitoneal platinum agent were
      administered to 12 patients with advanced primary or recurrent ovarian cancer.
      Myelosuppression was the most common toxicity. Grade 3 or 4 thrombocytopenia,
      neutropenia and anemia occurred in 7, 8 and 2 patients respectively. Dose
      reductions were required in 7 of 12 patients. 10 of 12 patients received 6 cycles
      of the regimen. Treatment was discontinued prior to 6 cycles in 2 of 12 patients
      secondary to progression in one case and to grade 4 neutropenia and
      thrombocytopenia in another.The combination of intravenous gemcitabine and an
      intraperitoneal platinum agent appears to be a feasible regimen in patients with
      ovarian cancer. The most common toxicity was myelosuppression, which resulted in
      dose reductions in almost half of the patients.

PMID- 21742587
TI  - Tigecycline treatment for urinary tract infections: case report and literature
      review.
AB  - Antimicrobial resistance among Gram-negatives is increasing; treatment options
      are limited. Although tigecycline is used infrequently for urinary tract
      infection (UTI), greater use is likely as resistance increases. We report
      successful treatment of an episode of febrile UTI and probable prostatitis with
      tigecycline, and summarize the relevant literature.

PMID- 21742588
TI  - Multidrug-resistant Gram-negative bacilli causing urinary tract infections:
      clinical considerations.

PMID- 21742589
TI  - Activity of drugs against dormant Mycobacterium tuberculosis.

PMID- 21742590
TI  - Prostatic penetration of meropenem after intravenous administration in patients
      undergoing transurethral resection of the prostate.

PMID- 21742591
TI  - First report from Italy of blaVIM-1 and blaTEM-1 genes in Pseudomonas putida and
      Acinetobacter baumannii isolated from wastewater.

PMID- 21742592
TI  - Thrombocytopenia, INR prolongation and fall in fibrinogen under daptomycin.

PMID- 21742593
TI  - [PI3K-AKT-mTOR pathway and cancer].
AB  - PI3K/AKT/mTOR pathway is an intracellular signalling pathway composed of
      different kinases. Many protein mutations are described in that pathway, and are
      responsible of dysregulation of cell growth, proliferation, survival and
      angiogenesis. Rapamycin is an antibiotic inhibiting mTOR. Different analogs of
      rapamycin are developed or being developed in antitumoral therapy, in which
      temsirolimus, everolimus and deforolimus, demonstrated antitumoral activity in
      renal cancer and mantle cell lymphoma, and many clinical trials are in progress
      in other tumors. In the future, predictive factors of response need to be
      identified; patient selection and associations with chemotherapy or with other
      targeted therapies should be explored.

PMID- 21742594
TI  - How to manage hypersensitivity reactions to biological agents?
AB  - Biological agents induce cutaneous adverse drug reactions (CADR) different from
      those observed with xenobiotics. Type alpha is the cytokine release syndrome,
      type beta are hypersensitivity reactions and type gamma is a cytokine imbalance
      syndrome. Infusion-reactions, anaphylactoid reactions occur with various
      biological agents administered intravenously. In non-severe cases the infusion
      rate has to be reduced, in severe reactions, the treatment must be stopped and
      resuscitation carried out with corticosteroids and epinephrine. Reactions may be
      due to an alpha syndrome but a true allergy could be involved as demonstrated in
      some patients with IgE antibodies to the galactose-alpha-1,3-galactose portion of
      the cetuximab or anti infliximab-IgE. Some desensitisation protocols have been
      published. Non allergic itching and eczema-like lesions are frequent with
      epidermal growth factor receptor inhibitors. Rash or desquamation was observed in
      40% of cases with antiangiogenic agents, 90% of patients treated with imatinib
      have rashes, oedema or pruritus and a non-allergic periorbital oedema. Severe
      CADR, such as Stevens-Johnson syndrome, can be provoked. Delayed readings of
      intradermal tests could be of value in managing patients with a maculopapular
      rash due to interferon. Anaphylaxis attributed to omalizumab seems to be rare
      (0.2%) and skin rashes occur in 7% of cases. Anaphylactoid reactions occur in 1%
      of patients treated with natalizumab. In the case of anti-natalizumab antibody
      mediated reactions, treatment should be stopped. These allergic-like side effects
      of new biological agents must be known and reported to Pharmacovigilance agency
      networks.

PMID- 21742595
TI  - Up-regulation of CC chemokine ligand 20 and its receptor CCR6 in the lesional
      skin of early systemic sclerosis.
AB  - Mononuclear cell (MNC) infiltrate is one of the earliest pathological changes in
      systemic sclerosis (SSc) skin. However, little is known about the recruitment of
      these cells into skin lesions. Recently, the role of chemokines has been
      suggested in the pathogenesis of SSc. Here we studied the expressions and
      distributions of CC chemokine CCL20 and its receptor CCR6 in early SSc skin
      lesions and the difference in CCL20 expressions and ability to recruite MNCs of
      normal dermal fibroblast (NDF) and scleroderma dermal fibroblast (SSDF). We found
      that the expressions of CCL20 and its receptor CCR6 were obviously up-regulated
      in SSc in contrast to normal human skin. mRNA levels were significantly expressed
      in SSc lesional skins vs normal skin tissues. SSDF displayed increased
      constitutive expressions of CCL20 mRNA and protein. In addition, Th1 cytokines
      (TNF-alpha and IL-1beta) remarkably increased the expression of CCL20 in both NDF
      and SSDF in a dose- and time-dependent manner. Supernatants from SSDF showed
      stronger chemotactic activity to PBMCs than those from NDF. Thus our findings
      suggest that CCL20 released from cytokine-activated SSDF plays an important role
      in the induction of SSc by further recruiting more MNCs to the skin.

PMID- 21742596
TI  - Tinea incognito complicating Cushing's syndrome secondary to a bronchial
      carcinoid tumour.

PMID- 21742597
TI  - A misleading CD68 positive balloon cell nevus on the penis in a child.

PMID- 21742598
TI  - Dermoscopic and histopathological findings of epidermotropic metastatic malignant
      melanoma.

PMID- 21742599
TI  - Plasma levels of resistin and ghrelin before and after treatment in patients with
      hyperthyroidism.
AB  - OBJECTIVE: To investigate ghrelin and resistin concentrations in patients with
      hyperthyroidism before and after restoration to a euthyroid state and to
      correlate the 2 peptides with anthropometric and insulin resistance parameters.
      METHODS: The study included hyperthyroid patients and euthyroid healthy
      participants as a control group. Hyperthyroid patients were evaluated at the
      start of the study and after normalization of thyroid function with appropriate
      antithyroid drugs. Anthropometric parameters, insulin resistance parameters
      (fasting blood glucose, fasting insulin, and homeostasis model assessment-insulin
      resistance), thyroid function tests, and measurement of ghrelin and resistin were
      assessed in patients and control participants. RESULTS: The study included 40
      hyperthyroid patients (32 women and 8 men, aged 26-42 years) and 30 euthyroid
      healthy participants (20 women and 10 men, aged 25-43 years) as a control group.
      In hyperthyroid patients, serum resistin levels and insulin resistance parameters
      were higher and plasma ghrelin levels were lower than in control participants
      (P<.001), and all normalized after treatment. Ghrelin levels were correlated only
      with insulin resistance parameters, but no correlations with any anthropometric
      or laboratory data were found. Resistin levels did not correlate with any
      clinical or laboratory data of hyperthyroid patients. CONCLUSION: In hyperthyroid
      patients, resistin was increased and ghrelin was decreased, they were not related
      to anthropometric parameters, and they normalized after treatment of
      hyperthyroidism.

PMID- 21742602
TI  - Long-term corticosteroid replacement in patients with adrenal insufficiency and
      measuring patient experience.

PMID- 21742603
TI  - Bariatric surgery and the role of the clinical endocrinologist: 2011 update.
AB  - OBJECTIVE: To discuss the emerging roles of bariatric surgery and clinical
      endocrinology within the context of obesity and diabetes mellitus comprehensive
      care plans and cost-effective strategies. METHODS: Relevant literature is
      reviewed and clinical cases are presented. RESULTS: The global obesity epidemic
      poses many challenges to clinical endocrinologists and has fomented a coordinated
      effort among specialists to revolutionize management paradigms. Technologic
      innovation drives the need for accelerated learning and research efforts in
      bariatric surgery. The national shortage of physicians with expertise in
      nutritional medicine compounds the management problems for this expanding patient
      population. Certain issues merit continued attention and research, such as
      gastric banding for mild obesity, surgery for treatment of diabetes, sleeve
      gastrectomy, and nutritional and metabolic consequences. CONCLUSION: Clinical
      endocrinologists should have a central role in the perioperative decision-making
      for patients undergoing bariatric surgery.

PMID- 21742604
TI  - Calciphylaxis in a morbidly obese woman with rheumatoid arthritis presenting with
      severe weight loss and vitamin D deficiency.
AB  - OBJECTIVE: To present an unusual case of calciphylaxis in an obese patient with
      inactive rheumatoid arthritis and normal renal function. METHODS: We describe a
      46-year-old morbidly obese Caucasian woman who had previously weighed 200 kg and
      presented with painful leg ulcers following a rapid weight loss of 102 kg in 1
      year. RESULTS: The subject was admitted with a 6-week history of painful leg
      ulcers that progressed to her thighs. Vasculitis and active rheumatoid arthritis
      were excluded clinically and biochemically. A skin biopsy confirmed calciphylaxis
      in the context of normal renal function. Serum 25-hydroxyvitamin D was low at 14
      ng/mL (reference range, 20 to 200 ng/mL), with an elevated serum parathyroid
      hormone level of 241 pg/mL (reference range, 10 to 65 pg/mL), but normal serum
      calcium and phosphorus levels. The skin lesions persisted despite local wound
      care, daily hyperbaric oxygen, and parenteral sodium thiosulfate therapies. After
      normalizing the serum vitamin D level through oral supplementation, she responded
      well to pamidronate infusion with complete healing of the ulcers and regained 13%
      of her premorbid weight. CONCLUSION: This is the first case of calciphylaxis
      preceded by weight loss of greater than 100 kg in a patient with hypovitaminosis
      D who responded to pamidronate therapy.

PMID- 21742605
TI  - Clinical outcomes using long-term combination therapy with insulin glargine and
      exenatide in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To examine the long-term effects of combination insulin
      glargine/exenatide treatment on glycemic control. METHODS: We conducted a 24
      month retrospective US chart review of patients with inadequately controlled type
      2 diabetes (T2DM) and hemoglobin A1c (A1C) levels >7.0% for whom glargine and
      exenatide were coprescribed in differing order (glargine added after exenatide
      [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]).
      Treatment order groups were combined to form a pooled treatment group. Changes
      from baseline in A1C, patients with A1C <=7.0%, body weight, glargine/exenatide
      daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated.
      RESULTS: Treatment groups were similar at baseline; however, patients in the
      glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had
      longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3).
      Overall, baseline A1C was 8.8 +/- 1.3% and weight was 109.5 +/- 25.3 kg.
      Significant A1C reductions emerged at month 6 and persisted throughout 24 months
      (vs baseline) in both treatment groups (pooled: -0.7 +/- 1.6; P<.001), and 33.0%
      of patients achieved an A1C level <=7.0%. After 24 months of exenatide/glargine,
      body weight remained unchanged (0.7 +/- 8.3 kg; P = .640). With
      glargine/exenatide, body weight decreased (-2.5 +/- 6.7 kg; P = .001). At month
      24, daily glargine dose was 0.40 +/- 0.23 units/kg for the exenatide/glargine
      group and 0.47 +/- 0.30 units/kg for the glargine/exenatide group. Hypoglycemia
      frequency was similar in both treatment groups. CONCLUSIONS: Regardless of
      treatment order, long-term combined therapy with glargine and exenatide for up to
      24 months in patients with inadequately controlled T2DM suggests reduction of A1C
      without significant weight gain or increased hypoglycemia risk.

PMID- 21742606
TI  - Thyroid-related factors that influence preoperative localization of parathyroid
      adenomas.
AB  - OBJECTIVE: To evaluate the effect that thyroid-related factors have on the
      preoperative localization of parathyroid adenomas. METHODS: This retrospective
      study included adult patients who were referred for further evaluation of primary
      hyperparathyroidism between December 2005 and October 2009 at a teaching and
      research hospital in Turkey. High-frequency ultrasonography and sestamibi
      scintigraphy (MIBI) were performed in all patients. Surgical procedure involved
      focal or bilateral exploration on the basis of concordant or discordant imaging
      studies. Selection of patients for minimally invasive parathyroidectomy was made
      based on the presence or absence of a single parathyroid adenoma detected by both
      ultrasonography and MIBI scan. Patients with negative or discordant imaging
      studies and a concomitant thyroid nodule underwent bilateral neck exploration.
      RESULTS: Two hundred and forty-eight patients with primary hyperparathyroidism
      who underwent parathyroidectomy were included in the study. Parathyroid gland
      abnormalities were successfully detected preoperatively by ultrasonography in 231
      patients and by MIBI scan in 152 patients. When used together, ultrasonography
      and MIBI scan were unsuccessful in detecting an abnormality in 11 cases. MIBI
      scan visualized a lesion in 6 cases that remained undiagnosed by ultrasonography.
      Fifty-six of 85 patients with lesions detected by ultrasonography, but not by
      MIBI scan, had thyroid nodules. The frequency of thyroid nodules was higher in
      the 96 patients in whom a MIBI scan could visualize a parathyroid lesion than in
      the 152 patients in whom MIBI scan was successful (P = .004). No difference was
      observed regarding ipsilateral thyroid lobe involvement or nodule volume.
      Parathyroid adenomas were significantly smaller in patients with negative MIBI
      scans (P<.001). CONCLUSION: Our results suggest that ultrasonography is more
      sensitive than MIBI scan in the detection of parathyroid adenomas, particularly
      in the presence of small parathyroid adenomas or other thyroid related-factors.

PMID- 21742607
TI  - Metformin and improvement of the hepatic insulin resistance index independent of
      anthropometric changes.
AB  - OBJECTIVE: To determine the change in the hepatic insulin resistance index (HIRI)
      after metformin treatment. METHODS: In this retrospective cohort study, Mexican
      mestizo patients with a body mass index (BMI) of 25 kg/m(2) or greater were
      evaluated. Participants were classified into 2 groups: patients who received
      metformin and patients who did not. Both groups were followed up for a median of
      6 months (range, 4-10 months). The HIRI was calculated at baseline and at follow
      up in both groups. We evaluated the independent effect of metformin on HIRI after
      adjustment for the difference in basal and final values (DELTA) of BMI, waist
      circumference, glucose, and insulin. RESULTS: A total of 71 patients were
      enrolled (51 [72%] female). Forty-one patients received metformin and 30 patients
      did not. Mean age was 36.3 +/- 12.2 years and mean BMI was 42.2 +/- 10.7 kg/m(2).
      After metformin treatment, HIRI significantly decreased from 38 +/- 10.7 to 34.7
      +/- 9.5 (P = .03). In contrast, the control group had a nonsignificant increase
      in HIRI (37.6 +/- 11.7 to 40.0 +/- 14.0, P = .22). Weight significantly decreased
      in both groups (group 1: 114.6 +/- 33.8 kg to 107.6 +/- 28.9 kg, P<.01; group 2:
      104.8 +/- 28.5 kg to 98.9 +/- 26.0 kg, P<.01). After BMI adjustment, the total
      metformin dosage correlated negatively with HIRI (r = -0.36, P = .03). Using a
      linear regression model (F = 6.0, r2 = 0.37, P = .002) adjusted for DELTA BMI and
      DELTA waist circumference, the administration of metformin resulted in
      independent improvement in the HIRI level (standardized beta = -0.29, t = -2.0, P
      = .04). CONCLUSIONS: Metformin improves HIRI independently of anthropometric
      changes. In persons with elevated HIRI levels, metformin may be considered among
      the treatment options.

PMID- 21742608
TI  - Functional consequences of succinate dehydrogenase mutations.
AB  - To explore the genotype-phenotype correlation among the different forms of
      hereditary paraganglioma. METHODS: We reviewed the pertinent literature on
      hereditary paragangliomas, which showed the established classification of types
      1, 2, 3, and 4 paraganglioma syndrome (PGL1, PGL2, PGL3, and PGL4, respectively).
      Germline mutations of succinate dehydrogenase confer susceptibilities as follows:
      SDHD confers susceptibility to PGL1 syndrome, SDHAF2 to PGL2 syndrome, SDHC to
      PGL3 syndrome, and SDHB to PGL4 syndrome. Recently, SDHA mutations have been
      identified in patients with parasympathetic paraganglioma. The 4 paraganglioma
      syndromes differ in terms of risk of malignancy, secretory activity, and tumor
      location. RESULTS: Little information is available on the biochemical and
      functional modifications induced by gene mutations in these tumors. Recent
      studies provide in vitro and in vivo evidence that succinate, fumarate, or both,
      which accumulate as a result of succinate dehydrogenase inhibition, lead to the
      stabilization and activation of hypoxia-inducible factor-1alpha, which in turn
      activates cell proliferation and angiogenesis. CONCLUSION: Paraganglia tumors
      (gross phenotype) are attributable to impairment of the mitochondrial complex II,
      type of gene mutated, type and position of the mutation, and type of second hit
      (other genes?) and are the determinants of the clinical phenotype. The
      relationship among various mutations, a different activity of the mitochondrial
      complex II, and the clinical phenotype are far from being established.

PMID- 21742609
TI  - The glucocorticoid receptor and its expression in the anterior pituitary and the
      adrenal cortex: a source of variation in hypothalamic-pituitary-adrenal axis
      function; implications for pituitary and adrenal tumors.
AB  - OBJECTIVE: To review the expression of the glucocorticoid receptor (GR) in
      anterior pituitary and adrenocortical cells and tumors derived from these tissues
      as well as factors that may influence its expression. METHODS: We present an
      overview of the relevant literature, with a focus on data generated from our
      studies. RESULTS: The expression of the GR is an essential element of the
      negative feedback that closes the loop formed by corticotropin-releasing hormone,
      adrenocorticotropic hormone, and cortisol in the context of the hypothalamic
      pituitary-adrenal (HPA) axis. Although the GR expression in anterior pituitary
      cells-and in particular the corticotrophs-was first demonstrated several years
      ago, it was not known until relatively recently where, by what cells, and in what
      form the GR is expressed in the adrenal cortex. The variability in the expression
      of the GR in pituitary and adrenocortical cells may underlie the substantial
      differences in HPA axis function across individuals, especially when testing for
      tumors associated with hypercortisolemia. This expression is influenced by a
      multitude of tissue-specific factors, which may explain why it is so difficult to
      interpret (or reproduce) studies that are based on GR functional polymorphisms on
      different cohorts of patients or even different sets of laboratory animals.
      CONCLUSION: This review highlights the variability in expression and function of
      the GR in pituitary and adrenocortical cells as one of the reasons for the
      appreciable differences in HPA axis function across individuals. Particular
      attention was paid to interactions that may affect the interpretation of
      diagnostic testing of the HPA axis in patients with pituitary adenomas (Cushing
      disease) or adrenocortical tumors (Cushing syndrome).

PMID- 21742610
TI  - Performance of plasma fractionated free metanephrines by enzyme immunoassay in
      the diagnosis of pheochromocytoma and paraganglioma.
AB  - OBJECTIVE: To study the performance of measuring plasma fractionated free
      metanephrines by enzyme immunoassay (EIA) in the diagnosis of pheochromocytoma
      and catecholamine-secreting paraganglioma. METHODS: Consecutive patients
      attending the endocrine clinic at King Edward Memorial Hospital, Mumbai, India,
      for suspicion of catecholamine-secreting tumors were included. Plasma
      fractionated free metanephrines were measured by EIA, and computed tomography of
      the neck, chest, abdomen, and pelvis was performed. Those with tumor identified
      by imaging underwent 131I m-iodobenzylguanidine scintigraphy. All patients with
      adrenal masses larger than 3 cm and patients with secretory tumors, irrespective
      of their size, underwent tumor excision. The rest were followed up for 6 to 12
      months. RESULTS: One hundred patients with a clinical suspicion of
      pheochromocytoma or paraganglioma were included. Plasma free normetanephrine
      alone had a sensitivity of 94.1% (cutoff: 180 ng/mL), while plasma free
      metanephrine had a sensitivity of 14.7% (cutoff: 90 pg/mL). Both had 96.9%
      specificity. When combined (either test positive), the sensitivity was 94.1% with
      a specificity of 93.75%. Thirty-four patients had a histopathologically proven
      pheochromocytoma or paraganglioma. It was concluded that 66 patients did not
      harbor a pheochromocytoma or catecholamine-secreting paraganglioma. CONCLUSION:
      Plasma fractionated free metanephrines measured by EIA have good sensitivity and
      specificity in the diagnosis of pheochromocytoma and catecholamine-secreting
      paraganglioma.

PMID- 21742611
TI  - Visual vignette. What is the diagnosis? Insulin-secreting tumor.

PMID- 21742612
TI  - Life-threatening hyponatremia following a low-iodine diet: a case report and
      review of all reported cases.
AB  - OBJECTIVE: To report a case of life-threatening hyponatremia as a complication of
      a 4-week long low-iodine diet and highlight the risk factors for this
      complication by reviewing all previously reported cases. METHODS: The clinical
      and biochemical data from the study patient are presented and the pertinent
      literature is reviewed. A risk analysis for this complication is highlighted.
      RESULTS: A 66-year-old Vietnamese woman had a total thyroidectomy and bilateral
      neck lymph node dissection for papillary thyroid carcinoma. A whole body
      radioiodine scan demonstrated 2 foci of activity in the anterior neck. The
      patient received recombinant human thyrotropin (rhTSH) and was admitted for
      radioiodine therapy. She had strictly adhered to a low-iodine diet for 4 weeks in
      preparation for ablation. The patient was on a thiazide diuretic for her
      hypertension, which was discontinued on admission. On admission, the patient
      started feeling light-headed, dizzy, and nauseated. Blood tests revealed a
      critical serum sodium concentration of 107 mEq/L. Further investigations
      confirmed hypotonic hyponatremia, which had developed despite being euthyroid
      after receiving rhTSH. The patient was managed accordingly and made a full
      recovery. CONCLUSIONS: This case, in addition to the reviewed cases, emphasizes
      the importance of preventing and managing this rare but relatively dangerous
      complication. Based on an analysis of the reviewed cases, the risk factors for
      developing this complication are a prolonged low-iodine diet, the elimination of
      salt from the diet, and the use of thiazide diuretics. All patients in the
      reported cases were older than 65 years of age.

PMID- 21742613
TI  - U500 regular insulin use in insulin-resistant type 2 diabetic veteran patients.
AB  - OBJECTIVE: To evaluate the use of U500 regular insulin therapy in insulin
      resistant patients with type 2 diabetes mellitus who were previously treated with
      high-dosage U100 insulin regimens. METHODS: At a large Veterans Affairs medical
      center, a retrospective chart review was performed of all patients whose U100
      insulin regimens were converted to U500 regular insulin regimens using a protocol
      to ensure patient safety. Patients were followed up for longer than 6 months.
      Data reviewed included total daily dosage of insulin before and after regimen
      conversion and changes in hemoglobin A1c, body weight, lipids, and episodes of
      severe hypoglycemia. RESULTS: Fifty-three patients met inclusion criteria.
      Average hemoglobin A1c level on U100 insulin regimens was 9.1 +/- 1.7%, which
      decreased to 8.1 +/- 1.3% (P<.001) after an average of 20 months (range, 6-52
      months) on U500 insulin. The total daily insulin dosage at study end was not
      significantly greater on U500 (415 +/- 166 units/day) than on U100 insulin (391
      +/- 120 units/day) (P = .34). Body weight did not change significantly (134 +/-
      29 kg vs 136 +/- 30 kg, P = .18). There was a 20-mg/dL decrease in total
      cholesterol (P = .014). Triglyceride values decreased by 97 mg/dL (P = .005).
      Eight episodes of severe hypoglycemia were documented in patients treated with
      U500 insulin, but this was similar to the incidence in these same patients while
      treated with U100 insulin. CONCLUSION: We conclude that U500 insulin can be
      safely and effectively used in insulin-resistant patients with type 2 diabetes
      followed up at a large Veterans Affairs medical center using a protocol that
      ensures patients are thoroughly educated and carefully monitored.

PMID- 21742614
TI  - Predictors of osteodystrophy in patients with chronic nonalcoholic pancreatitis
      with or without diabetes.
AB  - OBJECTIVE: To study bone mineral content (BMC), bone mineral density (BMD),
      vitamin D status, and bone mineral variables in patients with chronic
      nonalcoholic pancreatitis and to determine the relationship between pancreatic
      dysfunction and these variables. METHODS: Thirty-one eligible nonalcoholic men
      with proven chronic pancreatitis and 35 male control subjects were studied.
      Biochemical data, variables of malabsorption, and BMD of the lumbar spine were
      evaluated. RESULTS: In patients with chronic pancreatitis, the mean body mass
      index (BMI) was 18.46 kg/m2 and the median 25-hydroxyvitamin D value was 15.5
      (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher
      proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35,
      9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an
      inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients
      with chronic pancreatitis and steatorrhea. There was no significant correlation
      between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with
      steatorrhea had a significantly lower BMC than did those without steatorrhea, and
      this difference could not be accounted for by differences in BMI, presence of
      diabetes, or hypovitaminosis D. CONCLUSION: Pancreatic osteodystrophy is a novel
      entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with
      chronic pancreatitis. The inverse correlation between stool fat and BMC in
      patients with chronic pancreatitis, the strong positive correlation between BMI
      and BMC, and the lack of difference in BMC between subjects with vitamin D
      sufficiency and those with vitamin D deficiency suggest that long-standing
      malabsorption with attendant chronic undernutrition is the major factor
      contributing to the changes in BMC.

PMID- 21742615
TI  - Diabetes insipidus associated with hemophagocytic lymphohistiocytosis: first case
      report.
AB  - OBJECTIVE: To report the first case of central diabetes insipidus associated with
      hemophagocytic lympho-histiocytosis. METHODS: We describe the clinical course of
      a 75-year-old woman who developed febrile illness 1 month after receiving the
      H1N1 influenza vaccination. Shortly thereafter, she developed central diabetes
      insipidus, which responded to treatment with intranasal desmopressin acetate. She
      was then hospitalized with another febrile illness and diagnosed with
      hemophagocytic lymphohistiocytosis. RESULTS: Magnetic resonance imaging of the
      pituitary gland was significant for plaquelike meningeal enhancement and
      thickening surrounding the infundibulum, which has been previously reported as a
      manifestation of histiocytosis. CONCLUSION: We believe this is the first case of
      central diabetes insipidus associated with hemophagocytic lymphohistiocytosis.

PMID- 21742616
TI  - Cardiac and coronary CT comprehensive imaging approach in the assessment of
      coronary heart disease.
AB  - Cardiac CT is a rapidly advancing technology. Non-invasive CT coronary
      angiography is an established technique for assessing coronary heart disease with
      accuracy similar to invasive coronary angiography. CT myocardial perfusion
      imaging can now identify perfusion defects in animal models and humans. MRI is
      the current 'gold standard' for the assessment of myocardial viability, but it is
      now also possible to assess delayed enhancement by CT. This has led to the
      possibility of a 'one-stop shop' for cardiovascular imaging that would provide
      information on anatomy, function, perfusion and viability in one rapid diagnostic
      test at a radiation dose equivalent to contemporary nuclear medicine imaging.
      This review discusses the current status of 'one-stop shop' cardiac CT
      assessment, clinical utility and directions for future research.

PMID- 21742617
TI  - The translational science of Marfan syndrome.
AB  - Marfan syndrome has changed over the last few years: new diagnostic criteria have
      been proposed, new clinical entities recognised and life expectancy increased.
      The role of fibrillin 1, which was initially thought to be mainly structural, has
      been shown to also be functional. The altered transforming growth factor beta
      pathway is better understood, the importance of epigenetic factors has been
      demonstrated and recent data suggest that many of the observations made in Marfan
      syndrome can actually be made in thoracic aortic aneurysm from diverse
      aetiologies. Besides transforming growth factor beta, the role of
      metalloproteinase, the fibrinolytic/coagulation system, is being suggested in the
      progression of the disease. A relationship between the type of fibrillin 1 (FBN1)
      gene mutation and the mechanism for the disease (haplo-insufficiency vs negative
      dominance), as well as some genotype/phenotype correlations, has been observed,
      although the main challenge of recognising gene modifiers has yet to explain
      tremendous variability despite similar mutation. This progress has led to new
      hopes for tomorrow's therapies, some of which are being tested in clinics,
      whereas others are still in the field of animal models. Here we review some of
      the new data obtained in the understanding of the pathophysiology and genetics of
      this disease.

PMID- 21742618
TI  - New P2Y12 inhibitors.

PMID- 21742619
TI  - Pharmacogenetics of antiplatelet therapy: ready for clinical application?

PMID- 21742620
TI  - A highway for war and peace: the secretory pathway in plant-microbe interactions.
AB  - Secretion of proteins and other molecules is the primary means by which a cell
      interacts with its surroundings. The overall organization of the secretory system
      is remarkably conserved among eukaryotes, and many of the components have been
      investigated in detail in animal models. Plant cells, because of their sessile
      lifestyle, are uniquely reliant on the secretory pathway to respond to changes in
      their environments, either abiotic, such as the absence of nutrients, or biotic,
      such as the presence of predators or pathogens. In particular, most plant
      pathogens are extracellular, which demands a robust and efficient host secretory
      system directed at the site of attack. Here, we present a summary of recent
      advances in our understanding of the molecular details of the secretory pathway
      during plant-microbe interactions. Secretion is required not only for the
      delivery of antimicrobial molecules, but also for the biogenesis of cell surface
      sensors to detect microbes. The deposition of extracellular material is important
      in the defense against classical bacterial pathogens as well as in the so-called
      'non-host' resistance. Finally, boosting the protein secretion capacity is vital
      for avoiding infection as well as for achieving symbiosis, even though in the
      latter case, the microbes are engulfed in intracellular compartments. The
      emerging evidence indicates that secretion provides an essential interface
      between plant hosts and their associated microbial partners.

PMID- 21742623
TI  - Get your work noticed: how authors can help readers to find annals papers online.

PMID- 21742624
TI  - Applying quality criteria to exposure in asbestos epidemiology increases the
      estimated risk.
AB  - Mesothelioma deaths due to environmental exposure to asbestos in The Netherlands
      led to parliamentary concern that exposure guidelines were not strict enough. The
      Health Council of the Netherlands was asked for advice. Its report has recently
      been published. The question of quality of the exposure estimates was studied
      more systematically than in previous asbestos meta-analyses. Five criteria of
      quality of exposure information were applied, and cohort studies that failed to
      meet these were excluded. For lung cancer, this decreased the number of cohorts
      included from 19 to 3 and increased the risk estimate 3- to 6-fold, with the
      requirements for good historical data on exposure and job history having the
      largest effects. It also suggested that the apparent differences in lung cancer
      potency between amphiboles and chrysotile may be produced by lower quality
      studies. A similar pattern was seen for mesothelioma. As a result, the Health
      Council has proposed that the occupational exposure limit be reduced from 10 000
      fibres m(-3) (all types) to 250 f m(-3) (amphiboles), 1300 f m(-3) (mixed
      fibres), and 2000 f m(-3) (chrysotile). The process illustrates the importance of
      evaluating quality of exposure in epidemiology since poor quality of exposure
      data will lead to underestimated risk.

PMID- 21742625
TI  - The risk of asbestos exposure in South African diamond mine workers.
AB  - OBJECTIVES: Asbestos is associated with South African diamond mines due to the
      nature of kimberlite and the location of the diamond mines in relation to
      asbestos deposits. Very little is known about the health risks in the diamond
      mining industry. The objective of this study was to explore the possibility of
      asbestos exposure during the process of diamond mining. METHODS: Scanning
      electron microscopy and energy-dispersive X-ray spectroscopy analysis were used
      to identify asbestos fibres in the lungs of diamond mine workers who had an
      autopsy for compensation purposes and in the tailings and soils from three South
      African diamond mines located close to asbestos deposits. The asbestos lung fibre
      burdens were calculated. We also documented asbestos-related pathological
      findings in diamond mine workers at autopsy. RESULTS: Tremolite-actinolite
      asbestos fibres were identified in the lungs of five men working on diamond
      mines. Tremolite-actinolite and/or chrysotile asbestos were present in the mine
      tailings of all three mines. Mesothelioma, asbestosis, and/or pleural plaques
      were diagnosed in six diamond mine workers at autopsy. CONCLUSIONS: These
      findings indicate that diamond mine workers are at risk of asbestos exposure and,
      thus, of developing asbestos-related diseases. South Africa is a mineral-rich
      country and, when mining one commodity, it is likely that other minerals,
      including asbestos, will be accidentally mined. Even at low concentrations,
      asbestos has the potential to cause disease, and mining companies should be aware
      of the health risk of accidentally mining it. Recording of comprehensive work
      histories should be mandatory to enable the risk to be quantified in future
      studies.

PMID- 21742626
TI  - Exposure to flame retardants in electronics recycling sites.
AB  - Waste electrical and electronic equipment (WEEE) contains various hazardous
      substances such as flame retardants (FRs). Inhalation exposures to many FRs
      simultaneously among WEEE recycling site workers have been little studied
      previously. The breathing zone airborne concentrations of five brominated FR
      compounds tetrabromobisphenol-A (TBBP-A), decabromodiphenylethane (DBDPE),
      hexabromocyclododecane, 1,2-bis(2,4,6-tribromophenoxy)ethane, hexabromobenzene,
      and one chlorinated FR (Dechlorane Plus(r)) were measured at four electronics
      recycling sites in two consecutive years. In addition, concentrations of
      polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls were
      measured. The three most abundant FRs in personal air samples were PBDEs
      (comprising mostly of deca-BDE), TBBP-A, and DBDPE, with mean concentrations
      ranging from 21 to 2320 ng m(-)(3), from 8.7 to 430 ng m(-3), and from 3.5 to 360
      ng m(-3), respectively. At two of the sites, the emission control actions (such
      as improvements in ventilation and its maintenance and changes in cleaning
      habits) proved successful, the mean levels of FRs in personal samples being 10-68
      and 14-79% of those from the previous year or alternatively below the limit of
      quantification. At the two remaining sites, the reductions in FR exposures were
      less consistent. The concentrations reported may pose a health hazard to the
      workers, although evaluation of the association between FR exposure and adverse
      health effects is hampered by lacking occupational exposure limits. Therefore,
      the exposures should be minimized by adequate control measures and maintaining
      good occupational hygiene practice.

PMID- 21742627
TI  - Comparison of pressure drop and filtration efficiency of particulate respirators
      using welding fumes and sodium chloride.
AB  - Respirators are used to help reduce exposure to a variety of contaminants in
      workplaces. Test aerosols used for certification of particulate respirators (PRs)
      include sodium chloride (NaCl), dioctyl phthalate, and paraffin oil. These
      aerosols are generally assumed to be worst case surrogates for aerosols found in
      the workplace. No data have been published to date on the performance of PRs with
      welding fumes, a hazardous aerosol that exists in real workplace settings. The
      aim of this study was to compare the performance of respirators and filters
      against a NaCl aerosol and a welding fume aerosol and determine whether or not a
      correlation between the two could be made. Fifteen commercial PRs and filters
      (seven filtering facepiece, two replaceable single-type filters, and six
      replaceable dual-type filters) were chosen for investigation. Four of the
      filtering facepiece respirators, one of the single-type filters, and all of the
      dual-type filters contained carbon to help reduce exposure to ozone and other
      vapors generated during the welding process. For the NaCl test, a modified
      National Institute for Occupational Safety and Health protocol was adopted for
      use with the TSI Model 8130 automated filter tester. For the welding fume test,
      welding fumes from mild steel flux-cored arcs were generated and measured with a
      SIBATA filter tester (AP-634A, Japan) and a manometer in the upstream and
      downstream sections of the test chamber. Size distributions of the two aerosols
      were measured using a scanning mobility particle sizer. Penetration and pressure
      drop were measured over a period of aerosol loading onto the respirator or
      filter. Photos and scanning electron microscope images of clean and exposed
      respirators were taken. The count median diameter (CMD) and mass median diameter
      (MMD) for the NaCl aerosol were smaller than the welding fumes (CMD: 74 versus
      216 nm; MMD: 198 versus 528 nm, respectively). Initial penetration and peak
      penetration were higher with the NaCl aerosol. However, pressure drop increased
      much more rapidly in the welding fume test than the NaCl aerosol test. The data
      and images clearly show differences in performance trends between respirator
      models. Therefore, general correlations between NaCl and weld fume data could not
      be made. These findings suggest that respirators certified with a surrogate test
      aerosol such as NaCl are appropriate for filtering welding fume (based on
      penetration). However, some respirators may have a more rapid increase in
      pressure drop from the welding fume accumulating on the filter. Therefore,
      welders will need to choose which models are easier to breathe through for the
      duration of their use and replace respirators or filters according to the user
      instructions and local regulations.

PMID- 21742628
TI  - Development of a method for the determination of naphthalene and phenanthrene in
      workplace air using diffusive sampling and thermal desorption GC-MS analysis.
AB  - Diffusive sampling methods have been validated for the determination of
      naphthalene and phenanthrene in workplace air. The diffusive sampler tested was
      the Perkin Elmer ATD tube, and the analysis was performed with thermal
      desorption, gas chromatography, and mass spectrometric detection. The sampling
      methods were validated in controlled test atmospheres, mainly according to the
      protocol proposed in the European standard EN 838. For the determination of
      naphthalene, the diffusive sampling rate was 0.41 ml min(-1) with a coefficient
      of variation (CV) of 19%. The mean sampling rate for phenanthrene was 0.49 ml
      min(-1) with a CV of 21%. Field tests confirmed the naphthalene results but could
      not be used to confirm the phenanthrene results. The method is not recommended
      for phenanthrene sampling unless the method has been tested in the specific
      environment and the results confirm the laboratory tests.

PMID- 21742632
TI  - Introduction: embryonic stem cell research, abortion, euthanasia, and the
      plurality of moralities in bioethics.

PMID- 21742633
TI  - A second infA plastid gene point mutation shows a compensatory effect on the
      expression of the cytoplasmic line 2 (CL2) syndrome in barley.
AB  - The IF1 protein is one of the factors controlling translation initiation in
      bacteria. This protein is encoded by the infA gene, which, in several higher
      plants, is located in the plastome. Cytoplasmic Line 2 (CL2), an alboviridis
      barley mutant, was the first to be proposed as an infA gene mutation (T 157 C) in
      higher plants. This mutant was isolated from a chloroplast mutator genotype
      (cpm/cpm) and was made genetically stable by backcrosses with a wild-type nuclear
      genotype. In the present work, genetically stable CL2 plants were backcrossed as
      females by cpm/cpm plants in order to regain the mutator activity. Interestingly,
      a seedling carrying a first leaf blade with a darker green stripe on a typical
      CL2-mutant background was observed in the F(4) generation. The T 157 C transition
      was confirmed in tissues from the CL2 background, whereas a second transition (A
      178 G) was also found in the darker stripe. Two clearly different levels of CL2
      syndrome were observed in the seedlings of the F(5) and F(6) progenies. Those of
      the greener group carried both transitions. These results suggest a compensatory
      effect of the second mutation and support the involvement of the infA plastid
      gene in CL2 syndrome, confirming CL2 as the first mutant of this gene reported in
      higher plants.

PMID- 21742634
TI  - PREDA: an R-package to identify regional variations in genomic data.
AB  - SUMMARY: Chromosomal patterns of genomic signals represent molecular fingerprints
      that may reveal how the local structural organization of a genome impacts the
      functional control mechanisms. Thus, the integrative analysis of multiple sources
      of genomic data and information deepens the resolution and enhances the
      interpretation of stand-alone high-throughput data. In this note, we present
      PREDA (Position RElated Data Analysis), an R package for detecting regional
      variations in genomics data. PREDA identifies relevant chromosomal patterns in
      high-throughput data using a smoothing approach that accounts for distance and
      density variability of genomics features. Custom-designed data structures allow
      efficiently managing diverse signals in different genomes. A variety of smoothing
      functions and statistics empower flexible and robust workflows. The modularity of
      package design allows an easy deployment of custom analytical pipelines. Tabular
      and graphical representations facilitate downstream biological interpretation of
      results. AVAILABILITY: PREDA is available in Bioconductor and at
      http://www.xlab.unimo.it/PREDA. CONTACT: silvio.bicciato@unimore.it SUPPLEMENTARY
      INFORMATION: Supplementary information is available at Bioinformatics online.

PMID- 21742635
TI  - DivBayes and SubT: exploring species diversification using Bayesian statistics.
AB  - SUMMARY: DivBayes is a program to estimate diversification rates from species
      richness and ages of a set of clades. SubT estimates diversification rates from
      node heights within a clade. Both programs implement Bayesian statistics and
      provide the ability to account for uncertainty in the ages of taxa in the
      underlying data, an improvement over more commonly used maximum likelihood
      methods. AVAILABILITY: DivBayes and SubT are released as C++ source code under
      the GNU GPL v. 3 software license in Supplementary information 1 and 2,
      respectively, and at http://web.utk.edu/~kryberg/. They have been successfully
      compiled on various Linux, MacOS X and Windows systems. CONTACT: kryberg@utk.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 21742636
TI  - Biologically inspired EM image alignment and neural reconstruction.
AB  - MOTIVATION: Three-dimensional reconstruction of consecutive serial-section
      transmission electron microscopy (ssTEM) images of neural tissue currently
      requires many hours of manual tracing and annotation. Several computational
      techniques have already been applied to ssTEM images to facilitate 3D
      reconstruction and ease this burden. RESULTS: Here, we present an alternative
      computational approach for ssTEM image analysis. We have used biologically
      inspired receptive fields as a basis for a ridge detection algorithm to identify
      cell membranes, synaptic contacts and mitochondria. Detected line segments are
      used to improve alignment between consecutive images and we have joined small
      segments of membrane into cell surfaces using a dynamic programming algorithm
      similar to the Needleman-Wunsch and Smith-Waterman DNA sequence alignment
      procedures. A shortest path-based approach has been used to close edges and
      achieve image segmentation. Partial reconstructions were automatically generated
      and used as a basis for semi-automatic reconstruction of neural tissue. The
      accuracy of partial reconstructions was evaluated and 96% of membrane could be
      identified at the cost of 13% false positive detections. AVAILABILITY: An open
      source reference implementation is available in the Supplementary information.
      CONTACT: seymour.kb@ed.ac.uk; douglas.armstrong@ed.ac.uk SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 21742637
TI  - Higher dynamic medial knee load predicts greater cartilage loss over 12 months in
      medial knee osteoarthritis.
AB  - OBJECTIVE: Mechanical factors, in particular increased medial knee joint load,
      are believed to be important in the structural progression of knee
      osteoarthritis. This study evaluated the relationship of medial knee load during
      walking to indices of structural disease progression, measured on MRI, in people
      with medial knee osteoarthritis. METHODS: A longitudinal cohort design utilising
      a subset of participants (n=144, 72%) enrolled in a randomised controlled trial
      of lateral wedge insoles was employed. Medial knee load parameters including the
      peak knee adduction moment (KAM) and the KAM impulse were measured at baseline
      using three-dimensional gait analysis during walking. MRI at baseline and at 12
      months was used to assess structural indices. Multiple regression with adjustment
      for covariates assessed the relationship between medial knee load parameters and
      the annual change in medial tibial cartilage volume. Binary logistic regression
      was used for the dichotomous variables of progression of medial tibiofemoral
      cartilage defects and bone marrow lesions (BML). RESULTS: A higher KAM impulse,
      but not peak KAM, at baseline was independently associated with greater loss of
      medial tibial cartilage volume over 12 months (beta=29.9, 95% CI 6.3 to 53.5,
      p=0.01). No significant relationships were seen between medial knee load
      parameters and the progression of medial tibiofemoral cartilage defects or BML.
      CONCLUSION: This study suggests knee loading, in particular the KAM impulse, may
      be a risk factor for loss of medial tibial cartilage volume. As knee load is
      modifiable, load-modifying treatments may potentially slow disease progression.

PMID- 21742638
TI  - Bone mineral density and joint cartilage: four clinical settings of a complex
      relationship in osteoarthritis.
AB  - Experimental and clinical data support the hypothesis that both high and low bone
      mineral density (BMD) conditions, including osteoporosis, may induce
      osteoarthritis. However, these conditions do not always predispose to
      osteoarthritis progression. Four clinical settings could arise from this
      relationship, and furthermore two phenotypes may be identified whether early
      osteoarthritis coexists with high or low BMD.

PMID- 21742639
TI  - Cytokine mRNA profiling identifies B cells as a major source of RANKL in
      rheumatoid arthritis.
AB  - OBJECTIVES: In rheumatoid arthritis (RA), a complex cytokine network drives
      chronic inflammation and joint destruction. So far, few attempts have been made
      to identify the cellular sources of individual cytokines systematically.
      Therefore, the primary objective of this study was systematically to assess the
      cytokine messenger RNA expression profiles in the five largest cell populations
      in the synovial fluid and peripheral blood of RA patients. To reflect the in vivo
      situation as closely as possible, the cells were neither cultured nor stimulated
      ex vivo. METHODS: Inflammatory cells from 12 RA patients were sorted into CD4 and
      CD8 T cells, B cells, macrophages and neutrophils. mRNA expression for 41
      cytokines was determined by real-time PCR using microfluidic cards. Receptor
      activator nuclear factor kappa B ligand (RANKL) (TNFSF11) expression by B cells
      was further confirmed by flow cytometry and by immunofluorescence staining of
      frozen sections of synovial tissue from patients with RA. RESULTS: The detection
      of cytokines characteristic for T cells and myeloid cells in the expected
      populations validated this methodology. Beyond the expected cytokine patterns,
      novel observations were made. Striking among these was the high expression of
      mRNA for RANKL in B cells from synovial fluid. This observation was validated at
      the protein level in synovial tissue and fluid. CONCLUSIONS: RANKL, the key
      cytokine driving bone destruction by osteoclast activation, is produced by
      synovial B cells in RA. This observation is of importance for our understanding
      of the role of B cells in RA and their therapeutic targeting.

PMID- 21742640
TI  - Osteophytes and joint space narrowing are independently associated with pain in
      finger joints in hand osteoarthritis.
AB  - OBJECTIVE: To study the associations between structural abnormalities on
      ultrasound (US) or conventional x-rays (CR) and pain in hand osteoarthritis
      (HOA). METHODS: In 55 consecutive patients with HOA (mean age 61 years, 86%
      women) fulfilling the American College of Rheumatology criteria, pain in 30
      separate hand joints was assessed upon palpation; osteophytes were assessed by US
      and CR and joint space narrowing (JSN) by CR. Associations between structural
      abnormalities and pain per joint were analysed using generalised estimated
      equations to account for patient effects and adjusted for age, sex, body mass
      index, US inflammatory features and other remaining structural abnormalities.
      RESULTS: In 1649 joints, 69% and 46% had osteophytes on US and CR, respectively
      and 47% had JSN. Osteophytes and JSN showed independent associations with pain
      per joint adjusted: OR for osteophytes: 4.8 (95% CI 3.1 to 7.5) for US and 4.1
      (95% CI 2.4 to 7.1) for CR; for JSN: 4.2 (95% CI 2.0 to 9.0). CONCLUSIONS:
      Osteophytes and JSN are independently associated with pain in individual HOA
      joints, taking into account patient effects.

PMID- 21742641
TI  - SIRT1 overexpression in the rheumatoid arthritis synovium contributes to
      proinflammatory cytokine production and apoptosis resistance.
AB  - OBJECTIVE: To analyse the expression of SIRT1 in synovial tissues and cells of
      patients with rheumatoid arthritis (RA) and to study the function of SIRT1 in
      inflammation and apoptosis in RA. METHODS: Levels of SIRT1 expression were
      analysed in synovial tissues and cells from patients with RA by real-time PCR and
      western blotting before and after stimulation with toll-like receptor ligands,
      tumour necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta).
      Immunohistochemistry was used to study the localisation of SIRT1. Fluorescence
      activated cell sorting analysis was performed to investigate the effect of SIRT1
      on apoptosis. Peripheral blood monocytes and rheumatoid arthritis synovial
      fibroblasts (RASFs) were transfected with wild-type or enzymatically inactive
      SIRT1 expression vectors or with siRNA targeting SIRT1. Cytokine analysis of IL
      6, IL-8 and TNFalpha were performed by ELISA to study the role of SIRT1 on
      proinflammatory mediators of RA. RESULTS: SIRT1 was found to be constitutively
      upregulated in synovial tissues and cells from patients with RA compared to
      osteoarthritis. TNFalpha stimulation of RASFs and monocytes resulted in further
      induced expression levels of SIRT1. Silencing of SIRT1 promoted apoptosis in
      RASFs, whereas SIRT1 overexpression protected cells from apoptosis. Inhibition of
      SIRT1 enzymatic activity by inhibitors, siRNA and overexpression of an
      enzymatically inactive form of SIRT1 reduced lipopolysaccharide-induced levels of
      TNFalpha in monocytes. Similarly, knockdown of SIRT1 resulted in a reduction of
      proinflammatory IL-6 and IL-8 in RASFs. CONCLUSION: The TNFalpha-induced
      overexpression of SIRT1 in RA synovial cells contributes to chronic inflammation
      by promoting proinflammatory cytokine production and inhibiting apoptosis.

PMID- 21742642
TI  - Memory predicts changes in depressive symptoms in older adults: a bidirectional
      longitudinal analysis.
AB  - OBJECTIVES: Although research indicates that depressive symptoms and memory
      performance are related in older adults, the temporal associations between these
      variables remain unclear. This study examined whether depressive symptoms
      predicted later memory change and whether memory predicted later change in
      depressive symptoms. METHODS: The sample consisted of more than 14,000 adults
      from the Health and Retirement Study, a biannual longitudinal study of health and
      retirement in Americans older than age 50 years. Measures of delayed recall and
      depressive symptoms served as the main study variables. We included age, sex,
      education, and history of vascular diseases as covariates. RESULTS: Using dynamic
      change models with latent difference scores, we found that memory performance
      predicted change in depressive symptoms 2 years later. Depressive symptoms did
      not predict later change in memory. The inclusion of vascular health variables
      diminished the size of the observed relationship, suggesting that biological
      processes may partially explain the effect of memory on depressive symptoms.
      IMPLICATIONS: Future research should explore both biological and psychological
      processes that may explain the association between worse memory performance and
      subsequent increases in depressive symptoms.

PMID- 21742643
TI  - Prevalence of asymmetric molar and canine relationship.
AB  - The purpose of this study was to investigate the prevalence and severity of
      occlusal asymmetries in the molar and canine regions in a large population-based
      sample of adolescent Kuwaitis. Using a stratified cluster sampling method, 1299
      Kuwaiti adolescents (674 boys mean age 13.3 years and 625 girls mean age 13.2
      years), representing approximately 6.7 per cent of that age stratum in the
      population, were examined clinically for sagittal molar and canine relationships,
      with a view to recording half and full-step asymmetries. In this sample, 1244
      subjects were examined clinically, while for the remaining 55, pre-treatment
      study models were assessed. All subjects were in the early permanent dentition
      stage. Descriptive statistical analyses were used to determine the proportion of
      different molar and canine asymmetries. Antero-posterior asymmetries were found
      to be a distinctive and common feature of the dental arches, with half-step
      outweighing full-step asymmetries both in the anterior and posterior regions. The
      total prevalence of an asymmetric molar or canine relationship was 29.7 and 41.4
      per cent, respectively, with more than 95 per cent falling in the mild category.
      Patient gender did not influence the prevalence or magnitude of asymmetry. The
      results showed a clinically significant prevalence of asymmetric molar and canine
      relationships, which were mainly in the category of half-step asymmetry. Class II
      half and full-step asymmetries were more prevalent than Class III asymmetries in
      the molar and canine regions.

PMID- 21742644
TI  - Solitary fibrous tumor of the vagina: a case report with review of the
      literature.
AB  - Solitary fibrous tumor, initially described in the pleura, is now known to occur
      in various extrathoracic sites. However, its occurrence in the female genital
      tract, especially the vagina, is extremely rare. The authors report here a case
      of a well-circumscribed vaginal spindle cell nodule in a 48-year-old woman with
      features consistent with solitary fibrous tumor. The diagnosis was established
      histologically by the varying pattern with hypocellular fibrous areas alternating
      with hypercellular areas and hemangiopericytoma-like areas and,
      immunohistochemically by the strong positive reaction for CD34 and Bcl2 with a
      negative reaction for all other spindle cell and epithelial markers. The
      differential diagnosis is discussed and a review of the literature is presented.

PMID- 21742645
TI  - Coexistence of renal epithelioid angiomyolipoma and clear cell carcinoma in
      patients without tuberous sclerosis.
AB  - Renal epithelioid angiomyolipoma (EAML) is a rare but distinct variant of
      angiomyolipoma, closely simulating renal cell carcinoma or sarcoma both
      clinically and histopathologically. This report presents an unusual case of
      unilateral simultaneous renal EAML and renal clear cell carcinoma. A 52-year-old
      man without any sign of tuberous sclerosis had a complaint of 6-month history of
      pain in left renal area and had macroscopic hematuria twice within the recent 1
      month. Computed tomography showed the presence of 2 masses in the upper and lower
      portion of the left kidney. The patient underwent left radical nephrectomy.
      Histological examination revealed the upper mass was composed of medium to large
      epithelioid cells with clear or eosinophilic cytoplasm and numerous giant
      multinucleated cells. Adult-appearing adipose tissue and coagulative necrosis
      could also be observed focally in the mass. Immunohistochemically, the tumor
      cells in the upper mass showed positive reactions to actin, HMB-45, Melan-A, and
      CD68 but negative reactions to pan-cytokeratin (pan-CK), epithelial membrane
      antigen, and CD10. However, the lower mass was composed of diffusely monomorphic
      clear cells with strongly immunoreactive for pan-CK, vimentin, and CD10, whereas
      without expression for HMB-45 and actin. The patient showed no evidence of
      recurrence or metastasis during 1-year postoperative following-up period. To the
      authors' knowledge, this is the first report of coincidental renal EAML and clear
      cell carcinoma in the same kidney. Unlike classic triphasic angiomyolipoma,
      adjuvant therapy after resection should be considered for renal EAML because of
      its malignant potential, more aggressive behavior and poor prognosis.

PMID- 21742646
TI  - Coexistence of primary gastric giant cell-rich leiomyosarcoma and
      gastrointestinal stromal tumor: report of a very rare combination and review of
      the literature.
AB  - Leiomyosarcoma is one of the most common types of soft tissue sarcoma, usually
      seen in deep soft tissues of the extremities and retroperitoneum. Leiomyosarcoma
      primarily involving the gastrointestinal tract is uncommon. This report presents
      a rare case of primary gastric giant cell-rich leiomyosarcoma associated with a
      gastrointestinal stromal tumor of the stomach in a 51-year-old man. The patient
      was alive with no evidence of recurrence 10 months later. To the authors'
      knowledge, this association has not been previously reported.

PMID- 21742647
TI  - Schwannoma of the tongue with a happy ending.

PMID- 21742648
TI  - Cohort study: travel time from home to hospital and adverse perinatal outcomes in
      women at term in The Netherlands.

PMID- 21742649
TI  - An intervention to improve compliance with guidelines for prevention of venous
      thromboembolism improves the proportion of hospitalised patients receiving
      appropriate prophylaxis.

PMID- 21742650
TI  - Behavior change techniques used in group-based behavioral support by the English
      stop-smoking services and preliminary assessment of association with short-term
      quit outcomes.
AB  - OBJECTIVE: To develop a reliable coding scheme for components of group-based
      behavioral support for smoking cessation, to establish the frequency of inclusion
      in English Stop-Smoking Service (SSS) treatment manuals of specific components,
      and to investigate the associations between inclusion of behavior change
      techniques (BCTs) and service success rates. METHODS: A taxonomy of BCTs specific
      to group-based behavioral support was developed and reliability of use assessed.
      All English SSSs (n = 145) were contacted to request their group-support
      treatment manuals. BCTs included in the manuals were identified using this
      taxonomy. Associations between inclusion of specific BCTs and short-term (4-week)
      self-reported quit outcomes were assessed. RESULTS: Fourteen group-support BCTs
      were identified with >90% agreement between coders. One hundred and seven
      services responded to the request for group-support manuals of which 30 had
      suitable documents. On average, 7 BCTs were included in each manual. Two were
      positively associated with 4-week quit rates: "communicate group member
      identities" and a "betting game" (a financial deposit that is lost if a stop
      smoking "buddy" relapses). CONCLUSION: It is possible to reliably code group
      specific BCTs for smoking cessation. Fourteen such techniques are present in
      guideline documents of which 2 appear to be associated with higher short-term
      self-reported quit rates when included in treatment manuals of English SSSs.

PMID- 21742651
TI  - Ethnoracial differences in emergency department patients' tobacco use.
AB  - INTRODUCTION: This study examined ethnoracial differences in lifetime and recent
      tobacco use and related problems in a large convenience sample of Latino, Black,
      and Non-Latino White emergency department (ED) patients. In addition, ED
      patients' use rates were compared with those of a statewide sample. METHODS:
      Trained bilingual/bicultural health educators screened almost 53,000 ED patients
      in 8 ED/trauma units throughout San Diego County over a 2-year period. Measures
      included sociodemographic characteristics and tobacco use measures from the
      Alcohol, Smoking, and Substance Involvement Screening Test brief screening
      instrument. RESULTS: A consistent finding was the lower prevalence of tobacco use
      among Latino patients compared with Black and Non-Latino White patients. Compared
      with their general population counterparts, Non-Latino White, Latino, and Black
      patients were more likely to have used tobacco in their lifetime and on a daily
      basis. CONCLUSIONS: Results indicate the high tobacco risk status of ED patients,
      regardless of ethnicity. More work is needed to develop effective approaches for
      ED-initiated tobacco interventions for patients in various racial/ethnic groups.
      Offering tobacco cessation support in opportune venues such as the ED holds great
      potential to improve accessibility to public health interventions for many
      underserved communities who may not have regular interaction with a primary care
      provider.

PMID- 21742652
TI  - Intrathyroid parathyroid carcinoma with intrathyroidal metastasis to the
      contralateral lobe: source of diagnostic and treatment pitfalls.
AB  - Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with
      potentially multiple diagnostic pitfalls. We report a case of 40-year-old man
      presented with classical manifestations of primary hyperparathyroidism, severe
      hypercalcemia and profoundly increased serum parathyroid hormone level. Neck
      ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in
      left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe.
      Routine percutaneous fine-needle aspiration of predominant nodule indicated
      follicular thyroid carcinoma, while left inferior nodule was confirmed to be of
      parathyroid origin. The patient underwent surgery, during which frozen sections
      identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph
      node. Permanent sections of the predominant left lobe nodule revealed
      intrathyroidal parathyroid carcinoma surrounded with multiple microscopic
      metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm
      intrathyroidal metastasis of primary parathyroid carcinoma was found within right
      thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative
      biopsy are of limited value in diagnosing parathyroid carcinoma, especially if
      localized intrathyroidally. Oncological en-block resection is treatment of
      choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly
      described case of intrathyroidal parathyroid carcinoma causing intrathyroidal
      dissemination may influence future treatment strategies.

PMID- 21742653
TI  - Combination chemotherapy with carboplatin and paclitaxel for advanced thymic
      cancer.
AB  - OBJECTIVE: Thymic carcinoma is a rare cancer of the thymus, different from
      thymoma in respect of its malignant nature, and no standard chemotherapy for this
      cancer has been established yet. METHODS: We conducted a retrospective review of
      the efficacy of combination chemotherapy with carboplatin (an area under the
      curve of 6) and paclitaxel (200 mg/m(2)) in 16 patients with histologically or
      cytologically proven thymic carcinoma, Masaoka Stage IVa/IVb or post-operative
      recurrent disease. RESULTS: There were 13 males and 3 females, with a median
      (range) age of 56 (38-73) years. Squamous cell carcinoma was the most common (n=
      12), followed by undifferentiated carcinoma (n= 2) and others (n= 2). Four, nine
      and three patients had Stage IVa, IVb and post-operative recurrent disease,
      respectively. Two and four patients showed complete and partial responses,
      respectively, representing a response rate (95% confidence interval) of 37.5
      (15.2-64.6)%. The median (95% confidence interval) progression-free and overall
      survivals in the 16 patients were 8.6 (1.8-15.3) and 49.4 (30.1-68.8) months,
      respectively. CONCLUSIONS: Combination therapy with carboplatin and paclitaxel
      yielded an objective response in about one-third of the patients with advanced
      thymic carcinoma.

PMID- 21742654
TI  - Efficacy of concurrent chemoradiotherapy as a palliative treatment in stage IVB
      esophageal cancer patients with dysphagia.
AB  - OBJECTIVE: To retrospectively assess the efficacy and safety of palliative
      chemoradiotherapy in Stage IVB esophageal cancer patients with dysphagia due to
      the primary lesion. METHODS: Forty patients with dysphagia caused by metastatic
      esophageal cancer, which had been treated between January 2004 and June 2009,
      were retrospectively investigated. The treatment consisted of two courses of
      chemotherapy (5-fluorouracil and cisplatin) and concurrent irradiation of 40 Gy
      in 20 fractions to the esophageal primary tumor. The grade of dysphagia was
      evaluated; nutrition-support-free survival was evaluated using the status of
      nutritional support of patients. Response to treatment, overall survival,
      progression-free survival and toxicities were also evaluated. RESULTS: Dysphagia
      score improved in 75% of the patients. Seventeen of the 20 patients (85%) who had
      required nutritional support at baseline improved their oral intake to no longer
      need the support, in a median time of 43 days. The median nutrition-support-free
      survival was 301 days in the 20 patients who had had adequate oral intake before
      the treatment. Disease control rate of the primary lesion was 95%, including 12
      patients (30%) who achieved a complete response. The overall response rate was
      55%. The median survival was 308 days, and the 1-year-survival rate was 45.0%.
      The median progression-free survival was 139 days. Toxicities were generally well
      tolerated. Major toxicities (Grade 3 or 4) involved hemoglobin (23%), leukocytes
      (15%), neutrophils (20%), anorexia (10%), nausea (3%), esophageal perforation
      (5%) and febrile neutropenia (3%). Two patients (5%) died within 30 days of
      terminating radiotherapy. CONCLUSIONS: Palliative chemoradiotherapy using 5
      fluorouracil plus cisplatin combined with concurrent 40 Gy irradiation
      effectively improved the symptom of dysphagia in Stage IVB esophageal cancer with
      acceptable toxicity and favorable survival.

PMID- 21742655
TI  - Autostereoscopic three-dimensional viewer evaluation through comparison with
      conventional interfaces in laparoscopic surgery.
AB  - In the near future, it is likely that 3-dimensional (3D) surgical endoscopes will
      replace current 2D imaging systems given the rapid spreading of stereoscopy in
      the consumer market. In this evaluation study, an emerging technology, the
      autostereoscopic monitor, is compared with the visualization systems mainly used
      in laparoscopic surgery: a binocular visor, technically equivalent from the
      viewer's point of view to the da Vinci 3D console, and a standard 2D monitor. A
      total of 16 physicians with no experience in 3D interfaces performed 5 different
      tasks, and the execution time and accuracy of the tasks were evaluated. Moreover,
      subjective preferences were recorded to qualitatively evaluate the different
      technologies at the end of each trial. This study demonstrated that the
      autostereoscopic display is equally effective as the binocular visor for both low
      and high-complexity tasks and that it guarantees better performance in terms of
      execution time than the standard 2D monitor. Moreover, an unconventional task,
      included to provide the same conditions to the surgeons regardless of their
      experience, was performed 22% faster when using the autostereoscopic monitor than
      the binocular visor. However, the final questionnaires demonstrated that 60% of
      participants preferred the user-friendliness of the binocular visor. These
      results are greatly heartening because autostereoscopic technology is still in
      its early stages and offers potential improvement. As a consequence, the authors
      expect that the increasing interest in autostereoscopy could improve its
      friendliness in the future and allow the technology to be widely accepted in
      surgery.

PMID- 21742656
TI  - Enhancing sternal closure using Kryptonite bone adhesive: technical report.
AB  - A novel approach to enhance the mechanical stability of primary sternal closure
      is described. An osteoconductive bone adhesive is used to augment conventional
      wire cerclage. More than 30 patients have undergone primary sternal closure using
      Kryptonite bone adhesive. All patients recovered well with no adverse side
      effects or adhesive-associated complications. Adhesive-enhanced sternal closure
      may accelerate functional recovery after sternotomy, improve early outcomes and
      prevent major sternal complications such as deep sternal wound infection and
      dehiscence. The technique is simple, safe, and expedient.

PMID- 21742657
TI  - An alternative system for transvaginal removal of dermoid cyst and a comparative
      study with laparoscopy.
AB  - The objective was to introduce a new system for transvaginal removal of ovarian
      cyst and to evaluate its feasibility. With a new transvaginal system, ultrasound
      assisted culdotomy, and laparoscopy supported cystectomy if vaginal procedure
      failed. The authors conducted a retrospective review in which 35 cases using new
      vaginal ovarian cystectomy were compared with 40 cases of laparoscopic cystectomy
      for the treatment of dermoid cyst. All cystectomies were completed without
      conversion to laparotomy and complications. In a case from vaginal group,
      laparoscopy was required. No differences existed in operating time, hemoglobin
      decrease, and C-reactive protein value between groups. Laparoscopically supported
      vaginal ovarian cystectomy with ultrasound-guided culdotomy was equivalent to
      laparoscopic cystectomy as to invasiveness and preserved the option of a
      completely vaginal approach. When a presumed benign dermoid cyst is located in
      cul-de-sac, this operation may represent a preferable alternative to an
      exclusively laparoscopic or exclusively vaginal ovarian cystectomy.

PMID- 21742658
TI  - Hiding intersphincteric and transphincteric sepsis in a novel pathological
      approach to chronic anal fissure.
AB  - AIM: The purpose of this study was to investigate whether endoanal
      ultrasonographic findings could better characterize chronic anal fissures, mostly
      in those patients with persistent and recurrent disease after medical treatment.
      METHODS: Between January 2004 and April 2010, patients referred to our
      departments suspected for anal fissure were considered in a database. Physical
      examination and anoscopy confirmed the diagnosis of anal fissure in 543 patients.
      Chronicity was defined on the basis of morphological features of the fissure and
      mainly on its persistence or recurrence after medical therapy. Moreover, 172 out
      of 543 patients were selected with respect to the inclusion criteria and
      submitted to endoanal ultrasonography. RESULTS: Seventeen out of 172 were
      anterior fissures (9.8%) and 155 posterior (90.2%). In 112 (65.1%) out of 172
      patients submitted to endoanal ultrasonography, an associated chronic abscess was
      demonstrated, with expression of 91 intersphincteric and 21 low transphincteric
      fistulas, respectively. According to clinical data as well as comorbidities and
      previous surgery, there were no significant differences between patients with
      associated abscess and those with only chronic anal fissure. CONCLUSION: The
      authors assume that chronic fissures may persist because of hiding sepsis in the
      anal canal and that chronic anal fissure might be the clinical and pathological
      expression of a coexisting intersphincteric or low transphincteric fistula, and
      the ultrasonographic findings strongly support this theory.

PMID- 21742659
TI  - Antibacterial mesh: a novel technique involving naturally occurring cellular
      proteins.
AB  - BACKGROUND: Naturally occurring antimicrobial peptides are possibly the "next
      frontier" in infection prevention. Binding them to mesh could reduce the rate of
      mesh infections. This study identifies an antimicrobial agent capable of
      significant antibacterial activity when bound to mesh. METHODS: Lysozyme, human
      beta defensin (HBD-3), human cathelicidin (LL-37), and lysostaphin were adsorbed
      to polypropylene mesh at various concentrations. Treated meshes were placed in a
      suspension of 1 * 10(6) Staphylococcus aureus. Antibacterial action was monitored
      by turbidimetric assay, fluorescent imaging, and a colony counting method.
      RESULTS: A very high rate of lysis of S aureus cells was observed in the
      lysostaphin-treated group as measured by optical density; none survived as seen
      on colony count assays. Optical density for mesh coated with lysozyme, HBD-3, and
      LL-37 did not differ from untreated controls, with 100% survival rates by colony
      counts. CONCLUSION: Lysostaphin had superior antibacterial activity following
      adsorption to mesh.

PMID- 21742660
TI  - Laparoscopic Nissen-Rossetti fundoplication is a safe and effective treatment for
      both Acid and bile gastroesophageal reflux in patients poorly responsive to
      proton pump inhibitor.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of laparoscopic
      Nissen-Rossetti fundoplication in patients with gastroesophageal reflux disease
      (GERD) poorly responsive to standard dose proton pump inhibitor (PPI) therapy.
      METHODS: A total of 35 patients (19 women, 16 men, mean age 44.6 +/- 14.01 years)
      were enrolled. All the patients underwent symptom questionnaires, upper
      gastrointestinal endoscopy, esophageal manometry, and combined 24-hour esophageal
      pH and bilirubin monitoring. Following this, the patients with persistent
      pathological esophageal acid and/or bilirubin exposure underwent laparoscopic
      antireflux surgery, followed by clinical and instrumental 12-month follow-up.
      RESULTS: One year after surgery, there was a significant improvement of symptom
      score, compared with standard PPI dose period (3.54 +/- 1.67 vs 20.8 +/- 10.9, P
      < .0001; paired t test) and mean percentage total time acid and bile exposure
      showed a significant decrease (4.9 +/- 2.9 vs 2.03 +/- 0.74 and 8.3 +/- 3.03 vs
      0.84 +/- 0.56, P < .0001; paired t test). CONCLUSIONS: In patients with GERD
      poorly responsive to standard PPI dose, laparoscopic Nissen-Rossetti
      fundoplication appears to be a safe and effective treatment of symptoms,
      esophageal damage, as well as both acid and bile reflux.

PMID- 21742661
TI  - New backstrap vagus electrode for continuous intraoperative neuromonitoring in
      thyroid surgery.
AB  - INTRODUCTION: Continuous intraoperative neuromonitoring (CIONM) via vagal nerve
      stimulation allows real-time surveillance of the recurrent laryngeal nerve during
      thyroid surgery. However, for effective CIONM, subtle changes in recurrent
      laryngeal nerve conductivity have to be detected. A newly developed stimulation
      electrode that provides stable nerve stimulation and safe application is
      presented. METHODS: For electrode validation, current distribution was simulated
      with the finite element method. Mechanical characteristics were assessed through
      bench testing. Clinical evaluation was initiated with 11 thyroid surgeries.
      RESULTS: Experimental and clinical results led to the development of a tripolar
      gold/polyimide electrode mounted onto a backstrap-shaped silicone body. It
      facilitated rapid electrode implantation and extraction (median implantation time
      4 +/- 19 seconds). Peak extraction force was 570 mN. Median supramaximal
      stimulation currents were 2.00 +/- 0.95 mA and resulted in reliable
      electromyogram responses (median 3.1 +/- 3.0 mV). No intraoperative electrode
      dislocations occurred, and no postoperative nerve palsy was observed. CONCLUSION:
      The new backstrap vagal stimulation electrode meets the requirements for reliable
      CIONM.

PMID- 21742662
TI  - Inguinal hernia orifice for specimen extraction after laparoscopic resections.
AB  - Specimen extraction is an unavoidable step in all laparoscopic resections. To
      this day there is no standardized retrieval incision for each procedure and the
      choice is made individually, yet based on the surgeon's experience and
      preference. Additionally, worldwide prevalence of inguinal hernia is high and
      many patients with this condition require surgical intervention for a distinct
      reason. In these particular cases, the hernia orifice can be seeing as an
      opportunity, allowing specimen retrieval when an open repair is performed
      immediately after the laparoscopic resection. In the present article, the authors
      propose this new option. Three patients who underwent this technique are also
      presented. Discussion is focused on the advantages and critics of the approach.

PMID- 21742663
TI  - Perirectal NOTES access: "down-to-up" total mesorectal excision for rectal
      cancer.
AB  - OBJECTIVES: Clinical natural orifice surgery has been applied for abdominal
      surgery in recent years, mostly by vaginal and oral access. The study describes
      preliminary successful human applications of transcolonic natural orifice
      transluminal endoscopic surgery (NOTES), using a new transrectal total mesorectal
      excision procedure for rectal cancer. METHODS: Institutional review board
      approval was obtained for the study. In 2 patients with rectal adenocarcinoma,
      total mesorectal resection and rectosigmoidectomy with lymphadenectomy was
      performed using a low NOTES transcolonic access. "Down-to-up" mesorectal
      dissection was achieved either using a flexible scope or a transrectal single
      port device. The specimens were extracted transanally, and transorificial low
      anastomosis was performed. RESULTS: Operative time was 350 and 360 minutes,
      respectively; no complications occurred and patients were discharged after 6
      days. CONCLUSION: Successful human reports on transcolonic NOTES suggest
      potential applications. The treatment of colorectal diseases through
      transorificial single port or flexible perirectal NOTES access are promising new
      approaches besides current methods to improve patient care.

PMID- 21742664
TI  - Totally endoscopic magnetic enteral bypass by external guided rendez-vous
      technique.
AB  - OBJECTIVE: This study aimed to assess the feasibility of a totally endoscopic
      enteral bypass using a self-orienting, dual ring, magnetic anastomosis system
      (MAGNAMOSIS) guided by a magnetic tracking system (3D METRIS). MATERIALS AND
      METHODS: In an anesthetized pig, 2 endoscopes were advanced, one each into the
      stomach and the colon. Both endoscopes were equipped with a MAGNAMOSIS ring
      secured with an endoscopic snare and a 3D METRIS within one working channel. The
      whole procedure was followed laparoscopically. The tracking system guided tips of
      endoscopes to a "rendez-vous" location between the colon and stomach. RESULTS:
      MAGNAMOSIS magnets automatically joined in the correct configuration when guided
      to within 2 cm of each other. At necropsy, magnetic rings were secure without
      entrapment of excess bowel or mesentery. CONCLUSION: An endoscopic enteral bypass
      with magnetic anastomosis and magnetic tracking device was feasible. More
      accurate tracking and advanced techniques could enable endoscopic bypasses at
      multiple sites in the gastrointestinal tract.

PMID- 21742665
TI  - Adoption of surgical innovations: factors influencing use of sentinel lymph node
      biopsy for breast cancer.
AB  - PURPOSE: Sentinel lymph node biopsy (SLNB) has been unevenly adopted into
      practice in Canada. In this qualitative study, the authors explored individual,
      institutional, and policy factors that may have influenced SLNB adoption. This
      information will guide interventions to improve SLNB implementation. METHODS:
      Qualitative methodology was used to examine factors influencing SLNB adoption.
      Grounded theory guided data collection and analysis. Semistructured interviews
      were based on Roger's diffusion of innovation theory. Purposive and snowball
      sampling was used to identify participants. Semistructured telephone interviews
      were conducted with urban, rural, academic, and community health care providers
      and administrators to ensure all perspectives and motivations were explored. Two
      individuals independently analyzed data and achieved consensus on emerging themes
      and their relationship. RESULTS: A total of 43 interviews were completed with 21
      surgeons, 5 pathologists, 7 nuclear medicine physicians, and 10 administrators.
      Generated themes included awareness of SLNB with the exception of some
      administrators, acknowledged advantage of SLNB, SLNB compatibility with beliefs
      regarding axillary staging, acknowledgment that SLNB was a complex innovation to
      adopt, extensive trialing of SLNB prior to adoption, observable benefits with
      SLNB, acknowledgment that hospital-level administrative support enabled adoption,
      desire for a provincial policy supporting SLNB to assist in hospital-level
      adoption, requirement of a local high-volume breast surgery champion who
      communicated extensively with team to facilitate local adoption, and need for
      credentialing of SLNB to ensure quality. CONCLUSIONS: SLNB is a complex
      innovation to adopt. Successful adoption was assisted by a high-volume breast
      cancer surgical champion, interprofessional communication, and administrative
      support.

PMID- 21742666
TI  - Comparison of the compression anastomosis ring (EndoCAR) with a circular stapled
      anastomosis in a porcine model.
AB  - PURPOSE: The aim of this study was to compare characteristics of rectal
      compression and stapled anastomoses at multiple time points. METHODS: A total of
      50 domestic pigs underwent a rectal anastomosis with a compression device or a
      circular stapler. They were sacrificed at zero-time, 2 days, 1 week, 1 month, and
      3 months. Burst and maximal tolerated pressure and sites of failure, internal
      diameters, and radiographic leak rates were assessed. Desmosine (elastin) levels
      were determined. RESULTS: There were no clinical or radiographic leaks. Overall,
      10 out of 27 (37%) compression anastomoses burst at higher pressures than the 14
      out of 24 (58%) stapled anastomoses. Mean circumference and anastomotic index
      were greater for the EndoCAR at 1 week and 3 months. Desmosine levels were
      similar. CONCLUSIONS: In the porcine model, compression rectal anastomoses with
      the EndoCAR had improved bursting pressures and internal circumference compared
      with circular stapled anastomoses.

PMID- 21742667
TI  - Amoxicillin-clavulanate improves symptoms, reduces treatment failure in select
      children with acute otitis media and increases risk of diarrhoea.

PMID- 21742668
TI  - Cardiac resynchronisation therapy reduces mortality in patients with heart
      failure but questions remain.

PMID- 21742669
TI  - The intuitive appeal of case series thinking: a challenge for evidence-based
      teaching and practice.

PMID- 21742670
TI  - Characteristics of women who do and do not receive onsite shelter services from
      domestic violence programs.
AB  - Shelter services are an essential means of providing help to women who are
      victims of intimate partner violence (IPV), but not all victims receive shelter.
      This article reports the results of a secondary analysis of statewide data from
      women using IPV services, comparing victims who did and did not obtain shelter.
      The demographic characteristics, abuse experiences, and service patterns of these
      survivors are examined. A model predicting characteristics associated with the
      likelihood of shelter receipt indicates that women who obtain shelter are more
      vulnerable and obtain more services than women who do not obtain shelter. The
      implications of these results are discussed.

PMID- 21742671
TI  - Combined bioluminescence and fluorescence imaging visualizing orthotopic lung
      adenocarcinoma xenograft in vivo.
AB  - Lung adenocarcinoma is the most common type of lung cancer. A close monitor of in
      vivo tumor development may help to better understand the pathogenesis and
      pathological processes of this disease. A bimodal imaging strategy has been
      developed, which is a very important tool to investigate the growth and
      metastasis of lung adenocarcinoma. In the present study, we used a combined
      labeling strategy in p53RE-luc-A549 cells via transfecting the reporter gene
      EGFP. In order to unambiguously identify the growth and metastasis of transfected
      A549 tumor cells, we established and observed subcutaneous and orthotopic
      xenografts in nude mice by in vivo bioluminescence and fluorescence imaging,
      which was verified by our post-mortem histological analysis. In vivo
      bioluminescence signal was observed for the progression of both subcutaneous and
      orthotopic xenografts in EGFP-p53RE-luc-A549 cells; in vivo fluorescence was only
      observed for the growth of subcutaneous xenograft of EGFP-p53RE-luc-A549 cells.
      Moreover, EGFP-p53RE-luc-A549 cells allow for the improved identification of
      implanted cells within host tissue during histological analysis. In conclusion,
      we presented a combined labeling strategy for bimodal A549 cell imaging which
      leads to improved detection of cellular grafts.

PMID- 21742672
TI  - 1-Aminocyclopropane-1-carboxylic acid synthase 2 is phosphorylated by calcium
      dependent protein kinase 1 during cotton fiber elongation.
AB  - The reaction catalyzed by 1-aminocyclopropane-1-carboxylic acid synthase (ACS) is
      proposed to be the rate-limiting step in ethylene biosynthesis, which has been
      found as one of the most up-regulated metabolic pathways during cotton fiber
      development. However, the transcripts of the identified ACS genes did not
      increase in a similar manner as those of 1-aminocyclopropane-1-carboxylic acid
      oxidase (ACO) genes, implicating a possible post-transcriptional modification or
      regulatory mechanism. In this work, cotton ACS2 was shown to interact with Ca(2+)
      dependent protein kinase 1 (CPK1). Bacterially expressed and purified recombinant
      ACS2 was phosphorylated by CPK1 in vitro and site-directed mutagenesis studies
      suggest that ACS2 S460 is a possible phosphorylation site for CPK1.
      Phosphorylated ACS2 significantly increased ACS activity, leading to elevated
      ethylene production. We thus speculated that CPK1 is involved in cotton fiber
      growth regulation by phosphorylating ACS2, which results in enhanced ethylene
      production in vitro.

PMID- 21742673
TI  - The effects of prenatal stress on expression of CaMK-II and L-Ca2+ channel in
      offspring hippocampus.
AB  - The purpose of the present study was to characterize the expressions of
      phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CaMK-II), total
      CaMK-II, and L-type Ca(2+) channel in offspring hippocampus that was induced by
      prenatal restraint stress. Pregnant rats were divided into two groups: the
      control group and the prenatal stress (PNS) group. Pregnant rats in the PNS group
      were exposed to restraint stress on day 14-20 of pregnancy three times daily for
      45 min. Adult offspring rats were used in this study. The results demonstrated
      that prenatal restraint stress induced a significant increase in the expression
      of p-CaMK-II, total CaMK-II, and L-Ca(2+) channel by western blot analysis in
      offspring hippocampus. The immunohistochemistry results revealed that PNS
      increased the expressions of CaMK-II and L-Ca(2+) channel in the hippocampal CA3
      of offspring rats. These data suggest that PNS can have long-term neuronal
      effects within hippocampal structure involved in the feedback mechanisms of the
      hypothalamo-pituitary-adrenal axis.

PMID- 21742674
TI  - Plasmid-mediated gene therapy for cardiovascular disease.
AB  - Gene transfer within the cardiovascular system was first demonstrated in 1989
      yet, despite extensive basic-science and clinical research, unequivocal benefit
      in the clinical setting remains to be demonstrated. Potential reasons for this
      include the fact that recombinant viral vectors, used in the majority of clinical
      studies, have inherent problems with immunogenicity that are difficult to
      circumvent. Attention has turned therefore to plasmid vectors, which possess many
      advantages over viruses in terms of safety and ease of use, and many clinical
      studies have now been performed using non-viral technology. This review will
      provide an overview of clinical trials for cardiovascular disease using plasmid
      vectors, recent developments in plasmid delivery and design, and potential
      directions for this modality of gene therapy.

PMID- 21742675
TI  - FoxO3 hastens autophagy and shrinks the heart but does not curtail pathological
      hypertrophy in adult mice.

PMID- 21742676
TI  - Virus-free iPS-derived cardiomyocytes: a new piece in the puzzle of patient
      tailored therapies.

PMID- 21742677
TI  - Ryanodine receptors: waking up from refractoriness.

PMID- 21742678
TI  - Role of early intravenous to oral antibiotic switch therapy in the management of
      prosthetic hip infection treated with one- or two-stage replacement.
AB  - OBJECTIVES: To determine outcomes for an antibiotic regimen using early switch to
      oral antibiotics for treatment of infected total hip replacement (THR) treated by
      either a one-stage or two-stage procedure. METHODS: Cases of infected THR were
      identified from the microbiology records on all orthopaedic infections in a 24
      month period. Diagnosis was made by microbiological culture of theatre specimens
      and findings at the time of surgery. A standard approach of 10-14 days
      intravenous (iv) antibiotic followed by a switch to oral antibiotics either for 6
      8 weeks until second-stage re-implantation or for up to 3 months following a one
      stage procedure was used. The exact date of oral switch and antibiotic duration
      was determined by clinical resolution and C-reactive protein (CRP). Outcome was
      recorded as no microbiological or clinical evidence of relapse of infection or
      relapse after completing the antibiotic course. Follow-up duration for all cases
      at the time of study was 24-36 months after completion of antibiotic treatment.
      RESULTS: In 24 months, 19 patients underwent two-stage THR for infection, of
      which 17 were treated with oral antibiotics after a median of 14 days initial iv
      antibiotics. None relapsed. Four patients underwent one-stage THR and had 12-20
      days iv then 6-26 weeks oral antibiotics with no relapse. CONCLUSIONS: Early oral
      antibiotic switch therapy was effective in patients treated at the Avon
      Orthopaedic Centre with infected THR and plays an important role in enabling
      patients to return to independence after revision surgery and avoid complications
      of prolonged iv access.

PMID- 21742679
TI  - False extended-spectrum {beta}-lactamase phenotype in clinical isolates of
      Escherichia coli associated with increased expression of OXA-1 or TEM-1
      penicillinases and loss of porins.
AB  - OBJECTIVES: Two clinical isolates of Escherichia coli, EC18 and EC21, were non
      susceptible (MICs 4-16 mg/L) to cefpirome and cefepime, with marked synergy with
      clavulanate, yet were susceptible to cefotaxime and ceftazidime (MICs <= 1 mg/L).
      EC19, from the same patient as EC21, was susceptible to all four cephalosporins.
      We sought to characterize the molecular basis of resistance in isolates EC18 and
      EC21. METHODS: PFGE was used to study the genetic relationships of the isolates,
      and MICs were determined. beta-Lactamases were characterized by PCR, isoelectric
      focusing (IEF), construction of genomic libraries and sequencing. A double mutant
      of E. coli J53 was constructed, lacking OmpC and OmpF porins. Plasmids from
      clinical isolates were transformed into E. coli J53 and J53DeltaompCF. Outer
      membrane proteins (OMPs) were analysed by SDS-PAGE and OmpA by matrix-assisted
      laser desorption ionization time-of-flight/time-of-flight mass spectrometry.
      Expression of omp and bla genes was analysed by RT-PCR. RESULTS: Isolates EC19
      and EC21 had identical PFGE profiles, whereas EC18 was distinct. PCR and IEF
      confirmed beta-lactamases with pIs of 5.4 (TEM-1) in EC18 and 7.4 (OXA-1) in both
      EC19 and EC21. EC18 had bla(TEM-1b) with the strong promoter P5 and lacked OmpC
      and OmpF. RT-PCR showed stronger expression of bla(OXA-1) in EC21 versus EC19,
      along with diminished expression of OmpC, though with increased OmpF. Plasmids
      extracted from EC18 and EC21 conferred increased MICs of cefpirome and cefepime,
      although susceptibility to cefotaxime and ceftazidime was retained. CONCLUSIONS:
      The 'cefpiromase' or 'cefepimase' ESBL phenotype of the clinical isolates non
      susceptible to cefpirome and cefepime resulted from high expression of TEM-1 or
      OXA-1 beta-lactamases combined with loss of porins.

PMID- 21742680
TI  - Associations of high-grade glioma with glioma risk alleles and histories of
      allergy and smoking.
AB  - Glioma risk has consistently been inversely associated with allergy history but
      not with smoking history despite putative biologic plausibility. Data from 855
      high-grade glioma cases and 1,160 controls from 4 geographic regions of the
      United States during 1997-2008 were analyzed for interactions between allergy and
      smoking histories and inherited variants in 5 established glioma risk regions:
      5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and
      20q13.3 (RTEL1). The inverse relation between allergy and glioma was stronger
      among those who did not (odds ratio(allergy-glioma) = 0.40, 95% confidence
      interval: 0.28, 0.58) versus those who did (odds ratio(allergy-glioma) = 0.76,
      95% confidence interval: 0.59, 0.97; P(interaction) = 0.02) carry the 9p21.3 risk
      allele. However, the inverse association with allergy was stronger among those
      who carried (odds ratio(allergy-glioma) = 0.44, 95% confidence interval: 0.29,
      0.68) versus those who did not carry (odds ratio(allergy-glioma) = 0.68, 95%
      confidence interval: 0.54, 0.86) the 20q13.3 glioma risk allele, but this
      interaction was not statistically significant (P = 0.14). No relation was
      observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence
      interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk
      of smoking history with any of the risk alleles. The authors' observations are
      consistent with a recent report that the inherited glioma risk variants in
      chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of
      allergy and glioma.

PMID- 21742681
TI  - Induction and aggravation of atrioventricular valve regurgitation in the course
      of chronic right ventricular apical pacing.
AB  - AIMS: Valvular regurgitation, especially on the right side of the heart, is a
      common finding even in patients without endocardial pacing leads. The severity of
      valvular regurgitation can change after permanent pacemaker (PPM) implantation.
      Ventricular pacing has been shown to cause ventricular dysfunction. The purpose
      of this study was to evaluate the mid-term effects of right ventricular (RV)
      apical pacing on atrioventricular (AV) valvular regurgitation in patients with a
      normal left ventricular function before PPM implantation. METHODS AND RESULTS:
      Patients who required dual-chamber pacemakers due to a high-degree AV block were
      enrolled in the study. Initial echocardiography was performed before PPM
      implantation and re-evaluation by echocardiography was performed every 24 months
      thereafter. A total of 125 patients (61 male; mean age: 66.57 +/- 6.45 years)
      were included in the study, and 115 pacemaker-dependent patients were followed up
      (mean +/- SD; 4.08 +/- 0.8 years). Echocardiography demonstrated mild tricuspid
      regurgitation (TR) and mitral regurgitation (MR) in 70 (60.1%) and 34 (29.6%)
      patients before PPM implantation, respectively. Moderate TR and MR were detected
      in 10 (8.7%) and 1 (0.9%) patients, respectively. Thirty-six (31.6%) patients
      showed moderate-to-severe TR at long-term follow-up, compared with the 10 (8.7%)
      patients, who had the same degree of TR before RV apical pacing (P < 0.001). Mild
      and moderate MR were detected in 54 (47%) and 8 (7%) patients after PPM
      implantation on the last echocardiography(P < 0.001). Baseline systolic pulmonary
      artery pressure (PAP) was 29.24 +/- 8.45 mmHg, which increased to 36 +/- 11 mmHg
      on the last echocardiography (P < 0.001). CONCLUSION: Considering the
      haemodynamic effects at mid-term follow-up, left ventricular dysfunction is rare
      in patients with RV apical pacing and normal baseline left ventricular function.
      Right ventricular apical pacing is associated with a significant increase in the
      prevalence and severity of TR and MR.

PMID- 21742682
TI  - Meticillin-resistant Staphylococcus aureus in a harbour seal (Phoca vitulina).

PMID- 21742683
TI  - Antimicrobial susceptibility of Pseudomonas aeruginosa isolates from dogs with
      otitis externa.
AB  - Pseudomonas aeruginosa is a common cause of otitis externa in dogs, and treatment
      of these infections is becoming problematic because of the increasing number of
      multiresistant strains. The aim of the present study was to compare the in vitro
      activities of cefepime, ceftazidime, enrofloxacin, ciprofloxacin, gentamicin and
      ticarcillin/clavulanic acid against 104 strains of P aeruginosa isolated from
      dogs with otitis externa. Antimicrobial susceptibility and minimum inhibitory
      concentrations, in ug/ml, were evaluated by the E test (bioMerieux). The most
      active compound was ceftazidime, with 100 per cent efficiency. The majority of
      tested strains were susceptible to ticarcillin/clavulanic acid (89.4 per cent),
      followed by ciprofloxacin (88.5 per cent) and cefepime (60.6 per cent). The
      highest resistance was observed to enrofloxacin (51.9 per cent) and gentamicin
      (43.3 per cent). Large numbers of strains were intermediately susceptible to
      antibiotics registered for use in veterinary medicine in Croatia--enrofloxacin
      (47.1 per cent) and gentamicin (41.3 per cent).

PMID- 21742684
TI  - Xanthine urolithiasis in a Cavalier King Charles spaniel.

PMID- 21742685
TI  - UK to harmonise its pet travel rules in line with the EU.

PMID- 21742688
TI  - BVA President expresses concern about delay to badger cull in Wales.

PMID- 21742689
TI  - Husbandry skills for Afghan villagers.

PMID- 21742690
TI  - Research partnerships aim to benefit British dairy farmers.

PMID- 21742692
TI  - Nottingham Trent to accredit new BSAVA certificates.

PMID- 21742693
TI  - RCVS celebrates 50 years of veterinary nursing.

PMID- 21742695
TI  - Detecting oestrus in dairy cows.

PMID- 21742696
TI  - Meticillin-resistant strains of Staphylococcus pseudintermedius in companion
      animals.

PMID- 21742697
TI  - Changes to pet travel rules.

PMID- 21742698
TI  - Distribution category for oral copper supplements for sheep.

PMID- 21742699
TI  - Spinal pain and presumptive diagnosis of meningitis in young dogs.

PMID- 21742700
TI  - Necrotic ulcerative spirochaetal stomatitis in outdoor pigs.

PMID- 21742701
TI  - Disseminated Rhodococcus equi infection in goats in the UK.

PMID- 21742702
TI  - Economic incentives to promote healthier food purchases: exploring acceptability
      and key factors for success.
AB  - Despite increasing interest, little is known about the beliefs and views of the
      public in relation to the use of economic incentives as a means to promote
      healthy eating. This study explores views of ethnically and socioeconomically
      diverse shoppers regarding acceptability of economic incentives to promote
      healthier food purchases, and factors likely to affect the success of such
      schemes. Six focus groups (n = 36 participants; 14 Maori, 12 Pacific, 10 non
      ethnic specific low income), were held in Auckland, New Zealand, in October 2009.
      A general inductive approach was used to identify common themes. The single most
      important reported food purchasing influence was cost. Focus group participants
      viewed the concept of economic incentives to promote healthy eating positively,
      as long as such schemes provided worthwhile incentives, and were simple and
      convenient to use. The preferred option for delivery was a pre-loaded electronic
      swipe card. Fruit and vegetables were the food group most participants said they
      would like to see incentivized. There was marked variability in the incentive
      amount thought sufficient to promote participation in such a scheme. Our findings
      suggest economic incentives hold promise as a means to promote healthier
      household food purchases, and their effectiveness should be evaluated using
      robust, randomized trials.

PMID- 21742703
TI  - Review of issue: caregiver depression and a plan to manage resistance to care.

PMID- 21742705
TI  - Margaret A. Newman's theory of health as expanding consciousness.

PMID- 21742706
TI  - Nursing theory-guided research.
AB  - Theory-guided research has a long tradition in nursing that spans at least 50
      years. Yet the use of nursing theory with qualitative research approaches
      continues to raise questions. Grounded theory is selected by nurses as a research
      methodology to address research questions that are aimed at understanding the
      nuances of nursing communication processes. Nurse theorist Margaret Newman is
      recognized in this issue for her theoretical contributions to practice and
      research, and a Newman scholar is introduced who explains her use of grounded
      theory research methodology guided by Newman's theory of health as expanding
      consciousness.

PMID- 21742707
TI  - Health as expanding consciousness: a nursing perspective for grounded theory
      research.
AB  - Margaret Newman's theory of health as expanding consciousness provides an
      excellent nursing perspective for nursing grounded theory research studies.
      Application of this nursing theory to grounded theory research provides a unitary
      transformative paradigm perspective to the sociological underpinnings of grounded
      theory methodology. The fit between this particular nursing theory and grounded
      theory methodology is apparent when purpose, timing, process, and health outcomes
      of the two are compared. In this column, the theory of health as expanding
      consciousness is described and the theory's research as praxis methodology is
      compared to grounded theory methodology. This is followed by a description of how
      the theory of health as expanding consciousness can be utilized as a perspective
      for nursing grounded theory research.

PMID- 21742708
TI  - Rigor: lost in the quest for evidence-based practice.
AB  - The purpose of this column is to bring to light a lack of rigor in the design of
      randomized controlled trials. In this effort, basic tenets of quantitative design
      are considered including delineation of populations along with probability and
      non-probability sampling techniques in addition to defining random selection and
      random assignment. The idea that randomized controlled trials, considered the
      piece de resistance of the evidence-based practice movement, lack rigor because
      of their use of randomly assigned groups without random selection of subjects is
      presented.

PMID- 21742709
TI  - Betrayal and academic relationships.
AB  - Betrayal, or the violation of human trust, is an important phenomenon happening
      in nurse-nurse and nurse-other human relationships in healthcare contexts.
      Specifically, betrayal and breaches of trust surface in academic relationships
      cocreating tension and uncertainty. This column begins a discussion of the
      phenomenon as viewed through the lens of the humanbecoming ethical tenets.

PMID- 21742710
TI  - Fostering ethical thoughtfulness.

PMID- 21742711
TI  - Human dignity: a cornerstone of doctoral education in nursing.
AB  - Human dignity is foundational to nursing ethics in both the practice and
      educational arena. It is implicitly and explicitly woven throughout all ethical
      dialogue. This column offers insight into the ubiquitous nature of human dignity
      as it surfaced during a doctoral level ethics course. These examples are shared
      in light of the humanbecoming human dignity ethical tenets: reverence, awe,
      betrayal, and shame. The prevalence of dignity in ethical discussion serves as a
      reminder for nurses to carve out time for meaningful discussions regarding its
      importance to the nursing profession as a whole.

PMID- 21742712
TI  - Clarifying advanced practice nursing.

PMID- 21742713
TI  - Specialty and advanced practice nursing: discerning the differences.
AB  - Advanced practice nursing and specialty practice are terms that are often used
      interchangeably in nursing discourse. This column explores the inextricable link,
      as well as the differences between these two types of practice. Drawing differing
      conclusions about their specific and cooperative value enables nurses to
      construct innovative and creative approaches to their continued development that
      illuminates a path for disciplinary expansion. Congruent programs of education
      prepare nurses to communicate the distinctiveness of their many and varied
      contributions to the public with greater clarity and emphatic certainty.

PMID- 21742714
TI  - Expanding consciousness in nursing education and practice. Interview by Pamela
      Clarke.
AB  - This column focuses on the importance of Newman's work for the future of nursing
      and healthcare. Dorothy Jones takes a strong position that nursing science should
      be a driving force in the healthcare arena in today's world. Implications for
      education are addressed.

PMID- 21742715
TI  - Patterns in the lives of African American women with diabetes.
AB  - The experience of African American women with diabetes has not been fully
      understood to guide meaningful practice. This community-based collaborative
      action research, based on Newman's nursing theory of health as expanding
      consciousness, sought to understand the experience of African American women
      living with diabetes, and to envision new patterns of health by engaging women in
      dialogue about the meaning of their experiences. Interviews with 7 women revealed
      the multi-faceted nature of living with diabetes; blood sugars rise and fall with
      stress, depression, and trauma, as well as spiritual strength, mentors, and
      sister friends balance energy demands. Findings were woven into a spoken word
      narrative to engage the wider community in dialogue to gain new insights into how
      to live and relate in healthier ways. These findings give rise to a different
      model of community health and guide nurses to focus holistically on what is
      meaningful in the lives of their patients.

PMID- 21742716
TI  - Patterns of inquiry: curriculum as life experience.
AB  - Readers are invited to be actors in a text-based theatre, drawn into the stories
      with their own experiences and discerning patterns that reveal a narrative unity.
      I show how curriculum-building is inclusive of a teacher's autobiography, as well
      as the theoretical/philosophical commitments significant for teaching-learning.
      This is accomplished through thinking narratively about an experience with my Dad
      in the healthcare system while simultaneously teaching theory-guided nursing in
      higher education. Health as expanding consciousness is revealed through a
      research-as-praxis process that is the content for inquiry.

PMID- 21742717
TI  - Understanding experiences of spousal caregivers with health as expanding
      consciousness.
AB  - The purpose of this study was to recognize a unitary pattern within the lives of
      spousal caregivers following their spouses' discharge from the hospital after
      coronary artery bypass graft surgery. The unitary pattern emerged through four
      themes: dyadic relationship life patterns influenced caregivers' roles and
      responsibilities, life patterns of caring for self and others were altered, life
      patterns of certainty and knowing were limiting, awareness of life pattern gave
      meaning, and new perception on life left to live. The study added empirical
      support to the theory of health as expanding consciousness and provided a new way
      to examine the spousal caregiving experience.

PMID- 21742718
TI  - Integrative review of research related to Margaret Newman's theory of health as
      expanding consciousness.
AB  - Since 1978 when Margaret Newman first introduced her theory of health as
      expanding consciousness, the theory has been widely expanded upon by Newman and
      nursing scholars around the world. This manuscript provides an integrative review
      of research related to the theory of health as expanding consciousness and
      analyzes strengths, limitations, and directions for the future. A consistent
      method of praxis within a unitary, participatory worldview was found. Health as
      expanding consciousness praxis provides a lens for guiding and interpreting
      meaning and has cross-cultural appeal and utility.

PMID- 21742719
TI  - Nursing practice with families without a country.
AB  - The authors of this paper consider the stories of three North Korean refugee
      families in South Korea in light of the humanbecoming family model. These stories
      testify to the hardships and separations lived by such families, but also speaks
      to their courage and determination. The vulnerability of refugee-and asylum
      seeking persons to further exploitation and victimization is highlighted, as is
      the value for nurses who provide them with an understanding welcome and support.

PMID- 21742720
TI  - Health as expanding consciousness: implications for health policy as praxis.
AB  - The authors of this column explore the implications of Newman's theory of health
      as expanding consciousness for health policy. One aim is to expand the theory's
      practice methodology and praxis methods to the development of health policy, an
      under-represented area in the health as expanding consciousness literature. The
      second aim is to suggest a framework for policy development, the health as
      expanding consciousness policy protocol, and explore the possible impact that
      theory-guided policy may have on community and nursing efforts to transform
      health and public policy.

PMID- 21742721
TI  - Caring and nursing theory-guided practice.

PMID- 21742722
TI  - "Spirituality and spiritual self-care: expanding self-care deficit nursing
      theory" (White, Peters, & Schim, 2011).

PMID- 21742723
TI  - Effects of an anti-platelet drug on the prevention of steroid-induced
      osteonecrosis in rabbits.
AB  - OBJECTIVE: To investigate the effects of an anti-platelet drug (clopidogrel) on
      the prevention of steroid-induced osteonecrosis (ON) in rabbits. METHODS: Adult
      male Japanese white rabbits were divided into two groups and treated as follows:
      one group received daily clopidogrel mixed in normal saline (AP; n = 35), the
      other received only normal saline (NS; n = 30). One week after the
      administration, all rabbits were injected once intramuscularly with 20 mg/kg of
      methylprednisolone acetate into the right gluteus medius muscle. Three weeks
      after, both the femora and humeri were examined histopathologically for the
      presence of ON. The platelet aggregation assay and hematological examinations
      were performed before and after the steroid injection. RESULTS: The incidence of
      ON in the AP group (48.5%) was significantly lower than that observed in the NS
      group (73.3%). The platelet aggregations in the AP group were significantly
      inhibited by the administration of clopidogrel. The levels of total cholesterol
      and triglycerides showed no significant differences between the AP and NS group.
      CONCLUSION: The present experimental study demonstrated that the administration
      of an anti-platelet drug prevented steroid-induced ON in rabbits and that
      platelet aggregation seems to be one of the possible factors involved in the
      pathogenesis of steroid-induced ON.

PMID- 21742724
TI  - Do health beliefs, health care system distrust, and racial pride influence HPV
      vaccine acceptability among African American college females?
AB  - The promise of human papillomavirus (HPV) vaccines rests with the ability to
      promote widespread uptake especially among populations at high risk of cervical
      cancer and other associated disease outcomes. The purpose of this study was to
      examine health beliefs and culturally specific influences of HPV vaccine
      acceptability among African American college females. Approximately 76 percent of
      participants reported HPV vaccine acceptability. Predictors of acceptability
      included: higher perceived benefit and lower racial pride. Findings can be used
      to inform development of campus-based HPV educational approaches to promote
      widespread HPV vaccine acceptability and safer sex practices among African
      American college females.

PMID- 21742725
TI  - Telephone lifestyle coaching: is it feasible as a behavioural change intervention
      for men?
AB  - This study assessed the feasibility of a telephone lifestyle coaching
      intervention for middle aged and older men in a service club setting and
      evaluated its impact on behavioural change in terms of BMI, physical activity,
      dietary habits, self-reported quality of life and stages of change. Forty
      participants from Rotary clubs in Western Australia participated in this pilot
      intervention. Findings showed significant improvements in lifestyle risk
      modification indicators. Participants were very satisfied with the interaction
      with their coaches and rated highly the telephone as a medium for coaching.
      Findings suggested that telephone coaching was a feasible means of delivering a
      lifestyle intervention in a 'real-world' setting for a hard to reach population
      group.

PMID- 21742726
TI  - Substitution therapy for alcoholism: time for a reappraisal?
AB  - A number of compounds already in use as medications for various indications
      substitute for ethanol at clinically relevant brain pathways, in particular, at
      gamma-aminobutyric acid (GABA) receptors. Nevertheless, although substitute
      medications have been recognized for heroin and tobacco dependence, patients with
      alcohol dependence are rarely offered an analogous approach. Benzodiazepines may
      have paradoxical effects, and abuse and dependence are known. Baclofen (GABA(B)
      agonist) has not been associated with dependence or misuse and has been effective
      in several trials in preventing relapse, although research is required to
      establish the optimal dosing regimen. GABA-ergic anticonvulsants, helpful in
      treating withdrawal, have yet to emerge as effective in relapse prevention.
      Clomethiazole and sodium oxybate, the latter having been shown to be effective in
      relapse prevention, have incurred a reputation for dependence and abuse. However,
      data have emerged showing that the risk of abuse of sodium oxybate is lower than
      many clinicians had foreseen. For a condition where existing therapies are only
      effective in a proportion of patients, and which has high morbidity and
      mortality, the time now seems right for reappraising the use of substitute
      prescribing for alcohol dependence.

PMID- 21742728
TI  - Roger Dawson Milkman (1930-2011) geneticist.

PMID- 21742729
TI  - Inna Golubovskaya: the life of a geneticist studying meiosis.
AB  - Maize, with its excellent forward genetics and male sterility screens, was used
      to identify >50 meiotic mutants representing at least 35 genes that affect key
      prophase processes such as pairing, synapsis, and homologous recombination. Most
      of these mutants were found by Inna Golubovskaya during the course of her
      remarkable career as a cytogeneticist. In addition to undertaking general
      cytological surveys to classify mutant phenotypes, Golubovskaya focused her
      efforts on characterizing several key regulatory mutants: ameiotic1 (am1),
      required to establish the meiotic cell cycle in maize; absence of first division
      (afd1), required for proper prophase chromosome morphology and for meiotic sister
      chromatid cohesion leading to a reductive chromosome segregation at the first
      meiotic division; and plural abnormalities of meiosis (pam1), required for the
      clustering of telomeres on the nuclear envelope needed for pairing and synapsis.
      Her dramatic childhood in Leningrad during its siege in World War II, her
      fortuitous education in genetics at Leningrad State University, her continued
      research at the forward-looking Institute of Cytology and Genetics of the USSR
      Academy of Science Siberian branch, her plight at the fall of the Soviet Union,
      and her work in America helped engender a unique and valuable plant geneticist.
      Inna Golubovskaya related this personal history to the authors in conversation.

PMID- 21742730
TI  - Blocking TGF-beta1 protects the peritoneal membrane from dialysate-induced
      damage.
AB  - During peritoneal dialysis (PD), mesothelial cells undergo mesothelial-to
      mesenchymal transition (MMT), a process associated with peritoneal-membrane
      dysfunction. Because TGF-beta1 can induce MMT, we evaluated the efficacy of TGF
      beta1-blocking peptides in modulating MMT and ameliorating peritoneal damage in a
      mouse model of PD. Exposure of the peritoneum to PD fluid induced fibrosis,
      angiogenesis, functional impairment, and the accumulation of fibroblasts. In
      addition to expressing fibroblast-specific protein-1 (FSP-1), some fibroblasts co
      expressed cytokeratin, indicating their mesothelial origin. These intermediate
      phenotype (Cyto(+)/FSP-1(+)) fibroblasts had features of myofibroblasts with
      fibrogenic capacity. PD fluid treatment triggered the appearance of CD31(+)/FSP
      1(+) and CD45(+)/FSP-1(+) cells, suggesting that fibroblasts also originate from
      endothelial cells and from cells recruited from bone marrow. Administration of
      blocking peptides significantly ameliorated fibrosis and angiogenesis, improved
      peritoneal function, and reduced the number of FSP-1(+) cells, especially in the
      Cyto(+)/FSP-1(+) subpopulation. Conversely, overexpression of TGF-beta1 in the
      peritoneum by adenovirus-mediated gene transfer led to a marked accumulation of
      fibroblasts, most of which derived from the mesothelium. Taken together, these
      results demonstrate that TGF-beta1 drives the peritoneal deterioration induced by
      dialysis fluid and highlights a role of TGF-beta1-mediated MMT in the
      pathophysiology of peritoneal-membrane dysfunction.

PMID- 21742731
TI  - IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine
      production.
AB  - The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved
      in the pathogenesis of systemic lupus and lupus nephritis, but the contribution
      of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To
      determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient
      mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with
      increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice,
      resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting
      that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4
      deficiency completely protected these mice from glomerulonephritis and lung
      disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti
      dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of
      plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither
      developed immune complex disease nor glomerular activation of complement. In
      addition, lack of IRF4 impaired the maturation of Th17 effector T cells and
      reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute
      to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic
      inflammation and the activation of antigen-presenting cells but also prevents the
      maturation of plasma cells and effector T cells. Because these adaptive immune
      effectors are essential for the evolution of lupus nephritis, we conclude that
      IRF4 promotes the development of lupus nephritis despite suppressing antigen
      presenting cells.

PMID- 21742732
TI  - Information provision and decision-making in assisted reproduction treatment:
      results from a survey in Germany.
AB  - BACKGROUND: The objective of this study was to investigate the views of patients
      and experts in Germany on information provision and decision-making in assisted
      reproduction treatment (ART). METHODS: Standard questionnaire techniques were
      used for interviewing Reproductive Physicians (n= 230), Psychosocial Counsellors
      (n = 66) and Patients (n = 1590). Descriptive data analyses and non-parametric
      tests for significance were performed. RESULTS: Higher scores were assigned for
      information on the chances for treatment success and on direct, physical risks of
      fertility treatment than for information on the risks and burden of multiple
      pregnancies and on the emotional risks and burden associated with infertility
      treatment. Three-quarters (74%) of the Patients (P) reported that they had
      experienced an overwhelming desire for a child at some point during their
      treatment, and half (47%) stated that they had experienced the feeling of losing
      control over the situation. According to 25% of the Reproductive Physicians (RP)
      and 47% of the Psychosocial Counsellors (PC), patients are often or very often
      limited in their capacity to decide when to stop the treatment. CONCLUSIONS: A
      significant number of patients in reproductive care in Germany are not well
      informed on all the aspects that are relevant for treatment decision-making, are
      overwhelmed by their desire for a child, lose control over the situation, and are
      limited in their capacity to end unsuccessful treatment. Information provision
      should be ensured and monitored during treatment by standardized safeguards. A
      strategy for stopping ART and embarking on alternative ways of coping with
      infertility should be installed from the outset of every treatment.

PMID- 21742733
TI  - Patient satisfaction in two Chinese provinces: rural and urban differences.
AB  - OBJECTIVE: While international research on patient satisfaction on healthcare has
      grown tremendously in the past three decades, little research has been conducted
      concerning healthcare-related patient satisfaction in China. This study was
      designed to examine what factors including patients' characteristics and ease of
      access to care are associated with level of patient satisfaction and how such
      satisfaction might differ across rural and urban populations in China. This study
      also serves as an evaluation of the recent healthcare reforms that have taken
      place in China, which were expected to equalize satisfaction between rural and
      urban patients. DESIGN: A cross-sectional survey to assess satisfaction among
      patients attending county-level hospitals in China. SETTING: Forty county-level
      hospitals in two provinces of China. PARTICIPANTS: Twenty-five patients from each
      of the 40 county-level hospitals. MAIN OUTCOME MEASURE: Patient satisfaction
      measured with 15 questions. RESULTS: Perceived convenience was significantly
      associated with patient satisfaction among all participants. The new rural
      cooperative medical insurance scheme (NRCMIS) was associated with higher overall
      satisfaction among the rural residents. Age and income were significantly related
      to satisfaction only among rural patients. CONCLUSIONS: Rural residents benefit
      greatly from the implementation of NRCMIS. Future reform could be more effective
      by catering the needs of each specific group (e.g. low-income population, rural
      population, etc.) identified by this study.

PMID- 21742734
TI  - Abnormal bidirectional plasticity-like effects in Parkinson's disease.
AB  - Levodopa-induced dyskinesia is a major complication of long-term dopamine
      replacement therapy for Parkinson's disease that becomes increasingly problematic
      in advanced Parkinson's disease. Although the cause of levodopa-induced
      dyskinesias is still unclear, recent work in animal models of the corticostriatal
      system has suggested that levodopa-induced dyskinesias might result from abnormal
      control of synaptic plasticity. In the present study, we aimed to explore control
      of plasticity in patients with Parkinson's disease with and without levodopa
      induced dyskinesias by taking advantage of a newly developed protocol that tests
      depotentiation of pre-existing long-term potentiation-like synaptic facilitation.
      Long-term potentiation-like plasticity and its reversibility were studied in the
      motor cortex of 10 healthy subjects, 10 patients with Parkinson's disease and
      levodopa-induced dyskinesias, who took half of the regular dose of levodopa and
      10 patients with Parkinson's disease without levodopa-induced dyskinesias, who
      took either half or the full dose of levodopa. Patients with Parkinson's disease
      without levodopa-induced dyskinesias had normal long-term potentiation- and
      depotentiation-like effects when they took their full dose of levodopa, but there
      was no long-term potentiation-like effect when they were on half dose of
      levodopa. In contrast, patients with levodopa-induced dyskinesias could be
      successfully potentiated when they were on half their usual dose of levodopa;
      however, they were unresponsive to the depotentiation protocol. The results
      suggest that depotentiation is abnormal in the motor cortex of patients with
      Parkinson's disease with levodopa-induced dyskinesias and that their long-term
      potentiation-like plasticity is more readily affected by administration of
      levodopa than their clinical symptoms.

PMID- 21742735
TI  - Endogenous morphine-like compound immunoreactivity increases in parkinsonism.
AB  - Morphine is endogenously synthesized in the central nervous system and endogenous
      dopamine is thought to be necessary for endogenous morphine formation. As
      Parkinson's disease results from the loss of dopamine and is associated with
      central pain, we considered how endogenous morphine is regulated in the untreated
      and l-DOPA-treated parkinsonian brain. However, as the cellular origin and
      overall distribution of endogenous morphine remains obscure in the pathological
      adult brain, we first characterized the distribution of endogenous morphine-like
      compound immunoreactive cells in the rat striatum. We then studied changes in the
      endogenous morphine-like compound immunoreactivity of medium spiny neurons in
      normal, Parkinson's disease-like and l-DOPA-treated Parkinson's disease-like
      conditions in experimental (rat and monkey) and human Parkinson's disease. Our
      results reveal an unexpected dramatic upregulation of neuronal endogenous
      morphine-like compound immunoreactivity and levels in experimental and human
      Parkinson's disease, only partially normalized by l-DOPA treatment. Our data
      suggest that endogenous morphine formation is more complex than originally
      proposed and that the parkinsonian brain experiences a dramatic upregulation of
      endogenous morphine immunoreactivity. The functional consequences of such
      endogenous morphine upregulation are as yet unknown, but based upon the current
      knowledge of morphine signalling, we hypothesize that it is involved in fatigue,
      depression and pain symptoms experienced by patients with Parkinson's disease.

PMID- 21742738
TI  - How to improve surgical research.

PMID- 21742739
TI  - Libyan health system is "absolutely stretched," says UN.

PMID- 21742740
TI  - Secular trends in body mass index and the prevalence of overweight and obesity
      among children and adolescents in Shandong, China, from 1985 to 2010.
AB  - BACKGROUND: There is strong evidence of a positive secular trend in body mass
      index (BMI) and the prevalence of obesity has increased substantially over the
      last several decades. However, no studies on this trend have been reported in
      Shandong Province, China. The present study assessed the decennial change in BMI
      in Shandong Province during the past 25 years and the prevalence of overweight
      and obesity among children and adolescents. METHODS: The BMI of children and
      adolescents aged 7-18 was calculated using data from five national surveys on
      students' constitution and health carried out by the government in 1985, 1995,
      2000, 2005 and 2010 in Shandong Province, China. The distribution of BMI was
      reported, and the prevalence of overweight and obesity was obtained according to
      the screening criteria of overweight and obesity for Chinese students using BMI
      [Working Group on Obesity in China (WGOC) standard]. Overweight and obesity
      prevalence were also computed using the International Obesity Task Force (IOTF)
      cutoffs. RESULTS: In the past 25 years, the P(50) (50th percentile) of BMI
      increased. The average increments of BMI were 2.18 kg/m(2) for boys and 1.21
      kg/m(2) for girls, respectively. The prevalence of overweight and obesity
      increased rapidly: using WGOC standard, the prevalence of overweight increased
      from 1.91% for boys and 2.02% for girls in 1985 to 17.34% for boys and 11.97% for
      girls in 2010, and the prevalence of obesity increased from 0.27% for boys and
      0.23% for girls in 1985 to 15.83% for boys and 7.12% for girls in 2010; using
      IOTF standard, the prevalence of overweight increased from 1.54% for boys and
      1.27% for girls in 1985 to 19.06% for boys and 13.42% for girls in 2010, and the
      prevalence of obesity increased from 0.04% for boys and 0.03% for girls in 1985
      to 9.33% for boys and 2.42% for girls in 2010, respectively. CONCLUSIONS: The
      average value of BMI has increased over time; overweight and obesity among
      children and adolescents have become a serious public health problem.
      Comprehensive evidence-based strategies of intervention should be introduced,
      including periodic monitoring.

PMID- 21742741
TI  - Exposure-response relationship between chrysotile exposure and mortality from
      lung cancer and asbestosis.
AB  - OBJECTIVES: To describe mortality in workers exposed to chrysotile asbestos, and
      determine exposure-response relationships between asbestos exposure and mortality
      from lung cancer and asbestosis by fitting and comparing different models.
      METHODS: A prospective cohort consisting of 586 workers in an asbestos textile
      factory was followed from 1 January 1972 to 31 December 2006. A structured
      questionnaire was administered to collect personal information and exposure data.
      Paired concentration samples measured in the workshops were used to convert dust
      concentrations to fibre concentrations. Individual cumulative asbestos exposure
      was estimated as the product of fibre concentrations and duration of employment
      in each job and expressed as fibre-years/ml. The vital status of cohort members
      was followed annually. Poisson regression analysis was applied to fit log-linear,
      log-quadratic, power, additive relative risk and categorical models to estimate
      exposure-response relationships between cumulative fibre exposure and mortality
      from lung cancer and asbestosis. RESULTS: Of the 226 deaths (14.6 per 1000 person
      years) over the 35-year follow-up, 51 were from lung cancer (3.29 per 1000 person
      years) and 37 from asbestosis (2.39 per 1000 person-years). A significant
      exposure-response relationships with either lung cancer or asbestosis (p<0.001)
      was observed in the final model. The power model with lagged 10 years was found
      to be the best model of those evaluated for both lung cancer (beta
      coefficient=0.53) and asbestosis (beta coefficient=0.63). CONCLUSIONS: The study
      confirmed strong associations between exposure to chrysotile asbestos and lung
      cancer and asbestosis, in which clear exposure-response relationships were
      observed.

PMID- 21742742
TI  - Stillbirth and residential proximity to extremely low frequency power
      transmission lines: a retrospective cohort study.
AB  - OBJECTIVES: The relationship between electromagnetic field exposure and
      stillbirth has not been evaluated. We assessed associations between residential
      proximity to extremely low frequency power transmission lines and stillbirth
      across gestational age. METHODS: Data included singleton live births (N=514,826)
      and stillbirths (N=2033) for 1998-2007 in metropolitan areas of Quebec, Canada.
      Using power transmission line maps, the distances between lines and residential
      six-digit postal codes (<25, 25-49.9, 50-74.9, 75-99.9, >= 100 m) were
      calculated. Generalised estimating equations were used to compute ORs and 95% CIs
      for distance and stillbirth, accounting for individual and area characteristics.
      Early preterm (< 28 weeks), late preterm (28-36 weeks) and term (>= 37 weeks)
      stillbirths were examined relative to fetuses-at-risk. RESULTS: There was no
      association between distance and preterm stillbirth. The odds of term stillbirth
      for <25 m were greater compared to >= 100 m (OR 2.25, 95% CI 1.14 to 4.45), but
      no dose-response pattern was apparent. CONCLUSIONS: A graded dose-response trend
      between distance to lines and odds of stillbirth was not found, but the
      likelihood of term stillbirth was elevated for residences within 25 m of power
      transmission lines. Residential proximity to transmission lines is unlikely to be
      associated with stillbirth, but more research is needed to rule out a possible
      link.

PMID- 21742743
TI  - Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Genetic factors influencing lung function may predispose to chronic
      obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10)
      signalling pathway is critical for lung development and lung epithelial renewal.
      The hypothesis behind this study was that constitutive FGF10 insufficiency may
      lead to pulmonary disorder. Therefore investigation of the pulmonary functions of
      patients heterozygous for loss of function mutations in the FGF10 gene was
      performed. METHODS: The spirometric measures of lung function from patients and
      non-carrier siblings were compared and both groups were related to matched
      reference data for normal human lung function. RESULTS: The patients show a
      significant decrease in lung function parameters when compared to control values.
      The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted)
      and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1.
      Patients with FGF10 haploinsufficiency have lung function parameters indicating
      COPD. A modest response to Terbutalin confirms an irreversible obstructive lung
      disease. CONCLUSION: These findings support the idea that genetic variants
      affecting the FGF10 signalling pathway are important determinants of lung
      function that may ultimately contribute to COPD. Specifically, the results show
      that FGF10 haploinsufficiency affects lung function measures providing a model
      for a dosage sensitive effect of FGF10 in the development of COPD.

PMID- 21742744
TI  - The need for standardised outcome reporting in colorectal surgery.

PMID- 21742745
TI  - Ischaemic colitis associated with JAK2V617F mutation.

PMID- 21742746
TI  - Prehospital improvisation of standard oxygen therapy equipment to facilitate
      delivery of a bronchodilator in a supine patient.

PMID- 21742747
TI  - Callers' experiences of making emergency calls at the onset of acute stroke: a
      qualitative study.
AB  - BACKGROUND: Rapid access to emergency medical services (EMS) is essential at the
      onset of acute stroke, but significant delays in contacting EMS often occur.
      OBJECTIVE: To explore factors that influence the caller's decision to contact EMS
      at the onset of stroke, and the caller's experiences of the call. METHODS:
      Participants were identified through a purposive sample of admissions to two
      hospitals via ambulance with suspected stroke. Participants were interviewed
      using open-ended questions and content analysis was undertaken. RESULTS: 50
      participants were recruited (median age 62 years, 68% female). Only one of the
      callers (2%) was the patient. Two themes were identified that influenced the
      initial decision to contact EMS at the onset of stroke: perceived seriousness,
      and receipt of lay or professional advice. Two themes were identified in relation
      to the communication between the caller and the call handler: symptom description
      by the caller, and emotional response to onset of stroke symptoms. CONCLUSIONS:
      Many callers seek lay or professional advice prior to contacting EMS and some
      believe that the onset of acute stroke symptoms does not warrant an immediate 999
      call. More public education is needed to improve awareness of stroke and the need
      for an urgent response.

PMID- 21742748
TI  - Spontaneous anterior dislocation of a mature cataract following old trauma.
AB  - We report a case of a patient who incurred spontaneous anterior dislocation of a
      mature cataract which required prompt surgical removal. Some years previous to
      this, he had sustained blunt trauma to the eye.

PMID- 21742749
TI  - Retrospective case series analysis of penicillin allergy testing in a UK
      specialist regional allergy clinic.
AB  - INTRODUCTION: Penicillin allergy is the most common drug allergy. Skin testing
      for the major (PPL) and minor determinants (MDMs) of penicillin offers increased
      sensitivity and specificity over in vitro testing alone. Following a worldwide
      absence of reagents, a new kit was licensed in the UK in 2008 (Diater, Spain) and
      this report evaluates its use in a UK specialist allergy clinic. METHODS:
      Prospective data on 50 consecutive patients tested with the new reagents were
      collected. The departmental protocol is adapted from the 2003 EAACI position
      paper. RESULTS: 14% (7/50) and 12% (6/50) of patients were diagnosed with
      immediate and non-immediate reactions respectively. The negative predictive value
      of the PPL and MDM reagents at the neat concentration for an immediate reaction
      was 93% (true negatives 37, false negatives 3). Two patients experienced systemic
      reactions to DPT in the absence of demonstrable specific IgE. None of the
      patients were diagnosed using skin prick testing alone or at lower concentrations
      of IDT. Five patients were diagnosed at the IDT stage and two at the DPT stage in
      the absence of demonstrable specific IgE. Six patients were diagnosed with non
      immediate reactions, two on IDT alone and four following IDT and DPT. CONCLUSION:
      The new PPL and MDM determinants offer enhanced sensitivity when evaluating beta
      lactam hypersensitivity; however, there are limitations to the current testing
      regimens. The UK would benefit from local guidelines, which incorporate the new
      reagents and acknowledge the high amoxicillin prescription rate and the
      relatively lower specialist-to-patient ratio in this country.

PMID- 21742750
TI  - Expression of phosphoinositide-specific phospholipase C isoforms in human
      umbilical vein endothelial cells.
AB  - AIMS: The signalling system of phosphoinositides (PIs) is involved in a number of
      cell and tissue functions including membrane trafficking, ion channel activity,
      cell cycle, apoptosis, differentiation and cell and tissue polarity. Recently, a
      role in cell migration was hypothesised for PI and related molecules including
      the phosphoinositide-specific phospholipases C (PI-PLCs), main players in PI
      signalling. The expression of PI-PLCs is tissue-specific and evidence suggests
      that it varies under different conditions such as tumour progression or cell
      activation. In order to obtain a complete picture, the expression of all PI-PLC
      isoforms was analysed in human endothelial cells (EC). METHODS: Using molecular
      biology methods (RT-PCR), the expression of PI-PLC isoforms was analysed in human
      umbilical vein endothelial cells (HUVEC), a widely used experimental model for
      human EC. RESULTS: All the PI-PLC isoforms except PI-PLC beta1, PI-PLC epsilon
      and PI-PLC zeta were expressed in HUVEC. CONCLUSIONS: The growing interest in the
      complex cascade of events occurring in angiogenesis will provide useful insights
      for therapeutic strategies. The expression of PI-PLC isoforms in HUVEC is a
      useful tool for further studies directed to understanding their role in
      angiogenesis. However, although HUVEC represent a widely used experimental model
      for human macrovascular EC, limitations remain in that they cannot fully
      represent the metabolic properties and interactions of the EC distributed in the
      entire organism.

PMID- 21742751
TI  - Collagen triple helix repeat containing 1 protein, periostin and versican in
      primary and metastatic breast cancer: an immunohistochemical study.
AB  - BACKGROUND: Collagen triple helix repeat containing 1 (CTHRC1) affects Wnt
      signalling, collagen deposition and bone formation. It is an extracellular matrix
      protein which is also abnormally expressed in the tumour microenvironment. CTHRC1
      has not been studied in breast cancer by immunohistochemistry. AIMS: To examine
      expression of CTHRC1 together with periostin and versican in breast cancer
      patients and investigate its association with clinicopathological
      characteristics. METHODS: The formalin-fixed paraffin-embedded tissues of 173
      invasive carcinomas (classified into WHO histotypes and luminal, triple negative
      and Her2 subtypes), as well as normal tissues, precursor lesions and metastatic
      lymph nodes were stained by relevant antibodies, assessed semiquantitatively by
      histoscore and statistically evaluated. RESULTS: Expression of CTHRC1, versican
      and periostin was significantly higher in breast cancer than in normal tissue or
      precursor lesions. CTHRC1 stromal expression was enhanced in triple negative
      cases and also in patients with bone metastasis. Periostin expression was high in
      primary tumours, in particular triple negative ones, and also in their lymph node
      metastases. Cox regression analysis showed that in patients with high periostin,
      the risk of bone metastases increased with increased CTHRC1 expression.
      CONCLUSIONS: CTHRC1 and periostin play important roles in breast cancer
      progression. These preliminary results show that combined evaluation of CTHRC1
      and periostin could serve as a potential marker for breast cancer bone
      metastasis; the other observations contribute to the description of the tumour
      microenvironment, with implications for lymph node and bone metastasis.

PMID- 21742752
TI  - Re-excision perineural invasion in the skin.

PMID- 21742753
TI  - Slow wave propagation and plasticity of interstitial cells of Cajal in the small
      intestine of diabetic rats.
AB  - The number of myenteric interstitial cells of Cajal (ICC-MY), responsible for the
      generation and propagation of the slow wave in the small intestine, has been
      shown to decrease in diabetes, suggesting impairment of slow-wave (SW)
      propagation and related motility. To date, however, this expected decrease in SW
      propagation has neither been recorded nor analysed. Eleven rats were treated with
      streptozotocin and housed in pairs with 11 age-matched control animals. After 3
      or 7 months, segments of duodenum, jejunum and ileum were isolated and divided
      into two parts. One part was processed for immediate freezing, cryosectioning and
      immunoprobing using anti-c-Kit antibody to quantify ICC-MY. The second part was
      superfused in a tissue bath, and SW propagation was recorded with 121
      extracellular electrodes. In addition, a cellular automaton was developed to
      study the effects of increasing the number of inactive cells on overall
      propagation. The number of ICC-MY was significantly reduced after 3 months of
      diabetes, but rebounded to control levels after 7 months of diabetes. Slow-wave
      frequencies, velocities and extracellular amplitudes were unchanged at any stage
      of diabetes. The cellular automaton showed that SW velocity was not linearly
      related to the number of inactive cells. The depletion of ICC-MY is not as severe
      as is often assumed and in fact may rebound after some time. In addition, at
      least in the streptozotocin model, the initial reduction in ICC-MY is not enough
      to affect SW propagation. Diabetic intestinal dysfunction may therefore be more
      affected by impairments of other systems, such as the enteric system or the
      muscle cells.

PMID- 21742754
TI  - Contribution of excitatory amino acid receptors of the retrotrapezoid nucleus to
      the sympathetic chemoreflex in rats.
AB  - In the present study, we evaluated the role of glutamatergic mechanisms in the
      retrotrapezoid nucleus (RTN) in changes of splanchnic sympathetic nerve discharge
      (sSND) and phrenic nerve discharge (PND) elicited by central and peripheral
      chemoreceptor activation. Mean arterial pressure (MAP), sSND and PND were
      recorded in urethane-anaesthetized, vagotomized, sino-aortic denervated and
      artificially ventilated male Wistar rats. Hypercapnia (10% CO(2)) increased MAP
      by 32 +/- 4 mmHg, sSND by 104 +/- 4% and PND amplitude by 101 +/- 5%. Responses
      to hypercapnia were reduced after bilateral injection of the NMDA receptor
      antagonist d,l-2-amino-5-phosphonovalerate (AP-5; 100 mm in 50 nl) in the RTN
      (MAP increased by 16 +/- 3 mmHg, sSND by 82 +/- 3% and PND amplitude by 63 +/-
      7%). Bilateral injection of the non-NMDA receptor antagonist 6,7-dinitro
      quinoxaline-2,3-dione (DNQX; 100 mm in 50 nl) and the metabotropic receptor
      antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG; 100 mm in 50 nl) in
      the RTN did not affect sympathoexcitatory responses induced by hypercapnia.
      Injection of DNQX reduced hypercapnia-induced phrenic activation, whereas MCPG
      did not. In animals with intact carotid chemoreceptors, bilateral injections of
      AP-5 and DNQX in the RTN reduced increases in MAP, sSND and PND amplitude
      produced by intravenous injection of NaCN (50 MUg kg(-1)). Injection of MCPG in
      the RTN did not change responses produced by NaCN. These data indicate that RTN
      ionotropic glutamatergic receptors are involved in the sympathetic and
      respiratory responses produced by central and peripheral chemoreceptor
      activation.

PMID- 21742755
TI  - Do parent protective responses mediate the relation between parent distress and
      child functional disability among children with chronic pain?
AB  - OBJECTIVES: To examine whether protective parent responses mediate the relation
      between parent distress and child functioning. METHODS: At a pain clinic
      evaluation, 157 families participated. Parents completed measures of global
      distress (BSI-18), distress in the context of their child's pain (BAP-PIQ), and
      protective responses to their child's pain. Children completed measures of
      functional disability and pain. RESULTS: BAP-PIQ subscales were significantly
      associated with child functional disability, whereas BSI subscales were
      unrelated. Protective parent responses partially mediated the relation between
      parent distress and child functional disability for depression, anxiety, and
      catastrophizing. However, parent protective behavior fully mediated the
      relationship between parent helplessness and child functional disability,
      indicating that feelings of parent helplessness did not uniquely contribute to
      child functional disability. Discussion Results suggest that when treating youth
      with chronic pain, parental distress in the context of children's pain needs to
      be addressed.

PMID- 21742756
TI  - The effect of a cardiopulmonary bypass system with biocompatible coating on
      fibrinogen levels determined by the TEG--functional fibrinogen method:
      preliminary results.
AB  - When cardiopulmonary bypass (CPB) is used, the blood comes into contact with
      foreign surfaces. To diminish this impact, various types of biocompatibly coated
      surfaces have been developed. The study assessed the effects of heparin-coated
      CPB systems on the level and function of fibrinogen as measured by
      thromboelastography (TEG), as compared with non-coated systems. No statistically
      significant differences between both groups were revealed by comparing paired
      data. In our study, heparin-coated CPB circuits had no significant effect on
      either fibrinogen level or its function.

PMID- 21742757
TI  - Ultra-deep pyrosequencing analysis of the hepatitis B virus preCore region and
      main catalytic motif of the viral polymerase in the same viral genome.
AB  - Hepatitis B virus (HBV) pregenomic RNA contains a hairpin structure (epsilon)
      located in the preCore region, essential for viral replication. epsilon stability
      is enhanced by the presence of preCore variants and epsilon is recognized by the
      HBV polymerase (Pol). Mutations in the retrotranscriptase domain (YMDD) of Pol
      are associated with treatment resistance. The aim of this study was to analyze
      the preCore region and YMDD motif by ultra-deep pyrosequencing (UDPS). To
      evaluate the UDPS error rate, an internal control sequence was inserted in the
      amplicon. A newly developed technique enabled simultaneous analysis of the
      preCore region and Pol in the same viral genome, as well as the conserved
      sequence of the internal control. Nucleotide errors in HindIII yielded a UDPS
      error rate <0.05%. UDPS study confirmed the possibility of simultaneous detection
      of preCore and YMDD mutations, and demonstrated the complexity of the HBV
      quasispecies and cooperation between viruses. Thermodynamic stability of the
      epsilon signal was found to be the main constraint for selecting main preCore
      mutations. Analysis of epsilon-signal variability suggested the essential nature
      of the epsilon structural motif and that certain nucleotides may be involved in
      epsilon signal functions.

PMID- 21742758
TI  - Computational analysis of DNA replicases in double-stranded DNA viruses:
      relationship with the genome size.
AB  - Genome duplication in free-living cellular organisms is performed by DNA
      replicases that always include a DNA polymerase, a DNA sliding clamp and a clamp
      loader. What are the evolutionary solutions for DNA replicases associated with
      smaller genomes? Are there some general principles? To address these questions we
      analyzed DNA replicases of double-stranded (ds) DNA viruses. In the process we
      discovered highly divergent B-family DNA polymerases in phiKZ-like phages and
      remote sliding clamp homologs in Ascoviridae family and Ma-LMM01 phage. The
      analysis revealed a clear dependency between DNA replicase components and the
      viral genome size. As the genome size increases, viruses universally encode their
      own DNA polymerases and frequently have homologs of DNA sliding clamps, which
      sometimes are accompanied by clamp loader subunits. This pattern is highly non
      random. The absence of sliding clamps in large viral genomes usually coincides
      with the presence of atypical polymerases. Meanwhile, sliding clamp homologs, not
      accompanied by clamp loaders, have an elevated positive electrostatic potential,
      characteristic of non-ring viral processivity factors that bind the DNA directly.
      Unexpectedly, we found that similar electrostatic properties are shared by the
      eukaryotic 9-1-1 clamp subunits, Hus1 and, to a lesser extent, Rad9, also
      suggesting the possibility of direct DNA binding.

PMID- 21742759
TI  - Fluorescence protection assay: a novel homogeneous assay platform toward
      development of aptamer sensors for protein detection.
AB  - Development of novel aptamer sensor strategies for rapid and selective assays of
      protein biomarkers plays crucial roles in proteomics and clinical diagnostics.
      Herein, we have developed a novel aptamer sensor strategy for homogeneous
      detection of protein targets based on fluorescence protection assay. This
      strategy is based on our reasoning that interaction of aptamer with its protein
      target may dramatically increase steric hindrance, which protects the
      fluorophore, fluorescein isothiocyannate (FITC), labeled at the binding pocket
      from accessing and quenching by the FITC antibody. The aptamer sensor strategy is
      demonstrated using a model protein target of immunoglobulin E (IgE), a known
      biomarker associated with atopic allergic diseases. The results reveal that the
      aptamer sensor shows substantial (>6-fold) fluorescence enhancement in response
      to the protein target, thereby verifying the mechanism of fluorescence
      protection. Moreover, the aptamer sensor displays improved specificity to other
      co-existing proteins and a desirable dynamic range within the IgE concentration
      from 0.1 to 50 nM with a readily achieved detection limit of 0.1 nM. Because of
      great robustness, easy operation and scalability for parallel assays, the
      developed homogeneous fluorescence protection assay strategy might create a new
      methodology for developing aptamer sensors in sensitive, selective detection of
      proteins.

PMID- 21742760
TI  - Histone modifications influence mediator interactions with chromatin.
AB  - The Mediator complex transmits activation signals from DNA bound transcription
      factors to the core transcription machinery. Genome wide localization studies
      have demonstrated that Mediator occupancy not only correlates with high levels of
      transcription, but that the complex also is present at transcriptionally silenced
      locations. We provide evidence that Mediator localization is guided by an
      interaction with histone tails, and that this interaction is regulated by their
      post-translational modifications. A quantitative, high-density genetic
      interaction map revealed links between Mediator components and factors affecting
      chromatin structure, especially histone deacetylases. Peptide binding assays
      demonstrated that pure wild-type Mediator forms stable complexes with the tails
      of Histone H3 and H4. These binding assays also showed Mediator-histone H4
      peptide interactions are specifically inhibited by acetylation of the histone H4
      lysine 16, a residue critical in transcriptional silencing. Finally, these
      findings were validated by tiling array analysis that revealed a broad
      correlation between Mediator and nucleosome occupancy in vivo, but a negative
      correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16.
      Our studies show that chromatin structure and the acetylation state of histones
      are intimately connected to Mediator localization.

PMID- 21742761
TI  - Structural basis for the biological relevance of the invariant apical stem in
      IRES-mediated translation.
AB  - RNA structure plays a fundamental role in internal initiation of translation.
      Picornavirus internal ribosome entry site (IRES) are long, efficient cis-acting
      elements that recruit the ribosome to internal mRNA sites. However, little is
      known about long-range constraints determining the IRES RNA structure. Here, we
      sought to investigate the functional and structural relevance of the invariant
      apical stem of a picornavirus IRES. Mutation of this apical stem revealed better
      performance of G:C compared with C:G base pairs, demonstrating that the secondary
      structure solely is not sufficient for IRES function. In turn, mutations designed
      to disrupt the stem abolished IRES activity. Lack of tolerance to accept genetic
      variability in the apical stem was supported by the presence of coupled
      covariations within the adjacent stem-loops. SHAPE structural analysis, gel
      mobility-shift and microarrays-based RNA accessibility revealed that the apical
      stem contributes to maintain IRES RNA structure through the generation of distant
      interactions between two adjacent stem-loops. Our results demonstrate that a
      highly interactive structure constrained by distant interactions involving
      invariant G:C base pairs plays a key role in maintaining the RNA conformation
      necessary for IRES-mediated translation.

PMID- 21742762
TI  - Histone variant H3.3 stimulates HSP70 transcription through cooperation with
      HP1gamma.
AB  - Histone variant H3.3 and heterochromatin protein 1gamma (HP1gamma) are two
      functional components of chromatin with role in gene transcription. However, the
      regulations of their dynamics during transcriptional activation and the molecular
      mechanisms underlying their actions remain poorly understood. Here, we provide
      evidence that heat shock-induced transcription of the human HSP70 gene is
      regulated via the coordinated and interdependent action of H3.3 and HP1gamma.
      H3.3 and HP1gamma are rapidly co-enriched at the human HSP70 promoters upon heat
      shock in a manner that closely parallels the initiation of transcription.
      Knockdown of H3.3 prevents the stable recruitment of HP1gamma, inhibits active
      histone modifications, and attenuates HSP70 promoter activity. Likewise,
      knockdown of HP1gamma leads to the decreased levels of H3.3 in the promoter
      regions and the repression of HSP70 genes. HP1gamma selectively recognizes
      particular modification states of H3.3 in the nucleosome for its action.
      Moreover, HP1gamma is overexpressed in three representative cancer cell lines,
      and its knockdown leads to reduction in HSP70 gene transcription and inhibition
      of cancer cell proliferation. We conclude that the physical and functional
      interactions between H3.3 and HP1gamma make a unique contribution to acute HSP70
      transcription and cancer development related to the misregulation of this
      transcription event.

PMID- 21742763
TI  - RNAs synthesized using photocleavable biotinylated nucleotides have dramatically
      improved catalytic efficiency.
AB  - Obtaining homogeneous population of natively folded RNAs is a crippling problem
      encountered when preparing RNAs for structural or enzymatic studies. Most of the
      traditional methods that are employed to prepare large quantities of RNAs involve
      procedures that partially denature the RNA. Here, we present a simple strategy
      using 'click' chemistry to couple biotin to a 'caged' photocleavable (PC)
      guanosine monophosphate (GMP) in high yield. This biotin-PC GMP, accepted by T7
      RNA polymerase, has been used to transcribe RNAs ranging in size from 27 to 527
      nt. Furthermore we show, using an in-gel fluorescence assay, that natively
      prepared 160 and 175 kDa minimal group II intron ribozymes have enhanced
      catalytic activity over the same RNAs, purified via denaturing conditions and
      refolded. We conclude that large complex RNAs prepared by non-denaturing means
      form a homogeneous population and are catalytically more active than those
      prepared by denaturing methods and subsequent refolding; this facile approach for
      native RNA preparation should benefit synthesis of RNAs for biophysical and
      therapeutic applications.

PMID- 21742764
TI  - Thrombosis with inflammatory bowel disease--bleed, clot or break.

PMID- 21742765
TI  - Variation in the MU-opioid receptor gene (OPRM1) moderates the influence of early
      maternal care on fearful attachment.
AB  - There is evidence that both early experience and genetic variation play a role in
      influencing sensitivity to social rejection. In this study, we aimed at
      ascertaining if the A118G polymorphism of the MU-opioid receptor gene (OPRM1)
      moderates the impact of early maternal care on fearful attachment, a personality
      trait strongly related to rejection sensitivity. In 112 psychiatric patients,
      early maternal care and fearful attachment were measured using the Parental
      Bonding Inventory and the Relationship Questionnaire (RQ), respectively. The
      pattern emerging from the RQ data was a crossover interaction between genotype
      and maternal caregiving. Participants expressing the minor 118 G allele had
      similar and relatively high scores on fearful attachment regardless of the
      quality of maternal care. By contrast, early experience made a major difference
      for participants carrying the A/A genotype. Those who recalled higher levels of
      maternal care reported the lowest levels of fearful attachment whereas those who
      recalled lower levels of maternal care scored highest on fearful attachment. Our
      data fit well with the differential susceptibility model which stipulates that
      plasticity genes would make some individuals more responsive than others to the
      negative consequences of adversity and to the benefits of environmental support
      and enrichment.

PMID- 21742766
TI  - Significant vaccination delay can occur even in a community with very high
      vaccination coverage: evidence from Ballabgarh, India.
AB  - BACKGROUND: The current study was undertaken to estimate the delay in vaccination
      for National Immunization Schedule vaccines in under-five children and explore
      causes for this delay. METHODS: The study was carried out in Ballabgarh Health
      and Demographic Surveillance Site in Northern India. It is a secondary data set
      based study of children born between 1991 and 2004. Causes for delay in
      vaccination were explored by informal discussions. RESULTS: Total of 25 517
      children were included in the analysis. Vaccination coverage at 1 year of age was
      high for all National immunization schedule vaccines (78.7% for measles to 97.4%
      for OPV-1). Children for delayed vaccination ranged from 15.9% (95% CI 15.4-16.3)
      for OPV booster to 83.5% (95% CI 83.1-83.9) for OPV-3. Non-availability of
      children was identified as important determinants of the delay. CONCLUSIONS: We
      conclude that focus on 'quantity' in vaccination (high vaccination coverage)
      needs to be supplemented with quality of vaccination (in-time vaccination).

PMID- 21742767
TI  - A comprehensive manually curated reaction map of RANKL/RANK-signaling pathway.
AB  - Receptor activator of nuclear factor-kappa B ligand (RANKL) is a member of tumor
      necrosis factor (TNF) superfamily that plays a key role in the regulation of
      differentiation, activation and survival of osteoclasts and also in tumor cell
      migration and bone metastasis. Osteoclast activation induced by RANKL regulates
      hematopoietic stem cell mobilization as part of homeostasis and host defense
      mechanisms thereby linking regulation of hematopoiesis with bone remodeling.
      Binding of RANKL to its receptor, Receptor activator of nuclear factor-kappa B
      (RANK) activates molecules such as NF-kappa B, mitogen activated protein kinase
      (MAPK), nuclear factor of activated T cells (NFAT) and phosphatidyl 3-kinase
      (PI3K). Although the molecular and cellular roles of these molecules have been
      reported previously, a systematic cataloging of the molecular events induced by
      RANKL/RANK interaction has not been attempted. Here, we present a comprehensive
      reaction map of the RANKL/RANK-signaling pathway based on an extensive manual
      curation of the published literature. We hope that the curated RANKL/RANK
      signaling pathway model would enable new biomedical discoveries, which can
      provide novel insights into disease processes and development of novel
      therapeutic interventions.

PMID- 21742768
TI  - AtIRT1, the primary iron uptake transporter in the root, mediates excess nickel
      accumulation in Arabidopsis thaliana.
AB  - Nickel (Ni) is an essential nutrient for plants, but excessive amounts can be
      toxic. Ni competes with iron (Fe) in vivo, raising the possibility that Ni is
      competitively taken up via the Fe uptake system in plants. Here, we show evidence
      that AtIRT1, the primary Fe(2+) uptake transporter in the root, mediates Ni
      accumulation in Arabidopsis thaliana. In hydroponic cultures, excess Ni exposure
      increased Fe accumulation and the relative transcription level of AtIRT1 in
      roots, indicating that excess Ni induces AtIRT1 expression in roots. An Fe
      deficient treatment increased Ni accumulation in plants, suggesting that excess
      Ni was absorbed via the Fe uptake system, which was induced by Fe starvation.
      Moreover, Ni accumulation under Fe-deficient conditions was markedly lower in
      AtIRT1-defective mutants than in the wild-type, Col-0. Furthermore, AtIRT1 showed
      Ni(2+) uptake activity in a yeast expression system. These data demonstrate that
      AtIRT1 transports Ni(2+) in roots, and strongly suggest that Ni accumulation is
      further accelerated by AtIRT1 that is expressed in response to excess Ni.

PMID- 21742769
TI  - p53-dependent BRCA1 nuclear export controls cellular susceptibility to DNA
      damage.
AB  - Subcellular localization regulates BRCA1 function, and BRCA1 is exported to the
      cytoplasm following DNA damage in a p53-dependent manner. Because more than 50%
      of solid tumors harbor p53 mutations, it is possible that genetically wild-type
      (wt) BRCA1 is functionally abnormal through compromised nuclear-cytoplasmic
      shuttling in sporadic breast cancer patients with dysfunctional p53. In this
      study, we have investigated the mechanisms of p53-dependent BRCA1 subcellular
      distribution and DNA damage-induced nuclear export, as well as the impact on the
      resulting cytotoxic response to therapy in human breast cancer. We first show
      that p53 mediates BRCA1 nuclear export via protein-protein binding, rather than
      by modulation of its transcription. Furthermore, it is the C-terminal (BRCT)
      region of BRCA1 that is critical for its interaction with p53, and p53 may
      promote BRCA1 nuclear export by interrupting the association of BRCA1 with BARD1.
      In sporadic breast cancer specimens, dysfunctional p53 strongly correlates with
      nuclear retention of sequence-verified wt BRCA1. This p53-dependent BRCA1
      shuttling determines cellular susceptibility to DNA damage as augmentation of
      cytosolic BRCA1 significantly enhances cancer cell susceptibility to ionizing
      radiation. Taken together, our data suggest that p53 dysfunction compromises
      nuclear export of wt BRCA1 as a mechanism to increase cellular resistance to DNA
      damage in sporadic breast cancer. We propose that targeting nuclear BRCA1 to the
      cytoplasm may offer a unique strategy to sensitize p53-deficient sporadic breast
      cancers to DNA damage-based therapy.

PMID- 21742770
TI  - STK33 kinase activity is nonessential in KRAS-dependent cancer cells.
AB  - Despite the prevalence of KRAS mutations in human cancers, there remain no
      targeted therapies for treatment. The serine-threonine kinase STK33 has been
      proposed to be required for the survival of mutant KRAS-dependent cell lines,
      suggesting that small molecule kinase inhibitors of STK33 may be useful to treat
      KRAS-dependent tumors. In this study, we investigated the role of STK33 in mutant
      KRAS human cancer cells using RNA interference, dominant mutant overexpression,
      and small molecule inhibitors. As expected, KRAS downregulation decreased the
      survival of KRAS-dependent cells. In contrast, STK33 downregulation or dominant
      mutant overexpression had no effect on KRAS signaling or survival of these cells.
      Similarly, a synthetic lethal siRNA screen conducted in a broad panel of KRAS
      wild-type or mutant cells identified KRAS but not STK33 as essential for
      survival. We also obtained similar negative results using small molecule
      inhibitors of the STK33 kinase identified by high-throughput screening. Taken
      together, our findings refute earlier proposals that STK33 inhibition may be a
      useful therapeutic approach to target human KRAS mutant tumors.

PMID- 21742771
TI  - Comparing signaling networks between normal and transformed hepatocytes using
      discrete logical models.
AB  - Substantial effort in recent years has been devoted to constructing and analyzing
      large-scale gene and protein networks on the basis of "omic" data and literature
      mining. These interaction graphs provide valuable insight into the topologies of
      complex biological networks but are rarely context specific and cannot be used to
      predict the responses of cell signaling proteins to specific ligands or drugs.
      Conversely, traditional approaches to analyzing cell signaling are narrow in
      scope and cannot easily make use of network-level data. Here, we combine network
      analysis and functional experimentation by using a hybrid approach in which
      graphs are converted into simple mathematical models that can be trained against
      biochemical data. Specifically, we created Boolean logic models of immediate
      early signaling in liver cells by training a literature-based prior knowledge
      network against biochemical data obtained from primary human hepatocytes and 4
      hepatocellular carcinoma cell lines exposed to combinations of cytokines and
      small-molecule kinase inhibitors. Distinct families of models were recovered for
      each cell type, and these families clustered topologically into normal and
      diseased sets.

PMID- 21742772
TI  - IL-12 release by engineered T cells expressing chimeric antigen receptors can
      effectively Muster an antigen-independent macrophage response on tumor cells that
      have shut down tumor antigen expression.
AB  - During malignant progression cancer cells tend to lose cell surface expression of
      MHC and other immune antigens, making them invisible to cytotoxic T cells and
      therefore inaccessible to tumor antigen-directed immunotherapy. Moreover, cancer
      cell variants that have lost antigen expression frequently contribute to deadly
      tumor relapses that occur following treatments that had been initially effective.
      In an effort to destroy antigen-loss cancer cells in tumors, we created a
      strategy that combines a chimeric antigen receptor (CAR)-redirected T-cell attack
      with an engineered local release of the cytokine interleukin 12 (IL-12), which
      recruits and reinforces macrophage function. Cytotoxic T cells were engineered to
      release inducible IL-12 upon CAR engagement in the tumor lesion, resulting in
      destruction of antigen-loss cancer cells that would normally escape. Importantly,
      elimination of the antigen-loss cancer cells was accompanied by an accumulation
      of activated macrophages that was critical to the antitumor response, because
      removing the macrophages abolished the response and restoring them reengaged it.
      Neutralizing TNF-alpha also abrogated the elimination of antigen-loss cancer
      cells, implying this proinflammatory factor in the process. Taken together, our
      results show how IL-12 supplementation by CAR T cells can target otherwise
      inaccessible tumor lesions, in a manner associated with reduced systemic
      toxicity, by recruiting and activating innate immune cells for a proinflammatory
      response.

PMID- 21742773
TI  - p53-dependent regulation of mitochondrial energy production by the RelA subunit
      of NF-kappaB.
AB  - Aberrant activity of the nuclear factor kappaB (NF-kappaB) transcription factor
      family, which regulates cellular responses to stress and infection, is associated
      with many human cancers. In this study, we define a function of NF-kappaB in
      regulation of cellular respiration that is dependent upon the tumor suppressor
      p53. Translocation of the NF-kappaB family member RelA to mitochondria was
      inhibited by p53 by blocking an essential interaction with the HSP Mortalin.
      However, in the absence of p53, RelA was transported into the mitochondria and
      recruited to the mitochondrial genome where it repressed mitochondrial gene
      expression, oxygen consumption, and cellular ATP levels. We found mitochondrial
      RelA function to be dependent on its conserved C-terminal transactivation domain
      and independent of its sequence-specific DNA-binding ability, suggesting that its
      function in this setting was mediated by direct interaction with mitochondrial
      transcription factors. Taken together, our findings uncover a new mechanism
      through which RelA can regulate mitochondrial function, with important
      implications for how NF-kappaB activity and loss of p53 can contribute to changes
      in tumor cell metabolism and energy production.

PMID- 21742774
TI  - CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival
      in an immunocompetent mouse model of ovarian cancer.
AB  - The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human
      cancers, including ovarian cancer, in which they are associated with disease
      progression at the levels of tumor cell proliferation, invasion, and
      angiogenesis. Here, we used an immunocompetent mouse model of intraperitoneal
      papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4
      axis in ovarian cancer has multimodal effects on tumor pathogenesis associated
      with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1
      cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in
      vitro, and tumor growth in vivo. Similarly, treatment of BR5-1-derived tumors
      with AMD3100, a selective CXCR4 antagonist, resulted in increased tumor apoptosis
      and necrosis, reduction in intraperitoneal dissemination, and selective reduction
      of intratumoral FoxP3(+) regulatory T cells (Treg). Compared with controls, CXCR4
      blockade greatly increased T-cell-mediated antitumor immune responses, conferring
      a significant survival advantage to AMD3100-treated mice. In addition, the
      selective effect of CXCR4 antagonism on intratumoral Tregs was associated with
      both higher CXCR4 expression and increased chemotactic responses to CXCL12, a
      finding that was also confirmed in a melanoma model. Together, our findings
      reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian
      cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4
      as a therapeutic target in this disease.

PMID- 21742775
TI  - Evolutionary consequences of introgression at M7 lysin, a gamete recognition
      locus, following secondary contact between blue mussel species.
AB  - Hybridizing populations of blue mussels, Mytilus edulis and Mytilus trossulus, in
      Cobscook Bay (eastern Maine) have been used by our laboratory to study the
      evolution of gamete incompatibility and molecular evolution of the vitelline coat
      lysin proteins expressed in sperm. The M7 lysin locus has been the most studied
      of the three lysins, but evidence for positive selection necessary to help
      confirm its role in gamete recognition in western Atlantic hybrid zones is
      contradictory. We developed an alternative test, based on rates of introgression
      at M7 lysin. Contrary to expectations, introgression at this locus is much higher
      (instead of much lower) than is introgression at neutral markers. In this
      article, we present simulations, constructed using synthetic populations of
      combinations of admixed genotypes, representing various hybrid offspring
      categories. Simulations produced variation in introgression across loci, but did
      not generate the massive introgression at M7 lysin observed in natural
      populations in Cobscook Bay. We consider these results in the context of
      selection operating on gamete recognition loci, both within and between species,
      during the third stage of allopatric speciation in Mytilus.

PMID- 21742776
TI  - Speciation in red algae: members of the Ceramiales as model organisms.
AB  - Red algae (Rhodophyta) are an ancient group with unusual morphological,
      biochemical, and life-history features including a complete absence of flagella.
      Although the red algae present many opportunities for studying speciation, this
      has rarely been explicitly addressed. Here, we examine an aspect of paternal gene
      flow by determining fertilization success of female Neosiphonia harveyi
      (Ceramiales), which retains a morphological record of all successful and
      unsuccessful female gametes. High fertilization rates were observed except when
      there were no males at all within the tidepool, or in a submerged marina
      environment. Small numbers of reproductive males were able to saturate
      fertilization rates, suggesting that limited availability of sperm may be less
      significant in red algae than previously thought. In another member of the
      Ceramiales, Antithamnion, relatively large chromosomes permit karyological
      identification of polyploids. The Western Pacific species Antithamnion sparsum is
      closely related to the diploid species Antithamnion defectum, known only from the
      Eastern Pacific, and appears to have evolved from it. Molecular evidence suggests
      that A. sparsum is an autopolyploid, and that the European species known as
      Antithamnion densum is divergent from the A. sparsum/defectum complex.

PMID- 21742777
TI  - Mammalian masticatory muscles: homology, nomenclature, and diversification.
AB  - There is a deep and rich literature of comparative studies of jaw muscles in
      mammals but no recent analyses employ modern phylogenetic techniques to better
      understand evolutionary changes that have occurred in these muscles. In order to
      fully develop and utilize the Feeding Experiments End-user Database (FEED), we
      are constructing a comprehensive ontology of mammalian jaw muscles. This process
      has led to a careful consideration of nomenclature and homologies of the muscles
      and their constituent parts. Precise determinations of muscle attachments have
      shown that muscles with similar names are not necessarily homologous. Using new
      anatomical descriptions derived from the literature, we defined character states
      for the jaw muscles in diverse mammalian species. We then mapped those characters
      onto a recent phylogeny of mammals with the aid of the Mesquite software package.
      Our data further elucidate how muscle groups associated with the feeding
      apparatus differ and have become highly specialized in certain mammalian orders,
      such as Rodentia, while remaining conserved in other orders. We believe that
      careful naming of muscles and statistical analyses of their distributions among
      mammals, in association with the FEED database, will lead to new, significant
      insights into the functional, structural, and evolutionary morphology of the jaw
      muscles.

PMID- 21742778
TI  - Evaporative water loss is a plausible explanation for mortality of bats from
      white-nose syndrome.
AB  - White-nose syndrome (WNS) has caused alarming declines of North American bat
      populations in the 5 years since its discovery. Affected bats appear to starve
      during hibernation, possibly because of disruption of normal cycles of torpor and
      arousal. The importance of hydration state and evaporative water loss (EWL) for
      influencing the duration of torpor bouts in hibernating mammals recently led to
      "the dehydration hypothesis," that cutaneous infection of the wing membranes of
      bats with the fungus Geomyces destructans causes dehydration which in turn,
      increases arousal frequency during hibernation. This hypothesis predicts that
      uninfected individuals of species most susceptible to WNS, like little brown bats
      (Myotis lucifugus), exhibit high rates of EWL compared to less susceptible
      species. We tested the feasibility of this prediction using data from the
      literature and new data quantifying EWL in Natterer's bats (Myotis nattereri), a
      species that is, like other European bats, sympatric with G. destructans but does
      not appear to suffer significant mortality from WNS. We found that little brown
      bats exhibited significantly higher rates of normothermic EWL than did other bat
      species for which comparable EWL data are available. We also found that
      Natterer's bats exhibited significantly lower rates of EWL, in both wet and dry
      air, compared with values predicted for little brown bats exposed to identical
      relative humidity (RH). We used a population model to show that the increase in
      EWL required to cause the pattern of mortality observed for WNS-affected little
      brown bats was small, equivalent to a solitary bat hibernating exposed to RH of
      ~95%, or clusters hibernating in ~87% RH, as opposed to typical near-saturation
      conditions. Both of these results suggest the dehydration hypothesis is plausible
      and worth pursuing as a possible explanation for mortality of bats from WNS.

PMID- 21742779
TI  - Chelation of lysosomal iron protects dopaminergic SH-SY5Y neuroblastoma cells
      from hydrogen peroxide toxicity by precluding autophagy and Akt
      dephosphorylation.
AB  - In human neuroblastoma SH-SY5Y cells, hydrogen peroxide (H(2)O(2), 200MUM)
      rapidly (< 5 min) induced autophagy, as shown by processing and vacuolar
      relocation of light chain 3(LC3). Accumulation of autophagosome peaked at 30 min
      of H(2)O(2) exposure. The continuous presence of H(2)O(2) eventually (at > 60
      min) caused autophagy-dependent annexin V-positive cell death. However, the cells
      exposed to H(2)O(2) for 30 min and then cultivated in fresh medium could recover
      and grow, despite ongoing autophagy. H(2)O(2) rapidly (5 min) triggered the
      formation of dichlorofluorescein-sensitive HO(.)-free radicals within
      mitochondria, whereas the mitochondria-associated oxidoradicals revealed by
      MitoSox (O(2)(.-)) became apparent after 30 min of exposure to H(2)O(2). 3
      Methyladenine inhibited autophagy and cell death, but not the generation of
      HO(.). Genetic silencing of beclin-1 prevented bax- and annexin V-positive cell
      death induced by H(2)O(2), confirming the involvement of canonical autophagy in
      peroxide toxicity. The lysosomotropic iron chelator deferoxamine (DFO) prevented
      the mitochondrial generation of both HO(.) and O(2)(.-) and suppressed the
      induction of autophagy and of cell death by H(2)O(2). Upon exposure to H(2)O(2),
      Akt was intensely phosphorylated in the first 30 min, concurrently with mammalian
      target of rapamycin inactivation and autophagy, and it was dephosphorylated at 2
      h, when > 50% of the cells were dead. DFO did not impede Akt phosphorylation,
      which therefore was independent of reactive oxygen species (ROS) generation but
      inhibited Akt dephosphorylation. In conclusion, exogenous H(2)O(2) triggers two
      parallel independent pathways, one leading to autophagy and autophagy-dependent
      apoptosis, the other to transient Akt phosphorylation, and both are inhibited by
      DFO. The present work establishes HO(.) as the autophagy-inducing ROS and
      highlights the need for free lysosomal iron for its production within
      mitochondria in response to hydrogen peroxide.

PMID- 21742780
TI  - NADPH oxidase activation is required in reactive oxygen species generation and
      cell transformation induced by hexavalent chromium.
AB  - Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the
      incidence of lung cancer. Although overproduction of reactive oxygen species
      (ROS) has been suggested to play a major role in its carcinogenicity, the
      mechanisms of Cr(VI)-induced ROS production remain unclear. In this study, we
      investigated the role of NADPH oxidase (NOX), one of the major sources of
      cellular ROS, in Cr(VI)-induced oxidative stress and carcinogenesis. We found
      that short-term exposure to Cr(VI) (2MUM) resulted in a rapid increase in ROS
      generation in Beas-2B cells, and concomitantly increased NOX activity and
      expression of NOX members (NOX1-3 and NOX5) and subunits (p22(phox), p47(phox),
      p40(phox), and p67(phox)). Cr(VI) also induced phosphorylation of p47(phox) and
      membrane translocation of p47(phox) and p67(phox), further confirming NOX
      activation. Knockdown of p47(phox) with a short hairpin RNA attenuated the ROS
      production induced by Cr(VI). Chronic exposure (up to 3 months) to low doses of
      Cr(VI) (0.125, 0.25, and 0.5MUM) also promoted ROS generation and the expression
      of NOX subunits, such as p47(phox) and p67(phox), but inhibited the expression of
      main antioxidant enzymes, such as superoxidase dismutase (SOD) and glutathione
      peroxidase (GPx). Chronic Cr(VI) exposure resulted in transformation of Beas-2B
      cells, increasing cell proliferation, anchorage independent growth in soft agar,
      and forming aggressive tumors in nude mice. Stable knockdown of p47(phox) or
      overexpression of SOD1, SOD2, or catalase (CAT) eliminated Cr(VI)-induced
      malignant transformation. Our results suggest that NOX plays an important role in
      Cr(VI)-induced ROS generation and carcinogenesis.

PMID- 21742781
TI  - Cross talk between keratinocytes and dendritic cells: impact on the prediction of
      sensitization.
AB  - Understanding the mechanistic aspects involved in sensitization by chemicals will
      help to develop relevant preventive strategies. Many potential sensitizers are
      not directly immunogenic but require activation outside or inside the skin by
      nonenzymatic oxidation (prehaptens) or metabolic transformation (prohaptens)
      prior to being able to induce an immune response. This necessary activation step
      has not yet been actively integrated into a cell line-based prediction approach.
      We cocultured HaCaT keratinocytes with THP-1 as dendritic cell-like cells
      allowing intercellular interactions. The sensitizing potential was determined by
      analyzing differences in the expression of CD86, CD40, and CD54 on cocultured THP
      1 cells. This new assay setup allowed (1) to distinguish irritants from allergens
      without influencing cell viability and (2) to discriminate pre/prohaptens from
      haptens. Under coculture conditions, the prohaptens eugenol, 2-methoxy-4
      methylphenol, and benzo[a]pyrene induced a significantly higher upregulation of
      CD86 expression on THP-1. In agreement with the hapten concept, responses to 2,4
      dinitrochlorobenzene, Bandrowski's base, and the prehapten isoeugenol were not
      significantly modified. Inhibition of cytochrome P450 or NAD(P)H:quinone
      oxidoreductase (NQO1) activity reduced the prohapten-mediated upregulation of
      CD86 on cocultured THP-1 cells. This coculture assay allowing cross talk between
      HaCaT and THP-1 cells appears to be suitable for the detection of prohaptens, is
      reproducible, easy to perform, and avoids donor variations. In addition, this
      assay is a promising approach to understand the impact of cross talk on the
      prediction of sensitization and once established may be integrated in a future in
      vitro toolbox to detect potential skin sensitizers and may thus contribute to
      reduce animal testing.

PMID- 21742782
TI  - Acetyl tributyl citrate, the most widely used phthalate substitute plasticizer,
      induces cytochrome p450 3a through steroid and xenobiotic receptor.
AB  - Steroid and xenobiotic receptor (SXR) is activated by endogenous and exogenous
      chemicals including steroids, bile acids, and prescription drugs. SXR is highly
      expressed in the liver and intestine, where it regulates cytochrome P450 3A4
      (CYP3A4), which in turn controls xenobiotic and endogenous steroid hormone
      metabolism. However, it is unclear whether Food and Drug Administration (FDA)
      approved plasticizers exert such activity. In the present study, we evaluated the
      effects of FDA-approved plasticizers on SXR-mediated transcription in vitro by
      luciferase reporter, SXR-coactivator interaction, quantitative real-time PCR
      analysis of CYP3A4 expression, CYP3A4 enzyme activity assays, and SXR knockdown.
      Rats, treated with gavage and intraperitoneal injection of compounds, were
      examined for CYP3A1 expression in vivo. We found that four of eight FDA-approved
      plasticizers increased SXR-mediated transcription. In particular, acetyl tributyl
      citrate (ATBC), an industrial plasticizer widely used in products such as food
      wrap, vinyl toys, and pharmaceutical excipients, strongly activated human and rat
      SXR. ATBC increased CYP3A4 messenger RNA (mRNA) levels and enzyme activity in the
      human intestinal cells but not in human liver cells. Similarly, CYP3A1 mRNA
      levels were increased in the intestine but not the liver of ATBC-treated rats.
      These in vitro and in vivo results suggest that ATBC specifically induces CYP3A
      in the intestine by activating SXR. We suggest that ATBC-containing products be
      used cautiously because they may alter metabolism of endogenous steroid hormones
      and prescription drugs.

PMID- 21742783
TI  - Cigarette smoke components induce matrix metalloproteinase-1 in aortic
      endothelial cells through inhibition of mTOR signaling.
AB  - Smoking is a major risk factor for heart disease, but the molecular effects of
      cigarette smoke on vascular cells are poorly understood. In this study, we
      demonstrate that matrix metalloproteinase-1 (MMP-1), a collagenase expressed in
      atherosclerosis and aneurysms but not in the normal vessel wall, is induced in
      the aortic endothelium of rabbits exposed to cigarette smoke. In vitro cigarette
      smoke extract (CSE) and one of its components, acrolein, inhibit the mammalian
      target of rapamycin (mTOR)/p70S6K pathway in human endothelial cells, and
      chemical inhibition of this pathway by rapamycin resulted in elevated MMP-1.
      Moreover, the tissue inhibitor of metalloproteases-3 (TIMP-3), a major regulator
      of angiogenesis, is significantly downregulated in aortic endothelial cells
      treated with CSE, acrolein, or rapamycin. These data indicate that inhibition of
      mTOR by cigarette smoke components is a key event in the modulation of
      endothelial MMP-1 and TIMP-3 expression. Our study suggests that circulating
      smoke components, including acrolein, contribute to vascular diseases through
      enhanced MMP-1 and decreased TIMP-3 secretion in the endothelium, potentially
      leading to impaired angiogenesis, matrix disruption, and vessel injury.

PMID- 21742784
TI  - The protective effect of prolyl-hydroxylase inhibition against renal ischaemia
      requires application prior to ischaemia but is superior to EPO treatment.
AB  - BACKGROUND: Inhibition of the HIF regulating prolyl hydroxylation domain (PHDs)
      proteins prior to renal injury (preconditioning) has been shown to protect the
      kidney via activation of hypoxia-inducible transcription factors (HIF).
      Application of erythropoietin (EPO), one of the HIF target genes, has also been
      shown to be nephroprotective, and it remains unclear to what extent the effect of
      HIF induction is mediated by EPO. It is also unknown whether HIF activation after
      the onset of ischaemia (postconditioning) is still able to protect the kidney.
      METHODS: Using a rat model of renal ischaemia-reperfusion injury, animals were
      treated with the PHD inhibitor (PHD-I) 2-(1-chloro-4-hydroxyisoquinoline-3
      carboxamido) acetate (ICA), vehicle (Veh) or recombinant human EPO (300 IU/kg) 6
      h (ICA or Veh) or 30 min (EPO) prior to ischaemia (preconditioning) or with ICA
      prior to reperfusion (postconditioning). Renal function was assessed at baseline,
      24 h and 72 h. After 72 h, kidneys were processed for histology and morphometric
      analysis. HIF immunohistochemistry and real-time polymerase chain reaction for
      HIF target genes, including EPO, were performed to evaluate ICA effects. RESULTS:
      ICA treatment resulted in stabilization of HIF-1alpha and -2alpha and up
      regulation of HIF target genes in a dose-dependent manner. Preconditional
      activation of HIF by ICA significantly improved serum creatinine levels and renal
      morphology in comparison to Veh (P < 0.05), while postconditional ICA treatment
      was ineffective. EPO therapy improved tissue morphology but had no impact on the
      course of serum creatinine. CONCLUSION: These findings are in line with the
      concept that PHD-Is exert their protective effects through accumulation of HIF
      target gene products, with time requirements for increased transcription and
      translation of HIF-dependent genes, and suggest that their renoprotective effect
      is not predominately mediated by EPO.

PMID- 21742785
TI  - Cancer induction caused by radiation due to computed tomography: a critical note.
AB  - The considerable rise of computed tomography (CT) procedures over the past few
      decades has urged responsible authorities and researchers to evaluate the risk of
      carcinogenesis in the population in relation to the radiation dose delivered to
      the patient. A single patient undergoing CT may receive a radiation equivalent
      dose that varies between about 2 mSv (head ) to about 20 mSv (CT-based coronary
      angiography). Whereas the latter represents a substantial dose delivered to one
      patient it is, however, population-wise far below the area of the so-called low
      doses, i.e. 50 mSv in children and 100 mSv in adults. While at effective doses
      above 50 mSv the risk of cancer induction increases linearly with dose, this dose
      response relation has not been demonstrated at doses below 50 mSv. Below 50 mSv
      no convincing epidemiological evidence for cancer risk exists. Calculations on
      this risk are based on scientifically questionable, if not invalid,
      extrapolations of data from higher doses. However, the failure to demonstrate
      that a risk of cancer exists does not mean that there is no risk. This paper
      summarizes the data mentioned in various articles from recent literature
      discussing cancer risks due to CT and puts the results of these studies in
      perspective of current scientific knowledge in the field of radiation protection.
      For this we follow the lead of the ICRP and UNSCEAR. Furthermore, we review the
      strategies and efforts of various national and international bodies and
      manufacturers of CT apparatus to lower the radiation dose to the patient.

PMID- 21742786
TI  - Utility of time-resolved three-dimensional magnetic resonance digital subtraction
      angiography without contrast material for assessment of intracranial dural
      arterio-venous fistula.
AB  - BACKGROUND: Intracranial dural arteriovenous fistula (DAVF) is an arteriovenous
      shunting disease of the dura. Magnetic resonance angiography (MRA) is expected to
      be a safer alternative method in evaluation of DAVF, compared with invasive intra
      arterial digital subtraction angiography (IADSA). PURPOSE: To evaluate the
      diagnostic use of time-spatial labeling inversion pulse (Time-SLIP) three
      dimensional (3D) magnetic resonance digital subtraction angiography (MRDSA)
      without contrast material in six patients with DAVF. MATERIAL AND METHODS: Images
      for 3D time-of-flight MRA, which has been a valuable tool for the diagnosis of
      DAVF but provide little or less hemodynamic information, and Time-SLIP 3D MRDSA,
      were acquired for each patient. The presence, side, and grade of the disease were
      evaluated according to IADSA. RESULTS: In all patients, the presence and side of
      the DAVF were correctly identified by both 3D time-of-flight MRA and Time-SLIP 3D
      MRDSA. Cortical reflux present in a patient with a grade 2b DAVF was not detected
      by Time-SLIP 3D MRDSA, when compared with IADSA findings. CONCLUSION: Time-SLIP
      3D MRDSA provides hemodynamic information without contrast material and is a
      useful complementary tool for diagnosis of DAVF.

PMID- 21742787
TI  - MR staging accuracy for endometrial cancer based on the new FIGO stage.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been frequently used to
      determine a preoperative treatment plan for gynecologic cancers. However, the MR
      accuracy for staging an endometrial cancer is not satisfactory based on the old
      FIGO staging system. PURPOSE: To evaluate MR accuracy for staging endometrial
      cancer using the new FIGO staging system. MATERIAL AND METHODS: Between January
      2005 and May 2009, 199 women underwent surgery due to endometrial cancer. In each
      patient, an endometrial cancer was staged using MR findings based on the old FIGO
      staging system and then repeated according to the new FIGO staging system for
      comparison. Histopathologic findings were used as a standard of reference.
      RESULTS: The accuracy of MRI in the staging of endometrial carcinoma stage I, II,
      III, and IV using the old FIGO staging system were 80% (159/199), 89% (178/199),
      90% (179/199), and 99% (198/199), respectively, compared to 87% (174/199), 97%
      (193/199), 90% (179/199), and 99% (198/199), respectively, when using the new
      FIGO staging criteria. The overall MR accuracy of the old and new staging systems
      were 51% (101/199) and 81% (161/199), respectively. CONCLUSION: MRI has become a
      more useful tool in the preoperative staging of endometrial cancers using the new
      FIGO staging system compared to the old one with increased accuracy.

PMID- 21742788
TI  - Islet amyloid polypeptide, islet amyloid, and diabetes mellitus.
AB  - Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory
      products of beta-cells of the pancreatic islets of Langerhans. It is a regulatory
      peptide with putative function both locally in the islets, where it inhibits
      insulin and glucagon secretion, and at distant targets. It has binding sites in
      the brain, possibly contributing also to satiety regulation and inhibits gastric
      emptying. Effects on several other organs have also been described. IAPP was
      discovered through its ability to aggregate into pancreatic islet amyloid
      deposits, which are seen particularly in association with type 2 diabetes in
      humans and with diabetes in a few other mammalian species, especially monkeys and
      cats. Aggregated IAPP has cytotoxic properties and is believed to be of critical
      importance for the loss of beta-cells in type 2 diabetes and also in pancreatic
      islets transplanted into individuals with type 1 diabetes. This review deals both
      with physiological aspects of IAPP and with the pathophysiological role of
      aggregated forms of IAPP, including mechanisms whereby human IAPP forms toxic
      aggregates and amyloid fibrils.

PMID- 21742789
TI  - MicroRNAs in development and disease.
AB  - MicroRNAs (miRNAs) are a class of posttranscriptional regulators that have
      recently introduced an additional level of intricacy to our understanding of gene
      regulation. There are currently over 10,000 miRNAs that have been identified in a
      range of species including metazoa, mycetozoa, viridiplantae, and viruses, of
      which 940, to date, are found in humans. It is estimated that more than 60% of
      human protein-coding genes harbor miRNA target sites in their 3' untranslated
      region and, thus, are potentially regulated by these molecules in health and
      disease. This review will first briefly describe the discovery, structure, and
      mode of function of miRNAs in mammalian cells, before elaborating on their roles
      and significance during development and pathogenesis in the various mammalian
      organs, while attempting to reconcile their functions with our existing knowledge
      of their targets. Finally, we will summarize some of the advances made in
      utilizing miRNAs in therapeutics.

PMID- 21742791
TI  - Voltage fluctuations in neurons: signal or noise?
AB  - Noise and variability are fundamental companions to ion channels and synapses and
      thus inescapable elements of brain function. The overriding unresolved issue is
      to what extent noise distorts and limits signaling on one hand and at the same
      time constitutes a crucial and fundamental enrichment that allows and facilitates
      complex adaptive behavior in an unpredictable world. Here we review the growing
      experimental evidence that functional network activity is associated with intense
      fluctuations in membrane potential and spike timing. We trace origins and
      consequences of noise and variability. Finally, we discuss noise-free neuronal
      signaling and detrimental and beneficial forms of noise in large-scale functional
      neural networks. Evidence that noise and variability in some cases go hand in
      hand with behavioral variability and increase behavioral choice, richness, and
      adaptability opens new avenues for future studies.

PMID- 21742792
TI  - Factor XIII: a coagulation factor with multiple plasmatic and cellular functions.
AB  - Factor XIII (FXIII) is unique among clotting factors for a number of reasons: 1)
      it is a protransglutaminase, which becomes activated in the last stage of
      coagulation; 2) it works on an insoluble substrate; 3) its potentially active
      subunit is also present in the cytoplasm of platelets, monocytes, monocyte
      derived macrophages, dendritic cells, chondrocytes, osteoblasts, and osteocytes;
      and 4) in addition to its contribution to hemostasis, it has multiple extra- and
      intracellular functions. This review gives a general overview on the structure
      and activation of FXIII as well as on the biochemical function and downregulation
      of activated FXIII with emphasis on new developments in the last decade. New
      aspects of the traditional functions of FXIII, stabilization of fibrin clot, and
      protection of fibrin against fibrinolysis are summarized. The role of FXIII in
      maintaining pregnancy, its contribution to the wound healing process, and its
      proangiogenic function are reviewed in details. Special attention is given to
      new, less explored, but promising fields of FXIII research that include
      inhibition of vascular permeability, cardioprotection, and its role in cartilage
      and bone development. FXIII is also considered as an intracellular enzyme; a
      separate section is devoted to its intracellular activation, intracellular
      action, and involvement in platelet, monocyte/macrophage, and dendritic cell
      functions.

PMID- 21742790
TI  - CaMKII in the cardiovascular system: sensing redox states.
AB  - The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII)
      is now recognized to play a central role in pathological events in the
      cardiovascular system. CaMKII has diverse downstream targets that promote
      vascular disease, heart failure, and arrhythmias, so improved understanding of
      CaMKII signaling has the potential to lead to new therapies for cardiovascular
      disease. CaMKII is a multimeric serine-threonine kinase that is initially
      activated by binding calcified calmodulin (Ca(2+)/CaM). Under conditions of
      sustained exposure to elevated Ca(2+)/CaM, CaMKII transitions into a Ca(2+)/CaM
      autonomous enzyme by two distinct but parallel processes. Autophosphorylation of
      threonine-287 in the CaMKII regulatory domain "traps" CaMKII into an open
      configuration even after Ca(2+)/CaM unbinding. More recently, our group
      identified a pair of methionines (281/282) in the CaMKII regulatory domain that
      undergo a partially reversible oxidation which, like autophosphorylation,
      prevents CaMKII from inactivating after Ca(2+)/CaM unbinding. Here we review
      roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII
      may act as a transduction signal to connect pro-oxidant conditions into specific
      downstream pathological effects that are relevant to rare and common forms of
      cardiovascular disease.

PMID- 21742793
TI  - Physiological relevance of cell cycle kinases.
AB  - The basic biology of the cell division cycle and its control by protein kinases
      was originally studied through genetic and biochemical studies in yeast and other
      model organisms. The major regulatory mechanisms identified in this pioneer work
      are conserved in mammals. However, recent studies in different cell types or
      genetic models are now providing a new perspective on the function of these major
      cell cycle regulators in different tissues. Here, we review the physiological
      relevance of mammalian cell cycle kinases such as cyclin-dependent kinases
      (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1,
      BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek
      proteins, or Mastl and their implications in development, tissue homeostasis, and
      human disease. Among these functions, the control of self-renewal or asymmetric
      cell division in stem/progenitor cells and the ability to regenerate injured
      tissues is a central issue in current research. In addition, many of these
      proteins play previously unexpected roles in metabolism, cardiovascular function,
      or neuron biology. The modulation of their enzymatic activity may therefore have
      multiple therapeutic benefits in human disease.

PMID- 21742794
TI  - The dynamic modulation of GABA(A) receptor trafficking and its role in regulating
      the plasticity of inhibitory synapses.
AB  - Inhibition in the adult mammalian central nervous system (CNS) is mediated by
      gamma-aminobutyric acid (GABA). The fast inhibitory actions of GABA are mediated
      by GABA type A receptors (GABA(A)Rs); they mediate both phasic and tonic
      inhibition in the brain and are the principle sites of action for anticonvulsant,
      anxiolytic, and sedative-hypnotic agents that include benzodiazepines,
      barbiturates, neurosteroids, and some general anesthetics. GABA(A)Rs are
      heteropentameric ligand-gated ion channels that are found concentrated at
      inhibitory postsynaptic sites where they mediate phasic inhibition and at
      extrasynaptic sites where they mediate tonic inhibition. The efficacy of
      inhibition and thus neuronal excitability is critically dependent on the
      accumulation of specific GABA(A)R subtypes at inhibitory synapses. Here we
      evaluate how neurons control the number of GABA(A)Rs on the neuronal plasma
      membrane together with their selective stabilization at synaptic sites. We then
      go on to examine the impact that these processes have on the strength of synaptic
      inhibition and behavior.

PMID- 21742797
TI  - A gene expression signature from peripheral whole blood for stage I lung
      adenocarcinoma.
AB  - Affordable early screening in subjects with high risk of lung cancer has great
      potential to improve survival from this deadly disease. We measured gene
      expression from lung tissue and peripheral whole blood (PWB) from adenocarcinoma
      cases and controls to identify dysregulated lung cancer genes that could be
      tested in blood to improve identification of at-risk patients in the future.
      Genome-wide mRNA expression analysis was conducted in 153 subjects (73
      adenocarcinoma cases, 80 controls) from the Environment And Genetics in Lung
      cancer Etiology study using PWB and paired snap-frozen tumor and noninvolved lung
      tissue samples. Analyses were conducted using unpaired t tests, linear mixed
      effects, and ANOVA models. The area under the receiver operating characteristic
      curve (AUC) was computed to assess the predictive accuracy of the identified
      biomarkers. We identified 50 dysregulated genes in stage I adenocarcinoma versus
      control PWB samples (false discovery rate <=0.1, fold change >=1.5 or <=0.66).
      Among them, eight (TGFBR3, RUNX3, TRGC2, TRGV9, TARP, ACP1, VCAN, and TSTA3)
      differentiated paired tumor versus noninvolved lung tissue samples in stage I
      cases, suggesting a similar pattern of lung cancer-related changes in PWB and
      lung tissue. These results were confirmed in two independent gene expression
      analyses in a blood-based case-control study (n = 212) and a tumor-nontumor
      paired tissue study (n = 54). The eight genes discriminated patients with lung
      cancer from healthy controls with high accuracy (AUC = 0.81, 95% CI = 0.74-0.87).
      Our finding suggests the use of gene expression from PWB for the identification
      of early detection markers of lung cancer in the future.

PMID- 21742796
TI  - Normalization of the vasculature for treatment of cancer and other diseases.
AB  - New vessel formation (angiogenesis) is an essential physiological process for
      embryologic development, normal growth, and tissue repair. Angiogenesis is
      tightly regulated at the molecular level. Dysregulation of angiogenesis occurs in
      various pathologies and is one of the hallmarks of cancer. The imbalance of pro-
      and anti-angiogenic signaling within tumors creates an abnormal vascular network
      that is characterized by dilated, tortuous, and hyperpermeable vessels. The
      physiological consequences of these vascular abnormalities include temporal and
      spatial heterogeneity in tumor blood flow and oxygenation and increased tumor
      interstitial fluid pressure. These abnormalities and the resultant
      microenvironment fuel tumor progression, and also lead to a reduction in the
      efficacy of chemotherapy, radiotherapy, and immunotherapy. With the discovery of
      vascular endothelial growth factor (VEGF) as a major driver of tumor
      angiogenesis, efforts have focused on novel therapeutics aimed at inhibiting VEGF
      activity, with the goal of regressing tumors by starvation. Unfortunately,
      clinical trials of anti-VEGF monotherapy in patients with solid tumors have been
      largely negative. Intriguingly, the combination of anti-VEGF therapy with
      conventional chemotherapy has improved survival in cancer patients compared with
      chemotherapy alone. These seemingly paradoxical results could be explained by a
      "normalization" of the tumor vasculature by anti-VEGF therapy. Preclinical
      studies have shown that anti-VEGF therapy changes tumor vasculature towards a
      more "mature" or "normal" phenotype. This "vascular normalization" is
      characterized by attenuation of hyperpermeability, increased vascular pericyte
      coverage, a more normal basement membrane, and a resultant reduction in tumor
      hypoxia and interstitial fluid pressure. These in turn can lead to an improvement
      in the metabolic profile of the tumor microenvironment, the delivery and efficacy
      of exogenously administered therapeutics, the efficacy of radiotherapy and of
      effector immune cells, and a reduction in number of metastatic cells shed by
      tumors into circulation in mice. These findings are consistent with data from
      clinical trials of anti-VEGF agents in patients with various solid tumors. More
      recently, genetic and pharmacological approaches have begun to unravel some other
      key regulators of vascular normalization such as proteins that regulate tissue
      oxygen sensing (PHD2) and vessel maturation (PDGFRbeta, RGS5, Ang1/2, TGF-beta).
      Here, we review the pathophysiology of tumor angiogenesis, the molecular
      underpinnings and functional consequences of vascular normalization, and the
      implications for treatment of cancer and nonmalignant diseases.

PMID- 21742798
TI  - Quantitative proteomic analyses of human cytomegalovirus-induced restructuring of
      endoplasmic reticulum-mitochondrial contacts at late times of infection.
AB  - Endoplasmic reticulum-mitochondrial contacts, known as mitochondria-associated
      membranes, regulate important cellular functions including calcium signaling,
      bioenergetics, and apoptosis. Human cytomegalovirus is a medically important
      herpesvirus whose growth increases energy demand and depends upon continued cell
      survival. To gain insight into how human cytomegalovirus infection affects
      endoplasmic reticulum-mitochondrial contacts, we undertook quantitative
      proteomics of mitochondria-associated membranes using differential stable isotope
      labeling by amino acids in cell culture strategy and liquid chromatography-tandem
      MS analysis. This is the first reported quantitative proteomic analyses of a
      suborganelle during permissive human cytomegalovirus infection. Human fibroblasts
      were uninfected or human cytomegalovirus-infected for 72 h. Heavy mitochondria
      associated membranes were isolated from paired unlabeled, uninfected cells and
      stable isotope labeling by amino acids in cell culture-labeled, infected cells
      and analyzed by liquid chromatography-tandem MS analysis. The results were
      verified by a reverse labeling experiment. Human cytomegalovirus infection
      dramatically altered endoplasmic reticulum-mitochondrial contacts by late times.
      Notable is the increased abundance of several fundamental networks in the
      mitochondria-associated membrane fraction of human cytomegalovirus-infected
      fibroblasts. Chaperones, including HSP60 and BiP, which is required for human
      cytomegalovirus assembly, were prominently increased at endoplasmic reticulum
      mitochondrial contacts after infection. Minimal translational and translocation
      machineries were also associated with endoplasmic reticulum-mitochondrial
      contacts and increased after human cytomegalovirus infection as were glucose
      regulated protein 75 and the voltage dependent anion channel, which can form an
      endoplasmic reticulum-mitochondrial calcium signaling complex. Surprisingly,
      mitochondrial metabolic enzymes and cytosolic glycolytic enzymes were confidently
      detected in the mitochondria-associated membrane fraction and increased therein
      after infection. Finally, proapoptotic regulatory proteins, including Bax,
      cytochrome c, and Opa1, were augmented in endoplasmic reticulum-mitochondrial
      contacts after infection, suggesting attenuation of proapoptotic signaling by
      their increased presence therein. Together, these results suggest that human
      cytomegalovirus infection restructures the proteome of endoplasmic reticulum
      mitochondrial contacts to bolster protein translation at these junctions, calcium
      signaling to mitochondria, cell survival, and bioenergetics and, thereby, allow
      for enhanced progeny production.

PMID- 21742799
TI  - Modeling of pathological traits in Alzheimer's disease based on systemic
      extracellular signaling proteome.
AB  - The study of chronic brain diseases including Alzheimer's disease in patients is
      typically limited to brain imaging or psychometric testing. Given the epidemic
      rise and insufficient knowledge about pathological pathways in sporadic
      Alzheimer's disease, new tools are required to identify the molecular changes
      underlying this disease. We hypothesize that levels of specific secreted cellular
      signaling proteins in cerebrospinal fluid or plasma correlate with pathological
      changes in the Alzheimer's disease brain and can thus be used to discover
      signaling pathways altered in the disease. Here we measured 91 proteins of this
      subset of the cellular communication proteome in plasma or cerebrospinal fluid in
      patients with Alzheimer's disease and cognitively normal controls to
      mathematically model disease-specific molecular traits. We found small numbers of
      signaling proteins that were able to model key pathological markers of
      Alzheimer's disease, including levels of cerebrospinal fluid beta-amyloid and
      tau, and classify disease in independent samples. Several of these factors had
      previously been implicated in Alzheimer's disease supporting the validity of our
      approach. Our study also points to proteins which were previously unknown to be
      associated with Alzheimer's disease thereby implicating novel signaling pathways
      in this disorder.

PMID- 21742795
TI  - Myocardial AKT: the omnipresent nexus.
AB  - One of the greatest examples of integrated signal transduction is revealed by
      examination of effects mediated by AKT kinase in myocardial biology. Positioned
      at the intersection of multiple afferent and efferent signals, AKT exemplifies a
      molecular sensing node that coordinates dynamic responses of the cell in
      literally every aspect of biological responses. The balanced and nuanced nature
      of homeostatic signaling is particularly essential within the myocardial context,
      where regulation of survival, energy production, contractility, and response to
      pathological stress all flow through the nexus of AKT activation or repression.
      Equally important, the loss of regulated AKT activity is primarily the cause or
      consequence of pathological conditions leading to remodeling of the heart and
      eventual decompensation. This review presents an overview compendium of the
      complex world of myocardial AKT biology gleaned from more than a decade of
      research. Summarization of the widespread influence that AKT exerts upon
      myocardial responses leaves no doubt that the participation of AKT in molecular
      signaling will need to be reckoned with as a seemingly omnipresent regulator of
      myocardial molecular biological responses.

PMID- 21742800
TI  - Physiological adaptation of the bacterium Lactococcus lactis in response to the
      production of human CFTR.
AB  - Biochemical and biophysical characterization of CFTR (the cystic fibrosis
      transmembrane conductance regulator) is thwarted by difficulties to obtain
      sufficient quantities of correctly folded and functional protein. Here we have
      produced human CFTR in the prokaryotic expression host Lactococcus lactis. The
      full-length protein was detected in the membrane of the bacterium, but the yields
      were too low (< 0.1% of membrane proteins) for in vitro functional and structural
      characterization, and induction of the expression of CFTR resulted in growth
      arrest. We used isobaric tagging for relative and absolute quantitation based
      quantitative proteomics to find out why production of CFTR in L. lactis was
      problematic. Protein abundances in membrane and soluble fractions were monitored
      as a function of induction time, both in CFTR expression cells and in control
      cells that did not express CFTR. Eight hundred and forty six proteins were
      identified and quantified (35% of the predicted proteome), including 163 integral
      membrane proteins. Expression of CFTR resulted in an increase in abundance of
      stress-related proteins (e.g. heat-shock and cell envelope stress), indicating
      the presence of misfolded proteins in the membrane. In contrast to the reported
      consequences of membrane protein overexpression in Escherichia coli, there were
      no indications that the membrane protein insertion machinery (Sec) became
      overloaded upon CFTR production in L. lactis. Nutrients and ATP became limiting
      in the control cells as the culture entered the late exponential and stationary
      growth phases but this did not happen in the CFTR expressing cells, which had
      stopped growing upon induction. The different stress responses elicited in E.
      coli and L. lactis upon membrane protein production indicate that different
      strategies are needed to overcome low expression yields and toxicity.

PMID- 21742801
TI  - Principles of electrospray ionization.
AB  - Electrospray ionization is today the most widely used ionization technique in
      chemical and biochemical analysis. Interfaced with a mass spectrometer it allows
      the investigation of the molecular composition of liquid samples. With
      electrospray a large variety of chemical substances can be ionized. There is no
      limitation in mass which thus enables even the investigation of large noncovalent
      protein complexes. Its high ionization efficiency profoundly changed biomolecular
      sciences because proteins can be identified and quantified on trace amounts in a
      high throughput fashion. This review article focuses mainly on the exploration of
      the underlying ionization mechanism. Some ionization characteristics are
      discussed that are related to this mechanism. Typical spectra of peptides,
      proteins, and noncovalent complexes are shown and the quantitative character of
      spectra is highlighted. Finally the possibilities and limitations in measuring
      the association constant of bivalent noncovalent complexes are described.

PMID- 21742802
TI  - Fourier transform mass spectrometry.
AB  - This article provides an introduction to Fourier transform-based mass
      spectrometry. The key performance characteristics of Fourier transform-based mass
      spectrometry, mass accuracy and resolution, are presented in the view of how they
      impact the interpretation of measurements in proteomic applications. The theory
      and principles of operation of two types of mass analyzer, Fourier transform ion
      cyclotron resonance and Orbitrap, are described. Major benefits as well as
      limitations of Fourier transform-based mass spectrometry technology are discussed
      in the context of practical sample analysis, and illustrated with examples
      included as figures in this text and in the accompanying slide set. Comparisons
      highlighting the performance differences between the two mass analyzers are made
      where deemed useful in assisting the user with choosing the most appropriate
      technology for an application. Recent developments of these high-performing mass
      spectrometers are mentioned to provide a future outlook.

PMID- 21742803
TI  - The human proteome project: current state and future direction.
AB  - After the successful completion of the Human Genome Project, the Human Proteome
      Organization has recently officially launched a global Human Proteome Project
      (HPP), which is designed to map the entire human protein set. Given the lack of
      protein-level evidence for about 30% of the estimated 20,300 protein-coding
      genes, a systematic global effort will be necessary to achieve this goal with
      respect to protein abundance, distribution, subcellular localization, interaction
      with other biomolecules, and functions at specific time points. As a general
      experimental strategy, HPP research groups will use the three working pillars for
      HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge
      bases. The HPP participants will take advantage of the output and cross-analyses
      from the ongoing Human Proteome Organization initiatives and a chromosome-centric
      protein mapping strategy, termed C-HPP, with which many national teams are
      currently engaged. In addition, numerous biologically driven and disease-oriented
      projects will be stimulated and facilitated by the HPP. Timely planning with
      proper governance of HPP will deliver a protein parts list, reagents, and tools
      for protein studies and analyses, and a stronger basis for personalized medicine.
      The Human Proteome Organization urges each national research funding agency and
      the scientific community at large to identify their preferred pathways to
      participate in aspects of this highly promising project in a HPP consortium of
      funders and investigators.

PMID- 21742804
TI  - Attention interchanges at story-time: a case study from a deaf and hearing twin
      pair acquiring Swedish sign language in their deaf family.
AB  - This case study longitudinally analyzes and describes the changes of attentional
      expressions in interchanges between a pair of fraternal twins, 1 deaf and 1
      hearing, from the age of 10-40 months, and their Deaf family members. The video
      observed attentional expressions of initiating and reestablishing interchange
      were grouped in 5 functional categories: "getting," "directing," "maintaining,"
      "redirecting," and "checking" attention. Changes appear to be associated with
      development during the twins' ages of 10-13, 15-24, and 28-40 months, including
      the use of vision in communication. Although there are similarities in the
      changes of each twin's communicative initiations, there are also differences
      based on hearing status, personality, and use of modality. This is evident in the
      ways in which each twin's individual attention interchanges unfold over time; it
      is also connected with the parents' negotiating attention and arranging "seating
      positions" with them. Implications and findings for special educational purposes
      are discussed.

PMID- 21742805
TI  - Tumor engraftment in nude mice and enrichment in stroma- related gene pathways
      predict poor survival and resistance to gemcitabine in patients with pancreatic
      cancer.
AB  - PURPOSE: The goal of this study was to evaluate prospectively the engraftment
      rate, factors influencing engraftment, and predictability of clinical outcome of
      low-passage xenografts from patients with resectable pancreatic ductal
      adenocarcinoma (PDA) and to establish a bank of PDA xenografts. EXPERIMENTAL
      DESIGN: Patients with resectable PDA scheduled for resection at the Johns Hopkins
      Hospital were eligible. Representative pieces of tumor were implanted in nude
      mice. The status of the SMAD4 gene and content of tumor-generating cells were
      determined by immunohistochemistry. Gene expression was carried out by using a
      U133 Plus 2.0 array. Patients were followed for progression and survival.
      RESULTS: A total of 94 patients with PDA were resected, 69 tumors implanted in
      nude mice, and 42 (61%) engrafted. Engrafted carcinomas were more often SMAD4
      mutant, and had a metastatic gene expression signature and worse prognosis.
      Tumors from patients resistant to gemcitabine were enriched in stroma-related
      gene pathways. Tumors sensitive to gemcitabine were enriched in cell cycle and
      pyrimidine gene pathways. The time to progression for patients who received
      treatment with gemcitabine for metastatic disease (n = 7) was double in patients
      with xenografts sensitive to gemcitabine. CONCLUSION: A successful xenograft was
      generated in 61% of patients attempted, generating a pool of 42 PDA xenografts
      with significant biological information and annotated clinical data. Patients
      with PDA and SMAD4 inactivation have a better engraftment rate. Engraftment is a
      poor prognosis factor, and engrafted tumors have a metastatic gene expression
      signature. Tumors from gemcitabine-resistant patients were enriched in stromal
      pathways.

PMID- 21742806
TI  - Sequential FDG-PET/CT as a biomarker of response to Sunitinib in metastatic clear
      cell renal cancer.
AB  - PURPOSE: To test the hypothesis that sequential (18)F-fluorodeoxyglucose-positron
      emission tomography/computed tomography (FDG-PET/CT) is a correlative marker in
      metastatic clear cell renal cancer (mRCC), patients were treated with sunitinib.
      Three sequential scans were conducted to determine whether the timing of the
      investigation was relevant. EXPERIMENTAL DESIGN: Forty-four untreated mRCC
      patients were enrolled into this prospective phase II study. (18)F-FDG-PET/CT
      scans were conducted before (n = 44) and after 4 weeks (n = 43) and 16 weeks (n =
      40) of sunitinib given at standard doses. The primary endpoint was to correlate
      FDG-PET/CT response (20% reduction in SUV(max)) at 4 and 16 weeks with overall
      survival (OS). RESULTS: Forty-three (98%) patients had FDG-PET/CT avid lesions at
      diagnosis (median SUV(max) = 6.8, range: <2.5-18.4). In multivariate analysis, a
      high SUV(max) and an increased number of PET-positive lesions correlated with
      shorter OS [HR: 3.30 (95% CI: 1.36-8.45) and 3.67 (95% CI: 1.43-9.39),
      respectively]. After 4 weeks of sunitinib, a metabolic response occurred in 24
      (57%) patients, but this did not correlate with progression-free survival (HR for
      responders = 0.87; 95% CI: 0.40-1.99) or OS (HR for responders = 0.80; 95% CI:
      0.34-1.85). After 16 weeks of treatment, disease progression on FDG-PET/CT
      occurred in 28% (n = 12) patients which correlated with a decreased OS and PFS
      [HR = 5.96 (95% CI: 2.43-19.02) and HR = 12.13 (95% CI: 3.72-46.45),
      respectively]. CONCLUSIONS: Baseline FDG-PET/CT yields prognostic significant
      data. FDG-PET/CT responses occur in the majority of patients after 4 weeks of
      therapy; however, it is not until 16 weeks when the results become prognostically
      significant.

PMID- 21742807
TI  - Gene set enrichment analysis unveils the mechanism for the phosphodiesterase 4B
      control of glucocorticoid response in B-cell lymphoma.
AB  - PURPOSE: Resistance to glucocorticoid (GC) is a significant problem in the
      clinical management of lymphoid malignancies. Addressing this issue via a
      mechanistic understanding of relevant signaling pathways is more likely to yield
      positive outcomes. EXPERIMENTAL DESIGN: We used gene set enrichment analysis
      (GSEA), multiple genetic models of gain and loss of function in B-cell lymphoma
      cell lines, in vitro and in vivo, and primary patient samples to characterize a
      novel relationship between the cyclic AMP/phosphodiesterase 4B (cAMP/PDE4B),
      AKT/mTOR activities, and GC responses. RESULTS: Starting from the GSEA, we found
      that overexpression of the PDE4B in diffuse large B-cell lymphoma (DLBCL) impinge
      on the same genes/pathways that are abnormally active in GC-resistant tumors. We
      used genetically modified cell lines to show that PDE4B modulates cAMP inhibitory
      activities toward the AKT/mTOR pathway and defines GC resistance in DLBCL. In
      agreement with these data, pharmacologic inhibition of PDE4 in a xenograft model
      of human lymphoma unleashed cAMP effects, inhibited AKT, and restored GC
      sensitivity. Finally, we used primary DLBCL samples to confirm the clinical
      relevance and biomarker potential of AKT/mTOR regulation by PDE4B. CONCLUSIONS:
      Together, these data mechanistically elucidated how cAMP modulates GC responses
      in lymphocytes, defined AKT as the principal transducer of the growth inhibitory
      effects of cAMP in B cells, and allowed the formulation of genomics-guided
      clinical trials that test the ability of PDE4 inhibitors to restore GC
      sensitivity and improve the outcome of patients with B-cell malignancies.

PMID- 21742808
TI  - Robust gene expression signature from formalin-fixed paraffin-embedded samples
      predicts prognosis of non-small-cell lung cancer patients.
AB  - PURPOSE: The requirement of frozen tissues for microarray experiments limits the
      clinical usage of genome-wide expression profiling by using microarray
      technology. The goal of this study is to test the feasibility of developing lung
      cancer prognosis gene signatures by using genome-wide expression profiling of
      formalin-fixed paraffin-embedded (FFPE) samples, which are widely available and
      provide a valuable rich source for studying the association of molecular changes
      in cancer and associated clinical outcomes. EXPERIMENTAL DESIGN: We randomly
      selected 100 Non-Small-Cell lung cancer (NSCLC) FFPE samples with annotated
      clinical information from the UT-Lung SPORE Tissue Bank. We microdissected tumor
      area from FFPE specimens and used Affymetrix U133 plus 2.0 arrays to attain gene
      expression data. After strict quality control and analysis procedures, a
      supervised principal component analysis was used to develop a robust prognosis
      signature for NSCLC. Three independent published microarray datasets were used to
      validate the prognosis model. RESULTS: This study showed that the robust gene
      signature derived from genome-wide expression profiling of FFPE samples is
      strongly associated with lung cancer clinical outcomes and can be used to refine
      the prognosis for stage I lung cancer patients, and the prognostic signature is
      independent of clinical variables. This signature was validated in several
      independent studies and was refined to a 59-gene lung cancer prognosis signature.
      CONCLUSIONS: We conclude that genome-wide profiling of FFPE lung cancer samples
      can identify a set of genes whose expression level provides prognostic
      information across different platforms and studies, which will allow its
      application in clinical settings.

PMID- 21742809
TI  - Patterns of brain glucose metabolism induced by phosphodiesterase 10A inhibitors
      in the mouse: a potential translational biomarker.
AB  - Phosphodiesterase 10A (PDE10A) inhibitors have recently been proposed as a new
      therapy for schizophrenia. The aim of this study was to enhance our understanding
      of the role of PDE10A inhibitors and potentially identify a clinically useful
      mechanistic/functional biomarker by using 2-deoxyglucose (2-DG) autoradiography.
      PDE10A inhibitors papaverine (10 and 40 mg/kg), 6,7-dimethoxy-4-[(3R)-3-(2
      quinoxalinyloxy)-1-pyrrolidinyl]quinazoline (PQ-10), (0.16-10 mg/kg), and 2-[{4
      (1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy}methyl]quinoline (MP-10) (0.16
      40 mg/kg) induced region-specific hypermetabolism in the globus pallidus and
      lateral habenula of C57BL/6 mice. Studies with MP-10 revealed a dose-dependent
      relative increase in globus pallidus activation, whereas a bell-shaped curve was
      observed for the lateral habenula. Although the relative increase in 2-DG uptake
      in the lateral habenula was also characteristic of the D(2) antagonist
      haloperidol (0.01-0.63 mg/kg), relative 2-DG changes were absent in the globus
      pallidus. This observation probably is explained by the interaction of PDE10A
      inhibitors with the D(1) direct pathway as suggested by experiments in
      combination with the D(1) agonist (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl
      2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-82958) (0.16 mg/kg). The
      absence of an effect of MP-10 (2.5 mg/kg) on relative glucose metabolism in the
      globus pallidus and lateral habenula of PDE10A knockout mice confirmed the
      specificity of the signal induced by PDE10A inhibitors. These studies
      substantiate the regulatory role of PDE10A in the basal ganglia circuit and as
      such support the potential of PDE10A inhibitors for treating psychiatric
      disorders. Moreover, we could differentiate PDE10A inhibitors from haloperidol
      based on specific patterns of hypermetabolism probably caused by its combined
      action at both direct and indirect dopaminergic pathways. Finally, these specific
      changes in brain glucose metabolism may act as a translational biomarker for
      target engagement in future clinical studies.

PMID- 21742810
TI  - Herpes simplex virus type 2 seroprevalence and incidence in acute and chronic HIV
      1 infection.
AB  - Herpes simplex virus type 2 (HSV-2) HIV co-infection is common and associated
      with increased risk of HIV transmission. HSV-2 seroprevalence was assessed on
      stored samples from baseline and one year follow-up from 81 patients identified
      with acute HIV infection and 81 age-matched chronically infected men. HSV-2
      seroprevalence at baseline was lower for those with acute rather than chronic HIV
      infection, 51.9 versus 71.6% (P = 0.01); relative risk 0.72 (95% confidence
      interval [CI] 0.57-0.92). Since HSV-2 seroprevalence is lower in those newly HIV
      infected, the diagnosis of early HIV infection may allow for counselling to
      reduce subsequent HSV-2 acquisition.

PMID- 21742811
TI  - Reticence to prescribe: utilization of expedited partner therapy among obstetrics
      providers in Arizona.
AB  - Expedited partner therapy (EPT) is the practice of providing an extra dose or
      prescription of antibiotic to patients diagnosed with chlamydia or gonorrhoea to
      deliver to their sexual partner(s). Obstetrical providers who delivered more than
      20 infants in Maricopa County, Arizona, USA, during the year 2008 were surveyed
      by telephone regarding their use of EPT. A total of 142 eligible respondents
      completed the survey, representing 34% (142/421) of the delivering providers, 67
      (47%) of whom reported the use of EPT in their clinics. Having received
      information about EPT was significantly associated with its use (67% versus 41%)
      (P = 0.008). The most common reasons for not using EPT included the inability to
      obtain allergy history in partners (24%) and concern for liability (11%).
      Additional education regarding the use of EPT may increase the use of this
      personal and public health tool among some obstetrics providers in Maricopa
      County; however, concerns for liability may limit broad utilization.

PMID- 21742812
TI  - Is azithromycin adequate treatment for asymptomatic rectal chlamydia?
AB  - Rectal chlamydia is a common sexually transmissible infection (STI) in men who
      have sex with men (MSM) that is predominantly asymptomatic. The recommended
      treatment of azithromycin 1 g as a single oral dose has not been subject to
      randomized trials and so its efficacy is unknown. We conducted a retrospective
      case-note review of all MSM diagnosed at the Sydney Sexual Health Centre with
      asymptomatic rectal chlamydia in 2009. We identified 116 MSM who received
      azithromycin; 85 (73%) attended for the recommended re-test at varying times
      (median 78 days, range 21-372 days). Of the men who returned, 11 (13%) had a
      persistently positive result; we reviewed behavioural data to classify these men
      as probable re-infections (6/11) or possible treatment failures (5/11),
      suggesting an efficacy of 94%. Until a randomized controlled trial (RCT) is
      conducted, patients with rectal chlamydia should be encouraged to attend for a re
      test at 6-12 weeks.

PMID- 21742813
TI  - USA study of sex toy use by HIV-positive men who have sex with other men:
      implications for sexual health.
AB  - HIV/AIDS disproportionately impacts men who have sex with men (MSM) in the USA.
      Most existing literature on MSM with HIV focuses on transmission risk, but does
      not acknowledge health-promoting sexual behaviours men may undertake. This study
      examined sex toy use within this population to describe the extent to which using
      toys is incorporated into their sexual repertoires as a risk reduction practice.
      Data regarding sociodemographics, sexual/health-related behaviours and sex toy
      use were collected from 2275 MSM using an online survey. Most participants
      reported being sexually active (88.5%), and the majority (70.2%) of participants
      reported sex toy use within the previous year. Sex toy users were more likely to
      be white, in sexual relationships with others, and reported higher levels of
      sexual satisfaction. Given that sex toy use is common among this population, room
      for discussion exists about sex toys as tools to enhance pleasure and reduce
      HIV/sexually transmitted infection (STI) transmission.

PMID- 21742814
TI  - The ROOT DETERMINED NODULATION1 gene regulates nodule number in roots of Medicago
      truncatula and defines a highly conserved, uncharacterized plant gene family.
AB  - The formation of nitrogen-fixing nodules in legumes is tightly controlled by a
      long-distance signaling system in which nodulating roots signal to shoot tissues
      to suppress further nodulation. A screen for supernodulating Medicago truncatula
      mutants defective in this regulatory behavior yielded loss-of-function alleles of
      a gene designated ROOT DETERMINED NODULATION1 (RDN1). Grafting experiments
      demonstrated that RDN1 regulatory function occurs in the roots, not the shoots,
      and is essential for normal nodule number regulation. The RDN1 gene,
      Medtr5g089520, was identified by genetic mapping, transcript profiling, and
      phenotypic rescue by expression of the wild-type gene in rdn1 mutants. A mutation
      in a putative RDN1 ortholog was also identified in the supernodulating nod3
      mutant of pea (Pisum sativum). RDN1 is predicted to encode a 357-amino acid
      protein of unknown function. The RDN1 promoter drives expression in the vascular
      cylinder, suggesting RDN1 may be involved in initiating, responding to, or
      transporting vascular signals. RDN1 is a member of a small, uncharacterized,
      highly conserved gene family unique to green plants, including algae, that we
      have named the RDN family.

PMID- 21742815
TI  - Reversible pulmonary toxicity due to lenalidomide.
AB  - Lenalidomide is a derivative of thalidomide and is FDA-approved for the treatment
      of myelodysplastic syndrome and, in combination with dexamethasone, for the
      treatment of relapsed multiple myeloma. Pulmonary toxicity with thalidomide is a
      recognized potential complication; however, there have only been two case reports
      in the literature of lenalidomide-associated pulmonary toxicity. In this case, we
      describe a patient who developed profound dyspnea, decreased exercisetolerance,
      and new ground-glass opacities with reticulation, consistent with a nonspecific
      interstitial pneumonia pattern. Clinical suspicion for pulmonary drug toxicity
      was high and lenalidomide was discontinued. Within 2 weeks of stopping
      lenalidomide, the patient had significant improvement in dyspnea and interstitial
      changes on CT were resolving. After 8 weeks, there was complete resolution of
      symptoms. Lenalidomide-induced pulmonary toxicity is significantly debilitating
      but, to date, it appears to be reversible with discontinuation of the medication.

PMID- 21742816
TI  - Sphingomonas polyaromaticivorans sp. nov., a polycyclic aromatic hydrocarbon
      degrading bacterium from an oil port water sample.
AB  - A bacterial strain (B2-7(T)) capable of degrading a wide range of polycyclic
      aromatic hydrocarbon compounds (2-4 rings) was isolated from a water sample taken
      from Botan Oil Port in Xiamen, China. The isolate was Gram-negative, short-rod
      shaped, aerobic, non-motile and formed yellow-pigmented colonies on LB medium.
      Cells of strain B2-7(T) were catalase-positive and oxidase-negative. Optimal
      growth of strain B2-7(T) was observed at pH 7.0, at 26  degrees C and in 0.5 %
      NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that
      strain B2-7(T) grouped with members of the genus Sphingomonas and it showed 16S
      rRNA gene sequence similarity of 95.40 % to Sphingomonas yunnanensis YIM 003(T).
      The major polar lipids were phosphatidylethanolamine, phosphatidylcholine and
      sphingoglycolipid. Q-10 and sym-homospermidine were the predominant ubiquinone
      and polyamine components, respectively. The major fatty acids were C(18:1)omega7c
      (67.2 %), C(14:0) 2-OH (10.0 %) and C(16:0) (9.6 %). The G+C content of the
      genomic DNA was 61.8 mol%. Based on phenotypic properties, and phylogenetic and
      genomic data, strain B2-7(T) represents a novel species of the genus Sphingomonas
      within the class Alphaproteobacteria, for which the name Sphingomonas
      polyaromaticivorans sp. nov. is proposed. The type strain is B2-7(T) ( = KCCM
      42951(T) = JCM 16711(T)).

PMID- 21742817
TI  - Nocardia goodfellowii sp. nov. and Nocardia thraciensis sp. nov., isolated from
      soil.
AB  - The taxonomic position of two soil actinomycetes, strains A2012(T) and A2019(T),
      isolated from Turkish soils, was determined using a polyphasic approach.
      Comparative 16S rRNA gene sequence analysis showed that the strains belonged to
      the family Nocardiaceae. Strains A2012(T) and A2019(T) were most closely related
      to Nocardia caishijiensis DSM 44831(T) (98.9 %) and Nocardia mexicana CIP
      108295(T) (98.6 %), respectively; similarity to other type strains of the genus
      Nocardia ranged from 96.9 to 97.9 %. However, DNA-DNA relatedness and phenotypic
      data demonstrated that strains A2012(T) and A2019(T) could be clearly
      distinguished from members of the most closely related Nocardia species. It is
      evident from the genotypic and phenotypic data that the two isolates represent
      two novel species of the genus Nocardia. It is proposed, therefore, that strains
      A2012(T) and A2019(T) be classified in the genus Nocardia as representatives of
      Nocardia goodfellowii sp. nov. (type strain A2012(T) = DSM 45516(T) = NRRL B
      24833(T) = KCTC 19986(T)) and Nocardia thraciensis sp. nov. (type strain A2019(T)
      = DSM 45517(T) = NRRL B-24834(T) = KCTC 19985(T)), respectively.

PMID- 21742818
TI  - Mycobacterium litorale sp. nov., a rapidly growing mycobacterium from soil.
AB  - A gram-positive, acid-fast and rapidly growing rod, designated F4(T), was
      isolated from a soil sample of Haikou in China. The isolate shared 98.2 % 16S
      rRNA gene sequence similarity with Mycobacterium monacense B9-21-178(T), 96.2 %
      hsp65 sequence similarity with M. monacense FI-05352 and 79.6 % 16S-23S rRNA
      internal transcribed spacer sequence similarity with M. monacense B9-21-178(T).
      DNA-DNA relatedness between the isolate and M. monacense DSM 44395(T) was 43.5 %.
      The morphological analysis and physiological tests also showed that the isolate
      differed from any strain reported to date. The mycolic acid profile and the
      cellular fatty acid composition were also determined. On the basis of phenotypic
      and chemotaxonomic characteristics and phylogenetic data, it was concluded that
      strain F4(T) ( = CGMCC 4.5724(T) = JCM 17423(T)) merited classification as the
      type strain of a novel species, for which the name Mycobacterium litorale sp.
      nov. is proposed.

PMID- 21742819
TI  - Nocardioides daejeonensis sp. nov., a denitrifying bacterium isolated from sludge
      in a sewage-disposal plant.
AB  - Strain MJ31(T), a gram-reaction-positive, aerobic, rod-shaped, non-motile
      bacterium, was isolated from a sludge sample collected at the Daejeon sewage
      disposal plant, in South Korea, and characterized in order to determine its
      taxonomic position. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain MJ31(T) belonged to the genus Nocardioides, appearing most
      closely related to Nocardioides dubius KSL-104(T) (98.6 % sequence similarity),
      Nocardioides jensenii DSM 20641(T) (97.6 %), Nocardioides daedukensis MDN22(T)
      (97.2 %) and Nocardioides mesophilus MSL-22(T) (97.0 %). The chemotaxonomic
      properties of strain MJ31(T) were consistent with those of the genus
      Nocardioides: MK-8(H(4)) was the predominant menaquinone, iso-C(16 : 0), iso-C(17
      : 0) and C(18 : 1)omega9c were the predominant cellular fatty acids, and the cell
      wall peptidoglycan was based on LL-2,6-diaminopimelic acid. The genomic DNA G+C
      content of strain MJ31(T) was 71.2 mol%. Some differential phenotypic properties
      and low DNA-DNA relatedness values (<28 %) with the type strains of closely
      related species indicated that strain MJ31(T) represents a novel species, for
      which the name Nocardioides daejeonensis sp. nov. is proposed. The type strain is
      MJ31(T) ( = KCTC 19772(T) = JCM 16922(T)).

PMID- 21742820
TI  - Azospirillum formosense sp. nov., a diazotroph from agricultural soil.
AB  - A gram-negative, spiral or rod-shaped, non-spore-forming diazotrophic bacterium,
      designated CC-Nfb-7(T), was isolated from agricultural soil in Yunlin County,
      Taiwan. 16S rRNA gene sequence analysis showed that strain CC-Nfb-7(T) was most
      closely related to Azospirillum brasilense DSM 1690(T) (97.4 % 16S rRNA gene
      sequence similarity), Azospirillum rugosum IMMIB AFH-6(T) (96.8 %) and
      Azospirillum oryzae JCM 21588(T) (96.6 %); <96.5 % 16S rRNA gene sequence
      similarity was found with all other members of the genus Azospirillum. DNA-DNA
      relatedness between strain CC-Nfb-7(T) and A. brasilense DSM 1690(T), A. rugosum
      DSM 19657(T) and A. oryzae JCM 21588(T) was 38.9, 30.1 and 31.8 %, respectively.
      The respiratory quinone was ubiquinone Q-10. The major fatty acids were summed
      feature 8 (consisting of C(18 : 1)omega7c and/or C(18 : 1)omega6c), summed
      feature 3 (consisting of C(16 : 1)omega7c and/or C(16 : 1)omega6c), summed
      feature 2 (consisting of C(14 : 0) 3-OH and/or iso-C(16 : 1) I), C(16 : 0), C(18
      : 0) 2-OH and C(16 : 0) 3-OH. The polar lipids consisted mainly of
      phosphatidylglycerol, phosphatidylcholine and one unidentified phospholipid.
      Furthermore, moderate amounts of phosphatidylethanolamine,
      phosphatidyldimethylethanolamine and one unidentified aminophospholipid were also
      detected. Strain CC-Nfb-7(T) could be distinguished from members of
      phylogenetically related species by differences in phenotypic properties. On the
      basis of morphological, chemotaxonomic and phylogenetic data, strain CC-Nfb-7(T)
      represents a novel species within the genus Azospirillum, for which we propose
      the name Azospirillum formosense sp. nov. The type strain is CC-Nfb-7(T) ( = BCRC
      80273(T) = JCM 17639(T) = DSM 24137(T)).

PMID- 21742821
TI  - Sandaracinus amylolyticus gen. nov., sp. nov., a starch-degrading soil
      myxobacterium, and description of Sandaracinaceae fam. nov.
AB  - A novel starch-degrading myxobacterium designated NOSO-4(T) (new organism of the
      Sorangiineae strain 4) was isolated in 1995 from a soil sample containing plant
      residues, collected in Lucknow, Uttar Pradesh, India. The novel bacterium shows
      typical myxobacterial characteristics such as gram-negative, rod-shaped
      vegetative cells, swarming colonies, fruiting body-like aggregates and
      bacteriolytic activity. The strain is mesophilic, strictly aerobic and
      chemoheterotrophic. Based on 16S rRNA gene sequences, NOSO-4(T) shows highest
      similarity (96.2 %) with the unidentified bacterial strain O29 (accession no.
      FN554397), isolated from leek (Allium porrum) rhizosphere, and to the
      myxobacteria Jahnella thaxteri (88.9 %) and Chondromyces pediculatus (88.5 %).
      Major fatty acids are C(17 : 1) 2-OH, C(20 : 4)omega6 (arachidonic acid), and the
      straight-chain fatty acids C(17 : 0), C(15 : 0) and C(16 : 0). The genomic DNA
      G+C content of the novel isolate is 66.8 mol%. It is proposed that strain NOSO
      4(T) represents a novel species in a new genus, i.e. Sandaracinus amylolyticus
      gen. nov., sp. nov., but also belongs to a new family, Sandaracinaceae fam. nov.
      The type strain of the type species, S. amylolyticus sp. nov., is NOSO-4(T) ( =
      DSM 53668(T) = NCCB 100362(T)).

PMID- 21742822
TI  - Reclassification of Rhizobium tropici type A strains as Rhizobium leucaenae sp.
      nov.
AB  - Rhizobium tropici is a well-studied legume symbiont characterized by high genetic
      stability of the symbiotic plasmid and tolerance to tropical environmental
      stresses such as high temperature and low soil pH. However, high phenetic and
      genetic variabilities among R. tropici strains have been largely reported, with
      two subgroups, designated type A and B, already defined within the species. A
      polyphasic study comprising multilocus sequence analysis, phenotypic and
      genotypic characterizations, including DNA-DNA hybridization, strongly supported
      the reclassification of R. tropici type A strains as a novel species. Type A
      strains formed a well-differentiated clade that grouped with R. tropici,
      Rhizobium multihospitium, Rhizobium miluonense, Rhizobium lusitanum and Rhizobium
      rhizogenes in the phylogenies of the 16S rRNA, recA, gltA, rpoA, glnII and rpoB
      genes. Several phenotypic traits differentiated type A strains from all related
      taxa. The novel species, for which the name Rhizobium leucaenae sp. nov. is
      proposed, is a broad host range rhizobium being able to establish effective root
      nodule symbioses with Leucaena leucocephala, Leucaena esculenta, common beans
      (Phaseolus vulgaris) and Gliricidia sepium. Strain CFN 299(T) ( = USDA 9039(T) =
      LMG 9517(T) = CECT 4844(T) = JCM 21088(T) = IAM 14230(T) = SEMIA 4083(T) = CENA
      183(T) = UMR1026(T) = CNPSo 141(T)) is designated the type strain of Rhizobium
      leucaenae sp. nov.

PMID- 21742827
TI  - Vancomycin minimum inhibitory concentration and outcome in patients with
      Staphylococcus aureus bacteremia: pearl or pellet?

PMID- 21742828
TI  - Adjuvant anti-tumor necrosis factor therapy for staphylococcal arthritis and
      sepsis: a cautionary note.

PMID- 21742829
TI  - Population effectiveness, not efficacy, should decide who gets vaccinated against
      human papillomavirus via publicly funded programs.

PMID- 21742830
TI  - Refugees, mass casualties, and hepatitis B transmission.

PMID- 21742831
TI  - Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus
      aureus bacteremia and high vancomycin minimum inhibitory concentrations.
AB  - BACKGROUND: There are concerns about reduced efficacy of vancomycin in patients
      with Staphylococcus aureus bacteremia (SAB), especially when the minimum
      inhibitory concentration (MIC) nears the upper limit of the susceptible range.
      METHODS: We examined the relationship between antibiotic treatment, 30-day
      mortality, and microbiologic parameters in a large Australasian cohort of
      patients with SAB. RESULTS: We assessed 532 patients with SAB from 8 hospitals.
      All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated
      with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA)
      bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin
      MIC was associated with increased mortality in vancomycin-treated patients.
      However, even in patients with MSSA bacteremia treated with flucloxacillin,
      mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5
      MUg/mL, compared with those with lower MIC isolates (26.8% vs 12.2%; P < .001).
      After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin
      MIC were independently associated with mortality, but methicillin resistance and
      antibiotic choice were not. CONCLUSIONS: We have confirmed an association between
      higher vancomycin MIC and increased mortality in patients with SAB, but
      surprisingly this relationship was not related to the antibiotic treatment
      received, suggesting that the use of vancomycin per se is not responsible for the
      poorer outcome.

PMID- 21742832
TI  - The combination of a tumor necrosis factor inhibitor and antibiotic alleviates
      staphylococcal arthritis and sepsis in mice.
AB  - BACKGROUND: Despite advances in medical practices, in recent decades permanent
      reductions in joint function have not been achieved, and the high mortality rate
      of patients with staphylococcal septic arthritis has not substantially improved.
      METHODS: We evaluated the effects of a combined tumor necrosis factor (TNF)
      inhibitor and antibiotic therapy on the course of Staphylococcus aureus arthritis
      and sepsis in mice. RESULTS: Treatment with the combination of a TNF inhibitor
      and an antibiotic resulted in a quicker relief of clinical arthritis in mice with
      septic arthritis, compared with an antibiotic monotherapy. Both
      histopathologically verified synovitis and the extent of joint destruction were
      reduced by this combined treatment. Importantly, anti-TNF treatment significantly
      improved the survival rate of mice with S. aureus sepsis and staphylococcal
      enterotoxin shock syndrome; this effect might be the result of a partial
      restoration of the hemostatic balance between coagulation and fibrinolysis.
      Finally, we demonstrated that anti-TNF treatment downregulates high-mobility
      group protein B1 in staphylococcal enterotoxin shock syndrome. CONCLUSIONS: Thus,
      simultaneous systemic TNF inhibition and antibiotic therapy has beneficial
      effects on the outcome of S. aureus arthritis and sepsis in a mouse model,
      suggesting that the combination of a TNF inhibitor and antibiotics represents a
      novel therapeutic strategy for the treatment of staphylococcal infections.

PMID- 21742833
TI  - Early deaths during tuberculosis treatment are associated with depressed innate
      responses, bacterial infection, and tuberculosis progression.
AB  - Up to 14% of Malawian adults die during the intensive phase of tuberculosis
      treatment. In a prospective cohort of 199 Malawian adults with microbiologically
      confirmed pulmonary tuberculosis, clinical and laboratory parameters were
      compared between those who died or deteriorated with those who had an uneventful
      recovery. Baseline tumor necrosis factor alpha responses to stimulation with heat
      killed Mycobacterium tuberculosis and lipopolysaccharide were reduced among the
      22 patients with poor outcome (P = .017). Low body mass index (P = .002) and
      elevated respiratory rate (P = .01) at tuberculosis diagnosis independently
      predicted poor outcome. Validation of a clinical score identifying high-risk
      individuals is warranted, together with further investigation of immunological
      derangements.

PMID- 21742834
TI  - Bacteroides fragilis-stimulated interleukin-10 contains expanding disease.
AB  - Commensal symbionts may become pathogens upon escaping their habitat. In the gut,
      Bacteroides fragilis protects against colitis through induction of interleukin 10
      (IL-10) by CD4(+) T cells. When intestinal integrity is disrupted, B. fragilis
      and colonic contents escape into the peritoneum, causing abscesses and
      bacteremia. Whether the virulence mechanisms employed by B. fragilis during
      infections differ from those employed for symbiosis during commensalism is
      unknown. We demonstrate T cell-independent IL-10 production in response to B.
      fragilis during its pathogenic interactions with the host, and demonstrate the
      ability of the whole organism to activate Toll-like receptor 2-mediated MyD88
      signaling in macrophages. Upon challenge with B. fragilis, mortality rates and
      serum proinflammatory cytokine levels were higher among IL-10(-/-) mice than
      among wild-type mice. Deaths were due to exuberant proinflammatory responses, not
      increased bacterial burden. During infection or commensalism, induction of IL-10
      by B. fragilis is critical to this microbe's interactions with the immune system.

PMID- 21742835
TI  - Incremental impact of adding boys to current human papillomavirus vaccination
      programs: role of herd immunity.
AB  - Our aim was to examine the potential incremental impact of vaccinating boys
      against human papillomavirus (HPV) on vaccine-type infection in females and
      males, using an individual-based HPV transmission-dynamic model. Under base
      assumptions (vaccine efficacy = 99%, duration of protection = 20 years, coverage
      = 70%), vaccinating 12-year-old boys, in addition to girls, resulted in an
      incremental reduction in HPV-16/18 (HPV-6/11) incidence over 70 years of 16% (3%)
      in females and 23% (4%) in males. The benefit of vaccinating boys decreased with
      improved vaccination coverage in girls. Given the important predicted herd
      immunity impact of vaccinating girls under moderate to high vaccine coverage, the
      potential incremental gains of vaccinating boys are limited.

PMID- 21742836
TI  - Until which age should women be vaccinated against HPV infection? Recommendation
      based on cost-effectiveness analyses.
AB  - INTRODUCTION: Cervical cancer is caused by infection with human papillomavirus
      (HPV). Several countries have implemented vaccination programs against HPV for
      teenage girls before sexual debut. However, recent clinical trials have
      demonstrated that vaccination of older women is highly effective as well.
      Accordingly, it has been suggested that these older women should also be offered
      vaccination. Here, the cost-effectiveness of HPV vaccination for older women was
      assessed. METHODS: A Markov model was used to estimate age-specific health
      benefits and cost savings of HPV vaccination for women 12-50 years of age, in the
      Netherlands. Sensitivity analyses were performed to test the robustness of the
      outcomes. State-of-the-art health-economic methods were used, and international
      health-economic guidelines were followed. RESULTS: HPV vaccination is highly cost
      effective for girls aged 12-16 years. Remarkably, cost-effectiveness only slowly
      declines with increasing age of the vaccinees up to 25 years. Indeed, substantial
      health benefits can be obtained by vaccinating women in this age group at
      acceptable costs. Beyond this age, cost-effectiveness of HPV-vaccination rapidly
      declines. CONCLUSIONS: Not only HPV vaccination of girls before sexual debut is a
      highly effective and cost-effective strategy for prevention of cervical cancer,
      but also vaccination of women until the age of 25 years is generally cost
      effective.

PMID- 21742837
TI  - Clustering of multiple human papillomavirus infections in women from a population
      based study in Guanacaste, Costa Rica.
AB  - OBJECTIVE: To evaluate clustering patterns of prevalent infection with multiple
      human papillomavirus (HPV) types in 8365 nonhysterectomized women from the
      Guanacaste Study of HPV Natural History. METHODS: HPV testing was performed on
      cervical cells by MY09/M11 L1 degenerate consensus primer polymerase chain
      reaction method, with dot-blot hybridization for genotyping. Logistic regression
      was used to model type-specific HPV positivity, adjusted for age, lifetime number
      of sexual partners, and specific HPV type prevalence. Woman-level random effects
      were added to represent unobservable risk factors common to all HPV types.
      RESULTS: The observed-to-expected ratio for infections with 2 types was 1.16 (95%
      credible interval: 1.11-1.21) and for >=3 types was 1.04 (95% credible interval:
      .96-1.13). The tendency of HPV types to cluster increased significantly with the
      genetic similarity of L1 regions. P value < .01 was observed for 2 HPV pairs: HPV
      62 and -81 were found together more, while HPV-51 and -71 were found together
      less often than expected. CONCLUSIONS: We found a small degree of aggregation
      between any HPV types and lack of clustering between specific carcinogenic types.
      Our data indirectly provide reassurance on lack of misclassification for the
      large majority of HPV types in multiple infections detected by the MY09/11 method
      and genotyped using dot-blot hybridization.

PMID- 21742838
TI  - Hepatitis B outbreak following a mass-casualty incident, Australia.
AB  - On 16 April 2009, a boat carrying 47 Afghan asylum seekers and 2 Indonesian crew
      exploded in Australian waters, resulting in mass casualties. Of these casualties,
      23 persons who suffered significant burns were transferred to Royal Perth
      Hospital, Perth, Western Australia. One patient was subsequently shown to be a
      hepatitis B virus (HBV) carrier at the time of the explosion. Over the following
      months, 3 other patients received a diagnosis of acute hepatitis B, and an
      additional 4 patients showed serological evidence of recent HBV infection,
      including 1 patient who was transferred to another Australian city. Molecular
      typing determined that the strains from the HBV carrier and the acute and recent
      case patients formed a closely related cluster, and the investigation suggested
      that transmission occurred at or around the time of the boat explosion. This is
      the first report of confirmed transmission of HBV following a disaster, and it
      reinforces the importance of postexposure prophylaxis for HBV in mass casualty
      situations.

PMID- 21742839
TI  - Viral determinants of hepatitis B surface antigen seroclearance in hepatitis B e
      antigen-negative chronic hepatitis B patients.
AB  - BACKGROUND: We studied whether quantification of serum HBsAg and HBV DNA levels
      could predict spontaneous HBsAg clearance in patients with negative hepatitis B e
      antigen (HBeAg). METHODS: Serum HBsAg and HBV DNA levels were measured at
      baseline among a longitudinal cohort of 103 HBeAg-negative patients recruited
      since 1997. RESULTS: Twelve (12%) patients developed HBsAg seroclearance after 88
      +/- 26 months (range, 21-139) of follow-up. At baseline, the serum HBsAg level
      among patients who cleared HBsAg (1.30 +/- 1.27 log IU/mL) was significantly
      lower than those who did not clear HBsAg (2.96 +/- 0.84 log IU/mL; P < .001). The
      area under receiver operating characteristics (ROC) curve for serum HBsAg to
      predict HBsAg seroclearance was 0.90 (95% confidence interval [CI], 0.83-0.97; P
      < .001). Nine (75%) of 12 patients who had HBsAg seroclearance versus 8 (9%) of
      91 who remained HBsAg-positive had serum HBsAg <=100 IU/mL at the baseline (P <
      .001). An HBsAg cutoff of <=100 IU/mL had 75% sensitivity and 91% specificity to
      predict HBsAg seroclearance. Baseline serum HBV DNA could not predict HBsAg
      seroclearance; the area under ROC curve was 0.64 (95% CI, 0.46-0.81; P = .13).
      CONCLUSIONS: Single-point serum HBsAg level can predict the chance of HBsAg
      seroclearance in chronic hepatitis B patients with negative HBeAg.

PMID- 21742840
TI  - Serum HBsAg decline during long-term potent nucleos(t)ide analogue therapy for
      chronic hepatitis B and prediction of HBsAg loss.
AB  - Nucleos(t)ide analogues strongly inhibit viral replication in chronic hepatitis B
      (CHB) infection, but knowledge of their long-term effect on serum hepatitis B
      surface antigen (HBsAg) levels and HBsAg loss is lacking. Seventy-five CHB
      patients with virological response (VR) to ETV or TDF were included. HBsAg
      decline 2 years after VR was most pronounced in HBeAg-positive patients. Age,
      alanine aminotransferase, and HBeAg loss were associated with HBsAg decline in
      HBeAg-positive patients. Predicted median time to HBsAg loss was 36 years for
      HBeAg-positive and 39 years for HBeAg-negative patients. Thus, most patients
      treated with ETV and TDF will probably need decades of therapy to achieve HBsAg
      loss.

PMID- 21742841
TI  - IL28B genotype effects during early treatment with peginterferon and ribavirin in
      difficult-to-treat hepatitis C virus infection.
AB  - BACKGROUND: Mathematical models of hepatitis C virus (HCV) during therapy may
      elucidate mechanisms of action for antiviral therapy. In genome-wide association
      studies, IL28B gene polymorphisms are highly predictive of therapeutic clearance
      of HCV. METHODS: We collected sera from 20 chronically infected HCV participants
      at 13 points during the first 28 days of therapy. We assessed the presence of the
      C allele at single-nucleotide polymorphism rs12979860 using the ABI TaqMan
      allelic discrimination kit. We estimated dynamic parameters from the entire
      population using the Neumann model for HCV infection. Statistical methods for
      repeated nonlinear measures compared model parameters by established predictors
      of response. RESULTS: The frequencies of IL28B genotypes were 6 (C/C), 11 (C/T),
      and 3 (T/T). The mean log decline in HCV RNA from 0 to 48 hours was more rapid
      among C/C genotype participants compared with C/T or T/T genotype participants
      (1.4 vs 0.7; P = .07), and from 2 days to 14 days (1.6 vs 0.7; P = .04). In the
      multivariate model, the C/C genotype predicted a steeper second-phase decline
      when adjusted for race (P = .01). CONCLUSIONS: The presence of the C/C genotype
      at IL28B rs12979860 exerts its antiviral effect by increasing the infected
      hepatocyte death rate. This suggests that an immune-mediated mechanism is
      responsible.

PMID- 21742842
TI  - Increasing the time of exposure to aerosol measles vaccine elicits an immune
      response equivalent to that seen in 9-month-old Mexican children given the same
      dose subcutaneously.
AB  - BACKGROUND: A 30-second aerosol measles vaccination successfully primes children
      12 months of age and older but is poorly immunogenic when given to 9-month-old
      children. We examined the immune responses when increasing the duration to
      aerosol exposure in 9-month-olds. METHODS: One hundred and thirteen healthy 9
      month-old children from Mexico City were enrolled; 58 received aerosol EZ measles
      vaccine for 2.5 minutes and 55 subcutaneously. Measles-specific neutralizing
      antibodies and cellular responses were measured before and at 3 and 6 months
      postimmunization. RESULTS: Adaptive immunity was induced in 97% after aerosol and
      98% after subcutaneous administration. Seroconversion rates and GMCs were 95% and
      373 mIU/mL (95% confidence interval [CI], 441-843) following aerosol vaccination
      and 91% and 306 mIU/mL (95% CI, 367-597) after subcutaneous administration at 3
      months. The percentage of children with a measles-specific stimulation index >=3
      was 45% and 60% in the aerosol versus 55% and 59% in the subcutaneous group at 3
      and 6 months, respectively. CD8 memory cell frequencies were higher in the
      aerosol group at 3 months compared with the subcutaneous group. Adverse reactions
      were comparable in both groups. CONCLUSIONS: Increasing exposure time to aerosol
      measles vaccine elicits immune responses that are comparable to those seen when
      an equivalent dose is administered by the subcutaneous route in 9-month-old
      infants.

PMID- 21742843
TI  - Common SNPs/haplotypes in IL18R1 and IL18 genes are associated with variations in
      humoral immunity to smallpox vaccination in Caucasians and African Americans.
AB  - BACKGROUND: Identifying genetic factors that influence poxvirus immunity across
      races may assist in the development of better vaccines and approaches for vaccine
      development. METHODS: We performed an extensive candidate-gene genetic screen
      (across 32 cytokine and cytokine receptor genes) in a racially diverse cohort of
      1056 healthy adults after a single dose of smallpox vaccine. Associations between
      single-nucleotide polymorphisms (SNPs)/haplotypes and vaccinia virus-specific
      neutralizing antibodies were assessed using linear regression methodologies.
      RESULTS: The combined analysis identified 63 associations between candidate SNPs
      and antibody levels after smallpox vaccination with P < .05. Thirty-one of these
      were within the IL18R1 and IL18 genes. Five IL18R1 SNPs, including a coding
      synonymous polymorphism rs1035130 (Phe251Phe) and 2 promoter SNPs (rs6710885,
      rs2287037), all in linkage disequilibrium, were associated with significant
      variations in antibody levels in both Caucasians (P <= .016) and African
      Americans (P <= .025). Similarly, associations with 2 intronic IL18 SNPs
      (rs2043055 and rs5744280) were consistent in the Caucasian (P <= .023) and
      African American samples (P <= .014). Haplotype analysis revealed highly
      significant associations between IL18R1 haplotypes and vaccinia virus-specific
      antibody levels (P < .001, by combined analysis) that were consistent across
      races. CONCLUSIONS: Our study provides evidence for IL18 and IL18R1 genes as
      plausible genes regulating the humoral immune response to smallpox vaccine in
      both Caucasians and African Americans.

PMID- 21742844
TI  - Interference and facilitation between dengue serotypes in a tetravalent live
      dengue virus vaccine candidate.
AB  - BACKGROUND: Live, multivalent vaccines have historically exhibited interference
      in humans; live dengue virus (DENV) vaccines have proven no exception. METHODS:
      To characterize interactions between DENV serotypes in a tetravalent live
      attenuated virus vaccine candidate, we analyzed data from a factorial clinical
      trial in which all combinations of high- and low-dose DENV serotypes were
      combined in 16 live-attenuated tetravalent vaccine formulations (N = 64) and
      administered to flavivirus-naive adult volunteers. Regression models considered
      the outcomes of reactogenicity and seroconversion, controlling for all serotype
      doses simultaneously. Additionally, results were compared against earlier
      evaluations of the same viruses administered as monovalent formulations. RESULTS:
      DENV-1 was immunologically dominant in both monovalent and tetravalent
      formulations. In tetravalent formulations, DENV-1 and DENV-2 antagonized each
      other, with a high dose of one decreasing seroconversion to the other. However,
      high-dose DENV-1 significantly increased seroconversion against 3 or more
      serotypes, increasing seroconversion to DENV-1, DENV-3, and DENV-4. The highest
      reactogenicity occurred when DENV-1 was at high dose and all others were low;
      reactogenicity decreased with the incorporation of other high-dose serotypes.
      CONCLUSIONS: Interference and facilitation occurred between serotypes in the live
      vaccine candidate evaluated. These analyses suggest that it may be possible to
      exploit facilitation to increase overall seroconversion.

PMID- 21742845
TI  - Respiratory syncytial virus binds and undergoes transcription in neutrophils from
      the blood and airways of infants with severe bronchiolitis.
AB  - BACKGROUND: Neutrophils are the predominant cell in the lung inflammatory
      infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis.
      Although it has previously been shown that neutrophils from both blood and
      bronchoalveolar lavage (BAL) are activated, little is understood about their role
      in response to RSV infection. This study investigated whether RSV proteins and
      mRNA are present in neutrophils from blood and BAL of infected infants. METHODS:
      We obtained blood and BAL samples from 20 infants with severe RSV bronchiolitis
      and 8 healthy control infants. Neutrophil RSV F, G, and N proteins, RSV N genomic
      RNA, and messenger RNA (mRNA) were quantified. RESULTS: RSV proteins were found
      in BAL and blood neutrophils in infants with RSV disease but not in neutrophils
      from healthy infants. BAL and blood neutrophils from infants with RSV disease,
      but not those from healthy infants, expressed RSV N genomic RNA, indicating
      uptake of whole virus; 17 of 20 BAL and 8 of 9 blood neutrophils from patients
      expressed RSV N mRNA. CONCLUSIONS: This work shows, for the first time, the
      presence of RSV proteins and mRNA transcripts within BAL and blood neutrophils
      from infants with severe RSV bronchiolitis.

PMID- 21742846
TI  - Epidemic sindbis virus infection in Finland: a population-based case-control
      study of risk factors.
AB  - BACKGROUND: Sindbis virus (SINV) is an arthropod-borne alphavirus that causes
      rash and arthritis. In Finland, epidemics occur cyclically, but factors
      associated with clinical SINV infection are largely unknown. We conducted a
      population-based case-control study during the epidemic year 2002. METHODS: SINV
      cases were serologically confirmed and reported to the National Infectious
      Disease Registry. Five control subjects, matched for age, sex, and residence,
      were selected from the National Population Information System. Data were
      collected using a self-administered mail survey. Conditional logistic regression
      models were used to identify independent risk factors; missing data were
      addressed using Bayesian full-likelihood modeling. RESULTS: A total of 337 case
      patients (58% female; age range, 1-94 y) and 934 control subjects were enrolled.
      Reported exposure to mosquito bites (matched odds ratio [mOR], 16.7; 95%
      confidence interval [CI], 9.1-33.4) and spending time in woods or marshland (mOR,
      1.8; 95% CI, 1.3-2.5) were independently associated with SINV infection in the
      multivariable model. The population-attributable risk for mosquito bites was
      87.2%. There were dose-response relations for increased number of insect bites
      (mOR, 23.8-72.5) and increased time spent in woods or marshland (mOR, 1.3-2.2).
      CONCLUSIONS: Educating the public in endemic areas to avoid mosquito exposure and
      use protective measures remain important prevention measures for SINV infection.

PMID- 21742847
TI  - Genetic and functional evidence implicating DLL1 as the gene that influences
      susceptibility to visceral leishmaniasis at chromosome 6q27.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is caused by Leishmania donovani and
      Leishmania infantum chagasi. Genome-wide linkage studies from Sudan and Brazil
      identified a putative susceptibility locus on chromosome 6q27. METHODS: Twenty
      two single-nucleotide polymorphisms (SNPs) at genes PHF10, C6orf70, DLL1,
      FAM120B, PSMB1, and TBP were genotyped in 193 VL cases from 85 Sudanese families,
      and 8 SNPs at genes PHF10, C6orf70, DLL1, PSMB1, and TBP were genotyped in 194 VL
      cases from 80 Brazilian families. Family-based association, haplotype, and
      linkage disequilibrium analyses were performed. Multispecies comparative sequence
      analysis was used to identify conserved noncoding sequences carrying putative
      regulatory elements. Quantitative reverse-transcription polymerase chain reaction
      measured expression of candidate genes in splenic aspirates from Indian patients
      with VL compared with that in the control spleen sample. RESULTS: Positive
      associations were observed at PHF10, C6orf70, DLL1, PSMB1, and TBP in Sudan, but
      only at DLL1 in Brazil (combined P = 3 * 10(-4) at DLL1 across Sudan and Brazil).
      No functional coding region variants were observed in resequencing of 22 Sudanese
      VL cases. DLL1 expression was significantly (P = 2 * 10(-7)) reduced (mean fold
      change, 3.5 [SEM, 0.7]) in splenic aspirates from patients with VL, whereas other
      6q27 genes showed higher levels (1.27 * 10(-6) < P < .01) than did the control
      spleen sample. A cluster of conserved noncoding sequences with putative
      regulatory variants was identified in the distal promoter of DLL1. CONCLUSIONS:
      DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated
      as the chromosome 6q27 VL susceptibility gene.

PMID- 21742848
TI  - Selection of TcII Trypanosoma cruzi population following macrophage infection.
AB  - BACKGROUND: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi,
      which exhibits a high genetic variability. TcI, TcII, or mixed TcI/TcII strains
      may be found during acute human infection while mainly TcII parasites are present
      at the chronic stage of disease. In a previously studied Chagas disease outbreak,
      we identified mixed TcI/TcII strains in the vector Triatoma tibiamaculata and
      only TcII strains in infected humans, indicating that T. cruzi populations may be
      selected within the human host. METHODS: Utilizing molecular typing and cell
      biology techniques, we investigated the interaction of TcI, TcII, and mixed
      TcI/TcII strains with macrophages, an important cell population implicated in
      controlling protozoan infection. RESULTS: TcII but not TcI strains were selected
      by both human and murine macrophages in vitro and by peritoneal cavity cells in
      vivo. Biological analysis revealed that, compared with TcI, TcII strains display
      higher infective and multiplicative ability as well as lower doubling time inside
      macrophages. However, TcI and TcII strains present similar susceptibility to
      interferon-gamma-activated macrophages in vitro. CONCLUSIONS: Taken together, our
      results reveal the existence of an intracellular selection process in macrophages
      that favors TcII, but not TcI, when infection occurs with vector-derived mixed
      TcI/TcII strains.

PMID- 21742849
TI  - The potential pitfalls of targeted screening for acute HIV infection: the view
      from New York City.

PMID- 21742850
TI  - A potential role of indoleamine 2,3-dioxygenase-specific T cells in leishmania
      vaccination.

PMID- 21742851
TI  - Downregulation of interferon-beta in antibody-dependent enhancement of dengue
      viral infections of human macrophages is dependent on interleukin-6.

PMID- 21742856
TI  - Cecembia lonarensis gen. nov., sp. nov., a novel haloalkalitolerant bacterium of
      the family Cyclobacteriaceae, isolated from a haloalkaline lake and emended
      descriptions of the genera Indibacter, Nitritalea, Belliella and Aquiflexum.

PMID- 21742857
TI  - Oceanisphaera arctica sp. nov., isolated from a marine sediment of Kongsfjorden,
      Svalbard, Arctic.

PMID- 21742858
TI  - Cyclobacterium qasimii sp. nov., a psychrotolerant bacterium isolated from a
      marine sediment of Kongsfjorden, Svalbard.

PMID- 21742859
TI  - Stappia aquimarina sp. nov., isolated from seawater.

PMID- 21742860
TI  - Lutibaculum baratangense gen. nov., sp. nov., a novel proteobacterium isolated
      from a mud volcano, Andamans, India.

PMID- 21742861
TI  - The genetic links between the big five personality traits and general interest
      domains.
AB  - This is the first genetically informative study in which multiple informants were
      used to quantify the genetic and environmental sources of individual differences
      in general interests as well as the phenotypic and genetic links between general
      interests and Big Five personality traits. Self-reports and two peer ratings from
      844 individuals, including 225 monozygotic and 113 dizygotic complete twin pairs,
      were collected. Multiple-rater scores (composites) revealed that the averaged
      levels of genetic and environmental effects on seven broad interest domains were
      similar to those on personality traits. Multivariate analyses showed that about
      35% of the genetic and 9% of the environmental variance in interests were
      explained by personality domains, in particular by Openness. The findings suggest
      that interests cannot easily be considered as a byproduct of the interactions
      between personality genotypes and the environmental influences but rather as an
      internal regulation of behavior with an own genetic basis.

PMID- 21742862
TI  - Genome sequence of Rhodococcus sp. strain R04, a polychlorinated-biphenyl
      biodegrader.
AB  - The genus Rhodococcus has proved to be a promising option for the cleanup of
      polluted sites and application of a microbial biocatalyst. Rhodococcus sp. strain
      R04, isolated from oil-contaminated soil, can biodegrade polychlorinated
      biphenyls. Here we report the draft genome sequence of Rhodococcus sp. strain
      R04, which could be used to predict genes for xenobiotic biodegradation and
      provide important insights into the applications of this strain.

PMID- 21742863
TI  - Transcriptional profiling of the iron starvation response in Bordetella pertussis
      provides new insights into siderophore utilization and virulence gene expression.
AB  - Serological studies of patients with pertussis and the identification of
      antigenic Bordetella pertussis proteins support the hypothesis that B. pertussis
      perceives an iron starvation cue and expresses multiple iron source utilization
      systems in its natural human host environment. Furthermore, previous studies
      using a murine respiratory tract infection model showed that several of these B.
      pertussis iron systems are required for colonization and persistence and are
      differentially expressed over the course of infection. The present study examined
      genome-wide changes in B. pertussis gene transcript abundance in response to iron
      starvation in vitro. In addition to known iron source utilization genes, we
      identified a previously uncharacterized iron-repressed cytoplasmic membrane
      transporter system, fbpABC, that is required for the utilization of multiple
      structurally distinct siderophores including alcaligin, enterobactin,
      ferrichrome, and desferrioxamine B. Expression of type III secretion system genes
      was also found to be upregulated during iron starvation in both B. pertussis
      strain Tohama I and Bordetella bronchiseptica strain RB50. In a survey of type
      III secretion system protein production by an assortment of B. pertussis
      laboratory-adapted and low-passage clinical isolate strains, iron limitation
      increased the production and secretion of the type III secretion system-specific
      translocation apparatus tip protein Bsp22 in all Bvg-proficient strains. These
      results indicate that iron starvation in the infected host is an important
      environmental cue influencing not only Bordetella iron transport gene expression
      but also the expression of other important virulence-associated genes.

PMID- 21742864
TI  - Genome sequence of Lactobacillus cypricasei KCTC 13900.
AB  - Lactobacillus cypricasei KCTC 13900 is important in the generation of particular
      flavors and in other ripening processes associated with specific cheeses. Here,
      we announce the draft genome sequence of Lactobacillus cypricasei KCTC 13900,
      isolated from cheeses, and describe major findings from its annotation.

PMID- 21742865
TI  - Legionella pneumophila requires polyamines for optimal intracellular growth.
AB  - The Gram-negative intracellular pathogen Legionella pneumophila replicates in a
      membrane-bound compartment known as the Legionella-containing vacuole (LCV), into
      which it abundantly releases its chaperonin, HtpB. To determine whether HtpB
      remains within the LCV or reaches the host cell cytoplasm, we infected U937 human
      macrophages and CHO cells with L. pneumophila expressing a translocation reporter
      consisting of the Bordetella pertussisa denylate cyclase fused to HtpB. These
      infections led to increased cyclic AMP levels, suggesting that HtpB reaches the
      host cell cytoplasm. To identify potential functions of cytoplasmic HtpB, we
      expressed it in the yeast Saccharomyces cerevisiae, where HtpB induced
      pseudohyphal growth. A yeast-two-hybrid screen showed that HtpB interacted with S
      adenosylmethionine decarboxylase (SAMDC), an essential yeast enzyme (encoded by
      SPE2) that is required for polyamine biosynthesis. Increasing the copy number of
      SPE2 induced pseudohyphal growth in S. cerevisiae; thus, we speculated that (i)
      HtpB induces pseudohyphal growth by activating polyamine synthesis and (ii) L.
      pneumophila may require exogenous polyamines for growth. A pharmacological
      inhibitor of SAMDC significantly reduced L. pneumophila replication in L929 mouse
      cells and U937 macrophages, whereas exogenously added polyamines moderately
      favored intracellular growth, confirming that polyamines and host SAMDC activity
      promote L. pneumophila proliferation. Bioinformatic analysis revealed that most
      known enzymes required for polyamine biosynthesis in bacteria (including SAMDC)
      are absent in L. pneumophila, further suggesting a need for exogenous polyamines.
      We hypothesize that HtpB may function to ensure a supply of polyamines in host
      cells, which are required for the optimal intracellular growth of L. pneumophila.

PMID- 21742866
TI  - TrbB from conjugative plasmid F is a structurally distinct disulfide isomerase
      that requires DsbD for redox state maintenance.
AB  - TrbB, a periplasmic protein encoded by the conjugative plasmid F, has a predicted
      thioredoxin-like fold and possesses a C-X-X-C redox active site motif. TrbB may
      function in the conjugative process by serving as a disulfide bond isomerase,
      facilitating proper folding of a subset of F-plasmid-encoded proteins in the
      periplasm. Previous studies have demonstrated that a DeltatrbB F plasmid in
      Escherichia coli lacking DsbC(E.coli), its native disulfide bond isomerase,
      experiences a 10-fold decrease in mating efficiency but have not provided direct
      evidence for disulfide bond isomerase activity. Here we demonstrate that trbB can
      partially restore transfer of a variant of the distantly related R27 plasmid when
      both chromosomal and plasmid genes encoding disulfide bond isomerases have been
      disrupted. In addition, we show that TrbB displays both disulfide bond isomerase
      and reductase activities on substrates not involved in the conjugative process.
      Unlike canonical members of the disulfide bond isomerase family, secondary
      structure predictions suggest that TrbB lacks both an N-terminal dimerization
      domain and an alpha-helical domain found in other disulfide bond isomerases.
      Phylogenetic analyses support the conclusion that TrbB belongs to a unique family
      of plasmid-based disulfide isomerases. Interestingly, although TrbB diverges
      structurally from other disulfide bond isomerases, we show that like those
      isomerases, TrbB relies on DsbD from E. coli for maintenance of its C-X-X-C redox
      active site motif.

PMID- 21742867
TI  - RNase III-dependent expression of the rpsO-pnp operon of Streptomyces coelicolor.
AB  - We have examined the expression of the rpsO-pnp operon in an RNase III (rnc)
      mutant of Streptomyces coelicolor. Western blotting demonstrated that
      polynucleotide phosphorylase (PNPase) levels increased in the rnc mutant,
      JSE1880, compared with the parental strain, M145, and this observation was
      confirmed by polymerization assays. It was observed that rpsO-pnp mRNA levels
      increased in the rnc mutant by 1.6- to 4-fold compared with M145. This increase
      was observed in exponential, transition, and stationary phases, and the levels of
      the readthrough transcript, initiated upstream of rpsO in the rpsO-pnp operon;
      the pnp transcript, initiated in the rpsO-pnp intergenic region; and the rpsO
      transcript all increased. The increased levels of these transcripts in JSE1880
      reflected increased chemical half-lives for each of the three. We demonstrated
      further that overexpression of the rpsO-pnp operon led to significantly higher
      levels of PNPase activity in JSE1880 compared to M145, reflecting the likelihood
      that PNPase expression is autoregulated in an RNase III-dependent manner in S.
      coelicolor. To explore further the increase in the level of the pnp transcript
      initiated in the intergenic region in JSE1880, we utilized that transcript as a
      substrate in assays employing purified S. coelicolor RNase III. These assays
      revealed the presence of hitherto-undiscovered sites of RNase III cleavage of the
      pnp transcript. The position of those sites was determined by primer extension,
      and they were shown to be situated in the loops of a stem-loop structure.

PMID- 21742868
TI  - Genome sequence of a porcine extraintestinal pathogenic Escherichia coli strain.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) is an important pathogen
      which can infect humans and animals and cause many diseases outside the
      intestine. Here, we report the first draft genome sequence of a porcine ExPEC
      strain, PCN033, isolated from a pig with meningitis.

PMID- 21742869
TI  - Draft genome sequence of the polycyclic aromatic hydrocarbon-degrading,
      genetically engineered bioluminescent bioreporter Pseudomonas fluorescens HK44.
AB  - Pseudomonas fluorescens strain HK44 (DSM 6700) is a genetically engineered lux
      based bioluminescent bioreporter. Here we report the draft genome sequence of
      strain HK44. Annotation of ~6.1 Mb of sequence indicates that 30% of the traits
      are unique and distributed over five genomic islands, a prophage, and two
      plasmids.

PMID- 21742870
TI  - Overexpression of LolCDE allows deletion of the Escherichia coli gene encoding
      apolipoprotein N-acyltransferase.
AB  - Bacterial lipoproteins represent a subset of membrane-associated proteins that
      are covalently modified with lipids at the N-terminal cysteine. The final step of
      lipoprotein modification, N-acylation of apolipoproteins, is mediated by
      apolipoprotein N-acyltransferase (Lnt). Examinations with reconstituted
      proteoliposomes and a conditional mutant previously indicated that N-acylation of
      lipoproteins is required for their efficient release from the inner membrane
      catalyzed by LolA and LolCDE, the lipoprotein-specific chaperone and ABC
      transporter, respectively. Because Lnt is essential for Escherichia coli, a
      mutant lacking Lnt activity has not been isolated. However, we report here that
      lnt-null strains can be constructed when LolCDE is overproduced in strains
      lacking either the major outer membrane lipoprotein Lpp or transpeptidases that
      cross-link Lpp with peptidoglycan. Lipoproteins purified from the lnt-null strain
      exhibited increased mobility on SDS-PAGE compared to those from wild-type cells
      and could be sequenced by Edman degradation, indicating that lipoproteins in this
      mutant exist as apolipoproteins that lack N-acylation. Overexpression of Lpp in
      the lnt-null strain resulted in the accumulation of apoLpp in the inner membrane
      and caused growth arrest. In contrast to the release of mature Lpp in the
      presence of LolA and LolCDE, that of apoLpp from the inner membrane was
      significantly retarded. Furthermore, the amount of lipoproteins copurified with
      LolCDE was significantly reduced in the lnt-null strain. These results indicate
      that the affinity of LolCDE for apolipoprotein is very low, and therefore,
      overexpression of LolCDE is required for its release and sorting to the outer
      membrane.

PMID- 21742871
TI  - Complete genome sequence of the commensal Streptococcus salivarius strain
      JIM8777.
AB  - The commensal bacterium Streptococcus salivarius is a prevalent species of the
      human oropharyngeal tract with an important role in oral ecology. Here, we report
      the complete 2.2-Mb genome sequence and annotation of strain JIM8777, which was
      recently isolated from the oral cavity of a healthy, dentate infant.

PMID- 21742872
TI  - Genome sequence of the nonpathogenic Listeria monocytogenes serovar 4a strain M7.
AB  - This report presents the complete and annotated genome sequence of the naturally
      nonpathogenic Listeria monocytogenes serovar 4a strain M7, isolated from cow's
      milk in Zhejiang province, China.

PMID- 21742873
TI  - Genome sequence of Lactobacillus ruminis SPM0211, isolated from a fecal sample
      from a healthy Korean.
AB  - Lactobacillus ruminis SPM0211 is a potential probiotic strain that shows
      antimicrobial activity against emerging pathogens. Here we present the draft
      genomic sequence of L. ruminis SPM0211, isolated from a fecal sample from a
      healthy Korean and describe both the common and unique features of this strain.

PMID- 21742874
TI  - The danger of annotation by analogy: most "thiI" genes play no role in thiamine
      biosynthesis.

PMID- 21742875
TI  - Genome sequence of the newly isolated chemolithoautotrophic Bradyrhizobiaceae
      strain SG-6C.
AB  - Strain SG-6C (DSM 23264, CCM 7827) is a chemolithoautotrophic bacterium of the
      family Bradyrhizobiaceae. It can also grow heterotrophically under appropriate
      environmental conditions. Here we report the annotated genome sequence of this
      strain in a single 4.3-Mb circular scaffold.

PMID- 21742876
TI  - Genome sequence of Rheinheimera sp. strain A13L, isolated from Pangong Lake,
      India.
AB  - Rheinheimera sp. strain A13L, which has antimicrobial activity, was isolated from
      alkaline brackish water of the high-altitude Pangong Lake of Ladakh, India. Here
      we report the draft genome sequence of Rhienheimera sp. strain A13L (4,523,491 bp
      with a G+C content of 46.23%). The genome is predicted to contain genes for
      marinocine and colicin V production, which may be responsible for the
      antimicrobial activity of the strain.

PMID- 21742877
TI  - Genome sequence of Mycoplasma ovipneumoniae strain SC01.
AB  - Mycoplasma ovipneumoniae is associated with chronic nonprogressive pneumonia in
      both sheep and goats. Studies concerning its molecular pathogenesis, genetic
      analysis, and vaccine development have been hindered due to limited genomic
      information. Here, we announce the first complete genome sequence of this
      organism.

PMID- 21742878
TI  - Draft genome sequence of the Paenibacillus polymyxa type strain (ATCC 842T), a
      plant growth-promoting bacterium.
AB  - Paenibacillus polymyxa is an endospore-forming Gram-positive soil bacterium that
      is well-known for its ability to promote plant growth. Here we report the draft
      genome sequence of P. polymyxa ATCC 842(T), the type strain of the species P.
      polymyxa, and the family Paenibacillaceae. The P. polymyxa genome contains a
      repertoire of biosynthetic genes for antibiotics and hydrolytic enzymes that
      account for its beneficial effects in the rhizosphere to the host plants it
      associates with.

PMID- 21742879
TI  - Genome sequence of the rice-pathogenic bacterium Acidovorax avenae subsp. avenae
      RS-1.
AB  - Acidovorax avenae subsp. avenae is a phytobacterium which is the causative agent
      of several plant diseases with economic significance. Here, we present the draft
      genome sequence of strain RS-1, which was isolated from rice shoots in a rice
      field in China. This strain can cause bacterial stripe of rice.

PMID- 21742880
TI  - Draft genome sequence of Gordonia neofelifaecis NRRL B-59395, a cholesterol
      degrading actinomycete.
AB  - We report a draft sequence of the genome of Gordonia neofelifaecis NRRL B-59395,
      a cholesterol-degrading actinomycete isolated from fresh feces of a clouded
      leopard (Neofelis nebulosa). As predicted, the reported genome contains several
      gene clusters for cholesterol degradation. This is the second available genome
      sequence of the family Gordoniaceae.

PMID- 21742881
TI  - Complete genome sequence of Bifidobacterium longum subsp. longum KACC 91563.
AB  - Bifidobacterium longum strains predominate in the colonic microbiota of breast
      fed infants. Here we report the complete genome sequence of B. longum subsp.
      longum KACC 91563, isolated from feces of neonates. A single circular chromosome
      of 2,385,301 bp contains 1,980 protein-coding genes, 56 tRNA genes, and 3 rRNA
      operons.

PMID- 21742882
TI  - YuaB functions synergistically with the exopolysaccharide and TasA amyloid fibers
      to allow biofilm formation by Bacillus subtilis.
AB  - During biofilm formation by Bacillus subtilis, two extracellular matrix
      components are synthesized, namely, the TasA amyloid fibers and an
      exopolysaccharide. In addition, a small protein called YuaB has been shown to
      allow the biofilm to form. The regulatory protein DegU is known to initiate
      biofilm formation. In this report we show that the main role of DegU during
      biofilm formation is to indirectly drive the activation of transcription from the
      yuaB promoter. The N terminus of YuaB constitutes a signal peptide for the Sec
      transport system. Here we show that the presence of the signal peptide is
      required for YuaB function. In addition we demonstrate that upon export of YuaB
      from the cytoplasm, it localizes to the cell wall. We continue with evidence that
      increased production of TasA and the exopolysaccharide is not sufficient to
      overcome the effects of a mutation in yuaB, demonstrating the unique involvement
      of YuaB in forming a biofilm. In line with this, YuaB is not involved in correct
      synthesis, export, or polymerization of either the TasA amyloid fibers or the
      exopolysaccharide. Taken together, these findings identify YuaB as a protein that
      plays a novel role during biofilm formation. We hypothesize that YuaB functions
      synergistically with the known components of the biofilm matrix to facilitate the
      assembly of the biofilm matrix.

PMID- 21742883
TI  - Complete genome sequences of the chemolithoautotrophic Oligotropha
      carboxidovorans strains OM4 and OM5.
AB  - We report on genome sequencing of Oligotropha carboxidovorans strain OM4 and
      resequencing of strain OM5. The genomes of both are composed of one chromosome
      and two plasmids. The presence of two plasmids in the OM5 genome is inconsistent
      with the previously published sequence, for which only one plasmid was described
      (D. Paul, S. Bridges, S. Burgess, Y. Dandass, and M. Lawrence, BMC Genomics
      11:511, 2010).

PMID- 21742884
TI  - Whole-genome sequence of a multidrug-resistant clinical isolate of Acinetobacter
      lwoffii.
AB  - Acinetobacter lwoffii has been considered an opportunistic pathogen that can
      cause nosocomial infections in humans. Here, we present the genome sequence of A.
      lwoffii WJ10621, a multidrug-resistant clinical isolate that carries a plasmid
      with the NDM-1 resistance gene.

PMID- 21742885
TI  - Genome sequence of Ruegeria sp. strain KLH11, an N-acylhomoserine lactone
      producing bacterium isolated from the marine sponge Mycale laxissima.
AB  - Ruegeria sp. strain KLH11, isolated from the marine sponge Mycale laxissima,
      produces a complex profile of N-acylhomoserine lactone quorum-sensing (QS)
      molecules. The genome sequence provides insights into the genetic potential of
      KLH11 to maintain complex QS systems, and this is the first genome report of a
      cultivated symbiont from a marine sponge.

PMID- 21742886
TI  - Genome sequence of Lactobacillus johnsonii PF01, isolated from piglet feces.
AB  - Lactobacillus johnsonii PF01, an autochthonous bacterium of the gastrointestinal
      tract, was isolated from a fecal sample from a piglet. The strain adhered
      specifically to the duodenal and jejunal epithelial cells of the piglet and had
      high bile resistance activity. Here we report the genomic sequence of L.
      johnsonii PF01.

PMID- 21742887
TI  - Genome sequence of Idiomarina sp. strain A28L, isolated from Pangong Lake, India.
AB  - Idiomarina sp. strain A28L was isolated from the alkaline brackish water of a
      high-altitude lake, Pangong Lake. Here, we present the draft genome of Idiomarina
      sp. strain A28L, which contains 2,591,567 bp with a G+C content of 45.5 mol% and
      contains 2,299 protein-coding genes and 56 structural RNAs.

PMID- 21742888
TI  - Genome sequences of Alicycliphilus denitrificans strains BC and K601T.
AB  - Alicycliphilus denitrificans strain BC and A. denitrificans strain K601(T)
      degrade cyclic hydrocarbons. These strains have been isolated from a mixture of
      wastewater treatment plant material and benzene-polluted soil and from a
      wastewater treatment plant, respectively, suggesting their role in bioremediation
      of soil and water. Although the strains are phylogenetically closely related,
      there are some clear physiological differences. The hydrocarbon cyclohexanol, for
      example, can be degraded by strain K601(T) but not by strain BC. Furthermore,
      both strains can use nitrate and oxygen as an electron acceptor, but only strain
      BC can use chlorate as electron acceptor. To better understand the nitrate and
      chlorate reduction mechanisms coupled to the oxidation of cyclic compounds, the
      genomes of A. denitrificans strains BC and K601(T) were sequenced. Here, we
      report the complete genome sequences of A. denitrificans strains BC and K601(T).

PMID- 21742889
TI  - Draft genome sequence of Lactobacillus mali KCTC 3596.
AB  - We announce the draft genome sequence of the type strain Lactobacillus mali KCTC
      3596 (2,652,969 bp, with a G+C content of 36.0%), which is one of the most
      prevalent lactic acid bacteria present during the manufacturing process of apple
      juice. The genome consists of 122 large contigs (>100 bp). All of the contigs
      were assembled by Newbler Assembler 2.3 (454 Life Science).

PMID- 21742890
TI  - Complete genome sequence of the type strain Cupriavidus necator N-1.
AB  - Here we announce the complete genome sequence of the copper-resistant bacterium
      Cupriavidus necator N-1, the type strain of the genus Cupriavidus. The genome
      consists of two chromosomes and two circular plasmids. Based on genome
      comparison, the chromosomes of C. necator N-1 share a high degree of similarity
      with the two chromosomal replicons of the bioplastic-producing hydrogen bacterium
      Ralstonia eutropha H16. The two strains differ in their plasmids and the presence
      of hydrogenase genes, which are absent in strain N-1.

PMID- 21742891
TI  - Complete genome sequence of Clostridium acetobutylicum DSM 1731, a solvent
      producing strain with multireplicon genome architecture.
AB  - Clostridium acetobutylicum is an important microorganism for solvent production.
      We report the complete genome sequence of C. acetobutylicum DSM 1731, a genome
      with multireplicon architecture. Comparison with the sequenced type strain C.
      acetobutylicum ATCC 824, the genome of strain DSM1731 harbors a 1.7-kb insertion
      and a novel 11.1-kb plasmid, which might have been acquired during evolution.

PMID- 21742892
TI  - KefF, the regulatory subunit of the potassium efflux system KefC, shows quinone
      oxidoreductase activity.
AB  - Escherichia coli and many other Gram-negative pathogenic bacteria protect
      themselves from the toxic effects of electrophilic compounds by using a potassium
      efflux system (Kef). Potassium efflux is coupled to the influx of protons, which
      lowers the internal pH and results in immediate protection. The activity of the
      Kef system is subject to complex regulation by glutathione and its S conjugates.
      Full activation of KefC requires a soluble ancillary protein, KefF. This protein
      has structural similarities to oxidoreductases, including human quinone
      reductases 1 and 2. Here, we show that KefF has enzymatic activity as an
      oxidoreductase, in addition to its role as the KefC activator. It accepts NADH
      and NADPH as electron donors and quinones and ferricyanide (in addition to other
      compounds) as acceptors. However, typical electrophilic activators of the Kef
      system, e.g., N-ethyl maleimide, are not substrates. If the enzymatic activity is
      disrupted by site-directed mutagenesis while retaining structural integrity, KefF
      is still able to activate the Kef system, showing that the role as an activator
      is independent of the enzyme activity. Potassium efflux assays show that
      electrophilic quinones are able to activate the Kef system by forming S
      conjugates with glutathione. Therefore, it appears that the enzymatic activity of
      KefF diminishes the redox toxicity of quinones, in parallel with the protection
      afforded by activation of the Kef system.

PMID- 21742893
TI  - Genome sequence of Lactobacillus salivarius GJ-24, a probiotic strain isolated
      from healthy adult intestine.
AB  - The draft genome sequence of Lactobacillus salivarius GJ-24 isolated from the
      feces of healthy adults was determined. Its properties, including milk
      fermentation activity and bacteriocin production, suggest its potential uses as a
      probiotic lactic acid bacterium and start culture for dairy products.

PMID- 21742894
TI  - Complete genome sequence of the clinical Streptococcus salivarius strain CCHSS3.
AB  - Streptococcus salivarius is a commensal species commonly found in the human oral
      cavity and digestive tract, although it is also associated with human infections
      such as meningitis, endocarditis, and bacteremia. Here, we report the complete
      sequence of S. salivarius strain CCHSS3, isolated from human blood.

PMID- 21742895
TI  - Unnecessary signaling: poorly named?

PMID- 21742896
TI  - Contributions of five secondary metal uptake systems to metal homeostasis of
      Cupriavidus metallidurans CH34.
AB  - Cupriavidus metallidurans is adapted to high concentrations of transition metal
      cations and is a model system for studying metal homeostasis in difficult
      environments. The elemental composition of C. metallidurans cells cultivated
      under various conditions was determined, revealing the ability of the bacterium
      to shield homeostasis of one essential metal from the toxic action of another.
      The contribution of metal uptake systems to this ability was studied. C.
      metallidurans contains three CorA members of the metal inorganic transport (MIT)
      protein family of putative magnesium uptake systems, ZupT of the ZRT/IRT protein,
      or ZIP, family, and PitA, which imports metal phosphate complexes. Expression of
      the genes for all these transporters was regulated by zinc availability, as shown
      by reporter gene fusions. While expression of zupT was upregulated under
      conditions of zinc starvation, expression of the other genes was downregulated at
      high zinc concentrations. Only corA(1) expression was influenced by magnesium
      starvation. Deletion mutants were constructed to characterize the contribution of
      each system to transition metal import. This identified ZupT as the main zinc
      uptake system under conditions of low zinc availability, CorA(1) as the main
      secondary magnesium uptake system, and CorA(2) and CorA(3) as backup systems for
      metal cation import. PitA may function as a cation-phosphate uptake system, the
      main supplier of divalent metal cations and phosphate in phosphate-rich
      environments. Thus, metal homeostasis in C. metallidurans is achieved by highly
      redundant metal uptake systems, which have only minimal cation selectivity and
      are in combination with efflux systems that "worry later" about surplus cations.

PMID- 21742897
TI  - Genome sequence of the ethanol-producing Zymomonas mobilis subsp. pomaceae
      lectotype strain ATCC 29192.
AB  - Zymomonas mobilis is an alphaproteobacterium studied for bioethanol production.
      Different strains of this organism have been hitherto sequenced; they all belong
      to the Z. mobilis subsp. mobilis taxon. Here we report the finished and annotated
      genome sequence of strain ATCC 29192, a cider-spoiling agent isolated in the
      United Kingdom. ATCC 29192 is the lectotype of the second-best-characterized
      subspecies of Z. mobilis, Z. mobilis subsp. pomaceae. The nucleotide sequence of
      ATCC 29192 deviates from that of Z. mobilis subsp. mobilis representatives, which
      justifies its distinct taxonomic positioning and proves particularly useful for
      comparative and functional genomic analyses.

PMID- 21742898
TI  - Pharmacokinetic optimization of 4-substituted methoxybenzoyl-aryl-thiazole and 2
      aryl-4-benzoyl-imidazole for improving oral bioavailability.
AB  - Microtubules are critical components of the cytoskeleton. Perturbing their
      function arrests the growth of a broad spectrum of cancer cell lines, making
      microtubules an excellent and established target for chemotherapy. All of the
      U.S. Food and Drug Administration-approved antitubulin agents bind to paclitaxel
      or vinblastine binding sites in tubulin. Because of the complexity of their
      structures, it is difficult to structurally modify the vinca alkaloids and
      taxanes and develop orally bioavailable agents. Antitubulin agents that target
      the colchicine-binding site in tubulin may provide a better opportunity to be
      developed for oral use because of their relatively simple structures and
      physicochemical properties. A potent antitubulin agent, 4-(3,4,5
      trimethoxybenzoyl)-2-phenyl-thiazole (SMART-H), binding to the colchicine-binding
      site, was discovered in our laboratory. However, the bioavailability of SMART-H
      was low because of its poor solubility. Structural modification of SMART-H led to
      the development of 2-aryl-4-benzoyl-imidazole analog (ABI-274), with improved
      bioavailability and potency but still considerable first-pass metabolism. A
      chlorine derivative (ABI-286), replacing the methyl site of ABI-274, resulted in
      1.5-fold higher metabolic stability in vitro and 1.8-fold lower clearance in rats
      in vivo, indicating that metabolic stability of ABI-274 can be extended by
      blocking benzylic hydroxylation. Overall, ABI-274 and ABI-286 provided 2.4- and
      5.5-fold increases in exposure (area under the curve) after oral dosing in rats
      compared with SMART-H. Most importantly, the structural modifications did not
      compromise potency. ABI-286 exhibited moderate clearance, moderate volume of
      distribution, and acceptable oral bioavailability. This study provided the first
      evidence that ABI-286 may be the first member of a new class of orally
      bioavailable antitubulin agents.

PMID- 21742899
TI  - Mechanisms of reduced maternal and fetal lopinavir exposure in a rat model of
      gestational diabetes.
AB  - Lopinavir (LPV) is the preferred HIV protease inhibitor in pregnancy, but it is
      unknown if gestational diabetes mellitus (GDM) affects its disposition. Hepatic
      protein expression and plasma protein binding are altered in rodent models of
      GDM. Because LPV is influenced by hepatic transporters and metabolic enzymes and
      is highly protein bound, it was hypothesized that streptozotocin-induced GDM
      would alter its disposition. Maternal and fetal tissues were collected from GDM
      rats and controls 45 min after LPV injection. In another cohort, fetuses were
      serially extracted 5 to 60 min after injection. LPV was quantified using liquid
      chromatography tandem mass spectrometry. Expression of relevant transporters,
      such as Multidrug resistance protein 1 (Mdr1), and cytochrome P450 3a2 (Cyp3a2),
      which metabolizes LPV in rodents, was measured in maternal liver via quantitative
      reverse transcriptase polymerase chain reaction and Western blot analysis.
      Expression of relevant transporters also was measured in placenta via
      quantitative reverse transcriptase polymerase chain reaction. Protein binding was
      determined by ultrafiltration. Relative to controls, we observed dramatically
      reduced maternal and fetal LPV exposure in GDM. Compared with controls, maternal
      hepatic Mdr1 and Cyp3a2 were up-regulated, and protein binding was reduced in the
      GDM group. Increased Mdr1- and Cyp3a2-mediated hepatobiliary clearance, coupled
      with a larger unbound LPV fraction, is likely to have facilitated hepatic
      elimination, thereby decreasing maternal and fetal exposure. Not surprisingly, up
      regulation of Mdr1 and Cyp3a2's transcriptional regulator, pregnane X receptor,
      was demonstrated in maternal liver via Western blot analysis. Up-regulation of
      Mdr1 in placentas isolated from the GDM group likely also contributed to
      decreased fetal exposure to LPV. This study provides preclinical support for an
      as yet unreported drug-disease (LPV-GDM) interaction.

PMID- 21742900
TI  - Significant species difference in amide hydrolysis of GDC-0834, a novel potent
      and selective Bruton's tyrosine kinase inhibitor.
AB  - (R)-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5
      dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2
      carboxamide (GDC-0834) is a potent and selective inhibitor of Bruton's tyrosine
      kinase (BTK), investigated as a potential treatment for rheumatoid arthritis. In
      vitro metabolite identification studies in hepatocytes revealed predominant
      formation of an inactive metabolite (M1) via amide hydrolysis in human. The
      formation of M1 appeared to be NADPH-independent in human liver microsomes. M1
      was found in only minor to moderate quantities in plasma from preclinical species
      dosed with GDC-0834. Human clearance predictions using various methodologies
      resulted in estimates ranging from low to high. In addition, GDC-0834 exhibited
      low clearance in PXB chimeric mice with humanized liver. Uncertainty in human
      pharmacokinetic prediction and high interest in a BTK inhibitor for clinical
      evaluation prompted an investigational new drug strategy, in which GDC-0834 was
      rapidly advanced to a single-dose human clinical trial. GDC-0834 plasma
      concentrations in humans were below the limit of quantitation (<1 ng/ml) in most
      samples from the cohorts dosed orally at 35 and 105 mg. In contrast, substantial
      plasma concentrations of M1 were observed. In human plasma and urine, only M1 and
      its sequential metabolites were identified. The formation kinetics of M1 was
      evaluated in rat, dog, monkey, and human liver microsomes in the absence of
      NADPH. The maximum rate of M1 formation (V(max)) was substantially higher in
      human compared with that in other species. In contrast, the Michaelis-Menten
      constant (K(m)) was comparable among species. Intrinsic clearance (V(max)/K(m))
      of GDC-0834 from M1 formation in human was 23- to 169-fold higher than observed
      in rat, dog, and monkey.

PMID- 21742901
TI  - Genetic and biochemical map for the biosynthesis of occidiofungin, an antifungal
      produced by Burkholderia contaminans strain MS14.
AB  - A striking feature of Burkholderia contaminans strain MS14 is the production of a
      glycolipopeptide named occidiofungin. Occidiofungin has a broad range of
      antifungal activities against plant and animal pathogens. In this study, a
      complete covalent structure characterization and identification of the whole
      genomic DNA region for the occidiofungin gene (ocf) cluster are described.
      Discovery of the presence of 2,4-diaminobutyric acid and 3-chloro-beta
      hydroxytyrosine and elucidation of the structure of a novel C(18) fatty amino
      acid residue have been achieved. In addition, seven additional putative open
      reading frames (the genes from ocfI to ocfN [ocfI-N] and ORF16) were identified.
      Transcription of all the putative genes ocfI-N identified in the region except
      ORF16 was regulated by both ambR1 and ambR2. Elucidation of the structure and the
      ocf gene cluster provides insight into the biosynthesis of occidiofungin and
      promotes future aims at understanding the biosynthetic machinery. This work
      provides new avenues for optimizing the production and synthesis of structural
      analogs of occidiofungin.

PMID- 21742902
TI  - Determining the extremes of the cellular NAD(H) level by using an Escherichia
      coli NAD(+)-auxotrophic mutant.
AB  - NAD (NAD(+)) and its reduced form (NADH) are omnipresent cofactors in biological
      systems. However, it is difficult to determine the extremes of the cellular
      NAD(H) level in live cells because the NAD(+) level is tightly controlled by a
      biosynthesis regulation mechanism. Here, we developed a strategy to determine the
      extreme NAD(H) levels in Escherichia coli cells that were genetically engineered
      to be NAD(+) auxotrophic. First, we expressed the ntt4 gene encoding the NAD(H)
      transporter in the E. coli mutant YJE001, which had a deletion of the nadC gene
      responsible for NAD(+) de novo biosynthesis, and we showed NTT4 conferred on the
      mutant strain better growth in the presence of exogenous NAD(+). We then
      constructed the NAD(+)-auxotrophic mutant YJE003 by disrupting the essential gene
      nadE, which is responsible for the last step of NAD(+) biosynthesis in cells
      harboring the ntt4 gene. The minimal NAD(+) level was determined in M9 medium in
      proliferating YJE003 cells that were preloaded with NAD(+), while the maximal
      NAD(H) level was determined by exposing the cells to high concentrations of
      exogenous NAD(H). Compared with supplementation of NADH, cells grew faster and
      had a higher intracellular NAD(H) level when NAD(+) was fed. The intracellular
      NAD(H) level increased with the increase of exogenous NAD(+) concentration, until
      it reached a plateau. Thus, a minimal NAD(H) level of 0.039 mM and a maximum of
      8.49 mM were determined, which were 0.044* and 9.6* those of wild-type cells,
      respectively. Finally, the potential application of this strategy in
      biotechnology is briefly discussed.

PMID- 21742903
TI  - Volatile compound fingerprinting of mixed-culture fermentations.
AB  - With the advent of the -omics era, classical technology platforms, such as
      hyphenated mass spectrometry, are currently undergoing a transformation toward
      high-throughput application. These novel platforms yield highly detailed
      metabolite profiles in large numbers of samples. Such profiles can be used as
      fingerprints for the accurate identification and classification of samples as
      well as for the study of effects of experimental conditions on the concentrations
      of specific metabolites. Challenges for the application of these methods lie in
      the acquisition of high-quality data, data normalization, and data mining. Here,
      a high-throughput fingerprinting approach based on analysis of headspace
      volatiles using ultrafast gas chromatography coupled to time of flight mass
      spectrometry (ultrafast GC/TOF-MS) was developed and evaluated for classification
      and screening purposes in food fermentation. GC-MS mass spectra of headspace
      samples of milk fermented by different mixed cultures of lactic acid bacteria
      (LAB) were collected and preprocessed in MetAlign, a dedicated software package
      for the preprocessing and comparison of liquid chromatography (LC)-MS and GC-MS
      data. The Random Forest algorithm was used to detect mass peaks that
      discriminated combinations of species or strains used in fermentations. Many of
      these mass peaks originated from key flavor compounds, indicating that the
      presence or absence of individual strains or combinations of strains
      significantly influenced the concentrations of these components. We demonstrate
      that the approach can be used for purposes like the selection of strains from
      collections based on flavor characteristics and the screening of (mixed) cultures
      for the presence or absence of strains. In addition, we show that strain-specific
      flavor characteristics can be traced back to genetic markers when comparative
      genome hybridization (CGH) data are available.

PMID- 21742904
TI  - Investigation of the electron transport chain to and the catalytic activity of
      the diheme cytochrome c peroxidase CcpA of Shewanella oneidensis.
AB  - Bacterial diheme c-type cytochrome peroxidases (BCCPs) catalyze the periplasmic
      reduction of hydrogen peroxide to water. The gammaproteobacterium Shewanella
      oneidensis produces the peroxidase CcpA under a number of anaerobic conditions,
      including dissimilatory iron-reducing conditions. We wanted to understand the
      function of this protein in the organism and its putative connection to the
      electron transport chain to ferric iron. CcpA was isolated and tested for
      peroxidase activity, and its structural conformation was analyzed by X-ray
      crystallography. CcpA exhibited in vitro peroxidase activity and had a structure
      typical of diheme peroxidases. It was produced in almost equal amounts under
      anaerobic and microaerophilic conditions. With 50 mM ferric citrate and 50 MUM
      oxygen in the growth medium, CcpA expression results in a strong selective
      advantage for the cell, which was detected in competitive growth experiments with
      wild-type and DeltaccpA mutant cells that lack the entire ccpA gene due to a
      markerless deletion. We were unable to reduce CcpA directly with CymA, MtrA, or
      FccA, which are known key players in the chain of electron transport to ferric
      iron and fumarate but identified the small monoheme ScyA as a mediator of
      electron transport between CymA and BCCP. To our knowledge, this is the first
      detailed description of a complete chain of electron transport to a periplasmic c
      type cytochrome peroxidase. This study furthermore reports the possibility of
      establishing a specific electron transport chain using c-type cytochromes.

PMID- 21742905
TI  - Creation of a cellooligosaccharide-assimilating Escherichia coli strain by
      displaying active beta-glucosidase on the cell surface via a novel anchor
      protein.
AB  - We demonstrated direct assimilation of cellooligosaccharide using Escherichia
      coli displaying beta-glucosidase (BGL). BGL from Thermobifida fusca YX (Tfu0937)
      was displayed on the E. coli cell surface using a novel anchor protein named Blc.
      This strain was grown successfully on 0.2% cellobiose, and the optical density at
      600 nm (OD(600)) was 1.05 after 20 h.

PMID- 21742906
TI  - Amoeba host model for evaluation of Streptococcus suis virulence.
AB  - The Gram-positive bacterium Streptococcus suis is a major swine pathogen
      worldwide that causes meningitis, septicemia, and endocarditis. In this study, we
      demonstrate that the amoeba Dictyostelium discoideum can be a relevant
      alternative system to study the virulence of S. suis.

PMID- 21742907
TI  - Novel antiphytopathogenic compound 2-heptyl-5-hexylfuran-3-carboxylic acid,
      produced by newly isolated Pseudomonas sp. strain SJT25.
AB  - Pseudomonas sp. strain SJT25, which strongly antagonizes plant pathogens, was
      isolated from rice rhizosphere soil by a bioactivity-guided approach. A novel
      antiphytopathogenic compound was isolated from the fermentation broth of
      Pseudomonas sp. SJT25 and identified as 2-heptyl-5-hexylfuran-3-carboxylic acid.
      This compound showed antimicrobial activities both in vitro and in vivo.

PMID- 21742908
TI  - L-arabitol is the actual inducer of xylanase expression in Hypocrea jecorina
      (Trichoderma reesei).
AB  - The saprophytic fungus Hypocrea jecorina (anamorph, Trichoderma reesei) is an
      important native producer of hydrolytic enzymes, including xylanases. Regarding
      principles of sustainability, cheap and renewable raw materials, such as d-xylose
      (the backbone monomer of xylan), have been receiving increasing attention from
      industries. Recently, it was demonstrated that small (0.5 to 1 mM) amounts of d
      xylose induce the highest expression of xylanase in H. jecorina. However, it was
      also reported that active metabolism of d-xylose is necessary for induction. In
      this report, we demonstrate that xylitol, the next intermediate in the pentose
      pathway after d-xylose, does not trigger transcription of xylanase-encoding genes
      in H. jecorina QM9414. The highest level of transcription of xylanolytic enzyme
      encoding genes occurred in an xdh1 (encoding a xylitol dehydrogenase) deletion
      strain cultured in the presence of 0.5 mM d-xylose, suggesting that a metabolite
      upstream of xylitol is the inducer. The expression levels of xylanases in an xdh1
      lad1 double-deletion strain were lower than that of an xdh1 deletion strain. This
      observation suggested that l-xylulose is not an inducer and led to the hypothesis
      that l-arabitol is the actual inducer of xylanase expression. A direct comparison
      of transcript levels following the incubation of the H. jecorina parental strain
      with various metabolites of the pentose pathway confirmed this hypothesis. In
      addition, we demonstrate that xyr1, the activator gene, is not induced in the
      presence of pentose sugars and polyols, regardless of the concentration used;
      instead, we observed low constitutive expression of xyr1.

PMID- 21742909
TI  - Functionally redundant cellobiose-degrading soil bacteria respond differentially
      to oxygen.
AB  - The availability of oxygen (O(2)) in aerated (i.e., water-unsaturated) soils
      affects the metabolic activities of aerobic and anaerobic soil prokaryotes that
      degrade plant-derived saccharides. Fluctuating availabilities of O(2) were
      imposed on agricultural soil slurries supplemented with cellobiose. Slurries were
      subjected to oxic conditions (48 h), followed by an anoxic period (120 h) and a
      final oxic period (24 h). Redox potential was stable at 500 mV during oxic
      periods but decreased rapidly (within 10 h) under anoxic conditions to -330 mV.
      The consumption of cellobiose occurred without apparent delay at all redox
      potentials. The metabolic activities of seven previously identified saccharolytic
      family-level taxa of the investigated soil were measured with newly designed
      quantitative PCR assays targeting the 16S rRNA. Four taxa responded to the
      experimental conditions. The amounts of rRNAs of Micrococcaceae and
      Cellulomonadaceae (Actinobacteria) increased under oxic conditions. In contrast,
      the RNA contents of Clostridiaceae (cluster I, Firmicutes) and two uncultured
      family-level-taxa, i.e., "Cellu" and "Sphingo" (both Bacteroidetes) increased
      under anoxic conditions. That the degradation of cellobiose was independent of
      the availability of O(2) and that redox potentials decreased in response to
      anaerobic activities indicated that the degradation of cellobiose was linked to
      functionally redundant cellobiose-degrading taxa capable of altering redox
      conditions.

PMID- 21742910
TI  - Quantitative analysis of the relative transcript levels of four chlorophenol
      reductive dehalogenase genes in Desulfitobacterium hafniense PCP-1 exposed to
      chlorophenols.
AB  - Relative to those of unexposed cultures, the transcript levels of the four CprA
      type reductive dehalogenase genes (cprA2, cprA3, cprA4, and cprA5) in
      Desulfitobacterium hafniense PCP-1 were measured in cultures exposed to
      chlorophenols. In 2,4,6-trichlorophenol-amended cultures, cprA2 and cprA3 were
      upregulated, as was cprA5, but concomitantly with the appearance of 2,4
      dichlorophenol (DCP). In 3,5-DCP-amended cultures, only cprA5 was upregulated. In
      pentachlorophenol-amended cultures grown for 12 h, cprA2 and cprA3 were
      upregulated but not cprA5. cprA4 was not upregulated significantly in cultures
      containing any tested chlorophenols.

PMID- 21742911
TI  - Novel multiplex single nucleotide polymorphism-based method for identifying
      epidemic clones of Listeria monocytogenes.
AB  - A novel primer extension-based, multiplex minisequencing assay targeting six
      highly informative single nucleotide polymorphisms (SNPs) in four virulence genes
      correctly identified and differentiated all four epidemic clones (ECs) of
      Listeria monocytogenes and 9 other strains initially misclassified as non-ECs.
      This assay allows rapid, accurate, and high-throughput screening for all known
      ECs of L. monocytogenes.

PMID- 21742912
TI  - Persistent phytoplankton bloom in Lake St. Lucia (iSimangaliso Wetland Park,
      South Africa) caused by a cyanobacterium closely associated with the genus
      Cyanothece (Synechococcaceae, Chroococcales).
AB  - Lake St. Lucia, iSimangaliso Wetland Park, South Africa, is the largest estuarine
      lake in Africa. Extensive use and manipulation of the rivers flowing into it have
      reduced freshwater inflow, and the lake has also been subject to a drought of 10
      years. For much of this time, the estuary has been closed to the Indian Ocean,
      and salinities have progressively risen throughout the system, impacting the
      biotic components of the ecosystem, reducing zooplankton and macrobenthic biomass
      and diversity in particular. In June 2009, a bloom of a red/orange planktonic
      microorganism was noted throughout the upper reaches of Lake St. Lucia. The bloom
      persisted for at least 18 months, making it the longest such bloom on record. The
      causative organism was characterized by light and electron microscopy and by 16S
      rRNA sequencing and was shown to be a large, unicellular cyanobacterium most
      strongly associated with the genus Cyanothece. The extent and persistence of the
      bloom appears to be unique to Lake St. Lucia, and it is suggested that the
      organism's resistance to high temperatures, to intense insolation, and to
      hypersalinity as well as the absence of grazing pressure by salinity-sensitive
      zooplankton all contributed to its persistence as a bloom organism until a
      freshwater influx, due to exceptionally heavy summer rains in 2011, reduced the
      salinity for a sufficient length of time to produce a crash in the cyanobacterium
      population as a complex, low-salinity biota redeveloped.

PMID- 21742913
TI  - Total and viable Legionella pneumophila cells in hot and natural waters as
      measured by immunofluorescence-based assays and solid-phase cytometry.
AB  - A new method was developed for the rapid and sensitive detection of viable
      Legionella pneumophila. The method combines specific immunofluorescence (IF)
      staining using monoclonal antibodies with a bacterial viability marker
      (ChemChrome V6 cellular esterase activity marker) by means of solid-phase
      cytometry (SPC). IF methods were applied to the detection and enumeration of both
      the total and viable L. pneumophila cells in water samples. The sensitivity of
      the IF methods coupled to SPC was 34 cells liter(-1), and the reproducibility was
      good, with the coefficient of variation generally falling below 30%. IF methods
      were applied to the enumeration of total and viable L. pneumophila cells in 46
      domestic hot water samples as well as in cooling tower water and natural water
      samples, such as thermal spring water and freshwater samples. Comparison with
      standard plate counts showed that (i) the total direct counts were always higher
      than the plate counts and (ii) the viable counts were higher than or close to the
      plate counts. With domestic hot waters, when the IF assay was combined with the
      viability test, SPC detected up to 3.4 * 10(3) viable but nonculturable L.
      pneumophila cells per liter. These direct IF methods could be a powerful tool for
      high-frequency monitoring of domestic hot waters or for investigating the
      occurrence of viable L. pneumophila in both man-made water systems and
      environmental water samples.

PMID- 21742914
TI  - Anaerobic oxidation of benzene by the hyperthermophilic archaeon Ferroglobus
      placidus.
AB  - Anaerobic benzene oxidation coupled to the reduction of Fe(III) was studied in
      Ferroglobus placidus in order to learn more about how such a stable molecule
      could be metabolized under strict anaerobic conditions. F. placidus conserved
      energy to support growth at 85 degrees C in a medium with benzene provided as the
      sole electron donor and Fe(III) as the sole electron acceptor. The stoichiometry
      of benzene loss and Fe(III) reduction, as well as the conversion of
      [(14)C]benzene to [(14)C]carbon dioxide, was consistent with complete oxidation
      of benzene to carbon dioxide with electron transfer to Fe(III). Benzoate, but not
      phenol or toluene, accumulated at low levels during benzene metabolism, and
      [(14)C]benzoate was produced from [(14)C]benzene. Analysis of gene transcript
      levels revealed increased expression of genes encoding enzymes for anaerobic
      benzoate degradation during growth on benzene versus growth on acetate, but genes
      involved in phenol degradation were not upregulated during growth on benzene. A
      gene for a putative carboxylase that was more highly expressed in benzene- than
      in benzoate-grown cells was identified. These results suggest that benzene is
      carboxylated to benzoate and that phenol is not an important intermediate in the
      benzene metabolism of F. placidus. This is the first demonstration of a
      microorganism in pure culture that can grow on benzene under strict anaerobic
      conditions and for which there is strong evidence for degradation of benzene via
      clearly defined anaerobic metabolic pathways. Thus, F. placidus provides a much
      needed pure culture model for further studies on the anaerobic activation of
      benzene in microorganisms.

PMID- 21742915
TI  - Formation of alkenes via degradation of tert-alkyl ethers and alcohols by
      Aquincola tertiaricarbonis L108 and Methylibium spp.
AB  - Bacterial degradation pathways of fuel oxygenates such as methyl tert-butyl and
      tert-amyl methyl ether (MTBE and TAME, respectively) have already been studied in
      some detail. However, many of the involved enzymes are still unknown, and
      possible side reactions have not yet been considered. In Aquincola
      tertiaricarbonis L108, Methylibium petroleiphilum PM1, and Methylibium sp. strain
      R8, we have now detected volatile hydrocarbons as by-products of the degradation
      of the tert-alkyl ether metabolites tert-butyl and tert-amyl alcohol (TBA and
      TAA, respectively). The alkene isobutene was formed only during TBA catabolism,
      while the beta and gamma isomers of isoamylene were produced only during TAA
      conversion. Both tert-alkyl alcohol degradation and alkene production were
      strictly oxygen dependent. However, the relative contribution of the dehydration
      reaction to total alcohol conversion increased with decreasing oxygen
      concentrations. In resting-cell experiments where the headspace oxygen content
      was adjusted to less than 2%, more than 50% of the TAA was converted to
      isoamylene. Isobutene formation from TBA was about 20-fold lower, reaching up to
      4% alcohol turnover at low oxygen concentrations. It is likely that the putative
      tert-alkyl alcohol monooxygenase MdpJ, belonging to the Rieske nonheme
      mononuclear iron enzymes and found in all three strains tested, or an associated
      enzymatic step catalyzed the unusual elimination reaction. This was also
      supported by the detection of mdpJK genes in MTBE-degrading and isobutene
      emitting enrichment cultures obtained from two treatment ponds operating at
      Leuna, Germany. The possible use of alkene formation as an easy-to-measure
      indicator of aerobic fuel oxygenate biodegradation in contaminated aquifers is
      discussed.

PMID- 21742916
TI  - Mechanism of copper surface toxicity in vancomycin-resistant enterococci
      following wet or dry surface contact.
AB  - Contaminated touch surfaces have been implicated in the spread of hospital
      acquired infections, and the use of biocidal surfaces could help to reduce this
      cross-contamination. In a previous study we reported the death of aqueous inocula
      of pathogenic Enterococcus faecalis or Enterococcus faecium isolates, simulating
      fomite surface contamination, in 1 h on copper alloys, compared to survival for
      months on stainless steel. In our current study we observed an even faster kill
      of over a 6-log reduction of viable enterococci in less than 10 min on copper
      alloys with a "dry" inoculum equivalent to touch contamination. We investigated
      the effect of copper(I) and copper(II) chelation and the quenching of reactive
      oxygen species on cell viability assessed by culture and their effects on genomic
      DNA, membrane potential, and respiration in situ on metal surfaces. We propose
      that copper surface toxicity for enterococci involves the direct or indirect
      action of released copper ionic species and the generation of superoxide,
      resulting in arrested respiration and DNA breakdown as the first stages of cell
      death. The generation of hydroxyl radicals by the Fenton reaction does not appear
      to be the dominant instrument of DNA damage. The bacterial membrane potential is
      unaffected in the early stages of wet and dry surface contact, suggesting that
      the membrane is not compromised until after cell death. These results also
      highlight the importance of correct surface cleaning protocols to perpetuate
      copper ion release and prevent the chelation of ions by contaminants, which could
      reduce the efficacy of the surface.

PMID- 21742917
TI  - Pulsed-field gel electrophoresis and PCR characterization of environmental Vibrio
      parahaemolyticus strains of different origins.
AB  - The present study used pulsed-field gel electrophoresis (PFGE) characterization
      to examine the intraspecies variability and genetic relationships among
      environmental isolates of Vibrio parahaemolyticus from different European
      countries. This is first study performed on environmental V. parahaemolyticus
      that included more than one European country.

PMID- 21742918
TI  - Net production and consumption of fluorescent colored dissolved organic matter by
      natural bacterial assemblages growing on marine phytoplankton exudates.
AB  - An understanding of the distribution of colored dissolved organic matter (CDOM)
      in the oceans and its role in the global carbon cycle requires a better knowledge
      of the colored materials produced and consumed by marine phytoplankton and
      bacteria. In this work, we examined the net uptake and release of CDOM by a
      natural bacterial community growing on DOM derived from four phytoplankton
      species cultured under axenic conditions. Fluorescent humic-like substances
      exuded by phytoplankton (excitation/emission [Ex/Em] wavelength, 310 nm/392 nm;
      Coble's peak M) were utilized by bacteria in different proportions depending on
      the phytoplankton species of origin. Furthermore, bacteria produced humic-like
      substances that fluoresce at an Ex/Em wavelength of 340 nm/440 nm (Coble's peak
      C). Differences were also observed in the Ex/Em wavelengths of the protein-like
      materials (Coble's peak T) produced by phytoplankton and bacteria. The induced
      fluorescent emission of CDOM produced by prokaryotes was an order of magnitude
      higher than that of CDOM produced by eukaryotes. We have also examined the final
      compositions of the bacterial communities growing on the exudates, which differed
      markedly depending on the phytoplankton species of origin. Alteromonas and
      Roseobacter were dominant during all the incubations on Chaetoceros sp. and
      Prorocentrum minimum exudates, respectively. Alteromonas was the dominant group
      growing on Skeletonema costatum exudates during the exponential growth phase, but
      it was replaced by Roseobacter afterwards. On Micromonas pusilla exudates,
      Roseobacter was replaced by Bacteroidetes after the exponential growth phase. Our
      work shows that fluorescence excitation-emission matrices of CDOM can be a
      helpful tool for the identification of microbial sources of DOM in the marine
      environment, but further studies are necessary to explore the association of
      particular bacterial groups with specific fluorophores.

PMID- 21742919
TI  - Ecosystem screening approach for pathogen-associated microorganisms affecting
      host disease.
AB  - The microbial community in which a pathogen evolves is fundamental to disease
      outcome. Species interacting with a pathogen on the host surface shape the
      distribution, density, and genetic diversity of the inoculum, but the role of
      these species is rarely determined. The screening method developed here can be
      used to characterize pathogen-associated species affecting disease. This strategy
      involves three steps: (i) constitution of the microbial community, using the
      pathogen as a trap; (ii) community selection, using extracts from the pathogen as
      the sole nutrient source; and (iii) molecular identification and the screening of
      isolates focusing on their effects on the growth of the pathogen in vitro and
      host disease. This approach was applied to a soilborne plant pathogen,
      Phytophthora parasitica, structured in a biofilm, for screening the microbial
      community from the rhizosphere of Nicotiana tabacum (the host). Two of the
      characterized eukaryotes interfered with the oomycete cycle and may affect the
      host disease. A Vorticella species acted through a mutualistic interaction with
      P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma
      species established an amensal interaction with P. parasitica, strongly
      suppressing disease by inhibiting P. parasitica germination. This screening
      method is appropriate for all nonobligate pathogens. It allows the definition of
      microbial species as promoters or suppressors of a disease for a given biotope.
      It should also help to identify important microbial relationships for ecology and
      evolution of pathogens.

PMID- 21742920
TI  - Repeated anaerobic microbial redox cycling of iron.
AB  - Some nitrate- and Fe(III)-reducing microorganisms are capable of oxidizing Fe(II)
      with nitrate as the electron acceptor. This enzymatic pathway may facilitate the
      development of anaerobic microbial communities that take advantage of the energy
      available during Fe-N redox oscillations. We examined this phenomenon in
      synthetic Fe(III) oxide (nanocrystalline goethite) suspensions inoculated with
      microflora from freshwater river floodplain sediments. Nitrate and acetate were
      added at alternate intervals in order to induce repeated cycles of microbial
      Fe(III) reduction and nitrate-dependent Fe(II) oxidation. Addition of nitrate to
      reduced, acetate-depleted suspensions resulted in rapid Fe(II) oxidation and
      accumulation of ammonium. High-resolution transmission electron microscopic
      analysis of material from Fe redox cycling reactors showed amorphous coatings on
      the goethite nanocrystals that were not observed in reactors operated under
      strictly nitrate- or Fe(III)-reducing conditions. Microbial communities
      associated with N and Fe redox metabolism were assessed using a combination of
      most-probable-number enumerations and 16S rRNA gene analysis. The nitrate
      reducing and Fe(III)-reducing cultures were dominated by denitrifying
      Betaproteobacteria (e.g., Dechloromonas) and Fe(III)-reducing Deltaproteobacteria
      (Geobacter), respectively; these same taxa were dominant in the Fe cycling
      cultures. The combined chemical and microbiological data suggest that both
      Geobacter and various Betaproteobacteria participated in nitrate-dependent Fe(II)
      oxidation in the cycling cultures. Microbially driven Fe-N redox cycling may have
      important consequences for both the fate of N and the abundance and reactivity of
      Fe(III) oxides in sediments.

PMID- 21742921
TI  - Comparison of the host specificities of two bacteroidales quantitative PCR assays
      used for tracking human fecal contamination.
AB  - The sewage-associated real-time quantitative PCR (qPCR) assays BacHum and HF183
      SYBR were compared for specificity against local fecal sources. Both assays were
      equally sensitive to sewage, but BacHum showed substantially more false-positive
      results for cat, dog, gull, and raccoon feces.

PMID- 21742922
TI  - Possible overestimation of surface disinfection efficiency by assessment methods
      based on liquid sampling procedures as demonstrated by in situ quantification of
      spore viability.
AB  - The standard test methods used to assess the efficiency of a disinfectant applied
      to surfaces are often based on counting the microbial survivors sampled in a
      liquid, but total cell removal from surfaces is seldom achieved. One might
      therefore wonder whether evaluations of microbial survivors in liquid-sampled
      cells are representative of the levels of survivors in whole populations. The
      present study was thus designed to determine the "damaged/undamaged" status
      induced by a peracetic acid disinfection for Bacillus atrophaeus spores deposited
      on glass coupons directly on this substrate and to compare it to the status of
      spores collected in liquid by a sampling procedure. The method utilized to assess
      the viability of both surface-associated and liquid-sampled spores included
      fluorescence labeling with a combination of Syto 61 and Chemchrome V6 dyes and
      quantifications by analyzing the images acquired by confocal laser scanning
      microscopy. The principal result of the study was that the viability of spores
      sampled in the liquid was found to be poorer than that of surface-associated
      spores. For example, after 2 min of peracetic acid disinfection, less than 17% +/
      5% of viable cells were detected among liquid-sampled cells compared to 79% +/-
      5% or 47% +/- 4%, respectively, when the viability was evaluated on the surface
      after or without the sampling procedure. Moreover, assessments of the survivors
      collected in the liquid phase, evaluated using the microscopic method and
      standard plate counts, were well correlated. Evaluations based on the
      determination of survivors among the liquid-sampled cells can thus overestimate
      the efficiency of surface disinfection procedures.

PMID- 21742923
TI  - Biochemical characterization and relative expression levels of multiple
      carbohydrate esterases of the xylanolytic rumen bacterium Prevotella ruminicola
      23 grown on an ester-enriched substrate.
AB  - We measured expression and used biochemical characterization of multiple
      carbohydrate esterases by the xylanolytic rumen bacterium Prevotella ruminicola
      23 grown on an ester-enriched substrate to gain insight into the carbohydrate
      esterase activities of this hemicellulolytic rumen bacterium. The P. ruminicola
      23 genome contains 16 genes predicted to encode carbohydrate esterase activity,
      and based on microarray data, four of these were upregulated >2-fold at the
      transcriptional level during growth on an ester-enriched oligosaccharide
      (XOS(FA,Ac)) from corn relative to a nonesterified fraction of corn
      oligosaccharides (AXOS). Four of the 16 esterases (Xyn10D-Fae1A, Axe1-6A, AxeA1,
      and Axe7A), including the two most highly induced esterases (Xyn10D-Fae1A and
      Axe1-6A), were heterologously expressed in Escherichia coli, purified, and
      biochemically characterized. All four enzymes showed the highest activity at
      physiologically relevant pH (6 to 7) and temperature (30 to 40 degrees C) ranges.
      The P. ruminicola 23 Xyn10D-Fae1A (a carbohydrate esterase [CE] family 1 enzyme)
      released ferulic acid from methylferulate, wheat bran, corn fiber, and
      XOS(FA,Ac), a corn fiber-derived substrate enriched in O-acetyl and ferulic acid
      esters, but exhibited negligible activity on sugar acetates. As expected, the P.
      ruminicola Axe1-6A enzyme, which was predicted to possess two distinct esterase
      family domains (CE1 and CE6), released ferulic acid from the same substrates as
      Xyn10D-Fae1 and was also able to cleave O-acetyl ester bonds from various
      acetylated oligosaccharides (AcXOS). The P. ruminicola 23 AxeA1, which is not
      assigned to a CE family, and Axe7A (CE7) were found to be acetyl esterases that
      had activity toward a broad range of mostly nonpolymeric acetylated substrates
      along with AcXOS. All enzymes were inhibited by the proximal location of other
      side groups like 4-O-methylglucuronic acid, ferulic acid, or acetyl groups. The
      unique diversity of carbohydrate esterases in P. ruminicola 23 likely gives it
      the ability to hydrolyze substituents on the xylan backbone and enhances its
      capacity to efficiently degrade hemicellulose.

PMID- 21742924
TI  - Genome data mining and soil survey for the novel group 5 [NiFe]-hydrogenase to
      explore the diversity and ecological importance of presumptive high-affinity H(2)
      oxidizing bacteria.
AB  - Streptomyces soil isolates exhibiting the unique ability to oxidize atmospheric
      H(2) possess genes specifying a putative high-affinity [NiFe]-hydrogenase. This
      study was undertaken to explore the taxonomic diversity and the ecological
      importance of this novel functional group. We propose to designate the genes
      encoding the small and large subunits of the putative high-affinity hydrogenase
      hhyS and hhyL, respectively. Genome data mining revealed that the hhyL gene is
      unevenly distributed in the phyla Actinobacteria, Proteobacteria, Chloroflexi,
      and Acidobacteria. The hhyL gene sequences comprised a phylogenetically distinct
      group, namely, the group 5 [NiFe]-hydrogenase genes. The presumptive high
      affinity H(2)-oxidizing bacteria constituting group 5 were shown to possess a
      hydrogenase gene cluster, including the genes encoding auxiliary and structural
      components of the enzyme and four additional open reading frames (ORFs) of
      unknown function. A soil survey confirmed that both high-affinity H(2) oxidation
      activity and the hhyL gene are ubiquitous. A quantitative PCR assay revealed that
      soil contained 10(6) to 10(8) hhyL gene copies g (dry weight)(-1). Assuming one
      hhyL gene copy per genome, the abundance of presumptive high-affinity H(2)
      oxidizing bacteria was higher than the maximal population size for which
      maintenance energy requirements would be fully supplied through the H(2)
      oxidation activity measured in soil. Our data indicate that the abundance of the
      hhyL gene should not be taken as a reliable proxy for the uptake of atmospheric
      H(2) by soil, because high-affinity H(2) oxidation is a facultatively mixotrophic
      metabolism, and microorganisms harboring a nonfunctional group 5 [NiFe]
      hydrogenase may occur.

PMID- 21742926
TI  - Transcription analysis of a lantibiotic gene cluster from Bifidobacterium longum
      DJO10A.
AB  - Bifidobacterium longum DJO10A was previously demonstrated to produce a
      lantibiotic, but only during growth on agar media. To evaluate the feasibility of
      production of this lantibiotic in broth media, a transcription analysis of the
      lanA gene was undertaken. Comparative microarray analysis of broth and agar
      cultures of B. longum DJO10A revealed that the lantibiotic production,
      modification, transport/peptidase, and immunity genes were significantly
      upregulated in agar cultures, while the two-component regulatory genes were
      expressed equally under both conditions. This suggested that the signal
      transduction regulatory system should function in broth cultures. Real-time PCR
      and Northern hybridization confirmed that lanA gene expression was significantly
      repressed in broth cultures. A crude lantibiotic preparation from an agar-grown
      culture was obtained, and its antimicrobial spectrum analysis revealed a broad
      inhibition range. Addition of this extract to broth cultures of B. longum DJO10A
      induced lanA gene expression in a dose-dependent fashion. Subinoculation using
      >10% of an induced broth culture maintained lanA expression. The expression of
      lanA was log-phase specific, being significantly downregulated in stationary
      phase. Transcription start analysis of lanA revealed a 284-bp 5' untranslated
      region, which was proposed to be involved in repression of transcription, while
      an inverted repeat structure located at bp -75 relative to the transcription
      start was strategically located to likely function as a binding site for the two
      component response regulator. Understanding the transcription regulation of this
      lanA gene is the first step toward enabling production of this novel and
      potentially interesting lantibiotic in broth cultures.

PMID- 21742925
TI  - Identification and characterization of potential performance-related gut
      microbiotas in broiler chickens across various feeding trials.
AB  - Three broiler feeding trials were investigated in order to identify gut bacteria
      consistently linked with improvements in bird performance as measured by feed
      efficiency. Trials were done in various geographic locations and varied in diet
      composition, broiler breed, and bird age. Gut microbial communities were
      investigated using microbial profiling. Eight common performance-linked
      operational taxonomic units (OTUs) were identified within both the ilea (180,
      492, and 564-566) and ceca (140-142, 218-220, 284-286, 312, and 482) across
      trials. OTU 564-566 was associated with lower performance, while OTUs 140-142,
      482, and 492 were associated with improved performance. Targeted cloning and
      sequencing of these eight OTUs revealed that they represented 26 bacterial
      species or phylotypes which clustered phylogenetically into seven groups related
      to Lactobacillus spp., Ruminococcaceae, Clostridiales, Gammaproteobacteria,
      Bacteroidales, Clostridiales/Lachnospiraceae, and unclassified
      bacteria/clostridia. Where bacteria were identifiable to the phylum level, they
      belonged predominantly to the Firmicutes, with Bacteroidetes and Proteobacteria
      also identified. Some of the potential performance-related phylotypes showed high
      sequence identity with classified bacteria (Lactobacillus salivarius,
      Lactobacillus aviarius, Lactobacillus crispatus, Faecalibacterium prausnitzii,
      Escherichia coli, Gallibacterium anatis, Clostridium lactatifermentans,
      Ruminococcus torques, Bacteroides vulgatus, and Alistipes finegoldii). The 16S
      rRNA gene sequence information generated will allow quantitative assays to be
      developed which will enable elucidations of which of these phylotypes are truly
      performance related. This information could be used to monitor strategies to
      improve feed efficiency and feed formulation for optimal gut health.

PMID- 21742927
TI  - Staphylococcus aureus host range and human-bovine host shift.
AB  - Staphylococcus aureus is a major agent of bovine mastitis. The concomitant
      emergence of pig-associated methicillin-resistant S. aureus (MRSA) in human
      carriage and infection requires a reexamination of the host range and specificity
      of human- and cow-associated S. aureus strains, something which has not been
      systematically studied previously. The genetic relatedness of 500 S. aureus
      isolates from bovine mastitis cases, 57 isolates from nasal carriage of farmers,
      and 133 isolates from nonfarmers was determined by amplified fragment length
      polymorphism (AFLP) analysis and spa typing. Multilocus sequence typing (MLST)
      was conducted on a subset of isolates to match AFLP clusters with MLST clonal
      complexes (CCs). This data set allowed us to study host range and host
      specificity and to estimate the extent of bovine-to-human transmission. The
      genotype compositions of S. aureus isolates from farmers and nonfarmers were very
      similar, while the mastitis isolates were quite distinct. Overall, transmission
      was low, but specific genotypes did show increased cow-to-human transmission.
      Unexpectedly, more than one-third of mastitis isolates belonged to CC8, a lineage
      which has not been considered to be bovine mastitis associated, but it is well
      known from human carriage and infection (i.e., USA300). Despite the fact that we
      did detect some transmission of other genotypes from cows to farmers, no
      transmission of CC8 isolates to farmers was detected, except for one tentative
      case. This was despite the close genetic relatedness of mastitis CC8 strains to
      nonfarmer carriage strains. These results suggest that the emergence of the new
      bovine-adapted genotype was due to a recent host shift from humans to cows
      concurrent with a loss of the ability to colonize humans. More broadly, our
      results indicate that host specificity is a lineage-specific trait that can
      rapidly evolve.

PMID- 21742928
TI  - Identification of a toluene-degrading bacterium from a soil sample through
      H(2)(18)O DNA stable isotope probing.
AB  - DNA stable isotope probing (DNA-SIP) with H(2)(18)O was used to identify a
      toluene-degrading bacterium in soil amended with 48 ppm toluene. After
      quantification of toluene degradation rates in soil, DNA was extracted from soil
      incubated with H(2)(18)O, H(2)(16)O, H(2)(16)O and 48 ppm toluene, or H(2)(18)O
      and 48 ppm toluene. A single DNA band formed along a cesium chloride gradient
      after isopycnic centrifugation of extracts from soils incubated with H(2)(16)O.
      With extracts from soils to which only H(2)(18)O was added, two distinct DNA
      bands formed, while three bands formed when DNA extracted from soil incubated
      with both H(2)(18)O and toluene was analyzed. We suggest that this third band
      formed because toluene does not contain any oxygen atoms and toluene-degrading
      organisms had to transfer oxygen atoms from H(2)(18)O into metabolic
      intermediates to form nucleic acids de novo. We extracted the third DNA band and
      amplified a large fraction of the bacterial 16S rRNA gene. Direct sequencing of
      the PCR product obtained from the labeled DNA, as well as cloned 16S rRNA
      amplicons, identified a known toluene degrader, Rhodococcus jostii RHA1. A
      toluene-degrading bacterial strain was subsequently isolated from soil and shown
      to be Rhodococcus jostii RHA1. Finally, quantitative real-time PCR analysis
      showed that the abundance of the 16S rRNA gene of Rhodococcus jostii RHA1
      increased in soil after toluene exposure but not in soils from which toluene was
      withheld. This study indicates that H(2)(18)O DNA-SIP can be a useful method for
      identifying pollutant-degrading bacteria in soil.

PMID- 21742929
TI  - Heavy-machinery traffic impacts methane emissions as well as methanogen abundance
      and community structure in oxic forest soils.
AB  - Temperate forest soils are usually efficient sinks for the greenhouse gas
      methane, at least in the absence of significant amounts of methanogens. We
      demonstrate here that trafficking with heavy harvesting machines caused a large
      reduction in CH(4) consumption and even turned well-aerated forest soils into net
      methane sources. In addition to studying methane fluxes, we investigated the
      responses of methanogens after trafficking in two different forest sites.
      Trafficking generated wheel tracks with different impact (low, moderate, severe,
      and unaffected). We found that machine passes decreased the soils' macropore
      space and lowered hydraulic conductivities in wheel tracks. Severely compacted
      soils yielded high methanogenic abundance, as demonstrated by quantitative PCR
      analyses of methyl coenzyme M reductase (mcrA) genes, whereas these sequences
      were undetectable in unaffected soils. Even after a year after traffic
      compression, methanogen abundance in compacted soils did not decline, indicating
      a stability of methanogens here over time. Compacted wheel tracks exhibited a
      relatively constant community structure, since we found several persisting mcrA
      sequence types continuously present at all sampling times. Phylogenetic analysis
      revealed a rather large methanogen diversity in the compacted soil, and most mcrA
      gene sequences were mostly similar to known sequences from wetlands. The majority
      of mcrA gene sequences belonged either to the order Methanosarcinales or
      Methanomicrobiales, whereas both sites were dominated by members of the families
      Methanomicrobiaceae Fencluster, with similar sequences obtained from peatland
      environments. The results show that compacting wet forest soils by heavy
      machinery causes increases in methane production and release.

PMID- 21742930
TI  - Decrease in the autotrophic-to-heterotrophic biomass ratio of picoplankton in
      oligotrophic marine waters due to bottle enclosure.
AB  - We investigated the effects of bottle enclosure on autotrophic and heterotrophic
      picoplankton in North and South subtropical Atlantic oligotrophic waters, where
      the biomass and metabolism of the microbial community are dominated by the
      picoplankton size class. We measured changes in both autotrophic
      (Prochlorococcus, Synechococcus, and picoeukaryotes) and heterotrophic
      picoplankton biomass during three time series experiments and in 16 endpoint
      experiments over 24 h in light and dark treatments. Our results showed a
      divergent effect of bottle incubation on the autotrophic and heterotrophic
      components of the picoplankton community. The biomass of picophytoplankton
      showed, on average, a >50% decrease, mostly affecting the picoeukaryotes and, to
      a lesser extent, Prochlorococcus. In contrast, the biomass of heterotrophic
      bacteria remained constant or increased during the incubations. We also sampled
      10 stations during a Lagrangian study in the North Atlantic subtropical gyre,
      which enabled us to compare the observed changes in the auto- to heterotrophic
      picoplankton biomass ratio (AB:HB ratio) inside the incubation bottles with those
      taking place in situ. While the AB:HB ratio in situ remained fairly constant
      during the Lagrangian study, it decreased significantly during the 24 h of
      incubation experiments. Thus, the rapid biomass changes observed in the
      incubations are artifacts resulting from bottle confinement and do not take place
      in natural conditions. Our results suggest that short (<1 day) bottle incubations
      in oligotrophic waters may lead to biased estimates of the microbial metabolic
      balance by underestimating primary production and/or overestimating bacterial
      respiration.

PMID- 21742931
TI  - Of blood and death: a test of dual-existential systems in the context of
      prosocial intentions.

PMID- 21742932
TI  - Sticky thoughts: depression and rumination are associated with difficulties
      manipulating emotional material in working memory.
AB  - Cognitive inflexibility may play an important role in rumination, a risk factor
      for the onset and maintenance of depressive episodes. In the study reported here,
      we assessed participants' ability to either reverse or maintain in working memory
      the order of three emotion or three neutral words. Differences (or sorting costs)
      between response latencies in backward trials, on which participants were asked
      to reverse the order of the words, and forward trials, on which participants were
      asked to remember the words in the order in which they were presented, were
      calculated. Compared with control participants, depressed participants had higher
      sorting costs, particularly when presented with negative words. It is important
      to note that rumination predicted sorting costs for negative words but not for
      positive or neutral words in the depressed group. These findings indicate that
      depression and rumination are associated with deficits in cognitive control.

PMID- 21742933
TI  - A single exposure to the American flag shifts support toward Republicanism up to
      8 months later.
AB  - There is scant evidence that incidental cues in the environment significantly
      alter people's political judgments and behavior in a durable way. We report that
      a brief exposure to the American flag led to a shift toward Republican beliefs,
      attitudes, and voting behavior among both Republican and Democratic participants,
      despite their overwhelming belief that exposure to the flag would not influence
      their behavior. In Experiment 1, which was conducted online during the 2008 U.S.
      presidential election, a single exposure to an American flag resulted in a
      significant increase in participants' Republican voting intentions, voting
      behavior, political beliefs, and implicit and explicit attitudes, with some
      effects lasting 8 months after the exposure to the prime. In Experiment 2, we
      replicated the findings more than a year into the current Democratic presidential
      term. These results constitute the first evidence that nonconscious priming
      effects from exposure to a national flag can bias the citizenry toward one
      political party and can have considerable durability.

PMID- 21742934
TI  - Hybrid treatment of an aortic arch aneurysm in a patient with a patent right and
      left internal mammary graft.
AB  - The aim of this report is to describe a known hybrid surgical and endovascular
      technique for aortic arch aneurysm repair in a special setting of a patient with
      previous coronary mammary bypass. We present a case of aortic arch aneurysm in a
      66-year-old man with previous coronary bypass. He underwent a hybrid endovascular
      and surgical repair. All supraaortic vessels were debranched, keeping a
      continuous antegrade blood flow through the left and right internal mammary
      arteries to avoid myocardial ischemia. Endovascular treatment of aortic arch
      aneurysms is associated with less mortality and morbidity as compared with open
      surgery. The hybrid procedure with surgical debranching of the supraaortic
      vessels is the most commonly used method. In cases of previous coronary bypass
      with mammary arteries, care must be taken to maintain constant flow through the
      grafts during debranching.

PMID- 21742935
TI  - Preoperative cardiac assessment in patients undergoing major vascular surgery.
AB  - The aim of this study was to evaluate the effectiveness of a preoperative
      standardized cardiac assessment in patients undergoing major vascular surgery.
      From January 2005 to December 2006, 1446 elective interventions for major
      vascular diseases (carotid stenosis, CS; abdominal aortic aneurysm, AAA;
      peripheral arterial obstructive disease, PAOD) were performed; 1090 out of these
      patients underwent preoperative diagnostic assessment on an outpatient basis.
      Thirty-day results in terms of cardiac mortality and morbidity rates were
      recorded. Patients suffered from a CS in 578 cases (53%), an AAA in 303 cases
      (27.8%) and a PAOD in 209 cases (19.2%). Four hundred thirty-two patients (39.6%)
      underwent further evaluation of cardiac functional capacity with non-invasive
      stress testing. Sixteen patients were successfully treated prior to vascular
      surgery. Thirty-day cardiac mortality and morbidity rates were 0.2% and 3.9%,
      respectively. A positive preoperative non-invasive stress testing did not affect
      30-day cardiac outcomes. In conclusion, the use of an accurate preoperative
      cardiac assessment allowed us to obtain satisfactory perioperative results in
      patients undergoing major vascular surgery. Routine preoperative evaluation with
      non-invasive stress testing did not seem to improve perioperative cardiac
      results.

PMID- 21742936
TI  - Some technical considerations of open thoracoabdominal aortic aneurysm repair in
      a transition country.
AB  - A variety of operative approaches and protective adjuncts have been used in
      thoracoabdominal aneurysm (TAA) repair to minimize the major complications of
      perioperative death and spinal cord ischemia. There is no consensus with respect
      to the optimal approach. We present 118 surgically treated patients over a 10
      year period. The present study reviews our experience as a transition country
      (Serbia) in the treatment and problems we have encountered during open operative
      treatment of TAAs. Between 1999 and 2009, the authors reviewed 118 consecutive
      patients who underwent thoracoabdominal aortic resection using a variety of
      spinal cord protection. Clinical data collected prospectively were analyzed
      retrospectively. The purpose of the current study was to review the results of a
      large series of TAA repairs and to present some technical considerations and
      complications of open TAA repair. There were seven operative deaths (5.9%): two
      in the setting of ruptured TAAs, three myocardial infarctions and two due to
      hemorrhage. All 30 (25.4%) postoperative deaths occurred during the initial
      hospitalization. Postoperative complications included paraplegia in 11 patients
      (9.3%); renal failure in eight patients (6.8%), with four patients (3.4%)
      requiring hemodialysis; pulmonary complications in 75 patients (63.5%); bleeding
      requiring reoperation in two patients (1.7%) and coagulopathic hemorrhage in five
      patients (4.2%); cardiac complications in six patients (5.1%); stroke in five
      patients (4.2%); wound dehiscence in six patients (5.1%); and subdural hemorrhage
      in one patient (0.87%). Open TAA repair intrinsically has substantial
      complications, of which spinal cord ischemia and renal failure are the most
      devastating, despite major progress in our understanding of the pathophysiology
      and operative strategy. Our current review of data clearly proves that the
      surgical repair of TAAs remains a challenge even in the 21st century, especially
      in a country in transition.

PMID- 21742937
TI  - Blunt injury of the innominate artery and left innominate vein.
AB  - Injuries to the branches of the aortic arch are rare and may be caused by blunt,
      penetrating, blast or iatrogenic trauma. Innominate vascular injury is a rare
      entity, particularly in blunt trauma. It is estimated that 71% of patients with
      innominate injuries die before arrival at the hospital. We report here a
      successfully managed case of a combined blunt trauma of the innominate artery and
      transection of the left innominate vein after blunt injury to the chest.

PMID- 21742938
TI  - Clusterin induces matrix metalloproteinase-9 expression via ERK1/2 and
      PI3K/Akt/NF-kappaB pathways in monocytes/macrophages.
AB  - Most solid tumor tissues possess a significant population of macrophages, which
      are known to be closely linked with tumor progression and metastasis. Clusterin
      has been reported to be overexpressed in various tumors and to have a tumor
      promoting role. As clusterin induction and macrophage infiltration occur
      concurrently at the tumor site, it raises a possibility that clusterin may
      regulate the function of macrophages via facilitating ECM remodeling. Here, we
      demonstrate for the first time the expression of MMP-9 by clusterin in human
      primary monocytes as well as human and murine macrophage cell lines, THP-1, and
      Raw264.7. MMP-9 expression was accompanied by increased enzymatic activity, as
      revealed by gelatin zymography. The MMP-9 activity promoted by clusterin was
      found to be dependent on the activation of ERK1/2 and PI3K/Akt but not p38 or JNK
      pathways. Inhibition of PI3K activity did not affect the activation of ERK1/2 and
      vice versa, indicating that the two pathways were independently operated to
      stimulate MMP-9 activity. Moreover, clusterin facilitated nuclear translocation
      of NF-kappaB p65 along with IkappaB-alpha degradation and phosphorylation, which
      was critical for MMP-9 expression. As NF-kappaB is a central regulator of
      inflammation, clusterin may provide a molecular link between inflammation and
      cancer via up-regulating NF-kappaB and MMP-9. Collectively, these data highlight
      a novel role of clusterin as a stimulator for MMP-9 expression in macrophages,
      which may contribute to the tissue reorganization by serving as a modulator for
      ECM degradation.

PMID- 21742939
TI  - Natural killer cell-mediated response to human cytomegalovirus-infected
      macrophages is modulated by their functional polarization.
AB  - MPhi comprise a heterogeneous population of cells, which contribute to host
      defense and maintenance of immune homeostasis. MPhi may be infected by human
      cytomegalovirus (HCMV), which has evolved different strategies to subvert the
      immune response. In the present study, we comparatively analyzed the natural
      killer (NK) cell response against HCMV (TB40E)-infected proinflammatory (M1) and
      antinflammatory (M2) MPhi, derived from autologous monocytes, cultured in the
      presence of GM-CSF and M-CSF, respectively. M1 MPhi were more resistant to
      infection and secreted IL-6, TNF-alpha, IFN-alpha, and IL-12; by contrast, in
      HCMV-infected M2 MPhi, proinflammatory cytokines, IL-10, and IFN-alpha production
      were limited and IL-12 was undetectable. NK cell degranulation was triggered by
      interaction with HCMV-infected M1 and M2 MPhi at 48 h postinfection. The response
      was partially inhibited by specific anti-NKp46, anti-DNAM-1, and anti-2B4 mAb,
      thus supporting a dominant role of these activating receptors. By contrast, only
      HCMV-infected M1 MPhi efficiently promoted NK cell-mediated IFN-gamma secretion,
      an effect partially related to IL-12 production. These observations reveal
      differences in the NK cell response triggered by distinct, HCMV-infected,
      monocyte-derived cell types, which may be relevant in the immunopathology of this
      viral infection.

PMID- 21742940
TI  - Amino acid digestibility in heated soybean meal fed to growing pigs.
AB  - Heat treatment of soybean meal (SBM) is necessary to reduce the concentration of
      trypsin inhibitors, but excessive heat treatment may reduce AA concentration and
      digestibility because AA can be destroyed by the Maillard reaction. The objective
      of this experiment was to determine the effects of heat treatment of SBM on
      apparent ileal digestibility and standardized ileal digestibility (SID) of AA by
      growing pigs. A source of conventional dehulled SBM (48.5% CP) was divided into 4
      batches. One batch was not additionally heated, 1 batch was autoclaved at 125
      degrees C for 15 min, 1 batch was autoclaved at 125 degrees C for 30 min, and 1
      batch was oven-dried at 125 degrees C for 30 min. Four SBM-cornstarch diets were
      formulated, and each of the 4 batches of SBM was used as the sole source of
      dietary AA in 1 diet. A N-free diet was used to estimate basal endogenous losses
      of AA. Ten growing barrows with an initial BW of 25.3 +/- 2.0 kg were
      individually fitted with a T-cannula in the distal ileum. Pigs were allotted to
      treatments in a replicated 5 * 5 balanced Latin square design with 5 diets and 5
      periods. Each period lasted 7 d, and ileal digesta were collected on d 6 and 7 of
      each period. Results of the experiment indicated that the apparent ileal
      digestibility and SID of CP and all AA decreased linearly (P < 0.01) as the time
      of autoclaving increased from 0 to 30 min. The concentration of furosine and the
      color of samples of SBM indicated that autoclaving resulted in a Maillard
      reaction in the SBM. However, oven drying at 125 degrees C for 30 min did not
      change (P > 0.10) the SID of CP and AA in the SBM or the furosine concentration,
      and the color in the oven-dried sample indicated that this sample was not heat
      damaged. In conclusion, the digestibility of all AA in autoclaved SBM is linearly
      reduced as the autoclaving time increases from 0 to 30 min. The reason for these
      changes is most likely that autoclaving at 125 degrees C results in Maillard
      reactions in SBM.

PMID- 21742941
TI  - Accuracy of genome-wide evaluation for disease resistance in aquaculture breeding
      programs.
AB  - Current aquaculture breeding programs aimed at improving resistance to diseases
      are based on challenge tests, where performance is recorded on sibs of candidates
      to selection, and on selection between families. Genome-wide evaluation (GWE) of
      breeding values offers new opportunities for using variation within families when
      dealing with such traits. However, up-to-date studies on GWE in aquaculture
      programs have only considered continuous traits. The objectives of this study
      were to extend GWE methodology, in particular the Bayes B method, to analyze
      dichotomous traits such as resistance to disease, and to quantify, through
      computer simulation, the accuracy of GWE for disease resistance in aquaculture
      sib-based programs, using the methodology developed. Two heritabilities (0.1 and
      0.3) and 2 disease prevalences (0.1 and 0.5) were assumed in the simulations. We
      followed the threshold liability model, which assumes that there is an underlying
      variable (liability) with a continuous distribution and assumed a BayesB model
      for the liabilities. It was shown that the threshold liability model used fits
      very well with the BayesB model of GWE. The advantage of using the threshold
      model was clear when dealing with disease resistance dichotomous phenotypes,
      particularly under the conditions where linear models are less appropriate (low
      heritability and disease prevalence). In the testing set (where individuals are
      genotyped but not measured), the increase in accuracy for the simulated schemes
      when using the threshold model ranged from 4 (for heritability equal to 0.3 and
      prevalence equal to 0.5) to 16% (for heritability and prevalence equal to 0.1)
      when compared with the linear model.

PMID- 21742942
TI  - Effects of heat stress on proliferation, protein turnover, and abundance of heat
      shock protein messenger ribonucleic acid in cultured porcine muscle satellite
      cells.
AB  - It is well established that heat stress (HS) negatively affects growth rate in
      swine. Although reduced feed intake undoubtedly plays a significant role in this
      reduction, studies in laboratory animals and other nonswine species indicate
      muscle growth also is affected by HS-related alterations in muscle physiology.
      Evidence is now emerging that heat shock proteins (Hsp), produced in response to
      HS and other types of cellular stress, may play an important role in regulating
      the rate and efficiency of muscle growth. Because muscle satellite cells play a
      crucial role in postnatal muscle growth, the effects of HS on rates of satellite
      cell proliferation, protein synthesis, and protein degradation play an important
      role in determining the rate and extent of muscle growth. Consequently, in the
      current study we have examined the effects of mild HS (40.5 degrees C for 48 h)
      on the rates of proliferation, protein synthesis, and protein degradation and on
      quantities of Hsp90, Hsp70, and Hsp25/27 mRNA and protein in cultured porcine
      muscle satellite cells (PSC). Mild HS of PSC cultures resulted in 2.5-, 1.4-, and
      6.5-fold increases (P < 0.05) in the abundance of Hsp90, Hsp70, and Hsp25/27
      mRNA, respectively, relative to control cultures. Abundance of Hsp 90, 70, and
      25/27 proteins was also increased in HS PSC cultures compared with those in
      control cultures. Proliferation rates in HS PSC cultures were 35% less (P < 0.05)
      than those in control cultures. Protein synthesis rates in HS-fused PSC cultures
      were 85% greater (P < 0.05) than those in control cultures, and protein
      degradation rates in HS-fused PSC were 23% less (P < 0.05) than those in control
      cultures. In light of the crucial role satellite cells play in postnatal muscle
      growth, the HS-induced changes we have observed in rates of proliferation,
      protein turnover, and abundance of Hsp mRNA and Hsp protein in PSC cultures
      indicate that mild HS affects the physiology of PSC in ways that could affect
      muscle growth in swine.

PMID- 21742943
TI  - Thermogenesis, blood metabolites and hormones, and growth of lambs born to ewes
      supplemented with algae-derived docosahexaenoic acid.
AB  - Neonatal lamb mortality is a major factor affecting profitability in the sheep
      industry, and lamb thermogenesis is a key element in neonatal lamb survival.
      Increased lamb vigor has been reported when ewes were supplemented during late
      gestation with algae-derived docosahexaenoic acid (DHA); however, the effects of
      DHA on lamb thermogenesis and immunocompetence have not been investigated. Eighty
      twin-bearing Targhee ewes (ages 2 to 5 yr; 68.5 +/- 3 kg) were assigned randomly
      to 1 of 2 supplement treatments to determine the effects of feeding DHA to ewes
      during late gestation and early lactation on lamb thermogenesis, serum
      metabolites and hormones, and lamb growth. Supplement treatments were 12 g.ewe(
      1).d(-1) of algae-derived DHA (DHA Gold Advanced Bionutrition Corp., Columbia,
      MD; algae-derived DHA); and no algae-derived DHA (control). Supplements were
      individually fed daily during the last 30 d (+/-7 d) of gestation and pen fed (6
      pens/treatment with 6 or 7 ewes/pen) during the first 38 d (+/-7 d) of lactation.
      One hour after lambing and before nursing, twin-born lambs were weighed, blood
      sampled via jugular puncture, and placed in a dry cold chamber for 30 min (0
      degrees C), and rectal temperatures were recorded every minute for 30 min. Lambs
      were removed from the cold chamber, blood sampled, warmed for 15 min, and
      returned to their dam. Ewes were blood sampled, and colostrum samples were
      collected 1 h postpartum. Ewe and lamb sera were assayed for glucose, NEFA,
      cortisol, and leptin. Lamb rectal temperature, glucose, NEFA, cortisol, leptin,
      and birth weights did not differ between treatments. The BW at 38 d was greater
      (P = 0.03) for lambs born to control ewes than for lambs born to algae-derived
      DHA-supplemented ewes; however, the colostrum of algae-derived DHA-supplemented
      ewes had a greater specific gravity (P = 0.05) than for control ewes. Overall,
      despite a potentially positive effect on ewe colostral IgG concentrations,
      supplementation of algae-derived DHA during late gestation and early lactation
      had a negative effect on lamb BW and did not affect indices of lamb
      thermogenesis.

PMID- 21742944
TI  - Effects of vitamin E on color stability and palatability of strip loin steaks
      from cattle fed distillers grains.
AB  - The objective of this study was to determine the effect of preslaughter
      antioxidant supplementation to cattle fed wet distillers grains on carcass yield
      and quality grade, and on the color stability and consumer acceptability of
      steaks. Two hundred five crossbred steers were fed 35% wet distillers grains with
      the supplementation of 4 different levels of alpha-tocopheryl acetate: 0, 125,
      250, and 500 IU*animal(-1)*d(-1) for 97 d. Chuck rolls (n = 69) and strip loins
      (n = 185) were collected and processed at 4 and 7 d postslaughter, respectively.
      Chucks were ground and separated into 0.23-kg samples. Strip loins were faced and
      cut into 2.54-cm steaks and packaged in a polyvinyl chloride overwrapped (PVC)
      package, a vacuum package, or modified atmosphere packages (MAP) for further
      color, alpha-tocopherol, objective tenderness, palatability, and proximate
      analysis. Color was measured objectively using a HunterLab Miniscan XE
      spectrophotometer (HunterLab Associates Inc., Reston, VA) and subjectively by a
      trained color panel, and a consumer panel was used to indicate which treatments
      affected retail acceptability and purchase decisions. Warner-Bratzler shear force
      measurements were used for objective tenderness, and a trained panel assessed
      subjective palatability characteristics. Instrumental color measurements revealed
      little difference for ground beef in both PVC and MAP packages, but diets with
      500 and 250 IU*animal(-1)*d(-1) of vitamin E had a longer (P < 0.05) retention of
      redness and yellowness in steaks as compared with steaks from animals receiving
      less vitamin E. Subjective color evaluation for strip steaks indicated that
      greater vitamin E was more likely (P < 0.05) to maintain color stability, overall
      acceptability, and consumer purchase preference while decreasing percentage of
      discoloration. No significant differences (P > 0.10) were observed for objective
      tenderness and sensory attributes of strip steaks, and no differences (P > 0.10)
      were observed in protein, fat, and moisture percentages of ground beef. Lipid
      oxidation analysis indicated that steaks packaged in PVC for 7 d and MAP for 1,
      3, and 7 d, and ground beef packaged in MAP and PVC for 0 and 7 d of retail
      display required greater inclusion of vitamin E (500 and 250 IU*animal(-1)*d(-1))
      to remain below the 2.28 mg of malonaldehyde/kg threshold. Ultimately, 500
      IU*animal(-1)*d(-1) of vitamin E should be supplemented to cattle fed wet
      distillers grain-based diets when products are packaged in MAP to maximize retail
      shelf life.

PMID- 21742945
TI  - Inverse association of eosinophil count with colorectal cancer incidence:
      atherosclerosis risk in communities study.
AB  - BACKGROUND: Allergic conditions are associated with reduced risk of several
      malignancies. We hypothesized that blood eosinophil count, a marker for allergic
      disorders, is inversely associated with the risk of colorectal cancer (CRC) in
      the Atherosclerosis Risk in Communities prospective cohort. To our knowledge, the
      association between blood eosinophil count and cancer risk has not been
      investigated before. METHODS: Relative eosinophil and total leukocyte counts were
      measured in blood at baseline. Absolute eosinophil counts were calculated by
      multiplying relative count by the total leukocyte count. Proportional hazards
      regression provided HRs and 95% CIs of CRC in relation to eosinophil count.
      RESULTS: From 1987-2006, 242 incident CRC cases (187 colon and 56 rectal)
      occurred in 10,675 initially cancer-free participants. In a multivariate-adjusted
      model, HRs were 1.0, 0.70 (95% CI: 0.50-0.98) and 0.58 (95% CI: 0.40-0.83) across
      tertiles of absolute eosinophil count (P(trend) = 0.003). A similar inverse
      association was observed for relative eosinophil count. Age, sex, race, or
      smoking status did not modify associations. CONCLUSIONS AND IMPACT: We observed
      an inverse association between blood eosinophil count and CRC risk. This novel
      finding supports the hypothesis that allergies are protective for CRC, as an
      increased eosinophil count correlates with allergy in the developed world.

PMID- 21742946
TI  - Estrogen levels in nipple aspirate fluid and serum during a randomized soy trial.
AB  - BACKGROUND: On the basis of hypothesized protective effect, we examined the
      effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum,
      possible indicators of breast cancer risk. METHODS: In a crossover design, we
      randomized 96 women who produced 10 MUL or more NAF to a high- or low-soy diet
      for 6 months. During the high-soy diet, participants consumed 2 soy servings of
      soy milk, tofu, or soy nuts (~50 mg of isoflavones per day); during the low-soy
      diet, they maintained their usual diet. Six NAF samples were obtained using a
      FirstCyte aspirator. Estradiol (E(2)) and estrone sulfate (E(1)S) were assessed
      in NAF and estrone (E(1)) in serum only, using highly sensitive
      radioimmunoassays. Mixed-effects regression models accounting for repeated
      measures and left-censoring limits were applied. RESULTS: Mean E(2) and E(1)S
      were lower during the high-soy than the low-soy diet (113 vs. 313 pg/mL and 46
      vs. 68 ng/mL, respectively) without reaching significance (P = 0.07); the
      interaction between group and diet was not significant. There was no effect of
      the soy treatment on serum levels of E(2) (P = 0.76), E(1) (P = 0.86), or E(1)S
      (P = 0.56). Within individuals, NAF and serum levels of E(2) (r(s) = 0.37; P <
      0.001) but not of E(1)S (r(s) = 0.004; P = 0.97) were correlated. E(2) and E(1)S
      in NAF and serum were strongly associated (r(s) = 0.78 and r(s) = 0.48; P <
      0.001). CONCLUSION: Soy foods in amounts consumed by Asians did not significantly
      modify estrogen levels in NAF and serum. IMPACT: The trend toward lower estrogen
      levels in NAF during the high-soy diet counters concerns about adverse effects of
      soy foods on breast cancer risk.

PMID- 21742947
TI  - Our environment, our health: a community-based participatory environmental health
      survey in Richmond, California.
AB  - This study presents a health survey conducted by a community-based participatory
      research partnership between academic researchers and community organizers to
      consider environmental health and environmental justice issues in four
      neighborhoods of Richmond, California, a low-income community of color living
      along the fence line of a major oil refinery and near other industrial and mobile
      sources of pollution. The Richmond health survey aimed to assess local concerns
      and perceptions of neighborhood conditions, health problems, mobile and
      stationary hazards, access to health care, and other issues affecting residents
      of Richmond. Although respondents thought their neighborhoods were good places to
      live, they expressed concerns about neighborhood stressors and particular sources
      of pollution, and identified elevated asthma rates for children and long-time
      Richmond residents. The Richmond health survey offers a holistic, community
      centered perspective to understanding local environmental health issues, and can
      inform future environmental health research and organizing efforts for community
      university collaboratives.

PMID- 21742948
TI  - Health literacy and women's health-related behaviors in Taiwan.
AB  - Extant health literacy research is unclear about the contribution of health
      literacy to health behaviors and is limited regarding women's health issues. The
      primary purpose of this study is to investigate the association between health
      literacy and five health behaviors (Pap smear screening, annual physical checkup,
      smoking, checking food expiration dates, and monitoring physical changes) in
      women and to test whether the association is mediated by health knowledge. A
      national sample of 1,754 female adults in Taiwan was included in the study.
      Result showed that health literacy was positively and independently related to
      checking food expiration dates and monitoring physical changes, and that health
      literacy was not related to physical checkup and Pap smear screening.
      Interestingly, women with high health literacy were more likely to be a current
      smoker. Study findings suggest that efforts to improve health promotion behaviors
      in women should consider health literacy as an important factor and that the
      effect of health literacy on health prevention behaviors may vary by women's
      access to care.

PMID- 21742949
TI  - Psychotherapy with immigrant patients in France: an ethnopsychiatric perspective.
AB  - This article focuses on recent developments in clinical ethnopsychiatry theorized
      by the French psychologist Tobie Nathan, as understood and practised by a member
      of his clinical research team. Alongside Western psychological theories, Nathan's
      approach sets out to include, within its clinical research setting, cultural and
      religious theories and healing practices related to unhappiness and disease. All
      such theories, regardless of the culture or civilization they belong to, are
      regarded as potentially valid and also as possible therapeutic tools. In this
      perspective, Nathan criticizes the concepts of representation or belief and
      prefers to talk about objects and theories. To illustrate his unique approach to
      therapy, the treatment of a Cameroon immigrant teenager and her family, conducted
      at the University clinic founded by Nathan, is extensively presented in this
      article.

PMID- 21742950
TI  - Current developments in French ethnopsychoanalysis.
AB  - French ethnopsychoanalytic approaches to therapy with immigrants combine the
      psychoanalytical interest in subjectivity with a specific concern for cultural
      factors and with the role migration plays as a crucial life event. Recent
      approaches consider culture as profoundly hybrid and use the notions of
      ''metissage'' and ''decentrage'' as central concepts. This article presents
      extracts from a qualitative study of ethnopsychoanalytic therapies with immigrant
      families. The authors argue that the ethnopsychoanalytic approach helps to open
      new ways of considering cultural hybridity and create a third space where
      experiences ''from the margins'' may be verbalized.

PMID- 21742951
TI  - Translating Fanon in the Italian context: rethinking the ethics of treatment in
      psychiatry.
AB  - Based on two years of ethnographic fieldwork at the Centro Frantz Fanon, an
      ethnopsychiatric clinic in Northern Italy, this article traces the theoretical
      and clinical genealogy of Italian ethnopsychiatry as it is conceived and
      practiced at this clinic. The clinic draws explicitly from the work of Fanon and
      French ethnopsychologist Tobie Nathan. This genealogy provides a basis for
      reflection on the ways in which current ethnopsychiatry re-articulates older
      questions about difference and healing, culture and suffering, and the political
      dimensions of psychiatry. Although ethnopsychiatry is currently focused on the
      care of migrants, key issues related to the impact of colonialism on mental
      illness and the recognition of cultural difference characterized the Italian
      debate long before the 1980s when increasing numbers of migrants and political
      refugees started to arrive in Italy.

PMID- 21742952
TI  - Cultural epidemiology of neurasthenia spectrum disorders in four general hospital
      outpatient clinics of urban Pune, India.
AB  - Disorders emphasizing symptoms of fatigue and/or weakness, collectively termed
      Neurasthenia Spectrum Disorders (NSDs), typically emphasize a biological basis in
      the West and social origins in East Asia. In India, explanatory concepts are
      diverse. To clarify, 352 outpatients in Psychiatry, Medicine, Dermatology, and
      Ayurved clinics of an urban hospital were interviewed with a version of the
      Explanatory Model Interview Catalogue. Comparisons of categories and narratives
      of illness experience and meaning across clinics indicated both shared and
      distinctive features. Explanatory models of NSDs highlighted social distress,
      ''tensions,'' and both general and clinic-specific physical, psychological, and
      cultural ideas. Findings indicate the importance of social contexts and cultural
      meaning in explanatory models of neurasthenia, as well as the potential clinical
      relevance of the construct of Neurasthenia Spectrum Disorder.

PMID- 21742953
TI  - Cooperation and contention in psychiatric work.
AB  - This article discusses the social organization of psychiatric work in the
      psychiatric emergency department of a public general hospital located in New York
      City, based on ethnographic research conducted from 1999 to 2001. Case studies of
      the care of two patients with ambiguous symptoms are discussed. The analysis
      applies the ''differences approach'' developed by Mol and colleagues which
      focuses on the way different professions provide divergent explanations and
      ontologies for symptoms and illness. The cases illustrate the ways in which
      social structural constraints are compelling psychiatry to become a
      multidisciplinary specialty.

PMID- 21742954
TI  - Self-immolation, suicide and self-harm in Buddhist and Western traditions.
AB  - There are significant points of similarity between considerations of self-harm
      and suicide in Buddhist and non-Buddhist traditions, including qualified
      acceptance of certain forms of self-harm, altruism as a motivation for suicide,
      and self-immolation as a form of political protest. Differences include specific
      contexts in which certain forms of self-harm are accepted and the predominant
      frameworks used to interpret such acts. The integration of Buddhist concepts of
      dukkha (unsatisfactoriness or suffering) and sati (mindfulness) into Western
      psychotherapeutic paradigms represents a significant point of convergence between
      the two traditions, and suggests the possibility of greater dialogue and
      therapeutic benefit in the future.

PMID- 21742955
TI  - Religion and psychosis: a common evolutionary trajectory?
AB  - In this article we propose that schizophrenia and religious cognition engage
      cognate mental modules in the over-attribution of agency and the overextension of
      theory of mind. We argue similarities and differences between assumptions of
      ultrahuman agents with omniscient minds and certain ''pathological'' forms of
      thinking in schizophrenia: thought insertion, withdrawal and broadcasting, and
      delusions of reference. In everyday religious cognition agency detection and
      theory of mind modules function ''normally,'' whereas in schizophrenia both
      modules are impaired. It is suggested that religion and schizophrenia have
      perhaps had a related evolutionary trajectory.

PMID- 21742956
TI  - Leprechauns and Lewy body disease.

PMID- 21742957
TI  - Some corrective notes regarding recent priority setting in Sweden.

PMID- 21742961
TI  - Partial hue-matching.
AB  - It is widely believed that color can be decomposed into a small number of
      component colors. Particularly, each hue can be described as a combination of a
      restricted set of component hues. Methods, such as color naming and hue scaling,
      aim at describing color in terms of the relative amount of the component hues.
      However, there is no consensus on the nomenclature of component hues. Moreover,
      the very notion of hue (not to mention component hue) is usually defined verbally
      rather than perceptually. In this paper, we make an attempt to operationalize
      such a fundamental attribute of color as hue without the use of verbal terms.
      Specifically, we put forth a new method--partial hue-matching--that is based on
      judgments of whether two colors have some hue in common. It allows a set of
      component hues to be established objectively, without resorting to verbal
      definitions. Specifically, the largest sets of color stimuli, all of which
      partially match each other (referred to as chromaticity classes), can be derived
      from the observer's partial hue-matches. A chromaticity class proves to consist
      of all color stimuli that contain a particular component hue. Thus, the
      chromaticity classes fully define the set of component hues. Using samples of
      Munsell papers, a few experiments on partial hue-matching were carried out with
      twelve inexperienced normal trichromatic observers. The results reinforce the
      classical notion of four component hues (yellow, blue, red, and green). Black and
      white (but not gray) were also found to be component colors.

PMID- 21742962
TI  - High-level face shape adaptation depends on visual awareness: evidence from
      continuous flash suppression.
AB  - When incompatible images are presented to the two eyes, one image dominates
      awareness while the other is rendered invisible by interocular suppression. It
      has remained unclear whether complex visual information can reach high-level
      processing stages in the ventral visual pathway during such interocular
      suppression. Here, we asked whether basic face shape, which is thought to be
      encoded in areas of the ventral stream, can be processed without visual
      awareness. We measured aftereffects induced by prolonged exposure to distorted
      faces during continuous flash suppression. Despite constant physical stimulation,
      in some trials the adaptor face was fully suppressed from awareness, while in
      other trials it overcame suppression and became partially visible. Aftereffects
      were induced even by entirely invisible adaptors, albeit reduced compared to
      partially visible adaptors, and only when adaptor and test stimuli were presented
      in the same size to the same eye. However, when adaptor and test stimuli were
      presented to different eyes or to the same eye but in different sizes,
      aftereffects were restricted to partially visible adaptors. These results suggest
      that a monocular, low-level component of face shape adaptation escapes
      interocular suppression and can proceed without visual awareness. By contrast,
      high-level components of basic face shape encoding involving ventral stream
      processing are eliminated by interocular suppression and require visual
      awareness.

PMID- 21742963
TI  - Cardiovascular toxicity profiles of vascular-disrupting agents.
AB  - BACKGROUND: Vascular-disrupting agents (VDAs) represent a new class of
      chemotherapeutic agent that targets the existing vasculature in solid tumors.
      Preclinical and early-phase trials have demonstrated the promising therapeutic
      benefits of VDAs but have also uncovered a distinctive toxicity profile
      highlighted by cardiovascular events. METHODS: We reviewed all preclinical and
      prospective phase I-III clinical trials published up to August 2010 in MEDLINE
      and the American Association of Cancer Research and American Society of Clinical
      Oncology meeting abstracts of small-molecule VDAs, including combretastatin A4
      phosphate (CA4P), combretastatin A1 phosphate (CA1P), MPC-6827, ZD6126, AVE8062,
      and ASA404. RESULTS: Phase I and II studies of CA1P, ASA404, MPC-6827, and CA4P
      all reported cardiovascular toxicities, with the most common cardiac events being
      National Cancer Institute Common Toxicity Criteria (version 3) grade 1-3
      hypertension, tachyarrhythmias and bradyarrhythmias, atrial fibrillation, and
      myocardial infarction. Cardiac events were dose-limiting toxicities in phase I
      trials with VDA monotherapy and combination therapy. CONCLUSIONS: Early-phase
      trials of VDAs have revealed a cardiovascular toxicity profile similar to that of
      their vascular-targeting counterparts, the angiogenesis inhibitors. As these
      agents are added to the mainstream chemotherapeutic arsenal, careful
      identification of baseline cardiovascular risk factors would seem to be a prudent
      strategy. Close collaboration with cardiology colleagues for early indicators of
      serious cardiac adverse events will likely minimize toxicity while optimizing the
      therapeutic potential of VDAs and ultimately enhancing patient outcomes.

PMID- 21742964
TI  - Concordance of predictive markers for EGFR inhibitors in primary tumors and
      metastases in colorectal cancer: a review.
AB  - BACKGROUND: Currently, only Kirsten rat sarcoma 2 viral oncogene homolog (KRAS)
      mutational status is used as a decisional marker for epidermal growth factor
      receptor (EGFR) inhibitor therapy in colorectal cancer (CRC) patients.
      Concordance of KRAS status between primary tumors and metastases has always been
      considered to be close to perfect; however, cases of discordance have been
      reported. The actual rate of concordance of KRAS status remains unclear, as is
      the same for v-raf murine sarcoma viral oncogene homolog B1 (BRAF),
      phosphatidylinositol 3-kinase CA subunit (PIK3CA), and loss of phosphatase and
      tensin homologue deleted on chromosome ten (PTEN). Therefore, it is unknown
      whether it is necessary to perform mutational analysis on metastases instead of
      on (or in addition to) primary tumors. DESIGN: A systematic literature search was
      conducted to collect all studies testing concordance of KRAS in CRC, and also of
      BRAF, PIK3CA, and loss of PTEN. RESULTS: Twenty-one studies have reported
      concordance of KRAS, with an overall concordance rate of 93% (range, 76%-100%).
      Overall concordance rates of studies testing concordance of BRAF status and loss
      of PTEN were 98% and 68%, respectively. Three studies reported concordance of
      PIK3CA status (range, 89%-94%). CONCLUSION: Though discordance of KRAS status
      does occur, it is uncommon. When considering the downsides of testing metastatic
      tissue in all patients along with the low incidence of discordance, we conclude
      that that testing the primary tumor (or whatever tissue available) is sufficient
      for clinical decision making on EGFR inhibitor therapy.

PMID- 21742965
TI  - Reactive carbonyls are a major Th2-inducing damage-associated molecular pattern
      generated by oxidative stress.
AB  - Oxidative stress is widespread and entwined with pathological processes, yet its
      linkage to adaptive immunity remains elusive. Reactive carbonyl (RC) adduction, a
      common feature of oxidative stress, has been shown to target proteins to the
      adaptive immune system. Because aldehydes are important mediators of
      carbonylation, we explored the immunomodulatory properties of model Ags modified
      by common bioactive aldehyde by-products of oxidative stress: 4-hydroxy-2
      nonenal, malondialdehyde, and glycolaldehyde. Ag modification with all three
      aldehydes resulted in Ag-specific IgG1-dominated responses in adjuvant-free
      murine immunizations in an RC-dependent manner. The central role of RCs was
      confirmed, as their reduction into nonreactive groups abrogated all adaptive
      responses, despite the presence of other well-known aldehyde-driven adducts such
      as N(epsilon)-carboxymethyllysine and glycolaldehyde-pyridine. Moreover, Ag
      specific Ab responses robustly correlated with the extent of RC adduction,
      regardless of the means of their generation. T cell responses mirrored the Th2
      biased Ab isotypes by Ag-specific splenocyte production of IL-4, IL-5, and IL-13,
      but not IFN-gamma. The RC-induced Th2 response was in sharp contrast to that
      induced by Th1/Th2 balanced or Th1-biasing adjuvants and was maintained in a
      range of mouse strains. In vitro studies revealed that RC adduction enhanced Ag
      presentation with Th2 polarization in the absence of conventional dendritic cell
      activation. Taken together, these data implicate commonly occurring RC as an
      important oxidation-derived Th2 immunomodulatory damage-associated molecular
      pattern with potentially important roles in health and disease.

PMID- 21742966
TI  - Innate immune responses in human monocyte-derived dendritic cells are highly
      dependent on the size and the 5' phosphorylation of RNA molecules.
AB  - Recognition of viral genetic material takes place via several different receptor
      systems, such as retinoic acid-inducible gene I-like receptors and TLRs 3, 7, 8,
      and 9. At present, systematic comparison of the ability of different types of
      RNAs to induce innate immune responses in human immune cells has been limited. In
      this study, we generated bacteriophage 6 and influenza A virus-specific ssRNA and
      dsRNA molecules ranging from 58 to 2956 nt. In human monocyte-derived dendritic
      cells (moDCs), short dsRNAs efficiently upregulated the expression of IFN (IFN
      alpha, IFN-beta, and IFN-lambda1) and proinflammatory (TNF-alpha, IL-6, IL-12,
      and CXCL10) cytokine genes. These genes were also induced by ssRNA molecules, but
      size-specific differences were not as pronounced as with dsRNA molecules.
      Dephosphorylation of short ssRNA and dsRNA molecules led to a dramatic reduction
      in their ability to stimulate innate immune responses. Such a difference was not
      detected for long ssRNAs. RNA-induced cytokine responses correlated well with IFN
      regulatory factor 3 phosphorylation, suggesting that IFN regulatory factor 3
      plays a major role in both ssRNA- and dsRNA-activated responses in human moDCs.
      We also found that IFN gene expression was efficiently stimulated following
      recognition of short dsRNAs by retinoic acid-inducible gene I and TLR3 in human
      embryonic kidney 293 cells, whereas ssRNA-induced responses were less dependent
      on the size of the RNA molecule. Our data suggest that human moDCs are extremely
      sensitive in recognizing foreign RNA, and the responses depend on RNA size, form
      (ssRNA versus dsRNA), and the level of 5' phosphorylation.

PMID- 21742967
TI  - Soluble proteins induce strong CD8+ T cell and antibody responses through
      electrostatic association with simple cationic or anionic lipopeptides that
      target TLR2.
AB  - The low immunogenicity exhibited by most soluble proteins is generally due to the
      absence of molecular signatures that are recognized by the immune system as
      dangerous. In this study, we show that electrostatic binding of synthetic
      branched cationic or anionic lipopeptides that contain the TLR-2 agonist
      Pam(2)Cys markedly enhance a protein's immunogenicity. Binding of a charged
      lipopeptide to oppositely charged protein Ags resulted in the formation of stable
      complexes and occurs at physiologic pH and salt concentrations. The induction of
      cell-mediated responses is dependent on the electrostatic binding of lipopeptide
      to the protein, with no CD8(+) T cells being elicited when protein and
      lipopeptide possessed the same electrical charge. The CD8(+) T cells elicited
      after vaccination with lipopeptide-protein Ag complexes produced proinflammatory
      cytokines, exhibited in vivo lytic activity, and protected mice from challenge
      with an infectious chimeric influenza virus containing a single OVA epitope as
      part of the influenza neuraminidase protein. Induction of a CD8(+) T cell
      response correlated with the ability of lipopeptide to facilitate Ag uptake by
      DCs followed by trafficking of Ag-bearing cells into draining lymph nodes.
      Oppositely charged but not similarly charged lipopeptides were more effective in
      DC uptake and trafficking. Very high protein-specific Ab titers were also
      achieved by vaccination with complexes composed of oppositely charged lipopeptide
      and protein, whereas vaccination with similarly charged constituents resulted in
      significant but lower Ab titers. Regardless of whether similarly or oppositely
      charged lipopeptides were used in the induction of Ab, vaccination generated
      dominant IgG1 isotype Abs rather than IgG2a.

PMID- 21742968
TI  - Defects in the Bcl-2-regulated apoptotic pathway lead to preferential increase of
      CD25 low Foxp3+ anergic CD4+ T cells.
AB  - Defects in the Bcl-2-regulated apoptotic pathway inhibit the deletion of self
      reactive T cells. What is unresolved, however, is the nature and fate of such
      self-reactive T cells escaping deletion. In this study, we report that mice with
      such defects contained increased numbers of CD25(low)Foxp3(+) cells in the thymus
      and peripheral lymph tissues. The increased CD25(low)Foxp3(+) population
      contained a large fraction of cells bearing self-reactive TCRs, evident from a
      prominent increase in self-superantigen-specific Foxp3(+)Vbeta5(+)CD4(+) T cells
      in BALB/c Bim(-/-) mice compared with control animals. The survival rate of the
      expanded CD25(low)Foxp3(+) cells was similar to that of CD25(high)Foxp3(+) CD4 T
      cells in vitro and in vivo. IL-2R stimulation, but not TCR ligation, upregulated
      CD25 on CD25(low)Foxp3(+)CD4(+) T cells in vitro and in vivo. The expanded
      CD25(low)Foxp3(+)CD4(+) T cells from Bim(-/-) mice were anergic but also had
      weaker regulatory function than CD25(high)Foxp3(+) CD4(+) T cells from the same
      mice. Analysis of Bim(-/-) mice that also lacked Fas showed that the peripheral
      homeostasis of this expanded population was in part regulated by this death
      receptor. In conclusion, these results show that self-reactive T cell escapes
      from thymic deletion in mice defective in the Bcl-2-regulated apoptotic pathway
      upregulate Foxp3 and become unresponsive upon encountering self-Ag without
      necessarily gaining potent regulatory function. This clonal functional diversion
      may help to curtail autoaggressiveness of escaped self-reactive CD4(+) T cells
      and thereby safeguard immunological tolerance.

PMID- 21742969
TI  - NKT cells inhibit antigen-specific effector CD8 T cell induction to skin viral
      proteins.
AB  - We recently demonstrated that CD1d-restricted NKT cells resident in skin can
      inhibit CD8 T cell-mediated graft rejection of human papillomavirus E7-expressing
      skin through an IFN-gamma-dependent mechanism. In this study, we examined the
      role of systemically derived NKT cells in regulating the rejection of skin grafts
      expressing viral proteins. In lymph nodes draining transplanted skin, Ag-specific
      CD8 T cell proliferation, cytokine production, and cytotoxic activity were
      impaired by NKT cells. NKT cell suppression was mediated via CD11c(+) dendritic
      cells. Inhibition of CD8 T cell function did not require Foxp3(+) regulatory T
      cells or NKT cell-secreted IFN-gamma, IL-10, or IL-17. Thus, following skin
      grafting or immunization with human papillomavirus-E7 oncoprotein, NKT cells
      reduce the capacity of draining lymph node-resident APCs to cross-present Ag to
      CD8 T cell precursors, as evidenced by impaired expansion and differentiation to
      Ag-specific CD8 T effector cells. Therefore, in the context of viral Ag challenge
      in the skin, systemic NKT cells limit the capacity for effective priming of
      adaptive immunity.

PMID- 21742970
TI  - Repair of chromosomal RAG-mediated DNA breaks by mutant RAG proteins lacking
      phosphatidylinositol 3-like kinase consensus phosphorylation sites.
AB  - Ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic
      subunits (DNA-PKcs) are members of the phosphatidylinositol 3-like family of
      serine/threonine kinases that phosphorylate serines or threonines when positioned
      adjacent to a glutamine residue (SQ/TQ). Both kinases are activated rapidly by
      DNA double-strand breaks (DSBs) and regulate the function of proteins involved in
      DNA damage responses. In developing lymphocytes, DSBs are generated during V(D)J
      recombination, which is required to assemble the second exon of all Ag receptor
      genes. This reaction is initiated through a DNA cleavage step by the RAG1 and
      RAG2 proteins, which together comprise an endonuclease that generates DSBs at the
      border of two recombining gene segments and their flanking recombination signals.
      This DNA cleavage step is followed by a joining step, during which pairs of DNA
      coding and signal ends are ligated to form a coding joint and a signal joint,
      respectively. ATM and DNA-PKcs are integrally involved in the repair of both
      signal and coding ends, but the targets of these kinases involved in the repair
      process have not been fully elucidated. In this regard, the RAG1 and RAG2
      proteins, which each have several SQ/TQ motifs, have been implicated in the
      repair of RAG-mediated DSBs. In this study, we use a previously developed
      approach for studying chromosomal V(D)J recombination that has been modified to
      allow for the analysis of RAG1 and RAG2 function. We show that phosphorylation of
      RAG1 or RAG2 by ATM or DNA-PKcs at SQ/TQ consensus sites is dispensable for the
      joining step of V(D)J recombination.

PMID- 21742971
TI  - Lung tumor-associated dendritic cell-derived amphiregulin increased cancer
      progression.
AB  - The interaction of cancer within a microenvironment is an important factor
      determining cancer development. This study analyzed the soluble factors secreted
      by tumor-associated dendritic cells (TADCs), which are responsible for increasing
      lung cancer growth, migration, invasion, and epithelial-to-mesenchymal
      transition. Addition of amphiregulin, present in large amounts in TADC
      conditioned medium (CM), mimicked the inductive effect of TADC-CM on lung cancer
      progression, supported by the enhancement of cell proliferation, migration, and
      invasion as well as osteolytic bone metastases phenotypes. In contrast,
      neutralization of amphiregulin from TADC-CM decreased the advanced malignancy
      inductive properties of TADC-CM. Significant upregulation of amphiregulin has
      been seen in tumor-infiltrating CD11c(+) DCs in human lung cancer samples and
      patients' sera. The enhancement of amphiregulin in TADCs has also been noted in
      mice transplanted with lung cancer cells. Induction of lung cancer progression by
      TADC-derived amphiregulin is associated with increased STAT3 and AKT activation,
      which subsequently increases the expression of cyclin D, Twist, and Snail.
      Blocking AKT significantly decreases TADC-CM and amphiregulin-mediated migration
      by decreasing the upregulation of Snail, whereas inhibition of STAT3 reduced the
      modulation of TADC-derived amphiregulin on Twist and cyclin D expression,
      suggesting that cooperation of STAT3 and AKT plays a critical role in TADC
      mediated cancer progression. Moreover, mice treated with anti-amphiregulin Abs
      showed decreased incidence of cancer development and increased survival rates.
      Our study suggests that inhibition of amphiregulin or amphiregulin-related
      signaling is an attractive therapeutic target in lung cancer patients.

PMID- 21742972
TI  - Interaction with FcgammaRIIB is critical for the agonistic activity of anti-CD40
      monoclonal antibody.
AB  - A high activatory/inhibitory FcgammaR binding ratio is critical for the activity
      of mAb such as rituximab and alemtuzumab that attack cancer cells directly and
      eliminate them by recruiting immune effectors. Optimal FcgammaR binding profiles
      of other anti-cancer mAb, such as immunostimulatory mAb that stimulate or block
      immune receptors, are less clear. In this study, we analyzed the importance of
      isotype and FcgammaR interactions in controlling the agonistic activity of the
      anti-mouse CD40 mAb 3/23. Mouse IgG1 (m1) and IgG2a (m2a) variants of the
      parental 3/23 (rat IgG2a) were engineered and used to promote humoral and
      cellular responses against OVA. The mouse IgG1 3/23 was highly agonistic and
      outperformed the parental Ab when promoting Ab (10-100-fold) and T cell (OTI and
      OTII) responses (2- to >10-fold). In contrast, m2a was almost completely
      inactive. Studies in FcgammaR knockout mice demonstrated a critical role for the
      inhibitory FcgammaRIIB in 3/23 activity, whereas activatory FcgammaR (FcgammaRI, 
      III, and -IV) was dispensable. In vitro experiments established that the
      stimulatory effect of FcgammaRIIB was mediated through Ab cross-linking delivered
      in trans between neighboring cells and did not require intracellular signaling.
      Intriguingly, activatory FcgammaR provided effective cross-linking of 3/23 m2a in
      vitro, suggesting the critical role of FcgammaRIIB in vivo reflects its cellular
      distribution and bioavailability as much as its affinity for a particular Ab
      isotype. In conclusion, we demonstrate an essential cross-linking role for the
      inhibitory FcgammaRIIB in anti-CD40 immunostimulatory activity and suggest that
      isotype will be an important issue when optimizing reagents for clinical use.

PMID- 21742973
TI  - IDO induces expression of a novel tryptophan transporter in mouse and human tumor
      cells.
AB  - IDO is the rate-limiting enzyme in the kynurenine pathway, catabolizing
      tryptophan to kynurenine. Tryptophan depletion by IDO-expressing tumors is a
      common mechanism of immune evasion inducing regulatory T cells and inhibiting
      effector T cells. Because mammalian cells cannot synthesize tryptophan, it
      remains unclear how IDO(+) tumor cells overcome the detrimental effects of local
      tryptophan depletion. We demonstrate that IDO(+) tumor cells express a novel
      amino acid transporter, which accounts for ~50% of the tryptophan uptake. The
      induced transporter is biochemically distinguished from the constitutively
      expressed tryptophan transporter System L by increased resistance to inhibitors
      of System L, resistance to inhibition by high concentrations of most amino acids
      tested, and high substrate specificity for tryptophan. Under conditions of low
      extracellular tryptophan, expression of this novel transporter significantly
      increases tryptophan entry into IDO(+) tumors relative to tryptophan uptake
      through the low-affinity System L alone, and further decreases tryptophan levels
      in the microenvironment. Targeting this additional tryptophan transporter could
      be a way of pharmacological inhibition of IDO-mediated tumor escape. These
      findings highlight the ability of IDO-expressing tumor cells to thrive in a
      tryptophan-depleted microenvironment by expressing a novel, highly tryptophan
      specific transporter, which is resistant to inhibition by most other amino acids.
      The additional transporter allows tumor cells to strike the ideal balance between
      supply of tryptophan essential for their own proliferation and survival, and
      depleting the extracellular milieu of tryptophan to inhibit T cell proliferation.

PMID- 21742974
TI  - Inhibition of microRNA let-7i depresses maturation and functional state of
      dendritic cells in response to lipopolysaccharide stimulation via targeting
      suppressor of cytokine signaling 1.
AB  - Dendritic cells (DCs) can initiate immune responses or confer immune tolerance
      depending on functional status. LPS-induced DC maturation is defined by enhanced
      surface expression of CD80 and CD86. MicroRNAs are critical for the regulation of
      DC function and immunity, and the microRNA let-7i was upregulated during LPS
      induced DC maturation. Downregulation of let-7i significantly impeded DC
      maturation as evidenced by reduced CD80 and CD86 expression. DCs stimulated by
      LPS promoted T cell proliferation in coculture, whereas LPS-stimulated DCs with
      downregulated let-7i were not effective at stimulating T cell proliferation but
      promoted expansion of the regulatory T cell (Treg) population. There were two
      subpopulations of LPS-stimulated DCs with downregulated let-7i, CD86(-) and
      CD86(+), and it was the CD86(-) DCs that were more effective in inducing T cell
      hyporesponsiveness and enhancing Treg numbers, indicating that this DC population
      had tolerogenic properties. Furthermore, Tregs with upregulated IL-10 underscored
      the tolerogenic effect of CD86(-) DCs. Suppressor of cytokine signaling 1
      (SOCS1), a crucial mediator of DC maturation, was confirmed as a let-7i target
      gene by luciferase construct assay. Suppression or overexpression of let-7i
      caused reciprocal alterations in SOCS1 protein expression, but had no significant
      effects on SOCS1 mRNA levels, indicating that let-7i regulated SOCS1 expression
      by translational suppression. The modulation of SOCS1 protein by let-7i was
      mainly restricted to CD86(-) DCs. Our study demonstrates that let-7i regulation
      of SOCS1 is critical for LPS-induced DC maturation and immune function. Dynamic
      regulation of let-7i may fine-tune immune responses by inducing Ag-specific
      immune tolerance.

PMID- 21742975
TI  - 4-1BB signaling synergizes with programmed death ligand 1 blockade to augment CD8
      T cell responses during chronic viral infection.
AB  - Previous studies have identified the inhibitory role that the programmed death 1
      (PD-1) pathway plays during chronic infection. Blockade of this pathway results
      in rescue of viral-specific CD8 T cells, as well as reduction of viral loads in
      mice chronically infected with lymphocytic choriomeningitis virus (LCMV). We
      tested the effect of combining PD ligand 1 (PD-L1) blockade with an agonistic
      regimen that induces 4-1BB costimulation during chronic LCMV infection. There is
      a boosting effect in the rescue of LCMV-specific CD8 T cell responses after dual
      treatment with PD-L1 blockade and 4-1BB agonistic Abs when the amount and timing
      of 4-1BB costimulation are carefully controlled. When PD-L1-blocking Abs are
      given together with a single low dose of anti-4-1BB agonistic Abs, there is an
      enhanced and stable expansion of viral-specific CD8 T cells. Conversely, when
      blocking Abs to PD-L1 are given with a repetitive high dose of anti-4-1BB, there
      is an initial synergistic expansion of viral-specific CD8 T cells by day 7,
      followed by dramatic apoptosis by day 14. Viral control paralleled CD8 T cell
      kinetics after dual treatment. By day 7 posttreatment, viral titers were lower in
      both of the combined regimens (compared with PD-L1 blockade alone). However,
      whereas the high dose of anti-4-1BB plus PD-L1 blockade resulted in rebound of
      viral titers to original levels, the low dose of anti-4-1BB plus PD-L1 blockade
      resulted in a stable reduction of viral loads. These findings demonstrate the
      importance of carefully manipulating the balance between activating and
      inhibitory signals to enhance T cell responses during chronic infection.

PMID- 21742976
TI  - Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells
      while preserving regulatory T cells.
AB  - Monoclonal anti-CD3 Abs have been used clinically for two decades to reverse
      steroid-resistant acute graft rejection. In autoimmune diabetes, short course
      treatment with FcR-nonbinding (FNB) anti-CD3 mAb in mice with recent onset of
      diabetes induces long-term disease remission. Induction of tolerogenic regulatory
      T cells (Tregs) has been implicated to be one of the mechanisms of action by FNB
      anti-CD3 mAb in these settings. In this study, we examined the effect of FNB anti
      CD3 mAb treatment on the homeostasis of naive, effector, and regulatory T cells
      in vivo. Anti-CD3 treatment induced a transient systemic rise in the percentage
      but not absolute number of CD4(+)Foxp3(+) Tregs due to selective depletion of
      CD4(+)Foxp3(-) conventional T cells. T cell depletion induced by FNB anti-CD3 mAb
      was independent of the proapoptotic proteins Fas, caspase-3, and Bim and was not
      inhibited by overexpression of the anti-apoptotic protein, Bcl-2. Tregs were not
      preferentially expanded and we found no evidence of conversion of conventional T
      cells into Tregs, suggesting that the pre-existing Tregs are resistant to anti
      CD3-induced cell death. Interestingly, expression of the transcription factor
      Helios, which is expressed by thymus-derived natural Tregs, was increased in
      Tregs after FNB anti-CD3 mAb treatment, suggesting that the anti-CD3 treatment
      can alter, and potentially stabilize, Treg function. Taken together, the results
      suggest that FNB anti-CD3 therapy promotes tolerance by restoring the balance
      between pathogenic and regulatory T cells.

PMID- 21742977
TI  - Deficiency of the leukotriene B4 receptor, BLT-1, protects against systemic
      insulin resistance in diet-induced obesity.
AB  - Chronic inflammation is an underlying factor linking obesity with insulin
      resistance. Diet-induced obesity promotes an increase in circulating levels of
      inflammatory monocytes and their infiltration into expanding adipose tissue.
      Nevertheless, the endogenous pathways that trigger and sustain chronic low-grade
      inflammation in obesity are incompletely understood. In this study, we report
      that a high-fat diet selectively increases the circulating levels of CD11b(+)
      monocytes in wild-type mice that express leukotriene B(4) receptor, BLT-1, and
      that this increase is abolished in BLT-1-null mice. The accumulation of
      classically activated (M1) adipose tissue macrophages (ATMs) and the expression
      of proinflammatory cytokines and chemokines (i.e., IL-6 and Ccl2) was largely
      blunted in adipose tissue of obese BLT-1(-/-) mice, whereas the ratio of
      alternatively activated (M2) ATMs to M1 ATMs was increased. Obese BLT-1(-/-) mice
      were protected from systemic glucose and insulin intolerance and this was
      associated with a decrease in inflammation in adipose tissue and liver and a
      decrease in hepatic triglyceride accumulation. Deletion of BLT-1 prevented high
      fat-induced loss of insulin signaling in liver and skeletal muscle. These
      observations elucidate a novel role of chemoattractant receptor, BLT-1, in
      promoting monocyte trafficking to adipose tissue and promoting chronic
      inflammation in obesity and could lead to the identification of new therapeutic
      targets for treating insulin resistance in obesity.

PMID- 21742978
TI  - Processing of human protryptase in mast cells involves cathepsins L, B, and C.
AB  - Human beta-tryptase is stored in secretory granules of human mast cells as a
      heparin-stabilized tetramer. beta-Protryptase in solution can be directly
      processed to the mature enzyme by cathepsin (CTS) L and CTSB, and sequentially
      processed by autocatalysis at R(-3), followed by CTSC proteolysis. However, it is
      uncertain which CTS is involved in protryptase processing inside human mast
      cells, because murine bone marrow-derived mast cells from CTSC-deficient mice
      convert protryptase (pro-mouse mast cell protease-6) to mature mouse mast cell
      protease-6. This finding suggests that other proteases are important for
      processing human beta-protryptase. In the current study, reduction of either CTSB
      or CTSL activity inside HMC-1 cells by short hairpin RNA silencing or CTS
      specific pharmacologic inhibitors substantially reduced mature beta-tryptase
      formation. Similar reductions of tryptase levels in primary skin-derived mast
      cells were observed with these pharmacologic inhibitors. In contrast, protryptase
      processing was minimally reduced by short hairpin RNA silencing of CTSC. A
      putative pharmacologic inhibitor of CTSC markedly reduced tryptase levels,
      suggesting an off-target effect. Skin mast cells contain substantially greater
      amounts of CTSL and CTSB than do HMC-1 cells, the opposite being found for CTSC.
      Both CTSL and CTSB colocalize to the secretory granule compartment of skin mast
      cells. Thus, CTSL and CTSB are central to the processing of protryptase(s) in
      human mast cells and are potential targets for attenuating production of mature
      tryptase in vivo.

PMID- 21742979
TI  - Aerosol-cloud-precipitation system as a predator-prey problem.
AB  - We show that the aerosol-cloud-precipitation system exhibits characteristics of
      the predator-prey problem in the field of population dynamics. Both a detailed
      large eddy simulation of the dynamics and microphysics of a precipitating shallow
      boundary layer cloud system and a simpler model built upon basic physical
      principles, reproduce predator-prey behavior with rain acting as the predator and
      cloud as the prey. The aerosol is shown to modulate the predator-prey response.
      Steady-state solution to the proposed model shows the known existence of
      bistability in cloudiness. Three regimes are identified in the time-dependent
      solutions: (i) the weakly precipitating regime where cloud and rain coexist in a
      quasi steady state; (ii) the moderately drizzling regime where limit-cycle
      behavior in the cloud and rain fields is produced; and (iii) the heavily
      precipitating clouds where collapse of the boundary layer is predicted. The
      manifestation of predator-prey behavior in the aerosol-cloud-precipitation system
      is a further example of the self-organizing properties of the system and suggests
      that exploiting principles of population dynamics may help reduce complex aerosol
      cloud-rain interactions to a more tractable problem.

PMID- 21742980
TI  - Separation of preferential interaction and excluded volume effects on DNA duplex
      and hairpin stability.
AB  - Small solutes affect protein and nucleic acid processes because of favorable or
      unfavorable chemical interactions of the solute with the biopolymer surface
      exposed or buried in the process. Large solutes also exclude volume and affect
      processes where biopolymer molecularity and/or shape changes. Here, we develop an
      analysis to separate and interpret or predict excluded volume and chemical
      effects of a flexible coil polymer on a process. We report a study of the
      concentration-dependent effects of the full series from monomeric to polymeric
      PEG on intramolecular hairpin and intermolecular duplex formation by 12
      nucleotide DNA strands. We find that chemical effects of PEG on these processes
      increase in proportion to the product of the amount of DNA surface exposed on
      melting and the amount of PEG surface that is accessible to this DNA, and these
      effects are completely described by two interaction terms that quantify the
      interactions between this DNA surface and PEG end and interior groups. We find
      that excluded volume effects, once separated from these chemical effects, are
      quantitatively described by the analytical theory of Hermans, which predicts the
      excluded volume between a flexible polymer and a rigid molecule. From this
      analysis, we show that at constant concentration of PEG monomer, increasing PEG
      size increases the excluded volume effect but decreases the chemical interaction
      effect, because in a large PEG coil a smaller fraction of the monomers are
      accessible to the DNA. Volume exclusion by PEG has a much larger effect on
      intermolecular duplex formation than on intramolecular hairpin formation.

PMID- 21742981
TI  - Quantifying the sequence-function relation in gene silencing by bacterial small
      RNAs.
AB  - Sequence-function relations for small RNA (sRNA)-mediated gene silencing were
      quantified for the sRNA RyhB and some of its mRNA targets in Escherichia coli.
      Numerous mutants of RyhB and its targets were generated and their in vivo
      functions characterized at various levels of target and RyhB expression. Although
      a core complementary region is required for repression by RyhB, variations in the
      complementary sequences of the core region gave rise to a continuum of repression
      strengths, correlated exponentially with the computed free energy of RyhB-target
      duplex formation. Moreover, sequence variations in the linker region known to
      interact with the RNA chaperone Hfq also gave rise to a continuum of repression
      strengths, correlated exponentially with the computed energy cost of keeping the
      linker region open. These results support the applicability of the thermodynamic
      model in predicting sRNA-mRNA interaction and suggest that sequences at these
      locations may be used to fine-tune the degree of repression. Surprisingly, a
      truncated RyhB without the Hfq-binding region is found to repress multiple
      targets of the wild-type RyhB effectively, both in the presence and absence of
      Hfq, even though the former is required for the activity of wild-type RyhB
      itself. These findings challenge the commonly accepted model concerning the
      function of Hfq in gene silencing-both in providing stability to the sRNAs and in
      catalyzing the target mRNAs to take on active conformations-and raise the
      intriguing question of why many endogenous sRNAs subject their functions to Hfq
      dependences.

PMID- 21742982
TI  - Bayesian sampling in visual perception.
AB  - It is well-established that some aspects of perception and action can be
      understood as probabilistic inferences over underlying probability distributions.
      In some situations, it would be advantageous for the nervous system to sample
      interpretations from a probability distribution rather than commit to a
      particular interpretation. In this study, we asked whether visual percepts
      correspond to samples from the probability distribution over image
      interpretations, a form of sampling that we refer to as Bayesian sampling. To
      test this idea, we manipulated pairs of sensory cues in a bistable display
      consisting of two superimposed moving drifting gratings, and we asked subjects to
      report their perceived changes in depth ordering. We report that the fractions of
      dominance of each percept follow the multiplicative rule predicted by Bayesian
      sampling. Furthermore, we show that attractor neural networks can sample
      probability distributions if input currents add linearly and encode probability
      distributions with probabilistic population codes.

PMID- 21742983
TI  - Social-ecological interactions, management panaceas, and the future of wild fish
      populations.
AB  - We explored the social and ecological outcomes associated with emergence of a
      management panacea designed to govern a stochastic renewable natural resource. To
      that end, we constructed a model of a coupled social-ecological system of
      recreational fisheries in which a manager supports naturally fluctuating stocks
      by stocking fish in response to harvest-driven satisfaction of resource users.
      The realistic assumption of users remembering past harvest experiences when
      exploiting a stochastically fluctuating fish population facilitates the emergence
      of a stocking-based management panacea over time. The social benefits of panacea
      formation involve dampening natural population fluctuations and generating
      stability of user satisfaction. It also maintains the resource but promotes the
      eventual replacement of wild fish by hatchery-descended fish. Our analyses show
      this outcome is particularly likely when hatchery-descended fish are reasonably
      fit (e.g., characterized by similar survival relative to wild fish) and/or when
      natural recruitment of the wild population is low (e.g., attributable to habitat
      deterioration), which leaves the wild population with little buffer against
      competition by stocked fish. The potential for release-based panacea formation is
      particularly likely under user-based management regimes and should be common in a
      range of social-ecological systems (e.g., fisheries, forestry), whenever user
      groups are entitled to engage in release or replanting strategies. The net result
      will be the preservation of a renewable resource through user-based incentives,
      but the once natural populations are likely to be altered and to host nonnative
      genotypes. This risks other ecosystem services and the future of wild
      populations.

PMID- 21742984
TI  - Timing of the appearance of habitual fire use.

PMID- 21742985
TI  - Weak points in competitive network theory of species diversity.

PMID- 21742986
TI  - The FRD3 citrate effluxer promotes iron nutrition between symplastically
      disconnected tissues throughout Arabidopsis development.
AB  - We present data supporting a general role for FERRIC REDICTASE DEFECTIVE3 (FRD3),
      an efflux transporter of the efficient iron chelator citrate, in maintaining iron
      homeostasis throughout plant development. In addition to its well-known
      expression in root, we show that FRD3 is strongly expressed in Arabidopsis
      thaliana seed and flower. Consistently, frd3 loss-of-function mutants are
      defective in early germination and are almost completely sterile, both defects
      being rescued by iron and/or citrate supply. The frd3 fertility defect is caused
      by pollen abortion and is associated with the male gametophytic expression of
      FRD3. Iron imaging shows the presence of important deposits of iron on the
      surface of aborted pollen grains. This points to a role for FRD3 and citrate in
      proper iron nutrition of embryo and pollen. Based on the findings that iron
      acquisition in embryo, leaf, and pollen depends on FRD3, we propose that FRD3
      mediated-citrate release in the apoplastic space represents an important process
      by which efficient iron nutrition is achieved between adjacent tissues lacking
      symplastic connections. These results reveal a physiological role for citrate in
      the apoplastic transport of iron throughout development, and provide a general
      model for multicellular organisms in the cell-to-cell transport of iron involving
      extracellular circulation.

PMID- 21742987
TI  - Origins and recombination of the bacterial-sized multichromosomal mitochondrial
      genome of cucumber.
AB  - Members of the flowering plant family Cucurbitaceae harbor the largest known
      mitochondrial genomes. Here, we report the 1685-kb mitochondrial genome of
      cucumber (Cucumis sativus). We help solve a 30-year mystery about the origins of
      its large size by showing that it mainly reflects the proliferation of dispersed
      repeats, expansions of existing introns, and the acquisition of sequences from
      diverse sources, including the cucumber nuclear and chloroplast genomes, viruses,
      and bacteria. The cucumber genome has a novel structure for plant mitochondria,
      mapping as three entirely or largely autonomous circular chromosomes (lengths
      1556, 84, and 45 kb) that vary in relative abundance over a twofold range. These
      properties suggest that the three chromosomes replicate independently of one
      another. The two smaller chromosomes are devoid of known functional genes but
      nonetheless contain diagnostic mitochondrial features. Paired-end sequencing
      conflicts reveal differences in recombination dynamics among chromosomes, for
      which an explanatory model is developed, as well as a large pool of low-frequency
      genome conformations, many of which may result from asymmetric recombination
      across intermediate-sized and sometimes highly divergent repeats. These findings
      highlight the promise of genome sequencing for elucidating the recombinational
      dynamics of plant mitochondrial genomes.

PMID- 21742988
TI  - Independent recruitment of an O-methyltransferase for syringyl lignin
      biosynthesis in Selaginella moellendorffii.
AB  - Syringyl lignin, an important component of the secondary cell wall, has
      traditionally been considered to be a hallmark of angiosperms because ferns and
      gymnosperms in general lack lignin of this type. Interestingly, syringyl lignin
      was also detected in Selaginella, a genus that represents an extant lineage of
      the most basal of the vascular plants, the lycophytes. In angiosperms, syringyl
      lignin biosynthesis requires the activity of ferulate 5-hydroxylase (F5H), a
      cytochrome P450-dependent monooxygenase, and caffeic acid/5-hydroxyferulic acid O
      methyltransferase (COMT). Together, these two enzymes divert metabolic flux from
      the biosynthesis of guaiacyl lignin, a lignin type common to all vascular plants,
      toward syringyl lignin. Selaginella has independently evolved an alternative
      lignin biosynthetic pathway in which syringyl subunits are directly derived from
      the precursors of p-hydroxyphenyl lignin, through the action of a dual
      specificity phenylpropanoid meta-hydroxylase, Sm F5H. Here, we report the
      characterization of an O-methyltransferase from Selaginella moellendorffii, COMT,
      the coding sequence of which is clustered together with F5H at the adjacent
      genomic locus. COMT is a bifunctional phenylpropanoid O-methyltransferase that
      can methylate phenylpropanoid meta-hydroxyls at both the 3- and 5-position and
      function in concert with F5H in syringyl lignin biosynthesis in S.
      moellendorffii. Phylogenetic analysis reveals that Sm COMT, like F5H, evolved
      independently from its angiosperm counterparts.

PMID- 21742991
TI  - Arabidopsis class I KNOTTED-like homeobox proteins act downstream in the IDA
      HAE/HSL2 floral abscission signaling pathway.
AB  - Floral organ abscission in Arabidopsis thaliana is regulated by the putative
      ligand-receptor system comprising the signaling peptide INFLORESCENCE DEFICIENT
      IN ABSCISSION (IDA) and the two receptor-like kinases HAESA and HAESA-LIKE2. The
      IDA signaling pathway presumably activates a MITOGEN-ACTIVATED PROTEIN KINASE
      (MAPK) cascade to induce separation between abscission zone (AZ) cells.
      Misexpression of IDA effectuates precocious floral abscission and ectopic cell
      separation in latent AZ cell regions, which suggests that negative regulators are
      in place to prevent unrestricted and untimely AZ cell separation. Through a
      screen for mutations that restore floral organ abscission in ida mutants, we
      identified three new mutant alleles of the KNOTTED-LIKE HOMEOBOX gene
      BREVIPEDICELLUS (BP)/KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1). Here, we
      show that bp mutants, in addition to shedding their floral organs prematurely,
      have phenotypic commonalities with plants misexpressing IDA, such as enlarged AZ
      cells. We propose that BP/KNAT1 inhibits floral organ cell separation by
      restricting AZ cell size and number and put forward a model whereby IDA signaling
      suppresses BP/KNAT1, which in turn allows KNAT2 and KNAT6 to induce floral organ
      abscission.

PMID- 21742992
TI  - Differential regulation of cellulose orientation at the inner and outer face of
      epidermal cells in the Arabidopsis hypocotyl.
AB  - It is generally believed that cell elongation is regulated by cortical
      microtubules, which guide the movement of cellulose synthase complexes as they
      secrete cellulose microfibrils into the periplasmic space. Transversely oriented
      microtubules are predicted to direct the deposition of a parallel array of
      microfibrils, thus generating a mechanically anisotropic cell wall that will
      favor elongation and prevent radial swelling. Thus far, support for this model
      has been most convincingly demonstrated in filamentous algae. We found that in
      etiolated Arabidopsis thaliana hypocotyls, microtubules and cellulose synthase
      trajectories are transversely oriented on the outer surface of the epidermis for
      only a short period during growth and that anisotropic growth continues after
      this transverse organization is lost. Our data support previous findings that the
      outer epidermal wall is polylamellate in structure, with little or no anisotropy.
      By contrast, we observed perfectly transverse microtubules and microfibrils at
      the inner face of the epidermis during all stages of cell expansion. Experimental
      perturbation of cortical microtubule organization preferentially at the inner
      face led to increased radial swelling. Our study highlights the previously
      underestimated complexity of cortical microtubule organization in the shoot
      epidermis and underscores a role for the inner tissues in the regulation of
      growth anisotropy.

PMID- 21742993
TI  - Symbiotic rhizobia bacteria trigger a change in localization and dynamics of the
      Medicago truncatula receptor kinase LYK3.
AB  - To form nitrogen-fixing symbioses, legume plants recognize a bacterial signal,
      Nod Factor (NF). The legume Medicago truncatula has two predicted NF receptors
      that direct separate downstream responses to its symbiont Sinorhizobium meliloti.
      NOD FACTOR PERCEPTION encodes a putative low-stringency receptor that is
      responsible for calcium spiking and transcriptional responses. LYSIN MOTIF
      RECEPTOR-LIKE KINASE3 (LYK3) encodes a putative high-stringency receptor that
      mediates bacterial infection. We localized green fluorescent protein (GFP)-tagged
      LYK3 in M. truncatula and found that it has a punctate distribution at the cell
      periphery consistent with a plasma membrane or membrane-tethered vesicle
      localization. In buffer-treated control roots, LYK3:GFP puncta are dynamic. After
      inoculation with compatible S. meliloti, LYK3:GFP puncta are relatively stable.
      We show that increased LYK3:GFP stability depends on bacterial NF and NF
      structure but that NF is not sufficient for the change in LYK3:GFP dynamics. In
      uninoculated root hairs, LYK3:GFP has little codistribution with mCherry-tagged
      FLOTILLIN4 (FLOT4), another punctate plasma membrane-associated protein required
      for infection. In inoculated root hairs, we observed an increase in FLOT4:mCherry
      and LYK3:GFP colocalization; both proteins localize to positionally stable
      puncta. We also demonstrate that the localization of tagged FLOT4 is altered in
      plants carrying a mutation that inactivates the kinase domain of LYK3. Our work
      indicates that LYK3 protein localization and dynamics are altered in response to
      symbiotic bacteria.

PMID- 21742994
TI  - Distinct cell-autonomous functions of RETINOBLASTOMA-RELATED in Arabidopsis stem
      cells revealed by the Brother of Brainbow clonal analysis system.
AB  - Mutations that cause lethality in the gametophyte phase pose a major challenge
      for studying postfertilization gene function. When both male and female haploid
      cells require a functional gene copy, null alleles cause developmental arrest
      before the formation of the zygote, precluding further investigation. The
      Arabidopsis thaliana Rb homolog RETINOBLASTOMA-RELATED (RBR) has an important
      function in the stem cell niche, but its requirement in both male and female
      gametophytes has prevented full loss-of-function studies. To circumvent this
      obstacle, we designed a clonal deletion system named BOB (Brother of Brainbow) in
      which null mutant sectors marked by double fluorescence are generated in a fully
      complemented wild-type background. In this system, both copies of a complementing
      RBR transgene are eliminated by tissue-specific and inducible CRE expression, and
      homozygous mutant clones can be distinguished visually. Since mutant sectors can
      be produced in a homozygous, rather than a heterozygous, background, this system
      facilitates clonal deletion analysis not only for gametophytic lethal alleles but
      also for any type of mutation. Using the BOB system, we show that RBR has unique
      cell-autonomous functions in different cell types within the root stem cell
      niche.

PMID- 21742996
TI  - Catecholaminergic-induced arrhythmias in failing cardiomyocytes associated with
      human HRCS96A variant overexpression.
AB  - The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown
      to correlate with ventricular arrhythmias and sudden death only in dilated
      cardiomyopathy patients but not in healthy human carriers. In the present study,
      we assessed the molecular and cellular mechanisms underlying human arrhythmias by
      adenoviral expression of the human wild-type (HRC(WT)) or mutant HRC (HRC(S96A))
      in adult rat ventricular cardiomyocytes. Total HRC protein was increased by ~50%
      in both HRC(WT)- and HRC(S96A)-infected cells. The HRC(S96A) mutant exacerbated
      the inhibitory effects of HRC(WT) on the amplitude of Ca(2+) transients,
      prolongation of Ca(2+) decay time, and caffeine-induced sarcoplasmic reticulum
      Ca(2+) release. Consistent with these findings, HRC(S96A) reduced maximal
      sarcoplasmic reticulum calcium uptake rate to a higher extent than HRC(WT).
      Furthermore, the frequency of spontaneous Ca(2+) sparks, which was reduced by
      HRC(WT), was increased by mutant HRC(S96A) under resting conditions although
      there were no spontaneous Ca(2+) waves under stress conditions. However,
      expression of the HRC(S96A) genetic variant in cardiomyocytes from a rat model of
      postmyocardial infarction heart failure induced dramatic disturbances of rhythmic
      Ca(2+) transients. These findings indicate that the HRC Ser96Ala variant
      increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing
      heart, suggesting a link between this genetic variant and life-threatening
      ventricular arrhythmias in human carriers.

PMID- 21742997
TI  - Arteriolar reactivity in lymphocyte-deficient mice.
AB  - Mounting evidence suggests that lymphocytes have the capacity to contribute to
      the regulation of systemic circulatory control. We postulated that T and natural
      killer (NK) cells could modify basal microvascular activity under physiologically
      normal conditions. In situ intravital microscopy of mouse cremaster vasculature
      was used to evaluate arteriolar reactivities to the vasoconstrictors angiotensin
      II (ANG II) and phenylephrine (Phe) and the vasodilators acetylcholine (ACh) and
      adenosine (Ado) in normal [+/+; wild type (WT)] and genetically immunodeficient
      (T(-)B(-)NK(+) or T(-)B(-)?NK(-)) C57BL/6 and BALB/c mice, strain backgrounds
      with differentially polarized T cell cytokine production. Immunodeficient mice
      tended to have smaller baseline and maximal diameters of third-order cremaster
      arterioles than their congenic WT partners. In C57BL/6, baseline diameters were
      similar in T-B(-) mice without or with NK cells; in BALB/c, baseline diameters
      were larger in T-B-NK(-) mice than in T(-)B(-)NK(+) mice. Thus, at baseline,
      lymphocytes tended to promote vasodilation, except BALB/c NK cells, which
      mediated mild vasoconstriction. The presence of NK cells suppressed dilations to
      Ado in both strains, to ACh in the C57BL/6 strain, and dilatory responses to ANG
      II in C57BL/6 and to Phe in BALB/c. In the BALB/c strain, the presence of T and B
      cells promoted vasodilatory responses to Ado, attenuated dilations to low ACh
      concentrations, and exaggerated dilation and constriction responses to ANG II.
      Thus, under agonist challenge, NK cells generally promote constriction, whereas
      influences of T and B cells depend upon the stimulus. Therefore, lymphocytes or
      their products have physiological influences on microvascular arteriolar
      reactivity.

PMID- 21742998
TI  - Targeting intracellular calcium cycling in catecholaminergic polymorphic
      ventricular tachycardia: a theoretical investigation.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant
      arrhythmogenic disorder linked to mutations in the cardiac ryanodine receptor
      (RyR2) and calsequestrin, predisposing the young to syncope and cardiac arrest.
      To define the role of beta-adrenergic stimulation (BAS) and to identify potential
      therapeutic targeted sites relating to intracellular calcium cycling, we used a
      Luo-Rudy dynamic ventricular myocyte model incorporated with interacting Markov
      models of the L-type Ca(2+) channel (I(Ca,L)) and RyR2 to simulate the
      heterozygous state of mouse RyR2 R4496C mutation (RyR2(R4496C+/-)) comparable
      with CPVT patients with RyR2 R4497C mutation. Characteristically, in simulated
      cells, pacing at 4 Hz or faster or pacing at 2 Hz under BAS with effects
      equivalent to those of isoproterenol at >= 0.1 MUM could readily induce delayed
      afterdepolarizations (DADs) and DAD-mediated triggered activity (TA) in
      RyR2(R4496C+/-) but not in the wild-type via enhancing both I(Ca,L) and
      sarcoplasmic reticulum (SR) Ca(2+) ATPase (I(UP)). Moreover, with the use of
      steady state values of isolated endocardial (Endo), mid-myocardial (M), and
      epicardial (Epi) cells as initial data for conducting single cell and one
      dimensional strand studies, the M cell was more vulnerable for developing DADs
      and DAD-mediated TA than Endo and Epi cells, and the gap junction coupling
      represented by diffusion coefficient (D) of <= 0.000766*98 cm(2)/ms was required
      for generating DAD-mediated TA in RyR2(R4496C+/-). Whereas individual reduction
      of Ca(2+) release channel of SR and Na-Ca exchanger up to 50% was ineffective,
      30% or more reduction of either I(Ca,L) or I(UP) could totally suppress the
      inducibility of arrhythmia under BAS. Of note, 15% reduction of both I(Ca,L) and
      I(UP) exerted a synergistic antiarrhythmic efficacy. Findings of this model study
      confirm that BAS facilitates induction of ventricular tachyarrhythmias via its
      action on intracellular Ca(2+) cycling and a pharmacological regimen capable of
      reducing I(Ca,L) could be an effective adjunctive to beta-adrenergic blockers for
      suppressing ventricular tachyarrhythmias during CPVT.

PMID- 21742999
TI  - Evidence for greater burden of peripheral arterial disease in lower extremity
      arteries of spinal cord-injured individuals.
AB  - Spinal cord injury leads to increased risk for cardiovascular disease and results
      in greater risk of death. Subclinical markers of atherosclerosis have been
      reported in carotid arteries of spinal cord-injured individuals (SCI), but the
      development of lower extremity peripheral arterial disease (PAD) has not been
      investigated in this population. The purpose of this study was to determine the
      effect of spinal cord injury on ankle-brachial index (ABI) and intima-media
      thickness (IMT) of upper-body and lower-extremity arteries. We hypothesized that
      the aforementioned measures of lower-extremity PAD would be worsened in SCI
      compared with controls and that regular participation in endurance exercise would
      improve these in both groups. To test these hypotheses, ABI and IMT were
      determined in 105 SCI and compared with 156 able-bodied controls with groups
      further subdivided into physically active and sedentary. ABIs were significantly
      lower in SCI versus controls (0.96 +/- 0.12 vs. 1.06 +/- 0.07, P < 0.001),
      indicating a greater burden of lower-extremity PAD. Upper-body IMTs were similar
      for brachial and carotid arteries in controls versus SCI. Lower extremity IMTs
      revealed similar thicknesses for both superficial femoral and popliteal arteries,
      but when normalized for artery diameter, individuals with SCI had greater IMT
      than controls in the superficial femoral (0.094 +/- 0.03 vs. 0.073 +/- 0.02 mm/mm
      lumen diameter, P < 0.01) and popliteal (0.117 +/- 0.04 vs. 0.091 +/- 0.02 mm/mm
      lumen diameter, P < 0.01) arteries. The ABI and normalized IMT of SCI compared
      with controls indicate that subclinical measures of lower-extremity PAD are
      worsened in individuals with SCI. These findings should prompt physicians to
      consider using the ABI as a screening method to detect lower-extremity PAD in
      SCI.

PMID- 21743000
TI  - Effects of nicotine administration in a mouse model of familial hypertrophic
      cardiomyopathy, alpha-tropomyosin D175N.
AB  - The effects of nicotine (NIC) on normal hearts are fairly well established, yet
      its effects on hearts displaying familial hypertrophic cardiomyopathy have not
      been tested. We studied both the acute and chronic effects of NIC on a transgenic
      (TG) mouse model of FHC caused by a mutation in alpha-tropomyosin (Tm; i.e.,
      alpha-Tm D175N TG, or Tm175). For acute effects, intravenously injected NIC
      increased heart rate, left ventricular (LV) pressure, and the maximal rate of LV
      pressure increase (+dP/dt) in non-TG (NTG) and Tm175 mice; however, Tm175 showed
      a significantly smaller increase in the maximal rate of LV pressure decrease (
      dP/dt) compared with NTGs. Western blots revealed phosphorylation of
      phospholamban Ser16 and Thr17 residue increased in NTG mice following NIC
      injection but not in Tm175 mice. In contrast, phosphorylation of troponin I at
      serine residues 23 and 24 increased equally in both NTG and Tm175. Thus the
      attenuated increase in relaxation in Tm175 mice following acute NIC appears to
      result primarily from attenuated phospholamban phosphorylation. Chronic NIC
      administration (equivalent to smoking 2 packs of cigarettes/day for 4 mo) also
      increased +dP/dt in NTG and Tm175 mice compared with chronic saline. However,
      chronic NIC had little effect on heart rate, LV pressure, -dP/dt, LV wall and
      chamber dimensions, or collagen content for either group of mice.

PMID- 21743001
TI  - Adenosine A2A and A2B receptors are both required for adenosine A1 receptor
      mediated cardioprotection.
AB  - All four adenosine receptor subtypes have been shown to play a role in
      cardioprotection, and there is evidence that all four subtypes may be expressed
      in cardiomyocytes. There is also increasing evidence that optimal adenosine
      cardioprotection requires the activation of more than one receptor subtype. The
      purpose of this study was to determine whether adenosine A(2A) and/or A(2B)
      receptors modulate adenosine A(1) receptor-mediated cardioprotection. Isolated
      perfused hearts of wild-type (WT), A(2A) knockout (KO), and A(2B)KO mice,
      perfused at constant pressure and constant heart rate, underwent 30 min of global
      ischemia and 60 min of reperfusion. The adenosine A(1) receptor agonist N(6)
      cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and
      for the first 10 min of reperfusion. Treatment with CHA significantly improved
      postischemic left ventricular developed pressure (74 +/- 4% vs. 44 +/- 4% of
      preischemic left ventricular developed pressure at 60 min of reperfusion) and
      reduced infarct size (30 +/- 2% with CHA vs. 52 +/- 5% in control) in WT hearts,
      effects that were blocked by the A(1) antagonist 8-cyclopentyl-1,3
      dipropylxanthine (100 nM). Treatments with the A(2A) receptor agonist CGS-21680
      (200 nM) and the A(2B) agonist BAY 60-6583 (200 nM) did not exert any beneficial
      effects. Deletion of adenosine A(2A) or A(2B) receptor subtypes did not alter
      ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in
      hearts of mice from either KO group. These findings indicate that both adenosine
      A(2A) and A(2B) receptors are required for adenosine A(1) receptor-mediated
      cardioprotection, implicating a role for interactions among receptor subtypes.

PMID- 21743002
TI  - Molecular determinants for activation of human ether-a-go-go-related gene 1
      potassium channels by 3-nitro-n-(4-phenoxyphenyl) benzamide.
AB  - Human ether-a-go-go-related gene 1 (hERG1) channels mediate repolarization of
      cardiac action potentials. Inherited long QT syndrome (LQTS) caused by loss-of
      function mutations, or unintended blockade of hERG1 channels by many drugs, can
      lead to severe arrhythmia and sudden death. Drugs that activate hERG1 are a novel
      pharmacological approach to treat LQTS. 3-Nitro-n-(4-phenoxyphenyl) benzamide
      [ICA-105574 (ICA)] has been discovered to activate hERG1 by strong attenuation of
      pore-type inactivation. Here, we used scanning mutagenesis of hERG1 to identify
      the molecular determinants of ICA action. Three mutations abolished the activator
      effects of 30 MUM ICA, including L622C in the pore helix, F557L in the S5
      segment, and Y652A in the S6 segment. One mutation in S6 (A653M) switched the
      activity of ICA from an activator to an inhibitor, revealing its partial agonist
      activity. This was confirmed by showing that the noninactivating mutant hERG1
      channel (G628C/S631C) was inhibited by ICA and that the addition of the F557L
      mutation rendered the channel drug-insensitive. Simulated molecular docking of
      ICA to homology models of hERG1 corroborated the scanning mutagenesis findings.
      Together, our findings indicate that ICA is a mixed agonist of hERG1 channels.
      Activation or inhibition of currents is mediated by the same or overlapping
      binding site located in the pore module between two adjacent subunits of the
      homotetrameric channel.

PMID- 21743003
TI  - Different roles of membrane potentials in electrotaxis and chemotaxis of
      dictyostelium cells.
AB  - Many types of cells migrate directionally in direct current (DC) electric fields
      (EFs), a phenomenon termed galvanotaxis or electrotaxis. The directional sensing
      mechanisms responsible for this response to EFs, however, remain unknown.
      Exposing cells to an EF causes changes in plasma membrane potentials (V(m)).
      Exploiting the ability of Dictyostelium cells to tolerate drastic V(m) changes,
      we investigated the role of V(m) in electrotaxis and, in parallel, in chemotaxis.
      We used three independent factors to control V(m): extracellular pH,
      extracellular [K(+)], and electroporation. Changes in V(m) were monitored with
      microelectrode recording techniques. Depolarized V(m) was observed under acidic
      (pH 5.0) and alkaline (pH 9.0) conditions as well as under higher extracellular
      [K(+)] conditions. Electroporation permeabilized the cell membrane and
      significantly reduced the V(m), which gradually recovered over 40 min. We then
      recorded the electrotactic behaviors of Dictyostelium cells with a defined V(m)
      using these three techniques. The directionality (directedness of electrotaxis)
      was quantified and compared to that of chemotaxis (chemotactic index). We found
      that a reduced V(m) significantly impaired electrotaxis without significantly
      affecting random motility or chemotaxis. We conclude that extracellular pH,
      [K(+)], and electroporation all significantly affected electrotaxis, which
      appeared to be mediated by the changes in V(m). The initial directional sensing
      mechanisms for electrotaxis therefore differ from those of chemotaxis and may be
      mediated by changes in resting V(m).

PMID- 21743004
TI  - PolyA-specific ribonuclease (PARN-1) function in stage-specific mRNA turnover in
      Trypanosoma brucei.
AB  - Deadenylation is often the rate-limiting event in regulating the turnover of
      cellular mRNAs in eukaryotes. Removal of the poly(A) tail initiates mRNA
      degradation by one of several decay pathways, including deadenylation-dependent
      decapping, followed by 5' to 3' exonuclease decay or 3' to 5' exosome-mediated
      decay. In trypanosomatids, mRNA degradation is important in controlling the
      expression of differentially expressed genes. Genomic annotation studies have
      revealed several potential deadenylases. Poly(A)-specific RNase (PARN) is a key
      deadenylase involved in regulating gene expression in mammals, Xenopus oocytes,
      and higher plants. Trypanosomatids possess three different PARN genes, PARN-1, 
      2, and -3, each of which is expressed at the mRNA level in two life-cycle stages
      of the human parasite Trypanosoma brucei. Here we show that T. brucei PARN-1 is
      an active deadenylase. To determine the role of PARN-1 on mRNA stability in vivo,
      we overexpressed this protein and analyzed perturbations in mRNA steady-state
      levels as well as mRNA half-life. Interestingly, a subset of mRNAs was affected,
      including a family of mRNAs that encode stage-specific coat proteins. These data
      suggest that PARN-1 functions in stage-specific protein production.

PMID- 21743005
TI  - Admission, discharge, or change in B-type natriuretic peptide and long-term
      outcomes: data from Organized Program to Initiate Lifesaving Treatment in
      Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) has been associated with short- and
      long-term postdischarge prognosis among hospitalized patients with heart failure.
      It is unknown if admission, discharge, or change from admission to discharge BNP
      measure is the most important predictor of long-term outcomes. METHODS AND
      RESULTS: We linked patients >=65 years of age from hospitals in Organized Program
      to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure
      (OPTIMIZE-HF) to Medicare claims. Among patients with recorded admission and
      discharge BNP, we compared Cox models predicting 1-year mortality and/or
      rehospitalization, including clinical variables and clinical variables plus BNP.
      We calculated the net reclassification improvement (NRI) and integrated
      discrimination improvement (IDI) for the best-fit model for each outcome versus
      the model with clinical variables alone. Among 7039 patients in 220 hospitals,
      median (25th, 75th) admission and discharge BNP were 832 pg/mL (451, 1660) and
      534 pg/mL (281, 1111). Observed 1-year mortality and 1-year mortality or
      rehospitalization rates were 35.2% and 79.4%. The discharge BNP model had the
      best performance and was the most important characteristic for predicting 1-year
      mortality (hazard ratio for log transformation, 1.34; 95% confidence interval,
      1.28 to 1.40) and 1-year death or rehospitalization (hazard ratio, 1.15; 95%
      confidence interval, 1.12 to 1.18). Compared with a clinical variables only
      model, the discharge BNP model improved risk reclassification and discrimination
      in predicting each outcome (1-year mortality: NRI, 5.5%, P<0.0001; IDI, 0.023,
      P<0.0001; 1-year mortality or rehospitalization: NRI, 4.2%, P<0.0001; IDI, 0.010,
      P<0.0001). CONCLUSIONS: Discharge BNP best predicts 1-year mortality and/or
      rehospitalization among older patients hospitalized with heart failure. Discharge
      BNP plus clinical variables modestly improves risk classification and model
      discrimination for long-term outcomes.

PMID- 21743006
TI  - The effect of photo-oxidative stress and inflammatory cytokine on complement
      factor H expression in retinal pigment epithelial cells.
AB  - PURPOSE: Genetic variation in complement factor H (CFH) has been implicated as a
      major risk factor for age-related macular degeneration (AMD). The reduction in
      CFH amount or its complement-modulating activity may lead to inadequate control
      of complement-driven inflammation at the outer retina. We explored the effect of
      photo-oxidative stress and inflammatory cytokine on the expression of CFH in
      retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were
      exposed to blue light in the presence of interferon-gamma (IFN-gamma). CFH
      expression in cell lysate was examined by Western blot and the secretory CFH in
      culture medium was analyzed by ELISA. RPE cells were treated with vitamin C and
      exogenous superoxide dismutase mimetic (Tempol) before photo-oxidative
      treatments. The intracellular reactive oxygen species were examined by flow
      cytometry. RESULTS: IFN-gamma increased CFH expression in RPE and the expression
      was suppressed significantly under concomitant blue light illumination. The
      secretory CFH level also decreased significantly under blue light illumination,
      which was related to the decreased intracellular mRNA and protein expressions of
      CFH. The suppression was mediated through an oxidative mechanism, and was
      particularly related to superoxide anion generation. The suppression of CFH
      expression in RPE under blue light illumination was abrogated by vitamin C and
      Tempol. CONCLUSIONS: Photo-oxidative stress reduces the ability of IFN-gamma to
      increase CFH expression in RPE. Apart from reducing the oxidative damage, vitamin
      C reduces the suppression of CFH under photo-oxidative stress. These results
      suggest a new perspective of the interaction between oxidative stress and
      inflammation, and provide a potential novel treatment strategy for age-related
      macular degeneration.

PMID- 21743007
TI  - Spry1 and Spry2 are necessary for lens vesicle separation and corneal
      differentiation.
AB  - PURPOSE: The studies reported here were performed to analyze the roles of
      Sproutys (Sprys), downstream targets and negative feedback regulators of the
      fibroblast growth factor (FGF) signaling pathway, in lens and corneal
      differentiation. METHODS: Spry1 and -2 were conditionally deleted in the lens and
      corneal epithelial precursors using the Le-Cre transgene and floxed alleles of
      Spry1 and -2. Alterations in lens and corneal development were assessed by
      hematoxylin and eosin staining, in situ hybridization, and immunohistochemistry.
      RESULTS: Spry1 and -2 were upregulated in the lens fibers at the onset of fiber
      differentiation. FGF signaling was both necessary and sufficient for induction of
      Spry1 and -2 in the lens fiber cells. Spry1 and -2 single- or double-null lenses
      failed to separate from the overlying ectoderm and showed persistent
      keratolenticular stalks. Apoptosis of stalk cells, normally seen during lens
      vesicle detachment from the ectoderm, was inhibited in Spry mutant lenses, with
      concomitant ERK activation. Prox1 and p57(KIP2), normally upregulated at the
      onset of fiber differentiation were prematurely induced in the Spry mutant lens
      epithelial cells. However, terminal differentiation markers such as beta- or
      gamma-crystallin were not induced. Corneal epithelial precursors in Spry1 and -2
      double mutants showed increased proliferation with elevated expression of Erm and
      DUSP6 and decreased expression of the corneal differentiation marker K12.
      CONCLUSIONS: Collectively, the results indicate that Spry1 and -2 (1) through
      negative modulation of ERKs allow lens vesicle separation, (2) are targets of FGF
      signaling in the lens during initiation of fiber differentiation and (3) function
      redundantly in the corneal epithelial cells to suppress proliferation.

PMID- 21743008
TI  - Toward a clinical protocol for assessing rod, cone, and melanopsin contributions
      to the human pupil response.
AB  - PURPOSE. To better understand the relative contributions of rod, cone, and
      melanopsin to the human pupillary light reflex (PLR) and to determine the optimal
      conditions for assessing the health of the rod, cone, and melanopsin pathways
      with a relatively brief clinical protocol. METHODS. PLR was measured with an eye
      tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5
      log cd/m(2) red (640 +/- 10 nm) and blue (467 +/- 17 nm) stimuli of various
      durations were presented after dark adaptation. In experiments 2 and 3, 1-second
      red and blue stimuli were presented at different intensity levels in the dark
      (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on
      the results of experiments 1 to 3, a clinical protocol was designed and tested on
      healthy control subjects and patients with retinitis pigmentosa and Leber's
      congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin
      driven sustained pupil response after termination of an intense blue stimulus was
      1 second. PLR rod- and melanopsin-driven components are best studied with low-
      and high-intensity flashes, respectively, presented in the dark (experiment 2). A
      blue background suppressed rod and melanopsin responses, making it easy to assess
      the cone contribution with a red flash (experiment 3). With the clinical
      protocol, robust melanopsin responses could be seen in patients with few or no
      contributions from the rods and cones. CONCLUSIONS. It is possible to assess the
      rod, cone, and melanopsin contributions to the PLR with blue flashes at two or
      three intensity levels in the dark and one red flash on a blue background.

PMID- 21743009
TI  - Increased integration of transplanted CD73-positive photoreceptor precursors into
      adult mouse retina.
AB  - PURPOSE. Retinal degeneration initiated by loss of photoreceptors is the
      prevalent cause of visual impairment and blindness in industrialized countries.
      Transplantation of photoreceptor cells represents a possible replacement
      strategy. This study determined that identification of cell surface antigens can
      assist in enriching photoreceptor precursors for transplantation. METHODS. The
      expression profile of rod photoreceptors at postnatal day 4 was investigated by
      microarray analysis to identify photoreceptor-specific cell surface antigens. For
      enrichment of transplantable photoreceptors, neonatal retinas from rod
      photoreceptor-specific reporter mice were dissociated, and the rods were purified
      by magnetic associated cell sorting (MACS) with CD73 antibodies. MAC-sorted cell
      fractions were transplanted into the subretinal space of adult wild-type mice.
      The number of rod photoreceptors contained in unsorted, CD73-negative, and CD73
      positive cell fractions were quantified in vitro and after grafting in vivo.
      RESULTS. Microarray analysis revealed that CD73 is a marker for rod
      photoreceptors. CD73-based MACS resulted in enrichment of rods to 87%.
      Furthermore, in comparison with unsorted cell fractions, CD73-positive MAC-sorted
      cells showed an approximately three-fold increase in the number of integrated,
      outer segment-forming photoreceptors after transplantation. CONCLUSIONS. CD73
      based MACS is a reliable method for the enrichment of integrating photoreceptors.
      Purification via cell surface markers represents a new tool for the separation of
      transplantable photoreceptor precursors from a heterogeneous cell population,
      avoiding the need of reporter gene expression in target cells.

PMID- 21743010
TI  - Responses of medial rectus motoneurons in monkeys with strabismus.
AB  - PURPOSE: Monkeys reared under conditions of alternating monocular occlusion
      during their first few months of life show large horizontal strabismus, "A"
      patterns, and dissociated vertical deviation. "A" patterns manifest as an
      inappropriate horizontal component in the deviated eye during vertical eye
      movements (cross-axis movement). The objective of this study was to investigate
      response properties of medial rectus motoneurons (MRMNs) in relation to
      strabismus properties. METHODS: Burst-tonic activity of 21 MRMNs in the
      oculomotor nucleus were recorded from two monkeys with exotropia as they
      performed horizontal and vertical smooth pursuit (0.2 Hz, +/-10 degrees ) under
      monocular viewing conditions. Neuronal responses and horizontal component of eye
      movements were used to identify regression coefficients in a first-order model
      for each tracking condition. RESULTS: Comparison of position, velocity, and
      constant parameter coefficients, estimated from horizontal tracking data with
      either eye viewing, showed no significant differences (P > 0.07), indicating that
      neuronal activity could account for the horizontal misalignment. Comparison of
      the position, velocity, and constant parameter coefficients estimated from
      horizontal tracking and the cross-axis condition showed no significant
      differences (P > 0.07), suggesting that motoneuron activity could account for
      most of the inappropriate horizontal cross-axis movement observed in the covered
      eye during vertical smooth pursuit. CONCLUSIONS: These data suggest that, in
      animals with sensory-induced strabismus, central innervation to extraocular
      muscles is responsible for setting the state of strabismus. Mechanical factors
      such as muscle length adaptation (for horizontal misalignment) and pulley
      heterotopy or static torsion (for "A" patterns) likely do not play a major role
      in determining properties in a sensory-induced strabismus.

PMID- 21743011
TI  - Frizzled 4 is required for retinal angiogenesis and maintenance of the blood
      retina barrier.
AB  - PURPOSE. Mice deficient in the secreted protein Norrin or its receptor Frizzled-4
      (FZD4) exhibit incomplete vascularization of the neural retina. However, because
      of early retinal vascular defects in the knockout models, it has not been
      possible to study FZD4 contribution in ocular neovascular disease. To further
      understand the role of this signaling pathway in physiological and pathologic
      angiogenesis, the authors generated a monoclonal antibody that neutralizes FZD4
      function in vivo. METHODS. Antibodies were generated by immunizing Fzd4 knockout
      mice with the cysteine-rich domain of FZD4. A monoclonal antibody (1.99.25) was
      discovered that antagonizes Norrin- and WNT3A-induced beta-catenin accumulation
      in vitro. 1.99.25 and an isotype-matched negative control antibody were evaluated
      in models of developmental retinal angiogenesis, oxygen-induced retinopathy, and
      retinal angiomatous proliferation. The authors also investigated the role of FZD4
      in maintaining the blood-retina barrier in normal adult mice. RESULTS.
      Administration of 1.99.25 inhibited physiological and pathologic sprouting
      angiogenesis within the retina. Inhibition of FZD4 in developing retinal vascular
      networks caused the upregulation of PLVAP, a protein normally associated with
      fenestrated, immature endothelium in the CNS. In the adult neural retina, the
      administration of 1.99.25 induced PLVAP expression in the deep capillary bed and
      enabled extravasation of small and large molecules through the blood-retina
      barrier. CONCLUSIONS. These results demonstrate that FZD4 is required for
      physiological and pathologic angiogenesis in the retina and for regulation of
      retinal endothelial cell differentiation. The authors also show that FZD4 is
      critical for maintaining the integrity of the mature blood-retina barrier.

PMID- 21743012
TI  - Chronic implantation of newly developed suprachoroidal-transretinal stimulation
      prosthesis in dogs.
AB  - PURPOSE: To investigate the feasibility of implanting a newly developed
      suprachoroidal-transretinal stimulation (STS) prosthesis in dogs and to determine
      its biocompatibility and stability over a 3-month period. METHODS: The STS
      prosthesis system consisted of an array of 49 electrodes (nine were active), an
      intravitreal return electrode, and an extraocular microstimulator. The 49
      electrode array was implanted into a scleral pocket of each of three healthy
      beagle dogs. Color fundus photography, fluorescein angiography,
      electroretinography, and functional testing of the STS system were performed
      postoperatively. The dogs were euthanatized 3 months after the implantation, and
      the retinas were evaluated histologically. RESULTS: All the prostheses were
      successfully implanted without complications, and no serious complications
      occurred during the 3-month postoperative period. The fixation of the implant was
      stable throughout the experimental period. Fluorescein angiography showed that
      the entire retina, including the area on the electrode array, remained well
      perfused without intraocular inflammation. Electroretinograms recorded from the
      eyes with the prosthesis did not differ significantly from those recorded from
      control eyes. Functional testing of the STS system showed that this system
      performed well for the 3-month experimental period. Histologic evaluations showed
      good preservation of the retina over the electrode array. CONCLUSIONS:
      Implantation of a newly developed STS retinal prosthesis into a scleral pocket of
      beagle dogs is surgically feasible and can be performed without significant
      damage to the retina or the animal. The biocompatibility and stability of the
      system were good for the 3-month observation period.

PMID- 21743013
TI  - Heparan sulfate regulates intraretinal axon pathfinding by retinal ganglion
      cells.
AB  - PURPOSE. Heparan sulfate (HS) is abundantly expressed in the developing neural
      retina; however, its role in the intraretinal axon guidance of retinal ganglion
      cells (RGCs) remains unclear. In this study, the authors examined whether HS was
      essential for the axon guidance of RGCs toward the optic nerve head. METHODS. The
      authors conditionally ablated the gene encoding the exostosin-1 (Ext1) enzyme,
      using the dickkopf homolog 3 (Dkk3)-Cre transgene, which disrupted HS expression
      in the mouse retina during directed pathfinding by RGC axons toward the optic
      nerve head. In situ hybridization, immunohistochemistry, DiI tracing, binding
      assay, and retinal explant assays were performed to evaluate the phenotypes of
      the mutants and the roles of HS in intraretinal axon guidance. RESULTS. Despite
      no gross abnormality in RGC distribution, the mutant RGC axons exhibited severe
      intraretinal guidance errors, including optic nerve hypoplasia, ectopic axon
      penetration through the full thickness of the neural retina and into the
      subretinal space, and disturbance of the centrifugal projection of RGC axons
      toward the optic nerve head. These abnormal phenotypes shared similarities with
      the RGC axon misguidance caused by mutations of genes encoding Netrin-1 and Slit
      1/2. Explant assays revealed that the mutant RGCs exhibited disturbed Netrin-1
      dependent axon outgrowth and Slit-2-dependent repulsion. CONCLUSIONS. The present
      study demonstrated that RGC axon projection toward the optic nerve head requires
      the expression of HS in the neural retina, suggesting that HS in the retina
      functions as an essential modulator of Netrin-1 and Slit-mediated intraretinal
      RGC axon guidance.

PMID- 21743014
TI  - Induction of differentiation by pyruvate and DMEM in the human retinal pigment
      epithelium cell line ARPE-19.
AB  - PURPOSE: Cultured retinal pigment epithelium (RPE) may become a therapeutic
      option for transplantation in retinal disease. However maintaining a native RPE
      phenotype in vitro has proven challenging. The human RPE cell-line ARPE-19 is
      used widely as an alternative to primary RPE. It is grown in DMEM/F12 medium as
      standard, but its phenotype is dependent on culture conditions, and many
      differentiation markers are usually absent. The purpose of this study was to
      examine how this sensitive phenotype of ARPE-19 can be modulated by growth media
      with or without the metabolite pyruvate to elucidate better RPE growth
      conditions. METHODS: ARPE-19 cells at passages p22 to p28 were cultured on
      filters for up to 3 months in DMEM/F12 or DMEM media with or without pyruvate and
      1% fetal calf serum. Assessment of differentiation was performed using
      pigmentation, immunocytochemistry, protein/mRNA expression, transepithelial
      resistance, VEGF secretion, and ultrastructure. RESULTS: Pyruvate, in combination
      with DMEM, induced dark pigmentation and promoted differentiation markers such as
      CRALBP and MerTK. Importantly, RPE65 protein was detected by Western blotting and
      was enhanced by pyruvate, high glucose, and DMEM. ARPE-19 cells maintained in
      this medium could also phagocytose human photoreceptor outer segments (POS). VEGF
      secretion was greater in DMEM cultures and was affected by glucose but not by
      pyruvate. Pigmentation never occurred in DMEM/F12. CONCLUSIONS: This study
      demonstrated important differentiation markers, including pigmentation and
      Western blots of RPE65 protein, and showed human POS phagocytosis in ARPE-19
      cultures using a simple differentiation protocol. The results favor the use of
      high-glucose DMEM with pyruvate for future RPE differentiation studies.

PMID- 21743015
TI  - Large proteoglycan complexes and disturbed collagen architecture in the corneal
      extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome).
AB  - PURPOSE: Deficiencies in enzymes involved in proteoglycan (PG) turnover underlie
      a number of rare mucopolysaccharidoses (MPS), investigations of which can
      considerably aid understanding of the roles of PGs in corneal matrix biology.
      Here, the authors analyze novel pathologic changes in MPS VII (Sly syndrome) to
      determine the nature of PG-collagen associations in stromal ultrastructure.
      METHODS: Transmission electron microscopy and electron tomography were used to
      investigate PG-collagen architectures and interactions in a cornea obtained at
      keratoplasty from a 22-year-old man with MPS VII, which was caused by a compound
      heterozygous mutation in the GUSB gene. RESULTS: Transmission electron microscopy
      showed atypical morphology of the epithelial basement membrane and Bowman's layer
      in MPS VII. Keratocytes were packed with cytoplasmic vacuoles containing abnormal
      glycosaminoglycan (GAG) material, and collagen fibrils were thinner than in
      normal cornea and varied considerably throughout anterior (14-32 nm), mid (13-42
      nm), and posterior (17-39 nm) regions of the MPS VII stroma. PGs viewed in three
      dimensions were striking in appearance in that they were significantly larger
      than PGs in normal cornea and formed highly extended linkages with multiple
      collagen fibrils. CONCLUSIONS: Cellular changes in the MPS VII cornea resemble
      those in other MPS. However, the wide range of collagen fibril diameters
      throughout the stroma and the extensive matrix presence of supranormal-sized PG
      structures appear to be unique features of this disorder. The findings suggest
      that the accumulation of stromal chondroitin-, dermatan-, and heparan-sulfate
      glycosaminoglycans in the absence of beta-glucuronidase-mediated degradation can
      modulate collagen fibrillogenesis.

PMID- 21743016
TI  - Macular measurements using optical coherence tomography in healthy Chinese school
      age children.
AB  - PURPOSE: To evaluate macular thickness/volume in a Chinese population of primary
      school children using optical coherence tomography (OCT), and assess its
      association with age, sex, spherical equivalent refraction (SE), body mass index
      (BMI), and intraocular pressure (IOP). METHODS: Healthy Chinese children (n =
      806) from six randomly selected primary schools in Chongming County, Shanghai,
      China, were enrolled. Comprehensive standardized ophthalmic examinations included
      visual acuity, cycloplegic refraction, IOP, and fast macular scans using Stratus
      OCT. Mean values for the nine Early Treatment Diabetic Retinopathy Study (ETDRS)
      areas, foveal minimum thickness, and macular volume were calculated. RESULTS: OCT
      data from right eyes with high-quality scans were evaluated in 720 children
      (89.3% of total participants; 46.5% boys). Macular thickness and volume were
      normally distributed. The mean foveal minimum thickness was 140.0 +/- 12.3 MUm.
      There were significant differences between the boys and the girls in mean foveal
      volume (P = 0.023) and sectoral macular thickness in all the quadrants of the
      inner ring (P < 0.001 and P = 0.001) and temporal outer quadrant (P = 0.009). SE
      refraction correlated positively with inner and outer macular thickness and total
      macular volume (P < 0.001) and negatively with central macular volume (P =
      0.012). BMI correlated significantly only with outer macular thickness (r =
      0.074, P = 0.048). No age- and IOP-related differences were found in the macular
      parameters. CONCLUSIONS: OCT demonstrated that macular thickness/volume was
      normally distributed in this sample of Chinese children, with variations in sex
      and SE. The variables in macular thickness/volume should be considered when
      diagnosing and monitoring school-aged children with diseases that affect the
      macula.

PMID- 21743017
TI  - Prediction, by retinal location, of the onset of diabetic edema in patients with
      nonproliferative diabetic retinopathy.
AB  - PURPOSE: To formulate a model to predict the location of the onset of diabetic
      retinal edema (DE) in adults with diabetic retinopathy (DR), at risk for DE.
      METHODS: In all, 46 eyes from 23 patients with DR were included. Subjects were
      followed semiannually until DE developed or the study concluded. The presence or
      absence of DE within the central 45  degrees  at the final visit was the outcome
      measure, and data from the prior visit were used as baseline. A logistic
      regression model was formulated to assess the relationship between DE development
      and: multifocal electroretinogram (mfERG) implicit time (IT) Z-score, mfERG
      amplitude (Amp) Z-score, sex, diabetes duration, diabetes type, blood glucose,
      HbA1c, age, systolic (SBP) and diastolic blood pressure, and grade of
      retinopathy. A total of 35 retinal zones were constructed from the mfERG elements
      and each was graded for DE. Data from 52 control subjects were used to calculate
      the maximum IT and minimum Amp Z-scores for each zone. Receiver operating
      characteristic curves from a fivefold cross-validation were used to determine the
      model's predictive properties. RESULTS: Edema developed in 5.2% of all retinal
      zones and in 35% of the eyes. The mfERG Amp, mfERG IT, SBP, and sex were together
      predictive of edema onset. Combined, these factors produce a model that has 84%
      sensitivity and 76% specificity. CONCLUSIONS: Together mfERG, SBP, and sex are
      good predictors of local edema in patients with DR. The model is a useful tool
      for assessing risk for edema development and a candidate measure to evaluate
      novel therapeutics directed at DE.

PMID- 21743018
TI  - Expression profile of the matricellular protein osteopontin in primary open-angle
      glaucoma and the normal human eye.
AB  - PURPOSE. To characterize the role of osteopontin (OPN) in primary open-angle
      glaucoma (POAG) and normal eyes. METHODS. OPN quantification was performed by
      enzyme-linked immunosorbent assay in aqueous humor (AH) obtained from human donor
      eyes (POAG and normal) and surgical samples (POAG and elective cataract removal).
      OPN expression and localization in whole eye tissue sections and primary normal
      human trabecular meshwork (NTM) cells were studied by Western blot and
      immunohistochemistry. Latanoprost-free acid (LFA)-treated NTM cells were analyzed
      for OPN gene and protein expression. Intraocular pressure was measured by
      tonometry, and central corneal thickness was measured by optical coherence
      tomography in young OPN(-/-) and wild-type mice. RESULTS. OPN levels were
      significantly reduced in donor POAG AH compared with normal AH (0.54 +/- 0.18
      ng/MUg [n = 8] vs. 0.77 +/- 0.23 ng/MUg [n = 9]; P = 0.039). A similar trend was
      observed in surgical AH (1.05 +/- 0.31 ng/MUg [n = 20] vs. 1.43 +/- 0.88 ng/MUg
      [n = 20]; P = 0.083). OPN was present in the trabecular meshwork, corneal
      epithelium and endothelium, iris, ciliary body, retina, vitreous humor, and optic
      nerve. LFA increased OPN gene expression, but minimal change in OPN protein
      expression was observed. No difference in intraocular pressure (17.5 +/- 2.0 mm
      Hg [n = 56] vs. 17.3 +/- 1.9 mm Hg [n = 68]) but thinner central corneal
      thickness (91.7 +/- 3.6 MUm [n = 50] vs. 99.2 +/- 5.5 MUm [n = 70]) was noted
      between OPN(-/-) and wild-type mice. CONCLUSIONS. OPN is widely distributed in
      the human eye and was found in lower concentrations in POAG AH. Reduction of OPN
      in young mice does not affect IOP.

PMID- 21743019
TI  - Evaluation of proteoglycan gene polymorphisms as risk factors in the genetic
      susceptibility to high myopia.
AB  - PURPOSE. To investigate the relationship between high myopia and single
      nucleotide polymorphisms (SNPs) in six proteoglycan genes: aggrecan (ACAN),
      fibromodulin (FMOD), decorin (DCN), lumican (LUM), keratocan (KERA), and
      epiphycan (EPYC). These genes were selected for study because they are involved
      in induced myopia in animals and/or are within the human MYP3 locus identified by
      linkage analysis of families with high myopia. METHODS. Two groups of Chinese
      subjects were studied: group 1 (300 cases and 300 controls) and group 2 (356
      cases and 354 controls). Cases were high myopes with spherical equivalent (SE) <=
      -8.00 D, and controls had SE between +1.0 and -1.0 D. From these candidate genes,
      60 tagging SNPs were selected. First, 12 DNA pools were each constructed from 50
      samples of the same phenotype from group 1 subjects and were tested for
      association with the SNPs. Second, putatively positive SNPs were confirmed by
      individual genotyping of group 1 subjects. Finally, positive results were
      replicated in group 2 subjects. RESULTS. Of the 58 SNPs successfully screened by
      DNA pooling, 8 ACAN SNPs passed the threshold of P <= 0.10 (nested ANOVA) and
      were then genotyped in the individual samples. Haplotypes rs3784757 and rs1516794
      showed significant association with high myopia. However, the positive result
      could not be replicated in the second subject group. CONCLUSIONS. These six
      proteoglycan genes were not associated with high myopia in these Chinese subjects
      and hence are unlikely to be important in the genetic predisposition to high
      myopia.

PMID- 21743020
TI  - Efficacy of pig-to-rhesus lamellar corneal xenotransplantation.
AB  - PURPOSE. To solve the shortage of donor corneas, a decellularizing method based
      on hypertonic saline treatment was introduced, and a favorable outcome was
      observed in pig-to-rabbit lamellar corneal transplantation. This study was an
      investigation of the efficacy of pig-to-nonhuman primate lamellar corneal
      transplantation, using both decellularized and fresh porcine corneas to assess
      feasibility as a substitute for human corneas. METHODS. Nine Chinese rhesus
      macaques underwent lamellar corneal transplantation using both decellularized (n
      = 5) and fresh (n = 4) porcine corneas. Clinically acceptable graft size (7.5 mm
      in diameter) and minimal immunosuppression based on topical and systemic
      corticosteroids were applied. Rejection signs, histology of porcine grafts, and
      serial changes in recipients' blood profile, including memory T-cell subset, anti
      alpha-Gal and donor pig-specific antibodies, and complement were evaluated.
      Changes in aqueous complement concentration were also assessed at 4 weeks after
      transplantation. RESULTS. Of the decellularized porcine lamellar grafts, 80%
      remained transparent for more than 6 months, whereas half of the fresh porcine
      lamellar grafts developed chronic rejection. Rejected grafts showed extensive
      cellular infiltration, predominantly CD8(+) T lymphocytes and macrophages.
      Immunologic profiles of the recipients with rejected grafts showed a significant
      increase in the concentration of aqueous complement, an enhancement of memory T
      cells, and an abrupt increase in donor pig-specific antibodies. CONCLUSIONS. The
      findings suggested that decellularized porcine cornea could be a promising
      substitute for human corneal allograft. Fresh porcine cornea may be a feasible
      option for a substitute if combined with more potent immunosuppression or if
      obtained from transgenic pigs with complement-regulatory proteins.

PMID- 21743021
TI  - ATP-sensitive potassium (KATP) channel activation decreases intraocular pressure
      in the anterior chamber of the eye.
AB  - PURPOSE. ATP-sensitive potassium channel (K(ATP)) openers target key cellular
      events, many of which have been implicated in glaucoma. The authors sought to
      determine whether K(ATP) channel openers influence outflow facility in human
      anterior segment culture and intraocular pressure (IOP) in vivo. METHODS.
      Anterior segments from human eyes were placed in perfusion organ culture and
      treated with the K(ATP) channel openers diazoxide, nicorandil, and P1075 or the
      K(ATP) channel closer glyburide (glibenclamide). The presence, functionality, and
      specificity of K(ATP) channels were determined by RT-PCR, immunohistochemistry,
      and inside-out patch clamp in human trabecular meshwork (TM) tissue or primary
      cultures of normal human trabecular meshwork (NTM) cells. The effect of diazoxide
      on IOP in anesthetized Brown Norway rats was measured with a rebound tonometer.
      RESULTS. K(ATP) channel openers increased outflow facility in human anterior
      segments (0.14 +/- 0.02 to 0.26 +/- 0.09 MUL/min/mm Hg; P < 0.001) compared with
      fellow control eyes (0.22 +/- 0.11 to 0.21 +/- 0.11 MUL/min/mm Hg; P > 0.5). The
      effect was reversible, with outflow facility returning to baseline after drug
      removal. The addition of glyburide inhibited diazoxide from increasing outflow
      facility. Electrophysiology confirmed the presence and specificity of functional
      K(ATP) channels. K(ATP) channel subunits K(ir)6.1, K(ir)6.2, SUR2A, and SUR2B
      were expressed in TM and NTM cells. In vivo, diazoxide significantly lowered IOP
      in Brown Norway rats. CONCLUSIONS. Functional K(ATP) channels are present in the
      trabecular meshwork. When activated by K(ATP) channel openers, these channels
      increase outflow facility through the trabecular outflow pathway in human
      anterior segment organ culture and decrease IOP in Brown Norway rat eyes.

PMID- 21743022
TI  - Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Aromatase inhibitors are associated with consistent improvements in
      disease-free survival but not in overall survival. We conducted a literature
      based meta-analysis of randomized trials to examine whether the relative toxicity
      of aromatase inhibitors compared with tamoxifen may explain this finding.
      METHODS: We conducted a systematic review to identify randomized controlled
      trials that compared aromatase inhibitors and tamoxifen as primary adjuvant
      endocrine therapy in postmenopausal women by searching MEDLINE, EMBASE, and
      databases of the American Society of Clinical Oncology and San Antonio Breast
      Cancer Symposium. Odds ratios (ORs), 95% confidence intervals (CIs), absolute
      risks, and the number needed to harm associated with one adverse event were
      computed for prespecified serious adverse events including cardiovascular
      disease, cerebrovascular disease, bone fractures, thromboembolic events,
      endometrial carcinoma and other second cancers not including new breast cancer.
      All statistical tests were two-sided. RESULTS: Seven trials enrolling 30,023
      patients met the inclusion criteria. Longer duration of aromatase inhibitor use
      was associated with increased odds of developing cardiovascular disease (OR =
      1.26, 95% CI = 1.10 to 1.43, P < .001; number needed to harm = 132) and bone
      fractures (OR = 1.47, 95% CI = 1.34 to 1.61, P < .001; number needed to harm =
      46), but a decreased odds of venous thrombosis (OR = 0.55, 95% CI = 0.46 to 0.64,
      P < .001; number needed to harm = 79) and endometrial carcinoma (OR = 0.34, 95%
      CI = 0.22 to 0.53, P < .001; number needed to harm = 258). Five years of
      aromatase inhibitors was associated with a non-statistically significant
      increased odds of death without recurrence compared with 5 years of tamoxifen
      alone or tamoxifen for 2-3 years followed by an aromatase inhibitor for 2-3 years
      (OR = 1.11, 95% CI = 0.98 to 1.26, P = .09). CONCLUSIONS: The cumulative toxicity
      of aromatase inhibitors when used as up-front treatment may explain the lack of
      overall survival benefit despite improvements in disease-free survival. Switching
      from tamoxifen to aromatase inhibitors reduces this toxicity and is likely the
      best balance between efficacy and toxicity.

PMID- 21743023
TI  - Modulation of pancreatic cancer chemoresistance by inhibition of TAK1.
AB  - BACKGROUND: TGF-beta-activated kinase-1 (TAK1), a mitogen-activated protein
      kinase kinase kinase, functions in the activation of nuclear factor kappaB (NF
      kappaB) and activator protein-1, which can suppress proapoptotic signaling
      pathways and thus promote resistance to chemotherapeutic drugs. However, it is
      not known if inhibition of TAK1 is effective in reducing chemoresistance to
      therapeutic drugs against pancreatic cancer. METHODS: NF-kappaB activity was
      measured by luciferase reporter assay in human pancreatic cancer cell lines AsPc
      1, PANC-1, and MDAPanc-28, in which TAK1 expression was silenced by small hairpin
      RNA. TAK1 kinase activity was targeted in AsPc-1, PANC-1, MDAPanc-28, and
      Colo357FG cells with exposure to increasing doses of a selective small-molecule
      inhibitor, LYTAK1, for 24 hours. To test the effect of LYTAK1 in combination with
      chemotherapeutic agents, AsPc-1, PANC-1, MDAPanc-28 cells, and control cells were
      treated with increasing doses of oxaliplatin, SN-38, or gemcitabine in
      combination with LYTAK1. In vivo activity of oral LYTAK1 was evaluated in an
      orthotopic nude mouse model (n = 40, 5 per group) with luciferase-expressing AsPc
      1 pancreatic cancer cells. The results of in vitro proliferation were analyzed
      for statistical significance of differences by nonlinear regression analysis;
      differences in mouse survival were determined using a log-rank test. All
      statistical tests were two-sided. RESULTS: AsPc-1 and MDAPanc-28 TAK1 knockdown
      cells had a statistically significantly lower NF-kappaB activity than did their
      respective control cell lines (relative luciferase activity: AsPc-1, mean = 0.18,
      95% confidence interval [CI] = 0.10 to 0.27; control, mean = 3.06, 95% CI = 2.31
      to 3.80; MDAPanc-28, mean = 0.30, 95% CI = 0.13 to 0.46; control, mean = 4.53,
      95% CI = 3.43 to 5.63; both P < .001). TAK1 inhibitor LYTAK1 had potent in vitro
      cytotoxic activity in AsPc-1, PANC-1, MDAPanc-28, and Colo357FG cells, with
      IC(50) between 5 and 40 nM. LYTAK1 also potentiated the cytotoxicity of
      chemotherapeutic agents oxaliplatin, SN-38, and gemcitabine in AsPc-1, PANC-1,
      and MDAPanc-28 cells compared with control cells (P < .001). In nude mice, oral
      administration of LYTAK1 plus gemcitabine statistically significantly reduced
      tumor burden (gemcitabine vs gemcitabine plus LYTAK1, P = .03) and prolonged
      survival duration (median survival: gemcitabine, 82 days vs gemcitabine plus
      LYTAK1, 122 days; hazard ratio = 0.334, 95% CI = 0.027 to 0.826, P = .029).
      CONCLUSIONS: The results of this study suggest that genetic silencing or
      inhibition of TAK1 kinase activity in vivo is a potential therapeutic approach to
      reversal of the intrinsic chemoresistance of pancreatic cancer.

PMID- 21743024
TI  - Cigarette smoke exposure aggravates air space enlargement and alveolar cell
      apoptosis in Smad3 knockout mice.
AB  - The concept of genetic susceptibility factors predisposing cigarette smokers to
      develop emphysema stems from the clinical observation that only a fraction of
      smokers develop clinically significant chronic obstructive pulmonary disease. We
      investigated whether Smad3 knockout mice, which develop spontaneous air space
      enlargement after birth because of a defect in transforming growth factor-beta
      (TGF-beta) signaling, develop enhanced alveolar cell apoptosis and air space
      enlargement following cigarette smoke exposure. We investigated Smad3(-/-) and
      Smad3(+/+) mice at different adult ages and determined air space enlargement,
      alveolar cell proliferation, and apoptosis. Furthermore, laser-capture
      microdissection and real-time PCR were used to measure compartment-specific gene
      expression. We then compared the effects of cigarette smoke exposure on Smad3(-/
      ) and littermate controls. Smad3 knockout resulted in the development of air
      space enlargement in the adult mouse and was associated with decreased alveolar
      VEGF levels and activity and increased alveolar cell apoptosis. Cigarette smoke
      exposure aggravated air space enlargement and alveolar cell apoptosis. We also
      found increased Smad2 protein expression and phosphorylation, which was enhanced
      following cigarette smoke exposure, in Smad3-knockout animals. Double
      immunofluorescence analysis revealed that endothelial apoptosis started before
      epithelial apoptosis. Our data indicate that balanced TGF-beta signaling is not
      only important for regulation of extracellular matrix turnover, but also for
      alveolar cell homeostasis. Impaired signaling via the Smad3 pathway results in
      alveolar cell apoptosis and alveolar destruction, likely via increased Smad2 and
      reduced VEGF expression and might represent a predisposition for accelerated
      development of emphysema due to cigarette smoke exposure.

PMID- 21743025
TI  - Role of the Fas/FasL system in a model of RSV infection in mechanically
      ventilated mice.
AB  - Infection with respiratory syncytial virus (RSV) in children can progress to
      respiratory distress and acute lung injury necessitating mechanical ventilation
      (MV). MV enhances apoptosis and inflammation in mice infected with pneumonia
      virus of mice (PVM), a mouse pneumovirus that has been used as a model for severe
      RSV infection in mice. We hypothesized that the Fas/Fas ligand (FasL) system, a
      dual proapoptotic/proinflammatory system involved in other forms of lung injury,
      is required for enhanced lung injury in mechanically ventilated mice infected
      with PVM. C57BL/6 mice and Fas-deficient ("lpr") mice were inoculated
      intratracheally with PVM. Seven or eight days after PVM inoculation, the mice
      were subjected to 4 h of MV (tidal volume 10 ml/kg, fraction of inspired O(2) =
      0.21, and positive end-expiratory pressure = 3 cm H(2)O). Seven days after PVM
      inoculation, exposure to MV resulted in less severe injury in lpr mice than in
      C57BL/6 mice, as evidenced by decreased numbers of polymorphonuclear neutrophils
      in the bronchoalveolar lavage (BAL), and lower concentrations of the
      proinflammatory chemokines KC, macrophage inflammatory protein (MIP)-1alpha, and
      MIP-2 in the lungs. However, when PVM infection was allowed to progress one
      additional day, all of the lpr mice (7/7) died unexpectedly between 0.5 and 3.5 h
      after the onset of ventilation compared with three of the seven ventilated
      C57BL/6 mice. Parameters of lung injury were similar in nonventilated mice, as
      was the viral content in the lungs and other organs. Thus, the Fas/FasL system
      was partly required for the lung inflammatory response in ventilated mice
      infected with PVM, but attenuation of lung inflammation did not prevent
      subsequent mortality.

PMID- 21743026
TI  - Activation of MMP-9 by human lung epithelial cells in response to the cystic
      fibrosis-associated pathogen Burkholderia cenocepacia reduced wound healing in
      vitro.
AB  - Burkholderia cepacia complex is a group of bacterial pathogens that cause
      opportunistic infections in cystic fibrosis (CF). The most virulent of these is
      Burkholderia cenocepacia. Matrix metalloproteinases (MMPs) are upregulated in CF
      patients. The aim of this work was to examine the role of MMPs in the
      pathogenesis of B. cepacia complex, which has not been explored to date. Real
      time PCR analysis showed that B. cenocepacia infection upregulated MMP-2 and MMP
      9 genes in the CF lung cell line CFBE41o- within 1 h, whereas MMP-2, -7, and -9
      genes were upregulated in the non-CF lung cell line 16HBE14o-. Conditioned media
      from both cell lines showed increased MMP-9 activation following B. cenocepacia
      infection. Conditioned media from B. cenocepacia-infected cells significantly
      reduced the rate of wound healing in confluent lung epithelia (P < 0.05), in
      contrast to conditioned media from Pseudomonas aeruginosa-infected cells, which
      showed predominant MMP-2 activation. Treatment of control conditioned media from
      both cell lines with the MMP activator 4-aminophenylmercuric acetate (APMA) also
      resulted in clear activation of MMP-9 and to a much lesser extent MMP-2. APMA
      treatment of control media also delayed the repair of wound healing in confluent
      epithelial cells. Furthermore, specific inhibition of MMP-9 in medium from cells
      exposed to B. cenocepacia completely reversed the delay in wound repair. These
      data suggest that MMP-9 plays a role in the reduced epithelial repair observed in
      response to B. cenocepacia infection and that its activation following B.
      cenocepacia infection contributes to the pathogenesis of this virulent pathogen.

PMID- 21743027
TI  - Differential flux of macrophage inflammatory protein-2 and cytokine-induced
      neutrophil chemoattractant from the lung after intrapulmonary delivery.
AB  - Previously we showed that cytokine-induced neutrophil chemoattractant (CINC), but
      not macrophage inflammatory protein-2 (MIP-2), is detected in plasma after
      intratracheal challenge with LPS or the particular chemokines. To further
      understand the differences between CINC and MIP-2 flux from the lung, we
      attempted to detect the two chemokines in isolated erythrocytes and leukocytes in
      rats after intratracheal LPS challenge. In response to intratracheal LPS, we
      found both CINC and MIP-2 in isolated erythrocytes and leukocytes, suggesting
      that MIP-2 produced in the LPS-challenged lung entered the circulation like CINC.
      To assess the relative flux of CINC and MIP-2 from the intra-alveolar compartment
      into the blood, experiments were performed in rats implanted with vascular
      catheters in which both chemokines were either injected intratracheally (5 MUg)
      or infused intravenously (20 ng/min) and subsequently measured in plasma or with
      the cellular elements. Both chemokines appeared in the blood following
      intratracheal injection, with CINC detected in plasma and cells but MIP-2 only
      detected in the cellular fraction of blood. Infusion of both chemokines allowed
      detection of MIP-2 and CINC in plasma and with the cellular elements, which
      allowed us to calculate clearance for each chemokine and to assess CINC and MIP-2
      rates of appearance (Ra) following intratracheal injection. On the basis of
      plasma and whole blood clearance, CINC Ra was more than sevenfold and fourfold
      higher, respectively, than MIP-2 Ra. This analysis indicates that differences
      exist in the rate of flux of CINC and MIP-2 across the epithelial/endothelial
      barrier of the lung, despite similar molecular size.

PMID- 21743028
TI  - Enhancement of alveolar epithelial sodium channel activity with decreased cystic
      fibrosis transmembrane conductance regulator expression in mouse lung.
AB  - We sought to establish whether the cystic fibrosis transmembrane conductance
      regulator (CFTR) regulates the activity of amiloride-sensitive sodium channels
      (ENaC) in alveolar epithelial cells of wild-type, heterozygous (Cftr(+/-)),
      knockout (Cftr(-/-)), and DeltaF508-expressing mice in situ. RT-PCR studies
      confirmed the presence of CFTR message in freshly isolated alveolar type II
      (ATII) cells from wild-type mice. We patched alveolar type I (ATI) and ATII cells
      in freshly prepared lung slices from these mice and demonstrated the presence of
      4-pS ENaC channels with the following basal open probabilities (P(o)): wild
      type=0.21 +/- 0.015: Cftr(+/-)=0.4 +/- 0.03; DeltaF508=0.55 +/- 0.01; and Cftr(-/
      )=and 0.81 +/- 0.016 (means +/- SE; n >= 9). Forskolin (5 MUM) or trypsin (2
      MUM), applied in the pipette solution, increased the P(o) and number of channels
      in ATII cells of wild-type, Cftr(+/-), and DeltaF508, but not in Cftr(-/-) mice,
      suggesting that the latter were maximally activated. Western blot analysis showed
      that lungs of all groups of mice had similar levels of alpha-ENaC; however, lungs
      of Cftr(+/-) and Cftr(-/-) mice had significantly higher levels of an alpha-ENaC
      proteolytic fragment (65 kDa) that is associated with active ENaC channels. Our
      results indicate that ENaC activity is inversely correlated to predicted CFTR
      levels and that CFTR heterozygous and homozygous mice have higher levels of
      proteolytically processed ENaC fragments in their lungs. This is the first
      demonstration of functional ENaC-CFTR interactions in alveolar epithelial cells
      in situ.

PMID- 21743029
TI  - The oncogene Trop2 regulates fetal lung cell proliferation.
AB  - The factors regulating growth of the developing lung are poorly understood,
      although the degree of fetal lung expansion is critical. The oncogene Trop2
      (trophoblast antigen 2) is upregulated during accelerated fetal lung growth, and
      we hypothesized that it may regulate normal fetal lung growth. We investigated
      Trop2 expression in the fetal and neonatal sheep lung during accelerated and
      delayed lung growth induced by alterations in fetal lung expansion, as well as in
      response to glucocorticoids. Trop2 expression was measured using real-time PCR
      and localized spatially using in situ hybridization and immunofluorescence.
      During normal lung development, Trop2 expression was higher at 90 days
      gestational age (GA; 4.0 +/- 0.8) than at 128 days GA (1.0 +/- 0.1), decreased to
      0.5 +/- 0.1 at 142 days GA (full term ~147 days GA), and was positively
      correlated to lung cell proliferation rates (r = 0.953, P < 0.005). Trop2
      expression was regulated by fetal lung expansion, but not by glucocorticoids. It
      was increased nearly threefold by 36 h of increased fetal lung expansion (P <
      0.05) and was reduced to ~55% of control levels by reduced fetal lung expansion
      (P < 0.05). Trop2 expression was associated with lung cell proliferation during
      normal and altered lung growth, and the TROP2 protein colocalized with Ki-67
      positive cells in the fetal lung. TROP2 was predominantly localized to
      fibroblasts and type II alveolar epithelial cells. Trop2 small interfering RNA
      decreased Trop2 expression by ~75% in cultured fetal rat lung fibroblasts and
      decreased their proliferation by ~50%. Cell viability was not affected. This
      study demonstrates that TROP2 regulates lung cell proliferation during
      development.

PMID- 21743030
TI  - Age and sex dimorphisms contribute to the severity of bleomycin-induced lung
      injury and fibrosis.
AB  - Fibrotic interstitial pneumonias are more prevalent in males of advancing age,
      although little is known about the underlying mechanisms. To evaluate the
      contributions of age and sex to the development of pulmonary fibrosis, we
      intratracheally instilled young (8-12 wk) and aged (52-54 wk) male and female
      mice with bleomycin and assessed the development and severity of fibrotic lung
      disease by measurements of lung collagen levels, static compliance, leukocyte
      infiltration, and stereological quantification of fibrotic areas in histological
      sections. We also quantified proinflammatory and profibrotic chemokine and
      cytokine levels in the bronchoalveolar lavage fluid. Aged male mice developed
      more severe lung disease, indicated by increased mortality, increased collagen
      deposition, and neutrophilic alveolitis compared with aged female mice or young
      mice of either sex. Aged male mice also exhibited increased levels of
      transforming growth factor-beta, IL-17A, and CXCL1 in their bronchoalveolar
      lavage fluid. Young male mice developed a more fibrotic disease after bleomycin
      instillation compared with female mice, regardless of age. There was no
      difference in fibrosis between young and aged female mice. Taken together, these
      findings suggest that the variables of advanced age and male sex contribute to
      the severity of pulmonary fibrosis in this model. Our findings also emphasize the
      importance of stratifying experimental groups on the basis of age and sex in
      experimental and epidemiological studies of this nature.

PMID- 21743031
TI  - Inflammation and matrix remodeling during repair of ventilator-induced lung
      injury.
AB  - High-pressure ventilation triggers different inflammatory and matrix remodeling
      responses within the lung. Although some of them may cause injury, the
      involvement of these mediators in repair is largely unknown. To identify
      mechanisms of repair after ventilator-induced lung injury (VILI), mice were
      randomly assigned to baseline conditions (no ventilation), injury [90 min of high
      pressure ventilation without positive end-expiratory pressure (PEEP)], repair
      (injury followed by 4 h of low-pressure ventilation with PEEP), and ventilated
      controls (low-pressure ventilation with PEEP for 90 and 330 min). Histological
      injury and lung permeability increased during injury, but were partially reverted
      in the repair group. This was accompanied by a proinflammatory response, together
      with increases in TNF-alpha and IFN-gamma, which returned to baseline during
      repair, and a decrease in IL-10. However, macrophage inflammatory protein-2 (MIP
      2) and matrix metalloproteinases (MMP)-2 and -9 increased after injury and
      persisted in being elevated during repair. Mortality in the repair phase was 50%.
      Survivors showed increased cell proliferation, lower levels of collagen, and
      higher levels of MIP-2 and MMP-2. Pan-MMP or specific MMP-2 inhibition (but not
      MIP-2, TNF-alpha, or IL-4 inhibition) delayed epithelial repair in an in vitro
      wound model using murine or human alveolar cells cultured in the presence of
      bronchoalveolar lavage fluid from mice during the repair phase or from patients
      with acute respiratory distress syndrome, respectively. Similarly, MMP inhibition
      with doxycycline impaired lung repair after VILI in vivo. In conclusion, VILI can
      be reverted by normalizing ventilation pressures. An adequate inflammatory
      response and extracellular matrix remodeling are essential for recovery. MMP-2
      could play a key role in epithelial repair after VILI and acute respiratory
      distress syndrome.

PMID- 21743032
TI  - Control: patients' aggression in psychiatric settings.
AB  - Psychiatric patient assaults on staff are a serious problem, affecting staff,
      patients, and organizations. To understand the etiology of aggressive events,
      researchers have documented characteristics of aggressive patients, their
      victims, and to a lesser degree, the patient-provider interaction. Missing in the
      literature is how staff's different perceptions of aggressive incidents might
      impact their reactions. In this study, we conducted in-depth, semistructured
      interviews with 11 health care professionals working in a psychiatric ward in one
      Israeli psychiatric hospital. Through content analysis, we revealed two main
      themes: patients' and providers' controllability over patients' aggression. From
      the intersection of these two themes, four prototypes of the aggressive encounter
      emerged: the power struggle, the therapeutic encounter, inverse power relations,
      and victim-to-victim encounters, each distinctively characterized by different
      emotional, cognitive, and behavioral responses. We discuss our findings in light
      of attribution theory, which carries important theoretical and practical
      implications for handling aggression.

PMID- 21743033
TI  - Effect of mechanical loading on electrical conductivity in porcine TMJ discs.
AB  - The objective of this study was to examine the impact of mechanical loading on
      solute transport in porcine temporomandibular joint (TMJ) discs using the
      electrical conductivity method. The electrical conductivity, as well as ion
      diffusivity, of TMJ discs was determined under confined compression with 3
      strains in 5 disc regions. The average electrical conductivity over the 5 regions
      (mean +/- SD) at 0% strain was 3.10 +/- 0.68 mS/cm, decreased to 2.76 +/- 0.58
      mS/cm (-11.0%) at 10% strain, and 2.38 +/- 0.55 mS/cm (-22.2%) at 20% compressive
      strain. Correspondingly, the average relative ion diffusivity (mean +/- SD) at 0%
      strain was 0.273 +/- 0.055, decreased to 0.253 +/- 0.048 (-7.3%) at 10% strain,
      and 0.231 +/- 0.048 (-15.4%) at 20% compressive strain. These results indicated
      that compressive strain impeded solute transport in the TMJ disc. Furthermore,
      our results showed that the transport properties of TMJ discs were region
      dependent. The electrical conductivity and ion diffusivity in the anterior region
      were significantly higher than in the posterior region. This regional difference
      is likely due to the significant differences of tissue hydration between these 2
      regions. This study provides important insight into the electrical and solute
      transport behaviors in TMJ discs under mechanical loading and aids in the
      understanding of TMJ pathophysiology related to tissue nutrition.

PMID- 21743034
TI  - Gene regulation in S. mutans: complex control in a complex environment.
AB  - Dental caries is a chronic infectious disease of multifactorial etiology that
      derives from the interplay among cariogenic bacteria on the dentition, the host
      diet, and other environmental exposures. Streptococcus mutans proliferates as a
      biofilm on the tooth surface, where it obtains nutrients and metabolizes
      fermentable dietary carbohydrates. The accumulation of lactic acid as a by
      product of fermentation results in acidification of the plaque biofilm and
      demineralization of tooth enamel, marking the onset of decay. The ability of S.
      mutans to respond to environmental stresses presented by salivary flow, acid pH,
      oxidative stress, and changes in carbohydrate source and availability is
      essential for its survival and predominance in caries lesions. Importantly, S.
      mutans has evolved a network of regulators to integrate its cellular response to
      environmental change. Herein we describe the latest insights into global gene
      regulation in S. mutans, including mechanisms of signal transduction, carbon
      catabolite repression, and quorum-sensing. An improved understanding of these
      regulatory networks can provide a basis for novel therapeutic applications aimed
      at treating and/or preventing caries.

PMID- 21743035
TI  - Expression of the human apoE2 isoform in adipocytes: altered cellular processing
      and impaired adipocyte lipogenesis.
AB  - Expression of apoE in adipocytes has been shown to have an important role in
      modulating adipocyte triglyceride (TG) metabolism and gene expression that is
      independent of circulating and extracellular apoE. The impact of adipocyte
      expression of common human apoE isoforms was evaluated using adipocytes harvested
      from human apoE2, -3, and -4 knock-in mice. Expression of the apoE2 isoform was
      associated with an increase in adipocyte apoE gene expression and apoE synthesis.
      Newly synthesized apoE2 was unstable in adipocytes and demonstrated increased
      degradation and decreased secretion. ApoE2-expressing mice were hyperlipidemic,
      and had increased size of gonadal fat pads and of adipocytes, compared with apoE3
      mice. In isolated cells, however, expression of the apoE2 isoform produced
      defective lipogenesis and increased TG hydrolysis. Incubation of adipose tissue
      with apoE3-containing TG-rich lipoproteins resulted in a significant increase in
      TG in adipose tissue from apoE3 and -E4 mice, but not apoE2 mice. Reduced
      capacity to internalize FFA as lipogenic substrate contributed to defective
      lipogenesis. Newly synthesized apoE2 is unstable in adipocytes and results in
      decreased adipocyte TG synthesis and defective FA uptake. These changes
      recapitulate those observed in apoE knockout adipocytes and have implications for
      understanding metabolic disturbances in humans expressing the E2 isoform.

PMID- 21743036
TI  - SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL.
AB  - Recent studies have established SIRT1 as an important regulator of lipid
      metabolism, although the mechanism of its action at the molecular level has not
      been revealed. Here, we show that knockdown of SIRT1 with the help of small
      hairpin RNA decreases basal and isoproterenol-stimulated lipolysis in cultured
      adipocytes. This effect is attributed, at least in part, to the suppression of
      the rate-limiting lipolytic enzyme, adipose triglyceride lipase (ATGL), at the
      level of transcription. Mechanistically, SIRT1 controls acetylation status and
      functional activity of FoxO1 that directly binds to the ATGL promoter and
      regulates ATGL gene transcription. We have also found that depletion of SIRT1
      decreases AMP-dependent protein kinase (AMPK) activity in adipocytes. To
      determine the input of AMPK in regulation of lipolysis, we have established a
      stable adipose cell line that expresses a dominant-negative alpha1 catalytic
      subunit of AMPK under the control of the inducible TET-OFF lentiviral expression
      vector. Reduction of AMPK activity does not have a significant effect on the
      rates of lipolysis in this cell model. We conclude, therefore, that SIRT1
      controls ATGL transcription primarily by deacetylating FoxO1.

PMID- 21743037
TI  - Memory self-efficacy predicts responsiveness to inductive reasoning training in
      older adults.
AB  - OBJECTIVES: In the current study, we assessed the relationship between memory
      self-efficacy at pretest and responsiveness to inductive reasoning training in a
      sample of older adults. METHODS: Participants completed a measure of self
      efficacy assessing beliefs about memory capacity. Participants were then randomly
      assigned to a waitlist control group or an inductive reasoning training
      intervention. Latent change score models were used to examine the moderators of
      change in inductive reasoning. RESULTS: Inductive reasoning showed clear
      improvements in the training group compared with the control. Within the training
      group, initial memory capacity beliefs significantly predicted change in
      inductive reasoning such that those with higher levels of capacity beliefs showed
      greater responsiveness to the intervention. Further analyses revealed that self
      efficacy had effects on how trainees allocated time to the training materials
      over the course of the intervention. DISCUSSION: Results indicate that self
      referential beliefs about cognitive potential may be an important factor
      contributing to plasticity in adulthood.

PMID- 21743038
TI  - Social cognitive influences on physical activity behavior in middle-aged and
      older adults.
AB  - OBJECTIVES: The purpose of the current study was to prospectively test the
      utility of a social cognitive theory (SCT) model of physical activity behavior
      over an 18-month period in middle-aged and older adults (N = 321; M age = 63.8
      years). METHODS: Participants completed measures of self-efficacy, disability
      limitations, goals, outcome expectations, and physical activity at baseline and
      follow-up. Self-efficacy was hypothesized to influence physical activity both
      directly and indirectly through goals and outcome expectations. Relationships
      were examined using panel analysis within a covariance modeling framework.
      RESULTS: The model provided an excellent fit to the data (chi(2) = 36.16, df =
      30, p = .20; comparative fit index = 1.00; root mean square error of
      approximation = .03). At baseline, self-efficacy was directly related to outcome
      expectations, disability limitations, goals, and physical activity and indirectly
      related to physical activity through physical outcome expectations. Changes in
      self-efficacy were significantly related to residual changes in outcome
      expectations, disability limitations, goals, and physical activity and indirectly
      related to residual changes in physical activity through changes in physical and
      social outcome expectations. DISCUSSION: These results provide further support
      for the use of SCT to physical activity behavior in middle-aged and older adults.
      Self-efficacy influenced physical activity both directly and indirectly via
      outcome expectations, suggesting that these variables should be targeted in
      physical activity interventions for middle-aged and older adults.

PMID- 21743039
TI  - Losing one's grip: a bivariate growth curve model of grip strength and nonverbal
      reasoning from age 79 to 87 years in the Lothian Birth Cohort 1921.
AB  - OBJECTIVES: Grip strength and reasoning are associated in old age. This is one of
      the few longitudinal studies addressing whether aging of one causes decline in
      the other or whether they share causal influences. METHODS: The Lothian Birth
      Cohort 1921 were assessed for grip strength and nonverbal reasoning at ages M =
      79 (N = 550), M = 83 (N = 321), and M = 87 (N = 207). Associations among
      intercepts and slopes for grip strength and reasoning and covariates were
      examined by fitting a bivariate growth curve structural equation model. RESULTS:
      Grip strength and reasoning declined with age. They were each significantly
      correlated on each occasion. Their intercepts were significantly correlated (.20)
      but not their slopes. Neither intercept was significantly associated with its own
      or the other's slope. Better reasoning was associated with higher childhood
      intelligence, more professional occupations, male sex, and being taller. There
      were no significant reasoning slope associations. Stronger grip strength was
      associated with male sex, being taller, and drinking less alcohol. Women showed
      less age-related decline in grip strength. DISCUSSION: Physical and mental
      "grips" declined in the ninth decade of life. Their levels were significantly
      correlated; their slopes were not. There was no evidence for reciprocal dynamic
      influences nor for shared associations.

PMID- 21743040
TI  - Social exchanges and subjective well-being: do sources of positive and negative
      exchanges matter?
AB  - OBJECTIVES: To decompose the effects of positive and negative social exchanges on
      well-being in terms of relationship type (vertically extended family,
      horizontally extended family, or nonfamily) and subjective closeness (close vs.
      peripheral). METHODS: One thousand and five Chinese older adults rated each
      network member on positive and negative exchanges, which were aggregated for each
      relationship type and closeness category. Regression analyses estimated the
      influences of positive and negative exchanges on well-being, controlling for
      network size, health, and demographic factors. RESULTS: Social exchanges with
      close and peripheral vertical family members as well as close horizontal family
      members were associated with well-being, whereas exchanges with nonkin did not
      contribute independent effects. These results were similar for both positive and
      negative exchanges. DISCUSSION: Well-being is determined not just by social
      exchanges but also by where they come from. In this regard, the vertical family,
      the horizontal family, and the nonfamily represent a hierarchy of preference for
      Chinese older adults, which, to some extent, reflects the influence of familism.

PMID- 21743041
TI  - Do positive psychological characteristics modify the associations of physical
      performance with functional decline and institutionalization? Findings from the
      longitudinal aging study Amsterdam.
AB  - OBJECTIVES: To investigate whether 3 positive psychological characteristics,
      related to sense of control, modify the associations of physical performance
      levels with subsequent functional decline and institutionalization. METHOD: One
      thousand five hundred and thirty-two men and women participating in the
      Longitudinal Aging Study Amsterdam and not living in an institution in 2005-2006
      were included. Mastery, self-efficacy, investment in independence, and objective
      physical performance scores were ascertained in 2005-2006. Functional decline and
      institutionalization were assessed after 3 years of follow-up. RESULTS: The
      association between lower physical performance levels and increased odds of
      functional decline was modified by investment in independence, with a weaker
      association found among people with higher investment in independence scores than
      in people with lower scores even after adjustment for covariates. The association
      between lower physical performance levels and higher odds of institutionalization
      was marginally weaker among those people with above median levels of mastery
      (test of interaction p = .08). In men, an association between general self
      efficacy and functional decline was found and maintained after adjustments.
      CONCLUSIONS: Positive psychological characteristics, related to sense of control,
      play a role in the transition between stages in the disablement process. Specific
      psychological characteristics may be associated with different stages of the
      disablement process and may in turn be affected by disablement.

PMID- 21743042
TI  - Volunteer transitions among older adults: the role of human, social, and cultural
      capital in later life.
AB  - OBJECTIVES: We aim to understand how human, social, and cultural capitals are
      associated with the volunteer process, that is, engagement (starting), intensity
      (number of hours), and cessation (stopping), among older adults. METHOD: Data
      from the 2000 through 2008 Health and Retirement Study and the 2001 through 2009
      Consumption and Activity Mail Survey provide a sample of 4,526 respondents.
      Random-effects pooled time series analyses incorporate not only the presence of
      various types of capital but also the quality of that capital. RESULTS: Human and
      cultural capitals were positively associated with increased volunteer
      involvement. Effects of social capital (relationships in the family, employment
      status, and the community) depended on the quality of the relationships, not
      necessarily on their presence alone. DISCUSSION: Results suggest that bolstering
      older adults' capitals, particularly among lower socioeconomic status groups, can
      increase volunteer engagement and intensity and reduce cessation. Additionally, a
      variety of organizational policies including respite programs for caregivers and
      employer policies allowing employees to reduce their work hours might indirectly
      affect participation rates and commitment. Potential pools of volunteers exist in
      families, workplaces, and religious organizations, but more research is necessary
      to identify how to recruit and retain individuals in social networks where
      volunteer participatory rates are low.

PMID- 21743044
TI  - Life-span socioeconomic trajectory, nativity, and cognitive aging in Mexican
      Americans: the Sacramento Area Latino Study on Aging.
AB  - OBJECTIVES: Early life circumstances influence health across the life span.
      Migration and ethnicity may modify the lifetime trajectory of socioeconomic
      status (SES) and lead to heterogeneity in cognitive aging in later life. METHODS:
      We examined the effects of both lifetime socioeconomic trajectory and cumulative
      disadvantage from childhood through adulthood on late life cognitive performance
      in a 9-year cohort of 1,789 Mexican Americans aged 60-100 years in 1998-1999.
      RESULTS: Compared with those with low SES sustained over the life course, we
      found that those with more advantaged lifetime SES trajectories experienced fewer
      declines on a test of global cognitive function and a short-term verbal memory
      test. These associations are larger in first- and second-generation immigrant
      families. DISCUSSION: Heterogeneity of cognitive aging among diverse race/ethnic
      groups may be influenced by intergenerational changes in SES, cultural norms, and
      behaviors and changes in health related to changes in the social and physical
      environment.

PMID- 21743045
TI  - Intraindividual coupling of daily stressors and cognitive interference in old
      age.
AB  - OBJECTIVES: The current study examined emotional and cognitive reactions to daily
      stress. We examined the psychometric properties of a short cognitive interference
      measure and how cognitive interference was associated with measures of daily
      stress and negative affect (NA) between persons and within persons over time.
      METHODS: A sample of 87 older adults (M(age) = 83, range = 70-97, 28% male)
      completed measures of daily stress, cognitive interference, and NA on 6 days
      within a 14-day period. RESULTS: The measure yielded a single-factor solution
      with good reliability both between and within persons. At the between-person
      level, NA accounted for the effects of daily stress on individual differences in
      cognitive interference. At the within-person level, NA and daily stress were
      unique predictors of cognitive interference. Furthermore, the within-person
      effect of daily stress on cognitive interference decreased significantly with
      age. DISCUSSION: These results support theoretical work regarding associations
      among stress, NA, and cognitive interference, both across persons and within
      persons over time.

PMID- 21743046
TI  - Cognitive functioning in midlife and old age: combined effects of psychosocial
      and behavioral factors.
AB  - OBJECTIVES: This study examined the joint protective contribution of psychosocial
      and behavioral factors to cognitive functioning and 10-year change, beyond the
      influence of sociodemographic factors, physical risk factors, health status, and
      engagement in cognitive activities. METHODS: Participants were from the National
      Study of Midlife in the United States (MIDUS), ages 32-84 at Time 2, and a
      subsample, the Boston Longitudinal Study (BOLOS), ages 34-84 at Time 2. We
      computed a composite protective measure including control beliefs, quality of
      social support, and physical exercise variables at two occasions, 9-10 years
      apart. Cognition was assessed at Time 2 in MIDUS and at both occasions in BOLOS.
      Multiple regressions were used for analysis. RESULTS: In MIDUS, the more of the
      protective factors, the better the cognitive performance, and the protective
      composite moderated education differences in memory. In BOLOS, the Time 1
      composite predicted change in reasoning abilities, with a greater protective
      effect for those with lower education. DISCUSSION: A combination of modifiable
      psychosocial and behavioral factors has both concurrent and long-term protective
      effects on cognition in adulthood. The results are promising in that educational
      disparities in memory and reasoning were reduced, suggesting possible
      interventions to protect against cognitive declines.

PMID- 21743047
TI  - Assessment of cognition using surveys and neuropsychological assessment: the
      Health and Retirement Study and the Aging, Demographics, and Memory Study.
AB  - OBJECTIVES: This study examines the similarity of cognitive assessments using 1
      interview in a large population study, the Health and Retirement Study (HRS), and
      a subsample in which a detailed neuropsychiatric assessment has been performed
      (Aging, Demographics, and Memory Study [ADAMS]). METHODS: Respondents are
      diagnosed in ADAMS as demented, cognitively impaired without dementia (CIND), or
      as having normal cognitive function. Multinomial logistic analysis is used to
      predict diagnosis using a variety of cognitive and noncognitive measures from the
      HRS and additional measures and information from ADAMS. RESULTS: The cognitive
      tests in HRS predict the ADAMS diagnosis in 74% of the sample able to complete
      the HRS survey on their own. Proxy respondents answer for a large proportion of
      HRS respondents who are diagnosed as demented in ADAMS. Classification of proxy
      respondents with some cognitive impairment can be predicted in 86% of the sample.
      Adding a small number of additional tests from ADAMS can increase each of these
      percentages to 84% and 93%, respectively. DISCUSSION: Cognitive assessment
      appropriate for diagnosis of dementia and CIND in large population surveys could
      be improved with more targeted information from informants and additional
      cognitive tests targeting other areas of brain function.

PMID- 21743048
TI  - Integrating health into cognitive aging: toward a preventive cognitive
      neuroscience of aging.
AB  - OBJECTIVES: We argue that age is a descriptive, and not explanatory, variable and
      consequently cannot account for the cognitive changes that often occur with
      aging. Once age is removed from consideration, other truly causal explanations
      for "cognitive aging" must be identified. We argue that health and disease
      represent an important class of explanatory variables for age-related cognitive
      changes. METHODS/RESULTS: We make this argument first by reviewing the prevalence
      of risk factors, disability, and subclinical and frank disease in the elderly
      population. We emphasize that the complexity of health effects rivals that of age
      on cognition while noting that most studies of cognitive aging rarely consider
      this complexity fully. We then consider in more detail the "vascular hypothesis,"
      which proposes that vascular diseases (e.g., stroke, heart disease) and their
      risk factors (e.g., hypertension) can explain aspects of cognitive decline in
      aging through their impact on circulatory and brain functions. Clinical
      implications of this hypothesis suggest that treatment of vascular risk factors
      might well reduce the incidence or severity of dementia syndromes. DISCUSSION: We
      conclude with a brief summary of approaches to further integrate aspects of
      health and disease into the study of "cognitive aging."

PMID- 21743049
TI  - Generating large-scale longitudinal data resources for aging research.
AB  - OBJECTIVES: The need for large studies and the types of large-scale data
      resources (LSDRs) are discussed along with their general scientific utility, role
      in aging research, and affordability. The diversification of approaches to large
      scale data resourcing is described in order to facilitate their use in aging
      research. METHODS: The need for LSDRs is discussed in terms of (a) large sample
      size; (b) longitudinal design; (c) as platforms for additional investigator
      initiated research projects; and (d) broad-based access to core genetic,
      biological, and phenotypic data. DISCUSSION: It is concluded that a "lite-touch,
      lo-tech, lo-cost" approach to LSDRs is a viable strategy for the development of
      LSDRs and would enhance the likelihood of LSDRs being established which are
      dedicated to the wide range of important aging-related issues.

PMID- 21743050
TI  - Intelligent Systems For Assessing Aging Changes: home-based, unobtrusive, and
      continuous assessment of aging.
AB  - OBJECTIVES: To describe a longitudinal community cohort study, Intelligent
      Systems for Assessing Aging Changes, that has deployed an unobtrusive home-based
      assessment platform in many seniors homes in the existing community. METHODS:
      Several types of sensors have been installed in the homes of 265 elderly persons
      for an average of 33 months. Metrics assessed by the sensors include total daily
      activity, time out of home, and walking speed. Participants were given a computer
      as well as training, and computer usage was monitored. Participants are assessed
      annually with health and function questionnaires, physical examinations, and
      neuropsychological testing. RESULTS: Mean age was 83.3 years, mean years of
      education was 15.5, and 73% of cohort were women. During a 4-week snapshot,
      participants left their home twice a day on average for a total of 208 min per
      day. Mean in-home walking speed was 61.0 cm/s. Participants spent 43% of days on
      the computer averaging 76 min per day. DISCUSSION: These results demonstrate for
      the first time the feasibility of engaging seniors in a large-scale deployment of
      in-home activity assessment technology and the successful collection of these
      activity metrics. We plan to use this platform to determine if continuous
      unobtrusive monitoring may detect incident cognitive decline.

PMID- 21743051
TI  - An evaluation of analytical approaches for understanding change in cognition in
      the context of aging and health.
AB  - OBJECTIVES: In this article, we discuss the importance of studying the
      relationship between health and cognitive function, and some of the methods with
      which this relationship has been studied. METHODS: We consider the challenges
      involved, in particular operationalization of the health construct and causal
      inference in the context of observational data. We contrast the approaches taken,
      and review the questions addressed: whether health and cognition are associated,
      whether changes in health are associated with changes in cognition, and the
      degree of interdependency among their respective trajectories. RESULTS: A variety
      of approaches for understanding the association between cognition and health in
      aging individuals have been used. Much of the literature on cognitive change and
      health has relied on methods that are based at least in part on the
      reorganization of between-person differences (e.g., cross-lag analysis) rather
      than relying more fully on analysis of within-person change and joint analysis of
      individual differences in within-person change in cognition and health.
      DISCUSSION: We make the case for focusing on the interdependency between within
      person changes in health and cognition and suggest methods that would support
      this.

PMID- 21743052
TI  - Cognitive decline and the default American lifestyle.
AB  - OBJECTIVES: Upward trends in IQ, education, and mental work suggest that
      cognitive function among seniors should be rising strongly across cohorts. There
      is little sign of such improvement in recent decades, and some analyses find
      poorer function in the newer cohorts. This essay explores possible explanations
      of the anomaly. METHODS: Major long-term trends that might increase cognitive
      impairment are reviewed, and their implications are considered. RESULTS: Physical
      activity is declining, food is increasingly manufactured, body fat is increasing,
      diabetes and metabolic syndrome are on the rise, the number of prescription drugs
      per person is increasing, and the proportion of the population either old or
      obese is growing. DISCUSSION: Technological and economic development may lower
      the cognitive function needed for survival. They also lower physical activity in
      daily life. Sedentary work, transportation, and leisure undermine the aerobic and
      metabolic fitness required for the brain to perform well. Some prescription drugs
      impair cognitive function, and others do so when taken for many years or in
      combination with others. The growing fraction of the population that is either
      old or obese may further lower physical activity norms and requirements and
      substitute medical intervention for health, accelerating a trend toward cognitive
      impairment.

PMID- 21743053
TI  - Linking biological and cognitive aging: toward improving characterizations of
      developmental time.
AB  - OBJECTIVES: Chronological age is the most frequently employed predictor in life
      span developmental research, despite repeated assertions that it is best
      conceived as a proxy for true mechanistic changes that influence cognition across
      time. The present investigation explores the potential that selected functional
      biomarkers may contribute to the more effective conceptual and operational
      definitions of developmental time. METHODS: We used data from the Victoria
      Longitudinal Study to explore both static and dynamic biological or physiological
      markers that arguably influence process-specific mechanisms underlying cognitive
      changes in late life. Multilevel models were fit to test the dynamic coupling
      between change in theoretically relevant biomarkers (e.g., grip strength,
      pulmonary function) and change in select cognitive measures (e.g., executive
      function, episodic and semantic memory). RESULTS: Results showed that,
      independent of the passage of developmental time (indexed as years in study),
      significant time-varying covariation was observed linking corresponding declines
      for select cognitive outcomes and biological markers. DISCUSSION: Our findings
      support the interpretation that cognitive decline is not due to chronological
      aging per se but rather reflects multiple causal factors from a broad range of
      biological and physical health domains that operate along the age continuum.

PMID- 21743054
TI  - Associations between cognitive function and naturally occurring daily cortisol
      during middle adulthood: timing is everything.
AB  - OBJECTIVES: We examined associations between cognitive function (CF) and the
      naturally occurring daily cortisol levels using data from the Midlife in the
      United States survey and the National Study of Daily Experiences. METHODS: A
      national sample of 1,500 (mean age = 57 years; range = 33-84, 56% female)
      completed a phone-based battery of cognitive tasks and 3-6 months later provided
      saliva samples upon waking, 30 min after waking, at lunch time, and at bedtime on
      4 consecutive days. RESULTS: Higher CF, particularly executive function, was
      associated with healthier daily cortisol profiles, including a steeper diurnal
      cortisol slope, higher morning cortisol levels, and lower afternoon and evening
      cortisol levels. DISCUSSION: The results indicate that better CF is associated
      with healthier profiles of naturally occurring cortisol and underscore the
      importance of the timing of cortisol sampling.

PMID- 21743055
TI  - Health and cognition in aging research.

PMID- 21743056
TI  - Adolescent IQ and survival in the Wisconsin longitudinal study.
AB  - OBJECTIVE: This study attempts to explain the ubiquitous positive correlation
      between cognitive ability (IQ) and survival. METHODS: A sample of 10,317
      Wisconsin high school graduates of 1957 was followed until 2009, from ages 18 to
      68 years. Mortality was analyzed using a Weibull survival model that includes
      gender, social background, Henmon-Nelson IQ, and rank in high school class.
      RESULTS: Rank in high school class, a cumulative measure of responsible
      performance during high school, entirely mediates the relationship between
      adolescent IQ and survival. Its effect on survival is 3 times greater than that
      of IQ, and it accounts for about 10% of the female advantage in survival.
      DISCUSSION: Cognitive functioning may improve survival by promoting responsible
      and timely patterns of behavior that are firmly in place by late adolescence.
      Prior research suggests that conscientiousness, one of the "Big Five" personality
      characteristics, plays a key role in this relationship.

PMID- 21743058
TI  - The fate of hydraulically redistributed water in a semi-arid zone eucalyptus
      species.
AB  - Although hydraulic redistribution has been observed for a range of tree species,
      including Eucalyptus kochii subsp. borealis (C. Gardner) D. Nicolle, there is
      limited direct evidence that water taken up by deep roots in moist soil is in
      fact exuded by shallow roots in dry soil. This paper reports an experiment
      designed to test this hypothesis. Water enriched with deuterium was added to the
      groundwater via a slotted tube at 4.5 m depth below 5-year-old E. kochii subsp.
      borealis trees. Nocturnal sap flow increased markedly immediately after deep
      irrigation, indicating that the trees were using water from this depth. Two weeks
      later, samples of surface soil and xylem water were found to contain levels of
      deuterium up to 30% higher than soils and xylem water from a control plot upslope
      of the main treatment plot. This is strong evidence that trees used groundwater
      and that efflux of important amounts of hydraulically redistributed water
      occurred via the roots of E. kochii subsp. borealis.

PMID- 21743057
TI  - Genome-wide association study identifies new prostate cancer susceptibility loci.
AB  - Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males
      in developed countries and the second leading cause of cancer mortality, yet
      little is known regarding its etiology and factors that influence clinical
      outcome. Genome-wide association studies (GWAS) of PrCa have identified at least
      30 distinct loci associated with small differences in risk. We conducted a GWAS
      in 2782 advanced PrCa cases (Gleason grade >= 8 or tumor stage C/D) and 4458
      controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico
      replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa
      cases and 6732 controls, we identified a new susceptibility locus associated with
      overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 * 10(-8)). We also confirmed a
      locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 * 10(-9)). The
      estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for
      rs902774) did not differ between advanced and non-advanced PrCa (case-only test
      for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be
      needed to assess whether these or other loci are differentially associated with
      PrCa subtypes.

PMID- 21743059
TI  - A model of heat transfer in sapwood and implications for sap flux density
      measurements using thermal dissipation probes.
AB  - A variety of thermal approaches are used to estimate sap flux density in stems of
      woody plants. Models have proved valuable tools for interpreting the behavior of
      heat pulse, heat balance and heat field deformation techniques, but have seldom
      been used to describe heat transfer dynamics for the heat dissipation method.
      Therefore, to better understand the behavior of heat dissipation probes, a model
      was developed that takes into account the thermal properties of wood, the
      physical dimensions and thermal characteristics of the probes, and the conductive
      and convective heat transfer that occurs due to water flow in the sapwood. Probes
      were simulated as aluminum tubes 20 mm in length and 2 mm in diameter, whereas
      sapwood, heartwood and bark each had a density and water fraction that determined
      their thermal properties. Base simulations assumed a constant sap flux density
      with sapwood depth and no wounding or physical disruption of xylem beyond the 2
      mm diameter hole drilled for probe installation. Simulations across a range of
      sap flux densities showed that the dimensionless quantity k [defined as
      (DeltaT(m) -DeltaT)/DeltaT, where DeltaT(m) is the temperature differential
      (DeltaT) between the heated and unheated probe under zero-flow conditions] was
      dependent on the thermal conductivity of the sapwood. The relationship between
      sap flux density and k was also sensitive to radial gradients in sap flux density
      and to xylem disruption near the probe. Monte Carlo analysis in which 1000
      simulations were conducted while simultaneously varying thermal conductivity and
      wound diameter revealed that sap flux density and k showed considerable departure
      from the original calibration equation used with this technique. The departure
      was greatest for variation in sap flux density typical of ring-porous species.
      Depending on the specific combination of thermal conductivity and wound diameter,
      use of the original calibration equation resulted in an 81% under- to 48%
      overestimation of sap flux density at modest flux rates. Future studies should
      verify these simulations and assess their utility in estimating sap flux density
      for this widely used technique.

PMID- 21743060
TI  - Annotation concept synthesis and enrichment analysis: a logic-based approach to
      the interpretation of high-throughput experiments.
AB  - MOTIVATION: Annotation Enrichment Analysis (AEA) is a widely used analytical
      approach to process data generated by high-throughput genomic and proteomic
      experiments such as gene expression microarrays. The analysis uncovers and
      summarizes discriminating background information (e.g. GO annotations) for sets
      of genes identified by experiments (e.g. a set of differentially expressed genes,
      a cluster). The discovered information is utilized by human experts to find
      biological interpretations of the experiments. However, AEA isolates and tests
      for overrepresentation only individual annotation terms or groups of similar
      terms and is limited in its ability to uncover complex phenomena involving
      relationship between multiple annotation terms from various knowledge bases.
      Also, AEA assumes that annotations describe the whole object of interest, which
      makes it difficult to apply it to sets of compound objects (e.g. sets of protein
      protein interactions) and to sets of objects having an internal structure (e.g.
      protein complexes). RESULTS: We propose a novel logic-based Annotation Concept
      Synthesis and Enrichment Analysis (ACSEA) approach. ACSEA fuses inductive logic
      reasoning with statistical inference to uncover more complex phenomena captured
      by the experiments. We evaluate our approach on large-scale datasets from several
      microarray experiments and on a clustered genome-wide genetic interaction network
      using different biological knowledge bases. The discovered interpretations have
      lower P-values than the interpretations found by AEA, are highly integrative in
      nature, and include analysis of quantitative and structured information present
      in the knowledge bases. The results suggest that ACSEA can boost effectiveness of
      the processing of high-throughput experiments. CONTACT: mjiline@site.uottawa.ca.

PMID- 21743061
TI  - A Lasso regression model for the construction of microRNA-target regulatory
      networks.
AB  - MOTIVATION: MicroRNAs have recently emerged as a major class of regulatory
      molecules involved in a broad range of biological processes and complex diseases.
      Construction of miRNA-target regulatory networks can provide useful information
      for the study and diagnosis of complex diseases. Many sequence-based and
      evolutionary information-based methods have been developed to identify miRNA-mRNA
      targeting relationships. However, as the amount of available miRNA and gene
      expression data grows, a more statistical and systematic method combining
      sequence-based binding predictions and expression-based correlation data becomes
      necessary for the accurate identification of miRNA-mRNA pairs. RESULTS: We
      propose a Lasso regression model for the identification of miRNA-mRNA targeting
      relationships that combines sequence-based prediction information, miRNA co
      regulation, RISC availability and miRNA/mRNA abundance data. By comparing this
      modelling approach with two other known methods applied to three different
      datasets, we found that the Lasso regression model has considerable advantages in
      both sensitivity and specificity. The regression coefficients in the model can be
      used to determine the true regulatory efficacies in tissues and was demonstrated
      using the miRNA target site type data. Finally, by constructing the miRNA
      regulatory networks in two stages of prostate cancer (PCa), we found the several
      significant miRNA-hubbed network modules associated with PCa metastasis. In
      conclusion, the Lasso regression model is a robust and informative tool for
      constructing the miRNA regulatory networks for diagnosis and treatment of complex
      diseases. AVAILABILITY: The R program for predicting miRNA-mRNA targeting
      relationships using the Lasso regression model is freely available, along with
      the described datasets and resulting regulatory network, at
      http://biocompute.bmi.ac.cn/CZlab/alarmnet/. The source code is open for
      modification and application to other miRNA/mRNA expression datasets. CONTACT:
      zhangcg@bmi.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 21743062
TI  - CSO validator: improving manual curation workflow for biological pathways.
AB  - SUMMARY: Manual curation and validation of large-scale biological pathways are
      required to obtain high-quality pathway databases. In a typical curation process,
      model validation and model update based on appropriate feedback are repeated and
      requires considerable cooperation of scientists. We have developed a CSO (Cell
      System Ontology) validator to reduce the repetition and time during the curation
      process. This tool assists in quickly obtaining agreement among curators and
      domain experts and in providing a consistent and accurate pathway database.
      AVAILABILITY: The tool is available on http://csovalidator.csml.org. CONTACT:
      masao@hgc.jp.

PMID- 21743063
TI  - Intracranial dissection mimicking transient cerebral arteriopathy in childhood
      arterial ischemic stroke.
AB  - Transient cerebral arteriopathy is a frequent cause of childhood arterial
      ischemic stroke. Differentiating this condition from intracranial carotid artery
      dissection is challenging but important for initial treatment. We describe 4
      cases from the International Pediatric Stroke Study of intracranial carotid
      artery dissection, initially misdiagnosed as transient cerebral arteriopathy.
      Presentations were abrupt, with focal neurological deficits in 4, preceding
      headache in 3, and minor trauma in 1. Infarcts involved the anterior circulation,
      and magnetic resonance angiography showed unilateral arterial stenosis/occlusion.
      None had evidence of dissection. All received anticoagulation or thrombolysis.
      Three died from refractory intracranial hypertension. Intracranial carotid artery
      dissection was confirmed postmortem (n = 3) and on dedicated MR wall imaging
      showing intramural hematoma (n = 1). In differentiating transient cerebral
      arteriopathy from intracranial carotid artery dissection, routine magnetic
      resonance angiography is unreliable and adjunctive conventional angiography,
      gadolinium magnetic resonance angiography, or dedicated MRI wall imaging should
      be considered.

PMID- 21743064
TI  - The microtubule stabilizer patupilone (epothilone B) is a potent radiosensitizer
      in medulloblastoma cells.
AB  - Concurrent radiochemotherapy for medulloblastoma includes the microtubule
      disrupting agent vincristine; however, vincristine alone or as part of a combined
      treatment regimen is highly toxic. A major goal is therefore to replace
      vincristine with novel potent chemotherapeutic agents-in particular, with
      microtubule stabilizing and destabilizing compounds-with a larger therapeutic
      window. Here, we investigated the antiproliferative, cytotoxic and
      radiosensitizing effect of patupilone (epothilone B [EPO906]), a novel, non
      taxane-related and nonneurotoxic microtubule-stabilizing agent in human
      medulloblastoma cell lines. The antiproliferative and cytotoxic effects of
      patupilone alone and in combination with ionizing radiation was determined in the
      3 representative human medulloblastoma cell lines D341Med, D425Med, and DAOY.
      Patupilone alone effectively reduced the proliferative activity and clonogenicity
      of all medulloblastoma cell lines tested at picomolar concentrations (50-200 pM)
      and resulted in an at least additive anticlonogenic effect in combination with
      clinically relevant doses of ionizing radiation (2 or 5 Gy). Cell-cycle analysis
      revealed a sequential G2-M arrest and sub-G1 accumulation in a dose- and
      treatment-dependent manner after exposure to patupilone. In tumor xenografts
      derived from D425Med cells, a minimal treatment regimen with patupilone and
      fractionated irradiation (1 * 2 mg/kg plus 3 * 3 Gy) resulted in an extended
      tumor growth delay for the 2 single treatment modalities alone and a supra
      additive treatment response for the combined treatment modality, with complete
      tumor regressions. These results demonstrate the potent efficacy of patupilone
      against medulloblastoma cell lines and indicate that patupilone represents a
      promising candidate to replace vincristine as part of a combined treatment
      strategy with ionizing radiation.

PMID- 21743065
TI  - Prevalence and prognostic significance of hyponatraemia in outpatients with
      chronic heart failure.
AB  - AIM: Hyponatraemia has been reported to be a potent predictor of poor outcome in
      patients hospitalized for heart failure (HF). The aim of the study was to
      determine the prevalence and prognostic significance of hyponatraemia in a large
      cohort of HF outpatients followed in clinics participating in the Danish Heart
      Failure Clinics Network. METHODS AND RESULTS: The study population consisted of
      consecutive patients referred for HF management in 18 Danish heart failure
      clinics. Overall, 2863 patients (83%) had a normal plasma sodium (p-sodium) level
      and 602 patients (17%) had hyponatraemia with a p-sodium level <136 mmol/L.
      Outcome data were obtained from a validated, national registry. Patients were
      elderly with a mean age of 68 years. The mean P-[Na+] was 139.6 +/- 2.4 mmol/L
      among patients with normonatraemia and 132.4 +/- 3.2 mmol/L among patients with
      hyponatraemia. In multivariate Cox Proportional Hazard Models adjusted for
      confounders (age, gender, hospitalization within the last 90 days, loop
      diuretics, creatinine level, systolic blood pressure, New York Heart Association
      class III-IV, left ventricular ejection fraction <0.46, ischaemic heart disease
      and diabetes) hyponatraemic patients had increased risk of hospitalization or
      death [hazard ratio (HR) 1.2 (95% confidence interval (CI) 1.0-1.4, P = 0.011)].
      Hyponatraemia was also an independent predictor of all-cause mortality [HR 1.5
      (95% CI 1.2-1.9, P< 0.001)]. There was no interaction between hyponatraemia and
      the covariables on outcome in the multivariable models. CONCLUSION: The presence
      of hyponatraemia in outpatients with HF is associated with increased risk of
      hospitalization or death.

PMID- 21743066
TI  - Computational oncology.
AB  - Oncology research has traditionally been conducted using techniques from the
      biological sciences. The new field of computational oncology has forged a new
      relationship between the physical sciences and oncology to further advance
      research. By applying physics and mathematics to oncologic problems, new insights
      will emerge into the pathogenesis and treatment of malignancies. One major area
      of investigation in computational oncology centers around the acquisition and
      analysis of data, using improved computing hardware and software. Large databases
      of cellular pathways are being analyzed to understand the interrelationship among
      complex biological processes. Computer-aided detection is being applied to the
      analysis of routine imaging data including mammography and chest imaging to
      improve the accuracy and detection rate for population screening. The second
      major area of investigation uses computers to construct sophisticated
      mathematical models of individual cancer cells as well as larger systems using
      partial differential equations. These models are further refined with clinically
      available information to more accurately reflect living systems. One of the major
      obstacles in the partnership between physical scientists and the oncology
      community is communications. Standard ways to convey information must be
      developed. Future progress in computational oncology will depend on close
      collaboration between clinicians and investigators to further the understanding
      of cancer using these new approaches.

PMID- 21743067
TI  - Combined spinal and epidural anaesthesia and maternal intrapartum temperature
      during vaginal delivery: a randomized clinical trial.
AB  - BACKGROUND: We determined the association between combined spinal-epidural (CSE)
      anaesthesia and an increase in maternal intrapartum temperature and intrapartum
      fever. METHODS: A randomized, open clinical trial was performed with 70 pregnant
      women, 35 receiving CSE and 35 receiving only non-pharmacological methods of pain
      relief during delivery. Association between CSE and changes in the patient's
      temperature, the risk of maternal fever, and other maternal and perinatal
      outcomes was determined at a 5% significance level. Number needed to harm (NNH)
      was calculated for maternal fever. RESULTS: Patients receiving CSE anaesthesia
      during vaginal delivery experienced a significant increase in intrapartum
      temperature and five (14%) developed fever, whereas no cases occurred in the
      group receiving only non-pharmacological methods of pain relief (P=0.027). None
      of the women who developed fever received antibiotics or were submitted to
      further investigation; however, all progressed without complication. No case of
      chorioamnionitis or any maternal or neonatal infection was detected. NNH for
      maternal fever was 7.0 (95% confidence interval: 3.8-51.9). CONCLUSIONS: The use
      of CSE is associated with a significant increase in maternal temperature and in
      the incidence of intrapartum maternal fever. However, the increase in maternal
      temperature does not appear to provoke any deleterious effects on the mother or
      child.

PMID- 21743068
TI  - Performance evaluation of paediatric propofol pharmacokinetic models in healthy
      young children.
AB  - BACKGROUND: The performance of eight currently available paediatric propofol
      pharmacokinetic models in target-controlled infusions (TCIs) was assessed, in
      healthy children from 3 to 26 months of age. METHODS: Forty-one, ASA I-II
      children, aged 3-26 months were studied. After the induction of general
      anaesthesia with sevoflurane and remifentanil, a propofol bolus dose of 2.5 mg
      kg(-1) followed by an infusion of 8 mg kg(-1) h(-1) was given. Arterial blood
      samples were collected at 1, 2, 3, 5, 10, 20, 40, and 60 min post-bolus, at the
      end of surgery, and at 1, 3, 5, 30, 60, and 120 min after stopping the infusion.
      Model performance was visually inspected with measured/predicted plots. Median
      performance error (MDPE) and the median absolute performance error (MDAPE) were
      calculated to measure bias and accuracy of each model. RESULTS: Performance of
      the eight models tested differed markedly during the different stages of propofol
      administration. Most models underestimated propofol concentration 1 min after the
      bolus dose, suggesting an overestimation of the initial volume of distribution.
      Six of the eight models tested were within the accepted limits of performance
      (MDPE<20% and MDAPE<30%). The model derived by Short and colleagues performed
      best. CONCLUSIONS: Our results suggest that six of the eight models tested
      perform well in young children. Since most models overestimate the initial volume
      of distribution, the use for TCI might result in the administration of larger
      bolus doses than necessary.

PMID- 21743069
TI  - Radiation doses to paediatric patients and comforters undergoing chest X rays.
AB  - Pneumonia is an important cause of hospital admission among children in the
      developed world and it is estimated to be responsible for 3-18 % of all
      paediatric admissions. Chest X ray is an important examination for pneumonia
      diagnosis and for evaluation of complications. This study aims to determine the
      entrance surface dose (ESD), organ, effective doses and propose a local
      diagnostic reference level. The study was carried out at the university hospital
      of Larissa, Greece. Patients were divided into three groups: organ and effective
      doses were estimated using National Radiological Protection Board software. The
      ESD was determined by thermoluminescent dosemeters for 132 children and 76
      comforters. The average ESD value was 55 +/- 8 uGy. The effective dose for
      patients was 11.2 +/- 5 uSv. The mean radiation dose for comforter is 22 +/- 3
      uGy. The radiation dose to the patients is well within dose constraint, in the
      light of the current practice.

PMID- 21743070
TI  - Comparison of different methods for shielding design in computed tomography.
AB  - The purpose of this work is to compare different methods for shielding
      calculation in computed tomography (CT). The BIR-IPEM (British Institute of
      Radiology and Institute of Physics in Engineering in Medicine) and NCRP (National
      Council on Radiation Protection) method were used for shielding thickness
      calculation. Scattered dose levels and calculated barrier thickness were also
      compared with those obtained by scatter dose measurements in the vicinity of a
      dedicated CT unit. Minimal requirement for protective barriers based on BIR-IPEM
      method ranged between 1.1 and 1.4 mm of lead demonstrating underestimation of up
      to 20 % and overestimation of up to 30 % when compared with thicknesses based on
      measured dose levels. For NCRP method, calculated thicknesses were 33 % higher
      (27-42 %). BIR-IPEM methodology-based results were comparable with values based
      on scattered dose measurements, while results obtained using NCRP methodology
      demonstrated an overestimation of the minimal required barrier thickness.

PMID- 21743071
TI  - Radiation dose and image quality for adult interventional cardiology in Chile: a
      national survey.
AB  - The aim of this work was to investigate the differences in dose settings and
      image quality among 10 X-ray systems used for interventional cardiology in Chile.
      Entrance surface air kerma (ESAK) was measured on a phantom of 20 cm thickness of
      polymethyl methacrylate slabs. Image quality was evaluated using DICOM images of
      a test object Leeds TOR 18-FG for cine mode acquisition, through the numerical
      parameters signal-to-noise ratio (SNR), high-contrast spatial resolution (HCSR)
      and figure of merit. ESAK rate values for fluoroscopy modes ranged between 7.1
      and 121.7 mGy min(-1). For cine mode, ESAK values per frame ranged from 63 to 400
      uGy fr(-1). SNR and HCSR parameters for cine mode varied from 4.8 to 8.6 and 0.4
      to 10, respectively. FOM values resulted from 6.9 to 64.5 among the different X
      ray systems. Results show important differences between systems and point out the
      need to launch an optimisation programme.

PMID- 21743072
TI  - Assessment of annual whole-body occupational radiation exposure in medical
      practice in Ghana (2000-09).
AB  - Occupational exposure to radiation in medical practice in Ghana has been analysed
      for a 10-y period between 2000 and 2009. Monitored dose data in the medical
      institution in Ghana from the Radiation Protection Institute's database were
      extracted and analysed in terms of three categories: diagnostic radiology,
      radiotherapy and nuclear medicine. One hundred and eighty medical facilities were
      monitored for the 10-y period, out of which ~98% were diagnostic radiology
      facilities. Only one nuclear medicine and two radiotherapy facilities have been
      operational in the country since 2000. During the 10-y study period, monitored
      medical facilities increased by 18.8%, while the exposed workers decreased by
      23.0%. Average exposed worker per entire medical institution for the 10-y study
      period was 4.3. Annual collective dose received by all the exposed workers
      reduced by a factor of 4 between 2000 and 2009. This is seen as reduction in
      annual collective doses in diagnostic radiology, radiotherapy and nuclear
      medicine facilities by ~76, ~72 and ~55%, respectively, for the 10-y period.
      Highest annual collective dose of 601.2 man mSv was recorded in 2002 and the
      least of 142.6 man mSv was recorded in 2009. Annual average values for dose per
      institution and dose per exposed worker decreased by 79 and 67.6%, respectively
      between 2000 and 2009. Average dose per exposed worker for the 10-y period was
      least in radiotherapy and highest in diagnostic radiology with values 0.14 and
      1.05 mSv, respectively. Nuclear medicine however recorded average dose per worker
      of 0.72 mSv. Correspondingly, range of average effective doses within the
      diagnostic radiology, radiotherapy and nuclear medicine facilities were 0.328
      2.614, 0.383-0.728 and 0.448-0.695 mSv, respectively. Throughout the study
      period, an average dose per medical institution of 3 mSv and an average dose per
      exposed worker of 0.69 mSv were realised. Exposed workers in diagnostic radiology
      primarily received most of the individual annual doses >1 mSv. The entire study
      period had 705 instances in which exposed workers received individual annual
      doses >1 mSv. On thermoluminescent dosemeter (TLD) return rates, facilities in
      Volta and Eastern Regions recorded highest return rates of 94.3% each. Ashanti
      Region recorded the least TLD return rate with 76.7%.

PMID- 21743073
TI  - Reducing the absorbed dose in analogue radiography of infant chest images by
      improving the image quality, using image processing techniques.
AB  - Radiographic inspection is one of the most widely employed techniques for medical
      testing methods. Because of poor contrast and high un-sharpness of radiographic
      image quality in films, converting radiographs to a digital format and using
      further digital image processing is the best method of enhancing the image
      quality and assisting the interpreter in their evaluation. In this research work,
      radiographic films of 70 infant chest images with different sizes of defects were
      selected. To digitise the chest images and employ image processing the two
      algorithms (i) spatial domain and (ii) frequency domain techniques were used. The
      MATLAB environment was selected for processing in the digital format. Our results
      showed that by using these two techniques, the defects with small dimensions are
      detectable. Therefore, these suggested techniques may help medical specialists to
      diagnose the defects in the primary stages and help to prevent more repeat X-ray
      examination of paediatric patients.

PMID- 21743074
TI  - Patient and endoscopist radiation doses during ERCP procedures.
AB  - The aim of the study was to calculate radiation doses for patients and staff
      during interventional Endoscopic retrograde cholangiopancreatography (ERCP)
      procedures. Patient age (A), kerma-area product (KAP), fluoroscopy time (T) and
      total number of films (F) were collected for 157 interventional ERCP procedures.
      One endoscopist (>10 y of experience) monitored using a thermoluminescent
      dosemeter worn over the lead apron performed the ERCPs. Median (range) KAP was
      3.1 Gy cm(-2) (0.1-106.7 Gy cm(-2)). Median (range) A, T and F were 72 y, 2.6
      (0.2-26.0) min and 2 (1-4) images, respectively. No correlation was observed
      between KAP and A, T or F. Monthly endoscopist dose was negligible due to the use
      of lead apron, collar and two lead-articulated ceiling mounted shields. The
      endoscopist dose is minimal when using appropriate protective measures. Patient
      doses showed large variation that has to be further investigated.

PMID- 21743075
TI  - Quality control and patient doses in X-ray computed tomography.
AB  - Results of quality control (QC) tests for a period of over a year and patient
      doses were analysed for several computed tomography units in our centre. The
      results of the QC tests were generally within limits for all of the examined
      scanners, proving good and stable performance of the systems. The tests were not
      helpful in predicting breakdowns of the systems such as tube failure. The doses
      for the same anatomical areas differed between scanners and in some cases
      exceeded the diagnostic reference levels (DRLs). DRLs are defined for typical
      diagnostic examinations performed in general hospitals and are not directly
      applicable to the examinations performed in the oncological centre.

PMID- 21743076
TI  - Approaches to promotion and implementation of action on Radiation Protection for
      children.
AB  - The Radiation Protection in Medicine conference, reviewed in this journal
      supplement, outlined nine strategies to promote radiation protection for
      patients. The Alliance for Radiation Safety in Pediatric Imaging has focused its
      work on three of those areas: creating awareness of the need and opportunities
      for radiation protection for children; developing open-source educational
      materials for medical professionals and parents on this critical topic for
      improved patient safety and communication; and lastly, advocating on behalf of
      children with industry, government and regulatory bodies to improve equipment
      design and safety features, standardisation of nomenclature and displays of dose
      reports across vendor platforms that reflect the special considerations of
      children.

PMID- 21743077
TI  - Radiation doses to patients undergoing enteroclysis.
AB  - Enteroclysis is a minimally invasive radiographic examination of the small
      intestine. During the procedure, considerable radiation dose is delivered to the
      patients. This study intends to: (a) evaluate the radiation dose to the patient
      using thermoluminescent dosemeters (TLDs, according to the protocol used at
      Radiology Department, University Hospital of Larissa, Greece; (b) estimate the
      thyroid surface dose (TSD) and doses to some radiosensitive organs located in the
      irradiation field. A total of 46 patients was examined. Patients were divided
      into two groups according to the digital X-ray machine used. The mean entrance
      surface dose (ESD) was 601.2 +/- 96.2 mGy and the mean fluoroscopy time was 8.5
      +/- 3 min, while the mean TSD was 0.34 +/- 0.6 mGy. The ESD for group A was lower
      by 20 % than group B due to fluoroscopic mode used. The dose values were higher
      than those in the literature. A local diagnostic reference level was introduced
      for further patient dose optimisation.

PMID- 21743078
TI  - Image quality and patient dose in computed tomography examinations in Greece.
AB  - The purpose of this study is to evaluate image quality of various computed
      tomography (CT) scanners installed in Greece, as well as to investigate patient
      doses from common CT examinations. An image quality survey was performed in 44 CT
      scanners countrywide. The imaging performance of the systems was evaluated by
      measurements of certain parameters, such as image noise, spatial uniformity, high
      and low-contrast resolution and slice thickness accuracy. Moreover, preliminary
      results of patient dose survey are presented. Concerning image quality, 80 % of
      the scanners were found to be in compliance with the national legislation and
      relative international guidelines for all the examined parameters. Weighted CT
      dose index and dose-length product values for chest and abdomen routine
      examinations were generally below the dose reference levels (DRLs) suggested by
      the European Commission. However, some scanners were found to deliver
      significantly higher doses than the suggested DRL for head routine examinations.
      Finally, differences in the performance among scanners of the same type and
      similar age were observed, pointing out the importance of frequent calibration,
      routine quality control and proper maintenance.

PMID- 21743079
TI  - Evaluation of organ doses in CT examinations with an infant anthropomorphic
      phantom.
AB  - The aim of this study is to evaluate organ doses in infant CT examinations with
      multi-detector row CT scanners. Radiation doses were measured with
      radiophotoluminescence glass dosemeters set in various organ positions within a 1
      y-old child anthropomorphic phantom and organ doses were evaluated from the
      measurement values. Doses for tissues or organs within the scan range were 28-36
      mGy in an infant head CT, 3-11 mGy in a chest CT, 5-11 mGy in an abdominal-pelvic
      CT and 2-14 mGy in a cardiac CT. The doses varied by the differences in the types
      of CT scanners and scan parameters used at each medical facility. Compared with
      those for children of various ages, the doses in an infant CT protocol were found
      to be similar to or slightly smaller than those in a paediatric CT for 5- or 6-y
      old children.

PMID- 21743080
TI  - Assessment of effective dose in paediatric CT examinations.
AB  - Current concerns focus on the high doses encountered in computed tomography (CT)
      examinations as they are extending towards younger and more radiosensitive
      patients. Previous work produced conversion coefficients for effective dose (E)
      from dose-length product (DLP) for four anatomical body regions applicable to any
      patient size. This work aims to update the earlier work, incorporating the new
      ICRP 2007 tissue-weighting factors and testing the methodology on modern
      scanners. For each age and body region, E was determined relative to DLP.
      Measurements were carried out on a 64-slice scanner to test this methodology. The
      conversion coefficients show exponential decrease with patient size. Conversion
      factors for the pelvis region are lower than before (30-40 %), those for the
      chest increased (by up to 25 %) whereas those for the head and abdomen remained
      fairly similar. Application of the coefficients to modern scanners verified the
      results, so that this methodology can be applied for a wide range of paediatric
      CT examinations.

PMID- 21743081
TI  - Level of compliance with the radiation protection regulation--a survey among
      Norwegian hospitals and X-ray institutes.
AB  - To identify the level of compliance with the new radiation protection regulation
      among Norwegian health care enterprises (HCEs). Totally, 41 HCEs were authorised
      to use advanced X-ray equipment for medical purposes during 2005-07. Follow-up
      inspections with 14 HCEs were carried out during 2007-09. Main topics for the
      inspections were those requirements identified as most challenging to implement
      in the authorisation process. Totally, 192 non-conformities with the regulation
      were revealed during the authorisation process. The inspections revealed that 93
      % of the inspected HCEs had non-conformities with the regulation. Most common non
      conformities dealt with skills in radiation protection, establishment of local
      diagnostic reference levels, access to medical physicists and performance of
      quality control of X-ray equipment. Inspections are an effective tool for
      implementation of regulation the requirements at the HCEs, thus improving
      radiation protection awareness.

PMID- 21743082
TI  - Exposure to patient during interventional endourological procedures.
AB  - The purpose of this work is to study doses to patients undergoing interventional
      endourological procedures. The study was performed in a modern Clinic of
      Endourology and Shockwave Lithotripsy, equipped with two dedicated X-ray systems.
      The following information was recorded for each patient: type of the procedure,
      patient age, fluoroscopy time, number of images acquired and patient dose in air
      kerma-area product, P(KA), measured with KAP-meters integrated in the X-ray
      units. Eleven types of procedures were included. From the collected sample of 429
      patients for all procedures, the mean fluoroscopy time varied between 0.2 and 4
      min. The highest values of mean P(KA) 457 and 590 cGy cm(2) were found for
      percutaneous nephrolithotripsy and ureteroscopy, respectively. The mean values of
      P(KA) for rest of the procedures investigated were between 58 and 398 cGy cm(2).
      Individual patient doses varied between 2 and 2440 cGy cm(2) and fluoroscopy time
      -between 0.1 and 13.7 min. The first study in interventional endourology in
      Bulgaria demonstrated big variations in patient doses depending on the type and
      the complexity of procedure, operator's experience and exposure modes.

PMID- 21743083
TI  - Fatal cowpox virus infection in two squirrel monkeys (Saimiri sciureus).

PMID- 21743084
TI  - Sequence determinants for the tandem recognition of UGU and CUG rich RNA elements
      by the two N--terminal RRMs of CELF1.
AB  - CUGBP, Elav-like family member 1 (CELF1) is an RNA binding protein with important
      roles in the regulation of splicing, mRNA decay and translation. CELF1 contains
      three RNA recognition motifs (RRMs). We used gel retardation, gel filtration,
      isothermal titration calorimetry and NMR titration studies to investigate the
      recognition of RNA by the first two RRMs of CELF1. NMR shows that RRM1 is
      promiscuous in binding to both UGU and CUG repeat sequences with comparable
      chemical shift perturbations. In contrast, RRM2 shows greater selectivity for
      UGUU rather than CUG motifs. A construct (T187) containing both binding domains
      (RRM1 and RRM2) was systematically studied for interaction with tandem UGU RNA
      binding sites with different length linker sequences UGU(U)(x)UGU where x = 1-7.
      A single U spacer results in interactions only with RRM1, demonstrating both
      steric constraints in accommodating both RRMs simultaneously at adjacent sites,
      and also subtle differences in binding affinities between RRMs. However, high
      affinity co-operative binding (K(d) ~ 0.4 uM) is evident for RNA sequences with x
      = 2-4, but longer spacers (x >= 5) lead to a 10-fold reduction in affinity. Our
      analysis rationalizes the high affinity interaction of T187 with the 11mer GRE
      consensus regulatory sequence UGUUUGUUUGU and has significant consequences for
      the prediction of CELF1 binding sites.

PMID- 21743085
TI  - Transcriptomes of the anther sporophyte: availability and uses.
AB  - An anther includes sporophytic tissues of three outer cell layers and an
      innermost layer, the tapetum, which encloses a locule where the gametophytic
      microspores mature to become pollen. The sporophytic tissues also comprise some
      vascular cells and specialized cells of the stomium aligning the long anther axis
      for anther dehiscence. Studies of the anther sporophytic cells, especially the
      tapetum, have recently expanded from the use of microscopy to molecular biology
      and transcriptomes. The available sequencing technologies, plus the use of laser
      microdissection and in silico subtraction, have produced high-quality anther
      sporophyte transcriptomes of rice, Arabidopsis and maize. These transcriptomes
      have been used for research discoveries and have potential for future discoveries
      in diverse areas, including developmental gene activity networking and changes in
      enzyme and metabolic domains, prediction of protein functions by quantity,
      secretion, antisense transcript regulation, small RNAs and promoters for
      generating male sterility. We anticipate that these studies with rice and other
      transcriptomes will expand to encompass other plants, whose genomes will be
      sequenced soon, with ever-advancing sequencing technologies. In comprehensive
      gene activity profiling of the anther sporophyte, studies involving
      transcriptomes will spearhead investigation of the downstream gene activity with
      proteomics and metabolomics.

PMID- 21743086
TI  - Quality appraisal of clinical practice guidelines on the use of physiotherapy in
      rheumatoid arthritis: a systematic review.
AB  - OBJECTIVE: To assess the quality of guidelines published in peer-reviewed
      literature concerning the role of physiotherapy in the management of patients
      with RA. METHODS: A systematic literature search for clinical practice guidelines
      that included physiotherapy interventions was performed in four electronic
      databases. We assessed the quality of the selected guidelines using the appraisal
      of guidelines for research and evaluation (AGREE) instrument. In addition, the
      recommendations of guidelines with the highest quality scores were summarized.
      RESULTS: Eight clinical practice guidelines fulfilled the inclusion criteria.
      Scope/purpose was the most often adequately addressed AGREE domain (in seven of
      the eight guidelines) and applicability the least (in two of the eight
      guidelines). Based on the AGREE domain scores, six guidelines could be
      recommended or strongly recommended for clinical use. Five out of these six
      (strongly) recommended guidelines included a recommendation on exercise therapy
      and/or patient education, with these interventions being recommended in every
      case. Transcutaneous electrical nerve stimulation and thermotherapy were
      recommended in four of these six guidelines. US, thermotherapy, low-level laser
      therapy, massage, passive mobilization and balneotherapy were addressed in one or
      two of these six guidelines. CONCLUSION: Six of eight clinical practice
      guidelines addressing physiotherapy interventions were recommended or strongly
      recommended according to the AGREE instrument. In general, guideline
      recommendations on physiotherapy intervention, from both the recommended
      guidelines as well as from the not recommended guidelines, lacked detail
      concerning mode of delivery, intensity, frequency and duration.

PMID- 21743087
TI  - Cardiovascular education for people with rheumatoid arthritis: what can existing
      patient education programmes teach us?
AB  - Patient education is an integral component of the management of chronic diseases.
      Education programmes designed for people with RA have historically aimed to
      improve their arthritis symptoms and outcomes. Novel educational material is
      required to address significant comorbidities, particularly cardiovascular
      disease (CVD) associated with RA. We appraise the components of education
      programmes incorporated in disease management in people with RA and programmes
      used for CVD prevention in the general population, including their design and
      delivery, use of behaviour theory, evaluation and long-term efficacy. We then
      integrate the findings in order to inform the development of educational material
      specifically addressing CVD in RA. This approach may be useful for other major
      comorbidities of RA as well as other musculoskeletal conditions.

PMID- 21743088
TI  - Longitudinal levels of apolipoproteins and antibodies against phosphorylcholine
      are independently associated with carotid artery atherosclerosis 5 years after
      rheumatoid arthritis onset--a prospective cohort study.
AB  - OBJECTIVE: RA is associated with premature atherosclerosis. Here, we determined
      the associations of apolipoproteins and immunoglobulin M (IgM) antibodies against
      phosphorylcholine (anti-PC) with carotid artery atherosclerosis in a prospective
      cohort of patients with early RA. METHODS: In all 114 patients, age 50.6 (11.2)
      years, 68.4% women, with recent RA (<12 months after symptoms onset) were
      included and assessed at 0, 3, 12, 24 and 60 months after RA diagnosis. At the
      same time points, apolipoproteins were determined by immunoturbidimetry, and IgM
      anti-PC by ELISA. Carotid intima-media thickness (cIMT) (common carotid) and
      occurrence of plaques (common, internal and external carotids) were the principal
      study outcomes, which were examined with high-resolution B-mode ultrasonography
      after 5 years of RA disease. Mixed linear modelling and generalized estimating
      equations (GEEs) were used for longitudinal statistical analyses. RESULTS:
      Multivariate regression analyses showed that age, male gender, smoking (ever) and
      history of cardiovascular disease (CVD), hypertension or diabetes mellitus, but
      no other baseline variables, had independent associations with cIMT (P < 0.05).
      Plaque detection was positively associated with age and smoking (ever). After
      adjustment, a longitudinal approach demonstrated an independent negative
      prediction of cIMT by apoA1 (P = 0.047), but a positive by apoB/apoA1 ratio (P =
      0.030). Higher levels of pro-atherogenic apolipoproteins over time, apoB and
      apoB/apoA1 ratio, and low anti-PC tertile were independently associated with
      enhanced detection of bilateral carotid plaque (P = 0.002, 0.026 and 0.000,
      respectively). Both baseline and longitudinal levels of inflammatory/disease
      related factors failed to show significant associations with the study outcomes.
      CONCLUSION: Apolipoproteins and anti-PC may have independent roles in subclinical
      atherosclerosis in patients with RA.

PMID- 21743089
TI  - Flexibility in the patterning and control of axial locomotor networks in lamprey.
AB  - In lower vertebrates, locomotor burst generators for axial muscles generally
      produce unitary bursts that alternate between the two sides of the body. In
      lamprey, a lower vertebrate, locomotor activity in the axial ventral roots of the
      isolated spinal cord can exhibit flexibility in the timings of bursts to dorsally
      located myotomal muscle fibers versus ventrally-located myotomal muscle fibers.
      These episodes of decreased synchrony can occur spontaneously, especially in the
      rostral spinal cord where the propagating body waves of swimming originate.
      Application of serotonin, an endogenous spinal neurotransmitter known to
      presynaptically inhibit excitatory synapses in lamprey, can promote decreased
      synchrony of dorsal-ventral bursting. These observations suggest the possible
      existence of dorsal and ventral locomotor networks with modifiable coupling
      strength between them. Intracellular recordings of motoneurons during locomotor
      activity provide some support for this model. Pairs of motoneurons innervating
      myotomal muscle fibers of similar ipsilateral dorsoventral location tend to have
      higher correlations of fast synaptic activity during fictive locomotion than do
      pairs of motoneurons innervating myotomes of different ipsilateral dorsoventral
      locations, suggesting their control by different populations of premotor
      interneurons. Further, these different motoneuron pools receive different
      patterns of excitatory and inhibitory inputs from individual reticulospinal
      neurons, conveyed in part by different sets of premotor interneurons. Perhaps,
      then, the locomotor network of the lamprey is not simply a unitary burst
      generator on each side of the spinal cord that activates all ipsilateral body
      muscles simultaneously. Instead, the burst generator on each side may comprise at
      least two coupled burst generators, one controlling motoneurons innervating
      dorsal body muscles and one controlling motoneurons innervating ventral body
      muscles. The coupling strength between these two ipsilateral burst generators may
      be modifiable and weakening when greater swimming maneuverability is required.
      Variable coupling of intrasegmental burst generators in the lamprey may be a
      precursor to the variable coupling of burst generators observed in the control of
      locomotion in the joints of limbed vertebrates.

PMID- 21743090
TI  - Plasma beta-2 microglobulin as a marker of frailty in older adults: a pilot
      study.

PMID- 21743091
TI  - Evaluation of the sustained effect of inpatient falls prevention education and
      predictors of falls after hospital discharge--follow-up to a randomized
      controlled trial.
AB  - BACKGROUND: This study aimed to determine (i) risk factors for postdischarge
      falls and (ii) the effect of inpatient falls prevention education on rates of
      falls after discharge. METHODS: Participants (n = 343) were a prospective cohort
      nested within a randomized controlled trial (n = 1,206) of falls prevention
      patient education in hospital compared with usual care. Participants were
      followed up for 6 months after discharge and falls recorded via a falls diary and
      monthly telephone calls. Potential falls risk factors were assessed at point of
      discharge and at 6 months postdischarge using a telephone survey. RESULTS: There
      were 276 falls among 138 (40.2%) participants in the 6 months following discharge
      (4.52/1,000 person days) of which 150 were injurious falls (2.46/1,000 person
      days). Pairwise comparisons found no significant differences between groups in
      rates of falls after adjustment for confounding variables. Independent risk
      factors for all falls outcomes were male gender, history of falls prior to
      hospital admission, fall during hospital admission, depressed mood at discharge,
      using a walking aid at discharge, and receiving assistance with activities of
      daily living at 6 months following discharge. Receiving assistance with
      activities of daily living significantly reduced the risk of falls and injurious
      falls for high risk patients. CONCLUSIONS: Older patients are at increased risk
      of falls and falls injuries following discharge. Education that effectively
      reduced inpatient falls appears to have no ongoing protective effect after
      discharge. Independent risk factors for falls in this population differ from both
      hospital and general community settings.

PMID- 21743092
TI  - Exploring biologically relevant pathways in frailty.
AB  - BACKGROUND: Frailty is a late-life syndrome of vulnerability to adverse health
      outcomes characterized by a phenotype that includes muscle weakness, fatigue, and
      inflammatory pathway activation. The identification of biologically relevant
      pathways that influence frailty is challenged by its biological complexity and
      the necessity in separating disease states from the syndrome of frailty. As with
      longevity research, genetic analyses may help to provide insights into
      biologically relevant pathways that contribute to frailty. METHODS: Based on
      current understanding of the physiological basis of frailty, we hypothesize that
      variation in genes related to inflammation and muscle maintenance would associate
      with frailty. One thousand three hundred and fifty-four single-nucleotide
      polymorphisms were genotyped across 134 candidate genes using the Illumina
      Genotyping platform, and the rank order by strength of association between
      frailty and genotype was determined in a cross-sectional study. RESULTS: Although
      no single-nucleotide polymorphism reached study-wide significance after
      controlling family-wise false-discovery rate at 0.05, single-nucleotide
      polymorphisms within the 5-methyltetrahydrofolate-homocysteine methyltransferase
      (MTR), Caspase 8 (CASP8), CREB-binding protein (CREBBP), lysine acetyltransferase
      2B (KAT2B), and beta-transducin repeat containing (BTRC) loci were among those
      strongly associated with frailty. CONCLUSIONS: The apoptosis- and transcription
      regulation-related pathways highlighted by this preliminary analysis were
      consistent with prior gene expression studies in a frail mouse model and provide
      useful etiological insights for future biological studies of frailty.

PMID- 21743093
TI  - Race, socioeconomic resources, and late-life mobility and decline: findings from
      the Health, Aging, and Body Composition study.
AB  - BACKGROUND: This study examines the relationship between race and mobility over 5
      years in initially well-functioning older adults and evaluates how a broad set of
      socioeconomic status indicators affect this relationship. METHODS: Data were from
      2,969 black and white participants aged 70-79 from the Health, Aging, and Body
      Composition study. Mobility parameters included self-reported capacity to walk a
      quarter mile and climb 10 steps and usual gait speed. Incident mobility
      limitation was defined as reported difficulty walking a quarter mile or climbing
      10 steps at two consecutive semiannual assessments. Gait speed decline was
      defined as a 4% reduction in speed per year. RESULTS: At baseline, even though
      all participants were free of mobility limitation, blacks had slower walking
      speed than their white counterparts, which was not explained by poverty,
      education, reading level, or income adequacy. After 5 years, accounting for age,
      site, and baseline mobility, blacks were more likely to develop mobility
      limitation than whites. Adjusting for prevalent conditions at baseline eliminated
      this difference in women; controlling for education eliminated this difference in
      men. No differences in gait speed decline were identified. CONCLUSIONS: Higher
      rates of mobility loss observed in older blacks relative to older whites appear
      to be a function of both poorer initial mobility status and existing health
      conditions particularly for women. Education may also play a role especially for
      men.

PMID- 21743094
TI  - Effect of chorda tympani nerve transection on salt taste perception in mice.
AB  - Effects of gustatory nerve transection on salt taste have been studied
      extensively in rats and hamsters but have not been well explored in the mouse. We
      examined the effects of chorda tympani (CT) nerve transection on NaCl taste
      preferences and thresholds in outbred CD-1 mice using a high-throughput
      phenotyping method developed in our laboratory. To measure taste thresholds, mice
      were conditioned by oral self-administration of LiCl or NaCl and then presented
      with NaCl concentration series in 2-bottle preference tests. LiCl-conditioned and
      control NaCl-exposed mice were given bilateral transections of the CT nerve (LiCl
      CTX, NaCl-CTX) or were left intact as controls (LiCl-CNT, NaCl-CNT). After
      recovery from surgery, mice received a concentration series of NaCl (0-300 mM) in
      48-h 2-bottle tests. CT transection increased NaCl taste thresholds in LiCl
      conditioned mice and eliminated avoidance of concentrated NaCl in control NaCl
      exposed mice. This demonstrates that in mice, the CT nerve is important for
      detection and recognition of NaCl taste and is necessary for the normal avoidance
      of high concentrations of NaCl. The results of this experiment also show that the
      method of high-throughput phenotyping of salt taste thresholds is suitable for
      detecting changes in the taste periphery in mouse genetic studies.

PMID- 21743095
TI  - Sweetness intensity enhancement by pulsatile stimulation: effects of magnitude
      and quality of taste contrast.
AB  - Upon stimulation with continuously alternating (pulsatile) taste concentrations,
      humans report higher average taste intensities than for continuous stimulation
      with the same average tastant concentration. We investigated the effect of the
      magnitude of concentration changes (concentration contrast) and the effect of
      taste quality changes (quality contrast) between alternating tastants on sweet
      taste enhancement. The perceived sweetness intensity increased with the magnitude
      of the sucrose concentration contrast: The pulsatile stimulus with the highest
      concentration difference (average sucrose concentration: 60 g/L) was rated as the
      sweetest in spite of the fact that the gross sucrose concentrations were
      identical over stimuli. Moreover, this stimulus was rated equally sweet as a
      continuous reference of 70 g/L sucrose. On alternation of sucrose with the
      qualitatively different citric acid, sweet taste enhancement remained at the
      level observed for alternation with water at citric acid concentration levels up
      to 3 times its detection threshold. Alternation of a sucrose solution with a
      citric acid solution at 9 times its threshold concentration, resulted in an
      attenuation of the pulsation-induced enhancement effect. Upon alternation of
      citric acid pulses at concentrations around the threshold with water intervals
      only, no taste enhancement was observed compared with continuous citric acid
      stimuli of the same net concentration. We propose that the magnitude of pulsation
      induced taste enhancement is determined by the absolute rather than relative
      change of tastant concentration. This explains why 1) pulsation-induced sweet
      taste enhancement is determined by the magnitude of the sucrose pulse-interval
      contrast and 2) the alteration of citric acid with water does not enhance taste
      intensity at detection threshold level.

PMID- 21743096
TI  - Chemosensory exploration of male scent by female rock lizards result from
      multiple chemical signals of males.
AB  - Multiple sexual signals may convey information on males' quality. However, most
      research focused on visual signals, ignoring chemical signals. In vertebrates,
      chemical signals are probably often a multicomponent mixture of several active
      compounds, but they are not well known. We examined the potential additive and
      interactive effects of 2 compounds (oleic acid and ergosterol) naturally found in
      femoral gland secretions of male rock lizards on chemosensory exploration
      behavior of females. Tongue-flick (TF) rates of females to male secretions may
      result from the combination of responses to multiple compounds. There may be an
      additive or synergetic effect because male secretions with the highest
      proportions of both compounds received the highest TF rates, suggesting that
      their scents were more intriguing. However, there might be an interactive effect
      too; female TF rates were higher to males' scent with high proportions of
      ergosterol alone, even if proportions of oleic acid were low, than to high
      proportions of oleic acid but with low proportions of ergosterol. Further
      bioassays testing TF behavior of females to standard compounds, presented alone
      or combined in different concentrations confirmed these findings. Variations in
      female TF behavior might be explained because different compounds signal
      different male traits of different importance for females. Our study suggested
      that femoral secretion of male rock lizards may act as a multicomponent chemical
      signal.

PMID- 21743097
TI  - Vestibular inputs to human motion-sensitive visual cortex.
AB  - Two crucial sources of information available to an organism when moving through
      an environment are visual and vestibular stimuli. Macaque cortical area MSTd
      processes visual motion, including cues to self-motion arising from optic flow
      and also receives information about self-motion from the vestibular system. In
      humans, whether human MST (hMST) receives vestibular afferents is unknown. We
      have combined 2 techniques, galvanic vestibular stimulation and functional MRI
      (fMRI), to show that hMST is strongly activated by vestibular stimulation in
      darkness, whereas adjacent area MT is unaffected. The activity cannot be
      explained in terms of somatosensory stimulation at the electrode site. Vestibular
      input appears to be confined to the anterior portion of hMST, suggesting that
      hMST as conventionally defined may contain 2 subregions. Vestibular activity was
      also seen in another area previously implicated in processing visual cues to self
      motion, namely the cingulate sulcus visual area (CSv), but not in visual area V6.
      The results suggest that cross-modal convergence of cues to self-motion occurs in
      both hMST and CSv.

PMID- 21743098
TI  - Reciprocal imitation: toward a neural basis of social interaction.
AB  - Social interaction is a coregulated coupling activity that involves at least 2
      autonomous agents. Numerous methodological and technical challenges impede the
      production of natural social interaction within an Magnetic Resonance Imaging
      environment under controlled conditions. To overcome the obstacle, we chose a
      simple format of social interaction, namely "interactive imitation" through a
      double-video system. We registered blood oxygen level-dependent activity of 23
      participants during 2 imitative conditions: free (F) and instructed (I) episodes
      of imitating (i) and of being imitated (bi). In addition to the areas classically
      reported in instructed imitation tasks, 2 activation patterns were found, which
      differentiate the subconditions. Firstly, brain areas involved during decisional
      and attentional processes (dorsolateral prefrontal cortex , dorsal part of
      anterior cingulate gyrus [dACC], pre-SMA) were activated during all conditions
      except for instructed imitation-classically used in neuroimaging studies of
      imitation. Second, a greater activation in dACC and insula combined with an
      increased deactivation in the default mode network was observed when subjects
      were imitated compared with when they imitated. We suggest that these 2 patterns
      reflect the anticipation of the other's behavior and the engagement with others
      required by social interaction.

PMID- 21743103
TI  - Integration of physical and genetic maps in apple confirms whole-genome and
      segmental duplications in the apple genome.
AB  - A total of 355 simple sequence repeat (SSR) markers were developed, based on
      expressed sequence tag (EST) and bacterial artificial chromosome (BAC)-end
      sequence databases, and successfully used to construct an SSR-based genetic
      linkage map of the apple. The consensus linkage map spanned 1143 cM, with an
      average density of 2.5 cM per marker. Newly developed SSR markers along with 279
      SSR markers previously published by the HiDRAS project were further used to
      integrate physical and genetic maps of the apple using a PCR-based BAC library
      screening approach. A total of 470 contigs were unambiguously anchored onto all
      17 linkage groups of the apple genome, and 158 contigs contained two or more
      molecular markers. The genetically mapped contigs spanned ~421 Mb in cumulative
      physical length, representing 60.0% of the genome. The sizes of anchored contigs
      ranged from 97 kb to 4.0 Mb, with an average of 995 kb. The average physical
      length of anchored contigs on each linkage group was ~24.8 Mb, ranging from 17.0
      Mb to 37.73 Mb. Using BAC DNA as templates, PCR screening of the BAC library
      amplified fragments of highly homologous sequences from homoeologous chromosomes.
      Upon integrating physical and genetic maps of the apple, the presence of not only
      homoeologous chromosome pairs, but also of multiple locus markers mapped to
      adjacent sites on the same chromosome was detected. These findings demonstrated
      the presence of both genome-wide and segmental duplications in the apple genome
      and provided further insights into the complex polyploid ancestral origin of the
      apple.

PMID- 21743104
TI  - Circulating cancer cells in division in an early breast cancer patient.

PMID- 21743105
TI  - Implementation and dissemination research: the time has come!

PMID- 21743106
TI  - A-z of nutritional supplements: dietary supplements, sports nutrition foods and
      ergogenic aids for health and performance--part 23.

PMID- 21743108
TI  - Asthma Training Module (ATM), Asthma by Consensus (ABC) and asthma education.

PMID- 21743107
TI  - Progeria, rapamycin and normal aging: recent breakthrough.
AB  - A recent discovery that rapamycin suppresses a pro-senescent phenotype in
      progeric cells not only suggests a non-toxic therapy for progeria but also
      implies its similarity with normal aging. For one, rapamycin is also known to
      suppress aging of regular human cells. Here I discuss four potential scenarios,
      comparing progeria with both normal and accelerated aging. This reveals further
      indications of rapamycin both for accelerated aging in obese and for progeria.

PMID- 21743109
TI  - Neonatal intensive care practices harmful to the developing brain.
AB  - There has been a marked increase in the survival of extremely low birth weight
      (ELBW) infants, but these babies have a long stay in the NICU. Strategies to
      decrease their neurodevelopmental impairment become very important. The maximum
      development of the brain occurs between 29-41 weeks. From the warm, dark,
      acquatic econiche, where the baby hears pleasant sounds like the mother's heart
      beat, the baby suddenly finds itself in the dry, cold, excessively bright, noisy,
      environment of the NICU. Noise, bright light, painful procedures, and ill-timed
      caregiving activities, adversely affect the infant's development. Excessive
      radiation from X-rays of babies on the ventilator and CT scans also affect the
      brain. Medications like steroids for chronic lung disease also cause damage to
      the brain. Aminoglycides and frusemide are known to cause hearing impairment.
      Hence a developmentally supportive, humanized care will go a long way in
      enhancing the developmental outcome of these babies.

PMID- 21743110
TI  - Brain cooling in babies: are we ready for clinical trials in developing
      countries?

PMID- 21743111
TI  - Continuation of high goiter prevalence in regions with successful salt iodization
      program.

PMID- 21743113
TI  - DOOR syndrome.
AB  - DOOR syndrome is a rare multisystem genetic disorder, consisting of deafness
      (sensorineural), onychodystrophy, osteodystrophy, and mental retardation.
      Seizures reported frequently in this condition are often refractory to treatment.

PMID- 21743112
TI  - Holoprosencephaly: a guide to diagnosis and clinical management.
AB  - CONTEXT: Holoprosencephaly affects 1 in 8,000 live births and is the most common
      structural anomaly of the developing forebrain, resulting in facial dysmorphism,
      neurologic impairment, and additional clinical sequelae. Given the increasing
      relative contribution of genetic diseases to perinatal morbidity and mortality in
      India, proper recognition and management of holoprosencephaly can improve care
      for a significant number of affected Indian children. EVIDENCE ACQUISITION: We
      used the PubMed database (search terms: "holoprosencephaly," "HPE,"
      "holoprosencephaly India") and cross-referenced articles regarding
      holoprosencephaly, using our research group's extensive experience as a guide for
      identifying seminal papers in the field. RESULTS: Holoprosencephaly is classified
      into four types based on the nature of the brain malformations as seen on
      neuroimaging and/or pathologic examination, with typically recognizable
      craniofacial phenotypes. Despite the identification of several genetic loci and
      other etiologic agents involved in pathogenesis, additional causes are elusive.
      Moreover, satisfactory explanations for phenomena such as incomplete penetrance
      and variable expressivity are lacking. CONCLUSIONS: For each patient,
      pediatricians should follow a diagnostic protocol including dysmorphology
      examination, complete family history and ascertainment of risk factors, and
      neuroimaging. Many medical issues, including hypothalamic dysfunction,
      endocrinologic dysfunction, motor impairment, respiratory issues, seizures, and
      hydrocephalus should be prioritized in management. Pediatricians should work with
      genetic specialists to identify syndromic forms and to perform cytogenetic
      investigation, molecular screening, and genetic counseling in order to fully
      characterize prognosis and recurrence risk.

PMID- 21743114
TI  - Numb chin syndrome in acute lymphoblastic leukemia.
AB  - Numb chin syndrome is a sensory neuropathy of the inferior alveolar branch of the
      trigeminal nerve, characterized by unilateral numbness of the chin, the lower lip
      and the buccal and gingival mucosa. We report a girl with acute lymphoblastic
      leukemia of B-cell type who initially presented with numb chin syndrome resulting
      from skull base infiltration.

PMID- 21743115
TI  - Hopkins syndrome and phantom hernia: a rare association.
AB  - Acute flaccid paralysis (AFP), other than paralytic poliomyelitis, are usually
      due to demyelination like Guillian Barre syndrome (GBS), transverse myelitis and
      traumatic neuritis. Poliomyelitis like illness, Hopkins syndrome or Post
      Asthmatic Amotrophy, associated with bronchial asthma and hyperIgEemia has been
      reported in literature. We present a two and a half year old child who developed
      AFP with phantom hernia following an episode of bronchial asthma.

PMID- 21743116
TI  - Prolonged cholestasis due to hepatitis A virus infection.
AB  - We present a 12-year old boy with jaundice for 2 weeks. The child was deeply
      icteric and had hepatomegaly. IgM antibodies for hepatitis A virus were positive.
      However this child had prolonged cholestasis and cholestyramine was started. The
      child responded only after prednisolone was started.

PMID- 21743117
TI  - Peak expiratory flow rate among child labourers in West Bengal, India.
AB  - This study was conducted to evaluate Peak expiratory flow rate (PEFR) in
      different groups of working children. Study population comprises of 300 child
      workers, 100 in each group (agricultural workers, constructional workers, control
      group or domestic workers with equal sex, age and socioeconomic distribution).
      PEFR value was lowest among construction workers. PEFR values of all subjects had
      a linear relationship with age, weight, and height.

PMID- 21743118
TI  - Assessment of nutritional status of rural tribal children in Tripura.
AB  - This cross-sectional study evaluated the nutritional status of 608 rural tribal
      children (age 6 to 15 years) from Jampuijala block of West Tripura district,
      India. Prevalence of stunting, thinness and overweight were 23.7%, 33.4% and
      0.8%, respectively. The prevalence of stunting and thinness was found to be
      higher in boys than in girls.

PMID- 21743119
TI  - Negative studies published in Indian medical journals are underpowered.
AB  - 51 inconclusive studies published in 14 Indian medical journals were analyzed for
      adequacy of power by post hoc power calculation. No study was found to be
      adequately powered (%80%) at small effect size, only 8 studies were adequately
      powered for medium effect size and 30 studies were adequately powered at large
      effect size.

PMID- 21743120
TI  - Profile of acute renal failure in children in Kashmir.
AB  - We report on the etiology and the short term outcome (3 month) of children with
      acute renal failure (ARF) at a tertiary care centre in north India. Acute tubular
      necrosis was the commonest cause of ARF (33%) especially in children <5 years of
      age; while in children >10 years, glomerulonephritis was the commonest cause. The
      overall mortality rate was 20%.The outcome at 3 months showed normal renal
      function in 72 patients and CKD in 5 patients. Three patients were lost to follow
      up.

PMID- 21743121
TI  - Tailor-made three-dimensional hybrid scaffolds for cell cultures.
AB  - The construction of the ideal three-dimensional scaffold for cell culture is one
      of the most intriguing topics in tissue engineering. It has been shown that cells
      can be cultured on most organic biomimetic materials, which now are losing
      popularity in favour of novel, hybrid systems. In this study, a series of
      photosensitive sol-gel hybrid materials, based on silicon-zirconium and silicon
      titanium oxides, have been investigated for their suitability in three
      dimensional scaffold fabrication. These materials can be structured by two-photon
      polymerization, a laser-based technique allowing the fabrication of micrometre
      size structures with submicron resolution. The work presented here examined the
      effect of the organic/inorganic composition of the materials on cell behaviour
      and the establishment of a 'cell-culture friendly' environment. This is vital for
      cell adhesion, growth and differentiation, as the organic part of the material
      provides the soft matrix for cell growth, whereas the inorganic component gives
      the mechanical stability and rigidity of the three-dimensional structures. In
      addition, the use of femtosecond laser structuring permits the fabrication of a
      wide range of mechanically stable scaffolds of different sizes and shapes to be
      tested in terms of cell viability, proliferation and orientation.

PMID- 21743122
TI  - Comparative analysis of the isovolume calibration method for non-invasive
      respiratory monitoring techniques based on area transduction versus circumference
      transduction using the connected cylinders model.
AB  - An analytical formalism developed previously to examine the robustness of the
      isovolume calibration technique for non-invasive respiratory monitoring devices
      based on measurements of torso circumference (e.g. fibre-optic respiratory
      plethysmography) is extended here to techniques based on area measurement (e.g.
      respiratory inductive plethysmography), and the results are compared. The earlier
      perturbation approach is adopted, and an exact method is also presented. It is
      demonstrated that the area-based techniques have less dependence on the
      cylindrical compartmental parameters of radius and height, and are independent of
      compartmental volume if height variations are negligible, in contrast to
      circumference-based techniques. It is also demonstrated that both the area- and
      the circumference-based techniques provide similar inferences of volume when
      calibrated using the isovolume method under reasonable assumptions for the
      dimensions of the compartments that constitute a model of the torso.

PMID- 21743123
TI  - A dielectric inverse problem applied to human skin measurements during glucose
      excursions.
AB  - A fringing field capacitive sensor has been used to measure the dielectric
      properties of human skin and underlying tissue in the MHz frequency range. It has
      recently been shown in clinical experimental studies that these dielectric
      properties can be related to the effects of in vivo glucose variations of the
      test subject. Previously, the relationship between electrical impedance and the
      glucose level has been established via statistical methods, such as the
      regression method. In this work, we explored a different approach, namely the
      resolution of the so-called inverse problem. First we applied the method on an
      artificial two-layer lossy system in order to test the sensitivity of the
      solution to forced changes in the layer properties and its stability to a
      constant setting. After validation of this method on artificial systems, a
      similar inverse problem was set and solved for dielectric measurements on human
      skin during an induced glucose excursion, where the skin is also modelled as a
      double-layer system. The changes of the measured permittivity and conductivity of
      the second layer versus the glucose changes are calculated for 22 study days. The
      statistical distribution shows that the median slopes of both dielectric
      properties are negative. These results can be used to test our hypothesis and to
      continue building potential explanations for the phenomena induced by the glucose
      changes on the skin layer dielectric parameters.

PMID- 21743124
TI  - The conductivity of neonatal piglet skulls.
AB  - We report the first measured values of conductivities for neonatal mammalian
      skull samples. We measured the average radial (normal to the skull surface)
      conductivity of fresh neonatal piglet skull samples at 1 kHz and found it to be
      around 30 mS m(-1) at ambient room temperatures of about 23  degrees C.
      Measurements were made on samples of either frontal or parietal cranial bone,
      using a saline-filled cell technique. The conductivity value we observed was
      approximately twice the values reported for adult skulls (Oostendorp et al 2000
      IEEE Trans. Biomed. Eng. 47 1487-92) using a similar technique, but at a
      frequency of around 5 Hz. Further, we found that the conductivity of skull
      fragments increased linearly with thickness. We found evidence that this was
      related to differences in composition between the frontal and parietal bone
      samples tested, which we believe is because frontal bones contained a larger
      fraction of higher conductivity cancellous bone material.

PMID- 21743125
TI  - Modeling of hyaluronan clearance with application to estimation of lymph flow.
AB  - One of the important factors in blood pressure regulation is the maintenance of
      the level of blood volume, which depends on several factors including the rate of
      lymph flow. Lymph flow can be measured directly using cannulation of lymphatic
      vessels, which is not clinically feasible, or indirectly by the tracer appearance
      rate, which is the rate at which macromolecules appear into the blood from the
      peritoneal cavity. However, indirect lymph flow measurements do not always
      provide consistent results. Through its contribution to osmotic pressure and
      resistance to flow, the macromolecule hyaluronan takes part in the regulation of
      tissue hydration and the maintenance of water and protein homeostasis. It arrives
      in blood plasma through lymph flow. Lymphatic hyaluronic acid (HA, hyaluronan)
      concentration is several times higher than that in plasma, suggesting that the
      lymphatic route may account for the majority of HA found in plasma. Furthermore,
      circulating levels of HA reflect the dynamic state between delivery to-and
      removal from-the bloodstream. To develop an accurate estimation of the fluid
      volume distribution and dynamics, the rate of lymph flow needs to be taken into
      account and hyaluronan could be used as a marker in estimating this flow. To
      examine the HA distribution and system fluid dynamics, a six-compartment model,
      which could reflect both the steady-state relationships and qualitative
      characteristics of the dynamics, was developed. This was then applied to estimate
      fluid shifts from the interstitial space via the lymphatic system to the plasma
      during different physiological stresses (orthostatic stress and the stress of
      ultrafiltration during dialysis). Sensitivity analysis shows that during
      ultrafiltration, lymph flow is a key parameter influencing the total HA level,
      thus suggesting that the model may find applications in addressing the problem of
      estimating lymph flow. Since the fluid balance between interstitium and plasma is
      maintained by lymph flow and microvasculature filtration, our novel method of
      flow estimation may provide an important tool for understanding fluid dynamics
      during perturbations of the cardiovascular system. Since the fluid balance
      between interstitium and plasma is maintained by lymph flow and microvasculature
      filtration, our novel method of flow estimation may provide an important tool for
      understanding fluid dynamics during perturbations of the cardiovascular system.

PMID- 21743126
TI  - Heart rate variability analysis using a ballistocardiogram during Valsalva
      manoeuvre and post exercise.
AB  - We introduced a novel non-constrained technique for estimating heart rate
      variability (HRV) using a ballistocardiogram (BCG). To assess whether the BCG
      signal can be used to analyse the cardiac autonomic modulation, HRV parameters
      derived from the BCG signal (ballistocardiographic HRV, B-HRV) were statistically
      compared with the HRV parameters from the ECG signal during rest and under two
      different experimental conditions that induce cardiac autonomic rhythm changes:
      the Valsalva manoeuvre and static exercise. Time domain, frequency domain and
      nonlinear analyses were individually performed on 15 healthy subjects to assess
      whether the BCG can be used to analyse the cardiac autonomic modulation under
      each condition. For all subjects, the proposed method had averages of relative
      errors of 5.01 +/- 4.72, 5.64 +/- 4.83 and 5.98 +/- 5.80% for resting, Valsalva
      and post-exercise sessions, respectively, and the correlation coefficients
      between the reference (ECG) and proposed (BCG) methods are 0.97, 0.98 and 0.98,
      for resting, Valsalva and post-exercise sessions, respectively. During cardiac
      autonomic changes, the B-HRV parameters changed in a pattern that is very similar
      to the variations in the HRV parameters based on Student's t-test results. In
      addition, some of the B-HRV parameters changed according to cardiac autonomic
      rhythms controlled by sympathetic and parasympathetic activities during the
      experiments. These findings indicate that BCG can provide an accurate and
      reliable means to evaluate autonomic system activation by HRV in its
      unconstrained way.

PMID- 21743128
TI  - Free energy considerations for nucleic acids with dangling ends near a surface: a
      coarse grained approach.
AB  - A coarse grained model for the thermodynamics of nucleic acid hybridization near
      surfaces has been extended and parameterized to consider the contribution of
      unpaired dangling ends. The parameters of the model differ when representing a
      double stranded DNA section or a single stranded DNA section. The thermodynamic
      effects of the possibility of different dangling end combinations were considered
      in the presence of different types of surfaces. Configurational sampling was
      achieved by the Metropolis Monte Carlo method. To gain a more complete picture of
      the free energy changes, an estimation of the conformational entropy was
      included. We find a strong thermodynamic effect for dangling mismatches due to
      sequence requirements when they are nearer the surface as opposed to being held
      away from the surface.

PMID- 21743129
TI  - Electrostatic contribution to DNA condensation--application of 'energy
      minimization' in a simple model in the strong Coulomb coupling regime.
AB  - The process of bending of straight DNA to a circular form in the presence of any
      of the mono-, di-, tri- or tetravalent counterions has been simulated in a strong
      Coulomb coupling environment, employing a previously developed energy
      minimization simulation technique. The inherent characteristics of the simulation
      technique allow the monitoring of the required electrostatic contribution to the
      bending. The curvature of the bending has been found to play a crucial role in
      facilitating the electrostatic attractive potential energy. The total
      electrostatic potential energy has been found to decrease with bending, which
      indicates that bending straight DNA to a circular form or to a toroidal form in
      the presence of neutralizing counterions is energetically favourable and is
      practically a spontaneous phenomenon.

PMID- 21743130
TI  - Disturbed neurotransmitter transporter expression in Alzheimer's disease brain.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory
      loss and behavioral and psychological symptoms of dementia. An imbalance of
      different neurotransmitters--glutamate, acetylcholine, dopamine, and serotonin-
      has been proposed as the neurobiological basis of behavioral symptoms in AD. The
      molecular changes associated with neurotransmission imbalance in AD are not
      clear. We hypothesized that altered reuptake of neurotransmitters by vesicular
      glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the
      vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter
      (SERT), or the dopamine reuptake transporter (DAT) are involved in the
      neurotransmission imbalance in AD. We tested this hypothesis by examining protein
      and mRNA levels of these transporters in postmortem prefrontal cortex from 10 AD
      patients and 10 matched non-AD controls. Compared with controls, protein and mRNA
      levels of VGLUTs, EAAT1-3, VAChT, and SERT were reduced significantly in AD.
      Expression of DAT and catechol O-methyltransferase was unchanged. Reduced VGLUTs
      and EAATs may contribute to an alteration in glutamatergic recycling, and reduced
      SERT could exacerbate depressive symptoms in AD. The reduced VAChT expression
      could contribute to the recognized cholinergic deficit in AD. Altered
      neurotransmitter transporters could contribute to the pathophysiology of AD and
      are potential targets for therapy.

PMID- 21743131
TI  - Deficits in spatial learning and memory is associated with hippocampal volume
      loss in aged apolipoprotein E4 mice.
AB  - Apolipoprotein E epsilon4 (ApoE4) has been implicated as a potential genetic risk
      factor for dementia. In this study, we investigate the effect of ApoE4 on
      learning and memory, changes in brain volume and neuroinflammatory responses in
      brain of ApoE4 transgenic mice. Four groups of male mice with ApoE4 and age
      matched wild type (WT) (6-, 12-, 18- and 24-month) were studied. Spatial learning
      and retaining of mice was examined in the Morris Water Maze (MWM). Changes in
      brain volume (including the whole brain, hippocampus, cortex, total ventricles,
      and caudate putamen) were assessed by using 7T small animal MRI.
      Neuroinflammatory responses were analyzed by measuring the levels of microglia
      (Iba-1), iNOS, TNFalpha, and IL-6 quantitatively. In the MWM, ApoE4 mice showed
      longer escape latency (p < 0.05) and swim distance (p < 0.05) at age 12 month and
      older, comparing with the WT mice. They also demonstrated poor memory retention
      in the probe test (p < 0.05). Brain atrophy was significant in ApoE4 mice than
      age-matched WT mice (18 months: 0.079 +/- 0.004 versus 0.086 +/- 0.003, p =
      0.018; and 24 months: 0.074 +/- 0.005 versus 0.084 +/- 0.006, p = 0.008). The
      expression of Iba-1, iNOS, and TNFalpha in hippocampus and cortex were
      significantly higher in ApoE4 mice than in WT mice at 12 months and older. These
      data suggest that ApoE4 plays an important role in learning and memory
      impairment. These deficits are associated with neuroinflammatory responses that
      may in turn lead to atrophy in hippocampus and cortex.

PMID- 21743132
TI  - Grape seed polyphenolic extract specifically decreases abeta*56 in the brains of
      Tg2576 mice.
AB  - Amyloid-beta (Abeta) oligomers, found in the brains of Alzheimer's disease (AD)
      patients and transgenic mouse models of AD, cause synaptotoxicity and memory
      impairment. Grape seed polyphenolic extract (GSPE) inhibits Abeta oligomerization
      in vitro and attenuates cognitive impairment and AD-related neuropathology in the
      brains of transgenic mice. In the current study, GSPE was administered to Tg2576
      mice for a period of five months. Treatment significantly decreased brain levels
      of Abeta*56, a 56-kDa Abeta oligomer previously shown to induce memory
      dysfunction in rodents, without changing the levels of transgenic amyloid-beta
      protein precursor, monomeric Abeta, or other Abeta oligomers. These results thus
      provide the first demonstration that a safe and affordable intervention can lower
      the levels of a memory-impairing Abeta oligomer in vivo and strongly suggest that
      GSPE should be further tested as a potential prevention and/or therapy for AD.

PMID- 21743133
TI  - Uncertain progress on the fuzzy boundaries of Alzheimer's disease: reading
      between the guidelines.

PMID- 21743137
TI  - Clinical challenges in the ataxias.
AB  - Ataxias are rare diseases and the etiologic heterogeneity make individual
      entities even rarer. There are still substantial numbers of patients who are
      still poorly understood. Available assessment techniques still point to large
      numbers of patients needed for clinical trials and the need for cooperative
      efforts, better assessment tools and novel trial designs. Better understanding of
      neural circuitry abnormalities may lead to more effective symptomatic therapy.
      Opportunities exist for targeting at risk individuals for effective therapies but
      how this can be done is not clear. Preventive strategies may become feasible in
      many ataxias.

PMID- 21743136
TI  - Neuroprotective action of lithium in disorders of the central nervous system.
AB  - Substantial in vitro and in vivo evidence of neurotrophic and neuroprotective
      effects of lithium suggests that it may also have considerable potential for the
      treatment of neurodegenerative conditions. Lithium's main mechanisms of action
      appear to stem from its ability to inhibit glycogen synthase kinase-3 activity
      and also to induce signaling mediated by brain-derived neurotrophic factor. This
      in turn alters a wide variety of downstream effectors, with the ultimate effect
      of enhancing pathways to cell survival. In addition, lithium contributes to
      calcium homeostasis. By inhibiting N-methyl-D-aspartate receptor-mediated calcium
      influx, for instance, it suppresses the calcium-dependent activation of pro
      apoptotic signaling pathways. By inhibiting the activity of phosphoinositol
      phosphatases, it decreases levels of inositol 1,4,5-trisphosphate, a process
      recently identified as a novel mechanism for inducing autophagy. These mechanisms
      allow therapeutic doses of lithium to protect neuronal cells from diverse insults
      that would otherwise lead to massive cell death. Lithium, moreover, has been
      shown to improve behavioral and cognitive deficits in animal models of
      neurodegenerative diseases, including stroke, amyotrophic lateral sclerosis,
      fragile X syndrome, and Huntington's, Alzheimer's, and Parkinson's diseases.
      Since lithium is already FDA-approved for the treatment of bipolar disorder, our
      conclusions support the notion that its clinical relevance can be expanded to
      include the treatment of several neurological and neurodegenerative-related
      diseases.

PMID- 21743138
TI  - Spinocerebellar ataxias in mainland China: an updated genetic analysis among a
      large cohort of familial and sporadic cases.
AB  - OBJECTIVE: To undertake an updated genetic spectrum analysis in patients with
      hereditary spinocerebellar ataxia (SCA) in mainland China. METHODS: SCA 1, 2, 3,
      6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) nucleotide
      repeat mutations were detected in 430 families with autosomal dominant SCA (ADCA)
      and 237 patients with sporadic ataxias by PCR and DNA sequencing. Subsequently,
      point and Indel (Insertion/deletion) mutation analyses of SCA5, SCA11, SCA13,
      SCA14, SCA15/16/29, SCA27, SCA31 and SCA35 were detected in 91 families with ADCA
      and 196 patients with sporadic ataxias excluded from SCA1, 2, 3, 6, 7, 8, 10, 12,
      17 and DRPLA genotypes via PCR and Denaturing High Performance Liquid
      Chromatography (PCR-DHPLC), Multiplex ligation-dependent probe amplification and
      DNA direct sequencing analysis. RESULTS: Among the 430 ADCA families, there were
      25 SCA1 (5.81%), 27 SCA2 (6.28%), 267 SCA3/MJD (62.09%), 8 SCA6 (1.86%), 8 SCA7
      (1.86%), 1 SCA12 (0.23%), 1 SCA17 (0.23%) and 2 SCA35 (0.47%), and the remaining
      91 families (21.16%) were genetically unidentified. Among the 237 sporadic SCA
      patients, there were 6 SCA1 (2.53%), 9 SCA2 (3.80%), 23 SCA3/MJD (9.70%) and 3
      SCA6 (1.27%), and the remaining 196 (82.7%) were genetically unidentified. No
      pathogenic point mutation causing SCA5, SCA11, SCA13, SCA14, SCA27 or SCA31
      subtypes was found. CONCLUSION: SCA3/MJD is substantially the most common subtype
      in patients with ADCA and sporadic forms in mainland China, followed by SCA2,
      SCA1, SCA6 and SCA7. While SCA12, SCA17 and SCA35 are seldom found, SCA5, SCA8,
      SCA10, SCA11, SCA13, SCA27, SCA31 and DRPLA are very rare. The high proportion of
      genetically unidentified cases further verify that SCAs are of highly genetic
      heterogeneity, suggesting that other disease-causing genes might be involved in
      the negative ADCA pedigrees, and other etiological factors may involve in those
      sporadic cases other than genetics.

PMID- 21743139
TI  - Mutation analysis of PINK1 gene in patients with early-onset Parkinsonism.
AB  - OBJECTIVE: To determine the frequency of mutations in PINK1 in Chinese Han people
      with sporadic early-onset Parkinsonism (EOP). METHODS: DNA sequencing was used to
      detect point mutations and small deletions/insertions, and quantitative real-time
      PCR was carried out to detect deletions/insertions and rearrangements in 149
      patients and 150 healthy controls. RESULTS: Four heterozygous mutations in PINK1
      were identified, including 3 missense mutations (c.832C>G, c. 938C>T, c.1 220G>A)
      and ex 3-8 del. A novel single nucleotide polymorphism (SNP) c.899+18G>A and 14
      reported SNPs were identified. Chi-square test showed that c.189C> T and c.960
      5G>A had significant difference in the genotype frequencies and allele
      frequencies between the patients and the controls (for c.189C>T genotype
      chi(2)=21.244,P<0.0001; T allele chi(2)=24.353,P<0.0001, and for c.960-5G>A
      genotype's chi(2)=6.524,P =0.038; A allele chi(2)=6.725,P=0.0095). CONCLUSION:
      About 3.35% Chinese Han patients with EOP carry mutations in PINK1. Two SNPs
      c.189C>T and c.960-5G>A may contribute to the risk of EOP in Chinese Han people.

PMID- 21743140
TI  - Related factors of ICARS and SARA scores on spinocerebellar ataxia type 3/Machado
      Joseph disease.
AB  - OBJECTIVE: To investigate the related factors of international cooperative ataxia
      rating scale (ICARS) and scale for the assessment and rating of ataxia scores
      (SARA) in patients with spinocerebellar ataxia type 3/Machado-Joseph disease.
      METHODS: A total of 126 SCA3/MJD patients were assessed by ICARS and SARA. The
      relation between ICARS or SARA scores and age of onset, disease duration and CAG
      repeat size was analyzed. RESULTS: Either the total ICARS or the total SARA score
      was positively related with the disease duration(r=0.586,P<0.05;r=0.643,P<0.05).
      Simple linear regression equations were: Y(1)(total ICARS score)=13.072+2.388
      X(2)(disease duration)(F=68.874,P<0.05); Y(2)(total SARA score)=4.403+ 0.961
      X(2)(disease duration)(F=87.254, P<0.05). Either age adjusted the total ICARS
      score or age adjusted the total SARA score was positively related with CAG repeat
      size(r=0.328, P<0.05; r=0.335, P<0.05). Both the ICARS subscores and the SARA
      subscores were positively related with the disease duration(r=0.257-0.589,
      P<0.05; r=0.432-0.623, P<0.05). Both age adjusted ICARS subscores and age
      adjusted SARA subscores were positively related with CAG repeat size(r=0.263
      0.403, P<0.05; r=0.189-0.366, P<0.05). Analysis of variance showed that the total
      ICARS score and the total SARA score increased with the disease stage.
      CONCLUSION: ICARS and SARA are both reliable and effective scales in assessing
      the severity of ataxia in patients with SCA3/MJD, and researchers can choose the
      most suitable scale according to specific requirement.

PMID- 21743141
TI  - Serum concentrations of NSE and S100B in spinocerebellar ataxia type 3/Machado
      Joseph disease.
AB  - OBJECTIVE: To determine the neuronal damage or loss and gliosis at the cellular
      level in spinocerebellar ataxia type 3/Machado-Joseph disease(SCA3/MJD), and
      evaluate the potential use of neuron-specific enolase (NSE) and protein S 100
      B(S100B) serum concentrations as biochemical markers. METHODS: Serum
      concentrations of NSE and S100B were measured in 102 SCA3/MJD patients and 100
      healthy subjects matched by sex and age. The correlations between both markers
      and age, age of onset, disease duration, CAG repeat size, scores of international
      cooperative ataxia rating scale(ICARS), and scale for the assessment and rating
      of ataxia(SARA) were analyzed. RESULTS: Compared with the healthy controls,
      patients with SCA3/MJD had higher NSE serum concentrations [(6.95 +/- 2.83)ng/mL
      vs (4.83 +/- 1.70) ng/mL, P<0.05] and higher S100B serum concentrations [(0.07 +/
      0.06) ng/mL vs (0.05 +/- 0.02) ng/mL, P<0.05]. In the SCA3/MJD patients group,
      NSE levels presented a positive correlation with age, disease duration, ICARS
      scores and SARA scores, whereas S100B levels did not correlate with age, age of
      onset, disease duration, ICARS scores and SARA scores. CAG repeat size did not
      correlate with the NSE levels and S100B levels in different age groups of
      SCA3/MJD patients. CONCLUSION: Serum NSE might be a useful marker to monitor
      disease progression and represent the degree of severity of a certain disease.
      Elevated S100B serum concentrations in patients compared to healthy controls may
      suggest an application of this protein as a peripheral marker of brain impairment
      in SCA3/MJD.

PMID- 21743142
TI  - Magnetic resonance spectroscopy of the cerebellum in patients with
      spinocerebellar ataxia type 3/Machado-Joseph disease.
AB  - OBJECTIVE: To evaluate the metabolite pattern and the severity in patients with
      spinocerebellar ataxia type 3/ Machado-Joseph disease (SCA3/MJD) by (1)H magnetic
      resonance spectroscopy ((1)H-MRS) on different cerebellar regions, including
      cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum.
      METHODS: Thirty-six SCA3/MJD patients, and 27 sex, age-matched healthy controls
      were scanned with (1)H-MRS for N-acetylaspartate (NAA), choline (Cho) and
      creatine (Cr). We made cerebellar vermis, cerebellar peduncles, cerebellar
      cortex, and dentatum as the region of interests (ROI), and finally got access to
      NAA/Cr, Cho/Cr, and NAA/Cho ratios. We also examined the CAG repeat numbers of
      MJD1 gene, scored the 36 patients by the scale for the assessment and rating of
      ataxia (SARA), analyzed the differences in ratios between SCA3/MJD patients and
      the control group, and explored whether relevance existed between these ratios
      and duration of the disease, age of onset, CAG repeat times, and SARA scores
      respectively. RESULTS: The ratio of NAA/Cr in SCA3/MJD patients showed a
      significant reduction in the cerebellar cortex, dentatum, cerebellar vermis and
      medipeduncle (P<0.01) compared with the controls. The ratio of NAA/Cho also
      showed significant reduction in the dentatum and cerebellar vermis (P<0.01). A
      number of correlations were found between the metabolite ratios of (1)H-MRS and
      duration of the disease, age of onset, expanded CAG and SARA score in SCA3/MJD
      patients. CONCLUSION: (1)H-MRS, which shows the neural metabolic changes in the
      cerebella of SCA3/MJD patients, provides useful information about the severity of
      SCA3/MJD.

PMID- 21743143
TI  - [Clinical, familial and hereditary analysis of myotonic dystrophy].
AB  - OBJECTIVE: To analyze the clinical, familial and hereditary features of myotonic
      dystrophy to improve the knowledge and provide molecule evidence for gene
      diagnosis and prenatal diagnosis of myotonic dystrophy or dystrophia myotonia
      (DM) families. METHODS: Clinical data of 2 DM families were collected based on
      the probands. The number of trinucleotide CTG repeat in the 3' untranslated
      region of myotonic dystrophy protein kinase (DMPK) gene on chromosome 19 was
      determined by DNA sequence and repeat fragment. RESULTS: Except for 1 subclinical
      patient, another 5 patients progressed slowly with the features of myotonic
      muscular weakness and atrophy. One patient had hatchet face, 1 had cataract and
      diabetes mellitus, and the other 3 were bald. Electromyologram showed 3 patients
      had myotonic discharge and myopathic abnormalities. The number of trinucleotide
      CTG repeat in the 3' untranslated region of DMPK gene of 5 patients exceeded 50.
      CONCLUSION: DM can be anticipated. Gene analysis can verify the disease and
      identify subclinical patients. It helps to prevent the DM births by hereditary
      consultation performing prenatal diagnosis.

PMID- 21743144
TI  - Transversal inducing differentiation of human amniotic epithelial cells into
      hepatocyte-like cells.
AB  - OBJECTIVE: To evaluate the in vitro differentiation of human amniotic epithelial
      cells (hAECs ) into hepatocyte-like cells. METHODS: Combined approach of
      dexamethasone, HGF, IGF and other cytokines were used to induce the
      differentiation of hAECs into hepatocyte-like cells. The induction lasted 2
      weeks. During the induction, the expression of albumin ALB, CYP1A1, CYP1A2, IGFR,
      c-met and key functional genes related to liver cells as well as transcription
      factors HNF3, HNF4 and C/EBPa were monitored by RT-PCR. Time dependent changes of
      the surface marker colony ALB, AFP and CK18 were analyzed by cell flow cytometry.
      RESULTS: After the 2 week induction, the expressions of liver hepatocyte-like
      cell functional genes such as albumin, CYP1A1, CYP1A2, c-met, and transcription
      factors such as HNF3, HNF4, C/EBPa and HNF1 were observed. Six days after the
      induction, hAECs mainly were stained AFP+, and the positive rate was (15.1 +/-
      2.1)%. While 10 days after the induction, part of the hAECs showed AFP+/ALB+ (6.5
      +/- 1.4)%; and on 14th day, hAECs only showed ALB+, and the rate was (13.9 +/-
      2.3)%. ALB+ cell increase indicated a gradual functional maturation from the
      hAECs to hepatocyte-like cells. Similaritly, the number of CK18+ cells in the
      whole population was also increased: On 10th day, the rate was (16.1 +/- 1.2)%;
      on 14th day, that was (21.3 +/- 4.6)%, which proved the above hypothesis of the
      trandifferentiation. By extending the induction time, the expression of
      functional genes increased gradually, and a maturing process of hAECs was
      detected by cell surface markers. CONCLUSION: The differentiation of hAECs
      induced in vitro has the characteristics of hepatocyte-like cells.

PMID- 21743145
TI  - Cognitive emotion regulation questionnaire in hypertensive patients.
AB  - OBJECTIVE: To examine the reliability,validity,and practicability of Cognitive
      Emotion Regulation Questionnaire (CERQ) in hypertensive patients in China.
      METHODS: Altogether 434 hypertensive patients and 462 healthy subjects were
      recruited. All the subjects were assessed with the CERQ-Chinese version (CERQ-C),
      Dysfunctional Attitude Scale (DAS), Mood and Anxiety Symptom Questionnaire-Short
      Form (MASQ-SF), and Center for Epidemiologic Studies Depression Scale (CES-D). We
      calculated the mean inter-item correlations for the total CERQ and for each of
      the subscales. Cronbach's alpha coefficient was used to analyze the inter
      correlation and reliability, and confirmatory factor analysis was used to examine
      the 9-factor model. RESULTS: 1) Hypertension group reported significantly higher
      score than that of healthy ones on rumination (12.19 +/- 2.51 vs. 11.51 +/- 2.60,
      P<0.001), catastrophizing(8.82 +/- 2.19 vs.8.11 +/- 2.70,P<0.001),and blaming
      others(10.76 +/- 2.11 vs. 9.88 +/- 2.48,P<0.001), and had significantly lower
      score than that of healthy ones on positive reappraisal(13.80 +/- 3.55 vs.14.71
      +/- 4.11,P<0.001).2)Reliability:In the hypertension group the Cronbach's alpha
      for the total CERQ was 0.80, and that for the 9 subscales ranged from 0.71 (self
      blame) to 0.90 (rumination). In the healthy group the Cronbach's alpha for the
      total CERQ was 0.79, and that for the 9 subscales ranged from 0.71 (positive
      reappraisal) to 0.90 (rumination). The mean inter-item correlation coefficient
      for the 9 subscales was 0.21-0.42(the hypertension group)/0.19-0.32 (the healthy
      group). In the hypertension group,the test-retest reliability of the total scale
      was 0.82, the test-retest reliability of the 9 subscales ranged from 0.73 to
      0.92. The confirmatory factor analysis showed that the 9 first-order factor data
      fitted both 2 samples well. CONCLUSION: CERQ meets the psychometric standard and
      it is reliable and valid for cognitive emotion regulation strategies, which may
      be regarded as an appropriate assessment tool.

PMID- 21743146
TI  - [Effect of bone morphogenetic protein-4 on the proliferation and differentiation
      of rat hepatic precursor cells].
AB  - OBJECTIVE: To determine the regulation effect of bone morphogenetic protein-4
      (BMP-4) on the proliferation and differentiation of rat hepatic precursor cells.
      METHODS: We used Noggin (200 ng/mL) as the function blocking control of BMP-4,
      and the hepatic precursor cells of WB-F344 were treated with recombinant BMP-4 at
      50 ng/mL at different time points. The proliferation of WB-F344 cells were tested
      by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The ultrastructural
      characters of differentiated WB-F344 cells regulated by BMP-4 were observed under
      a transmission electron microscope. RT-PCR was used to examine mRNA expression of
      specific molecular markers for different cellular phenotypes potentially
      differentiated from the WB-F344 cells. RESULTS: At different time points, the
      absorbance values in the BMP-4 treatment groups were higher than those in the
      control groups of Noggin and blank treatment (P<0.01). The WB-F344 cells treated
      with BMP-4 exhibited typical ultrastructural characters of well-differentiated
      epithelial cells. The hepatocyte mRNA markers were more significantly promoted in
      the differentiated WB-F344 cells in the BMP-4 treatment group than those in the
      other 2 control groups. CONCLUSION: BMP-4 can promote the proliferation and
      directional differentiation towards hepatocytes of rat hepatic precursor cells of
      WB-F344.

PMID- 21743147
TI  - [Effects of hepatic insulin gene therapy on enteric neuropathy in STZ-diabetic
      mice].
AB  - OBJECTIVE: To evaluate the effect of hepatic insulin gene therapy on diabetic
      enteric neuropathy. METHODS: Mice were randomly allocated into 3 groups: a normal
      control group, a diabetic group, and a diabetic gene therapy group. Diabetes were
      induced by penial vein injection of streptozocin (STZ). The gene therapy group
      received hepatic insulin gene therapy while the other 2 groups only received an
      empty virus expressing green fluorescent protein. Random blood glucose, body
      weight growth, gastric emptying, total bowel length, absolute and relative bowel
      transit, electric field stimulation of colon smooth muscle, colon nuclei staining
      and counting were measured. RESULTS: We successully established a mouse model of
      diabetic enteric neuropathy which manifests as: 8 weeks of continuous
      hyperglycemia,increased total bowel length, decreased relative bowel transit,
      impaired colon smooth muscle relaxation and loss of inhibitory neurons in colon.
      Through gene therapy, the above indexes were normalized or ameliorated,
      suggesting hepatic insulin gene therapy is capable of preventing diabetic enteric
      neuropathy. CONCLUSION: Hepatic insulin gene therapy can prevent STZ induced
      diabetic enteric neuropathy.

PMID- 21743148
TI  - [Inhibitory effect of GnRHII and GnRH Ia on the stromal cell proliferation from
      endometriosis patients].
AB  - OBJECTIVE: To investigate the inhibitory effect of gonadotropin-releasing hormone
      II(GnRHII) and gonadotropin-releasing hormone I agonist (GnRH Ia) on the
      proliferation of endometrial stromal cells in vitro from endometriosis patients.
      METHODS: Different concentrations of GnRHII or GnRH Ia were added into the
      cultured endometrial stromal cells in vitro to detect the cell proliferation
      inhibition by MTT test. RESULTS: The inhibitory rate of GnRHII or GnRH Ia on
      eutopic and ectopic endometrial stromal cells in vitro was both dose- and time
      dependent (P<0.05). Effect of GnRHII or GnRH Ia on the inhibitory rate of ectopic
      endometrial stromal cells was significantly higher than that of eutopic (P<0.05).
      GnRH II had a higher inhibitory rate on the endometrial stromal cells in vitro
      than did GnRH Ia (P<0.05). CONCLUSION: GnRHII has more antiproliferative effect
      on endometrial stromal cells than GnRH Ia in vitro, especially on ectopic
      endometrial stromal cells, suggesting that GnRHII may be more effective than GnRH
      Ia on endometriosis.

PMID- 21743149
TI  - [Regulation of invasion behavior of ERK-mediated trophoblast by focal adhesion
      kinase].
AB  - OBJECTIVE: To investigate the role of focal adhesion kinase (FAK) in
      extracellular signal-regulated kinase (ERK) signaling pathway mediated invadsion
      of trophoblasts. METHODS: We established a human extravillous cytotrophoblasts in
      vitro invasion model. Different concentrations of herbimycin A(FAK inhibitor)and
      PD98059 (ERK inhibitor) were given to observe the influence on the growth of
      trophoblast cells, FAK, ERK phosphorylation, and trophoblast invasion abilities.
      RESULTS: The expression of phosphorylated FAK in the extravillous
      cytotrophoblasts (EVCT) was inhibited by herbimycin A in a concentration
      dependent manner and expression of phosphorylated ERK1/2 was also partially
      reduced. PD98059 had no effect on the expression of phosphorylated FAK.
      Herbimycin A and PD98059 suppressed the in vitro invasion of EVCT to various
      degrees. CONCLUSION: ERK signaling pathway may be the common pathway for many
      invasive signals,and play a key role in the regulation of trophoblast invasion.

PMID- 21743150
TI  - [Expression of Merlin protein in non-small cell lung carcinoma and the clinical
      significance].
AB  - OBJECTIVE: To determine the expression and clinical significance of Merlin
      protein in non-small cell lung cancer (NSCLC). METHODS: The expression of Merlin
      protein in 45 cases of NSCLC and adjacent tissue of NSCLC and normal lung tissue
      was checked by immunohistochemistry. The relation between the expression of
      Merlin protein and the multiple factors of pathological type, gender, P-TNM
      stage, differentiation and lymph node metastasis was analyzed. RESULTS: The
      expression rates of Merlin protein in NSCLC and normal lung tissue sections were
      73.33% and 15.56%, respectively (P<0.05). The expression of Merlin protein was
      not associated with the pathological type, gender, P-TNM stage, differentiation
      and lymph node metastasis (P>0.05). CONCLUSION: Merlin protein might contribute
      to the initiation of metastasis of NSCLC.

PMID- 21743151
TI  - [Meta-analysis of proximal gastrectomy and total gastrectomy for cancer of cardia
      and fundus].
AB  - OBJECTIVE: To assess the value of proximal gastrectomy (PG) and total gastrectomy
      (TG) for the treatment of cancer of cardia and fundus. METHODS: Publications on
      comparision between PG and TG in the treatment of cancer of cardia and fundus
      were collected, the data from the publications were matched with the PG group and
      the TG group respectively according to its corresponding surgical resection, and
      the data on postoperative complications, motality and 5-year survival rate were
      meta-analyzed by fixed effect model and random effect model. RESULTS: Thirteen
      reseaches on 2 219 patients were included in this study, 2 of which were randomly
      controlled studies. There were no significant differences in the postoperative
      complications (OR=1.00, 95%CI: 0.44-2.28,P>0.05) and mortality (OR=1.25, 95%CI:
      0.62-2.48,P>0.05) between the PG group and the TG group, while there was
      significant difference in the 5-year survival rate (HR=0.87, 95%CI: 0.76
      0.99,P=0.04). The 5-year survival rate in the TG group was higher than that in
      the PG group. CONCLUSION: Total gastrectomy for the treatment of cancer of cardia
      and fundus has better long-term therapetic effect.

PMID- 21743152
TI  - [Evaluation of minimally invasive peratrial device closure of secundum atrial
      septal defects in children].
AB  - OBJECTIVE: To introduce peratrial device closure of secundum atrial septal
      defects (ASD) under the guidance of transesophageal echocardiography (TEE)
      without cardiopulmonary bypass (CPB) in children, and to summarize the clinical
      experiences. METHODS: A total of 115 children with secundum ASD (the occlusion
      group) underwent peratrial device closure of atrial septal defects through a
      small sternotomy under TEE guidance without cardiopulmonary bypass. Children were
      followed up closely for 1-13 months. Another 59 children (the bypass group) had
      closed atrial septal defects under cardiopulmonary bypass during the same period.
      The differences in the operation duration, convalescence and complication between
      the 2 groups were compared. RESULTS: Except 1 patient was operated under the CPB,
      the rest 114 patients in the occlusion group were successfully closed by the
      occluders. The duration of the operation, mechanical ventilation, intensive care
      and hospitalization, and the rate of blood-transfusion in the occlusion group
      were significantly lower than those in the bypass group (P<0.01), with no
      difference in complications in the 2 groups (P>0.05). CONCLUSION: Minimally
      invasive peratrial device closure of ASD without CPB is a relatively simple, safe
      and effective operation under the guidance of TEE for children. The short and mid
      term clinical outcomes are promising. Long-term follow-up is indispensable.

PMID- 21743153
TI  - [Clinical characteristics of osteopetrosis in 4 children].
AB  - Four boys (2 months to 8 years old) were diagnosed with autosomal recessive form
      of osteopetrosis. Symptoms manifested in the first few months of life in 3
      patients, and there was family history in 1. Primary symptoms included anemia,
      thrombocytopenia, hepatosplenomegaly, failure to thrive, recurrent infectious
      history and macrocephaly. The typical radiological images on plain radiogram were
      diffuse sclerosis, bone modelling defects at the metaphyses of long bones, "bone
      in-bone" appearance, and "sandwich" vertebrae. Bone marrow biopsy showed markedly
      reduced platelets. Osteopetrosis refers to a group of rare, heritable disorders
      of the skeleton characterized by increased bone density on radiographs. Diffuse
      sclerosis leads to crowding of the bone marrow, resulting in anemia and
      extramedullary hemopoiesis. Hematopoietic stem cell transplantation is employed
      for the most severe forms associated with bone marrow failure and offers the best
      chance of longer-term survival.

PMID- 21743154
TI  - Management of minor and major endovascular intraprocedural aneurysm perforations.

PMID- 21743155
TI  - Spatial normalization of BOLD fMRI data in cases of qualitative gross
      neuroanatomical changes resulting from pathology.

PMID- 21743156
TI  - Rosai-Dorfman disease and neurological manifestations.

PMID- 21743157
TI  - Diffusion-weighted imaging signal hyperintensity in subacute combined
      degeneration of the spinal cord.

PMID- 21743158
TI  - Differentiation between the motor and sensory fascicles of the peripheral nerves
      from adult rats using annexin V-CdTe-conjugated polymer.
AB  - BACKGROUND: Until now, no method has been available to rapidly differentiate
      between the motor and sensory nerve fascicles introperatively. AIM: To establish
      a method to rapidly differentiate between the sensory and motor fascicles in the
      peripheral nerves. MATERIAL AND METHODS: Annexin V-CdTe-conjugated polymer was
      used to stain the sciatic and sural nerve fascicles of adult male Wistar rats for
      10, 15, 20, and 30 min. RESULTS: Under a light microscope, the sural nerves and
      the sensory fascicles of the sciatic were visualized as bright red fluorescence
      with Annexin V-CdTe-conjugated polymer staining. In contrast, no fluorescence on
      the motor fascicles of the sciatic nerve could be visualized. Fluorescence
      intensity was not strong enough to show the nerve fascicles with 10 min of
      staining; however, the intensity was clearly visible after 15 min of staining. No
      significant difference in the intensity of staining was observed among samples
      stained for 15, 20, and 30 min. CONCLUSIONS: Our study shows that Annexin V-CdTe
      conjugated polymer can differentiate the motor and sensory nerve fascicles of the
      peripheral nerve rapidly and precisely in vitro. This technique represents a new
      method for the identification of peripheral nerve fascicles.

PMID- 21743159
TI  - Non-normalized individual analysis of statistical parametric mapping for clinical
      fMRI.
AB  - BACKGROUND: Pre-operative evaluation to localize function within the cerebral
      cortices is essential before brain surgery. Blood oxygenation level-dependent
      functional magnetic resonance imaging (fMRI) has been used for this purpose.
      AIMS: To obtain clearer and more understandable functional images. PATIENTS AND
      METHODS: Ten patients with brain tumors underwent fMRI including hand-gripping
      and word generation tasks. The statistical parametric mapping (SPM) approach was
      used for subsequent analysis to localize the motor or language functions. SPM
      includes image pre-processing, statistical computation, and significance testing.
      In order to demonstrate a spatial relationship between the lesions and a
      functioning area in the individual structural MR images, normalization to the
      Montreal Neurological Institute coordinates was intentionally not performed.
      RESULTS: In seven cases out of 10, the patient's motor area was clearly
      visualized. Language areas were also demonstrated in seven cases. CONCLUSIONS: We
      conclude that application of SPM (version 8) analysis to non-normalized
      individual data for the purpose of performing pre-operative fMRI is a useful
      method for investigation of functional localization.

PMID- 21743160
TI  - Clinical spectrum of neurosyphilis in North East India.
AB  - BACKGROUND: Symptomatic neurosyphilis (NS) can have varied syndromic
      presentations: Meningitis, meningovascular and parenchymatous involvement. AIMS:
      To evaluate the different types of clinical syndrome of NS in a tertiary care
      hospital. MATERIAL AND METHODS: This was a study of clinical profile of 16
      patients with NS, seen in between August 2008 and December 2010. RESULTS: There
      were 13 male and 3 female patients in the age group of 23-48 years. The clinical
      syndromes included: Neuropsychiatric syndromes (10), myelopathy (5), and
      posterior circulation stroke (1). Neuropsychiatric symptoms were dementia,
      behavioral abnormalities, chronic psychosis, and myelopathy syndromes included
      acute transverse myelitis (ATM), chronic myelopathy, and syphilitic amyotrophy.
      Thirteen patients had positive venereal disease research laboratory test (VDRL)
      and/or high Treponema pallidum hemagglutination titer in blood. Cerebrospinal
      fluid was positive for VDRL in 14 patients, raised protein was seen in 13
      patients and lymphocytic pleocytosis was seen in 10 patients. Human
      immunodeficiency virus serology was negative in all the patients. Fourteen
      patients fulfilled the criteria of definitive NS and two of presumptive NS. All
      the patients except one received injection Procaine penicillin for 14 days. The
      patient with myelitis received a course of steroid, and one patient with
      associated hypothyroidism received thyroid supplement in addition to penicillin.
      On follow-up, dementia of short duration and ischemic stroke improved
      significantly and clinical status remained the same for ATM; others with mild
      symptoms improved with residual deficit. CONCLUSION: Syphilis can affect any part
      of the neuraxis. A high index of clinical suspicion is required to diagnose NS
      and institute the treatment early, particularly in patients with promiscuous
      sexual behavior.

PMID- 21743161
TI  - Early outcome after intravenous thrombolysis in patients with acute ischemic
      stroke.
AB  - BACKGROUND: Patients with acute ischemic stroke who had early neurological
      improvement had better functional outcome. The purpose of this study was to
      determine factors associated with early clinical improvement and early worsening
      in patients with acute ischemic stroke treated with intravenous thrombolysis.
      PATIENTS AND METHODS: Patients treated with intravenous recombinant tissue
      plasminogen activator (rtPA) between August 2008 and November 2010 were the
      subjects of this study. Early improvement was defined by marked, clinical
      improvement or complete recovery at 24 h (National Institutes of Health Stroke
      Scale (NIHSS) 0-4 at 24 h). Early worsening was defined by an increase in NIHSS
      >=1 from baseline. The baseline characteristics were compared between patients
      with and without outcome of interest. RESULTS: Of the 203 patients studied, 19
      (9.4%) patients had complete recovery and 68 (33.5%) patients had marked clinical
      improvement (NIHSS 1-4) at 24 h. Most patients with early clinical improvement
      (86%) had favorable outcome at three months. Of the 22 (10.8%) patients who had
      early clinical worsening, only three (14%) patients achieved favorable outcome at
      three months and six (29%) patients died. Multivariate analysis revealed that
      older age (>=70 years old) (odd ratio (OR) 0.498, P = 0.049), severe stroke
      (NIHSS >=15) (OR 0.154, P < 0.0001) and having intracerebral hemorrhage (ICH) (OR
      0.364, P = 0.032) were inversely associated with early improvement. History of
      transient ischemic attack (TIA) (OR 7.724, P = 0.043) and ICH (OR 4.477, P =
      0.008) were related to early worsening. CONCLUSIONS: The presence of early
      clinical improvement or worsening within 24 h after treatment with rtPA had major
      impact on the outcome at three months.

PMID- 21743162
TI  - A novel model of optic nerve injury established by microsurgery using the
      pterional approach in cats.
AB  - BACKGROUND: Experimental studies have yielded a wealth of information related to
      the pathological mechanism of optic nerve injury. However, there is no suitable
      animal model to study intracranial optic nerve injury. AIM: To establish an
      experimental model of acute optic nerve injury. MATERIAL AND METHODS: We
      established an animal model of acute intracranial optic nerve injury using the
      classic pterional approach in cats and investigated electrophysiological and
      ultrastructural changes. We applied immunohistochemical staining to examine the
      expression of glial fibrillary acid protein, neurofilament protein, myelin basic
      protein pre- and post-injury. RESULTS: We successfully established an animal
      model of acute intracranial optic nerve injury. CONCLUSION: The pathological
      processes of acute optic nerve injury may involve the following series of steps.
      Direct mechanical injury of the optic nerve leads to the death of
      oligodendrocytes in the optic nerve, which consequently results in optic nerve
      demyelination. Following optic nerve injury, the astrocytes in the injured area
      die and produce excitatory amino acids, which have an adverse effect on neurons,
      resulting in the proliferation and activation of astrocytes. The astrocytes can
      absorb the glutamic acid and transform it into atoxic glutamine. The glutamic
      acid can then injure retinal ganglion cells, resulting in the reduction of
      neurofilament proteins in the axons. We believe that the application of the
      pterional approach to establish optic nerve injury animal models has both a
      clinical and theoretical basis.

PMID- 21743163
TI  - Use of spinous processes to determine the laterally angulated trajectory for
      placement of lateral mass screws: an image analysis.
AB  - BACKGROUND: Lateral mass screw placement techniques have been broadly described
      in the literature. Differences in these techniques are related to entry points,
      lateral angulations and the cephalocaudal axis. AIM: We evaluated 20 patients who
      underwent lateral mass screw placement between 2007 and 2009. Computed tomography
      (CT) scans of the cervical vertebrae were analyzed for each patient. MATERIAL AND
      METHODS: We measured the maximal transition from the midpoint of the lateral mass
      to a proposed intersection point by a line connecting the corresponding spinous
      process and outermost rim of the transverse foramen at each level. This
      determined an optimal entry point during the tip of screw tilted on the same
      level of spinous process. RESULTS: The results revealed that a screw entry point
      less than 3 mm medial to the midpoint of the lateral mass could safely avoid
      violation of the vertebral artery. CONCLUSIONS: The current study uses imaging
      analysis to demonstrate that spinous processes are an intraoperative landmark to
      aid surgeons in determining safe lateral mass screw trajectories. The limited
      scale case results support our prediction from the image analysis. Depending on
      intraoperative landmarks, lateral mass screws could be safely and comfortably
      placed with good clinical outcomes.

PMID- 21743164
TI  - Intraprocedural cerebral aneurysm rupture during endovascular coiling.
AB  - BACKGROUND: Intraprocedural aneurysm rupture is considered to be one of the most
      formidable complications of the endovascular treatment of cerebral aneurysms and
      is associated with high mortality. OBJECTIVE: To report the clinical outcomes of
      cerebral aneurysms that ruptured during endovascular coiling. PATIENTS AND
      METHODS: Over a period of six years, 559 endovascular embolizations were
      performed in 467 patients, with 507 cerebral aneurysms. Intraprocedural aneurysm
      rupture occurred in 14 cases (mean aneurysm size, 3.8 mm). Follow-up angiograms,
      at a minimum of three months post embolization, were available in 11 living
      patients. Acute and follow-up results were reviewed. RESULTS: The difference in
      the rates of aneurysm perforation during endovascular coiling between ruptured
      and unruptured aneurysms was significant (P < 0.05). There were three (21.4%)
      deaths related to this complication and three (21.4%) patients developed new
      deficits (modified Rankin Scale scores 1 to 2). Acute results of embolization
      were: complete occlusion in eight (57.1%), neck remnant in two (14.3%), and
      incomplete occlusion in four (28.6%) patients. Long-term follow-up results in 11
      living patients were: major recanalization in one (9.1%), minor recanalization in
      one (9.1%), and stable occlusion in nine (81.8%). CONCLUSION: Intraprocedural
      aneurysm rupture frequently occurs in small aneurysms and appears to be
      associated with relatively high rates of mortality.

PMID- 21743165
TI  - Mechanical recanalization therapies for acute stroke: advances and uncertainties.

PMID- 21743166
TI  - Recent concepts in the management of extracranial carotid stenosis: carotid
      endarterectomy versus carotid artery stenting.
AB  - Carotid stenosis is seen in 10% of patients with ischemic stroke, and carotid
      endarterectomy (CEA) and carotid artery stenting (CAS) are the two invasive
      treatments options available. Pooled analysis of the three largest randomized
      trials of CEA involving more than 3000 symptomatic patients estimated 30-day
      stroke and death rate at 7.1% after CEA. Some subgroups among the symptomatic
      patients appeared to have more benefit from CEA. These include patients aged 75
      years or more, patients with ulcerated plaques, and patients with recent
      transient ischemic attacks within 2 weeks of randomization. Selection of
      asymptomatic patients for carotid revascularization should be guided by an
      assessment of comorbid conditions, life expectancy, and other individual factors,
      and should include a thorough discussion of the risks and benefits of the
      procedure with an understanding of patient preferences. The recent trials
      comparing CEA with CAS has not established its superiority over CEA. The carotid
      revascularization endarterectomy versus stenting (CREST) study showed that CAS is
      still associated with a higher periprocedural risk of stroke or death than CEA.
      In patients over 70 years of age, CEA is clearly superior to CAS. The increased
      risk of nonfatal myocardial infarction in the CREST group subjected to CEA
      clearly suggests that patients being considered for CEA or CAS require a careful
      preliminary cardiac evaluation. CAS can be justified for patients whose medical
      comorbidities or cervical anatomy make them questionable candidates for CEA. The
      benefit of revascularization by either method versus modern aggressive medical
      therapy has not been established for patients with asymptomatic carotid stenosis.

PMID- 21743167
TI  - Current status of stenting in intracranial atherosclerotic disease: the story
      thus far and the way ahead.
AB  - Despite medical management, symptomatic intracranial atherosclerotic disease has
      a high risk of stroke and death. This unacceptably high rate has provided the
      impetus for development and continuous advancements in the field of endovascular
      revascularization. From early attempts at angioplasty alone to state-of-the art
      stents including self-expanding and drug-eluting stents specially designed for
      the cerebral vessels, developments in this field has come a long way. As we stand
      today, however, there are still mixed views on the use of these endovascular
      techniques vs aggressive medical management. In this article, we review the
      mechanisms of stroke in patients with intracranial atherosclerotic disease and
      review the current status of stenting in this condition. A brief discussion of
      the important clinical and procedural considerations is also provided along with
      a mention of the ongoing trials likely to provide valuable information on the
      future of stenting.

PMID- 21743168
TI  - Carotid endarterectomy: results and long-term follow-up of a single institution.
AB  - OBJECTIVES: To document our experiences, technical procedure and outcomes of
      carotid endarterectomy (CEA) in patients with symptomatic carotid stenosis.
      MATERIAL AND METHODS: A total of 49 consecutive patients underwent 53 CEAs (three
      bilateral, one redo) for severe carotid artery stenosis. There were 39 males and
      10 females, with mean age of 63 years. All patients underwent neck Doppler,
      computed tomography/magnetic resonance angiography/digital substraction
      angiography and a detailed cardiological evaluation. Antiplatelet drugs were
      continued perioperatively. Surgery was performed under general anesthesia with
      propofol cerebral protection, mild hypothermia and continuous
      electroencephalogram monitoring. The procedure was done under microscope and
      closure was done using 6-0 prolene. Clinical and radiological follow-up was done.
      RESULTS: Our mean follow-up was 4.69 years. All patients underwent primary
      suturing except one redo CEA done with venous patch graft. Three patients
      required intraoperative shunting. One patient died secondary to myocardial
      infarction peroperatively prior to carotid manipulation. One patient had stroke
      within 6 h, secondary to operative site intraluminal thrombus and was re
      explored. Two patients had transient postoperative hemiparesis and aphasia while
      two patients had altered sensorium, all self-limiting, with normal imaging. One
      patient developed temporary twelfth-nerve paresis. One patient had persistent
      transient ischemic attack on the follow-up. Thus, the perioperative mortality
      rate was 1.89% and stroke rate was 1.89%. CONCLUSIONS: CEA for severe carotid
      stenosis is a safe procedure with good protection from ischemic events. Detailed
      preoperative cardiac evaluation and appropriate patient selection is essential.

PMID- 21743169
TI  - Percutaneous transluminal angioplasty and stenting of the vertebral artery ostium
      with balloon-mounted bare coronary stents.
AB  - BACKGROUND: Vertebral artery ostial stenosis (VAOS) is one of the most frequent
      causes of posterior circulation stroke. Percutaneous angioplasty and stenting
      (PTAS) is one of the treatment modalities. PATIENTS AND METHODS: This is a
      longitudinal observational study from September 2006 to February 2009, conducted
      at hospitals affiliated with the Shiraz University of Medical Sciences, Shiraz,
      southern Iran. The patient cohort included patients with posterior circulation
      stroke or transient ischemic attack (TIA) and more than 70% VAOS, and patients
      with asymptomatic VAOS of more than 70% and aplasia or total occlusion of the
      contralateral VA or subclavian artery. All the patients underwent PTAS with
      balloon-mounted bare coronary stents. Technical success, procedural
      complications, composite outcomes of death, stroke or TIA in the vertebrobasilar
      territory during the first 30 days, stroke or TIA in the vertebrobasilar
      territory, and restenosis during follow-up, were assessed. RESULTS: During the
      study period, 81 patients (mean age 68 + 8.9 years, 63 (78%) males, 71
      symptomatic and 18 asymptomatic) underwent the procedure. Technical success was
      achieved in 88 (99%) patients. Procedure-related complications, other than
      puncture site complications, were seen in two patients (2.2%). The composite
      outcome of death, stroke or TIA in the vertebrobasilar territory during the first
      30 days was 1%. None of the patients had clinical recurrence or restenosis during
      the follow-up (mean follow-up 14 months). CONCLUSION: Percutaneous transluminal
      angioplasty and stenting of the proximal VA was feasible and safe. The risk of
      restenosis should be analyzed in long-term studies with angiographic follow-up.

PMID- 21743170
TI  - Endovascular treatment for acute ischemic stroke using solitaire stent: temporary
      endovascular bypass, a novel technique.
AB  - Early restoration of flow to perfuse salvageable brain tissue has been shown to
      significantly reduce the morbidity and mortality of ischemic stroke. Several
      mechanical devices have shown promising results in patients with large vessel
      occlusive stroke. Solitaire revascularization device (ev3, Inc., Irvine,
      California) is a recoverable self-expanding thrombectomy device that can also be
      used as a temporary endovascular bypass. We report a patient in whom solitaire
      aneurysm bridging stent was used as a temporary bypass procedure to recanalize
      carotid T occlusion patient with good functional outcome.

PMID- 21743171
TI  - Five-year follow-up of stenting for a symptomatic posterior cerebral artery
      stenosis.
AB  - Angioplasty and stenting in symptomatic intracranial stenosis is technically
      possible and may reduce the risk of stroke in patients with symptomatic arterial
      stenosis. We report a patient with P1 segment stenosis of posterior cerebral
      artery treated successfully with angioplasty and stenting with a favorable
      outcome. He had 5 years of clinical and imaging follow-up and no in-stent
      stenosis or new ischemic event was observed.

PMID- 21743172
TI  - The functional SNP rs4376531 in the ARHGEF gene is a risk factor for the
      atherothrombotic stroke in Han Chinese.
AB  - The gene encoding RhoA guanine nucleotide exchange factor 10(ARHGEF10) has been
      reported to be a risk factor for atherothrombotic stroke (AS) in Japanese. The
      single-nucleotide polymorphism (SNP) rs4376531 in intron 16 on ARHGEF10 is
      associated with AS and may play a role in the disease pathology. In order to
      explore the nature of this association in greater detail and in a new ethnic
      group, we carried out a case-control study to determine whether the rs4376531
      polymorphism in ARHGEF10 is a risk factor of AS in Han Chinese people. This study
      was carried out to assay the frequency of genotypes and alleles of SNP rs4376531
      in ARHGEF10 in patients with ischemic stroke and healthy controls using the
      polymerase chain reaction and the restriction fragment length polymorphism (PCR
      RFLP) technique. A total of 383 individuals with AS in West China Hospital and
      214 unrelated healthy controls were recruited. The frequencies of the G allele
      and GG genotype of the rs4376531 polymorphism were higher in the patients with AS
      than in control individuals: frequency of G, 91.0% vs 83.4%, P<0.001; GG, 82.2%
      vs 67.8%, P<0.001. After adjusting for sex, age, and multiple cardiovascular risk
      factors, the homozygous GG genotype for this variant was associated with a higher
      risk of AS, with an adjusted odds ratio of 4.99 (95% CI, 2.55-7.81, P< 0.001).
      Our findings suggest that the rs4376531 polymorphism in the ARHGEF10 gene is a
      risk factor for AS in the Han Chinese population.

PMID- 21743173
TI  - Primary melanocytic tumors of the central nervous system: a neuroradiological and
      clinicopathological study of five cases and brief review of literature.
AB  - Primary melanocytic tumors of the central nervous system (CNS) are uncommon
      lesions. These lesions arise from the melanocytes located within leptomeninges
      and include diffuse melanocytosis and meningeal melanomatosis (seen in
      neurocutaneous melanosis), melanocytoma, and malignant melanoma. To study, the
      clinical course, neuroradiological features, morphology and immunohistochemistry
      of primary melanocytic tumor of CNS. Demographic, clinical and surgico-pathologic
      findings of five patients with melanocytic tumors seen between 1996 and 2003 were
      studied. In this study, five cases of primary melanocytic tumors have been
      reported: four cases of malignant melanoma and one case of melanocytoma. Three of
      the 5 cases were intracranial and 2 were spinal. The mean age in the present
      study was 26 years. Presenting features varied according to the location. Primary
      melanocytic tumor of CNS are rare. Whenever possible, complete surgical excision
      is the best treatment.

PMID- 21743174
TI  - Endovascular treatment for dural arteriovenous fistulas at the jugular foramen.
AB  - We report the technique and results of the endovascular treatment of jugular
      foramen dural arteriovenous fistulas (DAVFs) in 4 (3 men and 1 women, mean age
      50.75 years) symptomatic patients. The jugular foramen DAVFs accounted for 5.9%
      of intracranial DAVFs. Three patients presented with pulsatile tinnitus and 1
      patient presented with intracranial hemorrhage. Angiography demonstrated an AV
      fistula at the jugular foramen, mostly arising from the middle meningeal,
      ascending pharyngeal and vertebral arteries with direct drainage to the internal
      jugular vein. All patients underwent transarterial embolization using Onyx-18.
      Complete shunt obliteration was achieved in 3 patients; and shunt reduction, in 1
      patient, who was cured with additional surgery. Our study suggests that in
      jugular foramen DAVF transarterial embolization with Onyx should be considered
      when access is available.

PMID- 21743175
TI  - Surgical treatment and results in growing skull fracture.
AB  - Growing skull fracture is a rare complication of skull fracture and remains
      almost undetected in the first few years of life. Here, we report a series of 11
      patients with growing skull fracture treated at our institute over a period of
      five years and discuss their clinical features, radiological findings, and
      principles of management. Of the 11 patients, six were females and five males,
      with the age ranging between 9 months and 12 years (mean, 3 years). Progressive
      scalp swelling was the most common presenting feature. Other clinical features
      included generalised tonic clonic seizures, eyelid swelling, and proptosis.
      Computed tomography scan of the head defined the growing skull fracture in all 11
      patients and detected the underlying parenchymal injury. Postoperatively, all
      patients had a complete resolution of the scalp swelling. Two patients had
      postoperative seizures and one had cerebrospinal fluid leak. Early recognition
      and surgical repair is essential to prevent the development of neurological
      complications and cranial asymmetry.

PMID- 21743176
TI  - Hyperintense signal on spinal cord diffusion-weighted imaging in a patient with
      subacute combined degeneration.
AB  - Symmetrical hyperintense signals in lateral columns and posterior columns in T2
      weighted images is a characteristic finding in subacute combined degeneration
      (SCD) secondary to vitamin B12 deficiency. Manifestation of SCD on diffusion
      weighted imaging (DWI) has not been well characterised till date. We reported a
      case of SCD with spinal cord hyperintense signals in DWI sequence. We suggest
      that spinal cord DWI may be a useful magnetic resonance sequence for the
      diagnosis of SCD.

PMID- 21743177
TI  - Aphemia as a presenting symptom in acute stroke.
AB  - Aphemia is an apraxia of speech characterized by complete articulatory failure in
      the presence of preserved writing, comprehension and oropharyngeal function and
      can be the presenting manifestation of acute stroke. The responsible lesion is
      commonly in the left inferior frontal gyrus or the left motor cortex near the
      face M1 area. Three patients who developed aphemia due to acute ischemic stroke
      are described here. All had apraxia of speech due to acute infarct in the left
      motor cortex near face M1 area. Understanding the underlying speech disorder is
      crucial in planning the appropriate rehabilitation strategy.

PMID- 21743178
TI  - Recurrent pyogenic meningitis in a 17-year-old: a delayed presentation of X
      linked agammaglobulinemia with growth hormone deficiency.
AB  - We report an adolescent male with X-linked agammaglobulinemia (XLA) and recurrent
      episodes of pyogenic meningitis. The workup for proportionate short stature
      revealed isolated growth hormone deficiency. This patient highlights the delayed
      presentation of the XLA variant and the need to consider primary immunodeficiency
      in patients with recurrent serious infections, irrespective of age.

PMID- 21743179
TI  - Rosai-Dorfman disease presenting as cervical extradural lesion: a case report
      with review of literature.
AB  - Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease is a
      rare, but well documented entity. We report a lady who presented with progressive
      quadriparesis, with cervical extradural lesion on magnetic resonance imaging. She
      underwent decompression of the lesion and histological diagnosis of the lesion
      was Rosai-Dorfman disease. On one-year follow-up, she had complete improvement of
      the deficits with no further progression of the lesion. The presentation of this
      disease as an isolated spinal extradural mass lesion is quite rare, with only six
      cases reported in literature.

PMID- 21743180
TI  - Isolated intracranial Rosai Dorfman disease.
AB  - Rosai Dorfman disease (RDD), also known as sinus histiocytosis with massive
      lymphadenopathy, is a benign histiocytic proliferative disorder mainly affecting
      the lymph nodes. Although several cases of extra-nodal involvement have been
      reported previously, central nervous system involvement, particularly in the
      absence of nodal disease is extremely rare. We report a case of isolated
      intracranial RDD occurring in a relatively elder patient, which was shown by
      histological examination to have a dura-based involvement.

PMID- 21743181
TI  - Cervical intradural disc herniation and cerebrospinal fluid leak.
AB  - Cervical intradural disc herniation (IDH) is a rare condition and only 25 cases
      of cervical have been reported. We report a 45-year-old male who presented with
      sudden onset right lower limb weakness after lifting heavy weight. Magnetic
      resonance imaging of the cervical spine showed C5/6 disc prolapse with intradural
      extension. The patient underwent C5/6 discectomy through anterior cervical
      approach. Postoperatively, the patient improved in stiffness but developed
      cerebrospinal fluid leak and the leak resolved with multiple lumbar punctures.

PMID- 21743182
TI  - Falcine and parasagittal intracranial chondrosarcomas of the classical variant:
      report of two cases with review of literature.
AB  - Intracranial primary extraskeletal chondrosarcomas are extremely rare. We report
      two cases of the classical variant which were dural based: one falcine and the
      other parasagittal are presented. Only 10 cases of this variant have been
      reported in this location. The pathology and management of these lesions have
      been reviewed.

PMID- 21743183
TI  - Papillary tumor of pineal region: report of three cases and review of literature.
AB  - Papillary tumors of the pineal region (PTPRs) are rare and are recognized as a
      distinct entity in the recent 2007 World Health Organization (WHO) classification
      of tumors of nervous system. Till date, only 55 cases have been reported. We
      report another three patients of PTPRs with characteristic radiological features.
      Histologically, all the three patients exhibited remarkable uniform histology of
      epithelioid morphology with variable presence of single to multilayered papillary
      architecture. Consistent absence of fibrillary matrix was noted in all the three
      cases. None of the cases showed aggressive histology. A large multicenter study
      is essential for upfront characterizing the biological behavior, as frequency of
      these tumors is very low.

PMID- 21743184
TI  - Optic nerve fenestration in sphenoid wing meningioma.

PMID- 21743185
TI  - Spontaneous resolution of spontaneous subperiosteal orbital hematoma.

PMID- 21743186
TI  - Giant cervicothoracic ganglioneuroma.

PMID- 21743187
TI  - Cerebellar distortion after a cystoperitoneal shunt for arachnoid cyst.

PMID- 21743188
TI  - Chordoid glioma of the third ventricle: a case report with review of literature.

PMID- 21743189
TI  - Preoperative clinico-radiological diagnosis of schwannoma arising from cavernous
      segment of abducens nerve.

PMID- 21743190
TI  - Management of focal lumbar canal stenosis: importance of upright dynamic
      radiographs.

PMID- 21743191
TI  - Middle cerebral artery occlusion following autologous bitemporal fat injection.

PMID- 21743192
TI  - Reversible splenial abnormality in hypoglycemia.

PMID- 21743193
TI  - Sjogren's syndrome with chronic inflammatory demyelinating polyneuropathy.

PMID- 21743194
TI  - Head banging associated with basilar artery thrombosis.

PMID- 21743195
TI  - Paradoxical seizures and status epilepticus with newer antiepileptic drugs.

PMID- 21743196
TI  - Tako-Tsubo syndrome following status epilepticus.

PMID- 21743197
TI  - Posterior cortical atrophy: a rare visual variant of Alzheimer's disease.

PMID- 21743198
TI  - Progressive supranuclear palsy like syndrome: neurocysticercosis an unusual
      cause.

PMID- 21743199
TI  - Unique radiologic feature of spinal plasmacytoma: mini-brain appearance.

PMID- 21743200
TI  - Imaging of neurofibrolipoma of median nerve.

PMID- 21743201
TI  - Metronidazole neurotoxicity: sequential neuroaxis involvement.

PMID- 21743203
TI  - It is posterior reversible encephalopathy, and not stroke, after intravenous
      gamma globulin.

PMID- 21743204
TI  - Intracranial hemorrhage and cerebellar infarction caused by acupuncture.

PMID- 21743205
TI  - Intermittent herniation of brain causing intermittent cerebrospinal fluid
      rhinorrhea.

PMID- 21743206
TI  - Renal transplantation in developing countries.
AB  - Patients with established renal failure, living in developing countries, face
      many obstacles including lack of access to transplantation centers, quality and
      safety issues, and exploittation associated with transplant tourism. This review
      aims to determine the state and outcome of renal transplantation performed in
      developing countries and to recommend some solutions. The lack of suitable
      legislation and infrastructure has prevented growth of deceased donor programs;
      so, living donors have continued to be the major source of transplantable
      kidneys. Transplant tourism and commercial kidney transplants are associated with
      a high incidence of surgical complications, acute rejection and invasive
      infection, which cause major morbidity and mortality. Developing transplant
      services worldwide has many benefits - improving the results of transplantation
      as they would be performed legally, increasing the donor pool, making transplant
      tourism unnecessary and granting various governments the moral courage to fight
      unacceptable practices. A private-public partnership underpinned by transparency,
      public audit and accountability is a prerequisite for effective transplant
      services in the developing world. Finally, lack of dialysis facilities coupled
      with better outcomes in patients spending <6 months on dialysis prior to
      transplantation favor pre-emptive transplantation in developing countries.

PMID- 21743207
TI  - Can we improve the diagnosis of renal failure? A revised coding system for the
      Middle East and North Africa.
AB  - We reviewed the regional data on primary renal disease (PRD) causing end-stage
      renal failure (ESRF) during the decade 2000-2009. Reporting was generally
      inconsistent and diagnostic groups were poorly defined. We propose a system in
      which all diagnoses fall into one of eight broad groups: ESRF of uncertain
      etiology, congenital abnormalities of the kidney and urinary tract (CAKUT) and
      acquired uropathy, glomerular diseases, tubulo-interstitial disease (TID), other
      congenital and familial diseases, diabetes, renovascular disease and other
      specified diagnoses. Each group has sub-headings; for instance, primary
      glomerulonephritis, secondary glomerulonephritis, and hereditary glomerular
      disease. For each sub-heading, there is a list of specific diagnoses similar to
      that used by the European Dialysis and Transplant Association (EDTA) and United
      States Renal Data System (USRDS) coding systems. We also recommend that "etiology
      unknown" group should be reported in more detail as either "glomerular phenotype"
      or "tubular phenotype" and careful attention be paid to evidence for a family
      history of renal disease. To improve reporting, all patients who are diabetic,
      and all who have evidence of familial inheritance, should be recorded and a
      diagnostic category should be chosen. Thus, a diabetic patient is designated as
      "diabetic nephropathy" only if he/she fulfils the case definition for that
      diagnosis. We believe that the collection can be done much better as exemplified
      by the pediatric community, where data collection is very consistent, and there
      is a low rate of "unknown disease".

PMID- 21743208
TI  - Desensitization protocol for highly sensitized renal transplant patients: a
      single-center experience.
AB  - Highly sensitized patients are destined to remain untransplanted for long. Early
      transplantation results in cost-saving, reduced morbidity/mortality and improved
      quality of life. We carried out a prospective study to evaluate the efficacy and
      safety of desensitization protocol vis-a-vis patient/graft survival in living
      donor renal transplantation in highly sensitized patients. Between December 2008
      and April 2010, 34 renal transplant (RTx) patients underwent desensitization
      protocol. An anti-human globulin-enhanced lymphocytotoxicity crossmatch assay
      (AHG-CDC) >=25% and T-cell median channel shift (MCS) >50, B-cell MCS >100 [flow
      crossmatch (FXM)] were considered crossmatch (XM) positive. All patients were
      administered bortezomib (1.3 mg/m 2 , days 1, 4, 8, 11), plasmapheresis, rabbit
      anti-thymocyte globulin (r-ATG), mycophenolate mofetil (MMF) and intravenous
      immunoglobulins (IVIg). LCXM and FXM were repeated post-protocol. In the event of
      persistent sensitization, additional bortezomib cycle was repeated along with
      plasmapheresis, IVIg, calcineurin inhibitors (CNI) and rituximab. If the cross
      match (CMX) was negative or acceptable, patients underwent RTx. Post-transplant
      immunosuppression consisted of prednisone, CNI and MMF. Biopsy was performed in
      the event of graft dysfunction and treated accordingly. There were 18 males and
      16 females, with a mean age of 37.4 years. Mean dialysis duration was 14.9 +/-
      17.6 months. Average third party transfusions were 6.2 +/- 4.5, 17.6% had
      autoimmune diseases, 20.6% were multi-para. Pre-protocol AHGXM was 55.3 +/-
      24.5%, T-cell crossmatch (TCXM) was 122.4 +/- 91.4 MCS and B-cell crossmatch
      (BCXM) was 279 +/- 142.9 MCS. Totally, 85.3% responded within 1 month with
      reduction in AHG-CDC to 19.9 +/- 5.2%, TCXM to 24.7 +/- 19.4 MCS and BCXM to 74.7
      +/- 34.8 MCS. Side effects noted in 38.2% were manageable. Over follow-up of 0.92
      +/- 0.8 years, patient/graft survival was 100%/88.2% and mean serum creatinine
      was 1.27 +/- 0.32 mg/dL. Acute rejections were noted in 24.1%, who responded to
      steroids + rabbit antithymocyte globulin (rATG). Five (14.7%) patients were
      transplanted after changing donors. Our desensitization protocol seems to be safe
      and effective. Bortezomib may offer new possibilities in desensitization
      protocols.

PMID- 21743209
TI  - Prognosis of HTLV-1 positive renal transplant recipients in Iran.
AB  - The human T lymphocyte virus-1 (HTLV-1) is the responsible pathogen for diseases
      such as HTLV-1 associated myelopathy (HAM) and adult T-cell leukemia (ATL).
      Mashhad, in northeast Iran, with high instances of this infection, has a
      noticeable number of infected renal failure patients. Since immunosuppressive
      drugs might decrease the latency period of HTLV-1 or increase its complications,
      the question arises whether HTLV-1 positive renal failure patients are suitable
      candidates for kidney transplants. To answer this, HTLV-1 positive recipients
      were evaluated in our study. Patients were divided into two groups. First group
      consisted of patients at the Imam Reza Hospital dialysis center. Second group had
      20 kidney transplantation recipients consisting of ten infected and ten
      uninfected recipients as control from Imam Reza. Medical history of these
      patients was recorded and evaluated. The follow-up periods were between one and
      six years. Among them, 3.8% of patients undergoing dialysis were infected. The
      most important fact resulting from this study is that none of the infected
      recipients suffered from HAM or ATL during the follow-up period. In addition, it
      did not show any significant difference in the incidence of post-transplant
      complications between the infected and non-infected groups. Our study indicates
      that HTLV-1 positive patients may undergo kidney transplant without fear of
      increased incidence of side effects than those found in uninfected recipients.
      Because of short-term follow-up, probable long latency period of the virus, and
      the limited number of infected recipients, further work on this issue would be
      prudent.

PMID- 21743210
TI  - Nutritional assessment of patients on hemodialysis in a large dialysis center.
AB  - Management of the nutritional aspects of chronic kidney disease (CKD) presents a
      number of challenges. This study was performed to assess the nutritional status
      among patients on maintenance hemodialysis at the Prince Salman Center for Kidney
      Diseases, Riyadh, Saudi Arabia. The study included 200 patients with a mean age
      of 50 +/- 16 years; there were 108 males (54%) and 92 females (46%). Nutritional
      assessment was made by the Subjective Global Assessment (SGA) score. In the
      present study, 4% of the patients were found to be underweight, 49% had average
      weight, 27.5% were overweight, 14% were obese, and 5.5% had morbid obesity.
      Severe malnutrition by SGA significantly correlated with duration on dialysis,
      functional capacity, and associated co-morbid diseases. The number of patients
      included in this study was small and we recommend multi-center studies with a
      larger number of patients for better evaluation. Also, we recommend a survival
      trial to evaluate the relationship between low serum albumin and patient survival
      in the Saudi population.

PMID- 21743211
TI  - Anti-ENA antibody profile in hepatitis C patients undergoing hemodialysis.
AB  - Infection with hepatitis C virus (HCV) is increasing all over the world,
      especially among hemodialysis patients. HCV is one of the major autoantibody
      inducing viruses, where anti-nuclear antibodies (ANA), anti-smooth muscle
      antibodies (ASMA), anti-liver kidney microsome antibodies (LKM-1), and rheumatoid
      factor (RF) have been related to HCV. Few studies have investigated the presence
      of anti-extractable nuclear antigens (ENA) antibodies in chronic liver diseases,
      especially in chronic hepatitis C cases, but none investigated its
      immunostimulation role in hemodialysis units. The aim of the study was to assess
      the prevalence of HCV among chronic kidney disease- Stage 5 (CKD5) patients
      undergoing hemodialysis and the prevalence of ENA antibodies among them. Sera of
      134 patients with chronic kidney disease undergoing hemodialysis, were screened
      for HCV antibodies and ENA antibodies profile, using ELISA and Immunoblot
      technique. 41 HCV-positive blood bank donors were used as controls. Sixty-four
      (47.7%) of 134 patients undergoing hemodialysis were infected with HCV. Thirty
      three (51.6%) of 64 patients with HCV infection undergoing hemodialysis had anti
      ENA antibodies: 9 (27.3%) showed anti-SSA antibodies and 22 (66.7%) had anti-SSB
      antibodies. The prevalence of anti-ENA antibodies was significantly higher in the
      patients with HCV infection, undergoing hemodialysis, compared with both control
      groups (hepatitis C-positive blood bank donors and hepatitis C-negative patients
      undergoing hemodialysis). Seventeen of 33 HCV antibodies-positive males
      undergoing hemodialysis had anti-ENA antibodies, compared with 16 of 31 females,
      indicating no sex related difference. This study emphasizes the high prevalence
      of HCV infection in our hemodialysis patients, comparable to that of other Middle
      Eastern countries, but higher than Western ones. A strong association was
      observed between anti-HCV positivity and hemodialysis duration, as well as anti
      ENA antibody profile. However, these antibodies were gender independent.

PMID- 21743212
TI  - Dyslipidemia in dialysis patients.
AB  - In order to evaluate the lipid profiles of dialysis patients, we retrospectively
      reviewed all the chronic kidney disease (CKD) patients on chronic hemodialysis
      (HD) or continuous ambulatory peritoneal dialysis (CAPD), followed up between
      June 2004 and May 2005, in two tertiary hospitals in Riyadh, Saudi Arabia. There
      were 380 patients including 206 (54.2%) females and the mean age of the patients
      was 45.9 +/- 15.8 years. The mean dialysis duration was 65.0 +/- 58.3 months.
      Diabetes was present in 97 (25.5%) of the patients and hypertension in 84
      (22.1%). Younger patients had more disturbed lipid profile than elderly patients,
      and females had higher lipid values than males. The CAPD patients had worse lipid
      profile than those on HD, irrespective of age, sex and duration of dialysis. The
      presence of diabetes, hypertension, smoking and cardiovascular disease (CVD) all
      contributed to the worsening of lipid profiles of our patients. Dialysis patients
      showed improvement in lipid profile initially followed by gradual deterioration.
      We conclude that dyslipidemia, which increases the risk of CVD by increasing
      atherogenesis, progresses over time in dialysis patients and becomes worse in
      CAPD patients.

PMID- 21743213
TI  - Factors predicting malnutrition in hemodialysis patients.
AB  - Signs of protein-energy malnutrition are common in maintenance hemodialyis (HD)
      patients and are associated with increased morbidity and mortality. To evaluate
      the nutritional status and relationship between various parameters used for
      assessing malnutrition, we performed a cross-sectional study in 37 HD patients
      treated with thrice weekly sessions for at least two weeks. Global nutritional
      status was evaluated by the dual-energy X-ray absorptiometry (DEXA) scan. Body
      weight and several laboratory values, including serum albumin (Salb), serum
      prealbumin, bicarbonate, cholesterol, serum C-reactive protein (SCRP), and
      hemoglobin, were recorded. Dose of dialysis was evaluated by urea kinetic
      modeling. The patients were subdivided into two groups based on body mass index:
      group I, normal nutritional status (71%) and group II, malnutrition (29%). The
      clinical factors associated with malnutrition included advanced age and cardio
      vascular diseases (CVD), decreased fat mass (FM) measured by DEXA, low Salb and
      prealbumin, and severe anemia. The Salb level was not only a predictor of
      nutritional status, but also was independently influenced by age and SCRP, which
      was more common in malnourished patients than in patients with normal nutritional
      status. Both low Kt/V and less weekly dialysis time were associated with
      malnutrition. The FM and lean body mass (LBM) calculated by DEXA correlated with
      CVD and other markers of malnutrition (Salb, total cholesterol).

PMID- 21743214
TI  - Artificial neural network for prediction of equilibrated dialysis dose without
      intradialytic sample.
AB  - Post-dialysis urea rebound (PDUR) is a cause of Kt/V overestimation when it is
      calculated from pre-dialysis and the immediate post-dialysis blood urea
      collections. Measuring PDUR requires a 30-or 60-min post-dialysis sampling, which
      is inconvenient. In this study, a supervised neural network was proposed to
      predict the equilibrated urea (C eq) at 60 min after the end of hemodialysis
      (HD). Data of 150 patients from a dialysis unit were analyzed. C eq was measured
      60 min after each HD session to calculate PDUR, equilibrated urea reduction rate
      eq (URR), and ( eq Kt/V). The mean percentage of true urea rebound measured after
      60 min of HD session was 19.6 +/- 10.7. The mean urea rebound observed from the
      artificial neural network (ANN) was 18.6 +/- 13.9%, while the means were 24.8 +/-
      14.1% and 21.3 +/- 3.49% using Smye and Daugirdas methods, respectively. The ANN
      model achieved a correlation coefficient of 0.97 (P <0.0001), while the Smye and
      Daugirdas methods yielded R = 0.81 and 0.93, respectively (P <0.0001); the errors
      of the Smye method were larger than those of the other methods and resulted in a
      considerable bias in all cases, while the predictive accuracy for ( eq Kt/V) 60
      was equally good by the Daugirdas' formula and the ANN . We conclude that the use
      of the ANN urea estimation yields accurate results when used to calculate ( eq
      Kt/V).

PMID- 21743215
TI  - Prevalence of mixed hepatitis C virus (HCV) genotypes among recently diagnosed
      dialysis patients with HCV infection.
AB  - Hepatitis C virus (HCV) infection is considered a major health problem recognized
      globally. HCV is a major cause of chronic liver disease that may lead to
      cirrhosis and hepatocellular carcinoma. The aim of this study was to investigate
      the prevalence of multiple (mixed) HCV genotypes in Saudi patients recently
      diagnosed with HCV infection and their association with various clinical risk
      factors. We examined a total of 1,292 newly diagnosed HCV-positive cases between
      January 2006 and July 2009 at the Molecular Pathology Laboratory, King Abdulaziz
      Medical City, Riyadh. The clinical and laboratory data of the study patients were
      collected. The HCV-RNA viral load and its genotyping were carried out with RT-PCR
      technology to assist in the follow-up and management of HCV-infected patients
      undergoing antiviral therapy. Twenty-two patients (1.7%) were found to have mixed
      HCV genotypes; of them, mixed genotypes associated with genotype-4 were seen in
      19 patients (86%), mixed genotypes associated with genotype-1 were found in
      68.4%, with genotype-3 in 26.3% and with genotype-2 in 5.3%. Additionally, mixed
      genotypes associated with genotype-1 were seen in three cases (13.6%); they were
      associated with genotype-2 in two (66.7%) and with genotype-5 in one patient
      (33.3%). In conclusion, the prevalence rate of mixed HCV genotypes in the cohort
      of the newly infected Saudi patients was 1.7%, with genotype-4 being the most
      frequent genotype encountered.

PMID- 21743216
TI  - The influence of increased peritoneal membrane surface area on dialysis adequacy.
AB  - The adequacy of peritoneal dialysis is generally dependant on the choice of
      peritoneal fluid, the intraperitoneal fill volume and the contact time. Moreover,
      the peritoneal surface area acts as a major factor in the exchange dynamics of a
      peritoneal membrane. We designed a mechanism to increase the membrane surface
      contact area by using an abdominal belt in order to exert enough pressure on the
      fill volume, to effectively recruit more area in contact for exchange. We studied
      12 patients on regular continuous ambulatory peritoneal dialysis (CAPD) at our
      center from January to October 2008. The age of patients ranged from 44 to 75
      years, with a median of 55 years. All the patients were maintained on the same
      prescription four months before and during the study. Dialysis solutions were
      1.36% Deaneal(r) , two liters, three exchanges and the last fill volume was two
      liters 7.5% Extraneal(r) . The belt was applied to all the patients most of the
      day and all night. We then observed its effect on dialysis adequacy, reflected by
      various parameters over a period of eight months. The average Kt/V before wearing
      the belt was 1.89 and improved after applying the belt to 2.3 (P <0.05). Our
      study suggests that increasing the abdominal pressure by wearing an abdominal
      belt rendered the filling volume of the PD dialysate to have a better contact
      with the peritoneal membrane and improved the dialysis adequacy. Studies with
      larger sample size are required to confirm the results.

PMID- 21743217
TI  - Growth indices in urinary tract infection children with or without vesicoureteral
      reflux.
AB  - To determine the growth quality in children, less than 5 years of age, affected
      with urinary tract infection (UTI) and to compare the indices between patients
      with and without vesico-ureteral reflux (VUR) based on their reflux severity
      and/or laterality, we studied 106 children less than 5 years of age with UTI at
      Imam Reza Hospital of Kermanshah, Iran, and divided the study group into four
      subgroups based on their cystouretrography results as follows: Group 0: without
      reflux (as control group); Group 1: mild VUR; Group 2: moderate VUR; and Group 3:
      severe VUR. In all the subgroups, weight height index (WHI) was lower than 100%
      and was 96%, 93%, 95%, and 98%, respectively. We found no correlation between
      reflux severity and WHI in all the subgroups. In addition, the difference in the
      mean height standard deviation score (HSDS) (0.10, -0.12, -0.19, and -0.22,
      respectively) in the different subgroups was statistically insignificant. The
      mean WHI in the group with unilateral and bilateral reflux was 94.5% +/- 8.9% and
      95.0% +/- 8.16%, respectively, while the mean HSDS was -0.16 +/- 0.35 and -0.18
      +/- 0.38, respectively, and the difference was statistically insignificant in
      both the cases. We conclude that in children with UTI and normal glomerular
      filtration rate, the existence of reflux with all grades of severity and
      laterality exerts no impact on the growth index.

PMID- 21743218
TI  - Poor prognostic factors of lupus nephritis.
AB  - The occurrence of renal involvement during the clinical course of systemic lupus
      erythematous (SLE) is generally considered to be the most important factor
      influencing the prognosis in terms of morbidity and mortality. The factors
      influencing prognosis in lupus nephritis (LN) are variable in literature. Our aim
      was to determine predictive factors of poor prognosis in LN among our population.
      In this retrospective study, 82 cases of LN observed over 18 years were studied.
      There were 12 males and 70 females with a mean age of 26.9 +/- 11 years. At
      presentation, the mean proteinuria was 3.9 +/- 4 g/day; the nephrotic syndrome,
      hematuria, leukocyturia and renal failure were observed in 67.1%, 63.4%, 56.1%
      and 37.8% of cases, respectively. LN was of class I, II, III, IV and V in 4.9%,
      13.4%, 23.2%, 50% and 8.5% of the cases, respectively. Fifteen patients developed
      end-stage renal failure and/or died. The presence of hypertension, renal failure,
      massive proteinuria and high activity index score of LN was associated with poor
      renal prognosis.

PMID- 21743219
TI  - Microalbuminuria in children with sickle cell anemia.
AB  - Microalbuminuria (MA) is an early marker of various diseases affecting the renal
      system. Its relevance in children with sickle cell anemia (SCA), who are known to
      be prone to renal complications, has not been fully explored, particularly in the
      study locale. Besides, its occurrence in this group of patients remains under
      reported in locations where the burden of SCA is enormous. To assess its
      prevalence in this cohort, 69 children with sickle cell anemia (in their steady
      state), aged 1-16 years, were consecutively enrolled and evaluated. The study,
      spanning from November 2006 to February 2007, was cross-sectional and
      descriptive. Employing a semiquantitative method, MA in an early morning spot
      urine sample was determined in each subject. Also evaluated were the
      anthropometry, blood pressure (BP) and packed cell volume. Prevalence of MA in
      the study subjects was 20.3%. Though not significant, prevalence of MA was more
      in females (25.9%) than in males (16.7%). Prevalence of MA increased with
      increasing age and was also significantly associated with weight (P = 0.033), but
      was independent of family history of hypertension. BP recordings, both systolic
      and diastolic, in the study subjects were within normal range. MA occurs
      significantly enough in children with SCA to warrant routine screening for it.
      Such a measure could assist in the early detection of ensuing renal complications
      and can pave way for improved management of a sickler who is particularly prone
      to such problems. In addition, interventional measures, known to retard rate of
      deterioration of kidney function due to prolonged proteinuria, could also be
      instituted early.

PMID- 21743220
TI  - Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of urinary
      protein in acute kidney injury.
AB  - Recent experimental and clinical studies have shown the importance of urinary
      proteomics in acute kidney injury (AKI). We analyzed the protein in urine of
      patients with clinical AKI using sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) for its diagnostic value, and followed them up for 40
      months to evaluate prognosis. Urine from 31 consecutive cases of AKI was analyzed
      with SDS-PAGE to determine the low, middle and high molecular weight proteins.
      Fractional excretion of sodium (FENa) was estimated from serum and urine
      creatinine and sodium (Na). The cases were followed-up for 40 months from the end
      of the recruitment of study cases. Glomerular protein was higher in the hematuria
      group when compared with the non-hematuria group (P <0.04) and in the AKI group
      than in the acute on chronic renal failure (AKI-on-CRF) group (P <0.002). Tubular
      protein was higher in the AKI-on-CRF group (P <0.003) than in the AKI group.
      Tubular protein correlated with FENa in groups with diabetes mellitus (DM), AKI
      on-CRF, and without hematuria (P <0.03, P <0.02 and P <0.004, respectively).
      Pattern of protein did not differ between groups with and without DM and clinical
      acute tubular necrosis (ATN). At the end of 40 months follow-up, category with
      predominantly glomerular protein progressed to chronic renal failure (CRF) or end
      stage renal failure in higher proportion (P <0.05). In clinical AKI, we observed
      that glomerular protein dominated in cases with glomerular insult, as indicated
      by hematuria. Tubular protein was common in the study cases with CRF, DM and
      cases without hematuria. This indicates tubulo-interstitial injury for AKI in
      these cases. Patients with predominantly glomerular protein had an adverse
      outcome.

PMID- 21743221
TI  - Percutaneous ultrasound-guided renal biopsy.
AB  - This study was done to assess the safety and efficacy of real-time ultrasound
      guided percutaneous renal biopsy (PRB) and to determine the optimal period of
      observation required as well as to ascertain the risk factors for any ensuing
      complications. Between 1 st February 2006 and 31 st January 2008, a total of 86
      PRBs were performed by the radiologist using an automated biopsy gun with 16
      gauge needle at the National Organ Transplant Centre, Central Hospital, Tripoli,
      Libya. Prior to the procedure coagulation profile was done in all the patients.
      All patients were kept on strict bed rest for 6-hours post-procedure. Of the 86
      renal biopsies performed, 78 patients were referred from Rheumatology Department
      and 8 were post-kidney transplant recipients. There were 23 males with age
      ranging from 15 to 56 years and 63 females with age ranging from 16 to 66 years.
      A mean of 17.5 glomeruli were present in each specimen. A glomerular yield of
      less than five glomeruli was seen in only four biopsies. Class I lupus nephritis
      (LN) was seen in one patient, class II LN in seven patients, class III LN in 13
      patients and class IV LN in 29 patients. All the eight renal allografts were
      diagnosed as either acute tubular necrosis or acute interstitial rejection. The
      overall complication rate was 5.8% and these complications were observed within 6
      hours of biopsy. No late complications were seen. PRB under real-time ultra-sound
      guidance is a safe and efficacious procedure to establish the histological
      diagnosis of the renal disease and may be done as an out-patient procedure. A
      post-biopsy observation time of 6 hours appears to be optimal.

PMID- 21743222
TI  - Mucormycosis in renal transplant recipients: predictors and outcome.
AB  - Mucormycosis, though uncommon, is associated with high mortality in transplant
      recipients. This study was conducted to assess the incidence and risk factors
      associated with mucor infection and its outcome. We retrospectively reviewed the
      hospital records for evidence of mucor infection in patients transplanted between
      January 2005 and December 2009 at the Department of Nephrology and Clinical
      Transplantation (IKDRC), Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat,
      India. The patient demographics, symptoms, diagnostic techniques and outcomes
      were analyzed. Out of a total of 1,330 transplants, 16 patients (1.20%) had
      evidence of mucor infection, including 14 males and two females. The mean age of
      the patients was 43.8 years. The time interval between transplantation and
      disease onset varied greatly (range: 1 month to 7 years; median 13.8 months). The
      presenting symptoms were fever (87.5%), severe headache (56.2%), facial swelling
      (56.2%), watering of eyes (56.2%), cough (31.2%), respiratory distress (18.7%)
      and pain abdomen (12.5%). Suspected patients were evaluated by computerized
      tomographic (CT) scan/magnetic resonance imaging (MRI), bronchoalveolar lavage
      (BAL) and biopsy, and the diagnosis was confirmed by culture. Of the 16 patients
      studied, nine had rhinocerebral mucormycosis, five had pulmonary mucormycosis and
      one case each had infection at the graft anastmosis site and disseminated
      mucormycosis. Early and intensive treatment with liposomal amphotericin-B was
      instituted in all patients, and extensive debridement was performed in addition
      in 11 cases, and one patient was subjected to graft nephrectomy; 10 patients
      (62.5%) survived. Our study suggests that rhinocerebral is the most frequent site
      of mucormycosis and it can occur very early or late in the post-transplant
      period. Early diagnosis and combined surgical debridement and parenteral
      liposomal amphotericin-B along with reduction of immunosuppression improve the
      patient survival.

PMID- 21743223
TI  - Combined liver and kidney transplantation in a highly sensitized and positively
      cross-matched patient.
AB  - Combined liver kidney transplantation (CLKT) has been used on many occasions and
      proved to be a successful event for both liver and kidney in highly sensitized
      patients. Our aim was to review the immunological and other laboratory results of
      a CLKT in a highly sensitized patient. CLKT was used to treat a highly
      sensitized, 42-year-old female. She was suffering from end-stage liver disease
      due to hepatitis C virus (HCV) infection and renal disease due to diabetic
      nephropathy. Cross-matching, panel reactive assay (PRA) and routine laboratory
      tests for liver and renal function were carried out before and after the CLKT.
      Prior to the CLKT, the patient was highly sensitized with human leukocytes
      antigens (anti-HLA) class I antibodies (>90%). Patient was offered CLKT from a
      deceased donor. She had donor-specific antibodies, class I and II. Both T and B
      CDC cross-matches (XM) were positive pre-transplant and eight hours post
      transplant. Both cross-match and PRA results became completely negative six days
      post CKLT. Almost 30 months post CLKT, her renal function is normal and negative
      for class I and II PRA. Liver graft appears to be protective for renal graft when
      they are combined even in highly sensitized patients. CLKT is very useful in
      overcoming sensitization in addition to treating end-stage liver and renal
      diseases.

PMID- 21743224
TI  - Hemodialysis catheter related rhodococcus bacteremia in immunocompetent host.
AB  - Rhodococcus equi (R. equi) is an uncommon cause of infection in immunocompetent
      individuals. We describe a case of R. equi bacteremia associated with
      hemodialysis (HD) catheter in an immunocompetent patient. A 38-year-old female
      with end-stage renal disease (ESRD) of uncertain etiology, on HD for the past 15
      months who was previously healthy otherwise, was admitted with the complaints of
      intermittent fever, mild nausea and occasional vomiting for two weeks. Last HD
      was performed four days earlier through a tunneled right internal jugular
      permacath. Clinically the patient was afebrile and in no acute distress. She was
      hemodynamically stable with no peripheral stigmata of an endovascular infection.
      Physical examination was essentially normal. Initially, the patient was treated
      with intravenous vancomycin with each HD, retaining the catheter. However, due to
      persistently positive blood cultures, HD catheter had to be removed. The patient
      became afebrile and nausea and vomiting resolved. She improved clinically, and
      repeated surveillance blood cultures done after the removal of catheter were
      reported negative. Subsequently, a new HD catheter was inserted for her. Although
      R. equi is an uncommon cause of infection in immunocompetent individuals, it does
      occur with considerable mortality and morbidity, and a high index of clinical
      suspicion is required to recognize this infection in immunocompetent individuals.

PMID- 21743225
TI  - Severe hypoglycemia in peritoneal dialysis patients due to overestimation of
      blood glucose by the point-of-care glucometer.
AB  - Although overestimation of blood glucose (BG) by certain glucometers in
      peritoneal dialysis (PD) patients has been reported, awareness of this problem by
      healthcare providers of multiple disciplines and different specialties is
      probably insufficient. This is a case series of four patients who had severe
      symptomatic hypoglycemia and normal BG by point-of-care glucometer at a tertiary
      care center from December 2007 to September 2008. We report four insulin-treated
      diabetic patients (age = 58.2 +/- 16.2 years, 3 men and 1 woman) on PD, who had
      acute decrease in level of consciousness in the emergency department (n = 1) and
      the hospital ward (n = 3). While they had their symptoms, they all had normal BG
      measured by the Accuchek glucometer (7.1 +/- 3.3 mmol/L); nonetheless,
      simultaneous or near-simultaneous laboratory-measured BG levels were very low
      (2.0 +/- 1.3 mmol/L). The mean difference in BG was 5.8 mmol/L (12 simultaneous
      or near-simultaneous measurements). Three patients had icodextrin-based PD in the
      night before symptomatic hypoglycemia. The first two patients, whose treatment
      for hypoglycemia was delayed, remained comatose and died later. The latter two
      patients were promptly treated with intravenous dextrose and did not have any
      neurologic sequelae. One of them died later from multiple organ failure. Over
      estimation of BG in peritoneal dialysis patients by certain point-of-care
      glucometers is a serious problem and can be fatal. Increased awareness of this
      problem for all healthcare providers and use of appropriate glucometers are
      required.

PMID- 21743226
TI  - HIV-associated immune complex glomerulonephritis with "lupus-like" features.
AB  - Renal structural abnormalities in HIV/AIDS infected patients have been
      infrequently and incompletely reported in patients from sub-Saharan Africa. We
      report an immune complex glomerulonephritis with "lupus-like" features in a ten
      year-old HIV+ boy who was evaluated at the University Hospital of Kinshasa. The
      light microscopic examination of the renal biopsy displayed a predominantly
      membranoproliferative glomerulonephritis with prominent focal segmental
      necrotizing injury, numerous wire-loops, and a spiky membranous nephropathy. In
      addition, there were prominent tubular injury, microcysts filled with periodic
      acid-Schiff (PAS) positive casts, edema and an inflammatory infiltrate of the
      interstitium, features of a classic HIV-associated nephropathy (HIVAN). Electron
      microscopy revealed large subendothelial, intra-membranous, subepithelial and
      mesangial deposits. The combination of these findings, while being consistent
      with lupus nephritis WHO grade IV/V, the tubulointerstitial HIVAN-like changes
      and the absence of clinical evidence of lupus disease favored an HIV-associated
      immune complex glomerulonephritis with "lupus-like features".

PMID- 21743227
TI  - Multicystic nephroma masquerading as Wilms' tumor: a clinical diagnostic
      challenge.
AB  - Multicystic nephroma (MCN) is an uncommon, non-heritable, unilateral, benign
      tumor that represents 2-3% of all primary renal tumors in the pediatric age
      group. It is characterized by bimodal age incidence with 50% of cases seen in
      children less than four years of age. Presented here is an 8-month-old boy with
      asymptomatic, gradually progressive renal lump of two months duration, with no
      other complaints. Ultrasound of the abdomen showed a well-defined multi-septated
      cystic mass involving whole of the kidney. Computerized Tomography (CT) scan
      revealed a unilateral cystic lesion involving almost the entire left kidney.
      Keeping in mind the age, clinical presentation and radiological appearance, the
      possibility of cystic variant of Wilms' tumor could not be ruled out pre
      operatively. An elective left nephrectomy was done. The histopathological report
      revealed MCN of the left kidney. Only a few cases have been reported from India.
      We report here one such pediatric case.

PMID- 21743228
TI  - Cystic renal neoplasm causing hypertension in a 2-year-old child.
AB  - Cystic neoplasms of kidney in pediatric age group include a wide variety of
      tumors, both of benign and malignant pathology. In a child, renal neoplasms with
      associated hypertension are rare. Here, we present a 2-year-old child who had a
      multicystic renal tumor with hypertension. She underwent radical nephrectomy
      subsequent to which hypertension disappeared. The postoperative pathology
      revealed multicystic nephroma.

PMID- 21743229
TI  - Long neglected neurogenic bladder.
AB  - Urinary diversion is indicated for the management of the neurogenic bladder.
      However, there is a risk for developing pyocystitis in this type of patients. We
      present a case of young female who presented with a history of frequent urinary
      tract infection (UTI) post urinary diversion for neurogenic bladder. Ever since
      she underwent simple cystectomy, there have been no further episodes of UTI.

PMID- 21743230
TI  - Necrotic crescentic glomerulonephritis and IGA nephropathy: Lee-Haas
      classification revisited.
AB  - Capillary necrosis is frequently encountered in most forms of proliferative
      glomerulonephritis, and varies in severity from only occasional finding to severe
      form of glomerular vasculitis. We report a patient who presented with features of
      acute glomerulonephritis. Kidney biopsy showed crescents in 30% of the glomeruli,
      diffuse mesangial expansion and hypercellularity with IgA deposits on
      immunofluorescence. The relevance of the Lee-Haas classification is discussed in
      relation to assessing prognosis.

PMID- 21743231
TI  - Joubert syndrome with nephronophthisis in neurofibromatosis type 1.
AB  - Joubert syndrome (JS) is a rare developmental disorder of the central nervous
      system, characterised by brainstem and cerebellar malformations, hypotonia,
      episodic hyperapnea and apnea and mental retardation. It may be associated other
      systemic abnormalities like ocular (e.g., retinal dysplasia, etc.), oculomotor,
      musculoskeletal and renal (e.g., cystic dysplasia, nephronophthisis), with renal
      failure. We describe a case of JS with nephronophthisis in neurofibromatosis Type
      1 leading to end-stage renal disease, a association that has never been described
      earlier in the medical literature to the best of our knowledge.

PMID- 21743232
TI  - ADAMTS-13 deficiency following Hemiscorpius lepturus scorpion sting.
AB  - Hemiscorpius lepturus is a lethal scorpion with potentially cytotoxic venom.
      Various degrees of local and systemic toxicity have been observed after its
      envenomation ranging from local erythema to disseminated intravascular
      coagulation, renal failure and severe pulmonary hemorrhage. In this case report,
      we report on a seven-year-old patient who developed the hemolytic uremic syndrome
      (HUS) after being stung by the scorpion H. lepturus. This condition is
      characterized by microangiopathic hemolytic anemia, thrombocytopenia, increased
      serum levels of lactate dehydrogenase and uremia. We evaluated the causes of HUS
      and found that the levels of C3, C4, CH50 and H factors were normal, but the
      activity of Von Willebrand factor cleaving protease was decreased (less than 5%
      of the normal activity). The patient improved after administering therapy with
      plasma exchange.

PMID- 21743233
TI  - A page in transplantation.

PMID- 21743234
TI  - Effect of post-transplant weight at one year on renal allograft function.

PMID- 21743235
TI  - Vascular access surgery: excellent success rates with the use of a vascular
      dilator.

PMID- 21743236
TI  - Tumor marker and hemodialysis.

PMID- 21743237
TI  - The seroprevalence of anti-HCV in high-risk dialysis patients.

PMID- 21743238
TI  - Epidemiology of hepatitis C in the Middle East: all available data.

PMID- 21743239
TI  - Hypophosphatemia in peritoneal dialysis patients.

PMID- 21743240
TI  - Mesenteric cavernous hemangioma in a cryptorchid man.

PMID- 21743241
TI  - Renal biopsy findings in lupus nephritis.

PMID- 21743242
TI  - Why does kidney allograft fail? A long-term single-center experience.
AB  - We studied the characteristics and the predictors of survival in Bahraini renal
      transplant recipients with an allograft that functioned for more than 10 years.
      Seventy-eight patients underwent renal transplantation between 1982 and 1999.
      Among them, 56 patients maintained functioning allografts for more than 10 years
      (range 10-30 years). Characteristics of the surviving patients, data on graft
      survival, and determinants of outcome were obtained by reviewing all medical
      records. The mean age at time of renal transplantation was 33.6 +/- 15.3 years.
      The source of the graft in 42 (75%) recipients was from living related donors
      with a mean age of 31.4 +/- 7.7 years, and it was the first graft in 48
      recipients. The primary immunosuppression regimen consisted of cyclosporine (CsA)
      and prednisolone. Azathioprine (AZA) was given to 52 (92.9%) recipients, while
      four patients received steroids and AZA only. Induction therapy was administered
      to 30 patients in the CsA group. Acute rejection episodes occurred in eight
      (14.3%) patients, of whom two experienced two episodes. During the last follow-up
      in January 2010, the mean serum creatinine was 118.3 +/- 46.5 MUmol/L. A history
      of cancer was noted in one patient, whereas hypertension was encountered in 54%
      and diabetes mellitus in 20.5%. We compared the graft functioning group with the
      graft failure group and found that the independent determinants of long-term
      graft survival included time of late acute rejection episodes and histopathologic
      findings of chronic allograft damage, post-transplant hypertension and serum
      creatinine at one year. We conclude that renal transplantation even in its
      earliest years and despite the associated numerous complications has provided a
      ten-year or more of near-normal life to patients with end-stage renal disease.

PMID- 21743243
TI  - Acute kidney injury in a teaching hospital in Oman.
AB  - To determine the incidence, etiology and outcome of acute kidney injury (AKI) at
      a teaching hospital in Oman, we studied all adult cases that developed AKI at our
      hospital from July 2006 to June 2007. Data from the hospital information system
      (HIS) for all adult admissions in the wards and intensive care units for the
      study period were obtained, and included baseline serum creatinine, serum
      creatinine on the day of diagnosis, peak serum creatinine, urine output in the
      last six and 12 hours at the time of diagnosis, etiology of acute renal failure,
      presence of any co-morbid conditions, and renal replacement therapy and outcome.
      Of the 19,738 adult admissions, there were 108 episodes of AKI in 100 patients.
      The incidence of acute renal failure was 0.54%. The etiology of AKI was pre-renal
      in 55 (50.9%), obstructive in 5 (4.6%) and acute tubular necrosis (ATN) in the
      remaining 48 (44.4%) patients. Renal replacement therapy (RRT) was required in
      24.1% of cases. Of the patients who developed AKI, 36 (33.33%) died during same
      hospital admission, 37 (34.26%) recovered to discharge with no renal impairment,
      32 (29.63%) recovered with residual renal impairment and 2 (1.85%) recovered with
      dialysis dependence.

PMID- 21743244
TI  - Acute renal failure in Yemeni patients.
AB  - Acute renal failure (ARF) is defined as a rapid decrease in the glomerular
      filtration rate, occurring over a period of hours to days. The Science and
      Technology University Hospital, Sana'a, is a referral hospital that caters to
      patients from all parts of Yemen. The aim of this study is to have a deeper
      overview about the epidemiological status of ARF in Yemeni patients and to
      identify the major causes of ARF in this country. We studied 203 patients with
      ARF over a period of 24 months. We found that tropical infectious diseases
      constituted the major causes of ARF, seen in 45.3% of the patients. Malaria was
      the most important and dominant infectious disease causing ARF. Hypotension
      secondary to infection or cardiac failure was seen in 28.6% of the patients.
      Obstructive nephropathy due to urolithiasis or prostate enlargement was the cause
      of ARF in a small number of patients. ARF was a part of multi-organ failure in
      19.7% of the patients, and was accompanied by a high mortality rate. Majority of
      the patients were managed conservatively, and only 39.9% required dialysis. Our
      study suggests that early detection of renal failure helps improve the outcome
      and return of renal function to normal. Mortality was high in patients with
      malaria and in those with associated hepatocellular failure.

PMID- 21743245
TI  - HLA polymorphism in Sudanese renal donors.
AB  - The main objective of this study is to provide a database for renal
      transplantation in Sudan and to determine the HLA antigens and haplotype
      frequencies (HFs) in the study subjects. HLA typing was performed using the
      complement-dependant lymphocytotoxicity test in 250 unrelated healthy individuals
      selected as donors in the Sudanese Renal Transplantation Program. Considerable
      polymorphism was observed at each locus; A2 (0.28), A30 (0.12), A3 (0.09), A24
      (0.09), A1 (0.09), and A68 (0.06) were the most frequent antigens in the A locus,
      while B51 (0.092), B41 (0.081), B39 (0.078), B57 (0.060), B35 (0.068), B 50
      (0.053) and B 52 (0.051) were the most common B locus antigens. DR13 (0.444) and
      DR15 (0.160) showed the highest antigen frequencies (AFs) in the DR locus. In the
      DQ locus, DQ1 showed the highest gene frequency (0.498), while DQ2 and DQ3 AFs
      were (0.185) and (0.238), respectively. The most common HLA-A and -B haplotypes
      in positive linkage disequilibrium were A24, B38; A1, B7; and A3, B52. The common
      HLA-A and -B HFs in positive linkage disequilibrium in the main three tribe
      stocks of the study subjects (Gaalia, Nile Nubian and Johyna) were A24, B38 for
      Gaalia; A24, B38 and A2, B7 for Johyna; and A2, B64 and A3, B53 for Nile Nubian.
      These results suggest that both class I and class II polymorphisms of the study
      subjects depict considerable heterogeneity, which reflects recent admixture of
      this group with neighboring Arabs and African populations.

PMID- 21743246
TI  - Laparoscopic trans-mesocolic pyeloplasty in children: initial experience from a
      center in India.
AB  - The aim of the present study is to report our experience with laparoscopic
      pyeloplasty via trans-mesocolic approach in children with left pelvi-ureteric
      junction (PUJ) obstruction. Between May 2007 and May 2008, 12 children aged
      between five and 16 years, with documented PUJ obstruction on the left side,
      underwent laparoscopic pyeloplasty via trans-mesocolic approach. The outcome was
      assessed by post-operative isotope renal scan. The mean age of the study patients
      was eight years, ranging between five and 16 years. There were five males and
      seven females in the study. All children underwent Anderson Hynes Pyeloplasty by
      a single surgeon. All cases were stented with a JJ stent for a period of six
      weeks post-operatively. The procedures were completed successfully in all
      patients without need for conversion to open pyeloplasty in any patient. The mean
      operative time was 95 min, with a range of 80-140 min. The average blood loss was
      57 mL. The mean hospital stay was 3.5 days with a range of 2.5 to six days. All
      children returned back to school within nine days following surgery. The mean
      follow-up period was 12 months (range, nine to 14 months). Eleven of the patients
      were completely asymptomatic, while one reported mild flank pain. All children
      underwent renal scans and renal ultrasound three months after stent removal. Ten
      had improved function on the scan while in one patient, the function remained the
      same and, in another, it showed obstructed response to diuretic, although the
      symptoms had improved. In all the cases, renal ultrasound showed a decrease in
      the severity of hydronephrosis by at least one degree. These results confirm that
      laparoscopic pyeloplasty by trans-mesocolic approach in children for left-sided
      PUJ obstruction is safe and feasible.

PMID- 21743247
TI  - A young man with polyuria and lethargy.
AB  - We report a 20-year-old man who presented to our emergency room with a history of
      polyuria, weakness, constipation, nausea, and vomiting of two months duration.
      History and clinical examination revealed a significant weight loss and mild
      hepatomegaly. Laboratory investigations revealed hypokalemia, hypernatremia, and
      severe metabolic acidosis and anemia. Ultra-sound of the abdomen revealed
      enlarged kidneys without hydronerphrosis. The patient developed paralysis due to
      further decline in serum potassium level, which improved after an aggressive
      fluid and electrolyte management. He was investigated extensively for polyuria
      and type of acidosis. The kidney biopsy showed interstitial leukemic
      infiltration. He was managed accordingly and recovered from the condition. This
      case demonstrates an unusual presentation of a hematological malignancy, which
      was a diagnostic as well as a management challenge.

PMID- 21743248
TI  - The onset temperature of the heat-shock response and whole-organism thermal
      tolerance are tightly correlated in both laboratory-acclimated and field
      acclimatized tidepool sculpins (Oligocottus maculosus).
AB  - We examined the relationship between thermal tolerance, measured as critical
      thermal maximum (CT(max)), and aspects of the heat-shock response in tidepool
      sculpins (Oligocottus maculosus) acclimated to constant laboratory temperatures
      or acclimatized to field conditions. The CT(max) of fish laboratory acclimated to
      6 degrees , 13 degrees , and 20 degrees C were 27.6 degrees  +/- 0.1 degrees C,
      29.5 degrees  +/- 0.1 degrees C, and 30.8 degrees  +/- 0.1 degrees C,
      respectively, increasing linearly by 0.2 degrees C for each 1 degrees C increase
      in acclimation temperature. The CT(max) of field-acclimatized fish from the low
      intertidal (29.9 degrees  +/- 0.1 degrees C) was significantly lower than that of
      fish from the mid- (30.5 degrees  +/- 0.1 degrees C) and high (30.4 degrees  +/-
      0.1 degrees C) intertidal. CT(max) and the onset temperature of hsp70 induction
      in gill (T(on)) were highly correlated in both laboratory-acclimated and field
      acclimatized sculpins, with T(on) occurring at 2 degrees C below CT(max) in all
      cases. However, there was no consistent relationship between CT(max) and the
      maximum levels of gill hsp70 mRNA. Predicted "acclimation" temperature (15.9
      degrees  +/- 0.3 degrees C) and mean habitat temperature (15.9 degrees  +/- 1.6
      degrees C) were similar for sculpins from low intertidal pools, but this
      relationship was not apparent in mid- and high intertidal fish. Mark-recapture
      experiments indicated that approximately 80% of fish from low intertidal pools
      were residents of that pool, but residency rates were less than 50% in mid- and
      high intertidal pools, which may explain the lack of correlation between CT(max)
      and habitat variables in these groups. These data indicate that gill hsp70 T(on)
      and CT(max) are highly correlated indicators of the thermal performance of
      tidepool sculpins in both laboratory and field settings.

PMID- 21743249
TI  - Thermal tolerance of Antarctic notothenioid fishes correlates with level of
      circulating hemoglobin.
AB  - The West Antarctic Peninsula region is experiencing some of the most rapid
      elevations in temperature of any marine environment. We assessed thermal
      tolerance of white- and red-blooded Antarctic notothenioid fishes inhabiting
      these waters, using a modified critical thermal maximum (CT(max)) design.
      Temperature was elevated acutely from ambient at a constant rate of 3.6 degrees C
      h(-1), and CT(max) was defined as the temperature where animals lost righting
      response. CT(max) temperatures of white-blooded icefishes Chionodraco
      rastrospinosus (13.3 degrees  +/- 0.2 degrees C) and Chaenocephalus aceratus
      (13.9 degrees  +/- 0.4 degrees C) were significantly lower than those of red
      blooded fishes Gobionotothen gibberifrons (15.5 degrees  +/- 0.2 degrees C) and
      Notothenia coriiceps (17.1 degrees  +/- 0.2 degrees C). Lepidonotothen
      squamifrons, a red-blooded species with low hematocrit, exhibited a CT(max) (14.2
      degrees  +/- 0.4 degrees C) that was significantly lower than that of the other
      red-blooded animals and similar to that of icefishes. A strong relationship
      between CT(max) and hematocrit (r(2) = 0.76) suggests that the oxygen-carrying
      capacity of blood may partially dictate acute lethal temperature. Despite a short
      treatment duration, we detected a rise in the mRNA level of hypoxia response gene
      HIF-1alpha in N. coriiceps heart tissue. One-week exposure to 4 degrees C had no
      effect on the CT(max) of N. coriiceps, indicating an inability to compensate for
      rising temperature under these experimental conditions. Our results suggest that
      icefishes are particularly sensitive to temperature elevation because of a lack
      of hemoglobin and may be a sentinel taxon for climate change.

PMID- 21743250
TI  - Molecular analysis, tissue profiles, and seasonal patterns of cytosolic and
      mitochondrial GPDH in freeze-resistant rainbow smelt (Osmerus mordax).
AB  - Rainbow smelt (Osmerus mordax) is an anadromous teleost that, beginning in late
      fall, accumulates plasma glycerol in excess of 200 mM, which subsequently
      decreases in the spring. The activity of cytosolic glycerol-3-phosphate
      dehydrogenase (cGPDH) is higher (i) in liver of smelt than in that of Atlantic
      salmon and capelin (nonglycerol accumulators), (ii) in liver of smelt maintained
      at 1 degrees C than in that of smelt held at 8 degrees -10 degrees C, and (iii)
      in smelt liver than in smelt muscle, heart, brain, or kidney. In addition,
      transcript levels of cGPDH in liver peak in December during the onset of glycerol
      production and then decline over the remainder of the season. There are four
      cGPDH protein isoforms in smelt liver that are present regardless of glycerol
      production status. A minimum of four cGPDH gene copies identified by Southern
      blotting provide adequate genetic potential to yield multiple protein isoforms. A
      full-length cDNA for smelt mitochondrial glycerol-3-phosphate dehydrogenase
      (mGPDH) was cloned and characterized. The 2,790-bp cDNA contains a 109-bp 5'UTR,
      a 2,193-bp open reading frame, and a 488-bp 3'UTR; transcripts are ubiquitously
      expressed in both warm- and cold-acclimated smelt tissues. Smelt mGPDH encodes a
      730-aa protein that clusters with that of zebrafish and frog and contains several
      common structural motifs. mGPDH transcript levels generally increase late in the
      seasonal glycerol cycle, and mGPDH enzyme activity increases significantly during
      the glycerol decrease phase. Taken together, these findings suggest that liver
      cGPDH and mGPDH play a key role in the glycerol accumulation and decrease phases,
      respectively.

PMID- 21743251
TI  - Within-species digestive tract flexibility in rufous-collared sparrows and the
      climatic variability hypothesis.
AB  - The climatic variability hypothesis (CVH) states that species are geographically
      more widespread at higher latitudes because individuals have a broader range of
      physiological tolerance or phenotypic flexibility as latitude and climatic
      variability increase. However, it remains unclear to what extent climatic
      variability or latitude, acting on the phenotype, account for any observed
      geographical gradient in mean range size. In this study, we analyzed the
      physiological flexibility within the CVH framework by using an intraspecific
      population experimental approach. We tested for a positive relationship between
      digestive-tract flexibility (i.e., morphology and enzyme activities) and latitude
      and climatic and natural diet variability in populations of rufous-collared
      sparrows (Zonotrichia capensis) captured in desert (27 degrees S), Mediterranean
      (33 degrees S), and cold-temperate (41 degrees S) sites in Chile. In accordance
      with the CVH, we observed a positive relationship between the magnitude of
      digestive-tract flexibility and environmental variability but not latitude. The
      greatest digestive flexibility was observed in birds at middle latitudes, which
      experience the most environmental variability (a Mediterranean climate), whereas
      individuals from the most stable climates (desert and cold-temperate) exhibited
      little or no digestive-tract flexibility in response to experimental diets. Our
      findings support the idea that latitudinal gradients in geographical ranges may
      be strongly affected by the action of regional features, which makes it difficult
      to find general patterns in the distribution of species.

PMID- 21743252
TI  - The effects of low-speed swimming following exhaustive exercise on metabolic
      recovery and swimming performance in brook trout (Salvelinus fontinalis).
AB  - Experiments were conducted to determine whether low-speed swimming during
      recovery from exhaustive exercise improved both metabolic recovery and
      performance during a swimming challenge. For these experiments, brook trout were
      allowed to recover from exhaustive exercise for 2 h while swimming at 0, 0.5,
      1.0, or 1.5 body length (BL) s(-1) or allowed to recover from exhaustive exercise
      for 1, 2, or 3 h while swimming at 1.0 BL s(-1). At the appropriate interval,
      either (i) muscle and blood samples were removed from the fish or (ii) fish were
      assessed for performance (i.e., fatigue time) during a fixed-interval swimming
      test. Low-speed swimming during recovery from exhaustive exercise resulted in
      significantly longer fatigue times compared with fish recovering in still water
      (i.e., 0 BL s(-1)). However, swimming during recovery did not expedite recovery
      of muscle lactate or blood variables (e.g., lactate, osmolarity, glucose). These
      observations suggest that metabolic recovery and subsequent swimming performance
      may not be directly linked and that other factors play a role in swimming
      recovery in brook trout.

PMID- 21743253
TI  - Effects of training and testosterone on muscle fiber types and locomotor
      performance in male six-lined racerunners (Aspidoscelis sexlineata).
AB  - Testosterone (T) is thought to affect a variety of traits important for fitness,
      including coloration, the size of sexual ornaments, aggression, and locomotor
      performance. Here, we investigated the effects of experimentally elevated T and
      locomotor training on muscle physiology and running performance in a
      nonterritorial male lizard species (Aspidoscelis sexlineata). Additionally,
      several morphological attributes were quantified to examine other characters that
      are likely affected by T and/or a training regimen. Neither training alone nor
      training with T supplementation resulted in increased locomotor performance.
      Instead, we found that T and training resulted in a decrease in each of three
      locomotor performance variables as well as in hematocrit, ventral coloration, and
      testis size. Strikingly, neither the size nor the fiber composition of the
      iliofibularis or gastrocnemius muscles was different among the two treatments or
      a group of untrained control animals. Hence, the relationships among T, training,
      and associated characters are not clear. Our results offer important insights for
      those hoping to conduct laboratory manipulations on nonmodel organisms and
      highlight the challenges of studying both training effects and the effects of
      steroid hormones on locomotor performance.

PMID- 21743254
TI  - Experimental tests of endocrine function in breeding and nonbreeding raptors.
AB  - Many long-lived avian species defer reproduction for several years, often
      displaying a "floating" behavior characterized by the lack of mates and exclusive
      territories. Understanding the proximate mechanisms regulating floating behavior
      is a relevant topic of research for physiologists, behavioral ecologists, and
      population biologists because a prolonged period of nonbreeding can negatively
      affect lifetime fitness and change population dynamics. Here we tested two
      hypotheses linking endocrine function to floating status: (a) floaters undergo a
      period of sexual immaturity characterized by lower gonadal function (hypothesis
      of sexual immaturity), and (b) floating status is socially imposed by dominant
      conspecifics and revealed by the adrenocortical response to stress (hypothesis of
      social subordination). The two hypotheses were tested in a population of free
      living black kites Milvus migrans in Donana National Park (southwest Spain),
      where breeders coexist with young floaters that defer reproduction for 3-7 yr.
      Hypophysial-gonadal function, estimated as androgen production in response to
      experimental challenge with gonadotropin-releasing hormone (c-GnRH-I), was
      similar in magnitude and timing between floating and breeding males. The same
      treatment was, however, unable to elicit any response in terms of increasing
      estradiol or total androgen levels in females regardless of their breeding
      status. Following experimental capture and restraint, the adrenocortical response
      to stress (estimated as circulating corticosterone levels) was higher in floating
      than in breeding males, while females showed the opposite pattern (i.e., lower
      response to stress in young floaters compared with breeders). Contrary to the
      hypothesis of sexual immaturity, our results suggest that floating males are
      physiologically capable of reproducing. The reported differences in
      adrenocortical function support the idea that floaters are socially subordinate
      to breeders, and corticosterone responses reflect the sex-specific roles during
      competition in socially monogamous species.

PMID- 21743255
TI  - Coping with intense reproductive aggression in male arctic ground squirrels: the
      stress axis and its signature tell divergent stories.
AB  - We tested the adaptive stress hypothesis that male arctic ground squirrels
      (Urocitellus parryii) exhibit a stress response over the course of the breeding
      season that is characterized by increasing free cortisol concentrations,
      increasing mobilization of stored energy, and decreasing physical condition. We
      assessed the functioning of the hypothalamic-pituitary-adrenal axis by measuring
      cortisol levels in response to the stress of capture and in response to a hormone
      challenge protocol (dexamethasone suppression and adrenocorticotropic hormone
      stimulation). We measured blood glucose levels, free fatty acids, white blood
      cells, and hematocrit to assess the downstream physiological responses to
      cortisol. Immediately after spring emergence, male arctic ground squirrels had
      ample free abdominal fat and few signs of wounding. By the end of the breeding
      season 3 wk later, visible fat reserves were almost entirely gone, and most males
      had extensive wounds. Total plasma cortisol concentrations increased over this
      period, but so did corticosteroid-binding capacity, resulting in no change in the
      free cortisol response to capture. We found no significant changes in how the
      animals responded to our hormone challenges, contrary to our prediction that the
      stress axis should increase free cortisol production. Even though we found no
      change in the functioning of the stress axis, all of the downstream measures
      suggested that male arctic ground squirrels are chronically exposed to high
      cortisol concentrations. Over the breeding season, blood glucose increased, fat
      stores and circulating free fatty acids were depleted, and both hematocrit levels
      and white blood cell counts decreased significantly. Our data suggest that a more
      complex relationship between the stress axis and downstream measures of stress
      exists than that proposed by the adaptive stress hypothesis. We propose several
      nonexclusive, testable mechanisms that could explain our observations.

PMID- 21743256
TI  - Effects of sibling competition on growth, oxidative stress, and humoral immunity:
      a two-year brood-size manipulation.
AB  - We investigated the effects of ecological context (by comparing data from two
      consecutive years) and experimentally manipulated nestling developmental
      conditions (large vs. small brood size) on immune function (immunoglobulin Y
      [IgY]) and oxidative stress in nestling European starlings Sturnus vulgaris. On
      the basis of annual differences in chicks' morphological traits and body masses
      close to fledging, we established that 2007 was a relative low-quality year and
      2008 was a relatively high-quality year. Total antioxidant capacity (TAC) was
      significantly lower in experimentally enlarged broods, but only in the low
      quality year (2007). Total oxidant status (TOS) was independent of brood size in
      both years but was 45% higher in the low-quality year. Consequently, plasma
      oxidative status (the ratio between TOS and TAC) was higher in 2007. In contrast,
      plasma IgY levels were higher in the experimentally enlarged broods and in the
      high-quality year (2008). Thus, immune function and oxidative stress showed
      inverse relationships with developmental conditions and annual variation in year
      quality. Finally, TOS and TAC were positively correlated, but only in the low
      quality year (2007), and there was no relationship observed between IgY and
      markers of oxidative stress. Our results demonstrate the importance of taking
      into account year effects or ecological context when assessing environmental
      effects on physiological mechanisms underlying the life-history traits of chicks,
      such as oxidative stress.

PMID- 21743257
TI  - Remodeling mitochondrial membranes during arousal from hibernation.
AB  - During arousal from hibernation, body temperature (T(b)) increases by ~30 degrees
      C and liver mitochondrial respiration increases threefold in as little as 2 h. We
      analyzed liver mitochondria purified from ground squirrels (Ictidomys
      tridecemlineatus) to see whether membrane phospholipids were remodeled during
      spontaneous arousal. Cardiolipin content did not change among animals in torpor
      (T ~ 5 degrees C), the early phase of arousal (T ~ 15 degrees C), late arousal (T
      ~ 30 degrees C), interbout euthermia (T ~ 37 degrees C), and summer-active
      animals (T ~ 37 degrees C) that do not hibernate. Phosphatidylcholine content
      increased in late arousal relative to interbout euthermia, while
      phosphatidylethanolamine decreased. Phospholipid monounsaturated fatty acids
      (MUFAs) did not change throughout arousal, but polyunsaturated fatty acids
      (PUFAs) and MUFA/PUFA decreased and increased, respectively. In the fatty acid
      conjugates of phospholipids, neither unsaturation index nor n-3/n-6 differed. Few
      changes in individual fatty acids were noted, but palmitoleic acid (16:1, n-7)
      was higher in interbout euthermia and summer. Although 16:1 accounted for less
      than 1.5% of phospholipid fatty acids, it correlated strongly and positively with
      succinate-fueled state 3 mitochondrial respiration. No other phospholipid
      characteristic measured here correlated with mitochondrial respiration. These
      data show that mitochondrial membranes are remodeled rapidly during arousal, but
      the contribution to reversible suppression of mitochondrial respiration remains
      unclear.

PMID- 21743258
TI  - Impact of a mass media campaign to increase public awareness of hypertension.
AB  - OBJECTIVES: We evaluated the effect of a nationwide media campaign on
      hypertension awareness in the population, which was implemented with the aim of
      spreading key messages related to optimal blood pressure levels and encouraging
      blood pressure measurements. STUDY DESIGN: A nationwide project called "12/8
      Awareness Campaign" was implemented between October 2005 and January 2006 using
      all available mass and outdoor media aiming to improve the knowledge of people on
      normal blood pressure values and to encourage regular blood pressure
      measurements. Four survey questions to inquire the level of awareness related to
      optimal blood pressure levels, hypertension, and hypertension-related disease
      conditions were directed via face-to-face interviews to two separate samples
      representing the general Turkish population before (n=1716) and after (n=1725)
      the campaign, respectively. The answers of the pre- and post-campaign individuals
      were compared. RESULTS: After the campaign, the percentage of participants who
      did not know their blood pressure levels decreased from 54.8% to 47.8%, the
      percentage of those who checked their blood pressure within the past two months
      increased from 34.3% to 39.6%, and the percentage of those who were aware of the
      optimal blood pressure levels rose from 51.8% to 58.6% (p<0.001). CONCLUSION: The
      campaign contributed significantly to the awareness of hypertension in general
      population, which is highly encouraging for future efforts for early detection of
      hypertension and prevention of related morbidity and mortality.

PMID- 21743259
TI  - Inappropriate use of digoxin in elderly patients presenting to an outpatient
      cardiology clinic of a tertiary hospital in Turkey.
AB  - OBJECTIVES: We investigated the prevalence and indications of digoxin use in
      elderly patients presenting to a cardiology outpatient clinic of a tertiary
      hospital in Turkey. STUDY DESIGN: On a prospective basis, the study included 800
      consecutive patients aged 70 or over (mean age 77 +/- 6 years) who presented to
      our cardiology outpatient clinic. There were 124 patients (15.5%) receiving
      digoxin. All the patients underwent transthoracic echocardiography. Digoxin use
      was considered inappropriate if the patient had normal left ventricle systolic
      function or if there was no atrial fibrillation (AF). RESULTS: The reasons for
      use of long-term digoxin were persistent AF (n=55, 44.4%), heart failure (HF)
      (n=51, 41.1%), and paroxysmal AF (n=8, 6.5%). The exact reason could not be
      determined in 10 patients (8.1%). Digoxin use was based on appropriate
      indications in 76 patients (61.3%), whereas 48 patients (38.7%) were taking
      digoxin with inappropriate indications. Of 51 patients for whom HF was the only
      reason for digoxin therapy, diagnosis of HF was incorrect in 30 patients (24.2%).
      Other inappropriate indications were paroxysmal AF and undetermined indication
      for digoxin prescription. Concerning digoxin dose, 24 patients (19.4%) received
      one tablet (0.25 mg) and 30 patients (24.2%) received a half tablet (0.125 mg) on
      a daily basis, while 10 patients (8.1%) used six tablets per week with one day
      off (0.214 mg/day) and 60 patients (48.4%) took five tablets per week with two
      days off (0.179 mg/day). The median daily dose was 0.182 mg/day. Digoxin dose was
      higher than the recommended doses for elderly patients in 75.8% of the patients.
      CONCLUSION: Our findings show that nearly 40% of elderly patients receive digoxin
      with inappropriate indications and 75% of these patients take digoxin at higher
      doses than the recommended doses for this age group.

PMID- 21743260
TI  - The relationship between paraoxonase-1 activity and coronary artery disease in
      patients with metabolic syndrome.
AB  - OBJECTIVES: We investigated the correlation of serum paraoxonase-1 (PON-1)
      activity with coronary artery disease (CAD) in patients with metabolic syndrome
      (MetS). STUDY DESIGN: The study included 21 patients (mean age 55 +/- 9 years)
      with MetS, stable angina pectoris, and angiographically shown CAD, 24 patients
      (mean age 51 +/- 10 years) with MetS and angiographically normal coroner
      arteries, and 28 healthy controls (mean age 49 +/- 12 years). Demographic and
      clinical characteristics, insulin levels, homeostasis model assessment of insulin
      resistance index, and PON-1 activity were assessed in all the groups. Severity of
      CAD was assessed using the Gensini score. RESULTS: Paraoxonase-1 activity was
      significantly lower in patients with MetS compared to the control group (p=0.02).
      The two MetS groups with and without CAD exhibited similar characteristics in all
      the parameters including PON-1 activity (p>0.05). Univariate correlation analysis
      performed in MetS-CAD patients showed a significant negative correlation between
      the Gensini score and PON-1 activity (r=-0.48, p=0.02). The overall PON-1
      activity of all the subjects showed no correlation with the parameters examined.
      CONCLUSION: Decreased PON-1 activity in patients with MetS compared to the
      control group suggests increased oxidative stress in MetS. Detection of similar
      PON-1 activity levels in MetS groups with and without CAD suggests that
      disturbance of oxidative-antioxidative balance occurs before the development of
      CAD. The negative correlation between the Gensini score and PON-1 activity
      implies that decreased PON-1 activity may be one of the etiologic causes of
      atherosclerotic progress in MetS.

PMID- 21743261
TI  - [Assessment of regional left ventricular functions by strain and strain rate
      echocardiography in type II diabetes mellitus patients without microvascular
      complications].
AB  - OBJECTIVES: We evaluated regional left ventricular myocardial functions by strain
      (S) and strain rate (Sr) echocardiography in patients with type II diabetes
      mellitus (DM) without microvascular complications. STUDY DESIGN: The study
      included 40 DM patients (20 women, 20 men; mean age 52.4 +/- 7.9 years) without
      microvascular complications, and 40 healthy controls (20 women, 20 men; mean age
      52.8 +/- 10.1 years). Left ventricular functions were evaluated by conventional
      Doppler, tissue Doppler, and S-Sr echocardiography. Longitudinal peak systolic S
      and Sr were measured from the basal, mid and apical segments of the left
      ventricle walls. Patients with DM duration of >3 years (n=24) and receiving
      medical therapy for DM (n=30) were also evaluated. RESULTS: Conventional Doppler
      findings were similar in the patient and control groups. Among tissue Doppler
      variables, only early diastolic mitral annular velocity (Em) was significantly
      decreased (10 +/- 2.9 vs. 11.4 +/- 3.2 cm/sec, p<0.05), and accordingly, mitral
      inflow E/Em ratio was significantly increased (7.3 +/- 2.5 vs. 6.3 +/- 2, p<0.05)
      in patients with DM. The two groups were similar with respect to systolic S and
      Sr values, except for apical-lateral S, mid-anterior S, basal-anteroseptal S,
      apical-anterior Sr, and mid-anteroseptal Sr (p<0.05, for all). Patients with DM
      duration of >3 years and receiving medical therapy showed similar changes as the
      overall patient group. CONCLUSION: The frequency of left ventricular diastolic
      dysfunction was higher in patients with DM. Irregular distribution of systolic S
      and Sr indices in the left ventricular segments may indicate that DM leads to
      heterogeneous myocardial involvement also in the early period.

PMID- 21743262
TI  - [Percutaneous closure of interatrial septal defects: mid-term follow-up results].
AB  - OBJECTIVES: We evaluated short- and mid-term results of percutaneous closure of
      atrial septal defects (ASD) and patent foramen ovale (PFO) using various closure
      devices. STUDY DESIGN: The study included 278 patients (128 men, 150 women; mean
      age 39+/-12 years; range 17 to 66 years) who underwent percutaneous closure of
      secundum ASD (n=134) or PFO (n=144). All the patients were assessed by
      transthoracic (TTE) and transesophageal (TEE) echocardiography before the
      procedure. Percutaneous closure was performed with the Amplatzer (n=180),
      Occlutech Figulla (n=92) or BioSTAR (n=6) devices. Closure of ASDs was performed
      under general anesthesia with TEE guidance, and closure of PFOs was performed
      under local anesthesia with TTE guidance. Follow-up controls were at 1, 6, and 12
      months, and annually thereafter. The mean follow-up period was 35.1 +/- 24.6
      months for ASD cases, and 24.9 +/- 15.5 months for PFO cases. RESULTS: The mean
      device size was 20.2 +/- 5.6 mm for ASD cases and 24 +/- 2.9 mm for PFO cases.
      The mean procedural and fluoroscopy times were 28.4 +/- 6.1 min and 4.9 +/- 2.1
      min for ASD closure, and 18.2 +/- 5.3 min and 3.6 +/- 1.2 min for PFO closure,
      respectively. Procedural device embolization occurred in only one patient. No
      recurrent embolic events occurred after PFO closure, and no residual shunts were
      seen after ASD closure. Device thrombosis developed in two patients during the
      procedure and in one patient at one-year follow-up. CONCLUSION: Percutaneous
      closure of secundum ASDs and PFOs using the Amplatzer, Occlutech Figulla, and
      BioSTAR devices is an effective and safe treatment option.

PMID- 21743263
TI  - [Comparison of psychosocial risk factors between patients who experience acute
      myocardial infarction before and after 40 years of age].
AB  - OBJECTIVES: Several studies have shown that psychosocial risk factors such as
      stress and depression make substantial contribution to the pathogenesis of
      coronary artery disease. This study aimed to investigate acute stress factors
      prior to acute myocardial infarction (AMI), and stress, depression, and anxiety
      levels during the subacute period in AMI patients aged <= 40 years, in comparison
      with AMI patients aged >40 years. STUDY DESIGN: The study included 200 first-time
      AMI patients aged <= 40 years (n=100; mean age 35 +/- 4 years) and >40 years
      (n=100; mean age 54 +/- 9 years). The DASS 21 scale (Depression Anxiety Stress
      Scales) was administered via face-to-face interviews in the early recovery period
      of AMI. The patients were also questioned whether they had experienced acute
      stress factors such as severe emotional or physical stressful events within two
      hours before the onset of chest pain. In addition, coronary angiography results
      were assessed based on the two age groups. RESULTS: Comparison of the two age
      groups showed significantly higher frequencies of family history of CAD and
      smoking in the younger group, and significantly higher frequencies of
      hypertension, diabetes mellitus, and dyslipidemia in the older group (p<0.05).
      History of acute stress factors was significantly more common (52% vs. 20%,
      p<0.01) and stress, depression, and anxiety scores of the DASS 21 scale were all
      significantly higher in the younger group (p<0.01). On coronary angiography,
      younger patients predominantly had normal coronary arteries and single-vessel
      disease, whereas multi-vessel disease was more prevalent in the older age group
      (p<0.01). CONCLUSION: Triggers of acute stress and psychosocial risk factors may
      contribute to the occurrence of AMI in individuals younger than 40 years.

PMID- 21743264
TI  - [Extraction of a large vegetation and ICD lead using the Evolution Mechanical
      Dilator Sheath].
AB  - A 74-year-old male patient presented with complaints of fatigue, fever, and
      worsening health status. He had a 34-month history of cardioverter-defibrillator
      (ICD) implantation due to ischemic cardiomyopathy. Transthoracic and
      transesophageal echocardiography showed a mobile mass, 24 x 11 mm in size,
      consistent with a vegetation attached to the right ventricular ICD lead. Surgical
      removal of the electrode was considered to be highly risky for the patient, thus
      percutaneous removal was decided. Due to adhesions, manual traction of the lead
      with a standard stylet was ineffective. Complete lead extraction was accomplished
      using the Evolution Mechanical Dilator Sheath, which is a new mechanical sheath
      with a stainless steel bladed tip. No complications occurred during or after the
      procedure. Following a histopathologic diagnosis of vegetation, the patient
      received a six-week antibiotic therapy, after which a new ICD was implanted on
      the contralateral side. To our knowledge, this case represents the largest lead
      vegetation extracted by this new device. Although its safety should be validated
      by increasing number of cases, it seems that its simple use would make this
      device a new interesting tool among the instruments available for lead
      extraction.

PMID- 21743265
TI  - [Pericardial tamponade associated with Epstein-Barr virus in an immunocompetent
      young patient].
AB  - Acute pericarditis may result from many etiologies. Pericarditis as a
      complication of Epstein-Barr virus (EBV) infection is quite rare and is usually
      self-limited in immunocompetent patients. In particular, pericardial tamponade
      associated with EBV infection has been reported in only one case. An 18-year-old
      woman presented with chest pain and shortness of breath. Upon suspicion of
      pulmonary embolism, the patient was examined with computed tomography, which
      showed no pulmonary embolism, but massive pericardial fluid surrounding the whole
      pericardium. Transthoracic echocardiography revealed pericardial fluid
      collections in the posterolateral wall (3.5 cm), right ventricle (2 cm), and
      right atrium (1.4 cm), and a diastolic collapse of the right ventricular apical
      wall. Emergency pericardiocentesis was performed and a total of 750 ml fluid was
      removed, which resulted in hemodynamic improvement and disappearance of the
      diastolic collapse on echocardiography. Serum EBV VCA IgM and EBV PCR assays were
      found positive and medical therapy was instituted with the diagnosis of EBV
      associated pericarditis. The patient showed complete improvement and was
      discharged. At one-month control, she was free of symptoms and her echocardiogram
      was normal.

PMID- 21743266
TI  - [Massive pulmonary thromboembolism after abdominoplasty and liposuction].
AB  - Pulmonary embolism is a rare complication of abdominoplasty and liposuction that
      may result in a fatal consequence. A 65-year-old obese woman presented with
      complaints of shortness of breath, palpitation, and hypotension (90/60 mmHg)
      seven weeks after abdominoplasty and liposuction. The electrocardiogram showed
      sinus tachycardia, right axis deviation, and right bundle branch block. The chest
      X-ray showed atelectatic and focally infiltrated areas, and minimal bilateral
      pleural effusion. Laboratory findings were normal except for D-dimer level (3500
      ng/ml). Echocardiography revealed dilated right heart chambers and a thrombus in
      the left ventricle. Ejection fraction was normal and pulmonary artery pressure
      was 50 mmHg. Doppler ultrasound showed no signs of thrombosis. Following the
      diagnosis of pulmonary thromboembolism, the patient received oxygen therapy and
      heparin infusion. However, the clinical course did not improve, hemodynamic
      deterioration continued, and the echocardiographic appearance of the thrombus
      persisted, so thrombolytic therapy with tissue plasminogen activator was
      administered, which also resulted in no response. In the end, pulmonary
      embolectomy was performed and the thrombus was successfully extracted. The
      patient had an uneventful postoperative course and was discharged on the seventh
      postoperative day.

PMID- 21743267
TI  - [Primary coronary intervention for acute ST-elevation myocardial infarction in a
      patient with immune thrombocytopenic purpura].
AB  - The ideal treatment for acute myocardial infarction in patients with idiopathic
      thrombocytopenic purpura (ITP) is not well-known. A 42-year-old male patient with
      a previous diagnosis of chronic and refractory ITP was admitted with chest pain
      of four-hour onset. Findings of electrocardiography was consistent with acute
      anteroseptal myocardial infarction. He had no risk factors for coronary heart
      disease and was not receiving treatment for ITP, and his platelet count varied
      between 11,000 and 40,000/ul before presentation, without any event of bleeding.
      Transthoracic echocardiography showed hypokinesia of the anterior, middle, and
      apical segments. Cardiac enzyme levels were elevated and platelet count was
      41,000/ul. Coronary angiography revealed total occlusion of the left anterior
      descending artery. Primary percutaneous coronary intervention (PCI) was
      performed, which included predilation and stenting of the lesion. There were no
      bleeding or ischemic complications during or after PCI and the patient was
      discharged on the fifth day without any symptoms. He was instructed to take 75 mg
      clopidogrel daily for two weeks. He was symptom-free at a control visit after
      this period, with normal left ventricular wall motion on echocardiography.

PMID- 21743268
TI  - Dislodgement of a sirolimus-eluting stent in the circumflex artery and its
      successful deployment with a small-balloon technique.
AB  - Coronary stent dislodgement or embolization before deployment is a rare but
      serious complication in interventional cardiology. A 60-year-old male presented
      with unstable angina five years after coronary artery bypass surgery. There was a
      stenosis (70%) in the obtuse marginal branch of the circumflex artery. During
      percutaneous coronary intervention, a sirolimus-eluting stent was stripped from
      its balloon mainly because of significant proximal angulation and incarcerated
      within the proximal circumflex artery. A smaller balloon dilatation catheter was
      advanced and pushed through the inside of the slipped stent. Using this
      technique, the stent could be advanced into the lesion and was successfully
      deployed. To our knowledge, this is the first case report on sirolimus-eluting
      stent dislodgement.

PMID- 21743269
TI  - Atrial septal stenting to increase interatrial shunting in cyanotic congenital
      heart diseases: a report of two cases.
AB  - Aiming to increase mixing at the atrial level, atrial septal stenting was
      performed in two pediatric cases with cyanotic congenital cardiac diseases. The
      first case was a 3-month-old male infant with transposition of the great
      arteries. The second case was an 18-month-old male infant with increased central
      venous pressure due to postoperative right ventricular outflow tract obstruction.
      Premounted bare stents of 8 mm in diameter were used in both cases. The length of
      the stent was 20 mm in the first case and 30 mm in the latter. The procedure was
      accomplished without any complications. In the first case, oxygen saturation
      increased approximately 20-25% with no significant interatrial gradient. In the
      latter, central venous pressure decreased from 16 to 8 mmHg immediately after the
      procedure. The patient was weaned from the ventilator on the second day and
      discharged from intensive care unit on the fifth day. Follow-up echocardiograms
      of both patients showed patent stents with good position relative to the atrial
      septum. Stenting of the atrial septum seems to be a safe and effective method to
      create a reliable, nonrestrictive interatrial communication.

PMID- 21743270
TI  - Very early management of acute heart failure syndromes.
AB  - Diagnosis and management of acute heart failure syndromes are described in the
      most recent ESC/ESICM guidelines. However, physicians dealing with these patients
      in their daily practice may need guidance in choosing therapeutic alternatives as
      soon as the dyspneic patient arrives to the emergency department. Herein,
      practical recommendations for the very early management of patients with acute
      heart failure syndromes are presented. Blood pressure- and symptom-driven
      strategy along with early initiation of goal-directed therapies are key take-home
      messages. Furthermore, early and frequent reassessment is also an imperative part
      of management so that adjustments in the initial therapeutic plan can be achieved
      in a timely fashion.

PMID- 21743271
TI  - [Suggestions on how to do: practical tips for the measurement of fractional flow
      reserve (FFR)].

PMID- 21743272
TI  - A rare complication of thromboembolism: entrapped thrombus in a patent foramen
      ovale.

PMID- 21743273
TI  - Iatrogenic huge renal arteriovenous fistula.

PMID- 21743274
TI  - Coronary artery fistula presenting as a left atrial mass.

PMID- 21743275
TI  - Coil embolization of a primary aortobronchial fistula.

PMID- 21743276
TI  - Electrocardiographic artifact during exercise.

PMID- 21743278
TI  - Inhibitory effect of receptor for advanced glycation end products (RAGE) on the
      TGF-beta-induced alveolar epithelial to mesenchymal transition.
AB  - Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease
      characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs)
      are thought to produce myofibroblasts through the epithelial to mesenchymal
      transition (EMT). Receptor for advanced glycation end products (RAGE) is a member
      of the immunoglobulin superfamily of cell surface receptors whose activation is
      associated with renal fibrosis during diabetes and liver fibrosis. RAGE is
      expressed at low basal levels in most adult tissues except the lung. In this
      study, we evaluated the interaction of ligand advanced glycation end products
      (AGE) with RAGE during the epithelial to myofibroblast transition in rat AECs.
      Our results indicate that AGE inhibited the TGF-beta-dependent alveolar EMT by
      increasing Smad7 expression, and that the effect was abolished by RAGE siRNA
      treatment. Thus, the induction of Smad7 by the AGE-RAGE interaction limits the
      development of pulmonary fibrosis by inhibiting TGF-beta-dependent signaling in
      AECs.

PMID- 21743279
TI  - [Clinical experience of 52 patients undergoing laparoscopic radical
      prostatectomy].
AB  - Perioperative results and oncological and functional results were evaluated for
      52 patients who underwent laparoscopic radical prostatectomy (LRP). Median
      operative time was 341 minutes and median blood loss was 828 ml. The
      intraoperative complications were hemorrhage exceeding 3,000 ml (five cases),
      ureteral injury (two cases), and rectal injury (one case). The median day of
      catheter removal was postoperative day 7. Postoperative complications were
      temporal arrhythmia, mild hydronephrosis, port site hernia, urethral stricture,
      and a giant lymphocele. When surgical results were compared between the firsthalf
      cases and second-half cases who were operated on by a single surgeon, median
      operative time and intraoperative hemorrhage did not differ significantly between
      the two halves but the day of catheter removal after LRP was significantly
      earlier for the second-half group. The pathological stage was pT3 in 41.2% of the
      patients and the negative surgical margin rate was 62.7%. The 3-year PSA-failure
      free survival rate was 64. 1%. Pad-free status (0-1 pad/day) was achieved in
      84.4% of the patients. Erectile function was preserved in 58.3% of patients
      undergoing nerve-sparing LRP. Although the complication rate and the quality of
      operative procedures gradually improved, efforts to improve the oncological and
      functional outcomes of LRP must continue.

PMID- 21743280
TI  - [Complete response of lung metastasis to interferon-alpha therapy after radical
      nephrectomy for sarcomatoid renal cell carcinoma with Stauffer syndrome: a case
      report].
AB  - A 75-year-old man was admitted to our hospital with liver dysfunction and
      elevated C-reactive protein level. He was diagnosed with renal tumor by
      ultrasonography. Computed tomography revealed a renal cell carcinoma (cT3aN0M0)
      with Stauffer syndrome. Laparoscopic radical nephrectomy was performed.
      Histological findings indicated clear cell carcinoma with a sarcomatoid
      component. After 1 month, lung metastasis was detected on an X-ray film.
      Interferon-alpha was administered, and complete response was achieved 2 months
      later. He has shown no evidence of recurrence in 27 months.

PMID- 21743281
TI  - [Successful interferon-alpha therapy of renal cell carcinoma with lung
      metastasis: a case report].
AB  - A 67-year-old man was admitted with a chief complaint of dyspnea. Computed
      tomography (CT) revealed a left renal tumor, 12 cm in diameter, with tumor
      thrombus in the left renal vein, multiple lung metastases, right pleural
      effusion, and para-aortic lymph node metastases. Because of poor condition in
      respiratory status, nephrectomy was considered to be impossible and the patient
      was administered 6*106 IU of interferon-alpha daily. Then, 6*106 IU was also
      administered three times a week. At 14 months after interferon-alpha therapy, CT
      scan showed complete remission of lung, pleura metastases and right pleural
      effusion, and the left renal tumor was markedly reduced in size. Because of
      improvement of general condition, nephrectomy of the left kidney was performed.
      Twenty-seven months after the start of interferon-alpha therapy, the patient is
      alive without evidence of disease.

PMID- 21743282
TI  - [Hemodialysis case in which RCC was identified after disappearance of perirenal
      hematoma following spontaneous renal rupture treated by transcatheter arterial
      embolization].
AB  - A 55-year-old man who had been undergoing hemodialysis for 9 years visited our
      institution after the sudden onset of severe left flank pain. He presented with
      hypotension and was admitted immediately because computed tomography (CT)
      revealed a massive perirenal hematoma. Renal arteriography showed contrast media
      leakage at the lower branch of the left renal artery, and spontaneous renal
      rupture was diagnosed. Five months after the bleeding was stopped by selective
      transcatheter embolization of the branch of renal artery, CT showed an enhanced
      mass at the upper pole of left kidney and renal cell carcinoma (RCC) was
      suspected. Radical nephrectomy was performed, the pathological diagnosis was
      clear cell carcinoma, and the man has not experienced recurrence within 36 months
      after the surgery. RCC did not appear to be the cause of the original hemorrhage
      because there was a small residual hematoma in the middle of the renal parenchyma
      that was separated from the RCC. In cases of spontaneous renal rupture, re
      evaluation by imaging studies is mandatory after disappearance of perirenal
      hematoma because imaging studies at the time of the rupture sometimes do not
      reveal the cause of the hemorrhage.

PMID- 21743283
TI  - [Ureteral cancer found in megaureter].
AB  - A 74-year-old female consulted our hospital for follow up of bilateral
      megaureter. She requested continued follow-up, but in February 2009, she had
      gross hematuria. We could not make a diagnosis by drip infusion pyelography and
      retropyelography, so enhanced computed tomography (CT) and magnetic resonance
      urography were performed. They revealed right ureteral cancer with severe
      megaureter. Right nephroureterectomy and partial cystectomy was performed in
      August 2009. The pathological findings were urothelial carcinoma. She did not
      receive adjuvant chemotherapy and has had no recurrence for 6 months.

PMID- 21743284
TI  - [A case of primary urothelial carcinoma of the prostate responsive to MVAC intra
      arterial chemotherapy: a case report].
AB  - A 70-year-old man visited a urological clinic on May 2008 complaining of dysuria
      and nocturia since 2 years prior. He was diagnosed as having gross benign
      prostatic hypertrophy, and was referred to a nearby hospital for transurethral
      resection of prostate (TURP). During TURP, a papillary tumor was found in the
      prostatic urethra on the left side and a biopsy was performed. A pathological
      examination revealed urothelial carcinoma G3. Cystoprostatectomy was planned, but
      the patient refused the procedure. Therefore, he underwent three courses of MVAC
      intra-arterial chemotherapy (methotrexate, vinblastin, doxorubicin, cisplatinum)
      at our hospital. After chemotherapy, no tumor was found in the prostatic urethra
      and a pathological report of repeat TUR showed no tumor. Currently, the patient
      is alive and there has been no evidence of recurrence for 1 year and 10 month.

PMID- 21743285
TI  - [A case of ductal adenocarcinoma of the prostate treated with endocrine therapy
      and radiation therapy].
AB  - We report a case of ductal adenocarcinoma of the prostate. A 81-year-old man
      presented with a complaint of microhematuria. Serum prostate specific antigen
      (PSA) was 18. 44 ng/ml. A cystourethroscopic examination revealed a papillary
      tumor near the verumontanum. Transurethral resection of the tumor and transrectal
      prostatic needle biopsy was carried out. The pathological diagnosis was ductal
      adenocarcinoma and acinar adenocarcinoma of the prostate. The tumor responded to
      endocrine therapy and radiation therapy. At the follow up at 18 months, the PSA
      level was in the undetectable range (<0.01 ng/ml), and no reccurence of the tumor
      was seen. Pathogenesis and management of this rare condition is discussed.

PMID- 21743286
TI  - The weaker sex.

PMID- 21743287
TI  - Osteoporosis and risk of fracture in patients with diabetes: an update.
AB  - Diabetes mellitus (DM) and osteoporotic fractures are two of the most important
      causes of mortality and morbidity in older subjects. Recent data report a close
      association between fragility fracture risk and DM of both type 1 (DM1) and type
      2 (DM2). However, DM1 is associated with reduced bone mineral density (BMD),
      whereas patients with DM2 generally have normal or increased BMD. This apparent
      paradox may be explained by the fact that, at a given level of BMD, diabetic
      patients present lower bone quality with respect to non-diabetics, as shown by
      several studies reporting that diabetes may affect bone tissue by means of
      various mechanisms, including hyperinsulinemia, deposition of advanced
      glycosylation endproducts (AGEs) in collagen, reduced serum levels of IGF-1,
      hypercalciuria, renal failure, microangiopathy and inflammation. In addition, the
      propensity to fall and several comorbidities may further explain the higher
      fracture incidence in DM patients with respect to the general population. It is
      reasonable to expect that close metabolic control of diabetes may improve bone
      status, although its effect on reduction of fracture risk has not yet been
      demonstrated. However, metformin has a direct effect on bone tissue by reducing
      AGE accumulation, whereas insulin acts directly on osteoclast activity, and
      thiazolidinediones (TZD) may have a negative effect by switching mesenchymal
      progenitor cells to adipose rather than bone tissue. New prospects include the
      incretins, a class of antidiabetic drugs which may play a role linking nutrition
      and bone metabolism. Better knowledge on how diabetes and its treatments
      influence bone tissue may lie at the basis of effective prevention of bone
      fracture in diabetic patients. Thus, close glycemic control, adequate intake of
      calcium and vitamin D, screening for low BMD, and prevention and treatment of
      diabetic complications are key elements in the management of osteoporosis in both
      DM1 and DM2. Attention should be paid to treating diabetes with TZD in women with
      DM2, particularly if elderly. Lastly, patients with osteoporosis and diabetes
      should be offered the same pharmacological treatments as non-diabetics, although
      specific trials on the effects of anti-osteoporotic drugs in the diabetic
      population are lacking.

PMID- 21743288
TI  - Gender differences in associations between ADL and other health indicators in
      1992 and 2002.
AB  - BACKGROUND AND AIMS: Research has shown increased prevalence rates over time in
      several health indicators in the older population. These increases have not been
      accompanied by corresponding increases in ADL and IADL disability. As disability
      and other health indicators follow different trends, the associations between
      them may change. And, as both health and disability also appear to follow
      different trends for men and women, we can expect gender differences in the
      associations. We examined gender differences in how objective tests of function,
      as well as self-reported health and function indicators, were associated with
      ADL/IADL in 1992 and 2002. METHODS: Data came from the Swedish Panel Study of
      Living Conditions among the Oldest Old (SWEOLD), a nationally representative
      interview survey of persons aged 77+. RESULTS: Compared with men, women had
      significantly higher prevalence rates for most health indicators in both survey
      years, but there were no significant gender differences in ADL/IADL limitations.
      Prevalence rates increased significantly between 1992 and 2002 for all health
      indicators, but not for ADL/IADL. Most of the associations between ADL/IADL and
      other health indicators were stronger for men than for women. The overall pattern
      found was that associations have become weaker for women over time; for men, the
      picture was mixed. CONCLUSIONS: The changing associations between ADL/IADL and
      other health indicators may reflect complex interplay between changes in several
      social and environmental factors, some of which may be modifiable. ADL/IADL
      appear to reflect different dimensions of health and different kinds of needs for
      men and women.

PMID- 21743289
TI  - Differential characteristics of bone quality and bone turnover biochemical
      markers in patients with hip fragility fractures and hip osteoarthritis: results
      of a clinical pilot study.
AB  - BACKGROUND AND AIMS: Bone density and quality alterations worsen the ability of
      osteoporotic bone to support prosthetic implants. The aim of our study was to
      evaluate potential differences in bone quality and bone turnover markers in aged
      individuals undergoing surgery for hip fragility fracture or hip osteoarthritis.
      METHODS: Eighteen subjects with hip fragility fractures (Hip Fracture Group), 35
      subjects with osteoarthritis of the hip (Hip Osteoarthritis Group) and 19
      subjects with normal femoral bone mineral density (Control Group) were evaluated.
      Serum and urinary bone markers were assayed preoperatively in all surgical
      patients, and within 48 hours after fracture in the Hip Fracture, Osteoarthritis
      and Control groups. Histomorphometric analysis was performed on surgical samples.
      RESULTS: A significant alteration in calcium and PTH serum levels with
      hyperparathyroidism was observed in the Hip Fracture Group compared with Hip
      Osteoarthritis and Control Groups. C-Terminal telopeptides of type I-collagen
      (CTx) and tartrate resistant-acid phosphatase (TRAP), markers of bone resorption,
      were increased in the Hip Fracture Group compared with both Osteoarthritis and
      Control Groups (CTx: p<0.0007 and p<0.0039 respectively; TRAP: p<0.002 and
      p<0.0007). All subjects were vitamin D3-deficient, but no differences were found
      among the different groups. In addition, histomorphometric data showed better
      maintained connectivity in the Osteoarthritis Group compared with the Hip
      Fracture Group (p<0.0001). CONCLUSIONS: Our data show significant differences in
      bone turnover markers in patients undergoing hip prosthesis for fragility
      fractures, compared with patients operated for hip osteoarthritis.

PMID- 21743290
TI  - Role of clinical frailty on long-term mortality of elderly subjects with and
      without chronic obstructive pulmonary disease.
AB  - BACKGROUND AND AIMS: Elderly subjects are characterized by a high prevalence of
      chronic obstructive pulmonary disease (COPD) and frailty. This study examined the
      predictive role of frailty on long-term mortality in elderly subjects with and
      without COPD. METHODS: The study assessed mortality after a 12-year follow-up in
      489 subjects with COPD and 799 subjects without COPD, selected in 1992. Frailty
      was assessed according to the Frailty Staging System scores ranging from 1 to 7.
      RESULTS: After 12 years' follow-up, mortality was 48.1% in subjects without and
      60.7% in subjects with COPD (p<0.001). With increasing frailty, mortality
      increased from 41.7% to 75.1% (p for trend <0.01) in subjects without and from
      54.3% to 97.0% in subjects with COPD (p for trend <0.001). Multivariate analysis
      showed that both COPD [hazard ratio (HR)=1.34; 95% confidence interval (95%
      CI)=1.02-1.81; p=0.042] and frailty score (HR=1.69 for each unit of increase; 95%
      CI=1.42- 2.00; p<0.001) were predictive of long-term mortality. The frailty score
      also increased the risk of long-term mortality by 34% in the absence of COPD
      (HR=1.34 for each unit of increase; 95% CI=1.02-1.81; p<0.05) and by 80% in its
      presence (HR=1.80 for each unit of increase; 95% CI=1.28-2.53; p<0.001).
      CONCLUSIONS: Long-term mortality was higher in elderly subjects with than in
      those without COPD. The clinical frailty score also significantly predicted
      mortality in subjects without and, even more, in those with COPD. Thus, clinical
      frailty may be considered a new prognostic factor to identify COPD subjects at
      high risk of mortality.

PMID- 21743291
TI  - Psychomotor speed in a random sample of 7,979 subjects aged 30 years and over.
AB  - BACKGROUND AND AIMS: Slowing of psychomotor speed among older individuals has
      been shown in numerous studies. However, in most cases these studies were based
      on small and selected groups of people and, in some cases, the test procedures
      did not allow separation of decision time and motor components of the overall
      performance. The purpose of the present study was to analyse in a large, randomly
      selected population sample the differences in decision and movement times in
      simple and multiple-choice test conditions. The association of educational
      background with psychomotor speed was also examined. METHODS: Data on psychomotor
      speed were collected from a representative nation- wide sample of the Finnish
      population aged 30 years and over (n=7979) with the help of a computerized device
      in simple and multiple-choice test conditions, with visual stimuli. Background
      information (education) was collected by a structured interview. RESULTS: Results
      showed a systematic and significant decline in both decision time and movement
      time when proceeding from the youngest (30-39-year-olds) to the oldest (80+ yrs)
      age groups. This decline was more pronounced in the multiple-choice test than in
      the simple test. In both test conditions, movement times were shorter in men than
      in women. In the young and middle-aged groups, participants with longer formal
      education were faster than the less educated subjects. CONCLUSIONS: On the basis
      of the large representative random sample of this study, it may be concluded that
      decline in psychomotor speed during aging can already be seen at a quite young
      age. Decline accelerates after the age of about 70. Differences in socio-economic
      background factors, such as education, may modify the differences observed
      between younger and older individuals. These results emphasize the need for the
      separation of decision time and movement time in psychomotor speed tests, when
      differences between age groups as well as between men and women are analysed.

PMID- 21743292
TI  - Relationship between plasma ghrelin, insulin, leptin, interleukin 6, adiponectin,
      testosterone and longevity in the Baltimore Longitudinal Study of Aging.
AB  - BACKGROUND AND AIMS: Caloric restriction (CR) is the most robust and reproducible
      intervention for slowing aging, and maintaining health and vitality in animals.
      Previous studies found that CR is associated with changes in specific biomarkers
      in monkeys that were also associated with reduced risk of mortality in healthy
      men. In this study we examine the association between other potential biomarkers
      related to CR and extended lifespan in healthy humans. METHODS: Based on the
      Baltimore Longitudinal Study of Aging, "long-lived" participants who survived to
      at least 90 years of age (n=41, cases) were compared with "short-lived"
      participants who died between 72-76 years of age (n=31, controls) in the nested
      case control study. Circulating levels of ghrelin, insulin, leptin, interleukin
      6, adiponectin and testosterone were measured from samples collected between the
      ages 58 to 70 years. Baseline differences between groups were examined with t
      test or Wilcoxon test, and mixed effects general linear model was used for a
      logistic model to differentiate the two groups with multiple measurements on some
      subjects. RESULTS: At the time of biomarkers evaluation (58-70 yrs), none of the
      single biomarker levels was significantly different between the two groups.
      However, after combining information from multiple biomarkers by adding the z
      transformed values, the global score differentiated the long- and short-lived
      participants (p=0.05). CONCLUSIONS: In their sixties, long-lived and short-lived
      individuals do not differ in biomarkers that have been associated with CR in
      animals. However, difference between the groups was only obtained when multiple
      biomarker dysregulation was considered.

PMID- 21743293
TI  - MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by
      co-regulating BMP signaling.
AB  - Osteogenic differentiation of mesenchymal stem cells (MSCs) is a complex process,
      which is regulated by various factors including microRNAs. Our preliminary data
      showed that the expression of endogenous miR-20a was increased during the course
      of osteogenic differentiation. Simultaneously, the expression of osteoblast
      markers and regulators BMP2, BMP4, Runx2, Osx, OCN and OPN was also elevated
      whereas adipocyte markers PPARgamma and osteoblast antagonist, Bambi and Crim1,
      were downregulated, thereby suggesting that miR-20a plays an important role in
      regulating osteoblast differentiation. To validate this hypothesis, we tested its
      effects on osteogenic differentiation by introducing miR-20a mimics and
      lentiviral-miR20a-expression vectors into hMSCs. We showed that miR-20a promoted
      osteogenic differentiation by the upregulation of BMP/Runx2 signaling. We
      performed bioinformatics analysis and predicted that PPARgamma, Bambi and Crim1
      would be potential targets of miR-20a. PPARgamma is a negative regulator of
      BMP/Runx2 signaling whereas Bambi or Crim1 are antagonists of the BMP pathway.
      Furthermore, we confirmed that all these molecules were indeed the targets of miR
      20a by luciferase reporter, quantitative RT-PCR and western blot assays.
      Similarly to miR-20a overexpression, the osteogenesis was enhanced by the silence
      of PPARgamma, Bambi or Crim1 by specific siRNAs. Taken together, for the first
      time, we demonstrated that miR-20a promoted the osteogenesis of hMSCs in a co
      regulatory pattern by targeting PPARgamma, Bambi and Crim1, the negative
      regulators of BMP signaling.

PMID- 21743294
TI  - Informed consent in vaccination in India: medicolegal aspects.
AB  - The doctrine of informed consent forms an integral part of any doctor-patient
      relationship. It serves two-fold as it develops trust and confidence in the
      patient for the doctor after being told about the plan of action; conversely the
      doctor can carry out planned medical interventions in a more composed manner,
      being confident in the protection of this doctrine if anything untoward occurs.
      Informed consent gives a blanket shield against compensation and criminal
      negligence charges filed by patients if the doctor has not deviated from standard
      practices of treatment or intervention or if no evidence of mal intention is
      forthcoming. Informed consent is applicable in most of the treatment modalities
      in which any intervention/invasive procedure is to be done or if any risk of
      complication is well known or documented. Surprisingly, even when serious life
      threatening complications are not only reported but on a steady rise due to
      vaccines, informed consent in vaccination is neither in vogue nor practice. Even
      in the US, there is no federal requirement for informed consent before
      vaccination, even though National Childhood Vaccine Injury Act and the Vaccine
      Compensation Amendments are in place. This paper attempts to present an overall
      comment on the necessity of informed consent before any vaccination especially in
      the Indian context in the backdrop of the beginning of vaccine compensation
      claims and litigation against the complications of vaccination in India.

PMID- 21743295
TI  - Drosophila glutamate receptor mRNA expression and mRNP particles.
AB  - The processes controlling glutamate receptor expression early in synaptogenesis
      are poorly understood. Here, we examine glutamate receptor (GluR) subunit mRNA
      expression and localization in Drosophila embryonic/larval neuromuscular
      junctions (NMJs). We show that postsynaptic GluR subunit gene expression is
      triggered by contact from the presynaptic nerve, approximately halfway through
      embryogenesis. After contact, GluRIIA and GluRIIB mRNA abundance rises quickly
      approximately 20-fold, then falls within a few hours back to very low levels.
      Protein abundance, however, gradually increases throughout development. At the
      same time that mRNA levels decrease following their initial spike, GluRIIA,
      GluRIIB, and GluRIIC subunit mRNA aggregates become visible in the cytoplasm of
      postsynaptic muscle cells. These mRNA aggregates do not colocalize with eIF4E,
      but nevertheless presumably represent mRNP particles of unknown function.
      Multiplex FISH shows that different GluR subunit mRNAs are found in different
      mRNPs. GluRIIC mRNPs are most common, followed by GluRIIA and then GluRIIB mRNPs.
      GluR mRNP density is not increased near NMJs, for any subunit; if anything, GluR
      mRNP density is highest away from NMJs and near nuclei. These results reveal some
      of the earliest events in postsynaptic development and provide a foundation for
      future studies of GluR mRNA biology.

PMID- 21743296
TI  - Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel
      biomarker discovery.
AB  - Esophageal squamous cell carcinoma (ESCC) is among the top ten most frequent
      malignancies worldwide. In this study, our objective was to identify potential
      biomarkers for ESCC through a quantitative proteomic approach using the isobaric
      tags for relative and absolute quantitation (iTRAQ) approach. We compared the
      protein expression profiles of ESCC tumor tissues with the corresponding adjacent
      normal tissue from ten patients. LC-MS/MS analysis of strong cation exchange
      chromatography fractions was carried out on an Accurate Mass QTOF mass
      spectrometer, which led to the identification of 687 proteins. In all, 257
      proteins were identified as differentially expressed in ESCC as compared to
      normal. We found several previously known protein biomarkers to be upregulated in
      ESCC including thrombospondin 1 (THBS1), periostin 1 (POSTN) and heat shock 70
      kDa protein 9 (HSPA9) confirming the validity of our approach. In addition,
      several novel proteins that had not been reported previously were identified in
      our screen. These novel biomarker candidates included prosaposin (PSAP), plectin
      1 (PLEC1) and protein disulfide isomerase A 4 (PDIA4) that were further validated
      to be overexpressed by immunohistochemical labeling using tissue microarrays. The
      success of our study shows that this mass spectrometric strategy can be applied
      to cancers in general to develop a panel of candidate biomarkers, which can then
      be validated by other techniques.

PMID- 21743297
TI  - Hyperthermia increases the therapeutic efficacy of survivinT34A in mouse tumor
      models.
AB  - The use of survivinT34A mutant targeted disruption of survivin, the strongest
      inhibitor of apoptosis protein overexpressed in tumors, has proved a promising
      strategy for advanced cancers. However, hyperthermia, as a cytotoxic enhancer,
      regularly activates the expression of survivin to counteract the heat-induced
      antitumor activity. Here, we investigated the combinational antitumor effect by
      using liposome-encapsulated mouse survivinT34A and hyperthermia in mouse models.
      We observed that the combination treatment of surivinT34A and hyperthermia
      significantly increased the growth inhibition and apoptosis of tumor cells in
      vitro compared with single treatment or other controls, which was similar to the
      effect of survivin silencing in combination with hyperthermia. Moreover, the
      inhibition of tumor growth in vivo was also remarkably enhanced by combination of
      surivinT34A and hyperthermia when compared with other treatments. Naturally, the
      tumor tissues in combination treatment presented the larger necrosis-like areas,
      more apoptotic cells and less microvessel density. Our findings suggest that the
      antitumor efficacy of survivin disruption can be enhanced by hyperthermia, which
      might be a new feasible approach for cancer therapy.

PMID- 21743298
TI  - Anticancer biology of Azadirachta indica L (neem): a mini review.
AB  - Neem (Azadirachta indica), a member of the Meliaceae family, is a fast growing
      tropical evergreen tree with a highly branched and stout, solid stem. Because of
      its tremendous therapeutic, domestic, agricultural and ethnomedicinal
      significance, and its proximity with human culture and civilization, neem has
      been called "the wonder tree" and "nature's drug store." All parts of this tree,
      particularly the leaves, bark, seed-oil and their purified products are widely
      used for treatment of cancer. Over 60 different types of biochemicals including
      terpenoids and steroids have been purified from this plant. Pre-clinical research
      work done during the last decade has fine-tuned our understanding of the
      anticancer properties of the crude and purified products from this plant. The
      anticancer properties of the plant have been studied largely in terms of its
      preventive, protective, tumor-suppressive, immunomodulatory and apoptotic effects
      against various types of cancer and their molecular mechanisms. This review aims
      at scanning scattered literature on "the anticancer biology of A. indica,"
      related toxicity problems and future perspectives. The cogent data on the
      anticancer biology of products from A. indica deserve multi-institutional
      clinical trials as early as possible. The prospects of relatively cheaper cancer
      drugs could then be brighter, particularly for the under-privileged cancer
      patients of the world.

PMID- 21743299
TI  - MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma
      multiforme.
AB  - Aberrant expression of microRNAs (miRNAs) has been implicated in cancer
      initiation and progression. In this study, we found that microRNA-34a (miR-34a)
      is significantly downregulated in glioblastoma multiforme (GBM) specimens
      compared with normal brain tissues. Growth curve and colony formation assays
      revealed that miR-34a suppresses proliferation of U373MG and SHG44 glioblastoma
      cells. Overexpression of miR-34a could induce apoptosis of glioblastoma cells.
      Also, we identified notch1 as a direct target gene of miR-34a. Knockdown of
      notch1 showed similar cellular functions as overexpression of miR-34a both in
      vitro and in vivo. Collectively, our findings show that miR-34a is downregulated
      in GBM cells and inhibits GBM growth by targeting notch1.

PMID- 21743300
TI  - Mitochondrial elongation during autophagy: a stereotypical response to survive in
      difficult times.
AB  - Mitochondrial morphological and structural changes play a role in several
      cellular processes, including apoptosis. We recently reported that mitochondrial
      elongation is also critical to sustain cell viability during macroautophagy.
      During macroautophagy unopposed mitochondrial fusion leads to organelle
      elongation both in vitro and in vivo. Longer mitochondria are protected from
      being degraded and possess more cristae where activity of the ATP synthase is
      increased, optimizing ATP production in times of nutrient restriction.

PMID- 21743301
TI  - New weapons in the war on tuberculosis.
AB  - Tuberculosis continues to be a global threat. Efforts to eradicate this disease
      are hampered by the long course and potential toxicity of currently available
      treatment regimens, the increasing prevalence of tuberculosis-HIV coinfection,
      the evolution of drug resistant organisms, and the lack of a highly effective
      vaccine. Recent studies have suggested methods to improve the cost effectiveness
      of existing treatment strategies. Decreasing the relapse rate among high-risk
      individuals by extending therapy can be balanced by the cost savings of self
      administered therapy for low-risk individuals. For the first time in over 30
      years, new medications are flowing through the drug discovery pipeline. New
      agents with activity against slowly dividing bacilli have the potential to
      shorten the duration of therapy. Many have a more favorable side-effect profile
      than currently available medications. And even extensively drug-resistant
      organisms will be susceptible to these secret weapons. The fully sequenced genome
      of Mycobacterium tuberculosis has been exploited to develop safer and more
      effective candidate vaccines. Highly immunogenic mycobacterial fragments, revved
      up versions of the existing vaccine, and toned-down versions of M. tuberculosis
      are all in various phases of clinical testing. This expanded arsenal has the
      potential to deliver a fatal blow to one of humanity's greatest enemies.

PMID- 21743303
TI  - Are we facilitating therapeutic innovation?

PMID- 21743305
TI  - Current world literature.

PMID- 21743306
TI  - Nutrition and metabolism.

PMID- 21743307
TI  - Genetics and molecular biology: fatty acids and endoplasmic reticulum stress.

PMID- 21743308
TI  - Lipid metabolism: the significance of plasma proprotein convertase subtilisin
      kexin type 9 in the elucidation of complex lipid disorders.

PMID- 21743309
TI  - Hyperlipidemia and cardiovascular disease: triglycerides - a revival of
      cardiovascular risk factor?

PMID- 21743310
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 21743311
TI  - Therapy and clinical trials: aggressive statin therapy versus combined and
      emerging approaches.

PMID- 21743312
TI  - Heavy-chain amyloidosis in TGFBI-negative and gelsolin-negative atypical lattice
      corneal dystrophy.
AB  - PURPOSE: An atypical case of late-onset lattice corneal dystrophy is described in
      a 61-year-old man without a family history of eye disease. Mutational analysis of
      the TGFBI gene excluded any pathogenic sequence variants. However, 2 years later,
      renal impairment and nephrotic syndrome were diagnosed, resulting in a diagnosis
      of systemic heavy-chain amyloidosis. METHODS: Slit-lamp examination, corneal
      photography, and in vivo confocal microscopy were performed. General systemic
      evaluation included blood and urine assessment, bone marrow and renal biopsies,
      and cardiologic evaluation. A DNA sample underwent initial mutational analysis of
      TGFBI and, subsequently, gelsolin. The renal biopsy sample was subject to direct
      protein sequencing by mass spectrometry. RESULTS: A bilateral, atypical, fine,
      midperipheral lattice corneal dystrophy with minor central subepithelial scarring
      was clinically characterized. Subsequently, abnormal renal functions with
      proteinuria, IgG lambda paraproteinemia, extensive deposition of amyloid in renal
      glomeruli, and increased plasma cells in bone marrow were identified. No
      pathogenic sequence mutations were identified in TGFBI or the gelsolin genes.
      Direct protein sequencing by mass spectrometry showed amyloid to be heavy-chain
      deposition rather than the more usual light-chain deposition. CONCLUSIONS:
      Atypical midperipheral lattice corneal dystrophy presenting with adult onset and
      negative family history should arouse suspicion for an association with
      paraproteinemias or amyloidosis. Exclusion of TGFBI mutations should alert the
      clinician to the possibility of potentially life-threatening conditions, with
      referral for careful systemic evaluation.

PMID- 21743313
TI  - Sodium hyaluronate gel as mitomycin C vehicle to reduce potential endothelial
      toxicity in pterygium surgery.

PMID- 21743315
TI  - Graft detachment after descemet stripping endothelial keratoplasty: when to
      rebubble?

PMID- 21743316
TI  - Coronary computed tomography angiography.
AB  - PURPOSE OF REVIEW: Significant limitations exist for traditional noninvasive
      cardiac imaging with regard to equivocal or indeterminate findings that result in
      repetitive testing or unnecessary referral to invasive coronary angiography
      (ICA). Recent hardware and software advances in multislice computed tomography
      angiography have achieved high spatial and temporal resolution to allow accurate
      noninvasive assessment of coronary arteries. This poses a paradigm shift in
      management of patients with suspected coronary artery disease (CAD). RECENT
      FINDINGS: Multicenter studies showed that coronary computed tomography
      angiography (CCTA) has a very high diagnostic accuracy, and, in particular, a
      very high negative predictive value (>98%) in detecting coronary stenosis when
      compared with ICA. In addition to its diagnostic ability, recent evidence-based
      outcome data have also validated the value of CCTA in predicting cardiac events.
      Absence of CAD on CCTA conveys excellent prognosis, whereas increasing disease
      severity and extent are associated with worsening outcome. Furthermore, CCTA
      allows comprehensive assessment of coronary stenosis, plaque burden, left
      ventricular morphology, function, perfusion and viability. One concern with CCTA
      is the issue of ionizing radiation exposure. Recent technical progress allows
      dramatic reduction of radiation dose. The newest generation scanner is capable of
      producing CCTA of diagnostic quality with a dose of less than 1 mSv. A
      multisociety guideline for appropriate clinical indications for cardiac computed
      tomography was recently published. SUMMARY: When used appropriately, CCTA has
      been established as a valid noninvasive imaging alternative to ICA in selected
      patients at low to intermediate risk of CAD.

PMID- 21743317
TI  - Optimizing outcome after cardiac arrest.
AB  - PURPOSE OF REVIEW: To discuss recent data relating to survival rates after
      cardiac arrest and interventions that can be used to optimize outcome. RECENT
      FINDINGS: A recent analysis of 70 studies indicates that following out-of
      hospital cardiac arrest (OHCA), 7.6% of patients will survive to hospital
      discharge (95% confidence interval 6.7-8.4). Following in-hospital cardiac
      arrest, 18% of patients will survive to hospital discharge. Survival may be
      optimized by increasing the rate of bystander cardiopulmonary resuscitation
      (CPR), which can be achieved by improving recognition of cardiac arrest,
      simplifying CPR and training more of the community. Feedback systems improve the
      quality of CPR but this has yet to be translated into improved outcome. One study
      has shown improved survival following OHCA with active compression-decompression
      CPR combined with an impedance-threshold device. In those who have no obvious
      extracardiac cause of OHCA, 70% have at least one significant coronary lesion
      demonstrable by coronary angiography. Although generally reserved for those with
      ST-elevation myocardial infarction, primary percutaneous coronary intervention
      may also benefit OHCA survivors with ECG patterns other than ST elevation. The
      term 'mild therapeutic hypothermia' has been replaced by the term 'targeted
      temperature management'; its role in optimizing outcome after cardiac arrest
      continues to be defined. SUMMARY: In several centres, survival rates following
      OHCA are increasing. All links in the chain of survival must be optimized if a
      good-quality neurological outcome is to be achieved.

PMID- 21743318
TI  - New diagnostic imaging modalities for pancreatic disease.
AB  - PURPOSE OF REVIEW: Imaging of the pancreas is critical for diagnostic decision
      making. Improvements in imaging have the potential to translate into improved
      patient outcomes by more accurate and rapid diagnosis. Evolving approaches to
      imaging for pancreatic diseases in the past year are reviewed. RECENT FINDINGS:
      The approach to patients with cystic lesions continues to focus on careful
      patient selection for surgery and targeted use of imaging and cyst sampling.
      Intraductal papillary mucinous neoplasm patients appear to have cancer risk
      independent of the neoplastic cyst itself. Imaging continues to focus on improved
      approaches to differentiation of inflammatory from neoplastic pancreatic mass
      lesions. SUMMARY: The approach to patients with suspected pancreatic disease
      continues to evolve, thanks to improved imaging. Recently developed diagnostic
      and treatment strategies show promise for improved patient outcomes.

PMID- 21743319
TI  - Endoscopic solutions for weight loss.
AB  - PURPOSE OF REVIEW: Gastroenterologists will likely play a critical role in the
      treatment of obesity and its comorbidities, as novel endoluminal approaches
      demonstrate their safety and efficacy over the coming years. Understanding the
      relative advantages and shortcomings of the endoscopic tools and procedures
      currently under investigation will provide the gastroenterologist with valuable
      insight into the future of endoscopic procedures for weight loss. RECENT
      FINDINGS: Endoscopic restrictive procedures, intestinal sleeves, and intragastric
      balloons have demonstrated short-term efficacy in inducing weight reduction and
      in reversing the comorbidities of obesity with an acceptable risk profile.
      Several endoscopic tools have also demonstrated effectiveness as revisional tools
      for reversing weight gain after bariatric surgery. SUMMARY: A plethora of
      endoscopic tools and procedures are under investigation for primary and
      revisional obesity management, and these may offer new weight loss options to a
      variety of different patient populations.

PMID- 21743320
TI  - A look at HIV journey: from dendritic cells to infection spread in CD4+ T cells.
AB  - PURPOSE OF REVIEW: Dendritic cells and their subsets are among the very first
      immune cells to tackle incoming pathogens and initiate innate and adaptive immune
      responses. During the past year, some studies investigating the early events
      occurring at mucosal sites, upon HIV infection, reinforced our view that the
      virus has evolved subtle strategies to hijack key cellular components in
      dendritic cells, thus leading to viral acquisition and dissemination while
      dampening or delaying antiviral responses. RECENT FINDINGS: In this review, we
      will detail recent research aimed at investigating the involvement of different
      dendritic cell subtypes on HIV transmission at mucosal sites, the events and
      cellular factors in dendritic cell guiding HIV trafficking, and polarization at
      the virological synapse. Furthermore, we will link some of these basic findings
      with current and novel therapeutic and prophylactic strategies targeting the
      early events of mucosal HIV transmission. SUMMARY: It is becoming evident that a
      better characterization of the early events of HIV transmission and the
      involvement of dendritic cell subtypes in this process would contribute to
      strengthen our efforts to improve the current therapeutic and prophylactic
      strategies.

PMID- 21743321
TI  - Dendritic cells at the interface of innate and adaptive immunity to HIV-1.
AB  - PURPOSE OF REVIEW: This review summarizes recent findings on how HIV-1 infection
      affects dendritic cells in their ability to elicit innate and adaptive immune
      responses. RECENT FINDINGS: The phenomenon describing a reduction of dendritic
      cell numbers in the blood of HIV-1-infected individuals has been expanded on in
      recent studies demonstrating that dendritic cells decline very early in primary
      infection and that there is a mobilization of semi-mature dendritic cells to
      lymph nodes. Recent data suggest that dendritic cells in lymph nodes are more
      prone to apoptosis, which correlates with disease progression. In addition,
      plasmacytoid dendritic cells isolated from blood showed a semi-mature phenotype
      after HIV-1 exposure, which coincided with persistent IFN-alpha secretion.
      Emerging data show that semi-mature dendritic cells induce regulatory T cells and
      suppress effector function. There may therefore be mechanisms by which HIV-1
      affects dendritic cell immune stimulation and, in doing so, interferes with the
      elicitation of anti-HIV-1 responses. SUMMARY: Understanding how dendritic cells
      are functionally altered during HIV-1 infection is crucial for the development of
      new immune-therapy strategies including approaches to target dendritic cells with
      antigen in vivo or ex vivo to induce efficient adaptive anti-HIV immunity.

PMID- 21743322
TI  - Innate signaling in HIV-1 infection of dendritic cells.
AB  - PURPOSE OF REVIEW: This review summarizes the current knowledge of innate
      signaling events that are involved in HIV-1 infection. We here focus on dendritic
      cells, which are among the first cells that encounter HIV-1 after exposure.
      RECENT FINDINGS: HIV-1 triggers multiple pattern recognition receptors on
      dendritic cells that facilitate infection and transmission to T cells. Triggering
      of the C-type lectin DC-SIGN induces signals that promote HIV-1 replication in
      dendritic cells and transmission to T cells. Similarly, dendritic cell
      immunoreceptor has been shown to bind HIV-1 and facilitate transmission to T
      cells. The cytosolic sensors TRIM5 and cyclophilin A recognize capsid proteins
      and activate antiviral responses to prevent HIV-1 infection. Moreover, activation
      of mammalian target of rapamycin (mTOR) by HIV downregulates autophagy preventing
      adaptive immune responses. SUMMARY: Dendritic cells express an array of pattern
      recognition receptors that are involved in HIV-1 infection. However, HIV-1
      dampens signaling by these receptors leading to suppressed responses or takes
      advantage of their signaling for its own benefit.

PMID- 21743323
TI  - Myeloid dendritic cells in HIV-1 infection.
AB  - PURPOSE OF REVIEW: Myeloid dendritic cells (mDCs) are pivotal players in HIV-1
      infection. They promote transmission and spread and at the same time are critical
      for recognizing HIV-1 and initiating immune responses to fight infection.
      Notably, their immunostimulatory capabilities can be harnessed to design better
      HIV-1 vaccines. In this review, advances in these areas of mDC-HIV-1 interactions
      are summarized. RECENT FINDINGS: New insights into HIV-1-induced dysfunction of
      mDCs and dysfunctional mDC effects on other cell types, as well as novel
      mechanisms of viral sensing by mDCs and their evasion by HIV-1, have been
      uncovered. These results emphasize the importance of mDCs in protection against
      HIV-1 infection. Targeting mDCs with vaccines and tailored adjuvants may improve
      the quality and anatomical location of elicited immune responses. SUMMARY:
      Understanding the multiplicity of HIV-1-dendritic cell interactions together with
      the numerous advances in targeted therapy and vaccination will help in the
      rational design of approaches to treat and block infection.

PMID- 21743324
TI  - Generalized immune activation and innate immune responses in simian
      immunodeficiency virus infection.
AB  - PURPOSE OF REVIEW: Chronic immune activation is a key factor driving the
      immunopathogenesis of AIDS. During pathogenic HIV/simian immunodeficiency virus
      (SIV) infections, innate and adaptive antiviral immune responses contribute to
      chronic immune activation. In contrast, nonpathogenic SIV infections of natural
      hosts such as sooty mangabeys and African green monkeys (AGMs) are characterized
      by low immune activation despite similarly high viremia. This review focuses on
      the role of innate immune responses in SIV infection. RECENT FINDINGS: Several
      studies have examined the role of innate immune responses to SIV as potential
      drivers of immune activation. The key result of these studies is that both
      pathogenic SIV infection of macaques and nonpathogenic SIV infections of natural
      hosts are associated with strong innate immune responses to the virus, high
      production of type I interferons by plasmacytoid dendritic cells, and
      upregulation of interferon-stimulated genes (ISGs). However, SIV-infected sooty
      mangabeys and AGMs (but not SIV-infected macaques) rapidly downmodulate the
      interferon response within 4-6 weeks of infection, thus resulting in a state of
      limited immune activation during chronic infection. SUMMARY: Studies in nonhuman
      primates suggest that chronic innate/interferon responses may contribute to AIDS
      pathogenesis. Further, the ability of natural host species to resolve innate
      immune responses after infection provides a novel avenue for potential
      immunotherapy.

PMID- 21743325
TI  - Extranodal natural killer/T-cell lymphoma: advances in the management.
AB  - PURPOSE OF REVIEW: Extranodal natural killer (NK)/T-cell lymphoma, nasal-type is
      a highly aggressive disease more frequent in Asia than in Western countries.
      There is no consensus treatment. The outcome depends on disease stage. Localized
      NK/T-cell lymphomas often respond to radiotherapy. In contrast, patients who have
      extensive disease or who relapse after radiotherapy have a very poor prognosis.
      Overall, long-term survival in these lymphomas tends to be inferior to that for
      other aggressive lymphomas. This review focuses on the new management modalities
      in light of advances in risk stratification, patient monitoring and treatment
      strategies. RECENT FINDINGS: Many parameters have been reported to correlate with
      prognosis and new staging systems have been elaborated. Detecting Epstein-Barr
      virus (EBV) in the bone marrow is important for staging and measuring EBV DNA in
      the serum improved monitoring response to therapy. Radiation modalities have been
      precised and new strategies combining radiation and chemotherapy have been
      proposed for patients with localized disease. The particular efficacy of L
      asparaginase in this disease has been confirmed and L-asparaginase-based regimens
      have been studied in prospective trials for patients with refractory, relapsing
      or disseminated disease with good results. Laboratory studies may point the way
      toward new therapeutic approaches. SUMMARY: Early-stage disease is treated by
      involved-field radiotherapy with adjuvant chemotherapy. L-Asparaginase-containing
      regimens are the mainstay of treatment for advanced or disseminated disease. The
      role of targeted therapies, autologous and allogeneic haematopoietic stem cell
      transplantation is yet to be clearly defined.

PMID- 21743326
TI  - Uterine carcinosarcoma.
AB  - PURPOSE OF REVIEW: To summarize the clinical characteristics, epidemiology, and
      treatment of uterine carcinosarcoma. RECENT FINDINGS: Recent studies have
      suggested that uterine carcinosarcomas are aggressive neoplasms that carry a poor
      prognosis even when diagnosed at an early stage. Treatment is typically surgical.
      The ideal adjuvant treatment remains unknown. A number of recent studies have
      examined the influence of radiation, chemotherapy, and combinations of
      chemotherapy and radiation for uterine carcinosarcoma. SUMMARY: Carcinosarcoma is
      an aggressive neoplasm. A number of studies are underway to determine the optimal
      adjuvant therapy for these tumors.

PMID- 21743327
TI  - Syncope during exercise: just another benign vasovagal event?
AB  - In general, syncope in children and adolescents is a benign event. Syncope during
      exercise may identify patients with a potentially fatal condition.
      Catecholaminergic polymorphic ventricular tachycardia is characterized by life
      threatening ventricular arrhythmias, usually polymorphic ventricular tachycardia
      or ventricular fibrillation, occurring under conditions of exercise or emotional
      stress. Catecholaminergic polymorphic ventricular tachycardia is a familial
      condition that presents with exercise-induced syncope or sudden death in children
      or young adults. Detailed evaluation should be considered for patients who have
      syncope during exercise, injure themselves during the fall (i.e., unprotected
      faint with no antecedent warning prodrome), or who have a family history of
      syncope, early sudden cardiac death, myocardial disease, or arrhythmias.

PMID- 21743328
TI  - Update on childhood and adolescent immunizations: selected review of US
      recommendations and literature: part 2.
AB  - PURPOSE OF REVIEW: To provide a clinically relevant synopsis of research findings
      regarding childhood and adolescent vaccines. RECENT FINDINGS: Vaccine coverage is
      relatively static or improving for the vaccines included in the 2010 annual
      harmonized immunization schedules. Providers should be reviewing patients'
      immunization records at each visit to take advantage of any opportunity to
      administer indicated, age-appropriate vaccines. There have been infectious
      disease outbreaks among highly immunized populations, although unvaccinated or
      undervaccinated individuals continue to play large roles in the spread of
      disease. Infants, many of whom are too young to be vaccinated, continue to bear a
      large disease burden, which underscores the importance of cocooning and, in some
      cases, vaccination of pregnant women. Influenza, measles, mumps, and rubella,
      varicella, hepatitis A, meningococcal conjugate, human papillomavirus, diphtheria
      and tetanus toxoids and acellular pertussis, and tetanus and diphtheria toxoids
      and acellular pertussis vaccines are reviewed in this second of two articles.
      SUMMARY: New research on childhood and adolescent vaccines is anticipated to
      shape the practice of pediatric providers. Research will continue to provide the
      science to optimize protection and to promote the health and well being of all
      children and adolescents.

PMID- 21743329
TI  - Mental capacity and consent to treatment in psychiatric patients: the state of
      the research.
AB  - PURPOSE OF REVIEW: The past three decades have seen the emergence of the field of
      decision-making capacity research. The growth has been such that there are
      several reviews covering a variety of subtopics within the field. The goal is to
      briefly summarize the state of research. RECENT FINDINGS: Most studies in this
      field use the MacArthur Competence Assessment Tools for the decisional capacity
      assessment. Studies in psychiatric patients indicate incapacity is common (20
      30%), but the majority are capable of making treatment decisions. Positive
      symptoms (hallucinations, delusions); negative symptoms (unusual thought content,
      conceptual disorganization); severity of symptoms; involuntary admission; lack of
      insight and treatment refusal were the stronger predictors for incapacity in
      acute and cognitive dysfunction in chronic patients. SUMMARY: Mental capacity has
      complex relationships with psychopathological variables, and these relationships
      are different according to diagnostic group. More research is needed to determine
      the clinical parameters related to the lack of capacity to make treatment
      decisions in psychiatric patients.

PMID- 21743330
TI  - Bronchiolitis and bronchial disorders in interstitial lung disease.
AB  - PURPOSE OF REVIEW: Bronchial and bronchiolar abnormalities in interstitial lung
      diseases (ILDs) are an issue often underestimated. However, new interstitial
      patterns with bronchiolar involvement are being described and the concept is
      still evolving. The scope of this review is to introduce a comprehensive approach
      to airway disorders in the context of ILDs, mainly from a pathologic perspective.
      RECENT FINDINGS: Recent studies have revealed significant inflammatory and
      structural alterations at the level of small airways in idiopathic interstitial
      pneumonias, which may participate in the lung-remodeling pathogenetic process. A
      suggested pathogenetic role of cigarette smoking for lung-remodeling in smoking
      related ILDs is further investigated, and unclassified fibrosis as a prominent
      feature in lung biopsy specimens of smokers has been established. New targeted
      therapies for lymphangioleiomyomatosis based on molecular and biologic properties
      of the disease are currently undergoing clinical trials. Combined pharmaceutical
      and interventional therapeutic regimens are of growing concern for refractory
      airway lesions in sarcoidosis. The application of volumetric high-resolution
      computed tomography (HRCT) chest scanning with acquisition of expiratory images
      provides valuable information about the involvement of small airways in ILDs.
      SUMMARY: The imaging and pathologic focus on airway abnormalities in ILDs make
      them an integral part of their pathology with a significant pathogenetic role in
      interstitial processes and variable contribution to the functional status of
      patients.

PMID- 21743331
TI  - The incidence of recurrent venous thromboembolism and chronic thromboembolic
      pulmonary hypertension following a first episode of pulmonary embolism.
AB  - PURPOSE OF REVIEW: Pulmonary embolism is the most serious complication of venous
      thromboembolism, with an elevated case/fatality rate. Patients who survived a
      first episode of pulmonary embolism should be evaluated for the risk of
      recurrence and of chronic thromboembolic pulmonary hypertension (CTEPH). RECENT
      FINDINGS: The risk of recurrence is higher in patients with unprovoked pulmonary
      embolism than in those with transient risk factors. Persistent risk factors, such
      as active cancer and antiphospholipid antibodies, are associated with high risk
      of recurrence. Recently, elevated D-dimer levels after discontinuation of therapy
      have been identified as a risk factor for recurrence. CTEPH is characterized by
      intravascular organization of emboli and occurs in 0.5-1% of cases. Some patients
      with CTEPH have impaired fibrinolysis, likely due to a structural abnormality of
      fibrin or fibrin clot. Echocardiography often reveals signs of pulmonary
      hypertension. This should be confirmed by direct measurement of pulmonary artery
      pressures at right heart catheterization. SUMMARY: CTEPH patients should receive
      life-long anticoagulation for preventing recurrent pulmonary embolism. Pulmonary
      endarterectomy is the treatment of choice for patients with proximal pulmonary
      vascular occlusion. Patients with predominantly distal pulmonary vascular
      occlusion are candidates for pharmacological treatment. All patients with
      unprovoked pulmonary embolism should be evaluated for long-term anticoagulation.

PMID- 21743332
TI  - Cardiac sarcoidosis: a review 2011.
AB  - PURPOSE OF REVIEW: Cardiac involvement in sarcoidosis is not always associated
      with a wide spread of disease, but when present, has been linked with a
      relatively poor prognosis. This review will delve into new genetic associations,
      recently reported clinical manifestations and complementary radiographic tools
      that aid with diagnosis and follow-up. RECENT FINDINGS: Clinical manifestations,
      diagnosis and management remain an intricate maze.Genetic predisposition and
      associations that include HLA class II molecules and polymorphisms in tumor
      necrosis factor-alpha have been reported due in part to weakened arguments
      suggesting autoimmune disorders or dysregulation. In addition, further
      symptomatologies have been reported that assist with diagnosis.Radiographic tools
      including Microvolt T wave alternans, cardiovascular magnetic resonance, late
      gadolinium enhancement and cardiac assist devices, recently being used, are
      shedding some light on the diagnostic challenges. SUMMARY: Cardiac involvement in
      sarcoidosis remains a challenging dilemma, relying on a combination of clinical
      findings and imaging abnormalities because no single diagnostic test has yet
      emerged with a high degree of specificity and sensitivity. Given its life
      threatening nature, prompt establishment of a diagnosis, an aggressive management
      strategy and devices to prolong life should be pursued.

PMID- 21743333
TI  - Clinical application of the cardioprotective effects of volatile anaesthetics:
      CON--total intravenous anaesthesia or not total intravenous anaesthesia to
      anaesthetise a cardiac patient?
AB  - Although volatile anaesthetics show strong and easily reproducible
      cardioprotective effects in animal experiments, these effects are less obvious in
      clinical settings. Indeed, more than a decade after the first human clinical
      study, the number of publications has increased extensively, but the encouraging
      results from previous studies in terms of myocardial protection have failed to
      translate into an improvement in survival or a decrease the incidence of
      myocardial infarction. No consensus on the modalities of administration of
      volatile anaesthetics has been agreed and when the experimental protocols are
      transposed into daily clinical practice, their cardioprotective effects are still
      weak. The reasons for the disparities between experimental and clinical studies
      will be reviewed here, especially the role of patients' co-morbidities and
      medications as well as the limitations of the main positive clinical trials.
      Recent data showing anti-inflammatory properties of propofol will also be
      explained. One of the most important clinical benefits of propofol is that it can
      be used by target-controlled or continuous infusion for anaesthesia and sedation
      throughout the surgical and critical care periods without the risk of a
      transition failure. Further large multi-centre clinical investigations are still
      required.

PMID- 21743334
TI  - A multidisciplinary approach to intensive care medicine.

PMID- 21743335
TI  - Cognitive deficits after systemic induction of inducible nitric oxide synthase: a
      randomised trial in rats.
AB  - BACKGROUND: Nitric oxide acts as an important neurotransmitter as well as a
      sepsis mediator. During sepsis, high levels of nitric oxide, produced by the
      inducible form of the nitric oxide synthase (iNOS), may lead to disturbances
      concerning these conflicting roles and cause septic encephalopathy. To evaluate
      this theory, we aimed at first, to demonstrate cognitive dysfunction in a rat
      model based on systemic iNOS induction; second, to elucidate molecular
      mechanisms; and third, to prevent cognitive deficits in our sepsis model.
      METHODS: We used a rat systemic inflammation model that is based on the induction
      of iNOS by heat-killed Corynebacterium parvum in different doses (30 or 60 mg
      kg). NO2/NO3 plasma levels were measured to prove iNOS induction. Cognitive
      performance was investigated. In brain tissue, NOS protein and NOS activity were
      determined. To prevent cognitive deficits, two groups of rats received L-N-(1
      Iminoethyl)-lysine (L-NIL), a specific iNOS inhibitor in the drinking water.
      RESULTS: The rats[Combining Acute Accent] cognitive performance, that is, short
      term memory as well as long-term memory was impaired in C. parvum rats with a
      peak at the third day after injection in the 60 mg kg group. At the same day,
      neuronal NOS (nNOS)-protein content in the prefrontal cortex was reduced in C.
      parvum rats. nNOS activity was also reduced in C. parvum rats. The cognitive
      deficit in short-term memory could be prevented by L-NIL. CONCLUSION: We
      demonstrate early, reversible cognitive deficits in a rat model of systemic
      inflammation with increased systemic iNOS activity. As systemic inhibition of
      iNOS activity prevented rats from the deficit in short-term memory, an
      involvement of systemic iNOS induction in this deficit is likely. Whether the
      reduced nNOS-protein expression and nNOS activity are connected to systemic iNOS
      induction, however, remains unclear.

PMID- 21743336
TI  - Evaluation of the Bonfils intubating fibrescope for predicted difficult
      intubation in awake patients with ear, nose and throat cancer.
AB  - BACKGROUND AND OBJECTIVE: Anaesthesiologists are regularly faced with difficult
      tracheal intubation. The objective of the study was to evaluate the feasibility
      and tolerability of tracheal intubation with the Bonfils intubating fibrescope in
      awake adult patients with predicted difficult intubation undergoing cancer
      surgery in an ear, nose and throat unit. METHODS: Intubation was performed under
      local anaesthesia and remifentanil sedation with spontaneous ventilation. The
      primary endpoint was the proportion of intubations which met the following
      quality requirements: successful intubation (<= 2 attempts and duration <180 s)
      and good tolerability (Fahey scale <2). Secondary endpoints included the
      operational problems encountered and patients' perception of the procedure
      immediately and 7 days after the intervention. Using a one-stage Fleming design,
      32 patients were required to complete the study. Forty-one eligible adult
      patients were enrolled. RESULTS: Between February 2008 and March 2009, the
      primary endpoint could be evaluated in 33 patients. Quality requirements were met
      in 26 patients (78.8%) and not met in seven patients (five were intubated with
      the Bonfils fibrescope and two using another technique). Difficulties were
      reported in 13 patients (39.4%). Eighty-four percent of the patients had a good
      or very good perception of the intubation shortly after the procedure, and 91%
      after 7 days. CONCLUSION: Tracheal intubation using the Bonfils intubating
      fibrescope was successful in almost all patients (93.9%). The 78.8% incidence of
      interventions which met the quality requirements is high in the context of ear,
      nose and throat cancer and acceptable in current clinical practice. In ear, nose
      and throat cancer patients who do not require nasopharyngeal intubation and in
      whom orotracheal intubation is predicted to be difficult, the use of the Bonfils
      intubating fibrescope is safe, effective and well tolerated. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT01070537, URL:
      http://clinicaltrials.gov/ct2/show/NCT01070537?term=bonfils&rank=2.

PMID- 21743337
TI  - Empowering leadership, perceived organizational support, trust, and job burnout
      for nurses: a study in an Italian general hospital.
AB  - BACKGROUND: A strong nursing leadership that instills trust in the leader and in
      the organization is an important component for an effective leadership,
      particularly for health care organizations, because trust defines the heart of
      health care workplaces by promoting patient safety, excellence in care,
      recruitment, and retention of the nursing staff. PURPOSE: This study aimed to
      test the impact of perceived empowerment leadership style expressed by the nurse
      supervisor, nurses' perceived organizational support, trust in the leader, and
      trust in the organization on nurses' job burnout. METHODOLOGY/APPROACH: A group
      of 273 nurses from an Italian public general hospital took part in a cross
      sectional study on a voluntary basis by filling out an anonymous questionnaire.
      FINDINGS: Empowering leadership was an important predictor of trust in the
      leader. Trust in the organization was influenced by perceived organizational
      support and by the Informing dimension of the empowering leadership style. Trust
      in the leader and trust in the organization showed a negative impact on job
      burnout and also mediated the effects of some empowering leadership dimensions
      and perceived organizational support on job burnout. PRACTICE IMPLICATIONS: The
      central role of trust in health care organizations was corroborated, as well as
      the beneficial effects of adopting specific features of empowerment leadership
      behaviors toward the nursing staff. Empowering leadership could be successfully
      proposed in training programs directed to nurses' supervisors and health care
      managers.

PMID- 21743338
TI  - Transcatheter aortic valve implantation.
AB  - Older adults with progressively worsening aortic valve stenosis are limited in
      their treatment options. Conventional treatment replaces the aortic valve via
      open-heart surgery, introducing numerous risks and increased mortality in older
      populations with comorbidities. In recent years, however, transcatheter aortic
      valve implantation (tAVI) has become a viable option for symptomatic, nonsurgical
      candidates. Although tAVI is available only to a select population, early
      randomized and nonrandomized clinical trials are offering insight into the new
      therapy, with promising results as this treatment continues to evolve. PURPOSE:
      This article examined the progression of tAVI therapies, from first-generation to
      third-generation devices and through 4 studies that address the utility of tAVI
      in symptomatic, nonsurgical candidates, in an effort to prepare nurses in the
      management of this newly emerging patient population. METHODS: A literature
      search was conducted of studies within the past 5 years that address transfemoral
      tAVI in adult populations. Transapical approaches were excluded. RESULTS: Early
      outcomes demonstrate that successful implantation can improve valvular function
      and patient functional status. Nurses play a critical role in patient education
      and monitoring both before and after tAVI. CONCLUSIONS: With increasing life
      expectancies and a prediction that many aging adults with aortic valve stenosis
      will be limited to tAVI, nurses need to gain familiarity with this novel therapy
      and its role in patient outcomes.

PMID- 21743339
TI  - Assessment of commonly available education materials in heart failure clinics.
AB  - BACKGROUND: Health literacy (HL) is an established independent predictor of
      cardiovascular outcomes. Approximately 90 million Americans have limited HL and
      read at the fifth grade level or lower. Therefore, we sought to determine the
      suitability and readability level of common cardiovascular patient education
      materials (PEM) related to heart failure and heart-healthy lifestyle. METHODS AND
      RESULTS: The suitability and readability of written PEMs were assessed using the
      suitability assessment of materials (SAM) and Fry readability formula. The SAM
      criteria are composed of the following categories: message content, text
      appearance, visuals, and layout and design. We obtained a convenience sample of
      18 English-written cardiovascular PEMs freely available from major health
      organizations. Two reviewers independently appraised the PEMs. Final suitability
      scores ranged from 12% to 87%. Readability levels ranged between 3rd and 15th
      grade level; the average readability level was 8th grade. Ninety-four percent of
      the PEMs were rated either superior or adequate on text appearance, but 50% or
      more of the PEMs were rated inadequate on each of the other categories of the SAM
      criteria. Only 2 (11%) PEMs had the optimum suitability score of 70% or higher
      and 5th grade or lower readability level suitable for populations with limited
      HL. CONCLUSIONS: Commonly available cardiovascular PEMs used by some major
      healthcare institutions are not suitable for the average American patient. The
      true prevalence of suboptimal PEMs needs to be determined because it potentially
      negatively impacts optimal healthcare delivery and outcomes.

PMID- 21743340
TI  - Exercise behavior in adolescents with mild congenital heart disease.
AB  - BACKGROUND AND RESEARCH OBJECTIVES: Most children with congenital heart disease
      (CHD) are expected to survive to adolescence and adulthood owing to medical
      advances and care management. These adolescents need to be well informed about
      their exercise capacity and take greater personal responsibility for their
      exercise behavior as they mature. The aims of this study were to compare the
      amount and intensity of exercise engaged in by male and female adolescents with
      mild CHD while on summer vacation and during the academic semester and to
      determine the extent to which their exercise behavior met cardiologists'
      recommendations, based on New York Heart Association functional classification.
      PARTICIPANTS AND METHODS: A repeated-measure design was used to evaluate exercise
      behavior in 126 adolescents 12 to 18 years old with mild CHD from the outpatient
      cardiology departments of 3 medical centers in Taiwan. Exercise, classified as
      mild, moderate, or vigorous, was evaluated during summer vacation and during the
      fall semester using a 7-day self-reported exercise log. RESULTS AND CONCLUSIONS:
      Patients engaged in significantly more mild and total exercise during summer
      vacation than they did during the fall semester. They also engaged in
      significantly less vigorous exercise during summer vacation than they did in the
      fall semester. Female respondents engaged in significantly less moderate (P =
      .019), vigorous (P < .001), and total (P = .015) exercise than did their male
      counterparts but showed no difference in mild exercise. During the summer and
      fall, nearly 50% of the adolescents followed their cardiologist's recommendations
      for exercise. Adolescents with mild CHD engaged in more exercise during summer
      vacation but engaged in more vigorous exercise during the fall semester.
      Approximately one half did not follow the exercise intensity recommended by
      cardiologists. Inadequate exercise patterns may lead to cardiovascular
      complications. Planned interventions related to exercise instruction are needed
      for adolescents with CHD.

PMID- 21743341
TI  - Sleep duration, snoring habits, and cardiovascular disease risk factors in an
      ethnically diverse population.
AB  - BACKGROUND: Lack of sleep has been associated with an increased risk for
      cardiovascular disease (CVD) and all-cause mortality, but the mechanisms are not
      fully understood. Prior research has often been conducted in select populations
      and has not consistently adjusted for confounders, especially psychosocial
      factors. OBJECTIVE: The aims of this study were to assess the association between
      sleep habits and established risk factors for CVD and to evaluate potential
      interactions by race and gender. METHODS: Participants were part of a CVD
      screening and educational outreach program in New York City. Free-living men
      older than 40 years and women older than 50 years (n = 371, mean age = 60 years,
      57% women, 60% racial/ethnic minorities) were systematically assessed for CVD
      risk (including traditional, lifestyle, and psychosocial risk factors) and
      completed a standardized questionnaire regarding sleep habits (including sleep
      duration and snoring). Lipids were analyzed by validated finger-stick technology.
      Stress at work and at home was assessed using a validated screening tool from the
      INTERHEART study. Associations between participants' sleep habits and CVD risk
      factors/demographic factors were assessed using multivariable logistic
      regression. RESULTS: The proportion of participants who reported sleeping less
      than 6 hours per night on average was 28%, and 52% of participants reported
      snoring. Sleeping less than 6 hours per night was significantly (P < .05)
      associated with female gender, being single, increased stress at home, increased
      financial stress, and low-density lipoprotein cholesterol (LDL-C) level. Gender
      modified the association between sleep duration and LDL-C level (P = .04):
      Sleeping less than 6 hours per night was significantly associated with reduced
      LDL-C level among women and increased LDL-C level among men. Snoring was
      significantly associated with low high-density lipoprotein cholesterol (HDL-C)
      level (<40 mg/dL for men/<50 mg/dL for women), being married, increased stress at
      work and at home, less than 30 minutes of exercise per day, less than 5 servings
      of fruits and vegetables per day, and being overweight/obese (body mass index
      >=25 kg/m). The association between snoring and low HDL-C level remained
      significant in logistic regression models adjusted for demographic confounders
      (odds ratio, 1.83; 95% confidence interval, 1.06-3.19) but not after adjustment
      for body mass index greater than 25 kg/m. CONCLUSIONS: Sleeping less than 6 hours
      per night was associated with several traditional and psychosocial CVD risk
      factors, and snoring was associated with low HDL-C level, likely mediated through
      overweight/obesity. These data may have significance for health care providers to
      identify individuals who may be at increased CVD risk based on sleep habits.

PMID- 21743342
TI  - Illness perceptions, coping strategies, and symptoms contribute to psychological
      distress in patients with recurrent symptomatic atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is a prevalent, life-complicating illness
      associated with psychological distress. Interventions to manage the psychological
      challenges of living with AF are needed. Evidence suggests that illness
      perceptions, coping strategies, and symptoms that contribute to psychological
      distress may be modified by psychoeducational interventions to reduce
      psychological distress. However, little is known about how illness perceptions,
      coping strategies, and symptoms contribute to psychological distress in patients
      with AF. OBJECTIVE: The aim of this correlational study guided by Levethal's
      Common Sense Model of Self-regulation was to identify the extent to which illness
      perceptions, coping strategies, symptom frequency, and symptom severity
      contributed to psychological distress in patients with recurrent symptomatic AF.
      The contribution of these factors was considered with respect to the effects of
      gender, age, type of AF, and time since AF diagnosis. METHODS: Participants (n =
      207; 56% male; 64.2 +/- 12.3 years old) completed the Illness Perception
      Questionnaire-Revised, the COPE Inventory, the Symptom Checklist-Frequency and
      Severity, and the Profile of Mood States. Data were analyzed using Pearson
      correlation and hierarchical multiple regression. RESULTS: Illness perceptions
      contributed most to psychological distress, followed by coping strategies and
      symptom frequency. Illness perceptions explained the largest portion of the total
      variance for the following: Tension-Anxiety, 44/56%; Depression-Dejection,
      38/50%; Fatigue-Inertia, 43/53%; Confusion-Bewilderment, 41/49%; Vigor-Activity,
      24/35%; and Total Mood Disturbance, 47/63%. Illness perceptions of AF as having
      serious consequences, a psychological cause, and perceived poor understanding of
      AF together contributed more (.47) to Total Mood Disturbance than did coping by
      focusing on emotion (.08) or symptom frequency (.06). CONCLUSIONS: Illness
      perceptions are important contributors to psychological distress in patients with
      AF. Assessment of patients' illness perceptions may reveal those that increase
      the risk for psychological distress. Research is warranted to evaluate
      interventions to modify psychological cause and consequence beliefs and to
      promote understanding of AF.

PMID- 21743343
TI  - A narrative study of women's early symptom experience of ischemic stroke.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Delayed arrival at the emergency department
      after the onset of ischemic stroke symptoms is an important reason for low tissue
      plasminogen activator administration rates. There is evidence that women arrive
      at the hospital later than do men, but little is known about women's experiences
      in the period between symptom onset and hospital arrival. The purpose of this
      naturalistic investigation using narrative methodology was to gain understanding
      of women's early symptom experience of ischemic stroke. SUBJECTS AND METHODS: The
      sample consisted of 9 women aged 24 to 86 years with an ischemic stroke within 1
      year of diagnosis. Data were collected using in-depth interviews in which
      participants were asked to tell the story of their stroke from the moment they
      noticed the symptoms until they arrived at the hospital. Data were analyzed using
      sequential methods of narrative analysis. RESULTS AND CONCLUSIONS: The
      participants experienced stroke onset as the inability to carry out their
      accustomed activities in usual ways and as a process occurring over time rather
      than a discrete event. There was a tendency to objectify the body. Two
      participants considered stroke as a possible cause for their symptoms, and the
      other women attributed symptoms to everyday bodily experiences and/or other
      health conditions. Most participants did not perceive themselves at risk for
      stroke, although all but 1 woman had risk factors. For some women, stroke onset
      was different from their previous ideas about this event, and this was especially
      the case if a woman had prodromal symptoms. Decision making during early stroke
      flowed from women's evaluation of symptoms and the meaning of symptoms, and
      meaning was informed by a woman's life situation. The findings from this study
      may yield variables for future studies of cognitive, emotional, and behavioral
      predictors of hospital arrival time. There is a need for research on women's
      prodromal symptoms.

PMID- 21743344
TI  - Impact of nurse-initiated preoperative education on postoperative anxiety
      symptoms and complications after coronary artery bypass grafting.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) in high-risk patients is
      associated with significant perioperative complications and anxiety. Prevention
      of these postoperative complications and anxiety is important in the improvement
      of clinical outcomes following CABG. OBJECTIVE: The objective of the study was to
      evaluate the effect of nurse-initiated preoperative education and counseling on
      postoperative complications and anxiety symptoms following CABG. METHODS: In this
      prospective and randomized trial, 40 patients were divided into the study and
      control groups. All patients received standard preoperative and postoperative
      care, but the study group patients also completed a structured education and
      counseling course supervised by designated nurses 3 days before the surgery.
      Anxiety symptoms were assessed by Zung's self-rating anxiety scale (SAS) on the
      day of admission and at 3 days after the surgery. RESULTS: There was no
      statistically significant difference in the baseline characteristics or
      operational data between the 2 groups (P > .05). Following the surgery, the rate
      of complications such as lower extremity edema, urinary retention, constipation,
      respiratory infection, and deep venous thrombosis in the study group was lower
      than in the control group (P < .05). The mean postoperative SAS scores in the
      study group was lower than in the control group (40.1 [SD, 6.5] vs 48.9 [SD,
      7.3]; P = .01), and the proportion of patients with a SAS score greater than 40
      in the study group was also lower than in the control group (15% vs 45%, P =
      .041). CONCLUSIONS: Nurse-initiated preoperational education and counseling were
      associated with a reduced rate of perioperative complications and a reduced level
      of anxiety following CABG.

PMID- 21743345
TI  - Decisive situations affecting partners' support to continuous positive airway
      pressure-treated patients with obstructive sleep apnea syndrome: a critical
      incident technique analysis of the initial treatment phase.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Effective treatment of obstructive sleep apnea
      syndrome (OSAS) with continuous positive airway pressure (CPAP) can reduce
      morbidity and mortality, but adherence rates are low. The partner has an
      important role in supporting the patient, but this role may be adversely affected
      by difficulties during the early phase of the CPAP initiation. The aim of this
      study was to explore and describe decisive situations affecting partners' support
      to patients with OSAS and how the partners manage these situations during the
      initial phase of CPAP treatment. SUBJECTS AND METHODS: A qualitative descriptive
      design using critical incident technique was used. A total of 542 decisive
      situations affecting partners' support and 222 situations describing managing
      were collected by means of interviews with 25 strategically selected partners of
      patients with CPAP treated OSAS. RESULTS: Adverse effects, limited effect,
      practical and psychosocial problems, limited presence, and inappropriate
      initiation emerged as negative influences on the partners' support. A well
      functioning treatment, improvements, high motivation, and receiving support from
      others were identified as positive influences on the partners' support. The
      partner managed the situations by letting the patient handle the CPAP treatment
      by himself/herself, by handling the treatment together with the patient, or
      taking over the handling of CPAP treatment. CONCLUSION: Increased knowledge about
      the different situations that affect the partners' support negatively or
      positively and how these situations are managed by partners can be used in
      educational situations involving both patients and partners during CPAP
      initiation.

PMID- 21743346
TI  - Use of complementary therapies by individuals with or at risk for cardiovascular
      disease: results of the 2007 National Health Interview Survey.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) therapies are often used
      as adjuvants to conventional treatment by individuals with cardiovascular disease
      (CVD) or CVD risk factors, such as hypertension and high cholesterol. Patterns of
      use of CAM practices and products represent important data for health care
      providers in delivering adequate patient care. OBJECTIVE: This study compared CAM
      use among the US CVD and general population, as well as individuals with CVD risk
      factors (hypertension and/or high cholesterol), through secondary analyses of the
      2007 National Health Interview Survey data. METHODS: The analysis compared use of
      CAM by individuals with CVD (those individuals self-reporting a diagnosis of
      coronary heart disease; n = 1055), individuals with CVD risk factors (those
      individuals self-reporting a diagnosis of hypertension [n = 6849] or high
      cholesterol [n = 5808]), and individuals who self-report as not having CVD or CVD
      risk factors (n = 22 290). RESULTS: Use of complementary practices and products
      by patients with CVD and CVD risk factors is common and significantly greater
      than individuals without CVD in the general population. The most common
      categories of complementary modalities used by individuals with a self-reported
      diagnosis of CVD or CVD risk factors were natural products and mind-body
      practices. CONCLUSIONS: The diagnosis of CVD or CVD risk factors may be
      associated with the use of complementary practices and products.

PMID- 21743347
TI  - Intensive care nurses' perspectives of family-centered care and their attitudes
      toward family presence during resuscitation.
AB  - BACKGROUND: Family-centered care (FCC) has been cited as important to patient
      care; however, little is known about nurses' perspectives toward FCC. Family
      presence during resuscitation (FPDR) is an example of the implementation of FCC;
      however, nurses do not necessarily agree with FPDR, especially those from non
      Western countries. It is also unknown whether there is an association between
      FPDR and FCC. OBJECTIVES: The objective of the study was to determine (a) the
      attitudes of nurses toward FCC and FPDR and (b) whether there is an association
      between FCC and FPDR. SUBJECTS AND METHODS: A convenience sample of 96 Israeli
      intensive care unit and cardiovascular registered nurses completed 5
      questionnaires: a demographic data questionnaire, Nursing Activities for
      Communication With Families-Revised, Barriers to Providing Family-Centered Care
      Revised (Barriers), Nurses' Experiences of Family-Witnessed Resuscitation, and
      Attitudes to Family Presence During Resuscitation. Descriptive statistics and
      Pearson correlations were conducted. RESULTS: The item mean values for the
      Nursing Activities for Communication With Families-Revised and the Barriers
      scales were only 3.7 of 5 and a moderate 2.4 of 4, respectively. Only 19 of the
      sample (20%) had experienced FPDR, of which 17 reported a negative as opposed to
      a positive experience. Overall, nurses objected to FPDR (mean item score = 1.8 of
      5). No statistically significant relationship was found between FCC and FPDR. A
      significant negative correlation was found between the Barriers scale and FPDR (r
      = -0.36, P = .0001). CONCLUSION: Although FCC has moderate support, objection
      still remains to FPDR. Family presence during resuscitation has been used as an
      example of FCC, but at least in certain populations, this example might not be
      applicable. Increased education and policy changes should be encouraged to
      promote FCC and FPDR.

PMID- 21743348
TI  - Examining the interrelatedness of patient and spousal stress in heart failure:
      conceptual model and pilot data.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Recent research has highlighted the positive
      influence that spouses can have on patient outcomes. It is not clear whether
      patients and spouses influence each other's well-being reciprocally or whether
      spousal well-being affects the success of patients' disease management. Our goals
      were 2-fold: (a) to propose a conceptual framework to examine the reciprocity
      between patient and spouses' well-being, especially as it relates to disease
      management, and (b) to begin to assess the validity of this model using pilot
      data. SUBJECTS AND METHODS: Twenty-three veterans with heart failure (HF) and
      their spouses were recruited into a pilot cross-sectional observational study.
      Participants completed psychosocial surveys to assess depressive symptoms,
      caregiver burden, relationship satisfaction, and disease management. Descriptive
      analyses and bivariate correlations between these measures were calculated.
      RESULTS: Using standard cutoffs, analyses suggested clinically significant
      depressive symptoms in patients (Center for Epidemiological Studies-Depression
      score >16; mean, 21.8 [SD, 13]) and a high level of caregiver burden among
      spouses (Zarit Burden Interview score >15; mean, 22.4 [SD, 15.4]). Both patients
      and spouses reported high relationship satisfaction levels (Dyadic Adjustment
      Scale score >100; mean, 112.6 [SD, 26.5] and 115.9 [SD, 14.4], respectively). On
      average, patients reported poor disease management (Self-care of Heart Failure
      Index subscale <70 across all subscales: confidence = 53.3 [SD, 28.2];
      maintenance = 59.7 [SD, 17.3]; management = 54.0 [SD, 19.4]). Patient depressive
      symptoms were positively correlated with spouse depressive symptoms (r = 0.53)
      and caregiver burden (r = 0.64; all P's < .05). Spouses' depressive symptoms were
      additionally correlated with lower levels of perceived social support among
      patients (r = -0.47), poor patient relationship satisfaction (r = -0.51), and
      worse patient confidence in HF management (r = -0.48). Greater caregiver burden
      was associated with more patient disease complaints (r = 0.49), poorer patients'
      relationship satisfaction (r = -0.72), and poorer patients' perceived social
      support (r = -0.73). CONCLUSIONS: These results provide preliminary support to
      the proposed conceptual model. Further research is necessary to determine which
      spousal factors appear to be most relevant to disease management. Disease
      management interventions may benefit from engaging spouses in a way that enhances
      their role without adding to their burden.

PMID- 21743349
TI  - Attachment and infant night waking: a longitudinal study from birth through the
      first year of life.
AB  - OBJECTIVE: : Night wakings are common in infancy. Although a link between infant
      night wakings and attachment to the primary caregiver has been previously
      proposed, empirical support is limited so far. The aim of this longitudinal study
      was to examine the early history of night waking in infants who were later
      classified as securely or insecurely (avoidantly, resistantly, or disorganized)
      attached. METHODS: : Participants in the study were 193 infants and their
      mothers. Information on infant night wakings was collected with the use of daily
      sleep diaries for the first 6 months of life and again for 2 weeks at 12 months
      of age. Infant-mother attachment was assessed using the Strange Situation
      (Ainsworth et al, Patterns of Attachment: A Psychological Study of the Strange
      Situation. New York: Hillsdale; 1978) when the infants were 12 months of age.
      RESULTS: : Longitudinal regression analyses showed that, after controlling for
      many covariates, infants with an insecure-resistant attachment at 12 months of
      age awoke more during the night in their first 6 months of life than the other
      infants. Furthermore, infants with different attachment classifications developed
      different patterns of night wakings over the first 6 months, with the insecure
      avoidant infants waking the least toward the end of the 6 months. Hierarchical
      multiple regression analyses showed no associations between attachment and night
      wakings at 12 months of age. CONCLUSION: : This study is the first in showing
      that attachment at 12 months of age is related to infant night waking patterns in
      the first 6 months of life. Patterns of infant night wakings early in life
      apparently reflect the emerging attachment relationship.

PMID- 21743350
TI  - Psychosocial functioning and social cognitive processing in girls with Turner
      syndrome.
AB  - OBJECTIVE: Turner syndrome (TS) is a common genetic disorder caused by partial or
      complete absence of the second X chromosome in females and is associated with a
      characteristic neurocognitive profile traditionally described by discrepancy
      between verbal and performance IQ. Difficulties in social functioning have also
      been increasingly identified in this population. The purpose of this study was to
      examine elements of social competence and cognition in a pre-estrogen population
      of girls with TS. METHODS: The authors administered psychosocial and
      neurocognitive measures to examine metrics of social function and intelligence in
      a group of young girls with TS, pre-estrogen treatment (n = 42) and control peers
      (n = 32), aged between 3 and 12 years. RESULTS: Girls with TS demonstrated
      significantly decreased social competency on all dimensions of the Social
      Responsiveness Scale, with the exception of the Social Motivation subscale, where
      ratings were comparable with typically developing peers. Performance on social
      cognitive tasks was also impaired on NEPSY Memory for Faces and Theory of Mind
      tasks. Differences were further observed on Behavioral Assessment Scales for
      Children subscales of Hyperactivity, Atypicality, Attention, Social Skills,
      Activities of Daily Living, and Functional Communication. Group differences in
      social cognition or behavior remained significant after adjusting for verbal IQ.
      CONCLUSION: This study supports the hypothesis that young girls with TS who have
      not yet received estrogen treatment demonstrate significantly impaired social
      cognition. Improved understanding of differences in social competence and
      cognition can increase awareness and inform clinical approaches to identifying
      and treating social difficulties in individuals with TS.

PMID- 21743351
TI  - Sensory overresponsivity: prenatal risk factors and temperamental contributions.
AB  - OBJECTIVE: The study addresses risk factors and cause of pediatric sensory over
      responsivity (SOR) in a large sample of twins. At age 2 years, (a) the
      association of temperamental traits with concurrent SOR; (b) the association of
      prenatal complications with SOR; (c) the association of having a male cotwin with
      female SOR; and (d) the common and unique genetic causes of temperament and SOR
      symptoms are examined. METHODS: The sample included 1026 twin pairs (mean age = 2
      years 2 months) from a population-based longitudinal study. Auditory and tactile
      SOR symptom domains were partially independent and thus were examined separately.
      RESULTS: Temperamental negative affect and fear were moderately correlated with
      auditory and tactile SOR symptoms. Prenatal complications significantly predicted
      tactile symptoms after controlling for child characteristics. In addition,
      females with a male cotwin showed greater SOR at age 2 years than same-sex female
      dizygotic twins, suggesting a possible risk associated with in utero testosterone
      exposure. Both auditory and tactile SOR domains were heritable. Bivariate genetic
      analyses showed that each SOR domain had a similar genetic relationship with fear
      and negative affect. CONCLUSION: The findings suggest partially nonoverlapping
      causes and risk factors for tactile versus auditory SOR and indicate that
      prenatal factors warrant further investigation.

PMID- 21743352
TI  - In plane sight: a commentary on community inclusion for families affected by
      autism.

PMID- 21743353
TI  - Developmental disabilities grown up: Down syndrome.

PMID- 21743355
TI  - Early skin-to-skin after cesarean to improve breastfeeding.
AB  - This article describes a quality improvement project in which early skin-to-skin
      (STS) contact, in the operating room (OR) and during recovery, was used as an
      intervention to increase the success of breastfeeding initiation among healthy
      infants after cesarean, at a large, urban, acute care teaching hospital. The
      nursing role is key for the intervention, but the program involves the entire
      perinatal team, including the obstetricians, pediatricians, and
      anesthesiologists. During the first 3 months of our intervention, the rate of
      early STS among healthy babies born by cesarean increased from 20% to 68%. The
      rate of infants who did not get STS contact within 4 hours of birth decreased
      from 40% to 9%. Nine months after the initiation of the intervention, 60% of
      healthy cesarean births utilized STS in the OR, and 70% involved STS within 90
      minutes of birth. Healthy infants born by cesarean who experienced STS in the OR
      had lower rates of formula supplementation in the hospital (33%), compared to
      infants who experienced STS within 90 minutes but not in the OR (42%), and those
      who did not experience STS in the first 90 minutes of life (74%). We concluded
      that STS contact was feasible after cesarean and could be provided for healthy
      mothers and infants immediately after cesarean birth. Perinatal and neonatal
      nurses should be leaders in changing practice to incorporate early STS contact
      into routine care after cesarean birth.

PMID- 21743356
TI  - The perinatal safety nurse: exemplar of transformational leadership.
AB  - There is increased attention to the issue of patient safety in the care of
      pregnant women and their infants. The Joint Commission has issued sentinel event
      alerts regarding infant and maternal morbidity and mortality. Hospitals and
      healthcare systems are implementing perinatal patient safety programs to minimize
      the risk of preventable patient harm. This article describes the role of the
      perinatal patient safety nurse as one aspect of a comprehensive initiative to
      promote patient safety for women who give birth. Nurses and organizations
      offering perinatal care are encouraged to incorporate the role of perinatal
      patient safety nurse in their patient safety efforts.

PMID- 21743357
TI  - Repeat radiosurgery for intracranial arteriovenous malformations.
AB  - BACKGROUND: Despite a high success rate in the stereotactic radiosurgical
      treatment of intracranial arteriovenous malformations (AVMs) that cannot be
      safely resected with microsurgery, some patients must be managed after treatment
      failure. OBJECTIVE: To provide an update on the use of repeat linear accelerator
      radiosurgery as a treatment for failed AVM radiosurgery at the University of
      Florida. METHODS: We reviewed 103 patients who underwent repeat radiosurgical
      treatment for residual AVM at the University of Florida between December 1991 and
      December 2007. Each of these patients had at least 2 radiosurgical treatments for
      the same AVM. Patient information, including AVM nidus volume, prescription dose,
      age, and sex, was collected at the time of initial treatment and again at the
      time of retreatment. Patients were followed up after treatment with magnetic
      resonance, computed tomography, and angiographic imaging at standard intervals to
      determine the status of their AVM. The median follow-up after retreatment was 31
      months. RESULTS: Between the first and second treatments, the median AVM nidus
      volume was decreased by 69% (from a median volume of 12.7 to 4.0 cm), allowing
      the median prescribed dose to be increased from 1500 cGy on initial treatment to
      1750 cGy on retreatment. The final obliteration rate on retreatment was 65.3%.
      After salvage retreatment, 5 patients (4.9%) experienced radiation-induced
      complications, and 6 patients (5.8%) experienced posttreatment hemorrhage.
      CONCLUSION: Repeat radiosurgery is a safe and effective salvage treatment for
      AVMs.

PMID- 21743358
TI  - The effect of severing L6 nerve root of the sacral plexus on lower extremity
      function: an experimental study in rhesus monkeys.
AB  - BACKGROUND: Nerve transfer is a valid surgical procedure for lower-extremity
      function restoration after lumbosacral plexus avulsion. OBJECTIVE: To evaluate
      the impact of severing the L6 nerve root on the functions of the healthy limb in
      rhesus monkeys and the feasibility of using the contralateral L6 nerve root as a
      donor nerve to repair lumbosacral plexus root avulsion. METHODS: Twenty-four
      rhesus monkeys were randomly assigned into 2 groups. In the experimental group,
      the right L6 nerve root was explored and severed, whereas in the control group
      animals underwent a sham operation. Electrophysiology, muscle mass, histology,
      and ultrastructure of the target muscles were examined. RESULTS: Three weeks
      after transection, reduced amplitude and prolonged latency of compound muscle
      action potential were observed in the medial gastrocnemius, extensor digitorum
      brevis, peroneus longus, and abductor hallucis muscles of the experimental group,
      as well as reduction in muscle mass and myofiber cross-sectional area of these
      muscles. The number of myelinated nerve fibers of the sciatic nerve in the
      experimental group was significantly less than that of the control group.
      Abnormal ultrastructure of motor end plates of these muscles was also observed in
      the experimental group. Eight weeks postoperatively, all of these parameters were
      similar between the experimental and control groups. CONCLUSION: Severing the L6
      nerve root does not damage the healthy limb as far as electrophysiology, muscle
      mass, histology, and ultrastructure of the target muscles are concerned. L6
      (analogous to S1 in humans) nerve root may be used as a donor nerve to repair
      lumbosacral plexus root avulsion.

PMID- 21743360
TI  - Nurse staffing, hospital operations, care quality, and common sense.

PMID- 21743361
TI  - Singing for unsung heroes.

PMID- 21743362
TI  - Large meningoencephalocele after orbital decompression.
AB  - A 71-year-old woman with a history of thyroid eye disease was seen for evaluation
      of a skull-base mass noted on neuroimaging. She had previously under-gone
      bilateral orbital decompressions and strabismus surgery and had no neurologic
      symptoms. Bony defects along the skull base and cerebrospinal fluid leaks are
      known risks of orbital surgery. This is the first report of a large, asymptomatic
      meningoencephalocele after orbital decompression surgery.

PMID- 21743363
TI  - Trichoblastic fibroma of the eyelid.
AB  - Trichoblastic fibroma (TBF), also known as trichoblastoma, small nodular type, is
      a rare benign cutaneous adnexal tumor that shows trichogenic (follicular)
      differentiation that can be mistaken clinically and histologically for basal cell
      carcinoma (BCC), a locally aggressive trichogenic carcinoma. As the clinical
      behaviors of these two follicular neoplasms are opposite from one another and
      their management is thus different, recognition of TBF is crucial for effective
      therapy. Although TBF most commonly is first seen on the face, this lesion has
      not previously been reported in the eyelid. In this report, we document the first
      case of TBF affecting the ocular adnexa and detail the histologic features that
      differentiate TBF from BCC.

PMID- 21743364
TI  - Orbital hemangiopericytoma/solitary fibrous tumor in childhood.
AB  - A 12-year-old girl had a 6-year history of a large soft-tissue mass in her left
      orbit. The tumor biopsy was previously performed elsewhere when she was 7 years
      old, but no treatment was offered at that time. Later, the tumor was completely
      excised, and histologic examination revealed a mesenchymal neoplasia with typical
      hemangiopericytoma features. At 9 months of follow up, no evidence of local
      recurrence or metastasis was seen.

PMID- 21743365
TI  - Plasmacytoma associated with canaliculitis.
AB  - Plasmacytomas are plasma cell neoplasms that rarely involve ocular adnexal
      tissues as a primary lesion or secondary manifestation of plasma cell myeloma.
      Only one case of plasmacytoma involving the lacrimal drainage system, to our
      knowledge, is described in the literature. The clinical presentation of ocular
      adnexal primary plasmacytoma typically relates to its mass effect. In this
      clinicopathologic report, we describe an unusual presentation of primary
      plasmacytoma of the lacrimal canaliculus as infectious canaliculitis.

PMID- 21743366
TI  - Monocanalicular intubation in external dacryocystorhinostomy.
AB  - PURPOSE: To examine the feasibility of monocanalicular intubation in external
      dacryocystorhinostomy (EX-DCR). METHODS: Monocanalicular intubation using the
      mini-Monoka tube (S1-1500u, FCI Ophthalmics, Marshfield Hills, MA, U.S.A.) was
      performed in 18 patients undergoing EX-DCR. The tube was placed at the superior
      canaliculus in 16 cases and at the inferior canaliculus in 2 cases and was
      removed 3 months postoperatively. All cases were followed for at least 6 months
      postoperatively. RESULTS: The mini-Monoka was well tolerated in all patients. One
      case of spontaneous tube dislocation and 2 cases of presumed tube migration were
      recorded on the 15-day interval. Success rates on the 6-month interval were
      88.88% (16/18), 94.44% (17/18), and 66.66% (12/18), concerning patency upon
      irrigation, resolution of mucopurulent epiphora, and resolution of watery
      epiphora, respectively. CONCLUSIONS: Monocanalicular intubation using mini-Monoka
      in EX-DCR is safe and effective. The technique may have advantages over
      bicanalicular intubation, such as easier insertion and removal, easier probing
      and irrigation though the unintubated canaliculus and, more importantly, less
      risk of punctal or corneal damage.

PMID- 21743367
TI  - Island pedicle and horizontal advancement cheek flaps for medial canthal
      reconstruction.
AB  - PURPOSE: To describe the surgical technique for and results of island pedicle
      cheek flap repair of medial canthal defects. METHODS: We retrospectively reviewed
      the charts of all patients with medial canthal defects repaired with island
      pedicle and horizontal advancement cheek flaps from November 2007 and July 2009.
      Patient demographics, risk factors for poor wound healing, diagnosis, operative
      findings, technique, and postoperative results were reviewed. RESULTS: Twenty
      five patients with a mean age of 61 years underwent reconstruction with island
      pedicle and horizontal cheek flaps. Basal cell carcinoma (88%), squamous cell
      carcinoma (8%), and melanoma in situ (4%) were the indications for surgery. Mohs
      micrographic surgery (76%) and radical excision with controlled margins (24%)
      were the methods of excision. Twenty percent of patients were smokers, 8% had
      diabetes, and 8% were systemically immunosuppressed. Mean defect diameter was 24
      mm, and canalicular involvement was present in 3 cases. LactoSorb anchors were
      necessary for flap fixation in 16% of cases, and additional closure with
      glabellar rotation flaps was used in 20% of cases. Mean follow-up time was 13
      months. Wound dehiscence, mild webbing, and mild ectropion were rare and required
      no secondary revisions. DISCUSSION: The advantages of this technique include a
      well-vascularized pedicle, appropriate volume for filling the defect, and
      inferior support of the island pedicle flap with the horizontal advancement flap.
      The island pedicle cheek flap is a powerful and reliable technique for medial
      canthal defect reconstruction and allows good reconstruction of the natural
      canthal contour with low rates of minor complications.

PMID- 21743368
TI  - Extraintestinal Crohn disease causing bilateral nasolacrimal duct obstruction.
AB  - A 16-year-old boy presented with complaints of epiphora and bilateral palpably
      distended lacrimal sacs. He had a history of Crohn disease involving the small
      and large intestines, and a history of granulomatous cheilitis. Bilateral
      dacryocystorhinostomies were performed through an external approach and revealed
      multiple nodular masses in both lacrimal sacs, which on biopsy, contained
      granulomatous inflammation consistent with extraintestinal Crohn disease. A
      literature search from 1966 to the present using the PubMed database revealed
      three previous publications describing nasolacrimal duct obstruction associated
      with Crohn disease, but these cases did not show pathologic evidence of
      granulomatous inflammation. To our knowledge, this is the first reported case of
      extraintestinal Crohn disease with granulomatous inflammation affecting the
      lacrimal-outflow system.

PMID- 21743369
TI  - Lipoblastomatosis: case report and review of the literature.
AB  - PURPOSE: To describe an unusual presentation of lipoblastomatosis and review the
      existing literature on lipoblastomatosis and lipoblastoma. METHODS: Case report
      and literature review. RESULTS: A 9-year-old girl was originally diagnosed as
      having preseptal cellulitis. After failure of systemic therapy, a CT scan showed
      a mass in the orbit. Biopsy of the lesion confirmed the presence of
      lipoblastomatosis, consisting of immature lipoblasts admixed with more-mature
      adipocytes. CONCLUSIONS: Lipoblastomatosis is a rare benign diffuse lipomatous
      tumor of embryonal fat that is uncommonly found in the head and face of children.

PMID- 21743370
TI  - Endoscopic endonasal retrieval of a nasolacrimal duct stone via the valve of
      Hasner in the inferior meatus.
AB  - A 37 year old man presented with a 6 month history of a right epiphora with
      associated mucus discharge. Lacrimal irrigation demonstrated right unilateral
      partial nasolacrimal duct obstruction, confirmed with lacrimal scintigraphy.
      Nasal endoscopy showed a pale elevation in the right inferior meatus. Endoscopic
      endonasal examination revealed a yellow-white nasolacrimal duct stone emerging
      from the valve of Hasner in the inferior meatus. The distal nasolacrimal duct in
      the lateral wall of the inferior meatus was marsupialised and the stone removed.
      At 12 months follow-up the patient maintained complete resolution of symptoms.

PMID- 21743371
TI  - Conjunctival bleeding after ectropion repair due to paraneoplastic primary
      fibrinolysis.
AB  - In addition to predisposing a patient to hypercoaguability and thrombosis,
      cancers may also cause an antithetical bleeding diathesis through primary
      fibrinolysis. This paraneoplastic pathology has been documented and studied in
      prostate cancer patients for nearly a century but is under-recognized as a
      possible complication of surgery. We report a case of primary fibrinolysis after
      elective ectropion repair in a patient with prostate cancer. Here paraneoplastic
      fibrinolysis produced a delayed postoperative hemorrhage requiring specialized
      therapies, including hospitalization for transfusions of fresh frozen plasma and
      inhibitors of fibrinolysis. Even in the case of an ambulatory and stable cancer
      patient, awareness of this complication and its management can help guide
      surgical decision-making and improve outcomes and follow-up care.

PMID- 21743372
TI  - Human immunodeficiency virus-associated blepharoptosis.
AB  - PURPOSE: To better characterize an unusual blepharoptosis observed in HIV
      positive patients and to evaluate histopathology. METHODS: This retrospective
      case series evaluated patients with HIV/AIDS and blepharoptosis with reduced
      levator excursion. Exclusion criteria included patients with identifiable causes
      of ptosis (e.g., aponeurotic dehiscences, prior eyelid trauma or surgery), known
      myopathic/neuropathic systemic disorders, congenital ptosis, cranial
      neuropathies, and systemic infiltrative processes. RESULTS: All 10 patients had
      bilateral symptomatic blepharoptosis. All patients (100%) were men with a mean
      age at presentation of 54 years (range, 42-77 years). Mean duration of HIV
      infection among 7 of 10 patients was 19 years (range, 13-24 years). Mean (+/-SD)
      MRD1 was 0.7 (+/-0.8) OD and 0.6 (+/-0.8) OS. Mean (+/-SD) levator excursion was
      12 (+/-2.3) OD and 13 (+/-1.8) OS (normal levator excursion >15 mm). No patient
      was taking zidovudine (AZT) at the time of presentation. Nine patients (90%)
      underwent large bilateral levator resections for correction of blepharoptosis.
      Histopathologic specimens revealed abnormal levator muscle fibers with various
      degrees of atrophy, fibrosis, and regeneration without inflammation. CONCLUSIONS:
      The HIV-associated blepharoptosis observed among patients in this study is most
      consistent with a myopathy. Levator muscle histopathologic findings are virtually
      identical to muscle biopsies in individuals with HIV-associated myopathy,
      described before the advent of AZT or highly active antiretroviral therapy
      (HAART). Surgical management with levator resection provides optimal correction
      of HIV-associated blepharoptosis.

PMID- 21743373
TI  - A merkel cell carcinoma of the lacrimal gland.
AB  - Merkel cell carcinoma is a rare neuroendocrine carcinoma that most often arises
      in sun-exposed skin. Primary Merkel cell carcinoma of the lacrimal gland is
      exceedingly rare, with only one prior case reported in the literature. The
      authors present a 49-year-old woman with a 6-month history of painless swelling
      of the left upper eyelid. MRI showed a lacrimal gland mass. Surgical excision was
      performed, and histologic evaluation revealed a Merkel cell carcinoma. Virology
      testing was positive for Merkel cell polyomavirus. The patient was treated with
      local radiation following surgical excision. She has had no recurrence after 1
      year of follow up.

PMID- 21743374
TI  - CYP2D6 polymorphisms and codeine analgesia in postpartum pain management: a pilot
      study.
AB  - BACKGROUND: Codeine, a common opiate prescribed for pain postcesarean section (c
      section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6
      (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies
      of CYP2D6, can biotranform up to 50% more codeine into morphine than normal
      individuals can. In contrast, poor metabolizers (PMs), individuals who have no
      active CYP2D6 genes, convert almost no codeine into morphine and as a result may
      take multiple doses of codeine without attaining analgesia. OBJECTIVE: The aim
      was to study the relationship between CYP2D6 genotype and codeine analgesia among
      women recovering from c-section. METHODS: Forty-five mothers prescribed codeine
      provided a blood sample for CYP2D6 genotyping and recorded their pain level 4
      times a day for 3 days immediately after a c-section. Codeine was used on an as
      needed basis; doses and times were recorded. The relationship between CYP2D6
      genotype, pain scores, need for codeine, and adverse events was studied.
      Theoretical morphine dose, based on CYP2D6 genotype, was estimated. RESULTS:
      Women at the genotypic extremes reported codeine effects consistent with their
      genotype: the 2 PMs of codeine reported no analgesia as a result of taking
      codeine, whereas 2 of the 3 UMs reported immediate pain relief from codeine but
      stopped taking it due to dizziness and constipation. Much larger numbers are
      needed to study similar correlations among extensive and intermediate
      metabolizers. CONCLUSIONS: In this pilot study, the extreme CYP2D6 genotypes (PMs
      and UMs) seemed to predict pain response and adverse events. Larger sample sizes
      are needed to correlate the range of genotypes with pain response.

PMID- 21743375
TI  - Methadone, cocaine, opiates, and metabolite disposition in umbilical cord and
      correlations to maternal methadone dose and neonatal outcomes.
AB  - OBJECTIVES: The purpose was to explore methadone and 2-ethylidene-1,5-dimethyl
      3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with
      maternal methadone dose and neonatal outcomes, and evaluate the window of drug
      detection in umbilical cord of in utero illicit drug exposure. METHODS: Subjects
      comprised 19 opioid-dependent pregnant women from 2 clinical studies, one
      comparing methadone and buprenorphine pharmacotherapy for opioid-dependence
      treatment and the second examining monetary reinforcement schedules to maintain
      drug abstinence. Correlations were calculated for methadone and EDDP umbilical
      cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine-
      and opiate-positive umbilical cord concentrations were compared with those in
      placenta and meconium, and urine specimens collected throughout gestation.
      RESULTS: Significant positive correlations were found for umbilical cord
      methadone concentrations and methadone mean daily dose, mean dose during the
      third trimester, and methadone cumulative daily dose. Umbilical cord EDDP
      concentrations and EDDP/methadone concentration ratios were positively correlated
      to newborn length, peak neonatal abstinence syndrome (NAS) score, and time-to
      peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical
      cord and placenta were positively correlated. Meconium identified many more
      cocaine- and opiate-positive specimens than did umbilical cord. CONCLUSIONS:
      Umbilical cord methadone concentrations were correlated to methadone doses. Also,
      our results indicate that methadone and EDDP concentrations might help to predict
      the NAS severity. Meconium proved to be more suitable than umbilical cord to
      detect in utero exposure to cocaine and opiates; however, umbilical cord could be
      useful when meconium is unavailable due to in utero or delayed expulsion.

PMID- 21743376
TI  - Pharmacodynamic disparities in tacrolimus-treated patients developing cytomegalus
      virus viremia.
AB  - BACKGROUND: The optimal balance between efficacy and toxicity of tacrolimus (Tac)
      treatment remains unsolved. The quantification of nuclear factor of activated T
      cell (NFAT)-regulated gene expression may provide a tool to monitor the
      individual susceptibility to Tac. METHODS: Expression of NFAT-regulated genes
      (interleukin-2, interferon-gamma, and granulocyte-macrophage colony stimulating
      factor) in peripheral blood from renal transplant patients (N = 73) was measured
      by quantitative real-time polymerase chain reaction (at C0, C1.5, and C4) and
      correlated to clinical endpoints in a 1-year observation period. In a subgroup (n
      = 10), NFAT expression was quantified over a 12-hour dose interval. RESULTS:
      Median daily Tac dose of 73 stable renal transplant patients [median age 47 years
      (range 19-69 years)] was 5 mg (1-13), Tac trough (C0), 1.5-hour (C1.5) and 4-hour
      (C4) concentrations were 8.5 mcg/L (3-20), 20 mcg/L (4.7-50.4), and 14.5 mcg/L
      (4.5-37.5), respectively. The mean residual expression of all 3 NFAT-regulated
      genes was 21% at C1.5 (1-84) and 35% at C4 (2-88). The relative reduction of gene
      transcripts was inversely correlated with the individual Tac blood
      concentrations. Seven patients had cytomegalus virus viremia during the
      observation period, and their residual NFAT-regulated gene expression at C1.5 was
      significantly lower [13% (1-21) versus 26% (1-84), P = 0.02] compared with those
      without viremia despite comparable Tac blood concentrations (6.3 versus 8.6
      mcg/L). CONCLUSIONS: Monitoring of NFAT-regulated gene expression in Tac-treated
      transplant recipients provides a tool to assess the individual response to Tac,
      identify patients at the risk of developing cytomegalus virus viremia, and may,
      thus, help to select the optimal Tac dose with respect to safety and toxicity.

PMID- 21743377
TI  - Evaluation of the Abbott ARCHITECT i2000 sirolimus assay and comparison with the
      Abbott IMx sirolimus assay and an established liquid chromatography-tandem mass
      spectrometry method.
AB  - BACKGROUND: Sirolimus is indicated for prophylaxis treatment to prevent solid
      organ rejection. Due to intrapatient and interpatient variabilities in
      pharmacokinetics, risk of concentration-related toxicity, risk of noncompliance,
      and a high likelihood of drug-drug interactions, therapeutic drug monitoring of
      sirolimus is essential. There are several methodologies used clinically to
      monitor sirolimus, ranging from immunoassay to tandem mass spectrometry, each
      with potential strengths and limitations. The purpose of our study was to
      validate the Abbott ARCHITECT i2000 sirolimus assay. MATERIALS AND METHODS: The
      Abbott ARCHITECT i2000 sirolimus assay was evaluated for linearity, limit of
      detection, limit of quantification, imprecision, common interferences, and
      accuracy. Accuracy was compared with the Abbott IMx sirolimus assay and with an
      established liquid chromatography-tandem mass spectrometry method. Stability of
      sirolimus when specimens were stored frozen (-20 degrees C) or refrigerated (2-8
      degrees C) and degree of crossreactivity of the i2000 with everolimus were also
      evaluated. RESULTS: The ARCHITECT i2000 assay demonstrated good linearity, low
      imprecision, and was free of common interferences. Results for both immunoassay
      methods were biased slightly high, compared with those of liquid chromatography
      tandem mass spectrometry. Sirolimus was stable when samples were stored either
      refrigerated or frozen. However, the results generated with samples stored
      refrigerated had an increase in scatter on the regression plots compared with
      those generated for samples that were stored frozen, indicating that extraction
      of the drug may be incomplete, particularly with the Abbott IMx assay. In
      addition, statistical performance indices suggest that the agreement between the
      ARCHITECT i2000 and Abbott IMx was better for frozen patient samples. The
      ARCHITECT i2000 and the Abbott IMx methods both exhibited a >100% crossreactivity
      with everolimus. CONCLUSIONS: The Abbott ARCHITECT i2000 instrument demonstrates
      reasonable sensitivity, precision, and accuracy for supporting routine
      therapeutic drug monitoring of sirolimus with either refrigerated or frozen whole
      blood collected from patients who are not comedicated with everolimus.

PMID- 21743378
TI  - Therapeutic drug monitoring of clomipramine and amitriptyline in a depressed
      patient with upper digestive tract resection.
AB  - We describe a 55-year-old woman with extensive digestive resection and recurrent
      depressive disorder resistant to oral clomipramine tablets but not to an oral
      solution of amitriptyline. In the light of this case report, the potential
      mechanisms of drug resistance after digestive resection are discussed, including
      the importance of drug monitoring.

PMID- 21743379
TI  - CYP3A5, ABCB1, and SLCO1B1 polymorphisms and pharmacokinetics and virologic
      outcome of lopinavir/ritonavir in HIV-infected children.
AB  - OBJECTIVE: CYP3A5, MDR1 (ABCB1), and OATP1 (SLCO1B1) polymorphisms have been
      associated with variability in the pharmacokinetics (PK) of protease inhibitors.
      The aim of this study was to investigate the influence of CYP3A5 A6986G, ABCB1
      (C3435T and G2677T), and SLCO1B1 (T521C and A388AG) polymorphisms on the PK and
      virologic outcome of lopinavir/ritonavir (LPV/RTV) in HIV-infected children.
      DESIGN AND METHODS: We conducted a prospective cohort study in children (4-18
      years old) on stable antiretroviral therapy with LPV/RTV. CYP3A5, ABCB1, and
      SLCO1B1 genotypes were determined using polymerase chain reaction amplification
      with allelic discrimination assays. The 12-hour plasma area under the
      concentration-time curves (AUC) and clearances (CL) of LPV and RTV were estimated
      using noncompartmental models. HIV RNA viral load was evaluated every 12 weeks
      for a total study period of 52 weeks. Analysis of covariance models with
      adjustment for age and adherence and allometric adjustment of CL were used to
      assess associations between studied polymorphisms and AUC, CL, and HIV RNA.
      RESULTS: Fifty children (median age 11.2 years) were enrolled. Allele frequencies
      of the genotypes studied were in Hardy-Weinberg equilibrium. There was no
      statistically significant association between LPV or RTV AUC or CL, and CYP3A5,
      ABCB1, or SLCO1B1 A388G polymorphisms. There was a significant association
      between SLCO1B1 T521C genotype and increased LPV AUC (P = 0.042) and a nearly
      significant association with decreased LPV CL (P = 0.063). None of the studied
      polymorphisms, including SLCO1B1 T521C, were associated with virologic outcome
      during 52 weeks of study follow-up. CONCLUSIONS: There was no statistically
      significant influence of the CYP3A5, ABCB1, or SLCO1B1 A388AG polymorphisms on
      the PK and virologic outcome of LPV/RTV in HIV-infected children. SLCO1B1 T521C
      polymorphism was significantly associated with an increase in LPV AUC but was not
      associated with undetectable HIV RNA during the study period.

PMID- 21743380
TI  - Therapeutic drug monitoring of infliximab in spondyloarthritis: an observational
      open-label study.
AB  - BACKGROUND: Infliximab is a chimeric monoclonal antibody that binds to human
      tumor necrosis factor alpha and which is approved for refractory
      spondyloarthritis (SpA). Individual adjustment of infliximab dosage may help to
      improve the therapeutic response in SpA. We investigated whether a knowledge of
      infliximab serum concentration modifies physician decision and improves the
      control of disease activity in SpA. METHODS: Thirty-two patients routinely
      treated with infliximab were included in an observational open-label study. On
      visit 1 (V1), according to disease activity, a preliminary therapeutic decision
      was selected among 4 therapeutic options (ie, decrease, increase, maintain the
      dosage of infliximab, or switch over for another treatment), and a blood sample
      was collected to measure infliximab trough serum concentration. The final
      therapeutic decision, based on both disease activity and infliximab serum
      concentration assessed at V1, was applied at the following infusion (V2).
      Clinical and biological evaluations were performed at V3 and V4 and compared with
      those at V1. RESULTS: The measurement of infliximab trough concentration modified
      the therapeutic decision for 10 patients (31%). For both patients with increased
      or decreased infliximab dosage at V2, median Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI) was similar at V3 or V4 as compared with that at V1.
      However, a trend for an inverse relationship between infliximab serum
      concentrations and BASDAI was observed. CONCLUSIONS: Knowledge of infliximab
      trough concentration modified the therapeutic decision for SpA patients with
      predominantly axial symptoms but did not improve the control of disease activity
      as estimated by the BASDAI.

PMID- 21743381
TI  - Bleeding incidence with concomitant use of antidepressants and warfarin.
AB  - INTRODUCTION: Bleeding is the major complication associated with warfarin
      therapy. Some antidepressants are also associated with increased bleeding risk.
      Warfarin and antidepressants are used frequently in combination, but it is
      unclear whether concomitant use increases the risk of bleeding beyond that with
      warfarin alone. The primary goal of this study was to determine whether the use
      of warfarin and an antidepressant increases the risk for bleeding outcomes
      compared with the use of warfarin alone. The secondary goal was to characterize
      the risk of bleeding in warfarin-treated patients taking one specific class of
      antidepressant, selective serotonin reuptake inhibitors (SSRIs). MATERIALS AND
      METHODS: This was a retrospective, single-center, study of warfarin-treated
      patients prescribed (n = 46) and not prescribed (n = 54) an antidepressant.
      Medical records over 6 months were reviewed for international normalized ratio
      values, medical history, bleeding type and incidence, and hospitalization due to
      bleeding. Patients were included in the antidepressant group if they were taking
      concomitant warfarin and antidepressant therapy consistently for a period of 6
      months and in the control group if they were not taking an antidepressant with
      warfarin. RESULTS: The use of any antidepressant with warfarin was not associated
      with the incidence of any bleeding or major bleeding during the 6-month period.
      However, the use of an SSRI with warfarin was associated with an increase in any
      bleeding event (odds ratio 2.6, 95% confidence interval, 1.01-6.4 P = 0.04). The
      use of an SSRI remained a significant predictor of bleeding after accounting for
      other factors associated with bleeding risk. CONCLUSIONS: Based on these data, it
      is important to clarify the interaction between warfarin and SSRIs in regard to
      bleeding risk given the high frequency of their concomitant use.

PMID- 21743382
TI  - Therapeutic drug monitoring of voriconazole after intravenous administration in
      infants and children with primary immunodeficiency.
AB  - OBJECTIVE: A voriconazole trough concentration (Ctrough) <1 mg/L is associated
      with a higher risk of treatment failure. The aim of this work was to describe the
      probability of not achieving this target concentration in infants and children
      receiving intravenous voriconazole. METHODS: Voriconazole trough concentrations
      obtained during routine therapeutic drug monitoring over a 5-year period were
      collected retrospectively from infants and children receiving intravenous
      voriconazole for presumed or proven invasive fungal infections. RESULTS: Sixty
      two trough concentrations were obtained from 6 infants and 10 children. The risk
      of a Ctrough <1 mg/L was 77% and 47%, respectively. Daily doses between 20 and 32
      mg/kg were necessary in some patients to achieve a Ctrough >1 mg/L, compared with
      the currently recommended 14-mg/kg regimen. CONCLUSIONS: Routine therapeutic drug
      monitoring is potentially helpful in infants and children receiving voriconazole,
      even intravenously.

PMID- 21743383
TI  - Quantification of 6 glucocorticoids in human plasma by liquid chromatography
      tandem mass spectrometry: method development, validation, and assessment of
      matrix effects.
AB  - BACKGROUND: Glucocorticoids are a group of steroid hormones with
      immunosuppressive and anti-inflammatory properties. In this article, we report
      the development and the validation of a liquid chromatography tandem mass
      spectrometry method for the simultaneous quantification of prednisolone,
      prednisone, cortisol, cortisone, methylprednisolone, and dexamethasone in human
      plasma. Furthermore, matrix effects were assessed qualitatively and
      quantitatively. METHODS: Plasma protein precipitation was performed with
      acetonitrile containing internal standards. Liquid-liquid extraction with
      dichloromethane and evaporation were used for cleanup and enrichment. The
      glucocorticoids were analyzed using reversed-phase chromatography and multiple
      reaction monitoring of positive ions. RESULTS: The mean extraction recovery was
      in the range 66.5%-104.8%, whereas the lower limits of quantification ranged from
      1.5 to 4.0 MUg/L. The intraday and interday accuracies of all the analytes were
      within 89.4%-116.6%, and imprecision was <15.6%. Ion suppression ranged from
      15.3% to 27.3%. However, the matrix effects did not compromise the assay
      performance, with mean deviations in calculated concentrations of -4.8% to 2.1%
      between methanol and matrix. Short-term stability was acceptable for 5 of the
      analytes, with deviations from baseline between -3.4% and 8.7% after 24 hours at
      4 degrees C, although methylprednisolone was stable for 6 hours with a
      degradation of 10.2%. Deviations from baseline in controls stored at -20 degrees
      C for 6 months ranged from -22.3% to 6.3%. All analytes were stable after 3
      repetitive freeze-thaw cycles, with a maximum degradation of 5.5%. In terms of
      postpreparative stability, the analytes were stable after 24 and 48 hours at 4
      degrees C, with maximum degradation of 6.1% and 9.4%, respectively. CONCLUSIONS:
      A validated, sensitive, selective, and reproducible method for quantifying the
      concentrations of 6 glucocorticoids in human plasma by liquid chromatography
      tandem mass spectrometry is reported.

PMID- 21743384
TI  - Drug use and screening in pediatric trauma.
AB  - BACKGROUND: There is a paucity of research on substance use in the pediatric
      trauma population. This study aims to describe trends in substance use and
      screening in the Canadian pediatric trauma population. MATERIALS AND METHODS: A
      retrospective review of the London Health Sciences Centre trauma database from
      April 1999 to January 2009 identified patients less than 18 years old admitted
      after major trauma [injury severity score (ISS) > 12]. Data extracted included
      age, gender, ISS, blood alcohol concentration (BAC), and results of toxicology
      screens. RESULTS: BAC data were available for 799 patients and toxicology screens
      for 761 patients. BAC testing was completed in 30% (21% positive). Toxicology
      screens were completed in 7% (44% positive). Increasing age was associated with
      screening for alcohol (odds ratio = 1.4; 95% confidence interval 1.3-1.5).
      Screening for drug use had a bimodal distribution, with no children aged 4-10
      years screened. Those screened for drugs and alcohol had a significantly higher
      ISS than those not tested (BAC 28 versus 23, P < 0.001, toxin screening 29 versus
      24, P = 0.003). The most common ingestions were alcohol, benzodiazepines,
      cannabinoids, and opiates. CONCLUSIONS: Screening for drugs and alcohol is
      sporadic in the pediatric trauma population. Further study utilizing a universal
      approach to drug and alcohol screening is needed to further delineate the true
      prevalence of substance use in this population.

PMID- 21743385
TI  - Evaluation of performance of new, isotopically labeled internal standard
      ([13c2d4]RAD001) for everolimus using a novel high-performance liquid
      chromatography tandem mass spectrometry method.
AB  - INTRODUCTION: Everolimus was approved for the prevention of organ rejection of
      kidney transplants in adult patients in April 2010 by the US Food and Drug
      Administration. Therapeutic drug monitoring of everolimus is recommended for all
      patients receiving this immunosuppressant. The goal of this study was to improve
      and revalidate our previously published high-performance liquid chromatography
      tandem mass spectrometry method for the measurement of everolimus and to assess
      the performance of the recently introduced isotopically labeled internal standard
      (IS). METHOD: For this method, the following innovative changes were
      incorporated: (1) sample preparation includes the addition of water to hemolyze
      red blood cells; (2) a separate extraction column is added to the system; (3)
      different settings of the switching valve are used to minimize dead volume; (4) a
      more sensitive mass spectrometer is used (API 5000) for drug detection; (5)
      isotopically labeled everolimus is used as the IS. RESULTS: The addition of water
      to blood before adding ZnSO4 with methanol improves absolute recovery of
      everolimus from 77.3% +/- 6.18% to 82.3% +/- 6.3%. The use of the more sensitive
      mass spectrometer permitted the use of a smaller sample volume and lowered the
      lower limit of quantification from 1.0 to 0.5 ng/mL. Between-day precision for
      quality control samples is below 9%, and the accuracy ranged from 94.8% to
      106.4%. Neither carryover nor matrix effects were observed. A comparison study
      showed very good agreement between the results obtained by our laboratory and
      those obtained by a reference laboratory (r = 0.93). The performance of the new
      IS, [13c2d4] RAD001, was compared with that of SDZ RAD 223-756. Everolimus
      concentration results obtained using the isotopically labeled IS agreed more
      closely with the results from the reference laboratory (using 13c2d4) as compared
      with everolimus concentration results obtained using the analog (SDZ RAD 223
      756). CONCLUSIONS: This revised methodology together with the comparison study
      data proved that our novel method for the measurement of everolimus is sensitive,
      precise, reliable, and robust.

PMID- 21743386
TI  - Limited sampling strategies for monitoring tacrolimus in pediatric liver
      transplant recipients.
AB  - OBJECTIVE: To develop and validate limited sampling strategies (LSSs) for
      tacrolimus in pediatric liver transplant recipients. METHODS: Thirty-six 12-hour
      pharmacokinetic profiles from 28 pediatric liver transplant recipients (0.4-18.5
      years) were collected. Tacrolimus concentrations were measured by immunoassay and
      area under the curve (AUC0-12) was determined by trapezoidal rule. LSSs
      consisting of 1, 2, 3, or 4 concentration-time points were developed using
      multiple regression analysis. Eight promising models (2 per category) were
      selected based on the following criteria: r2 >= 0.90, inclusion of trough
      concentration (C0), and time points within 4 hours postdose. The predictive
      performance of these LSSs was evaluated in an independent set of data by
      measuring the mean prediction error and the root mean squared prediction error.
      RESULTS: Five models including 2-4 time points predicted AUC0-12 with a +/-15%
      error limit. Bias (mean prediction error) and precision (root mean squared
      prediction error) of LSS involving C0, C1, and C4 (AUCpredicted = 9.30 + 3.69 *
      C0 + 2.19 * C1 + 4.69 * C4) were -4.98% and 8.29%, respectively. Among single
      time point LSSs, the model using C0 had a poor correlation with AUC0-12 (r2 =
      0.53), whereas the one with C4 had the highest correlation with tacrolimus
      exposure (r2 = 0.84). CONCLUSIONS: Trough concentration is a poor predictor of
      tacrolimus AUC0-12 in pediatric liver transplant recipients. However, LSSs using
      2-4 concentration-time points obtained within 4 hours postdose provide a reliable
      and convenient method to predict tacrolimus exposure in this population. The
      proposed LSSs represent an important step that will allow the undertaking of
      prospective trials aiming to better define tacrolimus target AUC in pediatric
      liver transplant recipients and to determine whether AUC-guided monitoring is
      superior to C0-based monitoring in terms of efficacy and safety.

PMID- 21743387
TI  - Deleterious impact of mismatching for human leukocyte antigen-C in presensitized
      recipients of kidney transplants.
AB  - BACKGROUND: Allocation of deceased donor kidneys is commonly based on matching
      for human leukocyte antigen (HLA)-A, -B, and -DR, whereas HLA-C is currently
      disregarded. We investigated the influence of HLA-C compatibility on renal
      allograft survival. In addition, we tested an approach of matching for HLA-C
      epitopes. METHODS: A cohort of 2260 deceased donor kidney transplants were typed
      for HLA-C using polymerase chain reaction-sequence specific primer method.
      Samples for DNA typing, serum results on presensitization (lymphocytotoxicity),
      and clinical data were provided by transplant centers participating in the
      Collaborative Transplant Study. RESULTS: HLA-C mismatch was found to be
      associated with significantly decreased graft survival in presensitized (P<0.001)
      but not in non-presensitized (P=0.75) recipients. Mismatch of certain HLA-C
      epitopes seemed to be more influential than others, with mismatches showing a
      negative impact on graft survival in presensitized patients. CONCLUSIONS: HLA-C
      mismatch has a substantial deleterious effect on graft survival in presensitized
      kidney recipients. Our study points out the need for investigations directed at
      identifying donor-specific HLA-C antibodies and evaluating their relevance in
      transplantation. In view of the fact that current assays for determining HLA-C
      specific antibodies are hampered by additional detection of clinically irrelevant
      antibodies, matching for HLA-C may provide a reasonable approach to improve
      transplant outcomes in presensitized kidney transplant recipients.

PMID- 21743388
TI  - Synthesis and spectroscopic characterization of two tetrasubstituted cationic
      porphyrin derivatives.
AB  - An imidazolium tetrasubstituted cationic porphyrin derivative (the free base and
      its Zn(II) complex) with five-membered heterocyclic groups in the meso-positions
      were synthesized using microwave irradiation, and the compounds obtained
      characterized by (1)H-NMR and mass spectrometry. We observed that under microwave
      irradiation the yield is similar to when the synthesis is performed under
      conventional heating, however, the time required to prepare the porphyrins
      decreases enormously. In order to investigate the electronic state of these
      compounds, we employed UV-Vis and fluorescence spectroscopy combined with quantum
      chemical calculations. The results reveal the presence, in both compounds, of a
      large number of electronic states involving the association between the Soret and
      a blue-shifted band. The Soret band in both compounds also shows a considerable
      solvent dependence. As for emission, these compounds present low quantum yield at
      room temperature and no solvent influence on the fluorescence spectra was
      observed.

PMID- 21743389
TI  - Characterization and determination of the alkaloid metabolites of Evodiae fructus
      in rat urine by liquid chromatography-tandem mass spectrometry detection.
AB  - The lack of authentic standards limits the quantitative analysis of herbal drugs
      in biological samples. This present work demonstrated a practicable assay of
      herbs and their metabolites independent of the availability of authentic
      standards. A liquid chromatography-electrospray ionization-mass spectrometry (LC
      ESI-MS) method for the qualitative and quantitative determination of the
      metabolites after oral administration of Evodiae fructus and Zuojinwan
      preparation in rat urine has been developed. Urine samples extracted with a
      protein precipitation procedure were separated on a C(18) column using a mixture
      of water (containing 0.1% formic acid) and acetonitrile (30:70, v/v) as mobile
      phase. The detection was performed by MS with electrospray ionization interface
      in positive selected reaction monitoring (SRM) mode. One urine sample after
      administration was selected as 'standard'. The method validation was carried out
      according to a conventional method that was calibrated by authentic standards.
      The fully validated method was applied to the pharmacokinetic study of the
      metabolites in rat urine. The results could provide evidence to explain the
      combination of Coptidis rhizoma and Evodiae fructus in terms of elimination.

PMID- 21743390
TI  - Factors related to late stage diagnosis of oral squamous cell carcinoma.
AB  - AIMS: To identify factors related to advanced-stage diagnosis of oral cancer to
      disclose high-risk groups and facilitate early detection strategies. STUDY
      DESIGN: An ambispective cohort study on 88 consecutive patients treated from
      January 1998 to December 2003. INCLUSION CRITERIA: pathological diagnosis of OSCC
      (primary tumour) at any oral site and suffering from a tumour at any TNM stage.
      Variables considered: age, gender, smoking history, alcohol usage, tumour site,
      macroscopic pattern of the lesion, co-existing precancerous lesion, degree of
      differentiation, diagnostic delay and TNM stage. RESULTS: A total of 88 patients
      (mean age 60+/-11.3; 65.9% males) entered the study. Most patients (54.5%)
      suffered no delayed diagnosis and 45.5% of the carcinomas were diagnosed at early
      stages (I-II). The most frequent clinical lesions were ulcers (70.5%). Most cases
      were well- and moderately-differentiated (91%). Univariate analyses revealed
      strong associations between advanced stages and moderate-poor differentiation
      (OR=4.2; 95%CI=1.6-10.9) or tumour site (floor of the mouth (OR=3.6; 95%CI=1.2
      11.1); gingivae (OR=8.8; 95%CI=2.0-38.2); and retromolar trigone (OR=8.8;
      95%CI=1.5-49.1)). Regression analysis recognised the site of the tumour and the
      degree of differentiation as significantly associated to high risk of late-stage
      diagnosis. CONCLUSIONS: Screening programmes designed to detect asymptomatic oral
      cancers should be prioritized. Educational interventions on the population and on
      the professionals should include a sound knowledge of the disease presentation,
      specifically on sites like floor of the mouth, gingivae and retromolar trigone.
      More studies are needed in order to analyse the part of tumour biology on the
      extension of the disease at the time of diagnosis.

PMID- 21743391
TI  - Ultramorphology and dentine permeability changes induced by prophylactic
      procedures on exposed dentinal tubules in middle dentine.
AB  - OBJECTIVES: The purpose of this study was to evaluate the changes in dentinal
      permeability (i.e. hydraulic conductance) after prophylactic treatment performed
      using prophy-powders with air-polishing system or prophy-pastes applied on
      exposed middle dentine. The changes in dentine morphology were evaluate by SEM.
      STUDY DESIGN: Several prophylactic pastes or air-polishing powders were tested in
      this study. Dentine discs from human third molars were used to study the
      quantitative reduction of the dentine permeability under simulated pulpal
      pressure (20 cm H2O). Further specimens were gold-coated and observed with the
      use of a SEM. RESULTS: The results of this study showed different reductions of
      dentin permeability effects based on the type of product employed (i.e.
      prophylactic paste or air-polishing powders). The use of Sylc bioactive glass and
      sodium bicarbonate were the most effective in reducing dentine permeability of
      the specimens etched with the phosphoric. The air-polishing procedures performed
      with Sylc bioactive glass created a dentine surface devoid of exposed dentinal
      tubules due to the presence of a compact multilayered smear layer. Colgate
      Sensitive Pro-Relief and Nupro NU-Solution reduced the dentine permeability up to
      69.8% and 66.9% respectively. CONCLUSION: Although all the tested products are
      able to statistically reduce dentine permeability, Sylc bioactive glass is an
      innovative and effective product suitable for the reducing of the dentine
      permeability during prophylactic procedures of air-polishing.

PMID- 21743392
TI  - Diagonal ear lobe crease and atherosclerosis: a review of the medical literature
      and dental implications.
AB  - In Spain a significant number of individuals die from atherosclerotic disease of
      the coronary and carotid arteries without having classic risk factors and
      prodomal symptoms.  The diagonal ear lobe crease (DELC) has been characterized in
      the medical literature as a surrogate marker which can identify high risk
      patients having occult atherosclerosis.  This topic however has not been examined
      in either the medical or dental literature emanating from Spain. The majority of
      clinical, angiography and postmortem reports support the premise that DELC is a
      valuable extravascular physical sign able to distinguish some patients at risk of
      succumbing to atherosclerosis of the coronary arteries.  A minority of studies
      have however failed to support this hypothesis.  More recently reports using B
      mode ultrasound have also linked DELC to atherosclerosis of the carotid artery
      and another report has related DELC to the presence of calcified carotid artery
      atheromas on panoramic radiographs. DELC is readily visible during head and neck
      cancer screening examinations.  In conjunction with the patient's medical
      history, vital signs, and panoramic radiograph, the DELC may assist in
      atherosclerotic risk.

PMID- 21743393
TI  - Variations in teaching of removable partial dentures in Spanish dental schools.
AB  - OBJECTIVES: Despite the increasing demand for implant-based treatments, removable
      partial dentures (RPDs) are frequently used in the oral rehabilitation of
      partially dentate patients. Furthermore, the Bologna Declaration Agreement (1999)
      promotes the freedom of movement both of students among dental schools and of
      graduates across the European Union (EU). Given that inconsistency in teaching
      among dental schools may lead to confusion, this study aimed to evaluate the
      status of teaching and clinical experience reached by undergraduate dental
      students in Spanish dental schools in relation to RPDs. STUDY DESIGN: A
      questionnaire seeking information on the preclinical and clinical teaching of
      RPDs was emailed to all Spanish dental schools (11 public, 4 private) with
      complete undergraduate degree dental programmes in November 2009. Descriptive
      statistical data analysis was performed. RESULTS: A 100% response rate was
      obtained. The average duration of the preclinical course in Spain was 44 hours
      (38 hours in the public schools and 60.5 hours in the private schools). However,
      public schools reported a greater number of RPDs made per student prior to
      graduation, with an average of 3.4 acrylic (range: 1-20) and 3.4 cobaltchromium
      (range: 1-20) RPDs. The corresponding means for private schools were 1 acrylic
      (range: 0-2) and 2.3 cobalt-chromium (range: 1-4). One public school (9%) stated
      that they were teaching RPDs using Problem-Based- Learning. CONCLUSIONS: Similar
      to that noted in previously surveyed countries, variations in teaching programmes
      and clinical experience concerning RPDs achieved by Spanish dental students were
      evident. While diversity of teaching is often considered to be of benefit, dental
      students must be adequately trained to ensure that they meet the needs of the
      patients they will serve during their careers.

PMID- 21743394
TI  - Discriminant ability for caries risk of modified colorimetric tests.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between the
      caries risk in children over a two-year period and their baseline caries status,
      salivary levels of mutans streptococci and lactobacilli, and results of the Alban
      test and modifications thereof using different substrates. STUDY DESIGN: Ninety
      five children aged 6-7 were examined in Granada (southern Spain) for dental
      caries at baseline and every six months. Stimulated saliva was sampled and
      inoculated in 7 colorimetric tests based on Snyder's medium with different sugars
      and polyalcohols. A mutans streptococci and lactobacilli count was performed
      (Dentocult SM strip(r) and Dentocult LB(r)). Caries risk proportions were
      contrasted against the potential predictor variables, i.e., basal caries history
      and salivary tests, by means of the Mantel Haenszel test for linear association,
      based on a chi-square distribution with 1 degree of freedom (df). RESULTS: Caries
      index, lactobacillus count and colorimetric tests showed significant, but
      limited, and non-different discriminant abilities. Increasing values of all
      predictor variables, except for Dentocult SM(r), were related to increasing
      caries risk proportions. CONCLUSION: Colorimetric test results and caries history
      showed similar correlation values as caries predictors.

PMID- 21743395
TI  - TWIST and p-Akt immunoexpression in normal oral epithelium, oral dysplasia and in
      oral squamous cell carcinoma.
AB  - OBJECTIVES: The aim of this study was to evaluate the immunoexpression of TWIST
      and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma
      (OSCC), correlating their expressions with the histological features of the
      lesions. STUDY DESIGN: Immunohistochemical studies were carried out on 10 normal
      oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue
      samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on
      the specimens and the positivity of the reactions was calculated for 1000
      epithelial cells. RESULTS: Kruskal-Wallis and Dunn's post tests revealed a
      significant difference in TWIST and p- Akt immunoexpression among normal oral
      mucosa, OL and OSCC. In addition, a significant positive correlation was found
      between TWIST and p-Akt expressions according to the Pearson's correlation test.
      CONCLUSIONS: The results obtained in the current study suggest that TWIST and p
      Akt may participate of the multi-step process of oral carcinogenesis since its
      early stages.

PMID- 21743396
TI  - Survival of occlusal ART restorations in primary molars placed in school
      environment and hospital dental setup-one year follow-up study.
AB  - OBJECTIVE: The objectives of this clinical study were to: evaluate the survival
      of occlusal atraumatic restorative treatment (ART) restorations, on a
      longitudinal basis, in the primary molars of children; and compare the success
      rate of ART restorations placed in school environment and in hospital dental
      setup. STUDY DESIGN: One dentist placed 120 ART restorations in 60 five- to seven
      year-olds who had bilateral matched pairs of carious primary molars. A split
      mouth design was used to place restorations in school and in hospital dental
      setup, which were assigned randomly to contralateral sides. Restorations were
      evaluated after 6 and 12 months using the ART criteria. RESULTS: The survival
      rate of ART restorations placed in school environment was 82.2% at the 6-month
      assessment and 77.77% at the 12-month assessment. The success rates of ART
      restorations placed in hospital dental setup in the 2 assessments were 87.7% and
      81.48%, respectively. There was no statistically significant difference between
      the ART restorations placed in school environment and hospital dental setup in
      both assessments (P > O.05). The main cause of failure was the loss of
      restoration. CONCLUSIONS: The one year success rate of occlusal ART restorations
      in primary molars was moderately successful. The ART technique's done in hospital
      dental setup was not proven to be better than restorations placed in school
      environment.

PMID- 21743397
TI  - Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor
      alpha in patients with leukoplakia and oral cancer.
AB  - OBJECTIVES: The aim of study was to compare salivary and serum concentrations of
      interleukin 1 beta (IL-1beta), interleukin 6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) in patients with oral leukoplakia, oral cancer and healthy
      controls. STUDY DESIGN: Eighty eight patients (28 with oral cancer, 29
      leukoplakia, and 31 healthy controls) were included in this study. Cytokine
      concentrations were measured by commercial enzyme linked immunoassay. RESULTS:
      Salivary IL-1beta and IL-6 were significantly higher in oral cancer patients than
      in patients with leukoplakia and control group (p<0.05). No differences in
      concentrations of salivary TNF-alpha between either of the groups were observed.
      Serum concentrations of IL-1beta were below level of detection in all but two
      participants. No significant differences between the groups were observed in
      serum concentrations of IL-6. Serum TNF-alpha was significantly higher in control
      subjects than in oral cancer patients. CONCLUSIONS: Patients with oral cancer
      have elevated levels of inflammatory cytokines in their saliva. Whether this
      elevation can be used for monitoring the malignant transformation of oral
      leukoplakia remains to be answered by further follow up studies.

PMID- 21743398
TI  - Complications associated with the ball, bar and Locator attachments  for implant
      supported overdentures.
AB  - BACKGROUND: The purpose of this clinical study was to evaluate the complications
      associated with the different attachments used in implant-supported overdentures,
      including prosthetic problems and implant failures. A comparison of ball, bar and
      Locator (Zest Anchors, Inc, homepage, Escondido, CA, USA) attachments, in
      completely edentulous patients with two, three or four implants, was conducted.
      MATERIAL AND METHODS: A total of 36 edentulous patients (20 female, 16 male) with
      a mean age of 66.3 years, were enrolled in the study. The patients were treated
      with 95 implants, for the prosthetic restoration of the maxilla or the mandible.
      The mean follow-up time was 41.17 months. Prosthetic complications including,
      fractured overdentures, replacements of O-ring attachment and retention clips,
      implant failures, hygiene problems, mucosal enlargements, attachment fractures,
      retention loss and dislodgement of the attachments were recorded and evaluated.
      The recall visits at 3, 6, 12 months and, annually thereafter. RESULTS: Fourteen
      complications in the ballattachment group and 7 complications in the bar group
      were observed. No complications were observed in the locator group. The
      difference was found to be as statistically significant (p=0,009). Six of the 95
      implants had failed. Totally 39 implant overdentures were applied. Three
      prostheses were renewed because of fractures. CONCLUSION: Within the limits of
      the present study, it was concluded that the locator system showed superior
      clinical results than the ball and the bar attachments, with regard to the rate
      of prosthodontic complications and the maintenance of the oral function.

PMID- 21743399
TI  - Microleakage comparison of glass-ionomer and white mineral trioxide aggregate
      used as a coronal barrier in nonvital bleaching.
AB  - OBJECTIVES: There is some evidence that the pH at the root surface is reduced by
      intracoronal placement of bleaching pastes, which is known to enhance
      osteoclastic activity. Therefore, it is recommended that a protective barrier be
      used over the canal filling to prevent leakage of bleaching agents. Glass-ionomer
      (GI) is commonly used as a coronal barrier before nonvital bleaching. Because
      mineral trioxide aggregate (MTA) creates high alkalinity after mixing with water,
      using MTA as a protective barrier over the canal filling may not only prevent
      leakage of bleaching agents and microorganisms, but may prevent cervical
      resorption. The aim of this study was to evaluate sealing ability of white
      mineral trioxide aggregate (WMTA) as a coronal barrier before nonvital bleaching.
      STUDY DESIGN: Root canals of one hundred thirty human maxillary incisors were
      instrumented and filled with gutta-percha without sealer. Gutta-percha was
      removed up to 3 mm below the cementoenamel junction (CEJ). The teeth were
      randomly divided into six experimental groups of 20 teeth each and two control
      groups of 5. In three experimental groups, WMTA was packed into the canal to the
      level of CEJ. In the remaining experimental groups, glass-ionomer (GI) was used
      as a coronal barrier. After a 24-hour incubation period, one of the following
      three bleaching agents was placed in the access cavity of each of the WMTA or GI
      groups. These three bleaching agents were 30% hydrogen peroxide, sodium perborate
      mixed with 30% hydrogen peroxide, and sodium perborate mixed with distilled
      water. The bleaching agents were replaced every 3 days for three times. In the
      positive controls, no coronal barrier was used. In the negative controls, all the
      tooth surfaces were covered by two layers of nail varnish. Microleakage was
      evaluated using protein leakage test. Statistical analyses were performed with
      the Kruskal-Wallis and Mann-Whitney tests. RESULTS: The experimental groups
      showed minimum leakage which was not significantly more than tha in the negative
      controls. There was no statistically significant difference in leakage between
      the experimental groups (p<0.05). CONCLUSIONS: This study indicated that
      different bleaching agents have no effect on sealing ability of WMTA.

PMID- 21743400
TI  - Early diagnosis of osteoporosis by means of orthopantomograms and oral x-rays: a
      systematic review.
AB  - Osteoporosis is a systemic bone disease that is characterized by a generalized
      reduction of the bone mass. It is the main cause of fractures in elderly women.
      Bone densitometry is used in the lumbar spine and hip in order to detect
      osteoporosis in its early stages. Different studies have observed a correlation
      between the bone mineral density of the jaw (BMD) and that of the lumbar spine
      and/or hip. On the other hand, there are studies that evaluate the findings in
      the orthopantomograms and perapical X-rays, correlating them with the early
      diagnosis of osteoporosis and highlighting the role of the dentist in the early
      diagnosis of this disease. MATERIALS AND METHODS: A search was carried out in the
      Medline-Pubmed database in order to identify those articles that deal with the
      association between the X-ray findings observed in the orthopantomograms and the
      diagnosis of the osteoporosis, as well as those that deal with the bone mineral
      density of the jaw. RESULTS: There were 406 articles, and with the limits
      established, this number was reduced to 21. Almost all of the articles indicate
      that when examining oral X-rays, it is possible to detect signs indicative of
      osteoporosis. DISCUSSION: The radiomorphometric indices use measurements in
      orthopantomograms and evaluate possible loss of bone mineral density.  They can
      be analyzed alone or along with the visual indices. In the periapical X-rays, the
      photodensimetric analyses and the trabecular pattern appear to be the most
      useful. There are seven studies that analyze the densitometry of the jaw, but
      only three do so independently of the photodensitometric analysis. CONCLUSIONS:
      The combination of mandibular indices, along with surveys on the risk of
      fracture, can be useful as indicators of early diagnosis of osteoporosis. Visual
      and morphometric indices appear to be especially important in the
      orthopantomograms. Photodensitometry indices and the trabecular pattern are used
      in periapical X-rays. Studies on mandibular dual-energy X-ray absorptiometry are
      inconclusive.

PMID- 21743401
TI  - A preliminary study of hardness and modulus of elasticity in sheep mandibles
      submitted to distraction osteogenesis and low-level laser therapy.
AB  - OBJECTIVES: To investigate the quality of newly formed bone in sheep mandibles
      submitted to distraction osteogenesis and low-level laser therapy (LLLT), based
      on hardness and modulus of elasticity values. The ideal moment for laser
      application (during the latency/activation period vs. during the bone
      consolidation period) was also evaluated. Computed tomography imaging was used to
      assess relapse as a result of early device removal. STUDY DESIGN: Extraoral
      distraction devices were placed in five sheep so as to achieve 1.5 cm of
      lengthened bone in 60 days. Distraction devices were removed 50, 40, and 33 days
      after surgery. Four animals were treated with LLLT, at different times, and one
      was used as control (no LLLT). RESULTS: When applied during the bone
      consolidation period, LLLT caused an increase in hardness and modulus of
      elasticity values. On the other hand, animals irradiated with LLLT during the
      latency/activation period presented a delay in bone healing. A period of
      consolidation of 13 days (early device removal) was associated with relapse.
      CONCLUSIONS: Nanoindentation tests were able to detect slight abnormalities in
      bone metabolism and proved to be important tools for the assessment of bone
      quality following distraction osteogenesis. LLLT provided increased benefits when
      applied during the bone consolidation period, once it promoted an increase in
      hardness and modulus of elasticity values. According to our results, the bone
      consolidation period should be of at least 3 weeks, so as to prevent relapse.

PMID- 21743402
TI  - Applications of OralCDx(r) methodology in the diagnosis of oral leukoplakia.
AB  - OBJECTIVE: We aim to evaluate the effectiveness of the brush biopsy technique
      using OralCDx (r) (OralScan Laboratories Inc., Suffern, NY) as a new method for
      early diagnosis and control of a "potentially malignant disorder" such as oral
      leukoplakia. DESIGN OF THE STUDY: We performed a study in which samples were
      taken using OralCDx (r) on 24 patients who visited the Master of Oral Medicine,
      Oral Surgery and Implantology of the University of Santiago de Compostela between
      February 2009 and May 2010. These patients presented clinical and histological
      lesions that were consistent with oral leukoplakia. We evaluated the relationship
      between the keratinization degree of the lesions and cell representation; the
      diagnosis obtained through OralCDx (r) and biopsies; and sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV).
      RESULTS: 50% of patients were men and 50% women with an average age of 62.38
      years. The Kappa coefficient relating keratinization of lesions and cell
      representation was 0.33, the OralCDx (r) - biopsy diagnostic rate reached a Kappa
      value of 0.66, recording 72.7%, sensitivity and 92.3% specificity, PPV was 88.8%,
      while NPV reached 80%. CONCLUSIONS: cytology sampling with OralCDx (r) showed
      high sensitivity and specificity values, which make it a good tool for monitoring
      oral leukoplakia, but nowadays the most reliable method that allows us to confirm
      the exact diagnosis of the lesions and their anatomical and pathological
      characteristics still is conventional biopsy using a surgical scalpel.

PMID- 21743403
TI  - The occupational role of dental conditions among a  consecutive sample of Spanish
      workers.
AB  - OBJECTIVES: To assess the occupational impact of the mouth in terms of days of
      work loss in the last year and the perception of the working performance
      disturbance because of the oral conditions. STUDY DESIGN: A consecutive sample
      (n=269) of the Regional Government staff of the province of Granada (Spain) was
      recruited. Participants were asked about work loss related to health problems in
      the past 12 months, capturing the aetiological entities, the frequency of the
      work absent and the total days loss. Also subjects reported if they believed that
      mouth affects their occupational performance, and if they have perceived
      difficulties for carrying out work because of the mouth. Data on
      sociodemographic, behavioural and clinical factors were also gathered. Chi
      squared test, Odds ratio (OR) and relative risk (RR) of perceived occupational
      role were used to quantify the effect of the modulating factors. RESULTS: Almost
      40% of individuals were absent from work during the last year spending on average
      5.4 days for recovering. Colds and musculoskeletal pathology were the major
      causes of sick leave. Dental disease caused short work absences (4 days on
      average) only in 2.8% of participants. However most of workers (62.5%) considered
      mouth to influence their occupational performance, mainly because of the pain
      related events (61.7%), but only 4.1% of workers reported difficulties in
      carrying out their work in the past 12 months. Females (RR=1.3), participants
      attending regular dental visits (RR=1.4) and denture wearers (RR=2.5) were shown
      to have significantly higher risk of perceiving an occupational role of the
      mouth. Those workers reporting that mouth influences their work have
      significantly poorer oral health than counterparts. CONCLUSIONS: Most workers
      considered that mouth influences their occupational performance but dental
      disease has demonstrated to be a minor occupational cause of sick leave in terms
      of prevalence and magnitude of work loss.

PMID- 21743404
TI  - Current state of dental autotransplantation.
AB  - The aim of this study is to analyse the current situation in dental
      autotransplantations within the different therapeutic alternatives that the
      Dentist has available to replace a tooth in the dental arcade.  For some authors
      this is an option headed for failure, whereas for others, it is an alternative to
      keep in mind. In this study we analyse the factors related to the predictability
      of the technique, based on an analysis of research work published in the
      scientific literature up to date. We also present two clinical cases performed by
      our team and their subsequent evaluation. In spite of the satisfactory results
      seen when reviewing the existing literature, we cannot say that dental
      autotransplantation is currently the technique of choice when a tooth is lost,
      given the predictability of osteointegrated implants.

PMID- 21743405
TI  - Prevalence of traumatic dental injuries and role of incisal overjet and
      inadequate lip coverage as risk factors among 4-15 years old government school
      children in Baddi-Barotiwala Area, Himachal Pradesh, India.
AB  - OBJECTIVE: To assess the prevalence of traumatic dental injuries (TDI) in school
      children in Baddi- Barotiwala, Himachal Pradesh, India. METHODS: A cross
      sectional survey was carried out in Government schools among 1059 government
      school children aged 4- 15 years. The study was conducted from October 2009 to
      March 2010 during the school hours. The demographic detail was carried on a
      structured questionnaire. The data regarding the traumatic injuries was recorded
      using modified Ellis' classification. RESULTS: Prevalence of TDI was found to be
      4.15 %. 95.45% of the injuries were to the maxillary anterior teeth. Maxillary
      central incisor was the most common tooth to be affected due to trauma (54.5 %).
      Enamel with dentin fracture with pulp exposure was the main type of TDI (43.1%).
      The majority of TDIs were untreated (97.7 %). Falls (54.5%) were found to be the
      main cause. Over jet over 3 mm and inadequate lip coverage were found to be
      important contributing factors for TDIs. CONCLUSION: The present study revealed a
      relatively low prevalence of dental trauma, but still this figure represents a
      large number of children. Therefore, educational programs are to be initiated for
      the community regarding causes, prevention and treatment of traumatic dental
      injuries. It is crucial to generate considerable efforts to implement health
      promotion strategies to reverse the observed trends and to provide treatment to
      TDIs to prevent their biologic and psychological consequences.

PMID- 21743406
TI  - Clinical-therapeutic management of drooling: Review and update.
AB  - Drooling is the uncontrolled leakage of saliva outside the mouth, generally as a
      result of difficulty in swallowing the saliva produced. Many factors contribute
      to drooling, though it is more commonly seen in children with brain paralysis -
      particularly those receiving anticonvulsivant medication. Drooling is also often
      seen in patients with lip sealing problems or malocclusions such as anterior open
      bite. Clinically, the affected patients can develop skin irritation or abrasions,
      problems of hygiene, unpleasant smell and - in the more severe presentations -
      the need to wear protectors or frequently change clothing. Treatment of this
      disorder is complex, and should be addressed from a multidisciplinary
      perspective, with planning on an individualized basis. Among the different
      existing managements, myofunctional therapy, behavioral change programs and drug
      treatments are the most widely used options, though there are also more invasive
      surgical techniques designed to reduce or cause submandibular saliva secretion to
      be rerouted towards posterior zones of the oral cavity. In any case, no
      scientific evidence-based management protocol has yet been established capable of
      affording favorable results in the majority of cases. The present study offers a
      review and update on the clinical and dental management aspects of drooling.

PMID- 21743407
TI  - Clinico-therapeutic management of osteoradionecrosis: a literature review and
      update.
AB  - In the management of head and neck cancer, radiotherapy is usually a coadjuvant
      to surgery, or is applied on a palliative basis. The most important complication
      of such radiotherapy is osteoradionecrosis, which manifests as an area of exposed
      necrotic bone in the maxillae or mandible that fails to heal during at least
      three months. In most cases osteoradionecrosis gradually progresses, becoming
      more extensive and painful, and its late manifestations comprise infection and
      pathological fracture. The present study provides a literature review and update
      on the risk factors underlying osteoradionecrosis, its clinical and diagnostic
      particulars, prevention, and most widely accepted treatment options, as well as
      new possibilities relating to clinical management of the disorder. Lastly, a new
      early management protocol is proposed based on the current consensus criteria
      relating to maxillary osteonecrosis secondary to treatment with bisphosphonates,
      together with the adoption of new therapies supported by increased levels of
      evidence.

PMID- 21743408
TI  - Odontogenic tumors: a study of 120 cases in an Indian teaching hospital.
AB  - OBJECTIVE: Studies on odontogenic tumors published from many parts of the world
      show a distinct geographic variation; however, there is little information
      available in the English-language literature on the relative frequency of
      odontogenic tumors in India. This retrospective study was designed to determine
      the relative frequency of odontogenic tumors in an Indian population and compare
      them with various reports from other parts of the world. STUDY DESIGN: The
      histopathology records of the Department of Oral Pathology and Microbiology of
      Government Dental College and Hospital, Mumbai were retrieved retrospectively
      within the period of January 2001 to July 2010. A total of 120 lesions classified
      as odontogenic tumors were reviewed. These were analyzed for age, gender, site of
      tumor and histopathologic typing. Criteria used were World Health Organization
      (WHO) classification 2005. The mandible and maxilla were divided into 4 anatomic
      regions, and the distribution of each odontogenic tumor among these regions was
      recorded and analyzed. RESULTS: A total of 120 cases of odontogenic tumors were
      reported in this period. Odontogenic tumors in the present study constituted
      5.78% of all the 2075 registered biopsies. The most frequent histological type
      was ameloblastoma (40.83%), followed by Keratocystic odontogenic tumor (37.5%),
      odontome (11.66%) and adenomatoid odontogenic tumor (5.8%). In general, the
      odontogenic tumors showed a predilection for the mandible and the posterior
      regions of the jaws. Ameloblastomas occurred with a marked predilection for the
      mandible, while adenomatoid odontogenic tumor showed predilection for the
      maxilla, anterior regions of the jaws, and young females. CONCLUSION: A frequency
      of 5.78% of odontogenic tumors was observed in this study. Ameloblastoma
      comprised the single most common tumor of all odontogenic tumors. This study
      observed geographic variations in the frequency and distribution of odontogenic
      tumors.

PMID- 21743409
TI  - The influence of platform switching on the biomechanical aspects of the implant
      abutment system. A three dimensional finite element study.
AB  - OBJECTIVE: To evaluate the biomechanical scenario of platform switching geometric
      implant-abutment configuration relative to standard configurations by means of
      finite element analysis. STUDY DESIGN: A 3D Finite Element Analysis (FEA) was
      performed on 3 different implant-abutment configurations: a 3.8 mm implant with a
      matching diameter abutment (Standard Control Design, SCD), a 5.5 mm implant with
      matching diameter abutment (Wider Control Design, WCD), and a 5.5mm implant with
      a 3.8 mm abutment (Experimental Design, ED). All the different experimental
      groups were discretized to over 60000 elements and 100000 nodes, and 130N
      vertical (axial) and 90N horizontal loads were applied on the coronal portion of
      the abutment. Von Mises stresses were evaluated and maximum and minimum values
      were acquired for each implant-abutment configuration. RESULTS: The load-induced
      Von Mises stress (maximum to minumum ranges) on the implant ranged from 150 MPa
      to 58 Pa (SCD); 45 MPa to 55 Pa (WCD); 190 MPa to 64 Pa (ED). The Von Mises
      stress on the abutment ranged from 150 MPa to 52 MPa (SCD); 70 MPa to 55 MPa
      (WCD), and 85 MPa to 42 MPa respectively (ED). The maximum stresses transmitted
      from the implant-abutment system to the cortical and trabecular bone were 67 Pa
      and 52 MPa (SCD); 54 Pa and 27 MPa (WCD); 64 Pa and 42 MPa (ED), respectively.
      When the implant body was evaluated for stresses, a substantial decrease in their
      levels were observed at the threaded implant region due to the diametral mismatch
      between implant and abutment for the ED configuration. CONCLUSION: The platform
      switching configuration led to not only to a relative decrease in stress levels
      compared to narrow and wide standard configurations, but also to a notable stress
      field shift from bone towards the implant system, potentially resulting in lower
      crestal bone overloading.

PMID- 21743410
TI  - Microbiological effects of an antiseptic mouthrinse  in irradiated cancer
      patients.
AB  - OBJECTIVE: To assess the microbiological effects of an antiseptic, non-alcohol
      based mouth-rinse containing chlorhexidine and cetylpyridinium chloride, in
      patients undergoing radiation therapy for head-and-neck cancer. STUDY DESIGN:
      This was a parallel, double-blind, prospective, randomized clinical trial,
      including patients irradiated as part of the therapy of head-and-neck cancer,
      aged 18-75, with at least 10 teeth, and willing to sign an informed consent.
      Cancer patients were randomly assigned to one of the two treatments (test mouth
      rinse or a placebo). Three visits were scheduled (baseline, 14 and 28 days).
      Microbiological findings were evaluated in tongue, mucosa and subgingival
      samples, by means of culture. Microbiological variables were assessed by means of
      the Mann-Whitney, Wilcoxon and chi-square tests. RESULTS: 70 patients were
      screened and 36 were included. The detection of Candida species in mucosa and
      tongue samples showed significant reductions in the test group. Total bacterial
      counts decreased in both groups from baseline to the 2-week visit, while minor
      changes occurred between 2 and 4 weeks (effects on P. gingivalis, P. intermedia,
      C. rectus, E. corrodens). CONCLUSIONS: Within the limitations of the small sample
      size, this study suggests that the use of the tested mouth-rinse may lead to
      improvements in microbiological parameters in patients irradiated for head-and
      neck cancer.

PMID- 21743411
TI  - Analysis of the peri-implant microbiota in 90 dental implants and its 
      relationship to crevicular fluid volume.
AB  - OBJECTIVE: To evaluate the presence within the peri-implant sulcus of Tannerela
      forsythia (Tf), Porphyromonas gingivales (Pg), Treponema denticola (Td) and
      Aggregatibacter actinomycetemcomitans (Aa), and relate these bacteria to the peri
      implant crevicular fluid volume (PICFV). MATERIAL AND METHOD: A prospective and
      cross-sectional clinical case series study was made. For the measurement of
      crevicular fluid, use was made of the Periotron(r) 8000 (Proflow Incorporated.
      New York, USA), measuring the volume in Periotron units (PU). For the detection
      of periodontopathogenic bacteria we used the IAI-PadoTest 4.5 (IAI Inc., IAI
      Institute, Zuchwil, Switzerland) - a system for the detection of Tf, Pg, Td and
      Aa based on the use of RNA arrays. RESULTS: We included 34 patients (19 females
      and 15 males) with a mean age of 56.4 years. Of these subjects, 30.8% were
      smokers and 69.2% non-smokers. Out of a total series of 213 implants, we analyzed
      the crevicular fluid and microbiota in 90 implants. A total of 16.5% of the
      implants presented mucositis, while 83.5% were in healthy peri-implant
      conditions. The microbiological study revealed the presence of Tf in 17.1% of the
      implants, Pg in 9.3%, Td in 13.6%, in Aa in none of the implants. The mean
      Periotron reading was 93.4 PU (range 12-198 PU). A statistically significant
      (p<0.05) relationship was observed between PICFV and the total percentage
      bacteria (Tf, Pg and Td) - with a strong association between the Td levels and
      smoking (p<0.01). In the implants with mucositis, the concentration of Pg and Td
      was greater. CONCLUSIONS: In the implants studied, the subgingival peri-implant
      microbiota was characterized by low levels of Pg, Tf, Td, and none of the
      patients proved positive for Aa. These bacteria showed a positive correlation to
      crevicular fluid volume, and a statistically significant relationship was
      observed between Td and smoking.

PMID- 21743412
TI  - Peri-implantitis: associated microbiota and treatment.
AB  - INTRODUCTION: Peri-implantitis is a late complication of dental implant
      treatment, induced by microbiological changes. Since the disorder is frequent, a
      review is indicated of the microorganisms that influence it and of the existing
      treatment options. OBJECTIVE: To conduct a literature review of the microbiota
      associated to peri-implantitis and the existing treatment options. MATERIAL AND
      METHOD: A PubMed literature search was made of the studies on the microbiota
      associated to dental implants in healthy patients and patients with peri
      implantitis, as well as of the latest treatment developments, using the following
      key words: "peri-implantitis AND microbiota", "periimplantitis AND microbiota",
      "peri-implantitis AND treatment", and "periimplantitis AND treatment". Only
      clinical studies in humans were considered. The following criteria were applied
      for including articles in the analysis: a) for the peri-implant microbiota, the
      search limits were human studies after the year 2000; and b) for the treatment of
      peri-implantitis, the search limits were randomized and controlled clinical
      trials (RCTs) in humans, with a minimum follow-up of 4 months, and publication
      after the year 2000. RESULTS: A total of 18 articles were selected in relation to
      peri-implant microbiota, and 13 in relation to the treatment of peri-implantitis
      (8 involving nonsurgical mechanical treatments and 5 surgical procedures).
      CONCLUSIONS: Evaluation of the literature has shown the microbiota associated to
      peri-implantitis to be more complex than that found under healthy peri-implant
      conditions - the main flora consisting of anaerobic gramnegative bacteria. No
      clear criteria have been identified for the diagnosis and treatment of peri
      implantitis.

PMID- 21743413
TI  - Burning mouth syndrome: correlation of treatment to clinical variables of the
      disease.
AB  - OBJECTIVE: Burning mouth syndrome (BMS) is a complex disorder with a still
      uncertain etiopathogenesis. A number of treatments have been used in application
      to BMS, though without clearly successful results. The present study compares the
      improvement in BMS obtained as a result of different treatment modalities in
      relation to the clinical characteristics of the patients. STUDY DESIGN: A
      retrospective cohort study was made of 115 patients with BMS (109 females and 6
      males) subjected to different treatments with a view to improving the symptoms.
      The clinical variables examined included the duration of the disorder, the
      location of the burning sensation, its daily variations and relationship with
      meals. The parameters were measured using a visual analog scale (VAS) applied at
      baseline and again after two weeks of treatment. RESULTS: The mean patient age
      was 70 +/- 11.41 years, and the mean duration of the syndrome was 7.16 +/- 2.63
      years. The tongue was the most frequently affected location. Anxiolytic treatment
      afforded the best results (p < 0.001), and the patients with the shortest
      duration of disease showed the best improvement with treatment (p = 0.005).
      CONCLUSION: The greatest treatment efficacy corresponded to anxiolytic drugs, and
      treatment was more effective when introduced early after the diagnosis of BMS.

PMID- 21743414
TI  - Relationship between oral cancer and implants:  clinical cases and systematic
      literature review.
AB  - The use of implants for oral rehabilitation of edentulous spaces has recently
      been on the increase, which has also led to an increase in complications such as
      peri-implant inflammation or peri-implantitis. Chronic inflammation is a risk
      factor for developing oral squamous cell carcinoma (OSCC). OBJECTIVES: To review
      the literature of cases that associate implant placement with the development of
      oral cancer. STUDY DESIGN: We present two clinical cases and a systematic review
      of literature published on the relationship between oral cancer and implants.
      RESULTS: We found 13 articles published between the years 1996 and 2009,
      referencing 18 cases in which the osseointegrated implants are associated with
      oral squamous cell carcinoma. Of those, 6 articles were excluded because they did
      not meet the inclusion criteria. Of the 18 cases reported, only 7 cases did not
      present a previous history of oral cancer or cancer in other parts of the body.
      CONCLUSIONS: Based on the review of these cases, a clear cause-effect
      relationship cannot be established, although it can be deduced that there is a
      possibility that implant treatment may constitute an irritant and/or inflammatory
      cofactor which contributes to the formation and/or development of OSCC.

PMID- 21743415
TI  - Application of a capsaicin rinse in the treatment of burning mouth syndrome.
AB  - OBJECTIVE: To examine the efficacy of a new topical capsaicin presentation as an
      oral rinse in improving the symptoms of burning mouth syndrome (BMS). STUDY
      DESIGN: A prospective, double-blind, cross-over study was made of 30 patients
      with BMS. There were 7 dropouts; the final study series thus comprised 23
      individuals. The patients were randomized to two groups: (A) capsaicin rinse
      (0.02%) or (B) placebo rinse, administered during one week. After a one-week
      washout period, the patients were then assigned to the opposite group. Burning
      discomfort was scored using a visual analog scale (VAS): in the morning before
      starting the treatment, in the afternoon on the first day of treatment, and at
      the end of the week of treatment in the morning and in the afternoon. The same
      scoring sequence was again applied one week later with the opposite rinse.
      RESULTS: The mean patient age was 72.65 +/- 12.10 years, and the duration of BMS
      was 5.43 +/- 3.23 years on average. Significant differences in VAS score were
      recorded in the capsaicin group between baseline in the morning (AM1) or
      afternoon (AA1) and the end of the week of treatment (AA7)(p=0.003 and p=0.002,
      respectively). CONCLUSION: The topical application of capsaicin may be useful in
      treating the discomfort of BMS, but has some limitations.

PMID- 21743416
TI  - Epidemiology and treatment of adenoid cystic carcinoma of the minor salivary
      glands: a meta-analytic study.
AB  - OBJECTIVES: To evaluate the epidemiological aspects of adenoid cystic carcinoma
      (ACC) and to evaluate the different therapeutic possibilities as well as the
      percentage of survival. STUDY DESIGN: A retrospective, meta-analytic,
      observational study was carried out by selecting a total of 13 articles, which
      provided a sample size of 263 cases of patients who had been diagnosed with ACC
      in the minor salivary glands. RESULTS: ACC was found to be more common among
      women (56.5%) and the average age at diagnosis was 55.26 years old. The primary
      location of the tumor was in the palate in 57% of the cases, the predominant
      pattern being cribiform. The treatment of choice was therapy combined with
      surgery and radiotherapy in 62.7% of the subjects. The overall survival rate was
      70.76% and 56.76%, at 5 and 10 years respectively. CONCLUSIONS: Early detection
      of adenoid cystic carcinoma is necessary in order to enable making an earlier
      prognosis and thus enable a better quality of life for the patient.

PMID- 21743417
TI  - In vitro evaluation of the efficacy of two bleaching procedures.
AB  - OBJECTIVE: In vitro comparison of the efficacy of two bleaching procedures, one
      based on carbamide peroxide (CP) and the other on hydrogen peroxide (HP),
      simulating clinical conditions. STUDY DESIGN: Two groups of 20 teeth in each
      group were selected. Group A: 22% CP, one hour a day for 21 consecutive days.
      Group B: 37.5% HP, in 2 treatment sessions with an one week interval between each
      session. At each session the product was applied three successive times for eight
      minutes. Colour was recorded before treatment, when it was finished and one week
      after finishing it, with the Vita EasyShade spectrophotometer. CIEL*a*b* and
      DeltaE were established at each moment in the study. Intra-group data was
      compared using the paired t-test and inter-group data with the independent groups
      t-test. Scores from the Vita Classical guide provided with the device were
      recorded and the colour improvement percentage was calculated. RESULTS: In both
      groups significant whitening was achieved by the end of treatment. Lightness
      remained significantly high when treatment was finished and one week after in
      both groups. The percentage of bleaching was significantly higher in group A.
      CONCLUSIONS: Both 22% CP and 37.5% HP were effective for bleaching teeth.
      Bleaching effect was greater in CP group.

PMID- 21743418
TI  - Management of immature teeth by dentin-pulp regeneration: a recent approach.
AB  - Treatment of the young permanent tooth with a necrotic root canal system and an
      incompletely developed root is very difficult and challenging. Few acceptable
      results have been achieved through apexification but use of long-term calcium
      hydroxide might alter the mechanical properties of dentin. Thus, one alternative
      approach is to develop and restore a functional pulp-dentin complex. Procedures
      attempting to preserve the potentially remaining dental pulp stem cells and
      mesenchymal stem cells of the apical papilla can result in canal
      revascularization and the completion of root maturation. There are several
      advantages of promoting apexogenesis in immature teeth with open apices. It
      encourages a longer and thicker root to develop thus decreasing the propensity of
      long term root fracture. So, the present article reviews the recent approach of
      regeneration of pulp-dentin complex in immature permanent teeth.

PMID- 21743419
TI  - Antibacterial susceptibility patterns of Porphyromonas gingivalis isolated from
      chronic periodontitis patients.
AB  - OBJECTIVES: To test the antimicrobial sensitivity of Porphyromonas gingivalis to
      a panel of eight orally administrable antibiotics in chronic periodontal diseases
      and to evaluate factors associated with periodontitis in adult patients. STUDY
      DESIGN: A total of fifty strains of P. gingivalis were isolated from one hundred
      and twenty adult patients with chronic perio-dontitis. Identification of bacteria
      was carried out by anaerobic culture and biochemical tests. Selected colonies of
      P. gingivalis were used to evaluate the antibacterial activities of penicillin,
      metronidazole, amoxicillin, amoxicillin/clavulanic acid, clindamycin, doxy
      cycline, ciprofloxacin and azithromycin. RESULTS: Most of the patients were
      female, age ranging between 40 to 50 years. Majority of the patients frequently
      had scaling and depths of periodontal pockets in infected teeth were 5-8 mm and
      most of them had hemorrhage during sampling. Susceptibility testing revealed a
      sensitivity of 100% of P. gingivalis to azithromycin, doxycycline and
      amoxicillin/clavulanic acid but lower susceptibilities were found for the rest of
      antibiotic agents evaluated. CONCLUSIONS: Frequent scaling in women aged between
      40-50 years had positive correlation with chronic periodontitis. The application
      of antibiotics in conjuction with mechanical debridation, may reflect in the
      level of resistance of P. gingivalis in patients with chronic periodontal
      infections. This could suggest periodical antibiotic susceptibility testing is
      necessary to determine the efficacy of antimicrobial agents if the perfect curing
      of chronic periodontal diseases after mechanical debridation is meant. Further
      clinical studies are required to confirm the in vitro results. The only
      limitation in this study was identification of bacteria to species rather than
      subspecies level.

PMID- 21743420
TI  - No association between periodontal disease and GHQ-12 in a Brazilian Police
      population.
AB  - OBJECTIVES: We attempt to investigate a possible association between periodontal
      disease (PD) and mental disorders (MD) in a population of Brazilian Police. STUDY
      METHOD: From a total study population consisting of 803 policemen, 345 police
      officers were obtained by a sample calculation using the finite population
      correction who were randomly selected in Montes Claros, Minas Gerais, Brazil.
      Patients who had been prescribed steroids or those diagnosed with diabetes and
      cardiovascular diseases were excluded from this study. The General Health
      Questionnaire (GHQ-12) was used to assess mental disorders. Odds ratios (ORs) for
      periodontal diseases severity and their respective 95% confidence intervals (CIs)
      were estimated. The risk of advanced scores in Clinical Attachment Level (CAL)
      and Community Periodontal Index (CPI) were estimated using Poisson Regression
      analyses. RESULTS: Only smoking and age were associated with severity in CAL and
      CPI index. No relation between MD and PD was observed even in different positions
      within the police department. CONCLUSIONS: It was not observed relation between
      GHQ-12 and the incidence of Periodontal Disease in a Brazilian Police population.
      Classical factors like age and smoking, however, were associated with CAL and CPI
      index higher scores in this population.

PMID- 21743421
TI  - Effect of alkaline ph on sealing ability of white mineral trioxide aggregate.
AB  - OBJECTIVES: The aim of this study was to evaluate microleakage of white mineral
      trioxide aggregate (WMTA) after its exposure to a range of alkaline environments
      during hydration. STUDY DESIGN: Seventy single-rooted teeth were divided into 4
      experimental and 2 control groups. All the teeth were instrumented, and their
      apices were resected. Root-end cavities were filled with WMTA in the experimental
      groups. In the control groups, root-end cavities were not filled. Root-end
      fillings were exposed to alkaline environments with pH values of 7.4, 8.4, 9.4,
      or 10.4 for 3 days. Microleakage was evaluated by bovine serum albumin.
      Evaluations were carried out at 24-hour intervals for 80 days. Data were analyzed
      by one-way analysis of variance and a post hoc Tukey test at the 0.05 level of
      confidence. RESULTS: The number of days (mean +/- standard deviation) needed for
      color change at pH values of 7.4, 8.4, 9.4, and 10.4 were 78.53 +/- 5.68, 80.00
      +/- 0.00, 68.93 +/- 19.00, and 34.46 +/- 12.73, respectively. The time needed for
      leakage to occur was significantly shorter in samples stored at a pH value of
      10.4 (P<0.001). CONCLUSIONS: Within the limits of this study, it can be concluded
      that pH values greater than 9.4 may jeopardize the sealing ability of WMTA during
      hydration.

PMID- 21743422
TI  - Extraction socket healing in rats treated with bisphosphonate: animal model for
      bisphosphonate related osteonecrosis of jaws in multiple myeloma patients.
AB  - AIM: The aim of this study is to replicate both clinical and histological
      presentation of bisphosphonate induced osteonecrosis of the jaws (BONJ) in an
      animal model of the disease state. Successful recapitulation of a BONJ-like
      indication in an animal model will be useful for studying pathogenesis, as well
      as prevention and treatment strategies for BONJ. MATERIALS AND METHODS: Eighty
      (80) rats were prospectively and randomly divided into two groups; control
      group(40) and study group(40). All animals in study group, injected with a dose
      of 1 mg/kg dexamethasone (DX) subcutaneously on day 7, 14, or 21; and 1, 2, or 3
      doses of 7.5 ug/kg zoledronic acid (ZA) subcutaneously administered to coincide
      with the last day of DX. Half of the animals from each group underwent extraction
      of the left mandibular molars and the remaining animals underwent extraction of
      the left maxillary molars under pentobarbital-induced general anesthesia. All
      animals were euthanized twenty-eight (28) days following tooth extractions.
      RESULTS: The amount of new bone trabecules as significantly decreased in
      bisphosphonate-dexamethasone (BP-DX) treated sockets. Difference between both
      groups was found statistically significant (p=0,0001). There's no foreign body
      reaction in sockets of both groups and no significance difference observed for
      fibrosis (p=0,306). The necrosis scores were significantly higher in BP-DX
      treated sockets (p=0,015). The inflamation scores were significantly higher for
      study group (p=0,0001). CONCLUSION: This study provides preliminary observations
      for the development of an animal model of BONJ. But we think that there is need
      for other studies have only BP treated group and larger study population.

PMID- 21743423
TI  - An analysis of oral biopsies extracted from 1995 to 2009, in an oral medicine and
      surgery unit in Galicia (Spain).
AB  - OBJECTIVE: To conduct an analysis of the frequency of oral lesions in biopsies
      over a 14-year period in the Oral Medicine, Oral Surgery and Implantology Unit.
      MATERIAL AND METHODS: We conducted a retrospective study of biopsies removed from
      1995-2009, recording data regarding age, sex, location of the lesions, biopsy
      types, anatomical and pathological diagnosis and definitive diagnosis. RESULTS:
      Of the 562 patients studied, the average age was 51.8 years, with a standard
      deviation of 18.5 (range 5-96). The distribution by sex was 318 (56.6%) women and
      244 (43.4%) men. The most common diagnostic category was mucosal pathologies in
      37.9% of cases, followed by odontogenic cysts in 27.8%. Malignant tumors
      accounted for 3.9% of cases, oral squamous cell carcinomas were the most frequent
      malignancy, appearing in 22 cases. Bisphosphonate-related osteonecrosis of the
      jaws was the most common injury within the bone lesions group. CONCLUSION:
      Following the performance of 647 biopsies on 562 patients, we can say that the
      most common injury was radicular cysts (appearing in 108 cases), having found
      statistical differences in relation to the patients' sex and age.

PMID- 21743424
TI  - Effect of postbleaching application of an antioxidant on enamel bond strength of
      three different adhesives.
AB  - OBJECTIVES: The aim of this study was to compare the shear bond strength (sbs) of
      three different adhesives on bleached enamel immediately after bleaching,
      bleached/delayed for 1 week, and bleached/applied antioxidizing agent. STUDY
      DESIGN: The enamel surfaces of 144 freshly extracted incisors without any caries
      and restorations were flattened and divided into 12 groups. The following
      adhesives were investigated: Optibond FL (OFL) (three-step etch&rinse), Optibond
      Solo Plus (OSP) (two-step etch&rinse), Optibond All-in-One (OA) (one-step self
      etch), (Kerr, Orange, USA). Unbleached enamel groups were prepared as negative
      controls. The remainder surfaces were bleached with 20% Opalescent PF (Ultradent,
      USA) 6 h/d for 5 consecutive days. Specimens were bonded immediately after
      bleaching, after 1 week or after using 10% sodium ascorbate gel for 6 hours.
      After 500 rounds of thermocycling, sbs was measured and data was analyzed with
      Kruskall-Wallis and Mann-Whitney U-tests ( = 0.05). RESULTS: The sbs decreased
      for the adhesives after bleaching except for OFL. The effect of applying sodium
      ascorbate subsequent to bleaching was not equal for the studied adhesives. While
      for OFL, sbs of the sodium ascorbate group was significantly higher than the
      unbleached control group, for OSP, the sodium ascorbate group had no
      statistically significant difference with the unbleached control group and for
      OA, sbs was significantly lower than the unbleached control group. CONCLUSIONS:
      Different adhesives demonstrate different degrees of reversed bond strength
      subsequent to applying antioxidant. It seems the method of application and the
      chemical composition of the adhesives could affect the antioxidant as a reducing
      agent.

PMID- 21743425
TI  - Irritative and sensory disturbances in oral implantology. Literature review.
AB  - The aim of this study was to review irritative and sensory disturbances following
      placement of dental implants. A literature search was made of PubMed for articles
      published between 2000 and 2010. Studies that reported sensory disturbances
      directly caused by the placement of dental implants were included.  Sensory
      deficits or trigeminal neuropathy are caused by damage to the third branch of the
      trigeminal nerve during surgery. This manifests in the immediate postoperative
      period as a sensory deficit not usually associated with pain and generally
      transient. The literature reviewed reported irritative and sensory disturbances
      caused during surgery, after surgery, and as a result of complications.
      Postoperative pain appears after oral surgery as a result of inflammation
      associated with damage to tissue during surgery. Pain due to postoperative
      complications following implant placement was classified as neurogenic pain, peri
      implant pain and bone pain.

PMID- 21743426
TI  - Oral Health: Validation of a questionnaire of self-perception and self-care
      habits in Diabetes Mellitus 2, hypertensive and obese patients. The UISESS-B
      scale.
AB  - OBJECTIVES: To develop and to evaluate a questionnaire of self-perception and
      self-care habits on oral health on a first level population. METHODS: A
      descriptive, observational study was performed to validate a questionnaire on
      oral health self-perception (UISESS-B). After non-probabilistic sampling, 94
      users, 30-59 years of age, with either diabetes mellitus 2, hypertension or
      obesity were included. Duration of disease was lesser than 10 years. Pearson's r,
      Cornbach's , factorial analysis, chi-square and Snedecor's F tests were employed.
      RESULTS: A Pearson's r of 0.7 and Cronbach's of 0.82 was observed on the pre-post
      values of the global questionnaire. In the factorial analysis, the variance
      explained more than 60% for a first factor. A punctuation of very high risk for
      the three groups with the scale UISESSS-B that coincides with the index CPO-D and
      the index UISESS-F was observed. CONCLUSIONS: The UISESS-B scale shows
      significant validity and reliability, suggesting its use as a sensitive
      instrument for the measurement of oral health in people with chronic illnesses
      such as diabetes, hypertension and obesity.

PMID- 21743427
TI  - Prevalence of complications after the oral rehabilitation with implant-supported
      hybrid prostheses.
AB  - OBJECTIVES: Assess the main problems referred by the patients and observed by the
      professionals after the bucodental rehabilitation with an implant-supported
      hybrid prothesis. PATIENTS AND METHODS: A retrospective study was carried out in
      which there were 43 patients included who were visited in the Department of Oral
      Surgery and Orofacial Implantology of University of Barcelona Dental School for
      one year. An oral rehabilitation with an implant-supported hybrid prosthesis was
      made to those patients. The following variables were registered: age, gender,
      number of inserted implants, type of implant and principal problems produced by
      the hybrid prosthesis. RESULTS: The rehabilitation with an implant supported
      hybrid prosthesis was only performed in 43 of 116 cases treated in one year
      (January, 2006 to January, 2007). They were 26 men and 17 women of ages between
      37 and 74 years, being the rate age of 56,5 years. The main complication recorded
      was the mucositis, associated frequently with a difficulty to carry a correct
      oral hygiene and to an overextention of the tail of resin of the prosthesis.
      Other observed problems were the peri-implantitis, the break of the acrylic teeth
      and the loss of some of the prosthetic screws. CONCLUSIONS: The most frequent
      complication after the laying of an implant supported hybrid prosthesis was the
      mucositis, associated mainly with a prosthetic tail too long and to the
      consequent difficulty of carrying a correct oral hygiene. In spite of the high
      prevalence of observed complications, most of them were mild and resolved on
      subsequent visits.

PMID- 21743428
TI  - Prevalence and distribution of odontogenic and nonodontogenic cysts in a Turkish
      population.
AB  - OBJECTIVE: To determine the relative frequency and distribution of odontogenic
      and nonodontogenic cysts in a large Turkish population. STUDY DESIGN: A
      retrospective survey of jaw cysts was undertaken at the Oral Diagnosis and
      Radiology and Oral and Maxillofacial Surgery Department, Ondokuz Mayis University
      Dental School, Samsun, Turkey. Data were retrieved from clinical files, imaging,
      and histopathology reports from 2000 to 2008; a total of 12,350 patients were
      included. In each case, we analyzed age, gender, type and number of cysts, and
      cyst location. Imaging patterns and pathologies associated with cystic lesions
      were also determined. RESULTS: The prevalence of odontogenic and nonodontogenic
      cysts was 3.51%; males were affected more frequently than females. There were 452
      odontogenic cysts (98.5%) and seven nonodontogenic cysts (1.5%). The most
      frequent odontogenic cyst was radicular (54.7%), followed by dentigerous (26.6%),
      residual (13.7%), odontogenic keratocyst (3.3%), and lateral periodontal cyst
      (0.2%). Nasopalatine duct cyst (1.5%) was the only nonodontogenic cyst. By age,
      cysts peaked in the third decade (24.2%). Concerning location, no statistically
      significant difference was found between the maxilla and mandible (p>0.05). The
      most frequent radiological feature of these lesions was unilocular cyst (93.7%).
      Pathologies associated with cystic lesions occurred in 14.7%. CONCLUSION: The
      prevalence of both odontogenic and nonodontogenic cysts were lower than that
      reported in many other studies. In our study population, cysts were mainly
      inflammatory in origin.

PMID- 21743429
TI  - Evaluation of satisfaction among relatives of mentally disabled patients who were
      users of a dental care protocol under general anaesthesia.
AB  - OBJECTIVES: In the field of action of disease associated with dependence the
      Third Health Plan of Castilla y Leon aims specifically at promoting the
      adjustment of health assistance to the needs of disabled people, according to
      their situation. Our objectives were: General: To know the satisfaction level
      among relatives or caregivers of people who were treated according to a protocol
      of dental care for mentally disabled people. Specific: To know if satisfaction is
      related to any sociodemographic characteristics of patients or to their
      pathology. STUDY DESIGN: Cross-sectional study by telephone survey, set in the
      Primary Health Area of Salamanca. The target population includes relatives or
      caregivers of mentally disabled patients who were sent to the hospital for
      treatment under general anaesthesia after being attended in Primary Dental Care
      Units, from 1st of June/2005 to 31st of May/2006. Social and demographic
      variables and patients' diseases, as well as level of satisfaction with the
      service, were studied through a survey. RESULTS: 67.4% of patients' relatives or
      caregivers answered the survey, among whom 94.7% (C.I. 95%: 89-100%) were quite
      or very satisfied with the service in general. CONCLUSION: The protocol has high
      acceptance despite its difficulties and it has achieved considerable improvements
      in several aspects of patients' life. This level of satisfaction was not related
      to any sociodemographic or clinical patient characteristics. Nevertheless,
      accessibility aspects and communication with patients may still be improved.

PMID- 21743430
TI  - Effect of self-etching primer/adhesive and conventional bonding on the shear bond
      strength in metallic and ceramic brackets.
AB  - INTRODUCTION: Bracket debonding from the tooth surface is a common problem in
      fixed orthodontics. The aims of the present study were to assess the bond
      strength and failure sites in two ways of bonding technique, with metallic and
      ceramic brackets. MATERIALS AND METHODS: One hundred premolars were assigned to 4
      groups of 25 each: Group A, metallic brackets/conventional procedure; Group B,
      metallic brackets/Transbond XT; Group C, ceramic brackets/conventional procedure;
      and Group D, ceramic brackets/Transbond XT. Transbond XT composite paste was used
      for bracket bonding and cured by conventional light-cure device. Specimens were
      subjected to thermocycling. One week after bonding shearing force was applied to
      the bracket-tooth interface. Bonding failure site optically examined using a
      stereomicroscope under 10 * magnifications and scoring was done using the
      adhesive remnant index (ARI). Data were subjected to analysis of One-way
      variance, Tukey post hoc, Chi-square and Spearman's tests. RESULTS: Mean bond
      strength (in MPa) were: group A=9.2, group B=8.5, group C=6.2 and group D=5.7.
      Bond strength differences between groups A and B, and between C and D were not
      significant, (p<0.0005). Insignificant difference found in ARI in all groups.
      CONCLUSION: The bond strengths of metallic brackets were significantly higher
      than ceramic ones and the self-etching primer produce fewer bonds than the
      conventional method (clinically acceptable).A positive correlation found between
      changes in shearing bond strength and ARI.

PMID- 21743431
TI  - Autogenous tooth transplantation: evaluation of pulp tissue regeneration.
AB  - OBJECTIVE: The aim of this study was to assess the pulp survival that occur in
      transplants of autologous teeth, by comparing two surgical techniques: the
      conventional technique (autotransplantation for newly formed alveoli), and an
      alternative technique, (autotransplants for alveoli in the initial phase of
      healing). In each surgical techniques were applied, randomly, either saline
      solution or Emdogain(r). STUDY DESIGN: The study group comprised 26 patents, in
      which 28 teeth were transplanted to recipient sockets prepared mechanically. Of
      the 28 teeth transplanted, 4 were intentional replants, and of the remainer, 11
      had the apex closed and 13 open. The mean age at the time of transplantation was
      22.34 +/- 8.14 years (mean +/- SD). The transplantation were performed by the
      same operator, with the informed consent of the patient and authorized by the
      ethical committee of the hospital. Clinical and radiological examinations were
      performed during 24 to 65 months (48 +/- 12.96; MED +/- SD), from 10 days, 1
      month, 3 months, 6 months and annually to 5.6 years. RESULTS: Only two
      transplanted teeth were lost, due persistent apical periodontitis, and one
      transplanted patient with open apex missed the treatment. In the teeth with pulp,
      we needed to perform root canal therapy in 9. In the 73% of the teeth with closed
      apex, we needed to perform root canal treatment, with no statistically
      significant difference found among closed apex and root canal therapy (p=0.083).
      In only 8% of the teeth with open apex did we need to perform root canal
      treatment, with an association between open apex and root canal therapy
      (p=0.0002). The overall success rate was 98% with significant difference for
      losses (p=0.0001). CONCLUSIONS: Although not a frequent procedure, it was
      concluded that autotransplanted teeth, performed with appropriate surgical care
      had a good prognosis, and can render a very useful service to the patients.

PMID- 21743432
TI  - The use of clinical guidelines for referral of patients with lesions suspicious
      for oral cancer may ease early diagnosis and improve education of healthcare
      professionals.
AB  - Early diagnosis and referral of oral cancer is essential. Successful
      implementation of clinical guidelines must include current practitioners and
      students. OBJECTIVE: To evaluate the diagnostic accuracy of students at oral
      cancer screening and to assess the effectiveness of clinical referral guidelines.
      STUDY DESIGN: Fifth year dental students were randomly allocated to either
      control (n=19) or experimental groups (n = 18). Both received the customary
      training in oral diagnosis. The experimental group underwent a 2 hour workshop
      where the guidelines for the referral of suspicious lesions were discussed. Three
      months later, a set of 51 clinical cases including benign, malignant, and
      precancerous conditions/lesions were used to assess the screening ability of each
      subject. RESULTS: All 37 students entered the study. Sensitivity (control group)
      ranged from 16.7% to 66.7%; the experimental group scored from 16.7% to 83.3%.
      Fifty percent of the experimental students reached sensitivity values >= 62.5% (p
      = 0.01). Diagnostic specificity (control group) spanned from 80% to 93.3% (median
      = 50%); amongst experimental group it ranged from 82.2% to 97.8% (median =
      92.8%); (p = 0.003). Concordance -control group- was X = 82.5 (SD = 3.2), and X =
      88.2 (SD = 4.3) for the experimental, (p > 0.001). Cohen's kappa test was poor (K
      < 0.40) for the controls and moderate for the experimental group. The
      experimental group referred more oral cancers urgently (p = 0.002) and left less
      unreferred cancers (0.04). This group also referred more precancerous
      lesions/conditions urgently (p = 0.02). CONCLUSIONS: The implementation of a
      clinical referral guideline at undergraduate level has proved valuable, under
      experimental conditions, to significantly increase diagnostic abilities of the
      examiners and thus to improve screening for oral cancer.

PMID- 21743433
TI  - KRAS mutant allele-specific imbalance in lung adenocarcinoma.
AB  - The significance of KRAS mutant allele-specific imbalance (MASI) in lung
      adenocarcinomas is unknown. KRAS MASI was defined as predominance of the mutant
      allele over the wild-type allele. We assessed the frequency of KRAS MASI by
      comparing peak heights of mutant and wild-type alleles on sequencing
      electropherograms and by KRAS fluorescence in situ hybridization (FISH). A review
      of sequencing electropherograms of 207 KRAS-mutated lung adenocarcinomas
      demonstrated 23 (11%) cases with the mutant allele peak higher than the wild-type
      allele peak and 15 (7%) cases with the mutant allele peak equal to the wild-type
      allele peak. Of 17 cases with the mutant allele peak higher or equal to the wild
      type allele peak, 8 (47%) showed KRAS amplification by FISH. KRAS FISH analysis
      of 36 KRAS-mutated lung adenocarcinomas with the mutant allele peak lower than
      the wild-type allele peak, 21 KRAS and EGFR wild-type and 16 EGFR-mutated
      adenocarcinomas showed no KRAS amplification. KRAS MASI was associated with
      selective amplification of the KRAS mutant allele (P<0.001). Patients with KRAS
      MASI showed worse overall survival. The cumulative proportion surviving at 17
      months for KRAS MASI group was 35% compared with 84.1% for patients with KRAS
      mutant allele peak lower than wild-type allele peak (P=0.012). The adverse
      prognostic significance of KRAS MASI was independent of clinical stage and was
      maintained among stage I patients. The detection of KRAS MASI in lung
      adenocarcinomas by sequencing electropherograms may identify patients with more
      aggressive disease.

PMID- 21743434
TI  - Increased gene copy number of ERG on chromosome 21 but not TMPRSS2-ERG fusion
      predicts outcome in prostatic adenocarcinomas.
AB  - The role of TMPRSS2-ERG gene fusion in prostate cancer prognostication remains
      controversial. We evaluated the prognostic role of TMPRSS2-ERG fusion using
      fluorescence in situ hybridization analysis in a case-control study nested in The
      Johns Hopkins retropubic radical prostatectomy cohort. In all, 10 tissue
      microarrays containing paired tumors and normal tissues obtained from 172 cases
      (recurrence) and 172 controls (non-recurrence) matched on pathological grade,
      stage, race/ethnicity, and age at the time of surgery were analyzed. All radical
      prostatectomies were performed at our institution between 1993 and 2004.
      Recurrence was defined as biochemical recurrence, development of clinical
      evidence of metastasis, or death from prostate carcinoma. Each tissue microarray
      spot was scored for the presence of TMPRSS2-ERG gene fusion and for ERG gene copy
      number gains. The odds ratio of recurrence and 95% confidence intervals were
      estimated from conditional logistic regression. Although the percentage of cases
      with fusion was slightly lower in cases than in controls (50 vs 57%), the
      difference was not statistically significant (P=0.20). The presence of fusion due
      to either deletion or split event was not associated with recurrence. Similarly,
      the presence of duplicated ERG deletion, duplicated ERG split, or ERG gene copy
      number gain with a single ERG fusion was not associated with recurrence. ERG gene
      polysomy without fusion was significantly associated with recurrence (odds ratio
      2.0, 95% confidence interval 1.17-3.42). In summary, TMPRSS2-ERG fusion was not
      prognostic for recurrence after retropubic radical prostatectomy for clinically
      localized prostate cancer, although men with ERG gene copy number gain without
      fusion were twice more likely to recur.

PMID- 21743435
TI  - VEGFA gene locus (6p12) amplification identifies a small but highly aggressive
      subgroup of colorectal cancer [corrected] patients.
AB  - The aim of this study was to determine: (1) the frequency of VEGFA gene locus
      (6p12) amplification in colorectal cancers, (2) the effect of gene amplification
      on clinical outcome using two independent colorectal cancer patient cohorts and
      (3) the relationship between amplification and KRAS or BRAF gene mutation as well
      as with other RAS/MAPK signalling proteins. Single-punch (n=1280; cohort 1) and
      multiple-punch (n=195; cohort 2) tissue microarrays were used for dual-labelling
      fluorescence in situ hybridization (FISH). Amplification was defined as a ratio
      >2 times for 6p12/centromere 6 signals. Mutation analysis of KRAS (codons 12 and
      13) and BRAF (codon V600E) and immunohistochemistry for p-MAPK3/MAPK1, PEBP1,
      HMMR, p-AKT, PLAU, PLAUR, TP53 and VEGFA were performed on cohort 1. In cohort 1,
      VEGFA amplification was found in 39/1280 (3%) cases and linked to higher pT stage
      (P=0.022), higher tumor grade (P=0.024) and vascular invasion (P=0.003). The 5
      year disease-specific survival rates were 31% (95% CI 17-46) and 57% (95% CI 54
      60) for amplified and nonamplified cases, respectively (P<0.001). Results were
      confirmed in cohort 2. In multivariable analysis, the relative risk for
      amplification was 2.09 (95% CI 1.4-3.1; P<0.001) and linked to more frequent BRAF
      mutation (P=0.015), overexpression of p-MAPK3/MAPK1 (P=0.012) and PLAU (P=0.048)
      and loss of metastasis suppressor protein PEBP1 (P=0.047). VEGFA gene locus
      amplification highlights a small but remarkably aggressive subgroup of colorectal
      cancers. Further studies are needed to elucidate the potential role of
      amplification as a prognostic or predictive biomarker in both metastatic and
      nonmetastatic patients.

PMID- 21743436
TI  - Molecular discrimination of cutaneous squamous cell carcinoma from actinic
      keratosis and normal skin.
AB  - Actinic keratosis is widely believed to be a neoplastic lesion and a precursor to
      invasive squamous cell carcinoma. However, there has been some debate as to
      whether actinic keratosis is in fact actually squamous cell carcinoma and should
      be treated as such. As the clinical management and prognosis of patients is
      widely held to be different for each of these lesions, our goal was to identify
      unique gene signatures using DNA microarrays to discriminate among normal skin,
      actinic keratosis, and squamous cell carcinoma, and examine the molecular
      pathways of carcinogenesis involved in the progression from normal skin to
      squamous cell carcinoma. Formalin-fixed and paraffin-embedded blocks of skin:
      five normal skins (pooled), six actinic keratoses, and six squamous cell
      carcinomas were retrieved. The RNA was extracted and amplified. The labeled
      targets were hybridized to the Affymetrix human U133plus2.0 array and the
      acquisition and initial quantification of array images were performed using the
      GCOS (Affymetrix). The subsequent data analyses were performed using DNA-Chip
      Analyzer and Partek Genomic Suite 6.4. Significant differential gene expression
      (>2 fold change, P<0.05) was seen with 382 differentially expressed genes between
      squamous cell carcinoma and normal skin, 423 differentially expressed genes
      between actinic keratosis and normal skin, and 9 differentially expressed genes
      between actinic keratosis and squamous cell carcinoma. The differentially
      expressed genes offer the possibility of using DNA microarrays as a molecular
      diagnostic tool to distinguish between normal skin, actinic keratosis, and
      squamous cell carcinoma. In addition, the differentially expressed genes and
      their molecular pathways could be potentially used as prognostic markers or
      targets for future therapeutic innovations.

PMID- 21743437
TI  - Control of Ubp3 ubiquitin protease activity by the Hog1 SAPK modulates
      transcription upon osmostress.
AB  - Protein ubiquitylation is a key process in the regulation of many cellular
      processes. The balance between the activity of ubiquitin ligases and that of
      proteases controls the level of ubiquitylation. In response to extracellular
      stimuli, stress-activated protein kinases (SAPK) modulate gene expression to
      maximize cell survival. In yeast, the Hog1 SAPK has a key role in reprogramming
      the gene expression pattern required for cell survival upon osmostress. Here, we
      show that the Ubp3 ubiquitin protease is a target for the Hog1 SAPK to modulate
      gene expression. ubp3 mutant cells are defective in expression of osmoresponsive
      genes. Hog1 interacts with and phosphorylates Ubp3 at serine 695, which is
      essential to determine the extent of transcriptional activation in response to
      osmostress. Furthermore, Ubp3 is recruited to osmoresponsive genes to modulate
      transcriptional initiation as well as elongation. Therefore, Ubp3 activity
      responds to external stimuli and is required for transcriptional activation upon
      osmostress.

PMID- 21743438
TI  - PICH and BLM limit histone association with anaphase centromeric DNA threads and
      promote their resolution.
AB  - Centromeres nucleate the formation of kinetochores and are vital for chromosome
      segregation during mitosis. The SNF2 family helicase PICH (Plk1-interacting
      checkpoint helicase) and the BLM (the Bloom's syndrome protein) helicase decorate
      ultrafine histone-negative DNA threads that link the segregating sister
      centromeres during anaphase. The functions of PICH and BLM at these threads are
      not understood, however. Here, we show that PICH binds to BLM and enables BLM
      localization to anaphase centromeric threads. PICH- or BLM-RNAi cells fail to
      resolve these threads in anaphase. The fragmented threads form centromeric
      chromatin-containing micronuclei in daughter cells. Anaphase threads in PICH- and
      BLM-RNAi cells contain histones and centromere markers. Recombinant purified PICH
      has nucleosome remodelling activities in vitro. We propose that PICH and BLM
      unravel centromeric chromatin and keep anaphase DNA threads mostly free of
      nucleosomes, thus allowing these threads to span long distances between rapidly
      segregating centromeres without breakage and providing a spatiotemporal window
      for their resolution.

PMID- 21743439
TI  - Misfolded PrP impairs the UPS by interaction with the 20S proteasome and
      inhibition of substrate entry.
AB  - Prion diseases are associated with the conversion of cellular prion protein
      (PrP(C)) to toxic beta-sheet isoforms (PrP(Sc)), which are reported to inhibit
      the ubiquitin-proteasome system (UPS). Accordingly, UPS substrates accumulate in
      prion-infected mouse brains, suggesting impairment of the 26S proteasome. A
      direct interaction between its 20S core particle and PrP isoforms was
      demonstrated by immunoprecipitation. beta-PrP aggregates associated with the 20S
      particle, but did not impede binding of the PA26 complex, suggesting that the
      aggregates do not bind to its ends. Aggregated beta-PrP reduced the 20S
      proteasome's basal peptidase activity, and the enhanced activity induced by C
      terminal peptides from the 19S ATPases or by the 19S regulator itself, including
      when stimulated by polyubiquitin conjugates. However, the 20S proteasome was not
      inhibited when the gate in the alpha-ring was open due to a truncation mutation
      or by association with PA26/PA28. These PrP aggregates inhibit by stabilising the
      closed conformation of the substrate entry channel. A similar inhibition of
      substrate entry into the proteasome may occur in other neurodegenerative diseases
      where misfolded beta-sheet-rich proteins accumulate.

PMID- 21743440
TI  - The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual
      dimorphism in fertility.
AB  - The cohesin complex is a ring-shaped proteinaceous structure that entraps the two
      sister chromatids after replication until the onset of anaphase when the ring is
      opened by proteolytic cleavage of its alpha-kleisin subunit (RAD21 at mitosis and
      REC8 at meiosis) by separase. RAD21L is a recently identified alpha-kleisin that
      is present from fish to mammals and biochemically interacts with the cohesin
      subunits SMC1, SMC3 and STAG3. RAD21L localizes along the axial elements of the
      synaptonemal complex of mouse meiocytes. However, its existence as a bona fide
      cohesin and its functional role awaits in vivo validation. Here, we show that
      male mice lacking RAD21L are defective in full synapsis of homologous chromosomes
      at meiotic prophase I, which provokes an arrest at zygotene and leads to total
      azoospermia and consequently infertility. In contrast, RAD21L-deficient females
      are fertile but develop an age-dependent sterility. Thus, our results provide in
      vivo evidence that RAD21L is essential for male fertility and in females for the
      maintenance of fertility during natural aging.

PMID- 21743441
TI  - Tdrd1 acts as a molecular scaffold for Piwi proteins and piRNA targets in
      zebrafish.
AB  - Piwi proteins function in an RNAi-like pathway that silences transposons. Piwi
      associated RNAs, also known as piRNAs, act as a guide to identify Piwi targets.
      The tudor domain-containing protein Tdrd1 has been linked to this pathway but its
      function has thus far remained unclear. We show that zebrafish Tdrd1 is required
      for efficient Piwi-pathway activity and proper nuage formation. Furthermore, we
      find that Tdrd1 binds both zebrafish Piwi proteins, Ziwi and Zili, and reveals
      sequence specificity in the interaction between Tdrd1 tudor domains and
      symmetrically dimethylated arginines (sDMAs) in Zili. Finally, we show that Tdrd1
      complexes contain piRNAs and RNA molecules that are longer than piRNAs. We name
      these longer transcripts Tdrd1-associated transcripts (TATs). TATs likely
      represent cleaved Piwi pathway targets and may serve as piRNA biogenesis
      intermediates. Altogether, our data suggest that Tdrd1 acts as a molecular
      scaffold for Piwi proteins, bound through specific tudor domain-sDMA
      interactions, piRNAs and piRNA targets.

PMID- 21743442
TI  - Prostate cancer: Abiraterone increases overall survival in men with castration
      resistant prostate cancer.

PMID- 21743443
TI  - Pain: MRI reveals altered brain activity and anatomy in men with CP/CPPS.

PMID- 21743445
TI  - Kidney cancer: Incorporating new parameters into pathological staging of RCC.

PMID- 21743446
TI  - Bladder cancer: Time to embrace neoadjuvant chemotherapy for invasive disease.

PMID- 21743447
TI  - Surgery: Robotic prostatectomy proven to provide sexual outcome benefit.

PMID- 21743448
TI  - Stones: can the Guy's stone score predict PNL outcomes?

PMID- 21743449
TI  - Graphene: The long and winding road.

PMID- 21743450
TI  - A fast, high-endurance and scalable non-volatile memory device made from
      asymmetric Ta2O(5-x)/TaO(2-x) bilayer structures.
AB  - Numerous candidates attempting to replace Si-based flash memory have failed for a
      variety of reasons over the years. Oxide-based resistance memory and the related
      memristor have succeeded in surpassing the specifications for a number of device
      requirements. However, a material or device structure that satisfies high
      density, switching-speed, endurance, retention and most importantly power
      consumption criteria has yet to be announced. In this work we demonstrate a
      TaO(x)-based asymmetric passive switching device with which we were able to
      localize resistance switching and satisfy all aforementioned requirements. In
      particular, the reduction of switching current drastically reduces power
      consumption and results in extreme cycling endurances of over 10(12). Along with
      the 10 ns switching times, this allows for possible applications to the working
      memory space as well. Furthermore, by combining two such devices each with an
      intrinsic Schottky barrier we eliminate any need for a discrete transistor or
      diode in solving issues of stray leakage current paths in high-density crossbar
      arrays.

PMID- 21743451
TI  - Face-selective electrostatic control of hydrothermal zinc oxide nanowire
      synthesis.
AB  - Rational control over the morphology and the functional properties of inorganic
      nanostructures has been a long-standing goal in the development of bottom-up
      device fabrication processes. We report that the geometry of hydrothermally grown
      zinc oxide nanowires can be tuned from platelets to needles, covering more than
      three orders of magnitude in aspect ratio (~0.1-100). We introduce a classical
      thermodynamics-based model to explain the underlying growth inhibition mechanism
      by means of the competitive and face-selective electrostatic adsorption of non
      zinc complex ions at alkaline conditions. The performance of these nanowires
      rivals that of vapour-phase-grown nanostructures, and their low-temperature
      synthesis (<60  degrees C) is favourable to the integration and in situ
      fabrication of complex and polymer-supported devices. We illustrate this
      capability by fabricating an all-inorganic light-emitting diode in a polymeric
      microfluidic manifold. Our findings indicate that electrostatic interactions in
      aqueous crystal growth may be systematically manipulated to synthesize
      nanostructures and devices with enhanced structural control.

PMID- 21743452
TI  - Imaging the subcellular structure of human coronary atherosclerosis using micro
      optical coherence tomography.
AB  - Progress in understanding, diagnosis, and treatment of coronary artery disease
      (CAD) has been hindered by our inability to observe cells and extracellular
      components associated with human coronary atherosclerosis in situ. The current
      standards for microstructural investigation, histology and electron microscopy
      are destructive and prone to artifacts. The highest-resolution intracoronary
      imaging modality, optical coherence tomography (OCT), has a resolution of ~10
      MUm, which is too coarse for visualizing most cells. Here we report a new form of
      OCT, termed micro-optical coherence tomography (MUOCT), whose resolution is
      improved by an order of magnitude. We show that MUOCT images of cadaver coronary
      arteries provide clear pictures of cellular and subcellular features associated
      with atherogenesis, thrombosis and responses to interventional therapy. These
      results suggest that MUOCT can complement existing diagnostic techniques for
      investigating atherosclerotic specimens, and that MUOCT may eventually become a
      useful tool for cellular and subcellular characterization of the human coronary
      wall in vivo.

PMID- 21743453
TI  - Carvedilol and its new analogs suppress arrhythmogenic store overload-induced
      Ca2+ release.
AB  - Carvedilol is one of the most effective beta blockers for preventing ventricular
      tachyarrhythmias in heart failure, but the mechanisms underlying its favorable
      antiarrhythmic benefits remain unclear. Spontaneous Ca(2+) waves, also called
      store overload-induced Ca(2+) release (SOICR), evoke ventricular tachyarrhythmias
      in individuals with heart failure. Here we show that carvedilol is the only beta
      blocker tested that effectively suppresses SOICR by directly reducing the open
      duration of the cardiac ryanodine receptor (RyR2). This unique anti-SOICR
      activity of carvedilol, combined with its beta-blocking activity, probably
      contributes to its favorable antiarrhythmic effect. To enable optimal titration
      of carvedilol's actions as a beta blocker and as a suppressor of SOICR
      separately, we developed a new SOICR-inhibiting, minimally beta-blocking
      carvedilol analog, VK-II-86. VK-II-86 prevented stress-induced ventricular
      tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined
      with either of the selective beta blockers metoprolol or bisoprolol. Combining
      SOICR inhibition with optimal beta blockade has the potential to provide
      antiarrhythmic therapy that can be tailored to individual patients.

PMID- 21743454
TI  - DNA-based programming of quantum dot valency, self-assembly and luminescence.
AB  - The electronic and optical properties of colloidal quantum dots, including the
      wavelengths of light that they can absorb and emit, depend on the size of the
      quantum dots. These properties have been exploited in a number of applications
      including optical detection, solar energy harvesting and biological research.
      Here, we report the self-assembly of quantum dot complexes using cadmium
      telluride nanocrystals capped with specific sequences of DNA. Quantum dots with
      between one and five DNA-based binding sites are synthesized and then used as
      building blocks to create a variety of rationally designed assemblies, including
      cross-shaped complexes containing three different types of dots. The structure of
      the complexes is confirmed with transmission electron microscopy, and
      photophysical studies are used to quantify energy transfer among the constituent
      components. Through changes in pH, the conformation of the complexes can also be
      reversibly switched, turning on and off the transfer of energy between the
      constituent quantum dots.

PMID- 21743455
TI  - Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1.
AB  - Wnt morphogens control embryonic development and homeostasis in adult tissues. In
      vertebrates the N-terminal WIF domain (WIF-1(WD)) of Wnt inhibitory factor 1 (WIF
      1) binds Wnt ligands. Our crystal structure of WIF-1(WD) reveals a previously
      unidentified binding site for phospholipid; two acyl chains extend deep into the
      domain, and the head group is exposed to the surface. Biophysical and cellular
      assays indicate that there is a WIF-1(WD) Wnt-binding surface proximal to the
      lipid head group but also implicate the five epidermal growth factor (EGF)-like
      domains (EGFs I-V) in Wnt binding. The six-domain WIF-1 crystal structure shows
      that EGFs I-V are wrapped back, interfacing with WIF-1(WD) at EGF III. EGFs II-V
      contain a heparan sulfate proteoglycan (HSPG)-binding site, consistent with
      conserved positively charged residues on EGF IV. This combination of HSPG- and
      Wnt-binding properties suggests a modular model for the localization of WIF-1 and
      for signal inhibition within morphogen gradients.

PMID- 21743456
TI  - Pinkbar is an epithelial-specific BAR domain protein that generates planar
      membrane structures.
AB  - Bin/amphipysin/Rvs (BAR)-domain proteins sculpt cellular membranes and have key
      roles in processes such as endocytosis, cell motility and morphogenesis. BAR
      domains are divided into three subfamilies: BAR- and F-BAR-domain proteins
      generate positive membrane curvature and stabilize cellular invaginations,
      whereas I-BAR-domain proteins induce negative curvature and stabilize
      protrusions. We show that a previously uncharacterized member of the I-BAR
      subfamily, Pinkbar, is specifically expressed in intestinal epithelial cells,
      where it localizes to Rab13-positive vesicles and to the plasma membrane at
      intercellular junctions. Notably, the BAR domain of Pinkbar does not induce
      membrane tubulation but promotes the formation of planar membrane sheets.
      Structural and mutagenesis analyses reveal that the BAR domain of Pinkbar has a
      relatively flat lipid-binding interface and that it assembles into sheet-like
      oligomers in crystals and in solution, which may explain its unique membrane
      deforming activity.

PMID- 21743457
TI  - SUMOylation regulates telomere length homeostasis by targeting Cdc13.
AB  - Telomere length homeostasis is an important aspect of telomere biology. Here, we
      show that SUMOylation limits telomere length and targets multiple telomere
      proteins in Saccharomyces cerevisiae. A main target is Cdc13, which both
      positively and negatively regulates telomerase and confers end protection. We
      demonstrate that Cdc13 SUMOylation restrains telomerase functions by promoting
      Cdc13 interaction with the telomerase inhibitor Stn1 without affecting end
      protection. Mutation of the Cdc13 SUMOylation site (cdc13-snm) lengthens
      telomeres and reduces the Stn1 interaction, whereas Cdc13-SUMO fusion has the
      opposite effects. cdc13-snm's effect on telomere length is epistatic with stn1,
      but not with yku70, tel1 or est1 alleles, and is suppressed by Stn1
      overexpression. Cdc13 SUMOylation peaks in early-mid S phase, prior to its known
      Cdk1-mediated phosphorylation, and the two modifications act antagonistically,
      suggesting that the opposite roles of Cdc13 in telomerase regulation can be
      separated temporally and regulated by distinct modifications.

PMID- 21743458
TI  - Dimerization of Plasmodium vivax DBP is induced upon receptor binding and drives
      recognition of DARC.
AB  - Plasmodium vivax and Plasmodium knowlesi invasion depends on the parasite Duffy
      binding protein DBL domain (RII-PvDBP or RII-PkDBP) engaging the Duffy antigen
      receptor for chemokines (DARC) on red blood cells. Inhibition of this key
      interaction provides an excellent opportunity for parasite control. There are
      competing models for whether Plasmodium ligands engage receptors as monomers or
      dimers, a question whose resolution has profound implications for parasite
      biology and control. We report crystallographic, solution and functional studies
      of RII-PvDBP showing that dimerization is required for and driven by receptor
      engagement. This work provides a unifying framework for prior studies and
      accounts for the action of naturally acquired blocking antibodies and the
      mechanism of immune evasion. We show that dimerization is conserved in DBL-domain
      receptor engagement and propose that receptor-mediated ligand dimerization drives
      receptor affinity and specificity. Because dimerization is prevalent in
      signaling, our studies raise the possibility that induced dimerization may
      activate pathways for invasion.

PMID- 21743459
TI  - Large-scale phosphosite quantification in tissues by a spike-in SILAC method.
AB  - Despite progress in mass spectrometry (MS)-based phosphoproteomics, large-scale
      in vivo analyses remain challenging. Here we report a 'spike-in' stable-isotope
      labeling with amino acids in cell culture (SILAC) methodology using standards
      derived from labeled mouse liver cell lines, using which we analyzed insulin
      signaling. With this approach we identified 15,000 phosphosites and
      quantitatively compared 10,000 sites in response to insulin treatment, creating a
      very large, accurately quantified in vivo phosphoproteome dataset.

PMID- 21743460
TI  - Protein standard absolute quantification (PSAQ) method for the measurement of
      cellular ubiquitin pools.
AB  - The protein ubiquitin is an important post-translational modifier that regulates
      a wide variety of biological processes. In cells, ubiquitin is apportioned among
      distinct pools, which include a variety of free and conjugated species. Although
      maintenance of a dynamic and complex equilibrium among ubiquitin pools is crucial
      for cell survival, the tools necessary to quantify each cellular ubiquitin pool
      have been limited. We have developed a quantitative mass spectrometry approach to
      measure cellular concentrations of ubiquitin species using isotope-labeled
      protein standards and applied it to characterize ubiquitin pools in cells and
      tissues. Our method is convenient, adaptable and should be a valuable tool to
      facilitate our understanding of this important signaling molecule.

PMID- 21743461
TI  - Tracking genome engineering outcome at individual DNA breakpoints.
AB  - Site-specific genome engineering technologies are increasingly important tools in
      the postgenomic era, where biotechnological objectives often require organisms
      with precisely modified genomes. Rare-cutting endonucleases, through their
      capacity to create a targeted DNA strand break, are one of the most promising of
      these technologies. However, realizing the full potential of nuclease-induced
      genome engineering requires a detailed understanding of the variables that
      influence resolution of nuclease-induced DNA breaks. Here we present a genome
      engineering reporter system, designated 'traffic light', that supports rapid flow
      cytometric analysis of repair pathway choice at individual DNA breaks,
      quantitative tracking of nuclease expression and donor template delivery, and
      high-throughput screens for factors that bias the engineering outcome. We applied
      the traffic light system to evaluate the efficiency and outcome of nuclease
      induced genome engineering in human cell lines and identified strategies to
      facilitate isolation of cells in which a desired engineering outcome has
      occurred.

PMID- 21743462
TI  - A chemical probe selectively inhibits G9a and GLP methyltransferase activity in
      cells.
AB  - Protein lysine methyltransferases G9a and GLP modulate the transcriptional
      repression of a variety of genes via dimethylation of Lys9 on histone H3
      (H3K9me2) as well as dimethylation of non-histone targets. Here we report the
      discovery of UNC0638, an inhibitor of G9a and GLP with excellent potency and
      selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638
      treatment of a variety of cell lines resulted in lower global H3K9me2 levels,
      equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with
      the functional potency of UNC0638 being well separated from its toxicity. UNC0638
      markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of
      H3K9me2 marks at promoters of known G9a-regulated endogenous genes and
      disproportionately affected several genomic loci encoding microRNAs. In mouse
      embryonic stem cells, UNC0638 reactivated G9a-silenced genes and a retroviral
      reporter gene in a concentration-dependent manner without promoting
      differentiation.

PMID- 21743463
TI  - Cleavage of cohesin rings coordinates the separation of centrioles and
      chromatids.
AB  - Cohesin pairs sister chromatids by forming a tripartite Scc1-Smc1-Smc3 ring
      around them. In mitosis, cohesin is removed from chromosome arms by the
      phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by
      shugoshin 1 and protein phosphatase 2A (Sgo1-PP2A) and opened only in anaphase by
      separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation,
      centrioles loosen their tight orthogonal arrangement, which licenses later
      centrosome duplication in S phase. Although a role of separase in centriole
      disengagement has been reported, the molecular details of this process remain
      enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both
      premature sister-chromatid separation and centriole disengagement are induced by
      ectopic activation of separase or depletion of Sgo1. These unscheduled events are
      suppressed by expression of non-cleavable Scc1 or inhibition of the prophase
      pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the
      corresponding site-specific protease triggers centriole disengagement. Separation
      of centrioles can alternatively be induced by ectopic cleavage of an engineered
      Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and
      are coordinated with each other by dual use of the cohesin ring complex.

PMID- 21743464
TI  - Mitotic internalization of planar cell polarity proteins preserves tissue
      polarity.
AB  - Planar cell polarity (PCP) is the collective polarization of cells along the
      epithelial plane, a process best understood in the terminally differentiated
      Drosophila wing. Proliferative tissues such as mammalian skin also show PCP, but
      the mechanisms that preserve tissue polarity during proliferation are not
      understood. During mitosis, asymmetrically distributed PCP components risk
      mislocalization or unequal inheritance, which could have profound consequences
      for the long-range propagation of polarity. Here, we show that when mouse
      epidermal basal progenitors divide PCP components are selectively internalized
      into endosomes, which are inherited equally by daughter cells. Following mitosis,
      PCP proteins are recycled to the cell surface, where asymmetry is re-established
      by a process reliant on neighbouring PCP. A cytoplasmic dileucine motif governs
      mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and
      Fzd6 to endosomes. Moreover, embryos transgenic for a Celsr1 that cannot
      mitotically internalize exhibit perturbed hair-follicle angling, a hallmark of
      defective PCP. This underscores the physiological relevance and importance of
      this mechanism for regulating polarity during cell division.

PMID- 21743465
TI  - Cdk1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation and
      chromosomal instability.
AB  - Aneuploidy and chromosomal instability are major characteristics of human cancer.
      These abnormalities can result from defects in the spindle assembly checkpoint
      (SAC), which is a surveillance mechanism for accurate chromosome segregation
      through restraint of the activity of the anaphase-promoting complex/cyclosome
      (APC/C). Here, we show that a CUE-domain-containing protein, CUEDC2, is a cell
      cycle regulator that promotes spindle checkpoint inactivation and releases APC/C
      from checkpoint inhibition. CUEDC2 is phosphorylated by Cdk1 during mitosis.
      Depletion of CUEDC2 causes a checkpoint-dependent delay of the metaphase-anaphase
      transition. Phosphorylated CUEDC2 binds to Cdc20, an activator of APC/C, and
      promotes the release of Mad2 from APC/C-Cdc20 and subsequent APC/C activation.
      CUEDC2 overexpression causes earlier activation of APC/C, leading to chromosome
      missegregation and aneuploidy. Interestingly, CUEDC2 is highly expressed in many
      types of tumours. These results suggest that CUEDC2 is a key regulator of mitosis
      progression, and that CUEDC2 dysregulation might contribute to tumour development
      by causing chromosomal instability.

PMID- 21743466
TI  - Mir193b-365 is essential for brown fat differentiation.
AB  - Mammals have two principal types of fat. White adipose tissue primarily serves to
      store extra energy as triglycerides, whereas brown adipose tissue is specialized
      to burn lipids for heat generation and energy expenditure as a defence against
      cold and obesity. Recent studies have demonstrated that brown adipocytes arise in
      vivo from a Myf5-positive, myoblastic progenitor by the action of Prdm16 (PR
      domain containing 16). Here, we identified a brown-fat-enriched miRNA cluster,
      MiR-193b-365, as a key regulator of brown fat development. Blocking miR-193b
      and/or miR-365 in primary brown preadipocytes markedly impaired brown adipocyte
      adipogenesis by enhancing Runx1t1 (runt-related transcription factor 1;
      translocated to, 1) expression, whereas myogenic markers were significantly
      induced. Forced expression of Mir193b and/or Mir365 in C2C12 myoblasts blocked
      the entire programme of myogenesis, and, in adipogenic conditions, miR-193b
      induced myoblasts to differentiate into brown adipocytes. Mir193b-365 was
      upregulated by Prdm16 partially through Pparalpha. Our results demonstrate that
      Mir193b-365 serves as an essential regulator for brown fat differentiation, in
      part by repressing myogenesis.

PMID- 21743467
TI  - Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide
      association study.
AB  - Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed
      countries. We conducted a multi-stage genome-wide association study for PrCa and
      previously reported the results of the first two stages, which identified 16 PrCa
      susceptibility loci. We report here the results of stage 3, in which we evaluated
      1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls.
      We followed up ten new association signals through genotyping in 51,311 samples
      in 30 studies from the Prostate Cancer Association Group to Investigate Cancer
      Associated Alterations in the Genome (PRACTICAL) consortium. In addition to
      replicating previously reported loci, we identified seven new prostate cancer
      susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12
      (P = 4.0 * 10(-8) to P = 2.7 * 10(-24)). We also identified a SNP in TERT more
      strongly associated with PrCa than that previously reported. More than 40 PrCa
      susceptibility loci, explaining ~25% of the familial risk in this disease, have
      now been identified.

PMID- 21743468
TI  - Increased exonic de novo mutation rate in individuals with schizophrenia.
AB  - Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive,
      behavioral and emotional processes. The wide spectrum of symptoms and clinical
      variability in schizophrenia suggest a complex genetic etiology, which is
      consistent with the numerous loci thus far identified by linkage, copy number
      variation and association studies. Although schizophrenia heritability may be as
      high as ~80%, the genes responsible for much of this heritability remain to be
      identified. Here we sequenced the exomes of 14 schizophrenia probands and their
      parents. We identified 15 de novo mutations (DNMs) in eight probands, which is
      significantly more than expected considering the previously reported DNM rate. In
      addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than
      what is expected by chance. Our study supports the notion that DNMs may account
      for some of the heritability reported for schizophrenia while providing a list of
      genes possibly involved in disease pathogenesis.

PMID- 21743469
TI  - Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates
      peptide handling in the mechanism for HLA-B27 in disease susceptibility.
AB  - Ankylosing spondylitis is a common form of inflammatory arthritis predominantly
      affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults
      of European descent. Here we report the identification of three variants in the
      RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing
      spondylitis (P < 5 * 10(-8) in the combined discovery and replication datasets)
      and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong
      association across all our datasets (P < 5 * 10(-6) overall, with support in each
      of the three datasets studied). We also show that polymorphisms of ERAP1, which
      encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming
      before HLA class I presentation, only affect ankylosing spondylitis risk in HLA
      B27-positive individuals. These findings provide strong evidence that HLA-B27
      operates in ankylosing spondylitis through a mechanism involving aberrant
      processing of antigenic peptides.

PMID- 21743470
TI  - Cocaine supersensitivity and enhanced motivation for reward in mice lacking
      dopamine D2 autoreceptors.
AB  - Dopamine (DA) D2 receptors expressed in DA neurons (D2 autoreceptors) exert a
      negative feedback regulation that reduces DA neuron firing, DA synthesis and DA
      release. As D2 receptors are mostly expressed in postsynaptic neurons,
      pharmacological and genetic approaches have been unable to definitively address
      the in vivo contribution of D2 autoreceptors to DA-mediated behaviors. We found
      that midbrain DA neurons from mice deficient in D2 autoreceptors
      (Drd2(loxP/loxP); Dat(+/IRES-cre), referred to as autoDrd2KO mice) lacked DA
      mediated somatodendritic synaptic responses and inhibition of DA release.
      AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and
      supersensitivity to the psychomotor effects of cocaine. The mice also exhibited
      increased place preference for cocaine and enhanced motivation for food reward.
      Our results highlight the importance of D2 autoreceptors in the regulation of DA
      neurotransmission and demonstrate that D2 autoreceptors are important for normal
      motor function, food-seeking behavior, and sensitivity to the locomotor and
      rewarding properties of cocaine.

PMID- 21743471
TI  - Neurod6 expression defines new retinal amacrine cell subtypes and regulates their
      fate.
AB  - Most regions of the CNS contain many subtypes of inhibitory interneurons with
      specialized roles in circuit function. In the mammalian retina, the ~30 subtypes
      of inhibitory interneurons called amacrine cells (ACs) are generally divided into
      two groups: wide/medium-field GABAergic ACs and narrow-field glycinergic ACs,
      which mediate lateral and vertical interactions, respectively, within the inner
      plexiform layer. We used expression profiling and mouse transgenic lines to
      identify and characterize two closely related narrow-field AC subtypes. Both
      arise postnatally and one is neither glycinergic nor GABAergic (nGnG). Two
      transcription factors selectively expressed by these subtypes, Neurod6 and
      special AT-rich-sequence-binding protein 2 (Satb2), regulate a postmitotic cell
      fate choice between these subtypes. Satb2 induces Neurod6, which persists in nGnG
      ACs and promotes their fate but is downregulated in the related glycinergic AC
      subtype. Our results support the view that cell fate decisions made in
      progenitors and their progeny act together to diversify ACs.

PMID- 21743472
TI  - High-accuracy neurite reconstruction for high-throughput neuroanatomy.
AB  - Neuroanatomic analysis depends on the reconstruction of complete cell shapes.
      High-throughput reconstruction of neural circuits, or connectomics, using volume
      electron microscopy requires dense staining of all cells, which leads even
      experts to make annotation errors. Currently, reconstruction speed rather than
      acquisition speed limits the determination of neural wiring diagrams. We
      developed a method for fast and reliable reconstruction of densely labeled data
      sets. Our approach, based on manually skeletonizing each neurite redundantly
      (multiple times) with a visualization-annotation software tool called KNOSSOS, is
      ~50-fold faster than volume labeling. Errors are detected and eliminated by a
      redundant-skeleton consensus procedure (RESCOP), which uses a statistical model
      of how true neurite connectivity is transformed into annotation decisions. RESCOP
      also estimates the reliability of consensus skeletons. Focused reannotation of
      difficult locations promises a rather steep increase of reliability as a function
      of the average skeleton redundancy and thus the nearly error-free analysis of
      large neuroanatomical datasets.

PMID- 21743473
TI  - Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in
      vivo.
AB  - Multiphoton imaging (MPI) is widely used for recording activity simultaneously
      from many neurons in superficial cortical layers in vivo. We combined
      regenerative amplification multiphoton microscopy (RAMM) with genetically encoded
      calcium indicators to extend MPI of neuronal population activity into layer 5
      (L5) of adult mouse somatosensory cortex. We found that this approach could be
      used to record and quantify spontaneous and sensory-evoked activity in
      populations of L5 neuronal somata located as much as 800 MUm below the pia. In
      addition, we found that RAMM could be used to simultaneously image activity from
      large (80) populations of apical dendrites and follow these dendrites down to
      their somata of origin.

PMID- 21743475
TI  - Protein targeting and degradation are coupled for elimination of mislocalized
      proteins.
AB  - A substantial proportion of the genome encodes membrane proteins that are
      delivered to the endoplasmic reticulum by dedicated targeting pathways. Membrane
      proteins that fail targeting must be rapidly degraded to avoid aggregation and
      disruption of cytosolic protein homeostasis. The mechanisms of mislocalized
      protein (MLP) degradation are unknown. Here we reconstitute MLP degradation in
      vitro to identify factors involved in this pathway. We find that nascent membrane
      proteins tethered to ribosomes are not substrates for ubiquitination unless they
      are released into the cytosol. Their inappropriate release results in capture by
      the Bag6 complex, a recently identified ribosome-associating chaperone. Bag6
      complex-mediated capture depends on the presence of unprocessed or non-inserted
      hydrophobic domains that distinguish MLPs from potential cytosolic proteins. A
      subset of these Bag6 complex 'clients' are transferred to TRC40 for insertion
      into the membrane, whereas the remainder are rapidly ubiquitinated. Depletion of
      the Bag6 complex selectively impairs the efficient ubiquitination of MLPs. Thus,
      by its presence on ribosomes that are synthesizing nascent membrane proteins, the
      Bag6 complex links targeting and ubiquitination pathways. We propose that such
      coupling allows the fast tracking of MLPs for degradation without futile
      engagement of the cytosolic folding machinery.

PMID- 21743474
TI  - Genome sequence and analysis of the tuber crop potato.
AB  - Potato (Solanum tuberosum L.) is the world's most important non-grain food crop
      and is central to global food security. It is clonally propagated, highly
      heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we
      use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of
      the 844-megabase genome. We predict 39,031 protein-coding genes and present
      evidence for at least two genome duplication events indicative of a
      palaeopolyploid origin. As the first genome sequence of an asterid, the potato
      genome reveals 2,642 genes specific to this large angiosperm clade. We also
      sequenced a heterozygous diploid clone and show that gene presence/absence
      variants and other potentially deleterious mutations occur frequently and are a
      likely cause of inbreeding depression. Gene family expansion, tissue-specific
      expression and recruitment of genes to new pathways contributed to the evolution
      of tuber development. The potato genome sequence provides a platform for genetic
      improvement of this vital crop.

PMID- 21743476
TI  - Crystal structure of the human centromeric nucleosome containing CENP-A.
AB  - In eukaryotes, accurate chromosome segregation during mitosis and meiosis is
      coordinated by kinetochores, which are unique chromosomal sites for microtubule
      attachment. Centromeres specify the kinetochore formation sites on individual
      chromosomes, and are epigenetically marked by the assembly of nucleosomes
      containing the centromere-specific histone H3 variant, CENP-A. Although the
      underlying mechanism is unclear, centromere inheritance is probably dictated by
      the architecture of the centromeric nucleosome. Here we report the crystal
      structure of the human centromeric nucleosome containing CENP-A and its cognate
      alpha-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome,
      the DNA is wrapped around the histone octamer, consisting of two each of histones
      H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the
      canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible.
      The thirteen base pairs from both ends of the DNA are invisible in the crystal
      structure, and the alphaN helix of CENP-A is shorter than that of H3, which is
      known to be important for the orientation of the DNA ends in the canonical H3
      nucleosome. A structural comparison of the CENP-A and H3 nucleosomes revealed
      that CENP-A contains two extra amino acid residues (Arg 80 and Gly 81) in the
      loop 1 region, which is completely exposed to the solvent. Mutations of the CENP
      A loop 1 residues reduced CENP-A retention at the centromeres in human cells.
      Therefore, the CENP-A loop 1 may function in stabilizing the centromeric
      chromatin containing CENP-A, possibly by providing a binding site for trans
      acting factors. The structure provides the first atomic-resolution picture of the
      centromere-specific nucleosome.

PMID- 21743477
TI  - The crystal structure of a voltage-gated sodium channel.
AB  - Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable
      cells and are the molecular targets for drugs and disease mutations, but the
      structural basis for their voltage-dependent activation, ion selectivity and drug
      block is unknown. Here we report the crystal structure of a voltage-gated Na(+)
      channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation
      with four activated voltage sensors at 2.7 A resolution. The arginine gating
      charges make multiple hydrophilic interactions within the voltage sensor,
      including unanticipated hydrogen bonds to the protein backbone. Comparisons to
      previous open-pore potassium channel structures indicate that the voltage-sensor
      domains and the S4-S5 linkers dilate the central pore by pivoting together around
      a hinge at the base of the pore module. The NavAb selectivity filter is short,
      ~4.6 A wide, and water filled, with four acidic side chains surrounding the
      narrowest part of the ion conduction pathway. This unique structure presents a
      high-field-strength anionic coordination site, which confers Na(+) selectivity
      through partial dehydration via direct interaction with glutamate side chains.
      Fenestrations in the sides of the pore module are unexpectedly penetrated by
      fatty acyl chains that extend into the central cavity, and these portals are
      large enough for the entry of small, hydrophobic pore-blocking drugs. This
      structure provides the template for understanding electrical signalling in
      excitable cells and the actions of drugs used for pain, epilepsy and cardiac
      arrhythmia at the atomic level.

PMID- 21743478
TI  - Systems biology of vaccination for seasonal influenza in humans.
AB  - Here we have used a systems biology approach to study innate and adaptive
      responses to vaccination against influenza in humans during three consecutive
      influenza seasons. We studied healthy adults vaccinated with trivalent
      inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV).
      TIV induced higher antibody titers and more plasmablasts than LAIV did. In
      subjects vaccinated with TIV, early molecular signatures correlated with and
      could be used to accurately predict later antibody titers in two independent
      trials. Notably, expression of the kinase CaMKIV at day 3 was inversely
      correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with
      TIV induced enhanced antigen-specific antibody titers, which demonstrated an
      unappreciated role for CaMKIV in the regulation of antibody responses. Thus,
      systems approaches can be used to predict immunogenicity and provide new
      mechanistic insights about vaccines.

PMID- 21743479
TI  - Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and
      type I interferon-mediated immunity.
AB  - Toll-like receptors (TLRs) shape innate and adaptive immunity to microorganisms.
      The enzyme IRAK1 transduces signals from TLRs, but mechanisms for its activation
      and regulation remain unknown. We found here that TLR7 and TLR9 activated the
      isomerase Pin1, which then bound to IRAK1; this resulted in activation of IRAK1
      and facilitated its release from the receptor complex to activate the
      transcription factor IRF7 and induce type I interferons. Consequently, Pin1
      deficient cells and mice failed to mount TLR-mediated, interferon-dependent
      innate and adaptive immune responses. Given the critical role of aberrant
      activation of IRAK1 and type I interferons in various immune diseases,
      controlling IRAK1 activation via inhibition of Pin1 may represent a useful
      therapeutic approach.

PMID- 21743480
TI  - Green death: revealing programmed cell death in plants.

PMID- 21743481
TI  - Green spermatozoa illuminate a 30-year-old model: sperm-egg adhesion involves
      intra-acrosomal proteins.

PMID- 21743482
TI  - Long-term results of the surgical treatment of Peyronie's disease with Egydio's
      technique: a European multicentre study.
AB  - The long-term outcomes of 157 patients affected by Peyronie's disease (PD) who
      underwent penile straightening with Egydio's technique between January 2004 and
      December 2008 are reported. Only patients with PD who were stable for at least 6
      12 months prior to surgery were enrolled in this study. Preoperative assessment
      included a dynamic echo colour Doppler ultrasound scan to evaluate the degree of
      penile deformity and the peak systolic velocity in the cavernosal arteries and an
      assessment of erectile function with the administration of the International
      Index of Erectile Function 5 (IIEF-5) questionnaire. Stretched penile length was
      recorded pre- and postoperatively. Surgical complications, cosmesis and sexual
      function, patient satisfaction and postoperative erectile function were assessed
      postoperatively at 3 months, 1 year and 2 years, respectively. After a median
      follow-up period of 20 months (range: 12-24 months), we found that mild residual
      curvature (12%) and glans hypoesthesia (3%) were the only causes of partial
      dissatisfaction. No rejection of the graft was observed. All patients recovered
      their ability to penetrate with no difficulty. In addition, an intraoperative
      average increase of 2.5 cm (range: 1.7-4.1 cm) in stretched penile length was
      recorded, with all patients engaging in penetrative sexual intercourse. In
      conclusion, this procedure represents a safe and reproducible technique for the
      correction of penile curvature resulting from PD and yields excellent cosmetic
      and functional results.

PMID- 21743483
TI  - Abiraterone acetate for prostate cancer: a new era of hormonal therapies.

PMID- 21743484
TI  - Investigation and management of Toxoplasma gondii infection in pregnancy and
      infancy: a prospective study.
AB  - AIM: Toxoplasma gondii infection during pregnancy poses a serious risk to the
      fetus, therefore timely and accurate diagnosis is essential. The aim of this
      study was to estimate the frequency of congenital infection via evaluating
      mother's immunological status and the possibility to improving the diagnostic and
      therapeutic approaches. METHODS: Eighty five mothers with Toxoplasma
      seroconversion and their offspring were enrolled (among them, 2 spontaneous
      abortions were documented in the first trimester). Prenatal PCR diagnosis was
      carried out on 50 patients (60%), with 7 positive cases (14%). Morphological
      ultrasound scanning revealed anomalies in one fetus. Long-term follow-up included
      general physical examinations, serological status tested using Western blot,
      neuro-radiological, ophthalmologic and neurologic examinations, psychological and
      developmental tests, visual evoked potential tests and audiology tests, as well
      as anti-Toxoplasma treatment regimes. RESULTS: Fourteen (17%) of the infants were
      infected at one-year serological follow-up. Chi-square for linear trend of
      vertical transmission from the first to the third trimester was significant
      (P=0.009). Western blot analysis showed IgM and IgA in half of the infected
      infants. In 69 uninfected infants, anti-Toxoplasma IgG immunoblot analysis
      excluded infection within the 3 months in 18 infants (26%) and in the others
      within 6 months of life. The most relevant instrumental findings are described.
      CONCLUSION: Western blot analysis may help to evaluate infection within the 6
      months of life. The accuracy of ultrasound imaging to determine the brain damage
      in the fetus and newborns is doubtful, and should be combined with MR imaging.
      Multistep approaches can improve the timing of postnatal follow-up.

PMID- 21743485
TI  - Gold nanoparticles in cancer therapy.
AB  - The rapid advancement of nanotechnology in recent years has fuelled a burgeoning
      interest in the field of nanoparticle research, in particular, its application in
      the medical arena. A constantly expanding knowledge based on a better
      understanding of the properties of gold nanoparticles (AuNPs) coupled with
      relentless experimentation means that the frontiers of nanotechnology are
      constantly being challenged. At present, there seems to be heightened interest in
      the application of AuNPs to the management of cancer, encompassing diagnosis,
      monitoring and treatment of the disease. These efforts are undertaken in the hope
      of revolutionizing current methods of treatment and treatment strategies for a
      multifactorial disease such as cancer. This review will focus on the current
      applications of AuNPs in cancer management.

PMID- 21743486
TI  - Involvement of RhoA/ROCK in myocardial fibrosis in a rat model of type 2
      diabetes.
AB  - AIM: To investigate whether activation of RhoA/Rho kinase (ROCK) is involved in
      myocardial fibrosis in diabetic hearts. METHODS: A rat model of type 2 diabetes
      was established using high fat diet combined with streptozotocin (30 mg/kg, ip).
      Animals were randomly divided into 3 groups: control rats, untreated diabetic
      rats that received vehicle and treated diabetic rats that received Rho-kinase
      inhibitor fasudil hydrochloride hydrate (10 mg.kg(-1).d(-1), ip, for 14 weeks).
      Cardiac contractile function was evaluated in vivo. The morphological features of
      cardiac fibrosis were observed using immunohistochemistry and TEM. The mRNA
      expression of JNK, TGFbeta1, type-I, and type-III procollagen was assessed with
      RT-PCR. The phosphorylation of MYPT1, JNK and Smad2/3, as well as the protein
      levels of TGFbeta1 and c-Jun, were evaluated using Western blotting. RESULTS: In
      untreated diabetic rats, myocardial fibrosis was developed and the heart
      contractility was significantly reduced as compared to the control rats. In the
      hearts of untreated diabetic rats, the mRNA expression level and activity of JNK
      were upregulated; the expression of TGFbeta1 and phosphorylation of Smad2/3 were
      increased. In the hearts of treated diabetic rat, activation of JNK and
      TGFbeta/Smad was significantly decreased, myocardial fibrosis was reduced, and
      cardiac contractile function improved. CONCLUSION: The data suggest that fasudil
      hydrochloride hydrate ameliorates myocardial fibrosis in rats with type 2
      diabetes at least in part through inhibiting the JNK and TGFbeta/Smad pathways.
      Inhibition of RhoA/ROCK may be a novel therapeutic target for prevention of
      diabetic cardiomyopathy.

PMID- 21743487
TI  - The proto-oncogene Pim-1 is a target of miR-33a.
AB  - The constitutively active serine/threonine kinase Pim-1 is upregulated in
      different cancer types, mainly based on the action of several interleukines and
      growth factors at the transcriptional level. So far, a regulation of oncogenic
      Pim-1 by microRNAs (miRNAs) has not been reported. Here, we newly establish miR
      33a as a miRNA with potential tumor suppressor activity, acting through
      inhibition of Pim-1. A screen for miRNA expression in K562 lymphoma, LS174T colon
      carcinoma and several other cell lines revealed generally low endogenous miR-33a
      levels relative to other miRNAs. Transfection of K562 and LS174T cells with a miR
      33a mimic reduced Pim-1 levels substantially. In contrast, the cell-cycle
      regulator cyclin-dependent kinase 6 predicted to be a conserved miR-33a target,
      was not downregulated by the miR-33a mimic. Seed mutagenesis of the Pim-1 3'
      untranslated region in a luciferase reporter construct and in a Pim-1 cDNA
      expressed in Pim-1-deficient Skov-3 cells demonstrated specific and direct
      downregulation of Pim-1 by the miR-33a mimic. The persistence of this effect was
      comparable to that of a small interfering RNA-mediated knockdown of Pim-1,
      resulting in decelerated cell proliferation. In conclusion, we demonstrate the
      potential of miR-33a to act as a tumor suppressor miRNA, which suggests miR-33a
      replacement therapy through delivery of miR mimics as a novel therapeutic
      strategy.

PMID- 21743488
TI  - Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal
      filling.
AB  - A large fraction of ductal carcinoma in situ (DCIS), a non-invasive precursor
      lesion of invasive breast cancer, overexpresses the HER2/neu oncogene. The ducts
      of DCIS are abnormally filled with cells that evade apoptosis, but the underlying
      mechanisms remain incompletely understood. We overexpressed HER2 in mammary
      epithelial cells and observed growth factor-independent proliferation. When grown
      in extracellular matrix as three-dimensional spheroids, control cells developed a
      hollow lumen, but HER2-overexpressing cells populated the lumen by evading
      apoptosis. We demonstrate that HER2 overexpression in this cellular model of DCIS
      drives transcriptional upregulation of multiple components of the Notch survival
      pathway. Importantly, luminal filling required upregulation of a signaling
      pathway comprising Notch3, its cleaved intracellular domain and the
      transcriptional regulator HES1, resulting in elevated levels of c-MYC and cyclin
      D1. In line with HER2-Notch3 collaboration, drugs intercepting either arm
      reverted the DCIS-like phenotype. In addition, we report upregulation of Notch3
      in hyperplastic lesions of HER2 transgenic animals, as well as an association
      between HER2 levels and expression levels of components of the Notch pathway in
      tumor specimens of breast cancer patients. Therefore, it is conceivable that the
      integration of the Notch and HER2 signaling pathways contributes to the
      pathophysiology of DCIS.

PMID- 21743489
TI  - NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the
      HMGB1-mediated autophagic response.
AB  - Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene
      family, is known to have important roles in proliferation and growth of tumor
      cells and in chemotherapy resistance. Yet, the mechanisms underlying how NAC1
      contributes to drug resistance remain largely unclear. We report here that
      autophagy was involved in NAC1-mediated resistance to cisplatin, a commonly used
      chemotherapeutic drug in the treatment of ovarian cancer. We found that treatment
      with cisplatin caused an activation of autophagy in ovarian cancer cell lines,
      A2780, OVCAR3 and SKOV3. We further demonstrated that knockdown of NAC1 by RNA
      interference or inactivation of NAC1 by inducing the expression of a NAC1
      deletion mutant that contains only the BTB/POZ domain significantly inhibited the
      cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity.
      Moreover, inhibition of autophagy and sensitization to cisplatin by NAC1
      knockdown or inactivation were accompanied by induction of apoptosis. To confirm
      that the sensitizing effect of NAC1 inhibition on the cytotoxicity of cisplatin
      was attributed to suppression of autophagy, we assessed the effects of the
      autophagy inhibitors 3-methyladenosine and chloroquine, and small interfering
      RNAs (siRNAs) targeting beclin 1 or Atg5 on the cytotoxicity of cisplatin.
      Treatment with 3-methyladenosine, chloroquine or beclin 1 and Atg5-targeted siRNA
      also enhanced the sensitivity of SKOV3, A2780 and OVCAR3 cells to cisplatin,
      indicating that suppression of autophagy indeed renders tumor cells more
      sensitive to cisplatin. Regulation of autophagy by NAC1 was mediated by the high
      mobility group box 1 (HMGB1), as the functional status of NAC1 was associated
      with the expression, translocation and release of HMGB1. The results of our study
      not only revealed a new mechanism determining cisplatin sensitivity but also
      identified NAC1 as a novel regulator of autophagy. Thus, the NAC1-mediated
      autophagy may be exploited as a new target for enhancing the efficacy of
      cisplatin against ovarian cancer and other types of malignancies.

PMID- 21743490
TI  - Telomerase promotes efficient cell cycle kinetics and confers growth advantage to
      telomerase-negative transformed human cells.
AB  - Constitutive telomerase activity maintains telomere length and confers immortal
      phenotypes to human cancers. The prevalence of telomerase, rather than a
      homologous recombination-based mechanism, in telomere length maintenance suggests
      that telomerase also has auxiliary roles in tumorigenesis. Here, we investigate
      growth advantages provided by the telomerase enzyme in oncogene-transformed human
      cells that do not require telomerase activity for telomere length control. Our
      data suggest that in oncogene-transformed cells, telomerase activity accelerates
      cell growth kinetics in a cell cycle phase-specific manner and promotes anchorage
      independent growth. Coculture experiments demonstrated that this growth advantage
      conferred by telomerase activity is not due to increased cellular cross-talk.
      Growth advantages provided by telomerase required all functional aspects of the
      enzyme. Dissociation-of-activity-in-telomerase mutants and other functionally
      defective versions of telomerase were unable to promote oncogene-transformed cell
      growth, suggesting that canonical telomerase activities may be involved. We
      conclude that telomerase provides advantages to oncogene-transformed human cells,
      thereby supporting the development of telomerase-based anticancer chemotherapies
      targeting these growth-promoting effects.

PMID- 21743491
TI  - Microsomal prostaglandin E synthase-1 promotes hepatocarcinogenesis through
      activation of a novel EGR1/beta-catenin signaling axis.
AB  - Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that couples with
      cyclooxygenase-2 (COX-2) for the production of PGE(2). Although COX-2 is known to
      mediate the growth and progression of several human cancers including
      hepatocellular carcinoma (HCC), the role of mPGES-1 in hepatocarcinogenesis is
      not well established. This study provides novel evidence for a key role of mPGES
      1 in HCC growth and progression. Forced overexpression of mPGES-1 in two HCC cell
      lines (Hep3B and Huh7) increased tumor cell growth, clonogenic formation,
      migration and invasion, whereas knockdown of mPGES-1 inhibited these parameters,
      in vitro. In a mouse tumor xenograft model, mPGES-1-overexpressed cells formed
      palpable tumors at earlier time points and developed larger tumors when compared
      with the control (P<0.01); in contrast, mPGES-1 knockdown delayed tumor
      development and reduced tumor size (P<0.01). Mechanistically, mPGES-1-induced HCC
      cell proliferation, invasion and migration involve PGE(2) production and
      activation of early growth response 1 (EGR1) and beta-catenin. Specifically,
      mPGES-1-derived PGE(2) induces the formation of EGR1-beta-catenin complex, which
      interacts with T-cell factor 4/lymphoid enhancer factor 1 transcription factors
      and activates the expression of beta-catenin downstream genes. Our findings
      depict a novel crosstalk between mPGES-1/PGE(2) and EGR1/beta-catenin signaling
      that is critical for hepatocarcinogenesis.

PMID- 21743492
TI  - miR-221/222 overexpession in human glioblastoma increases invasiveness by
      targeting the protein phosphate PTPMU.
AB  - Glioblastoma is the most frequent brain tumor in adults and is the most lethal
      form of human cancer. Despite the improvements in treatments, survival of
      patients remains poor. In order to identify microRNAs (miRs) involved in glioma
      tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in
      the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non
      tumorigenic T98G cells. Among different miRs we focused our attention on miR-221
      and -222. We demonstrated the presence of a binding site for these two miRs in
      the 3' untranslated region of the protein tyrosine phosphatase MU (PTPMU).
      Previous studies indicated that PTPMU suppresses cell migration and is
      downregulated in glioblastoma. Significantly, we found that miR-221 and -222
      overexpression induced a downregulation of PTPMU as analyzed by both western blot
      and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell
      migration and growth in soft agar in glioma cells. Interestingly, the re
      expression of PTPMU gene was able to revert the miR-222 and -221 effects on cell
      migration. Furthermore, we found an inverse correlation between miR-221 and -222
      and PTPMU in human glioma cancer samples. In conclusion, our results suggest that
      miR-221 and -222 regulate glioma tumorigenesis at least in part through the
      control of PTPMU protein expression.

PMID- 21743493
TI  - FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells.
AB  - The transcription factor FOXP3 has been identified as a tumour suppressor in the
      breast and prostate epithelia, but little is known about its specific mechanism
      of action. We have identified a feed-forward regulatory loop in which FOXP3
      suppresses the expression of the oncogene SATB1. In particular, we demonstrate
      that SATB1 is not only a direct target of FOXP3 repression, but that FOXP3 also
      induces two miRs, miR-7 and miR-155, which specifically target the 3'-UTR of
      SATB1 to further regulate its expression. We conclude that FOXP3-regulated miRs
      form part of the mechanism by which FOXP3 prevents the transformation of the
      healthy breast epithelium to a cancerous phenotype. Approaches aimed at restoring
      FOXP3 function and the miRs it regulates could help provide new approaches to
      target breast cancer.

PMID- 21743494
TI  - E2F1-dependent oncogenic addiction of melanoma cells to MDM2.
AB  - One of the defining features of aggressive melanomas is their complexity.
      Hundreds of mutations and an ever increasing list of changes in the transcriptome
      and proteome distinguish normal from malignant melanocytic cells. Yet, despite
      this altered genetic background, a long-known attribute of melanomas is a
      relatively low rate of mutations in the p53 gene. However, it is unclear whether
      p53 is maintained in melanoma cells because it is required for their survival, or
      because it is functionally disabled. More pressing from a translational
      perspective, is to define whether there is a tumor cell-selective wiring of p53
      that offers a window for therapeutic intervention. Here, we provide genetic and
      pharmacological evidence demonstrating that p53 represents a liability to
      melanoma cells, which they thwart by assuming an oncogenic dependency on the E3
      ligase murine double minute-2 (MDM2). Specifically, we used a combination of RNA
      interference and two structurally independent small molecule inhibitors of the
      p53-MDM2 interaction to assess the relative requirement of both proteins for the
      viability of normal melanocytes and a broad panel of melanoma cell lines. We
      demonstrated in vitro and in vivo that MDM2 is selectively required to blunt
      latent pro-senescence signals in melanoma cells. Notably, the outcome of MDM2
      inactivation depends not only on the mutational status of p53, but also on its
      ability to signal to the transcription factor E2F1. These data support MDM2 as a
      drug target in melanoma cells, and identify E2F1 as a biomarker to consider when
      stratifying putative candidates for clinical studies of p53-MDM2 inhibitors.

PMID- 21743495
TI  - Overexpression of 14-3-3zeta in cancer cells activates PI3K via binding the p85
      regulatory subunit.
AB  - The ubiquitously expressed 14-3-3 proteins regulate many pathways involved in
      transformation. Previously, we found that 14-3-3zeta overexpression increased Akt
      phosphorylation in human mammary epithelial cells. Here, we investigated the
      clinical relevance and molecular mechanism of 14-3-3zeta-overexpression-mediated
      Akt phosphorylation, and its potential impact on breast cancer progression. We
      found that 14-3-3zeta overexpression was significantly (P=0.005) associated with
      increased Akt phosphorylation in human breast tumors. Additionally, 14-3-3zeta
      overexpression combined with strong Akt phosphorylation was significantly
      (P=0.01) associated with increased cancer recurrence in patients. In contrast,
      knockdown of 14-3-3zeta expression by small interfering RNA in cancer cell lines
      and tumor xenografts reduced Akt phosphorylation. Furthermore, 14-3-3zeta
      enhanced Akt phosphorylation through activation of phosphoinositide 3-kinase
      (PI3K). Mechanistically, 14-3-3zeta bound to the p85 regulatory subunit of PI3K
      and increased PI3K translocation to the cell membrane. A single 14-3-3-binding
      motif encompassing serine 83 on p85 is largely responsible for 14-3-3zeta
      mediated p85 binding and PI3K/Akt activation. Mutation of serine 83 to alanine on
      p85 inhibited 14-3-3zeta binding to the p85 subunit of PI3K, reduced PI3K
      membrane localization and activation, impeded anchorage-independent growth and
      enhanced stress-induced apoptosis. These findings revealed a novel mechanism by
      which 14-3-3zeta overexpression activates PI3K, a key node in the mitogenic
      signaling network known to promote malignancies in many cell types.

PMID- 21743496
TI  - Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene,
      Fibulin-2, in nasopharyngeal carcinoma.
AB  - Fibulin-2 (FBLN2) has been identified as a candidate tumor-suppressor gene in
      nasopharyngeal carcinoma (NPC). Originally identified through a chromosome 3 NotI
      genomic microarray screen, it shows frequent deletion or methylation in NPC.
      FBLN2 is located on chromosome 3p25.1 and is associated with tumor development
      through its important interactions with the extracellular matrix (ECM) proteins.
      FBLN2 encodes two isoforms. The short isoform (FBLN2S) is expressed abundantly in
      normal tissues, but is dramatically downregulated in NPC, while the long isoform
      (FBLN2L) is either not detectable or is expressed only at low levels in both
      normal and tumor tissues. Reintroduction of this FBLN2S inhibited cell
      proliferation, migration, invasion and angiogenesis in vitro. Furthermore, in
      vivo studies in nude mice show its expression is associated with tumor and
      angiogenesis suppression. FBLN2-associated angiogenesis occurs via concomitant
      downregulation of vascular endothelial growth factor and matrix metalloproteinase
      2. This study provides compelling evidence that FBLN2S has an important tumor
      suppressive and anti-angiogenic role in NPC.

PMID- 21743497
TI  - Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90
      phenotype.
AB  - Identification and characterization of cancer stem cells (CSCs) in gastric cancer
      are difficult owing to the lack of specific markers and consensus methods. In
      this study, we show that cells with the CD90 surface marker in gastric tumors
      could be enriched under non-adherent, serum-free and sphere-forming conditions.
      These CD90(+) cells possess a higher ability to initiate tumor in vivo and could
      re-establish the cellular hierarchy of tumors from single-cell implantation,
      demonstrating their self-renewal properties. Interestingly, higher proportion of
      CD90(+) cells correlates with higher in vivo tumorigenicity of gastric primary
      tumor models. In addition, it was found that ERBB2 was overexpressed in about 25%
      of the gastric primary tumor models, which correlates with the higher level of
      CD90 expression in these tumors. Trastuzumab (humanized anti-ERBB2 antibody)
      treatment of high-tumorigenic gastric primary tumor models could reduce the
      CD90(+) population in tumor mass and suppress tumor growth when combined with
      traditional chemotherapy. Moreover, tumorigenicity of tumor cells could also be
      suppressed when trastuzumab treatment starts at the same time as cell
      implantation. Therefore, we have identified a CSC population in gastric primary
      tumors characterized by their CD90 phenotype. The finding that trastuzumab
      targets the CSC population in gastric tumors suggests that ERBB2 signaling has a
      role in maintaining CSC populations, thus contributing to carcinogenesis and
      tumor invasion. In conclusion, the results from this study provide new insights
      into the gastric tumorigenic process and offer potential implications for the
      development of anticancer drugs as well as therapeutic treatment of gastric
      cancers.

PMID- 21743498
TI  - The effect Akt2 deletion on tumor development in Pten(+/-) mice.
AB  - The serine/threonine kinase Akt is frequently activated in human cancers and is
      considered an attractive therapeutic target. However, the relative contributions
      of the different Akt isoforms to tumorigenesis, and the effect of their
      deficiencies on cancer development are not well understood. We had previously
      shown that Akt1 deficiency is sufficient to markedly reduce the incidence of
      tumors in Pten(+/-) mice. Particularly, Akt1 deficiency inhibits endometrial
      carcinoma and prostate neoplasia in Pten(+/-) mice. Here, we analyzed the effect
      of Akt2 deficiency on the incidence of tumors in Pten(+/-) mice. Relative to
      Akt1, Akt2 deficiency had little-to-no effect on the incidence of prostate
      neoplasia, endometrial carcinoma, intestinal polyps and adrenal lesions in
      Pten(+/-) mice. However, Akt2 deficiency significantly decreased the incidence of
      thyroid tumors in Pten(+/-), which correlates with the relatively high level of
      Akt2 expression in the thyroid. Thus, unlike Akt1 deletion, Akt2 deletion is not
      sufficient to markedly inhibit tumorigenesis in Pten(+/-) mice in most tested
      tissues. The relatively small effect of Akt2 deletion on the inhibition of
      tumorigenesis in Pten(+/-) mice could be explained, in part, by an insufficient
      decrease in total Akt activity, due to the relatively lower Akt2 versus Akt1
      expression, and relatively high blood insulin levels in Pten(+/-)Akt2(-/-) mice.
      The relatively high blood insulin levels in Pten(+/-)Akt2(-/-) mice may elevate
      the activity of Akt1, and possibly Akt3, thus, limiting the reduction of total
      Akt activity and preventing this activity from dropping to a threshold level
      required to inhibit tumorigenesis.

PMID- 21743499
TI  - Current status of allogeneic HST for chronic myelomonocytic leukemia.
AB  - Allogeneic hematopoietic SCT (HST) offers the only curative potential for
      patients with chronic myelomonocytic leukemia (CMML). However, there is a paucity
      of data addressing this approach in CMML. The disease is a relatively under
      represented myelodysplastic (MDS)/myeloproliferative subtype among transplant
      eligible patients. Non-randomized studies suggest that long-term remissions are
      achievable when using myeloablative or reduced intensity conditioning
      transplantation. Allogeneic SCT for CMML is often reported as part of MDS
      registry data. The largest series in adult patients reported a disappointing long
      term relapse-free survival (RFS) of 18%. The Fred Hutchinson Cancer and Research
      Center group reported a 40% long-term RFS for a mixed group of adults and
      children with CMML who were transplanted over two decades. In this study, we
      performed a literature search and reviewed available data for adult CMML patients
      undergoing HST. The dearth of data that span two decades with changing transplant
      practices prohibited us from performing a formal meta-analysis. However, we
      elected to present the current status of HST in adult CMML patients. Carefully
      selected CMML patients may have the most benefit from this curative approach.

PMID- 21743500
TI  - Serial intestinal endoscopic examinations of patients with persistent diarrhea
      after allo-SCT.
AB  - Gastrointestinal (GI) GVHD after allo-SCT is diagnosed on the basis of symptoms
      and findings in endoscopic mucosal biopsy specimens. However, GI symptoms often
      persist despite treatment and whether a second endoscopy may be helpful in
      determining the most suitable therapy is not established. We identified 31
      patients with persistent diarrhea who underwent more than one endoscopic study.
      All cases underwent serial microbiological stool analysis and CMV-detecting
      assays on serum and biopsies. Of the 31 initial GI biopsies, 20 (64.5%) were
      classified as GVHD, two (6.5%) as GVHD with CMV, four (13%) as non-CMV infection,
      and five (16%) as normal or unspecific. The second GI biopsies were diagnostic of
      GVHD in nine cases (29%), GVHD simultaneously with CMV infection in four (13%),
      regenerative changes post-GVHD in five (16%), CMV infection in four (13%), and
      normal or unspecific in nine (29%). In 22 of the 31 patients (71%), the
      histological findings of the second/third endoscopic biopsies differed from the
      findings of the first endoscopy and led to a therapy change in 77%. In
      conclusion, serial GI endoscopies are of reliable diagnostic value and can impact
      on therapeutic decision-making for patients with persistent diarrhea after allo
      SCT.

PMID- 21743501
TI  - Uptake and outcome of assisted reproductive techniques in long-term survivors of
      SCT.
AB  - We have audited the invitation for uptake and outcome of artificial reproductive
      techniques in patients undergoing SCT for haematological malignancy, with the aim
      of improving our pre-transplant counselling. A postal survey was sent to 434
      patients in our centre surviving a minimum of 2 years after allo-SCT, of whom 221
      patients responded. Of 112 male patients, 79 were offered sperm storage, 42
      banked sperm and 25 subsequently attempted parenthood with stored sperm. A total
      of 18 were successful, with 29 children born a median of 8 years (range 1-22
      years) following SCT. Of 72 females <42 years old, 33 were offered storage of
      embryos/eggs/ovarian tissue and 12 accepted. Following SCT, four women attempted
      pregnancy using cryopreserved embryos, with two successes. The majority of
      patients who were not counselled about infertility or not offered fertility
      preservation options provided a likely reason, with completion of family being
      the most frequent. Nonetheless, 16 patients (11/72 women and 5/112 men) could not
      provide a reason for the lack of information/invitation. In conclusion, uptake of
      gamete/embryo storage is high when offered and collected material is used
      frequently. Pregnancies in partners of male patients were usually successful and
      our data highlight the value of prolonged cryostorage.

PMID- 21743502
TI  - Role of HCT-comorbidity index, age and disease status at transplantation in
      predicting survival and non-relapse mortality in patients with myelodysplasia and
      leukemia undergoing reduced-intensity-conditioning hemopoeitic progenitor cell
      transplantation.
AB  - Reduced-intensity-conditioning (RIC) regimens have allowed older patients to have
      allogeneic hemopoietic progenitor cell transplantation (HCT). This retrospective
      study was done to assess the impact of the HCT-comorbidity index (HCT-CI) in
      addition to other pre-transplant factors on the outcome of RIC transplants. In
      all 121 such patients were transplanted between 2002 and 2008 at two centers
      using fludarabine, melphalan and alumtuzumab conditioning. The OS and non-relapse
      mortality (NRM) were 56% and 30% at 2 years, respectively. The NRM of patients
      with HCT-CI >= 3 was not significantly different from the NRM of those with HCT
      CI 0-2 (P value 0.24). Age and disease status at transplantation were significant
      factors affecting OS (P value 0.07 and 0.008, respectively), with no impact on
      NRM (P value 0.14 and 0.24, respectively). Although HCT-CI on its own did not
      independently predict NRM or survival, taken together with age and disease status
      at transplantation, it can be utilized to further delineate RIC allograft
      recipients into groups with different outcomes. Patients with none or one of
      these three adverse factors (age >= 60 years, leukemia in second CR or PR/high
      risk myelodysplasia (MDS) and HCT-CI >= 3) had a 2-year NRM and survival of 18%
      and 80%, respectively, which was significantly better than those of patients with
      two or more of these adverse factors with 2-year NRM and survival of 46% (P value
      0.03) and 40% (P value 0.02), respectively. None of the patients with all three
      adverse factors (age >= 60 years, leukemia in second CR or PR/high-risk MDS and
      HCT-CI >= 3) had survived for 2 years (median survival 12 months). This
      information can be used to guide patient selection for RIC transplants and to
      appropriately counsel patients of the risks and benefits of this treatment.

PMID- 21743503
TI  - Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD
      1: clinical efficacy and importance of chimerism.
AB  - Pediatric patients with leukocyte adhesion deficiency type-I (LAD-I) experience
      severe and recurrent life-threatening bacterial infections with failure of pus
      formation and delayed wound healing. LAD-I is a rare inherited disease caused by
      mutation in the leukocyte CD18 integrin expression, resulting in defective
      adherence and migration of leukocytes, in particular neutrophilic granulocytes
      through the intravascular space. Hematopoietic SCT is the only curative treatment
      option available to patients with LAD-I. Since 2007, in a prospective trial,
      reduced-intensity conditioning regimen have been developed for 10 consecutive
      patients with LAD-I who were referred to our center. Based upon available data,
      it is the first time that such a number of patients affected by LAD-I have been
      treated with this regimen. This study attempts to show that reduced-intensity
      regimen leads to a favorable result in LAD-I patients even in those who have
      experienced comorbid complications. Following transplantation, some patients
      develop mixed chimerism, however, in our study mixed chimerism was not followed
      by transplant rejection.

PMID- 21743504
TI  - Automated localization of retinal features.
AB  - Retinal fundus images are widely used in the diagnosis and treatment of various
      eye diseases, such as diabetic retinopathy and glaucoma. A computer-aided retinal
      fundus image analysis could provide an immediate detection and characterization
      of retinal features prior to specialist inspection. This paper proposes an
      approach to automatically localize the main features in fundus images, such as
      blood vessels, optic disc, and fovea by exploiting the spatial and geometric
      relations that govern their distribution within the fundus image. The blood
      vessels are segmented by scale-space analysis. The average thickness of these
      blood vessels is then computed using the vessels centerlines and orientations
      from a Hessian matrix. The optic disc is localized using the circular Hough
      transform, the parabolic Hough transform fitting, and the localization of the
      fovea. The proposed method can be extended to establish a foveal coordinate
      system to facilitate grading lesions based on the spatial relationships between
      lesions and landmark features. The proposed method was evaluated on publicly
      available image databases, and the results have demonstrated a significant
      improvement over the current state-of-the-art methods.

PMID- 21743505
TI  - Absolute refractometry of dry gas to +/-3 parts in 109.
AB  - We present a method of measuring the refractive index of dry gases absolutely at
      632.8 nm wavelength using a Fabry-Perot cavity with an expanded uncertainty of
      <3*10-9 (coverage factor k=2). The main contribution to this uncertainty is how
      well vacuum-to-atmosphere compression effects (physical length variation) in the
      cavities can be corrected. This paper describes the technique and reports
      reference values for the refractive indices of nitrogen and argon gases at 100
      kPa and 20  degrees C with an expanded uncertainty of <9*10-9 (coverage factor
      k=2), with the additional and larger part of this uncertainty coming from the
      pressure and temperature measurement.

PMID- 21743506
TI  - Highly sensitive fiber loop ringdown strain sensor using photonic crystal fiber
      interferometer.
AB  - A highly sensitive strain sensor is demonstrated by introducing a photonic
      crystal fiber (PCF) Mach-Zehnder interferometer (MZI) in a cavity ringdown fiber
      loop as a sensing element. The MZI is fabricated by splicing a short length of
      PCF between two single-mode fibers with collapsed air holes over a short region
      at two splicing points, which allows coupling between core and cladding modes
      inside the PCF. By measuring the decay constants of the fiber ringdown loop under
      different applied strains, a high strain sensitivity of ~0.21 MUs-1/epsilonm and
      a minimum detectable strain of ~3.6 MUepsilon are obtained. As a benefit from the
      ultralow thermal dependence of PCF, the maximum temperature-induced measurement
      error could be reduced to ~0.24 MUepsilon.

PMID- 21743507
TI  - Selection of dark modes in resonators with conical reflectors.
AB  - Selection of modes containing different dark regions was studied in resonators
      with conical reflectors. The possibility of selecting whole subgroups of such
      modes was shown in circularly symmetric resonators. To handle single-mode
      selection employing extra intracavity spatial filters, modified integral
      equations and a numerical method of their analysis are proposed. Usage of the
      filter symmetry reduces the size of the four-dimensional matrices corresponding
      to the equation kernels, and they are analyzed by algorithms for two-dimensional
      matrices with the best convergence. The optimum resonator parameters for
      effective selection of different dark modes are found.

PMID- 21743508
TI  - Improving fast aspheric convex surface tests with dynamic null screens using
      LCDs.
AB  - A method for testing fast aspheric convex surfaces with dynamic null screens
      using LCDs is shown. A flat null screen is designed and displayed on an LCD
      monitor with drop-shaped spots in such a way that the image, which is formed by
      reflection on the test surface, becomes an exactly square array of circular spots
      if the surface is perfect. Any departure from this geometry is indicative of
      defects on the surface. Here the whole surface is tested at once. The position of
      the spots on the LCD can be changed in a dynamic way, to perform point-shifting
      of the image spots. The proposed procedure improves the dynamic point-shifting
      method. As has been shown previously, this process reduces the numerical error
      during the integration procedure, thereby improving the sensitivity of the test.
      The positioning accuracy for the screen spots is related to the LCD's spatial
      resolution. Results of the evaluation of a parabolic convex surface with f/#=0.22
      are shown.

PMID- 21743509
TI  - Application of the radial basis function interpolation to phase extraction from a
      single electronic speckle pattern interferometric fringe.
AB  - In this paper, we introduce the radial basis function (RBF) interpolation method
      to electronic speckle pattern interferometry (ESPI) and propose the RBF
      interpolation method to obtain unwrapped phase values based on a skeleton map.
      Because of the excellent approximation properties of the RBF interpolation, the
      proposed method can extract accurate phase values from a single fringe pattern
      effectively, even using a simple 3*3 mean filter as preprocessing. Using our
      method, both special filtering methods for ESPI fringes as preprocessing and
      postprocessing, including a dilatation and erosion algorithm for pruning and
      connecting and the smooth algorithm for improving the phase values are not
      needed. We test our method on a computer-simulated and two experimentally
      obtained poor-quality fringe patterns. The results have demonstrated that our RBF
      interpolation method works well even under a seriously disconnected skeleton map
      where it is impossible to apply the widely used, Matlab function grid data
      interpolation or the backpropagation neural networks method [Appl. Opt. 46, 7475
      (2007)].

PMID- 21743510
TI  - Large-mode-area leaky optical fiber fabricated by MCVD.
AB  - A large-mode-area single-mode optical fiber based on leaky-mode filtering was
      prepared by a modified chemical vapor deposition (MCVD) technique. The fiber has
      a leaky cladding that discriminates the fundamental mode from higher-order modes.
      A preliminary version has a 25 MUm core diameter and 0.11 numerical aperture. A
      Gaussian-like mode with 22 MUm mode field diameter was observed after 3 m
      propagation, in agreement with modeling.

PMID- 21743511
TI  - All-fiber magneto-optic Sagnac interferometer.
AB  - An all-fiber magneto-optic Sagnac interferometer (AFMOSI) utilizing intrinsic
      Faraday effects in highly nonlinear fibers (HNLFs) is presented for the first
      time (to our knowledge). The performance of the AFMOSI was investigated
      theoretically by use of the transfer matrix approach. The theoretical results
      were verified by the experiment employing an all-fiber magnetic-optic cell that
      consists of a 30 m long HNLF and a 92 mm diameter toroid coil. Our experiments
      show that, when the linear birefringence of the AFMOSI is adjusted to 0, the
      change of the transmission can be over 10 dB as the magnetic induction B
      increases from 0 to 180 Gs. The sensitivity of the AFMOSI is determined by the
      coupling ratio of the fiber coupler, the loss of the loop, and the length of the
      HNLF. Most importantly, the linear birefringence of the AFMOSI can be obtained by
      evaluating its performance of magnetic field response. This is very useful for
      studying the influence of the linear birefringence on the performance of a
      nonlinear optical loop mirror that is controlled by the Faraday effect.

PMID- 21743512
TI  - Generalized Bessel beams in modified axially symmetric graded index structures.
AB  - We explore a general type of stable Bessel beams in graded index media. The
      proposed axially symmetric medium is characterized by an "alpha" index profile.
      Explicit solutions for the radial envelope of the field E(r) are derived in terms
      of generalized Bessel functions. Emphasis is given on illustrating how far the
      conditions of the proposed modified structure permit only a Bessel function of
      the first kind to be uniquely retained in the solution. This paper considers both
      the optical and mathematical aspects. Some numerical examples corroborating our
      theoretical results are included, showing the stability, propagation, and
      diffraction of such Bessel beams.

PMID- 21743513
TI  - Optical distortion evaluation of an aerodynamically heated window using the
      interfacial fluid thickness concept.
AB  - The interfacial fluid thickness (IFT) concept was used to develop a harmonic-mean
      refractive index gradient magnitude threshold to retrieve the high refractive
      index gradient regions of an aerodynamically heated window. The retrieved high
      gradient regions were used to reconstruct the refractive index field of the
      window. The numerical three-dimensional optical distortion evaluation was
      conducted for both the reconstructed and the original refractive index fields of
      the window using the ray-tracing program based on a recursive algorithm. Wave
      aberration results show that the methodology based on the IFT concept reduces the
      refractive index information required to capture the essential optical distortion
      of the window. The method can also be used for numerically evaluating the optical
      distortion of the window.

PMID- 21743514
TI  - Estimating optical absorption, scattering, and Grueneisen distributions with
      multiple-illumination photoacoustic tomography.
AB  - While photoacoustic methods offer significant promise for high-resolution optical
      contrast imaging, quantification has thus far proved challenging. In this paper,
      a noniterative reconstruction technique for producing quantitative photoacoustic
      images of both absorption and scattering perturbations is introduced for the case
      when the optical properties of the turbid background are known and multiple
      optical illumination locations are used. Through theoretical developments and
      computational examples, it is demonstrated that multiple-illumination
      photoacoustic tomography (MI-PAT) can alleviate ill-posedness due to absorption
      scattering nonuniqueness and produce quantitative high-resolution reconstructions
      of optical absorption, scattering, and Gruneisen parameter distributions. While
      numerical challenges still exist, we show that the linearized MI-PAT framework
      that we propose has orders of magnitude improved condition number compared with
      CW diffuse optical tomography.

PMID- 21743515
TI  - An inherent-optical-property-centered approach to correct the angular effects in
      water-leaving radiance.
AB  - Remote-sensing reflectance (R(rs)), which is defined as the ratio of water
      leaving radiance (L(w)) to downwelling irradiance just above the surface
      (E(d)(0+)), varies with both water constituents (including bottom properties of
      optically-shallow waters) and angular geometry. L(w) is commonly measured in the
      field or by satellite sensors at convenient angles, while E(d)(0+) can be
      measured in the field or estimated based on atmospheric properties. To isolate
      the variations of R(rs) (or L(w)) resulting from a change of water constituents,
      the angular effects of R(rs) (or L(w)) need to be removed. This is also a
      necessity for the calibration and validation of satellite ocean color
      measurements. To reach this objective, for optically-deep waters where bottom
      contribution is negligible, we present a system centered on water's inherent
      optical properties (IOPs). It can be used to derive IOPs from angular
      R<sub>rs</sub> and offers an alternative to the system centered on the
      concentration of chlorophyll. This system is applicable to oceanic and coastal
      waters as well as to multiband and hyperspectral sensors. This IOP-centered
      system is applied to both numerically simulated data and in situ measurements to
      test and evaluate its performance. The good results obtained suggest that the
      system can be applied to angular R(rs) to retrieve IOPs and to remove the angular
      variation of R(rs).

PMID- 21743516
TI  - Neural network approach to retrieve the inherent optical properties of the ocean
      from observations of MODIS.
AB  - Retrieving the inherent optical properties of water from remote sensing
      multispectral reflectance measurements is difficult due to both the complex
      nature of the forward modeling and the inherent nonlinearity of the inverse
      problem. In such cases, neural network (NN) techniques have a long history in
      inverting complex nonlinear systems. The process we adopt utilizes two NNs in
      parallel. The first NN is used to relate the remote sensing reflectance at
      available MODIS-visible wavelengths (except the 678 nm fluorescence channel) to
      the absorption and backscatter coefficients at 442 nm (peak of chlorophyll
      absorption). The second NN separates algal and nonalgal absorption components,
      outputting the ratio of algal-to-nonalgal absorption. The resulting synthetically
      trained algorithm is tested using both the NASA Bio-Optical Marine Algorithm Data
      Set (NOMAD), as well as our own field datasets from the Chesapeake Bay and Long
      Island Sound, New York. Very good agreement is obtained, with R2 values of
      93.75%, 90.67%, and 86.43% for the total, algal, and nonalgal absorption,
      respectively, for the NOMAD. For our field data, which cover absorbing waters up
      to about 6 m-1, R2 is 91.87% for the total measured absorption.

PMID- 21743517
TI  - Design of a high-efficiency seven-port beam splitter using a dual duty cycle
      grating structure.
AB  - In this paper, we propose a compact seven-port beam splitter which is constructed
      using only a single-layer high-density grating with a dual duty cycle structure.
      The properties of this grating are investigated by a simplified modal method. The
      diffraction efficiency can be achieved around 10% more than conventional Dammann
      gratings while the uniformity can still be maintained at less than 1%. The effect
      of deviations from the design parameters on the performance of the grating is
      also presented.

PMID- 21743518
TI  - Iris segmentation using an edge detector based on fuzzy sets theory and cellular
      learning automata.
AB  - Iris-based biometric systems identify individuals based on the characteristics of
      their iris, since they are proven to remain unique for a long time. An iris
      recognition system includes four phases, the most important of which is
      preprocessing in which the iris segmentation is performed. The accuracy of an
      iris biometric system critically depends on the segmentation system. In this
      paper, an iris segmentation system using edge detection techniques and Hough
      transforms is presented. The newly proposed edge detection system enhances the
      performance of the segmentation in a way that it performs much more efficiently
      than the other conventional iris segmentation methods.

PMID- 21743519
TI  - Terahertz reflectivities of metal-coated mirrors.
AB  - Terahertz (THz) reflectivities of a variety of metal-coated mirrors were
      measured. Gold, silver, and aluminum coatings were tested and compared. It was
      found that all types of optical metal-coated mirrors perform equally well as THz
      reflectors.

PMID- 21743520
TI  - On the importance of path for phase unwrapping in synthetic aperture radar
      interferometry.
AB  - Phase unwrapping is a key procedure in interferometric synthetic aperture radar
      studies, translating ambiguous phase observations to topography, and surface
      deformation estimates. Some unwrapping algorithms are conducted along specific
      paths based on different selection criteria. In this study, we analyze six
      unwrapping paths: line scan, maximum coherence, phase derivative variance, phase
      derivative variance with branch-cut, second-derivative reliability, and the
      Fisher distance. The latter is a new path algorithm based on Fisher information
      theory, which combines the phase derivative with the expected variance to get a
      more robust path, potentially performing better than others in the case of low
      image quality. In order to compare only the performance of the paths, the same
      unwrapping function (phase derivative integral) is used. Results indicate that
      the Fisher distance algorithm gives better results in most cases.

PMID- 21743521
TI  - Hybrid optical (freeform) components--functionalization of nonplanar optical
      surfaces by direct picosecond laser ablation.
AB  - The performance of optical systems is typically improved by increasing the number
      of conventionally fabricated optical components (spheres, aspheres, and
      gratings). This approach is automatically connected to a system enlargement, as
      well as potentially higher assembly and maintenance costs. Hybrid optical
      freeform components can help to overcome this trade-off. They merge several
      optical functions within fewer but more complex optical surfaces, e.g., elements
      comprising shallow refractive/reflective and high-frequency diffractive
      structures. However, providing the flexibility and precision essential for their
      realization is one of the major challenges in the field of optical component
      fabrication. In this article we present tailored integrated machining techniques
      suitable for rapid prototyping as well as the fabrication of molding tools for
      low-cost mass replication of hybrid optical freeform components. To produce the
      different feature sizes with optical surface quality, we successively combine
      mechanical machining modes (ultraprecision micromilling and fly cutting) with
      precisely aligned direct picosecond laser ablation in an integrated fabrication
      approach. The fabrication accuracy and surface quality achieved by our integrated
      fabrication approach are demonstrated with profilometric measurements and
      experimental investigations of the optical performance.

PMID- 21743522
TI  - Ultrafast Yb:Y2SiO5 laser investigation based on a carbon nanotube absorber.
AB  - Transmission-type single-walled carbon nanotube saturable absorbers were
      successfully fabricated and used in a CW passively mode-locked Yb:Y2SiO5 laser
      for the first time to our knowledge. We obtained pulses as short as 1.1 ps around
      a center wavelength of 1058 nm. The average output power of 1.1 W was achieved at
      the repetition of 96.7 MHz; the corresponding peak power and energy of a single
      pulse was 10.3 kW and 11.4 nJ, respectively.

PMID- 21743523
TI  - Emission characteristics of photonic crystal light-emitting diodes.
AB  - Experimentally measured optical properties of photonic crystal LEDs are reported
      here. Photonic crystal and photonic quasi-crystal structures were fabricated on
      GaN epilayer LED wafer material using both direct-write electron beam lithography
      and nanoimprint lithography. Some of these structures were processed to make
      finished LEDs. Both electroluminescence and photoluminescence measurements were
      performed on these structures. Devices were characterized for their current
      voltage characteristics, emission spectra, far-field emission pattern, and
      angular emission pattern. These results are useful for fabricating photonic
      crystal LEDs and assessing their operational properties.

PMID- 21743524
TI  - Measurement of the two-photon absorption cross section by means of femtosecond
      thermal lensing.
AB  - We present a variation of the single-beam thermal lensing experiment to determine
      the two-photon absorption cross sections of classical fluorophores. The approach
      is based on comparison of two thermal lensing signals simultaneously induced by a
      one- and two-photon absorption process from a high-repetition-rate femtosecond
      laser system. As a consequence of this comparison, a simplified expression
      independent of the several experimental parameters is obtained. Additionally,
      because of the low incident power levels required, undesirable optical effects
      such as Kerr or Raman scattering are avoided. Our experimental results agree well
      with those recently published for luminescent methods, validating the approach.

PMID- 21743525
TI  - Measurement of shaft diameters by machine vision.
AB  - A machine vision method for accurately measuring the diameters of cylindrical
      shafts is presented. Perspective projection and the geometrical features of
      cylindrical shafts are modeled in order to enable accurate measurement of shaft
      diameters. Some of the model parameters are determined using a shaft of known
      diameter. The camera model itself includes radial and tangential distortions
      terms. Experiments were used to measure the accuracy of the proposed method and
      the effect of the position of the camera relative to the shaft, as well as other
      factors.

PMID- 21743526
TI  - Design of the double-telecentric high-aperture diffractive-refractive objectives.
AB  - The possibility for achieving optical performance of objectives, including a
      minimum amount of diffractive lenses, comparable to optical performance of
      multiple-lens conventional objectives for nanolithography, is considered. The
      problem of chromatism connected with using excimer lasers is solved by applying
      aspheric substrates that help to reduce both axial color and spherochromatic
      aberration.

PMID- 21743527
TI  - Interferometric investigation and simulation of refractive index in glass
      matrixes containing nanoparticles of varying sizes.
AB  - The relationship between refractive index and nanoparticle radii of cadmium
      selenide (CdSe) nanoparticles embedded within glass matrixes was investigated
      experimentally and by simulations. A homemade automated Michelson interferometer
      arrangement employing a rotating table and a He-Ne laser source at a wavelength
      of 632.8 nm determined the refractive index versus nanoparticle radii of embedded
      cadmium selenide (CdSe) nanoparticles. The refractive index was found to decrease
      linearly with nanoparticle radius increase. However, one sample showed a step
      increase in refractive index; on spectroscopic analysis, it was found that its
      resonant wavelength matched that of the He-Ne source wavelength. The simulations
      showed that two conditions caused the step increase in refractive index: low
      plasma frequency and matched sample and source resonances. This simple
      interferometer setup defines a new method of determining the radii of
      nanoparticles embedded in substrates and enables refractive index tailoring by
      modification of exact annealing conditions.

PMID- 21743528
TI  - Tunable solid-body elastomer lenses with electromagnetic actuation.
AB  - We present novel biconvex solid-body elastomer (polydimethylsiloxane) lenses,
      which can be tuned in focal length by using magnetic or mechanical actuation. The
      focal length change is induced by applying radial elastic strain and is
      investigated for different initial radii of curvature of the lenses and different
      actuation designs. In all cases, a linear correlation between induced strain and
      focal length tuning, in the range of about 10% (approximately 3 mm), is found.
      These results compare favorably with finite element simulations.

PMID- 21743529
TI  - Effect of focusing conditions on laser-induced shock waves at titanium-water
      interface.
AB  - The spatial and temporal evolution of laser-induced shock waves at a titanium
      water interface was analyzed using a beam deflection setup. The focusing
      conditions of the source laser were varied, and its effect onto the dynamics of
      shock waves was elucidated. For a tightly focused condition, the speed of the
      shock wave was ~6.4 Km/s, whereas for a defocused condition the velocities
      reduced to <3 km/s at the vicinity of the titanium-water interface. When the
      laser is focused a few millimeters above the target, i.e., within the water, the
      emission of dual shock waves was observed toward the rear side of the focal
      volume. These shock waves originate from the titanium-water interface as well as
      from the pure water breakdown region, respectively. The shock wave pressure is
      estimated from the shock wave velocity using the Newton's second law across a
      shock wave discontinuity. The shock wave pressure for a tightly focused condition
      was 18 GPa, whereas under a defocused condition the pressure experienced was <=1
      GPa in the proximity of target.

PMID- 21743530
TI  - Three-dimensional modeling using x-ray shape-from-silhouette.
AB  - We present the application of the shape-from-silhouette technique to reconstruct
      the three-dimensional profile of ancient handworks from their x-ray absorption
      images. The acquisition technique is similar to tomography, since the images are
      taken all around the object while it is rotated. Some reference points are placed
      on a small and light structure corotating with the object, and are acquired on
      the images for calibration and registration. The reconstruction algorithm gives
      finally the three-dimensional appearance of the handwork. We present the analysis
      of a bronze pendant of VI-VII century B.C. (Venetic area, Italy) completely
      hidden by corrosion products. The three-dimensional reconstruction shows that the
      pendant is a very elaborated piece, with two embraced figures that were
      completely invisible at the excavation.

PMID- 21743531
TI  - Sensitivity enhancement of grating interferometer based two-dimensional sensor
      arrays using two-wavelength readout.
AB  - Diffraction gratings integrated with microelectromechanical systems (MEMS)
      sensors offer displacement measurements with subnanometer sensitivity. However,
      the sensitivity of the interferometric readout may drop significantly based on
      the gap between the grating and the reference surface. A two-wavelength (2
      lambda) readout method was previously tested using a single MEMS sensor for
      illustrating increased displacement measurement capability. This work
      demonstrates sensitivity enhancement on a sensor array with large scale
      parallelization (~20,000 sensors). The statistical representation, which is
      developed to model sensitivity enhancement within a grating based sensor array,
      is supported by experimental results using a thermal sensor array. In the
      experiments, two lasers at different wavelengths (633 and 650 nm) illuminate the
      thermal sensor array from the backside, time-sequentially. The diffracted first
      order light from the array is imaged onto a single CCD camera. The target scene
      is reconstructed by observing the change in the first diffracted order
      diffraction intensity for both wavelengths. Merging of the data from two
      measurements with two lasers was performed by taking the larger of the two CCD
      measurements with respect to the reference image for each sensor. ~30% increase
      in the average sensitivity was demonstrated for a 160*120 pixel IR sensor array.
      Proposed architecture is also applicable to a variety of sensing applications,
      such as parallel biosensing and atomic force microscopy, for improved
      displacement measurements and enhanced sensitivity.

PMID- 21743532
TI  - Spectrally selective reflector surfaces for heat reduction in concentrator solar
      cells: modeling and applications of TiO2:Nb-based thin films.
AB  - The energy conversion efficiency of a conventional pn junction solar cell
      decreases as the temperature increases, and this may eventually lead to failures
      in the photovoltaic system, especially if it uses concentrated solar radiation.
      In this work, we show that spectrally selective reflector (SSR) surfaces can be
      important for reducing the heat buildup on passively cooled solar cells. We
      outline a computational scheme for optimizing DC magnetron-sputtered TiO2:Nb
      based SSRs tailored for silicon solar cells and find good agreement of the
      reflectance with an experimental realization of the optimal SSR. A figure of
      merit for SSRs has also been derived and applied to the experimental data.

PMID- 21743533
TI  - Evaluation and optimization of the optical performance of low-concentrating
      dielectric compound parabolic concentrator using ray-tracing methods.
AB  - We present a detailed design concept and optical performance evaluation of
      stationary dielectric asymmetric compound parabolic concentrators (DiACPCs) using
      ray-tracing methods. Three DiACPC designs, DiACPC-55, DiACPC-66, and DiACPC-77,
      of acceptance half-angles (0 degrees  and 55 degrees ), (0 degrees  and 66
      degrees ), and (0 degrees  and 77 degrees ), respectively, are designed in order
      to optimize the concentrator for building facade photovoltaic applications in
      northern latitudes (>55  degrees N). The dielectric concentrator profiles have
      been realized via truncation of the complete compound parabolic concentrator
      profiles to achieve a geometric concentration ratio of 2.82. Ray-tracing
      simulation results show that all rays entering the designed concentrators within
      the acceptance half-angle range can be collected without escaping from the
      parabolic sides and aperture. The maximum optical efficiency of the designed
      concentrators is found to be 83%, which tends to decrease with the increase in
      incidence angle. The intensity is found to be distributed at the receiver (solar
      cell) area in an inhomogeneous pattern for a wide range of incident angles of
      direct solar irradiance with high-intensity peaks at certain points of the
      receiver. However, peaks become more intense for the irradiation incident close
      to the extreme acceptance angles, shifting the peaks to the edge of the receiver.
      Energy flux distribution at the receiver for diffuse radiation is found to be
      homogeneous within +/-12% with an average intensity of 520 W/m2.

PMID- 21743534
TI  - Measurement of membrane rigidity on trapped unilamellar phospholipid vesicles by
      using differential confocal microscopy.
AB  - We use optical tweezers to trap a unilamellar phospholipid vesicle and measure
      the out-of-plane thermal fluctuations by using differential confocal microscopy.
      Bending moduli of the lipid membranes are calculated directly from the mean
      square values of the fluctuation amplitudes. Owing to the refractive index
      contrast between the inner and outer solutions of the vesicle, optical tweezers
      trap the vesicle laterally and improve the reliability of the measured
      fluctuation amplitudes along the optical axis. Bending moduli of membranes in gel
      or fluid phases obtained by the combination of differential confocal microscopy
      and optical tweezers are close to those reported previously. We also obtain the
      bending modulus of sphingomyelin membranes in the gel phase, which was not
      reported previously.

PMID- 21743535
TI  - Simplified design of thin-film polarizing beam splitter using embedded symmetric
      trilayer stack.
AB  - An analytically tractable design procedure is presented for a polarizing beam
      splitter (PBS) that uses frustrated total internal reflection and optical
      tunneling by a symmetric LHL trilayer thin-film stack embedded in a high-index
      prism. Considerable simplification arises when the refractive index of the high
      index center layer H matches the refractive index of the prism and its thickness
      is quarter-wave. This leads to a cube design in which zero reflection for the p
      polarization is achieved at a 45 degrees  angle of incidence independent of the
      thicknesses of the identical symmetric low-index tunnel layers L and L.
      Arbitrarily high reflectance for the s polarization is obtained at subwavelength
      thicknesses of the tunnel layers. This is illustrated by an IR Si-cube PBS that
      uses an embedded ZnS-Si-ZnS trilayer stack.

PMID- 21743536
TI  - Research on error control and compensation in magnetorheological finishing.
AB  - Although magnetorheological finishing (MRF) is a deterministic finishing
      technology, the machining results always fall short of simulation precision in
      the actual process, and it cannot meet the precision requirements just through a
      single treatment but after several iterations. We investigate the reasons for
      this problem through simulations and experiments. Through controlling and
      compensating the chief errors in the manufacturing procedure, such as removal
      function calculation error, positioning error of the removal function, and
      dynamic performance limitation of the CNC machine, the residual error convergence
      ratio (ratio of figure error before and after processing) in a single process is
      obviously increased, and higher figure precision is achieved. Finally, an
      improved technical process is presented based on these researches, and the
      verification experiment is accomplished on the experimental device we developed.
      The part is a circular plane mirror of fused silica material, and the surface
      figure error is improved from the initial lambda/5 [peak-to-valley (PV)
      lambda=632.8 nm], lambda/30 [root-mean-square (rms)] to the final lambda/40 (PV),
      lambda/330 (rms) just through one iteration in 4.4 min. Results show that a
      higher convergence ratio and processing precision can be obtained by adopting
      error control and compensation techniques in MRF.

PMID- 21743537
TI  - Active phase locking of fiber amplifiers using sine-cosine single-frequency
      dithering technique.
AB  - The sine-cosine single-frequency dithering technique for active phase locking of
      fiber amplifiers is presented for the first time to our knowledge. It has twice
      the phase control speed as the single-frequency dithering technique. Detailed
      theoretical development has been presented and the relevant experiment has been
      done. In the experiment, nine 10 W level fiber amplifiers are tiled into 3*3
      array and the total output power is about 100 W. The sine-cosine single-frequency
      dithering algorithm is run on a signal processor based on a field-programmable
      gate array for phase control on the fiber amplifiers. When the phase control
      system is in a closed loop, the fringe contrast of far-field intensity pattern is
      improved by more than 90% from 21% in an open loop, and the residual phase error
      is less than lambda/20.

PMID- 21743538
TI  - Nonaxial Strehl ratio of wavefront coding systems with a cubic phase mask.
AB  - An approximate expression of the peak position of the point-spread function (PSF)
      of wavefront coding systems with a cubic phase mask (CPM) is derived and verified
      by simulation results. An approach called the nonaxial Strehl ratio (NASR) is
      used to evaluate the performance of wavefront coding systems with defocus
      aberrations. The characteristics of the NASR are investigated. The relationships
      between the NASR and the similarity of out-of-focus modulation transfer function
      (MTF) and recoverability of blurred encoding images are presented, and some
      useful guidelines are given for the optimization of phase mask parameters
      according to these relationships.

PMID- 21743539
TI  - Validity of the thin mask approximation in extreme ultraviolet mask roughness
      simulations.
AB  - In the case of extreme ultraviolet (EUV) lithography, modeling has shown that
      reflector phase roughness on the lithographic mask is a significant concern due
      to the image plane speckle it causes and the resulting line-edge roughness on
      imaged features. Modeling results have recently been used to determine the
      requirements for future production worthy masks yielding the extremely stringent
      specification of 50 pm rms roughness. Owing to the scale of the problem in terms
      of memory requirements, past modeling results have been based on the thin mask
      approximation in this application. EUV masks, however, are inherently three
      dimensional (3D) in nature and thus the question arises as to the validity of the
      thin mask approximation. Here, we directly compare the image plane speckle
      calculation results using the fast two-dimensional thin mask model to rigorous
      finite-difference time-domain results and find the two methods to agree to within
      10% in the computation of the speckle magnitude and 20% in the computation of the
      line-edge roughness limited depth of focus. For both types of computation, the
      two-dimensional method provides a conservative estimate. The 3D modeling is also
      used to show that layer-to-layer correlated roughness is indeed the roughness
      metric of most concern.

PMID- 21743540
TI  - Optical and tribomechanical stability of optically variable interference security
      devices prepared by dual ion beam sputtering.
AB  - Optical security devices applied to banknotes and other documents are exposed to
      different types of harsh environments involving the cycling of temperature,
      humidity, chemical agents, and tribomechanical intrusion. In the present work, we
      study the stability of optically variable devices, namely metameric interference
      filters, prepared by dual ion beam sputtering onto polycarbonate and glass
      substrates. Specifically, we assess the color difference as well as the changes
      in the mechanical properties and integrity of all-dielectric and metal-dielectric
      systems due to exposure to bleach, detergent and acetone agents, and heat and
      humidity. The results underline a significant role of the substrate material, of
      the interfaces, and of the nature and microstructure of the deposited films in
      long term stability under everyday application conditions.

PMID- 21743541
TI  - Single-shot, dual-wavelength digital holography based on polarizing separation.
AB  - We describe what we believe to be a new digital holographic configuration that
      can be utilized for both single-shot, dual-wavelength, off-axis geometry and
      imaging polarimetry. To get the feasibility of the single-shot, dual-wavelength,
      off-axis geometry, a sample with a nominal step height of 1.34 MUm is used.
      Undesirable noises that strongly affect the measurement have been suppressed
      successfully by using a modified flat fielding method for the dual-wavelength
      scheme. And also, the experiment is conducted on a nanopattern sample on the
      basis of a single image acquisition to show the imaging polarimetry capability.
      The proposed scheme can provide a real-time solution for measuring three
      dimensional objects having a high abrupt height difference with moderate
      accuracy. Furthermore, it can be used as a fast polarization imaging measurement
      tool.

PMID- 21743542
TI  - Construction method of axially asymmetric lenses.
AB  - A method to find the optimal position of tilt surfaces to construct axially
      asymmetric lens systems is proposed. The tilt surface number is extended to the
      real number and included in the independent variables of the optimization.

PMID- 21743543
TI  - Effective reduction of the novel look-up table memory size based on a
      relationship between the pixel pitch and reconstruction distance of a computer
      generated hologram.
AB  - In this paper, we propose an approach, new to our knowledge, to effectively
      generate and reconstruct the resolution-enhanced computer-generated hologram
      (CGH) of three-dimensional (3-D) objects with a significantly reduced in memory
      size novel look-up table (N-LUT) by taking into account a relationship between
      the pixel pitch and reconstruction distance of the hologram pattern. In the
      proposed method, a CGH pattern composed of shifted versions of the principal
      fringe patterns (PFPs) with a short pixel pitch can be reconstructed just by
      using the CGH generated with a much longer pixel pitch by controlling the
      hologram reconstruction distance. Accordingly, the corresponding N-LUT memory
      size required for resolution-enhanced hologram patterns can be significantly
      reduced in the proposed method. To confirm the feasibility of the proposed
      method, experiments are carried out and the results are discussed.

PMID- 21743544
TI  - Measurement of Young's modulus in an elastic material using 3D digital
      holographic interferometry.
AB  - Digital holographic interferometry using three different illumination directions
      is applied to quantify in full field of view the deformation of an elastic
      membrane under a given vibration frequency. The technique allows the separation
      of the object microdisplacements components in the x, y, and z directions, and
      the resulting data is used to find the membrane Young's modulus. The latter was
      compared with the result obtained using the theory of thin plates for a clamped
      circular membrane under a uniformly distributed load, reaching a 95% agreement.
      Validation of the results between these methods shows the reliability of DHI to
      measure the mechanical properties of an elastic material.

PMID- 21743545
TI  - Comparison of algorithms used for optical characterization of multilayer optical
      coatings.
AB  - Two algorithms used for the on-line and off-line characterization of multilayer
      optical coatings are experimentally compared using test samples produced by two
      different deposition processes and different monitoring approaches. One of these
      algorithms, called the triangular algorithm, demonstrates its superiority in all
      considered situations. We performed experiments with multilayer samples formed by
      high-density thin films, which allowed us to neglect possible errors in the film
      refractive indices and concentrate only on errors in the thicknesses of the
      layers of the produced coatings.

PMID- 21743546
TI  - Remote nocturnal bird classification by spectroscopy in extended wavelength
      ranges.
AB  - We present optical methods at a wide range of wavelengths for remote
      classification of birds. The proposed methods include eye-safe fluorescence and
      depolarization lidar techniques, passive scattering spectroscopy, and infrared
      (IR) spectroscopy. In this paper we refine our previously presented method of
      remotely classifying birds with the help of laser-induced beta-keratin
      fluorescence. Phenomena of excitation quenching are studied in the laboratory and
      are theoretically discussed in detail. It is shown how the ordered
      microstructures in bird feathers induce structural "colors" in the IR region with
      wavelengths of around 3-6 MUm. We show that transmittance in this region depends
      on the angle of incidence of the transmitted light in a species-specific way and
      that the transmittance exhibits a close correlation to the spatial periodicity in
      the arrangement of the feather barbules. We present a method by which the
      microstructure of feathers can be monitored in a remote fashion by utilization of
      thermal radiation and the wing beating of the bird.

PMID- 21743547
TI  - Automated optimization of an aspheric light-emitting diode lens for uniform
      illumination.
AB  - In this paper, an automated optimization method in the sequential mode of ZEMAX
      is proposed in the design of an aspheric lens with uniform illuminance for an LED
      source. A feedback modification is introduced in the design for the LED extended
      source. The user-defined merit function is written out by using ZEMAX programming
      language macros language and, as an example, optimum parameters of an aspheric
      lens are obtained via running an optimization. The optical simulation results
      show that the illumination efficiency and uniformity can reach 83% and 90%,
      respectively, on a target surface of 40 mm diameter and at 60 mm away for a 1*1
      mm LED source.

PMID- 21743548
TI  - Quantitative Fourier analysis of schlieren masks: the transition from shadowgraph
      to schlieren.
AB  - In a schlieren setup, a lens system forms an image of the refractive index
      fluctuations of a transparent sample onto a matrix detector while an intensity
      mask is positioned in the Fourier plane of a collecting lens to perform the
      required spatial filtering. In the absence of the mask, the resulting technique
      is that of a shadowgraph. The two methods provide different information about the
      refractive index of transparent fluids and can be used both for visualization
      purposes and scattering measurements. Here, we describe the effect of the
      intensity mask on the technique transfer function, i.e., its ability to detect
      different spatial frequencies and show how the special cases of shadowgraph,
      schlieren, and the transition between the two can be derived. We also present
      experimental data that agree well with our predictions.

PMID- 21743549
TI  - Design and analysis of a phase modulator based on a metal-polymer-silicon hybrid
      plasmonic waveguide.
AB  - A plasmonic-hybrid-waveguide-based optical phase modulator is proposed and
      analyzed. The field enhancement in the low-index high-nonlinear polymer layer
      provides nanoscale optical confinement and a fast optical modulation speed. At
      2.5 V drive voltage, a pi phase shift can be obtained for a 13-MUm-long plasmonic
      waveguide. Because of its small capacitance and parasitic resistance, the
      modulation bandwidth can reach up to 100 GHz with a low power consumption of ~9
      fJ/bit. The plasmonic waveguide is connected to a silicon wire waveguide via an
      adiabatic taper with a coupling efficiency of ~91%. The phase modulator can find
      potential applications in optical telecommunication and interconnects.

PMID- 21743550
TI  - Temperature field analysis of single layer TiO2 film components induced by long
      pulse and short-pulse lasers.
AB  - To study the differences between the damaging of thin film components induced by
      long-pulse and short-pulse lasers, a model of single layer TiO(2) film components
      with platinum high-absorptance inclusions was established. The temperature rises
      of TiO(2) films with inclusions of different sizes and different depths induced
      by a 1 ms long-pulse and a 10 ns short-pulse lasers were analyzed based on
      temperature field theory. The results show that there is a radius range of
      inclusions that corresponds to high temperature rises. Short-pulse lasers are
      more sensitive to high-absorptance inclusions and long-pulse lasers are more
      easily damage the substrate. The first-damage decision method is drawn from
      calculations.

PMID- 21743551
TI  - Detectable distance calculations for a visual navigation system using a scanning
      semiconductor laser with electronic pumping.
AB  - Results of detectable distance calculations for a visual navigation system based
      on a scanning semiconductor laser with electronic pumping (SSLEP) are presented.
      A semiconductor crystal in the laser is pumped with an electron beam, which is
      scanned across the crystal in the television-frame scan mode. The navigation
      system forms three orientation sectors with radiation wavelengths lambda=0.52,
      0.57, and 0.63 MUm. Herein, calculations of energetic characteristics of output
      radiation are performed for the navigation system described above. The
      calculations were performed using the Range software package, which considers
      microphysical and optical characteristics of aerosol and observation path
      geometry for the case of coastal environment. Finally, comparison of results of
      the calculations with data obtained in marine and flight experiments is
      presented. It is demonstrated that minor discrepancies between calculated and
      measured values of detectable distance are observed in the coastal haze at lower
      values of meteorological visibility range S(m). As S(m) increases, the
      discrepancies become significant.

PMID- 21743552
TI  - Alternative configuration for an optical ring resonator angular rate sensor by
      using a standard laser diode.
AB  - In this work, we present an alternative approach to angular velocity optical
      sensing based on two-ring resonators. This configuration admits the use of a
      standard laser diode source (0.1 nm, 10,000 MHz, FWHM) reaching higher
      sensitivities when narrow spectral laser sources (1 MHz, FWHM) are used. We
      compare this configuration with the standard single-ring resonator angular rate
      sensor (SRARS), which must use a narrow laser at input. Finally, we conclude that
      the sensitivity of this new approach can also be enhanced by coupling high-power
      broadband laser sources in a large range (from 1 degrees /h to 10,000 degrees
      /h), reaching performance similar to that of a standard SRARS configuration.

PMID- 21743553
TI  - Instantaneous phase method for readout signal processing of body dithered ring
      laser gyro.
AB  - The readout signal of a body dithered ring laser gyro contains both useful
      information and the dither component. The dither component must be removed to get
      the useful information. The dither stripping method can get the useful
      information without latency. But the quadrature demodulator only has 1/4 pulse
      resolution, which means that the quantization noise will limit the short-term
      accuracy. The effect and the property of quantization noise are analyzed in
      detail. Taking advantage of high-speed analog-to-digital conversion (ADC), the
      analog values of the two beat frequency signals in quadrature are sampled. A
      novel instantaneous phase method is introduced, which can get the residual phase
      besides 4* resolution and the quantization noise can be removed radically. The
      Allan variance analysis of experimental results shows that the quantization noise
      coefficient using this method is only 1/7 of that using the original 4*
      resolution method.

PMID- 21743554
TI  - Quadrant photodetector sensitivity.
AB  - A quantitative theoretical analysis of the quadrant photodetector (QPD)
      sensitivity in position measurement is presented. The Gaussian light spot
      irradiance distribution on the QPD surface was assumed to meet most of the real
      life applications of this sensor. As the result of the mathematical treatment of
      the problem, we obtained, in a closed form, the sensitivity function versus the
      ratio of the light spot 1/e radius and the QPD radius. The obtained result is
      valid for the full range of the ratios. To check the influence of the finite
      light spot radius on the interaxis cross talk and linearity, we also performed a
      mathematical analysis to quantitatively measure these types of errors. An optimal
      range of the ratio of light spot radius and QPD radius has been found to
      simultaneously achieve low interaxis cross talk and high linearity of the sensor.

PMID- 21743555
TI  - Measurement of a cross-sectional profile of a thread gauge using a sinusoidally
      vibrating interference pattern.
AB  - A sinusoidally vibrating interference pattern (SVIP) is used as an exact spatial
      scale in order to measure a cross-sectional profile of a thread gauge. The SVIP
      is projected on the thread gauge surface, and lights diffracted and reflected
      from the end points of the thread gauge surface are extracted by spatial
      frequency filtering in an imaging system to make an image of the end points whose
      positions are decided by the peak positions of amplitude distributions in the
      image. The coordinates of the end points or the cross-sectional profile of the
      thread gauge is obtained from the phases measured at the positions of the end
      points, phase distribution of the SVIP on a CCD image sensor, and the pixel
      positions of the CCD image sensor.

PMID- 21743556
TI  - Strong infrared radiation through passive dispersive wave generation and its
      control.
AB  - We observe strong infrared (IR) radiation as a result of passive dispersive wave
      generation for a realistic microstructured fiber having two zero-dispersion
      wavelengths. The IR radiation frequency can be suitably controlled by varying the
      operational wavelength, which falls in the first normal dispersion regime. The
      amplitude of the radiation can be significantly increased by introducing a
      suitable amount of chirp in the input pulse. This strong phase-matching radiation
      can be considered as an alternative solution for the IR laser for different
      applications.

PMID- 21743557
TI  - Reference surface calibration of a Fizeau interferometer through even/odd
      synthesis.
AB  - We propose an even-/odd-synthesis method for the elimination of additional
      aberration caused by misalignment or environmental vibration during the
      calibration of a Fizeau interferometer reference surface (RS). The odd and even
      parts of an RS can be obtained, because surface errors could be divided into
      rotationally symmetric and nonrotationally symmetric terms. We then propose a
      least-squares algorithm with a dual-objective optimization function for
      calibration of the measurement results at the confocal position. Finally, a
      complete RS can be eventually obtained by synthesizing the odd and even parts of
      the RS. It has been verified through experiments that the measurement
      repeatability of the PV value is better than 0.003lambda, and the root-mean
      square value is better than 0.0003lambda.

PMID- 21743558
TI  - Detection of chloride in reinforced concrete using a dualpulsed laser-induced
      breakdown spectrometer system: comparative study of the atomic transition lines
      of Cl I at 594.85 and 837.59 nm.
AB  - The presence of chloride in reinforced concrete can cause severe damage to the
      strength and durability of buildings and bridges. The detection of chloride in
      concrete structures at early stages of the corrosion buildup process is,
      therefore, very important. However, detection of chlorine in trace amounts in
      concrete is not a simple matter. A dual-pulsed laser-induced breakdown
      spectrometer (LIBS) has been developed at our laboratory for the detection of
      chloride contents in reinforced concrete by using two atomic transition lines of
      neutral chlorine (Cl I) at 594.8 and 837.5 nm. A calibration curve was also
      established by using standard samples containing chloride in known concentration
      in the concrete. Our dual-pulsed LIBS system demonstrated a substantial
      improvement in the signal level at both wavelengths (594.8 and 837.5 nm).
      However, the new atomic transition line at 594.8 nm shows a significant
      improvement compared to the line at 837.5 nm in spite of the fact that the
      relative intensity of the former is 0.1% of the latter. This weak signal level of
      the 837.5 nm transition line of chlorine can be attributed to some kind of self
      absorption process taking place in the case of the concrete sample.

PMID- 21743559
TI  - Influences of the thickness, misalignment, and dispersion of the Savart
      polariscope on the optical path difference and spectral resolution in the
      polarization interference imaging spectrometer.
AB  - After reviewing the spectrum-dividing principle of the Savart polariscope (SP) in
      the polarization interference imaging spectrometer (PIIS) that we developed, we
      analyze the influences of the thickness, misalignment, and dispersion of the SP
      on the optical path difference (OPD). The theoretical expression of the OPD for
      the misalignment of the SP optical axis is deduced, and the OPD is analyzed when
      the incident plane is parallel, at 45 degrees , or orthogonal to the principal
      section of the left plate of the SP. The selective thickness of the single Savart
      plate is analyzed when it is placed at the ideal and misalignment positions. The
      influence of dispersion of the SP on the OPD is analyzed when the misalignment
      error is +/-1'. The relationships between the OPD and wavelength are simulated
      and validated with experiments. This work can provide theoretical and practical
      guidance for the design, calibration, modulation, innovation, experiment, and
      engineering of the PIIS.

PMID- 21743560
TI  - Electric-field sensors utilizing coupling between a D-fiber and an electro-optic
      polymer slab.
AB  - This paper provides a detailed analysis of electric field sensing using a slab
      coupled optical fiber sensor (SCOS). This analysis explains that the best
      material for the slab waveguide is an inorganic material because of the low RF
      permittivity combined with the high electro-optic coefficient. The paper also
      describes the fabrication and testing of a SCOS using an AJL chromophore in
      amorphous polycarbonate. The high uniform polymer slab waveguide is fabricated
      using a hot embossing process to create a slab with a thickness of 50 MUm. The
      fabricated polymer SCOS was characterized to have a resonance slope of
      DeltaP/Deltalambda=6.83E5 W/m and a resonance shift of Deltalambda/E=1.47E-16
      m(2)/V.

PMID- 21743561
TI  - Superfocusing effect in the chain of silver nanorods.
AB  - A chain of three silver nanorods with progressively decreasing sizes and
      separations is designed to focus the electric fields around the small nanorods.
      The optical properties of the chain of silver nanorods are investigated by the
      discrete dipole approximation method. The results show that, compared with the
      individual small nanorod and the chain of two nanorods, many enhanced electric
      fields are focused around the small nanorod of the chain of three nanorods due to
      the electric field couplings between adjacent nanorods. Therefore, the design of
      the chain of three nanorods provides a way to obtain stronger electric fields. In
      addition, how the structural parameters of the chain of three nanorods affect
      their optical properties is also studied.

PMID- 21743562
TI  - Monitoring the statistics of turbulence: Fried parameter estimation from the
      wavefront sensor measurements.
AB  - Near-the-ground laser communication systems must operate in the presence of
      strong atmospheric turbulence. The effects of atmospheric turbulence on the laser
      beam that are relevant to optical communications are a broadening of the laser
      footprint, random jitter of the laser beam, and high spatial frequency intensity
      fluctuations referred to as scintillation. The overall goal of our program is to
      improve the performance and extend the range of optical communications systems by
      exploring the use of adaptive optics and channel coding. Knowledge of the
      turbulence conditions and the ability to describe its properties are the key
      aspects to make these improvements effective. The developed multiphase approach
      is directed to statistically describe atmospheric turbulence based on results
      derived from experimentally collected data. Statistics of Fried parameter r(0) is
      derived from 6 TB of data collected over 50 days, and under various day and night
      atmospheric conditions. Significant fluctuations of r(0) are found with the
      values ranging from 2 mm and up to 15 cm, corresponding to the significant
      structure function Cn2 fluctuations from 7.4*10(-14) to 8.1*10(-16).

PMID- 21743563
TI  - Site-specific multipoint fluorescence measurement system with end-capped optical
      fibers.
AB  - We present the development and implementation of a spatially and spectrally
      resolved multipoint fluorescence correlation spectroscopy (FCS) system utilizing
      multiple end-capped optical fibers and an inexpensive laser source. Specially
      prepared end-capped optical fibers placed in an image plane were used to both
      collect fluorescence signals from the sample and to deliver signals to the
      detectors. The placement of independently selected optical fibers on the image
      plane was done by monitoring the end-capped fiber tips at the focus using a CCD,
      and fluorescence from specific positions of a sample were collected by an end
      capped fiber, which could accurately represent light intensities or spectral data
      without incurring any disturbance. A fast multipoint spectroscopy system with a
      time resolution of ~1.5 ms was then implemented using a prism and an electron
      multiplying charge coupled device with a pixel binning for the region of
      interest. The accuracy of our proposed system was subsequently confirmed by
      experimental results, based on an FCS analysis of microspheres in distilled
      water. We expect that the proposed multipoint site-specific fluorescence
      measurement system can be used as an inexpensive fluorescence measurement tool to
      study many intracellular and molecular dynamics in cell biology.

PMID- 21743564
TI  - Dispersion-optimized optical fiber for high-speed long-haul dense wavelength
      division multiplexing transmission.
AB  - Four non-zero-dispersion-shifted fibers with almost the same large effective area
      (A(eff)) and optimized dispersion properties are realized by novel index profile
      designing and modified vapor axial deposition and modified chemical vapor
      deposition processes. An A(eff) of greater than 71 MUm(2) is obtained for the
      designed fibers. Three of the developed fibers with positive dispersion are
      improved by reducing the 1550 nm dispersion slope from 0.072 ps/nm(2)/km to 0.063
      ps/nm(2)/km or 0.05 ps/nm(2)/km, increasing the 1550 nm dispersion from 4.972
      ps/nm/km to 5.679 ps/nm/km or 7.776 ps/nm/km, and shifting the zero-dispersion
      wavelength from 1500 nm to 1450 nm. One of these fibers is in good agreement with
      G655D and G.656 fibers simultaneously, and another one with G655E and G.656
      fibers; both fibers are beneficial to high-bit long-haul dense wavelength
      division multiplexing systems over S-, C-, and L-bands. The fourth developed
      fiber with negative dispersion is also improved by reducing the 1550 nm
      dispersion slope from 0.12 ps/nm(2)/km to 0.085 ps/nm(2)/km, increasing the 1550
      nm dispersion from -4 ps/nm/km to -6.016 ps/nm/km, providing facilities for a
      submarine transmission system. Experimental measurements indicate that the
      developed fibers all have excellent optical transmission and good macrobending
      and splice performances.

PMID- 21743565
TI  - Modeling max-of-N fluence distribution using measured shot-to-shot beam contrast.
AB  - We have found the local temporal shot-to-shot variation of the NIF high-energy
      laser system to be relatively constant (~3.4% to 4.2% of the mean fluence). We
      have developed a statistical model that predicts the maximum fluence distribution
      any particular location will be exposed to after N independent shots (the so
      called max-of-N fluence distribution) using the measured shot-to-shot variance;
      this method allows for an estimate of maximum optics fluence exposure.

PMID- 21743566
TI  - Influence of vibration disturbance during polarization coupling measurement of
      polarization-maintaining fiber.
AB  - The principle of the mode cross coupling in polarization-maintaining fiber based
      on white-light interferometry was analyzed. The method of measuring the
      polarization mode coupling with a spatial Michelson interferometer was presented.
      Analysis and emulation were carried out for the vibration disturbance signal
      caused by the mechanical scanning and the influence the vibration imposed on the
      judgment of coupling intensity. The interference signal envelope is extracted by
      a Hilbert transform and fitted by a Gaussian least-squares method under the
      different scanning speed. It is indicated that the detection accuracy varies with
      the vibration amplitude, which varies with scanning speed. The best scanning
      speed of the system should be from 0.7 mm/s to 0.9 mm/s to achieve the minimum
      detection error.

PMID- 21743567
TI  - Nonnull interferometer simulation for aspheric testing based on ray tracing.
AB  - The nonnull interferometric method that employs a partial compensation system to
      compensate for the longitude aberration of the aspheric under test and a reverse
      optimization procedure to correct retrace errors is a useful technique for
      general aspheric testing. However, accurate system modeling and simulation are
      required to correct retrace errors and reconstruct fabrication error of the
      aspheric. Here, we propose a ray-tracing-based method to simulate the nonnull
      interferometer, which calculates the optical path difference by tracing rays
      through the reference path and the test path. To model a nonrotationally
      symmetric fabrication error, we mathematically represent it with a set of Zernike
      polynomials (i.e., Zernike deformation) and derive ray-tracing formulas for the
      deformed surface, which can also deal with misalignment situations (i.e., a
      surface with tilts and/or decenters) and thus facilitates system modeling
      extremely. Simulation results of systems with (relatively) large and small
      Zernike deformations and their comparisons with the lens design program Zemax
      have demonstrated the correctness and effectiveness of the method.

PMID- 21743568
TI  - Modeling of through-focus aerial image with aberration and imaginary mask edge
      effects in optical lithography simulation.
AB  - Aerial image through focus in the presence of aberrations and electromagnetic
      edge effects modeled by adding +/-pi/2 phase at pattern edges is expanded by a
      quadratic equation with respect to focus. The quadratic equation is expressed by
      four coefficients that are adequately independent of both mask layout and the
      variations in the optical setting in projection printing, thus saving the
      computation cost of the quadratic fit for each individual layout edge position in
      a new mask pattern or variation from a nominal optical setting. The error of this
      method is less than 1% for any typical integrated circuit features. This accuracy
      holds when the defocus is less than one Rayleigh unit (0.5lambda/NA(2), where
      lambda is a wavelength and NA is the numerical aperture) and the root mean square
      of the existing aberration is less than 0.02lambda, which encompasses current
      lithography practice. More importantly, the method is a foundation for future
      first-cut accurate algebraic imaging models that have sufficient speed for
      assessing the desired or undesired changes in the through-focus images of
      millions of features as the optical system conditions change. These optical
      system changes occur naturally across the image field, and aberration levels are
      even programmed in tuning modern tooling to compensate for electromagnetic mask
      edge effects.

PMID- 21743569
TI  - Holographic display with tilted spatial light modulator.
AB  - In this paper, we analyze a holographic display system utilizing a phase-only
      spatial light modulator (SLM) based on liquid crystal on silicon (LCoS). An LCoS
      SLM works in reflection, and, in some applications, it is convenient to use with
      an inclined illumination. Even with a highly inclined illumination, the
      holographic display is capable of good-quality image generation. We show that the
      key to obtain high-quality reconstructions is the tilt-dependent calibration and
      algorithms. Typically, an LCoS SLM is illuminated with a plane wave with normal
      wave vector. We use inclined illumination, which requires development of new
      algorithms and display characterization. In this paper we introduce two
      algorithms. The first one is designed to process a digital hologram captured in
      CCD normal configuration, so it can be displayed in SLM tilted geometry, while
      the second one is capable of synthetic hologram generation for tilted SLM
      configuration. The inclined geometry asymmetrically changes the field of view of
      a holographic display. The presented theoretical analysis of the aliasing effect
      provides a formula for the field of view as a function of SLM tilt. The incidence
      angle affects SLM performance. Both elements of SLM calibration, i.e., pixel
      phase response and wavefront aberrations, strongly depend on SLM tilt angle. The
      effect is discussed in this paper. All of the discussions are accompanied with
      experimental results.

PMID- 21743570
TI  - Automated imaging, identification, and counting of similar cells from digital
      hologram reconstructions.
AB  - This paper presents our method, which simultaneously combines automatic imaging,
      identification, and counting with the acquisition of morphological information
      for at least 1000 blood cells from several three-dimensional images of the same
      sample. We started with seeking parameters to differentiate between red blood
      cells that are similar but different with respect to their development stage,
      i.e., mature or immature. We highlight that these cells have different
      diffractive patterns with complementary central intensity distribution in a given
      plane along the propagation axis. We use the Fresnel approximation to simulate
      propagation through cells modeled as spheroid-shaped phase objects and to find
      the cell property that has the dominant influence on this behavior. Starting with
      images obtained in the reconstruction step of the digital holographic microscopy
      technique, we developed a code for automated simultaneous individual cell image
      separation, identification, and counting, even when the cells are partially
      overlapped on a slide, and accurate measuring of their morphological features. To
      find the centroids of each cell, we propose a method based on analytical
      functions applied at threshold intervals. Our procedure separates the mature from
      the immature red blood cells and from the white blood cells through a decision
      based on gradient and radius values.

PMID- 21743571
TI  - Zonal wavefront sensor with reduced number of rows in the detector array.
AB  - In this paper, we describe a zonal wavefront sensor in which the photodetector
      array can have a smaller number of rows. The test wavefront is incident on a two
      dimensional array of diffraction gratings followed by a single focusing lens. The
      periodicity and the orientation of the grating rulings of each grating can be
      chosen such that the +1 order beam from the gratings forms an array of focal
      spots in the detector plane. We show that by using a square array of zones, it is
      possible to generate an array of +1 order focal spots having a smaller number of
      rows, thus reducing the height of the required detector array. The phase profile
      of the test wavefront can be estimated by measuring the displacements of the +1
      order focal spots for the test wavefront relative to the +1 order focal spots for
      a plane reference wavefront. The narrower width of the photodetector array can
      offer several advantages, such as a faster frame rate of the wavefront sensor, a
      reduced amount of cross talk between the nearby detector zones, and a decrease in
      the maximum thermal noise. We also present experimental results of a proof-of
      concept experimental arrangement using the proposed wavefront sensing scheme.

PMID- 21743572
TI  - Terahertz tomographic imaging of XVIIIth Dynasty Egyptian sealed pottery.
AB  - A monochromatic millimeter-wave imaging system coupled with an infrared
      temperature sensor has been used to investigate historic objects preserved at the
      Museum of Aquitaine (France). In particular, two-dimensional and three
      dimensional analyses have been performed in order to reveal the internal
      structure of nearly 3500-year-old sealed Egyptian jars.

PMID- 21743573
TI  - Compensation of FM-to-AM conversion in high-power lasers.
AB  - FM-to-AM conversion in the ninth beam of the Shen Guang II laser system with
      sinusoidal phase-modulated spectra is calculated and analyzed. The simulations
      show that the intensity modulation at 3omega is much more serious compared to the
      other wavebands and it is mostly induced by the frequency conversion system
      rather than the amplification chain. The compensation effects of FM-to-AM
      conversion in the frequency conversion system by angular dispersion grating and
      cascaded crystals are numerically simulated and compared. Compared to the
      cascaded crystals, the angular dispersion grating could maintain higher frequency
      conversion efficiency with wide spectral width and offer a higher dynamic range
      of compensation effectiveness versus fundamental laser intensity. Combined with a
      precompensation filter before the amplification chain, FM-to-AM conversion at
      3omega could be eliminated.

PMID- 21743574
TI  - Design and optimization of liquid core optical ring resonator for refractive
      index sensing.
AB  - This study performs a detailed theoretical analysis of refractive index (RI)
      sensors based on whispering gallery modes (WGMs) in liquid core optical ring
      resonators (LCORRs). Both TE- and TM-polarized WGMs of various orders are
      considered. The analysis shows that WGMs of higher orders need thicker walls to
      achieve a near-zero thermal drift, but WGMs of different orders exhibit a similar
      RI sensing performance at the thermostable wall thicknesses. The RI detection
      limit is very low at the thermostable thickness. The theoretical predications
      should provide a general guidance in the development of LCORR-based thermostable
      RI sensors.

PMID- 21743575
TI  - Method to reduce errors of droplet sizing based on the ratio of fluorescent and
      scattered light intensities (laser-induced fluorescence/Mie technique).
AB  - The droplet sizing accuracy of the laser technique, based on the ratio of laser
      induced fluorescence (LIF) and scattered light (Mie) intensities from droplets,
      is examined. We develop an analytical model of the ratio of fluorescent to
      scattered light intensities of droplets, which shows that the LIF/Mie technique
      is susceptible to sizing errors that depend on the mean droplet size and the
      spread of the droplet size distribution. The sizing uncertainty due to the
      oscillations of the scattered light intensity as a function of droplet size is
      first quantified. Then, a new data processing method is proposed that can improve
      the sizing uncertainty of the technique for the sprays that were examined in this
      study by more than 5% by accounting for the size spread of the measured droplets,
      while improvements of 25% are possible when accounting for the mean droplet size.
      The sizing accuracy of the technique is evaluated in terms of the refractive
      index of liquid, scattering angle, and dye concentration in the liquid. It is
      found that the proposed approach leads to sizing uncertainty of less than 14%
      when combined with light collection at forward scattering angles close to 60
      degrees  and the lowest fluorescent dye concentration in the liquid for all
      refractive indices.

PMID- 21743576
TI  - Multispectral imaging axicons.
AB  - Large-aperture linear diffractive axicons are optical devices providing
      achromatic nondiffracting beams with an extended depth of focus when illuminated
      by white light sources. Annular apertures introduce chromatic foci separation,
      making chromatic imaging possible despite important radiometric losses. Recently,
      a new type of diffractive axicon has been introduced, by multiplexing concentric
      annular axicons with appropriate sizes and periods, called a multiple annular
      linear diffractive axicon (MALDA). This new family of conical optics combines
      multiple annular axicons in different ways to optimize color foci recombination,
      separation, or interleaving. We present different types of MALDA, give an
      experimental illustration of the use of these devices, and describe the
      manufacturing issues related to their fabrication to provide color imaging
      systems with long focal depths and good diffraction efficiency. Application to
      multispectral image analysis is discussed.

PMID- 21743577
TI  - Implementation of phase-shift patterns using a holographic projection system with
      phase-only diffractive optical elements.
AB  - We proposed a method to implement spatial phase-shift patterns with
      subdiffraction limited features through a holographic projection system. The
      input device of the system displayed phase-only diffractive optical elements that
      were calculated using the iterative Fourier-transform algorithm with the dummy
      area method. By carefully designing the target patterns to the algorithm, the
      diffractive optical elements generated the Fourier-transformed images containing
      the phase-shift patterns in which the widths of dark lines were smaller than the
      diffraction limit. With these demonstrations, we have successfully shown that the
      near-field phase-shift lithographic technique can be realized through an
      inexpensive maskless lithographic system and can still achieve subdiffraction
      limited images.

PMID- 21743578
TI  - Creating three-dimensional lattice patterns using programmable Dammann gratings.
AB  - We demonstrate the creation of a three dimensional (3D) lattice of focus spots
      using a 3D Dammann grating structure. Such a 3D lattice of focus spots can be
      used for probing 3D structures or for creating 3D photonic crystal structures in
      optically sensitive media. Experimental results are included where the patterns
      are encoded onto a programmable liquid crystal display. We demonstrate the
      generation of five planar arrays each having 6*6 points surrounding another set
      of four planar arrays each having 5*5 points with a single pattern.

PMID- 21743579
TI  - Vision method of inspecting missing fastening components in high-speed railway.
AB  - The increasing train speed on railways generates an urgent need for more powerful
      automatic inspection of railway tracks, including real-time fastening component
      inspection. To obtain better high-speed performance with lower cost, this paper
      has proposed a novel structured light method based on motion image (SLMMI) for
      moving object inspection. The motion images in the proposed method are
      insensitive to motion, abundant with information, and easy to process, resulting
      in a low performance requirement of the hardware. Compared to the conventional
      unstructured light method and structured light method, the proposed method
      inherits the virtues of both thus offering a fresh perspective when inspecting
      missing fastening components on high-speed railways. By using the SLMMI and the
      recognition method based on a neural network, the experimental results yield good
      performance in terms of speed and accuracy. Furthermore, the robustness of the
      proposed method is also discussed and simulated by adding typical interferences,
      such as ambient light, vibration, and obstacles.

PMID- 21743580
TI  - A nonlinear unmixing method in the infrared domain.
AB  - This paper presents the physical principle of a new (to our knowledge) unmixing
      method to retrieve optical properties (reflectance and emissivity) and surface
      temperatures over a heterogeneous and a folded landscape using hyperspectral and
      multiangular airborne images acquired with high spatial resolution. In fact, over
      such a complex scene, the linear mixing model of the reflectance commonly used in
      the reflective domain is no longer valid in the IR range for the two following
      reasons: multiple reflections due to the three-dimensional (3D) structure and the
      radiative phenomenon introduced by the temperature by way of the black body law.
      Thus, to solve this nonlinear unmixing problem, a new physical model of
      aggregation is used. Our model requires as inputs knowledge of the 3D scene
      structure and the spatial contribution of each material in the scene. Each
      elementary scene element is characterized by its optical properties, and its
      temperature, spectral, and multiangular acquisitions are required. This paper
      focuses only on the theoretical feasibility of such a method. In addition, an
      analysis is conducted evaluating the impact of the misregistration between the
      radiometric image and its digital terrain model, estimating a threshold of the
      relative importance of every elementary material to retrieve its corresponding
      optical properties and temperature. The results show that the 3D geometry must be
      accurately known (accuracy of 1 m for a spatial resolution of 20 m), and the
      relative contribution of material in the mixed area must be above 15% to retrieve
      its surface temperature with an accuracy better than 1 K. So, this method is
      applied on three different landscapes (heterogeneous flat surface, V shape, and
      urban canyon), and the results exhibit performances better than 1% for optical
      properties and 1 K for surface temperatures.

PMID- 21743581
TI  - Optical modeling of Fresnel zoneplate microscopes.
AB  - Defect free masks remain one of the most significant challenges facing the
      commercialization of extreme ultraviolet (EUV) lithography. Progress on this
      front requires high-performance wavelength-specific metrology of EUV masks,
      including high-resolution and aerial-image microscopy performed near the 13.5 nm
      wavelength. Arguably the most cost-effective and rapid path to proliferating this
      capability is through the development of Fresnel zoneplate-based microscopes.
      Given the relative obscurity of such systems, however, modeling tools are not
      necessarily optimized to deal with them and their imaging properties are poorly
      understood. Here we present a modeling methodology to analyze zoneplate
      microscopes based on commercially available optical modeling software and use the
      technique to investigate the imaging performance of an off-axis EUV microscope
      design. The modeling predicts that superior performance can be achieved by
      tilting the zoneplate, making it perpendicular to the chief ray at the center of
      the field, while designing the zoneplate to explicitly work in that tilted plane.
      Although the examples presented here are in the realm of EUV mask inspection, the
      methods described and analysis results are broadly applicable to zoneplate
      microscopes in general, including full-field soft-x-ray microscopes routinely
      used in the synchrotron community.

PMID- 21743582
TI  - Dynamic tomography with a priori information.
AB  - We present "dynamic tomography" algorithms that allow for the high-resolution,
      time-resolved imaging of dynamic (i.e., continuously time evolving) complex
      systems at existing x-ray micro-CT facilities. The behavior of complex systems is
      constrained by the underlying physics. By exploiting a priori knowledge of the
      geometry of the physical process being studied to allow the use of sophisticated
      iterative reconstruction techniques that incorporate constraints, we improve on
      current frame rates by at least an order of magnitude. This allows time-resolved
      imaging of previously intractable processes, such as two-phase fluid flow. We
      present reconstructions from experimental data collected at the Australian
      National University x-ray micro-CT facility.

PMID- 21743583
TI  - High-accuracy three-dimensional shape acquisition of a large-scale object from
      multiple uncalibrated camera views.
AB  - Acquiring a high-accuracy three-dimensional (3D) shape of a large-scale object
      from multiple uncalibrated camera views remains a big challenge, since a
      considerable number of images is required to cover the entire surface; the use of
      multiple images could, however, result in accumulative errors from each processed
      image. Here error propagation rules in the 3D reconstruction process have been
      deduced on the basis of the traditional dual-view reconstruction method. We
      propose a method that can control the accumulative errors by reducing the times
      of coordinate transformation with common-view-based dual-view reconstruction.
      This method involves constructing an image network composed of many image groups,
      each of which contains a common view. A baseline threshold method is introduced
      to construct a high-quality image network, and the sums or reprojection residual
      of all the common points is proposed to assess the validity of the solutions of
      the orientation. Experiments carried out with both synthetic and real images
      demonstrate that the proposed method can handle the accumulative error problem
      with robust and highly accurate results.

PMID- 21743584
TI  - Square-wave retarder for polarization computer-generated holography.
AB  - An etched calcite square-wave retarder is designed, fabricated, and demonstrated
      as an illuminator for an interlaced polarization computer-generated hologram
      (PCGH). The calcite square-wave retarder enables alternating columns of
      orthogonal linear polarizations to illuminate the interlaced PCGH. Together,
      these components produce a speckled, tangentially polarized PCGH diffraction
      pattern with a measured ratio of polarization of 84% and a degree of linear
      polarization of 0.81. An experimental alignment tolerance analysis is also
      reported.

PMID- 21743585
TI  - Photothermal delivery of microscopic objects via convection flows induced by
      laser beam from fiber tip.
AB  - We report a photothermal delivery of microscopic objects based on convection
      flows at the surface of water. The convection flows were induced by photothermal
      effect through a laser beam of 1.55 MUm wavelength from a fiber tip. A 206 MUm
      diameter oil drop was delivered forward and backward by changing the laser beam
      at a power of 28.5-40 mW. In addition, the delivery has been further demonstrated
      with a cluster of carbon and red blood cells at the laser powers of 14 and 20 mW,
      respectively.

PMID- 21743586
TI  - Correlation of stellar scintillation in different photometric bands.
AB  - Theoretical relations were obtained to calculate the correlation of stellar
      scintillation, when a star is measured simultaneously in two different
      photometric bands (channels). Differential color scintillation and the respective
      indices are proposed for practical evaluation of the correlation. Asymptotic
      dependence for the case of an infinitely small receiving aperture is derived and
      analyzed. The effect of atmospheric dispersion, which transforms the color
      differences into spatial differences, is examined. Additionally, the effect of
      the deviation of real optical turbulence from Kolmogorov turbulence is estimated.
      The obtained relations were compared with simultaneous measurements in three
      photometric bands and different receiving apertures in the range of 1 to 15 cm.
      It is shown that the measurements and calculated estimations of the color
      scintillation agree well.

PMID- 21743587
TI  - [Pre-hospital treatment of ophidian accidents: review, update, and current
      problems].
AB  - Mythic, out-dated, ambiguous and sometimes iatrogenic procedures, still remain in
      pre-hospital and hospital ophidian accident treatment. Errors, omissions and
      ignorance make ophidian accidents appear more dangerous than they truly are,
      resulting in a general public contempt toward snakes. Here we present an updated
      review of current knowledge on pre-hospital and hospital treatment of ophidian
      bite incidents, including indications, recommendations and logic errors. We
      describe an appropriate treatment for native Mexican poisonous snakebites using
      fabotherapics, based on our experience. Adequate initial pre-hospital and
      hospital management is crucial for a successful outcome of this medical
      emergency. We describe the state of the art in snake bite research discussing
      those procedures where research is needed to implement them either by the
      patient, first responders, paramedics and doctors. We suggest proposals to
      achieve even more efficient management of fabotherapics based on support
      networks. Finally, we emphasize prevention as the main subject of venom bite
      treatment, as it is always more adequate and economic to invest in prevention
      than to spend on mitigation during emergency and recovery.

PMID- 21743588
TI  - [Urbanization, megalopolization and mortality from birth defects in children
      under five years of age in Mexico].
AB  - OBJECTIVES: To identify the spatial-geographical relationship between local
      priority birth defect (BD) mortality in children under five years of age with
      demographic and economic variables representing megalopolization: urban
      localities,municipalities with larger populations and population density, and
      units and total gross output of agriculture, manufacturing and transportation.
      MATERIAL AND METHODS: Thematic maps were produced in the form of polygons and
      point to their juxtaposition and analysis of spatial correspondence. RESULTS:
      Priority municipality concentrations: 98.6% of the localities of 50,000 to
      99,999, 100% of the cities of 100,000 inhabitants or more; 84.3% of the total
      population; the activity and productivity of agricultural (62.7 and 82.2%),
      manufacturing (83.4 and 96.9%) and of transport (92.2 and 96.8%). CONCLUSIONS:
      Priority municipalities concur with those where the processes of urbanization and
      megalopolization have a more intense effect. There is scientific evidence in the
      medical literature on the relationship between megalopolization,pollution, and
      BD. It is proposed that more should be found out about this relationship in
      Mexico.

PMID- 21743589
TI  - [Factors associated to pulmonary tuberculosis in patients with diabetes mellitus
      from Veracruz, Mexico].
AB  - In Mexico, 20% of cases of tuberculosis (TB) are associated with diabetes
      mellitus (DM). However, the behavior of the factors related to this comorbidity
      is unknown, so the aim of this study was to estimate the risk factors and outcome
      for TB-DM in a population from the state of Veracruz, Mexico. We developed a
      double-design study: cases and controls for the estimation of risk factors, and a
      retrospective cohort for the outcome factors. The populations surveyed were 67
      patients with the comorbidity TB-DB and 109 with TB. The risk factors for
      tuberculosis in the diabetic population studied were: age >= 35 with an OR of 2.5
      (95% CI: 1.4-4.3) and IMC >= 25 with an OR of 8.5 (95% CI: 3.1-23.3). According
      to the outcome variables, the patients with TB-DM showed an increased risk of 2.8
      (95% CI: 2.2-3.4) for the development of drug resistance against tuberculosis. In
      conclusion, age and overweight are important risk factors, and drug resistance is
      an important outcome factor for the binomial TB-DM in the population from
      Veracruz. This information will have important effects on the development of
      surveillance programs against TB, with emphasis on the characteristics of the
      diabetic population.

PMID- 21743590
TI  - [Multicenter international registry to evaluate the clinical practice delivered
      to patients with type 2 diabetes mellitus: a sub-analysis of the experience in
      Mexico].
AB  - BACKGROUND: There is a lack of information on the characteristics of the medical
      attention delivered to Mexican patients with type 2 diabetes (T2D). Our aim was
      to describe the current state on the medical management of T2D in Mexico.
      METHODS: Among 17,232 patients included in the International Diabetes Management
      Practices Study (IDMPS), 2,620 (15%) corresponded to Mexico. Information
      regarding clinical, demographics and management characteristics, as well as the
      impact of T2D in the patient is clinical and social condition was registered. The
      metabolic control and achievement of therapeutic goals were also analyzed.
      RESULTS: Diagnosis of T2D was performed by the general practitioner in 76% of
      cases. Only about a quarter of the cohort had a blood pressure goal of < 130/80
      mmHg, although 97% had anti-hypertensive treatment. Management of T2D was with
      diet and exercise exclusively in 5%, with oral glucose-lowering drugs (OGLD) in
      66% (alone or combined), with OGLD and insulin in 18%, and with insulin alone in
      11%. Only 31% of patients reached the goal of HbA1c < 7. Self-monitoring was
      practiced in 50% of patients and 26% received education on diabetes. The managing
      physician is personal impression about the quality of the metabolic control was
      not in accordance with HbA1c. Eight percent of patients had work absences in the
      last 3 months due to complications of T2D (mean of 15 days lost). CONCLUSIONS: In
      Mexico, quality of metabolic control of T2D patients could have important
      deficiencies. The personal impression of the physician on the patient is
      metabolic control is not consistent with objective data.

PMID- 21743591
TI  - [Teaching performance assessment in Public Health employing three different
      strategies].
AB  - INTRODUCTION: The educational system depends upon the quality and performance of
      their faculty and should therefore be process of continuous improvement.
      OBJECTIVE: To assess the teaching performance of the Public Health professors, at
      the Faculty of Medicine, UNAM through three strategies. METHODS: Justification
      study. The evaluation was conducted under a mediational model through three
      strategies: students' opinion assessment, self-assessment and students' academic
      achievement. We applied descriptive statistics, Student t test, ANOVA and Pearson
      correlation. RESULTS: Twenty professors were evaluated from the Public Health
      department, representing 57% of all them who teach the subject. The professor's
      performance was highly valued self-assessment compared with assessment of student
      opinion, was confirmed by statistical analysis the difference was significant.
      The difference amongst the three evaluation strategies became more evident
      between self-assessment and the scores obtained by students in their academic
      achievement. CONCLUSIONS: The integration of these three strategies offers a more
      complete view of the teacher's performance quality. Academic achievement appears
      to be a more objective strategy for teaching performance assessment than
      students' opinion and self-assessment.

PMID- 21743592
TI  - [Physician's retirement. Introduction].
AB  - Retirement is an important issue in professional life for physicians.
      Nevertheless, studies on this particular situation are scarce. In this symposium
      several aspects on medical retirement are discussed, including its planning,
      impact on family dynamics, psychological aspects, the medical-surgical
      retirement, and malpractice as a result of age.

PMID- 21743593
TI  - [Planning the medical retirement for a happy old age].
AB  - There is little written information on how to plan the retirement from clinical
      activities in order to achieve happiness in the old age. There are different
      specialists with expertise, programs and routines designed to prevent, diagnose
      and treat different conditions typical of each of the cycles of life of human
      beings. The question is at what stage of life would it be appropriate to initiate
      the project and process of medical retirement?, as it should include prevention,
      routine, and a plan to slow down aging in order to arrive to old age with
      physical, mental and economical happiness. The intention of this paper is to
      propose a medical retirement plan to achieve happiness in the old age. The
      factors that determine aging are: genetics, the environment, and the character
      and will of the individual. Therefore the medical retirement plan to achieve
      happiness in old age should include the concepts of physical, mental and economic
      well being. Up to the extent that we maintain a physical, mental, and economic
      autonomy and fulfill the established retirement plan, we will succeed in delaying
      the onset of old age. We conclude that it is necessary to accept retirement and
      to plan ahead of it.

PMID- 21743594
TI  - [Physician's professional retirement. Family dynamics].
AB  - Human beings have a natural resistance to think about their old age, both
      personally and professionally. Governments have targeted efforts to successfully
      prolong the life of the population, situation which already is a social and
      economic problem. "Old is a person with physical, intellectual and emotional
      limitations, who has a reduced autonomy and welfare, as a result of the years
      lived". Not everyone ages at the same age; it will depend on health, habits,
      physical and intellectual activity, nutritional status, vices and attitude
      towards life. A physician may decide not to continue exercising medicine due to:
      health problems, because they do not want to, because they do not feel competent,
      because of the risk of having to deal with a complaint or a lawsuit, to have a
      new life project, or because they have no patients. The options available for a
      doctor at the time of retirement will depend on his/her age, health status, stage
      of the aging process: autonomy, dependency or old age; his/her physical and
      mental condition, professional development, economic situation and family
      environment. A doctor may remain independent, join another family or seek shelter
      in a retirement home.

PMID- 21743595
TI  - [Some psychological and emotional aspects of retirement in physicians: a first
      approach].
AB  - Retirement is a time of life marked by many social prejudices. However, links of
      retirement to depression do not have any scientific evidence. Retired physicians
      do not suffer more psychiatric disorders than those who continue working. It is
      worth pointing that retirement is part of the decline of life, so no wonder the
      fear and rejection generated. Retirement can also be seen as a rite of passage or
      transition. Rites of passage are events that mark the most important transitions
      in human life, such as birth, initiation into adulthood, marriage and death. In
      the medical profession, the end of high school, obtaining professional
      qualifications and completion of a specialty, mark the different stages of the
      physician's career. Most research that has studied the quality of life of retired
      physicians agrees that most doctors are satisfied with their new condition.
      Similarly, retired doctors who said they were dissatisfied with their new
      situation, this was not because they had left the profession, but because they
      were in poor health or had no family or economic stability. The present study
      aims at providing an overview of occupational retirement from the individual and
      ontological point of view.

PMID- 21743596
TI  - [Physician retirement from clinical practice: how and when].
AB  - In Mexico there is no legislation as to when a physician should retire from
      active practice as it is the case in other countries. The Mexican Social Security
      for instance, in its global working contract between the authorities and the
      employees, for the period 2009-2011 clearly stated that after 30 years of service
      for men and 27 for women the employee may retire but the physician can still work
      in another institution or in private practice for as long as he or she wants. In
      this article, the experience of distinguished Mexican surgeons who had written in
      the past in relation to this topic is acknowledged. A brief description of the
      retirement of physicians in Spain where the National Health System retire
      physicians from practice at age 65 and in some cases at age 70 is discussed. The
      author analyzes what happens in other activities of human mankind such as in the
      arts, painting, architecture, music, physics and philosophy, where there are
      plenty of outstanding examples of men and women doing their best work well over
      the age of 65. The names of some distinguished Mexican physicians past presidents
      of the Academy of Medicine are mentioned, all of them legends in the field of
      medicine who worked or continue to work many, many years after the age of 65. The
      author recognizes the process of accreditation and certification of medical
      specialists in Mexico that is carried out by the 47 specialty councils that have
      the recognition of the National Committee for Medical Specialties: CONACEM.
      Finally he offers his personal thoughts about what a physician may do when he or
      she is thinking of retiring and urges them not to throw away their personal
      experiences of many years in medical practice but instead to utilize the social
      networks such as Twitter or Facebook in order to continue to provide their
      expertise to young physicians who may benefit greatly.

PMID- 21743597
TI  - [Malpractice and physician's age].
AB  - Quality of medical care is an essential component in the analysis of health
      systems, its institutions and the medical act. Physician's age has been
      identified as a determinant element of quality of care. However, there is little
      information on this respect. This paper presents an analysis of the relationship
      between physician's age and medical complaints submitted to the CONAMED. It was
      found that the higher incidence of malpractice occurs between 30-49 years of age.
      Within the group with the highest incidence are the events related to treatment,
      either medical or surgical and in particular in the fields of traumatology and
      orthopedics (21.4%), gynecology and obstetrics (17.9%), and general medicine
      (10.7%). We conclude that physician's age does not seem to relate directly with
      malpractice events.

PMID- 21743598
TI  - [Assessment of moisturizing creams available in Mexico].
AB  - There is a broad diversity of moisturizers for the treatment of dry skin;
      however, we do not know their real effectiveness. The objective here was to
      evaluate different products through their capacity to increase the epidermal
      hydration level (EHL) and to reduce the transepidermal water loss (TEWL).
      MATERIALS AND METHODS: We evaluated twenty moisturizers in sixteen individuals.
      The analysis was made on volar forearm and basal measurements were made for EHL
      and TWEL with the later application of 8 gm of each moisturizer on a 2 cm2 area.
      RESULTS: For the EHL we found significant differences among the products (p <
      0.0001), but only 35% (n = 7) of the moisturizers registered ascending levels of
      hydration in the course of measurements. The variance analysis for TEWL also was
      significant (p < 0.0001). CONCLUSIONS: In the short term only a few products
      induced a significant change in EHL. This study demonstrates the necessity to
      obtain objective information in order to avoid false publicity claims that may
      erroneously influence our prescription habits.

PMID- 21743599
TI  - [An elderly female with abdominal pain].
AB  - A case of a 78-year-old female who presented with clinical, ultrasonographic and
      laboratory findings typical of acute cholecystitis is presented. Diagnostic
      laparoscopy revealed a hemorrhagic infrahepatic mass and free blood within the
      peritoneal space; the procedure was then converted to an open one, which
      identified a 15 x 5 cm mass corresponding to a gallbladder volvulus. The final
      histopathologic study confirmed the diagnosis. A gallbladder volvulus should be
      suspected in elderly patients, particularly in those with a previous history of
      significant weight loss, who additionally present positive clinical and
      paraclinical data of acute cholecystitis. There are no still biochemical exams
      that may preoperatively identify patients at high risk for this infrequent
      abnormality.

PMID- 21743600
TI  - [The physicians from Aguascalientes during the Mexican Revolution].
AB  - The historical event known as the Mexican Revolution (1910-1917) took place at
      different locations in the country and many people participated in it, directly
      or indirectly. In this paper I describe the role that some physicians played in
      this struggle in the state of Aguascalientes, where the social structure was
      broken up so thunderously. But why specifically physicians? Because they formed
      an important local sphere of influence, both socially and politically, and had
      vision, actions and sometimes conflicting ideals, that were all at the mercy of
      the vortex of the revolutionary social struggle that after its partial or total
      end, favored and exalted some while damaged and eliminated others. These were the
      doctors in their role as citizens, politicians, and even revolutionaries, who
      contributed to the forging of modern Mexico, inside and outside of
      Aguascalientes. Their contributions deserve to be remembered by all; good or bad
      as you may judge them, they only were the product of their time and particular
      circumstances.

PMID- 21743602
TI  - [Translational research in the Faculty of Medicine of the National University of
      Mexico].

PMID- 21743603
TI  - Sound scattering from two concentric fluid spheres (L).
AB  - The solution to the problem of plane wave and point source scattering by two
      concentric fluid spheres is derived. The effect of differences in sound speed,
      density, and absorption coefficient is taken into account. The scattered field is
      then found in the limit as the outer sphere becomes an infinitely thin shell and
      compared to the solution for a single fluid sphere for verification. A simulation
      is then performed using the concentric fluid sphere solution as an approximation
      to the human head and compared to the solution of a single fluid sphere with the
      properties of either bone or water. The solutions were found to be similar
      outside of the spheres but differ significantly inside the spheres.

PMID- 21743604
TI  - Modulation of cross polarization in motionally averaged solids by Variable Angle
      Spinning NMR.
AB  - In systems where the dipolar couplings are partially averaged by molecular
      motion, cross-polarization is modulated by sample spinning. The cross-polariation
      efficiency in Variable Angle Spinning (VAS) and Switched Angle Spinning (SAS)
      experiments on mobile samples is therefore strongly dependent on the spinning
      angle. We describe simulations and experimental measurements of these effects
      over a range of spinning angles from 0 degrees  to 90 degrees .

PMID- 21743605
TI  - Towards more rational and responsible patient care.

PMID- 21743607
TI  - The practice of ect in India: ii. The practical administration of ect.
AB  - A questionnaire on ECT, tapping attitudes, opinions and usage, was mailed to all
      medical members of the Indian Psychiatric Society whose addresses were known; 263
      (28.8%) responded. This paper, the second in a series that presents the results
      of the survey, describes the practical administration of ECT. Specific issues
      discussed are the availability of a cardiopulmonary resuscitation kit, ECT
      premedication, the ECT device, certain aspects of ECT stimulation, the electrode
      placement during ECT, administration of multiple ECT during a single treatment
      session and monitoring of the seizure duration. It is concluded that, in many
      respects, the practical administration of ECT in India in suboptimal; further
      research is required in certain areas.

PMID- 21743606
TI  - Benzodiazepines in psychotic States.
AB  - Benzodiazepines are primarily used for the treatment of generalized anxiety
      disorder, insomnia and status epilepticus. These drugs can also be useful in
      hyperaroused states, catatonic stupor, manic episodes, and akathisia. This paper
      will review indications for their use in various psychotic conditions.

PMID- 21743608
TI  - Efficacy of meditation in generalized anxiety disorder.
AB  - A study was conducted to compare the efficacy of meditation with that of
      imipramine and chlordiazepoxide in the treatment of Generalized Anxiety Disorder.
      At the end of five weeks, meditation was found to be as effective as
      pharmacotherapy in controlling symptoms of anxiety. It was superior in altering
      trait anxiety (TMAS Scores). Meditation is an easy to learn and cost effective
      therapy. It has a distinct edge over pharmacotherapy in that it is does not have
      the associated problems of habit formation,-withdrawal effects, overdosage or
      other undesirable effects.

PMID- 21743609
TI  - Combating aggression in institutionalized childern with physical exercise and
      music.
AB  - The results of a short-term trial of combating aggression in 20 institutionalized
      children of both sexes in the age range of 10-14 years are presented in this
      paper. Vigorous physical exercise and learning vocal music were the two remedial
      therapies employed Results indicate that the experimental group significantly
      increased its Group Conformity Ratings after the treatment. As far as the
      direction of aggression is concerned, the experimental group significantly
      reduced its extra-punitive responses. On the reaction of frustration, the
      experimental group improved its ego-strength after the treatment. The results are
      indicative of a better level of adjustment by the experimental group as a result
      of the therapies.

PMID- 21743610
TI  - Understanding schizophrenia: a family psychoeducational approach.
AB  - Many research findings have shown that the presence of a schizophrenic patient in
      the family proves very stressful for each individual family member, as well as
      for the network of family relationships. This paper outlines the proceedings of
      an innovative one-day program in family psychoeducation. Program content and
      participant responses are described; the need for the organization of further
      such programs for the dissemination of information are highlighted.

PMID- 21743611
TI  - Prevalence of psychiatry morbidity in an urban community of pondicherry.
AB  - A cross-sectional study on psychiatric morbidity was conducted in an urban area
      of Pondicherry between October 1988 and July 1989. A sample of 225 families
      covering 1115 people of all ages was selected by simple random technique. The
      prevalence rate was 99.4 per 1000, the prevalence among children being 58.6 per
      1000. It was found that age, education, occupation and marital status had
      significant correlation with mental morbidity. Out of 90 cases detected among
      adults, psychosis formed 20%, neuroses 47% and alcohol dependence syndrome
      constituted 30%. Among children two conditions commonly identified were mental
      retardation and nocturnal enuresis.

PMID- 21743612
TI  - Psychological crisis and general practitioners.
AB  - A study was conducted to ascertain how often GPs encountered patients with
      psychological crisis and their means of tackling such cases. A questionnaire was
      administered to 47 GPs attending a training course on drug de-addiction
      orientation program. It was observed that failure in an examination (22.9%),
      break up of a love affair (16.8%) and the death of someone very close to the
      patient (14.9%) were among the common causes precipitating a crisis. Regarding
      the treatment techniques, reassurance, tranquilizers and referral to a
      psychiatric set-up were most commonly resorted to. 68.1% of the GPs were not at
      all satisfied with the treatment administered by them and 78.9% of them felt the
      need for further training in psychiatry. Implications of these findings are
      discussed.

PMID- 21743613
TI  - Short term training of medical officers in menal health.
AB  - As specialist services are insufficient to meet the needs of the people,
      especially in rural areas, the training of medical and paramedical health staff
      through short courses in psychiatry has been recommended in the National Mental
      Health Program. A two week orientation course in mental health has been
      recommended for general physicians, including those working at the dispensary
      level. This paper focuses on the experience of imparting such training to 91
      medical officers in a general hospital psychiatric unit.

PMID- 21743614
TI  - Psychosis not otherwise specified - change of diagnosis at five year follow -up.
AB  - A five-year follow-up study of 38 patients with 'psychosis not otherwise
      specified' revealed that diagnostic change occurred in 34.2% of the patients.
      15.8% of the patients developed schizophrenia and 18.4% developed affective
      disorders. The initial diagnosis was retained in 65.8% of the patients. The onset
      of the illness was acute in patients from rural background and this is
      statistically significant. 42% of the patients presented only catatonic signs, of
      which nearly 70% showed full recovery.

PMID- 21743615
TI  - Restrained psychiatric outpatients: necessity, justification or violation of
      human rights?
AB  - Seventy patients were brought restrained to a Psychiatric outpatient department
      over a three month period, with the commonest site of restraint being the wrist.
      They were compared with controls and it was found that restrained patients were
      more likely to be younger, belonging to a lower socioeconomic status, from a
      rural background and were more likely to be diagnosed as manic. The significance
      of these findings and their implications for the human rights of the mentally ill
      are discussed.

PMID- 21743616
TI  - Distress and job performance of industrial workers.
AB  - The present study aims at the investigation of the relationship between distress
      and job performance of industrial workers. The sample consisted of 500 workers of
      public and private sectors. CMI Health Questionnaire and Performance Appraisal
      Scale (PAS) were used to measure the level of distress and quality of performance
      at job, respectively. Results showed that physical, menial and overall distress
      correlated significantly and negatively with workers 'performance as appraised
      Furthermore, levels of physical and mental distresses could forecast effectively
      the job performance of industrial workers.

PMID- 21743617
TI  - Urinary incontinence in acute psychosis.
AB  - A prospective two year study of consecutive admissions (n=984) to a psychiatry
      ward revealed that the incidence of temporary urinary incontinence in psychiatric
      patients without delirium or dementia was 1.63% (n=l6). When compared with
      controls (n=64) the incontinent patients were more often psychotic, gave a
      history of childhood enuresis and a past history of temporary incontinence during
      psychosis. Compared with psychotic controls (n=26), incontinent patients (n=16)
      had been exposed to a greater variety of treatments and were hospitalized for
      longer periods.

PMID- 21743618
TI  - The genetics of affective disorder - a pedigree study.
AB  - A study on the genetics of effective disorder was carried out using pedigree
      methodology. Ike index case presented with features of bulimia which was
      diagnosed to be Bipolar affective disorder. The pedigree was analyzed for 4
      generations and included evaluation of 76 individuals, of whom the oldest was 103
      years of age. The evaluation was done clinically to demonstrate various concepts
      concerning affective syndromes, the presence and extent of gene borne influences
      and mode of inheritance. Data was compared with other genetic research studies
      and suggestions for further research arc made.

PMID- 21743619
TI  - Effect of lithium therapy on thyroid function: a retrospective study on Indian
      patients.
AB  - Thirty patients with Bipolar affective disorder who were on Lithium therapy for 6
      months to 24 months, were tested for any alteration in their thyroid function.
      Eight (26.67%) patients had elevated serum TSH level and four (13.33%) patients
      had decreased serum T(4) level than the normal range. Serum T(3), although
      showing a declining trend was found within the normal range in all the patients.

PMID- 21743620
TI  - Long - lasting lithium neurotoxicity in an adolesecent.
AB  - Acute lithium intoxication is well known. A case of long tasting lithium
      neurotoxicity in an adolescent male is reported, who showed signs of cerebellar
      as well as brain stem involvement. Persistent lithium neurotoxicity is discussed
      and the recommendation made that this condition be considered irreversible only
      if no substantial recovery occurs in the first six months.

PMID- 21743621
TI  - Paroxysmal kinesiogenic choreoathetosis: a frequently misdiagnosed movement
      disorder.
AB  - Paroxysmal kinesiogenic choreoathetosis is rare movement disorder, which is
      frequently misdiagnosed as an epileptic disorder partly because of a good
      response to anti-epileptic drugs (Phenytoin sodium). At times these patients are
      mistaken for a conversion reaction. One such case is described.

PMID- 21743622
TI  - Stevens-johnson syndrome in a schizophrenic patient treated with carbamazepine.
AB  - A female schizophrenic patient who developed Stevens Johnson syndrome following
      carbamazepine treatment is reported. This life threatening condition is discussed
      in context of other adverse effects of the drug, reportedly found to be higher in
      frequency in the psychiatric population.

PMID- 21743623
TI  - Jhin-jhini - a hysterical constagion?

PMID- 21743624
TI  - Hypochondriasis and illness behavior.

PMID- 21743625
TI  - Aspects of abnormal illness behavior.

PMID- 21743626
TI  - The nonspecific symptom screening method a replication study.
AB  - Methods have been developed to screen non psychotic disorders in general health
      clinics based only on non-specific and somatic symptoms. One such method
      developed in India was applied in a heterogenous group of patients in a different
      clinical setting. The validity of nonspecific symptom screening method for non
      psychotic illness was replicated in this study. This method of screening is
      recommended for routine use in screening for minor psychiatric morbidity in
      medical and surgical clinics.

PMID- 21743627
TI  - Sensation seeking scale: Indian adaptation.
AB  - Sensation seeking refers to a biologically based personality dimension defined as
      the need for varied, novel and complex sensations and experiences, and the
      willingness to take physical and social risks for the sake of such experiences.
      Although researched worldwide for nearly three decades now, there is to date no
      published Indian study utilizing the concept of sensation seeking. This paper
      describes adaptation of the Sensation Seeking Scale for the Indian population.
      After due modification of the scale, its reliability, internal consistency and
      discriminant validity were established Norms were developed for a defined segment
      of general population. This study may be seen as the beginning of research in
      India on the subject of sensation seeking.

PMID- 21743628
TI  - Substance use by child labourers.
AB  - The present study highlights substance use patterns of 300 child labourers from 6
      slums in Sural city and identifies the microsocial and macrosocial stressors
      which initiate and perpetuate their substance use. It was observed that 135 (45%)
      of the child labourers had used some substance with a mean of 1.5 substances used
      per child. Tobacco smoking was the most common form of substance abuse followed
      by tobacco chewing, snuff, cannabis and opium. This study highlights an urgent
      need for the containment of substance abuse by these vulnerable early initiators.

PMID- 21743629
TI  - Drug abuse in kashmir - experience from a psychiatric diseases hospital.
AB  - Socio-demographic variables of 189 out-patients with drug abuse who were
      registered at the Hospital for Psychiatric Diseases, Srinagar were studied. Most
      of the drug abusers were male, the majority (57.2%) being in the 26-35 age group.
      Cannabis was the commonest substance abused, followed by heroin. Cannabis abusers
      had the longest duration of drug use but the lowest rate of drug dependence
      (29.9%) and lowest rate of multiple drug abuse (6.1%), whereas heroin abusers had
      the highest rate tjdrug dependence (88.8%) and highest rate of multiple drug
      abuse (83.4%). More than 50% of drug abusers had impairment in health and psycho
      social status. Problems with relatives or acquaintances led to treatment contact
      in about 62% of patients. Other socio-demographic variables such as marital,
      educational or occupational status did not reveal any significant difference.

PMID- 21743630
TI  - A psychodemographic study of the patients of a deaddiction centre in madras.
AB  - Sixty patients who reported to a Deaddiction Centre were investigated with regard
      to their psychodemographic profile. 53.3% of them turned out to be exclusively
      alcohol abusers, 35% were abusers of alcohol concurrently with other substances
      and 11.7% were abusers of exclusively drugs. Those who consumed alcohol alone,
      commenced their intake at a mean age of 24.4 years and reported for treatment
      only at 39.2 years; this was in contrast to the mean age of 17.9 years at which
      alcohol use begin in those who took alcohol in combination with other substances.
      Further, abusers of drugs alone reported for treatment at an age of 24 years,
      which is quite similar to the age at which the abusers of alcohol concomitantly
      with other substances resorted for psychiatric help. Other than the withdrawal
      syndrome, the most frequently encountered psychotic condition was alcoholic
      hallucinosis.

PMID- 21743631
TI  - Psycho-educational group therapy for alcohol and drug dependence recovery.
AB  - A brief psychosocial intervention model for alcohol and drug dependence recovery
      has been evolved in the form of psycho-educational group therapy. The package
      comprises of eight sessions conducted thrice a week over a period of about three
      weeks following detoxification. It aims to equip the patients with information
      and knowledge relevant to the needs of recovery. The program covers topics such
      as craving and relapse, medical complications, treatment process and recovery,
      family, social and job problems and structuring free time. Apart from achieving
      abstinence, the objectives of the program include enhancing functioning in
      personal, social and professional spheres by developing healthy and intimate
      relationships and promoting alternate activities.

PMID- 21743632
TI  - Effect of seizure control on improvement of cognitive functions in epileptic
      patients.
AB  - A group of fifty epileptic patients were tested with neuropsychological tools for
      cognitive functions like memory, intelligence, visuomotor coordination, spatial
      perception and body schema perception. Patients were on carbamazepine and were
      tested after three months. Seizure improvement was shown to have different
      effects on different cognitive functions. Memory and intellectual deficits
      improved, while no difference was observed in visuomotor coordination, spatial
      and personal perception.

PMID- 21743633
TI  - Ect induced EEG seizure: validity of duration estimation by last spike.
AB  - The seizure EEG records of 25 depressives receiving ECT were 'blindly' rated by
      two trained raters using a uniform definition of seizure endpoint. The EEG
      seizure duration estimates were validated against five expected relationships.
      EEG seizure duration correlated with and was more than motor seizure duration,
      reduced over the course of ECTs, was consistent within subjects, and negatively
      varied with age. Within clinical constraints, the method of seizure duration
      estimation by the last spike is valid.

PMID- 21743634
TI  - Influence of high fat diet on steady state bioavailability of lithium carbonate
      in manic depressive patients - a preliminary report.
AB  - The effect of high fat food in the steady state bioavailability of lithium
      carbonate (900 or 1200mg daily, in divided doses) was studied in three patients
      of manic-depressive psychosis in a self-control cross-over design. Serial blood
      samples were collected by venepuncture until 8 hours following drug
      administration and lithium was assayed by flame photometry. The results indicated
      a reduction in the extent of bioavailability of lithium by the high fat food as
      compared to standard normal diet, in all the three patients studied Caution
      should be exercised in regard to lithium administration along with food rich in
      fat content.

PMID- 21743635
TI  - Br-16a does not interfere with alpha - 2 noradrenergic and dopamine postsynaptic
      receptor functioning.
AB  - BR-16A is a herbal preparation with several putative psychotropic effects. Recent
      work has suggested that it facilities certain aspects of cognition and that it
      ameliorates ECT-induced amnesia in animal models. The present study sought to
      assess whether it affects noradrenergic and dopaminergic functioning in the
      central nervous system. Adult male Sprague-Dawley rats received BR-16A (200mg/kg)
      or vehicle for one month. The animals were subsequently challenged with clonidine
      (100 mg/kg I.P.), apomorphine (2mg/kg I.P.), or saline in a factorial design, and
      motility of the animals was immediately thereafter assessed using a small open
      field. BR-16A neither attenuated clonidine induced alpha-2 noradrenergic receptor
      mediated hypomotility nor accentuated apomorphine-induced dopamine postsynaptic
      receptor-mediated hypermotility, suggesting that it does not interfere with alpha
      2 noradrenergic and dopamine postsynaptic receptor functioning.

PMID- 21743636
TI  - Concentrations of homovanillic Acid and gonadal hormones in the serum of male
      schizophrenic patients.
AB  - The concentrations of serum homovanillic acid (HVA), luteinizing liormone (LH),
      follicle-stimulating hormone (FSH) and testosterone (T) were examined in 20 male
      schizophrenic patients not taking neuroleptic drugs, 44 treated with neuroleptic
      drugs, and 15 male healthy control subjects. Kurskal-Wallis analysis of variance
      showed no significant difference among the three groups in serum HVA, FSH, LH or
      testosterone although high concentrations were found in tlte patients not taking
      neuroleptic drugs. There was a significant positive correlation between serum HVA
      and FSH in the patients not taking neuroleptics. The present results suggest that
      the change of gonadal hormones may be related to the pathogenesis of
      schizophrenia.

PMID- 21743637
TI  - Seizure following fluoxetine.
AB  - Fluaxetine has not been often implicated in the production of generalized tonic
      clonic seizures. A patient with Bipolar Affective disorder who developed
      convulsions after receiving a single dose offluoxetine is reported. The
      implications are briefly discussed.

PMID- 21743638
TI  - The agoraphobic alcoholic: report of two cases.
AB  - The association between agoraphobia and alcohol dependence has been frequently
      observed in Western literature, but reports from India are lacking. Two cases
      demonstrating such an association are described. In both of them, the agoraphobic
      symptoms followed alcohol dependence. The interaction between these two
      conditions may set up a vicious cycle, and failure to recognize this co-morbidity
      may result in treatment failure.

PMID- 21743639
TI  - Munchausen' syndrome and trihexyphenidyl dependence.
AB  - The authors describe a woman with Munchausen's syndrome who, during the course of
      illness, developed dependence on Trihexyphenidyl which besides being partially
      treated was used in establishing the stable linkage with a hospital and was also
      successfully utilized in the management of Munchausen's syndrome.

PMID- 21743640
TI  - Pan masala - a new substance of dependence.

PMID- 21743641
TI  - Challenges in general hospital psychiatry.

PMID- 21743642
TI  - Psychological and sociodemographic correlates of the irritable bowel syndrome.
AB  - Thirty patients with the Irritable Bowel Syndrome (IBS) were evaluated for
      personality profiles and psychiatric morbidity. In comparison with normal
      controls, these patients were more neurotic, showed more anxiety and had a higher
      incidence of neurotic depression, anxiety neurosis and alcoholism. IBS was found
      to be more common in young, urban males and sedentary workers.

PMID- 21743643
TI  - Personality profiles of coronary cases.
AB  - Fifty coronary heart disease cases along with an equal number of controls,
      matched in age and educational levels were studied using Middlesex Hospital
      Questionnaire, Somatic Inkblot Series I and Command Hospital Questionnaire. They
      were between 20 and 55 years of age. Obsession and somatic personality traits
      measured on SIS variables were found to be statistically significant in coronary
      cases compared to controls. However the subject belief in the philosophy of
      "Karma" when measured on command hospital questionnaire did not show any
      difference between the two groups.

PMID- 21743644
TI  - A study of somatization disorder in an industrial hospital.
AB  - A group of psychiatric outpatients who satisfied the DSM-IIIR criteria for
      Somatization Disorder (n=33) were compared with a group of other Somatisers
      (n=32). The results show that somatization disorder was found predominantly in
      females. Their mean age was 31 and they had a lower income and poor educational
      level, with more life events and stress in the family. The main symptoms were
      gastrointestinal, cardiopulmonary, pain and conversion followed by menstrual and
      sexual symptoms. They were more extroverted, neurotic and anxious depressed with
      significant basic neurotic traits. These results are discussed.

PMID- 21743645
TI  - Geriatric patients attending a general hospital psychiatry clinic.
AB  - 238 case records of all the patients aged sixty years and above who visited
      psychiatry departments of two general hospitals during a three year period were
      retrospectively analyzed. The mean age of sample was 67 years; 43.7% of patients
      had functional psychosis. 55.8% of the functional cases had paranoid features.
      43.28% of the sample had at least one associated physical illness, the majority
      of the patients had a caring spouse, were from joint or extended families and had
      some education and at least part time occupation.

PMID- 21743646
TI  - General hospital psychiatry: psychiatric certificates.
AB  - A retrospective analysis of 70 cases referred for certification revealed that
      they accounted for less then 1% of total cases. Criminal cases constituted 50%
      and the rest were service and civil cases. There was no psychiatric problem
      detectable in 10% of the cases; 7% were for travel concessions. All the
      certificates issued in service matters were in favor of employees.

PMID- 21743647
TI  - Suicide attempts by agricultural chemicals.
AB  - Forty three patients (42%) used agricultural chemicals as a method of suicide
      over nine and a half years (from Oct. 1981 to March 1991), and most cases were
      reported in June (agricultural activity) and December (year's end). The highest
      prevalence was inpatients in their fifties (34.9%). 58.1% of these patients who
      committed suicide were farmers or had no fixed occupation. Main precipitating
      factor was difficulties in interpersonal relationships (30.9%), and the largest
      number of patients (25.6%) were diagnosed as having manic-depressive psychosis,
      depressed type.

PMID- 21743648
TI  - Physical morbidity with unmodified ect - a decade of experience.
AB  - Recent recommendations for the routine use of modified ECT prompted an audit to
      be undertaken to determine the incidence of musculoskeletal complications
      occurring in patients who received ECT at our centre from 1980 to 1990. Of the
      13,597 treatments given, 98% were unmodified, due to the lack of availability of
      anesthetists. Musculoskeletal complications occurred in less than 1% of
      treatments and were of little clinical significance. However, modified ECT was
      associated with significantly greater frequency of potentially fatal
      complications such as cardiac arrest. The findings of this audit indicate that
      unmodified ECT administered by a trained team does not result in significant
      musculoskeletal morbidity and may be preferable to modified ECT in the absence of
      trained anaesthetic personnel. The decision to routinely recommend modified ECT
      in developing countries should await scientific debate with due consideration of
      the complications, resources, ethics, practicality and cost as well as the
      consequences of such a recommendation on clinical practice.

PMID- 21743649
TI  - Psychotherapy programme for psychiatry residents at nimhans - 1. A descriptive
      account.
AB  - A formal, mandatory psychotherapy training programme for psychiatry residents at
      NIMHANS was started in 1983. It has made qualitatively encouraging progress. It
      has also focussed on issues demanding attention in the years to come. This paper
      is a descriptive account of the programme.

PMID- 21743650
TI  - Delusional parasitosis of body orifices - a cultural variant?
AB  - Predominant or specific involvement of the eyes, ears, nostrils, mouth, anus and
      urethra (the body orifices) has not previously been reported in the literature on
      delusional parasitosis. Their involvement in the cases reported here is discussed
      in the context of the Hindu religio-cultural belief system which attaches special
      significance to these organs in the personal quest for physical, mental and
      spiritual purity. The involvement of the ears, in particular, appears to be
      influenced by native healing methods.

PMID- 21743651
TI  - Senior medical students' attitude towards psychiatry : relationship with career
      interest.
AB  - Using the Senior Medical Student Questionnaire, the attitudes towards psychiatry
      and the career interest in psychiatry of 146 final year medical students were
      obtained. The results indicated that, on the overall merits of the field of
      psychiatry and role definition and functioning of psychiatrists, students had a
      favorable opinion. Many students considered that career and personal rewards in
      psychiatry are limited. Analysis of the relationship between career interest and
      attitudes showed that on many items students with a greater career interest in
      psychiatry had more favorable opinions. However, there was evidence to suggest
      that students with greater career interest in psychiatry were equally concerned
      about the low career and social rewards in psychiatry.

PMID- 21743652
TI  - Delusional parasitosis in leprosy.
AB  - A patient with leprosy along with delusional parasitosis is describeeLNeuritic
      manifestations of leprosy appear to have a triggering effect in the development
      of delusions.

PMID- 21743653
TI  - Genital self mutilation.
AB  - A case of genital self mutilation in schizophrenia is described and its
      psychopathology discussed.

PMID- 21743654
TI  - Fluoxetine in trichotillomania - a therapeutic dilemma.
AB  - Trichotillomania is an impulse control disorder which has been reported to
      respond to fluoxetine. A patient thus treated who, however, developed drug
      induced alopecia is reported.

PMID- 21743655
TI  - Multiple personality: fallout of communal disharmony.
AB  - A young unmarried Muslim female presented with the secondary personality of a
      married Hindu woman following the Hindu - Muslim riots. It is proposed that
      multiple personality can occur as a reaction to insecurities generated by
      traumatic events.

PMID- 21743656
TI  - Behavioral management of hypochondriasis.
AB  - In general medical practice, hypochondriasis is present in 3 to 14 percent of
      patients. This condition is reported as being resistant to treatment. In this
      paper, behavioral intervention in an adult male with hypochondriasis is outlined
      The management involved progressive relaxation, behavioral counseling and
      bibliotherapy.

PMID- 21743657
TI  - Lest the remedy aggravate the malady.

PMID- 21743658
TI  - Ethics in psychiatry.

PMID- 21743659
TI  - Evaluation of short term training in mental health for multipurpose workers.
AB  - Training of multipurpose workers in mental health is an essential component in
      the implementation of the National Mental Health Program. This study examines the
      efficacy of a six day training program and the changes in knowledge, management
      skills and attitudes of multipurpose workers with regard to mental disorders.

PMID- 21743660
TI  - The perception and experience of health personnel about the integration of mental
      health in general health services.
AB  - The National Mental Health Program of India focuses on the integration of mental
      health in general health services. Using a structured questionnaire, 100 health
      personnel (40 Medical Officers and 60 Health Assistants) in the District Mental
      Health Program were interviewed regarding their perception and knowledge about
      the integration of mental health in general health services. Most personnel were
      found to be satisfied with their new role in carrying out mental health services
      and only a few felt that it was an extra burden. Suggestions were made by them
      about the free supply of drugs, short and long term training and active
      supervision and support by the higher authorities.

PMID- 21743661
TI  - Risk factors for tardive dyskinesia.
AB  - Three hundred and fifty three patients who had been on antipsychotics for three
      months or more were assessed using Simpson Tardive Dyskinesia Rating Scale. 40.2%
      of these patients, who merited a diagnosis of probable Tardive Dyskinesia (TD) by
      the Schooler and Kane criteria, were reassessed three months later and 25.5% of
      the total sample were found to have persistent TD. Age, total antipsychotic
      dosage and duration of antipsychotic exposure were found to be positively
      correlated with persistent TD.

PMID- 21743662
TI  - Plea of insanity as a defense in criminal cases: an update.
AB  - Mc'Naughten Rule is die commonest formulation for plea of insanity in most
      countries. Although assessment of the mental state at the time of offence is
      difficult, few instruments have been devised for this purpose. In the USA,
      efforts are being made to abolish the insanity defense and in the United Kingdom,
      amendments in the provisions of insanity defense have been proposed. The authors
      have stressed the need for some changes in the relevant sections of Indian Penal
      Code to increase the credibility of Psychiatric testimony in such cases.

PMID- 21743663
TI  - Multifocal leucoencephalopathy presenting as antidepressant induced mania.
AB  - A male patient presented with tricyclic induced hypomania after treatment for
      chronic depression. On follow up the patient deteriorated towards dementia with
      multifocal leucoencephalopathy. The possible role of brain lesions in the
      causation of affective syndromes and the neurobiological hypothesis of bipolar
      syndromes are discussed. The authors propose that chronic depression should be
      thoroughly investigated for a probable Axis III diagnosis.

PMID- 21743664
TI  - Secondary mania following stroke.
AB  - Stroke is rarely reported as one of the organic brain disorders which could give
      rise to secondary mania. This report describes a case of secondary mania
      following right fronto-parietal infarction.

PMID- 21743665
TI  - Mania following hypnotherapy.
AB  - Switches into mania have been observed in unipolar and bipolar depressed patients
      following physical treatments as well as cognitive therapy. Such a phenomenon has
      not been observed with hypnotherapy and its occurrence in a depressive patient is
      reported here and discussed.

PMID- 21743666
TI  - Koro in an industrial setting.
AB  - This case of classical koro in a 52 year old male describes three essential
      characteristics, i.e., acute exacerbation of chronic anxiety, fear of genital
      retraction and fear that the complete disappearance of the organ into the abdomen
      will result in death. Various etiological, developmental and personality factors
      in the genesis of anxiety have been discussed. The patient was treated with
      anxiolytics, antidepressants and dual sex therapy and was followed up for five
      years.

PMID- 21743667
TI  - Fluoxetine and vascular headaches.
AB  - Headaches are a common adverse effect of fluoxetine therapy. A patient who
      developed vascular headaches while being treated for depression is reported and
      possible mechanisms discussed.

PMID- 21743668
TI  - Learning from others' mistakes.

PMID- 21743669
TI  - Rehabilitation in psychiatry: an overview.

PMID- 21743670
TI  - Psychoimmunology and functional psychoses: the Indian scene.

PMID- 21743671
TI  - Level of anxiety and dissociation in patients with conversion and dissociative
      disorders.
AB  - State Trait Anxiety Inventory and Questionnaire of Experiences of Dissociation
      were administered to an unbiased sample of sixty patients, including twenty seven
      patients with dissociative disorder, twenty four with conversion disorder and
      nine with both these diagnoses, using DSM III criteria. The differences in
      anxiety scores and level of dissociation among the three diagnostic groups were
      not statistically significant. The finding that a substantial proportion (15%) of
      patients had both diagnoses and the lack of difference in levels of anxiety and
      dissociation in the three groups suggests that these two diagnoses are closely
      related.

PMID- 21743672
TI  - Electromyograph feedback: treatment outcome in anxiety neurosis.
AB  - Twenty two clients were assessed before and after ten sessions of Electromyograph
      [EMG] feedback assisted relaxation on both psychological and physiological
      measures. Results demonstrated significant decreases in the symptom scores and
      anxiety, as seen on the self-report measures. The clients were found to be
      significantly less anxious on the Hamilton's Anxiety Rating Scale. Though there
      was a significant reduction in resting EMG levels, there was no significant
      decrease in the GSR of the clients. Clients could acquire feedback control as
      well as self-control.

PMID- 21743673
TI  - The correlates of the syndrome of depression in schizophrenia.
AB  - A depressive syndrome as identified by subjectively volunteered dysphoria
      occurred in 17.4% of a group of 45 DSM III-R schizophrenics, studied initially in
      a medication free state. Among the 24 patients who could be followed up for six
      months, another 25% developed depressive symptoms while on treatment. Mild
      depressive syndromes occurred more frequently in older patients, in association
      with retained insiglu and lower negative symptoms scores. While depressive
      symptoms occurred both in the medicated and unmedicated state, depressed
      medicated schizophrenics differed from non-depressed medicated schizophrenics on
      variables of total medication dosage, presence of extrapyramidal symptoms and
      insight.

PMID- 21743674
TI  - Development of motivation scale - clinical validation with alcohol dependents.
AB  - This study focusses on the development of a comprehensive multi-dimensional scale
      for assessing motivation for change in the alcohol dependent population. After
      establishing face validity, the items evolved were administered to a normal
      sample of 600 male subjects in whom psychiatric illness was ruled out. The data
      thus obtained was subjected to factor analysis. Six factors were obtained which
      accounted for 55.2% of variance. These together formed a 80 item five point scale
      and norms were established on a sample of 600 normal subjects. Further clinical
      validation was established on 30 alcohol dependent subjects and 30 normals. The
      status of motivation was found to be inadequate in alcohol dependent individuals
      as compared to the normals. Split-half reliability was carried out and the tool
      was found to be highly reliable.

PMID- 21743675
TI  - Psychiatric complications of chloroquine.
AB  - Sixty patients with chloroquine induced psychiatric complications are reported in
      the present series. Psychosis was the most common complication followed by
      anxiety state and seizures. The maximum number of patients were between the ages
      of 6 and 10 years and females (70.0%) outnumbered the males (30.0%). Headache and
      sleeplessness were found to be more common amongpatients developing psychiatric
      complications of chloroquine. The symptoms disappeared within 2 to 21 days after
      the discontinuation of chloroquine.

PMID- 21743676
TI  - Diagnostic characteristics of child psychiatric service utilizers.
AB  - Sex, age and diagnostic characteristics of a consecutive series of first contact
      children seen over a period of one year at a psychiatric center was analyzed Most
      of (he referrals were for male adolescents. "No diagnosis on Axis I" was quite
      common, especially in the younger age group; most of them had mental retardation.
      "Hysteria " was uncommon, and this was the only category which was slightly more
      common in girls. Manic depressive psychosis was the most common disorder among
      adolescents.

PMID- 21743677
TI  - Electroconvulsive therapy in catatonia associated with pneumothorax.
AB  - Recent advances in the method of application and monitoring of Electroconvulsive
      therapy (ECT) has facilitated its use even in the presence of serious physical
      illness. This case report b of a patient in catatonic stupor who developed an
      acute respiratory crisis, and in whom the use of ECT led to quick recovery not
      only from the psychiatric state but also helped recovery from the medical
      illness. The report highlights the need to use ECT, if indicated, in the presence
      of serious medical illness without hesitation.

PMID- 21743678
TI  - Acute psychotic disorder and hypoglycemia.
AB  - A variable array of neuroglycopenic symptoms are frequently encountered in the
      hypoglycemic stage, but acute psychotic disorders are quite rare. A fifty five
      year old female presented with an acute psychosis following oral sulfonylurea
      induced hypoglycemia without preceding features of adrenomedullary stimulation.
      This case report suggests that an acute and transient psychotic disorder may be
      an important neuroglycopenic feature and its early recognition protects the
      patient from severe hypoglycemic brain damage in a state of hypoglycemia
      unawareness.

PMID- 21743680
TI  - Restraining psychiatric patients.

PMID- 21743679
TI  - Akhtar & jagawat reply.

PMID- 21743681
TI  - Dependence on gul: an indigenous compound containing tobacco.

PMID- 21743682
TI  - Tharyan et Al reply.

PMID- 21743683
TI  - Physical morbidity and unmodified ect.

PMID- 21743684
TI  - Where do we go from here?

PMID- 21743685
TI  - Cerebral blood flow and metabolism in anxiety and anxiety disorders.
AB  - Anxiety disorders are some of the commonest psychiatric disorders and anxiety
      commonly co-exists with other psychiatric conditions. Anxiety can also be a
      normal emotion. Thus, study of the neurobiological effects of anxiety is of
      considerable significance. In the normal brain, cerebral blood flow (CBF) and
      metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected
      to provide new insight into alterations in brain function in anxiety disorders
      and other psychiatric disorders. Possible associations between stress I anxiety I
      panic and cerebral ischemia I stroke give additional significance to the effects
      of anxiety on CBF. With the advent of non-invasive techniques, study of CBF/CMR
      in anxiety disorders became easier. A large numbers of research reports are
      available on the effects of stress, anxiety and panic on CBF/CMR in normals and
      anxiety disorder patients. This article reviews the available human research on
      this topic.

PMID- 21743686
TI  - Cannabis related psychiatric syndromes: a selective review.
AB  - Association between cannabis use and various psychiatric syndromes does exist,
      but their nature remains elusive. Cannabis intoxication, 'cannabis psychosis' and
      certain other conditions related with cannabis use like flashbacks and prolonged
      depersonalization are discussed in this paper. The controversial nature of the
      cannabis - schizophrenia link is noted, and various methodological issues in
      clinical cannabis research are highlighted.

PMID- 21743687
TI  - Codeine containing cough syrup addiction in assam and nagaland.
AB  - The drug abuse monitoring study of Regional Medical Research Center, Dibrugarh,
      reported 181 and 395 addicts from the states of Assam and Nagaland respectively
      in one year. Of these, 48 (26.5%) and 49(12.4%) cases were contributed by the
      primary abuse of codeine containing cough syrups. A11 addicts were males in their
      early twenties. Most of the addicts were unmarried and educated up to
      matriculation. The majority of addicts in Assam were Hindus (85.4%) and in
      Nagaland Christians (81.63%). Unemployment was predominant in both the groups.
      The mean age for the first use of codeine cough syrup was 17.44 years (Assam) and
      15.77 years (Nagaland). Nagaland had more chronic abusers. Addicts were used the
      oral route several times a day and friends were the main source of introduction.
      Mild forms of physical and psychiatric disorders were reported Easy over-the
      counter availability, lesser expenditure, milder withdrawals and ease of
      consumption without secrecy were some of the reasons for the emergence of this
      new form of addiction in Assam and Nagaland.

PMID- 21743688
TI  - A study of comorbidity in psychoactive substance dependence patients.
AB  - The study assessed the lifetime prevalence of comorbidity in forty three DSM III
      R opioid and alcohol dependent patients. A total lifetime prevalence rate of
      60.5% was found. The results are discussed axis wise and compared with previous
      relevant studies. There was no significant difference in comorbidity between the
      opioid and alcohol Dependent groups. Comorbidity on both Axis I and II were high,
      but there was no significant difference in the presence of Axis I disorders
      between patients with and without personality disorders. The paper also reports
      upon the temporal relationships amongst the co-occurring psychiatric disorders.

PMID- 21743689
TI  - Psychoactive substance use among medical students.
AB  - Using a standard epidemiological survey instrument for psychoactive drug use, 215
      medical students in three classes were studied. One third of all students
      reported non-medical drug use. The substances ever used were: betel nut 13%,
      smokeless tobacco 3%, cigarettes 12%, alcohol 12.5%, cannabis 0.9% and
      benzodiazepines 3.7%. Last month use was reported for four substances and daily
      use was reported for cigarettes only (3.2%). Cigarette and benzodiazepine use
      mostly began after entry to medical college. Men and final year students had a
      higher prevalence of drug use.

PMID- 21743690
TI  - Psychiatric morbidity in college students and illiterate youths.
AB  - The profile of psychiatric morbidity in university students in a general hospital
      psychiatric clinic was studied and compared with age matched illiterate youths.
      Students represented 5.1% of the clinic population and illiterate youths
      represented 3.1%. The majority of ill students were males, unmarried and from a
      rural area. In both groups 75% of cases sought medical help on their own, but 42%
      of students solicited psychiatric help directly, in contrast to 11% of illiterate
      youths. Students reported relatively high role specific stress factors. In
      contrast to results of student surveys and university health centers, we found an
      equal representation of psychoses and non-psychoses, a lower representation of
      problems of under achievement and no representation of alcohol or drug abuse.

PMID- 21743691
TI  - Transient release reflexes in catonic schizophrenia.
AB  - This case report describes the presence of grasp reflex and palmomental reflex as
      a state dependant phenomenon in a 23 year old patient with catatonic
      schizophrenia. A transitory disturbance of frontal lobe function is proposed as
      the probable mechanism. The need to study the release reflexes as an effort to
      delineate a neurological "sub group" of schizophrenia is suggested.

PMID- 21743693
TI  - Our problems: our solutions.

PMID- 21743692
TI  - Physical harbingers of relapse in schizophrenia.
AB  - This is a case report of a patient with schizophrenic disorder, followed up
      prospectively over a period of six years through four episodes of illness. Her
      experience of a focal physical symptom as a consistent prodromal feature of each
      relapse forms the focus of the report as such a clinical phenomenon has not been
      recorded before. The possible reason for such presentation and the value of
      identifying the prodromal symptoms in the control of relapse are discussed.

PMID- 21743694
TI  - Role of yoga in the treatment of neurotic disorders: current status and future
      directions.
AB  - A large number of studies have consistently demonstrated the potential of yoga,
      not only in the treatment of psychiatric and psychosomatic disorder but also in
      promoting positive physical and mental health. This paper reviews various studies
      on the treatment of neurosis with techniques derived from yoga. A few lacunae
      have been identified and possible directions for future research are outlined. It
      is hoped that research along these lines will develop a standardized method of
      yoga therapy which can be utilized and integrated within the existing methods of
      treatment of neurotic disorders.

PMID- 21743695
TI  - Violence in India: a psychological perspective.
AB  - Intraspecific violence is now established as a biological phenomenon intrinsic to
      living nature. Ethologists maintain that culturally moulded programs of
      aggression which can be released by certain environmental triggers exist in the
      nervous system among higher animals. Evidence also suggests that there co-exists
      a biological capacity for morality and empathy. A child by the age of two is
      endowed with the capacity to refrain from hurting another person purely by
      identifying himself with the other. This moral faculty is strengthened by
      parental training, appropriate role models and a nurturing society. In India
      today, the weakening of cultural values due to rapid social change and the
      inability of elders and leadership to present a clear set of values which tliey
      themselves live by has induced a sense of alienation, powerlessness and
      meaninglessness among the youth. This makes them extremely susceptible to
      programs of aggression, all the while weakening their empathic and moral
      inclinations. The paper attempts an in-depth psychological examinations of these
      issues and also other factors responsible for violence in India. Psychologically
      rooted strategies to tackle the problem of violence in India are also discussed.

PMID- 21743696
TI  - Psychiatric morbidity in patients with chronic abdominal pain.
AB  - Fifty cases of chronic non-specific abdominal pain were studied prospectively.
      All patients were subjected to a detailed clinical examination and investigations
      related to gastrointestinal system. A full psychiatric assessment was done with
      application of Goldberg's 60 item's General Health Questionnaire. Thirty four
      (68%) patients had psychiatric symptoms, of whom twenty six (52%) had a definite
      psychiatric illness while the remaining eight patients had organic illness.
      Sixteen patients (32%) had a pure organic illness. Dysthymic disorder constituted
      the main (22%) psychiatric illness.

PMID- 21743697
TI  - Do Indian researchers read Indian research?
AB  - It is the authors' experience that papers in the Indian Journal of Psychiatry
      (IJP) under-reference relevant research previously published in the journal. To
      empirically address this issue, four volumes of the IJP, from 1989 to 1992 (both
      years inclusive), were surveyed. It was found that of 292 articles examined, 133
      articles (45.5%) had neglected to cite relevant articles previously published in
      the IJP. The overall ratio of IJP reference included to IJP reference omitted was
      1:1. Surprisingly, four articles were found to have been published twice in the
      IJP without the duplicate publication having been noticed and recorded. These
      findings suggest a need for introspection at author, referee and editorial
      levels.

PMID- 21743698
TI  - Medical students' attitudes towards psychiatry: effect of a two week posting.
AB  - The attitudes towards psychiatry of thirty, fourth year medical students were
      studied before and after a two week clinical posting, using an attitudes
      questionnaire. The results indicated that a two week posting in the specialty was
      not sufficient to significantly influence students' attitudes in a positive
      direction. The implications of these findings for undergraduate psychiatric
      education are discussed.

PMID- 21743699
TI  - Effect of rehabilitation on the prevalence of psychiatric morbidity among leprosy
      patients.
AB  - A hundred patients with leprosy were studied; forty six patients were
      rehabilitated and staying in an ashram while the remaining fifty four were not
      rehabilitated and staying in slum areas. A11 the patients were administered
      Goldberg's General Health Questionnaire (GHQ) and those who scored more than 12
      on the GHQ were administered Indian Psychiatric Interview Schedule (IPIS). The
      diagnosis of psychiatric illness was made according to ICD-9. Psychiatric
      morbidity was present in 76% of patients, with a statistically significant
      difference between the non rehabilitated group (85%) and rehabilitated groups
      (68%). It was noted that even rehabilitated patients expressed very high
      psychiatric symptomatology. Neurotic depression was present in about 67% of non
      rehabilitated and 41% of rehabilitated patients. Anxiety neurosis was reported in
      approximately 18% of non rehabilitated and 24% of rehabilitated patients. No
      other psychiatric illness was found.

PMID- 21743700
TI  - Neurocysticercosis presenting as schizophrenia: a case report.
AB  - Psychiatric manifestations of neurocysticercosis presenting mainly as organic
      psychosis are well documented. A patient with neurocysticercosis who presented
      with a schizophrenia like functional psychiatric illness is hereby reported.

PMID- 21743701
TI  - Charles bonnet syndrome: two case reports.
AB  - Two patients diagnosed to have Charles Bonnet syndrome are presented. In one of
      these, the symptoms were self limiting while in the other, the patient refused
      carbamazepine therapy despite persistence of symptoms. Both were followed up
      regularly over the four years, and mental status examination and investigations
      done during this period were within normal limits. Both are currently fully
      functional in their respective professions.

PMID- 21743702
TI  - Hallgren'S syndrome: two case reports.
AB  - Two cases of Hallgren's syndrome presenting with retinitis pigmentosa, sensory
      neural hearing loss along with schizophrenia in one patient and major depression
      in the other, are reported along with a brief description of this rare syndrome.

PMID- 21743703
TI  - Munchausen'S syndrome by proxy: a case report.
AB  - A two years old male child was referred from the child health department with a
      two month history of recurrent bleeding per rectum. The child was seen in
      multiple consultations elsewhere and extensively investigated to rule out
      gastrointestinal as well as bleeding disorders. During psychiatric interview,
      mother reported that she induced the rectal bleeding by injuring the rectal
      mucosa using her finger tip.

PMID- 21743704
TI  - A capgras like state for inanimate objects: two case reports.
AB  - Delusional doubling of inanimate objects, resembling the Capgras delusion was
      encountered in two cases of preexisting psychoses. This uncommon clinical feature
      is described and discussed.

PMID- 21743705
TI  - Coping with the reluctance to face reality.

PMID- 21743706
TI  - Efficacy of lithium prophylaxis in bipolar affective disorder.
AB  - Forty four patients attending the affective disorder clink at J1PMER Hospital who
      were on prophylactic lithium for bipolar affective disorder were studied, Intra
      individual comparison for severity of illness was made between periods of similar
      duration with and without lithium prophylaxis. It was found that during lithium
      prophylaxis patients did significantly better on the following parameters: number
      of episodes of illness, duration of episodes, hospital admission, neuroleptic
      dosages and duration of antidepressant treatment. Of the 44 patients included in
      the study, 45% were good responders, 39% were partial responders and 16% were
      poor responders. Late age of onset was found to be a significant predictor of
      good response to lithium.

PMID- 21743707
TI  - Once-daily versus divided dosage lithium therapy in acute mania.
AB  - The aim of the study was to compare once-daily with divided dosage lithium
      treatment in acute mania. In 79 retrospectively studied subjects who met the
      DSMIII-R criteria for mania, 26 independent and dependent variables were
      analyzed. The two groups of patients (categorized according to dosage schedule)
      were broadly comparable with respect to demographic and clinical characteristics.
      The two groups also did not differ on the outcome measures of lithium efficacy
      and lithium adverse effects. It is concluded that single dose lithium therapy is
      clinically comparable with divided dose lithium therapy in acute mania. Possible
      advantages of switching over to once-daily lithium regimes are discussed.

PMID- 21743708
TI  - A study of recent life events and their role in the precipitation of mania.
AB  - The present study of fifty patients was aimed at determining the prevalence and
      nature of recent life events and their role in the precipitation of mania. The
      role of other factors like family history of psychiatric illness and personality
      temperament were also taken into account. The study showed that 54% of patients
      with manic episodes had life events in the preceding one month. The commonest
      type of life event perceived was a financial problem, large loan, marital and
      family conflicts and damage to property or crops. Perception of life events had a
      statistically significant relationship with family history of mental illness and
      educational status.

PMID- 21743709
TI  - The sensation - seeker who is also alienated: towards a new hypothesis for
      genesis of opiate addiction.
AB  - The aim of the study was to assess two psychological parameters, sensation
      seeking (SS) and alienation (AL), in a sample of thirty DSM-III diagnosed opiate
      dependence cases, and to compare them on these two parameters with two non-drug
      abusing control groups, one from the patients own peer groups and the other from
      the general population. The opiate dependent subjects were found to score higher
      both on SS and AL than those in the control groups. Further, there was a gradient
      of the degree of correlation between these two psychological variables amongst
      the three groups studied. The opiate dependent group showed the highest positive
      correlation. The general population control group showed the lowest degree of
      correlation, and the self-matched control group was intermediate.These findings
      are consonant with an "SS-AL combination" hypothesis for the genesis of opiate
      addiction. Briefly, the hypothesis states that a higher sensation-seeking need,
      coupled with an inability to meet this need through socially sanctioned channels,
      leads on to repeated experiences with drug taking behavior, thus fostering
      dependence. The present study provides preliminary data supporting this
      hypothesis.

PMID- 21743710
TI  - Buprenorphine withdrawal syndrome.
AB  - The increasing use of buprenorphine among drug dependent subjects demands
      systematic enquiry into the clinical profile of buprenorphine withdrawal. Six
      male buprenorphine dependent (parenteral) subjects were observed for opiate
      withdrawal over a two week period. The onset of withdrawal occurred 48 hours
      after the last dose, peaked around the third day and lasted up to ten days. The
      withdrawals were similar to morpliine type drugs and moderate in intensity.

PMID- 21743711
TI  - Eating disorders in India.
AB  - Data on the nature and extent of major eating disorders, anorexia nervosa and
      bulimia is lacking in non-white, native populations of the developing world,
      leaving a gap in understanding the determinants of these disorders. In a study on
      210 medical students examined by a two-stage survey method, 31 subjects were
      found to have distress relating to their eating habits and body size not
      amounting to criterion-based diagnosis of eating disorders. The characteristics
      of this eating distress syndrome are described in relation to the major eating
      disorders.

PMID- 21743712
TI  - Impact of medical school experiences on senior medical students' interest in
      psychiatry.
AB  - This is a questionnaire study analyzing the influence of various medical school
      experiences on 146 final year medical students' interest and respect for
      psychiatry. The results indicated that clinical postings, lectures, contact with
      psychiatric patients and psychiatry faculty had a positive influence on majority
      of students. Many students perceived non-psychiatric faculty and fellow students
      as critical of psychiatry. Students with greater career interest in psychiatry
      were more positively influenced by contact with patients, faculty and clinical
      postings. When compared to results reported from developed nations, medical
      school experiences had a similar influence on our students. However, it is
      doubtful whether our findings can be generalized to other medical schools in
      Indian and further studies form other medical schools are warranted.

PMID- 21743713
TI  - Catatonia incidence in acute psychiatric admissions.
AB  - Eighty six consecutively admitted unmedicated patients, with a current duration
      of illness of less than two years, who fulfilled ICD-10 criteria for mood
      disorder or schizophrenia were assessed for catatonic signs over a three week
      study period Thirty two of them could be rated as catatonic, most of them
      starting to exhibit the signs at the time of admission or a few days thereafter.
      While the percentage of manic patients showing catatonic signs was comparable to
      earlier studies, a significant proportion of patients belonging to the
      Schizophrenic and Acute and Transient Psychotic Disorder group also exhibited
      these signs. The reasons for obtaining such a high percentage of catatonias are
      discussed. It is contended that short lasting catatonic signs are a common
      feature of acute psychiatric admissions and are ignored when viewed within the
      framework of an affective or psychotic illness.

PMID- 21743714
TI  - Somatization disorder in hiv seronegative men - a report of three cases.
AB  - Psychiatric morbidity among individuals at high risk of acquiring HIV infection
      has been reported in the form of anxiety, phobias and panic. We report three
      cases of seronegative men indulging in high risk behavior who continued to
      manifest somatization disorder despite the knowledge of their serostatus.
      Possible reasons and implications for future work are discussed.

PMID- 21743715
TI  - Benzodiazepines for prominent auditory hallucinations: a report and hypothesis.
AB  - A case is reported of diazepam - induced amelioration of prominent auditory
      hallucinations experienced by a female paranoid schizophrenic. With the
      assumption that subvocal speech may be primary to such hallucinations, it is
      proposed that diazepam may have acted by exerting a relaxant effect on speech
      musculature. This is a hypothesis testable in future research.

PMID- 21743716
TI  - A responsibility that we should not shirk.

PMID- 21743717
TI  - Contemporary society, health care scenario and psychiatrist.

PMID- 21743718
TI  - The saga of the developmentally disabled through the eons.

PMID- 21743719
TI  - The etiologic patterns in microcephaly with mental retardation.
AB  - Microcephaly with mental retardation forms a distinct subgroup among mentally
      retarded individuals. The paucity of studies on the etiology of this condition in
      India made the investigators to study this population. It HTO aimed to study the
      demographic and clinical characteristics, and the etiologic pattern in children
      with microcepltaly and mental retardation The sample consisted of 82 children who
      were examined by detailed clinical assessment and a battery of investigations. A
      definite etiology could be found in 56% of children which have been grouped into
      prenatal embryonic, prenatal maternal/environmental, and birth and neonatal
      causes. Non-genetic causes were the most common. The prenatal etiology
      constituted nearly twice that of birth and neonatal causes. Majority of the
      etiologic factors were preventable. The role of socio-environmental factors has
      been discussed As a group, the neurological disorders were found to be the most
      commonly associated medical condition. Malnutrition, specially of severe degree,
      was significantly associated with this group compared to the general population.
      The study findings indicate that there is a significant place for prevention.

PMID- 21743720
TI  - Family burden among long term psychiatric patients.
AB  - Subjective and objective burdens of the carers of schizophrenic and bipolar
      affective disorder patients were assessed. Burden was found to be higher among
      the carers of schizophrenic, young, male, low income and unemployed patients.
      This study shows a more comprehensive way of assessing family burden with due
      emphasis on positive mental health and coping resources of the carers.

PMID- 21743721
TI  - Palmar dermatoglyphics in schizophrenia.
AB  - Palm prints of 55 male and 33 female schizophrenic patients from Assam Medical
      College, Dibrugarh were examined for a possible association between palmar
      dermatoglyphic characteristics and the disease. There was a marked difference
      between patients and normal controls with regard to palmar C line termination,
      axial triadic, number of ridges at the a-b inter digital area and the frequency
      of various palmar flexion creases.

PMID- 21743722
TI  - Prevalence of priority psychiatric disorders in a rural area in kerala.
AB  - The objective of the study was to determine the prevalence rate of priority
      psychiatric disorders in a rural area in Kerala and to find out the
      sociodemographic correlates of the morbidity. A door to door survey had been
      conducted by trained surveyors to identify individuals with priority psychiatric
      disorders. The detected cases were examined by a psychiatrist at their houses in
      the village itself, to confirm as to whether they were having any psychiatric
      disorder. Out of the 1094 households surveyed (having a population of five
      thousand two hundred and eighty four), seventy seven individuals were found to
      have priority psychiatric disorders giving a prevalence rate of 14.57 per
      thousand. Females in general showed increased mental morbidity. An increased
      prevalence rate has been observed among Scheduled Castes/Scheduled Tribes. An
      increased morbidity is noticed among the people belonging to the lower
      socioeconomic status.

PMID- 21743723
TI  - Pesistent parkinsonism and tardive dyskinesia.
AB  - Parkinsonism and tardive dyskinesia can coexist in patients taking antipsychotic
      drugs. Persistence of both parkinsonism and tardive dyskinesia during a two year
      follow up period after discontinuation of antipsychotic drugs is reported.
      Etiological significance of antipsychotic treatment is discussed.

PMID- 21743724
TI  - Computers in ect and paperless EEG monitoring.

PMID- 21743725
TI  - Unmodified ect: a note of caution.

PMID- 21743726
TI  - What is simple in simple schizophrenia?

PMID- 21743727
TI  - Tharyan et al's reply.

PMID- 21743728
TI  - Easing their burden is our responsibility as well.

PMID- 21743729
TI  - Comparison of the extent and pattern of family burden in affective disorders and
      schizophrenia.
AB  - This study sought to compare the extent and pattern of burden experienced by
      relatives of two different patient groups, one with affective disorders and the
      other with schizophrenia. Cross-sectional assessment of family burden using the
      Pai and Kapur's Interview Schedule was done in 78 patients with either bipolar
      disorder or recurrent major depression and 60 patients with schizophrenia
      diagnosed according to DSM-III. The inter-rater reliability of the interview
      schedule for burden was also undertaken prior to the assessment of burden in the
      main study sample. Doth groups were similar with regard to sociodemographic
      variables, duration of illness and dysfunction of patient except for lower mean
      age and greater number of single patients in schizophrenia group. The extent of
      both objective and subjective burden was significantly more in relatives of
      schizophrenics. The pattern of burden was, however, almost similar in both the
      groups. Burden was principally fell in the areas of family routine, family
      leisure, family interaction and finances. The emotional health of the family was
      relatively untouched and the impact on physical health of the caring relatives
      due to burden of care was almost negligible. Various sociodemographic and
      clinical variables related to burden as well as the implication of the findings
      of the study are discussed.

PMID- 21743730
TI  - Incidence of adverse reactions to commonly prescribed psychopharmacological
      agents during early phase of therapy.
AB  - Five hundred and ninety two patients attending a psychiatric department as
      outpatients or as inpatient were included in this study. Details regarding age,
      sex, diagnosis and drugs prescribed were entered in a proforma. The information
      regarding drugs prescribed, dosage and the types of reactions were noted. All
      patients were followed up for a period of 3 to 4 weeks. Incidence of adverse
      reactions was calculated as percentage of the total number of prescriptions of
      the same group of drugs. The incidence of reactions to antipsychotic and
      antidepressants ranged from 35 to 46.9%. The incidence of reactions to
      haloperidol was higher than the reactions to other drugs. Antianxiety drugs were
      found to produce only minimal reactions. Two or more drugs prescribed together
      was associated with a higher incidence of reactions. Among the 193 patients who
      were reported to have reactions, 65.8% had extrapyramidal symptoms. The frequency
      of these reactions were highest with antipsychotic drugs haloperidol,
      chlorpromazine, trifluoperazine and thioridazine in that order. Dystonic
      reactions were reported within one to two days after the initiation of therapy in
      a large group of patients. Anticholinergic side effects were associated with
      prescription of tricyclic antidepressants andphenothiazines. Drowsiness,
      giddiness and postural hypotension were the other reactions associated with
      tricyclics.

PMID- 21743731
TI  - Social support and psychosocial dysfunction in depression.
AB  - Influence of social support on psychosocial dysfunction was studied in fifty
      newly diagnosed patients with major depression, using Social Support Scale (SSS)
      and Dysfunctional Analysis Questionnaire (DAQ) to measure social support and
      psychosocial dysfunction respectively. Total score on SSS did not affect the
      dysfunction. A positive relationship was observed between items of SSS relating
      to care, concern and expectations from others and negative relationship observed
      between SSS items referring to socialization and dysfunction in social and
      familial areas. The relationship of social support and psychosocial dysfunction
      appears quite complex with certain elements of social support having a healthy
      and others having an unhealthy relationship. Since measurement of social support
      itself is accompanied by a number of methodological problems such as distorted
      perceptions of psychiatric patients about social support, this makes the
      relationship more complex.

PMID- 21743732
TI  - Gender differnces in symptoms and course of schizophrenia.
AB  - This paper deals with gender differences in symptom pattern, course and
      (Usability in a cohort of 76 patients who were completely and prospectively
      followed up for a period often years. Both at inclusion and follow up, males had
      more of nuclear syndrome, but largely the differences were not statistically
      significant. Disability was more in the males, especially in the area of
      occupational functioning. The paper discusses gender based research in the Indian
      context.

PMID- 21743733
TI  - The relationship of insight to psychopathology in schizophrenia: a cross
      sectional study.
AB  - Insight plays an important role in the management of Schizophrenia. The study was
      undertaken to assess the cross-sectional relationship of clinical variables and
      psychopathology to insight, using the BPRS and the Insight Schedule. The study
      sample consisted of 59ICD-10 Schizophrenics with a mean duration of illness of
      41.88 months. Insight was found to have significant positive association with
      number of previous episodes of illness and treatment taken in the past. The
      correlation matrix of BPRS total score with Insight Schedule item scores revealed
      non significant negative correlations. On multiple regression analysis,
      psychopathology was found to explain significantly about a third of the
      variability in insight, thus demonstrating only partial dependence of insight on
      psychopathology. Construct analysis of the Insight Schedule was undertaken in
      parallel to the main study and revealed a component structure similar to that
      espoused by its author, ensuring comparability between the present and previous
      studies.

PMID- 21743734
TI  - Carbamazepine in interictal hyperreligiosity: three case reports.
AB  - Three patients with manifestations of hyperreligiosity during the post ictal
      period are presented- The compute clearance of these manifestations on
      carbamazepine monotherapy is highlighted.

PMID- 21743735
TI  - Issues in the use of manintenance electroconvulsive therapy.
AB  - This case report on the use of Maintenance Electroconvulsive Therapy (ECT-M)
      presents certain observations and raises some issues in the use of the method.
      The report offers wider indication for ECT-M, including schizophrenia and bipolar
      disorders and younger patients. It raises the issues that die duration of use of
      ECT-M can be short rather than indefinite and that in the post ECT-M period, drug
      maintenance using the same drugs which were ineffective pre-ECT-M can be used
      effectively. The report presents those observations for further systematic study.
      The cost benefit advantage of the method and its relevance to the need for more
      frequent use in developing countries is illustrated.

PMID- 21743736
TI  - Mania following typhoid: a case report.
AB  - Mania following or associated with medical and pharmacological conditions is well
      known. However there are not too many reports of mania following typhoid fever.
      This paper describes a mania syndrome following successfully treated typhoid
      fever in a young male without any past or family history of psychiatric illness
      or associated psychosocial stressors.

PMID- 21743737
TI  - Abuse of monoamine oxidase inhibitors.
AB  - Abuse of monoamine oxidase inhibitors is not common but there are a few cases of
      addiction in the literature. Most of these patients had an additional diagnosis,
      either history of past drug abuse or personality disorder and MAOI withdrawal
      symptoms have been reported. We encountered three patients who received MAOI
      under psychiatric care. They were all self medicated by increasing the doses on
      their own, experienced euphoria and visited various physicians to obtain MAOI
      prescriptions and manifested toxic states. One of our patients had a normal,
      another a schizoid and the third, an addictive personality. Two were addicted in
      the past to amphetamine. Therefore, it is important not to prescribe MAOI's to
      patients who have a history of amphetamine and other addictions.

PMID- 21743738
TI  - Behavior therapy for transsexualism.
AB  - Transsexualism is a rare disorder, and there is little literature available on
      its treatment. A case is presented of transsexualism with homosexual orientation
      in a 24 year old male. Since the disorder appeared to have behavioral
      antecedents, it was treated with a behavior therapy package comprising
      relaxation, aversion therapy with aversion relief, modelling, hypnosis, orgasmic
      reconditioning, behavioral counselling and sex education. Therapy resulted in
      normalization of gender identity, but the homosexual orientation persisted.

PMID- 21743739
TI  - Organic gastrointestinal illness and the irritable bowel syndrome.

PMID- 21743740
TI  - Need of the hour: an integration of the brain and the mind.

PMID- 21743741
TI  - J. Krishnamurti'S teachings - relevance to mental health.
AB  - The technique of J.Krishnamurti's communication marked by a dyadic style,
      'pariprasna', a sense of togetherness, absence of persuasion and
      authoritativeness could be incorporated into psychotherapeutic sessions. Self
      reliance and a genuine feeling of psychological oneness with others and to see
      things 'as they are' are discussed. The need for desirelessness to avoid
      conflicts and psychologically dying moment to moment to overcome fears e.g. of
      death and resolving chronic resentment is explained. A new way of ending sorrow
      has been pointed out. Krishnamurti's ideas on meditation have been dealt with
      briefly. Many of these concepts could be assimilated into psychiatric practice
      and towards promotion of mental health. Krishnamurti's call for a 'total
      transformation' of instant nature within the individual's psyche to effect a
      societal change is highlighted. Finally, a brief evaluation of Krishnamurti's
      contribution has been offered.

PMID- 21743742
TI  - Scarf social functioning index.
AB  - Several instruments measuring social functioning have been developed in the last
      four decades, as a result of the increasing interest in community care of the
      chronic mentally ill. SCARF Social Functioning Index (SSFI) was developed to meet
      the pressing need for an instrument which was easy to administer and which could
      be used by all mental health professionals. The SSFI comprises four main
      sections: self concern, occupational role, role in the family and other social
      roles. Each section has several subsections covering different areas of social
      functioning. Validity and reliability have been established for a group of
      normals, patients suffering from schizophrenia and from Hansen's disease.
      Internal consistencies of these factors were high Factor analysis derived four
      main factors, which included nearly all items of the SSFI. This paper reports on
      the development and standardization of the instrument.

PMID- 21743743
TI  - Psychological reactions to cataract surgery with intraocular lens implantation.
AB  - A prospective study of fifty patients who underwent cataract surgery with
      intraocular lens (IOL) implantation was undertaken. Factors aggravating and
      allaying pre-operative, intra-operative and post-operative anxiety were studied A
      good doctor-patient relations/lip, confidence in the ophthalmologist, and
      knowledge of successful surgery with IOL implantation in an acquaintance were the
      major anxiety relieving factors. The main anxiety provoking factors were concerns
      about the success of surgery and the requirement of laying immobile during
      surgery covered with surgical drapes. Detailed technical knowledge about the
      surgery was anxiety provoking and the majority of the patients did not desire it.

PMID- 21743744
TI  - An exploratory study of the motivation in suicide attempters.
AB  - The motivation of one hundred cases of suicide attempters was assessed clinically
      depending purely on their subjective reports. They were grouped into two, viz.,
      those who primarily wished for a change (here in after called WC) and those who
      unambiguously wished to die (hereinafter called WD). They were compared with
      regard to the details of the attempt, methods of attempt, psychiatric and
      sociodemographic profile. The WC group was observed to have taken less precaution
      against discovery of their attempt, had low lethality with regard to the method
      used and had more adjustment problems than psychiatric diseases. They clearly
      belonged to the low risk group. The WD group had all these findings in the
      contrary, which put them in the high risk category. This simple way of assessing
      suicide risk may be having a face validity in the sociocultural context of the
      present.

PMID- 21743745
TI  - Mental health delivery system in general hospitals attached to medical colleges.
AB  - The psychiatric patient care facilities and services of fifty seven general
      hospitals attached to medical colleges in India were studied based on data
      pertaining to 1988. The average bed strength was 25 beds while the average length
      of stay was 21 days. Functional psychotics formed 62% of the discharged patients.
      On the average, 2914 new psychiatric outpatients were registered per hospital and
      follow up attendance was 3.2 times more than the number of new cases. The
      implications of these findings and the method of obtaining average length of stay
      are discussed.

PMID- 21743746
TI  - Psychiatric morbidity and personality profile in divorce seeking couples.
AB  - To what extent psychiatric morbidity and personality factors contribute to
      marital disharmony and decision to divorce is still an unanswered question in
      Indian setting. This study was undertaken with aims to find out (1) the
      prevalence of psychiatric morbidity in persons seeking divorce; (2) the
      prevalence of psychiatric morbidity in persons who had good marital adjustment;
      (3) the nature of psychiatric morbidity observed in these subjects, and (4) the
      personality profile of these subjects. Fifty randomly selected divorce seeking
      couples (n=100) from the matrimonial court of Jaipur City and thirty couples with
      good marital adjustment (n=60) selected from the community were studied. Probable
      psychiatric cases identified by administering GHQ (Hindi version) were diagnosed
      according to ICD-10 and personality profile of all cases was studied by using 16
      PF. High psychiatric morbidity (50%) was found among divorce seeking couples in
      comparison to control group (13%). There was a high prevalence of neurone
      disorders (22%) and mood disorders (16%) in experimental group. Schizophrenia and
      related disorders (10%) and substance abuse disorder (2%) were seen only in the
      experimental group. Specific personality factors related to divorce seeking
      individuals and persons with stable marriage have been identified. The
      implications of this study are highlighted.

PMID- 21743747
TI  - Brain abscess presenting with catatonia.
AB  - A fifty year old man presented to a psychiatric unit with catatonia. He was later
      found to have a brain abscess in the left frontal region. Brain abscess has not
      been previously reported to be associated with catatonia.

PMID- 21743748
TI  - Yoga: some unanswered questions.

PMID- 21743749
TI  - Building Bridges Between Structural and Program Evaluation Approaches to
      Evaluating Policy.
AB  - This paper compares the structural approach to economic policy analysis with the
      program evaluation approach. It offers a third way to do policy analysis that
      combines the best features of both approaches. We illustrate the value of this
      alternative approach by making the implicit economics of LATE explicit, thereby
      extending the interpretability and range of policy questions that LATE can
      answer.

PMID- 21743750
TI  - Word and Person Effects on Decoding Accuracy: A New Look at an Old Question.
AB  - The purpose of this study was to extend the literature on decoding by bringing
      together two lines of research, namely person and word factors that affect
      decoding, using a crossed random-effects model. The sample was comprised of 196
      English-speaking grade 1 students. A researcher-developed pseudoword list was
      used as the primary outcome measure. Because grapheme-phoneme correspondence
      (GPC) knowledge was treated as person and word specific, we are able to conclude
      that it is neither necessary nor sufficient for a student to know all GPCs in a
      word before accurately decoding the word. And controlling for word-specific GPC
      knowledge, students with lower phonemic awareness and slower rapid naming skill
      have lower predicted probabilities of correct decoding than counterparts with
      superior skills. By assessing a person-by-word interaction, we found that
      students with lower phonemic awareness have more difficulty applying knowledge of
      complex vowel graphemes compared to complex consonant graphemes when decoding
      unfamiliar words. Implications of the methodology and results are discussed in
      light of future research.

PMID- 21743751
TI  - Nativity Status and Depressive Symptoms among Hispanic Young Adults: The Role of
      Stress Exposure.
AB  - OBJECTIVE: This article documents nativity differentials in depressive symptoms
      among Hispanics during their initial years of adulthood and explores how
      ethnicity, socio-demographic characteristics, and exposure to stressful life
      events and changes in social roles help to explain those differentials. METHODS:
      Data is drawn from a large-scale two-wave community study of stress, psychiatric
      well-being, and substance use disorders among young adults. Our analytic sample
      includes 553 Hispanic respondents and we employ multivariate regression
      techniques. RESULTS: Regardless of age at immigration, foreign-born women
      experience greater declines in depressive symptoms than native-born women during
      early adulthood. This advantage is explained by differences in perceptions of
      discrimination, family-based stress, and social role changes. The association
      between nativity and depressive symptoms is not conditioned by ethnicity, but
      ethnicity does condition the association between stressful events and depressive
      symptoms. CONCLUSIONS: The findings suggest that mental health treatment and
      prevention efforts should focus more heavily on stress exposure.

PMID- 21743752
TI  - Asymmetric palladium-catalyzed hydroarylation of styrenes and dienes.
AB  - Alkenes are desirable and highly versatile starting materials for organic
      transformations, and well-known substrates for palladium catalysis. Typically,
      these reactions result in the formation of a new alkene product via beta-hydride
      elimination. In contrast to this scenario, our laboratory has been involved in
      the development of alkene hydro- and difunctionalization reactions, where beta
      hydride elimination can be controlled. We report herein the development of an
      asymmetric palladium-catalyzed hydroarylation, which yields diarylmethine
      products in up to 75% ee. Interestingly, a linear free energy relationship is
      observed between the steric bulk of the ligand within a certain range and the
      enantiomeric excess of the reaction.

PMID- 21743753
TI  - A Longitudinal Study of Audiovisual Speech Perception by Children with Hearing
      Loss Who have Cochlear Implants.
AB  - The present study investigated the development of audiovisual speech perception
      skills in children who are prelingually deaf and received cochlear implants. We
      analyzed results from the Pediatric Speech Intelligibility (Jerger, Lewis,
      Hawkins, & Jerger, 1980) test of audiovisual spoken word and sentence recognition
      skills obtained from a large group of young children with cochlear implants
      enrolled in a longitudinal study, from pre-implantation to 3 years post
      implantation. The results revealed better performance under the audiovisual
      presentation condition compared with auditory-alone and visual-alone conditions.
      Performance in all three conditions improved over time following implantation.
      The results also revealed differential effects of early sensory and linguistic
      experience. Children from oral communication (OC) education backgrounds performed
      better overall than children from total communication (TC backgrounds. Finally,
      children in the early-implanted group performed better than children in the late
      implanted group in the auditory-alone presentation condition after 2 years of
      cochlear implant use, whereas children in the late-implanted group performed
      better than children in the early-implanted group in the visual-alone condition.
      The results of the present study suggest that measures of audiovisual speech
      perception may provide new methods to assess hearing, speech, and language
      development in young children with cochlear implants.

PMID- 21743754
TI  - Lead Speciation in the Dusts Emitted from Non-Ferrous Metallurgy Processes.
AB  - The paper presents results for the speciation analysis of lead in dusts derived
      from dedusting of technological gasses from metallurgical processes of non
      ferrous metals with different elementary content, made in accordance with two
      equal sequential extractions. Analytical procedure A provided possibilities for
      determination of fraction of Pb(2+), metallic lead and fraction containing mainly
      lead sulfides. The second procedure (procedure B) was sequential extraction in
      accordance with Tessier. The results obtained in accordance with procedure A
      indicate that, regardless of the dust origin, the dominant group of Pb compounds
      is composed of lead salts which are soluble under alkaline conditions or lead
      compounds that form plumbites in the reaction with NaOH.

PMID- 21743755
TI  - Railway transportation as a serious source of organic and inorganic pollution.
AB  - Polycyclic aromatic hydrocarbons and heavy metal (Pb, Cd, Cu, Zn, Hg, Fe, Co, Cr,
      Mo) contents were established in soil and plant samples collected in different
      areas of the railway junction Ilawa Glowna, Poland. Soil and plant samples were
      collected in four functional parts of the junction, i.e. the loading ramp, main
      track within platform area, rolling stock cleaning bay and the railway siding. It
      was found that all the investigated areas were strongly contaminated with
      polycyclic aromatic hydrocarbons (PAHs). The PAH contamination of the soil was
      the highest in the railway siding and in the platform area (59,508 and 49,670 MUg
      kg(-1), respectively). In the loading ramp and cleaning bay, the PAH
      concentration in soil was lower but still relatively very high (17,948 and 15,376
      MUg kg(-1), respectively). The contamination in the railway siding exceeded the
      average control level up to about 80 times. In the soil of all the investigated
      areas, four- and five-ring PAHs prevailed. The concentrations of PAHs were
      determined in four dominating species of plants found at the junction. The
      highest concentration was found in the aerial parts of Taraxacum officinale
      (22,492 MUg kg(-1)) growing in the cleaning bay. The comparison of the soil
      contamination with PAHs in the investigated railway junction showed a very
      significant increase of the PAHs level since 1995. It was found that the heavy
      metal contamination was also very high. Pb, Zn, Hg and Cd were established at the
      highest levels in the railway siding area, whereas Fe concentration was the
      highest in the platform area. A significant increase in mercury content was
      observed in the cleaning bay area. The investigations proved very significant
      increase of contamination with PAHs and similar heavy metals contamination in
      comparison with the concentration determined in the same areas 13 years ago.

PMID- 21743756
TI  - Sesame Allergy: Role of Specific IgE and Skin Prick Testing in Predicting Food
      Challenge Results.

PMID- 21743757
TI  - Assessing Jail Inmates' Proneness to Shame and Guilt: Feeling Bad About the
      Behavior or the Self?
AB  - This study of 550 jail inmates (379 male and 171 female) held on felony charges
      examines the reliability and validity of the Test of Self Conscious Affect 
      Socially Deviant Version (TOSCA-SD; Hanson & Tangney, 1996) as a measure of
      offenders' proneness to shame and proneness to guilt. Discriminant validity
      (e.g., vis-a-vis self-esteem, negative affect, social desirability/impression
      management) and convergent validity (e.g., vis-a-vis correlations with empathy,
      externalization of blame, anger, psychological symptoms, and substance use
      problems) was supported, paralleling results from community samples. Further,
      proneness to shame and guilt were differentially related to widely used risk
      measures from the field of criminal justice (e.g., criminal history, psychopathy,
      violence risk, antisocial personality). Guilt-proneness appears to be a
      protective factor, whereas there was no evidence that shame-proneness serves an
      inhibitory function. Subsequent analyses indicate these findings generalize quite
      well across gender and race. Implications for intervention and sentencing
      practices are discussed.

PMID- 21743758
TI  - Mechanisms of Bimaterial Attachment at the Interface of Tendon to Bone.
AB  - The material mismatch at the attachment of tendon to bone is amongst the most
      severe for any tensile connection in nature. Attaching dissimilar materials is a
      major challenge in engineering, and has proven to be a challenge in surgical
      practice as well. Here, we examine the material attachment schemes employed at
      this connection through the lens of solid mechanics. We identify four strategies
      to that the body adopts to achieve effective load transfer between tendon and
      bone: 1) a shallow attachment angle at the insertion of transitional tissue and
      bone, 2) shaping of gross tissue morphology of the transitional tissue, 3)
      interdigitation of bone with the transitional tissue, and 4) functional grading
      of transitional tissue between tendon and bone. We provide solutions to model
      problems that highlight the first two mechanisms, discuss the third qualitatively
      in the context of engineering practice, and provide a review of our earlier work
      on the fourth. We study these strategies both in terms of ways that biomimetic
      attachment might benefit engineering practice, and of ways that engineering
      experience might serve to improve surgical healing outcomes.

PMID- 21743759
TI  - Language context elicits native-like stop voicing in early bilinguals'
      productions in both L1 and L2.
AB  - The way that bilinguals produce phones in each of their languages provides a
      window into the nature of the bilingual phonological space. For stop consonants,
      if early sequential bilinguals, whose languages differ in voice onset time (VOT)
      distinctions, produce native-like VOTs in each of their languages, it would imply
      that they have developed separate first and second language phones, that is,
      language-specific phonetic realisations for stop-voicing distinctions. Given the
      ambiguous phonological status of Greek voiced stops, which has been debated but
      not investigated experimentally, Greek-English bilinguals can offer a unique
      perspective on this issue. We first recorded the speech of Greek and Australian
      English monolinguals to observe native VOTs in each language for /p, t, b, d/ in
      word-initial and word-medial (post-vocalic and post-nasal) positions. We then
      recorded fluent, early Greek-Australian-English bilinguals in either a Greek or
      English language context; all communication occurred in only one language. The
      bilinguals in the Greek context were indistinguishable from the Greek
      monolinguals, whereas the bilinguals in the English context matched the VOTs of
      the Australian-English monolinguals in initial position, but showed some modest
      differences from them in the phonetically more complex medial positions. We
      interpret these results as evidence that bilingual speakers possess phonetic
      categories for voiced versus voiceless stops that are specific to each language,
      but are influenced by positional context differently in their second than in
      their first language.

PMID- 21743760
TI  - COMPUTER GRAPHICS IN SIMULATION OF CARDIOVASCULAR TRANSPORT PHENOMENA.
AB  - Simulation is a necessary tool if we are to understand better the complexities
      involved in cardiovascular transport. While some of the phenomena modeled can be
      described analytically, perusal of the equations alone often doesn't result in
      full appreciation of the model system. It therefore becomes pertinent to utilize
      computer graphics in order to enhance simulation of physiologic transport
      processes. Graphic representation not only facilitates interaction between the
      investigator and the simulation, it provides a juxtaposition of the model to the
      real system, as well as a simplification of relationships between various
      features of the model.Increased mathematical sophistication required in the
      investigation of cardiovascular transport phenomena often makes traditional
      graphic representation cumbersome. Therefore several different types of graphics
      have been utilized, including 2-, 3-, and 4-dimensional displays. The methods and
      algorithms for these displays have been generalized to make them easy to use over
      a broad spectrum of applications. In some cases we have generated motion pictures
      of sequential model solutions which have increased and accelerated model
      comprehension, as well as been valuable for teaching purposes.

PMID- 21743761
TI  - Energy and Timing Measurement with Time-Based Detector Readout for PET
      Applications: Principle and Validation with Discrete Circuit Components.
AB  - A new signal processing method for PET application has been developed, with
      discrete circuit components to measure energy and timing of a gamma interaction
      based solely on digital timing processing without using an amplitude-to-digital
      convertor (ADC) or a constant fraction discriminator (CFD). A single channel
      discrete component time-based readout (TBR) circuit was implemented in a PC
      board. Initial circuit functionality and performance evaluations have been
      conducted. Accuracy and linearity of signal amplitude measurement were excellent,
      as measured with test pulses. The measured timing accuracy from test pulses
      reached to less than 300 ps, a value limited mainly by the timing jitter of the
      prototype electronics circuit. Both suitable energy and coincidence timing
      resolutions (~18% and ~1.0 ns) have been achieved with 3 * 3 * 20 mm(3) LYSO
      scintillator and photomultiplier tube-based detectors. With its relatively simple
      circuit and low cost, TBR is expected to be a suitable front-end signal readout
      electronics for compact PET or other radiation detectors requiring the reading of
      a large number of detector channels and demanding high performance for energy and
      timing measurement.

PMID- 21743762
TI  - Social Capital, Information, and Socioeconomic Disparities in Math Coursework.
AB  - Analysis of the National Education Longitudinal Study revealed that
      socioeconomically advantaged students persist in high school math at higher rates
      than their disadvantaged peers, even when they have the same initial placements
      and skill levels. These disparities are larger among students with prior records
      of low academic status because students from more privileged backgrounds persist
      in math coursework even when their prior performance predicts they will not.
      Among students with low middle school math performance, those from
      socioeconomically disadvantaged families appear to benefit from having
      consultants for coursework decisions, so that they make up ground with their
      socioeconomically advantaged peers.

PMID- 21743763
TI  - Risk and Protective Effects of Sibling Relationships among African American
      Adolescents.
AB  - This study investigated associations between sibling relationships and adjustment
      among 179 African American adolescent siblings (controlling for family factors),
      and tested moderating effects of familism values and birth order. Two-level
      random intercept models revealed that familism values moderated sibling
      relationship-adjustment linkages, suggesting that youth who reported both strong
      familism values and harmonious sibling relationships showed the most positive
      outcomes. These effects were more consistent for older than for younger siblings.
      Findings highlight the role of cultural values and birth order in shaping sibling
      influence processes.

PMID- 21743765
TI  - A Compact Modular Teleoperated Robotic System for Laparoscopic Surgery.
AB  - Compared with traditional open surgery, minimally invasive surgical procedures
      reduce patient trauma and recovery time, but the dexterity of the surgeon in
      laparoscopic surgery is reduced owing to the small incisions, long instruments
      and limited indirect visibility of the operative site inside the patient. Robotic
      surgical systems, teleoperated by surgeons from a master control console with
      joystick-type manipulation interfaces, have been commercially developed yet their
      adoption into standard practice may be limited owing to their size, complexity,
      cost and time-consuming setup, maintenance and sterilization procedures. The goal
      of our research is to improve the effectiveness of robot-assisted surgery by
      developing much smaller, simpler, modular, teleoperated robotic manipulator
      systems for minimally invasive surgery.

PMID- 21743766
TI  - A Review of Hot Deck Imputation for Survey Non-response.
AB  - Hot deck imputation is a method for handling missing data in which each missing
      value is replaced with an observed response from a "similar" unit. Despite being
      used extensively in practice, the theory is not as well developed as that of
      other imputation methods. We have found that no consensus exists as to the best
      way to apply the hot deck and obtain inferences from the completed data set. Here
      we review different forms of the hot deck and existing research on its
      statistical properties. We describe applications of the hot deck currently in
      use, including the U.S. Census Bureau's hot deck for the Current Population
      Survey (CPS). We also provide an extended example of variations of the hot deck
      applied to the third National Health and Nutrition Examination Survey (NHANES
      III). Some potential areas for future research are highlighted.

PMID- 21743767
TI  - Maternal investment, sibling competition, and offspring survival with increasing
      litter size and parity in pigs (Sus scrofa).
AB  - The aim of this study was to examine the effects of litter size and parity on
      sibling competition, piglet survival, and weight gain. It was predicted that
      competition for teats would increase with increasing litter size, resulting in a
      higher mortality due to maternal infanticide (i.e., crushing) and starvation,
      thus keeping the number of surviving piglets constant. We predicted negative
      effects on weight gain with increasing litter size. Based on maternal investment
      theory, we also predicted that piglet mortality would be higher for litters born
      late in a sow's life and thus that the number of surviving piglets would be
      higher in early litters. As predicted, piglet mortality increased with increasing
      litter size both due to an increased proportion of crushed piglets, where most of
      them failed in the teat competition, and due to starvation caused by increased
      sibling competition, resulting in a constant number of survivors. Piglet weight
      at day 1 and growth until weaning also declined with increasing litter size. Sows
      in parity four had higher piglet mortality due to starvation, but the number of
      surviving piglets was not affected by parity. In conclusion, piglet mortality
      caused by maternal crushing of piglets, many of which had no teat success, and
      starvation caused by sibling competition, increased with increasing litter size
      for most sow parities. The constant number of surviving piglets at the time of
      weaning suggests that 10 to 11 piglets could be close to the upper limit that the
      domestic sow is capable of taking care of.

PMID- 21743768
TI  - Support for maternal manipulation of developmental nutrition in a facultatively
      eusocial bee, Megalopta genalis (Halictidae).
AB  - Developmental maternal effects are a potentially important source of phenotypic
      variation, but they can be difficult to distinguish from other environmental
      factors. This is an important distinction within the context of social evolution,
      because if variation in offspring helping behavior is due to maternal
      manipulation, social selection may act on maternal phenotypes, as well as those
      of offspring. Factors correlated with social castes have been linked to variation
      in developmental nutrition, which might provide opportunity for females to
      manipulate the social behavior of their offspring. Megalopta genalis is a mass
      provisioning facultatively eusocial sweat bee for which production of males and
      females in social and solitary nests is concurrent and asynchronous. Female
      offspring may become either gynes (reproductive dispersers) or workers (non
      reproductive helpers). We predicted that if maternal manipulation plays a role in
      M. genalis caste determination, investment in daughters should vary more than for
      sons. The mass and protein content of pollen stores provided to female offspring
      varied significantly more than those of males, but volume and sugar content did
      not. Sugar content varied more among female eggs in social nests than in solitary
      nests. Provisions were larger, with higher nutrient content, for female eggs and
      in social nests. Adult females and males show different patterns of allometry,
      and their investment ratio ranged from 1.23 to 1.69. Adult body weight varied
      more for females than males, possibly reflecting increased variation in maternal
      investment in female offspring. These differences are consistent with a role for
      maternal manipulation in the social plasticity observed in M. genalis.

PMID- 21743769
TI  - Prior residency advantage for Atlantic salmon in the wild: effects of habitat
      quality.
AB  - Prior residency advantages have been explained by an asymmetry between the
      'owner' and the 'intruder' in fighting ability (resource-holding potential) or
      motivation (value asymmetry (VA)). Here, we tested for the extent of prior
      residence effects in individually tagged Atlantic salmon juveniles being released
      in two bouts (4 days apart) during spring along a natural stream, and recaptured
      3 months later. A prior residency advantage was detected both in terms of body
      growth, energy density and male gonad size. As we controlled for effects of
      initial body size, which correlates with dominance, these findings are in
      accordance with the VA hypothesis. The growth advantage of first arrivals also
      increased with local shelter abundance in the stream, which can be expected if a
      higher resource value of the habitat results in a higher defence motivation. We
      also found a prior residence effect on spatial distribution, with the second
      arrivals within each release site being recaptured further downstream. No effect
      on apparent survival rates was found. The observed reduced growth and energy
      density may have fitness consequences for the second arrivals, both in terms of
      lower winter survival rates and later age at maturity. For mature male parr, both
      decreased body and gonad growth may give an additional disadvantage through
      reduced fertilization rates during breeding. These costs may help to explain the
      tendency for stationary behaviour of stream salmonids, as the potential benefits
      of moving into less crowded areas would be reduced by the risk of becoming an
      intruder. Prior residence effects may therefore have influenced the evolution of
      movement behaviour in these organisms.

PMID- 21743770
TI  - Menstrual Cycle and Facial Preferences Reconsidered.
AB  - Two previous articles reported that women prefer less feminized male faces during
      the fertile phase of their menstrual cycle, supposedly reflecting an evolved
      mating strategy whereby women choose mates of maximum genetic quality when
      conception is likely. The current article contends this theory rests on several
      questionable assumptions about human ancestral mating systems. A new empirical
      test also was conducted: 853 adults, primarily from North America, evaluated
      facial attractiveness of photos. The study included more complete evaluation of
      ovulatory status and a greater number (n = 258) of target women than past
      research. The results did not suggest any greater preference for masculine faces
      when fertilization was likely. The article concludes with general comments about
      evolutionary theorizing and interpersonal relationships.

PMID- 21743771
TI  - The Rhymes that the Reader Perused Confused the Meaning: Phonological Effects
      during On-line Sentence Comprehension.
AB  - Research on written language comprehension has generally assumed that the
      phonological properties of a word have little effect on sentence comprehension
      beyond the processes of word recognition. Two experiments investigated this
      assumption. Participants silently read relative clauses in which two pairs of
      words either did or did not have a high degree of phonological overlap.
      Participants were slower reading and less accurate comprehending the overlap
      sentences compared to the non-overlapping controls, even though sentences were
      matched for plausibility and differed by only two words across overlap
      conditions. A comparison across experiments showed that the overlap effects were
      larger in the more difficult object relative than in subject relative sentences.
      The reading patterns showed that phonological representations affect not only
      memory for recently encountered sentences but also the developing sentence
      interpretation during on-line processing. Implications for theories of sentence
      processing and memory are discussed.

PMID- 21743772
TI  - Examining the Psychometric Properties of the Family Accommodation Scale-Parent
      Report (FAS-PR).
AB  - Growing research has examined parental accommodation among the families of
      children with obsessive-compulsive disorder (OCD). However, these studies have
      utilized a parent-report (PR) version of a measure, the Family Accommodation
      Scale (FAS) that has never received proper psychometric validation. In turn,
      previously derived subscales have been developed via clinical rather than
      empirical evidence. This study aims to conduct a comprehensive psychometric
      analysis of the FAS-PR utilizing data collected from 96 youths with OCD.
      Exploratory factors analysis was conducted and revealed a 12-item scale yielding
      two separate, yet related subscales, Avoidance of Triggers (AT) and Involvement
      in Compulsions (IC). Subsequent analyses revealed good internal consistency and
      convergent and discriminant validity. These findings suggest that future research
      should seek to examine factors that may impact various facets to accommodation as
      well as the role these facets plays in predicting treatment outcome. Limitations
      are discussed.

PMID- 21743774
TI  - "It's a Dignity Thing": Nursing Home Care Workers' Use of Emotions.
AB  - This article examines how nursing home care workers use emotions to construct
      dignity at work. Previous scholarship has shown how the financial and
      organizational characteristics of nursing homes shape and constrain emotion work
      among staff. Using evidence gathered during 18 months of participant observation
      in two nursing homes and 65 interviews with staff, this article analyzes how,
      despite obstacles, nursing home care workers generated authentic emotional
      attachments to residents. Surprisingly, some staff members said they particularly
      appreciated working with residents difficult to control. They felt accomplished
      when such residents successfully transitioned from life at home to life in
      institutional care. Emotions created dignity for staff and induced compliance
      among residents. Emotions are not only generated by organizations and imposed on
      workers; staff themselves produced emotions-sometimes in ways consistent with
      organizational demands, and sometimes not-and they consistently found in their
      emotions a resource to manage the strains of their work lives.

PMID- 21743773
TI  - Genetics of sweet taste preferences.
AB  - Sweet taste is a powerful factor influencing food acceptance. There is
      considerable variation in sweet taste perception and preferences within and among
      species. Although learning and homeostatic mechanisms contribute to this
      variation in sweet taste, much of it is genetically determined. Recent studies
      have shown that variation in the T1R genes contributes to within- and between
      species differences in sweet taste. In addition, our ongoing studies using the
      mouse model demonstrate that a significant portion of variation in sweetener
      preferences depends on genes that are not involved in peripheral taste
      processing. These genes are likely involved in central mechanisms of sweet taste
      processing, reward and/or motivation. Genetic variation in sweet taste not only
      influences food choice and intake, but is also associated with proclivity to
      drink alcohol. Both peripheral and central mechanisms of sweet taste underlie
      correlation between sweet-liking and alcohol consumption in animal models and
      humans. All these data illustrate complex genetics of sweet taste preferences and
      its impact on human nutrition and health. Identification of genes responsible for
      within- and between-species variation in sweet taste can provide tools to better
      control food acceptance in humans and other animals.

PMID- 21743775
TI  - Energy Management of People in Organizations: A Review and Research Agenda.
AB  - Although energy is a concept that is implied in many motivational theories, is
      hardly ever explicitly mentioned or researched. The current article first relates
      theories and research findings that were thus far not explicitly related to
      energy. We describe theories such as flow, subjective well-being, engagement and
      burn-out, and make the link with energy more explicit. Also, we make a first link
      between personality characteristics and energy, and describe the role of
      leadership in unleashing followers' energy. Following, we identify how the topic
      of energy management can be profitably incorporated in research from a scientific
      as well as a practitioner viewpoint. Finally, we describe several interventions
      to enhance energy in individuals and organizations.

PMID- 21743776
TI  - The Relationship between Syntactic Development and Theory of Mind: Evidence from
      a Small-Population Study of a Developmental Language Disorder.

PMID- 21743777
TI  - Quasi-static Torsional Deformation Behavior of Porous Ti6Al4V alloy.
AB  - Laser processed Ti6Al4V alloy samples with total porosities of 0%, 10% and 20%
      have been subjected to torsional loading to determine mechanical properties and
      to understand the deformation behavior. The torsional yield strength and modulus
      of porous Ti alloy samples was found to be in the range of 185-332 MPa and 5.7-11
      GPa, respectively. With an increase in the porosity both the strength and the
      modulus decreased, and at 20% porosity the torsional modulus of Ti6Al4V alloy was
      found to be very close to that of human cortical bone. Further, the experiments
      revealed clear strain hardening and ductile deformation in all the samples, which
      suggests that the inherent brittleness associated solid-state sintered porous
      materials can be completely eliminated via laser processing for load bearing
      metal implant applications.

PMID- 21743778
TI  - Efficient, scalable asymmetric synthesis of an epoxy quinol via Noyori
      desymmetrization of a meso diketone.
AB  - Epoxy quinol 1a was prepared on a multi-gram scale by Noyori transfer
      hydrogenative desymmetrization of the readily available meso epoxy diketone 4.
      Although the intrinsic enantioselectivity for the desymmetrization was modest
      (82:18 er at 4% conversion), a highly enantiopure product (99.6:0.4 er) could be
      obtained in one operation in 44% yield via kinetic resolution of the minor
      enantiomer with long reaction times (48 h), or in 73% yield by combination with
      an enzymatic resolution of a 93:7 er mixture.

PMID- 21743779
TI  - Evolution of Zinc Oxide Nanostructures through Kinetics Control.
AB  - In-depth understanding of the kinetics of the vapor deposition process is
      substantial for advancing this capable bottom-up nanostructure synthesis approach
      into a versatile large-scale nanomanufacturing technology. In this paper, we
      report a systematic study of the vapor deposition kinetics of ZnO nanomaterials
      under controlled atmosphere and properly refined deposition conditions. The
      experiments clearly evidenced the self-catalyzed growth of ZnO NWs via the
      formation of ZnO nanoflowers. This result illustrated how ZnO morphologies were
      associated with the discrepancy between oxidation rate and condensation rate of
      Zn. The capability of switching the NW morphologies and possibly mechanisms was
      demonstrated by kinetically controlling the deposition system. The high Zn
      composition during the deposition resulted in strongly luminescent NWs, which can
      be used for optical imaging applications. This research discovered a fundamental
      kinetics that governs the mechanisms and morphology selection of nanostructures
      in a non-catalyst growth system.

PMID- 21743781
TI  - Is the parvocellular red nucleus involved in cerebellar motor learning?
AB  - The anatomical connections of the parvocellular red nucleus (RNp) have led to the
      suggestion that it might participate along with the cerebellum in modifying old
      and developing new programs for the control of complex, compound, coordinated
      movements of multiple body parts. RNp projects to and excites the inferior
      olivary nuclear neurons, which send climbing fibers to excite neurons in
      contralateral cerebellar cortex and nuclei. RNp receives excitatory inputs from
      ipsilateral cerebral cortex (onto distal dendrites) and from contralateral
      cerebellar nuclei (onto proximal dendrites). We here further develop a hypothesis
      as to mechanism, and offer preliminary evidence from RNp inactivation studies in
      awake, trained macaques during modification of their gaze-reach calibration while
      wearing wedge prism spectacles.

PMID- 21743780
TI  - THE MULTIFACETED ROLE OF T CELL-MEDIATED IMMUNITY IN PATHOGENESIS AND RESISTANCE
      TO MYCOPLASMA RESPIRATORY DISEASE.
AB  - Mycoplasma respiratory diseases have a significant impact on the economy, health
      and wildlife. The hallmark of these diseases is the persistence of the mycoplasma
      infections and chronic inflammatory responses associated with the airways. There
      is still much that needs to be understood about the immune mechanisms involved in
      mycoplasma disease and resistance from infection. It is clear that immune
      responses can contribute to the generation of inflammatory lesions in mycoplasma
      respiratory disease, as well as provide protection from infection and
      extrapulmonary dissemination of the organisms. The evolution of this lung disease
      is under the control innate immune mechanisms and the contrasting effects of
      different T cell populations. The mechanisms of immunity involved in mycoplasma
      diseases are multifaceted, and a fascinating story of its complexity is being
      uncovered. Research in mycoplasma respiratory diseases have underscored the idea
      that immunity along the respiratory tract against infectious agents is a dynamic
      process and involves a network of cellular and cytokine signals that determine
      the type of responses generated, and ultimately, the outcome of infection. The
      aim of this article is to present on overview of our work on mycoplasma disease
      and immunity, focusing on the interactions and regulation of T cell responses
      that influence disease pathogenesis. We will first provide an overview of immune
      mechanisms involved in controlling infection and participate in the generation of
      T cell responses, and the role of T cell populations in generating protection and
      contributing to lesion development will be discussed.

PMID- 21743782
TI  - Lentiviral Based Gene Transduction and Promoter Studies in Human Hematopoietic
      Stem Cells (hHSCs).
AB  - Human hematopoietic stem cells (hHSCs) have enormous potential for clinical use
      in cell-based therapies, especially as a gene delivery system. Moreover,
      lentiviral transduction in stem cells is very often associated with low
      transduction efficiency and low levels of foreign gene expression. Therefore, it
      is important to analyze vector and promoter systems that can generate robust
      foreign gene expression in these cells. In this study, we evaluated and compared
      the ability of different commercially available promoters to drive the expression
      of exogenous reporter genes in hHSCs and evaluated the effect of different doses
      of stem cell growth factors on the expression of transgenes. We used lentivirus
      based vector system carrying the following promoters: 1) Human cytomegalovirus
      (CMV) promoter, 2) Simian virus 40 (SV40) promoter, 3) mammalian Ubiquitin C
      (UBC) promoter and 4) cellular polypeptide chain elongation factor 1 alpha (EF1)
      promoter. EF1 and CMV promoters robustly drove the expression of green
      fluorescence protein (GFP) reporter gene, while SV40 and UBC promoters induced
      very low level of GFP expression. Lentivectors containing EF1 and CMV promoters
      showed high-level stable GFP expression in human cord blood stem cells for 6
      weeks period after post transduction. CD133+ hHSCs stimulated with higher
      concentration of growth factors exhibited enhancement of transduction rate. Cord
      blood derived CD133+ hHSCs could be effectively transduced with lentivectors
      under CMV or EF-1 promoters for the expression of foreign gene. 

PMID- 21743783
TI  - TRANSCRIPTIONAL AND PHOSPHO-PROTEOMIC SCREENS REVEAL STEM CELL ACTIVATION OF
      INSULIN-RESISTANCE AND TRANSFORMATION PATHWAYS FOLLOWING A SINGLE MINIMALLY TOXIC
      EPISODE OF ROS.
AB  - Elevated reactive oxidative species (ROS) are cytotoxic, and chronic elevated
      levels of ROS have been implicated in multiple diseases as well as cellular
      transformation and tumor progression. However, the potential for a transient and
      minimally toxic episode of ROS exposure, or a minimal threshold dose of ROS, to
      initiate disease or cellular transformation is unclear. We examined both
      transcriptional and phospho-proteomic responses of murine embryonic stem (ES)
      cells to a single brief exposure of minimally toxic hydrogen peroxide (H(2)O(2)).
      The cellular response was distinct from those induced by either an acute exposure
      to H(2)O(2) or the topoisomerase II poison etoposide. Analysis of tumorigenesis
      related transcripts revealed a significant up-regulation of oncogenes and down
      regulation of tumor suppressors. Analysis of the phospho-proteomic response
      demonstrated insulin-signaling induction, including insulin receptor Y972
      hypophosphorylation, similar to insulin-resistance mouse models and observed in
      diabetic patients. In addition, ES cells were more resistant to ROS than
      differentiated cells, and retained their transcriptional self-renewal signature,
      suggesting stem cells have a higher potential for ROS-mediated mutagenesis and
      proliferation in vivo. These results are a direct demonstration that even brief
      and non-toxic exposures to ROS may induce transduction of insulin resistance and
      transformation signaling in stem cells leading to diabetes and cancer.

PMID- 21743784
TI  - Free-space fluorescence tomography with adaptive sampling based on anatomical
      information from microCT.
AB  - Image reconstruction is one of the main challenges for fluorescence tomography.
      For in vivo experiments on small animals, in particular, the inhomogeneous
      optical properties and irregular surface of the animal make free-space image
      reconstruction challenging because of the difficulties in accurately modeling the
      forward problem and the finite dynamic range of the photodetector. These two
      factors are fundamentally limited by the currently available forward models and
      photonic technologies. Nonetheless, both limitations can be significantly eased
      using a signal processing approach. We have recently constructed a free-space
      panoramic fluorescence diffuse optical tomography system to take advantage of co
      registered microCT data acquired from the same animal. In this article, we
      present a data processing strategy that adaptively selects the optical sampling
      points in the raw 2-D fluorescent CCD images. Specifically, the general sampling
      area and sampling density are initially specified to create a set of potential
      sampling points sufficient to cover the region of interest. Based on 3-D
      anatomical information from the microCT and the fluorescent CCD images, data
      points are excluded from the set when they are located in an area where either
      the forward model is known to be problematic (e.g., large wrinkles on the skin)
      or where the signal is unreliable (e.g., saturated or low signal-to-noise ratio).
      Parallel Monte Carlo software was implemented to compute the sensitivity function
      for image reconstruction. Animal experiments were conducted on a mouse cadaver
      with an artificial fluorescent inclusion. Compared to our previous results using
      a finite element method, the newly developed parallel Monte Carlo software and
      the adaptive sampling strategy produced favorable reconstruction results.

PMID- 21743785
TI  - A Twin and Adoption Study of Reading Achievement: Exploration of Shared
      Environmental and Gene-Environment-Interaction Effects.
AB  - Existing behavior-genetic research implicates substantial influence of heredity
      and modest influence of shared environment on reading achievement and reading
      disability. Applying DeFries-Fulker analysis to a combined sample of twins and
      adoptees (N = 4,886, including 266 reading-disabled probands), the present study
      replicates prior findings of considerable heritability for both reading
      achievement and reading disability. A simple biometric model adequately described
      parent and offspring data (combined N = 9,430 parents and offspring) across
      differing types of families present in the sample Analyses yielded a high
      heritability estimate (around 0.70) and a negligible shared-environmentality
      estimate for both reading achievement and reading disability. No evidence of gene
      * environment interaction was found for parental reading ability and parental
      educational attainment, the two moderators analyzed.

PMID- 21743786
TI  - CLINICAL MANAGEMENT OF FAMILIES WITH HEREDITARY COLORECTAL CANCER SYNDROMES.
AB  - Hereditary colorectal cancer syndromes can be associated with a lifetime risk of
      CRC of >70% in the absence of specialized surveillance. Diagnosing a genetic
      predisposition to cancer allows clinicians to tailor cancer prevention strategies
      for patients and families at highest risk. Once a genetic syndrome has been
      identified in a family, communication with family members, timely implementation
      of screening tests and/or surgeries, and psychosocial support are all
      instrumental for effective cancer prevention.Molecular screening of tumors,
      computerized risk assessment models, and genetic testing can help clinicians
      identify individuals at risk for hereditary cancer syndromes. This review
      discusses some of the complexities involved in the diagnosis and management of
      families with hereditary CRC syndromes and provides strategies for coordinating
      clinical care.

PMID- 21743787
TI  - Genetic diagnosis in pediatric cardiomyopathy: clinical application and research
      perspectives.
AB  - There has been tremendous growth in the application of genetics to the clinical
      practice of pediatric cardiomyopathy. The identification of the genetic basis for
      cardiomyopathies is important for establishing a causal diagnosis, providing
      definitive identification of at risk family members, and providing cost-effective
      screening and surveillance. Additional research is needed to better understand
      the genetic heterogeneity of cardiomyopathy in children, the implications of
      specific genotypes, the best approach to cardiac surveillance and genetic
      testing, and the utility of genotyping for individual risk stratification. As the
      technology for evaluation of the human genome continues to improve, there is an
      increasing need for assessment of clinical relevance and utility. This is coupled
      with an ongoing need for education and training of professionals to interpret and
      implement genomics in a clinical setting.

PMID- 21743788
TI  - Levels of Speech Usage: A Self-Report Scale for Describing How People Use Speech.
AB  - People use speech in a variety of ways to fulfill life roles and
      responsibilities. Documenting speech usage is critical in clinical work to plan
      relevant intervention goals for individual clients, and in clinical research to
      better describe participant characteristics. A few voice-use classification
      scales exist; however, they are limited in scope (e.g., focus almost exclusively
      on occupation) and in applicability beyond voice-disordered populations. The
      Levels of Speech Usage is a self-report categorical rating scale intended for use
      with adults across a wide range of communication disorders and life situations.
      This article presents data from the initial analysis of this scale in a sample of
      200 people with spasmodic dysphonia (SD). Speech usage was significantly
      associated with age, education level, and work status (full time, part time, no
      paid work). Speech usage was not significantly associated with gender, SD
      duration, self-rating of voice, treatment status, presence of other medical
      conditions, Voice Handicap Index, or a measure of communicative participation.
      Further research is needed to explore the function of this scale in other
      populations.

PMID- 21743789
TI  - Estimating Disease Prevalence Using Inverse Binomial Pooled Testing.
AB  - Monitoring populations of hosts as well as insect vectors is an important part of
      agricultural and public health risk assessment. In applications where pathogen
      prevalence is likely low, it is common to test pools of subjects for the presence
      of infection, rather than to test subjects individually. This technique is known
      as pooled (group) testing. In this paper, we revisit the problem of estimating
      the population prevalence p from pooled testing, but we consider applications
      where inverse binomial sampling is used. Our work is unlike previous research in
      pooled testing, which has largely assumed a binomial model. Inverse sampling is
      natural to implement when there is a need to report estimates early on in the
      data collection process and has been used in individual testing applications when
      disease incidence is low. We consider point and interval estimation procedures
      for p in this new pooled testing setting, and we use example data sets from the
      literature to describe and to illustrate our methods.

PMID- 21743790
TI  - Reducing Substance Use and HIV Health Disparities among Hispanic Youth in the
      U.S.A.: The Familias Unidas Program of Research.
AB  - Preventing/reducing substance use and HIV among Hispanic youth is essential to
      eliminating the health disparities that exist between Hispanics and other
      segments of the population. The objective of this article is to describe a
      program of research involving Familias Unidas, a Hispanic-specific, parent
      centered intervention, aimed at reducing substance use and HIV health disparities
      among Hispanic youth. This article will focus on the theoretical foundation of
      the intervention, the empirical research supporting the theoretical model, the
      intervention model itself, the findings of the program of research, and the
      translation of this intervention into community practice.

PMID- 21743791
TI  - Cyclic AMP-guanine exchange factor activation inhibits JNK-dependent
      lipopolysaccharide-induced apoptosis in rat hepatocytes.
AB  - Lipopolysaccharide (LPS) is known to damage hepatocytes by cytokines released
      from activated Kupffer cells, but the ancillary role of LPS as a direct
      hepatotoxin is less well characterized. The aim of this study was to determine
      the direct effect of LPS on hepatocyte viability and the underlying signaling
      mechanism. Rat hepatocyte cultures treated overnight with LPS (500 ng/mL) induced
      apoptosis as monitored morphologically (Hoechst 33258) and biochemically
      (cleavage of caspase 3 and 9 and the appearance of cytochrome C in the
      cytoplasm). LPS-induced apoptosis was additive to that induced by
      glycochenodeoxycholate or Fas ligand, was associated with activation of c-Jun N
      terminal kinase B (JNK) and p38 mitogen-activated protein kinases (MAPK), and
      inhibition of protein kinase (AKT). Inhibition of JNK by SP600125, but not of p38
      MAPK by SB203580 attenuated LPS-induced apoptosis, indicating JNK dependency. CPT
      2-Me-cAMP, an activator of cAMP-GEF, decreased apoptosis due to LPS alone or in
      combination with glycochenodeoxycholate or Fas ligand. CPT-2-Me-cAMP also
      prevented LPS-induced activation of JNK and inhibition of AKT. Taken together,
      these results suggest that LPS can induce hepatocyte apoptosis directly in vitro
      in a JNK-dependent manner and activation of cAMP-GEF protects against the LPS
      induced apoptosis most likely by reversing the effect of LPS on JNK and AKT.

PMID- 21743792
TI  - Drug use trajectory patterns among older drug users.
AB  - To better understand patterns of drug use trajectories over time, it is essential
      to have standard measures of change. Our goal here is to introduce measures we
      developed to quantify change in drug use behaviors. A secondary goal is to
      provide effective visualizations of these trajectories for applied use. We
      analyzed data from a sample of 92 older drug users (ages 45 to 65) to identify
      transition patterns in drug use trajectories across the life course. Data were
      collected for every year since birth using a mixed methods design. The community
      drawn sample of active and former users were 40% female, 50% African American,
      and 60% reporting some college or greater. Their life histories provided
      retrospective longitudinal data on the diversity of paths taken throughout the
      life course and changes in drug use patterns that occurred over time. Bayesian
      analysis was used to model drug trajectories displayed by innovative computer
      graphics. The mathematical techniques and visualizations presented here provide
      the foundation for future models using Bayesian analysis. In this paper we
      introduce the concepts of transition counts, transition rates and
      relapse/remission rates, and we describe how these measures can help us better
      understand drug use trajectories. Depicted through these visual tools,
      measurements of discontinuous patterns provide a succinct view of individual drug
      use trajectories. The measures we use on drug use data will be further developed
      to incorporate contextual influences on the drug trajectory and build predictive
      models that inform rehabilitation efforts for drug users. Although the measures
      developed here were conceived to better examine drug use trajectories, the
      applications of these measures can be used with other longitudinal datasets.

PMID- 21743793
TI  - Investigation of the Reactivity of Oligodeoxynucleotides with Glyoxal and KMnO(4)
      Chemical Probes by Electrospray Ionization Mass Spectrometry.
AB  - The reactions of two well-known chemical probes, glyoxal and potassium
      permanganate (KMnO(4)), with oligodeoxynucleotides were monitored by electrospray
      ionization (ESI) mass spectrometry to evaluate the influence of the sequence of
      DNA, its secondary structure, and interactions with associated ligands on the
      reactivity of the two probes. Glyoxal, a guanine-reactive probe, incorporated a
      mass shift of 58 Da, and potassium permanganate (KMnO(4)) is a thymine-reactive
      probe that resulted in a mass shift of 34 Da. The reactions depended on the
      accessibility of the nucleobases, and the peak abundances of the adducts in the
      ESI-mass spectra were used to quantify the extent of the chemical probe
      reactions. In this study, both mixed-base sequences were studied as well as
      control sequences in which one reactive site was located at the terminus or
      center of the oligodeoxynucleotide while the surrounding bases were a second,
      different nucleobase. In addition, the reactions of the chemical probes with non
      covalent complexes formed between DNA and either actinomycin D or ethidium
      bromide, both known to interact with single strand DNA, were evaluated.

PMID- 21743794
TI  - Plants versus pathogens: an evolutionary arms race.
AB  - The analysis of plant-pathogen interactions is a rapidly moving research field
      and one that is very important for productive agricultural systems. The focus of
      this review is on the evolution of plant defence responses and the coevolution of
      their pathogens, primarily from a molecular-genetic perspective. It explores the
      evolution of the major types of plant defence responses including pathogen
      associated molecular patterns and effector triggered immunity as well as the
      forces driving pathogen evolution, such as the mechanisms by which pathogen
      lineages and species evolve. Advances in our understanding of plant defence
      signalling, stomatal regulation, R gene-effector interactions and host specific
      toxins are used to highlight recent insights into the coevolutionary arms race
      between pathogens and plants. Finally, the review considers the intriguing
      question of how plants have evolved the ability to distinguish friends such as
      rhizobia and mycorrhiza from their many foes.

PMID- 21743795
TI  - Twelve Frequently Asked Questions About Growth Curve Modeling.
AB  - Longitudinal data analysis has long played a significant role in empirical
      research within the developmental sciences. The past decade has given rise to a
      host of new and exciting analytic methods for studying between-person differences
      in within-person change. These methods are broadly organized under the term
      growth curve models. The historical lines of development leading to current
      growth models span multiple disciplines within both the social and statistical
      sciences, and this in turn makes it challenging for developmental researchers to
      gain a broader understanding of the current state of this literature. To help
      address this challenge, the authors pose 12 questions that frequently arise in
      growth curve modeling, particularly in applications within developmental
      psychology. They provide concise and nontechnical responses to each question and
      make specific recommendations for further readings.

PMID- 21743796
TI  - Crystallizing Membrane Proteins in Lipidic Mesophases. A Host Lipid Screen.
AB  - The default lipid for the bulk of the crystallogenesis studies performed to date
      using the cubic mesophase method is monoolein. There is no good reason however,
      why this 18-carbon, cis-monounsaturated monoacylglycerol should be the preferred
      lipid for all target membrane proteins. The latter come from an array of
      biomembrane types with varying properties that include hydrophobic thickness,
      intrinsic curvature, lateral pressure profile, lipid and protein makeup, and
      compositional asymmetry. Thus, it seems reasonable that screening for
      crystallizability based on the identity of the lipid creating the hosting
      mesophase would be worthwhile. For this, monoacylglycerols with differing acyl
      chain characteristics, such as length and olefinic bond position, must be
      available. A lipid synthesis and purification program is in place in the author's
      laboratory to serve this need. In the current study with the outer membrane sugar
      transporter, OprB, we demonstrate the utility of host lipid screening as a means
      for generating diffraction-quality crystals. Host lipid screening is likely to
      prove a generally useful strategy for mesophase-based crystallization of membrane
      proteins.

PMID- 21743797
TI  - Interindividual Differences in Intraindividual Variation: Balancing Internal and
      External Validity.

PMID- 21743798
TI  - Bayesian Functional Data Analysis Using WinBUGS.
AB  - We provide user friendly software for Bayesian analysis of functional data models
      using WinBUGS 1.4. The excellent properties of Bayesian analysis in this context
      are due to: (1) dimensionality reduction, which leads to low dimensional
      projection bases; (2) mixed model representation of functional models, which
      provides a modular approach to model extension; and (3) orthogonality of the
      principal component bases, which contributes to excellent chain convergence and
      mixing properties. Our paper provides one more, essential, reason for using
      Bayesian analysis for functional models: the existence of software.

PMID- 21743799
TI  - Polarizable Simulations with Second order Interaction Model (POSSIM) force field:
      Developing parameters for alanine peptides and protein backbone.
AB  - A previously introduced POSSIM (POlarizable Simulations with Second order
      Interaction Model) force field has been extended to include parameters for
      alanine peptides and protein backbones. New features were introduced into the
      fitting protocol, as compared to the previous generation of the polarizable force
      field for proteins. A reduced amount of quantum mechanical data was employed in
      fitting the electrostatic parameters. Transferability of the electrostatics
      between our recently developed NMA model and the protein backbone was confirmed.
      Binding energy and geometry for complexes of alanine dipeptide with a water
      molecule were estimated and found in a good agreement with high-level quantum
      mechanical results (for example, the intermolecular distances agreeing within ca.
      0.06A). Following the previously devised procedure, we calculated average errors
      in alanine di- and tetra-peptide conformational energies and backbone angles and
      found the agreement to be adequate (for example, the alanine tetrapeptide
      extended-globular conformational energy gap was calculated to be 3.09 kcal/mol
      quantim mechanically and 3.14 kcal/mol with the POSSIM force field). However, we
      have now also included simulation of a simple alpha-helix in both gas-phase and
      water as the ultimate test of the backbone conformational behavior. The resulting
      alanine and protein backbone force field is currently being employed in further
      development of the POSSIM fast polarizable force field for proteins.

PMID- 21743800
TI  - Assessing protein loop flexibility by hierarchical Monte Carlo sampling.
AB  - Loop flexibility is often crucial to protein biological function in solution. We
      report a new Monte Carlo method for generating conformational ensembles for
      protein loops and cyclic peptides. The approach incorporates the triaxial loop
      closure method which addresses the inverse kinematic problem for generating
      backbone move sets that do not break the loop. Sidechains are sampled together
      with the backbone in a hierarchical way, making it possible to make large moves
      that cross energy barriers. As an initial application, we apply the method to the
      flexible loop in triosephosphate isomerase that caps the active site, and
      demonstrate that the resulting loop ensembles agree well with key observations
      from previous structural studies. We also demonstrate, with 3 other test cases,
      the ability to distinguish relatively flexible and rigid loops within the same
      protein.

PMID- 21743801
TI  - Depression Screening in Medically Ill Homecare Elderly.
AB  - PURPOSE: This article provides data on a depression screening model (HOME) in
      acute home health care designed to detect clinical depression among medically ill
      homebound older patients. The model was developed to address the lack of mental
      health services in home health care settings and to specifically improve
      geriatric depression screening as part of routine care. Authors report on the
      concordance of homecare and research interview ratings of depression in older
      homecare patients. DESIGN AND METHODS: Using a prospective cohort design, data
      were collected from 289 elderly patients, aged 65 and older, from a large home
      health care agency to examine depression, cognitive functioning, medical
      comorbidity, functional status, and social isolation. Research interviews used
      the depression module of the structured clinical interview for DSM (SCID).
      RESULTS: The overall prevalence of major depression was 5.7 percent according to
      both homecare and research raters. The prevalence of subthreshold depressive
      disorder was 16.4 percent as reported by research raters. Observed agreement was
      73 percent and kappa agreement was 0.42, indicating a fair to moderate agreement.
      We identified patient characteristics that may influence the accuracy of homecare
      worker estimates of depressive symptoms. IMPLICATIONS: Findings suggest that
      depression continues to be underdetected in medically ill homebound elderly
      patients. Ongoing training in depression screening methods, patient follow-up
      interviews, and appropriate referral would improve care of depressed elderly
      homecare patients.

PMID- 21743802
TI  - Fully Metal-Coated Scanning Near-Field Optical Microscopy Probes with Spiral
      Corrugations for Superfocusing under Arbitrarily Oriented Linearly Polarised
      Excitation.
AB  - We study the effect of a spiral corrugation on the outer surface of a fully metal
      coated scanning near-field optical microscopy (SNOM) probe using the finite
      element method. The introduction of a novel form of asymmetry, devoid of any
      preferential spatial direction and covering the whole angular range of the
      originally axisymmetric tip, allows attaining strong field localization for a
      linearly polarised mode with arbitrary orientation. Compared to previously
      proposed asymmetric structures which require linearly polarised excitation
      properly oriented with respect to the asymmetry, such a configuration enables
      significant simplification in mode injection. In fact, not only is the need for
      the delicate procedure to generate radially polarised beams overcome, but also
      the relative alignment between the linearly polarised beam and the tip
      modification is no longer critical.

PMID- 21743803
TI  - Angiogenin as a molecular target for the treatment of prostate cancer.
AB  - Angiogenin (ANG), a 14 kDa angiogenic ribonuclease, is upregulated in human
      prostate cancers, especially in hormone refractory diseases, and is the highest
      upregulated gene in Akt-driven prostate intraepithelial neoplasia (PIN) in mice.
      ANG has been shown to undergo nuclear translocation in both prostate cancer cells
      and cancer-associated endothelial cells where it binds to the promoter region of
      ribosomal DNA (rDNA) and stimulates ribosomal RNA (rRNA) transcription. ANG thus
      plays an essential role in prostate cancer progression by stimulating both cancer
      cell proliferation and tumor angiogenesis. A variety of ANG antagonists,
      including its antisense oligonucleotide, siRNA, soluble binding proteins,
      monoclonal antibody, enzymatic inhibitors, and nuclear translocation blockers,
      have all been shown to inhibit prostate cancer in various animal models.
      Accumulating evidence indicates that ANG is a molecular target for prostate
      cancer drug development.

PMID- 21743804
TI  - Visual experience modulates spatio-temporal dynamics of circuit activation.
AB  - Persistent reduction in sensory drive in early development results in multiple
      plastic changes of different cortical synapses. How these experience-dependent
      modifications affect the spatio-temporal dynamics of signal propagation in
      neocortical circuits is poorly understood. Here we demonstrate that brief visual
      deprivation significantly affects the propagation of electrical signals in the
      primary visual cortex. The spatio-temporal spread of circuit activation upon
      direct stimulation of its input layer (Layer 4) is reduced, as is the activation
      of L2/3 - the main recipient of the output from L4. Our data suggest that the
      decrease in spatio-temporal activation of L2/3 depends on reduced L4 output, and
      is not intrinsically generated within L2/3. The data shown here suggest that
      changes in the synaptic components of the visual cortical circuit result not only
      in alteration of local integration of excitatory and inhibitory inputs, but also
      in a significant decrease in overall circuit activation. Furthermore, our data
      indicate a differential effect of visual deprivation on L4 and L2/3, suggesting
      that while feedforward activation of L2/3 is reduced, its activation by long
      range, within layer inputs is unaltered. Thus, brief visual deprivation induces
      experience-dependent circuit re-organization by modulating not only circuit
      excitability, but also the spatio-temporal patterns of cortical activation within
      and between layers.

PMID- 21743805
TI  - Functional properties of striatal fast-spiking interneurons.
AB  - Striatal fast-spiking interneurons (FSIs) have a major influence over behavioral
      output, and a deficit in these cells has been observed in dystonia and Tourette
      syndrome. FSIs receive cortical input, are coupled together by gap junctions, and
      make perisomatic GABAergic synapses onto many nearby projection neurons. Despite
      being critical components of striatal microcircuits, until recently little was
      known about FSI activity in behaving animals. Striatal FSIs are near-continuously
      active in awake rodents, but even neighboring FSIs show uncorrelated activity
      most of the time. A coordinated "pulse" of increased FSI firing occurs throughout
      striatum when rats initiate one chosen action while suppressing a highly trained
      alternative. This pulse coincides with a drop in globus pallidus population
      activity, suggesting that pallidostriatal disinhibition may have a important role
      in timing or coordinating action execution. In addition to changes in firing
      rate, FSIs show behavior-linked modulation of spike timing. The variability of
      inter-spike intervals decreases markedly following instruction cues, and FSIs
      also participate in fast striatal oscillations that are linked to rewarding
      events and dopaminergic drugs. These studies have revealed novel and unexpected
      properties of FSIs, that should help inform new models of striatal information
      processing in both normal and aberrant conditions.

PMID- 21743806
TI  - The corticostriatal system in dissociated cell culture.
AB  - The sparse connectivity within the striatum in vivo makes the investigation of
      individual corticostriatal synapses very difficult. Most studies of the
      corticostriatal input have been done using electrical stimulation under
      conditions where it is hard to identify the precise origin of the cortical input.
      We have employed an in vitro dissociated cell culture system that allows the
      identification of individual corticostriatal pairs and have been developing
      methods to study individual neuron inputs to striatal neurons. In mixed
      corticostriatal cultures, neurons had resting activity similar to the system in
      vivo. Up/down states were obvious and seemed to encompass the entire culture.
      Mixed cultures of cortical neurons from transgenic mice expressing green
      fluorescent protein with striatal neurons from wild-type mice of the same
      developmental stage allowed visual identification of individual candidate
      corticostriatal pairs. Recordings were performed between 12 and 37 days in vitro
      (DIV). To investigate synaptic connections we recorded from 69 corticostriatal
      pairs of which 44 were connected in one direction and 25 reciprocally. Of these
      connections 41 were corticostriatal (nine inhibitory) and 53 striatocortical (all
      inhibitory). The observed excitatory responses were of variable amplitude (-10 to
      -370 pA, n = 32). We found the connections very secure - with negligible failures
      on repeated stimulation (approximately 1 Hz) of the cortical neuron. Inhibitory
      corticostriatal responses were also observed (-13 to -314 pA, n = 9). Possibly
      due to the mixed type of culture we found an inhibitory striatocortical response
      (-14 to -598 pA, n = 53). We are now recording from neurons in separate
      compartments to more closely emulate neuroanatomical conditions but still with
      the possibility of the easier identification of the connectivity.

PMID- 21743807
TI  - Informatics and data mining tools and strategies for the human connectome
      project.
AB  - The Human Connectome Project (HCP) is a major endeavor that will acquire and
      analyze connectivity data plus other neuroimaging, behavioral, and genetic data
      from 1,200 healthy adults. It will serve as a key resource for the neuroscience
      research community, enabling discoveries of how the brain is wired and how it
      functions in different individuals. To fulfill its potential, the HCP consortium
      is developing an informatics platform that will handle: (1) storage of primary
      and processed data, (2) systematic processing and analysis of the data, (3) open
      access data-sharing, and (4) mining and exploration of the data. This informatics
      platform will include two primary components. ConnectomeDB will provide database
      services for storing and distributing the data, as well as data analysis
      pipelines. Connectome Workbench will provide visualization and exploration
      capabilities. The platform will be based on standard data formats and provide an
      open set of application programming interfaces (APIs) that will facilitate broad
      utilization of the data and integration of HCP services into a variety of
      external applications. Primary and processed data generated by the HCP will be
      openly shared with the scientific community, and the informatics platform will be
      available under an open source license. This paper describes the HCP informatics
      platform as currently envisioned and places it into the context of the overall
      HCP vision and agenda.

PMID- 21743808
TI  - Successful treatment of epidermal growth factor receptor inhibitor-induced
      periungual inflammation with adapalene.
AB  - Epidermal growth factor receptor (EGFR) inhibitors are increasingly used for
      cancer treatment, but commonly carry dermatologic side effects. Periungual
      inflammation is a particularly painful condition that additionally worsens
      quality of life. In this paper, we report 3 cases of successful treatment of
      periungual inflammation induced by 3 different EGFR inhibitors (gefitinib,
      erlotinib, and cetuximab) with topically applied adapalene.

PMID- 21743809
TI  - Linking speech perception and neurophysiology: speech decoding guided by cascaded
      oscillators locked to the input rhythm.
AB  - The premise of this study is that current models of speech perception, which are
      driven by acoustic features alone, are incomplete, and that the role of decoding
      time during memory access must be incorporated to account for the patterns of
      observed recognition phenomena. It is postulated that decoding time is governed
      by a cascade of neuronal oscillators, which guide template-matching operations at
      a hierarchy of temporal scales. Cascaded cortical oscillations in the theta,
      beta, and gamma frequency bands are argued to be crucial for speech
      intelligibility. Intelligibility is high so long as these oscillations remain
      phase locked to the auditory input rhythm. A model (Tempo) is presented which is
      capable of emulating recent psychophysical data on the intelligibility of speech
      sentences as a function of "packaging" rate (Ghitza and Greenberg, 2009). The
      data show that intelligibility of speech that is time-compressed by a factor of 3
      (i.e., a high syllabic rate) is poor (above 50% word error rate), but is
      substantially restored when the information stream is re-packaged by the
      insertion of silent gaps in between successive compressed-signal intervals - a
      counterintuitive finding, difficult to explain using classical models of speech
      perception, but emerging naturally from the Tempo architecture.

PMID- 21743810
TI  - Type IVB Secretion Systems of Legionella and Other Gram-Negative Bacteria.
AB  - Type IV secretion systems (T4SSs) play a central role in the pathogenicity of
      many important pathogens, including Agrobacterium tumefaciens, Helicobacter
      pylori, and Legionella pneumophila. The T4SSs are related to bacterial
      conjugation systems, and are classified into two subgroups, type IVA (T4ASS) and
      type IVB (T4BSS). The T4BSS, which is closely related to conjugation systems of
      IncI plasmids, was originally found in human pathogen L. pneumophila;
      pathogenesis by L. pneumophila infection requires functional Dot/Icm T4BSS. A
      zoonotic pathogen, Coxiella burnetii, and an arthropod pathogen, Rickettsiella
      grylli - both of which carry T4BSSs highly similar to the Legionella Dot/Icm
      system - are evolutionarily closely related and comprise a monophyletic group. A
      growing body of bacterial genomic information now suggests that T4BSSs are not
      limited to Legionella and related bacteria and IncI plasmids. Here, we review the
      current knowledge on T4BSS apparatus and component proteins, gained mainly from
      studies on L. pneumophila Dot/Icm T4BSS. Recent structural studies, along with
      previous findings, suggest that the Dot/Icm T4BSS contains components with
      primary or higher-order structures similar to those in other types of secretion
      systems - types II, III, IVA, and VI, thus highlighting the mosaic nature of
      T4BSS architecture.

PMID- 21743811
TI  - Secrets of a successful pathogen: legionella resistance to progression along the
      autophagic pathway.
AB  - To proliferate within phagocytes, Legionella pneumophila relies on Type IV
      secretion to modulate host cellular pathways. Autophagy is an evolutionarily
      conserved degradative pathway that captures and transfers a variety of microbes
      to lysosomes. Biogenesis of L. pneumophila-containing vacuoles and autophagosomes
      share several features, including endoplasmic reticulum (ER)-derived membranes,
      contributions by the host GTPases Rab1, Arf1 and Sar1, and a final destiny in
      lysosomes. We discuss morphological, molecular genetic, and immunological data
      that support the model that, although A/J mouse macrophages efficiently engulf L.
      pneumophila within autophagosomal membranes, the Type IV effector proteins
      DrrA/SidM, LidA, and RalF prolong association with the ER. By inhibiting
      immediately delivery to lysosomes, the bacteria persist in immature
      autophagosomal vacuoles for a period sufficient to differentiate into an acid
      resistant, replicative form. Subsequent secretion of the Type IV effector LepB
      releases the block to autophagosome maturation, and the adapted progeny continue
      to replicate within autophagolysosomes. Accordingly, L. pneumophila can be
      exploited as a genetic tool to analyze the recruitment and function of the
      macrophage autophagy pathway.

PMID- 21743812
TI  - Changing nature of cardiac interventions in older adults.
AB  - Older adults represent a rapidly growing segment of the population in developed
      countries. Advancing age is the most powerful risk factor for the development of
      cardiovascular disease (CVD), and CVD-related mortality increases markedly in
      older individuals. Procedures for patients with CVD, including percutaneous
      coronary intervention, aortic valve replacement and implantable cardioverter
      defibrillators were all initially validated in younger individuals but are
      increasingly being applied in older adults who for the most part have been
      significantly understudied in clinical trials. While advanced age alone is not a
      contraindication to these procedures, with the advent of less invasive methods to
      manage CVD including percutaneous techniques to treat both coronary artery
      disease and valvular heart disease, future research will need to weigh the
      potential harms of intervention in a population of older adults with multiple
      medical comorbidities and complex physiologic phenotypes against outcomes that
      include preventing functional decline and improving quality of life.

PMID- 21743813
TI  - Cancer cells' epigenetic composition and predisposition to histone deacetylase
      inhibitor sensitization.
AB  - Normal cells are up to ten times more resistant to histone deacetylase inhibitors
      (HDACis)-induced cell death compared with transformed cells. The molecular
      processes underlying this selectivity for cancer cells are still not well
      understood. Although a differential response to oxidative stress and capacity to
      repair damaged DNA have been described in some systems, these cannot fully
      account for the sensitivity of cancer cells to HDACis since the heterogeneity of
      cancer cells prompts differential sensitivities to reactive oxygen species and
      generates a panoply of defective DNA repair mechanisms within given histologies,
      cancer cell lines and tumor xenografts. It seems also unlikely that the influence
      of HDACis on cancer treatments reside primarily on gene transcription, since gene
      expression profiling aimed at defining correlation with response to HDACis in
      cancer cells indicates that less than 5% to approximately 20% of transcribed
      genes are altered by HDACis treatment. Moreover, the altered genes vary from cell
      line to cell line and between different HDACis. Therefore, no consistent picture
      of a target(s) or pathway(s) modulated by HDACis has emerged. One consistent
      parameter that has however been observed in peripheral blood mononuclear cells of
      patients treated with HDACi is the accumulation of acetylated histones. Because
      one of the primary functions of histone acetylation is to increase chromatin
      accessibility, this article will explore the possibility that intrinsic molecular
      and structural characteristics of cancer cells provide a selective advantage for
      HDACis sensitivity.

PMID- 21743814
TI  - Functional Magnetic Resonance Imaging - Implications for Detection of
      Schizophrenia.
AB  - Functional magnetic resonance imaging (fMRI) is an invaluable non-invasive
      instrument that has been used to investigate physiological disturbances that lead
      to manifest psychiatric illnesses. It is hoped that efficient application of fMRI
      can be utilised to characterise and diagnose mental illnesses such as
      schizophrenia. Although there are various fMRI research studies presenting very
      promising diagnosis results for schizophrenia, we believe that there is much to
      be done to develop effective diagnostic tools for clinical purposes. We present
      specific examples based mostly on our past and recent work together with various
      examples from the recent literature. We discuss where we currently stand in the
      efforts of fMRI being used for diagnosis of schizophrenia, examine common
      possible biases and offer some solutions with the hope that fMRI can be more
      efficiently used in diagnostic research.

PMID- 21743815
TI  - Variations in lipid levels according to menstrual cycle phase: clinical
      implications.
AB  - Understanding variations in lipoprotein cholesterol levels throughout the
      menstrual cycle is important because there may be clinical implications regarding
      the appropriate timing of measurement and implications on the design and
      interpretation of studies in women of reproductive age. Our objective was to
      review the evidence comparing lipoprotein cholesterol levels throughout the
      menstrual cycle among premenopausal women. Overall, lipoprotein cholesterol
      levels were observed to vary in response to changing estrogen levels. Taken
      together, the evidence suggests that total cholesterol and LDL-C tend to be
      highest during the follicular phase and to decline during the luteal phase, with
      HDL C highest around ovulation. Based on these findings, the menstrual cycle
      phase should be taken into account when evaluating lipoprotein cholesterol levels
      among reproductive-aged women. Measuring cholesterol levels during menses is
      recommended for consistent comparisons as this phase can be more reliably
      identified than other phases, although women within National Cholesterol
      Education Program acceptable ranges, but near the boundaries when tested during
      menses, should undergo additional tests.

PMID- 21743816
TI  - The Rules of Variation Expanded, Implications for the Research on Compatible
      Genomics.
AB  - The main focus of this article is to present the practical aspect of the code
      rules of variation and the search for a second set of genomic rules, including
      comparison of sequences to understand how to preserve compatible organisms in
      danger of extinction and how to generate biodiversity. Three new rules of
      variation are introduced: 1) homologous recombination, 2) a healthy fertile
      offspring, and 3) comparison of compatible genomes. The novel search in the
      natural world for fully compatible genomes capable of homologous recombination is
      explored by using examples of human polymorphisms in the LDLRAP1 gene, and by the
      production of fertile offspring by crossbreeding. Examples of dogs, llamas and
      finches will be presented by a rational control of: natural crossbreeding of
      organisms with compatible genomes (something already happening in nature), the
      current work focuses on the generation of new varieties after a careful plan.
      This study is presented within the context of biosemiotics, which studies the
      processing of information, signaling and signs by living systems. I define a
      group of organisms having compatible genomes as a single theme: the genomic
      species or population, able to speak the same molecular language through
      different accents, with each variety within a theme being a different version of
      the same book. These studies have a molecular, compatible genetics context.
      Population and ecosystem biosemiotics will be exemplified by a possible genetic
      damage capable of causing mutations by breaking the rules of variation through
      the coordinated patterns of atoms present in the 9/11 World Trade Center
      contaminated dust (U, Ba, La, Ce, Sr, Rb, K, Mn, Mg, etc.), combination that may
      be able to overload the molecular quality control mechanisms of the human body. I
      introduce here the balance of codons in the circular genetic code:
      2[1(1)+1(3)+1(4)+4(2)]=2[2(2)+3(4)].

PMID- 21743817
TI  - Understanding preventive behaviors among mid-Western African-American men: a
      pilot qualitative study of prostate screening.
AB  - BACKGROUND: African-American men bear a disproportionate burden for disease
      compared to other ethnic and racial groups. Due to gender differences in
      socialization and lifestyle practices, men are more likely to adopt attitudes and
      beliefs that undermine their health and well-being, including beliefs related to
      masculinity. The purpose of this study was to explore and understand the
      contextual factors in the attitudes and beliefs of African-American men's view of
      health in general, and as related to prostate cancer in particular. METHODS:
      Qualitative data from 15 African-American men were collected from two focus
      groups and analyzed for common themes using a qualitative descriptive design.
      RESULTS: Three themes emerged that focused on the beliefs and attitudes regarding
      general health and prostate cancer screening: (i) traditional beliefs about
      masculinity; (ii) psychosocial impact from family medical history; and (iii)
      sexual mores regarding digital rectal exams. CONCLUSIONS: The socialization of
      African-American men and masculinity ideologies may be significant factors in the
      focus group member's decisions to seek preventive health behavior changes.
      Further research is needed to examine the determinants of African-American men's
      health seeking behavior, in particular on the influence of masculine beliefs.

PMID- 21743818
TI  - Discordance in Diagnoses and Treatment of Psychiatric Disorders in Children and
      Adolescents with 22q11.2 Deletion Syndrome.
AB  - This study examines the rate of utilization of mental health services in children
      and adolescents with 22q11DS relative to their remarkably high rate of
      psychiatric disorders and behavior problems. Seventy-two children and adolescents
      with 22q11DS were participants; their parents completed the Diagnostic Interview
      Schedule for Children (DISC) and the Child Behavior Checklist (CBCL). The results
      indicated that 22q11DS children and adolescents have higher rates of
      psychopathology than the general pediatric population, with ADHD and anxiety
      disorders being the most common. However, among youth with 22q11DS, those with
      psychopathology are often no more likely to receive either pharmacological or non
      pharmacological mental health care than those without a given psychiatric
      diagnosis. Thus, although psychopathology is fairly common in this sample, many
      children with 22q11DS may not be receiving needed psychiatric care. These results
      have significant implications for these children and their families, as well as
      for the health care providers who treat them. In particular, the results may
      suggest a need for careful screening of psychiatric disorders that are likely to
      affect this population as well, as making appropriate treatment recommendations
      to remedy childhood mental health problems. Since these children face an
      extraordinarily high risk of psychoses in late adolescence/adulthood, treatment
      of childhood psychopathology could be crucial in mitigating the risk/consequences
      of major psychiatric illnesses in later life.

PMID- 21743819
TI  - Enhanced neural responses to rule violation in children with autism: a comparison
      to social exclusion.
AB  - The present study aimed to explore the neural correlates of two characteristic
      deficits in autism spectrum disorders (ASD); social impairment and restricted,
      repetitive behavior patterns. To this end, we used comparable experiences of
      social exclusion and rule violation to probe potentially atypical neural networks
      in ASD. In children and adolescents with and without ASD, we used the interactive
      ball-toss game (Cyberball) to elicit social exclusion and a comparable game
      (Cybershape) to elicit a non-exclusive rule violation. Using functional magnetic
      resonance imaging (fMRI), we identified group differences in brain responses to
      social exclusion and rule violation. Though both groups reported equal distress
      following exclusion, the right insula and ventral anterior cingulate cortex were
      hypoactive during exclusion in children with ASD. In rule violation, right insula
      and dorsal prefrontal cortex were hyperactive in ASD. Right insula showed a
      dissociation in activation; it was hypoactive to social exclusion and hyperactive
      to rule violation in the ASD group. Further probed, different regions of right
      insula were modulated in each game, highlighting differences in regional
      specificity for which subsequent analyses revealed differences in patterns of
      functional connectivity. These results demonstrate neurobiological differences in
      processing social exclusion and rule violation in children with ASD.

PMID- 21743820
TI  - fMRI of syntactic processing in typically developing children: structural
      correlates in the inferior frontal gyrus.
AB  - Development of syntactic processing was examined to evaluate maturational
      processes including left language lateralization functions and increased
      specialization of brain regions important for syntactic processing. We utilized
      multimodal methods, including indices of brain activity from fMRI during a
      syntactic processing task, cortical thickness measurements from structural MRI,
      and neuropsychological measures. To evaluate hypotheses about increasing
      lateralization and specialization with development, we examined relationships
      between cortical thickness and magnitude and spatial activation extent within the
      left inferior frontal gyrus (IFG) and its right hemisphere homologue. We
      predicted that increased activation in the left and decreased activation in the
      right IFG would be associated with increased syntactic proficiency. As predicted,
      a more mature pattern of increased thickness in the right pars triangularis was
      associated with decreased activation intensity and extent in the right IFG. These
      findings suggest a maturational shift towards decreased involvement of the right
      IFG for syntactic processing. Better syntactic skills were associated with
      increased activation in the left IFG independent from age, suggesting increased
      specialization of the left IFG with increased proficiency. Overall, our findings
      show relationships between structural and functional neurodevelopment that co
      occur with improved syntactic processing in critical language regions of the IFG
      in typically developing children.

PMID- 21743821
TI  - Estimating HIV Incidence in Populations Using Tests for Recent Infection: Issues,
      Challenges and the Way Forward.
AB  - INTRODUCTION: HIV incidence is the rate of new infections in a population over
      time. HIV incidence is a critical indicator needed to assess the status and
      trends of the HIV epidemic in populations and guide and assess the impact of
      prevention interventions.  METHODS: Several methods exist for estimating
      population-level HIV incidence: direct observation of HIV incidence through
      longitudinal follow-up of persons at risk for new HIV infection, indirect
      measurement of HIV incidence using data on HIV prevalence and mortality in a
      population, and direct measurement of HIV incidence through use of tests for
      recent infection (TRIs) that can differentiate "recent" from "non-recent"
      infections based on biomarkers in cross-sectional specimens. Given the
      limitations in measuring directly observed incidence and the assumptions needed
      for indirect measurements of incidence, there is an increasing demand for TRIs
      for HIV incidence surveillance and program monitoring and evaluation purposes. 
      RESULTS: Over ten years since the introduction of the first TRI, a number of low
      , middle-, and high-income countries have integrated this method into their HIV
      surveillance systems to monitor HIV incidence in the population. However, the
      accuracy of these assays for measuring HIV incidence has been unsatisfactory to
      date, mainly due to misclassification of chronic infections as recent infection
      on the assay. To improve the accuracy of TRIs for measuring incidence, countries
      are recommended to apply case-based adjustments, formula-based adjustments using
      local correction factors, or laboratory-based adjustment to minimize error
      related to assay misclassification. Multiple tests may be used in a recent
      infection testing algorithm (RITA) to obtain more accurate HIV incidence
      estimates.  CONCLUSION: There continues to be a high demand for improved TRIs and
      RITAs to monitor HIV incidence, determine prevention priorities, and assess
      impact of interventions. Current TRIs have noted limitations, but with
      appropriate adjustments, interpreted in parallel with other epidemiologic data,
      may still provide useful information on new infections in a population. New TRIs
      and RITAs with improved accuracy and performance are needed and development of
      these tools should be supported.

PMID- 21743822
TI  - Effect of (L:D) Aspect Ratio on Single Polypyrrole Nanowire FET Device.
AB  - Effect of different aspect ratio (length to diameter ratio, L:D) on single
      polypyrrole (Ppy) nanowire based field effect transistor (FET) sensor for real
      time pH monitoring was studied. Ppy nanowires with diameters of ~60, ~80 and ~200
      nm were synthesized using electrochemical deposition inside anodized aluminium
      oxide (AAO) template and were assembled using AC dielectrophoretic alignment
      followed by maskless anchoring on a pair of gold electrodes separated with
      different gap lengths. Microfabricated gold electrode patterns with gap size
      between 1 - 4 MUm were developed by means of MEMS technique (photolithography).
      Using field effect transistor geometry with pair of microfabricated gold contact
      electrodes serving as a source and a drain, and a platinum (Pt) mesh (anchored in
      a microfluidic channel) was used as a gate electrode. When effect of different
      aspect ratio of the nanowire were compared, higher sensitivity was recorded for
      higher aspect ratio. The sensitivity was further improved by modulating the gate
      potential. These FET sensors based on single polypyrrole nanowire exhibited
      excellent and tunable sensitivity towards pH variations.

PMID- 21743823
TI  - Fluorescent Metal Nanoshells: Lifetime-Tunable Molecular Probes in Fluorescent
      Cell Imaging.
AB  - We reported the preparation of lifetime-tunable fluorescent metal nanoshells and
      used them as lifetime imaging agents for potential detection of multiple target
      molecules by a single cell imaging scan. These metal nanoshells were generated to
      have 40 nm silica cores and 10 nm silver shells. Three kinds of metal-ligand
      complexes tris(5-amino-1,10-phenanthroline)ruthenium(II) (Ru(NH(2)-Phen)(3)
      (2+)), tris(2,2'-bipyridine) ruthenium(II) (Ru(bpy)(3) (2+)), and tris(2,3-bis(2
      pyridyl)pyrazine))ruthenium(II) (Ru(dpp)(3) (2+)) that have similar excitation
      and emission wavelengths but different lifetimes were respectively encapsulated
      in the cores of metal nanoshells for the purpose of fluorescence. Compared with
      the metal-free silica spheres, these metal nanoshells were found to display
      enhanced emission intensities and shortened lifetimes due to near-field
      interactions of Ru(II) complexes with the metal shells. The shortened lifetimes
      of these metal nanoshells were definitely unique relevant to the Ru(II)
      complexes: 10 ns for the Ru(Phen-NH(2))(3) (2+)-Ag nanoshells, 45 ns for the
      Ru(bpy)(3) (2+)-Ag nanoshells, and 200 ns for the Ru(dpp)(3) (2+)-Ag nanoshells.
      These lifetimes were longer than the lifetime of cellular autofluorescence (2 - 5
      ns), so the emission signals of these metal nanoshells could be distinctly
      isolated from the cellular background on the lifetime cell images. Moreover,
      these lifetimes were also different from one another, resulting in the emission
      signals of three metal nanoshells could be distinguished from one another on the
      cell images. This feature may offer an opportunity to detect multiple target
      molecules in a single cell imaging scan when the metal nanoshells are bound with
      various targets in the cells.

PMID- 21743824
TI  - Establishment, maintenance and in vitro and in vivo applications of primary human
      glioblastoma multiforme (GBM) xenograft models for translational biology studies
      and drug discovery.
AB  - Development of clinically relevant tumor model systems for glioblastoma
      multiforme (GBM) is important for advancement of basic and translational biology.
      One model that has gained wide acceptance in the neuro-oncology community is the
      primary xenograft model. This model entails the engraftment of patient tumor
      specimens into the flank of nude mice and subsequent serial passage of these
      tumors in the flank of mice. These tumors are then used to establish short-term
      explant cultures or intracranial xenografts. This unit describes detailed
      procedures for establishment, maintenance, and utilization of a primary GBM
      xenograft panel for the purpose of using them as tumor models for basic or
      translational studies.

PMID- 21743825
TI  - Longitudinal functional principal component analysis.
AB  - We introduce models for the analysis of functional data observed at multiple time
      points. The dynamic behavior of functional data is decomposed into a time
      dependent population average, baseline (or static) subject-specific variability,
      longitudinal (or dynamic) subject-specific variability, subject-visit-specific
      variability and measurement error. The model can be viewed as the functional
      analog of the classical longitudinal mixed effects model where random effects are
      replaced by random processes. Methods have wide applicability and are
      computationally feasible for moderate and large data sets. Computational
      feasibility is assured by using principal component bases for the functional
      processes. The methodology is motivated by and applied to a diffusion tensor
      imaging (DTI) study designed to analyze differences and changes in brain
      connectivity in healthy volunteers and multiple sclerosis (MS) patients. An R
      implementation is provided.87.

PMID- 21743826
TI  - Gene Expression Profiles from Peripheral Blood Mononuclear Cells Are Sensitive to
      Short Processing Delays.
AB  - In the analysis of peripheral blood gene expression, timely processing of samples
      is essential to ensure that measurements reflect in vivo biology, rather than ex
      vivo sample processing variables. The effect of processing delays on global gene
      expression patterns in peripheral blood mononuclear cells (PBMCs) was assessed by
      isolating and stabilizing PBMC-derived RNA from 3 individuals either immediately
      after phlebotomy or after a 4 h delay. RNA was labeled using NuGEN Ovation
      labeling and probed using the Affymetrix HG U133 Plus 2.0 GeneChip((r)).
      Comparison of gene expression levels (>=2-fold expression change and P < 0.05)
      identified 307 probe sets representing genes with increased expression and 46
      indicating decreased expression after 4 h. These differentially expressed genes
      include many that are important to inflammatory, immunologic, and cancer
      pathways. Among others, CCR2, CCR5, TLR10, CD180, and IL-16 have decreased
      expression, whereas VEGF, IL8, SOCS2, SOCS3, CD69, and CD83 have increased
      expression after a 4 h processing delay. The trends in expression patterns
      associated with delayed processing were also apparent in an independent set of
      276 arrays of RNA from human PBMC samples with varying processing times. These
      data indicate that the time between sample acquisition, initiation of processing,
      and when the RNA is stabilized should be a prime consideration when designing
      protocols for translational studies involving PBMC gene expression analysis.

PMID- 21743827
TI  - Natural Product Based 6-Hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium
      Scaffold as A New Antifungal Template.
AB  - Synthetic analogues of the marine-derived class of natural products
      phloeodictines have been prepared and exhibited potent in vitro fungicidal
      activities against a broad array of fungal pathogens including drug resistant
      strains. The 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium structural
      moiety with a C12 to C16 aliphatic side chain at C-6 has been shown to be the
      antifungal pharmacophore and may serve as a new antifungal template for further
      lead optimization.

PMID- 21743828
TI  - Characterization and Application of Surface Plasmon-Enhanced Optical Diffraction
      from Electrodeposited Gold Nanowire Arrays.
AB  - Arrays of gold nanowires formed by the process of lithographically patterned
      nanowire electrodeposition (LPNE) were characterized by a combination of SEM,
      polarized UV-visible absorption spectroscopy and optical diffraction
      measurements. A transverse localized surface plasmon resonance (LSPR) was
      observed for gold nanowire arrays with an absorption maximum (lambda(max)) that
      varied with nanowire width. Transmission optical diffraction measurements were
      measured with the even and odd diffraction orders creating an alternating, out of
      phase sinusoidal intensity pattern characteristic of the LPNE nanowire arrays.
      The intensities of the even diffraction order maxima were the strongest for
      nanowires with a width of 115 +/- 10 nm; nanowires of this width exhibit a
      lambda(max) of 635 +/- 10 nm, verifying that the transverse LSPR has enhanced the
      optical diffraction signal. Real time total internal reflection diffraction
      intensity measurements were used to monitor in situ the electrodeposition of
      silver monolayers onto the gold nanowire arrays.

PMID- 21743829
TI  - ANCA: A Family of Fluorescent Probes that Bind and Stain Amyloid Plaques in Human
      Tissue.
AB  - A new family of fluorescent markers containing an Amino Naphthalenyl-2-Cyano
      Acrylate (ANCA) motif has been synthesized and evaluated for its capability to
      associate with aggregated beta-amyloid (Abeta) peptides. These fluorescent probes
      contain a nitrogen donor group that is connected via a naphthalene unit to an
      electron acceptor motif containing Water Solubilizing Groups (WSG). Chemical
      modifications were introduced to explore their effect on the capability of the
      ANCA-based probes to fluorescently label aggregated Abeta peptides. All
      synthesized probes bind to aggregated Abeta fibrils with low micromolar affinity
      and fluorescently stain amyloid deposits in human brain tissue from patients with
      Alzheimer's disease. We found that structural modifications of the WSG site do
      not affect considerably the binding affinity. However, changes of the nitrogen
      donor group alter significantly the binding affinity of these probes. Also,
      increasing the hydrophilicity of the donor group leads to improved contrast
      between the Abeta deposits and the surrounding tissue in histological staining
      experiments.

PMID- 21743830
TI  - Enhancing the Pharmacokinetic Properties of Botulinum Neurotoxin Serotype A
      Protease Inhibitors Through Rational Design.
AB  - Botulinum neurotoxin (BoNT), the etiological agent that causes the neuroparalytic
      disease botulism, has become a highly studied drug target in light of the
      potential abuse of this toxin as a weapon of bioterrorism. In particular, small
      molecule inhibitors of the light chain metalloprotease of BoNT serotype A have
      received significant attention and a number of small molecule and biologic
      inhibitors have been reported. However, all small molecules reported have been
      identified from either primary screens or medicinal chemistry follow-up studies,
      and the pharmacokinetic profiles of these compounds have not been addressed. In
      this study, we have removed the pharmacologic liabilities of one of the best
      compounds reported to date, 2,4-dichlorocinnamate hydroxamic acid, and in the
      process, uncovered a related class of benzothiophene hydroxamic acids that are
      significantly more potent inhibitors of the BoNT/A light chain, while also
      possessing greatly improved ADME properties, with the best compound showing the
      most potent inhibition of BoNT/A light chain reported (K(i) = 77 nM). Using a
      strategy of incorporating traditional drug development filters early into the
      discovery process, potential liabilities in BoNT/A lead compounds have been
      illuminated and removed, clearing the path for advancement into further
      pharmacologic optimization and in vivo efficacy testing.

PMID- 21743831
TI  - Biokinetic Mechanisms Linked With Musculoskeletal Health Disparities: Stochastic
      Models Applying Tikhonov's Theorem to Biomolecule Homeostasis.
AB  - Multiscale technology and advanced mathematical models have been developed to
      control and characterize physicochemical interactions, respectively, enhancing
      cellular and molecular engineering progress. Ongoing tissue engineering
      development studies have provided experimental input for biokinetic models
      examining the influence of static or dynamic mechanical stimuli (Saha, A. K., and
      Kohles, S. S., 2010, "A Distinct Catabolic to Anabolic Threshold Due to Single
      Cell Nanomechanical Stimulation in a Cartilage Biokinetics Model," J.
      Nanotechnol. Eng. Med., 1(3) p. 031005; 2010, "Periodic Nanomechanical
      Stimulation in a Biokinetics Model Identifying Anabolic and Catabolic Pathways
      Associated With Cartilage Matrix Homeostasis," J. Nanotechnol. Eng. Med., 1(4),
      p. 041001). In the current study, molecular regulatory thresholds associated with
      specific disease disparities are further examined through applications of
      stochastic mechanical stimuli. The results indicate that chondrocyte
      bioregulation initiates the catabolic pathway as a secondary response to control
      anabolic processes. In addition, high magnitude loading produced as a result of
      stochastic input creates a destabilized balance in homeostasis. This latter
      modeled result may be reflective of an injurious state or disease progression.
      These mathematical constructs provide a framework for single-cell
      mechanotransduction and may characterize transitions between healthy and disease
      states.

PMID- 21743832
TI  - Human T-cell lymphotropic virus: a model of NF-kappaB-associated tumorigenesis.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult
      T-cell leukemia/lymphoma (ATL), whereas the highly related HTLV-2 is not
      associated with ATL or other cancers. In addition to ATL leukemogenesis, studies
      of the HTLV viruses also provide an exceptional model for understanding basic
      pathogenic mechanisms of virus-host interactions and human oncogenesis.
      Accumulating evidence suggests that the viral regulatory protein Tax and host
      inflammatory transcription factor NF-kappaB are largely responsible for the
      different pathogenic potentials of HTLV-1 and HTLV-2. Here, we discuss the
      molecular mechanisms of HTLV-1 oncogenic pathogenesis with a focus on the
      interplay between the Tax oncoprotein and NF-kappaB pro-oncogenic signaling. We
      also outline some of the most intriguing and outstanding questions in the fields
      of HTLV and NF-kappaB. Answers to those questions will greatly advance our
      understanding of ATL leukemogenesis and other NF-kappaB-associated tumorigenesis
      and will help us design personalized cancer therapies.

PMID- 21743833
TI  - Frontiers in Alzheimer's disease therapeutics.
AB  - Alzheimer disease (AD) is a progressive neurodegenerative disease which begins
      with insidious deterioration of higher cognition and progresses to severe
      dementia. Clinical symptoms typically involve impairment of memory and at least
      one other cognitive domain. Because of the exponential increase in the incidence
      of AD with age, the aging population across the world has seen a congruous
      increase AD, emphasizing the importance of disease altering therapy. Current
      therapeutics on the market, including cholinesterase inhibitors and N-methyl-D
      aspartate receptor antagonists, provide symptomatic relief but do not alter
      progression of the disease. Therefore, progress in the areas of prevention and
      disease modification may be of critical interest. In this review, we summarize
      novel AD therapeutics that are currently being explored, and also mechanisms of
      action of specific drugs within the context of current knowledge of AD pathologic
      pathways.

PMID- 21743834
TI  - Stable singlet carbenes as mimics for transition metal centers.
AB  - This perspective summarizes recent results, which demonstrate that stable
      carbenes can activate small molecules (CO, H(2), NH(3) and P(4)) and stabilize
      highly reactive intermediates (main group elements in the zero oxidation state
      and paramagnetic species). These two tasks were previously exclusive for
      transition metal complexes.

PMID- 21743835
TI  - The Impact of Sample Storage Time on Estimates of Association in Biomarker
      Discovery Studies.
AB  - BACKGROUND: Using serum, plasma or tumor tissue specimens from biobanks for
      biomarker discovery studies is attractive as samples are often readily available.
      However, storage over longer periods of time can alter concentrations of proteins
      in those specimens. We therefore assessed the bias in estimates of association
      from case-control studies conducted using banked specimens when maker levels
      changed over time for single markers and also for multiple correlated markers in
      simulations. Data from a small laboratory experiment using serum samples guided
      the choices of simulation parameters for various functions of changes of
      biomarkers over time. RESULTS: In the laboratory experiment levels of two serum
      markers measured at sample collection and again in the same samples after
      approximately ten years in storage increased by 15%. For a 15% increase in marker
      levels over ten years, odds ratios (ORs) of association were significantly
      underestimated, with a relative bias of -10%, while for a 15% decrease in marker
      levels over time ORs were too high, with a relative bias of 20%. CONCLUSION:
      Biases in estimates of parameters of association need to be considered in sample
      size calculations for studies to replicate markers identified in exploratory
      analyses.

PMID- 21743836
TI  - Associations Between Mothers' and Their Children's Weights at 4 Years of Age.
AB  - OBJECTIVES: To examine the importance of maternal weight characteristics as
      predictors of overweight (BMI >=85th percentile and <95th percentile) and obesity
      (BMI >= 95th percentile) in offspring at age 4 years. METHODS: Chi-square and
      logistic regression analyses were conducted on a sample of 321 mother/child pairs
      from an earlier observational cohort study on mothers' postpartum weight
      retention. RESULTS: Maternal early pregnancy BMI and infant birth weight were
      each positively and significantly (p <0.05) associated with increased risk of
      obesity in offspring at age 4 years. A significant interaction was found between
      these two variables in predicting children's risk of obesity. It was driven by
      the high proportion of obese children among obese women who had infants weighing
      < 3 kg at birth. Net gestational weight gain was not associated with obesity risk
      in children, but was positively associated with infant birth weight among normal
      weight and overweight women. CONCLUSIONS: Reducing maternal BMI in the
      preconception period among overweight and obese women and preventing excessive
      weight gain in pregnancy for all women appear to be appropriate strategies to
      address the childhood obesity epidemic.

PMID- 21743837
TI  - Effect of CBT on Depressive Symptoms in Methadone Maintenance Patients Undergoing
      Treatment for Hepatitis C.
AB  - To examine the efficacy of a cognitive-behavioral intervention (CBT) to prevent
      depression among methadone maintenance patients undergoing antiviral treatment
      for hepatitis C (HCV), 29 patients beginning HCV treatment were randomized to CBT
      or standard care (SC). Study participants did not meet criteria for major
      depressive disorder at the time of study recruitment. CBT did not result in less
      depression-related antiviral treatment failure, better adherence to antiviral
      treatment, or better HCV RNA outcomes. There were no significant treatment group
      differences on depressive symptoms over time. The CBT group did display a greater
      and more consistent decline in both BDI-II and HAM-D scores over time (d=.85 on
      the BDI-II; d=.72 on the HAM-D).

PMID- 21743838
TI  - FHIT gene expression is repressed by mitogenic signaling through the
      PI3K/AKT/FOXO pathway.
AB  - The Fragile Histidine Triad gene or FHIT functions as tumor suppressor in many
      epithelial cell types. Although its tumor suppressive mechanism is the subject of
      intense study, less is known about how FHIT gene expression itself is regulated.
      Here we show that PI3 kinase and its downstream target AKT suppress FHIT gene
      expression in response to growth factor stimulation in actively cycling cells.
      Upon removal of mitogens from the culture environment, FHIT mRNA and protein
      levels are observed to increase as a result of derepression from these
      protooncogenic kinases. AKT signaling through the FOXO transcription factors
      appears to be the basis for FHIT gene regulation. Increases in FHIT gene
      expression are directly dependent on endogenous FOXO3a in MCF7 breast carcinoma
      cells as evidenced by experiments with RNAi targeting FOXO transcription factor
      family members. Thus, this is the first report demonstrating that FHIT gene
      expression is normally repressed in actively cycling cells through the
      PI3K/AKT/FOXO3a axis.

PMID- 21743839
TI  - Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative
      Structure-activity Relationships.
AB  - Photosensitive dyes or photo sensitizers (PS) in combination with visible light
      and oxygen produce reactive oxygen species that kill cells in the process known
      as photodynamic therapy (PDT). Antimicrobial PDT employs PS that is selective for
      microbial cells and is a new treatment for infections. Most antimicrobial PS is
      based on tetrapyrrole or phenothiazinium structures that have been synthesized to
      carry quaternary cationic charges or basic amino groups. However we recently
      showed that cationic-substituted fullerene derivative were highly effective in
      killing a broad spectrum of microbial cells after illumination with white light.
      In the present report we compared a new group of synthetic fullerene derivatives
      that possessed either basic or quaternary amino groups as antimicrobial PS
      against Gram-positive (Staphylococcus aureus), Gram-negative bacteria
      (Escherichia coli) and fungi (Candida albicans). Quantitative structure-function
      relationships were derived with LogP and hydrophilic lipophilic balance
      parameters. Compounds with non-quaternary amino groups tended to form
      nanoaggregates in water and were only effective against S. aureus. The most
      important determinant of effectiveness was an increased number of quaternary
      cationic groups that were widely dispersed around the fullerene cage to minimize
      aggregation. S. aureus was most susceptible; E. coli was intermediate, while C.
      albicans was the most resistant species tested. The high effectiveness of
      antimicrobial PDT with quaternized fullerenes suggest they may have applications
      in treatment of superficial infections (for instance in wounds and burns) where
      light penetration into tissue is not problematic.

PMID- 21743840
TI  - Mass spectrometry-based identification of protein kinase substrates utilizing
      engineered kinases and thiophosphate labeling.
AB  - Protein kinases constitute a large enzyme family with key roles in cellular
      signal transduction. One way to elucidate the functions of protein kinases is to
      systematically identify their downstream targets. We present here a simple and
      effective method to identify direct protein kinase substrates in native cell
      lysates. First, we isolate the activity of the kinase of interest by engineering
      the normal kinase to utilize bulky ATP analogs that cannot be used by normal
      cellular kinases. This allows specific labeling of substrates with thiophosphate
      tags by performing kinase reactions in cell lysates that also include bulky ATP
      gamma-S analogs. After digesting the proteins in the reaction mixture,
      thiophosphopeptides are isolated using a single-step capture-and-release protocol
      and identified by mass spectrometry. This technique is easy to use and generally
      applicable.

PMID- 21743841
TI  - Echocardiography in Mice.
AB  - Murine models have been utilized with increasing frequency mainly due to
      availability of genetically engineered models. With advancement in high spatial
      and temporal resolution, echocardiography is used extensively for the evaluation
      of cardiovascular function in murine models of cardiovascular disease. This
      review summarizes the general applications and methods involved in
      echocardiography used to study mouse models for cardiovascular research, based on
      20 years of experience in our laboratory. The goal of this article is to provide
      a practical guide to the use of echo techniques in mice to evaluate cardiac
      systolic and diastolic function.

PMID- 21743842
TI  - Heart Rate and Electrocardiography Monitoring in Mice.
AB  - The majority of current cardiovascular research involves studies in genetically
      engineered mouse models. The measurement of heart rate is central to
      understanding cardiovascular control under normal conditions, with altered
      autonomic tone, superimposed stress or disease states, both in wild type mice as
      well as those with altered genes. Electrocardiography (ECG) is the "gold
      standard" using either hard wire or telemetry transmission. In addition, heart
      rate is measured or monitored from the frequency of the arterial pressure pulse
      or cardiac contraction, or by pulse oximetry. For each of these techniques,
      discussions of materials and methods, as well as advantages and limitations are
      covered. However, only the direct ECG monitoring will determine not only the
      precise heart rates but also whether the cardiac rhythm is normal or not.

PMID- 21743843
TI  - The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface.
AB  - Preeclampsia (PE) impacts 8 million mother-infant pairs worldwide each year. This
      human pregnancy-specific disease characterized by hypertension and proteinuria
      accounts for significant maternal and neonatal morbidity and mortality. The
      current theory of the pathogenesis of PE as reviewed by Drs. Christopher Redman
      and Ian Sargent is thought to occur as a 2-stage process with poor placentation
      in the first half of pregnancy resulting in the maternal response in the second
      half of pregnancy. Our studies have focused on understanding the placental
      contribution to this serious disease by examining the gene expression profile of
      the deciduas basalis or basal plate, the region of the placenta involved in the
      "poor placentation". In this review we present summaries of our microarray
      datasets both of normal placentation and those gene expression changes resulting
      in the context of PE. Additionally, we have taken this opportunity to combine the
      data sets to provide a more comprehensive view of this region of the placenta. As
      defects in the basal plate are, in part, at the root of the disease process, we
      believe that understanding the pathobiology that occurs in this region will
      increase our ability to alter the development and/or course of PE. 

PMID- 21743844
TI  - BRAIN PATTERN ANALYSIS OF CORTICAL VALUED DISTRIBUTIONS.
AB  - We introduce a new representation of cortical regions via distribution functions
      of their features. The distribution functions are estimated non-parametrically
      from the data and are observed to be non Gaussian. Cortical pattern matching is
      enabled by using the information-based Jensen-Shannon divergence as a measure
      between features. Our approach explicitly avoids pairwise registrations between
      brains, but instead focuses on modeling and discriminating between the cortical
      structural patterns. We demonstrate our approach on 120 subject brains from an
      Alzheimer's dataset, and present applications to clustering, classification, and
      dimension reduction.

PMID- 21743845
TI  - Vowel Recognition from Articulatory Position Time-Series Data.
AB  - A new approach of recognizing vowels from articulatory position time-series data
      was proposed and tested in this paper. This approach directly mapped articulatory
      position time-series data to vowels without extracting articulatory features such
      as mouth opening. The input time-series data were time-normalized and sampled to
      fixed-width vectors of articulatory positions. Three commonly used classifiers,
      Neural Network, Support Vector Machine and Decision Tree were used and their
      performances were compared on the vectors. A single speaker dataset of eight
      major English vowels acquired using Electromagnetic Articulograph (EMA) AG500 was
      used. Recognition rate using cross validation ranged from 76.07% to 91.32% for
      the three classifiers. In addition, the trained decision trees were consistent
      with articulatory features commonly used to descriptively distinguish vowels in
      classical phonetics. The findings are intended to improve the accuracy and
      response time of a real-time articulatory-to-acoustics synthesizer.

PMID- 21743846
TI  - Use of epidermal growth factor receptor mutation analysis in patients with
      advanced non-small-cell lung cancer to determine erlotinib use as first-line
      therapy.
AB  - Lung cancer is the second most common cancer and the leading cause of cancer
      related deaths in the United States. Moreover, advanced non-small-cell lung
      cancer (NSCLC) is considered an incurable disease and current treatment
      approaches provide marginal improvement in overall survival at the expense of
      substantial morbidity and mortality, highlighting the need for new, less toxic
      treatment approaches. Tyrosine kinase inhibitors, such as erlotinib (Tarceva(r)),
      have been developed and approved as maintenance, second- and third-line treatment
      options in unselected advanced NSCLC patients (2, 15). However, subgroup analyses
      from the initial clinical trials consistently showed that patients with epidermal
      growth factor receptor (EGFR) mutations who received erlotinib had higher rates
      of response and better progression-free and overall survival, leading to clinical
      trials specifically focused on the use of tyrosine kinase inhibitors as first
      line therapy in these patients. We examined the published literature on the
      analytic validity, clinical validity, and clinical utility of EGFR mutational
      testing in guiding first-line therapy use of erlotinib to treat advanced NSCLC
      and we briefly summarized the current lung cancer screening guidelines. The
      primary goal was to provide a basic overview of EGFR mutational testing and use
      of erlotinib as first-line therapy and identify gaps in knowledge and evidence
      that affect the recommendation and adoption of the test in advanced NSCLC
      treatment management strategies.

PMID- 21743847
TI  - Genetic testing for lynch syndrome in individuals newly diagnosed with colorectal
      cancer to reduce morbidity and mortality from colorectal cancer in their
      relatives.
AB  - Individuals with Lynch syndrome, sometimes referred to as hereditary non
      polyposis colorectal cancer (HNPCC), have an increased risk of developing
      colorectal cancer (CRC) as well as other cancers. The increased risk is due to
      inherited mutations in mismatch repair (MMR) genes, which reduce the ability of
      cells to repair DNA damage. Screening for Lynch syndrome in individuals newly
      diagnosed with colorectal cancer has been proposed as part of a strategy that
      combines tests and interventions to reduce the risk of colorectal cancer in the
      relatives of the colorectal cancer patients with Lynch Syndrome.

PMID- 21743848
TI  - Nutrition care in general practice - are we waiting for patients to ask?
AB  - General practitioner encounters for chronic disease management increased
      considerably between 1998 and 2008. In particular, patients presenting for the
      management of hypertension increased from 8.3 to 9.9 per 100 encounters; type 2
      diabetes mellitus from 2.6 to 3.7 per 100 encounters; and lipid disorders from
      2.5 to 3.7 per 100 encounters. In 2010, chronic disease management was estimated
      to comprise over one-third of the average GP's consultation workload.

PMID- 21743849
TI  - Eczema.
AB  - From April 2008 to March 2010 in BEACH (Bettering the Evaluation and Care of
      Health), eczema was managed at a rate of 1.5 per 100 encounters, suggesting that
      it was managed by general practitioners about 1.8 million times per year
      nationally.

PMID- 21743850
TI  - Psoriasis.
AB  - BACKGROUND: Psoriasis is one of the more common rashes presenting to general
      practice. OBJECTIVE: This article outlines the assessment and management of
      psoriasis in the general practice setting. DISCUSSION: Careful clinical
      assessment will usually lead to a diagnosis of psoriasis. Management starts with
      education, lifestyle measures and general skin care measures. Although topical
      steroids are the mainstay of treatment, other topical options are outlined and
      treatment options in difficult locations are considered. The potential
      indications for referral and systemic therapies are also considered.

PMID- 21743851
TI  - Hair and nails.
AB  - BACKGROUND: Hair and nails are elements of dermatology that can often be omitted
      from the dermatological assessment. However, there are common and distressing
      hair and nail conditions that require diagnosis and management. OBJECTIVE: This
      article considers common and important hair and nail presentations to general
      practice. General and specific conditions will be discussed. DISCUSSION: Hair
      conditions may have significant psychological implications. This article
      considers assessment and management of conditions of too much hair, hair loss or
      hair in the wrong places. It also considers the common nail conditions seen in
      general practice and provides a guide to diagnosis and management.

PMID- 21743852
TI  - Exanthems and drug reactions.
AB  - BACKGROUND: Drug reactions are a common cause of rashes and can vary from brief,
      mildly annoying, self limiting rashes to severe conditions involving multiple
      organ systems. OBJECTIVE: This article outlines an approach to exanthems that may
      be related to drug reactions and details appropriate management. DISCUSSION:
      Rashes related to drug reactions are both nonallergic and allergic. Nonallergic
      rashes are usually predictable and may be avoidable. Allergic rashes include
      morbilliform erythema, urticaria and angioedema, erythema multiforme and
      vasculitic rashes. The vast majority of cases are rapidly resolving and self
      limiting once the offending agent is removed. Early recognition and supportive
      measures are the keys to care in the majority of cases. However, an awareness of
      serious drug reactions (Stevens- Johnson syndrome and toxic epidermal
      necrolysis), which are potentially life threatening conditions and require
      immediate specialist assessment and treatment in hospital, is important.

PMID- 21743853
TI  - Common vulval dermatoses.
AB  - BACKGROUND: The vulva is skin, and it is helpful to approach vulval conditions
      from a dermatological perspective. The vulva is affected by the same dermatoses
      as the rest of the skin, but modified in appearance by special influences.
      OBJECTIVE: This article will outline an approach to the diagnosis and management
      of vulval dermatoses. DISCUSSION: Vulval disorders present as infections, rashes
      and lesions, and pain. This article considers inflammatory vulval disorders that
      present as erythematous rashes, pallor or erosions and ulcers. Most vulval
      dermatoses are recurrent or chronic and may require maintenance therapy. Chronic
      painful and itchy vulval conditions can lead to secondary pelvic floor spasm and
      a sensory neuropathy. Many vulval disorders are multifactorial and can benefit
      from a multidisciplinary approach to management.

PMID- 21743854
TI  - Prostate specific antigen.
AB  - This article forms part of our 'Tests and results' series for 2011 which aims to
      provide information about common tests that general practitioners order
      regularly. It considers areas such as indications, what to tell the patient, what
      the test can and cannot tell you, and interpretation of results.

PMID- 21743855
TI  - Patient information - what is a PSA test?
AB  - Prostate specific antigen (PSA) is a protein produced by the prostate. The PSA
      test can potentially be used for screening, monitoring, or diagnosis.

PMID- 21743856
TI  - Persistent hoarseness - a case study.
AB  - Marion, a university lecturer aged 48 years, presented to her general
      practitioner complaining of persistent hoarseness for 4-5 weeks. Over the
      preceding 5 months she had suffered two prolonged episodes of bacterial sinusitis
      and an infective exacerbation of her asthma, each requiring several weeks of
      various antibiotics and oral prednisone, and each associated with transient
      hoarseness.

PMID- 21743857
TI  - Multiple facial plaques - a case study.
AB  - Mrs AA, female, 27 years of age and of Middle Eastern descent, presented with a 1
      year history of nonpruritic facial plaques. On examination, these plaques were
      0.2-1.0 cm, scaly, atrophic, annular, hyperpigmented and located on her forehead,
      nose, chin and adjacent to her lips.

PMID- 21743858
TI  - Adult intraosseous access - experiences in a remote emergency department.
AB  - Difficult intravenous access can be a very stressful experience, especially in a
      remote emergency department. Adult intraosseous access can provide rapid access
      for fluids and drugs in a critically ill patient in whom intravenous access is
      difficult or impossible. This article presents two case reports of patients in
      whom rapid intraosseous access was lifesaving.

PMID- 21743859
TI  - Cosmetic surgery on children - professional and legal obligations in Australia.
AB  - BACKGROUND: Public awareness and concern about cosmetic surgery on children is
      increasing. Nationally and internationally questions have been raised by the
      media and government bodies about the appropriateness of children undergoing
      cosmetic surgery. Considering the rates of cosmetic surgery in comparable Western
      societies, it seems likely that the number of physicians in Australia who will
      deal with a request for cosmetic surgery for a child will continue to increase.
      This is a sensitive issue and it is essential that physicians understand the
      professional and legal obligations that arise when cosmetic surgery is proposed
      for a child. OBJECTIVE: This article reviews the current professional and legal
      obligations that physicians have to competent and incompetent children for whom
      cosmetic surgery has been requested. DISCUSSION: A case study is used to
      highlight the factors that Australian primary care physicians must consider
      before referring and conducting cosmetic surgery on children.

PMID- 21743860
TI  - Primary palliative care - facing twin challenges.
AB  - As Australia's population ages, three things are inevitable: more people will
      develop chronic illnesses; more will grow very ill and more will die. Blueprints
      for the future suggest an increasingly important role for general practitioners
      and primary healthcare in palliative care.

PMID- 21743861
TI  - Cholesterol lowering medication - patients' knowledge, attitudes and experiences.
AB  - BACKGROUND: Despite evidence of the efficacy of cholesterol lowering medication,
      it is known there is suboptimal patient adherence to this medication. The aim of
      this study is to investigate patient knowledge, attitudes and experiences of
      their cholesterol lowering medication, and explore patient views regarding
      programs to support self management. METHODS: A semiqualitative exploratory study
      using semistructured telephone interviews of adult patients with poorly
      controlled hyperlipidaemia. RESULTS: Twenty-six patients were interviewed. Most
      patients could name at least one risk factor for their hyperlipidaemia.
      Approximately one-third of patients reported they did not understand the reasons
      they were taking their cholesterol medication and over two-thirds did not
      understand how their medication worked. Most reported that their general
      practitioner was their main source of information about cholesterol. Many
      expressed a desire to be better informed about cholesterol, its risk factors and
      medication and that an information session at their local general practice clinic
      would be useful. DISCUSSION: This study provides preliminary evidence that
      patients on long term statin therapy may have gaps in their knowledge about their
      condition and treatment options and a desire to be better informed.

PMID- 21743862
TI  - AUSDRISK - application in general practice.
AB  - BACKGROUND: The Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK) has
      been promoted since July 2008. We studied its application rate and the profile of
      a sample of general practice patients within Central West New South Wales from
      June to December 2010. METHODS: Stage one assessed the awareness and application
      of AUSDRISK among general practitioners and general practice registrars. In stage
      two, the doctors used AUSDRISK and appropriate blood tests to screen patients
      aged 25-74 years who had not been previously diagnosed with diabetes. RESULTS:
      Seventy-eight doctors (response rate 45.1%) completed the survey. A total of
      68.2% of general practice registrars and 23.2% of GPs were aware of AUSDRISK.
      Among the respondents 14.1% (95% CI: 6-22%) applied AUSDRISK in their usual
      practice, and 39.1% (95% CI: 31-47%) of the 151 patients had high AUSDRISK scores
      >=15. DISCUSSION: Two years after the launch of AUSDRISK, the application rate of
      AUSDRISK is low. In this patient population, many patients had high AUSDRISK
      scores.

PMID- 21743863
TI  - Nondiabetic retinal pathology - prevalence in diabetic retinopathy screening.
AB  - OBJECTIVE: To determine the prevalence of photographic signs of nondiabetic
      retinal pathology in Australian general practice patients with diabetes. METHOD:
      Three hundred and seven patients with diabetes underwent retinal photography at
      two general practices, one of which was an indigenous health centre. The images
      were assessed for signs of pathology by an ophthalmologist. RESULTS: Signs of
      nondiabetic retinal pathology were detected in 31% of subjects with adequate
      photographs. Features suspicious of glaucoma were detected in 7.7% of subjects.
      Other abnormalities detected included signs of age related macular degeneration
      (1.9%), epiretinal membranes (2.4%), vascular pathology (9.6%), chorioretinal
      lesions (2.9%), and congenital disc anomalies (2.9%). Indigenous Australian
      patients were more likely to have signs of retinal pathology and glaucoma.
      CONCLUSION: Signs of nondiabetic retinal pathology were frequently encountered.
      In high risk groups, general practice based diabetic retinopathy screening may
      reduce the incidence of preventable visual impairment, beyond the benefits of
      detection of diabetic retinopathy alone.

PMID- 21743864
TI  - Chronic hepatitis B - a clinical audit of GP management.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection represents a growing health burden
      in Australia. This clinical audit aimed to enhance general practitioner awareness
      of the recommended management for patients with chronic hepatitis B. OBJECTIVE:
      This article describes a clinical two-phase audit of 119 Australian GPs who
      contributed records retrospectively of patients with chronic hepatitis B.
      DISCUSSION: Patient records were examined for compliance with prevailing
      guidelines and GPs received education on guidelines. At completion of the audit
      29% of patients were monitored at recommended intervals and 47% were managed
      according to the current guidelines. Recording of hepatitis B virus DNA results
      increased from 24% in phase 1 to 63% in phase 2. General practitioners reported
      increased knowledge of appropriate management and referral. Twenty-five percent
      of patients audited in both phases had been referred to a specialist.
      Participating GPs improved their management of patients with chronic hepatitis B.
      However, there remains considerable scope for enhancing GP understanding of
      hepatitis B virus and applying current guidelines to clinical practice.

PMID- 21743865
TI  - The pre-employment medical - nuisance or great opportunity?
AB  - BACKGROUND: Requests for general practitioners to conduct pre-employment medicals
      are increasing, encouraged by the increasing costs of workplace injuries,
      insurance claims, premiums and common law claims. In many industries, especially
      mining and natural gas, legislation demands that a medical be undertaken before
      the employee is allowed onsite. OBJECTIVE: This article describes the nature of a
      pre-employment medical and the role of the GP in providing a medical. It also
      provides tips on how to make the medical part of a preventive health assessment.
      DISCUSSION: Pre-employment medicals are often unpopular as practices struggle to
      cope with excessive workloads. However, with good time management, prior
      assessment of the supplied paperwork and the addition of some further questions
      on health and lifestyle, medicals can provide a good assessment of a patient and
      assist in the prevention or management of potential or chronic health problems.
      The medical also provides an excellent opportunity to promote health and to
      assist in disease and injury prevention by providing feedback for a healthier
      lifestyle and injury prevention. This is an especially great opportunity for male
      patients, who rarely visit their GP for routine health checks.

PMID- 21743866
TI  - Symptoms of rhinosinusitis.

PMID- 21743867
TI  - Osteitic bone in recalcitrant chronic rhinosinusitis.
AB  - INTRODUCTION: There is increasing interest in the underlying bone of the
      paranasal sinuses as an important player in recalcitrant Chronic Rhinosinusitis.
      Close inspection of CT scans often reveals areas of increased bone density and
      irregular thickening of the sinus walls. This osteitic bone could at least partly
      explain, why inflammation of the mucosa persists. METHODS: We searched PubMed for
      all relevant studies, using the following text words: chronic rhinosinusitis,
      sinusitis, bone, osteitis, osteomyelitis, histology, and treatment. Cited
      references of retrieved articles were also examined. RESULTS: Background,
      available data, potential diagnostic options, treatment implications, and
      suggestions for future research are discussed. CONCLUSION: Osteitis is associated
      with CRS, however its role in the pathogenic process is not well defined. More
      research is needed.

PMID- 21743868
TI  - Osteogenic potential of cells derived from nasal septum.
AB  - BACKGROUND: The research addressed to detect new molecular targets in the
      development of therapeutic strategies aimed to repair bone tissues. The AIM OF
      THIS STUDY was to determine the potential osteogenic activity of bone cells from
      the nasal septum and their use to perform accurate molecular analysis from a
      single sample. METHODOLOGY: The cells, after nasal septum surgery, were subjected
      to gene silencing, Reverse Transcriptase - Polymerase Chain reactions,
      immunocytochemistry and chromatin immunoprecipitation. RESULTS: Cells from the
      nasal septum can give rise to mature osteoblasts that express osteogenic markers
      (ALP, Runx2, Slug) and are able to mineralize. We demonstrated that Runx2, a
      transcription factor critical in early osteospecific differentiation, interacts
      in vivo with the promoter of the SLUG gene, a marker of osteoblast maturation.
      CONCLUSIONS: We demonstrated that nasal septum-derived osteoblasts represent an
      interesting alternative source for bone forming cells, and a promising material
      to be utilized in bone cellular therapy.

PMID- 21743869
TI  - Altered quality of life in Rendu-Osler-Weber disease related to recurrent
      epistaxis.
AB  - OBJECTIVES: Development and validation of an epistaxis-specific quality-of-life
      questionnaire (EQQoL) to evaluate the impact on quality of life of epistaxis,
      during hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: Prospective
      clinical study using QoL instruments administered twice in HHT patients. PATIENTS
      AND METHODS: In total, 109 patients who had epistaxis and a clinical diagnosis of
      HHT according to Curacao criteria were included. Invoice of the questionnaire in
      2004 and 2006 included SF-36, Jenkins' sleep scale and the new epistaxis
      specific13-item EQQoL. RESULTS: EQQoL uptake rate was 98%, mean score 58/100 +-
      27, and Cronbach alpha 0.96. EQQoL was sensitive to change with a strong
      correlation with the course of epistaxis. Factorial analysis showed that EQQoL
      was clearly distinct from SF-36 and Jenkins sleep scales. In stepwise
      multivariate ordinal logistic regression, frequency and duration of epistaxis
      were both associated with lower EQQoL. Conversely, visceral involvement and
      comorbidity had independent impact on SF-36 scores, but not on EQQoL.
      CONCLUSIONS: This new epistaxis-specific EQQoL questionnaire provides
      complementary information on the impact of HHT on patients quality of life
      relative to the SF-36 generic questionnaire. After international validation, the
      EQQoL might prove a useful tool for treatment evaluation.

PMID- 21743870
TI  - Psychosocial quality of life in hereditary haemorrhagic telangiectasia patients.
AB  - OBJECTIVES: The aim of this study was to evaluate psychosocial quality of life
      (PQoL) in patients with Hereditary Haemorrhagic Telangiectasia (HHT). STUDY
      DESIGN AND SETTING: A retrospective study was performed on PQoL in HHT patients
      presenting with epistaxis. One hundred fifteen patients were interviewed using a
      questionnaire designed by two sociologists and a head and neck surgeon. Changes
      over time were assessed according to information on psychosocial well-being,
      social life, family support, occupation, and medical and demographic data
      regarding age, gender and patient appearance. RESULTS: Analysis of Psychosocial
      Quality of Life (PQoL) revealed no statistical difference in relation to gender,
      marital status, household income or place of residence (rural or urban); however,
      a significant difference was observed with age. Elderly patients had a poorer
      PQoL than younger patients. Workers had a better PQoL than unemployed patients.
      Epistaxis and professional duties were correlated: workers with less than one
      episode of epistaxis per month were more active. Frequent episodes of epistaxis
      and abundant bleeding decreased PQoL. These patients felt different and often
      experienced a desire to withdraw compared to others. CONCLUSION: Epistaxis in
      hereditary haemorrhagic telangiectasia patients was associated with the
      impairment of many PQoL criteria, together with relationship modifications.

PMID- 21743871
TI  - IKK-2 inhibitor TPCA-1 represses nasal epithelial inflammation in vitro.
AB  - BACKGROUND: Nasal polyposis (NP) is considered a subgroup within chronic
      rhinosinusitis. NP can be further subdivided into aspirin sensitive- and aspirin
      tolerant types (ASNP/ ATNP). Although the true etiology of NP has not been
      identified so far, it is agreed that NP represents an inflammatory disease of the
      nasal mucosa. Alterations of cellular kinase activities including that of IKK-2
      might play a role in this inflammatory process. METHODS: Paraffin sections of
      ASNP, ATNP and controls were immunostained with Phospho-IkB-alpha antibody that
      detects the direct IKK-2 product (IkB-alpha. Intensity of epithelial staining was
      analysed semi-quantitatively by two independent observers. In cultured nasal
      polyp epithelial cells (NPECs) epithelial derived cytokines IL-8 and GRO alpha
      were induced by TNF-alpha or Staphylococcal supernatants and subsequently
      repressed by IKK-2 inhibitor TPCA-1. RESULTS: Significant Phospho-IkB-alpha
      staining was observed in the nasal epithelium of ASNP compared to ATNP and
      controls suggesting strong IKK-2 activation in patients with ASNP in vivo. In
      vitro, pro-inflammatory cytokines IL-8 and GRO-alpha in NPECs were significantly
      repressed by TPCA-1. CONCLUSION: IKK-2 activity is increased in the subgroup of
      ASNP. IL-8 and GRO-alpha responses were repressed by IKK-2 inhibitor TPCA-1 in
      vitro. IKK-2 inhibitors might represent a potential target for anti-inflammatory
      intervention in ASNP.

PMID- 21743872
TI  - Nasal lavage CCL24 levels correlate with eosinophils trafficking and symptoms in
      chronic sino-nasal eosinophilic inflammation.
AB  - OBJECTIVES: The aim of our study was to measure CCL24 (eotaxin-2) levels in nasal
      lavage fluid of patients with different forms of sinonasal chronic eosinophilic
      inflammation to verify the relationship with nasal hypereosinophilia and
      symptoms. METHODS: Patients with nasal hypereosinophilia were randomly recruited
      and grouped in persistent allergic rhinitis, non-allergic rhinitis with
      eosinophilia syndrome (NARES) and chronic rhinosinusitis with polyps. Non
      rhinitic volunteers were recruited as controls. CCL24 concentration was measured
      by 'Quantikine Human CCL24 Immunoassay'. Differential cell counts were performed
      by microscopic cytological examination of nasal tissue scraped by inferior
      turbinate. RESULTS: CCL24 levels measured in patient groups were significantly
      higher compared to control group with the highest levels in NARES patients.
      Eotaxin- 2 levels were significantly correlated to severity of symptoms and to
      the percentage of eosinophils in nasal tissue. CONCLUSIONS: We revealed high
      levels of CCL24 in all patient groups showing a significant correlation with the
      degree of eosinophilia and clinical symptoms. A prolonged accumulation of CCL24
      inside the nasal mucosa may sustain the process of unspecific self-perpetuating
      eosinophil recruitment pathognomonic of these patients.

PMID- 21743873
TI  - No evidence for a correlation of glutathione S-tranferase polymorphisms and
      chronic rhinosinusitis.
AB  - OBJECTIVE: Cellular detoxification mechanisms are mandatory for cellular
      protection against oxidative stress and reactive oxygen species. One major group
      of antioxidative active enzymes involved in cellular detoxification are the
      Glutathione S-Transferases (GST). Multiple subtypes like GSTM1, GSTP1, and GSTT1
      and variants of them are known, arising from allelic variations of the GST loci.
      Moreover, functional variants occur in high percentages and have been associated
      with diseases like bronchial asthma and bronchial hyperresponsiveness. The
      interplay of oxidative stress, detoxifying genes like GSTs and the genesis of
      respiratory tract illness is under contradictory debate. In this study, we
      analysed the potential association of GST-polymorphisms and chronic
      rhinosinusitis (CRS). METHODS: In total 170 nasal tissue samples, 49 tissue
      samples from patients with CRS without nasal polyps, 69 tissue samples from CRS
      with nasal polyps and 52 healthy tissue controls of the inferior turbinate were
      analysed for their individual GST-status. Genotypes for GSTM1 (null versus
      present), GSTT1 (null versus present), and GSTP1 (Ile105Val) were determined by
      Polymerase Chain Reaction. The respective genotypes were correlated to the
      incidence of CRS with and without nasal polyps in aspirin-tolerant and intolerant
      patients and to the individual health status concerning asthma and allergies.
      RESULTS: No correlation between any GST-polymorphism and CRS with and without
      nasal polyps or allergies or asthma or aspirin-intolerance was observed.
      CONCLUSION: Our results do not suggest that there is a relevant genetic
      predisposition considering the individual GST-status for the susceptibility of
      nasal respiratory epithelia leading to CRS.

PMID- 21743874
TI  - Nasal polyps do not contain olfactory structures.
AB  - BACKGROUND: Nasal polyposis can lead to olfactory dysfunction, either due to
      physical obstruction of the olfactory cleft or physiological disruption of the
      olfactory neuroepithelium. Where medical therapy has failed to relieve symptoms
      of nasal polyposis, surgical excision can be considered. However, removal of
      polyps medial to the middle turbinate is controversial: some believe this will
      relieve physical obstruction to odourants, others state that removal here risks
      excising olfactory neuroepithelium. METHODS: We stained 25 nasal polypectomy
      samples from the area medial to the middle turbinate with olfactory marker
      protein. RESULTS: We confirmed that our staining method worked on normal
      olfactory tissue. However, no positive staining of nasal polyps was demonstrated.
      CONCLUSION: We conclude that nasal polyps medial to the middle turbinate do not
      contain olfactory neurons, and surgical excision is not contraindicated.

PMID- 21743875
TI  - Estimating the effect of nasal steroid treatment on repeat polypectomies:
      survival time analysis using the General Practice Research Database.
AB  - BACKGROUND: Intranasal steroids are effective in preventing or delaying
      recurrence of nasal polyps. However, their effectiveness in delaying a need for
      repeat polypectomy in clinical practice is unknown. OBJECTIVES: To compare time
      to a repeat polypectomy between post-polypectomy intranasal steroid users and non
      users. METHODOLOGY/PRINCIPLE: Our cohort consisted of patients in GPRD who had
      undergone at least one nasal polypectomy procedure in or after the year 2000.
      These patients were followed for up to 4 years and the time to next polypectomy
      was estimated. Cox's proportional hazards regression was used to estimate the
      effect of post polypectomy intranasal steroid treatment on time to the next
      polypectomy after controlling for other respiratory conditions and their
      treatment. RESULTS: The cohort consisted of 1,675 patients with a mean age of 59
      years and 68% males. Of these, 576 patients were post-polypectomy steroid users
      and 1,099 patients were steroid non-users. The median time to repeat polypectomy
      was 812 days among the steroid users and 736 days among steroid non-users.
      Significantly less proportion of intranasal steroid users experienced a repeat
      polypectomy compared to steroid non-users. This difference was consistent among
      subgroups of females and concomitant rhinitis treatments users. Patients with
      post polypectomy intranasal steroid use showed lower risk for a repeat
      polypectomy compared to steroid non-users. Concomitant rhinitis medication users
      showed a higher risk whereas other confounders were not significant. CONCLUSIONS:
      Intranasal steroids were effective in delaying a repeat polypectomy. However,
      further research using a prospective design is necessary to quantify the benefit
      of ongoing steroid treatment.

PMID- 21743876
TI  - Long terms results of Draf type III (modified endoscopic Lothrop) frontal sinus
      drainage procedure in 122 patients: a single centre experience.
AB  - OBJECTIVES: To assess the effectiveness and factors associated with restenosis
      after Draf type III (Endoscopic Modified Lothrop) frontal sinus drainage
      procedure. DESIGN: Retrospective analysis of prospectively collected data.
      PATIENTS: A hundred and twenty two consecutive patients undergoing Draf III
      procedure for recalcitrant chronic frontal rhinosinusitis (CRS) (71%), frontal
      sinus mucocoele (15%), benign frontal sinus tumours (9%) and cystic fibrosis with
      severe CRS (5%) were followed up for an average of 33 months. OUTCOME MEASURES:
      Symptom burden (Visual Analogue Scale and Rhinosinusitis Outcome Measure),
      patency of neo-ostium and revision surgery. RESULTS: At the end of follow up,
      ninety percent of patients had a patent neo-ostium, while 88% were either
      clinically better or completely asymptomatic. Thirty-nine patients required
      endoscopic revision surgery and 9 eventually underwent frontal sinus
      obliteration. Sixty percent of revision operations were performed during the
      first two years. RSOM showed a significant improvement in both general and nasal
      symptoms while on a VAS, headache improved significantly. The only factor weakly
      associated with re-stenosis was the presence of allergy. There were no major
      complications during any of the procedures. CONCLUSION: Draf III Procedure is
      safe and effective for patients who have failed conventional frontal sinus
      procedures and a valid alternative to frontal sinus obliteration. Although the
      revision rate may appear to be quite significant, it can often be performed as an
      outpatient procedure and needs to be balanced against the reduced morbidity and
      the ease of follow-up.

PMID- 21743877
TI  - Isolated sphenoid inflammatory diseases associated with visual impairment: 15
      year experience at a single institution.
AB  - We present a retrospective series of 11 patients treated for isolated sphenoid
      inflammatory disease (ISID) with visual impairment in the period between 1994 and
      2008. The series included 7 females and 4 males. All patients, preoperatively
      assessed by CT or MR, underwent endoscopic sinus surgery and broad-spectrum
      antibiotic therapy. The procedure was always performed in an emergency setting,
      with an interval from the onset of visual impairment ranging between 1 and 40
      days (mean 9 days). The possibility of recovery was related to both the modality
      of onset and severity of the deficit. All patients with reduction of the visual
      field reported significant improvement after surgery. Patients with decreased
      visual acuity obtained partial or complete resolution, while in patients with
      preoperative blindness no improvement was observed. Moreover, no postoperative
      improvement was noticed in the case of severe deficits with sudden onset, whereas
      the treatment of mild deficits was successful even some weeks after their
      occurrence. In conclusion, although some factors may predict the likelihood of
      recovery, any patient with ISID associated with visual impairment should receive
      immediate medical and surgical treatment. Endoscopic surgery should be considered
      the technique of choice.

PMID- 21743878
TI  - Sinonasal inverted papilloma: 84 patients treated by endoscopy and proposal for a
      new classification.
AB  - AIM: To suggest a new classification system for sinonasal papilloma based on a
      critical analysis of surgical indications and results obtained. METHODS: We
      analysed surgical data from 84 cases of sinonasal papilloma treated
      endoscopically. RESULTS: In 58 males and 26 females, between 25 and 85 years, the
      ethmoid sinus (63 cases), the maxillary sinus (43), and the nasal fossa (22) were
      mostly involved. No case of endocranial extension or carcinoma was reported.
      Complications were reported in 15.4% of patients, as well as 5 recurrences
      (5.9%). Median follow up was 39,5 months. To categorise the tumour for the most
      appropriate surgical treatment, we propose a classification based on 6 main
      categories that depend on the location, origin and extension of the tumour.
      CONCLUSION: The classification that we propose presents advantages for prognosis
      and surgical indication in comparison with other classifications.

PMID- 21743879
TI  - Anti-estrogen therapy for hereditary hemorrhagic telangiectasia - a long-term
      clinical trial.
AB  - STATEMENT OF PROBLEM: Hereditary hemorrhagic telangiectasia (HHT) is associated
      with recurrent epistaxis in 90% of the cases. Good response to hormone treatment
      has been documented, although its use remains controversial. The aim of this
      study was to examine the efficacy of an anti-estrogenic agent, tamoxifen, in the
      treatment of HHT-associated epistaxis. METHOD OF STUDY: Out of 46 patients with
      diagnosis of epistaxis due to HHT who started treatment with tamoxifen 20 mg/d,
      38 patients completed a mean of 23.4 months of treatment. All patients filled out
      a self-assessment questionnaire of rhinologic Quality of Life and epistaxis
      grading scale. MAIN RESULTS: The bleeding score and the Quality of Life score
      improved. Hemoglobin concentration also improved. None of the patients needed
      blood transfusions during the treatment period. Only one patient had minor side
      effects of the drug. PRINCIPAL CONCLUSIONS: Tamoxifen appears to be an effective
      agent for the treatment of epistaxis due to HHT.

PMID- 21743880
TI  - Patient-reported olfactory function following endoscopic sinus surgery with
      modified endoscopic Lothrop procedure / Draf 3.
AB  - OBJECTIVES/HYPOTHESIS: The Modified Endoscopic Lothrop procedure (MELP) or Draf 3
      is a complex procedure, performed for chronic frontal sinusitis that is
      refractory to standard functional endoscopic sinus surgery. The procedure
      involves drilling of the frontal T (formed by the septum and middle turbinate's
      attachment to the skull base) onto the olfactory fossa often with exposure of the
      first olfactory neuron and may affect olfactory function. This study was
      performed to assess patients' subjective sense of smell following this procedure.
      STUDY DESIGN: Prospective study of retrospective data. METHODS: Sixty-eight
      patients, who underwent modified endoscopic Lothrop by the senior author (PJW)
      between 2003 and 2008, completed a post-operative questionnaire asking about
      their perception of olfactory function. All patients had their pre-operative
      subjective sense of smell documented prior to undergoing surgery. Patient records
      were reviewed for pertinent medical information such as the presence of asthma,
      aspirin sensitivity and nasal polyps. RESULTS: This study found that the majority
      of patients reported improvement in their sense of smell post-operatively, while
      only a small number reported a negative impact on their smell. Thirty-nine
      patients reported an improvement in their post-operative smell grade. Twenty
      patients reported no change in their smell grade, while the remaining 9 patients
      stated that their sense of smell worsened after surgery. No statistically
      significant correlation was found between patient outcome and the presence of
      asthma, nasal polyps, or Samter's triad. CONCLUSIONS: The Modified endoscopic
      Lothrop procedure/Draf 3 had a positive effect on subjective sense of smell post
      operatively in this cohort of patients.

PMID- 21743881
TI  - Olfactory bulb volume and olfactory function in patients with multiple sclerosis.
AB  - BACKGROUND: Some studies reported olfactory dysfunction in patients with multiple
      sclerosis (MS). There is no agreement about the most suitable testing method for
      measuring olfactory function (OF) in MS patients. Recent studies showed that
      olfactory bulb volume changes with the degree of olfactory dysfunction. We
      assessed olfactory bulb volume of MS patients with magnetic resonance imaging
      (MRI) and related it to the OF. MATERIAL AND METHODS: Volumetric measurements of
      the right and left olfactory bulb (OB) were performed by manual segmentation
      within 36 MS patients. Psychophysical testing of the orthonasal OF was performed
      using threshold-discrimination-identification (TDI) score in MS patients.
      RESULTS: Of all MS patients, 44.4% displayed olfactory dysfunction. The TDI score
      of all 36 MS patients, especially the score of the Identification subtest
      correlated strongly with neurological scores typical of MS. In patients with a
      decreased OB volume, there was a positive correlation between volumetry of the OB
      and OF. CONCLUSION: OB volumes may provide valuable information about MS patients
      with olfactory dysfunction. The TDI test and Identification subtest were very
      sensitive in detecting olfactory dysfunction in MS patients.

PMID- 21743882
TI  - Cross-cultural adaptation and validation of a quality of life questionnaire: the
      Nasal Obstruction Symptom Evaluation questionnaire.
AB  - BACKGROUND: The Nasal Obstruction Symptom Evaluation (NOSE) instrument is a
      disease-specific questionnaire for assessing the outcome of an intervention in
      nasal obstruction in trials. This instrument is only available in the English
      language and cross-culturally valid questionnaires are very important for all
      research, including nasal obstruction. The aim of the current study was to
      reproduce the cross-cultural adaptation process for the NOSE questionnaire in the
      Portuguese language (NOSE-p). METHODOLOGY/PRINCIPAL: Cross-cultural adaptation
      and validation of the instrument were divided into two stages. Stage 1 involved
      four bilingual professionals, an expert committee and the author of the original
      instrument. In Stage 2, the NOSE-p was tested on 33 patients undergoing
      septoplasty for internal consistency, test-retest reliability, construct
      validity, discriminant validity, criterion validity, and response sensitivity.
      RESULTS: The cross-cultural adaptation process was completed and the NOSE-p was
      demonstrated to be a valid instrument with satisfactory construct validity. It
      showed an adequate internal consistency reliability and adequate test-retest
      reliability. It could discriminate between patients with and without nasal
      obstruction and it has a high response sensitivity to change. CONCLUSIONS: The
      cross-cultural adaptation and validation process demonstrated to be valid and the
      NOSE-p proved to be applicable in Brazil.

PMID- 21743883
TI  - Effect of CPAP-therapy on bronchial and nasal inflammation in patients affected
      by obstructive sleep apnea syndrome.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been shown to be
      associated to upper and lower airways inflammation. Continuous positive airway
      pressure (CPAP) is the elective treatment of OSAS. The aim of the present study
      was to assess the effect of CPAP-therapy on airway and nasal inflammation.
      METHODS: In 13 non-smoking subjects affected by untreated OSAS and in 11 non
      smoking normal volunteers, airway inflammation was detected by analyses of the
      induced sputum. In the OSAS group measurements were repeated after 1, 10 and 60
      days of the appropriate CPAP treatment. In addition, in 12 subjects of the OSAS
      group, nasal inflammation was detected by the analysis of induced nasal
      secretions at baseline, and after 1, 10 and 60 days of CPAP treatment. RESULTS:
      OSAS patients, compared to normal controls, showed at baseline a higher
      percentage of neutrophils and a lower percentage of macrophages in the induced
      sputum. One, 10 and 60 days of appropriate CPAP-therapy did not change the
      cellular profile of the induced sputum. In addition, in the OSAS patients, the
      high neutrophilic nasal inflammation present under baseline conditions was not
      significantly modified by CPAP-therapy. Finally, no patients developed airway
      hyper-responsiveness after CPAP therapy. CONCLUSIONS: In OSAS subjects, the
      appropriate CPAP-therapy, while correcting the oxygen desaturation, does not
      modify the bronchial and nasal inflammatory profile.

PMID- 21743884
TI  - The significance of rhinomanometry in evaluation of postlaryngectomy olfactory
      rehabilitation by polite yawning technique.
AB  - OBJECTIVE: To corroborate the result of postlaryngectomy olfactory rehabilitation
      evaluating the efficacy of the Polite Yawning Technique (PYT) with rhinomanometry
      and odours with the Smell diskettes Olfaction test (SDOT). MATERIALS AND METHODS:
      Thirty-two laryngectomised patients were subjected to olfactory rehabilitation
      consisting of 15-minute training and independent exercising for two weeks. The
      sense of smell and nasal airflow in laryngectomised patients were examined before
      and after implementation of PYT. RESULTS: The differences in SDOT results prior
      to and after introduction of PYT were statistically significant, most patients
      achieving better results after rehabilitation. A significant positive correlation
      was obtained in results of SDOT and rhinomanometry prior to and after
      introduction of PYT. The results of measurements after rehabilitation showed that
      75% of patients had improved nasal breathing, 78% of patients had a better sense
      of smell and 40% of patients became normosmic. CONCLUSIONS: PYT has proved to be
      an effective method in olfaction rehabilitation following total laryngectomy.
      Using rhinomanometry, evaluation of the rehabilitation success is substantiated
      while the technique is simplified.

PMID- 21743885
TI  - Reference values for acoustic rhinometry in children at baseline and after
      decongestion.
AB  - BACKGROUND: Acoustic rhinometry is widely used for objective evaluation of nasal
      dimensions. However, there is a lack of agreement on the normative values in
      children at baseline, and especially after decongestion. The purpose of this
      study was to determine the reference values for Finnish school children for
      acoustic rhinometry in non-decongested and decongested noses, and to find out
      which of the potential predictors (age, sex, body surface area (BSA) and height)
      would be the most useful one(s). METHODOLOGY: The study included 124 children
      aged between 6.90 and 13.84 years with no permanent nasal symptoms. RESULTS: At
      baseline, the mean total minimal cross-sectional area (MCA) was 0.752 cm2, and
      the mean total volume between 0 - 3 cm (VOL) was 4.00 cm3. After decongestion,
      the total MCA was 0.794 cm2, and the VOL was 4.38 cm3. There was a significant
      correlation between MCA and age, between VOL and height, and between VOL and BSA
      at baseline and after decongestion. We found no difference in the values between
      boys and girls. CONCLUSIONS: We conclude that acoustic rhinometry is a suitable
      objective method to monitor the changes in mucosal swelling and nasal obstruction
      in children. Age and height or BSA of a child can be suggested as predictive
      factors.

PMID- 21743886
TI  - Radiological examinations of the anatomy of the inferior turbinate using digital
      volume tomography (DVT).
AB  - BACKGROUND: Since the last 120 years there were only few descriptions of the
      anatomical sizes of the inferior turbinate in the literature. On this background
      the current study should evaluate the radiological dimensions of the inferior
      turbinate and the septum using DVT. METHODS: The latest generation of the Accu-I
      tomo was used. The data of 100 adult patients have been evaluated. RESULTS: The
      bony length was found to be 38.9 mm, the mucosal length 51.0 mm. The findings of
      the total mucosal thickness at different measuring points were between 8.1 mm and
      10.9 mm, those of the bony thickness were between 0.9 mm and 2.3 mm and those of
      the bony height were between 3.9 mm and 20.8 mm. CONCLUSION: The results of this
      radiological study are able to point out the importance of preoperative
      anatomical evaluation of radiological images. The preoperative focus on the
      individual anatomy is very important because of the choice of an adequate
      surgical treatment. Today new radiological techniques can help to find out
      whether the reason for hypertrophied turbinates is caused by bone, mucosa or
      both. This knowledge enables a concerted treatment concept.

PMID- 21743887
TI  - Novel borothermal process for the synthesis of nanocrystalline oxides and borides
      of niobium.
AB  - A new process has been developed for the synthesis of nanocrystalline niobium
      oxide and niobium diboride using an amorphous niobium precursor obtained via the
      solvothermal route. On varying the ratio of niobium precursor to boron and the
      reaction conditions, pure phases of nanostructured niobium oxides (Nb(2)O(5),
      NbO(2)), niobium diboride (NbB(2)) and core-shell nanostructures of
      NbB(2)@Nb(2)O(5) could be obtained at normal pressure and low temperature of 1300
      degrees C compared to a temperature of 1650  degrees C normally used. The above
      borothermal process involves the in situ generation of B(2)O(2) to yield either
      oxide or diboride. The niobium oxides and borides have been characterized in
      detail by XRD, HRTEM and EDX studies. The core-shell structure has been
      investigated by XPS depth profiling, EFTEM and EELS (especially to characterize
      the presence of boron and the shell thickness). The niobium diboride nanorods
      (with high aspect ratio) show a superconducting transition with the T(c) of 6.4
      K. In the core-shell of NbB(2)@Nb(2)O(5), the superconductivity of NbB(2) is
      masked by the niobium oxide shell and hence no superconductivity was observed.
      The above methodology has the benefits of realizing both oxides and borides of
      niobium in nanocrystalline form, in high purity and at much lower temperatures.

PMID- 21743888
TI  - A molecular bowl sumanene.
AB  - Nonplanar polyaromatic carbon molecules including fullerenes and carbon nanotubes
      have been attracting great interest due to their potential as materials,
      catalysts, etc. In this context, bowl-shaped polyaromatic hydrocarbons (pi bowls)
      are considered to be key materials in the science of nonplanar pi-conjugated
      carbon systems. Among pi bowls, we focused on a molecular bowl "sumanene
      (C(21)H(12))" featuring a C(3v) symmetric structural motif present in fullerenes
      or carbon nanotube molecules. In this article, we present the research on
      sumanenes to date, including their synthesis, structural characterization,
      derivatization, complexation, and their potential uses as electrical materials.
      The characteristic structural feature of a sumanene depends on three sp(3)
      hybridized carbon atoms at the benzylic positions. Facile functionalization via
      selective formation of benzylic anions gives stereoselective substituted
      compounds, the pi-extended derivatives, and the deeper pi bowls. Furthermore, the
      dynamically flexible aspect based on bowl-to-bowl inversion is also described.
      The crystal with a columnar bowl-in-bowl stacking exhibits a high electron
      transport ability with anisotropy. Complexation with a cyclopentadienyl iron
      cation results in the first selective formation of the concave-bound complex as a
      pi-bowl complex.

PMID- 21743889
TI  - Water-assisted assembly of (E)-arylvinylpyridine hydrochlorides: effective
      substrates for solid-state [2+2] photodimerization.
AB  - Water molecules assist the assembly of (E)-arylvinylpyridine hydrochlorides in a
      head-to-tail and face-to-face fashion by way of N-HO hydrogen bonds in
      combination with cation-pi interactions between the pyridinium and aromatic
      rings. Photolysis of the pyridinium salt hydrates provided synHT dimers in high
      yields.

PMID- 21743890
TI  - Synthesis and photo- and electroluminescence properties of 3,6-disubstituted
      phenanthrenes: alternative host material for blue fluorophores.
AB  - Three deep-blue fluorescent 9,10-bis(4-tert-butylphenyl)phenanthrenes with
      diphenyl, -naphthyl, and -pyrenyl moieties at C3 and C6 positions were
      synthesized and used as the host for doped blue fluorescent devices; one of these
      devices reveals excellent external quantum efficiency of 7.7% and current
      efficiency of 9.8 cd A(-1) with low efficiency roll-off, deep-blue color
      coordinates (0.14, 0.14) and long operational lifetime.

PMID- 21743891
TI  - The synthesis of dehydrotryptophan and dehydrotryptophan-containing peptides.
AB  - Dehydrotryptophan and its derivatives are non-proteinogenic amino acids commonly
      found in peptide-based natural products produced by microorganisms, marine
      organisms and plants. These non-proteinogenic amino acids are found in secondary
      metabolites and are formed by post translational modification processes. Although
      comprehensive reviews on the synthesis of dehydroamino acids are available, this
      perspective focuses solely on methods to synthesise the dehydrotryptophan
      containing segment of naturally occurring peptides, amino acids and their
      derivatives.

PMID- 21743892
TI  - LDL-based nanoparticles for contrast enhanced MRI of atheroplaques in mouse
      models.
AB  - A LDL particle functionalized with a GdDO3A-monoamide chelate with a long alkenyl
      anchor (GdDO3A-OA) was prepared for in vivo detection of atheroplaques. The
      GdDO3A-OA, when successfully intercalated into the lipid layer of LDL particles,
      led to a significant enhancement of magnetic resonance imaging signal intensity
      of atheroplaques in atherosclerosis mouse models.

PMID- 21743893
TI  - Cavitand supported tetraphosphine: cyclodextrin offers a useful platform for
      Suzuki-Miyaura cross-coupling.
AB  - The cyclodextrin-tetraphosphine hybrid coined alpha-Cytep allows turnover numbers
      up to 340,000,000,000 and turnover frequencies up to 1,000,000,000 h(-1) to be
      reached in Suzuki-Miyaura reactions. These exceptional figures are clearly linked
      to the outstanding longevity of the reactive species induced by the ligand alpha
      Cytep and illustrates the rising potential of cyclodextrins in catalytic
      applications.

PMID- 21743894
TI  - A simple strategy for charge selective biopolymer sensing.
AB  - Polysaccharide-induced protein fluorescence 'turn-on' responses have been studied
      in the presence of similarly charged micelle at pH ~3. Quenched protein
      fluorescence is selectively recovered ('on' state) for bovine serum albumin (BSA)
      with sodium carboxy methyl cellulose (SCMC) and for pepsin (PS) with chitosan
      (CS) with starting ultra low concentrations of 0.04 MUM and 0.008 MUM
      respectively.

PMID- 21743895
TI  - The influence of acidities of boron- and aluminium-containing MFI zeolites on co
      reaction of methanol and ethene.
AB  - A series of boron- and aluminium-containing MFI zeolites were synthesized and
      various characterization techniques, such as NMR ((27)Al, (29)Si and (11)B), were
      employed to study the acidities of zeolites. Moreover, in situ IR was applied to
      investigate the interaction of methanol and ethene with the acid sites, and those
      catalytic materials were used for co-reaction of methanol and ethene to produce
      propene. The production of propene was related to the Al content of the zeolites
      with Si/Al ratios of higher than 90. It is implied that the presence of boron
      during the synthesis directed the aluminium to occupy certain tetrahedral sites
      in the zeolite framework, thus preventing the formation of ethene oligomers, and
      resulting in increased propene selectivity.

PMID- 21743896
TI  - Structure and properties of the (HCl)2H2O cluster observed by chirped-pulse
      Fourier transform microwave spectroscopy.
AB  - The rotational spectrum of the cyclic (HCl)(2)H(2)O cluster has been identified
      for the first time in the chirped pulse, Fourier transform microwave spectrum of
      a supersonically expanded HCl/H(2)O/Ar mixture. The spectrum was measured at
      frequencies 6-18.5 GHz, and transitions in two inversion-tunneling states, at
      close to 1 : 3 relative intensity, have been assigned for the parent species. The
      two single (37)Cl isotopic species, and the double (37)Cl species have been
      assigned in the natural abundance sample, and the (18)O and HDO species of the
      cluster were identified in isotopically enriched samples. The rich nuclear
      quadrupole hyperfine structure due to the presence of two chlorine nuclei has
      been satisfactorily fitted and provided useful information on the nonlinearity of
      intermolecular bonds in the cluster. The r(s) heavy atom geometry of the cluster
      was determined and the strongest bond in the intermolecular cycle r(O...HCl) =
      3.126(3) A, is found to be intermediate in length between the values in
      H(2)O...HCl and (H(2)O)(2)HCl. The fitted spectroscopic constants and derived
      molecular properties are compared with ab initio predictions, and a discussion of
      complexation effects in these three clusters is made.

PMID- 21743897
TI  - Intramolecular OH...pi interactions in alkenols and alkynols.
AB  - The vibrational overtone spectra of propargyl alcohol (prop-2-yn-1-ol, PA), allyl
      alcohol (prop-2-en-1-ol, AA), propargyl carbinol (but-3-yn-1-ol, PC) and allyl
      carbinol (but-3-en-1-ol, AC) were recorded with intracavity laser photoacoustic
      spectroscopy (ICL-PAS) in the Deltav(OH) = 3, 4 and 5 regions for propargyl
      alcohol and allyl alcohol and in the Deltav(OH) = 4 and 5 regions for propargyl
      carbinol and allyl carbinol. Local mode anharmonic oscillator calculations were
      performed with explicitly correlated coupled cluster methods to guide spectral
      assignment. Atoms in molecules (AIM) and non-covalent interactions (NCI)
      calculations were carried out to analyze the interactions between the OH-group
      and the pi-electrons of the carbon-carbon multiple bonds. We ascertain the effect
      of the carbon chain length and saturation on the conformation and spectroscopy of
      the four alcohols in relation to intramolecular hydrogen bonding interactions.

PMID- 21743898
TI  - A rapid and facile method for the general synthesis of 3-aryl substituted 4,5,6,7
      tetrahydro[1,2,3]triazolo[1,5-a]pyrazines and their ring fused analogues.
AB  - We report a general and facile method that provides rapid entry into 3-aryl
      substituted 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines and their ring
      fused analogues in one-pot under palladium-copper catalysis. The methodology
      utilises simple and easily available substrates of broad range. The applicability
      of this reaction for the synthesis of optically active products has been
      demonstrated. A plausible reaction mechanism has also been proposed.

PMID- 21743899
TI  - Theoretical studies on the mechanism and stereoselectivity of Rh(Phebox)
      catalyzed asymmetric reductive aldol reaction.
AB  - Density functional theory calculations (B3LYP) have been carried out to
      understand the mechanism and stereochemistry of an asymmetric reductive aldol
      reaction of benzaldehyde and tert-butyl acrylate with hydrosilanes catalyzed by
      Rh(Phebox-ip)(OAc)(2)(OH(2)). According to the calculations, the reaction
      proceeds via five steps: (1) oxidative addition of hydrosilane, (2) hydride
      migration to carbon-carbon double bond of tert-butyl acrylate, which determines
      the chirality at C2, (3) tautomerization from rhodium bound C-enolate to rhodium
      bound O-enolate, (4) intramolecular aldol reaction, which determines the
      chirality at C3 and consequently the anti/syn-selectivity, and (5) reductive
      elimination to release aldol product. The hydride migration is the rate
      determining step with a calculated activation energy of 23.3 kcal mol(-1). In
      good agreement with experimental results, the formation of anti-aldolates is
      found to be the most favorable pathway. The observed Si-facial selectivity in
      both hydride migration and aldol reaction are well-rationalized by analyzing
      crucial transition structures. The Re-facial attack transition state is
      disfavored because of steric hindrance between the isopropyl group of the
      catalyst and the tert-butyl acrylate.

PMID- 21743904
TI  - Determination of the equilibrium formation constants of two U(VI)-peroxide
      complexes at alkaline pH.
AB  - The formation of uranyl-peroxide complexes was studied at alkaline media by using
      UV-Visible spectrophotometry and the STAR code. Two different complexes were
      found at a H(2)O(2)/U(VI) ratio lower than 2. A graphical method was used in
      order to obtain the formation constants of such complexes and the STAR program
      was used to refine the formation constants values because of its capacity to
      treat multiwavelength absorbance data and refining equilibrium constants. The
      values obtained for the two complexes identified were: UO(2)(2+) + H(2)O(2) +
      4OH(-) <-> UO(2)(O(2))(OH)(2)(2-) + 2H(2)O: log beta degrees (1,1,4) = 28.1 +/-
      0.1 (1). UO(2)(2+) + 2H(2)O(2) + 6OH(-) <-> UO(2)(O(2))(2)(OH)(2)(4-) + 4H(2)O:
      log beta degrees (1,2,6) = 36.8 +/- 0.2 (2). At hydrogen peroxide concentrations
      higher than 10(-5) mol dm(-3), and in the absence of carbonate, the
      UO(2)(O(2))(2)(OH)(2)(4-) complex is predominant in solution, indicating the
      significant peroxide affinity of peroxide ions for uranium and the strong
      complexes of uranium(VI) with peroxide.

PMID- 21743905
TI  - Highly selective ion probe for Al3+ based on Au(I)...Au(I) interactions in a bis
      alkynyl calix[4]arene Au(I) isocyanide scaffold.
AB  - A bis-alkynyl calix[4]arene Au(I) isocyanide complex has been synthesized and
      demonstrated to be a selective ion probe for Al(3+) based on Au(I)Au(I)
      interactions.

PMID- 21743906
TI  - New perovskite materials of the La(2-x)Sr(x)CoTiO6 series.
AB  - Substitution of La(3+) by Sr(2+) in the double perovskite La(2)CoTiO(6) yields
      materials of the La(2-x)Sr(x)CoTiO(6) series showing a significant amount of
      trivalent cobalt ions when prepared at ambient atmosphere. The as-prepared
      compounds can be reduced in severe conditions retaining the perovskite structure
      while inducing the formation of a large amount of oxygen vacancies. The limit of
      aliovalent substitution in this series was found to extend up to x = 1. For
      substitution of La(3+) up to 15% cobalt and titanium are ordered, though the
      order is progressively lost as x increases; for x>= 0.30 no ordering is observed
      as evidenced by magnetic measurements. The ability of these materials to present
      either cobalt ions in a mixed oxidation state or large amounts of anion vacancies
      depending on the atmosphere makes them interesting to be further investigated
      regarding their electrical and electrochemical properties, and hence, their
      usefulness in some electrochemical devices.

PMID- 21743907
TI  - Expanding the 3d-4f heterometallic chemistry of the (py)2CO and pyCOpyCOpy
      ligands: structural, magnetic and Mossbauer spectroscopic studies of two Fe(II)
      Gd(III) complexes.
AB  - Complex [Fe(II)Gd(III){pyCO(OEt)pyCOH(OEt)py}(3)](ClO(4))(2) (1) crystallizes in
      the Cc space group and contains one hexacoordinate ferrous ion and one
      enneacoordinate Gd(III) ion. Complex
      [Fe(2)(II)Gd(III){pyCO(OEt)py}(4)(NO(3))(H(2)O)][Gd(NO(3))(5)](0.5)(ClO(4)) (2)
      crystallizes in the C2/c space group and contains two hexacoordinate ferrous ions
      and one octacoordinate Gd(III) ion. Both complexes have been prepared by the
      metal-assisted ethanolysis of ligands di-2,6-(2-pyridylcarbonyl)pyridine
      (pyCOpyCOpy, dpcp) and di-2-pyridyl ketone ((py)(2)CO, dpk), which exhibit
      similar structures. Mossbauer spectroscopic studies of 2 revealed the presence of
      two quadrupole-split doublets of equal intensities, each assigned to a ferrous
      site. These doublets exhibit similar isomer shifts (delta(1) = 1.14 mm s(-1),
      delta(2) = 1.11 mm s(-1)) but quite different quadrupole splittings (DeltaE(Q1) =
      3.55 mm s(-1), DeltaE(Q2) = 2.74 mm s(-1)). Magnetic studies revealed weak
      ferromagnetic Fe(II)-Gd(III) interactions for both complexes (J(FeGd) = +0.68 cm(
      1), D(Fe) = 12.0 cm(-1) for 1 and J(FeGd) = +0.03 cm(-1), J(FeFe) = -1.73 cm(-1)
      for 2, according to the -JS(i)S(j) spin-Hamiltonian formalism).

PMID- 21743908
TI  - Isocyanide insertion and cyclization reactions to form indolines using pincer
      type complexes of scandium.
AB  - The addition of 2,6-dimethylphenyl isocyanide (CN[DMeP], two equivalents) to
      previously reported (PNP)Sc(III) pyridyl complexes resulted in the formation of
      novel indoline complexes of scandium. By varying the nature of the pyridyl moiety
      one can intercept an intermediate prior to methyl migration. In addition to
      structural studies of two indolene complexes, we also propose a mechanism for the
      insertion and indolene ring closure.

PMID- 21743909
TI  - Evolution of orientation degree, lattice dynamics and electronic band structure
      properties in nanocrystalline lanthanum-doped bismuth titanate ferroelectric
      films by chemical solution deposition.
AB  - Ferroelectric lanthanum (La)-substituted bismuth titanate (Bi(4
      x)La(x)Ti(3)O(12), BLT) nanocrystalline films with the composition range of 0
      <=x<= 1 have been directly deposited on n-type Si (100) substrates by chemical
      solution deposition. The La substitution effects on the preferred orientation,
      surface morphology, phonon modes, emission bands and electronic band structures
      of the BLT films have been investigated by microscopy, Raman scattering,
      photoluminescence and spectroscopic ellipsometry at room temperature. X-Ray
      diffraction analysis shows that the films are polycrystalline and exhibit the
      pure perovskite phase structure. With increasing La composition, the (100)
      orientation degree can be enhanced and the root-mean-square roughnesses slightly
      increase from 6.5 to 8.3 nm. It was found that the Raman-active mode A(1g)[Bi] at
      about 59 cm(-1) is unchanged while the B(1g) and A(1g)[Ti] phonon modes at about
      648 and 853 cm(-1) are shifted towards higher frequency by about 36.6 and 8.4 cm(
      1), respectively. Photoluminescence spectra show that the intensity of the peak
      located at about 2.3 eV increases with the La composition, except for the
      Bi(3)LaTi(3)O(12) film, due to the smallest grain size and oxygen vacancy
      defects. The optical constants of the BLT films have been uniquely extracted by
      fitting the measured ellipsometric spectra with a four-phase layered model
      (air/surface rough layer/BLT/Si) in the photon energy range of 0.73-4.77 eV. The
      Adachi dielectric function model has been successfully applied and reasonably
      describes the optical response behavior of the ferroelectric BLT films. Moreover,
      the film packing density decreases while the optical band gap linearly increases
      from 3.610 +/- 0.066 to 3.758 +/- 0.068 eV with increasing La composition. It is
      surmised that the phenomena are mainly ascribed to the variations of the
      electronic structure, especially for the conduction band, which is perturbed by
      the La doping.

PMID- 21743910
TI  - Titanium arsenide films from the atmospheric pressure chemical vapour deposition
      of tetrakisdimethylamidotitanium and tert-butylarsine.
AB  - Thin films of titanium arsenide have been deposited from the atmospheric pressure
      chemical vapour deposition (APCVD) of [Ti(NMe(2))(4)] and (t)BuAsH(2) at
      substrate temperatures between 350-550  degrees C. Highly reflective, silver
      coloured films were obtained which showed borderline metallic-semiconductor
      resistivities. The titanium arsenide films were analyzed by scanning electron
      microscopy (SEM), Raman spectroscopy, wavelength dispersive analysis of X-rays
      (WDX), powder X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS).
      The films showed variable titanium to arsenic ratios but at substrate
      temperatures of 500 and 550  degrees C films with a 1 : 1 ratio of Ti : As,
      consistent with the composition TiAs, were deposited. Powder XRD showed that all
      of the films were crystalline and consistent with the formation of TiAs. Both
      nitrogen and carbon contamination of the films were negligible.

PMID- 21743911
TI  - Polythiol binding to biologically relevant metal ions.
AB  - The coordination properties of three peptides with CXXC motif: Ac-GCASCDNCRACKK
      NH(2), Ac-GCASCDNCRAAKK-NH(2) and Ac-GCASCDNARAAKK-NH(2) as donors of four, three
      and two thiol ligands for Ni(2+),Cd(2+), Zn(2+) and Bi(3+) were studied by
      potentiometric titrations, UV-Vis and CD spectra measurements. Since the
      stability of the complexes is closely connected with the amount of the metal
      bound cysteine sulfurs, competition plots of the complexes of peptides with 2, 3
      and 4 cysteines further prove the involvement of all thiols in the metal ion
      binding. Furthermore, the sulfur-bound zinc complexes appear to be much more
      stable than the sulfur-bound nickel ones. The stabilities of the studied
      complexes decreases in the series Bi(3+) ? Cd(2+) > Zn(2+) > Ni(2+).

PMID- 21743912
TI  - Observation of slow magnetic relaxation in triple-stranded lanthanide helicates.
AB  - Two dinuclear triple-stranded helicates [Ln(2)L(3)](3+) (Ln = Dy and Tb) obtained
      via self-assembly from the ligand HL (2,6-diformyl-4-methylphenol
      di(benzoylhydrazone)) and lanthanide perchlorate have been synthesized and
      characterized. The crystal structural analysis demonstrates that three ligand
      strands wrap around a pseudo-threefold axis defined by the two metal ions,
      leading to a 'meso'-relation between the right- (Delta) and left-hand (Lambda)
      configurations of [Ln(2)L(3)](3+) in the crystal. Each Ln(III) ion is coordinated
      by nine donor atoms in a distorted tricapped trigonal-prismatic arrangement.
      Alternating current (ac) susceptibility measurements of [Dy(2)L(3)](3+) reveal a
      frequency-dependent out-of-phase signal under a 700 Oe dc field, indicating the
      onset of the slow relaxation of magnetization with a roughly estimated activation
      energy of ~5 K and tau(0) of 10(-7) s.

PMID- 21743913
TI  - A neutron reflection study of surface enrichment in nematic liquid crystals.
AB  - The interfacial adsorption properties of several different dopants in
      cyanobiphenyl liquid crystals have been measured using specular neutron
      reflection. It was found that a partly fluorinated analogue of 11OCB, called F17,
      adsorbed strongly at the interface between 5CB and air but it was not adsorbed at
      the interface between 5CB and a solid substrate treated with cetyl trimethyl
      ammonium bromide (CTAB). The concentration dependence of the adsorption at the
      air interface was well described by the Brunauer, Emmett and Teller (BET) model,
      adapted for solutions rather than the gas phase. The isotherms are determined by
      two equilibrium constants: K(S) for adsorption of the dopant directly at the
      interface and K(L) for adsorption onto previously adsorbed dopant. The
      temperature dependence of K(S) indicated that the adsorption enthalpy is not
      influenced by the phase of the 5CB and its value of -29 kJmol(-1) is consistent
      with physical adsorption. The value of K(L) is zero in the isotropic phase but
      increases rapidly on cooling in the nematic phase suggesting that the F17 is less
      compatible with nematic than isotropic 5CB. The smallest layer thicknesses (~18
      A) suggest that the F17 molecules are approximately perpendicular to the surface.
      The other dopants studied were components of the E7 mixture: 8OCB and 5CT. No
      adsorption was found for 8OCB but 5CT showed adsorption at a CTAB treated solid
      interface when present in 5CB at the 10% level. In this case, the value of K(S)
      was much smaller than for F17 but the value of K(L) was such that an exponential
      concentration profile (predicted by the BET model) was observed with
      characteristic thickness of ~200 A. The results demonstrate the potential for
      very precise control of surface properties in liquid crystal devices by using
      appropriate dopants.

PMID- 21743914
TI  - Intrinsic UV absorption spectrometry observed with a liquid core waveguide as a
      sensor technique for monitoring ozone in water.
AB  - The industrial use of ozone as a sanitizing agent in water treatment and food
      processing in recent years calls for sensor technologies for monitoring ozone in
      water for process control. Ozone molecules absorb UV light with a peak absorption
      wavelength at 254 nm. This property has been used in this work to develop a
      simple sensor technology for online, real-time continuous monitoring of trace
      ozone in water. A Teflon AF2400 tube filled with pure water forms a liquid core
      waveguide (LCW), which is used as a long-path-length optical absorption cell.
      This pure water filled tube was deployed into a water sample. Ozone molecules
      dissolved in the water sample permeate through the Teflon AF2400 tube wall and
      dissolve in water filled in the tube. This prevents interference species from
      entering the LCW, and eliminates interferences. The optical absorption signal of
      the long-path-length cell at 254 nm measured by guiding light through the LCW is
      used as a sensing signal. This simple structured sensor does not involve any
      chemical reagent, is reversible, and has a response time <4.5 minutes. It can be
      used to detect ozone in water samples down to 3.6 * 10(-9) mol L(-1).

PMID- 21743915
TI  - Multiplexed analysis of silver(I) and mercury(II) ions using oligonucletide-metal
      nanoparticle conjugates.
AB  - A colorimetric assay has been developed for the simultaneous selective detection
      of silver(I) and mercury(II) ions utilizing metal nanoparticles (NPs) as sensing
      element based on their unique surface plasmon resonance properties. In this
      method, sulfhydryl group modified cytosine-(C)-rich ssDNA (SH-C-ssDNA) was self
      assembled on gold nanoparticles (AuNPs) to produce the AuNPs-C-ssDNA complex, and
      sulfhydryl group modified thymine-(T)-rich ssDNA (SH-T-ssDNA) was self-assembled
      on silver nanoparticles (AgNPs) to produce the AgNPs-T-ssDNA complex.
      Oligonucleotides (SH-C-ssDNA or SH-T-ssDNA) could enhance the AuNPs or AgNPs
      against salt-induced aggregation. However, the presence of silver(I) ions (Ag(+))
      in the complex of ssDNA-AuNPs would reduce the stability of AuNPs due to the
      formation of Ag(+) mediated C-Ag(+)-C base pairs accompanied with the AuNPs color
      change from red to purple or even to dark blue. Moreover, the presence of
      mercury(II) ions (Hg(2+)) would also reduce the stability of AgNPs due to the
      formation of Hg(2+) mediated T-Hg(2+)-T base pairs accompanied with the AgNPs
      color change from yellow to brown, then to dark purple. The presence of both
      Ag(+) and Hg(2+) will reduce the stability of both AuNPs and AgNPs and cause the
      visible color change. As a result, Ag(+) and Hg(2+) could be detected
      qualitatively and quantitatively by the naked eye or by UV-vis spectral
      measurement. The lowest detectable concentration of a 5 nM mixture of Ag(+) and
      Hg(2+) in the river water was gotten by the UV-vis spectral measurement.

PMID- 21743916
TI  - SE(R)RS devices fabricated by a laser electrodispersion method.
AB  - A novel laser electrodispersion (LE) technique was employed to deposit gold
      nanoparticles onto Si and SiO(x) surfaces. The LE technique combines laser
      ablation with cascade fission of liquid metal micro-drops, which results in the
      formation of nanoparticles upon rapid cooling. The shape and the size
      distribution of the Au nanoparticles prepared by LE depend on the nature of the
      support. Gold nanoparticles were also deposited in the channels of microreactors
      fabricated by wet etching of Si and used as SE(R)RS sensors. The influence of the
      nanoparticle surface density as well as of the nature of the substrate on the
      Raman response was studied. At an appropriate surface density of the deposited
      nanoparticles a significant enhancement of Raman signal was observed showing the
      possibility to create efficient SERS substrates. Application of microfluidic
      devices in surface enhanced Raman spectroscopy (SERS) in continuous-flow mode
      with sensor regeneration is described.

PMID- 21743917
TI  - Sweet (hetero)aromatics: glycosylated templates for the construction of
      saccharide mimetics.
AB  - Mono- and diglycosylated aromatics and heteroaromatics may serve as building
      blocks for the construction of metabolically stable mimetics of oligosaccharides.
      Methods for their preparation from monosaccharidic precursors by direct C
      glycosylation, dipolar cycloaddition or Larock cyclization are described.

PMID- 21743918
TI  - Combined in situ XRD and in situ XANES studies on the reduction behavior of a
      rhenium promoted cobalt catalyst.
AB  - A 10% Co-4% Re/(2% Zr/SiO(2)) catalyst was prepared by co-impregnation using a
      silica support modified by 2% Zr. The catalyst was characterized by temperature
      programmed reduction (TPR), in situ XRD and in situ XANES analysis where it was
      simultaneously exposed to H(2) using a temperature programmed ramp. The results
      showed the two step reduction of large crystalline Co(3)O(4) with CoO as an
      intermediate. TPR results showed that the reduction of highly dispersed Co(3)O(4)
      was facilitated by reduced rhenium by a H(2)-spillover mechanism. In situ XRD
      results showed the presence of both, Co-hcp and Co-fcc phases in the reduced
      catalyst at 400  degrees C. However, the Co-hcp phase was more abundant, which is
      thought to be the more active phase as compared to the Co-fcc phase for CO
      hydrogenation. CO hydrogenation at 270  degrees C and 5 bar pressure produces no
      detectable change in the phases during the time of experiment. In situ XANES
      results showed a decrease in the metallic cobalt in the presence of H(2)/CO,
      which can be attributed due to oxidation of the catalyst by reaction under these
      conditions.

PMID- 21743919
TI  - Energy alignment and surface dipoles of rylene dyes adsorbed to TiO2
      nanoparticles.
AB  - The energy loss in dye-sensitized solar cells calculated from the energy
      difference between the lowest electronic transition of the dye and the obtained
      open-circuit voltage is often 1 eV or even more. To minimize this loss, it is
      important to accurately determine the energy alignment at the TiO(2)/dye/redox
      mediator interface. In this study, we compared the results from electrochemistry
      and photoelectron spectroscopy for determining the energy alignment of three
      rylene dyes, two of which absorb relatively far in the red. The trends observed
      with the methods were different, as in the former, the energy alignment is
      measured relative to an external reference and includes contributions from
      solvent reorganization energies, while in the latter, it is measured relative to
      the energetics of the TiO(2) and is lacking such contributions. The influence of
      the dyes' dipole moments on the energetics of the TiO(2) was also measured and
      explained some of the differences in trends. Finally, we compared the injection
      efficiencies of the two red-absorbing dyes and found that the differences in
      injection efficiencies can be better explained using the energy alignment
      determined from photoelectron spectroscopy. This shows that the method for
      measuring the energetics of a DSC should be chosen according to what process one
      intends to study.

PMID- 21743920
TI  - Sensitive fluorescence assay of anthrax protective antigen with two new DNA
      aptamers and their binding properties.
AB  - A homogeneous assay of the protective antigen in anthrax toxin is reported using
      two new PA-specific aptamers for selective and sensitive detection, based on
      reduction in the fluorescence emission according to the formation of the aptamer
      PA ternary complex. PA at 1 nM was readily detected using OliGreen as a
      fluorophore in HEPES buffer. We also demonstrated that the PA detection could be
      performed in blood serum. The binding interaction between the aptamer and PA was
      strong enough to dehybridize double-stranded DNA paired completely with 12 bases
      at room temperature. Moreover, this fluorescence study revealed that the binding
      sites of the two aptamers were located differently on the PA protein. We believe
      our approach may lay the groundwork for the real-time detection of PA.

PMID- 21743921
TI  - The electrostatic probe: a tool for the investigation of the Abeta(1-16) peptide
      deformations using the static modes.
AB  - We investigate the conformational changes of the Amyloid beta(1-16) peptide
      induced by moving Zn(2+) ions in the solvent, which we call the electrostatic
      probe. We use our recently developed approach of static modes which allows
      treating the flexibility of biological molecules at the atomic scale. Starting
      from an experimental apostructure, we find that several ion impacts allow the
      transition of the peptide toward its folded conformation, observed experimentally
      in the presence of Zn(2+) ions. This result shows the ability of our model and
      its associated software tool to describe properly the conformational changes and
      opens a new path toward the molecule/molecule docking problem.

PMID- 21743922
TI  - The electronic structure of Ullman's biradicals: an orthogonal valence bond
      interpretation.
AB  - This paper addresses the electronic structure of Ullman's organic biradical,
      bis(nitronyl) nitroxide, in the frame of ab initio wave function based methods,
      both using standard (delocalized) molecular orbital methods and a valence bond
      strategy based on orthogonal localized orbitals. The aim of this study is to
      clarify the origin of the magnetic coupling of this molecule and to understand
      the recently observed unexpected behavior of the computed magnetic coupling
      constant with respect to the use of different theoretical methods. A detailed
      analysis of the physical effects that govern the correct description of the main
      characteristics of the electronic structure, in particular the spin density,
      reveals that the wave functions of the radical fragments are better seen as
      arising from the interaction of three unpaired electrons and that the intuitive
      picture of one unpaired electron per fragment is oversimplified and can lead to
      incorrect results. Furthermore, we establish that both the triplet and the
      singlet wave functions are well represented by the antisymmetrized product of the
      two fragment wavefunctions, thus corroborating previous observations concerning
      the low weight of the ionic structures (hopping of one electron from one fragment
      to the other) in the biradical singlet wavefunction. The use of the orthogonal
      valence bond formalism has also allowed us to extract a set of parameters for the
      fragment (direct exchange, hopping integral, on-site repulsion) which can be used
      for larger magnetic systems in studies based on model Hamiltonians.

PMID- 21743923
TI  - Competitive wetting of acetonitrile and dichloromethane in comparison to that of
      water on functionalized carbon nanotube surfaces.
AB  - Differential wetting of pristine and ozonized carbon nanotubes has been studied
      using solvents like acetonitrile and dichloromethane in comparison to the well
      known wetting behavior of water. Based on their unique structural and physical
      properties, functionalized CNT substrates have been used due to the fact that
      independent variation in molecular as well as electronic properties could be
      controlled by understanding the wetting of these liquids on carbon nanotubes
      (CNTs), both pristine as well as ozone treated. The sensitivity of the wetting
      behavior with respect to molecular interactions has been investigated using
      contact angle measurements while Raman and XPS studies unravel the differential
      wetting behavior. Charge-transfer between adsorbed molecules and CNTs has been
      identified to play a crucial role in determining the interfacial energies of
      these two liquids, especially in the case of acetonitrile. Ozone treatment has
      been observed to affect the surface properties of pristine CNTs along with a
      concomitant change in the wetting dynamics.

PMID- 21743924
TI  - Coinage metal complexes of 2-diphenylphosphino-3-methylindole.
AB  - Coordination of P,N indolyl-phosphine ligands to Au(I), Ag(I) and Cu(I) metal
      ions under weakly basic conditions results in easy deprotonation of the indolyl N
      H function and effective formation of a family of homo- and heterobimetallic
      complexes MM'(PPh(2)C(9)H(7)N)(2) (M = M' = Au (2), Ag (5); M = Au, M' = Cu (3),
      Ag (4)). The latter (4) exists as an inseparable mixture of four different
      complexes, which are in equilibrium driven by slow dynamics. The reaction of
      silver(I) and copper(I) ions with PPh(2)(C(9)H(8)N) affords a rare tetranuclear Z
      shaped cluster Ag(2)Cu(2)(PPh(2)C(9)H(7)N)(4) (6), which exhibits red
      luminescence in solid state (650 nm) and a weak dual emission in solution with
      the main component in the near-IR region (746 nm).

PMID- 21743925
TI  - Chemistry of polynuclear transition-metal complexes in ionic liquids.
AB  - Transition-metal chemistry in ionic liquids (IL) has achieved intrinsic
      fascination in the last few years. The use of an IL as environmental friendly
      solvent, offers many advantages over traditional materials synthesis methods. The
      change from molecular to ionic reaction media leads to new types of materials
      being accessible. Room-temperature IL have been found to be excellent media for
      stabilising transition-metal clusters in solution and to crystallise homo- and
      heteronuclear transition-metal complexes and clusters. Furthermore, the use of IL
      as solvent provides the option to replace high-temperature routes, such as
      crystallisation from the melt or gas-phase deposition, by convenient room- or low
      temperature syntheses. Inorganic IL composed of alkali metal cations and
      polynuclear transition-metal cluster anions are also known. Each of these areas
      will be discussed briefly in this contribution.

PMID- 21743926
TI  - Alkane-oxidizing metalloenzymes in the carbon cycle.
AB  - This review examines the metalloenzymes that catalyze the oxidation of alkanes in
      the environment. The focus of the review is on what is known about the relative
      abundances of these metalloenzymes, their metal ion requirements, and their
      reaction mechanisms. The relative significance of these reactions in the global
      transformation of alkanes is discussed.

PMID- 21743927
TI  - Cellular uptake, evolution, and excretion of silica nanoparticles in human cells.
AB  - A systematic study on the interaction of silica nanoparticles (NPs) with human
      cells has been carried out in the present work. Endocytosis and exocytosis are
      identified as major pathways for NPs entering, and exiting the cells,
      respectively. Most of the NPs are found to be enclosed in membrane bounded
      organelles, which are fairly stable (against rupture) as very few NPs are
      released into the cytoplasm. The nanoparticle-cell interaction is a dynamic
      process, and the amount of NPs inside the cells is affected by both the amount
      and morphology (degree of aggregation) of NPs in the medium. These interaction
      characteristics determine the low cytotoxicity of SiO(2) NPs at low feeding
      concentration.

PMID- 21743928
TI  - Enantioselective fluorescent recognition of mandelic acid by unsymmetrical
      salalen and salan sensors.
AB  - As sensors with multiple chiral centers, salalen 1 and salan 2 composed of trans
      cyclohexane-1,2-diamine (trans-DACH) and 1,1'-bi-2-naphthol (BINOL) units were
      designed and synthesized. Fluorescent recognition studies of resulting sensors
      towards mandelic acid (MA) reveal that salan 2a containing (R)-BINOL and (R,R)
      DACH exhibits highly sensitive and enantioselective response towards MA. The
      relationship between the chirality combination and the enantioselectivity is
      discussed. Based on the studies of concentration and solvent effect on the
      recognition process of 2a, it was found that the sensitivity and
      enantioselectivity could be enhanced via changing the concentration of sensors or
      altering the polarity of solvents. To explain why higher enantioselectivity can
      be achieved in moderate polar solvent other than in nonpolar or polar solvent, a
      solvent-guest competition mechanism, which may shed a light on the enhancement of
      the enantioselectivity of chiral recognition and noncovalent asymmetric
      catalysis, has been proposed and validated.

PMID- 21743929
TI  - A redox-active [3]rotaxane capable of binding and electrochemically sensing
      chloride and sulfate anions.
AB  - A ferrocene functionalised redox-active [3]rotaxane which contains two
      interlocked anion recognition sites has been prepared by chloride anion
      templation. With chloride two equivalents of anion are bound, one in each of the
      interlocked cavities, while sulfate forms a 1:1 stoichimetric sandwich type
      complex; the rotaxane can also electrochemically sense the two anions in
      acetonitrile.

PMID- 21743930
TI  - Extraction of the surface trap level from photoluminescence: a case study of ZnO
      nanostructures.
AB  - Negative thermal quenching of both the excitonic and green emissions is observed
      in ZnO nanosheets, from which the energy level of surface traps can be extracted
      based on a model of multi-level transitions. The present study demonstrates a non
      destructive and easy method to determine the trap levels in semiconductor
      nanostructures.

PMID- 21743931
TI  - CH stretching vibration of N-methylformamide as a sensitive probe of its
      complexation: infrared matrix isolation and computational study.
AB  - The complexes between trans-N-methylformamide (t-NMF) and Ar, N(2), CO, H(2)O
      have been studied by infrared matrix isolation spectroscopy and/or ab initio
      calculations. The infrared spectra of NMF/Ne, NMF/Ar and NMF/N(2)(CO,H(2)O)/Ar
      matrices have been measured and the effect of the complexation on the
      perturbation of t-NMF frequencies was analyzed. The geometries of the complexes
      formed between t-NMF and Ar, N(2), CO and H(2)O were optimized in two steps at
      the MP2/6-311++G(2d,2p) level of theory. The four structures, found for every
      system at this level, were reoptimized on the CP-corrected potential energy
      surface; both normal and CP corrected harmonic frequencies and intensities were
      calculated. For every optimized structure the interaction energy was partitioned
      according to the SAPT scheme and the topological distribution of the charge
      density (AIM theory) was performed. The analysis of the experimental and
      theoretical results indicates that the t-NMF-N(2) and CO complexes present in the
      matrices are stabilized by very weak N-H...N and N-H...C hydrogen bonds in which
      the N-H group of t-NMF serves as a proton donor. In turn, the t-NMF-H(2)O complex
      present in the matrix is stabilized by O-H...O(C) hydrogen bonding in which the
      carbonyl group of t-NMF acts as a proton acceptor. Both, the theoretical and
      experimental results indicate that involvement of the NH group of t-NMF in
      formation of very weak hydrogen bonds with the N(2) or CO molecules leads to a
      clearly noticeable red shift of the CH stretching wavenumber whereas engagement
      of the CO group as a proton acceptor triggers a blue shift of this wavenumber.

PMID- 21743932
TI  - Reactions of simple and peptidic alpha-carboxylate radical anions with dioxygen
      in the gas phase.
AB  - alpha-Carboxylate radical anions are potential reactive intermediates in the free
      radical oxidation of biological molecules (e.g., fatty acids, peptides and
      proteins). We have synthesised well-defined alpha-carboxylate radical anions in
      the gas phase by UV laser photolysis of halogenated precursors in an ion-trap
      mass spectrometer. Reactions of isolated acetate (CH(2)CO(2)(-)) and 1
      carboxylatobutyl (CH(3)CH(2)CH(2)CHCO(2)(-)) radical anions with dioxygen yield
      carbonate (CO(3)(-)) radical anions and this chemistry is shown to be a hallmark
      of oxidation in simple and alkyl-substituted cross-conjugated species. Previous
      solution phase studies have shown that C(alpha)-radicals in peptides, formed from
      free radical damage, combine with dioxygen to form peroxyl radicals that
      subsequently decompose into imine and keto acid products. Here, we demonstrate
      that a novel alternative pathway exists for two alpha-carboxylate C(alpha)
      radical anions: the acetylglycinate radical anion (CH(3)C(O)NHCHCO(2)(-)) and the
      model peptide radical anion, YGGFG(-). Reaction of these radical anions with
      dioxygen results in concerted loss of carbon dioxide and hydroxyl radical. The
      reaction of the acetylglycinate radical anion with dioxygen reveals a two-stage
      process involving a slow, followed by a fast kinetic regime. Computational
      modelling suggests the reversible formation of the C(alpha) peroxyl radical
      facilitates proton transfer from the amide to the carboxylate group, a process
      reminiscent of, but distinctive from, classical proton-transfer catalysis.
      Interestingly, inclusion of this isomerization step in the RRKM/ME modelling of a
      G3SX level potential energy surface enables recapitulation of the experimentally
      observed two-stage kinetics.

PMID- 21743933
TI  - Electronic structure and lifetimes of GaX(2+) (X = N, O, F) in the gas phase.
      Unraveling stability trends.
AB  - High-level single-reference CCSD(T) and multireference MS-CASPT2/CASSCF ab initio
      calculations have been carried out to determine the electronic structure and the
      lifetimes of GaX(2+) (X = N, F) doubly charged diatomic systems. Lifetimes were
      evaluated using the Exterior Complex Scaling (ECS) method implemented with basis
      sets of B-spline functions. The results obtained led to the conclusion that both
      species GaN(2+) and GaF(2+) can be considered as bound systems in the gas phase.
      GaN(2+) is a kinetically stable dication, because although it is
      thermodynamically unstable with respect to its dissociation into Ga(+) ((1)S) +
      N(+) ((3)P) the barrier to be surmounted is rather high and wide, so that the
      lowest 14 vibrational states of this system are bound. GaF(2+) is found to be a
      thermodynamically stable species with respect to its dissociation into Ga(+)
      ((1)S) + F(+) ((1)D). With respect to its dissociation into Ga(+) ((1)S) + F(+)
      ((3)P), strictly speaking, it is metastable. However, the crossing between the
      attractive PEC and the repulsive one occurs at rather large internuclear
      distances, and therefore it can be only explored by highly vibrationally excited
      molecules. Thus, in practical terms GaF(2+) can be considered as a bound species.
      The behavior of GaN(2+) and GaF(2+) is in clear contrast with that predicted for
      GaO(2+), which was found to be metastable with respect to its dissociation into
      Ga(+) ((1)S) + O(+) ((4)S), with lifetimes in the range of ns to seconds. This
      seems to indicate that the primary factor governing the stability and lifetimes
      of these doubly charged diatomic species is the ionization energy of the atom X
      bound to Ga.

PMID- 21743934
TI  - Mono-carboxylated diaminedichloridoplatinum(IV) complexes--selective synthesis,
      characterization, and cytotoxicity.
AB  - (OC-6-43)-Dichlorido(N,N-dimethyl-ethane-1,2-diamine)dihydroxidoplatinum(IV)
      could selectively be mono-carboxylated with succinic anhydride based on the
      steric hindrance caused by the two methyl groups of the equatorial ligand.
      Subsequent esterification of the uncoordinated carboxylic acid with alcohols of
      different lengths (methanol, butanol, hexanol and octanol) afforded the
      corresponding esters. The synthesized complexes were characterized in detail by
      elemental analysis, ESI-MS, multinuclear ((1)H, (13)C, (15)N and (195)Pt) NMR
      spectroscopy and in two cases by X-ray crystallography. Cytotoxicity of novel
      platinum(IV) compounds was investigated in four human cancer cell lines (CH1,
      A549, SW480 and SK-OV-3). Remarkably, the most lipophilic complexes showed IC(50)
      values down to the low micromolar or even nanomolar range.

PMID- 21743935
TI  - Organomercury(II) and tellurium(II) compounds with the "pincer" ligand 2,6
      [O(CH2CH2)2NCH2]2C6H3--stabilization of an unusual organotellurium(II) cationic
      species.
AB  - The reaction of RH (1) with Hg(OAc)(2), in EtOH, gave the acetate RHgOAc (2) [R =
      2,6-[O(CH(2)CH(2))(2)NCH(2)](2)C(6)H(3)]. The corresponding RHgCl (3) was
      obtained from 2 and LiCl. The reaction of 3 with TeCl(4) (1:1 molar ratio), in
      anhydrous 1,4-dioxane, resulted in the transfer of the organic ligand from
      mercury to tellurium and the isolation of the unexpected ionic compounds
      [RTe](2)[Hg(2)Cl(6)] (4) and [RH(3)][HgCl(4)] (5). The molecular structures of 1
      4 and 5.H(2)O were established by single-crystal X-ray diffraction. The acetate 2
      and the chloride 3 are monomeric in solid state. In both mercury and tellurium
      organometallic compounds the organic group acts as an (N,C,N) "pincer" ligand.
      This coordination pattern provided stability for the rare [RTe](+) cation. Weak
      cation-anion interactions [Te...Cl 3.869(3) A] are present between [RTe](+) and
      the dinuclear anion [Hg(2)Cl(6)](2-) in the crystal of 4. Theoretical
      calculations with DFT methods were performed for models of 3 and 4. The results
      show that in the cation of 4 the coordination of the nitrogen atoms play an
      important role for the stabilization of the structure found in the crystal
      whereas in 3 the coordination of the nitrogen atoms to the metal centre
      stabilizes to a less extent the structure found in solid state.

PMID- 21743936
TI  - Origins of stereoselectivity in optically pure phenylethaniminopyridine tris
      chelates M(NN')3(n+) (M = Mn, Fe, Co, Ni and Zn).
AB  - One-pot reactions of 2-pyridinecarboxaldehyde, chiral phenylethanamines and
      Fe(II) give single diastereomer fac diimine complexes at thermodynamic
      equilibrium so that no chiral separations are required (d.r. > 200 : 1). The
      origins of this stereoselectivity are partly steric and partly a result of the
      presence of three sets of inter-ligand parallel-offset pi-stacking interactions.
      Mn(II), Co(II), Co(III), Ni(II) and Zn(II) give similar fac structures, alongside
      the imidazole analogues for Fe(II). While most of the complexes are paramagnetic,
      the series of molecular structures allows us to assess the influence of the pi
      stacking present, and there is a strong correlation between this and the M-N bond
      length. Fe(II) is close to optimal. For the larger Zn(II) ion, very weak pi
      stacking leads to poorer measured stereoselectivity (NMR) but this is improved
      with increased solvent polarity. The mechanism of stereoselection is further
      investigated via DFT calculations, chiroptical spectroscopy and the use of
      synthetic probes.

PMID- 21743937
TI  - Phenolate and phenoxyl radical complexes of Cu(II) and Co(III), bearing a new
      redox active N,O-phenol-pyrazole ligand.
AB  - The synthesis and characterisation of the new N,O-phenol-pyrazole pro-ligand,
      (pz)LH, comprising a pyrazole covalently linked to an o,p-di-tert-butyl
      substituted phenol, are herein reported. In CH(2)Cl(2) at room temperature, the
      cyclic voltammogram (CV) of (pz)LH exhibits a quasi-reversible one-electron
      oxidation process (at E(1/2) = 0.66 V vs. Fc(+)/Fc) attributed to the formation
      of the phenoxyl radical cation [(pz)LH](+). (pz)LH reacts with M(II)(BF(4))(2) (M
      = Cu, Co) in a 2:1 ratio to afford the bis-Cu(pz)L(2) (1) and tris-Co(pz)L(3) (2)
      complexes respectively. The X-ray structure of 1 reveals a Cu(II) ion in a square
      planar trans-Cu(II)-N(2)O(2) coordination environment whereas that of 2 consists
      of a Co(III) ion with an octahedral mer-N(3)O(3) coordination sphere; formed by
      the chelation of two (in 1) or three (in 2) N,O-bidentate phenolate ligands
      respectively. Both structures are preserved in CH(2)Cl(2) solution, as revealed
      by their NMR (for 2) and EPR (for 1) data. The CVs of 1 and 2 consist of two (at
      E(1/2): 0.43 and 0.58 V vs. Fc(+)/Fc) and three (E(1/2) = 0.12, 0.54 and 0.89 V
      vs. Fc(+)/Fc) reversible one-electron oxidation processes, respectively. The one
      electron electrochemical oxidation of 1 and 2 produces the oxidised species, 1(+)
      and 2(+), which are stable for several hours at room temperature under inert
      atmosphere in CH(2)Cl(2). The UV/vis and EPR data obtained for 1(+) and 2(+) are
      unambiguously consistent with the latter being formulated as Cu(II)- and Co(III)
      phenoxyl radical complexes, as [Cu(II)((pz)L)((pz)L)](+) and
      [Co(III)((pz)L)((pz)L)(2)](+) respectively.

PMID- 21743938
TI  - A microfluidic system to study cytoadhesion of Plasmodium falciparum infected
      erythrocytes to primary brain microvascularendothelial cells.
AB  - The cellular events leading to severe and complicated malaria in some Plasmodium
      falciparum infections are poorly understood. Additional tools are required to
      better understand the pathogenesis of this disease. In this technical report, we
      describe a microfluidic culture system and image processing algorithms that were
      developed to observe cytoadhesion interactions of P. falciparum parasitized
      erythrocytes rolling on primary brain microvascularendothelial cells. We isolated
      and cultured human primary microvascular brain endothelial cells in a closed loop
      microfluidic culture system where a peristaltic pump and media reservoirs were
      integrated onto a microscope stage insert. We developed image processing methods
      to enhance contrast of rolling parasitized erythrocytes on endothelial cells and
      to estimate the local wall shear stress. The velocity of parasitized erythrocytes
      rolling on primary brain microvascularendothelial cells was then measured under
      physiologically relevant wall shear stresses. Finally, we deployed this method
      successfully at a field site in Blantyre, Malawi. The method is a promising new
      tool for the investigation of the pathogenesis of severe malaria.

PMID- 21743939
TI  - Towards the computational modelling of polyoxoanions on metal surfaces: IR
      spectrum characterisation of [SiW12O40](4-) on Ag(111).
AB  - The adsorption of a polyoxometalate (POM) on a metal surface has been studied by
      means of a periodic plane wave DFT based method for the first time. In
      particular, we have analysed the most favourable adsorption sites of anion
      [SiW(12)O(40)](4-) on the Ag(111) surface and computed the infrared spectrum.
      Despite the intrinsic complexity of the system we have been able to fairly
      reproduce the observed IR spectrum and unambiguously discern the signal
      corresponding to W-O-Ag symmetric stretching, which appears at around 800 cm(-1).

PMID- 21743940
TI  - In situ solid-state NMR for heterogeneous catalysis: a joint experimental and
      theoretical approach.
AB  - In situ solid-state NMR is a well-established tool for investigations of the
      structures of the adsorbed reactants, intermediates and products on the surface
      of solid catalysts. The techniques allow identifications of both the active sites
      such as acidic sites and reaction processes after introduction of adsorbates and
      reactants inside an NMR rotor under magic angle spinning (MAS). The in situ solid
      state NMR studies of the reactions can be achieved in two ways, i.e. under batch
      like or continuous-flow conditions. The former technique is low cost and
      accessible to the commercial instrument while the latter one is close to the real
      catalytic reactions on the solids. This critical review describes the research
      progress on the in situ solid-state NMR techniques and the applications in
      heterogeneous catalysis under batch-like and continuous-flow conditions in recent
      years. Some typical probe molecules are summarized here to detect the Bronsted
      and Lewis acidic sites by MAS NMR. The catalytic reactions discussed in this
      review include methane aromatization, olefin selective oxidation and olefin
      metathesis on the metal oxide-containing zeolites. With combining the in situ MAS
      NMR spectroscopy and the density functional theoretical (DFT) calculations, the
      intermediates on the catalyst can be identified, and the reaction mechanism is
      revealed. Reaction kinetic analysis in the nanospace instead of in the bulk state
      can also be performed by employing laser-enhanced MAS NMR techniques in the in
      situ flow mode (163 references).

PMID- 21743941
TI  - Developmental outcomes and quality of life in children born preterm at preschool-
      and school-age.
AB  - OBJECTIVE: To review literature published in the last 5 years on the effects of
      premature birth on the development and quality of life of preschool- and school
      age children. SOURCES: Systematic review of empirical studies published in the
      last 5 years and indexed on PubMed, MEDLINE, LILACS, SciELO and PsycINFO.
      Keywords were chosen that relate prematurity to developmental and quality of life
      outcomes. SUMMARY OF THE FINDINGS: In the studies chosen, four global indicators
      of development were identified (neurological, neurodevelopment, executive
      functions and quality of life), in addition to seven specific indicators of
      development (cognition, motor function, behavior, language, academic performance,
      attention and memory). The most prevalent indicators were cognition and motor
      function. Premature children had worse performance in all developmental
      indicators than children born full term. Additionally, the younger the
      gestational age, the worse the performance in developmental indicator
      assessments. The studies identified both risk factors (lower birth weight,
      intraventricular hemorrhage and low maternal educational level) and protective
      factors (larger head circumference, breastfeeding and higher family income) for
      development of children born preterm. CONCLUSION: Children born extremely
      premature (<= 30 weeks' gestational age) are vulnerable to developmental and
      quality of life problems.

PMID- 21743942
TI  - [The role of recombinant activated factor VII in neuro- surgical and
      neurocritical patients].
AB  - Central nervous system haemorrhage is a severe pathology, as a small amount of
      bleeding inside the brain can result in devastating consequences. Haemostatic
      agents might decrease the consequences of intra- cranial bleeding, whichever
      spontaneous, traumatic, or anticoagulation treatment etiology. Proacogulant
      recombinant activated factor VII (rFVIIa) has been given after central nervous
      system bleeding, with an off-label indication. In this update, we go over the
      drug mechanism of action, its role in the treatment of central nervous system
      haemorrhage and the published evidences regarding this subject. We carried out a
      literature review concerning the treatment with rFVIIa in central nervous system
      haemorrhage, neurocritical pathologies and neurosurgical procedures, searching in
      MEDLINE and in clinical trials registry: http://clinicaltrials.gov (last review
      September 2010), as well as performing a manual analysis of collected articles,
      looking for aditional references. The results of randomized clinical trials do
      not support the systematic administration of rFVIIa for spontaneous intracranial
      cerebral haemorrhage. In other central nervous system related haemorrhages, the
      current available data consist on retrospective studies, expert opinion or
      isolated case reports.

PMID- 21743943
TI  - [Posterior spinal instrumentation image guided and assisted by neuronavigation.
      Experience in 120 cases].
AB  - INTRODUCTION: The authors present the results of a series of 121 cases of
      posterior vertebral fixation carried out from Sept 2008 to Sept 2010 using Flouro
      2D-TC assisted Vector Vision o Kolibri navigator. ( Brain LAB, Feldkirchen,
      Germany). MATERIAL: The sample included 68 males and 53 females. Age range was 24
      75 with an average of 50.35., all with indication for instrumentation by
      different pathologies. METHOD: Patients presenting vertebral lesions of varying
      ethiology and lesion level with vertebral posterior fixation indication were
      included in the study. All underwent a CT before surgery, according to navigation
      protocol, and the images obtained were merged in the navigator with those
      obtained in the operating room with a Flouro 2D, which allowed a high quality 3D
      reconstruction to be performed and thus the capacity to navigate in a real
      virtual manner. To evaluate the results of the implant a post-op CT was performed
      and the position of the implant was defined according to the Heary scale. The
      calabration time of the material was also evaluated, number of shots with the
      Flouro-2D, and for clinical evaluation VAS scales were employed, Oswestry and JOA
      (L), as well as the degree of satisfaction and acceptance of the procedure.
      RESULTS: A total of 580 screws were implanted, distributed in 62 cervicals of
      which 24 were in C1-C2, 38 dorsals, 370 lumbar and 110 sacral. Open surgery was
      performed in 42 cases, MIS in 28 and percutaneous in 51. The presision of the
      implant was 98.45% with a global deviation of 1.55%, that according to the Heary
      scale was distributed in grade ll: 2 (1 cervical, 1 lumbar) grade lll: 4 (1
      cervical, 2 dorsal, 1 lumbar), grade IV: 3 (1 cervical, 2 lumbar). General
      average time of calibration per procedure was 2 min. 49 seconds and the mean
      flouroscopic exposure was one shot at cervical and dorsal and two shots at lumbar
      level. The clinical evaluation at one month of 121 patients was 8.6/3.0 in the
      VAS, 68.0% / 23.0% in Oswestry and 6.4/13.1 in JOA (L), with those parameters
      remaining stable at 3 months in 100 and at 6 months in 87 patients respectively,
      and the degree of satisfaction between being completely and very satisfied with
      the procedure was 94.9%, and those who would submit to another treatment was more
      than 94%. CONCLUSION: Navigation with Flouro-2D-CT is a high precision technique
      that reduces complications of varying severity according to the level operated
      well as number of reinterventions, radiation exposure and surgical time.

PMID- 21743944
TI  - [Long-term outcomes of lumbar microdiscectomy in a working class sample].
AB  - INTRODUCTION: In the treatment of the lumbar disc herniaton (LDH) microdiscectomy
      constitutes one of the standard procedures. In the present study we have analyzed
      the clinical outcome of the lumbar microdis- cectomy in a series of worker
      patients who underwent surgery in our service. METHODS: Retrospective analysis
      and a 5-year follow up, of a series of 142 patients operated on by means of
      lumbar microdiscectomy in the 2004-2005 period. The clinical outcome was analyzed
      according to the "Herron and Turner" outline: pain reduction, use of medical
      treatment, restriction in the ability to perform physical activities, and return
      to work. RESULTS: 116 men and 26 women, with an average age of 37.9 and 45.4
      years respectively, underwent surgery because of LDH. In the clinical aspect,
      sciatica was predominant over low back pain in a ratio of three to one. The L5-S1
      discal level was operated on in 68.3% of the cases. It was considered that
      occupational activities gave rise to damage in 107 patients (75.3%). Besides a
      symptomatic disc, there was an additional injured disc in 44.3% of the cases. An
      initial unfavourable outcome was seen in 42 patients (33%), 15 of which recovered
      from in an interval of 3 months, and another fifteen within a one year period. A
      re-operation was necessa ry in 16 patients because of recurrent lumbar disc
      herniation (11%). Work reintegration was achieved in 83.3% (119/142) of the
      cases. After a 5-year follow up, we stated the consistency of the clinical
      result. DISCUSSION: We analyzed the intervertebral disc behaviour as regards sex,
      age, variety of discal herniation, additional disc, outcome and re-operation
      variables. After the analysis of the type of discal herniation and additional
      disc we defined three disc injury patterns. We consider microdiscectomy as the
      technique of choosing for the treatment of recurrence disc herniation.
      CONCLUSIONS: Between the working class, discal injury predominates in young men,
      as a consequence of the annulus breakage, or an annulus plus posterior
      longitudinal ligament breakage (traumatic herniae). Frequently it was observed
      that more than one disc was involved, and a left lateralization.

PMID- 21743945
TI  - [Combined anterior-posterior arthrodesis en patient with athetoid cerebral palsy
      who developed spondylotic cervical mielopathy. Case report and review of
      literature].
AB  - Spondylotic cervical mielopathy is a common complication in young patients with
      Cerebral Child Palsy with an important dystonic and athetoid component. Its
      surgical treatment is a challenge, due to elevate incidence of early faliure of
      the arthrodesis, both in anterior and posterior approaches. We report an
      historical review about the treatment of cervical mielopathy in this subgroup of
      patients and a clinical case in which we decided to realize decompression and
      arthtrodesis by a combined anterior and posterior approach, with lateral-mass
      screw placement, using botulinium toxin injections in the postoperative period,
      achieving a good clinical outcome.

PMID- 21743946
TI  - De novo basilar tip aneurysm. Case report and literature review.
AB  - The de novo aneurysms are the formation of new aneurysms in a location previously
      observed to be normal by a cerebral angiography or direct microsurgical
      exploration. In this report, we present a review of the theme and describe a case
      of a ruptured de novo basilar tip aneurysm in a patient previously treated with
      carotid occlusion for a giant intracavernous aneurysm and microsurgical clipping
      of contralateral posterior communicating artery aneurysm.

PMID- 21743947
TI  - [Isolated intracranial Rosai-Dorfman disease: a case report and literature
      review].
AB  - INTRODUCTION: Sinus histiocytosis with massive lymphadenopathy, also known as
      Rosai-Dorfman disease (RDD) is an idiopathic histiocytosis that usually affects
      the lymph nodes. Occasionally it may affect the CNS, being exceptional
      intracranial involvement without lymph node lesions. In the absence of typical
      radiological signs, affected patients are generally operated under the suspicion
      of a meningioma. The histological diagnosis is obtained after the surgical
      procedure. It is a clinicopathological entity not well known, controversy exists
      about its pathogenesis, clinical course and therapeutic management. CASE REPORT:
      We report the case of a 40-year-old male presented two generalized tonic-clonic
      seizures and brain MRI showed a left parieto-occipital extra-axial lesion
      extending into the posterior fossa, without presenting lesions at other levels. A
      partial resection of the lesion was performed and the histological findings were
      reported as Rosai-Dorfman disease. CONCLUSIONS: Despite its low frequency, the
      ERD should be included in the differential diagnosis of dural-based masses,
      compared to more common, such as meningiomas. Due to lack of specificity of
      additional studies its diagnosis is fundamentally histologic. More research is
      needed to define the best therapeutic option.

PMID- 21743948
TI  - [Chronic subgaleal hematoma in a child. Case report].
AB  - Neonatal subgaleal hematomas are under-diagnosed collections of blood beneath the
      galea, often caused by certain obstetric procedures such as use of forceps or
      vacuum. They generally have low volume and often resolve spontaneously.
      Occasionally, they can achieve a large volume and may endanger the live of the
      affected newborns. Rarely, they become chronic and exceptionally they may require
      surgical treatment. We report the case of a child under one year of age who was
      referred to our department because of a subgaleal hematoma secondary to vacuum
      assisted delivery that required surgical treatment.

PMID- 21743949
TI  - [Postoperative recurrence of subdural empyema].
AB  - We present a case of recurrent subdural post-surgical empyema by
      Proprionibacterium acnes after a first drained empyema in which no
      microbiological diagnosis was reached. P. acnes is a gram-positive anaerobic
      organism which is part of the saprophytic flora of the skin and others parts of
      the body. However, it can cause infections, as in the central nervous system,
      especially post-surgical infections in which can be the second more frequent
      organism after Staphylococcus aureus. P. acnes grows slowly and shows better
      growth in liquid anaerobic media. It is usually resistant to metronidazol and
      sensitive to penicillin. In postoperative central nervous system infections we
      must take into account the possibility of this organism, process the sample
      properly and keep touch with the Microbiology Department.

PMID- 21743950
TI  - [Postraumatic epidural arachnoid spinal cyst: case report].
AB  - INTRODUCTION: Extradural arachnoid spinal cysts are unfrequent lesions that are
      associated with spinal trauma, surgery and less frequently with congenital
      anomalies. The clinical manifestations are similar to those seen with other
      compressive spinal cord lesions. Magnetic resonance techniques allow to diagnose
      correctly this pathology and to define its thopographic situation. The pathologic
      history of the patient is essencial to establish the ethiology. Surgery is the
      elective treatment in most cases. CLINICAL CASE: The patient is a 35 years old
      man who has a medical history of penetrating spinal trauma two years ago. In that
      instance he suffered an unilateral spinal cord section at D2-D3 level with the
      corresponding Brown Sequard syndrome. A small wound was detected at the skin
      dorsal level and it was closed without difficulties. At the beginning, he
      improved his motor right leg function with rehabilitation and vitamins. After two
      years of good recovery he came to our hospital suffering a neurological
      deterioration of six months of evolution. The physical examination revealed an
      spastic paraparesis. Magnetic resonance was performed demonstrating a cystic
      extradural collection compressing the spinal cord at D3-D4 level. Surgical
      decompressive treatment allowed to excise the cyst and it was possible to define
      a dural tear that was closed successfully. The outcome was good with restoration
      of the initial motor function that he had after the spinal trauma. CONCLUSIONS:
      Surgical management of postraumatic epidural arachnoid spinal cyst allows to
      detect the meningeal tear and to close it, which is highly effective on these
      kinds of lesions.

PMID- 21743951
TI  - Perforating brain injury from a speargun. A case report.
AB  - A case of a perforating brain injury caused by a speargun in a suicide attempt is
      described. Although this kind of injuries has been previously reported, the
      present case is specially interesting because the patient showed no neurological
      deficit after surgery. Some advices about the medical and surgical management are
      proposed based on this case and our literature review. The use of antibiotics and
      antiepileptic drugs and the anterograde extraction of the harpoon aided by the
      performance of a craniotomy surrounding the exit point are recommended.

PMID- 21743952
TI  - Hard to reach: easy to omit.

PMID- 21743953
TI  - Correlation between peak flow and body mass index in  obese and non-obese
      children in Kocaeli, Turkey.
AB  - AIMS: To investigate the relationship between body mass index (BMI) and peak
      expiratory flow (PEF) values in children between the ages of 6 and 14 years.
      METHODS: Data were collected from 1,439 children during public health screening.
      Each child was classified on the basis of age- and sex-specific BMI percentile as
      non-obese or obese (BMI >95th percentile). PEF and BMI were compared among age
      sex-BMI percentile groups. RESULTS: PEF values were lower in obese children than
      in non-obese children. There were also significant differences between girls and
      boys. CONCLUSIONS: The association of higher BMI with lower PEF may indicate that
      obesity is an important risk factor for reduced airflow or lung function in
      children. These findings emphasise the importance of the prevention of obesity in
      children and adolescents in order to avoid possible future respiratory problems.

PMID- 21743954
TI  - Id1 induces tubulogenesis by regulating endothelial cell adhesion and
      cytoskeletal organization through beta1-integrin and Rho-kinase signalling.
AB  - The inhibitor of differentiation 1 (Id1) protein is required for tubulogenesis,
      but the molecular signalling pathways remain unclear. Overexpression (Id1-t) or
      down-regulation (si-Id1) of Id-1 in cell lines, were used to study the function
      of Id1. The expression of Id1 and beta1-integrin was assessed by Western
      blotting. Up-regulation of Id1 in human umbilical vascular endothelial cells
      (HUVECs) activated the expression of beta1-integrin and promoted cell adhesion
      and spreading. Conversely, down-regulation of Id1 suppressed beta1-integrin
      expression and inhibited tubulogenesis. By using a beta1-integrin antibody to
      inhibit beta1-integrin function, we demonstrated that Id1-induced cell adhesion
      and tubulogenesis were mediated by beta1-integrin. In addition, HUVECs
      overexpressing Id1 were able to promote capillary tube formation through
      cytoskeleton reorganization and cell contraction. Finally, the Rho-kinase
      inhibitor Y27632 inhibited tubulo-genesis induced by Id1. Our findings provide
      evidence that Id1 regulates tubulogenesis in vitro through beta1-integrin and Rho
      kinase signalling.

PMID- 21743955
TI  - Slit3 inhibits activator protein 1-mediated migration of malignant melanoma
      cells.
AB  - The repellent factor family of Slit molecules has been described to have
      repulsive function in the developing nervous system on growing axons expressing
      the Robo receptors. Alterations of the Slit/Robo system have been observed in
      various pathological conditions and in cancer. However, until today no detailed
      studies on Slit function on melanoma migration are available. Therefore, we
      analysed the mRNA expression in melanoma cells and found induction of Robo3
      expression compared to normal melanocytes. Functional assays performed with
      melanoma cells revealed that treatment with Slit3 led to strong inhibition of
      migration. Interestingly, we observed down-regulation of AP-1 activity and target
      gene expression after Slit3 treatment contributing to the negative regulation of
      migration. Taken together, our data showed that Slit3 reduces the migratory
      activity of melanoma cells, potentially by repulsion of the cells in analogy to
      the neuronal system. Further studies will be necessary to prove Slit activity in
      vivo, but due to its function, Slit3 activity may be helpful in the treatment of
      melanoma.

PMID- 21743956
TI  - Human papillomavirus infection and expression of ATPase family AAA domain
      containing 3A, a novel anti-autophagy factor, in uterine cervical cancer.
AB  - Our aim was to determine the association of human papillomavirus (HPV) infection
      with the expression of ATPase family AAA domain containing 3A (ATAD3A), an anti
      autophagy factor, in uterine cervical cancer (UCC). The HPV genotype was
      determined by an Easychip HPV blot assay. ATAD3A expression was determined by
      immunohistochemical staining. High-risk HPV (hrHPV) was detected in 184 (88.9%)
      of 207 UCC cases. ATAD3A expression was detected in 164 (79.2%) UCC cases. A
      significant correlation was found between ATAD3A expression and the presence of
      hrHPV (p<0.001), FIGO stage (p=0.014), lymph node involvement (p=0.001), c-MET
      expression (p<0.001), interleukin-8 (p=0.03) and patient survival (p=0.0016).
      Interestingly, silencing of E6/E7 expression decreased ATAD3A expression and cell
      survival. Moreover, knockdown of ATAD3A (ATAD3Akd) expression or addition of
      resveratrol, increased cellular autophagy and apoptosis and reduced drug
      resistance. Resveratrol reduced ATAD3A expression, and increased abrasion of the
      mitochondrial outer membrane as well as numbers of autophagosomes, the phenomena
      that were frequently found in ATAD3Akd cells. In conclusion, our results show
      that HPV infection correlates with increased ATAD3A expression and drug
      resistance in UCC. Persistent HPV infection may stabilize ATAD3A expression to
      inhibit cell autophagy and apoptosis as well as to increase drug resistance.

PMID- 21743957
TI  - Oxygen- and glucose-deprived culture promotes cell proliferation and invasion of
      vascular smooth muscle cells.
AB  - Excessive proliferation of vascular smooth muscle cells (VSMCs) is an important
      reason for the formation and development of many vascular remodeling diseases. In
      pathological conditions, necrosis of VSMCs may result in the release of
      inflammatory cytokines, which can lead to stimulation of other normal smooth
      muscle cells, and promote the proliferation of VSMCs. The purpose of this study
      was to investigate the effect of oxygen- and glucose-deprived (OGD) conditioned
      medium on VSMC cell proliferation and invasion. Following culture of VSMCs in OGD
      conditioned medium, the cell cycle distributions were remarkably altered. The
      number of cells in the G0/G1 phase decreased, while the number of cells in G2/M
      and S phase increased. The expression of cell cycle proteins D1 (Cyclin D1) in
      VSMCs increased correspondingly. These results suggested that after being
      cultured in OGD medium, VSMCs can pass through the G0/G1 phase by up-regulation
      of Cyclin D1 expression, and promote cell proliferation. In addition, we found
      that the expression of matrix metalloproteinase (MMP)-2 and MMP-9 was increased
      in OGD medium cultured VSMCs. Using a Transwell invasion assay, we showed that
      the OGD medium enhanced VSMC cell invasion. These results suggest that MMP-2 and
      MMP-9 degraded the basement membrane and promoted VSMC invasion. Taken together,
      our data demonstrate that OGD-conditioned medium can promote VSMC proliferation
      and invasion by up-regulating Cyclin D1 and MMP-2 and MMP-9 expression, which may
      contribute to the formation and development of vascular remodeling diseases.

PMID- 21743958
TI  - Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with
      decreased expression of AP-1 and NF-kappaB.
AB  - Previous studies suggest that the effects of Egr-1 on tumorigenesis are
      critically dependent on the levels of Egr-1 and the cellular context. For this
      reason, we examined the effects of blocking the Egr-1 activity by a short
      interfering RNA (siRNA) against Egr-1 on the expression of nuclear factor-kappaB
      (NF-kappaB) and activator protein-1 (AP-1) signaling in the PC-3 and LNCaP
      prostate carcinoma cell lines. We observed that the reduction in expression of
      Egr-1 in PC-3 and LNCaP cells by effects of the siRNA vector resulted in lower
      cell viability and increased apoptosis at 24 and 120 h after transfection. This
      reduced cell viability correlated well with a reduced activity of the NF-kappaB
      and AP-1 factors. We analyzed the expression and activity of these factors and
      found that p65 and IkappaB but not p50 were reduced in the siRNA-treated cells.
      Similarly, we found that c-Fos but not c-Jun was reduced in the siRNA treated
      cells. These effects were translated to reduced transcriptional activity of NF
      kappaB over cellular inhibitor of apoptosis (cIAP) and p21 genes, as assayed by
      RT-PCR and of AP-1 over a luciferase reporter activated by AP-1 response
      elements. Egr-1 was also found to interact directly with p65 and IkappaB members
      of the NF-kappaB family, thereby was able to regulate directly their activity by
      post-transcriptional effects. These results suggest that Egr-1 may promote
      prostate cancer development by modulating the activity of factors NF-kappaB and
      AP-1, which are involved in cell proliferation and apoptosis.

PMID- 21743959
TI  - Analysis of laser-microdissected prostate cancer tissues reveals potential tumor
      markers.
AB  - Prostate cancer (PCA) is a clinically heterogeneous and often multifocal disease
      with a clinical outcome difficult to predict. A deeper knowledge of the molecular
      basis of the disease may lead to a better prediction of prognosis. Therefore, in
      this study we investigated the molecular basis of PCA by identifying potential
      tumor markers in laser-microdisected PCA tissues. Among a group of PCA patients,
      quantitative RT-PCR analysis was performed to compare the expression of 70 genes.
      These genes were selected from the results of two microarrays which investigated
      the gene expression profile differences between moderately or poorly
      differentiated prostate carcinoma glands and the corresponding normal glands.
      Among the genes examined, CDKN2A, GATA3, CREBBP, ITGA2, NBL1 and TGM4 were down
      regulated in the prostate carcinoma glands compared to the corresponding normal
      glands, whereas TFF3, TMPRSS2 and ERG were up-regulated. Our findings indicate
      that these genes may play roles as tumor suppressor genes or oncogenes in PCA,
      and may serve as potential tumor markers and novel therapeutic targets.

PMID- 21743960
TI  - Prognostic impact of disseminated tumor cells and microRNA-17-92 cluster
      deregulation in gastrointestinal cancer.
AB  - The presence of tumor cells in the bone marrow (BM) could be relevant to
      identifying high risk of disease progression and death in gastrointestinal
      cancer. However, the molecular profile associated with disseminated tumor cells
      (DTCs) homing to the BM has yet to be defined. MicroRNAs (miRNA) play key roles
      in cellular processes implicated in cancer. Thus, we investigated in 38 patients
      with colorectal, gastric or pancreatic cancer whether the presence of BM-DTCs is
      associated with a specific miRNA tumor profile and analyzed their potential
      prognostic impact. DTCs were detected by immunocytochemistry and anti-cytokeratin
      antibodies in 42.1% of the patients. miRNAs were isolated from formalin-fixed,
      paraffin-embedded tumors. qRT-PCR was used for miRNA profiling. No significant
      associations were found among DTC detection and miRNA deregulation. Kaplan-Meier
      curves demonstrated significantly reduced progression-free survival (PFS) and
      overall survival (OS) in the DTC-positive patients. Although miR-21 was
      upregulated in 90.6% of the tumors, no associations with outcomes were found. miR
      17 and miR-20a (miRNA-17-92 cluster) were upregulated in 33.3 and 42.4%,
      respectively. Upregulation of both was correlated and found in 30.3%. Univariate
      analysis shows that increasing values for miR-20a were significantly associated
      with reduced PFS (HR 1.022; p=0.016) and OS (HR 1.027; p=0.003). In multivariate
      Cox models, DTC positivity (HR 4.07; p=0.005) and miR-17 overexpression (HR 2.11;
      p=0.003) were significantly associated with a higher risk of disease progression.
      The presence of DTCs in the BM (HR 3.98; p=0.010) and a miR-17 overexpression (HR
      2.62; p<0.001) were also associated with a risk of death. Our study suggests that
      the presence of BM-DTCs and the upregulation of the miR-17-92 cluster in tumors
      are both significant but independent prognostic markers in gastrointestinal
      cancer patients.

PMID- 21743961
TI  - Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells:
      Identification of novel targets.
AB  - Epidemiological and clinical observations provide consistent evidence that
      regular intake of aspirin may effectively inhibit the occurrence of epithelial
      tumors; however, the molecular mechanisms are not completely understood. In the
      present study, we determined the ability of aspirin to acetylate and post
      translationally modify cellular proteins in HCT-116 human colon cancer cells to
      understand the potential mechanisms by which it may exerts anti-cancer effects.
      Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the
      acetylation of multiple proteins whose molecular weight ranged from 20 to 200
      kDa. The identity of these proteins was determined, using immuno-affinity
      purification, mass spectrometry and immuno-blotting. A total of 33 cellular
      proteins were potential targets of aspirin-mediated acetylation, while 16 were
      identified as common to both the control and aspirin-treated samples. These
      include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal
      and mitochondrial proteins. The glycolytic enzymes which were identified include
      aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2,
      and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that
      aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both
      enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In
      vitro assays of these enzymes revealed that aspirin did not affect pyruvate
      kinase and lactate dehydrogenase activity; however, it decreased glucose 6
      phosphate dehydrogenase activity. Similar results were also observed in HT-29
      human colon cancer cells. Selective inhibition of glucose-6-phosphate
      dehydrogenase may represent an important mechanism by which aspirin may exert its
      anti-cancer effects through inhibition of ribonucleotide synthesis.

PMID- 21743962
TI  - Fragmented hyaluronan is an autocrine chemokinetic motility factor supported by
      the HAS2-HYAL2/CD44 system on the plasma membrane.
AB  - Hyaluronan (HA) is synthesized by HA synthase (HAS) 1, HAS2 and HAS3, and
      degraded by hyaluronidase (HYAL) 1 and HYAL2 in a CD44-dependent manner. HA and
      HYALs are intricately involved in tumor growth and metastasis. Random cell
      movement is generally described as chemokinesis, and represents an important step
      at the beginning of tumor cell liberation from the primary site. To investigate
      the roles of HAS2 and HYAL2/CD44 in cell motility, we examined HeLa-S3 cells
      showing spontaneous chemokinesis. HeLa-S3 cells expressed HAS2 and HAS3. siRNA
      mediated knockdown of HAS2 decreased spontaneous chemokinesis of HeLa-S3 cells.
      Although HeLa-S3 cells secreted 50 ng/ml of high molecular weight (HMW)-HA (peak:
      990 kDa) into the culture supernatant after 6 h of culture, exogenously added HMW
      HA did not enhance spontaneous chemokinesis of the cells. These observations
      suggested that HeLa-S3 cells may have a self-degrading system for HA to regulate
      their spontaneous chemokinesis. To examine this possibility, we investigated the
      effects of siRNA-mediated knockdown of HYAL2 or CD44 on the spontaneous
      chemokinesis of HeLa-S3 cells. Knockdown of either molecule decreased the
      spontaneous chemokinesis of the cells. Low molecular weight (LMW)-HA (23 kDa)
      reversed the HYAL2 siRNA-mediated reduction in spontaneous chemokinesis of HeLa
      S3 cells to the level in control cells stimulated with the same HA. These
      findings indicate that the HAS2-HYAL2/CD44 system may support spontaneous
      chemokinesis of human cancer cells through self-degradation of HMW-HA to produce
      LMW-HA by an autocrine mechanism. Consequently, our study may further expand our
      understanding of HA functions in cancer.

PMID- 21743963
TI  - Enhanced antitumor efficacy by the combination of emodin and gemcitabine against
      human pancreatic cancer cells via downregulation of the expression of XIAP in
      vitro and in vivo.
AB  - XIAP and NF-kappaB play an important role in chemotherapy resistance in
      pancreatic cancer. The purpose of this study was to explore the role of XIAP and
      NF-kappaB in potentiating the antitumor effect of gemcitabine by emodin in
      pancreatic cancer. SW1990 cells were treated by sodium chloride, gemcitabine,
      emodin or their combination (gemcitabine plus emodin). Cellular proliferation and
      apoptosis were detected by Cell Counting kit-8 (CCK-8) assay and flow cytometry
      in vitro. The combination therapy more significantly inhibited SW1990 cell growth
      and induced a higher percentage of apoptosis than monotherapy. Gemcitabine
      upregulated the expression of XIAP and NF-kappaB, while emodin or emodin plus
      gemcitabine downregulated them compared to the control group in vitro. SW1990
      cells were used to establish orthotopic pancreatic tumor models in nude mice.
      Tumor-bearing mice were treated with sodium chloride, emodin, gemcitabine or
      their combination. After being treated for 4 weeks, the nude mice were imaged
      with high-resolution positron emission tomography (microPET) and fluorine-18
      labeled fluorodeoxyglucose (18F-FDG) to detect the tumor/non-tumor ratio (T/NT
      ratio) and standard uptake value (SUV). The mice were sacrificed to determine
      tumor weight. The combination of emodin and gemcitabine showed more significant
      reduction in the T/NT ratio, SUV and tumor weight compared to monotherapy. The
      mRNA levels and the protein expression of XIAP and NF-kappaB were upregulated in
      the gemcitabine group, while they were downregulated in the emodin group and the
      combination group in vivo. Ki-67 prolif-eration index and TUNEL assay results
      also showed that emodin enhanced tumor apoptosis induced by gemcitabine in vivo.
      This study suggests that emodin enhances the antitumor effect of gemcitabine in
      SW1990 pancreatic cancer in vitro and in vivo, which may be via the
      downregulation of NF-kappaB expression, thus inhibiting the expression of XIAP.

PMID- 21743964
TI  - The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL
      in prostate cancer cells.
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous
      agent that induces apoptosis selectively in cancer cells. Soluble or expressed in
      immune cells, TRAIL plays an important role in the defense against tumour cells.
      The resistance of cancer cells to TRAIL immune surveillance is implicated in
      tumour development. Naturally occurring flavonoids can sensitize TRAIL-resistant
      cancer cells and augment their apoptotic activity. Fisetin, a dietary flavonol
      has cancer preventive properties. This study was designed to investigate the
      effect of fisetin on the TRAIL-induced apoptosis potential in prostate cancer
      cells. Prostate cancer cell lines represent an ideal model for research in
      chemoprevention. Cytotoxicity was measured by MTT and LDH assays. Apoptosis was
      detected using Alphannexin V-FITC by flow cytometry and fluorescence microscopy.
      Mito-chondrial membrane potential (DeltaPsim) was evaluated using DePsipher
      staining by fluorescence microscopy. Death receptor (TRAIL-R1 and TRAIL-R2)
      expression was analysed by flow cytometry. Inhibition of NF-kappaB (p65)
      activation was confirmed with an ELISA-based TransAM NF-kappaB kit. Caspase-8 and
      caspase-3 activities were determined by colorimetric protease assays. Our study
      demonstrates that fisetin sensitizes the TRAIL-resistant androgen-dependent LNCaP
      and the androgen-independent DU145 and PC3 prostate cancer cells to TRAIL-induced
      death. Fisetin augmented TRAIL-mediated cytotoxicity and apoptosis in prostate
      cancer LNCaP cells by engaging the extrinsic (receptor-mediated) and intrinsic
      (mitochondrial) apoptotic pathways. Fisetin increased the expression of TRAIL-R1
      and decreased the activity of NF-kappaB. Co-treatment of cancer cells with TRAIL
      and fisetin caused significant activation of caspase-8 and caspase-3 and
      disruption of DeltaPsim. Our data indicate the usefulness of fisetin in prostate
      cancer chemoprevention through enhancement of TRAIL-mediated apoptosis.

PMID- 21743965
TI  - Protein profiling of angiogenesis-related growth factors in laryngeal carcinoma:
      Pattern of protein expression in relation to tumour progression.
AB  - The expression of angiogenesis-related proteins was determined in laryngeal
      tumour tissue, associated tumour involved lymph nodes, apparently normal mucosa
      and control tissue and were related to tumour stage. Both laryngeal tumour tissue
      and associated metastatic nodes were obtained from seven patients undergoing
      surgical resection; in four cases apparently normal mucosa was also dissected
      from the tumour specimen margins. Control uvula mucosa was obtained from five
      healthy volunteers undergoing uvulopalatopharyngoplasty. The relative expression
      of 55 angiogenesis-related proteins was determined in tissue lysates using a
      Proteome Profiler human angiogenesis array kit. The level of 32/55 angiogenesis
      related proteins was higher in tumour tissue compared with controls. Furthermore,
      in these tumour biopsies higher levels of proteins were associated with
      increasing tumour stage. A similar trend was seen for 29/32 of these proteins in
      the nodal tissue. In T4 stage tumour tissue samples, 29/55 angiogenensis-related
      proteins were more highly expressed compared with the adjacent normal mucosa from
      the same patient, and this decreased to 8 proteins in tumour tissue from the T1
      stage patients. In contrast, the expression of 23 angiogenesis-related proteins
      in metastatic lymph node tissue from T4 stage patients was lower compared with
      that found in the normal mucosa adjacent to the tumour. In conclusion, this study
      has identified a number of factors involved in angiogenesis that are likely to
      contribute to the growth and metastasis of laryngeal tumours. Furthermore, a
      number of factors were also substantially altered in metastatic deposits compared
      with the primary tumour mass or adjacent normal tissue. This study requires
      confirmatory analysis of the selected key factors in a larger cohort of patients.

PMID- 21743966
TI  - Proteomic approaches to study epigallocatechin gallate-provoked apoptosis of TSGH
      8301 human urinary bladder carcinoma cells: roles of AKT and heat shock protein
      27-modulated intrinsic apoptotic pathways.
AB  - Epigallocatechin-3-gallate (EGCG), a polyphenol constituent present in green tea,
      has been shown to inhibit the growth of cancer cells in vitro and in vivo.
      However, studies regarding human bladder carcinoma cells are limited and not well
      investigated. Hence, our study focused on the evaluation of EGCG-triggered
      apoptosis in TSGH-8301 human urinary bladder carcinoma cells in vivo and in vitro
      as well as its related molecular mechanisms. In an in vivo study, EGCG inhibited
      xenograft tumor size of TSGH-8301 cells in a nude mouse model. Based on an in
      vitro study, EGCG resulted in morphological changes and increased growth
      inhibition in a dose- and time-dependent manner in TSGH-8301 cells. Furthermore,
      sub-G1 populations were shown and caspase-9 and -3 activities were stimulated in
      EGCG-treated TSGH-8301 cells. Moreover, a caspase-9 inhibitor (Z-LEHD-FMK) and a
      caspase-3 inhibitor (Z-DEVD-FMK) were able to reduce EGCG-stimulated caspase-9
      and -3 activities, respectively. Loss of mitochondrial membrane potential (?Psim)
      resulted in an increase of protein levels of cytochrome c, Apaf-1, caspase-9 and 
      3 in TSGH-8301 cells following exposure to EGCG. Proteomic analysis revealed that
      EGCG affected the expression levels of various proteins, including HSP27, porin,
      tropomyosin 3 isoform 2, prohibitin and keratin 5, 14, 17 in TSGH-8301 cells.
      EGCG also suppressed AKT kinase activity and protein levels and also altered the
      expression levels of Bcl-2 family-related proteins such as Bcl-2, Bax, BAD and p
      BAD. Based on the above findings, this study suggests that EGCG-provoked
      apoptotic death in TSGH-8301 cells is mediated through targeting AKT and HSP27
      and modulating p-BAD, leading to activation of the intrinsic apoptotic pathway.

PMID- 21743967
TI  - Overexpression of Nampt in gastric cancer and chemopotentiating effects of the
      Nampt inhibitor FK866 in combination with fluorouracil.
AB  - Nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the NAD+
      salvage pathway, is over-expressed and important in the carcinogenesis in several
      types of cancers. The expression of Nampt and its role in gastric cancer remain
      largely unknown. In this study, using real-time PCR and Western blotting we found
      that Nampt was overexpressed at the mRNA and protein levels, respectively, in
      established gastric cancer cells and human gastric cancer tissues. The specific
      Nampt inhibitor FK866 repressed gastric cancer cell proliferation, as assessed by
      MTT assay. Using transwell and soft agar clonogenic assays, we also found that
      FK866 suppressed gastric cancer cell migration and anchorage-independent growth,
      respectively. These inhibitory effects of FK866 were accompanied by significantly
      decreased expression of VEGF, MMP2, MMP9 and NF-kappaB. As determined by MTT
      assay and flow cytometry, FK866 also increased the chemo-sensitivity of gastric
      cancer cells to fluorouracil by greater inhibition of cell proliferation and the
      induction of apoptosis. Our findings indicate that Nampt may be a new therapeutic
      target for gastric cancer.

PMID- 21743968
TI  - Inhibin-alpha subunit in normal and malignant human cervical tissue and cervical
      cancer cell lines.
AB  - Inhibins are dimeric glycoproteins composed of an alpha-subunit and one of two
      possible beta-subunits (betaA or betaB), with substantial roles in human
      reproduction and in endocrine-responsive tumours. Four normal cervical tissue
      samples together with 10 specimens of well-differentiated squamous cervical
      cancer and adenocarcinoma of the cervix were immunohistochemically analysed for
      the expression of the inhibin-alpha subunit. Additionally, two cervical carcinoma
      cell lines (HeLa and CaSKi) were analysed with immunofluorescence and RT-PCR for
      the expression of the inhibin-alpha subunit. We demonstrated for the first time
      an immunolabelling of the inhibin-alpha subunit in normal and malignant cervical
      tissue, as well as cervical cancer cells. However, the immunoreactive reaction
      was albeit weak and mostly confined to mitotic cells in the analysed cervical
      tissues. Additionally, the expression pattern of this subunit was rather
      inconsistent. Therefore, the immunohistochemical evaluation of this subunit in
      cervical tissue cannot be used as a prognostic marker as suggested for
      endometrial cancer. However, since the expression of the inhibin-alpha subunit is
      minimal in HeLa cells as assessed by immunofluorescence and RT-PCR, the CaSKi
      cell line might be a better model for further functional experiments regarding
      cervical pathogenesis.

PMID- 21743969
TI  - Notch-1 activation-dependent p53 restoration contributes to resveratrol-induced
      apoptosis in glioblastoma cells.
AB  - Glioblastoma is the most malignant form of adult brain tumor and is associated
      with a dismal prognosis. Emerging data suggest that Notch signaling participates
      principally in the formation and malignant progression of glioblastoma.
      Resveratrol is a terpenoid that exhibits broad pro-apoptotic activity in various
      types of cancers, including glioblastoma. However, the effects of resveratrol on
      Notch signaling in glioblastomas have not yet been fully elucidated. We
      demonstrated that resveratrol strongly suppressed cell growth and induced
      apoptosis in A172 and T98G glioblastoma cells, which have low active Notch-1
      expression and a heterozygous p53 mutation. Our results suggest that resveratrol
      significantly activates intracellular Notch-1 and restores wild-type p53
      expression in a time-dependent manner. Significant de-phosphorylation of Akt,
      increased Bax expression, decreased Bcl-2 expression and cleavage of caspase-3
      were also observed in resveratrol-induced apoptosis in glioblastoma cells.
      Moreover, simultaneous treatment with resveratrol and a Notch-1 inhibitor (MRK
      003) partially attenuated the apoptosis and completely blocked the activation of
      Notch-1 and the increase in wild-type p53. This suggests that restoration of wild
      type p53 expression depends on Notch-1 activation. In addition, the de
      phosphorylation of Akt, increased expression of Bax and cleavage of caspase-3
      were not fully reversed by MRK-003 treatment, suggesting that p53 restoration is
      not the only mechanism underlying resveratrol-induced apoptosis. Taken together,
      we confirmed the anti-proliferative and pro-apoptotic effects of resveratrol on
      glioblastoma cells and revealed Notch-1 activation-dependent restoration of p53
      as an important causative mechanism.

PMID- 21743970
TI  - Chemotherapy-induced modification of microRNA expression in esophageal cancer.
AB  - Neoadjuvant chemotherapy is often used in the treatment of advanced esophageal
      cancer. In this study, we determined the impact of chemotherapy on microRNA
      (miRNA) expression in esophageal cancer cells, and whether identified changes
      might have biological relevance. Two esophageal carcinoma cell lines (one
      adenocarcinoma and one squamous cell carcinoma) were treated with cisplatin or 5
      fluorouracil for 24 or 72 h. RNA was extracted from cells following 24-h
      treatment, and used for microarray studies. Promising miRNA candidates were
      selected for RT-PCR validation. Target prediction using TargetScan, combined with
      bioinformatic analysis (Ingenuity Pathway Analysis, IPA), was performed to
      evaluate the implications of the altered miRNA expression. Thirteen miRNAs (miR
      199a-5p, miR-302f, miR-320a, miR-342-3p, miR-425, miR-455-3p, miR-486-3p, miR
      519c-5p, miR-548d-5p, miR-617, miR-758, miR-766, miR-1286) were deregulated after
      24- and/or 72-h treatment in both cell lines, and most miRNAs presented similar
      expression changes after short- or long-term exposure. IPA revealed that the
      major networks which incorporate the predicted targets, include functions such as
      'Cell death', 'Cell cycle', 'Cellular growth and proliferation', 'DNA
      replication, recombination, and repair' and 'Drug metabolism'. Cisplatin or 5
      fluorouracil alter miRNA expression in esophageal cancer cells. IPA suggests that
      these miRNAs may target molecular pathways involved in cell survival after
      chemotherapy.

PMID- 21743971
TI  - In vitro and in vivo antitumor effects of recombinant bispecific antibodies based
      on humanized anti-EGFR antibody.
AB  - We performed in vitro and in vivo experiments of the anti-epidermal growth factor
      receptor (EGFR) x anti-CD3 bispecific diabody (hEx3-Db) with the IgG-like
      bispecific antibodies (BsAbs) (hEx3-scFv-Fc and hEx3-scDb-Fc) and the anti-EGFR
      therapeutic antibody cetuximab to assess the effect of BsAbs on cancer growth
      inhibition. In vitro, efficacy of the BsAbs and cetuximab were compared by growth
      inhibition assays of human cell lines of bile duct (TFK-1, HuCC-T1, OCUCh-LM1),
      epidermoid (A431), gastric (Kato-III), colon (DLD-1, SW480), and breast (SK-BR-3,
      MCF-7) cancer. In vivo, in three mouse models, we evaluated the anti-tumor
      activity of hEx3-Db and cetuximab, assessed the effect of hEx3-Db alone, and
      compared the antitumor activity of hEx3-Db with the IgG-like BsAbs. In vitro,
      hEx3-scFv-Fc showed nearly 100% killing activity for all cell lines. Both in
      vitro and in vivo, hEx3-Db needed CD3-positive phenotypes to induce a growth
      inhibitory effect. In contrast, IgG-like BsAbs showed monotherapeutic effects in
      vivo by inducing antibody-dependent cellular cytotoxicity (ADCC) similar to
      cetuximab. However, enhancement was not observed when lymphokine-activated killer
      cells with the T-cell phenotype were co-injected. Results suggest that IgG-like
      BsAbs could not efficiently direct T lymphocytes toward tumor cells to induce
      ADCC due to steric hindrance on binding to CD3- and Fc-receptor-positive
      phenotypes. Although hEx3-scFv-Fc showed high cytotoxicity in vitro, its high
      molecular weight limits its usefulness. With an in vivo effect comparable to hEx3
      scFv-Fc and its realistic molecular weight, hEx3-scDb-Fc shows promise as a novel
      recombinant therapeutic antibody and may be modified to enhance its potency by
      prevention of steric hindrance.

PMID- 21743972
TI  - Silencing of the human TERT gene by RNAi inhibits A549 lung adenocarcinoma cell
      growth in vitro and in vivo.
AB  - Human telomerase reverse transcriptase (hTERT) is the catalytic subunit and the
      activity determinant factor of the telomerase enzyme which maintains the length
      of human chromosomes. In recent years it has become an attractive molecular
      target for cancer gene therapy. In the present study, we show that hTERT siRNA
      effectively suppressed the expression of hTERT mRNA and hTERT protein levels,
      reduced telomerase activity, and induced apoptosis of A549 lung adenocarcinoma
      cells (P<0.05). In vivo, tumors treated with the hTERT siRNA were of reduced
      sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of
      lung adenocarcinoma cells (P<0.05). These results demonstrate that hTERT siRNA
      can cause effective suppression of telomerase and lead to apoptosis in A549 lung
      adenocarcinoma cells. hTERT siRNA may, therefore, be a strong candidate for
      highly selective therapy for chemoprevention and treatment of lung
      adenocarcinoma.

PMID- 21743974
TI  - Successful pregnancy after recryopreservation by vitrification of one blastocyst
      developed from a frozen embryo obtained by PESA: case report.

PMID- 21743973
TI  - Preimplantation genetic screening: does it help or hinder IVF treatment and what
      is the role of the embryo?
AB  - Despite an ongoing debate over its efficacy, preimplantation genetic screening
      (PGS) is increasingly being used to detect numerical chromosomal abnormalities in
      embryos to improve implantation rates after IVF. The main indications for the use
      of PGS in IVF treatments include advanced maternal age, repeated implantation
      failure, and recurrent pregnancy loss. The success of PGS is highly dependent on
      technical competence, embryo culture quality, and the presence of mosaicism in
      preimplantation embryos. Today, cleavage stage biopsy is the most commonly used
      method for screening preimplantation embryos for aneuploidy. However, blastocyst
      biopsy is rapidly becoming the more preferred method due to a decreased
      likelihood of mosaicism and an increase in the amount of DNA available for
      testing. Instead of using 9 to 12 chromosome FISH, a 24 chromosome detection by
      aCGH or SNP microarray will be used. Thus, it is advised that before attempting
      to perform PGS and expecting any benefit, extended embryo culture towards day 5/6
      should be established and proven and the clinical staff should demonstrate
      competence with routine competency assessments. A properly designed randomized
      control trial is needed to test the potential benefits of these new developments.

PMID- 21743977
TI  - Colorectal liver metastasis in the setting of lymph node metastasis: defining the
      benefit of surgical resection.
AB  - BACKGROUND: For patients with colorectal liver metastasis (CLM), the presence of
      concomitant perihepatic/para-aortic lymph node metastasis (LNM) is considered a
      contraindication to liver resection. We sought to determine the benefits of liver
      resection among patients with CLM + LNM by examining long-term outcomes among a
      large cohort of patients. METHODS: Between October 1996 and December 2007, 61
      patients with CLM and pathologically proven LNM were identified from an
      international multi-institutional database of 1629 patients. The effect of LNM,
      as well as other prognostic factors, on recurrence-free and overall survival was
      analyzed. RESULTS: Median overall survival was 32 months, and 1-, 3-, and 5-year
      overall survival were 86, 35, and 18%, respectively. Five patients were alive and
      disease-free at last follow-up. Survival was associated with location of LNM.
      Specifically, 5-year overall survival was 30% among patients with LNM along the
      hepatoduodenal ligament/retropancreatic area (area 1), 14% among patients with
      LNM along the common hepatic artery/celiac axis (area 2), and there was only one
      long-term survivor who experienced recurrent disease among patients who had CLM +
      para-aortic LNM (area 3) (P = 0.004). On multivariate analyses, overall margin
      status (hazard ratio [HR] = 2.0), treated number of metastases >6 (HR = 2.3) and
      para-aortic lymph node involvement (HR = 2.6) each remained significantly
      associated with increased risk of death (all P < 0.05). CONCLUSIONS: Although
      overall survival in the setting of LNM is only 18%, certain subsets of patients
      with LNM can benefit from surgical resection. Specifically, patients with CLM +
      LNM isolated to area 1 had a 5-year survival of approximately 30%, while long
      term survival among patients with para-aortic LNM was rare.

PMID- 21743978
TI  - Is intraperitoneal chemotherapy after cytoreductive surgery efficient? Knowing
      whether it is or not appears secondary!

PMID- 21743979
TI  - Early surgical experience with minimally invasive percutaneous approach for
      patients with metastatic epidural spinal cord compression (MESCC) to poor
      prognoses.
AB  - PURPOSE: This study was designed to assess the impact of minimally invasive
      surgery (MIS) for the treatment of patients with metastatic epidural spinal cord
      compression (MESCC) and vertebral body fracture, in terms of feasibility,
      clinical improvement, and morbidity. METHODS: Twenty-five consecutive patients
      with diagnosis of MESCC from solid primary tumors were treated between January
      2008 and June 2010 at our institution. All patients, after multidisciplinary
      assessment, were considered with poor prognosis because of their disease's
      extension and/or other clinical conditions. Mini-invasive percutaneous surgery
      was performed in all patients followed by radiotherapy within 2 weeks
      postoperatively. Clinical outcome was evaluated by modified visual analog scale
      for pain, Frankel Scale for neurologic deficit, and magnetic resonance imaging or
      computed tomography scan. RESULTS: Clinical remission of pain was obtained in the
      vast majority of patients (96%). Improvement of neurological deficit was observed
      in 22 patients (88%). No major morbidity or perioperative mortality occurred. The
      average hospital stay was 6 days. Local recurrence occurred in two patients (8%).
      Median survival was 10 (range, 6-24) months. Overall survival at 1 year was 43%.
      CONCLUSIONS: For patients with MESCC and body fracture, with limited life
      expectancy, minimally invasive spinal surgery followed by radiotherapy, is
      feasible and provides clinical benefit in most of patients, with low morbidity.
      We believe that a minimally invasive approach can be an alternative surgical
      method compared with more aggressive or demanding procedures, which in selected
      patients with metastatic spinal cord compression with poor prognosis could
      represent overtreatment.

PMID- 21743980
TI  - Neoadjuvant chemotherapy increases the rate of breast conservation in lobular
      type breast cancer patients.
AB  - INTRODUCTION: Our study aims to determine whether patients with lobular-type
      breast cancer have significantly improved rates of breast conservation (BCT)
      after neoadjuvant chemotherapy (nCT). METHODS: Patients who received nCT and
      surgery within three prospective trials between 1995 and 2007 at the Medical
      University of Vienna were retrospectively analyzed. RESULTS: 325 patients had
      median follow-up of 53 months; 21% had lobular cancer, and 70% of these women
      were initially scheduled for mastectomy (MX). Twenty-one finally received BCT,
      yielding a MX-BCT turnover rate of 45%. Of patients primarily scheduled for BCT,
      20% had to finally undergo MX in lobular cancer. The 256 patients with ductal
      type breast cancer finally had a MX-BCT turnover rate of 52% (p = 0.561 versus
      lobular) and a BCT-MX turnover rate of 15% (p = 0.933 versus lobular). Secondary
      MX after initial BCT was necessary in 2% (ductal) and 10% (lobular, p = 0.110).
      There was no difference in local recurrence in lobular- as compared with ductal
      type breast cancer patients after BCT (2.7% versus 10%, p = 0.135), nor was a
      difference seen in lobular breast cancer patients when comparing BCT with MX
      (2.7% versus 3.4%, p = 0.795). Tumor type was not an independent predictor for
      either BCT or local recurrence. CONCLUSION: We do not suggest excluding patients
      with lobular-type breast cancer who are primarily scheduled for MX from nCT,
      since BCT rates may still increase by 45% without influencing the oncologic
      outcome.

PMID- 21743981
TI  - American board of surgery certificate in complex general surgical oncology: a
      reality.

PMID- 21743982
TI  - Effects of 10 days of modest intermittent hypoxia on circulating measures of
      inflammation in healthy humans.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is a common disease which is associated
      with elevated inflammatory markers and adhesion molecules, possibly due to
      nightly intermittent hypoxia (IH). The purpose of this study was to test the
      hypothesis that IH would increase systemic inflammatory markers in healthy human
      males. METHODS: Healthy, young male subjects (n = 9; 24 +/- 2 years) were exposed
      to a single daily isocapnic hypoxia exposure (oxyhemoglobin saturation = 80%, 1
      h/day) for 10 consecutive days. Serum granulocyte macrophage colony-stimulating
      factor, interferon-gamma, interleukin-1beta, interleukin-6, interleukin-8,
      leptin, monocyte chemotactic protein-1, vascular endothelial growth factor,
      intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 were
      measured before and following the 10 days of IH using Luminex. RESULTS: Nine
      subjects completed the study (24 +/- 2 years; 24 +/- 2 kg/m(2)). The mean
      oxyhemoglobin saturation was 80.8 +/- 1.6% during the hypoxia exposures. There
      was no significant change in any of the markers of inflammation (paired t test, P
      > 0.2 all cytokines). CONCLUSIONS: These findings suggest that (1) a more
      substantial or a different pattern of hypoxemia might be necessary to activate
      systemic inflammation, (2) the system may need to be primed before hypoxic
      exposure, or (3) increases in inflammatory markers in patients with OSA may be
      more related to other factors such as obesity or nocturnal arousal.

PMID- 21743983
TI  - LC-MS/MS analysis of phosphatidylethanol in dried blood spots versus conventional
      blood specimens.
AB  - Phosphatidylethanol (PEth), which is formed extrahepatically by the action of
      phospholipase D on phosphatidylcholine in the presence of ethanol, has been
      suggested as a promising marker of alcohol misuse. Analysis of dried blood spots
      (DBS) is particularly advantageous for the determination of delicate analytes
      such as PEth. Therefore, measurement of PEth species (18:1/18:1, 16:0/18:1) in
      DBS versus whole blood was performed to ascertain whether respective results are
      directly comparable. Samples were obtained from subjects (n = 40) undergoing
      alcohol detoxification treatment. Analysis involved liquid-liquid extraction from
      both, DBS and whole blood (100 MUL, respectively), with phosphatidylpropanol as
      the internal standard. Extracts were subjected to LC gradient separation using
      multiple reaction monitoring of deprotonated molecules. Results from measurements
      of corresponding DBS and whole blood specimens were compared by estimating the
      respective mean values and by a Bland and Altman analysis. Concentrations of PEth
      18:1/18:1 ranged from 46.1 to 3,360 ng/mL in whole blood (mean, 461.7 ng/mL) and
      from 35.8 to 3,360 ng/mL in DBS (mean, 457.6 ng/mL); for PEth 16:0/18:1,
      concentrations were from 900 to 213,000 ng/mL (mean, 23,375 ng/mL) and 922
      213,000 ng/mL (mean, 23,470 ng/mL) in blood and DBS, respectively. Estimated mean
      differences were -4.3 ng/mL for PEth 18:1/18:1 and 95.8 ng/mL for PEth 16:0/18:1.
      The Bland-Altman plot of both PEth species showed that the variation around the
      mean difference was similar all through the range of measured values and that all
      differences except one were within the limits of agreement. It could be shown
      that the determination of PEth species in DBS is as reliable as in whole blood
      samples. This assay may facilitate monitoring of alcohol misuse.

PMID- 21743984
TI  - Identification of organic sulfur compounds in coal bitumen obtained by different
      extraction techniques using comprehensive two-dimensional gas chromatography
      coupled to time-of-flight mass spectrometric detection.
AB  - The determination of organic sulfur compounds (OSC) in coal is of great interest.
      Technically and operationally these compounds are not easily removed and promote
      corrosion of equipment. Environmentally, the burning of sulfur compounds leads to
      the emission of SO(x) gases, which are major contributors to acid rain. Health
      wise, it is well known that these compounds have mutagenic and carcinogenic
      properties. Bitumen can be extracted from coal by different techniques, and use
      of gas chromatography coupled to mass spectrometric detection enables
      identification of compounds present in coal extracts. The OSC from three
      different bitumens were tentatively identified by use of three different
      extraction techniques: accelerated solvent extraction (ASE), ultrasonic
      extraction (UE), and supercritical-fluid extraction (SFE). Results obtained from
      one-dimensional gas chromatography (1D GC) coupled to quadrupole mass
      spectrometric detection (GC-qMS) and from two-dimensional gas chromatography with
      time-of-flight mass spectrometric detection (GC * GC-TOFMS) were compared. By use
      of 2D GC, a greater number of OSC were found in ASE bitumen than in SFE and UE
      bitumens. No OSC were identified with 1D GC-qMS, although some benzothiophenes
      and dibenzothiophenes were detected by use of EIM and SIM modes. GC * GC-TOFMS
      applied to investigation of OSC in bitumens resulted in analytical improvement,
      as more OSC classes and compounds were identified (thiols, sulfides, thiophenes,
      naphthothiophenes, benzothiophenes, and benzonaphthothiophenes). The roof-tile
      effect was observed for OSC and PAH in all bitumens. Several co-elutions among
      analytes and with matrix interferents were solved by use of GC * GC.

PMID- 21743985
TI  - Anorectal mucinous adenocarcinoma in child: a case report.
AB  - Colorectal cancer is extremely rare in children with incidence of one child per
      one million. We report an 11-year-old boy who presented with a 3-month history of
      anorexia, weight loss, vomiting with constipation and occasionally blood in
      stools. Imaging study revealed an eccentric growth in the anorectum. The patient
      underwent incision surgical biopsy, and subsequent histopathologic analysis
      revealed a mucinous adenocarcinoma of the colon. No patient follow-up was
      possible after the child left our department as he was very poor and could not
      afford the expenses of surgery or chemoradiotherapy.

PMID- 21743986
TI  - Relationship between symptoms of attention-deficit/hyperactivity disorder and
      family functioning: a community-based study.
AB  - This study examined the relationship between family functioning and attention
      deficit/hyperactivity disorder (ADHD) symptoms in an Australian community-based
      sample. Children were screened for ADHD in their second year of formal schooling.
      Two hundred and two (202) primary caregivers completed validated measures of
      family quality of life (QoL), parent mental health, parenting styles and parental
      relationship quality. Compared with controls, parents of children screening
      positive for ADHD reported poorer family QoL in the domains of emotional impact
      (mean difference [MD] -20.1; 95% CI -38.2 to -1.9, p = 0.03) and impact on family
      activities (MD -17.2; 95% CI -27.9 to -6.5, p = 0.002), less parental warmth (MD 
      3.4; 95% CI -6.0 to -0.9, p = 0.01) and higher parental depression (MD 6.8; 95%
      CI 1.8 to 11.7, p = 0.009) and anxiety (MD 6.2; 95% CI 1.7 to 10.6, p = 0.008)
      after adjusting for socio-demographic characteristics and child conduct symptoms.
      Parents of children screening positive for ADHD reported higher stress (MD 4.5;
      95% CI 1.2 to 7.1, p = 0.007) and more inconsistent (MD 3.0; 95% CI 1.2 to 4.8, p
      = 0.002) and hostile (MD = 2.2; 95% CI 1.0 to 3.4, p = 0.001) parenting after
      adjusting for socio-demographic factors only. No difference in parental
      relationship quality and parental inductive reasoning was identified. CONCLUSION:
      These findings suggest a strong association between poor family functioning and
      ADHD symptoms and carry implications for comprehensive ADHD management and the
      importance of seeing the child within the family context.

PMID- 21743987
TI  - Color duplex ultrasonography of temporal arteries: role in diagnosis and follow
      up of suspected cases of temporal arteritis.
AB  - The objectives of this study are to study the diagnostic value of color duplex
      ultrasonography (CDU) compared with the clinical results and temporal artery
      biopsy (TAB) in patients with suspected temporal arteritis (TA) and evaluate the
      prognostic value of CDU in follow-up of patients of sure diagnosis of TA under
      treatment in correlation to clinical response. The study included 32 consecutive
      patients of clinically suspected TA, and 30 age- and gender-matched control
      subjects. Baseline clinical characteristics and bilateral CDU of temporal
      arteries were performed to all subjects. CDU aimed to assess presence of a dark
      halo around the arterial lumen (a halo sign) or presence of stenoses and
      occlusions of temporal arteries. Unilateral TAB was performed then in all
      patients but not in control subjects. Subsequent CDU examinations were performed
      at 2, 4, 8, and 12 weeks after onset of treatment in patients with abnormal CDU.
      A halo sign at baseline CDU was evident in 13 TA patients (81%) and in 2 non-TA
      patients (12%) but none in control subjects. The presence of a halo sign in total
      yielded 81% sensitivity and 88% specificity whereas the presence of bilateral
      halo sign yielded 37% sensitivity and 100% specificity. Subsequent CDU
      examinations of TA patients showed disappearance of a halo sign in nine patients
      at 2 weeks and in four patients at 4 weeks with a mean of disappearance of 21
      days after initiation of treatment. CDU is non-invasive, easy, and inexpensive
      method for diagnosis of TA. It is of higher sensitivity and specificity. It can
      be used in combination with clinical and laboratory tools for diagnosis of TA. It
      can effectively predict which patient will need TAB. In patients with bilateral
      halo sign, TAB is not necessary.

PMID- 21743988
TI  - Biomonitoring fallout 137Cs in resident and migratory fishes collected along the
      southern coast of India and assessment of dose.
AB  - The globally distributed fallout radionuclide (137)Cs was monitored in 25
      resident and 22 migratory fish species collected from some regions of west and
      east coast of southern India to establish a baseline data. The samples were
      collected during June 2008 to June 2009. Higher level of (137)Cs was noted in
      planktivorous fishes and lower level in herbivores. A significant variation in
      (137)Cs was observed between fishes with different feeding habits and different
      migratory pattern. Oceanodromic migratory fishes displayed higher cesium levels
      than other migratory types. Similarly, migratory fishes displayed higher (137)Cs
      concentration compared to resident fishes. The overall range of (137)Cs varied
      from 0.06 to 0.3 Bq/kg in fishes. The biological concentration varied from 55 to
      250. The average external dose rate to fishes was calculated to be 2.7 * 10(-7)
      MUGy/h, while the internal dose rate varied from 8.50 * 10(-6) to 5.27 * 10(-5)
      MUGy/h. The hazard quotient for fishes was found to be less than 1. The average
      intake of (137)Cs via fishes to the public was calculated to be 3.5 Bq/year and
      subsequently the committed effective dose was 0.05 MUSv/year. The data obtained
      were less than global average and comparable to those of many regions.

PMID- 21743989
TI  - Hepatic mercury, cadmium, and lead in mink and otter from New York State:
      monitoring environmental contamination.
AB  - Many non-linear processes link atmospheric emissions to the bioavailability of
      metals; consequently, the monitoring of metals in ecosystem components is
      required to model their ecodynamics. American mink (Neovison vison) and river
      otter (Lontra canadensis) have the potential to serve as an upper-level-consumer
      component in monitoring metals bioavailability. However, the relationship of
      bioaccumulated metals to various environmental factors has not been explored nor
      have the effects of demographic factors been resolved. To address these
      limitations, mink and otter, collected throughout New York State during 1998
      2002, were analyzed for hepatic concentrations of total mercury (Hg), cadmium
      (Cd), and lead (Pb). Relationships were investigated between metals
      concentrations and landscape-level factors (physiographic zone, hydrologic unit,
      and elevation) and demographic factors (gender and age). Considerable variation
      in Hg and Cd concentrations was observed relative to both physiographic zone and
      hydrologic unit for both species. In contrast with Hg, Cd concentration increased
      predictably with increasing elevation. Mercury concentrations were greater, but
      for Cd less, in otter than mink. Lead concentrations showed little landscape
      heterogeneity and were independent of elevation. Age-related bioaccumulation was
      evident for Hg and Cd, but not for Pb, in both species. Mercury and Cd
      concentrations were greater in female than male mink; however, Pb concentrations
      were greater in males than females. Inverse relationships of relative growth
      (weight/length) to metals concentrations explained gender differences in Hg and
      Cd in mink. For otter, no gender-related differences in metals concentrations
      were apparent. The suitability of mink and otter for monitoring programs is
      discussed.

PMID- 21743990
TI  - Higher tacrolimus blood concentration is related to hyperlipidemia in living
      donor liver transplantation recipients.
AB  - BACKGROUND: The arrival of tacrolimus has drastically improved AALDLT recipients'
      survival. However, little data of tacrolimus have been reported concerning its
      effects on lipid metabolism for AALDLT recipients. AIM: Out aim was to
      investigate the relationship between tacrolimus blood concentration and lipid
      metabolism in AALDLT recipients. METHODS: The pre and postoperative data of 77
      adult patients receiving AALDLT between 2002 and December 2007 were
      retrospectively reviewed. The postoperative immune suppressive regimen was
      prednisone with tacrolimus +/- mycophenolate mofetil. Prednisone was withdrawn
      within the first postoperative month. Blood lipids and tacrolimus concentration
      were detected at the first, third, and sixth month during follow-up. Episodes of
      acute rejection were diagnosed based on biopsy. RESULTS: Overall prevalence of
      post-transplantation hyperlipidemia was 29.9% (23/77) at the sixth postoperative
      month. The patients were divided into two groups, the hyperlipidemia group and
      the ortholipidemia group. In the 23 patients with hyperlipidemia, 15 (65%) were
      hypercholesterolemia, five (22%) were hypertriglyceridemia, and three (13%)
      patients had both hypercholesterolemia and hypertriglyceridemia. In univariate
      analysis, only tacrolimus blood concentration at the third and sixth post
      transplantation months showed significant difference (8.7 +/- 2.1 vs. 6.9 +/-
      3.2, p = 0.013; 9.2 +/- 2.7 vs. 7.3 +/- 3.8, p = 0.038, respectively). In
      multivariate logistic analysis, only two factors appear to be risk factors,
      namely, tacrolimus blood concentration at the third and sixth post
      transplantation months (8.7 +/- 2.1 vs. 6.9 +/- 3.2, p = 0.043; 9.2 +/- 2.7 vs.
      7.3 +/- 3.8 p = 0.035, respectively). CONCLUSIONS: Higher tacrolimus blood
      concentration was related to hyperlipidemia at an early postoperative period.
      This indicates that tacrolimus blood concentration should be controlled as low as
      possible in the premise that there is no risk of rejection to minimize post
      transplant hyperlipidemia after AALDLT.

PMID- 21743991
TI  - Antiviral drug resistance testing in patients with chronic hepatitis B.
AB  - BACKGROUND: Antiviral drugs against hepatitis B virus are limited by the
      emergence of drug resistance. AIMS: We aimed to study the impact of drug
      resistance testing on treatment decisions. METHODS: In part 1 of this study,
      consecutive patients with chronic hepatitis B who had antiviral drug resistance
      testing were studied. Part 2 was a two-step questionnaire survey including ten
      characteristic case scenarios. Hepatologists were asked about their treatment
      decisions before and after the knowledge of drug resistance results. RESULTS:
      Fifty-one patients underwent drug resistance testing, most of whom were on
      lamivudine, adefovir dipivoxil or entecavir monotherapy. Thirty-four (67%)
      patients had drug-resistant mutants detected, 4 (8%) had low viral load, and 13
      (25%) harboured wild-type virus. Twenty-nine of 34 (85%) patients harbouring drug
      resistant mutants and 9 of 17 (53%) patients with no mutants detected changed
      their drug regimens (P = 0.038). In part 2, 18 hepatologists completed all two
      questionnaires. Overall, treatment decision was modified in 52% of cases upon
      receiving the drug resistance testing results. The detection of rtA181V/I
      resulted in decision changes in most hepatologists, with the preferred treatment
      switching from tenofovir to entecavir. When no mutants were detected in partial
      responders to entecavir monotherapy, most hepatologists chose to increase the
      dose of entecavir. CONCLUSIONS: Drug-resistant mutations are detected in around
      two-thirds of chronic hepatitis B patients undergoing drug resistance testing.
      Drug resistance testing alters management in over half of the cases, and should
      be considered in all patients with virological breakthrough and suboptimal
      virological suppression.

PMID- 21743992
TI  - The Tullio phenomenon: a neurologically neglected presentation.
AB  - The Tullio phenomenon refers to sound-induced disequilibrium or oscillopsia.
      Patients with this condition frequently present to neurologists, many of whom are
      unfamiliar with the condition and its diagnostic criteria. Indeed, due to the
      unusual nature of the symptoms patients are often misdiagnosed as having
      psychiatric disturbances. Tullio patients describe disequilibrium, auditory and
      visual symptoms, which are recurrent, brief, and often triggered by loud noises
      or middle ear pressure changes, e.g. the Valsalva manoeuvre. Many cases are
      associated with superior semicircular canal dehiscence (SCCD). Early work
      suggested that the presence of sound-induced torsional eye movements and visual
      field tilts were consequent upon a utricular-mediated ocular tilt reaction.
      However, more recent evidence from imaging and oculographic research, as well as
      data from our patient series indicates that these ocular abnormalities are
      usually the result of superior semicircular canal stimulation. The clinical
      history and a focussed examination are often sufficient to make the diagnosis,
      which can be confirmed with high resolution CT imaging of the temporal bones. In
      some patients, surgical occlusion or resurfacing of the affected canal can
      ameliorate symptoms and signs. The aim of this paper is two-fold: Firstly, to
      review the clinical features of the Tullio phenomenon, and secondly, to highlight
      our own observations in three cases with a new clinical syndrome consisting of
      Tullio's phenomenon with bilateral vestibular failure, a pure horizontal
      nystagmus in response to sound, and no evidence of canal dehiscence.

PMID- 21743993
TI  - Expression, characterization and 2,4,6-trichlorophenol degradation of laccase
      from Monilinia fructigena.
AB  - A novel laccase gene from Monilinia fructigena was synthesized chemically
      according to the yeast bias codon and integrated into the genome of Pichia
      pastoris GS115 by electroporation. The expressed enzyme was recovered from the
      culture supernatant and purified. The result of enzyme activity assay and SDS
      PAGE demonstrated that the recombinant laccase was induced and extracellularly
      expressed in P. pastoris. Main biochemical properties of this laccase, such as
      thermodependence and thermostability, optimal pH and pH stability, and the effect
      of metal ions and inhibitors, were characterized. With 2,2'-azinobis-(3
      ethylbenzothiazoline-6-sulfonate (ABTS) as the substrate, MfLcc had its optimal
      pH at 3.5 and optimal temperature at 45 degrees C. The Km values of the ABTS,
      guaiacol were 0.012 and 0.016 Mm, respectively, and the corresponding V (max)
      values are 243.9 and 10.55 Um min(-1) mg(-1), respectively. The recombinant
      laccase degraded 80% 2,4,6-trichlorophenol after 8 h under the optimal
      conditions. The recombinant strain and its laccase can be considered as candidate
      for treating waste water polluted with trichlorophenols.

PMID- 21743994
TI  - Analysis of gene expression profile of Arabidopsis genes under trichloroethylene
      stresses with the use of a full-length cDNA microarray.
AB  - Trichloroethylene (TCE) is a widespread and persistent environmental contaminant.
      Plants are able to take up a range of harmful organic compounds, including some
      of the most abundant environmental pollutants like TCE. In this study,
      complementary DNA microarrays were constructed to have a better view of
      transcript expression in Arabidopsis thaliana during TCE-induced stress. The
      microarray analysis demonstrated the complexity of gene expression patterns
      resulting from TCE. A total of 1,020 transcripts were differentially up-regulated
      by TCE. Those genes might specifically contribute to the TCE transformation,
      conjugation, and compartmentation in plant. This study provides informative
      preliminary data for more in-depth analyses of TCE tolerance in Arabidopsis
      thaliana.

PMID- 21743995
TI  - A promoter polymorphism of MSTN g.-371T>A and its associations with carcass
      traits in Korean cattle.
AB  - A promoter polymorphism of bovine Myostatin (MSTN) gene g.-371T>A was screened in
      Holstein and two Korean indigenous cattle breeds, Hanwoo and Jeju Black cattle
      (JBC). The MSTN g.-371T>A polymorphism was found in all three cattle breeds
      tested. An allele MSTN g.-371A was the most frequent in the JBC breed among
      breeds tested. The association of MSTN genotypes for carcass traits was also
      tested in the Hanwoo population. Significant differences were found between the
      genotypes and level of meat quality grade index which converted the marbling
      score levels (P < 0.05), reflecting the metabolic role of MSTN for inhibition of
      preadipocyte differentiation in intramuscular fat deposition. In addition,
      significant differences were found for fat color index of backfat according to
      MSTN genotypes (P < 0.05), suggesting that MSTN may play a role in deposition of
      white-yellow adipocytes in backfat. However, there was no detection of
      significant association of genotypes with the live weight, carcass weight,
      backfat thickness, eye muscle area, marbling score, or meat color index (P >
      0.05). Despite the lack of statistical association, wild type g.-371T/-showed
      association patterns similar to those of A/A homozygotes, such as heavier
      weights, thinner backfat, larger eye muscle area, and lower marbling score. The
      results of the present study suggest that MSTN promoter polymorphism g.-371T>A
      may affect carcass traits, which could be a useful molecular marker for planning
      improvements in the economic traits of Korean cattle breeds.

PMID- 21743996
TI  - Sentinel lymph node biopsy compared with axillary lymph node dissection in early
      breast cancer: a meta-analysis.
AB  - Sentinel lymph node biopsy (SLNB) has been recommended as the standard
      performance for negative sentinel lymph node (SLN) patients without axillary
      lymph node dissection (ALND) in the surgical management of early breast cancer;
      however, the efficiency of SLNB for patients with positive SLNs is still unclear.
      We performed this meta-analysis to compare the effectiveness and safety of SLNB
      with ALND. Randomized controlled trials (RCTs) comparing SLNB with ALND in early
      breast cancer were identified in Pubmed, Embase, and The Cochrane Library.
      Overall survival (OS), disease-free survival (DFS), regional lymph node
      recurrence, postoperative morbidity, and quality of life (QOL) between the two
      groups were assessed by using the methods provided by the Cochrane Handbook for
      Systematic Reviews of Interventions. Eight well-designed RCTs (total 8,560
      patients; 4,301 for SLNB and 4,259 for ALND) were included. Meta-analysis showed
      that there was no statistical difference in OS (HR = 1.07, 95% CI: 0.90-1.27),
      DFS (HR = 1.00, 95% CI: 0.88-1.14), and regional lymph node recurrence (OR =
      1.65, 95% CI: 0.77-3.56) between SLNB and ALND group, whether for SLN (+)
      subgroup or for SLN (-) subgroup. However, SLNB results in a significant
      reduction of postoperative morbidity and improved QOL. In conclusion, SLNB can be
      recommended as preferred care for SLN-negative patients and selected patients
      with SLN-micrometastasis. Despite this, ALND remains the standard management in
      breast cancer patients with SLN-macrometastasis.

PMID- 21743997
TI  - Diffusion-weighted imaging in acute demyelinating myelopathy.
AB  - INTRODUCTION: Diffusion-weighted imaging (DWI) has become a reference MRI
      technique for the evaluation of neurological disorders. Few publications have
      investigated the application of DWI for inflammatory demyelinating lesions. The
      purpose of the study was to describe diffusion-weighted imaging characteristics
      of acute, spinal demyelinating lesions. METHODS: Six consecutive patients (two
      males, four females; aged 28-64 years) with acute spinal cord demyelinating
      lesions were studied in a prospective case series design from June 2009 to
      October 2010. We performed magnetic resonance imaging studies from 2 to 14 days
      from symptom onset on the patients with relapsing remitting multiple sclerosis (n
      = 3) or clinically isolated syndrome (n = 3). Main outcome measures were
      diffusion-weighted imaging and apparent diffusion coefficient pattern (ADC) of
      acute spinal cord demyelinating lesions. RESULTS: All spinal lesions showed a
      restricted diffusion pattern (DWI+/ADC-) with a 24% median ADC signal decrease. A
      good correlation between clinical presentation and lesion site was observed.
      CONCLUSION: Acute demyelinating spinal cord lesions show a uniform restricted
      diffusion pattern. Clinicians and neuro-radiologists should be aware that this
      pattern is not necessarily confirmatory for an ischaemic aetiology.

PMID- 21743998
TI  - Effects of physical culture parameters on bacteriocin production by Mexican
      strains of Bacillus thuringiensis after cellular induction.
AB  - We have shown previously that in the presence of inducer Bacillus cereus 183,
      significant increases in bacteriocin production and bactericidal activity of B.
      thuringiensis occur when the latter is cultivated at pH 7.2, 28 degrees C, and
      180 rpm. Here we show that this activity can be further improved when B.
      thuringiensis is induced with B. cereus 183 and then cultivated with modification
      of pH, temperature, and agitation. Five native strains of B. thuringiensis, LBIT
      269, LBIT 287, LBIT 404, LBIT 420, and LBIT 524 which synthesize, respectively,
      morricin 269, kurstacin 287, kenyacin 404, entomocin 420, and tolworthcin 524,
      were cultivated in four different fermentation media. Of these, fermentation in
      tryptic soy broth (TSB) yielded the highest level of bacteriocin activity (~100
      133 FU). Bacteria grown in TSB were induced with B. cereus 183 and cultivated at
      different pH (6.0, 7.2, 8.0), temperature (26, 28, 30 degrees C), and agitation
      (150, 180, 210 rpm). Full factorial design was performed and results were
      analyzed with analysis of variance (ANOVA) and Tukey multiple comparison tests at
      significant level of alpha <= 0.05 to study the influence of the three variables
      on bacterial growth and bacteriocin production. Our data show that the highest
      bacteriocin activity was found with LBIT 269 and LBIT 404 with an increase of ~95
      100% compared with induced B. thuringiensis strains cultivated under fixed
      conditions (pH 7.2, 28 degrees C, 180 rpm), for which the data were set at 0%.
      The optimal conditions for morricin 269 and kenyacin 404 production were,
      respectively, pH 8, 30 degrees C, 210 rpm and pH 7.2, 26 degrees C, 210 rpm.

PMID- 21743999
TI  - Spatial patterns of mercury in macroinvertebrates and fishes from streams of two
      contrasting forested landscapes in the eastern United States.
AB  - Controls on mercury bioaccumulation in lotic ecosystems are not well understood.
      During 2007-2009, we studied mercury and stable isotope spatial patterns of
      macroinvertebrates and fishes from two medium-sized (<80 km(2)) forested basins
      in contrasting settings. Samples were collected seasonally from multiple sites
      across the Fishing Brook basin (FB(NY)), in New York's Adirondack Mountains, and
      the McTier Creek basin (MC(SC)), in South Carolina's Coastal Plain. Mean
      methylmercury (MeHg) concentrations within macroinvertebrate feeding groups, and
      mean total mercury (THg) concentrations within most fish feeding groups were
      similar between the two regions. However, mean THg concentrations in game fish
      and forage fish, overall, were much lower in FB(NY) (1300 and 590 ng/g dw,
      respectively) than in MC(SC) (2300 and 780 ng/g dw, respectively), due to lower
      trophic positions of these groups from FB(NY) (means 3.3 and 2.7, respectively)
      than MC(SC) (means 3.7 and 3.3, respectively). Much larger spatial variation in
      topography and water chemistry across FB(NY) contributed to greater spatial
      variation in biotic Hg and positive correlations with dissolved MeHg and organic
      carbon in streamwater. Hydrologic transport distance (HTD) was negatively
      correlated with biotic Hg across FB(NY), and was a better predictor than wetland
      density. The small range of landscape conditions across MC(SC) resulted in no
      consistent spatial patterns, and no discernable correspondence with local-scale
      environmental factors. This study demonstrates the importance of local-scale
      environmental factors to mercury bioaccumulation in topographically heterogeneous
      landscapes, and provides evidence that food-chain length can be an important
      predictor of broad-scale differences in Hg bioaccumulation among streams.

PMID- 21744000
TI  - Identification of amino acids in highly pathogenic avian influenza H5N1 virus
      hemagglutinin that determine avian influenza species specificity.
AB  - To test the role of neutralizing antibodies (nAbs) and receptor adaptation in
      interspecies transmission of influenza virus, two H5N1 strains, isolated from
      human and avian hosts, with four amino acid differences in hemagglutinin (HA) and
      seven HA mutations were studied. We found that a mutation at amino acid position
      90 in the H5N1 HA, outside the receptor-binding domain (RBD), could
      simultaneously induce changes in the RBD conformation to escape from nAb binding
      and alter the receptor preference through long-range regulation. This mutation
      was deemed a "key event" for interspecies transmission. It is likely a result of
      positive selection caused by antibodies, allowing the original invasion by new
      species-specific variants. A mutation at amino acid position 160 in the RBD only
      induced a change in receptor preference. This mutation was deemed a "maintaining
      adaptation", which ensured that influenza virus variants would be able to infect
      new organisms of a different species successfully. The mutation is the result of
      adaptation caused by the receptor. Our results suggest that continuing occurrence
      of these two types of mutations made the variants persist in the new host
      species.

PMID- 21744001
TI  - Indigenous and introduced potyviruses of legumes and Passiflora spp. from
      Australia: biological properties and comparison of coat protein nucleotide
      sequences.
AB  - Five Australian potyviruses, passion fruit woodiness virus (PWV), passiflora
      mosaic virus (PaMV), passiflora virus Y, clitoria chlorosis virus (ClCV) and
      hardenbergia mosaic virus (HarMV), and two introduced potyviruses, bean common
      mosaic virus (BCMV) and cowpea aphid-borne mosaic virus (CAbMV), were detected in
      nine wild or cultivated Passiflora and legume species growing in tropical,
      subtropical or Mediterranean climatic regions of Western Australia. When ClCV
      (1), PaMV (1), PaVY (8) and PWV (5) isolates were inoculated to 15 plant species,
      PWV and two PaVY P. foetida isolates infected P. edulis and P. caerulea readily
      but legumes only occasionally. Another PaVY P. foetida isolate resembled five
      PaVY legume isolates in infecting legumes readily but not infecting P. edulis.
      PaMV resembled PaVY legume isolates in legumes but also infected P. edulis. ClCV
      did not infect P. edulis or P. caerulea and behaved differently from PaVY legume
      isolates and PaMV when inoculated to two legume species. When complete coat
      protein (CP) nucleotide (nt) sequences of 33 new isolates were compared with 41
      others, PWV (8), HarMV (4), PaMV (1) and ClCV (1) were within a large group of
      Australian isolates, while PaVY (14), CAbMV (1) and BCMV (3) isolates were in
      three other groups. Variation among PWV and PaVY isolates was sufficient for
      division into four clades each (I-IV). A variable block of 56 amino acid residues
      at the N-terminal region of the CPs of PaMV and ClCV distinguished them from PWV.
      Comparison of PWV, PaMV and ClCV CP sequences showed that nt identities were both
      above and below the 76-77% potyvirus species threshold level. This research gives
      insights into invasion of new hosts by potyviruses at the natural vegetation and
      cultivated area interface, and illustrates the potential of indigenous viruses to
      emerge to infect introduced plants.

PMID- 21744002
TI  - Morphology, cytogenetics, and survival in myelodysplasia with del(20q) or
      ider(20q): a multicenter study.
AB  - Isochromosome of the long arm of chromosome 20 with interstitial loss of material
      [ider(20q)] is a rare cytogenetic abnormality reported in myelodysplastic
      syndrome (MDS), with neither specific morphological pattern nor clear prognostic
      significance. The aim of this retrospective multicentric study is to compare the
      peripheral blood and bone marrow morphology of MDS patients with ider(20q) (n =
      13) and del(20q) (n = 21) and controls (n = 47) in order to investigate whether
      the ider(20q) harbors specific morphological features. The secondary objective is
      to compare the outcome of patients from both groups. This study performed on the
      largest cohort of MDS patients with ider(20q) is the first that identifies
      specific morphological features (hypogranulated and vacuolized neutrophils and
      neutrophil erythrophagocytosis) allowing the identification of this cytogenetic
      abnormality with high sensitivity (70%) and specificity (85.7%). Suspected
      ider(20q) by morphology should therefore support targeted FISH tests in case of
      non informative karyotype. This combined approach will allow a better estimation
      of the prevalence of this underdiagnozed entity. The overall survival and
      progression-free survival did not statistically differ in both groups. However,
      hypogranulated and vacuolized neutrophils were significantly associated with
      survival.

PMID- 21744003
TI  - Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal
      karyotype AML (NK-AML).
AB  - Prognosis of AML in elderly patients is poor due to adverse patient
      characteristics and comorbidities. In addition, disease-associated parameters
      reveal differences between older and younger patients with AML. Survival in
      normal karyotype AML (NK-AML) is influenced by different clinical and molecular
      markers. The aim of this work was to investigate the frequencies of molecular
      markers in patients with NK-AML with a focus on NPM1 mutations and FLT3-ITD in
      different age groups. In the present study, we analyzed the frequencies of
      mutations of NPM1 and FLT3-ITD in a cohort of 1,321 adult patients and 148
      children with AML treated within the AMLCG99, the AML98, and AML04 trials and
      their distribution in different age groups. Additionally, the frequencies of
      mutations in CEBPA genes, FLT3-TKD, and MLL-PTD were analyzed in the cohort with
      NK-AML (n = 729). Our data show that the presence of mutations of NPM1 (from 60%
      to 40%) and FLT3-ITD (from 50% to 20%) significantly decreased with age in adult
      AML. Consequently, the proportion of NPM1-/FLT3-ITD- patients increased with age.
      The decreasing frequency of NPM1 mutations in elderly patients was paralleled by
      a reduced complete remission (CR) rate in the elderly of 55% compared to 80% in
      the younger patients. By contrast, the frequencies of other gene mutations, like
      FLT3-TKD and MLL-PTD, and mutations in CEBPA were not age-dependent. The
      decreasing frequency of the favorable NPM1 mutations with increasing age may
      partially explain the worse outcome in the elderly patients. Furthermore, the
      increasing amount of elderly patients without NPM1 mutations or FLT3-ITD suggests
      that other molecular and clinical risk factors may influence prognosis in this
      age group.

PMID- 21744004
TI  - Methamphetamine and HIV-1 Tat down regulate beta-catenin signaling: implications
      for methampetamine abuse and HIV-1 co-morbidity.
AB  - Methamphetamine (Meth) abuse exacerbates HIV-1-associated neurocognitive
      disorders (HAND). The underlying mechanism for this effect is not entirely clear
      but likely involves cooperation between Meth and HIV-1 virotoxins, such as the
      transactivator of transcription, Tat. HIV-1 Tat mediates damage in the CNS by
      inducing inflammatory processes including astrogliosis. Wnt/beta-catenin
      signaling regulates survival processes for both neurons and astrocytes. Here, we
      evaluated the impact of Meth on the Wnt/beta-catenin pathway in astrocytes
      transfected with Tat. Meth and Tat downregulated Wnt/beta-catenin signaling by
      >50%, as measured by TOPflash reporter activity in both an astrocytoma cell line
      and primary human fetal astrocytes. Meth and Tat also downregulated LEF-1
      transcript by >30%. LEF-1 is a key partner of beta-catenin to regulate cognate
      gene expression. Interestingly, estrogen, which induces beta-catenin signaling in
      a cell-type specific manner, at physiological concentrations of 1.5 and 3 nM
      normalized individual Meth and Tat effects on beta-catenin signaling but not
      their combined effects. These findings suggest that Meth and Tat likely exert
      different mechanisms to mediate down regulation of beta-catenin signaling. The
      consequences of which may contribute to the pathophysiologic effects of HIV-1 and
      Meth co-morbidity in the CNS.

PMID- 21744005
TI  - Energy expenditure during 2-day trail walking in the mountains (2,857 m) and the
      effects of amino acid supplementation in older men and women.
AB  - We compared relative exercise intensity and active energy expenditure (AEE) on
      trail walking in the mountains, with those of daily exercise training, and
      whether branched-chain amino acid (BCAA) and arginine supplementation attenuated
      the release of markers indicating muscle damage and declines in physical
      performance. Twenty-one subjects (~63 years) were divided into two groups: amino
      acid (AA, 51 g of amino acids and 40 g of carbohydrate, male/female = 6/4) or
      placebo (PL, 91 g of carbohydrate, male/female = 6/5) supplementation during 2
      days of trail walking in the mountains. We measured heart rate (HR), AEE, fatigue
      sensation, water and food intake, and sweat loss during walking. In addition, we
      measured peak aerobic capacity [Formula: see text] and heart rate (HR(peak)) with
      graded-intensity walking, vertical jumping height (VJ) before and after walking.
      We found that average HR and AEE during uphill walking were ~100% HR(peak) and
      ~60% [Formula: see text], while they were ~80 and ~20% during downhill walking,
      respectively. Moreover, average total AEE per day was sevenfold that of their
      daily walking training. VJ after walking remained unchanged compared with the
      baseline in AA (P > 0.2), while it was reduced by ~10% in PL (P < 0.01), although
      with no significant difference in the reduction between the groups (P > 0.4). The
      responses of other variables were not significantly different between groups
      (all, P > 0.2). Thus, trail walking in the mountains required a high-intensity
      effort for older people, while the effects of BCAA and arginine supplementation
      were modest in this condition.

PMID- 21744006
TI  - Comparative analysis of placental vasculature and placental volume in normal and
      IUGR pregnancies with the use of three-dimensional Power Doppler.
AB  - OBJECTIVES: To evaluate the differences in placental vascular indices and
      placental volume between normal and IUGR pregnancies. METHODS: A prospective
      study was conducted on a group of 100 normal and 20 IUGR pregnancies between 22
      and 42 weeks of gestation. For the purpose of evaluation of placental volume and
      placental vascular indices, we applied 3D Power Doppler and VOCAL technique. Only
      patients with entirely visualized placenta were included in the study. RESULTS: A
      comparative analysis of vascularization index (VI), vascularization flow index
      (VFI), flow index (FI), and placental volume (PV) revealed statistically
      significant differences between normal and IUGR pregnancies. In normal
      pregnancies, the volume of the placenta was on average 92.42 cm(3) larger than in
      pregnancies complicated by IUGR. Receiver operating characteristic (ROC) curves
      were used to evaluate the clinical usefulness of placental vascular indices and
      placental volume for discriminating IUGR and normal pregnancies. It was concluded
      that the VI, VFI, PV, FI parameters are the best discriminants, with the cut-off
      values of 5.30, 2.30, 199, and 36.0, respectively. CONCLUSIONS: The quantitative
      assessment of placental vasculature and placental volume by means of 3D Power
      Doppler and VOCAL technique is an adjunctive modality for differentiation between
      normal and IUGR pregnancies. Our findings further suggest that the
      vascularization index (VI) and vascularization flow index (VFI) are the best
      parameters with the most favorable discriminating potential for proper
      identification of IUGR pregnancies.

PMID- 21744007
TI  - Variations in suppressor molecule ctla-4 gene are related to susceptibility to
      multiple myeloma in a polish population.
AB  - Various phenotype and functional T-cell abnormalities are observed in multiple
      myeloma (MM) patients. The aim of this study was to investigate the association
      between polymorphisms in the gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA
      4), a negative regulator of the T-lymphocyte immune response and susceptibility
      to multiple myeloma in a Polish population. Two hundred MM patients and 380
      healthy subjects were genotyped for the following polymorphisms: CTLA-4c.49A>G,
      CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA
      4g.*10223G>T). Our study is the largest and most comprehensive evaluation to date
      of the association between genetic polymorphisms in the CTLA-4 molecule and
      multiple myeloma. It was found that CTLA-4c.49A>G[G], CT60[G], and Jo31[G]
      alleles were more frequently observed in MM patients than in controls (0.50 vs.
      0.44, p = 0.03, 0.65 vs. 0.58, p = 0.04, and 0.63 vs. 0.57, p = 0.03,
      respectively). Moreover, the haplotype CTLA-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA
      4g.*642AT(8_33) [8], CT60[G], Jo31[G] including all susceptibility alleles
      increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08-6.89, p =
      0.00001). These findings indicate that genetic variations in the CTLA-4 gene play
      role in susceptibility to multiple myeloma and warrant further investigation
      through replication studies.

PMID- 21744008
TI  - The scotopic electroretinogram of the sugar glider related to histological
      features of its retina.
AB  - The flash electroretinogram (ERG) was used to characterize the scotopic retinal
      function in a marsupial. Key parameter values of the a- and b-waves of adult male
      sugar gliders, Petaurus breviceps breviceps, elicited with ganzfeld flashes were
      determined under dark- and light-adapted conditions. Using standard histological
      methods, the thicknesses of the major layers of the retina were assessed to
      provide insight into the nature of the ERG responses. The ERG and histological
      results were compared to corresponding data for placental C57Bl/6 mice to
      establish whether the functional retinal specialization that underlies scotopic
      visual function in a marsupial parallels that of a placental mouse. The
      sensitivity of the a-wave assessed with the Lamb and Pugh (Invest Ophthalmol Vis
      Sci 47:5138-5152, 2006) "model" and that of the b-wave assessed with standard
      methods were lower in the sugar glider compared to the mouse. The thickness of
      the sugar glider retina was two-third of that of the mouse. The high-intensity
      flash ERG of the sugar glider substantially differed in shape from that of the
      mouse reflecting perhaps structural and functional differences between the two
      species at the level of the inner retina.

PMID- 21744009
TI  - Spatial reflection patterns of iridescent wings of male pierid butterflies:
      curved scales reflect at a wider angle than flat scales.
AB  - The males of many pierid butterflies have iridescent wings, which presumably
      function in intraspecific communication. The iridescence is due to nanostructured
      ridges of the cover scales. We have studied the iridescence in the males of a few
      members of Coliadinae, Gonepteryx aspasia, G. cleopatra, G. rhamni, and Colias
      croceus, and in two members of the Colotis group, Hebomoia glaucippe and Colotis
      regina. Imaging scatterometry demonstrated that the pigmentary colouration is
      diffuse whereas the structural colouration creates a directional, line-shaped far
      field radiation pattern. Angle-dependent reflectance measurements demonstrated
      that the directional iridescence distinctly varies among closely related species.
      The species-dependent scale curvature determines the spatial properties of the
      wing iridescence. Narrow beam illumination of flat scales results in a narrow far
      field iridescence pattern, but curved scales produce broadened patterns. The
      restricted spatial visibility of iridescence presumably plays a role in
      intraspecific signalling.

PMID- 21744010
TI  - Large odorous frogs (Odorrana graminea) produce ultrasonic calls.
AB  - We present the first data on the vocalizations of large odorous frogs (Odorrana
      graminea, previously Odorrana livida), from southern China. The males produce
      diverse broadband signals most of which contain ultrasonic harmonics. Six basic
      call-types were identified based on the number of call notes, fundamental
      frequency, call/note duration, frequency modulation patterns and spectral
      composition. O. graminea is one of only a few non-mammalian vertebrates able to
      detect ultrasound, but its tympanic membranes are not recessed. These results
      should stimulate further studies to provide new insights into the mechanisms
      underlying high-frequency communication in anurans.

PMID- 21744011
TI  - Creatine but not betaine supplementation increases muscle phosphorylcreatine
      content and strength performance.
AB  - We aimed to investigate the role of betaine supplementation on muscle
      phosphorylcreatine (PCr) content and strength performance in untrained subjects.
      Additionally, we compared the ergogenic and physiological responses to betaine
      versus creatine supplementation. Finally, we also tested the possible additive
      effects of creatine and betaine supplementation. This was a double-blind,
      randomized, placebo-controlled study. Subjects were assigned to receive betaine
      (BET; 2 g/day), creatine (CR; 20 g/day), betaine plus creatine (BET+CR; 2+20
      g/day, respectively) or placebo (PL). At baseline and after 10 days of
      supplementation, we assessed muscle strength and power, muscle PCr content, and
      body composition. The CR and BET+CR groups presented greater increase in muscle
      PCr content than PL (p=0.004 and p=0.006, respectively). PCr content was
      comparable between BET versus PL (p=0.78) and CR versus BET+CR (p=0.99). CR and
      BET+CR presented greater muscle power output than PL in the squat exercise
      following supplementation (p=0.003 and p=0.041, respectively). Similarly, bench
      press average power was significantly greater for the CR-supplemented groups. CR
      and BET+CR groups also showed significant pre- to post-test increase in 1-RM
      squat and bench press (CR: p=0.027 and p<0.0001; BET+CR: p=0.03 and p<0.0001 for
      upper- and lower-body assessments, respectively) No significant differences for 1
      RM strength and power were observed between BET versus PL and CR versus BET+CR.
      Body composition did not differ between the groups. In conclusion, we reported
      that betaine supplementation does not augment muscle PCr content. Furthermore, we
      showed that betaine supplementation combined or not with creatine supplementation
      does not affect strength and power performance in untrained subjects.

PMID- 21744012
TI  - Delta1-pyrroline-5-carboxylate reductase as a new target for therapeutics:
      inhibition of the enzyme from Streptococcus pyogenes and effects in vivo.
AB  - Compounds able to interfere with amino acid biosynthesis have the potential to
      inhibit cell growth. In both prokaryotic and eukaryotic microorganisms, unless an
      ornithine cyclodeaminase is present, the activity of delta1-pyrroline-5
      carboxylate (P5C) reductase is mandatory to proline production, and the enzyme
      inhibition should result in amino acid starvation, blocking in turn protein
      synthesis. The ability of some substituted derivatives of
      aminomethylenebisphosphonic acid and its analogues to interfere with the activity
      of the enzyme from the human pathogen Streptococcus pyogenes was investigated.
      Several compounds were able to suppress activity in the micromolar range of
      concentrations, with a mechanism of uncompetitive type with respect to the
      substrate P5C and non-competitive with respect to the electron donor NAD(P)H. The
      actual occurrence of enzyme inhibition in vivo was supported by the effects of
      the most active derivatives upon bacterial growth and free amino acid content.

PMID- 21744013
TI  - Amino Acids Glycation Section.

PMID- 21744014
TI  - Two-dimensional lattice Boltzmann study of red blood cell motion through
      microvascular bifurcation: cell deformability and suspending viscosity effects.
AB  - Red blood cell (RBC) motion and trajectories in bifurcated microvessels are
      simulated using a two-dimensional immersed boundary-lattice Boltzmann method (IB
      LBM). A RBC is modeled as a capsule with viscous interior fluid enclosed by a
      flexible membrane. For the symmetric bifurcation model employed, the critical
      offset position in the mother branch, which separates the RBC flux toward the two
      branches, has been calculated. The RBC flux and the hematocrit partitioning
      between the two daughter branches have also been studied. Effects of the flow
      rate ratio, cell deformability and suspending viscosity have been examined.
      Simulation results indicate that increased cell rigidity and suspending viscosity
      have counter effects on cell trajectory through a bifurcation: the cell
      trajectory shifts toward the low flow-rate branch for less deformable cells, and
      toward the high flow-rate branch for more viscous plasma. These results imply
      that a higher cell rigidity would reduce the regular phase separation of
      hematocrit and plasma skimming processes in microcirculation, while an increased
      viscosity has the opposite effect. This has implications for relevant studies in
      fundamental biology and biomedical applications.

PMID- 21744015
TI  - Hypo-elastic model for lung parenchyma.
AB  - A simple, isotropic, elastic constitutive model for the spongy tissue in lung is
      formulated from the theory of hypo-elasticity. The model is shown to exhibit a
      pressure dependent behavior that has been interpreted in the literature as
      indicating extensional anisotropy. In contrast, we show that this behavior arises
      naturally from an analysis of isotropic hypo-elastic invariants and is a result
      of non-linearity, not anisotropy. The response of the model is determined
      analytically for several boundary value problems used for material
      characterization. These responses give insight into both the material behavior as
      well as admissible bounds on parameters. The model predictions are compared with
      published experimental data for dog lung.

PMID- 21744016
TI  - Effects of a neem seed extract (MiteStop(r)) on mallophages (featherlings) of
      chicken: in vivo and in vitro studies.
AB  - Mallophages of birds (featherlings) are mostly very tiny and can even as adults
      better be recognized by their movements than by their elongate body shape when
      using just the naked eye. Since some species (e.g., the "shaft louse" Menopon
      gallinae, the elongate feather louse Lipeurus caponis, or Columbicola sp.) may
      pierce the pulp of feathers or the skin by their biting or scratching mandibles
      and thus lick the excreted blood, they may be extremely dangerous especially to
      young birds, even if they only feed by nibbling along the feather surface and/or
      eat epidermal debris. The present paper reports on the successful treatment of
      different races of fowls being severely infested with both above cited species.
      This in vivo treatment was done either by a short dipping of the whole fowl into
      the 1:33 dilution (with tap water) of a neem seed extract (MiteStop(r)) or by
      spraying them with the freshly diluted product. It was seen that the dead
      mallophages dropped down from the feathers as soon as they were dry again. As a
      precaution, a second treatment was done by some owners 1 week after the first one
      in order to eliminate all stages, which eventually might have hatched from
      untouched nits during the time interval between the two treatments. When
      controlling the treated fowls 4 weeks after the treatment, in no case (treated
      once or twice), living motile stages were diagnosed indicating the high efficacy
      of this nontoxic neem seed extract. When treating in vitro cutoff feathers
      contaminated with L. caponis, it was seen under the stereomicroscope, that the
      mallophages tried to run away from the 1:33 water-diluted active compound
      indicating that there is also a repellent effect. Treated L. caponis stopped leg
      movements within 3 min and died on their feathers within 1-20 min. Then, the last
      slight trembling movements of their legs and convulsions of their intestine
      stopped finally.

PMID- 21744017
TI  - Molecular characterization of Cryptosporidium in children in Oyo State, Nigeria:
      implications for infection sources.
AB  - A study was conducted to detect and identify Cryptosporidium spp. in 43 children
      from Oyo State, Nigeria. Using nested polymerase chain reaction, 11.6% of the
      children were identified as positive for Cryptosporidium spp. Restriction
      fragment length polymorphism analysis and DNA sequencing of the PCR products
      showed the presence of three subtype families of Cryptosporidium hominis (two
      isolates of Ia and one isolate of Ib) and Cryptosporidium parvum (two isolates of
      IIc), all anthroponotic in nature. This study identified a high diversity of
      Cryptosporidium subtypes and clearly suggested that anthroponotic rather than
      zoonotic transmission played a more important role in the epidemiology of
      Cryptosporidium in the studied area.

PMID- 21744018
TI  - Occurrence of Cryptosporidium spp. in red foxes and brown bear in the Slovak
      Republic.
AB  - Wild animals can be involved in epidemiology of many important diseases and often
      act as reservoirs of pathogens which cause disease in domestic animals and
      humans. This paper aims the role of red fox (Vulpes vulpes) and brown bear (Ursus
      arctos) in the circulation of coccidian parasites from the genus Cryptosporidium.
      Cryptosporidiosis is known as an important enteric pathogen, clinical symptoms in
      particular in immune-compromised individuals range from mild to severe diarrhoea
      and dehydration, which could be fatal. Fecal samples from 62 red foxes shot
      during September 2010 to February 2011 and 63 brown bears collected during June
      2010 to March 2011 in central and eastern Slovakia were examined for the
      qualitative determination of Cryptosporidium spp. antigens in faeces by sandwich
      ELISA kit. Overall, 38.7% (24/62) of faecal samples of red foxes and 55.6%
      (35/63) of faecal samples of brown bear were positive. Our preliminary results
      emphasize prevalence of Cryptosporidium spp. amongst brown bears and red foxes in
      Slovakia and highlight the potential risk for transmission of cryptosporidiosis
      to humans using the countryside for professional or recreational purposes.

PMID- 21744019
TI  - Ultrastructural changes in the advanced third larval stage of Gnathostoma
      binucleatum Almeyda-Artigas, 1991 (Nematoda: Spirurida) following albendazole and
      albendazole sulfoxide in vitro exposure.
AB  - We report here the ultrastructural changes in the third advanced larval stage
      (AL3) of Gnathostoma binucleatum Almeyda-Artigas, 1991, induced by in vitro
      treatment with albendazole and the metabolite albendazole sulfoxide. During the
      whole period of the experiment, the controls remained active and vital throughout
      the 108-h exposure period. The primary site of action of both drugs appears to be
      the mitochondria and myofibrils of the polymyarian musculature. Degenerative
      changes in the secretory portion of the esophagus and somatic musculature were
      clearly observed. These degenerative changes, leading to complete muscular and
      glandular necrosis, were interpreted as the consequence of drug-induced blockade
      of metabolic energy production. Cuticular disruption had also been observed in
      the experimental groups. We observed a dramatic reduction in the number of
      mitochondria and muscle fibers, as well as the formation of large autophagic
      vesicles as result of an irreversible degenerative phenomenon. The passive
      cutaneous elimination of larvae in human infections is probably a consequence of
      parasite immobility, due to the effects of this antihelminthic drug.

PMID- 21744020
TI  - Plasmodium falciparum infection-induced changes in erythrocyte membrane proteins.
AB  - Over the past decade, advances in proteomic and mass spectrometry techniques and
      the sequencing of the Plasmodium falciparum genome have led to an increasing
      number of studies regarding the parasite proteome. However, these studies have
      focused principally on parasite protein expression, neglecting parasite-induced
      variations in the host proteome. Here, we investigated P. falciparum-induced
      modifications of the infected red blood cell (iRBC) membrane proteome, taking
      into account both host and parasite proteome alterations. Furthermore, we also
      determined if some protein changes were associated with genotypically distinct P.
      falciparum strains. Comparison of host membrane proteomes between iRBCs and
      uninfected red blood cells using fluorescence-based proteomic approaches, such as
      2D difference gel electrophoresis revealed that more than 100 protein spots were
      highly up-represented (fold change increase greater than five) following P.
      falciparum infection for both strains (i.e. RP8 and Institut Pasteur Pregnancy
      Associated Malaria). The majority of spots identified by mass spectrometry
      corresponded to Homo sapiens proteins. However, infection-induced changes in host
      proteins did not appear to affect molecules located at the outer surface of the
      plasma membrane. The under-representation of parasite proteins could not be
      attributed to deficient parasite protein expression. Thus, this study describes
      for the first time that considerable host protein modifications were detected
      following P. falciparum infection at the erythrocyte membrane level. Further
      analysis of infection-induced host protein modifications will improve our
      knowledge of malaria pathogenesis.

PMID- 21744021
TI  - Microsatellite analysis of Fasciola spp. in Egypt.
AB  - Recently, the topic of diversity in Fasciola population in Egypt is
      controversial. The present study was performed to study the genetic diversity of
      isolated flukes based on microsatellites markers. Fasciola worms were collected
      from different hosts and geographical locations in Egypt. Control samples of
      Fasciola hepatica from France as well as Fasciola gigantica from Cameroon were
      included in the study. Collected flukes were identified morphologically and
      subjected for analysis using four microsatellite markers. Results of
      microsatellite profile (FM1 and FM2) proved that both species of Fasciola are
      distributed in Egypt irrespective of geographical location and host.
      Nevertheless, the microsatellite profile of some analyzed loci (FM2 and FM3)
      proved that Egyptian flukes showed more alleles compared to the reference ones.
      Differences of microsatellite profile in Egyptian isolates than that of
      corresponding reference samples indicate the remarkable diversity of these
      isolates. The present results highlighted the utility of microsatellite profile
      to discriminate between Fasciola species and to elucidate the diversity within
      the species. To our knowledge, this is the first time to study microsatellite
      polymorphism in Fasciola populations in Egypt.

PMID- 21744022
TI  - Development of a loop-mediated isothermal amplification method for detection of
      Theileria lestoquardi.
AB  - A loop-mediated isothermal amplification (LAMP) assay was developed for the
      diagnosis of Theileria lestoquardi infection. The primers were designed based on
      the clone-5 sequence of T. lestoquardi. The specificity and sensitivity of the
      assay were established. Analysis of the specificity showed that the selected LAMP
      primers amplified the target sequence from T. lestoquardi DNA successfully, while
      no amplification was seen with DNA from Theileria annulata, Theileria ovis,
      Babesia ovis, Anaplasma ovis, or ovine genomic DNA. The specificity of the LAMP
      product was further confirmed by restriction digestion and sequencing. The
      sensitivity of the LAMP assay was analyzed in comparison to PCR resulting in a
      detection limit of 10 fg/MUl of plasmid DNA containing the clone-5 sequence. The
      suitability for utilizing the LAMP assay in the field for the diagnosis of T.
      lestoquardi infection was tested on 100 field samples collected in Sudan and
      compared with results obtained by PCR. The relative specificity and sensitivity
      of the established LAMP assay was determined to be 92.1% and 87.5%, respectively,
      indicating that it may be regarded as an alternative molecular diagnostic tool to
      PCR which could be used for epidemiological surveys on T. lestoquardi infection.

PMID- 21744023
TI  - Effect of zinc and selenium supplementation on serum testosterone and plasma
      lactate in cyclist after an exhaustive exercise bout.
AB  - Zinc and selenium are essential minerals and have roles for more than 300
      metabolic reactions in the body. The purpose of this study was to investigate how
      exhaustive exercise affects testosterone levels and plasma lactate in cyclists
      who were supplemented with oral zinc and selenium for 4 weeks. For this reason,
      32 male road cyclists were selected equally to four groups: PL group, placebo; Zn
      group, zinc supplement (30 mg/day); Se group, selenium supplement (200 MUg/day);
      and Zn-Se group, zinc-selenium supplement. After treatment, free, total
      testosterone, and lactate levels of subjects were determined before and after
      exhaustive exercise. Resting total, free testosterone, and lactate levels did not
      differ significantly between groups, and were increased by exercise (P > 0.05).
      Serum total testosterone levels in Zn group were higher than in Se group after
      exercise (P < 0.05). Serum-free testosterone levels in the Zn group were higher
      than the other groups (P < 0.05).There was an insignificant difference between
      levels of lactate in the four groups after exercise (P > 0.05). The results
      showed that 4-week simultaneous and separately zinc and selenium supplementation
      had no significant effect on resting testosterone and lactate levels of subjects
      who consume a zinc and selenium sufficient diet. It might be possible that the
      effect of zinc supplementation on free testosterone depends on exercise.

PMID- 21744024
TI  - Bat attack! : an unusual cause of keratouveitis.

PMID- 21744025
TI  - An unusual presentation of a simple bone cyst in the scapula.
AB  - A 38-year-old man presented with pain in the left shoulder following a fall. A
      rotator cuff tear was suspected but roentgenograms revealed a lytic, expanded,
      multiseptate lesion of the scapula adjacent to glenoid. This was compatible with
      a giant cell tumor, aneurysmal bone cyst or simple bone cyst. The MRI showed rim
      enhancement and clinched the diagnosis of simple bone cyst. An infraspinous
      approach to scapula was undertaken and open biopsy confirmed the diagnosis of
      simple bone cyst. Definitive treatment in the form of curettage and calcium
      phosphate cementation was carried out. The postoperative period was uneventful.
      Early mobilization was started. Patient remained well on follow-up and has
      returned to work in a physically demanding capacity.

PMID- 21744026
TI  - Treatment of humeral shaft fractures with antegrade intramedullary locking nail.
AB  - Antegrade interlocked humeral nailing for stabilization of humeral fractures was
      introduced many years ago, and studies on this method in the orthopedic
      literature have shown mixed results. The purpose of this investigation was to
      document the clinical outcome and complications associated with the use of an
      antegrade intramedullary nail (T2, Stryker) for the humeral fractures. Between
      2005 and 2008, 52 fractures of the humeral shaft were treated operatively with
      this intramedullary nail in our department. Eight patients were polytraumatized,
      and four patients had an open fracture. The mean age of patients was 51.7 years.
      Forty-eight patients had an adequate duration of clinical follow-up (a mean of 18
      months) for analysis. Complications were recorded, and the time to union was
      measured. Shoulder and elbow functions were assessed using the Constant Score and
      the Morrey Score, respectively. Forty-six fractures healed, with a mean time to
      clinical union of 10.3 weeks. Two patients developed pseudarthroses. There were
      four adverse events: two proximal screws backed out, one superficial infection at
      the insertion point, and one fracture at the distal end of the nail. Ninety-one
      percentage of patients had an excellent or good shoulder function. Five further
      operations were necessary: two for treatment of pseudarthroses, two for removal
      the backed out proximal screws, and one wound debridement for superficial
      infection. Antegrade humeral nailing is a valid therapeutic option for
      stabilization of humeral shaft fractures. By strictly adhering to the operation
      technique, the number and the severity of complications can be reduced. When good
      fracture alignment and stability are obtained, uneventful bone healing with good
      functional results is the rule.

PMID- 21744027
TI  - The verbal portrait: Erik H. Erikson's contribution to psychoanalytic discourse.
AB  - This article makes the case that Erik H. Erikson developed a form of
      psychoanalytic discourse-the verbal portrait-which, although not unprecedented,
      became a focal feature of his work, and the testing ground for the cogency of his
      major contribution to psychoanalysis (the concept of identity). It suggests that
      Erikson was inspired to develop the verbal portrait because he came to
      psychoanalysis from art and was, in fact, a portrait artist. Drawing especially
      on the work of Richard Brilliant, it presents the view that a portrait is a
      portrayal of the subject's identity and goes on to show how Erikson's memorial to
      the cultural anthropologist Ruth Benedict is representative of the verbal
      portrait.

PMID- 21744028
TI  - Haematological and serum biochemical parameters of West African Dwarf goats fed
      dried cassava leaves-based concentrate diets.
AB  - The study was conducted to investigate the effects of feeding different levels of
      dried cassava leaves at 0%, 20%, 40% and 60%, respectively, using guinea grass as
      basal feed, on the haematological and serum biochemical parameters of West
      African Dwarf (WAD) goats. The study lasted for 116 days during which
      haematological and serum biochemical parameters were monitored in 40 male goats
      before and after, using a completely randomized design. At the start of the
      experiment, packed cell volume (PCV) ranged from 21.5% to 25.5% while haemoglobin
      concentration (Hb) and RBC significantly (P < 0.01) ranged from 7.3 to 8.6 g/dl
      and 10.4 to 13.2 * 10(12)/l, respectively. White blood cells reduced
      significantly (P < 0.05)) from 16.4 to 11.7 * 10(9)/l) as dried cassava leaves
      increased in the diets. At the end of the trial, there was a slight increase in
      the values of PCV and Hb in the diets (P > 0.05). Lymphocyte reduced
      significantly (P < 0.05) from 50.0% to 63.5% in the diets. Neutrophils, however,
      increased (P > 0.05) at the 0% to 40% levels and reduced at the 60% level of
      dried cassava leaves inclusion. At the start of the experiment, values for
      glucose significantly (P < 0.05) ranged from 40.1 to 56.0 mg/dl. Total protein
      and albumin values ranged significantly (P < 0.05) from 56.0 to 68.5 g/dl and
      30.6 to 38.4 g/dl, respectively. At the end of the experiment, serum creatinine
      increased significantly (P < 0.05) as the level of dried cassava leaves increased
      from 0% to 60% in the diets. The study revealed that inclusion of dried cassava
      leaves in the diets of West African Dwarf goats had no deleterious effects on the
      haematological and serum biochemical parameters of WAD goats and could therefore
      be included in ruminant diets up to 60%.

PMID- 21744029
TI  - Sequence and phylogenetic analysis of neuraminidase genes of H9N2 avian influenza
      viruses isolated from commercial broiler chicken in Iran (2008 and 2009).
AB  - A total of 512 tissue samples collected from 30 farms located in various states
      of Iran during 2008-2009 as part of a program to monitor avian influenza viruses
      (AIVs) infection in Iran's poultry population. To determine the genetic
      relationship of Iranian viruses, neuraminidase (NA) genes from ten isolates of
      H9N2 viruses isolated from commercial chickens in Iran during 2008-2009 were
      amplified and sequenced. The viruses' neuraminidase gene was >90% similar to
      those of A/Quail/Hong Kong/G1/97 (H9N2) sublineage. The neuraminidase stalk
      regions in these Viruses had no deletion as compared to that of
      chicken/Beijing/1/94 sublineage (Beijing-like viruses) and the two human isolates
      A/HK/1073/99, A/HK/1074/99. Phylogenetic analysis of neuraminidase (NA) gene
      showed that it shares a common ancestor A/Quail/Hong Kong/G1/97 isolate which had
      contributed the internal genes of the H5N1 virus. The results of this study
      indicated that No (Beijing-like) virus and (Korean-like) virus were found in
      chickens in Iran, and the NA genes of H9N2 influenza viruses circulating in Iran
      during the past years were well conserved and the earlier Iranian isolates may be
      considered to represent such a progenitor.

PMID- 21744030
TI  - Mismatch of desired versus perceived social support and associated levels of
      anxiety and depression in newly diagnosed cancer patients.
AB  - PURPOSE: Perceived social support serves as a buffer against stress in cancer
      patients as well as in the healthy. However, not all individuals low in support
      necessarily want more support. We, therefore, tested a match-mismatch model (low
      versus high perceived support relative to low versus high desired support) with
      regard to its association with emotional distress. METHODS: Participants included
      two large samples of n = 576 consecutively recruited, newly diagnosed cancer
      patients and n = 383 healthy controls. The hypothesized interaction effects of
      perceived and desired support and its impact on anxiety and depressive symptoms
      were tested via hierarchical linear regression. RESULTS: Perceived social support
      and desire for support were orthogonal in cancer patients (r = -0.03, p = 0.56).
      In accordance with the match-mismatch model, only those cancer patients with a
      high desire for support but who perceived low support exceeded cut-offs
      suggestive of anxiety and/or depressive disorder, whereas the other patient
      groups did not show clinical symptoms. Results for healthy controls were weaker.
      CONCLUSIONS: The findings support the hypothesized match-mismatch model
      suggesting that lack of social support is only associated with emotional distress
      when patients desire more support than they actually perceive as having.
      Perceived as well as desired social support are, therefore, relevant and non
      overlapping constructs to be included in screening tools for emotional distress
      in order to heighten the utility of screening as a decision aid to guide psycho
      oncological follow-up.

PMID- 21744031
TI  - Psychosocial predictors of children's oral health-related quality of life during
      transition to secondary school.
AB  - PURPOSE: Dental conditions have the potential to impact negatively on children's
      oral health-related quality of life (OHRQoL). However, little attempt has been
      made to investigate how psychosocial variables and significant life events affect
      children's OHRQoL. This research aimed to explore how children's dental status,
      coping, and self-esteem influenced OHRQoL during transition to secondary school.
      METHODS: All patients were undergoing treatment at a UK Dental Hospital. Self
      report questionnaires obtained psychosocial data on self-esteem, coping styles
      and OHRQoL and were completed by children 3 months prior to secondary school
      entry and 3 months following educational transition. Data were extracted from the
      clinical records of the paediatric patients who agreed to participate in the
      research. RESULTS: A total of 92 children aged between 10 and 11 years
      participated at baseline (43% response rate) and 71 of these children
      participated in the follow-up investigation (77% response rate). Multiple lagged
      regression analyses revealed that clinical variables and children's self
      perception of their physical appearance were significant predictors of OHRQoL
      following transition to secondary school. CONCLUSIONS: Children who were
      satisfied with their physical appearance reported fewer impacts on their OHRQoL.
      The mechanisms through which this domain of self-esteem impacts on OHRQoL
      warrants further investigation.

PMID- 21744032
TI  - Measuring health-related quality-of-life for Alzheimer's disease using the
      general public.
AB  - PURPOSE: Little research exists to indicate whether the general public can
      provide proxy health-related quality-of-life (HRQoL) estimates for persons with
      Alzheimer's disease (AD). We investigated (1) whether the general public can
      differentiate between mild, moderate, and severe AD and (2) whether the general
      public's proxy HRQoL estimates are correlated with current health status.
      METHODS: We conducted computer-assisted personal interviews. The computer
      randomly assigned each participant to read a vignette describing mild, moderate,
      or severe AD. Participants answered the EQ-5D-5L and Quality-of-life-Alzheimer's
      Disease (QoL-AD), while imagining living in the health state described in their
      assigned vignette. Participants also answered the EQ-5D-5L based on their health
      state at the time of the interview. RESULTS: We interviewed 100 participants. EQ
      5D-5L utilities were 0.7413 (mild), 0.6159 (moderate), and 0.4456 (severe) (P <
      0.001). Mean QoL-AD scores were 32.5 (mild), 24.0 (moderate), and 21.8 (severe)
      (P < 0.0001 for severe vs. mild, moderate vs. mild; P > 0.05 for severe vs.
      moderate). Participants' EQ-5D-5L utility scores were weakly correlated (r <=
      0.28) across both administrations of the instrument. CONCLUSIONS: The general
      public can differentiate between the three stages of AD, and their HRQoL
      estimates for AD are weakly correlated with their current health status.

PMID- 21744033
TI  - Assessment of the psychological burden associated with pruritus in hemodialysis
      patients using the kidney disease quality of life short form.
AB  - PURPOSE: To assess whether depression symptoms, poor sleep and dry skin bother
      explain association between pruritus and the burden of kidney disease in
      maintenance hemodialysis (MHD) patients. METHODS: Cross-sectional study of 980
      patients from a prospective study in dialysis units of Salvador, Brazil
      (PROHEMO). The Kidney Disease Quality of Life Short Form was used to determine
      scores of kidney disease burden (KDB) and sleep with higher scores indicating
      lower perceived burden and better sleep quality, respectively. The Center for
      Epidemiological Studies Depression Scale was used for depression symptoms.
      RESULTS: Prevalence of severe pruritus (very much or extreme) was 19.4%.
      Significantly (P < 0.001) lower mean KDB score by 11.44 points was observed for
      patients with severe pruritus (34.18 +/- 27.51) than for those with no pruritus
      (45.62 +/- 30.73). Severe pruritus was associated with poorer sleep quality,
      higher odds of dry skin bother and higher depression symptoms score. Association
      of pruritus with KDB score was virtually eliminated after adjustment for sleep,
      dry skin bother and depression symptoms. CONCLUSIONS: This study shows strong
      associations of severe pruritus with higher depression symptoms, poorer sleep and
      dry skin bother among MHD patients. The results support special attention to MHD
      patients with pruritus who often face high psychological burden.

PMID- 21744034
TI  - Nucleic acid-mediated cleavage of M1 gene of influenza A virus is significantly
      augmented by antisense molecules targeted to hybridize close to the cleavage
      site.
AB  - Influenza A virus genome segment 7 encodes protein M1, which is the matrix
      protein playing crucial role in the virus life cycle. Any antiviral strategy that
      aims at reducing, in particular, the expression of this genome segment should, in
      principle, reduce the infectivity of the virus. We developed a specific antiviral
      approach at the molecular level and designed several novel 10-23 DNAzymes (Dz)
      and hammerhead ribozymes (Rz), specifically targeted to cleave at the conserved
      domains of the influenza virus M1 RNA. We sought to use antisense molecules with
      the hope that it will facilitate the ribozyme-mediated cleavage. We observed that
      the Mg(2+)-dependent sequence-specific cleavage of M1 RNA was achieved by both
      the Dz and Rz in a dose-dependent manner. This combination of catalytic Dz and Rz
      with antisense molecules, in principle, resulted in more effective gene
      suppression, inhibited the whole virus replication in host cell, and thus could
      be exploited for therapeutic purposes.

PMID- 21744035
TI  - A modified protocol for RNA extraction from different peach tissues suitable for
      gene isolation and real-time PCR analysis.
AB  - RNA extraction is the first step in the study of gene isolation and expression.
      However, it is difficult to extract high quantity and quality RNA from tissues
      containing large quantities of polysaccharides and polyphenols. Peach (Prunus
      persica), in addition to containing high levels of polysaccharides and
      polyphenols, is a challenging starting material for RNA isolation using a single
      method because of different amounts of those substances in diverse tissues. Based
      on three reported methods, we developed a modified RNA isolation protocol to
      solve this problem, leading to high quality and quantity of total RNA from peach
      mesocarp tissues of fruits which were sampled from all developmental stages and
      different storage periods, as well as from other tissues including flowers,
      leaves, stems, and roots. With our modified method, 28-650 MUg of total RNA was
      routinely obtained from per gram of fresh material, gave at least a 1.16-fold
      improvement by compared with those isolated by other seven methods. The RNA
      extracts were successfully used in downstream applications such as RT-PCR, RACE,
      and real-time PCR.

PMID- 21744036
TI  - The laboratory diagnosis of Bordetella pertussis infection: a comparison of semi
      nested PCR and real-time PCR with culture.

PMID- 21744037
TI  - Amphotericin B and voriconazole susceptibility profiles for the Fusarium solani
      species complex: comparison between the E-test and CLSI M38-A2 microdilution
      methodology.

PMID- 21744038
TI  - Molecular analysis of population structure and antibiotic resistance of
      Klebsiella isolates from a three-year surveillance program in Florence hospitals,
      Italy.
AB  - We report the results of a three-year surveillance program of Klebsiella spp. in
      six hospitals in Florence (Italy). A total of 172 Klebsiella isolates were
      identified and typed by AFLP: 122 were K. pneumoniae and 50 were K. oxytoca. Most
      K. pneumoniae (80%) and K. oxytoca (93%) showed unrelated AFLP profiles. Beside
      this heterogeneous population structure, we found five small epidemic clonal
      groups of K. pneumoniae. Four of these groups were involved in outbreak events,
      three of which occurred in neonatal ICUs. The fifth clonal group spread in three
      different wards of two hospitals. Only one non-epidemic clonal group of K.
      oxytoca was detected. The frequencies of isolates with multiple antibiotic
      resistances increased with time; at the end of the study period, most K.
      pneumoniae were resistant to all the antibiotics tested. A PCR analysis of seven
      ertapenem resistant isolates was unable to detect any of the major genes known to
      underlie carbapenem resistance in K. pneumoniae.

PMID- 21744039
TI  - Glycopeptide resistance in coagulase-negative staphylococci isolated in blood
      cultures from patients with hematological malignancies during three decades.
AB  - The aim of this study was to determine if there was a long-term increase in
      glycopeptide minimum inhibitory concentration (MIC) values, MIC creep, among
      bloodstream isolates of Staphylococcus epidermidis and S. haemolyticus isolated
      from patients with hematological malignancies. We conducted a retrospective
      single-center study where all positive blood cultures of S. epidermidis (n = 387)
      and S. haemolyticus (n = 19) isolated from patients with hematological
      malignancies during three decades, 1980 to 2009, were re-evaluated for the
      presence of reduced susceptibility to vancomycin and teicoplanin. Three different
      methods for the detection of reduced susceptibility to glycopeptides were used;
      standard Etest, macromethod Etest, and glycopeptide resistance detection (GRD)
      Etest. The median MIC value for vancomycin was 2 mg/L. MIC values for vancomycin
      and teicoplanin did not show any statistically significant increase during the
      study period. The presence of heterogeneously glycopeptide-intermediate
      staphylococci (hGIS) was analyzed among 405 coagulase-negative staphylococci
      (CoNS) isolates. hGIS were found in 31-45% of the CoNS isolates by the
      macromethod Etest and in 53-67% by the GRD Etest during the three decades. In
      conclusion, we did not observe any long-term glycopeptide MIC creep determined by
      the standard Etest, although a high and increasing proportion of heterogeneous
      vancomycin resistance was observed.

PMID- 21744040
TI  - Changes in serum levels of biochemical markers of bone turnover during 10 years
      among Japanese men and women: associated factors and birth-cohort effect. The
      Taiji Study.
AB  - We aimed to clarify changes in biochemical markers of bone turnover (BTMs) over
      10 years, associations with changes in bone mineral density (BMD), and birth
      cohort effects in a Japanese community. We randomly selected 400 individuals
      (age, 40-79 years; 50 of each gender and age stratum) from a list of registered
      residents in 1993. We measured BMD of the spine and hip, and serum concentrations
      of total osteocalcin (OC), beta-C-terminal cross-linking telopeptide of type I
      collagen (beta-CTX), and N-terminal cross-linking telopeptide of type I collagen
      (NTX), in 1993 and 2003. Of the 400 subjects, 322 (153 men, 169 women) completed
      the 10-year follow-up. Mean change rates (standard deviation) for serum total OC,
      beta-CTX, and NTX over 10 years were -1.00 (3.74)%/year, 5.10 (22.48)%/year, and
      0.40 (3.41)%/year, respectively, in men, and 0.02 (5.32)%/year, 5.53
      (14.54)%/year, and 0.62 (3.26)%/year, respectively, in women. Change rates of
      BTMs were higher for women in their forties than for women in their fifties to
      seventies (P < 0.05), and higher in the menstrual transition group than in pre-
      and postmenopausal groups (P < 0.001). Changes in levels of BTMs over 10 years in
      women were significantly associated with change rates of BMDs at L2-L4 and total
      hip after adjusting for potential confounders. A significant birth-cohort effect
      was observed among women in their fifties. We concluded that change rates of BTMs
      during the 10 years were influenced by menstrual transition, age, and sex and
      associated with bone loss at L2-L4 and total hip.

PMID- 21744041
TI  - Renal excretion of apricitabine in rats: ex vivo and in vivo studies.
AB  - Apricitabine (ATC) is a novel nucleoside reverse transcriptase inhibitor
      undergoing phase 2/3 clinical development for the treatment of HIV infection. In
      this investigation, the renal handling of ATC was evaluated in the isolated
      perfused rat kidney (IPK) model with follow-up in vivo studies. IPK experiments
      were performed to characterize the renal excretion of ATC, to probe mechanisms of
      ATC excretion using known inhibitors of organic cation (cimetidine) and organic
      anion (probenecid) transport systems, and to screen for potential drug-drug
      interactions between ATC and clinically relevant medications (dapsone, metformin,
      pentamidine, stavudine, tenofovir and ritonavir). ATC demonstrated net tubular
      secretion in the IPK with a baseline excretion ratio (XR) of 2.1 +/- 0.56. ATC XR
      decreased 3.6-fold in the presence of cimetidine and 2-fold in the presence of
      probenecid. Among the clinically relevant medications, metformin produced the
      greatest inhibitory effect on ATC excretion. In vivo studies were conducted in
      rats to evaluate ATC disposition upon co-administration with compounds that
      showed a significant effect on ATC clearance in the IPK model. Co-administration
      of cimetidine and trimethoprim significantly reduced ATC renal clearance, but
      resulted in only a moderate increase in plasma exposure. Metformin had no
      apparent effect on ATC clearance in rats. These findings indicate that the IPK
      model is more sensitive to secretory inhibition as compared to in vivo. The
      medications screened showed minimal effects on ATC renal excretion in the IPK,
      and should thus be excluded as potential in vivo interactants. Overall, this
      study generated important information on renal handling of ATC to support its
      development and commercialization.

PMID- 21744042
TI  - Basal cell carcinoma arising in association with a maxillary keratocyst in a
      patient with Gorlin-Goltz syndrome. Report of a case.
AB  - INTRODUCTION: Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma
      syndrome, is an autosomal dominant inherited disorder which is characterized by
      the presence of multiple basal cell carcinomas, maxillary keratocysts, and
      musculoskeletal anomalies. CASE REPORT: We present a case of a patient suffering
      from Gorlin-Goltz syndrome who developed an intraosseous basal cell carcinoma
      associated with a recurrent maxillary keratocyst. To our knowledge, this is the
      first case of malignant transformation of a keratocyst into a basal cell
      carcinoma described in the literature. CONCLUSION: This case highlights the
      importance of careful histologic examination of keratocysts excised in patients
      suffering from Gorlin-Goltz syndrome.

PMID- 21744043
TI  - Antifungal susceptibility and virulence attributes of bloodstream isolates of
      Candida from Hong Kong and Finland.
AB  - Candida bloodstream infection has dramatically increased in the last decade due
      to the growing number of immunocompromised populations worldwide. In this study,
      we evaluated the antifungal susceptibility profiles and virulence attributes of
      Candida bloodstream isolates (CBIs) derived from Hong Kong and Finland,
      information which are vital for devising empirical clinical strategies.
      Susceptibility testing of a wide range of antifungals including fluconazole,
      itraconazole, voriconazole, ketoconazole, 5-fluorocytosine, amphotericin B and
      caspofungin was performed. Haemolytic activity and secretion of proteinase of
      CBIs were also examined. All CBIs derived from Hong Kong were susceptible to all
      the antifungals tested whilst some CBIs from Finland were resistant to azoles and
      caspofungin. C. albicans, C. glabrata and C. tropicalis showed higher haemolytic
      activity whereas C. parapsilosis and C. guilliermondii were non-haemolytic in
      general. Proteinase activity of the Finland C. albicans isolates was
      significantly higher than the Hong Kong isolates. Our data provide a glimpse of
      the possible evolutionary changes in pathogenic potential of Candida that may be
      occurring in different regions of the world. Therefore, continuous surveillance
      and availability of local data should be taken into consideration when treating
      candidemia patients.

PMID- 21744044
TI  - Isolation of Penicillium marneffei from soil and wild rodents in Guangdong, SE
      China.
AB  - Infection by Penicillium marneffei is an important emerging public health
      problem, especially among travelers and inhabitants in SE China and SE Asia
      infected with human immunodeficiency virus (HIV). In recent years, the number of
      patients with penicilliosis marneffei (PM) has increased rapidly in Guangdong
      province, SE China. However, the natural habitat and transmission mode of the
      etiologic agent remains unclear. In this study, wild rats (Microtus, focus Rattus
      and Rhizomys pruinosus) and soil samples were collected from rat burrows,
      populated and rural areas from November 2007 to December 2008 for fungus
      cultures. All isolates, suspected of being P. marneffei, were identified by gross
      and microscopic morphology and ITS analysis. Sixteen of 23 (about 70%) bamboo
      rats were P. marneffei positive, whereas none was recovered from hamsters, loirs
      or soil. This suggests that as of today the bamboo rat is the exclusive natural
      reservoir for P. marneffei. Definite evidence that rodents are a part of the
      infectious cycle is still lacking.

PMID- 21744045
TI  - Subclinical dissemination of coccidioidomycosis in a liver transplant recipient.
AB  - Coccidioidomycosis is common in the southwestern United States, northern Mexico,
      and areas of South America. Coccidioides immitis and Coccidioides posadasii form
      arthroconidia that, if inhaled, can cause respiratory infection. Rarely, the
      organism disseminates throughout the body, causing disease in bones, lymph nodes,
      skin, joints, and brain in most severe cases. Certain populations are at higher
      risk for dissemination, including persons with compromised cellular immunity.
      This group includes patients with human immunodeficiency virus, patients
      undergoing immunosuppression for rheumatologic disorders, and patients receiving
      antirejection therapy after organ transplant. For patients undergoing a solid
      organ transplant in endemic areas, screening for past or present coccidioidal
      disease is completed pretransplantation. Those with known disease are given
      triazole therapy to prevent reactivation of disease posttransplantation. Usually,
      transplantation is postponed if the disease is active. We present a patient with
      known, active coccidioidomycosis who underwent successful liver transplant and
      later had subclinical posttransplantation peritoneal dissemination.

PMID- 21744047
TI  - Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNgamma
      induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2
      cells.
AB  - We have previously demonstrated that the steroid receptor antagonist mifepristone
      (RU486) causes growth inhibition of Chlamydophila pneumoniae by binding to and
      subsequently destroying the bacteria during their normal developmental cycle in
      epithelial HEp-2 cells. In the present study, we assessed the efficacy of
      treatment with RU486 against persistent C. pneumoniae infection in interferon
      (IFN)gamma-treated HEp-2 cells. Assessment of bacterial growth modification, the
      number of infectious progenies, the formation of inclusions, and the expressions
      of the C. pneumoniae genes 16S rRNA and hsp60 were investigated in cells with or
      without IFNgamma stimulation in the presence of RU486, using an inclusion-forming
      unit (IFU) assay, fluorescence microscopic analysis, and reverse transcription
      polymerase chain reaction (RT-PCR), respectively. Our results indicated that
      RU486 treatment produced growth inhibition and an absence of C. pneumoniae gene
      expression in normal HEp-2 cells and that this treatment failed to inhibit C.
      pneumoniae growth in HEp-2 cells stimulated with IFNgamma. These results indicate
      that treatment with RU486 had a limited effect on C. pneumoniae growth only
      during the active developmental stage of the bacteria, suggesting that the
      bacterial target molecule of RU486 is not expressed sufficiently during
      persistent infection in which there is an aberrant developmental cycle. Thus, our
      findings provide valuable insight into the complicated chlamydial biological
      processes involved in the recurrent cycling between normal and persistent
      infections.

PMID- 21744048
TI  - Label retaining cells and cutaneous stem cells.
AB  - This is a comprehensive review on label retaining cells (LRC) in epidermal
      development and homeostasis. The precise in vivo identification and location of
      epidermal stem cells is a crucial issue in cutaneous biology. We discuss here the
      following problems: (1) Identification and location of LRC in the interfollicular
      epithelium and hair follicle; (2) The proliferative potential of LRC and their
      role in cutaneous homeostasis (3); LRC phenomenon and the Immortal Strand
      Hypothesis, which suggests an alternative mechanism for retention of genetic
      information; (4) Significance of LRC studies for development of stem cell
      concept. Now, it seems evident that LRC are a frequent feature of stem cell
      niches and revealing highly dormant LRC may be used for identification of stem
      cell niches in different tissues. LRC were used for screening specific markers of
      epidermal stem cells. Within a given tissue stem cells have different
      proliferative characteristics. There are more frequently cycling stem cells which
      function primarily in homeostasis, while LRC form a reserve of dormant, may be
      ultimate, stem cells, which are set aside for regeneration of injury or
      unforeseen need. The authors suggest that LRC dormancy described in Mammalia has
      much in common with developmental quiescence found in some other animals. For
      example in C. elegans reproductive system, vulval precursor cells have
      developmentally programmed cell-cycle arrest in the first larval stage, and then
      undergo an extended period of quiescence before resuming proliferation. Another
      example of developmental quiescence is the diapause, a widespread phenomenon
      exhibited by animals ranging from nematodes to mammals, often occurring at
      genetically predetermined life history stage.

PMID- 21744049
TI  - Human fallopian tube mesenchymal stromal cells enhance bone regeneration in a
      xenotransplanted model.
AB  - We have recently reported that human fallopian tubes, which are discarded during
      surgical procedures of women submitted to sterilization or hysterectomies, are a
      rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has
      been previously shown that human mesenchymal stromal cells may be useful in
      enhancing the speed of bone regeneration. This prompted us to investigate whether
      htMSCs might be useful for the treatment of osteoporosis or other bone diseases,
      since they present a pronounced capacity for osteogenic differentiation in vitro.
      Based on this prior knowledge, our aim was to evaluate, in vivo, the osteogenic
      capacity of htMSCs to regenerate bone through an already described
      xenotransplantation model: nonimmunosuppressed (NIS) rats with cranial defects.
      htMSCs were obtained from five 30-50 years old healthy women and characterized by
      flow cytometry and for their multipotenciality in vitro capacity (osteogenic,
      chondrogenic and adipogenic differentiations). Two symmetric full-thickness
      cranial defects on each parietal region of seven NIS rats were performed. The
      left side (LS) of six animals was covered with CellCeram (Scaffdex)-a
      bioabsorbable ceramic composite scaffold that contains 60% hydroxyapatite and 40%
      beta-tricalciumphosphate-only, and the right side (RS) with the CellCeram and
      htMSCs (10(6) cells/scaffold). The animals were euthanized at 30, 60 and 90 days
      postoperatively and cranial tissue samples were taken for histological analysis.
      After 90 days we observed neobone formation in both sides. However, in animals
      euthanized 30 and 60 days after the procedure, a mature bone was observed only on
      the side with htMSCs. PCR and immunofluorescence analysis confirmed the presence
      of human DNA and thus that human cells were not rejected, which further supports
      the imunomodulatory property of htMSCs. In conclusion, htMSCs can be used
      successfully to enhance bone regeneration in vivo, opening a new field for future
      treatments of osteoporosis and bone reconstruction.

PMID- 21744050
TI  - Bio-socio-demographic factors associated with post-traumatic stress disorder in a
      sample of postpartum Brazilian women.
AB  - Post-traumatic stress disorder (PTSD) is common among women. In the postpartum
      period, the prevalence is between 1% and 6%. The present study investigated PTSD
      in a sample of 400 Brazilian women between 2 and 26 weeks postpartum using the
      Mini-International Neuropsychiatric Interview and found a frequency of 5.3%. The
      factors associated with the occurrence of PTSD were low purchasing power, a
      history of psychiatric disorders, clinical disease, and the infant having
      experienced some complication.

PMID- 21744051
TI  - The kynurenine system and immunoregulation.
AB  - There is developing interest in the role of the kynurenines in the immune
      function. A considerable amount of evidence has accumulated as concerns
      interactions between the kynurenine pathway, cytokines and the nervous system.
      Indoleamine 2,3-dioxygenase (IDO) occupies a key position connecting the immune
      system and the kynurenine pathway. There are evidences of the immunosuppressive
      effect of IDO. Following the interferon (IFN)-mediated activation of antigen
      presenting cells, the induction of IDO and the kynurenine system exerts a counter
      regulating effect, maintaining the homeostasis. Inhibition of T cell functions,
      activation of the regulatory T cells, and the inhibition of Natural Killer cells
      are among the important factors in the immunosuppressive effects of IDO and
      kynurenines. There is a close connection between cytokines (IFN-alpha, IFN-gamma,
      TNF-alpha, TGF-beta, IL-4 and IL-23) and the kynurenine system, and an imbalance
      in the TH1/TH2 cytokine profile may possibly lead to neurologic or psychiatric
      disorders. As the tryptophan metabolic pathway is activated by pro-inflammatory
      stimuli, the anti-inflammatory effect of kynurenic acid provides a further
      feedback mechanism in modulating the immune responses.

PMID- 21744055
TI  - The impact of dialysis solution biocompatibility on ultrafiltration and on free
      water transport in rats.
AB  - This study compares different peritoneal dialysis fluids (PDF) in rats over a
      short contact time. For greater accuracy, net ultrafiltration (UF) and peritoneal
      transport indices, mass transfer area coefficient (MTAC) were scaled for the in
      vivo peritoneal surface area recruited (ivPSA) measured by microcomputerized
      tomography. Wistar rats underwent nephrectomy (5/6ths), were randomized into two
      groups and given 1.5% glucose PDF, either conventional acidic lactate (n = 14) or
      pH neutral bicarbonate (BicaVera) (n = 13); MTAC and UF were measured using a 90
      min peritoneal equilibrium test (PET), fill volume (IPV) of 10 ml/100 g; small
      pore fluid transport was determined from sodium balance and used to calculate
      free water transport (FWT). Each ivPSA value was significantly correlated with
      the actual IPV, which varied from one rat to another. At 90 min of contact, there
      was no difference in recruited ivPSA in relation to PDFs. There was a difference
      (p < 0.01) in net UF/ivPSA 0.45 vs. 1.41 cm(2)/ml for bicarbonate versus lactate,
      as there was in the proportion of FWT with bicarbonate (42 +/- 5% of net UF)
      compared to lactate (29 +/- 4% of net UF). Net UF for individual values of ivPSA
      differs between conventional PDF and more biocompatible solutions, such as
      bicarbonate PDF. This observed change in UF cannot be fully explained by
      differences in glucose transport. The changes in FWT may be explained by the
      impact of the PDF biocompatibility on aquaporin function.

PMID- 21744056
TI  - Glucocorticoid-induced hypertension.
AB  - Glucocorticoid-induced hypertension is a common clinical problem that is poorly
      understood, thus rendering treatment strategies sub-optimal. This form of
      hypertension has been commonly thought to be mediated by excess sodium and water
      reabsorption by the renal mineralocorticoid receptor. However, experimental and
      clinical data in both humans and animal models suggest important roles for the
      glucocorticoid receptor as well, in both the pathogenesis and maintenance of this
      hypertension. The glucocorticoid receptor is widely expressed in a number of
      organ systems relevant to blood pressure regulation, including the kidney, the
      brain and the vasculature. In vitro studies in isolated kidney tissues as well as
      in vascular smooth muscle and vascular endothelial cells have attempted to
      elucidate the molecular physiology of glucocorticoid-induced hypertension, but
      have generally been limited by the inability to study signaling pathways in an
      intact organism. More recently, the power of mouse genetics has been employed to
      examine the tissue-specific contributions of vascular and extra-vascular tissues
      to this form of hypertension. Here we review recent developments in our
      understanding of the pathogenesis of glucocorticoid-induced hypertension.

PMID- 21744057
TI  - Treatment of acute lymphoblastic leukemia in adolescents and young adults.
AB  - Treatment approaches for adolescents and young adults with acute lymphoblastic
      leukemia (ALL) have evolved considerably in the past 5-7 years. One of the major
      changes has been the widespread adoption of pediatric-based protocols, which
      appears to have significantly improved survival and probably renders allogeneic
      hematopoietic stem cell transplantation (HSCT) unnecessary in most standard-risk
      patients. However, high-risk patients, such as those with BCR-ABL or MLL
      rearrangements or high white count presentations, should still be referred for
      HSCT in CR-1. Minimal residual disease positivity has also been identified as a
      high-risk feature. Patients with BCR-ABL-positive ALL should receive combined
      therapy with a tyrosine kinase inhibitor and chemotherapy prior to HSCT. The
      adoption of pediatric-based regimens has been associated with significant
      additional toxicities, including venous thromboembolism, osteonecrosis, other
      steroid-related changes, and neuropathy, which can potentially have a major
      adverse impact on the quality of life of these young ALL patients.

PMID- 21744058
TI  - Affective functioning among early adolescents at high and low familial risk for
      depression and their mothers: a focus on individual and transactional processes
      across contexts.
AB  - This study aimed to characterize affective functioning in families of youth at
      high familial risk for depression, with particular attention to features of
      affective functioning that appear to be critical to adaptive functioning but have
      been underrepresented in prior research including: positive and negative affect
      across multiple contexts, individual and transactional processes, and affective
      flexibility. Interactions among early adolescents (ages 9-14) and their mothers
      were coded for affective behaviors across both positive and negative contexts.
      Primary analyses compared never-depressed youth at high (n = 44) and low (n = 57)
      familial risk for depression. The high risk group showed a relatively consistent
      pattern for low positive affect across negative and positive contexts at both the
      individual and transactional level. In contrast to prior studies focusing on
      negative contexts that did not support disruptions in negative affect among high
      risk youth, the data from this study suggest variability by context (i.e.
      increased negativity in a positive, but not negative, context), and individual
      vs. transactional processes (e.g., negative escalation). Findings are discussed
      in concert with attention to affect flexibility, contextual and transactional
      factors.

PMID- 21744059
TI  - Childhood social withdrawal, interpersonal impairment, and young adult
      depression: a mediational model.
AB  - Building on interpersonal theories of depression, the current study sought to
      explore whether early childhood social withdrawal serves as a risk factor for
      depressive symptoms and diagnoses in young adulthood. The researchers
      hypothesized that social impairment at age 15 would mediate the association
      between social withdrawal at age 5 and depression by age 20. This mediational
      model was tested in a community sample of 702 Australian youth followed from
      mother's pregnancy to youth age 20. Structural equation modeling analyses found
      support for a model in which childhood social withdrawal predicted adolescent
      social impairment, which, in turn, predicted depression in young adulthood.
      Additionally, gender was found to moderate the relationship between adolescent
      social impairment and depression in early adulthood, with females exhibiting a
      stronger association between social functioning and depression at the symptom and
      diagnostic level. This study illuminates one potential pathway from early
      developing social difficulties to later depressive symptoms and disorders.

PMID- 21744060
TI  - Inadequate cancer pain management in Italian clinical trials.
AB  - Pain treatment in Italy is far from being optimal. In order to improve this
      situation, the reporting of a complete assessment of pain in the clinical record
      became compulsory by law. Pain-related cancer protocols (143) were selected from
      the National Monitoring Centre of Clinical Trials Database and reviewed. Our data
      indicate that pain management is not being reported as it should be: treatment
      has been taken into account in only 36.4% of the protocols, and assessment in
      37.1%. Furthermore, breakthrough cancer pain has never been reported. The main
      aim of cancer therapy is obviously control the disease, however Ethics Committees
      should pay close attention to pain therapy when evaluating clinical protocols. 

PMID- 21744061
TI  - Effects of a structured physical activity intervention on measures of physical
      performance in frail elderly patients after cardiac rehabilitation: a pilot study
      with 1-year follow-up.
AB  - The objective of this prospective randomized controlled study was to compare the
      long-term effects of a structured physical activity intervention with those of
      aerobic exercises alone, in a cohort of elderly patients who had undergone
      elective cardiac surgery, and who were classified as frail at the end of
      rehabilitation based on their Short Physical Performance Battery (SPPB) score. At
      the end of rehabilitation, 140 frail elderly patients were randomly allocated
      either to the intervention group (IG) or to the control group (CG). CG
      participants received the usual aerobic exercise prescription, while IG
      participants were also taught additional exercises for strength, flexibility,
      balance and coordination. The improvement in SPPB score after 1 year was the
      outcome of the study. IG showed a significant improvement in SPPB score (9.0 +/-
      1.1 vs. 7.7 +/- 1.4, p < 0.001), while no significant change was found in CG (7.7
      +/- 1.6 vs. 7.6 +/- 1.5, p = 0.252). IG also showed a significantly higher
      proportion of participants who improved their SPPB score of at least 1 point (70
      vs. 37%, p < 0.001). In conclusions, our structured physical activity
      intervention significantly improves the SPPB score in frail elderly patients who
      have undergone elective cardiac surgery. An intervention that improves the SPPB
      score might delay the occurrence of mobility disability. 

PMID- 21744062
TI  - Pharmaco-economics and decision making in health care. The case of "Extended
      prophylaxis of venous thromboembolism with fondaparinux in patients undergoing
      major orthopaedic surgery in Italy: a cost-effectiveness analysis".

PMID- 21744063
TI  - Description of an AGPAT2 pathologic allelic variant in a 54-year-old Caucasian
      woman with Berardinelli-Seip syndrome.
AB  - A 54-year-old Italian female patient was admitted to our Department with the
      diagnosis of type 2 diabetes poorly controlled with insulin therapy. The patient
      was born by consanguineous parents (first degree cousins); she had acromegaloid
      features, diffuse lipoatrophy and muscular pseudo-hypertrophy since childhood. To
      confirm the clinical hypothesis of congenital generalized lipodystrophy (CGL) or
      Berardinelli-Seip syndrome, the sequences of AGPAT2 (encoding for 1-acyl-sn
      glycerol-3-phosphate acyltransferase beta) and BSCL2 (encoding for seipin)
      candidate genes were analyzed. DNA analysis showed the presence of a homozygous
      mutation in exon 3 of the AGPAT2 gene (P112L). This is the first description of a
      Caucasian subject with CGL who carries the pathologic allelic variant P112L of
      the AGPAT2 gene.

PMID- 21744064
TI  - Hes-1 regulates the excitatory fate of neural progenitors through modulation of
      Tlx3 (HOX11L2) expression.
AB  - Tlx3 (HOX11L2) is regarded as one of the selector genes in excitatory versus
      inhibitory fate specification of neurons in distinct regions of the nervous
      system. Expression of Tlx3 in a post-mitotic immature neuron favors a
      glutamatergic over GABAergic fate. The factors that regulate Tlx3  have immense
      importance in the fate specification of glutamatergic neurons. Here, we have
      shown that Notch target gene, Hes-1, negatively regulates Tlx3 expression,
      resulting in decreased generation of glutamatergic neurons. Down-regulation of
      Hes-1 removed the inhibition on Tlx3 promoter, thus promoting glutamatergic
      differentiation. Promoter-protein interaction studies with truncated/mutated Hes
      1 protein suggested that the co-repressor recruitment mediated through WRPW
      domain of Hes-1 has contributed to the repressive effect. Our results clearly
      demonstrate a new and unique role for canonical Notch signaling through Hes-1, in
      neurotransmitter/subtype fate specification of neurons in addition to its known
      functional role in proliferation/maintenance of neural progenitors.

PMID- 21744065
TI  - Cytoglobin: biochemical, functional and clinical perspective of the newest member
      of the globin family.
AB  - Since the discovery of cytoglobin (Cygb) a decade ago, growing amounts of data
      have been gathered to characterise Cygb biochemistry, functioning and implication
      in human pathologies. Its molecular roles remain under investigation, but nitric
      oxide dioxygenase and lipid peroxidase activities have been demonstrated. Cygb
      expression increases in response to various stress conditions including hypoxia,
      oxidative stress and fibrotic stimulation. When exogenously overexpressed, Cygb
      revealed cytoprotection against these factors. Cygb was shown to be upregulated
      in fibrosis and neurodegenerative disorders and downregulated in multiple cancer
      types. CYGB was also found within the minimal region of a hereditary tylosis with
      oesophageal cancer syndrome, and its expression was reduced in tylotic samples.
      Recently, Cygb has been shown to inhibit cancer cell growth in vitro, thus
      confirming its suggested tumour suppressor role. This article aims to review the
      biochemical and functional aspects of Cygb, its involvement in various
      pathological conditions and potential clinical utility.

PMID- 21744066
TI  - The biology of interleukin-1: emerging concepts in the regulation of the actin
      cytoskeleton and cell junction dynamics.
AB  - Interleukin (IL)-1 is a proinflammatory cytokine with important roles in innate
      immunity, as well as in normal tissue homeostasis. Interestingly, recent studies
      have also shown IL-1 to function in the dynamics of the actin cytoskeleton and
      cell junctions. For example, treatment of different epithelia with IL-1alpha
      often results in the restructuring of the actin network and cell junctions,
      thereby leading to junction disassembly. In this review, we highlight new and
      interesting findings that show IL-1 to be a critical player of restructuring
      events in the seminiferous epithelium of the testis during spermatogenesis.

PMID- 21744069
TI  - Inhibition of Helicobacter pylori adhesion to Kato III cells by intact and low
      molecular weight acharan sulfate.
AB  - We investigated the inhibitory activity of glycosaminoglycans (GAGs) in terms of
      growth, adhesion, and VacA vacuolation of Helicobacter pylori. Intact acharan
      sulfate (AS, MW:114 kDa) potently inhibited H. pylori adhesion to Kato III cells
      with IC(50) value of 1.4 mg/mL, while other GAGs did not show any inhibitory
      activity except for heparin which is a well-known inhibitor of H. pylori
      adhesion. To investigate whether low molecular weight acharan sulfate (LMWAS) can
      inhibit H. pylori adhesion, we performed chemical depolymerization of AS by
      radical reactions to obtain LMWAS. Its physicochemical properties were
      characterized by high-performance size exclusion chromatography (HPSEC), agarose
      gel electrophoresis, disaccharide compositional analysis after digestion with
      heparinase II, and (1)H-NMR spectroscopy. The most potent molecular size of LMWAS
      was 3 kDa with IC(50) value of 32 MUg/mL, which is 44-fold more potent than
      intact AS. These results suggest that AS as well as other GAGs can be chemically
      depolymerized by free radicals and LMWAS compared to intact AS can be applied as
      a pharmaceutical candidate in order to inhibit H. pylori adhesion to Kato III
      cells.

PMID- 21744068
TI  - Biochemistry of the non-mevalonate isoprenoid pathway.
AB  - The non-mevalonate pathway of isoprenoid (terpenoid) biosynthesis is essential in
      many eubacteria including the major human pathogen, Mycobacterium tuberculosis,
      in apicomplexan protozoa including the Plasmodium spp. causing malaria, and in
      the plastids of plants. The metabolic route is absent in humans and is therefore
      qualified as a promising target for new anti-infective drugs and herbicides.
      Biochemical and structural knowledge about all enzymes involved in the pathway
      established the basis for discovery and development of inhibitors by high
      throughput screening of compound libraries and/or structure-based rational
      design.

PMID- 21744067
TI  - Cyclic AMP: a selective modulator of NF-kappaB action.
AB  - It has been known for several decades that cyclic AMP (cAMP), a prototypical
      second messenger, transducing the action of a variety of G-protein-coupled
      receptor ligands, has potent immunosuppressive and anti-inflammatory actions.
      These actions have been attributed in part to the ability of cAMP-induced signals
      to interfere with the function of the proinflammatory transcription factor
      Nuclear Factor-kappaB (NF-kappaB). NF-kappaB plays a crucial role in switching on
      the gene expression of a plethora of inflammatory and immune mediators, and as
      such is one of the master regulators of the immune response and a key target for
      anti-inflammatory drug design. A number of fundamental molecular mechanisms,
      contributing to the overall inhibitory actions of cAMP on NF-kappaB function, are
      well established. Paradoxically, recent reports indicate that cAMP, via its main
      effector, the protein kinase A (PKA), also promotes NF-kappaB activity. Indeed,
      cAMP actions appear to be highly cell type- and context-dependent. Importantly,
      several novel players in the cAMP/NF-kappaB connection, which selectively direct
      cAMP action, have been recently identified. These findings not only open up
      exciting new research avenues but also reveal novel opportunities for the design
      of more selective, NF-kappaB-targeting, anti-inflammatory drugs.

PMID- 21744070
TI  - Poly(I:C) induce bone marrow precursor cells into myeloid-derived suppressor
      cells.
AB  - Dendritic cells (DC) and myeloid-derived suppressor cells (MDSC) are important
      cells involved in immune response. DC can be generated from mouse bone marrow
      (BM) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      and IL-4. Recent studies have revealed that combined treatment of bone marrow
      MDSC with LPS plus IFN-gamma inhibited the DC development but enhanced MDSC
      functions, such as NO release and T cell suppression. In our study, bone marrow
      precursor cells cultures in GM-CSF and IL-4 were treated with poly(I:C) through
      the culture, Gr1(+)CD11b(+) cells with MDSC functions, such as NO release and T
      cell suppression were accumulated in the culture system. Then the similar
      phenomenon was observed in the vesicular stomatitis virus infection in vivo. In
      conclusion, we demonstrated that the bone marrow precursor cells in the presence
      of GM-CSF and IL-4 can differentiate into MDSC, which is dependent on the dynamic
      of interaction with poly(I:C).

PMID- 21744071
TI  - Intracrine action of angiotensin II in the intact ventricle of the failing heart:
      angiotensin II changes cardiac excitability from within.
AB  - The influence of intracellular injection of angiotensin II (Ang II) on electrical
      properties of single right ventricular fibers from the failing heart of
      cardiomyopathic hamsters (TO2) was investigated in the intact ventricle of 8
      month-old animals. Intracellular injection was performed using pressure pulses
      (40-70 psi) for short periods of time (20 ms) while recoding the action potential
      simultaneously from the same fiber. The results indicated that intracellular Ang
      II caused a hyperpolarization of 7.7 mV +/- 4.3 mV (n = 39) (4 animals) (P <
      0.05) followed by a small fall in membrane potential. The action potential
      duration was significantly increased at 50% and at 90% repolarization, and the
      refractoriness was significantly enhanced. The effect of intracellular Ang II on
      action potential duration was related to the inhibition of potassium conductance
      through PKC activation because Bis-1 (360 nM), a selective PKC inhibitor,
      abolished the effect of the peptide. Injections performed in different fibers of
      the same ventricle showed a variable effect of Ang II on action potential
      duration and generated spontaneous rhythmicity. The effect of intracellular Ang
      II on action potential duration and cardiac refractoriness remains for more than
      1 h after interruption of the intracellular injection of the peptide.

PMID- 21744072
TI  - Anatomical landmarks for transnasal endoscopic skull base surgery.
AB  - Resection of midline skull base lesions involve approaches needing extensive
      neurovascular manipulation. Transnasal endoscopic approach (TEA) is minimally
      invasive and ideal for certain selected lesions of the anterior skull base. A
      thorough knowledge of endonasal endoscopic anatomy is essential to be well versed
      with its surgical applications and this is possible only by dedicated cadaveric
      dissections. The goal in this study was to understand endoscopic anatomy of the
      orbital apex, petrous apex and the pterygopalatine fossa. Six cadaveric heads (3
      injected and 3 non injected) and 12 sides, were dissected using a TEA outlining
      systematically, the steps of surgical dissection and the landmarks encountered.
      Dissection done by the "2 nostril, 4 hands" technique, allows better transnasal
      instrumentation with two surgeons working in unison with each other. The main
      surgical landmarks for the orbital apex are the carotid artery protuberance in
      the lateral sphenoid wall, optic nerve canal, lateral optico-carotid recess,
      optic strut and the V2 nerve. Orbital apex includes structures passing through
      the superior and inferior orbital fissure and the optic nerve canal. Vidian nerve
      canal and the V2 are important landmarks for the petrous apex. Identification of
      the sphenopalatine artery, V2 and foramen rotundum are important during
      dissection of the pterygopalatine fossa. In conclusion, the major potential
      advantage of TEA to the skull base is that it provides a direct anatomical route
      to the lesion without traversing any major neurovascular structures, as against
      the open transcranial approaches which involve more neurovascular manipulation
      and brain retraction. Obviously, these approaches require close cooperation and
      collaboration between otorhinolaryngologists and neurosurgeons.

PMID- 21744073
TI  - C-reactive protein promotes diabetic kidney disease in a mouse model of type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: Although C-reactive protein (CRP) has been implicated as a risk
      factor in diabetes, its pathogenic importance in diabetic kidney disease (DKD)
      remains unclear. The present study investigated the potential role of CRP in DKD.
      METHODS: Diabetes was induced by streptozotocin in human CRP transgenic and wild
      type mice for assessment of kidney injury at 24 weeks by real-time PCR,
      immunohistochemistry and western blot analysis. In vitro, the pathogenic effect
      of CRP was investigated using human kidney tubular epithelial cells cultured with
      high glucose and/or CRP. RESULTS: We found that CRP transgenic mice developed
      much more severe diabetic kidney injury than wild-type mice, as indicated by a
      significant increase in urinary albumin excretion and kidney injury molecule-1
      abundance, enhanced infiltration of macrophages and T cells, and upregulation of
      pro-inflammatory cytokines (IL-1beta, TNFalpha) and extracellular matrix
      (collagen I, III and IV). Enhanced renal inflammation and fibrosis in CRP
      transgenic mice was associated with upregulation of CRP receptor, CD32a, and over
      activation of the TGF-beta/SMAD and nuclear factor kappaB signalling pathways. In
      vitro, CRP significantly upregulated pro-inflammatory cytokines (IL-1beta,
      TNFalpha, monocyte chemoattractant protein-1 [MCP-1]) and pro-fibrotic growth
      factors (TGF-beta1, connective tissue growth factor [CTGF]) via CD32a/64. CRP was
      induced by high glucose, which synergistically promoted high glucose-mediated
      renal inflammation and fibrosis. CONCLUSIONS/INTERPRETATION: CRP is not only a
      biomarker, but also a mediator in DKD. Enhanced activation of TGF-beta/SMAD and
      nuclear factor kappaB signalling pathways may be the mechanisms by which CRP
      promotes renal inflammation and fibrosis under diabetic conditions.

PMID- 21744074
TI  - Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural
      killer T cells: lessons from obesity, diabetes and psoriasis.
AB  - AIMS/HYPOTHESIS: The innate immune cells, invariant natural killer T cells (iNKT
      cells), are implicated in the pathogenesis of psoriasis, an inflammatory
      condition associated with obesity and other metabolic diseases, such as diabetes
      and dyslipidaemia. We observed an improvement in psoriasis severity in a patient
      within days of starting treatment with an incretin-mimetic, glucagon-like peptide
      1 (GLP-1) receptor agonist. This was independent of change in glycaemic control.
      We proposed that this unexpected clinical outcome resulted from a direct effect
      of GLP-1 on iNKT cells. METHODS: We measured circulating and psoriatic plaque
      iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and
      after commencing GLP-1 analogue therapy. In addition, we investigated the in
      vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor
      on these cells. RESULTS: The Psoriasis Area and Severity Index improved in both
      patients following 6 weeks of GLP-1 analogue therapy. This was associated with an
      alteration in iNKT cell number, with an increased number in the circulation and a
      decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT
      cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine
      secretion, but not cytolytic degranulation in vitro. CONCLUSIONS/INTERPRETATION:
      The clinical effect observed and the direct interaction between GLP-1 and the
      immune system raise the possibility of therapeutic applications for GLP-1 in
      inflammatory conditions such as psoriasis.

PMID- 21744075
TI  - Exogenous ghrelin improves blood flow distribution in pulmonary hypertension
      assessed using synchrotron radiation microangiography.
AB  - Ghrelin has cardioprotective properties and, recently, has been shown to improve
      endothelial function and reduce endothelin-1 (ET-1)-mediated vasoconstriction in
      peripheral vascular disease. Recently, we reported that ghrelin attenuates
      pulmonary hypertension (PH) caused by chronic hypoxia (CH), which we hypothesized
      in this study may be via suppression of the ET-1 pathway. We also aimed to
      determine whether ghrelin's ability to prevent alterations of the ET-1 pathway
      also prevented adverse changes in pulmonary blood flow distribution associated
      with PH. Sprague-Dawley rats were exposed to CH (10% O(2) for 2 weeks) with daily
      subcutaneous injections of ghrelin (150 MUg/kg) or saline. Utilizing synchrotron
      radiation microangiography, we assessed pulmonary vessel branching structure,
      which is indicative of blood flow distribution, and dynamic changes in vascular
      responsiveness to (1) ET-1 (1 nmol/kg), (2) the ET-1(A) receptor antagonist, BQ
      123 (1 mg/kg), and (3) ACh (3.0 MUg kg-1 min-1). CH impaired blood flow
      distribution throughout the lung. However, this vessel "rarefaction" was
      attenuated in ghrelin-treated CH-rats. Moreover, ghrelin (1) reduced the
      magnitude of endothelial dysfunction, (2) prevented an increase in ET-1-mediated
      vasoconstriction, and (3) reduced pulmonary vascular remodeling and right
      ventricular hypertrophy-all adverse consequences associated with CH. These
      results highlight the beneficial effects of ghrelin for maintaining optimal lung
      perfusion in the face of a hypoxic insult. Further research is now required to
      establish whether ghrelin is also an effective therapy for restoring normal
      pulmonary hemodynamics in patients that already have established PH.

PMID- 21744076
TI  - A new tool for grade II glioma studies: plotting cumulative time with quality of
      life versus time to malignant transformation.

PMID- 21744077
TI  - A functional polymorphism in the pre-miR-146a gene is associated with risk and
      prognosis in adult glioma.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that function as post-transcriptional
      regulators of tumor suppressors and oncogenes. Single nucleotide polymorphisms
      (SNPs) in miRNAs may contribute to carcinogenesis by altering expression of
      miRNAs and their targets. A G>C polymorphism (rs2910164) in the miR-146a
      precursor sequence leads to a functional change associated with the risk for
      numerous malignancies. A role for this SNP in glioma pathogenesis has not yet
      been examined. We investigated whether rs2910164 genotypes influence glioma risk
      and prognosis in a multi-center case-control study comprised of 593 Caucasian
      glioma cases and 614 community-based controls. Unconditional logistic regression
      was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for
      rs2910164 genotypes according to case status. Cox proportional hazards regression
      modeling was used to estimate hazards ratios (HR) and 95% CIs according to
      genotype among glioblastomas, the most lethal glioma subtype. An increased glioma
      risk was observed among rs2910164 minor allele (C) carriers (per allele OR (95%
      CI) = 1.22 (1.01-1.46, p (trend) = 0.039)). The association was stronger among
      older subjects carrying at least one copy of the C allele (OR (95% CI) = 1.38
      (1.04-1.83, P = 0.026). Mortality was increased among minor allele carriers (HR
      (95% CI) = 1.33 (1.03-1.72, P = 0.029)), with the association largely restricted
      to females (HR (95% CI) = 2.02 (1.28-3.17, P = 0.002)). We provide novel data
      suggesting rs2910164 genotype may contribute to glioma susceptibility and
      outcome. Future studies are warranted to replicate these findings and
      characterize mechanisms underlying these associations.

PMID- 21744078
TI  - Gefitinib induces apoptosis in human glioma cells by targeting Bad
      phosphorylation.
AB  - Gefitinib, a selective epidermal growth factor receptor tyrosine kinase
      inhibitor, is under clinical testing and use in cancer patients, including
      glioma. However, the molecular mechanisms involved in gefitinib-mediated
      anticancer effects against glioma remain largely uncharacterized. Gefitinib
      inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also
      induces death of H4 cells with characteristics of the intrinsic apoptotic
      pathway, including Bax mitochondrial translocation, mitochondrial outer membrane
      permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3
      activation. The importance of Bax in mediating gefitinib-induced apoptosis was
      confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker.
      Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased
      its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in
      gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP
      content and protein kinase A (PKA) activity. Adenylyl cyclase activator forskolin
      attenuated, but PKA inhibitor H89 augmented, gefitinib-induced Bad
      dephosphorylation, Bax mitochondrial translocation, caspase-9/caspase-3
      activation, and viability loss. Intriguingly, a nonselective protein phosphatase
      inhibitor okadaic acid alleviated gefitinib-induced alterations, except Bad
      dephosphorylation. In parallel with the higher basal PKA activity, response of
      U87 cells to gefitinib treatment was delayed and relatively resistant compared
      with that of H4 and T98G cells. Inactivation of PKA sensitized H4, T98G, and U87
      cells to gefitinib cytotoxicity, Bad dephosphorylation in serine-112, and caspase
      9/caspase-3 activation. Our findings suggest the involvement of the Bad/Bax
      signaling pathway in gefitinib-induced glioma apoptosis. Furthermore, the
      inactivation of PKA was shown to play a role in triggering the proapoptotic
      function of Bad.

PMID- 21744079
TI  - Phase I study of sunitinib and irinotecan for patients with recurrent malignant
      glioma.
AB  - We determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT)
      of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor,
      sunitinib, when administered with irinotecan among recurrent malignant glioma
      (MG) patients. For each 42-day cycle, sunitinib was administered once a day for
      four consecutive weeks followed by a 2 week rest. Irinotecan was administered
      intravenously every other week. Each agent was alternatively escalated among
      cohorts of 3-6 patients enrolled at each dose level. Patients on CYP3A-inducing
      anti-epileptic drugs were not eligible. Twenty-five patients with recurrent MG
      were enrolled, including 15 (60%) with glioblastoma (GBM) and 10 (40%) with grade
      3 MG. Five patients progressed previously on bevacizumab and two had received
      prior VEGFR tyrosine kinase inhibitor therapy. The MTD was 50 mg of sunitinib
      combined with 75 mg/m(2) of irinotecan. DLT were primarily hematologic and
      included grade 4 neutropenia in 3 patients and one patient with grade 4
      thrombocytopenia. Non-hematologic DLT included grade 3 mucositis (n = 1) and
      grade 3 dehydration (n = 1). Progression-free survival (PFS)-6 was 24% and only
      one patient achieved a radiographic response. The combination of sunitinib and
      irinotecan was associated with moderate toxicity and limited anti-tumor activity.
      Further studies with this regimen using the dosing schedules evaluated in this
      study are not warranted.

PMID- 21744080
TI  - Central nervous system pathology in fatal swine-origin influenza A H1N1 virus
      infection in patients with and without neurological symptoms: an autopsy study of
      15 cases.

PMID- 21744081
TI  - Participation of ventral and dorsal tail muscles in bending movements of rat
      tail.
AB  - The rat controls the form of its tail, from straight to curved, by contraction
      and relaxation of its four tail muscles. The tendons of these muscles insert on
      any of the cranial articular, transverse, and hemal processes of each of 24
      coccygeal vertebrae (Co5-Co28). In this study, we isolated for the four coccygeal
      muscles each muscular fascicle segment inserting on any process of the coccygeal
      vertebrae. We measured the length and weight of all muscular fascicles and
      tendons, and then divided all muscular fascicles into four groups based on their
      insertion: Co5-Co10, Co11-Co16, Co17-Co22, and Co23-Co28. Moreover, we used soft
      X-ray imaging to investigate the geometrical relationship between neighboring
      coccygeal vertebrae. Additionally we carried out serial sectioning at the sacral
      and caudal portions, and traced the course of the tendons of coccygeal muscles
      from their origin to the Co4 level. We discuss which muscles and tendons play
      important roles when coccygeal vertebrae bend along and rotate around the
      longitudinal axis.

PMID- 21744082
TI  - Updated survival analysis in patients with stage IIIB or IV non-small-cell lung
      cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized,
      multicenter, open-label trial.
AB  - PURPOSE: To present an updated survival analysis of an open-label, parallel
      group, phase IIB trial of BLP25 liposome vaccine (L-BLP25) in patients with stage
      IIIB or IV non-small-cell lung cancer (NSCLC). METHODS: Patients were randomized
      to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L
      BLP25 arm received subcutaneous vaccinations of L-BLP25 930 MUg weekly for 8
      weeks, followed by maintenance vaccinations at 6-week intervals. RESULTS: Median
      survival time was 4.2 months longer in patients receiving L-BLP25 plus BSC (n =
      88) than in those receiving BSC alone (n = 83; 17.2 months vs. 13.0 months,
      respectively; hazard ratio [HR] 0.745, 95% confidence interval [CI] 0.533-1.042).
      The 3-year survival rate was 31% in patients receiving L-BLP25 plus BSC and 17%
      in those receiving BSC (P = 0.035). In the stratified subset of patients with
      stage IIIB loco-regional (LR) disease, median survival time was 17.3 months
      longer in patients receiving L-BLP25 plus BSC (n = 35) than in those receiving
      BSC (n = 30; 30.6 months vs. 13.3 months, respectively; HR 0.548, 95% CI 0.301
      0.999). In this subgroup, 3-year survival was 49% in patients receiving L-BLP25
      plus BSC and 27% in those receiving BSC (P = 0.070). CONCLUSIONS: Confirming the
      initial results, further follow-up continues to show that survival time for
      patients with stage IIIB/IV NSCLC was longer with L-BLP25 plus BSC compared with
      BSC alone, with the greatest difference seen in patients with stage IIIB LR
      disease.

PMID- 21744083
TI  - Migration of MDA-MB-231 breast cancer cells depends on the availability of
      exogenous lipids and cholesterol esterification.
AB  - We previously described a lipid-accumulating phenotype of estrogen receptor
      negative (ER(-)) breast cancer cells exemplified by the MDA-MB-231 and MDA-MB-436
      cell lines. These cells had more lipid droplets, a higher uptake of oleic acid
      and LDL, a higher ratio of cholesteryl ester (CE) to triacylglycerol (TAG), and
      higher expression of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) as compared
      to ER(+) MCF-7 breast cancer cells. LDL stimulated proliferation of ER-cells
      only, and proliferation was reduced by inhibition of ACAT. We hypothesized that
      storage of exogenous lipids would confer an energetic advantage. We tested this
      by depriving cells of exogenous lipids and measuring chemotactic migration, an
      energy-intensive behavior. MDA-MB-231 cells were grown for 48 h in medium with
      either 5% FBS or 5% lipoprotein-depleted (LD) FBS. Growth in LD medium resulted
      in visibly reduced lipid droplets and an 85% decrease in cell migration. Addition
      of LDL to the LD medium dose-dependently restored the ability to migrate in an
      ACAT-sensitive manner. LDL receptor (LDLR) mRNA was 12-fold higher in MDA-MB-231
      cells compared to nontumorigenic ER-MCF-10A breast epithelial cells grown in LD
      medium. Addition of LDL to the LD medium reduced LDLR mRNA levels in MCF-10A
      cells only. We asked if ACAT1 activity was associated with the expression of the
      LDLR in MDA-MB-231 cells. LDLR mRNA in MDA-MB-231 cells was substantially reduced
      by inhibition of ACAT, demonstrating that high ACAT1 activity permitted higher
      LDLR expression. This data substantiates the association of lipid accumulation
      with aggressive behavior in an ER-breast cancer cell line.

PMID- 21744084
TI  - Clinical and pathological analysis of 27 patients with combined hepatocellular
      cholangiocarcinoma in an Asian center.
AB  - BACKGROUND: Our purpose was to assess the clinicopathological features and
      surgical outcomes of combined hepatocellular-cholangiocarcinoma (HCC-CC) in an
      Asian center. METHODS: Between 1998 and 2009, 27 patients were diagnosed with
      combined HCC-CC at our hospital. Their medical records were reviewed and
      clinicopathological data retrospectively analyzed. RESULTS: The 27 patients
      included 24 (88.9%) males and 3 (11.1%) females with a mean age of 58.26 +/-
      11.18 years. Cirrhosis was present in 10 patients (37.0%), and 12 patients had
      hepatitis C or hepatitis B virus infection. Serum alpha fetoprotein was >20 ng/ml
      in 7 of the 19 patients in whom it was measured (36.8%). Twenty-five patients
      underwent hepatic resections and 2 received liver transplantations. Five (18.5%)
      patients had separate HCC and CC within the same liver (type I), 21 (77.8%) had
      tumors with mixed components (type II), and 1 patient had a type III tumor
      (3.7%). Of 22 patients with immunohistochemical data, 19 (86.4%) were cytokeratin
      (CK) 7-positive, 20 (90.9%) were CK19-positive, and 4 (18.2%) were CK20-positive.
      Mean follow-up was 25.8 months. The 1- and 2-year survival rates were 72.5 and
      49.4%, respectively. The 1- and 2-year disease-free survival rates were 54.2 and
      41.3%, respectively. Symptoms at the time of diagnosis, and regional lymph node
      metastases, were associated with higher mortality and recurrence. CONCLUSIONS:
      Lymph node metastasis and positive resection margins are important factors
      affecting HCC-CC surgical outcomes.

PMID- 21744085
TI  - TREK: an integrated system architecture for intraoperative cone-beam CT-guided
      surgery.
AB  - PURPOSE: A system architecture has been developed for integration of
      intraoperative 3D imaging [viz., mobile C-arm cone-beam CT (CBCT)] with surgical
      navigation (e.g., trackers, endoscopy, and preoperative image and planning data).
      The goal of this paper is to describe the architecture and its handling of a
      broad variety of data sources in modular tool development for streamlined use of
      CBCT guidance in application-specific surgical scenarios. METHODS: The
      architecture builds on two proven open-source software packages, namely the cisst
      package (Johns Hopkins University, Baltimore, MD) and 3D Slicer (Brigham and
      Women's Hospital, Boston, MA), and combines data sources common to image-guided
      procedures with intraoperative 3D imaging. Integration at the software component
      level is achieved through language bindings to a scripting language (Python) and
      an object-oriented approach to abstract and simplify the use of devices with
      varying characteristics. The platform aims to minimize offline data processing
      and to expose quantitative tools that analyze and communicate factors of
      geometric precision online. Modular tools are defined to accomplish specific
      surgical tasks, demonstrated in three clinical scenarios (temporal bone, skull
      base, and spine surgery) that involve a progressively increased level of
      complexity in toolset requirements. RESULTS: The resulting architecture (referred
      to as "TREK") hosts a collection of modules developed according to application
      specific surgical tasks, emphasizing streamlined integration with intraoperative
      CBCT. These include multi-modality image display; 3D-3D rigid and deformable
      registration to bring preoperative image and planning data to the most up-to-date
      CBCT; 3D-2D registration of planning and image data to real-time fluoroscopy;
      infrared, electromagnetic, and video-based trackers used individually or in
      hybrid arrangements; augmented overlay of image and planning data in endoscopic
      or in-room video; and real-time "virtual fluoroscopy" computed from GPU
      accelerated digitally reconstructed radiographs (DRRs). Application in three
      preclinical scenarios (temporal bone, skull base, and spine surgery) demonstrates
      the utility of the modular, task-specific approach in progressively complex
      tasks. CONCLUSIONS: The design and development of a system architecture for image
      guided surgery has been reported, demonstrating enhanced utilization of
      intraoperative CBCT in surgical applications with vastly different requirements.
      The system integrates C-arm CBCT with a broad variety of data sources in a
      modular fashion that streamlines the interface to application-specific tools,
      accommodates distinct workflow scenarios, and accelerates testing and translation
      of novel toolsets to clinical use. The modular architecture was shown to adapt to
      and satisfy the requirements of distinct surgical scenarios from a common code
      base, leveraging software components arising from over a decade of effort within
      the imaging and computer-assisted interventions community.

PMID- 21744086
TI  - Identification of a novel bacterial K(+) channel.
AB  - In an attempt to explore unknown K(+) channels in mammalian cells, especially ATP
      sensitive K(+) (K(ATP)) channels, we compared the sequence homology of Kir6.1 and
      Kir6.2, two pore-forming subunits of mammalian K(ATP) channel genes, with
      bacterial genes that code for selective proteins with confirmed or putative ion
      transport properties. BLAST analysis revealed that a prokaryotic gene (ydfJ)
      expressed in Escherichia coli K12 strain shared 8.6% homology with Kir6.1 and
      8.3% with Kir6.2 genes. Subsequently, we cloned and sequenced ydfJ gene from E.
      coli K12 and heterologously expressed it in mammalian HEK-293 cells. The whole
      cell patch-clamp technique was used to record ion channel currents generated by
      ydfJ-encoded protein. Heterologous expression of ydfJ gene in HEK-293 cells
      yielded a novel K(+) channel current that was inwardly rectified and had a
      reversal potential close to K(+) equilibrium potential. The expressed ydfJ
      channel was blocked reversibly by low concentration of barium in a dose-dependent
      fashion. Specific K(ATP) channel openers or blockers did not alter the K(+)
      current generated by ydfJ expression alone or ydfJ coexpressed with rvSUR1 or
      rvSUR2B subunits of K(ATP) channel complex. Furthermore, this coexpressed
      ydfJ/rvSUR1 channels were not inhibited by ATP dialysis. On the other hand, ydfJ
      K(+) currents were inhibited by protopine (a nonspecific K(+) channel blocker)
      but not by dofetilide (a HERG channel blocker). In summary, heterologously
      expressed prokaryotic ydfJ gene formed a novel functional K(+) channel in
      mammalian cells.

PMID- 21744087
TI  - The relative timing between eye and hand in rapid sequential pointing is affected
      by time pressure, but not by advance knowledge.
AB  - The present study examined the effect of timing constraints and advance knowledge
      on eye-hand coordination strategy in a sequential pointing task. Participants
      were required to point at two successively appearing targets on a screen while
      the inter-stimulus interval (ISI) and the trial order were manipulated, such that
      timing constraints were high (ISI = 300 ms) or low (ISI = 450 ms) and advance
      knowledge of the target location was present (fixed order) or absent (random
      order). Analysis of eye and finger onset and completion times per segment of the
      sequence indicated that oculo-manual behaviour was in general characterized by
      eye movements preceding the finger, as well as 'gaze anchoring' (i.e. eye
      fixation of the first target until completion of the finger movement towards that
      target). Advance knowledge of future target locations lead to shorter latency
      times of eye and hand, and smaller eye-hand lead times, which in combination
      resulted in shorter total movement times. There was, however, no effect of
      advance knowledge on the duration of gaze anchoring. In contrast, gaze anchoring
      did change as a function of the interval between successive stimuli and was
      shorter with a 300 ms ISI versus 450 ms ISI. Further correlation analysis
      provided some indication that shorter residual latency is associated with shorter
      pointing duration, without affecting accuracy. These results are consistent with
      a neural mechanism governing the coupling of eye and arm movements, which has
      been suggested to reside in the superior colliculus. The temporal coordination
      resulting from this coupling is a function of the time pressure on the visuo
      manual system resulting from the appearance of external stimuli.

PMID- 21744088
TI  - Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic
      kidney disease: SSTR5 polymorphism and PKD1 mutation.
AB  - A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD)
      presented with acromegaly and a pituitary macroadenoma. There was a family
      history of this renal disorder. She had undergone surgery for pituitary adenoma 6
      years prior. Physical examination disclosed bitemporal hemianopsia and elevation
      of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth
      factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance
      imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic
      chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic,
      molecular and in silico analysis was undertaken. Histologic, immunohistochemical
      and ultrastructural studies of the lesion disclosed a sparsely granulated
      somatotroph adenoma. Standard chromosome analysis on the blood sample showed no
      abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing
      DNA from both peripheral leukocytes and the tumor revealed the most common PKD1
      mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant
      c.142C>A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor,
      while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2
      genes. To our knowledge, this is the fourth reported case of a GH-producing
      pituitary adenoma associated with ADPKD, but the first subjected to extensive
      morphological, ultrastructural, cytogenetic and molecular studies. The physical
      proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal
      relationship between ADPKD and somatotroph adenoma.

PMID- 21744089
TI  - A quantitative assessment of alkaptonuria: testing the reliability of two disease
      severity scoring systems.
AB  - Alkaptonuria (AKU) is due to excessive homogentisic acid accumulation in body
      fluids due to lack of enzyme homogentisate dioxygenase leading in turn to varied
      clinical manifestations mainly by a process of conversion of HGA to a polymeric
      melanin-like pigment known as ochronosis. A potential treatment, a drug called
      nitisinone, to decrease formation of HGA is available. However, successful
      demonstration of its efficacy in modifying the natural history of AKU requires an
      effective quantitative assessment tool. We have described two potential tools
      that could be used to quantitate disease burden in AKU. One tool describes
      scoring the clinical features that includes clinical assessments, investigations
      and questionnaires in 15 patients with AKU. The second tool describes a scoring
      system that only includes items obtained from questionnaires used in 44 people
      with AKU. Statistical analyses were carried out on the two patient datasets to
      assess the AKU tools; these included the calculation of Chronbach's alpha,
      multidimensional scaling and simple linear regression analysis. The conclusion
      was that there was good evidence that the tools could be adopted as AKU
      assessment tools, but perhaps with further refinement before being used in the
      practical setting of a clinical trial.

PMID- 21744090
TI  - Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis
      and management.
AB  - The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused
      by the absence of functional enzymes that contribute to the degradation of
      glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in
      multi-organ system dysfunction that varies with the particular GAG deposited and
      the specific enzyme mutation(s) present. Cardiac involvement has been reported in
      all MPS syndromes and is a common and early feature, particularly for those with
      MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left
      sided than for right-sided valves), and hypertrophy are commonly present;
      conduction abnormalities, coronary artery and other vascular involvement may also
      occur. Cardiac disease emerges silently and contributes significantly to early
      mortality.The clinical examination of individuals with MPS is often difficult due
      to physical and, sometimes, intellectual patient limitations. The absence of
      precordial murmurs does not exclude the presence of cardiac disease.
      Echocardiography and electrocardiography are key diagnostic techniques for
      evaluation of valves, ventricular dimensions and function, which are recommended
      on a regular basis. The optimal technique for evaluation of coronary artery
      involvement remains unsettled.Standard medical and surgical techniques can be
      modified for MPS patients, and systemic therapies such as hematopoietic stem cell
      transplantation and enzyme replacement therapy (ERT) may alter overall disease
      progression with regression of ventricular hypertrophy and maintenance of
      ventricular function. Cardiac valve disease is usually unresponsive or, at best,
      stabilized, although ERT within the first few months of life may prevent valve
      involvement, a fact that emphasizes the importance of early diagnosis and
      treatment in MPS.

PMID- 21744091
TI  - Apical meristem exhaustion during determinate primary root growth in the moots
      koom 1 mutant of Arabidopsis thaliana.
AB  - An indeterminate developmental program allows plant organs to grow continuously
      by maintaining functional meristems over time. The molecular mechanisms involved
      in the maintenance of the root apical meristem are not completely understood. We
      have identified a new Arabidopsis thaliana mutant named moots koom 1 (mko1) that
      showed complete root apical meristem exhaustion of the primary root by 9 days
      post-germination. MKO1 is essential for maintenance of root cell proliferation.
      In the mutant, cell division is uncoupled from cell growth in the region
      corresponding to the root apical meristem. We established the sequence of
      cellular events that lead to meristem exhaustion in this mutant. Interestingly,
      the SCR and WOX5 promoters were active in the mko1 quiescent center at all
      developmental stages. However, during meristem exhaustion, the mutant root tip
      showed defects in starch accumulation in the columella and changes in auxin
      response pattern. Therefore, contrary to many described mutants, the determinate
      growth in mko1 seedlings does not appear to be a consequence of incorrect
      establishment or affected maintenance of the quiescent center but rather of cell
      proliferation defects both in stem cell niche and in the rest of the apical
      meristem. Our results support a model whereby the MKO1 gene plays an important
      role in the maintenance of the root apical meristem proliferative capacity and
      indeterminate root growth, which apparently acts independently of the SCR/SHR and
      WOX5 regulatory pathways.

PMID- 21744092
TI  - Up-regulation of leucine aminopeptidase-A in cadmium-treated tomato roots.
AB  - The effects of cadmium (Cd) on aminopeptidase (AP) activities and Leucine-AP
      (LAP) expression were investigated in the roots of tomato (Solanum lycopersicum
      L., var Ibiza) plants. Three-week-old plants were grown for 10 days in the
      presence of 0.3-300 MUM Cd and compared to control plants grown in the absence of
      Cd. AP activities were measured using six different p-nitroanilide (p-NA)
      substrates. Leu, Met, Arg, Pro and Lys hydrolyzing activities increased in roots
      of Cd-treated plants, while Phe-pNA cleavage was not enhanced after Cd
      treatments. The use of peptidase inhibitors showed that most of the Leu-pNA
      hydrolyzing activity was related to one or several metallo-APs. Changes in Lap
      transcripts, protein and activities were measured in the roots of 0 and 30-MUM Cd
      treated plants. LapA transcript levels increased in Cd-treated roots, whereas
      LapN RNAs levels were not modified. To assess amount of Leu-pNA hydrolyzing
      activity associated with the hexameric LAPs, LAP activity was measured following
      immunoprecipitation with a LAP polyclonal antiserum. LAP activity increased in Cd
      treated roots. There was a corresponding increase in LAP-A protein levels
      detected in 2D-immunoblots. The role of LAP-A in the proteolytic response to Cd
      stress is discussed.

PMID- 21744093
TI  - Analysis of the expression of BohLOL1, which encodes an LSD1-like zinc finger
      protein in Bambusa oldhamii.
AB  - A cDNA, BohLOL1, encoding a protein containing three zf-LSD1 (zinc finger-Lesions
      Simulating Disease resistance 1) domains was cloned from growing bamboo (Bambusa
      oldhamii) shoots. A phylogenetic analysis revealed that BohLOL1 is a homolog of
      Arabidopsis LSD1 and LOL1 (LSD-one-like 1), which have been reported to act
      antagonistically in controlling cell death via the maintenance of reactive oxygen
      species homeostasis. The BohLOL1 gene was differentially expressed in various
      bamboo shoot tissues and was upregulated in shoots with higher rates of culm
      elongation. The expression level of this gene in multiple shoots of bamboo, which
      were cultured in vitro, was also upregulated by auxins, cytokinins, pathogen
      infection, 2,6-dichloroisonicotinic acid (a functional analog of salicylic acid),
      and hydrogen peroxide. The results suggest that BohLOL1 participates in bamboo
      growth and in the response to biotic stress. The DNA-binding assays and
      subcellular localization studies demonstrated that BohLOL1 is a nuclear DNA
      binding protein. BohLOL1 might function through protein-DNA interactions and thus
      affect the expression of its target genes. The results of this study extend the
      role of plant LSD1 and LOL1 proteins from the regulation of cell death to cell
      growth. The growth-dependent up-regulation of BohLOL1 expression, which uniquely
      occurs in growing bamboo, might be one of the critical factors that contribute to
      the rapid growth of this remarkable plant.

PMID- 21744094
TI  - Medical history and the risk of biliary tract cancers in Shanghai, China:
      implications for a role of inflammation.
AB  - Several lines of evidence suggest that inflammation may play a role in the
      etiology of biliary tract cancers. To examine further the role of inflammation,
      we evaluated the associations between self-reported inflammatory-related medical
      conditions and the risk of biliary tract cancers in a population-based case
      control study in Shanghai, China. Our analysis included 368 gallbladder cancer
      cases, 191 bile duct cancer cases, 68 ampulla of Vater cancer cases, and 959
      healthy subjects. We used logistic regression to estimate odds ratios (ORs) and
      95% confidence intervals (CIs) for biliary tract cancers in relation to six
      inflammation-related conditions. Gallbladder cancer was significantly associated
      with cholecystitis occurring at least 5 years prior to interview (OR = 1.7, 95%
      CI 1.1-2.9). Even though biliary stones did not significantly modify the
      associations between cholecystitis and gallbladder cancer, 90% of the gallbladder
      cancer cases with cholecystitis also had biliary stones, indicating that stones
      likely play an important role in the link between cholecystitis and gallbladder
      cancer. Among subjects who smoked and drank alcohol, a history of gastric (OR =
      4.3, 95% CI 1.2-15.0) or duodenal ulcers (OR = 3.7, 1.2-12.0) was associated with
      an excess risk of gallbladder cancer. Although the mechanisms are unclear, our
      results further support the role for inflammation in the etiology of biliary
      tract cancers.

PMID- 21744096
TI  - Multi-detector row computed tomography (MDCT) is useful for the diagnosis of
      rectal varices.

PMID- 21744095
TI  - An examination of male and female odds ratios by BMI, cigarette smoking, and
      alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled
      data from 15 case-control studies.
AB  - BACKGROUND: Greater tobacco smoking and alcohol consumption and lower body mass
      index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal,
      hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex
      specific comparisons of ORs for these factors. METHODS: We analyzed 2,441 oral
      cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508
      hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men)
      cases from the INHANCE consortium of 15 head and neck cancer case-control
      studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis.
      Analyses fitted linear-exponential excess ORs models. RESULTS: ORs were increased
      in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in
      overweight and obese categories (>= 25 BMI) for all sites and were homogeneous by
      sex. ORs by smoking and drinking in women compared with men were significantly
      greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for
      hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for
      oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72)
      cancers. CONCLUSIONS: The extent that OR modifications of smoking and drinking by
      sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true
      associations, or derive from unmeasured confounders or unobserved sex-related
      disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer)
      remains to be clarified.

PMID- 21744097
TI  - Wide local excision for Buschke-Lowenstein tumor or circumferential carcinoma in
      situ.
AB  - PURPOSE: This study aimed to evaluate the outcome of patients with Buschke
      Lowenstein tumor or circumferential anal carcinoma in situ who underwent wide
      local excision with flap or skin graft coverage of the wound. METHODS: A
      retrospective review was conducted of all patients operated at Kaiser Permanente
      Los Angeles Medical Center during a 6-year period. Outcome measures included
      postoperative complications, functional results, recurrence rate, and re
      intervention rate. RESULTS: Of 152 patients operated for dysplastic anal lesions
      or tumors, 10 (7%) underwent wide local excision for Buschke-Lowenstein tumor or
      circumferential anal carcinoma in situ [men 70%, mean age 36 years]. Median
      duration of symptoms was 5 years. Eighty percent of patients had prior operations
      and 50% were positive for the human immunodeficiency virus. Mean size of the
      lesion was 41 cm(2). Microscopic margin positivity was noted in 60%. Wound was
      closed with house advancement flap in majority of patients. Only one patient had
      fecal diversion. Median length of stay was 2 days. Postoperative complications
      were noted in 50% of patients. Rate of transient postoperative incontinence was
      30%. Recurrent disease was noted in 3 patients with the human immunodeficiency
      virus [median follow-up: 18 months]. All recurrences were treated with local
      fulguration or medication. CONCLUSION: Wide local excision with flap or skin
      graft coverage is an option for patients with Buschke-Lowenstein tumor or
      circumferential anal carcinoma in situ. Close postoperative surveillance is
      advised due to the risk of recurrent disease, especially in patients with the
      human immunodeficiency virus.

PMID- 21744098
TI  - Does a learning curve exist in endorectal two-dimensional ultrasound accuracy?
AB  - BACKGROUND: Aim of the study was to assess adequacy of Colorectal Surgical
      Society of Australia and New Zealand (CSSANZ) endorectal ultrasound (ERUS)
      training and whether a subsequent learning curve exists. METHODS: A prospective
      audit of ERUS for staging rectal cancer by a single surgeon from commencement of
      consultant practice was performed. Data were recorded in a prospectively
      maintained database. The audit commenced on completion of CSSANZ training. T- and
      N-stage were assessed clinically, then by ERUS prior to treatment and finally by
      histology over 8 years. RESULTS: The results were compared over three time
      periods: the first a single year, then two three-year periods. Two hundred and
      seventy-two patients were examined. Two hundred and thirty-three were assessable
      for T-stage (13 no tumour excision, 26 long course pre-operative radiotherapy)
      and 142 for N-stage (74 endoanal excision, 17 proximal mesorectum un-assessable).
      Overall accuracy was 82% for T-stage and 73% for N-stage. Accuracy for T- and N
      staging did not change significantly over the three time periods (T: 82.1, 82.3,
      81.6%, P = 0.14; N: 83.3, 67.9, 74.2%, P = 0.31). The utility of ERUS was
      demonstrated by clinical assessment not being possible in 32% of cases and where
      the two modalities disagreed was correct 82% of the time. CONCLUSIONS: Endorectal
      ultrasound rectal cancer staging is accurate for T-stage. Competency in ERUS can
      be achieved in the CSSANZ fellowship and accuracy does not improve with further
      experience. An ERUS accreditation scheme should be established for future
      trainees.

PMID- 21744099
TI  - Modeling the dispersion of Ambrosia artemisiifolia L. pollen with the model
      system COSMO-ART.
AB  - Common ragweed (Ambrosia artemisiifolia L.) is a highly allergenic plant that is
      spreading throughout Europe. Ragweed pollen can be transported over large
      distances by the wind. Even low pollen concentrations of less than 10 pollen m(
      3) can lead to health problems in sensitive persons. Therefore, forecasting the
      airborne concentrations of ragweed pollen is becoming more and more important for
      public health. The question remains whether distant pollen sources need to be
      considered in reliable forecasts. We used the extended numerical weather
      prediction system COSMO-ART to simulate the release and transport of ragweed
      pollen in central Europe. A pollen episode (September 12-16, 2006) in north
      eastern Germany was modeled in order to find out where the pollen originated. For
      this purpose, several different source regions were taken into account and their
      individual impact on the daily mean pollen concentration and the performance of
      the forecast were studied with the means of a 2 * 2 contingency table and skill
      scores. It was found that the majority of the pollen originated in local areas,
      but up to 20% of the total pollen load came from distant sources in Hungary. It
      is concluded that long-distance transport should not be neglected when predicting
      pollen concentrations.

PMID- 21744100
TI  - Atmospheric conditions, lunar phases, and childbirth: a multivariate analysis.
AB  - Our objective was to assess extrinsic influences upon childbirth. In a cohort of
      1,826 days containing 17,417 childbirths among them 13,252 spontaneous labor
      admissions, we studied the influence of environment upon the high incidence of
      labor (defined by 75th percentile or higher), analyzed by logistic regression.
      The predictors of high labor admission included increases in outdoor temperature
      (odds ratio: 1.742, P = 0.045, 95%CI: 1.011 to 3.001), and decreases in
      atmospheric pressure (odds ratio: 1.269, P = 0.029, 95%CI: 1.055 to 1.483). In
      contrast, increases in tidal range were associated with a lower probability of
      high admission (odds ratio: 0.762, P = 0.030, 95%CI: 0.515 to 0.999). Lunar phase
      was not a predictor of high labor admission (P = 0.339). Using multivariate
      analysis, increases in temperature and decreases in atmospheric pressure
      predicted high labor admission, and increases of tidal range, as a measurement of
      the lunar gravitational force, predicted a lower probability of high admission.

PMID- 21744101
TI  - Refixation after lateral meniscus tear followed by complete luxation in an 11
      year-old.
AB  - Isolated meniscus tears with consecutive complete luxation of the meniscus are an
      exceptional injury especially in children. We report a case of an 11-year-old
      girl with a complete luxation of the lateral meniscus, injured by a jump from low
      height. Following clinical examination and magnetic resonance imaging, a surgical
      refixation of the entire lateral meniscus was performed. Short-time clinical and
      radiological follow-up was conducted.

PMID- 21744102
TI  - The osteogenic differentiation of dog bone marrow mesenchymal stem cells in a
      thermo-sensitive injectable chitosan/collagen/beta-glycerophosphate hydrogel: in
      vitro and in vivo.
AB  - Type I collagen was added to the composite chitosan solution in a ratio of 1:2 to
      build a physical cross-linked self-forming chitosan/collagen/beta-GP hydrogel.
      Osteogenic properties of this novel injectable hydrogel were evaluated. Gelation
      time was about 8 min which offered enough time for handling a mixture containing
      cells and the subsequent injection. Scanning electronic microscopy (SEM)
      observations indicated good spreading of bone marrow mesenchymal stem cells
      (BMSCs) in this hydrogel scaffold. Mineral nodules were found in the dog-BMSCs
      inoculated hydrogel by SEM after 28 days. After subcutaneous injection into nude
      mouse dorsum for 4 weeks, partial bone formation was observed in the
      chitosan/collagen/beta-GP hydrogel loaded with pre-osteodifferentiated dog-BMSCs,
      which indicated that chitosan/collagen/beta-GP hydrogel composite could induce
      osteodifferentiation in BMSCs without exposure to a continual supply of external
      osteogenic factors. In conclusion, the novel chitosan/collagen/beta-GP hydrogel
      composite should prove useful as a bone regeneration scaffold.

PMID- 21744103
TI  - Delivery of chemotropic proteins and improvement of dopaminergic neuron outgrowth
      through a thixotropic hybrid nano-gel.
AB  - Chemotropic proteins guide neuronal projections to their final target during
      embryo development and are useful to guide axons of neurons used in
      transplantation therapies. Site-specific delivery of the proteins however is
      needed for their application in the brain to avoid degradation and pleiotropic
      affects. In the present study we report the use of Poly (ethylene glycol)-Silica
      (PEG-Si) nanocomposite gel with thixotropic properties that make it injectable
      and suitable for delivery of the chemotropic protein semaphorin 3A. PEG-Si gel
      forms a functional gradient of semaphorin that enhances axon outgrowth of
      dopaminergic neurons from rat embryos or differentiated from stem cells in
      culture. It is not cytotoxic and its properties allowed its injection into the
      striatum without inflammatory response in the short term. Long term implantation
      however led to an increase in macrophages and glial cells. The inflammatory
      response could have resulted from non-degraded silica particles, as observed in
      biodegradation assays.

PMID- 21744104
TI  - Oxygen consumption, acidification and migration capacity of human primary
      osteoblasts within a three-dimensional tantalum scaffold.
AB  - A major clinical problem within synthetic, large-scaled scaffolds is the
      insufficient nutrient supply resulting in inhomogeneous cell proliferation and
      differentiation. The aim of this study was to analyse pH value, oxygen
      consumption and migration of human osteoblasts within a 3D tantalum scaffold,
      clinically used for larger bone defects. After 24 h the oxygen concentration
      within the scaffold decreased significantly and remained low during incubation.
      Monitoring of the pH value inside the tantalum scaffold showed a slightly
      acidification under static culture conditions. However, cell migration within the
      3D scaffold was detected. Hence, in clinical application it can be assumed that
      porous tantalum scaffolds can be settled by osteoblasts under critical oxygen and
      nutrient supply. In general, monitoring of cell migration, oxygen consumption and
      acidification can be a suitable instrument for creating advanced 3D bone
      scaffolds.

PMID- 21744105
TI  - Carcinoma ex pleomorphic adenoma: a comprehensive review of clinical,
      pathological and molecular data.
AB  - Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma arising from a primary
      or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to
      clinicians and pathologists. This study intends to review the literature and
      highlight the current clinical and molecular perspectives about this entity. The
      most common clinical presentation of CA ex PA is of a firm mass in the parotid
      gland. The proportion of adenoma and carcinoma components determines the
      macroscopic features of this neoplasm. The entity is difficult to diagnose pre
      operatively. Pathologic assessment is the gold standard for making the diagnosis.
      Treatment for Ca ex PA often involves an ablative surgical procedure which may be
      followed by radiotherapy. Overall, patients with Ca ex PA have a poor prognosis.
      Accurate diagnosis and aggressive surgical management of patients presenting with
      Ca ex PA can increase their survival rates. Molecular studies have revealed that
      the development of Ca ex PA follows a multi-step model of carcinogenesis, with
      the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and
      finally 17p. There are specific candidate genes in these regions that are
      associated with particular stages in the progression of Ca ex PA. In addition,
      many genes which regulate tumour suppression, cell cycle control, growth factors
      and cell-cell adhesion play a role in the development and progression of Ca ex
      PA. It is hopeful that these molecular data can give clues for the diagnosis and
      management of the disease.

PMID- 21744106
TI  - Focal osseous dysplasia.
AB  - Focal osseous dysplasia (FOD) is one of the benign fibro-osseous lesions of the
      jaw bones and the most commonly occuring benign fibro-osseous lesion. This entity
      occurs more commonly in females and has a predilection for African Americans.
      Radiographically, the lesion has a variable appearance depending on the duration
      but may appear as a radiolucent to radiopaque lesion that can be well to poorly
      defined. Hisotologically, when biopsied, there are fragments of bony trabeculae
      intermixed with fibrous stroma with incomplete stromal vasculature. The main
      differential diagnosis is with ossifying fibroma, which is neoplastic while FOD
      is considered a reactive process. Most patients with FOD may be followed
      clinically without surgical intervention.

PMID- 21744107
TI  - Topiramate related reversible erectile dysfunction in temporal lobe epilepsy.
AB  - Topiramate (TPM) is a newer antiepileptic drug with high efficacy in treating
      various neurological disorders, especially epilepsy and migraine. The adverse
      effects of TPM therapy are mainly central nervous system-related somnolence and
      dizziness. There are rare reports about the role of TPM on sexual effects, but
      with inconsistent results. In this report, we describe a 31-year-old man who
      developed erectile dysfunction after several months of TPM use. Complete
      urological and sexual psychiatric evaluations were done. There was lack of an
      identifiable organic basis and psychiatric pathology in this patient. The
      erectile dysfunction improved only after the termination of TPM, documenting the
      temporal relationship. We reviewed and discussed the clinical aspect of TPM use
      in erectile dysfunction. This case and the rare cases of erectile dysfunction in
      TPM use reported in the literature show that TPM is worth to be paid attention to
      whenever it is prescribed in a wide range of neurological disorders.

PMID- 21744108
TI  - Neurodegeneration in the course of Langerhans cell histiocytosis.
AB  - Cerebral involvement in the course of Langerhans cell histiocytosis has been
      described especially in children. It is mainly characterized by hypothalamic
      pituitary functional deficit, due to granuloma growth. Here we describe a rare
      case of adult-onset histiocytosis developing a neurodegenerative disease
      resembling multiple system atrophy. The patient we describe here started
      suffering from subtle personality changes which progressed to a severe
      neurological syndrome 2 years after the diagnosis of histiocytosis. Twenty years
      before she developed a diabetes insipidus, without any apparent cause. Brain MRI
      scans at the time of neurodegeneration revealed slight signal alterations at the
      cerebellum, especially involving the dentate nuclei and the white matter. Despite
      being rare, histiocytosis should be considered in adult patients with cerebellar
      abnormalities and/or with unexplained diabetes insipidus to rapidly discern and
      treat histiocytosis before the onset of its neurodegenerative, untreatable phase.

PMID- 21744109
TI  - Uncertainties in the measurement of blood glucose in paediatric intensive care:
      implications for clinical trials of tight glycaemic control.
AB  - PURPOSE: In preparation for a tight glycaemic control (TGC) clinical trial we
      assessed the agreement between methods used to measure blood glucose in
      critically ill children. METHODS: Service evaluation comparing blood gas and main
      laboratory analysers with point-of-care (POC) devices PCX, ACCU-Chek and Hemocue.
      RESULTS: Two hundred forty-five samples from 157 children measured on 2-4 devices
      provided 790 values. Marked variation was evident in glucose values between
      devices, time between tests, sample (whole blood/plasma) and source; 39% of
      paired values had >20% difference. The decision to start insulin at 7 mmol/L
      differed depending on the device used for 33% of samples. At low glucose values
      (<4 mmol/L), differences up to 1.8 mmol/L were evident. The blood gas analyser
      read lower than all POC models and the laboratory analyser (less risk of
      undetected hypoglycaemia). An inverse relationship was evident between
      haematocrit (Hct) and glucose error using POC devices. PCX values for samples
      with Hct <30% were higher (85%), whereas those for Hct values >38% were lower
      (66%). Glycolysis occurred during transfer of samples to the laboratory. Using
      the PCX at the bedside resulted in 0.5 mmol/L mean difference higher than
      laboratory values; locating the PCX in the laboratory reduced this to 0.2 mmol/L.
      CONCLUSIONS: Discrepancies between measurements may mask hypoglycaemia, and the
      potential benefits of controlling hyperglycaemia may not be achieved. Variation
      introduced by different devices, sample or source may have led to
      misclassification of treatment decisions contributing to the conflicting results
      of TGC studies.

PMID- 21744110
TI  - Identification and characterization of a Streptomyces sp. isolate exhibiting
      activity against multidrug-resistant coagulase-negative Staphylococci.
AB  - The resistance of 220 coagulase-negative Staphylococci (CNS) (associated with
      animal disease) to 13 antibiotics were determined using the disk diffusion
      method. 35.9% of multidrug-resistant coagulase-negative Staphylococci (MR-CNS)
      exhibited resistance to five or more than five antibiotics; all of these bacteria
      were resistant to methicillin too. The new Streptomyces sp. ABRIINW111 was
      isolated from the Zagros Mountains Hamadan, Iran. The 16S rDNA sequence of the
      isolate indicated that it has 98% similarity to S. levis, but some mutations in
      the alpha and gamma regions of the 16S rDNA sequence emphasize the probability of
      the existence of a new species. Preliminary and secondary antibacterial
      screenings revealed that the isolate is active against gram negative and positive
      bacteria. The diethyl ether extracted metabolite of the Streptomyces sp.
      ABRIINW111 showed an effective antibacterial activity against MR-CNS. So the
      diethyl ether extract of the new Streptomyces sp. strain ABRIINW111 can inhibit
      the MR-CNS in vitro, and it can offer a new approach to treat MR-CNS infectious
      patients.

PMID- 21744111
TI  - Standardization of the outbred BALB/c mice as a suitable animal model for
      Besnoitia caprae studies.
AB  - The Apicomplexan parasite Besnoitia caprae infects wild and domestic goats.
      Knowledge on Besnoitia caprae specially an optimized animal model is sparse.
      Experimental infections with tachyzoites of BC-Pars obtained from BALB/c mice
      were conducted in outbred mice to determine the infectivity and LD50 of Besnoitia
      caprae. Six groups of five mice were intraperitoneally infected with 12.5 *
      10(3), 25 * 10(3), 5 * 10(4), 1 * 10(5) and 2 * 10(5) tachyzoites and a control
      inoculum of DMEM, respectively. Although morbidity and mortality were observed in
      all groups, two mice in the 12.5 * 10(3) group showed alopecia and skin lesions
      on 60 days post-infection (DPI). Histopathological and molecular examination of
      skins confirmed B. caprae infection. The LD50 was calculated as 25 * 10(3.2)
      tachyzoites per mouse. The results indicate that outbred BALB/c mice can be used
      as a suitable model of besnoitiosis and to screen candidate treatments and to
      test the efficacy of vaccines for besnoitiosis.

PMID- 21744112
TI  - Brain perfusion correlates of cognitive and nigrostriatal functions in de novo
      Parkinson's disease.
AB  - PURPOSE: Subtle cognitive impairment is recognized in the first stages of
      Parkinson's disease (PD), including executive, memory and visuospatial
      dysfunction, but its pathophysiological basis is still debated. METHODS: Twenty
      six consecutive, drug-naive, de novo PD patients underwent an extended
      neuropsychological battery, dopamine transporter (DAT) and brain perfusion single
      photon emission computed tomography (SPECT). We previously reported that
      nigrocaudate impairment correlates with executive functions, and nigroputaminal
      impairment with visuospatial abilities. Here perfusion SPECT was first compared
      between the PD group and age-matched controls (CTR). Then, perfusion SPECT was
      correlated with both DAT SPECT and four neuropsychological factors by means of
      voxel-based analysis (SPM8) with a height threshold of p < 0.005 at peak level
      and p < 0.05 false discovery rate-corrected at cluster level. Both perfusion and
      DAT SPECT images were flipped in order to have the more affected hemisphere
      (MAH), defined clinically, on the same side. RESULTS: Significant hypoperfusion
      was found in an occipital area of the MAH in PD patients as compared to CTR.
      Executive functions directly correlated with brain perfusion in bilateral
      posterior cingulate cortex and precuneus in the less affected hemisphere (LAH),
      while verbal memory directly correlated with perfusion in the precuneus, inferior
      parietal lobule and superior temporal gyrus in the LAH. Furthermore, positive
      correlation was highlighted between nigrocaudate and nigroputaminal impairment
      and brain perfusion in the precuneus, posterior cingulate and parahippocampal
      gyri of the LAH. CONCLUSION: These data support the evidence showing an early
      involvement of the cholinergic system in the early cognitive dysfunction and
      point to a more relevant role of parietal lobes and posterior cingulate in
      executive functions in PD.

PMID- 21744113
TI  - Symptom experience during acute coronary syndrome and the development of
      posttraumatic stress symptoms.
AB  - There is growing evidence for the development of posttraumatic stress symptoms as
      a consequence of acute cardiac events. Acute coronary syndrome (ACS) patients
      experience a range of acute cardiac symptoms, and these may cluster together in
      specific patterns. The objectives of this study were to establish distinct
      symptom clusters in ACS patients, and to investigate whether the experience of
      different types of symptom clusters are associated with posttraumatic symptom
      intensity at six months. ACS patients were interviewed in hospital within 48 h of
      admission, 294 patients provided information on symptoms before hospitalisation,
      and cluster analysis was used to identify patterns. Posttraumatic stress symptoms
      were assessed in 156 patients at six months. Three symptom clusters were
      identified; pain symptoms, diffuse symptoms and symptoms of dyspnea. In multiple
      regression analyses, adjusting for sociodemographic, clinical and psychological
      factors, the pain symptoms cluster (beta = .153, P = .044) emerged as a
      significant predictor of posttraumatic symptom severity at six months. A
      marginally significant association was observed between symptoms of dyspnea and
      reduced intrusive symptoms at six months (beta = -.156, P = .061). Findings
      suggest acute ACS symptoms occur in distinct clusters, which may have distinctive
      effects on intensity of subsequent posttraumatic symptoms. Since posttraumatic
      stress is associated with adverse outcomes, identifying patients at risk based on
      their symptom experience during ACS may be useful in targeting interventions.

PMID- 21744114
TI  - Positive selection of Toll-like receptor 2 polymorphisms in two closely related
      old world monkey species, rhesus and Japanese macaques.
AB  - Toll-like receptor 2 (TLR2) plays an important role in the recognition of a
      variety of pathogenic microbes. In the present study, we compared polymorphisms
      of TLR2 locus in two closely related old world monkey species, rhesus monkey
      (Macaca mulatta) and Japanese monkey (Macaca fuscata). By nucleotide sequencing
      of the third exon of TLR2 gene from 21 to 35 respective individuals, we could
      assign 17 haplotype combinations of 17 coding SNPs of ten non-synonymous and
      seven synonymous substitutions. A non-synonymous substitution at codon position
      326 appeared to be differentially fixed in each species, asparagine for M.
      mulatta whereas tyrosine for M. fuscata, and may contribute to certain functional
      properties because it locates in the region contributing to ligand binding and
      interaction with dimerization partner of TLR2-TLR1 heterodimeric complex.
      Although TLR2 alleles have diverged to similar extent in both species, they have
      evolved in significantly different ways; TLR2 of M. fuscata has undergone
      purifying selection while the membrane-proximal part of the extracellular domain
      of M. mulatta TLR2 exhibits higher rates of non-synonymous substitutions,
      indicating a trace of Darwinian positive selection.

PMID- 21744115
TI  - Understanding the influence of phosphatidylcholine on the molecular weight of
      hyaluronic acid synthesized by Streptococcus zooepidemicus.
AB  - The effect of phosphatidylcholine on the molecular weight properties of
      hyaluronic acid (HA) was studied in batch culture of Streptococcus zooepidemicus
      by adding phosphatidylcholine at the early stage of exponential phase. With the
      addition of 80 mg/L of phosphatidylcholine, maximum HA yield (2.47 g/L) and
      weight-average molecular weight (902.60 KDa) were achieved, increased by 17.4%
      and 67.1%, respectively, as compared to the control. Metabolic flux analysis was
      employed to study the mechanism of phosphatidylcholine on the molecular weight of
      HA. The normalized flux distribution maps based on fermentation data at
      phosphatidylcholine addition indicated that phosphatidylcholine resulted in
      higher flux flowing to the HA pathway and lower flux flowing to the glycolysis
      and biomass synthesis pathway, coupling with higher level of UDPNAG generation
      and extra regeneration of ATP. The GC-MS analysis of fatty acids in the plasma
      membrane showed that the addition of phosphatidylcholine could promote the
      mobility and permeability of the cell membrane, making the HA chain pass through
      the membrane more easily, thus decreasing the energy consumption. All these
      results led to higher molecular weight of hyaluronic acid.

PMID- 21744116
TI  - Expression and characterization of a novel lipase from Aspergillus fumigatus with
      high specific activity.
AB  - A novel lipase gene from Aspergillus fumigatus, afl1-1, was cloned and expressed
      with a molecular mass of 38 kDa in Escherichia coli for the first time. The
      recombinant lipase had a preference for short carbon chain p-nitrophenyl esters,
      especially toward C2 p-nitrophenyl ester and exhibited potent hydrolysis activity
      that had not been observed. The optimum pH and temperature of this new enzyme
      were 8.5 and 65  degrees C, respectively. The recombinant lipase (AFL1-1) is an
      alkaline enzyme which was stable in the pH range 6.0~8.5 for 16 h (at 4  degrees
      C) and at 30~50  degrees C for 1 h. It is an intracellular enzyme which was
      purified approximately 8.47-fold with an overall yield of 86.1% by single-step Ni
      NTA affinity purification, with a very high specific activity of approximately
      1.00 * 10(3) U mg(-1) on a standard substrate of p-nitrophenyl acetate. The
      Michaelis-Menten kinetic parameters V (max) and K (m) of the lipase were 1.37 mM
      mg(-1) min(-1) and 14.0 mM, respectively. Ca(2+) and other metal ions could not
      activate the lipase. According to the homology analysis and site-directed
      mutagenesis assay, the catalytic triad of the recombinant lipase was identified
      as Ser-165, Asp-260, and His-290 residues.

PMID- 21744117
TI  - Ethanolic extract of fructus Alpinia oxyphylla protects against 6-hydroxydopamine
      induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish.
AB  - In an attempt to understand the neuroprotective effect of Fructus Alpinia
      oxyphylla (AOE) and to elucidate its underlying mechanism of action, the
      ethanolic extract of AOE was investigated using zebrafish and PC12 cell models.
      AOE prevented and restored 6-hydroxydopamine (6-OHDA)-induced dopaminergic (DA)
      neuron degeneration and attenuated a deficit of locomotor activity in a zebrafish
      (Danio rerio) model of Parkinson's disease (PD). Treatment with AOE increased the
      viability of 6-OHDA-treated PC12 cells in vitro in a dose-dependent manner by
      attenuating cellular apoptosis. However, protocatechuic acid (PCA) and chrysin,
      two known polyphenol components of AOE, could not reproduce the neuroprotective
      activity of AOE in the PD zebrafish or PC12 cell models. A mechanistic study
      found that the protective effect of AOE against 6-OHDA-induced neuronal injury
      involved anti-inflammatory action (down-regulation of gene expression of IL-1beta
      and TNF-alpha) and anti-oxidative action (inhibition of NO production and iNOS
      expression in PC12 cells). Moreover, the PI3K-AKT pathway might be part of the
      mechanism of neuroprotection of AOE. The results of this research are expected to
      provide a scientific rationale for the use of AOE in the treatment of PD.
      However, it is important that the active components that contribute to the
      neuroprotective action of AOE are identified and characterized.

PMID- 21744118
TI  - HIV-1 effects on neuropsychological performance in a resource-limited country,
      Zambia.
AB  - Zambia has substantially been affected by the HIV/AIDS epidemic with prevalence
      rates at 14% in a population estimated at 12 million. Yet, the extent of HIV
      associated neurocognitive disorders (HAND) in this population remains to be
      clearly understood. A series of culturally appropriate neuropsychological (NP)
      assessments [International HIV Dementia Scale (IHDS), Color Trails Test 1 and 2,
      Grooved pegboard Test, and Time Gait Test] were used to test the effects of HIV
      on NP performance of HIV seropositive and seronegative individuals. Twenty-two
      percent HIV positive individuals ARV naive met the criteria for IHDS-defined NP
      impairment. Gender significantly influenced the performance on NP tests with
      females performing more poorly compared to males. Larger studies that will
      accommodate gender differences and age are necessary to generate appropriate
      norms in Zambia in order to better assess the prevalence of HAND in the
      developing country setting.

PMID- 21744119
TI  - Necrotizing tuberculosis with duodenal perforation as a primary manifestation of
      AIDS.

PMID- 21744120
TI  - Knockdown of NtMed8, a Med8-like gene, causes abnormal development of vegetative
      and floral organs in tobacco (Nicotiana tabacum L.).
AB  - Med8, a subunit of mediator complex, has proved to possess crucial functions in
      many organisms from yeast to human. In plant, the med8 mutant of Arabidopsis
      thaliana displayed delayed anthesis and increased number of leaves during the
      vegetative period. However, the roles of Med8 in other flowering plants are still
      unknown. To investigate the function of Med8 ortholog in tobacco (Nicotiana
      tabacum L.; named as NtMed8), we created transgenic tobacco plants with repressed
      NtMed8 expression mediated by RNA interference (RNAi). Compared with the wild
      type, the NtMed8-RNAi plants exhibited: more leaves with smaller but thicker
      blades; larger cells and vascular bundles with lower stomata density in leaves;
      swelled chloroplasts with thicker and lumen-enlarged thylakoids; weaker root
      system with fewer lateral roots; larger flowers and floral organs; flowering
      earlier under long day, but later under short day conditions; and male sterile
      with larger but less germinable pollens. In addition, quantitative RT-PCR
      indicated that NtMed8 is expressed in both vegetative and floral tissues.
      Subcellular localization analysis by transient expression of fusion protein in
      Nicotiana benthamiana leaves showed that NtMed8 was located in both plasma
      membrane and nucleus. These results suggest that NtMed8 plays important roles in
      both vegetative and reproductive development, and the function of Med8 appears to
      be, at least partially, conserved in flowering plants.

PMID- 21744121
TI  - Kinetic biosynthesis of L-ascorbyl acetate by immobilized Thermomyces lanuginosus
      lipase (Lipozyme TLIM).
AB  - Thermomyces lanuginosus lipase (Lipozyme TLIM)-catalyzed esterification of L
      ascorbic acid was studied. It was suggested that Lipozyme TLIM was a suitable
      biocatalyst for enzymatic esterification of L-ascorbic acid. Three solvents were
      investigated for the reaction, and acetone was found to be a suitable reaction
      medium. Furthermore, it was found that water activity could notably affect the
      conversion. Moreover, pH memory of Lipozyme TLIM lipase for catalyzing L-ascorbic
      acid esterification in acetone was observed and the effect of pH on the reaction
      was estimated. In addition, the influences of other parameters such as substrate
      mole ratio, enzyme loading, and reaction temperature and reusability of lipase on
      esterification of L-ascorbic acid were also analyzed systematically and
      quantitatively. Kinetic characterization of Lipozyme TLIM showed that K(m,a) and
      V(max) were 80.085 mM and 0.747 mM min(-1), respectively. As a result, Lipozyme
      TLIM-catalyzed esterification of L: -ascorbic acid gave a maximum conversion of
      99%.

PMID- 21744122
TI  - VEGF gene polymorphism and response to intravitreal bevacizumab and triple
      therapy in age-related macular degeneration.
AB  - PURPOSE: To investigate the association between the vascular endothelial growth
      factor (VEGF) gene and response to either intravitreal bevacizumab (IVB) or
      photodynamic therapy with intravitreal triamcinolone acetonide and IVB (triple
      therapy) for neovascular age-related macular degeneration (AMD). METHODS: The
      study consisted of 94 patients with neovascular AMD who underwent IVB and 79
      patients with neovascular AMD who underwent triple therapy. Genotypes were
      determined for four selected tagging single-nucleotide polymorphism (SNP)s of the
      VEGF gene. RESULTS: Of the four SNPs studied, one SNP (rs699946) was associated
      significantly with visual acuity (VA) changes 12 months after treatment
      irrespective of whether they received IVB alone (P = 0.044) or triple therapy
      0.010). Baseline VA was not significantly different among the three genotypes of
      rs699946 in either treatment group. There were no significant differences in the
      number of treatments, incidence of recurrence, or the period until the recurrence
      according to VEGF rs699946 genetic variant. CONCLUSIONS: The VEGF gene SNP
      rs699946 was associated with response to IVB alone and to triple therapy in this
      study. The G allele in SNP rs699946 can thus be applied as a marker for better
      visual prognosis in patients with neovascular AMD who receive either IVB or
      triple therapy.

PMID- 21744123
TI  - Lamellar macular hole formation in chronic cystoid macular edema associated with
      retinal vein occlusion.
AB  - PURPOSE: To report the formation of a lamellar macular hole (LMH) in four eyes
      with chronic cystoid macular edema (CME) associated with retinal vein occlusion
      (RVO). METHODS: We reviewed retrospectively the medical records of four patients
      with chronic CME associated with RVO, in whom LMH formation was observed by a
      series of examinations with optical coherence tomography. RESULTS: All eyes
      showed a large chronic cystoid space in the fovea. Three eyes showed an
      epiretinal membrane, and one eye showed traction of a posterior hyaloid membrane
      to the fovea. The chronic cystoid space changed into an LMH by rupture of its
      inner wall due to traction. After formation of the LMH, the mean total foveal
      thickness decreased from 590 +/- 131 to 95 +/- 22 MUm, equal to the thickness of
      the foveal photoreceptor layer before the formation of the LMH (mean 100 +/- 23
      MUm). Visual acuity did not change substantially from before to after the
      formation of the LMH. CONCLUSIONS: Chronic CME associated with RVO can transform
      into an LMH through the rupture of the inner wall of the foveal cystoid space.
      While this transformation is accompanied by a substantial reduction in macular
      thickness, it does not lead to changes in visual function.

PMID- 21744124
TI  - Development and long-term in vivo testing of a novel skin-button system for
      preventing driveline infection of an implantable VAD system.
AB  - Driveline infection is a serious complication in long-term therapy using a
      ventricular assist device (VAD). However, measures taken against this
      complication have not been sufficient. In this study, we evaluated our newly
      developed infection-resistant skin-button system against driveline infection of
      an implantable VAD in a chronic animal study. The skin button is made of two
      flanges using tissue-compatible segmented polyurethane. The exposed upper layer
      is made of a nonporous sheet with relative flexibility similar in texture to the
      skin. In addition, this shape was designed to defuse excessive stress at the edge
      of the skin caused by the external force put on the driveline. The lower layer,
      which is implanted subcutaneously, is made of a porous material with a three
      dimensional reticular structure. The combination of these two flanges with
      different features enables the driveline to fix to the skin without epithelial
      downgrowth and peridriveline pocket formation and can prevent bacterial infection
      over a prolonged period. Results of 90 days of animal tests, the button
      maintained secure adhesion to the skin and did not exfoliate without special
      daily treatments, such as dressing or disinfection, and there were no infections
      or inflammations at the exit site. This study demonstrates that our newly
      developed skin-button system can be useful for preventing infections at the
      driveline exit site.

PMID- 21744125
TI  - Peritoneal dialysis-related infections recommendations: 2010 update. What is new?
AB  - The International Society of Peritoneal Dialysis (ISPD) 2010 guidelines on PD
      related infections reflect the bulk of knowledge acquired over the last 5 years.
      It includes new information about causative agents of peritonitis, isolation
      techniques, or therapeutic regimens. Monitoring of infection rates by reporting
      of peritonitis and exit site infections, isolated microorganism, and presumed
      etiology is recommended. Furthermore, special focus is given on careful
      evaluation of each episode of peritonitis in order to determine the route of
      infection and to reassess patient's training. In this article, we record the
      changes in the last ISPD (2010) guidelines compared to the previous ones
      published in March 2005.

PMID- 21744126
TI  - Primary splenic hydatidosis.
AB  - Primary extrahepatic hydatid cysts are rare, and primary splenic hydatid cysts
      even more so, constituting 2% to 3.5% of all hydatid cysts. We report here a case
      series of isolated splenic hydatid cysts. Case records of 382 adult patients of
      abdominal hydatid cysts were analyzed; eight of them (2%; aged 23 to 45 years, 5
      women and 3 men) had primary splenic hydatid cysts. Seven patients presented with
      dull dragging pain in the left hypochondrium. Four patients had splenomegaly.
      Diagnosis was made at ultrasonography and/or contrast-enhanced computed
      tomography. Enzyme linked immunosorbent assay for hydatid antibodies tested
      positive in all patients. One patient presented with hemoperitoneum. All patients
      underwent splenectomy. Primary splenic hydatid cyst is rare but should be
      considered in patients with cystic lesions of the spleen.

PMID- 21744127
TI  - Unusual presentation of celiac disease presenting with renal complications.
AB  - Celiac disease is a chronic inflammatory condition of small intestine resulting
      due to sensitivity to wheat protein gluten. Most patients in the childhood
      present with primary gastrointestinal complaints. The authors present here two
      young girls with renal complaints later diagnosed to have celiac disease.

PMID- 21744128
TI  - Influence of tidal volume for stroke volume variation to predict fluid
      responsiveness in patients undergoing one-lung ventilation.
AB  - We designed this study to determine the predictive value for fluid responsiveness
      of stroke volume variation (SVV) in patients undergoing one-lung ventilation
      (OLV), ventilated at different tidal volumes. All patients scheduled for
      pulmonary lobectomy were randomized into two groups according to their tidal
      volume [group H: tidal volume 8 ml/kg (n = 36); group L: tidal volume 6 ml/kg (n
      = 37)]. After starting OLV, volume loading was performed by administration of 500
      ml 6% hydroxyethylated starch for 30 min. Hemodynamic variables were measured
      before and after volume loading using the Vigileo-FloTrac system. Patients in
      both groups were divided into fluid responders and non-responders, and responders
      were defined as those who demonstrated an increase in cardiac index >=15% after
      volume expansion. The area under the receiver operating characteristic curve for
      SVV to discriminate between responders and non-responders was 0.776 in group H
      and 0.648 in group L. The optimal threshold value of SVV was 10.5% (sensitivity,
      85.7%; specificity, 66.7%) in group H and 8% (sensitivity, 69.5%; specificity,
      64.3%) in group L. We found that SVV could predict fluid responsiveness in
      patients undergoing OLV with acceptable levels of sensitivity and specificity
      only when tidal volume is at least 8 ml/kg.

PMID- 21744129
TI  - Phenotype-dependent production of des-gamma-carboxy prothrombin in hepatocellular
      carcinoma.
AB  - BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is an established tumor marker
      for hepatocellular carcinoma (HCC), but the precise mechanism of its production
      remains unknown. We have recently demonstrated that cytoskeletal rearrangement
      during the phenotypic changes involved in epithelial mesenchymal transition (EMT)
      plays a crucial role in DCP production through the impairment of vitamin K
      uptake. However, DCP production in long-lasting severe hypoxic conditions with
      nutrient deprivation-such as transarterial embolization-remains unknown. METHODS:
      We examined the effects of long-lasting hypoxia with nutrient deprivation, as
      well as the constitutive expression of hypoxia-inducible factor (HIF)-1alpha, on
      EMT status, DCP production, and protein synthesis in human hepatoma cell lines by
      enzyme-linked immunosorbent assay, immunofluorescent studies, and western
      blotting. Immunohistochemistry findings for DCP, anti-hepatocyte paraffin 1 (Hep
      Par 1), and vimentin were examined using human resected HCC samples. RESULTS:
      Both severe hypoxia with nutrient deprivation and HIF-1alpha transfection led to
      the cessation of DCP production, by attenuating protein synthesis through the
      hypophosphorylation of mammalian target of rapamycin and its effector proteins,
      indicative of a further phenotypic shift involving impaired liver-specific
      protein synthesis. In immunohistochemistry, the distribution of DCP- and Hep Par
      1-positive HCC cells was mostly similar and vimentin-positive HCC cells were
      frequently observed in the areas that were negative for Hep Par 1 and/or DCP.
      CONCLUSIONS: HCC cells produce DCP when they undergo mild phenotypic changes.
      However, when HCC cells adopt mesenchymal properties they lose their capacity for
      protein synthesis, and the production of DCP is attenuated. Building upon our
      previous works, it appears that DCP could be a unique tumor marker that reflects
      the stepwise phenotypic changes of HCC.

PMID- 21744130
TI  - Impairment of protein C secretion in protein C-deficient patients carrying an
      Asp297 mutation.

PMID- 21744131
TI  - Association of obestatin, ghrelin, and inflammatory cytokines in obese patients
      with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Three protein products of ghrelin gene (acylated ghrelin, des
      acylated ghrelin, and obestatin) are involved in appetite stimulation and
      suppression. Additionally, there is some evidence suggesting their involvement in
      metabolic and inflammatory pathways which may be implicated in the pathogenesis
      of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to
      examine the relationships of ghrelin gene products in patients with NAFLD.
      METHODS: We included 75 morbidly obese patients with biopsy-proven NAFLD (41 with
      histologic non-alcoholic steatohepatitis (NASH)) with clinical and laboratory
      data as well as frozen serum samples from the time of liver biopsy. Fasting serum
      was assayed for obestatin as well as acylated and des-acyl-ghrelin concentrations
      using ELISA. Bio-Plex inflammatory cytokine assays were used to profile
      expression of 17 inflammatory mediators, including IL-6, IL-7, IL-8, G-CSF, CCL2,
      and MIP-1beta. RESULTS: Patients with NASH had twofold higher concentration of
      des-acyl-ghrelin than patients with non-NASH (2.58 vs. 1.24 pg/ml, P < 0.02).
      Ghrelin concentrations in NASH patients with fibrosis stage >=2 were almost
      double the concentration of NASH patients with fibrosis stage <2 (8.73 vs. 4.22
      pg/ml, P < 0.04). Obestatin levels also increased with the fibrosis stage (2.54
      vs. 3.46 pg/ml, P < 0.03). NAFLD patients with higher fibrosis stage had lower IL
      7 concentrations (16.89 vs. 10.68 pg/ml, P = 0.014). Obestatin levels at baseline
      significantly correlated with rate of weight loss after bariatric surgery at
      various time points. CONCLUSIONS: This study suggests that products of the GHRL
      gene may be important for the pathogenesis of NASH and fibrosis. Additional
      confirmatory studies are needed.

PMID- 21744132
TI  - Mucosal inflammation in spondylarthritides: past, present, and future.
AB  - Spondylarthritides (SpA) and inflammatory bowel disease (IBD) are idiopathic,
      chronic inflammatory disorders. Although they are very distinct and well-defined
      entities, there is clinical and genetic evidence supporting some degree of
      overlap between the pathogenesis of the two. Subclinical gut inflammation is
      present in up to two thirds of all SpA patients and can evolve into IBD. This
      subclinical gut inflammation has been shown to be strongly associated with joint
      inflammation, providing a clue for a common pathophysiologic background. Despite
      extensive research progress in the field over the past few years, many questions
      remain unanswered. In this paper, we focus on the clinical, genetic, and
      pathophysiologic overlap of SpA and IBD. Furthermore, we discuss some of the
      targets that may influence therapeutic decision making.

PMID- 21744133
TI  - Bacterial cellulose-based materials and medical devices: current state and
      perspectives.
AB  - Bacterial cellulose (BC) is a unique and promising material for use as implants
      and scaffolds in tissue engineering. It is composed of a pure cellulose nanofiber
      mesh spun by bacteria. It is remarkable for its strength and its ability to be
      engineered structurally and chemically at nano-, micro-, and macroscales. Its
      high water content and purity make the material biocompatible for multiple
      medical applications. Its biocompatibility, mechanical strength, chemical and
      morphologic controllability make it a natural choice for use in the body in
      biomedical devices with broader application than has yet been utilized. This
      paper reviews the current state of understanding of bacterial cellulose, known
      methods for controlling its physical and chemical structure (e.g., porosity,
      fiber alignment, etc.), biomedical applications for which it is currently being
      used, or investigated for use, challenges yet to be overcome, and future
      possibilities for BC.

PMID- 21744134
TI  - Effect of different salt adaptation strategies on the microbial diversity,
      activity, and settling of nitrifying sludge in sequencing batch reactors.
AB  - The effect of salinity on the activity of nitrifying bacteria, floc
      characteristics, and microbial community structure accessed by fluorescent in
      situ hybridization and polymerase chain reaction-denaturing gradient gel
      electrophoresis techniques was investigated. Two sequencing batch reactors (SRB1
      and SBR2) treating synthetic wastewater were subjected to increasing salt
      concentrations. In SBR1, four salt concentrations (5, 10, 15, and 20 g NaCl/L)
      were tested, while in SBR2, only two salt concentrations (10 and 20 g NaCl/L)
      were applied in a more shock-wise manner. The two different salt adaptation
      strategies caused different changes in microbial community structure, but did not
      change the nitrification performance, suggesting that regardless of the different
      nitrifying bacterial community present in the reactor, the nitrification process
      can be maintained stable within the salt range tested. Specific ammonium
      oxidation rates were more affected when salt increase was performed more rapidly
      and dropped 50% and 60% at 20 g NaCl/L for SBR1 and SBR2, respectively. A gradual
      increase in NaCl concentration had a positive effect on the settling properties
      (i.e., reduction of sludge volume index), although it caused a higher amount of
      suspended solids in the effluent. Higher organisms (e.g., protozoa, nematodes,
      and rotifers) as well as filamentous bacteria could not withstand the high salt
      concentrations.

PMID- 21744136
TI  - Ultrasound preferred as the immediate preoperative investigation before three-pin
      rigid fixation.

PMID- 21744137
TI  - Severe intra- and periventricular hemorrhage: role of arteriolosclerosis related
      to maternal smoke.
AB  - OBJECTIVE: The authors aimed to describe the atherosclerotic lesions of the
      cerebral arterioles as a substrate of their rupture and bleeding. METHODS: The
      study was performed on the brain of nine Caucasian fetal victims of intra- and
      periventricular hemorrhage, all grade IV, and nine control cases. RESULTS: In the
      nine victims of hemorrhage, the arteriolar wall structure was altered, focally
      transformed into a deposit of amorphous eosinophilic material. Such changes often
      affected the full thickness of the wall causing rupture and hemorrhage. In eight
      of these cases and in two victims of the control group, the mothers were heavy
      cigarette smokers (15-20 cigarettes/day) before and during pregnancy. CONCLUSION:
      The authors conclude that intra- and periventricular hemorrhage can be ascribed
      to the toxic effects of prenatal absorption of nicotine.

PMID- 21744138
TI  - Giant craniocervical schwannoma in a teenage girl.

PMID- 21744139
TI  - Agreement in regard to total sleep time during a nap obtained via a sleep
      polygraph and accelerometer: a comparison of different sensitivity thresholds of
      the accelerometer.
AB  - BACKGROUND: Appropriate sensitivity threshold of accelerometer to measure total
      sleep time during nap is not established. PURPOSE: Actigraphy-derived total sleep
      times during naps were calculated using three different sensitivity threshold
      values and compared with polysomnography. METHOD: The mean age of the 60 subjects
      (53 men and 7 women) was 22.8, ranging from 22 to 27 years. Determination of the
      sleep stage by the polygraph and the sleep/wake judgment by the accelerometer
      obeyed the sleep/wake judgment, and the accelerometer was monitored under
      different sensitivity threshold settings. The study was carried out during one
      afternoon with a 3-h nap opportunity. Kappa statistics, correlations, and several
      indices of accuracy were compared using statistical methods. RESULTS: The mean
      total sleep times during a nap set for 180 min were 160.4, 151.8, and 140.5 min,
      respectively, as judged under the low-sensitive, middle-sensitive, high-sensitive
      settings of an accelerometer worn on the non-dominant wrist. The corresponding
      mean total sleep time as calculated using a sleep polygraph was 133.0 min.
      Sleep/wake judgment by three levels of threshold values for the accelerometer
      showed that high-sensitive threshold showed relatively high specificity (0.452)
      compared with specificities by the low-sensitive threshold (0.249) or by the
      middle-sensitive threshold (0.358). The concordance correlation coefficients and
      95% confidence intervals (in parenthesis) between the total sleep time judged by
      polygraph and low-sensitive, middle-sensitive, or high-sensitive accelerometer
      were 0.40 (0.26-0.51), 0.53 (0.38-0.65), and 0.64 (0.49-0.75), respectively. The
      Bland-Altman plot of the measurements showed higher agreement between the total
      sleep time by polygraph and by the accelerometer using the high-sensitive
      threshold. CONCLUSIONS: From the result obtained in this study, the high
      sensitive accelerometer showed the strongest agreement of total sleep time and
      sleep/wake judgment with the calculated value using the sleep polygraph.

PMID- 21744140
TI  - Spectrum of large copy number variations in 26 diverse Indian populations:
      potential involvement in phenotypic diversity.
AB  - Copy number variations (CNVs) have provided a dynamic aspect to the apparently
      static human genome. We have analyzed CNVs larger than 100 kb in 477 healthy
      individuals from 26 diverse Indian populations of different linguistic, ethnic
      and geographic backgrounds. These CNVRs were identified using the Affymetrix 50K
      Xba 240 Array. We observed 1,425 and 1,337 CNVRs in the deletion and
      amplification sets, respectively, after pooling data from all the populations.
      More than 50% of the genes encompassed entirely in CNVs had both deletions and
      amplifications. There was wide variability across populations not only with
      respect to CNV extent (ranging from 0.04-1.14% of genome under deletion and 0.11
      0.86% under amplification) but also in terms of functional enrichments of
      processes like keratinization, serine proteases and their inhibitors, cadherins,
      homeobox, olfactory receptors etc. These did not correlate with linguistic,
      ethnic, geographic backgrounds and size of populations. Certain processes were
      near exclusive to deletion (serine proteases, keratinization, olfactory
      receptors, GPCRs) or duplication (homeobox, serine protease inhibitors, embryonic
      limb morphogenesis) datasets. Populations having same enriched processes were
      observed to contain genes from different genomic loci. Comparison of polymorphic
      CNVRs (5% or more) with those cataloged in Database of Genomic Variants revealed
      that 78% (2473) of the genes in CNVRs in Indian populations are novel. Validation
      of CNVs using Sequenom MassARRAY revealed extensive heterogeneity in CNV
      boundaries. Exploration of CNV profiles in such diverse populations would provide
      a widely valuable resource for understanding diversity in phenotypes and disease.

PMID- 21744141
TI  - The exudate from an arbuscular mycorrhizal fungus induces nitric oxide
      accumulation in Medicago truncatula roots.
AB  - Nitric oxide (NO) is a signaling molecule involved in plant responses to abiotic
      and biotic stresses. While there is evidence for NO accumulation during legume
      nodulation, almost no information exists for arbuscular mycorrhizas (AM). Here,
      we investigated the occurrence of NO in the early stages of Medicago truncatula
      Gigaspora margarita interaction, focusing on the plant response to fungal
      diffusible molecules. NO was visualized in root organ cultures and seedlings by
      confocal microscopy using the specific probe 4,5-diaminofluorescein diacetate.
      Five-minute treatment with the fungal exudate was sufficient to induce
      significant NO accumulation. The specificity of this response to AM fungi was
      confirmed by the lack of response in the AM nonhost Arabidopsis thaliana and by
      analyzing mutants impaired in mycorrhizal capacities. NO buildup resulted to be
      partially dependent on DMI1, DMI2, and DMI3 functions within the so-called common
      symbiotic signaling pathway which is shared between AM and nodulation.
      Significantly, NO accumulation was not induced by the application of purified Nod
      factor, while lipopolysaccharides from Escherichia coli, known to elicit defense
      related NO production in plants, induced a significantly different response
      pattern. A slight upregulation of a nitrate reductase (NR) gene and the reduction
      of NO accumulation when the enzyme is inhibited by tungstate suggest NR as a
      possible source of NO. Genetic and cellular evidence, therefore, suggests that NO
      accumulation is a novel component in the signaling pathway that leads to AM
      symbiosis.

PMID- 21744142
TI  - Discrepancies between the MRI- and the electrophysiologically defined subthalamic
      nucleus.
AB  - BACKGROUND: The aim of our study was to evaluate discrepancies between the
      electrophysiologically and MRI-defined subthalamic nucleus (STN) in order to
      contribute to the ongoing debate of whether or not microelectrode recording (MER)
      provides additional information to image-guided targeting in deep brain
      stimulation. METHODS: Forty-four STNs in 22 patients with Parkinson's disease
      were investigated. The three-dimensional MRI-defined STN was derived from
      segmentations of axial and coronal T2-weighted images. The electrophysiological
      STNs were generated from intraoperative MERs in 1,487 locations. The
      stereotactical coordinates of positive and negative STN recordings were re
      imported to the planning software, where a three-dimensional reconstruction of
      the electrophysiological STN was performed and fused to the MRI data set. The
      estimated borders of the MRI- and MER-STN were compared. For statistical analysis
      Student's t, Mann-Whitney rank sum and Fisher's exact tests were used. RESULTS:
      MER-STN volumes, which were found outside the MRI-STN, ranged from 0 mm(3) to 87
      mm(3) (mean: 45 mm(3)). A mean of 44% of the MER-STN volumes exceeded the MRI-STN
      (maximum: 85.1%; minimum: 15.1 %); 53.4% (n = 793) of the microelectrode
      recordings were concordant and 46.6% (n = 694) discordant with the MRI-defined
      anatomical STN. Regarding the dorsal borders, we found discrepancies between the
      MER- and MRI-STN of 0.27 mm (= mean; SD: 0.51 mm) on the first operated side and
      1.51 mm (SD: 1.5 mm) on the second (p = 0.010, t-test). CONCLUSIONS: MER provides
      additional information to high-resolution anatomical MR images and may help to
      detect the amount and direction of brain shift.

PMID- 21744143
TI  - Influence of telmisartan on insulin response after glucose loading in obese
      patients with hypertension: ARB trial of hypertension in obese patients with
      hyperinsulinemia assessed by oral glucose tolerance test (ATHLETE).
AB  - INTRODUCTION: The number of patients with both hypertension and obesity has been
      increasing in Japan. Many of these patients may also have insulin resistance.
      Telmisartan, an angiotensin II receptor blocker (ARB), selectively activates
      peroxisome proliferatoractivated receptor (PPAR)-gamma, and this effect is
      considered to markedly improve insulin resistance in obese patients with
      hypertension. We compared the antihypertensive and insulin resistance-improving
      effects of telmisartan with those of candesartan and valsartan in this patient
      population. METHODS: Twenty-eight elderly patients with an average body mass
      index (BMI) of 27.1 kg/m(2) were enrolled in this 6-month study. Patients were
      randomly selected to either switch from candesartan or valsartan to telmisartan
      or to continue with their current ARB. A 75 g oral glucose tolerance test (OGTT)
      was performed before and after switching, and the effect of telmisartan on the
      insulin response to glucose loading was investigated. RESULTS: There was no
      significant difference in blood pressure between the two groups after drug
      administration, but glucose tolerance significantly improved in the telmisartan
      group. The hyperinsulin response to glucose loading also significantly improved
      in those taking telmisartan, as well as homeostasis model assessment of insulin
      resistance (HOMA-IR). These changes were not observed in the control group.
      CONCLUSION: In patients with hypertension and obesity showing insulin resistance,
      treatment with telmisartan significantly improved the hyperinsulin response to
      glucose loading. Telmisartan may therefore be beneficial in these patients.

PMID- 21744144
TI  - The substrate binding cavity of particulate methane monooxygenase from
      Methylosinus trichosporium OB3b expresses high enantioselectivity for n-butane
      and n-pentane oxidation to 2-alcohol.
AB  - The particulate methane monooxygenase (pMMO) of Methylosinus trichosporium OB3b
      oxidized n-butane and n-pentane and mainly produced (R)-2-butanol and (R)-2
      pentanol that comprised 78 and 89% of the product, respectively, indicating that
      the pro-R hydrogen of the 2-position carbon of n-butane and n-pentane is oriented
      toward a catalytic site within the substrate binding site of pMMO. The protein
      cavity adjacent to the catalytic center for pMMO has optimum volume for
      recognizing n-butane and n-pentane for enantioselective hydroxylation.

PMID- 21744145
TI  - Simplified off-gas analyses in animal cell cultures for process monitoring and
      control purposes.
AB  - Batch-to-batch reproducibility of animal cell cultures can significantly be
      enhanced using process control procedures. Most informative signals for advanced
      process control can be derived from the volume fractions of oxygen and carbon
      dioxide in the vent line of the reactors. Here we employed simple low-cost
      sensors, previously not considered for off-gas analysis at a laboratory-scale
      cell cultures, and compared them with a simultaneously used quadrupole mass
      spectrometer, i.e., the standard equipment. A decisive advantage is that the
      sensors did not need any calibration and are easy to use. We show that monitoring
      and advanced control of cell cultures can significantly be simplified using the
      devices tested here and that the same batch-to-batch reproducibility can be
      obtained with much less effort than before.

PMID- 21744146
TI  - Highly regioselective synthesis of undecylenic acid esters of purine nucleosides
      catalyzed by Candida antarctica lipase B.
AB  - Regioselective undecylenoylation of purine nucleosides as potential dual prodrugs
      was achieved by Candida antarctica lipase B using adenosine as a model reactant.
      The optimum organic solvent, molar ratio of vinyl ester to nucleoside, enzyme
      dosage, reaction temperature and molecular sieve amount were anhydrous THF, 5:1,
      20 U/ml, 45 degrees C and 75 mg/ml, respectively. Under the optimum conditions,
      the initial reaction rate, yield and 5'-regioselectivity were 1.1 mM/h, 90% and
      >99%, respectively. The enzymatic acylation of various nucleosides furnished the
      desired 5'-ester derivatives with the yields of 60-95% and 5'-regioselectivities
      of >99%. In addition, the lipase displayed excellent operational stability in
      THF, and retained 96% of its initial activity after reused for five batches.

PMID- 21744147
TI  - Comparison of three microsatellite analysis methods for detecting genetic
      diversity in Phytophthora sojae (Stramenopila: Oomycete).
AB  - Analysis of an organism's genetic diversity requires a method that gives
      reliable, reproducible results. Microsatellites are robust markers, however,
      detection of allele sizes can be difficult with some systems as well as
      consistency among laboratories. In this study, our two laboratories used 219
      isolates of Phytophthora sojae to compare three microsatellite methods. Two
      capillary electrophoresis methods, the Applied Biosystems 3730 Genetic Analyzer
      and the CEQ 8000 Genetic Analysis system, detected an average of 2.4-fold more
      alleles compared to gel electrophoresis with a mean of 8.8 and 3.6 alleles per
      locus using capillary and gel methods, respectively. The two capillary methods
      were comparable, although allele sizes differed consistently by an average of 3.2
      bp across isolates. Differences between capillary methods could be overcome if
      reference standard DNA genotypes are shared between collaborating laboratories.

PMID- 21744148
TI  - Biosynthetic substitution of tyrosine in green fluorescent protein with its
      surrogate fluorotyrosine in Escherichia coli.
AB  - Introduction of a fluorine moiety into green fluorescent protein offers an
      interesting novel spectral variant. The calculated binding energy of
      fluorotyrosine (F-Tyr) (-8.42 kcal/mol) for tyrosyl tRNA synthetase was
      moderately higher than that of tyrosine (Tyr) (-8.36 kcal/mol). This result
      directly correlated with the expression level of F-Tyr containing GFP (38 mg/l),
      which was comparably higher than that of the parent GFP expression level (34
      mg/l). Finally, we generated a model structure for GFP to assess possible
      interaction in the chromophore of the protein structure, which plays an important
      role in determining the spectral and folding behaviors of the F-Tyr incorporated
      GFP variant.

PMID- 21744149
TI  - [Erratum to: Tyrosin kinase inhibitors in oncology.]

PMID- 21744150
TI  - [Innovative antifungals for treatment of invasive fungal infections].
AB  - Invasive fungal infections have gained importance in many areas of clinical
      medicine and represent a growing diagnostic and therapeutic challenge for
      clinicians. During the last decade, several new antifungals were introduced into
      routine therapy: two second-generation triazoles and the new class of
      echinocandins. These innovative drugs showed convincing efficacy and favorable
      safety in randomized clinical trials. Consequently, they were integrated in
      recent therapeutic guidelines, often replacing former standard drugs as first
      line options. The echinocandins (anidulafungin, caspofungin, micafungin)
      primarily have gained a central role in the treatment of invasive Candida
      infections, while the novel triazoles voriconazole and posaconazole established
      themselves as the current mainstays in therapy and prophylaxis of invasive fungal
      infections, particularly aspergillosis, in hemato-oncologic high-risk patients.

PMID- 21744151
TI  - The diagnostic value of intracoronary optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a novel light-based imaging modality for
      application in the coronary circulation. Compared to conventional intravascular
      ultrasound, OCT has a ten-fold higher image resolution. This advantage has seen
      OCT successfully applied in the assessment of atherosclerotic plaque, stent
      apposition, and tissue coverage, heralding a new era in intravascular coronary
      imaging. The present article discusses the diagnostic value of OCT, both in
      cardiovascular research as well as in potential clinical application.The
      unparalleled high image resolution and strong contrast between the coronary lumen
      and the vessel wall structure enable fast and reliable image interpretation. OCT
      makes it possible to visualize the presence of atherosclerotic plaque in order to
      characterize the structure and extent of coronary plaque and to quantify lumen
      dimensions, as well as the extent of lumen narrowing, in unprecedented detail.
      Based on optical properties, OCT is able to distinguish different tissue types,
      such as fibrous, lipid-rich, necrotic, or calcified tissue. Furthermore, OCT is
      able to cover the visualization of a variety of features of atherosclerotic
      plaques that have been associated with rapid lesion progression and clinical
      events, such as thin cap fibroatheroma, fibrous cap thickness, dense macrophage
      infiltration, and thrombus formation. These unique features allow the use of OCT
      to assess patients with acute coronary syndrome and to study the dynamic nature
      of coronary atherosclerosis in vivo and over time. This permits new insights into
      plaque progression, regression, and rupture, as well as the study of effects of
      therapies aimed at modulating these developments.Today's OCT technology allows
      high detail resolution as well as fast and safe clinical image acquisition. These
      unique features have established OCT as the gold standard for the assessment of
      coronary stents. This technique makes it possible to study stent expansion, peri
      procedural vessel trauma, and the interaction of the stent with the vessel wall
      down to the level of individual stent struts, both acutely as well as in the long
      term, where it is has proven extremely sensitive to the detection of even minor
      amounts of tissue coverage. These qualities render OCT indispensable to
      addressing vexing clinical questions such as the relationship of drug-eluting
      stent deployment, vascular healing, the true time course of endothelial stent
      coverage, and late stent thrombosis. This may also better guide the optimal
      duration of dual anti-platelet therapy that currently remains unclear and
      relatively empirical.In the future, OCT might emerge, parallel to its undisputed
      position in research, as the tool of choice in all clinical scenarios where
      angiography is limited by its nature as a two-dimensional luminogram.

PMID- 21744152
TI  - Integrating landscape ecology and geoinformatics to decipher landscape dynamics
      for regional planning.
AB  - We used remote sensing and GIS in conjunction with multivariate statistical
      methods to: (i) quantify landscape composition (land cover types) and
      configuration (patch density, diversity, fractal dimension, contagion) for five
      coastal watersheds of Kalloni gulf, Lesvos Island, Greece, in 1945, 1960, 1971,
      1990 and 2002/2003, (ii) evaluate the relative importance of physical (slope,
      geologic substrate, stream order) and human (road network, population density)
      variables on landscape composition and configuration, and (iii) characterize
      processes that led to land cover changes through land cover transitions between
      these five successive periods in time. Distributions of land cover types did not
      differ among the five time periods at the five watersheds studied because the
      largest cumulative changes between 1945 and 2002/2003 did not take place at
      dominant land cover types. Landscape composition related primarily to the
      physical attributes of the landscape. Nevertheless, increase in population
      density and the road network were found to increase heterogeneity of the
      landscape mosaic (patchiness), complexity of patch shape (fractal dimension), and
      patch disaggregation (contagion). Increase in road network was also found to
      increase landscape diversity due to the creation of new patches. The main
      processes involved in land cover changes were plough-land abandonment and
      ecological succession. Landscape dynamics during the last 50 years corroborate
      the ecotouristic-agrotouristic model for regional development to reverse trends
      in agricultural land abandonment and human population decline and when combined
      with hypothetical regulatory approaches could predict how this landscape could
      develop in the future, thus, providing a valuable tool to regional planning.

PMID- 21744153
TI  - Liver histology as predictor of outcome in patients with acute-on-chronic liver
      failure (ACLF).
AB  - There is paucity of literature on liver histological spectrum of acute-on-chronic
      liver failure (ACLF). The aims of this study are to (a) to characterize the liver
      histological features in ACLF, (b) to correlate histological parameters with
      prognosis, and (c) to investigate whether etiology influences prognosis. We
      retrospectively studied liver biopsies of patients with ACLF. The histological
      findings were correlated with the clinical outcome. Fifty cases (median age, 39
      years [10-69 years]; M/F, 3:1) were included. Etiology of acute insult was viral
      or alcohol in majority of the cases. Twenty-five patients survived (good outcome,
      50%) and 25 died (poor outcome, 50%). On a univariate analysis, the outcome
      correlated with fibrosis, ballooning, eosinophilic degeneration, ductular
      proliferation, pericellular fibrosis, Mallory's hyaline, foci of confluent
      necrosis and/or bridging necrosis (CN/BN), cholestasis, apoptosis (present), and
      parenchyma left. However, on a multivariate analysis, only fibrosis, ballooning,
      ductular proliferation, apoptosis, and parenchyma left were found to be
      independently associated with outcome. Two distinct patterns of liver histology
      were observed: pattern I, observed in cases with poor outcome, showing marked
      ductular proliferation, coarse inspissated ductular bile plugs, eosinophilic
      degeneration of hepatocytes, foci of CN/BN, higher apoptosis, pericellular
      fibrosis, Mallory's hyaline, and higher stage of fibrosis. Pattern II is seen in
      cases with good outcome, show prominent hepatocyte ballooning with lesser
      parenchymal involvement by fibrosis and necrosis. Histological features of liver
      biopsy are: extent of fibrosis, ballooning, ductular proliferation, apoptosis,
      and lesser degree of parenchymal replacement by fibrosis or necrosis which
      correlates with the outcome in patients with ACLF. Two distinct patterns of liver
      histology are seen which help in prognostication.

PMID- 21744154
TI  - In silico identification of new ligands for GPR17: a promising therapeutic target
      for neurodegenerative diseases.
AB  - GPR17, a previously orphan receptor responding to both uracil nucleotides and
      cysteinyl-leukotrienes, has been proposed as a novel promising target for human
      neurodegenerative diseases. Here, in order to specifically identify novel potent
      ligands of GPR17, we first modeled in silico the receptor by using a multiple
      template approach, in which extracellular loops of the receptor, quite complex to
      treat, were modeled making reference to the most similar parts of all the class-A
      GPCRs crystallized so far. A high-throughput virtual screening exploration of
      GPR17 binding site with more than 130,000 lead-like compounds was then applied,
      followed by the wet functional and pharmacological validation of the top-scoring
      chemical structures. This approach revealed successful for the proposed aim, and
      allowed us to identify five agonists or partial agonists with very diverse
      chemical structure. None of these compounds could have been expected 'a priori'
      to act on a GPCR, and all of them behaved as much more potent ligands than GPR17
      endogenous activators.

PMID- 21744155
TI  - New developments in brief interventions to treat problem drinking in nonspecialty
      health care settings.
AB  - The delivery of brief interventions (BIs) in health care settings to reduce
      problematic alcohol consumption is a key preventive strategy for public health.
      However, evidence of effectiveness beyond primary care is inconsistent. Patient
      populations and intervention components are heterogeneous. Also, evidence for
      successful implementation strategies is limited. In this article, recent
      literature is reviewed covering BI effectiveness for patient populations and
      subgroups, and design and implementation of BIs. Support is evident for short
      term effectiveness in hospital settings, but long-term effects may be confounded
      by changes in control groups. Limited evidence suggests effectiveness with young
      patients not admitted as a consequence of alcohol, dependent patients, and binge
      drinkers. Influential BI components include high-quality change plans and
      provider characteristics. Health professionals endorse BI and feel confident in
      delivering it, but training and support initiatives continue to show no
      significant effects on uptake, prompting calls for systematic approaches to
      implementing BI in health care.

PMID- 21744156
TI  - Catheter-based ablation for ventricular arrhythmias.
AB  - Catheter ablation for patients with recurrent ventricular arrhythmias has emerged
      as an important and effective treatment option. The approach to ablation, and the
      risks and likely efficacy are determined by the nature of the severity and type
      of underlying heart disease. Although implantable defibrillators remain the
      corner stone for prevention of sudden cardiac death, ablation successfully
      reduces tachycardia recurrences and storms of ventricular arrhythmias triggering
      defibrillator shocks in patients with structural heart disease. Our understanding
      of idiopathic ventricular tachycardia (VT) has grown substantially with several
      new sites of VT origin recognized in recent years. Ablation is often curative for
      idiopathic VT. This review discusses common mechanisms and clues to diagnosis of
      the various VTs, and current advances in ablation options. In particular,
      endocardial ablation techniques have been complemented by newer approaches such
      as percutaneous epicardial ablation. In rare cases, transcoronary alcohol
      ablation can be effective for life-threatening arrhythmia.

PMID- 21744157
TI  - Update on the management of atrial fibrillation: anticoagulation and medical
      therapy.
AB  - 2010 saw the introduction of dabigatran (Pradaxa; Boehringer Ingelheim
      Pharmaceuticals, Ridgefield, CT), following US Food and Drug Administration
      approval, into daily clinical practice in the United States as an alternative to
      Coumadin (Bristol-Myers-Squibb, New York, NY) therapy. Dronedarone (Multaq;
      Sanofi-Aventis, Bridgewater, NJ), originally approved for use in the United
      States in 2009, has seen further widespread deployment in contemporary clinical
      practice. Intravenous vernakalant (Cardiome Pharm, Vancouver, B.C., Canada; Merck
      & Co., Whitehouse Station, NJ) is being considered for approval in the United
      States and may serve as an alternative to current agents for safe and efficacious
      acute conversion from atrial fibrillation. We focus primarily on new information
      concerning these and other antiarrhythmic drug and anticoagulation therapies. We
      provide brief updates of recently published articles along with our perspective
      on how they will likely alter clinical practice now and in the future.

PMID- 21744158
TI  - Biodegradation of methyl parathion and p-nitrophenol by a newly isolated
      Agrobacterium sp. strain Yw12.
AB  - Strain Yw12, isolated from activated sludge, could completely degrade and utilize
      methyl parathion as the sole carbon, phosphorus and energy sources for growth in
      the basic salt media. It could also completely degrade and utilize p-nitrophenol
      as the sole carbon and energy sources for growth in the minimal salt media.
      Phenotypic features, physiological and biochemical characteristics, and
      phylogenetic analysis of 16S rRNA sequence showed that this strain belongs to the
      genus of Agrobacterium sp. Response surface methodology was used to optimize
      degradation conditions. Under its optimal degradation conditions, 50 mg l(-1) MP
      was completely degraded within 2 h by strain Yw12 and the degradation product PNP
      was also completely degraded within 6 h. Furthermore, strain Yw12 could also
      degrade phoxim, methamidophos, chlorpyrifos, carbofuran, deltamethrin and
      atrazine when provided as the sole carbon and energy sources. Enzymatic analysis
      revealed that the MP degrading enzyme of strain Yw12 is an intracellular enzyme
      and is expressed constitutively. These results indicated that strain Yw12 might
      be used as a potential and effective organophosphate pesticides degrader for
      bioremediation of contaminated sites.

PMID- 21744159
TI  - Autoregulatory properties of (+)-thujopsene and influence of environmental
      conditions on its production by Penicillium decumbens.
AB  - A Penicillium decumbens strain was collected from a water-damaged building, and
      the production of microbial volatile organic compounds (MVOCs) was investigated
      by means of headspace solid-phase microextraction, followed by GC-MS analysis.
      The strain was characterized by a high production of (+)-thujopsene. The
      influence of various temperatures, relative humidity (RH) values, substrates, and
      inoculum concentrations on fungal growth and (+)-thujopsene production was
      studied. The optimal temperature and relative humidity for P. decumbens growth
      were 30 degrees C and 100% RH, respectively. In general, the more favourable the
      incubation parameters were for growth, the faster maximum (+)-thujopsene
      production was reached. Moreover, the antifungal activity of thujopsene was
      tested against 16 fungal strains. The growth of five of these fungal strains was
      negatively affected both by thujopsene alone and when grown in contact with the
      MVOCs produced by P. decumbens. Following these results and since growth of P.
      decumbens itself was also inhibited by thujopsene, an autoregulatory function for
      this compound was proposed. Few data are present in the literature about chemical
      communication between fungi. The present research could, therefore, contribute to
      understanding fungal metabolism and behaviour in indoor environments.

PMID- 21744160
TI  - Who is counseled to lose weight? Survey results and anthropometric data from
      3,149 lower socioeconomic women.
AB  - Because obesity is a grave public health concern, this study examined the
      percentage of disadvantaged women who recalled ever having received weight loss
      advice from a healthcare provider and factors associated with such advice. This
      study was part of a 5-clinic, cervical cancer prevention trial. Patients not
      immediately post-partum completed a Spanish/English survey; height and weight
      were also obtained. Of the 3,149 respondents (response rate 83%), 2,138 (68%)
      were overweight or obese (body mass index (BMI) >= 25); 94% reported a household
      income of <$35,000/year; 69% were Hispanic; 10% non-Hispanic black; and 40%
      completed the survey in Spanish. Only one-third reported ever having been told to
      lose weight. Based on BMI, these rates were 15% in the 25-29.9 range
      (overweight); 34% within 30-34.9; 57% within 35-39.9; and 73% >= 40. In
      univariate analyses, among overweight women, diabetes or English-speaking was
      associated with weight loss advice. In multivariate analyses, being older, more
      educated, and diabetic were associated with such advice. 48% of non-Hispanic
      whites, 31% of non-Hispanic blacks, and 29% of Hispanic had a home scale. Among
      disadvantaged women, obesity alone does not determine who recalls weight loss
      advice. Language barriers and lack of a home scale merit further study to address
      obesity.

PMID- 21744161
TI  - [Treatment of metastatic bone disease and treatment-induced osteoporosis in
      prostate cancer. Evolution of osteoprotective strategies].
AB  - Patients with prostate cancer and bone metastases on average experience one
      skeletal-related event per year. To avoid complications caused by bone metastases
      and androgen deprivation therapy-induced osteoporosis, which lead to significant
      increases in costs and mortality, bone metabolism can be influenced in several
      ways. Bisphosphonates, which directly inhibit signalling pathways in osteoclasts,
      can reduce the rate of skeletal-related events in metastatic prostate cancer. The
      RANKL antibody denosumab inhibits the crosstalk between osteoblasts, osteoclasts
      and tumour cells and has been shown to reduce the rate of vertebral fractures in
      patients with treatment-induced osteoporosis. Furthermore, it has been recently
      shown to prevent skeletal-related events in prostate cancer patients with
      metastatic bone disease. In patients with castration resistant prostate cancer,
      denosumab prolongs bone-metastasis-free-survival. Whereas ample data are
      available about side effects of bisphosphonates, limited evidence exists about
      the long-term safety profile of denosumab. Therefore, a thorough patient
      selection is advocated for therapeutic application of denosumab in patients with
      prostate cancer.

PMID- 21744162
TI  - Mycorrhizal colonization does not affect tolerance to defoliation of an annual
      herb in different light availability and soil fertility treatments but increases
      flower size in light-rich environments.
AB  - Heterogeneous distribution of resources in most plant populations results in a
      mosaic of plant physiological responses tending to maximize plant fitness. This
      includes plant responses to trophic interactions such as herbivory and
      mycorrhizal symbiosis which are concurrent in most plants. We explored fitness
      costs of 50% manual defoliation and mycorrhizal inoculation in Datura stramonium
      at different light availability and soil fertility environments in a greenhouse
      experiment. Overall, we showed that non-inoculated and mycorrhiza-inoculated
      plants did not suffer from 50% manual defoliation in all the tested combinations
      of light availability and soil fertility treatments, while soil nutrients and
      light availability predominately affected plant responses to the mycorrhizal
      inoculation. Fifty percent defoliation had a direct negative effect on
      reproductive traits whereas mycorrhiza-inoculated plants produced larger flowers
      than non-inoculated plants when light was not a limiting factor. Although D.
      stramonium is a facultative selfing species, other investigations had shown clear
      advantages of cross-pollination in this species; therefore, the effects of
      mycorrhizal inoculation on flower size observed in this study open new lines of
      inquiry for our understanding of plant responses to trophic interactions. Also in
      this study, we detected shifts in the limiting resources affecting plant
      responses to trophic interactions.

PMID- 21744163
TI  - Leaf hydraulic vulnerability influences species' bioclimatic limits in a diverse
      group of woody angiosperms.
AB  - The ability of plants to maintain water flow through leaves under water stress
      induced tension (assessed as the leaf hydraulic vulnerability; P50(leaf)) is
      intimately linked with survival. We examined the significance of P50(leaf) as an
      adaptive trait in influencing the dry-end distributional limits of cool temperate
      woody angiosperm species. We also examined differences in within-site variability
      in P50(leaf) between two high-rainfall montane rainforest sites in Tasmania and
      Peru, respectively. A significant relationship between P50(leaf) and the 5th
      percentile of mean annual rainfall across each species distribution was found in
      Tasmania, suggesting that P50(leaf) influences species climatic limits.
      Furthermore, a strong correlation between P50(leaf) and the minimum rainfall
      availability was found using five phylogenetically independent species pairs in
      wet and dry evergreen tree species, suggesting that rainfall is an important
      selective agent in the evolution of leaf hydraulic vulnerability. Greater within
      site variability in P50(leaf) was found among dominant montane rainforest species
      in Tasmania than in Peru and this result is discussed within the context of
      differences in spatial and temporal environmental heterogeneity and parochial
      historical ecology.

PMID- 21744164
TI  - Progress in HDL-based therapies for atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease affecting medium and large
      arteries resulting from a complex interaction between genetic and environmental
      risk factors that include dyslipidemia, hypertension, diabetes mellitus, and
      smoking. The most serious manifestations of atherosclerotic vascular disease,
      such as unstable angina, myocardial infarction, ischemic stroke, and sudden
      death, largely result from thrombosis superimposed on a disrupted (ruptured or
      eroded) atherosclerotic plaque. Adoption and maintenance of a healthy lifestyle
      coupled with management of modifiable risk factors significantly reduce the
      adverse clinical consequences of athero-thrombosis. Reducing low-density
      lipoprotein cholesterol levels using statins and other agents serves as the
      primary pharmacologic approach to stabilize atherosclerotic vascular disease.
      However, a large residual risk remains, prompting the search for additional
      therapies for atherosclerosis management, such as raising atheroprotective high
      density lipoprotein (HDL) and/or improving HDL function. This review focuses on
      new and emerging HDL-based therapeutic strategies targeting atherosclerosis.

PMID- 21744165
TI  - Solid-state NMR sequential assignments of alpha-synuclein.
AB  - Parkinson's disease is amongst the most frequent and most devastating
      neurodegenerative diseases. It is tightly associated with the assembly of
      proteins into high-molecular weight protein species, which propagate between
      neurons in the central nervous system. The principal protein involved in this
      process is alpha-synuclein which is a structural component of the Lewy bodies
      observed in diseased brain. We here present the solid-state NMR sequential
      assignments of a new fibrillar form of this protein, the first one with a well
      ordered and rigid N-terminal part.

PMID- 21744166
TI  - Short-term and mid-term control of type 2 diabetes mellitus by laparoscopic
      sleeve gastrectomy with ileal interposition.
AB  - BACKGROUND: Standard surgical procedures used for the treatment of morbid obesity
      constitute optional treatments for type 2 diabetes mellitus (T2DM). The aim of
      the present study was to evaluate the short- and mid-term effects of laparoscopic
      sleeve gastrectomy (SG) with ileal interposition (II) in T2DM patients (n = 30).
      METHODS: The variables investigated were the feasibility of the procedure,
      remission/alleviation of the disease, morbidity, mortality, and weight loss.
      Patients were followed during a period of 6-18 months after surgery. RESULTS: The
      average time required for the surgical procedure was 181.47 +/- 53.23 min, and
      the mean duration of postoperative hospital stay was 3.17 +/- 0.79 days. There
      were no intraoperative complications, and none of the patients required
      conversion to open surgery. Postoperatively, all patients experienced a
      significant weight loss: i.e., the mean body mass index (BMI) values prior to and
      following surgery were significantly different (P = 0.0001). Postoperative levels
      of glycosylated hemoglobin, fasting glucose, and fructosamine were significantly
      reduced (P = 0.0001, 0.0001, and 0.0004, respectively) from those detected prior
      to surgery. Remission of T2DM was observed in 80% of the patients over the follow
      up period, and these subjects no longer required treatment with hypoglycemic
      drugs or diet. The remaining 20% of patients presented significant improvement in
      their condition but needed an oral hypoglycemic medication. CONCLUSIONS: Adequate
      glycemic control, adjustable weight loss, and absence of nutritional deficiencies
      were the main benefits offered by the surgical intervention. The results indicate
      that SG/II treatment could be a promising alternative for patients with T2DM.

PMID- 21744167
TI  - Gene profiling in ductus arteriosus and aorta: a question of consistency.

PMID- 21744168
TI  - The stabilizing effect of moisture on the solid-state degradation of gabapentin.
AB  - Gabapentin is known to undergo intramolecular cyclization to form a lactam (gaba
      L) with concomitant loss of water. Gabapentin was milled in a planetary mill for
      15-60 min. Unmilled and milled gabapentin were stored at 50 degrees C with
      relative humidity ranged between 5% and 90%. The unmilled and milled samples were
      assayed for gabapentin and gaba-L by reversed phase-high-performance liquid
      chromatography and also subjected to powder X-ray diffraction, solid-state
      nuclear magnetic resonance and surface area analyses. The rates of lactamization
      in the milled gabapentin samples correlated to increased surface area, milling
      duration, and in-process lactam levels. This effect of milling could not be
      explained solely by the increase in surface area with increased milling time but
      was more likely due to increased regions of crystal disorder caused by the
      mechanical and thermal milling stresses. The lactamization rate of milled
      gabapentin samples was greatest in the presence of the lowest humidity conditions
      and dramatically decreased with increasing humidity. In particular, milled
      gabapentin appeared to be much more stable at humidity levels greater than 31%
      RH. This finding could not be attributed to the possibility of lactam hydrolysis
      at high humidity but rather to a competitive annealing process wherein milling
      induced crystal defects were lost upon exposure to atmospheric moisture thereby
      stabilizing the milling-damaged drug substance.

PMID- 21744169
TI  - Correlation of the Ga-68-bombesin analog Ga-68-BZH3 with receptors expression in
      gliomas as measured by quantitative dynamic positron emission tomography (dPET)
      and gene arrays.
AB  - PURPOSE: The kinetics of Ga-68-BZH3, a Ga-68-bombesin analog, was compared to
      molecular biological data obtained from gene arrays in seven patients with a
      recurrent glioma. The primary aim of this study was the correlation of receptor
      expression and tracer kinetics. PROCEDURES: Dynamic positron emission tomography
      studies were performed and the data were analyzed by a volume-of-interest
      technique using a two-tissue compartment model as well as a non-compartment
      model. Gene array data were obtained from gene array analysis of tumor tissue
      samples. RESULTS: The correlation analysis revealed a significant nonlinear
      correlation of r = 0.89 (p < 0.03) for k1 and BB(2) (gastrin-releasing peptide
      receptor). BB(1) and BB(3) were not significantly correlated with k1. vb and k3
      were not significantly correlated with the expression data of the receptors on
      the p < 0.05 level. CONCLUSIONS: The parameter k1 is correlated with the
      expression of BB(2) based on gene array data. The quantitative analysis of the Ga
      68-BZH3 kinetics can be used to predict the receptor expression of BB(2) in
      gliomas based on k1 of the compartment analysis. However, this study is limited
      to the expression data on the mRNA level and further studies are needed to assess
      the correlation of gene expression on the protein level.

PMID- 21744170
TI  - Coronary artery involvement in cardiac amyloidosis.

PMID- 21744171
TI  - Immunogenicity of therapeutic proteins: the use of animal models.
AB  - Immunogenicity of therapeutic proteins lowers patient well-being and drastically
      increases therapeutic costs. Preventing immunogenicity is an important issue to
      consider when developing novel therapeutic proteins and applying them in the
      clinic. Animal models are increasingly used to study immunogenicity of
      therapeutic proteins. They are employed as predictive tools to assess different
      aspects of immunogenicity during drug development and have become vital in
      studying the mechanisms underlying immunogenicity of therapeutic proteins.
      However, the use of animal models needs critical evaluation. Because of species
      differences, predictive value of such models is limited, and mechanistic studies
      can be restricted. This review addresses the suitability of animal models for
      immunogenicity prediction and summarizes the insights in immunogenicity that they
      have given so far.

PMID- 21744172
TI  - Investigation of solid phase composition on tablet surfaces by grazing incidence
      X-ray diffraction.
AB  - PURPOSE: To investigate solid state transformations of drug substances during
      compaction using grazing incidence X-ray diffraction (GIXD). METHODS: The solid
      forms of three model drugs-theophylline (TP), nitrofurantoin (NF) and amlodipine
      besylate (AMB)-were compacted at different pressures (from 100 to 1000 MPa);
      prepared tablets were measured using GIXD. After the initial measurements of
      freshly compacted tablets, tablets were subjected to suitable recrystallization
      treatment, and analogous measurements were performed. RESULTS: Solid forms of TP,
      NF and AMB showed partial amorphization as well as crystal disordering during
      compaction; the extent of these effects generally increased as a function of
      pressure. The changes were most pronounced at the outer surface region. The
      different solid forms showed difference in the formation of amorphicity/crystal
      disordering. Dehydration due to compaction was observed for the TP monohydrate,
      whereas hydrates of NF and AMB were stable towards dehydration. CONCLUSIONS: With
      GIXD measurements, it was possible to probe the solid form composition at the
      different depths of the tablet surfaces and to obtain depth-dependent information
      on the compaction-induced amorphization, crystal disordering and dehydration.

PMID- 21744173
TI  - Controlled release of octreotide and assessment of peptide acylation from
      poly(D,L-lactide-co-hydroxymethyl glycolide) compared to PLGA microspheres.
AB  - PURPOSE: To investigate the in vitro release of octreotide acetate, a
      somatostatin agonist, from microspheres based on a hydrophilic polyester,
      poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA). METHODS: Spherical and non
      porous octreotide-loaded PLHMGA microspheres (12 to 16 MUm) and loading
      efficiency of 60-70% were prepared by a solvent evaporation. Octreotide release
      profiles were compared with commercial PLGA formulation (Sandostatin LAR((r)));
      possible peptide modification with lactic, glycolic and hydroxymethyl glycolic
      acid units was monitored. RESULTS: PLHMGA microspheres showed burst release
      (~20%) followed by sustained release for 20-60 days, depending on the
      hydrophilicity of the polymer. Percentage of released loaded peptide was high (70
      90%); > 60% of released peptide was native octreotide. PLGA microspheres did not
      show peptide release for the first 10 days, after which it was released in a
      sustained manner over the next 90 days; > 75% of released peptides were acylated
      adducts. CONCLUSIONS: PLHMGA microspheres are promising controlled systems for
      peptides with excellent control over release kinetics. Moreover, substantially
      less peptide modification occurred in PLHMGA than in PLGA microspheres.

PMID- 21744174
TI  - Opsonization, biodistribution, cellular uptake and apoptosis study of PEGylated
      PBCA nanoparticle as potential drug delivery carrier.
AB  - PURPOSE: For nanocarrier-based targeted delivery systems, preventing phagocytosis
      for prolong circulation half life is a crucial task. PEGylated poly(n-butylcyano
      acrylate) (PBCA) NP has proven a promising approach for drug delivery, but an
      easy and reliable method of PEGylation of PBCA has faced a major bottleneck.
      METHODS: PEGylated PBCA NPs containing docetaxel (DTX) by modified anionic
      polymerization reaction in aqueous acidic media containing amine functional PEG
      were made as an single step PEGylation method. In vitro colloidal stability
      studies using salt aggregation method and antiopsonization property of prepared
      NPs using mouse macrophage cell line RAW264 were performed. In vitro performance
      of anticancer activity of prepared formulations was checked on MCF7 cell line.
      NPs were radiolabeled with 99mTc and intravenously administered to study blood
      clearance and biodistribution in mice model. RESULTS: These formulations very
      effectively prevented phagocytosis and found excellent carrier for drug delivery
      purpose. In vivo studies display long circulation half life of PBCA-PEG20 NP in
      comparison to other formulations tested. CONCLUSIONS: The PEGylated PBCA
      formulation can work as a novel tool for drug delivery which can prevent RES
      uptake and prolong circulation half life.

PMID- 21744175
TI  - Multistationarity in mass action networks with applications to ERK activation.
AB  - Ordinary Differential Equations (ODEs) are an important tool in many areas of
      Quantitative Biology. For many ODE systems multistationarity (i.e. the existence
      of at least two positive steady states) is a desired feature. In general
      establishing multistationarity is a difficult task as realistic biological models
      are large in terms of states and (unknown) parameters and in most cases poorly
      parameterized (because of noisy measurement data of few components, a very small
      number of data points and only a limited number of repetitions). For mass action
      networks establishing multistationarity hence is equivalent to establishing the
      existence of at least two positive solutions of a large polynomial system with
      unknown coefficients. For mass action networks with certain structural
      properties, expressed in terms of the stoichiometric matrix and the reaction rate
      exponent matrix, we present necessary and sufficient conditions for
      multistationarity that take the form of linear inequality systems. Solutions of
      these inequality systems define pairs of steady states and parameter values. We
      also present a sufficient condition to identify networks where the aforementioned
      conditions hold. To show the applicability of our results we analyse an ODE
      system that is defined by the mass action network describing the extracellular
      signal-regulated kinase (ERK) cascade (i.e. ERK-activation).

PMID- 21744176
TI  - Colonic strangulation and perforation in traumatic abdominal hernia: unusual
      emergency treatment for a rare trauma complication.
AB  - Traumatic abdominal wall hernia (TAWH) is a muscle-fascial rupture due to a blunt
      direct or indirect trauma. High energy trauma is the principal cause of TAWH and
      they are consequence of car accidents in 50-70% and motorcycle in 15-20%. Similar
      trauma is described even in infant age following bicycle handlebar trauma
      (handlebar injuries). Surgical treatment can be urgent or secondary according to
      the lesions of the patient. Visceral complications secondary to TAWH are
      extremely rare and they are difficult to treat.

PMID- 21744177
TI  - On the limits of top-down control of visual selection.
AB  - In the present study, observers viewed displays in which two equally salient
      color singletons were simultaneously present. Before each trial, observers
      received a word cue (e.g., the word red, or green) or a symbolic cue (a circle
      colored red or green) telling them which color singleton to select on the
      upcoming trial. Even though many theories of visual search predict that observers
      should be able to selectively attend the target color singleton, the results of
      the present study show that observers could not select the target singleton
      without interference from the irrelevant color singleton. The results indicate
      that the irrelevant color singleton captured attention. Only when the color of
      the target singleton remained the same from one trial to the next was selection
      perfect--an effect that is thought to be the result of passive automatic
      intertrial priming. The results of the present study demonstrate the limits of
      top-down attentional control.

PMID- 21744178
TI  - [Consequences of the German federal Guardianship Law after reunification (1992
      2009)].
AB  - BACKGROUND: The Guardianship Law became effective in the year 1992 with the
      intention of replacing the paternalistic-restrictive model by a model based on
      the principles of participation and empowerment. METHODS: Data from the Federal
      Ministry of Justice were used to examine the development of 12 legal guardianship
      parameters over a period of 17 years (1992-2009) at the level of federal states.
      Due to the completely different practise in both parts of Germany before
      reunification, the development will be analysed separately for the old and the
      new federal states. RESULTS: All examined parameters indicate an increase of
      legal guardianship. The highest increases were found for enlargement of the task
      scope (+606%) and for approval of contention measures (+868%). With the exception
      of involuntary commitment rates, in the new federal states the mean values of all
      variables score higher than in the old federal states. Legal guardianship
      installation only increased for the old federal states significantly (T(9)=6.64;
      p=0.007); however, the guardianship expenses were higher, but not significantly,
      for the new federal states. DISCUSSION: In spite of the legal changes in the
      direction of a dynamic instrument in mental health care, the practise of the
      Legal Guardianship Law indicates a continuous increase of guardianship orders
      since 1992. It is necessary to recognise that a slowdown of the upward trend is
      not in sight. Therefore it is pertinent to call those persons in charge of
      regulating legal guardianship to consider their daily practise carefully. On the
      other hand it is a task of mental health services research to analyse the driving
      factors of the presented developments.

PMID- 21744179
TI  - The orientation of swimming biflagellates in shear flows.
AB  - Biflagellated algae swim in mean directions that are governed by their
      environments. For example, many algae can swim upward on average (gravitaxis) and
      toward downwelling fluid (gyrotaxis) via a variety of mechanisms. Accumulations
      of cells within the fluid can induce hydrodynamic instabilities leading to
      patterns and flow, termed bioconvection, which may be of particular relevance to
      algal bioreactors and plankton dynamics. Furthermore, knowledge of the behavior
      of an individual swimming cell subject to imposed flow is prerequisite to a full
      understanding of the scaled-up bulk behavior and population dynamics of cells in
      oceans and lakes; swimming behavior and patchiness will impact opportunities for
      interactions, which are at the heart of population models. Hence, better
      estimates of population level parameters necessitate a detailed understanding of
      cell swimming bias. Using the method of regularized Stokeslets, numerical
      computations are developed to investigate the swimming behavior of and fluid flow
      around gyrotactic prolate spheroidal biflagellates with five distinct flagellar
      beats. In particular, we explore cell reorientation mechanisms associated with
      bottom-heaviness and sedimentation and find that they are commensurate and
      complementary. Furthermore, using an experimentally measured flagellar beat for
      Chlamydomonas reinhardtii, we reveal that the effective cell eccentricity of the
      swimming cell is much smaller than for the inanimate body alone, suggesting that
      the cells may be modeled satisfactorily as self-propelled spheres. Finally, we
      propose a method to estimate the effective cell eccentricity of any biflagellate
      when flagellar beat images are obtained haphazardly.

PMID- 21744180
TI  - The availability of integrated care in a national sample of therapeutic
      communities.
AB  - Therapeutic communities (TCs) for substance abusers are oriented toward changing
      the entire person as a means for facilitating a drug-free future. This vision
      parallels ideas such as integrated care for the treatment of co-occurring
      substance abuse and psychiatric conditions. The extent to which integrated
      services are available in TCs has not been documented. Using data from a national
      sample of 345 TCs, this paper examines the availability of integrated care in TCs
      and the structural and cultural characteristics of TCs that offer integrated
      care. The results indicate that a substantial portion of TCs in this sample admit
      clients with co-occurring disorders (70.7%), and as many as half of the TCs offer
      integrated care. TCs that offer integrated care show increased use of
      professional staff, individual psychotherapy, and a less confrontational milieu,
      but notably, retain many of the "essential elements" of the traditional TC model.

PMID- 21744181
TI  - Rituximab in refractory Vogt-Koyanagi-Harada disease.
AB  - INTRODUCTION: Vogt-Koyanagi-Harada (VKH) prognosis depends on early recognition
      and treatment; chronic disease may be developed when either delayed or inadequate
      treatment is performed, whereas other cases despite correct treatment are
      refractory to different drugs and also become chronic. We report a case of
      refractory VKH controlled with rituximab treatment. CASE REPORT: A 41-year-old
      female with painful visual loss and headache was examined. (VA 0.4 in RE and hand
      movements (HM) in LE). Retinal examination demonstrated multiple serous retinal
      detachments in both eyes. High-dose oral steroids were started, followed by
      progressive tapering of prednisone. New acute anterior and posterior relapses
      were achieved, and other immunommodulators were progressively added-new high-dose
      steroid treatment, adalimumab, cyclosporine, and methotrexate-but patient had new
      anterior and posterior recurrences associated with tinnitus and headache. Thus,
      an infusion of 1 g of rituximab was administered after 15 months follow-up; the
      VA was 0.2 in RE and counting fingers in LE. Three additional doses of 1 g each
      were administered 1, 6, and 16 months later. We have achieved a final VA after 34
      months follow-up of 0.2 in RE and HM in LE, with definitive control of
      inflammation, without acute relapses since rituximab was administered.
      CONCLUSION: After searching PubMed/Medline, this is the first report of VKH
      disease treated with rituximab. Additional studies are warranted to confirm the
      efficacy of this new approach for inflammatory control in refractory cases of VKH
      disease.

PMID- 21744182
TI  - Lymphoid proliferations of indeterminate malignant potential arising in adults
      with common variable immunodeficiency disorders: unusual case studies and
      immunohistological review in the light of possible causative events.
AB  - Patients with common variable immunodeficiency disorders (CVIDs) who developed B
      cell lymphoproliferation of indeterminate malignant potential are described in
      order to raise a discussion of the relationship between infection and
      lymphoproliferation in infection prone patients. Those with CVID are at risk of
      developing either polyclonal or monoclonal lymphoproliferation in part due to the
      dysregulation of their adaptive immune systems. The aetiologies of the
      lymphoproliferations are unknown but intriguing; the relevance of infection being
      particularly problematic. The patients described here demonstrate variability in
      preceding infection, age at presentation, response to antibiotics and other types
      of therapy as well as outcome. The question of treatment is also controversial;
      issues include whether antibiotics or chemotherapy are the first line of therapy
      in all patients and whether transformation to aggressive B cell malignancy is
      inevitable or depends on other factors and if so, the length of time for such
      progression.

PMID- 21744183
TI  - Active immunological profile is associated with systemic Sjogren's syndrome.
AB  - BACKGROUND: The aim of this paper was to study the evolution of primary Sjogren's
      syndrome (pSS) immunological profile, its impact on pSS activity and long-term
      evolution in a bicentric cohort of French patients with pSS (n = 445, mean age
      53.6 +/- 14 years, mean follow-up 76.1 +/- 51 months). METHODS: This is a
      retrospective cohort study. RESULTS: Two hundred twelve patients were Sjogren's
      syndrome A (SSA) positive, and 131 were both SSA and Sjogren's syndrome B (SSB)
      positive. Sixty-eight patients (15%) had cryoglobulinemia. Active systemic
      profile (i.e., hypergammaglobulinemia, rheumatoid factor (RF), and anti-Sjogren's
      syndrome A (anti-SSA), anti-Sjogren's syndrome B (anti-SSB) positivity),
      associated with multisystemic involvement, leads to an increased utilization of
      corticosteroid and hydroxychloroquine. Multivariate analysis pointed out
      independent statistical association between hypergammaglobulinemia, anti-SSA,
      anti-SSB, and RF. Cryoglobulinemia is associated with multi-systemic involvement,
      lymphoma, and pSS-related death. CONCLUSION: The subset of patients with active
      immunological profile is characterized by systemic complications leading to
      immunosuppressive drug utilization and polyclonal B-cell activation profile.

PMID- 21744184
TI  - Declining return migration from the United States to Mexico in the late-2000s
      recession: a research note.
AB  - Researchers in the United States and Mexico have variously asserted that return
      migration from the United States to Mexico increased substantially, remained
      unchanged, or declined slightly in response to the 2008-2009 U.S. recession and
      fall 2008 global financial crisis. The present study addresses this debate using
      microdata from 2005 through 2009 from a large-scale, quarterly Mexican household
      survey, the National Survey of Occupation and Employment (ENOE), after first
      validating the ENOE against return-migration estimates from a specialist
      demographic survey, the National Survey of Demographic Dynamics (ENADID).
      Declines in annual return-migration flows of up to a third between 2007 and 2009
      were seen among the predominantly labor-migrant groups of male migrants and all
      18- to 40-year-old migrants with less than a college education; and a decline in
      total return migration was seen in the fourth quarter of 2008 (immediately after
      the triggering of the global financial crisis) compared with the fourth quarter
      of 2007.

PMID- 21744185
TI  - Hybrid gel composed of native heart matrix and collagen induces cardiac
      differentiation of human embryonic stem cells without supplemental growth
      factors.
AB  - Our goal was to assess the ability of native heart extracellular matrix (ECM) to
      direct cardiac differentiation of human embryonic stem cells (hESCs) in vitro. In
      order to probe the effects of cardiac matrix on hESC differentiation, a series of
      hydrogels was prepared from decellularized ECM from porcine hearts by mixing ECM
      and collagen type I at varying ratios. Maturation of cardiac function in embryoid
      bodies formed from hESCs was documented in terms of spontaneous contractile
      behavior and the mRNA and protein expression of cardiac markers. Hydrogel with
      high ECM content (75% ECM, 25% collagen, no supplemental soluble factors)
      increased the fraction of cells expressing cardiac marker troponin T, when
      compared with either hydrogel with low ECM content (25% ECM, 75% collagen, no
      supplemental soluble factors) or collagen hydrogel (100% collagen, with
      supplemental soluble factors). Furthermore, cardiac maturation was promoted in
      high-ECM content hydrogels, as evidenced by the striation patterns of cardiac
      troponin I and by upregulation of Cx43 gene. Consistently, high-ECM content
      hydrogels improved the contractile function of cardiac cells, as evidenced by
      increased numbers of contracting cells and increased contraction amplitudes. The
      ability of native ECM hydrogel to induce cardiac differentiation of hESCs without
      the addition of soluble factors makes it an attractive biomaterial system for
      basic studies of cardiac development and potentially for the delivery of
      therapeutic cells into the heart.

PMID- 21744186
TI  - Do we need individualised prescribing quality assessment? The case of diabetes
      treatment.
AB  - Prescribing quality assessment is increasingly used in improvement programs and
      pay-for-performance policies. Within the area of diabetes many quality indicators
      have been developed. Some measure prescribing on a general level, e.g.
      calculating percentages of patients prescribed any statins. Others are very
      specific, e.g. percentages of patients with an elevated LDL-cholesterol in whom
      lipid-lowering treatment is started unless contraindicated or return to control
      within 3 months. Although the latter seems more precise, we question how far one
      should go in developing such indicators. Using the example of diabetes treatment,
      we highlight the need, opportunities, and feasibility of assessing prescribing
      quality in the context of individualised treatment. We conclude that it is not
      realistic to develop indicators that take all possible aspects of therapy non
      response, intolerance and patient preferences into account. We do recommend
      further development of indicators that better address subpopulations in need of
      adjusted treatment, such as elderly or patients with comorbidity.

PMID- 21744187
TI  - Efficacy and safety of dexmedetomidine versus morphine in post-operative cardiac
      surgery patients.
AB  - OBJECTIVE: To compare the efficacy of dexmedetomidine versus morphine as a
      sedative/analgesic among post-operative cardiac surgery patients. METHOD: A
      randomized controlled open-label study was performed at the cardiothoracic
      intensive care unit of Penang Hospital, Malaysia. A total of 28 patients who
      underwent cardiac surgeries were randomly assigned to receive either
      dexmedetomidine or morphine. Both groups were similar in terms of preoperative
      baseline characteristics. Efficacy measures included sedation scores and pain
      intensity and requirements for additional sedative/analgesic. Mean heart rate and
      arterial blood pressure were used as safety measures. Other measures were
      additional inotropes, extubation time and other concurrent medications. RESULTS:
      The mean dose of dexmedetomidine infused was 0.12 [SD 0.03] MUg kg-1 h-1, while
      that of morphine was 13.2 [SD 5.84] MUg kg-1 h-1. Dexmedetomidine group showed
      more benefits in sedation and pain levels, additional sedative/analgesic
      requirements, and extubation time. No significant differences between the two
      groups for the outcome measures, except heart rate, which was significantly lower
      in the dexmedetomidine group. CONCLUSION: This preliminary study suggests that
      dexmedetomidine was at least comparable to morphine in terms of efficacy and
      safety among cardiac surgery patients. Further studies with larger samples are
      recommended in order to determine the significant effects of the outcome
      measures.

PMID- 21744188
TI  - The provision of current and future sexual health services from community
      pharmacies in Grampian, Scotland.
AB  - OBJECTIVE: Community pharmacies play a vital role in promoting, maintaining and
      improving the health of the local community. This study explored community
      pharmacists' activities and attitudes towards the provision of sexual health
      services (SHS) in North East Scotland, as well as their needs with regard to the
      delivery of current and future SHS. SETTING: North East Scotland. METHODS: A
      questionnaire was conducted of community pharmacists working in community
      pharmacies in Grampian (n = 128). MAIN OUTCOME MEASURES: Self-reported provision
      of sexual health services; attitudes towards current and future sexual health
      services; previous training and perceived training needs; respondent
      demographics. RESULTS: In total, 73% (94/128) of community pharmacists responded.
      The average number of SHS/products per pharmacy was six out of a possible 13
      (range: 4-10). Respondents expressed positive attitudes towards the provision of
      current and future SHS. However, they also reported that they had received little
      or no sexual health training but that they would like to receive training in all
      areas of sexual health. Barriers to the provision of sexual health included
      workload, lack of training and the need for payment for additional services.
      CONCLUSION: Community pharmacists already provide a limited range of sexual
      health services. Community pharmacists, their staff and their premises could be
      used in strategies to reduce unplanned pregnancies, the incidence of sexually
      transmitted infections and to promote respectful and responsible sexual
      behaviour.

PMID- 21744189
TI  - Induction-related cost of patients with acute myeloid leukaemia in France.
AB  - OBJECTIVE: The economic profile of acute myeloid leukaemia (AML) is badly known.
      The few studies published on this disease are now relatively old and include
      small numbers of patients. The purpose of this retrospective study was to
      evaluate the induction-related cost of 500 patients included in the AML 2001
      trial, and to determine the explanatory factors of cost. SETTING: "Induction"
      patient's hospital stay from admission for "induction" to discharge after
      induction. METHOD: The study was performed from the French Public Health
      insurance perspective, restrictive to hospital institution costs. The average
      management of a hospital stay for "induction" was evaluated according to the
      analytical accounting of Besancon University Teaching Hospital and the French
      public Diagnosis-Related Group database. Multiple linear regression was used to
      search for explanatory factors. MAIN OUTCOME MEASURE: Only direct medical costs
      were included: treatment and hospitalisation. RESULTS: Mean induction-related
      direct medical cost was estimated at ?41,852 +/- 6,037, with a mean length of
      hospital stay estimated at 36.2 +/- 10.7 days. After adjustment for age, sex and
      performance status, only two explanatory factors were found: an additional
      induction course and salvage course increased induction-related cost by 38% (+/-
      4) and 15% (+/- 1) respectively, in comparison to one induction. These
      explanatory factors were associated with a significant increase in the mean
      length of hospital stay: 45.8 +/- 11.6 days for 2 inductions and 38.5 +/- 15.5 if
      the patient had a salvage course, in comparison to 32.9 +/- 7.7 for one induction
      (P < 10-4). This result is robust and was confirmed by sensitivity analysis.
      CONCLUSION: Consideration of economic constraints in health care is now a
      reality. Only the control of length of hospital stay may lead to a decrease in
      induction-related cost for patients with AML.

PMID- 21744190
TI  - Implementing a pharmacist-led sequential antimicrobial therapy strategy: a
      controlled before-and-after study.
AB  - Sequential antimicrobial therapy is an important part of antimicrobial
      stewardship and intends to improve the timeliness of switch to oral
      antimicrobials. The aim of this study was to assess the impact of the
      introduction of guidelines and criteria for switching to oral antimicrobials.
      SETTING: The study was conducted in a 753-bed academic hospital in Ireland.
      METHODS: The study was prospective and of controlled before and after design.
      Patients admitted under the care of a medical consultant were screened for
      inclusion. The study was divided into pre-intervention and post-intervention
      phases. Patients admitted and prescribed IV antimicrobials were enrolled into
      either a study group or control group. Post-intervention, the intervention to the
      study group consisted of application of stickers and criteria for switch to oral
      antimicrobial therapy to the drug chart. Pre-intervention in the study group and
      in both phases in the control group, conventional practice of clinical
      pharmacists reviewing drug charts and contacting prescribers to discuss a switch
      to an oral antimicrobial continued. The duration of intravenous treatment, the
      timeliness of switch to oral therapy, length of stay and cost savings were
      measured. MAIN OUTCOME MEASURE: The duration of intravenous antimicrobial therapy
      in the pre-intervention and post-intervention phases in both study and control
      groups. RESULTS: Pre-intervention, 85 courses of IV antimicrobials were
      prescribed to study group patients, compared to 60 in the control group. Post
      intervention, there were 92 courses in the study group and 53 in the control
      group. The duration of IV antimicrobial treatment reduced significantly in the
      study group post-intervention, compared to the control group (P = 0.02). The
      timeliness of the switch also improved significantly in the study group post
      intervention (P = 0.017). No improvement occurred in the control group. The
      median length of stay was not reduced post-intervention. Antimicrobial costs
      reduced by a mean of ?6.41 in the study group post-intervention. CONCLUSION: This
      controlled before and after study demonstrates successful implementation of a
      pharmacist-led antimicrobial stewardship strategy. Duration of IV antimicrobial
      treatment reduced significantly and the timeliness of switch significantly
      improved. This study may be used as a template for the introduction of further
      pharmacist-led antimicrobial stewardship initiatives.

PMID- 21744191
TI  - The role of clinical pharmacist on lipid control in dyslipidemic patients in
      North of Jordan.
AB  - OBJECTIVE: The purpose of this study is to investigate the effectiveness of
      introducing clinical pharmacy services in achieving goal lipid profile in
      dyslipidemia patients in North of Jordan. Setting the study was carried out in a
      primary care facility in North of Jordan. METHODS: One hundred fifty two
      dyslipidemia patients were randomized into intervention and control groups and
      followed for 6 months period. Intervention group patients were followed
      intensively by a clinical pharmacist who worked closely with physicians in
      controlling lipid profiles according to the third edition of recommendations by
      The National Cholesterol Education Program Adult Treatment Panel, control group
      patients were provided with standard medical care. Main outcome measure percent
      of patients at their low density lipoprotein cholesterol target in the
      intervention group compared to percent of patients at their low density
      lipoprotein cholesterol target in the control group by the end of the study.
      RESULTS: One hundred twenty five patients completed the study duration. After 6
      months, 94.5% of intervention group patients and 71.2 % of control group patients
      reached their goal low density lipoprotein cholesterol levels (P value < 0.001,
      Pearson Chi-Square test) compared to 24.7 and 28.8% respectively at baseline.
      Majority of pharmacist recommendations (90.4%) were followed by physicians and
      overall lipid lowering agents use was increased to 91.8% in intervention group
      patients and 86.5% in control group patients compared to 69.9 and 78.8%
      respectively at baseline. CONCLUSION: Implementing clinical pharmacy services in
      Jordan has improved the lipid profiles of dyslipidemic patients.

PMID- 21744192
TI  - The outpatient utilization of non-steroidal anti-inflammatory drugs in South
      Backa District, Serbia.
AB  - OBJECTIVE: To evaluate the utilization of non-steroidal anti-inflammatory drugs
      (NSAIDs) in South Backa District (SBD), Serbia. SETTING: State-owned and private
      pharmacies in SBD, a northern district of Serbia, with 605,720 inhabitants
      (according to the 2008 census). METHOD: Data on the number of packages, size of
      packages, and retail price of NSAIDs (Anatomical Therapeutic Chemical (ATC) group
      M01A) from 1 January to 31 March 2008 were obtained from all state-owned and
      private pharmacies in SBD. This included NSAIDs bought without prescription and
      those issued by prescription (on the Health Insurance Companies List for
      Reimbursement). The number of defined daily doses/1000 inhabitants/day (DDD/1000
      inh/day) was calculated. Within the DU90% (drug utilization 90%) segment, the
      proportion of high-, medium- and low-risk NSAIDs with respect to the risk of
      gastrointestinal (GI) bleeding was determined. Price/DDD was also calculated.
      MAIN OUTCOME MEASURE: Consumption of drugs expressed as DDD/1000 inh/day.
      RESULTS: The total consumption of NSAIDs over a 3-month period was 48.31 DDD/1000
      inh/day. Only four drugs were within DU90%: diclofenac, ibuprofen, nimesulide and
      meloxicam (62.14, 19.87, 5.77, and 5.73% of total NSAID consumption,
      respectively). All dispensed NSAIDs within the DU90% segment except nimesulide
      (which was exclusively purchased without prescription) were nearly equally
      purchased without prescription and issued by prescription. The average price per
      DDD within the DU90% segment was 0.17 Euro/DDD, whereas it was 0.30 Euro/DDD for
      NSAIDs beyond the DU90% segment. The pattern of use of NSAIDs according to their
      GI risk showed that medium-risk diclofenac accounted for 66.45%, whereas low-risk
      ibuprofen was estimated to be 21.25% within the DU90% segment. CONCLUSION:
      Factors other than evidence-based medicine (such as poor health education in the
      past that led to long-lasting consequences on the cultural behaviour of the
      general population as well as on the prescribing habits of physicians) have a
      dominating impact on the use of NSAIDs in SBD. Targeted education from
      independent sources in the prescribing, dispensing and use of drugs is required
      to improve the quality of prescription and use of NSAIDs in Serbia.

PMID- 21744194
TI  - The British Society of Urogynaecology.

PMID- 21744196
TI  - Interfaces between orthodontic and periodontal treatment: their current status.
AB  - The contextual relationships between orthodontics and periodontology are diverse
      and complex. While the consequences of orthodontic tooth movements are discussed
      in terms of possible damage and improvements in the long-term health of
      periodontal tissues orthodontic treatment of adults is a routine clinical
      procedure nowadays, even in patients presenting already-damaged periodontal
      tissues. As developments in both fields have been so rapid, there is a constant
      need for evidence-based concepts in this interdisciplinary field. The goal of
      this review was to discuss the latest aspects of interdisciplinary treatment and
      to reflect on the latest developments in research. A treatment scheme is also
      presented which aims to facilitate coordination of the orthodontic treatment of
      patients with periodontal diseases.

PMID- 21744197
TI  - Prevalence of Helicobacter pylori in the adolescent oral cavity: dependence on
      orthodontic therapy, oral flora and hygiene.
AB  - BACKGROUND: Helicobacter pylori (HP) infection usually occurs in childhood. While
      there are various studies on the prevalence of HP in dental plaque, ours is the
      first to analyze its prevalence during orthodontic therapy and its interaction
      with competitive bacteria in adolescents. SUBJECTS AND METHODS: The prevalence of
      HP was examined before and during the first 12 weeks of orthodontic therapy with
      fixed appliances in 11 patients with a mean age of 12.7 years. A total of 93
      plaque samples were analyzed using PCR. The data acquired at every consultation
      were the following: PCR analysis of dental plaque and (13)C urea breath tests for
      HP, quantitative analyses of saliva for Lactobacilli and Streptococcus mutans,
      the interproximal plaque index (API), and sulcus bleeding index (SBI). RESULTS:
      The prevalence of HP in plaque was 82% before orthodontic therapy, dropping to
      54% during therapy (t test, p<=0.05). In contrast to HP's prevalence, the
      Lactobacilli count rose (p<=0.05). The number of Streptococcus mutans bacteria in
      saliva decreased during orthodontic therapy (p<=0.05). CONCLUSION: The prevalence
      of HP in dental plaque amounted to 82%. Orthodontic treatment did not reduce its
      prevalence. The prevalence of Lactobacilli was inversely proportional to that of
      HP.

PMID- 21744198
TI  - Overjet correction and space closure mechanisms for Class II treatment by
      extracting the maxillary first molars.
AB  - OBJECTIVE: To analyze the mechanism of overjet correction and space closure when
      treating Class II Division 1 patients by extracting the maxillary first molars.
      PATIENTS AND METHODS: A total of 100 prospective, consecutively treated Class II
      Division 1 patients (45 female, 55 male; 10.5-17.2 years old). Standardized
      lateral cephalograms prior to and after treatment were evaluated via a modified
      sagittal occlusion analysis (SO analysis). RESULTS: The mean degree of overjet
      correction was 5.2 mm (95% CI = 4.8-5.6 mm) and was on average achieved by means
      of 1.7 mm skeletal and 3.5 mm dental changes. The relationship between the
      premolars improved by 4.8 mm toward a Class I relationship, facilitated by 1.7 mm
      skeletal and 3.1 mm dental changes. The 11.3 mm space closure in the maxillary
      first-molar extraction area resulted from distalization of the second premolars
      (1.4 mm) and a mesialization of the second molars (9.9 mm). CONCLUSIONS: Overjet
      correction was essentially achieved by a retrusion of the upper incisors, as well
      as by ventral growth of the lower jaw and protrusion of the lower incisors. Space
      closure was only partly achieved by distalization of the premolars.

PMID- 21744199
TI  - Does thread design influence relative bone-to-implant contact rate of palatal
      implants?
AB  - AIM: To determine histologically whether (a) changing the thread design between
      first- and second-generation palatal implants (Straumann, Basel, Switzerland)
      influences the bone-to-implant contact (BIC) rate of palatal implants subjected
      to conventional loading, and (b) whether histological evidence of peri
      implantitis appears in this setting. PATIENTS AND METHODS: Patients who had
      received an orthodontic palatal implant for skeletal anchorage between January
      1998 and December 2007 were examined. First-generation palatal implants
      (Straumann, Basel, Switzerland) 3.3 mm in diameter and 6 mm or 4 mm long were
      used, as were second-generation implants 4.1 mm in diameter and 4.2 mm long.
      After completion of active orthodontic treatment, the implants were removed and
      prepared for histological investigation. This study was designed as a comparative
      analysis of a series of two cases: 28 explanted first-generation (n = 14) and
      second-generation (n = 14) palatal implants were analyzed. RESULTS: Bone healing
      was achieved with all implants. Both types of implants revealed a mean bone-to
      implant contact (BIC) rate that was nearly equal: 80.7% (SD 10.7%) for the first
      generation and 81% (SD 13.1%) for the second-generation implants. Bone resorption
      was only observed in 5 palatal implants (3/14 of the first, and 2/14 of the
      second generation). CONCLUSION: Despite differing thread designs, second
      generation palatal implants revealed similar bone-to-implant contact rates as did
      those of the first generation. Few patients presented bone resorption in the peri
      implant bone.

PMID- 21744200
TI  - Expectations, acceptance and preferences of patients in treatment with
      orthodontic mini-implants: part II: implant removal.
AB  - OBJECTIVE: The objective of this study was to compare mechanical and manual
      techniques to remove orthodontic mini-implants. We also investigated whether the
      treated patients preferred local anesthetics. The study's focus is on the
      patients' perceptions and the resulting preferences. PATIENTS AND METHODS: A
      total of 25 patients were randomly assigned to Group A or Group B. In Group A,
      the mini-implants were removed with a handpiece, while the Group-B patients' mini
      implants were removed completely by hand. In addition, all patients received an
      injection of local anesthetic into one half of the jaw. No anesthetic was used on
      the other half of the jaw. The patients were asked about their pain perception
      before treatment, immediately after treatment and one day after treatment.
      RESULTS: We observed no significant differences between the two groups with
      respect to the intensity of their symptoms. However, the noise associated with
      the handpiece was found to be unpleasant and tended to lead to more symptoms than
      when no handpiece was used. Pain perceived during mini-implant removal was
      relatively slight and not much affected by the use of local anesthetics. The most
      severe symptoms were associated with the injection itself. The non-injected side
      experienced significantly less discomfort and was thus the preferred side in both
      groups. CONCLUSION: The patients tolerated the two removal procedures equally
      well. As the noise associated with the handpiece increased discomfort, manual
      removal of the mini-implants is preferable. As regards the injection technique,
      our results show that local anesthesia during removal does not provide a benefit.
      The most pain was caused by the injection, not by removal of the mini-implants.

PMID- 21744201
TI  - The German version of the child perceptions questionnaire on oral health-related
      quality of life (CPQ-G11-14): population-based norm values.
AB  - OBJECTIVE: The aim of this study was to determine the frequency of oral health
      related quality of life (OHRQoL) impairment and to establish norm values for the
      German version of the Child Perceptions Questionnaire (CPQ-G11-14, 35 questions)
      in the general population aged 11 to 14 years. SUBJECTS AND METHODS: Data were
      collected in a national survey (n=1,597, mean age: 12.5 +/- 1.2 years, 49.3%
      female) and subjects sampled using a multistage technique. OHRQoL was measured
      with the CPQ-G11-14, which was presented in a personal interview. Norm values
      were computed for the CPQ-G11-14 summary score (simple sum of all item
      responses). The CPQ-G11-14 summary score distribution was described by empirical
      cumulative distribution functions. Because orthodontic treatment was closely
      associated with CPQ-G11-14 summary scores, percentile-based norms were stratified
      by this variable. RESULTS: The CPQ-G11-14 mean was 12.6 +/- 15.9 units. There was
      no influence of age (p>0.05) or gender (p>0.05) on the CPQ-G summary scores, but
      the summary scores varied according to orthodontic treatment status (p<0.001).
      Among the general population sample, CPQ-G11-14 scores of the 50% less-impaired
      subjects were <=7. The same percentage of subjects undergoing orthodontic
      treatment had scores of <=13 and those without orthodontic treatment had scores
      of <=5. We observed scores of <=32 points in 90% of the population. That figure
      was <=50 points for subjects undergoing orthodontic treatment and <=21 points for
      those without orthodontic treatment. The most frequent problems the children and
      adolescents reported (CPQ-G answers "often" and "very often") were "breathing
      through the mouth" (13.0%), "mouth sores" (4.4%) and "bad breath" (4.3%).
      CONCLUSION: The norm values we present provide a frame of reference for future
      cross-sectional studies in the general population and in patient populations with
      specific oral conditions when measuring OHRQoL by CPQ-G11-14 in children and
      adolescents aged 11 to 14 years old.

PMID- 21744203
TI  - Transient receptor potential cation channels in pancreatic beta cells.
AB  - There is now overwhelming evidence that TRP channels might play a significant
      role in the regulation of insulin release from pancreatic beta cells, which is
      until now insufficiently recognized. TRP channels are abundantly expressed on
      beta cells. The focus of this review will be on cation channels from the
      melastatin TRP -subfamily. We will discuss how TRPM channels can influence Ca(2+)
      signaling in beta cells. Knock out models of TRPM2 and TRPM5, which show a pre
      diabetic phenotype, will be illustrative for this purpose. Based on these
      insights, TRPM5 will be critically evaluated as a potential drug target for
      diabetes type II therapy, which has received currently a high interest of the
      pharmaceutical industry. In addition, an unexpected role of the TRP channel TRPM3
      as a gatekeeper of zinc, which is required for insulin storage, will be
      considered. Finally, we will critically discuss the use of mouse models for the
      unraveling of basic mechanisms of insulin release. The study of the role of TRP
      channels in the regulation of insulin release is of wide interest for fundamental
      research, evaluation of molecular mechanisms of disease and exploration of novel
      drug targets for metabolic diseases.

PMID- 21744205
TI  - Introduction: from brains to the machines of the future.

PMID- 21744206
TI  - Emergent feature sensitivity in a model of the auditory thalamocortical system.
AB  - If, as is widely believed, perception is based upon the responses of neurons that
      are tuned to stimulus features, then precisely what features are encoded and how
      do neurons in the system come to be sensitive to those features? Here we show
      differential responses to ripple stimuli can arise through exposure to formative
      stimuli in a recurrently connected model of the thalamocortical system which
      exhibits delays, lateral and recurrent connections, and learning in the form of
      spike timing dependent plasticity.

PMID- 21744207
TI  - STDP pattern onset learning depends on background activity.
AB  - Spike-timing dependent plasticity is a learning mechanism used extensively within
      neural modelling. The learning rule has previously been shown to allow a neuron
      to learn a repeated spatio-temporal pattern among its afferents and respond at
      its onset. In this study we reconfirm these previous results and additionally
      adduce that such learning is dependent on background activity. Furthermore, we
      found that the onset learning is unstable when in a noisy framework.
      Specifically, if the level of background activity changes during learning the
      response latency of a neuron may increase and with the adding of additional noise
      the distribution of response latencies degrades. Consequently, we present
      preliminary insights into the neuron's encoding: viz. that a neuron may encode
      the coincidence of spikes from a subsection of a stimulus' afferents, but the
      temporal precision of the onset response depends on some background activity,
      which must be similar to that present during learning.

PMID- 21744208
TI  - Emergence of small-world structure in networks of spiking neurons through STDP
      plasticity.
AB  - In this work, we use a complex network approach to investigate how a neural
      network structure changes under synaptic plasticity. In particular, we consider a
      network of conductance-based, single-compartment integrate-and-fire excitatory
      and inhibitory neurons. Initially the neurons are connected randomly with
      uniformly distributed synaptic weights. The weights of excitatory connections can
      be strengthened or weakened during spiking activity by the mechanism known as
      spike-timing-dependent plasticity (STDP). We extract a binary directed connection
      matrix by thresholding the weights of the excitatory connections at every
      simulation step and calculate its major topological characteristics such as the
      network clustering coefficient, characteristic path length and small-world index.
      We numerically demonstrate that, under certain conditions, a nontrivial small
      world structure can emerge from a random initial network subject to STDP
      learning.

PMID- 21744209
TI  - Coupling BCM and neural fields for the emergence of self-organization consensus.
AB  - Human beings interact with the environment through different modalities, i.e.
      perceptions and actions, processed in the cortex by dedicated brain areas. These
      areas are self-organized, so that spatially close neurons are sensitive to close
      stimuli, providing generalization from previously learned examples. Although
      perceptive flows are picked up by different spatially separated sensors, their
      processings are not isolated. On the contrary, they are constantly interacting,
      as illustrated by the McGurk effect. When the auditory stimulus /ba/ and the /ga/
      lip movement are presented simultaneously, people perceive a /da/, which does not
      correspond to any of the stimuli. Merging several stimuli into one multimodal
      perception reduces ambiguities and noises and is essential to interact with the
      environment. This article proposes a model for modality association, inspired by
      the biological properties of the cortex. The model consists of modality maps
      interacting through an associative map to raise a consistent multimodal
      perception of the environment. We propose the coupling of BCM learning rule and
      neural maps to obtain the decentralized and unsupervised self-organization of
      each modal map influenced by the multisensory context. We obtain local self
      organization of modal maps with various inputs and discretizations.

PMID- 21744210
TI  - Alpha and theta rhythm abnormality in Alzheimer's Disease: a study using a
      computational model.
AB  - Electroencephalography (EEG) studies in Alzheimer's Disease (AD) patients show an
      attenuation of average power within the alpha band (7.5-13 Hz) and an increase of
      power in the theta band (4-7 Hz). Significant body of evidence suggest that
      thalamocortical circuitry underpin the generation and modulation of alpha and
      theta rhythms. The research presented in this chapter is aimed at gaining a
      better understanding of the neuronal mechanisms underlying EEG band power changes
      in AD which may in the future provide useful biomarkers towards early detection
      of the disease and for neuropharmaceutical investigations. The study is based on
      a classic computational model of the thalamocortical circuitry which exhibits
      oscillation within the theta and the alpha bands. We are interested in the change
      in model oscillatory behaviour corresponding with changes in the connectivity
      parameters in the thalamocortical as well as sensory input pathways. The synaptic
      organisation as well as the connectivity parameter values in the model are
      modified based on recent experimental data from the cat thalamus. We observe that
      the inhibitory population in the model plays a crucial role in mediating the
      oscillatory behaviour of the model output. Further, increase in connectivity
      parameters in the afferent and efferent pathways of the inhibitory population
      induces a slowing of the output power spectra. These observations may have
      implications for extending the model for further AD research.

PMID- 21744211
TI  - Oscillatory neural network for image segmentation with biased competition for
      attention.
AB  - We study the emergent properties of an artificial neural network which combines
      segmentation by oscillations and biased competition for perceptual processing.
      The aim is to progress in image segmentation by mimicking abstractly the way how
      the cerebral cortex works. In our model, the neurons associated with features
      belonging to an object start to oscillate synchronously, while competing objects
      oscillate with an opposing phase. The emergent properties of the network are
      confirmed by experiments with artificial image data.

PMID- 21744212
TI  - Internal simulation of perceptions and actions.
AB  - We present a study of neural network architectures able to internally simulate
      perceptions and actions. All these architectures employ the novel Associative
      Self-Organizing Map (A-SOM) as a perceptual neural network. The A-SOM develops a
      representation of its input space, but in addition also learns to associate its
      activity with an arbitrary number of additional (possibly delayed) inputs. One
      architecture is a bimodal perceptual architecture whereas the others include an
      action neural network adapted by the delta rule. All but one architecture are
      recurrently connected. We have tested the architectures with very encouraging
      simulation results. The bimodal perceptual architecture was able to simulate
      appropriate sequences of activity patterns in the absence of sensory input for
      several epochs in both modalities. The architecture without recurrent connections
      correctly classified 100% of the training samples and 80% of the test samples.
      After ceasing to receive any input the best of the architectures with recurrent
      connections was able to continue to produce 100% correct output sequences for 28
      epochs (280 iterations), and then to continue with 90% correct output sequences
      until epoch 42.

PMID- 21744213
TI  - Building neurocognitive networks with a distributed functional architecture.
AB  - In the past few decades, behavioral and cognitive science have demonstrated that
      many human behaviors can be captured by low-dimensional observations and models,
      even though the neuromuscular systems possess orders of magnitude more potential
      degrees of freedom than are found in a specific behavior. We suggest that this
      difference, due to a separation in the time scales of the dynamics guiding neural
      processes and the overall behavioral expression, is a key point in understanding
      the implementation of cognitive processes in general. In this paper we use
      Structured Flows on Manifolds (SFM) to understand the organization of behavioral
      dynamics possessing this property. Next, we discuss how this form of behavioral
      dynamics can be distributed across a network, such as those recruited in the
      brain for particular cognitive functions. Finally, we provide an example of an
      SFM style functional architecture of handwriting, motivated by studies in human
      movement sciences, that demonstrates hierarchical sequencing of behavioral
      processes.

PMID- 21744214
TI  - Reverse engineering for biologically inspired cognitive architectures: a critical
      analysis.
AB  - Research initiatives on both sides of the Atlantic try to utilize the operational
      principles of organisms and brains to develop biologically inspired, artificial
      cognitive systems. This paper describes the standard way bio-inspiration is
      gained, i.e. decompositional analysis or reverse engineering. The indisputable
      complexity of brain and mind raise the issue of whether they can be understood by
      applying the standard method. Using Robert Rosen's modeling relation, the
      scientific analysis method itself is made a subject of discussion. It is
      concluded that the fundamental assumption of cognitive science, i.e. complex
      cognitive systems are decomposable, must be abandoned. Implications for
      investigations of organisms and behavior as well as for engineering artificial
      cognitive systems are discussed.

PMID- 21744215
TI  - Competition in high dimensional spaces using a sparse approximation of neural
      fields.
AB  - The Continuum Neural Field Theory implements competition within topologically
      organized neural networks with lateral inhibitory connections. However, due to
      the polynomial complexity of matrix-based implementations, updating dense
      representations of the activity becomes computationally intractable when an
      adaptive resolution or an arbitrary number of input dimensions is required. This
      paper proposes an alternative to self-organizing maps with a sparse
      implementation based on Gaussian mixture models, promoting a trade-off in
      redundancy for higher computational efficiency and alleviating constraints on the
      underlying substrate.This version reproduces the emergent attentional properties
      of the original equations, by directly applying them within a continuous
      approximation of a high dimensional neural field. The model is compatible with
      preprocessed sensory flows but can also be interfaced with artificial systems.
      This is particularly important for sensorimotor systems, where decisions and
      motor actions must be taken and updated in real-time. Preliminary tests are
      performed on a reactive color tracking application, using spatially distributed
      color features.

PMID- 21744216
TI  - Informational theories of consciousness: a review and extension.
AB  - In recent years a number of people have suggested that there is a close link
      between conscious experience and the differentiation and integration of
      information in certain areas of the brain. The balance between differentiation
      and integration is often called information integration, and a number of
      algorithms for measuring it have been put forward, which can be used to make
      predictions about consciousness and to understand the relationships between
      neurons in a network. One of the key problems with the current information
      integration measures is that they take a lot of computer processing power, which
      limits their application to networks of around a dozen neurons. There are also
      more general issues about whether the current algorithms accurately reflect the
      consciousness associated with a system. This paper addresses these issues by
      exploring a new automata-based algorithm for the calculation of information
      integration. To benchmark different approaches we implemented the Balduzzi and
      Tononi algorithm as a plugin to the SpikeStream neural simulator, and used it to
      carry out some preliminary comparisons of the liveliness and Phi measures on
      simple four neuron networks.

PMID- 21744217
TI  - Hippocampal categories: a mathematical foundation for navigation and memory.
AB  - It goes without saying that in science, experiments are essential; hypothesis
      need to be contrasted against empirical results in order to build scientific
      theories. In a system of overwhelming complexity like the brain, it is very
      likely that hidden variables, unknown by the experimentalist, are interacting
      with those few elements of which the values are expected and can be validated or
      rejected in the laboratory. Thus, at the end of the day, the experimentalist is
      refuting or validating tentative models that are somehow prisoners of the lack of
      knowledge about the structure of the system. The global picture being missing, a
      key is to look for the fundamental structure which must be found not in the
      objects, but in the relationships between the objects-their morphisms. How
      components at the same level interact (the objects here being neurons) and how
      superior levels constrain those levels below and emerge from those above is
      tackled here with a mathematical tooling. The mathematical theory of categories
      is proposed as a valid foundational framework for theoretical modeling in brain
      sciences.

PMID- 21744218
TI  - The role of feedback in a hierarchical model of object perception.
AB  - We present a model which stems from a well-established model of object
      recognition, HMAX, and show how this feedforward system can include feedback,
      using a recently proposed architecture which reconciles biased competition and
      predictive coding approaches. Simulation results show successful feedforward
      object recognition, including cases of occluded and illusory images. Recognition
      is both position and size invariant. The model also provides a functional
      interpretation of the role of feedback connectivity in accounting for several
      observed effects such as enhancement, suppression and refinement of activity in
      lower areas. The model can qualitatively replicate responses in early visual
      cortex to occluded and illusory contours; and fMRI data showing that high-level
      object recognition reduces activity in lower areas. A Gestalt-like mechanism
      based on collinearity, co-orientation and good continuation principles is
      proposed to explain illusory contour formation which allows the system to adapt a
      single high-level object prototype to illusory Kanizsa figures of different
      sizes, shapes and positions. Overall the model provides a biophysiologically
      plausible interpretation, supported by current experimental evidence, of the
      interaction between top-down global feedback and bottom-up local evidence in the
      context of hierarchical object perception.

PMID- 21744219
TI  - Machine free will: is free will a necessary ingredient of machine consciousness?
AB  - Sooner or later, machine consciousness will have to address the elusive notion of
      free will either to dismiss it or to produce a machine implementation. It is
      unclear whether freedom and consciousness are independent aspects of the human
      mind or by-product of the same underlying structure. Here, the relevant
      literature is reviewed focusing on the connection between determinism and freedom
      usually explored by compatibilists. Eventually, a tentative model for machine
      free will is outlined.

PMID- 21744220
TI  - Natural evolution of neural support vector machines.
AB  - Two different neural implementations of support vector machines are described and
      applied to one-shot trainable pattern recognition. The first model is based on
      oscillating associative memory and is mapped to the olfactory system. The second
      model is founded on competitive queuing memory originally employed for generating
      motor action sequences in the brain. Both models include forward pathways where a
      stream of support vectors is evoked from memory and merges with sensory input to
      produce support vector machine classifications. Misclassified events are
      imprinted as new support vector candidates. Support vector machine weights are
      tuned by virtual experimentation in sleep. Recalled training examples masquerade
      as sensor input and feedback from the classification process drives a learning
      process where support vector weights are optimized. For both support vector
      machine models it is demonstrated that there is a plausible evolutionary path
      from a simple hard-wired pattern recognizer to a full implementation of a
      biological kernel machine. Simple and individually beneficial modifications are
      accumulated in each step along this path. Neural support vector machines can
      apparently emerge by natural processes.

PMID- 21744221
TI  - Self-conscious robotic system design process--from analysis to implementation.
AB  - Developing robotic systems endowed with self-conscious capabilities means
      realizing complex sub-systems needing ad-hoc software engineering techniques for
      their modelling, analysis and implementation. In this chapter the whole process
      (from analysis to implementation) to model the development of self-conscious
      robotic systems is presented and the new created design process, PASSIC,
      supporting each part of it, is fully illustrated.

PMID- 21744222
TI  - Simulating visual qualia in the CERA-CRANIUM cognitive architecture.
AB  - The concept of qualia poses a central problem in the framework of consciousness
      studies. Despite it being a controversial issue even in the study of human
      consciousness, we argue that qualia can be complementarily studied using
      artificial cognitive architectures. In this work we address the problem of
      defining qualia in the domain of artificial systems, providing a model of
      "artificial qualia". Furthermore, we partially apply the proposed model to the
      generation of visual qualia using the cognitive architecture CERA-CRANIUM, which
      is modeled after the global workspace theory of consciousness. It is our aim to
      define, characterize and identify artificial qualia as direct products of a
      simulated conscious perception process. Simple forms of the apparent motion
      effect are used as the basis for a preliminary experimental setting focused on
      the simulation and analysis of synthetic visual experience. In contrast with the
      study of biological brains, the inspection of the dynamics and transient inner
      states of the artificial cognitive architecture can be performed effectively,
      thus enabling the detailed analysis of covert and overt percepts generated by the
      system when it is confronted with specific visual stimuli. The observed states in
      the artificial cognitive architecture during the simulation of apparent motion
      effects are used to discuss the existence of possible analogous mechanisms in
      human cognition processes.

PMID- 21744223
TI  - The Ouroboros Model, selected facets.
AB  - The Ouroboros Model features a biologically inspired cognitive architecture. At
      its core lies a self-referential recursive process with alternating phases of
      data acquisition and evaluation. Memory entries are organized in schemata. The
      activation at a time of part of a schema biases the whole structure and, in
      particular, missing features, thus triggering expectations. An iterative
      recursive monitor process termed 'consumption analysis' is then checking how well
      such expectations fit with successive activations. Mismatches between
      anticipations based on previous experience and actual current data are
      highlighted and used for controlling the allocation of attention. A measure for
      the goodness of fit provides feedback as (self-) monitoring signal. The basic
      algorithm works for goal directed movements and memory search as well as during
      abstract reasoning. It is sketched how the Ouroboros Model can shed light on
      characteristics of human behavior including attention, emotions, priming,
      masking, learning, sleep and consciousness.

PMID- 21744224
TI  - Prostate cancer diagnostics: innovative imaging in case of multiple negative
      biopsies.
AB  - OBJECTIVE: According to international guidelines, a primary set of TRUS-guided
      systematic biopsy should consist of 10-12 tissue samples. If a clinical suspicion
      of a prostate carcinoma persists, a secondary biopsy session should also involve
      10-12 samples. However, if there still is a clinical suspicion of prostate cancer
      is there a role for innovative imaging guided biopsies? MATERIALS AND METHODS:
      The available innovative imaging techniques range from MRI, Doppler techniques
      with and without contrast agents, a renaissance of elastography to computer
      assisted evaluation of TRUS signal information. RESULT: All of these methods
      attempt to make more specific statements on the imaged tissue. Before routine
      clinical use, a review of the literature is recommended to be able to
      differentiate between the different methods. Sophisticated modern MRI techniques
      allow for excellent high-resolution prostate imaging. However, MRI guided
      biopsies so far are not routine practice and are not recommended in urological
      guidelines. A literature review reflects differences in stage of development,
      biopsy performance and clinical validity of the different imaging modalities.
      Elastography, contrast imaging and C-TRUS/ANNA guided biopsies have been
      investigated in clinical trails suggesting possible benefits over additional
      systematic random biopsies alone. Because of the differences in design and
      clinical maturity of the innovative imaging methods, it is essential to be able
      to inform the patients about individual evidence-based performance prior to its
      clinical utilization. CONCLUSION: The ideal time for innovative imaging
      techniques seems to be in patients with multiple series of negative systematic
      biopsies possibly leading to a more specific PCa detection. However, patients
      often ask for a qualitative diagnostic approach right from the beginning. This
      should only be performed after educating the patient on the experimental and 'non
      guideline-conform' character of such a proceeding.

PMID- 21744225
TI  - Service use and costs for people with headache: a UK primary care study.
AB  - This paper aims to estimate the service and social costs of headache presenting
      in primary care and to identify predictors of headache costs. Patients were
      recruited from GP practices in England and service use and lost employment
      recorded. Predictors of cost were identified using regression models. Service and
      social costs were available on 288 and 282 patients, respectively. Average
      service costs over 3 months were L117 whilst total costs (including lost
      production) were L582. Patients referred to neurologists had service costs that
      were L82 higher than those not referred (90% CI L36-L128). Costs including lost
      employment were higher by L150, but this was not significant (90% CI -L139-L439).
      The annual mean service and social costs, weighted to represent population rates
      of referral, were L468 and L2328, respectively. Higher costs were significantly
      related to pain. Age was linked to higher service costs and lower social costs.
      The figures extrapolated to the whole of the UK suggest L956 million due to
      service use and L4.8 billion including lost employment. These are likely to be
      underestimates because many people experiencing headaches do not consult their
      GP.

PMID- 21744226
TI  - Classification and clinical features of headache patients: an outpatient clinic
      study from China.
AB  - This study aimed to analyze and classify the clinical features of headache in
      neurological outpatients. A cross-sectional study was conducted consecutively
      from March to May 2010 for headache among general neurological outpatients
      attending the First Affiliated Hospital of Chongqing Medical University. Personal
      interviews were carried out and a questionnaire was used to collect medical
      records. Diagnosis of headache was according to the International classification
      of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for
      19.5% of the general neurology clinic outpatients. A total of 843 (50.1%)
      patients were defined as having primary headache, 454 (27%) secondary headache,
      and 386 (23%) headache not otherwise specified (headache NOS). For primary
      headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8
      (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine
      patients suffered (1) more severe headache intensity, (2) longer than 6 years of
      headache history and (3) more common analgesic medications use than TTH ones (p <
      0.001).TTH patients had more frequent episodes of headaches than migraine
      patients, and typically headache frequency exceeded 15 days/month (p < 0.001);
      22.8% of primary headache patients were defined as chronic daily headache. Almost
      20% of outpatient visits to the general neurology department were of headache
      patients, predominantly primary headache of migraine and TTH. In outpatient
      headaches, more attention should be given to headache intensity and duration of
      headache history for migraine patients, while more attention to headache
      frequency should be given for the TTH ones.

PMID- 21744227
TI  - [Hand in hand : when every second counts in an emergency].

PMID- 21744228
TI  - Selection for low-temperature germinability on the short arm of chromosome 3 in
      rice cultivars adapted to Hokkaido, Japan.
AB  - In plant breeding with intensive selection, the haplotype patterns in the
      targeted chromosomal regions may become monogenic among local populations with
      the most desirable combination of loci. This study demonstrated that the
      chromosomal region surrounding qLTG3-1 was under selection during rice breeding
      programs in a local region of Japan, Hokkaido. qLTG3-1 is a major quantitative
      trait loci controlling tolerance to low-temperature at the seed germination stage
      in rice, termed low-temperature germinability. A clear association between qLTG3
      1 alleles and low-temperature germinability was detected among 64 rice cultivars
      from Hokkaido. The allele with a loss-of-function mutation seemed to be selected
      during rice breeding programs. Comparison of haplotype patterns along with the
      short arm of chromosome 3 revealed that the selection of qLTG3-1 alleles was
      focused on a distinct chromosomal region of at most 130 kb. In the short arm of
      chromosome 3, two major traits associated with the adaptability to local
      conditions have been identified; eating quality and heading date. This study
      demonstrated that recombinant haplotype patterns for these traits might shape the
      adaptability to local environmental conditions and market demands during rice
      breeding programs in addition to the selection of qLTG3-1 alleles. The present
      results provide new opportunities for the design of hybridization combinations
      based on the haplotype patterns of chromosomal regions under selection during
      rice breeding programs in local regions.

PMID- 21744229
TI  - Identification of novel genomic regions associated with resistance to Pyrenophora
      tritici-repentis races 1 and 5 in spring wheat landraces using association
      analysis.
AB  - Tan spot, caused by Pyrenophora tritici-repentis, is a major foliar disease of
      wheat worldwide. Host plant resistance is the best strategy to manage this
      disease. Traditionally, bi-parental mapping populations have been used to
      identify and map quantitative trait loci (QTL) affecting tan spot resistance in
      wheat. The association mapping (AM) could be an alternative approach to identify
      QTL based on linkage disequilibrium (LD) within a diverse germplasm set. In this
      study, we assessed resistance to P. tritici-repentis races 1 and 5 in 567 spring
      wheat landraces from the USDA-ARS National Small Grains Collection (NSGC). Using
      832 diversity array technology (DArT) markers, QTL for resistance to P. tritici
      repentis races 1 and 5 were identified. A linear model with principal components
      suggests that at least seven and three DArT markers were significantly associated
      with resistance to P. tritici-repentis races 1 and 5, respectively. The DArT
      markers associated with resistance to race 1 were detected on chromosomes 1D, 2A,
      2B, 2D, 4A, 5B, and 7D and explained 1.3-3.1% of the phenotypic variance, while
      markers associated with resistance to race 5 were distributed on 2D, 6A and 7D,
      and explained 2.2-5.9% of the phenotypic variance. Some of the genomic regions
      identified in this study correspond to previously identified loci responsible for
      resistance to P. tritici-repentis, offering validation for our AM approach. Other
      regions identified were novel and could possess genes useful for resistance
      breeding. Some DArT markers associated with resistance to race 1 also were
      localized in the same regions of wheat chromosomes where QTL for resistance to
      yellow rust, leaf rust and powdery mildew, have been mapped previously. This
      study demonstrates that AM can be a useful approach to identify and map novel
      genomic regions involved in resistance to P. tritici-repentis.

PMID- 21744230
TI  - Risk factors for rejection for morphological reasons of heart valves for
      transplantation.
AB  - The study aim was to identify risk factors for morphological rejection of aortic
      and pulmonary valves for transplantation that could be used to optimize donor
      selection. The files of all Dutch heart valve donors, donating in a 2.5 years
      period, whose hearts were processed at Heart Valve Bank Rotterdam, were reviewed
      for all factors that could be relevant for valve rejection and related to outcome
      of morphological assessment of the valves. Valves were retrieved from 813
      deceased Dutch donors, 24.1% also donating organs. For 797 aortic and 767
      pulmonary valves, who met retrieval criteria, morphological assessment was done.
      69.5% of aortic and 37.5% of pulmonary valves were considered unsuitable for
      transplantation at morphological assessment. Backward stepwise multivariate
      logistic regression analysis, showed age, cardiac cause of death, cerebrovascular
      accident as cause of death or in medical history, and number of cardiovascular
      risk factors in a donor to be independent risk factors for morphological
      rejection of aortic valves. Age, sex, weight >100 kg and ruptured aortic aneurysm
      as cause of death were independent risk factors for morphological rejection of
      pulmonary valves. Being an organ donor was an independent predictor of
      morphological approval of aortic and pulmonary valves, while hypertension was an
      independent predictor for morphological approval of aortic valves. Thus,
      independent factors were identified that are associated with morphological
      rejection of aortic and pulmonary valves for transplantation, and that could be
      used to optimize donor selection by preventing unnecessary retrievals, limiting
      costs, while improving yield per donor with minimal compromise for availability.

PMID- 21744231
TI  - The growth hormone receptor polymorphism in patients with acromegaly:
      relationship to BMI and glucose metabolism.
AB  - The aim of this study was to investigate association between the frequencies of
      Growth Hormone receptor (d3GHR) gene polymorphisms and some clinical parameters
      of acromegalic patients. Total of 35 acromegalic patients were enrolled to study.
      The d3GHR polymorphism was identified by using polymerase chain reaction from
      peripheral blood samples. The levels of systolic and diastolic blood pressure,
      BMI, fasting plasma glucose (FPG), Fasting insulin, HOMA-IR, IGF-I, GH, IGFBP3,
      triglyceride, HDL and LDL cholesterol concentrations were evaluated. The
      frequencies of d3GHR genotypes were found as follows; 5 (14.3%) subjects had
      d3/d3, 11 (31.4%) had d3/fl and 19 (54.3%) had fl/fl in patients. The prevalence
      of the d3 and fl alleles was 30 and 70%, respectively. Systolic blood pressure,
      fasting insulin and HOMA-IR was found significantly increased in homozygote d3GHR
      genotype group compared to d3/fl subjects (P < 0.05). In addition, BMI was
      observed significantly different among three genotypes (P = 0.007) and in the
      subjects with d3/d3 genotype, BMI was found significantly higher than d3/fl and
      fl/fl genotypes groups. As well as, no significant difference was found between
      the d3 and fl alleles group in terms of the clinical parameters except for BMI (P
      = 0.002). It can be said that the d3GHR gene polymorphism may affect BMI,
      systolic blood pressure and insulin regulation. At the same time we can say
      homozygote d3GHR genotype and d3 allele carriers may have more risk than other
      genotypes for high BMI.

PMID- 21744232
TI  - MR spectroscopy as a tool for in vivo determination of steatosis in liver
      transplant recipients.
AB  - OBJECT: Among several non-invasive methods of liver fat analysis, the most
      important role is played by MR imaging and spectroscopy (MRS). This study
      describes the 1H MRS at 3T measurement of liver fat volume fraction Phi(fat) in a
      group of liver transplant patients, an at-risk group for the development of de
      novo steatosis. MATERIALS AND METHODS: Seventy-seven liver transplant recipients
      who underwent routine protocolar posttransplant examination were divided into
      three groups: CON-PAT (control group for the cross validation test, 48 patients),
      PAT-PAT (patients test group for the cross validation test, 29 patients), and PAT
      (pooled data). Single voxel 1H MRS at 3T was used for the determination of
      Phi(fat) and histology results (His) were used as the reference standard.
      RESULTS: Linear and non-linear regression models were used to describe the
      relationship between Phi(fat) and His. Strong correlation was found for both
      models with r = 0.83-0.94 (P < 0.001); a higher r was found for non-linear
      regression in all tested groups. Areas under receiver operation curves were
      calculated for cut points His >= 5 and > 33% and were found in the range of 0.77
      0.86. Fibrosis influences the calculation of Phi(fat) and different slopes were
      obtained for fibrosis stages F0-F1 and F2-F3, respectively. CONCLUSION:
      Significant correlation was found between the results of histology and 1H MRS
      measurement of liver fat content. The method is suitable for non-invasive
      repetitive examination of liver fat in liver-transplants patients between
      protocol biopsies and for the screening of steatosis in other liver diseases.

PMID- 21744233
TI  - Is snoring intensity responsible for the sleep partner's poor quality of sleep?
AB  - PURPOSE: This study aimed to determine if the intensity of breathing noise
      (including snoring) and/or the presence of abnormal breathing events (ABE) are
      factors that trigger arousal/awakening of a snorer's bed partner. METHODS: We
      conducted a prospective multicenter study investigating couples where the male
      had a chronic disturbing snoring. We simultaneously recorded the male's
      respiration and snoring and the female' sleep. We counted the number of arousals
      and awakenings during N2 sleep and randomly took nine of each. Then, for periods
      before, during, and after each arousal and awakening, we observed on the
      respiratory tracings what was happening in terms of breathing noise intensity and
      presence/absence of snoring and/or ABE. RESULTS: Thirteen couples were analyzed.
      The intensity of breathing noise and the presence/absence of snoring and/or ABE
      were comparable before and at initiation of arousal/awakening and between arousal
      and awakening. However, breathing volume intensity was lower and the presence of
      snoring and/or ABE was less frequent when the bed partner returned back to sleep
      from awakening compared to the other periods (p always <0.001). CONCLUSIONS: The
      intensity of breathing noise or the presence of ABE does not seem to be essential
      to trigger an arousal or an awakening. However, the persistence of noise or
      events may prolong the duration of wakefulness during the sleep period and could
      be one factor that explains the bothersome snoring.

PMID- 21744234
TI  - Internal fixation of dorsally comminuted fractures of the distal part of the
      radius: a biomechanical analysis of volar plate and intramedullary nail fracture
      stability.
AB  - INTRODUCTION: The purpose of the present study was to carry out biomechanical
      testing of "new generation" volar plates and an intramedullary nail. METHODS:
      Four volar locking plates (Column Plate, VariAx distal radius, 2.4 mm-LCP and 3.5
      mm-LCP) and the intramedullary nail, Targon-DR, were implanted in biomechanically
      validated artificial bones after simulation of a wedge osteotomy with total
      transection of the volar cortex to mimic a type 23 A3-fracture according to the
      AO-classification. Axial load (250 Newton [N]) and volar and dorsal bending loads
      (both 50 N) were applied. Axial load was increased to fixation failure. Gap
      motion was measured three-dimensionally directly at the fracture gap. The 3.5 mm
      LCP was used for comparison as it currently represents an established locking
      implant that has been well tested biomechanically. RESULTS: In this experimental
      setting, the 2.4 mm-LCP showed the lowest resistance under all three loading modi
      and, consequently, the highest level of motion at the osteotomy gap in comparison
      to all other implants (p < 0.05). Under axial loading, there were no significant
      differences between the other four implants. Under dorsal bending, the Targon-DR
      nail and the VariAx-plate showed less gap displacement in comparison to the 3.5
      mm-LCP (p < 0.05). Under volar bending, only the Targon-nail showed greater
      resistance than the 3.5 mm-LCP (p < 0.05) with no other significant differences
      between the Column Plate, the VariAx and the 3.5 mm-LCP. CONCLUSION: In this
      experimental setting, all "new generation" implants for distal radius fractures
      with the exception of the 2.4 mm-LCP showed identical or higher stability
      compared to the 3.5 mm-LCP. The 2.4 mm-LCP showed the lowest resistance and this
      must be taken into consideration when planning postoperative functional therapy.

PMID- 21744235
TI  - Application of ethyl chloroformate derivatization for solid-phase microextraction
      gas chromatography-mass spectrometric determination of bisphenol-A in water and
      milk samples.
AB  - A simple and rapid analytical method based on in-matrix ethyl chloroformate (ECF)
      derivatization has been developed for the quantitative determination of bisphenol
      A (BPA) in milk and water samples. The samples containing BPA were derivatised
      with ECF in the presence of pyridine for 20 s at room temperature, and the non
      polar derivative thus formed was extracted using polydimethylsiloxane solid-phase
      microextraction (SPME) fibres with thicknesses of 100 MUm followed by analysis
      using gas chromatography-mass spectrometry. Three alkyl chloroformates (methyl,
      ethyl and isobutyl chloroformate) were tested for optimum derivatisation yields,
      and ECF has been found to be optimum for the derivatisation of BPA. Several
      parameters such as amount of ECF, pyridine and reaction time as well as SPME
      parameters were studied and optimised in the present work. The limit of detection
      for BPA in milk and water samples was found to be 0.1 and 0.01 MUg L(-1),
      respectively, with a signal-to-noise ratio of 3:1. The limit of quantitation for
      BPA in milk and water was found to be 0.38 and 0.052 MUg L(-1), respectively,
      with a signal-to-noise ratio of 10:1. In conclusion, the method developed was
      found to be rapid, reliable and cost-effective in comparison to silylation and
      highly suitable for the routine analysis of BPA by various food and environmental
      laboratories.

PMID- 21744236
TI  - Raman detection of localized transferrin-coated gold nanoparticles inside a
      single cell.
AB  - We investigated the cellular uptake behavior of non-fluorescent metal
      nanoparticles (NPs) by use of surface-enhanced Raman scattering (SERS) combined
      with dark-field microscopy (DFM). The uptake of Au NPs inside a single cell could
      also be identified by DFM first and then confirmed by z-depth-dependent SERS at
      micrometer resolution. Guided by DFM for the location of Au NPs, an intracellular
      distribution assay was possible using Raman dyes with unique vibrational marker
      bands in order to identify the three-dimensional location inside the single cell
      by obtaining specific spectral features. Au NPs modified by 4-mercaptobenzoic
      acid (MBA) bearing its -COOH surface functional group were used to conjugate
      transferrin (Tf) protein using the 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide
      hydrochloride (EDC) reaction. The protein conjugation reaction on Au surfaces was
      examined by means of color change, absorption spectroscopy, and SERS. Our results
      demonstrate that DFM techniques combined with SERS may have great potential for
      monitoring biological processes with protein conjugation at the single-cell
      level.

PMID- 21744237
TI  - Catanionic surfactant ambient cloud point extraction and high-performance liquid
      chromatography for simultaneous analysis of organophosphorus pesticide residues
      in water and fruit juice samples.
AB  - A mixed anionic-cationic surfactant cloud point extraction (CPE) has been
      developed using sodium dodecyl sulfate (SDS) and tetrabutylammonium bromide
      (TBABr) for the extraction and preconcentration of organophosphorus pesticides
      (OPPs) at ambient temperature before analysis by high-performance liquid
      chromatography. The studied OPPs were azinphos-methyl, parathion-methyl,
      fenitrothion, diazinon, chlorpyrifos, and prothiophos. The optimum conditions of
      the mixed anionic-cationic CPE were 50 mmol L(-1) SDS, 100 mmol L(-1) TBABr, and
      10% (w/v) NaCl. The extracted OPPs were successfully separated within 11 min
      using the conditions of a Waters Symmetry C8 column, a flow rate of 0.8 mL min(
      1), a gradient elution of methanol and water, and detection at 210 nm. Linearity
      was found over the range 0.05-5 MUg mL(-1), with the correlation coefficients
      higher than 0.996. The enrichment factor of the target analytes was in the range
      6-11, which corresponds to their limits of detection from 1 to 30 ng mL(-1). High
      precisions (intra-day and inter-day) were obtained with relative standard
      deviation <1.5% (t(R)) and 10% (peak area). Accuracies (% recovery) of the
      different spiked OPP concentrations were 82.7-109.1% (water samples) and 80.3
      113.3% (fruit juice samples). No contamination by the OPPs was observed in any
      studied samples.

PMID- 21744238
TI  - Standardization of activated sludge for biodegradation tests.
AB  - Activated sludges are an inoculum source commonly used in biodegradation studies,
      as wastewater treatment facilities constitute an entry point to the environment
      for many chemicals. In this paper, the main issues relating to the use of
      activated sludge in biodegradability tests are presented. Special attention is
      also devoted to discussing the factors affecting both the activity of the
      microbial communities and the test results. After a short survey of the state of
      the art of microbiology of activated sludge, the paper focuses on the methods
      used to reduce the variations in the diversity, quality and quantity of these
      communities. Finally, use of surrogates as reference materials in
      biodegradability tests is discussed.

PMID- 21744239
TI  - LC-ESI/MS/MS method for rapid screening and confirmation of 44 exogenous anabolic
      steroids in human urine.
AB  - A sensitive and rapid method based on liquid chromatography-triple-quadrupole
      tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI) has been
      developed and validated for the screening and confirmation of 44 exogenous
      anabolic steroids (29 parent steroids and 15 metabolites) in human urine. The
      method involves an enzymatic hydrolysis, liquid-liquid extraction, and detection
      by LC-MS/MS. A triple-quadrupole mass spectrometer was operated in positive ESI
      mode with selected reaction monitoring (SRM) mode for the screening and product
      ion scan mode for the confirmation. The protonated molecular ions were used as
      precursor ions for the SRM analysis and product ion scan. The intraday and
      interday precisions of the target analytes at concentrations of the minimum
      required performance levels for the screening were 2-14% and 2-15%, respectively.
      The limits of detection for the screening and confirmation method were 0.1-10
      ng/mL and 0.2-10 ng/mL, respectively, for 44 steroids. This method was
      successfully applied to analysis of urine samples from suspected anabolic steroid
      abusers.

PMID- 21744240
TI  - A toast to wine analysis.

PMID- 21744241
TI  - Are symptomatic guidelines for chemotherapy appropriate to ER-positive screen
      detected breast cancer (SDBC)?
AB  - Oncologists recommend chemotherapy to postmenopausal women with adverse
      prognostic factors, but predictors of the benefit of chemotherapy are mainly
      based on mortality from symptomatic cancer trials. From 1990 to 1998, 1475 breast
      cancers (875 screen detected cancers [SDBCs]: 600 symptomatic) were treated in
      women aged 50-65 years and prognostic factors compared with cancer mortality.
      Median follow-up was 110 months. The Nottingham Prognostic Index (NPI) was
      calculated for 6737 breast cancers which were part of the Association of Breast
      Surgery (ABS) 2001/2002 Audit of SDBCs to validate survival figures. Ten year
      survival was 92.1% for SDBC and 77.6% for symptomatic cancers. Adjusting for
      baseline factors, SDBCs had a reduced mortality (RR = 0.42 (0.31-0.57),
      independent of grade, node status and tumour size. Oestrogen receptor (ER)
      positive SDBC had a lower annual mortality rate (0.6%) compared with symptomatic
      (4.3%: P < 0.001) or ER negative SDBC (1.8%). Epithelial proliferation was lower
      in SDBC in all NPI groups compared with symptomatic cancers (P <= 0.001). Grade,
      node status, ER status, size and mode of detection predicted survival. Survival
      for each NPI group was better for SDBC. For ER positive SDBC in the Moderate
      Prognostic Group 1 (MPG1), 10 year mortality was 6.4% compared with 17.6% in
      symptomatic (P = 0.001). NPI on 6,737 operable SDBC confirmed similar mortality
      in all groups (4% mortality in MPG1 group). SDBC have lower mortality than
      symptomatic due to a lower proliferative index. The use of adjuvant chemotherapy
      is over-treatment for ER positive SDBCs with Good Prognostic Group (GPG) and MPG1
      NPI scores.

PMID- 21744242
TI  - The neuroprotective effect of two statins: simvastatin and pravastatin on a
      streptozotocin-induced model of Alzheimer's disease in rats.
AB  - Astrocytes play a fundamental role in glutamate metabolism by regulating the
      extracellular levels of glutamate and intracellular levels of glutamine. They
      also participate in antioxidant defenses, due to the synthesis of glutathione,
      coupled to glutamate metabolism. Although the cause of Alzheimer's disease (AD)
      remains elusive, some changes in neurochemical parameters, such as glutamate
      uptake, glutamine synthetase activity and glutathione have been investigated in
      this disease. A possible neuroprotective effect of two statins, simvastatin and
      pravastatin (administered p.o.), was evaluated using a model of dementia, based
      on the intracerebroventricular (ICV) administration of streptozotocin (STZ), and
      astrocyte parameters were determined. We confirmed a cognitive deficit in rats
      submitted to ICV-STZ, and a prevention of this deficit by statin administration.
      Moreover, both statins were able to prevent the decrease in glutathione content
      and glutamine synthetase activity in this model of AD. Interestingly, simvastatin
      increased per se glutamate uptake activity, while both statins increased
      glutamine synthetase activity per se. These results support the idea that these
      drugs could be effective for the prevention of alterations observed in the STZ
      dementia model and may contribute to reduce the cognitive impairment and brain
      damage observed in AD patients.

PMID- 21744243
TI  - Do small headgroups of phosphatidylethanolamine and phosphatidic acid lead to a
      similar folding pattern of the K(+) channel?
AB  - Phospholipid headgroups act as major determinants in proper folding of oligomeric
      membrane proteins. The K(+)-channel KcsA is the most popular model protein among
      these complexes. The presence of zwitterionic nonbilayer lipid
      phosphatidylethanolamine (PE) is crucial for efficient tetramerization and
      stabilization of KcsA in a lipid bilayer. In this study, the influence of PE on
      KcsA folding properties was analyzed by tryptophan fluorescence and acrylamide
      quenching experiments and compared with the effect of anionic phosphatidic acid
      (PA). The preliminary studies suggest that the small size and hydrogen bonding
      capability of the PE headgroup influences KcsA folding via a mechanism quite
      similar to that observed for anionic PA.

PMID- 21744244
TI  - A Hessian-based filter for vascular segmentation of noisy hepatic CT scans.
AB  - PURPOSE: Extraction and enhancement of tubular structures are important in image
      processing applications, especially in the analysis of liver CT scans where
      delineation of vascular structures is needed for surgical planning. Portal vein
      cross-sections have circular or elliptical shapes, so an algorithm must
      accommodate both. A vessel segmentation method based on medial-axis points was
      developed and tested on portal veins in CT images. METHODS: A medial-axis
      enhancement filter was developed. Consider a line passing through a point inside
      a tube and intersecting the edges of the tube. If the point is located on the
      medial axis, the distance of the point in the direction of the line to the edges
      of the tube will be equal. This feature was employed in a multi-scale framework
      to identify liver vessels. Dynamic thresholding was used to reduce noise
      sensitivity. The isotropic coefficient introduced by Pock et al. was used to
      reduce the response of the filter for asymmetric cross-sections. RESULTS:
      Quantitative and qualitative evaluation of the proposed method were performed
      using both 2D/3D and synthetic/clinical datasets. Compared to other methods for
      medial-axis enhancement, our method produces better results in low-resolution CT
      images. Detection rate of the medial axis by the proposed method in a noisy image
      of standard deviation equal to 0.3 is 68% higher than prior methods. CONCLUSION:
      A new Hessian-based method for medial axis vessel segmentation was developed and
      tested. This method produced superior results compared to prior methods. This new
      method has the potential for many applications of medial-axis enhancement.

PMID- 21744245
TI  - Alcohol use among Latinos: a comparison of pre-immigration, post-immigration, and
      US born Latinos.
AB  - US born Latinos have higher rates of alcohol use than Latino immigrants. Yet,
      little is known about drinking patterns of Latinos before their immigration to
      the US This exploratory study compares the past month regular, binge, and heavy
      alcohol use patterns of Latino immigrants prior to immigration with that of post
      immigration and US born Latinos. Data on past month alcohol use prior to
      immigration was collected from 516 recent adult Latino immigrants. Results were
      compared with US born and post-immigration Latinos using national aggregate data.
      Alcohol use patterns among Latino immigrants prior to immigration were similar to
      that of US born Latinos. Alcohol use patterns were lower among Latinos after
      immigration when compared to pre-immigration and US born Latinos. This study
      provides a foundation for further exploration of the drinking patterns of Latinos
      in the US before they immigrated to this country. Findings suggest more research
      is needed to uncover the underlying factors associated with the higher rates of
      alcohol use among Latinos prior to their immigration when compared to alcohol use
      patterns of post-immigration Latinos.

PMID- 21744246
TI  - Image quality and radiation dose comparison of prospectively triggered low-dose
      CCTA: 128-slice dual-source high-pitch spiral versus 64-slice single-source
      sequential acquisition.
AB  - Currently 64-multislice computed tomography (MSCT) scanners are the most widely
      used devices allowing low radiation dose coronary CT angiography (CCTA) with
      prospective ECG triggering. Latest 128-slice dual-source CT (DSCT) scanners offer
      prospective high-pitch spiral acquisition covering the heart during one single
      beat. We compared radiation dose and image quality from prospective 64-MSCT
      versus high-pitch spiral 128-slice DSCT scanning, as such data is lacking. CCTA
      of 50 consecutive patients undergoing 128-DSCT (2 * 64 * 0.6 mm collimation, 0.28
      s rotation time, 3.4 pitch, 100-120 kV tube voltage and 320 mAs tube current-time
      product) were compared to CCTA of 50 heart rate (HR) and BMI matched patients
      undergoing 64-MSCT (64 * 0.625 mm collimation, 0.35 s rotation time, 100-120 kV
      tube voltage and 400-650 mA tube current). Image quality was rated on a 4-point
      scale by two independent cardiac imaging physicians (1 = excellent to 4 = non
      diagnostic). Of 710 coronary segments assessed on 128-DSCT, 216 (30.4%) achieved
      an image quality score 1 excellent, 400 (56.3%) score 2, 76 (10.7%) score 3 and
      18 (2.6%) score 4 (non-diagnostic). Of 737 coronary segments evaluated on 64-MSCT
      271 (36.8%) had an image quality score of 1, 327 (44.4%) 2, 110 (14.9%) score 3,
      and 29 (3.9%) segments score 4. Average image quality score for both scanners was
      similar (P = 0.641). The mean heart rate during scanning was 58.7 +/- 5.6 bpm on
      128-DSCT and 59.0 +/- 5.6 bpm on 64-MSCT, respectively. Mean effective radiation
      dose was 1.0 +/- 0.2 mSv for 128-DSCT and 1.7 +/- 0.6 mSv for 64-MSCT (P <
      0.001). 128-DSCT with high-pitch spiral mode allows CCTA acquisition with reduced
      radiation dose at maintained image quality compared to 64-MSCT.

PMID- 21744248
TI  - Comparison between 2D and 3D computed tomography evaluation of glenoid bone
      defect in unilateral anterior gleno-humeral instability.
AB  - PURPOSE: This study evaluated the agreement between 2D and 3D computed tomography
      (CT) measurements in identifying the size and type of glenoid-bone defect in
      anterior glenohumeral instability. MATERIALS AND METHODS: One hundred patients
      affected by unilateral anterior glenohumeral instability underwent a CT of both
      shoulders. Images were processed with both 2D [multiplanar reconstruction (MPR)]
      and 3D [volumerendering (VR)] methods. The area of the missing glenoid was
      calculated in comparison with the healthy glenoid and expressed as a percentage.
      Agreement between the two measurements was assessed according to the Bland-Altman
      method; a 5% mean difference was considered as clinically relevant. RESULTS:
      Analysis of agreement between MPR and VR measurements of the percentage of
      missing glenoid showed a mean difference equal to 0.62%+/-1.96%. Percent
      agreement between the two measurements in detecting the presence of bone defect
      was 97% (p<0.0001). Percent agreement between the two measurements in
      discriminating the type of bone defect was 97% (p<0.0001). CONCLUSIONS: Agreement
      between 2D (MPR) and 3D (VR) CT measurements to identify the size and type of
      glenoid-bone defect in anterior glenohumeral instability was so high that the two
      measurements can be considered interchangeable.

PMID- 21744247
TI  - Matrix metalloproteinases in tumorigenesis: an evolving paradigm.
AB  - Proteases are crucial for development, tissue remodeling, and tumorigenesis.
      Matrix metalloproteinases (MMPs) family, in particular, consists of more than 20
      members with unique substrates and diverse function. The expression and activity
      of MMPs in a variety of human cancers have been intensively studied. MMPs have
      well-recognized roles in the late stage of tumor progression, invasion, and
      metastasis. However, increasing evidence demonstrates that MMPs are involved
      earlier in tumorigenesis, e.g., in malignant transformation, angiogenesis, and
      tumor growth both at the primary and metastatic sites. Recent studies also
      suggest that MMPs play complex roles in tumor progression. While most MMPs
      promote tumor progression, some of them may protect the host against
      tumorigenesis in a context-dependent manner. MMPs have been chosen as promising
      targets for cancer therapy on the basis of their aberrant up-regulation in
      malignant tumors and their ability to promote cancer metastasis. Although
      preclinical studies testing the efficacy of MMP suppression in tumor models were
      so encouraging, the results of clinical trials in cancer patients have been
      rather disappointing. Here, we review the complex roles of MMPs and their
      endogenous inhibitors such as tissue inhibitors of metalloproteinase in
      tumorigenesis and strategies in suppressing MMPs.

PMID- 21744249
TI  - Analysis of proportional incidence and review of interval cancer cases observed
      within the mammography screening programme in Trento province, Italy.
AB  - PURPOSE: The aim of this study was to assess the performance of the mammography
      screening programme in Trento Province, Italy, by analysing the interval cancers
      (IC) observed from 2001 to 2008. MATERIAL AND METHODS: IC were identified by
      linking screening archives with local cancer registry and pathology archives as
      well as with hospital discharge records. Proportional incidence was determined
      according to breast cancers expected in the absence of screening, estimated on
      the basis of patients/year at risk and age-specific incidence. The review of
      screening mammograms preceding ICs was performed by an external (three
      radiologists) and an internal (five radiologists) panel and aimed at assessing
      the proportion of IC reviewed as screening errors. Results were compared with
      European Community (EC) recommended standards. RESULTS: IC proportional incidence
      was 15.90% for the first year (EC standard <30%) and 25.77% for the second year
      (EC standard <50%) of the interval. At external review, 18.4% of cases were
      reviewed as screening errors (identified by at least two of three reviewers),
      whereas at internal review (identified by at least three of five reviewers) it
      was 17.4% (EC standard <20%). No significant difference was observed between
      external and internal review (mean recall rate 8.3% vs. 9.0%; mean identification
      rate 19.7% vs 19.6%). CONCLUSIONS: The study confirms good performance of the
      mammography screening programme in Trento Province, Italy. Comparable results of
      external and internal reviews suggest that the latter, no doubt easier to be
      implemented, might be adopted as a routine procedure to assess this early
      efficacy indicator.

PMID- 21744250
TI  - Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing
      cardiac effects of long-term enzyme replacement therapy.
AB  - PURPOSE: Anderson-Fabry disease is a multisystemic disorder of lipid metabolism
      secondary to X-chromosome alterations and is frequently associated with cardiac
      manifestations such as left ventricular (LV) hypertrophy, gradually leading to an
      alteration in cardiac performance. The purpose of this study was to monitor,
      using magnetic resonance imaging (MRI), any changes produced by enzyme
      replacement therapy with agalsidase beta at the cardiac level in patients with
      Anderson-Fabry disease. MATERIALS AND METHODS: Sixteen (ten men, six women)
      patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI
      before starting enzyme replacement therapy (baseline study) and after 48 months
      of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study).
      RESULTS: After 48 months of treatment, a significant reduction in LV mass and
      wall thickness was observed: 187+/-59 g vs. 149+/-44 g, and 16+/-3 mm vs. 13+/-3
      mm, respectively. A significant reduction in T2 relaxation time was noted at the
      level of the interventricular septum (81+/-3 ms vs. 67+/-7 ms), at the apical
      level (80+/-8 ms vs. 63+/-6 ms) and at the level of the lateral wall (82+/-8 ms
      vs. 63+/-10 ms) (p<0.05). No significant variation was observed in ejection
      fraction between the two studies (65+/-3% vs. 64+/-2%; p>0.05) (mean bias 1.0);
      however, an improvement was noted in the New York Heart Association (NYHA) class
      of the majority of patients (12/16) (p<0.05). CONCLUSIONS: In patients with
      Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase
      beta, MRI documented a significant reduction in myocardial T2 relaxation time, a
      significant decrease in maximal myocardial thickness and in total LV mass. MRI
      did not reveal significant improvements in LV global systolic function; however,
      improvement in NYHA functional class was noted, consistent with improved
      diastolic function.

PMID- 21744251
TI  - Assessment of soft tissue tumours of the extremities with diffusion echoplanar MR
      imaging.
AB  - PURPOSE: This study assessed soft tissue tumours of the extremities with
      diffusion echo-planar magnetic resonance (MR) imaging. MATERIALS AND METHODS: We
      carried out a retrospective study of 37 patients (22 male, 15 female; age range 4
      68 years; mean age 41 years) with a soft tissue mass. Diffusion-weighted magnetic
      resonance (MR) imaging was done using echo-planar imaging (EPI) with b factor of
      0.500 and 1,000 mm2/s. The apparent diffusion coefficient (ADC) map was
      reconstructed with calculation of the ADC values of the mass. RESULTS: The mean
      ADC value of the malignant tumours was 1.02+/-0.03*10(-3)mm(2)/s and that of
      benign masses 1.54+/-0.03*10(-3)mm(2)/s. There was a significant difference in
      the ADC values between malignant soft tissue tumours and benign masses (p<0.001)
      and within different grades of malignancy (p<0.02). Selection of 1.34*10(-3)
      mm(2)/s as a threshold ADC value for differentiating malignant soft tissue
      tumours from benign masses resulted in an accuracy of 91%, sensitivity of 94%,
      specificity of 88% and area under the curve of 0.869. There was a significant
      difference in the ADC value between well- and poorly differentiated malignancies
      (p=0.001). CONCLUSIONS: Diffusion-weighted echo-planar MR imaging is a promising
      noninvasive modality that may be helpful in differentiating malignant soft tissue
      tumours from benign masses as well as in grading malignancy.

PMID- 21744252
TI  - Whole-body MR-DWIBS vs. [18F]-FDG-PET/CT in the study of malignant tumors: a
      retrospective study.
AB  - PURPOSE: Our aim was to assess the overall diagnostic accuracy of magnetic
      resonance diffusion-weighted whole-body imaging with background signal
      suppression (MR-DWIBS) compared with ([(18)F]-fluorodeoxyglucose (FDG)-positron
      emission tomography (PET)/computed tomography (CT), considered the reference
      standard of whole-body tumour imaging modalities, in a series of consecutive
      patients with malignant tumour. MATERIALS AND METHODS: Thirty-eight patients
      diagnosed with a malignant tumour over a 4-month period were enrolled in this
      retrospective, observational study. PET/CT and MR-DWIBS images were reviewed in
      double-blind manner by a nuclear medicine physician and radiologists with 4 years
      experience. Lesion size, standard uptake value (SUV) and apparent diffusion
      coefficient (ADC) were measured and calculated for each lesion. RESULTS: The
      qualitative analysis of MR-DWIBS and [(18)F]-FDG-PET/CT showed that two patients
      were negative at both techniques. MR-DWIBS was positive in 36 patients, 34 of
      whom were positive and two negative at [(18)F]-FDG-PET/CT, respectively. Two
      hundred and fifty-five lesions were identified by MR-DWIBS and 184 by [(18)F]-FDG
      PET/CT, which was a significative discordance. Correlation between SUV and ADC of
      lesions positive at both techniques was not statistically significant. The mean
      difference between lesion size in [(18)F]-FDG-PET/CT and MR-DWIBS was not
      statistically significant. No correlation was found between glucose metabolism
      and water motion. CONCLUSIONS: MR-DWIBS may be used to evaluate localisation of
      parenchymal neoplasms but is less efficacious in characterising lymph-node and
      skeletal lesions. [(18)F]-FDG-PET/CT remains the best whole-body technique to
      identify lymph-node and skeletal lesions, but its limitation is identifying
      tumours with low glucose metabolism as in mucinous neoplasms. MR-DWIBS evaluation
      must be integrated with morphological images to increase MR diagnostic accuracy.

PMID- 21744253
TI  - Impact of magnetic resonance cholangiography in managing liver-transplanted
      patients: preliminary results of a clinical decision-making study.
AB  - PURPOSE: This study was performed to assess the role of magnetic resonance
      cholangiography (MRC) in the clinical decision-making process of referring
      physicians when managing liver-transplanted patients. MATERIALS AND METHODS: Over
      a 6-month period, 21 liver-transplanted patients with a suspected biliary
      complication were referred for MRC. Referring physicians were asked to
      prospectively state, before and after MRC, the leading diagnosis; the level of
      confidence (on a 0-100% scale); the most appropriate diagnostic/therapeutic plan.
      Data analysis assessed was the diagnostic yield of MRC; the proportion of change
      in the leading diagnosis; the therapeutic efficacy (i.e. proportion of change in
      the initial diagnostic/therapeutic plan); the diagnostic thinking efficacy (i.e.,
      gain in diagnostic confidence). Statistical significance was assessed with the
      Mann-Whitney U test. MRC accuracy was also calculated. RESULTS: Data analysis
      showed a diagnostic yield of 85.7%; a proportion of change in leading diagnosis
      of 19.0%; a therapeutic efficacy of 42.8%; a diagnostic thinking efficacy for
      concordant and discordant leading diagnoses of 18.8% and 78.7%, respectively
      (p<0.01). MRC accuracy was 92.3%. CONCLUSIONS: MRC significantly increased the
      diagnostic confidence, irrespective of the concordance between pre- and posttest
      diagnoses. Moreover, MRC determined a change in patient management in a
      significant proportion of cases, leading to clinical benefits.

PMID- 21744254
TI  - Magnetic resonance imaging of painful total hip replacement: detection and
      characterisation of periprosthetic fluid collection and interobserver
      reproducibility.
AB  - PURPOSE: The purpose of our study was to demonstrate the diagnostic value of
      magnetic resonance imaging (MRI) when measuring and characterising periprosthetic
      fluid collections in patients with painful hip prosthesis and to provide an
      estimation of interobserver reproducibility. MATERIALS AND METHODS: Nineteen
      patients (mean age 59+/-13 years) with painful total hip replacement and clinical
      suspicion of infection underwent MRI. Images were reviewed blindly by two
      musculoskeletal radiologists with different levels of experience who evaluated
      the presence/absence of soft tissue oedema or fluid collection (when present,
      three-plane maximal diameters were measured; involvement of
      skin/subcutaneous/deep tissues or prosthesis were estimated; fluid was classified
      as serous/purulent/haematic according to signal behaviour). Interobserver
      agreement was calculated (Cohen's ). RESULTS: A total of 26 MRI studies were
      carried out (three patients underwent two and two patients underwent three MRI
      examinations). Both readers detected soft tissue oedema (13/26, 50%) or fluid
      collection (21/26, 81%) and characterised the fluid as serous (9/21, 43%),
      purulent (8/21, 38%) or haematic (4/21, 19%). The collection involved
      skin/subcutaneous tissues (16/21, 76%), deep soft tissues (19/21, 91%) or the
      implant (12/21, 57%). For all evaluations, interobserver agreement was complete
      (=1). No significant differences were found between the measurements of the
      collections (p>0.258). CONCLUSIONS: MRI is highly reproducible in detection,
      localisation, quantification, and characterisation of fluid collections when the
      presence of implant infection is clinically suspected.

PMID- 21744255
TI  - The radiological report... and then what?
AB  - The radiology report has always been considered as "the most important step in
      the clinical radiological act". While agreeing with this concept, the author
      emphasises that the report can in no way replace the duty to communicate with the
      patient, as mentioned in Art. 31, Italian Code of Medical Ethics. Italy aside,
      this issue has been thoroughly investigated and debated abroad since the 1970s
      and, in the past as well as more recently, many interesting contributions have
      been published both on the need for verbal communication, particularly in certain
      settings, and on the best manner to approach this task. A recent book published
      in Italy also provides useful advice in this regard. The author hopes that in
      Italy, as in other countries, an extensive debate will give rise to a fuller
      awareness of the issue, thereby providing a range of shared solutions.

PMID- 21744256
TI  - Multifocal, multicentric and contralateral breast cancers: breast MR imaging in
      the preoperative evaluation of patients with newly diagnosed breast cancer.
AB  - PURPOSE: This study was done to verify the usefulness of preoperative breast
      magnetic resonance (MR) imaging in patients with newly diagnosed breast cancer.
      MATERIALS AND METHODS: A retrospective analysis of 291 patients with invasive
      breast cancer newly diagnosed with conventional breast imaging (mammography and
      ultrasound) was performed. All patients underwent MR imaging prior to surgery.
      The MR imaging detection rate of additional malignant cancers occult to
      mammography and ultrasound was calculated. Data were analysed with Fisher's exact
      test (p<0.05) according to the following parameters: histopathological features
      of the index tumour (histological type and size) and mammographic density
      [according to the Breast Imaging Reporting and Data System (BI-RADS)
      classification from 1 fatty to 4 dense). The gold standard was the histological
      examination on the surgical specimen. RESULTS: MR imaging identified 40
      mammographically and sonographically occult malignant lesions other than the
      index cancer in 27/291 patients (9%). These additional cancers were located in
      the same quadrant as the index cancer in 13 women (4%), in a different quadrant
      in 12 (4%) and in the contralateral breast in the remaining two (1%). The cancer
      detection rate in the subgroup of index cancers with lobular histological type
      was 25%, significantly higher (p=0.03) than the detection rate of 11% recorded in
      the subgroup of ductal cancers. The cancer detection rate in the subgroup of
      index cancers >2 cm was 27%, significantly higher (p=0.001) than the rate of 8%
      found in the subgroup of index cancers <2 cm. Mammographic density was not
      correlated (p=0.48) with MR detection of additional cancer, with 14% of
      additional malignancies being detected in both dense and fatty breasts.
      CONCLUSIONS: In patients with newly diagnosed invasive breast cancer,
      preoperative MR imaging is useful for detecting additional synchronous
      malignancies that are not detected on conventional breast imaging. The cancer
      detection rate is 9%. The use of preoperative MR imaging as an adjunct to
      conventional breast imaging in women with an infiltrating lobular index cancer
      and an index cancer >2 cm is especially beneficial.

PMID- 21744257
TI  - Hepatocyte growth factor upregulation promotes carcinogenesis and epithelial
      mesenchymal transition in hepatocellular carcinoma via Akt and COX-2 pathways.
AB  - Advanced hepatocellular carcinoma (HCC) is an important cause of cancer
      mortality. Epithelial-mesenchymal transition (EMT) has been shown to be an
      important biological process in cancer progression and metastasis. We have
      focused on elucidating factors that induce EMT to promote carcinogenesis and
      subsequent metastasis in HCC using the BNL CL.2 (BNL) and BNL 1ME A. 7R.1 (1MEA)
      cell lines. BNL cells are normal hepatocytes whereas the 1MEA cells are HCC cells
      derived from chemical transformation of the BNL cells. Their morphological
      characteristics were examined. Expression levels of hepatocyte growth factor
      (HGF), markers of EMT and mediators of HGF signaling were determined and
      functional characteristics were compared. BNL cells were treated with HGF and
      effects on EMT-marker and mediators of HGF signaling were analyzed. BNL cells
      display characteristic epithelial morphology whereas 1MEA cells display
      mesenchymal characteristics. 1MEA cells express and secrete more HGF than BNL
      cells. There was significantly decreased expression of E-cadherin, albumin, AAT
      and increased expression of fibronectin, collagen-1, vimentin, snail and slug in
      1MEA cells. There was also increased expression of cyclooxygenase-2 (COX-2), Akt
      and phosphorylated Akt (pAkt) in 1MEA cells. Moreover, 1MEA cells had increased
      migratory capacity inhibited by inhibition of COX-2 and Akt but not extracellular
      signal regulated kinase (ERK). Molecular mesenchymal characteristics of 1MEA
      cells were reversed by inhibition of COX-2, Akt and ERK. Treatment of BNL cells
      with HGF led to decreased expression of E-cadherin and increased expression of
      fibronectin, vimentin, snail, slug, COX-2, Akt, pAkt and increased migration,
      invasiveness and clonogenicity. We conclude that development of HCC is associated
      with upregulation of HGF which promotes EMT and carcinogenesis via upregulation
      of COX-2 and Akt. Consequently, HGF signaling may be targeted for therapy in
      advanced and metastatic HCC.

PMID- 21744258
TI  - Parallel synthesis of novel antitumor agents: 1,2,3-triazoles bearing
      biologically active sulfonamide moiety and their 3D-QSAR.
AB  - A 60-member 1,2,3-triazoles bearing biologically active sulfonamide moiety
      library was synthesized via azide-alkyne cycloaddition and examined for cytotoxic
      activity against human leukemia cell line HL-60. 25 of them were evaluated
      further in four additional cancer cell lines (HepG2, A549, PC3, SGC7901). Most of
      the 25 compounds showed moderate cytotoxic activities against the tested cell
      lines. Furthermore, the structure-activity relationships were discussed and a
      reliable 3D-QSAR model with good prediction (r2cv = 0.64, r2 = 0.958) was
      generated on the basis of our synthesized 1,2,3-triazoles for their cytotoxic
      activities against the HL-60 cell line. The contour map of the CoMFA should aid
      in the design of new antitumor agents.

PMID- 21744259
TI  - Recombinational histories of avian infectious bronchitis virus and turkey
      coronavirus.
AB  - Phylogenetic analysis of complete genomes of the avian coronaviruses avian
      infectious bronchitis (AIBV) and turkey coronavirus (TCoV) supported the
      hypothesis that numerous recombination events have occurred between these
      viruses. Although the two groups of viruses differed markedly in the sequence of
      the spike protein, the gene (S) encoding this protein showed no evidence of
      positive selection or of an elevated mutation rate. Rather, the data suggested
      that recombination events have homogenized the portions of the genome other than
      the S gene between the two groups of viruses, while continuing to maintain the
      two distinct, anciently diverged versions of the S gene. The latter hypothesis
      was supported by a phylogeny of S proteins from representative coronaviruses, in
      which S proteins of AIBV and TCoV fell in the same clade.

PMID- 21744260
TI  - Iron overdose: a contributor to adverse outcomes in randomized trials of anemia
      correction in CKD.
AB  - Administration of intravenous iron to supplement erythropoiesis stimulating
      agents (ESAs) has become a common practice in the management of anemia in
      patients with end-stage renal disease. Randomized clinical trials of anemia
      correction in this population have shown more adverse outcomes in CKD and ESRD
      patients assigned to the higher hemoglobin targets. Retrospective analysis of
      these trials suggests that morbidity is higher in subjects who fail to achieve
      the designated hemoglobin target and are typically exposed to higher doses of
      ESAs and iron than those that easily achieve the intended targets. Intravenous
      iron administration circumvents the natural biologic mechanisms for handling and
      utilization of iron. There is in vitro and in vivo evidence that intravenous iron
      preparations can cause oxidative stress, endothelial dysfunction, inflammation,
      impaired immunity, and renal injury. Since iron overload is known to promote
      endothelial dysfunction, cardiovascular disease, and immune dysfunction which are
      the leading causes of premature mortality in CKD and ESRD patients, it is
      imperative to exercise caution with the use of IV iron preparations in this
      population. The present review is intended to provide a brief overview of the
      potential adverse effects of the overzealous use of these agents.

PMID- 21744261
TI  - Characterization of novel small RNAs from tea (Camellia sinensis L.).
AB  - Small RNAs play important roles in plant development, metabolism, signal
      transduction and responses to biotic and abiotic stresses by affecting gene
      expression. Tea (Camellia sinensis L.) is an important commercial crop in the
      world. To understand the regulatory mechanisms involving small RNAs in tea
      metabolism, we constructed a small RNA (sRNA) library from its tea drink
      manufacturing tissue part i.e. topmost two leaves and a bud. For the first time,
      we isolated and cloned six novel small RNAs candidates from tea. These were
      predicted to target 67 genes responsible for various important plant functions.
      Isolated small RNAs were validated through expression analysis in young leaf and
      old leaf during non-dormant and dormant growth phases of tea. Results suggest the
      probable role of isolated small RNAs in development and seasonal variations of
      tea.

PMID- 21744262
TI  - Comparative analysis on the expression of inducible HSPs in the silkworm, Bombyx
      mori.
AB  - Heat shock proteins (HSPs), well-known in respond to various kinds of stress
      situations, have been widely studied in Drosophila. However, a few reports
      related to silkworm bombyx mori. Genetic and non-genetic factors affecting on the
      expression of some HSPs in heat-treated silkworm were studied at the present
      paper. The mRNA levels of HSPs were quantified by real-time quantitative RT-PCR
      method and compared with their expression in the proteome profiles. The results
      showed up-regulation of two small heat shock proteins (sHSPs), HSP19.9 and
      HSP20.4 and down-regulation of HSP70 in the fat body, testis and ovary of heat
      exposed larvae. Higher variation of the sHSPs than HSP70 was observed in the
      different conditions such as heat exposures and genetic backgrounds. Significant
      difference in the HSP19.9 expression between two breeds was observed which
      implied the importance of this gene in the genetic differences. There was
      significant difference between responses of severe and mild heat shocks after 4 h
      heat recovery. The HSPs expression in male was significantly higher than that in
      female silkworm larva for all transcript measurements (P < 0.001). Comparison of
      two methods of quantification showed a fair similarity between HSPs expression in
      the transcriptome and proteome levels. Nistari breed as a naturally thermo
      tolerant breed was expressed lower HSPs than a thermo-sensitive breed.

PMID- 21744263
TI  - Development of single-locus DNA microsatellite markers using 5'anchored ISSR-PCR
      method for the mangrove horseshoe crab, Carcinoscorpius rotundicauda (Latreille,
      1802) in Peninsular Malaysia.
AB  - Horseshoe crabs are said to be declining worldwide. However, there is still no
      published report on the status of horseshoe crabs in Malaysia. Thus, we report
      here eight informative microsatellite markers that were developed using the 5'
      anchored ISSR-PCR enrichment procedure to diagnose the population genetic
      structure of the mangrove horseshoe crab, Carcinoscorpius rotundicauda from
      Peninsular Malaysia. This set of markers was tested on 127 samples and showed
      polymorphism in this species. Hence they should be useful in future essential
      population genetic studies of these living fossils in the Southeast Asian region.

PMID- 21744264
TI  - Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with
      coronary artery disease in a population of Iranian patients with type 2 diabetes.
AB  - The relation of Two single nucleotide polymorphisms (SNPs) at the adiponectin
      locus (+45T/G and +276G/T) with coronary artery disease (CAD) is controversial.
      The aim of the present study was to evaluate the genetic influence of the
      adiponectin gene polymorphisms in the development of CAD among patients with Type
      2 diabetes (T2D). The adiponectin genotypes were detected by polymerase chain
      reaction and restriction analysis (PCR-RFLP) in our patients. Two adiponectin
      gene (ADIPOQ) SNPs (i.e. SNPs +45T>G and +276G>T) were genotyped in 114 Type 2
      diabetic subjects with CAD, and 127 Type 2 diabetic patients without CAD.
      Demographic and anthropometric data along with plasma biochemistry including
      lipids, glycemic indices, and adiponectin were collected. There was a significant
      difference in the distribution of genotypes of +45T/G and +276G/T between CAD and
      non-CAD individuals (P < 0.05). Based on our results SNP+276G>T is associated
      with decreased risk of CAD after adjustment for potential confounding factors
      [adjusted OR = 0.39 (95%CI: 0.22-0.68); P = 0.001]. Similar findings were not
      observed for the +45T>G SNP. Two haplotypes 45T-276T and 45G-276T were associated
      with a decreased risk of CAD [adjusted OR = 0.47 (95% CI: 0.32-0.94); P = 0.03
      and adjusted OR = 0.33 (95% CI: 0.13-0.83); P = 0.02 respectively]. No
      significant difference was observed between HOMA-IR, BMI, waist circumference,
      history of hypertension, HbA1C, and lipid concentrations regarding the two SNPs.
      In conclusion, these findings suggest that T allele of +276G>T SNP is
      significantly associated with decreased risk of CAD in T2D Patients. Also
      Haplotype analysis showed that two haplotypes 45T-276T and 45G-276T were
      associated with a decreased risk of CAD.

PMID- 21744265
TI  - Polymorphism in chemokine receptor genes and risk of acute myocardial infarction
      in North Indian population.
AB  - Chemokines regulates the trafficking of leukocytes to the site of inflammation
      hence may be implicated in cardiac events. Currently no consistent effects have
      been revealed their role in acute myocardial infarction (MI). The aim of current
      study was to investigate the impact of human chemokine receptor genetic variants,
      CCR5-Delta32 insertion/deletion, CCR5-59029-A/G, CX3CR1-V249I and CX3CR1-T280 M
      on acute MI. 230 acute MI and 300 controls were examined. Patients carrying CCR5
      Delta32 genotype were at three times higher risk of developing MI odds ratio (OR,
      3.24, CI 1.127-9.356, P = 0.04). Significant association was found with risk of
      acute MI in recipients who possessed homozygous 59029-A allele (OR 1.47, CI 1.03
      2.09, P = 0.03). While CX3CR1-I249 and M280 were found to be protective in MI
      patients with OR 0.46, CI 0.32-0.66, P < 0.0001 and OR 0.36, CI 0.24-0.55, P <
      0.0001, respectively. It might be possible that risk of acute MI is associated
      with genetic variation in chemokine receptors, i.e., CCR5 and CX3CR1.

PMID- 21744267
TI  - Genome-wide gene expression study indicates the anti-inflammatory effect of
      polarized light in recurrent childhood respiratory disease.
AB  - OBJECTIVES: The clinical and molecular effects of whole-body polarized light
      treatment on children suffering from recurrent respiratory infection were
      studied. METHODS: The incidence and duration of respiratory symptoms as well as
      the length of appropriate antibiotic therapy were measured. Simultaneously, the
      genome-wide gene expression pattern was examined by whole genome cDNA microarray
      in peripheral lymphocytes of children. RESULTS: Twenty of 25 children showed a
      marked clinical improvement, while in five of 25 had poor response or no changes.
      The gene expression pattern of the patients' peripheral lymphocytes was compared
      in favorable and poor responders. The lymphocytes of the children with a
      documented improved clinical response to polarized light therapy showed a
      decrease in the expression of chemokine genes, such as CXCL1, CXCL2, CXCL3, and
      IL-8, and in that of the TNFalpha gene. On the contrary, a rapid elevation was
      found in the expression of the gene encoding for CYP4F2, a leukotriene B4
      metabolizing enzyme. In children with poor clinical response to polarized light
      therapy, no similar changes were detected in the gene expression pattern of the
      lymphocytes. CONCLUSIONS: The improved clinical symptoms and modified gene
      expression profile of lymphocytes reveals an anti-inflammatory effect of whole
      body polarized light irradiation.

PMID- 21744266
TI  - Influence of chronic inflammation and autoimmunity on coronary calcifications and
      myocardial perfusion defects in systemic lupus erythematosus patients.
AB  - OBJECTIVE: Conventional risk factors for coronary artery disease fail to explain
      the increased frequency or cardiovascular morbidity in systemic lupus
      erythematosus (SLE) patients. This study was conducted to determine the possible
      influence of autoimmune and inflammatory phenomena markers on coronary artery
      calcifications and myocardial perfusion abnormalities in SLE patients. MATERIALS
      AND METHODS: Multi-detector computed tomography (MDCT)-based coronary calcium
      scoring and single photon emission computerized tomography (SPECT) studies (Tc
      99m sestamibi) were performed in 60 SLE patients in stable clinical condition,
      without a prior history of coronary artery disease. Laboratory evaluation
      included serum C-reactive protein (CRP), complement C3c and C4 components and
      antiphospholipid antibodies (aPL). The latter included anticardiolipin (aCL) and
      anti-beta2-glycoprotein I (abeta2GPI) antibodies, of both IgG and IgM classes,
      and lupus anticoagulant (LA) in plasma. RESULTS: SPECT revealed persistent
      perfusion defects in 22 (36.7%) patients and exercise-induced defects in eight
      (13.3%), while MDCT revealed coronary calcifications in 15 (25%). Calcium scores
      ranged from 1 to 843.2 (mean 113.5 +/- 259.7). No association was found between
      conventional coronary artery disease risk factors (obesity, hypertension, tobacco
      use, hyperlipidaemia, diabetes) nor CRP, C3c or C4 levels and coronary
      calcifications or myocardial perfusion defects. On the contrary, in patients with
      these pathologies, augmented autoimmunization was found, reflected by increased
      aCL IgG and antibeta2GPI IgG levels. In patients with aCL IgG >20 RU/ml or
      antibeta2GPI IgG >3 RU/ml, the relative risk of coronary calcification formation
      was 4.1 compared to patients with normal values. Accordingly, in LA-positive
      patients the relative risk of coronary calcification formation was 4.4 compared
      to LA-negative patients. CONCLUSIONS: Conventional risk factors for coronary
      artery disease as well as markers of an ongoing inflammation did not show any
      association with perfusion defects and/or coronary artery calcifications in SLE
      patients. On the contrary, calcified atherosclerotic plaques and myocardial
      perfusion defects were observed mainly in patients with elevated levels of
      anticardiolipin and abeta2GPI antibodies of the IgG class. It might be speculated
      that coronary artery calcifications and perfusion defects are a result of
      antiphospholipid antibodies-induced coronary artery microthrombosis.

PMID- 21744268
TI  - Synthetic peptide fragment (65-76) of monocyte chemotactic protein-1 (MCP-1)
      inhibits MCP-1 binding to heparin and possesses anti-inflammatory activity in
      stable angina patients after coronary stenting.
AB  - OBJECTIVE AND DESIGN: The peptide from C-terminal domain of MCP-1 (Ingramon) has
      been shown to inhibit monocyte migration and possess anti-inflammatory activity
      in animal models of inflammation and post-angioplasty restenosis. Here, we
      investigate the effect of Ingramon treatment on blood levels of acute-phase
      reactants and chemokines in patients after coronary stenting and the mechanisms
      of Ingramon anti-inflammatory activity. SUBJECTS: Eighty-seven patients with
      ischemic heart disease (IHD) who faced the necessity of coronary angiography (CA)
      were enrolled. In 67 patients, one-stage coronary stenting was performed; 33 of
      them were treated with Ingramon in addition to standard therapy. Twenty patients
      underwent CA only. METHODS: High-sensitivity C-reactive protein (hsCRP) and
      fibrinogen blood levels were detected routinely. The chemokine concentration in
      plasma was measured by enzyme-linked immunosorbent assay (ELISA) or cytometric
      bead array-based immunoassay. Intracellular Ca(2+) levels and cell surface
      integrin exposure were assayed by flow cytometry. MCP-1 dimerization was studied
      by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). MCP-1
      heparin binding was assessed with a biosensor and ELISA. RESULTS AND CONCLUSIONS:
      Ingramon treatment was accompanied by less pronounced elevation of hsCRP and
      fibrinogen levels and decreased MCP-1 concentration in plasma in patients after
      coronary stenting. Ingramon had no effect on MCP-1 interaction with cell
      receptors or MCP-1 dimerization, but inhibited MCP-1 binding to heparin. The anti
      inflammatory activity of the peptide may be mediated by an impaired chemokine
      interaction with glycosaminoglycans.

PMID- 21744269
TI  - Experimental investigation of collagen waviness and orientation in the arterial
      adventitia using confocal laser scanning microscopy.
AB  - Mechanical properties of the adventitia are largely determined by the
      organization of collagen fibers. Measurements on the waviness and orientation of
      collagen, particularly at the zero-stress state, are necessary to relate the
      structural organization of collagen to the mechanical response of the adventitia.
      Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning
      microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid
      arteries ex vivo. The arteries were cut open along their longitudinal axes to get
      the zero-stress state. We used semi-manual and automatic techniques to measure
      parameters related to the waviness and orientation of fibers. Our results showed
      that the straightness parameter (defined as the ratio between the distances of
      endpoints of a fiber to its length) was distributed with a beta distribution
      (mean value 0.72, variance 0.028) and did not depend on the mean angle
      orientation of fibers. Local angular density distributions revealed four axially
      symmetric families of fibers with mean directions of 0 degrees , 90 degrees , 43
      degrees  and -43 degrees , with respect to the axial direction of the artery, and
      corresponding circular standard deviations of 40 degrees , 47 degrees , 37
      degrees  and 37 degrees . The distribution of local orientations was shifted to
      the circumferential direction when measured in arteries at the zero-load state
      (intact), as compared to arteries at the zero-stress state (cut-open).
      Information on collagen fiber waviness and orientation, such as obtained in this
      study, could be used to develop structural models of the adventitia, providing
      better means for analyzing and understanding the mechanical properties of
      vascular wall.

PMID- 21744270
TI  - "Crossed renal ectopia".

PMID- 21744272
TI  - Polysaccharides purified from the submerged culture of Ganoderma formosanum
      stimulate macrophage activation and protect mice against Listeria monocytogenes
      infection.
AB  - The bioactive components of Ganoderma formosanum have not yet been characterized.
      We investigated the immunomodulatory activities of the extracellular
      polysaccharides produced from a submerged mycelial culture of G. formosanum. The
      polysaccharides were mainly composed of D-mannose, D-galactose and D-glucose.
      After gel filtration chromatography, three polysaccharide fractions (PS-F1, PS-F2
      and PS-F3) were purified. PS-F2 stimulated mouse RAW264.7 macrophages to produce
      TNF-alpha and nitric oxide, and enhanced the phagocytic activity of macrophages.
      PS-F2 challenge in mice triggered an acute inflammatory response characterized by
      the recruitment of neutrophils and monocytes, which protected mice from
      subsequent infection of Listeria monocytogenes. The results indicate that the
      heteropolysaccharides produced by G. formosanum can activate the innate immune
      response on macrophages.

PMID- 21744273
TI  - Efflux of bile acids in Lactobacillus reuteri is mediated by ATP.
AB  - PURPOSE OF WORK: To study whether an active bile acid (BA) efflux occurs in
      Lactobacillus reuteri CRL 1098 as well as the nature (ATP or proton motive force
      [PMF] mediated primary transport) of the BA extrusion mechanism. BAs are powerful
      detergents which disorganize the lipid bilayer structure of cellular membranes.
      Specific bile resistance mechanisms (bile efflux, bile salt hydrolysis, and
      intrinsic architecture and composition of cell membrane the most prevalent) have
      been described in intestinal bacteria. L. reuteri, showed a significant degree of
      resistance to the toxic action of BA and the presence of an active efflux ATP
      dependent of conjugated (taurocholic [TCA]) and free (cholic [CA]) BA in the CRL
      1098 strain is now reported. However, due the high pKa (5.5) of cholic acid (CA)
      compared with the conjugated species, a significant fraction (between 35 and 50%
      at pH 6.5 and 5.2, respectively) of free BA also diffused passively, even in the
      absence of ATP. To our knowledge, our results represent the first evidence of ATP
      as the energy source involved in the BA extrusion in L. reuteri.

PMID- 21744274
TI  - Enantioselective esterification of (R,S)-2-methylalkanoic acid with Carica papaya
      lipase in organic solvents.
AB  - Isooctane was the best reaction medium for the enantioselective esterification of
      (R,S)-2-methylalkanoic acid with n-butanol using Carica papaya lipase as
      catalyst. Increasing linear alkyl-chain length of racemic 2-methylalkanoic acids
      from ethyl to hexyl increased the enantioselectivity (E) from 2.1 to 98.2 for the
      esterification of racemic 2-methylalkanoic acids with n-butanol at 35 degrees C.
      Decreasing reaction temperature from 40 to 20 degrees C increased the
      enantioselectivity (E) from 14 to 33 for the esterification of racemic 2
      methylhexanoic acids with n-butanol. We obtained a maximum enantioselectivity, of
      E = 24.3, for the enantioselective esterification of racemic 2-methylhexanoic
      acids with n-butanol in isooctane at water activity 0.33, and at 35 degrees C.

PMID- 21744275
TI  - Bio-oxidation of H2S by Sulfolobus metallicus.
AB  - Sulfolobus metallicus is a hyperthermophilic and chemolithoautotrophic archaeon
      that uses elemental sulfur as an energy source. Its ability to oxidize H(2)S was
      measured either in the presence or absence of elemental sulphur, showing its
      ability for using both as an energy source. A biotrickling filter was set up and
      a biofilm of S. metallicus was established over the support. The maximum removal
      capacity of the biotrickling filter reached at 55 degrees C was 40 g S/m(3)h for
      input loads higher than 70 g S/m(3)h. Thus, S. metallicus can be used in a
      biofiltration system for the treatment of waste gas emissions at high
      temperatures contaminated with H(2)S.

PMID- 21744276
TI  - Efficient and specific conversion of 9-lipoxygenase hydroperoxides in the
      beetroot. Formation of pinellic acid.
AB  - The linoleate 9-lipoxygenase product 9(S)-hydroperoxy-10(E),12(Z)-octadecadienoic
      acid was stirred with a crude enzyme preparation from the beetroot (Beta vulgaris
      ssp. vulgaris var. vulgaris) to afford a product consisting of 95% of
      9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acid (pinellic acid). The
      linolenic acid-derived hydroperoxide 9(S)-hydroperoxy-10(E),12(Z),15(Z)
      octadecatrienoic acid was converted in an analogous way into 9(S),12(S),13(S)
      trihydroxy-10(E),15(Z)-octadecadienoic acid (fulgidic acid). On the other hand,
      the 13-lipoxygenase-generated hydroperoxides of linoleic or linolenic acids
      failed to produce significant amounts of trihydroxy acids. Short-time incubation
      of 9(S)-hydroperoxy-10(E),12(Z)-octadecadienoic acid afforded the epoxy alcohol
      12(R),13(S)-epoxy-9(S)-hydroxy-10(E)-octadecenoic acid as the main product
      indicating the sequence 9-hydroperoxide -> epoxy alcohol -> trihydroxy acid
      catalyzed by epoxy alcohol synthase and epoxide hydrolase activities,
      respectively. The high capacity of the enzyme system detected in beetroot
      combined with a simple isolation protocol made possible by the low amounts of
      endogenous lipids in the enzyme preparation offered an easy access to pinellic
      and fulgidic acids for use in biological and medical studies.

PMID- 21744277
TI  - 2-Polyunsaturated acyl lysophosphatidylethanolamine attenuates inflammatory
      response in zymosan A-induced peritonitis in mice.
AB  - In the present study, the anti-inflammatory action of
      lysophosphatidylethanolamine (lysoPtdEtn), orally administered, in zymosan A
      induced peritonitis was examined. Oral administration of 2-DHA-lysoPtdEtn
      (ED(50), ~111 MUg/kg) or 2-ARA-lysoPtdEtn (ED(50), 221 MUg/kg) was found to
      inhibit the plasma leakage in mice treated with zymosan A. In support of this, 2
      polyunsaturated acyl-lysoPtdEtn diminished the formation of LTC(4), a lipid
      mediator responsible for vascular permeability. Next, 2-DHA-lysoPtdEtn (ED(50),
      110 MUg/kg) or 2-ARA-lysoPtdEtn (ED(50), 123 MUg/kg) effectively inhibited the
      leukocyte extravasation into the peritoneum. Consistent with this, each
      polyunsaturated-lysoPtdEtn diminished the formation of LTB(4) and 12-HETE, potent
      chemotactic factors. Additionally, the level of pro-inflammatory mediator (IL-1
      beta, IL-6, TNF-alpha or NO) was lowered remarkably in contrast to the
      augmentation of anti-inflammatory interleukin IL-10. Furthermore, 2-(15-HETE)
      lysoPtdEtn and 2-(17-HDHE)-lysoPtdEtn, 15-lipoxygenation product of 2-ARA
      lysoPtdEtn and 2-DHA-lysoPtdEtn, respectively, were more potent than
      corresponding lysoPtdEtn, suggesting the action of 2-acyl-lysoPtdEtn might be
      expressed through 15-lipoxygenation. In support of this, the formation of 15-HETE
      and LXA(4) was upgraded in accordance with an increasing dose of 2-ARA
      lysoPtdEtn. Separately, anti-inflammatory actions, 2-polyunsaturated acyl
      lysoPtdEtns also drastically diminished leukocyte infiltration in a later phase
      of zymosan A-induced peritonitis, indicating that these lipids also possess pro
      resolving activity. Taken together, it is suggested that polyunsaturated
      lysoPtdEtns and their lipoxygenation derivatives, could be classified as potent
      anti-inflammatory lipids.

PMID- 21744278
TI  - JNK inhibition by SP600125 attenuates trans-10, cis-12 conjugated linoleic acid
      mediated regulation of inflammatory and lipogenic gene expression.
AB  - Supplementation with a mixture of trans-10, cis-12 (t10,c12) and cis-9, trans-11
      (c9,t11) isomers of conjugated linoleic acid (CLA), or t10,c12 CLA alone, reduces
      body weight and fat deposition in animals and some humans. However, these anti
      obesity actions of t10,c12 CLA are routinely accompanied by increased markers of
      inflammation and insulin resistance. Thus, we examined the extent to which
      blocking c-Jun NH2-terminal kinase (JNK) signaling using the JNK inhibitor
      SP600125 attenuated markers of inflammation and insulin resistance in primary
      human adipocytes treated with t10,c12 CLA. SP600125 attenuated t10,c12 CLA
      mediated phosphorylation of cJun and increased protein levels of activating
      transcription factor (ATF) 3, two downstream targets of JNK. SP600125 attenuated
      t10,c12 CLA-mediated induction of inflammatory genes, including interleukin (IL)
      6, IL-8, IL-1beta, ATF3, monocyte chemoattractant protein (MCP)-1, and
      cyclooxygenase-2. Consistent with these data, SP600125 prevented t10,c12 CLA
      mediated secretion of IL-8, IL-6, and MCP-1. SP600125 prevented t10,c12 CLA
      suppression of lipogenic genes including peroxisome proliferator activated
      receptor gamma, liver X receptor, sterol regulatory element binding protein,
      acetyl-CoA carboxylase, and stearoyl-CoA desaturase. Additionally, SP600125
      blocked t10,c12 CLA-mediated induction of suppressor of cytokine synthesis-3 and
      suppression of adiponectin and insulin-dependent glucose transporter 4 mRNA
      levels. Collectively, these data suggest that JNK signaling plays an important
      role in t10,c12 CLA-mediated regulation of inflammatory and lipogenic gene
      expression in primary cultures of human adipocytes.

PMID- 21744279
TI  - Coronary arterioles in type 2 diabetic (db/db) mice undergo a distinct pattern of
      remodeling associated with decreased vessel stiffness.
AB  - Little is known about the impact of type 2 diabetes mellitus (DM) on coronary
      arteriole remodeling. The aim of this study was to determine the mechanisms that
      underlie coronary arteriole structural remodeling in type 2 diabetic (db/db)
      mice. Passive structural properties of septal coronary arterioles isolated from
      12- to 16-week-old diabetic db/db and control mice were assessed by pressure
      myography. Coronary arterioles from 12-week-old db/db mice were structurally
      similar to age-matched controls. By 16 weeks of age, coronary wall thickness was
      increased in db/db arterioles (p < 0.01), while luminal diameter was reduced
      (control: 118 +/- 5 MUm; db/db: 102 +/- 4 MUm, p < 0.05), augmenting the wall-to
      lumen ratio by 58% (control: 5.9 +/- 0.6; db/db: 9.5 +/- 0.4, p < 0.001). Inward
      hypertrophic remodeling was accompanied by a 56% decrease in incremental elastic
      modulus (p < 0.05, indicating decreased vessel coronary wall stiffness) and a
      ~30% reduction in coronary flow reserve (CFR) in diabetic mice. Interestingly,
      aortic pulse wave velocity and femoral artery incremental elastic modulus were
      increased (p < 0.05) in db/db mice, indicating macrovascular stiffness. Molecular
      tissue analysis revealed increased elastin-to-collagen ratio in diabetic
      coronaries when compared to control and a decrease in the same ratio in the
      diabetic aortas. These data show that coronary arterioles isolated from type 2
      diabetic mice undergo inward hypertrophic remodeling associated with decreased
      stiffness and increased elastin-to-collagen ratio which results in a decreased
      CFR. This study suggests that coronary microvessels undergo a different pattern
      of remodeling from macrovessels in type 2 DM.

PMID- 21744280
TI  - Transmission of multiple resistant Salmonella Concord from internationally
      adopted children to their adoptive families and social environment: proposition
      of guidelines.
AB  - Since 2004, an increasing number of multidrug-resistant Salmonella serovar
      Concord infections have been isolated in Belgium among children adopted from
      Ethiopia. The patients or their family were interviewed and the isolates were
      subtyped. Between 2004 and 2009, a total of 39 Salmonella Concord infections were
      isolated from patients. Thirty-four isolates presented a multidrug resistance
      including resistance to extended-spectrum cephalosporins. Thirty-six cases
      involved children and 30 of these were adopted from Ethiopia. One case was due to
      contact with an adopted child and for the other 5 cases no direct epidemiological
      link with Ethiopia could be found, although four isolates displayed the same
      patterns observed on the adoptees' isolates, strongly suggesting a phylogenetic
      relationship with the Ethiopian isolates. Our study confirmed the emergence in
      Europe of S. Concord isolates resistant to third-generation cephalosporin among
      Ethiopian adoptees. We have demonstrated that transmission (intra- and extra
      familial) can happen even if the frequency seems to be low. The presence and the
      transmission of such a multidrug-resistant Salmonella infection constitute a
      major concern, since such strains could jeopardize classical antibiotic therapy
      in patients at risk. This study provides useful information for parents adopting
      children and for their family practitioner.

PMID- 21744281
TI  - Clinical features of Clostridium difficile infection and molecular
      characterization of the isolated strains in a cohort of Danish hospitalized
      patients.
AB  - The purpose of this study was to compare clinical features of Clostridium
      difficile infection (CDI) to toxin gene profiles of the strains isolated from
      Danish hospitalized patients. C. difficile isolates were characterized by PCR
      based molecular typing methods including toxin gene profiling and analysis of
      deletions and truncating mutations in the toxin regulating gene tcdC. Clinical
      features were obtained by questionnaire. Thirty percent of the CDI cases were
      classified as community-acquired. Infection by C. difficile with genes encoding
      both toxin A, toxin B and the binary toxin was significantly associated with
      hospital-acquired/healthcare-associated CDI compared to community-acquired CDI.
      Significantly higher leukocyte counts and more severe clinical manifestations
      were observed in patients infected by C. difficile containing genes also encoding
      the binary toxin together with toxin A and B compared to patients infected by C.
      difficile harbouring only toxin A and B. In conclusion, infection by C. difficile
      harbouring genes encoding both toxin A, toxin B and the binary toxin were
      associated with hospital acquisition, higher leukocyte counts and severe clinical
      disease.

PMID- 21744282
TI  - The scarpa lift--a novel technique for minimal invasive medial thigh lifts.
AB  - Abdominoplasty and lower body lift procedures are the most common and sufficient
      procedures to correct abdominal tissue redundancy. Frequently, patients who
      undergo these procedures have lost a relevant amount of weight and additionally
      present tissue redundancy in the area of the medial thighs. Patients with mild to
      moderate skin surplus in the medial thigh region often refuse an additional scar
      in this specific region. For these cases, the medial thigh region can be
      indirectly treated by the vertical scarpa lift, sparing the medial thigh approach
      and consequent complications such as scar descent or vulvar distortion.
      Additionally, the lymphatic vessels below the scarpa fascia can be preserved,
      reducing the postoperative abdominal seroma rate.

PMID- 21744283
TI  - Safety and efficacy of Roux-en-Y gastric bypass to treat type 2 diabetes mellitus
      in non-severely obese patients.
AB  - The efficacy of Roux-en-Y gastric bypass (RYGB) to control type 2 diabetes
      mellitus (T2DM) has been demonstrated in morbidly obese patients. Surgical
      procedures primarily focused on T2DM control in patients with body mass index
      (BMI) < 35 kg/m(2) have shown to effectively induce remission of T2DM. However,
      only few reports have evaluated the safety and efficacy of RYGB in this group of
      patients. The aim of this study is to assess the safety and efficacy of RYGB in
      TD2M patients with BMI < 35 kg/m(2). All T2DM patients with BMI < 35 kg/m(2) and
      at least 12 months of follow-up who underwent laparoscopic RYGB were included.
      Safety of the procedure was evaluated according to mortality, need of
      reoperation/conversion, and complication rates. Metabolic parameters were
      evaluated at baseline and 6, 12, and 24 months after surgery. Thirty patients
      were included. Seventeen (56.6%) were women. Age, BMI, and duration of diabetes
      were 48 +/- 9 years, 33.7 +/- 1.2 kg/m(2), 4 +/- 2.9 years, respectively. No
      mortality was observed. No conversion/reoperation was needed. Average length of
      stay was 3.2 +/- 0.9 days. Early and late postoperative complications were
      observed in five (16.6%) and five (16.6%) patients, respectively. Twelve months
      after surgery, remission was observed in 25 of 30 patients (83.3%). After 2
      years, remission was achieved in 13 of 20 patients (65%), and hemoglobin A1c
      decreased from 8.1 +/- 1.8% to 5.9 +/- 1.1% and homeostasis model assessment of
      insulin resistance from 5.7 +/- 3.2 to 1.9 +/- 0.8 after 12 months. RYGB is a
      safe and effective procedure to induce T2DM remission in otherwise not eligible
      patients for bariatric surgery. Evidence from prospective studies is needed to
      validate this approach.

PMID- 21744284
TI  - Platelet-rich plasma in mono-segmental posterior lumbar interbody fusion.
AB  - INTRODUCTION: The results of platelet-rich plasma (PRP) in spinal fusion
      applications are limited and controversial. Both beneficial and inhibitory
      effects have been shown. In this prospective randomised controlled trial, our
      objective was to assess both the clinical and radiological effect of PRP when
      added to autograft iliac crest bone in posterior lumbar interbody fusion. METHODS
      AND MATERIALS: Forty patients were recruited for the study fulfilling strict
      entry requirements and were randomised with a 1:1 ratio. In each group, one
      patient was lost to follow-up. Thirtyeight patients completed the Visual Analogue
      Scale (VAS), the Oswestry Disability Index (ODI), and the Short-Form 36 (SF-36)
      preoperatively and postoperatively at 3, 6, 12, and 24 months, respectively. CT
      scans of the lumbar spine were taken at 3, 6, and 12 months. Posterior
      stabilisation was achieved with pedicle screws and interbody fusion was aimed at
      with carbon cages filled with autologous bone. RESULTS: Baseline demographic data
      (age, sex, smoking history, preoperative outcome measures) showed no relevant
      difference between groups. For patients who received autograft only, the mean VAS
      improved by 4.0 points (p < 0.01), mean ODI improved by 32.1 points (p < 0.001),
      and mean SF-36 showed statistically significant improvement in each of the eight
      domains and in the physical (p < 0.001) and mental (p < 0.001) component summary
      measures. For patients who received autograft with PRP, the mean VAS improved by
      4.92 points (p < 0.01), mean ODI improved by 30 points (p < 0.001), and mean SF
      36 showed statistically significant improvement in six of the eight domains (p <
      0.02) and in the physical (p = 0.016) and mental (p < 0.001) component summary
      measures. The improvement of the VAS score and the physical component summary
      score was more pronounced in patients who received autograft with PRP. These
      differences were, however, not statistically significant. CT-scans showed
      uneventful osseous healing in all but one patient with no difference between
      groups. CONCLUSION: In this prospective randomised controlled clinical and
      radiological trial, adding PRP in posterior lumbar interbody fusion did not lead
      to a substantial improvement or deterioration when compared with autologous bone
      only. No inhibitory effect of PRP was observed on CT-scans. From a clinical and
      radiological point of view, the use of PRP seems to be justified in posterior
      lumbar interbody fusion surgery. From an economical point of view, the expense of
      using PRP cannot be justified until statistical significance can be reached in a
      larger study.

PMID- 21744285
TI  - Diversity in autoimmunity against retinal, neuronal, and axonal antigens in
      acquired neuro-retinopathy.
AB  - PURPOSE: Autoimmune retinopathies and optic neuropathies are complex disorders of
      the retina and the optic nerve, in which patients develop autoantibodies (AAbs)
      against retinal and optic nerve proteins. Autoimmunity might significantly
      influence the outcome of retinal and optic nerve degenerative process but the
      pathogenic process is not fully elucidated. To better understand the role of AAbs
      in pathogenicity of these suspected autoimmune visual disorders, we focused on
      unique AAbs specificities associated with the syndrome to identify their
      antigenic targets in the optic nerve and retina. METHODS: Serum samples were
      obtained from patients, whose visual disorders were potentially autoimmune in
      nature, including patients with cancer with possible paraneoplastic syndrome.
      Autoantibodies were tested against human optic nerve and retinal antigens for
      specificity by Western blotting and immunofluorescence. RESULTS: Out of 209
      tested for anti-optic nerve autoantibodies, 55% showed specific neuronal
      autoantibodies. The repertoire of anti-optic nerve autoantibodies often differed
      from anti-retinal antibodies. The major antigenic targets for these antibodies
      could be divided into four groups. Autoantibodies specific to classical
      glycolytic enzymes involved in energy production (alpha and gamma enolases,
      glyceraldehyde 3-phosphate dehydrogenase) also reacted with retinal antigens.
      Autoantibodies targeted neuronal-specific myelin proteins (MBP, MOG), aquaporin
      4, and collapsing response mediator protein 5 reacted with optic nerve antigens.
      They showed immunostaining of axons and myelin in the optic nerve as determined
      by double immunofluorescence. CONCLUSION: We identified novel neuronal
      autoantigens not previously known to be associated with acquired autoimmune
      retinopathy and optic neuropathy. Knowledge of the full autoantibody repertoire
      perpetuating this syndrome is an important first requirement in increasing our
      understanding of the autoimmune process to facilitate better diagnosis,
      prognosis, and treatment.

PMID- 21744286
TI  - Chitinase production in solid-state fermentation from Oerskovia xanthineolytica
      NCIM 2839 and its application in fungal protoplasts formation.
AB  - The present study reports the economic production of thermostable chitinase
      production from Oerskovia xanthineolytica NCIM 2839 by solid-state fermentation
      (SSF) technique and its application in fungal protoplasts formation. The
      Oerskovia xanthineolytica NCIM 2839 was found to produce thermostable chitinase
      148 U g(-1) of solid substrate in SSF using wheat bran with colloidal chitin as
      base. Protoplasts of A. niger were formed by using crude chitinase produced in
      SSF and formed protoplasts were confirmed by using scanning electron microscopy.
      This is the simple and economical method for protoplast formation which makes it
      possible applications in strain improvement of various fungi by protoplasts
      fusion in Biotechnological industries.

PMID- 21744287
TI  - Increase of the Bacillus thuringiensis secreted toxicity against lepidopteron
      larvae by homologous expression of the vip3LB gene during sporulation stage.
AB  - The Vegetative insecticidal Vip3A proteins display a wide range of insecticidal
      spectrum against several agricultural insect pests. The fact that the expression
      of vip3 genes occurs only during the vegetative growth phase of Bacillus
      thuringiensis is a limiting factor in term of production level. Therefore,
      extending the synthesis of the Vip proteins to the sporulation phase is a good
      alternative to reach high levels of toxin synthesis. In this study, we have
      demonstrated that the maximal production of the secreted Vip3LB (also called
      Vip3Aa16) during the growth of the wild-type strain B. thuringiensis BUPM 95 is
      reached at the end of the vegetative growth phase, and that the protein remains
      relatively stable in the culture supernatant during the late sporulation stages.
      The vip3LB gene was cloned and expressed under the control of the sporulation
      dependant promoters BtI and BtII in B. thuringiensis BUPM 106 (Vip3(-)) and BUPM
      95 (Vip3(+)) strains. The examination of the culture supernatants during the
      sporulation phase evidenced the synthesis of Vip3LB and its toxicity against the
      second-instars larvae of the Lepidopteron insect Spodoptera littoralis for the
      recombinant BUPM 106. Moreover, there was an increase of the Vip3LB synthesis
      level and an enhancement of the oral toxicity for the recombinant BUPM 95
      resulting from the expression of the vip3LB gene during both the vegetative and
      sporulation phases and the relative stability of the Vip3LB protein.

PMID- 21744288
TI  - Dasytricha dominance in Surti buffalo rumen revealed by 18S rRNA sequences and
      real-time PCR assay.
AB  - The genetic diversity of protozoa in Surti buffalo rumen was studied by amplified
      ribosomal DNA restriction analysis, 18S rDNA sequence homology and phylogenetic
      and Real-time PCR analysis methods. Three animals were fed diet comprised green
      fodder Napier bajra 21 (Pennisetum purpureum), mature pasture grass (Dicanthium
      annulatum) and concentrate mixture (20% crude protein, 65% total digestible
      nutrients). A protozoa-specific primer (P-SSU-342f) and a eukarya-specific primer
      (Medlin B) were used to amplify a 1,360 bp fragment of DNA encoding protozoal
      small subunit (SSU) ribosomal RNA from rumen fluid. A total of 91 clones were
      examined and identified 14 different 18S RNA sequences based on PCR-RFLP pattern.
      These 14 phylotypes were distributed into four genera-based 18S rDNA database
      sequences and identified as Dasytricha (57 clones), Isotricha (14 clones),
      Ostracodinium (11 clones) and Polyplastron (9 clones). Phylogenetic analyses were
      also used to infer the makeup of protozoa communities in the rumen of Surti
      buffalo. Out of 14 sequences, 8 sequences (69 clones) clustered with the
      Dasytricha ruminantium-like clone and 4 sequences (13 clones) were also
      phylogenetically placed with the Isotricha prostoma-like clone. Moreover, 2
      phylotypes (9 clones) were related to Polyplastron multivesiculatum-like clone.
      In addition, the number of 18S rDNA gene copies of Dasytricha ruminantium (0.05%
      to ciliate protozoa) was higher than Entodinium sp. (2.0 * 10(5) vs. 1.3 * 10(4))
      in per ml ruminal fluid.

PMID- 21744289
TI  - Organizing pneumonia: a kaleidoscope of concepts and morphologies.
AB  - The basic histopathological pattern of organizing pneumonia (OP) is well
      recognized, but the contexts in which it is encountered continue to increase. In
      parallel with an appreciation of new causes and associations of OP, an
      understanding of OP in the spectrum of lung injury and repair has evolved. There
      is an increasing array of HRCT manifestations of OP, some of which have only
      recently been described. This article concentrates on new concepts surrounding OP
      and highlights newly described imaging patterns.

PMID- 21744290
TI  - Push, pull, and reverse: self-interest, responsibility, and the global health
      care worker shortage.
AB  - The world is suffering from a dearth of health care workers, and sub-Saharan
      Africa, an area of great need, is experiencing the worst shortage. Developed
      countries are making the problem worse by luring health care workers away from
      the countries that need them most, while developing countries do not have the
      resources to stem the flow or even replace those lost. Postmodern philosopher
      Emmanuel Levinas offers a unique ethical framework that is helpful in assessing
      both the irresponsibility inherent in the current global health care situation
      and the responsibility and obligation held by the stakeholders involved in this
      global crisis. Drawing on Levinas' exploration of individual freedom and self
      pursuit, infinite responsibility for the Other, and the potential emergence of a
      just community, we demonstrate its effectiveness in explaining the health care
      worker crisis, and we argue in favor of a variety of policy and development
      assistance measures that are grounded in an orientation of non-indifference
      toward Others.

PMID- 21744291
TI  - Hypercholesterolaemia, signs of islet microangiopathy and altered angiogenesis
      precede onset of type 2 diabetes in the Goto-Kakizaki (GK) rat.
AB  - AIMS/HYPOTHESIS: The adult non-obese Goto-Kakizaki (GK) rat model of type 2
      diabetes, particularly females, carries in addition to hyperglycaemia a genetic
      predisposition towards dyslipidaemia, including hypercholesterolaemia. As
      cholesterol-induced atherosclerosis may be programmed in utero, we looked for
      signs of perinatal lipid alterations and islet microangiopathy. We hypothesise
      that such alterations contribute towards defective pancreas/islet vascularisation
      that might, in turn, lead to decreased beta cell mass. Accordingly, we also
      evaluated islet inflammation and endothelial activation in both prediabetic and
      diabetic animals. METHODS: Blood, liver and pancreas were collected from
      embryonic day (E)21 fetuses, 7-day-old prediabetic neonates and 2.5-month-old
      diabetic GK rats and Wistar controls for analysis/quantification of: (1) systemic
      variables, particularly lipids; (2) cholesterol-linked hepatic enzyme mRNA
      expression and/or activity; (3) pancreas (fetuses) or collagenase-isolated islet
      (neonates/adults) gene expression using Oligo GEArray microarrays targeted at rat
      endothelium, cardiovascular disease biomarkers and angiogenesis, and/or RT-PCR;
      and (4) pancreas endothelial immunochemistry: nestin (fetuses) or von Willebrand
      factor (neonates). RESULTS: Systemic and hepatic cholesterol anomalies already
      exist in GK fetuses and neonates. Hyperglycaemic GK fetuses exhibit a similar
      percentage decrease in total pancreas and islet vascularisation and beta cell
      mass. Normoglycaemic GK neonates show systemic inflammation, signs of islet pre
      microangiopathy, disturbed angiogenesis, collapsed vascularisation and altered
      pancreas development. Concomitantly, GK neonates exhibit elevated defence
      mechanisms. CONCLUSIONS/INTERPRETATION: These data suggest an autoinflammatory
      disease, triggered by in utero programming of cholesterol-induced islet
      microangiopathy interacting with chronic hyperglycaemia in GK rats. During the
      perinatal period, GK rats show also a marked deficient islet vascularisation in
      conjunction with decreased beta cell mass.

PMID- 21744292
TI  - Treatment of acute heart failure using levosimendan for a patient with dilated
      cardiomyopathy, chronic renal failure, and hypertension.
AB  - The clinical and hemodynamic effects of compassionate therapy with levosimendan
      were evaluated in a 14-year-old patient with end-stage renal disease and arterial
      hypertension secondary to glycogenosis type Ia. The patient previously had normal
      heart function but experienced acute development of severe myocardial dysfunction
      resistant to diuretic therapy and inotropic support. Levosimendan administration
      was followed by a marked clinical and echocardiographic improvement. The authors
      believe that levosimendan may be useful for cases of resistant acute heart
      failure with arterial hypertension. Although administration of levosimendan is
      not recommended for patients with chronic renal disease, no adverse effect was
      observed. Therapeutic action for these patients seems to last longer than for
      patients with a normal kidney.

PMID- 21744293
TI  - Heat acclimation-induced changes in heart glycogen/glucose metabolism in rats.
AB  - Based on the observation that heat acclimation is a slowly developing response,
      evoked by continuous exposure to moderate heat, we investigated the time
      dependent acclimatory changes of heart glycogen metabolism. Cardiac levels of key
      carbohydrate-related enzymes and substrates were studied in the function of the
      duration of short-term (STHA; 6, 12, 24 and 48 h) and long-term heat acclimation
      (LTHA; 7, 14, 21 and 30 days) to high environmental temperature (35 +/- 1 degrees
      C). The changes in heart glycogen metabolism during STHA could be separated in
      two phases: up to 12 h exposure, where significant decrease of the heart glycogen
      (Glk), glucose-6-phosphate (G6P), hexokinase (HK) activity as well as increase of
      heart glucose was observed; and from 24 to 48 h exposure, manifested with
      elevation of Glk, Glu, glycogen phosphorylase a (GPa), phosphofructokinase (PFK)
      and HK activities. The metabolic changes in the period of LTHA could also be seen
      as separate phases: in a period of 7-14 days of heat exposure there was an
      increase of heart Glk, Glu, G6P, HK, as well as a decrease of GPa and PFK, while
      in the period of 21-28 days there was more intensive rebound of Glk and G6P,
      increase of GPa activity and non-significant changes of Glu, HK and PFK. The
      results obtained have showed that acclimation to moderate hyperthermic
      environment has caused significant changes in examined parameters which differ
      depending on duration to the exposure: intensive stress-induced glycogenolytic
      and glycolytic processes in the period of STHA and intensive energy sparing,
      manifested by Glk deposition in the period of LTHA.

PMID- 21744294
TI  - Putative role of intracellular Zn(2+) release during oxidative stress: a trigger
      to restore cellular thiol content that is decreased by oxidative stress.
AB  - Although the ability of zinc to retard the oxidative process has been recognized
      for many years, zinc itself has been reported to induce oxidative stress. In
      order to give some insights into elucidating the role of intracellular Zn(2+) in
      cells suffering from oxidative stress, the effects of N-ethylmaleimide (NEM) and
      ZnCl(2) on cellular thiol content and intracellular Zn(2+) concentration were
      studied by use of 5-chloromethylfluorescein diacetate (5-CMF-DA) and FluoZin-3
      pentaacetoxymethyl ester (FluoZin-3-AM) in rat thymocytes. The treatment of cells
      with NEM attenuated 5-CMF fluorescence and augmented FluoZin-3 fluorescence in a
      dose-dependent manner. These NEM-induced phenomena were observed under external
      Zn(2+)-free conditions. Results suggest that NEM decreases cellular thiol content
      and induces intracellular Zn(2+) release. Micromolar ZnCl(2) dose-dependently
      augmented both FluoZin-3 and 5-CMF fluorescences, suggesting that the elevation
      of intracellular Zn(2+) concentration increases cellular thiol content. Taken
      together, it is hypothesized that intracellular Zn(2+) release during oxidative
      stress is a trigger to restore cellular thiol content that is decreased by
      oxidative stress.

PMID- 21744295
TI  - Associations of participation in service activities with academic, behavioral,
      and civic outcomes of adolescents at varying risk levels.
AB  - Youth who participate in service activities differ from those who do not on a
      number of key demographic characteristics like socio-economic status and other
      indicators of risk; and most studies demonstrating positive outcomes among
      service participants employ small non-representative samples. Thus, there is
      little evidence as to whether the outcomes associated with service participation
      are similar among students with varying levels of risk. The National Household
      Education Survey of 1999, a large nationally representative cross-sectional data
      set that focused on community service, was analyzed to investigate associations
      between the risk status of 4,306 adolescent students (50.2% female; 63.3%
      European American, M age = 15.9), their participation in community service, and
      their academic adjustment, behavioral problems, and civic knowledge. Because
      adolescents who participate in service differ from those who do not with respect
      to demographic characteristics, propensity score analyses were used to correct
      for potential selection bias in the examination of these relationships. Analyses
      tested competing theoretical models of service-protective versus compensatory
      among students at varying levels of risk, and suggested that service acts as a
      compensatory factor with respect to academic, behavioral, and civic outcomes.
      Propensity score analyses revealed patterns suggesting that, in some cases,
      students with certain demographic profiles that are themselves related to the
      likelihood of service participation may benefit from service participation more
      than others. Findings are discussed in terms of their significance for adolescent
      development, for planning service programs, and for educational policy.

PMID- 21744296
TI  - Impact of spatial filters during sensor selection in a visual P300 brain-computer
      interface.
AB  - A challenge in designing a Brain-Computer Interface (BCI) is the choice of the
      channels, e.g. the most relevant sensors. Although a setup with many sensors can
      be more efficient for the detection of Event-Related Potential (ERP) like the
      P300, it is relevant to consider only a low number of sensors for a commercial or
      clinical BCI application. Indeed, a reduced number of sensors can naturally
      increase the user comfort by reducing the time required for the installation of
      the EEG (electroencephalogram) cap and can decrease the price of the device. In
      this study, the influence of spatial filtering during the process of sensor
      selection is addressed. Two of them maximize the Signal to Signal-plus-Noise
      Ratio (SSNR) for the different sensor subsets while the third one maximizes the
      differences between the averaged P300 waveform and the non P300 waveform. We show
      that the locations of the most relevant sensors subsets for the detection of the
      P300 are highly dependent on the use of spatial filtering. Applied on data from
      20 healthy subjects, this study proves that subsets obtained where sensors are
      suppressed in relation to their individual SSNR are less efficient than when
      sensors are suppressed in relation to their contribution once the different
      selected sensors are combined for enhancing the signal. In other words, it
      highlights the difference between estimating the P300 projection on the scalp and
      evaluating the more efficient sensor subsets for a P300-BCI. Finally, this study
      explores the issue of channel commonality across subjects. The results support
      the conclusion that spatial filters during the sensor selection procedure allow
      selecting better sensors for a visual P300 Brain-Computer Interface.

PMID- 21744297
TI  - Pregnancy, alcohol intake, and intimate partner violence among men and women
      attending drinking establishments in a Cape Town, South Africa township.
AB  - The highest rates of fetal alcohol syndrome worldwide can be found in South
      Africa. Particularly in impoverished townships in the Western Cape, pregnant
      women live in environments where alcohol intake during pregnancy has become
      normalized and interpersonal violence (IPV) is reported at high rates. For the
      current study we sought to examine how pregnancy, for both men and women, is
      related to alcohol use behaviors and IPV. We surveyed 2,120 men and women
      attending drinking establishments in a township located in the Western Cape of
      South Africa. Among women 13.3% reported being pregnant, and among men 12.0%
      reported their partner pregnant. For pregnant women, 61% reported attending the
      bar that evening to drink alcohol and 26% reported both alcohol use and currently
      experiencing IPV. Daily or almost daily binge drinking was reported twice as
      often among pregnant women than non-pregnant women (8.4% vs. 4.2%). Men with
      pregnant partners reported the highest rates of hitting sex partners, forcing a
      partner to have sex, and being forced to have sex. High rates of alcohol
      frequency, consumption, binge drinking, consumption and binge drinking were
      reported across the entire sample. In general, experiencing and perpetrating IPV
      were associated with alcohol use among all participants except for men with
      pregnant partners. Alcohol use among pregnant women attending shebeens is
      alarmingly high. Moreover, alcohol use appears to be an important factor in
      understanding the relationship between IPV and pregnancy. Intensive, targeted,
      and effective interventions for both men and women are urgently needed to address
      high rates of drinking alcohol among pregnant women who attend drinking
      establishments.

PMID- 21744298
TI  - Leptin's regulation of obesity-induced cardiac extracellular matrix remodeling.
AB  - Obesity-induced remodeling of cardiac extracellular matrix (ECM) leads to
      myocardial fibrosis and ultimately diastolic dysfunction. Leptin, an adipocyte
      hormone, is emerging as a novel mechanistic link between obesity and heart
      diseases. Despite the known essential role of leptin in hepatic and renal
      fibrosis, the in vivo effects of leptin on cardiac ECM remodeling remain unclear.
      Our objective was to define the role of leptin as a key mediator of pro
      fibrogenic responses in the heart. In vitro administration of leptin to primary
      cardiofibroblasts resulted in significant stimulation of pro-collagen Ialpha ( 1
      ) and a decrease in pro-matrix metalloproteinase (MMP)-8, -9 and -13 gene
      expressions at 24 h. To study the in vivo pro-fibrotic effect, leptin was
      administrated to C57BL/6 and leptin-deficient ob/ob mice for 8 weeks. With
      exogenous leptin ob/ob mice displayed passive diastolic filling dysfunction,
      coincided with significant increase in myocardial collagen compared with ob/ob
      controls. We also observed a marked stimulation of pro-collagen IIIalpha ( 1 )
      and suppression of pro-MMP-8, TIMP-1 and -3 gene expressions in leptin-treated
      ob/ob mice. Our findings suggest pro-fibrotic effects of leptin in the heart,
      primarily through the predominance of collagen synthesis over degradation.

PMID- 21744299
TI  - Cellular level characterization of capillary regression in inflammatory
      angiogenesis using an in vivo corneal model.
AB  - In this study, we introduce a technique for repeated, microscopic observation of
      single regressing capillaries in vivo in inflamed murine corneas. Natural
      capillary regression was initiated by removal of inflammatory stimulus during an
      active pro-angiogenic phase, while the additional impact of anti-angiogenic
      treatment with triamcinolone or bevazicumab was investigated. Capillaries
      regressed naturally within 1 week and treatments did not further enhance the
      natural regression. Morphologically, early-phase regression was characterized by
      significant lumen narrowing and a significant reduction in CD11b+ myeloid cell
      infiltration of the extracellular matrix. By 1 week, vascular remodeling occurred
      concomitant with CD11b+CD68+KiM2R+ mature macrophage localization on capillary
      walls. Empty conduits without blood flow, positive for collagen IV and devoid of
      vascular endothelium and pericytes, were apparent in vivo and by 3 weeks were
      more numerous than perfused capillaries. By 3 weeks, macrophages aggregated
      around remaining perfused capillaries and were observed in apposition with
      degrading capillary segments. Abrupt termination of capillary sprouting in our
      regression model further revealed vascular endothelial abandonment of sprout tips
      and perfused capillary loop formation within a single angiogenic sprout, possibly
      as an intussusceptive response to cessation of the stimulus. Finally, we observed
      lumen constriction and macrophage localization on capillary walls in vivo in a
      clinical case of corneal capillary regression that paralleled findings in our
      murine model.

PMID- 21744301
TI  - Parametric study of horizontally vibrated grain packings: comparison between
      Discrete Element Method and experimental results.
AB  - Numerical and experimental studies have been undertaken to analyze three
      parameters controlling the compaction of granular media submitted to sinusoidal
      horizontal vibrations. We have characterized the influence of the dimensionless
      acceleration Gamma, the geometry of the container and the friction coefficients
      on the grain velocities and on the packing densities. Above a critical
      acceleration Gamma, the velocities increases with Gamma. For low values of Gamma,
      the surface layers are compacted, whereas the bottom layers remain at their
      initial density. For high values of Gamma, the bottom layers get compacted, the
      surface layers are fluidized so that the bulk dynamic and relaxed densities
      decreased. In the same way, the effect of the dimensions of the container and of
      the friction coefficients on the packing properties has been studied for given
      heights of sand, acceleration and frequency. It has been shown that the influence
      of the two last parameters is similar to that of acceleration. The numerical
      results given by the Discrete Element Method appear to be in good agreement with
      experimental results.

PMID- 21744302
TI  - Permeability of mixed soft and hard granular material: hydrogels as drainage
      modifiers.
AB  - We measure the flow of water through mixed packings of glass spheres and soft
      swellable hydrogel grains, at constant sample volume. Permeability values are
      obtained at constant sample volume and at porosities smaller than random close
      packing, for different glass bead diameters D and for variable gel grain diameter
      d, as controlled by the salinity of the water. The gel content is also varied. We
      find that the permeability decays exponentially in n(D/d )( b ), where n = N
      (gel)/N (glass) is the gel to glass bead number ratio and b is approximately 3.
      Therefore, flow properties are determined by the volume fraction of gel beads. A
      simple model based on the porosity of overlapping spheres is used to account for
      these observations.

PMID- 21744305
TI  - Roles of lineage-determining transcription factors in establishing open
      chromatin: lessons from high-throughput studies.
AB  - The interpretation of the regulatory information of the genome by sequence
      specific transcription factors lies at the heart of the specification of cellular
      identity and function. While most cells in a complex metazoan organism express
      hundreds of such transcription factors, the underlying mechanisms by which they
      ultimately achieve their functional locations within different cell types remain
      poorly understood. Here, we contrast various models of how cell type-specific
      binding patterns may arise using available evidence from ChIP-Seq experiments
      obtained in tractable developmental model systems, particularly the hematopoietic
      system. The data suggests a model whereby relatively small sets of lineage
      determining transcription factors jointly compete with nucleosomes to establish
      their cell type-specific binding patterns. These binding sites gain histone marks
      indicative of active cis-regulatory elements and define a large fraction of the
      enhancer-like regions differentiated cell types. The formation of these regions
      of open chromatin enables the recruitment of secondary transcription factors that
      contribute additional transcription regulatory functionality required for the
      cell type-appropriate expression of genes with both general and specialized
      cellular functions.

PMID- 21744306
TI  - Virus-like particles for antigen delivery at mucosal surfaces.
AB  - Virus-like particles are a new type of vaccine platform that presents an
      attractive alternative to more traditional live-attenuated or inactivated/subunit
      vaccines. Virus-like particles (VLP) are composed of viral structural proteins
      that assemble spontaneously in cells, mimicking the live virus without the
      possibility of replication. They are readily recognized by the immune system,
      inducing both humoral and cellular immune responses. Here we review the
      development of VLP as vaccine delivery systems at mucosal surfaces. We first
      summarize the current status of VLP vaccines in general, and then discuss their
      use in mucosal vaccination approaches for several viruses that enter the host via
      the urogenital, respiratory or gastrointestinal tract.

PMID- 21744308
TI  - Inhibitory effects of noscapine on dopamine biosynthesis in PC12 cells.

PMID- 21744309
TI  - Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol
      addiction as a reward deficit disorder.
AB  - Alcoholism can be defined by a compulsion to seek and take drug, loss of control
      in limiting intake, and the emergence of a negative emotional state when access
      to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and
      can be conceptualized as a disorder that includes a progression from impulsivity
      (positive reinforcement) to compulsivity (negative reinforcement). The compulsive
      drug seeking associated with alcoholism can be derived from multiple
      neuroadaptations, but the thesis argued here is that a key component involves the
      construct of negative reinforcement. Negative reinforcement is defined as drug
      taking that alleviates a negative emotional state. The negative emotional state
      that drives such negative reinforcement is hypothesized to derive from
      dysregulation of specific neurochemical elements involved in reward and stress
      within the basal forebrain structures involving the ventral striatum and extended
      amygdala, respectively. Specific neurochemical elements in these structures
      include not only decreases in reward neurotransmission, such as decreased
      dopamine and gamma-aminobutyric acid function in the ventral striatum, but also
      recruitment of brain stress systems, such as  corticotropin-releasing factor
      (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol,
      sufficient to produce dependence, increases reward thresholds, increases anxiety
      like responses, decreases dopamine system function, and increases extracellular
      levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists
      also block excessive drug intake produced by dependence. A brain stress response
      system is hypothesized to be activated by acute excessive drug intake, to be
      sensitized during repeated withdrawal, to persist into protracted abstinence, and
      to contribute to the compulsivity of alcoholism. Other components of brain stress
      systems in the extended amygdala that interact with CRF and that may contribute
      to the negative motivational state of withdrawal include norepinephrine,
      dynorphin, and neuropeptide Y. The combination of loss of reward function and
      recruitment of brain stress systems provides a powerful neurochemical basis for a
      negative emotional state that is responsible for the negative reinforcement
      driving, at least partially, the compulsivity of alcoholism.

PMID- 21744310
TI  - The therapeutic response of antiviral therapy in HBsAg-positive renal transplant
      recipients and a long-term follow-up.
AB  - BACKGROUND: Early prediction of lamivudine (LAM) response by individualized
      monitoring of serum HBV DNA like roadmap concept, and investigation of the
      outcome after LAM discontinuation in renal transplant recipients (RTRs) with
      chronic hepatitis B (CHB). METHODS: We conducted a study on 19 RTRs with HBV
      infection receiving LAM treatment for 2 years from 2004 to 2007. HBV DNA level
      was assessed at baseline, 12, 24, 52, and 104 weeks after treatment. Risk factors
      of tyrosine-methionine-aspartate-aspartate (YMDD) mutation on treatment and
      relapse rate of HBV after LAM discontinuation were analyzed. RESULTS: HBV DNA
      levels became undetectable in 32, 37, 63, and 53% of patients after 12, 24, 52,
      and 104 weeks of LAM treatment, respectively. Overall, three (16%) and five (33%)
      patients were detected with YMDD mutations at week 52 and 104, respectively. In
      the concept of roadmap, of the seven patients with inadequate virologic response
      (IAVR) at week 24, five had YMDD mutations. There was no significant association
      of YMDD mutations with age, gender, genotype, cirrhosis, HBeAg status, baseline
      HBV DNA, precore/core promoter mutations, and primary response, except IAVR at
      week 24 (P = 0.001). The relapse rate of HBV after LAM discontinuation was high
      (75%) during a median follow-up of 65 weeks. CONCLUSIONS: The rate of LAM
      resistance in RTRs is similar to immunocompetent CHB patients in a 2-year
      therapy. By roadmap concept, RTRs with IAVR require a change in therapy to
      prevent viral resistance. Relapse after LAM withdrawal is frequent. Long-term
      antiviral therapy is crucial for immunosuppressed patients.

PMID- 21744311
TI  - Sporadic late-onset nemaline myopathy in a patient with primary Sjogren's
      syndrome.

PMID- 21744312
TI  - Paeoniflorin protects against lipopolysaccharide-induced acute lung injury in
      mice by alleviating inflammatory cell infiltration and microvascular
      permeability.
AB  - OBJECTIVE: The present study aims to explore the effects of paeoniflorin (PF), a
      monoterpene glycoside isolated from the roots of Paeonia lactiflora Pallas, on
      acute lung injury (ALI) and the possible mechanisms. MATERIALS AND METHOD: ALI
      was induced in mice by an intratracheal instillation of lipopolysaccharide (LPS,
      1 mg/kg), and PF was injected intraperitoneally 30 min prior to LPS
      administration. After 24 h, lung water content, histology, microvascular
      permeability and proinflammatory cytokines in the bronchoaveolar lavage fluid
      were evaluated. RESULTS: It was shown that PF (50, 100 mg/kg) could alleviate LPS
      induced ALI, evidenced by reduced pulmonary edema, improved histological changes,
      and attenuated inflammatory cell accumulation in the interstitium and alveolar
      space as well as microvascular permeability. It also markedly down-regulated the
      expressions of proinflammatory cytokines interleukin (IL)-1beta and tumor
      necrosis factor (TNF)-alpha at both transcription and protein levels.
      Additionally, PF inhibited the phosphorylations of p38 MAP kinase (p38) and c-Jun
      NH2-terminal kinase (JNK) but not extracellular signal-regulated kinase (ERK),
      and prevented the activation of nuclear factor-kappa B (NF-kappaB) in the lung
      tissues. CONCLUSION: The findings suggest that PF is able to alleviate ALI, and
      the underlying mechanisms are probably attributed to decreasing the production of
      proinflammatory cytokines through down-regulation of the activation of p38, JNK
      and NF-kappaB pathways in lung tissues.

PMID- 21744313
TI  - Loss of expression of DNA mismatch repair proteins in aberrant crypt foci
      identified in vivo by magnifying colonoscopy in subjects with hereditary
      nonpolyposic and sporadic colon rectal cancer.
AB  - PURPOSE: The aims of this study are to characterize the frequency, density, and
      distribution of aberrant crypt foci (ACF) and its histological features and to
      determine the frequency of loss of expression of DNA mismatch repair (MMR)
      proteins of subjects with hereditary nonpolyposic colorectal cancer (HNPCC) and
      sporadic colon rectal cancer (CRC). METHODS: Patients with HNPCC, first-degree
      relatives of subjects with HNPCC, sporadic CRC, and average risk subjects of
      sporadic CRC were included prospectively. Total colonoscopy with chromoendoscopy
      using methylene blue 0.5% and magnification in the right colon (cecum and 20 cm
      of the ascending colon) and in the left colon (rectum) was performed; loss of
      expression of MLH1 and MSH2 was evaluated by immunohistochemistry in confirmed
      ACF. RESULTS: Fifty-two subjects were included. Thirty-eight of the 119 ACF
      detected by endoscopy were biopsied. In 14 of the 38 specimens (36.8%), ACF were
      confirmed by histology (Cohen's kappa, 0.44). In subjects with HNPCC, ACF were
      identified more frequently in the right segment of the colon than in the left
      (73.1% vs. 26%); in contrast, ACF predominated in the left segment of the colon
      (89.3% vs. 10.6%) in subjects with sporadic CRC. There was a loss of MLH1
      expression in ACF in subjects with HNPCC. CONCLUSIONS: In HNPCC, we found a
      greater density of ACF in the right colon, and in sporadic CRC, greater density
      in the left. ACF present loss in the expression of DNA MMR protein and can be
      used as an early marker in patients with a risk of HNPCC in whom carcinogenesis
      appears to be accelerated.

PMID- 21744314
TI  - The impact of age on effects of pre-hospital initiation of high bolus dose of
      tirofiban before primary angioplasty for ST-elevation myocardial infarction.
AB  - PURPOSE: Glycoprotein IIb/IIIa inhibitors are favourable in ST-elevation
      myocardial infarction (STEMI) patients, and the additional value of early pre
      hospital high bolus dose tirofiban has recently been established. The aim of this
      study was to determine the impact of age on myocardial reperfusion and clinical
      outcomes of pre-hospital administration of high bolus dose tirofiban. METHODS:
      This is a pre-specified sub-analysis of the multicentre, double-blind, placebo
      controlled, randomised On-TIME 2 trial and it's open label phase. The primary
      endpoint was mean residual ST segment deviation 1 h after primary PCI and was
      evaluated in three age groups. RESULTS: Of the 466 patients in the highest
      tertile (>=68 years), median age was 74.4 years (IQR 71.3-78.6 years) and 231
      (50%) were randomised to tirofiban. Mean residual ST segment deviation 1 h after
      PCI was significantly lower in elderly patients pre-treated with tirofiban
      compared to elderly patients without tirofiban pre-treatment (4.2 +/- 5.2 mm vs
      6.4 +/- 7.5 mm, p = 0.001). Furthermore, elderly patients pre-treated with
      tirofiban had a non-significantly higher rate of 30-day major or minor bleeding
      compared to elderly patients without tirofiban pre-treatment (14.2% vs 9.0%, p =
      0.088). 30-day net adverse clinical events in elderly patients with- or without
      tirofiban was not significantly different (11.9% vs 15.2%, p = 0.300).
      CONCLUSION: The effect of pre-hospital initiation of high bolus dose tirofiban on
      myocardial reperfusion, as determined by ST-segment resolution is highest in the
      elderly patients. However, this was associated with a trend towards more bleeding
      complications, resulting in a balanced clinical effect after 30-day follow-up.
      Future studies should evaluate whether the elderly STEMI patient may benefit from
      highly effective and safer antiplatelet therapy.

PMID- 21744315
TI  - Photoactivated green fluorescence emission by femtosecond oscillator from indole
      solutions.
AB  - We reported a novel femtosecond-laser-activated fluorescence emission from indole
      solutions upon excitation by the second harmonic wavelength of a femtosecond
      oscillator. A new absorption band around 400 nm and corresponding fluorescent
      band in the green domain were produced after the irradiation of femtosecond
      laser. This femtosecond-laser-activated luminescence process that allows the use
      of visible wavelength as a substitute for UV light to excite fluorescence from
      indole would extend applications based on indole chromophore. Furthermore, the
      photoactived emission can act as a fluorescence lifetime probe to measure the
      polarity in complex biological systems since it is polarity-sensitive. High
      performance liquid chromatography with fluorescence detector (HPLC-FLU) and high
      performance liquid chromatography with mass spectrometer (HPLC-MS) analysis
      demonstrate that the origin of the photoactivated fluorescence is new molecular
      species that generated in indole solution upon femtosecond laser irradiation.

PMID- 21744316
TI  - Epilepsy and argininosuccinic aciduria.
AB  - BACKGROUND: We have reviewed the occurrence of epilepsy in our patients with
      argininosuccinic aciduria (ASA) (OMIM 207900) and the possible relationship of
      late epilepsy to symptomatic seizures in the neonatal period, hyperammonaemia and
      treatments. METHODS: We retrospectively analysed 11 ASA patients (8 neonatal
      onset and 3 late onset), 6 of whom had developed epilepsy. RESULTS: Epilepsy in
      our sample was frequent (55 %). It developed after a seizure-free period from the
      onset of the metabolic disease and seizures were responsive to treatment in all
      cases. Arginine plasma levels were kept in the same range for the 2 groups of
      patients with and without epilepsy. CONCLUSIONS: Although epilepsy is reported to
      be common among patients with ASA, very few long-term follow-up studies are
      available. The pathophysiological mechanism of epileptogenesis remains unclear.
      Neither hyperammonaemia nor acute symptomatic seizures at birth seem to be
      predictive of late epilepsy. Excessive arginine dosages as a cause of epilepsy
      could be reasonably excluded since our 3 late onset patients developed epilepsy
      before the diagnosis of ASA, at a time when they were likely to be arginine
      deficient. Arginine deficiency may not be excluded as cause of epilepsy, but
      further studies are needed to define its role.

PMID- 21744317
TI  - Traditional Chinese medicine herbs - are they safe for psoriatic patients?
AB  - Although traditional Chinese medicine (TCM) relies on remedies of natural origin,
      its use is not always safe as it can have not only beneficial but also
      deleterious effects. Psoriatic patients, disappointed by conventional treatment
      and unaware of the potential side effects of TCM preparations, are increasingly
      reaching for non-traditional therapeutic methods. This review presents brief
      characteristics of selected Chinese herbs self-prescribed by psoriatic patients.
      It is important that dermatologists should be able to recognize any potential
      hazards connected with current or previous taking of these herbs by their
      patients.

PMID- 21744318
TI  - The rheological properties of blood and the risk of cardiovascular disease in
      patients with obstructive sleep apnea syndrome (OSAS).
AB  - Obstructive sleep apnea (OSA) is an important public health concern, which
      affects around 2-4% of the population. Left untreated, it causes a decrease not
      only in quality of life, but also of life expectancy. Despite the fact that
      knowledge about the mechanisms of development of cardiovascular disease in
      patients with OSA is still incomplete, observations confirm a relationship
      between sleep disordered breathing and the rheological properties of blood. One
      possible consequence of an increased incidence of cardiovascular disease may be a
      rise in mortality in OSA patients. Continuously improved research methods are
      allowing for an increasingly more accurate understanding of the significance of
      observed changes.

PMID- 21744319
TI  - Human umbilical cord expresses several vasoactive peptides involved in the local
      regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin,
      ANP, eNOS and iNOS.
AB  - Full-term human umbilical cord contains three blood vessels: two arteries coiled
      around a vein and surrounded by Wharton's jelly, a mucous tissue with few
      mesenchymal stromal cells and abundant extracellular matrix. Umbilical vessels
      lack innervations, thus endothelial cells must play a role in the control of
      blood flow. The aim of this study was to investigate in human umbilical cord the
      expression of five peptides that could be involved in the regulation of vascular
      tone: Orphanin FQ, Oxytocin, Atrial Natriuretic Peptide (ANP), endothelial Nitric
      Oxide Synthase (eNOS) and inducible Nitric Oxide Synthase (iNOS). The expression
      of these molecules in full-term human umbilical cord was investigated through
      immunohistochemistry and RT-PCR. Immunoreactivity for Orphanin FQ was detected in
      Wharton's jelly, vessel musculature and endothelium; Oxytocin, ANP and eNOS were
      expressed by the umbilical epithelium, Wharton's jelly and endothelium, whereas
      iNOS only by endothelial cells. RT-PCR analysis showed transcriptional expression
      of Oxytocin, ANP and eNOS mRNAs. The presence of Orphanin, Oxytocin, ANP, eNOS
      and iNOS proteins was identified in the human umbilical cord. mRNA expression for
      Oxytocin, ANP and eNOS suggest that these molecules are synthesized by umbilical
      cord cells themselves. The expression of these vasoactive molecules could be part
      of a general mechanism locally regulating vascular tone.

PMID- 21744320
TI  - Investigations of hippocampal astrocytes in lipopolysaccharide-preconditioned
      rats in the pilocarpine model of epilepsy.
AB  - The present paper is the first work to determine the effect of lipopolysaccharide
      (LPS) in the pilocarpine model of epilepsy on the morphology of rat hippocampal
      astrocytes in vivo. The study involved adult male Wistar rats, which 72 hours
      prior to administration of pilocarpine hydrochloride (PILO) were
      intraperitoneally (ip) preconditioned with LPS at a dose of 0.5 mg/kg b.w. The
      control animals were administered (ip) saline or LPS alone. The astrocytes in the
      control animals displayed characteristic stellate morphology. Examinations of the
      astrocytes were performed on days one, three and 21 of the pilocarpine model of
      epilepsy (i.e. in the acute, silent and chronic periods). The astrocytes of the
      CA1 and CA3 pyramidal layers of the hippocampus were observed and analyzed at the
      structural and ultrastructural levels. It was demonstrated that on days one and
      three, glial cells from both the nonpreconditioned and the LPS-preconditioned
      animals displayed similar reactive changes, manifesting themselves as swelling of
      cell bodies, glial processes, and astrocytosis. Moreover, reduction in cell
      organelles aggregated at one pole and the presence of vacuoles were observed. The
      most pronounced astrogliosis and cell swelling occurred on day 21. We conclude
      that LPS has no effect on the morphology of astrocytes in the pilocarpine model
      of epilepsy, unlike the results obtained by other authors in vitro.

PMID- 21744321
TI  - Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major
      influence on the cell cycle of Jurkat cells.
AB  - Benzalkonium chloride (BAK) is a cationic detergent with a very slow turnover.
      Because of its strong antibacterial activities, BAK is widely used especially in
      dentistry and ophthalmology. It is the most commonly used preservative in topical
      ophthalmic medications. Due to chronicity and widespread use of such treatments,
      BAK's side effects are of great importance. BAK toxicity for adherent cells,
      probably related to its pro-oxidative activities, is time- and dose-dependent.
      Although lymphocytes often infiltrate superficial eye tissues, the BAK influence
      on them is yet to be established. The aim of this study was to check BAK
      cytotoxicity on T lymphocytic Jurkat line cells and to verify the suggestion that
      BAK can induce G2M cell blocks. A dose- and time-dependent cytotoxic effect of
      BAK on lymphoid cells in relatively low concentrations was shown in this study.
      In lower concentrations, it shows a moderate apoptotic and minimal
      antiproliferative effect on Jurkat cells, while in higher concentrations it shows
      a rapid necrotic effect. No G2M cell blocks were observed. Our findings could
      suggest lymphoid dysfunction during intensive, prolonged topical BAK treatment,
      even at dosages relatively non-toxic to epithelial eye cells.

PMID- 21744322
TI  - A multiple marker analysis of apoptosis-associated protein expression in non
      small cell lung cancer in a Chinese population.
AB  - A failure to undergo apoptosis is widely thought to be an important event in
      cancer formation and progression. Although there have been many studies in vitro
      that provide evidence for this suggestion, the roles of apoptosis-associated
      proteins in cancer tissues in vivo are not as yet fully understood. Moreover,
      multiple marker analyses of apoptosis-associated protein expression in non-small
      cell lung cancer (NSCLC) tissues are scarce. In the present study, we investigate
      the expression of a group of apoptosis-associated proteins including bcl-2,
      caspase-3, fas, fas ligand (fasL) and survivin, and its clinical significance in
      NSCLC tissues using immunohistochemistry (IHC). Bcl-2 staining in cancer tissue
      cells was found in cytoplasm and the positive rate was 38.2% (29/76). Caspase-3
      staining was mainly seen in cytoplasm of cancer tissue cells (53.9% [41/76]) with
      a few cases of nuclear staining (6.6% [5/76]). Fas staining was seen in
      cytomembrane (15.8% [12/76]) and cytoplasm (42.1% [32/76]) of cancer tissue
      cells. Likewise, fasL also showed staining in cytoplasm (55.3% [42/76]) and
      cytomembrane (44.7% [34/76]) of cancer tissue cells. Survivin staining was seen
      in cytoplasm but not nuclear of cancer tissue cells and the positive rate was
      48.7% (37/76). Higher cytoplasm expression of bcl-2 was associated with large
      tumor size (>= 3 cm) in NSCLC (p < 0.05). Decreased cytoplasm expression of fas
      was associated with poor grade in NSCLC (p < 0.05). A negative correlation was
      found between bcl-2 and cytoplasm caspase-3 expression in NSCLC (p < 0.001). No
      separate expression of the apoptosis-associated proteins in NSCLC was linked to
      overall survival of patients (p > 0.05). Multiple marker analyses revealed
      caspase-3+/cytomembrane fasL- to be linked to better survival of patients with
      NSCLC (p < 0.05). These results indicate that apoptosis- -associated proteins may
      impact a variety of clinicopathological features of NSCLC and may co-operatively
      influence the prognosis of patients with this malignant tumor.

PMID- 21744323
TI  - Proinflammatory chemokine gene expression influences survival of patients with
      non-Hodgkin's lymphoma.
AB  - The migration, survival and proliferation of cells is the basis for all
      physiologic and pathologic processes in the human body. All these reactions are
      regulated by a complex chemokine network that guides lymphocytes homing,
      chemotaxis, adhesion and interplay between immunologic system response cells.
      Chemokines are also responsible for metastatic dissemination of cancers,
      including Hodgkin's and non-Hodgkin's lymphomas. The purpose of this study was to
      determine chemokine gene expression (CXCL8, CXCL10, CCL2, CCL3, CCL4 and CCL5) in
      lymphoma lymph nodes compared to their expression in reactive lymph nodes. We
      also analyzed the influence of chemokine gene expression on the survival of
      lymphoma patients. Chemokine gene expression was evaluated in 37 lymphoma lymph
      nodes and in 25 samples of reactive lymph nodes. Gene expression of chemokines
      CXCL8, CXCL10, CCL2, CCL3, CCL4 and CCL5 was measured using the PCR method.
      Statistical analysis was performed using CSS Statistica for Windows (version 7.0)
      software. Probability values < < 0.05 were considered statistically significant
      and those between 0.05 and 0.1 as indicative of a trend. We found lower CXCL8 and
      CXCL10 gene expression in lymphoma lymph nodes compared to reactive lymph nodes.
      In the cases of CCL2 and CCL3, expression in lymphomas was higher than in
      reactive lymph nodes. Patients with high expression of CCL2 and CXCL10 had
      shorter survival.

PMID- 21744324
TI  - Treatment of multiple myeloma patients with autologous stem cell transplantation 
      a fresh analysis.
AB  - Patients with multiple myeloma (MM) treated with conventional chemotherapy have
      an average survival of approximately three years. High dose chemotherapy followed
      by autologous stem cell transplantation (ASCT), first introduced in the mid
      1980s, is now considered the standard therapy for almost all patients with
      multiple myeloma, because it prolongs overall survival and disease free survival.
      Between November 1997 and October 2006, 122 patients with MM (58 females, 64
      males, median age 51.0 years [+/- 7.98] range: 30-66 years) were transplanted in
      the Department of Hematooncology and Bone Marrow Transplantation at the Medical
      University of Lublin: 47 patients were in complete remission or in unconfirmed
      complete remission, 66 patients were in partial remission, and nine had stable
      disease. Of these, there were 95 patients with IgG myeloma, 16 with IgA myeloma,
      one with IgG/IgA, one with IgM myeloma, five with non secretory type, two with
      solitary tumor and two with LCD myeloma. According to Durie-Salmon, 62 patients
      had stage III of the disease, 46 had stage II and four had stage I. Most patients
      (69/122) were transplanted after two or more cycles of chemotherapy, 48 patients
      were transplanted after one cycle of chemotherapy, one patient after surgery and
      rtg- -therapy and four patients had not been treated. In mobilisation procedure,
      the patients received a single infusion of cyclophosphamide (4-6 g/m(2)) or
      etoposide 1.6 g/m(2) followed by daily administration of G-CSF until the
      peripheral stem cells harvest. The number of median harvest sessions was 2.0 (+/-
      0.89) (range: 1-5). An average of 7.09 (+/- 33.28) * 106 CD34(+) cells/kg were
      collected from each patient (range: 1.8-111.0 * 106/kg). Conditioning regimen
      consisted of high dose melphalan 60-210 mg/m(2) without TBI. An average of 3.04
      (+/- 11.59) * 106 CD34+ cells/kg were transplanted to each patient. Fatal
      complications occured in four patients (treatment- -related mortality = 3.2%). In
      all patients there was regeneration of hematopoiesis. The median number of days
      for recovery to ANC > 0.5 * 109/l was 13 (+/- 4.69) (range: 10-38) and platelets
      recovery to > 50 * 109/l was 25 days (+/- 11.65) (range: 12-45). Median time of
      hospitalization was 22 days (+/- 7.14) (range: 14-50). Patients were evaluated on
      day 100 after transplantation: 74.9% achieved CR and nCR, 14.3% were in PR, 5.4%
      had SD and 5.4% had progressed. Median of OS was 45 months (+/- 30.67). OS at 3
      years was 84% and at 7-years 59%. Median PFS was 25 months (+/- 26.13). PFS at 3
      years was 68%, and at 7-years was 43%. At present (November 2009) 52 patients
      (42%) are still alive. High-dose chemotherapy followed by autologous stem cell
      transplantation is a valuable, well tolerated method of treatment for patients
      with MM that allows the achievement of long- -lasting survival.

PMID- 21744325
TI  - CD4+CD25+ and CD4+CD2+high regulatory T cells in disseminated and localized forms
      of allergic contact dermatitis: relation to specific cytokines.
AB  - The aim of this study was to evaluate regulatory T lymphocytes (Tregs) in the
      course of allergic contact dermatitis (ACD) and to elucidate the role of IL-10
      and TGF-beta in Tregs activity. Peripheral blood CD4(+)CD25(+) and
      CD4(+)CD25(high) cells were determined by flow cytometry in patients with acute
      disseminated ACD ('ad', n = 36), acute localized ACD ('al', n = 26), and
      disseminated ACD during remission ('rd', n = 27) as well as in controls (n = 22).
      Serum levels of cytokines were measured using ELISA. The mean percentage of
      CD4(+)CD25(+) and CD4(+)CD25(high) cells in patients with ad ACD was
      significantly higher than in controls (p < 0.01) and the remaining patients (p <
      0.05). Both cell populations were significantly elevated in persons with
      widespread skin lesions (p < 0.05). In ad patients the CD4(+)CD25(+) increased
      during three weeks of disease, although the significant increase of
      CD4(+)CD25(high) was noted only in the third week. Patients with ad ACD showed a
      significantly decreased serum level of TGF-beta1 as compared with controls and
      the remaining ACD patients. IL-10 level did not differ between all groups. The
      elevated population of CD4(+)CD25(high) cells in ad ACD patients, and its
      dependence on the extension of skin lesions, suggest a role of Tregs in
      regulating the course of ACD. The growing Tregs percentages may indicate their
      peripheral generation during ACD. The development of lesions despite an increased
      population of Tregs suggests their functional defect. The role of TGF-beta1 in
      the suppressive activity of Tregs cannot be excluded.

PMID- 21744326
TI  - Anaerobic bacteria colonizing the lower airways in lung cancer patients.
AB  - Anaerobes comprise most of the endogenous oropharyngeal microflora, and can cause
      infections of airways in lung cancer patients who are at high risk for
      respiratory tract infections. The aim of this study was to determine the
      frequency and species diversity of anaerobes in specimens from the lower airways
      of lung cancer patients. Sensitivity of the isolates to conventional
      antimicrobial agents used in anaerobe therapy was assessed. Respiratory
      secretions obtained by bronchoscopy from 30 lung cancer patients were cultured
      onto Wilkins-Chalgren agar in anaerobic conditions at 37 degrees C for 72-96
      hours. The isolates were identified using microtest Api 20A. The minimal
      inhibitory concentrations for penicillin G, amoxicillin/clavulanate,
      piperacillin/tazobactam, cefoxitin, imipenem, clindamycin, and metronidazole were
      determined by E-test. A total of 47 isolates of anaerobic bacteria were detected
      in 22 (73.3%) specimens. More than one species of anaerobe was found in 16
      (53.3%) samples. The most frequently isolated were Actinomyces spp. and
      Peptostreptococcus spp., followed by Eubacterium lentum, Veillonella parvula,
      Prevotella spp., Bacteroides spp., Lactobacillus jensenii. Among antibiotics used
      in the study amoxicillin/clavulanate and imipenem were the most active in vitro
      (0% and 2% resistant strains, respectively). The highest resistance rate was
      found for penicillin G and metronidazole (36% and 38% resistant strains,
      respectively). The results obtained confirm the need to conduct analyses of
      anaerobic microflora colonizing the lower respiratory tract in patients with lung
      cancer to monitor potential etiologic factors of airways infections, as well as
      to propose efficient, empirical therapy.

PMID- 21744327
TI  - JAK2 mutation status, hemostatic risk factors and thrombophilic factors in
      essential thrombocythemia (ET) patients.
AB  - The recently discovered JAK2 V617F point mutation, found in 50-60% of ET
      patients, has been reported to be associated with a higher risk of thrombotic
      events. In this study, we explored if JAK2 V617F mutation, or coexisting
      thrombophilic and hemostatic risk factors, contributed to these complications. We
      examined 32 patients with ET, and looked for pathogenetic JAK2 V617F mutation and
      prothrombotic genes mutations: factor V Leiden, prothrombin and MTHFR. We also
      evaluated plasma levels of fibrinogen, factors VIII and XII, AT, protein C,
      protein S and serum level of homocysteine. Urokinase concentration was assessed
      in patients' plasma as well as platelet lysates. There was no difference in the
      number of thrombotic complications between ET patients with and without JAK2
      mutation. However, we found a number of thrombophilic and hemostatic risk factors
      that could contribute to thrombotic complications in ET patients.

PMID- 21744328
TI  - Characteristics of weak base-induced vacuoles formed around individual acidic
      organelles.
AB  - We have previously found that the weak base 4-aminopyridine induces Brownian
      motion of acidic organelles around which vacuoles are formed, causing organelle
      traffic disorder in neurons. Our present study investigated the characteristics
      of vacuoles induced by weak bases (NH(4)Cl, aminopyridines, and chloroquine)
      using mouse cells. Individual vacuoles included acidic organelles identified by
      fluorescent protein expression. Mitochondria and actin filaments were extruded
      outside the vacuoles, composing the vacuole rim. Staining with amine-reactive
      fluorescence showed no protein/amino acid content in vacuoles. Thus, serous
      vacuolar contents are probably partitioned by viscous cytosol, other organelles,
      and cytoskeletons, but not membrane. The weak base (chloroquine) was
      immunochemically detected in intravacuolar organelles, but not in vacuoles. Early
      vacuolization was reversible, but long-term vacuolization caused cell death. The
      vacuolization and cell death were blocked by the vacuolar H(+)-ATPase inhibitor
      and Cl--free medium. Staining with LysoTracker or LysoSensor indicated that
      intravacuolar organelles were strongly acidic and vacuoles were slightly acidic.
      This suggests that vacuolization is caused by accumulation of weak base and H(+)
      in acidic organelles, driven by vacuolar H(+)-ATPase associated with Cl(-)
      entering, and probably by subsequent extrusion of H(+) and water from organelles
      to the surrounding cytoplasm.

PMID- 21744329
TI  - Assessment of the levels of nitric oxide (NO) and cytokines (IL-5, IL-6, IL-13,
      TNF, IFN-gamma) in giardiosis.
AB  - The current study aims to determine the involvement of cellular responses in
      combating Giardia intestinalis invasion. The study group consisted of 44 women
      and 18 men, aged 18-72 years, infected with G. intestinalis. The diagnosis was
      established based on laboratory investigations (examination of stool, choloscopy,
      GSA-65). Blood for analysis was collected before antiparasitic treatment and two
      weeks after treatment termination. The control group consisted of 22 women and 18
      men aged 20-45 years. The serum concentrations of IL-5, IL-6, IL-13, TNF, IFN-g
      were assayed using a set of Quantikine human. The concentrations of NO in the
      serum were determined using a set of Total Nitric Oxide Assay. Patients infected
      with G. intestinalis showed a statistically significant increase in the levels of
      NO, IFN-g and IL-13. Even the antiparasitic treatment applied did not reduce the
      levels of these parameters and only caused a rise in IL-6. Our study showed a
      lack of acute inflammatory state in the course of G. intestinalis infection.

PMID- 21744330
TI  - Microtubule heterogeneity of Ornithogalum umbellatum ovary epidermal cells: non
      stable cortical microtubules and stable lipotubuloid microtubules.
AB  - Lipotubuloids, structures containing lipid bodies and microtubules, are described
      in ovary epidermal cells of Ornithogalum umbellatum. Microtubules of
      lipotubuloids can be fixed in electron microscope fixative containing only
      buffered OsO(4) or in glutaraldehyde with OsO(4) post-fixation, or in a mixture
      of OsO(4) and glutaraldehyde. None of these substances fixes cortical
      microtubules of ovary epidermis of this plant which is characterized by dynamic
      longitudinal growth. However, cortical microtubules can be fixed with cold
      methanol according immunocytological methods with the use of beta-tubulin
      antibodies and fluorescein. The existence of cortical microtubules has also been
      evidenced by EM observations solely after the use of taxol, microtubule
      stabilizer, and fixation in a glutaraldehyde/OsO(4) mixture. These microtubules
      mostly lie transversely, sometimes obliquely, and rarely parallel to the cell
      axis. Staining, using Ruthenium Red and silver hexamine, has revealed that
      lipotubuloid microtubules surface is covered with polysaccharides. The
      presumption has been made that the presence of a polysaccharide layer enhances
      the stability of lipotubuloid microtubules.

PMID- 21744331
TI  - Caveolin-1, caveolin-3 and VEGF expression in the masticatory muscles of mdx
      mice.
AB  - Duchenne muscular dystrophy (DMD) and murine X-linked muscular dystrophy (mdx),
      its murine model, are characterized by muscle damage and muscle weakness
      associated with inflammation and new vessel formation. Caveolins, dystrophin
      associated proteins, are involved in the pathogenesis of DMD, because increased
      numbers of caveolae are found in DMD and mdx hindlimb muscles. Caveolae influence
      angiogenesis due to their content of vascular endothelial growth factor (VEGF)
      receptors. Orofacial muscles in mdx mice undergo muscle necrosis followed by
      muscle regeneration. To ascertain the role of caveolins and VEGF in the
      pathogenesis of dystrophic masticatory muscles, we examined the expression of
      caveolin-1 (cav-1), caveolin-3 (cav-3) and VEGF in control and mdx mice. In mdx
      masticatory muscles, no changes in transcript and protein levels of VEGF were
      found, whereas cav-1 and cav-3 expression was increased. Using
      immunohistochemistry, a strong sarcolemmal staining of caveolin-3 in regenerated
      muscle fibers was found. Furthermore, immunohistochemistry with the caveolin-1
      antibody showed an increase in the amount of blood vessels in areas with
      regenerating muscle fibers. Dystrophic masticatory muscles showed changes
      comparable to those of hindlimb muscles in the expression of cav-1 and cav-3. The
      angiogenesis seems to be unaffected in the jaw muscles of mdx mice. We speculate
      that the increased caveolin expression could cause extensive and efficient muscle
      regeneration.

PMID- 21744332
TI  - The immunohistochemical demonstration of parafollicular cells and evaluation of
      calcium-phosphate balance in patients with thyroid hemiagenesis.
AB  - Thyroid hemiagenesis (TH) is characterized by the congenital absence of one
      thyroid lobe. The aim of this study was to evaluate the calcium-phosphate balance
      in TH. Twenty patients with TH and 20 controls with a bilobed thyroid were
      studied. Serum concentrations of total calcium, parathormon and calcitonin were
      measured. Additionally, the immunohistochemical expression of calcitonin,
      chromogranin A (chA), neuron-specific enolase (NSE) and calcitonin gene-related
      peptide (CGRP) was evaluated in surgical specimens from patients with TH and
      controls. There were no significant differences in biochemical parameters between
      TH and controls. Positive staining for calcitonin was demonstrated in 3/8 thyroid
      sections from three patients with TH, but only in 2/33 sections from four
      controls (p < 0.005). All sections from patients with TH positive for calcitonin
      also expressed chA, NSE and CGRP. Two sections from controls positive for
      calcitonin presented an additionally positive reaction for chA, and one of them
      also for NSE. None presented positive staining for CGRP. Of three TH sections, in
      one, hyperplasia of C cells of medium grade, and in another hyperplasia of C
      cells of high grade, could be detected. In the controls, hyperplasia of C cells
      of low and medium grade was observed. TH was associated with slightly enhanced C
      cells hyperplasia compared to controls, which might indicate compensatory
      proliferation. However, the calcium-phosphate balance does not seem to be
      significantly affected.

PMID- 21744333
TI  - Glycopattern analysis and structure of the egg extra-cellular matrix in the
      Apennine yellow-bellied toad, Bombina pachypus (Anura: Bombinatoridae).
AB  - We studied the glycopatterns and ultrastructure of the extra-cellular matrix
      (ECM) of the egg of the Apennine yellow-bellied toad Bombina pachypus, by light
      and electron microscopy in order to determine structure, chemical composition and
      function. Histochemical techniques in light microscopy included PAS and Alcian
      Blue pH 2.5 and 1.0, performed also after beta-elimination. Lectin-binding was
      tested with nine lectins (AAA, ConA, DBA, HPA, LTA, PNA, SBA, UEA-I, WGA). An
      inner fertilization envelope (FE) and five jelly layers (J1-J5) were observed,
      differing in histochemical staining, lectin binding and ultrastructure. Most
      glycans were O-linked, with many glucosamylated and fucosylated residues. The
      fertilization envelope presented a perivitelline space and a fertilization layer,
      with mostly neutral glycans. The jelly layers consisted of fibers and granules,
      whose number and orientation differed between layers. Fibers were densely packed
      in J(1) and J(4) layers, whereas a looser arrangement was observed in the other
      layers. Jelly-layer glycans were mostly acidic and particularly abundant in the
      J(1) and J(4) layers. In the J(1), J(2) and J(5) layers, neutral, N-linked
      glycans were also observed. Mannosylated and/or glucosylated as well as
      galactosyl/galactosaminylated residues were more abundant in the outer layers.
      Many microorganisms were observed in the J(5) layer. We believe that, apart from
      their functions in the fertilization process, acidic and fucosylated glycans
      could act as a barrier against pathogen penetration.

PMID- 21744334
TI  - Selective gene expression profiling of mTOR-associated tumor suppressor and
      oncogenes in ovarian cancer.
AB  - The aim of this study was to selectively profile the activation status of
      mammalian target of rapamycin (mTOR)-associated oncogenes and tumor suppressor
      genes (TSGs) in ovarian cancer specimens, healthy ovaries and benign ovarian
      tumors, including endometrial cysts. We used a novel type of microfluidic gene
      array to examine the expression of 15 human tumor suppressors and oncogenes in
      ovarian cancer specimens of 53 patients, benign ovarian cysts of 29 women
      (endometrial and simple) and 11 healthy ovaries of individuals in whom the
      material was obtained during total hysterectomies performed because of fibroid
      changes. The array was custom-designed to include the following genes: NF1, RHEB,
      mTOR1, AKT-1, PTEN, TSC1, TSC2, KRAS, RPS6KB1, 4EBP1, TP53, EIF4E, STK11, PIK3CA
      and BECN1. Confirmatory immunohistochemical detection was performed for a group
      of selected proteins. Particularly significant differences were observed as to
      the expression of PTEN (p < 0.0001), TP53 (p = 0.0003), PIK3CA (p = 0.0003) and
      BECN1 (p = 0.0014) which were shown to be downregulated in cancer patients when
      compared to healthy ovaries and benign ovarian cysts (endometrial and simple).
      These markers did not show association with grade or stage of the tumor.
      Immunohistochemistry showed that PTEN, TP53, PIK3CA and BECN1 proteins are
      expressed in ovarian cancer. Our results indicate that there are significant
      differences in the expression of some of the mTOR-related tumor suppressors and
      oncogenes which could be associated with the pathogenesis of ovarian cancer.

PMID- 21744335
TI  - Expression of glucocorticoid receptor and glucose transporter-1 during placental
      development in the diabetic rat.
AB  - In various tissues, glucocorticoids (GCs) are known to downregulate glucose
      transport systems; however, their effects on glucose transporters (GLUTs) in the
      placenta of a diabetic rat are unknown. Glucocorticoid hormone action within the
      cell is regulated by the glucocorticoid receptor (GR). Thus, this study was
      designed to investigate the relationship between GR and glucose transporter
      expression in the placenta of the diabetic rat. Our immunohistochemical results
      indicated that GR and glucose transporter protein 1 (GLUT 1) are expressed
      ubiquitously in the trophoblast and endothelial cells of the labyrinthine zone,
      where maternal fetal transport takes place in the rat placenta. Expression of GR
      in the junctional zone of the rat placenta was detected in giant cells, and in
      some spongiotrophoblast cells, but not in the glycogen cells. GLUT 1 was present,
      especially in glycogen cells during early pregnancy, and in the
      spongiotrophoblast cells of the junctional zone during late pregnancy. Amounts of
      GR and GLUT 1 protein were increased towards the end of gestation both in the
      control and the diabetic placenta. However, at days 17 and 19 of gestation, only
      the placental GR protein was significantly increased in the streptozotocin
      induced diabetic rats compared to control rats. Diabetes led to a significant
      decrease in placental weight at gestation day 15. In contrast, at gestational
      days 17 and 21, the weights of the diabetic placenta were significantly increased
      as compared with the controls. Moreover, diabetes induced fetus intrauterine
      growth retardation at gestational days 13, 17 and 21. In conclusion, the
      localization pattern of GR and GLUT 1 proteins in the same cell types led us to
      believe that there might be a relationship between GR and GLUT 1 expressions at
      the cellular level. GLUT 1 does not play a pivotal role in diabetic pregnancies.
      However, placental growth abnormalities during diabetic pregnancy may be related
      to the amount of GR.

PMID- 21744336
TI  - Involucrin, but not filaggrin and Kdap mRNA, expression is downregulated in 3-D
      cultures of intact rat hair bulbs after calcium stimulation.
AB  - The hair follicle consists of several distinctive epidermal cell layers. The hair
      root, which undergoes keratinization, is surrounded by two sheaths: the inner
      root sheath (IRS) and the outer root sheath (ORS). The ORS is continuous with the
      basal layer of the epidermis. Its cells do not keratinize in situ, unlike IRS. We
      have previously demonstrated that keratinization of the ORS was prevented by
      contact with the IRS in hair follicle mid-segments (i.e. fragments dissected from
      skin at the level above the hair bulb and below the opening of the sebaceous
      gland duct) cultured on agarose layer. The purpose of this study was to determine
      whether the same applies to the hair bulb. After isolation, intact bulbs or hair
      bulb-derived cells were incubated in suspension in a low or high calcium medium.
      The level of mRNA for differentiation markers: involucrin, filaggrin,
      keratinocyte differentiation associated protein and trichohyalin, was studied by
      RealTime PCR. We observed increased Ca(2+) upregulated expression of involucrin,
      filaggrin, trichohyalin and Kdap in cultures of bulb-derived cells, but in hair
      bulbs downregulation of involucrin and trichohyalin was observed. We concluded
      that the inner root sheath exerts an inhibitory effect on the expression of
      involucrin and trichohyalin already in the hair bulbs. The observation that
      downregulation of involucrin expression under Ca(2+) influence occurs both in
      hair bulb and midsegments could simplify future experiments, since their
      separation does not seem to be necessary.

PMID- 21744337
TI  - Expression of the transcription factor regulatory factor X1 in the mouse brain.
AB  - Limited information indicates that the regulatory factor X1 (RFX1), the prototype
      member of the transcription factor RFX family, may play a role in the central
      nervous system. Our recent study showed that knockout of the Rfx1 gene led to
      early embryonic death. In the present study, we showed that heterozygous Rfx1(+/
      ) mice were fertile and grew normally. An abundant amount of RFX1 proteins were
      expressed in the olfactory bulb, hippocampus and cerebral cortex as detected by
      beta-galactosidase staining (the gene knockout vector contained a coding region
      for beta-galactosidase) and immunofluorescent staining with an anti-RFX1
      antibody. RFX1 positive immunostaining was mainly in the nuclei of neurons and
      microglial cells and was absent from the astrocytes of mouse brains. The
      heterozygous Rfx1(+/-) mice expressed RFX1 mRNA and proteins at a level similar
      to that in the wild-type mice in the olfactory bulb and hippocampus. The
      expression level of RFX1 proteins was similar in the brains of mice ranging from
      15 day old embryos to four month old adults. Our results suggest a significant
      expression of RFX1 proteins in the mammalian brain. This expression is cell-type
      and brain-region specific and may take a random monoallelic expression pattern.

PMID- 21744338
TI  - Gaucher disease diagnosed after bone marrow trephine biopsy - a report of two
      cases.
AB  - The hematologist is at the forefront of specialists to whom patients with Gaucher
      disease present because of cytopenia and hepatosplenomegaly. Usually, patients
      with such symptoms have undergone trephine biopsy. We present the cases of two
      patients in whom Gaucher disease was suspected because of the discovery of
      Gaucher cells in trephine biopsy, and subsequently confirmed via enzymatic and
      molecular investigations.

PMID- 21744339
TI  - Inflammatory bowel disease - is there something new in the immunological
      background?
AB  - In the present paper we correlate clinical data, as well as histopathological,
      immunohistochemical and molecular biology methods, with the occurrence of both
      forms of inflammatory bowel disease (IBD) i.e. ulcerative colitis and Crohn's
      disease. We found that patients with a history of Epstein-Barr virus (EBV) or
      cytomegalovirus (CMV) infections, as well as steroid treatment, had increased
      susceptibility to the development of IBD. The diagnosis of IBD was confirmed by
      histopathology. Previous infections by EBV and CMV, as well as M. tuberculosis,
      were proved by PCR-based techniques and in situ hybridization. We found PCR
      proved latent viral infections in 30-50% of the IBD patients we studied. However,
      we were unable to prove the presence of viral antigens by immunohistochemistry
      for EBV or CMV. We found positive correlations between the presence of anti-CMV
      IgG, as well as PCR-positive results for M. tuberculosis with an ulcerative
      colitis diagnosis. Additionally, up to 80% of IBD patients used steroids, which
      was found to be correlated with a diagnosis of Crohn's disease. Our data may
      support the theory that IBD could be related to previous viral infections and the
      use of steroids.

PMID- 21744340
TI  - Identification of abrogated pathways in fallopian tube epithelium from BRCA1
      mutation carriers.
AB  - The discovery of occult invasive and intra-epithelial tubal carcinomas in BRCA1
      mutation carriers undergoing prophylactic surgery has implicated the fallopian
      tube epithelium as the source of serous cancer. However, little is known of the
      early molecular events of serous oncogenesis, or why cancers in BRCA1 mutation
      carriers are found preferentially in tissues which are responsive to reproductive
      hormones. We hypothesize that molecular alterations present in morphologically
      normal tubal epithelium from BRCA1 heterozygotes reflect the earliest events in
      serous carcinogenesis and may be markers of increased cancer risk as well as
      targets for risk reduction. Genetic profiling of microdissected tubal epithelium
      from histologically normal BRCA1 mutation carriers and controls was performed. We
      sought to define a signature which differentiated BRCA1 mutant tubal epithelium
      from women with low risk of developing ovarian cancer. Molecular differences
      between the follicular and luteal phases were prominent and, by using filtering
      techniques and a two-way ANOVA without a False Discovery Rate correction, we
      identified 440 probe sets with a more than two-fold change in gene expression
      related to BRCA1 mutation status. Using gene ontology and known associations to
      cancer pathways, we selected five genes for further analysis by qPCR and
      immunohistochemistry, and were able to demonstrate statistically significant
      differentiation of BRCA1 and control cases in an independent set of cases. The
      altered expression profiles in histologically normal tubal epithelium from BRCA1
      heterozygotes suggest that these cells may respond differently to
      microenvironmental stresses.

PMID- 21744341
TI  - Discovery of a novel tumour metastasis-promoting gene, NVM-1.
AB  - We have previously reported that over-expression of a panel of 119 genes
      correlates with the metastatic potential of pancreatic carcinoma cells. We sought
      to identify and functionally characterize candidate tumour metastasis promoting
      genes among this library using a secondary phenotype-assisted screen. Here we
      report the discovery of the metastasis-promoting function of a hitherto not
      characterized gene located on chromosome 14 (ORF138), which we have named 'novel
      metastasis-promoting gene 1' (NVM-1). The NVM-1 transcript is extensively
      alternatively spliced, is expressed endogenously in a number of different
      tissues, and is strongly over-expressed at the protein level in a variety of
      human tumour types. Importantly, NVM-1 expression stimulates the migratory and
      invasive behaviour of tumour cells and promotes metastasis formation in
      experimental animals in vivo. Up-regulation of FMNL2 and MT1E and down-regulation
      of TIMP4 and MHC-I is observed as a consequence of NVM-1 expression. Together
      these data identify NVM-1 as a gene that is functionally involved in tumour
      metastasis, and suggest that NVM-1 may constitute a promising therapeutic target
      for inhibition of tumour metastasis.

PMID- 21744342
TI  - A DeltaRaf1-ER-inducible oncogenic zebrafish liver cell model identifies
      hepatocellular carcinoma signatures.
AB  - Although the underlying molecular mechanism of hepatocellular carcinoma remains
      unclear, signalling pathways essential in cell survival and growth are altered,
      including the Raf-MEK-MAPK pathway. This pathway can be activated by hepatitis B
      or C virus infections and the ectopic expression of the Raf-1 oncogene is
      frequently seen in hepatocellular carcinomas. In addition, the Raf-MEK-MAPK
      pathway was also shown to be deregulated in zebrafish liver tumours. Based on the
      genetic conservation between zebrafish and human liver tumours, the zebrafish was
      used as an animal model to better understand the molecular basis of
      hepatocellular carcinoma. Here we establish an inducible oncogenic zebrafish cell
      model, in which oncogenic human Raf-1(DeltaRaf1) can be post-transcriptionally
      activated in zebrafish liver cells by administration of 4-hydroxytamoxifen (4HT).
      The DeltaRaf1 activation resulted in the hyperactivation of the zebrafish MEK-ERK
      cascade, promoted cell growth and proliferation, and inhibited apoptosis. The
      mitogenic transformation of the ZFL-DeltaRaf1-ER cells was confirmed by in vivo
      allo-transplantation and in silico microarray analyses. Gene expression profiling
      of cells treated with 4HT and a MEK-inhibitor identified a Raf-MEK-dependent
      signature set. This transcriptome response was compared to zebrafish and human
      liver cancer transcriptomes. We identified, and validated by quantitative PCR, a
      set of genes transcriptionally regulated by hyperactive MAPK signalling in ZFL
      DeltaRaf1-ER cells, zebrafish liver tumours and human liver tumours, suggesting
      that the in vitro zebrafish liver cell model can be used for further study of the
      molecular basis of human hepatocellular carcinoma. The molecular targeting of the
      commonly regulated hepatocellular carcinoma genes using the ZFL-DeltaRaf1-ER cell
      model can be applied for high-throughput preclinical target discovery.

PMID- 21744343
TI  - The human urothelium consists of multiple clonal units, each maintained by a stem
      cell.
AB  - Little is known about the clonal architecture of human urothelium. It is likely
      that urothelial stem cells reside within the basal epithelial layer, yet lineage
      tracing from a single stem cell as a means to show the presence of a urothelial
      stem cell has never been performed. Here, we identify clonally related cell areas
      within human bladder mucosa in order to visualize epithelial fields maintained by
      a single founder/stem cell. Sixteen frozen cystectomy specimens were serially
      sectioned. Patches of cells deficient for the mitochondrially encoded enzyme
      cytochrome c oxidase (CCO) were identified using dual-colour enzyme
      histochemistry. To show that these patches represent clonal proliferations, small
      CCO-proficient and -deficient areas were individually laser-capture
      microdissected and the entire mitochondrial genome (mtDNA) in each area was PCR
      amplified and sequenced to identify mtDNA mutations. Immunohistochemistry was
      performed for the different cell layers of the urothelium and adjacent
      mesenchyme. CCO-deficient patches could be observed in normal urothelium of all
      cystectomy specimens. The two-dimensional length of these negative patches varied
      from 2-3 cells (about 30 um) to 4.7 mm. Each cell area within a CCO-deficient
      patch contained an identical somatic mtDNA mutation, indicating that the patch
      was a clonal unit. Patches contained all the mature cell differentiation stages
      present in the urothelium, suggesting the presence of a stem cell. Our results
      demonstrate that the normal mucosa of human bladder contains stem cell-derived
      clonal units that actively replenish the urothelium during ageing. The size of
      the clonal unit attributable to each stem cell was broadly distributed,
      suggesting replacement of one stem cell clone by another.

PMID- 21744344
TI  - Haem oxygenase-1 dictates intrauterine fetal survival in mice via carbon
      monoxide.
AB  - Pregnancy establishment implies the existence of a highly vascularized and
      transient organ, the placenta, which ensures oxygen supply to the fetus via
      haemoproteins. Haem metabolism, including its catabolism by haem oxygenase-1 (HO
      1), should be of importance in maintaining the homeostasis of haemoproteins and
      controlling the deleterious effects associated with haem release from maternal or
      fetal haemoglobins, thus ensuring placental function and fetal development. We
      demonstrate that HO-1 expression is essential to promote placental function and
      fetal development, thus determining the success of pregnancy. Hmox1 deletion in
      mice has pathological consequences for pregnancy, namely suboptimal placentation
      followed by intrauterine fetal growth restriction (IUGR) and fetal lethality.
      These pathological effects can be mimicked by administration of exogenous haem in
      wild-type mice. Fetal and maternal HO-1 is required to prevent post-implantation
      fetal loss through a mechanism that acts independently of maternal adaptive
      immunity and hormones. The protective HO-1 effects on placentation and fetal
      growth can be mimicked by the exogenous administration of carbon monoxide (CO), a
      product of haem catabolism by HO-1 that restores placentation and fetal growth.
      In a clinical relevant model of IUGR, CO reduces the levels of free haem in
      circulation and prevents fetal death. We unravel a novel physiological role for
      HO-1/CO in sustaining pregnancy which aids in understanding the biology of
      pregnancy and reveals a promising therapeutic application in the treatment of
      pregnancy pathologies.

PMID- 21744345
TI  - Tumor size and presence of calcifications on ultrasonography are pre-operative
      predictors of lymph node metastases in patients with papillary thyroid cancer.
AB  - BACKGROUND AND OBJECTIVES: Lymph node metastases in papillary thyroid cancer
      (PTC) are common and their presence can significantly alter the treatment for
      patients with PTC. We therefore sought to identify pre-operative predictors of
      lymph node metastases in patients with PTC. METHODS: A thyroid tumor database was
      queried to identify patients with a pre-operative diagnosis of PTC and underwent
      thyroidectomy between January 2006 and August 2009. One hundred and three
      patients who had a pre-operative ultrasound and had lymph nodes surgically
      resected were identified. Clinical factors and tumor ultrasound characteristics
      were recorded. The pre-operative ultrasound results, type of operation, and final
      pathology results were also recorded. RESULTS: Of the 103 patients, 74 (72%) were
      women and 29 (28%) were men with an age range of 15-78 years (median age of 43).
      Of the ultrasound characteristics evaluated only calcifications (P = 0.007) and
      size (P = 0.003) were statistically associated with positive cervical lymph
      nodes. None of the other demographic or clinical factors were significantly
      associated with lymph node metastases. CONCLUSIONS: Thyroid nodule size and
      presence of calcifications on ultrasound were found to have a statistically
      significant association with lymph node metastases in patients with PTC. This
      information could be used to guide the surgical management of these patients.

PMID- 21744346
TI  - The effect of ischemic preconditioning on redox status during liver resections-
      randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Portal clamping during liver resection decreases
      intraoperative blood loss, but causes ischemic-reperfusion (I-R) injury.
      Intermittent portal clamping (IPC) and ischemic preconditioning (IP) decreased I
      R injury in animal models. Most of the human studies about IP excluded cirrhotic
      patients, whose liver is more vulnerable to I-R injury. The effect of IP and IPC
      during extended liver resection was investigated in this randomized controlled
      trial, with special respect to cirrhotic patients. METHODS: One hundred sixty
      patients (100 normal liver, 60 cirrhotic) undergoing major liver resection were
      randomized to receive IPC (15  min ischemia, 5  min reperfusion), or IP (10  min
      ischemia, 10  min reperfusion). Serum oxygen-derived free radicals (ODFR) and
      antioxidant concentrations (preoperative, after reperfusion and 7th postoperative
      day), such as "conventional" liver tests (preoperative, 1st, 3rd, and 7th
      postoperative day) were measured. RESULTS: IP resulted in significantly lower
      peak ODFR, AST, ALT, and bilirubin levels after liver resection than IPC (P <
      0.05). The level of serum antioxidants after reperfusion was significantly higher
      in IP than in IPC groups (P < 0.05). In cirrhotic patients without IP none of
      these values normalized until the 7th postoperative day. CONCLUSIONS: Ischemic
      preconditioning--especially in patients with liver cirrhosis--is a suitable
      method to decrease the I-R injury of the liver.

PMID- 21744347
TI  - Intra-lesional interleukin-2 for the treatment of in-transit melanoma.
AB  - PURPOSE: To investigate the role of intra-lesional interleukin-2 (IL-2) injection
      for treatment of in-transit melanoma metastases. METHODS: Consecutive patients
      with in-transit metastases were treated with intra-lesional IL-2 injections. Two
      independent observers evaluated response to treatment using the Response
      Evaluation Criteria in Solid Tumors (RECIST) criteria. A blinded pathologist
      confirmed clinical response with post-treatment biopsies. RESULTS: Thirty-nine
      patients were included. Patients received biweekly IL-2 injections. At each
      treatment session, a mean of 2.08 ml (5 u/ml) of IL-2 were distributed amongst a
      mean of 12 (range 1-57) in-transit lesions. Patients were followed for an average
      of 30.4 months (range 2.2-66.6 months). The overall patient response rate was
      82%. A complete response was obtained in 20 patients (51%), a partial response in
      12 (31%), and no response in seven (18%). Of the 629 in-transit metastases, 479
      (76%) completely resolved. Complete responders had a significant in transit-free
      (P = 0.0005) and an overall (P = 0.012) survival advantage compared with partial
      responders. CONCLUSIONS: The treatment of in-transit metastatic melanoma with
      intra-lesional IL-2 resulted in a 76% percent clearance of lesions. Complete
      response is associated with superior in transit-free and overall survival when
      compared with partial response.

PMID- 21744348
TI  - The symptom-to-diagnosis delay in soft tissue sarcoma influence the overall
      survival and the development of distant metastasis.
AB  - BACKGROUND: There are very few reports regarding the impact of the symptom that
      caused patients to consult a doctor and the symptom-to-diagnosis delay on
      survival for soft tissue sarcoma patients. The purpose of this study is to
      investigate whether symptom-treatment delay are associated with the presence of
      metastasis at diagnosis, overall survival and distant metastasis-free survival in
      primary soft tissue sarcomas. METHODS: This study retrospectively reviewed the
      medical records of 100 newly diagnosed patients with primary soft tissue sarcoma
      referred to our hospital. RESULTS: Eighteen of 100 sarcoma patients had distant
      metastases at diagnosis. A multivariate logistic regression analysis revealed
      that tumor size, tumor site, and the interval between the onset of the initial
      symptom and the first consultation to our hospital were all found to be
      significant predictors of distant metastases at diagnosis. The patients (n = 48)
      who were treated within the first 6 months from the onset of the initial symptom
      showed significantly better cumulative overall survival rate than those (n = 34)
      who were diagnosed more than 6 months (5-years: 77.0% vs. 59.7%). CONCLUSION:
      These results suggest that a shorter delay may have a beneficial effect on
      treatment options and outcome, improving survival in some sarcoma patients.

PMID- 21744349
TI  - Quantitative comparison of surgical margin histology following excision with
      traditional electrosurgery and a low-thermal-injury dissection device.
AB  - BACKGROUND: This study is the first to examine in vivo the effect of thermal
      injury in breast conservation pathology in a direct comparison of traditional
      electrosurgery and an alternative low-thermal-injury device. METHODS: A
      prospective study of 20 consecutive subjects with biopsy-proven invasive ductal
      carcinoma (IDC) tumors 1 cm was conducted. Following excision, incisions were
      made into the tumor with the two devices. Thermal injury depth, margin distance,
      tissue type, and histological effect were compared on the same breast tissue cut
      with each excision instrument. A probability evaluation of close and positive
      margin cases for the true tumor margins was conducted. RESULTS: Compared to
      traditional electrosurgery, the low-thermal-injury instrument reduced collagen
      denaturation depth from 435 to 102 um (77%), fused tissue depth from 262 to 87 um
      (67%), and distortion depth from 1,132 to 774 um (30%). CONCLUSIONS: Based on
      analysis of the close subset of the true margins, using the traditional
      electrosurgical device in place of the low-thermal-injury device would have
      resulted in 48% of the close margin samples being negatively converted to false
      positive, and in 11% converting from close to false-negative. The methodology of
      this work may be readily applied to larger, more definitive studies.

PMID- 21744350
TI  - De novo intra-pancreatic cholangiocarcinoma following liver transplantation for
      advanced primary sclerosing cholangitis.

PMID- 21744351
TI  - Lysophosphatidic acid (LPA) and endothelial differentiation gene (Edg) receptors
      in human pancreatic cancer.
AB  - Lysophosphatidic acid (LPA) is a naturally occurring phospholipid with diverse
      effects on various cells, ranging from immediate morphological change to long
      lasting cellular function alteration such as induction of stimulation of cell
      proliferation, survival, drug resistance, and motility. LPA interacts with cells
      through specific cell surface receptors. LPA1/Edg-2, LPA2/Edg-4, and LPA3/Edg-7
      are three most common LPA receptors. Herein we review the roles of LPA and its
      receptors in the carcinogenesis of human malignancies, with focus on pancreatic
      cancer.

PMID- 21744352
TI  - Elevated expression of Rad51 is correlated with decreased survival in resectable
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Rad51 plays a critical role in homologous recombination and
      correlates with many human malignancies. However, its role and clinical
      significance in esophageal squamous cell carcinoma (ESCC) has not been clarified.
      The purpose of this study was to explore the clinicopathological correlation and
      prognostic significance of Rad51 expression in a group of ESCC patients. METHODS:
      We evaluated Rad51 expression in 230 surgically resected ESCC specimens by
      immunochemistry using tissue microarray and correlated with clinicopathological
      features including post-operation survival. RESULTS: There was no significant
      correlation between Rad51 expression and clinicopathological characteristics in
      terms of age, sex, tumor location, histologic grade, T, N categories, and TNM
      stage. The Kaplan-Meier survival analysis showed that high expression of Rad51
      indicated a poorer disease free survival (DFS) of ESCC patients compared with the
      patients with low expression of Rad51 (P = 0.031), similar result also shown in
      overall survival (OS) analysis (P = 0.034). Furthermore, Rad51 expression could
      stratify node positive patients in DFS (P = 0.021) and OS (P = 0.035).
      Multivariate analysis confirmed the Rad51 expression was an independent
      prognostic factor for DFS (HR = 1.603, P = 0.013) and OS (HR = 1.555, P = 0.021)
      of ESCC patients. CONCLUSIONS: Elevated expression of Rad51 is associated with
      poor prognosis for resectable ESCC patients.

PMID- 21744353
TI  - Prognostic impact of microscopic positive margin in gastric cancer patients.
AB  - BACKGROUND: Complete resection with negative surgical margins has been a long
      held surgical philosophy based on the concept that even minimal remaining cancer
      cells will develop recurrences. OBJECTIVES: This study investigated the clinical
      significance of microscopic positive margin on the outcome of patients with
      gastric cancers. METHODS: The relationships between the margin status and other
      clinicopathologic factors were examined in gastric cancer patients undergoing
      gastrectomy, and then the prognostic impact of the margin status was evaluated by
      univariate and multivariate analysis. RESULTS: The microscopic positive margin
      was identified in 23 patients (2.8%) by standard H&E staining. The positive
      margin showed a strong correlation significantly with tumor size (P < 0.05).
      Microscopic positive margin was found to be a significant prognostic factor on
      univariate analysis (5-year survival rate 51.9% vs. 82.2%, P < 0.0001), as well
      as multivariate analysis (risk ratio 3.24, 95% CI: 1.24-6.50, P < 0.01). Detailed
      analysis of margin status demonstrated that patients with positive margin in a
      deep site and/or in multiple layers showed poor survival. CONCLUSIONS:
      Microscopic positive margin was found to be an independent prognostic factor in
      gastric cancer patients. The status of the surgical margin might provide useful
      information for selecting additional treatments and performing intensive follow
      up.

PMID- 21744354
TI  - Evaluating the toxic and beneficial effects of jering beans (Archidendron
      jiringa) in normal and diabetic rats.
AB  - BACKGROUND: Jering (Archidendron jiringa) is eaten in the tropics and
      traditionally extolled for treating diabetes, high blood pressure and eliminating
      bladder stones. Jering contains an unusual amino acid-djenkolic acid (S,S'
      methylenebiscysteine)-which may form sharp crystals in the urinary tract, causing
      pain and haematuria. This study evaluates the beneficial and toxic effects of
      dietary jering on tissues and organs in normal and diabetic rats. RESULTS:
      Dietary jering administered orally to diabetic rats significantly reduced the
      blood glucose in the streptozotocin-induced diabetic rats to normal levels after
      about 12 weeks. Jering improved the rats' appetite, body weight, organ oxidative
      status and number of active islets of Langerhans in both diabetic and normal
      rats, after 15 weeks of treatment. Although dietary jering showed beneficial
      effects to diabetic eye lens, lung and pancreas, it caused hypertrophy and
      lesions to the heart, kidney, liver, lung and pancreas of normal rats.
      CONCLUSION: Chronic jering consumption showed toxic effects to the heart, kidney,
      liver and pancreas of normal rats but produced some beneficial effects to
      diabetic rats.

PMID- 21744355
TI  - Arsenic contamination in sesame and possible mitigation through organic
      interventions in the lower Gangetic Plain of West Bengal, India.
AB  - BACKGROUND: The widespread geogenic arsenic contamination of groundwater in the
      Gangetic Delta of West Bengal, leading to toxicities through the food chain
      principally through irrigated rice-drew due attention from researchers. Oilseeds
      such as sesame might be a remunerative alternative to rice and can be grown with
      small quantities of contaminated groundwater. RESULTS: The present study was
      conducted to explore the efficiency of organic matter in reducing arsenic
      accumulation in sesame. Accumulation of total arsenic in sesame seed and
      available arsenic in post-harvest soils varied from 0.08 to 0.58 mg kg(-1) and
      from 3.87 to 8.89 kg ha(-1) , respectively. The organic manures added as soil
      amendment significantly reduced the accumulation (concentration) of arsenic in
      sesame seed to a maximum extent of 65.5% (vermicompost), 50% (phosphocompost),
      42% (mustard cake) and 40% (farmyard manure (FYM)) compared with the control
      counterpart. The risk associated with dietary exposure to arsenic-contaminated
      sesame oil reached a value of 15.55% of provisional tolerable weekly intake for
      arsenic at the maximum accumulation of arsenic in sesame oil. CONCLUSION:
      Substantial accumulation of arsenic in the soil-plant system was found. Risks of
      exposure to arsenic-contaminated oil remained considerably high. Irrigation
      through surface water and organic amendments both significantly reduced arsenic
      accumulation in sesame.

PMID- 21744356
TI  - Continuous hydrolysis of modified wheat gluten in an enzymatic membrane reactor.
AB  - BACKGROUND: The low solubility of wheat gluten is one of the major limitations to
      its use in food processing, and enzymatic hydrolysis has been found to be an
      effective way to prepare more soluble bioactive peptides from gluten. The aim of
      this study was to prepare bioactive peptides from modified wheat gluten (MWG) in
      a continuous enzymatic membrane reactor (EMR) that allowed rapid separation of
      low-molecular-weight peptides from hydrolysates, thus avoiding the disadvantages
      of batch reaction such as inefficient use of enzymes, inconsistent products due
      to batch-to-batch variation, substrate-product inhibition, low productivity and
      excessive hydrolysis. RESULTS: Wheat gluten was modified to decrease its lipid
      and starch contents in order to prevent membrane fouling. The optimal working
      conditions for Alcalase to hydrolyse MWG in the EMR were a substrate
      concentration of 20 g L(-1) , an enzyme/substrate ratio of 0.03, an operating
      pressure of 0.04 MPa, a temperature of 40  degrees C and a pH of 9. The operating
      stability of the EMR (including residual enzyme activity, productivity and
      capacity) was high. The permeate fractions showed antioxidant activities that
      were mostly due to low-molecular-weight peptides. A simple theoretical kinetic
      model was successfully applied to the enzymatic hydrolysis of MWG in the EMR.
      CONCLUSION: Modification of wheat gluten made the continuous enzymatic membrane
      reaction more efficient and the EMR proved to be an effective means of producing
      peptides with particular properties and bioactivities. The permeate fractions
      (mainly < 1000 Da) were homogeneous and stable and also showed strong antioxidant
      activities.

PMID- 21744357
TI  - Simultaneous separation and purification of flavonoids and oleuropein from Olea
      europaea L. (olive) leaves using macroporous resin.
AB  - BACKGROUND: This study developed a feasible process to simultaneously separate
      and purify polyphenols, including flavonoids and oleuropein, from the leaves of
      Olea europaea L. Macroporous resins were used as the separation and purification
      materials. The performance and separation capabilities of eight resins (D101,
      DM130, HPD450, LSA-21, LSA-40, 07C, LSD001 and HPD600) were systematically
      evaluated. The contents of target polyphenols in different extracts were
      determined using ultraviolet (for flavonoids) and high-performance liquid
      chromatographic (for oleuropein) methods. The static adsorption and desorption
      results showed that resin LSA-21 had better adsorption properties among the eight
      resins. Influential factors such as extraction method, pH value of feeding
      solution, desorption solution, adsorption kinetics and adsorption isotherm, etc.
      to the extraction and purification of these polyphenols were successively
      investigated on resin LSA-21. RESULTS: The target flavonoids and oleuropein were
      selectively purified using resin LSA-21. Compared with the contents in raw
      leaves, the contents of total flavonoids and oleuropein in the final purified
      products were increased 13.2-fold (from 16 to 211 g kg(-1) ) and 7.5-fold (from
      120 to 902 g kg(-1) ) with recovery yields of 87.9% and 85.6%, respectively.
      CONCLUSION: This extraction and purification method could be used in the large
      scale enrichment or purification of flavonoids, oleuropein and other polyphenols
      from O. europaea L. leaves or other herbal materials in industrial, food
      processing and medical manufacture.

PMID- 21744358
TI  - Supercritical CO2extraction of oleoresin from marigold (Tagetes erecta L.)
      flowers and determination of its antioxidant components with online HPLC-ABTS(.+)
      assay.
AB  - BACKGROUND: Marigold is a traditional medicine herb which shows good
      pharmacological activity in many aspects. It is very important to obtain and
      investigate the specific bioactive compounds from marigold. The objective of the
      study was to extract the oleoresin from marigold with supercritical CO(2) (SC
      CO(2) ) at different pressures and temperatures, detect the fatty acid
      composition by gas chromatography-mass spectrometry and investigate the
      antioxidative components in the extracts by combined online high-performance
      liquid chromatography-2,2-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid (HPLC
      ABTS(*+) ) post-column assay and HPLC-tandem mass spectrometry. RESULTS: For the
      pressure range (20-40 MPa) and temperature range (30-70  degrees C), 30 MPa/70 
      degrees C gave the highest yield of oleoresin (58.9 g kg(-1) ). The dominant
      fatty acids of marigold flower oleoresin were linoleic acid (>26.41%), palmitic
      acid (>24.22%) and oleinic acid (>20.12%). Significant effects of the extraction
      pressure and temperature on the antioxidant activity were observed (P < 0.05).
      Lutein esters, alpha-tocopherol, beta-tocopherol, gamma-tocopherol and delta
      tocopherol were the dominant antioxidant compounds in the extracts. CONCLUSION:
      The study has shown that the yield and total antioxidant activity of the marigold
      extracts were affected by the pressure and temperature of SC-CO(2) , and that
      online HPLC technique could be used as an efficient and rapid method for
      separation and identification of bioactive compounds from a complex mixture.

PMID- 21744359
TI  - Effect of breed on performance and meat quality of first parity sows in a
      seasonal organic rearing system.
AB  - BACKGROUND: The objective was to compare the performance and meat quality of two
      different pig breeds: the modern crossbred Landrace * Yorkshire (LY) and the
      traditional Danish Black-Spotted (BS) breed. The LY gilts and four of the BS
      gilts were inseminated with semen from Duroc (D) boars; the remaining BS gilts
      were served by BS boars. The experiment was performed on 26 gilts over 2 years.
      RESULTS: The BS breed in general had smaller litter sizes and weaned on average
      in terms of kg piglet 35% less than the modern breed combination. Crossbred
      piglets of BS * D had growth rates from birth to weaning comparable with piglets
      of LY * D. BS first parity sows were significantly fatter and less meaty, and the
      meat was significantly redder and darker compared to LY. The sensory profiling
      revealed increased sweetness, crumbliness and tenderness in BS. Further, the fat
      of the BS breed seemed to be characterized by a special nutty taste. CONCLUSION:
      The traditional breed has lower productivity and thereby higher costs of
      production compared to the modern genotypes. On the other hand, the meat and fat
      of the traditional purebred have special characteristics that might trigger a
      market premium.

PMID- 21744360
TI  - Benefits of beta-xylanase for wheat biomass conversion to bioethanol.
AB  - BACKGROUND: The efficiency of bioethanol production from wheat biomass is related
      to the quality of end products as well as to safety criteria of co-products such
      as distiller's dried grains with solubles (DDGS). The inclusion of a new
      biocatalyst for non-starch polysaccharide degradation in fermentation processes
      could be one of the solutions. The objective of this study was to evaluate the
      influence of beta-xylanases in combination with traditional amylolytic enzymes on
      the efficiency of bioethanol production and DON detoxification during
      fermentation of Fusarium-contaminated wheat biomass with high concentration of
      deoxynivalenol (DON; 3.95 mg kg(-1)). RESULTS: The results showed that the
      negative effect of Fusarium spp. on yield and quality of bioethanol could be
      eliminated by the application of Trichoderma reesei xylanase in combination with
      amylolytic enzymes. This technological solution allowed to increase the
      concentration of ethanol in the fermented wort by 35.3% and to improve the
      quality of bioethanol by decreasing the concentrations of methanol, methyl
      acetate, isoamyl and isobutyl alcohols. Mass balance calculations showed that
      DDGS was the main source of DON contamination, comprising 74% of toxin found in
      wheat biomass. By using new enzyme combination for wheat biomass
      saccharification, a higher level of detoxification (41%) of DON was achieved
      during the fermentation process. CONCLUSION: The addition of Trichoderma reesei
      xylanase played a positive role in bioethanol production from Fusarium
      contaminated wheat biomass, indicating that the yeast-growing medium was enriched
      during the enzymatic treatment.

PMID- 21744361
TI  - The use of high-performance liquid chromatography to detect ochratoxin A in dried
      figs from the Spanish market.
AB  - BACKGROUND: Detection and quantification of ochratoxin A (OTA) in dried fig
      samples purchased in Spain has been carried out using high-performance liquid
      chromatography with fluorescence detection after extraction with methanol and
      sodium bicarbonate, and clean-up by using an immunoaffinity column. RESULTS: The
      detection limit of the method was 0.06 ng g(-1), and the limit of quantification
      0.18 ng g(-1) . OTA was detected in 31 (88.6%) out of 35 samples of dried figs
      analysed, with concentrations that ranged from < 0.1 to 277 ng g(-1). However,
      only three samples contained OTA concentrations above the tolerable level set by
      European Commission regulations for dried vine fruits (10 ng g(-1)). CONCLUSION:
      The results of this survey show the value of monitoring OTA in dried figs
      especially if they are home grown.

PMID- 21744362
TI  - Development of algorithms for detecting citrus canker based on hyperspectral
      reflectance imaging.
AB  - BACKGROUND: Automated discrimination of fruits with canker from other fruit with
      normal surface and different type of peel defects has become a helpful task to
      enhance the competitiveness and profitability of the citrus industry. Over the
      last several years, hyperspectral imaging technology has received increasing
      attention in the agricultural products inspection field. This paper studied the
      feasibility of classification of citrus canker from other peel conditions
      including normal surface and nine peel defects by hyperspectal imaging. RESULTS:
      A combination algorithm based on principal component analysis and the two-band
      ratio (Q(687/630)) method was proposed. Since fewer wavelengths were desired in
      order to develop a rapid multispectral imaging system, the canker classification
      performance of the two-band ratio (Q(687/630)) method alone was also evaluated.
      The proposed combination approach and two-band ratio method alone resulted in
      overall classification accuracy for training set samples and test set samples of
      99.5%, 84.5% and 98.2%, 82.9%, respectively. CONCLUSION: The proposed combination
      approach was more efficient for classifying canker against various conditions
      under reflectance hyperspectral imagery. However, the two-band ratio (Q(687/630))
      method alone also demonstrated effectiveness in discriminating citrus canker from
      normal fruit and other peel diseases except for copper burn and anthracnose.

PMID- 21744363
TI  - Prenatal features of Noonan syndrome: prevalence and prognostic value.
AB  - OBJECTIVE: Noonan syndrome (NS) is a common autosomal dominant developmental
      disorder, mainly characterized by congenital heart defects, short stature, and a
      variable degree of developmental delay. We have reviewed the prenatal findings in
      NS and we have correlated them with genotype and postnatal phenotype. METHODS:
      The cohort consisted of 47 patients with molecular diagnosis of NS. Prenatal and
      postnatal phenotypes were assessed by analysis of medical records, and clinical
      follow-up. Postnatal clinical phenotype, congenital heart disease,
      neuropsychomotor development, and growth pattern were arbitrarily scored in terms
      of severity. RESULTS: Mean age at diagnosis of NS was 7 years (ranging from birth
      to 38 years). Abnormal maternal serum triple screen was present in 36% of cases,
      nuchal translucency > 2.5 mm in 41%, polyhydramnios in 38% and fetal anomalies at
      prenatal ultrasonography in 21%. No statistical association was observed between
      prenatal findings and NS genotype or scores of postnatal clinical phenotype,
      congenital heart disease, neuropsychomotor development, or short stature.
      Presence of morphologic fetal anomalies at ultrasonography was associated with
      developmental delay/intellectual disabilities (p < 0.001) and juvenile
      myelomonocytic leukaemia (p = 0.006). CONCLUSIONS: Abnormal prenatal findings are
      frequent in NS pregnancies, though they are not specific and most are not useful
      for the prediction of the postnatal phenotype.

PMID- 21744364
TI  - Twin-twin transfusion syndrome treated with laser surgery: postnatal prevalence
      of congenital heart disease in surviving recipients and donors.
AB  - OBJECTIVE: To assess postnatal prevalence of congenital heart disease (CHD) in
      surviving twins treated for twin-twin transfusion syndrome (TTTS) with laser
      surgery. METHODS: Patients who underwent laser surgery for TTTS at a single
      institution were prospectively enrolled between January 2009 and May 2010.
      Preoperative fetal echocardiography was performed. Perinatal outcomes were
      obtained via postnatal echocardiograms and review of medical records. CHD was
      defined as unequivocal structural cardiac pathology; patent foramen ovale and
      patent ductus arteriosus were excluded. RESULTS: Fifty pregnancies with TTTS were
      enrolled, with the following Quintero stage distribution: stage I, 10%; stage II,
      22%; stage III, 50%; and stage IV, 18%. Of the 88 fetuses born alive, 84 patients
      (95.5%) completed postnatal cardiac evaluation. Overall postnatal prevalence of
      CHD was 15.5% (13 of 84): 15.6% of recipient twins and 15.4% of donor twins.
      Three patients required cardiac intervention during infancy. Among liveborn twins
      with CHD, the overall prenatal detection rate was 30.8% (4/13), comprising 16.7%
      (1/6) of donors compared with 42.9% (3/7) of recipients. CONCLUSION: Following
      successful laser surgery for TTTS, an increased and comparable postnatal
      prevalence of CHD occurs among both former recipients and donors.

PMID- 21744365
TI  - Monochorionic twins discordant for congenital heart disease: a referral center's
      experience and possible pathophysiologic mechanisms.
AB  - OBJECTIVE: To describe the spectrum of cardiac defects in monochorionic (MC)
      twins discordant for congenital heart disease (CHD) in a referral center
      population. METHOD: Retrospective study of all twin gestations undergoing
      echocardiography between 2000 and 2009 at our institution. RESULTS: A total of
      356 twin pairs were evaluated during the study period, 202 for suspected twin
      twin transfusion syndrome (TTTS) and the remainder for other indications. Twenty
      nine MC pairs were discordant for CHD: laterality defects, 24% [right (2) or left
      (3) isomerism (3), primitive heart (2)]; ventricular hypoplasia secondary to
      semilunar valve obstruction, 14% [hypoplastic left heart syndrome (2), severe
      pulmonary stenosis (PS) or atresia (2)]; valvar dysplasias in TTTS recipients,
      27% [PS (4), mitral/tricuspid dysplasia (4)]; conjoining, 14% (4); and other
      developmental errors, 21% [conotruncal (1), tricuspid atresia (2), ventricular
      septal defect (2)]. CONCLUSIONS: The spectrum of lesions in individuals assumed
      to be genetically identical and the disproportionate incidence of laterality and
      ventricular hypoplasia in this population leads us to propose potential
      mechanisms for the development of CHD in this population including local
      environmental or epigenetic factors influencing gene expression differentially,
      abnormal reciprocal laterality signaling between twinned embryos, or placental
      vascular factors affecting hemodynamics, either early in gestation or later in
      the setting of TTTS, leading to valvar lesions and ventricular hypoplasia.

PMID- 21744366
TI  - Congenital microgastria: a rare cause of failure to visualise the fetal stomach.

PMID- 21744367
TI  - First-trimester prediction of preeclampsia using metabolomic biomarkers: a
      discovery phase study.
AB  - OBJECTIVE: We tested the hypothesis that first-trimester metabolic biomarkers
      offered a unique profile in women with preeclampsia (PE) in the second half of
      pregnancy, compared with controls. METHOD: We conducted a nested case-control
      study within a prospective cohort of pregnant women followed from the first
      trimester to delivery. Cases were those who developed PE at any gestational age,
      and these were compared with a control group without adverse pregnancy outcome,
      matched for gestational age within 3 days. We analyzed maternal blood obtained at
      11-14 weeks' gestation for 40 acylcarnitine species (C2-C18 saturated,
      unsaturated, and hydroxylated) and 32 amino acids by liquid chromatography tandem
      mass spectrometry. Logistic regression modeling estimated the association of each
      metabolite with development of PE. RESULTS: We compared 41 cases with PE with 41
      controls and found four metabolites (hydroxyhexanoylcarnitine, alanine,
      phenylalanine, and glutamate) that were significantly higher in the cases with
      PE. The area under the curve (AUC) using these metabolites individually to
      predict PE varied from 0.77 to 0.80, and when combined, the AUC improved to 0.82
      [95% confidence interval (95% CI): 0.80-0.85] for all cases of PE and 0.85 (95%
      CI: 0.76-0.91) for early onset PE. CONCLUSION: Our findings suggest a potential
      role for first-trimester metabolomics in screening for PE.

PMID- 21744368
TI  - Second trimester biparietal diameter size and the risk of adverse pregnancy
      outcomes.
AB  - OBJECTIVE: To identify the relationship between biparietal diameter (BPD) in the
      second trimester and adverse pregnancy outcomes in low-risk pregnancies. METHOD:
      This prospective cohort study was performed on 2219 singleton pregnant women from
      August 2008 to March 2010. The gestational age-specific percentiles of BPD at 17
      to 24 weeks of gestation were established to categorize participants into three
      groups: a BPD < 10th percentile as small BPD, between 10th and 90th percentile as
      normal BPD and > 90th percentile as large BPD. Using logistic regression
      analysis, the association between BPD < 10th and > 90th percentile with pregnancy
      outcomes was evaluated after controlling for confounding factors. RESULTS: There
      was a significantly increased risk of macrosomia [odds ratio (OR(adj)) = 2.1; 95%
      confidence intervals (CI), 1.23-3.78] and preterm labor (PTL) (OR(adj) = 1.9; 95%
      CI, 1.19-3.05) in fetuses with a BPD > 90th percentile compared with fetuses with
      a normal BPD, and there was a significant relationship between small for
      gestational age (SGA) at delivery and a BPD < 10th percentile at the second
      trimester (OR(adj) = 2.4; 95% CI, 1.77-3.52). No association was present between
      preeclampsia and second trimester BPD. CONCLUSION: BPD in the first half of
      pregnancy is related to fetal size at term and risk of PTL.

PMID- 21744369
TI  - Diagnosis of fetal urinary tract malformations: prenatal management and postnatal
      outcome.
AB  - OBJECTIVE: To evaluate prenatal management and to define the criteria of gravity
      for accurate assessment of the renal and overall prognosis of fetuses presenting
      malformations of the urinary tract. METHODS: We carried out a retrospective study
      of 127 cases of urinary tract malformation. We carried out descriptive
      statistical and univariate analyses as a function of severity criteria and the
      outcome of pregnancy. RESULTS: One-third of fetuses presented associated
      extrarenal malformations and 10% of the karyotypes were abnormal. There were more
      abortions in case of decrease in amniotic fluid volume (p < 0.001), extent of
      renal damage (p < 0.05), presence of associated extrarenal malformations (p <
      0.05), early diagnosis of the malformation (p < 0.001) and presence of
      chromosomal syndrome (p = 0.01). In our study, there was an excellent correlation
      between prenatal data and pathological findings for the fetus following abortions
      for medical reasons or obtained during the surveillance of live-born children.
      Fetal biochemistry made very little contribution. CONCLUSION: In cases of urinary
      tract malformation, this work confirms the need for regular and frequent
      ultrasound scans, checking for the echographic factors indicative of gravity and
      for adapted karyotyping. It also demonstrates that pluridisciplinary management
      is necessary for the prenatal evaluation of renal and overall fetal prognosis.

PMID- 21744370
TI  - Corrections by melatonin of liver mitochondrial disorders under diabetes and
      acute intoxication in rats.
AB  - The aim of the present work was to investigate the mechanisms of oxidative damage
      of the liver mitochondria under diabetes and intoxication in rats as well as to
      evaluate the possibility of corrections of mitochondrial disorders by
      pharmacological doses of melatonin. The experimental (30 days) streptozotocin
      induced diabetes mellitus caused a significant damage of the respiratory activity
      in rat liver mitochondria. In the case of succinate as a respiratory substrate,
      the ADP-stimulated respiration rate V3 considerably decreased (by 25%, p < 0.05)
      as well as the acceptor control ratio (ACR) V3/V2 markedly diminished (by 25%, p
      < 0.01). We observed a decrease of the ADP-stimulated respiration rate V3 by 35%
      (p < 0.05), with glutamate as substrate. In this case, ACR also decreased (by
      20%, p < 0.05). Surprisingly, the phosphorylation coefficient ADP/O did not
      change under diabetic liver damage. Acute rat carbon tetrachloride-induced
      intoxication resulted in considerable decrease of the phosphorylation coefficient
      because of uncoupling of the oxidation and phosphorylation processes in the liver
      mitochondria. The melatonin administration during diabetes (10 mg.kg-1 body
      weight, 30 days, daily) showed a considerable protective effect on the liver
      mitochondrial function, reversing the decreased respiration rate V3 and the
      diminished ACR to the control values both for succinate-dependent respiration and
      for glutamate-dependent respiration. The melatonin administration to intoxicated
      animals (10 mg.kg-1 body weight, three times) partially increased the rate of
      succinate-dependent respiration coupled with phosphorylation. The impairment of
      mitochondrial respiratory plays a key role in the development of liver injury
      under diabetes and intoxication. Melatonin might be considered as an effector
      that regulates the mitochondrial function under diabetes.

PMID- 21744371
TI  - Women's experience of termination of pregnancy for fetal anomaly: effects of
      socio-political evolutions in France.
AB  - OBJECTIVE: To analyse the experiences of women facing a termination of pregnancy
      for fetal anomaly (TOPFA) in relation to decisional aspects, attitudes towards
      the fetus' body and the effects of postpartum depression. The method is based on
      a two-stage questionnaire given to 120 women who underwent a TOPFA between 2005
      and 2006 in a Parisian Prenatal Diagnosis Department and compared to a similar
      study carried out in 1999 in the same department. RESULTS: In 2005, 68/120 women
      (57%) compared to 32/103 (32%) in 99 (p < 0.001) believed that the decision of
      pregnancy termination belongs to couples and doctors together. However, in
      advanced pregnancy or fetal pathology related to mental deficiency, a higher
      proportion of women believe that the decision should belong to the parents alone.
      In 2005, 66% of the women (78/118) compared to (42/103) 41% in 1999 (p < 0.001),
      chose to see their fetus after the termination. Postpartum depression score was
      positive in one third of the 2005 series and higher in younger women. CONCLUSION:
      Our study suggests that women differentiate between various decision-making
      actors depending on the type of pregnancy termination. The differences observed
      between 1999 and 2005 suggest a strong interaction between women's experiences,
      legislation and practices.

PMID- 21744372
TI  - Into the deep: new discoveries at the base of the green plant phylogeny.
AB  - Recent data have provided evidence for an unrecognised ancient lineage of green
      plants that persists in marine deep-water environments. The green plants are a
      major group of photosynthetic eukaryotes that have played a prominent role in the
      global ecosystem for millions of years. A schism early in their evolution gave
      rise to two major lineages, one of which diversified in the world's oceans and
      gave rise to a large diversity of marine and freshwater green algae (Chlorophyta)
      while the other gave rise to a diverse array of freshwater green algae and the
      land plants (Streptophyta). It is generally believed that the earliest-diverging
      Chlorophyta were motile planktonic unicellular organisms, but the discovery of an
      ancient group of deep-water seaweeds has challenged our understanding of the
      basal branches of the green plant phylogeny. In this review, we discuss current
      insights into the origin and diversification of the green plant lineage.

PMID- 21744373
TI  - BAFF-R gene induced by IFN-gamma in multiple myeloma cells is related to NF
      kappaB signals.
AB  - B-cell activating factor (BAFF) is a potent cell-survival factor expressed in
      many haematopoietic cells. BAFF regulates B-cell survival, differentiation and
      proliferation by binding to three tumour necrosis factor receptors: transmembrane
      activator, calcium modulator and cyclophilin ligand interactor; B-cell maturation
      antigen; and BAFF receptor (BAFF-R). Although BAFF-R is produced by interferon
      gamma (IFN-gamma), the underlying mechanism remains elusive. In this study, we
      examined the effects of IFN-gamma on BAFF-R expression in cultured human multiple
      myeloma cells (KM3) both at the transcriptional and posttranscriptional levels.
      Incubation of KM3 cells with IFN-gamma elevated the expression of BAFF-R mRNA and
      protein levels. IFN-gamma elicited marked enhancement of the human BAFF-R
      promoter activity and nuclear factor kappa B (NF-kappaB) DNA binding activity. NF
      kappaB dependent on the human BAFF-R gene might be regulated via a
      transcriptional event through one putative NF-kappaB site on the BAFF-R gene
      promoter. These results provide a molecular mechanism for the increase in
      expression of the BAFF-R gene that is induced by proinflammatory cytokines in
      responsive cells.

PMID- 21744374
TI  - Empowering plant evo-devo: virus induced gene silencing validates new and
      emerging model systems.
AB  - It is increasingly recognized that current established model systems are not
      sufficient to understand the evolution of biodiversity. The main limitation in
      developing additional model systems is the difficulty or inability to perform
      functional studies of target genes. Evolutionary developmental (evo-devo)
      biologists have adopted a transient transgenic technique, developed over the last
      decade for agricultural applications, which is allowing functional studies in the
      most disparate plant lineages. From monocots to dicots and from herbs to trees,
      virus-induced gene silencing (VIGS) has opened up a world of opportunities in
      plant evo-devo.

PMID- 21744375
TI  - Psychometric evaluation of the eating disorder examination and eating disorder
      examination-questionnaire: a systematic review of the literature.
AB  - OBJECTIVE: The purpose of this study was to systematically review the reliability
      of scores on the Eating Disorder Examination (EDE) and the Eating Disorder
      Examination-Questionnaire (EDE-Q) and to examine the validity of their use as
      measures of eating disorder symptoms. METHOD: Articles describing the
      psychometric properties of the EDE and EDE-Q were identified in a systematic
      search of major computer databases and a review of reference lists. Articles were
      selected based on a priori inclusion and exclusion criteria. RESULTS: Fifteen
      studies were identified that examined the psychometrics of the EDE, whereas 10
      studies were found that examined the psychometrics of the EDE-Q. DISCUSSION: Both
      instruments demonstrated reliability of scores. There is evidence that scores on
      the EDE and EDE-Q correlate with scores on measures of similar constructs and
      support for using the instruments to distinguish between cases and non-cases.
      Additional research is needed to broaden the generalizability of the findings.

PMID- 21744376
TI  - Concerns related to eating, weight, and shape: typologies and transitions in men
      during the college years.
AB  - OBJECTIVE: How to best classify concerns related to eating, weight, and shape
      (CREWS) in men remains an open question. Research on men considering CREWS during
      different developmental periods could be particularly informative. METHOD:
      Focusing on one potentially dynamic developmental period, this study charts the
      course of CREWS in men over the college years. Latent class/latent transition
      analysis identified typologies of weight- and shape-influenced self judgment,
      limiting attempts, fasting, overeating, binge eating, self-induced vomiting, and
      laxative or diuretic abuse for 1,025 men over the four traditional college years.
      RESULTS: Three classes emerged: (1) no obvious pathological eating-related
      concerns (61-65%); (2) a high likelihood of limiting attempts and a moderately
      high likelihood of overeating (31-34%); (3) pervasive bulimic-like concerns (4
      6%). Class membership was highly stable across assessment occasions. DISCUSSION:
      The results contribute to the growing literature on empirically derived
      classifications of CREWS and indicate that for many men CREWS are a chronic
      presence during the college years.

PMID- 21744377
TI  - Duloxetine in the treatment of binge eating disorder with depressive disorders: a
      placebo-controlled trial.
AB  - OBJECTIVE: This study evaluated duloxetine in the treatment of binge eating
      disorder (BED) with comorbid current depressive disorders. METHOD: In this 12
      week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and
      Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current
      depressive disorder received duloxetine (N = 20) or placebo (N = 20). The primary
      outcome measure was weekly binge eating day frequency. RESULTS: In the primary
      analysis, duloxetine (mean 78.7 mg/day) was superior to placebo in reducing
      weekly frequency of binge eating days (p = .04), binge eating episodes (p = .02),
      weight (p = .04), and Clinical Global Impression-Severity of Illness ratings for
      binge eating (p = .02) and depressive disorders (p = .01). Changes in body mass
      index and measures of eating pathology, depression, and anxiety did not differ
      between the two groups. DISCUSSION: Duloxetine may be effective for reducing
      binge eating, weight, and global severity of illness in BED with a comorbid
      current depressive disorder, but this finding needs confirmation in larger,
      placebo-controlled trials.

PMID- 21744378
TI  - Predicting nonsuicidal self-injury episodes over a discrete period of time in a
      sample of women diagnosed with bulimia nervosa: an analysis of self-reported
      trait and ecological momentary assessment based affective lability and previous
      suicide attempts.
AB  - OBJECTIVE: To examine the moderating effect of trait affective lability on the
      relationship between past suicidal behavior and future nonsuicidal self-injury
      (NSSI). METHOD: A total of 127 adult females diagnosed with bulimia nervosa took
      part in this study. We hypothesized that individuals with greater levels of self
      reported trait affective lability and a greater number of past suicide attempts
      would engage in a greater number of NSSI episodes over the course of 2 weeks than
      would individuals lacking elevations in one or both of those variables,
      controlling for average level of negative affect and affective lability as
      measured through ecological momentary assessment (EMA). RESULTS: The two-way
      interaction of trait affective lability and past suicidal behavior predicted
      participants' number of NSSI episodes during the course of the study. DISCUSSION:
      Interaction of self-reported trait affective lability and past suicidal behavior
      may exhibit clinical utility in the prediction of patients' imminent risk of
      engaging in NSSI.

PMID- 21744379
TI  - Neuroimage evidence and the insanity defense.
AB  - The introduction of neuroscientific evidence in criminal trials has given rise to
      fears that neuroimagery presented by an expert witness might inordinately
      influence jurors' evaluations of the defendant. In this experiment, a diverse
      sample of 1,170 community members from throughout the U.S. evaluated a written
      mock trial in which psychological, neuropsychological, neuroscientific, and
      neuroimage-based expert evidence was presented in support of a not guilty by
      reason of insanity (NGRI) defense. No evidence of an independent influence of
      neuroimagery was found. Overall, neuroscience-based evidence was found to be more
      persuasive than psychological and anecdotal family history evidence. These
      effects were consistent across different insanity standards. Despite the non
      influence of neuroimagery, however, jurors who were not provided with a
      neuroimage indicated that they believed neuroimagery would have been the most
      helpful kind of evidence in their evaluations of the defendant.

PMID- 21744380
TI  - Phylogenetic distribution of fungal mycosporines within the Pucciniomycotina
      (Basidiomycota).
AB  - The synthesis of the UV Absorbing compounds named mycosporines (MYCs) has been
      detected in a few basidiomycetous yeast groups. Conspicuous accumulation of
      mycosporine-glutaminol-glucoside (MGG) in yeasts requires photo-induction and its
      photoprotective function has been postulated. The distribution of the ability to
      produce MYCs appeared to be related to the yeast taxonomic affiliation. In view
      of the potential significance of MYCs in yeast taxonomy, we here studied the
      distribution of this trait among dimorphic basidiomycetes of the
      Pucciniomycotina. Of the 94 fungal species (377 strains and 33 genera) tested,
      almost half were MYC-positive and MGG was the main compound produced. MGG
      synthesis was observed for representatives of five of seven Pucciniomycotina
      classes, indicating that this trait is widely distributed in this group. MGG
      detection proved useful for the differentiation of species of the polyphyletic
      genera, such as Rhodotorula and Sporobolomyces, that are phylogenetically
      separated. MGG quantification and UV tolerance studies in Cystobasidiomycetes
      supported the idea that the habitat of origin of each strains is important in the
      level of MGG synthesis and that MYCs have a photoprotective function in yeasts.
      The taxonomic value of this trait in fungal systematics is discussed.

PMID- 21744381
TI  - Contextual and psychosocial influences on antiretroviral therapy adherence in
      rural Zimbabwe: towards a systematic framework for programme planners.
AB  - Great progress has been made in achieving universal access to antiretroviral
      therapy (ART). However, for successful viral suppression, patients must adhere to
      rigid and complex treatment regimens. With three quarters of antiretroviral (ARV)
      users in Africa adhering successfully, African countries have achieved
      extraordinary levels of adherence given the levels of poverty in which many ARV
      users live. Nevertheless, one quarter of ARV users still struggle to adhere and
      run the risk of experiencing viral replication, clinical progression or even drug
      resistance. Much has been written about ART adherence, but little has been done
      to systematically categorise the spectrum of factors that influence ART. In this
      paper, we use a Zimbabwean case study to develop a framework for ART programme
      planners and implementers seeking to identify and tackle social obstacles to
      adherence. We draw on interviews and group discussions with 25 nurses and 53
      adult ARV users, which we analysed through a three-tiered thematic approach,
      allowing us to categorise our findings into broader dimensions that can transcend
      our case study and be applied elsewhere. Our findings suggest that ART adherence
      is influenced by the material, symbolic, relational and institutional contexts in
      which ARV users live as well as the patient's motivation, participation and
      psychosocial responses to ART. This framework allows us to examine both the
      social context in which ART programmes are located and the psychosocial factors
      that influence patient behaviours. We offer this framework as a resource for ART
      programme planners and implementers seeking to improve ART compliance in resource
      poor settings.

PMID- 21744382
TI  - Lack of awareness of symptoms in people with dementia: the structural and
      functional basis.
AB  - OBJECTIVE: To review studies investigating the brain correlates of unawareness of
      cognitive and behavioural symptoms in people with dementia. DESIGN: A detailed
      search of the literature was conducted to include all the peer-reviewed studies
      published in English aimed at identifying the structural or functional brain
      correspondents of unawareness in dementia patients. Their results were
      interpreted in relation to the methodological differences in terms of type of
      dementia studied, the protocol adopted to measure lack of awareness, the imaging
      techniques employed, the experimental designs and statistical analyses performed.
      RESULTS: Eighteen studies undertaken to explore the functional and structural
      correlates of unawareness of cognitive symptoms in dementia were identified.
      Although their results showed a disparate range of brain correlates, they were
      mainly localized in frontal and temporo-parietal regions. CONCLUSIONS: Although
      the anatomical correlates of unawareness of disease in dementia have not yet been
      exhaustively explored, understanding the correlates of unawareness may also
      contribute to understand the brain correlates of self-awareness and self
      reflection. We discuss the current knowledge base and consider potential future
      directions for research.

PMID- 21744383
TI  - A randomized clinical trial of a writing workshop intervention to improve
      autobiographical memory and well-being in older adults.
AB  - BACKGROUND: Despite much research on methods to improve new learning and memory
      in old age, there is virtually no literature on the improvement of
      autobiographical memory (AM). The present study assessed the effectiveness of a
      structured autobiographical writing workshop for improving AM, mood and self
      concept in older adults. METHODS: Fifty-one nondemented older adults (67-96
      years) participated. AM was assessed with the Autobiographical Memory Interview
      (AMI) and the Remote Memory Word Association Task (RMWAT). After completing
      baseline (BL) testing, participants were randomized to a structured
      autobiographical writing workshop, a reminiscence group (active control
      condition) or a no-treatment control group. Follow-up testing was completed at 8
      and 34 weeks after BL. RESULTS: Repeated measures ANOVAs failed to reveal a group
      by-time interaction for any of the autobiographical memory (AM) measures. Across
      groups, there was a decrease in number of mid- and late-life events reported (on
      the AMI), and memories tended to be less detailed (on the RMWAT) although more
      pleasant memories were reported with repeated testing. Mood remained unchanged;
      ratings of self-concept improved across all groups. CONCLUSIONS: This is the
      first study of its kind to use a randomized group design to test an intervention
      for AM in older adults. In general, our specific intervention was ineffective for
      increasing recall from one's life story, mood or self-concept. Methodological
      limitations and suggestions for future investigation are discussed.

PMID- 21744384
TI  - Risk factors for postoperative cognitive and functional difficulties in abdominal
      aortic aneurysm patients: a three month follow-up.
AB  - BACKGROUND: Cognitive impairment and deficits in functional performance are major
      concerns following surgery, particularly for older patients. The objective of
      this study was to examine predictors of postoperative cognitive and functional
      difficulties and explore the relationship between presurgery and postsurgery
      cognitive ability and functional performance. METHODS: 89 patients undergoing
      elective abdominal aortic aneurysm (AAA) surgery were administered a battery of
      cognitive measures preoperatively, at the time of discharge from hospital and 3
      months postoperatively. Functional performance was evaluated by the Portland
      Adaptability Inventory (PAI), both pre and postsurgery. Symptoms of delirium were
      assessed during the first six postoperative days. RESULTS: A diagnosis of
      delirium had a mild effect on functional performance 3 months postoperatively.
      The strongest predictors of postoperative functional performance were the level
      of functioning presurgery, a longer length of hospital stay and the total number
      of days delirious. Cognitive impairment postsurgery was predicted by presurgery
      cognitive measures of verbal memory and psychomotor speed performance and the
      total number of days delirious. CONCLUSIONS: Functional performance outcomes for
      AAA patients 3 months postsurgery revealed no significant loss of functioning
      relative to presurgery levels, although longer length of hospital stay and
      greater number of days delirious was associated with somewhat poorer outcome on
      indicators of social and physical functioning. Cognitive impairment
      postoperatively was fairly mild but when it was found it was associated with
      number of days delirious and preoperative deficits in verbal memory and
      psychomotor speed.

PMID- 21744385
TI  - The economic impact of dementia in Europe in 2008-cost estimates from the
      Eurocode project.
AB  - OBJECTIVE: Care for demented people is very resource demanding, the prevalence is
      increasing and there is so far no cure. Cost of illness (CoI) studies are
      important by identifying the distribution of costs between different payers of
      care. The European Union (EU) funded the European Collaboration on Dementia
      (Eurocode) as part of the EU's 2005 work plan of the Community public health
      programme. Eurocode was administered by Alzheimer Europe. The aim was to describe
      the economic impact of dementia in Europe in 2008. METHODS: Eurocode's new
      estimates for dementia prevalence were included in a cost model based on
      published European CoI papers. For countries where no CoI figures were available,
      imputation was used. RESULTS: The total CoI of dementia in the EU27 in 2008 was
      estimated to be ?160 billion (?22 000 per demented per year), of which 56% were
      costs of informal care. The corresponding costs for the whole Europe was ?177
      billion. In northern Europe, the direct costs are estimated to be considerabe,
      while the cost of informal care is the major cost component in southern Europe.
      The sensitivity analysis showed a range for total EU27 costs between ?111 and 168
      billion. CONCLUSIONS: The estimated CoI in this study is higher than in previous
      studies. There are also large differences in different European regions.
      Notwithstanding the methodological challenges, the societal costs of dementia in
      Europe are very high which in turn have substantial resource impacts on the
      social and health care systems in Europe.

PMID- 21744386
TI  - Development and validation of an instrument to detect depression in nursing
      homes. Nursing homes short depression inventory (NH-SDI).
AB  - Depression is often overlooked in elderly nursing home residents because symptoms
      may be masked or dismissed as an inevitable consequence of ageing. Current tools
      for the detection of depression in institutionalised older people are not always
      specific. AIMS: To construct and verify an instrument with which to detect
      depression in elderly nursing home residents (NH-SDI). METHOD: Firstly for the
      construction, 328 elderly people were selected at random from the residents of 17
      nursing homes in France, and examined by a single investigator. The examination
      included a psychiatric assessment, an evaluation of cognitive function using the
      MMSE, an evaluation of depressive state using four different instruments (mini
      GDS, Goldberg, DMAS, CSDD), and assessment of any changes in behaviour in those
      suffering from dementia, using the NPI. A second stage was to confirm NH-SDI in
      99 institutionalised subjects. RESULTS: Following the selection of items, we
      created a scale of 16 dichotomous items (NH-SDI). The internal consistency was
      satisfactory (alpha Cronbach = 0.85), as was its reliability with a sensitivity
      of 85.1% and a specificity of 86.5% for a cut-off score above 5. CONCLUSIONS: The
      NH-SDI appears to be a useful instrument for the detection of depression in
      nursing homes and can easily be applied by healthcare staff as part of routine
      procedures.

PMID- 21744387
TI  - Homocysteine in Alzheimer's disease: role of dietary folate, vitamin B6 and B12.

PMID- 21744388
TI  - Unrecognized medical disorders among older patients in psychiatric emergency
      service.

PMID- 21744389
TI  - The clinical dementia rating scale could be helpful in differentiating
      frontotemporal dementia from Alzheimer's disease.

PMID- 21744390
TI  - Longitudinal stability of subsyndromal symptoms of depression in individuals with
      mild cognitive impairment: relationship to conversion to dementia after 3 years.
AB  - OBJECTIVE: To evaluate the degree to which longitudinal stability of subsyndromal
      symptoms of depression (SSD) is associated with conversion to dementia in
      patients with mild cognitive impairment (MCI). METHODS: Data from 405 MCI
      participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study
      were analyzed. Participants were evaluated at baseline and 12-month intervals
      over 3 years. Participants were designated as MCI converters if dementia was
      diagnosed within 3 years or as cognitively stable MCI if dementia was not
      diagnosed during this interval. SSD were evaluated utilizing the 15-item
      Geriatric Depression Scale (GDS). Endorsement of specific SSD at baseline and the
      stability of SSD over 36 months were compared between the two MCI groups.
      RESULTS: Baseline symptom endorsement and stability of total GDS scores did not
      differentiate MCI groups. Worsening of four individual items from the GDS over
      time (memory problems, feelings of helplessness, loss of interest, and preference
      for staying at home) differentiated MCI converters from cognitively stable MCI (p
      < 0.05 for all). However, only increased endorsement of memory symptoms over time
      was associated with progression to dementia after controlling for other clinical
      variables (p = 0.05). CONCLUSIONS: SSD in MCI participants largely consist of
      cognitive symptoms and activity limitations, and the stability of SSD over time
      differentiated the MCI groups better than baseline endorsement of symptoms.
      However, the only significant predictor of conversion to dementia was increased
      endorsement of memory problems, which likely represents insight into cognitive
      problems more than depressive symptomatology in MCI individuals.

PMID- 21744391
TI  - Estimating the pKa values of basic and acidic side chains in ion channels using
      electrophysiological recordings: a robust approach to an elusive problem.
AB  - As a step toward gaining a better understanding of the physicochemical bases of
      pK(a)-value shifts in ion channels, we have previously proposed a method for
      estimating the proton affinities of systematically engineered ionizable side
      chains from the kinetic analysis of single-channel current recordings. We
      reported that the open-channel current flowing through mutants of the (cation
      selective) muscle nicotinic acetylcholine receptor (AChR) engineered to bear
      single basic residues in the transmembrane portion of the pore domain fluctuates
      between two levels of conductance. Our observations were consistent with the idea
      that these fluctuations track directly the alternate protonation-deprotonation of
      basic side chains: protonation of the introduced basic group would attenuate the
      single-channel conductance, whereas its deprotonation would restore the wild-type
      like level. Thus, analysis of the kinetics of these transitions was interpreted
      to yield the pK(a) values of the substituted side chains. However, other
      mechanisms can be postulated that would also be consistent with some of our
      findings but according to which the kinetic analysis of the fluctuations would
      not yield true pK(a)s. Such mechanisms include the pH-dependent interconversion
      between two conformations of the channel that, while both ion permeable, would
      support different cation-conduction rates. In this article, we present
      experimental evidence for the notion that the fluctuations of the open-channel
      current observed for the muscle AChR result from the electrostatic interaction
      between fixed charges and the passing cations rather than from a change in
      conformation. Hence, we conclude that bona fide pK(a) values can be obtained from
      single-channel recordings.

PMID- 21744392
TI  - Quantitative use of chemical shifts for the modeling of protein complexes.
AB  - Despite recent advances in the modeling of protein-protein complexes by docking,
      additional information is often required to identify the best solutions. For this
      purpose, NMR data deliver valuable restraints that can be used in the sampling
      and/or the scoring stage, like in the data-driven docking approach HADDOCK that
      can make use of NMR chemical shift perturbation (CSP) data to define the binding
      site on each protein and drive the docking. We show here that a quantitative use
      of chemical shifts (CS) in the scoring stage can help to resolve ambiguities. A
      quantitative CS-RMSD score based on (1) H(alpha) ,(13) C(alpha) , and (15) N
      chemical shifts ranks the best solutions always at the top, as demonstrated on a
      small benchmark of four complexes. It is implemented in a new docking protocol,
      CS-HADDOCK, which combines CSP data as ambiguous interaction restraints in the
      sampling stage with the CS-RMSD score in the final scoring stage. This
      combination of qualitative and quantitative use of chemical shifts increases the
      reliability of data-driven docking for the structure determination of complexes
      from limited NMR data.

PMID- 21744393
TI  - On the development of protein pKa calculation algorithms.
AB  - Protein pK(a) calculation methods are developed partly to provide fast non
      experimental estimates of the ionization constants of protein side chains.
      However, the most significant reason for developing such methods is that a good
      pK(a) calculation method is presumed to provide an accurate physical model of
      protein electrostatics, which can be applied in methods for drug design, protein
      design, and other structure-based energy calculation methods. We explore the
      validity of this presumption by simulating the development of a pK(a) calculation
      method using artificial experimental data derived from a human-defined physical
      reality. We examine the ability of an RMSD-guided development protocol to
      retrieve the correct (artificial) physical reality and find that a rugged
      optimization landscape and a huge parameter space prevent the identification of
      the correct physical reality. We examine the importance of the training set in
      developing pK(a) calculation methods and investigate the effect of experimental
      noise on our ability to identify the correct physical reality, and find that both
      effects have a significant and detrimental impact on the physical reality of the
      optimal model identified. Our findings are of relevance to all structure-based
      methods for protein energy calculations and simulation, and have large
      implications for all types of current pK(a) calculation methods. Our analysis
      furthermore suggests that careful and extensive validation on many types of
      experimental data can go some way in making current models more realistic.

PMID- 21744394
TI  - Electrostatic pKa computations in proteins: role of internal cavities.
AB  - The solvent accessible surface area (SASA) algorithm is conventionally used to
      characterize protein surfaces in electrostatic energy computations of proteins.
      Unfortunately, it often fails to find narrow cavities inside a protein. As a
      consequence pK(a) computations based on this algorithm perform badly. In this
      study a new cavity-algorithm is introduced, which solves this problem and
      provides improved pK(a) values. The procedure is applied to 20 pK(a) values of
      titratable groups introduced as point mutations in SNase variants, where crystal
      structures are available. The computations of these pK(a)s are particular
      challenging, since they are placed in a rather hydrophobic environment. For nine
      mutants, where the titratable residue is in contact with a large cavity, the
      RMSD(pKa) between computed and measured pK(a) values is 2.04, which is a
      considerable improvement as compared to the original results obtained with
      Karlsberg(+) (http://agknapp.chemie.fu-berlin.de/karlsberg/) that yielded an
      RMSD(pKa) of 8.8. However, for 11 titratable residues the agreement with
      experiments remains poor (RMSD(pKa) = 6.01). Considering 15 pK(a)s of SNase,
      which are in a more conventional less hydrophobic protein environment, the
      RMSD(pKa) is 2.1 using the SASA-algorithm and 1.7 using the new cavity-algorithm.
      The agreement is reasonable but less good than what one would expect from the
      general performance of Karlsberg(+) indicating that SNase belongs to the more
      difficult proteins with respect to pK(a) computations. We discuss the possible
      reasons for the remaining discrepancies between computed and measured pK(a)s.

PMID- 21744395
TI  - Developing hybrid approaches to predict pKa values of ionizable groups.
AB  - Accurate predictions of pKa values of titratable groups require taking into
      account all relevant processes associated with the ionization/deionization.
      Frequently, however, the ionization does not involve significant structural
      changes and the dominating effects are purely electrostatic in origin allowing
      accurate predictions to be made based on the electrostatic energy difference
      between ionized and neutral forms alone using a static structure and the subtle
      structural changes be accounted by using dielectric constant larger than two. On
      another hand, if the change of the charge state is accompanied by a large
      structural reorganization of the target protein, then the relevant conformational
      changes have to be explicitly taken into account in the pKa calculations. Here we
      report a hybrid approach that first predicts the titratable groups whose
      ionization is expected to cause large conformational changes, termed
      "problematic" residues, and then applies a special protocol on them, while the
      rest of the pK(a)s are predicted with rigid backbone approach as implemented in
      multi-conformation continuum electrostatics (MCCE) method. The backbone
      representative conformations for "problematic" groups are generated with either
      molecular dynamics simulations with charged and uncharged amino acid or with ab
      initio local segment modeling. The corresponding ensembles are then used to
      calculate the titration curves of the "problematic" residues and then the results
      are averaged to obtain the corresponding pKa.

PMID- 21744396
TI  - Type II proatlantal artery (occipital subtype) with bilateral absence of the
      vertebral arteries.

PMID- 21744397
TI  - Arterial anatomy of the gracilis muscle as determined by latex injection and
      glycerin transparency.
AB  - The gracilis muscle is widely used in reconstructive surgery, either as a
      pedicled flap or as a free microsurgical flap. The aim of this study was to
      demonstrate in detail the arterial anatomy of the gracilis muscle, particularly
      its intramuscular artery distribution, by using a method involving red latex
      injection and glycerin transparency, which makes muscle tissues quite transparent
      and allows direct visualization of the arterial anatomy. Twenty-four specimens of
      gracilis muscle were harvested after injecting 12 cadavers with red latex. The
      different patterns of blood supply of the gracilis muscle were counted. A
      complete arterial system formed by anastomoses of intramuscular arterial branches
      was observed in each specimen. The existence of several arterial branches at the
      proximal origin of each muscle was observed. The results of this study provide
      reconstructive surgeons with useful information regarding gracilis muscle flap
      design.

PMID- 21744398
TI  - Four-coordinate trispyrazolylboratomanganese and -iron complexes with a
      pyrazolato co-ligand: syntheses and properties as oxidation catalysts.
AB  - A series of complexes of the type [(Tp(R1,R2))M(X)] (Tp = trispyrazolylborato)
      with R(1)/R(2) combinations Me/tBu, Ph/Me, iPr/iPr, Me/Me and for M = Mn or Fe
      coordinating [Pz(Me,tBu)](-) (Pz = pyrazolato) or Cl(-) as co-ligand X has been
      synthesised. Although the chloride complexes were very unreactive and stable in
      air, the pyrazolato series was far more reactive in contact with oxidants like
      O(2) and tBuOOH. The [(Tp(R1,R2))M(Pz(Me,tBu))] complexes proved to be active pre
      catalysts for the oxidation of cyclohexene with tBuOOH, reaching turnover
      frequencies (TOFs) ranging between moderate and good in comparison to other
      manganese catalysts. Cyclohexene-3-one and cyclohexene-3-ol were always found to
      represent the main products, with cyclohexene oxide occasionally formed as a side
      product. The ratios of the different oxidation products varied with the reaction
      conditions: in the case of a peroxide/alkene ratio of 4:1, considerably more
      ketone than alcohol was obtained and cyclohexene oxide formation was almost
      negligible, whereas a ratio of 1:10 led to a significant increase of the alcohol
      proportion and to the formation of at least small amounts of the epoxide. Pre
      treatment of the dissolved [(Tp(R1,R2))M(Pz(Me,tBu))] pre-catalysts with O(2) led
      to product distributions and TOFs that were very similar to those found in the
      absence of O(2), so that it may be argued that tBuOOH and O(2) both lead to the
      same active species. The results of EPR spectroscopy and ESI-MS suggest that the
      initial product of the reaction of [(Tp(Me,Me))Mn(Pz(Me,tBu))] with O(2) contains
      a Mn(III)(O)(2)Mn(IV) core. Prolonged exposure to O(2) leads to a different
      dinuclear complex containing three O-bridges and resulting in different
      TOFs/product distributions. Analogous findings were made for other complexes and
      formation of these overoxidised products may explain the deviation of the
      catalytic performances if the reactions are carried out in an O(2) atmosphere.

PMID- 21744399
TI  - Design of cross-linked semicrystalline poly(epsilon-caprolactone)-based networks
      with one-way and two-way shape-memory properties through Diels-Alder reactions.
AB  - Cross-linked poly(epsilon-caprolactone) (PCL)-based polyesterurethane (PUR)
      systems have been synthesized through Diels-Alder reactions by reactive
      extrusion. The Diels-Alder and retro-Diels-Alder reactions proved to be useful
      for enhancing the molecular motion of PCL-based systems, and therefore their
      crystallization ability, in the design of cross-linked semicrystalline polymers
      with one-way and two-way shape-memory properties. Successive reactions between
      alpha,omega-diol PCL (PCL(2) ), furfuryl alcohol, and methylene diphenyl 4,4'
      diisocyanate straightforwardly afforded the alpha,omega-furfuryl PCL-based PUR
      systems, and subsequent Diels-Alder reactions with N,N-phenylenedimaleimide
      afforded the thermoreversible cycloadducts. The cross-linking density could be
      modulated by partially replacing PCL-diol with PCL-tetraol. Interestingly, the
      resulting PUR systems proved to be semicrystalline cross-linked polymers, the
      melting temperature of which (close to 45  degrees C) represented the switching
      temperature for their shape-memory properties. Qualitative and quantitative
      measurements demonstrated that these PUR systems exhibited one-way and two-way
      shape-memory properties depending on their cross-linking density.

PMID- 21744400
TI  - General synthesis of hybrid TiO2 mesoporous "french fries" toward improved
      photocatalytic conversion of CO2 into hydrocarbon fuel: a case of TiO2/ZnO.

PMID- 21744401
TI  - A label-free gold-nanoparticle-based SERS assay for direct cyanide detection at
      the parts-per-trillion level.
AB  - Cyanide is an extremely toxic lethal poison known to humankind. Developing rapid,
      highly sensitive, and selective detection of cyanide from water samples is
      extremely essential for human life safety. Driven by the need, here we report a
      gold-nanoparticle-based label-free surface-enhanced Raman spectroscopy (SERS)
      system for highly toxic cyanide ion recognition in parts-per-trillion level and
      to examine gold-nanoparticle-cyanide interaction. We have shown that the SERS
      assay can be used to probe the gold nanoparticle dissociation process in the
      presence of cyanide ions. Our experimental data indicates that gold-nanoparticle
      based SERS can detect cyanide from a water sample at the 110 ppt level with
      excellent discrimination against other common anions and cations. The results
      also show that the SERS probe can be used to detect cyanide from environmental
      samples.

PMID- 21744402
TI  - Stereoselective hydrosilylation of enals and enones catalysed by palladium
      nanoparticles.
AB  - A highly versatile and efficient hydrosilylation method by palladium nanoparticle
      catalysis allows the direct and chemoselective synthesis of 1) enolsilanes of
      high isomeric purity, 2) saturated aldehydes or ketones, or 3) the corresponding
      saturated acetals from alpha,beta-unsaturated aldehydes or ketones. The choice of
      the product is determined by simply switching the solvent from THF to mixtures of
      THF/water or THF/alcohol.

PMID- 21744403
TI  - Mobius aromatic [28]hexaphyrin phosphonium adducts.

PMID- 21744404
TI  - Gold(I)-catalyzed tandem oxidative ring-opening/C-C bond cleavage reactions of
      vinylidenecyclopropanes with secondary amines under an oxygen atmosphere.

PMID- 21744405
TI  - Samarium diiodide induced cyclizations of gamma-, delta- and epsilon-indolyl
      ketones: reductive coupling, intermolecular trapping, and subsequent
      transformations of indolines.
AB  - This comprehensive study describes our results of samarium diiodide induced 5-exo
      trig to 8-exo-trig cyclization/alkylation sequences of 3'-acceptor-substituted
      indolyl ketones. All cyclization precursors were easily prepared by simple N
      alkylation or N-acylation of indole derivatives with the corresponding iodo
      alkanones, acid chlorides, or lactones. After treatment of indolyl ketones with
      two equivalents of SmI(2), the generated stabilized carbanionic intermediates
      were trapped with different electrophiles leading to a variety of highly
      substituted indoline derivatives in good to very good yields. In general, the
      cyclization products were obtained as single diastereomers bearing a newly
      generated quaternary center, a common structural motif in various indole
      alkaloids. The relative configurations of the products were established by NOE
      experiments and by single-crystal analysis and follow the rules already
      established. Furthermore, the obtained products were subjected to a series of
      chemical transformations, such as oxidation, reduction, and metathesis reactions
      resulting in a range of interesting synthetic building blocks valuable for
      further applications.

PMID- 21744406
TI  - Click chemistry for the assembly of gold nanorods and silver nanoparticles.

PMID- 21744407
TI  - Nickel-catalyzed C-H arylation of azoles with haloarenes: scope, mechanism, and
      applications to the synthesis of bioactive molecules.
AB  - Novel nickel-based catalytic systems for the C-H arylation of azoles with
      haloarenes and aryl triflates have been developed. We have established that
      Ni(OAc)(2)/bipy/LiOtBu serves as a general catalytic system for the coupling with
      aryl bromides and iodides as aryl electrophiles. For couplings with more
      challenging electrophiles, such as aryl chlorides and triflates, the
      Ni(OAc)(2)/dppf (dppf = 1,1'-bis(diphenylphosphino)ferrocene) system was found to
      be effective. Thiazoles, benzothiazoles, oxazoles, benzoxazoles, and
      benzimidazoles can be used as the heteroarene coupling partner. Upon further
      investigation, we discovered a new protocol for the present coupling using
      Mg(OtBu)(2) as a milder and less expensive alternative to LiOtBu. Attempts to
      reveal the mechanism of this nickel-catalyzed heterobiaryl coupling are also
      described. This newly developed methodology has been successfully applied to the
      syntheses of febuxostat (a xanthine oxidase inhibitor that is effective for the
      treatment of gout and hyperuricemia), tafamidis (effective for the treatment of
      TTR amyloid polyneuropathy), and texaline (a natural product having
      antitubercular activity).

PMID- 21744408
TI  - Active site design in a core-shell nanostructured catalyst for a one-pot
      oxidation reaction.

PMID- 21744409
TI  - Asymmetric trienamine catalysis for the construction of structurally rigid cyclic
      alpha,alpha-disubstituted amino acid derivatives.

PMID- 21744410
TI  - Factors related to criminal justice expenditure trajectories for adults with
      serious mental illness.
AB  - BACKGROUND: Criminal careers have been extensively studied in general population
      sample, but less is known about such patterns among people with major mental
      illness, and where so, criminal justice expenditure has not been taken into
      account. AIMS: Our aim was to examine criminal justice system expenditure over
      time in one Florida county. Our main research question was whether treatment for
      mental disorders was related to a change in criminal offending and expenditure
      trajectory. METHODS: We used the Pinellas County (Florida) Criminal Justice
      Information System to identify individuals under age 65 arrested between July
      2003 and June 2004. Archival medical service, social and homeless services data
      were used to identify individuals with a serious mental illness. A two-step
      analysis was used to examine the data: first, we identified groups of people with
      similar patterns of criminal justice expenditures over 4 years (July 2002 to June
      2006); second, we evaluated their demographic characteristics, diagnosis and
      treatment as potential predictors of group membership. RESULTS: Three thousand
      seven hundred sixty-nine people with serious mental illness were identified in
      the Pinellas County jail population. Their average length of stay in jail was 151
      days and in prison was 48 days. The trajectory analysis identified three groups
      of individuals with distinct trajectories of criminal justice expenditures: those
      with low stable, those with initially high but decreasing and those with
      initially high and sustained or increasing. Mental health treatment, whether
      acute or sustained, voluntary or mandatory, was associated with membership of the
      low stable group. CONCLUSION: Review of criminal justice expenditure over time on
      individuals with major mental disorder may provide important indicators of unmet
      need for mental health services. Furthermore, it seems probable that improved
      provision of such services for them could reduce recidivism as well as improving
      health. Interventions may also be better focused if criminal justice expenditure
      trajectories are examined; programmes targeting re-offending as well as specific
      mental health problems may be most effective.

PMID- 21744411
TI  - Milestones to recovery: preliminary validation of a framework to promote recovery
      and map progress through the medium secure inpatient pathway.
AB  - BACKGROUND: Forensic mental health care in the UK has undergone a rapid expansion
      since the late 1990s. In medium secure units (MSUs), there is growing emphasis on
      developing care pathways without much theoretical underpinning. We developed a
      concept of 'Milestones to Recovery' (MTR) to measure progress through the MSU
      pathway. AIMS: Our aim was to validate the MTR framework. Our hypotheses were
      that patients scoring higher on the MTR Scale would be more likely to be
      aggressive to others in the following 6 months and resident in the acute areas of
      the unit and that those scoring lower would be more likely to be discharged
      within 6 months of the assessment. METHODS: An MTR scale was developed to enable
      the investigation of the validity of the MTR framework and evaluated with staff
      evaluations of 80 resident patients using a prospective, longitudinal and
      naturalistic design. RESULTS: The results suggest that the MTR framework is valid
      in discriminating between different stages on the MSU pathway. Therapeutic
      engagement was particularly important in terms of progress through the MSU,
      whereas current behaviour was important in predicting future aggression.
      CONCLUSIONS: Further research is required to test the MTR framework across
      different levels of security, with larger samples and within different
      populations. IMPLICATIONS FOR PRACTICE: Provides a framework to map progress
      through the service. Identifies key factors that influence recovery and
      rehabilitation. Potential to promote dialogue between patients and staff, and
      enhance motivation.

PMID- 21744412
TI  - "Know thyself".

PMID- 21744413
TI  - Characterization and subcellular localization of Tektin 3 in rat spermatozoa.
AB  - Mammalian sperm flagella have filament-forming Tektin proteins (Tektin 1-5)
      reported to be involved in the stability and structural complexity of flagella.
      Male mice null for Tektin3 produce spermatozoa with reduced forward progression
      and increased flagellar structural bending defects. The subcellular localization
      of Tektin3 (TEKT3) in spermatozoa, however, has not been clarified at the
      ultrastructural level. To elucidate the molecular localization of TEKT3 in
      flagella of rat spermatozoa, we performed extraction studies followed by
      immunoblot analysis, immunofluorescence microscopy, and immunogold electron
      microscopy. Extraction of sperm flagella from the cauda epididymis resulted in
      complete removal of axonemal tubulins, while TEKT3 was resistant to extraction
      with the same S-EDTA (1% SDS, 75 mM NaCl, 24 mM EDTA, pH 7.6) solution,
      suggesting that TEKT3 might be present in the peri-axonemal component and not
      directly associated with axonemal tubulins. Resistance to S-EDTA extraction might
      be due to disulfide bond formation during epididymal maturation since
      concentrations of DTT greater than 5 mM drastically promoted release of TEKT3
      from flagella. Immunofluorescence microscopy and pre-embedding immunoelectron
      microscopy revealed that TEKT3 was predominantly associated with the surface of
      mitochondria and outer dense fibers in the middle piece. In addition, TEKT3 was
      found to be present at the equatorial segment region of the acrosome membrane in
      sperm heads. TEKT3 might not only work as a flagellar constituent required for
      flagellar stability and sperm motility but also may be involved in acrosome
      related events, such as the acrosome reaction or sperm-egg fusion.

PMID- 21744414
TI  - Selection of irrigation fluid to eradicate free cancer cells during head and neck
      cancer surgery.
AB  - BACKGROUND: Free cancer cells can be spilled out from exposed tumors or ruptured
      tumors. We examined the cytocidal effect of various irrigation fluids on free
      cancer cells in an animal wound model mimicking head and neck surgery. METHODS:
      Cancer cell-contaminated wounds were made with C3H/HeJ mice and syngeneic
      squamous cell carcinoma (SCC VII) cells. Distilled water, 5% povidone-iodine,
      1.5% H(2)O(2), normal saline, and cisplatin were used to irrigate for 5 minutes.
      In vitro tumor growth assays were done with different concentrations and exposure
      times of povidone-iodine and distilled water. RESULTS: In the animal study,
      povidone-iodine significantly inhibited tumor growth. Povidone-iodine caused
      substantial inhibition of in vitro tumor growth, even at the concentration of
      0.05%. After 30 seconds of exposure to 1% povidone-iodine, cancer cells were
      completely inhibited. CONCLUSIONS: Povidone-iodine could be selected
      preferentially for the irrigation fluid during head and neck surgery, especially
      when the wound is suspected of cancer cell contamination.

PMID- 21744415
TI  - Risk of falls associated with antihypertensive medication: self-controlled case
      series.
AB  - PURPOSE: To quantify the possible role of confounding in our earlier estimates of
      the risk of falls amongst older people who have been prescribed
      antihypertensives. METHODS: Self-controlled case series analysis of 9862
      individuals older than 60 years of age with a first fall recorded between years
      2003 and 2006 and at least 12 months of recorded history before the first fall,
      taken from 386 UK general practices contributing data to The Health Improvement
      Network primary care database. Conditional Poisson regression to estimate
      incidence rate ratios for periods of exposure and non-exposure, adjusting for the
      effect of age. RESULTS: Incidence rate ratio of first fall in days 1-21 of the
      first episode of thiazide prescription is 2.80 (95%CI 1.7-4.57). For beta
      blockers, the rate ratio in day 22 onwards is 1.23 (95%CI 1.02-1.48) in the very
      first episode of medication and 1.21 (95%CI 1.02-1.42) in subsequent episodes but
      is not significant in other periods of exposure. The incidence rate of first
      falls in day 22 of any episode of calcium channel blocker prescription is 0.75
      (95%CI 0.60-0.92). CONCLUSIONS: The study provides evidence that at least some of
      our earlier estimates were subject to confounding. Nevertheless, thiazide
      prescription remains associated with an increased risk of first fall, and this
      effect is strongest in the first 3 weeks of prescription. Our study demonstrates
      that the case series method provides an effective way to assess the extent of
      residual confounding in case-control studies.

PMID- 21744416
TI  - Effect of fluoro substitution on the fragmentation of the K-shell excited/ionized
      pyridine studied by electron impact.
AB  - Fragmentation of the pyridine ring followed by K-shell excitation/ionization has
      been studied with 2-fluoropyridine (2FPy) by electron impact. Ab initio molecular
      orbital (MO) calculations were also carried out to investigate the electronic
      states correlating with specific fragment ions. The fragment ions are produced
      characteristically at the N 1s edge, while the spectra observed at the F 1s and C
      1s edges exhibit a small difference from that at the valence ionization. The
      production of the C(4)H(2)(+), C(4)H(3)(+) and C(4)H(2)F(+) ions indicates that
      the cleavage of the N-C6 and C2-C3 bonds or the N-C2 and C5-C6 bonds is likely to
      occur after the N 1s excitation/ionization. Ab initio MO calculations indicate
      that the former fission is likely to proceed through the n(N)(1)pi(2)(1)pi(3)(2)
      and n(N)(0)pi(2)(2)pi(3)(2) excited states of the parent molecular dication. On
      the other hand, the breakage of the N-C2 and C4-C5 bonds, which specifically
      proceeds at the N 1s edge for 2-methylpyridine, does not occur for 2FPy. The
      present calculation reveals that the products of this channel are unstable by the
      electronegativity of fluorine and that the relative energy of the Auger-final
      states of 2FPy is lowered by the reorganization and electron correlation effects.

PMID- 21744417
TI  - Application of MALDI TOF/TOF mass spectrometry and collision-induced dissociation
      for the identification of disulfide-bonded peptides.
AB  - This paper describes a method for the fast identification and composition of
      disulfide-bonded peptides. A unique fragmentation signature of inter-disulfide
      bonded peptides is detected using matrix-assisted laser desorption/ionization
      (MALDI) time-of-flight (TOF)/TOF mass spectrometry and high-energy collision
      induced dissociation (CID). This fragmentation pattern identifies peptides with
      an interconnected disulfide bond and provides information regarding the
      composition of the peptides involved in the pairing. The distinctive signature
      produced using CID is a triplet of ions resulting from the cleavage of the
      disulfide bond to produce dehydroalanine, cysteine or thiocysteine product ions.
      This method is not applicable to intra-peptide disulfide bonds, as the cleavage
      mechanism is not the same and a triplet pattern is not observed. This method has
      been successfully applied to identifying disulfide-bonded peptides in a number of
      control digestions, as well as study samples where disulfide bond networks were
      postulated and/or unknown.

PMID- 21744418
TI  - Heparin-like glycosaminoglycan/amine salt-bridge interactions: a new potential
      tool for HLGAGs analysis using mass spectrometry.
AB  - Characterization of glycosaminoglycans poses a challenge for current analytical
      techniques, as they are highly acidic, polydisperse and heterogeneous compounds.
      The purpose of this study is the separation and analysis of a partially
      depolymerized heparin-like glycosaminoglycan by on-line ion-pairing reversed
      phase high-performance liquid chromatography/electrospray mass spectrometry. The
      gas-phase behavior of two synthesized glycosaminoglycans has been investigated.
      Dibutylamine was found to be the best suited ion-pairing reagents for mass
      spectrometry analysis. The optimized ion-pairing conditions provide reproducible
      and easily interpretable electrospray mass spectra in both negative and positive
      ESI modes. The glycosaminoglycans are detected as a non-covalent complex with
      amines. In fact, the observed ionic species and their gas-phase dissociation
      under CID conditions revealed the presence of salt bridge interactions in the gas
      phase.

PMID- 21744419
TI  - MALDI-TOFMS analysis of coordination and organometallic complexes: a nic(h)e area
      to work in.
AB  - A mini-review of the characterisation of metal-containing compounds by matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI
      TOFMS) is presented. Organometallic and coordination compounds have many varied
      applications, most notably in industrial catalytic processes and also in the
      electronics and healthcare sectors. In general, the compounds discussed, be they
      small or large molecules, have a high percentage metal content, rather than
      simply containing 'a metal atom'. A brief history of the field is given, but the
      main scope over the last 5 years is covered in some detail. How MALDI-TOFMS
      compliments electrospray for metal-containing compounds is highlighted.
      Perspectives on recent advances, such as solvent-free and air/moisture-sensitive
      sample preparation, and potential future challenges and developments, such as
      nanomaterials and metallodrug/metallometabolite imaging, are given.

PMID- 21744420
TI  - Antimicrobial peptide response to blood translocation of bacterial DNA in Crohn's
      disease is affected by NOD2/CARD15 genotype.
AB  - BACKGROUND: Blood translocation of bacterial-DNA has been described in patients
      with Crohn's disease (CD). The host's immune cell types cooperate to respond
      against bacterial insults. Some antimicrobial peptides are inducible after
      culture with bacterial products and a linkage has been established between them
      and NOD2/CARD15. The aim was to test whether defensins and cathelicidin (LL-37)
      expression and NOD2/CARD15 mutations in blood neutrophils are related to
      molecular bacterial translocation events in CD patients. METHODS: Fifty
      consecutively admitted CD patients and 15 healthy controls were included.
      Clinical and analytical characteristics of patients were considered. NOD2/CARD15
      genotyping, presence of bacterial-DNA, defensin and cathelicidin gene, and
      protein levels in neutrophils and serum cytokine levels were studied. RESULTS:
      Twenty patients (40%) presented bacterial-DNA in blood. Eleven were active and 9
      were in remission. Bacterial-DNA was not present in controls. NOD2/CARD15
      mutations were identified in 25 patients (50%), 15 of which were in remission.
      Sixty percent of bacterial-DNA(+) and 43% of bacterial-DNA(-) patients showed a
      NOD2/CARD15 mutation. beta-Defensin 2 and LL-37 mRNA and protein levels were
      upregulated in bacterial-DNA(+) patients. beta-Defensin 2 and LL-37 expression
      correlated with bacterial-DNA concentration only in patients with a wildtype
      NOD2/CARD15 genotype. Cultured neutrophils of bacterial-DNA(-) patients confirmed
      the muramyl dipeptide-independent association between DEFB2 and LL-37 with
      bacterial-DNA concentration in wildtype NOD2/CARD15 patients. Cytokine levels
      were increased in bacterial-DNA(+) patients and correlated with bacterial-DNA
      concentration. NOD2/CARD15 genotype did not influence this correlation.
      CONCLUSIONS: beta-Defensin 2, LL-37, and proinflammatory cytokines are increased
      in CD patients with bacterial-DNA in a concentration-dependent manner.
      NOD2/CARD15 plays a key role in the regulation of this response.

PMID- 21744421
TI  - The atypical cannabinoid O-1602 protects against experimental colitis and
      inhibits neutrophil recruitment.
AB  - BACKGROUND: Cannabinoids are known to reduce intestinal inflammation. Atypical
      cannabinoids produce pharmacological effects via unidentified targets. We were
      interested in whether the atypical cannabinoid O-1602, reportedly an agonist of
      the putative cannabinoid receptor GPR55, reduces disease severity of dextran
      sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS)-induced colitis in
      C57BL/6N and CD1 mice. METHODS: DSS (2.5% and 4%) was supplied in drinking water
      for 1 week while TNBS (4 mg) was applied as a single intrarectal bolus. RESULTS:
      Both treatments caused severe colitis. Injection of O-1602 (5 mg/kg
      intraperitoneally) significantly reduced macroscopic and histological colitis
      scores, and myeloperoxidase activity. The protective effect was still present in
      cannabinoid receptor 1 (CB1) and 2 (CB2) double knockout mice and mice lacking
      the GPR55 gene. To investigate a potential mechanism underlying the protection by
      O-1602 we performed neutrophil chemotactic assays. O-1602 concentration
      dependently inhibited migration of murine neutrophils to keratinocyte-derived
      chemokine (KC), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and the N-formyl
      peptide receptor ligand WKYMVm. The inhibitory effect of O-1602 was preserved in
      neutrophils from CB1/CB2 double knockout and GPR55 knockout mice. No differences
      were seen in locomotor activity between O-1602-treated and control mice,
      indicating lack of central sedation by this compound. CONCLUSIONS: Our data
      demonstrate that O-1602 is protective against experimentally induced colitis and
      inhibits neutrophil recruitment independently of CB1, CB2, and GPR55 receptors.
      Thus, atypical cannabinoids represent a novel class of therapeutics that may be
      useful for the treatment of inflammatory bowel diseases.

PMID- 21744422
TI  - Oxidative state and IL-6 production in intestinal myofibroblasts of Crohn's
      disease patients.
AB  - BACKGROUND: Intestinal subepithelial myofibroblasts (ISEMFs) produce inflammatory
      cytokines in response to certain stimuli. In the intestine of patients with
      Crohn's disease (CD), cytokine synthesis is modified and an increased number of
      myofibroblasts has been observed. The intracellular redox state influences
      cytokine production and oxidative stress is present in the intestinal mucosa of
      CD patients. METHODS: This study was performed in ISEMFs isolated from the colon
      of patients with active CD and in a myofibroblast cell line derived from human
      colonic mucosa: 18Co cells. Cellular glutathione (GSH) levels were modulated by
      treatment with buthionine sulfoximine, an inhibitor of GSH synthesis, or N
      acetylcysteine, a GSH precursor. GSH and oxidized glutathione (GSSG) levels were
      measured by high-performance liquid chromatography (HPLC) methods. Interleukin
      (IL)-6 production was detected by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: ISEMFs of CD patients exhibited an increased oxidative state due to a
      decrease in the GSH/GSSG ratio, which is related to an increase in basal IL-6
      production or is stimulated by tumor necrosis factor alpha (TNFalpha) or
      bacterial products. This relationship was also confirmed in 18Co cells.
      Phosphorylation and activation of ERK1/2 and p38 MAPK, which are signaling
      factors involved in the IL-6 synthesis, were also increased when there is
      oxidative stress in ISEMFs. CONCLUSIONS: This study shows for the first time in
      ISEMFs of CD patients an increased production of IL-6 synthesis related to the
      decrease in the GSH/GSSH ratio, suggesting redox regulation with the involvement
      of specific kinase activation. The present data shed light on the pathogenesis of
      inflammatory chronic processes and relapses that occur in this pathology.

PMID- 21744423
TI  - Protein kinase C iota in the intestinal epithelium protects against dextran
      sodium sulfate-induced colitis.
AB  - BACKGROUND: The integrity of the intestinal epithelium is critical for the
      absorption and retention of fluid and nutrients. The intestinal epithelium also
      provides a barrier between the intestinal bacteria and the body's immune
      surveillance. Therefore, intestinal epithelial barrier function is critically
      important, and disruption of the intestinal epithelium results in rapid repair of
      the damaged area. METHODS: We evaluated the requirement for protein kinase C iota
      (PKCiota) in intestinal epithelial homeostasis and response to epithelial damage
      using a well-characterized mouse model of colitis. Mice were analyzed for the
      clinical, histological, and cellular effects of dextran sodium sulfate (DSS)
      treatment. RESULTS: Knockout of the mouse PKCiota gene (Prkci) in the intestinal
      epithelium (Prkci KO mice) had no effect on normal colonic homeostasis; however,
      Prkci KO mice were significantly more sensitive to DSS-induced colitis and death.
      After withdrawal of DSS, Prkci KO mice exhibited a continued increase in
      apoptosis, inflammation, and damage to the intestinal microvasculature and a
      progressive loss of trefoil factor 3 (TFF3) expression, a regulatory peptide
      important for intestinal wound healing. Knockdown of PKCiota expression in HT-29
      cells reduced wound healing and TFF3 expression, while addition of exogenous TFF3
      restored wound healing in PKCiota-depleted cells. CONCLUSIONS: Expression of
      PKCiota in the intestinal epithelium protects against DSS-induced colitis. Our
      data suggest that PKCiota reduces DSS-induced damage by promoting intestinal
      epithelial wound healing through the control of TFF3 expression.

PMID- 21744424
TI  - Impact of disrupting adenosine A3 receptors (A3-/- AR) on colonic motility or
      progression of colitis in the mouse.
AB  - BACKGROUND: Pharmacological studies suggest that adenosine A3AR influences
      motility and colitis. Functional A3-/-AR knockout mice were used to prove whether
      A3AR activation is involved in modulating either motility or colitis. METHODS:
      A3AR was probed by polymerase chain reaction (PCR) genotyping, Western blot, and
      immunochemistry. Motility was assessed in vivo by artificial bead-expulsion,
      stool-frequency, and FITC-dextran transit. Colitis was induced with dextran
      sodium sulfate (DSS) in A3-/-AR or wildtype (WT) age- and sex-matched controls.
      Progression of colitis was evaluated by histopathology, changes in
      myeloperoxidase (MPO), colon length, CD4(+) -cells, weight-loss, diarrhea, and
      the guaiac test. RESULTS: Goat anti-hu-A3 antiserum identified a 66 kDa
      immunogenic band in colon. A3AR-immunoreactivity is expressed in SYN(+) -nerve
      varicosities, s-100(+) -glia, and crypt cells, but not 5-HT(+) (EC), CD4(+) (T),
      tryptase(+) (MC), or muscle cells. A3AR immunoreactivity in myenteric ganglia of
      distal colon >> proximal colon by a ratio of 2:1. Intestinal transit and bead
      expulsion were accelerated in A3-/-AR mice compared to WT; stool retention was
      lower by 40%-60% and stool frequency by 67%. DSS downregulated A3AR in epithelia.
      DSS histopathology scores indicated less mucosal damage in AA3-/-AR mice than WT.
      A3-/-AR phenotype protected against DSS-induced weight loss, neutrophil (MPO), or
      CD4(+) -T cell infiltration, colon shortening, change in splenic weight,
      diarrhea, or occult-fecal blood. CONCLUSIONS: Functional disruption of A3AR in A3
      /-AR mice alters intestinal motility. We postulate that ongoing release of
      adenosine and activation of presynaptic-inhibitory A3AR can slow down transit and
      inhibit the defecation reflex. A3AR may be involved in gliotransmission. In
      separate studies, A3-/-AR protects against DSS colitis, consistent with a novel
      hypothesis that A3AR activation contributes to development of colitis.

PMID- 21744425
TI  - HNF4alpha and CDH1 are associated with ulcerative colitis in a Dutch cohort.
AB  - BACKGROUND: Inflammatory bowel diseases (IBDs), consisting of ulcerative colitis
      (UC) and Crohn's disease (CD), are complex disorders with multiple genes
      contributing to disease pathogenesis. A recent genome-wide association scan
      identified three novel susceptibility loci for UC: HNF4alpha, CDH1, and LAMB1. We
      performed an analysis of these three loci in an independent cohort. METHODS: In
      all, 821 UC patients and 1260 healthy controls of central European Caucasian
      descent were genotyped for single nucleotide polymorphisms (SNPs): rs6017342
      (HNF4alpha), rs1728785 (CDH1), and rs6949033 (LAMB1). Differences in allele and
      genotype distribution in cases and controls were tested for significance with the
      chi2 test. RESULTS: Allelic association analysis showed that SNP rs6017342 in the
      HNF4alpha locus was strongly associated with UC (P = 1,04 * 10(-11) , odds ratio
      [OR] = 1.56, 95% confidence interval [CI] = 1.37-1.77) and SNP rs1728785 (CDH1)
      was associated with P = 0.01 (OR = 1.23, 95% CI = 1.05-1.44). SNP rs6949033 in
      LAMB1 was not associated in our cohort (P = 0.12, OR = 1.11, 95% CI = 0.97-1.26).
      We found an association for SNP rs6949033 (LAMB1) for disease limited to the
      rectum (P = 0.02). However, this association was lost after correcting for
      multiple testing. No further specific subphenotype associations were identified.
      CONCLUSIONS: This is the first independent study to replicate the HNF4alpha and
      CDH1 loci as susceptibility loci for UC. The main candidate genes in these risk
      loci play important roles in the maintenance of the integrity of the epithelial
      barrier, highlighting the importance of the mucosal barrier function for UC
      pathogenesis.

PMID- 21744426
TI  - Blood-based biomarkers can differentiate ulcerative colitis from Crohn's disease
      and noninflammatory diarrhea.
AB  - BACKGROUND: Blood gene expression profiling has been used in several studies to
      identify patients with a number of conditions and diseases. A blood test with the
      ability to differentiate Crohn's disease (CD) from ulcerative colitis (UC) and
      noninflammatory diarrhea would be useful in the clinical management of these
      diseases. METHODS: Affymetrix U133Plus 2.0 GeneChip oligonucleotide arrays were
      used to generate whole blood gene expression profiles for 21 patients with UC, 24
      patients with CD, and 10 control patients with diarrhea, but without colonic
      pathology. RESULTS: A supervised learning method (logistic regression) was used
      to identify specific panels of probe sets which were able to discriminate between
      UC and CD and from controls. The UC panel consisted of the four genes, CD300A,
      KPNA4, IL1R2, and ELAVL1; the CD panel comprised the four genes CAP1, BID, NIT2,
      and NPL. These panels clearly differentiated between CD and UC. CONCLUSIONS: Gene
      expression profiles from blood can differentiate patients with CD from those with
      UC and from noninflammatory diarrheal disorders.

PMID- 21744427
TI  - Fecal osteoprotegerin may guide the introduction of second-line therapy in
      hospitalized children with ulcerative colitis.
AB  - BACKGROUND: Osteoprotegerin (OPG) is increased in inflamed colonic mucosa and has
      a role in immune regulation and apoptosis resistance. Fecal OPG may be useful in
      predicting corticosteroid resistance in hospitalized children with severe
      ulcerative colitis (UC). We aimed to determine whether fecal OPG predicts the
      need for second-line therapies in children hospitalized for UC. METHODS: We
      included 83 children with UC admitted for intravenous corticosteroid treatment.
      Children were classified as responders/nonresponders based on the need for
      therapy escalation. Fecal OPG results were compared with those of four other
      fecal markers. RESULTS: Of the enrolled children, seven had day 1 samples only,
      53 children had day 3 samples only, and 23 had both. Twenty-two children failed
      corticosteroid therapy and required infliximab (n = 20) or colectomy (n = 2). On
      the third treatment day the median fecal OPG levels were significantly higher in
      the nonresponders group compared with the responders: 77 pmol/L (interquartile
      range [IQR] 27-137) versus 13 pmol/L (3-109); P = 0.007. The best day 3 fecal OPG
      cutoff to predict second-line therapy was >50 pmol/L with a sensitivity of 71%
      and specificity of 69% (area under the receiver operator curve [ROC] of 0.70%-95%
      confidence interval [CI] 0.57-0.82). Fecal OPG was superior to day 3 fecal
      calprotectin, lactoferrin, and S100A12 as a predictor of corticosteroid
      nonresponse, but equivalent to the less commonly used M2-pyruvate kinase.
      CONCLUSIONS: Day 3 fecal OPG may guide the decision to institute second-line
      therapy in children with severe UC. The role of OPG in the inflammatory response
      in pediatric UC deserves further study.

PMID- 21744428
TI  - Steroid dependency and pediatric inflammatory bowel disease in the era of
      immunomodulators--a population-based study.
AB  - BACKGROUND: The aim was to investigate the impact of systemic steroid treatment
      (SST) and immunomodulators (IM) on disease course in children with inflammatory
      bowel disease (IBD). METHODS: All IBD patients in eastern Denmark <15 years of
      age diagnosed in the period 1998-2006 starting their first SST within 2 years of
      diagnosis were included. RESULTS: In all, 205 IBD patients were included (105
      Crohn's disease [CD], 100 ulcerative colitis [UC]). Eighty-seven CD (83%) and 77
      (77%) UC patients started SST. In CD, 55 (63%), 25 (29%), and 7 (8%) had a
      complete response (CR), partial response (PR), or no response (NR), respectively,
      30 days after initiation of SST. Fifty (58%) had a prolonged response (PRO) and
      32 (37%) were steroid-dependent (SD). In UC, 49 (64%), 22 (28%), and 6 (8%) had
      CR, PR, and NR, respectively, and 38 (49%) and 38 (49%) were PRO and SD. The
      cumulative risk of surgery 1 year after starting SST was 11.5% and 7.8% for CD
      and UC patients, respectively. After a median follow-up period of 5.1 years, no
      difference in the risk of surgery or periods of activity and remission was found
      between PRO and SD in CD or UC. IM use was associated with a milder disease
      course in UC patients. CONCLUSIONS: No difference in surgery rates or disease
      course was found between SD and PRO. Surgery rates were lower than rates from
      studies predating the era of IM, indicating a putative effect of IM on disease
      course.

PMID- 21744429
TI  - Screening for cervical and breast cancer among women with inflammatory bowel
      disease: a population-based study.
AB  - BACKGROUND: There are limited data on rates and predictors of cervical and/or
      breast cancer screening among women with inflammatory bowel disease (IBD).
      Immunosuppressant medications used to manage IBD may increase the risk of
      cervical cancer precursor lesions. METHODS: Women diagnosed with IBD prior to
      2002 were matched to up to 10 Manitoba residents without the disease. Logistic
      regression analyses were performed to compare utilization of Papanicolaou (Pap)
      tests and mammograms in the two groups. Among women with IBD, we analyzed the
      differences in screening between those with and without exposure to
      immunosuppressant medications and/or corticosteroids and effect of age,
      socioeconomic status, prior diagnostic testing, and intensity of healthcare
      utilization. RESULTS: In all, 54% of the 2344 women with IBD and 52% of the
      15,333 controls had regular Pap tests between 2002 and 2008. In multivariate
      analyses, older age, lower socioeconomic status, lower intensity of healthcare
      utilization, Crohn's disease, and exposure to immunosuppressant medications were
      independent predictors of lower use of Pap testing. Although there were no
      significant differences in the use of mammograms in women with or without IBD or
      among women with IBD with or without exposure to immunosuppressant medications,
      only 47% of women with IBD in the target age group had mammograms regularly.
      CONCLUSIONS: Despite a need for higher testing, women with IBD on
      immunosuppressant medications are less likely to undergo Pap testing. Healthcare
      providers involved in the care of women with IBD need to remind these individuals
      about regular preventive care.

PMID- 21744430
TI  - Fistulizing perianal Crohn's disease: contrast-enhanced magnetic resonance
      imaging assessment at 1 year on maintenance anti-TNF-alpha therapy.
AB  - BACKGROUND: The aim of the study was to assess perianal fistulas by magnetic
      resonance imaging (MRI) in patients with severe fistulizing Crohn's disease (CD)
      using maintenance antitumor necrosis factor alpha (TNF-alpha) therapy and to
      correlate MRI changes with clinical outcome. METHODS: Perineal MRI before and
      after a 1-year scheduled anti-TNF-alpha maintenance therapy was performed in 20
      patients (14 females; mean age = 33.7). The Van Assche score (i.e., number of
      fistulas, localization, and extension, importance of T2 hyperintensity, presence
      of abscess) was calculated. Fistula track contrast enhancement was also used.
      Clinical outcome was defined as no response, response, or remission. RESULTS:
      Response and remission were observed in respectively 40% and 35% of cases. The
      Van Assche score varied from 13.8 (7-20) to 6.13 (0-12) in patients with a
      response or remission (P < 0.05). The T2 hyperintensity follow-up value decreased
      in patients in response or remission (P < 0.01). T2 hyperintensity disappeared or
      decreased in 14 out of 15 patients in clinical response or remission as compared
      to one among the five nonresponding patients (P < 0.01). The decrease in Van
      Assche score and hyperintensity value was not significantly different in patients
      in remission compared to those with response. Only one patient in clinical
      remission had a persisting contrast enhancement on MRI, whereas contrast
      enhancement persisted in all other patients not in remission (P = 0.002).
      CONCLUSIONS: The clinical benefit of maintenance anti-TNF-alpha therapy in
      perianal CD is associated with a significant improvement of the Van Assche score,
      particularly T2 hyperintensity. The disappearance of contrast enhancement was the
      only semiological MR feature associated with remission.

PMID- 21744431
TI  - Magnetic resonance imaging for evaluation of Crohn's disease: validation of
      parameters of severity and quantitative index of activity.
AB  - BACKGROUND: The use of magnetic resonance imaging (MRI) for assessment of Crohn's
      disease (CD) is expanding. The aim of this study is to define and provide an
      external validation of the MRI predictors of active CD, severe CD, and a
      quantitative Magnetic Resonance Index of Activity (MaRIA). METHODS: In all, 48
      patients with clinically active (n = 29) or inactive (n = 19) CD underwent
      ileocolonoscopy (reference standard) and MRI. T2-weighted and pre- and
      postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity
      was evaluated by the Crohn's Disease Endoscopic Index of Severity (CDEIS), and
      also classified as absent, mild (inflammation without ulcers), or severe
      (presence of ulceration). RESULTS: In complete agreement with a previous
      derivation study, independent predictors of disease severity using CDEIS as a
      reference were wall thickness, relative contrast enhancement (RCE), presence of
      edema, and ulcers on MRI. Estimation of activity in each segment using this
      regression model, or another with simplified coefficients (MaRIA(S) = 1.5*wall
      thickness + 0.02*RCE + 5*edema + 10*ulceration) correlated with CDEIS (r = 0.798,
      P< 0.001; r = 0.80 P < 0.001, respectively). In the validation cohort both
      indexes had a high and equal accuracy for diagnosis of active disease: receiver
      operator characteristic (ROC) area 0.93, sensitivity 0.87, specificity 0.87 using
      a cutoff point >= 7, and for diagnosis of severe disease: ROC area 0.96,
      sensitivity 0.92, specificity 0.92 using a cutoff point >= 11. The total of
      segment values (MaRIA(T)) correlated with global CDEIS (r = 0.83, P< 0.001).
      CONCLUSIONS: The MRI variables that should be evaluated in clinical practice to
      diagnose active CD and severe CD are validated, as well as the quantitative index
      of activity for use in research studies.

PMID- 21744432
TI  - Brain functional changes in patients with ulcerative colitis: a functional
      magnetic resonance imaging study on emotional processing.
AB  - BACKGROUND: Ulcerative colitis (UC) is associated with psychological stress and
      poor emotional functioning. The neural emotional processing involves the complex
      integration of several cortical and subcortical brain structures. The amygdala
      plays a fundamental role in the neural processing of emotional stimuli and is a
      core structure of the brain-gut axis (BGA) that represents the anatomo-functional
      substrate for the bidirectional influences between emotions and gastrointestinal
      functions. The aim of this study was to investigate the brain emotional
      processing in UC patients compared to healthy people. METHODS: Ten UC patients in
      remission and 10 matched healthy controls underwent a functional magnetic
      resonance imaging (fMRI) scan while performing a task involving emotional visual
      stimuli. A set of negative, positive, and neutral pictures were used to study
      brain-related emotional responses. RESULTS: A significantly reduced blood oxygen
      level-dependent (BOLD) signal in UC patients relative to controls was found in
      the amygdala, thalamic regions, and cerebellar areas (P < 0.05 corrected for
      multiple comparisons). The group-related differences were detected in the brain
      activity in response to positive emotional stimuli. CONCLUSIONS: UC is associated
      with an emotional dysfunction characterized by decreased sensitivity to emotions
      with a positive content. The previous intestinal inflammatory activity in UC
      patients might have contributed to determine the functional changes of the
      amygdala that we found. On the other hand, the dysfunction of the amygdala may
      influence the course of the disease.

PMID- 21744433
TI  - Incidence trends of pediatric inflammatory bowel disease in Finland, 1987-2003, a
      nationwide study.
AB  - BACKGROUND: The present study aimed to characterize the incidence of pediatric
      inflammatory bowel disease (IBD) in Finland and determine its temporal trends.
      METHODS: The patients' data were based on the database of the Social Insurance
      Institution. New cases diagnosed with IBD at the age <18 years in Finland between
      years 1987-2003 were included. Annual incidence rates were calculated per 100,000
      pediatric populations (with 95% confidence intervals [CI]). The country is
      divided into 21 hospital districts and regional differences were evaluated
      accordingly. RESULTS: The incidence of pediatric IBD increased from 5 per 100,000
      in 1987 to 15 per 100,000 in 2003. The average rate of increase was 6.5% per year
      (95% CI 5.4%-7.5%). The trends were comparable for boys and girls, also by age
      group. Information on disease subtype was available from 1992 and during this 12
      year period the incidence of Crohn's disease (CD) increased from 2-5 per 100,000
      and that of ulcerative colitis (UC) from 4-9 per 100,000. CONCLUSIONS: Our
      results demonstrate a very high incidence rate for childhood IBD and in
      particular UC in Finland. Furthermore, a rapid increase took place nationwide in
      the incidence of both CD and UC during the past two decades.

PMID- 21744434
TI  - Risk of inflammatory bowel disease in first- and second-generation immigrants in
      Sweden: a nationwide follow-up study.
AB  - BACKGROUND: The objective was to analyze whether there is an association between
      country of birth in first-generation immigrants and first hospitalization for an
      inflammatory bowel disease, and to study whether any such association remains in
      second-generation immigrants. METHODS: In this follow-up study a nationwide
      research database at Lund University was used to identify all primary hospital
      diagnoses of Crohn's disease (CD) and ulcerative colitis (UC) in all first- and
      second-generation immigrants in Sweden between January 1, 1964, and December 31,
      2007. Standardized incidence ratios (SIRs) with regard to age, gender, time
      period, geographical region, and socioeconomic status were estimated in first-
      and second-generation immigrants. RESULTS: No increased but some decreased risks
      for CD and UC were found among first-generation immigrants. These decreased risks
      partly remained in the second generation. Moreover, second-generation immigrants
      of Danish, Eastern European, and Iraqi origin had higher risks of CD than the
      reference group. Second-generation immigrants of Finnish and Iranian origin had
      higher risks of UC. CONCLUSIONS: Decreased risks of CD and UC found in some first
      generation immigrant groups partly persisted in the second generation. For some
      immigrant groups, increased risks of CD or UC emerged in the second generation.

PMID- 21744435
TI  - Challenges associated with identifying the environmental determinants of the
      inflammatory bowel diseases.
AB  - In the last several years there has been an explosion in the discovery of
      inflammatory bowel disease (IBD) susceptibility genes; however, similar advances
      in identifying and defining environmental risk factors associated with IBD have
      lagged behind. Moreover, many studies that have explored the same or similar
      environmental risk factors of IBD have demonstrated disparate results and come to
      conflicting conclusions. In order for the field to move forward, it is important
      to understand and resolve why these differences exist. This significant
      heterogeneity has blurred the identification of the fundamental environmental
      determinants of IBD. The purpose of this review article is to explore the factors
      that have likely contributed to the heterogeneity among observational studies of
      environmental risk factors in IBD. In doing so, it is hoped that methodological
      standardization may lead to consistent environmental associations.

PMID- 21744436
TI  - Role of growth factors in the development of lymphangiogenesis driven by
      inflammatory bowel disease: a review.
AB  - Studies on angiogenesis and lymphangiogenesis have gained special relevance in
      research into factors potentially influencing the pathogenesis and course of
      inflammatory bowel disease (IBD). The results of the few existing studies on the
      distribution and density of lymphatic vessels and blood vessels in the context of
      IBD are controversial. Studies using the specific lymphatic marker podoplanin
      have revealed a significantly large number of lymphatic vessels in the colonic
      mucosa of patients with ulcerative colitis and Crohn's disease (compared to
      patients with normal mucosa), whereas other authors have found no significant
      differences. However, the role of vascular endothelial growth factor (VEGF)
      tyrosine-kinase receptor 3 (VEGFR-3) in the onset of IBD has not been analyzed.
      In recent years new biochemical, molecular, and immunohistochemical studies
      indicate that several families of growth factors, such as the VEGF family and
      their receptors, fibroblast growth factor-2, platelet-derived growth factor-BB,
      hepatocyte growth factor, the angiopoietin system, and integrins may play an
      important role in the onset of IBD. To date, no comparative studies have analyzed
      these growth factors and specific lymphatic markers. We examine how growth
      factors are involved in the development of pathological lymphangiogenesis in
      patients with IBD and determine whether they play a crucial role in disease
      exacerbation.

PMID- 21744437
TI  - Does anti-TNF therapy influence the performance of mycobacterium tuberculosis
      antigen-specific interferon-gamma assays? A French multicenter experience.

PMID- 21744438
TI  - Mycobacterium avium subspecies paratuberculosis in children with early-onset
      Crohn's disease: a longitudinal follow-up study.

PMID- 21744439
TI  - Nonmelanoma skin cancers in four IBD patients on treatment with immunosuppressive
      agents.

PMID- 21744440
TI  - First detection of Helicobacter canis in chronic duodenal ulcerations from a
      patient with Crohn's disease.

PMID- 21744441
TI  - Direction of kinetically versus thermodynamically controlled organocatalysis and
      its application in chemoenzymatic synthesis.

PMID- 21744442
TI  - The calcium-chelating capability of tetrahydrofuranic moieties modulates the
      cytotoxicity of annonaceous acetogenins.

PMID- 21744443
TI  - Probing the local environment of Ti3+ ions in TiO2 (rutile) by 17O HYSCORE.
AB  - Reduced states in TiO(2) : (17)O hyperfine sublevel correlation spectroscopy was
      used to monitor the local environment of stable Ti(3+) ions generated in a (17)O
      enriched polycrystalline TiO(2) (rutile) sample. A hyperfine interaction of about
      8 MHz is found, which is analogous to that observed for molecular Ti(3+) aqua
      complex cations and suggests a localized nature of the unpaired electron wave
      function for these centers at 4 K.

PMID- 21744444
TI  - The thermodynamically stable form of solid barbituric acid: the enol tautomer.

PMID- 21744445
TI  - Effect of composition on the catalytic properties of mixed-ligand-coated gold
      nanoparticles.

PMID- 21744446
TI  - Towards direct Mukaiyama-type reactions catalytic in silicon.

PMID- 21744447
TI  - Synthesis of undecachlorosulfolipid A: re-evaluation of the nominal structure.

PMID- 21744448
TI  - Aplysqualenol A binds to the light chain of dynein type 1 (DYNLL1).
AB  - A bidirectional affinity system has been developed for the identification of
      cancer-related natural products and their biological targets. Aplysqualenol A is
      thus selectively identified as a ligand of the dynein light chain. The use of
      forward and reverse affinity methods suggests that both small-molecule isolation
      and target identification can be conducted using conventional molecular
      biological methods.

PMID- 21744449
TI  - Square-planar iridium(II) and iridium(III) amido complexes stabilized by a PNP
      pincer ligand.
AB  - Squaring the circle: the novel dienamido pincer ligand N(CHCHPtBu(2))(2)(-)
      affords the isolation of the unusual square-planar iridium(II) and iridium(III)
      amido complexes [IrCl{N(CHCHPtBu(2))(2)}](n) (n=0 (1), +1 (2)). In contrast, the
      corresponding iridium(I) complex of the redox series (n=-1) is surprisingly
      unstable. The diamagnetism of 2 is attributed to strong N->Ir pi donation.

PMID- 21744450
TI  - Artificial molecular clamp: a novel device for synthetic polymerases.

PMID- 21744451
TI  - Palladium-catalyzed selective dehydrogenative cross-couplings of heteroarenes.

PMID- 21744452
TI  - Total chemical synthesis of biologically active vascular endothelial growth
      factor.
AB  - Efficient access: the 204-residue covalent-dimer vascular endothelial growth
      factor with full mitogenic activity was prepared from three unprotected peptide
      segments by one-pot native chemical ligations. The covalent structure of the
      synthetic VEGF was confirmed by precise mass measurement, and the three
      dimensional structure of the synthetic protein was determined by high-resolution
      X-ray crystallography.

PMID- 21744453
TI  - Double single-crystal-to-single-crystal transformation and small-molecule
      activation in rhodium NHC complexes.
AB  - Three gases, one crystal: rhodium NHC complexes undergo back-to-back single
      crystal-to-single-crystal transformations by selective nonreversible ligand
      exchange reactions. Slow diffusion of O(2) converts a dinitrogen complex into a
      dioxygen complex, and CO subsequently replaces O(2).

PMID- 21744456
TI  - The frataxin homologue Fra plays a key role in intracellular iron channeling in
      Bacillus subtilis.
AB  - Frataxin homologues are important iron chaperones in eukarya and prokarya. Using
      a native proteomics approach we were able to identify the structural frataxin
      homologue Fra (formerly YdhG) of Bacillus subtilis and to quantify its native
      iron-binding stoichiometry. Using recombinant proteins we could show in vitro
      that Fra is able to transfer iron onto the B. subtilis SUF system for iron-sulfur
      cluster biosynthesis. In a four-constituents reconstitution system (including
      SufU, SufS, Fra and CitB) we observed a Fra-dependent formation of a [4 Fe-4 S]
      cluster on SufU that could be efficiently transferred onto the target apo
      aconitase (CitB). A Deltafra deletion mutant showed a severe growth phenotype
      associated with a broadly disturbed iron homeostasis; this indicates that Fra is
      a central component of intracellular iron channeling in B. subtilis.

PMID- 21744457
TI  - Structural basis of Bcl-xL recognition by a BH3-mimetic alpha/beta-peptide
      generated by sequence-based design.
AB  - The crystal structure of a complex between the prosurvival protein Bcl-x(L)  and
      an alpha/beta-peptide 21-mer is described. The alpha/beta-peptide contains six
      beta-amino acid residues distributed periodically throughout the sequence and
      adopts an alpha-helix-like conformation that mimics the bioactive shape of the
      Puma BH3 domain. The alpha/beta-peptide forms all of the noncovalent contacts
      that have previously been identified as necessary for recognition of the
      prosurvival protein by an authentic BH3 domain. Comparison of our alpha/beta
      peptide:Bcl-x(L)  structure with structures of complexes between native BH3
      domains and Bcl-2 family proteins reveals how subtle adjustments, including
      variations in helix radius and helix bowing, allow the alpha/beta-peptide to
      engage Bcl-x(L)  with high affinity. Geometric comparisons of the BH3-mimetic
      alpha/beta-peptide with alpha/beta-peptides in helix-bundle assemblies provide
      insight on the conformational plasticity of backbones that contain combinations
      of alpha- and beta-amino acid residues. The BH3-mimetic alpha/beta-peptide
      displays prosurvival protein-binding preferences distinct from those of Puma BH3
      itself, even though these two oligomers have identical side-chain sequences. Our
      results suggest origins for this backbone-dependent change in selectivity.

PMID- 21744458
TI  - Ferromagnetism exhibited by nanoparticles of noble metals.
AB  - Gold nanoparticles with average diameters in the range 2.5-15 nm, prepared at the
      organic/aqueous interface by using tetrakis(hydroxymethyl)phosphonium chloride
      (THPC) as reducing agent, exhibit ferromagnetism whereby the saturation
      magnetization M(S) increases with decreasing diameter and varies linearly with
      the fraction of surface atoms. The value of M(S) is higher when the particles are
      present as a film instead of as a sol. Capping with strongly interacting ligands
      such as alkane thiols results in a higher M(S) value, which varies with the
      strength of the metal-sulfur bond. Ferromagnetism is also found in Pt and Ag
      nanoparticles prepared as sols, and the M(S) values vary as Pt>Au>Ag. A careful
      study of the temperature variation of the magnetization of Au nanoparticles,
      along with certain other observations, suggests that small bare nanoparticles of
      noble metals could indeed possess ferromagnetism, albeit weak, which is
      accentuated in the presence of capping agents, specially alkane thiols which form
      strong metal-sulfur bonds.

PMID- 21744459
TI  - Nanoscale effects on thermodynamics and phase equilibria in oxide systems.
AB  - Because different solid materials (phases) have different surface energies,
      equilibria among them will be significantly affected by particle size. This
      Minireview summarizes experimental (calorimetric) data for the surface energies
      of oxides and discusses shifts in the stability of polymorphs, the thermodynamics
      of hydration, and oxidation-reduction reactions in nanoscale oxide systems.

PMID- 21744460
TI  - Prediction of a new delocalised bonding motif between group 15 or group 16 atoms.

PMID- 21744463
TI  - Predictors of associated autoimmune diseases in families with type 1 diabetes:
      results from the Type 1 Diabetes Genetics Consortium.
AB  - BACKGROUND: Type 1 diabetes (T1D) is a clinically heterogeneous disease. The
      presence of associated autoimmune diseases (AAIDs) may represent a distinct form
      of autoimmune diabetes, with involvement of specific mechanisms. The aim of this
      study was to find predictors of AAIDs in the Type 1 Diabetes Genetics Consortium
      data set. METHODS: Three thousand two hundred and sixty-three families with at
      least two siblings with T1D were included. Clinical information was obtained
      using questionnaires, anti-GAD (glutamic acid decarboxylase) and anti-protein
      tyrosine phosphatase (IA-2) were measured and human leukocyte antigen (HLA)
      genotyping was performed. Siblings with T1D with and without AAIDs were compared
      and a multivariate regression analysis was performed to find predictors of AAIDs.
      T1D-associated HLA haplotypes were defined as the four most susceptible and
      protective, respectively. RESULTS: One or more AAIDs were present in 14.4% of the
      T1D affected siblings. Age of diabetes onset, current age and time since
      diagnosis were higher, there was a female predominance and more family history of
      AAIDs in the group with AAIDs, as well as more frequent anti-GAD and less
      frequent anti-IA-2 antibodies. Risk and protective HLA haplotype distributions
      were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group
      with AAIDs. In the multivariate analysis, female gender, age of onset, family
      history of AAID, time since diagnosis and anti-GAD positivity were significantly
      associated with AAIDs. CONCLUSIONS: In patients with T1D, the presence of AAIDs
      is associated with female predominance, more frequent family history of AAIDs,
      later onset of T1D and more anti-GAD antibodies, despite longer duration of the
      disease. The predominance of certain HLA haplotypes suggests that specific
      mechanisms of disease may be involved.

PMID- 21744464
TI  - Highly sensitive spectrofluorimetic determination of rutin based on its activated
      effect on a multi-enzyme redox system.
AB  - A highly sensitive and simple spectrofluorimetric method for the determination of
      rutin, based on its activated effect on a haemoglobin-catalysed reaction, was
      developed. Under optimum conditions, the concentration of rutin was linear, with
      decreased fluorescence (DeltaF) of the system under optimal experimental
      conditions. The calibration graph was linear in the range 1.0 * 10(-7) -3.0 * 10(
      5)  mol/L, with a detection limit of 7.0 * 10(-8)  mol/L. The relative standard
      deviation (RSD) was 3.26% for 11 determinations of 1.0 * 10(-5)  mol/L. This
      method was used for the determination of rutin in pharmaceuticals with
      satisfactory results.

PMID- 21744465
TI  - Determination of 5-hydroxytryptamine in serum by electrochemiluminescence
      detection with the aid of capillary electrophoresis.
AB  - A rapid, sensitive and simple electrochemiluminescence method for the
      determination of 5-hydroxytryptamine (5-HT) using capillary electrophoresis was
      proposed. The experimental parameters, including the detection potential, the
      concentration of Ru(bpy)(3)(2+), the concentration and pH of phosphate buffer for
      separation and detection, the injection voltage and time and the separation
      voltage on the determination of 5-HT, were optimized. Under the optimized
      conditions, the linear concentration range for 5-HT was 3.5 * 10(-9) -5.1 * 10(
      3) mol/L, with a detection limit of 5 * 10(-10) mol/L. The relative standard
      deviations (RSDs) of the ECL intensity and the migration times for six continuous
      injections of 1.0 umol/L 5-HT were 2.48% and 1.3%, respectively. The method was
      successfully applied to 5-HT assay in samples of human serum in 5 min and the
      extraction recoveries with spiked serum samples were over 94.4%.

PMID- 21744466
TI  - Substance use by liver transplant candidates: an anonymous urinalysis study.
AB  - Toxicological urinalysis is a highly sensitive and specific test that detects
      recent substance use. It has been established for substance misuse treatment but
      has not been routinely used at liver transplantation (LT) centers. Patients with
      a history of substance misuse are required to be abstinent from alcohol and
      illicit drugs before they are listed for LT. In this cross-sectional study, we
      sought to determine the prevalence of recent substance use in LT candidates via
      toxicological urinalysis. One hundred nine adults who were admitted for an LT
      assessment provided data, and they were categorized by the etiology of their
      liver disease [alcohol-related liver disease (ALD), hepatitis C virus (HCV), or
      other liver diseases]. Urine was toxicologically screened for drugs and their
      metabolites as well as the urinary alcohol metabolites ethyl glucuronide and
      ethyl sulfate. The prevalence of alcohol metabolites in patients with ALD was
      20%. Licit and illicit substances together provided a positive toxicological
      result in 30% of the patients. Positive results were more common among patients
      with HCV (40%) and ALD (38%) versus patients with other liver diseases (18%).
      During the clinical assessment, 4% of the patients with ALD or HCV self-reported
      current alcohol or illicit drug use. These results correspond to the findings of
      other studies and emphasize the uncertainty of self-reported substance use data
      for LT candidates.

PMID- 21744467
TI  - Portal vein thrombosis and outcomes for pediatric liver transplant candidates and
      recipients in the United States.
AB  - The effect of occlusive portal vein thrombosis (PVT) on the mortality of
      pediatric liver transplant candidates and recipients is poorly defined. Using
      standard multivariate techniques, we studied the relationship between PVT and
      waiting-list and posttransplant survival rates with data from the Scientific
      Registry of Transplant Recipients (September 2001 to December 2007). In all, 5087
      liver transplant candidates and 3630 liver transplant recipients were evaluated
      during the period. PVT was found in 1.4% of the liver transplant candidates (n =
      70) and in 3.7% of the liver transplant recipients (n = 136). PVT was not
      associated with increased wait-list mortality [hazard ratio (HR) = 1.1, 95%
      confidence interval (CI) = 0.5-2.4, P = 0.77]. Conversely, PVT patients had a
      significantly lower unadjusted survival rate in the posttransplant period (P =
      0.01). PVT was independently associated with increased posttransplant mortality
      in multivariate models (30-day survival: HR = 2.9, 95% CI = 1.6-5.3, P = 0.001;
      overall survival: HR = 1.7, 95% CI = 1.1-2.4, P = 0.01). The presence of PVT in
      pediatric liver candidates was not associated with increased wait-list mortality
      but was clearly associated with posttransplant mortality, especially in the
      immediate postoperative period.

PMID- 21744468
TI  - Impact of reversible cardiac arrest in the brain-dead organ donor on the outcome
      of adult liver transplantation.
AB  - Several donor and graft characteristics are associated with higher failure rates
      for deceased donor liver transplantation (LT). The influence of reversible
      cardiac arrest in the donor on these failure rates is unclear because of scarce
      and inconsistent data. The aim of this study was to determine whether reversible
      cardiac arrest in the donor could affect the early postoperative outcome of LT.
      From January 2008 to February 2010, 165 patients underwent LT, and they were
      retrospectively divided into 2 groups: a cardiac arrest group (34 patients who
      received grafts from donors who had experienced reversible cardiac arrest before
      organ procurement) and a control group (131 patients who received grafts from
      donors without a history of reversible cardiac arrest). The postoperative
      complications and the graft and recipient outcomes were prospectively recorded
      for all the patients. Graft failure was defined as death or the need for
      retransplantation within 90 days of LT. Donors in the cardiac arrest group
      displayed higher serum aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) levels than donors in the control group [AST: 104 (19-756)
      versus 42 IU/L (10-225 IU/L), P < 0.001; ALT: 73 (13-869) versus 29 IU/L (6-549
      IU/L), P < 0.001]. However, no difference in the graft failure rates was found
      between the 2 groups (11.8% versus 8.4%, P = 0.51). The biological parameters 5
      and 7 days after LT and the peak AST/ALT levels were similar for the 2 groups.
      Furthermore, the 2 groups had similar graft and patient survival rates at the 6
      month mark (87% and 88%, respectively). In conclusion, our study shows that brief
      and reversible cardiac arrest in organ donors does not affect post-LT allograft
      survival and function, even though liver function test values are higher for
      these donors. However, the risk of using these grafts needs to be balanced
      against the potential benefits for the recipients.

PMID- 21744469
TI  - Impact of the duration of posttransplant renal replacement therapy on bacterial
      infections in liver transplant recipients.
AB  - Whether the duration of renal replacement therapy (RRT) after liver
      transplantation influences the rate and types of bacterial infections is not
      known. In this study, 47 of 299 consecutive liver transplant recipients (16%)
      required posttransplant RRT. The incidence of bacterial infections was higher in
      the RRT group versus the non-RRT group (8.84 versus 1.38 per 1000 patient days, P
      < 0.001). In the RRT group, 49% of the patients (23/47) required long-term RRT
      (>=30 days), and 51% (24/47) required short-term RRT (<30 days). Long-term RRT
      (hazard ratio = 2.27, 95% confidence interval = 1.16-4.47, P = 0.017) was a
      significant predictor of infections. Bacteremia and intra-abdominal infections
      were the most common sources of infections, and Enterobacteriaceae and
      enterococci were the predominant pathogens in both groups. The mortality rate for
      patients requiring RRT was higher than the rate for patients not requiring RRT (P
      < 0.001), but the mortality rates of the short-term RRT group and the long-term
      RRT group did not significantly differ (P = 0.654). In conclusion, although both
      short-term RRT and long-term RRT confer a higher risk of bacterial infections,
      only long-term RRT is a statistically significant predictor of these infections.

PMID- 21744470
TI  - Is tumor biopsy necessary?

PMID- 21744471
TI  - Rhabdoid tumors of the liver: rare, aggressive, and poorly responsive to standard
      cytotoxic chemotherapy.
AB  - BACKGROUND: Rhabdoid tumors of the liver are rare tumors that are difficult to
      cure. We compiled all the cases previously reported in the literature to review
      clinical data, treatments, and outcomes. PROCEDURE: Patients were identified by
      literature review using PubMed. RESULTS: Thirty-four patients were identified.
      The median age at presentation was 8 months. All patients with reported AFP
      results exhibited normal or minimally increased serum AFP levels. All 10 tumors
      with reported INI1 immunohistochemistry results were reported as negative. Twenty
      one patients presented with metastatic disease at diagnosis. Thirty patients died
      of disease or treatment complications. Most deaths occurred within 12 months
      after diagnosis. Five patients survived at the time of the reports with one
      patient alive with disease. One patient relapsed and subsequently died after the
      report was published. Of the four patients alive without disease, all were
      treated with chemotherapy, and at least three had surgery or transplantation. Two
      patients received radiation therapy but did not survive. CONCLUSIONS: Rhabdoid
      tumors of the liver are aggressive, rare tumors of the infant liver that are
      often associated with metastases at the time of diagnosis. Mortality is high and
      often occurs soon after diagnosis. Treatment with aggressive chemotherapy in
      combination (especially an alkylating agents doxorubicin) with complete resection
      may lead to improved outcomes. Therapy targeted to the INI1 mutation of these
      tumors is currently being investigated and may offer greater hope of cure.

PMID- 21744472
TI  - External-beam radiotherapy for pediatric and young adult desmoid tumors.
AB  - BACKGROUND: To report long-term outcomes following radiotherapy for desmoid
      tumors in children and young adults and identify variables impacting local
      regional control and treatment complications. PROCEDURE: From 1978 to 2008, 30
      patients <30 years old were treated with radiotherapy for a pathologically
      confirmed desmoid tumor. The median age at radiotherapy was 23.7 years old
      (range, 10.3-29.9). Fifteen patients underwent definitive radiotherapy, 14
      received radiotherapy after gross total resection, and 1 received preoperative
      radiotherapy. Sixteen patients received 1.8 Gy once daily and 14 received 1.2 Gy
      twice daily. Variables analyzed for prognostic value included gender, age at
      diagnosis, primary or recurrent presentation, age at radiotherapy, tumor site,
      tumor size, extent of resection, fractionation schedule, and radiotherapy dose.
      RESULTS: The actuarial 15-year overall survival and local-regional control rates
      were 96% and 55%, respectively. Local-regional control in patients <18 years old
      at the time of radiotherapy was 20% versus 63% in those 18-30 years old (P =
      0.08). Local-regional control rates for tumors receiving >= 55 Gy and < 55 Gy
      were 79% and 30%, respectively (P = 0.02). No other factors had a statistically
      significant association with local-regional control by univariate analysis.
      Twelve of 30 patients experienced grade 3-4 complications, including pathologic
      fractures, impaired range of motion, pain, and in-field skin cancers.
      CONCLUSIONS: The role of radiotherapy in managing young patients with desmoid
      tumors remains unclear. Younger patient age is associated with inferior local
      regional control following RT. In children and young adults, doses >=55 Gy were
      associated with improved tumor control, but also lead to increased risk of
      complications.

PMID- 21744473
TI  - Initial testing of the hypoxia-activated prodrug PR-104 by the pediatric
      preclinical testing program.
AB  - BACKGROUND: PR-104 is rapidly hydrolyzed to PR-104A in vivo, which is activated
      by reduction to the corresponding 5-hydroxylamine (PR-104H) and amine (PR-104M)
      to produce DNA interstrand cross-links. PR-104 activation can occur via hypoxia
      dependent reductases and also independently of hypoxia by aldo-keto reductase
      (AKR) 1C3. PROCEDURES: PR-104A was tested against the PPTP in vitro panel (10 nM
      to 100 uM), and PR-104 in vivo using a weekly * 6 schedule at its maximum
      tolerated dose (MTD) of 550 mg/kg. Subsequently PR-104 was tested at 270 and 110
      mg/kg. Pharmacokinetics for PR-104 and its metabolites were determined, as were
      levels of AKR1C3 RNA and protein in xenografts. RESULTS: In vitro, the leukemia
      models were most sensitive to PR-104A. In vivo, PR-104 induced objective
      responses at its MTD in 21/34 solid tumor models and maintained complete
      responses against 7/7 acute lymphoblastic leukemia (ALL) models. At 270 mg/kg and
      lower dose levels, PR-104 did not induce solid tumor regressions, suggesting a
      steep dose-response relationship. Pharmacokinetic analysis suggests higher
      systemic exposures to PR-104A and its metabolites in mice compared to those
      achievable in patients. Levels of AKR1C3 protein did not correlate with tumor
      responsiveness. CONCLUSIONS: As monotherapy, PR-104 demonstrated a high level of
      activity against both solid tumor and ALL models at its MTD, but the activity was
      almost completely lost at half the MTD dose for solid tumors. Pharmacokinetic
      data at the PR-104 MTD from human trials suggest that PR-104 metabolites may not
      reach the plasma exposures in children that were associated with high-level
      preclinical activity.

PMID- 21744474
TI  - Phase I study of tandem high-dose chemotherapy with autologous peripheral blood
      stem cell rescue for children with recurrent brain tumors: a Pediatric Blood and
      MarrowTransplant Consortium study.
AB  - BACKGROUND: High-dose chemotherapy with autologous stem cell rescue (HDC/SCR) has
      produced responses and prolonged survival for some children with recurrent brain
      tumors, but is associated with considerable morbidity and mortality. A Phase I
      trial of two cycles of HDC/SCR for recurrent brain tumors in children was
      performed to determine the maximum tolerated doses for a novel regimen.
      PROCEDURES: Two cycles of HDC/SCR were given. Cycle 1 included thiotepa and
      carmustine given on days -5, -4, and -3. Four to six weeks later, patients
      received cycle 2 which included thiotepa and carboplatin given on days -5, -4,
      and -3. Autologous peripheral blood stem cells (PBSC) were infused on day 0 of
      each cycle. RESULTS: Thirty-two patients were treated and 25 patients received
      both cycles of HDC/SCR. Common toxicities included mucositis, emesis, diarrhea,
      anorexia, and pancytopenia. Eight of 32 (25%) assessable children died from
      regimen-related toxicity. Pulmonary failure occurred in seven patients. Seven
      patients had grade 3-4 neurotoxicity. The 3-year event-free survival (EFS) was
      25%. CONCLUSIONS: We determined the maximum tolerated regimen to be thiotepa 600
      mg/m(2) and carmustine 300 mg/m(2) followed by thiotepa 600 mg/m(2) and
      carboplatin 1,200 mg/m(2) . Pulmonary toxicity was considerable. The toxic death
      rate was similar to other trials of HDC/SCR for children with recurrent brain
      tumors performed during the same time period. The regimen resulted in prolonged
      time to progression for a significant number of patients and long-term survival
      for some patients with recurrent medulloblastoma and rhabdoid tumor.

PMID- 21744475
TI  - Use of sentinel node biopsy for staging parameningeal rhabdomyosarcoma.
AB  - Identification of nodal involvement is important for treatment planning in
      patients with rhabdomyosarcoma, and is facilitated by sentinel node biopsy.
      Although it is employed primarily for extremity tumors, we report using sentinel
      node biopsy in a patient with parameningeal rhabdomyosarcoma arising in the
      ethmoid sinus. Lymphoscintigraphy with single photon emission computed tomography
      following injection of tracer at the tumor site helped identify contralateral
      cervical node involvement not previously recognized by physical exam, cross
      sectional imaging, or other functional imaging. This case demonstrates how
      information from sentinel node identification and biopsy can change therapy
      recommendations in patients with parameningeal rhabdomyosarcoma.

PMID- 21744476
TI  - Gastric adenocarcinoma in children and adolescents.
AB  - Gastric adenocarcinoma (GAC) is an extremely rare cancer in children with very
      limited information on the clinical presentation and outcome. We report five
      pediatric patients with GAC-treated between 1990 and 2008 at our institution.
      Median age at diagnosis was 17 years (range: 8-17). Our case series suggests that
      pediatric GAC patients present with diffuse metastatic disease (four patients)
      and with patterns of spread similar to adult GAC. Initial chemotherapy was mainly
      platinum-based. Median time to progression was 4 months. The only long-term
      survivor was a patient with localized disease who had complete surgical removal
      of primary tumor.

PMID- 21744477
TI  - Comparison of permanent hair loss in children with standard risk PNETS of the
      posterior fossa following radiotherapy alone or chemotherapy and radiotherapy
      after surgical resection.
AB  - Hair loss was compared between surgery followed by craniospinal radiotherapy
      (CSRT) or chemotherapy then CSRT (C-CSRT) for medulloblastoma. The proportion of
      patients exhibiting hair loss in the cranial field was 70.0% (C-CSRT) versus
      30.0% (CSRT) (95% CI: 14.7% to 58.9%; P = 0.002). The C-CSRT group also
      experienced more virtual/complete hair loss over the posterior fossa boost. Age
      was a significant contributor to hair loss in the cranial field. Persistent
      significant hair loss is an under-reported late effect of treatment that could
      influence quality of survival and should be considered in future trial design.

PMID- 21744478
TI  - The long road to immunotherapy for childhood rhabdomyosarcoma.

PMID- 21744479
TI  - Notch pathway activation induces neuroblastoma tumor cell growth arrest.
AB  - BACKGROUND: Notch pathway signaling has critical roles in differentiation,
      proliferation, and survival, and has oncogenic or tumor suppressor effects in a
      variety of malignancies. The goal of this study was to evaluate the effects of
      Notch activation on human neuroblastoma cells. PROCEDURE: Quantitative RT-PCR,
      immunoblots, and immunohistochemistry were used to determine the expression of
      Notch receptors (Notch1-4), cleaved Notch1 (ICN1), and downstream targets (HES1
      5) in human neuroblastoma cell lines and patient tumor samples. Notch pathway
      signaling was induced using intracellular Notch (ICN1-3) and HES gene constructs
      or direct culture on Notch ligands. Quantitative methylation-specific PCR was
      used to quantify methylation of the HES gene promoters, and the effects of
      treatment with decitabine were measured. RESULTS: Neuroblastoma cells express
      varying levels of Notch receptors and low levels of HES genes at baseline.
      However, no endogenous activation of the Notch pathway was detected in
      neuroblastoma cell lines or patient tumor samples. Expression of activated Notch
      intracellular domains and HES gene products led to growth arrest. The HES2 and
      HES5 gene promoters were found to be heavily methylated in most neuroblastoma
      lines, and HES gene expression could be induced through treatment with
      decitabine. CONCLUSIONS: We report that neuroblastoma cell lines express multiple
      Notch receptors, which are inactive at baseline. Activation of the Notch pathway
      via ligand binding consistently resulted in growth arrest. HES gene expression
      appears to be regulated epigenetically and could be induced with decitabine.
      These findings support a tumor suppressor role for Notch signaling in
      neuroblastoma.

PMID- 21744480
TI  - Congenital blastic plasmacytoid dendritic cell neoplasm.

PMID- 21744481
TI  - A dose-intensive approach (NB96) for induction therapy utilizing sequential high
      dose chemotherapy and stem cell rescue in high-risk neuroblastoma in children
      over 1 year of age.
AB  - BACKGROUND: To improve outcome and overall survival (OS) in high-risk
      neuroblastoma, NB96 induction therapy was intensified using sequential high-dose
      chemotherapy and autologous stem cell rescue. PROCEDURE: Twenty children were
      included in this pilot study undertaken at seven reference centers in France,
      between May 1995 and October 1996. Induction began with one cycle of conventional
      chemotherapy followed by six sequential cycles of high-dose chemotherapy
      comprising two cycles of etoposide 800 mg/m(2)/day over 3 days, two cycles of
      cyclophosphamide 2,000 mg/m(2)/day over 3 days, and two cycles of carboplatin 400
      mg/m(2)/day over 5 days, followed by stem cell rescue. RESULTS: Thirteen patients
      (13/20) received this induction with acceptable toxicity and adequate stem cell
      harvest. Of these, nine (9/13) underwent surgery according to the protocol, while
      one patient was given a consolidation regimen prior to surgery. No toxic death
      was recorded. At the end of induction, complete remission was achieved in 10
      cases (50%), with six still alive in July 2009. The 5-year event-free survival
      and OS were 35 +/- 11% and 40 +/- 11%, respectively. CONCLUSION: NB96 therapy is
      feasible and tolerated without lethal toxicity. Nevertheless, given the small
      sample size and absence of randomization in our study, the effectiveness of this
      strategy based on metastasis complete response rates and long-term outcome was
      not superior to other intensive chemotherapy regimens.

PMID- 21744482
TI  - Oncologic outcomes of partial versus radical nephrectomy for unilateral Wilms
      tumor.
AB  - BACKGROUND: Radical nephrectomy (RN) is the recommended surgical management as
      part of multi-modality therapy for unilateral Wilms tumor (UWT). Based on recent
      data demonstrating that renal preserving surgery decreases the likelihood of
      chronic renal disease and associated co-morbidities, we analyzed oncologic
      outcomes of patients after partial nephrectomy (PN) for UWT. METHODS: We
      identified all published cases of PN for UWT. Cases of elective PN for UWT were
      analyzed for tumor stage, presence, timing and location of disease recurrence,
      and overall survival (OS). Eighty-two patients had adequate data for analysis.
      For comparison, these endpoints were collected on consecutive children undergoing
      RN for UWT from 1985 to 2010 at our institution. RESULTS: Of the 82 PN patients,
      tumor stage was: I-64, II-10, III-6, IV-2. Of the 121 RN patients, the staging
      was: I-24, II-45, III-29, IV-23. In the PN group, at a median of 48 months (3
      372), the recurrence-free survival (RFS), local RFS and OS were 89.1%, 92.7%, and
      95.1%, respectively. In the RN group, at a median of 69 months (0-214), the RFS,
      local RFS, and OS were 83.1%, 95.0%, and 95.0%, respectively. After controlling
      for stage, there were no statistically significant differences in the above
      oncologic outcomes between the groups. CONCLUSION: Based on reported data, the
      oncologic outcomes of PN for UWT in selected patients do not appear to differ
      from those of RN. PN for appropriately selected patients with UWT should be
      studied in prospective, co-operative group trials.

PMID- 21744483
TI  - Antiangiogenic treatment as a pre-operative management of alveolar soft-part
      sarcoma.
AB  - Alveolar soft-part sarcoma (ASPS) is a rare tumor. Cure is based solely on
      radical surgery. The general prognosis is poor. The tongue is an unusual site in
      adults, but not in children. Tumor removal can cause a severe impact on quality
      of life, even if reconstruction is possible. ASPS is a highly vascularized tumor
      and antiangiogenic therapy may have a role. We describe the use of the
      antiangiogenic combination bevacizumab and celecoxib in the preoperative
      management of a patient with an ASPS of the tongue.

PMID- 21744484
TI  - Childhood cancer survivorship educational resources in North American
      hematology/oncology fellowship training programs: a survey study.

PMID- 21744486
TI  - Wolf-Hirschhorn syndrome due to pure and translocation forms of monosomy 4p16.1 
      > pter.
AB  - The aim of this study was to obtain a quantitative definition of Wolf-Hirschhorn
      syndrome (WHS) through systematic phenotypic analyses in a group of six children
      with 4p15.32 -> pter, 4p15.33 -> pter, or 4p16.1 -> pter monosomy (considered
      together as M4p16.1). These results were used for evaluation of the phenotypic
      effects of a double chromosome imbalance in one child with 4p16.1 -> pter
      monosomy and additional 11q23.3 -> qter trisomy. Children with pure M4p16.1
      presented with a total of 227 clinical and morphological traits, of which 119
      were positive in at least two of them. These traits overlap to a great extent
      with clinical criteria defining the WHS phenotype. Among the 103 traits
      identified in the child with unbalanced translocation der(4)t(4;11)(p16.1;q23.3),
      most clinical and developmental traits (but only 11 morphological) were found to
      be shared by WHS children with pure M4p16.1 and at least one reported patient
      with pure 11q trisomy. Forty-six traits of this child corresponded solely to
      those identified in at least one child with pure M4p16.1. Only five traits of the
      hybrid phenotype were present in at least one child with pure distal 11q trisomy
      but in none of the present children with pure M4p16.1. In conclusion, most of the
      morphological traits of the hybrid phenotype in the child with
      der(4)t(4;11)(p16.1;q23.3) can be attributed to the M4p16.1, whereas their
      overlap with those associated with pure distal 11q trisomy is less evident.
      Phenotype analyses based on the same systematic data acquisition may be useful in
      understanding the phenotypic effects of different chromosome regions in complex
      rearrangements. (c) 2011 Wiley-Liss, Inc.

PMID- 21744485
TI  - Massive accidental overdose of hydroxyurea in a young child with sickle cell
      anemia.
AB  - The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) confirmed safety
      and efficacy of hydroxyurea therapy for infants with sickle cell anemia.
      Treatment was associated with reduction in rates of pain, acute chest syndrome,
      hospitalizations, and blood transfusions; improved hematologic values; and,
      perhaps, preservation of organ function. During the study, a 2-year-old ingested
      at one time an entire 35-day supply of hydroxyurea (612 mg/kg body weight).
      Despite a serum level of 7,756 uM 4 hours post-ingestion, the only toxicity was
      transient mild myelosuppression. With wider usage of hydroxyurea anticipated,
      conservative management of future overdoses seems reasonable (ClinicalTrials.gov
      NCT00006400).

PMID- 21744487
TI  - Expanding the clinical and neuroradiological phenotype of 6q27 microdeletion:
      olfactory bulb aplasia and anosmia.
AB  - Subtelomeric deletions of chromosome 6q may result in a syndrome with brain
      malformations, comprising hydrocephalus and hypoplasia of the corpus callosum.
      Aplasia of the olfactory bulbs (OB) or anosmia has not been described in this
      syndrome. We describe a 3-year-old girl and a 25-year-old man with subtelomere 6q
      deletions. Both patients had aplastic OB and hydrocephalus. Subtelomeric 6q
      deletions might be underdiagnosed as anosmia can be the only symptom.

PMID- 21744488
TI  - The proximal chromosome 14q microdeletion syndrome: delineation of the phenotype
      using high resolution SNP oligonucleotide microarray analysis (SOMA) and review
      of the literature.
AB  - We report on two patients with overlapping small interstitial deletions involving
      regions 14q12 to 14q13.1. Both children had severe developmental delay, failure
      to thrive, microcephaly, and distinctive facial features, including abnormal
      spacing of the eyes, epicanthal folds, sloping forehead, low-set ears, rounded
      eyebrows with triangular media aspect and outer tapering, depressed and broad
      nasal bridge, small mouth, a long philtrum, and a prominent Cupid's bow. Brain
      MRI of both children showed partial agenesis of the corpus callosum. Our first
      patient had bilateral hypoplastic optic nerves causing blindness, mild hearing
      impairment, sinus arrhythmia, abnormal temperature regulation, frequent apneic
      episodes, myoclonic jerks, and opisthotonus. Our second patient had a seizure
      disorder confirmed by EEG, sleep apnea, chronic interstitial lung disease, and
      several episodes of pneumonia and gastroenteritis. Cytogenetic analysis showed a
      normal karyotype in Patient 1 and a unique apparently balanced three-way
      translocation in Patient 2 involving chromosomes 4, 14, and 11. High resolution
      SNP Oligonucleotide Microarray Analysis (SOMA) revealed a deletion in the
      proximal region of chromosome 14q overlapping with the deletion of our first
      patient, and no copy number changes in chromosomes 4 and 11. Here, we review and
      compare published cases with a deletion involving the 14q12-22.1 chromosomal
      region in an effort to correlate phenotype and genotype. We also examine the
      underlying genomic architecture to identify the possible mechanism of the
      chromosomal abnormality. Our review found a patient with a mirror duplication of
      our first patient's deletion, confirming the existence of an underlying genomic
      structural instability in the region. (c) 2011 Wiley-Liss, Inc.

PMID- 21744489
TI  - Masticatory muscle defects in hemifacial microsomia: a new embryological concept.
AB  - First arch syndromes correspond to a wide spectrum of human latero-facial
      congenital anomalies affecting cranial neural crest cells (CNCCs) derivatives of
      the first pharyngeal arch (PA1). The abnormal traits display variable
      quantitative expression and are often unilateral. Mandibular skeletal defects are
      invariably accompanied by hypoplasia or agenesis of masticatory muscles, but no
      explanation has been proposed for this association. Indeed, during embryonic
      development, CNCCs give only rise to skeletal components of the head while
      muscles derive from cephalic myogenic mesodermal cells (CMMCs). Recent studies on
      animal models have shown that communication between CNCCs and CMMCs is essential
      for the development of masticatory muscles: genetic lesions affecting only CNCCs
      can prevent muscularization of the jaws. To evaluate the involvement of CNCC/CMMC
      interactions in human craniofacial development, we performed a quantitative
      analysis of masticatory muscle and mandibular bone volumes on craniofacial CT
      scans from 8 children, ages 3 months to 16 years, affected by hemifacial
      microsomia. We found that: (1) in seven patients the masseter muscle is absent in
      the affected side; (2) the absence of masseter is correlated neither with the age
      of the patients nor with the volume and shape of the affected ramus; and (3) in
      all cases the pterygoid and the temporal muscles are either reduced or absent.
      Our findings suggest that an early developmental event is the origin of the
      muscular defects in these patients. We propose that the hypoplasia or agenesis of
      masticatory muscles derives from a defect in the CNCCs/CMMCs communication during
      early embryonic development.

PMID- 21744490
TI  - Deletions and duplications of developmental pathway genes in 5q31 contribute to
      abnormal phenotypes.
AB  - Although copy number changes of 5q31 have been rarely reported, deletions have
      been associated with some common characteristics, such as short stature, failure
      to thrive, developmental delay (DD)/intellectual disability (ID), club feet,
      dislocated hips, and dysmorphic features. We report on three individuals with
      deletions and two individuals with duplications at 5q31, ranging from 3.6 Mb to
      8.1 Mb and 830 kb to 3.4 Mb in size, respectively. All five copy number changes
      are apparently de novo and involve several genes that are important in
      developmental pathways, including PITX1, SMAD5, and WNT8A. The individuals with
      deletions have characteristic features including DD, short stature, club feet,
      cleft or high palate, dysmorphic features, and skeletal anomalies.
      Haploinsufficiency of PITX1, a transcription factor important for limb
      development, is likely the cause for the club feet, skeletal anomalies, and
      cleft/high palate, while additional genes, including SMAD5 and WNT8A, may also
      contribute to additional phenotypic features. Two patients with deletions also
      presented with corneal anomalies. To identify a causative gene for the corneal
      anomalies, we sequenced candidate genes in a family with apparent autosomal
      dominant keratoconus with suggestive linkage to 5q31, but no mutations in
      candidate genes were found. The duplications are smaller than the deletions, and
      the patients with duplications have nonspecific features. Although development is
      likely affected by increased dosage of the genes in the region, the developmental
      disruption appears less severe than that seen with deletion.

PMID- 21744491
TI  - Delineation of dermatan 4-O-sulfotransferase 1 deficient Ehlers-Danlos syndrome:
      observation of two additional patients and comprehensive review of 20 reported
      patients.
AB  - Loss-of-function mutations in CHST14, dermatan 4-O-sulfotransferase 1 (D4ST1)
      deficiency, have recently been found to cause adducted thumb-clubfoot syndrome
      (ATCS; OMIM#601776) and a new type of Ehlers-Danlos syndrome (EDS) coined as EDS
      Kosho Type (EDSKT) [Miyake et al., 2010], as well as a subset of kyphoscoliosis
      type EDS without lysyl hydroxylase deficiency (EDS VIB) coined as
      musculocontractural EDS (MCEDS) [Malfait et al., 2010]. Lack of detailed clinical
      information from later childhood to adulthood in ATCS and lack of detailed
      clinical information from birth to early childhood in EDSKT and MCEDS have made
      it difficult to determine whether these disorders would be distinct clinical
      entities or a single clinical entity with variable expressions and with different
      presentations depending on the patients' ages at diagnosis. We present detailed
      clinical findings and courses of two additional unrelated patients, aged 2 years
      and 6 years, with EDSKT with a comprehensive review of 20 reported patients with
      D4ST1 deficiency, which supports the notion that these disorders constitute a
      clinically recognizable form of EDS. The disorder, preferably termed D4ST1
      deficient EDS, is characterized by progressive multisystem fragility-related
      manifestations (joint dislocations and deformities, skin hyperextensibility,
      bruisability, and fragility; recurrent large subcutaneous hematomas, and other
      cardiac valvular, respiratory, gastrointestinal, and ophthalmological
      complications) resulting from impaired assembly of collagen fibrils, as well as
      various malformations (distinct craniofacial features, multiple congenital
      contractures, and congenital defects in cardiovascular, gastrointestinal, renal,
      ocular, and central nervous systems) resulting from inborn errors of development.

PMID- 21744492
TI  - X-linked mental retardation with alacrima and achalasia-Triple A syndrome or a
      new syndrome?
AB  - We describe a consanguineous Israeli Arab kindred with five males in two
      interrelated families with intellectual disabilities, alacrima, achalasia, and
      mild autonomic dysfunction. Adrenal function is normal. Their phenotype is
      similar to the phenotype observed in autosomal recessive Triple A syndrome except
      for the presence of mental retardation in all affected individuals. The pedigree
      is compatible with either X-linked or autosomal recessive inheritance. Sequencing
      of the AAAS gene causing autosomal recessive Triple A syndrome did not reveal
      mutations. Genotyping of affected family members identified a 16.4 Mb continuous
      segment of identical alleles shared by the patients between markers rs2748314 and
      rs5906782 on Xp11.23-p21, establishing linkage to chromosome X. This study
      further confirms genetic heterogeneity in Triple A syndrome and points to a
      clinically different subtype including significant cognitive impairment.

PMID- 21744493
TI  - Confocal backscattering spectroscopy for leukemic and normal blood cell
      discrimination.
AB  - Leukemia is the most common pediatric cancer and leading cause of cancer related
      deaths in children. Improvements in the assessment of leukemic cells have the
      potential to influence not only the diagnosis of leukemia, but also the risk
      assessment of patients during the course of the treatment, both of which are
      important for improving the cure rate for this disease. In this study, we report
      on the design and performance of a confocal laser based system built to collect
      backscattered light over a range of 26 degrees  at 405, 488, and 633 nm to
      discriminate leukemic cells from normal red blood cells (RBC) and white blood
      cells (WBC). The design of the system is based on the spectral differences
      observed from spectroscopy measurements with a similar system designed with a
      white light source. Significant differences are observed in the intensity and
      wavelength dependence of leukemic cells from normal RBC and WBC. Specifically,
      the distinct light scattering of RBC is due to hemoglobin absorption, allowing
      for its discrimination from leukemic cells, mononuclear, and polymorphonuclear
      WBC particularly at certain wavelengths. Meanwhile, the high scattering
      intensities of polymorphonuclear WBC reflect the intracellular complexity of
      these cells in comparison to the leukemic or normal lymphocytes. Additionally,
      the detected light scattering spectra for leukemic cells are consistently steeper
      in comparison to normal WBC, which we attributed to differences in the fractal
      organization of intracellular scatterers. Based on our findings, the system has
      potential applications in the detection and quantification of leukemic cells in
      blood either in vivo or in vitro, using microfluidic-based systems, for disease
      monitoring.

PMID- 21744494
TI  - Can new optical techniques for in vivo imaging and flow cytometry of the
      microcirculation benefit sickle cell disease research?
AB  - Intravital microscopy is a valuable tool for research into sickle cell disease
      with studies being carried out on transgenic mice and human volunteers. The
      method has helped to develop an explanation for sickle crises based on cell
      adhesion to the vascular endothelium followed by logjamming of rigid sickle cells
      and has stimulated much research into new treatments. In recent years there have
      been numerous new optical techniques developed for imaging the microcirculation
      and understanding the circulation of cells within the body, many of which have
      been further developed into in vivo flow cytometry techniques. This brief review
      highlights some of the progress made to date in the understanding of sickle cell
      disease using intravital microscopy. New techniques for imaging the
      microcirculation and their potential uses in understanding sickle cell disease
      are discussed.

PMID- 21744495
TI  - Temperature determination of resonantly excited plasmonic branched gold
      nanoparticles by X-ray absorption spectroscopy.
AB  - The fields of bioscience and nanomedicine demand precise thermometry for
      nanoparticle heat characterization down to the nanoscale regime. Since current
      methods often use indirect and less accurate techniques to determine the
      nanoparticle temperature, there is a pressing need for a direct and reliable
      element-specific method. In-situ extended X-ray absorption fine structure (EXAFS)
      spectroscopy is used to determine the thermo-optical properties of plasmonic
      branched gold nanoparticles upon resonant laser illumination. With EXAFS, the
      direct determination of the nanoparticle temperature increase upon laser
      illumination is possible via the thermal influence on the gold lattice
      parameters. More specifically, using the change of the Debye-Waller term
      representing the lattice disorder, the temperature increase is selectively
      measured within the plasmonic branched nanoparticles upon resonant laser
      illumination. In addition, the signal intensity shows that the nanoparticle
      concentration in the beam more than doubles during laser illumination, thereby
      demonstrating that photothermal heating is a dynamic process. A comparable
      temperature increase is measured in the nanoparticle suspension using a
      thermocouple. This good correspondence between the temperature at the level of
      the nanoparticle and at the level of the suspension points to an efficient heat
      transfer between the nanoparticle and the surrounding medium, thus confirming the
      potential of branched gold nanoparticles for hyperthermia applications. This work
      demonstrates that X-ray absorption spectroscopy-based nanothermometry could be a
      valuable tool in the fast-growing number of applications of plasmonic
      nanoparticles, particularly in life sciences and medicine. 

PMID- 21744496
TI  - Long-range nanoparticle surface-energy-transfer ruler for monitoring photothermal
      therapy response.
AB  - A recent gold nanotechnology-driven approach opens up a new possibility for the
      destruction of cancer cells through photothermal therapy. Ultimately,
      photothermal therapy may enter into clinical therapy and, as a result, there is
      an urgent need for techniques to monitor the tumor response to therapy. Driven by
      this need, a nanoparticle surface-energy-transfer (NSET) approach to monitor the
      photothermal therapy process by measuring a simple fluorescence intensity change
      is reported. The fluorescence intensity change is due to the light-controlled
      photothermal release of single-stranded DNA/RNA via dehybridization during the
      therapy process. Time-dependent results show that just by measuring the
      fluorescence intensity change, the photothermal therapy response during the
      therapy process can be monitored. The possible mechanism and operating principle
      of the NSET assay are discussed. Ultimately, this NSET assay could have enormous
      potential applications in rapid, on-site monitoring of the photothermal therapy
      process, which is critical to providing effective treatment of cancer and
      multidrug-resistant bacterial infections. 

PMID- 21744497
TI  - Genomic biomarkers in predictive medicine: an interim analysis.

PMID- 21744498
TI  - A serum circulating miRNA diagnostic test to identify asymptomatic high-risk
      individuals with early stage lung cancer.
AB  - Lung cancer is the first cause of cancer mortality worldwide, and its early
      detection is currently the main available strategy to improve disease prognosis.
      While early diagnosis can be successfully achieved through tomography-based
      population screenings in high-risk individuals, simple methodologies are needed
      for effective cancer prevention programs. We developed a test, based on the
      detection of 34 microRNAs (miRNAs) from serum, that could identify patients with
      early stage non-small cell lung carcinomas (NSCLCs) in a population of
      asymptomatic high-risk individuals with 80% accuracy. The signature could assign
      disease probability accurately either in asymptomatic or symptomatic patients, is
      able to distinguish between benign and malignant lesions, and to capture the
      onset of the malignant disease in individual patients over time. Thus, our test
      displays a number of features of clinical relevance that project its utility in
      programs for the early detection of NSCLC.

PMID- 21744499
TI  - Vitreoscilla hemoglobin expression in engineered Escherichia coli: improved
      performance in high cell-density batch cultivations.
AB  - High cell-density cultivations are the preferred system for biomolecules
      production by Escherichia coli. It has been previously demonstrated that a strain
      of E. coli with a modified substrate transport system is able to attain high cell
      densities in batch mode, due to the very low overflow metabolism displayed. The
      use of elevated amounts of glucose from the beginning of the cultivation,
      eliminates the existence of substrate gradients due to deficient mixing at large
      scale. However, the large amounts of oxygen demanded resulted in microaerobic
      conditions after some hours of cultivation, even at small-scale. In this work,
      the effect of expressing the Vitreoscilla hemoglobin (VHb) in the engineered
      strain during batch cultures using high-glucose concentrations was tested.
      Together, the expression of VHb and the modified substrate transport system
      resulted in a 33% increase of biomass production compared to the parental strain
      (W3110) lacking the VHb in batch cultivations using 25 g/L of glucose. When 50
      g/L of glucose were used, expression of VHb in the modified strain led to 11%
      higher biomass production compared to W3110. The VHb also increased the growth
      rates of the strains by about 30% in the aerobic phase and more than 200% in the
      microaerobic phase of batch cultivation.

PMID- 21744500
TI  - Simulation of dissolved CO(2) gradients in a scale-down system: a metabolic and
      transcriptional study of recombinant Escherichia coli.
AB  - Deficient mixing in industrial-scale bioreactors is an important concern as it
      results in a heterogeneous environment that may affect microbial cell physiology.
      Dissolved carbon dioxide (dCO(2) ) fluctuations, which can occur in large-scale
      bioreactors, were simulated for the first time and their effects were evaluated
      on Escherichia coli expressing recombinant green fluorescent protein (GFP). The
      dCO(2) gradients were simulated by continuously circulating the medium between
      two vessels of a scale-down system to mimic mean circulation times (t(c) ) of 50,
      170, and 375 s. Specific growth rate (MU) decreased by 11% and acetate
      concentration increased by 23% at the highest t(c) compared to reference
      cultures. An increase in the time needed for attaining maximum GFP concentration
      was also observed. The effect of dCO(2) fluctuations on the transcriptional
      levels of genes involved in the glutamate decarboxylase (gadA and gadC) and alpha
      ketoglutarate dehydrogenase (sucA and sucB) were analyzed by quantitative real
      time PCR. Such genes are known to be highly over- or underexpressed at elevated
      constant dCO(2) . Expression levels of gadA and gadC increased up to 60% and 72%,
      and sucA decreased 1.8-fold in the culture performed at the highest t(c) . Only a
      minor decrease of sucB expression was observed at t(c) of 170 and 375 s. Although
      exposure to continuous high dCO(2) can affect culture performance, in this work
      it was shown that E. coli is able to rescue its metabolism in very short times
      when cells are intermittently returned to low dCO(2) conditions after being
      exposed to high dCO(2) .

PMID- 21744501
TI  - Scale-down/scale-up studies leading to improved commercial beer fermentation.
AB  - Scale-up/scale-down techniques are vital for successful and safe commercial-scale
      bioprocess design and operation. An example is given in this review of recent
      studies related to beer production. Work at the bench scale shows that brewing
      yeast is not compromised by mechanical agitation up to 4.5 W/kg; and that
      compared with fermentations mixed by CO(2) evolution, agitation >= 0.04 W/kg is
      able to reduce fermentation time by about 20%. Work at the commercial scale in
      cylindroconical fermenters shows that, without mechanical agitation, most of the
      yeast sediments into the cone for about 50% of the fermentation time, leading to
      poor temperature control. Stirrer mixing overcomes these problems and leads to a
      similar reduction in batch time as the bench-scale tests and greatly reduces its
      variability, but is difficult to install in extant fermenters. The mixing
      characteristics of a new jet mixer, a rotary jet mixer, which overcomes these
      difficulties, are reported, based on pilot-scale studies. This change enables the
      advantages of stirring to be achieved at the commercial scale without the
      problems. In addition, more of the fermentable sugars are converted into ethanol.
      This review shows the effectiveness of scale-up/scale-down studies for improving
      commercial operations. Suggestions for further studies are made: one concerning
      the impact of homogenization on the removal of vicinal diketones and the other on
      the location of bubble formation at the commercial scale.

PMID- 21744502
TI  - Current progress of siRNA/shRNA therapeutics in clinical trials.
AB  - Through a mechanism known as RNA interference (RNAi), small interfering RNA
      (siRNA) molecules can target complementary mRNA strands for degradation, thus
      specifically inhibiting gene expression. The ability of siRNAs to inhibit gene
      expression offers a mechanism that can be exploited for novel therapeutics.
      Indeed, over the past decade, at least 21 siRNA therapeutics have been developed
      for more than a dozen diseases, including various cancers, viruses, and genetic
      disorders. Like other biological drugs, RNAi-based therapeutics often require a
      delivery vehicle to transport them to the targeted cells. Thus, the clinical
      advancement of numerous siRNA drugs has relied on the development of siRNA
      carriers, including biodegradable nanoparticles, lipids, bacteria, and attenuated
      viruses. Most therapies permit systemic delivery of the siRNA drug, while others
      use ex vivo delivery by autologous cell therapy. Advancements in bioengineering
      and nanotechnology have led to improved control of delivery and release of some
      siRNA therapeutics. Likewise, progress in molecular biology has allowed for
      improved design of the siRNA molecules. Here, we provide an overview of siRNA
      therapeutics in clinical trials, including their clinical progress, the
      challenges they have encountered, and the future they hold in the treatment of
      human diseases.

PMID- 21744503
TI  - Small mesoporous silica nanoparticles as carriers for enhanced photodynamic
      therapy.
AB  - Small mesoporous silica nanoparticles (MSNs; ca. 37 nm in diameter) have a high
      loading capacity for a hydrophobic photosensitizer, SiPcCl(2) (82.6% in weight),
      and excellent endocytosis properties. As a result, the amount of SiPcCl(2) being
      delivered to cancer cells is increased by approximately two orders of magnitude
      compared to pure SiPcCl(2) at the same dosage, and the photodynamic therapy (PDT)
      efficiency is enhanced by over fourfold. Our method can be widely used to
      increase the dosage of hydrophobic anti-cancer drugs in cancer cells and
      therefore increase the cytotoxicity of the drugs.

PMID- 21744504
TI  - Dynamic covalent chemistry: a facile room-temperature, reversible, Diels-Alder
      reaction between anthracene derivatives and N-phenyltriazolinedione.
AB  - A series of readily accessible, dynamic Diels-Alder reactions that are reversible
      at room temperature have been developed between anthracene derivatives as dienes
      and N-phenyl-1,2,4-triazoline-3,5-dione as the dienophile. The adducts formed
      undergo reversible component exchange to form dynamic libraries of equilibrating
      cycloadducts. Furthermore, reversible adduct formation allows temperature
      dependent modulation of the fluorescent properties of anthracene components; a
      feature of potential interest for the design of optodynamic polymeric materials
      by careful selection and manipulation of these simple dienes and dienophiles.

PMID- 21744505
TI  - Chemical modification and organelle-specific localization of orlistat-like
      natural-product-based probes.
AB  - Orlistat, also known as tetrahydrolipstatin (THL), is an FDA-approved anti
      obesity drug with potential anti-cancer activity. Previously, we developed a
      chemical proteomic approach, based on the Orlistat-like probe (1a) for large
      scale identification of unknown cellular targets of Orlistat in human
      hepatocytes. In this article, we report the chemical synthesis and biological
      evaluation of an expanded set of Orlistat-like compounds, with the intention to
      further dissect and manipulate potential cellular targets of Orlistat. In doing
      so, we carried out proteome-wide activity-based profiling and large-scale pull
      down/LCMS analysis of these compounds in live HepG2 cells, and successfully
      identified many putative cellular targets for Orlistat and its structural
      analogues. By qualitatively assessing the spectra counts of potential protein
      hits against each of the seventeen Orlistat analogues, we obtained both common
      and unique targets of these probes. Our results revealed that subtle structural
      modifications of Orlistat led to noticeable changes in both the cellular potency
      and target profiles of the drug. In order to further improve the cellular
      activity of Orlistat, we successfully applied the well-established AGT/SNAP-tag
      technology to our cell-permeable, benzylguanine (BG)-containing Orlistat variant
      (4). We showed that the drug could be delivered and effectively retained in
      different sub-cellular organelles of living cells. This strategy may provide a
      general and highly effective chemical tool for the potential sub-cellular
      targeting of small molecule drugs.

PMID- 21744506
TI  - Fe3O4 nanoparticles: a conveniently reusable catalyst for the reduction of
      nitroarenes using hydrazine hydrate.

PMID- 21744507
TI  - An efficient anthraquinone-resin hybrid co-catalyst for Fenton-like reactions:
      acceleration of the iron cycle using a quinone cycle under visible-light
      irradiation.

PMID- 21744508
TI  - A synthetic metabolic pathway for production of the platform chemical isobutyric
      acid.

PMID- 21744509
TI  - Biobutanol separation with the metal-organic framework ZIF-8.

PMID- 21744510
TI  - Human mesenchymal stem cell culture: rapid and efficient isolation and expansion
      in a defined serum-free medium.
AB  - Human mesenchymal stem cells (hMSCs) are typically obtained for research or
      therapeutic applications by isolating and subculturing adherent cells from bone
      marrow on tissue-culture substrates using growth media. The purity and properties
      of the resulting populations can be affected greatly by the conditions under
      which they are cultured. Fetal bovine serum (FBS), although ill-defined, has been
      widely used as a critical requirement for conventional hMSC culture. However, a
      defined serum-free medium would greatly facilitate the development of robust,
      clinically acceptable bioprocesses for reproducibly generating quality-assured
      cells. The present study provides evidence demonstrating that a defined serum
      free medium (PPRF-msc6) shows several beneficial features over a conventional FBS
      containing medium for the production of hMSCs. When compared to control FBS-based
      cultures, PPRF-msc6 medium supported the derivation of hMSCs from primary
      cultures of bone marrow cells in a more rapid and consistent manner. Furthermore,
      hMSCs cultured in PPRF-msc6 exhibited: (a) a greater colony-forming capacity in
      primary as well as passaged cultures; (b) negligible lag phase and explicit
      exponential growth; (c) lower population doubling times (21-26 h vs 35-38 h
      between passage levels 1 and 10); (d) a greater number of population doublings
      (62 +/- 4 vs 43 +/- 2; over a 2 month period); and (e) a higher degree of
      homogeneity in size. Our data demonstrate that PPRF-msc6 is an important
      development which opens the door for the rapid, efficient and reproducible
      production of hMSCs in clinical settings.

PMID- 21744511
TI  - Osteoblast growth and bone-healing response to three-dimensional poly(epsilon
      caprolactone fumarate) scaffolds.
AB  - Poly(epsilon-caprolactone fumarate) (PCLF) scaffold formulations were assessed as
      a delivery system for recombinant human bone morphogenetic protein (rhBMP-2) for
      bone tissue engineering. The formulations included PCLF with combinations of
      poly(vinyl alcohol) (PVA) and hydroxyapatite (HA). The assessments included in
      vitro and in vivo assays. In vitro assays validated cell attachment using a pre
      osteoblast cell line (MC3T3-E1). Additionally, in vitro release profiles of rhBMP
      2 from PCLF scaffolds were determined up to 21 days. The data suggested that PCLF
      incorporated with PVA and HA accelerated rhBMP-2 release and that the released
      protein was bioactive. For the in vivo study, a critical-sized defect (CSD) model
      in rabbit calvaria was used to test PCLF scaffolds. At 6 weeks post-implantation,
      significantly more bone formation was measured in PCLF scaffolds containing rhBMP
      2 than in scaffolds without rhBMP-2. In conclusion, we demonstrated that PCLF
      delivered biologically active rhBMP-2, promoted bone healing in a CSD and has
      potential as a bone tissue engineering scaffold.

PMID- 21744512
TI  - An analysis of the educational value of low-fidelity anatomy models as external
      representations.
AB  - Although high-fidelity digital models of human anatomy based on actual cross
      sectional images of the human body have been developed, reports on the use of
      physical models in anatomy teaching continue to appear. This article aims to
      examine the common features shared by these physical models and analyze their
      educational value based on the literature on cognition, learning, and external
      representations. A literature search on these physical models in three popular
      anatomy journals published over a 10-year period from 2001 to 2010 found that all
      of them have low fidelity: they oftentimes do not closely resemble the regions of
      the human body they are representing. They include only a small number of the
      structures that exist in these regions of the human body and do not accurately
      represent the shape and surface details of these structures. However, these
      models strongly correspond to the human body in the spatial relationship of the
      represented structures, which is crucial to achieving their educational purpose
      of teaching three-dimensional comprehension and anatomical reasoning. The
      educational value of these models includes acting as memory aids, reducing
      cognitive overload, facilitating problem solving, and arousing students'
      enthusiasm and participation. Because these models often lack a close resemblance
      to the human body, their use in anatomy teaching should always be accompanied by
      adequate explanations to the students to establish the correspondence between the
      models and the parts of the human body they are representing.

PMID- 21744513
TI  - Development of a rapid LC-MS/MS method for direct urinalysis of designer drugs.
AB  - The current immunoassay screening methodologies used to detect sympathomimetic
      amines within the context of workplace drug testing may fail to detect a number
      of the emerging designer drugs, for example beta-keto amphetamines and piperazine
      derivatives, commonly referred to as 'legal highs'. Therefore, a rapid multi
      analyte qualitative screening method, using ultra-high-pressure liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), was investigated for analysis
      of new designer drugs that have emerged from the former legal highs market. Eight
      analytes were targeted as model compounds: 4-methylmethcathinone (mephedrone),
      3,4-methylenedioxymethcathinone (bk-MDMA, 'methylone'), 2-methylamino-1-(3,4
      methylenedioxyphenyl)butan-1-one (bk-MBDB, 'butylone'), 4-methoxymethcathinone
      (bk-PMMA, 'methedrone'), 1-benzylpiperazine (BZP), 1-(3-trifluoromethyl phenyl)
      piperazine (TFMPP), 1-(3-chloro phenyl)-piperazine (mCPP), and 3, 4
      methylenedioxypyrovalerone (MDPV). The LC-MS/MS method developed encompassed
      direct analysis following a 1:4 dilution of urine with mobile phase to reduce
      matrix effects. Although not all compounds were completely resolved
      chromatographically, two product ions conferred sufficient specificity to allow
      target analyte identification. Although all target analytes were readily detected
      at 500 ng/ml, a cut-off of 1000 ng/ml was chosen to mirror the amphetamine
      screening cut-off commonly used for routine analysis of workplace drug testing
      samples. In conclusion, direct analysis using LC-MS/MS offers an attractive way
      forward for the development of a rapid routine screen for new psychoactive
      substances, particularly given the growing number of novel compounds.

PMID- 21744514
TI  - Current awareness of piperazines: pharmacology and toxicology.
AB  - Although many piperazine derivatives exist, only a limited number have been
      studied, whereby they have been found to be generally stimulant in nature
      resulting from dopaminergic, noradrenergic, and predominantly serotoninergic
      effects in the brain. Reported toxic effects include agitation, anxiety, cardiac
      symptoms (e.g. tachycardia) and sometimes seizures. As for many drugs, they are
      primarily metabolized by cytochrome P450 with subsequent possible glucuronidation
      and/or sulfation. Their abuse has been relatively recently observed in the last
      decade with only a few identified in biological fluid (primarily 1
      benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (3-TFMPP))
      despite publications of a number of analytical methods. Even when detected,
      however, the toxicological significance of their presence is often difficult to
      ascertain as many cases involve other drugs as well as a wide and overlapping
      range of concentrations found in blood (both in life and after death). This paper
      reviews the current pharmacological and toxicological information for piperazine
      derivatives and also includes new ante-mortem and post-mortem blood data.

PMID- 21744515
TI  - Social, policy, and public health perspectives on new psychoactive substances.
AB  - New psychoactive substances pose a particular challenge to those formulating
      drugs policy and related public health responses. This paper outlines some of the
      main issues arising from their use, with a particular focus on user perspectives.
      Such substances are often (at least initially) produced and distributed for
      different reasons than controlled drugs. They emerge in users' repertoires
      undetected by most monitoring systems and general population drug surveys. While
      reasons for use by innovators and early adopters are often in the spirit of self
      experimentation, such substances may rapidly diffuse to the recreational arena as
      a result of enthusiastic user propagation where they act as substitutes or
      complements to controlled drugs. The majority of substances are believed to be
      sourced, albeit not exclusively, from manufacturers based in China. They are
      retailed to consumers through the Internet and physical shops (such as 'head' and
      'smart' shops), as well as traditional 'street dealers' (although data on the
      significance of this latter route of supply are limited). The data required for
      risk assessment of the harms such substances may pose, as well as information
      required for accurate user-derived harm reduction advice, are often limited.
      Moreover, some involved in the commercial supply have deliberately misbranded
      products, including substituting the active substance, in apparent attempts to
      circumvent regulatory frameworks. This leaves users susceptible to both health
      and criminal justice harms. Despite various attempts to restrict the supply, they
      often continue to be available through the illicit market, although it is not yet
      possible to predict whether they will join other drugs such as MDMA and LSD as
      mainstays of the recreational pharmacopeia.

PMID- 21744516
TI  - Reference materials for new psychoactive substances.
AB  - Historically, the appearance of new psychoactive materials (and hence the
      requirement for new reference standards) has been relatively slow. This position
      has now changed, with 101 new psychoactive substances reported to EMCDDA-Europol
      since 2006. The newly reported materials, and associated metabolites, require
      properly certified reference materials to permit reliable identification and
      quantification. The traditional approach and timescales of reference material
      production and certification are being increasingly challenged by the appearance
      of these new substances. Reference material suppliers have to adopt new
      strategies to meet the needs of laboratories. This situation is particularly
      challenging for toxicology standards as the metabolism of many of these
      substances is initially unknown. Reference material production often involves
      synthesis from first principles. While it is possible to synthesis these
      materials, there can be significant difficulties, from synthetic complexities
      through to the need to use controlled materials. These issues are examined
      through a discussion of the synthesis of cathinones. Use of alternative sources,
      including pharmaceutical impurity materials or internet sourced products, as
      starting materials for conversion into appropriately certified reference
      materials are also discussed. The sudden appearance and sometimes brief lifetime
      in the market place of many of these novel legal highs or research chemicals
      present commercial difficulties for reference material producers. The need for
      collaboration at all levels is highlighted as essential to rapid identification
      of requirements for new reference materials. National or international
      commissioning or support may also be required to permit reference material
      producers to recover their development costs.

PMID- 21744517
TI  - Simultaneous chronic myeloid leukemia and chronic lymphocytic leukemia.

PMID- 21744518
TI  - Sing, muse: songs in Homer and in hospital.
AB  - This paper progresses the original argument of Richard Ratzan that formal
      presentation of the medical case history follows a Homeric oral-formulaic
      tradition.The everyday work routines of doctors involve a ritual poetics, where
      the language of recounting the patient's 'history' offers an explicitly aesthetic
      enactment or performance that can be appreciated and given meaning within the
      historical tradition of Homeric oral poetry and the modernist aesthetic of
      Minimalism. This ritual poetics shows a reliance on traditional word usages that
      crucially act as tools for memorisation and performance and can be linked to
      forms of clinical reasoning; both contain a tension between the oral and the
      written record, questioning the priority of the latter; and the performance of
      both helps to create the Janus-faced identity of the doctor as a 'performance
      artist' or 'medical bard' in identifying with medical culture and maintaining a
      positive difference from the patient as audience, offering a valid form of
      patient-centredness.

PMID- 21744519
TI  - The return from mania: a patient's journey.

PMID- 21744520
TI  - When staff speak up on safety, do managers listen--and act?

PMID- 21744521
TI  - [Erratum to: Propofol administration systems. Handling, hemodynamics and propofol
      consumption].

PMID- 21744522
TI  - Complementary medicine.

PMID- 21744523
TI  - Hospital in the home.

PMID- 21744524
TI  - Appointments on time.

PMID- 21744525
TI  - Hepatitis A.

PMID- 21744526
TI  - NY reports first HIV spread from live organ donor.

PMID- 21744527
TI  - Nursing ethos post-quake.

PMID- 21744528
TI  - Don't stifle experienced ENs.

PMID- 21744529
TI  - Continue debate on voluntary euthanasia.

PMID- 21744530
TI  - Correction. Homelessness is everyone's business.

PMID- 21744531
TI  - Another way.

PMID- 21744532
TI  - Prevention: a helpful addition to our health toolkit.

PMID- 21744533
TI  - [Images of nursing mothers in France, 18th and 19th centuries].
AB  - As they became more widely adopted in eighteenth- and nineteenth-century France,
      wet-nursing and wet-nurses appeared prominently in the iconography of the time.
      Such images turned negative as criticism against "mercenary breast-feeding"
      mounted. Over the nineteenth century in particular, wet-nurses were heavily
      featured in press caricatures: they were being mocked while described as simple
      minded, dumb, greedy creatures, with proclivities ranging from a taste for garish
      attire, to sexual appetites fuelling trysts in public gardens with soldiers on
      leave. A representative sample of such images will be selected to highlight the
      codes and values underpinning this mockery.

PMID- 21744534
TI  - [Disguises, invisibility and disqualification of the guards of children in French
      speaking Switzerland].
AB  - Various factors oblige today's parents to entrust their children to a child-care
      worker (CCW), providing services in the domestic sphere, either at the child's
      parental house or at the day-care worker's (DCW's) own home. Taking this into
      account, this paper examines job offers and applications for DCWs published in a
      regional Swiss newspaper as well as other job offers and applications published
      on a website called bestnounou.ch. The parents often tend to use a variety of
      terms, which do not point to the child-caring or rearing activity itself, but
      rather emphasise sociological characteristics of the CCW (age, gender, civil
      status), requesting, for example, a "lady", a "grandmother", a "student".
      Thereby, the parents present the child-care work as: (1) a secondary and
      temporary activity in relation to another major stable activity (motherhood,
      apprenticeship, retirement); and (2) an activity that does not require
      professional skills but inborn aptitudes. Moreover, employers use as synonyms
      distinctive terms, which refer to various categories of CCW and domestic workers,
      whose schedules of conditions and salaries are regulated and differ. The parents'
      inclination to use terms designating the most precarious and underpaid CCW
      underscores the importance of child-care in the domestic sphere. It leads also to
      a public image of child-care workers as being a fragmented, unstable, little
      qualified and economically inconsistent workforce, in contrast to the stable and
      structural need for their specific services, allowing parents to face their
      familial and professional responsibilities.

PMID- 21744535
TI  - [Take care of a child, one work like any other?].
AB  - This article has its roots in the basic contradictions, which go back to the
      eighteenth and nineteenth centuries, between the self-interest and the care of
      others, exemplified by the delegation of responsibility for the care of children
      and other vulnerable persons. This splitting of human life-supporting activities
      has sealed women's dependence on men by setting off the lucrative area from the
      private, non-lucrative sphere of activities. These contradictions become
      paradoxical as soon as we consider the delegation of responsibility for the care
      of a child to someone not related to the child. This article addresses the
      question of how the child's developmental needs can be met without damage to
      his/her sensitivity, and his/her perception of others or of the cooperation
      involved. As soon as it is born, the child, a thoroughly interactive being,
      discerns the relationships it entertains with those who are in charge of him/her.
      The persons - mostly women - who take care of the child are not interchangeable,
      since they bring their own subjectivity into their dealings with the child and
      this is reciprocal. The women's skills, frequently thought to be "undefinable",
      but which many women, whether related or not to the child, have developed or
      should develop, are brought into play and are either transmitted or acquired in
      the course of their care of the child; these skills are not by nature "feminine
      skills", but they require a great deal of reactivity and sensitivity and
      therefore, many child professionals, mothers' aids and children's care-takers in
      the home are hurt and insulted by the low esteem in which they are held. These
      skills and human qualities, which are the result of feelings more than of
      formalised knowledge, techniques or theories - albeit these are also necessary -
      make child care and child rearing an art. These skills seem to be in total
      contradiction with those that are current in the world of labour, where the tempo
      of work, flexibility of working hours, the evaluation criteria and anxiety are
      conditioned by economic considerations and rest on purely monetary factors.
      Finally, a recognition of these sensitive qualities - when it is given - must of
      necessity be inter-subjective but also be societal. The latter requires a new,
      different organisation of the labour world, one which recognises the diversity of
      human activities, where each can find a sense of social usefulness by
      contributing to the satisfaction of others' social needs and having one's own
      needs satisfied by others - by many others. This would presuppose reversing the
      meaning of the division of labour and of life-maintaining activities by placing
      greater emphasis on "interest in others".

PMID- 21744536
TI  - [Greek nannies in Rome?].
AB  - In Roman society, parents often entrusted their newborn to a wet nurse, usually a
      slave or a lower-class freeborn woman, who normally lived with them. It was
      advised to choose with care the right person, as milk is not a neutral bodily
      substance but transmits many properties, physical and moral. Soranus devotes an
      entire chapter to the meticulous inspection of the nurse's milk and temper. The
      nurse's character must be checked as thoroughly as her physical health. The mind
      of the newborn, compared with wax, is from the start and forever impressed
      positively or negatively. Mnesitheus and others even advise choosing a woman
      resembling physically the mother, or a handsome person; Favorinus and others
      reject violently the recourse to wet nursing as immoral; submitting the child to
      the pernicious influence of a foreign non-kin person implies the destruction of
      family ties. Wet nurses had to follow a specific diet and to accept giving up
      their sexual life, which would corrupt the milk in case of a new pregnancy. Roman
      upper-class families attributed different qualities to nurses according to their
      ethnic origin: Egyptians were allegedly fond of children, Thracians robust and
      devoted, Spartans tough. The best were the Greeks, because they would teach Greek
      language - and culture - to their nurslings. The nurse's social function was
      extensive. Her role did not stop at the weaning period. Much evidence shows that
      she was a lifelong companion. In positive circumstances, she could construct non
      kin relationships and became, through connections not of blood but of milk, a
      member of an extended family. Funerary inscriptions and literary sources show
      that some nurses were rewarded by freedom. Breast-feeding also created milk-ties
      between the nurslings, who could gain social elevation thanks to this bonding.

PMID- 21744537
TI  - Inoculators, the Indigenous obstacle to vaccination in colonial Burma.

PMID- 21744538
TI  - Syphilis and the Kachin regeneration campaign, 1937-1938.

PMID- 21744539
TI  - Healing, rebellion, and the law: ethnologies of medicine in colonial Burma, 1928
      1932.

PMID- 21744540
TI  - The alchemist and his ball.

PMID- 21744541
TI  - Urbanisation, poverty and sexual behaviour: the tale of five African cities.
AB  - The question of how urbanisation and poverty are linked in sub-Saharan Africa is
      an increasingly pressing one. The urban character of the HIV epidemic in sub
      Saharan Africa exacerbates concern about the urbanisation - poverty relationship.
      Recent empirical work has linked urban poverty, and particularly slum residence,
      to risky sexual behaviour in Kenya's capital city, Nairobi. This paper explores
      the generalisability of these assertions about the relationship between urban
      poverty and sexual behaviour using Demographic and Health Survey data from five
      African cities: Accra (Ghana), Dar-es-Salaam (Tanzania), Harare (Zimbabwe),
      Kampala (Uganda) and Nairobi (Kenya). The study affirms that, although risky
      behaviour varies across the five cities, slum residents demonstrate riskier
      sexual behaviour compared with non-slum residents. There is earlier sexual debut,
      lower condom usage and more multiple sexual partners among women residing in slum
      households regardless of setting, suggesting a relatively uniform effect of urban
      poverty on sexual risk behaviour.

PMID- 21744542
TI  - Clerical "concubines" in northern Italy during the fourteenth century.
AB  - This essay reconstructs the lives of a neglected group of women in the Christian
      church during the later Middle Ages. So-called clerical "concubines" were well
      known in their communities, but their lived experience has been largely ignored
      by modern historians. Yet studying clerical concubines sheds light not only on
      the women themselves, but also on the social organization of the medieval
      Christian church. Drawing on information gathered from notarial acts across the
      northern Italian peninsula, I argue that concubines were not a unitary group.
      Their experiences varied instead according to their status and the regions they
      inhabited. For instance, while laywomen who became priests' concubines moved into
      their lovers' homes, nuns retained cells in their religious houses during these
      relationships. Furthermore, concubines in cities such as Treviso could openly
      live with their lovers and share their property, while in other places, such as
      Bergamo, severe legal restrictions on concubines made them a particularly
      vulnerable group.

PMID- 21744543
TI  - Patients of the state: an ethnographic account of poor people's waiting.
AB  - Drawing on six months of ethnographic fieldwork in the main welfare office of the
      city of Buenos Aires, this article dissects poor people's lived experiences of
      waiting. The article examines the welfare office as a site of intense sociability
      amidst pervasive uncertainty. Poor people's waiting experiences persuade the
      destitute of the need to be patient, thus conveying the implicit state request to
      be compliant clients. An analysis of the sociocultural dynamics of waiting helps
      us understand how (and why) welfare clients become not citizens but patients of
      the state.

PMID- 21744544
TI  - Living under a democracy: participation and its impact on the living conditions
      of the poor.
AB  - The Brazilian democratization took place between 1985 and 1988. In 1985, the
      authoritarian power holders transferred political power to civilians, and in
      1988, a new democratic constitution was enacted, thus finalizing the transition.
      The end of the transition triggered processes of participation in different
      Brazilian cities, such as Sao Paulo, Belo Horizonte, Recife, and Rio de Janeiro.
      However, only in Porto Alegre could the political context in the
      postdemocratization period generate a process of reverting priorities, that is to
      say, of inverting the pattern of democratic participation and the pattern of
      public investment at the urban level. In this article, I show the social
      conditions of the poor in the city of Porto Alegre in 1985, explain the emergence
      of participatory budgeting in the city, and show how democracy made a difference
      in the living conditions of the urban poor in the city of Porto Alegre. In the
      second part of the article, I analyze the recent expansion of participatory
      budgeting in Brazil and its recent expansion to midsize cities. In the final part
      of the article, I show how new participatory institutions are being introduced at
      the federal level of government. Participation at the local and national levels
      is making a difference in the living conditions of the Brazilian poor.

PMID- 21744545
TI  - Widows' land security in the era of HIV/AIDS: panel survey evidence from Zambia.
AB  - In areas of Africa hard hit by HIV/AIDS, there are growing concerns that many
      women lose access to land after the death of their husbands. However, there
      remains a dearth of quantitative evidence on the proportion of widows who lose
      access to their deceased husband's land, whether they lose all or part of that
      land, and whether there are factors specific to the widow, her family, or the
      broader community that influence her ability to maintain rights to land. This
      study examines these issues using average treatment effects models with
      propensity score matching applied to a nationally representative panel data of
      5,342 rural households surveyed in 2001 and 2004. Results are highly variable,
      with roughly a third of households incurring the death of a male household head
      controlling less than 50% of the land they had prior to their husband's death,
      while over a quarter actually controlled as much or even more land than while
      their husbands were alive. Widows who were in relatively wealthy households prior
      to their husband's death lose proportionately more land than widows in households
      that were relatively poor. Older widows and widows related to the local headman
      enjoy greater land security. Women in matrilineal inheritance areas were no less
      likely to lose land than women in patrilineal areas.

PMID- 21744546
TI  - The effect of early interventions in health and nutrition on on-time school
      enrollment: evidence from the Oportunidades Program in rural Mexico.
AB  - This article assesses whether early intervention to improve children's health and
      nutrition increases the probability of enrolling in primary school on time. Using
      experimental data from the Mexican conditional cash transfer (CCT) program,
      Oportunidades, a cross-sectional double-difference estimator on observations from
      two age cohorts of children is used to identify the impact of early intervention.
      The results indicate that early health and nutrition interventions can have a
      positive impact on the timing of enrollment and that caregiver characteristics
      affect the magnitude of the impact. Early intervention also appears to decrease
      days of school missed. Overall the results indicate that the full impact of CCT
      programs on education cannot be measured in the short run as benefits of early
      health and nutrition interventions may be also felt in the distant future.

PMID- 21744547
TI  - Child fostering chains among Ovambo families in Namibia, Southern Africa.
AB  - Childcare across sub-Saharan Africa is often socially distributed among adults,
      with care by the biological mother being one of several options available for
      children. Children typically move within and outside of large extended kin
      networks. Based on an ethnographic study of four Ovambo families in Namibia, this
      article seeks to understand the cultural logic of fostering. Several themes that
      emerged from the study are discussed here, including the varied motivations of
      fostering, the cultural scripts of equality, and the rules of reciprocity in
      exchange, which are involved. Education shapes a mother's choices of care-giving
      and creates both a supply of children and a demand on households. The
      implications for HIV/AIDS orphans are discussed.

PMID- 21744549
TI  - [Improve the prescription support].

PMID- 21744548
TI  - Differentiated childhoods: impacts of rural labor migration on left-behind
      children in China.
AB  - This article draws on data from research that includes 400 children who lived
      separately from their migrant parents in 10 rural communities in China, to
      explore the deep impacts of rural parents' migration on the care-giving and
      nurturing of children left behind. It shows that parent migration has brought
      about multiple impacts, mostly negative, on the lives of children, such as
      increased workloads, little study tutoring and supervision, and above all the
      unmet needs of parental affection. Children's basic daily care and personal
      safety could become problematic since surrogate caregivers, mostly elderly, are
      usually exhausted with livelihood maintenance. With illumination on the family
      dysfunction in children's development due to migration-induced family separation,
      this article highlights the social cost to rural families of parental migration.
      Urbanization in developing countries is obtained at the expense of rural migrants
      and their families, especially children left behind. Further attention is
      required to improve left-behind children's well being within split family
      structures and interregional migration.

PMID- 21744550
TI  - [Cleaning and surface disinfection as measure of good hygiene: observations from
      a hospital bed].

PMID- 21744551
TI  - [National quality registries. Protect or sell out the patients' integrity?].

PMID- 21744552
TI  - [Screening for cervix cancer can be more effective. Many lives can be saved if
      risk patients are included].

PMID- 21744553
TI  - [New guidelines for prevention of cervix cancer. ARG report on investigation and
      treatment of abnormal cytological smears].

PMID- 21744554
TI  - [Deactivation of implantable defibrillators--also an ethical issue. Written
      routines of the process are necessary as illustrated by the described case
      report].

PMID- 21744555
TI  - [News in cardiovascular genetics open for new therapeutic possibilities].

PMID- 21744556
TI  - [Popliteal entrapment--a rare condition that mostly affect youngsters. Cases
      among siblings suggest possible heredity].

PMID- 21744557
TI  - [Difficult choice between clarithromycin and metronidazole in polyneuropathy].

PMID- 21744558
TI  - [Norspan depot patch more and more common but its role in the treatment is
      difficult to assess].

PMID- 21744559
TI  - [There is difference between humanitarian and military medical aid].

PMID- 21744560
TI  - [Social physicians--between health care and social service].

PMID- 21744561
TI  - [Radiation tsunami].

PMID- 21744562
TI  - [With heart defect into career].

PMID- 21744563
TI  - [Fetal surgery exemplified by spina bifida aperta].

PMID- 21744564
TI  - [How does a man deal with a life threatening illness?].

PMID- 21744565
TI  - [Generalization of nursing education is rejected. Committee for observing the
      needs of children].

PMID- 21744566
TI  - [Child protection and early support: use of family, health and pediatric
      nursing].

PMID- 21744567
TI  - [How does a mother with an ADHD child experience her situation? (I)].

PMID- 21744568
TI  - ["My child frequently twists his head...!" Sandifer syndrome - not just a rare
      occurrence].

PMID- 21744569
TI  - [Safe management of injections and parenteral infusions: recommendations of a new
      American guideline are not transferable to Germany].

PMID- 21744570
TI  - [Multiplicity of children's time perception].

PMID- 21744571
TI  - [Exanthema subitum - 3 day fever - HHV 6 infection - roseola infantum - 6th
      disease].